PMID- 16081004
TI  - Regulation of the timing of MNTB neurons by short-term and long-term modulation
      of potassium channels.
AB  - The firing patterns of neurons in central auditory pathways encode specific
      features of sound stimuli, such as frequency, intensity and localization in
      space. The generation of the appropriate pattern depends, to a major extent, on
      the properties of the voltage-dependent potassium channels in these neurons. The
      mammalian auditory pathways that compute the direction of a sound source are
      located in the brainstem and include the connection from bushy cells in the
      anteroventral cochlear nucleus (AVCN) to the principal neurons of the medial
      nucleus of the trapezoid body (MNTB). To preserve the fidelity of timing of
      action potentials that is required for sound localization, these neurons express
      several types of potassium channels, including the Kv3 and Kv1 families of
      voltage-dependent channels and the Slick and Slack sodium-dependent channels.
      These channels determine the pattern of action potentials and the amount of
      neurotransmitter released during repeated stimulation. The amplitude of currents
      carried by one of these channels, the Kv3.1b channel, is regulated in the short
      term by protein phosphorylation, and in the long term, by changes in gene
      expression, such that the intrinsic excitability of the neurons is constantly
      being regulated by the ambient auditory environment.

PMID- 16081005
TI  - Spectral integration in auditory cortex: mechanisms and modulation.
AB  - Auditory cortex contributes to the processing and perception of spectrotemporally
      complex stimuli. However, the mechanisms by which this is accomplished are not
      well understood. In this review, we examine evidence that single cortical neurons
      receive input covering much of the audible spectrum. We then propose an
      anatomical framework by which spectral information converges on single neurons in
      primary auditory cortex, via a combination of thalamocortical and intracortical
      "horizontal" pathways. By its nature, the framework confers sensitivity to
      specific, spectrotemporally complex stimuli. Finally, to address how spectral
      integration can be regulated, we show how one neuromodulator, acetylcholine,
      could act within the hypothesized framework to alter integration in single
      neurons. The results of these studies promote a cellular understanding of
      information processing in auditory cortex.

PMID- 16081006
TI  - Active listening: task-dependent plasticity of spectrotemporal receptive fields
      in primary auditory cortex.
AB  - Listening is an active process in which attentive focus on salient acoustic
      features in auditory tasks can influence receptive field properties of cortical
      neurons. Recent studies showing rapid task-related changes in neuronal
      spectrotemporal receptive fields (STRFs) in primary auditory cortex of the
      behaving ferret are reviewed in the context of current research on cortical
      plasticity. Ferrets were trained on spectral tasks, including tone detection and
      two-tone discrimination, and on temporal tasks, including gap detection and click
      rate discrimination. STRF changes could be measured on-line during task
      performance and occurred within minutes of task onset. During spectral tasks,
      there were specific spectral changes (enhanced response to tonal target frequency
      in tone detection and discrimination, suppressed response to tonal reference
      frequency in tone discrimination). However, only in the temporal tasks, the STRF
      was changed along the temporal dimension by sharpening temporal dynamics. In
      ferrets trained on multiple tasks, distinctive and task-specific STRF changes
      could be observed in the same cortical neurons in successive behavioral sessions.
      These results suggest that rapid task-related plasticity is an ongoing process
      that occurs at a network and single unit level as the animal switches between
      different tasks and dynamically adapts cortical STRFs in response to changing
      acoustic demands.

PMID- 16081007
TI  - Responses to species-specific vocalizations in the auditory cortex of awake and
      anesthetized guinea pigs.
AB  - Species-specific vocalizations represent an important acoustical signal that must
      be decoded in the auditory system of the listener. We were interested in
      examining to what extent anesthesia may change the process of signal decoding in
      neurons of the auditory cortex in the guinea pig. With this aim, the multiple
      unit activity, either spontaneous or acoustically evoked, was recorded in the
      auditory cortex of guinea pigs, at first in the awake state and then after the
      injection of anesthetics (33 mg/kg ketamine with 6.6 mg/kg xylazine). Acoustical
      stimuli, presented in free-field conditions, consisted of four typical guinea pig
      calls (purr, chutter, chirp and whistle), a time-reversed version of the whistle
      and a broad-band noise burst. The administration of anesthesia typically resulted
      in a decrease in the level of spontaneous activity and in changes in the strength
      of the neuronal response to acoustical stimuli. The effect of anesthesia was
      mostly, but not exclusively, suppressive. Diversity in the effects of anesthesia
      led in some recordings to an enhanced response to one call accompanied by a
      suppressed response to another call. The temporal pattern of the response to
      vocalizations was changed in some cases under anesthesia, which may indicate a
      change in the synaptic input of the recorded neurons. In summary, our results
      suggest that anesthesia must be considered as an important factor when
      investigating the processing of complex sounds such as species-specific
      vocalizations in the auditory cortex.

PMID- 16081008
TI  - Reconnecting neuronal networks in the auditory brainstem following unilateral
      deafening.
AB  - When we disturbed the auditory input of the adult rat by cochleotomy or noise
      trauma on one side, several substantial anatomical, cellular, and molecular
      changes took place in the auditory brainstem. We found that: (1) cochleotomy or
      severe noise trauma both lead to a considerable increase of immunoreactivity of
      the growth-associated protein GAP-43 in the ventral cochlear nucleus (VCN) of the
      affected side; (2) the expression of GAP-43 in VCN is restricted to presynaptic
      endings and short fiber segments; (3) axon collaterals of the cholinergic medial
      olivocochlear (MOC) neurons are the path along which GAP-43 reaches VCN; (4)
      partial cochlear lesions induce the emergence of GAP-43 positive presynaptic
      endings only in regions tonotopically corresponding to the extent of the lesion;
      (5) judging from the presence of immature fibers and growth cones in VCN on the
      deafened side, at least part of the GAP-43 positive presynaptic endings appear to
      be newly formed neuronal contacts following axonal sprouting while others may be
      modified pre-existing contacts; and (6) GAP-43 positive synapses are formed only
      on specific postsynaptic profiles, i.e., glutamatergic, glycinergic and
      calretinin containing cell bodies, but not GABAergic cell bodies. We conclude
      that unilateral deafening, be it partial or total, induces complex patterns of
      reconnecting neurons in the adult auditory brainstem, and we evaluate the
      possibility that the deafness-induced chain of events is optimized to remedy the
      loss of a bilaterally balanced activity in the auditory brainstem.

PMID- 16081009
TI  - Tinnitus as a plastic phenomenon and its possible neural underpinnings in the
      dorsal cochlear nucleus.
AB  - Tinnitus displays many features suggestive of plastic changes in the nervous
      system. These can be categorized based on the types of manipulations that induce
      them. We have categorized the various forms of plasticity that characterize
      tinnitus and searched for their neural underpinnings in the dorsal cochlear
      nucleus (DCN). This structure has been implicated as a possible site for the
      generation of tinnitus-producing signals owing to its tendency to become
      hyperactive following exposure to tinnitus inducing agents such as intense sound
      and cisplatin. In this paper, we review the many forms of plasticity that have
      been uncovered in anatomical, physiological and neurochemical studies of the DCN.
      Some of these plastic changes have been observed as consequences of peripheral
      injury or as fluctuations in the behavior and chemical activities of DCN neurons,
      while others can be induced by stimulation of auditory or even non-auditory
      structures. We show that many parallels can be drawn between the various forms of
      plasticity displayed by tinnitus and the various forms of neural plasticity which
      have been defined in the DCN. These parallels lend further support to the
      hypothesis that the DCN is an important site for the generation and modulation of
      tinnitus-producing signals.

PMID- 16081010
TI  - The effect of dorsal cochlear nucleus ablation on tinnitus in rats.
AB  - A growing body of evidence implies that the dorsal cochlear nucleus (DCN) plays
      an important role in tinnitus. To test the hypothesis that the rostral output of
      the DCN is necessary for the experience of chronic tinnitus, the dorsal DCN and
      the dorsal acoustic stria of rats with psychophysical evidence of tinnitus was
      ablated. If the DCN plays a necessary role in the generation of chronic tinnitus,
      ablating the DCN should decrease the evidence of tinnitus in subjects previously
      shown to have tinnitus. Contrary to prediction, bilateral dorsal DCN ablation did
      not significantly (n=11, p=0.707) affect the psychophysical evidence of tinnitus,
      and ipsilateral dorsal DCN ablation appeared to increase the evidence of tinnitus
      (n=9, p=0.018) compared to pre-ablation performance. It was concluded that the
      DCN does not act as a simple feed-forward source of chronic tinnitus. Alternative
      hypotheses were considered, among them that elevated DCN activity following
      acoustic trauma triggers persistent pathological changes distributed across more
      than one level of the auditory system. In addition to serving as a trigger, the
      DCN may also modify the experience of tinnitus, since the evidence of tinnitus
      was enhanced by ipsilateral DCN ablation.

PMID- 16081012
TI  - The anatomy of the calcaneus and surrounding structures.
AB  - Appreciation of the normal anatomy of the calcaneus is significant for various
      reasons. Restoration of normal anatomy has been of particular interest for
      fracture care. In addition, knowledge of surrounding structures is important when
      planning surgical approaches and vital when performing percutaneous procedures.
      Understanding of anatomic relationships allows discernment of the pathophysiology
      that is related to chronic conditions. The biomechanics of normal structures
      provides a theoretic basis for reconstruction and rehabilitation, and individual
      variations in calcaneal anatomy can be a predisposition for pathology.

PMID- 16081013
TI  - Mechanics of the subtalar joint and its function during walking.
AB  - Knowledge of the location of the subtalar joint axis in individual patients would
      permit clinical assessment of the forces and moments that produce frontal-plane
      foot and ankle deformities. Biomechanical analysis of the subtalar joint is
      hindered, however, by the inaccessibility of the talus, which makes locating the
      joint axis difficult, and by the high degree of intersubject anatomic variation.
      This article discusses work done with cadaver specimens and using invasive
      methods in vivo that has enhanced our understanding of the mechanics of the
      subtalar joint and its function during gait. Also reviewed are investigations of
      the actions of muscles that cross the subtalar joint.

PMID- 16081014
TI  - Imaging of the calcaneus.
AB  - The anatomy of the calcaneus is complex with multiple processes and grooves for
      support of related bony and soft tissue structures. With respect to imaging, the
      calcaneus and its articulations are a diagnostic challenge to radiologists and
      clinicians. This article focuses on the use of commonly employed radiologic
      modalities with respect to the anatomy of the calcaneus and some of the more
      common and challenging conditions that affect the calcaneus.

PMID- 16081015
TI  - Calcaneus fractures: a review article.
AB  - Calcaneus fractures are a significant burden to society. Assessment and treatment
      of these injuries has improved significantly. The use of CT scanning has allowed
      a greater understanding of the pathologic anatomy of these fractures, and has
      provided for prognostic classification systems with respect to outcome. The
      treatment options are diverse and are reviewed.

PMID- 16081016
TI  - Open calcaneal fractures: assessment and management.
AB  - Open calcaneal fractures are obscure fractures. Typically, these injuries result
      in a high-energy, polytraumatized patient population. Initial management consists
      of irrigation and debridement. Secondary forms of management continue to evolve.
      High-energy fracture subtypes and severe soft tissue injuries portend an
      unsatisfactory outcome, despite appropriate management. Standards for the type
      and timing of treatment have not been established.

PMID- 16081017
TI  - Conditions of the calcaneus in skeletally immature patients.
AB  - Most conditions of the calcaneus in children, including calcaneal apophysitis,
      calcaneal fractures, and even intra-articular displaced fractures can be treated
      successfully with nonoperative methods. Calcaneal bone cysts require surgery only
      if symptomatic or at risk for pathologic fracture. Calcaneal osteomyelitis must
      be recognized and treated promptly to prevent severe complications.

PMID- 16081018
TI  - The medial approach to triple arthrodesis. Indications and technique for
      management of rigid valgus deformities in high-risk patients.
AB  - Between 1995 and 2002 the authors treated 17 patients who had a rigid hindfoot
      valgus deformity, and for whom a triple arthrodesis was planned, using a single
      medial incision. The indication for surgery was pain that was refractory to shoe
      wear, orthotic, and brace modifications. The severity of the hindfoot deformity
      itself was not a sufficient indication for this procedure. All 17 patients were
      examined a mean of 3.5 years following surgery (1-8 years). Subtalar and
      talonavicular arthrodesis was achieved in all patients and calcaneocuboid
      arthrodesis was achieved in 15 of 17 patients (2 asymptomatic pseudoarthrosis).
      The medial approach to triple arthrodesis is a reliable procedure, and can be
      used with a predictable outcome in patients who are at risk for wound healing
      complications for correction of hindfoot valgus deformity.

PMID- 16081019
TI  - Calcaneal osteotomies.
AB  - The current trend is to preserve the hindfoot joints to allow for more normal
      biomechanics and avoid arthritic changes in adjacent joints. Calcaneal
      osteotomies are effective in the treatment of hindfoot and foot malalignment with
      an acceptable rate of complications at medium-term follow-up. An important
      prerequisite should be flexibility and the absence of joint arthritis.

PMID- 16081020
TI  - Calcaneal tumors and tumor-like conditions.
AB  - Approximately 3% of osseous tumors occur in the foot and ankle. Solitary bone
      cysts, chondroblastoma, intraosseous lipoma, osteoid osteoma, chondrosarcoma, and
      Ewing's sarcoma seem to have a predilection for the calcaneus. Biopsy is often a
      crucial step in management. Tumor-like conditions, such as cysts, reactive
      lesions, and osteomyelitis, must be considered during evaluation. Treatment is
      often observation or curettage of benign lesions and resection or amputation for
      malignancies.

PMID- 16081021
TI  - [Contribution of registered and/or fused images to radiotherapy].
AB  - The quality of treatment that one can realize today in conformal radiotherapy,
      can be reached only if one has access to 3D imaging allowing a precise
      determination of the volume of the organs at risk and of the GTV. For this
      reason, one has access to anatomical imaging, CT or MRI, and functional and
      metabolic imaging, PET or SPECT imaging. CT gives the electronic density of the
      tissues, which is essential to ensure a very precise calculation of dose
      distribution. Its insufficiency in the visualization of the tumour and some
      anatomical structures makes necessary the registration of these images with MRI
      of which distortions are sufficiently weak to be usable in radiotherapy. The
      registration will be usable only if images of each modality are realised with the
      patient in treatment position, except for brain, where only CT, on which is based
      the registration, must be done in treatment position. The images registration is
      also called images fusion by some authors. Others consider fusion of images as a
      way to display registered images on a screen, specially for CT images and PET,
      and MRI and SPECT. Nevertheless, the fusion of images is a function offered by
      some softwares. It allows obtaining a single volume of voxels from those of the
      registered images (CT and MR images). This volume is not usable in radiotherapy
      because it keeps only partially the contributions of the CT scan images and the
      MRI. At least, if one wants to visualize the active parts of a tumour or to make
      the difference between fibrosis and tumour left or recurrence after radiotherapy
      or chemotherapy, it is necessary to use PET or SPECT. To define correctly the CTV
      using these images, one must realize the anatomical localization of the metabolic
      abnormalities, which they highlight with a registration based on CT or MRI. The
      difficulties to obtain the registration of these images led the manufacturer to
      propose mixed machines allowing realizing, at the same time, a CT imaging and a
      PET or a SPECT imaging with the patient in treatment position.

PMID- 16081022
TI  - [Target volumes in radiotherapy - head and neck tumors intensity - modulated
      radiation therapy (IMRT) of nasopharyngeal carcinoma: practical aspects in the
      delineation of target volumes and organs at risk].
AB  - The objective of this paper is to give some practical landmarks for the
      delineation of target volumes and organs at risk in Intensity Modulated Radiation
      Therapy for Nasopharyngeal Carcinoma. This delineation, drawn from anatomo
      clinical data, natural history of the disease and radiological pre-treatment
      evaluation, seems to be easier to define than the delineation of other head and
      neck cancer localisations (oropharynx and oral cavity for example). Experience
      inside national and international cooperative groups should tend to standardize
      this initial and fundamental step of Nasopharyngeal Conformal Radiotherapy.

PMID- 16081023
TI  - [Propositions for the selection and the delineation of peritumoral microscopic
      disease volumes in oral cavity and oropharyngeal cancers (lymph nodes excluded)].
AB  - This article reviews the concept of selectivity in peritumoral microscopic
      disease to be included in the Clinical Target Volume (CTV) for elective treatment
      for oral cavity and oropharyngeal squamous cell carcinoma, using the local
      tumoral spread. The objective of the present article is to present a procedure
      for the delineation of the target volumes, required for an appropriate
      application of 3-DCRT and IMRT for head and neck cancers. These propositions are
      for the delineation of microscopic peritumoral target volumes when external beam
      irradiation is required. CTVs are illustrated on CT sections.

PMID- 16081024
TI  - Neuropsychiatric features of systemic lupus erythematosus.
AB  - Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious and well known
      complication of systemic lupus erythematosus that remains a significant source of
      morbidity and mortality. Fortunately, advances in neuroimaging techniques and
      cognitive testing have improved the diagnosis of this disease and allowed earlier
      and more successful therapeutic intervention. Further, the association of NPSLE
      with the anti-phospholipid syndrome, other autoantibodies and inflammatory
      cytokines have also provided clues to the diagnosis and pathophysiology.
      Treatment of NPSLE is largely symptom based with outcome based on appropriate
      diagnosis.

PMID- 16081025
TI  - Animal models of spontaneous and drug-induced cutaneous lupus erythematosus.
AB  - Skin lesions are one of the most common manifestations of lupus erythematosus
      (LE) disorders such as systemic LE and discoid LE. The etiology of cutaneous LE
      is not fully understood. To address this issue, appropriate animal models
      frequently clarify the etiology and pathogenesis of autoimmune diseases, although
      no single animal model perfectly mimics a human disease. A common dermatological
      finding in many SLE-prone mouse strains is the deposition of immunoglobulins at
      the dermoepidermal junction. Over the past decade, the most exciting and
      important finding has been the discovery of the Fas-defect in the pathogenesis of
      the autoimmune MRL/lpr mouse, which is a good model for the spontaneous
      development of skin lesions similar to those seen in human LE. The analysis of
      MRL/lpr mice showed a close association between immunoglobulin deposits and the
      appearance of skin lesions. Transgenic and knock out mice have advanced the
      investigation of cutaneous LE. Furthermore, the model of drug-induced cutaneous
      LE can yield additional insight since the trigger is clear in drug-induced LE.
      Cutaneous LE lesions can also be induced in TCRalpha-/- mice treated with
      fluorouracil and ultraviolet B light irradiation. Studies on both spontaneous and
      experimental models will elucidate the pathogenesis of complicated and
      multifactorial cutaneous LE.

PMID- 16081026
TI  - Regulatory T cells: development, function and role in autoimmunity.
AB  - The crucial role of regulatory cells in self-tolerance and autoimmunity has been
      clearly established in numerous types of regulatory cells, the majority of which
      are CD4(+) T cells. Much focus has been placed on thymically derived
      CD4(+)CD25(+) regulatory T cells, given that the depletion of this subset in
      murine models results in the spontaneous development of autoimmune diseases.
      These naturally occurring regulatory T cells are found to be functionally mature
      in the thymus, and exert suppression in a contact-dependent manner. Another
      important category of immunosuppressive cells consists of conditionally induced
      regulatory T cells such as Tr1, Th3, and various other CD4(+) lymphocytes.
      Understanding the development and regulatory functions of immunoregulatory cells
      may elucidate the etiology for loss of self-tolerance. This review will summarize
      the characteristics, developmental pathways, and functions of regulatory T cells,
      as well as their role in human autoimmune diseases including multiple sclerosis,
      rheumatoid arthritis, Myasthenia Gravis, Kawasaki disease, autoimmune
      polyglandular syndrome type II, type 1 diabetes, autoimmune lymphoproliferative
      syndrome, and systemic lupus erythematosus.

PMID- 16081027
TI  - Mannose binding lectin: genetics and autoimmune disease.
AB  - Mannose binding lectin (MBL) is a serum protein with structure and functions
      similar to those of complement factor C1q, and is a key molecule in innate
      immunity. Interestingly, absence or extremely low concentration of serum MBL (MBL
      deficiency) seems to be a risk factor for occurrence of autoimmune diseases, in
      particular systemic lupus erythematosus. In addition, individuals with MBL
      deficiency are at risk of infection when in immunocompromised conditions. The
      concentration of serum MBL is greatly influenced by relatively common single
      nucleotide polymorphisms of the MBL gene. Therefore, typing of the MBL gene, or
      measurement of serum MBL may be valuable for determining the risk of infections
      in patients with systemic autoimmune diseases, who frequently undergo
      immunosuppressive therapies. MBL deficiency may also be a risk factor for
      atherosclerosis and arterial thrombosis, both being common complications of
      autoimmune diseases. On the other hand, MBL may be pathological in tissue
      injuries, and the precise roles of MBL in autoimmune diseases, and the value of
      MBL gene typing or serum MBL measurement in a clinical setting are yet to be
      clarified. Recently, presence of anti-MBL autoantibodies in sera of SLE patients
      has been reported. The significance of this autoantibody remains to be
      elucidated.

PMID- 16081028
TI  - NOD mice and autoimmunity.
AB  - The NOD mouse has been an important model of type 1 diabetes and autoimmune
      diseases for over 20 years. Experimental and genetic manipulations of the NOD
      mouse have demonstrated a broad susceptibility to multiple autoimmune syndromes.
      This predisposition to autoimmunity is due to defects in both central and
      peripheral tolerance. The defect of central tolerance is likely secondary to
      improper negative selection mediated by the unique MHC Class II molecule, I-A(g7)
      as well as intrinsic T cell signaling defects. The genetic basis for impaired
      peripheral tolerance is controlled by over 20 susceptibility loci termed insulin
      dependent diabetes (idd) loci. The maintenance of peripheral tolerance is
      impaired by alterations in T cell signaling and apoptosis. In addition,
      insufficient co-stimulation from accessory cells, and defective regulatory T
      cells, may promote the production of autoreactive T cells.

PMID- 16081029
TI  - Apoptotic modifications affect the autoreactivity of the U1 snRNP autoantigen.
AB  - A hallmark of systemic autoimmune diseases is the presence of high titers of
      serum autoantibodies targeting a diversity of autoantigens. Most components of
      the U1 snRNP complex are autoantigenic in systemic lupus erythematosus (SLE) and
      SLE overlap syndrome, which is also called mixed connective tissue disease
      (MCTD). It is hypothesized that posttranslational modifications, in particular
      cell death-associated modifications, play an important role in breaking tolerance
      to self-antigens. Recently, it became clear that the U1 snRNP particle, more
      specifically its U1-70K protein component, displays a new epitope during
      apoptosis. This review intends to give an overview of the modifications that
      occur on the U1 snRNP autoantigens, especially those arising during cell death,
      to summarize recent data describing autoantibody reactivities with apoptosis
      specific epitopes on the U1 snRNP complex, and to provide some insight into the
      mechanisms that might underlie the immune response to self-antigens.

PMID- 16081030
TI  - Additional diagnostic and clinical value of anti-cyclic citrullinated peptide
      antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis.
AB  - In the past decade significant advantages have been made in the treatment of
      rheumatoid arthritis (RA) and therapeutic strategies have changed a lot. These
      days, highly effective disease modifying anti-rheumatic drugs enable intervention
      early in the disease process, in order to prevent major joint damage. For years,
      serological support in the diagnosis of RA has been limited to the presence of
      rheumatoid factors, although not very specific for RA. During the last years a
      variety of circulating non-RF antibodies have been discovered and reported to be
      of potential diagnostic value. CCP2 proved to be a very disease-specific and even
      sensitive marker for RA. In addition to the diagnostic properties, CCP showed to
      be a good prognostic marker, CCP helps to predict the erosive or nonerosive
      progression of the disease, and CCP is already present early in the disease. This
      diagnostic tool enables the clinician to choose the optimal therapeutic
      management for each single RA patient.

PMID- 16081031
TI  - Immunotherapy of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a remarkably heterogeneous multisystem
      autoimmune disease. Improved understanding of the immunopathogenesis of this
      disorder over the past two decades is now being applied to therapy, with
      treatment being directed at specific immunological targets. This review will
      focus on both new uses for established therapies as well as on the introduction
      of novel agents. It is premature to claim that any one agent has superior
      efficacy to current therapies. However, the willingness of investigators
      supported by the pharmaceutical and biotechnology industries to evaluate the
      efficacy and safety of new products in controlled clinical trials may provide
      answers.

PMID- 16081032
TI  - Autoimmunity, alloimmunization and immunotherapy of AIDS.
AB  - The nature of clinical and physiological manifestations associated with HIV
      infection suggests that AIDS is an autoimmune disease. The conventional
      immunotherapeutic approaches aimed at enhancing the immune response against HIV
      have repeatedly failed when applied in the clinical practice. The results of
      several dozen therapeutic AIDS vaccine trials have consistently shown that while
      in vitro measured HIV-specific immune responses were evident as a result of
      vaccination the clinical improvement has been seldom observed. The clinical
      benefit, however, was invariably associated with the usage of vaccines that acted
      in accord with the principles of alloimmunization. The majority of these vaccines
      were derived from the blood of HIV carriers or a cell culture and thus they
      inherently contained alloantigens unrelated to HIV. The clinical experience with
      alloimmunization in a range of autoimmune diseases indicates that immune
      tolerization is an active immune process with benefits the vaccinees. The
      alloimmunization, which primarily induces tolerance rather than immune
      activation, might be a better strategy for the immunotherapy of AIDS.

PMID- 16081033
TI  - Kinetics of photochromic reactions in condensed phases.
AB  - A review of kinetic data reported for a few organic photochromic systems is
      given. The kinetics of processes taking place in solid matrices and in crystals
      was briefly discussed. The effect of solid matrices manifests itself in the
      kinetics being controlled by distributions rather than by discrete rate
      constants. The photochromic reactions often require a substantial free volume to
      occur, hence they seldom take place in crystals without a destruction of the
      crystal lattice. The activation energies of thermally driven reactions are in
      this case related rather to crystal parameters than to the reactions themselves.

PMID- 16081034
TI  - Analysis of hyaluronan content in chondroitin sulfate preparations by using
      selective enzymatic digestion and electrospray ionization mass spectrometry.
AB  - Two important glycosaminoglycans (GAGs) with structural roles in the body's
      cartilage are hyaluronan (HA) and chondroitin sulfate (CS). A simple mass
      spectrometric method for determining the amount of HA that may be present in
      isolated CS samples is presented in this article. Samples are subjected to
      selective enzymatic digestion using a bacterial hyaluronidase (HA lyase, EC
      4.2.2, from Streptococcus dysgalactiae) specific for HA. Undigested CS GAG is
      then removed by centrifugal filtration, and digested HA left in the filtrate is
      quantified by electrospray ionization mass spectrometry using an internal
      standard and selected ion monitoring. The described method was applied to the
      analysis of several CS samples prepared for use in nutritional supplements.

PMID- 16081035
TI  - Effect of gazing at the camera during a video link on recall.
AB  - The impact of looking into the camera during a presentation over a video link
      (resulting in the perception of mutual gaze) on information recall was
      investigated. In a face-to-face context mutual gaze has been shown to facilitate
      the encoding and subsequent recall of information [Fry, R., Smith, G.F., 1975.
      The effects of feedback and eye contact on performance of a digit-coding task. J.
      Soc. Psychol. 96, 145-146; Otteson, J.D., Otteson, C.R., 1980. Effect of
      teacher's gaze on children's story recall. Percept. Motor Skill. 50, 35-42;
      Sherwood, J.V., 1988. Facilitative effects of gaze upon learning. Percept. Motor
      Skill. 64 (3 Part 2), 1275-1278]. One explanation for these findings is that gaze
      acts as an arousal stimulus, which increases attentional focus and therefore
      enhances memory [Kelley, D.H., Gorham, J., 1988. Effects of immediacy on recall
      of information. Commun. Edu. 37(3), 198-207]. Two studies were conducted in order
      to test whether gazing at the camera during video-mediated presentations resulted
      in similar benefits as mutual gaze in a face-to-face context. In study 1 a
      confederate presented information about two fictitious soap products. In one
      condition, the confederate gazed at the camera for 30% of the presentation,
      therefore giving the participants the impression that he was gazing in their
      direction. In the other condition the confederate did not gaze at the camera.
      Participants viewed the sales presentations from both conditions. In the
      condition where gaze was directed at the camera, participants recalled
      significantly more information about the sales presentation. Study 2 employed the
      same pre-recorded sales presentations used in study 1, however they were
      delivered to the participants under audio-only conditions (therefore, the image
      was switched off). Results from study 2 indicated no recall differences between
      the two conditions. Findings from these studies would seem to indicate that the
      perception of gaze aversion over a video link (a consequence of the salesman not
      looking into the camera) has a negative impact on information recall. This has
      practical implications for video-mediated presentations. In a distance learning
      environment lecturers could be advised to look into the camera in order to
      promote more efficient learning in students.

PMID- 16081036
TI  - Rapid penetration of lucifer yellow into vital teeth and dye coupling between
      odontoblasts and neighbouring pulp cells in the cat.
AB  - The location and long process of odontoblasts appear well suited to detection of
      external stimuli. The odontoblasts may transmit the information not individually
      but as a syncytium via gap junction, which functions as a mechanism for
      intercellular linking cells and as the route for dye coupling. The aims of the
      present study were to examine dye penetration through enamel and dentin, and to
      confirm dye coupling between odontoblasts (OBs) or between odontoblasts and other
      pulpal cells beneath the odontoblastic layer (PCs). Either lucifer yellow (LY) or
      borate buffer (control) was applied to etched enamel surface of feline canines
      for 30 min at atmospheric pressure. In the decalcified sections, lucifer yellow
      positive cells were found not only in but also beneath the odontoblastic layer
      (experiment 1). In the isolated pulp cells, all OBs (27/27) and some PCs (6/9)
      that were immunocytochemically differentiated using two monoclonal antibodies
      were labelled with LY (experiment 2). These results indicate the remarkably quick
      movement of LYE through enamel and dentin into the superficial pulp. In
      experiment 3, fresh OBs and PCs were isolated from feline canines to which LY had
      not been applied. LY was iontophoretically injected into an OB-like cell that had
      an oval cell body and a long monopolar process. Some PCs and OBs identified
      immunocytochemically were labelled with LY, with the exception of a few LY
      negative cells. These findings indicate that dye coupling exists not only between
      OBs but also between OBs and PCs. Thus, the coupling provides evidence for a
      functional link via which information is transmitted between OBs and PCs.

PMID- 16081037
TI  - Role of GPR40 in fatty acid action on the beta cell line INS-1E.
AB  - GPR40 is a G protein-coupled receptor expressed preferentially in beta cells,
      that has been implicated in mediating free fatty acid-stimulated insulin release.
      GPR40 RNAi impaired the ability of palmitic acid (PA) to increase both insulin
      secretion and intracellular calcium ([Ca2+]i). The PA-dependent [Ca2+]i increase
      was attenuated by inhibitors of Galphaq, PLC, and SERCA. Thus GPR40 activates the
      Galphaq pathway, leading to release of Ca2+ from the ER. Yet the GPR40-dependent
      [Ca2+]i rise was dependent on extracellular Ca2+ and elevated glucose, and was
      blocked by inhibition of L-type calcium channels (LTCC) or opening of the K(ATP)
      channel; this suggests that GPR40 promotes Ca2+ influx through up-regulation of
      LTCC pre-activated by glucose and membrane depolarization. Taken together, the
      data indicate that GPR40 mediates the increase in [Ca2+]i and insulin secretion
      through the Galphaq-PLC pathway, resulting in release of Ca2+ from the ER and
      leading to up-regulation of Ca2+ influx via LTCC.

PMID- 16081038
TI  - Novel allele of the endothelial nitric oxide synthase gene polymorphism in
      Caucasian asthmatics.
AB  - The purpose of the present study was to investigate an association of the
      endothelial nitric oxide synthase (eNOS) gene polymorphism with asthma. eNOS
      intron4 variable number of tandem repeats (27 bp repeats) genotypes were
      determined in asthma patients and control subjects using microplate PCR. The
      Caucasian Asthma patients displayed three alleles while Caucasian controls
      displayed only two alleles. However, African Americans displayed all three
      alleles in both asthma patients and controls. African American controls displayed
      significantly higher a allele, significantly lower b allele, as well as c allele
      than those in Caucasians. This was the first report to show that there was a
      novel eNOS genotype present in asthmatic patients but not in control subjects in
      the Caucasian Community. The novel allele which we termed the c allele, could be
      a significant risk factor in the etiology of asthma in Caucasians. This novel
      allele could be involved in higher levels of NO in our Caucasian asthmatics.

PMID- 16081039
TI  - Abeta-polyacrolein aggregates: novel mechanism of plastic formation in senile
      plaques.
AB  - High levels of acrolein (H2C=HC-CH=O) occur in Alzheimer's brain. Amyloid-beta
      (Abeta) peptide co-localizes with acrolein presumably due to Abeta-induced lipid
      peroxidation. Focal production of acrolein may yield a transient elevation in the
      concentration of acrolein that may be susceptible to polymerization via basic
      latex polymer chemistry. Following incubation of Abeta with acrolein (16-750 mM),
      we observed the formation of thin plastic fragments that were extensively
      punctuated. Planar aggregates stained for protein and for cross-beta structures
      suggesting an Abeta-polyacrolein colloidal mixture. Depending on acrolein
      concentration and incubation time, we observed uniformly sized planar aggregates
      (approximately 10 microm2) or monolayers (>100 mm2) of thin polyacrolein films
      embedded with Abeta oligomers. The ability of Abeta to catalyze the
      polymerization of acrolein is likely due to Abeta's surfactant and redox
      properties. These observations suggest that plastic in the form of Abeta
      polyacrolein latexes may exist in neural tissue contributing to the pathogenesis
      of Alzheimer's disease.

PMID- 16081040
TI  - Engineered alpha-synuclein prevents wild type and familial Parkin variant fibril
      formation.
AB  - Alpha-synuclein is a major component of several pathological lesions diagnostic
      of specific neurodegenerative disease such as Parkinson's disease. This study
      focuses on the non-amyloid beta component of Alzheimer's disease amyloid, a key
      region for the aggregation and fibril formation of alpha-synuclein. Several
      mutations were introduced in an attempt to repress beta-strand formation and
      hydrophobic interaction-based aggregation. Although reducing the hydrophobicity
      drastically decreased fibril formation, the Val70Thr and Val70Pro mutations
      resulted in an unstable secondary structure thereby increasing non-structural
      aggregation, instead of fibril formation. Therefore, the stabilization of non
      structural natively unfolded status is important to prevent alpha-synuclein
      fibril formation. Mixing the Val70Thr/Val71Thr double mutant, which has
      inherently low potential, with the fibril forming alpha-synucleins, WT and
      Ala53Thr, greatly reduced their fibril formation and aggregation. This double
      mutant has great potential for further therapeutic approaches.

PMID- 16081041
TI  - Promoter analysis of Mucor rouxii delta9-desaturase: its implication for
      transcriptional regulation in Saccharomyces cerevisiae.
AB  - Promoter study was performed to understand the transcriptional control of delta9
      desaturase gene of Mucor rouxii. Several putative cis-elements involved in lipid
      metabolism were mapped by computational analysis. 5' deletion analysis shows the
      presence of elements with repressing activity, especially in 122 bp located
      upstream of the transcription start site. Truncation of these repressor domains
      showed that the promoter of M. rouxii is functional in Saccharomyces cerevisiae
      without additional components and is insensitive to nutritional depletion. The
      promoter also drove effectively the expression of a M. rouxii delta12-desaturase
      gene, and the linoleic acid content increased with the age of the yeast culture
      in parallel with the promoter activity. This approach provides a genetic tool for
      programming heterologous protein production in the yeast.

PMID- 16081042
TI  - A novel method for the intracellular delivery of siRNA using microbubble-enhanced
      focused ultrasound.
AB  - Short interfering RNA (siRNA) has attracted much attention for clinical use in
      various diseases. However, its delivery, especially through the cell membrane,
      continues to present a challenge. Advances in ultrasound- and ultrasound contrast
      agent technologies have made it possible to change transiently the permeability
      of the cell membrane and, using a focused ultrasound transducer, to narrow and
      focus the ultrasound energy on a small target, thereby avoiding damage to
      surrounding tissue. In this in vitro study, we demonstrate that it is possible to
      deliver siRNA intracellularly via microbubble-enhanced focused ultrasound.
      Although further optimization is necessary, our novel method for siRNA
      transduction represents a powerful tool for using siRNA in vivo and possibly in
      the clinical setting.

PMID- 16081043
TI  - The D-domain of Sp3 modulates its protein levels and activation of the
      p21(CIP1/WAF1) promoter.
AB  - A variety of signals result in the transcriptional induction of the
      p21(CIP1/WAF1) promoter and both Sp1 and the related Sp3 proteins have been
      implicated in this induction. We have characterized the role of the C-terminal D
      domains of both Sp1 and Sp3 proteins in the activation of this promoter in
      response to butyrate treatment of Hep G2 cells. We have defined a negative
      regulatory domain present in the C-terminus of Sp3. This domain decreases Sp3
      protein levels, and this property can be transferred to Sp1. Changes in Sp3
      protein levels may bring about growth arrest through the induction of inhibitors
      of the cell cycle such as p21(CIP1/WAF1).

PMID- 16081044
TI  - Divergent effects of zinc depletion in brain vs non-brain endothelial cells.
AB  - Dietary zinc deficiency is common in developing as well as developed countries.
      Endothelial cells (EC) lining the inner surface of peripheral blood vessels are
      sensitive to zinc deficiency and lose structural integrity when exposed to
      culture media low in zinc or to zinc chelators. In contrast, we demonstrate here
      that human brain microvascular EC (HBMEC), which constitute the blood-brain
      barrier (BBB), resist zinc depletion and respond by enhancing their barrier
      function. This response was specific for HBMEC and did not occur in non-brain EC,
      such as human umbilical vein endothelial cells, human aortic endothelial cells,
      and human iliac vein endothelial cells. Our results suggest the presence of
      specific mechanisms to counteract zinc deficiency at the BBB, likely involving
      HBMEC junctional complexes. Understanding the mechanisms involved in this unique
      response might provide means to modulate the BBB dysfunction associated with
      neurological disorders such as stroke, multiple sclerosis, and Alzheimer's
      disease.

PMID- 16081045
TI  - Tandem screening of toxic compounds on GFP-labeled bacteria and cancer cells in
      microtiter plates.
AB  - A 96-well fluorescence-based assay has been developed for the rapid screening of
      potential cytotoxic and bacteriocidal compounds. The assay is based on detection
      of green fluorescent protein (GFP) in HeLa human carcinoma cells as well as gram
      negative (Escherichia coli) and gram positive bacteria (Mycobacterium avium).
      Addition of a toxic compound to the GFP marked cells resulted in the loss of the
      GFP fluorescence which was readily detected by fluorometry. Thirty-nine distinct
      naphthoquinone derivatives were screened and several of these compounds were
      found to be toxic to all cell types. Apart from differences in overall toxicity,
      two general types of toxic compounds were detected, those that exhibited toxicity
      to two or all three of the cell types and those that were primarily toxic to the
      HeLa cells. Our results demonstrate that the parallel screening of both
      eukaryotic and prokaryotic cells is not only feasible and reproducible but also
      cost effective.

PMID- 16081046
TI  - The ultimate tryptophan residue of neprilysin 2 is not involved in protein
      maturation and enzymatic activity.
AB  - Modeling the three-dimensional structure of neprilysin 2 (NEP2) using the crystal
      structure of neprilysin as template revealed that their active sites share many
      common features, though slight differences therein cannot completely account for
      their specific pharmacological profiles. Recent evidence also suggest that
      residues outside the active site can play crucial functions in the maturation and
      enzymatic activity of these metalloproteases. To further explore the functions of
      amino acids in the acquisition and maintenance of the NEP2 structure, site
      directed mutagenesis of conserved residues involved in the enzymatic activity of
      ECE-1 was performed. In particular, the ultimate tryptophan residue of ECE-1 was
      recently shown to be important in its activation. This residue was thus mutated
      in the secreted isoform of NEP2, as were proline residues located in its
      vicinity. Expression of these mutants in AtT20 cells and study of their secretion
      and catalytic activities shows that while the ultimate tryptophan residue of the
      NEP2 sequence is not essential to its proper and activity, structural changes in
      its vicinity can have a severe impact on the maturation processes involved in the
      activation of NEP2.

PMID- 16081047
TI  - [6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and
      in vivo.
AB  - [6]-Gingerol, a pungent ingredient of ginger (Zingiber officinale Roscoe,
      Zingiberaceae), has anti-bacterial, anti-inflammatory, and anti-tumor-promoting
      activities. Here, we describe its novel anti-angiogenic activity in vitro and in
      vivo. In vitro, [6]-gingerol inhibited both the VEGF- and bFGF-induced
      proliferation of human endothelial cells and caused cell cycle arrest in the G1
      phase. It also blocked capillary-like tube formation by endothelial cells in
      response to VEGF, and strongly inhibited sprouting of endothelial cells in the
      rat aorta and formation of new blood vessel in the mouse cornea in response to
      VEGF. Moreover, i.p. administration, without reaching tumor cytotoxic blood
      levels, to mice receiving i.v. injection of B16F10 melanoma cells, reduced the
      number of lung metastasis, with preservation of apparently healthy behavior.
      Taken together, these results demonstrate that [6]-gingerol inhibits angiogenesis
      and may be useful in the treatment of tumors and other angiogenesis-dependent
      diseases.

PMID- 16081048
TI  - Evaluation of potential Stat3-regulated genes in human breast cancer.
AB  - The constitutive activation of signal transducer and activator of transcription 3
      (Stat3) is frequently detected in breast cancer tissues and cell lines. Stat3 has
      been classified as a proto-oncogene, because an activated form of Stat3 can
      mediate oncogenic transformation in cultured cells and tumor formation in nude
      mice. Since Stat3 may play an important role in breast cancer, it is of interest
      to investigate the expression of phosphorylated Stat3, an activated form of
      Stat3, and its downstream mediators specifically in breast cancer, and to explore
      the possible mechanisms of Stat3 signaling pathway in oncogenesis of breast
      cancer. We analyzed Stat3 phosphorylation and expression of Stat3-regulated genes
      in breast cancer cell lines as well as invasive breast cancer tissues using
      tissue microarray slides. Our results showed that elevated levels of
      phosphorylation of Stat3 protein (Tyr705) were detected in 48 out of total 136
      invasive breast tumors (35%) whereas normal breast tissues express much lower
      levels of Stat3 phosphorylation. The increased levels of Stat3 phosphorylation
      were associated with the metastasis in regional lymph nodes (P=0.042) and the
      expression of progesterone receptor (P=0.028) but not with distant metastasis,
      nor the expression of estrogen receptor. Our results also indicate that elevated
      levels of Stat3 phosphorylation were significantly associated with increased
      expression of potential downstream targets of Stat3 which include apoptosis
      inhibitors (Survivin, Mcl-1, HSP27, Adrenomedullin, and Bcl-xL), cell-cycle
      regulators (c-Fos, MEK5, and c-Myc), and inducer of tumor angiogenesis (VEGF, COX
      2, MMP-2, MMP-10, and MMP-1) in invasive breast cancer tissues. Therefore, our
      findings suggest that constitutive Stat3 signaling may be one of the key upstream
      regulators to induce these downstream proteins, which may play important roles in
      Stat3-mediated oncogenesis in breast cancer.

PMID- 16081049
TI  - Protein kinase D3 activation and phosphorylation by signaling through G alpha q.
AB  - PKD is the founding member of a novel protein kinase family that also includes
      PKD2 and PKD3. PKD has been the focus of most studies up to date, but little is
      known about the mechanisms that mediate PKD3 activation. Here, we demonstrate
      that PKD3 immunoprecipitated from COS-7 cells transfected with a constitutively
      active G alpha q subunit (alpha(q)Q209L) exhibited a marked increase in basal
      activity. Addition of aluminum fluoride to cells co-transfected with PKD3 and
      wild type G alpha(q) also induced PKD3 activation. G alpha(q)-mediated PKD3
      activation is associated with persistent translocation of PKD3 from both cytosol
      and nucleus to plasma membrane. Expression of a COOH-terminal fragment of G alpha
      q that acts in a dominant-negative fashion attenuated PKD3 activation in response
      to bombesin receptor stimulation. Our results indicate that G alpha q activation
      is sufficient to stimulate sustained PKD3 activation and show that the endogenous
      G alpha q is a major component in the signaling pathway that mediates bombesin
      induced PKD3 activation.

PMID- 16081050
TI  - Effect of the digitoxigenin derivative, INCICH-D7, on Na+, K+-ATPase.
AB  - Compound 14beta,17beta-cycloketoester-3beta-OH androstane (INCICH-D7) is a
      semisynthetic product of a structural modification of the digitoxigenin molecule.
      INCICH-D7 has a heterocyclic ketoester type fusion between positions C14 and C17
      of the steroid nucleus, which confers this molecule stronger electronegativity
      than that of digitoxigenin. INCICH-D7 retained positive inotropic effect, with a
      greater safety margin, when compared to digitoxigenin and ouabain. In this study
      we have examinated the INCICH-D7 effect on Na+, K+-dependent
      adenosinetriphosphatase (Na+, K+-ATPase) and compared these results with the ones
      observed with digitoxigenin and ouabain. The inhibitory effect of INCICH-D7 on
      Na+, K+-ATPase was five times lower (IC50=4 microM) than that of ouabain
      (IC50=0.8 microM) and 70 times lower than that of digitoxigenin (IC50=0.06
      microM). The inhibitory effect of INCICH-D7 and ouabain on the enzyme was
      irreversible while digitoxigenin's one was reversible in up to an 80%. Our
      results indicate that inclusion of the heterocycle between positions C14 and C17
      in the digitoxigenin molecule lowers significantly the inhibitory effect on Na+,
      K+-ATPase and renders the interaction between INCICH-D7 and enzyme irreversible
      under the studied reaction conditions.

PMID- 16081051
TI  - Isoflurane preconditioning decreases glutamate receptor overactivation-induced
      Purkinje neuronal injury in rat cerebellar slices.
AB  - A brain slice model was used to test the hypothesis that preconditioning with
      isoflurane, a commonly used volatile anesthetic in clinical practice, reduces
      neuronal injury caused by overstimulation of glutamate receptors. Glutamate
      receptors were stimulated by various concentrations of glutamate for 20 min, N
      methyl-d-aspartate (NMDA) for 15 min or alpha-amino-3-hydroxy-5-methyl-4-isoxazol
      propionic acid (AMPA) for 15 min. Morphology of Purkinje neurons in the
      cerebellar slices of adult male Sprague-Dawley rats was evaluated 5 h after the
      agonist stimulation. Glutamate, NMDA and AMPA induced a dose-dependent decrease
      in the percentage of morphologically normal Purkinje neurons. The concentration
      to induce the maximal neurotoxic effect was 300 microM for glutamate, 300 microM
      for NMDA and 30 microM for AMPA. Isoflurane preconditioning (2% isoflurane for 30
      min and then a 15-min rest period before the agonist stimulation) significantly
      reduced the neurotoxicity induced by 300 microM glutamate, 300 microM NMDA or 30
      microM AMPA. Isoflurane preconditioning-induced protection against glutamate
      neurotoxicity was abolished by two protein kinase C (PKC) inhibitors, calphostin
      C (0.5 microM) and chelerythrine (5 microM), or a nitric oxide synthase (NOS)
      inhibitor, l-nitro(G)-arginine methyl ester (l-NAME, 1.5 mM), but was not
      affected by an adenosine A1 receptor inhibitor, 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX, 300 nM), or a Gi protein inhibitor, pertussis toxin
      (PTX, 200 ng/ml). Isoflurane preconditioning-induced protection against NMDA
      neurotoxicity was also abolished by calphostin C, chelerythrine or l-NAME. Thus,
      isoflurane preconditioning reduced glutamate receptor overstimulation-induced
      neuronal injury/death. This neuroprotection may be PKC- and NOS-dependent.

PMID- 16081052
TI  - Distribution of galanin receptor 1-immunoreactive neurons in the ovine
      hypothalamus: colocalization with GnRH.
AB  - Galanin is implicated in numerous physiological functions, including
      reproduction. Where and how galanin acts in the brain is poorly understood, but
      recent evidence suggests that it is predominantly through the GAL-R1 receptor.
      Using an antibody raised against the third intracellular loop of rat GAL-R1, a
      region that is highly conserved among species, our first objective was to
      determine the distribution of cells expressing immunoreactive GAL-R1 in the
      hypothalamus of the sheep. GAL-R1-immunoreactive cells were spread widely in the
      ovine diencephalon and overlapped with the known distribution of GnRH neurons.
      Galanin has been shown to enhance GnRH secretion, but it is not known whether
      this effect is transduced at the level of the GnRH neuron or is indirect. Thus,
      our second objective was to establish if GnRH neurons throughout the hypothalamus
      expressed GAL-R1 receptors and, if so, whether GAL-R1 expression in GnRH neurons
      was influenced by season, gender and/or stage of the estrous cycle. In rams and
      ewes during the non-breeding season, only a tenth of the GnRH neurons expressed
      immunocytochemically detectable GAL-R1 receptors. In contrast, a fifth of the
      GnRH neurons expressed immunocytochemically detectable GAL-R1 in the luteal
      phase, whereas only a twentieth expressed GAL-R1 in the follicular phase. These
      data suggest that galanin may affect a subpopulation of GnRH neurons through the
      GAL-R1 receptor and that this affect may be modulated by steroids.

PMID- 16081053
TI  - Effects of neonatal C-fiber depletion on neocortical long-term potentiation and
      depression.
AB  - Capsaicin (Cap)-induced depletion of C-fiber afferents results in plasticity of
      somatosensory system which is manifested as a functional alteration at different
      levels of the somatosensory pathway. In the present study we examined the effect
      of Cap-induced neonatal depletion of C-fibers on the induction of long-term
      potentiation (LTP) and long-term depression (LTD) in the neocortex of freely
      moving rats. A stimulating electrode was implanted into corpus callosum and a
      recording electrode was implanted in the somatosensory cortex of control (Con:
      normal, without electrical stimulation), trained (normal, with electrical
      stimulation) and Cap-treated (C-fiber depleted, with electrical stimulation)
      adult rats. Two weeks after the surgery, evoked field potential responses were
      recorded before, during (12 days) and after (1 month) the induction period of LTP
      and LTD. The LTP and LTD response characteristics during the time course of
      recording were compared between different groups. In the train group, LTP and LTD
      appeared after 3 days of stimulation. LTP magnitude peaked after about 6 days
      while LTD magnitude peaked in about 12 days. C-fiber depletion postponed the
      development of LTP and LTD making the highest differential levels of LTP about 6
      days after the initiation of LTP induction. The impact of C-fiber depletion on
      slowing the time course of LTD induction was more prolonged and lasted until day
      12 of the initiation of LTD induction. These results suggest that intact C-fibers
      are necessary for normal plasticity and long-term synaptic modification of the
      somatosensory system.

PMID- 16081054
TI  - Acute and repeated administration of cocaine differentially regulates expression
      of PSA-NCAM-positive neurons in the rat hippocampus.
AB  - Recent data indicating that addictive substances are able to alter brain
      plasticity and its morphology inclined us to determine whether acute and chronic
      cocaine administration could modify the expression of a polysialylated form of
      the neuronal cell adhesion molecule (PSA-NCAM) in the dentate gyrus of the rat
      hippocampus. Alterations in the PSA-NCAM expression are known to effect a variety
      of neuroanatomical rearrangements in the brain structure. Cocaine was
      administered acutely (15 mg/kg, i.p.) or repeatedly (15 mg/kg, i.p. once a day
      for five consecutive days). The number of PSA-NCAM immunopositive cells was
      determined at six time points after cocaine treatment: 6 h and 1, 2, 4, 6, and 10
      days (both in acute and repeated treatment). It was found that a single injection
      of cocaine induced a time-dependent decrease in the number of PSA-NCAM cells in
      the dentate gyrus. The decrease was observed on day 1 after cocaine treatment and
      lasted for at least 6 days. In contrast, an increase in the number of PSA-NCAM
      positive cells in the dentate gyrus was observed 2 and 4 days after the last dose
      of repeated cocaine. It is concluded that cocaine can evoke long-lasting changes
      in the PSA-NCAM protein expression in the dentate gyrus and that the direction of
      cocaine-induced PSA-NCAM changes depends on the regimen of cocaine
      administration. It is postulated that cocaine may have impact on hippocampal
      plasticity and subsequent processes that are controlled by plastic changes in the
      hippocampal structure.

PMID- 16081055
TI  - Long-term activation of c-Fos and c-Jun in optic nerve head astrocytes in
      experimental ocular hypertension in monkeys and after exposure to elevated
      pressure in vitro.
AB  - This study investigates whether the immediate early gene (IEG) products c-Fos and
      c-Jun are activated in vivo in monkeys with experimental glaucoma, and in vitro
      in cultured human ONH astrocytes exposed to hydrostatic pressure (HP). Three
      Rhesus monkeys with mild glaucomatous damage (mean intraocular pressure (IOP) 27
      +/- 1.3 mm Hg approximately 42 weeks) and three with moderate glaucomatous damage
      (mean IOP 44 +/- 6.7% mm Hg approximately 11 weeks) were used for this study; the
      contralateral eye served as normal control (mean IOP 18.6 +/- 1.7 mm Hg). ONH
      tissues were stained with GFAP, DAPI, and c-Jun or c-Fos, and transcription
      factor positive and negative nuclei were counted to determine nuclear
      localization. Cultured human normal and glaucomatous ONH astrocytes exposed to
      elevated HP served as the in vitro model of elevated pressure. Activation and
      nuclear localization of c-Fos and c-Jun increased significantly in the monkeys
      with elevated IOP. These data correlated with axonal loss, reactive astrocytes,
      and remodeling of the optic disc. Cultured human ONH astrocytes showed increased
      nuclear localization of c-Fos and c-Jun under exposure to HP.
      Immunohistochemistry demonstrated that the upstream regulators of c-Fos and c
      Jun, ERK-MAPK and MAPKp38 localized to the nuclei of ONH astrocytes in monkeys
      with experimental glaucoma. Taken together, these results demonstrate c-Fos and c
      Jun activation in ONH astrocytes in vivo and in vitro, and that activation of
      both transcription factors is associated with ERK and MAPKp38 activation in
      experimental glaucoma, suggesting that activation of transcription factors may
      participate in the induction and maintenance of the reactive astrocyte phenotype
      in glaucomatous optic neuropathy.

PMID- 16081056
TI  - Elevated TFPI levels in female hyperhomocysteinemic patients.
AB  - OBJECTIVES: Hyperhomocysteinemia is a risk factor for cardiovascular diseases,
      while tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of
      blood coagulation. We investigated the in vivo influence of elevated homocysteine
      concentrations on TFPI levels. METHODS: Total TFPI levels of 82
      hyperhomocysteinemic patients were determined. RESULTS: The patients' TFPI levels
      were significantly elevated compared to blood donors, with a more pronounced
      effect in females than in males. CONCLUSIONS: We have shown a gender-dependent
      TFPI elevation in hyperhomocysteinemic patients.

PMID- 16081057
TI  - Insulin and HOMA in Spanish prepubertal children: relationship with lipid
      profile.
AB  - OBJECTIVE: The effects of insulin or insulin resistance on the lipid profile seem
      to change with age. The aim of this study was to analyze insulin levels and an
      insulin resistance index and to investigate the relationship between these and
      the lipid profile in a population-based sample of Spanish prepubertal children.
      METHODS: 1048 (524 boys and 524 girls) randomly selected prepubertal children
      were studied. Children were 6 to 8 years old with a mean age of 6.7. Plasma
      lipid, FFA and insulin levels were measured. The homeostatic model assessment
      (HOMA) was calculated as an indicator of insulin resistance. RESULTS: When
      analyzing percentile values of insulin, HOMA and FFA by sex, we observed that
      girls had significantly higher insulin concentrations than boys (except at the
      10th percentile) and significantly higher FFA (except at the 90th percentile)
      with no significant differences between sexes for HOMA. Multivariate regression
      analyses showed that insulin was positively associated with glucose,
      triglycerides and apoB in boys but not in girls, and negatively associated with
      FFA in both genders. CONCLUSIONS: We report here data about the distribution of
      insulin in the Spanish prepubertal population. The higher levels of insulin in
      prepubertal girls could indicate that girls start to be more insulin resistant
      than boys at this age, although other manifestations of insulin resistance are
      not yet detectable.

PMID- 16081058
TI  - Never getting to zero: Elementary school students' understanding of the infinite
      divisibility of number and matter.
AB  - Clinical interviews administered to third- to sixth-graders explored children's
      conceptualizations of rational number and of certain extensive physical
      quantities. We found within child consistency in reasoning about diverse aspects
      of rational number. Children's spontaneous acknowledgement of the existence of
      numbers between 0 and 1 was strongly related to their induction that numbers are
      infinitely divisible in the sense that they can be repeatedly divided without
      ever getting to zero. Their conceptualizing number as infinitely divisible was
      strongly related to their having a model of fraction notation based on division
      and to their successful judgment of the relative magnitudes of fractions and
      decimals. In addition, their understanding number as infinitely divisible was
      strongly related to their understanding physical quantities as infinitely
      divisible. These results support a conceptual change account of knowledge
      acquisition, involving two-way mappings between the domains of number and
      physical quantity.

PMID- 16081059
TI  - Protein sequence-based risk classification for human papillomaviruses.
AB  - Human papillomaviruses (HPVs) are small DNA tumor viruses which infect epithelial
      tissues and induce hyperproliferative lesions. Infection by high-risk genital
      HPVs is associated with the development of anogenital cancers. Classification of
      risk types is important in understanding the mechanisms in infection and in
      developing novel instruments for medical examination such as DNA microarrays. The
      sequence-based classification methods are useful in classifying risk types by
      considering residues in conserved positions. In this paper, we present a machine
      learning approach to the classification of HPV risk types by using the protein
      sequences. Our approach is based on the hidden Markov model and the kernel
      method. The former searches informative subsequence positions and the latter
      computes efficiently to classify protein sequences. In the experiments, the
      classifier predicted four unknown HPV types exactly. An additional result shows
      that the kernel-based classifiers learned with more informative subsequences
      outperform the classifiers learned with the whole sequence or random
      subsequences.

PMID- 16081060
TI  - Modified scaled Fourier linear combiner in thoracic impedance cardiography.
AB  - New filtering algorithms; a modified scaled Fourier linear combiner (mSFLC) and a
      modified ensemble averaging (mEA) are proposed to remove the phase distortion of
      the impedance waveform caused by SFLC. Performance of the filters is assessed
      from the shape of the filtered waveform and the estimation of systolic time
      intervals. It was found that the mSFLC and mEA could compensate for drawbacks of
      the SFLC and precisely reproduce the impedance waveforms; however,
      misinterpretation and attenuation in the cardiac variables may be caused when
      abrupt changes or irregularities occur in the source waveform.

PMID- 16081061
TI  - Nuclear envelope breakdown may deliver an inhibitor of protein phosphatase 1
      which triggers cyclin B translation in starfish oocytes.
AB  - In vertebrates, enhanced translation of mRNAs in oocytes and early embryos
      entering M-phase is thought to occur through polyadenylation, involving binding,
      hyperphosphorylation and proteolytic degradation of Aurora-activated CPEB. In
      starfish, an unknown component of the oocyte nucleus is required for cyclin B
      synthesis following the release of G2/prophase block by hormonal stimulation. We
      have found that CPEB cannot be hyperphosphorylated following hormonal stimulation
      in starfish oocytes from which the nucleus has been removed. Activation of Aurora
      kinase, known to interact with protein phosphatase 1 and its specific inhibitor
      Inh-2, is also prevented. The microinjection of Inh-2 restores Aurora activation,
      CPEB hyperphosphorylation and cyclin B translation in enucleated oocytes.
      Nevertheless, we provide evidence that CPEB is in fact hyperphosphorylated by
      cdc2, without apparent involvement of Aurora or MAP kinase, and that cyclin B
      synthesis can be stimulated without previous degradation of phosphorylated CPEB.
      Thus, the regulation of cyclin B synthesis necessary for progression through
      meiosis can be explained by an equilibrium between CPEB phosphorylation and
      dephosphorylation, and both aspects of this control may rely on the sole
      activation of Cdc2 and subsequent nuclear breakdown.

PMID- 16081062
TI  - Maternal and umbilical cord blood levels of mercury, lead, cadmium, and essential
      trace elements in Arctic Canada.
AB  - Maternal and umbilical cord blood levels of mercury (Hg), lead (Pb), cadmium
      (Cd), and the trace elements copper (Cu), zinc (Zn), and selenium (Se) are
      reported for Inuit, Dene/Metis, Caucasian, and Other nonaboriginal participants
      from Arctic Canada. This is the first human tissue monitoring program covering
      the entire Northwest Territories and Nunavut for multiple contaminants and
      establishes a baseline upon which future comparisons can be made. Results for
      chlorinated organic pesticides and PCBs for these participants have been reported
      elsewhere. Between May 1994 and June 1999, 523 women volunteered to participate
      by giving their written informed consent, resulting in the collection of 386
      maternal blood samples, 407 cord samples, and 351 cord:maternal paired samples.
      Geometric mean (GM) maternal total mercury (THg) concentrations ranged from 0.87
      microg/L (SD = 1.95) in the Caucasian group of participants (n = 134) to 3.51
      microg/L (SD = 8.30) in the Inuit group (n = 146). The GM of the Inuit group was
      2.6-fold higher than that of the Dene/Metis group (1.35 microg/L, SD = 1.60, n =
      92) and significantly higher than those of all other groups (P<0.0001). Of Inuit
      women participants, 3% (n = 4) were within Health Canada's level of concern range
      (20-99 microg/L) for methylmercury (MeHg) exposure. Of Inuit and Dene/Metis cord
      samples, 56% (n = 95) and 5% (n = 4), respectively, exceeded 5.8 microg/L MeHg,
      the revised US Environmental Protection Agency lower benchmark dose. GM maternal
      Pb was significantly higher in Dene/Metis (30.9 microg/L or 3.1 microg/dL; SD =
      29.1 microg/L) and Inuit (31.6 microg/L, SD = 38.3) participants compared with
      the Caucasian group (20.6 microg/L, SD = 17.9) (P < 0.0001). Half of all
      participants were smokers. GM blood Cd in moderate smokers (1-8 cigarettes/day)
      and in heavy smokers (> 8 cigarettes/day) was 7.4-fold higher and 12.5-fold
      higher, respectively, than in nonsmokers. The high percentage of smokers among
      Inuit (77%) and Dene/Metis (48%) participants highlights the need for ongoing
      public health action directed at tobacco prevention, reduction, and cessation for
      women of reproductive age. Pb and THg were detected in more than 95% of all cord
      blood samples, with GMs of 21 microg/L and 2.7 microg/L, respectively, and Cd was
      detected in 26% of all cord samples, with a GM of 0.08 microg/L. Cord:maternal
      ratios from paired samples ranged from 0.44 to 4.5 for THg, from 0.5 to 10.3 for
      MeHg, and 0.1 to 9.0 for Pb. On average, levels of THg, MeHg, and Zn were
      significantly higher in cord blood than in maternal blood (P < 0.0001), whereas
      maternal Cd, Pb, Se, and Cu levels were significantly higher than those in cord
      blood (P < 0.0001). There was no significant relationship between methylmercury
      and selenium for the range of MeHg exposures in this study. Ongoing monitoring of
      populations at risk and traditional food species, as well as continued
      international efforts to reduce anthropogenic sources of mercury, are
      recommended.

PMID- 16081063
TI  - Adrenomedullin modulates COX-2 and HGF expression in reserpine-injuried gastric
      mucosa in the rat.
AB  - Here we show the increased hepatocyte growth factor (HGF) and cyclooxygenase-2
      (COX-2) expression in gastric mucosa of rats which have developed a reserpine
      induced ulcer. Such an increase of HGF and COX-2 expression was blunted in rats
      pretreated with adrenomedullin. Pretreatment with adrenomedullin and the
      adrenomedullin22-52 fragment did not result in changes of HGF and COX-2
      expression, compared to the reserpine and adrenomedullin treated group.
      Pretreatment with adrenomedullin and the calcitonin gene-related peptide8-37
      fragment (CGRP8-37) increased HGF and COX-2 expression, compared to the reserpine
      and adrenomedullin treated group. Our results suggest that the inhibitory effect
      of adrenomedullin on the expression of HGF and COX-2 is mediated by CGRP
      receptors.

PMID- 16081064
TI  - A study of cutaneous lesions caused by Leishmania mexicana in plasminogen
      deficient mice.
AB  - The role of plasminogen, the zymogenic form of the serine protease plasmin, was
      investigated in the infection of Leishmania mexicana in plasminogen-deficient
      (plg(-/-)) and Plg wild-type (plg(+/+)) mice. Differences in the lesion size were
      observed between male plg(+/+) and plg(-/-) mice. However, these differences were
      not observed in female mice. In both genders, examination of the lesion tissues
      at 8 weeks post-infection showed differences in the immunoreactivity pattern with
      anti-Leishmania antibodies. The parasites were limited to isolated foci in the
      plg(-/-) mice lesion, in contrast to the scattered pattern observed in plg(+/+)
      mice. These results support the hypothesis that the interaction of the parasite
      with the host plasminogen-plasmin system might contribute to the virulence of L.
      mexicana.

PMID- 16081065
TI  - Dual-specificity phosphatase DUSP1 protects overactivation of hypoxia-inducible
      factor 1 through inactivating ERK MAPK.
AB  - Hypoxia-inducible factor 1 (HIF-1) plays a critical role in controlling oxygen
      delivery and metabolic adaptation to hypoxic conditions in hypoxic tumor cells.
      HIF-1 activation is initiated by several factors including mitogen-activated
      protein kinase (MAPK) superfamily. We have previously reported that mitogen
      activated protein kinase phosphatase DUSP1 (MKP-1) was implicated in the negative
      regulation of HIF-1alpha subunit phosphorylation and HIF-1 activity. However, the
      molecular basis by which MKP-1 influences HIF-1 activity is not clarified. In
      this paper, we show that hypoxia transcriptionally induces MKP-1 expression in a
      time-dependent manner. Meanwhile, hypoxia also activates extracellular signal
      regulated kinase (ERK) whose activity is enhanced or reduced by MKP-1 suppression
      or MKP-1 overexpression, respectively. We also show that suppression of MKP-1
      expression facilitates the interaction between HIF-1alpha subunit and p300, a co
      activator of HIF-1. Moreover, MKP-1 suppression leads to enhanced HIF-1 activity,
      which can be counteracted by PD98059, an ERK kinase inhibitor. Taken together,
      the results presented here suggest that hypoxia-induced MKP-1 protects
      overactivation of HIF-1 activation through inhibiting ERK kinase activity.

PMID- 16081066
TI  - Remodeling of hippocampal GABAergic system in adult offspring after maternal
      hypoxia and magnesium sulfate load: immunohistochemical study.
AB  - A strong relationship between hypoxia and fetal brain damage has been described.
      Specific susceptibility of the GABAergic neurons to these conditions may be
      crucial to the damage induced. We have previously shown, in a mouse model, that
      maternal pretreatment with magnesium sulfate (Mg) partially prevented the
      behavioral consequences of maternal hypoxia in the adult offspring. Here, we
      tested the effect of maternal hypoxia and maternal Mg load on the GABAergic
      system of 8-month-old offspring. The immunoreactivity (IR) of several proteins
      expressed in GABAergic neurons and inhibitory synapses was analyzed in the
      following regions of the adult offspring brain: hippocampus, cortical M1, caudate
      putamen, and lateral globus pallidus. Maternal hypoxia reduced the density of
      parvalbumin (PV)-IR neurons in the hippocampus. The density of PV-IR and
      calbindin (CB)-IR neurons was also reduced in the deep and superficial layers of
      the M1. Maternal pretreatment with Mg had a prophylactic action in the
      superficial, but not the deep, layers of M1. Also, in offspring from the maternal
      hypoxia group, the vesicular GABA transporter (VGAT)-IR was enhanced in the
      hippocampal CA1 and hilus regions. No effect of maternal hypoxia on VGAT-IR was
      observed in the M1. However, maternal pretreatment with Mg enhanced VGAT-IR and
      glutamate decarboxylase-IR in the deep layers of the M1. In the globus pallidus,
      maternal hypoxia enhanced CB-IR, which was prevented by maternal pretreatment
      with Mg. In conclusion, maternal hypoxia induced a loss of PV-IR and CB-IR
      neurons; maternal pretreatment with Mg partially protected these neuron
      populations. An increase in proteins of inhibitory synapses, observed under
      hypoxic conditions in several brain regions, may be a result of some compensatory
      mechanism.

PMID- 16081067
TI  - Expression of neuritin during liver maturation and regeneration.
AB  - Cell surface molecules are not only important for cell-cell interactions but also
      useful for a marker to define cell types and differentiation stages. Unlike
      hematopoietic system in which numerous such antigens have been identified, only a
      few cell surface molecules have been used to define differentiation stage of
      hepatocytes. In order to identify such cell surface molecules, we performed DNA
      microarray analysis using mRNA from fetal hepatocytes in E12.5 and E17.5 mice and
      cDNAs encoding a membrane protein were selected. Northern blot analysis was
      employed to confirm the genes upregulated during maturation of fetal hepatocytes
      and neuritin, a GPI-anchored protein, was found as a membrane protein expressed
      in hepatocytes, but not in nonparenchymal cells. Its expression increased along
      with liver development and the maximum expression was achieved from the neonatal
      to adult stage. The neuritin protein was localized in sinusoidal lumen of
      hepatocytes in adult liver. Partial hepatectomy transiently downregulated the
      expression of neuritin. The expression of neuritin mRNA in C/EBPalpha deficient
      liver was reduced to about 50% of that of wild type mice. Thus, neuritin
      expression is well correlated to the maturation of hepatocytes and can be a
      useful tool to define the differentiation stage of hepatocytes.

PMID- 16081068
TI  - Dietary unripe apple polyphenol inhibits the development of food allergies in
      murine models.
AB  - The incidence of type I allergic disorders has been increasing worldwide,
      particularly, the hypersensitivity to food. We first showed that apple condensed
      tannin (ACT) intake would inhibit the development of the oral sensitization and
      that the inhibition could correlate with the rise in the population of
      TCR(gamma)delta-T cells in the intestinal intraepithelial lymphocytes (IEL) using
      W/W(V) mice and B10A mice which were ovalbumin (OVA)-orally sensitized. Serum OVA
      specific immunoglobulin E and immunoglobulin G1 titers in the OVA-orally
      sensitized W/W(V) and B10A mice ad libitium fed ACT were extremely inhibited
      compared to those of the control. The ACT intakes of OVA-sensitized W/W(V) and
      B10A mice inhibited the immediate reduction of the body temperature or the rise
      in serum histamine induced by active systemic anaphylaxis. The proportions of the
      TCR(gamma)delta-T cells in the IEL of the OVA-orally sensitized W/W(V) and B10A
      mice ad libitium fed ACT were significantly greater than that in the controls.
      Furthermore, ACT feeding by itself could induce the rise in the percentage of the
      TCR(gamma)delta-T cells among the IEL of the W/W(V) and B10A mice. This suggests
      that the ACT intake may prevent the development of food allergies and this effect
      could be correlated with the rise in the percentage of TCR(gamma)delta-T cells
      among the IEL.

PMID- 16081069
TI  - Tobamovirus-resistant tobacco generated by RNA interference directed against host
      genes.
AB  - Two homologous Nicotiana tabacum genes NtTOM1 and NtTOM3 have been identified.
      These genes encode polypeptides with amino acid sequence similarity to
      Arabidopsis thaliana TOM1 and TOM3, which function in parallel to support
      tobamovirus multiplication. Simultaneous RNA interference against NtTOM1 and
      NtTOM3 in N. tabacum resulted in nearly complete inhibition of the multiplication
      of Tomato mosaic virus and other tobamoviruses, but did not affect plant growth
      or the ability of Cucumber mosaic virus to multiply. As TOM1 and TOM3 homologues
      are present in a variety of plant species, their inhibition via RNA interference
      should constitute a useful method for generating tobamovirus-resistant plants.

PMID- 16081070
TI  - STAT4 is a target of the hematopoietic zinc-finger transcription factor Ikaros in
      T cells.
AB  - STAT4 is a transcription factor activated in response to IL-12, and is involved
      in Th1 cell development. The molecular mechanisms controlling the transcription
      of the STAT4 gene are however, unclear. Sequence comparison of the 5' flanking
      regions of human, mouse and pufferfish (Fugu rubripes) Stat4 genes revealed a
      high frequency of Ikaros (Ik) binding elements in all three species. We then
      investigated the role of Ik binding elements in the human STAT4 promoter using
      Jurkat T cells. Transactivation, electrophoretic mobility shift assay and RNA
      interference-mediated gene knockdown experiments revealed that Ik is involved in
      the regulation of STAT4 in human T cells.

PMID- 16081071
TI  - Leukemia inhibitory factor signaling is implicated in embrionic development of
      the HPA axis.
AB  - Leukemia inhibitory factor (LIF) is expressed in the hypothalamic-pituitary
      adrenal (HPA) axis and stimulates pituitary POMC transcription. The role of LIF
      receptor signaling in HPA axis development was examined. Lifr -/- and Lifr +/+
      fetuses were obtained by Cesarean section on E18.5. Despite a 3-fold induction of
      hypothalamic CRH mRNA, pituitary POMC mRNA and RU486-induced ACTH levels were
      decreased in Lifr -/- mice. High CRH may be caused by increased central TNFalpha
      and IL-6 expression. Lifr -/- mice demonstrate elevated pituitary glucocorticoid
      (GR) and mineralocorticoid (MR) receptor mRNA and protein levels, indicating the
      importance of LIF signaling for HPA axis development.

PMID- 16081072
TI  - Silencing of NbECR encoding a putative enoyl-CoA reductase results in
      disorganized membrane structures and epidermal cell ablation in Nicotiana
      benthamiana.
AB  - The very long chain fatty acids (VLCFAs) are synthesized by the microsomal fatty
      acid elongation system in plants. We investigated cellular function of NbECR
      putatively encoding enoyl-CoA reductase that catalyzes the last step of VLCFA
      elongation in Nicotiana benthamiana. Virus-induced gene silencing of NbECR
      produced necrotic lesions with typical cell death symptoms in leaves. In the
      affected tissues, ablation of the epidermal cell layer preceded disintegration of
      the whole leaf cell layers, and disorganized cellular membrane structure was
      evident. The amount of VLCFAs was reduced in the NbECR VIGS lines, suggesting
      NbECR function in elongation of VLCFAs. The results demonstrate that NbECR
      encodes a putative enoyl-CoA reductase and that the NbECR activity is essential
      for membrane biogenesis in N. benthamiana.

PMID- 16081073
TI  - The leucine 10 residue in the pleckstrin homology domain of ceramide kinase is
      crucial for its catalytic activity.
AB  - Ceramide kinase (CERK) converts ceramide (Cer) to ceramide-1-phosphate (C1P), a
      newly recognized bioactive molecule capable of regulating diverse cellular
      functions. The N-terminus of the CERK protein encompasses a sequence motif known
      as a pleckstrin homology (PH) domain. However, little is known regarding the
      functional roles of this domain in CERK. In this study, we have demonstrated that
      the PH domain of CERK is essential for its enzyme activity. Using site-directed
      mutagenesis, we have further determined that Leu10 in the PH domain has an
      important role in CERK activity. Replacing this residue with a neutral alanine or
      isoleucine, caused a dramatic decrease in CERK activity to 1% and 29%,
      respectively, compared to CERK, but had no effect on substrate affinity. The
      study presented here suggests that the PH domain of CERK is not only
      indispensable for its activity but also act as a regulator of CERK activity.

PMID- 16081074
TI  - Recognition of stable protein mutants with 3D stochastic average electrostatic
      potentials.
AB  - As more and more proteins are applied to biochemical research there is increasing
      interest in studying their stability. In this study, a Markov model has been used
      to calculate molecular descriptors of the protein structure and these are called
      the average electrostatic potentials (xi(k)). These descriptors were intended to
      encode indirect electrostatic pair-wise interactions between amino acids located
      at Euclidean distance k within a given 3D protein backbone. The different xi(k)
      values could be calculated for the protein as a whole or for specific protein
      regions (orbits), which include amino acids that lie within a given range of
      distances from the center of charge of the protein. In this work we calculated
      the xi(k) values for 657 mutants of different proteins. A Linear Discriminant
      Analysis model correctly classified a subset of 435 out of 493 proteins according
      to their thermal stability - a level of predictability of 88.2%. This experiment
      was repeated with three additional subsets of proteins selected at random from
      the initial series of 657. More specifically, the model predicted 314/356 (88.2%)
      of mutants with higher stability than the corresponding wild-type protein and
      264/301 (86.7%) of proteins with near wild-type stability. These results
      illustrate the possibilities for the average stochastic potentials xi(k) in the
      study of 3D-structure/property relationships for biochemically relevant proteins.

PMID- 16081075
TI  - PHI-1 induced enhancement of myosin phosphorylation in chicken smooth muscle.
AB  - Herein, we provide evidence that in chicken smooth muscle, G-protein stimulation
      by a Rho-kinase pathway leads to an increase in myosin light chain
      phosphorylation. Additionally, G-protein stimulation did not increase MYPT1
      phosphorylation at Thr695 or Thr850, and CPI-17, was not expressed in chicken
      smooth muscle. However, PHI-1 was present in chicken smooth muscle tissues. Both
      agonist and GTP(gamma)S stimulation result in an increase in PHI-1
      phosphorylation, which is inhibited by inhibitors to both Rho-kinase (Y-27632)
      and (PKC) GF109203x. These data suggest that PHI-1 may act as a CPI-17 analog in
      chicken smooth muscle and inhibit myosin phosphatase activity during G-protein
      stimulation to produce Ca2+ sensitization.

PMID- 16081076
TI  - RNA interference-mediated silencing of the syntaxin 5 gene induces Golgi
      fragmentation but capable of transporting vesicles.
AB  - It has been suggested that syntaxin 5 (Syx5) participates in vesicular transport.
      We examined the effects of Syx5 down-regulation on the morphology of the Golgi
      apparatus and the transport of vesicles in mammalian cells. Knockdown of the Syx5
      gene resulted in Golgi fragmentation without changing the level of endoplasmic
      reticulum (ER)-resident proteins, other Golgi-SNAREs (soluble N-ethylmaleimide
      sensitive factor-attachment protein receptors), and coatmer proteins. Strikingly,
      a major decrease in Syx5 expression barely affected the anterograde transport of
      vesicular stomatitis virus G (VSVG) protein to the plasma membrane. These results
      suggest that Syx5 is required for the maintenance of the Golgi structures but may
      not play a major role in the transport of vesicles carrying VSVG between the ER
      and the Golgi compartment.

PMID- 16081078
TI  - Molecular-scale observation of the surface of polystyrene particles by AFM.
AB  - The surface morphology of polystyrene particles prepared by soap-free emulsion
      polymerization was observed in situ using the tapping mode of an atomic force
      microscope (AFM). Here, the use of a cationic initiator enabled us to synthesize
      positively charged polystyrene, which then adsorbed electrostatically onto the
      negatively charged mica plate with molecular-scale smoothness. The following was
      found from AFM measurements in water. The surface of polystyrene particles
      changed from smooth to rough as the polymerization proceeded in the experimental
      condition, where the bulk generated tiny particles continuously, because of the
      heterocoagulation in the growth process between the newborn and tiny particles
      and the existing particles. However, it is easy to prepare the particles with
      smooth surfaces on the condition of rich monomers because the monomers in the
      bulk dissolve the polymers which form the surface morphology to be deformable and
      reduce the interfacial area.

PMID- 16081079
TI  - Effect of Fenton's reagent on O/W emulsions stabilized by black liquor.
AB  - The effect of Fenton's reagent (FR) on surface and dispersion properties of black
      liquor (BL) was investigated. These properties were compared to those of indulin
      C (IC), a commercial lignin, and egg lecithin (Le). FR was applied at two
      different bulk concentrations of H2O2 (160 and 320 mM). At pH 8, a minimum in
      surface tension for the Fenton treated BL was observed. The dispersant ability of
      BL, IC and Le in oil-in-water (O/W) emulsions was studied by measuring emulsion
      stability and drop size. It was found that the surface activity and emulsifying
      capability of BL were higher than those of IC. The emulsifying capability of Le
      was improved by the FR treatment at low H2O2 concentration.

PMID- 16081080
TI  - Mechanisms of ethyl(hydroxyethyl) cellulose-solid interaction: influence of
      hydrophobic modification.
AB  - Hydroxyethyl cellulose and its hydrophobically modified derivatives are widely
      used in many industrial areas such as pharmaceuticals, cosmetics, textiles, paint
      and mineral industries. However, the interaction mechanisms of these biopolymers
      and solids have not been established. In this work, the interaction mechanism and
      conformation of hydrophobically modified ethyl(hydroxyethyl) cellulose (C(14)
      EHEC) have been investigated using spectroscopic, AFM and allied techniques.
      Comparison was made with corresponding unmodified analogue in order to
      investigate the effects of the hydrophobic modification. Electrokinetic studies
      showed that polysaccharides adsorption decreased the negative zeta potential of
      talc but did not reverse the charge. EHEC adsorption on talc was not found to be
      affected significantly by changes in solution conditions such as pH and ionic
      strength, ruling out electrostatic force as the controlling factor. However, HM
      EHEC adsorption was found to increase markedly with increase in ionic strength
      from 0.1 to 1 suggesting a role for the hydrophobic force in this adsorption
      process. Fluorescence spectroscopic studies conducted to investigate the role of
      hydrophobic bonding using pyrene probe showed no evidence of the formation of
      hydrophobic domains at talc-aqueous interface. Urea, a hydrogen bond breaker,
      reduced the adsorption of HM-EHEC on talc markedly. In FTIR study, the changes in
      the infrared bands, associated with the CO stretch coupled to the CC stretch and
      OH deformation, were significant and therefore support strong hydrogen bonding of
      HM-EHEC on the solid surface. Moreover, Langmuir modeling of the adsorption
      isotherms suggests hydrogen bonding to be a major force for the adsorption of
      EHEC and C(14)-EHEC on solid since the adsorption free energies of these polymers
      were close to that for hydrogen bond formation. All of the above results suggest
      that the main driving force for EHEC adsorption on talc is hydrogen bonding
      rather than electrostatic interaction or hydrophobic force. For hydrophobically
      modified C(14)-EHEC, hydrophobic force plays a synergetic role in adsorption
      along with hydrogen bonding. From computer modeling and AFM imaging, it is
      proposed that C(0)-EHEC and C(14)-EHEC adsorb flat on talc with ethylene oxide
      side chains and hydrophobic groups protruding out from the surface into bulk
      water phase.

PMID- 16081081
TI  - An ATR-FTIR spectroscopic study of the competitive adsorption between oxalate and
      malonate at the water-goethite interface.
AB  - The competitive adsorption between oxalate and malonate at the water-goethite
      interface was studied as a function of pH and total ligand concentrations by
      means of quantitative adsorption measurements and attenuated total reflectance
      Fourier transform infrared (ATR-FTIR) spectroscopy. The results obtained show
      that ATR-FTIR spectroscopy resolves the individual spectroscopic features of
      oxalate and malonate when adsorbed simultaneously at the water-goethite
      interface. The characteristic peaks of all four types of predominating surface
      complexes existing in the single ligand systems were identified, namely one inner
      sphere and one outer sphere surface complex for each ligand. The quantitative
      adsorption data showed that oxalate partially out-competes malonate at the water
      goethite interface. Evaluation of the peak area variations as a function of pH
      indicated that the stronger oxalate adsorption can be ascribed to the more stable
      inner sphere surface complex of oxalate, which in turn is related to the oxalate
      five-member chelate ring structure yielding a more stable complex compared to the
      six-member ring of malonate.

PMID- 16081082
TI  - Transport coefficients and orientational distributions of rodlike particles with
      magnetic moment normal to the particle axis under circumstances of a simple shear
      flow.
AB  - We have investigated the influences of the magnetic field strength, shear rate,
      and random forces on transport coefficients such as viscosity and diffusion
      coefficient, and also on the orientational distributions of rodlike particles of
      a dilute colloidal dispersion. This dispersion is composed of ferromagnetic
      spheroidal particles with a magnetic moment normal to the particle axis. In the
      present analysis, these spheroidal particles are assumed to conduct the
      rotational Brownian motion in a simple shear flow as well as an external magnetic
      field. The basic equation of the orientational distribution function has been
      derived from the balance of the torques and solved numerically. The results
      obtained here are summarized as follows. For a very strong magnetic field, the
      rodlike particle is significantly restricted in the field direction, so that the
      particle points to a direction normal to the flow direction (and also to the
      magnetic field direction). However, the present particle does not exhibit a
      strong directional characteristic, which is one of the typical properties for the
      previous particle with a magnetic moment parallel to the particle axis. That is,
      the particle can rotate around the axis of the magnetic moment, although the
      magnetic moment nearly points to the field direction. The viscosity significantly
      increases with the field strength, as in the previous particle model. The
      particle of a larger aspect ratio leads to the larger increase in the viscosity,
      since such elongated particles induce larger resistance in a flow field. The
      diffusion coefficient under circumstances of an applied magnetic field is in
      reasonable agreement between theoretical and experimental results.

PMID- 16081083
TI  - Characterization of the flow of anisotropic colloidal particles using energy
      dispersive X-ray diffraction.
AB  - The technique of energy-dispersive X-ray diffraction to study the orientation of
      microscopic crystalline particles dispersed in a liquid has been described
      recently. This complements previous neutron diffraction studies by permitting
      measurements at higher spatial resolution. Work with synchrotron radiation and
      high-energy X-rays has allowed studies on liquid dispersions flowing in pipes
      with a thickness of about 1 cm and a spatial resolution of 100 mum. Kaolinite is
      often found as a dispersion of monocrystalline, microscopic plates. The
      crystallographic layer structure is commensurate with the particle shape: the 00l
      direction is normal to the plane of the plates. Measurements of diffraction of
      the flowing liquid dispersion in a pipe oriented in various directions to the
      incident beam can be used to deduce the average orientation and order parameters
      of the particles. The competing effects of alignment with walls and in flow
      fields were observed. Further work has measured the orientation near a bend in a
      pipe.

PMID- 16081084
TI  - Comparative modelling of mono- and dinitrophenols sorption on yellow bentonite
      from aqueous solutions.
AB  - Equilibrium removal of three substituted nitrophenols, namely 2-nitrophenol (2
      NP), 4-nitrophenol (4-NP), and 2,4-dinitrophenol (2,4-DNP), by adsorption on
      yellow bentonite was tested. The batch kinetic data are described by the pseudo
      first order, pseudo-second order, and intraparticle diffusion models. Results
      show that chemisorption processes could be rate limiting in the sorption step.
      The adsorption equilibrium was modelled by the Langmuir and Freundlich equations.
      The Langmuir model better represents the equilibrium isotherm data for 2-NP, 4
      NP, and 2,4-DNP uptake on yellow bentonite. 4-NP is adsorbed in larger amounts
      than the disubstituted nitrophenol. Uptake of nitrophenols increases in the order
      2-NP < 2,4-DNP < 4-NP.

PMID- 16081085
TI  - Time dependency and irreversibility of water desorption by drinking-water
      treatment residuals: implications for sorption mechanisms.
AB  - Drinking-water treatment residuals (WTRs) are being evaluated as cost-effective
      sorption media for use in environmental remediation. Data from previous work have
      suggested that intraparticle phosphorus (P) diffusion into micropores is the rate
      limiting mechanism of P sorption by WTRs. We used isothermal thermogravimetric
      analysis (TG) to study water desorption/resorption dynamics as they relate to
      steric diffusion rate limitations for prospective sorbates. Results showed that
      air-dried WTR particles contain significant amounts of water. Only about 40% of
      water desorbed isothermally (70 degrees C) for 10 h was readsorbed when particles
      were reexposed to ambient temperature and moisture conditions. This hysteresis
      related closely with time dependency of water loss, suggesting steric diffusional
      hindrance of water re-adsorption by meso- and micropores. The irreversibly
      desorbed water may be the component requiring increased kinetic energy to
      overcome diffusional resistance. Another possible factor in irreversibility could
      be pore shrinkage. Samples incubated for 12 months at 70 degrees C prior to TG
      analysis showed no hysteresis at 70 degrees C. Isothermal water losses with time
      fit well (r2 = 0.95) the diffusion model of Kabai. These results are consistent
      with an aqueous pore network that would account for high phosphorus sorption
      capacity and hysteresis that has been recently documented for WTRs.

PMID- 16081086
TI  - Influence of pore structure and pretreatments of activated carbons and water
      effects on breakthrough dynamics of tert-butylbenzene.
AB  - Several activated carbons differently pretreated (de-ashed, oxidized, reduced,
      wetted, frozen, and dried) were investigated using static (equilibrium adsorption
      of nitrogen and benzene) and dynamic (tert-butylbenzene (TBB)) adsorption
      methods. Treatments of carbons at relatively mild conditions leading to not great
      changes in their textural characteristics affect the TBB breakthrough
      concentration because of changes in the chemistry of the surfaces (oxidized or
      reduced) and the presence of water in airstream or pre-adsorbed on carbon beds.
      Oxygen-containing functionalities at a carbon surface change condition of
      competitive adsorption of nonpolar TBB and polar water molecules. Calculations of
      distribution functions of adsorption potential (A), energy (E), Gibbs free energy
      (Delta G) of adsorption of benzene and TBB and effective adsorption (first-order)
      rate pseudoconstant beta e over different ranges of relative exit TBB
      concentration c(t)/c(0) (from approximately 10(-5) to 0.01-0.4) reveal nonlinear
      effects caused by the size of carbon granules, the pore size distributions, the
      presence of water, oxidation or reduction of the surfaces and other treatments
      resulting in distribution functions f(y) with nonzero intensity in relatively
      broad ranges of the A, E, Delta G, and beta e values. There are many factors
      affecting the breakthrough parameters; therefore, simple linear relationships
      between these parameters and the structural characteristics (S(BET), S(DS), Vp,
      and V(DS)) are not observed.

PMID- 16081087
TI  - Modeling solubilization of oil mixtures in anionic microemulsions II. Mixtures of
      polar and non-polar oils.
AB  - Polar/amphiphilic oils, called lipophilic linkers, are sometimes added to oil
      water-ionic surfactant microemulsions in order to increase the solubilization of
      hydrophobic oils. The solubilization increase has been well documented for a
      number of systems. However, mathematical models to calculate the solubilization
      increase have been proposed only for optimum microemulsions (i.e., middle phase
      microemulsions solubilizing equal volumes of oil and water). In this paper we
      propose a model, which predicts solubilization enhancement for non-optimum
      microemulsion systems as well. The model is an extension of the net-average
      curvature model of microemulsion. The net-average curvature model is combined
      with a surface activity model to account for the increased palisade layer
      solubilization due to the presence of the polar/amphiphilic oil component. New
      non-linear mixing rules are also incorporated to account for the optimum salinity
      and the characteristic length variation of the anionic surfactant microemulsion
      as a function of the lipophilic linker concentration. The model predicts the
      effect of the lipophilic linker and the electrolyte concentration on the oil
      solubilization in accordance with the experimental results.

PMID- 16081088
TI  - Destabilization of polystyrene latex particles induced by adsorption of
      polyvinylamine: mass, size and structure characteristics of the growing
      aggregates.
AB  - The obviously visible aggregation of suspended colloidal particles resulting from
      the addition of polyvinylamine to the aqueous dispersion of polystyrene latex
      particles bearing surface sulfate groups set in with a delay of 24 h. The
      aggregation mechanisms and the fractal dimension of the aggregates were derived
      from the variations with time of the weight and number averaged masses of the
      aggregates as well as of the weight averaged harmonic mean diameter of the size
      distribution. Since the establishment of starved layers was determined to be
      relatively fast and to leave the liquid phase free of polymer, the delay for the
      obvious destabilization was attributed to the reconformation of adsorbed
      macromolecules that was expected to be extremely slow. This reconformation
      promoted the emergence of the diffusion-limited aggregation process that
      accompanies the permanent reaction-limited aggregation process. The fractal
      dimension of the latex particles/polyvinylamine aggregates was determined to be
      2.12.

PMID- 16081089
TI  - Strain hardening and fracture of heat-set fractal globular protein gels.
AB  - Non-linear mechanical behavior at large shear deformation was been investigated
      for heat-set beta-lactoglobulin gels at pH 7 and 0.1 M NaCl using both
      oscillatory shear and shear flow. These gels have a self-similar structure at
      length scales smaller than the correlation length of the gel with fractal
      dimension d(f)=2. Strain hardening is observed that can be well described using
      the model proposed by Gisler et al. [T.C. Gisler, R.C. Ball, D.A. Weitz, Phys.
      Rev. Let. 82 (1999) 1064] for fractal colloidal gels. The increase of the shear
      modulus normalized by the low strain value (G(0)) is independent of G(0). For
      weak gels the elasticity increases up to a factor of ten, while for strong gels
      the increase is very small. At higher deformation irreversible fracture occurs,
      which leads eventually to macroscopic failure of the gel. For weak gels formed at
      low concentrations the deformation at failure is about 2, independent of the
      shear modulus. For strong gels fracture occurs at approximately constant stress
      (2 x 10(3) Pa).

PMID- 16081090
TI  - Surface characterisation of plasma-modified poly(ethylene terephthalate).
AB  - This paper reports the modifications produced by nitrogen and helium cold plasmas
      on the surface of PET. The changes have been studied by diffuse reflectance
      Fourier transform spectroscopy (DRIFTS), atomic force microscopy (AFM) and
      inverse gas-solid chromatography (IGSC). Nitrogen and oxygen atoms seem to appear
      on the surface of PET as a consequence of the exposure to the atmosphere after
      the treatments with plasmas. AFM shows that both plasmas altered in different
      extent the surface of PET as they break the polymer chains producing low
      molecular products which appear as bumps on the surface. The surface area and the
      porosity of PET does not change by plasma treatments even after 15 min. The
      dispersive component of the surface free energy, gamma(s)(d), decreases after
      long treatments with nitrogen plasma whereas it remains almost unchanged after
      long treatment with helium plasma.

PMID- 16081091
TI  - Gradations of emulation learning in infants' imitation of actions on objects.
AB  - This study explored different gradations of emulation in the imitation of actions
      on objects by 17-month-olds. Experiment 1 established levels of behavioral
      reproduction following prerecorded video demonstrations similar to those levels
      following live demonstrations. In Experiment 2, two digitally modified videos,
      where object movements or body movements critical to producing the target action
      were highlighted in isolation, were developed. Infants produced the target action
      equally frequently by observing the object movement video and observing the
      unmodified video. In contrast, their performance was much less successful based
      on the body movement video. In Experiment 3, the performance obtained following
      the object movement video was similar to that following a further video that
      emphasized the object movements produced in unsuccessful attempts to produce the
      target action. These findings suggest that emulation in the form of object
      movement reenactment or affordance learning plays a role in the social learning
      of actions on objects during infancy.

PMID- 16081092
TI  - Endocrine changes in maturing primary queens of Zootermopsis angusticollis.
AB  - Termite queens are highly specialized for reproduction, but little is known about
      the endocrine mechanisms regulating this ability. We studied changes in the
      endocrinology and ovarian maturation in primary reproductive females of the
      dampwood termite Zootermopsis angusticollis following their release from
      inhibitory stimuli produced by mature queens. Winged alates were removed from
      their natal nest, manually dewinged, then paired in an isolated nest with a
      reproductive male. Development was tracked by monitoring ovarian development, in
      vitro rates of juvenile hormone (JH) production by corpora allata, and hemolymph
      titers of JH and ecdysteroids. The production rate and titer of JH were
      positively correlated with each other but negatively correlated with ecdysteroid
      titer. Four days after disinhibition, JH release and titer decreased while
      ecdysteroid titer increased. The new levels persisted until day 30, after which
      JH increased and ecdysteroids decreased. Fully mature queens had the highest
      rates of JH production, the lowest ecdysteroid titers, and the greatest number of
      functional ovarioles. The results support the hypothesis that JH plays a dual
      role in termite queens depending on their stage of development; an elevated JH
      titer in immature alates may maintain reproductive inhibition, but an elevated JH
      titer in mature queens may stimulate ovarian activity. The decline in JH
      production and the elevation in ecdysteroid titer correspond to a period of
      physiological reorganization and activation. The specific function of
      ecdysteroids is unknown but they may help to modulate the activity of the corpora
      allata.

PMID- 16081093
TI  - Manganese superoxide dismutase from Biomphalaria glabrata.
AB  - The investigation of the response of Biomphalaria glabrata snails to Echinostoma
      paraensei (digenea) at 2 days post-exposure by suppression subtractive
      hybridization yielded a partial sequence of the anti-oxidant enzyme manganese
      superoxide dismutase (MnSOD). Full-length MnSOD (669nt) from M line and BS-90
      strains of B. glabrata differed by one synonymous nucleotide replacement. B.
      glabrata has 1-4 MnSOD loci (Southern hybridization). Both snail strains
      expressed MnSOD at equal baseline levels (quantitative PCR). Susceptible snails
      increased expression of MnSOD following infection with E. paraensei or
      Schistosoma mansoni, and expression was reduced in the incompatible combination
      (BS-90 B. glabrata and S. mansoni). Thus, MnSOD did not determine resistance or
      susceptibility for these parasites, but expression of MnSOD is consistent with
      its involvement in a stress response of B. glabrata.

PMID- 16081094
TI  - Comparison of the bacterial Enhancin-like proteins from Yersinia and Bacillus
      spp. with a baculovirus Enhancin.
AB  - Enhancins are a class of metalloproteases found in some baculoviruses that
      enhance viral infection by degrading the peritrophic membrane (PM) of the insect
      midgut. However, sequencing has revealed enhancin-like genes with 24-25% homology
      to viral enhancins, in the genomes of Yersinia pestis and Bacillus anthracis.
      AcMNPV does not encode enhancin therefore recombinant AcMNPV budded viruses (BVs)
      and polyhedra inclusion bodies (PIBs) were generated expressing the bacterial
      Enhancins. Bacterial Enhancins were found to be cytotoxic when compared to viral
      enhancin, however, larval bioassays suggested that the bacterial Enhancins did
      not enhance infection in the same way as viral Enhancin. This suggests that the
      bacterial Enhancins may have evolved a distinct biochemical function.

PMID- 16081095
TI  - A structural basis for depolymerization of alginate by polysaccharide lyase
      family-7.
AB  - Alginate lyases depolymerize alginate, a heteropolysaccharide consisting of alpha
      L-guluronate and beta-D-mannuronate, through a beta-elimination reaction. Their
      structure/function relationships are expected to provide information valuable to
      future industrial alginate processing and drug design for Pseudomonas aeruginosa
      alginate biofilm-dependent infection, but much remains unknown. Here, we present
      the crystal structure at 1.0 A resolution and the results of mutational analysis
      of Sphingomonas sp. A1 alginate lyase A1-II', which is grouped into the
      polysaccharide lyase (PL) family-7. The overall structure of A1-II' uses a beta
      sandwich fold, and it has a large active cleft covered by two short flexible
      loops. Comparison with other family PL-7 structures indicated that loop opening
      is necessary for substrate binding when the catalytic reaction is initiated. In
      contrast to the disorder in many side-chains on the protein surface, the three
      adjacent beta-strands at the center of the active cleft are well ordered. This
      results from hydrogen bond networks and stacking-like associations identical with
      those in other family PL-7 structures. Disruption of these interactions by site
      directed mutagenesis (R146A, E148A, R150A, Q189A, and K280A) makes the protein
      insoluble or greatly decreases its activity. The A1-II' structure includes two
      sulfate ions in the active cleft. Ammonium sulfate was a potent inhibitor with a
      Ki of 2.5 mM, indicating that our structure represents a model of the inhibitory
      state. Results of mutational analysis and continuous hydrogen bond networks
      suggest that Arg146, Gln189, His191, and Tyr284 form an active center. Tyr284OH
      appears particularly crucial to the catalytic reaction, which is supported by
      sulfate ion binding and the proximity to the C5 and O4 atoms of subsite +1 in the
      model obtained by energy minimization calculations using tri-mannuronate. The
      structural basis shown by this study is similar in many respects to that of the
      family PL-5 enzymes.

PMID- 16081096
TI  - Role of the fetal and alpha/beta exons in the function of fast skeletal troponin
      T isoforms: correlation with altered Ca2+ regulation associated with development.
AB  - In mammalian fast skeletal muscle, constitutive and alternative splicing from a
      single troponin T (TnT) gene produce multiple developmentally regulated and
      tissue specific TnT isoforms. Two exons, alpha (exon 16) and beta (exon 17),
      located near the 3' end of the gene and coding for two different 14 amino acid
      residue peptides are spliced in a mutually exclusive manner giving rise to the
      adult TnTalpha and the fetal TnTbeta isoforms. In addition, an acidic peptide
      coded by a fetal (f) exon located between exons 8 and 9 near the 5' end of the
      gene, is specifically present in TnTbeta and absent in the adult isoforms. To
      define the functional role of the f and alpha/beta exons, we constructed
      combinations of TnT cDNAs from a single human fetal fast skeletal TnTbeta cDNA
      clone in order to circumvent the problem of N-terminal sequence heterogeneity
      present in wild-type TnT isoforms, irrespective of the stage of development.
      Nucleotide sequences of these constructs, viz. TnTalpha, TnTalpha + f, TnTbeta -
      f and TnTbeta are identical, except for the presence or absence of the alpha or
      beta and f exons. Our results, using the recombinant TnT isoforms in different
      functional in vitro assays, show that the presence of the f peptide in the N
      terminal T1 region of TnT, has a strong inhibitory effect on binary interactions
      between TnT and other thin filament proteins, TnI, TnC and Tm. The presence of
      the f peptide led to reduced Ca2+-dependent ATPase activity in a reconstituted
      thin filament, whereas the contribution of the alpha and beta peptides in the
      biological activity of TnT was primarily modulatory. These results indicate that
      the f peptide confers an inhibitory effect on the biological function of fast
      skeletal TnT and this can be correlated with changes in the Ca2+ regulation
      associated with development in fast skeletal muscle.

PMID- 16081097
TI  - The 100K-chaperone protein from adenovirus serotype 2 (Subgroup C) assists in
      trimerization and nuclear localization of hexons from subgroups C and B
      adenoviruses.
AB  - Recombinant hexons from subgroup C adenoviruses (Ad2 and Ad5) and from a member
      of subgroup B (Ad3) adenoviruses have been expressed in insect cells. When
      expressed alone, all three hexons were found to be insoluble and accumulated as
      inclusion bodies in the cytoplasm. However, co-expression of recombinant Ad2, Ad5
      or Ad3 hexon with Ad2 L4-100K protein resulted in the formation of soluble
      trimeric hexons. EM analysis of hexons revealed that they were indistinguishable
      from native hexon capsomers isolated from Ad2-infected human cells, or released
      from partially disrupted adenovirions. This suggests that 100K acts as a
      chaperone for hexon folding and self-assembly into capsomer in insect cells.
      Since 100K protein assists in the trimerization of subgroup C hexon, and of
      subgroup B hexon protein, it implies that it functions in a manner that is both
      homo- and heterotypic. During the course of recombinant protein expression, the
      100K protein was found in association with hexon monomers and trimers within the
      cytoplasm. In the nucleus, however, 100K was found in complexes with hexon
      trimers exclusively. EM observation of purified 100K protein samples showed a
      dumb-bell-shaped molecule compatible with a monomeric protein. EM analysis of
      hexon-100K protein complexes showed that interaction of hexon with the 100K
      protein occurred via one of the globular domains of the 100K protein molecule.
      Our data confirm the role of the 100K protein as a scaffold protein for hexon,
      and provide evidence suggesting its function in hexon nuclear import in insect
      cells.

PMID- 16081098
TI  - Structural insights into drug processing by human carboxylesterase 1: tamoxifen,
      mevastatin, and inhibition by benzil.
AB  - Human carboxylesterase 1 (hCE1) exhibits broad substrate specificity and is
      involved in xenobiotic processing and endobiotic metabolism. We present and
      analyze crystal structures of hCE1 in complexes with the cholesterol-lowering
      drug mevastatin, the breast cancer drug tamoxifen, the fatty acyl ethyl ester
      (FAEE) analogue ethyl acetate, and the novel hCE1 inhibitor benzil. We find that
      mevastatin does not appear to be a substrate for hCE1, and instead acts as a
      partially non-competitive inhibitor of the enzyme. Similarly, we show that
      tamoxifen is a low micromolar, partially non-competitive inhibitor of hCE1.
      Further, we describe the structural basis for the inhibition of hCE1 by the
      nanomolar-affinity dione benzil, which acts by forming both covalent and non
      covalent complexes with the enzyme. Our results provide detailed insights into
      the catalytic and non-catalytic processing of small molecules by hCE1, and
      suggest that the efficacy of clinical drugs may be modulated by targeted hCE1
      inhibitors.

PMID- 16081099
TI  - Site-specific reflex response of ubiquitin to loop insertions.
AB  - Predicting the structural effects of insertions in proteins by homology modeling
      remains a challenge. To investigate the molecular basis for conformational
      adaptations to insertions, ten mutants of ubiquitin were generated by introducing
      five different inserts, varying from five to 11 residues in size, at two
      different sites. Most insertion sequences were derived from homologous positions
      in structurally homologous ubiquitin-like proteins; to test sequence specificity,
      insertions were made into both homologous and non-homologous sites in ubiquitin.
      Structural inferences from NMR data suggest that each insertion site shows a
      reflex response to insertions: the sequence of the insertion has much less impact
      on structural adaptations than does the site of the insertion. Further, each site
      responds to insertions in a unique but consistent manner. For a given insertion
      site, different inserted sequences give rise to different stabilities, but the
      relationship between stability and sequence is not yet clear. However, the change
      in stability is similar for all insertions in a given site.

PMID- 16081100
TI  - Structural evidence of a passive base-flipping mechanism for AGT, an unusual GT-B
      glycosyltransferase.
AB  - The Escherichia coli T4 bacteriophage uses two glycosyltransferases to
      glucosylate and thus protect its DNA: the retaining alpha-glucosyltransferase
      (AGT) and the inverting beta-glucosyltransferase (BGT). They glucosylate 5
      hydroxymethyl cytosine (5-HMC) bases of duplex DNA using UDP-glucose as the sugar
      donor to form an alpha-glucosidic linkage and a beta-glucosidic linkage,
      respectively. Five structures of AGT have been determined: a binary complex with
      the UDP product and four ternary complexes with UDP or UDP-glucose and
      oligonucleotides containing an A:G, HMU:G (hydroxymethyl uracyl) or AP:G
      (apurinic/apyrimidinic) mismatch at the target base-pair. AGT adopts the GT-B
      fold, one of the two folds known for GTs. However, while the sugar donor binding
      mode is classical for a GT-B enzyme, the sugar acceptor binding mode is
      unexpected and breaks the established consensus: AGT is the first GT-B enzyme
      that predominantly binds both the sugar donor and acceptor to the C-terminal
      domain. Its active site pocket is highly similar to four retaining GT-B
      glycosyltransferases (trehalose-6-phosphate synthase, glycogen synthase, glycogen
      and maltodextrin phosphorylases) strongly suggesting a common evolutionary origin
      and catalytic mechanism for these enzymes. Structure-guided mutagenesis and
      kinetic analysis do not permit identification of a nucleophile residue
      responsible for a glycosyl-enzyme intermediate for the classical double
      displacement mechanism. Interestingly, the DNA structures reveal partially
      flipped-out bases. They provide evidence for a passive role of AGT in the base
      flipping mechanism and for its specific recognition of the acceptor base.

PMID- 16081101
TI  - RNase E cleavage in the 5' leader of a tRNA precursor.
AB  - In this study, we have used various tRNA(Tyr)Su3 precursor (pSu3) derivatives
      that are processed less efficiently by RNase P to investigate if the 5' leader is
      a target for RNase E. We present data that suggest that RNase E cleaves the 5'
      leader of pSu3 both in vivo and in vitro. The site of cleavage in the 5' leader
      corresponds to the cleavage site for a previously identified endonuclease
      activity referred to as RNase P2/O. Thus, our findings suggest that RNase P2/O
      and RNase E activities are of the same origin. These data are in keeping with the
      suggestion that the structure of the 5' leader influences tRNA expression by
      affecting tRNA processing and indicate the involvement of RNase E in the
      regulation of cellular tRNA levels.

PMID- 16081102
TI  - A three-dimensional cryo-electron microscopy structure of the bacteriophage phiKZ
      head.
AB  - The three-dimensional structure of the Pseudomonas aeruginosa bacteriophage phiKZ
      head has been determined by cryo-electron microscopy and image reconstruction to
      18A resolution. The head has icosahedral symmetry measuring 1455 A in diameter
      along 5-fold axes and a unique portal vertex to which is attached an
      approximately 1800 A-long contractile tail. The 65 kDa major capsid protein,
      gp120, is organized into a surface lattice of hexamers, with T = 27
      triangulation. The shape and size of the hexamers is similar to the hexameric
      building blocks of the bacteriophages T4, phi29, P22, and HK97. Pentameric
      vertices of the capsid are occupied by complexes composed of several special
      vertex proteins. The double-stranded genomic DNA is packaged into a highly
      condensed series of layers, separated by 24 A, that follow the contour of the
      inner wall of the capsid.

PMID- 16081103
TI  - Structure of the conserved cytoplasmic C-terminal domain of occludin:
      identification of the ZO-1 binding surface.
AB  - Occludin is a transmembrane protein localized at tight junctions whose functions
      are complex yet poorly understood. Current evidence supports a role for occludin
      in both the formation of the paracellular barrier and in cell signaling. While
      the N-terminal extracellular domains of occludin mediate homotypic adhesion, the
      distal C-terminal cytoplasmic domain of occludin controls protein targeting and
      endocytosis. The C terminus can also bind to the scaffolding proteins ZO-1, ZO-2,
      ZO-3, cingulin, the membrane trafficking protein VAP33, and the cytoskeletal
      protein F-actin, suggesting an important role for this domain. This domain is
      highly homologous to an important functional domain in the C terminus of the ELL
      family of RNA polymerase II transcription factors. To explore the function of
      occludin, we determined the high-resolution crystal structure of its C-terminal
      distal cytoplasmic domain. The structure comprises three helices that form two
      separate anti-parallel coiled-coils and a loop that packs tightly against one of
      the coiled-coils. Using in vitro binding studies and site-directed mutagenesis,
      we have identified a large positively charged surface that contains the binding
      site for ZO-1, and this surface is required for proper localization of occludin
      to cell-cell junctions. On the basis of sequence conservation, we predict that
      occludin domains from different species and the C-terminal domain of the ELL
      transcription factors share a very similar structure. Our results provide a model
      to further test the function of occludin and its binding to other proteins.

PMID- 16081104
TI  - Caenorhabditis elegans neprilysin NEP-1: an effector of locomotion and pharyngeal
      pumping.
AB  - The control of signal peptide activity by cell surface proteases is one of the
      main factors that regulate the development and behaviour of organisms. In
      mammals, neprilysins (NEPs) are known to play a key role in these processes and
      their inactivation can initiate cellular disorganisation, which in turn may lead
      to prostate cancer or Hirschsprung disease. Although the proteome of the nematode
      Caenorhabditis elegans has been intensively studied, very little is known about
      the function of neprilysins. ZK20.6 (NEP-1), the C.elegans protein with highest
      identity to mammalian neprilysins, is a 753 amino acid residue protein that
      displays all neprilysin-typical characteristics, including a short intracellular
      domain, a transmembrane domain and a long extracellular active domain. Here we
      show that the expression pattern of nep-1 is limited to pharyngeal cells and a
      single head neuron. Compared to wild-type, the locomotion of nep-1 knockout
      animals is significantly impaired, a phenotype that can be rescued by the
      extrachromosomal re-introduction of nep-1. This suggests that this enzyme plays
      an important role in the regulation of nematode locomotion. Finally,
      electrophysiological recording of the pharyngeal activity showed a high
      sensitivity of the nep-1 pharynx to serotonin (5-HT) and to the neuropeptide AF1
      (C.elegans FLP-8), indicating that NEP-1 is a central component that controls the
      neuronal innervation of pharyngeal pumping in C.elegans.

PMID- 16081105
TI  - CSF monoamine patterns in pathological gamblers and healthy controls.
AB  - Previous reports on compounds in the cerebrospinal fluid (CSF) of pathological
      gamblers have focused on disturbed NA, DA and 5-HT function in the central
      nervous system. We have analysed precursors, transmitters and transmitter
      metabolites in 3 x 6 ml of CSF obtained from one female and 11 male pathological
      gamblers and 11 healthy male controls lumbar punctured at the L4-5 level after 8
      h of fasting without preceding strict bedrest. Pathological gamblers displayed
      lower CSF levels of tryptophan and 5-HT while the opposite was the case for 5
      HIAA, tyrosine, DA, HVA, DOPAC and HMPG. In contrast to previous studies, the NA
      level did not differ between pathological gamblers and healthy controls. A
      disrupted CSF gradient was noted for tryptophan, 5-HT, DA, HVA, DOPAC, NA and
      HMPG, but only in pathological gamblers. A disrupted gradient was found for 5
      HIAA in both pathological gamblers and healthy controls. The results are in line
      with the presence of altered indoleamine and catecholamine function in
      pathological gamblers as well as an altered CSF transport from the brain to the
      lumbar compartment in such gamblers.

PMID- 16081106
TI  - Adjunctive herbal medicine with carbamazepine for bipolar disorders: A double
      blind, randomized, placebo-controlled study.
AB  - Chinese herbal medicines possess the therapeutic potential for mood disorders.
      This double-blind, randomized, placebo-controlled study was designed to evaluate
      the efficacy and side effects of the herbal medicine called Free and Easy
      Wanderer Plus (FEWP) as an adjunct to carbamazepine (CBZ) in patients with
      bipolar disorders. One hundred and twenty-four bipolar depressed and 111 manic
      patients were randomized to treatment with CBZ alone, CBZ plus FEWP, or
      equivalent placebo for 12 weeks. CBZ was initiated at 300mg/day and FEWP was
      given at a fixed dose of 36g/day. Efficacy measures included the Hamilton Rating
      Scale for Depression, Montgomery-Asberg Depression Rating Scale , Young Mania
      Rating Scale, Bech-Rafaelsen Mania Scale, and Clinical Global Impression-Severity
      (CGI-S). CBZ monotherapy produced significantly greater improvement on manic
      measures at week 2 through endpoint and CGI-S of depression at endpoint compared
      to placebo. CBZ monotherapy also yielded significantly higher clinical response
      rates than placebo on bipolar depression (63.8% vs. 34.8%, p=0.044) and mania
      (87.8% vs. 57.1%, p=0.012). Compared to CBZ monotherapy, adjunctive FEWP with CBZ
      resulted in significantly better outcomes on the three measures of depression at
      week 4 and week 8 and significantly greater clinical response rate in depressed
      subjects (84.8% vs. 63.8%, p=0.032), but failed to produce significantly greater
      improvement on manic measures and the response rate in manic subjects. There was
      a lesser incidence of dizziness and fatigue in the combination therapy compared
      to CBZ monotherapy. These results suggest that adjunctive FEWP has additive
      beneficial effects in bipolar patients, particularly for those in depressive
      phase.

PMID- 16081107
TI  - A new method to model change in cutaneous blood flow due to mechanical skin
      irritation part I: comparison between experimental and numerical data.
AB  - Mechanical skin irritation creates vasodilation. Vasodilation of vascular
      networks induces increase in blood volume and blood velocity. Both can be
      measured by Laser Doppler Velocimetry. We propose in this article a method
      permitting comparison between experimental and numerical results. Experimental
      data was obtained by Laser Doppler Velocimetry. Numerical results were obtained
      by a continuous model of the vascular network. The model consists of three
      layers. First and last layer are described by anisotropic and heterogeneous
      porous media. They represent the irrigation and the drainage of the vascular
      system. The intermediate layer is described by a lumped parameter model that does
      not permit horizontal fluxes. All vessels are compliant. The permeabilities
      depend on the volumes of the specific layer. Skin irritation is modeled by a
      change in compliance of small arterial blood vessels. The comparison between
      experimental and numerical data is based on the model proposed by Bonner and
      Nossal [1981. Model for laser Doppler measurements of blood flow. Appl. Opt. 20,
      2097-2107]. The model describes the Doppler frequency spectrum S(omega) as a
      function of the optical phenomena creating the frequency shift. The comparison is
      based on the model of the first moment M1 approximately
      integralomegaS(omega)domega. The variables of the first moment can be determined
      by results of the numerical model. We have shown, that it exists a linear
      relation between the change in compliance and the following increase in first
      moment. Using this linear relation experimental and numerical data can be
      compared.

PMID- 16081108
TI  - Evolutionary game theory in an agent-based brain tumor model: exploring the
      'Genotype-Phenotype' link.
AB  - To investigate the genotype-phenotype link in a polyclonal cancer cell
      population, here we introduce evolutionary game theory into our previously
      developed agent-based brain tumor model. We model the heterogeneous cell
      population as a mixture of two distinct genotypes: the more proliferative Type A
      and the more migratory Type B. Our agent-based simulations reveal a phase
      transition in the tumor's velocity of spatial expansion linking the tumor fitness
      to genotypic composition. Specifically, velocity initially falls as rising
      payoffs reward the interactions among the more stationary Type A cells, but
      unexpectedly accelerates again when these A-A payoffs increase even further. At
      this latter accelerating stage, fewer migratory Type B cells appear to confer a
      competitive advantage in terms of the tumor's spatial aggression over the overall
      numerically dominating Type A cells, which in turn leads to an acceleration of
      the overall tumor dynamics while its surface roughness declines. We discuss
      potential implications of our findings for cancer research.

PMID- 16081109
TI  - Cloning and expression of alpha class glutathione S-transferase gene from the
      small hermaphroditic fish Rivulus marmoratus (Cyprinodontiformes, Rivulidae).
AB  - In order to assess its potential as a biomarker of aquatic pollution, an alpha
      class glutathione S-transferase gene (GSTalpha gene) was cloned from the small
      hermaphroditic fish Rivulus marmoratus. The R. marmoratus GSTalpha gene spanned
      1.3 kb, consisting of 6 exons encoding 221 amino acid residues. It showed high
      similarity to zebrafish GST. We named this R. marmoratus GSTalpha gene as rm
      GSTalpha. The cDNA of the rm-GSTalpha gene was also investigated for its
      phylogeny, tissue-specific and chemical-induced expression. Rm-GSTalpha was
      subcloned into a 6 x His-tagged pCRT7 TOPO TA expression vector to produce the
      recombinant 6 x His-tagged rm-GST protein. This will be used in future to raise
      an rm-GSTalpha antibody for use in the study of phase II metabolism involved in
      detoxification. We also exposed R. marmoratus to 300 microg/l of 4-nonylphenol in
      water, and found approximately 4-fold induction of R. marmoratus GSTalpha mRNA in
      the treated animals. In this paper, we discuss the characteristics of the R.
      marmoratus GSTalpha gene as well as its potential use in relation to
      environmental pollution.

PMID- 16081110
TI  - Modulation of oxidative mutagenesis and carcinogenesis by polymorphic forms of
      human DNA repair enzymes.
AB  - Chromosome DNA is continuously exposed to various endogenous and exogenous
      mutagens. Among them, oxidation is one of the most common threats to genetic
      stability, and multiple DNA repair enzymes protect chromosome DNA from the
      oxidative damage. In Escherichia coli, three repair enzymes synergistically
      reduce the mutagenicity of oxidized base 8-hydroxy-guanine (8-OH-G). MutM DNA
      glycosylase excises 8-OH-G from 8-OH-G:C pairs in DNA and MutY DNA glycosylase
      removes adenine incorporated opposite template 8-OH-G during DNA replication.
      MutT hydrolyzes 8-OH-dGTP to 8-OH-dGMP in dNTP pool, thereby reducing the chance
      of misincorporation of 8-OH-dGTP by DNA polymerases. Simultaneous inactivation of
      MutM and MutY dramatically increases the frequency of spontaneous G:C to T:A
      mutations, and the deficiency of MutT leads to the enhancement of T:A to G:C
      transversions more than 1000-fold over the control level. In humans, the
      functional homologues of MutM, MutY and MutT, i.e., OGG1, MUTYH (MYH) and MTH1,
      contribute to the protection of genomic DNA from oxidative stress. Interestingly,
      several polymorphic forms of these proteins exist in human populations, and some
      of them are suggested to be associated with cancer susceptibility. Here, we
      review the polymorphic forms of OGG1, MUTYH and MTH1 involved in repair of 8-OH-G
      and 8-OH-dGTP, and discuss the significance of the polymorphisms in the
      maintenance of genomic integrity. We also summarize the polymorphic forms of
      human DNA polymerase eta, which may be involved in damage tolerance and
      mutagenesis induced by oxidative stress.

PMID- 16081111
TI  - Mefloquine inhibits cholinesterases at the mouse neuromuscular junction.
AB  - Mefloquine is effective against drug-resistant Plasmodium falciparum. This
      property, along with its unique pharmacokinetic profile, makes mefloquine a
      widely prescribed antimalarial drug. However, mefloquine has neurologic effects
      which offset its therapeutic advantages. Cellular actions underlying mefloquine's
      neurologic effects are poorly understood. Here, we demonstrate that mefloquine
      inhibits human recombinant acetylcholinesterase. To explore the consequences of
      this action, we investigated mefloquine's actions at a model cholinergic synapse,
      the mouse neuromuscular junction. Sharp electrode recording was used to record
      miniature endplate potentials (mepps) in the Triangularis sterni muscle. Within
      30 min of exposure to 10 microM mefloquine, mepps were altered in three ways: 10
      90% rise time, 90-10% decay time and amplitude significantly increased. Mepp
      decay time increased linearly with mefloquine concentration. Pretreatment of
      muscles with the cholinesterase inhibitor physostigmine (3 microM) precluded the
      mefloquine-induced prolongation of mepp decay. Mefloquine also prolonged mepps at
      endplates of acetylcholinesterase knock-out mice. Since the selective
      butyrylcholinesterase inhibitor iso-OMPA (100 microM) also prolonged mepp decay
      at the neuromuscular junction of acetylcholinesterase knock-out mice, mefloquine
      inhibition of this enzyme is physiologically relevant. The non-selective anti
      cholinesterase action can contribute to the neurologic effects of mefloquine.

PMID- 16081112
TI  - Too much of a good thing: neurobiology of non-homeostatic eating and drug abuse.
AB  - In this paper, a framework involving four aspects to be considered when
      establishing an operational definition of non-homeostatic appetitive behavior is
      presented. The four aspects are (1) the quantity of the commodity consumed, (2)
      the quality or type of commodity consumed, (3) the context in which the behavior
      occurs, and (4) the specific kind of behavior that is directed toward obtaining
      and consuming the commodity of interest. This framework permits comparisons among
      a variety of non-homeostatic behaviors and accommodates different theoretical
      approaches reflected in the use of mechanistic, systems, behavioral, nutritional,
      and clinical experimental strategies. The speakers of this symposium were
      selected to emphasize the four aspects of non-homeostatic behavior, to represent
      several different approaches, and to facilitate discussion regarding neural
      similarities and differences between non-homeostatic eating and drug abuse. The
      various talks illustrated that boundaries need not exist among research fields,
      and that communication among the various areas enhances the research effort.

PMID- 16081113
TI  - Responses of calves to acute stress: individual consistency and relations between
      behavioral and physiological measures.
AB  - The present study examined the consistency over time of individual differences in
      behavioral and physiological responsiveness of calves to intuitively alarming
      test situations as well as the relationships between behavioral and physiological
      measures. Twenty Holstein Friesian heifer calves were individually subjected to
      the same series of two behavioral and two hypothalamo-pituitary-adrenocortical
      (HPA) axis reactivity tests at 3, 13 and 26 weeks of age. Novel environment (open
      field, OF) and novel object (NO) tests involved measurement of behavioral, plasma
      cortisol and heart rate responses. Plasma ACTH and/or cortisol response profiles
      were determined after administration of exogenous CRH and ACTH, respectively, in
      the HPA axis reactivity tests. Principal component analysis (PCA) was used to
      condense correlated measures within ages into principal components reflecting
      independent dimensions underlying the calves' reactivity. Cortisol responses to
      the OF and NO tests were positively associated with the latency to contact and
      negatively related to the time spent in contact with the NO. Individual
      differences in scores of a principal component summarizing this pattern of inter
      correlations, as well as differences in separate measures of adrenocortical and
      behavioral reactivity in the OF and NO tests proved highly consistent over time.
      The cardiac response to confinement in a start box prior to the OF test was
      positively associated with the cortisol responses to the OF and NO tests at 26
      weeks of age. HPA axis reactivity to ACTH or CRH was unrelated to adrenocortical
      and behavioral responses to novelty. These findings strongly suggest that the
      responsiveness of calves was mediated by stable individual characteristics.
      Correlated adrenocortical and behavioral responses to novelty may reflect
      underlying fearfulness, defining the individual's susceptibility to the
      elicitation of fear. Other independent characteristics mediating reactivity may
      include activity or coping style (related to locomotion) and underlying sociality
      (associated with vocalization).

PMID- 16081114
TI  - Illudalane sesquiterpenoids, echinolactones A and B, from a mycelial culture of
      Echinodontium japonicum.
AB  - Illudalane sesquiterpenoids, echinolactones A and B, were isolated from the
      culture broth of the fungus Echinodontium japonicum, and their structures
      spectroscopically determined.

PMID- 16081115
TI  - Volatile profiling of Arabidopsis thaliana - putative olfactory compounds in
      plant communication.
AB  - Arabidopsis thaliana from the Brassicaceae family has arisen as the model
      organism in plant biology research. The plant's genome has been characterized and
      worldwide studies are conducted at the genetic, protein and metabolic level to
      unravell the function of genes involved in growth, reproduction, biosynthesis,
      and plant communication. As part of the multidisciplinary project BIOEMIT at
      NTNU, metabolomic studies of Arabidopsis T-DNA knock-out mutants and ecotypes
      have been carried out. Volatile profiles of autolyzed, intact plants and single
      plant organs were obtained by solid-phase microextraction coupled with gas
      chromatography-mass spectrometry. The studies were aimed at the diversity of
      defense-related compounds from the glucosinolate-myrosinase system - the
      isothiocyanates and nitriles. Metabolites from methionine, leucine and
      phenylalanine-derived glucosinolates were most abundant (4-methylthiobutyl, 4
      methylpentyl, 2-phenylethyl). In addition, 24 monoterpenes, 26 sesquiterpenes and
      12 aromatic structures, predominantly observed in inflorescenses, are described.
      Excluding the vast group of straight chain aliphatic structures, a total of 102
      volatile compounds were detected, of which 59 are reported in Arabidopsis
      thaliana for the first time, thus emphasizing the sensitivity and applicability
      of solid-phase microextraction for volatile profiling of plant secondary
      metabolites.

PMID- 16081116
TI  - Isolation and absolute configuration of new bioactive marine steroids from
      Euryspongia n. sp.
AB  - The apolar fraction of the crude alcoholic extract of the sponge Euryspongia n.
      sp. was shown to display anti-inflammatory activity. Bioassay guided
      chromatographic purification led to the isolation of a known compound petrosterol
      (1) of 3beta-hydroxy-24-norchol-5-en-23-oic acid (2), which has never yet been
      found as a natural substance, and of a new steroid, 3beta-hydroxy-26-norcampest-5
      en-25-oic acid (3). The absolute configurations of 2 and 3 were deduced from
      comparative 1H NMR data of the (S)- and (R)-phenylglycine methyl ester
      derivatives. These compounds were evaluated for their anti-inflammatory activity
      against 6-keto-prostaglandinF1alpha release in a human keratinocyte cell line
      HaCaT.

PMID- 16081117
TI  - Distinct roles of NF-kappaB p50 in the regulation of acetaminophen-induced
      inflammatory mediator production and hepatotoxicity.
AB  - Oxidative stress plays an important role in acetaminophen (APAP)-induced
      hepatotoxicity. In addition to inducing direct cellular damage, oxidants can
      activate transcription factors including NF-kappaB, which regulate the production
      of inflammatory mediators implicated in hepatotoxicity. Here, we investigated the
      role of APAP-induced oxidative stress and NF-kappaB in inflammatory mediator
      production. Treatment of mice with APAP (300 mg/kg, i.p.) resulted in
      centrilobular hepatic necrosis and increased serum aminotransferase levels. This
      was correlated with depletion of hepatic glutathione and CuZn superoxide
      dismutase (SOD). APAP administration also increased expression of the
      proinflammatory mediators, interleukin-1beta (IL-1beta), tumor necrosis factor
      alpha (TNFalpha), macrophage chemotactic protein-1 (MCP-1), and KC/gro, and the
      anti-inflammatory cytokine, interleukin-10 (IL-10). Pretreatment of mice with the
      antioxidant, N-acetylcysteine (NAC) prevented APAP-induced depletion of
      glutathione and CuZnSOD, as well as hepatotoxicity. NAC also abrogated APAP
      induced increases in TNFalpha, KC/gro, and IL-10, but augmented expression of the
      anti-inflammatory cytokines interleukin-4 (IL-4) and transforming growth factor
      beta (TGFbeta). No effects were observed on IL-1beta or MCP-1 expression. To
      determine if NF-kappaB plays a role in regulating mediator production, we used
      transgenic mice with a targeted disruption of the gene for NF-kappaB p50. As
      observed with NAC pretreatment, the loss of NF-kappaB p50 was associated with
      decreased ability of APAP to upregulate TNFalpha, KC/gro, and IL-10 expression
      and increased expression of IL-4 and TGFbeta. However, in contrast to NAC
      pretreatment, the loss of p50 had no effect on APAP-induced hepatotoxicity. These
      data demonstrate that APAP-induced cytokine expression in the liver is influenced
      by oxidative stress and that this is dependent, in part, on NF-kappaB. However,
      NF-kappaB p50-dependent responses do not appear to play a major role in the
      pathogenesis of toxicity in this model.

PMID- 16081118
TI  - Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen
      species.
AB  - Developmental pathologies may result from endogenous or xenobiotic-enhanced
      formation of reactive oxygen species (ROS), which oxidatively damage cellular
      macromolecules and/or alter signal transduction. This minireview focuses upon
      several model drugs (phenytoin, thalidomide, methamphetamine), environmental
      chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in
      vivo and in embryo culture using mouse, rat and rabbit models. Embryonic
      prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics to
      free radical intermediates that initiate ROS formation, resulting in oxidation of
      proteins, lipids and DNA. Oxidative DNA damage and embryopathies are reduced in
      PHS knockout mice, and in mice treated with PHS inhibitors, antioxidative
      enzymes, antioxidants and free radical trapping agents. Thalidomide causes
      embryonic DNA oxidation in susceptible (rabbit) but not resistant (mouse)
      species. Embryopathies are increased in mutant mice deficient in the
      antioxidative enzyme glucose-6-phosphate dehydrogenase (G6PD), or by glutathione
      (GSH) depletion, or inhibition of GSH peroxidase or GSH reductase. Inducible
      nitric oxide synthase knockout mice are partially protected. Inhibition of Ras or
      NF-kB pathways reduces embryopathies, implicating ROS-mediated signal
      transduction. Atm and p53 knockout mice deficient in DNA damage response/repair
      are more susceptible to xenobiotic or radiation embryopathies, suggesting a
      teratological role for DNA damage, consistent with enhanced susceptibility to
      methamphetamine in ogg1 knockout mice with deficient repair of oxidative DNA
      damage. Even endogenous embryonic oxidative stress carries a risk, since
      untreated G6PD- or ATM-deficient mice have increased embryopathies. Thus,
      embryonic processes regulating the balance of ROS formation, oxidative DNA damage
      and repair, and ROS-mediated signal transduction may be important determinants of
      teratological risk.

PMID- 16081119
TI  - Cobra cardiotoxin-induced cell death in fetal rat cardiomyocytes and cortical
      neurons: different pathway but similar cell surface target.
AB  - Cobra cardiotoxins (CTXs) are basic polypeptides with diverse pharmacological
      functions that are cytotoxic to many different cell types through both necrotic
      and apoptotic cell death pathways. In this comparative study of the action of CTX
      A3 from the Taiwan cobra (Naja atra) on fetal rat cardiomyocytes and cortical
      neurons, it was shown that CTX A3 induced different patterns of elevation of
      intracellular Ca2+ concentration ([Ca2+]i), CTX internalization, caspase-3
      activity and viability. Application of an anti-sulfatide monoclonal antibody, O4
      specific for 3-sulfo-galactose lipid, but not in the control experiments using
      anti-GM3 monoclonal antibody, reduces CTX-induced [Ca2+]i elevation, CTX
      internalization and toxicity. Therefore, CTX may target similar sulfo-containing
      cell surface receptors in both fetal rat cardiomyocytes and cortical neurons, but
      induce cell death through different pathways specific to each cell type.

PMID- 16081120
TI  - Characterization of different viruses infecting the marine harmful algal bloom
      species Phaeocystis globosa.
AB  - Twelve lytic viruses (PgV) infecting the marine unicellular eukaryotic harmful
      algal bloom species Phaeocystis globosa were isolated from the southern North Sea
      in 2000-2001 and partially characterized. All PgV isolates shared common
      phenotypic features with other algal viruses belonging to the family
      Phycodnaviridae and could be categorized in four different groups. Two main
      groups (PgV Group I and II) were discriminated based on particle size (150 and
      100 nm respectively), genome size (466 and 177 kb) and structural protein
      composition. The lytic cycle showed a latent period of 10 h for PgV Group I and
      latent periods of 12 h and 16 h for PgV Group IIA and IIB. Host specificity and
      temperature sensitivity finally defined a fourth group (PgV Group IIC). Our
      results imply that viral infection plays an important role not only in P. globosa
      dynamics but also in the diversity of both host and virus community.

PMID- 16081121
TI  - Detection of amantadine-resistant variants among avian influenza viruses isolated
      in North America and Asia.
AB  - Here, we report the diversity of amantadine-resistant mutants among avian
      influenza A viruses with pandemic potential (H5, H6, H7, and H9 hemagglutinin
      subtypes). Drug-resistant variants were not detected among 1979--83 isolates,
      whereas 31.1% of H5 and 10.6% of H9 strains from Southeast Asia isolated in 2000
      04 carried mutations in M2 protein. In North America, resistant variants occurred
      among H7 viruses only (16.4% of those tested). H6 viruses were amantadine
      sensitive. These findings prompt concern regarding the control of pandemic
      influenza, the possibility that the next pandemic virus will be amantadine
      resistant and the need to monitor the use of the drug in poultry.

PMID- 16081122
TI  - Gene order constrains adaptation in bacteriophage T7.
AB  - The order of genes in the genome is commonly thought to have functional
      significance for gene regulation and fitness but has not heretofore been tested
      experimentally. We adapted a bacteriophage T7 variant harboring an ectopically
      positioned RNA polymerase gene to determine whether it could regain the fitness
      of the wild type. Two replicate lines maintained the starting gene order and
      showed only modest recovery of fitness, despite the accumulation of over a dozen
      mutations. In both lines, a mutation in the early terminator signal is
      responsible for the majority of the fitness recovery. In a third line, the phage
      evolved a new gene order, restoring the wild-type position of the RNA polymerase
      gene but also displacing several other genes to ectopic locations. Due to the
      recombination, the fitness of this replicate was the highest obtained but it
      falls short of the wild type adapted to the same growth conditions. The large
      benefits afforded by the terminator mutation and the recombination are explicable
      in terms of T7 biology, whereas several mutations with lesser benefits are not
      easily accounted for. These results support the premise that gene order is
      important to fitness and that wild-type fitness is not rapidly re-evolved in
      reorganized genomes.

PMID- 16081123
TI  - A bipartite Tobacco mosaic virus-defective RNA (dRNA) system to study the role of
      the N-terminal methyl transferase domain in cell-to-cell movement of dRNAs.
AB  - Plant viruses, in particular Tobacco mosaic virus (TMV), are model systems to
      study RNA and protein trafficking in plants. Although TMV cell-to-cell transport
      controlled by the 30-kDa movement protein (MP) has been intensively studied, it
      was only recently demonstrated that the 126/183-kDa replicase proteins are also
      involved in cell-to-cell movement. Elucidating the role(s) of 126/183-kDa
      proteins in movement is complicated because these proteins have multiple
      functions associated with replication and gene expression. To overcome these
      difficulties we developed a TMV helper virus-defective RNA (dRNA) system to study
      the role of replicase protein sequences in dRNA cell-to-cell movement.
      Artificially constructed dRNAs lacking sequences encoding the helicase and
      polymerase domains of the replicase proteins and portions of the MP were viable
      in protoplasts and plants in the presence of helper virus. Expression of at least
      approximately 50% of the methyl transferase (MT) domain was required for
      efficient dRNA movement in Nicotiana benthamiana. dRNAs that encoded the N
      terminal 64 replicase amino acids or lacked a translatable MT domain failed to
      move or moved poorly. TMV dRNAs expressing 258 amino acids of the replicase
      protein moved into all specialized non-vascular tissues, whereas dRNAs expressing
      replicase sequences beyond amino acid 258 were restricted to the epidermis and
      palisade mesophyll tissues. Furthermore, second-site mutations within the dRNA
      encoded truncated replicase protein altered efficiency in dRNA cell-to-cell
      movement.

PMID- 16081124
TI  - Serine-scanning mutagenesis studies of the C-terminal heptad repeats in the SARS
      coronavirus S glycoprotein highlight the important role of the short helical
      region.
AB  - The fusion subunit of the SARS-CoV S glycoprotein contains two regions of
      hydrophobic heptad-repeat amino acid sequences that have been shown in
      biophysical studies to form a six-helix bundle structure typical of the fusion
      active core found in Class I viral fusion proteins. Here, we have applied serine
      scanning mutagenesis to the C-terminal-most heptad-repeat region in the SARS-CoV
      S glycoprotein to investigate the functional role of this region in membrane
      fusion. We show that hydrophobic sidechains at a and d positions only within the
      short helical segment of the C-terminal heptad-repeat region (I1161, I1165,
      L1168, A1172, and L1175) are critical for cell-cell fusion. Serine mutations at
      outlying heptad-repeat residues that form an extended chain in the core structure
      (V1158, L1179, and L1182) do not affect fusogenicity. Our study provides genetic
      evidence for the important role of alpha-helical packing in promoting S
      glycoprotein-mediated membrane fusion.

PMID- 16081125
TI  - Accuracy of identification of grating contrast by human observers: Bayesian
      models of V1 contrast processing show correspondence between discrimination and
      identification performance.
AB  - This paper presents the results of a contrast identification study, where
      accuracy in identification is quantified as mutual information between stimulus
      contrast and observer's response. The stimulus was a set of 2-8 gratings,
      spanning the range of visible contrasts. Gratings from the set were presented
      individually for 500 ms, and the observer had to respond by giving the number
      label corresponding to the contrast of the grating presented. Mutual information
      increased with set size up to a maximum of around 2.35 bits, i.e., only 5 clearly
      identifiable contrasts. Set sizes greater than 5 showed a plateau or decline in
      performance. These data were well fit by Bayesian models of V1 contrast coding,
      with the parameters obtained by fitting the contrast discrimination results of
      Chirimuuta and Tolhurst [Chirimuuta, M., & Tolhurst, D. J. (2005). Does a
      Bayesian model of V1 contrast coding offer a neurophysiological account of human
      contrast discrimination? Vision Research].

PMID- 16081126
TI  - Achromatic contrast effects in infants: adults and 4-month-old infants show
      similar deviations from Wallach's ratio rule.
AB  - When adults view a disk of light embedded in a higher luminance surround, the
      perceived lightness of the disk is largely determined by the surround to disk
      luminance ratio (Wallach's ratio rule). In the present study, both adult and
      infant subjects were tested with multiple discrete trial procedures in which the
      surround luminance was decreased between the study and test phases of each trial.
      Tested with sequential lightness matching, adult subjects showed an approximate
      ratio rule, with a small but consistent deviation in the direction of a luminance
      match. Tested with a forced-choice novelty preference technique in combination
      with a cross-familiarization paradigm, 4-month-old infants showed preference
      minima that fell closer to the mean adult match than to the ratio rule. This
      finding suggests that, at least for a relatively simple visual display, 4-month
      old infants' looking preferences are governed by an adult-like achromatic
      contrast system.

PMID- 16081127
TI  - Scotopic threshold responses to infrared irradiation in cats.
AB  - Infrared (IR) irradiation is frequently used in ophthalmological diagnosis and
      treatment. It has been used to selectively stimulate photodiode-based retinal
      prostheses to prove their function. Data concerning the natural IR-sensitivity of
      the retina are contradictory. In our experiments in dark-adapted cats an IR-laser
      (826 nm) and IR emitting diodes (875 nm) elicited clear scotopic threshold
      responses. Comparison of the two lasers (IR and a visible laser at 670 nm) using
      Lambs template and our experimental data revealed very similar differences in
      retinal sensitivity (4.28 and 3.94+/-0.29 log units, respectively). The fact that
      the cat retina is sensitive to IR-irradiation under certain conditions has
      important implications in interpreting the results from retinal prostheses and
      rewards further attention in its use in many ophthalmological applications.

PMID- 16081128
TI  - Does a Bayesian model of V1 contrast coding offer a neurophysiological account of
      human contrast discrimination?
AB  - The dipper effect for contrast discrimination provides strong evidence that the
      underlying neural response is accelerating at low contrasts and saturating at
      high contrasts. The contrast-response functions of V1 neurons do have this
      sigmoidal shape, but individual neurons do not generally have a dynamic range
      wide enough to account for the dipper effect. This paper presents a Bayesian
      model of neurons in monkey V1, whose contrast-response function is described by a
      modified Naka-Rushton with multiplicative noise. It is shown that a model of
      groups of twelve or more neurons gives a reasonable explanation of the
      psychophysical data of two observers, but there is a large systematic error which
      is apparently due to the shape of the distribution of the monkey's sensitivity
      parameter, c50. A further model provides a better fit to the data by sacrificing
      strict adherence to V1 neuronal parameters and, instead using an arbitrary
      bimodal c50 distribution, perhaps reflecting differences between M- and P-cells.

PMID- 16081129
TI  - Nucleic acid fluorochromes and flow cytometry prove useful in assessing the
      effect of chlorination on drinking water bacteria.
AB  - Flow cytometry (FCM), combined with staining using two fluorochromes (propidium
      iodide, PI, or SYBR Green II RNA gel stain, SYBR-II), was used to assess nucleic
      acid injuries to chlorinated drinking water bacteria. Highly fluorescent SYBR-II
      stained bacteria were converted to bacteria with low fluorescence after
      chlorination. PI staining of bacteria exposed to different doses of chlorine
      showed membrane permeabilisation ([Cl2] < 0.2 mg L(-1)) and nucleic acid damage
      at higher doses ([Cl2] > 0.3 mg L(-1)). Above a threshold dose (between 1.5 and 3
      mg Cl2 L(-1)), nucleic acids appeared severely damaged and incapable of being
      stained by PI or SYBR-II. These results constitute evidence that FCM is a
      promising tool for assessing drinking water bacteria injuries and for controlling
      chlorine disinfection efficiency much more rapidly than the standard sensitive
      but time-consuming heterotrophic plate count method.

PMID- 16081130
TI  - Inactivation of particle-associated viral surrogates by ultraviolet light.
AB  - This study investigated whether colloid-sized particles can enmesh and protect
      viruses from 254-nm ultraviolet (UV) light and sought to determine the particle
      characteristics (e.g. size, chemical composition) that are most relevant in
      causing a protective effect. Two viral surrogates (MS2 coliphage and
      bacteriophage T4), three types of particles (kaolin clay, humic acid powder, and
      activated sludge), two coagulants (alum and ferric chloride), two filtration
      conditions (none and 0.45 microm), and two UV doses (40 and 80 mJ/cm2 for MS2
      coliphage; 2 and 7 mJ/cm2 for bacteriophage T4) were considered in a series of
      bench-scale UV collimated beam experiments. Transmission electron microscopy was
      used to qualitatively confirm the phage particle-association after coagulation.
      Humic acid and activated sludge floc particles shielded both viral surrogates to
      a statistically significant degree (with >99% confidence) relative to particle
      free control conditions, while the kaolin clay particles provided no significant
      protection. The results of the study suggest that particles <2 microm in diameter
      are large enough to protect viruses from UV light and that particulate chemical
      composition (e.g. UV-absorbing organic content) may be a critical factor in the
      survival of particle-associated viruses during UV disinfection.

PMID- 16081131
TI  - Accumulation of chromium (VI) from aqueous solutions using water lilies (Nymphaea
      spontanea).
AB  - This study describes an investigation using tropical water lilies (Nymphaea
      spontanea) to remove hexavalent chromium from aqueous solutions and
      electroplating waste. The results show that water lilies are capable of
      accumulating substantial amount of Cr(VI), up to 2.119 mg g(-1) from a 10 mg l(
      1) solution. The roots of the plant accumulated the highest amount of Cr(VI)
      followed by leaves and petioles, indicating that roots play an important role in
      the bioremediation process. The maturity of the plant exerts a great effect on
      the removal and accumulation of Cr(VI). Plants of 9 weeks old accumulated the
      most Cr(VI) followed by those of 6 and 3 weeks old. The results also show that
      removal of Cr(VI) by water lilies is more efficient when the metal is present
      singly than in the presence of Cu(II) or in waste solution. This may be largely
      associated with more pronounced phytotoxicity effect on the biochemical changes
      in the plants and saturation of binding sites. Significant toxicity effect on the
      plant was evident as shown in the reduction of chlorophyll, protein and sugar
      contents in plants exposed to Cr(VI) in this investigation.

PMID- 16081132
TI  - Effects of medium-pressure UV lamps radiation on water quality in a chlorinated
      indoor swimming pool.
AB  - The aim of our study was to determine the impact of medium-pressure UV lamps
      radiation on water quality in a chlorinated indoor swimming pool. An indoor
      swimming pool was equipped with two medium-pressure UV lamps. We collected eight
      samples of water daily over a four-weeks period and measured total and free
      chlorine, pH, water temperature, bacteriological parameters, total organic carbon
      and trihalomethanes. During the first week, which served as control, medium
      pressure UV lamps were turned off. During the next three weeks, medium-pressure
      UV lamps were kept on 24 h per day. The third week, we reduced the level of the
      injected chlorine into water, and the last week we also reduced the water renewal
      volume by 27%. Our results showed that bacteriological parameters remained within
      allowable french limits. When medium-pressure UV lamps were kept on, total, free
      and active chlorine levels were significantly increased (P<0.001), whereas
      combined chlorine level were significantly decreased (P<0.001 and P<0.05,
      respectively). The levels of chloroform and bromodichloromethane were
      significantly increased when medium-pressure UV lamps were kept on (P<0.001),
      whereas chlorodibromomethane and bromoform levels significantly decreased (P<0.05
      and P<0.001, respectively). The additional formation of chloroform and
      bromodichloromethane may be explained by the increase in active chlorine and by
      radicalizing mechanisms initiated by UV radiation.

PMID- 16081133
TI  - The performance of an anaerobic sequencing batch biofilm reactor treating
      domestic sewage colonized by anoxygenic phototrophic bacteria.
AB  - There are few reports on morphological characterization of microbial population
      colonizing anaerobic bioreactors and the aim of this work was to access such
      variable in an anaerobic sequencing batch biofilm reactor treating the University
      of Sao Paulo (Sao Carlos city, Brazil) domestic sewage. This pilot-scale reactor
      (1.2m3) has been treating 0.65 m3 of liquid waste under cycles of 8h. The ASBBR
      has the distinct characteristics of being filled with support material for
      biomass attachment with the aim of skipping the sedimentation phase during the
      operational cycles, as it is commonly observed in anaerobic sequencing batch
      reactors (ASBR). Physical, chemical and physico-chemical variables were accessed
      in the influent and in the effluent for performance evaluation. Microbial
      characterization was made by means of direct microscopy and samples were taken
      over 150 d with a 25 d period interval. The ASBBR attained approximately 60% of
      COD removal efficiency. Microscopic analysis of biomass showed the presence of
      anoxygenic phototrophic bacteria probably influencing the ASBBR performance in
      the domestic sewage treatment. It is very likely that the exclusion of
      phototrophic sulfur bacteria by efficiently restraining the light would enhance
      the bioreactor efficiency.

PMID- 16081134
TI  - Heavy metal ion influence on the photosynthetic growth of Rhodobacter
      sphaeroides.
AB  - The potential of purple non-sulphur bacteria for bioremediation was assessed by
      investigating the ability of Rhodobacter sphaeroides strain R26.1 to grow
      photosynthetically in heavy metal contaminated environments. Bacterial cultures
      were carried out in artificially polluted media, enriched with the transition
      metal ions Hg2+, Cu2+, Fe2+, Ni2+, Co2+, MoO4(2-), and CrO4(2-) in millimolar
      concentration range. For each investigated ion the effect on growth parameters
      was evaluated. The analysis of concentration-effect curves revealed a
      differentiated response, indicating that diverse mechanisms of tolerance and/or
      resistance are involved. Adaptation or selection procedures were not applied,
      leading to assess intrinsic abilities of coping with these contaminants. The
      microorganism proved to be highly tolerant to heavy metal exposure, especially
      towards Co2+, Fe2+ and MoO4(2-). In addition Ni2+ and Co2+ were found to decrease
      the cellular content of light harvesting complexes. A characteristic behavior was
      observed with mercuric ions, which produced a significant increase of the lag
      phase.

PMID- 16081135
TI  - Humic-like substances extracted from composts can promote the photodegradation of
      Irgarol 1051 in solar light.
AB  - Humic-like substances (HLS) were extracted from a mixture of sewage sludges and
      trimmings (70-30%, w/w) after different times of composting (0, 70 days and 130
      days). HLS were analyzed by elemental analysis, UV-visible and fluorescence
      spectroscopy and also tested for their ability to photosensitize the degradation
      of Irgarol. The rate of Irgarol photodegradation in artificial solar light was
      found to be 2.5- to 4.3-fold higher in the presence of HLS than in buffered Milli
      Q water. These results were confirmed by experiments in solar light that
      evidenced the photodegrading properties of HLS in a more striking way. Using 2
      propanol as hydroxyl radical scavenger, we could show that hydroxyl radicals
      contributed to the photosensitized Irgarol degradation for about 25%. The
      photodegrading activity of HLS, their absorbance and their emissive properties
      were all found to increase between 0 and 70 days of composting and to remain
      quite constant between 70 and 130 days. The degree of humification varied in the
      same way, linking all these properties to the humification process.

PMID- 16081136
TI  - Toxicity of copper on rice growth and accumulation of copper in rice grain in
      copper contaminated soil.
AB  - Pot soil experiments showed that copper (Cu) is highly toxic to rice. Rice grain
      yields decreased exponentially and significantly with the increase of soil Cu
      levels. Rice grain yield was reduced about 10% by soil Cu level of 100 mg kg(-1),
      about 50% by soil Cu level of 300-500 mg kg(-1) and about 90% by soil Cu
      concentration of 1,000 mg kg(-1). Root was more sensitive to soil Cu toxicity
      than other parts of rice plant at relatively lower soil Cu levels (less than 300
      500 mg kg(-1)), but the growth of whole rice plant was severely inhibited at high
      soil Cu levels (300-500 mg kg(-1) or above). Cu concentrations in rice grain
      increased with soil Cu levels below 150-200 mg kg(-1), but decreased with soil Cu
      levels above 150-200 mg kg(-1), with peak Cu concentration at soil Cu level of
      150-20 mg kg(-1). Cu was not distributed evenly in different parts of rice grain.
      Cu concentration in cortex (embryo) was more than 2-fold that in chaff and
      polished rice. More than 60% of the Cu in grain was accumulated in polished rice,
      about 24% in cortex (embryo), and about 12% in chaff. So, about 1/3 of the Cu in
      rice grain was eliminated after grain processing (chaff, cortex and embryo was
      removed).

PMID- 16081137
TI  - Enantiomeric separation of metolachlor and its metabolites using LC-MS and CZE.
AB  - The stereoisomers of metolachlor and its two polar metabolites [ethane sulfonic
      acid (ESA) and oxanilic acid (OXA)] were separated using liquid chromatography
      mass spectrometry (LC-MS) and capillary zone electrophoresis (CZE), respectively.
      The separation of metolachlor enantiomers was achieved using a LC-MS equipped
      with a chiral stationary phase based on cellulose tris(3,5-dimethylphenyl
      carbamate) and an atmospheric pressure chemical ionization source operated under
      positive ion mode. The enantiomers of ESA and OXA were separated using CZE with
      gamma-cyclodextrin (gamma-CD) as chiral selector. Various CZE conditions were
      investigated to achieve the best resolution of the ESA and OXA enantiomers. The
      optimum background CZE electrolyte was found to consist of borate buffer (pH=9)
      containing 20% methanol (v/v) and 2.5% gamma-CD (w/v). Maximum resolution of ESA
      and OXA enantiomers was achieved using a capillary temperature of 15 degrees C
      and applied voltage of 30 kV. The applicability of the LC-MS and CZE methods was
      demonstrated successfully on the enantiomeric analysis of metolachlor and its
      metabolites in samples from a soil and water degradation study that was set up to
      probe the stereoselectivity of metolachlor biodegradation. These techniques allow
      the enantiomeric ratios of the target analytes to be followed over time during
      the degradation process and thus will prove useful in determining the role of
      chirality in pesticide degradation and metabolite formation.

PMID- 16081138
TI  - Scaling characteristics in ozone concentration time series (OCTS).
AB  - One-year series of hourly average ozone observations, which were obtained from
      urban and national park air monitoring stations at Taipei (Taiwan), were analyzed
      by means of descriptive statistics and fractal methods to examine the scaling
      structures of ozone concentrations. It was found that all ozone measurements
      exhibited the characteristic right-skewed frequency distribution, cyclic pattern,
      and long-term memory. A mono-fractal analysis was performed by transferring the
      ozone concentration time series (OCTS) into a useful compact form, namely, the
      box-dimension (D(B))-threshold (T(h)) and critical scale (C(S))-threshold (T(h))
      plots. Scale invariance was found in these time series and the box dimension was
      shown to be a decreasing function of the threshold ozone level, implying the
      existence of multifractal characteristics. To test this hypothesis, the OCTS were
      transferred into the multifractal spectra, namely, the tau(q)-q plots. The
      analysis confirmed the existence of multifractal characteristics in the
      investigated OCTS. A simple two-scale Cantor set with unequal scales and weights
      was then used to fit the calculated tau(q)-q plots. This model fitted remarkably
      well the entire spectrum of scaling exponents for the examined OCTS. Because the
      existence of chaos behavior in OCTS has been reported in the literature, the
      possibility of a chaotic multifractal approach for OCTS characterization was
      discussed.

PMID- 16081139
TI  - Arsenate (As) uptake by and distribution in two cultivars of winter wheat
      (Triticum aestivum L.).
AB  - Two cultivars of winter wheat (Triticum aestivum L.) (Jing 411 and Lovrin 10)
      were used to investigate arsenate (As) uptake and distribution in plants grown in
      hydroponic culture and in the soil. Results showed that without As addition,
      Lovrin 10 had higher biomass than Jing 411 in the soil pot experiment; in the
      hydroponic experiment Lovrin 10 had similar root biomass to and lower shoot
      biomass than Jing 411. Increasing P supply from 32 to 161 microM resulted in
      lower tissue As concentrations, and increasing As supply from 0 to 2,000 microM
      resulted in lower tissue P concentrations. Increasing P supply tended to increase
      shoot-to-root ratios of As concentrations, and increasing As supply tended to
      decrease shoot-to-root ratios of As concentrations. Both cultivars invested more
      in root production under P deficient conditions than under P sufficient
      conditions. Lovrin 10 invested more biomass production to roots than Jing 411,
      which might be partly responsible for higher shoot P and As concentrations and
      higher shoot-to-root ratios of As concentrations. Moreover, Lovrin 10 allocated
      less As to roots than Jing 411 and the difference disappeared with decreasing P
      supply.

PMID- 16081140
TI  - Electrolytic transformation of ordinance related compounds (ORCs) in groundwater:
      laboratory mass balance studies.
AB  - Electrolytic reactive barriers (e(-) barriers) consist of closely spaced
      permeable electrodes installed across a groundwater contaminant plume in a
      permeable reactive barrier format. Application of sufficient potential to the
      electrodes results in sequential oxidation and reduction of the target
      contaminant. The objective of this study was to quantify the mass distribution of
      compounds produced during sequential electrolytic oxidation and reduction of
      ordinance related compounds (ORCs) in a laboratory analog to an e(-) barrier. In
      this study, a series of column tests were conducted using RDX (hexahydro-1,3,5
      trinitro-1,3,5-triazine) and TNT (2,4,6-trinitrotoluene) as representative ORCs.
      The experimental setup consisted of a plexiglass column packed with quartz
      feldspar sand to simulate aquifer conditions. A single set of porous electrodes
      consisting of expanded titanium-mixed metal oxide mesh was placed at the midpoint
      of the sand column as a one-dimensional analog to an e(-) barrier. Constant
      current of 20mA (variable voltage) was applied to the electrode set. Initial
      studies involved quantification of reaction products using unlabeled RDX and TNT.
      Approximately 70% of the influent concentration was transformed, in one pass,
      through sequential oxidation-reduction for both contaminants. Following the
      unlabeled studies, (14)C labeled RDX and TNT were introduced to determine the
      mass balance. An activity balance of up to 96% was achieved for both (14)C-RDX
      and (14)C-TNT. For both contaminants, approximately 21% of the influent activity
      was mineralized to (14)CO(2). The proportion of the initial activity in the
      dissolved fraction was different for the two test contaminants. Approximately 30%
      of the initial (14)C-RDX was recovered as unreacted in the dissolved phase. The
      balance of the (14)C-RDX was recovered as non-volatile, non-nitroso
      transformation products. None of the (14)C-RDX was sorbed to the column sand
      packing. For (14)C-TNT approximately 51% of the initial activity was recovered in
      the dissolved phase, the majority was unreacted TNT. The balance of the (14)C-TNT
      was either sorbed to the sand packing (approximately 24%) or
      dissolved/mineralized as unidentified ring cleavage products ( approximately 4%).

PMID- 16081141
TI  - Fate of synthetic musks in a domestic wastewater treatment plant and in an
      agricultural field amended with biosolids.
AB  - Synthetic musks are widely used as fragrance ingredients in personal care
      products, and they enter domestic wastewater treatment plants (WWTPs) through
      discharges into municipal sewage systems. Samples of aqueous sewage and biosolids
      collected from the Peterborough Wastewater Treatment Plant (WWTP), Ontario,
      Canada were analyzed for 11 synthetic musk compounds using GC/MS. The results
      showed that 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta[g]-2
      benzopyrane (HHCB, 173.1+/-43.4 ng/L) and 7-acetyl-1,1,3,4,4,6-hexamethyl
      tetrahydronaphthalene (AHTN, 41.6+/-15.8 ng/L) were the dominant fragrances in
      sewage, but other polycyclic musks and nitro musks were present at lower
      concentrations. The concentrations of HHCB and AHTN in the aqueous phase of the
      sewage were highly correlated with both BOD5 and TOC. The overall removal
      efficiency of synthetic musks from the aqueous sewage in the WWTP ranged from
      43.3% to 56.9%, but removal occurred mainly by partitioning into the biosolids.
      Based on a mass balance model, the daily input and output of HHCB and AHTN in the
      Peterborough WWTP were 47 g and 46 g, respectively. In an agricultural field
      amended with biosolids from the Peterborough WWTP, HHCB and AHTN were detected in
      soil immediately after application at mean concentrations of 1.0 and 1.3 mug/kg,
      respectively, but concentrations declined relatively rapidly over the next 6
      weeks, post-application.

PMID- 16081142
TI  - Rapid screening of DOM's metal-binding ability using a fluorescence-based
      microplate assay.
AB  - This note describes the development of a method to rapidly quantify the metal
      binding ability of low-volume DOM samples based on their fluorescence properties.
      The method uses 96-well microplates to screen the fluorescence quenching observed
      when increasing concentrations of various metals are added to the pH-buffered DOM
      sample. Only 1.6 mL of DOM sample is required to quantify the binding affinity
      for each metal and the result is obtained in a few minutes. This study presents
      results for a surface soil DOM sample for which binding was assessed for Cu2+,
      Fe2+, Ni2+ at pH 5 and 9.

PMID- 16081143
TI  - Development and application of bioaccumulation models to assess persistent
      organic pollutant temporal trends in arctic ringed seal (Phoca hispida)
      populations.
AB  - Individual- and population-based models were developed to simulate the
      bioaccumulation of persistent organic pollutants (POPs) over the lifetime of
      ringed seals (Phoca hispida) and account for the effects of age, growth, body
      condition and sex (including gestation, birth and lactation). Lactational
      transfer was described using a milk to blubber partition coefficient, which was
      shown to be a function of Kow (KMB=1/(1.676+1.293.10(-7).Kow) r2=0.60, n=32,
      p<0.001). Simulations showed that nursing mothers could transfer between 5% and
      40% of their burden of low and high KMB contaminants, respectively, to their milk
      over 40 days of lactation. The models were calibrated using a POPs dataset for 50
      seals (29 males, 21 females) from Arviat, Nunavut. They were initially calibrated
      for a group of eight highly recalcitrant PCB congeners (e.g. PCBs 153, 180)
      assuming a baseline elimination rate (ke) of about 0.03 year-1. For congeners
      more prone to biotransformation a satisfactory fit could only be reached by
      iteratively increasing ke to values ranging from 0.05 to 2.5 year-1 for PCBs 187
      and 18, respectively; thus the models became a means for estimating ke. Estimated
      ke values were correlated with a calculated index of susceptibility to
      biotransformation (ke=0.0284/Rrelr2=0.98, n=20, p<0.001). This relationship was
      used to estimate ke values used in simulations to hind-cast temporal trends of
      SigmaPCB, SigmaDDT, SigmaCHL, alphaHCH, betaHCH in ringed seal populations and to
      predict potential future trends. Results of these simulations showed good
      agreement with measured concentrations in seals from two locations in the
      Canadian Arctic (Holman Island, NWT and Arctic Bay, Nunavut) collected between
      1972 and 2001. The models show that the combined effects of rapid juvenile
      growth, a fast rate of population turnover and substantial capacity to eliminate
      many POPs result in fairly rapid responses to changes in contaminant loading,
      thus making ringed seals an effective choice for monitoring spatial and temporal
      trends of POPs in the Arctic marine ecosystem.

PMID- 16081144
TI  - Accuracy of coding for possible warfarin complications in hospital discharge
      abstracts.
AB  - BACKGROUND: Hospital discharge abstracts could be used to identify complications
      of warfarin if coding for bleeding and thromboembolic events are accurate.
      OBJECTIVES: To measure the accuracy of International Classification of Diseases,
      Ninth Revision, Clinical Modification (ICD-9CM) codes for bleeding and
      thromboembolic diagnoses. SETTING: University affiliated, tertiary care hospital
      in Ottawa, Canada. PATIENTS: A random sample of patients discharged between
      September 1999 and September 2000 with an ICD-9-CM code indicating a bleeding or
      thromboembolic diagnosis. METHODS: Gold-standard coding was determined by a
      trained chart abstractor using explicit standard diagnostic criteria for
      bleeding, major bleeding, and acute thromboembolism. The abstractor was blinded
      to the original coding. We calculated the sensitivity, specificity, positive, and
      negative predictive values of the original ICD-9CM codes for bleeding or
      thromboembolism diagnoses. RESULTS: We reviewed 616 medical records. 361 patients
      (59%) had a code indicating a bleeding diagnosis, 291 patients (47%) had a code
      indicating a thromboembolic diagnosis and 36 patients (6%) had a code indicating
      both. According to the gold standard criteria, 352 patients experienced bleeding,
      333 experienced major bleeding, and 188 experienced an acute thromboembolism. For
      bleeding, the ICD-9CM codes had the following sensitivity, specificity, positive
      and negative predictive values [95% CI]: 93% [90-96], 88% [83-91], 91% [88-94],
      and 91% [87-94], respectively. For major bleeding, the ICD-9CM codes had the
      following sensitivity, specificity, positive and negative predictive values: 94%
      [91-96], 83% [78-87], 87% [83-90], and 92% [88-95], respectively. For
      thromboembolism, the ICD-9CM codes had the following sensitivity, specificity,
      positive and negative predictive values: 97% [94-99], 74% [70-79], 62% [57-68],
      and 98% [96-99], respectively. By selecting a sub-group of ICD-9CM codes for
      thromboembolism, the positive predictive value increased to 87%. CONCLUSION: In
      our centre, the discharge abstract could be used to identify and exclude patients
      hospitalized with a major bleed or thromboembolism. If coding quality for
      bleeding is similar in other hospitals, these ICD-9-CM diagnostic codes could be
      used to study population-based warfarin-associated hemorrhagic complications
      using administrative databases.

PMID- 16081145
TI  - Changes in fibrinolysis following exercise above and below lactate threshold.
AB  - This study sought to compare fibrinolytic responses to exercise above lactate
      threshold (LT) to longer-duration, equicaloric exercise below LT. Fifteen males
      performed cycle ergometer tests above (77% VO(2)peak) and below LT (41%
      VO(2)peak) to comparatively evaluate tissue plasminogen activator (tPA) and
      plasminogen activator inhibitor-1 (PAI-1) responses. tPA activity significantly
      (P < 0.05) increased during the >LT test (pre-exercise = 1.57 +/- 0.44 IU ml(-1),
      post-exercise = 3.85 +/- 4.72 IU ml(-1)), but not the <LT test (pre-exercise =
      1.51 +/- 0.36 IU ml(-1), post-exercise = 1.94 +/- 1.00 IU ml(-1)). Plasma tPA
      antigen significantly (P < 0.05) increased during both the >LT (pre-exercise =
      8.32 +/- 4.48 ng ml(-1), post-exercise = 14.23 +/- 5.40 ng ml(-1)) and <LT (pre
      exercise = 7.40 +/- 3.52 ng ml(-1), post-exercise = 9.03 +/- 3.25 ng ml(-1))
      tests. Furthermore, post-exercise tPA antigen was greater (P < 0.05) following
      the >LT test. PAI-1 activity significantly (P < 0.05) decreased during both the
      >LT (pre-exercise = 15.00 +/- 2.73 AU ml(-1), post-exercise = 10.12 +/- 2.90 AU
      ml(-1)) and <LT (pre-exercise = 14.51 +/- 2.80 AU ml(-1), post-exercise=12.59 +/-
      2.20 AU ml(-1)) tests, and the post-exercise PAI-1 activity was significantly (P
      < 0.05) lower during the >LT test. Our results suggest that exercise <LT can
      cause fibrinolytic responses and that exercise above LT elicits greater
      fibrinolytic responses than equicaloric exercise performed below LT.

PMID- 16081146
TI  - Beyond style guides: suggestions for better scientific English.
AB  - The benefit of publishing research in English is obvious, but so is the problem:
      authors with a limited knowledge of English find it difficult to compete with
      their proficient colleagues. In this note, we offer suggestions for improving the
      English of papers in the biological sciences. The suggestions aim to help authors
      enhance writing skills, are based on our experiences as language correctors and
      do not appear in major guides to scientific writing. We also argue for the need
      for regular publication of language tips in the pages of science journals.

PMID- 16081147
TI  - A systematic review of the accuracy of diagnostic tests for inguinal lymph node
      status in vulvar cancer.
AB  - OBJECTIVE: To determine the accuracy of minimally and non-invasive tests to
      assess the groin node status in squamous cell vulvar cancer. METHODS: A
      systematic review of published research from 1979 to 2004 that compares the
      results of tests to determine groin node status with histology at inguinofemoral
      lymphadenectomy was made. Studies included in the review were those that compared
      the index test to the standard surgical intervention of inguinofemoral
      lymphadenectomy and allowed the construction of two-by-two tables. From these
      tables, sensitivity, specificity, and the likelihood ratios (with 95% confidence
      intervals) were reported and, where feasible, meta-analysis was used to pool
      results for each test separately. Sentinel node biopsy using technetium-99m
      labelled nanocolloid ((99m)Tc) had a pooled sensitivity and negative LR of 97%
      (91-100 95% CI) and 0.12 (0.053-0.28 95% CI), respectively, and was the most
      accurate test reviewed. CONCLUSION: Five diagnostic tests were identified in a
      total of 29 studies (961 groins). Although the studies were small and the design
      often poor, this represents the best summary of the data to date. Sentinel node
      identification using (99m)Tc appeared to be the most promising test for
      accurately excluding lymph node metastases in squamous cell vulvar cancer and
      potentially reducing the radicality of surgery. Its efficacy as a tool in
      reducing the need for radical surgery and associated patient morbidity without
      reducing survival needs further assessment probably in a randomised control
      trial.

PMID- 16081148
TI  - Gynecologic oncology 2005: What it "oughta" be! Presented to Society of
      Gynecologic Oncologists, Miami Beach, Florida, USA, by James W. Orr, Jr., M.D.

PMID- 16081150
TI  - The role of interstitial brachytherapy using template in locally advanced
      gynecological malignancies.
AB  - OBJECTIVE: Brachytherapy plays a major role in the treatment of patients with
      carcinoma of the cervix. However, routine intracavitary brachytherapy may not be
      feasible or adequate to treat locally advanced disease. The purpose of this
      prospective study was to assess treatment outcome for patients with locally
      advanced gynecological malignancies treated with interstitial brachytherapy using
      Martinez Universal Perineal Interstitial Template (MUPIT) and to study the acute
      and late sequelae after treatment by this technique. METHODS: Thirty previously
      untreated patients with histologically confirmed carcinoma of the cervix (20
      patients), vault (7 patients), and vagina (3 patients) were treated by a
      combination of external beam radiotherapy using megavoltage irradiation to the
      pelvis to a dose of 4000 to 5000 cGy followed by interstitial brachytherapy using
      MUPIT between June 2000 to August 2001 at Gujarat Cancer and Research Institute,
      Ahmedabad. Only those patients who were found unsuitable for conventional
      brachytherapy or in whom intracavitary radiotherapy was found to be unlikely to
      encompass the tumor volume were treated with interstitial template brachytherapy
      using MUPIT applicator and were enrolled for this study. Criteria for inclusion
      in this study were as follows: Hemoglobin--minimum 10 gm%; Performance Status-
      70% or more (Karnofsky Scale); Histopathological confirmation; FIGO Stage--IIb
      IIIb (excluding frozen pelvis). RESULTS: Among the 30 patients studied, 4 lost to
      follow-up and they were excluded from the study. With a median follow up of 9
      months, local control was achieved in (20/26) 76.92% patients. The local control
      was better for nonbulky tumors compared to bulky tumors irrespective of stage of
      disease. Local control rate was better in patients with good regression of
      disease after EBRT. The time gap between EBRT and implant also had an impact on
      the outcome. CONCLUSION: Interstitial template brachytherapy by MUPIT is a good
      alternative to deliver high-dose radiation in locally advanced gynecological
      malignancies where conventional brachytherapy application is either not feasible
      or unlikely to encompass tumor volume adequately. The locoregional control
      obtained is definitely better than external beam therapy alone and within the
      accepted range of complications. However, long-term follow-up is needed to
      comment on late morbidities.

PMID- 16081151
TI  - Primary angiosarcoma of the ovary: a case report of Stage I disease.
AB  - BACKGROUND: There are 20 documented cases of primary ovarian angiosarcoma. Most
      patients present with metastatic disease and respond poorly to chemotherapy.
      There is little information available to counsel early-staged patients on the
      need for or efficacy of adjuvant chemotherapy. CASE: We present a case of Stage
      Ic primary ovarian angiosarcoma treated with 3 cycles of adjuvant MAID
      chemotherapy. The patient is without evidence of disease 10 months post
      operatively. CONCLUSION: A review of the literature indicates a potential role
      for MAID chemotherapy in the treatment of ovarian angiosarcomas. Detection of
      Stage I disease appears to confer a better prognosis regardless of the
      utilization of adjuvant chemotherapy.

PMID- 16081152
TI  - Influence of lifestyle, health, and work environment on smoking cessation among
      Danish nurses followed over 6 years.
AB  - BACKGROUND: The purpose of this study was to examine the influence of lifestyle,
      health, and work environment on smoking cessation among Danish nurses age 45-66
      years over a 6-year period from 1993-1999. METHODS: Data derive from the Danish
      Nurse Cohort Study; a prospective cohort established in 1993 when all Danish
      female nurses 45+ years old and members of the Danish Nurses Association were
      mailed a questionnaire. The cohort was followed up 6 years later in 1999. In
      total, 12,980 responded to questions concerning smoking status in both the 1993
      and 1999 surveys. This study deals with the 4713 women (36%) who reported smoking
      at baseline. Smoking cessation was based on self-report. RESULTS: At follow-up in
      1999, 24% reported that they no longer smoked. Low prior tobacco consumption at
      baseline, high fresh fruit consumption, high blood pressure, working day shifts,
      having low physical job strain, perceiving influence on one's own work, and
      partner's socio-economic status (as measured by most recent occupation) were
      associated with successful smoking cessation. CONCLUSION: The findings from this
      study highlight the importance of various factors, including lifestyle, health
      status, and aspects of one's work environment, on successful efforts at smoking
      cessation.

PMID- 16081153
TI  - Spermatogenesis in the turkey (Meleagris gallopavo): quantitative approach in
      immature and adult males subjected to various photoperiods.
AB  - The objectives of this study were to identify and quantitate the germ cell
      populations of the testes in sexually mature male turkeys (Trial 1), determine
      the duration of meiosis based on BrdU labeling and stereological analyses (Trial
      2), and examine the impact of various photoperiods on germinal and somatic cell
      populations in immature and adult males (Trial 3). In Trial 1, both testes within
      a male had similar stereological components (P>0.05) for all parameters analyzed.
      In Trial 2, the duration of Type-1 spermatocytes and round spermatids in turkeys
      lasted 4.5+/-0.5 and 2.0+/-0.5 days, respectively. In Trial 3, the short
      photoperiod (7L:17D) delayed testicular growth (in the stereological parameters
      analyzed). In contrast, the effect of a moderately short photoperiod
      (10.5L:13.5D) was comparable to the effect of a long (14L:10D) or increasing
      photoperiod (7L:17D to 14L:10D) on the stereological parameters examined. With
      the exception of the short photoperiod, all other photoperiods used in this study
      induced comparable early testicular maturation, with maximum testis weight at 29
      35 weeks of age. As the males got older, there was a progressive, linear decline
      in testis weight through 60 weeks, at which time there were no significant
      differences among photoperiods. In conclusion, the duration of meiosis in the
      turkey was similar to that observed in the fowl and guinea-fowl. The existence of
      a threshold of photosensitivity to gonad stimulation in male turkeys is suggested
      to be between 7.0 and 10.5 h of light.

PMID- 16081154
TI  - Influence of interface surface conditions on indentation failure of simulated
      bonded ceramic onlays.
AB  - OBJECTIVE: This study aims to evaluate the influence of surface roughness and
      acid etching on interfacial failure load and fracture initiation site for
      simulated resin bonded ceramic restorations. METHODS: Layered disks were
      fabricated using soda lime glass to simulate porcelain and fiberglass to
      represent dentin. These materials were selected due to their approximate elastic
      modulus to porcelain or dentin. In addition, soda lime glass allowed for
      visualization of crack initiation. Glass microscope slides (1.2 mm thick) were
      sectioned into 1-mm2 specimens. The frosted portions of the slides were used as
      the rough or sandblasted group and the clear areas were used as the smooth or
      polished group. All surfaces were either cleaned or etched. Prepared surfaces
      were divided into eight groups and bonded to the substrates using Optibond Solo
      Plus (SDS Kerr, Orange, CA) and Nexus resin cement (SDS Kerr). Support substrates
      were made from 5-mm slices of fiberglass rods (1/2 in. diameter). Vertical loads
      were applied to the layered disks with a 20-mm spherical indenter at a cross-head
      speed of 0.05 mm/min. Observations were made using 10x magnification with a video
      monitor. Load magnitudes were recorded at the time of crack initiation. Weibull
      parametric survival analysis and the effect likelihood ratio test were performed
      on the failure initiation load data to determine significant differences at the
      0.05 level. RESULTS: Mean failure initiation loads ranged from 273.6 to 341.9N
      for the rough specimens and from 1056.5 to 2980.2N for the smooth samples.
      According to the Weibull parametric survival analysis and the effect likelihood
      ratio test, surface roughness and surface etch significantly influenced failure
      initiation loads. Smoother surfaces tolerated much greater contact loads before
      failure initiation. SIGNIFICANCE: The clinical performance of all-ceramic
      restorations may be improved with smoother internal surfaces. Etching
      significantly increases survival for restorations with smooth internal surfaces.

PMID- 16081155
TI  - Nucleation and growth of calcium phosphate on amine-, carboxyl- and hydroxyl
      silane self-assembled monolayers.
AB  - Upon implantation, calcium phosphate (Ca-P) surfaces form on materials that are
      bone bioactive. In this study, the evolving surface characteristics associated
      with calcium phosphate precipitation are modeled using self-assembled monolayers
      (SAMs), in a one-step nucleation process. SAMs were used to create amine (-NH2),
      carboxyl (-COOH) and hydroxyl (-OH) functionalized surfaces by grafting 3
      aminopropyltriethoxysilane, 3-triethoxysilylpropyl succinic anhydride and
      glycidoxypropyl tri-methoxysilane, respectively, onto oxidized silicon wafers.
      The SAM surfaces were characterized using ellipsometry to establish the presence
      of grafted molecules. On the surfaces incubated in simulated physiological fluids
      for 7 days, the thickness of Ca-P layer grew slowly over the first few hours,
      increasing strongly between 1 and 5 days and then slowed down again. FTIR showed
      the dependence of calcium phosphate morphology on the type of surface groups,
      with stronger P-O bands seen on the OH-terminated surface. SEM analysis showed
      dispersed Ca-P precipitates on the -COOH and -OH terminated surfaces after 1 day
      immersion. After 7 days, all SAM surfaces were covered with uniformly dispersed
      and denser Ca-P precipitates. The underlying Ca-P layer showed cracks on the -NH2
      terminated surface. Rutherford backscattering spectrometry (RBS) data analysis
      confirmed that Ca/P ratio is in excellent agreement with the theoretical value of
      1.67 for hydroxyapatite. X-ray diffraction (XRD) analysis also showed evidence of
      apatite formation on all the surfaces, with stronger evidence on the -OH
      terminated surface. Highly porous Ca-P precipitates were observed on the SAM
      surfaces portrayed by the AFM scans with nanoscale RMS roughness. Thus, using
      highly controlled surface chemistry, under physiological conditions, in vitro,
      this study demonstrates that a hydroxylated surface enhances Ca-P nucleation and
      growth relative to other surfaces, thereby supporting the concept of its
      beneficial effect on bone tissue formation and growth.

PMID- 16081156
TI  - No evidence of mutations of the PSMB5 (beta-5 subunit of proteasome) in a case of
      myeloma with clinical resistance to Bortezomib.

PMID- 16081157
TI  - Mutation of FLT3 is not a general phenomenon in CD117-positive T-ALL.

PMID- 16081158
TI  - Aggression, and some related psychological constructs (anger, hostility, and
      impulsivity); some comments from a research project.
AB  - The purpose of the present study was: first, to offer a few theoretical
      considerations on the concept of human aggression and its main types; and second,
      to analyse the relationship between those types of aggression and other related
      psychological constructs, such as anger, hostility, and impulsivity, summarizing
      the main empirical results of our research in progress. In order to assess their
      eventual correlations, several self-report techniques were compared: (a) AQ, used
      to measure several kinds of aggression, anger, and hostility; (b) CAMA, a
      questionnaire already used in a variety of cultures, for measuring attitudes
      toward interpersonal aggression in different instrumental and hostile situations;
      (c) ASQ, an instrument for measuring experienced anger and its expression in
      assertive or aggressive ways; and (d) BIS, used to prove three impulsiveness sub
      traits: motor, attentional, and non-planning impulsiveness. The different
      definitions of aggression may be grouped according to whether the primary goal is
      distress or harm, focusing primarily on the objective infliction of harm, or on
      the subjective intention of harming. Most classifications in the literature show
      two kinds of aggression, even if different names are used: Hostile Aggression
      (among other names it is also known as 'reactive, impulsive, or affective') is an
      act primarily oriented to hurt another individual; and Instrumental Aggression
      (also known as 'proactive, premeditated, or predative') is a means or tool for
      solving problems or for obtaining a variety of objectives. As predicted, there
      was a positive correlation between experience and expression of anger. Anger
      involved physiological arousal and prepared for aggression. Anger and
      impulsiveness were also positively correlated with hostile aggression, but not
      with instrumental aggression. In the case of impulsiveness, non-planning
      impulsiveness was positively correlated with some situations related to hostile
      aggression, such as emotional agitation or lack of communication, but not with
      instrumental one. Finally, hostility positively correlated with anger and
      different kinds of aggression, but not its degree of justification. In sum,
      aggression can be reflected in the different personality constructs, measured by
      self-reports.

PMID- 16081159
TI  - Anti-GQ1b-negative Miller-Fisher syndrome with lower cranial nerve involvement
      from parasinusoidal aspergilloma.
AB  - Miller-Fisher syndrome (MFS) typically presents with ophthalmoplegia, ataxia, and
      areflexia. Atypical MFS additionally includes bulbar impairment, affection of the
      limbs, or abortive presentations. Mostly, MFS follows an infection with
      Campylobacter jejunii. Aspergilloma has not been reported to trigger MFS. In a 48
      year-old male tiredness, tinnitus, otalgia, parietal hyperaesthesia, coughing,
      plugged nose, hypoacusis, globus sensation, epipharyngeal pain, dysarthria,
      hypogeusia, arthralgia, lid cloni, facial hypaesthesia and tooth ache
      consecutively developed. There were occasional lid cloni, left-sided facial
      hypaesthesia, reduced gag reflex, divesting soft palate, and absent tendon
      reflexes. CSF investigations revealed normal cell-count but increased protein.
      Antibodies against GM1 and GQ1b were negative. Atypical MFS was diagnosed.
      Otolaryngological examinations revealed chronic sinusitis maxillaris from an
      aspergilloma. After immunoglobulins and resectioning of the aspergilloma,
      neurological abnormalities disappeared within 19d. MFS may manifest as unilateral
      lower cranial nerve lesions without affection of the upper cranial nerves or
      ataxia. Atypical MFS may be triggered by parasinusoidal aspergilloma.

PMID- 16081160
TI  - An esophageal mass with coexistent Mycobacterium chelonae and Candida albicans
      infections in an immunocompetent adult.
AB  - Mycobacteria chelonae was originally included in group IV of Runyon's
      classification of atypical mycobacteria. This rapidly growing environmental
      organism often caused infections in immunocompromised hosts. Candida albicans is
      a ubiquitous micro-organism and frequently isolated from the gastrointestinal
      tract. These two micro-organisms seldom cause esophageal diseases in healthy
      humans. We report a case of a fruit farmer with a submucosa tumor of distal
      esophagus caused by coexistence of M. chelonae and C. albicans infections, which
      was successfully treated by surgical resection and following antimicrobial
      regimens postoperatively.

PMID- 16081161
TI  - Targeting memory Th2 cells for the treatment of allergic asthma.
AB  - Th2 memory cells play an important role in the pathogenesis of allergic asthma.
      Evidence from patients and experimental models indicates that memory Th2 cells
      reside in the lungs during disease remission and, upon allergen exposure, become
      activated effectors involved in disease exacerbation. The inhibition of memory
      Th2 cells or their effector functions in allergic asthma influence disease
      progression, suggesting their importance as therapeutic targets. They are
      allergen specific and can potentially be suppressed or eliminated using this
      specificity. They have distinct activation, differentiation, cell surface
      phenotype, migration capacity, and effector functions that can be targeted
      singularly or in combination. Furthermore, memory Th2 cells residing in the lungs
      can be treated locally. Capitalizing on these unique attributes is important for
      drug development for allergic asthma. The aim of this review is to present an
      overview of therapeutic strategies targeting Th2 memory cells in allergic asthma,
      emphasizing Th2 generation, differentiation, activation, migration, effector
      function, and survival.

PMID- 16081162
TI  - A modified Golgi staining protocol for use in the human brain stem and
      cerebellum.
AB  - The Golgi silver-impregnation method established itself as an important technique
      for distinguishing morphology at the individual neuron level. This technique has
      been especially useful for studying human neuroanatomy because it works on
      postmortem tissue but it is also unreliable and capricious. In this report, we
      describe a simple technique that was applied to human autopsy and tissue-bank
      material yielding useful results for the study of neuronal morphology in the
      brain stem and cerebellum. Human adult brain stems had been immersion-fixed in
      formalin for a period of time ranging from weeks to months. Brain stem tissue was
      cross-sectioned into 3-5mm thick slabs, centered about the cochlear nucleus.
      Slabs were processed under continuous vacuum (22-26 in. of Hg), a procedure that
      promoted penetration of reagents into the tissue. Tissue was sectioned using a
      Vibratome and mounted for light microscopy. The results demonstrated improved
      staining of neurons in the brain stem. Staining of the large synaptic endings of
      auditory nerve fibers called end bulbs of Held in the cochlear nucleus was
      especially evident. These results suggest that an age-graded series could be
      conducted to describe the development of these large auditory endings in humans.

PMID- 16081163
TI  - Blocking polysynaptic inhibition via opioid receptor activation isolates
      excitatory synaptic currents without triggering epileptiform activity in
      organotypic hippocampal slices.
AB  - The abundance of synaptic connectivity in the cultured hippocampal slice
      preparation allows measurements of the unitary excitatory connection between
      pairs of pyramidal neurons using simultaneous presynaptic and postsynaptic
      intracellular recordings. However, the useful yield of these recordings can be
      greatly reduced by the presence of polysynaptic inhibition that occludes the
      measurement of the monosynaptic excitatory postsynaptic current (EPSC). We have
      found that the traditional method of eliminating contaminating synaptic
      inhibition with GABA receptor antagonists is of limited usefulness because the
      recurrent excitatory connections in organotypic slices cause epileptiform
      bursting in the absence of inhibitory function. This bursting obscures EPSCs to
      an even greater extent than the normally occurring polysynaptic inhibitory
      transmission. Here, we report a new method for isolating monosynaptic EPSCs using
      the mu-opioid agonist peptide DAMGO to reduce polysynaptic inhibition during
      these recordings. Activation of mu-opioid receptors is known to hyperpolarize
      inhibitory neurons. We found that DAMGO application reduces the amplitude and
      frequency of polysynaptic inhibition, allowing isolation of the excitatory
      connection between the two neurons being recorded. Furthermore, because
      inhibitory function is not completely eliminated by DAMGO application,
      epileptiform bursting very rarely develops. Therefore, the use of DAMGO to
      prevent polysynaptic inhibition without causing epileptiform bursting provides a
      useful tool to substantially increase the yield of experiments measuring the
      unitary excitatory connection between pyramidal neurons in the cultured
      hippocampal slice preparation.

PMID- 16081164
TI  - Development and validation of a questionnaire for anxiety and depression in
      Pakistan.
AB  - BACKGROUND: Currently clinicians and researchers in Pakistan have to use
      translated western instruments to screen for anxiety and depressive disorders.
      This study investigated the local idioms of emotional distress in Pakistan to
      develop a culturally valid and easy-to-use instrument to screen for common mental
      disorders in general clinical settings. METHODS: A systematic survey was
      conducted of psychiatric case notes of patients attending clinics in Peshawar and
      Lahore, diagnosed with anxiety or depressive disorders, to identify the range of
      common idioms of psychological distress. A pilot version of the questionnaire was
      refined and validated among a composite sample of 330 patients in inpatient,
      outpatient and rural community settings. ICD-10 Diagnostic Criteria for Research
      were used to define cases and patients' relatives acted as normal controls.
      RESULTS: The pilot version of the questionnaire was reduced to 42 items based on
      odds ratios between cases and controls. Anxiety symptoms were generally reported
      by depressed patients, but not vice versa. Finally 30 items were selected, in two
      sub-scales. This final version achieved sensitivity, specificity, and positive
      and negative predicted values of over 90% when comparing cases and controls.
      LIMITATIONS: This questionnaire was based on what patients tell doctors and may
      not capture the entire repertoire of local idioms of distress. The validation
      study was conducted only in an Urdu/Punjabi speaking population, in Lahore and
      surrounding areas. CONCLUSIONS: The Pakistan Anxiety and Depression Questionnaire
      consists of an anxiety/depression scale and a depression scale, each of 15 items.
      It demonstrates excellent validity as screening instrument for anxiety and
      depressive disorders in clinical settings in Pakistan.

PMID- 16081165
TI  - Signaling pathways involved with serotonin1A agonist-mediated neuroprotection
      against ethanol-induced apoptosis of fetal rhombencephalic neurons.
AB  - Previously, this laboratory demonstrated that developing serotonin (5-HT) neurons
      and other fetal rhombencephalic neurons are reduced by in vivo and in vitro
      exposure to ethanol, effects that are related to ethanol's augmentation of
      apoptosis. We also found that 5-HT1A agonists diminished the ethanol-associated
      reduction of 5-HT neurons and other fetal rhombencephalic neurons by attenuating
      the pro-apoptotic effects of ethanol. Presently, we investigated the hypothesis
      that the protective/anti-apoptotic effects of a 5-HT1A agonist on fetal
      rhombencephalic neurons are mediated by activation of the phosphatidylinositol 3'
      kinase (PI-3K) and/or the mitogen-activated protein kinase kinase (MAPKK)
      pathway. Apoptotic and non-apoptotic fetal rhombencephalic neurons were
      quantitated in primary cultures that were treated with 50 mM ethanol and with 100
      nM of a 5-HT1A agonist such as 8-OH-DPAT [8-hydroxy 2-(di-n
      propylamino)tetralin], ipsapirone, or buspirone. Analysis of neurons stained with
      Hoechst 33342 demonstrated the anti-apoptotic effects of 5-HT1A agonists and
      implicated the involvement of the PI-3K pathway and possibly the MAPKK pathway
      with the protective effects of these drugs. The protective effects were blocked
      by a 5-HT1A antagonist (WAY 100635), an inhibitor of PI-3K (LY294002), and an
      inhibitor of MAPKK (PD98059). Western blot analyses showed that ethanol treatment
      reduces basal pAkt levels. These analyses also provide support for the
      involvement of the PI-3K pathway; ipsapirone stimulated the phosphorylation of
      Akt in control and ethanol-treated neurons, and these effects were antagonized by
      LY294002.

PMID- 16081166
TI  - alpha2-Adrenergic agonists antagonise the anxiolytic-like effect of
      antidepressants in the four-plate test in mice.
AB  - Selective serotonin reuptake inhibitors (SSRIs) and serotonin/noradrenaline
      reuptake inhibitors (SNRIs) has been reported to be efficient in anxiety
      disorders. Some animal models have demonstrated an anxiolytic-like effect
      following acute administration, however, it is not yet known how noradrenergic
      receptors are implicated in the therapeutic effects of antidepressants (ADs) in
      anxiety. The effects of two alpha(2)-adrenoceptor agonists (clonidine, guanabenz)
      on anxiolytic-like effect of two SSRIs (paroxetine and citalopram) and two SNRIs
      (venlafaxine and milnacipran) were evaluated in the four-plate test (FPT) in
      mice. Paroxetine (4 mg/kg), citalopram (8 mg/kg), venlafaxine (8 mg/kg), and
      milnacipran (8 mg/kg) administered intraperitoneally (i.p.) increased the number
      of punishments accepted by mice in the FPT. Clonidine (0.0039-0.5 mg/kg) and
      guanabenz (0.03-0.5mg/kg) had no effect on the number of punishments accepted by
      mice. Clonidine (0.03 and 0.06 mg/kg) and guanabenz (0.125 and 0.5 mg/kg) (i.p. 
      45 min) reversed the anti-punishment effect of paroxetine, citalopram,
      venlafaxine and milnacipran (i.p. -30 min). But if the antidepressants are
      administered 45 min before the test and alpha(2)-adrenoceptor agonists 30 min
      before the test, alpha(2)-adrenoceptor agonists failed to alter the anti
      punishment effect of antidepressants. The results of this present study indicate
      that alpha(2)-adrenoceptor agonists antagonise the anxiolytic-like effect of
      antidepressants in mice when they are administered 15 min before the
      administration of antidepressant suggesting a close inter-regulation between
      noradrenergic and serotoninergic system in the mechanism of SSRIs and SNRIs in
      anxiety-like behaviour.

PMID- 16081167
TI  - Plasma transforming growth factor beta1, metalloproteinase-1 and tissue inhibitor
      of metalloproteinases-1 in acute viral hepatitis type B.
AB  - AIM: Antiproliferative, pro-apoptotic and immunosuppressive activity effects
      suggest crucial role of transforming growth factor (TGF)-beta1, metalloproteinase
      (MMP)-1 and its tissue inhibitor (TIMP)-1 in the pathogenesis of acute liver
      injury that in some patients precede development of chronic liver diseases and
      fibrogenesis. The aim of this study was to evaluate effect of acute HBV infection
      on plasma TGF-beta1, MMP-1 and TIMP-1 levels. METHODS: TGF-beta1, MMP-1 and TIMP
      1 plasma concentrations were measured with an enzyme immunoassay in 39 patients
      with acute viral hepatitis type B. Baseline measurement was performed within the
      first week of jaundice and then weekly up to the fourth week of the disease.
      Results were compared to baseline and normal values and to liver function tests.
      RESULTS: Plasma concentrations of TGF-beta1, TIMP-1 and MMP-1 were significantly
      elevated in the first week of acute viral B hepatitis in comparison to normal.
      Analysis of individual values demonstrated significant positive correlation
      between plasma concentrations of TGF-beta1 and TIMP-1. There was no correlation
      between MMP-1 and TGF-beta1 or TIMP-1. Significant correlation was demonstrated
      between both TGF-beta1 and ALT or AST as well as between TIMP-1 and ALT, AST or
      bilirubin. Elevated baseline levels of both TGF-beta1 and TIMP-1 decreased
      gradually in consecutive weeks of the disease. TGF-beta1 but not TIMP-1 plasma
      concentrations were significantly lower in 3rd and 4th week than baseline values.
      MMP-1 concentration remained on baseline level in the 2nd week of the disease.
      However in the 3rd week its values increased suddenly but the significant
      difference in comparison to baseline was observed only in 4th week. CONCLUSIONS:
      These results indicate important role of TGF-beta1, TIMP-1 and MMP-1 in acute
      viral hepatitis, that seems to be connected first of all with hepatocytes damage.
      Their role in extracellular matrix metabolism during acute liver injury needs
      further evaluation.

PMID- 16081168
TI  - Cloning of GLUT3 cDNA from Atlantic cod (Gadus morhua) and expression of GLUT1
      and GLUT3 in response to hypoxia.
AB  - A putative facilitative glucose transporter, GLUT3, cDNA was cloned from Atlantic
      cod. It is ubiquitously expressed, with substantial levels in kidney. The 519 aa
      protein has the highest sequence identity (66.3%) to grass carp GLUT3. Atlantic
      cod were exposed to a hypoxic challenge (45% DO2) for 24 h and the effects on
      GLUT1 and GLUT3 expression assessed. GLUT1 expression in gill is upregulated;
      however, in spleen, there is a significant decrease in both GLUT1 and GLUT3
      expression. The increase in GLUT1 mRNA is considered to be associated with an
      increased energy demand on gill, whereas, the decrease in gene expression in
      spleen potentially reflects a general decrease in rates of transcription.

PMID- 16081169
TI  - Expression of SERK family receptor-like protein kinase genes in rice.
AB  - Some SERK-family receptor-like protein kinase genes have been shown to confer
      embryonic competence to cells. In this study, we isolated two novel rice genes,
      OsSERK1 and OsSERK2, belonging to the SERK-family. OsSERK2 showed constitutive
      expression. The OsSERK1 promoter showed reporter gene activities in some specific
      tissues in a germinating seed, leaf and root, but not in a developing embryo.
      This promoter activity suggests that OsSERK1 may have roles in non-embryonic
      tissues rather than in the embryo.

PMID- 16081170
TI  - D-3 phosphoinositides of the ciliate Tetrahymena: characterization and study of
      their regulatory role in lysosomal enzyme secretion.
AB  - Phosphatidylinositol 3-phosphate, PtdIns3P, is a phosphoinositide which is
      implicated in regulating membrane trafficking in both mammalian and yeast cells.
      It also serves as a precursor for the synthesis of phosphatidylinositol 3,5
      bisphosphate, PtdIns3,5P2, a phosphoinositide, the exact functions of which
      remain unknown. In this report, we show that these two phosphoinositides are
      constitutive lipid components of the ciliate Tetrahymena. Using HPLC analysis,
      PtdIns3P and PtdIns3,5P2 were found to comprise 16% and 30-40% of their relevant
      phosphoinositide pools, respectively. Treatment of Tetrahymena cells with
      wortmannin (0.1-10 microM) resulted in the depletion of PtdIns3P and PtdIns3,5P2
      without any effect on D-4 phosphoinositides. Wortmannin was further used for the
      investigation of D-3 phosphoinositide involvement in the regulation of lysosomal
      vesicular trafficking. Incubation of Tetrahymena cells with wortmannin resulted
      in enhanced secretion of two different lysosomal enzymes without any change in
      their total activities. Experiments performed with a T. thermophila secretion
      mutant strain verified that the wortmannin-induced secretion is specific and it
      is not due to a diversion of lysosomal enzymes to other secretory pathways.
      Moreover, experiments performed with a phagocytosis-deficient T. thermophila
      strain showed that a substantial fraction of wortmannin-induced secretion was
      dependent on the presence of functional phagosomes/phagolysosomes.

PMID- 16081171
TI  - Effects of cognitive function on functional decline among community-dwelling non
      disabled older Japanese.
AB  - This study examined whether cognitive impairment, falls, and urinary incontinence
      (UI) were independent predictors of functional decline using a 2-year observation
      of a non-disabled older Japanese cohort living in a community from 1999 to 2001.
      A total of 139 men and 214 women aged 70-94 years at the baseline who were
      independent in both activities of daily living (ADL) and instrumental activities
      of daily living (IADL) were analyzed in this study. Independent variables, such
      as cognitive impairment, falls, UI, and other possible factors associated with
      functional decline were obtained from an interview survey at the baseline. A
      dependent variable was functional status in ADL and IADL obtained at the time of
      the 2-year follow-up. During the 2-year follow-up, cognitive function was a
      significant predictor for both IADL dependence and ADL and/or IADL dependence.
      Using a group of subjects with Mini Mental State Examination (MMSE) scores of 30
      27 points as a reference group, a significant correlation was identified between
      lower MMSE scores and an increased odds ratio for functional decline. Lower
      cognitive function was a significant predictor of functional decline, even among
      those older Japanese whose cognitive function was deemed to be within the normal
      range.

PMID- 16081172
TI  - Power spectral analysis of heart rate variability as a predictive test in
      choosing the most effective length for tilt-training.
AB  - BACKGROUND: In patients with refractory neurally mediated syncope, tilt training-
      standing motionless against a wall for increased periods of time per day over one
      month--can often eliminate recurrent episodes and reduce presyncopal symptoms. We
      designed dual retrospective and prospective studies to assess cardiovascular
      autonomic function in subjects with recurrent syncope and identify the most
      effective length of tilt training between one and three months. METHODS AND
      RESULTS: In the retrospective study, before tilt training, and in the prospective
      study, before and after training, all subjects underwent a recording for short
      term spectral analysis of heart rate and systolic blood pressure variability.
      Before tilt-training, autonomic nervous system function differs in patients with
      recurrent neurally mediated syncope who respond to tilt training for one month
      and those who do not. "Responders", patients experiencing no episodes of syncope
      during the 12-month follow-up, had higher low-frequency power of RR (LF(RR)) (p <
      0.05) and LF(RR) in normalized units (NU) (p < 0.001) and lower high-frequency
      power (HF(RR)) (p < 0.05) and HF(RR)NU (p < 0.001) than "non-responders",
      patients reporting at least one syncopal episode during the 12-month follow-up.
      In the retrospective study, no difference was found between spectral data for
      "non-responders" with positive responses to tilt test with and without nitro
      derivatives. Prolonging tilt-training to three months increased the number of
      responders (late-responders) by 80% (p < 0.001) and power spectral analysis of
      heart rate variability (HRV) before tilt training can identify late-responders by
      their low LF(RR)NUs (<40) and high HF(RR)Nus (>60). Furthermore in late
      responders, tilt training brings about a change in cardiovascular autonomic
      function: at 3 months, LF(RR)NUs increase and HF(RR)NU diminish. CONCLUSION:
      Power spectral analysis of HRV seems to be a useful tool to preselect patients
      who are most likely to benefit from prolonged therapy, thus increasing
      compliance.

PMID- 16081173
TI  - Effects of host density on furunculosis epidemics determined by the simple SIR
      model.
AB  - To determine the transmission dynamics of furunculosis, Chinook salmon,
      Oncorhynchus tshawytscha held at various densities were challenged with a single
      infectious fish. Data from the in vivo experiments were compared to predicted
      values from a susceptible--infected--removed (SIR) model. Seven different
      densities were tested including 9.13, 4.56, 0.72, 0.36, 0.19, 0.06 and 0.03
      fish/L and each produced different transmission coefficients (beta) of 0.01,
      0.019, 0.0051, 0.0076, 0.0001, 0.0005 and 0.00, respectively. Furunculosis
      related mortality rates decreased as density of the host decreased. Mortality
      rates at the highest fish densities where disease specific mortality (DSM) was
      observed were 0.42, 0.44, 0.18 and 0.02 infected animals per day. The natural
      mortality rate also followed a similar pattern with 0.005, 0.005, 0.001, 0.005,
      0.0001, 0.000 and 0.000 surviving animals per day. The results indicated that the
      transmission coefficient and the DSM of furunculosis was dependent on host
      density. It is possible that fish behavioral changes at the lower densities
      caused the reproductive rate of disease to be persistent even at very low
      densities. In summary, the simple SIR model suggested that low mortality does not
      always mean low prevalence of furunculosis in a given population. This is the
      first study evaluating host density as a risk factor for fish diseases using
      experimental furunculosis data.

PMID- 16081174
TI  - Real time PCR using TaqMan and SYBR Green for detection of Enterobacter sakazakii
      in infant formula.
AB  - Enterobacter sakazakii is an emerging pathogen that causes meningitis,
      bacteremia, sepsis, and necrotizing enterocolitis in neonates and children.
      Powdered milk-based infant formulas have been associated with the E. sakazakii
      related outbreaks in premature or other immunocompromised infants. In this study,
      we developed two real time PCR assays using TaqMan and SYBR Green to identify the
      pathogen after selective enrichment in mLST and BHI. The accuracy of two
      detections was tested by 35 strains of E. sakazakii and 88 non-E. sakazakii
      bacterial strains. The results showed that all of these E. sakazakii strains were
      positive reaction to the detections and all of the non-E. sakazakii strains were
      negative. The newly developed assays enable us to detect 1.1 CFU/100 g infant
      formula. And both of the assays can be accomplished within 2 business days.
      Compared to the traditional detection, the real time PCR procedures are quicker
      and simpler. In this study, we also developed a new method to design the primers,
      which can support multiple real time PCR with one pair of primers in SYBR Green
      detection. The detection methods are more sensitive and effective based on Two-Tm
      Value of PCR.

PMID- 16081175
TI  - Flow cytometric analysis of bacteria- and virus-like particles in lake sediments.
AB  - Flow cytometry (FCM) was successfully used to analyze freshwater bacteria and
      viruses in lake sediments after relatively simple sample treatment and
      optimization of dilution/fixation/staining procedures. Biological particles from
      Lakes Geneva and Bourget were first separated from the sediments by using both
      Sodium Pyrophosphate (0.01 M final concentration) and Polyoxyethylene-Sorbitan
      Monooleate (10% final concentration) and sonicating for 3 min in a water bath.
      The best results (based on FCM signature and the highest virus and bacterial
      yields from the sediments) were obtained by formaldehyde fixation carried out
      within less than one hour (2% final concentration, vs. no fixation or using
      glutaraldehyde at different concentrations), SYBR-Green II staining (x1/20,000
      stock solution concentration, vs. use of SYBR-Gold and SYBR-Green I dyes at
      different concentrations). There was a considerable loss of particles after only
      a few days of storage at either 4 or -22 degrees C. For FCM analysis, the samples
      were diluted in Tris-EDTA buffer (pH 8) and heated for 10 min at 75 degrees C
      after incubating for 5 min in the dark. The bacterial and viral counts paralleled
      those obtained using epifluorescence microscopy (EFM), but EFM always gave lower
      counts than FCM. Analysis of the distribution of the viruses in the water column
      and in the sediments of Lakes Bourget revealed a marked gradient, with larger
      quantities in the top layer of the sediment than in the water above it. These
      results are discussed, as well as the possible novel application of flow
      cytometry in the study of aquatic viral ecology.

PMID- 16081176
TI  - Improving the 'how' and 'what' decisions of elite table tennis players.
AB  - Training methods in sport usually focus on improving either technical or tactical
      aspects of performance, ignoring the fact that successful performance requires
      the athlete to simultaneously decide what movement to perform and how it should
      be executed. Young elite table tennis players were trained, in a first phase, to
      improve their forehand and backhand movements and, in a second phase, to make a
      tactical switch between forehand and backhand movements. Half of the players took
      part in behavioral training focusing on how to perform the required movements,
      whereas half received additional video feedback about their technical and
      tactical performance (decision training). The results indicate that improvements
      of how decisions (techniques) and what decisions (tactics) can occur as a
      consequence of combining technical and tactical training. These results were
      stable in delayed Post-test analyses of competitive matches. It was concluded
      that a combination of both technical and tactical training is beneficial to elite
      table tennis performers, particularly during early seasonal training programs.

PMID- 16081177
TI  - Depolarizing effect of GABA in horizontal cells of the rabbit retina.
AB  - Gamma-amino butyric acid (GABA) has been characterized as an inhibitory
      neurotransmitter acting through chloride mediated channels in the adult nervous
      system. Using gramicidin-perforated patch clamp recordings from horizontal cells
      dissociated from the retinas of adult rabbits, we found that GABA is able to
      induce cell depolarization. Ionic currents induced by GABA in dissociated
      horizontal cells showed a reversal potential close to -30 mV. This value is more
      positive than the resting potential of these cells (ca. -70 mV). Therefore,
      according to the Nernst equation, the intracellular chloride concentration in
      horizontal cells was estimated to be of 44 mM. The depolarizing effect of GABA at
      the dendrites of horizontal cells may serve to shape the center-surround
      organization of the receptive fields in retinal cells, thereby securing the shape
      discrimination of visual input.

PMID- 16081178
TI  - Phenotypic and genotypic comparisons reveal a broad distribution and
      heterogeneity of hemolysin BL genes among Bacillus cereus isolates.
AB  - The presence of hemolysin BL (HBL; components L(2), L(1), and B)-encoding genes
      (hblC, hblD, and hblA) from 339 Bacillus cereus strains isolated in Thailand was
      determined. PCR analysis showed that all three hbl genes were detected in 222
      strains (65.5%). Two, one or no hbl genes were detected in 3 (0.9%), 6 (1.8%),
      and 108 (31.8%) strains, respectively. Among the 222 strains in which all three
      hbl genes were detected, 210 (61.9%) displayed discontinuous hemolysis (DH)
      characteristic of HBL producers, while 12 (3.5%) showed continuous hemolysis (CH)
      on sheep blood agar. Among strains in which none of the hbl genes was detected,
      97 (28.6%) displayed CH while 11 (3.2%) did not show hemolytic activity. Three
      strains in which two hbl genes were detected showed CH. hblC was present in five
      of six strains where only one hbl gene was detected, and all of them (designated
      SS-00-15, TG-00-06, TG-00-14, F-00-25, and NR-01-49) showed DH. The HpaII
      restriction profiles of PCR fragments amplified from the hblC-A region in these
      five strains using hblC forward (FHC) and hblA reverse (RHA(2)) primers displayed
      heterogeneous patterns, which indicated sequence variation. Western blot analysis
      using polyclonal antibodies (Pab) raised against HBL components purified from
      strain F837/76 showed that three of the five strains produced all three
      components, whereas strain TG-00-06 did not give a signal for any component, and
      strain TG-00-14 produced B and L(1) but not L(2). The production of L(2) by these
      five strains was further analyzed using the Oxoid RPLA test. Three strains gave
      high titers (>64) whereas strains TG-00-06 and TG-00-14 showed lower titers of 16
      and 32, respectively. The data show that HBL-encoding genes are widely
      distributed among B. cereus isolated in Thailand and there is a high degree of
      heterogeneity in both the genes and proteins. This is the first report of a B.
      cereus strain showing DH in which all three hbl genes and their proteins were not
      detected by both PCR primers and antibodies derived from prototype and type
      strains. The data also suggest that the L(2) component from strains TG-00-06 and
      TG-00-14 may be antigenically very different from that of most B. cereus
      isolates.

PMID- 16081179
TI  - A new approach for selection of Oenococcus oeni strains in order to produce
      malolactic starters.
AB  - The lactic acid bacterium Oenococcus oeni, mainly responsible for malolactic
      fermentation (MLF), is used in new winery process as starter culture for direct
      inoculation. The difficulty to master MLF according to the wine led us to search
      a new approach to select effective O. oeni strains. Biochemical and molecular
      tests were performed in order to characterize three strains of O. oeni selected
      for malolactic starter elaboration. Malolactic and ATPase activities that
      appeared as a great interest in MLF were measured and the expression of a small
      heat shock protein Lo18 was evaluated by immunoblotting and real-time PCR. These
      results were correlated with the performances of strains in two red wines.
      Physiological and molecular characteristics of the three strains showed
      significant differences for the global malolactic activity on intact cell at pH
      3.0 and at the level of induction of the small heat shock protein Lo18. These two
      parameters appeared of interest to evaluate in the ability of O. oeni strains to
      survive into wine after direct inoculation and to perform MLF. Indeed, a tested
      strain that presented the highest malolactic activity on intact cells at pH 3.0
      and a high level of Lo18 induction showed a high growth rate and a high specific
      kinetic of malate consumption. The techniques used in this work carry out more
      quickly and more reliable than usual for the selection of effective strains
      intended for direct inoculation in wines.

PMID- 16081180
TI  - Fate of Escherichia coli O157:H7 during the processing and storage of Ergo and
      Ayib, traditional Ethiopian dairy products.
AB  - The long-term survival of E. coli O157:H7 in acid foods is well documented. This
      prompted us to evaluate the organism's survival during the making of Ergo, a
      traditional Ethiopian sour milk and Ayib, a traditional Ethiopian cottage cheese
      and during storage of these products at both ambient and refrigeration
      temperatures. E. coli O157:H7 test strains were separately inoculated into milk
      at initial levels of log10 3 cfu/ml. Levels of E. coli O157:H7 in the absence of
      lactic acid bacteria (LAB) reached log10 8.4 cfu/ml at 24 h as the pH dropped to
      5.6 +/- 1.0. In milk inoculated with LAB (log10 6.4 cfu/ml) and E. coli O157:H7
      (log10 3 cfu/ml), levels of LAB were log10 9.6 cfu/ml and 9.4 cfu/ml at 24 h and
      72 h, respectively, and the pH values were 3.5 and 3.9, respectively. In the
      presence of LAB, E. coli O157:H7 grew to log10 6.5 cfu/ml at 24 h, with the
      levels decreasing to log10 3.2 cfu/ml at 72 h. Post-fermentation inoculation of
      E. coli O157:H7 in Ergo at an initial level of log10 3 cfu/ml, resulted in
      complete elimination of test organisms at 6 h at ambient temperature storage, but
      they were recovered until 72 h at refrigerated storage. At a higher initial
      inoculum level (log10 6 cfu/ml) of the E. coli O157:H7, the counts decreased by 4
      logs within 12 h (pH 4.2) at ambient temperature storage, and complete
      elimination was observed at 36 h (pH 4.0). At refrigeration temperature, counts
      at 72 h were between 2.2 and 3.5 log cfu/ml for the different strains. During
      Ayib processing, E. coli O157:H7 in souring milk increased by 3 logs in 24 h,
      with a slight reduction being observed at 36 h. The pH dropped to 4.3 during this
      time. The numbers of E. coli O157:H7, immediately after curd cooking, were below
      detectable levels, but could be recovered by enrichment. Complete inactivation
      was observed on 24 h after curd cooking. When E. coli O157:H7 was inoculated into
      steam-treated Ayib (pH 4.2-4.3) at levels of log10 6.0-6.7 cfu/g and maintained
      at ambient temperatures, there was a gradual decrease in numbers to 3.7-4.3 logs
      by day 3. After day 7, pH values were 3.8-3.9 and E. coli O157:H7 was only
      detectable after enrichment. E. coli O157:H7 strain MF-1847 was completely
      inactivated by day 9, but the other two strains could still be recovered by
      enrichment at this time. At refrigeration storage, decrease in count of the test
      strains was gradual and counts at day 8 and 9 were >4 log cfu/g. As Ergo is
      preferably consumed soon after (24 h) fermentation, traditional fermentation of
      Ergo would not guarantee that E. coli O157:H7 can be controlled and, therefore,
      Ergo can be a potential health hazard if prepared from milk contaminated with E.
      coli O157:H7.

PMID- 16081181
TI  - Flow modelling within a scaffold under the influence of uni-axial and bi-axial
      bioreactor rotation.
AB  - The problem of donor scarcity has led to the recent development of tissue
      engineering technologies, which aim to create implantable tissue equivalents for
      clinical transplantation. These replacement tissues are being realised through
      the use of biodegradable polymer scaffolds; temporary/permanent substrates, which
      facilitate cell attachment, proliferation, retention and differentiated tissue
      function. To optimise gas transfer and nutrient delivery, as well as to mimic the
      fluid dynamic environment present within the body, a dynamic system might be
      chosen. Experiments have shown that dynamic systems enhance tissue growth, with
      the aid of scaffolds, as compared to static culture systems. Very often, tissue
      growth within scaffolds is only seen to occur at the periphery. The present study
      utilises the Computational Fluid Dynamics package FLUENT, to provide a better
      understanding of the flow phenomena in scaffolds, within our novel bioreactor
      system. The uni-axial and bi-axial rotational schemes are studied and compared,
      based on a vessel rotating speed of 35 rpm. The wall shear stresses within and
      without the constructs are also studied. Findings show that bi-axial rotation of
      the vessel results in manifold increases of fluid velocity within the constructs,
      relative to uni-axial rotation about the X- and Z-axes, respectively.

PMID- 16081182
TI  - Finite element analysis of the release of slowly dissolving drugs from
      cylindrical matrix systems.
AB  - Drug release from matrix systems of cylindrical shape is analyzed in detail by
      using the finite element method. The model used combines the Noyes-Whitney and
      diffusion equations, and thus takes the effects of a finite dissolution rate into
      account. The model is valid for all drug solubilities and dissolution rates, and
      allows accurate predictions of the drug release to be made. Anisotropic drug
      transport that may result from the manufacturing process is properly accounted
      for. Model calculations show that a finite dissolution rate may affect the
      release profile significantly, producing an initial delay. The equivalence
      between anisotropic release and isotropic release from a matrix with different
      dimensions is demonstrated. Comparisons are made with the predictions of a
      recently proposed pseudo-steady state (PSS) analysis of drug release from
      cylindrical matrices [Y. Zhou, J. S. Chu, T. Zhou, X. Y. Wu, Modeling of
      dispersed-drug release from two-dimensional matrix tablets, Biomaterials 26
      (2005) 945-952]. This comparison reveals that important discrepancies exist
      between the numerical and analytical results, which are attributed to the
      simplifying assumption made in the PSS analysis that the region containing solid
      drug remains cylindrical in shape throughout the release process. The proposed
      model is shown to describe experimental release data well.

PMID- 16081183
TI  - Enhanced anticancer efficacy of alpha-tocopheryl succinate by conjugation with
      polyethylene glycol.
AB  - Alpha-tocopheryl polyethylene glycol succinate (TPGS) has been used to enhance
      the bioavailability of poorly absorbed drugs and as a vehicle for drug delivery
      systems. In response to recent reports that alpha-tocopheryl succinate (TOS) acts
      as an anticancer agent, we investigated whether its polyethylene glycol (PEG)
      conjugate, TPGS, also possesses anticancer activity. TPGS inhibited the growth of
      human lung carcinoma cells implanted in nude mice, and in an in vitro cell
      culture, even more potently than TOS. The time-dependent uptake of TPGS into
      cells did not differ from that of TOS, indicating that the enhanced antitumor
      efficacy of TPGS was not due to its increased uptake into cells. Compared with
      TOS, TPGS was more effective at inducing apoptosis and the generation of reactive
      oxygen species, suggesting that the superior anticancer efficacy of TPGS is
      associated with its increased ability to induce apoptosis. Our data suggest that
      further studies assessing the potential usefulness of TPGS in cancer therapeutics
      are warranted, since its use as a vehicle in the formulation of anticancer drugs
      may provide an effective way to improve their therapeutic efficacy.

PMID- 16081184
TI  - A versatile family of degradable non-viral gene carriers based on hyperbranched
      poly(ester amine)s.
AB  - A variety of degradable hyperbranched poly(ester amine)s containing primary,
      secondary and tertiary amino groups, were synthesized and evaluated as non-viral
      gene carriers. The polymers were obtained in high yields through a Michael-type
      conjugate addition of diacrylate monomers with trifunctional amine monomers.
      Analysis of degradation products using liquid chromatography-mass spectroscopy
      (LC-MS) demonstrated that all poly(ester amine)s had a hyperbranched structure
      with a degree of branching of approximately 0.30. These poly(ester amine)s were
      readily water-soluble and degradable under physiological conditions (pH 7.4, 37
      degrees C), in which more than 10% ester bonds were hydrolyzed within 4 h.
      Moreover, these hyperbranched poly(ester amine)s showed high buffering capacities
      between pH 5.1 and 7.4. Three out of nine synthesized polymers, i.e. p(HDDA-AEP),
      p(HDDA-AMP), and p(BDDA-AMP), were shown to effectively condense plasmid DNA into
      small-sized (approximately 94-135 nm) and positively charged complexes.
      Polymer/DNA complexes ('polyplexes') based on these three polymers, and larger
      complexes of p(BDDA-AEP) (approximately 497 nm) were able to transfect COS-7
      cells in vitro. Importantly, the transfection activity of polyplexes was
      preserved in the presence of serum proteins. The highest transfection level was
      observed for p(HDDA-AEP) polyplex which had a transfection efficiency higher than
      or comparable to that polyplexes of polyethylenimine (PEI) and poly(2
      (dimethylamino)ethyl methacrylate) (pDMAEMA). Furthermore, these poly(ester
      amine)s revealed no or low cytotoxicity. These results demonstrated that
      hyperbranched poly(ester amine)s can be applied as safe and efficient gene
      delivery polymers.

PMID- 16081185
TI  - Priority setting for horizon scanning of new health technologies in Denmark:
      views of health care stakeholders and health economists.
AB  - In the context of the establishment of a Danish Horizon Scanning System (HSS) the
      views of health care stakeholders and health economists were solicited by means
      of postal surveys on the need for adaptation of a priority setting instrument for
      health technology assessment (HTA). The aim was to investigate if the instrument
      needed adaptation for priority setting in the context of a Danish HSS and, if so,
      how the instrument should be changed. A literature study served to enhance
      interpretation of the findings of the surveys and to formulate changes in the
      instrument that synthesize or bridge any differing views between the two groups.
      The results show that the instrument should apply a health care perspective, and
      that technologies should be prioritised on the basis of the criteria: marginal
      benefits, marginal costs, budget impact, impact on access to care, and additional
      criteria with an impact on health policy, such as the educational needs and
      organisational changes associated with the new technology. The proposed changes
      are regarded as an intermediate step in the process of producing a fully adapted
      instrument that can serve as a formal support for priority setting of new health
      technologies for assessment in the Danish HSS.

PMID- 16081186
TI  - Dendritic localization of the transcriptional co-repressor Groucho/TLE1 in
      cortical and cerebellar neurons.
AB  - In the present study we show that the transcription factor Groucho/TLE1 (TLE1) is
      expressed in virtually all major cortical subdivisions, hippocampus, amygdala,
      and thalamus, as well as in the cerebellum of the adult rat brain. In both
      neocortex and subcortical structures, TLE1 expression was mostly localized to
      neurons. In addition to the expected nuclear localization, TLE1 immunoreactivity
      was also detected in apical dendritic shafts of neocortical layer III and V
      pyramidal cells and in Purkinje cell dendrites. These results demonstrate that
      TLE1 expression occurs in the mature nervous system and suggest that this protein
      may perform new functions outside of the nucleus in selected cortical and
      cerebellar neurons.

PMID- 16081187
TI  - Neuronal and glial cell lines as model systems for studying P2Y receptor
      pharmacology.
AB  - Investigation of the role of extracellular nucleotides in nervous system has been
      one of the main topics of the P2Y receptor research throughout the years. In
      parallel to numerous studies on primary culture systems, various neuronal and non
      neuronal cell lines have been used to model in vitro the processes mediated by
      extracellular nucleotides. In this review article, a survey of expression
      profiles of G protein-coupled P2Y receptor subtypes in nervous-system-derived
      cell lines is presented, by analysing the receptor expression at the mRNA,
      protein, and functional level. The variability of receptor expression profiles in
      established cell lines is further discussed, bringing forward some general
      properties for neuronal and glial malignant cell lines.

PMID- 16081188
TI  - Relearning how to learn: enrolled nurse transition to degree at a New Zealand
      rural satellite campus.
AB  - The demise of enrolled nurse (EN) training in New Zealand hastened the
      development of transition to registration/degree programmes for enrolled nurses.
      A North Island tertiary institution developed a flexible course to enabled ten
      enrolled nurses working in rural settings, the majority of whom were Maori, to
      continue working while studying at a small satellite campus. An exploratory,
      descriptive, qualitative research study utilizing focus group interviews was
      undertaken to examine the factors that assisted or hindered their transition. Two
      major categories emerged from comparative analysis of the data. One category
      entitled 'relearning how to learn', demonstrated the cognitive and behavioural
      adaptations made and is the focus of this paper. The other category 'barriers and
      catapults', demonstrated the physical and environmental factors that influenced
      the students' transition but is outside the scope of this paper. Recent changes
      in New Zealand nursing education have witnessed the clarification of scopes of
      nursing practice and the controversial development of a new Certificate in Health
      Science (Nurse Assistant). Currently enrolled nurses are again facing threats to
      employment and it is envisaged that many will be seeking to undertake transition
      to registered nurse in the near future.

PMID- 16081189
TI  - TLR agonists as vaccine adjuvants: comparison of CpG ODN and Resiquimod (R-848).
AB  - TLR ligands that mimic pathogen associated molecular patterns and activate immune
      cells via Toll-like receptors (TLRs) are being developed for use in humans as
      therapy against a variety of diseases as well as vaccine adjuvants. These include
      imidazoquinoline compounds such as Imiquimod and Resiquimod (R-848) that bind to
      TLR7 and 8, as well as CpG oligodeoxynucleotides (CpG ODN) that bind to TLR9.
      This study was aimed at comparing CpG ODN and R-848 for their potential use as
      vaccine adjuvants and to determine whether there are additive or synergistic
      effects when they are used together. Using HBsAg as a model antigen in mice, we
      show CpG ODN to be superior to R-848 for augmenting both humoral and cell
      mediated immune responses.

PMID- 16081190
TI  - Comment on B. Zinka et al., Unexplained cases of sudden infant death shortly
      after hexavalent vaccination.

PMID- 16081191
TI  - Uranium in sediments, mussels (Mytilus sp.) and seawater of the Krka river
      estuary.
AB  - The response of an aquatic environment to the decrease of phosphate discharges
      from a technologically improved transhipment terminal, situated at the Croatian
      Adriatic coast in the port of Sibenik, has been assessed based on uranium
      activity and concentration in sediment, seawater and mussels Mytilus sp. The
      highest 238U activities (485+/-16Bqkg(-1) dry weight) were found in the sediment
      sample collected from the sampling site closest to the terminal. The maximum
      concentrations in the sediment samples are above the natural ranges and clearly
      indicate the harbour activities' influence. The 238U/226Ra activity ratios in
      sediment samples demonstrate the decreasing trend of phosphate ore input. Mussel
      samples showed levels of 238U activities in the range from 12.1+/-2.9 to 19.4+/
      7.2 Bqkg(-1) dry weight, thus being slightly higher than in normally consumed
      mussels. Only the seawater, taken just above the bottom sediment at the sampling
      site closest to the terminal, shows a slightly higher uranium concentration
      (3.1+/-0.2 microgL(-1)) when compared to the samples taken in upper seawater
      layers (2.1+/-0.2 microgL(-1)) but is in the range of the concentration level of
      uranium in natural seawater. Since the transhipment terminal in the port of
      Sibenik was modernised in 1988, discharge of phosphate ore into the seawater was
      drastically reduced and, consequently, uranium concentration levels in seawater
      have decreased. However, enhanced uranium activity levels are still found in
      deeper sediment layer samples and in mussel.

PMID- 16081192
TI  - Estimation of doses received in a dry-contaminated residential area in the
      Bryansk region, Russia, since the Chernobyl accident.
AB  - In nuclear preparedness, an essential requirement is the ability to adequately
      predict the likely consequences of a major accident situation. In this context it
      is very important to evaluate which contributions to dose are important, and
      which are not likely to have significance. As an example of this type of
      evaluation, a case study has been conducted to estimate the doses received over
      the first 17 years after the Chernobyl accident in a dry-contaminated residential
      area in the Bryansk region in Russia. Methodologies for estimation of doses
      received through nine different pathways, including contamination of streets,
      roofs, exterior walls, and landscape, are established, and best estimates are
      given for each of the dose contributions. Generally, contaminated soil areas were
      estimated to have given the highest dose contribution, but a number of other
      contributions to dose, e.g., from contaminated roofs and inhalation of
      contaminants during the passage of the contaminated plume, were of the same order
      of magnitude.

PMID- 16081193
TI  - Inorganic PM2.5 at a U.S. agricultural site.
AB  - In this study, we present approximately two years (January 1999-December 2000) of
      atmospheric NH3, NH4+, HCl, Cl-, HNO3, NO3-, SO2, and SO4= concentrations
      measured by the annular denuder/filter pack method at an agricultural site in
      eastern North Carolina. This site is influenced by high NH3 emissions from animal
      production and fertilizer use in the surrounding area and neighboring counties.
      The two-year mean NH3 concentration is 5.6 (+/-5.13) microg m(-3). The mean
      concentration of total inorganic PM2.5, which includes SO4=, NO3-, NH4+, and Cl-,
      is 8.0 (+/-5.84) microg m(-3). SO4=, NO3-, NH4+, and Cl- represent, respectively,
      53, 24, 22, and 1% of measured inorganic PM2.5. NH3 contributes 72% of total NH3
      + NH4+, on an average. Equilibrium modeling of the gas+aerosol NH3/H2SO4/HNO3
      system shows that inorganic PM2.5 is more sensitive to reductions in gas +
      aerosol concentrations of sulfate and nitrate relative to NH3.

PMID- 16081194
TI  - Attention-deficit/hyperactivity disorder: an overview of the etiology and a
      review of the literature relating to the correlates and lifecourse outcomes for
      men and women.
AB  - This paper provides a summary of the current conceptualization of what AD/HD is,
      and its etiology, and then reviews some of the recent literature on the
      correlates and lifecourse outcomes for individuals diagnosed with Attention
      Deficit/Hyperactivity Disorder (AD/HD). The intention is to synthesize that which
      is known, and to identify important gaps in the literature and knowledge base,
      which secondary analysis of prospective large-scale longitudinal cohorts,
      tracking individuals from birth to adulthood, could help to fill. This review
      highlights the fact that such datasets are rare and that their analysis offers
      important opportunities for advancing knowledge, particularly of the adult
      outcomes of childhood AD/HD.

PMID- 16081195
TI  - Low linking social capital as a predictor of coronary heart disease in Sweden: a
      cohort study of 2.8 million people.
AB  - This study investigated the association between the recently minted concept of
      linking social capital and incidence of coronary heart disease (CHD). A follow-up
      study of 1,358,932 men and 1,446,747 women in Sweden aged 45-74 years was
      conducted between 1 January 1998 and 31 December 1999. Neighbourhood linking
      social capital was conceptualised as proportions of individuals voting in local
      government elections at neighbourhood level. The neighbourhood- and individual
      level factors were analysed within a multilevel framework. Linking social capital
      was associated with CHD in both men and women beyond individual-level factors: in
      neighbourhoods with low linking social capital the odds ratios were 1.19 (CI =
      1.14-1.24) and 1.29 (CI = 1.21-1.38) for men and women, respectively, after
      adjustment for age, country of birth, education, marital status, and housing
      tenure. The significant between-neighbourhood variance (i.e. the random
      intercept) showed significant differences in CHD incidence between
      neighbourhoods. Even in a relatively egalitarian society, as exemplified by the
      Swedish Welfare State, individual health is affected by differences between
      neighbourhoods in linking social capital. The use of linking social capital
      represents a novel conceptual advance in research on the association between CHD,
      one of the major causes of death in Western countries, and the multidimensional
      aspects of social capital.

PMID- 16081196
TI  - Psychosocial stress and social support as mediators of relationships between
      income, length of residence and depressive symptoms among African American women
      on Detroit's eastside.
AB  - Patterns of mental health are clearly associated with life circumstances,
      including educational and economic opportunities, access to safe and supportive
      neighborhoods, socially structured exposures to stressors and to supportive
      relationships. In this article, we examine the social and economic correlates of
      depressive symptoms among African American women residing within a predominantly
      African American urban neighborhood in Detroit, USA, with relatively few economic
      resources. We identify distinct stressors associated with financial strain,
      neighborhood social disorder (concern about police responsiveness, safety
      stress), and experiences of discrimination. We test the extent to which each of
      these stressors mediates relationships between household income, length of
      residence in the neighborhood, social support and depressive symptoms. Our
      results suggest that for women in this racially segregated area with a high
      concentration of poverty, relationships between household income and symptoms of
      depression are partially mediated by financial stress and social support, but
      that stressors associated with neighborhood disorder and discrimination influence
      depressive symptoms independent of household income. Furthermore, we find that
      length of residence in the neighborhood is negatively associated with financial
      stress and positively associated with police stress and social support, with no
      significant net effect on symptoms of depression. We conclude that higher
      household income may help reduce symptoms of depression by reducing financial
      stress and strengthening social support even within neighborhoods with high
      concentrations of poverty. However, increased household income does not protect
      African American women residing in a high poverty community from distress
      associated with neighborhood disorder or experiences of discrimination.

PMID- 16081197
TI  - Effects of aminopentol on in utero development in rats.
AB  - Aminopentol (AP1), the backbone and main hydrolysis product of the mycotoxin
      fumonisin B1 (FB1), is present in corn-based foods which are consumed daily as a
      substantial part of the diet in some areas of the world. The toxicity of FB1 has
      been attributed to altered sphingolipid metabolism, but the toxicity of AP1 is
      less certain. Epidemiological correlations and in vitro studies have suggested
      that AP1 can increase neural tube defects (NTDs), but no in vivo developmental
      study of AP1 was done prior to this study. AP1 was given once daily to rats by
      gavage on gestation days (GD) 3-16 at doses of 0, 15, 30, 60, or 120 mg/kg.
      Reproductive and developmental parameters were measured at GD 17, one day after
      the last dose, and on GD 20. In addition, on GD 17, maternal and fetal tissues
      were analyzed for sphingolipid content. CONCLUSIONS: AP1 reduced dam body weight
      gain, but was less toxic than FB1. AP1 was not teratogenic, did not affect tissue
      sphingolipid ratios, did not alter reproduction or development of fetuses, and
      produced no dose-related histopathological effects in dams.

PMID- 16081198
TI  - Effect of reduced glutathione treatment on selenosis, blood selenium
      concentration and glutathione peroxidase activity after repeated short-term
      selenium exposure in buffalo calves.
AB  - Effects of repeated feeding of selenium, when given alone or along with reduced
      glutathione, on whole blood selenium levels, selenosis and glutathione peroxidase
      activity, was studied in buffalo calves. After feeding 2.5 mg/kg of BW sodium
      selenite, good correlation was found between the onset of selenosis and whole
      blood selenium concentrations. Adverse effects appeared when the whole blood
      selenium concentrations increased above 2 microg/ml and mortality occurred when
      they exceeded 3.4 microg/ml. Reduced glutathione, given i.v. at 5 mg/kg of BW
      arrested the progress of selenosis and prevented mortality which was 100% in the
      sodium selenite supplemented group; also a reduced whole blood selenium
      concentration was noted. Whole blood selenium concentrations were a better and
      more sensitive indicator of selenium status than glutathione peroxidase activity
      alone.

PMID- 16081199
TI  - Induction of mild hypothermia with infusion of cold (4 degrees C) fluid during
      ongoing experimental CPR.
AB  - INTRODUCTION: Therapeutic hypothermia after resuscitation has been shown to
      improve the outcome regarding neurological state and to reduce mortality. The
      earlier hypothermia therapy is induced probably the better. We studied the
      induction of hypothermia with a large volume of intravenous ice-cold fluid after
      cardiac arrest during ongoing cardiopulmonary resuscitation (CPR). METHODS:
      Twenty anaesthetised piglets were subjected to 8 min of ventricular fibrillation,
      followed by CPR. They were randomized into two groups. The hypothermic group was
      given an infusion of 4 degrees C acetated Ringer's solution 30 ml/kg at an
      infusion rate of 1.33 ml/kg/min, starting after 1 min of CPR. The control group
      received the same infusion at room temperature. All pigs received a bolus dose of
      vasopressin after 3 min of CPR. After 9 min, defibrillatory shocks were applied
      to achieve restoration of spontaneous circulation (ROSC). Core temperature and
      haemodynamic variables were measured at baseline and repeatedly until 180 min
      after ROSC. Cortical cerebral blood flow was measured, using Laser-Doppler
      flowmetry. RESULTS: All pigs had ROSC, except one animal in the hypothermic
      group. Only one animal in the hypothermic group died during the observation
      period. The calculated mean temperature reduction was 1.6+/-0.35 degrees C (S.D.)
      in the hypothermic group and 1.1+/-0.37 degrees C in the control group (p=0.009).
      There was no difference in cortical cerebral blood flow and haemodynamic
      variables. CONCLUSION: Inducing hypothermia with a cold infusion seems to be an
      effective method that can be started even during ongoing CPR. This method might
      warrant consideration for induction of early therapeutic hypothermia in cardiac
      arrest victims.

PMID- 16081200
TI  - A hemoglobin-based oxygen carrier, bovine polymerized hemoglobin (HBOC-201)
      versus hetastarch (HEX) in a moderate severity hemorrhagic shock swine model with
      delayed evacuation.
AB  - OBJECTIVE: To evaluate the efficacy of HBOC-201 for resuscitation of hemorrhagic
      shock in a swine model incorporating soft tissue injury and delayed evacuation.
      METHODS: A muscle crush injury and 40% estimated blood volume controlled
      hemorrhage was completed in 24 Yucatan mini-pigs. Pigs were untreated or
      resuscitated with HBOC-201 or 6% hetastarch (HEX) at 20 min. Invasive
      hemodynamics and clinical variables were monitored for 4 h (pre-hospital phase)
      and subsequent fluid infusions were administered for severe hypotension or
      tachycardia. Animals were recovered from anesthesia and monitored non-invasively
      to 72 h (hospital phase). RESULTS: 100% (8/8) of HBOC-201-, 88% (7/8) of HEX-,
      and 63% (5/8) of non-resuscitated pigs, survived to 72 h (p=0.27). Mean arterial
      pressure, mean pulmonary arterial pressure and systemic vascular resistance index
      were higher in HBOC-201 pigs. By 90 min, cardiac index was restored to baseline
      in the HBOC-201 group and was 1.4-fold greater than baseline in the HEX group.
      HBOC-201 pigs had lower fluid requirements than HEX pigs (18.8+/-1.8 and 29.9+/
      1.1 ml/kg, p<0.001) in the pre-hospital phase and required fewer blood
      transfusions (1.3+/-1.3 and 9.4+/-0.6 ml/kg, respectively, p<0.001) in the
      hospital phase. Urine output and blood creatinine were comparable in HBOC-201 and
      HEX pigs. Tissue oxygenation levels were highest in the HBOC-201 group.
      CONCLUSIONS: As HBOC-201 restored hemodynamics and tissue oxygenation and
      decreased fluid requirements, in comparison with HEX, HBOC-201 was at least as
      efficacious and possibly a superior resuscitative fluid in a military-relevant
      delayed evacuation hemorrhagic shock swine model.

PMID- 16081201
TI  - Factors influencing survival after in-hospital cardiopulmonary resuscitation.
AB  - INTRODUCTION: During recent years, in-hospital cardiopulmonary resuscitation
      (CPR) management has received much attention. However, the rate of survival after
      in-hospital resuscitation in Iran hospitals is not known. Therefore, a study was
      designed to evaluate the outcome of in-hospital cardiopulmonary resuscitation
      (CPR) in the city of Kashan, Iran, during a 6-month period during 2002. MATERIAL
      AND METHODS: A prospective descriptive study was conducted on all cases of in
      hospital cardiopulmonary resuscitation. Necessary data including the age and sex
      of patients, shift, time from cardiac arrest until initiating of CPR, time from
      cardiac arrest until defibrillation, duration and result of CPR, were recorded in
      a checklist. Descriptive statistics presented. RESULTS: A total of 206 cases of
      CPR were attempted during the research period. The study population consisted of
      59.2% males and 40.8% females. The survival rate was similar for both sexes.
      Short-term survival was observed in 19.9% of cases and only 5.3% survived to
      discharge. The key predictors of survival to hospital discharge were CPR
      duration, time of cardiac arrest, time from cardiac arrest to initiation of CPR,
      and defibrillation within the first few minutes of cardiac arrest. CONCLUSIONS:
      Our study showed that it needs more attention to be paid to cardiopulmonary
      resuscitation management in Iran's hospitals. The results of this study could be
      an important first step toward a national study on the survival after
      cardiopulmonary resuscitation to provide accurate data on our performance with
      regards to the chain of survival.

PMID- 16081202
TI  - A comparison of three neonatal resuscitation devices.
AB  - BACKGROUND: Ventilation during neonatal resuscitation involves the use of self
      inflating bags, flow-inflating bags, and T-piece resuscitators. The ability of
      operators to deliver desired peak inspiratory pressures (PIP), positive end
      expiratory pressures (PEEP), prolonged inflations and the length of time to
      transition between different pressures has not been compared for all three of
      these devices. OBJECTIVE: To compare the ability of neonatal resuscitation
      personnel to deliver predetermined ventilation interventions using these devices
      in advance of a clinical trial of neonatal resuscitation. DESIGN/METHODS: We
      studied 31 operators (neomatologists, neonatal respiratory therapists, neonatal
      fellows, a pediatrician, pediatric residents, neonatal nurse practitioners, and
      neonatal nurses) using a T-piece resuscitator (Neopuff), Fisher and Paykel
      Healthcare, Auckland, New Zealand), a self-inflating bag (Baby Blue II, Vital
      Signs, Totowa, NJ), and a flow-inflating bag (Model E191 Anesthesia Associates,
      San Marcos, CA). The self-inflating bag was tested with and without the
      manufacturer's PEEP valve. Using a continuous pressure recording system and a
      neonatal manikin, we evaluated the ability to deliver a consistent PIP of 20 or
      40 cmH2O and a PEEP of 5 cmH2O during 30 s of ventilation, the ability to
      maintain a 5 s inflation at a PIP of 20 cmH2O and the time to transition from a
      PIP of 20 to 40 cmH2O. Each device was evaluated with and without a qualitative
      CO2 detector (Pedicap) Nellcor Pleasanton, CA). RESULTS: The T-piece resuscitator
      delivered the desired PIP more precisely and consistently compared with the self
      inflating bag at a target of 20 cmH2O (maximum PIP 20.7 cmH2O, S.D.=0.8 versus
      24.7 cmH2O, S.D.=2.8; p<0.001). At a target of 40 cmH2O, the maximum pressure
      delivered with the T-piece resuscitator was significantly less than both the flow
      inflating bag and the self-inflating bag (39.7 cmH2O, S.D.=2.1 versus 44 cmH2O,
      S.D.=3.3 versus 45.3 cmH2O, S.D.=4.7; p<0.001). It took significantly longer to
      increase the PIP from 20 to 40 cmH2O using the T-piece resuscitator compared to
      the self-inflating bag or the flow-inflating bag (5.7 s versus 2.2 s versus 1.8
      s; p<0.001), and three operators could not make the transition in the allotted 15
      s time limit. During the 5 s prolonged inflation, the T-piece resuscitator and
      the flow-inflating bag maintained a pressure greater than 18 cmH2O for a longer
      time than the self-inflating bag (4 s versus 3.7 s versus 2.2 s; p<0.001). The
      self-inflating bag with the PEEP valve in place provided significantly less PEEP
      than both the T-piece resuscitator and the flow-inflating bag (3.6 cmH2O versus
      4.4 cmH2O versus 4.4 cmH2O; p<0.005). The Pedicap did not significantly affect
      any of the observed results, and there were no consistent operator differences
      between different disciplines or years of experience. CONCLUSIONS: The T-piece
      resuscitator delivered the desired pressures more accurately, but required
      greater time to increase the PIP from 20 to 40 cmH2O. It was difficult to
      maintain a prolonged inflation and deliver the desired PEEP with the self
      inflating bag even with the PEEP valve in place. There is a need for improvement
      in the design and function of current manual resuscitation devices and for
      prospective trials to evaluate the optimal method of bag and mask ventilation
      during resuscitation of the newborn infant.

PMID- 16081203
TI  - Microglia and inflammation-mediated neurodegeneration: multiple triggers with a
      common mechanism.
AB  - Inflammation, a common denominator among the diverse list of neurodegenerative
      diseases, has recently been implicated as a critical mechanism responsible for
      the progressive nature of neurodegeneration. Microglia are the resident innate
      immune cells in the central nervous system and produce a barrage of factors (IL
      1, TNFalpha, NO, PGE2, superoxide) that are toxic to neurons. Evidence supports
      that the unregulated activation of microglia in response to environmental toxins,
      endogenous proteins, and neuronal death results in the production of toxic
      factors that propagate neuronal injury. In the following review, we discuss the
      common thread of microglial activation across numerous neurodegenerative
      diseases, define current perceptions of how microglia are damaging neurons, and
      explain how the microglial response to neuronal damage results in a self
      propelling cycle of neuron death.

PMID- 16081204
TI  - Dechlorination of hexachlorobenzene using ultrafine Ca-Fe composite oxides.
AB  - Ca-Fe composite oxides with different Ca/Fe atomic ratios were synthesized by co
      precipitation method and characterized by X-ray diffraction (XRD), scanning
      electron microscopy with elemental X-ray analysis (SEM-EDX) and inductively
      coupled plasma optical emission spectrometer (ICP-OES). Their dechlorination
      activities were evaluated using hexachlorobenzene (HCB) as a model compound. The
      results indicate that the dechlorination activity is related to the composition
      of metal oxides. Different compositions lead to the formation of different phases
      of Ca-Fe composite oxides. When Ca/Fe atomic ratio was 3.4, the dechlorination
      activity reached 97%, which was the highest in the dechlorination of HCB at 300
      degrees C for 0.5 h. This may be related to the formation of Ca(2)Fe(2)O(5) phase
      and small agglomerate size of oxide crystal of about 1 microm. The effect of
      reaction time on HCB dechlorination and the pathway of dechlorination were
      investigated using the Ca-Fe composite oxide with the highest activity. It was
      found that hydrodechlorination took place in the destruction of HCB, the
      dechlorination efficiency is almost 100% after 2 h reaction. After reaction,
      quantitative measurement of chloride ion and qualitative analysis of CaCO(3)
      indicate besides hydrodechlorination, other degradation routes may be present.
      The mechanism of synergic dechlorination using Ca-Fe composite oxides was
      discussed.

PMID- 16081205
TI  - Removal of Cd and Zn from inorganic industrial waste leachate by ion exchange.
AB  - This paper presents a study of the removal of Cd and Zn present in the leachate
      from an inorganic industrial waste landfill using cationic exchange resins
      (Amberlite 200, 252-C, IR-120, Duolite C-464), a chelating resin, Amberlite IRC
      718, and an adsorbent resin, XAD-2. The chelating resin Amberlite IRC 718
      presented the higher removal in batch experiments for both metals (93% for Zn and
      50% for Cd). Five hundred ten bed volumes of leachate were treated in column
      experiments using this material, reducing the concentrations of Cd and Zn from 18
      mg/dm3 to 0.1 and 1.0mg/dm3, respectively. Regeneration of the saturated bed was
      achieved with 11 BV of 2M HCl.

PMID- 16081206
TI  - Degradation of chemical substances using wet peroxide oxidation under mild
      conditions.
AB  - The objectives of this study are to clarify the degradation mechanism of chemical
      substances using wet peroxide oxidation (WPO) under mild condition (150 degrees
      C) and to confirm the removal of polychlorinated biphenyls (PCBs) in soil using
      this oxidation process. Acetic and oxalic acids were mineralized using WPO. TOC
      removal rate of acetic acid was highest in the solution of pH 2.5. However, TOC
      removal rate was decreased with the increase in pH and TOC were hardly removed in
      the solution of pH 7 and 10. The decomposition rate of isobutyric acid by WPO
      decreased in the presence of radical scavenger (t-BuOH). The results suggested
      that the decomposition of chemical substances using WPO proceeded by hydroxyl
      radical (OH radical). PCBs in soil were also decomposed by performing WPO at 150
      degrees C.

PMID- 16081207
TI  - The partitioning of heavy metals in incineration of sludges and waste in a
      bubbling fluidized bed 2. Interpretation of results with a conceptual model.
AB  - This work addresses the behavior, fate and/or partitioning of six targeted (Cd,
      Pb, Cr, Cu, Zn and Ni) heavy metals (HMs) in the incineration of sludges and
      waste in a bubbling fluidized bed (BFB) of 15 cm i.d. and 5.2m high followed by a
      filter chamber operated at 750-760 degrees C with a commercial ceramic filter.
      This paper presents three different things: (1) an in depth review of the
      published work relating to the problem of partitioning of the HMs in BFBs, (2)
      some more experimental incineration tests regarding the influence of the
      temperature of the bed of the BFB and the effect of the chlorine content in the
      feedstock on the partitioning of the HMs, and (3) the modelling of the
      partitioning of the HMs in the exit flows: bottom ash, coarse fly ashes, fine fly
      ash and vapour phase. The partitioning of the HMs is governed by fluid dynamic
      principles together with the kinetics of the diffusion of the HMs inside the ash
      particles and the kinetics of the reactions between the HMs and the components of
      the matrix of the ash. Some thermodynamic predictions do not fit the results from
      the BFB incinerator well enough because equilibria are not reached in at least
      three exit ash flows: coarse fly ash, fine fly ash and submicron particles. The
      residence time of these ash particles in these type of incinerators is very short
      and most of the HMs have no time to diffuse out of the ash particle. Finally, an
      examination was made on how in the ceramic hot filter the partition coefficients
      for the HMs increased, mainly for Cd and Pb, when the Cl-content in the feedstock
      was increased.

PMID- 16081208
TI  - Adsorptions of high concentration malachite green by two activated carbons having
      different porous structures.
AB  - The adsorption of malachite green (MG) from aqueous solution by two different
      adsorbents (CZn5, PETNa8) were studied. Adsorbents were prepared from pine
      sawdust and polyethyleneterephatalate (PET) by chemical activation with ZnCl(2)
      and NaOH, respectively. The adsorption was carried out in a batch system as a
      function of dye concentration, pH and contact time. Both adsorbents were found to
      be very effective in removing the dye at high concentration with adsorption
      percentage in the order of CZn5 > PETNa8. The pH of dye solution in the range of
      6-10, was found favorable for the removal of malachite green by using the two
      adsorbents at high concentrations. Equilibrium times were 120 and 90 min for CZN5
      and PETNa8, respectively. Kinetics of removal MG was studied using Lagergren
      equation and diffusion phenomena was analyzed using Weber and Morris
      intraparticle diffusion plots. It was also showed that the adsorption isotherm
      followed Langmuir model.

PMID- 16081209
TI  - Continuous extraction and destruction of chloro-organics in wastewater using
      ozone-loaded Volasiltrade mark245 solvent.
AB  - Extracting waterborne contaminants to ozone-loaded Volasiltrade mark245 (a
      siloxane solvent in which ozone is ten times more soluble than water) has been
      studied as a means of enhancing reaction kinetics and thus, providing more rapid
      wastewater decontamination. Investigation was carried out with respect to 2
      chlorophenol and dichloromethane. Using a pilot scale continuous flow liquid
      liquid/ozone water treatment system, 2-chlorophenol was extracted to the ozone
      loaded solvent phase and considerable extents of destruction were achieved.
      However, the approach was demonstrated to yield slightly less destruction than
      direct gas contact for the same utilization of ozone and enhanced reaction
      kinetics were not shown to occur. This was suggested to be due to increased
      interfacial mass transfer resistance and/or the promotion of less destructive
      reaction pathways. Modification of the existing pilot system, by conversion from
      co- to counter-current solvent-loading, enabled greater dissolved ozone
      concentrations to be achieved within the solvent. Increasing the counter-current
      exchange column height to approximately 2.5m was suggested for achieving a near
      optimum level of performance. The liquid-liquid/ozone approach was demonstrated
      to be an effective means of indirectly exposing wastewater contaminants to
      concentrated ozone. As such the technology may be applicable as an alternative to
      direct gas contact in instances where the avoidance of contaminant sparging is
      desired (i.e. where contaminants are highly volatile, pungent and/or toxic) or
      foaming occurs.

PMID- 16081210
TI  - Chemical reduction of an unbuffered nitrate solution using catalyzed and
      uncatalyzed nanoscale iron particles.
AB  - Uncatalyzed and catalyzed nanoscale Fe(0) systems were employed for the
      denitrification of unbuffered 40 mgN L(-1) nitrate solutions at initial neutral
      pH. Compared to microscale Fe(0) (<100 mesh), the efficiency and rate of nitrate
      removal using uncatalyzed and catalyzed nano-Fe(0) were highly promoted, in which
      the maximum promoted rate was obtained using copper-catalyzed nano-Fe(0) (nano
      Cu/Fe). Nitrate first-order degradation rate constants (k(obs)) decreased
      significantly (>70%) with aged nano-Fe(0) and aged nano-Cu/Fe, and were recovered
      with NaBH(4) as reductants at levels of about 85 and 75%, respectively.
      Activation energies (E(a)) of nitrate reduction over the temperature range of 10
      60 degrees C were 42.5 kJ mol(-1) for microscale Fe(0), 25.8 kJ mol(-1) for nano
      Fe(0) and 16.8 kJ mol(-1) for nano-Cu/Fe. Unlike microscale Fe(0), the kinetics
      of denitrification by nano-Fe(0) and nano-Cu/Fe began to show characteristics of
      mass transport in addition to chemical reaction control. Ammonium was the
      predominant end product in all the systems. However, as for nitrite, 40% of the
      degraded nitrate persisted in the nano-Cu/Fe system. Thus, relative to nano
      Cu/Fe, nano-Fe(0) is a potential reductant for denitrification of groundwater as
      far as toxic nitrite generation is concern.

PMID- 16081211
TI  - Dye adsorption on unburned carbon: kinetics and equilibrium.
AB  - Unburned carbon in fly ash is an important by-product from coal combustion. In
      this investigation, unburned carbon has been separated from fly ash and been
      employed as a low cost adsorbent for a basic dye adsorption (Rhodamine B) in
      aqueous solution. Adsorption isotherm and kinetics of adsorption have been
      investigated using batch experiments. It is found that dye adsorption capacity
      depends on initial concentration, pH of solution, and temperature. The adsorption
      isotherm can be described by Langmuir model and the adsorption capacity of
      Rhodamine B at 30, 40, and 50 degrees C can reach 9.7 x 10(-5), 1.14 x 10(-4),
      and 1.5 x 10(-4)mol g(-1), respectively. The pseudo first- and second-order
      kinetic models have been employed to fit the dynamic adsorption. It is found that
      the dynamic adsorption follows the pseudo second-order model. Thermodynamic
      calculations indicate that the adsorption is endothermic reaction with DeltaH
      degrees at 25 kJ mol(-1).

PMID- 16081212
TI  - The change of the neuron-glia differentiation rate in human neural precursor
      cells (HPCs) and Ad-BDNF-/-GDNF-infected HPCs following the administration of a
      neurotoxin.
AB  - Neurotrophic factors promote the survival of various neurons, including
      peripheral autonomic and sensory neurons, as well as central motor and dopamine
      neurons, and it is expected that they could function as therapeutic agents for
      neurodegenerative disease. We examined the changes in the neuron-glia
      differentiation rate in normal human neural precursor cells (HPCs), Ad-BDNF- and
      Ad-GDNF-infected HPCs following their treatment with 6-OHDA. We isolated the
      precursor cells from the human fetal midbrain. To investigate the expression of
      differentiated cell markers within neurons and glia after 6-OHDA-induced toxicity
      in HPCs, immunocytochemistry was performed. Our results showed that the treatment
      with 6-OHDA (100, 200, 300, 400 and 500 microM) for 24 h decreased the viability
      of the HPCs in vitro. Among the growth factors tested, BDNF and GDNF protected
      the HPCs against 6-OHDA-induced toxicity. Approximately, 5.8+/-2.2% and 0.5+/
      0.1% of the HPCs treated with 6-OHDA were positive for the neuron marker, MAP2,
      and the oligodendrocyte marker, GalC, respectively, while 13.8+/-3.2% and 1.1+/
      0.36% of the Ad-BDNF- or Ad-GDNF-infected HPCs treated with 6-OHDA stained
      positive for MAP2 and GalC, respectively. These results suggest that cocktail
      therapy using human precursor cells (HPCs) and certain neurotrophic factors
      (BDNF, GDNF) provide direct protection against 6-OHDA-induced toxicity and has an
      effect on the differentiation rate.

PMID- 16081214
TI  - Development of a shear force scanning near-field fluorescence microscope for
      biological applications.
AB  - In this paper, a shear force scanning near-field fluorescence microscope combined
      with a confocal laser microspectrofluorometer is described. The shear force
      detection is realized based on a bimorph cantilever, which provides a very
      sensitive, reliable, and easy to use method to control the probe-sample distance
      during scanning. With the system, high-quality shear force imaging of various
      samples has been carried out. Furthermore, simultaneous shear force and near
      field fluorescence imaging of biological cells has also been realized. As an
      example, we especially present the result on the distribution of P-glycoprotein
      in the plasma membrane of human small cell lung cancer cells, suggesting that the
      system would be a promising tool for biological applications.

PMID- 16081215
TI  - Comparison of intensity distributions in tomograms from BF TEM, ADF STEM, HAADF
      STEM, and calculated tilt series.
AB  - The three-dimensional (3D) morphology of a nanometer-sized object can be obtained
      using electron tomography. Variations in composition or density of the object
      cause variations in the reconstructed intensity. When imaging homogeneous
      objects, variations in reconstructed intensity are caused by the imaging
      technique, imaging conditions, and reconstruction. In this paper, we describe
      data acquisition, image processing, and 3D reconstruction to obtain and compare
      tomograms of magnetite crystals from bright field (BF) transmission electron
      microscopy (TEM), annular dark-field (ADF) scanning transmission electron
      microscopy (STEM), and high-angle annular dark field (HAADF) STEM tilt series. We
      use histograms, which plot the number of volume elements (voxels) at a given
      intensity vs. the intensity, to measure and quantitatively compare intensity
      distributions among different tomograms. In combination with numerical
      simulations, we determine the influence of maximum tilt angle, tilt increment,
      contrast changes with tilt (diffraction contrast), and the signal-to-noise ratio
      (SNR) as well as the choice of the reconstruction approach (weighted
      backprojection (WB) and sequential iterative reconstruction technique (SIRT)) on
      the histogram. We conclude that because ADF and HAADF STEM techniques are less
      affected by diffraction, and because they have a higher SNR than BF TEM, they are
      better suited for tomography of nanometer-sized crystals.

PMID- 16081219
TI  - Diagnosis of Hepatozoon spp. in Amblyomma ovale and its experimental transmission
      in domestic dogs in Brazil.
AB  - Transmission of Hepatozoon spp. to dogs was investigated using four species of
      ixodid ticks: Rhipicephalus sanguineus, Amblyomma aureolatum, Amblyomma ovale and
      Amblyomma cajennense. We collected completely or partially engorged adult ticks
      of these species from dogs that were naturally infested and positive for
      Hepatozoon spp. We selected some of these ixodids and inoculated them orally in
      four negative dogs. The other ticks were dissected and examined for oocysts. Of
      all dogs inoculated orally with R. sanguineus, A. aureolatum, A. cajennense and
      A. ovale, only the animal that received the macerate of A. ovale was positive;
      evidence (gametocytes in peripheral blood) of infection was found 63 days after
      inoculation. Among all dissected ticks, we found only two oocysts; these were
      similar to those of Hepatozoon canis, and both were recovered from a single A.
      ovale specimen. We inoculated sporozoites recovered from the oocysts
      intraperitoneally into a Hepatozoon spp. negative dog, and circulating
      gametocytes were detected 84 days later. Our study demonstrated that A. ovale can
      be a vector of Hepatozoon spp. in Brazil.

PMID- 16081220
TI  - New trends and clinical patterns of human trichinellosis in Russia at the
      beginning of the XXI century.
AB  - Official national statistics show a gradual decline in the incidence of
      trichinellosis in Russia from 971 cases in 1996 to 527 cases in 2002. Of the
      total 864 cases involved in 47 trichinellosis outbreaks during 1998--2002, only
      35.8% were due to infected pork compared to 80% in 1995--1996. Other important
      sources were wild animals, such as bear (Ursus arctos) (39.5%), badger (Meles
      meles) (10.6%), and dog meat (11.9%). Children composed 15.9% of all cases.
      Overall, 81.0% of pork-cases occurred in the European part of the country, and
      89.4% of bear-meat cases were from the Asian region where most of the badger and
      dog-meat cases also originated. The percent of clinically severe cases of disease
      derived from pork and from bear meat was 7.7% and 7.9%, respectively; the
      frequency of moderate cases from pork was significantly higher than from bear
      meat. Clinically severe cases from badger and dog meat were 1.1% and 1.9%,
      respectively, where the number of clinically moderate cases from badger meat was
      significantly larger than that from dog meat. A disturbing trend is the 52.3% of
      trichinellosis cases during 1998--2002 in Russia that were derived from wild
      animal meat, especially the clinically severe cases occurring among the
      aboriginal Siberian population. The contributing factors to the slow decline in
      trichinellosis incidence in Russia and to the increase in percentage of cases
      originating from wild animal meat are the distribution and consumption of
      veterinary-uncontrolled pork, poaching and distribution of wild animal meat, and
      the neglect of medical and civil regulations. These trends should be seriously
      evaluated by the institutions of health, education, and by the veterinary
      service.

PMID- 16081221
TI  - Effects of a single footshock followed by situational reminders on HPA axis and
      behaviour in the aversive context in male and female rats.
AB  - Gender is an important factor in the vulnerability to develop psychopathologies.
      At the biological level, stress-related pathologies such as depression or post
      traumatic stress disorder (PTSD) are associated with profound disturbances of the
      hypothalamo-pituitary-adrenal (HPA) axis. The aim of the present study was to
      assess sex-differences in the long-term effect of an intense stressful procedure
      on HPA function and behaviour in the aversive context in rats. Female and male
      rats experienced an aversive procedure consisting in an electric footshock (2mA,
      10s) in a dark chamber followed by 3 weekly situational reminders (SR, 2min in
      the white chamber close to the footshock chamber). Our results indicate that 41
      days after the end of the aversive procedure, female rats showed an increase of
      the corticosterone negative feedback in response to restraint stress, whereas
      such effect was not observed in males. Despite this change in the hormonal
      response, glucocorticoid receptors mRNA expression in the hippocampus was not
      affected in shocked females. In contrast, a significant increase of the
      mineralocorticoid receptors mRNA was observed in the CA2 of the hippocampus in
      shocked males. Finally, CRH mRNA levels in the paraventricular nucleus of the
      hypothalamus (PVN) were decreased in both female and male animals exposed to the
      aversive procedure. Behavioural observation revealed that shocked males and
      shocked females showed a high level of avoidance. However, the latency to visit
      the shock box was lower in females, which spent also more time in this area than
      males. In conclusion, our results suggest that gender might be a key factor
      impacting the direction of the effects induced by an intense stress.
      Interestingly, only females exhibited an increased negative feedback of the HPA
      axis response to stress, which could parallel endocrine changes of PTSD.

PMID- 16081222
TI  - The codon for the methionine at position 129 (M129) in the human prion protein
      provides an alternative initiation site for translation and renders individuals
      homozygous for M129 more susceptible to prion disease.
AB  - Single amino-acid substitutions in the prion protein have been found to lead to
      resistance or susceptibility to amyloid fibril formation. In humans, the presence
      of methionine at position 129 in the prion protein results in increased
      susceptibility to prion disease, while the presence of valine at that position
      appears to be protective. It is hypothesized that the codon for M129 is an
      alternative initiation site for translation, which results in a truncated
      molecule that is missing the first 128 amino acids, including the signal peptide.
      This N-terminal truncated form of the prion molecule will not be transported to
      the extracellular space and thus will accumulate in the cytosol where it is more
      susceptible to fibril formation and aggregation; this aggregation could hinder
      normal degradation processes and cause disease. The results of experimental
      studies on truncated prion molecules support this hypothesis. To test the
      hypothesis, a gene segment, which when transcribed would result in a prion
      molecule starting at methionine 129, could be introduced into a convenient
      experimental animal to see if there is increased incidence of prion disease. Or,
      fibrils from the brains of affected M129/M129 homozygous individuals could be
      isolated and the molecules in the fibrils analyzed to determine the identity of
      the N-terminal amino acid(s). We predict that those isolates will have a
      preponderance of molecules that start with the methionine at position 129 in the
      intact protein.

PMID- 16081223
TI  - Colorectal cancer among Asians and Pacific Islanders in the U.S.: survival
      disadvantage for the foreign-born.
AB  - BACKGROUND: Asian Americans and Pacific Islanders (AAPI) have better colorectal
      cancer survival than other racial populations. However, immigrants face
      challenges that may place them at higher risk for late diagnosis and death.
      METHODS: To compare survival between the foreign- and U.S.-born, we identified
      17,302 AAPI colorectal cancer patients between 1973 and 1998 from the
      Surveillance, Epidemiology, and End-Results (SEER) Program. Patients were
      categorized as foreign-born or U.S.-born using multiple imputation methods.
      RESULTS: Foreign birth was associated with higher risk for death from any cause
      (hazard ratio [HR] 1.29; 95% CI 1.23-1.36) and with modestly higher risk after
      adjustment for selected demographic characteristics (HR 1.13; 95% CI 1.05-1.21)
      and registry site (HR 1.05; 95% CI 0.98-1.14). Although foreign-born AAPI were
      more likely to present later, additional adjustment for cancer stage reduced but
      did not eliminate their higher risk of death (HR 1.09; 95% CI 1.01-1.18)
      CONCLUSIONS: Compared to the U.S.-born, foreign-born AAPI have poorer survival
      following colorectal cancer diagnosis. Future investigation of the care processes
      after diagnosis may be important in understanding these differences.

PMID- 16081224
TI  - [Use of 16S rRNA gene sequencing for identification of "Pseudomonas-like"
      isolates from sputum of patients with cystic fibrosis].
AB  - Since nonfermenting, Gram negative bacilli recovered from patients with cystic
      fibrosis could be misidentified with phenotypic procedures, we used partial 16S
      ribosomal RNA gene (16S gene) sequencing to identify these "Pseudomonas-like"
      isolates. 473 isolates were recovered from 66 patients in 2003. Sequencing was
      used to identify 29 (from 24 patients) of the 473 isolates, showing unclear
      results with routine tests. PCR with specific primers was carried out to amplify
      a 995 bp fragment, which was then sequenced. The sequences were analyzed with
      GenBank database for species assignment. Phenotypic and genotypic results were
      concordant for 20/29 isolates (10 Pseudomonas aeruginosa, 5 Burkholderia cepacia,
      3 Stenotrophomonas maltophilia, 2 Achromobacter xylosoxidans). However, 3 of the
      5 B. cepacia isolates were then identified as Burkholderia multivorans with a PCR
      RFLP procedure. Phenotypic misidentification was observed for 9/29 isolates: 4 A.
      xylosoxidans, 1 P. aeruginosa, 1 Bordetella petrii, 1 Bordetella bronchiseptica,
      1 Ralstonia respiraculi and 1 Ralstonia mannitolilytica. Partial 16S gene
      sequencing improved the identification of "Pseudomonas-like" isolates from cystic
      fibrosis patients, but the accuracy to distinguish between genomovars of the B.
      cepacia complex was inadequate.

PMID- 16081225
TI  - [Retrospective study of Lyme borreliosis positive serologies in 2003].
AB  - PURPOSES OF THE STUDY: To estimate the percentage of positive sera for Lyme
      borreliosis antibodies, to precise the characteristics of clinical cases
      diagnosed from serological data and to determine their geographical distribution
      in France. MATERIALS AND METHODS: Studied sera were those received by the Pasteur
      Cerba laboratory in 2003. IgG and IgM isotypes were detected using the Dade
      Behring kits. Antibody specificity was analysed with the Meridian's western blot.
      RESULTS: 1504/16 176 (9%) sera were positive for IgG isotype, and 978/3298 (29%)
      for IgM. The specificity was confirmed by western blot in 49% cases for IgG and
      in 54% for IgM. The highest positive serology rates were found in eastern and
      centre regions and in Aquitaine. Forty-two cases have been investigated leading
      to the identification of 16 borreliosis cases, each suffering of an erythema
      migrans. Five of them had neurological signs. Patient mean age was 40 years. 87%
      of patients had risk factors and 69% reported previous tick bites, mainly on
      lower limbs. CONCLUSION: A low rate of positive borreliosis sera was found,
      suggesting that serology prescription should be limited to patients suffering of
      compatible clinical signs, as recommended by the EUCALB. Erythema migrans was the
      most frequent clinical manifestation and neurological signs were present in 30%
      of cases. Finally, the geographical case distribution was similar to that
      provided by the study of the Sentinelle network in 1999-2000.

PMID- 16081226
TI  - [Granulysin: antimicrobial molecule of innate and acquired immunity in human
      tuberculosis].
AB  - The recent global increase in cases of tuberculosis and the emergence of
      multidrug-resistant strains of tuberculosis have focused attention on the
      molecular mechanisms of human antimycobacterial immunity. The macrophage is not
      only the primary site for Mycobacterium tuberculosis growth but also ordinarily
      provides the primary lines of host defense against invading pathogens in its role
      as an effector of innate immunity. The ability of M. tuberculosis to survive and
      replicate in the host macrophage is critical to its pathogenesis, emphasizing a
      need for a clearer understanding of its interactions with the host macrophage.
      Macrophages use varied strategies to kill and destroy invading organisms,
      including production of reactive nitrogen and oxygen intermediates, phagosome
      maturation and acidification, fusion with lysosomes, exposure to defensins and
      host cell apoptosis. In human, granulysin is a recently identified antimicrobial
      protein expressed on cytotoxic T cells, natural killer (NK) cells and NKT cells.
      It has been shown that granulysin contributes to the defense mechanisms against
      mycobacterial infection. We hypothesized that human macrophages may possess
      antimicrobial substances, such as granulysin, and play a role in the defense
      mechanism.

PMID- 16081227
TI  - Early developmental origins of impaired lung structure and function.
AB  - Epidemiological studies show that exposure to factors that restrict fetal growth
      or lead to low birthweight can alter lung development and have later adverse
      effects on lung function and respiratory health. The major causal factors include
      reduced nutrient and oxygen availability, nicotine exposure via maternal tobacco
      smoking and preterm birth, each of which can affect critical stages of lung
      development. Experimental studies show that these environmental insults can
      permanently alter lung structure and hence lung function, increasing the risk of
      respiratory illness and accelerating the rate of lung aging. Further studies are
      required that address the molecular and cellular mechanisms by which these
      factors adversely affect lung development and whether such effects can be blocked
      or reversed. Ultimately however, a major goal should be to prevent prenatal
      compromises through clinical monitoring, and in the case of smoking through
      education, thereby ensuring that each fetus has the best possible environment in
      which to develop.

PMID- 16081228
TI  - Fetal programming of body composition and musculoskeletal development.
AB  - The prevalence of obesity, sarcopenia and osteoporosis is rising and there is
      increasing interest in determinants operating in early life. Fetal programming is
      the phenomenon whereby alterations in fetal growth and development in response to
      the prenatal environment have long term or permanent effects. Evidence for fetal
      programming of body composition and musculoskeletal development comes from
      epidemiological studies, investigation of the role of early undernutrition and
      preliminary findings on underlying mechanisms. Low birth weight and poor prenatal
      nutrition are associated with changes in adult body composition including altered
      fat distribution, reduced muscle mass and strength, and low bone mineral content.
      The mechanisms include a direct effect on cell number, altered stem cell function
      and resetting of regulatory hormonal axes. The next stage is translation of these
      findings into testable preventive strategies to maintain optimum body composition
      and minimize the risk of obesity, sarcopenia and osteoporosis in later life.

PMID- 16081229
TI  - Trunk anthropometry of Hong Kong Chinese infants.
AB  - BACKGROUND: Disturbed growth of the trunk may result in abnormal sternocostal
      relationship and a variety of pectus deformities. AIMS: The purposes of this
      study were to establish norms of trunk anthropometry for dysmorphology
      identification in the newborns and to evaluate chest circumference as a predictor
      for low birth weight for outborn infants where weighing scales were unavailable.
      STUDY DESIGN AND SUBJECTS: A total of 10,339 Chinese infants (5478 males, 4861
      females) with gestation 24-42 weeks from 12 hospitals were included. The
      anthropometric measurements analyzed included chest circumference, inter-nipple
      distance, sternal length and abdominal circumference. OUTCOME MEASURES: The LMS
      method using maximum penalized likelihood was used to perform model fitting of
      the anthropometric centiles for these physical parameters. RESULTS: References
      tables of the four physical parameters for newborns were constructed. Chest
      circumference showed the highest correlation with birth weight (male: r = 0.866,
      female: r = 0.883). The cut-off points for chest circumference of 295 (male) and
      299 mm (female) were the best predictor for low birth weight. There were also
      racial differences in these parameters. When compared with French infants,
      Chinese newborns had smaller chest circumference. CONCLUSION: These physical
      parameters provide useful references and aid dysmorphology diagnosis in newborns
      of ethnic Chinese origin.

PMID- 16081230
TI  - Factors affecting the plasma membrane function of cooled-stored stallion
      spermatozoa.
AB  - The spermatozoon is a highly specified cell that has the abilities of active
      motility and fertilization of the ovum. Damage to the sperm plasma membrane
      results in the irreversible loss of its functions. Because of the high content of
      unsaturated fatty acids in the plasma membrane, mammalian sperm are sensitive to
      oxidative stress. While mild peroxidation appears to promote capacitation of the
      sperm cell, excessive peroxidation will damage the plasma membrane and results in
      loss of motility and fertility. The functional integrity of the sperm plasma
      membrane can be determined by functional tests (determination of motility,
      resistance against hypoosmotic media) or different staining methods. Today,
      fluorescent dyes that allow the evaluation of membrane-intact cells are
      preferred. Computer-assisted evaluation or the use of flow cytometry has improved
      the precision of these methods. The use of cooled-shipped semen has become a
      routine method in the equine industry and semen stored at 5 degrees C for about
      24 h maintains fertility close to that of fresh semen. According to the
      suitability of their ejaculates for cooled-storage, stallions may be classified
      as "good coolers" or "poor coolers". Semen processing involves a number of
      factors that may damage the sperm plasma membrane. This includes addition of
      semen extender, centrifugation, cooling and storage at a temperature of 4-6
      degrees C. Extender media and their ingredients protect the sperm plasma membrane
      against environmental influences, but unsuitable composition of the extender can
      also promote membrane damage. Recent advantages in extender composition are based
      on the substitution of undefined factors such as milk or egg yolk by more defined
      and stable components.

PMID- 16081231
TI  - Antinociceptive activity of alcoholic extract of Hemidesmus indicus R.Br. in
      mice.
AB  - The ethanolic extract of roots of Hemidesmus indicus R.Br. (family:
      Asclepiadaceae) was investigated for possible antinociceptive effect in mice.
      Three models were used to study the effects of extracts on nociception, which was
      induced, by acetic acid (Writhing test), formalin (Paw licking test) and hot
      plate test in mice. Hemidesmus indicus R.Br. extract was administered in the dose
      range of 25, 50 and 100mg/kg orally 1h prior to pain induction. The preliminary
      phytochemical screening of the extract showed the presence of triterpenes,
      flavonoids, pregnane glycosides and steroids. Oral administration of Hemidesmus
      indicus extract revealed dose-dependent antinociceptive effect in all the models
      for antinociception and it blocked both the neurogenic and inflammatory pain and
      the nociceptive activity was comparable with the reference drug. The results
      indicate that alcoholic extract of Hemidesmus indicus R.Br. possesses a
      significant antinociceptive activity. The activity can be related with the
      significant phytochemicals such as triterpenes, flavonoids, and sterols reported
      in the root extract.

PMID- 16081232
TI  - Changes in hepatic drug metabolizing enzymes and lipid peroxidation by methanol
      extract and major compound of Orostachys japonicus.
AB  - The effects of methanol extract and gallic acid (3,4,5-trihydroxybenzoic acid) of
      Orostachys japonicus A. Berger on hepatic drug metabolizing enzymes and lipid
      peroxidation were investigated in rats treated with bromobenzene. The methanol
      extract of Orostachys japonicus reduced the activities of phase I enzymes,
      aminopyrine N-demethylase and aniline hydroxylase, that had been increased by
      i.p. injection of bromobenzene. Gallic acid isolated from Orostachys japonicus
      also reduced the aniline hydroxylase activity, while it did not affect the
      aminopyrine N-demethylase activity. The methanol extract and gallic acid restored
      the activity of epoxide hydrolase which had been decreased by bromobenzene.
      Hepatic glutathione content was lowered, along with increase in hepatic lipid
      peroxide, by bromobenzene administration. The hepatic lipid peroxidation induced
      by bromobenzene was prevented with the methanol extract and gallic acid of
      Orostachys japonicus. However, the decrease in glutathione was not altered by
      gallic acid. The present results suggest that the methanol extract and gallic
      acid of Orostachys japonicus may protect liver from bromobenzene toxicity
      through, at least in part, inhibiting the cytochrome P450-dependent monooxygenase
      activities and enhancing the activity of epoxide hydrolase. Antioxidant effect
      also may contribute to the protection of Orostachys japonicus against the
      bromobenzene-induced hepatotoxicity.

PMID- 16081233
TI  - Estimation of human body built in Egyptians.
AB  - Identification of an unknown body and prediction of growth from specific body
      measurements are very important tasks in the fields of physical anthropology and
      forensic medicine. Height and weight are two factors among others required to
      establish individuality of an unidentified body. In the present work, an attempt
      has been made to calculate the stature and weight from percutaneous tibial length
      and bimalleolar breadth. The study was carried out on 1000 living Egyptian
      individuals comprising 500 males and 500 females; their age was between 19 and 21
      years. A significant positive correlation between stature and tibial length in
      both sexes was recorded. The coefficient of determination showed that 56% of
      variation in stature was due to tibial length and bimalleolar breadth in males,
      while in females the coefficient of determination was 23%. On the other hand, the
      coefficient of determination for weight showed that 11% of variability in weight
      was due to tibial length and bimalleolar breadth in males, while in females it
      was 5%. Linear regression analysis was done for all variables in all cases. The
      regression equation formulae are helpful in the estimation of stature and weight
      of the deceased from tibial length and bimalleolar breadth when leg or foot is
      the only portion available for autopsy examination.

PMID- 16081234
TI  - LC-ESI-MSD fast determination of residual mitomycin C in hen aqueous humour after
      corneal refractive surgery.
AB  - A simple, fast and reliable method has been developed for the assay of traces of
      mitomycin C (MMC) in hen aqueous humour samples. The determination was carried
      out by high-performance liquid chromatography with electrospray ionization mass
      spectrometric detection. In isocratic elution analysis, the mobile phase was a
      mixture of water-acetonitrile (78:22, v/v) and the chromatographic column was
      C(18) at 35 degrees C. The method has been validated over a range from 0.1 to 250
      microg L(-1) in hen aqueous humour with correlation coefficients higher than
      0.999. Limit of detection and limit of quantification for MMC based in signal to
      noise ratio of 3 and 10, respectively, were 20 and 71 ng L(-1). The developed
      method allows the analysis of MMC in hen aqueous humour samples obtained at
      different times and conditions in order to evaluate and compare the efficacy of
      the drug administration.

PMID- 16081235
TI  - Recipients' perspective on breaking bad news: how you put it really makes a
      difference.
AB  - OBJECTIVE: The goal of this study was to show that physician communication style
      of breaking bad news affects how the physician is perceived, how satisfied
      recipients of bad news are with the consultation, and how they feel after the
      consultation. METHOD: Female participants (students, N=159) were asked to put
      themselves in the shoes of a patient receiving the bad news of a breast cancer
      diagnosis. Participants were randomly assigned to watch one of three prototypical
      physician communication styles of breaking bad news on videotape: patient-,
      disease-, or emotion-centered communication. RESULTS: Results showed that these
      three prototypical communication styles were perceived very differently and they
      determined how satisfied participants were with the consultation and how they
      felt after the consultation. Participants exposed to the patient-centered
      communication perceived the physician as most emotional, least dominant, most
      appropriate when it comes to conveying information, most available and most
      expressive of hope. Also, they reported to be most satisfied with the visit and
      they showed the least increase in negative emotions. CONCLUSION: A patient
      centered communication style has the most positive outcome for recipients of bad
      news on a cognitive, evaluative, and emotional level. PRACTICE IMPLICATIONS:
      Results of this study provide guidelines to physicians on how to convey bad news.

PMID- 16081236
TI  - Radiation induced MMP expression from rectal cancer is short lived but
      contributes to in vitro invasion.
AB  - AIMS: Matrix metalloproteinase (MMP) activity is increased after radiation. The
      aims of this study were to assess the time course of this increase and its
      effects on malignant cell invasion. METHODS: Colorectal cancer (HCT 116, LoVo, C
      170 HM 2, CaCO-2), fibroblast (46-BR.IGI, CCD-18 Co) and fibrosarcoma (HT1080)
      cell lines were irradiated at 4 gray (4 Gy) and matrix metalloproteinase gene and
      protein expression examined over a 96 h period by real time polymerase chain
      reaction and gelatin zymography. Invasion was assessed on Matrigel. Human rectal
      tumour MMP expression was compared before and after long course radiotherapy.
      RESULTS: Radiation increased MMP gene expression of tumour cell lines, and
      resulted in increased MMP protein activity in the HT1080 line. HT1080 and HCT 116
      in monoculture and LoVo in co-culture were more invasive after radiation at 48 h
      in vitro, but long course radiotherapy did not result in a consistent increase in
      MMP expression from human rectal tumour biopsies. CONCLUSIONS: Radiation results
      in increased MMP expression for a limited time period. This results in an early
      increase in cell line invasion. Further clinical research is required to clarify
      if MMP inhibition given perioperatively following radiotherapy decreases local
      recurrence rates.

PMID- 16081237
TI  - A review on the role of antioxidants in the management of diabetes and its
      complications.
AB  - Diabetes is a prevalent systemic disease affecting a significant proportion of
      the population worldwide. The effects of diabetes are devastating and well
      documented. There is increasing evidence that in certain pathologic states,
      especially chronic diseases, the increased production and/or ineffective
      scavenging of reactive oxygen species (ROS) may play a critical role. High
      reactivity of ROS determines chemical changes in virtually all cellular
      components, leading to lipid peroxidation. Production of ROS and disturbed
      capacity of antioxidant defense in diabetic subjects have been reported. It has
      been suggested that enhanced production of free radicals and oxidative stress is
      central event to the development of diabetic complications. This suggestion has
      been supported by demonstration of increased levels of indicators of oxidative
      stress in diabetic individuals suffering from complications. Therefore, it seems
      reasonable that antioxidants can play an important role in the improvement of
      diabetes. There are many reports on effects of antioxidants in the management of
      diabetes. In this paper, after complete bibliography and criticizing all relevant
      articles, the relationships between diabetes and oxidative stress and use of
      antioxidants in the management of diabetes and its complications have been well
      reviewed. This review well indicates that oxidative stress is involved in the
      pathogenesis of diabetes and its complications. Use of antioxidants reduces
      oxidative stress and alleviates diabetic complications.

PMID- 16081238
TI  - Alpha-tocopherol: roles in prevention and therapy of human disease.
AB  - Alpha-tocopherol, one of the eight isoforms of vitamin E, is the most potent fat
      soluble antioxidant known in nature. For years, it was thought that alpha
      tocopherol only functioned as a scavenger of lipid peroxyl radicals,
      specifically, oxidized low-density lipoprotein (oxLDL), thereby serving as a
      chief antioxidant for the prevention of atherosclerosis. In recent years, the
      many roles of alpha-tocopherol have been uncovered, and include not only
      antioxidant functions, but also pro-oxidant, cell signaling and gene regulatory
      functions. Decades of clinical and preclinical studies have broadened our
      understanding of the antioxidant vitamin E and its utility in a number of
      chronic, oxidative stress-induced pathologies. The results of these studies have
      shown promising, albeit mixed reviews on the efficacy of alpha-tocopherol in the
      prevention and treatment of heart disease, cancer and Alzheimer's disease. Future
      studies to uncover cellular and systemic mechanisms may help guide appropriate
      clinical treatment strategies using vitamin E across a diverse population of
      aging individuals.

PMID- 16081240
TI  - Hydrophilic polymers--biocompatibility testing in vitro.
AB  - Biocompatibility is one of the main prerequisites for safe use of medical
      devices. Estimation of cytotoxicity is a part of the initial evaluation laid down
      in ISO standards on biological evaluation of medical devices. Hydrophilic
      polymers (based on 2-hydroxyethyl methacrylate HEMA) doped by addition of
      selected additives with antioxidant and/or free radical scavenging potential
      (vitamin C and hindered amine stabilizer N-(2,2,6,6-tetramethylpiperidin-4
      yl)methacrylamide) were tested in different in vitro systems (3T3 Balb/c cell
      culture and a 3D human skin model) for biocompatibility and suitability for use
      as wound dressings. The results of the 3T3 NRU cytotoxicity test using both the
      direct and indirect contact approaches and a 3D skin model modified irritation
      test (EpiDerm) confirmed high biocompatibility and good skin tolerance of both
      the basic polymers and those enriched with specific additives up to a balanced
      level. HEMA polymer showed a beneficial effect against cytotoxicity of an
      irritant (sodium dodecyl sulfate). The in vitro biocompatibility test results
      were confirmed by human local skin tolerance testing.

PMID- 16081239
TI  - In vitro detection of differential and cell-specific hepatobiliary toxicity
      induced by geldanamycin and 17-allylaminogeldanamycin in rats.
AB  - The differential toxicity of two anticancer agents is described using the in
      vitro rat liver slice culture model. Liver slices from F-344 rats were cultured
      for 5 days in Waymouth's-based medium with exposure to a range of geldanamycin
      (GEL) or 17-allylaminogeldanamycin (17-AAG) concentrations. GEL induced
      concentration-dependent reduction of alkaline phosphatase and of gamma-glutamyl
      transferase levels, which are indicators of biliary epithelial cell(s) (BEC)
      viability, and exhibited hepatocellular toxicity at higher concentrations.
      Histologically, BEC cell injury was evident at the lowest GEL concentration (0.1
      microM) and progressed to overt bile duct necrosis at 5 microM, a level at which
      hepatocellular damage was also more prominent. Slices exposed to the same
      concentrations were more sensitive to toxic effects of GEL than of 17-AAG. 17-AAG
      at the lowest concentration had more slice biomarker retention than GEL, and
      histological analysis revealed minimal toxic effect on BEC. With increasing
      concentration, BEC were progressively lost, and BEC proliferation was completely
      inhibited at 5 microM 17-AAG. Hepatocellular injury was evident only at high dose
      exposures. This is believed to be the first use of an in vitro liver tissue model
      to accurately predict the differential and concentration-dependent toxicities of
      these compounds.

PMID- 16081241
TI  - The use of the fish cell lines RTG-2 and PLHC-1 to compare the toxic effects
      produced by microcystins LR and RR.
AB  - Cyanobacterial toxins, especially microcystins (MC), are found in eutrophied
      waters through the world. Acute poisonings of animals and humans has been
      reported following MC exposure. In the present study, two fish cell lines, PLHC-1
      and RTG-2, were evaluated after exposure to the cyanobacterial toxins MC-LR and
      MC-RR. The effects of different concentrations of the toxins were investigated in
      both cell lines at morphological and biochemical levels (total protein content,
      lactate dehydrogenase leakage, lysosomal activity and succinate dehydrogenase
      activity). The results obtained showed a decrease in protein content and no
      relevant increase in cell disruption, except for MC-LR in PLHC-1 cells.
      Morphological changes produced by microcystins were cellular swelling, blebbling,
      rounding, reduction in the cell number and increase in the number and size of
      lysosomal bodies. In addition, steatosis was produced in hepatoma PLHC-1 cells,
      particularly with MC-RR. Furthermore, the fish PLHC-1 cell line was more
      sensitive than RTG-2 cells to the cyanobacterial toxins compared, being the
      stimulation of the lysosomal function and the induction of steatosis the most
      specific changes detected.

PMID- 16081242
TI  - Toxicity of methoprene as assessed by the use of a model microorganism.
AB  - Methoprene is an insect juvenile growth hormone mimic, commonly used as a
      pesticide. Although widely used for the control of several pests, toxic effects
      on organisms of different phyla have been reported. These events triggered
      studies to clarify the mechanisms of toxicity of this insecticide putatively
      involved in ecological issues. Here we show the effect of methoprene on the
      normal cell growth and viability of a strain of the thermophilic eubacterium
      Bacillus stearothermophilus, previously used as a model for toxicological
      evaluation of other environment pollutants. Respiration studies were also carried
      out attempting to identify a putative target for the cytotoxic action of
      methoprene. Cell growth was affected and a decrease of the number of viable cells
      was observed as a result of the addition of methoprene to the growth medium, an
      effect reverted by the presence of Ca(2+). Methoprene also inhibited the redox
      flow of B. stearothermophilus protoplasts before the cytochrome oxidase segment,
      an effect further studied by individually assessing the enzymatic activities of
      the respiratory complexes. This study suggests that methoprene membrane
      interaction and perturbation of cell bioenergetics may underlie the mechanism of
      toxicity of this compound in non-target organisms.

PMID- 16081243
TI  - Cytotoxicity and induction of protective mechanisms in HepG2 cells exposed to
      cadmium.
AB  - Cadmium is a widespread industrial pollutant. The primary route of exposure
      occurs via contaminated drinking water or food supplies, and tobacco. Its chronic
      introduction and ingestion lead to bio-magnification in target organs, as the
      liver. The aim of this paper is to determine Cd cytotoxic concentrations in the
      human hepatoma cell line HepG2. Further aims are the study of the activation and
      involvement of protection mechanisms against Cd hepatotoxicity. Cd was
      accumulated within the cells, as measured by ICP-AES. Metallothioneins (MT-1 and 
      2), a family of metal-binding proteins, were induced in a dose-dependent way
      after treatment with concentrations below the IC(50) value (mean value 22
      microM). The over-expression of MT by Zn pre-treatment was able to defend against
      Cd cytotoxicity. Heat shock protein 70 kDa (hsp70) was induced at high non
      cytotoxic concentrations (5, 10 microM) probably as a consequence of
      proteotoxicity, but its over-expression by a sub-lethal heat shock was not able
      to protect the cells from Cd cytotoxic concentrations (20, 50, 100 microM).

PMID- 16081244
TI  - The use of flow cytometric methods in acute and long-term in vitro testing.
AB  - One principal demand for in vitro screening for toxic effects is the ease of
      performance and the high throughput of test methods. Flow cytometry offers the
      possibility to study several parameters simultaneously, e.g. cell cycle
      modulation, mode of cell death, activity of mitochondria. Aim of the present
      study was to assess the suitability of flow cytometry for the determination of
      cytotoxicity of test chemicals. Six chemicals chosen from the MEIC list
      (acetaminophen, isoniazid, paraquat, malathion, digoxin and 2,4-dichlorophenoxy
      acetic acid) were tested in HepG2, AAH-1, YAC-1 cells and human lymphocytes.
      Chemicals were applied for 24, 48 h or 28 days. The phases of the cell cycle were
      determined and the induction of apoptosis and necrosis was demonstrated by
      annexin binding, analysis of mitochondrial membrane potential and DNA strand
      breaks. The results of the present study show that flow cytometric methods are
      well suited to screen for the cytotoxicity of chemicals, both in adherent cells
      and cells grown in suspension.

PMID- 16081245
TI  - An isochore transition zone in the NF1 gene region is a conserved landmark of
      chromosome structure and function.
AB  - The mammalian genome is organized as a mosaic of isochores, stretches of DNA with
      a distinct sequence composition. Isochores form the basis of the chromosomal
      banding pattern, which is tightly correlated with a number of structural and
      functional features. We have recently demonstrated that the transition from a GC
      poor isochore to a GC-rich one in the NF1 gene region occurs within 5 kb and
      demarcates genomic regions with high and low recombination frequency. We now
      report that the same transition zone separates early replicating from late
      replicating chromatin on the molecular level. At the isochore transition the
      replication fork is stalled in mid-S phase and can be visualized by fiber-FISH
      techniques as a Y-shaped structure. The switch in GC content and in replication
      timing is conserved between human and mouse, emphasizing the importance of the
      transition zones as landmarks of chromosome organization and function.

PMID- 16081246
TI  - L3mbtl, the mouse orthologue of the imprinted L3MBTL, displays a complex pattern
      of alternative splicing and escapes genomic imprinting.
AB  - L3mbtl encodes a member of the Polycomb group of proteins, which function as
      transcriptional repressors in large protein complexes. The Drosophila D-l(3)mbt
      protein is considered a tumor suppressor since its inactivation results in brain
      tumors. The human L3MBTL gene lies in a region of chromosome 20 frequently
      deleted in patients with myeloid malignancies and has been proposed as a
      candidate 20q tumor suppressor gene. Recently we have shown that L3MBTL undergoes
      monoallelic methylation in hematopoietic tissues and is transcribed from the
      paternally derived allele. The mouse L3mbtl gene is located on chromosome 2, a
      region of syntenic homology with human chromosome 20, and in a region containing
      a number of genes subject to epigenetic regulation. Here we analyze the genomic
      structure and alternative splicing of L3mbtl and assess its imprinting status in
      mouse. L3mbtl displays a complex pattern of alternative splicing involving both
      5' noncoding and coding exons and is transcribed from two promoters. Unlike its
      human counterpart, L3mbtl escapes imprinting and there is no differential
      methylation of its CpG island.

PMID- 16081247
TI  - Reelin-immunoreactivity in the hippocampal formation of 9-month-old wildtype
      mouse: effects of APP/PS1 genotype and ovariectomy.
AB  - Reelin, an extracellular matrix protein has an important role in the migration,
      correct positioning and maturation of neurons during development. Though it is
      generally down-regulated in the postnatal period, expression of this large
      glycoprotein continues in the adult brain in some cell populations. In the
      present study, we examined the distribution of reelin-immunoreactivity (-ir) in
      the hippocampal formation of 9-month-old wildtype mice (WT). Then, reelin-ir in
      normal mice was compared to that of transgenic mice (APP/PS1) carrying mutated
      human APP and PS1 genes, which are linked to the familial form of Alzheimer's
      disease (AD). The APP/PS1 mice were additionally burdened with a second risk
      factor for AD, namely depletion of circulating gonadal hormones by ovariectomy
      (APP/PS1 + OVX). The analyses revealed that in adult WT reelin-ir is expressed by
      Cajal-Retzius cells and a subgroup of interneurons throughout the hippocampal
      formation. In addition, layer II projection neurons in the lateral entorhinal
      subfields are reelin-ir. Interestingly, ovariectomy decreases the number of
      reelin-ir cells in the hilus in WT mice, whereas AD-related genotype alone
      induces only a non-significant reduction. Unexpectedly, additional stress, e.g.,
      depletion of gonadal hormones, does not aggravate the slight reduction in the
      reelin cell number in the APP/PS1 mice. We propose that the changes in normal
      reelin-ir are linked to disturbances in repair mechanisms in which APP/PS1 and
      gonadal hormones are involved and which are perturbed in neurodegenerative
      conditions, namely AD.

PMID- 16081248
TI  - In vivo apoptosis induction and reduction of infectivity by an Autographa
      californica multiple nucleopolyhedrovirus p35(-) recombinant in hemocytes from
      the velvet bean caterpillar Anticarsia gemmatalis (Hubner) (Lepidoptera:
      Noctuidae).
AB  - Baculoviruses have long been shown to regulate apoptosis in cultured insect
      cells. Recently, this phenomenon was also reported to occur in vivo, reinforcing
      the importance of apoptosis in insect immunity against viruses. The vP35del
      virus, an Autographa californica multiple nucleopolyhedrovirus (AcMNPV)
      recombinant, was previously shown to induce apoptosis in Anticarsia gemmatalis
      cultured cells. In order to verify the AcMNPV interaction with hemocytes,
      apoptosis induction in vivo and its effects upon infectivity, we studied the
      course of intrahemocoelic infection of recombinant viruses (vHSGFP and
      vHSGFP/P35del) in A. gemmatalis larvae. Insect development and mortality were
      monitored and infection progress was followed by light, fluorescence and electron
      microscopy. For all doses tested, vHSGFP/P35del caused lower mortality than
      vHSGFP. Mortality of 95% occurred with a dose of 4x10(6) PFUs of vHSGFP, which
      was reduced to 60% for vHSGFP/P35del. GFP expression was first observed at 3 h
      p.i. for the two viruses, increasing for vHSGFP (40% at 120 h p.i.) and
      decreasing for vHSGFP/P35del (0% at 120 h p.i.). The virus vHSGFP/P35del induced
      apoptosis in hemocytes, with some budded virus being produced, and fragmented
      cells were observed between 24 and 72 h p.i. The recombinant vHSGFP induced
      typical wild-type cytopathic effects, with low production of occluded viruses
      until 120 h p.i. Plasmatocytes and granular hemocytes type 1 were the hemocytes
      most susceptible to both viruses. For these experimental conditions, we concluded
      that A. gemmatalis is a semi-permissive host to AcMNPV; moreover, apoptosis
      reduces AcMNPV infectivity and the p35 gene is essential for blocking apoptosis
      in this system.

PMID- 16081249
TI  - Nocardiopsis and Saccharothrix genera in Saharan soils in Algeria: isolation,
      biological activities and partial characterization of antibiotics.
AB  - Twenty-five soil samples were collected in the Algerian Sahara and analyzed to
      isolate rare actinomycetes. Eighty-six isolates with the same Nocardiopsis or
      Saccharothrix morphology were isolated on humic-vitamin B agar medium using
      dilution techniques and several antibiotics as selective agents. Certain of these
      antibiotics seemed to be very selective for some phenotypes. Morphological and
      chemotaxonomic characteristics led to identifying 54 isolates belonging to the
      Nocardiopsis genus and 32 isolates belonging to the Saccharothrix genus. An
      assessment of the antimicrobial properties of the isolates showed activities
      against Gram-positive bacteria, fungi and yeasts. Saccharothrix isolates
      possessed better antifungal activity than Nocardiopsis. One of them, labeled SA
      103, was therefore selected for identification of its antifungal antibiotic
      activities. Production of overall antifungal and antibacterial activities was
      checked on the complex medium ISP2 and a synthetic medium (SM) that contains
      glucose or starch as carbon source, and ammonium or nitrate as nitrogen source.
      The SM medium containing ammonium sulfate (0.2%), supplemented with starch (0.5%)
      and yeast extract (0.3%), was retained for production of antibiotics. Active
      substances were purified by a G25-80 Sephadex column and reverse phase HPLC. Two
      pure substances were obtained and named ZA01 and ZA02; they were characterized on
      the basis of combined data resulting from chemical tests, UV visibile and IR
      spectra and mass spectrometry. The two antibiotics were found to be related and
      were partially characterized as nucleotidic or nucleosidic antibiotics. Their
      structures consisted of a chain of three sugar units linked to an aromatic base
      containing a phosphate residue.

PMID- 16081250
TI  - The morphology of Saccharomyces cerevisiae colonies is affected by cell adhesion
      and the budding pattern.
AB  - Formation of organized colony morphology is clearly a result of organized,
      coordinated behavior of cells within a colony, which reflects changes in the cell
      environment, nutrient availability, inter- and intracolony signaling and others.
      Under standard conditions, colony morphology is specific to the particular yeast
      strain, which indicates that reproducibility of the structure appears to be a
      hallmark of programmed development. Our data indicate that markedly structured
      morphology of colonies formed by some haploid and diploid Saccharomyces
      cerevisiae strains is linked to formation of clusters of incompletely separated
      yeast cells organized into larger aggregates. A prerequisite to aggregate
      formation appears to be a monopolar budding pattern and the presence of an
      extracellular matrix and adhesins connecting individual clusters within
      aggregates. In contrast, less structured colonies of other strains are composed
      of non-aggregated cells exhibiting different modes of budding
      (axial/polar/random) in different colony areas. The budding pattern appears to be
      influenced more by the environment (the presence of surrounding cells, nutrient
      gradients, etc.) than by strain ploidy. Disruption of the BUD2 gene results in
      uniform random budding of cells and it partially influences colony morphology.

PMID- 16081251
TI  - Oxidative stress and pro-apoptotic conditions in a rodent model of Wilson's
      disease.
AB  - Wilson's disease (WD) is an inherited disorder, characterized by selective copper
      deposition in liver and brain, chronic hepatitis and extra-pyramidal signs. In
      this study, we investigated changes of biochemical markers of oxidative stress
      and apoptosis in liver, striatum and cerebral cortex homogenates from Long-Evans
      Cinnamon (LEC) rats, a mutant strain isolated from Long Evans (LE) rats, in whom
      spontaneous hepatitis develops shortly after birth. LEC and control (LE) rats at
      11 and 14 weeks of age were used. We determined tissue levels of glutathione
      (GSH/GSSG ratio), lipid peroxides, protein-thiols (P-SH), nitric oxide
      metabolites, activities of caspase-3 and total superoxide-dismutase (SOD),
      striatal levels of monoamines and serum levels of hepatic amino-transferases. We
      observed a decrease of protein-thiols, GSH/GSSG ratio and nitrogen species
      associated to increased lipid peroxidation in the liver and striatum - but not in
      the cerebral cortex - of LEC rats, accompanied by dramatic increase in serum
      amino-transferases and decrease of striatal catecholamines. Conversely, SOD and
      caspase-3 activity increased consistently only in the cortex of LEC rats. Hence,
      we assume that enhanced oxidative stress may play a central role in the cell
      degeneration in WD, at the main sites of copper deposition, with discrete pro
      apoptotic conditions developing in distal areas.

PMID- 16081252
TI  - Ectopic expression of alkaline phosphatase in proximal tubular brush border
      membrane of human renal cell carcinoma.
AB  - The present study was conducted to find out any alteration in the expression and
      activity of alkaline phosphatase in the brush border membrane (BBM) from renal
      cell carcinoma (RCC) in comparison to normal renal BBM. The specific activity of
      alkaline phosphatase was drastically reduced in homogenate as well as BBM from
      RCC kidney when compared to ALP activity in BBM of normal kidney. Kinetic studies
      revealed that diminished activity of alkaline phosphatase in BBM isolated from
      RCC was fraternized with decrease in maximal velocity (V(max)) and increase in
      affinity constant (K(m)) of the enzyme. SDS-PAGE studies showed that the BBM
      proteins having molecular weights ranging from 95 to 170 kDa were poorly
      expressed in RCC BBM in relative to normal kidney BBM. Incubation of SDS-PAGE gel
      with BCIP/NBT dye clearly showed that the expression of ALP in tumor renal BBM
      was markedly reduced as compared to normal kidney. Further, Western blot analysis
      using anti-alkaline phosphatase antibody also confirmed the reduced expression of
      ALP in tumor renal BBM. Lipid composition in reference to phospholipids,
      glycolipids and cholesterol in tumor renal BBM was altered to that of normal
      renal BBM, indicating alteration in membrane fluidity of tumor renal BBM.

PMID- 16081253
TI  - Solid-state NMR and the thermal polymerization of 2,4-hexadiyne-1,6-diol bis-(p
      toluenesulfonate).
AB  - The solid-state thermal polymerization of crystalline 2,4-hexadiyne-1,6-diol bis
      (p-toluenesulfonate) (PTS) was investigated by solid-state 13C NMR, the first
      application of this technique to such a process. The kinetics of the thermal
      process was examined at temperatures of 40.5, 51.0, and 59.5 degrees C, with a
      magic angle spinning (MAS) rate of 5 kHz. The first-order rate constants
      associated with the induction (k0) and autocatalytic (k max) periods were
      calculated by monitoring signal intensities (conversion) throughout the course of
      the thermal polymerization. While estimations of the activation energy (E(a)
      approximately 20 kcal/mol) from the NMR experiments are similar to values
      obtained by other analytical techniques, estimations of the autocatalytic effect
      (k max/k0 approximately 22) were significantly lower. Likely causes for the
      unusually small autocatalytic effect are discussed.

PMID- 16081254
TI  - Deuteron NMR spectra of ammonium ion isotopomers at low temperatures.
AB  - Partially deuterated ammonium compounds contain ammonium ion isotopomers with
      relative abundances given by the binomial distribution of protons and deuterons.
      All isotopomers with deuterons contribute characteristic deuteron NMR spectra at
      5K. Experimental NMR spectra were separated and respective contributions of
      isotopomers were determined. The derived contributions agree with expected values
      for a given deuteration in the case of ammonium hexafluorophosphate. In ammonium
      hexachlorotellurate both NH2D2+ and about 50% of NH3D+ ions are rigid, while the
      remaining NH3D+ perform limited jumps. NHD3+ and ND4+ ions undergo tunnelling
      rotation, NH3D+ ions perform either jumps about C2 axis or limited jumps, but
      some stay rigid in ammonium hexachlorostannate. NH2D2+, NHD 3+ and ND4+ undergo
      rotational tunnelling. In the case of ammonium perchlorate, the NH3D+ ions
      perform either jumps about C3 axis or limited jumps whilst some remain rigid.
      Very low values of activation energies were derived for all spectral components
      from the temperature dependence of their spectra, up to about 20K, which
      indicates an incoherent tunnelling nature of the observed dynamic processes. The
      diverse mobility of NH3D+ ions appears to be the most interesting and new
      feature.

PMID- 16081255
TI  - How do we modulate our emotions? Parametric fMRI reveals cortical midline
      structures as regions specifically involved in the processing of emotional
      valences.
AB  - One of the major problems in affective neuroscience of healthy subjects as well
      as of patients with emotional dysfunctions is to disentangle emotional core
      functions and non-emotional processes. Emotional valence is considered an
      emotional key process. The present study employed a parametric functional
      magnetic resonance imaging (fMRI) study to address this question. Thirteen
      healthy volunteers were scanned during emotional stimulus processing
      (International Affective Picture System). The presented pictures covered the
      entire range of emotional valences. The fMRI data were consecutively subjected to
      a preliminary categorical (valence-independent) and a detailed parametric
      analysis, the latter using individual valence ratings as regressor. The
      parametric analysis revealed a linear valence-dependent modulation of the BOLD
      signal in the orbito- and dorsomedial prefrontal cortex (OMPFC, DMPFC), medial
      parietal cortex (MPC), and insula. In addition, we observed that emotional
      valence exerts its effects predominantly via modulation of signal decreases. We
      conclude that the psychological concept of emotional valence may be related to
      neural processing in cortical midline regions.

PMID- 16081256
TI  - Reorganization of lipid nanocapsules at air-water interface: Part 2. Properties
      of the formed surface film.
AB  - The state, electrical and dilatational rheological properties of surface films
      formed at air-water interface from lipid nanocapsules (LNC) with various
      compositions as well as model monolayers formed by the LNC constituents-Labrafac,
      Solutol and Lipoid are investigated. These nanocapsules constitute potential drug
      delivery systems where lypophilic drug will be loaded in their core. The study of
      the model Labrafac/Solutol (Lab/Sol) mixed monolayers shows behavior close to the
      ideal. Small negative deviations in the mean molecular areas a and dipole moments
      mu are observed. All studied monolayers have elastic behavior during the small
      continuous compressions. The comparison between the properties of surface films
      formed from LNC with those of the model monolayers confirms the idea developed in
      the kinetic study that the surface films formed after a rapid disaggregation of
      the unstable nanocapsule fraction (LNC I) contains mainly Labrafac and Solutol.
      The Labrafac molar part (xLab) in the formed Lab/Sol mixed layer is established.

PMID- 16081257
TI  - Permeability of dye through poly(urea-urethane) microcapsule membrane prepared
      from mixtures of di- and tri-isocyanate.
AB  - Poly(urea-urethane) microcapsules were prepared by the interfacial polymerization
      with using mixtures of tri- and di-isocyanate monomers as wall forming materials,
      and dioctyl phthalate containing an oil-soluble dye as a core material. The time
      course of the dye release in dispersing tetrahydrofuran was measured as a
      function of the weight fraction of tri-isocyanate monomer in the total monomer w
      and the core/wall material-weight ratio g. The dye release curves were well
      represented by an exponential function C=Ceq(1-e-t/tau), where C is the
      concentration of the dye in the dispersing medium, Ceq that at equilibrium state,
      t the elution time and tau is a time constant. tau increased linearly against w
      at high g, suggesting controllability of the release rate of microcapsules by
      varying tri-isocyanate/di-isocyanate ratio.

PMID- 16081258
TI  - Electron microscopic characterization of gels formed by blood cells of leukemia
      patients at hypertonicity.
AB  - At hypertonicity some blood cells of patients suffering chronic leukemia can form
      gel like layers around themselves. These gels, which are sensitive to
      hyaluronidase, but not to trypsin are investigated by electron microscopy. The
      study revealed that the gels comprise a network of nanoparticles, which have
      diameters between 50 and 150 nm, are regularly ordered and linked to each other.

PMID- 16081259
TI  - A three step supercritical process to improve the dissolution rate of eflucimibe.
AB  - The aim of this study is to improve the dissolution properties of a poorly
      soluble active substance, Eflucimibe by associating it with gamma-cyclodextrin.
      To achieve this objective, a new three-step process based on supercritical fluid
      technology has been proposed. First, Eflucimibe and cyclodextrin are co
      crystallized using an anti-solvent process, dimethylsulfoxide being the solvent
      and supercritical carbon dioxide being the anti-solvent. Second, the co
      crystallized powder is held in a static mode under supercritical conditions for
      several hours. This is the maturing step. Third, in a final stripping step,
      supercritical CO(2) is flowed through the matured powder to extract the residual
      solvent. The coupling of the first two steps brings about a significant
      synergistic effect to improve the dissolution rate of the drug. The nature of the
      entity obtained at the end of each step is discussed and some suggestions are
      made as to what happens in these operations. It is shown the co-crystallization
      ensures a good dispersion of both compounds and is rather insensitive to the
      operating parameters tested. The maturing step allows some dissolution
      recrystallization to occur thus intensifying the intimate contact between the two
      compounds. Addition of water is necessary to make maturing effective as this is
      governed by the transfer properties of the medium. The stripping step allows
      extraction of the residual solvent but also removes some of the Eflucimibe which
      is the main drawback of this final stage.

PMID- 16081260
TI  - [Is non IgE-dependent sensitization to cow's milk proteins responsible for
      resistant idiopathic vulvitis of young girls?].

PMID- 16081261
TI  - Highly accurate and consistent method for prediction of helix and strand content
      from primary protein sequences.
AB  - OBJECTIVE: One of interesting computational topics in bioinformatics is
      prediction of secondary structure of proteins. Over 30 years of research has been
      devoted to the topic but we are still far away from having reliable prediction
      methods. A critical piece of information for accurate prediction of secondary
      structure is the helix and strand content of a given protein sequence. Ability to
      accurately predict content of those two secondary structures has a good potential
      to improve accuracy of prediction of the secondary structure. Most of the
      existing methods use composition vector to predict the content. Their underlying
      assumption is that the vector can be used to provide functional mapping between
      primary sequence and helix/strand content. While this is true for small sets of
      proteins we show that for larger protein sets such mapping are inconsistent, i.e.
      the same composition vectors correspond to different contents. To this end, we
      propose a method for prediction of helix/strand content from primary protein
      sequences that is fundamentally different from currently available methods.
      METHODS AND MATERIAL: Our method is accurate and uses a novel approach to obtain
      information from primary sequence based on a composition moment vector, which is
      a measure that includes information about both composition of a given primary
      sequence and the position of amino acids in the sequence. In contrast to the
      composition vector, we show that it provides functional mapping between primary
      sequence and the helix/strand content. RESULTS: A set of benchmarks involving a
      large protein dataset consisting of over 11,000 protein sequences from Protein
      Data Bank was performed to validate the method. Prediction done by a neural
      network had average accuracy of 91.5% for the helix and 94.5% for the strand
      contents. We also show that using the new measure results in about 40% reduction
      of error rates when compared with the composition vector results. CONCLUSIONS:
      The developed method has much better accuracy when compared with other existing
      methods, as shown on a large body of proteins, in contrast to other reported
      results that often target small sets of specific protein types, such as globular
      proteins.

PMID- 16081262
TI  - Increased excretion of a lipid peroxidation biomarker in autism.
AB  - It is thought that autism could result from an interaction between genetic and
      environmental factors with oxidative stress as a potential mechanism linking the
      two. One genetic factor may be altered oxidative-reductive capacity. This study
      tested the hypothesis that children with autism have increased oxidative stress.
      We evaluated children with autism for the presence of two oxidative stress
      biomarkers. Urinary excretion of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8
      isoprostane-F2alpha (8-iso-PGF2alpha) were determined in 33 children with autism
      and 29 healthy controls. 8-iso-PGF2alpha levels were significantly higher in
      children with autism. The isoprostane levels in autistic subjects were variable
      with a bimodal distribution. The majority of autistic subjects showed a moderate
      increase in isoprostane levels while a smaller group of autistic children showed
      dramatic increases in their isoprostane levels. There was a trend of an increase
      in 8-OHdG levels in children with autism but it did not reach statistical
      significance. There was no significant correlation between the levels of the
      biomarkers and vitamin intake, dietary supplements, medicine, medical disorders,
      or history of regression. These results suggest that the lipid peroxidation
      biomarker is increased in this cohort of autistic children, especially in the
      subgroup of autistic children.

PMID- 16081263
TI  - Expression levels of ACAT1 and ACAT2 genes in the liver and intestine of baboons
      with high and low lipemic responses to dietary lipids.
AB  - Acyl-coenzyme A:cholesterol acyltransferase (ACAT) 1 and ACAT2 play an important
      role in cellular cholesterol esterification and thus modulate intestinal
      cholesterol absorption and hepatic lipoprotein secretion. The relative expression
      levels of ACAT1 and ACAT2 in human tissues differ from those in other animals,
      including nonhuman primates. The present study compared the relative expression
      levels of ACAT1 and ACAT2 in baboons with high and low lipemic responses to
      dietary lipids. We isolated RNA and prepared cDNA from frozen liver and small
      intestine from high- and low-responding pedigreed baboons necropsied after
      consuming a high-cholesterol and high-fat diet for 18 months. The expression of
      ACAT1 and ACAT2 was measured by TaqMan real-time quantitative PCR normalized to
      18s ribosomal RNA. The expression of ACAT1 was higher than that of ACAT2 in the
      liver, whereas the expression of ACAT2 was higher than that of ACAT1 in the
      duodenum and jejunum. There was no difference in the expression of ACAT1 or ACAT2
      in the liver and intestine between high- and low-responding baboons except that
      the expression of ACAT1 was higher in the duodenum of high responders than in
      that of low responders. Western blot analysis also showed a higher level of ACAT1
      protein in the duodenum of high responders than in that of low responders. There
      was a significant correlation between duodenal ACAT expression levels and total
      plasma cholesterol concentration in baboons. These results suggest that
      differences in ACAT1 expression may affect plasma cholesterol concentration and
      partly affect diet-induced hyperlipidemia.

PMID- 16081264
TI  - Modulation of carbohydrate metabolism and peptide hormones by soybean isoflavones
      and probiotics in obesity and diabetes.
AB  - Soybean and its isoflavones have been shown to have beneficial effects on
      carbohydrate and lipid metabolism and on renal function. Probiotics may
      potentiate the beneficial effects of isoflavones by converting the inactive
      isoflavone glycoside to aglycones, which are biologically active, thereby
      producing a synergistic effect. We therefore studied the effects of soybean
      isoflavones in the presence and absence of probiotics on glucose and triglyceride
      metabolism and the peptide hormones involved in their metabolism. Lean and obese
      SHR/N-cp rats were fed AIN-93 diets containing 0.1% soybean isoflavone mixture,
      0.1% probiotics mixture or both. Plasma was analyzed for glucose, triglycerides,
      parameters of renal function and peptide hormones -- insulin, leptin, glucagon
      and ACTH -- that are involved in glucose and lipid metabolism. Isoflavones given
      alone lowered plasma glucose in both phenotypes while triglyceride was decreased
      only in lean animals. Isoflavones also lowered aspartate amino transferase and
      alanine amino transferase in both phenotypes. Isoflavones had significant effect
      on plasma insulin, leptin and glucagon in lean rats but not in obese rats. Thus,
      our data show that in lean animals, isoflavones have hypoglycemic and
      hypolipidemic effect, and the effect is mediated by changes in peptide hormones.
      When lipid levels are very high as in obese rats, isoflavones fail to lower
      plasma triglyceride levels. Probiotics do not appear to enhance the effect of
      isoflavones.

PMID- 16081265
TI  - Hyperglycinemia due to folate deficiency in rats: evidence for the lack of
      involvement of the hepatic glycine cleavage system.
AB  - In addition to a well-recognized hyperhomocysteinemic state, folate deficiency
      also leads to profound hyperglycinemia. To further characterize the latter
      observation, two trials were conducted using a folate-deficient rat model to (1)
      determine the sensitivity of plasma glycine to folate repletion and (2) test the
      hypothesis that hyperglycinemia results from a reduced flux through the folate
      dependent glycine cleavage system (GCS). Weanling male Sprague-Dawley rats were
      used, and they consumed an amino acid-defined diet with either 0 (FD) or 1 (FA)
      mg/kg of crystalline folic acid. In Trial 1, 30 rats consumed the FD diet for 28
      days. Rats then consumed diets containing 0.1, 0.2, 0.3 or 0.4 mg/kg of folic
      acid for 14 days before termination. In Trial 2, 16 rats were allocated to
      receive either the FA (n=8) or FD (n=8) diet for 30 days before termination.
      Liver mitochondria were isolated and flux through the GCS (measured as 14CO2
      production from 1-14C-glycine) was determined. Plasma from blood collected at
      termination was analyzed for folate, homocysteine and glycine. In Trial 1, both
      homocysteine and glycine responded linearly to increased dietary folic acid
      (milligrams per kilogram) levels (P<.05). In Trial 2, plasma folate (FA=25.85 vs.
      FD=0.66; S.E.M.=1.4 microM), homocysteine (FA=11.1 vs. FD=55.3; S.E.M.=1.7
      microM) and glycine (FA=564 vs. FD=1983; S.E.M.=114 microM) were significantly
      affected by folate deficiency (P<.0001). However, glycine flux through hepatic
      GCS was not affected by folate deficiency (P>.05). These results provide evidence
      that in a folate-deficient rat model, both homocysteine and glycine are sensitive
      to dietary folic acid levels; however, the observed hyperglycinemia does not
      appear to be related to a reduced flux through the hepatic GCS.

PMID- 16081266
TI  - Effect of food restriction on the insulin signalling pathway in rat skeletal
      muscle and adipose tissue.
AB  - We tried to elucidate the effects of a brief and severe model of food restriction
      on insulin sensitivity in female rats, focusing on key proteins involved in the
      insulin signalling pathway in skeletal muscle and adipose tissue after 5, 10 and
      15 days of food restriction. Using euglycemic clamp, we detected that food
      restricted rats are significantly less sensitive to insulin action than control
      rats. However, the time of restriction promotes a progressive increase on insulin
      sensitivity. The analysis of the insulin signalling pathway showed a tissue
      specific regulation of several proteins involved in insulin signalling. In
      skeletal muscle, insulin receptor substrate 1 and Glut4 are up-regulated at the
      end of the food restriction period, just the opposite of what we found in adipose
      tissue. In conclusion, a 50% reduction of food intake modulates insulin
      sensitivity through a tissue-specific regulation of the insulin signalling
      pathway in the main target tissues for this hormone.

PMID- 16081267
TI  - Reduction of oxidative stress and apoptosis in hyperlipidemic rabbits by ellagic
      acid.
AB  - Oxidative stress is one of the major risk factors for coronary artery disease.
      Ellagic acid is a phenolic compound present in fruits and nuts, and has been
      found to have antioxidative property. Twenty-four New Zealand white (NZW) rabbits
      were assigned randomly into four dietary groups. The normal group was fed regular
      rabbit chow, and the cholesterol group was fed a high fat and cholesterol diet.
      The ellagic acid (E) group and probucol group were fed the same diet as the
      cholesterol group plus the addition of 1% (w/w diet) ellagic acid and probucol,
      respectively. Oxidative stress [as measured by plasma lipids, oxygen free
      radicals and thiobarbituric acid reactive substances (TBARS)] increased in the
      cholesterol group compared with the normal group; however, it decreased in the
      probucol and E groups compared with the cholesterol group. Forty-five percent of
      the intimal surface of the thoracic aorta was covered with atherosclerotic
      lesions in the cholesterol group, but only 2-3% was covered in the E and probucol
      groups. The aortic level of 8-(OH)dG and the expression of caspase-8, caspase-9
      and Fas ligand were also suppressed after ellagic acid supplement. These results
      indicated that ellagic acid could prevent atherosclerosis via suppression of
      oxidative stress and apoptosis in hyperlipidemic rabbits.

PMID- 16081268
TI  - Resveratrol modulates gene expression associated with apoptosis, proliferation
      and cell cycle in cells with mutated human c-Ha-Ras, but does not alter c-Ha-Ras
      mRNA or protein expression.
AB  - An accumulating body of evidence suggests that resveratrol can inhibit
      carcinogenesis through antiproliferative and apoptotic effects. One proposed
      mechanism for this is the modulation of genes, for example, Ras and p53,
      frequently associated with human cancer. To test the effect of resveratrol on
      gene expression, we used the WR-21 cell line because it contains a mutated human
      c-Ha-ras gene. Cells at > or =70% confluency were incubated with media alone or
      with increasing concentrations of trans-resveratrol (0.1-1000 microM) for 24 h.
      Resveratrol (30-100 microM) decreased cellular proliferation by 80%
      (bromodeoxyuridine incorporation) and increased apoptosis by 60% (TUNEL). Cells
      were then treated with media alone or with 50-microM resveratrol for 24 h. RNA
      was isolated for nylon-based macroarray analyses and protein for immunoblotting.
      Resveratrol increased (+) and decreased (-) gene expression associated with
      apoptosis (Birc5+, Cash+, Mcl-1+, Mdm2+, Rpa-like+), cellular proliferation
      (Ctsd+, Mdm2+, Egr1+, ODC+) and cell cycle (cyclin D+, cyclin g+, Gadd45a-, Mad2l
      , Mdm2+). Resveratrol consistently increased by > or =6-fold Mdm2 expression and
      other downstream p53 effectors, but not p53 itself at 24 h. Subsequent cell cycle
      analysis indicated a significant accumulation of cells in G2/M, and a decrease in
      G1/G0 suggesting a G2/M blockade. Further RT-PCR and Western blot analyses
      indicated no differential changes in Ras mRNA expression or p21(ras) protein
      levels, respectively. These results suggest that resveratrol potently inhibits
      cellular proliferation, increases apoptosis, alters cell cycle dynamics and
      modulates associated gene expression. Furthermore, these effects appear mediated,
      in part, by p53 without direct modulation of mutant c-Ha-ras expression.

PMID- 16081269
TI  - HepG2 cells develop signs of riboflavin deficiency within 4 days of culture in
      riboflavin-deficient medium.
AB  - Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are essential
      coenzymes in redox reactions. For example, FAD is a coenzyme for both glutathione
      reductase and enzymes that mediate the oxidative folding of secretory proteins.
      Here we investigated short-term effects of moderately riboflavin-deficient
      culture medium on flavin-related responses in HepG2 hepatocarcinoma cells. Cells
      were cultured in riboflavin-deficient (3.1 nmol/l) medium for up to 6 days;
      controls were cultured in riboflavin-sufficient (532 nmol/l) medium. The activity
      of glutathione reductase decreased by 98% within 4 days of riboflavin-deficient
      culture. Transport rates of riboflavin increased in response to riboflavin
      depletion, whereas expression of enzymes mediating flavocoenzyme synthesis
      (flavokinase and FAD synthetase) decreased in response to depletion. The
      oxidative folding and synthesis of plasminogen and apolipoprotein B-100 was
      impaired within 4 days of culture in riboflavin-deficient medium; this is
      consistent with impaired processing of secretory proteins in riboflavin-deficient
      cells. Riboflavin depletion was associated with increased DNA-binding activities
      of transcription factors with affinity for endoplasmic reticulum stress elements
      and nuclear factor kappaB (NF-kappaB) consensus elements, suggesting cell stress.
      Moreover, the abundance of the stress-induced protein GADD153 was greater in
      riboflavin-deficient cells compared with controls. Riboflavin deficiency was
      associated with decreased rates of cell proliferation caused by arrest in G1
      phase of the cell cycle. These studies are consistent with the hypothesis that
      HepG2 cells have a great demand for riboflavin and that cell stress develops
      rapidly if riboflavin supply is marginally low.

PMID- 16081270
TI  - Bioavailability and antioxidant effect of epigallocatechin gallate administered
      in purified form versus as green tea extract in healthy individuals.
AB  - Tea polyphenols have strong in vitro antioxidant activity. Due to their limited
      bioavailability, however, their contribution to in vivo antioxidant activity may
      depend on the form of administration. A human intervention study was performed to
      evaluate the bioavailability and antioxidant capacity of (-)-epigallocatechin-3
      gallate (EGCG) administered as a single large dose in the form of either purified
      EGCG or as green tea extract (Polyphenon E). Plasma concentrations of tea
      polyphenols were determined by high-performance liquid chromatography (HPLC)
      analysis combined with coulometric array electrochemical detection (ECD). We
      found no differences in plasma EGCG concentrations and trolox equivalents
      determined by the trolox equivalent antioxidant capacity assay after
      administration of either form of EGCG. However, we found that the plasma
      antioxidant activity was significantly affected by changes in the plasma urate
      concentration, which may have interfered with the effect of tea polyphenols on
      the antioxidant activity. In addition, lymphocyte 8-hydroxydeoxyguanosine to
      deoxyguanosine (8-OHdG/10(6)dG) ratios were determined by HPLC with ECD. The 8
      OHdG/10(6)dG ratios did not change significantly during the 24 h following both
      EGCG interventions but correlated significantly within individuals determined
      during the two interventions separated by 1 week. In summary, changes in plasma
      uric acid due to dietary intake were significantly correlated to the plasma
      antioxidant activity and exerted a stronger influence on the plasma antioxidant
      activity compared with the EGCG intervention. In future studies of dietary
      effects on the plasma antioxidant capacity, changes in plasma uric acid will need
      to be closely monitored.

PMID- 16081271
TI  - Uterine phenotype of young adult rats exposed to dietary soy or genistein during
      development.
AB  - Dietary soy intake is associated with protection from breast cancer, but
      questions persist on the potential risks of the major soy isoflavone genistein
      (GEN) on female reproductive health. Here, we evaluated intermediate markers of
      cancer risk in uteri of cycling, young adult Sprague-Dawley rats lifetime exposed
      to one of three AIN-93G semipurified diets: casein (CAS), soy protein isolate
      (SPI+ with 276 mg GEN aglycone equivalents/kg) and CAS+GEN (GEN at 250 mg/kg).
      Postnatal day 50 (PND50) rats lifetime exposed to GEN or SPI+ had similar uterine
      luminal epithelium height, myometrial thickness, endometrial gland numbers,
      endometrial immunoreactive proliferating cell nuclear antigen (PCNA), and serum
      estrogen and progesterone, as CAS-fed rats. GEN-fed rats showed modestly
      increased apoptosis in uterine glandular epithelium, compared to those of CAS- or
      SPI+-fed groups. Diet had no effect on the uterine expression of genes for the
      tumor suppressors PTEN, p53 and p21, and the apoptotic-associated proteins Bcl2,
      Bax and progesterone receptor. Uterine tissue and serum concentrations of total
      GEN were higher in rats fed GEN than in those fed SPI+. Human Ishikawa
      endocarcinoma cells treated with GEN-fed rat serum tended to exhibit increased
      apoptotic status than those treated with CAS-fed rat serum. Exogenously added GEN
      (0.2 and 2 microM) increased, while estradiol-17beta (0.1 microM) decreased
      Ishikawa cell apoptosis, relative to untreated cells. Results suggest that
      lifetime dietary exposure to soy foods does not alter uterine cell phenotype in
      young adult rats, while GEN, by enhancing uterine endometrial glandular apoptosis
      in vivo and in vitro, may confer protection against uterine carcinoma. Given its
      limited influence on uterine phenotype of young adult females, GEN, when taken as
      part of soy foods or as supplement, should be favorably considered for other
      potential health benefits.

PMID- 16081272
TI  - Different palm oil preparations reduce plasma cholesterol concentrations and
      aortic cholesterol accumulation compared to coconut oil in hypercholesterolemic
      hamsters.
AB  - Several studies have reported on the effect of refined, bleached and deodorized
      palm oil (RBD-PO) incorporation into the diet on blood cholesterol concentrations
      and on the development of atherosclerosis. However, very little work has been
      reported on the influence of red palm oil (RPO), which is higher in carotenoid
      and tocopherol content than RBD-PO. Thus, we studied the influence of RPO, RBD-PO
      and a RBD-PO plus red palm oil extract (reconstituted RBD-PO) on plasma
      cholesterol concentrations and aortic accumulation vs. hamsters fed coconut oil.
      Forty-eight F1B Golden Syrian hamsters (Mesocricetus auratus) (BioBreeders,
      Watertown, MA) were group housed (three/cage) in hanging polystyrene cages with
      bedding in an air-conditioned facility maintained on a 12-h light/dark cycle. The
      hamsters were fed a chow-based hypercholesterolemic diet (HCD) containing 10%
      coconut oil and 0.1% cholesterol for 2 weeks at which time they were bled after
      an overnight fast and segregated into four groups of 12 with similar plasma
      cholesterol concentrations. Group 1 continued on the HCD, Group 2 was fed the HCD
      containing 10% RPO in place of coconut oil, Group 3 was fed the HCD containing
      10% RBD-PO in place of coconut oil and Group 4 was fed the HCD with 10%
      reconstituted RBD-PO for an additional 10 weeks. Plasma total cholesterol (TC)
      and non-high-density lipoprotein-cholesterol (HDL-C) (very low- and low-density
      lipoprotein) concentrations were significantly lower in the hamsters fed the RPO
      (-42% and -48%), RBD-PO (-32% and -36%) and the reconstituted RBD-PO (-37% and 
      41%) compared to the coconut oil-fed hamsters. Plasma HDL-C concentrations were
      significantly higher by 14% and 31% in hamsters fed the RBD-PO and RPO compared
      to the coconut oil-fed hamsters. Plasma triglyceride (TG) concentrations were
      significantly lower in hamsters fed RBD-PO (-32%) and the reconstituted RBD-PO (
      31%) compared to the coconut oil-fed hamsters. The plasma gamma-tocopherol
      concentrations were higher in the coconut oil-fed hamsters compared to the
      hamsters fed the RPO (60%), RBD-PO (42%) and the reconstituted RBD-PO (49%),
      while for plasma alpha-tocopherol concentrations, the coconut oil-fed hamsters
      were significantly higher than only the RPO-fed hamsters (21%). The coconut oil
      fed hamsters also had significantly higher plasma lipid hydroperoxide
      concentrations compared to RBD-PO (112%) and the reconstituted RBD-PO (485%). The
      hamsters fed the coconut oil diet excreted significantly more fecal total neutral
      sterols and cholesterol compared to the hamsters fed the RBD-PO (158% and 167%,
      respectively). The coconut oil-fed hamsters had significantly higher levels of
      aortic total, free and esterified cholesterol compared to the hamsters fed the
      RPO (74%, 50% and 225%, respectively), RBD-PO (57%, 48% and 92%, respectively)
      and the reconstituted RBD-PO (111%, 94% and 94%, respectively). Also, aortic
      free/ester cholesterol ratio in the aortas of hamsters fed RPO was significantly
      higher than in those fed the coconut oil (124%). In conclusion, hamsters fed the
      three palm oil preparations had lower plasma TC and non-HDL-C and higher HDL-C
      concentrations while accumulating less aortic cholesterol concentrations compared
      to hamsters fed coconut oil.

PMID- 16081273
TI  - Serum superoxide dismutase 3 (extracellular superoxide dismutase) activity is a
      sensitive indicator of Cu status in rats.
AB  - Sensitivity of the assay for Cu,Zn superoxide dismutase 3 (SOD3), the predominant
      form of SOD in serum, can be increased, and interferences caused by low-molecular
      weight substances in the serum can be reduced by conducting the assay at pH 10
      with xanthine/xanthine oxidase and acetylated cytochrome c (cyt c) as superoxide
      generator and detector, respectively. Serum SOD3 activity was assayed under these
      conditions in an experiment where weanling, male rats were fed diets for 6 weeks
      containing 3, 5 and 15 mg Zn/kg with dietary Cu set at 0.3, 1.5 and 5 mg Cu/kg at
      each level of dietary Zn. Serum SOD3 responded to changes in dietary Cu but not
      to changes in dietary Zn. A second experiment compared serum SOD3 activity to
      traditional indices of Cu status in weanling, male and female rats after they
      were fed diets containing, nominally, 0, 1, 1.5, 2, 2.5, 3 and 6 mg Cu/kg for 6
      weeks. Serum SOD3 activity was significantly lower (P < .05) in male rats fed
      diets containing 0 and 1 mg Cu/kg and female rats fed diet containing 0 mg Cu/kg
      compared with rats fed diet containing 6 mg Cu/kg. These changes were similar to
      changes in liver Cu concentrations, liver cyt c oxidase (CCO) activity and plasma
      ceruloplasmin in males and females. Serum SOD3 activity was also strongly,
      positively correlated with liver Cu concentrations over the entire range of
      dietary Cu concentrations (R(2) = .942 in males, R(2) = .884 in females, P <
      .0001). Plots of serum SOD3 activity, liver Cu concentration, liver CCO activity
      and ceruloplasmin as functions of kidney Cu concentration all had two linear
      segments that intersected at similar kidney Cu concentrations (18-22 microg/g dry
      kidney in males, 15-17 microg/g dry kidney in females). These findings indicate
      that serum SOD3 activity is a sensitive index of Cu status.

PMID- 16081274
TI  - The expression of genes encoding ribosomal subunits and eukaryotic translation
      initiation factor 5A depends on biotin and bisnorbiotin in HepG2 cells.
AB  - Biotin affects gene expression at both the transcriptional and the
      posttranscriptional level; biotin metabolites might have biotin-like activities
      with regard to gene expression. Here, human hepatocarcinoma (HepG2) cells were
      used (i) to identify clusters of biotin-dependent genes, (ii) to determine
      whether the naturally occurring metabolite bisnorbiotin affects gene expression
      and (iii) to determine whether biotin and bisnorbiotin affect the expression of
      genes coding for ribosomal subunits and translation initiation factors. HepG2
      cells were cultured in media containing deficient (0.025 nmol/L), physiological
      (0.25 nmol/L, control) and pharmacological (10 nmol/L) concentrations of biotin;
      a fourth treatment group consisted of cells cultured in biotin-deficient medium
      (0.025 nmol/L) supplemented with bisnorbiotin (0.225 nmol/L). Gene expression was
      quantified by using DNA microarrays and reverse transcriptase polymerase chain
      reaction. The expression of 1803 genes depended on biotin concentrations in
      culture media; the expression of 618 genes depended on bisnorbiotin. Biotin
      deficiency was associated with increased expression of a gene cluster encoding
      ribosomal subunits and eukaryotic translation initiation factor 5A; this effect
      was reversed by supplementation with biotin and bisnorbiotin. Additional
      prominent clusters of (bisnor)biotin-dependent genes included DNA-, RNA-, and
      nucleotide-binding proteins, consistent with a role for biotin in cell signaling
      and gene expression. Collectively, these data suggest that bisnorbiotin has
      biotin-like activities regarding gene expression, and that clusters of
      (bisnor)biotin-dependent genes include genes that play roles in translational
      activity.

PMID- 16081275
TI  - Inhibitory effects of glycolipids fraction from spinach on mammalian DNA
      polymerase activity and human cancer cell proliferation.
AB  - We succeeded in purifying the fraction containing the major glycolipids in
      monogalactosyl diacylglycerol, digalactosyl diacylglycerol and sulfoquinovosyl
      diacylglycerol (SQDG) from dried vegetables. This glycolipids fraction was an
      inhibitor of DNA polymerase alpha (pol alpha) in vitro and also the proliferation
      of human cancer cells. In this study, eight common vegetables were investigated
      in terms of the glycolipids fraction, the amounts of major glycolipids, mammalian
      DNA polymerase inhibitory activity and antiproliferative activity toward human
      cancer cells. Green tea possessed the largest amount of glycolipids overall.
      Spinach contained the largest amount of SQDG, followed by parsley, green onion,
      chive, sweet pepper, green tea, carrot and garlic. Spinach had the strongest
      inhibitory effect on pol alpha activity and human cancer cell proliferation. A
      significant correlation was found between SQDG content and inhibition of DNA
      polymerase. Therefore, the inhibition of pol alpha activity by SQDG may lead to
      cell growth suppression. Of the six subspecies of spinach (Spinacia oleracea)
      tested, "Anna" had the largest amount of SQDG, strongest inhibitory activity
      toward DNA polymerase and greatest effect on human cancer cell proliferation.
      Based on these results, the glycolipids fraction from spinach is potentially a
      source of food material for a novel anticancer activity.

PMID- 16081276
TI  - Bacterially synthesized folate and supplemental folic acid are absorbed across
      the large intestine of piglets.
AB  - A large pool of folate exists in the large intestine of humans. Preliminary
      evidence, primarily in vitro, suggests that this folate may be bioavailable. The
      purpose of this study was to test the hypothesis that supplemental folic acid and
      bacterially synthesized folate are absorbed across the large intestine of
      piglets. The pig was used as an animal model because it resembles the human in
      terms of folate absorption, at least in the small intestine. A tracer of [3H]
      folic acid or [3H]-para-aminobenzoic acid ([3H]-PABA), a precursor of bacterially
      synthesized folate, was injected into the cecum of 11-day-old piglets. Feces and
      urine were collected for 3 days. Thereafter, piglets were killed, and livers and
      kidneys harvested. [3H]-Folate was isolated from biological samples by affinity
      chromatography using immobilized milk folate binding proteins and counted using a
      scintillation counter. In piglets injected with [3H]-folic acid, the feces,
      liver, urine and kidneys accounted for 82.1%, 12.3%, 3.9% and 1.7% of recovered
      [3H]-folate, respectively. In piglets injected with [3H]-PABA, the amount of
      recovered bacterially synthesized folate in the feces, liver and urine was 85.1%,
      0.4% and 14.6%, respectively. Twenty-three percent and 13% of tritium were
      recovered in samples examined (liver, kidney, fecal and urine) from piglets
      injected with [3H]-folic acid and [3H]-PABA, respectively. Using our estimates of
      [3H]-folic acid absorption and the total and percent monoglutamyl folate content
      of piglet feces, we predict that at least 18% of the dietary folate requirement
      for the piglet could be met by folate absorption across the large intestine.

PMID- 16081277
TI  - New concepts in the chromatography of peptides and proteins.
AB  - Although chromatography using a variety of novel bed configurations (e.g.
      fluidized beds, expanded beds, simulated moving beds, annular rotating beds,
      etc.) has been of recent interest, the majority of practical applications of
      analytical and preparative chromatography employ a stationary adsorbent bed into
      which a feed slug is charged periodically, similar to the technique first
      described by Mikhail Tswett over 100 years ago. However, new concepts in both the
      practice and theory of fixed-bed chromatography are continuing to expand the
      available range of applications for separating peptides and proteins.

PMID- 16081278
TI  - E2F-Rb complexes regulating transcription of genes important for differentiation
      and development.
AB  - Inactivation of the retinoblastoma tumour suppressor protein (pRb) is a hallmark
      of most human cancers. Accordingly, pRb is serving as a paradigm in our quest to
      understand tumour suppressor function. The role played by pRb and the related
      'pocket proteins', p107 and p130, in regulating cell cycle progression has been
      extensively studied over the past two decades. The function of pRb in regulating
      transcriptional programmes in differentiating cells is less well understood.
      Recently, the use of a variety of different cell, animal and plant model systems
      has allowed us a first glimpse at some of the molecular mechanisms underlying pRb
      mediated transcriptional regulation during differentiation and development.

PMID- 16081279
TI  - Curcumin: the story so far.
AB  - Curcumin is a polyphenol derived from the herbal remedy and dietary spice
      turmeric. It possesses diverse anti-inflammatory and anti-cancer properties
      following oral or topical administration. Apart from curcumin's potent
      antioxidant capacity at neutral and acidic pH, its mechanisms of action include
      inhibition of several cell signalling pathways at multiple levels, effects on
      cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno
      modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability
      to affect gene transcription and to induce apoptosis in preclinical models is
      likely to be of particular relevance to cancer chemoprevention and chemotherapy
      in patients. Although curcumin's low systemic bioavailability following oral
      dosing may limit access of sufficient concentrations for pharmacological effect
      in certain tissues, the attainment of biologically active levels in the
      gastrointestinal tract has been demonstrated in animals and humans. Sufficient
      data currently exist to advocate phase II clinical evaluation of oral curcumin in
      patients with invasive malignancy or pre-invasive lesions of the gastrointestinal
      tract, particularly the colon and rectum.

PMID- 16081280
TI  - A robust characterization of retinoic acid response elements based on a
      comparison of sites in three species.
AB  - The availability of high-throughput genomic sequencing has allowed us to
      construct a more robust characterization of retinoic acid response elements than
      was possible in the past. We located human, mouse, and rat homologs for each of
      51 well-documented, conserved retinoic acid response elements. Mathematical and
      statistical analyses of these 153 sites, 78 of which are new, shows that 92% of
      response elements have direct-repeat symmetry, but that only 76% exhibit
      canonical spacing attributes. While the familiar '(a/g)g(g/t)tca' hexamer motif
      is upheld, the more relaxed sequence, '(a/g)g(g/t)(g/t)(g/c)a', represents a 10%
      consensus. Sites are as likely to be on the coding strand as on the non-coding
      strand, and 86% of them are in upstream locations. From a statistical point of
      view, DR1 elements are fundamentally different from DR2 and DR5 elements, but
      this is only evident in the 5' hexamer. While there is considerable variation in
      core positions, and while no nucleotide can be considered forbidden at any
      position, variation among species at a fixed locus appears surprisingly
      constrained once a functional site has been attained.

PMID- 16081281
TI  - Inhibition of prostate cancer-meditated osteoblastic bone lesions by the low
      calcemic analog 1alpha-hydroxymethyl-16-ene-26,27-bishomo-25-hydroxy vitamin D3.
AB  - Prostate cancer metastasizes almost exclusively into the bone whereby it induces
      primarily an osteoblastic response. Non-calcemic vitamin D analogs have been
      shown to inhibit proliferation of prostate cancer cells in culture and inhibit
      their growth as subcutaneous xenografts in mice. However, their effect on
      prostate cancer cell growth in the bone has not been examined. In the present
      study, we inoculated the osteoblastic prostate cancer cell line MDA-PCa 2b into
      the bone of male SCID mice and examined the effect of the low-calcemic hybrid
      analog 1alpha-hydroxymethyl-16-ene-26,27-bishomo-25-hydroxy vitamin D(3) (JK-1626
      2) on their ability to induce bone lesions. We found that 7 weeks after
      inoculation of MDA-PCa 2b cells, 90% of the mice in the vehicle-treated group had
      significant bone lesions that were detectable by micro-computed tomography and
      characterized by thickening of the cortical bone and ossification of the
      epiphysis. Only 30% of the mice in the analog-treated group (daily injections of
      4microg/kg, 5 days/week for up to 7 weeks) had detectable bone lesions.
      Histological examination of the decalcified tumor-bearing bones has shown that
      tumor cells completely replaced the bone marrow in the diaphysis, and destroyed
      the trabecular bone in the metaphysis in 90% of the vehicle-treated mice. In
      contrast, the metaphysis of 60% of analog-treated mice appeared normal, although
      tumor cells were still found in the diaphysis of 70% of the bones in the analog
      treated group. There was no evidence of hypercalcemia in any of the analog
      treated mice. In a co-culture, MDA-PCa 2b cells induced a profound mitogenic
      response in osteoblasts followed by enhanced differentiation. However, in the
      presence of the analog the mitogenic response of the osteoblasts to the malignant
      cells was significantly attenuated. These experiments led to the hypothesis that,
      in vivo, JK-1626-2 prevented the metastatic bone lesions by inhibiting the
      mitogenic response of osteoblasts to growth factors produced by MDA-PCa 2b cells.

PMID- 16081282
TI  - The Vitamin D endocrine system of the gut--its possible role in colorectal cancer
      prevention.
AB  - While Vitamin D insufficiency in the US and European population is rising,
      epidemiological studies suggest an inverse correlation between low serum levels
      of 25-hydroxyvitamin D(3) (25-OH-D(3)) and colorectal cancer incidence. The
      antimitotic, prodifferentiating and proapoptotic active metabolite 1alpha,25
      dihydroxyvitamin D(3) (1,25-(OH)(2)-D(3)) is synthesized also by colonocytes,
      since these possess Vitamin D synthesizing (CYP27B1) and catabolic (CYP24)
      hydroxylases similar to the kidney. Early during colon tumor progression,
      expression of CYP27B1 and of the Vitamin D receptor increases, suggesting an
      autocrine/paracrine growth control in colon tissue as a physiological restriction
      against tumor progression. However, in human adenocarcinomas expression of the
      catabolic CYP24 is also enhanced when compared with adjacent normal mucosa.
      Therefore, to maintain colonic accumulation of 1,25-(OH)(2)-D(3) its catabolism
      needs to be restricted. Our studies in mice show that low nutritional calcium
      causes hyperproliferation of colon crypts and significant elevation of CYP24
      expression, which can be completely abrogated by soy feeding. We suggest that
      phytoestrogens in soy, known to be estrogen receptor modulators, are responsible
      for decreased CYP24 expression. These results and our observation that 17beta
      estradiol can elevate CYP27B1 expression in rectal tissue of postmenopausal
      women, may underlie the observed protective effect of estrogens against
      colorectal cancer in females.

PMID- 16081283
TI  - Biological actions of extra-renal 25-hydroxyvitamin D-1alpha-hydroxylase and
      implications for chemoprevention and treatment.
AB  - The Vitamin D-activating enzyme 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha
      hydroxylase) is now known to be expressed in a much wider range of tissues that
      previously thought, suggesting a role for 1,25-dihydroxyvitamin D(3)
      (1,25(OH)(2)D(3)), which is more in keeping with a cytokine than a hormone. In
      this capacity, the function of 1alpha-hydroxylase in tumors is far from clear.
      Studies from several groups including ours have shown altered expression of
      1alpha-hydroxylase in different types of neoplasm including breast, prostate and
      colon cancers. However, functional analysis of Vitamin D metabolism in cancer is
      complicated by the heterogenous composition of tumors. Immunohistochemical
      analysis of breast tumors has shown that 1alpha-hydroxylase is expressed by both
      epithelial cells and by tumor-infiltrating macrophages, suggesting an
      immunomodulatory component to 1,25(OH)(2)D(3) production in some types of cancer.
      The demonstration of 1alpha-hydroxylase activity in tumors and their equivalent
      normal tissues has implications for both the treatment and prevention of cancers.
      For example, in tumors chemotherapy options may include the use of non-1alpha
      hydroxylated Vitamin D analogs to increase local concentrations of active
      metabolites without systemic side-effects. The role of 1alpha-hydroxylase in
      protection against cancer is likely to be more complicated and may involve anti
      tumor immune responses.

PMID- 16081284
TI  - Calcium signaling in cancer and vitamin D.
AB  - Calcium signals induced by the Ca(2+) regulatory hormone 1,25(OH)(2)D(3) may
      determine the fate of the cancer cell. We have shown that, in breast cancer cell
      lines, 1,25(OH)(2)D(3) induces a sustained increase in concentration of
      intracellular Ca(2+) ([Ca(2+)](i)) by depleting the endoplasmic reticulum (ER)
      Ca(2+) stores via inositol 1,4,5-trisphosphate receptor/Ca(2+) release channel
      and activating Ca(2+) entry from the extracellular space via voltage-insensitive
      Ca(2+) channels. In normal cells, 1,25(OH)(2)D(3) triggered a transient Ca(2+)
      response via activation of voltage-dependent Ca(2+) channels, which were absent
      in breast cancer cells. The normal cells, but not breast cancer cells, expressed
      the Ca(2+) binding/buffering protein calbindin-D(28k) and were capable of
      buffering [Ca(2+)](i) increases induced by a mobilizer of the ER Ca(2+) stores,
      thapsigargin, or a Ca(2+) ionophore, ionomycin. The 1,25(OH)(2)D(3)-induced
      sustained increase in [Ca(2+)](i) in breast cancer cells was associated with
      induction of apoptotic cell death, whereas the transient [Ca(2+)](i) increase in
      normal cells was not. The forced expression of calbindin-D(28k) in cytosol or
      increase in the cytosolic Ca(2+) buffering capacity with the cell-permeant Ca(2+)
      buffer BAPTA prevented induction of apoptosis with 1,25(OH)(2)D(3) in cancer
      cells. The sustained increase in [Ca(2+)](i) in breast cancer cells was
      associated with activation of the Ca(2+)-dependent apoptotic proteases, mu
      calpain and caspase-12, as evaluated with antibodies to active (cleaved) forms of
      the enzymes and the fluorogenic peptide substrates. Selective inhibition of the
      Ca(2+) binding sites of mu-calpain decreased apoptotic indices in the cancer
      cells treated with 1,25(OH)(2)D(3), thapsigargin, or ionomycin. The mu-calpain
      activation preceded expression/activation of caspase-12, and calpain was required
      for activation/cleavage of caspase-12. Certain non-calcemic vitamin D analogs
      (e.g., EB 1089) triggered a sustained [Ca(2+)](i) increase, activated Ca(2+)
      dependent apoptotic proteases, and induced apoptosis in breast cancer cells in a
      fashion similar to that of 1,25(OH)(2)D(3). The 1,25(OH)(2)D(3)-induced transient
      Ca(2+) response in normal mammary epithelial cells was not accompanied by
      activation of mu-calpain and caspase-12. In conclusion, we have identified the
      novel apoptotic pathway in breast carcinoma cells treated with 1,25(OH)(2)D(3):
      increase in [Ca(2+)](i)-->mu-calpain activation-->caspase-12 activation-
      >apoptosis. Our results support the hypothesis that 1,25(OH)(2)D(3) directly
      activates this apoptotic pathway by inducing a sustained increase in [Ca(2+)](i).
      Differences of Ca(2+) regulatory mechanisms in cancer versus normal cells seem to
      allow 1,25(OH)(2)D(3) and vitamin D analogs to induce Ca(2+)-mediated apoptosis
      selectively in breast cancer cells. Thus, deltanoids may prove to be useful in
      the treatment of tumors susceptible to induction of Ca(2+)-mediated apoptosis.

PMID- 16081285
TI  - Regulation of utrophin in transgenic mice.

PMID- 16081287
TI  - The significance of mammotome core biopsy specimens without radiographically
      identifiable microcalcification and their influence on surgical management--a
      retrospective review with histological correlation.
AB  - The aim of this study is to assess core specimens which do not contain
      radiographically visible calcification at stereotactic vacuum assisted core
      biopsy (SVACB) of indeterminate microcalcification, to determine what influence
      they may have on the surgical management of patients with breast disease. Review
      was made of the core biopsy and surgical histology results of 104 SVACB biopsies
      of indeterminate microcalcification over a 26 month period. Cores were placed in
      separate pots; POT A for cores containing microcalcification and POT B for cores
      without radiographically visible microcalcification before being sent to
      histology. Of 104 biopsies, 25% contained B3-B5 pathology in POT B and at surgery
      this correlated with a higher grade of ductal carcinoma in situ (DCIS) and an
      increased likelihood of invasive disease. The presence of B3-B5 pathology in POT
      B itself however did not act as a strong indicator of radiological-histological
      size discrepancy in this study.

PMID- 16081288
TI  - Long-term survival in pituitary metastasis from breast cancer.
AB  - We report the interesting case of a patient who is a long-term survivor of breast
      cancer with metastasis to the pituitary gland. This patient was treated with
      surgery and radiotherapy in 1995 and during her second relapse, which occurred in
      2004, chemotherapy was given. This treatment resulted in a partial response.

PMID- 16081289
TI  - A 13-year follow-up of patients with breast cancer presenting to a District
      General Hospital breast unit in southeast England.
AB  - The purpose of this clinical cohort study was to examine long-term survival in
      groups of screen-detected and symptomatic breast cancer patients attending a
      specialist breast unit, and to determine the factors affecting this survival. A
      total of 3239 breast cancer cases (1252 screen-detected and 1987 symptomatic)
      diagnosed between 1989 and 2002 were followed up until the end of 2002, and
      breast cancer-specific survival was examined in the screened and symptomatic
      groups, in relation to patient age, tumour size, nodal status and histological
      grade. Long-term survival in this clinical cohort was high. Relative survival
      values in the symptomatic group were similar to population-based estimates for
      southeast England derived from data held at the Thames Cancer Registry, whilst
      survival values in the screening group were 11-12 percentage points higher at 4
      years after diagnosis and onwards. Ten-year relative survival estimates were 88%
      in the screening group and 77% in symptomatic cases. In groups of comparable age,
      the difference in breast cancer-specific survival at 10 years was 19 percentage
      points. Survival was significantly related to tumour characteristics (size, nodal
      status and grade), but not to morphological tumour type or deprivation score of
      the subject. After adjustment for other factors, the difference in survival
      between the two groups was much attenuated and became statistically non
      significant. The higher survival seen in the screening group can be almost
      entirely accounted for in terms of the detection of early stage and lower grade
      tumours which screening provides.

PMID- 16081290
TI  - The effects of tamoxifen on radiation-induced pulmonary fibrosis in Wistar albino
      rats: results of an experimental study.
AB  - This study was performed to evaluate the effects of tamoxifen on pulmonary
      fibrosis, given concurrently with or after irradiation in Wistar albino rats.
      Twenty-one female Wistar albino rats were randomized into three groups. The first
      group (Group A) had tamoxifen, which was started after the completion of
      irradiation. The second group (Group B) had tamoxifen concomitant with
      irradiation. The third group (Group C) had only thoracic irradiation and did not
      receive tamoxifen. Whole lungs were irradiated to a total dose of 30Gy in ten
      fractions with Co60. Tamoxifen was continued until the animals were sacrificed 16
      weeks after the start of irradiation. As an end point the percentage of lung with
      fibrosis for each rat was quantified with image analysis of histological sections
      of the lung. Groups were compared using the one-way ANOVA method and Bonferroni
      post hoc test. The mean percentage values of fibrosis were 10.03 for Group A,
      36.81 for Group B, and 3.87 for group C (P<0.001). When the percentages of
      fibrosis were compared for each group, the difference was statistically
      significant between Group A and Group B (P<0.001) and between Group B and Group C
      (P<0.001). Concomitant use of tamoxifen appears to increase radiation-induced
      pulmonary fibrosis and it seems more convenient to delay tamoxifen until the
      completion of irradiation.

PMID- 16081291
TI  - A QSAR review on melanoma toxicity.
AB  - Melanoma is one of the most aggressive forms of skin cancer and is currently
      attracting our attention particularly in the area of quantitative structure
      activity relationships (QSAR). In the present review, an attempt has been made to
      collect the data for different sets of compounds and to discuss their toxicities
      toward melanoma cells by the formulation of a total number of 36 QSAR.

PMID- 16081292
TI  - Selective anti-tubercular purines: synthesis and chemotherapeutic properties of 6
      aryl- and 6-heteroaryl-9-benzylpurines.
AB  - 6-Aryl- and 6-heteroaryl-9-benzylpurines have been synthesized employing
      palladium-catalyzed coupling reactions in the step forming the C-C or C-N bond
      between the aryl- or heteroaryl and the purine. The compounds were screened for
      activity against Mycobacterium tuberculosis as well as representative Gram+ and
      Gram- bacteria, and for cytotoxic effects on mammalian cells. Several potent
      antimycobacterials were identified. These compounds probably act by a novel and
      selective mechanism; they exhibit low toxicity toward other bacteria as well as
      mammalian cells.

PMID- 16081293
TI  - 8-O-Azeloyl-14-benzoylaconine: a new alkaloid from the roots of Aconitum
      karacolicum Rapcs and its antiproliferative activities.
AB  - A new alkaloid of Aconitum karacolicum Rapcs, from the Ranunculaceae family,
      collected in Kirghizstan, was isolated from the roots of this plant, using a
      purification scheme based upon its in vitro antiproliferative properties against
      three human tumour cell lines in culture. Structural identification was performed
      using high resolution MS-MS mass spectrometry and (1)H, (13)C, 2D NOESY NMR
      spectroscopy analysis. This compound consists of a 14-benzoylaconine moiety
      substituted on C-8 by an azeloyl chain. It presents in vitro cytotoxicity with an
      IC(50) of about 10-20 microM, which warrants further investigation on its
      possible interest in cancer chemotherapy.

PMID- 16081294
TI  - Identification and characterization of small molecule modulators of KChIP/Kv4
      function.
AB  - Potassium channels and their associated subunits are important contributors to
      electrical excitability in many cell types. In this study, a yeast two-hybrid
      assay was used to identify inhibitors such as a diaryl-urea compound (CL-888)
      that binds to and modulates the formation of the Kv4/KChIP complex. CL-888
      altered the apparent affinity of KChIP1 to Kv4.3-N in a Biacore assay, but did
      not dissociate the two proteins in size-exclusion chromatography experiments.
      Kv4.2/KChIP1 current amplitude and kinetics were altered with compound exposure,
      supporting the hypothesis of a compound-induced conformational change in the
      protein complex. Fluorescence spectroscopy of a unique tryptophan residue in
      KChIP1 was consistent with compound binding to the protein. Molecular modeling
      using the KChIP1 crystal structure indicates that compound binding may occur in a
      small tryptophan-containing binding pocket located on the hydrophilic side of the
      protein.

PMID- 16081295
TI  - Synthesis and antileishmanial activities of 4,5-di-substituted acridines as
      compared to their 4-mono-substituted homologues.
AB  - Newly synthesized 4,5-di-substituted acridines were assessed for in vitro
      antileishmanial activities as compared to those of their 4-mono-substituted
      homologues. Mono-substituted acridines exhibited a weak specificity for
      Leishmania parasites. Di-substituted acridines, on the contrary, displayed
      interesting amastigote-specific activities through a mechanism of action that
      might not involve intercalation to DNA. This antileishmanial property, associated
      with a low antiproliferative activity towards human cells, led to the
      identification of a new class of promising acridine derivatives such as 4,5
      bis(hydroxymethyl)acridine with a nonclassical mechanism of action based on the
      inhibition of Leishmania internalization within macrophages. In the meantime, the
      effects of experimental lighting on the biological properties of acridines were
      assessed: experimental lighting did not significantly improve the antileishmanial
      activity of the compounds since it produced a greater toxicity against human
      cells.

PMID- 16081296
TI  - Characterizing the topography of membrane receptors and signaling molecules from
      spatial patterns obtained using nanometer-scale electron-dense probes and
      electron microscopy.
AB  - The flow of information through a cell requires the constant remodeling of cell
      signaling networks. Thus, spatially and temporally resolved microscopy of
      signaling components is needed to understand the behavior of normal cells as well
      as to uncover abnormal behavior leading to human disease. Nanoprobe labeling and
      transmission electron microscopy of cytoplasmic face-up sheets of cell membrane
      have been developed as a high-resolution approach to map the interactions of
      proteins and lipid during cell signaling. Membrane sheets are labeled with 3-15
      nm electron-dense probes for receptors, signaling proteins and lipids and
      micrographs record the distributions of the probes relative to each other and to
      surface features. Here, we establish computational methods to extract spatial
      coordinates of probes from micrographs, to analyze and statistically validate the
      clustering and co-clustering of these probes and to integrate results between
      experiments in order to establish the relative spatial distributions of single
      and multiple probes. Our analyses, and the resulting programs for automating data
      collection and for carrying out statistical and clustering analyses provide
      toolboxes specialized for the spatiotemporal analysis and modeling of signal
      transduction pathways.

PMID- 16081297
TI  - The extracellular matrix of the human aortic wall: ultrastructural observations
      by FEG-SEM and by tapping-mode AFM.
AB  - Fragments of human ascending aorta harvested during heart surgery were
      cryofractured and observed by scanning electron microscopy (SEM) and atomic force
      microscopy (AFM). Elastic fibers appear as irregular, undulated laminae of
      variable size and shape. Their surface shows an evident fibrous texture
      suggestive of a criss-crossed, delicate filamentous scaffold and is marked by a
      number of features such as ridges, holes and protruding ribs. At higher
      magnification, both SEM and AFM show the surface composed of a finely granular
      material, with a bead size of approximately 20 nm. However, the thickness of the
      metal coating in one case, and the tip convolution effect on the other, may
      equally result in an artifactual enlargement of the structures, so that the beads
      may be significantly smaller. The surfaces created by the fracture always appear
      smooth and compact and with this technique do not reveal significant detail. The
      collagen component is mostly represented by small, uniform fibrils gathered in
      flexuous bundles and following a wavy course not unlike that of the elastic
      laminae. An orthogonal lattice of small proteoglycans is readily evident even
      without a specific treatment. Occasionally, the fibrils appear encrusted or
      engulfed in a grainy matrix reminiscent of the elastic fiber surface. Fluid
      Tapping-Mode Atomic Force Microscopy simultaneously reveals the surface-bound
      proteoglycans and the inner architecture of the fibrils, composed of smaller
      subunits following a spiral course with a winding angle of approximately 17
      degrees.

PMID- 16081298
TI  - Monte Carlo assessment of soil moisture effect on high-energy thermal neutron
      capture gamma-ray by 14N.
AB  - Among many conventional techniques, nuclear techniques have shown to be faster,
      more reliable, and more effective in detecting explosives. In the present work,
      neutrons from a 5 Ci Am-Be neutron source being in water tank are captured by
      elements of soil and landmine (TNT), namely (14)N, H, C, and O. The prompt
      capture gamma-ray spectrum taken by a NaI (Tl) scintillation detector indicates
      the characteristic photo peaks of the elements in soil and landmine. In the high
      energy region of the gamma-ray spectrum, besides 10.829 MeV of (15)N, single
      escape (SE) and double escape (DE) peaks are unmistakable photo peaks, which make
      the detection of concealed explosive possible. The soil has the property of
      moderating neutrons as well as diffusing the thermal neutron flux. Among many
      elements in soil, silicon is more abundant and (29)Si emits 10.607 MeV prompt
      capture gamma-ray, which makes 10.829 MeV detection difficult. The Monte Carlo
      simulation was used to adjust source-target-detector distances and soil moisture
      content to yield the best result. Therefore, we applied MCNP4C for configuration
      very close to reality of a hidden landmine in soil.

PMID- 16081299
TI  - Impact of inhibition of Qo site of mitochondrial complex III with myxothiazol on
      persistent sodium currents via superoxide and protein kinase C in rat hippocampal
      CA1 cells.
AB  - Inhibition of Qo site of mitochondrial complex III under hypoxia has received
      attention, but its downstream pathways remain unclear. We used Qo site inhibitor
      myxothiazol to mimic the inhibition of the Qo site of complex III and studied the
      effects of the inhibition of this site on persistent and transient sodium
      currents and neuron excitability in rat hippocampal CA1 cells. The results showed
      myxothiazol apparently increased persistent sodium currents but with a weak
      effect on transient sodium currents; the effect of myxothiazol on persistent
      sodium currents was blocked by protein kinase C inhibitor and superoxide
      scavengers, but not by hydrogen peroxide scavenger and hydroxyl radical formation
      inhibitor; myxothiazol could increase the activity of protein kinase C and neuron
      excitability. These results suggest that the inhibition of Qo site of
      mitochondrial complex III increases persistent sodium currents via superoxide
      production and protein kinase C activation.

PMID- 16081300
TI  - Derivation of neural precursors from human embryonic stem cells in the presence
      of noggin.
AB  - The utilization of human embryonic stem cells (hESC) for basic and applied
      research is hampered by limitations in directing their differentiation. Empirical
      poorly defined methods are currently used to develop cultures enriched for
      distinct cell types. Here, we report the derivation of neural precursors (NPs)
      from hESC in a defined culture system that includes the bone morphogenetic
      protein antagonist noggin. When hESC are cultured as floating aggregates in
      defined medium and BMP signaling is repressed by noggin, non-neural
      differentiation is suppressed, and the cell aggregates develop into spheres
      highly enriched for proliferating NPs. The NPs can differentiate into astrocytes,
      oligodendrocytes, and mature electrophysiologically functional neurons. During
      prolonged propagation, the differentiation potential of the NPs shifts from
      neuronal to glial fate. The presented noggin-dependent controlled conversion of
      hESC into NPs is valuable for the study of human neurogenesis, the development of
      new drugs, and is an important step towards the potential utilization of hESC in
      neural transplantation therapy.

PMID- 16081301
TI  - Evaluation of Brucella abortus S19 vaccine strains by bacteriological tests,
      molecular analysis of ery loci and virulence in BALB/c mice.
AB  - Two Brucella abortus S19 commercial vaccine strains used for vaccination against
      brucellosis in India and three S19 strains available as international reference
      were examined by microbiological assays and molecular analysis of the ery loci
      involved in erythritol metabolism, and tested for residual virulence in BALB/c
      mice. According to the sensitivity to penicillin and i-erythritol, the five
      strains tested had the phenotypic characteristics of strain S19. However, on
      culture medium containing i-erythritol, all strains developed spontaneous i
      erythritol resistant colonies at mutation rates ranging from 1.42x10(-2) to
      1.33x10(-6). The S19 characteristic 702 bp deletion in the erythrulose 1
      phosphate dehydrogenase gene of the ery locus was present only in the three
      reference strains but not in the two commercial vaccines. Both commercial strains
      and one of the reference strains showed reduced virulence in BALB/c mice. The
      presence or absence in S19 strains of the 702 bp deletion in the ery locus had no
      correlation with either the rates of spontaneous mutation to erythritol
      resistance or the residual virulence in mice.

PMID- 16081302
TI  - Frequency-correlated decreases of motor cortex activity associated with
      subthalamic nucleus stimulation in Parkinson's disease.
AB  - According to the classical model of basal ganglia organization, deep brain
      stimulation (DBS) in the subthalamic nucleus (STN) for the treatment of
      Parkinson's disease (PD) blocks overactive excitatory projections to inhibitory
      basal ganglia output structures. This would release the break on thalamofrontal
      neurons alleviating the poverty of movement, the hallmark of PD. Such parallels
      to a functional lesion certainly simplify the mechanism of STN DBS. Here, we
      applied parametric analyses of H2(15)O positron emission tomography (PET) scans
      at rest while systematically varying stimulation frequency in 6 patients with STN
      DBS for akinetic PD. A strong positive correlation of rCBF to increasing
      stimulation frequency was detected around the STN bilaterally. More importantly,
      we show that gradual increases in STN stimulation frequency are tightly
      correlated with decreases in motor cortex activity. This demonstrates an active
      modulation of resting activity within the subcortical stimulation target and
      within motor cortex by STN DBS. Rather than a possible downstream effect, we
      propose to consider the tight correlations between DBS frequency and motor cortex
      activity in the context of an upstream modulation of direct efferents to the STN
      from primary motor and premotor cortices.

PMID- 16081303
TI  - Distinct amygdala-autonomic arousal profiles in response to fear signals in
      healthy males and females.
AB  - The amygdala has a key role in regulating arousal and vigilance, and responds to
      both visual and vocal signals of fear, including facial expressions of fear. In
      this study, we used functional MRI to examine sex differences in the magnitude,
      extent, lateralization and time course of amygdala responses to facial signals of
      fear, in a relatively large sample of males and females. Skin conductance was
      recorded simultaneously with functional imaging to examine concomitant changes in
      emotional arousal, and to provide an independent index of response attenuation.
      Scanning and skin conductance recording was undertaken during perception of
      facial fear stimuli. Sex differences were apparent in the laterality and time
      course of fear perception. In males, the right amygdala and autonomic arousal
      attenuated over the late half of the experiment. By contrast, females showed
      persistent bilateral amygdala responses, with a tendency towards greater left
      amygdala engagement during the late phase. Females also showed a greater general
      extent of amygdala response. We suggest that distinct evolutionary pressures
      might contribute to a lower threshold for vigilance to signals of danger in
      females, reflected in a profile of sustained amygdala-arousal interaction.

PMID- 16081304
TI  - Reexamination of the Iberian and North African Podarcis (Squamata: Lacertidae)
      phylogeny based on increased mitochondrial DNA sequencing.

PMID- 16081305
TI  - Ischaemic skeletal muscle increases serum ischaemia modified albumin.
AB  - OBJECTIVES: Ischaemia modified albumin (IMA) has been used as a marker of
      myocardial ischaemia but little is known about its production during ischaemia of
      other tissues. The clinical models of patients with intermittent claudication and
      major arterial surgery were used to investigate IMA production from ischaemic
      skeletal muscle. DESIGN: Prospective clinical study. MATERIALS AND METHODS: IMA
      was measured pre-operatively, at end ischaemia, and 5 min, 4, 24, 48, 72 and 144
      h post-surgery in patients undergoing (a) revascularisation for intermittent
      claudication (IC, n=15), (b) abdominal aortic aneurysm repair (AAA, n=12) and
      controls (n=16). RESULTS: The median pre-operative IMA concentration in IC
      patients was significantly higher than the AAA group (88.3 versus 83.5 U/ml,
      p=0.036) and controls (88.3 versus 80.3 U/ml, p=0.031). IMA concentrations
      increased significantly during arterial clamping in both IC and AAA groups (88.3
      versus 120.0 U/ml, p=0.001; 83.5 versus 118.8 U/ml, p=0.002, respectively)
      consistent with increased skeletal muscle ischaemia. In contrast, there was only
      a mild perioperative increase in the controls (80.3 versus 91.6 U/ml, p=0.012).
      CONCLUSIONS: Patients with intermittent claudication have significantly elevated
      IMA and skeletal muscle ischaemia during arterial surgery results in
      significantly increased circulating IMA. When IMA is used to detect myocardial
      ischaemia, ischaemic skeletal muscle must be excluded.

PMID- 16081306
TI  - Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis.
AB  - Tumor-derived immune suppression is considered to be a major mechanism of tumor
      evasion from the immune system destruction, however, little is known regarding
      the induction of T-cell functional suppression by tumor-derived exosomes. Herein,
      we investigate tumor-derived exosomes involved in normal immunological
      communications as means of inhibiting an antitumor T-cell response. Exosomes
      derived from LNCaP, a human prostate cancer cell line, were visualized by FACS
      and identified based on size (80-200 nm) in comparison to marker beads. Exosomes
      from tumor cell line inhibited T-cell proliferation. Dose-dependent apoptosis of
      T cells was induced by co-culture with tumor exosomes. Addition of anti-FasL
      antibody blocked the apoptosis induction by tumor exosomes. This study suggests
      that induction of T-cell apoptosis by tumor-derived exosomes appears to be a
      novel mechanism of tumor immune evasion.

PMID- 16081307
TI  - Studying the S-nitrosylation of model peptides and eNOS protein by mass
      spectrometry.
AB  - Oxidative addition of a nitric oxide (NO) molecule to the thiol group of cysteine
      residues is a physiologically important post-translational modification that has
      been implicated in several metabolic and pathophysiological events. Our previous
      studies have indicated that S-nitrosylation can result in the disruption of the
      endothelial NO synthase (eNOS) dimer. It has been suggested that for S
      nitrosylation to occur, the cysteine residue must be flanked by hydrophilic
      residues either in the primary structure or in the spatial proximity through
      appropriate conformation. However, this hypothesis has not been confirmed. Thus,
      the objective of this study was to determine if the nature of the amino acid
      residues that flank the cysteine in the primary structure has a significant
      effect on the rate and/or specificity of S-nitrosylation. To accomplish this, we
      utilized several model peptides based on the eNOS protein sequence. Some of these
      peptides contained point mutations to allow for different combinations of amino
      acid properties (acidic, basic, and hydrophobic) around the cysteine residue. To
      ensure that the results obtained were not dependent on the nitrosylation
      procedure, several common S-nitrosylation techniques were used and S
      nitrosylation followed by mass spectrometric detection. Our data indicated that
      all peptides independent of the amino acids surrounding the cysteine residue
      underwent rapid S-nitrosylation. Thus, there does not appear to be a profound
      effect of the primary sequence of adjacent amino acid residues on the rate of
      cysteine S-nitrosylation at least at the peptide levels. Finally, our studies
      using recombinant human eNOS confirm that Cys98 undergoes S-nitrosylation. Thus,
      our data validate the importance of Cys98 in regulating eNOS dimerization and
      activity, and the utility of mass spectroscopy to identify cysteine residues
      susceptible to S-nitrosoylation.

PMID- 16081308
TI  - Structure determination of aligned systems by solid-state NMR magic angle
      spinning methods.
AB  - Single crystal rotational echo double resonance (REDOR) experiments can be used
      to determine the three-dimensional orientation of heteronuclear bond vectors in
      an amino acid, as well as the crystal's orientation relative to the rotor fixed
      frame (RFF). We also demonstrate that for samples uniaxially aligned along the
      rotor axis, the polar tilt angle of a bond vector relative to the RFF can be
      measured by use of an analytical expression that describes the REDOR curve for
      that system. These bond orientations were verified by X-ray indexing of the
      single crystal sample, and were shown to be as accurate as +/- 1 degrees .

PMID- 16081309
TI  - Expression and tissue distribution of astacin-like squid metalloprotease (ALSM).
AB  - Astacin metalloprotease family members function in a wide variety of biologic
      events, including cell differentiation and morphogenesis during embryonic
      development and adult tissue differentiation. We previously isolated and
      characterized an astacin-like squid metalloprotease (ALSM). To elucidate the
      embryonic expression of ALSM, we performed immunohistochemical analysis with
      specific antibodies and examined the expression profiles of ALSM isoforms by in
      situ hybridization analysis. Tissue distribution and expression were also
      examined in adult spear squid. mRNA expression of ALSM isoforms I and III was
      first detected in newly hatched squid and was restricted to the liver. No mRNA
      signals were detected in other tissues even in adult squids. At the protein
      level, both isoforms were prominent in the liver of embryos and later in
      digestive organs of adult squid. Both isoforms were also detected in muscle
      tissues, including mantle and tentacle muscle. Staining for ALSM III was also
      identified in the iris and in tissues near the eye in squid embryos. However, no
      reactive bands were detected by immunoblotting of adult squid eyes. Thus, ALSM is
      initially expressed at the late stage of embryogenesis in spear squid, and
      expression is restricted to the liver. Thereafter, ALSM isoforms function in
      various tissues in an isoform-dependent manner.

PMID- 16081310
TI  - Phenotypic heterogeneity in the presentation of D-2-hydroxyglutaric aciduria in
      monozygotic twins.
AB  - D-2-hydroxyglutaric aciduria (D-2-HGA) is a very rare autosomal recessive
      metabolic disorder that has recently been associated with mutations in the D-2
      hydroxyglutarate dehydrogenase gene. The biochemical phenotype of D-2-HGA is
      defined by the accumulation of abnormal amounts of D-2-hydroxyglutarate in
      cerebrospinal fluid, blood, and urine while the clinical phenotype can vary from
      a severe epileptic encephalopathy to normal. The basis for this phenotypic
      variation is not well-defined. We report a set of 412-year-old monozygotic (MZ)
      female twins with D-2-hydroxyglutaric aciduria who are shown to be compound
      heterozygotes for c.326-327dupTC, p.Glu110ArgfsX19, and c.1123G-->T, p.Asp375Tyr
      mutations in the D-2-hydroxyglutarate dehydrogenase gene, but who have remarkably
      different clinical phenotypes. One twin presented with multiple congenital
      anomalies, severe developmental delay, and abnormal neuroradiological findings,
      while the other had normal neurocognitive and neuroradiological phenotypes,
      without concomitant congenital abnormalities. Monozygosity of these twins implies
      that the differences in the clinical phenotype arise from postzygotic genetic
      changes, epigenetic differences, or environmental factors that influence the
      phenotypic response to biochemical perturbation rather than allelic or locus
      heterogeneity. Though the mechanistic role of these factors in D-2-HGA is far
      from apparent, the discordance in the phenotypes of these siblings establishes
      that these factors are at least as important as the nature of the mutant alleles
      in influencing the progression of the disorder.

PMID- 16081311
TI  - The psychophysics of glaucoma: improving the structure/function relationship.
AB  - Perimetry of some kind remains an important tool in the detection, diagnosis and
      monitoring of glaucomatous damage to the visual pathway. However, recent studies
      have served to reinforce the suspicion that conventional perimetry does not
      possess the sensitivity to detect the earliest signs of functional loss resulting
      from glaucoma. The relationship between differential light threshold and ganglion
      cell loss is extremely weak and, in the early stages of glaucoma, non-existent.
      Alternative, more novel perimetric techniques seem to offer promise of better
      detectability for early loss by claiming to tap in to one or other of the
      separate parallel pathways of the visual system. While some of these tests show
      potential for better detection and monitoring of glaucoma, the reasons why this
      might be so are not always clearly formulated or represented. This leads to
      misunderstanding of what the test actually measures and of the glaucomatous
      disease process itself. This paper seeks to revisit and review the theory
      underlying psychophysical testing of visual function related to glaucoma and
      stresses the importance of developing tests that are based on a firm theoretical
      understanding of visual function and processing in order to both detect glaucoma
      at an earlier stage and better understand the mechanisms of loss from the disease
      process.

PMID- 16081312
TI  - Gene-expression analysis and network discovery using Genevestigator.
AB  - The Genevestigator software suite belongs to a new generation of web-based tools
      that provide categorized quantitative information about elements (genes or
      annotations) contained in large microarray databases. The first version of
      Genevestigator, in use since 2004, has now been updated to enable faster, more
      powerful and more diverse types of queries for gene-function analysis and network
      discovery.

PMID- 16081313
TI  - Symmetry perception in humans and macaques.
AB  - The human ability to detect symmetry has been a topic of interest to
      psychologists and philosophers since the 19th century, yet surprisingly little is
      known about the neural basis of symmetry perception. In a recent fMRI study,
      Sasaki and colleagues begin to remedy this situation. By identifying the neural
      structures that respond to symmetry in both humans and macaques, the authors lay
      the groundwork for understanding the neural mechanisms underlying symmetry
      perception.

PMID- 16081314
TI  - Review of prevalence of Simian Virus 40 (SV40) genomic infection in healthy
      subjects.
AB  - Because of the carcinogenicity of SV40 in rodents, and its possible distribution
      through the polio vaccine, many studies have been conducted to determine if there
      is an association between SV40 genomic infection and different types of cancer;
      sometimes, these studies included data on the prevalence of genomic infection in
      healthy subjects as secondary information. We reviewed all the studies that
      reported the prevalence of SV40 genomic infection in healthy subjects, tested by
      PCR based methods. The 20 articles considered here included 1103 samples from
      healthy subjects, with a prevalence of infection ranging from 0 to 25.6%, with
      high heterogeneity, and no association with the type of sample analyzed (Mantel
      Haenszel OR: 0.74; 95% CI: 0.44-1.23). The wide variation in frequency pose
      problems in terms of study design; in fact, the representativeness of the samples
      used as controls in the published studies may be very limited. Larger studies on
      healthy subjects, tested for SV40 genomic infection at various genomic regions,
      conducted in different geographic areas, are needed.

PMID- 16081315
TI  - Detailed review of transgenic rodent mutation assays.
AB  - Induced chromosomal and gene mutations play a role in carcinogenesis and may be
      involved in the production of birth defects and other disease conditions. While
      it is widely accepted that in vivo mutation assays are more relevant to the human
      condition than are in vitro assays, our ability to evaluate mutagenesis in vivo
      in a broad range of tissues has historically been quite limited. The development
      of transgenic rodent (TGR) mutation models has given us the ability to detect,
      quantify, and sequence mutations in a range of somatic and germ cells. This
      document provides a comprehensive review of the TGR mutation assay literature and
      assesses the potential use of these assays in a regulatory context. The
      information is arranged as follows. (1) TGR mutagenicity models and their use for
      the analysis of gene and chromosomal mutation are fully described. (2) The
      principles underlying current OECD tests for the assessment of genotoxicity in
      vitro and in vivo, and also nontransgenic assays available for assessment of gene
      mutation, are described. (3) All available information pertaining to the conduct
      of TGR assays and important parameters of assay performance have been tabulated
      and analyzed. (4) The performance of TGR assays, both in isolation and as part of
      a battery of in vitro and in vivo short-term genotoxicity tests, in predicting
      carcinogenicity is described. (5) Recommendations are made regarding the
      experimental parameters for TGR assays, and the use of TGR assays in a regulatory
      context.

PMID- 16081316
TI  - Skill needs for nurses in their role as health informatics professionals: a
      survey in the context of global health informatics education.
AB  - In the process of developing global health informatics education, a common
      understanding of educational outcomes is required. Therefore, an educational
      framework for health informatics professionals is desirable to support student
      mobility, trans-national and borderless education. Nurses form a significant part
      of the health workforce and need to be properly educated for their roles in
      health informatics. To ascertain their perceptions of needs and priorities, we
      developed a web-based questionnaire and surveyed Australian nurses on the
      preferred knowledge/skills set for health informatics professionals. Among
      others, the questionnaire is based on the International Medical Informatics
      Association's (IMIA) set of recommendations on education and IMIA's scientific
      map. Benner's five levels of competencies were applied to measure the degree of
      competency required for each skill/knowledge. Altogether, 82 Australian nurses
      completed the questionnaire. The nurses' perceived degree of competency required
      for a total of 74 specific skills and knowledge in five skill categories is
      presented in this paper as well as the overall results for each of the five
      categories. Further, significant differences between the nurses' primary roles
      and primary interest in health informatics are discussed. The development of a
      comprehensive health informatics education framework needs to take into account
      nurses as well as other health professionals. Repeating the survey in other
      countries and for various professions is essential to develop an international
      educational framework.

PMID- 16081317
TI  - The 5-lipoxygenase pathway in arterial wall biology and atherosclerosis.
AB  - Leukotrienes (LTs) are powerful inflammatory lipid mediators derived from the 5
      lipoxygenase (5-LO) cascade of arachidonic acid. Recent clinical, population
      genetic, cell biological, and mouse studies indicate participation of the 5-LO
      pathway in atherogenesis and arterial wall remodeling. 5-LO is expressed by
      leukocytes including blood monocytes, tissue macrophages, dendritic cells,
      neutrophils, and mast cells. LTB4 and the cysteinyl LTs LTC4, LTD4, and LTE4, act
      through two BLT and two cysLT receptors that are differentially expressed on
      hematopoietic and arterial wall cells. The precise roles of LTs or the LT
      receptors in cardiovascular physiology remain largely to be explored. In this
      review, we will discuss what is currently known about the 5-LO atherosclerosis
      connection. We will attempt to propose strategies to further explore potential
      links between the 5-LO pathway and blood vessel physiology and disease
      progression.

PMID- 16081319
TI  - The impact of morbid events on survival following hospitalization for complicated
      myocardial infarction.
AB  - BACKGROUND: Little is known about the importance of morbid events with respect to
      longer term survival following MI hospital discharge. AIMS: Establish the risk of
      death associated with morbid events following initial discharge from MI
      hospitalization. METHODS: We examined the rates of morbid events (reinfarction,
      stroke/TIA, revascularization, heart failure (HF) hospitalization, cardiovascular
      hospitalization and all-cause hospitalization) and the relationships of these
      events to subsequent death in patients who survived the initial hospitalization
      for MI (n = 5301) in the OPTIMAAL trial. Events were classified as Early (< or =
      30 days post discharge) and Late (> 30 days post discharge) for an average of 2.7
      years follow-up. RESULTS: Death rates were higher in the Early period (0.20
      deaths/patient year) than in the Late period (0.05 deaths/patient year). Once a
      morbid event, excluding revascularization, occurred, the acute hazard ratios (HR,
      determined by Cox regression) for death on the day of event were higher than at
      time periods following the event and were highest for reinfarction and
      stroke/TIA. The acute HRs for death for all 6 morbid events were especially high
      for events occurring during the Late period. The highest chronic HR for death was
      associated with HF and all-cause hospitalizations. By contrast, the chronic HR
      for death from revascularization in both the Early (HR = 0.3) and Late (HR = 0.4)
      period indicated reduced risk. CONCLUSIONS: The results document event rates
      following hospitalization for MI, provide quantification of the associated risk
      for death, and may be useful in designing clinical trials. The serious morbid
      events examined may serve as potential surrogate endpoints in long-term studies
      and identify patients that should be targeted for aggressive management.

PMID- 16081318
TI  - Does symptom-limited cycle exercise cause low frequency diaphragm fatigue in
      patients with heart failure?
AB  - BACKGROUND: Reduced diaphragm contractility occurs in some healthy subjects when
      they exercise to exhaustion. This indicates low frequency fatigue, which may
      contribute to task failure. We hypothesised that patients with congestive heart
      failure (CHF) might be especially vulnerable to the development of low frequency
      diaphragm fatigue after exhaustive exercise. AIMS: To study the effect of
      exhaustive incremental cycle exercise on diaphragm contractility in patients with
      CHF. METHODS: 12 patients with CHF with an ejection fraction of 36.5 +/- 7.3% and
      12 healthy age-matched control subjects performed an incremental cycle test to
      exhaustion. The unpotentiated twitch transdiaphragmatic pressure (twitch Pdi) in
      response to bilateral anterolateral magnetic phrenic nerve stimulation (BAMPS)
      was measured before and after exercise. RESULTS: Twitch Pdi at baseline was 20.2
      +/- 6.7 cm H2O in the CHF group and 20.3 +/- .3 cm H2O in the controls (p =
      0.957). 25 and 35 min post exercise the values were 19.9+/-5.4 and 20.0+/-5.1 cm
      H2O in the CHF group and 20.6 +/- 4.3 and 21.2 +/- 3.4 cm H2O in the control
      group; neither change was significant (F(2,27) = 0.007, p = 0.993; F(2,33) =
      0.144, p = 0.866, respectively). CONCLUSION: When patients with CHF cycle to
      exhaustion, low frequency fatigue of the diaphragm does not occur, and this is
      unlikely to be an important factor limiting exercise capacity of such patients.

PMID- 16081320
TI  - 2-5A antisense treatment of respiratory syncytial virus.
AB  - Although a prominent cause of upper and lower respiratory tract disease in
      infants and the elderly, clinical options for treatment of respiratory syncytial
      virus (RSV) infections remain limited. Historically, attempts to develop vaccines
      have been unsuccessful, and rapid viral mutation rates have stifled development
      of several small molecule-based antiviral agents. Thus, targeted approaches to
      block RSV replication, including humanized monoclonal antibodies and nucleic acid
      based strategies (antisense and RNA interference), have emerged as potentially
      viable drug development options.

PMID- 16081321
TI  - TRIM5alpharh expression restricts HIV-1 infection in lentiviral vector-transduced
      CD34+-cell-derived macrophages.
AB  - Species-specific innate resistance against viral infections offers novel avenues
      for antiviral therapeutic and prophylactic approaches. The retroviral and
      lentiviral restriction factors Ref1 and Lv1 are variants of the tripartite motif
      protein TRIM5alpha, a component of cytoplasmic bodies. TRIM5alpha severely
      restricts productive retroviral infections at the postentry and preintegration
      steps by destabilizing the incoming viral capsid via ubiquitination. Using this
      approach, resistance to HIV-1 infection could be conferred by TRIM5alpha(rh)
      expression in otherwise susceptible cells. Here we show that stable expression of
      simian TRIM5alpha(rh) via a lentiviral vector in a permissive cell culture line,
      Magi-CXCR4, conferred resistance to HIV-1. To translate these findings into a
      stem cell gene therapy setting, the TRIM5alpha(rh) transgene was stably
      introduced into CD34(+) hematopoietic progenitor cells to derive transgenic
      macrophages. Upon viral challenge, TRIM5alpha(rh)-expressing macrophages were
      highly resistant to HIV-1 infection compared to control cells. Human macrophages
      expressing TRIM5alpha(rh) were also found to be phenotypically and functionally
      normal, expressing the characteristic surface markers CD14, CD4, CCR5, CXCR4, MHC
      II, and B7.1. These results demonstrate that the species-specific restriction
      factor TRIM5alpha(rh) is effective in conferring HIV-1 resistance in a stem cell
      setting, thus paving the way for its application in AIDS gene therapy.

PMID- 16081322
TI  - Acute pain increases heart rate: differential mechanisms during rest and mental
      stress.
AB  - The main aim was to investigate if acutely stressed subjects have abnormal heart
      rate variability responses to acute pain. Efferent cardiac autonomic activity was
      assessed by analyzing RR interval variation in 26 male volunteers. Heart rate
      variability was measured as mean and standard deviation of normal RR intervals
      (mean RR, SDNN) and by power spectral analysis where high frequency (HF) and low
      frequency (LF) power were used as indexes of vagal function and of sympatho-vagal
      interaction, respectively. Coefficient of component variance in the LF and HF
      bands (CCV-LF, CCV-HF) was estimated to adjust for possible influences of
      different mean RR levels on power amplitude. Subjects received painful and non
      painful sural nerve stimulations during rest, during attention to pain, and
      during mental stress. Our results show that pain significantly decreased mean RR
      and increased LF power and CCV-LF during rest and during attention to pain. SDNN,
      HF power, and total power were not affected by pain. During mental stress, pain
      significantly decreased mean RR but failed to affect other heart rate variability
      parameters. We conclude that acute pain induced efferent cardiac sympathetic
      activation during rest and during attention to pain as LF power and CCV-LF
      increased without alterations of pure vagal heart rate variability measures.
      During mental stress, pain inhibited mean RR without changing heart rate
      variability measures suggesting that pain does not increase efferent cardiac
      sympathetic activity during mental stress. Pain induced decrease of mean RR
      during mental stress may be caused by the release of catecholamines into the
      systemic circulation.

PMID- 16081323
TI  - Association between antennal phenotype, wing polymorphism and sex in the genus
      Mepraia (Reduviidae: Triatominae).
AB  - Mepraia spinolai and Mepraia gajardoi (Hemiptera, Reduviidae) are only found in
      the arid regions of northern Chile. Mepraia is the only genus of Triatominae with
      marked wing polymorphism. Females of both species are micropterous, males of M.
      spinolai may be micropterous, brachypterous or macropterous, while males of M.
      gajardoi are always brachypterous. Because of this wing polymorphism, Mepraia can
      be used as a model to analyze morphological adaptations related to the flying
      activity and evolutionary relationships in the Triatominae. The study presented
      here analyses the antennal phenotype of the Mepraia species and carries out a
      comparison with the two species of Triatoma included in the spinolai complex
      (Triatoma eratyrusiformis and Triatoma breyeri). The analysis of the antennal
      phenotype of Mepraia showed a marked intraspecific phenotypic variability related
      with sex and wing condition. The number and length of multiporous trichoid
      sensilla (TH) on the pedicel are significantly higher and longer in winged males
      and are strongly reduced in females. The great length of the TH sensillum is an
      infrequent characteristic within Triatominae. The results show that phenetic
      distances between sexes are greater than between the two species. Similarity
      between the Mepraia species and T. eratyrusiformis was found as they all show
      long bristles (BR) and TH and two sized basiconic receptors (BA), a pattern that
      have not been observed in other species of Triatominae. These characters are not
      present in T. breyeri.

PMID- 16081324
TI  - Phylloplane yeasts from Portugal: seven novel anamorphic species in the
      Tremellales lineage of the Hymenomycetes (Basidiomycota) producing orange
      coloured colonies.
AB  - A survey of epiphytic yeasts on leaves of selected Mediterranean plant species
      collected at the 'Arrabida Natural Park' (Portugal) yielded about 850 isolates,
      mostly of basidiomycetous affinity. Amongst the basidiomycetes, 35 strains showed
      the following characteristics: production of orange-coloured colonies, ability to
      produce starch-like compounds, assimilation of D-glucuronic acid and/or inositol,
      inability to utilize nitrate, and formation of ballistoconidia by many of the
      isolates. This group of yeasts was assigned to the Tremellales lineage of the
      Hymenomycetes and was further characterised using a combination of conventional
      phenotypic identification tests with molecular methods, namely PCR fingerprinting
      and rDNA sequencing. Eight additional strains presumptively identified as Bullera
      armeniaca, B. crocea or Cryptococcus hungaricus were also studied. Twenty-eight
      strains could be assigned to or were phylogenetically related to recognised
      species of Dioszegia in the 'Luteolus clade', but the 15 remaining strains
      belonged to other clades within the Tremellales. Ten phylloplane isolates were
      identified as Dioszegia hungarica, one as D. aurantiaca, another as D. crocea and
      three others were ascribed to the recently described species D. zsoltii. Seven
      novel species, viz. Cryptococcus amylolyticus, C. armeniacus, C. cistialbidi,
      Dioszegia buhagiarii, D. catarinonii, D. fristingensis and D. takashimae, are
      proposed for the remaining strains that did not correspond to any of the hitherto
      recognised species.

PMID- 16081325
TI  - Enteral nutritional support in prevention and treatment of pressure ulcers: a
      systematic review and meta-analysis.
AB  - BACKGROUND: There have been few systematic reviews and no meta-analyses of the
      clinical benefits of nutritional support in patients with, or at risk of
      developing, pressure ulcers. Therefore, this systematic review and meta-analysis
      was undertaken to address the impact of enteral nutritional support on pressure
      ulcer incidence and healing and a range of other clinically relevant outcome
      measures in this group. METHODS: Fifteen studies (including eight randomised
      controlled trials (RCTs)) of oral nutritional supplements (ONS) or enteral tube
      feeding (ETF), identified using electronic databases (including Pub Med and
      Cochrane) and bibliography searches, were included in the systematic review.
      Outcomes including pressure ulcer incidence, pressure ulcer healing, quality of
      life, complications, mortality, anthropometry and dietary intake were recorded,
      with the aim of comparing nutritional support versus routine care (e.g. usual
      diet and pressure ulcer care) and nutritional formulas of different composition.
      Of these 15 studies, 5 RCTs comparing ONS (4 RCTs) and ETF (1 RCT) with routine
      care could be included in a meta-analysis of pressure ulcer incidence. RESULTS:
      Meta-analysis showed that ONS (250-500 kcal, 2-26 weeks) were associated with a
      significantly lower incidence of pressure ulcer development in at-risk patients
      compared to routine care (odds ratio 0.75, 95% CI 0.62-0.89, 4 RCTs, n=1224,
      elderly, post-surgical, chronically hospitalised patients). Similar results were
      obtained when a combined meta-analysis of ONS (4 RCT) and ETF (1 RCT) trials was
      performed (OR 0.74, 95% CI 0.62-0.88, 5 RCTs, n=1325). Individual studies showed
      a trend towards improved healing of existing pressure ulcers with disease
      specific (including high protein) versus standard formulas, although robust RCTs
      are required to confirm this. Although some studies indicate that total
      nutritional intake is improved, data on other outcome measures (quality of life)
      are lacking. CONCLUSIONS: This systematic review shows enteral nutritional
      support, particularly high protein ONS, can significantly reduce the risk of
      developing pressure ulcers (by 25%). Although studies suggest ONS and ETF may
      improve healing of PU, further research to confirm this trend is required.

PMID- 16081326
TI  - Pseudomonas aeruginosa in public swimming pools and bathroom water of patients
      with cystic fibrosis.
AB  - INTRODUCTION: Acquisition of Pseudomonas aeruginosa (PA) in the lungs of patients
      with cystic fibrosis (CF) is a marker of poor survival. PA is a ubiquitous
      pathogen prevalent in humid conditions. This study aimed to identify the
      prevalence of PA in public swimming pools, as well as from water taps. METHODS:
      Water was collected from public indoor and outdoor pools in the area of St.
      Gallen, Switzerland. In addition, standing and running water was sampled from
      bathroom water taps of 50 patients with CF. RESULTS: Outdoor pools: In 2002, none
      of the 72 specimens from 28 pools revealed PA. In 2003, three specimens from 46
      pools (7%) revealed PA, each were from a different paddling pool. Indoor pools:
      two of 128 specimens from 56 pools (4%) identified PA, both were from non-public
      hydrotherapy pools. Water taps: in winter, none of the 102 specimens was
      colonized with PA. in summer, only two out of 50 specimens of the standing water
      were positive for PA but none of the running water revealed PA. CONCLUSION: The
      prevalence of PA in public swimming pools and bathroom water taps in the eastern
      part of Switzerland is very low. On hot summer days, outdoor paddling pools and
      standing tap water can contain PA. This study does not support recommendations to
      avoid public swimming pools or running tap water if the water is maintained
      according to hygiene guidelines.

PMID- 16081327
TI  - Quantification of hydroxyproline in small amounts of skin tissue using isocratic
      high performance liquid chromatography with NBD-F as fluorogenic reagent.
AB  - In order to determine the collagen content of small amounts of skin tissue, we
      developed a new, simple and highly sensitive method of measuring the quantity of
      hydroxyproline (Hyp) using isocratic high performance liquid chromatography
      (HPLC) with a fluorogenic agent, 7-fluoro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-F).
      The recovery rate of Hyp and reproducibility of the assay were high, and the test
      was sensitive enough to detect Hyp in less than 1 mg of skin tissue. This method
      is clinically useful for ensuring accurate diagnosis and for monitoring specific
      skin conditions using small human skin samples collected in biopsies.

PMID- 16081328
TI  - Opposite roles of domains 2+3 of Escherichia coli EF-Tu and Bacillus
      stearothermophilus EF-Tu in the regulation of EF-Tu GTPase activity.
AB  - The effect of noncatalytic domains 2+3 on the intrinsic activity and
      thermostability of the EF-Tu GTPase center was evaluated in experiments with
      isolated domains 1 and six chimeric variants of mesophilic Escherichia coli (Ec)
      and thermophilic Bacillus stearothermophilus (Bst) EF-Tus. The isolated catalytic
      domains 1 of both EF-Tus displayed similar GTPase activities at their optimal
      temperatures. However, noncatalytic domains 2+3 of the EF-Tus influenced the
      GTPase activity of domains 1 differently, depending on the domain origin.
      Ecdomains 2+3 suppressed the GTPase activity of the Ecdomain 1, whereas those of
      BstEF-Tu stimulated the Bstdomain 1 GTPase. Domain 1 and domains 2+3 of both EF
      Tus positively cooperated to heat-stabilize their GTPase centers to attain
      optimal activity at a temperature close to the optimal growth temperature of
      either organism. This can be explained by a stabilization effect of domains 2+3
      on alpha-helical regions of the G-domain as revealed by CD spectroscopy.

PMID- 16081329
TI  - Solution structure of beta(2)-microglobulin and insights into fibrillogenesis.
AB  - The solution structure of human beta(2)-microglobulin (beta(2)-m) was determined
      by (1)H NMR spectroscopy and restrained modeling calculations. Compared to the
      crystal structure of type I major histocompatibility complex (MHC-I), where the
      protein is associated to the heavy-chain component, several differences are
      observed, i.e., increased separation between strands A and B, displacements of
      strand C' and loop DE, shortening of strands D and E. These modifications can be
      considered as the prodromes of the amyloid transition. Even minor charge changes
      in response to pH, as is the case with H31 imidazole protonation, trigger the
      transition that starts with unpairing of strand A. The same mechanism accounts
      for the partial unfolding and fiber formation subsequent to Cu(2+) binding which
      is shown to occur primarily at H31. Solvation of the protected regions in MHC-I
      decreases the tertiary packing by breaking the contiguity of the surface
      hydrophobic patches via surface charge cluster. Mutants or truncated forms of
      beta(2)-m can be designed to remove the instability from H31 titration or to
      enhance the instability through surface charge suppression. By monitoring the
      conformational evolution of wild-type protein and variants thereof, either in
      response or absence of external perturbation, valuable insights into intermediate
      structure and fibrillogenesis mechanisms are gained.

PMID- 16081330
TI  - Single mutation at P1 of a chymotrypsin inhibitor changes it to a trypsin
      inhibitor: X-ray structural (2.15 A) and biochemical basis.
AB  - Change in specificity, caused by the mutations at P1 site, of the serine protease
      inhibitors of different families is reported in the literature, but Kunitz (STI)
      family inhibitors are almost unexplored in this regard. In this paper, we present
      the crystal structure of a P1 variant of winged bean chymotrypsin inhibitor (WCI)
      belonging to Kunitz (STI) family, supplemented by biochemical, phylogenetic and
      docking studies on the mutant. A single mutation (Leu-->Arg) at P1 converted WCI
      to a strong inhibitor of trypsin with an association constant of 4.8x10(10) M(-1)
      which is comparable to other potent trypsin inhibitors of the family. The crystal
      structure (2.15 A) of this mutant (L65R) shows that its reactive site loop
      conformation deviates from that of WCI and adopts a structure similar to that of
      Erythrina caffra trypsin inhibitor (ETI) belonging to the same family. Mutation
      induced structural changes have also been propagated in a concerted manner to the
      neighboring conserved scaffolding residue Asn14, such that the side chain of this
      residue took an orientation similar to that of ETI and optimized the hydrogen
      bonds with the loop residues. While docking studies provide information about the
      accommodation of non-specific residues in the active site groove of trypsin, the
      basis of the directional alteration of the reactive site loop conformation has
      been understood through sequence analysis and related phylogenetic studies.

PMID- 16081334
TI  - Finding a path through the health unit: practical experience of Ugandan patients.
AB  - Finding one's way through a health facility is not necessarily an easy task for
      Ugandan patients. Our understanding of how people succeed in doing so, and of the
      obstacles they encounter on their way, is incomplete if we focus only on the
      cognitive level of the clinical encounter. Much research in public health and
      medical anthropology implicitly works with the notion that agency is located in
      the mind and that cognitive understanding is a precondition for practice. Based
      on material from eastern Uganda, this article explores the practical experience
      of Ugandan patients and their relatives and reflects upon the ways in which this
      notion of agency has often caused us to confuse the spectator's point of view
      with the actor's point of view. Thus, as Pierre Bourdieu has argued, we are made
      to look for answers to "questions that practice never asks because it has no need
      to ask them."

PMID- 16081335
TI  - Facing HIV: body shape change and the (in)visibility of illness.
AB  - Illness is commonly invested with considerable stigma because of its tendency to
      evoke charged meanings around corporeality, selfhood, suffering, and mortality.
      Perhaps more than any contemporary disease HIV/AIDS has served as a powerful
      signifier for a range of cultural anxieties. Given the resultant stigma, HIV
      becomes very much a question of visibility. This article explores the visibility
      of HIV within the Sydney gay community with reference to lipodystrophy, an
      unusual process of fat redistribution caused by HIV therapy that manifests in a
      series of distinctive body shape changes that have come to signify HIV socially.
      Conceived through the cultural lenses of AIDS, medicine, illness, and body image,
      lipodystrophy is largely constituted as negative and shameful, as Other in the
      ethnographic domain. I examine how this conception is reproduced and contested in
      narratives and experiences among HIV-positive gay men who have lipodystrophy.
      Their stories suggest diverse "ways of seeing" lipodystrophy that reveal an
      ambivalent potential of visibility not only as a medium of stigma,
      differentiation, and discrimination but also as a medium of affinity, empathy,
      and desire. These localized patterns of illness visibility are explored in
      relation to the circulation of meanings within a broader social sense and their
      significance in terms of a more general consideration of representational
      practices and their social and ethical implications, with specific attention
      given to educational and media representations of HIV/AIDS in Australia and also
      in the United States.

PMID- 16081336
TI  - When "the program is good, but the disease is better": lessons from Peru on drug
      resistant tuberculosis.
AB  - This is a qualitative study of the politics of public health surrounding a
      resurgent tuberculosis epidemic in Lima, Peru during the 1990s. The paper traces
      the role of debt and neoliberal economics in creating conditions for the
      epidemic, and the reforms that turned Peru's TB program into a model for treating
      drug-susceptible disease by 1996. Despite this success, public health officials
      were blind-sided by the appearance of drug-resistant TB in the late 1990s when
      their "good" program turned out to be not good enough. The study follows the
      conflict, and eventual collaboration, that ensued between the Ministry of Health
      and a local NGO affiliated with Boston-based Partners in Health, which undertook
      a radical program of community-based directly-observed therapy (DOTS-Plus) to
      treat drug-resistant patients who otherwise would have died. Lessons from this
      case are relevant to many international settings where "hot-spots" of drug
      resistant TB currently exist and go untreated, posing a threat to the success of
      national TB control programs.

PMID- 16081338
TI  - Dilation and reduced distensibility of rat carotid artery with aging.
AB  - To better understand the pathogenesis of increased arterial stiffening with
      aging, the relative contribution of geometry (lumen diameter) and stiffening of
      wall components (elastic modulus) to reduced distensibility of rat carotid artery
      in the early stages of aging was investigated. Pressure-volume (distensibility)
      relationships were measured in excised, in vitro perfused right carotid artery of
      7-. 10- and 20-month old, male Sprague-Dawley rats. The left carotid artery of
      rats was perfusion-fixed in situ at 100 mm Hg and then embedded in epoxy for
      morphometric measurements. Compared to 7- and 10-month old rats, there was
      dilation (increased lumen diameter), increased wall thickness, and reduced
      distensibility and unchanged elastic moduli of carotid artery in 20-month old
      rats. Dilation (with early recruitment of collagen fibrils during pressure rise)
      rather than increased stiffness of wall components appears to be the cause of
      reduced distensibility of rat carotid artery in the early stages of aging.

PMID- 16081339
TI  - Distribution of blood pressure and heart rate among adults in Jordan: a national
      survey.
AB  - Knowledge of population distribution of blood pressure is useful for predicting
      blood pressure related health burden as well as for planning prevention strategy.
      The aim of this investigation is to determine the distribution of systolic blood
      pressure (SBP), diastolic blood pressure (DBP), arterial blood pressure (ABP),
      and heart rate among normotensive adults resident from all regions of Jordan.
      This study is the first detailed description of these parameters in Jordan at a
      national level. A total of 14,310 adult males (7,400) and females (6,910) were
      selected randomly in various regions of Jordan. For each individual, the SBP,
      DBP, and heart rate were measured three times with 10-15-minute intervals in the
      sitting position and at the resting state. The ABP was calculated from the
      measured SBP and DBP. The mean values were distributed according to age and sex.
      Student's t-test was used for statistical analysis. Males had significantly
      higher SBP, DBP, ABP, and heart rate values than females. There also was an
      increase of these values with advancing age. Moreover, cases of hypotension and
      bradycardia were higher in the female population than in males, whereas cases of
      hypertension and tachycardia were higher in males. Distribution of blood pressure
      and heart rate among adults in Jordan was determined. Cases of undiagnosed
      hypertension, hypotension, and an increase or a decrease in heart rate were
      detected through our random screening in the target population. Individuals with
      these abnormalities require further clinical investigations to confirm or exclude
      these findings.

PMID- 16081340
TI  - Efficacy and duration of action of the four selective angiotensin II subtype 1
      receptor blockers, losartan, candesartan, valsartan and telmisartan, in patients
      with essential hypertension determined by home blood pressure measurements.
AB  - Our objective was to compare the efficacy and duration of action of 4 angiotensin
      II receptor blockers (ARBs)--losartan (25-100 mg), candesartan (2-12 mg),
      valsartan (40-80 mg), and telmisartan (10-40 mg)-in patients with essential
      hypertension using self-measurement of blood pressure at home (home BP) and to
      examine the differential effect of the four ARBs on home pulse pressure (home
      PP). After a 2-week run-in period, each of the 4 ARBs was assigned to subjects
      who were diagnosed as having hypertension on the basis of home BP and who were
      over 30 years old. The subjects were asked to take the ARB once daily in the
      morning and to measure home BP once in the evening and in the morning. We
      compared the efficacy of each ARB on home BP and home PP and assessed the
      duration of the BP-lowering effect using the morning effect versus evening effect
      ratio (M/E ratio). The antihypertensive effects of telmisartan on home systolic
      BP (SBP) both in the evening and in the morning and on home diastolic BP (DBP) in
      the morning were significantly greater than those of losartan. The effect of each
      ARB on home BP in the morning and in the evening was expressed as a ratio (M/E
      ratio). The M/E ratios of SBP/DBP in patients treated with losartan, candesartan,
      valsartan, and telmisartan were 0.49/0.16, 0.69/1.01, 0.82/0.88, and 0.88/0.88,
      respectively. The home PP-lowering effect was greater for valsartan and
      telmisartan than for losartan and candesartan in the morning. Among the 4 ARBs,
      the duration of the BP-lowering effect of losartan did not persist throughout 24
      hr. The effects of the other 3 ARBs, in particular telmisartan, persisted over 24
      hr when they were administered once daily in the morning. In addition, the
      duration of the PP-lowering effect was similar to that of the BP-lowering effect.
      Such long-acting property of several ARBs is essential for the modern
      antihypertensive treatment, and home BP measurements are useful for determining
      the duration of action of antihypertensive drugs. Losartan, 25 mg a day, which is
      usually used as an initial dose in Japan, is apparently insufficient to obtain
      adequate antihypertensive effect and sufficient duration of action.

PMID- 16081341
TI  - Congenital episodic hypertension.
AB  - We report two patients who have congenital episodic severe hypertension and
      dysautonomic symptoms. Their hypertensive episodes were successfully treated with
      antiadrenergic and antihypertensive agents. Their clinical course improved with
      intermittent treatment of their episodes of severe hypertension. These patients
      do not fit previously described disorders.

PMID- 16081342
TI  - Modulation of nitric oxide synthase activity in brain, liver, and blood vessels
      of spontaneously hypertensive rats by ascorbic acid: protection from free radical
      injury.
AB  - End organ damage in essential hypertension has been linked to increased oxygen
      free radical generation, reduced antioxidant defense, and/or attenuation of
      nitric oxide synthase (NOS) activity. Ascorbic acid (AA), a water-soluble
      antioxidant, has been reported as a strong defense against free radicals in both
      aqueous and nonaqueous environment. In this study we examined the hypothesis that
      antioxidant ascorbic acid may confer protection from increased free radical
      activity in brain, liver, and blood vessels of spontaneously hypertensive rats
      (SHR). Male SHRs were divided into groups: SHR + AA (treated with AA, 1
      mg/rat/day; for 12 weeks) or SHR (untreated). Wister-Kyoto rats (WKY) served as
      the control. Mean systolic blood pressure (SBP) in treated and untreated SHR was
      145 +/- 7 mmHg and 142 +/- 8 mmHg, respectively. AA treatment prevented the
      increase in systolic blood pressure in SHR by 37 +/- 1% (p < 0.05). NOS activity
      in the brain, liver, and blood vessels of WKY rat was 1.82 +/- 0.02, 0.14 +/-
      0.003, and 1.54 +/- 0.06 pmol citruline/mg protein, respectively. In SHR, total
      NOS activity was significantly reduced by 52 +/- 1%, 21 +/- 3%, and 44 +/- 4%,
      respectively. AA increased NOS activity in brain, liver, and blood vessels of SHR
      from 0.87 +/-.03, 0.11 +/-.01, and 0.87 +/-.08 pmol citruline/mg protein to 0.93
      +/- 0.01, 0.13 +/- 0.001, and 1.11 +/- 0.03 pmol citruline/mg protein (p < 0.05),
      respectively. Lipid peroxides in the brain, liver, and blood vessels from WKY
      rats were 0.87 +/- 0.06, 0.11 +/- 0.005, and 0.47 +/- 0.04 nmol MDA equiv/mg
      protein, respectively. In SHR, lipid peroxides in brain, liver, and blood vessels
      were significantly increased by 40 +/- 3%, 64 +/- 3%, and 104 +/- 13%,
      respectively. AA reduced lipid peroxidation in liver and blood vessels by 17 +/-
      1% and 34 +/- 3% but not in brain. Plasma lipid peroxides were almost doubled in
      SHR (p < 0.01) together with a reduction in total antioxidant status (6 +/- 0.1%;
      p < 0.05), nitrite (53 +/- 2%; p < 0.05) and superoxide dismutase (SOD) activity
      (36 +/- 2%; p < 0.05). AA treatment reduced plasma lipid peroxide (p < 0.001),
      and increased TAS (p < 0.001), nitrite (p < 0.001), and SOD activity (p < 0.001).
      From this study, we conclude that brain, liver, and blood vessels in SHR are
      susceptible to free radical injury, which reduces the availability of NO either
      by scavenging it or by reducing its production via inhibiting NOS. In addition,
      brain, liver, and blood vessels in SHR; may be protected by antioxidant, which
      improves total antioxidant status, and SOD thus may prevent high blood pressure
      and its complications.

PMID- 16081343
TI  - A common haplotype on methylenetetrahydrofolate reductase gene modifies the
      effect of angiotensin-converting enzyme inhibitor on blood pressure in essential
      hypertension patients--a family-based association study.
AB  - Our recent study indicated that MTHFR C677T polymorphism may involve in genetic
      control of blood pressure response to treatment by benazepril, an ACE inhibitor.
      Currently, we proposed to further investigate whether short-term blood pressure
      response to benazepril, was modulated by haplotypes re-constructed from both
      C677T and A1298C polymorphisms in MTHFR gene. A total of 410 hypertensive
      patients recruited from 344 nuclear families were treated orally with benazepril
      at a daily dosage of 10 mg for 15 consecutive days. Blood pressures were measured
      at baseline and on the 16th day of treatment. In addition, 689 family members of
      these patients were also genotyped. Among these patients, the frequency of MTHFR
      A1298C AA, AC and CC genotypes was 74.4%, 23.9%, and 1.7%, respectively. The
      frequency of MTHFR C677T CC, CT and TT genotypes was 23.7%, 51.2%, and 25.1%,
      respectively. Only three haplotypes, 677T-1298A (50.8%), 677C-1298A (35.7%), and
      677C-1298C (13.5%) were re-constructed. Multivariate regression models with
      generalized estimating equation (GEE) correction detected that the individuals
      carrying one copy of haplotype 677C-1298C had significantly lower diastolic and
      systolic blood pressure response (DeltaDBP and DeltaSBP) to benazepril treatment
      (p= 0.003 and p =0.043, respectively), in comparison to those without haplotype
      677C-1298C. The results of family-based association test further confirmed that
      haplotype 677C-1298C was more frequently transmitted in subjects with either
      lower residual of DeltaDBP or DeltaSBP. For residual of DeltaDBP, the p-values
      are 0.007 in an additive model and 0.005 in a dominant model. For residual of
      DeltaSBP, the p-values are 0.009 in an additive model and 0.006 in a dominant
      model. Our findings suggest that MTHFR 677C-1298C haplotype modulate blood
      pressure responsiveness to shortterm treatment of ACE inhibitor in Chinese
      essential hypertensive patients.

PMID- 16081344
TI  - Experimental-induced periodontitis is exacerbated in spontaneously hypertensive
      rats.
AB  - Studies show that systemic diseases such as diabetes, hyperthyroidism,
      osteoporosis, and dyslipidemia may influence periodontal inflammation. However,
      few studies relate the influence of arterial hypertension on periodontitis. The
      present study was undertaken to assess the severity of the experimental ligature
      induced periodontitis in an experimental model of genetic arterial hypertension.
      The experimental periodontitis model was induced in 6 spontaneously hypertensive
      rats (SHR) and 6 Wistar normotensive rats (NT) by cotton ligature, which was
      placed subgingivaly around the neck of the first left inferior molar tooth. In
      the same animal, the first right molar tooth was sham-ligated and used as a
      control. After 7 days, the mean arterial pressure (MAP) and heart rate (HR) were
      recorded in conscious animals. As expected, MAP was significantly higher in SHR
      (151 +/- 6 mmHg) than in NT (105 +/- 3 mmHg), without significant differences in
      HR. The histopathologic examination of the periodontal structure showed alveolar
      integrity and lack of neutrophils and osteoclasts in the control side of both SHR
      and NT. In contrast, examination of the ligated side in all animals showed
      collagen degradation in the alveolar process from a moderate (50%) to severe
      (50%) level in SHR and mild in NT (100%). These data show that experimental
      periodontitis, characterized by the spreading of the inflammatory process from
      the gingiva deep into periodontium tissues, is greatly exacerbated in SHR.

PMID- 16081345
TI  - Relation between QRS amplitude and left ventricular mass in the initial stage of
      exercise-induced left ventricular hypertrophy in rats.
AB  - The aim of the study was to analyze the relationship between QRS amplitude and
      left ventricular mass (LVM) in early stages of two different experimental models
      of left ventricular hypertrophy (LVH) in rats: in exercise-induced hypertrophy
      and pathological hypertrophy due to genetically conditioned pressure overload.
      Three groups of experimental animals were studied: healthy control Wistar-Kyoto
      rats (WKYs), spontaneously hypertensive rats (SHRs), and WKY rats exposed to
      training by intermittent swimming (SWIM). Orthogonal electrocardiograms were
      recorded in each group at the age of 12 and 20 weeks, and the maximum spatial QRS
      vector (QRSmax) was calculated. Then the animals were sacrificed and LVM was
      measured. The specific potential of myocardium (SP) was calculated as a ratio of
      QRSmax to LVM. The QRSmax values did not follow the changes in LVM. At the end of
      the follow-up period, the highest values of QRSmax were recorded in the control
      WKY rats (0.80 +/- 0.05 mV). The QRSmax values in both groups with experimental
      LVH were significantly lower as compared with control animals (SHR 0.44 +/- 0.02
      mV, p < 0.001; SWIM 0.53 +/- 0.04 mV, p < 0.001). Similarly, the SP values were
      significantly lower in both groups with experimental LVH as compared with control
      animals (SHR 0.42 +/- 0.02 mV/g, p < 0.001; SWIM 0.55 +/- 0.05 mV/g, p < 0.001).
      A decrease in QRSmax and SP was observed in both models of experimental LVH. We
      attributed these findings to the changes in electrogenetic properties of
      myocardium in the early stage of developing LVH. In other words, it is changes of
      nonspatial determinants that influence the resultant QRS voltage in terms of the
      solid angle theory.

PMID- 16081347
TI  - Biology of cord blood cells and future prospects for enhanced clinical benefit.
AB  - Cord blood (CB) has served as a clinically beneficial source of hematopoietic
      stem (HSC) and progenitor (HPC) cells for transplantation and correction of a
      large number of malignant and non-malignant disorders. The capacity of CB to
      perform these functions is intimately related to the quality and quantity of HSC
      and HPC present in CB. This review covers the biology of HSC and HPC, efforts to
      expand these cells ex vivo for enhanced clinical utility that has thus far not
      been very successful, and recent studies on attempts to enhance the homing and
      engrafting capability of HSC as an alternative means for more effective use of
      the limited numbers of CB cells collected. This review also highlights the
      presence in CB of mesenchymal stem cells, unrestricted somatic stem cells,
      endothelial progenitor cells and immune cells. The presence and biology of these
      non-HSC/HPC may open up future possibilities for additional clinical benefit of
      CB, a product considered mainly for discard before its clinical transplantation
      potential was realized in the late 1980s.

PMID- 16081348
TI  - History of the clinical use of umbilical cord blood hematopoietic cells.
AB  - The first cord blood (CB) transplant was performed in 1988 in a patient with
      Fanconi anemia. The donor was his HLA-identical sister who was known by pre-natal
      diagnosis to be HLA identical and not affected by the Fanconi mutation. The CB
      was collected and cryopreserved at birth. The transplant was successful without
      GvHD and the patient is currently alive and free of disease more than 15 years
      after transplant, with full hematologic and immunologic donor reconstitution. At
      the time of the first transplant, little was known about the biologic properties
      of CB cells and it was thanks to the pioneering work of H. E. Broxmeyer and E. A.
      Boyse, who studied the progenitor cell content of CB, and of A. D. Auerbach, who
      realized the pre-natal diagnosis of Fanconi anemia, that this transplant was
      possible. Since this first transplant, many questions have been answered but
      others are still open for further research. For example: would a single CB unit
      contain enough stem cells to permanently engraft children and adults? Would
      maternal cell contamination in fetal blood engraft and give severe GvHD? What are
      the immunologic properties of CB cells? How does it interfere with GvHD, GvL and
      immune reconstitution? Is the immune immaturity of CB lymphocytes able to
      overcome the HLA barrier and authorize HLA-mismatched transplants? Is it possible
      to establish CB banks for unrelated and related transplants? What would be the
      criteria for collection, quality control and cryopreservation?

PMID- 16081349
TI  - Cord blood transplantation in adult patients.
AB  - Early clinical reports outlining outcomes for primarily pediatric patients
      undergoing UCB transplantation point to delayed time to hematopoietic recovery
      and favorable incidence and severity of GvHD. Recently, clinical reports in adult
      patients identified the feasibility of UCB transplantation for those patients
      lacking an available histocompatible-related or unrelated adult donor Intensive
      clinical and laboratory research is ongoing focused on strategies to foster UCB
      allogeneic donor engraftment thereby allowing wider application of this stem cell
      source for patients requiring allogeneic transplantation.

PMID- 16081350
TI  - Ex vivo expansion of umbilical cord blood.
AB  - The efficacy of cord blood (CB) transplantation is limited by the low cell dose
      available. Low cell doses at transplant are correlated with delayed engraftment,
      prolonged neutropenia and thrombocytopenia and elevated risk of graft failure. To
      potentially improve the efficacy of CB transplantation, approaches have been
      taken to increase the cell dose available. One approach is the transplantation of
      multiple cord units, another the use of ex vivo expansion. Evidence for a
      functional and phenotypic heterogeneity exists within the HSC population and one
      concern associated with ex vivo expansion is that the expansion of lower
      'quality' hematopoietic progenitor cells (HPC) occurs at the expense of higher
      'quality' HPC, thereby impacting the reserve of the graft. There is evidence that
      this is a valid concern while other evidence suggests that higher quality HPC are
      preserved and not exhausted. Currently, ex vivo expansion processes include: (1)
      liquid expansion: CD34+ or CD133+ cells are selected and cultured in medium
      containing factors targeting the proliferation and self-renewal of primitive
      hematopoietic progenitors; (2) co-culture expansion: unmanipulated CB cells are
      cultured with stromal components of the hematopoietic microenvironment,
      specifically mesenchymal stem cells (MSC), in medium containing growth factors;
      and (3) continuous perfusion: CB HPC are cultured with growth factors in
      'bioreactors' rather than in static cultures. These approaches are discussed.
      Ultimately, the goal of ex vivo expansion is to increase the available dose of
      the CB cells responsible for successful engraftment, thereby reducing the time to
      engraftment and reducing the risk of graft failure.

PMID- 16081351
TI  - Human umbilical cord blood cells: a new alternative for myocardial repair?
AB  - Cell therapy for myocardial disease is a rapidly progressive field. However,
      present strategies of cell transplantation into the infarcted myocardium have
      limitations from practical points of view. One of the biggest challenges is to
      achieve a sufficient number of suitable cells. Umbilical cord blood (UCB), an
      unlimited source of stem/progenitor cells that could be used for transplantation
      into the injured heart, is readily available. The aim of our review is to
      describe the potential and prospect of UCB as a new supplier of cells for
      myocardial repair. The use of UCB stem cells might be of importance to elderly
      and sick people in whom the availability of autologous stem cells is limited.

PMID- 16081352
TI  - Umbilical cord blood-derived cells for tissue repair.
AB  - Hematopoietic tissue-derived cells, including stem cells, have been shown to
      generate solid organ tissue-specific cells. Besides bone marrow and peripheral
      blood, umbilical cord blood (UCB) has the advantage of being an easily accessible
      stem cell source provided as a banked cell product. Using the xenogeneic human
      into NOD/SCID mouse stem cell transplant model preliminary data suggest UCB
      derived tissue-specific cells generated in liver, pancreas, CNS and endothelium.
      In a clinical sex-mismatched UCB transplant setting Y-positive, UCB-derived
      gastrointestinal epithelial cells and CNS-specific cells have been identified in
      female patients. The potential therapeutic use of UCB cells for tissue repair is,
      however, limited by a low total stem cell number available and by HLA-disparity.

PMID- 16081353
TI  - Current status of genetic modification of T cells for cancer treatment.
AB  - Clinical studies of adoptive immunotherapy with T cells have shown activity
      directed at hematologic and solid malignancies and viral infections. Genetic
      modification of infused T cells offers the prospect of improving such therapies
      and has already been used to track infused T cells, insert suicide genes and
      redirect the immune response towards specific Ag. Pre-clinical studies are
      evaluating novel approaches to genetically modify T cells to confer resistance to
      tumor evasion mechanisms. There is also increasing interest in developing suicide
      gene strategies as a failsafe mechanism to eradicate genetically modified cells
      should adverse effects occur.

PMID- 16081354
TI  - In vitro and in vivo induction of bone formation based on ex vivo gene therapy
      using rat adipose-derived adult stem cells expressing BMP-7.
AB  - BACKGROUND: Adipose-derived adult stem (ADAS) cells are multipotent cells capable
      of differentiating into osteoblasts, adipocytes and chondrocytes. The aim of this
      study was to determine whether BMP-7-expressing ADAS cells would elicit bone
      formation invitro and in vivo. METHODS: ADAS cells were harvested from Lewis rats
      and transduced with adenovirus carrying the recombinant human bone morphogenetic
      protein-7 (Ad-BMP-7) gene. Untransduced cells and cells transduced with
      adenovirus carrying the enhanced green fluorescence protein (Ad-EGFP) gene served
      as controls. BMP-7 expression was assessed by RT-PCR, immunofluorescence on day
      1, and Western blot on days 4, 8 and 12. Alkaline phosphatase (ALP) activity was
      assayed on days 2, 4, 6, 8, 10 and 12. Osteocalcin production and bone nodule
      formation were detected by immunohistochemistry and von Kossa stain on day 12. A
      total of 1 x 10(6) cells mixed with type I collagen were implanted into the
      subcutaneous pocket in Lewis rat and subjected to histologic analysis 1, 2 and 4
      weeks post-implantation. RESULTS: The Ad-BMP-7-transduced ADAS cells expressed
      BMP-7 at both mRNA and protein levels. ALP activity was detected in Ad-BMP-7
      transduced cells from day 2 to day 12, peaking on day 8. Osteocalcin production
      and matrix mineralization further confirmed that these cells differentiated into
      osteoblasts and induced bone formation in vitro. Histologic examination revealed
      that implantation of BMP-7-expressing ADAS cells could induce new bone formation
      in vivo. DISCUSSION: ADAS cells would be a promising source of adult autologous
      stem cells for BMP gene therapy and tissue engineering.

PMID- 16081355
TI  - Expression of cardiomyocytic markers on adipose tissue-derived cells in a murine
      model of acute myocardial injury.
AB  - Animal and early clinical studies have provided evidence suggesting that
      intracoronary administration of autologous bone marrow-derived cells results in
      improved outcome following myocardial infarction. Animal studies with cultured
      marrow stromal cells (MSC) have provided similar data. Cells with properties that
      are similar to MSC have been identified in adipose tissue. Other groups have
      demonstrated in vivo differentiation of adipose tissue-derived cells (ADC) into
      cells exhibiting biochemical and functional markers of cardiac myocytes,
      including spontaneous beating. Based on these observations, the objective of the
      present study was to determine whether ADC might undergo similar differentiation
      in vivo in the context of myocardial injury.ADC were isolated from subcutaneous
      adipose tissue of Rosa26 mice (which express the beta-galactosidase transgene in
      almost every tissue) and injected into the intraventricular chamber of B6129S
      recipient mice immediately following induction of myocardial cryoinjury. Groups
      of recipients were euthanized at 24 hours, 7 and 14 days post surgery and
      examined for the presence of donor-derived cells within the heart.Beta-gal
      positive cells were identified in the infarcts of ADC-treated animals. No
      staining was observed in uninjured myocardium or in infarcts of control animals.
      Immunohistochemical analysis revealed co-expression of beta-gal with Myosin Heavy
      Chain, Nkx2.5 and with Troponin I. Co-expression of beta-galactosidase with
      Connexin 43, CD31, von Willebrand factor, MyoD or CD45 was not detected.Thus,
      these data indicate that adipose tissue contains a population of cells that has
      the ability to engraft injured myocardium and that this engraftment is associated
      with expression of cardiomyocytic markers by donor-derived cells.

PMID- 16081356
TI  - Stimulation of chondrocytes in vitro by gene transfer with plasmids coding for
      epidermal growth factor (hEGF) and basic fibroblast growth factor (bFGF).
AB  - Human epidermal growth factor (hEGF) and basic fibroblast growth factor (bFGF)
      influence critical characteristics of chondrocytes. The effects on metabolism and
      differentiation were evaluated following transfection using specific plasmids
      coding for both cytokines. Chondrocytes were isolated from femoral head cartilage
      of patients undergoing a hip arthroplasty for femoral neck fracture. Following
      collagenase-digestion, cells were cultured in monolayers, and cell proliferation,
      glucosaminoglycan-production and collagen type II expression were monitored 10
      days after isolation. Addition of recombinant hEGF and bFGF resulted in a
      significant increase in cell proliferation and glucosaminoglycan production.
      Chondrocytes were transfected with vectors coding for either hEGF or bFGF and the
      production of these proteins was measured in supernatants by ELISA. Expression
      kinetics showed different patterns: hEGF was detectable 2.5 days following
      transfection and peaked at day 5.5, whereas bFGF-production reached its maximum
      1.5 days after transfection, declining thereafter. Chondrocytes endogenously
      produced significant amounts of bFGF within 5 days following isolation.
      Proliferation of hEGF-transfected cells increased up to 81%; bFGF-transfection
      caused an increase up to 76%. Similarly, glucosaminoglycan-production was
      enhanced up to 120% by hEGF-transfection and 37% by bFGF transfection,
      respectively. Collagen type II production decreased following transfection with
      both plasmids. Temporary in vitro gene transfer of the growth factors hEGF and
      bFGF provides a method to stimulate chondrocyte proliferation and induces signs
      of dedifferentiation, which would limit a reasonable clinical application.

PMID- 16081357
TI  - New developments in stem cell biology and therapy. First meeting report from the
      working group of the German Society for Hematology and Oncology.
AB  - The call for the meeting which took place in Heidelberg 13 January 2005, resulted
      in a high number of contributions covering a diversity of topics: embryonal stem
      cell research; molecular signaling pathways; assay systems for primitive,
      mesenchymal and epithelial stem cells; markers for transdifferentiation; and
      theoretical considerations including biomathematical modeling of stem cell
      development. The program was rounded off by pre-clinical and clinical
      applications of stem cell therapies, including new mobilization agents, treatment
      of myocardial infarction and chemoprotective gene transfer to stem cells.

PMID- 16081358
TI  - Human anti-immunoglobulin antibodies interfering in immunometric assays.

PMID- 16081359
TI  - Patients with atherosclerosis may have increased circulating levels of 27
      hydroxycholesterol and cholestenoic acid.
AB  - Extrahepatic sterol 27-hydroxylase (CYP27) appears to have a role in the
      elimination of excess cholesterol from various cells, particularly macrophages,
      and there is a net flux of 27-hydroxyycholesterol and its metabolites from
      different extrahepatic sources to the liver. In this study we tested the
      hypothesis that patients with advanced atherosclerosis may have higher levels of
      27-oxygenated products in the circulation than control subjects. Concordant with
      previous studies, a strong correlation was observed between circulating levels of
      27-hydroxycholesterol and cholesterol, in both healthy subjects and subjects with
      hypercholesterolemia and documented atherosclerosis. A group of male subjects
      with normal or only slightly elevated serum cholesterol and rapidly progressing
      carotid atherosclerosis (n = 20) had serum levels of 27-oxygenated cholesterol
      not statistically different from those of a matched group of subjects with little
      or no development of atherosclerosis (n = 20). The situation was similar in a
      group of patients (n = 20) with advanced general atherosclerosis associated with
      severe clinical symptoms. Among the two groups of patients with atherosclerosis,
      a few patients had relatively high levels of 27-oxygenated products. Among the
      healthy controls, two healthy volunteers (brother and sister) were found to have
      high levels of 27-hydroxycholesterol, most probably due to genetic reasons. The
      possibility is discussed that the high levels of 27-oxygenated products in the
      circulation of a few patients with atherosclerosis may be related to high amounts
      of active macrophages present in atherosclerotic lesions. In view of the number
      of factors that could affect the levels in the circulation, other explanations
      cannot be ruled out. At the present state of knowledge, measurements of
      circulating levels of 27-oxygenated metabolites do not seem to add useful
      information about the atherosclerotic process.

PMID- 16081360
TI  - Problematic determination of serum growth hormone: experience from external
      quality assurance surveys 1998-2003.
AB  - The objective of the present study was to start a new external quality assurance
      survey (EQAS) for the determination of serum growth hormone (GH) using pooled
      serum specimens as quality-assurance samples. To give good coverage of multiple
      forms of GH, the specimens included sera from GH-deficient and acromegalic
      patients as well as from persons showing a normal response in GH provocation
      tests. In one survey the quality-control specimens were spiked with exogenous 22
      kD GH to obtain some idea of the specificity and GH recovery of the assays. The
      EQA surveys of 1998-2003 were organized by Labquality of Helsinki in cooperation
      with three university hospital laboratories in Finland. The number of
      participating laboratories ranged from 8 to 14. During 1998-2003, gratifying
      methodological harmonization occurred in the participating group, as the
      participants switched to the immunometric detection principle, the number of
      method applications decreasing from 7 to 3. In 1998 the 14 participating
      laboratories reported five different conversion factors (from microg/l to mU/l),
      whereas in 2003 7 of the 8 participants reported the same factor. Despite the
      harmonization trend among participating laboratories, further efforts are needed,
      because marked method-based differences still exist. This dialogue should include
      kit manufacturers, laboratory experts, EQA organizations and clinicians using the
      test results.

PMID- 16081361
TI  - Procalcitonin as a marker of postoperative complications.
AB  - OBJECTIVE: Procalcitonin (PCT) is a 116 amino acid peptide that functions as a
      pro-hormone for calcitonin in the C cells of the thyroid gland. Large quantities
      of intact PCT are present in the blood of patients with sepsis, particularly when
      organ dysfunction occurs. PCT has been proposed as an early marker of
      postoperative complications. The aim of this study was to examine the diagnostic
      accuracy of PCT as a marker of postoperative complications by systematically
      reviewing the existing literature. MATERIAL AND METHODS: The databases PubMed,
      Embase and the Cochrane Library were searched to find studies on the diagnostic
      accuracy of PCT in the postoperative phase. Primary studies were retrieved using
      specific inclusion and exclusion criteria. RESULTS: A total of nine studies were
      included. These studies were heterogeneous regarding the spectrum of patients,
      complications, design and methodological quality according to QUADAS (quality
      assessment of studies of diagnostic accuracy). This could explain the marked
      variation in diagnostic accuracy. Considering all types of complications the
      sensitivity ranged from 37% to 100% and the specificity from 70% to 100%. On
      examining the infectious complications separately, it was found that the
      sensitivity ranged from 70% to 86% and the specificity from 45% to 98%.
      CONCLUSIONS: Owing to a pronounced heterogeneity among the existing studies, the
      diagnostic accuracy of PCT as a marker for postoperative complications is not yet
      sufficiently clarified.

PMID- 16081362
TI  - Acute and long-term effects of winter swimming and whole-body cryotherapy on
      plasma antioxidative capacity in healthy women.
AB  - The effects of severe cold stress on total peroxyl radical trapping antioxidant
      capacity of plasma (TRAP) were studied in two groups of healthy women: a whole
      body cryotherapy group (WBC, n = 10) and a winter swimming group (WS, n = 10).
      The biovariability of TRAP values was also analysed. The WBC group was exposed to
      -110 degrees C for 2 min, whereas the exposure for the WS group lasted 20 s in
      ice-cold water. Sessions were organized three times per week for 12 weeks. Blood
      specimens were collected at 2, 4, 8 and 12 weeks at rest, 2 and 35 min after the
      cold exposures and at the corresponding times without cold exposure on a separate
      day. Conventional methods were used to determine TRAP values. The between-subject
      variation was 13.6% and the within-subject variation 6.4%. The index of
      individuality was 0.46, and the index of heterogeneity was 0.079. These results
      indicate a marked heterogeneity among subjects. During the first 4 weeks, the
      mean TRAP value significantly increased at 2 min after cold exposure in the WBC
      group, returning to baseline 35 min after the exposure. Similar changes were
      observed in the WS group. However, all changes due to cold were relatively mild
      (<5%). After 4 weeks no changes in TRAP values after the cold exposures were
      noticed and no long-term changes in basal TRAP values were observed. In the main,
      regular WBC and WS do not seem to be harmful as far as plasma antioxidative
      capacity is concerned.

PMID- 16081363
TI  - Absence of high-affinity calreticulin autoantibodies in patients with systemic
      rheumatic diseases and coeliac disease.
AB  - Calreticulin has been reported to be an autoantigen in various autoimmune
      connective tissue diseases and in coeliac disease. Previous studies have used
      incubation buffers with low salt and low detergent concentrations (low stringency
      conditions) with serum albumin or other proteins as a blocking agent. Using these
      conditions we found a relatively high level of non-specific binding in many sera.
      Antibodies to proteins that are used as blocking reagents in ELISA (bovine serum
      albumin (BSA), ovalbumin, skimmed milk powder) are frequently present in sera,
      and these may cause false-positive results. Moreover, the low isoelectric point
      of calreticulin and its chaperone properties may give rise to false-positive
      results under low stringency conditions. We report that the use of a simple
      buffer without protein (50 mM Tris, pH 7.5, 1% Tween 20, 0.3 M NaCl) removes most
      of the problems with unwanted binding (high stringency conditions). Using the
      high stringency conditions, we screened sera from 107 patients with systemic
      lupus erythematosus, sera from patients with other systemic autoimmune diseases
      and from children with coeliac disease for the presence of high-affinity
      calreticulin autoantibodies by immunoblotting and ELISA. None of the sera
      contained high-affinity calreticulin antibodies. It is concluded that
      calreticulin is not a common autoantigen in patients with autoimmune connective
      tissue diseases or coeliac disease.

PMID- 16081364
TI  - Urinary 6-hydroxymelatonin sulfate excretion in intellectually disabled subjects
      with sleep disorders and multiple medications: validation of measurements in
      urine extracted from diapers.
AB  - The aim of this study was to examine the applicability of urinary 6
      hydroxymelatonin sulfate (MT6s) measurements in the evaluation of melatonin
      secretion in intellectually disabled patients with sleep disorders. All 17
      patients received drugs with potential interactions with melatonin metabolism.
      Serum melatonin 24-h profiles were determined at hourly intervals. The area under
      the curve (AUC) value, peak amplitude, half-rise time, and half-decline time were
      calculated individually. Urinary MT6s excretion was determined from samples
      collected from disposable diapers during three consecutive days at varying
      intervals. The average excretion rate for each hour of the day was calculated.
      The excretion profiles were characterized by total amount of MT6s excretion/24
      h/kg body mass, amount of excreted MT6s during 6 h of maximum excretion (MAX 6h),
      and start time of the maximum excretion (start MAX 6h). There were significant
      positive correlations between serum melatonin AUC value and total excretion of
      MT6s/body mass, between serum melatonin amplitude and urinary MAX 6h, and between
      melatonin half-rise time and start MAX 6h; one patient on phenobarbital
      medication was out of line. The serum melatonin profiles of the patients were
      classified by comparing them with those of matched healthy volunteers (low-,
      normal-, or high secretors, normal or delayed rhythm). Similarly, the parameters
      of MT6s profiles were compared with those obtained from healthy controls, and the
      patients were reclassified as normal or aberrant. The classifications based on
      serum melatonin and urinary MT6s measurements were mostly concordant. The daily
      pattern of urinary MT6s excretion reliably reflected the phase of the serum
      melatonin rhythm irrespective of the medications, but in some cases, the total
      amount of excreted MT6s was lower than expected based on serum melatonin
      measurements.

PMID- 16081365
TI  - Long-term stability of salivary cortisol.
AB  - The measurement of salivary cortisol provides a simple, non-invasive, and stress
      free measure frequently used in studies of the hypothalamic-pituitary-adrenal
      axis activity. In research projects, samples are often required to be stored for
      longer periods of time either because of the protocol of the project or because
      of lack of funding for analysis. The aim of the present study was to explore the
      effects of long-term storage of samples on the amounts of measurable cortisol.
      Ten pools of saliva were collected on polyester Salivette tampons from five
      subjects. After centrifugation the samples were either stored in small vials or
      spiked to polyester Salivette tampons before analysis for cortisol using Spectria
      RIA kits. The effects of storage were evaluated by a linear regression model
      (mixed procedure) on a logarithmic scale. No effects on cortisol concentrations
      were found after storage of saliva at 5 degrees C for up to 3 months or at -20
      degrees C and -80 degrees C for up to one year. In contrast, concentrations of
      cortisol were found to decrease by 9.2% (95% confidence interval (CI): 3.8%;
      14.3%) per month in samples stored at room temperature. Repeated freezing and
      thawing of samples up to four times before analysis did not affect the measured
      concentrations of cortisol. The coefficient of residual variation (CVresid) for
      samples stored on Salivette tampons were twice the CVresid for samples stored in
      separate vials after centrifugation. In conclusion, centrifuged saliva samples
      for analysis of cortisol may be stored at 5 degrees C for up to 3 months or at 
      20 degrees C or -80 degrees C for at least one year. However, long-term storage
      at room temperature cannot be recommended. Repeated cycles of freezing and
      thawing did not appear to affect the concentrations of cortisol.

PMID- 16081366
TI  - The insulin gene in type 1 diabetes.
AB  - Insulin is a key autoantigen in the autoimmune process leading to the development
      of type 1 diabetes. Recent studies in both humans and mice have shown that
      variation in the expression of the insulin gene, in the thymus rather than the
      pancreas, contributes to disease susceptibility by affecting self-tolerance to
      insulin. These findings have brought about a paradigm-shift in our understanding
      of self-tolerance and autoimmunity to molecules with tissue-restricted
      expression, which are often the target of autoimmune disease.

PMID- 16081367
TI  - Protein splicing mechanisms and applications.
AB  - Inteins are protein splicing elements that employ standard enzyme strategies to
      excise themselves from precursor proteins and ligate the surrounding sequences
      (exteins). The protein splicing pathway consists of four nucleophilic
      displacements directed by the intein plus the first C-extein residue. The intein
      active site(s) are formed by folding of the intein within the precursor, which
      brings together the splice junctions and internal intein residues that assist
      catalysis. Inteins with non-canonical catalytic residues splice by modified
      pathways. Understanding intein proteolytic cleavage and ligation activities has
      led to the development of many novel applications in the fields of protein
      engineering, enzymology, microarray production, target detection and activation
      of transgenes in plants. Recent advances include intein-mediated attachment of
      proteins to solid supports for microarray or western blot analysis, linking
      nucleic acids to proteins and controllable splicing, which converts inteins into
      molecular switches.

PMID- 16081368
TI  - The ganglioside GD3 as the Greek goddess Hecate: several faces turned towards as
      many directions.
AB  - The disialoganglioside GD3 can mediate biological functions as diverse as
      proliferation, differentiation, and apoptosis. Since intracellular level of GD3
      is crucial for the cell, understanding the mechanisms by which GD3 metabolism is
      tightly regulated seems of particular importance. GD3 can be enlisted among the
      most potent natural inducers of mitochondrial damage and apoptosis. However, some
      cell types resist GD3-mediated mitochondrial damage through complex mechanisms
      which are beginning to be unveiled.

PMID- 16081369
TI  - Nuclear hormone receptor degradation and gene transcription: an update.
AB  - The ubiquitin-proteasome pathway (UPP) is known to degrade short-lived and
      misfolded proteins. Its role in cell cycle regulation and signal transduction is
      well established. However, the importance of the UPP in nuclear hormone receptor
      regulated gene transcription is relatively new. Nuclear hormone receptors (NHRs)
      are degraded by the UPP both in the presence or absence of their cognate ligands.
      In recent years, it has become evident that NHR degradation and NHR-dependent
      transcription are interdependent processes. The link between these two processes
      has become stronger with the discovery of a number of ubiquitin-pathway enzymes
      and components of the proteasome acting as modulators of NHR function. Also, UPP
      enzymes and components of the proteasome are recruited to the promoters of NHR
      responsive genes. Interestingly both coactivators and corepressors (coregulators)
      of NHRs are also targeted to the UPP for degradation. Furthermore, additional
      evidence also indicates that the UPP may be involved in the turnover of
      transcription complexes, thereby facilitating proper gene transcription. In this
      review we discuss and provide an update on the role of UPP in NHR-dependent gene
      regulation.

PMID- 16081370
TI  - Binding of the coenzyme and formation of the transketolase active center.
AB  - Transketolase (TK) is a homodimer, the simplest representative of thiamine
      diphosphate (ThDP)-dependent enzymes. It was first ThDP-dependent enzymes the
      crystal structure of which has been solved and revealed the general fold for this
      class of enzymes and the interactions of the non-covalently bound coenzyme ThDP
      with the protein component. Transketolase is a convenient model to study the
      structure(s) of the active center and the mechanism of action of ThDP-dependent
      enzymes. This review summarizes the results of studies on the kinetics of the
      interaction of ThDP with TK from Saccharomyces cerevisiae as well as the
      generation of the catalytically active form of the coenzyme within the holoenzyme
      and formation of the enzyme's active center.

PMID- 16081371
TI  - Systemic regulation of intestinal iron absorption.
AB  - The intestinal absorption of the essential trace element iron and its
      mobilization from storage sites in the body are controlled by systemic signals
      that reflect tissue iron requirements. Recent advances have indicated that the
      liver-derived peptide hepcidin plays a central role in this process by repressing
      iron release from intestinal enterocytes, macrophages and other body cells. When
      iron requirements are increased, hepcidin levels decline and more iron enters the
      plasma. It has been proposed that the level of circulating diferric transferrin,
      which reflects tissue iron levels, acts as a signal to alter hepcidin expression.
      In the liver, the proteins HFE, transferrin receptor 2 and hemojuvelin may be
      involved in mediating this signal as disruption of each of these molecules
      decreases hepcidin expression. Patients carrying mutations in these molecules or
      in hepcidin itself develop systemic iron loading (or hemochromatosis) due to
      their inability to down regulate iron absorption. Hepcidin is also responsible
      for the decreased plasma iron or hypoferremia that accompanies inflammation and
      various chronic diseases as its expression is stimulated by pro-inflammatory
      cytokines such as interleukin 6. The mechanisms underlying the regulation of
      hepcidin expression and how it acts on cells to control iron release are key
      areas of ongoing research.

PMID- 16081372
TI  - Membrane protein solubilization: recent advances and challenges in solubilization
      of serotonin1A receptors.
AB  - Solubilization of integral membrane proteins is a process in which the proteins
      and lipids that are held together in native membranes are suitably dissociated in
      a buffered detergent solution. The controlled dissociation of the membrane
      results in formation of small protein and lipid clusters that remain dissolved in
      the aqueous solution. Effective solubilization and purification of membrane
      proteins, especially heterologously-expressed proteins in mammalian cells in
      culture, in functionally active forms represent important steps in understanding
      structure-function relationship of membrane proteins. In this review, critical
      factors determining functional solubilization of membrane proteins are
      highlighted with the solubilization of the serotonin 1A receptor taken as a
      specific example.

PMID- 16081373
TI  - Adaptive evolution after gene duplication in alpha-KT x 14 subfamily from Buthus
      martensii Karsch.
AB  - A series of isoforms of alpha-KT x 14 (short chain potassium channel scorpion
      toxins) were isolated from the venom of Buthus martensii Karsch by RACE and
      screening cDNA library methods. These isoforms adding BmKK1--3 and BmSKTx1--2
      together shared high homology (more than 97%) with each other. The result of
      genomic sequence analysis showed that a length 79 bp intron is inserted Ala codes
      between the first and the second base at the 17th amino acid of signal peptide.
      The introns of these isoforms also share high homology with those of BmKK2 and
      BmSKT x 1 reported previously. Sequence analysis of many clones of cDNA and
      genomic DNA showed that a species population or individual polymorphism of alpha
      KT x 14 genes took place in scorpion Buthus martensii Karsch and accelerated
      evolution played an important role in the forming process of alpha-KT x 14
      scorpion toxins subfamily. The result of southern hybridization indicated that
      alpha-KT x 14 toxin genes existed in scorpion chromosome with multicopies. All
      findings maybe provided an important evidence for an extensive evolutionary
      process of the scorpion "pharmacological factory": at the early course of
      evolution, the ancestor toxic gene duplicated into a series of multicopy genes
      integrated at the different chromosome; at the late course of evolution,
      subsequent functional divergence of duplicate genes was generated by mutations,
      deletions and insertion.

PMID- 16081374
TI  - Is there an answer?

PMID- 16081375
TI  - Textbook horrors: DNA horrors.

PMID- 16081387
TI  - Therapist sensitivity towards emotional life-career issues and the working
      alliance with suicide attempters.
AB  - This study investigated the usefulness of an action theoretical model of suicide
      in interviewing suicide attempters. Eighteen interviews were video-recorded and
      transcribed. The patients' narratives were reconstructed and life-career issues
      relevant for the patient's suicidality formulated. Skin conductance response was
      used to determine narrative content associated with actualized emotions. Scores
      of the patients' ratings of helping alliance experienced in the interview were
      positively associated with the therapists' sensitivity towards emotionally
      relevant life-career issues. Furthermore, relationship satisfaction was related
      to a narrative interviewing style. We conclude that working alliance in clinical
      interviews with suicide attempters can be improved when the interviewer uses a
      patient-oriented approach aimed at understanding the patient's suicidality in the
      context of personal life-career, or identity issues.

PMID- 16081388
TI  - Pain and psychiatric disorders contribute independently to suicidal ideation in
      HIV-positive persons.
AB  - The relationships between HIV-related pain, psychiatric disorders, and suicidal
      ideation (SI) are not well understood. The presented research investigated the
      ability of pain, psychiatric diagnoses, coping styles, and locus of control (LOC)
      to predict SI in 75 HIV-positive persons, using a sequential logistic regression.
      Reported psychiatric diagnoses included depression, anxiety, and substance abuse
      disorders. Variance accounted for by these analyses was approximated at 33%, with
      pain severity independently predicting SI after accounting for psychiatric
      diagnoses. Coping and LOC did not add significantly to the models. Given the
      prevalence of pain in this population, these results underscore the importance of
      assessing and treating pain and SI in persons with HIV.

PMID- 16081389
TI  - Personal and family risk factors for adolescent suicidal ideation and attempts.
AB  - Despite research indicating that suicidal ideation is strongly related to future
      suicide attempts, there is limited data on variables associated with continued
      suicidal ideation and behaviors in adolescents. The objective of this study is to
      investigate whether personal, cognitive and family risk factors can differentiate
      adolescent suicidal ideation and attempts. Twenty-four attempters, 50 ideators
      and 50 non-suicidal adolescents (aged 14 to 25 years) were asked during an
      interview to complete individual and psychosocial measures. Both suicidal groups
      reported greater personal vulnerability and perceived their family as less
      functional than did the non-suicidal group. However, no differences were found
      between both suicidal groups. The results suggest the presence of common factors
      in both adolescent suicidal ideators and attempters.

PMID- 16081390
TI  - Depression, anxiety, and psychological defense in attempted suicide: a pilot
      study using PORT.
AB  - Depressive affect, anxiety, and psychological defenses were studied in the
      presented research with PORT, a projective test that exploits subliminal
      perception of object-relation images. Protocols of 20 hospitalized suicide
      attempters were compared to those of 20 matched controls, 34 previously studied
      nonsuicidal depressed patients, 18 patients with panic attack, and 32 patients
      with borderline and psychotic disorders. The suicide attempters were anxious;
      their defenses resembled those seen in borderline pathology; depressive reactions
      were limited in symbolic content; reality testing was poor. The closeness between
      depression and anxiety in suicidality is further discussed throughout this
      article. A constellation of signs using the PORT test was hypothesized to be a
      marker for suicidality. The test is deemed useful for future research on suicide.

PMID- 16081391
TI  - Children's reasons for living, self-esteem, and violence.
AB  - Attitudes toward violence and reasons for living in young adolescents with high,
      moderate, and low self-esteem were examined. The authors devised an Attitudes
      Toward Violence questionnaire; the Rosenberg's Self-esteem Scale (RSE) and the
      Brief Reasons for Living in Adolescents (BRFL-A) was used to assess adaptive
      characteristics. The independent variables were gender and self-esteem. The
      dependent variables were total Reasons for Living score and Attitudes Toward
      Violence score. Participants included 138 boys and 95 girls, ages 11 to 15 years
      (M = 13.3) from a city middle school. The results showed that for the dependent
      variable attitudes toward violence, main effects were found for both gender and
      self-esteem. For the dependent variable reasons for living, a main effect was
      found for self-esteem but not for gender. An inverse relationship was found
      between violence and reasons for living. Being male and low self-esteem emerged
      as predictors of more accepting attitudes toward violence. Low self-esteem was
      significantly related to fewer reasons for living.

PMID- 16081392
TI  - Can suicides be identified from case records? A case control study using blind
      rating.
AB  - A majority of case control studies of suicide risks in psychiatric patients
      reveal an excess of risk factors in cases. None of the case control studies has
      been conducted blind to case identity. The present study examined the possibility
      that skilled clinicians could identify suicides blind from case records of last
      episode of care. Records of 39 suicides of psychiatric patients and their matched
      controls (N = 78) were abstracted blind and dichotomously rated for suicide by
      seven raters. Success in identification of cases approximated to chance
      expectation. Pending replication, these disappointing findings call in question
      the clinical utility of risk factor findings to date, their validity as a basis
      for significant change in service provision and the medico-legal significance of
      records in suicide-related civil law suits.

PMID- 16081393
TI  - The culture of suicide through societal integration and religion: 1996-1998
      gender-specific suicide rates in 50 American states.
AB  - A multivariate model of 1996-1998 male and female suicide rates in the 50 states
      using Durkheim's societal integration concepts, spatial integration, and the
      culture of suicide was the focus of our research. Using multiple regression
      analysis, state divorce rates, church membership, approval of suicide, sex
      ratios, population density, and lagged 1981-82 suicide rates appeared to be
      statistically significant, which explained 90 percent of male and 79 percent of
      female suicide rate variation. Previous reports based on the hypothesis that
      western states have high suicide rates due to the high suicide rates of Native
      Americans residing in the West was rejected, as was the second hypothesis that
      the high western rates are due to higher western than non-western use of firearms
      in suicide. The usefulness of macro-level predictors of suicide rates was
      discussed and we concluded that macro-level analysis was needed to explain trends
      in suicide, to understand differences in suicide levels among states and nations,
      as well as differences in the age structures of suicide among populations.

PMID- 16081394
TI  - Suicide risk among physicians: a multivariate analysis.
AB  - It has been hypothesized that previous research on physician suicide has
      neglected a possible suppressor effect on suicide from a low risk of divorce
      among physicians. The present article addresses this question using data on
      143,885 deaths from the 1990 National Mortality Detail Files. The results of a
      multivariate logistic regression analysis indicated that when controls are
      introduced for marital status, gender, race, and other covariates of social
      status, physicians were 2.45 times more likely to die of suicide than the rest of
      the working age population. The results suggested that previous work, which had
      not controlled for the protective effect of marital status, might have
      underestimated the incidence of physician suicide.

PMID- 16081396
TI  - Neither altruistic suicide, nor terrorism but martyrdom: a Muslim perspective.

PMID- 16081397
TI  - Suicide genes floating in a glass of sparkling wine.
AB  - The presented commentary will tackle the genetics behind suicidal behavior. The
      phenotype is defined followed by a brief discussion of two employable genetic
      methods, namely, positional cloning and the more classical approach involving
      candidate genes. Furthermore, we will explain the polygenetic, multi-factorial
      model of suicidal genetics and address the interaction of genes and the
      environment. Further along we list possible ways in which suicidal behavior could
      have been selected for genetically in populations and identify those specific
      populations in which it may have appeared. Finally, we address future ethical
      implications in this quickly blossoming field of research.

PMID- 16081398
TI  - Geographic variation in suicide rates: relationships to social factors,
      migration, and ethnic history.
AB  - Geographic variation in suicide rates is thought to be the result of interactions
      between two major components: the social organization combined with cultural
      tradition and biological or genetic factors. The present study examined regional
      patterns of suicide rates in European Russia. Our study looked at ethnic and
      national formations with respect to suicide patterns. The results indicated that
      the suicide rates vary greatly among the regions of the Russian Federation, with
      suicides more common in the northern regions of European Russia than in the south
      of the country. The south and north gradient of suicide distributions in Russia
      resemble that of other European countries. Throughout the Middle ages the north
      and northwest territory of present-day Russia has been an area of intensive
      interethnic contacts between the Old Slavs, which have colonized this territory,
      and native people of Finno-Ugrian and Baltic origin. The results indicated that
      the historical prevalence of the Finno-Ugrian component in the north of the
      country has possibly led to its higher suicide rate.

PMID- 16081399
TI  - The use of mindfulness-based approaches for suicidal patients.
AB  - Mindfulness-based approaches are becoming more widely used for individuals at
      risk of suicidal behavior: in the treatment of borderline personality disorder
      (in Dialectical Behavior Therapy), and as a way to reduce relapse in recurrent
      major depression (in Mindfulness-based Cognitive Therapy). This article describes
      and examines the commonalities and differences in the use of mindfulness in these
      two treatments. The reasons for considering the use of mindfulness-based
      approaches with suicidal individuals more widely are considered and potential
      risks outlined. The article closes with case examples to illustrate the use of
      mindfulness in the treatment of suicidal thoughts and behaviors.

PMID- 16081400
TI  - Benefits of implementing an academic training of trainers program to promote
      knowledge and clarity in work with psychiatric suicidal patients.
AB  - A 200-hour academic, postgraduate training-of-trainers program in suicide
      prevention at Karolinska Institute for key mental healthcare staff, designed to
      enable them to enhance their co-workers' knowledge and job clarity, was evaluated
      in a panel study by means of questionnaires. Psychiatric staff working regularly
      with suicidal patients in clinics where key persons attended the course (n = 134,
      intervention group) were compared with staff working in clinics without
      participants (n = 166, control group). Perceptions of being sufficiently trained
      (p < .01) improved significantly among staff working in intervention clinics.
      Compared with the control group, the intervention group had a better
      understanding of essentials (p < .05); found instructions clearer (p < .01) and
      experienced fewer problems with superiors' differing views (p < .05) at follow
      up. Assistant nurses working in intervention clinics seem to have benefited most.

PMID- 16081401
TI  - The general public's views on suicide and suicide prevention, and their
      perception of participating in a study on attitudes towards suicide.
AB  - The aim of the presented study was to investigate whether common myths about
      suicide still prevail, what people in general think are the most common causes
      for suicide, whether suicide can be prevented, and if so, how. How subjects
      perceived their participation in a study on attitudes towards suicidal behavior,
      was also investigated. The Attitudes Towards Suicide questionnaire was sent to a
      random sample of 1,000 Norwegians. The data were analyzed both quantitatively and
      qualitatively. The results showed that the common myths still prevail, that
      people in general mainly assign intrapersonal causes to suicide, with the belief
      that suicide can be prevented, and that they perceived their participation in the
      study positively. The value of the general public in suicide prevention and the
      need for increased openness and competence building were emphasized.

PMID- 16081402
TI  - Gun control and suicide: possible impact of Canadian legislation to ensure safe
      storage of firearms.
AB  - In 1992, the Canadian Firearms Act aimed at ensuring safe storage of firearms was
      promulgated. This study compares suicide methods 6 years prior to the enactment
      of the law and 5 years after its enactment. The study encompassed 426 suicide
      cases from Abitibi-Temiscamingue (Northern Quebec), the region with the highest
      suicide rate and the highest firearm suicide rate in Quebec. Suicide by firearms
      decreased in the male and female population. Suicide by hanging increased among
      youths of both sexes, and suicide by poisoning doubled in the female population.
      A decrease in firearm suicides was most noticeable in the under-25 age group,
      although it was in this same age group that the general suicide rate increased
      the most. The reduction of firearm suicides was not accompanied by a decrease in
      overall suicide rates.

PMID- 16081403
TI  - Impulsivity in drug dependent patients who attempt suicide.
AB  - Impulsivity is a personality dimension often implicated in suicidal behavior.
      However, it has been little studied in drug dependent patients who attempt
      suicide. Therefore, 292 recently abstinent opiate or cocaine dependent patients
      were asked to complete the Barratt Impulsivity Scale (BIS). Those who had
      attempted suicide were compared with those who had never attempted suicide for
      their scores on the BIS. The results showed that there was no significant
      difference between the drug dependent patients who had attempted suicide (N = 91)
      and those who had never attempted suicide (N = 201) on BIS scores. The possible
      clinical implication may be that the high impulsivity associated with drug
      dependent patients may mitigate the utility of impulsivity in the suicide risk
      assessment of such patients.

PMID- 16081404
TI  - Suicide among social workers: a research note.
AB  - Occupations have been a relatively neglected risk factor in the etiology of
      suicide. Client-oriented occupations are often thought to contribute to suicide
      by increasing psychological stress. The present study tests this thesis for the
      case of social work. Data were collected from 21 reporting states in the year of
      1990. Controls are introduced for possible covariates of social work including
      gender, race, region, age, and marital status. The results of a preliminary
      logistic regression analysis found that being a social worker increased the odds
      of death by suicide by 55.6%, compared to the rest of the working age population.
      However, when controls for other occupations were incorporated into the analysis,
      social workers were no longer at elevated odds of death by suicide relative to
      other professional-managerial occupations. The psychological resources and
      training of social workers may act as buffers against occupational stress. Being
      Caucasian, male, younger, and being non-married all increased the odds of death
      by suicide.

PMID- 16081405
TI  - Suicide in Lithuania during the years of 1990 to 2002.
AB  - Lithuania, among other Eastern European countries, has the highest suicide rates
      in the world. While the mid 1980's experienced a sharp decline in suicidality,
      the year of 1991 began a new increase in suicide rates, reaching an estimated
      44.7 per 100,000 persons in the year of 2002. The ratio of male to female rates
      was 4.5 to 6.1 in the years of 1990 to 2002. The suicide mortality of rural
      inhabitants, especially men, has been growing even more intensely, occurring
      twice as often as among their urban counterparts. When looking at the age factor,
      the highest suicide risk is for middle-aged men. Among the males aged 45 to 54
      years suicide rates reach 154.6. The most common method of suicide remains
      hanging, both for males and females. The underlying reasons of the suicide spread
      in Lithuania are multi determined.

PMID- 16081408
TI  - Proteomics-based identification of human acute leukemia antigens that induce
      humoral immune response.
AB  - The identification of panels of tumor antigens that elicit an antibody response
      may have utility in cancer screening, diagnosis, and establishing prognosis.
      Until now, autoimmunity in cancer has been mainly revealed in solid tumors. The
      aim of this study was to apply the proteomic approach to the identification of
      proteins that commonly elicit a humoral response in acute leukemia (AL). Sera
      from 21 newly diagnosed patients with AL, 20 patients with solid tumors, and 22
      noncancer controls were analyzed for antibody-based reactivity against AL
      proteins resolved by two-dimensional electrophoresis. As a result, autoantibody
      against a protein identified by mass spectrometry as Rho GDP dissociation
      inhibitor 2 was detected in sera from 15 of 21 patients with AL (71%). By
      contrast, such antibody was detected in sera from one of 20 patients with solid
      tumors (5%) and one of 22 noncancer controls (4.5%). Five other protein
      autoantibodies were also found in AL patients with a high frequency and
      constituted the major target antigens of the AL autoimmune response. The findings
      of autoantibodies against Rho GDP dissociation inhibitor 2 and other proteins in
      sera of patients with AL suggest that the proteomic approach we have implemented
      may have utility for the development of a serum-based assay for AL screening and
      diagnosis.

PMID- 16081409
TI  - The human platelet membrane proteome reveals several new potential membrane
      proteins.
AB  - We present the first focused proteome study on human platelet membranes. Due to
      the removal of highly abundant cytoskeletal proteins a wide spectrum of known
      platelet membrane proteins and several new and hypothetical proteins were
      accessible. In contrast to other proteome studies we focused on prefractionation
      and purification of membranes from human platelets according to published
      protocols to reduce sample complexity and enrich interesting membrane proteins.
      Subsequently protein separation by common one-dimensional SDS-PAGE as well as the
      combined benzyldimethyl-n-hexadecylammonium chloride/SDS separation technique was
      performed prior to mass spectrometry analysis by nano-LC-ESI-MS/MS. We
      demonstrate that the application of both separation systems in parallel is
      required for maximization of protein tagging out of a complex sample. Furthermore
      the identification of several potential membrane proteins in human platelets
      yields new potential targets in functional platelet research.

PMID- 16081410
TI  - Chemical genetic engineering of G protein-coupled receptor kinase 2.
AB  - G protein-coupled receptor kinases (GRKs) play a pivotal role in receptor
      regulation. Efforts to study the acute effects of GRKs in intact cells have been
      limited by a lack of specific inhibitors. In the present study we have developed
      an engineered version of GRK2 that is specifically and reversibly inhibited by
      the substituted nucleotide analog 1-naphthyl-PP1 (1Na-PP1), and we explored GRK2
      function in regulated internalization of the mu-opioid receptor (muOR). A
      previously described method that conferred analog sensitivity on various kinases,
      by introducing a space-creating mutation in the conserved active site, failed
      when applied to GRK2 because the corresponding mutation (L271G) rendered the
      mutant kinase (GRK2-as1) catalytically inactive. A sequence homology-based
      approach was used to design second-site suppressor mutations. A C221V second-site
      mutation produced a mutant kinase (GRK2-as5) with full functional activity and
      analog sensitivity as compared with wild-type GRK2 in vitro and in intact cells.
      The role of GRK2-as5 activity in the membrane trafficking of the muOR was also
      characterized. Morphine-induced internalization was completely blocked when GRK2
      as5 activity was inhibited before morphine application. However, inhibition of
      GRK2-as5 during recycling and reinternalization of the muOR did not attenuate
      these processes. These results suggest there is a difference in the GRK
      requirement for initial ligand-induced internalization of a G protein-coupled
      receptor compared with subsequent rounds of reinternalization.

PMID- 16081411
TI  - Endogenous unsaturated C18 N-acylethanolamines are vanilloid receptor (TRPV1)
      agonists.
AB  - The endogenous C18 N-acylethanolamines (NAEs) N-linolenoylethanolamine (18:3
      NAE), N-linoleoylethanolamine (18:2 NAE), N-oleoylethanolamine (18:1 NAE), and N
      stearoylethanolamine (18:0 NAE) are structurally related to the endocannabinoid
      anandamide (20:4 NAE), but these lipids are poor ligands at cannabinoid CB(1)
      receptors. Anandamide is also an activator of the transient receptor potential
      (TRP) vanilloid 1 (TRPV(1)) on primary sensory neurons. Here we show that C18
      NAEs are present in rat sensory ganglia and vascular tissue. With the exception
      of 18:3 NAE in rat sensory ganglia, the levels of C18 NAEs are equal to or
      substantially exceed those of anandamide. At submicromolar concentrations, 18:3
      NAE, 18:2 NAE, and 18:1 NAE, but not 18:0 NAE and oleic acid, activate native
      rTRPV(1) on perivascular sensory nerves. 18:1 NAE does not activate these nerves
      in TRPV(1) gene knock-out mice. Only the unsaturated C18 NAEs elicit whole cell
      currents and fluorometric calcium responses in HEK293 cells expressing hTRPV(1).
      Molecular modeling revealed a low energy cluster of U-shaped unsaturated NAE
      conformers, sharing several pharmacophoric elements with capsaicin. Furthermore,
      one of the two major low energy conformational families of anandamide also
      overlaps with the cannabinoid CB(1) receptor ligand HU210, which is in line with
      anandamide being a dual activator of TRPV(1) and the cannabinoid CB(1) receptor.
      This study shows that several endogenous non-cannabinoid NAEs, many of which are
      more abundant than anandamide in rat tissues, activate TRPV(1) and thus may play
      a role as endogenous TRPV(1) modulators.

PMID- 16081412
TI  - Arabidopsis AtDGK7, the smallest member of plant diacylglycerol kinases (DGKs),
      displays unique biochemical features and saturates at low substrate
      concentration: the DGK inhibitor R59022 differentially affects AtDGK2 and AtDGK7
      activity in vitro and alters plant growth and development.
AB  - Diacylglycerol kinase (DGK) regulates the level of the second messenger
      diacylglycerol and produces phosphatidic acid (PA), another signaling molecule.
      The Arabidopsis thaliana genome encodes seven putative diacylglycerol kinase
      isozymes (named AtDGK1 to -7), structurally falling into three major clusters. So
      far, enzymatic activity has not been reported for any plant Cluster II DGK. Here,
      we demonstrate that a representative of this cluster, AtDGK7, is biochemically
      active when expressed as a recombinant protein in Escherichia coli. AtDGK7,
      encoded by gene locus At4g30340, contains 374 amino acids with an apparent
      molecular mass of 41.2 kDa. AtDGK7 harbors an N-terminal catalytic domain, but in
      contrast to various characterized DGKs (including AtDGK2), it lacks a cysteine
      rich domain at its N terminus, and, importantly, its C-terminal DGK accessory
      domain is incomplete. Recombinant AtDGK7 expressed in E. coli exhibits Michaelis
      Menten type kinetics with 1,2-dioleoyl-sn-glycerol as substrate. AtDGK7 activity
      was affected by pH, detergents, and the DGK inhibitor R59022. We demonstrate that
      both AtDGK2 and AtDGK7 phosphorylate diacylglycerol molecular species that are
      typically found in plants, indicating that both enzymes convert physiologically
      relevant substrates. AtDGK7 is expressed throughout the Arabidopsis plant, but
      expression is strongest in flowers and young seedlings. Expression of AtDGK2 is
      transiently induced by wounding. R59022 at approximately 80 mum inhibits root
      elongation and lateral root formation and reduces plant growth, indicating that
      DGKs play an important role in plant development.

PMID- 16081414
TI  - The EAL domain protein VieA is a cyclic diguanylate phosphodiesterase.
AB  - The newly recognized bacterial second messenger 3',5'-cyclic diguanylic acid
      (cyclic diguanylate (c-di-GMP)) has been shown to regulate a wide variety of
      bacterial behaviors and traits. Biosynthesis and degradation of c-di-GMP have
      been attributed to the GGDEF and EAL protein domains, respectively, based
      primarily on genetic evidence. Whereas the GGDEF domain was demonstrated to
      possess diguanylate cyclase activity in vitro, the EAL domain has not been tested
      directly for c-di-GMP phosphodiesterase activity. This study describes the
      analysis of c-di-GMP hydrolysis by an EAL domain protein in a purified system.
      The Vibrio cholerae EAL domain protein VieA has been shown to inversely regulate
      biofilm-specific genes (vps) and virulence genes (ctxA), presumably by decreasing
      the cellular pool of c-di-GMP. VieA was maximally active at neutral pH,
      physiological ionic strength, and ambient temperatures and demonstrated c-di-GMP
      hydrolytic activity with a Km of 0.06 microM. VieA was unable to hydrolyze cGMP.
      The putative metal coordination site of the EAL domain, Glu170, was demonstrated
      to be necessary for VieA activity. Furthermore, the divalent cations Mg2+ and
      Mn2+ were necessary for VieA activity; conversely, Ca2+ and Zn2+ were potent
      inhibitors of the VieA phosphodiesterase. Calcium inhibition of the VieA EAL
      domain provides a potential mechanism for regulation of c-di-GMP degradation.

PMID- 16081413
TI  - Menkes Copper ATPase (Atp7a) is a novel metal-responsive gene in rat duodenum,
      and immunoreactive protein is present on brush-border and basolateral membrane
      domains.
AB  - We previously noted strong induction of genes related to intestinal copper
      homeostasis (Menkes Copper ATPase (Atp7a) and metallothionein) in the duodenal
      epithelium of iron-deficient rats across several stages of postnatal development
      (Collins, J. F., Franck, C. A., Kowdley, K. V., and Ghishan, F. K. (2005) Am. J.
      Physiol., 288, G964-G971). We now report significant copper loading in the livers
      and intestines of iron-deficient rats. These findings are consistent with the
      hypothesis that there is increased intestinal copper transport during iron
      deficiency. We additionally found that hepatic Atp7b gene expression does not
      change with iron deficiency, suggesting that liver copper excretion is not
      altered. We have developed polyclonal antibodies against rat ATP7A, and we
      demonstrate the specificity of the immunogenic reaction. We show that the ATP7A
      protein is present on apical domains of duodenal enterocytes in control rats and
      on brush-border and basolateral membrane domains in iron-deprived rats. This
      localization is surprising, as previous in vitro studies have suggested that
      ATP7A traffics between the trans-Golgi network and the basolateral membrane. We
      further demonstrate that ATP7A protein levels are dramatically increased in brush
      border and basolateral membrane vesicles isolated from iron-deficient rats. Other
      experiments show that iron refeeding partially corrects the hematological
      abnormalities seen in iron-deficient rats but that it does not ameliorate ATP7A
      protein induction, suggesting that Atp7a does not respond to intracellular iron
      levels. We conclude that ATP7A is involved in copper loading observed during iron
      deficiency and that increased intestinal copper transport is of physiological
      relevance, as copper plays important roles in overall body iron homeostasis.

PMID- 16081415
TI  - SIRPbeta1 is expressed as a disulfide-linked homodimer in leukocytes and
      positively regulates neutrophil transepithelial migration.
AB  - Signal regulatory proteins (SIRPs) comprise a family of cell surface signaling
      receptors differentially expressed in leukocytes and the central nervous system.
      Although the extracellular domains of SIRPs are highly similar, classical motifs
      in the cytoplasmic or transmembrane domains distinguish them as either activating
      (beta) or inhibitory (alpha) isoforms. We reported previously that human
      neutrophils (polymorphonuclear leukocytes (PMN)) express multiple SIRP isoforms
      and that SIRPalpha binding to its ligand CD47 regulates PMN transmigration. Here
      we further characterized the expression of PMN SIRPs, and we reported that the
      major SIRPalpha and SIRPbeta isoforms expressed in PMN include Bit/PTPNS-1 and
      SIRPbeta1, respectively. Furthermore, although SIRPalpha (Bit/PTPNS-1) is
      expressed as a monomer, we showed that SIRPbeta1 is expressed on the cell surface
      as a disulfide-linked homodimer with bond formation mediated by Cys-320 in the
      membrane-proximal Ig loop. Subcellular fractionation studies revealed a major
      pool of SIRPbeta1 within the plasma membrane fractions of PMN. In contrast, the
      majority of SIRPalpha (Bit/PTPNS-1) is present in fractions enriched in secondary
      granules and is translocated to the cell surface after chemoattractant
      (formylmethionylleucylphenylalanine) stimulation. Functional studies revealed
      that antibody-mediated ligation of SIRPbeta1 enhanced
      formylmethionylleucylphenylalanine-driven PMN transepithelial migration. Co
      immunoprecipitation experiments to identify associated adaptor proteins revealed
      a 10-12-kDa protein associated with SIRPbeta1 that was tyrosine-phosphorylated
      after PMN stimulation and is not DAP10/12 or Fc receptor gamma chain. These
      results provide new insights into the structure and function of SIRPs in
      leukocytes and their potential role(s) in fine-tuning responses to inflammatory
      stimuli.

PMID- 16081416
TI  - Identification of the minimal lysosomal enzyme recognition domain in cathepsin D.
AB  - Specific recognition of lysosomal hydrolases by UDP-GlcNAc:lysosomal enzyme N
      acetylglucosamine-1-phosphotransferase, the initial enzyme in the biosynthesis of
      mannose 6-phosphate residues, is governed by a common protein determinant.
      Previously, we generated a lysosomal enzyme recognition domain in the secretory
      protein glycopepsinogen by substituting in two regions (lysine 203 and amino
      acids 265-293 of the beta loop) from cathepsin D, a highly related lysosomal
      protease. Here we show that substitution of just two lysines (Lys-203 and Lys
      267) stimulates mannose phosphorylation 116-fold. Substitution of additional
      residues in the beta loop, particularly lysines, increased phosphorylation 4-fold
      further, approaching the level obtained with intact cathepsin D. All the
      phosphorylation occurred at the carboxyl lobe glycan, indicating that additional
      elements are required for phosphorylation of the amino lobe glycan. These data
      support the proposal that as few as two lysines in the correct orientation to
      each other and to the glycan can serve as the minimal elements of the lysosomal
      enzyme recognition domain. However, our findings show that the spacing between
      lysines is flexible and other residues contribute to the recognition marker.

PMID- 16081417
TI  - WNK1 activates SGK1 by a phosphatidylinositol 3-kinase-dependent and non
      catalytic mechanism.
AB  - WNK1 (with no lysine (K) 1) is a protein-serine/threonine kinase with a unique
      catalytic site organization. Deletions in the first intron of the WNK1 gene were
      found in a group of hypertensive patients with pseudohypoaldosteronism type II.
      No changes in coding sequence of WNK1 were found, but its expression was
      increased severalfold. We have been investigating actions of WNK1 and have found
      that WNK1 activates the serum- and glucocorticoid-induced protein kinase SGK1,
      which impacts membrane expression of the epithelial sodium channel. Here we
      explore the role of WNK1 in SGK1 regulation. Activation of SGK1 by WNK1 is
      blocked by phosphatidylinositol 3-kinase inhibitors. Neither the catalytic
      activity nor the kinase domain of WNK1 is required; rather the N-terminal 220
      residues of WNK1 are necessary and sufficient to activate SGK1. Phosphorylation
      of WNK1 on Thr-58 contributes to SGK1 activation. Finally, we show that WNK1 is
      required for the activation of SGK1 by insulin-like growth factor 1.

PMID- 16081418
TI  - Functionally diverse complement of large conductance calcium- and voltage
      activated potassium channel (BK) alpha-subunits generated from a single site of
      splicing.
AB  - The pore-forming alpha-subunits of large conductance calcium- and voltage
      activated potassium (BK) channels are encoded by a single gene that undergoes
      extensive alternative pre-mRNA splicing. However, the extent to which
      differential exon usage at a single site of splicing may confer functionally
      distinct properties on BK channels is largely unknown. Here we demonstrated that
      alternative splicing at site of splicing C2 in the mouse BK channel C terminus
      generates five distinct splice variants: ZERO, e20, e21(STREX), e22, and a novel
      variant deltae23. Splice variants display distinct patterns of tissue
      distribution with e21(STREX) expressed at the highest levels in adult endocrine
      tissues and e22 at embryonic stages of mouse development. deltae23 is not
      functionally expressed at the cell surface and acts as a dominant negative of
      cell surface expression by trapping other BK channel splice variant alpha
      subunits in the endoplasmic reticulum and perinuclear compartments. Splice
      variants display a range of biophysical properties. e21(STREX) and e22 variants
      display a significant left shift (>20 mV at 1 microM [Ca2+]i) in half-maximal
      voltage of activation compared with ZERO and e20 as well as considerably slower
      rates of deactivation. Splice variants are differentially sensitive to
      phosphorylation by endogenous cAMP-dependent protein kinase; ZERO, e20, and e22
      variants are all activated, whereas e21 (STREX) is the only variant that is
      inhibited. Thus alternative pre-mRNA splicing from a single site of splicing
      provides a mechanism to generate a physiologically diverse complement of BK
      channel alpha-subunits that differ dramatically in their tissue distribution,
      trafficking, and regulation.

PMID- 16081419
TI  - Deconvolution of a complex target using DNA aptamers.
AB  - In vitro selection of single-stranded nucleic acid aptamers from large random
      sequence libraries is now a straightforward process particularly when screening
      with a single target molecule. These libraries contain considerable shape
      diversity as evident by the successful isolation of aptamers that bind with high
      affinity and specificity to chemically diverse targets. We propose that aptamer
      libraries contain sufficient shape diversity to allow deconvolution of a complex
      mixture of targets. Using unfractionated human plasma as our experimental model,
      we aim to develop methods to obtain aptamers against as many proteins as
      possible. To begin, it is critical that we understand how aptamer populations
      change with increasing rounds of in vitro selection when using complex mixtures.
      Our results show that sequence representation in the selected population changes
      dramatically with increasing rounds of selection. Certain aptamer families were
      apparent after only three selection rounds. Two additional cycles saw a decline
      in the relative abundance of these families and the emergence of yet another
      family that accounted for more than 60% of sequences in the pool. To overcome
      this population convergence, an aptamer-based target depletion method was
      developed, and the library screen was repeated. The previous dominant family
      effectively disappeared from the selected populations but was replaced by other
      aptamer families. Insights gained from these initial experiments are now being
      applied in the creation of second generation plasma protein screens and also to
      the analysis of other complex biological targets.

PMID- 16081420
TI  - Omega-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral
      microvascular smooth muscle and endothelium by alcohol dehydrogenase 4.
AB  - 20-Carboxyeicosatetraenoic acid (20-COOH-AA) is a bioactive metabolite of 20
      hydroxyeicosatetraenoic acid (20-HETE), an eicosanoid that produces
      vasoconstriction in the cerebral circulation. We found that smooth muscle (MSMC)
      and endothelial (MEC) cultures obtained from mouse brain microvessels convert
      [3H]20-HETE to 20-COOH-AA, indicating that the cerebral vasculature can produce
      this metabolite. The [3H]20-COOH-AA accumulated primarily in the culture medium,
      together with additional radiolabeled metabolites identified as the chain
      shortened dicarboxylic acids 18-COOH-18:4, 18-COOH-18:3, and 16-COOH-16:3. N
      Heptylformamide, a potent inhibitor of alcohol dehydrogenase (ADH), decreased the
      conversion of [3H]20-HETE to 20-COOH-AA by the MSMC and MEC and also by isolated
      mouse brain microvessels. Purified mouse and human ADH4, human ADH3, and horse
      liver ADH1 efficiently oxidized 20-HETE, and ADH4 and ADH3 were detected in MSMC
      and MEC by Western blotting. N-Heptylformamide inhibited the oxidation of 20-HETE
      by mouse and human ADH4 but not by ADH3. These results demonstrated that cerebral
      microvessels convert 20-HETE to 20-COOH-AA and that ADH catalyzes the reaction.
      Although ADH4 and ADH3 are expressed in MSMC and MEC, the inhibition produced by
      N-heptylformamide suggests that ADH4 is primarily responsible for 20-COOH-AA
      formation in the cerebral microvasculature.

PMID- 16081421
TI  - Subtype-selective interaction with the transcription factor CCAAT/enhancer
      binding protein (C/EBP) homologous protein (CHOP) regulates cell surface
      expression of GABA(B) receptors.
AB  - The metabotropic gamma-aminobutyric acid, type B (GABA(B)) receptors mediate the
      slow component of GABAergic transmission in the brain. Functional GABA(B)
      receptors are heterodimers of the two subunits GABA(B1) and GABA(B2), of which
      GABA(B1) exists in two main isoforms, GABA(B1a) and GABA(B1b). The significance
      of the structural heterogeneity of GABA(B) receptors, the mechanism leading to
      their differential targeting in neurons as well as the regulation of cell surface
      numbers of GABA(B) receptors, is poorly understood. To gain insights into these
      processes, we searched for proteins interacting with the C-terminal domain of
      GABA(B2). Here, we showed that the transcription factor CCAAT/enhancer-binding
      protein (C/EBP) homologous protein (CHOP) directly interacts with GABA(B)
      receptors in a subtype-selective manner to regulate cell surface expression of
      GABA(B1a)/GABA(B2) receptors upon co-expression in HEK 293 cells. The interaction
      of CHOP with GABA(B1a)/GABA(B2) receptors resulted in their intracellular
      accumulation and in a reduced number of cell surface receptors. This regulation
      required the interaction of CHOP via two distinct domains with the heterodimeric
      receptor; its C-terminal leucine zipper associates with the leucine zipper
      present in the C-terminal domain of GABA(B2), and its N-terminal domain
      associates with an as yet unidentified site on GABA(B1a). In conclusion, the data
      indicated a subtype-selective regulation of cell surface receptors by interaction
      with the transcription factor CHOP.

PMID- 16081422
TI  - A functional role for the switch 2 region of yeast RNA polymerase II in
      transcription start site utilization and abortive initiation.
AB  - RNA polymerase II (RNAPII) is responsible for the synthesis of mRNA from
      eukaryotic protein-encoding genes. In this study, site-directed mutagenesis was
      employed to probe the function of residues within the Saccharomyces cerevisiae
      RNAPII active center in the mechanism of transcription start site utilization. We
      report here the identification of two mutations in the switch 2 region, rpb1
      K332A and rpb1-R344A, which conferred conditional growth properties and
      downstream shifts in start site utilization. Analyses of double mutant strains
      demonstrated functional interactions between these switch 2 mutations and a
      mutation in the largest subunit of transcription factor IIF (TFIIF) that confers
      upstream shifts in start site usage. Importantly, biochemical analyses
      demonstrated that purified Rpb1-R344A mutant polymerase exhibited impaired
      ability to stabilize a short RNA-DNA hybrid in the active center, an increased
      frequency of abortive transcription in runoff assays, and both a downstream shift
      and increased abortive initiation in reconstituted transcription assays. These
      results provide evidence for a role of switch 2 during start site utilization and
      indicate that RNA-DNA hybrid stability at the 3'-end of the transcript is a
      determinant in this process. We discuss these results within the context of a
      proposed model regarding the concerted roles of RNAPII, TFIIB, and TFIIF during
      mRNA 5'-end formation in S. cerevisiae.

PMID- 16081423
TI  - Differential regulation of CDP/Cux p110 by cyclin A/Cdk2 and cyclin A/Cdk1.
AB  - Previous experiments with peptide fusion proteins suggested that cyclin A/Cdk1
      and Cdk2 might exhibit similar yet distinct phosphorylation specificities. Using
      a physiological substrate, CDP/Cux, our study confirms this notion. Proteolytic
      processing of CDP/Cux by cathepsin L generates the CDP/Cux p110 isoform at the
      beginning of S phase. CDP/Cux p110 makes stable interactions with DNA during S
      phase but is inhibited in G2 following the phosphorylation of serine 1237 by
      cyclin A/Cdk1. In this study, we propose that differential phosphorylation by
      cyclin A/Cdk1 and cyclin A/Cdk2 enables CDP/Cux p110 to exert its function as a
      transcriptional regulator specifically during S phase. We found that like cyclin
      A/Cdk1, cyclin A/Cdk2 interacted efficiently with recombinant CDP/Cux proteins
      that contain the Cut homeodomain and an adjacent cyclin-binding motif (Cy). In
      contrast to cyclin A/Cdk1, however, cyclin A/Cdk2 did not efficiently
      phosphorylate CDP/Cux p110 on serine 1237 and did not inhibit its DNA binding
      activity in vitro. Accordingly, co-expression with cyclin A/Cdk2 in cells did not
      inhibit the DNA binding and transcriptional activities of CDP/Cux p110. To
      confirm that the sequence surrounding serine 1237 was responsible for the
      differential regulation by Cdk1 and Cdk2, we replaced 4 amino acids flanking the
      phosphorylation site to mimic a known Cdk2 phosphorylation site present in the
      Cdc6 protein. Both cyclin A/Cdk2 and Cdk1 efficiently phosphorylated the
      CDP/Cux(Cdc6) mutant and inhibited its DNA binding activity. Altogether our
      results help explain why the DNA binding activity of CDP/Cux p110 is maximal
      during S phase and decreases in G2 phase.

PMID- 16081424
TI  - The role of ubiquitination in Drosophila innate immunity.
AB  - Infection of Drosophila by Gram-negative bacteria triggers a signal transduction
      pathway (the IMD pathway) culminating in the expression of genes encoding
      antimicrobial peptides. A key component in this pathway is a Drosophila IkappaB
      kinase (DmIKK) complex, which stimulates the cleavage and activation of the NF
      kappaB transcription factor Relish. Activation of the DmIKK complex requires the
      MAP3K dTAK1, but the mechanism of dTAK1 activation is not understood. In human
      cells, the activation of TAK1 and IKK requires the human ubiquitin-conjugating
      enzymes Ubc13 and UEV1a. Here we demonstrate that the Drosophila homologs of
      Ubc13 and UEV1a are similarly required for the activation of dTAK1 and the DmIKK
      complex. Surprisingly, we find that the Drosophila caspase DREDD and its partner
      dFADD are required for the activation of DmIKK and JNK, in addition to their role
      in Relish cleavage. These studies reveal an evolutionarily conserved role of
      ubiquitination in IKK activation, and provide new insights into the hierarchy of
      signaling components in the Drosophila antibacterial immunity pathway.

PMID- 16081425
TI  - Glutamate cysteine ligase catalysis: dependence on ATP and modifier subunit for
      regulation of tissue glutathione levels.
AB  - Glutamate cysteine ligase (GCL), which synthesizes gamma-glutamyl-cysteine (gamma
      GC), is the rate-limiting enzyme in GSH biosynthesis. gamma-GC may be produced by
      the catalytic subunit GCLC or by the holoenzyme (GCLholo), which comprises GCLC
      and the modifier subunit GCLM. The Gclm(-/-) knock-out mouse shows tissue levels
      of GSH that are between 9 and 40% of the Gclm(+/+) wild-type mouse. In the
      present study, we used recombinant GCLC and GCLM and Gclm(-/-) mice to examine
      the role of GCLM on gamma-GC synthesis by GCLholo. GCLM decreased the Km for ATP
      by approximately 6-fold and, similar to other species, decreased the Km for
      glutamate and increased the Ki for feedback inhibition by GSH. Furthermore, GCLM
      increased by 4.4-fold the Kcat for gamma-GC synthesis; this difference in
      catalytic efficiency of GCLholo versus GCLC allowed us to derive a mathematical
      relationship for gamma-GC production and to determine the relative levels of
      GCLholo and GCLC; in homogenates of brain, liver, and lung, the ratio of GCLC to
      GCLholo was 7.0, 2.0, and 3.5, respectively. In kidney, however, the relationship
      between GCLC and GCLholo was complicated. Kidney contains GCLholo, free GCLC, and
      free GCLM, and free GCLC in kidney cannot interact with GCLM. Taken together, we
      conclude that, in most tissues, GCLM is limiting, suggesting that an increase in
      GCLM alone would increase gamma-GC synthesis. On the other hand, our results from
      kidney suggest that gamma-GC synthesis may be controlled post-translationally.

PMID- 16081426
TI  - Platelet-derived growth factor and reactive oxygen species (ROS) regulate Ras
      protein levels in primary human fibroblasts via ERK1/2. Amplification of ROS and
      Ras in systemic sclerosis fibroblasts.
AB  - The levels of Ras proteins in human primary fibroblasts are regulated by PDGF
      (platelet-derived growth factor). PDGF induced post-transcriptionally Ha-Ras by
      stimulating reactive oxygen species (ROS) and ERK1/2. Activation of ERK1/2 and
      high ROS levels stabilize Ha-Ras protein, by inhibiting proteasomal degradation.
      We found a remarkable example in vivo of amplification of this circuitry in
      fibroblasts derived from systemic sclerosis (scleroderma) lesions, producing vast
      excess of ROS and undergoing rapid senescence. High ROS, Ha-Ras, and active
      ERK1/2 stimulated collagen synthesis, DNA damage, and accelerated senescence.
      Conversely ROS or Ras inhibition interrupted the signaling cascade and restored
      the normal phenotype. We conclude that in primary fibroblasts stabilization of
      Ras protein by ROS and ERK1/2 amplifies the response of the cells to growth
      factors and in systemic sclerosis represents a critical factor in the onset and
      progression of the disease.

PMID- 16081428
TI  - Delayed prescribing of antibiotics for upper respiratory tract infection.

PMID- 16081427
TI  - Skin biopsy rates and incidence of melanoma: population based ecological study.
AB  - OBJECTIVES: To describe changes in skin biopsy rates and to determine their
      relation with changes in the incidence of melanoma. DESIGN: Population based
      ecological study. SETTING: Nine geographical areas of the United States.
      PARTICIPANTS: Participants of the Surveillance Epidemiology and End Results
      (SEER) programme aged 65 and older. MAIN OUTCOME MEASURES: For the period 1986 to
      2001, annual skin biopsy rates for each surveillance area from Medicare claims
      and incidence rates for melanoma for the same population. RESULTS: Between 1986
      and 2001 the average biopsy rate across the nine participating areas increased
      2.5-fold among people aged 65 and older (2847 to 7222 per 100,000 population).
      Over the same period the average incidence of melanoma increased 2.4-fold (45 to
      108 per 100,000 population). Assuming that the occurrence of true disease was
      constant, the extra number of melanoma cases that were diagnosed after carrying
      out 1000 additional biopsies was 12.6 (95% confidence interval 11.2 to 14.0).
      After controlling for a potential increase in the true occurrence of disease,
      1000 additional biopsies were still associated with 6.9 (3.1 to 10.8) extra
      melanoma cases diagnosed. Stage specific analyses suggested that 1000 biopsies
      were associated with 4.4 (2.1 to 6.8) extra cases of in situ melanoma diagnosed
      and 2.3 (0.0 to 4.6) extra cases of local melanoma, but not with the incidence of
      advanced melanoma. Mortality from melanoma changed little during the period.
      CONCLUSION: The incidence of melanoma is associated with biopsy rates. That the
      extra cases diagnosed were confined to early stage cancer while mortality
      remained stable suggests overdiagnosis-the increased incidence being largely the
      result of increased diagnostic scrutiny and not an increase in the incidence of
      disease.

PMID- 16081429
TI  - Vitamin and mineral supplements for preventing infections in older people.

PMID- 16081430
TI  - Roles and responsibilities of medical expert witnesses.

PMID- 16081431
TI  - Mumbai braces itself for leptospirosis and waterborne infections.

PMID- 16081432
TI  - US Senate leader gives support to expanded stem cell research.

PMID- 16081433
TI  - Fertility agency is to investigate single embryo transfer.

PMID- 16081434
TI  - Resistance to antiviral drugs is climbing.

PMID- 16081435
TI  - Court rules in favour of GMC's guidance on withholding treatment.

PMID- 16081437
TI  - Abortions reach highest ever number in England and Wales.

PMID- 16081438
TI  - Trade agreement may restrict supply of essential drugs in Central America,
      experts say.

PMID- 16081443
TI  - The man with the IT plan.

PMID- 16081444
TI  - Cholinesterase inhibitors for patients with Alzheimer's disease: systematic
      review of randomised clinical trials.
AB  - OBJECTIVES: Pharmacological treatment of Alzheimer's disease focuses on
      correcting the cholinergic deficiency in the central nervous system with
      cholinesterase inhibitors. Three cholinesterase inhibitors are currently
      recommended: donepezil, rivastigmine, and galantamine. This review assessed the
      scientific evidence for the recommendation of these agents. DATA SOURCES: The
      terms "donepezil", "rivastigmine", and "galantamine", limited by "randomized
      controlled-trials" were searched in Medline (1989-November 2004), Embase (1989
      November 2004), and the Cochrane Database of Systematic Reviews without
      restriction for language. STUDY SELECTION: All published, double blind,
      randomised controlled trials examining efficacy on the basis of clinical
      outcomes, in which treatment with donepezil, rivastigmine, or galantamine was
      compared with placebo in patients with Alzheimer's disease, were included. Each
      study was assessed independently, following a predefined checklist of criteria of
      methodological quality. RESULTS: 22 trials met the inclusion criteria. Follow-up
      ranged from six weeks to three years. 12 of 14 studies measuring the cognitive
      outcome by means of the 70 point Alzheimer's disease assessment scale--cognitive
      subscale showed differences ranging from 1.5 points to 3.9 points in favour of
      the respective cholinesterase inhibitors. Benefits were also reported from all 12
      trials that used the clinician's interview based impression of change scale with
      input from caregivers. Methodological assessment of all studies found
      considerable flaws--for example, multiple testing without correction for
      multiplicity or exclusion of patients after randomisation. CONCLUSION: Because of
      flawed methods and small clinical benefits, the scientific basis for
      recommendations of cholinesterase inhibitors for the treatment of Alzheimer's
      disease is questionable.

PMID- 16081446
TI  - Anaphylaxis.

PMID- 16081445
TI  - Effect of multivitamin and multimineral supplements on morbidity from infections
      in older people (MAVIS trial): pragmatic, randomised, double blind, placebo
      controlled trial.
AB  - OBJECTIVE: To examine whether supplementation with multivitamins and
      multiminerals influences self reported days of infection, use of health services,
      and quality of life in people aged 65 or over. DESIGN: Randomised, placebo
      controlled trial, with blinding of participants, outcome assessors, and
      investigators. SETTING: Communities associated with six general practices in
      Grampian, Scotland. PARTICIPANTS: 910 men and women aged 65 or over who did not
      take vitamins or minerals. INTERVENTIONS: Daily multivitamin and multimineral
      supplementation or placebo for one year. MAIN OUTCOME MEASURES: Primary outcomes
      were contacts with primary care for infections, self reported days of infection,
      and quality of life. Secondary outcomes included antibiotic prescriptions,
      hospital admissions, adverse events, and compliance. RESULTS: Supplementation did
      not significantly affect contacts with primary care and days of infection per
      person (incidence rate ratio 0.96, 95% confidence interval 0.78 to 1.19 and 1.07,
      0.90 to 1.27). Quality of life was not affected by supplementation. No
      statistically significant findings were found for secondary outcomes or
      subgroups. CONCLUSION: Routine multivitamin and multimineral supplementation of
      older people living at home does not affect self reported infection related
      morbidity. TRIAL REGISTRATION: ISRCTN: 66376460.

PMID- 16081447
TI  - Challenges to implementing the national programme for information technology
      (NPfIT): a qualitative study.
AB  - OBJECTIVES: To describe the context for implementing the national programme for
      information technology (NPfIT) in England, actual and perceived barriers, and
      opportunities to facilitate implementation. DESIGN: Case studies and in depth
      interviews, with themes identified using a framework developed from grounded
      theory. SETTING: Four acute NHS trusts in England. PARTICIPANTS: Senior trust
      managers and clinicians, including chief executives, directors of information
      technology, medical directors, and directors of nursing. RESULTS: The trusts
      varied in their circumstances, which may affect their ability to implement the
      NPfIT. The process of implementation has been suboptimal, leading to reports of
      low morale by the NHS staff responsible for implementation. The overall timetable
      is unrealistic, and trusts are uncertain about their implementation schedules.
      Short term benefits alone are unlikely to persuade NHS staff to adopt the
      national programme enthusiastically, and some may experience a loss of electronic
      functionality in the short term. CONCLUSIONS: The sociocultural challenges to
      implementing the NPfIT are as daunting as the technical and logistical ones.
      Senior NHS staff feel these have been neglected. We recommend that national
      programme managers prioritise strategies to improve communication with, and to
      gain the cooperation of, front line staff.

PMID- 16081448
TI  - Beware of multiple names in database linkage research: prevalence of aliases in
      female prison population.

PMID- 16081449
TI  - Management of severe malaria in children: proposed guidelines for the United
      Kingdom.

PMID- 16081450
TI  - Approaches to conflict resolution.

PMID- 16081452
TI  - Model of outcomes of screening mammography: Information needs to support informed
      choices.

PMID- 16081451
TI  - Hormone replacement therapy and breast cancer: estimate of risk.

PMID- 16081453
TI  - Model of outcomes of screening mammography: spontaneous regression of breast
      cancer may not be uncommon.

PMID- 16081454
TI  - Radiation from CT and perfusion scanning in pregnancy.

PMID- 16081455
TI  - Methods of hysterectomy: should women have a say?

PMID- 16081456
TI  - Model of outcomes of screening mammography: women's decisions about screening
      depend on many factors.

PMID- 16081457
TI  - Where next with revalidation? Make CME and CPD compulsory with support of audit
      and mentoring.

PMID- 16081458
TI  - Where next with revalidation? Smart money is on using new communications
      technology effectively.

PMID- 16081459
TI  - Changes in atopy over 25 years: atopy now affects wider age range.

PMID- 16081460
TI  - Changes in atopy over 25 years: allergy epidemic has spread to old age.

PMID- 16081461
TI  - Future of singlehanded general practices: the NHS has room for variety.

PMID- 16081462
TI  - Future of singlehanded general practices: all doctors must show that they work to
      acceptable standards.

PMID- 16081463
TI  - Where next with revalidation? Political will does not exist for radical reform.

PMID- 16081464
TI  - Dermatitis in hairdressers as a problem in chemical control.

PMID- 16081465
TI  - Occupational dermal exposure to permanent hair dyes among hairdressers.
AB  - Skin exposure to permanent hair dye compounds was assessed in 33 hairdressers
      using a previously evaluated hand rinse method. Hand rinse samples were collected
      from each hand before the start of hair dyeing, after application of the dye and
      after cutting the newly-dyed hair. Sixteen of the hairdressers did not use gloves
      during dye application, and none used gloves while cutting the dyed hair. The
      samples were analysed for pertinent aromatic amines and resorcinol (RES) using an
      HPLC method. 10 of 54 hair dye mixtures contained 1,4-phenylenediamine (PPD), 40
      toluene-2,5-diaminesulphate (TDS), and 44 RES. After application of the hair dye,
      PPD was found in samples from 4 hairdressers, TDS in 12 and RES in 21. PPD was
      found in samples from 3 of the 17 hairdressers that used gloves during
      application of the hair dye, TDS in 5 and RES in 11. In the group that did not
      use gloves during the application of hair dye (n = 16) PPD was found in samples
      from 1 hairdresser, TDS in 7 and RES in 11. After cutting the dyed hair, PPD was
      found in samples from 5 hairdressers, TDS in 14 and RES in 20. Analysis of
      samples of newly-dyed hair cuttings revealed the presence of aromatic amines
      and/or RES in 11/12 samples. Our conclusion is that hairdressers' skin is exposed
      to allergenic compounds during hair dyeing. Exposure occurs from dye application,
      from cutting newly-dyed hair and from background exposure. The exposure loadings
      are in the level, where there is a risk of sensitization and/or elicitation of
      contact allergy (i.e. for PPD 22-939 nmol per hand). The glove use observed in
      this study was often improper, and was insufficient to prevent exposure. To
      reduce exposure, improved skin protection and work routines are important.

PMID- 16081466
TI  - Functional promoter SNPs in cell cycle checkpoint genes.
AB  - A substantial number of genes mutated in human cancers encode components of the
      cell cycle processes. As the G1/S transition in the cell cycle is a finely
      regulated biological process, we hypothesized that sequence variations in the
      promoter region of the related genes might indeed lead to abnormal expression,
      thus predisposing the individuals carrying these genetic variants to cancer. In
      this report, we screened the promoter regions of 16 cell cycle checkpoint genes
      for DNA variants and assessed the functional impact of these promoter region
      single nucleotide polymorphisms (pSNPs) by combining in silico analysis and in
      vitro functional assays. We identified 127 pSNPs including 90 with predicted
      impact on putative binding sites of known transcription factors. Eleven pSNPs
      were selected for electrophoresis mobility shift assays because of their
      association with predicted gains of binding sites, and nine pSNPs showed
      differential allelic shifts in at least one cell line tested. Following the
      subcloning of the promoter regions into a gene reporter system, we found that at
      least four promoter haplotypes associated with CCND1, E2F1, HDAC1 and RB1
      significantly influenced transcriptional activity in an allele-specific manner.
      Although the biological significance of these observations still remains to be
      demonstrated, the expected variability of expression levels in key cell cycle
      components might influence individual's risk of cancer.

PMID- 16081467
TI  - The establishment of a predictive mutational model of the forkhead domain through
      the analyses of FOXC2 missense mutations identified in patients with hereditary
      lymphedema with distichiasis.
AB  - The FOX family of transcription factor genes is an evolutionary conserved, yet
      functionally diverse class of transcription factors that are important for
      regulation of energy homeostasis, development and oncogenesis. The proteins
      encoded by FOX genes are characterized by a conserved DNA-binding domain known as
      the forkhead domain (FHD). To date, disease-causing mutations have been
      identified in eight human FOX genes. Many of these mutations result in single
      amino acid substitutions in the FHD. We analyzed the molecular consequences of
      two disease-causing missense mutations (R121H and S125L) occurring in the FHD of
      the FOXC2 gene that were identified in patients with hereditary lymphedema with
      distichiasis (LD) to test the predictive capacity of a FHD structure/function
      model. On the basis of the FOXC2 solution structure, both FOXC2 missense
      mutations are located on the DNA-recognition helix of the FHD. A mutation model
      based on the parologous FOXC1 protein predicts that these FOXC2 missense
      mutations will impair the DNA-binding and transcriptional activation ability of
      the FOXC2 protein. When these mutations were analyzed biochemically, we found
      that both mutations did indeed reduce the DNA binding and transcriptional
      capacity. In addition, the R121H mutation affected nuclear localization of FOXC2.
      Together, these data indicate that these FOXC2 missense mutations are functional
      nulls and that FOXC2 haploinsufficiency underlies hereditary LD and validates the
      predictive ability of the FOXC1-based FHD mutational model.

PMID- 16081468
TI  - Do angiotensin II receptor blockers increase the risk of myocardial infarction?
AB  - AIMS: The uncertainty surrounding safety of angiotensin receptor blockers (ARBs)
      increased after publication of experimental and clinical studies which suggested
      an excess risk of myocardial infarction (MI) in people treated with ARBs. METHODS
      AND RESULTS: We performed a meta-analysis of randomised clinical trials, which
      compared ARBs with either a placebo or active drugs different from ARBs. Overall,
      ARBs were not associated with an excess risk of MI [odds ratio (OR): 1.03 in a
      random-effect model and 1.02 in a fixed-effect model]. In pre-specified subgroup
      analyses, incidence of MI did not differ between ARBs and either placebo (OR:
      0.96; 95% CI: 0.84-1.10) or angiotensin-converting enzyme (ACE)-Inhibitors (OR:
      0.99; 95% CI: 0.91-1.07). Incidence of MI was slightly higher with ARBs than with
      drug classes different from ACE-Inhibitors (OR: 1.16; P=0.06 in a random-effect
      model and 0.017 in a fixed-effect model). Cardiovascular mortality did not differ
      between ARBs and drugs different from ARBs (OR: 1.00 in a random-effect model and
      0.99 in a fixed-effect model) and it was slightly lesser with ARBs than with
      placebo (OR: 0.91; 95% CI: 0.83-0.99; P=0.042) in a pre-specified subgroup
      analysis. CONCLUSION: Our findings do not support the hypothesis that ARBs
      increase the risk of MI.

PMID- 16081469
TI  - The effect of micronutrient supplementation on quality-of-life and left
      ventricular function in elderly patients with chronic heart failure.
AB  - AIMS: Chronic heart failure (CHF) is a common and leading cause of death in
      industrialized countries. The potential benefits of micronutrient supplementation
      in CHF are extensive. Therefore, we examined the influence of long-term multiple
      micronutrient supplementation on left ventricular (LV) function, levels of pro
      inflammatory cytokines, and quality-of-life (QoL) in elderly patients with CHF.
      METHODS AND RESULTS: Thirty CHF patients [age 75.4 (0.7), mean (SEM), LV ejection
      fraction (LVEF) < or =35%] were randomized to receive capsules containing a
      combination of high-dose micronutrients (calcium, magnesium, zinc, copper,
      selenium, vitamin A, thiamine, riboflavin, vitamin B(6), folate, vitamin B(12),
      vitamin C, vitamin E, vitamin D, and Coenzyme Q10) or placebo for 9 months in a
      double-blind fashion. All subjects were on stable optimal medical therapy for at
      least 3 months before enrolment. At randomization and at study end, tumour
      necrosis factor-alpha and its soluble receptors TNFR-1 and TNFR-2 were measured
      and six-minute walk test and QoL were assessed. Cardiac magnetic resonance
      scanning was performed to evaluate cardiac dimensions and LVEF. Two patients died
      during follow-up. The remaining patients (14 randomized to placebo and 14 to
      micronutrients) were well matched for LV function, symptoms, and exercise
      capacity. At the end of the follow-up period, LV volumes were reduced in the
      intervention group with no change in the placebo group [-13.1 (17.1)% vs. +3.8
      (10.0)%; P<0.05]. LVEF increased by 5.3+/-1.4% in the intervention group and was
      unchanged in the placebo group (P<0.05). Patients taking micronutrients also had
      a significant improvement in QoL score between enrolment and study end [+9.5
      (1.6)%; P<0.05], whereas those taking placebo had a slight deterioration [-1.1
      (0.8)%; P=0.12]. Six-minute walk test and inflammatory cytokine levels remained
      unchanged in both groups. CONCLUSION: Long-term multiple micronutrient
      supplementation can improve LV volumes and LVEF and QoL scores in elderly
      patients with heart failure due to LV systolic dysfunction.

PMID- 16081470
TI  - PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence
      for presymptomatic compensation.
AB  - Parkinson's disease may arise from multiple aetiologies, including genetic
      mutations that are for the most part uncommon. We describe here the positron
      emission tomography (PET) findings in clinically affected and asymptomatic, high
      risk members of two autosomal dominantly inherited Parkinson's disease kindreds
      with recently described mutations at the PARK8 locus, in a novel gene encoding a
      leucine-rich repeat kinase (LRRK2). Affected family members have L-dopa
      responsive parkinsonism with loss of dopaminergic nigral neurons and pleomorphic
      subcellular pathology. Fifteen family members underwent PET using: 18F-6-fluoro-L
      dopa (18F-dopa) to assess dopamine (DA) synthesis and storage, 11C-(+/-)
      dihydrotetrabenazine (11C-DTBZ) for the vesicular monoamine transporter, and 11C
      d-threo-methylphenidate (11C-MP) for the membrane dopamine transporter (DAT).
      Measurements were compared with normal (n = 33) and sporadic Parkinson's disease
      (sPD) (n = 67) control groups. Four clinically affected members had findings
      similar to sPD, with impaired presynaptic DA function affecting the putamen more
      than the caudate. In two affected members, D2 dopamine receptor binding was
      intact. Two asymptomatic mutation carriers had abnormal DAT binding with another
      two developing such abnormalities over 4 years of follow-up. In these
      individuals, 18F-dopa uptake remained normal, although two of them also displayed
      abnormal 11C-DTBZ binding. Our study demonstrates that the in vivo neurochemical
      phenotype of LRRK2 mutations is indistinguishable from that of sPD, despite the
      pathological heterogeneity of the condition. Furthermore, we suggest that
      compensatory changes including downregulation of the DAT and upregulation of
      decarboxylase activity may delay the onset of parkinsonian symptoms.

PMID- 16081471
TI  - 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone [MX] shows initiating and
      promoting activities in a two-stage BALB/c 3T3 cell transformation assay.
AB  - A transformation assay using BALB/c 3T3 cells was conducted on 3-chloro-4
      (dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to assess initiation and promotion
      activities of MX carcinogenesis. Statistically significant positive responses
      were obtained compared with the corresponding solvent controls in both the
      initiation assay post-treated with 12-O-tetradecanoylphorbol 13-acetate (TPA) and
      the promotion assay pretreated with 3-methylcholanthrene (MCA). Both TPA and MX
      inhibited metabolic cooperation in an assay using co-culture of V79 6-thioguanine
      (6-TG) sensitive and insensitive cells. However, cells isolated from transformed
      foci in the initiation assay did not induce any nodules after inoculation to
      BALB/c mice, the strain of mouse from which the transformation assay cells were
      derived. Although the study was carried out for 2-3 weeks, this might have been
      too short to develop nodules under the conditions of this experiment. This in
      vitro cell transformation study with MX adds supportive information to studies
      showing MX carcinogenicity and tumour promoter activity, and adds mechanistic
      understanding of the action of MX.

PMID- 16081472
TI  - Interferon-alpha as maintenance therapy in patients with multiple myeloma.

PMID- 16081473
TI  - Comparative analysis of algorithms for identifying amplifications and deletions
      in array CGH data.
AB  - MOTIVATION: Array Comparative Genomic Hybridization (CGH) can reveal chromosomal
      aberrations in the genomic DNA. These amplifications and deletions at the DNA
      level are important in the pathogenesis of cancer and other diseases. While a
      large number of approaches have been proposed for analyzing the large array CGH
      datasets, the relative merits of these methods in practice are not clear.
      RESULTS: We compare 11 different algorithms for analyzing array CGH data. These
      include both segment detection methods and smoothing methods, based on diverse
      techniques such as mixture models, Hidden Markov Models, maximum likelihood,
      regression, wavelets and genetic algorithms. We compute the Receiver Operating
      Characteristic (ROC) curves using simulated data to quantify sensitivity and
      specificity for various levels of signal-to-noise ratio and different sizes of
      abnormalities. We also characterize their performance on chromosomal regions of
      interest in a real dataset obtained from patients with Glioblastoma Multiforme.
      While comparisons of this type are difficult due to possibly sub-optimal choice
      of parameters in the methods, they nevertheless reveal general characteristics
      that are helpful to the biological investigator.

PMID- 16081474
TI  - Blast2GO: a universal tool for annotation, visualization and analysis in
      functional genomics research.
AB  - SUMMARY: We present here Blast2GO (B2G), a research tool designed with the main
      purpose of enabling Gene Ontology (GO) based data mining on sequence data for
      which no GO annotation is yet available. B2G joints in one application GO
      annotation based on similarity searches with statistical analysis and highlighted
      visualization on directed acyclic graphs. This tool offers a suitable platform
      for functional genomics research in non-model species. B2G is an intuitive and
      interactive desktop application that allows monitoring and comprehension of the
      whole annotation and analysis process. AVAILABILITY: Blast2GO is freely available
      via Java Web Start at http://www.blast2go.de. SUPPLEMENTARY MATERIAL:
      http://www.blast2go.de -> Evaluation.

PMID- 16081475
TI  - Bifurcation discovery tool.
AB  - MOTIVATION: Biochemical networks often yield interesting behavior such as
      switching, oscillation and chaotic dynamics. This article describes a tool that
      is capable of searching for bifurcation points in arbitrary ODE-based reaction
      networks by directing the user to regions in the parameter space, where such
      interesting dynamical behavior can be observed. RESULTS: We have implemented a
      genetic algorithm that searches for Hopf bifurcations, turning points and
      bistable switches. The software is implemented as a Systems Biology Workbench
      (SBW) enabled module and accepts the standard SBML model format. The interface
      permits a user to choose the parameters to be searched, admissible parameter
      ranges, and the nature of the bifurcation to be sought. The tool will return the
      parameter values for the model for which the particular behavior is observed.
      AVAILABILITY: The software, tutorial manual and test models are available for
      download at the following website: http:/www.sys-bio.org/ under the bifurcation
      link. The software is an open source and licensed under BSD.

PMID- 16081476
TI  - Analysis of dose-response effects on gene expression data with comparison of two
      microarray platforms.
AB  - MOTIVATION: The problems of analyzing dose effects on gene expression are gaining
      attention in biomedical research. A specific challenge is to detect genes with
      expression levels that change according to dose levels in a non-random manner,
      but nonetheless may be considered as potential biomarkers. METHOD: We are among
      the first to formally apply a tool that uses an isotonic (monotonic) regression
      approach to this area of study. We introduce a test statistic to select genes
      with significant dose-response expression in a monotonic fashion based on a
      permutation procedure. We then compare the results with those achieved from the
      application of a likelihood ratio-based test. RESULTS: We apply the isotonic
      regression approach to a study of gene expression in the RKO colon carcinoma cell
      line in response to varying dosage levels of the chemotherapeutic agent 5
      fluorouracil. A feature of both Affymetrix and printed 75mer oligomer cDNA arrays
      produced from the same samples provides an opportunity to compare the two
      microarray platforms. AVAILABILITY: Statistical software S-plus Code to implement
      the method is available from the authors. CONTACT: kcoombes@mdanderson.org

PMID- 16081477
TI  - Influence of recombinant human erythropoietin treatment on pulmonary O2 uptake
      kinetics during exercise in humans.
AB  - We hypothesized that 4 weeks of recombinant human erythropoietin (RhEPO)
      treatment would result in a significant increase in haemoglobin concentration
      ([Hb]) and arterial blood O(2)-carrying capacity and that this would (1) increase
      peak pulmonary oxygen uptake during ramp incremental exercise, and (2) speed
      kinetics during 'severe'-, but not 'moderate'- or 'heavy'-intensity, step
      exercise. Fifteen subjects (mean +/- s.d. age 25 +/- 4 years) were randomly
      assigned to either an experimental group which received a weekly subcutaneous
      injection of RhEPO (150 IU kg(-1); n = 8), or a control group (CON) which
      received a weekly subcutaneous injection of sterile saline (10 ml; n = 7) as a
      placebo, for four weeks. The subjects and the principal researchers were both
      blind with respect to the group assignment. Before and after the intervention
      period, all subjects completed a ramp test for determination of the gas exchange
      threshold (GET) and , and a number of identical 'step' transitions from
      'unloaded' cycling to work rates requiring 80% GET (moderate), 70% of the
      difference between the GET and (heavy), and 105% (severe) as determined from the
      initial ramp test. Pulmonary gas exchange was measured breath-by-breath. There
      were no significant differences between the RhEPO and CON groups for any of the
      measurements of interest ([Hb], kinetics) before the intervention. Four weeks of
      RhEPO treatment resulted in a 7% increase both in [Hb] (from 15.8 +/- 1.0 to 16.9
      +/- 0.7 g dl(-1); P < 0.01) and (from 47.5 +/- 4.2 to 50.8 +/- 10.7 ml kg(
      1).min(-1); P < 0.05), with no significant change in CON. RhEPO had no
      significant effect on kinetics for moderate (Phase II time constant, from 28 +/-
      8 to 28 +/- 7 s), heavy (from 37 +/- 12 to 35 +/- 11 s), or severe (from 33 +/-
      15 to 35 +/- 15 s) step exercise. Our results indicate that enhancing blood O(2)
      carrying capacity and thus the potential for muscle O(2) delivery with RhEPO
      treatment enhanced the peak but did not influence kinetics, suggesting that the
      latter is principally regulated by intracellular (metabolic) factors, even during
      exercise where the requirement is greater than the , at least in young subjects
      performing upright cycle exercise.

PMID- 16081478
TI  - Metachronal propagation of motoneurone burst activation in isolated spinal cord
      of newborn rat.
AB  - Adequate locomotor and postural activity in mammals results from the coordinated
      activation of assemblies of spinal cord networks. In order to assess the global
      functioning of spinal circuitry, multisite recordings were made from an isolated
      spinal cord preparation of the newborn rat. Motor activity, elicited in a
      disinhibited network by bath-applying strychnine (glycinergic blocker) and
      bicuculline (GABAergic blocker), consisted of slow spontaneous bursting. Under
      these conditions, the recorded bursts were coordinated in 1: 1 relationships at
      all segmental levels. For each cycle, a leading segment initiated the activity
      that then propagated in a metachronal way through adjacent segments along the
      length of spinal cord. There was both regional non-linearity and directional
      asymmetry in this burst propagation: motor bursts propagated most rapidly in the
      thoracic spinal cord and the rostro-caudal wave travelled faster than the caudo
      rostral one. Propagation involved both long projecting fibres and local
      intersegmental connections. These results suggest that the mammalian spinal cord
      contains propriospinal pathways subserving a metachronal transmission of motor
      information and that normally it may be involved in coordinating various parts of
      the body. The simple model developed here could be useful in unravelling more
      general mechanisms of neuronal circuit coupling.

PMID- 16081479
TI  - Disruption of CFTR chloride channel alters mechanical properties and cAMP
      dependent Cl- transport of mouse aortic smooth muscle cells.
AB  - Chloride (Cl(-)) channels expressed in vascular smooth muscle cells (VSMC) are
      important to control membrane potential equilibrium, intracellular pH, cell
      volume maintenance, contraction, relaxation and proliferation. The present study
      was designed to compare the expression, regulation and function of CFTR Cl(-)
      channels in aortic VSMC from Cftr(+/+) and Cftr(-)(/)(-) mice. Using an iodide
      efflux assay we demonstrated stimulation of CFTR by VIP, isoproterenol, cAMP
      agonists and other pharmacological activators in cultured VSMC from Cftr(+/+). On
      the contrary, in cultured VSMC from Cftr(-)(/)(-) mice these agonists have no
      effect, showing that CFTR is the dominant Cl(-) channel involved in the response
      to cAMP mediators. Angiotensin II and the calcium ionophore A23187 stimulated
      Ca(2)(+)-dependent Cl(-) channels in VSMCs from both genotypes. CFTR was
      activated in myocytes maintained in medium containing either high potassium or 5
      hydroxytryptamine (5-HT) and was inhibited by CFTR(inh)-172, glibenclamide and
      diphenylamine-2,2'-dicarboxylic acid (DPC). We also examined the mechanical
      properties of aortas. Arteries with or without endothelium from Cftr(-/-) mice
      became significantly more constricted (approximately 2-fold) than that of
      Cftr(+/+) mice in response to vasoactive agents. Moreover, in precontracted
      arteries of Cftr(+/+) mice, VIP and CFTR activators induced vasorelaxation that
      was altered in Cftr(-/-) mice. Our findings suggest a novel mechanism for
      regulation of the vascular tone by cAMP-dependent CFTR chloride channels in VSMC.
      To our knowledge this study is the first to report the phenotypic consequences of
      the loss of a Cl(-) channel on vascular reactivity.

PMID- 16081480
TI  - Governor recalled! Now what?

PMID- 16081481
TI  - Carbachol induces burst firing of dopamine cells in the ventral tegmental area by
      promoting calcium entry through L-type channels in the rat.
AB  - Enhanced activity of the central dopamine system has been implicated in many
      psychiatric disorders including schizophrenia and addiction. Besides terminal
      mechanisms that boost dopamine levels at the synapse, the cell body of dopamine
      cells enhances terminal dopamine concentration through encoding action potentials
      in bursts. This paper presents evidence that burst firing of dopamine cells in
      the ventral tegmental area was under cholinergic control using nystatin
      perforated patch clamp recording from slice preparations. The non-selective
      cholinergic agonist carbachol excited the majority of recorded neurones, an
      action that was not affected by blocking glutamate and GABA ionotropic receptors.
      Twenty per cent of dopamine cells responded to carbachol with robust bursting, an
      effect mediated by both muscarinic and nicotinic cholinoceptors postsynaptically.
      Burst firing induced as such was completely dependent on calcium entry as it
      could be blocked by cadmium and more specifically the L-type blocker nifedipine.
      In the presence of the sodium channel blocker tetrodotoxin, carbachol induced
      membrane potential oscillation that had similar kinetics and frequency as burst
      firing cycles and could also be blocked by cadmium and nifedipine. Direct
      activation of the L-type channel with Bay K8644 induced strong bursting which
      could be blocked by nifedipine but not by depleting internal calcium stores.
      These results indicate that carbachol increases calcium entry into the
      postsynaptic cell through L-type channels to generate calcium-dependent membrane
      potential oscillation and burst firing. This could establish the L-type channel
      as a target for modulating the function of the central dopamine system in disease
      conditions.

PMID- 16081482
TI  - Median preoptic neurones projecting to the hypothalamic paraventricular nucleus
      respond to osmotic, circulating Ang II and baroreceptor input in the rat.
AB  - The present study sought to determine whether individual neurones of the median
      preoptic nucleus (MnPO) with axonal projections to the hypothalamic
      paraventricular nucleus (MnPO-PVN) respond to osmotic, circulating angiotensin II
      (Ang II), and baroreceptor stimulation. Hypertonic NaCl (0.75 or 1.5 osmol l(-1))
      or Ang II (150 ng) was injected into the internal carotid artery (ICA).
      Baroreceptor stimulation was performed by i.v. injection of phenylephrine or
      sodium nitroprusside to increase or decrease arterial blood pressure,
      respectively. Of 65 MnPO neurones, 50 units were antidromically activated from
      the PVN with an average onset latency of 11.3 +/- 0.7 ms. Only 9.5% of MnPO-PVN
      neurones were antidromically activated from the PVN bilaterally. Type I MnPO-PVN
      neurones (n = 14) responded to osmotic but not Ang II stimulation. In 79% (11/14)
      of these type I neurones, the response was an increase in cell discharge. Type II
      MnPO-PVN neurones (n = 7) displayed a significant increase in cell discharge in
      response to ICA injection of Ang II but not hypertonic NaCl. Type III MnPO-PVN
      neurones (n = 16) responded to both ICA injection of hypertonic NaCl and Ang II.
      In 88% (14/16) of type III neurones, osmotic and Ang II stimulation each
      increased cell discharge. Type IV MnPO-PVN neurones (n = 13) displayed no change
      in cell discharge in response to ICA injection of hypertonic NaCl or Ang II.
      Baroreceptor stimulation altered the discharge in subpopulations of type I, II
      and III MnPO-PVN neurones (43-63% depending on neuronal type). Only one MnPO-PVN
      neurone responded solely to baroreceptor stimulation (type IV). In addition, a
      subset of type I, II and III neurones displayed a significant correlation with
      sympathetic nerve activity and/or the cardiac cycle. These findings suggest that
      a significant population of MnPO-PVN neurones respond to osmotic and circulating
      Ang II stimulation and thereby represents a neural substrate through which
      neurohumoral inputs are integrated within the forebrain lamina terminalis.

PMID- 16081483
TI  - Anandamide elicits an acute release of nitric oxide through endothelial TRPV1
      receptor activation in the rat arterial mesenteric bed.
AB  - In the isolated rat mesenteric bed, the 1 min perfusion with 100 nm anandamide, a
      concentration that did not evoke vasorelaxation, elicited an acute release of
      165.1 +/- 9.2 pmol nitric oxide (NO) that was paralleled by a 2-fold increase in
      cGMP tissue levels. The rise in NO released was mimicked by either (R)-(+)
      methanandamide or the vanilloid receptor agonists resiniferatoxin and (E)
      capsaicin but not by its inactive cis-isomer (Z)-capsaicin. The NO release
      elicited by either anandamide or capsaicin was reduced by the TRPV1 receptor
      antagonists 5'-iodoresiniferatoxin, SB 366791 and capsazepine as well as by the
      cannabinoid CB(1) receptor antagonists SR 141716A or AM251. The outflow of NO
      elicited by anandamide and capsaicin was also reduced by endothelium removal or
      NO synthase inhibition, suggesting the specific participation of endothelial
      TRPV1 receptors, rather than the novel endothelial TRPV4 receptors. Consistently,
      RT-PCR showed the expression of the mRNA coding for the rat TRPV1 receptor in the
      endothelial cell layer, in addition to its expression in sensory nerves. The
      participation of sensory nerves on the release of NO was precluded on the basis
      that neonatal denervation of the myenteric plexus sensory nerves did not modify
      the pattern of NO release induced by anandamide and capsaicin. We propose that
      low concentrations of anandamide, devoid of vasorelaxing effects, elicit an acute
      release of NO mediated predominantly by the activation of endothelial TRPV1
      receptors whose physiological significance remains elusive.

PMID- 16081484
TI  - Nitric oxide blunts the endothelin-mediated pulmonary vasoconstriction in
      exercising swine.
AB  - We have previously shown that vasodilators and vasoconstrictors that are produced
      by the vascular endothelium, including nitric oxide (NO), prostanoids and
      endothelin (ET), contribute to the regulation of systemic and pulmonary vascular
      tone in swine, in particular during treadmill exercise. Since NO and prostanoids
      can modulate the release of ET, and vice versa, we investigated the integrated
      endothelial control of pulmonary vascular resistance in exercising swine.
      Specifically, we tested the hypothesis that increased NO and prostanoid
      production during exercise limits the vasoconstrictor influence of ET, so that
      loss of these vasodilators results in exaggerated ET-mediated vasoconstriction
      during exercise. Fifteen instrumented swine were exercised on a treadmill at 0-5
      km h(-1) before and during ET(A)/ET(B) receptor blockade (tezosentan, 3 mg kg(-1)
      I.V.) in the presence and absence of inhibition of NO synthase (N(omega)-nitro-L
      arginine, 20 mg kg(-1) I.V.) and/or cyclo-oxygenase (indometacin, 10 mg kg(-1)
      I.V.). In the systemic circulation, ET receptor blockade decreased vascular
      resistance at rest, which waned with increasing exercise intensity. Prior
      inhibition of either NO or prostanoid production augmented the vasodilator effect
      of ET receptor blockade, and these effects were additive. In contrast, in the
      pulmonary bed, ET receptor blockade had no effect under resting conditions, but
      decreased pulmonary vascular resistance during exercise. Prior inhibition of NO
      synthase enhanced the pulmonary vasodilator effect of ET receptor blockade,
      particularly during exercise, whereas inhibition of prostanoids had no effect,
      even after prior NO synthase inhibition. In conclusion, endogenous endothelin
      limits pulmonary vasodilatation in response to treadmill exercise. This
      vasoconstrictor influence is blunted by NO but not by prostanoids.

PMID- 16081485
TI  - Isolation and validation of human prepubertal skeletal muscle cells: maturation
      and metabolic effects of IGF-I, IGFBP-3 and TNFalpha.
AB  - We have developed a primary skeletal muscle cell culture model derived from
      normal prepubertal children to investigate the effects of insulin-like growth
      factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and
      tumour necrosis factor alpha (TNFalpha) on growth, differentiation and
      metabolism. Cells of myoblast lineage were characterized morphologically by
      desmin staining and differentiated successfully into multinucleated myotubes.
      Differentiation was confirmed biochemically by an increase in creatine kinase
      (CK) activity and IGFBP-3 secretion over time. IGF-I promoted whilst TNFalpha
      inhibited myoblast proliferation, differentiation and IGFBP-3 secretion. IGF-I
      partially rescued the cells from the inhibiting effects of TNFalpha. Compared to
      adult myoblast cultures, children's skeletal muscle cells demonstrated higher
      basal and day 7 CK activities, increased levels of IGFBP-3 secretion, diminished
      IGF-I/TNFalpha action and absence of the inhibitory effect of exogenous IGFBP-3
      on differentiation. Additional studies demonstrated that TNFalpha increased basal
      glucose transport via GLUT1, nitric oxide synthase and p38MAPK-dependent
      mechanisms. These studies provide baseline data to study the interactivity
      effects of growth factors and cytokines on differentiation and metabolism in
      muscle in relation to important metabolic disorders such as obesity, type II
      diabetes or chronic wasting diseases.

PMID- 16081486
TI  - The effect of low protein diet in pregnancy on the development of brain
      metabolism in rat offspring.
AB  - The effect of maternal low protein diet in pregnancy on the function of offspring
      cerebral cytochrome c oxidase (CcO) was investigated in vitro immediately before
      and after birth, using fetal and neonatal rat pup forebrain tissue. Pregnant rat
      dams were fed either a control (C, 18% casein n = 22) or low protein (LP, 9%
      casein n = 14) diet. Cerebral tissues were harvested from pups the day before
      (E21) and after (P1) birth. A Clarke electrode chamber was used to determine O(2)
      consumption in brain tissue homogenate, under baseline conditions with and
      without the mitochondrial electron transport chain inhibitor myxothiazol and in
      the presence of incremental doses of the electron donor N',N',N',N'-tetramethyl-p
      phenylenediamide (TMPD) with myxothiazol. Maximal stimulated CcO activity was
      less in LP versus C pups at both E21 (P < 0.001) and P1 (P < 0.05). At E21 only,
      sensitivity to electron flux (pEC(50)) was greater (P < 0.001) in LP compared to
      C offspring. In addition, was reduced and pEC(50) was greater after birth (i.e.
      P1 versus E21) in C (P < 0.001) but not in LP pups. This is the first report of
      the effects of maternal dietary imbalance in pregnancy on offspring cerebral
      metabolic function. The effects may form part of a developmental adaptive
      response to reduce energy consumption and promote perinatal survival, or to
      confer advantage in a postnatal environment predicted to be nutritionally poor.

PMID- 16081487
TI  - Neuropeptide Y bioavailability is suppressed in the hindlimb of female Sprague
      Dawley rats.
AB  - We recently reported that male, but not female, rats exhibit basal endogenous
      neuropeptide Y Y(1)-receptor modulation of hindlimb vasculature. The lack of
      baseline endo-genous Y(1)-receptor control in females was evident despite the
      expression of Y(1)-receptors and neuropeptide Y in hindlimb skeletal muscle
      tissue. The following study addressed the hypothesis that neuropeptide Y
      bioavailability is blunted in female rats under baseline conditions. It was
      further hypothesized that enhanced prejunctional autoinhibitory neuropeptide Y
      Y(2)-receptor expression and/or proteolytic processing of released neuropeptide Y
      may persist in female rats. Using western blot analysis, it was observed that
      females had greater overall neuropeptide Y Y(2)-receptor expression in skeletal
      muscle compared to males (P < 0.05). To address the prevalence/impact of baseline
      endogenous Y(2)-receptor activation on neuropeptide Y release in hindlimb
      vasculature, an arterial infusion of BIIE0246 (specific non-peptide Y(2)-receptor
      antagonist; 170 microg kg(-1)) was carried out on female and male rats. Y(2)
      receptor blockade resulted in a decrease in hindlimb vascular conductance in
      females and males (P < 0.05). However, the BIIE0246-induced decrease in vascular
      conductance was Y(1)-receptor dependent in females, but not males (P < 0.05). In
      addition, compared to baseline, BIIE0246 infusion resulted in increased plasma
      neuropeptide Y concentration in females (P < 0.05), while there was no observable
      change in males. In a final experiment, systemic inhibition of proteolytic
      enzymes dipeptidylpeptidase IV (via 500 nM diprotin A) and aminopeptidase P (via
      180 nM 2-mercaptoethanol) elicited a Y(1)-receptor-dependent decrease in hindlimb
      vascular conductance in females (P < 0.05). It was concluded that our previously
      reported lack of basal endogenous Y(1)-receptor activation in female hindlimb
      vasculature was (at least partially) due to prejunctional Y(2)-receptor
      autoinhibition and proteolytic processing of neuropeptide Y.

PMID- 16081488
TI  - Activation of olfactory-type cyclic nucleotide-gated channels is highly
      cooperative.
AB  - Cyclic nucleotide-gated (CNG) ion channels play a key role in the sensory
      transduction of vision and olfaction. The channels are opened by the binding of
      cyclic nucleotides. Native olfactory CNG channels are heterotetramers of CNGA2,
      CNGA4, and CNGB1b subunits. Upon heterologous expression, only CNGA2 subunits can
      form functional homotetrameric channels. It is presently not known how the
      binding of the ligands to the four subunits is translated to channel opening. We
      studied activation of olfactory CNG channels by photolysis-induced jumps of cGMP
      or cAMP, two cyclic nucleotides with markedly different apparent affinity. It is
      shown that at equal degree of activation, the activation time course of
      homotetrameric channels is similar with cGMP and cAMP and it is also similar in
      homo- and heterotetrameric channels with the same cyclic nucleotide. Kinetic
      models were globally fitted to activation time courses of homotetrameric
      channels. While all models containing equivalent binding sites failed, a model
      containing three binding sites with a ligand affinity high-low-high described the
      data adequately. Only the second binding step switches from a very low to a very
      high open probability. We propose a unique gating mechanism for homotetrameric
      and heterotetrameric channels that involves only three highly cooperative binding
      steps.

PMID- 16081489
TI  - Molecular mechanisms of regulation of fast-inactivating voltage-dependent
      transient outward K+ current in mouse heart by cell volume changes.
AB  - The K(v)4.2/4.3 channels are the primary subunits that contribute to the fast
      inactivating, voltage-dependent transient outward K(+) current (I(to,fast)) in
      the heart. I(to,fast) is the critical determinant of the early repolarization of
      the cardiac action potential and plays an important role in the adaptive
      remodelling of cardiac myocytes, which usually causes cell volume changes, during
      myocardial ischaemia, hypertrophy and heart failure. It is not known, however,
      whether I(to,fast) is regulated by cell volume changes. In this study we
      investigated the molecular mechanism for cell volume regulation of I(to,fast) in
      native mouse left ventricular myocytes. Hyposmotic cell swelling caused a marked
      increase in densities of the peak I(to,fast) and a significant shortening in
      phase 1 repolarization of the action potential duration. The voltage-dependent
      gating properties of I(to,fast) were, however, not altered by changes in cell
      volume. In the presence of either protein kinase C (PKC) activator (12,13
      dibutyrate) or phosphatase inhibitors (calyculin A and okadaic acid), hyposmotic
      cell swelling failed to further up-regulate I(to,fast). When expressed in NIH/3T3
      cells, both K(v)4.2 and K(v)4.3 channels were also strongly regulated by cell
      volume in the same voltage-independent but PKC- and phosphatase-dependent manner
      as seen in I(to,fast) in the native cardiac myocytes. We conclude that
      K(v)4.2/4.3 channels in the heart are regulated by cell volume through a
      phosphorylation/dephosphorylation pathway mediated by PKC and serine/threonine
      phosphatase(s). These findings suggest a novel role of K(v)4.2/4.3 channels in
      the adaptive electrical and structural remodelling of cardiac myocytes in
      response to myocardial hypertrophy, ischaemia and reperfusion.

PMID- 16081490
TI  - Effects of nitric oxide synthase inhibition by L-NAME on oxygen uptake kinetics
      in isolated canine muscle in situ.
AB  - Nitric oxide (NO) has an inhibitory action on O2 uptake (VO2) at the level of the
      mitochondrial respiratory chain. The aim of this study was to evaluate the
      effects of NO synthase (NOS) inhibition on muscle (VO2) kinetics. Isolated canine
      gastrocnemius muscles in situ (n = 6) were studied during transitions from rest
      to 4-min of electrically stimulated contractions corresponding to approximately
      60% of the muscle peak . Two conditions were compared: (i) Control (CTRL) and
      (ii) L-NAME, in which the NOS inhibitor L-NAME (20 mg kg(-1)) was administered.
      In both conditions the muscle was pump-perfused with constantly elevated blood
      flow (Q), at a level measured during a preliminary contraction trial with
      spontaneous self-perfused (Q). A vasodilatory drug was also infused. Arterial and
      venous O2 concentrations were determined at rest and at 5-7 s intervals during
      the transition. VO2 was calculated by Fick's principle. Muscle biopsies were
      obtained at rest and during contractions. Muscle force was measured continuously.
      Phosphocreatine hydrolysis and the calculated substrate level phosphorylation
      were slightly (but not significantly) lower in L-NAME than in CTRL. Significantly
      (P < 0.05) less fatigue was found in L-NAME versus CTRL. The time delay (TD(f))
      and the time constant (tau(f)) of the 'fundamental' component of VO2 kinetics
      were not significantly different between CTRL (TD(f) 7.2 +/- 1.2 s; and tau(f)
      10.6 +/- 1.3, +/- s.e.m.) and L-NAME (TD(f) 9.3 +/- 0.6; and tau(f) 10.4 +/-
      1.0). Contrary to our hypothesis, NOS inhibition did not accelerate muscle VO2
      kinetics. The down-regulation of mitochondrial respiration by NO does not limit
      the kinetics of adjustment of oxidative metabolism at exercise onset.

PMID- 16081491
TI  - AC electric fields and particle deposition on a sphere.
AB  - The National Radiological Protection Board's Independent Advisory Group on Non
      ionising Radiation considered the possible effects on health of particle
      deposition in the vicinity of power lines and recommended, inter alia, that
      further studies were needed to reduce the uncertainties regarding the dependence
      of deposition on particle size and air flow. Empirical heat transfer data have
      been used to estimate the effects of thermophoresis on particle deposition on a
      sphere mimicking the human head. It is shown that these effects become
      significant for particle diameters >6 nm and skin temperature needs to be
      considered when modelling the deposition of larger particles. If one assumes that
      deposition takes place to smooth surfaces under isothermal conditions, the model
      predicts, in line with the calculations of Fews et al., that exposure to a power
      line electric field will enhance deposition (relative to that from diffusion)
      throughout the size range up to 10 mum. However, such models do not represent
      deposition on the skin because of the neglect of the effects of surface
      temperature and texture. Previous workers have measured the ratio of deposition
      with and without electric field exposure. It is suggested that this is a
      misleading parameter and data should be presented in terms of the collection
      efficiencies, which are proportional to the actual amount deposited.

PMID- 16081492
TI  - Assessment of plutonium exposures for an epidemiological study of US nuclear
      workers.
AB  - An ongoing case-control study evaluating the association between workplace
      external radiation exposures and leukaemia mortality required an assessment of
      internal plutonium exposures as a potential confounder. Of the study
      participants, 1,092 were employed at four Department of Energy sites where
      plutonium-bearing materials were processed or stored. Exposures were assessed by
      first categorising exposure potentials based on available bioassay data, then
      estimating doses for workers in the highest categories using recent
      recommendations of the International Commission on Radiological Protection. Given
      the aetiology of leukaemia, equivalent dose to active bone marrow was chosen as
      the exposure variable. There were 556 workers each with at least one plutonium
      bioassay result, assigned to one of three evaluation categories. Dose estimates
      were made for 115 workers resulting in a collective equivalent dose of 2.1 person
      Sv for 2,822 exposure-years, compared with 29.8 person-Sv estimated from photon
      exposures. Modelling uncertainties were examined by comparison of results from
      independent analyses and by Monte Carlo simulation.

PMID- 16081493
TI  - Miners' exposure to radon and its decay products in some Iranian non-uranium
      underground mines.
AB  - Measurements of radon, radon decay products and gamma exposure rate in 12 non
      uranium underground mines have been carried out in order to estimate the
      occupational radiation exposure of miners. Continuous measurements of radon using
      pulse ionisation chambers and scintillation cell techniques were employed for
      these studies. Progenies of radon were collected on filter paper, and then a
      three-count procedure was used for the measurement. The equilibrium state between
      radon and its decay products has been determined. Concentrations of natural
      radionuclides ((226)Ra, (232)Th and (40)K) in ore and soil samples taken from
      various locations in each mine have been measured using a Canberra High Purity
      Germanium detector. Based on these measurements two ranges of dose were evident.
      Doses ranged from 0.1 to 1.52 mSv y(-1) for nine mines and from 10 to 31 mSv y(
      1) for the other three mines. A separate grouping of the mines was recognised
      from radon concentrations, which varied from 2 Bq m(-3) to 10 kBq m(-3). In three
      of these mines, working level (WL) concentrations of the order of 36-1771 mWL
      were determined in different working areas. In all other mines, the
      concentrations were observed to be <45 mWL.

PMID- 16081494
TI  - Radiation exposure and cause specific mortality among nuclear workers in Belgium
      (1969-1994).
AB  - Cause specific mortality was studied in nuclear workers from five nuclear
      facilities in Belgium and compared to the general population. For the 1969-1994
      period, mortality in male nuclear workers is significantly lower for all causes
      of death and for all cancer deaths. The same conclusions are reached if one
      assumes a latency period of 20 y between the first irradiation and cancer
      induction. In female workers, mortality due to all causes and all cancer deaths
      is not different from that of the general population. Analysis of cause specific
      mortality was performed for male and female workers for three endpoints: specific
      cancer sites, cardiovascular and respiratory diseases. No significant increase in
      mortality was observed. In male workers, the influence of cumulative dose was
      also investigated using four dose levels: no significant correlation was found.
      Smoking habits may be a confounding factor in smoking related health conditions.

PMID- 16081495
TI  - Evidence of hybridization between Lythrum salicaria (purple loosestrife) and L.
      alatum (winged loosestrife) in North America.
AB  - BACKGROUND AND AIMS: Although Lythrum salicaria (purple loosestrife) was
      introduced to North America from Europe in the early 1800s, it did not become
      invasive until the 1930s. Whether hybridization with L. alatum (winged
      loosestrife) could have played a role in its ultimate spread was tested. METHODS:
      Six diagnostic morphological traits (flower number per axil, leaf placement,
      calyx pubescence, style type, plant height and leaf shape) were surveyed in 30
      populations of Lythrum across eastern North America. Patterns of AFLP variation
      were also evaluated using five primer pairs in a 'global screen' of the same
      North American populations of L. salicaria and L. alatum described above, in L.
      salicaria from 11 European populations located in Germany, England, Ireland,
      Austria and Finland, and in six L. salicaria cultivars. KEY RESULTS: All of the
      North American L. salicaria populations had individuals with alternate leaf
      placement and 1-2 flowers per leaf axil, which have not been described in
      Eurasian L. salicaria but predominate in North American L. alatum. In addition,
      two L. salicaria populations were intermediate in height and leaf ratio between
      the typical L. salicaria and L. alatum populations in their native fields and
      when grown in a common greenhouse. In screens of variation patterns using 279
      AFLPs, only two fragments were found that clearly supported introgression from L.
      alatum to L. salicaria. CONCLUSIONS: The evidence indicates that L. salicaria may
      have hybridized with L. alatum, but if so, only a small fraction of L. alatum
      genes have been retained in the genome of L. salicaria. This is unlikely to have
      led to a dramatic adaptive shift unless the introgression of a few key genes into
      L. salicaria stimulated a genomic reorganization. It is more likely that crossing
      among genotypes of L. salicaria from multiple introductions provided the
      necessary variability for new adaptations to arise.

PMID- 16081496
TI  - Genome-wide analysis of transcript abundance and translation in Arabidopsis
      seedlings subjected to oxygen deprivation.
AB  - BACKGROUND AND AIMS: DNA microarrays allow comprehensive estimation of total
      cellular mRNA levels but are also amenable to studies of other mRNA populations,
      such as mRNAs in translation complexes (polysomes). The aim of this study was to
      evaluate the role of translational regulation in response to oxygen deprivation
      (hypoxia). METHODS: Alterations in total cellular and large polysome (>or=five
      ribosomes per mRNA) mRNA levels were monitored in response to 12 h of hypoxia
      stress in seedlings of Arabidopsis thaliana with a full-genome oligonucleotide
      microarray. KEY RESULTS: Comparison of two mRNA populations revealed considerable
      modulation of mRNA accumulation and diversity in translation in response to
      hypoxia. Consistent with the global decrease in protein synthesis, hypoxia
      reduced the average proportion of individual mRNA species in large polysome
      complexes from 56.1% to 32.1%. A significant decrease in the association with
      translational complexes was observed for 77% of the mRNAs, including a subset of
      known hypoxia-induced gene transcripts. The examination of mRNA levels of nine
      genes in polysomes fractionated through sucrose density gradients corroborated
      the microarray data. Gene cluster analysis was used to identify mRNAs that
      displayed co-ordinated regulation. Fewer than half of the highly induced mRNAs
      circumvented the global depression of translation. Moreover, a large number of
      mRNAs displayed a significant decrease in polysome association without a
      concomitant decrease in steady-state accumulation. The abundant mRNAs that encode
      the ribosomal proteins behaved in this manner. By contrast, a small group of
      abiotic and biotic stress-induced mRNAs showed a significant increase in polysome
      association, without a change in abundance. Evaluation of quantitative features
      of mRNA sequences demonstrated that a low GC nucleotide content of the 5'
      untranslated region provides a selective advantage for translation under hypoxia.
      CONCLUSIONS: Alterations in transcript abundance and translation contribute to
      the differential regulation of gene expression in response to oxygen deprivation.

PMID- 16081497
TI  - A re-examination of the root cortex in wetland flowering plants with respect to
      aerenchyma.
AB  - AIMS: We review literature and present new observations on the differences among
      three general patterns of aerenchyma origin and their systematic distributions
      among the flowering plants, and we clarify terminology on root aerenchyma. SCOPE:
      From our own previous works and some new observations, we have analysed the root
      cortex in 85 species of 41 families in 21 orders of flowering plants that
      typically grow in wetlands to determine the characteristic patterns of
      aerenchyma. FINDINGS: A developmental and structural pattern that we term
      expansigeny, as manifested by honeycomb aerenchyma, is characteristic of all
      aquatic basal angiosperms (the Nymphaeales) and basal monocots (the Acorales).
      Expansigenous aerenchyma develops by expansion of intercellular spaces into
      lacunae by cell division and cell expansion. Schizogeny and lysigeny, so often
      characterized in recent reviews as the only patterns of root cortex lacunar
      formation, are present in most wetland plants, but are clearly not present in the
      most basal flowering plants. CONCLUSION: We conclude that expansigeny is the
      basic type of aerenchyma development in roots of flowering plants and that the
      presence of expansigenous honeycomb aerenchyma in root cortices was fundamental
      to the success of the earliest flowering plants found in wetland environments.

PMID- 16081498
TI  - The complex world of military medicine: a conversation with William Winkenwerder.
      Interview by Robert Galvin.
AB  - Starting as assistant secretary of defense for health affairs just ten days after
      the 9/11 terrorist attacks, William Winkenwerder has probably the most complex
      and challenging leadership role in health care. In this interview he talks about
      the innovations taking place in battlefield medicine; the cost pressures and
      consolidation that exist in the military health system; the challenges of
      reporting to his notoriously demanding boss, Secretary of Defense Donald
      Rumsfeld; and the need to deal with a questioning, skeptical media. Trained in
      internal medicine and business administration, Winkenwerder came to the Defense
      Department after stints at Emory University and Blue Cross of Massachusetts.

PMID- 16081499
TI  - Erythropoietin receptor spliced forms differentially expressed in blind
      subterranean mole rats.
AB  - Erythropoietin (Epo) is the primary regulator of erythropoiesis, controlling the
      proliferation, maturation, and survival of erythroid progenitor cells. The
      functions of Epo are mediated through its specific receptor (EpoR) expressed
      mainly on the surface of erythroid progenitor cells, and the expression of both
      responds to hypoxia. The subterranean mole rat (Spalax) is a unique model system
      to study the molecular mechanisms for adaptation to hypoxia. Here, we cloned two
      forms of Spalax EpoR: a complete EpoR cDNA as well as a novel truncated bone
      marrow specific EpoR form. In the full-length Spalax EpoR (sEpoR), two out of the
      eight conserved tyrosine- phosphorylation sites were substituted (Y481F and
      Y499G), suggesting that Spalax Epo signaling pathways may be modulated. The level
      of the sEpoR mRNA in the spleen and in bone marrow was relatively low and similar
      in Spalax newborns and adults, with no significant response to hypoxia. The
      truncated sEpoR was not detected in the spleen and comprised only approximately
      1% of the sEpoR expressed in the bone marrow. In Rattus, the truncated EpoR form
      was approximately 15% of the total expressed receptor. The level of Rattus EpoR
      in newborn spleens was three- to fourfold higher than in Spalax newborns and
      decreased toward adulthood. Severe hypoxia induces a significant increase in
      adult Rattus EpoR. Our data provide further insight into the adaptive mechanisms
      of Spalax to the extreme conditions of hypoxia in its subterranean environment.

PMID- 16081500
TI  - An alternative Ca2+-dependent mechanism of neuroprotection by the
      metalloporphyrin class of superoxide dismutase mimetics.
AB  - This study challenges the conventional view that metalloporphyrins protect
      cultured cortical neurons in models of cerebral ischemia by acting as
      intracellular catalytic antioxidants [superoxide dismutase (SOD) mimetics]. High
      SOD-active Mn(III)porphyrins meso-substituted with N,N'-dimethylimidazolium or N
      alkylpyridinium groups did not protect neurons against oxygen-glucose deprivation
      (OGD), although lower SOD-active and -inactive para isomers protected against N
      methyl-D-aspartate (NMDA) exposure. Mn(III)meso-tetrakis(4-benzoic acid)porphyrin
      (Mn(III)TBAP), as well as SOD-inactive metalloTBAPs and other phenyl ring- or
      beta-substituted metalloporphyrins that contained redox-insensitive metals,
      protected cultures against OGD and NMDA neurotoxicity. Crucially, neuroprotective
      metalloporphyrins suppressed OGD- or NMDA-induced rises in intracellular Ca2+
      concentration in the same general rank order as observed for neuroprotection.
      Results from paraquat toxicity, intracellular fluorescence quenching,
      electrophysiology, mitochondrial Ca2+, and spontaneous synaptic activity
      experiments suggest a model in which metalloporphyrins, acting at the plasma
      membrane, protect neurons against OGD by suppressing postsynaptic NMDA receptor
      mediated Ca2+ rises, thereby indirectly preventing accumulation of neurotoxic
      mitochondrial Ca2+ levels. Though neuroprotective in a manner not originally
      intended, SOD-inactive metalloporphyrins may represent promising therapeutic
      agents in diseases such as cerebral ischemia, in which Ca2+ toxicity is
      implicated. Conventional syntheses aimed at improving the catalytic antioxidant
      capability and/or intracellular access of metalloporphyrins may not yield
      improved efficacy in some disease models.

PMID- 16081501
TI  - An elevated matrix metalloproteinase (MMP) in an animal model of multiple
      sclerosis is protective by affecting Th1/Th2 polarization.
AB  - Inflammation in multiple sclerosis and its animal model, experimental autoimmune
      encephalomyelitis (EAE), is manifested by changes in matrix metalloproteinase
      (MMP) expression and in the ratio of T helper (Th) 1 and 2 effector cytokines.
      Here, we provide a comprehensive documentation of MMPs in EAE and report that of
      all the MMPs that could be measured at peak disease in spinal cord tissue, MMP-12
      was the most highly up-regulated. In contrast to previously published findings of
      MMPs in EAE, this increase in MMP-12 expression was associated with protection,
      as MMP-12 null mice had significantly worse maximum severity and EAE disease
      burden compared with wild-type (WT) controls. When spleen and lymph node cells
      were removed from EAE-afflicted WT and MMP-12 null mice at the same disease score
      before divergence of disease and restimulated in vitro, the MMP-12 null cells had
      significantly higher Th1 to Th2 cytokine ratio. Measurements of the
      transcriptional regulators of T cell polarization revealed that MMP-12 null cells
      had increased T-bet and reduced GATA-3 expression, a condition that favors a Th1
      bias. These results emphasize that specific MMPs can have beneficial roles in
      inflammation, and they implicate MMPs in T effector polarization for the first
      time.

PMID- 16081502
TI  - Hypoxia up-regulates expression of Eph receptors and ephrins in mouse skin.
AB  - Eph receptor tyrosine kinases and their ligands (ephrins) are key players during
      the development of the embryonic vasculature; however, their role and regulation
      in adult angiogenesis remain to be defined. Both receptors and ligands have been
      shown to be up-regulated in a variety of tumors. To address the hypothesis that
      hypoxia is an important regulator of Ephs/ephrins expression, we developed a
      mouse skin flap model of hypoxia. We demonstrate that our model truly represents
      segmental skin hypoxia by applying four independent methods: continuous
      measurement of partial cutaneous oxygen tension, monitoring of tissue
      lactate/pyruvate ratio, time course of hypoxia-inducible factor-1alpha (HIF
      1alpha) induction, and localization of stabilized HIF-1alpha by
      immunofluorescence in the hypoxic skin flap. Our experiments indicate that
      hypoxia up-regulates not only HIF-1alpha and vascular endothelial growth factor
      (VEGF) expression, but also Ephs and ephrins of both A and B subclasses in the
      skin. In addition, we show that in Hep3B and PC-3 cells, the hypoxia-induced up
      regulation of Ephs and ephrins is abrogated by small interfering RNA-mediated
      down-regulation of HIF-1alpha. These novel findings shed light on the role of
      this versatile receptor/ligand family in adult angiogenesis. Furthermore, our
      model offers considerable potential for analyzing distinct mechanisms of
      neovascularization in gene-targeted mice.

PMID- 16081503
TI  - Simultaneous multiple immunoassays in a compact disc-shaped microfluidic device
      based on centrifugal force.
AB  - BACKGROUND: We explored the potential of a microfluidic device based on
      centrifugal force as an immunoassay platform by examining the imprecision of
      assays carried out with 200 nL of sample. METHODS: Biotinylated antibodies
      against alpha-fetoprotein (AFP), interleukin-6 (IL-6), and carcinoembryonic
      antigen [(CEA); 0.1 g/L each in 15 mmol/L phosphate-buffered saline (PBS)
      containing 0.1 mL/L Tween 20] were attached to a microcolumn packed with
      streptavidin-coated particles. A 200-nL sample was then allowed to pass through
      the microcolumn for 240 s, followed by Alexa 647-labeled detection antibody (7.5
      mg/L in 15 mmol/L PBS containing 10 g/L bovine serum albumin). The flow rate was
      controlled by altering the rotational speed. Up to 104 sandwich type immunoassays
      were completed within 50 min. RESULTS: For AFP, IL-6, and CEA the detection
      limits were, respectively, 0.15, 1.25, and 1.31 pmol/L. Inter- and intraassay
      imprecisions (CVs) were <10% and <20%, respectively, for analyte concentrations
      >5 pmol/L. The CEA antibody had the lowest affinity according to fluorescence
      image analysis of the microcolumn region. The result was confirmed in a
      comparative study using BIAcore 3000. CONCLUSIONS: Day-to-day (total) imprecision
      (CV) of immunoassays on the compact disc-shaped device are <20%. Analysis of
      fluorescence images allows rapid ranking of antibodies according to their
      affinities.

PMID- 16081504
TI  - Direct quantification of analyte concentration by resonant acoustic profiling.
AB  - BACKGROUND: Acoustic sensors that exploit resonating quartz crystals directly
      detect the binding of an analyte to a receptor. Applications include detection of
      bacteria, viruses, and oligonucleotides and measurement of myoglobin, interleukin
      1beta (IL-1beta), and enzyme cofactors. METHODS: Resonant Acoustic Profiling was
      combined with a microfluidic lateral flow device incorporating an internal
      reference control, stable linker chemistry, and immobilized receptors on a
      disposable sensor "chip". Analyte concentrations were determined by analyzing the
      rate of binding of the analyte to an appropriate receptor. RESULTS: The
      specificity and affinity of antibody-antigen and enzyme-cofactor interactions
      were determined without labeling of the receptor or the analyte. We measured
      protein concentrations (recombinant human IL-1beta and recombinant human
      myoglobin) and quantified binding of cofactors (NADP+ and NAD+) to the enzyme
      glucose dehydrogenase. Lower limits of detection were approximately 1 nmol/L (17
      ng/mL) for both IL-1beta and human myoglobin. The equilibrium binding constant
      for NADP+ binding to glucose dehydrogenase was 2.8 mmol/L. CONCLUSIONS: Resonant
      Acoustic Profiling detects analytes in a relatively simple receptor-binding assay
      in <10 min. Potential applications include real-time immunoassays and biomarker
      detection. Combination of this technology platform with existing technologies for
      concentration and presentation of analytes may lead to simple, label-free, high
      sensitivity methodologies for reagent and assay validation in clinical chemistry
      and, ultimately, for real-time in vitro diagnostics.

PMID- 16081505
TI  - High-resolution serum proteomic profiling of Alzheimer disease samples reveals
      disease-specific, carrier-protein-bound mass signatures.
AB  - BACKGROUND: Researchers typically search for disease markers using a "targeted"
      approach in which a hypothesis about the disease mechanism is tested and
      experimental results either confirm or disprove the involvement of a particular
      gene or protein in the disease. Recently, there has been interest in developing
      disease diagnostics based on unbiased quantification of differences in global
      patterns of protein and peptide masses, typically in blood from individuals with
      and without disease. We combined a suite of methods and technologies, including
      novel sample preparation based on carrier-protein capture and biomarker
      enrichment, high-resolution mass spectrometry, a unique cohort of well
      characterized persons with and without Alzheimer disease (AD), and powerful
      bioinformatic analysis, that add statistical and procedural robustness to
      biomarker discovery from blood. METHODS: Carrier-protein-bound peptides were
      isolated from serum samples by affinity chromatography, and peptide mass spectra
      were acquired by a matrix-assisted laser desorption/ionization (MALDI) orthogonal
      time-of-flight (O-TOF) mass spectrometer capable of collecting data over a broad
      mass range (100 to >300,000 Da) in a single acquisition. Discriminatory analysis
      of mass spectra was used to process and analyze the raw mass spectral data.
      RESULTS: Coupled with the biomarker enrichment protocol, the high-resolution
      MALDI O-TOF mass spectra provided informative, reproducible peptide signatures.
      The raw mass spectra were analyzed and used to build discriminant disease models
      that were challenged with blinded samples for classification. CONCLUSIONS:
      Carrier-protein enrichment of disease biomarkers coupled with high-resolution
      mass spectrometry and discriminant pattern analysis is a powerful technology for
      diagnostics and population screening. The mass fingerprint model successfully
      classified blinded AD patient and control samples with high sensitivity and
      specificity.

PMID- 16081506
TI  - Circulating placental RNA in maternal plasma is associated with a preponderance
      of 5' mRNA fragments: implications for noninvasive prenatal diagnosis and
      monitoring.
AB  - BACKGROUND: The molecular characteristics of placental RNA circulating in
      maternal plasma are unknown. We investigated the integrity of circulating
      placental RNA in maternal plasma and tested the relevance of plasma RNA integrity
      for noninvasive prenatal diagnosis. METHODS: Six different placental transcripts
      and mRNA of the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) were quantified for the 5' and 3' regions in maternal plasma by 1-step
      real-time reverse transcription-PCR (RT-PCR) assays. This quantitative strategy
      was validated by 2-step RT-PCR and serial dilution experiments. The rates of
      detection by the 5' and 3' assays for the beta-subunit of human chorionic
      gonadotropin (beta hCG) were assessed in maternal plasma samples collected from
      different gestational periods. RESULTS: For 5 of the 7 genes, the plasma mRNA
      concentrations measured by the 5' amplicons were significantly higher than those
      measured by the corresponding 3' amplicons. Every transcript under study
      demonstrated a higher rate of detection in the 5' assay than in the 3' assay in
      maternal plasma. In particular, the detection rate of beta hCG mRNA in maternal
      plasma was increased throughout gestation when the 5' assay was used.
      CONCLUSIONS: Circulating placental RNA is associated with a preponderance of 5'
      mRNA fragments in maternal plasma. Apart from its intrinsic biological interest,
      this information could have important implications for the development of new
      assays targeting fetal RNA markers for noninvasive prenatal diagnosis and
      monitoring.

PMID- 16081507
TI  - Simultaneous measurement of 25 inflammatory markers and neurotrophins in neonatal
      dried blood spots by immunoassay with xMAP technology.
AB  - BACKGROUND: Inflammatory reactions and other events in early life may be part of
      the etiology of late-onset diseases, including cerebral palsy, autism, and type 1
      diabetes. Most neonatal screening programs for congenital disorders are based on
      analysis of dried blood spot samples (DBSS), and stored residual DBSS constitute
      a valuable resource for research into the etiology of these diseases. The small
      amount of blood available, however, limits the number of analytes that can be
      determined by traditional immunoassay methodologies. METHODS: We used new
      multiplexed sandwich immunoassays based on flowmetric Luminex xMAP technology to
      measure inflammatory markers and neutrophins in DBSS. RESULTS: The high-capacity
      25-plex multianalyte method measured 23 inflammatory and trophic cytokines,
      triggering receptor expressed on myeloid cells-1 (TREM-1), and C-reactive protein
      in two 3.2-mm punches from DBSS. It also measured 26 cytokines and TREM-1 in
      serum. Standards Recovery in the 25-plex method were 90%-161% (mean, 105%). The
      low end of the working range for all 25 analytes covered concentrations found in
      DBSS from healthy newborns. Mean recovery of exogenous analytes added at
      physiologic concentrations in DBSS models was 174%, mean intra- and interassay
      CVs were 6.2% and 16%, respectively, and the mean correlation between added and
      measured analytes was r2 = 0.91. In DBSS routinely collected on days 5-7 from 8
      newborns with documented inflammatory reactions at birth, the method detected
      significantly changed concentrations of inflammatory cytokines. Measurements on
      DBSS stored at -24 degrees C for >20 years showed that most cytokines are
      detectable in equal concentrations over time. CONCLUSIONS: The method can
      reliably measure 25 inflammatory markers and growth factors in DBSS. It has a
      large potential for high-capacity analysis of DBSS in epidemiologic case-control
      studies and, with further refinements, in neonatal screening.

PMID- 16081508
TI  - Surfactant-based homogeneous assay for the measurement of triglyceride
      concentrations in VLDL and intermediate-density lipoprotein.
AB  - BACKGROUND: Existing studies have demonstrated the clinical significance of
      triglyceride content in VLDL (VLDL-TG) and intermediate-density lipoprotein (IDL
      TG). We developed a homogeneous assay protocol to directly measure VLDL-TG.
      METHODS: Possible reagents and conditions for measuring VLDL-TG were
      comprehensively tested, and the "best" combination was determined. Healthy
      persons were instructed to consume a fatty meal after 15-h overnight fasting.
      Serum VLDL-TG + IDL-TG concentrations were measured using the proposed method.
      Patients with serum LDL-cholesterol concentrations > or = 3.62 mmol/L (140 mg/dL)
      were administered simvastatin at a daily dose of 5 mg, and serum VLDL-TG
      concentrations were then measured. RESULTS: The combination of 2 nonionic
      surfactants played an important role in differentiating VLDL and IDL from other
      lipoproteins, probably via specific interactions with phospholipids and
      apolipoproteins. The regression line of the proposed method (y) and the
      ultracentrifugal assay (x) was: y = 0.98x + 0.31 mmol/L (r = 0.98; n = 73; P <
      0.05). The difference between postprandial total TG and VLDL-TG concentrations
      was statistically significant (P < 0.05). After 8 weeks of therapy with
      simvastatin, total TG and LDL-cholesterol concentrations were 13.6% and 26.3%
      lower, respectively (P < 0.05), whereas VLDL-TG did not show any significant
      decrease. CONCLUSION: Our homogeneous method can measure TG content in VLDL and
      IDL.

PMID- 16081509
TI  - Association between the neuregulin 1 gene and schizophrenia: a systematic review.
AB  - Chromosome 8p22-p11 has been identified as a locus for schizophrenia in several
      genome-wide scans, which has been confirmed by meta-analysis of published linkage
      data. It appears to be 1 of the most robust linkage findings in psychosis.
      Several attempts have been made to identify the underlying genetic variation that
      gives rise to this linkage peak, including systematic fine mapping using extended
      Icelandic pedigrees that have identified an associated haplotype (HAP(ICE)) in
      the gene neuregulin 1, also known as heuregulin, glial growth factor, NDF43, and
      ARIA. Neuregulin 1 (NRG1) is a plausible susceptibility gene because of its
      involvement in neurodevelopment, regulation of glutamate and other
      neurotransmitter receptor expression, and synaptic plasticity. Encouragingly,
      this finding was quickly and directly replicated in a Scottish case-control
      sample by the same investigators with the same approximately 300 kb associated
      haplotype. Although in Caucasian populations subsequent attempts at replication
      of this finding have been difficult to interpret, and no individual functional or
      causative genetic variants have yet been identified, a summary of HAP(ICE)
      association results in about 4,500 subjects is consistent with a small (odds
      ratio approximately 1.5) but significant effect of this haplotype on
      schizophrenia risk. In Chinese Han populations, where HAP(ICE) is not found,
      there is good evidence from several studies of association with other markers in
      the same region. Overall, there is convincing but not yet compelling evidence for
      a role for NRG1 in susceptibility to schizophrenia. Other genes from this region
      have also been implicated in schizophrenia, not by systematic mapping but by
      positional candidate gene analysis; these include MSTP131, frizzled-3, and the
      calcineurin A gamma subunit gene. Not only are these alternative explanations for
      the linkage seen between chromosome 8p and schizophrenia, but it is equally
      possible that there is more than 1 susceptibility gene at this locus.

PMID- 16081510
TI  - Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common
      catechol-containing coffee polyphenols.
AB  - We studied the modulating effects of caffeic acid and chlorogenic acid (two
      common coffee polyphenols) on the in vitro methylation of synthetic DNA
      substrates and also on the methylation status of the promoter region of a
      representative gene in two human cancer cells lines. Under conditions that were
      suitable for the in vitro enzymatic methylation of DNA and dietary catechols, we
      found that the presence of caffeic acid or chlorogenic acid inhibited in a
      concentration-dependent manner the DNA methylation catalyzed by prokaryotic
      M.SssI DNA methyltransferase (DNMT) and human DNMT1. The IC50 values of caffeic
      acid and chlorogenic acid were 3.0 and 0.75 microM, respectively, for the
      inhibition of M.SssI DNMT-mediated DNA methylation, and were 2.3 and 0.9 microM,
      respectively, for the inhibition of human DNMT1-mediated DNA methylation. The
      maximal in vitro inhibition of DNA methylation was approximately 80% when the
      highest concentration (20 microM) of caffeic acid or chlorogenic acid was tested.
      Kinetic analyses showed that DNA methylation catalyzed by M.SssI DNMT or human
      DNMT1 followed the Michaelis-Menten curve patterns. The presence of caffeic acid
      or chlorogenic acid inhibited DNA methylation predominantly through a non
      competitive mechanism, and this inhibition was largely due to the increased
      formation of S-adenosyl-L-homocysteine (SAH, a potent inhibitor of DNA
      methylation), resulting from the catechol-O-methyltransferase (COMT)-mediated O
      methylation of these dietary catechols. Using cultured MCF-7 and MAD-MB-231 human
      breast cancer cells, we also demonstrated that treatment of these cells with
      caffeic acid or chlorogenic acid partially inhibited the methylation of the
      promoter region of the RARbeta gene. The findings of our present study provide a
      general mechanistic basis for the notion that a variety of dietary catechols can
      function as inhibitors of DNA methylation through increased formation of SAH
      during the COMT-mediated O-methylation of these dietary chemicals.

PMID- 16081511
TI  - Strain differences in the susceptibility to azoxymethane and dextran sodium
      sulfate-induced colon carcinogenesis in mice.
AB  - We have recently developed a mouse model for colitis-related colon carcinogenesis
      by a combined treatment with azoxymethane (AOM) and dextran sodium sulfate (DSS)
      in male ICR mice. However, strain differences in the sensitivity to AOM/DSS
      induced colon carcinogenesis in mice have yet to be elucidated. The aim of this
      study was to determine the presence of any genetically determined differences in
      sensitivity to our model of colon carcinogenesis in four inbred strains of mice.
      Male Balb/c, C3H/HeN, C57BL/6N and DBA/2N mice were given a single
      intraperitoneal injection of AOM (10 mg/kg body wt), followed by 1% DSS (w/v) in
      drinking water for 4 days, and thereafter they received no further treatment for
      up to 16 weeks. At the end of the study (Week 18), all mice were killed and a
      histopathological analysis of their colon was performed. The incidence of colonic
      adenocarcinoma was 100% with a multiplicity (no. of tumors/mouse) of 7.7+/-4.3 in
      the Balb/c mice and 50% with a multiplicity of 1.0+/-1.2 in the C57BL/6N mice. On
      the other hand, only a few colonic adenomas, but no adenocarcinomas, developed in
      the C3H/HeN mice (29% incidence with a multiplicity of 0.7+/-1.5) and the DBA/2N
      mice (20% incidence with a multiplicity of 0.2+/-0.4). The inflammation and
      immunohistochemical nitrotyrosine-positivity scores of the mice treated with AOM
      and DSS in the decreasing order were as follows: C3H/HeN>Balb/c>DBA/2N>C57BL/6N
      and Balb/c>C57BL/6N>C3H/HeN>DBA/2N, respectively. Our results thus indicated the
      presence of strain differences in the susceptibility to AOM/DSS-induced colonic
      tumorigenesis. These differences may have been directly influenced by the
      response to nitrosation stress due to the inflammation caused by DSS.

PMID- 16081512
TI  - Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma
      pigmentosum patients.
AB  - Xeroderma pigmentosum group C (XP-C) is a rare autosomal recessive disorder.
      Patients with two mutant alleles of the XPC DNA repair gene have sun sensitivity
      and a 1000-fold increase in skin cancers. Clinically normal parents of XP-C
      patients have one mutant allele and one normal allele. As a step toward
      evaluating cancer risk in these XPC heterozygotes we characterized cells from 16
      XP families. We identified 15 causative mutations (5 frameshift, 6 nonsense and 4
      splicing) in the XPC gene in cells from 16 XP probands. All had premature
      termination codons (PTC) and absence of normal XPC protein on western blotting.
      The cell lines from 26 parents were heterozygous for the same mutations. We
      employed a real-time quantitative reverse transcriptase-PCR assay as a rapid and
      sensitive method to measure XPC mRNA levels. The mean XPC mRNA levels in the cell
      lines from the XP-C probands were 24% (P<10(-7)) of that in 10 normal controls.
      This reduced XPC mRNA level in cells from XP-C patients was caused by the PTC
      that induces nonsense-mediated mRNA decay. The mean XPC mRNA levels in cell lines
      from the heterozygous XP-C carriers were intermediate (59%, P=10(-4)) between the
      values for the XP patients and the normal controls. This study demonstrates
      reduced XPC mRNA levels in XP-C patients and heterozygotes. Thus, XPC mRNA levels
      may be evaluated as a marker of cancer susceptibility in carriers of mutations in
      the XPC gene.

PMID- 16081513
TI  - Antitumor effect of parathyroid hormone-related protein neutralizing antibody in
      human renal cell carcinoma in vitro and in vivo.
AB  - Functional inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene
      occurs in 40-80% of human conventional renal cell carcinomas (RCCs). We showed
      recently that VHL-deficient RCCs expressed large amounts of parathyroid hormone
      related protein (PTHrP), and that PTHrP, acting through the PTH1 receptor
      (PTH1R), plays an essential role in tumor growth. We also showed that PTHrP
      expression is negatively regulated by the VHL gene products (pVHL). Our goal was
      to determine whether blocking the PTHrP/PTH1R system might be of therapeutic
      value against RCC, independent of VHL status and PTHrP expression levels. The
      antitumor activity of PTHrP neutralizing antibody and of PTH1R antagonist were
      evaluated in vitro and in vivo in a panel of human RCC lines expressing or not
      pVHL. PTHrP is upregulated compared with normal tubular cells. In vitro, tumor
      cell growth and viability was decreased by up to 80% by the antibody in all cell
      lines. These effects resulted from apoptosis. Exogenously added PTHrP had no
      effect on cell growth and viability, but reversed the inhibitory effects of the
      antibody. The growth inhibition was reproduced by a specific PTH1R antagonist in
      all cell lines. In vivo, the treatment of nude mice bearing the Caki-1 RCC tumor
      with the PTHrP antibody inhibited tumor growth by 80%, by inducing apoptosis.
      Proliferation and neovascularization were not affected by the antiserum. Anti
      PTHrP treatment induced no side effects as assessed by animal weight and blood
      chemistries. Current therapeutic strategies are only marginally effective against
      metastatic RCC, and adverse effects are common. This study provides a rationale
      for evaluating the blockade of PTHrP signaling as therapy for human RCC in a
      clinical setting.

PMID- 16081514
TI  - Non-parenchymal liver cells support the growth advantage in the first stages of
      hepatocarcinogenesis.
AB  - Hepatocellular carcinoma almost always arises in chronically inflamed livers. We
      developed a culture model to study the role of non-parenchymal cells (NPCs) for
      inflammation-driven hepatocarcinogenesis. Rats were treated with the carcinogen N
      nitrosomorpholine, which induced initiated hepatocytes expressing the marker
      placental glutathione-S-transferase (GSTp). After 21 days two preparations of
      hepatocytes were made: (i) conventional ones (Hep-conv) containing NPCs and (ii)
      hepatocytes purified of NPCs (Hep-pur). Initiated hepatocytes, being positive for
      GSTp (GSTp-pos) were present in both preparations and were cultured along with
      normal hepatocytes, being negative for GSTp (GSTp-neg). Under any culture
      condition DNA synthesis was approximately 4-fold higher in GSTp-pos than in GSTp
      neg hepatocytes demonstrating the inherent growth advantage of the first stages
      of hepatocarcinogenesis. Hepatocytes showed approximately 3-fold lower rates of
      DNA synthesis in Hep-pur than in Hep-conv, which was elevated above Hep-conv
      levels by addition of NPC or NPC-supernatant. Pretreatment of NPCs with
      proinflammatory lipopolysaccharide (LPS) further increased DNA synthesis. Thus,
      NPCs release soluble growth stimulators. Next we investigated the effect of
      specific cytokines produced by NPCs. Tumour necrosis factor alpha and interleukin
      6 barely altered DNA synthesis, whereas hepatocyte growth factor (HGF),
      keratinocyte growth factor (KGF) and the heparin-binding epidermal growth factor
      like growth factor (HB-EGF) were potent inducers of DNA replication in both, GSTp
      neg and GSTp-pos cells. In conclusion, DNA synthesis of hepatocytes is increased
      by factors released from NPCs, an effect augmented by LPS-stimulation. NPC
      derived cytokines, such as KGF, HGF and HB-EGF, stimulate DNA synthesis
      preferentially in initiated hepatocytes, presumably resulting in tumour
      promotion. Similar mechanisms may contribute to carcinogenesis in human
      inflammatory liver diseases.

PMID- 16081515
TI  - Promoter-hypermethylation is causing functional relevant downregulation of
      methylthioadenosine phosphorylase (MTAP) expression in hepatocellular carcinoma.
AB  - The methylthioadenosine phosphorylase (MTAP) gene is localized in the chromosomal
      region 9p21. Here, frequently homozygous deletions occur in several kinds of
      cancer associated with the loss of tumour suppressor genes as p16 and p15. The
      aim of this study was to analyse MTAP expression in hepatocellular carcinoma
      (HCC) and to get an insight into the regulation and functional role of MTAP in
      hepatocancerogenesis. Compared with primary human hepatocytes MTAP expression was
      markedly downregulated in three different HCC cell lines as determined by real
      time PCR and western blotting. This was not due to genomic losses or mutations
      but to promoter-hypermethylation. Reduced MTAP-expression was confirmed in vivo
      in HCC compared with non-cancerous liver tissue on both mRNA and protein levels.
      To study the functional relevance of the downregulated MTAP expression in HCC,
      MTAP expression was re-induced in HCC cell lines by stable transfection. In these
      MTAP re-expressing cell clones the invasive potential was strongly reduced,
      whereas no effects on cell proliferation were observed in comparison with mock
      transfected cell clones. Furthermore, in MTAP re-expressing cells interferon
      (IFN)-alpha and IFN-gamma induced a significantly stronger inhibition of cell
      proliferation than in mock transfected cells. In conclusion, our results suggest
      a functional role of MTAP inactivation in HCC development and invasiveness.
      Furthermore, in the light of a recent report revealing an association between
      MTAP activity and IFN sensitivity, our findings may have clinical significance
      for therapeutic strategies.

PMID- 16081516
TI  - Unique domain functions of p63 isotypes that differentially regulate distinct
      aspects of epidermal homeostasis.
AB  - p63 is critical for squamous development and exists as multiple isotypes of two
      subclasses, TA and DeltaN. DeltaNp63 isotypes can antagonize transcription by
      TAp63 and p53, and are highly expressed in squamous cell cancers. Using mouse
      keratinocytes as a biological model of squamous epithelium, we show that multiple
      p63 isotypes, DeltaN- and TA-containing, are expressed and differentially
      modulated during in vitro murine keratinocyte differentiation. DeltaNp63alpha
      declines with Ca2+-induced differentiation, while a smaller DeltaN-form,
      DeltaNp63s, persists, suggesting unique functions of the two DeltaN-forms. To
      investigate the impact of dysregulated p63 expression that is observed in cancers
      and to define the biological contribution of the different domains of the p63
      isotypes, DeltaNp63alpha, DeltaNp63p40, TAp63alpha, TAp63gamma or beta
      galactosidase were overexpressed in primary murine keratinocytes. Microarray, RT
      PCR and western blot analyses revealed that overexpression of DeltaNp63p40, which
      lacks the entire alpha-tail present in DeltaNp63alpha, permits expression of a
      full panel of differentiation markers. This is in contrast to overexpression of
      the full-length DeltaNp63alpha, which blocks induction of keratin 10, loricrin
      and filaggrin. These findings support a role for the alpha-tail of DeltaNp63alpha
      in blocking differentiation-specific gene expression. Overexpression of either
      TAp63 isotype permits keratin 10 and loricrin expression, thus the alpha-terminus
      requires the cooperation of the DeltaN domain in blocking early differentiation.
      However, both TA isotypes block filaggrin induction. The DeltaN-terminus is
      sufficient to maintain keratinocytes in a proliferative state, as both DeltaN
      forms block Ca2+-mediated p21WAF1 induction and S-phase arrest, while sustaining
      elevated PCNA levels. No alteration in cell cycle regulation was observed in
      keratinocytes overexpressing TAp63alpha or TAp63gamma. Clarifying the functional
      distinctions between p63 isotypes and domains will help to elucidate how their
      dysregulation impacts tumor biology and may suggest novel therapeutic strategies
      for modulating behavior of tumor cells with altered expression of p53 family
      members.

PMID- 16081517
TI  - Mutation of histidine 874 in the androgen receptor ligand-binding domain leads to
      promiscuous ligand activation and altered p160 coactivator interactions.
AB  - The androgen receptor (AR) signaling pathway is a major therapeutic target in the
      treatment of prostate cancer. The AR functions as a ligand-activated
      transcription factor in the presence of the cognate hormone ligands testosterone
      and dihydrotestosterone (DHT). We have characterized a highly conserved sequence
      at the C-terminal end of helix 10/11 in the ligand-binding domain (LBD), which is
      prone to receptor point mutations in prostate cancer. This sequence includes
      threonine 877 that is involved in hydrogen bonding to the D ring of the steroid
      molecule and leads to promiscuous ligand activation of the AR when mutated to
      alanine or serine. A second mutation in this region, H874Y, also results in a
      receptor protein that has broadened ligand-binding specificity, but retains an
      affinity for DHT (K(d) = 0.77 nm) similar to that of the wild-type receptor. The
      structure of the mutant LBD, expressed in Escherichia coli, is not dramatically
      altered compared with the wild-type AR-LBD in the presence of DHT, but shows a
      modestly increased sensitivity to protease digestion in the absence of hormone.
      This mutant AR showed wild-type AR-LBD/N-terminal domain interactions, but
      significantly enhanced binding and transactivation activity with all three
      members of the p160 family of coactivator proteins. Together, these phenotypic
      changes are likely to confer a selective advantage for tumor cells in a low
      androgen environment resulting from hormone therapy.

PMID- 16081518
TI  - Role of phosphoinositide signaling in the control of insulin exocytosis.
AB  - Phosphoinositides (PI) are important signaling molecules involved in the
      regulation of vesicular trafficking. We found that phosphatidylinositol 4
      phosphate (PI4P) and phosphatidylinositol 4,5-biphosphate [PI(4,5)P(2)] increase
      the secretory response triggered by 10 mum Ca(2+) in streptolysin-O-permeabilized
      insulin-secreting INS-1E cells. In addition, nutrient-induced exocytosis was
      diminished in intact cells expressing constructs that sequester PI(4,5)P(2) and
      in cells transfected with constructs that reduce by RNA interference the level of
      two enzymes involved in PI(4,5)P(2) production, type III PI4-kinase beta and type
      I phosphatidylinositol 4-bisphosphate 5-kinase-gamma. To clarify the mechanism of
      action of PI, we investigated the involvement in the regulation of insulin
      exocytosis of three potential PI targets, phospholipase D1, the Ca(2+)-dependent
      activator protein for secretion 1, and Munc18-interacting protein 1. Transfection
      of insulin-secreting cells with plasmids that direct the synthesis of small
      interfering RNAs capable of reducing the endogenous levels of these proteins
      inhibited hormone release elicited by glucose- and cAMP-elevating agents without
      affecting basal release. Our data indicate that the production of PI(4,5)P(2) is
      necessary for proper control of beta-cell secretion and suggest that at least
      part of the effect of PI on insulin exocytosis could be exerted through the
      activation of phospholipase D1, Ca(2+)-dependent activator protein for secretion
      1, and Munc18-interacting protein 1.

PMID- 16081519
TI  - Homology-modeled ligand-binding domains of zebrafish estrogen receptors alpha,
      beta1, and beta2: from in silico to in vivo studies of estrogen interactions in
      Danio rerio as a model system.
AB  - Homology models were constructed for the ligand-binding domains of zebrafish
      estrogen receptors (zfERs) alpha, beta(1), and beta(2). Estradiol-binding sites
      are nearly identical in zfERs and their human homologs, suggesting that zebrafish
      will serve as a good model system for studying human ER-binding drugs.
      Conversely, studies of endocrine disruptor effects on zebrafish will benefit from
      the wealth of data available on xenoestrogen interactions with human ERs.
      Compounds flagged by the Interagency Coordinating Committee on the Validation of
      Alternative Methods for endocrine disruptor screening were docked into our zfER
      homology models. Ideally, these in silico docking studies would be complemented
      with in vivo binding studies. To this end, fluorescently tagged estradiol was
      docked into zfERalpha and found to bind in the same manner as in human ERalpha,
      with fluorescein preferentially occupying a region between helices 11 and 12.
      Fluorescently tagged estradiol was synthesized and was found to localize along
      the path of primordial germ cell migration in the developing zebrafish embryo 3 d
      after fertilization, consistent with previous reports of 1) a role for estradiol
      in sex determination, and 2) the first appearance of ERs 2 d after fertilization.
      These data provide a foundation for future in silico and in vivo binding studies
      of estrogen agonists and antagonists with zebrafish ERs.

PMID- 16081520
TI  - Methoxychlor directly affects ovarian antral follicle growth and atresia through
      Bcl-2- and Bax-mediated pathways.
AB  - Methoxychlor (MXC) is an organochlorine pesticide and reproductive toxicant.
      While in vivo studies indicate that MXC exposure increases antral follicle
      atresia, in part by altering apoptotic regulators (Bcl-2 and Bax), they do not
      distinguish whether MXC does so via direct or indirect mechanisms. Therefore, we
      utilized an in vitro follicle culture system to test the hypothesis that MXC is
      directly toxic to antral follicles, and that overexpression of anti-apoptotic Bcl
      2, or deletion of pro-apoptotic Bax, protects antral follicles from MXC-induced
      toxicity. Antral follicles were isolated from wild-type (WT), Bcl-2
      overexpressing (Bcl-2 OE), or Bax deficient (BaxKO) mice, and exposed to
      dimethylsulfoxide (control) or MXC (1-100 microg/ml) for 96 h. Follicle diameters
      were measured every 24 h to assess growth. After 96 h, follicles were
      histologically evaluated for atresia or collected for quantitative PCR analysis
      of Bcl-2 and Bax mRNA levels. MXC (10-100 microg/ml) significantly inhibited
      antral follicle growth at 72 and 96 h, and increased atresia (100 microg/ml)
      compared to controls at 96 h. Furthermore, MXC increased Bax mRNA levels between
      48-96 h and decreased Bcl-2 mRNA levels at 96 h. While MXC inhibited growth of WT
      antral follicles beginning at 72 h, it did not inhibit growth of Bcl-2 OE or
      BaxKO follicles until 96 h. MXC also increased atresia of small and large WT and
      BaxKO antral follicles over controls, but it did not increase atresia of large
      Bcl-2 OE antral follicles over controls. These data suggest that MXC directly
      inhibits follicle growth partly by Bcl-2 and Bax pathways, and increases atresia
      partly through Bcl-2 pathways.

PMID- 16081521
TI  - A unifying concept for assessing toxicological interactions: changes in slope.
AB  - Robust statistical methods are important to the evaluation of toxicological
      interactions (i.e., departures from additivity) among chemicals in a mixture.
      However, different concepts of joint toxic action as applied to the statistical
      analysis of chemical mixture toxicology data or as used in environmental risk
      assessment often appear to conflict with one another. A unifying approach for
      application of statistical methodology in chemical mixture toxicology research is
      based on consideration of change(s) in slope. If the slope of the dose-response
      curve of one chemical does not change in the presence of other chemicals, then
      there is no interaction between the first chemical and the others. Conversely, if
      the rate of change in the response with respect to dose of the first chemical
      changes in the presence of the other chemicals, then an interaction is said to
      exist. This concept of zero interaction is equivalent to the usual approach taken
      in additivity models in the statistical literature. In these additivity models,
      the rate of change in the response as a function of the i(th) chemical does not
      change in the presence of other chemicals in a mixture. It is important to note
      that Berenbaum's (1985, J. Theor. Biol. 114, 413-431) general and fundamental
      definition of additivity does not require the chemicals in the mixture to have a
      common toxic mode of action nor to have similarly shaped dose response curves. We
      show an algebraic equivalence between these statistical additivity models and the
      definition of additivity given by Berenbaum.

PMID- 16081522
TI  - Neurochemical effects of chronic dietary and repeated high-level acute exposure
      to chlorpyrifos in rats.
AB  - Very little is known about the effects of chronic exposure to relatively low
      levels of anticholinesterase insecticides or how the effects of chronic exposure
      compare to those of higher, intermittent exposure. To that end, adult male rats
      were fed an anticholinesterase insecticide, chlorpyrifos (CPF), for 1 year at
      three levels of dietary exposure: 0, 1, or 5 mg/kg/day (0+oil, 1+oil, and 5+oil).
      In addition, half of each of these groups also received a bolus dosage of CPF in
      corn oil ("spiked" animals; 60 mg/kg initially and 45 mg/kg thereafter) every 2
      months (0+CPF, 1+CPF, 5+CPF). Animals were analyzed after 6 or 12 months of
      dosing, and again 3 months after cessation of dosing (i.e., "recovery" animals
      six experimental groups with n = 4-6/group/time point). Cholinesterase (ChE)
      activity was measured in retina, whole blood, plasma, red blood cells, diaphragm,
      and brain [pons, striatum, and the rest of the brain (referred to simply as
      "brain")]. Muscarinic receptor density was assessed in retina, pons, and brain,
      whereas dopamine transporter density and the levels of dopamine and its
      metabolites were assessed in striatum. Cholinesterase activity at 6 and 12 months
      was not different in any of the tissues, indicating that a steady state had been
      reached prior to 6 months. The 1+oil group animals showed ChE inhibition only in
      the blood, whereas the 5+oil group exhibited > or = 50% ChE inhibition in all
      tissues tested. One day after the bolus dose, all three groups (0+CPF, 1+CPF,
      5+CPF) showed > or = 70% ChE inhibition in all tissues. Muscarinic receptor
      density decreased only in the brain of the 5+oil and 5+CPF groups, whereas
      dopamine transporter density increased only at 6 months in all three spiked
      groups. Striatal dopamine or dopamine metabolite levels did not change at any
      time. Three months after CPF dosing ended, all end points had returned to control
      levels. These data indicate that, although chronic feeding with or without
      intermittent spiked dosages with CPF produces substantial biochemical changes in
      a dose- and tissue-related manner, there are no persistent biochemical changes.

PMID- 16081523
TI  - Differential regulation of the lung endothelin system by urban particulate matter
      and ozone.
AB  - Periodic elevation of ambient particulate matter and ozone levels is linked to
      acute cardiac morbidity and mortality. Increased plasma levels of the potent
      vasoconstrictor endothelin (ET)-1, a prognostic indicator of cardiac mortality,
      have been detected in both animal models and humans after exposure to air
      pollutants. The lungs are the primary source of circulating ET-1, but the direct
      effects of individual air pollutants and their interaction in modulating the
      pulmonary endothelin system are unknown. Fischer-344 rats were exposed to
      particles (0, 5, 50 mg/m3 EHC-93), ozone (0, 0.4, 0.8 ppm), or combinations of
      particles and ozone for 4 h. Changes in gene expression were measured using real
      time reverse transcription polymerase chain reaction immediately after exposure
      and following 24 h recovery in clean air. Both pollutants individually increased
      preproET-1, endothelin converting enzyme-1, and endothelial nitric oxide synthase
      mRNA levels in the lungs shortly after exposure, consistent with the concomitant
      increase in plasma of the 21 amino acid ET-1[1-21] peptide measured by HPLC
      fluorescence. PreproET-1 mRNA remained elevated 24 h after exposure to particles
      but not after ozone, in line with previously documented changes of the peptide in
      plasma. Both pollutants transiently increased endothelin-B receptor mRNA
      expression, while ozone decreased endothelin-A receptor mRNA levels. Coexposure
      to particles plus ozone increased lung preproET-1 mRNA but not plasma ET-1[1-21],
      suggesting alternative processing or degradation of endothelins. This coincided
      with an increase in the lungs of matrix metalloproteinase-2 (MMP-2), an enzyme
      that cleaves bigET-1 to ET-1[1-32]. Taken together, our data indicate that ozone
      and particulate matter independently regulate the expression of lung endothelin
      system genes, but show complex toxicological interaction with respect to plasma
      ET-1.

PMID- 16081524
TI  - Gene expression profiling of the PPAR-alpha agonist ciprofibrate in the
      cynomolgus monkey liver.
AB  - Fibrates, such as ciprofibrate, fenofibrate, and clofibrate, are peroxisome
      proliferator-activated receptor-alpha (PPARalpha) agonists that have been in
      clinical use for many decades for treatment of dyslipidemia. When mice and rats
      are given PPARalpha agonists, these drugs cause hepatic peroxisome proliferation,
      hypertrophy, hyperplasia, and eventually hepatocarcinogenesis. Importantly,
      primates are relatively refractory to these effects; however, the mechanisms for
      the species differences are not clearly understood. Cynomolgus monkeys were
      exposed to ciprofibrate at various dose levels for either 4 or 15 days, and the
      liver transcriptional profiles were examined using Affymetrix human GeneChips.
      Strong upregulation of many genes relating to fatty acid metabolism and
      mitochondrial oxidative phosphorylation was observed; this reflects the known
      pharmacology and activity of the fibrates. In addition, (1) many genes related to
      ribosome and proteasome biosynthesis were upregulated, (2) a large number of
      genes downregulated were in the complement and coagulation cascades, (3) a number
      of key regulatory genes, including members of the JUN, MYC, and NFkappaB families
      were downregulated, which appears to be in contrast to the rodent, where JUN and
      MYC are reported to upregulated after PPARalpha agonist treatment, (4) no
      transcriptional signal for DNA damage or oxidative stress was observed, and (5)
      transcriptional signals consistent with an anti-proliferative and a pro-apoptotic
      effect were seen. We also compared the primate data to literature reports of
      hepatic transcriptional profiling in PPARalpha-treated rodents, which showed that
      the magnitude of induction in beta-oxidation pathways was substantially greater
      in the rodent than the primate.

PMID- 16081525
TI  - Probing the control elements of the CYP1A1 switching module in H4IIE hepatoma
      cells.
AB  - Previous research from our laboratory has shown a switch-like response to PCB 126
      mediated CYP1A1 induction in primary rat hepatocytes and in H4IIE rat hepatoma
      cells. On a single cell level, cells appear to be either "on" or "off" for CYP1A1
      induction at a given dose; some cells never respond to PCB 126. These cells
      represent a non-responding population. Cells that are switched "on" by PCB 126
      display varying levels of induction, much like the dimmer on a light switch. The
      goal of the present research is to begin to uncover the mechanism for this switch
      like response to CYP1A1 induction in H4IIE rat hepatoma cells. The AhR pathway is
      modulated by multiple co-activators and by phosphorylation. This research focuses
      on the phosphorylation cascades initiated by PCB 126 and the role they play in
      CYP1A1 induction. Our research reveals a likely role for protein kinase C (PKC)
      in this switch response. Inhibition of PKC by H-7 dramatically reduced the
      percent of cells that express CYP1A1 in response to PCB 126 treatment, as
      determined by flow cytometry. The effect of H-7 was concentration dependent,
      decreasing the number of cells expressing CYP1A1 rather than decreasing the level
      of CYP1A1 in all cells. This finding provides further evidence for the switch
      like behavior of CYP1A1 induction and implicates PKC in this response to PCB126.
      The protein kinase inhibitor, HA-1004, had only a minor effect on CYP1A1
      induction. A high-throughput immunoblot screen for 40 proteins revealed the
      regulation of several proteins/phosphoproteins by PCB 126. Most importantly, two
      proteins containing phosphoserine/phoshothreonine residues were increased by
      PCB126 treatment. However, PKC translocation studies and activity studies failed
      to verify that PCB126 activates PKC. It is possible that constitutive PKC
      activity is sufficient to maintain phosphorylation of critical components of the
      AhR pathway. Immunoblotting studies showed that MAP kinases ERK and JNK are not
      activated by PCB 126 in H4IIE cells and the ERK inhibitor U0126 did not impair
      CYP1A1 induction. Additional studies are planned to further investigate the role
      of PKC in the switch-like response to PCB 126.

PMID- 16081526
TI  - Nucleotides and Mg2+ ions differentially regulate K+ channels and non-selective
      cation channels present in cells forming the stomatal complex.
AB  - Voltage-dependent inward-rectifying (K(in)) and outward-rectifying (K(out)) K(+)
      channels are capable of mediating K(+) fluxes across the plasma membrane.
      Previous studies on guard cells or heterologously expressed K(+) channels
      provided evidence for the requirement of ATP to maintain K(+) channel activity.
      Here, the nucleotide and Mg(2+) dependencies of time-dependent K(in) and K(out)
      channels from maize subsidiary cells were examined, showing that MgATP as well as
      MgADP function as channel activators. In addition to K(out) channels, these
      studies revealed the presence of another outward-rectifying channel type (MgC) in
      the plasma membrane that however gates in a nucleotide-independent manner. MgC
      represents a new channel type distinguished from K(out) channels by fast
      activation kinetics, inhibition by elevated intracellular Mg(2+) concentration,
      permeability for K(+) as well as for Na(+) and insensitivity towards TEA(+).
      Similar observations made for guard cells from Zea mays and Vicia faba suggest a
      conserved regulation of channel-mediated K(+) and Na(+) transport in both cell
      types and species.

PMID- 16081527
TI  - Class III homeodomain leucine-zipper proteins regulate xylem cell
      differentiation.
AB  - Although it has been suggested that class III homeodomain leucine-zipper proteins
      (HD-Zip III) are involved in vascular development, details of the function of
      individual HD-Zip III proteins in vascular differentiation have not been
      resolved. To understand the function of each HD-Zip III protein in vascular
      differentiation precisely, we analyzed the in vitro transcriptional activity and
      in vivo function of Zinnia HD-Zip III genes, ZeHB-10, ZeHB-11 and ZeHB-12, which
      show xylem-related expression. Transgenic Arabidopsis plants harboring
      cauliflower mosaic virus 35S-driven ZeHB-10 and ZeHB-12 with a mutation in the
      START domain (mtZeHB-10, mtZeHB-12) showed a higher production of tracheary
      elements (TEs) and xylem precursor cells, respectively. A systematic analysis
      with Genechip arrays revealed that overexpression of mtZeHB-12 rapidly induced
      various genes, including brassinosteroid-signaling pathway-related genes and
      genes for transcription factors that are expressed specifically in vascular
      tissues in situ. Furthermore, mtZeHB-12 overexpression did not induce TE-specific
      genes, including genes related to programmed cell death and lignin
      polymerization, but did induce lignin monomer synthesis-related genes, which are
      expressed in xylem parenchyma cells. These results suggest that ZeHB-12 is
      involved in the differentiation of xylem parenchyma cells, but not of TEs.

PMID- 16081528
TI  - The 14-3-3 gene expression specificity in response to stress is promoter
      dependent.
AB  - Genomic clone coding for the 16R isoform of 14-3-3 proteins from potato plants
      has recently been described. This paper reports on 20R-gene isolation and
      analysis, and compares two isoforms. The northern blot analysis of mRNA of the
      20R 14-3-3 isoform suggests its similarity to 16R. Vascular tissue-specific
      expression and age-dependent synthesis in potato leaves has been detected in both
      promoters. Screening of the potato genomic library using 20R cDNA isoform
      resulted in identification and isolation of the corresponding gene. This gene
      contains four exons and three introns. Inspecting the promoter sequence of the
      20R isoform revealed several boxes important for the regulation of gene
      expression. The strongest GUS expression in transgenic potato plants transformed
      with the uidA reporter gene under the 20R promoter has been found in young leaf
      and stem vascular tissue, root tips, pollen and ovules. Mature fragments exhibit
      a significant decrease in GUS staining, which suggests age-dependent promoter
      activity. The analysis of transgenic plants transformed with 20R-GUS in contrast
      to 16R-GUS has revealed strong activation of the 20R promoter by metal ions and
      NaCl. Instead the 16R promoter is strongly affected by virus and salicylic acid
      treatments. The only factor, which strongly induced both promoters, was abscisic
      acid. It is thus suggested that promoter domain composition is the main factor
      differentiating the appearance of 14-3-3 isoforms.

PMID- 16081529
TI  - Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus
      entry.
AB  - Severe acute respiratory syndrome (SARS) is caused by an emergent coronavirus
      (SARS-CoV), for which there is currently no effective treatment. SARS-CoV
      mediates receptor binding and entry by its spike (S) glycoprotein, and infection
      is sensitive to lysosomotropic agents that perturb endosomal pH. We demonstrate
      here that the lysosomotropic-agent-mediated block to SARS-CoV infection is
      overcome by protease treatment of target-cell-associated virus. In addition, SARS
      CoV infection was blocked by specific inhibitors of the pH-sensitive endosomal
      protease cathepsin L. A cell-free membrane-fusion system demonstrates that
      engagement of receptor followed by proteolysis is required for SARS-CoV membrane
      fusion and indicates that cathepsin L is sufficient to activate membrane fusion
      by SARS-CoV S. These results suggest that SARS-CoV infection results from a
      unique, three-step process: receptor binding and induced conformational changes
      in S glycoprotein followed by cathepsin L proteolysis within endosomes. The
      requirement for cathepsin L proteolysis identifies a previously uncharacterized
      class of inhibitor for SARS-CoV infection.

PMID- 16081530
TI  - Arabidopsis ARGONAUTE1 is an RNA Slicer that selectively recruits microRNAs and
      short interfering RNAs.
AB  - ARGONAUTE (AGO) RNA-binding proteins are involved in RNA silencing. They bind to
      short interfering RNAs (siRNAs) and microRNAs (miRNAs) through a conserved PAZ
      domain, and, in animals, they assemble into a multisubunit RNA-induced silencing
      complex (RISC). The mammalian AGO2, termed Slicer, directs siRNA- and miRNA
      mediated cleavage of a target RNA. In Arabidopsis, there are 10 members of the
      AGO family, and the AGO1 protein is potentially the Slicer component in different
      RNA-silencing pathways. Here, we show that AGO1 selectively recruits certain
      classes of short silencing-related RNA. AGO1 is physically associated with
      miRNAs, transacting siRNAs, and transgene-derived siRNAs but excludes virus
      derived siRNAs and 24-nt siRNAs involved in chromatin silencing. We also show
      that AGO1 has Slicer activity. It mediates the in vitro cleavage of a mir165
      target RNA in a manner that depends on the sequence identity of amino acid
      residues in the PIWI domain that are predicted by homology with animal Slicer
      competent AGO proteins to constitute the RNase catalytic center. However, unlike
      animals, we find no evidence that AGO1 Slicer is in a high molecular weight RNA
      induced silencing complex. The Slicer activity fractionates as a complex of
      approximately 150 kDa that likely constitutes the AGO1 protein and associated RNA
      without any other proteins. Based on sequence similarity, we predict that other
      Arabidopsis AGOs might have a similar catalytic activity but recruit different
      subsets of siRNAs or miRNAs.

PMID- 16081531
TI  - Protein-folding landscapes in multichain systems.
AB  - Computational studies of proteins have significantly improved our understanding
      of protein folding. These studies are normally carried out by using chains in
      isolation. However, in many systems of practical interest, proteins fold in the
      presence of other molecules. To obtain insight into folding in such situations,
      we compare the thermodynamics of folding for a Miyazawa-Jernigan model 64-mer in
      isolation to results obtained in the presence of additional chains. The melting
      temperature falls as the chain concentration increases. In multichain systems,
      free-energy landscapes for folding show an increased preference for misfolded
      states. Misfolding is accompanied by an increase in interprotein interactions;
      however, near the folding temperature, the transition from folded chains to
      misfolded and associated chains is entropically driven. A majority of the most
      probable interprotein contacts are also native contacts, suggesting that native
      topology plays a role in early stages of aggregation.

PMID- 16081532
TI  - Diverse DNA transposons in rotifers of the class Bdelloidea.
AB  - We surveyed the diversity, structural organization, and patterns of evolution of
      DNA transposons in rotifers of the class Bdelloidea, a group of basal triploblast
      animals that appears to have evolved for millions of years without sexual
      reproduction. Representatives of five superfamilies were identified: ITm
      (IS630/Tc/mariner), hAT, piggyBac, helitron, and foldback. Except for mariners,
      no fully intact copies were found. Mariners, both intact and decayed, are present
      in high copy number, and those described here may be grouped in several closely
      related lineages. Comparisons across lineages show strong evidence of purifying
      selection, whereas there is little or no evidence of such selection within
      lineages. This pattern could have resulted from repeated horizontal transfers
      from an exogenous source, followed by limited intragenomic proliferation, or,
      less plausibly, from within-host formation of new lineages under host- or element
      based selection for function, in either case followed by eventual inactivation
      and decay. Unexpectedly, the flanking sequences surrounding the majority of
      mariners are very similar, indicating either insertion specificity or
      proliferation as part of larger DNA segments. Members of all superfamilies are
      present near chromosome ends, associated with the apparently domesticated
      retroelement Athena, in large clusters composed of diverse DNA transposons, often
      inserted into each other, whereas the examined gene-rich regions are nearly
      transposon-free.

PMID- 16081533
TI  - Polarizable molecules in the vibrational spectroscopy of water.
AB  - We examine the role of electronic polarizability in water on short (tens of
      femtoseconds), intermediate (hundreds of femtoseconds), and long (approximately 1
      ps) time scales by comparing molecular dynamics results to experimental data for
      vibrational spectroscopy of HOD in liquid D2O. Because the OH absorption
      frequency is sensitive to the details of the atomic forces experienced in the
      liquid, our results provide important quantitative comparisons for several
      popular empirical water potentials. When compared with their fixed-charge
      counterparts, the polarizable models give similar slower long time constants for
      the decay of vibrational correlations and re-orientational motion that is in
      better agreement with experiments. Polarizable potentials yield qualitatively
      dissimilar predictions for frequency fluctuations and transition dipole moment
      fluctuations at equilibrium. Models that confine the polarizability to the plane
      of the molecule (i.e., TIP4P-FQ) overestimate the width of the distribution
      describing frequency fluctuations by more than a factor of two. These models also
      underestimate the amplitude of the hydrogen-bond stretch at 170 cm(-1). A
      potential that has both an out-of-plane polarization and fluctuating charges,
      POL5-TZ, compares best with experiments. We interpret our findings in terms of
      microscopic dynamics and make suggestions that may improve the quality of
      emerging polarizable force fields for water.

PMID- 16081534
TI  - Identifying gene-independent noncoding functional elements in the yeast ribosomal
      DNA by phylogenetic footprinting.
AB  - Sequences involved in the regulation of genetic and genomic processes are
      primarily located in noncoding regions. Identifying such cis-acting sequences
      from sequence data is difficult because their patterns are not readily apparent,
      and, to date, identification has concentrated on regions associated with gene
      coding functions. Here, we used phylogenetic footprinting to look for gene
      independent noncoding elements in the ribosomal RNA gene repeats from several
      Saccharomyces species. Similarity plots of ribosomal intergenic spacer alignments
      from six closely related Saccharomyces species allowed the identification of
      previously characterized functional elements, such as the origin-of-replication
      and replication-fork barrier sites, demonstrating that this method is a powerful
      predictor of noncoding functional elements. Seventeen previously uncharacterized
      elements, showing high levels of conservation, were also discovered. The
      conservation of these elements suggests that they are functional, and we
      demonstrate the functionality of two classes of these elements, a putative
      bidirectional noncoding promoter and a series of conserved peaks with matches to
      the origin-of-replication core consensus. Our results paint a comprehensive
      picture of the functionality of the Saccharomyces ribosomal intergenic region and
      demonstrate that functional elements not involved in gene-coding function can be
      identified by using comparative genomics based on sequence conservation.

PMID- 16081535
TI  - Advanced glycation endproduct-induced aging of the retinal pigment epithelium and
      choroid: a comprehensive transcriptional response.
AB  - Advanced glycation endproduct (AGE) formation is a trigger for the onset of age
      related disease. To evaluate AGE-induced change in the ocular fundus, 5-mo-old
      C57BL/6 mice were given low-dose D-galactose (D-gal) for 8 wk and evaluated by
      AGE fluorescence, electroretinography (ERG), electron microscopy, and microarray
      analysis for 20 wk. Although AGE fluorescence was increased in D-gal-treated
      retinal pigment epithelium (RPE)-choroid compared with controls at all time
      points, ERG showed no AGE-induced functional toxicity. Progressive
      ultrastructural aging in the RPE-choroid was associated temporally with a
      transcriptional response of early inflammation, matrix expansion, and aberrant
      lipid processing and, later, down-regulation of energy metabolism genes, up
      regulation of crystallin genes, and altered expression of cell structure genes.
      The overall transcriptome is similar to the generalized aging response of
      unrelated cell types. A subset of transcriptional changes is similar to early
      atherosclerosis, a chronic inflammatory disease characterized by matrix expansion
      and lipid deposition. These changes suggest an important contribution of a single
      environmental stimulus to the complex aging response.

PMID- 16081536
TI  - Activation of the plant plasma membrane H+-ATPase by phosphorylation and binding
      of 14-3-3 proteins converts a dimer into a hexamer.
AB  - Plant plasma membrane H+-ATPases (PMAs) can be activated by phosphorylation of
      their penultimate residue (a Thr) and the subsequent binding of regulatory 14-3-3
      proteins. Although 14-3-3 proteins usually exist as dimers and can bind two
      targets, the in vivo effects of their binding on the quaternary structure of H+
      ATPases have never been examined. To address this question, we used a Nicotiana
      tabacum cell line expressing the Nicotiana plumbaginifolia PMA2 isoform with a 6
      His tag. The purified PMA2 was mainly nonphosphorylated and 14-3-3-free, and it
      was shown by blue native gel electrophoresis and chemical cross-linking to exist
      as a dimer. Fusicoccin treatment of the cells resulted in a dramatic increase in
      Thr phosphorylation, 14-3-3 binding, and in vivo and in vitro ATPase activity, as
      well as in the conversion of the dimer into a larger, possibly hexameric,
      complex. PMA2 phosphorylation and 14-3-3 binding were observed also when cells in
      stationary growth phase were metabolically activated by transfer to fresh medium.
      When expressed in yeast, PMA2 was also phosphorylated and formed a complex with
      14-3-3 proteins without requiring fusicoccin; no complex was observed when
      phosphorylation was prevented by mutagenesis. Single-particle analysis by
      cryoelectron microscopy showed that the PMA2-14-3-3 complex is a wheel-like
      structure with a 6-fold symmetry, suggesting that the activated complex consists
      of six H+-ATPase molecules and six 14-3-3 molecules.

PMID- 16081537
TI  - NF-Ya activates multiple hematopoietic stem cell (HSC) regulatory genes and
      promotes HSC self-renewal.
AB  - Hematopoietic stem cell (HSC) self-renewal and differentiation are influenced
      through multiple pathways, including homeobox transcription factors, signaling
      through beta-catenin and Notch-1, telomerase, and p27. How these multiple
      pathways interact and are orchestrated is currently unknown. We now report that
      NF-Ya, the regulatory and DNA-binding subunit of the trimeric transcription
      factor NF-Y, plays a central, integrating role in several of these HSC pathways.
      NF-Ya is preferentially expressed in HSC-enriched bone marrow subpopulations, and
      NF-Ya mRNA rapidly declines with HSC differentiation. Overexpression of NF-Ya in
      primitive hematopoietic cells activates the transcription of multiple HOX4
      paralogs, as well as Notch-1, LEF-1, and telomerase RNA. HSCs overexpressing NF
      Ya are biased toward primitive hematopoiesis in vitro and show strikingly
      increased in vivo repopulating abilities after single or sequential bone marrow
      transplantation. Thus, NF-Ya is a potent cellular regulator of HSC self-renewal.

PMID- 16081538
TI  - Geographic routing in social networks.
AB  - We live in a "small world," where two arbitrary people are likely connected by a
      short chain of intermediate friends. With scant information about a target
      individual, people can successively forward a message along such a chain.
      Experimental studies have verified this property in real social networks, and
      theoretical models have been advanced to explain it. However, existing
      theoretical models have not been shown to capture behavior in real-world social
      networks. Here, we introduce a richer model relating geography and social-network
      friendship, in which the probability of befriending a particular person is
      inversely proportional to the number of closer people. In a large social network,
      we show that one-third of the friendships are independent of geography and the
      remainder exhibit the proposed relationship. Further, we prove analytically that
      short chains can be discovered in every network exhibiting the relationship.

PMID- 16081539
TI  - Interferon-alpha and -beta differentially regulate osteoclastogenesis: role of
      differential induction of chemokine CXCL11 expression.
AB  - In humans, type I interferon (IFN) is a family of 17 cytokines, among which the
      alpha subtypes and the beta subtype are differentially expressed. It has been
      suggested that IFN-beta activates a specific signaling cascade in addition to
      those activated by all type I IFNs. Nevertheless, no true biological relevance
      for a differential activity of alpha and beta IFN subtypes has been identified so
      far. Because type I IFNs are critical for the regulation of osteoclastogenesis in
      mice, we have compared the effect of IFN-alpha2 and IFN-beta on the
      differentiation of human monocytes into osteoclasts. Primary monocytes undergoing
      osteoclastic differentiation are highly and equally sensitive to both alpha2 and
      beta IFNs as determined by measuring the induction levels of several IFN
      stimulated genes. However, IFN-beta was 100-fold more potent than the alpha2
      subtype at inhibiting osteoclastogenesis. Expression profiling of the genes
      differentially regulated by IFN-alpha2 and IFN-beta in this cellular system
      revealed the chemokine CXCL11 as the only IFN-induced gene differentially up
      regulated by IFN-beta. We show that recombinant CXCL11 by itself inhibits
      osteoclastic differentiation. These results indicate that autocrine-acting CXCL11
      mediates, at least in part, the regulations of osteoclastogenesis by type I IFNs.

PMID- 16081540
TI  - Hyperphosphorylation regulates the activity of SREBP1 during mitosis.
AB  - The sterol regulatory element-binding protein (SREBP) family of transcription
      factors controls the biosynthesis of cholesterol and other lipids, and lipid
      synthesis is critical for cell growth and proliferation. We were, therefore,
      interested in the expression and activity of SREBPs during the cell cycle. We
      found that the expression of a number of SREBP-responsive promoter-reporter genes
      were induced in a SREBP-dependent manner in cells arrested in G2/M. In addition,
      the mature forms of SREBP1a and SREBP1c were hyperphosphorylated in mitotic
      cells, giving rise to a phosphoepitope recognized by the mitotic protein
      monoclonal-2 (MPM-2) antibody. In contrast, SREBP2 was not hyperphosphorylated in
      mitotic cells and was not recognized by the MPM-2 antibody. The MPM-2 epitope was
      mapped to the C terminus of mature SREBP1, and the mitosis-specific
      hyperphosphorylation of SREBP1 depended on this domain of the protein. The
      transcriptional and DNA-binding activity of SREBP1 was enhanced in cells arrested
      in G2/M, and these effects depended on the C-terminal domain of the protein. In
      part, these effects could be explained by our observation that mature SREBP1 was
      stabilized in G2/M. In agreement with these observations, we found that the
      synthesis of cholesterol was increased in G2/M-arrested cells. Thus, our results
      demonstrate that the activity of mature SREBP1 is regulated by phosphorylation
      during the cell cycle, suggesting that SREBP1 may provide a link between lipid
      synthesis, proliferation, and cell growth.

PMID- 16081541
TI  - Genetic reprogramming of tumor cells by zinc finger transcription factors.
AB  - Cancer arises by the accumulation of genetic alterations in DNA leading to
      aberrant gene transcription. Expression-profiling studies have correlated
      genomewide expression signatures with malignancy. However, functional analysis
      elucidating the contribution and synergy of genes in specific cancer cell
      phenotypes remains a formidable obstacle. Herein, we describe an alternative
      genetic approach for identification of genes involved in tumor progression by
      using a library of zinc finger artificial transcription factors (ATFs) and
      functional screening of tumor cells as a source of genetic plasticity and clonal
      selection. We isolated a six-zinc finger transcriptional activator (TF 20-VP, TF
      20 containing the VP64 activator domain) that acts to reprogram a drug-sensitive,
      poorly invasive, and nonmetastatic cell line into a cell line with a drug
      resistant, highly invasive, and metastatic phenotype. Differential expression
      profiles of cells expressing TF 20-VP followed by functional studies, both in
      vitro and in animal models, revealed that invasion and metastasis requires co
      regulation of multiple target genes. Significantly, the E48 antigen, associated
      with poor metastasis-free survival in head and neck cancer, was identified as one
      specific target of TF 20-VP. We have shown phenotypic modulation of tumor cell
      behavior by E48 expression, including enhanced cell migration in vitro and tumor
      cell dissemination in vivo. This study demonstrates the use of ATFs to identify
      the group of genes that cooperate during tumor progression. By co-regulating
      multiple targets, ATFs can be used as master genetic switches to reprogram and
      modulate complex neoplastic phenotypes.

PMID- 16081542
TI  - A priori prediction of adsorption isotherm parameters and chromatographic
      behavior in ion-exchange systems.
AB  - The a priori prediction of protein adsorption behavior has been a long-standing
      goal in several fields. In the present work, property-modeling techniques have
      been used for the prediction of protein adsorption thermodynamics in ion-exchange
      systems directly from crystal structure. Quantitative structure-property
      relationship models of protein isotherm parameters and Gibbs free energy changes
      in ion-exchange systems were generated by using a support vector machine
      regression technique. The predictive ability of the models was demonstrated for
      two test-set proteins not included in the model training set. Molecular
      descriptors selected during model generation were examined to gain insights into
      the important physicochemical factors influencing stoichiometry, equilibrium,
      steric effects, and binding affinity in protein ion-exchange systems. The a
      priori prediction of protein isotherm parameters can have direct implications for
      various ion-exchange processes. As proof of concept, a multiscale modeling
      approach was used for predicting the chromatographic separation of a test set of
      proteins using the isotherm parameters obtained from the quantitative structure
      property relationship models. The simulated column separation showed good
      agreement with the experimental data. The ability to predict chromatographic
      behavior of proteins directly from their crystal structures may have significant
      implications for a range of biotechnology processes.

PMID- 16081543
TI  - Bovine papillomavirus E7 transformation function correlates with cellular p600
      protein binding.
AB  - The E7 oncoprotein of bovine papillomavirus type 1 (BPV-1) is required for the
      full transformation activity of the virus. However, the mechanism by which E7
      contributes to cellular transformation is unknown. To address this question, we
      used the proteomic approach of tandem affinity purification to identify cellular
      proteins that are in complex with E7, and identified the 600-kDa protein, p600,
      as a binding partner of E7. The ability of E7 to complex with p600 correlated
      with its ability to enhance anchorage independence of BPV-1 E6-expressing cells.
      Furthermore, E7 mutant proteins impaired in their ability to bind p600 were
      transformation defective. Additionally, knockdown of p600 reduced transformation
      of cells expressing both BPV-1 E6 and E7, as well as E6 alone, suggesting that
      the ability of E7 to transformed cells is mediated, at least in part, through its
      ability to bind p600. These data complement work that shows that HPV16 E7 also
      interacts with p600, and that this interaction correlates with the ability of
      HPV16 E7 to transform cells. These studies thus identify p600 as a shared target
      of the E7 proteins of multiple papillomaviruses.

PMID- 16081544
TI  - Tailored education may reduce health literacy disparities in asthma self
      management.
AB  - RATIONALE: Although inadequate health literacy has been associated with lower
      asthma medication knowledge and worse metered-dose inhaler (MDI) technique, the
      relationship between health literacy and the capacity to learn asthma self
      management skills is unknown. OBJECTIVES: In this prospective cohort study of
      adults hospitalized for severe asthma exacerbations at two inner-city hospitals,
      we examined the relationship between inadequate health literacy and difficulties
      learning and retaining instructions about discharge medications and appropriate
      MDI technique. METHODS: At hospital discharge, participants received one-on-one,
      30-min, guideline-based, written and oral instruction about their asthma
      discharge regimen as well as appropriate MDI technique. MEASUREMENTS AND MAIN
      RESULTS: Seventy-three patients were enrolled. Inadequate health literacy was
      identified in 16 (22%) participants. Before instruction, inadequate health
      literacy was associated with lower asthma medication knowledge (5.2/10 vs.
      7.2/10, p < 0.001) and worse MDI technique (3.2/6 vs. 3.9/6, p = 0.03). However,
      inadequate health literacy was not associated with difficulty learning (p = 0.33)
      or retaining (p = 0.35) instructions about the discharge regimen. Similarly,
      inadequate health literacy was not associated with difficulty learning (p = 0.26)
      or retaining (p = 0.97) appropriate MDI technique. Results were similar in
      multivariable models adjusted for demographic characteristics and asthma severity
      indicators. CONCLUSIONS: These findings suggest that inadequate health literacy
      is a surmountable barrier to learning and remembering key asthma self-management
      skills.

PMID- 16081545
TI  - Enzyme-linked immunospot and tuberculin skin testing to detect latent
      tuberculosis infection.
AB  - RATIONALE: Diagnosis of latent tuberculosis infection (LTBI) is currently based
      on the tuberculin skin test. The enzyme-linked immunospot assay (ELISPOT) is a
      new blood test to diagnose LTBI. OBJECTIVE: To compare the ELISPOT and the
      tuberculin skin test for detecting LTBI in contacts of patients with
      tuberculosis. METHODS: Prospective study of 413 contacts of patients with
      tuberculosis. MEASUREMENTS AND MAIN RESULTS: Because there is no gold standard
      for LTBI, the sensitivity and specificity of the ELISPOT and tuberculin skin test
      cannot be directly measured. For each contact, we therefore estimated the
      likelihood of having LTBI by calculating a contact score that quantified exposure
      to and infectiousness of the index case. We analyzed the relationship of contact
      score to ELISPOT and tuberculin skin test results. The likelihood of a positive
      ELISPOT (p = 0.0005) and a tuberculin skin test (p = 0.01) increased
      significantly with rising contact scores. The contact score was more strongly
      related to the ELISPOT than to the tuberculin skin test results, although this
      difference was not statistically significant. Among U.S.-born persons and those
      who were not vaccinated with bacille Calmette-Guerin, approximately 30% had
      positive ELISPOT or tuberculin skin test results. Foreign-born, bacille Calmette
      Guerin-vaccinated persons were significantly more likely to have a positive
      tuberculin skin test than a positive ELISPOT result (p < 0.0001). CONCLUSIONS:
      Compared with the tuberculin skin test, the ELISPOT appears to be at least as
      sensitive for diagnosis of LTBI in contacts of patients with tuberculosis.

PMID- 16081546
TI  - Lung-marginated monocytes modulate pulmonary microvascular injury during early
      endotoxemia.
AB  - RATIONALE: The role of monocytes in acute endotoxemia has been ascribed to
      systemic release of mediators within the central circulation. Little is known
      about the potential role of "marginated" monocytes in regulating microvascular
      inflammatory signaling. OBJECTIVES: To investigate whether lung-marginated
      monocytes can locally activate pulmonary endothelial cells through cell contact
      dependent interactions in early endotoxemia. METHODS: Mice were challenged with
      LPS to produce acute endotoxemia and pulmonary vascular injury. Adoptive transfer
      of ex vivo LPS-stimulated donor leukocytes to recipient mice was also performed
      to evaluate cell-associated inflammatory signaling between monocytes and
      endothelial cells within the lung. Cell suspensions from excised lungs were
      analyzed by flow cytometry for expression of tumor necrosis factor alpha (TNF
      alpha) on monocytes and cell adhesion molecules on endothelial cells. RESULTS:
      Substantial numbers of monocytes rapidly marginated to the lungs after endotoxin
      challenge in mice, and lung-marginated monocytes expressed significantly higher
      levels of membrane TNF than circulating monocytes, due to higher TNF production
      by the marginated cells. Injection of activated wild-type donor leukocytes to
      wild-type or TNF receptor double knockout recipients demonstrated that lung
      marginated monocytes can induce TNF-dependent upregulation of adhesion molecules
      on pulmonary endothelial cells. Injection of activated donor leukocytes from TNF
      knock-in mice that express uncleavable mutant membrane TNF also induced adhesion
      molecule upregulation in wild-type recipients without a systemic soluble TNF
      release. CONCLUSIONS: These results reveal a previously unacknowledged role for
      lung-marginated monocytes in early endotoxemia, exerting local, cell-associated
      TNF signaling within the pulmonary microcirculation, contributing to the
      evolution of pulmonary vascular injury.

PMID- 16081548
TI  - Physiologic effects of noninvasive ventilation during acute lung injury.
AB  - A prospective, crossover, physiologic study was performed in 10 patients with
      acute lung injury to assess the respective short-term effects of noninvasive
      pressure-support ventilation and continuous positive airway pressure. We measured
      breathing pattern, neuromuscular drive, inspiratory muscle effort, arterial blood
      gases, and dyspnea while breathing with minimal support and the equipment for
      measurements, with two combinations of pressure-support ventilation above
      positive end-expiratory pressure (10-10 and 15-5 cm H2O), and with continuous
      positive airway pressure (10 cm H2O). Tidal volume was increased with pressure
      support, and not with continuous positive airway pressure. Neuromuscular drive
      and inspiratory muscle effort were lower with the two pressure-support
      ventilation levels than with other situations (p < 0.05). Dyspnea relief was
      significantly better with high-level pressure-support ventilation (15-5 cm H2O; p
      < 0.001). Oxygenation improved when 10 cm H2O positive end-expiratory pressure
      was applied, alone or in combination. We conclude that, in patients with acute
      lung injury (1) noninvasive pressure-support ventilation combined with positive
      end-expiratory pressure is needed to reduce inspiratory muscle effort; (2)
      continuous positive airway pressure, in this setting, improves oxygenation but
      fails to unload the respiratory muscles; and (3) pressure-support levels of 10
      and 15 cm H2O provide similar unloading but differ in their effects on dyspnea.

PMID- 16081547
TI  - Tidal volume reduction in patients with acute lung injury when plateau pressures
      are not high.
AB  - Use of a volume- and pressure-limited mechanical ventilation strategy improves
      clinical outcomes of patients with acute lung injury and acute respiratory
      distress syndrome (ALI/ARDS). However, the extent to which tidal volumes and
      inspiratory airway pressures should be reduced to optimize clinical outcomes is a
      controversial topic. This article addresses the question, "Is there a safe upper
      limit to inspiratory plateau pressure in patients with ALI/ARDS?" We reviewed
      data from animal models with and without preexisting lung injury, studies of
      normal human respiratory system mechanics, and the results of five clinical
      trials of lung-protective mechanical ventilation strategies. We also present an
      original analysis of data from the largest of the five clinical trials. The
      available data from each of these assessments do not support the commonly held
      view that inspiratory plateau pressures of 30 to 35 cm H2O are safe. We could not
      identify a safe upper limit for plateau pressures in patients with ALI/ARDS.

PMID- 16081549
TI  - Is interleukin-10 a "10" in virus-provoked asthma?

PMID- 16081550
TI  - Asthma may be more severe if it is work-related.

PMID- 16081551
TI  - Inhaled corticosteroids and chronic obstructive pulmonary disease: new and
      improved evidence?

PMID- 16081552
TI  - Role of high-resolution computed tomography in idiopathic pulmonary fibrosis: the
      final word?

PMID- 16081553
TI  - Daily inhaled corticosteroid treatment should be prescribed for mild persistent
      asthma. Pro.

PMID- 16081554
TI  - Daily inhaled corticosteroid treatment should not be prescribed for mild
      persistent asthma. Con.

PMID- 16081559
TI  - The role of four months of rifampicin in the treatment of latent tuberculosis
      infection.

PMID- 16081561
TI  - Melatonin for patients with asthma: safety and efficacy are still dubious.

PMID- 16081563
TI  - Bradykinin and tachykinin-induced leukotriene release in airway virus infections.

PMID- 16081564
TI  - Acute purulent sinusitis triggered by topical nasal nitric oxide synthase
      inhibition.

PMID- 16081565
TI  - A brief history and current status of a dental therapy initiative in the United
      States.

PMID- 16081566
TI  - Predental and dental students serve the community and learn about preventive
      dentistry.

PMID- 16081567
TI  - Strategies for making research more accessible to dental students.
AB  - Increasing student involvement in research has potential rewards for both faculty
      and students. Both groups have demands on their time, interest, and commitment
      that frequently result in low student research activity. Dental schools can make
      research more accessible to students by increasing student understanding of the
      importance of research, establishing rotating research positions, providing
      compensation, pursuing projects that interest students, and providing time in the
      curriculum for research by restructuring the basic sciences curriculum during the
      first two years of dental school. No attempt to make the research process easier
      or more accessible should compromise the integrity of the scientific process, but
      increasing students' research involvement will pay long-term dividends for dental
      schools and the profession.

PMID- 16081568
TI  - Relationship between performance in dental school and performance on a dental
      licensure examination: an eight-year study.
AB  - This study assessed relationships between academic performance in dental school
      and "first attempt" performance on a state dental licensure examination for 1996
      2003 graduates from the University of Florida College of Dentistry (UFCD). The
      524 graduates were ranked into quartiles based on graduating GPA. Using analysis
      of variance (ANOVA), the students' mean exam score (or exam section score) for
      each respective quartile (n=131) was compared with mean score for graduates in
      the combined four quartiles (n=524). ANOVA assessments, by quartile, were
      performed for the following six measures: 1) overall composite score on the
      dental licensure exam, 2) clinical periodontics section, 3) clinical amalgam
      section, 4) combination of clinical periodontics and clinical amalgam, 5)
      laboratory (manikin exam) with a written prosthodontic exam, and 6) manikin exam
      without the prosthodontic exam. For the overall exam and all exam sections, a
      significant (p<0.001) relationship was found between higher mean exam scores and
      academic ranking in quartile 1. A significant relationship was found between
      performance (lower mean scores) and ranking in quartile 4 for all exam sections,
      with the exception of the clinical periodontal section. The results of this study
      indicate a correlation between performance in dental school and performance on
      the Florida dental licensure exam for 1996-2003 UFCD graduates.

PMID- 16081569
TI  - A model for clinical credentialing of dental school faculty.
AB  - Committed to the premise that the same standards of review for clinical practice
      may be applied to clinical teaching, The University of Texas Health Science
      Center Dental Branch at Houston began credentialing clinical faculty in 1997 as
      part of its quality assurance and risk management program, one of the first
      dental schools in the country to do so. Credentialing, modeled after health care
      institutions such as hospitals, is general and procedure-specific involving the
      review of qualifications such as licensure, training, education, experience, and
      performance of professional practitioners; measuring those qualifications against
      pre-established criteria; and granting of "clinical privileges" to clinical
      faculty to perform or supervise procedures for which they are deemed qualified,
      based on that review. The development process included the leadership of the
      Quality Assurance and Risk Management Committee who met with all interested
      parties, explained the rationale and justification for credentialing, and
      successfully gained the support of the clinical department chairs, clinical
      faculty, faculty senate, and the administration of the school in implementing the
      credentials process. Evaluation of this process indicates that it has been useful
      in providing a mechanism to address a variety of patient care and clinical
      education issues such as faculty competency, compliance, and accommodations
      through a peer review process.

PMID- 16081570
TI  - A survey of Canadian dental hygiene faculty needs and credentials.
AB  - The American Dental Education Association recently reported that the growing
      shortage of qualified faculty in dental hygiene education programs has reached a
      crisis situation. The authors hypothesized that Canadian dental hygiene programs
      will face a similar shortage. However, a review of the literature identified no
      studies that investigated Canadian dental hygiene faculty shortages. To address
      this gap in knowledge, a twenty-three-item descriptive survey and cover letter
      were mailed to the director of each Canadian school of dental hygiene (N=31) in
      spring 2003. The survey and letter were translated into French for francophone
      (French-speaking) schools. Follow-up telephone calls were made to nonrespondent
      programs. Survey results were analyzed using descriptive statistical methods. The
      response rate was 84 percent. Results revealed that 20 percent of schools had
      sought to fill empty faculty positions within the year and 47 percent of full
      time faculty were forty-nine years or older. Within the next two years, 24
      percent of dental hygiene programs in Canada will have full-time faculty
      positions available, growing to 40 percent within the next five years.
      Respondents indicated that they preferred faculty to hold a credential above the
      diploma whether teaching full-time (92 percent) or part-time (88 percent). Other
      required qualifications included previous teaching experience, current clinical
      experience, and eligibility for licensure in the province for teaching in
      Canadian dental hygiene programs.

PMID- 16081571
TI  - Predental enrichment activities of U.S. colleges and universities.
AB  - The purpose of this study was to examine predental enrichment activities and
      their impact on the number of applicants from some of the nation's top dental
      school feeder institutions (DSFI). The DSFI were identified by their total number
      of applicants to dental schools and the number of applicants per total student
      enrollment. A survey consisting of twenty-seven questions on possible predental
      enrichment activities was administered by phone or sent by email to eighty-eight
      DSFI, with forty-nine responding. In addition to identifying and characterizing
      the most common predental enrichment activities, the relationships among the
      number of applicants, predental activities, and total student enrollments per
      institution were evaluated. The total number of dental school
      applicants/institution was correlated with the total student
      enrollment/institution (r=0.529) and the number of predental
      activities/institution (r=0.520). No correlation was observed between the number
      of activities at an institution and dental school applicants per thousand
      enrolled. Sixteen of the DSFI reported ten or more enrichment activities, the
      most common being preprofessional health advising (96 percent), dentistry club
      (88 percent), and volunteer programs (73 percent). In general, larger
      institutions produced more applicants and provided more enrichment activities.
      However, there was no correlation between the number of dental school applicants
      per thousand students enrolled and the number of activities at an institution.
      Results indicate that there are specific predental enrichment activities common
      to some of the top dental school feeder institutions in the United States. A
      better understanding of successful feeder programs may assist nonfeeder schools
      in developing or strengthening an interest in dentistry as a career option.

PMID- 16081572
TI  - Attitudes of advanced dental education students toward individuals with AIDS.
AB  - The number of patients with HIV/AIDS who receive dental care is increasing. This
      study was undertaken to gain a better understanding of the attitudes of dentists
      enrolled in postgraduate training toward AIDS and homosexuals. Each respondent
      received a 500-word patient case vignette and two scales for recording
      impressions of the person described in the vignette. There were four vignettes,
      identical except that the portrayed individual's illness was identified as either
      AIDS or leukemia and sexual preference as either homosexual or heterosexual. Two
      way analyses of variance and t tests (p<.05) revealed a bias toward individuals
      with AIDS and toward homosexuals. Respondents reacted more negatively to both
      groups on the Social Interaction Scale as seen in total scale scores as well as
      to individual scale items. In addition, although overall Prejudicial Evaluation
      Scale scores displayed no evidence of bias, several individual scale items did.
      It is important to ensure that dentists' attitudes toward patients with AIDS and
      homosexuals are not a barrier to these patients receiving the best possible care.
      Therefore, dental education programs at all levels should give consideration to
      interventions to address provider attitudes and potential biases.

PMID- 16081573
TI  - Promotion of tobacco cessation through dental hygiene education: a pilot study.
AB  - The purposes of this pilot study were as follows: 1) to determine the percentage
      and frequency of dental hygiene graduates who were providing tobacco cessation
      counseling (TCC) activities, after receiving TCC training during their formative
      years of education; 2) to identify the graduates' stages of change using the
      transtheoretical model regarding TCC; and 3) to identify factors influencing the
      delivery of TCC. A convenience sample of fifty-one Minnesota State University,
      Mankato (MSU) dental hygiene graduates were surveyed in this study. Wilcoxen
      signed rank tests were used to analyze the relationship between counseling
      actions and dental hygienists' stage of change in four TCC activities: asking,
      advising, assisting, and arranging follow-up. Pros and cons affecting the
      delivery of TCC were also examined. Findings indicate that dental hygienists who
      received TCC education during their training do not provide cessation counseling
      to a high percentage of their patients even though they believe in the value of
      such activity. However, dental hygienists are more likely to provide TCC to
      patients with periodontal disease than other dental patients. CONCLUSIONS: 1)
      addressing the potential frustration of the dental hygienist and coping methods
      when providing TCC during training may alleviate one of the barriers to TCC; 2)
      ready access to tobacco education materials may alleviate one of the barriers to
      TCC; and 3) emphasis during TCC training on providing education for all patients
      as part of health promotion, rather than just periodontal patients, may increase
      the overall counseling provided.

PMID- 16081574
TI  - Improving patient retention and access to oral health care: the CARES program.
AB  - Improving access to dental care for patients experiencing barriers such as
      financial, transportation, or mental health is a public health concern. Dental
      schools have an obligation to assist patients experiencing such barriers as well
      as to educate future dentists and allied professionals on how to assist these
      patients in overcoming barriers. Once admitted to the dental clinic, retention
      issues can further complicate the provision of dental care. This article will
      describe an innovative program designed to address biopsychosocial barriers to
      dental care. Needs assessments of patients sitting in the waiting room of the
      dental clinic were conducted by master's of social work (M.S.W.) students. Based
      on needs assessment results, common dental care barriers were identified and
      served as the foundation for the establishment of a social work program in the
      dental clinic. Dental students, faculty, and staff refer patients to the social
      work program when barriers to care are found. These biopsychosocial barriers are
      addressed by social workers, uniquely qualified professionals in providing case
      management, advocacy, referrals, education, and services (CARES). Over the course
      of three years, 80 percent of patients experiencing an identified barrier to the
      receipt of dental care were retained through social work intervention. These
      patients were able to receive dental care within the past year. Dental schools
      can collaborate with social work schools to establish a protocol and assistance
      program for dental patients experiencing difficulty accessing care, thereby
      improving oral health status, retention rates, and dental student education.

PMID- 16081575
TI  - Cancer therapy-related oral mucositis.
AB  - Oral mucositis is a common side effect of cancer therapies, particularly
      radiation therapy for head and neck cancer and various forms of chemotherapy. It
      commonly results in severe oral pain that can compromise the duration and success
      of cancer management. Hospitalizations are common because patients lose the
      ability to take anything by mouth due to severe pain and must have alimentation
      supported during this period. Pain management usually requires potent narcotic
      analgesia. Cancer therapy-related oral mucositis is commonly described as the
      most significant and debilitating acute complication associated with radiation
      therapy and chemotherapy. Until recently, cancer therapy-induced oral mucositis
      was thought to be a process involving the epithelium only. Evidence is building
      that the process of oral mucositis involves far more than just the epithelium,
      but includes multiple cellular processes of the submucosa as well. Many
      strategies have been evaluated to prevent oral mucositis, but the data is
      confusing since it is often conflicting. Therapy with the growth factor, KGF1,
      appears promising, as it is the only medication currently approved by the FDA. A
      multifaceted approach that targets the entire mucositis process will probably be
      needed to optimize overall prevention.

PMID- 16081576
TI  - Comparison of written examinations required for dental licensure in Japan and the
      United States: contents, cognitive levels, and cultural implications.
AB  - The goal of this article is to describe differences between the written
      examinations required for dental licensure in Japan and in the United States.
      Candidate guides, old exams, and other published data pertaining to the Japan
      National Examination for Dentists (NED) and the U.S. National Board Dental
      Examination (NBDE) were used. Dental education in Japan consists of a six-year
      program following high school graduation. The U.S. counterpart is usually a four
      year program following a bachelor's degree. The NED, which is made up of 330
      questions, is a single, all-important gatekeeper test that immediately grants
      licensure to practice dentistry throughout Japan. The NED contains no evaluation
      of technical skills; it is purely a written exam. By contrast, in the United
      States, the NBDE Parts I and II, which consist of 900 questions, are only
      components of a three-step licensure process. An additional state or regional
      board examination on technical skills is required to obtain licensure to
      practice. There are 400 basic science questions on the NBDE Part I, while the NED
      has thirty. In terms of cognitive level, questions on the NED place more emphasis
      on recall, while those on the NBDE Part II are more focused on problem solving.
      The outcomes of this comparison provide dental educators with comparisons of the
      licensure examination process for Japanese and U.S. dentists.

PMID- 16081577
TI  - Intracellular antibodies (intrabodies) versus RNA interference for therapeutic
      applications.
AB  - Currently there are two technology platforms for the ablation of protein
      function: (a) RNAi-mediated gene-silencing at the post-transcriptional level, and
      (b) intrabody knockout of protein function at the post-translational level. Both
      approaches hold much promise for therapeutic applications. The pertinent question
      is how to choose between these alternative approaches. This commentary examines
      the advantages and disadvantages of these newly-emerging technology platforms.
      The RNAi approach is much less technically challenging than the intrabody
      mediated knockout of protein function, but its major limitation is non
      specificity. Although it is time-consuming and labor-intensive to generate
      intrabodies for specific intracellular protein targets, a much higher level of
      specificity can be attained. Ultimately, the choice between these strategies
      depend on the specific application in question, as well as on further technical
      advances in both technology platforms.

PMID- 16081578
TI  - Global genomic approaches to the iron-regulated proteome.
AB  - Iron interacts with cells to regulate the proteome through complex effects on
      gene expression. In simple organisms such as bacteria and yeast, intra- and extra
      cellular iron influences gene expression through defined signal transduction
      pathways. In higher organisms, effects are probably mediated at the
      transcriptional level through secondary effects of reactive oxygen species, while
      post-transcriptional effects operate through well-defined pathways involving iron
      regulatory proteins. To investigate the impact of iron levels on gene expression
      and the proteome, approaches such as differential display and subtractive
      hybridization have the advantage of surveying the entire genome. However, they
      are technically demanding and have given way to microarray techniques. To date,
      numerous microarray experiments with various organisms have not yielded any
      definitive picture of the role of iron. Common themes throughout such studies are
      that both iron excess and iron depletion influence expression of proteins related
      to energy metabolism, cell proliferation, matrix structure, and the metabolism of
      iron itself. That no consistent set of genes is involved from one study to the
      next probably results both from the uncertainties inherent in the technique and
      the biological variability of the systems under study. We briefly describe two
      types of iron-dependent microarray experiments from our laboratory to examine
      major cellular targets of iron toxicity. Using Affymetrix oligonucleotide arrays
      with cardiac cells, we found several hundred genes whose mRNA levels were
      affected by iron, including an increase in several genes responding to oxidative
      stress and a decrease in several kinases and phosphatases. In a simpler
      experiment using a human liver cell line with a limited cDNA array, we targeted
      13 genes affected by iron chelation. Metabolic pathway analysis shows links of 5
      of these through phorbol ester responsiveness, and additional links through
      prostaglandin E2. We conclude that definitive understanding of the complex iron
      regulated proteome requires global gene approaches and rigorous interlaboratory
      standardization.

PMID- 16081579
TI  - Association of soluble markers with various stages and major events of
      atherosclerosis.
AB  - The purpose of this review is to identify soluble markers from the recent
      literature that facilitate the early prevention and early detection of
      atherosclerosis, and that may serve as therapeutic targets. Soluble markers
      associated with various stages and major events of atherosclerosis were
      identified. We divided the process of atherosclerosis into several stages,
      including stages for the early risk, plaque expansion, and stable and unstable
      angina-though excluding the end stage of myocardial infarction. For major events
      taking place prior to and during the progression of atherosclerosis we included
      events such as endothelial dysfunction in the artery, expression of adhesion
      molecules at the injured endothelium, continued inflammatory responses, oxidative
      stress, and ischemia. We found that reactions such as cell injury, adhesion,
      inflammation, and oxidative stress occur not only at the early stage of risk but
      persist throughout the process of atherosclerosis. Most markers associated with
      these major events are clustered together at any time of the disease. Few markers
      are characteristic of individual stages. We noted that reactions such as
      inflammation are continuously intensified with the progression of the disease.
      Finally, we underscore the importance of measuring a panel consisting of minimal
      numbers of multiple markers with the maximal sensitivity for early risk
      assessment, diagnosis, and prognosis. We envision that patterns characteristic of
      various stages of atherosclerosis may be identifiable with the use of the
      multiple markers described in this review.

PMID- 16081580
TI  - Nuclear factor-kappaB pathway as a therapeutic target in head and neck squamous
      cell carcinoma: pharmaceutical and molecular validation in human cell lines using
      Velcade and siRNA/NF-kappaB.
AB  - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is synthesized in the cytoplasm,
      complexed with its inhibitor, I-kappaB, and NF-kappaB is released in an activated
      (phosphorylated) form following phosphorylation of I-kappaB and proteasomal
      degradation of the NF-kappaB.p-kappaB complex. The free p-NF-kappaB can then be
      translocated to the nucleus where it effects transcriptional activation of genes
      leading to the synthesis of proteins that are generally pro-growth and anti
      apoptosis. OBJECTIVE: To gain insight into the role of the NF-kappaB pathway in
      head and neck squamous cell carcinoma (HNSCC), we selected two HNSCC cell lines,
      SCC-15 of lingual origin and FaDu of pharyngeal origin, with constitutively
      activated (phosphorylated) NF-kappaB. We assessed the impact of interrupting the
      NF-kappaB pathway at the level of proteasomal degradation using Velcade
      (bortezomib), a proteasome inhibitor, and at the pretranslational level in the
      synthesis of NF-kappaB using a small interfering RNA (siRNA). RESULTS: Velcade
      produced a dose-dependent inhibition of cell growth in both cell lines. At 30 nM,
      Velcade inhibited cell growth in the SCC-15 cell line by 40%. In both cell lines,
      Velcade induced nuclear overexpression of p21(WAF1), an inhibitor of G1 cell
      cycle progression, which appeared to be independent of p53 expression. Addition
      of siRNA augmented the inhibitory effects of Velcade in FaDu cells; siRNA/NF
      kappaB alone led to a 48% decline in basal expression of NF-kappaB protein levels
      and effected a 25% inhibition of cell growth. In the presence of Velcade (30 nM),
      siRNA/NF-kappaB increased growth inhibition from 43 to 65%. CONCLUSIONS: The
      mechanisms involved in growth inhibitory effects of Velcade on HNSCC cell lines
      include the NF-kappaB pathway, suggesting the possible therapeutic use of Velcade
      or other NF-kappaB pathway inhibitors (eg, curcumin). The data also suggest that
      combining siRNA/NF-kappaB with Velcade might achieve greater reduction in the
      growth of HNSCC in patients with constitutively activated NF-kappaB.

PMID- 16081581
TI  - CT60 single nucleotide polymorphism of the CTLA-4 gene is associated with
      susceptibility to Graves' disease in the Taiwanese population.
AB  - Graves' disease (GD) is an autoimmune disease but the underlying etiology has not
      been completely elucidated. Genetic susceptibility has been believed to play a
      major role. Recent studies showed that the CT60 single nucleotide polymorphism
      (SNP), which is in the 3'-noncoding region of the CTLA-4 gene, is strongly
      associated with some immune-mediated diseases. The aim of this study was to test
      for association between GD susceptibility and polymorphisms of CTLA-4 (ie, the
      CT60 SNP and the exon 1 +49 SNP) in the Taiwanese population. Our results
      demonstrate significant differences in the frequencies of the genotypes and
      alleles between 107 GD patients and 101 control subjects in the CT60 and exon 1
      +49 SNPs (p <0.05). Significant differences in phenotypes were only found for
      CT60 SNP (78.4% vs 67.8% between patients and controls; chi2 = 3.93, p = 0.047).
      Furthermore, we found that the G/G genotype of both CT60 and exon 1 +49 was
      associated with increased risk for GD (p = 0.022, OR = 1.97). Significant linkage
      disequilibrium was found between the CT60 SNP and the exon 1 +49 SNP in both GD
      patients and control subjects (D' = 1.00). Because of tight linkage
      disequilibrium, a combination of these SNPs enhanced the role of the CTLA-4 gene
      in GD. The frequency of the disease-susceptible G allele of CT60 was comparable
      to that in Japanese and higher than in Caucasians. In conclusion, we provide
      evidence that CT60 SNP is associated with susceptibility to GD in the Taiwanese
      population.

PMID- 16081582
TI  - Identification of a novel B variant allele at the ABO locus in Chinese Han
      individuals with B subgroup.
AB  - We studied the molecular genetic background of the B subgroup in the Chinese Han
      population and identified a novel allele at the ABO locus. Ten control samples
      from randomly selected blood donors of normal B phenotype and 6 samples from
      individuals diagnosed as B subgroup by serological tests were genotyped by PCR
      SSP and direct DNA sequencing at exons 6 and 7 of the ABO gene. Exons 6 and 7 and
      the intervening intron 6 of B alleles from the 6 B subgroup samples were analyzed
      by cloning and haplotype-sequencing. A novel B variant allele was identified in 2
      individuals who were serologically-determined as members of the B(x) and B(w)
      subgroups, respectively. The novel B allele differs from allele B101 by a single
      695T>C missense mutation in exon 7. The family of the individual with B(x)
      subgroup was studied; among 8 family members tested, 4 had the novel B variant
      allele. No mutation at exon 6 or 7 of the ABO gene was detected in the 10 control
      samples or in the other 4 B subgroup samples. Mutation at position 695 where T is
      replaced by C results in an amino acid change from Leu to Pro, which is predicted
      to diminish B transferase activity. This indicates that alteration of the amino
      acid at position 232 is critical to the activity of glycosyltransferases.

PMID- 16081583
TI  - SMYD3-NY, a novel SMYD3 mRNA transcript variant, may have a role in human
      spermatogenesis.
AB  - Identification of genes specifically expressed in adult and fetal testis is
      important to further our understanding of testis development and function. In
      this study, a novel SMYD3 transcript variant, termed SMYD3-NY (GenBank Accession
      No. AY186742), was identified by hybridization of adult and fetal human testis
      cDNA probes with a human cDNA microarray. SMYD3-NY transcript was expressed at
      2.3-fold higher levels in adult human testis than in fetal testis, with a low
      expression level in human spermatozoa. Bioinformatical analysis showed that SMYD3
      NY protein has the SET domain that is involved in histone methyltransferase
      (HTMase) activity. Southern blotting showed that SMYD3-NY is distributed in
      several tissues, including testis. In summary, SMYD3-NY is a novel transcript
      variant of the SMYD3 gene, and SMYD3-NY protein may influence transcriptional
      regulation during spermatogenesis via HTMase activity.

PMID- 16081584
TI  - Decoy androgen-responsive element DNA can inhibit androgen receptor
      transactivation of the PSA promoter gene.
AB  - Chemotherapy, hormonal therapy, or surgery may cause devastating toxic or other
      side effects. Androgen receptors (ARs) in the cytoplasm are activated by binding
      with androgen. Androgen-activated ARs bind to a specific genomic DNA sequence,
      the androgen-responsive element (ARE), and initiate gene expression at the
      transcriptional level. Even without androgen activation, ARs may have a role in
      androgen-refractory prostate cancer. Thus, inhibition of AR activity may have
      therapeutic value. We applied a genetic reporter of the Dual-Luciferase Assay
      System to test whether a short double-stranded genomic DNA containing prostate
      specific antigen (PSA) ARE sequence as decoy DNA would inhibit the function of
      activated AR. A 21-mer phosphorothioated PSA ARE decoy DNA was synthesized, with
      a plasmid vector containing the PSA promoter upstream from a luciferase gene, the
      reporter gene. The promoter and reporter were co-transfected into a human
      prostate cancer cell line PC3-M with the aid of Lipofectamin 2000. After 24 hr
      exposure to androgens, the cells were lysed and luciferase activity measured to
      determine the ARE decoy inhibitory effect on the function of ARs. Luciferase
      activity was reduced significantly in the ARE decoy transfected cells but not
      with inactive control decoy. The results demonstrate that ARE decoy DNA can
      effectively suppress androgen-activated ARs in prostate cancer cells and indicate
      the potential utility of decoy DNA for developing a novel therapy for prostate
      cancer.

PMID- 16081585
TI  - Tapering dose of inhaled budesonide in subjects with mild-to-moderate persistent
      asthma treated with montelukast: a 16-week single-blind randomized study.
AB  - Pharmacological therapy with inhaled steroids (IS) is currently considered the
      gold-standard of treatment for mild-persistent asthma. Leukotriene receptor
      antagonist drugs (LTRAs) play an important role associated with IS, allowing dose
      tapering and maintaining control of asthma symptoms. The aim of this study was to
      determine the effectiveness of montelukast (MON) to allow tapering of the inhaled
      dose of budesonide (BUD) in patients with mild-moderate persistent asthma. This
      16-wk single-blind randomized study included 40 asthmatic patients divided in 2
      treatment groups. After a run-in period (4 wk), in which all patients inhaled 400
      microg of BUD twice daily (bid), group A (20 patients) received MON (oral, 10
      mg/day) combined with inhaled BUD (400 microg/bid), while group B (20 patients)
      was treated with BUD for the whole period of the study. In both groups, at every
      4 wk the dose of BUD was halved. After 12 wk of treatment the mean value of
      forced expiratory volume during the first sec (FEV1, as % of predicted value) was
      significantly greater in group A compared with group B (94 +/- 7.5 vs 83.1 +/-
      6.9; p<0.005). The mean values of peak expiratory flow (PEF), the percentages of
      asthmatic exacerbations, and the use of beta2-short-acting agonist (SABA) were
      similar in the 2 groups at 4, 8, and 12 wk. In conclusion, in patients with mild
      moderate persistent asthma, MON therapy is useful in tapering the dose of IS in
      order to reduce its side effects and to maintain the clinical stability of the
      disease.

PMID- 16081586
TI  - Relationships of soluble APO-1 (Fas/CD95) concentrations, obesity, and serum
      lipid parameters in healthy adults.
AB  - To investigate the relationships of apoptosis with obesity and lipid parameters,
      we measured serum soluble APO-1 (sAPO-1) concentrations, body mass index (BMI),
      and serum lipid profiles in 176 healthy adults. Serum sAPO-1 levels were measured
      by enzyme immunoassay. There were no significant differences in mean sAPO-1
      concentrations between men and women, nor between subjects with and without
      obesity. However, women with high-density lipoprotein cholesterol (HDL-C) <50.2
      mg/dl exhibited significantly higher sAPO-1 concentrations than those with HDL-C
      >50.2 mg/dl (ie, 45.6 +/- 10.4 pg/ml vs 31.5 +/- 11.3 pg/ml, p <0.05). Serum sAPO
      1 concentrations averaged 46.8 +/- 10.7 pg/ml in women with serum triglyceride
      >137.4 mg/dl, which was significantly above the mean value (32.6 +/- 12.0 pg/ml,
      p <0.05) in those with serum triglyceride <137.4 mg/dl. Men with elevated sAPO-1
      concentrations showed significantly higher waist-to-hip ratio (WHR) and total
      body fat (TBF) compared to those with diminished sAPO-1 levels, although no
      differences were noted in mean values of lipid profiles between the 2 groups of
      men. Serum sAPO-1 concentrations correlated significantly with HDL-C (r = - 0.41,
      p <0.05) and triglyceride (r = 0.35, p <0.05) in women and WHR (r = 0.25, p
      <0.05) and TBF (r = 0.21, p <0.05) in men. In conclusion, serum sAPO-1 appears to
      have an important relationship to serum lipid levels and body adiposity in
      healthy adults.

PMID- 16081587
TI  - Nosocomial transmission of CTX-M-15 and OXA-30 beta-lactamase-producing
      Escherichia coli in a neurosurgical intensive care unit.
AB  - Extended-spectrum beta-lactamase-producing E. coli were recovered from 16
      patients in a neurosurgical intensive care unit; surveillance cultures revealed
      that the organism could be transmitted through the contaminated environment and
      the hands of health care personnel. All isolates from the patients, environment,
      and health care personnel showed the same pulsed-field gel electrophoresis
      pattern. Isoelectric focusing, PCR analysis,and sequencing demonstrated that this
      E. coli harbored CTX-M-15 and OXA-30 beta-lactamases that were transferred by
      conjugation. This is the first report of nosocomial transmission caused by E.
      coli that harbor the combination of CTX-M-15 and OXA-30. This can be a threat
      because the organisms can hydrolyze cefotaxime, ceftazidime, and cefepime.

PMID- 16081588
TI  - Flow cytometry of Candida albicans for investigations of surface marker
      expression and phagocytosis.
AB  - Several cytoplasmic virulence factors of Candida albicans are altered in the
      presence of estrogen and this fact may imply the existence of a global virulence
      regulatory system in this organism. The response of virulence-associated surface
      markers to estrogen, however, has not been studied. We exploited flow cytometry
      methods for assessment of the iC3b receptor analog and mannoproteins on 2
      clinical yeast strains selected for their different rates of growth in the
      presence of estradiol 17beta. Although, as expected, iC3b receptor analog
      expression increased in the presence of glucose, growth in the presence of
      estradiol did not increase the levels of iC3b receptor analog on either organism.
      Exposure to human serum caused massive conversion to mycelial growth, but cells
      examined by flow cytometry did not show increased levels of iC3b receptor analog
      expression, possibly due to inability of the flow cytometer to sample the
      mycelial forms of Candida. In contrast, estradiol increased expression of
      mannoproteins as evidenced by concanavalin A binding to yeast. This increase
      occurred in both yeast strains but was less pronounced with strain GT188, which
      also showed limited growth in estradiol compared to strain GT142. Effective
      phagocytosis by human neutrophils required exposure of yeast to human serum.
      Yeast grown in the presence of estradiol were ingested by human PMN but not at a
      significantly greater rate than yeast grown without estradiol. While flow
      cytometry appears to be useful in determining estrogen-enhanced concanavalin A
      binding to yeast, it probably does not reflect the surface markers on large
      mycelial masses. Consequently, the results of this study are applicable to
      Candida primarily in its yeast form.

PMID- 16081589
TI  - Microplate ELISAs for soluble VCAM-1 and ICAM-1.
AB  - Soluble vascular cell adhesion molecule (sVCAM-1) and soluble intercellular
      adhesion molecule (sICAM-1) are adhesion molecules that are detectable in the
      serum of patients with cancer, cardiovascular diseases (CVD), and type 2
      diabetes. This report describes enzyme-linked immunosorbent assays (ELISAs) on
      microplates for sVCAM-1 and sICAM-1. The ELISAs have the sandwich test format;
      polyclonal antibodies are coated on microwells and a one-step procedure is used
      in which the serum specimen and detecting antibody are added simultaneously to an
      antibody-coated well. These assays both use HRP-conjugated sheep anti-mouse-IgG
      to generate the color for quantification. Sensitivities for detecting sVCAM-1 and
      sICAM-1 are 49 and 40 ng/ml, respectively. Coefficients of variation for within
      day and day-to-day replicate analyses are <10%. Results by these in-house ELISAs
      for serum sVCAM-1 and sICAM-1 compared well with those obtained with commercial
      kits from R&D Systems, Inc. (correlation coefficients = 0.98 and 0.99 for sVCAM-1
      and sICAM-1, respectively). Reference values for serum sVCAM-1 and sICAM-1 levels
      were measured in 369 apparently healthy Chinese adults, age 30 to 79 yr. There
      was no significant effect of gender on the reference values for sVCAM-1 or sICAM
      1. Serum sVCAM-1 levels (mean +/- SD) were higher in subjects 60 yr old (625 +/-
      126 ng/ml), compared to those <60 yr old (525 +/- 110 ng/ml) (p <0.001). Age did
      not significantly affect the reference values for serum sICAM-1 levels (mean +/-
      SD, 249 +/- 86 ng/ml). The authors believe that these simple, inexpensive ELISAs
      will be useful for assessing the risks for development of cancer, CVD, and type 2
      diabetes.

PMID- 16081590
TI  - Comparison of VIDAS Stallertest and Pharmacia CAP assays for detection of
      specific IgE antibodies in allergic children.
AB  - In vitro determination of specific IgE antibodies in serum is the most frequently
      used method, besides the skin test, for diagnosing allergies. Standardized and
      reproducible assays of specific IgE antibodies contribute to the quality of
      diagnosis and treatment of allergic disease. This study compared the results and
      performance characteristics of the Pharmacia CAP system and a new specific IgE
      method using the VIDAS Stallertest (manufactured by bioMeriux). To evaluate their
      clinical efficiency, the results of the CAP and VIDAS Stallertest assays were
      compared with skin prick test (SPT) results. After allergic patients completed
      SPTs, serum samples were collected and CAP and VIDAS Stallertest assays were
      performed to determine specific IgEs for Dermatophagoides farinae, D.
      pteronyssinus, cockroach, and alternaria. For egg and milk, we measured only the
      correlation between the 2 in vitro assays. When SPT was used as a reference
      standard, the sensitivity and specificity of the CAP assay was a little higher in
      respect to all inhalant allergens. There were significant correlations between
      the results of VIDAS Stallertest and CAP assays for IgE antibodies to inhalant
      and food allergens. This study indicates that the VIDAS Stallertest and Pharmacia
      CAP assays are feasible and replicable for measuring allergen-specific IgE.

PMID- 16081591
TI  - Bile acid biosynthesis during liver regeneration: enzyme activities of
      cholesterol 7alpha-hydroxylase and 3beta-hydroxy-delta5-C27-steroid dehydrogenase
      in rats.
AB  - The effects of two-thirds partial hepatectomy on bile acid metabolism have not
      been well established. This study investigated the changes in microsomal enzymes
      activities during liver regeneration. The cholesterol 7alpha-hydroxylase (7alpha
      hydroxylase) and 3beta-hydroxy-delta5-C27-steroid dehydrogenase (3beta
      dehydrogenase) activities in male Wistar rats were determined using high
      performance liquid chromatography (HPLC). Cytochrome P450 (P450) and cytochrome
      b5 (b5) levels and NADPH cytochrome c reductase activities were also determined
      after hepatectomy. 7alpha-Hydroxylase activities were not reduced on days 3, 5,
      or 7 compared to those of sham-operated rats, but there was a significant
      decrease (by 60%) of 3beta-dehydrogenase activity compared to that of sham
      operated groups (p <0.01) on days 3, 5, and 7 after hepatectomy. While 7alpha
      hydroxylase activity had recovered by day 3 after hepatectomy, 3beta
      dehydrogenase activity had not, even on day 7. These results suggest that the
      mechanisms of regulation of these 2 bile acid metabolizing enzymes are
      significantly different during liver regeneration.

PMID- 16081592
TI  - Aminoguanidine prevents ototoxicity induced by cisplatin in rats.
AB  - Cisplatin (CDDP) is one of the most potent antineoplastic drugs, but its
      therapeutic use is limited by side effects such as ototoxicity. This study tested
      the effect of aminoguanidine (AG), a specific inhibitor of inducible nitric oxide
      synthase, on CDDP ototoxicity. Female Wistar albino rats were randomly assigned
      to 4 groups: saline controls (n = 7), CDDP (n = 7), CDDP plus AG (n = 7), and AG
      (n = 7). Rats in the CDDP group received a single injection of cisplatin (16
      mg/kg, ip). Rats in the CDDP plus AG group received aminoguanidine (20 mg/kg, ip)
      twice daily on the day before and on 5 consecutive days after a single injection
      of CDDP (16 mg/kg, ip). Rats in the AG group received aminoguanidine (20 mg/ kg,
      ip) twice daily for 6 days. Distortion product otoacoustic emissions (DPOAEs)
      were elicited from the control and experimental animals utilizing a standard
      commercial otoacoustic emissions apparatus. DPOAEs were measured in the rats on
      day 0, prior to any drug administration, and on day 5. The initial baseline
      distortion product diagrams (DPgram) and input/output (I/O) function measurements
      gave similar results in all 4 groups. On day 5, there was significant
      deterioration of the DPgrams and I/O functions in the CDDP group; no significant
      changes of DPgrams and I/O functions were observed on day 5 in the other 3
      groups. The median amplitudes of DPgrams and I/O functions revealed significant
      differences between the CDDP group and the other 3 groups. These results suggest
      that AG had a preventive effect against CDDP ototoxicity. In summary, this study
      indicates that AG prevents the cochlear dysfunction and hearing loss induced in
      rats by a single dose of CDDP.

PMID- 16081593
TI  - The story of bronchioloalveolar carcinoma.

PMID- 16081594
TI  - The role of TNF in hepatic histopathological manifestations and hepatic CD8+ T
      cell alloresponses in murine MHC class I disparate GVHD.
AB  - Transfer of B6 T cells to major histocompatibility complex (MHC) class I
      disparate bm1 x B6 F1 mice leads to the development of hepatic graft-versus-host
      disease (GVHD) characterized by an active hepatitis with portal and lobular
      inflammation as well as bile duct inflammation and venulitis. The present studies
      determined the role of tumor necrosis factor (TNF) in hepatic GVHD. B6 responder
      cells were cultured with irradiated MHC class I disparate bm1 or syngeneic spleen
      cells (SpC) in the presence or absence of TNF receptor inhibitor [TNFR
      immunoglobulin (Ig)]. Recipient bm1 x B6 F1 mice were irradiated (600 cGy) and
      reconstituted with 5 x 10(6) T cell-depleted B6 bone marrow cells and 1 x 10(7)
      B6 SpC. Mice were injected with an adenovirus encoding TNFR-Ig [TNF inhibitor
      encoding adenovirus (Adv-TNFi)] or beta-galactosidase (Adv-betagal). Severity of
      liver GVHD was assessed by a composite histopathological score consisting of the
      sum of scores for venulitis, lobular hepatitis, and bile duct inflammation.
      Addition of TNFR-Ig reduced cell proliferation in mixed lymphocyte cultures using
      B6 responder SpC by 71% +/- 12.8% and interferon-gamma responses by 78% +/- 18%.
      GVHD-induced "wasting disease" was reduced in Adv-TNFi recipients [4.4%+/-5.2%
      weight loss (n=11)] compared with Adv-betagal recipients [16.1%+/-7.6% weight
      loss (n=11; P=0.0004)] 9 days post-transplant. Composite histopathological scores
      and individual venulitis scores were reduced with the addition of Adv-TNFi.
      Hepatic CD8+ T cells in the recipients of Adv-TNFi were reduced as compared with
      recipients of Adv-betagal. In conclusion, Adv-TNFi reduces MHC class I disparate
      alloproliferative responses and hepatic GVHD.

PMID- 16081596
TI  - Blockade of CTLA-4 (CD152) enhances the murine antibody response to pneumococcal
      capsular polysaccharides.
AB  - The capsular polysaccharides (caps-PS) of Streptococcus pneumoniae are classified
      as thymus-independent antigens. Nevertheless, T lymphocytes can modulate the
      antibody response to caps-PS. In this study, we show that anticytotoxic T
      lymphocyte-associated antigen 4 (CTLA-4) treatment, along with administration of
      caps-PS to BALB/c mice, resulted in a dose-dependent generation of a strong caps
      PS-specific antibody response. Anti-CTLA-4 treatment had no effect on the
      immunoglobulin G (IgG) antibody production in athymic nu/nu mice. Anti-CTLA-4
      treatment stimulated the IgG antibody production in severe combined
      immunodeficiency (SCID)/SCID mice reconstituted with CTLA-4(-/-) B lymphocytes
      and wild-type T lymphocytes. This excluded the possibility that anti-CTLA-4
      enhanced antibody production by direct interaction with B lymphocytes. Anti-CTLA
      4 treatment enhanced the antibody production in SCID/SCID mice reconstituted with
      B lymphocytes and CD4(+) and CD8(+) T lymphocytes but not in SCID/SCID mice
      reconstituted with B lymphocytes in the absence of CD4(+) and/or CD8(+) cells.
      Administration of anti-CTLA-4 in BALB/c mice but not in nu/nu mice resulted in a
      markedly increased production of interleukin (IL)-2, IL-4, and interferon-gamma.
      Taken together, these data strongly suggest a role of T lymphocytes and CTLA-4 in
      the regulation of the antibody response to caps-PS.

PMID- 16081595
TI  - Enhanced superoxide release and elevated protein kinase C activity in neutrophils
      from diabetic patients: association with periodontitis.
AB  - Inflammation and oxidative stress are important factors in the pathogenesis of
      diabetes and contribute to the pathogenesis of diabetic complications.
      Periodontitis is an inflammatory disease that is characterized by increased
      oxidative stress, and the risk for periodontitis is increased significantly in
      diabetic subjects. In this study, we examined the superoxide (O(2)(-))-generating
      reduced nicotinamide adenine dinucleotide phosphate-oxidase complex and protein
      kinase C (PKC) activity in neutrophils. Fifty diabetic patients were grouped
      according to glycemic control and the severity of periodontitis. Neutrophils from
      diabetic patients with moderate [amount of glycated hemoglobin (HbA(1c)) between
      7.0% and 8.0%] or poor (HbA(1c) >8.0%) glycemic control released significantly
      more O(2)(-) than neutrophils from diabetic patients with good glycemic control
      (HbA(1c) <7.0%) and neutrophils from nondiabetic, healthy individuals upon
      stimulation with 4beta-phorbol 12-myristate 13-acetate or N-formyl-Met-Leu-Phe.
      Depending on glycemic status, neutrophils from these patients also exhibited
      increased activity of the soluble- and membrane-bound forms of PKC, elevated
      amounts of diglyceride, and enhanced phosphorylation of p47-phox during cell
      stimulation. In addition, we report a significant correlation between glycemic
      control (HbA(1c) levels) and the severity of periodontitis in diabetic patients,
      suggesting that enhanced oxidative stress and increased inflammation exacerbate
      both diseases. Thus, hyperglycemia can lead to a novel form of neutrophil
      priming, where elevated PKC activity results in increased phosphorylation of p47
      phox and O(2)(-) release.

PMID- 16081597
TI  - Virus overrides the propensity of human CD40L-activated plasmacytoid dendritic
      cells to produce Th2 mediators through synergistic induction of IFN-{gamma} and
      Th1 chemokine production.
AB  - Depending on the activation status, plasmacytoid dendritic cells (PDC) and
      myeloid DC have the ability to induce CD4 T cell development toward T helper cell
      type 1 (Th1) or Th2 pathways. Thus, we tested whether different activation
      signals could also have an impact on the profile of chemokines produced by human
      PDC. Signals that induce human PDC to promote a type 1 response (i.e., viruses)
      and a type 2 response [i.e., CD40 ligand (CD40L)] also induced PDC isolated from
      tonsils to secrete chemokines preferentially attracting Th1 cells [such as
      interferon-gamma (IFN-gamma)-inducible protein (IP)-10/CXC chemokine ligand 10
      (CXCL10) and macrophage inflammatory protein-1beta/CC chemokine ligand 4 (CCL4)]
      or Th2 cells (such as thymus and activation-regulated chemokine/CCL17 and
      monocyte-derived chemokine/CCL22), respectively. Activated natural killer cells
      were preferentially recruited by supernatants of virus-activated PDC, and
      supernatants of CD40L-activated PDC attracted memory CD4(+) T cells, particularly
      the CD4(+)CD45RO(+)CD25(+) T cells described for their regulatory activities. It
      is striking that CD40L and virus synergized to trigger the production of IFN
      gamma by PDC, which induces another Th1-attracting chemokine monokine-induced by
      IFN-gamma/CXCL9 and cooperates with endogenous type I IFN for IP-10/CXCL10
      production. In conclusion, our studies reveal that PDC participate in the
      selective recruitment of effector cells of innate and adaptive immune responses
      and that virus converts the CD40L-induced Th2 chemokine patterns of PDC into a
      potent Th1 mediator profile through an autocrine loop of IFN-gamma.

PMID- 16081598
TI  - The effects of CpG DNA on HMGB1 release by murine macrophage cell lines.
AB  - DNA containing cytosine-guanine dinucleotide (CpG) motifs (CpG DNA) has potent
      immunostimulatory activities that resemble those of lipopolysaccharide (LPS) in
      its effects on the innate immune system. Among its activities, LPS can induce the
      release of high mobility group protein (HMGB1) by macrophages, a dual function
      molecule that can mediate the late effects of LPS. To determine whether CpG DNA
      can also induce HMGB1 release, the effects of a synthetic CpG oligonucleotide
      (ODN) on HMGB1 release from RAW 264.7 and J774A.1 cells were assessed by Western
      blotting of culture supernatants. Under conditions in which the CpG ODN activated
      the cell lines, as assessed by stimulation of tumor necrosis factor alpha and
      interleukin-12, it failed to cause HMGB1 release into the media. Although unable
      to induce HMGB1 release by itself, the CpG ODN nevertheless potentiated the
      action of LPS. With RAW 264.7 cells, lipoteichoic acid and polyinosinic
      polycytidylic acid, like LPS, stimulated HMGB1 release as well as cytokine
      production. These results indicate that the effects of CpG DNA on macrophages
      differ from other ligands of Toll-like receptors and may lead to a distinct
      pattern of immune cell activation in the context of infection or its use as an
      immunomodulatory agent.

PMID- 16081599
TI  - HIV-1 gp120-induced TNF-{alpha} production by primary human macrophages is
      mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein
      (MAP) kinase pathways.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection is initiated by binding of
      the viral envelope glycoprotein gp120 to CD4 followed by a chemokine receptor,
      but these interactions may also take place independently from infection. gp120
      stimulation of primary human macrophages is known to trigger production of
      cytokines implicated in pathogenesis, particularly tumor necrosis factor alpha
      (TNF-alpha), but the mechanisms have not been determined. We sought to define the
      pathways responsible for TNF-alpha secretion by monocyte-derived macrophages
      (MDM) following HIV-1 gp120 stimulation. MDM exposure to recombinant macrophage
      tropic (R5) gp120 led to dose- and donor-dependent release of TNF-alpha, which
      was cyclohexamide-sensitive and associated with up-regulated message.
      Pretreatment with specific inhibitors of the mitogen-activated protein kinases
      (MAPK) extracellular signal-regulated kinase 1/2 (ERK-1/2; PD98059, U0126) and
      p38 (SB202190, PD169316) inhibited the secretion of TNF-alpha. gp120-elicited TNF
      alpha production was also blocked by phosphatidylinositol-3 kinase (PI-3K)
      inhibitors (wortmannin, LY294002). Moreover, PI-3K inhibition ablated gp120
      induced phosphorylation of p38 and ERK-1/2. The response was inhibited by a CC
      chemokine receptor 5 (CCR5)-specific antagonist, indicating that CCR5 was in
      large part responsible. These results indicate that gp120-elicited TNF-alpha
      production by macrophages involves chemokine receptor-mediated PI-3K and MAPK
      activation, that PI-3K is an upstream regulator of MAPK in this pathway, and that
      p38 and ERK-1/2 independently regulate TNF-alpha production. These gp120
      triggered signaling pathways may be responsible for inappropriate production of
      proinflammatory cytokines by macrophages, which are believed to play a role in
      immunopathogenesis and in neurological sequelae of AIDS.

PMID- 16081600
TI  - In vivo rescue of defective memory CD8+ T cells by cognate helper T cells.
AB  - The magnitude and efficacy of CD8(+) T cell memory may notably regress,
      especially if immune induction occurs in the absence of adequate CD4(+) help.
      This report demonstrates that this CD8(+) memory malfunction could be remedied if
      a source of cognate antigen-recognizing helper cells were provided during recall.
      The inability of adoptive transfer of memory SIINFEKL-specific CD8 cells to
      reject tumors was overcome if recipients were primed for ovalbumin-specific
      helper cell responses. Additionally, animals primed for a SIINFEKL-specific
      memory response and incapable of rejecting the tumor could regain protective
      immunity if given helper cells. This pattern of CD8(+) T cell functional rescue
      or reprogramming by helper cell transfer was replicated using a Herpes simplex
      virus antiviral immunity system. Our results could mean that therapeutic vaccine
      approaches could be designed to compensate situations that have defective CD8(+)
      T cell function.

PMID- 16081601
TI  - Phylogenetic approaches in comparative physiology.
AB  - Over the past two decades, comparative biological analyses have undergone
      profound changes with the incorporation of rigorous evolutionary perspectives and
      phylogenetic information. This change followed in large part from the realization
      that traditional methods of statistical analysis tacitly assumed independence of
      all observations, when in fact biological groups such as species are
      differentially related to each other according to their evolutionary history. New
      phylogenetically based analytical methods were then rapidly developed,
      incorporated into ;the comparative method', and applied to many physiological,
      biochemical, morphological and behavioral investigations. We now review the
      rationale for including phylogenetic information in comparative studies and
      briefly discuss three methods for doing this (independent contrasts, generalized
      least-squares models, and Monte Carlo computer simulations). We discuss when and
      how to use phylogenetic information in comparative studies and provide several
      examples in which it has been helpful, or even crucial, to a comparative
      analysis. We also consider some difficulties with phylogenetically based
      statistical methods, and of comparative approaches in general, both practical and
      theoretical. It is our personal opinion that the incorporation of phylogeny
      information into comparative studies has been highly beneficial, not only because
      it can improve the reliability of statistical inferences, but also because it
      continually emphasizes the potential importance of past evolutionary history in
      determining current form and function.

PMID- 16081602
TI  - Behavioural discrimination of polarized light in the damselfish Chromis viridis
      (family Pomacentridae).
AB  - In this study, we demonstrate the capacity for damselfish (green chromis, Chromis
      viridis) to discriminate between different e-vector orientations of ultraviolet
      polarized light. We examined the ability of green chromis to resolve small
      differences in e-vector orientation of ultraviolet polarized light. Fish were
      successfully trained to swim towards an e-vector orientation of polarized light
      using a behavioural chamber. C. viridis was able to discriminate between the
      horizontal and the vertical plane of ultraviolet polarized light independent of
      brightness content of the stimuli. However, e-vector discrimination capability
      disappeared when the ultraviolet portion of the light stimuli was removed,
      indicating that the presence of ultraviolet light was critical for e-vector
      discrimination. Fish could also distinguish between relatively small e-vector
      orientations of ultraviolet polarized light. Functional implications for high e
      vector discriminative capabilities could be used in functional domains such as
      feeding and communication.

PMID- 16081603
TI  - Structure and function of the esophagus of the American alligator (Alligator
      mississippiensis).
AB  - Esophageal structure and function were studied in juvenile American alligators
      (Alligator mississippiensis). The anatomy of alligators differs from humans in
      several important aspects: the crocodilian esophagus is more muscular and is
      composed entirely of smooth muscle. Functionally, the crocodilian esophagus is
      similar to that of mammals, but alligators have peak esophageal peristaltic
      pressures that are 2-3-fold greater than pressures in the human esophagus. As is
      found in humans, the incidence of esophageal reflux increased in postprandial
      animals compared with the fasting state. We observed a large increase in pressure
      in the lower esophageal sphincter (LES) during ventilation that ranged from 200%
      to 3000% of the pressures measured during apnea. These pressure changes appear to
      be intrinsic to the LES. Alligators lack a mammalian-type diaphragm; thus, there
      is no crural diaphragmatic contribution to LES pressure. These features recommend
      the alligator as a useful model for the study of regulation of the LES.

PMID- 16081604
TI  - Computer simulations of high-pass filtering in zebrafish larval muscle fibres.
AB  - Larval somatic muscle of the zebrafish, Danio rerio, like that of some other
      organisms, responds to a sustained depolarization with one, and only one, action
      potential. Here, we report computer simulations, using the NEURON simulation
      programme, of sodium and potassium currents of somatic muscle of larval Danio
      rerio to investigate their possible contribution to once-only firing. Our
      computer model incorporated simulated sodium and potassium ion channels based on
      steady-state and kinetic parameters derived from a recent electrophysiological
      study. The model responded to sustained depolarizations with a single action
      potential at all levels of depolarization above threshold. By varying several
      parameters of the sodium and potassium currents systematically, the minimum
      changes necessary to produce repetitive firing were found to be a positive shift
      in the half-inactivation and a negative shift in the half-activation potentials
      for the sodium current, accompanied by a slowing of the rate of inactivation to
      half of the experimentally observed values. This suggests that once-only spiking
      can be attributed to the steady-state values of activation and inactivation of
      the sodium current, along with a slower rate of inactivation. Mapping of the
      resultant firing properties against steady-state and kinetic ion channel
      parameters revealed a high safety factor for once-only firing and showed that the
      time constant of inactivation of the sodium current was the key determinant of
      once-only or repetitive firing. The rapidly inactivating potassium current does
      not influence once-only firing or the maximum rate of firing in response to
      periodic excitation in these simulations. Although a contribution of other
      currents to produce once-only firing has not been excluded, this model suggests
      that the properties of the sodium current are sufficient to account for once-only
      firing.

PMID- 16081605
TI  - Spike firing allometry in avian intrapulmonary chemoreceptors: matching neural
      code to body size.
AB  - Biological rates in small animals are usually higher than those in large animals,
      yet the maximal rate of action potential (spike) generation in sensory neurons
      encoding rate functions is similar in all animals, due to the conserved genetics
      of voltage-gated ion channels. Therefore, sensory signals that vary at rates
      approaching maximal spike generation rate, as might occur in animals of
      diminished body size, may require specialized spike coding to convey this
      information. To test whether spike coding scales allometrically in sensory
      neurons monitoring signals that change frequency with body size, we recorded
      action potentials from 70 avian intrapulmonary chemoreceptors (IPC), respiratory
      neurons that detect lung CO2 changes during breathing, in five different avian
      species ranging in size from body mass Mb=0.045 kg (lovebirds) to 5.23 kg
      (geese). Since breathing frequency scales approximately to Mb-1/4 (higher in
      small birds, lower in large birds), we reasoned that IPC discharge frequencies
      may also scale to maintain spike information transmission within each breath. We
      found that phasic action potential discharge pattern, as quantified by the peak
      discharge rate and the magnitude of spike frequency adaptation, scaled between Mb
      0.22 and Mb-0.26, like breathing rate (P<0.05). Previously published values of
      peak discharge rate in IPC also fit this allometric relationship. We suggest that
      mass-dependent scaling of neural coding may be necessary for preserving
      information transmission with decreasing body size.

PMID- 16081606
TI  - The aerodynamic effects of wing-wing interaction in flapping insect wings.
AB  - We employed a dynamically scaled mechanical model of the small fruit fly
      Drosophila melanogaster (Reynolds number 100-200) to investigate force
      enhancement due to contralateral wing interactions during stroke reversal (the
      ;clap-and-fling'). The results suggest that lift enhancement during clap-and
      fling requires an angular separation between the two wings of no more than 10-12
      degrees . Within the limitations of the robotic apparatus, the clap-and-fling
      augmented total lift production by up to 17%, but depended strongly on stroke
      kinematics. The time course of the interaction between the wings was quite
      complex. For example, wing interaction attenuated total force during the initial
      part of the wing clap, but slightly enhanced force at the end of the clap phase.
      We measured two temporally transient peaks of both lift and drag enhancement
      during the fling phase: a prominent peak during the initial phase of the fling
      motion, which accounts for most of the benefit in lift production, and a smaller
      peak of force enhancement at the end fling when the wings started to move apart.
      A detailed digital particle image velocimetry (DPIV) analysis during clap-and
      fling showed that the most obvious effect of the bilateral ;image' wing on flow
      occurs during the early phase of the fling, due to a strong fluid influx between
      the wings as they separate. The DPIV analysis revealed, moreover, that
      circulation induced by a leading edge vortex (LEV) during the early fling phase
      was smaller than predicted by inviscid two-dimensional analytical models, whereas
      circulation of LEV nearly matched the predictions of Weis-Fogh's inviscid model
      at late fling phase. In addition, the presence of the image wing presumably
      causes subtle modifications in both the wake capture and viscous forces.
      Collectively, these effects explain some of the changes in total force and lift
      production during the fling. Quite surprisingly, the effect of clap-and-fling is
      not restricted to the dorsal part of the stroke cycle but extends to the
      beginning of upstroke, suggesting that the presence of the image wing distorts
      the gross wake structure throughout the stroke cycle.

PMID- 16081607
TI  - Tracing heme in a living cell: hemoglobin degradation and heme traffic in digest
      cells of the cattle tick Boophilus microplus.
AB  - Heme is present in all cells, acting as a cofactor in essential metabolic
      pathways such as respiration and photosynthesis. Moreover, both heme and its
      degradation products, CO, iron and biliverdin, have been ascribed important
      signaling roles. However, limited knowledge is available on the intracellular
      pathways involved in the flux of heme between different cell compartments. The
      cattle tick Boophilus microplus ingests 100 times its own mass in blood. The
      digest cells of the midgut endocytose blood components and huge amounts of heme
      are released during hemoglobin digestion. Most of this heme is detoxified by
      accumulation into a specialized organelle, the hemosome. We followed the fate of
      hemoglobin and albumin in primary cultures of digest cells by incubation with
      hemoglobin and albumin labeled with rhodamine. Uptake of hemoglobin by digest
      cells was inhibited by unlabeled globin, suggesting the presence of receptor
      mediated endocytosis. After endocytosis, hemoglobin was observed inside large
      digestive vesicles. Albumin was exclusively associated with a population of small
      acidic vesicles, and an excess of unlabeled albumin did not inhibit its uptake.
      The intracellular pathway of the heme moiety of hemoglobin was specifically
      monitored using Palladium-mesoporphyrin IX (Pd-mP) as a fluorescent heme analog.
      When pulse and chase experiments were performed using digest cells incubated with
      Pd-mP bound to globin (Pd-mP-globin), strong yellow fluorescence was found in
      large digestive vesicles 4 h after the pulse. By 8 h, the emission of Pd-mP was
      red-shifted and more evident in the cytoplasm, and at 12 h most of the
      fluorescence was concentrated inside the hemosomes and had turned green. After 48
      h, the Pd-mP signal was exclusively found in hemosomes. In methanol, Pd-mP showed
      maximal emission at 550 nm, exhibiting a red-shift to 665 nm when bound to
      proteins in vitro. The red emission in the cytosol and at the boundary of
      hemosomes suggests the presence of heme-binding proteins, probably involved in
      transport of heme to the hemosome. The existence of an intracellular heme shuttle
      from the digestive vesicle to the hemosome acting as a detoxification mechanism
      should be regarded as a major adaptation of ticks to a blood-feeding way of life.
      To our knowledge, this is the first direct observation of intracellular transport
      of heme in a living eukaryotic cell. A similar approach, using Pd-mP
      fluorescence, could be applied to study heme intracellular metabolism in other
      cell types.

PMID- 16081608
TI  - Shaken, not stirred: a serendipitous study of ants and earthquakes.
AB  - There is anecdotal evidence for profound behavioral changes prior to and during
      earthquakes in many organisms, including arthropods such as ants. Behavioral or
      physiological analysis has often, in light of these reports, been proposed as a
      means of earthquake prediction. We report here a serendipitous study of the
      effect of the powerful Landers earthquake in the Mojave Desert, USA (Richter
      magnitude 7.4) on ant trail dynamics and aerobic catabolism in the desert
      harvester ant Messor pergandei. We monitored trail traffic rates to and from the
      colony, trail speed, worker mass distributions, rates of aerobic catabolism and
      temperature at ant height before and during the earthquake, and for 3 days after
      the earthquake. Contrary to anecdotal reports of earthquake effects on ant
      behavior, the Landers earthquake had no effect on any measured aspect of the
      physiology or behavior of M. pergandei. We conclude that anecdotal accounts of
      the effects of earthquakes or their precursors on insect behavior should be
      interpreted with caution.

PMID- 16081609
TI  - Cardiorespiratory adjustments of homing pigeons to steady wind tunnel flight.
AB  - We made detailed cardiorespiratory measurements from homing pigeons during quiet
      rest and steady wind tunnel flight. Our pigeons satisfied their 17.4-fold
      increase in oxygen consumption during flight with a 7.4-fold increase in cardiac
      output (Q) and a 2.4-fold increase in blood oxygen extraction. Q was increased
      primarily by increasing heart rate sixfold. Comparisons between our study and
      those from the only other detailed cardiorespiratory study on flying birds reveal
      a number of similarities and important differences. Although the avian allometric
      equations from this earlier study accurately predicted the flight Q of our
      pigeons, this was primarily due to due to compensating discrepancies in their
      heart rate and stroke volume predictions. Additionally, the measured heart mass
      (MH)-specific Q (Q/MH) of our pigeons during wind tunnel flight was about 22%
      lower than the estimated value. Compared to running mammals in previous studies,
      the 1.65-fold Q of our pigeons is consistent with their larger heart mass.

PMID- 16081610
TI  - Ontogenetic changes in the response properties of individual, primary auditory
      afferents in the vocal plainfin midshipman fish Porichthys notatus Girard.
AB  - The auditory system of adult midshipman fish Porichthys notatus Girard is an
      important sensory receiver system used during intraspecific social communication
      to encode conspecific vocalizations, but the response properties and function of
      this system in the pre-adult stages are unknown. Midshipman fish, like other
      teleosts, use the saccule as the main acoustic end organ of the inner ear. In
      this study, we examined the discharge properties and the frequency response
      dynamics of auditory saccular afferent neurons in pre-adult midshipman
      (approximately 4-12 months of age) to determine whether encoding of auditory
      information, inclusive of conspecific vocalizations, changes across life history
      stages. Extracellular single unit recordings were made from saccular afferents
      while sound was presented via an underwater speaker. Comparisons with adult data
      show that the resting discharge rate and auditory threshold sensitivity increased
      with age/size, while temporal encoding of frequency did not show any significant
      shifts. The results indicate that the saccular afferents of juveniles, like those
      of non-reproductive adults, are best adapted to temporally encode the low
      frequency components (<or=100 Hz) of midshipman vocalizations. This report
      represents the first in vivo investigation of age-related changes in the encoding
      properties of individual auditory neurons for any fish species.

PMID- 16081611
TI  - Two-dimensional gel analysis of the heat-shock response in marine snails (genus
      Tegula): interspecific variation in protein expression and acclimation ability.
AB  - The degree to which temperature acclimation modifies the acute synthesis of the
      entire heat-shock protein (Hsp) complement is still unknown, but it may
      constitute an important mechanism for understanding the differences in
      acclimation ability among closely related ectothermic species that occupy widely
      varying thermal environments. In general, eurythermal (heat-tolerant) species
      modify physiological function in response to an increase in acclimation
      temperature to a greater extent than stenothermal (heat-sensitive) species. In
      the present work I used 35S-labelled amino acids and two-dimensional gel
      electrophoresis to test this assumption for how acclimation affects acute Hsp
      expression (referred to as phenotypic plasticity) in two heat-sensitive, low
      intertidal to subtidal zone turban snails, Tegula brunnea and T. montereyi, in
      comparison to a heat-tolerant, mid- to low-intertidal zone congener, T.
      funebralis. I was able (i) to detect the synthesis of over 30 proteins in gill
      tissue, primarily in the 70 kDa range, in response to an increase in temperature
      (13 degrees C, 24 degrees C, 27 degrees C and 30 degrees C), (ii) to assess the
      effect of acclimation (13 degrees C vs 22 degrees C) on acute Hsp synthesis, and
      (iii) to compare this effect among the three Tegula congeners. After increasing
      acclimation temperature from 13 degrees C to 22 degrees C, synthesis of the most
      highly expressed Hsps decreased more in T. brunnea and T. montereyi than in T.
      funebralis. Two highly expressed proteins of molecular mass 71 and 74 kDa,
      however, were also synthesized constitutively at 13 degrees C and changed with
      increasing acclimation temperature in all three species. Although similar in
      phenotypic plasticity, T. brunnea and T. montereyi synthesized either a 76 or a
      72 kDa cluster of proteins, respectively, and differed in how acclimation
      affected the acute synthesis of several 77 kDa proteins. Thus, in Tegula, the
      effect of acclimation on Hsp expression is (i) Hsp-specific, (ii) dependent on a
      protein's expression pattern (constitutive and inducible vs only inducible),
      (iii) and is actually limited in the more eurythermal mid- to low-intertidal
      congener. These results contradict the general assumption that greater heat
      tolerance correlates with an increased ability to modify physiological function
      in response to acclimation.

PMID- 16081612
TI  - Geometry of elytra opening and closing in some beetles (Coleoptera, Polyphaga).
AB  - Elytra in beetles move actively, driven by their own muscles, only during
      transient opening and closing. The kinematics of these movements have been
      inadequately described, sometimes controversially. Our goal was a quantitative 3
      D description of diverse active movements of the elytra, in terms of directions
      of the axes of elytra rotation. Broad opening and closing was video recorded in
      beetles, tethered by the mesothorax, and has been analyzed frame by frame. For
      tracing, small dots or straw arms were glued to the elytra. Opening and closing
      traces coincided. The trace of the elytron apex was a flat circular arc about the
      axis of abduction-adduction (AAA). The rising hemiaxis pointed contralaterad. The
      AAA was tilted forwards in Melolontha hippocastani, Allomyrina dichotoma and
      Prionus coriarius but backwards in Chalcophora mariana. In Cetonia aurata, the
      AAA had a low elevation and a strong backward orientation. If another elytra
      fixed point was traced in addition to the apex (in M. hippocastani and P.
      coriarius), then secondary rotation about the sutural edge (supination on
      opening) occurred. Modeling of abduction-adduction revealed that the elytron rose
      on opening if the AAA pointed contralaterad. The more the AAA was tilted forward,
      the more negative was the attack angle of the open elytra. The negative attack
      angle was partly compensated by positive body pitch and, more effectively, by
      supination of the costal edge about the sutural edge. The initial stage of
      opening included elevation of closed elytra (by 10-12 degrees) and partition to
      the sides, combined with an inward turn (<2-3 degrees). Axis of rotation at this
      stage presumably coincided with the AAA. Movement of one elytron with respect to
      the opposite one at the beginning of opening followed the shallow arc convex
      down. The geometry of this relative movement describes the initial partition of
      the elytra and release of the sutural lock.

PMID- 16081613
TI  - Cost of transport is increased after cold exposure in Monodelphis domestica:
      training for inefficiency.
AB  - Monodelphis domestica (Didelphidae: Marsupialia) lacks brown adipose tissue and
      thus relies on skeletal muscle as its primary thermogenic organ. Following cold
      exposure, the aerobic capacity of skeletal muscle in these animals is greatly
      increased. We investigated the effects of this plastic response to thermogenesis
      on locomotion and muscle mechanics. In cold-exposed animals, cost of transport
      was 15% higher than in controls but was unaffected by exercise training. Twitch
      kinetics in isolated semitendinosus muscles of cold-exposed animals were
      characteristic of slow-oxidative fiber types. Both time-to-peak tension and half
      relaxation time were longer and maximal shortening velocity was slower following
      cold exposure compared to either thermoneutral controls or exercise-trained
      animals. Further, muscles from the cold-exposed animals had greater fatigue
      resistance than either control or exercise-trained animals, indicating greater
      oxidative capacity. Finally, we identified an uncoupling protein 3 homologue,
      whose gene expression was upregulated in skeletal muscle of cold-exposed
      Monodelphis domestica. Cold exposure provided a potent stimulus for muscle
      plasticity, driving a fast-to-slow transition more effectively than exercise
      training. However, linked to the dramatic shift in muscle properties is an
      equally dramatic increase in whole animal muscle energetics during locomotion,
      suggesting an uncoupled state, or 'training for inefficiency'.

PMID- 16081614
TI  - Patterns of variation in glycogen, free glucose and lactate in organs of
      supercooled hatchling painted turtles (Chrysemys picta).
AB  - Hatchling painted turtles (Chrysemys picta) typically spend their first winter of
      life in a shallow, subterranean hibernaculum (the natal nest), where they may be
      exposed for extended periods to ice and cold. The key to their survival seems to
      be to avoid freezing and to sustain a state of supercooling. As temperature
      declines below 0 degrees C, however, the heart of an unfrozen turtle beats
      progressively slower, the diminished perfusion of peripheral tissues with blood
      induces a functional hypoxia, and anaerobic glycolysis assumes ever greater
      importance as a source of ATP. We hypothesized that diminished circulatory
      function in supercooled turtles also reduces the delivery of metabolic substrates
      to peripheral tissues from central stores in the liver, so that the tissues
      depend increasingly on endogenous stores to fuel their metabolism. We discovered
      in the current investigation that part of the glycogen reserve in hearts and
      brains of hatchlings is mobilized during the first 10 days of exposure to -6
      degrees C but that glucose from hepatic glycogen supports metabolism of the
      organs thereafter. Hatchlings that were held at -6 degrees C for 10 days and then
      at +3 degrees C for another 10 days were able to reconstitute some of the reserve
      of glycogen in heart and liver but not the glycogen reserve in brain. Patterns of
      accumulation of lactate in individual organs were very similar to those reported
      for whole animals in a companion study, and point to a high degree of reliance on
      anaerobic metabolism at -6 degrees C and to a lesser degree of reliance on
      anaerobiosis at higher subzero temperatures. Lactate had returned to baseline
      levels in organs of animals that were held for 10 days at -6 degrees C and for
      another 10 days at +3 degrees C, but free glucose remained elevated. Indeed,
      carbohydrate metabolism probably does not return to the pre-exposure state in any
      of the major organs until well after the exposure to subzero temperatures has
      ended, circulatory sufficiency has been restored, and aerobic respiration has
      fully supplanted anaerobic respiration as a source of ATP.

PMID- 16081615
TI  - Three calpains and ecdysone receptor in the land crab Gecarcinus lateralis:
      sequences, expression and effects of elevated ecdysteroid induced by eyestalk
      ablation.
AB  - Crustacean muscle has four calpain-like proteinase activities (CDP I, IIa, IIb
      and III) that are involved in molt-induced claw muscle atrophy, as they degrade
      myofibrillar proteins in vitro and in situ. Using PCR cloning techniques, three
      full-length calpain cDNAs (Gl-CalpB, Gl-CalpM and Gl-CalpT) were isolated from
      limb regenerates of the tropical land crab Gecarcinus lateralis. All three had
      highly conserved catalytic (dII) and C2-like (dIII) domains. Gl-CalpB was
      classified as a typical, or EF-hand, calpain, as the deduced amino acid sequence
      had a calmodulin-like domain IV in the C-terminus and was most similar to
      Drosophila calpains A and B. Based on its estimated mass (approximately 88.9 kDa)
      and cross-immunoreactivity with a polyclonal antibody raised against Dm-CalpA, Gl
      CalpB may encode CDP IIb, which is a homodimer of a 95-kDa subunit. It was
      expressed in all tissues examined, including skeletal muscle, heart, integument,
      gill, digestive gland, hindgut, nerve ganglia, gonads and Y-organ (molting
      gland). Both Gl-CalpM and Gl-CalpT were classified as atypical, or non-EF-hand,
      calpains, as they lacked a domain IV sequence. Gl-CalpM was a homolog of Ha-CalpM
      from lobster, based on similarities in deduced amino acid sequence, estimated
      mass (approximately 65.2 kDa) and structural organization (both were truncated at
      the C-terminal end of dIII). It was expressed at varying levels in most tissues,
      except Y-organ. Gl-CalpT (approximately 74.6 kDa) was similar to TRA-3 in the
      nematode Caenorhabditis elegans; domain IV was replaced by a unique ;T domain'
      sequence. It was expressed in most tissues, except eyestalk ganglia and Y-organ.
      The effects of elevated ecdysteroid, induced by eyestalk ablation, on calpain and
      ecdysone receptor (Gl-EcR) mRNA levels in skeletal muscles were quantified by
      real-time PCR. At 1 day after eyestalk ablation, Gl-EcR and Gl-CalpT mRNA levels
      increased 15- and 19.3-fold, respectively, in claw muscle but not in thoracic
      muscle. At 3 days after eyestalk ablation, Gl-EcR and Gl-CalpT mRNA levels in
      claw muscle had decreased to 2.8-fold and 4.3-fold higher than those in intact
      controls, respectively, suggesting a feedback inhibition by ecdysteroid. There
      was no significant effect of eyestalk ablation on Gl-CalpB and Gl-CalpM mRNA
      levels. Gl-CalpT and Gl-EcR mRNA levels were significantly correlated in both
      claw and thoracic muscles from intact and eyestalk-ablated animals. The data
      suggest that Gl-CalpT is involved in initiation of claw muscle atrophy by
      ecdysteroids. Premolt reduction in claw muscle mass and concomitant remodeling of
      the sarcomere probably result from post-transcriptional regulation of calpains.

PMID- 16081616
TI  - Influence of host size on the clutch size and developmental success of the
      gregarious ectoparasitoid Eulophus pennicornis (Nees) (Hymenoptera: Eulophidae)
      [corrected] attacking larvae of the tomato moth Lacanobia oleracea (L.)
      (Lepidoptera: Noctuidae).
AB  - The relationship between clutch size, host size and progeny survival in the
      gregarious ectoparasitoid Eulophus pennicornis was investigated in a number of
      scenarios. When naive parasitoids were exposed singly to Lacanobia oleracea
      hosts, clutch size was strongly correlated with the size of the host. However,
      survival of parasitoid offspring was negatively affected by the size of the host
      such that, in larger hosts, greater wasp larval and pupal mortality was recorded.
      As a result, no gain in realised fecundity was achieved through parasitizing L.
      oleracea larvae of mass >0.4 g over hosts of mass between 0.2-0.3 g. When exposed
      to populations of mixed stadium hosts (larvae in the fourth, fifth and sixth
      instars) during the entire lifespan of the wasp, host size and clutch size were
      correlated in early ovipositions (first three ovipositions). However, as the
      wasps aged, the relationship was much less apparent. When the parasitoid was
      restricted to foraging upon populations of sixth instar hosts only, no
      relationship between host size and clutch size was apparent. Exposure of the
      parasitoid to mixed and fixed stadium host populations showed that final (sixth)
      stadium hosts were the most frequently parasitized (ca. 96% of parasitized hosts)
      and that the average numbers of eggs laid per wasp, and the number of hosts
      parasitized, was significantly lower when the parasitoid was provided with fourth
      or fifth instar hosts only. The results indicate that the reproductive success of
      E. pennicornis does not increase with increasing host size or greater resource
      availability above a certain threshold, and that the physiological status of the
      host at the time of parasitism is the governing factor determining oviposition
      decisions and parasitoid survival. We conclude that E. pennicornis has been
      selected to preferentially utilize those hosts that maximize progeny survival and
      to adapt clutch size to the size of such hosts. We hypothesize that the major
      driver leading to the evolution of this strategy is the ability of the parasitoid
      to physiologically regulate the host.

PMID- 16081617
TI  - A chemotactic response facilitates mosquito salivary gland infection by malaria
      sporozoites.
AB  - Sporozoite invasion of mosquito salivary glands is critical for malaria
      transmission to vertebrate hosts. After release into the mosquito hemocoel, the
      means by which malaria sporozoites locate the salivary glands is unknown. We
      developed a Matrigel-based in vitro system to observe and analyze the motility of
      GFP-expressing Plasmodium berghei sporozoites in the presence of salivary gland
      products of Anopheles stephensi mosquitoes using temperature-controlled, low
      light-level video microscopy. Sporozoites moved toward unheated salivary gland
      homogenate (SGH) but not to SGH that had been heated at 56 degrees C for 30 min.
      We also investigated the origin of the attracted population. Attraction to SGH
      was restricted to hemolymph- and oocyst-derived sporozoites; salivary gland
      derived sporozoites were not attracted to SGH. These data imply that sporozoites
      employ a chemotactic response to high molecular mass proteins or carbohydrate
      binding proteins to locate salivary glands. This raises the possibility of
      utilizing anti-chemotactic factors for the development of mosquito transmission
      blocking agents.

PMID- 16081618
TI  - External compression increases forearm perfusion.
AB  - Application of compression stockings to the lower extremities is a widely used
      therapeutic intervention to improve venous return, but there is little
      information about the effects of compression on local arterial perfusion.
      Therefore, we tested the hypothesis that a positive external pressure increases
      forearm perfusion. The relation of increasing external pressure induced by
      standardized compression to the arterial inflow and arterial flow reserve of the
      forearm was critically evaluated in a group of healthy young men (n = 9). Flow
      was measured with venous occlusion plethysmography after a 10-min application of
      six different stockings with compression pressure increasing from 13 to 23 mmHg.
      During compression, the arterial inflow increased significantly from 3.7 +/- 0.85
      to 8.8 +/- 2.01 ml.min(-1).100 ml tissue(-1) (P < 0.001) and the arterial flow
      reserve increased from 17.7 +/- 4.7 to 28.3 +/- 7.0 ml.min(-1).100 ml tissue(-1).
      The flow increase was persistent after 3 h of constant application of external
      pressure and also during simultaneous low-intensity hand grip. Similar results
      obtained with occlusion plethysmography were seen with MRI. During the
      interventions, forearm temperature was unchanged, and the volunteers reported no
      discomfort. In conclusion, 1) arterial perfusion of the human forearm increases
      more than twofold during application of external compression over a pressure
      range of 13-23 mmHg, and 2) the result is interpreted as an autoregulatory
      response following the decrease of the vascular transmural pressure gradient.

PMID- 16081619
TI  - Prolonged electrical muscle stimulation exercise improves strength and aerobic
      capacity in healthy sedentary adults.
AB  - This investigation evaluated training responses to prolonged electrical muscle
      stimulation (EMS) in sedentary adults. Fifteen healthy subjects (10 men, 5 women)
      with a sedentary lifestyle completed a 6-wk training program during which they
      completed an average of 29 1-h EMS sessions. The form of EMS used by the subjects
      was capable of eliciting a cardiovascular exercise response without loading the
      limbs or joints. It achieved this by means of inducing rapid, rhythmical
      contractions in the large leg muscles. A crossover study design was employed with
      subjects undergoing their habitual activity levels during the nontraining phase
      of the study. The training effect was evaluated by means of a treadmill test to
      determine peak aerobic capacity [peak oxygen consumption (Vo(2))], a 6-min
      walking distance test, and measurement of body mass index (BMI) and quadriceps
      muscle strength. At baseline, the mean values for peak Vo(2), 6-min walking
      distance, quadriceps strength, and BMI were 2.46 +/- 0.57 l/min, 493.3 +/- 36.8
      m, 360.8 +/- 108.7 N, and 26.9 +/- 3.4 kg/m(2), respectively. After training,
      subjects demonstrated statistically significant improvements in all variables
      except BMI. Peak Vo(2) increased by an average of 0.24 +/- 0.16 l/min (P < 0.05),
      walking distance increased by 36.6 +/- 19.7 m (P < 0.005), and quadriceps
      strength increased by 87.5 +/- 55.9 N (P < 0.005); we did not observe a
      significant effect due to training on BMI (P > 0.05). These results suggest that
      EMS can be used in sedentary adults to improve physical fitness. It may provide a
      viable alternative to more conventional forms of exercise in this population.

PMID- 16081620
TI  - Transcriptional profiling in mouse skeletal muscle following a single bout of
      voluntary running: evidence of increased cell proliferation.
AB  - Skeletal muscle undergoes adaptation following repetitive bouts of exercise. We
      hypothesize that transcriptional reprogramming and cellular remodeling start in
      the early phase of long-term training and play an important role in skeletal
      muscle adaptation. The aim of this study was to define the global mRNA expression
      in mouse plantaris muscle during (run for 3 and 12 h) and after (3, 6, 12, and 24
      h postexercise) a single bout of voluntary running and compare it with that after
      long-term training (4 wk of running). Among 15,832 gene elements surveyed in a
      high-density cDNA microarray analysis, 900 showed more than twofold changes at
      one or more time points. K-means clustering and cumulative hypergeometric
      probability distribution analyses revealed a significant enrichment of genes
      involved in defense, cell cycle, cell adhesion and motility, signal transduction,
      and apoptosis, with induced expression patterns sharing similar patterns with
      that of peroxisome proliferator activator receptor-gamma coactivator-1alpha and
      vascular endothelial growth factor A. We focused on the finding of a delayed (at
      24 h postexercise) induction of mRNA expression of cell cycle genes origin
      recognition complex 1, cyclin A2, and cell division 2 homolog A
      (Schizoccharomyces pombe) and confirmed increased cell proliferation by in vivo 5
      bromo-2'-deoxyuridine labeling following voluntary running. X-ray irradiation of
      the hindlimb significantly diminished exercise-induced 5-bromo-2'-deoxyuridine
      incorporation. These findings suggest that a single bout of voluntary running
      activates the transcriptional network and promotes adaptive processes in skeletal
      muscle, including cell proliferation.

PMID- 16081621
TI  - Role of matrix metalloproteinase-9 in endothelial apoptosis in chronic heart
      failure in mice.
AB  - Accumulation of oxidized extracellular matrix between endothelium and muscle is
      an important risk factor in the endothelium-myocytes uncoupling in congestive
      heart failure. Although ventricular remodeling is accompanied by increased matrix
      metalloproteinase (MMP)-9 activity, it is unclear whether MMP-9 plays a role in
      endothelial apoptosis in chronic volume overload congestive heart failure. We
      tested the hypothesis that, in chronic volume overload, myocardial dysfunction
      involves endocardial endothelial (EE) apoptosis in response to MMP-9 activation,
      extracellular matrix accumulation, and endothelium-myocytes uncoupling.
      Arteriovenous fistula (AVF) was created in control (FVB/NJ) and MMP-9 knockout
      (MMP-9KO; FVB.Cg-MMP9(tm1Tvu)/J) mice. Sham surgery was used as control. Mice
      were grouped as follows: wild type, n = 3 (sham control); MMP-9KO, n = 3 (sham);
      AVF, n = 3; and MMP-9KO + AVF (n = 3). Heart function was analyzed by M-mode and
      Doppler echocardiography, and with a pressure-tipped Millar catheter placed in
      the left ventricle of anesthetized mice 8 wk after AVF. Apoptosis was detected by
      measuring caspase-3, transferase-mediated dUTP nick-end labeling (TUNEL), and CD
      31 by immunolabeling. Protease-activated receptors-1, connexin-43, and a
      disintegrin and MMP-12 (ADAM-12) expression were measured by Western blot
      analyses. MMP-2 and MMP-9 expression were measured by quantitative RT-PCR.
      Compared with control, AVF caused an increase in left ventricle end diastolic
      pressure and decrease in -dP/dt. In contrast, in the MMP-9KO + AVF group, these
      variables were changed toward control levels. Increased EE apoptosis (caspase-3
      activation and TUNEL/CD-31 colabeling) in AVF mice was prevented in the MMP-9KO +
      AVF group. Protease-activated receptor-1, connexin-43, and ADAM-12 were induced
      in AVF. MMP-9 gene ablation ameliorated the induction. The results suggest that
      impaired cardiac function in volume overload is associated with EE apoptosis,
      cardiac remodeling, and endothelium-myocytes uncoupling in response to MMP-9
      activation.

PMID- 16081622
TI  - Identifying airways responsible for heterogeneous ventilation and mechanical
      dysfunction in asthma: an image functional modeling approach.
AB  - We present an image functional modeling approach, which synthesizes imaging and
      mechanical data with anatomically explicit computational models. This approach is
      utilized to identify the relative importance of small and large airways in the
      simultaneous deterioration of mechanical function and ventilation in asthma.
      Positron emission tomographic (PET) images provide the spatial distribution and
      relative extent of ventilation defects in asthmatic subjects
      postbronchoconstriction. We also measured lung resistance and elastance from 0.15
      to 8 Hz. The first step in image functional modeling involves mapping ventilation
      three-dimensional images to the computational model and identifying the largest
      sized airways of the model that, if selectively constricted, could precisely
      match the size and anatomic location of ventilation defects imaged by PET. In
      data from six asthmatic subjects, these airways had diameters <2.39 mm and mostly
      <0.44 mm. After isolating and effectively closing airways in the model associated
      with these ventilation defects, we imposed constriction with various means and
      standard deviations to the remaining airways to match the measured lung
      resistance and elastance from the same subject. Our results show that matching
      both the degree of mechanical impairment and the size and location of the PET
      ventilation defects requires either constriction of airways <2.4 mm alone, or a
      simultaneous constriction of small and large airways, but not just large airways
      alone. Also, whereas larger airway constriction may contribute to mechanical
      dysfunction during asthma, degradation in ventilation function requires
      heterogeneous distribution of near closures confined to small airways.

PMID- 16081623
TI  - Structural Achilles tendon properties in athletes subjected to different exercise
      modes and in Achilles tendon rupture patients.
AB  - The prevalence of Achilles tendon (AT) injury is high in various sports, and AT
      rupture patients have been reported to have a 200-fold risk of sustaining a
      contralateral rupture. Tendon adaptation to different exercise modes is not fully
      understood. The present study investigated the structural properties of the AT in
      male elite athletes that subject their AT to different exercise modes as well as
      in Achilles rupture patients. Magnetic resonance imaging of the foot and leg,
      anthropometric measurements, and maximal isometric plantar flexion force were
      obtained in 6 male AT rupture patients and 25 male elite athletes (kayak/control
      group n = 9, volleyball n = 8 and endurance running n = 8). AT cross-sectional
      area (CSA) was normalized to body mass. Runners had a larger normalized AT CSA
      along the entire length of the tendon compared with the control group (P < 0.05).
      The volleyball subjects had a larger normalized CSA compared with the control
      group (P < 0.05) in the area of thinnest tendon CSA. No structural differences of
      the AT were found in the rupture subjects compared with the control group.
      Rupture subjects did not subject their AT to greater force or stress during a
      maximal voluntary isometric plantar flexion than the other groups. The CSA of the
      triceps surae musculature was the strongest predictor of AT CSA (r(s) = 0.569, P
      < 0.001). This study is the first to show larger CSA in tendons that are
      subjected to intermittent high loads. AT rupture patients did not display
      differences in structural or loading properties of the tendons.

PMID- 16081624
TI  - Regional difference of blood flow in anesthetized rats during reduced gravity
      induced by parabolic flight.
AB  - To examine a hypothesis that change in regional blood flow due to decreased
      hydrostatic pressure gradient and redistribution of blood during reduced gravity
      (rG) is different between organs, changes in cerebrocortical blood flow (CBF) and
      blood flow in the temporal muscle (MBF) with exposure to rG were measured in
      anesthetized rats in head-up tilt and flat positions during parabolic flight.
      Carotid arterial pressure (CAP), jugular venous pressure (JVP), and abdominal
      aortic pressure were also measured simultaneously. In the head-up tilt group, CBF
      increased by 15 +/- 3% within 3 s of entry into rG and rapidly recovered during
      rG. MBF also increased, but the change was significantly greater than that of
      CBF. JVP increased by 1.8 +/- 0.5 mmHg, probably due to loss of hydrostatic
      pressure gradient, since the measuring point of JVP was 2-3 cm above the
      hydrostatic indifference point. CAP and abdominal aortic pressure increased by
      16.7 +/- 2 and 7.7 +/- 2 mmHg, respectively, compared with the 1-G condition.
      Muscle vascular resistance [(CAP-JVP)/MBF] decreased on entry into rG, but no
      significant change was observed in cerebrocortical vascular resistance [(CAP
      JVP)/CBF]. In the flat group, no significant change was observed in all the
      variables. The results indicate that arteriolar vasodilatation occurs in the
      temporal muscle but not in the cerebral cortex. Thus the blood flow control
      mechanism at the onset of rG is different between intra- and extracranial organs.

PMID- 16081625
TI  - Caffeine improves endurance in 75-yr-old citizens: a randomized, double-blind,
      placebo-controlled, crossover study.
AB  - This study investigated the effect of caffeine on physical performance in healthy
      citizens aged > or =70 yr. The randomized, double-blind, placebo-controlled,
      crossover study was conducted in 15 men and 15 women recruited by their general
      practitioner. Participants abstained from caffeine for 48 h and were randomized
      to receive one capsule of placebo and then caffeine (6 mg/kg) or caffeine and
      then placebo with 1 wk in between. One hour after intervention, we measured
      reaction and movement times, postural stability, walking speed, cycling at 65% of
      expected maximal heart rate, perceived effort during cycling, maximal isometric
      arm flexion strength, and endurance. Analysis was by intention to treat, and P <
      0.05 was regarded as significant. Caffeine increased cycling endurance by 25%
      [95% confidence interval (CI): 13-38; P = 0.0001] and isometric arm flexion
      endurance by 54% (95% CI: 29-83; P = 0.0001). Caffeine also reduced the rating of
      perceived exertion after 5 min of cycling by 11% (95% CI: 5-17; P = 0.002) and
      postural stability with eyes open by 25% (95% CI: 2-53; P = 0.03). Caffeine
      ingestion did not affect muscle strength, walking speed, reaction, and movement
      times. At the end of the study, 46% of participants correctly identified when
      they received caffeine and placebo. Caffeine increased exercise endurance in
      healthy citizens aged > or =70 yr, but the participants' reasons for stopping the
      test may have varied between subjects, as the cycling test was done at
      approximately 55% of maximal oxygen consumption. Further studies are required to
      investigate whether caffeine can be utilized to improve the physical performance
      of elderly citizens.

PMID- 16081626
TI  - Improved insulin action following short-term exercise training: role of energy
      and carbohydrate balance.
AB  - Short-term exercise training improves insulin action, but the impact of replacing
      the energy expended during exercise to prevent energy deficit is unclear. The
      purpose of this study was to establish the role of an energy deficit in mediating
      improved insulin action after short-term exercise training. Two groups of
      previously sedentary, overweight/obese subjects performed 6 consecutive days of
      moderate-intensity walking to expend approximately 500 kcal/day. In one group,
      energy and carbohydrate expended during exercise was replaced [balance group
      (BAL), n = 8] and in the other group, energy was not replaced [deficit group
      (DEF), n = 8]. Insulin action (blood glucose uptake during glucose infusion) and
      selected lipids and adipokines were measured pre- and posttraining. Training
      increased estimated daily energy expenditure by approximately 500 kcal/day (DEF =
      469 +/- 45, BAL = 521 +/- 48), generating an energy deficit in DEF (-481 +/- 24
      kcal/day) but not BAL (+8 +/- 20 kcal/day). Insulin action increased 40% in DEF
      (P = 0.032) but not BAL (-8.4%, P = 0.107). Hepatic glucose production was
      suppressed during glucose infusion in DEF (30.2 +/- 9.5%, P = 0.037) but not BAL
      (-10.0 +/- 7.4%, P = 0.417). Fasting leptin concentrations declined in DEF but
      not BAL. Six days of exercise training without energy replacement significantly
      increased insulin action. Restoring energy balance by refeeding the energy and
      carbohydrate expended during exercise resulted in no change in insulin action.
      These findings suggest that changes in short-term energy and/or carbohydrate
      balance play a key role in mediating the beneficial effects of exercise on whole
      body and hepatic insulin action.

PMID- 16081627
TI  - Dose response to rhCC10-augmented surfactant therapy in a lamb model of infant
      respiratory distress syndrome: physiological, inflammatory, and kinetic profiles.
AB  - While surfactant (SF) therapy alone improves respiratory distress syndrome (RDS)
      associated gas exchange and lung stability, absence of anti-inflammatory proteins
      limits efficacy with respect to inflammation. Clara cell secretory protein
      (CC10), deficient in preterm infants, prevents SF degradation and has anti
      inflammatory properties. In this study, intratracheal recombinant human (rh) CC10
      (Claragen)-augmented SF (Survanta, Ross) therapy was examined in a premature lamb
      model of RDS with respect to inflammation and kinetic dose-response profiles.
      Preterm lambs (n = 24; gestational age: 126 +/- 3 days) were delivered via
      cesarean section, sedated, ventilated, and randomized into groups: 100 mg/kg SF,
      100 mg/kg SF followed by 0.5 mg/kg rhCC10, 100 mg/kg SF followed by 1.5 mg/kg
      rhCC10, and 100 mg/kg SF followed by 5.0 mg/kg rhCC10. Arterial blood chemistry
      and lung mechanics were monitored; lungs were lavaged and snap-frozen after 4 h.
      TNF-alpha, IL-8 in plasma; TNF-alpha, IL-6, IL-8, myeloperoxidase in lung; and
      rhCC10 in plasma, urine, bronchoalveolar lavage, and lung were analyzed.
      Improvement in compliance, peak inspiratory pressure, and ventilatory efficiency
      index were greatest (P < 0.05) with SF + 5.0 mg/kg rhCC10. Plasma, urine,
      bronchoalveolar lavage, and lung [rhCC10] (where brackets denote concentration)
      increased (P < 0.01) with dose. Plasma [IL-8] was lower (P < 0.05) with rhCC10
      than SF alone. Treatment with at least 1.5 mg/kg rhCC10 resulted in lower (P <
      0.05) lung [TNF-alpha], [IL-8], and [myeloperoxidase]; SF + 1.5 mg/kg rhCC10
      group had lower (P < 0.05) lung [IL-6], compared with all other groups. Compared
      with SF alone, SF augmented with at least 1.5 mg/kg rhCC10 decreased RDS-induced
      lung and systemic inflammation. Given that inflammation may lead to functional
      compromise, these data suggest that early intervention with rhCC10 may enhance SF
      therapy and warrant longer duration studies to determine its role to decrease
      long-term complications of ventilator management.

PMID- 16081628
TI  - Length adaptation of airway smooth muscle: a stochastic model of cytoskeletal
      dynamics.
AB  - To account for cytoskeleton remodeling as well as smooth muscle length
      adaptation, here we represent the cytoskeleton as a two-dimensional network of
      links (contractile filaments or stress fibers) that connect nodes (dense plaques
      or focal adhesions). The network evolves in continuous turnover with
      probabilities of link formation and dissolution. The probability of link
      formation increases with the available fraction of contractile units, increases
      with the degree of network activation, and decreases with increasing distance
      between nodes, d, as 1/d(s), where s controls the distribution of link lengths.
      The probability of link dissolution decays with time to mimic progressive
      cytoskeleton stabilization. We computed network force (F) as the vector summation
      of link forces exerted at all nodes, unloaded shortening velocity (V) as being
      proportional to the average link length, and network compliance (C) as the change
      in network length per change in elastic force. Imposed deformation caused F to
      decrease transiently and then recover dynamically; recovery ability decreased
      with increasing time after activation, mimicking observed biological behavior.
      Isometric contractions showed small sensitivity of F to network length, thus
      maintaining high force over a wide range of lengths; V and C increased with
      increasing length. In these behaviors, link length regulation, as described by
      the parameter s, was found to be crucial. Concerning length adaptation, all
      phenomena reported thus far in the literature were captured by this extremely
      simple network model.

PMID- 16081629
TI  - Detection of functionally active melanocortin receptors and evidence for an
      immunoregulatory activity of alpha-melanocyte-stimulating hormone in human dermal
      papilla cells.
AB  - Proopiomelanocortin (POMC)-derived peptides and their receptors have been
      identified in many peripheral organs including the skin in which they exert a
      diversity of biological actions. We investigated the expression and potential
      role of the POMC system in human dermal papilla cells (DPCs), a specialized
      cutaneous mesenchymal cell type regulating hair follicle activity. In culture,
      these cells expressed POMC and displayed immunoreactivity for ACTH, alphaMSH, and
      beta-endorphin. Among the prohormone convertases (PCs) tested, only PC2, its
      chaperone 7B2, and furin convertase but not PC1 and paired basic amino acid
      cleaving enzyme 4 gene were detected. Human DPCs in vitro expressed both the
      melanocortin-1 receptor (MC-1R) and MC-4R, and immunoreactivity for these
      receptors was also present in cells of the human dermal papilla in situ. In
      contrast to the dermal papilla of agouti mice, agouti signaling protein, a
      natural and highly selective MC-1R and MC-4R antagonist, was undetectable in
      human DPCs. The MC-Rs detected in human DPCs were functionally active because
      alphaMSH increased intracellular cAMP and calcium. Preincubation of the cells
      with a synthetic peptide corresponding to the C-terminal domain of agouti
      signaling protein abrogated cAMP induction by alphaMSH. Furthermore, alphaMSH was
      capable of antagonizing the expression of intercellular adhesion molecule-1
      induced by the proinflammatory cytokine interferon-gamma. Our data suggest a
      regulatory function of alphaMSH within the dermal papilla whose disruption may
      lead to deregulation of immune and inflammatory responses of the hair follicle,
      thereby possibly contributing to the development of inflammatory forms of
      alopecia.

PMID- 16081630
TI  - Betacellulin-delta4, a novel differentiation factor for pancreatic beta-cells,
      ameliorates glucose intolerance in streptozotocin-treated rats.
AB  - We previously described a novel alternatively spliced mRNA transcript of the
      betacellulin (BTC) gene. This splice isoform, termed BTC-delta4, lacks the C-loop
      of the epidermal growth factor motif and the transmembrane domain as a result of
      exon 4 'skipping'. In this study, we expressed BTC-delta4 recombinantly to
      explore its biological function. When BTC-delta4 was expressed in COS-7 cells, it
      was secreted largely into the culture medium, in contrast to BTC. Unlike BTC,
      highly purified recombinant BTC-delta4 produced in Escherichia coli failed to
      bind or induce tyrosine phosphorylation of either ErbB1 or ErbB4, nor did it
      antagonize the binding of BTC to these receptors. Consistent with this, BTC
      delta4 failed to stimulate DNA synthesis in Balb/c 3T3 and INS-1 cells. However,
      BTC-delta4 induced differentiation of pancreatic beta-cells; BTC-delta4 converted
      AR42J cells to insulin-producing cells. When recombinant BTC-delta4 was
      administered to streptozotocin-treated neonatal rats, it reduced the plasma
      glucose concentration and improved glucose tolerance. Importantly, BTC-delta4
      significantly increased the insulin content, the beta-cell mass, and the numbers
      of islet-like cell clusters and PDX-1-positive ductal cells. Thus, BTC-delta4 is
      a secreted protein that stimulates differentiation of beta-cells in vitro and in
      vivo in an apparent ErbB1- and ErbB4-independent manner. The mechanism by which
      BTC-delta4 exerts this action on beta-cells remains to be defined but presumably
      involves an, as yet, unidentified unique receptor.

PMID- 16081631
TI  - A positive feedback loop that regulates cyclooxygenase-2 expression and
      prostaglandin F2alpha synthesis via the F-series-prostanoid receptor and
      extracellular signal-regulated kinase 1/2 signaling pathway.
AB  - Cyclooxygenase (COX) enzymes catalyze the biosynthesis of eicosanoids, including
      prostaglandin (PG) F2alpha. PGF2alpha exerts its autocrine/paracrine function by
      coupling to its G protein-coupled receptor [F-series-prostanoid (FP) receptor] to
      initiate cell signaling and target gene transcription. In the present study, we
      found elevated expression of COX-2 and FP receptor colocalized together within
      the neoplastic epithelial cells of endometrial adenocarcinomas. We investigated a
      role for PGF2alpha-FP receptor interaction in modulating COX-2 expression and
      PGF2alpha biosynthesis using an endometrial adenocarcinoma cell line stably
      transfected with the FP receptor cDNA (FPS cells). PGF2alpha-FP receptor
      activation rapidly induced COX-2 promoter, mRNA, and protein expression in FPS
      cells. These effects of PGF2alpha on the expression of COX-2 could be abolished
      by treatment of FPS cells with an FP receptor antagonist (AL8810) and chemical
      inhibitor of ERK1/2 kinase (PD98059), or by inactivation of ERK1/2 signaling with
      dominant-negative mutant isoforms of Ras or ERK1/2 kinase. We further confirmed
      that elevated COX-2 protein in FPS cells could biosynthesize PGF2alpha de novo to
      promote a positive feedback loop to facilitate endometrial tumorigenesis.
      Finally, we have shown that PGF2alpha could potentiate tumorigenesis in
      endometrial adenocarcinoma explants by inducing the expression of COX-2 mRNA.

PMID- 16081632
TI  - Glucose stimulates glucagon release in single rat alpha-cells by mechanisms that
      mirror the stimulus-secretion coupling in beta-cells.
AB  - In isolated rat pancreatic alpha-cells, glucose, arginine, and the sulfonylurea
      tolbutamide stimulated glucagon release. The effect of glucose was abolished by
      the KATP-channel opener diazoxide as well as by mannoheptulose and azide,
      inhibitors of glycolysis and mitochondrial metabolism. Glucose inhibited KATP
      channel activity by 30% (P<0.05; n=5) and doubled the free cytoplasmic Ca2+
      concentration. In cell-attached recordings, azide opened KATP channels. The N
      type Ca2+-channel blocker omega-conotoxin and the Na+-channel blocker
      tetrodotoxin inhibited glucose-induced glucagon release whereas
      tetraethylammonium, a blocker of delayed rectifying K+ channels, increased
      secretion. Glucagon release increased monotonically with increasing K+
      concentrations. omega-Conotoxin suppressed glucagon release to 15 mM K+, whereas
      a combination of omega-conotoxin and an L-type Ca2+-channel inhibitor was
      required to abrogate secretion in 50 mM K+. Recordings of cell capacitance
      revealed that glucose increased the exocytotic response evoked by membrane
      depolarization 3-fold. This correlated with a doubling of glucagon secretion by
      glucose in intact rat islets exposed to diazoxide and high K+. In whole-cell
      experiments, exocytosis was stimulated by reducing the cytoplasmic ADP
      concentration, whereas changes of the ATP concentration in the physiological
      range had little effect. We conclude that glucose stimulates glucagon release
      from isolated rat alpha-cells by KATP-channel closure and stimulation of Ca2+
      influx through N-type Ca2+ channels. Glucose also stimulated exocytosis by an
      amplifying mechanism, probably involving changes in adenine nucleotides. The
      stimulatory action of glucose in isolated alpha-cells contrasts with the
      suppressive effect of the sugar in intact islets and highlights the primary
      importance of islet paracrine signaling in the regulation of glucagon release.

PMID- 16081633
TI  - Relationship between thyroid peroxidase T cell epitope restriction and antibody
      recognition of the autoantibody immunodominant region in human leukocyte antigen
      DR3 transgenic mice.
AB  - We investigated the relationship between thyroid peroxidase (TPO) antibody and T
      lymphocyte epitopes in TPO-adenovirus (TPO-Ad) immunized BALB/c mice and mice
      transgenic for the human class II molecule DR3 associated with human thyroid
      autoimmunity. TPO autoantibodies are largely restricted to an immunodominant
      region (IDR). BALB/c mice immunized with fewer (10(7) vs. 10(9)) TPO-Ad particles
      developed TPO antibodies with lower titers that displayed greater restriction to
      the IDR. However, as with higher-dose TPO-Ad immunization, T cell epitopes
      (assessed by splenocyte interferon-gamma response to TPO in vitro) were highly
      diverse and variable in different animals. In contrast, DR3 mice immunized the
      higher TPO-Ad dose (10(9) particles) had high TPO antibody levels that showed
      relative focus on the IDR. Moreover, T cell epitopes recognized by splenocytes
      from DR3 mice showed greater restriction than BALB/c mice. Antibody affinities
      for TPO were higher in DR3 than in BALB/c mice. The present study indicates that
      weak TPO-Ad immunization of BALB/c mice (with consequent low TPO antibody titers)
      is required for enhanced IDR focus yet is not associated with T cell epitopic
      restriction. Humanized DR3 transgenic mice, despite stronger TPO-Ad immunization,
      develop higher titer TPO antibodies that do focus on the autoantibody IDR with T
      cells that recognize a more limited range of TPO peptides. These data suggest a
      relationship between major histocompatibility complex class II molecules and the
      development of antibodies to the IDR, a feature of human thyroid autoimmunity.

PMID- 16081634
TI  - Somatostatin increases voltage-gated K+ currents in GH3 cells through activation
      of multiple somatostatin receptors.
AB  - The secretion of GH by somatotropes is inhibited by somatostatin (SRIF) through
      five specific membrane receptors (SSTRs). SRIF increases both transient outward
      (IA) and delayed rectifying (IK) K+ currents. We aim to clarify the subtype(s) of
      SSTRs involved in K+ current enhancement in GH3 somatotrope cells using specific
      SSTR subtype agonists. Expression of all five SSTRs was confirmed in GH3 cells by
      RT-PCR. Nystatin-perforated patch clamp was used to record voltage-gated K+
      currents. We first established the presence of IA and IK type K+ currents in GH3
      cells using different holding potentials (-40 or -70 mV) and specific blockers (4
      aminopirimidine and tetraethylammonium chloride). SRIF (200 nM) increased the
      amplitude of both IA and IK in a fully reversible manner. Various concentrations
      of each specific SRTR agonist were tested on K+ currents to find the maximal
      effective concentration. Activation of SSTR2 and SSTR4 by their respective
      agonists, L-779,976 and L-803,087 (10 nM), increased K+ current amplitude without
      preference to IA or IK, and abolished any further increase by SRIF. Activation of
      SSTR1 and SSTR5 by their respective agonists, L-797,591 or L-817,818 (10 nM),
      increased K+ current amplitude, but SRIF evoked a further increase. The SSTR3
      agonist L-797,778 (10 nM) did not affect the K+ currents or the response to SRIF.
      These results indicate that SSTR1, -2, -4, and -5 may all be involved in the
      enhancement of K+ currents by SRIF but that only the activation of SSTR2 or -4
      results in the full activation of K+ current caused by SRIF.

PMID- 16081635
TI  - Analysis of the biochemical mechanisms for the endocrine actions of fibroblast
      growth factor-23.
AB  - Fibroblast growth factor (FGF)-23 has emerged as an endocrine regulator of
      phosphate and of vitamin D metabolism. It is produced in bone and, unlike other
      FGFs, circulates in the bloodstream to ultimately regulate phosphate handling and
      vitamin D production in the kidney. Presently, it is unknown which of the seven
      principal FGF receptors (FGFRs) transmits FGF23 biological activity. Furthermore,
      the molecular basis for the endocrine mode of FGF23 action is unclear. Herein, we
      performed surface plasmon resonance and mitogenesis experiments to
      comprehensively characterize receptor binding specificity. Our data demonstrate
      that FGF23 binds and activates the c splice isoforms of FGFR1-3, as well as
      FGFR4, but not the b splice isoforms of FGFR1-3. Interestingly, highly sulfated
      and longer glycosaminoglycan (GAG) species were capable of promoting FGF23
      mitogenic activity. We also show that FGF23 induces tyrosine phosphorylation and
      inhibits sodium-phosphate cotransporter Npt2a mRNA expression using opossum
      kidney cells, a model kidney proximal tubule cell line. Removal of cell surface
      GAGs abolishes the effects of FGF23, and exogenous highly sulfated GAG is capable
      of restoring FGF23 activity, suggesting that proximal tubule cells naturally
      express GAGs that are permissive for FGF23 action. We propose that FGF23 signals
      through multiple FGFRs and that the unique endocrine actions of FGF23 involve
      escape from FGF23-producing cells and circulation to the kidney, where highly
      sulfated GAGs most likely act as cofactors for FGF23 activity. Our biochemical
      findings provide important insights into the molecular mechanisms by which
      dysregulated FGF23 signaling leads to disorders of hyper- and hypophosphatemia.

PMID- 16081636
TI  - Different configurations of specific thyroid hormone response elements mediate
      opposite effects of thyroid hormone and GC-1 on gene expression.
AB  - T3 regulates transcription of the rat sarcoendoplasmic reticulum calcium ATPase
      in the heart. The T3 effect is mediated by three differently configured T3
      response elements (TREs). Here we report the mutation of each individual TRE in
      the promoter and the contribution of each TRE on gene expression. Mutation of
      TRE1, a direct repeat element, exerted the strongest T3 response, compared with
      TRE2 and TRE3, which are inverted palindromes. The isolated TRE2 and TRE3, which
      showed no response (TRE2) or were weakly positive with T3 (TRE3), became strong
      negative regulatory elements with the T3 analog GC-1. We found that TRE1 recruits
      corepressor complexes containing nuclear receptor corepressor and histone
      deacetylase 3 in the absence of ligand, and steroid receptor coactivator-1
      containing coactivator complexes with both T3 and GC-1. TRE3 bound the same
      corepressor complexes without ligand but showed only a weak association with
      steroid receptor coactivator-1 with T3 and a strong association with corepressor
      complexes with GC-1. Thus, GC-1 appears to control cofactor association
      differentially on these two sarcoendoplasmic reticulum calcium ATPase TREs, which
      could be the mechanism of ligand-dependent transcriptional activation and
      repression observed with the isolated TRE1 and TRE3 elements. Because the x-ray
      crystal structures of GC-1 and T3 complexed with the TR ligand binding domain are
      superimposable, the results imply that GC-1 and T3 induce differential effects on
      the receptor that are not evident in the static structures but must occur in the
      dynamic setting of receptor function. These results have implications for
      selective modulation of receptor function by agonist ligands.

PMID- 16081637
TI  - Reduction in adiposity affects the extent of afferent projections to growth
      hormone-releasing hormone and somatostatin neurons and the degree of
      colocalization of neuropeptides in growth hormone-releasing hormone and
      somatostatin cells of the ovine hypothalamus.
AB  - Various neuropeptides and neurotransmitters affect GH secretion by acting on GHRH
      and somatostatin (SRIF) cells. GH secretion is also affected by alteration in
      adiposity, which could be via modulation of GHRH and SRIF cells. We quantified
      colocalization of neuropeptides in GHRH and SRIF cells and afferent projections
      to these cells in lean (food restricted) and normally fed sheep (n=4/group). The
      number of GHRH-immunoreactive (IR) cells in the arcuate nucleus was higher in
      lean animals, but the number of SRIF-IR cells in the periventricular nucleus was
      similar in the two groups. A subpopulation of GHRH-IR cells colocalized
      neuropeptide Y in lean animals, but this was not seen in normally fed animals.
      GHRH/galanin (GAL) colocalization was higher in lean animals with no difference
      in numbers of GHRH/tyrosine hydroxylase or GHRH/GAL-like peptide cells.
      SRIF/enkephalin colocalization was lower in lean animals. The percentage of GHRH
      neurons receiving SRIF input was similar in lean and normally fed animals, but
      more GHRH cells received input from enkephalin afferents in normally fed animals.
      The percentage of SRIF cells receiving GHRH, neuropeptide Y, GAL, and orexin
      afferents was higher in lean animals. These findings provide an anatomical
      evidence of central mechanism(s) by which appetite-regulating peptides and
      dopamine could regulate GH secretion. Increased input to SRIF cells in lean
      animals may be inhibitory and permissive of increased GH. The appearance of NPY
      in GHRH cells of lean animals may be a mechanism for regulation of increasing GH
      secretion with reduced adiposity.

PMID- 16081638
TI  - Expression of the GTP-binding protein (Galphas) is repressed by the nuclear
      factor kappaB RelA subunit in human myometrium.
AB  - In humans, the factors that govern the switch from myometrial quiescence to
      coordinated contractions at the initiation of labor are not well defined. The
      onset of parturition is itself associated with increases in a number of
      proinflammatory mediators, many of which are regulated by the nuclear factor
      kappaB (NF-kappaB) family of transcription factors. Recently, we have provided
      evidence that the RelA NF-kappaB subunit associates with protein kinase A in
      pregnant myometrial tissue, suggesting links with the Galphas/cAMP/protein kinase
      A pathway. TNFalpha is a potent activator of NF-kappaB, and levels of this
      cytokine are increased within the myometrium at term. In the current study, using
      primary cultures of myometrial cells, TNFalpha was observed to repress expression
      of Galphas while, at the same time, stimulating NF-kappaB activity. Furthermore,
      this effect could be replicated by exposure to bacterial lipopolysaccharide and
      exogenous expression of RelA. Moreover, TNFalpha was seen to repress endogenous
      Galphas mRNA expression as judged by RT-PCR analyses. Using the chromatin
      immunoprecipitation assay, we show that RelA did not bind directly to the Galphas
      promoter. Significantly, expression of a coactivator protein, cAMP response
      element binding protein binding protein, relieved RelA-induced down-regulation of
      Galphas expression. Together, these data suggest that, in human myometrium,
      repression of the Galphas gene by NF-kappaB occurs through a non-DNA binding
      mechanism involving competition for limiting amounts of cellular coactivator
      proteins including cAMP response element binding protein binding protein.

PMID- 16081639
TI  - Janus kinase 2 enhances the stability of the mature growth hormone receptor.
AB  - The abundance of surface GH receptor (GHR) is an important determinant of
      cellular GH sensitivity and is regulated at both transcriptional and
      posttranscriptional levels. In previous studies of GHR-expressing Janus kinase 2
      (JAK2)-deficient human fibrosarcoma cells (gamma2A-GHR), we demonstrated that
      stable transfection with JAK2 resulted in increased steady-state levels of mature
      GHR (endoH-resistant; relative molecular mass, 115-140 kDa) relative to precursor
      GHR (endoH-sensitive; relative molecular mass, 100 kDa). We now examine further
      the effects of JAK2 on GHR trafficking by comparing gamma2A-GHR to gamma2A-GHR
      cells stably reconstituted with JAK2 (C14 cells). In the presence of JAK2, GHR
      surface expression was increased, as assessed by surface biotinylation, 125I
      labeled human GH cell surface binding, and immunofluorescence microscopy assays.
      Although the absence of JAK2 precluded GH-stimulated signaling, GH-induced GHR
      disulfide linkage (a proxy for the GH-induced conformational changes in the GHR
      dimer) proceeded independent of JAK2 expression, indicating that the earliest
      steps in GH-induced GHR triggering are not prevented by the absence of JAK2. RNA
      interference-mediated knockdown of JAK2 in C14 cells resulted in a decreased
      mature to precursor ratio, supporting a primary role for JAK2 either in enhancing
      GHR biogenesis or dampening mature GHR degradation. To address these potential
      mechanisms, metabolic pulse-chase labeling experiments and experiments in which
      the fate of previously synthesized GHR was followed by anti-GHR immunoblotting
      after cycloheximide treatment (cycloheximide chase experiments) were performed.
      These indicated that the presence of JAK2 conferred modest enhancement (1.3- to
      1.5-fold) in GHR maturation but substantially prolonged the t1/2 of the mature
      GHR, suggesting a predominant effect on mature GHR stability. Cycloheximide chase
      experiments with metalloprotease, proteasome, and lysosome inhibitors indicated
      that the enhanced stability of mature GHR conferred by JAK2 is not related to
      effects on constitutive receptor metalloproteolysis but rather is a result of
      reduced constitutive endosomal/lysosomal degradation of the mature GHR. These
      results are discussed in the context of emerging information on how JAK-family
      members modulate surface expression of other cytokine receptors.

PMID- 16081640
TI  - Transgenic angiopoietin-like (angptl)4 overexpression and targeted disruption of
      angptl4 and angptl3: regulation of triglyceride metabolism.
AB  - Lipoprotein lipase (LPL) is a key regulator of triglyceride clearance. Its
      coordinated regulation during feeding and fasting is critical for maintaining
      lipid homeostasis and energy supply. Angiopoietin-like (Angptl)3 and Angptl4 are
      secreted proteins that have been demonstrated to regulate triglyceride metabolism
      by inhibiting LPL. We have taken a targeted genetic approach to generate Angptl4-
      and Angptl3-deficient mice as well as transgenic mice overexpressing human
      Angptl4 in the liver. The Angptl4 transgenic mice displayed elevated plasma
      triglycerides and reduced postheparin plasma (PHP) LPL activity. A purified
      recombinant Angptl4 protein inhibited mouse LPL and recombinant human LPL
      activity in vitro. In contrast to the transgenic mice, Angptl4-deficient mice
      displayed hypotriglyceridemia and increased PHP LPL activity, with greater
      effects in the fasted compared with the fed state. Angptl3-deficient mice also
      displayed hypotriglyceridemia with elevated PHP LPL activity, but these mice
      showed a greater effect in the fed state. Mice deficient in both Angptl proteins
      showed an additive effect on plasma triglycerides and did not survive past 2
      months of age. Our results show that Angptl3 and Angptl4 function to regulate
      circulating triglyceride levels during different nutritional states and therefore
      play a role in lipid metabolism during feeding/fasting through differential
      inhibition of LPL.

PMID- 16081641
TI  - Transforming growth factor beta-activated kinase 1 is a key mediator of ovine
      follicle-stimulating hormone beta-subunit expression.
AB  - FSH, a key regulator of gonadal function, contains a beta-subunit (FSHbeta) that
      is transcriptionally induced by activin, a member of the TGFbeta-superfamily.
      This study used 4.7 kb of the ovine FSHbeta-promoter linked to luciferase
      (oFSHbetaLuc) plus a well-characterized activin-responsive construct, p3TPLuc, to
      investigate the hypothesis that Smad3, TGFbeta-activated kinase 1 (TAK1), or both
      cause activin-mediated induction of FSH. Overexpression of either Smad3 or TAK1
      induced oFSHbetaLuc in gonadotrope-derived LbetaT2 cells as much as activin
      itself. Induction of p3TPLuc by activin is known to require Smad3 activation in
      many cell types, and this was true in LbetaT2 cells, where 10-fold induction by
      activin (2-8 h after activin treatment) was blocked more than 90% by two dominant
      negative (DN) inhibitors of Smad3 [DN-Smad3 (3SA) and DN-Smad3 (D407E)]. By
      contrast, 6.5-fold induction of oFSHbetaLuc by activin (10-24 h after activin
      treatment) was not blocked by either DN-Smad inhibitor, suggesting that
      activation of Smad3 did not trigger induction of oFSHbetaLuc. By contrast,
      inhibition of TAK1 by a DN-TAK1 construct led to a 50% decrease in activin
      mediated induction of oFSHbetaLuc, and a specific inhibitor of TAK1 (5Z-7
      Oxozeanol) blocked induction by 100%, indicating that TAK1 is necessary for
      activin induction of oFSHbetaLuc. Finally, inhibiting p38-MAPK (often activated
      by TAK1) blocked induction of oFSHbetaLuc by 60%. In conclusion, the data
      presented here indicate that activation of TAK1 (and probably p38-MAPK), but not
      Smad3, is necessary for triggering induction of oFSHbeta by activin.

PMID- 16081642
TI  - Urocortin 2 suppresses host resistance to Listeria monocytogenes infection via up
      regulation of interleukin-10.
AB  - Previous studies have showed that corticotropin-releasing factor (CRF) modulates
      immune response during inflammation. We investigated the effect of CRF family
      peptides on host resistance to Listeria monocytogenes infection in mice. When
      mice were administered ip with CRF, urocortin (Ucn), or Ucn2 30 min prior a
      sublethal infection with L. monocytogenes, the numbers of bacteria in the organs
      of Ucn2-treated mice were dramatically increased, and most of these mice
      succumbed. However, host resistance to the infection was retained in CRF- or Ucn
      treated mice. The suppressive effect of Ucn2 was dependent on CRF receptor type 2
      because an antagonist to the receptor canceled the effect of Ucn2. IL-10
      production was significantly increased, and interferon-gamma and TNFalpha
      production was decreased in the spleens of Ucn2-treated mice, compared with those
      in Ucn2-untreated control mice. The effect of Ucn2 was canceled by treatment with
      anti-IL-10 monoclonal antibody and in IL-10-deficient mice. The expression and
      activation of signal transducers and activators of transcription (STAT) 3 were up
      regulated, and the expression and activation of STAT1 were down-regulated in the
      spleens from Ucn2-treated mice, compared with vehicle-treated mice. Moreover,
      suppression of TNFalpha production and augmentation of IL-10 production and
      expression and activation of STAT3 by Ucn2 treatment were observed in heat-killed
      L. monocytogenes-stimulated macrophages. These results suggested that Ucn2
      suppresses host resistance to L. monocytogenes infection via up-regulation of IL
      10 production.

PMID- 16081643
TI  - Growth hormone-releasing peptide hexarelin reduces neonatal brain injury and
      alters Akt/glycogen synthase kinase-3beta phosphorylation.
AB  - Hexarelin (HEX) is a peptide GH secretagogue with a potent ability to stimulate
      GH secretion and recently reported cardioprotective actions. However, its effects
      in the brain are largely unknown, and the aim of the present study was to examine
      the potential protective effect of HEX on the central nervous system after
      injury, as well as on caspase-3, Akt, and extracellular signal-regulated protein
      kinase (ERK) signaling cascades in a rat model of neonatal hypoxia-ischemia.
      Hypoxic-ischemic insult was induced by unilateral carotid ligation and hypoxic
      exposure (7.7% oxygen), and HEX treatment was administered
      intracerebroventricularly, directly after the insult. Brain damage was quantified
      at four coronal levels and by regional neuropathological scoring. Brain damage
      was reduced by 39% in the treatment group, compared with vehicle group, and
      injury was significantly reduced in the cerebral cortex, hippocampus, and
      thalamus but not in the striatum. The cerebroprotective effect was accompanied by
      a significant reduction of caspase-3 activity and an increased phosphorylation of
      Akt and glycogen synthase kinase-3beta, whereas ERK was unaffected. In
      conclusion, we demonstrate for the first time that HEX is neuroprotective in the
      neonatal setting in vivo and that increased Akt signaling is associated with
      downstream attenuation of glycogen synthase kinase-3beta activity and caspase
      dependent cell death.

PMID- 16081644
TI  - Dominant role of mitochondria in calcium homeostasis of single rat pituitary
      corticotropes.
AB  - The rise in cytosolic free Ca2+ concentration ([Ca2+]i) is the major trigger for
      secretion of ACTH from pituitary corticotropes. To better understand the shaping
      of the Ca2+ signal in corticotropes, we investigated the mechanisms regulating
      the depolarization-triggered Ca2+ signal using patch-clamp techniques and indo-1
      fluorometry. The rate of cytosolic Ca2+ clearance was unaffected by inhibitors of
      Na+/Ca2+ exchanger or plasma membrane Ca2+-ATPase (PMCA), slightly slowed by
      sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor, but dramatically
      slowed by mitochondrial uncouplers or inhibitor of mitochondrial uniporter.
      Measurements with rhod-2 revealed that depolarization-triggered increase in
      mitochondrial Ca2+ concentration. Thus, mitochondria have a dominant role in
      cytosolic Ca2+ clearance. Using the Mn2+ quench technique, we found the presence
      of a continuous basal Ca2+ influx in corticotropes. This basal Ca2+ influx was
      balanced by the combined actions of mitochondrial uniporter and PMCA and SERCA
      pumps. Inhibition of the mitochondrial uniporter or PMCA or SERCA pumps elevated
      basal [Ca2+]i. Using membrane capacitance measurement, we found that the change
      in the shape of the depolarization-triggered Ca2+ signal after mitochondrial
      inhibition was associated with enhancement of the exocytotic response. Thus,
      mitochondria have a dominant role in the regulation of Ca2+ signal and exocytosis
      in corticotropes.

PMID- 16081645
TI  - Cells of the osteoclast lineage as mediators of the anabolic actions of
      parathyroid hormone in bone.
AB  - PTH is an anabolic agent used to treat osteoporosis, but its mechanisms of action
      are unclear. This study elucidated target cells and mechanisms for anabolic
      actions of PTH in mice during bone growth. Mice with c-fos ablation are
      osteopetrotic and lack an anabolic response to PTH. In this study, there were no
      alterations in PTH-regulated osteoblast differentiation or proliferation in vitro
      in cells from c-fos -/- mice compared with +/+; hence, the impact of osteoclastic
      cells was further investigated. A novel transplant model was used to rescue the
      osteopetrotic defect of c-fos ablation. Vertebral bodies (vossicles) from c-fos 
      /- and +/+ mice were implanted into athymic hosts, and the c-fos -/- osteoclast
      defect was rescued. PTH treatment to vossicle-bearing mice increased 5-bromo-2'
      deoxyuridine (BrdU) positivity in the bone marrow and increased bone area
      regardless of the vossicle genotype. To inhibit recruitment of osteoclast
      precursors to wild-type vossicles, stromal derived factor-1 signaling was
      blocked, which blunted the PTH anabolic response. Treating mice with
      osteoprotegerin to inhibit osteoclast differentiation also blocked the anabolic
      action of PTH. In contrast, using c-src mutant mice with a late osteoclast
      differentiation defect did not hinder the anabolic action, suggesting key target
      cells reside in the intermediately differentiated osteoclast population in the
      bone marrow. These results indicate that c-fos in osteoblasts is not critical for
      PTH action but that cells of the osteoclast lineage are intermediate targets for
      the anabolic action of PTH.

PMID- 16081646
TI  - Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin
      by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis.
AB  - Both chronic excess of PTH, as in hyperparathyroidism, and intermittent elevation
      of PTH (by daily injections) increase the number of osteoblasts; albeit, the
      former is associated with bone catabolism and the later with bone anabolism.
      Intermittent PTH increases osteoblast number by attenuating osteoblast apoptosis,
      an effect that requires the transcription factor Runx2. However, chronic
      elevation of PTH does not affect osteoblast apoptosis because it stimulates the
      proteasomal degradation of Runx2. Here, we studied the effects of PTH on Sost, a
      Runx2 target gene expressed in osteocytes (former osteoblasts embedded in the
      bone matrix), which antagonizes the pro-osteoblastogenic actions of bone
      morphogenetic proteins and Wnts. We report that continuous infusion of PTH to
      mice for 4 d decreased Sost mRNA expression in vertebral bone by 80-90%. This
      effect was accompanied by a comparable reduction of sclerostin, the product of
      Sost, in osteocytes, as determined by quantitative immunoblot analysis of bone
      extracts and by immunostaining. In contrast, a single injection of PTH caused a
      transient 50% reduction in Sost mRNA at 2 h, but four daily injections had no
      effect on Sost mRNA or sclerostin. PTH strongly decreased Sost expression in
      osteocytes formed in primary cultures of neonatal murine calvaria cells as well
      as in osteocytic MLO-A5 cells, demonstrating a direct effect of PTH on this cell
      type. These results, together with evidence that sclerostin antagonizes bone
      morphogenetic proteins and Wnts, strongly suggest that suppression of Sost by PTH
      represents a novel mechanism for hormonal control of osteoblastogenesis mediated
      by osteocytes.

PMID- 16081647
TI  - Characterization and enzymatic degradation of Sup35NM, a yeast prion-like
      protein.
AB  - Transmissible spongiform encephalopathies (TSEs) are believed to be caused by an
      unconventional infectious agent, the prion protein. The pathogenic and infectious
      form of prion protein, PrPSc, is able to aggregate and form amyloid fibrils, very
      stable and resistant to most disinfecting processes and common proteases. Under
      specific conditions, PrPSc in bovine spongiform encephalopathy (BSE) brain tissue
      was found degradable by a bacterial keratinase and some other proteases. Since
      this disease-causing prion is infectious and dangerous to work with, a model or
      surrogate protein that is safe is needed for the in vitro degradation study. Here
      a nonpathogenic yeast prion-like protein, Sup35NM, cloned and overexpressed in E.
      coli, was purified and characterized for this purpose. Aggregation and
      deaggregation of Sup35NM were examined by electron microscopy, gel
      electrophoresis, Congo red binding, fluorescence, and Western blotting. The
      degradation of Sup35NM aggregates by keratinase and proteinase K under various
      conditions was studied and compared. These results will be of value in
      understanding the mechanism and optimization of the degradation process.

PMID- 16081648
TI  - Three amino acids that are critical to formation and stability of the P22
      tailspike trimer.
AB  - The P22 tailspike protein folds by forming a folding competent monomer species
      that forms a dimeric, then a non-native trimeric (protrimer) species by addition
      of folding competent monomers. We have found three residues, R549, R563, and
      D572, which play a critical role in both the stability of the native tailspike
      protein and assembly and maturation of the protrimer. King and colleagues
      reported previously that substitution of R563 to glutamine inhibited protrimer
      formation. We now show that the R549Q and R563K variants significantly delay the
      protrimer-to-trimer transition both in vivo and in vitro. Previously, variants
      that destabilize intermediates have shown wild-type chemical stability.
      Interestingly, both the R549Q and R563K variants destabilize the tailspike trimer
      in guanidine denaturation studies, indicating that they represent a new class of
      tailspike folding variants. R549Q has a midpoint of unfolding at 3.2M guanidine,
      compared to 5.6M for the wild-type tailspike protein, while R563K has a midpoint
      of unfolding of 1.8 M. R549Q and R563K also denature over a broader pH range than
      the wild-type tailspike protein and both proteins have increased sensitivity to
      pH during refolding, suggesting that both residues are involved in ionic
      interactions. Our model is that R563 and D572 interact to stabilize the adjacent
      turn, aiding the assembly of the dimer and protrimer species. We believe that the
      interaction between R563 and D572 is also critical following assembly of the
      protrimer to properly orient D572 in order to form a salt bridge with R549 during
      protrimer maturation.

PMID- 16081649
TI  - Thioredoxin-like domain of human kappa class glutathione transferase reveals
      sequence homology and structure similarity to the theta class enzyme.
AB  - Glutathione transferases (GSTs) are a superfamily of enzymes that play a vital
      functional role in the cellular detoxification process. They catalyze the
      conjugation of the thiol group of glutathione (GSH) to the electrophilic groups
      of a wide range of hydrophobic substrates, leading to an easier removal of the
      latter from the cells. The kappa class is the least studied one among various
      classes within the superfamily. We report here the expression, purification, and
      crystal structure of human kappa class GST (hGSTK), which has been determined by
      the multiple-isomorphous replacement method and refined to 1.93 A resolution. The
      overall structure of hGSTK is similar to the recently reported structure of kappa
      class GST from rat mitochondrion. Each subunit of the dimeric hGSTK contains a
      thioredoxin (TRX)-like domain and a helical domain. A molecule of glutathione
      sulfinate, an oxidized product of GSH, is found to bind at the G site of each
      monomer. One oxygen atom of the sulfino group of GSF forms a hydrogen bond with
      the hydroxyl group of the catalytic residue Ser16. The TRX-like domain of hGSTK
      shares 19% sequence identity and structure similarity with human theta class GST,
      suggesting that the kappa class of GST is more closely related to the theta class
      enzyme within the GST superfamily. The structure of the TRX-like domain of hGSTK
      is also similar to that of glutathione peroxidase (GPx), implying an evolutionary
      relationship between GST and GPx.

PMID- 16081650
TI  - Ionic interactions at both inter-ring contact sites of GroEL are involved in
      transmission of the allosteric signal: a time-resolved infrared difference study.
AB  - The biological activity of the double-ring chaperonin GroEL is regulated by
      complex allosteric interactions, which include positive intra-ring and negative
      inter-ring cooperativity. To further characterize inter-ring communication, the
      nucleotide-induced absorbance changes in the vibrational spectrum of the
      chaperonin GroEL, of two single-point mutants suppressing one inter-ring ionic
      contact (E461K and E434K) and of a single-ring version of this protein, were
      investigated by time-resolved infrared difference spectroscopy. Interaction of
      the nucleotide with the proteins was triggered by its photochemical release from
      a biologically inactive caged precursor [P3-1-(2-nitro) phenylethyl nucleotide].
      The results indicate that (1) ATP binding to the protein induces a conformational
      change that affects concomitantly both intra-ring and inter-ring communication,
      and (2) the experimental absorbance changes are sensitive to the double-ring
      structure of the protein. The characterization of the single-point, inter-ring
      mutants demonstrates that ionic interactions at both contact sites are involved
      in the transmission of the allosteric signal. However, both mutations have
      different effects on the inter-ring interface. While that of E461K still retains
      ionic contacts sensitive to ATP binding, E434K shows spectroscopic features
      similar to those of the single-ring version of the protein, therefore suggesting
      that electrostatic interactions at these contact sites contribute differently to
      the stability of the inter-ring interface.

PMID- 16081651
TI  - Structural characterization of the maytansinoid-monoclonal antibody
      immunoconjugate, huN901-DM1, by mass spectrometry.
AB  - Immunoconjugates are being explored as novel cancer therapies with the promise of
      target-specific drug delivery. The immunoconjugate, huN901-DM1, composed of the
      humanized monoclonal IgG1 antibody, huN901, and the maytansinoid drug, DM1, is
      being tested in clinical trials to treat small cell lung carcinoma (SCLC). huN901
      DM1 contains an average of three to four DM1 drug molecules per huN901 antibody
      molecule. The drug molecules are linked to huN901 through random modification of
      huN901 at epsilon-amino groups of lysine residues, thus yielding a heterogeneous
      population of conjugate species. We studied the drug distribution profile of
      huN901-DM1 by electrospray time-of-flight mass spectrometry(ESI-TOFMS), which
      showed that one to six DM1 drug molecules were attached to an antibody molecule.
      Both light and heavy chains contained linked drugs. The conjugation sites in both
      chains were determined by peptide mapping using trypsin and Asp-N protease
      digestion. Trypsin digestion identified modified lysine residues, since these
      residues were no longer susceptible to enzymatic cleavage after conjugation with
      the drug. With respect to Asp-N digestion, modified peptides were identified by
      observing a mass increase corresponding to the modification. The two digestion
      methods provided consistent results, leading to the identification of 20 modified
      lysine residues in both light and heavy chains. Each lysine residue was only
      partially modified. No conjugation sites were found in complementarity
      determining regions (CDRs). Using structural models of human IgG1, it was found
      that modified lysine residues were on the surface in areas of structural
      flexibility and had large solvent accessibility.

PMID- 16081652
TI  - Nuclear transfer of perchloric acid-soluble protein by endoplasmic reticulum
      stressors.
AB  - Perchloric acid-soluble protein (PSP) is highly conserved during evolution from
      bacteria to mammals. Although PSP has been recognized as an inhibitor of
      translation and proliferation in vitro, its precise biological role has not yet
      been elucidated. Since we previously found similar distributions for PSP and the
      endoplasmic reticulum (ER) and Golgi complex, the intracellular distribution of
      PSP was analyzed in more detail. Immunofluorescence studies indicated that PSP co
      localized with the ER and Golgi complex, since the distribution pattern of PSP
      was well matched to both of these organelles. An immunoelectron microscopic study
      revealed PSP was located not only in the cytosol but also on the surface of the
      outer ER membrane. Since PSP was present on the ER, we speculated that it may be
      associated with ER function. Therefore, we analyzed whether or not the ER stress
      response, which is one of the ER functions, affected PSP expression. The results
      showed that various ER stressors (thapsigargin, A23187, tunicamycin, brefeldin A,
      and cisplatin) provoked a dramatic change in the localization of PSP from outside
      of the nucleus to inside the nucleus within 3 h. Moreover, the ER stressors
      induced PSP expression. These results suggest that PSP is involved in the
      cellular response to ER stressors, and that the change in localization of PSP
      from the ER to the nucleus may be associated with ER stress responses.

PMID- 16081653
TI  - High-pressure studies of aggregation of recombinant human interleukin-1 receptor
      antagonist: thermodynamics, kinetics, and application to accelerated formulation
      studies.
AB  - Recombinant human interleukin-1 receptor antagonist (IL-1ra) in aqueous solutions
      unfolds and aggregates when subjected to hydrostatic pressures greater than about
      180 MPa. This study examined the mechanism and thermodynamics of pressure-induced
      unfolding and aggregation of IL-1ra. The activation free energy for growth of
      aggregates (DeltaG-/+(aggregation)) was found to be 37 +/- 3 kJ/mol, whereas the
      activation volume (DeltaV-/+(aggregation)) was -120 +/- 20 mL/mol. These values
      compare closely with equilibrium values for denaturation: The free energy for
      denaturation, DeltaG(denaturation), was 20 +/- 5 kJ/mol, whereas the partial
      specific volume change for denaturation, DeltaV(denaturation), was -110 +/- 30
      mL/mol. When IL-1ra begins to denature at pressures near 140 MPa, cysteines that
      are normally buried in the native state become exposed. Under oxidizing
      conditions, this results in the formation of covalently cross-linked aggregates
      containing nonnative, intermolecular disulfide bonds. The apparent activation
      free energy for nucleation of aggregates, DeltaG-/+(nuc), was 42 +/- 4 kJ/mol,
      and the activation volume for nucleation, DeltaV-/+(nuc),was -175 +/- 37 mL/mol,
      suggesting that a highly solvent-exposed conformation is needed for nucleation.
      We hypothesize that the large specific volume of IL-1ra, 0.752 +/- 0.004 mL/g,
      coupled with its relatively low conformational stability, leads to its
      susceptibility to denaturation at relatively low pressures. The positive partial
      specific adiabatic compressibility of IL-1ra, 4.5 +/- 0.7 +/- 10(-12) cm2/dyn,
      suggests that a significant component of the DeltaV(denaturation) is attributable
      to the elimination of solvent-free cavities. Lastly, we propose that hydrostatic
      pressure is a useful variable to conduct accelerated formulation studies of
      therapeutic proteins.

PMID- 16081654
TI  - Redesigning symmetry-related "mini-core" regions of FGF-1 to increase primary
      structure symmetry: thermodynamic and functional consequences of structural
      symmetry.
AB  - Previous reports detailing mutational effects within the hydrophobic core of
      human acidic fibroblast growth factor (FGF-1) have shown that a symmetric primary
      structure constraint is compatible with a stably folded protein. In the present
      report, we investigate symmetrically related pairs of buried hydrophobic residues
      in FGF-1 (termed "mini-cores") that are not part of the central core. The effect
      upon the stability and function of FGF-1 mutations designed to increase primary
      structure symmetry within these "mini-core" regions was evaluated. At symmetry
      related positions 22, 64, and 108, the wild-type protein contains either Tyr or
      Phe side chains. The results show that either residue can be readily accommodated
      at these positions. At symmetry-related positions 42, 83, and 130, the wild-type
      protein contains either Cys or Ile side chains. While positions 42 and 130 can
      readily accommodate either Cys or Ile side chains, position 83 is substantially
      destabilized by substitution by Ile. Tertiary structure asymmetry in the vicinity
      of position 83 appears responsible for the inability to accommodate an Ile side
      chain at this position, and is known to contribute to functional half-life. A
      mutant form of FGF-1 with enforced primary structure symmetry at positions 22,
      64, and 108 (all Tyr) and 42, 83, and 130 (all Cys) is shown to be more stable
      than the reference FGF-1 protein. The results support the hypothesis that a
      symmetric primary structure within a symmetric protein superfold represents a
      solution to achieving a foldable, stable polypeptide, and highlight the role that
      function may play in the evolution of asymmetry within symmetric superfolds.

PMID- 16081655
TI  - Solution structure of the C1-subdomain of Bacillus stearothermophilus translation
      initiation factor IF2.
AB  - IF2 is one of three bacterial translation initiation factors that are conserved
      through all kingdoms of life. It binds the 30S and 50S ribosomal subunits, as
      well as fMet-tRNAf(Met). After these interactions, fMet-tRNAf(Met) is oriented to
      the ribosomal P-site where the first amino acid of the nascent polypeptide,
      formylmethionine, is presented. The C-terminal domain of Bacillus
      stearothermophilus IF2, which is responsible for recognition and binding of fMet
      tRNAf(Met), contains two structured modules. Previously, the solution structure
      of the most C-terminal module, IF2-C2, has been elucidated by NMR spectroscopy
      and direct interactions between this subdomain and fMet-tRNAf(Met) were reported.
      In the present NMR study we have obtained the spectral assignment of the other
      module of the C-terminal domain (IF2-C1) and determined its solution structure
      and backbone dynamics. The IF2-C1 core forms a flattened fold consisting of a
      central four-stranded parallel beta-sheet flanked by three alpha-helices.
      Although its overall organization resembles that of subdomain III of the archaeal
      IF2-homolog eIF5B whose crystal structure had previously been reported, some
      differences of potential functional significance are evident.

PMID- 16081656
TI  - Frog albumin is expressed in skin and characterized as a novel potent trypsin
      inhibitor.
AB  - A novel potent trypsin inhibitor was purified and characterized from frog Bombina
      maxima skin. A full-length cDNA encoding the protein was obtained from a cDNA
      library constructed from the skin. Sequence analysis established that the protein
      actually comprises three conserved albumin domains. B.maxima serum albumin was
      subsequently purified, and its coding cDNA was further obtained by PCR-based
      cloning from the frog liver. Only two amino acid variations were found in the
      albumin sequences from the skin and the serum. However, the skin protein is
      distinct from the serum protein by binding of a haem b (0.95 mol/mol protein).
      Different from bovine serum albumin, B. maxima albumin potently inhibited
      trypsin. It bound tightly with trypsin in a 1:1 molar ratio. The equilibrium
      dissociation constants (KD) obtained for the skin and the serum proteins were
      1.92 x 10(-9) M and 1.55 x 10(-9) M, respectively. B. maxima albumin formed a
      noncovalent complex with trypsin through an exposed loop formed by a disulfide
      bond (Cys53-Cys62), which comprises the scissile bond Arg58(P1)-His59(P1'). No
      inhibitory effects on thrombin, chymotrypsin, elastase, and subtilisin were
      observed under the assay conditions. Immunohistochemical study showed that B.
      maxima albumin is widely distributed around the membranes of epithelial layer
      cells and within the stratum spongiosum of dermis in the skin, suggesting that it
      plays important roles in skin physiological functions, such as water economy,
      metabolite exchange, and osmoregulation.

PMID- 16081657
TI  - Localization of protein-binding sites within families of proteins.
AB  - We address the question of whether or not the positions of protein-binding sites
      on homologous protein structures are conserved irrespective of the identities of
      their binding partners. First, for each domain family in the Structural
      Classification of Proteins (SCOP), protein-binding sites are extracted from our
      comprehensive database of structurally defined binary domain interactions
      (PIBASE). Second, the binding sites within each family are superposed using a
      structural alignment of its members. Finally, the degree of localization of
      binding sites within each family is quantified by comparing it with localization
      expected by chance. We found that 72% of the 1847 SCOP domain families in PIBASE
      have binding sites with localization values greater than expected by chance.
      Moreover, 554 (30%) of these families have localizations that are statistically
      significant (i.e., more than four standard deviations away from the mean expected
      by chance). In contrast, only 144 (8%) families have significantly low
      localization. The absence of a significant correlation of the binding site
      localization with the average sequence and structural conservations in a family
      suggests that localization can be helpful for describing the functional diversity
      of protein-protein interactions, complementing measures of sequence and
      structural conservation. Consideration of the binding site localization may also
      result in spatial restraints for the modeling of protein assembly structures.

PMID- 16081658
TI  - Structure of the B3 domain from Arabidopsis thaliana protein At1g16640.
AB  - A novel DNA binding motif, the B3 domain, has been identified in a number of
      transcription factors specific to higher plant species, and was recently found to
      define a new protein fold. Here we report the second structure of a B3 domain,
      that of the Arabidopsis thaliana protein, At1g16640. As part of an effort to
      'rescue' structural genomics targets deemed unsuitable for structure
      determination as full-length proteins, we applied a combined bioinformatic and
      experimental strategy to identify an optimal construct containing a predicted
      conserved domain. By screening a series of N- and C-terminally truncated
      At1g16640 fragments, we isolated a stable folded domain that met our criteria for
      structural analysis by NMR spectroscopy. The structure of the B3 domain of
      At1g16640 consists of a seven-stranded beta-sheet arranged in an open barrel and
      two short alpha-helices, one at each end of the barrel. While At1g16640 is quite
      distinct from previously characterized B3 domain proteins in terms of amino acid
      sequence similarity, it adopts the same novel fold that was recently revealed by
      the RAV1 B3 domain structure. However, putative DNA-binding elements conserved in
      B3 domains from the RAV, ARF, and ABI3/VP1 subfamilies are largely absent in
      At1g16640, perhaps suggesting that B3 domains could function in contexts other
      than transcriptional regulation.

PMID- 16081659
TI  - Primary differentiation in the human blastocyst: comparative molecular portraits
      of inner cell mass and trophectoderm cells.
AB  - The primary differentiation event during mammalian development occurs at the
      blastocyst stage and leads to the delineation of the inner cell mass (ICM) and
      the trophectoderm (TE). We provide the first global mRNA expression data from
      immunosurgically dissected ICM cells, TE cells, and intact human blastocysts.
      Using a cDNA microarray composed of 15,529 cDNAs from known and novel genes, we
      identify marker transcripts specific to the ICM (e.g., OCT4/POU5F1, NANOG, HMGB1,
      and DPPA5) and TE (e.g., CDX2, ATP1B3, SFN, and IPL), in addition to novel ICM-
      and TE-specific expressed sequence tags. The expression patterns suggest that the
      emergence of pluripotent ICM and TE cell lineages from the morula is controlled
      by metabolic and signaling pathways, which include inter alia, WNT, mitogen
      activated protein kinase, transforming growth factor-beta, NOTCH, integrin
      mediated cell adhesion, phosphatidylinositol 3-kinase, and apoptosis. These data
      enhance our understanding of the first step in human cellular differentiation
      and, hence, the derivation of both embryonic stem cells and trophoblastic stem
      cells from these lineages.

PMID- 16081660
TI  - Shear-controlled single-step mouse embryonic stem cell expansion and embryoid
      body-based differentiation.
AB  - To facilitate the exploitation of embryonic stem cells (ESCs) and ESC-derived
      cells, scale-up of cell production and optimization of culture conditions are
      necessary. Conventional ESC culture methods are impractical for large-scale cell
      production and lack robust microenvironmental control. We developed two stirred
      suspension culture systems for the propagation of undifferentiated ESCs-
      microcarrier and aggregate cultures--and compared them with tissue-culture flask
      and Petri dish controls. ESCs cultured on glass microcarriers had population
      doubling times (approximately 14-17 hours) comparable to tissue-culture flask
      controls. ESC growth could be elicited in shear-controlled stirred-suspension
      culture, with population doubling times ranging between 24 and 39 hours at 100
      rpm impeller speed. Upon removal of leukemia inhibitory factor, the size
      controlled ESC aggregates developed into embryoid bodies (EBs) capable of
      multilineage differentiation. A comprehensive analysis of ESC developmental
      potential, including flow cytometry for Oct-4, SSEA-1, and E-cadherinprotein
      expression, reverse transcription-polymerase chain reaction for Flk-1, HNF3-beta,
      MHC, and Sox-1 gene expression, and EB differentiation analysis, demonstrated
      that the suspension-cultured ESCs retained the developmental potential of the
      starting cell population. Analysis of E-cadherin-/- and E-cadherin+/- cells using
      both systems provided insight into the mechanisms behind the role of cell
      aggregation control, which is fundamental to these observations. These cell
      culture tools should prove useful for both the production of ESCs and ESC-derived
      cells and for investigations into adhesion, survival, and differentiation
      phenomena during ESC propagation and differentiation.

PMID- 16081661
TI  - In vitro expansion of human mesenchymal stem cells: choice of serum is a
      determinant of cell proliferation, differentiation, gene expression, and
      transcriptome stability.
AB  - Human bone marrow mesenchymal stem cells (hMSCs) represent an appealing source of
      adult stem cells for cell therapy and tissue engineering, as they are easily
      obtained and expanded while maintaining their multilineage differentiation
      potential. All current protocols for in vitro culture of hMSCs include fetal
      bovine serum (FBS) as nutritional supplement. FBS is an undesirable additive to
      cells that are expanded for therapeutic purposes in humans because the use of FBS
      carries the risk of transmitting viral and prion diseases and proteins that may
      initiate xenogeneic immune responses. In the present study, we have therefore
      investigated if autologous serum (AS) or allogeneic human serum (alloHS) could
      replace FBS for the expansion of hMSCs in vitro. We discovered that the choice of
      serum affected hMSCs at several different levels. First, hMSCs in AS proliferated
      markedly faster than hMSCs in FBS, whereas use of alloHS resulted in hMSC growth
      arrest and death. Second, hMSCs in FBS differentiated more rapidly toward
      mesenchymal lineages compared with hMSCs in AS. Interestingly, genome-wide
      microarray analysis identified several transcripts involved in cell cycle and
      differentiation that were differentially regulated between hMSCs in FBS and AS.
      Finally, several transcripts, including some involved in cell cycle inhibition,
      were upregulated in hMSCs in FBS at a late passage, whereas the hMSC
      transcriptome in AS was remarkably stable. Thus, hMSCs may be expanded rapidly
      and with stable gene expression in AS in the absence of growth factors, whereas
      FBS induces a more differentiated and less stable transcriptional profile.

PMID- 16081662
TI  - Stem cell characteristics of amniotic epithelial cells.
AB  - Amniotic epithelial cells develop from the epiblast by 8 days after fertilization
      and before gastrulation, opening the possibility that they might maintain the
      plasticity of pregastrulation embryo cells. Here we show that amniotic epithelial
      cells isolated from human term placenta express surface markers normally present
      on embryonic stem and germ cells. In addition, amniotic epithelial cells express
      the pluripotent stem cell-specific transcription factors octamer-binding protein
      4 (Oct-4) and nanog. Under certain culture conditions, amniotic epithelial cells
      form spheroid structures that retain stem cell characteristics. Amniotic
      epithelial cells do not require other cell-derived feeder layers to maintain Oct
      4 expression, do not express telomerase, and are nontumorigenic upon
      transplantation. Based on immunohistochemical and genetic analysis, amniotic
      epithelial cells have the potential to differentiate to all three germ layers-
      endoderm (liver, pancreas), mesoderm (cardiomyocyte), and ectoderm (neural cells)
      in vitro. Amnion derived from term placenta after live birth may be a useful and
      noncontroversial source of stem cells for cell transplantation and regenerative
      medicine.

PMID- 16081663
TI  - Monitoring differentiation of human embryonic stem cells using real-time PCR.
AB  - There is a general lack of rapid, sensitive, and quantitative methods for the
      detection of differentiating human embryonic stem cells (hESCs). Using light
      microscopy and immunohistochemistry, we observed that morphological changes of
      differentiating hESCs precede any major alterations in the expression of several
      commonly used hESC markers (SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, Oct-4, and
      Nanog). In an attempt to quantify the changes during stochastic differentiation
      of hESCs, we developed a robust and sensitive multi-marker quantitative real-time
      polymerase chain reaction (QPCR) method. To maximize the sensitivity of the
      method, we measured the expression of up- and downregulated genes before and
      after differentiation of the hESCs. Out of the 12 genes assayed, we found it
      clearly sufficient to determine the relative differentiation state of the cells
      by calculating a collective expression index based on the mRNA levels of Oct-4,
      Nanog, Cripto, and alpha-fetoprotein. We evaluated the method using different
      hESC lines maintained in either feeder-dependent or feeder-free culture
      conditions. The QPCR method is very flexible, and by appropriately selecting
      reporter genes, the method can be designed for various applications. The
      combination of QPCR with hESC-based technologies opens novel avenues for high
      throughput analysis of hESCs in, for example, pharmacological and cytotoxicity
      screening.

PMID- 16081664
TI  - Human ERas gene has an upstream premature polyadenylation signal that results in
      a truncated, noncoding transcript.
AB  - The ERas gene is expressed in mouse embryonic stem (ES) cells and promotes their
      in vitro proliferation and tumorigenicity. We analyzed the expression of the
      human ERas gene in human ES cells by reverse transcription-polymerase chain
      reaction (RT-PCR) and serial analysis of gene expression but could not detect a
      full-length coding transcript. Sequence analysis predicted a premature
      polyadenylation signal for the human ERas transcript, which we confirmed by 3'
      RACE analysis. By RT-PCR, we identified a truncated noncoding transcript in human
      ES cells that is downregulated during differentiation, suggesting conserved
      tissue specificity of the promoter region. Previous reports and expressed
      sequence tag databases indicate that orthologues of this gene are expressed in
      other mammals, including the mouse, dog, and cow, which suggests that it became a
      silenced pseudogene relatively recently in mammalian evolution. In addition to
      the premature polyadenylation site, both the human and chimpanzee ERas genes
      include typical Alu-S retrotransposon insertions that could also influence
      expression at this locus. The lack of ERas expression in human ES cells suggests
      that they could have significantly different tumorigenic properties than mouse ES
      cells.

PMID- 16081665
TI  - Generation of chromosome-specific monoclonal antibodies using in vitro
      differentiated transchromosomic mouse embryonic stem cells.
AB  - Monoclonal antibodies (MoAbs) recognizing lineage- and stage-specific human cell
      surface antigens are valuable reagents for the characterization and isolation of
      various specialized cell populations derived from human embryonic stem cells
      (hESCs). In this report, we examined the use of in vitro differentiated
      transchromosomic mouse embryonic stem cells (TC-ESCs) as immunogens to obtain
      MoAbs against human cell-surface antigens. Immunization of a neural-cell
      population derived from differentiating human chromosome 4 and 11 TC-ESCs
      resulted in two chromosome-specific MoAbs, h4-neural1 and h11-neural1,
      respectively. The staining profiles of differentiated TC-ESCs and human embryonic
      carcinoma cells with these MoAbs were similar to the expression profile of
      nestin, a well-characterized intracellular marker for neural progenitor cells. We
      also described the successful purification and identification of the gene for h4
      neural1 antigen (CD133, 4p15.32) with immunoaffinity chromatography. This
      procedure may have significant utility in generating MoAbs useful for
      understanding the mechanism that regulates the in vitro differentiation of hESCs.

PMID- 16081666
TI  - Gene expression signatures of seven individual human embryonic stem cell lines.
AB  - Identification of molecular components that define a pluripotent human embryonic
      stem cell (hESC) provides the basis for understanding the molecular mechanisms
      regulating the maintenance of pluripotency and induction of differentiation. We
      compared the gene expression profiles of seven genetically independent hESC lines
      with those of nonlineage-differentiated cells derived from each line. A total of
      8,464 transcripts were expressed in all hESC lines. More than 45% of them have no
      yet-known biological function, which indicates that a high number of unknown
      factors contribute to hESC pluripotency. Among these 8,464 transcripts, 280 genes
      were specific for hESCs and 219 genes were more than twofold differentially
      expressed in all hESC lines compared with nonlineage-differentiated cells. They
      represent genes implicated in the maintenance of pluripotency and those involved
      in early differentiation. The chromosomal distribution of these hESC-enriched
      genes showed over-representation in chromosome 19 and under-representation in
      chromosome 18. Although the overall gene expression profiles of the seven hESC
      lines were markedly similar, each line also had a subset of differentially
      expressed genes reflecting their genetic variation and possibly preferential
      differentiation potential. Limited overlap between gene expression profiles
      illustrates the importance of cross-validation of results between different ESC
      lines.

PMID- 16081667
TI  - Transplantation of endothelial progenitor cells accelerates dermal wound healing
      with increased recruitment of monocytes/macrophages and neovascularization.
AB  - Endothelial progenitor cells (EPCs) act as endothelial precursors that promote
      new blood vessel formation and increase angiogenesis by secreting growth factors
      and cytokines in ischemic tissues. These facts prompt the hypothesis that EPC
      transplantation should accelerate the wound-repair process by facilitating
      neovascularization and the production of various molecules related to wound
      healing. In a murine dermal excisional wound model, EPC transplantation
      accelerated wound re-epithelialization compared with the transplantation of
      mature endothelial cells (ECs) in control mice. When the wounds were analyzed
      immunohistochemically, the EPC-transplanted group exhibited significantly more
      monocytes/macrophages in the wound at day 5 after injury than did the EC
      transplanted group. This observation is consistent with enzyme-linked
      immunosorbent assay results showing that EPCs produced in abundance several
      chemoattractants of monocytes and macrophages that are known to play a pivotal
      role in the early phase of wound healing. At day 14 after injury, the EPC
      transplanted group showed a statistically significant increase in vascular
      density in the granulation tissue relative to that of the EC-transplanted group.
      Fluorescence microscopy revealed that EPCs preferentially moved into the wound
      and were directly incorporated into newly formed capillaries in the granulation
      tissue. These results suggest that EPC transplantation will be useful in dermal
      wound repair and skin regeneration, because EPCs both promote the recruitment of
      monocytes/macrophages into the wound and increase neovascularization.

PMID- 16081668
TI  - Essential roles of sphingosine-1-phosphate and platelet-derived growth factor in
      the maintenance of human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) have great potential for use in research and
      regenerative medicine, but very little is known about the factors that maintain
      these cells in the pluripotent state. We investigated the role of three major
      mitogenic agents present in serum--sphingosine-1-phosphate (S1P),
      lysophosphatidic acid (LPA), and platelet-derived growth factor (PDGF)--in
      maintaining hESCs. We show here that although LPA does not affect hESC growth or
      differentiation, coincubation of S1P and PDGF in a serum-free culture medium
      successfully maintains hESCs in an undifferentiated state. Our studies indicate
      that signaling pathways activated by tyrosine kinase receptors act
      synergistically with those downstream from lysophospholipid receptors to maintain
      hESCs in the undifferentiated state. This study is the first demonstration of a
      role for lysophospholipid receptor signaling in the maintenance of stem cell
      pluri-potentiality.

PMID- 16081669
TI  - Human umbilical cord blood progenitors: the potential of these hematopoietic
      cells to become neural.
AB  - The mononuclear fraction from human umbilical cord blood (HUCB) contains a
      significant number of stem/progenitor cells that in theory could be come any cell
      in the body, including neurons. Taking into consideration that
      transdifferentiation would be a very rare event and also knowing that overlapping
      genetic programs for hematopoiesis and neuropoiesis exist, we undertook a
      characterization of the HUCB mononuclear fraction, including analysis of cellular
      subpopulations and their morphology, cell viability, proliferation, and
      expression of neural and hematopoietic antigens. Two cell populations were
      apparent-adherent and floating fractions. The adherent fraction was mainly
      lymphocytes (~53%) expressing hematopoietic antigens. Upon replate, the floating
      population had many cells that expressed stem cell antigens. More of the cells in
      this subfraction expressed neural proteins. Neurotrophin receptors trkB and trkC
      were present in both cell fractions, although expression was higher in the
      floating fraction. Our initial characterization suggests that a subpopulation of
      cells exists within the HUCB mononuclear fraction that seems to have the
      potential to become neural cells, which could then be used in the development of
      cell-based therapies for brain injuries and diseases.

PMID- 16081670
TI  - Flavonoids as a novel class of human organic anion-transporting polypeptide
      OATP1B1 (OATP-C) modulators.
AB  - Flavonoids are a class of polyphenolic compounds widely present in the diet and
      herbal products. The interactions of flavonoids with some major efflux
      transporters [e.g., P-glycoprotein, multidrug resistance-associated protein 1
      (MRP1), and breast cancer resistance protein] have been reported; however, their
      interactions with uptake transporters are largely unknown. Organic anion
      transporting polypeptide OATP1B1 is a liver-specific uptake transporter important
      in hepatic drug disposition. Our objective was to evaluate the effects of 20
      naturally occurring flavonoids, and some of their corresponding glycosides, on
      the uptake of [3H]dehydroepiandrosterone sulfate (DHEAS) in OATP1B1-expressing
      and OATP1B1-negative HeLa cells. Many of the tested flavonoids (including
      biochanin A, genistein, and epigallocatechin-3-gallate) significantly inhibited
      [3H]DHEAS uptake in a concentration-dependent manner in OATP1B1-expressing cells,
      with biochanin A being one of the most potent inhibitors with an IC50 of 11.3 +/-
      3.22 microM. The flavonoids had negligible or small effects in OATP1B1-negative
      cells. Four of the eight pairs of tested flavonoids and their glycosides, namely,
      genistein/genistin, diosmetin/diosmin, epigallocatechin/epigallocatechin-3
      gallate, and quercetin/rutin, exhibited distinct effects on [3H]DHEAS uptake. For
      example, genistin did not inhibit DHEAS uptake, whereas genistein did, and rutin
      stimulated uptake, whereas quercetin had no effect. [3H]Biochanin A uptake was
      similar in OATP1B1-expressing and OATP1B1-negative cells, suggesting that it is
      not a substrate for OATP1B1. A kinetic study revealed that biochanin A inhibited
      [3H]DHEAS uptake in a noncompetitive manner, with a Ki of 10.2 +/- 1.89 microM.
      Taken together, these results indicate that flavonoids are a novel class of
      OATP1B1 modulators, suggesting the potential for diet-drug interactions.

PMID- 16081671
TI  - Prediction of CYP2C9-mediated drug-drug interactions: a comparison using data
      from recombinant enzymes and human hepatocytes.
AB  - The IC50 values of 14 drugs were determined in recombinantly expressed CYP2C9
      (rCYP2C9) and human hepatocytes and the data used to simulate clinical area under
      the plasma concentration-time curve (AUC) changes upon coadministration with
      prototypic CYP2C9 substrates. There was an excellent correlation between IC(50,
      apparent) values determined using diclofenac and naproxen as CYP2C9 substrates
      (r2 = 0.82, p < 0.0001), with values being generally higher in the naproxen
      assay. After correcting for nonspecific binding, the IC(50, unbound) values were
      similar between the assays, for the majority of compounds. Two compounds,
      amiodarone and benzbromarone, demonstrated substrate-specific differences,
      activating naproxen O-demethylase to approximately 250% of control activity at 1
      mM and 1 microM, respectively, while inhibiting diclofenac 4'-hydroxylation with
      IC(50, apparent) values of 3 microM and 0.04 microM, respectively. CYP2C9 IC(50,
      apparent) values generated in human hepatocytes were systematically higher than
      those determined with rCYP2C9. After correcting for nonspecific binding, there
      was an excellent correlation of IC(50, unbound) values generated in the different
      milieu (r2 = 0.88, p < 0.0001). The ratio of inhibitor concentration at the
      entrance to the liver to the inhibition constant ([I]in/Ki) was used to simulate
      clinical deltaAUC changes and compared with that observed in vivo. Where [I]in,
      total/Ki, apparent) was used, there were zero false negatives (observed deltaAUC
      >or=2, predicted deltaAUC <2), eight correct assignations, and seven false
      positives (observed deltaAUC <or=2, predicted deltaAUC >2. Where [I]in,
      unbound/Ki, unbound was used, there was one false negative, 14 correct
      assignations, and zero false positives. In summary, the data presented here
      suggest that for CYP2C9 interactions, the use of total liver inhibitor
      concentrations may indeed avoid false negatives, but more realistic predictions
      may be achieved using unbound liver inhibitor concentrations and unbound in vitro
      inhibition parameters.

PMID- 16081672
TI  - Biotransformation of a GABAA receptor partial agonist in sprague-dawley rats and
      cynomolgus monkeys: identification of two unique N-carbamoyl metabolites.
AB  - The absorption, metabolism, and excretion of N-[3-fluoro-4-[2
      (propylamino)ethoxy]phenyl]-4,5,6,7-tetrahydro-4-oxo-1H-indole-3-carboxamide
      monomethanesulfonate (1), a GABAA receptor partial agonist potentially useful in
      treating generalized anxiety disorder, have been evaluated in both Sprague-Dawley
      rats and cynomolgus monkeys using [14C]1. In both species, mass balance was
      achieved within 48 h postdose, with the majority of drug-related material
      excreted within the feces; the clearance of 1 in each species had both metabolic
      and renal components. In addition to the metabolites produced by aliphatic
      hydroxylation and/or N-dealkylation of 1, two unique metabolites were detected: a
      putative carbamic acid (M7) in rat plasma and monkey bile, and an N-carbamoyl
      glucuronide (M8) in both rat and monkey bile. Metabolite M8 was structurally
      deciphered by liquid chromatographytandem mass spectrometry and NMR, and was
      readily generated in vitro upon incubation of [14C]1 with rat liver microsomes
      fortified with uridine 5'-diphosphoglucuronic acid trisodium salt and alamethicin
      under a CO2 atmosphere. Treatment of M8 with beta-glucuronidase afforded 1
      directly. The presence of M8 in bile and its notable absence from other matrices
      suggests the enterohepatic cycling of 1 via M8. Although the structure of M7 was
      not elucidated unequivocally due to its inability to be formed in vitro and its
      minimal absolute quantities in limited biological matrices, data herein clearly
      support its structural rationalization. Furthermore, since M7 is the precursor of
      M8, detection of M8 is indirect evidence of its existence. It is proposed that M7
      arises from an equilibrium between 1 and dissolved CO2-equivalents both in vivo
      and in vitro, similar to carbamino bonds observed in hemoglobin and certain amino
      acids, respectively.

PMID- 16081673
TI  - Importance of CYP2D3 in polymorphism of diazepam p-hydroxylation in rats.
AB  - Diazepam was metabolized to three primary metabolites, 3-hydroxy-diazepam, N
      desmethyl-diazepam, and p-hydroxy-diazepam. Our previous studies reported
      metabolic position-specific inter- or intrastrain differences in diazepam
      metabolism among Sprague-Dawley, Brown Norway, Dark Agouti, and Wistar rats.
      Especially, there were marked ( approximately 300 fold) inter- or intrastrain
      differences in diazepam p-hydroxylation activity at low concentration of
      substrate. In this study, we investigated the enzyme that catalyzes diazepam p
      hydroxylation. The activity toward diazepam p-hydroxylation was inhibited by anti
      cytochrome P450 2D (CYP2D) antibody, suggesting that this activity was catalyzed
      by CYP2D isoforms. Comparing the expression levels of the CYP2D subfamily in
      liver microsomes from various strains of rats using anti-CYP2D2 antibody, we
      found that there was a band of protein that was consistent with the phenotype of
      diazepam p-hydroxylation. N-terminal amino acid sequences of the specific protein
      exactly corresponded to those of CYP2D3, indicating that CYP2D3 might be involved
      in diazepam p-hydroxylation. Moreover, using rat CYP2D isoforms expressed in
      yeast, we tested CYP2Ds to catalyze diazepam p-hydroxylation. CYP2D1 and CYP2D2
      practically did not participate in diazepam metabolism. On the other hand,
      diazepam p-hydroxylation was catalyzed by CYP2D3. CYP2D4 had high activity toward
      diazepam N-desmethylation, but not p-hydroxylation. In conclusion, the
      polymorphic expression of CYP2D3 caused the inter- or intrastrain differences in
      diazepam p-hydroxylation among rat strains or individuals.

PMID- 16081674
TI  - Agonist-directed trafficking of response by endocannabinoids acting at CB2
      receptors.
AB  - This study examined the ability of the endocannabinoids 2-arachidonoyl glycerol
      (2-AG) and noladin ether as well as the synthetic cannabinoid CP-55,940 [(-)-cis
      3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)
      cyclohexanol] to regulate three intracellular effectors via CB2 receptors in
      transfected Chinese hamster ovary cells. Although the three agonists regulate all
      effectors with equivalent efficacy, the rank order of potencies differs depending
      on which effector is evaluated. Noladin ether and CP-55,940 most potently inhibit
      adenylyl cyclase, requiring higher concentrations to stimulate the extracellular
      signal-regulated kinase subgroup of the mitogen-activated protein kinases
      (extracellular signal-regulated kinase-mitogen-activated protein kinase; ERK
      MAPK) and Ca(2+)-transients. In contrast, 2-AG most potently activates ERK-MAPK,
      necessitating greater concentrations to inhibit adenylyl cyclase and even higher
      amounts to stimulate Ca(2+)-transients. Endocannabinoids also seem to be more
      "efficient" agonists at CB2 receptors relative to synthetic agonists. 2-AG and
      noladin ether require occupancy of less than one-half the number of receptors to
      produce comparable regulation of adenylyl cyclase and ERK-MAPK, relative to the
      synthetic cannabinoid CP-55,940. The CB2 antagonist 6-iodo-2-methyl-1-[2-(4
      morpholinyl)-ethyl]-1H-indol-3-yl](4-methoxyphenyl)-methanone (AM630) reverses
      the actions of all agonists except Ca(2+)-transient stimulation by 2-AG. However,
      the effect of 2-AG on Ca(2+)-transients is attenuated by a second CB2 antagonist
      N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3
      methylphenyl)-1-(4-methylbenzyl)-1-pyrazole-3-carboxamide (SR144528). This
      suggests that 2-AG stimulates Ca(2+)-transients by binding to sites on CB2
      receptors distinct from those occupied by AM630 and the other cannabinoids
      examined. Agonists produce no effects in pertussis toxin-treated cells. In
      summary, cannabinoid agonists distinctly bind to CB2 receptors and display
      different rank order of potencies and fractional receptor occupancies for
      regulation of intracellular effectors. These data provide direct evidence for
      agonist-directed trafficking of response by endocannabinoids acting at CB2
      receptors.

PMID- 16081675
TI  - Peroxynitrite-induced mitochondrial and endonuclease-mediated nuclear DNA damage
      in acetaminophen hepatotoxicity.
AB  - Intracellular sources of peroxynitrite formation and potential targets for this
      powerful oxidant and nitrating agent have not been identified after acetaminophen
      (AAP) overdose. Therefore, we tested the hypothesis that peroxynitrite generated
      in mitochondria may be responsible for mitochondrial DNA (mtDNA) and nuclear DNA
      (nDNA) damage. C3Heb/FeJ mice were treated with 300 mg/kg AAP and monitored for
      up to 12 h. Loss of mtDNA (assayed by slot blot hybridization) and substantial
      nDNA fragmentation (evaluated by anti-histone enzyme-linked immunosorbent assay,
      terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and agarose
      gel electrophoresis) were observed as early as 3 h after AAP overdose. Analysis
      of nitrotyrosine protein adducts in subcellular fractions established that
      peroxynitrite was generated predominantly in mitochondria beginning at 1 h after
      AAP injection. Delayed treatment with a bolus dose of glutathione (GSH)
      accelerated the recovery of mitochondrial glutathione, which then effectively
      scavenged peroxynitrite. However, mtDNA loss was only partially prevented.
      Despite the absence of nitrotyrosine adducts in the nucleus after AAP overdose,
      nDNA damage was almost completely eliminated with GSH administration. A direct
      comparison of nDNA damage after AAP overdose with nDNA fragmentation during tumor
      necrosis factor receptor-mediated apoptosis showed similar DNA ladders on agarose
      gels but quantitatively different results in three other assays. We conclude that
      peroxynitrite may be partially responsible for mtDNA loss but is not directly
      involved in nDNA damage. In contrast, nDNA fragmentation after AAP overdose is
      not caused by caspase-activated DNase but most likely by other intracellular
      DNase(s), whose activation is dependent on the mitochondrial oxidant stress and
      peroxynitrite formation.

PMID- 16081676
TI  - Functional analysis of organic cation transporter 3 expressed in human placenta.
AB  - The aim of this study is to investigate the placental transport mechanism of
      cationic compounds by comparison of the uptake of an organic cation into human
      placental basal membrane vesicles (BLMVs) with that into organic cation
      transporter 3 (OCT3)-expressing cells. Reverse transcription-polymerase chain
      reaction analysis demonstrated that OCT3 is the only OCT isoform expressed in the
      human placenta. The function of OCT3 was investigated by measuring the uptake of
      1-methyl-4-phenylpyridinium (MPP(+)) into human embryonic kidney (HEK)293 cells
      stably expressing OCT3 (HEK/OCT3 cells). The OCT3-mediated uptake of MPP(+) was
      sodium- and chloride-independent and saturable, with a Michaelis constant (K(m))
      of 82.5 microM. The OCT3-mediated uptake was inhibited by various cationic drugs
      in a concentration-dependent manner but not by anionic compounds, such as p
      aminohippuric acid and captopril, or a zwitterion, carnitine. Western blotting
      analysis of membrane vesicles prepared from human term placenta revealed that
      OCT3 is expressed only in BLMVs but not in microvillous membrane vesicles. The
      uptake of MPP(+) into BLMVs was membrane potential-dependent and saturable, with
      a K(m) value of 51.8 muM, which is similar to that in HEK293/OCT3 cells. The
      inhibitory spectrum of various compounds on MPP(+) uptake by BLMVs was also
      similar to that in HEK293/OCT3 cells. These results suggest that OCT3 is
      expressed on the basal membrane of human trophoblast cells and plays an important
      role in the placental transport of cationic compounds.

PMID- 16081677
TI  - Curcumin suppresses interleukin 1beta-mediated microsomal prostaglandin E
      synthase 1 by altering early growth response gene 1 and other signaling pathways.
AB  - Curcumin (diferuloylmethane) is one of the phytophenolic compounds found in the
      turmeric plant with anti-inflammatory and anticarcinogenic activities. One
      possible mechanism for these activities is the inhibition of prostaglandin (PG)
      E(2) formation. In this study and other reports, curcumin suppresses interleukin
      1beta-induced formation of prostaglandin E(2) in a concentration-dependent
      manner. Interleukin-1beta-induced microsomal prostaglandin E synthase 1 (mPGES-1)
      and cyclooxygenase-2 were attenuated by curcumin at the protein and mRNA levels,
      but a more dramatic inhibition of mPGES-1 expression was observed at lower
      concentrations of curcumin in A549 human lung epithelial cells. The inhibition of
      mPGES-1 expression by curcumin shifted the arachidonic acid profile from PGE(2)
      to PGF(2alpha) and 6-keto-PGF(1alpha) as major metabolites. The expression of
      early growth response gene 1 (EGR-1), a key transcription factor of cytokine
      induced mPGES-1, was inhibited by curcumin. Incubation with siRNA for EGR-1
      inhibited interleukin (IL)-1beta-induced mPGES-1, and the controlled expression
      of EGR-1 increased the mPGES-1 expression. Several proinflammatory signaling
      molecules, such as nuclear factor kappaB (NF-kappaB) and mitogen-activated
      protein kinases, are also known to affect curcumin-regulated gene expression.
      Curcumin inhibited IkappaBalpha phosphorylation and degradation and thus reduced
      the expression of mPGES-1. Curcumin suppressed cytokine-induced mPGES-1 by
      inhibiting phosphorylation of Jun N-terminal kinase (JNK)1/2. However, EGR-1
      expression was suppressed by lower concentrations of curcumin, as compared with
      JNK1/2 and IkappaBalpha. These results indicate that curcumin inhibits IL-1beta
      induced PGE(2) formation by inhibiting the expression of mPGES-1 that is mediated
      by suppression of EGR-1 expression as well as NF-kappaB and JNK1/2.

PMID- 16081678
TI  - Prostaglandin E2 enhances neurotrophin-4 production via EP3 receptor in human
      keratinocytes.
AB  - Atopic dermatitis is characterized by increased skin innervation. The expression
      of neurotrophin-4 is enhanced in the epidermal keratinocytes of lesions with
      atopic dermatitis and may be related to hyperinnervation in these lesions.
      Prostaglandin E(2) (PGE(2)) levels are increased in lesions with atopic
      dermatitis; thus, PGE(2) may be involved in the development of this disease. We
      examined the in vitro effects of PGE(2) on neurotrophin-4 production in human
      keratinocytes. PGE(2) and EP1/EP3 agonist sulprostone increased neurotrophin-4
      secretion and mRNA levels without altering its mRNA stability. Antisense Sp1
      oligodeoxynucleotide and Sp1 inhibitor mithramycin A suppressed PGE(2) and
      sulprostone-induced neurotrophin-4 expression, indicating the requirement for Sp1
      for expression. PGE(2) or sulprostone markedly enhanced the phosphorylation, DNA
      binding, and transcriptional activity of Sp1 and modestly increased Sp1 mRNA and
      protein levels. PGE(2) or sulprostone induced the membrane translocation of
      protein kinase Calpha and the phosphorylation of extracellular signal-regulated
      kinase (ERK). PGE(2)-induced increases in neurotrophin-4 expression, Sp1
      transcriptional and DNA-binding activity, Sp1 mRNA and protein levels, and ERK
      phosphorylation were suppressed by antisense EP3 oligodeoxynucleotide, inhibitors
      of phosphatidylinositol-specific phospholipase C, conventional protein kinase C,
      and mitogen-activated protein kinase/ERK kinase 1 (MEK1). These results suggest
      that PGE(2) enhances neurotrophin-4 production by activating Sp1 via the
      EP3/phosphatidylinositol-specific phospholipase C/protein kinase Calpha/MEK1/ERK
      pathway. PGE(2) may promote innervation in skin lesions with atopic dermatitis
      via the induction of neurotrophin-4.

PMID- 16081679
TI  - General anesthetic-induced channel gating enhancement of 5-hydroxytryptamine type
      3 receptors depends on receptor subunit composition.
AB  - 5-Hydroxytryptamine (serotonin) (5-HT) type 3 (5-HT(3)) receptors are members of
      an anesthetic-sensitive superfamily of Cys-loop ligand-gated ion channels that
      can be formed as homomeric 5-HT(3A) or heteromeric 5-HT(3AB) receptors. When the
      efficacious agonist 5-HT is used, the inhaled anesthetics halothane and
      chloroform (at clinically relevant concentrations) significantly reduce the
      agonist EC(50) for 5-HT(3A) receptors but not for 5-HT(3AB) receptors. In the
      present study, we used dopamine (DA), a highly inefficacious agonist for 5-HT(3)
      receptors, to determine whether the difference in sensitivity between 5-HT(3A)
      and 5-HT(3AB) receptors to the potentiating effects of halothane and chloroform
      is due to differential modulation of agonist affinity, channel gating, or both.
      Using the two-electrode voltage-clamp technique with 5-HT(3A) and 5-HT(3AB)
      receptors expressed in Xenopus oocytes, we found that chloroform and halothane
      enhanced currents evoked by receptor-saturating concentrations of DA for both
      receptor subtypes in a concentration-dependent manner but that the magnitude of
      enhancement was substantially greater for 5-HT(3A) receptors than for 5-HT(3AB)
      receptors. Isoflurane induced only a small enhancement of currents evoked by
      receptor-saturating concentrations of DA for 5-HT(3A) receptors and no
      enhancement for 5-HT(3AB) receptors. For both receptor subtypes, none of the
      three test anesthetics significantly altered the agonist EC(50) for DA, implying
      that these anesthetics do not affect agonist binding affinity. Our results show
      that chloroform, halothane, and (to a much lesser degree) isoflurane enhance
      channel gating for 5-HT(3A) receptors and that the incorporation of 5-HT(3B)
      subunits to produce heteromeric 5-HT(3AB) receptors markedly attenuates the
      ability of these anesthetics to enhance channel gating.

PMID- 16081680
TI  - Handling of the homocysteine S-conjugate of methylmercury by renal epithelial
      cells: role of organic anion transporter 1 and amino acid transporters.
AB  - Recently, the activity of the organic anion transporter 1 (OAT1) protein has been
      implicated in the basolateral uptake of inorganic mercuric species in renal
      proximal tubular cells. Unfortunately, very little is known about the role of
      OAT1 in the renal epithelial transport of organic forms of mercury, such as
      methylmercury (CH(3)Hg(+)). Homocysteine (Hcy) S-conjugates of methylmercury [(S)
      (3-amino-3-carboxypropylthio)(methyl)mercury (CH(3)Hg-Hcy)] have been identified
      recently as being potentially important biologically relevant forms of mercury.
      Thus, the present study was designed to characterize the transport of CH(3)Hg-Hcy
      in Madin-Darby canine kidney (MDCK) cells (which are derived from the distal
      nephron) that were transfected stably with the human isoform of OAT1 (hOAT1).
      Data on saturation kinetics, time dependence, substrate specificity, and
      temperature dependence demonstrated that CH(3)Hg-Hcy is a transportable substrate
      of hOAT1. However, substrate-specificity data from the control MDCK cells also
      showed that CH(3)Hg-Hcy is a substrate of one or more transporter(s) that is/are
      not hOAT1. Additional findings indicated that at least one amino acid transport
      system was probably responsible for this transport. It is noteworthy that the
      activity of amino acid transporters accounted for the greatest level of uptake of
      CH(3)Hg-Hcy in the hOAT1-expressing cells. Furthermore, rates of survival of the
      hOAT1-transfected MDCK cells were significantly lower than those of corresponding
      control MDCK cells when they were exposed to cytotoxic concentrations of CH(3)Hg
      Hcy. Collectively, the present data indicate that CH(3)Hg-Hcy is a transportable
      substrate of OAT1 and amino acid transporters and, thus, is probably a
      transportable mercuric species taken up in vivo by proximal tubular epithelial
      cells.

PMID- 16081681
TI  - Anti-inflammatory effects of inhibiting the amine oxidase activity of
      semicarbazide-sensitive amine oxidase.
AB  - Human semicarbazide-sensitive amine oxidase (SSAO) or vascular adhesion protein-1
      (VAP-1) is a copper-containing amine oxidase (AOC3, EC 1.4.3.6) that has both
      enzymatic and adhesive function. SSAO catalyzes the oxidative deamination of
      primary amines, resulting in the formation of the corresponding aldehyde and
      release of hydrogen peroxide and ammonia. Membrane-bound SSAO is an inflammation
      inducible endothelial cell adhesion molecule that mediates the interaction
      between leukocytes and activated endothelial cells in inflamed vessels. Both the
      direct adhesive and enzymatic functions seem to be involved in the adhesion
      cascade. LJP 1207 [N'-(2-phenyl-allyl)-hydrazine hydrochloride] is a potent
      (human SSAO IC(50) = 17 nM), selective, and orally available SSAO inhibitor that
      blocks both the enzymatic and adhesion functions of SSAO/VAP-1. In a mouse model
      of ulcerative colitis, LJP 1207 significantly reduces mortality, loss of body
      weight, and colonic cytokine levels. Quantitative histopathological assessment of
      colitis activity in this model showed a highly significant suppression of
      inflammation, injury, and ulceration scores in the animals treated with the
      SSAO/VAP-1 inhibitor. LJP 1207 also reduced serum levels of tumor necrosis factor
      alpha and interleukin 6 in lipopolysaccharide (LPS)-challenged mice and prolonged
      survival post-LPS-induced endotoxemia. Therapeutic and prophylactic
      administration of LJP 1207 in the rat carrageenan footpad model also markedly
      inhibited swelling and inflammation. Overall, the data suggest that small
      molecule SSAO/VAP-1 inhibitors may provide clinical benefit in the treatment of
      acute and chronic inflammatory diseases.

PMID- 16081682
TI  - Human U251 glioma cell proliferation is suppressed by HET0016 [N-hydroxy-N'-(4
      butyl-2-methylphenyl)formamidine], a selective inhibitor of CYP4A.
AB  - We have previously reported that HET0016 [N-hydroxy-N'-(4-butyl-2
      methylphenyl)formamidine], a selective inhibitor of CYP4A and thus 20-HETE (20
      hydroxyeicosatetraenoic acid) synthesis, inhibits endothelial cell proliferation
      and decreases angiogenesis induced by human glioma cell U251. A stable 20-HETE
      agonist, WIT003 [20-hydroxyeicosa-5(Z),14(Z)-dienoic acid (1 microM)], increased
      U251 cell proliferation from 3.9- to 4.8-folds from T(0) (time of the treatment).
      We examined the effects of HET0016 on the growth of U251. HET0016 inhibited U251
      basal cell proliferation in a dose-dependent manner. 10 microM HET0016 suppressed
      56% of U251 proliferation and significantly increased the proportions of the
      cells arrested in the G(0)/G(1) phase of the cell cycle. Exposure to HET0016 (as
      early as 4 h) reduced protein tyrosine and p42/p44 MAPK (mitogen-activated
      protein kinase) phosphorylation. Furthermore, HET0016 significantly inhibited the
      U251 proliferation and phosphorylation of both the epidermal growth factor (EGF)
      receptor and p42/p44 MAPK induced by EGF. CYP4A mRNA and proteins were both
      present in U251. This suggests that HET0016 inhibited U251 proliferation by
      inhibiting 20-HETE synthesis. However, U251 did not synthesize 20-HETE in the
      presence of arachidonic acid. This implies that HET0016 suppresses U251
      proliferation by mechanisms that are not yet clear but may involve activities
      other than inhibition of 20-HETE synthesis. We concluded that HET0016 may be the
      prototype of novel compounds that suppress human glioma cell proliferation.

PMID- 16081683
TI  - Lack of Il12rb2 signaling predisposes to spontaneous autoimmunity and malignancy.
AB  - The interleukin-12 receptor beta2 (Il12rb2) gene is silenced in tumor cells from
      different human B-cell malignancies as opposed to their normal counterparts. It
      was hypothesized that this silencing allows neoplastic B cells to escape the
      control exerted by IL-12 on their growth. The aim of this study was to
      investigate whether targeted inactivation of the Il12rb2 gene in mice resulted
      into increased susceptibility to spontaneous tumor formation and immunopathology.
      Il12rb2 gene-deficient animals developed in the first year of life immune-complex
      mesangial glomerulonephritis with serum antinuclear antibodies. In older animals,
      multiorgan lymphoid infiltrates with features of vasculitis and Sjogren syndrome
      were detected in association with systemic B- and T-cell activation. In half of
      aged animals, lymph node plasmacytoma or lung carcinoma was observed. A mechanism
      for spontaneous development of autoimmune pathology and B-cell tumors is
      suggested by a strong IL-6 up-regulation detected in splenocytes and lymphoid
      infiltrates associated with oligoclonal B-cell expansion. The emergence of lung
      tumors may likely be attributed to an interferon-gamma (IFN-gamma) deficiency
      secondary to lack of IL-12 signaling. The development of autoimmunity,
      lymphoproliferation, and B-cell tumors in Il12rb2 knockout (KO) mice suggests
      that IL-12 functions physiologically to restrain aberrant B-cell activation.

PMID- 16081684
TI  - Altered gene expression in myeloproliferative disorders correlates with
      activation of signaling by the V617F mutation of Jak2.
AB  - We identified 13 new gene expression markers that were elevated and one marker,
      ANKRD15, that was down-regulated in patients with polycythemia vera (PV). These
      14 markers, as well as the previously described PRV1 and NF-E2, exhibited the
      same gene expression alterations also in patients with exogenously activated
      granulocytes due to sepsis or granulocyte colony-stimulating factor (G-CSF)
      treatment. The recently described V617F mutation in the Janus kinase 2 (JAK2)
      gene allows defining subclasses of patients with myeloproliferative disorders
      based on the JAK2 genotype. Patients with PV who were homozygous or heterozygous
      for JAK2-V617F exhibited higher levels of expression of the 13 new markers, PRV1,
      and NF-E2 than patients without JAK2-V617F, whereas ANKRD15 was down-regulated in
      these patients. Our results suggest that the alterations in expression of the
      markers studied are due to the activation of the Jak/signal transducer and
      activator of transcription (STAT) pathway through exogenous stimuli (sepsis or G
      CSF treatment), or endogenously through the JAK2-V617F mutation.

PMID- 16081685
TI  - MEK kinase 1 activity is required for definitive erythropoiesis in the mouse
      fetal liver.
AB  - Mitogen-activated protein kinase/extracellular signal to regulated kinase (MEK)
      kinase 1 (MEKK1) is a c-Jun N-terminal kinase (JNK) activating kinase known to be
      implicated in proinflammatory responses and cell motility. Using mice deficient
      for MEKK1 kinase activity (Mekk1(DeltaKD)) we show a role for MEKK1 in definitive
      mouse erythropoiesis. Although Mekk1(DeltaKD) mice are alive and fertile on a 129
      x C57/BL6 background, the frequency of Mekk1(DeltaKD) embryos that develop past
      embryonic day (E) 14.5 is dramatically reduced when backcrossed into the C57/BL6
      background. At E13.5, Mekk1(DeltaKD) embryos have normal morphology but are
      anemic due to failure of definitive erythropoiesis. When Mekk1(DeltaKD) fetal
      liver cells were transferred to lethally irradiated wild-type hosts, mature red
      blood cells were generated from the mutant cells, suggesting that MEKK1 functions
      in a non-cell-autonomous manner. Based on immunohistochemical and hemoglobin
      chain transcription analysis, we propose that the failure of definitive
      erythropoiesis is due to a deficiency in enucleation activity caused by
      insufficient macrophage-mediated nuclear DNA destruction.

PMID- 16081686
TI  - A redox signature score identifies diffuse large B-cell lymphoma patients with a
      poor prognosis.
AB  - Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease in which
      approximately 40% of the patients respond well to current chemotherapy, but the
      prognosis for the other 60% is poor. The Leukemia/Lymphoma Molecular Profiling
      Project (LLMPP) used microarray technology to define a molecular profile for each
      of 240 patients with DLBCL and develop a molecular outcome predictor score that
      accurately predicted patient survival. Data from our laboratory and others
      suggest that alterations in antioxidant defense enzyme levels and redox
      environment can be oncogenic and affect the response to glucocorticoid treatment,
      one of the components of combination chemotherapy regimens for lymphoma. The goal
      of the current study was to reanalyze the LLMPP microarray data to determine
      whether the levels of antioxidant defense enzymes and redox proteins were
      correlated with prognosis in DLBCL. We found that patients with DLBCL with the
      worst prognosis, according to the outcome predictor score, had decreased
      expression of catalase, glutathione peroxidase, manganese superoxide dismutase,
      and VDUP1, a protein that inhibits thioredoxin activity. The data suggest that
      the patients with the worst prognosis combine a decrease in antioxidant defense
      enzyme expression with an increase in thioredoxin system function (the redox
      signature score).

PMID- 16081687
TI  - The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and
      acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic
      lymphocytic leukemia.
AB  - Activating mutations in tyrosine kinases have been identified in hematopoietic
      and nonhematopoietic malignancies. Recently, we and others identified a single
      recurrent somatic activating mutation (JAK2V617F) in the Janus kinase 2 (JAK2)
      tyrosine kinase in the myeloproliferative disorders (MPDs) polycythemia vera,
      essential thrombocythemia, and myeloid metaplasia with myelofibrosis. We used
      direct sequence analysis to determine if the JAK2V617F mutation was present in
      acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML)/atypical
      chronic myelogenous leukemia (aCML), myelodysplastic syndrome (MDS), B-lineage
      acute lymphoblastic leukemia (ALL), T-cell ALL, and chronic lymphocytic leukemia
      (CLL). Analysis of 222 patients with AML identified JAK2V617F mutations in 4
      patients with AML, 3 of whom had a preceding MPD. JAK2V617F mutations were
      identified in 9 (7.8%) of 116 CMML/a CML samples, and in 2 (4.2%) of 48 MDS
      samples. We did not identify the JAK2V617F disease allele in B-lineage ALL (n =
      83), T-cell ALL (n = 93), or CLL (n = 45). These data indicate that the JAK2V617F
      allele is present in acute and chronic myeloid malignancies but not in lymphoid
      malignancies.

PMID- 16081688
TI  - MN1-TEL myeloid oncoprotein expressed in multipotent progenitors perturbs both
      myeloid and lymphoid growth and causes T-lymphoid tumors in mice.
AB  - The MN1-TEL (meningioma 1-translocation-ETS-leukemia) fusion oncoprotein is the
      product of the t(12;22)(p13;q11) in human myeloid leukemia consisting of N
      terminal MN1 sequences, a transcriptional coactivator, fused to C-terminal TEL
      sequences, an E26-transformation-specific (ETS) transcription factor. To analyze
      the role of MN1-TEL in leukemogenesis, we created a site-directed transgenic
      (knock-in) mouse model carrying a conditional MN1-TEL transgene under the control
      of the Aml1 regulatory sequences. After induction, MN1-TEL expression was
      detected in both myeloid and lymphoid cells. Activation of MN1-TEL expression
      enhanced the repopulation ability of myeloid progenitors in vitro as well as
      partially inhibited their differentiation in vivo. MN1-TEL also promoted the
      proliferation of thymocytes while it blocked their differentiation from CD4-/CD8-
      to CD4+/CD8+ in vivo. After long latency, 30% of the MN1-TEL-positive mice
      developed T-lymphoid tumors. This process was accelerated by N-ethyl-N
      nitrosourea-induced mutations. MN1-TEL-positive T-lymphoid tumors showed elevated
      expression of the Notch-1, Hes-1, c-Myc, and Lmo-2 genes while their Ink4a/pRB
      and Arf/p53 pathways were impaired, suggesting that these alterations
      cooperatively transform T progenitors. We conclude that MN1-TEL exerts its
      nonlineage-specific leukemogenic effects by promoting the growth of primitive
      progenitors and blocking their differentiation, but cooperative mutations are
      necessary to fully induce leukemic transformation.

PMID- 16081689
TI  - Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple
      myeloma.
AB  - Mutation of p53 is a rare event in multiple myeloma, but it is unknown if p53
      signaling is functional in myeloma cells, and if targeted nongenotoxic activation
      of the p53 pathway is sufficient to kill tumor cells. Here, we demonstrate that
      treatment of primary tumor samples with a small-molecule inhibitor of the p53
      murine double minute 2 (MDM2) interaction increases the level of p53 and induces
      p53 targets and apoptotic cell death. Significantly, given the importance of the
      bone marrow microenvironment for the support and drug resistance of myeloma
      cells, tumor cells undergo effective apoptosis also in the presence of stromal
      cells, which themselves appear to tolerate exposure to nutlin-3. The in vitro
      toxicity of nutlin-3 was similar to that of the genotoxic drug melphalan. Because
      nutlin-mediated p53 activation is not dependent on DNA damage, MDM2 antagonists
      may help to avoid or reduce the severe genotoxic side effects of chemotherapeutic
      agents currently used to treat multiple myeloma. Therefore, MDM2 antagonists may
      offer a new treatment option for this disease.

PMID- 16081690
TI  - Human CD8+ T cells store CXCR1 in a distinct intracellular compartment and up
      regulate it rapidly to the cell surface upon activation.
AB  - Activation and subsequent differentiation of naive CD8+ T cells lead to the
      development of memory subsets with distinct homing and effector capacities. On
      nonlymphoid homing subsets, expression of "inflammatory" chemokine receptors
      (such as CXCR3, CCR5, CX3CR1, and CXCR1) is believed to promote migration into
      sites of infection/inflammation. Here we show that CXCR1 can be up-regulated to
      the cell surface within minutes of activating human CD8+ T cells. No concurrent
      up-regulation of other inflammatory chemokine receptors was observed. Up
      regulation of CXCR1 preferentially occurred on central memory CD8+ T cells-that
      is, cells with a lymph node homing phenotype-and was functionally relevant.
      Immunofluorescence microscopy showed CXCR1 to be present in intracellular
      vesicles that do not significantly colocalize with perforin, RANTES (regulated
      upon activation normal T cell expressed and secreted), or the lysosomal marker
      CD63. By contrast, partial colocalization with the Golgi marker GM130, the
      constitutive secretory pathway marker beta2-microglobulin, and the early endosome
      marker EEA1 was observed. Up-regulation of CXCR1 did not occur after T-cell
      receptor cross-linking. By contrast, supernatants from activated neutrophils, but
      not from monocytes or dendritic cells, induced its up-regulation. These results
      suggest that CD8+ T cells can rapidly adapt their homing properties by mobilizing
      CXCR1 from a distinct intracellular compartment.

PMID- 16081691
TI  - Potential approach to immunotherapy of chronic lymphocytic leukemia (CLL):
      enhanced immunogenicity of CLL cells via infection with vectors encoding for
      multiple costimulatory molecules.
AB  - Chronic lymphocytic leukemia (CLL) is a disease of CD5(+) B lymphocytes
      (designated as CLL cells) that are inefficient antigen-presenting cells. Their
      poor ability to present antigens to the T cells, largely due to an inadequate
      costimulatory capacity, is manifested as a failure to stimulate proliferation of
      both allogeneic and autologous T cells. We have investigated the ability of in
      vitro manipulated CLL cells, via hyperexpression of a triad of costimulatory
      molecules (B7-1, intercellular adhesion molecule 1 [ICAM-1], and leukocyte
      function-associated antigen 3 [LFA-3], designated TRICOM), to stimulate effective
      antitumor T-cell responses. A recombinant modified vaccinia virus strain Ankara
      (MVA), which is a highly attenuated, replication-impaired virus variant, was
      successfully used to infect and deliver the simultaneous expression of the 3
      human costimulatory molecules in TRICOM on the surface of the CLL cells.
      Proliferation of allogeneic and autologous T cells was observed when MVA-TRICOM
      infected CLL cells were used as stimulators in proliferation assays. Cytotoxic T
      lymphocytes, generated in vitro by stimulation of autologous T cells with MVA
      TRICOM-infected CLL cells, showed cytotoxicity against unmodified/uninfected CLL
      cells. Therefore, our findings suggest that the use of CLL cells infected ex vivo
      with MVA-TRICOM or direct injection of MVA-TRICOM in patients with CLL has
      potential for the immunotherapy of CLL.

PMID- 16081692
TI  - The Ig-ITIM superfamily member PECAM-1 regulates the "outside-in" signaling
      properties of integrin alpha(IIb)beta3 in platelets.
AB  - Previous studies have implicated the immunoglobulin (Ig)-immunoreceptor tyrosine
      based inhibitory motif (ITIM) superfamily member platelet endothelial cell
      adhesion molecule-1 (PECAM-1) in the regulation of integrin function. While PECAM
      1 has been demonstrated to play a role as an inhibitory coreceptor of
      immunoreceptor tyrosine-based activation motif (ITAM)-associated Fcgamma receptor
      IIa (FcgammaRIIa) and glycoprotein VI (GPVI)/FcR gamma-chain signaling pathways
      in platelets, its physiologic role in integrin alpha(IIb)beta3-mediated platelet
      function is unclear. In this study, we investigate the functional importance of
      PECAM-1 in murine platelets. Using PECAM-1-deficient mice, we show that the
      platelets have impaired "outside-in" integrin alpha(IIb)beta3 signaling with
      impaired platelet spreading on fibrinogen, failure to retract fibrin clots in
      vitro, and reduced tyrosine phosphorylation of focal adhesion kinase p125
      (125FAK) following integrin alpha(IIb)beta3-mediated platelet aggregation. This
      functional integrin alpha(IIb)beta3 defect could not be attributed to altered
      expression of integrin alpha(IIb)beta3. PECAM-1-/- platelets displayed normal
      platelet alpha granule secretion, normal platelet aggregation to protease
      activated receptor-4 (PAR-4), adenosine diphosphate (ADP), and calcium ionophore,
      and static platelet adhesion. In addition, PECAM-1-/- platelets displayed normal
      "inside-out" integrin alpha(IIb)beta3 signaling properties as demonstrated by
      normal agonist-induced binding of soluble fluoroscein isothiocyanate (FITC)
      fibrinogen, JON/A antibody binding, and increases in cytosolic-free calcium and
      inositol (1,4,5)P3 triphosphate (IP3) levels. This study provides direct evidence
      that PECAM-1 is essential for normal integrin alpha(IIb)beta3-mediated platelet
      function and that disruption of PECAM-1 induced a moderate "outsidein" integrin
      alpha(IIb)beta3 signaling defect.

PMID- 16081693
TI  - Extracellular KIT receptor mutants, commonly found in core binding factor AML,
      are constitutively active and respond to imatinib mesylate.
AB  - Multiple genetic alterations are required to induce acute myelogenous leukemia
      (AML). Mutations in the extracellular domain of the KIT receptor are almost
      exclusively found in patients with AML carrying translocations or inversions
      affecting members of the core binding factor (CBF) gene family and correlate with
      a high risk of relapse. We demonstrate that these complex insertion and deletion
      mutations lead to constitutive activation of the KIT receptor, which induces
      factor-independent growth of interleukin-3 (IL-3)-dependent cells. Mutation of
      the evolutionary conserved amino acid D419 within the extracellular domain was
      sufficient to constitutively activate the KIT receptor, although high expression
      levels were required. Dose-dependent growth inhibition and apoptosis were
      observed using either the protein tyrosine kinase inhibitor imatinib mesylate
      (STI571, Gleevec) or by blocking the phosphoinositide-3-kinase (PI3K)-AKT
      pathway. Our data show that the addition of kinase inhibitors to conventional
      chemotherapy might be a new therapeutic option for CBF-AML expressing mutant KIT.

PMID- 16081694
TI  - Heterogeneity of engrafted bone-lining cells after systemic and local
      transplantation.
AB  - The outcome of various osteoprogenitor-cell transplantation protocols was
      assessed using Col1a1-GFP reporter transgenic mice. The model requires the
      recipient mice to undergo lethal total body irradiation (TBI) followed by rescue
      with whole bone marrow. When the mice are rescued with total bone marrow from a
      Col1a1-GFP transgenic mouse, green fluorescence protein (GFP)-positive donor
      cells can be observed on most endosteal and trabecular bone surfaces. Although
      the cells express an osteoblast-restricted GFP, they fail to progress to
      osteocytes, do not form a mineralized matrix, and do not generate bone nodules in
      vitro. However when calvarial progenitor cells derived from the same transgenic
      mice are injected into the bone marrow space, osteogenesis by the donor cells is
      observed. Using different GFP colors that distinguish the donor and recipient
      osteoblasts, commingling of the 2 cells types is observed along the mineralizing
      osteoblast surface as well as within the osteocyte population of the endosteal
      bone. Despite the ability of the injected progenitor cells to produce bone within
      the injected bone, they lack the ability to form mineralized bone nodules when
      explanted to primary osteoblast culture. These reagents and imaging protocols
      will be useful in evaluating other cells having a better progenitor potential
      than calvarial-derived stromal cells.

PMID- 16081695
TI  - Vitamin K epoxide reductase significantly improves carboxylation in a cell line
      overexpressing factor X.
AB  - Previously we reported that we could increase the fraction of carboxylated factor
      X by reducing the affinity of the propeptide for its binding site on human gamma
      glutamyl carboxylase. We attributed this to an increased turnover rate. However,
      even with the reduced affinity propeptide, when sufficient overproduction of
      factor X is achieved, there is still a significant fraction of uncarboxylated
      recombinant factor X. We report here that the factor X of such a cell line was
      only 52% carboxylated but that the fraction of carboxylated factor X could be
      increased to 92% by coexpressing the recently identified gene for vitamin K
      epoxide reductase. Because vitamin K is in excess in both the untransfected and
      vitamin K epoxide reductase (VKOR)-transfected cells, the simplest explanation
      for this result is that VKOR catalyzes both the reduction of vitamin K epoxide to
      vitamin K and the conversion of vitamin K to vitamin K hydroquinone. In addition
      to its mechanistic relevance, this observation has practical implications for
      overproducing recombinant vitamin K-dependent proteins for therapeutic use.

PMID- 16081696
TI  - Presence of the iron exporter ferroportin at the plasma membrane of macrophages
      is enhanced by iron loading and down-regulated by hepcidin.
AB  - Ferroportin, the only mammalian iron exporter identified to date, is highly
      expressed in duodenal enterocytes and in macrophages. Several lines of evidence
      indicate that in enterocytes the iron export mediated by ferroportin occurs and
      is regulated at the basolateral cell surface, where the transporter is strongly
      expressed. By contrast, in macrophages, ferroportin has been shown in
      intracellular vesicles. We used a high-affinity antibody to specify the
      localization of endogenous ferroportin expressed in primary culture of bone
      marrow-derived macrophages, in both basal and induced conditions. Our
      observations indicate that ferroportin is expressed in vesicular compartments
      that can reach the plasma membrane of macrophages. Of importance, when
      ferroportin expression was up-regulated through iron treatment or
      erythrophagocytosis, ferroportin expression was strongly enhanced at the plasma
      membrane of macrophages. Moreover, hepcidin dramatically reduced macrophage
      ferroportin protein levels. At the subcellular level, hepcidin was shown to
      induce rapid internalization and degradation of the macrophage iron exporter.
      These data are consistent with a direct iron export by ferroportin through the
      plasma membrane of macrophages and strongly support an efficient
      posttranscriptional down-regulation of ferroportin by hepcidin in these cells.

PMID- 16081697
TI  - Ultrafast dynamics of solute-solvent complexation observed at thermal equilibrium
      in real time.
AB  - In general, the formation and dissociation of solute-solvent complexes have been
      too rapid to measure without disturbing the thermal equilibrium. We were able to
      do so with the use of two-dimensional infrared vibrational echo spectroscopy, an
      ultrafast vibrational analog of two-dimensional nuclear magnetic resonance
      spectroscopy. The equilibrium dynamics of phenol complexation to benzene in a
      benzene-carbon tetrachloride solvent mixture were measured in real time by the
      appearance of off-diagonal peaks in the two-dimensional vibrational echo spectrum
      of the phenol hydroxyl stretch. The dissociation time constant tau(d) for the
      phenol-benzene complex was 8 picoseconds. Adding two electron-donating methyl
      groups to the benzene nearly tripled the value of tau(d) and stabilized the
      complex, whereas bromobenzene, with an electron-withdrawing bromo group, formed a
      slightly weaker complex with a slightly lower tau(d). The spectroscopic method
      holds promise for studying a wide variety of other fast chemical exchange
      processes.

PMID- 16081698
TI  - Inhibition of translational initiation by Let-7 MicroRNA in human cells.
AB  - MicroRNAs (miRNAs) are approximately 21-nucleotide-long RNA molecules regulating
      gene expression in multicellular eukaryotes. In metazoa, miRNAs act by
      imperfectly base-pairing with the 3' untranslated region of target messenger RNAs
      (mRNAs) and repressing protein accumulation by an unknown mechanism. We
      demonstrate that endogenous let-7 microribonucleoproteins (miRNPs) or the
      tethering of Argonaute (Ago) proteins to reporter mRNAs in human cells inhibit
      translation initiation. M(7)G-cap-independent translation is not subject to
      repression, suggesting that miRNPs interfere with recognition of the cap.
      Repressed mRNAs, Ago proteins, and miRNAs were all found to accumulate in
      processing bodies. We propose that localization of mRNAs to these structures is a
      consequence of translational repression.

PMID- 16081699
TI  - Accurate multiplex polony sequencing of an evolved bacterial genome.
AB  - We describe a DNA sequencing technology in which a commonly available,
      inexpensive epifluorescence microscope is converted to rapid nonelectrophoretic
      DNA sequencing automation. We apply this technology to resequence an evolved
      strain of Escherichia coli at less than one error per million consensus bases. A
      cell-free, mate-paired library provided single DNA molecules that were amplified
      in parallel to 1-micrometer beads by emulsion polymerase chain reaction. Millions
      of beads were immobilized in a polyacrylamide gel and subjected to automated
      cycles of sequencing by ligation and four-color imaging. Cost per base was
      roughly one-ninth as much as that of conventional sequencing. Our protocols were
      implemented with off-the-shelf instrumentation and reagents.

PMID- 16081700
TI  - NIH funding reform.

PMID- 16081701
TI  - Stem cell politics. Frist's support raises odds for passage of stem cell bill.

PMID- 16081702
TI  - Planetary science. Cassini catches mysterious hot spot on icy-cold Enceladus.

PMID- 16081703
TI  - Planetary science. Newfound 'tenth planet' puts Pluto behind the eight ball.

PMID- 16081704
TI  - AIDS research. Male circumcision thwarts HIV infection.

PMID- 16081705
TI  - Paleoanthropology. U.S. government shifts stance on claims to ancient remains.

PMID- 16081706
TI  - Biochemistry. Cut-rate genomes on the horizon?

PMID- 16081707
TI  - Cloning. The perfect pedigree.

PMID- 16081708
TI  - Energy policy. U.S. energy bill promises some boosts for research.

PMID- 16081709
TI  - Neuroscience. Preventing Alzheimer's: a lifelong commitment?

PMID- 16081710
TI  - Protein structure. A new portrait puts potassium pore in a fresh light.

PMID- 16081712
TI  - Rencontre Assyriologique Internationale meeting. Ur's Xena: a warrior princess
      for Sumeria?

PMID- 16081711
TI  - Rencontre Assyriologique INTERNATIONALE meeting. Alas, Babylon: tracing the last
      king's desert exile.

PMID- 16081713
TI  - Rencontre Assyriologique Internationale meeting. Looted tablets pose scholar's
      dilemma.

PMID- 16081714
TI  - Epidemiology. Drugs, quarantine might stop a pandemic before it starts.

PMID- 16081715
TI  - Epidemiology. A drug makes it big-but can it deliver?

PMID- 16081716
TI  - Scrapie in ancient China?

PMID- 16081717
TI  - Co-funding in Canada: another view.

PMID- 16081718
TI  - Update on the closure of a Chilean institute.

PMID- 16081719
TI  - Canadian database in Singapore.

PMID- 16081720
TI  - Random copying and cultural evolution.

PMID- 16081721
TI  - An unexpected cover image.

PMID- 16081722
TI  - Global Voices of Science. Of stones and health: medical geology in Sri Lanka.

PMID- 16081723
TI  - Suppressing cancer: the importance of being senescent.

PMID- 16081724
TI  - Applied physics. Droplet control for microfluidics.

PMID- 16081725
TI  - Planetary science. The enigma of the martian soil.

PMID- 16081726
TI  - Developmental biology. Rac1 up for epidermal stem cells.

PMID- 16081727
TI  - The coming paradigm shift in forensic identification science.
AB  - Converging legal and scientific forces are pushing the traditional forensic
      identification sciences toward fundamental change. The assumption of discernible
      uniqueness that resides at the core of these fields is weakened by evidence of
      errors in proficiency testing and in actual cases. Changes in the law pertaining
      to the admissibility of expert evidence in court, together with the emergence of
      DNA typing as a model for a scientifically defensible approach to questions of
      shared identity, are driving the older forensic sciences toward a new scientific
      paradigm.

PMID- 16081728
TI  - Extreme waves under Hurricane Ivan.
AB  - Hurricane Ivan, a category 4 storm, passed directly over six wave-tide gauges
      deployed by the Naval Research Laboratory on the outer continental shelf in the
      northeastern Gulf of Mexico. Waves were observed with significant wave heights
      reaching 17.9 meters and maximum crest-to-trough individual wave heights of 27.7
      meters (91 feet). Analysis suggests that significant wave heights likely
      surpassed 21 meters (69 feet) and that maximum crest-to-trough individual wave
      heights exceeded 40 meters (132 feet) near the eyewall.

PMID- 16081729
TI  - Triangular and Fibonacci number patterns driven by stress on core/shell
      microstructures.
AB  - Fibonacci number patterns and triangular patterns with intrinsic defects occur
      frequently on nonplanar surfaces in nature, particularly in plants. By
      controlling the geometry and the stress upon cooling, these patterns can be
      reproduced on the surface of microstructures about 10 micrometers in diameter.
      Spherules of the Ag core/SiOx shell structure, possessing markedly uniform size
      and shape, self-assembled into the Fibonacci number patterns (5 by 8 and 13 by
      21) or the triangular pattern, depending on the geometry of the primary
      supporting surface. Under proper geometrical constraints, the patterns developed
      through self-assembly in order to minimize the total strain energy. This
      demonstrates that highly ordered microstructures can be prepared simultaneously
      across large areas by stress engineering.

PMID- 16081730
TI  - A crossover in the mechanical response of nanocrystalline ceramics.
AB  - Multimillion-atom molecular dynamics simulation of indentation of nanocrystalline
      silicon carbide reveals unusual deformation mechanisms in brittle nanophase
      materials, resulting from the coexistence of brittle grains and soft amorphous
      grain boundary phases. Simulations predict a crossover from intergranular
      continuous deformation to intragrain discrete deformation at a critical
      indentation depth. The crossover arises from the interplay between cooperative
      grain sliding, grain rotations, and intergranular dislocation formation similar
      to stick-slip behavior. The crossover is also manifested in switching from
      deformation dominated by indentation-induced crystallization to deformation
      dominated by disordering, leading to amorphization. This interplay between
      deformation mechanisms is critical for the design of ceramics with superior
      mechanical properties.

PMID- 16081731
TI  - Characterization of excess electrons in water-cluster anions by quantum
      simulations.
AB  - Water-cluster anions can serve as a bridge to understand the transition from
      gaseous species to the bulk hydrated electron. However, debate continues
      regarding how the excess electron is bound in (H2O)-n, as an interior, bulklike,
      or surface electronic state. To address the uncertainty, the properties of (H2O)
      n clusters with 20 to 200 water molecules have been evaluated by mixed quantum
      classical simulations. The theory reproduces every observed energetic, spectral,
      and structural trend with cluster size that is seen in experimental photoelectron
      and optical absorption spectra. More important, surface states and interior
      states each manifest a characteristic signature in the simulation data. The
      results strongly support assignment of surface-bound electronic states to the
      water-cluster anions in published experimental studies thus far.

PMID- 16081732
TI  - Probing the ultrafast charge translocation of photoexcited retinal in
      bacteriorhodopsin.
AB  - The ultrafast evolution of the electric field within bacteriorhodopsin was
      measured by monitoring the absorption changes of a tryptophan residue after
      excitation of retinal. The Trp absorption decreases within the first 200
      femtoseconds and then recovers on time scales typical for retinal isomerization
      and vibrational relaxation. A model of excitonic coupling between retinal and
      tryptophans shows that the signal reflects a gradual rise of the retinal
      difference dipole moment, which precedes and probably drives isomerization. The
      results suggest an intimate connection between the progressive dipole moment
      change and the retinal skeletal changes reported over the same time scale.

PMID- 16081733
TI  - An experimental approach to the percolation of sticky nanotubes.
AB  - Percolation is a statistical concept that describes the formation of an infinite
      cluster of connected particles or pathways. Lowering the percolation threshold is
      a critical issue to achieve light and low-cost conductive composites made of an
      insulating matrix loaded with conductive particles. This has interest for
      applications where charge dissipation and electrical conductivity are sought in
      films, coatings, paints, or composite materials. One route to decreasing the
      loading required for percolation is to use rod-like particles. Theoretical
      predictions indicate that this may also be achieved by altering the interaction
      potential between the particles. Although percolation may not always respond
      monotonically to interactions, the use of adhesive rods can be expected to be an
      ideal combination. By using a system made of carbon nanotubes in an aqueous
      surfactant solution, we find that very small attraction can markedly lower the
      percolation threshold. The strength of this effect can thereby have direct
      technological interest and explain the large variability of experimental results
      in the literature dealing with the electrical behavior of composites loaded with
      conducting rods.

PMID- 16081734
TI  - The pyrite-type high-pressure form of silica.
AB  - Silica (SiO2) exhibits extensive polymorphism at elevated pressures. X-ray
      diffraction measurements showed that a high-pressure form with a pyrite-type
      structure, denser than other known silica phases, is stable above 268 giga
      pascals and 1800 kelvin. The silicon coordination number increases from 6 in the
      alpha-PbO2-type phase to 6+2 in the pyrite-type phase, leading to a large
      increase in density by about 5% at the phase transition.

PMID- 16081735
TI  - Stem cell depletion through epidermal deletion of Rac1.
AB  - Mammalian epidermis is maintained by self-renewal of stem cells, but the
      underlying mechanisms are unknown. Deletion of Rac1, a Rho guanosine
      triphosphatase, in adult mouse epidermis stimulated stem cells to divide and
      undergo terminal differentiation, leading to failure to maintain the
      interfollicular epidermis, hair follicles, and sebaceous glands. Rac1 exerts its
      effects in the epidermis by negatively regulating c-Myc through p21-activated
      kinase 2 (PAK2) phosphorylation. We conclude that a pleiotropic regulator of cell
      adhesion and the cytoskeleton plays a critical role in controlling exit from the
      stem cell niche and propose that Rac and Myc represent a global stem cell
      regulatory axis.

PMID- 16081736
TI  - Protein structures forming the shell of primitive bacterial organelles.
AB  - Bacterial microcompartments are primitive organelles composed entirely of protein
      subunits. Genomic sequence databases reveal the widespread occurrence of
      microcompartments across diverse microbes. The prototypical bacterial
      microcompartment is the carboxysome, a protein shell for sequestering carbon
      fixation reactions. We report three-dimensional crystal structures of multiple
      carboxysome shell proteins, revealing a hexameric unit as the basic
      microcompartment building block and showing how these hexamers assemble to form
      flat facets of the polyhedral shell. The structures suggest how molecular
      transport across the shell may be controlled and how structural variations might
      govern the assembly and architecture of these subcellular compartments.

PMID- 16081737
TI  - Rewiring of the yeast transcriptional network through the evolution of motif
      usage.
AB  - Recent experiments revealed large-scale differences in the transcription programs
      of related species, yet little is known about the genetic basis underlying the
      evolution of gene expression and its contribution to phenotypic diversity. Here
      we describe a large-scale modulation of the yeast transcription program that is
      connected to the emergence of the capacity for rapid anaerobic growth. Genes
      coding for mitochondrial and cytoplasmic ribosomal proteins display a strongly
      correlated expression pattern in Candida albicans, but this correlation is lost
      in the fermentative yeast Saccharomyces cerevisiae. We provide evidence that this
      change in gene expression is connected to the loss of a specific cis-regulatory
      element from dozens of genes following the apparent whole-genome duplication
      event. Our results shed new light on the genetic mechanisms underlying the large
      scale evolution of transcriptional networks.

PMID- 16081738
TI  - Export-mediated assembly of mycobacterial glycoproteins parallels eukaryotic
      pathways.
AB  - Protein O-mannosylation is an essential and evolutionarily conserved post
      translational modification among eukaryotes. This form of protein modification is
      also described in Mycobacterium tuberculosis; however, the mechanism of
      mannoprotein assembly remains unclear. Evaluation of differentially translocated
      chimeric proteins and mass spectrometry to monitor glycosylation demonstrated
      that specific translocation processes were required for protein O-mannosylation
      in M. tuberculosis. Additionally, Rv1002c, a M. tuberculosis membrane protein
      homolog of eukaryotic protein mannosyltransferases, was shown to catalyze the
      initial step of protein mannosylation. Thus, the process of protein mannosylation
      is conserved between M. tuberculosis and eukaryotic organisms.

PMID- 16081739
TI  - Regulation of blood glucose by hypothalamic pyruvate metabolism.
AB  - The brain keenly depends on glucose for energy, and mammalians have redundant
      systems to control glucose production. An increase in circulating glucose
      inhibits glucose production in the liver, but this negative feedback is impaired
      in type 2 diabetes. Here we report that a primary increase in hypothalamic
      glucose levels lowers blood glucose through inhibition of glucose production in
      rats. The effect of glucose requires its conversion to lactate followed by
      stimulation of pyruvate metabolism, which leads to activation of adenosine
      triphosphate (ATP)-sensitive potassium channels. Thus, interventions designed to
      enhance the hypothalamic sensing of glucose may improve glucose homeostasis in
      diabetes.

PMID- 16081740
TI  - Hemodynamic signals correlate tightly with synchronized gamma oscillations.
AB  - Functional imaging methods monitor neural activity by measuring hemodynamic
      signals. These are more closely related to local field potentials (LFPs) than to
      action potentials. We simultaneously recorded electrical and hemodynamic
      responses in the cat visual cortex. Increasing stimulus strength enhanced spiking
      activity, high-frequency LFP oscillations, and hemodynamic responses. With
      constant stimulus intensity, the hemodynamic response fluctuated; these
      fluctuations were only loosely related to action potential frequency but tightly
      correlated to the power of LFP oscillations in the gamma range. These
      oscillations increase with the synchrony of synaptic events, which suggests a
      close correlation between hemodynamic responses and neuronal synchronization.

PMID- 16081741
TI  - Coupling between neuronal firing, field potentials, and FMRI in human auditory
      cortex.
AB  - Functional magnetic resonance imaging (fMRI) is an important tool for
      investigating human brain function, but the relationship between the
      hemodynamically based fMRI signals in the human brain and the underlying neuronal
      activity is unclear. We recorded single unit activity and local field potentials
      in auditory cortex of two neurosurgical patients and compared them with the fMRI
      signals of 11 healthy subjects during presentation of an identical movie segment.
      The predicted fMRI signals derived from single units and the measured fMRI
      signals from auditory cortex showed a highly significant correlation (r = 0.75, P
      < 10(-47)). Thus, fMRI signals can provide a reliable measure of the firing rate
      of human cortical neurons.

PMID- 16081742
TI  - Do scientific publications change anything?

PMID- 16081744
TI  - Gaps in injury statistics: multiple injury profiles reveal them and provide a
      comprehensive account.
AB  - OBJECTIVE: To demonstrate the benefit of using multiple injury profiles (MIP) as
      an alternative to "primary diagnosis," for the presentation and analysis of
      multiple injuries in populations. METHODS: Retrospective analysis of national
      trauma registry data in Israel between 1 January 1998 and 31 December 2002.
      Multiple diagnoses per patient were recorded. A primary diagnosis was selected
      for each patient and data were presented twice: first by selecting a primary
      diagnosis and then using multiple injury profiles. RESULTS: 23 909 transport
      casualties were included. Findings show that MIP enable the identification of all
      patients with a specific injury, even where secondary. The proportion of
      additional injuries recorded when using MIP ranged from 12% in head injuries to
      270% for facial injuries. Based on the primary diagnosis patients with head,
      chest, and abdominal injuries had a 5-6% inpatient death rate each. Multiple
      injury profiles of the same population reveal that an isolated head injury has a
      3% inpatient death rate, isolated chest and isolated abdomen have a 1% inpatient
      death rate, while combined head and chest casualties have a 21% inpatient death
      rate. CONCLUSIONS: Multiple injury profiles are a new approach that enables
      presenting an improved picture of injury in a population.

PMID- 16081745
TI  - Do wrist guards have the potential to protect against wrist injuries in
      bicycling, micro scooter riding, and monkey bar play?
AB  - OBJECTIVE: To test the potential of wrist guards to prevent wrist injury in
      recreational activities that require good grip strength and hand dexterity.
      METHODS: Forty eight children aged 5-8 years from one Melbourne school
      volunteered for tests chosen or devised following a review of the literature on
      the effects of orthoses use and hand function. RESULTS: Wrist guard wearing
      significantly degraded grip strength, bicycle steering, and performance on a
      monkey bar. Micro scooter steering was not significantly affected by their use.
      CONCLUSION: Wrist guards designed for skating are not recommended for bicycle
      riding and playing on climbing apparatus, and their suitability for scooter
      riding requires further investigation.

PMID- 16081746
TI  - Differentials in poisoning rates of young Australian children according to
      residential location and geographical remoteness.
AB  - OBJECTIVES: To assess differentials in the poisoning rates of children aged 0-4
      years according to residential location and geographical remoteness. DESIGN:
      Cross sectional study based on hospitalizations. SETTING: Australia. SUBJECTS:
      Children aged 0-4 years admitted to hospital due to poisoning during the
      financial year 1996-97. MAIN OUTCOME MEASURES: Crude rates of hospitalization.
      RESULTS: The rate of hospitalization due to poisoning peaked in the third year
      and second year of life for medicinal and non-medicinal substances respectively.
      Rates were significantly higher among children aged 0-4 years residing in rural
      and remote areas when compared with those residing in metropolitan areas, and
      rate differentials increased with geographical remoteness. CONCLUSIONS: The
      observed differentials suggest the need for targeted research and prevention
      efforts aimed at rural and remote area communities. A detailed empirical study is
      recommended, involving the assessment of risk factors and an in-home hazard
      checklist, as a precursor to any intervention program.

PMID- 16081747
TI  - The emergency department approach to violently injured patient care: a regional
      survey.
AB  - OBJECTIVE: Since the early 1990s public health workers have challenged healthcare
      practitioners to take an active role in violence prevention with patients aged 10
      24 years. Emergency department (ED) clinicians are uniquely positioned to
      identify, assess, and refer youth involved in violent events. The objective of
      this study was to describe ED directors' estimate of the number of violently
      injured youth seen, the presence of established protocols or guidelines for
      handling youth violence, and the type of training programs offered to ED
      physicians regarding this issue. METHODS: The authors conducted a survey of EDs
      (n = 64) in the Philadelphia metropolitan region to determine the standard of ED
      care for violently injured youths. Half of the EDs were in urban areas and half
      in suburban. RESULTS: A total of 41 out of 64 (64.1%) ED directors completed and
      returned the written questionnaire. In addition to treating the specific injuries
      sustained, ED responses to youth violence primarily involved talking with
      patients about the events surrounding the injury. The estimated number of
      violently injured youth seen per month varied considerably. Twenty four directors
      (58.5%) estimated that their institution treated fewer than 10 per month; 10
      (24.4%) reported 11-30, and seven (17.1%) mostly large urban hospitals, saw more
      than 30 per month. Although most hospitals reported that the staff counsels
      patients about safety concerns, only 17% offered their staff formal training
      programs on youth violence. CONCLUSIONS: To address the prevention of youth
      violence, EDs need specific training programs for ED staff, as well as systematic
      risk assessment and referral resources for structured intervention and follow up.

PMID- 16081748
TI  - Validation of parent self reported home safety practices.
AB  - OBJECTIVES: To evaluate the validity of parents' self reported home safety
      practices concerning smoke detectors, bike helmets, car seats, and water heater
      temperature. SETTING: Parents of children 12 years old and under whose child had
      made at least one visit to a study clinic in the years 2000-2003. METHODS: As
      part of a randomized controlled trial to improve patient provider communication
      and preventive practices, parents' responses to telephone interview were compared
      with observations of safety practices during a home visit. Home visits were
      completed within nine weeks of the telephone interview. Parents were not told
      that the visit was part of a validation study and home visit observers were
      unaware of the interview responses. The authors calculated sensitivities,
      specificities, positive and negative predictive values, and their corresponding
      confidence intervals. RESULTS: Sensitivity (0.78 to 0.98) and positive predictive
      values (0.75 to 1.00) were high for all items. Specificities and negative
      predictive values were more variable and the highest estimates (specificity 0.95
      to 1.00, negative predictive value 0.95 to 0.97) were for car seat types.
      CONCLUSIONS: The results suggest that parent self report practice of certain
      injury prevention behaviors (owning a car seat, hot water temperatures) is
      reliable, whereas self reports on other practices (working smoke detectors,
      properly fitting bike helmets) may be overstated.

PMID- 16081749
TI  - Cross national study of injury and social determinants in adolescents.
AB  - OBJECTIVES: To compare estimates of the prevalence of injury among adolescents in
      35 countries, and to examine the consistency of associations cross nationally
      between socioeconomic status then drunkenness and the occurrence of adolescent
      injury. DESIGN: Cross sectional surveys were obtained from national samples of
      students in 35 countries. Eight countries asked supplemental questions about
      injury. SETTING: Surveys administered in classrooms. SUBJECTS: Consenting
      students (n = 146 440; average ages 11-15 years) in sampled classrooms. 37 878
      students (eight countries) provided supplemental injury data.Exposure measures:
      Socioeconomic status (material wealth, poverty) and social risk taking
      (drunkenness). OUTCOME MEASURES: Specific types and locations of medically
      treated injury. RESULTS: By country, reports of medically treated injuries ranged
      from 33% (1060/3173) to 64% (1811/2833) of boys and 23% (740/3172) to 51%
      (1485/2929) of girls, annually. Sports and recreation were the most common
      activities associated with injury. High material wealth was positively (OR>1.0;
      p<0.05) and consistently (6/8 countries) associated with medically treated and
      sports related injuries. Poverty was positively associated with fighting injuries
      (6/8 countries). Drunkenness (social risk taking) was positively (p<0.01) and
      consistently (8/8 countries) associated with medically treated, street, and
      fighting injuries, but not school and sports related injuries. CONCLUSION: The
      high prevalence of adolescent injury confirms its importance as a health problem.
      Social gradients in risk for adolescent injury were illustrated cross nationally
      for some but not all types of adolescent injury. These gradients were most
      evident when the etiologies of specific types of adolescent injury were examined.
      Prevention initiatives should focus upon the etiologies of specific injury types,
      as well as risk oriented social contexts.

PMID- 16081750
TI  - Trip characteristics of vehicle crashes involving child passengers.
AB  - OBJECTIVES: To describe the trip characteristics of vehicle crashes involving
      children, and to examine the effect of situational factors on front row seating
      or inappropriate restraint for young children. METHODS: A cross sectional study
      was conducted on children <16 years in crashes of insured vehicles in 15 US
      states, with data collected using insurance claims records and a telephone
      interview. A descriptive analysis of the characteristics of vehicle crashes
      involving children was performed. Multivariate Poisson regression was used to
      identify situational factors associated with inappropriate restraint or front row
      seating. RESULTS: These data suggest that children were traveling in vehicles
      involved in crashes that occurred under usual driving circumstances-that is,
      closer to home (60%), on a local road (56%), during normal daytime hours (71%),
      within areas with relatively lower posted speed limits (76%). Compared with
      children involved in morning crashes, those in daytime crashes (RR = 1.65, 95% CI
      1.13 to 2.49) or in night-time crashes (RR = 1.63, 95% CI 1.09 to 2.67) were more
      likely to be sitting in the front seat. Children involved in night-time crashes
      were more likely to be inappropriately restrained (RR = 1.12, 95% CI 1.01 to
      1.22) than those in daytime crashes. Children riding with two or more additional
      passengers were more likely to be inappropriately restrained (RR = 1.12, 95% CI
      1.02 to 1.27) than those with no other passengers. CONCLUSIONS: Educational
      initiatives should aim to increase the perception that parents have about the
      potential crash risk of everyday trips. Some situational characteristics of trips
      were associated with inappropriate restraint and front row seating behaviors for
      young children.

PMID- 16081751
TI  - Cochrane Library feedback.

PMID- 16081752
TI  - Driver dependent factors and the risk of causing a collision for two wheeled
      motor vehicles.
AB  - OBJECTIVE: To assess the effect of driver dependent factors on the risk of
      causing a collision for two wheeled motor vehicles (TWMVs). DESIGN: Case control
      study. SETTING: Spain, from 1993 to 2002. SUBJECTS: All drivers of TWMVs involved
      in the 181 551 collisions between two vehicles recorded in the Spanish registry
      which did not involve pedestrians, and in which at least one of the vehicles was
      a TWMV and only one driver had committed a driving infraction. The infractor and
      non-infractor drivers constituted the case and control groups, respectively. MAIN
      OUTCOME MEASURES: Logistic regression analyses were used to obtain crude and
      adjusted odds ratio estimates for each of the driver related factors recorded in
      the registry (age, sex, nationality, psychophysical factors, and speeding
      infractions, among others). RESULTS: Inappropriate speed was the variable with
      the greatest influence on the risk of causing a collision, followed by excessive
      speed and driving under the influence of alcohol. Younger and older drivers,
      foreign drivers, and driving without a valid license were also associated with a
      higher risk of causing a collision. In contrast, helmet use, female sex, and
      longer time in possession of a driving license were associated with a lower risk.
      CONCLUSIONS: Although the main driver dependent factors related to the risk of
      causing a collision for a TWMV were similar to those documented for four wheeled
      vehicles, several differences in the pattern of associations support the need to
      study moped and motorcycle crashes separately from crashes involving other types
      of vehicles.

PMID- 16081753
TI  - United States pedestrian fatality rates by vehicle type.
AB  - OBJECTIVE: To describe the relation between motor vehicle type and the risk of
      fatally injuring a pedestrian. DESIGN: The risk of killing a pedestrian was
      measured as the number of pedestrian fatalities per billion miles of vehicle
      travel by each vehicle type in the US in 2002 as reported by the National Highway
      Traffic Safety Administration's Fatality Analysis Reporting System.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Rates for each vehicle type by sex,
      age, and rural/urban roadway type and rate comparisons using relative risks (RR)
      and 95% confidence intervals (CIs). RESULTS: Passenger cars and light trucks
      (vans, pickups, and sport utility vehicles) accounted for 46.1% and 39.1%,
      respectively, of the 4875 deaths, with the remainder split among motorcycles,
      buses, and heavy trucks. Compared with cars, the RR of killing a pedestrian per
      vehicle mile was 7.97 (95% CI 6.33 to 10.04) for buses; 1.93 (95% CI 1.30 to
      2.86) for motorcycles; 1.45 (95% CI 1.37 to 1.55) for light trucks, and 0.96 (95%
      CI 0.79 to 1.18) for heavy trucks. Compared with cars, buses were 11.85 times
      (95% CI 6.07 to 23.12) and motorcycles were 3.77 times (95% CI 1.40 to 10.20)
      more likely per mile to kill children 0-14 years old. Buses were 16.70 times (95%
      CI 7.30 to 38.19) more likely to kill adults age 85 or older than were cars. The
      risk of killing a pedestrian per vehicle mile traveled in an urban area was 1.57
      times (95% CI 1.47 to 1.67) the risk in a rural area. CONCLUSIONS: Outcomes
      reflect the ways in which a vehicle's characteristics (mass, front end design,
      and visibility) and its degree of interaction with pedestrians affect its risk
      per mile. Modifications in vehicle design might reduce pedestrian injury. The
      greatest impact on overall US pedestrian mortality will result from reducing the
      risk from the light truck category.

PMID- 16081754
TI  - Unintentional injury depictions in popular children's television programs.
AB  - OBJECTIVES: The frequency and magnitude of depictions of risky events and
      unintentional injuries in top ranked children's animated and live action
      television programs was assessed. METHODS: Qualitative and quantitative media
      content analysis were used. Scenes from television episodes were examined for the
      depiction of risky events and unintentional injuries. RESULTS: A total of 201
      actual and potential injury related events were tabulated in 99 episodes aired in
      2003 and 2004. Only 26% of the risky events depicted led to an injury or physical
      consequence. More than 80% of the events involved behavioral or environmental
      risk factors. Safety factors were not present in over 90% of risky events
      depicted. The general tone and context of events was humor or indifference rather
      than concern or action, with little or no relevance to the plot. CONCLUSION:
      Unintentional injuries are the leading cause of death and disability for
      children, yet animated and live action television programs marketed to children
      continue to portray injury risk inaccurately. Working with the children's
      television production industry to improve injury depiction is a much needed
      advocacy activity.

PMID- 16081755
TI  - Should football players wear custom fitted mouthguards? Results from a group
      randomised controlled trial.
AB  - OBJECTIVE: Head/orofacial (H/O) injuries are common in Australian rules football.
      Mouthguards are widely promoted to prevent these injuries, in spite of the lack
      of formal evidence for their effectiveness. DESIGN: The Australian football
      injury prevention project was a cluster randomized controlled trial to evaluate
      the effectiveness of mouthguards for preventing H/O injuries in these players.
      SETTING AND SUBJECTS: Twenty three teams (301 players) were recruited from the
      largest community football league in Australia. INTERVENTION: Teams were randomly
      allocated to either the MG: custom made mouthguard or C: control (usual
      mouthguard behaviours) study arm. MAIN OUTCOME MEASURES: All injuries,
      participation in training and games, and mouthguard use were monitored over the
      2001 playing season. Injury rates were calculated as the number of injuries per
      1000 person hours of playing time. Adjusted incidence rate ratios were obtained
      from Poisson regression models. RESULTS: Players in both study arms wore
      mouthguards, though it is unlikely that many controls wore custom made ones.
      Wearing rates were higher during games than training. The overall rate of H/O
      injury was 2.7 injuries per 1000 exposure hours. The rate of H/O injury was
      higher during games than training. The adjusted H/O injury incidence rate ratio
      was 0.56 (95% CI 0.32 to 0.97) for MG versus C during games and training,
      combined. CONCLUSIONS: There was a significant protective effect of custom made
      mouthguards, relative to usual mouthguard use, during games. However, the control
      players still wore mouthguards throughout the majority of games and this could
      have diluted the effect.

PMID- 16081756
TI  - People and guns involved in denied and completed handgun sales.
AB  - OBJECTIVE: Denial of handgun purchases by prohibited people and knowledge of the
      structure of gun commerce have helped to deter and prevent firearm violence. The
      authors hypothesize that handguns involved in a denied purchase would more
      closely resemble those used in crime compared with handguns sold. DESIGN: Cross
      sectional. SETTING: Denied and completed handgun sales in California, 1998-2000.
      MAIN OUTCOME MEASURES: Handgun and purchaser characteristics of denied and
      completed sales were compared. In particular, handgun characteristics most
      closely associated with crime guns (type, caliber, barrel length, price) were
      examined. RESULTS: Compared with handguns sold, handguns in denied sales were
      somewhat more likely to be semiautomatic pistols (74.6% v 69.4%), to have short
      barrels (25.9% v 22.2%), and be of medium caliber (48.9% v 37.3%). Ten percent of
      the handguns in denied sales and 3.4% of handguns sold were identified as
      inexpensive. CONCLUSIONS: The characteristics of denied handguns are similar to
      those seen among crime guns. Both groups of guns may reflect the desirability for
      criminal purposes of pistols, which have larger ammunition capacities than other
      handguns, and short barrels, which increase their ability to be concealed.

PMID- 16081757
TI  - Recurrent early childhood injuries among disadvantaged children in primary care
      settings.
AB  - OBJECTIVE: To examine differences in social risk factors and health care use
      between young children with and without recurrent injuries. DESIGN: Retrospective
      cohort study using administrative claims and medical records. Children with no,
      one, or more than one injury were compared. SETTING: Integrated public healthcare
      system. SUBJECTS: All children born at Denver Health Medical Center (DHMC) in
      1993 who continued care there beyond 15 months of age. Children were followed to
      36 months. OUTCOME MEASURES: Sociodemographic information, service use, injury
      episodes, cause of injury, and social risk factors. RESULTS: 371 injury episodes
      occurred among 817 children. In the study cohort, 7% had >1 injury episode, 26%
      had one injury, and 67% had none. Among children with >1 injury episode, 78% had
      at least one social risk factor compared with 63% of children with one injury and
      52% of children with none (p<0.0001). Risk factors for >1 injury included
      maternal substance abuse (p = 0.0003), maternal age under 18 years (p = 0.04), a
      primary caregiver who was single (p<0.0001) or mentally ill (p = 0.03), and a
      history of family violence (p = 0.01). Multiple injury episodes were associated
      with increased non-injury service use, including primary care visits (p<0.0001),
      emergency department visits (p<0.0001), and total non-injury encounters
      (p<0.0001). CONCLUSIONS: Children with recurrent injury were more likely to have
      social risk factors, and used DHMC more frequently, than children with one or no
      injuries. Children with risk factors for recurrent injury can be identified and
      injury prevention counseling can be delivered to their families at their multiple
      visits to the system.

PMID- 16081758
TI  - Anti-glycosyl antibodies in lipid rafts of the enterocyte brush border: a
      possible host defense against pathogens.
AB  - The pig small intestinal brush border is a glycoprotein- and glycolipid-rich
      membrane that functions as a digestive/absorptive surface for dietary nutrients
      as well as a permeability barrier for pathogens. The present work was performed
      to identify carbohydrate-binding (lectinlike) proteins associated with the brush
      border. Chromatography on lactose-agarose was used to isolate such proteins, and
      their localization was studied biochemically and by immunofluorescence microscopy
      and immunogold electron microscopy. IgG and IgM were the two major proteins
      isolated, indicating that naturally occurring anti-glycosyl antibodies are among
      the major lectinlike proteins in the gut. IgG and IgM as well as IgA were
      localized to the enterocyte brush border, and a brief lactose wash partially
      released all three immunoglobulins from the membrane, indicating that anti
      glycosyl antibodies constitute a major part of the immunoglobulins at the lumenal
      surface of the gut. The antibodies were associated with lipid rafts at the brush
      border, and they frequently (52%) coclustered with the raft marker galectin 4. A
      lactose wash increased the susceptibility of the brush border toward lectin
      peanut agglutin and cholera toxin B, suggesting that anti-glycosyl antibodies
      compete with other carbohydrate-binding proteins at the lumenal surface of the
      gut. Thus anti-glycosyl antibodies constitute a major group of proteins
      associated with the enterocyte brush border membrane. We propose they function by
      protecting the lipid raft microdomains of the brush border against pathogens.

PMID- 16081759
TI  - Colonic blood flow responses in experimental colitis: time course and underlying
      mechanisms.
AB  - Human inflammatory bowel diseases (IBD) are associated with significant
      alterations in intestinal blood flow, the direction and magnitude of which change
      with disease progression. The objectives of this study were to determine the time
      course of changes in colonic blood perfusion that occur during the development of
      dextran-sodium-sulfate (DSS)-induced colonic inflammation and to address the
      mechanisms that may underlie these changes in blood flow. Intravital microscopy
      was used to quantify blood flow (from measurements of vessel diameter and red
      blood cell velocity) in different-sized submucosal arterioles of control and
      inflamed colons in wild-type (WT) mice. A significant (18-30%) reduction in blood
      flow was noted in the smallest arterioles (<40 microm diameter) on days 4-6 of
      DSS colitis. The arteriolar responses to bradykinin in control and DSS-treated WT
      mice revealed an impaired endothelium-dependent, but not endothelium-independent,
      vasodilation in the inflamed colon. However, this impaired vasodilatory response
      to bradykinin after DSS treatment was not evident in mutant mice that overexpress
      Cu,Zn-superoxide dismutase. Rescue of the bradykinin-induced vasodilation during
      DSS colitis was also observed in mice that are genetically deficient in the
      NAD(P)H oxidase subunit gp91(phox). These findings indicate that the decline in
      blood flow during experimental colitis may result from a diminished capacity of
      colonic arterioles to respond to endogenous endothelium-dependent vasodilators
      like bradykinin and that NAD(P)H oxidase-derived superoxide plays a major role in
      the induction of the inflammation-induced endothelium-dependent arteriolar
      dysfunction.

PMID- 16081760
TI  - Comparative studies of duodenal and macrophage ferroportin proteins.
AB  - Intestinal epithelial cells and reticuloendothelial macrophages are,
      respectively, involved in diet iron absorption and heme iron recycling from
      senescent erythrocytes, two critical processes of iron homeostasis. These cells
      appear to use the same transporter, ferroportin (Slc40a1), to export iron. The
      aim of this study was to compare the localization, expression, and regulation of
      ferroportin in both duodenal and macrophage cells. Using a high-affinity purified
      polyclonal antibody, we analyzed the localization and expression of ferroportin
      protein in the spleen, liver, and duodenum isolated from normal mice as well as
      from well-characterized mouse models of altered iron homeostasis. Ferroportin was
      found to be predominantly expressed in enterocytes of the duodenum, in splenic
      macrophages, and in liver Kupffer cells. Interestingly, the protein species
      detected in these cells migrated differently on SDS-PAGE. These differences in
      apparent molecular masses were partly explained by posttranslational complex N
      linked glycosylations. In addition, in enterocytes, the transporter was mostly
      expressed at the basolateral membrane, whereas in bone marrow-derived
      macrophages, ferroportin was found predominantly localized in the intracellular
      vesicular compartment. However, some microdomains positive for ferroportin were
      also detected at the plasma membrane of macrophages. Despite these differences,
      we observed a parallel upregulation of ferroportin expression in tissue
      macrophages and enterocytes in response to iron-restricted erythropoiesis,
      suggesting that iron homeostasis is likely maintained through coordinate
      expression of the iron exporter in both intestinal and phagocytic cells. Our data
      also confirm a predominant regulation of ferroportin through systemic
      regulator(s) likely including hepcidin.

PMID- 16081761
TI  - Acid increases MAPK-mediated proliferation in Barrett's esophageal adenocarcinoma
      cells via intracellular acidification through a Cl-/HCO3- exchanger.
AB  - Abundant epidemiological evidence links acid reflux to adenocarcinoma in
      Barrett's esophagus, but few studies have examined the cellular mechanisms by
      which acid promotes this neoplastic progression. We hypothesized that
      extracellular acid exposure causes intracellular acidification that triggers MAPK
      signaling and proliferation in Barrett's epithelial cells. We tested that
      hypothesis in a Barrett's-derived esophageal adenocarcinoma cell line (SEG-1).
      SEG-1 cells were exposed to varying concentrations of acid, and intracellular pH
      (pH(i)) was measured by 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein
      microfluorimetry. After acid exposure, ERK and p38 MAPK activation were measured
      by Western blot analysis and an immune complex kinase assay. Proliferation was
      measured by Coulter counter cell counts and a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide incorporation assay. Exposure of SEG-1 cells to
      solutions with a pH between 3 and 6.5 caused a rapid, reversible decrease in
      pH(i) to a level approximately equal to extracellular pH. Acid exposure caused a
      rapid activation of both ERK and p38 MAPKs and also resulted in pH-dependent
      increases in cell number, with a maximum increase of 41% observed at pH 6.0. The
      MAPK activation and proliferation in SEG-1 cells induced by acid exposure could
      be blocked by pretreatment with disodium 4,4'-diisothiocyanatostilbine-2,2'
      disulfonate (DIDS), which prevents intracellular acidification by inhibiting the
      Cl(-)/HCO(3)(-) exchanger. In conclusion, in SEG-1 cells, extracellular acid
      exposure causes intracellular acidification, which activates MAPK and causes
      proliferation. The magnitude of these effects is pH dependent, and the effects
      can be inhibited by preventing intracellular acidification with DIDS.

PMID- 16081762
TI  - Decreased sucrase and lactase activity in iron deficiency is accompanied by
      reduced gene expression and upregulation of the transcriptional repressor PDX-1.
AB  - Disaccharidases are important digestive enzymes whose activities can be reduced
      by iron deficiency. We hypothesise that this is due to reduced gene expression,
      either by impairment to enterocyte differentiation or by iron-sensitive
      mechanisms that regulate mRNA levels in enterocytes. Iron-deficient Wistar rats
      were generated by dietary means. The enzyme activities and kinetics of sucrase
      and lactase were tested as well as the activity of intestinal alkaline
      phosphatase (IAP)-II because it is unrelated to carbohydrate digestion. mRNA
      levels of beta-actin, sucrase, lactase, and the associated transcription factors
      pancreatic duodenal homeobox (PDX)-1, caudal-related homeobox (CDX)-2, GATA
      binding protein (GATA)-4, and hepatocyte nuclear factor (HNF)-1 were measured by
      real-time PCR. Spatial patterns of protein and gene expression were assessed by
      immunofluorescence and in situ hybridization, respectively. It was found that
      iron-deficient rats had significantly lower sucrase (19.5% lower) and lactase
      (56.8% lower) but not IAP-II activity than control rats. Kinetic properties of
      both enzymes remained unchanged from controls, suggesting a decrease in the
      quantity of enzyme present. Sucrase and lactase mRNA levels were reduced by 44.5%
      and 67.9%, respectively, by iron deficiency, suggesting that enzyme activity is
      controlled primarily by gene expression. Iron deficiency did not affect the
      pattern of protein and gene expression along the crypt to villus axis. Expression
      of PDX-1, a repressor of sucrase and lactase promoters, was 4.5-fold higher in
      iron deficiency, whereas CDX-2, GATA-4, and HNF-1 levels were not significantly
      different. These data suggest that decreases in sucrase and lactase activities
      result from a reduction in gene expression, following from increased levels of
      the transcriptional repressor PDX-1.

PMID- 16081763
TI  - Involvement of histone acetyltransferase (HAT) in ethanol-induced acetylation of
      histone H3 in hepatocytes: potential mechanism for gene expression.
AB  - Ethanol treatment increases gene expression in the liver through mechanisms that
      are not clearly understood. Histone acetylation has been shown to induce
      transcriptional activation. We have investigated the characteristics and
      mechanisms of ethanol-induced histone H3 acetylation in rat hepatocytes.
      Immunocytochemical and immunoblot analysis revealed that ethanol treatment
      significantly increased H3 acetylation at Lys9 with negligible effects at Lys14, 
      18, and -23. Acute in vivo administration of alcohol in rats produced the same
      results as in vitro observations. Nuclear extracts from ethanol-treated
      hepatocytes increased acetylation in H3 peptide to a greater extent than extracts
      from untreated cells, suggesting that ethanol either increased the expression
      level or the specific activity of histone acetyltransferases (HAT). Use of
      different H3 peptides indicated that ethanol selectively modulated HAT(s)
      targeting H3-Lys9. Treatment with acetate, an ethanol metabolite, also increased
      acetylation of H3-Lys9 and modulated HAT(s) in the same manner as ethanol,
      suggesting that acetate mediates the ethanol-induced effect on HAT. Inhibitors of
      MEK (U0126) and JNK (SP600125), but not p38 MAPK inhibitor (SB203580), suppressed
      ethanol-induced H3 acetylation. However, U0126 and SP600125 did not significantly
      affect ethanol-induced effect on HAT, suggesting that ERK and JNK regulate
      histone acetylation through a separate pathway(s) that does not involve
      modulation of HAT. Chromatin immunoprecipitation assay demonstrated that ethanol
      treatment increased the association of the class I alcohol dehydrogenase (ADH I)
      gene with acetylated H3-Lys9. These data provide first evidence that ethanol
      increases acetylation of H3-Lys9 through modulation of HAT(s) and that histone
      acetylation may underlie the mechanism for ethanol-induced ADH I gene expression.

PMID- 16081764
TI  - Effects of the prostaglandins PGF2alpha and PGE2 on calcium signaling in rat
      hepatocyte doublets.
AB  - Coordination of intercellular Ca2+ signals is important for certain hepatic
      functions including biliary flow and glucose output. Prostaglandins, such as
      PGF2alpha and PGE2, may modify these hepatocyte functions by inducing Ca2+
      increase, but very little is known about the organization of the Ca2+ signals
      induced by these agonists. We studied Ca2+ signals induced by PGF2alpha and PGE2
      in fura-2 AM-loaded hepatocyte doublets. Even though both prostaglandins induced
      Ca2+ oscillations, neither PGF2alpha nor PGE2 induced coordinated Ca2+
      oscillations in hepatocyte doublets. Gap junction permeability (GJP), assessed by
      fluorescence recovery after photobleaching, showed that this absence of
      coordination was not related to a defect in GJP. Inositol (1,4,5)trisphosphate
      [Ins(1,4,5)P3] assays and the increase in Ins(1,4,5)P3 receptor sensitivity to
      Ins(1,4,5)P3 observed in response to thimerosal suggested that the absence of
      coordination was a consequence of the very small quantity of Ins(1,4,5)P3 formed
      by these prostaglandins. Furthermore, when PGE2 and PGF2alpha were added just
      before norepinephrine, they favored the coordination of Ca2+ signals induced by
      norepinephrine. However, GJP between hepatocyte doublets was strongly inhibited
      by prolonged (>or=2 h) treatment with PGF2alpha, thereby preventing the
      coordination of Ca2+ oscillations induced by norepinephrine in these cells. Thus,
      depending on the time window, prostaglandins, specially PGF2alpha, may enhance or
      diminish the propagation of Ca2+ signals. They may therefore contribute to the
      fine tuning of Ca2+ wave-dependent functions, such as nerve stimulation, hormonal
      regulation of liver metabolism, or bile secretion, in both normal and pathogenic
      conditions.

PMID- 16081765
TI  - Human acidic mammalian chitinase erroneously known as eosinophil chemotactic
      cytokine is not the ortholog of mouse YM1.

PMID- 16081766
TI  - APC-independent NK cell activation.

PMID- 16081767
TI  - Effect of CD3/CD28 bead-activated T cells on leukemic B cells in chronic
      lymphocytic leukemia.

PMID- 16081768
TI  - 2B4/CD48-mediated regulation of lymphocyte activation and function.
AB  - 2B4 (CD244) is a member of the CD2 subset of the Ig superfamily. This molecule is
      expressed on innate immune cells, including NK cells, and on subsets of T cells.
      The 2B4 molecule interacts with CD48, which is widely expressed on hemopoietic
      cells. Although earlier reports demonstrated a role for 2B4 as an activating
      receptor in both mice and humans, recent studies of 2B4-deficient mice have
      suggested that 2B4 functions predominantly as an inhibitory receptor in mice. In
      addition, 2B4 may also act as a costimulatory ligand for cells expressing CD48.
      Thus, the 2B4 molecule is more multifunctional than previously understood. In
      this study, we delineate the current view of 2B4-CD48 interactions among
      lymphocytes and other cells.

PMID- 16081769
TI  - Cutting edge: critical role of CXCL16/CXCR6 in NKT cell trafficking in allograft
      tolerance.
AB  - It is well-documented that certain chemokines or their receptors play important
      roles in the graft rejection. However, the roles of chemokines and their
      receptors in the maintenance of transplantation tolerance remain unclear. In this
      study, we demonstrate that blocking of the interaction between the chemokine
      receptor, CXCR6, highly expressed on V alpha14+ NKT cells and its ligand, CXCL16,
      resulted in the failure to maintain graft tolerance and thus in the induction of
      acceleration of graft rejection. In a mouse transplant tolerance model, the
      expression of CXCL16 was up-regulated in the tolerated allografts, and anti
      CXCL16 mAb inhibited intragraft accumulation of NKT cells. In vitro experiments
      further showed that blocking of CXCL16/CXCR6 interaction significantly affected
      not only chemotaxis but also cell adhesion of NKT cells. These results
      demonstrate the unique role of CXCL16 and CXCR6 molecules in the maintenance of
      cardiac allograft tolerance mediated by NKT cells.

PMID- 16081770
TI  - Cutting edge: chemoattractant receptor-homologous molecule expressed on Th2 cells
      plays a restricting role on IL-5 production and eosinophil recruitment.
AB  - PGs play key regulatory roles in inflammation and immunity. PGD2, released from
      mast cells and Th2 cells during allergic responses, has recently been shown to
      target a novel receptor, chemoattractant receptor-homologous molecule expressed
      TH2 cells (CRTH2), in addition to the classic PGD (DP) receptor. CRTH2 is
      expressed on Th2 cells and eosinophils and mediates chemotaxis of these cells to
      PGD2. Thus, CRTH2 is thought to be a key receptor mediating eosinophil and Th2
      cell recruitment during allergic responses. To examine the role of CRTH2 in this
      context in vivo, we generated CRTH2 knockout mice. Surprisingly, in an allergic
      inflammatory model of asthma, CRTH2 knockout mice showed enhanced eosinophil
      recruitment into the lung compared with wild-type littermate mice. This is
      consistent with our observation that CRTH2 knockout cells produce significantly
      higher amounts of IL-5 and IL-3 in vitro. These results suggest a nonredundant
      role of CRTH2 in restricting eosinophilia and allergic response in vivo.

PMID- 16081771
TI  - Cutting edge: polymorphisms in the ICOS promoter region are associated with
      allergic sensitization and Th2 cytokine production.
AB  - The establishment of ICOS as an important regulator of Th2 development and
      effector function makes the ICOS locus an attractive candidate for Th2-mediated
      diseases, such as asthma and allergy. In evaluation of this candidate locus in
      humans, we identified 11 variants and determined that two in the putative
      promoter region are significantly associated with allergic sensitization and
      serum IgE levels. In addition, cultures of activated PBMCs from individuals
      homozygous for the associated polymorphisms produced increased levels of the Th2
      cytokines, IL-4, IL-5, and IL-13, as well as TNF-alpha compared with controls.
      One of the polymorphisms, -1413G/A, demonstrated differential NF-kappaB binding
      in mobility shift analysis, suggesting that this polymorphism has functional
      consequences. Overall, these data demonstrate that ICOS is a susceptibility gene
      for allergic sensitization, perhaps through the promotion of Th2 differentiation.

PMID- 16081772
TI  - Cutting edge: a single MHC class Ia is sufficient for CD8 memory T cell
      differentiation.
AB  - Recent studies have suggested a role for MHC class Ib molecules in providing
      signals for memory T cell differentiation during the early phases of acute
      infection. To test this hypothesis, we assessed the development of effector and
      memory CD8 T cells in transgenic mice expressing a single chain H-2D(d)/beta2
      microglobulin (beta2M) fusion protein on a beta2M-deficient background. These
      mice thus express a single MHC class Ia in the absence of all other beta2M
      dependent class Ia and Ib molecules. Following infection with a recombinant
      vaccinia virus expressing a known D(d)-restricted epitope from HIV-1 gp160, the
      development of effector and memory cells CD8 T cells was comparable to control
      mice. Furthermore, these memory cells responded rapidly and robustly to antigenic
      restimulation. Therefore, we conclude that full CD8 memory differentiation
      requires only a single MHC class Ia chain, ruling out a requirement for MHC class
      Ib molecules in this process.

PMID- 16081773
TI  - Both dendritic cells and macrophages can stimulate naive CD8 T cells in vivo to
      proliferate, develop effector function, and differentiate into memory cells.
AB  - The generation of T cell immunity requires the acquisition and presentation of Ag
      on bone marrow-derived APCs. Dendritic cells (DC) are believed to be the most
      potent bone marrow-derived APCs, and the only ones that can stimulate naive T
      cells to productively respond to Ags. Because macrophages (Mphi) are bone marrow
      derived APCs that are also found in tissues and lymphoid organs, can acquire and
      present Ag, and can express costimulatory molecules, we have investigated their
      potential to stimulate primary T cell responses in vivo. We find that both
      injected Mphi and DCs can migrate from peripheral tissues or blood into lymphoid
      organs. Moreover, injection of peptide-pulsed Mphi or DCs into mice stimulates
      CD8 T cells to proliferate, express effector functions including cytokine
      production and cytolysis, and differentiate into long-lived memory cells. Mphi
      and DCs stimulate T cells directly without requiring cross-presentation of Ag on
      host APCs. Therefore, more than one type of bone marrow-derived APC has the
      potential to prime T cell immunity. In contrast, another bone marrow-derived
      cell, the T lymphocyte, although capable of presenting Ag and homing to the T
      cell areas of lymphoid organs, is unable to stimulate primary responses. Because
      Mphi can be very abundant cells, especially at sites of infection and
      inflammation, they have the potential to play an important role in immune
      surveillance and the initiation of T cell immunity.

PMID- 16081774
TI  - A helminth glycan induces APC maturation via alternative NF-kappa B activation
      independent of I kappa B alpha degradation.
AB  - Activation of APCs via TLRs leads to activation of NF-kappaB, a key transcription
      factor in cells of the immune system most often associated with induction of Th1
      type and proinflammatory responses. The neoglycoconjugate lacto-N-fucopentaose
      III (12-25 molecules)-dextran (LNFPIII-Dex) activates dendritic cells (DCs) via
      TLR4, as does LPS. However, unlike LPS, LNFPIII-Dex-activated cells induce Th2
      type CD4+ T cell responses. This observation led us to ask whether LNFPIII
      activated APCs were differentially activating NF-kappaB, and if so, could this
      partly account for how DCs mature in response to these two different pathogen
      associated molecular patterns (PAMPs). In this study, we show that LNFPIII-Dex
      stimulation of APCs induces rapid, but transient NF-kappaB translocation and
      activity in the nucleus, in comparison with the persistent activation induced by
      LPS. We then demonstrate that transient vs persistent NF-kappaB activation has
      important implications in the development of the APC phenotype, showing that the
      second wave of NF-kappaB translocation in response to LPS is required for
      production of the proinflammatory mediator NO. In contrast to LPS, LNFPIII
      stimulated APCs that only transiently activate NF-kappaB do not induce
      degradation of the known IkappaB family members or production of NO. However,
      cells stimulated with LNFPIII rapidly accumulate p50, suggesting that an
      alternative p105 degradation-dependent mechanism is primarily responsible for NF
      kappaB activation downstream of LNFPIII. Finally, we show that while NF-kappaB
      translocation in LNFPIII-stimulated APCs is transient, it is required for the
      development of the DC 2 phenotype, confirming a crucial and multifaceted role for
      NF-kappaB in innate immune responses.

PMID- 16081775
TI  - Invariant NKT cells exacerbate type 1 diabetes induced by CD8 T cells.
AB  - Invariant NKT (iNKT) cells have been implicated in the regulation of autoimmune
      diseases. In several models of type 1 diabetes, increasing the number of iNKT
      cells prevents the development of disease. Because CD8 T cells play a crucial
      role in the pathogenesis of diabetes, we have investigated the influence of iNKT
      cells on diabetogenic CD8 T cells. In the present study, type 1 diabetes was
      induced by the transfer of CD8 T cells specific for the influenza virus
      hemagglutinin into recipient mice expressing the hemagglutinin Ag specifically in
      their beta pancreatic cells. In contrast to previous reports, high frequency of
      iNKT cells promoted severe insulitis and exacerbated diabetes. Analysis of
      diabetogenic CD8 T cells showed that iNKT cells enhance their activation, their
      expansion, and their differentiation into effector cells producing IFN-gamma.
      This first analysis of the influence of iNKT cells on diabetogenic CD8 T cells
      reveals that iNKT cells not only fail to regulate but in fact exacerbate the
      development of diabetes. Thus, iNKT cells can induce opposing effects dependent
      on the model of type 1 diabetes that is being studied. This prodiabetogenic
      capacity of iNKT cells should be taken into consideration when developing
      therapeutic approaches based on iNKT cell manipulation.

PMID- 16081776
TI  - Opposing roles for RelB and Bcl-3 in regulation of T-box expressed in T cells,
      GATA-3, and Th effector differentiation.
AB  - CD4+ T cells with a block in the NF-kappaB signaling pathway exhibit decreases in
      Th1 responses and diminished nuclear levels of multiple transactivating NF
      kappaB/Rel/IkappaB proteins. To determine the lineage-intrinsic contributions of
      these transactivators to Th differentiation, T cells from mice deficient in
      specific subunits were cultured in exogenous cytokines promoting either Th1 or
      Th2 differentiation. RelB-deficient cells exhibited dramatic defects in Th1
      differentiation and IFN-gamma production, whereas no consistent defect in either
      Th1 or Th2 responses was observed with c-Rel-deficient cells. In sharp contrast,
      Bcl-3-null T cells displayed no defect in IFN-gamma production, but their Th2
      differentiation and IL-4, IL-5, and IL-13 production were significantly impaired.
      The absence of RelB led to a dramatic decrease in the expression of T-box
      expressed in T cells and Stat4. In contrast, Bcl-3-deficient cells exhibited
      decreased GATA-3, consistent with evidence that Bcl-3 can transactivate a gata3
      promoter. These data indicate that Bcl-3 and RelB exert distinct and opposing
      effects on the expression of subset-determining transcription factors, suggesting
      that the characteristics of Th cell responses may be regulated by titrating the
      stoichiometry of transactivating NF-kappaB/Rel/IkappaB complexes in the nuclei of
      developing helper effector cells.

PMID- 16081777
TI  - Dendritic cells in human thymus and periphery display a proinsulin epitope in a
      transcription-dependent, capture-independent fashion.
AB  - The natural expression of tissue-specific genes in the thymus, e.g., insulin, is
      critical for self-tolerance. The transcription of tissue-specific genes is
      ascribed to peripheral Ag-expressing (PAE) cells, which discordant studies
      identified as thymic epithelial cells (TEC) or CD11c+ dendritic cells (DC). We
      hypothesized that, consistent with APC function, PAE-DC should constitutively
      display multiple self-epitopes on their surface. If recognized by Abs, such
      epitopes could help identify PAE cells to further define their distribution,
      nature, and function. We report that selected Abs reacted with self-epitopes,
      including a proinsulin epitope, on the surface of CD11c+ cells. We find that
      Proins+ CD11c+ PAE cells exist in human thymus, spleen, and also circulate in
      blood. Human thymic Proins+ cells appear as mature DC but express CD8alpha, CD20,
      CD123, and CD14; peripheral Proins+ cells appear as immature DC. However, DC
      derived in vitro from human peripheral blood monocytes include Proins+ cells that
      uniquely differentiate and mature into thymic-like PAE-DC. Critically, we
      demonstrate that human Proins+ CD11c+ cells transcribe the insulin gene in
      thymus, spleen, and blood. Likewise, we show that mouse thymic and peripheral
      CD11c+ cells transcribe the insulin gene and display the proinsulin epitope;
      moreover, by using knockout mice, we show that the display of this epitope
      depends upon insulin gene transcription and is independent of Ag capturing. Thus,
      we propose that PAE cells include functionally distinct DC displaying self
      epitopes through a novel, transcription-dependent mechanism. These cells might
      play a role in promoting self-tolerance, not only in the thymus but also in the
      periphery.

PMID- 16081778
TI  - Transmembrane sequences are determinants of immunoreceptor signaling.
AB  - To investigate structural features critical for signal initiation by Ag
      stimulated immunoreceptors, we constructed a series of single-chain chimeric
      receptors that incorporate extracellular human Fc epsilonRIalpha for IgE binding,
      a variable transmembrane (TM) segment, and the ITAM-containing cytoplasmic tail
      of the TCR zeta-chain. We find that functional responses mediated by these
      receptors are strongly dependent on their TM sequences, and these responses are
      highly correlated to cross-link-dependent association with detergent-resistant
      lipid rafts. For one chimera designated alpha Fzeta, mutation of a TM cysteine
      abolishes robust signaling and lipid raft association. In addition, TM disulfide
      mediated oligomerization of another chimeric receptor, alpha zetazeta, enhances
      signaling. These results demonstrate an important role for TM segments in
      immunoreceptor signaling and a strong correspondence between strength of
      signaling and cross-link-dependent partitioning into ordered membrane domains.

PMID- 16081779
TI  - Ultraviolet irradiation suppresses T cell activation via blocking TCR-mediated
      ERK and NF-kappa B signaling pathways.
AB  - UV irradiation is carcinogenic and immunosuppressive. Previous studies indicate
      that UV-mediated alteration of APCs and induction of suppressor T cells play a
      critical role in UV-induced immune suppression. In this study, we show that UV
      irradiation can directly (independently of APCs and suppressor T cells) inhibit T
      cell activation by blocking TCR-mediated phosphorylation of ERK and IkappaB via
      overactivation of the p38 and JNK pathways. These events lead to the down
      modulation of c-Jun, c-Fos, Egr-1, and NF-kappaB transcription factors and
      thereby inhibit production of cytokines, e.g., IL-2, IL-4, IFN-gamma, and TNF
      alpha, upon TCR stimulation. We also show that UV irradiation can suppress
      preactivated T cells, indicating that UV irradiation does not only impair T cell
      function in response to T cell activation, but can also have systemic effects
      that influence ongoing immune responses. Thus, our data provide an additional
      mechanism by which UV irradiation directly suppresses immune responses.

PMID- 16081780
TI  - Activation of V gamma 9V delta 2 T cells by NKG2D.
AB  - Human Vgamma9 Vdelta2 T cells recognize phosphorylated nonpeptide Ags (so called
      phosphoantigens), certain tumor cells, and cells treated with
      aminobisphosphonates. NKG2D, an activating receptor for NK cells, has been
      described as a potent costimulatory receptor in the Ag-specific activation of
      gammadelta and CD8 T cells. This study provides evidence that Vgamma9 Vdelta2 T
      cells may also be directly activated by NKG2D. Culture of PBMC with immobilized
      NKG2D-specific mAb or NKG2D ligand MHC class I related protein A (MICA) induces
      the up-regulation of CD69 and CD25 in NK and Vgamma9 Vdelta2 but not in CD8 T
      cells. Furthermore, NKG2D triggers the production of TNF-alpha but not of IFN
      gamma, as well as the release of cytolytic granules by Vgamma9 Vdelta2 T cells.
      Purified Vgamma9 Vdelta2 T cells kill MICA-transfected RMA mouse cells but not
      control cells. Finally, DAP10, which mediates NKG2D signaling in human NK cells,
      was detected in resting and activated Vgamma9 Vdelta2 T cells. These remarkable
      similarities in NKG2D function in NK and Vgamma9 Vdelta2 T cells may open new
      perspectives for Vgamma9 Vdelta2 T cell-based immunotherapy, e.g., by Ag
      independent killing of NKG2D ligand-expressing tumors.

PMID- 16081781
TI  - Characteristics of NK cell migration early after vaccinia infection.
AB  - NK cells are critical components in innate immunity, yet little is known about
      their migration and proliferation during infection. In this report we study the
      early NK response toward vaccinia. We observed NK migration into the infected
      peritoneum as early as 6 h after vaccinia inoculation. Interestingly, although NK
      trafficking to the infected peritoneum depended on G alpha(i) protein-coupled
      receptors, trafficking to other tissues (including lung, liver, spleen, and bone
      marrow) did not. We found that despite a dramatic increase in NK numbers at the
      primary site of infection, their in situ proliferation was low compared with that
      at other tissue locations. These features are similar to those found for Ag
      experienced T cells, suggesting similar patterns of trafficking and proliferation
      for these lymphocyte subsets.

PMID- 16081782
TI  - Redox equilibrium in mucosal T cells tunes the intestinal TCR signaling
      threshold.
AB  - Mucosal immune tolerance in the healthy intestine is typified by lamina propria T
      cell (LPT) functional hyporesponsiveness after TCR engagement when compared with
      peripheral blood T cell (PBT). When LPT from an inflamed intestine are activated
      through TCR cross-linking, their responsiveness is stronger. LPT are thus capable
      of switching from a tolerant to a reactive state, toggling between high and low
      thresholds of activation. We demonstrate that in normal LPT global tyrosine
      phosphorylation upon TCR cross-linking or an increase in intracellular H2O2, an
      inhibitor of protein tyrosine phosphatases, is muted. Thus, we propose that LPT
      have a greater reducing capacity than PBT, shifting the balance between kinases
      and protein tyrosine phosphatases in favor of the latter. Surface gamma-glutamyl
      transpeptidase, an indirect indicator of redox potential, and glutathione are
      significantly elevated in LPT compared with PBT, suggesting that elevated
      glutathione detoxifies TCR-induced reactive oxygen species. When glutathione is
      depleted, TCR-induced LPT tyrosine phosphorylation rises to PBT levels.
      Conversely, increasing glutathione in PBT attenuates tyrosine phosphorylation. In
      LPT isolated from inflamed mucosa, TCR cross-linking induces greater
      phosphorylation, and gamma-glutamyl transpeptidase levels are reduced compared
      with those from autologous noninflamed tissue. We conclude that the high TCR
      signaling threshold of mucosal T cells is tuned by intracellular redox
      equilibrium, whose dysregulation may mediate intestinal inflammation.

PMID- 16081783
TI  - IL-21 enhances tumor rejection through a NKG2D-dependent mechanism.
AB  - IL-21 is a cytokine that can promote the anti-tumor responses of the innate and
      adaptive immune system. Mice treated with IL-21 reject tumor cells more
      efficiently, and a higher percentage of mice remain tumor-free compared with
      untreated controls. In this study, we demonstrate that in certain tumor models IL
      21-enhanced tumor rejection is NKG2D dependent. When engagement of the NKG2D
      receptor was prevented, either due to the lack of ligand expression on the tumor
      cells or due to direct blocking with anti-NKG2D mAb treatment, the protective
      effects of IL-21 treatment were abrogated or substantially diminished.
      Specifically, IL-21 only demonstrated a therapeutic effect in mice challenged
      with a retinoic acid early inducible-1delta-bearing lymphoma but not in mice
      bearing parental RMA tumors lacking NKG2D ligands. Furthermore, treatment with a
      blocking anti-NKG2D mAb largely prevented the therapeutic effect of IL-21 in mice
      challenged with the 4T1 breast carcinoma, the 3LL lung carcinoma, and RM-1
      prostate carcinoma. By contrast, IL-21 did mediate beneficial effects against
      both the parental DA3 mammary carcinoma and DA3 tumors transfected with H60, a
      NKG2D ligand. We also observed that IL-21 treatment could enhance RMA-retinoic
      acid early inducible-1delta tumor rejection in RAG-1(-/-) deficient mice, thereby
      demonstrating that the IL-21-induced protective effect can be mediated by the
      innate immune system and that, in this case, IL-21 does not require the adaptive
      immune response. Collectively, these findings suggest that IL-21 therapy may work
      optimally against tumors that can elicit a NKG2D-mediated immune response.

PMID- 16081784
TI  - Rituximab-induced inhibition of YY1 and Bcl-xL expression in Ramos non-Hodgkin's
      lymphoma cell line via inhibition of NF-kappa B activity: role of YY1 and Bcl-xL
      in Fas resistance and chemoresistance, respectively.
AB  - Rituximab treatment of B non-Hodgkin's lymphoma (NHL) cell lines inhibits the
      constitutive NF-kappaB activity and results in the sensitization of tumor cells
      to both chemotherapy and Fas-induced apoptosis. Cells expressing dominant active
      IkappaB or treated with NF-kappaB-specific inhibitors were sensitive to both
      drugs and Fas agonist mAb (CH-11)-induced apoptosis. Down-regulation of Bcl-xL
      expression via inhibition of NF-kappaB activity correlated with chemosensitivity.
      The direct role of Bcl-xL in chemoresistance was demonstrated by the use of Bcl
      xL-overexpressing Ramos cells, Ramos hemagglutinin (HA)-Bcl-x, which were not
      sensitized by rituximab to drug-induced apoptosis. However, inhibition of Bcl-xL
      in Ramos HA-Bcl-x resulted in sensitization to drug-induced apoptosis. The role
      of Bcl-xL expression in the regulation of Fas resistance was not apparent; Ramos
      HA-Bcl-x cells were as sensitive as the wild type to CH-11-induced apoptosis.
      Several lines of evidence support the direct role of the transcription repressor
      yin-yang 1 (YY1) in the regulation of resistance to CH-11-induced apoptosis.
      Inhibition of YY1 activity by either rituximab or the NO donor DETANONOate or
      after transfection with YY1 small interfering RNA resulted in up-regulation of
      Fas expression and sensitization to CH-11-induced apoptosis. These findings
      suggest two mechanisms underlying the chemosensitization and immunosensitization
      of B-NHL cells by rituximab via inhibition of NF-kappaB. The regulation of
      chemoresistance by NF-kappaB is mediated via Bcl-xL expression, whereas the
      regulation of Fas resistance by NF-kappaB is mediated via YY1 expression and
      activity. The potential clinical significance of these findings is discussed.

PMID- 16081785
TI  - T cell tolerance to germline-encoded antibody sequences in a lupus-prone mouse.
AB  - The BCR V region has been implicated as a potential avenue of T cell help for
      autoreactive B cells in systemic lupus erythematosus. In principle, either
      germline-encoded or somatically generated sequences could function as targets of
      such help. Preceding studies have indicated that class II MHC-restricted T cells
      in normal mice attain a state tolerance to germline-encoded Ab diversity. In this
      study, we tested whether this tolerance is intact in systemic lupus erythematosus
      prone (New Zealand Black x SWR)F1 mice (SNF1). Using a hybridoma sampling
      approach, we found that SNF1 T cells were tolerant to germline-encoded Ab
      sequences. Specifically, they were tolerant to germline-encoded sequences derived
      from a lupus anti-chromatin Ab that arose spontaneously in this strain. This was
      true both for diseased and prediseased mice. Thus, there does not appear to be a
      global defect in T cell tolerance to Ab V regions in this autoimmune-prone strain
      either before or during autoimmune disease.

PMID- 16081786
TI  - A role for IL-27 in early regulation of Th1 differentiation.
AB  - IL-27 is a novel IL-6/IL-12 family cytokine that is considered to play a role in
      Th1 differentiation, whereas the exact role of IL-27 in Th1 differentiation and
      its molecular mechanism remain unclear. In this study we demonstrate a role for
      IL-27 in the early regulation of Th1 differentiation and its possible molecular
      mechanism. The ability of IL-27 to induce Th1 differentiation was most prominent
      under Th1-polarizing conditions, but without IL-12 in a STAT4- and IFN-gamma
      independent manner, and was overruled by IL-12 dose dependently. IL-27 rapidly up
      regulated the expression of ICAM-1 on naive CD4+ T cells, but not on APCs, and
      blocking Abs against ICAM-1 and LFA-1 inhibited the IL-27-induced Th1
      differentiation. Although IL-27 augmented T-bet expression in naive CD4+ T cells
      as previously reported, T-bet was not necessary for the IL-27-induced rapid up
      regulation of ICAM-1 expression and Th1 differentiation. In contrast, STAT1 was
      revealed to be required for the rapid up-regulation of ICAM-1 expression and Th1
      differentiation by directly mediating the transcriptional enhancement of ICAM-1
      gene expression. These results indicate that IL-27 efficiently induces Th1
      differentiation under Th1-polarizing conditions, but without IL-12, and that the
      rapid up-regulation of ICAM-1 expression on naive CD4+ T cells is important for
      the IL-27-induced Th1 differentiation. Considering that IL-27 is produced from
      macrophages and DCs earlier than IL-12, the present results suggest that IL-27
      may play a pivotal role in early efficient induction of Th1 differentiation until
      sufficient IL-12 is produced.

PMID- 16081787
TI  - Lack of ICAM-1 on APCs during T cell priming leads to poor generation of central
      memory cells.
AB  - ICAM-1/LFA-1 interactions are known to enhance T cell/APC interactions and to
      promote T cell activation and cytokine secretion. We have analyzed the
      consequences of ICAM-1-mediated signaling on the generation of memory T cell
      subsets. We report that lack of ICAM-1 on APCs, but not on T cells, leads to poor
      T cell activation and proliferation in vitro and in vivo, and that the defect can
      be compensated by Ag dose, exogenous IL-2, additional costimulation, and by
      increasing responder T cell density on APCs. ICAM-1-null mice do not respond to
      immunization with OVA peptide, but immunization with OVA or with Salmonella
      typhimurium leads to good T cell proliferation 7-10 days later, and clearance of
      a challenge infection is equivalent to that of wild-type mice. However, when
      followed over time, recall proliferation and antibacterial immunity decay rapidly
      in ICAM-1-null mice, while recall cytokine responses are unaffected. The decline
      in immunity is not related to poor survival of T cells activated on ICAM-1-null
      APCs, or to poor generation of effectors in ICAM-1-null mice. Phenotypic analysis
      of T cells stimulated on ICAM-1-null APCs reveals preferential generation of
      CD44(high) CD62L(low) effector memory cells (T(EM)) over CD44(high) CD62L(high)
      central memory cells (T(CM)). Further, while the proportion of naive:memory T
      cells is similar in unmanipulated wild-type and ICAM-1-null mice, there is an
      accumulation of T(EM) cells, and a high T(EM):T(CM) ratio in aging ICAM-1-null
      mice. Together, the data indicate that signaling through LFA-1 during T cell
      activation may be involved in commitment to a proliferation-competent memory
      pool.

PMID- 16081788
TI  - Signaling lymphocyte activation molecule-associated protein is a negative
      regulator of the CD8 T cell response in mice.
AB  - The primary manifestation of X-linked lymphoproliferative syndrome, caused by a
      dysfunctional adapter protein, signaling lymphocyte activation molecule
      associated protein (SAP), is an excessive T cell response upon EBV infection.
      Using the SAP-/- mouse as a model system for the human disease, we compared the
      response of CD8+ T cells from wild-type (wt) and mutant mice to various stimuli.
      First, we observed that CD8+ T cells from SAP-/- mice proliferate more vigorously
      than those from wt mice upon CD3/CD28 cross-linking in vitro. Second, we analyzed
      the consequence of SAP deficiency on CTL effector function and homeostasis. For
      this purpose, SAP-/- and wt mice were infected with the murine gamma-herpesvirus
      68 (MHV-68). At 2 wk postinfection, the level of viral-specific CTL was much
      higher in mutant than in wt mice, measured both ex vivo and in vivo. In addition,
      we established that throughout 45 days of MHV-68 infection the frequency of virus
      specific CD8+ T cells producing IFN-gamma was significantly higher in SAP-/-
      mice. Consequently, the level of latent infection by MHV-68 was considerably
      lower in SAP-/- mice, which indicates that SAP-/- CTL control this infection more
      efficiently than wt CTL. Finally, we found that the Vbeta4-specific CD8+ T cell
      expansion triggered by MHV-68 infection is also enhanced and prolonged in SAP-/-
      mice. Taken together, our data indicate that SAP functions as a negative
      regulator of CD8+ T cell activation.

PMID- 16081789
TI  - Prolongation of sheep corneal allograft survival by transfer of the gene encoding
      ovine IL-12-p40 but not IL-4 to donor corneal endothelium.
AB  - Immunological rejection is the major cause of human corneal allograft failure. We
      hypothesized that local production of IL-4 or the p40 subunit of IL-12 (p40 IL
      12) by the grafted cornea might prolong allograft survival. Replication-deficient
      adenoviral vectors encoding ovine IL-4 or p40 IL-12 and GFP were generated and
      used to infect ovine corneas ex vivo. mRNA for each cytokine was detected in
      infected corneas, and the presence of secreted protein in corneal supernatants
      was confirmed by bioassay (for IL-4) or immunoprecipitation (for p40 IL-12).
      Sheep received uninfected or gene-modified orthotopic corneal allografts.
      Postoperatively, untreated corneas (n = 13) and corneas expressing GFP (n = 6)
      were rejected at a median of 21 and 20 days, respectively. Corneas expressing IL
      4 (n = 6) underwent rejection at 18.5 days (p > 0.05 compared with controls) and
      histology demonstrated the presence of eosinophils. In contrast, corneas
      expressing p40 IL-12 (n = 9) showed prolonged allograft survival (median day to
      rejection = 45 days, p = 0.003). Local intraocular production of p40 IL-12 thus
      prolonged corneal graft survival significantly, but local production of the
      prototypic immunomodulatory cytokine IL-4 induced eosinophilia, inflammation, and
      rejection. These findings have important implications for the development of
      novel strategies to improve human corneal graft survival.

PMID- 16081790
TI  - Pulmonary surfactant protein A activates a phosphatidylinositol 3-kinase/calcium
      signal transduction pathway in human macrophages: participation in the up
      regulation of mannose receptor activity.
AB  - Surfactant protein A (SP-A), a major component of lung surfactant, binds to
      macrophages and has been shown to alter several macrophage biological functions,
      including up-regulation of macrophage mannose receptor (MR) activity. In the
      present study, we show that SP-A induces signal transduction pathway(s) that
      impact on MR expression. The addition of human, rat, or recombinant rat SP-A to
      human monocyte-derived macrophages significantly raised the level of cytosolic
      Ca2+ above baseline within 10 s of SP-A addition, as measured by
      spectrofluorometric analysis. SP-A induced a refractory state specific for SP-A
      consistent with homologous desensitization of a receptor(s) linked to calcium
      mobilization because a second application of SP-A did not induce a rise in
      cytosolic Ca2+ whereas the addition of platelet-activating factor did. Using site
      directed mutations in SP-A, we determined that both the attached sugars and the
      collagen-like domain of SP-A are necessary to optimize Ca2+ mobilization. SP-A
      triggered the increase in cytosolic Ca2+ by inducing activation of phospholipase
      C, which leads to the hydrolysis of membrane phospholipids, yielding inositol
      1,4,5-trisphosphate and mobilizing intracellularly stored Ca2+ by inositol
      triphosphate-sensitive channels. Finally, inhibition of PI3Ks, which appear to
      act upstream of phospholipase C in Ca2+ mobilization, decreased the SP-A-induced
      rise in MR expression, providing evidence that SP-A induction of MR activity
      involves the activation of a pathway in which PI3K is a component. These studies
      provide further evidence that SP-A produced in the lung plays a role in
      modulating macrophage biology, thereby contributing to the alternative activation
      state of the alveolar macrophage.

PMID- 16081791
TI  - Proteomic analysis of microglia-derived exosomes: metabolic role of the
      aminopeptidase CD13 in neuropeptide catabolism.
AB  - Vesicle transport is a fundamental mechanism of communication in the CNS. In this
      study we characterized a novel type of vesicle released by murine brain
      microglial cells: microglial exosomes. Analysis of their protein content
      identified several enzymes, chaperones, tetraspanins, and membrane receptors
      previously reported in B cells and dendritic cell-derived exosomes. Additionally,
      microglia-derived exosomes expressed the aminopeptidase CD13 and the lactate
      transporter MCT-1. Exosomal CD13 was metabolically active in cleaving leucine-
      and methionine-enkephalins peptides by releasing the N-terminal tyrosine. Cleaved
      neuropeptides were unable to bind to the neuronal opioid receptor as assessed by
      cAMP response. Microglial exosomal vesicles may represent an important,
      previously unrecognized, cellular communication system in an organ in which cell
      motility is highly restricted.

PMID- 16081792
TI  - Enhancement of dendritic cell antigen cross-presentation by CpG DNA involves type
      I IFN and stabilization of class I MHC mRNA.
AB  - Dendritic cells (DCs) internalize exogenous Ags and process them for cross
      presentation by class I MHC (MHC-I) to CD8+ T cells. This processing can occur by
      transporter for Ag presentation (TAP)-dependent or TAP-independent mechanisms. We
      observed that CpG DNA enhanced cross-presentation of Ags by Flt-3L-cultured bone
      marrow-derived murine DCs by a type I IFN (IFN-alphabeta)-dependent mechanism.
      Myeloid DCs provided cross-presentation function in this system. Both TAP1
      knockout and wild-type DCs showed enhanced cross-presentation when treated with
      CpG DNA at 26 degrees C, demonstrating that TAP is not essential to this
      regulatory mechanism, although TAP is an important determinant of MHC-I
      expression. Enhancement of cross-processing by CpG DNA did not involve increased
      Ag uptake or proteolysis but did correlate with IFN-alphabeta-dependent increases
      in expression of MHC-I mRNA and protein. Increased MHC-I mRNA levels resulted in
      part from stabilization of MHC-I mRNA, a novel posttranscriptional mechanism for
      regulation of MHC-I expression. Thus, a major mechanism by which CpG
      oligodeoxynucleotide increase cross presentation by DCs appears to be an IFN
      alphabeta-mediated increase in MHC-I synthesis.

PMID- 16081793
TI  - Insertion of the dibasic motif in the flanking region of a cryptic self
      determinant leads to activation of the epitope-specific T cells.
AB  - Efficient induction of self tolerance is critical for avoiding autoimmunity. The
      T cells specific for the well-processed and -presented (dominant) determinants of
      a native self protein are generally tolerized in the thymus, whereas those
      potentially directed against the inefficiently processed and presented (cryptic)
      self epitopes escape tolerance induction. We examined whether the crypticity of
      certain determinants of mouse lysozyme-M (ML-M) could be attributed to the
      nonavailability of a proteolytic site, and whether it could be reversed to
      immunodominance by engraftment of a novel cleavage site in the flanking region of
      the epitope. Using site-directed mutagenesis, we created the dibasic motif (RR or
      RK; R = arginine, K = lysine), a target of intracellular proteases, in the region
      adjoining one of the three cryptic epitopes (46-61, 66-79, or 105-119) of ML-M.
      Interestingly, the mutated lysozyme proteins, but not unmutated ML-M, were
      immunogenic in mice. The T cell response to the altered lysozyme was attributable
      to the efficient processing and presentation of the previously cryptic epitope,
      and this response was both epitope and MHC haplotype specific. In addition, the
      anti-self T cell response was associated with the generation of autoantibodies
      against self lysozyme. However, the results using one of three mutated lysozymes
      suggested that the naturally processed, dibasic motif-marked epitope may not
      always correspond precisely to the cryptic determinant within a synthetic
      peptide. This is the first report describing the circumvention of self tolerance
      owing to the targeted reversal of crypticity to dominance in vivo of a specific
      epitope within a native self Ag.

PMID- 16081794
TI  - IL-21 influences the frequency, phenotype, and affinity of the antigen-specific
      CD8 T cell response.
AB  - IL-21, a newly described cytokine belonging to the IL-2 gamma-chain receptor
      cytokine family (that includes IL-2, IL-7, and IL-15), has been described as an
      important regulator of the cellular immune response. In this study, the role of
      IL-21 in the generation of a human Ag-specific CD8+ T cell response is
      characterized by tracking a rare, but measurable population of self-Ag-specific T
      cells in vitro. Autologous dendritic cells pulsed with the melanoma antigen
      recognized T cells 1 self-peptide were used to stimulate CD8+ T cells from HLA
      A2+ healthy donors and melanoma patients. We demonstrate that exposure to IL-21
      increased the total number of MART-1-specific CD8+ T cells that could be elicited
      by >20-fold and, at the clonal level, enriched for a population of high-affinity
      CD8+ T cells with a peptide dose requirement more than 1 log(10)-fold less than
      their untreated counterparts. Phenotypic analysis of T cells from IL-21-treated
      cultures revealed a unique population of CD45RO+ CD28(high) CD8+ T cells, a
      phenotype that was stable for at least 4 wk after IL-21 exposure. These
      CD28(high) CD8+ T cells produced IL-2 upon Ag stimulation and represent potential
      helper-independent CTLs. Our studies demonstrate a significant role for IL-21 in
      the primary Ag-specific human CTL response and support the use of IL-21 in the ex
      vivo generation of potent Ag-specific CTLs for adoptive therapy or as an adjuvant
      cytokine during in vivo immunization against tumor Ags.

PMID- 16081795
TI  - Control of recent thymic emigrant survival by positive selection signals and
      early growth response gene 1.
AB  - Early growth response gene 1 (Egr1) is a transcriptional regulator whose
      expression can be induced by multiple signals including the TCR. Egr1 has been
      shown to promote positive selection, but an investigation of its role in T cell
      homeostasis has not been reported. The possibility that similar signals control
      both positive selection and peripheral T cell homeostasis led us to investigate
      the role of Egr1 in the maintenance of peripheral T cells. We have found that on
      TCR transgenic backgrounds, Egr1-deficient mice have a reduction in their number
      of naive T cells. Although Egr1-deficient animals have a low percentage of mature
      thymocytes due to inefficient positive selection, the absolute number of mature
      thymocytes is only slightly reduced due to increased thymus size in Egr1
      deficient mice. Despite possessing near normal numbers of mature thymocytes, we
      find that Egr1-deficient mice have poor accumulation of recent thymic emigrants
      (RTE) in the periphery. The poor accumulation of RTE in Egr1-deficient mice
      appears to originate from decreased survival of mature thymocytes and RTE, which
      we have observed both in vitro and in vivo. These findings suggest that an Egr1
      mediated signal during positive selection promotes not only the production of
      single positive thymocytes, but also the survival of selected thymocytes until
      they can become established in the periphery.

PMID- 16081796
TI  - Novel ganglioside antigen identified by B cells in human medullary breast
      carcinomas: the proof of principle concerning the tumor-infiltrating B
      lymphocytes.
AB  - The potential tumor-recognizing capacity of B cells infiltrating human breast
      carcinoma is an important aspect of breast cancer biology. As an experimental
      system, we used human medullary breast carcinoma because of its heavy B
      lymphocytic infiltration paralleled to a relatively better prognosis. Ig
      rearranged V region V(H)-J(H), Vkappa-Jkappa, and Vlambda-Jlambda genes,
      amplified by RT-PCR of the infiltrating B cells, were cloned, sequenced, and
      subjected to a comparative DNA analysis. A combinatorial single-chain variable
      fragment Ab minilibrary was constructed out of randomly selected V(H) and Vkappa
      clones and tested for binding activity. Our data analysis revealed that some of
      the V(H)-J(H), Vkappa-Jkappa, and Vlambda-Jlambda region sequences were being
      assigned to clusters with oligoclonal predominance, while other characteristics
      of the Ab repertoire were defined also. A tumor-restricted binder clone could be
      selected out of the single-chain variable fragment kappa minilibrary tested
      against membrane fractions of primary breast tumor cells and tumor cell lines,
      the V(H) of which proved to be the overexpressed V(H)3-1 cluster. The specific
      binding was confirmed by FACS analysis with primary breast carcinoma cells and
      MDA-MB 231 cell line. ELISA and thin layer chromatography dot-blot experiments
      showed this target Ag to be a ganglioside D3 (GD3). Our results are a proof of
      principle about the capacity of B cells infiltrating breast carcinomas to reveal
      key cancer-related Ags, such as the GD3. GD3-specific Abs may influence tumor
      cell progression and could be used for further development of diagnostic and/or
      therapeutic purposes.

PMID- 16081797
TI  - Resistance to myelin oligodendrocyte glycoprotein-induced experimental autoimmune
      encephalomyelitis by death receptor 6-deficient mice.
AB  - Genetic disruption of death receptor 6 (DR6) results in enhanced CD4+ T cell
      expansion, Th2 differentiation, and humoral responses after stimulation. However,
      the in vivo consequences of DR6 targeting (DR6-/-) during the initiation and
      progression of inflammatory autoimmune disease are unclear. Using a myelin
      oligodendrocyte glycoprotein (MOG(35-55))-induced model of experimental
      autoimmune encephalomyelitis, DR6-/- mice were found to be highly resistant to
      both the onset and the progression of CNS disease compared with wild-type (WT)
      littermates. DR6-/- mice exhibited fewer inflammatory foci along with minimal
      demyelination and perivascular cuffing of inflammatory cells. Consistent with
      these observations, mononuclear cell infiltration, including CD4+ T cells and
      macrophages, in the spinal cord of DR6-/- mice was dramatically reduced.
      Furthermore, CD4+ T cells from DR6-/- mice exhibited profoundly reduced cell
      surface expression of VLA-4 before and after stimulation. Compared with WT mice,
      DR6-/- mice exhibited significantly increased autoantigen-induced T cell
      proliferative responses along with greater numbers of IL-4-producing and similar
      or slightly higher numbers of IFN-gamma-producing CD4+ T cells. DR6-/- CD4+ T
      cells secreted higher levels of the Th2 cytokine, IL-4, and similar levels of the
      Th1 cytokine, IFN-gamma, compared with WT cells. Taken together, our data
      demonstrate that DR6 plays an important role in regulating leukocyte infiltration
      and function in the induction and progression of experimental autoimmune
      encephalomyelitis.

PMID- 16081798
TI  - Specific inhibition of c-Raf activity by semapimod induces clinical remission in
      severe Crohn's disease.
AB  - There is a substantial need for novel treatment strategies in Crohn's disease
      (CD), a chronic relapsing inflammatory disease of the gut. In an earlier study,
      we reported clinical efficacy of a 2-wk treatment with semapimod (CNI-1493) in 12
      patients with therapy resistant CD. The aim of this study was to identify the
      cellular target underlying semapimod action. In vitro experiments with murine
      macrophages showed impaired MAPK signaling and decreased cytokine production due
      to semapimod treatment. In vitro kinase assays revealed c-Raf as a direct
      molecular target of semapimod, and semapimod did not affect b-Raf enzymatic
      activity. Immunohistochemistry performed on paired colon biopsies obtained from
      CD patients (n = 6) demonstrated increased expression of phospho-MEK, the
      substrate of Raf. Strikingly, phospho-MEK levels were significantly decreased in
      patients with a good clinical response to semapimod, but no decrease in phospho
      MEK expression was observed in a clinically nonresponsive patient. In conclusion,
      this study identifies c-Raf as a molecular target of semapimod action and
      suggests that decreased c-Raf activity correlates with clinical benefit in CD.
      Our observations indicate that c-Raf inhibitors are prime candidates for the
      treatment of CD.

PMID- 16081799
TI  - Expression and function of glial cell line-derived neurotrophic factor family
      ligands and their receptors on human immune cells.
AB  - There is increasing evidence that factors originally identified due to their
      neurotrophic activity also function within the immune system. This study focused
      on the related molecules glial cell line-derived neurotrophic factor (GDNF) and
      neurturin (NTN) as well as their receptors. GDNF and NTN signaling is mediated by
      a two-component receptor: a signal-transducing component, RET, which is shared by
      both ligands, and a ligand-specific binding component, GFR alpha-1 (higher GDNF
      affinity) or GFR alpha-2 (higher NTN affinity). We report that human T cells, B
      cells, and monocytes produce NTN but not GDNF, as seen by RT-PCR and
      immunocytochemistry. RET was expressed by B cells, T cells, and monocytes. Exons
      2-5 of RET encoding the cadherin-like domains 1-3 in the extracellular part and
      exons 16-19 encoding a section of the second tyrosine kinase domain were
      transcribed in CD4+ T cells, CD8+ T cells, B cells, and monocytes. Different
      splice variants encoding the C-terminal intracellular part (exons 19-21) of RET
      were detected. The ligand-binding receptors GFR alpha-1 and GFR alpha-2 were
      transcribed in all immune cell subsets. Quantitative PCR showed that GFR alpha-2
      is by far the dominant ligand binding chain in T cells, B cells, and monocytes.
      Addition of GDNF or NTN to activated PBMCs reduced the amount of detectable TNF
      protein without altering its transcription. Together, this suggests that immune
      cells communicate with each other via NTN. Production of NTN by immune cells
      might also contribute to the neuroprotective immunity in the CNS observed in
      different model systems.

PMID- 16081800
TI  - MHC-mismatched islet allografts are vulnerable to autoimmune recognition in vivo.
AB  - When transplanted into type 1a diabetic recipients, islet allografts are subject
      both to conventional allograft immunity and, presumably, to recurrent autoimmune
      (islet-specific) pathogenesis. Importantly, CD4 T cells play a central role both
      in islet allograft rejection and in autoimmune disease recurrence leading to the
      destruction of syngeneic islet transplants in diabetic NOD mice. However, it is
      unclear how NOD host MHC class II (I-A(g7))-restricted, autoreactive CD4 T cells
      may also contribute to the recognition of allogeneic islet grafts that express
      disparate MHC class II molecules. We hypothesized that islet-specific CD4 T cells
      can target MHC-mismatched islet allografts for destruction via the "indirect"
      (host APC-dependent) pathway of Ag recognition. To test this hypothesis, we
      determined whether NOD-derived, islet-specific CD4 T cells (BDC-2.5 TCR
      transgenic cells) could damage MHC-mismatched islets in vivo independent of
      conventional allograft immunity. Results demonstrate that BDC-2.5 CD4 T cells can
      vigorously destroy MHC class II-disparate islet allografts established in
      NOD.scid recipients. Tissue injury is tissue-specific in that BDC-2.5 T cells
      destroy donor-type islet, but not thyroid allografts established in the same
      NOD.scid recipient. Furthermore, BDC-2.5 CD4 T cells acutely destroy MHC class II
      deficient islet allografts in vivo, indicating that autoimmune pathogenesis can
      be completely independent of donor MHC class II expression. Taken together, these
      findings indicate that MHC-mismatched islet allografts can be vulnerable to
      autoimmune pathogenesis triggered by autoreactive CD4 T cells, presumably through
      indirect autoantigen recognition in vivo.

PMID- 16081801
TI  - Changes in replication, nuclear location, and expression of the Igh locus after
      fusion of a pre-B cell line with a T cell line.
AB  - We have previously observed that replication and nuclear location of the murine
      Igh locus are developmentally regulated during B cell differentiation. In non-B,
      B, and plasma cells, sequences near the 3' end of the Igh locus replicate early
      in S while upstream Vh sequences replicate late in S, and the Igh locus is
      located near the nuclear periphery. In fact, in MEL non-B cells, replication of a
      500-kb segment containing Igh-C and flanking sequences occurs progressively later
      throughout S by 3' to 5' unidirectional fork movement. In contrast, in pro- and
      pre-B cells, the entire 3-Mb Igh locus is located away from the nuclear periphery
      and replicates early in S by forks progressing in both directions. In this study,
      using an 18-81 (pre-B) x BW5147 (T) cell fusion system in which Igh expression is
      extinguished, we found that in all Igh alleles, Vh sequences replicated later in
      S than 3' Igh sequences (similar to that detected in BW5147), but the Igh locus
      was situated away from the nuclear periphery (similar to that observed in 18-81).
      Thus, pre-B cell-derived Igh genes had changes in replication timing, but not in
      nuclear location, whereas T cell-derived Igh genes changed their nuclear location
      but not their replication timing. These data are consistent with the silencing of
      a pre-B cell-specific replication program in the fusion hybrid cells and
      independent regulation of the nuclear location of Igh loci.

PMID- 16081802
TI  - Up-regulation of IL-7, stromal-derived factor-1 alpha, thymus-expressed
      chemokine, and secondary lymphoid tissue chemokine gene expression in the stromal
      cells in response to thymocyte depletion: implication for thymus reconstitution.
AB  - Three in vivo adult mouse models were established to study which signals are
      required to restore the postnatal thymus. Single administration of dexamethasone,
      estradiol, or exposure to sublethal dose of gamma irradiation served as prototype
      thymus-ablating therapies. In all models, transient thymic atrophy was manifested
      due to the loss of the predominant portion of CD4- CD8- double negative and CD4+
      CD8+ double positive thymocytes and was followed by a complete regeneration of
      the thymuses. Acute atrophy/regeneration was observed in the dexamethasone and
      irradiation models; in the estradiol-treated animals, slow kinetics of atrophy
      and regeneration was observed. Importantly, in both acute and chronic models,
      high levels of IL-7 mRNA were detected in the thymuses isolated from mice during
      maximum atrophy. In addition, chemokine gene array analysis of involuted thymuses
      revealed high levels of mRNA expression of stromal-derived factor-1alpha (SDF
      1alpha), thymus-expressed chemokine (TECK), and secondary lymphoid tissue
      chemokine (SLC) but not of other chemokines. The levels of IL-7, SDF-1alpha,
      TECK, and SLC mRNA inversely correlated with the kinetics of regeneration. RT-PCR
      analysis of stromal cells purified from involuted thymuses confirmed increased IL
      7, SDF-1alpha, and SLC gene expression in MHC class II+ CD45- epithelial cells
      and increased IL-7 and TECK gene expression in class II+ CD45+ CD11c+ dendritic
      cells. Thus, our data showed for the first time that expression of IL-7, SDF
      1alpha, TECK, and SLC mRNA is induced in the thymic stroma during T cell
      depletion and may play an important role in the reconstitution of the adult
      thymus.

PMID- 16081803
TI  - A novel Fc gamma R-defined, IgG-containing organelle in placental endothelium.
AB  - Placental transfer of IgG from maternal circulation to that of the fetus is
      crucial for fetal and newborn immunity. This process requires that IgG broach two
      cellular layers of the placenta. IgG transport across the first layer, the
      syncytiotrophoblast, is almost certainly mediated by the MHC-related FcR for IgG,
      FcRn. The second layer, the villus endothelium, was until recently thought to
      allow IgG movement nonspecifically by constitutive transcytosis in caveolae.
      However, we recently showed that villus endothelium expressed a separate FcR for
      IgG, the inhibitory motif-bearing Fc gammaRIIb2 seen most notably on macrophages
      and as a minor fraction of the Fc gammaRIIb expressed on B cells. Now, by
      quantitative microscopy, we find Fc gammaRIIb2 to be expressed abundantly in an
      unidentifiable and likely novel organelle of the villus endothelium, unassociated
      with caveolae. About half of these Fc gammaRIIb2 organelles contain IgG; the
      remainder lack IgG. The majority fraction (approximately 80%) of IgG-containing
      organelles is associated with Fc gammaRIIb. No IgG-containing organelles are
      associated with caveolin. These findings are compatible with Fc gammaRIIb
      mediated transfer of IgG across the villus endothelium, independent of caveolae.

PMID- 16081804
TI  - The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo.
AB  - ICOS is a new member of the CD28 family of costimulatory molecules that is
      expressed on activated T cells. Its ligand B7RP-1 is constitutively expressed on
      B cells. Although the blockade of ICOS/B7RP-1 interaction inhibits T cell
      dependent Ab production and germinal center formation, the mechanism remains
      unclear. We examined the contribution of ICOS/B7RP-1 to the generation of CXCR5+
      follicular B helper T (T(FH)) cells in vivo, which preferentially migrate to the
      B cell zone where they provide cognate help to B cells. In the spleen, anti-B7RP
      1 mAb-treated or ICOS-deficient mice showed substantially impaired development of
      CXCR5+ T(FH) cells and peanut agglutinin+ germinal center B cells in response to
      primary or secondary immunization with SRBC. Expression of CXCR5 on CD4+ T cells
      was associated with ICOS expression. Adoptive transfer experiments showed that
      the development of CXCR5+ T(FH) cells was enhanced by interaction with B cells,
      which was abrogated by anti-B7RP-1 mAb treatment. The development of CXCR5+ T(FH)
      cells in the lymph nodes was also inhibited by the anti-B7RP-1 mAb treatment.
      These results indicated that the ICOS/B7RP-1 interaction plays an essential role
      in the development of CXCR5+ T(FH) cells in vivo.

PMID- 16081805
TI  - CC chemokine ligand 19 secreted by mature dendritic cells increases naive T cell
      scanning behavior and their response to rare cognate antigen.
AB  - For immune responses to take place, naive T cells have to encounter, adhere to,
      and be stimulated by dendritic cells (DCs). In murine lymph nodes, T cells move
      randomly and scan the surface of multiple DCs. The factors controlling this
      motility as well as its consequences remain unclear. We have monitored by video
      imaging the earliest steps of the interaction between human DCs and autologous
      naive CD4+ T cells in the absence of exogenous Ags. Mature, but not immature, DCs
      were able to elicit small calcium responses in naive T cells along with cell
      polarization and random motility, resulting in an efficient scanning of DC
      surfaces by T cells. We identified CCL19 as a key factor enabling all these early
      T cell responses, including the occurrence of calcium transients. Because this
      chemokine did not influence the strength of naive T cell adhesion to DCs,
      enhanced LFA-1 affinity for ICAM-1 was not the main mechanism by which CCL19
      increased Ag-independent calcium transients. However, concomitantly to T cell
      motility, CCL19 augmented the frequency of T cell responses to rare anti-CD3/CD28
      coated beads, used as surrogate APCs. We thus propose a new role for CCL19 in
      humans: by conditioning T cells into a motile DC-scanning state, this chemokine
      promotes Ag-independent responses and increases the probability of cognate MHC
      peptide encounter.

PMID- 16081806
TI  - Coordinate analysis of murine immune cell surface markers and intracellular
      phosphoproteins by flow cytometry.
AB  - Recently, phosphospecific flow cytometry has emerged as a powerful tool to
      analyze intracellular signaling events in complex populations of cells because of
      its ability to simultaneously discriminate cell types based on surface marker
      expression and measure levels of intracellular phosphoproteins. This has provided
      novel insights into the cell- and pathway-specific nature of immune signaling.
      However, we and others have found that the fixation and permeabilization steps
      necessary for phosphoprotein analysis often negatively affect the resolution of
      cell types based on surface marker analysis and light scatter characteristics.
      Therefore, we performed a comprehensive profile of >35 different murine surface
      marker Abs to understand the effects of fixation and permeabilization on surface
      Ag staining. Fortuitously, approximately 80% of the Abs tested resolved cell
      populations of interest, although with decreased separation between positive and
      negative populations and at very different titers than those used on live cells.
      The other 20% showed either complete loss of separation between populations or
      loss of intermediately staining populations. We were able to rescue staining of
      several of these Ags by performing staining after fixation, but before
      permeabilization, although with limited fluorophore choices. Scatter
      characteristics of lymphocytes were well retained, but changed dramatically for
      monocyte and neutrophil populations. These results compile a comprehensive
      resource for researchers interested in applying phosphospecific flow cytometry to
      complex populations of cells while outlining steps necessary to successfully
      apply new surface marker Abs to this platform.

PMID- 16081807
TI  - Characterization of the murine immunological signaling network with
      phosphospecific flow cytometry.
AB  - The immune system is a multitiered network that at the first level uses changes
      to intracellular signaling proteins to commit cells to determined fates. At the
      second tier, cells interact with one another via specifically expressed surface
      receptors and their cognate signaling molecules. At the third level, the local
      environments of immune cells change the outcomes of intracellular signaling
      pathways and thereby the role of cells during immune challenge. The interplay
      among these three tiers allows the distinct cell types of the immune system to
      respond cohesively to eliminate foreign Ags. In this study, using phosphospecific
      flow cytometry, we analyze elements of these network tiers by generating profiles
      of single-cell phosphoprotein responses in B cells, T cells, and myeloid cells to
      a number of mechanistically and clinically relevant cytokines (IFN-gamma, GM-CSF,
      IL-2, and IL-10) as well as LPS at key regulatory interfaces (Jak-Stat and MAPK
      pathways). The stimuli typically induced phosphorylation of specific signaling
      pathways and exerted their effects on distinct subsets of immune cells. However,
      upon comparison of stimulation in vitro and in vivo, we noted that signaling
      pathway specificity and cell type specificity were influenced strongly by the
      external environment. When taken from the in vivo environment, certain cell
      subsets became hypo- or hyper-responsive, showed profound differences in
      sensitivity to cytokine levels, or displayed altered phosphorylation kinetics.
      Thus, simultaneous analysis of the three tiers of the immune system network
      illustrates the principles by which immune regulation is context dependent and
      how in vitro culture systems compare with the in vivo environment.

PMID- 16081808
TI  - ERK1-deficient mice show normal T cell effector function and are highly
      susceptible to experimental autoimmune encephalomyelitis.
AB  - T cell activation engages multiple intracellular signaling cascades, including
      the ERK1/2 (p44/p42) pathway. It has been suggested that ERKs integrate TCR
      signal strength, and are important for thymocyte development and positive
      selection. However, the requirement of ERKs for the effector functions of
      peripheral mature T cells and, specifically, for T cell-mediated autoimmunity has
      not been established. Moreover, the specific requirements for ERK1 vs ERK2 in T
      cells have not been resolved. Therefore, we investigated the role of ERK1 in T
      cell immunity to foreign and self Ags and in the induction of experimental
      autoimmune encephalomyelitis. The results show that in ERK1-deficient (ERK1-/-)
      mice, the priming, proliferation, and cytokine secretion of T cells to the self
      Ag myelin oligodendrocyte glycoprotein peptide 35-55 and to the prototypic
      foreign Ag OVA are not impaired as compared with wild-type mice. Furthermore,
      ERK1-/- mice are highly susceptible to experimental autoimmune encephalomyelitis
      induced with myelin oligodendrocyte glycoprotein peptide 35-55. Finally,
      thymocyte development and mitogen-induced proliferation were not impaired in ERK1
      /- mice on the inbred 129 Sv and C57BL/6 backgrounds. Collectively, the data show
      that ERK1 is not critical for the function of peripheral T cells in the response
      to self and foreign Ags and in T cell-mediated autoimmunity, and suggest that its
      loss can be compensated by ERK2.

PMID- 16081809
TI  - Isoform-specific membrane targeting mechanism of Rac during Fc gamma R-mediated
      phagocytosis: positive charge-dependent and independent targeting mechanism of
      Rac to the phagosome.
AB  - Rac1 and Rac2 are capable of stimulating superoxide production in vitro, but
      their targeting and functional mechanisms are still unknown. In the present
      study, we found that Rac1, 2, and 3 all accumulate at the phagosome during Fc
      gammaR-mediated phagocytosis, and that the order of accumulation (Rac1 > Rac3 >
      Rac2) depends on the net positive charge in their polybasic (PB) regions (183-188
      aa). Although all GFP-tagged prenylated PB regions of Rac isoforms (GFP-Rac(PB))
      and GFP-tagged prenylated 6 Ala (GFP-6A) accumulated during phagocytosis, GFP
      Rac2(PB) and GFP-6A showed weak accumulation at the phagosome through a linear
      structure connecting the phagosome and endomembranes. The PB region of Rac1
      showed strong phospholipid interaction with PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P3,
      and phosphatidic acid, however, that of Rac2 did not. Constitutively active Rac2,
      GFP-Rac2(Q61L), was predominantly localized at the endomembranes; these
      endomembranes fused to the phagosome through the linear structure during
      phagocytosis, and this accumulation mechanism did not depend on positive charge
      in the PB region. Our conclusion is that Rac1 directly targets to the phagosome
      using the positively charged PB region and this accumulation mechanism is likely
      enhanced by the phospholipids. In addition to this mechanism, Rac2 has a positive
      charge-independent mechanism in which Rac2 initially targets to endomembranes and
      then these endomembranes fuse to the phagosome.

PMID- 16081810
TI  - Systemic autoimmune disease caused by autoreactive B cells that receive chronic
      help from Ig V region-specific T cells.
AB  - B cells present BCR V region-derived Id-peptides on their MHC class II molecules
      to Id-specific CD4+ T cells. Prolonged Id-driven T-B collaboration could cause
      autoimmune disease, but this possibility is difficult to test in normal
      individuals. We have investigated whether mice doubly transgenic for an Id+ Ig L
      chain and an Id-specific TCR develop autoimmune disease. Surprisingly, T cell
      tolerance was not complete in these mice because a low frequency of weakly Id
      reactive CD4+ T cells accumulated with age. These escapee Id-specific T cells
      provided chronic help for Id+ B cells, resulting in a lethal systemic autoimmune
      disease including germinal center reactions, hypergammaglobulinemia, IgG
      autoantibodies, glomerulonephritis, arthritis, skin affection, and inflammatory
      bowel disease. Inflamed tissues contained foci of Id-driven T-B collaboration,
      with deposition of IgG and complement. The disease could be transferred with B
      and T cells. The results demonstrate a novel mechanism for development of
      autoimmune disease in which self-reactive Id+ B cells receive prolonged help from
      Id-specific T cells, thus bypassing the need for help from T cells recognizing
      conventional Ag.

PMID- 16081811
TI  - Exacerbation of experimental allergic asthma by augmented Th2 responses in WSX-1
      deficient mice.
AB  - WSX-1 (IL-27R) is a class I cytokine receptor with homology to gp130 and IL-12
      receptors and is typically expressed on CD4+ T lymphocytes. Although previous
      reports have clarified that IL-27/WSX-1 signaling plays critical roles in both
      Th1 differentiation and attenuation of cell activation and proinflammatory
      cytokine production during some bacterial or protozoan infections, little is
      known about the importance of WSX-1 in cytokine-mediated diseases of allergic
      origin. To this aim, we took advantage of WSX-1-deficient (WSX-1(-/-)) mice and
      induced experimental asthma, in which Th2 cytokines are central modulators of the
      pathology. OVA-challenged WSX-1(-/-) mice showed marked enhancement of airway
      responsiveness with goblet cell hyperplasia, pulmonary eosinophil infiltration,
      and increased serum IgE levels compared with wild-type mice. Production of Th2
      cytokines, which are largely responsible for the pathogenesis of asthma, was
      augmented in the lung or in the culture supernatants of peribronchial lymph node
      CD4+ T cells from WSX-1(-/-) mice compared with those from wild-type mice.
      Surprisingly, IFN-gamma production was also enhanced in WSX-1(-/-) mice, albeit
      at a low concentration. The cytokine overproduction, thus, seems independent from
      the Th1-promoting property of WSX-1. These results demonstrated that IL-27/WSX-1
      also plays an important role in the down-regulation of airway hyper-reactivity
      and lung inflammation during the development of allergic asthma through its
      suppressive effect on cytokine production.

PMID- 16081812
TI  - Immature CD4- CD103+ rat dendritic cells induce rapid caspase-independent
      apoptosis-like cell death in various tumor and nontumor cells and phagocytose
      their victims.
AB  - We previously reported the characterization of a MHC class II(low) CD4- CD103+
      (CD4-) subset of dendritic cells (DC) in rat spleen that exhibit a Ca2+-, Fas
      ligand-, TRAIL- and TNF-alpha-independent cytotoxic activity against specific
      targets in vitro. In this study, we demonstrate that this DC subset was also
      found in lymph nodes. Freshly extracted and, therefore, immature CD4- DC
      exhibited a potent cytotoxic activity against a large panel of tumor cell lines
      as well as primary endothelial cells. The cytotoxic activity of immature CD4- DC
      required cell-to-cell contact and de novo protein expression. CD4- DC-mediated
      cell death resembled apoptosis, as evidenced by outer membrane phosphatidylserine
      exposure and nuclear fragmentation in target cells, but was caspase as well as
      Fas-associated death domain and receptor-interacting protein independent. Bcl-2
      overexpression in target cells did not protect them against DC-mediated cell
      death. Immature CD4- DC phagocytosed efficiently apoptotic cells in vitro and,
      therefore, rapidly and specifically engulfed their victims following death
      induction. Maturation induced a dramatic down-regulation of the killing and
      phagocytic activities of CD4- DC. In contrast, CD4+ DC were both unable to kill
      target cells and to phagocytose apoptotic cells in vitro. Taken together, these
      data indicate that rat immature CD4- CD103+ DC mediate an unusual cytotoxic
      activity and can use this function to efficiently acquire Ag from live cells.

PMID- 16081813
TI  - Demonstration of autoimmunity in the tight skin-2 mouse: a model for scleroderma.
AB  - The tight skin-2 (Tsk2/+) mouse has been proposed as an animal model of systemic
      sclerosis (SSc) because this animal exhibits increased collagen synthesis and
      accumulation in the dermis. The Tsk2/+ mouse also has been reported to have a
      mononuclear cell infiltrate in the dermis; however, to date no evidence of
      autoimmunity has been described in this animal model. We report here that Tsk2/+
      mice harbor numerous autoantibodies in their plasma including some, which are
      similar to those, present in SSc patients. Immunofluorescence with HEp-2 cells
      revealed the presence of anti-nuclear Abs (ANAs) in the plasma of 92% of the
      Tsk2/+ mice. In contrast, <5% of cage-mated CAST/ei mice had a positive ANA and
      none of the C3H/HeJ age-matched controls were positive. Homogenous, speckled,
      rim, nucleolar, centromere as well as combinations of these patterns were
      observed. The proportion of Tsk2/+ animals with a positive ANA increased slightly
      with age. ELISAs showed that 93% of the Tsk2/+ animals were positive for anti
      Scl70, 82% for anti-centromere, 5% for anti-RNP/Sm, and none were positive for
      anti-RNA-polymerase II Abs. Indirect immunofluorescence with Crithidia luciliae
      and ELISA for anti-dsDNA Abs showed that 76% of Tsk2/+ mice were positive for
      this autoantibody. The high frequency of anti-Scl70 and anti-centromere
      autoantibodies indicates that Tsk2/+ mice display some humoral immune alterations
      which are similar to those found in patients with SSc. However, the Tsk2/+ mice
      also develop autoantibodies to dsDNA and a majority of the mice develop multiple
      autoantibody specificities (anti-Scl70, anti-CENP-B, and anti-dsDNA) indicating
      that the mouse may be a useful model to study autoimmunity in a wider spectrum of
      connective tissue diseases.

PMID- 16081814
TI  - Characterization of a C3a receptor in rainbow trout and Xenopus: the first
      identification of C3a receptors in nonmammalian species.
AB  - Virtually nothing is known about the structure, function, and evolutionary
      origins of the C3aR in nonmammalian species. Because C3aR and C5aR are thought to
      have arisen from the same common ancestor, the recent characterization of a C5aR
      in teleost fish implied the presence of a C3aR in this animal group. In this
      study we report the cloning of a trout cDNA encoding a 364-aa molecule (TC3aR)
      that shows a high degree of sequence homology and a strong phylogenetic
      relationship with mammalian C3aRs. Northern blotting demonstrated that TC3aR was
      expressed primarily in blood leukocytes. Flow cytometric analysis and
      immunofluorescence microscopy showed that Abs raised against TC3aR stained to a
      high degree all blood B lymphocytes and, to a lesser extent, all granulocytes.
      More importantly, these Abs inhibited trout C3a-mediated intracellular calcium
      mobilization in trout leukocytes. A fascinating structural feature of TC3aR is
      the lack of a significant portion of the second extracellular loop (ECL2). In all
      C3aR molecules characterized to date, the ECL2 is exceptionally large when
      compared with the same region of C5aR. However, the exact function of the extra
      portion of ECL2 is unknown. The lack of this segment in TC3aR suggests that the
      extra piece of ECL2 was not necessary for the interaction of the ancestral C3aR
      with its ligand. Our findings represent the first C3aR characterized in
      nonmammalian species and support the hypothesis that if C3aR and C5aR diverged
      from a common ancestor, this event occurred before the emergence of teleost fish.

PMID- 16081815
TI  - HLA-B27 misfolding in transgenic rats is associated with activation of the
      unfolded protein response.
AB  - The mechanism by which the MHC class I allele, HLA-B27, contributes to
      spondyloarthritis pathogenesis is unknown. In contrast to other alleles that have
      been examined, HLA-B27 has a tendency to form high m.w. disulfide-linked H chain
      complexes in the endoplasmic reticulum (ER), bind the ER chaperone BiP/Grp78, and
      undergo ER-associated degradation. These aberrant characteristics have provided
      biochemical evidence that HLA-B27 is prone to misfold. Recently, similar
      biochemical characteristics of HLA-B27 were reported in cells from HLA-B27/human
      beta2-microglobulin transgenic (HLA-B27 transgenic) rats, an animal model of
      spondyloarthritis, and correlated with disease susceptibility. In this study, we
      demonstrate that the unfolded protein response (UPR) is activated in macrophages
      derived from the bone marrow of HLA-B27 transgenic rats with inflammatory
      disease. Microarray analysis of these cells also reveals an IFN response
      signature. In contrast, macrophages derived from premorbid rats do not exhibit a
      strong UPR or evidence of IFN exposure. Activation of macrophages from premorbid
      HLA-B27 transgenic rats with IFN-gamma increases HLA-B27 expression and leads to
      UPR induction, while no UPR is seen in cells from nondisease-prone HLA-B7
      transgenic or wild-type (nontransgenic) animals. This is the first demonstration,
      to our knowledge, that HLA-B27 misfolding is associated with ER stress that
      results in activation of the UPR. These observations link HLA-B27 expression with
      biological effects that are independent of immunological recognition, but
      nevertheless may play an important role in the pathogenesis of inflammatory
      diseases associated with this MHC class I allele.

PMID- 16081816
TI  - Early phosphorylation kinetics of proteins involved in proximal TCR-mediated
      signaling pathways.
AB  - Activation of T cells via the stimulation of the TCR plays a central role in the
      adaptive immunological response. Although much is known about TCR-stimulated
      signaling pathways, there are still gaps in our knowledge about the kinetics and
      sequence of events during early activation and about the in vivo specificity of
      kinases involved in these proximal signaling pathways. This information is
      important not only for understanding the activation of signaling pathways
      important for T cell function but also for the development of drug targets and
      computer-based molecular models. In this study, phospho-specific Abs directed
      toward individual sites on signaling proteins were used to investigate the early
      phosphorylation kinetics of proteins involved in proximal TCR-induced pathways.
      These studies indicate that linker for activation of T cells' tyrosines have
      substantially different phosphorylation kinetics and that Src homology 2 domain
      containing leukocyte protein of 76 kDa has rapid, transient phosphorylation
      kinetics compared to other proteins. In additions, we provide evidence that ZAP
      70 is the primary in vivo kinase for LAT tyrosine 191 and that Itk plays a role
      in the phosphorylation of tyrosine 783 on phospholipase C-gamma1. In total, these
      studies give new insight into the sequence, kinetics and specificity of early TCR
      mediated signaling events that are vital for T cell activation.

PMID- 16081817
TI  - Structures of three HIV-1 HLA-B*5703-peptide complexes and identification of
      related HLAs potentially associated with long-term nonprogression.
AB  - Long-term nonprogression during acute HIV infection has been strongly associated
      with HLA-B*5701 or HLA-B*5703. In this study, we present the high resolution
      crystal structures of HLA-B*5703 complexes with three HIV-1 epitopes: ISPRTLNAW
      (ISP), KAFSPEVIPMF (KAF-11), and KAFSPEVI (KAF-8). These reveal peptide anchoring
      at position 2 and their C termini. The different peptide lengths and primary
      sequences are accommodated by variation in the specific contacts made to the HLA
      B*5703, flexibility in water structure, and conformational adjustment of side
      chains within the peptide-binding groove. The peptides adopt markedly different
      conformations, and trap variable numbers of water molecules, near a cluster of
      tyrosine side chains located in the central region of the peptide-binding groove.
      The KAF-11 epitope completely encompasses the shorter KAF-8 epitope but the
      peptides are presented in different conformations; the KAF-11 peptide arches out
      of the peptide-binding groove, exposing a significant main chain surface area.
      Bioinformatic analysis of the MHC side chains observed to contribute to the
      peptide anchor specificity, and other specific peptide contacts, reveals HLA
      alleles associated with long-term nonprogression and a number of related HLA
      alleles that may share overlapping peptide repertoires with HLA-B*5703 and thus
      may display a similar capacity for efficient immune control of HIV-1 infection.

PMID- 16081818
TI  - Recombinant CD200 protein does not bind activating proteins closely related to
      CD200 receptor.
AB  - CD200 (OX2) is a cell surface glycoprotein that interacts with a structurally
      related receptor (CD200R) expressed mainly on myeloid cells and is involved in
      regulation of macrophage and mast cell function. In mouse there are up to five
      genes related to CD200R with conflicting data as to whether they bind CD200. We
      show that mouse CD200 binds the inhibitory receptor CD200R with a comparable
      affinity (Kd = 4 microM) to those found for the rat and human CD200 CD200R
      interactions. CD200 gave negligible binding to the activating receptors,
      CD200RLa, CD200RLb, and CD200RLc, by direct analysis at the protein level using
      recombinant monomeric and dimeric fusion proteins or to CD200RLa and CD200RLb
      when expressed at the cell surface. An additional potential activating gene,
      CD200RLe, found in only some mouse strains also did not bind CD200. Thus, the
      CD200 receptor family consists of both activatory and inhibitory members like
      several other paired ligand receptors, such as signal regulatory protein, killer
      cell Ig-like receptor/KAR, LY49, dendritic cell immunoreceptor/dendritic cell
      immunoactivating receptor, and paired Ig-like type 2 receptor. Although the
      ligand for the inhibitory product is a widely distributed host protein, the
      ligands of the activating forms remain to be identified, and one possibility is
      that they are pathogen components.

PMID- 16081819
TI  - Two major interacting chromosome loci control disease susceptibility in murine
      model of spondyloarthropathy.
AB  - Autoimmune spondylitis was induced in BALB/c mice and their MHC-matched (BALB/c x
      DBA/2)F1 and F2 hybrids by systemic immunization with cartilage/intervertebral
      disk proteoglycan (PG). As in human ankylosing spondylitis, the MHC was the major
      permissive genetic locus in murine PG-induced spondylitis (PGIS). Two major non
      MHC chromosome loci with highly significant linkage were found on chromosomes 2
      (Pgis2) and 18 (Pgis1) accounting for 40% of the entire F2 trait variance. The
      dominant spondylitis-susceptibility allele for Pgis2 locus is derived from the
      BALB/c strain, whereas the Pgis1 recessive allele was present in the disease
      resistant DBA/2 strain. The Pgis1 locus significantly affected the disease
      controlling Pgis2 locus, inducing as high incidence of spondylitis in F2 hybrids
      as was found in the spondylitis-susceptible parent BALB/c strain. Additional
      disease-controlling loci with suggestive linkage were mapped to the chromosomes
      12, 15, and 19. Severity of spondylitis in F2 mice positively correlated with
      serum levels of amyloid A, IL-6, and Pg-specific Abs, and showed negative
      correlation with Ag-induced T cell proliferation, IFN-gamma, IL-4, and TNF-alpha
      production. A major locus controlling serum IL-6 was found on chromosome 14 near
      osteoclast differentiation factor Tnfsf11. Locus on chromosome 11 near the Stat3
      and Stat5 genes controlled serum level of the Ig IgG2a isotype. The two major
      genetic loci Pgis1 and Pgis2 of murine spondylitis were homologous to chromosome
      regions in human genome, which control ankylosing spondylitis in human patients.
      Thus, this animal model of experimentally induced spondylitis might facilitate
      the identification of spondylitis-susceptibility genes in humans.

PMID- 16081820
TI  - Identification and bioactivities of IFN-gamma in rainbow trout Oncorhynchus
      mykiss: the first Th1-type cytokine characterized functionally in fish.
AB  - IFN-gamma is one of the key cytokines in defining Th1 immune responses. In this
      study, an IFN-gamma homologue has been identified in rainbow trout Oncorhynchus
      mykiss, and its biological activities have been characterized. The trout IFN
      gamma cDNA is 1034 bp in length and translates into a 180-aa protein. The first
      intron of the trout IFN-gamma gene contains highly polymorphic GACA
      minisatellites and 44-bp DNA repeats, giving rise to at least six alleles. IFN
      gamma is structurally conserved among vertebrates, and a signature motif has been
      identified. A nuclear localization sequence known to be crucial for IFN-gamma
      biological activities is also present in the C-terminal region of the trout IFN
      gamma. The IFN-gamma expression was induced in head kidney leukocytes by
      stimulation with PHA or poly(I:C) and in kidney and spleen of fish injected with
      poly(I:C). rIFN-gamma produced in Escherichia coli significantly stimulated gene
      expression of IFN-gamma-inducible protein 10 (gammaIP-10), MHC class II beta
      chain, and STAT1, and enhanced respiratory burst activity in macrophages.
      Deletion of 29-aa residues from the C terminus containing the nuclear
      localization sequence motif resulted in loss of activity with respect to
      induction of gammaIP-10 in RTS-11 cells. Moreover, IFN-gamma-induced gammaIP-10
      expression was completely abolished by the protein kinase C inhibitor
      staurosporine, and partially reduced by U0126, a specific inhibitor for ERKs.
      Taken together, the present study has demonstrated for the first time a
      functional IFN-gamma homologue in a fish species, strongly suggesting a conserved
      Th1 immune response is most likely present in lower vertebrates.

PMID- 16081821
TI  - Lymphoid differentiation pathways can be traced by TCR delta rearrangements.
AB  - TCR gene rearrangement generates diversity of T lymphocytes by V(D)J
      recombination. Ig genes are rearranged in B cells using the same enzyme
      machinery. TCRD (TCR delta) genes are frequently incompletely rearranged in B
      precursor leukemias and recently were found in a significant portion of
      physiological B lymphocytes. Incomplete TCRD rearrangements (V-D) thus serve as
      natural indicators of previous V(D)J recombinase activity. Functional V(D)J
      recombinase has recently been found in murine NK precursors. We tested whether
      physiological NK cells and other leukocyte subpopulations contained TCR
      rearrangements in humans. This would provide evidence that V(D)J recombinase was
      active in the ancestry cells and suggest common pathways among the positive cell
      types. TCRD were rearranged in 3.2-36% of NK cells but not in nonlymphoid
      leukocytes. The previously known phenomenon of TCRD transcription in NK cells is
      a possible mechanism that maintains the chromatin open at the TCRD locus. In
      comparison, TCRG rearrangements were frequent in T cells, low to negative in B
      and NK cells, and negative in nonlymphoid cells, suggesting a tighter control of
      TCRG. Levels of TCRD rearrangements were similar among the B lymphocyte subsets
      (B1-B2, naive-memory). In conclusion, human NK cells pass through a
      differentiation step with active V(D)J recombinase similar to T and B lymphocytes
      and unlike nonlymphoid leukocytes. This contradicts recent challenges to the
      concept of separate lymphoid and myeloid differentiation.

PMID- 16081822
TI  - The induction of a type 1 immune response following a Trypanosoma brucei
      infection is MyD88 dependent.
AB  - The initial host response toward the extracellular parasite Trypanosoma brucei is
      characterized by the early release of inflammatory mediators associated with a
      type 1 immune response. In this study, we show that this inflammatory response is
      dependent on activation of the innate immune system mediated by the adaptor
      molecule MyD88. In the present study, MyD88-deficient macrophages are
      nonresponsive toward both soluble variant-specific surface glycoprotein (VSG), as
      well as membrane-bound VSG purified from T. brucei. Infection of MyD88-deficient
      mice with either clonal or nonclonal stocks of T. brucei resulted in elevated
      levels of parasitemia. This was accompanied by reduced plasma IFN-gamma and TNF
      levels during the initial stage of infection, followed by moderately lower VSG
      specific IgG2a Ab titers during the chronic stages of infection. Analysis of
      several TLR-deficient mice revealed a partial requirement for TLR9 in the
      production of IFN-gamma and VSG-specific IgG2a Ab levels during T. brucei
      infections. These results implicate the mammalian TLR family and MyD88 signaling
      in the innate immune recognition of T. brucei.

PMID- 16081823
TI  - Plasmodium yoelii can ablate vaccine-induced long-term protection in mice.
AB  - Malaria is a serious cause of morbidity and mortality for people living in
      endemic areas, but unlike many other infections, individuals exposed to the
      parasite do not rapidly become resistant to subsequent infections. High titers of
      Ab against the 19-kDa C-terminal fragment of the merozoite surface protein-1 can
      mediate complete protection in model systems; however, previous studies had not
      determined whether this vaccine generated long-term protection. In this study, we
      report that functional memory cells generated by merozoite surface protein-1, per
      se, do not offer any protection. This is because the parasite induces deletion of
      vaccine-specific memory B cells as well as long-lived plasma cells including
      those specific for bystander immune responses. Our study demonstrates a novel
      mechanism by which Plasmodium ablates immunological memory of vaccines, which
      would leave the host immuno-compromised.

PMID- 16081824
TI  - IL-10 from regulatory T cells determines vaccine efficacy in murine Leishmania
      major infection.
AB  - Leishmaniasis affects 12 million people, but there are no vaccines. Immunological
      correlates of vaccine efficacy are unclear. Polarized Th1 vs Th2 responses in
      Leishmania major-infected mice suggested that a shift in balance from IL-4 to IFN
      gamma was the key to vaccine success. Recently, a role for IL-10 and regulatory T
      cells in parasite persistence was demonstrated, prompting re-evaluation of
      vaccine-induced immunity. We compared DNA/modified vaccinia virus Ankara
      heterologous prime-boost with Leishmania homolog of the receptor for activated C
      kinase (LACK) or tryparedoxin peroxidase (TRYP). Both induced low IL-4 and high
      IFN-gamma prechallenge. Strikingly, high prechallenge CD4 T cell-derived IL-10
      predicted vaccine failure using LACK, whereas low IL-10 predicted protection with
      TRYP. The ratio of IFN-gamma:IL-10 was thus a clear prechallenge indicator of
      vaccine success. Challenge infection caused further polarization to high IL
      10/low IFN-gamma with LACK and low IL-10/high IFN-gamma with TRYP. Ex vivo
      quantitative RT-PCR and in vitro depletion and suppression experiments
      demonstrated that Ag-driven CD4+ CD25+ T regulatory 1-like cells were the primary
      source of IL-10 in LACK-vaccinated mice. Anti-IL-10R treatment in vivo
      demonstrated that IL-10 was functional in determining vaccine failure, rendering
      LACK protective in the presence of high IFN-gamma/low IL-5 responses.

PMID- 16081825
TI  - Ligation of cell surface-associated glucose-regulated protein 78 by receptor
      recognized forms of alpha 2-macroglobulin: activation of p21-activated protein
      kinase-2-dependent signaling in murine peritoneal macrophages.
AB  - Previous studies of the plasma proteinase inhibitor alpha2-macroglobulin
      (alpha2M) demonstrated that alpha2M-proteinase complexes (alpha2M*) modulate
      immune responses and promotes macrophage locomotion and chemotaxis. Alpha2M*
      binds to cell surface-associated glucose-regulated protein 78 (GRP78), which
      activates downstream signaling events. The role of p21-activated protein kinase-1
      and -2 (PAK-1 and -2) in promoting cellular motility is well documented. In the
      current study, we examined the ability of alpha2M* to activate PAK-1 and PAK-2.
      Upon macrophage stimulation with alpha2M*, PAK-2 is autophosphorylated, resulting
      in increased kinase activity; however, PAK-1 is negligibly affected. Alpha2M*
      stimulated macrophages showed a marked elevation in the levels of Rac x GTP.
      Receptor tyrosine phosphorylation upon binding of alpha2M* to GRP78, recruits PAK
      2 to the plasma membrane via the adaptor protein NCK. Consistent with this
      hypothesis, silencing of GRP78 gene expression greatly attenuated the levels of
      membrane-associated PAK-2 and NCK. PAK-2 activity was markedly decreased by
      inhibition of tyrosine kinases and PI3K before alpha2M* stimulation. We further
      demonstrate that phosphorylation of Lin-11, Isl-1, Mec-3 (LIM) kinase and cofilin
      is promoted by treating macrophages with alpha2M*. Thus, alpha2M* regulates
      activation of the PAK-2-dependent motility mechanism in these cells.

PMID- 16081826
TI  - Heterozygous Arg753Gln polymorphism of human TLR-2 impairs immune activation by
      Borrelia burgdorferi and protects from late stage Lyme disease.
AB  - Lyme disease (LD) is caused by Borrelia burgdorferi and displays different
      stages, including localized, early disseminated, and persistent infection, all of
      which are associated with profound inflammatory reactions in the host. Induction
      of proinflammatory cytokines by B. burgdorferi is mainly mediated by outer
      surface proteins interacting with TLR-2/TLR-1 heterodimers. In this study, we
      show that TNF-alpha induction by Borrelia lysate was impaired in heterozygous TLR
      2 knockout mice, while reactivity to lipoteichoic acid, another TLR-2 ligand
      signaling via TLR-2/TLR-6 heterodimers, was unaffected. Blood from individuals
      heterozygous for the TLR-2 polymorphism Arg753Gln was tested for cytokine release
      upon stimulation with Borrelia lysate, and induction of TNF-alpha and IFN-gamma
      was significantly lower as compared with individuals not exhibiting this
      variation. Overexpression of TLR-2 carrying the Arg753Gln polymorphism in HEK 293
      cells led to a significantly stronger impairment of activation by TLR-2/TLR-1
      ligands as compared with TLR-2/TLR-6 ligands. To study whether heterozygosity for
      the Arg753Gln variant of TLR-2 influenced susceptibility for LD, we analyzed 155
      patients for this polymorphism. The Arg753Gln variant occurs at a significantly
      lower frequency in LD patients as compared with matched controls (5.8 vs 13.5%,
      odds ratio 0.393, 95% confidence interval 0.17-0.89, p = 0.033), with an even
      more pronounced difference when late stage disease was observed (2.3 vs 12.5%,
      odds ratio 0.163, 95% confidence interval 0.04-0.76, p = 0.018). These data
      suggest that Arg753Gln may protect from the development of late stage LD due to a
      reduced signaling via TLR-2/TLR-1.

PMID- 16081827
TI  - Ag85B of mycobacteria elicits effective CTL responses through activation of
      robust Th1 immunity as a novel adjuvant in DNA vaccine.
AB  - CD4+ T cells play a crucial role in CTL generation in a DNA vaccination strategy.
      Several studies have demonstrated the requirement of CD4+ T cells for the
      induction of a sufficient immune response by coadministrating DNAs. In the
      present study we investigated the effectiveness of Ag85B of mycobacteria, which
      is known to be one of the immunogenic proteins for Th1 development, as an
      adjuvant of a DNA vaccine. HIV gp120 DNA vaccine mixed with Ag85B DNA as an
      adjuvant induced HIV gp120-specific Th1 responses, as shown by delayed-type
      hypersensitivity, cytokine secretion, and increasing HIV-specific CTL responses.
      Moreover, these responses were enhanced in mice primed with Mycobacterium bovis
      bacillus Calmette-Guerin before immunization of HIV DNA vaccine mixed with Ag85B
      DNA. Furthermore, these immunized mice showed substantial reduction of HIV gp120
      expressing recombinant vaccinia virus titers compared with the titers in other
      experimental mice after recombinant vaccinia virus challenge. Because most humans
      have been sensitized by spontaneous infection or by vaccination with
      mycobacteria, these findings indicate that Ag85B is a promising adjuvant for
      enhancing CTL responses in a DNA vaccination strategy.

PMID- 16081828
TI  - A soluble factor secreted by an HIV-1-resistant cell line blocks transcription
      through inactivating the DNA-binding capacity of the NF-kappa B p65/p50 dimer.
AB  - The identity and activity of several anti-HIV soluble factor(s) secreted by CD8
      and CD4 T lymphocytes have been determined; however, some of them still await
      definition. We have established an HIV-1-resistant, transformed CD4 T cell line
      that secretes HIV-1 resistance protein(s). Our studies indicate that this
      protein(s), called HIV-1 resistance factor (HRF), inhibits transcription of the
      virus by interfering with the activity of NF-kappaB. In the present report we
      identified the site at which HRF exerts this inhibition by evaluating a set of
      discrete events in NF-kappaB action. We tested the kappaB oligonucleotide binding
      activity in nuclei of resistant cells, nuclear translocation and binding to the
      HIV-1 long terminal repeat of p65 and p50 proteins from susceptible cells after
      exposure to HRF, and the binding of recombinant p50 to the kappaB oligonucleotide
      in vitro as affected by prior or simultaneous exposure to HRF. The results of
      this experimental schema indicate that HRF interacts with p50 after it enters the
      nucleus, but before its binding to DNA and that this interaction impedes the
      formation of an NF-kappaB-DNA complex required for the promotion of
      transcription. These findings suggest that HRF mediates a novel innate immune
      response to virus infection.

PMID- 16081829
TI  - Mechanisms of group B streptococcal-induced apoptosis of murine macrophages.
AB  - Apoptosis of murine and human macrophages induced by group B Streptococcus
      agalactiae (GBS) is likely an important virulence mechanism that is used by the
      bacteria to suppress the host immune response and to persist at sites of
      infection. The mechanisms by which GBS induces apoptosis are, however, largely
      unknown. In this study, we report that in murine macrophages GBS induces unique
      changes in the regulation and localization of the apoptotic regulators Bad, 14-3
      3, and Omi/high-temperature requirement A2 and leads to the release of cytochrome
      c and the activation of caspase-9 and caspase-3. Furthermore, inhibition of
      caspase-3 impaired GBS-induced apoptosis of macrophages. The ability to modulate
      the activity of effector caspases may therefore represent an unexploited avenue
      for therapeutic intervention in GBS infections.

PMID- 16081830
TI  - Immune regulation of protease-activated receptor-1 expression in murine small
      intestine during Nippostrongylus brasiliensis infection.
AB  - Infection with gastrointestinal nematodes exerts profound effects on both immune
      and physiological responses of the host. Helminth infection induces a
      hypercontractility of intestinal smooth muscle that is dependent on the Th2
      cytokines, IL-4 and IL-13, and may contribute to worm expulsion. Protease
      activated receptors (PARs) are expressed throughout the gut, and activation of
      PAR-1 was observed in asthma, a Th2-driven pathology. In the current study we
      investigated the physiologic and immunologic regulation of PAR-1 in the murine
      small intestine, specifically 1) the effect of PAR-1 agonists on small intestinal
      smooth muscle contractility, 2) the effects of Nippostrongylus brasiliensis
      infection on PAR-1 responses, 3) the roles of IL-13 and IL-4 in N. brasiliensis
      infection-induced alterations in PAR-1 responses, and 4) the STAT6 dependence of
      these responses. We demonstrate that PAR-1 activation induces contraction of
      murine intestinal smooth muscle that is enhanced during helminth infection. This
      hypercontractility is associated with an elevated expression of PAR-1 mRNA and
      protein. N. brasiliensis-induced changes in PAR-1 function and expression were
      seen in IL-4-deficient mice, but not in IL-13- or STAT6-deficient mice,
      indicating the dependence of IL-13 on the STAT6 signaling pathway independent of
      IL-4.

PMID- 16081831
TI  - Identification of high and low responders to lipopolysaccharide in normal
      subjects: an unbiased approach to identify modulators of innate immunity.
AB  - LPS stimulates a vigorous inflammatory response from circulating leukocytes that
      varies greatly from individual to individual. The goal of this study was to use
      an unbiased approach to identify differences in gene expression that may account
      for the high degree of interindividual variability in inflammatory responses to
      LPS in the normal human population. We measured LPS-induced cytokine production
      ex vivo in whole blood from 102 healthy human subjects and identified individuals
      who consistently showed either very high or very low responses to LPS (denoted
      lps(high) and lps(low), respectively). Comparison of gene expression profiles
      between the lps(high) and lps(low) individuals revealed 80 genes that were
      differentially expressed in the presence of LPS and 21 genes that were
      differentially expressed in the absence of LPS (p < 0.005, ANOVA). Expression of
      a subset of these genes was confirmed using real-time RT-PCR. Functional
      relevance for one gene confirmed to be expressed at a higher level in lps(high),
      adipophilin, was inferred when reduction in adipophilin mRNA by small interfering
      RNA in the human monocyte-like cell line THP-1 resulted in a modest but
      significant reduction in LPS-induced MCP-1 mRNA expression. These data illustrate
      a novel approach to the identification of factors that determine interindividual
      variability in innate immune inflammatory responses and identify adipophilin as a
      novel potential regulator of LPS-induced MCP-1 production in human monocytes.

PMID- 16081832
TI  - Interaction between synovial inflammatory tissue and bone marrow in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) leads to destruction of cartilage and bone. Whether
      rheumatoid arthritis also affects the adjacent bone marrow is less clear. In this
      study, we investigated subcortical bone marrow changes in joints from patients
      with RA. We describe penetration of the cortical barrier by synovial inflammatory
      tissue, invasion into the bone marrow cavity and formation of mononuclear cell
      aggregates with B cells as the predominant cell phenotype. B cells expressed
      common B cell markers, such as CD20, CD45RA, and CD79a, and were mature B cells,
      as indicated by CD27 expression. Plasma cells were also present and were enriched
      in the regions between aggregates and inflammatory tissue. Moreover, molecules
      for B cell chemoattraction, such as BCA-1 and CCL-21, homing, mucosal addressin
      cell adhesion molecule-1 and survival, BAFF, were expressed. Endosteal bone next
      to subcortical bone marrow aggregates showed an accumulation of osteoblasts and
      osteoid deposition. In summary, we show that synovial inflammatory tissue can
      reach the adjacent bone marrow by fully breaking the cortical barrier, which
      results in formation of B cell-rich aggregates as well as increased formation of
      new bone. This suggests that bone marrow is an additional compartment in the
      disease process of RA.

PMID- 16081833
TI  - Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced
      airway inflammation.
AB  - Matrix metalloproteinases (MMPs) are involved in inflammatory reaction, including
      asthma-related airway inflammation. MMP-8, mainly produced by neutrophils, has
      recently been reported to be increased in the bronchoalveolar lavage fluid (BALF)
      from asthmatic patients. To evaluate the role of MMP-8 in asthma, we measured MMP
      8 expression in lung tissue in an OVA-sensitized mouse model of asthma and
      addressed the effect of MMP-8 deletion on allergen-induced bronchial
      inflammation. MMP-8 production was increased in lungs from C57BL/6 mice exposed
      to allergens. After allergen exposure, MMP-8(-/-) mice developed an airway
      inflammation characterized by an increased neutrophilic inflammation in BALF and
      an increased neutrophilic and eosinophilic infiltration in the airway walls. MMP
      8 deficiency was associated with increased levels of IL-4 and anti-OVA IgE and
      IgG1 in BALF and serum, respectively. Although allergen exposure induced an
      enhancement of LPS-induced CXC chemokine, KC, and MIP-2 levels in BALF and lung
      parenchyma, no difference was observed between the two genotypes. Inflammatory
      cell apoptosis was reduced in the lungs from MMP-8(-/-) mice. For the first time,
      our study evidences an important role of MMP-8 in the control of neutrophilic and
      eosinophilic infiltration during allergen-induced lung inflammation, and
      demonstrates that the anti-inflammatory effect of MMP-8 is partly due to a
      regulation of inflammatory cell apoptosis.

PMID- 16081834
TI  - Protease-activated receptor-2 activation induces acute lung inflammation by
      neuropeptide-dependent mechanisms.
AB  - Protease-activated receptors (PARs) and tachykinin-immunoreactive fibers are
      located in the lung as sentries to respond to a variety of pathological stimuli.
      The effects of PAR activation on the lung have not been adequately studied. We
      report on the effects of instilling PAR-activating peptides (PAR-APs, including
      PAR1-, PAR2-, and PAR4-AP) into the lungs of ventilated or spontaneously
      breathing mice. PAR2-AP, but not PAR1-AP or PAR4-AP, caused a sharp increase in
      lung endothelial and epithelial permeability to protein, extravascular lung
      water, and airway tone. No responses to PAR2-AP were detected in PAR2 knockout
      mice. In bronchoalveolar lavage, PAR2 activation caused 8- and 5-fold increase in
      MIP-2 and substance P levels, respectively, and a 12-fold increase in the number
      of neutrophils. Ablation of sensory neurons (by capsaicin) markedly decreased the
      PAR2-mediated airway constriction, and virtually abolished PAR2-mediated
      pulmonary inflammation and edema, as did blockade of NK1 or NK2 receptors. Thus,
      PAR2 activation in the lung induces airway constriction, lung inflammation, and
      protein-rich pulmonary edema. These effects were either partly or completely
      neuropeptide dependent, suggesting that PAR2 can cause lung inflammation by a
      neurogenic mechanism.

PMID- 16081835
TI  - Prostaglandin E2 stimulates granulocyte colony-stimulating factor production via
      the prostanoid EP2 receptor in mouse peritoneal neutrophils.
AB  - G-CSF is a hemopoietic growth factor involved in granulocytic differentiation of
      progenitor cells. In this study, we investigated the effects of PGE2 on G-CSF
      production in murine peritoneal neutrophils in vitro and in vivo. PGE2 augmented
      LPS-primed G-CSF release from peritoneal neutrophils. This augmentation was
      mimicked by a type E prostanoid receptor (EP)2-selective agonist but not by other
      EP-specific agonists. Indeed, the effect of PGE2 on G-CSF release was abolished
      in neutrophils isolated from EP2-deficient mice. PGE2 and an EP2 agonist have the
      ability to stimulate G-CSF gene expression even in the absence of LPS. In the
      casein-induced peritonitis model, the appearance of G-CSF in the casein-injected
      peritoneal cavity associated well with the timing of neutrophil infiltration as
      well as PGE2 levels in exudates, with a peak value at 6 h postinjection.
      Inhibition of endogenous PG synthesis by indomethacin resulted in a marked
      decrease in G-CSF content and neutrophil number in the peritoneal cavity.
      Moreover, EP2-deficient mice exhibited a strikingly reduced G-CSF content in
      peritoneal exudates with comparable responses in neutrophil migration and local
      PGE2 production at 6 h postinjection. These results suggest that the PGE2-EP2
      system contributes to the local production of G-CSF during acute inflammation.

PMID- 16081836
TI  - Human airway smooth muscle cells express the high affinity receptor for IgE (Fc
      epsilon RI): a critical role of Fc epsilon RI in human airway smooth muscle cell
      function.
AB  - Several reports suggest that activated airway smooth muscle (ASM) cells are
      capable of generating various proinflammatory mediators, including cytokines and
      chemokines. However, little is known about the mechanism involved in this
      process. In this regard, we have examined the expression and the role of the high
      affinity IgE receptor (Fc epsilonRI) by ASM cells. Human ASM cells were found to
      constitutively express transcripts coding for alpha, beta, and gamma subunits of
      Fc epsilonRI. Flow cytometry and Western blot analysis confirmed the expression
      of Fc epsilonRI alpha-chain protein. Interestingly, Fc epsilonRI alpha-chain
      immunoreactivity was also demonstrated in smooth muscle within bronchial biopsies
      of asthmatic subjects. Cross-linking of Fc epsilonRI induced mobilization of free
      calcium in ASM cells, one of the critical signals to trigger smooth muscle
      contraction. Furthermore, cultured ASM cells released IL-4, IL-13, IL-5, and
      eotaxin but not IFN-gamma, when sensitized with IgE followed by anti-IgE Ab cross
      linking. The addition of anti-Fc epsilonRI alpha-chain Abs directed against IgE
      binding site inhibited this release. Taken together, these results suggest a
      potential new and important mechanism by which ASM cells may participate in
      airway inflammation and bronchoconstriction associated with allergic asthma.

PMID- 16081837
TI  - Heat shock protein-70 mediates the cytoprotective effect of carbon monoxide:
      involvement of p38 beta MAPK and heat shock factor-1.
AB  - Carbon monoxide (CO), a product of heme oxygenase activity, exerts antiapoptotic
      and anti-inflammatory effects in vitro and in vivo. The anti-inflammatory effects
      of CO involve the inhibition of TNF-alpha expression and the enhancement of IL-10
      production, resulting in reduced mortality after endotoxin challenge. In this
      study we demonstrate for the first time that the protective effects of CO involve
      the increased expression of the 70-kDa inducible heat shock protein (Hsp70) in
      murine lung endothelial cells and fibroblasts. The p38beta MAPK mediated the
      effects of CO on cytoprotection and Hsp70 regulation. Suppression of Hsp70
      expression and/or genetic deletion of heat shock factor-1, the principle
      transcriptional regulator of Hsp70, attenuated the cytoprotective and
      immunomodulatory effects of CO in mouse lung cells and in vivo. These data
      provide a novel mechanism for the protective effects of CO and underscore a
      potential application of this gaseous molecule in anti-inflammatory therapies.

PMID- 16081838
TI  - IL-converting enzyme/caspase-1 inhibitor VX-765 blocks the hypersensitive
      response to an inflammatory stimulus in monocytes from familial cold
      autoinflammatory syndrome patients.
AB  - Familial cold autoinflammatory syndrome (FCAS) and the related autoinflammatory
      disorders, Muckle-Wells syndrome and neonatal onset multisystem inflammatory
      disease, are characterized by mutations in the CIAS1 gene that encodes cryopyrin,
      an adaptor protein involved in activation of IL-converting enzyme/caspase-1.
      Mutations in cryopyrin are hypothesized to result in abnormal secretion of
      caspase-1-dependent proinflammatory cytokines, IL-1beta and IL-18. In this study,
      we examined cytokine secretion in PBMCs from FCAS patients and found a marked
      hyperresponsiveness of both IL-1beta and IL-18 secretion to LPS stimulation, but
      no evidence of increased basal secretion of these cytokines, or alterations in
      basal or stimulated pro-IL-1beta levels. VX-765, an orally active IL-converting
      enzyme/caspase-1 inhibitor, blocked IL-1beta secretion with equal potency in LPS
      stimulated cells from FCAS and control subjects. These results further link
      mutations in cryopyrin with abnormal caspase-1 activation, and support the
      clinical testing of caspase-1 inhibitors such as VX-765 in autoinflammatory
      disorders.

PMID- 16081839
TI  - Cytokine production by skin-derived mast cells: endogenous proteases are
      responsible for degradation of cytokines.
AB  - The current study characterizes the cytokine protein (ELISA) and mRNA (gene array
      and RT-PCR) profiles of skin-derived mast cells cultured under serum-free
      conditions when activated by cross-linking of Fc epsilonRI. Prior to mast cell
      activation, mRNA only for TNF-alpha was detected, while after activation mRNA for
      IL-5, IL-6, IL-13, TNF-alpha, and GM-CSF substantially increased, and for IL-4 it
      minimally increased. However, at the protein level certain recombinant cytokines,
      as measured by ELISAs, were degraded by proteases released by these skin-derived
      mast cells. IL-6 and IL-13 were most susceptible, followed by IL-5 and TNF-alpha;
      GM-CSF was completely resistant. These observations also held for the endogenous
      cytokines produced by activated mast cells. By using protease inhibitors, chymase
      and cathepsin G, not tryptase, were identified in the mast cell releasates as the
      likely culprits that digest these cytokines. Their cytokine-degrading
      capabilities were confirmed with purified chymase and cathepsin G. Soy bean
      trypsin inhibitor, when added to mast cell releasates, prevented the degradation
      of exogenously added cytokines and, when added to mast cells prior to their
      activation, prevented degradation of susceptible endogenous cytokines without
      affecting either degranulation or GM-CSF production. Consequently, substantial
      levels of IL-5, IL-6, IL-13, TNF-alpha, and GM-CSF were detected 24-48 h after
      mast cells had been activated, while none were detected 15 min after activation,
      by which time preformed granule mediators had been released. IL-4 was not
      detected at any time point. Thus, unless cytokines are protected from degradation
      by endogenous proteases, cytokine production by human mast cells with chymase and
      cathepsin G cells may be grossly underestimated.

PMID- 16081840
TI  - Mechanisms of peripheral tolerance following intracameral inoculation are
      independent of IL-13 or STAT6.
AB  - The peripheral tolerance that is elicited by the anterior chamber-associated
      immune deviation (ACAID) protocol is characterized by impairment of Th1 responses
      such as delayed-type hypersensitivity. It has been proposed that suppression of
      Th1 responses is mediated by a deviation toward Th2 responses. Because NKT cells
      have a prominent role in ACAID and NKT cell-derived IL-13 is required in a tumor
      model of tolerance, we postulated that NKT cell-derived Th2 cytokines might have
      a role in ACAID. However, contrary to the tumor model, in this study we show that
      NKT cells from IL-13-deficient mice or IL-4/IL-13 double deficient mice were able
      to reconstitute the capability of J alpha18-deficient mice (lacking invariant
      NKT) to develop peripheral tolerance postintracameral inoculation of Ag. Also, we
      were able to induce peripheral tolerance directly in IL-13-deficient, IL-4/IL-13
      double deficient, and STAT6-deficient mice by inoculation of Ag into their eye.
      We conclude that neither IL-4 nor IL-13 cytokines are required for the generation
      of efferent CD8+ T regulatory cells during eye-induced peripheral tolerance. We
      propose that Ags inoculated into the anterior chamber of the eye induce the
      immunoresponse to deviate from producing immune T effector cells to producing
      efferent T regulatory cells, rather than deviating from Th1- to Th2-type effector
      cells.

PMID- 16081841
TI  - Mobilization of human lymphoid progenitors after treatment with granulocyte
      colony-stimulating factor.
AB  - Hemopoietic stem and progenitor cells ordinarily residing within bone marrow are
      released into the circulation following G-CSF administration. Such mobilization
      has a great clinical impact on hemopoietic stem cell transplantation. Underlying
      mechanisms are incompletely understood, but may involve G-CSF-induced modulation
      of chemokines, adhesion molecules, and proteolytic enzymes. We studied G-CSF
      induced mobilization of CD34+ CD10+ CD19- Lin- and CD34+ CD10+ CD19+ Lin- cells
      (early B and pro-B cells, respectively). These mobilized lymphoid populations
      could differentiate only into B/NK cells or B cells equivalent to their marrow
      counterparts. Mobilized lymphoid progenitors expressed lymphoid- but not myeloid
      related genes including the G-CSF receptor gene, and displayed the same pattern
      of Ig rearrangement status as their bone marrow counterparts. Decreased
      expression of VLA-4 and CXCR-4 on mobilized lymphoid progenitors as well as
      multipotent and myeloid progenitors indicated lineage-independent involvement of
      these molecules in G-CSF-induced mobilization. The results suggest that by acting
      through multiple trans-acting signals, G-CSF can mobilize not only myeloid
      committed populations but a variety of resident marrow cell populations including
      lymphoid progenitors.

PMID- 16081842
TI  - Morphine withdrawal contributes to Th cell differentiation by biasing cells
      toward the Th2 lineage.
AB  - The consequences that drug withdrawal has on immune functioning has only recently
      been appreciated; however, given the wide variety of use and abuse of opiate
      analgesics, understanding the decrements to immune function that withdrawal from
      these drugs causes is of crucial importance. In previous work, we have
      demonstrated that morphine treatment contributes to immunosuppression by
      polarizing Th cells toward the Th2 lineage. In the current study, it was
      hypothesized that morphine withdrawal would result in Th2 differentiation and
      subsequent immune dysfunction. To address this hypothesis, mice were chronically
      treated with morphine for 72 h followed by a 24-h withdrawal period. It was
      determined that 24-h morphine withdrawal resulted in a decrease in IFN-gamma, the
      Th1 signature cytokine, whereas the Th2 cytokine, IL-4, was increased. In
      addition, Western blot and EMSA experiments revealed that morphine withdrawal
      induced Th2 differentiation was mediated through the classical Th2 transcription
      factors Stat-6 and GATA-3. In addition, the consequence of morphine withdrawal in
      the presence of an immune stimulation was also examined by treating mice in vivo
      with LPS before morphine withdrawal. Following withdrawal, it was found that the
      Th1-polarizing cytokine IL-12 was significantly decreased, providing further
      support for the observation that withdrawal results in Th2 differentiation by
      possibly impacting the generation of an appropriate innate immune response which
      directs subsequent adaptive Th1/Th2 responses.

PMID- 16081843
TI  - The selective estrogen receptor modulators, tamoxifen and raloxifene, impair
      dendritic cell differentiation and activation.
AB  - Most immune cells, including myeloid progenitors and terminally differentiated
      dendritic cells (DC), express estrogen receptors (ER) making these cells
      sensitive to estrogens. Our laboratory recently demonstrated that 17-beta
      estradiol (E2) promotes the GM-CSF-mediated development of CD11c+ CD11b(int) DC
      from murine bone marrow precursors. We tested whether the therapeutic selective
      estrogen receptor modulators (SERM), raloxifene and tamoxifen, can perturb DC
      development and activation. SERM, used in treatment of breast cancer and
      osteoporosis, bind to ER and mediate tissue-specific agonistic or antagonistic
      effects. Raloxifene and tamoxifen inhibited the differentiation of estrogen
      dependent DC from bone marrow precursors ex vivo in competition experiments with
      physiological levels of E2. DC differentiated in the presence of SERM were
      assessed for their capacity to internalize fluoresceinated Ags as well as respond
      to inflammatory stimuli by increasing surface expression of molecules important
      for APC function. Although SERM-exposed DC exhibited increased ability to
      internalize Ags, they were hyporesponsive to bacterial LPS: relative to control
      DC, they less efficiently up-regulated the expression of MHC class II, CD86, and
      to a lesser extent, CD80 and CD40. This phenotype indicates that these SERM act
      to maintain DC in an immature state by inhibiting DC responsiveness to
      inflammatory stimuli. Thus, raloxifene and tamoxifen impair E2-promoted DC
      differentiation and reduce the immunostimulatory capacity of DC. These
      observations suggest that SERM may depress immunity when given to healthy
      individuals for the prevention of osteoporosis and breast cancer and may
      interfere with immunotherapeutic strategies to improve antitumor immunity in
      breast cancer patients.

PMID- 16081844
TI  - Altered cytokine responses of dengue-specific CD4+ T cells to heterologous
      serotypes.
AB  - The interplay of different inflammatory cytokines induced during a dengue (DEN)
      virus infection plays a role in either protection or increased disease severity.
      We measured the frequencies and characterized the cytokine responses of DEN virus
      specific memory CD4+ T cells in PBMC of six volunteers who received experimental
      live attenuated monovalent DEN vaccines. IFN-gamma and TNF-alpha responses to
      inactivated DEN Ags were detected in up to 0.54 and 1.17% of total circulating
      CD4+ T cells, respectively. Ags from the homologous serotype elicited the highest
      IFN-gamma response. The ratio of TNF-alpha- to IFN-gamma-producing CD4+ T cells
      was higher after stimulation with Ags from heterologous DEN serotypes. Peptide
      specific CD4+ T cell frequencies of up to 0.089% were detected by direct staining
      using HLA class II tetramers. IFN-gamma and TNF-alpha responses to individual HLA
      class II-restricted peptide epitopes were detected in up to 0.05 and 0.27% of
      CD4+ T cells, respectively. Peptide sequences from the homologous serotype
      elicited a variety of cytokine response patterns. TNF-alpha- to IFN-gamma
      positive CD4+ T cell ratios varied between peptides, but the ratio of the sum of
      responses was highest against heterologous serotypes. These results demonstrate
      epitope sequence-specific differences in T cell effector function. These patterns
      of effector responses may play a role in the immunopathogenesis of DEN
      hemorrhagic fever.

PMID- 16081845
TI  - Cigarette smoke extract suppresses human dendritic cell function leading to
      preferential induction of Th-2 priming.
AB  - Dendritic cells (DC) are key regulators of immune responses. In the current
      study, we hypothesized that cigarette smoke-induced aberrance in DC function is
      an important mechanism by which smokers develop cancer, infection, and allergy-
      diseases common in smokers. We demonstrate that cigarette smoke extract (CSE)
      inhibits DC-mediated priming of T cells, specifically inhibiting the secretion of
      IFN-gamma whereas enhancing the production of IL-4 in the MLR. Conditioning with
      CSE did not effect cytokine (IL-10, IL-6, or IL-12) production from immature DCs,
      but significantly inhibited IL-12p70 release by LPS-matured DCs. In contrast, IL
      10 secretion by LPS-activated CSE-conditioned DCs was enhanced when compared with
      control DCs. CSE also induced cyclooxygenase-2 protein levels in maturing DCs and
      significantly augmented endogenous PGE2 release. Conditioning of DCs with CSE
      also suppressed LPS-mediated induction of CD40, CD80, and CD86, and suppressed
      maturation-associated CCR7 expression. Although CSE has been reported to induce
      apoptosis of fibroblasts and epithelial cells, the immunomodulatory effects
      observed with CSE were not due to diminished DC viability. The effects of CSE on
      DC function were not exclusively mediated by nicotine, because equivalent, or
      even higher concentrations of nicotine than those found in CSE, failed to
      suppress DC-induced T cell priming. These data provide evidence that soluble
      components extracted from cigarette smoke suppress key DC functions and favor the
      development of Th-2 immunity.

PMID- 16081846
TI  - Nuclear autoantigen translocation and autoantibody opsonization lead to increased
      dendritic cell phagocytosis and presentation of nuclear antigens: a novel
      pathogenic pathway for autoimmunity?
AB  - Autoreactivity in lupus requires the delivery of autoantigens to APCs in a
      proinflammatory context. It has been proposed that apoptotic cells are a source
      of lupus autoantigens and targets for autoantibodies. Using a histone H2B-GFP
      fusion protein as traceable Ag, we show here that lupus autoantibodies, directed
      against nuclear autoantigens, can opsonize apoptotic cells, enhance their uptake
      through induction of proinflammatory Fc gammaR-mediated phagocytosis, and augment
      Ag-specific T cell proliferation by increasing Ag loading. Apoptotic blebs and
      bodies seemed to be a preferred target of DC phagocytosis, via both "eat-me
      signals" and Fc gammaR-mediated mechanisms; furthermore, inhibition of nuclear Ag
      redistribution, by blockade of chromatin fragmentation, could stop binding and
      opsonization of apoptotic cells by autoantibodies, and inhibited Fc gamma-R
      mediated enhancement of phagocytosis. Our results suggest that DC uptake of
      opsonized histones and other nuclear Ags from apoptotic cells is a novel pathway
      for the presentation of nuclear Ags in a highly inflammatory context. Blockade of
      chromatin fragmentation in lupus is a potential therapeutic approach, which could
      theoretically limit DC access to autoantigens delivered in proinflammatory
      context, while leaving available for tolerization those delivered in a
      noninflammatory context.

PMID- 16081847
TI  - CCR3 expression and function in asthmatic airway smooth muscle cells.
AB  - Asthma is characterized by an increase in airway smooth muscle mass and a
      decreased distance between the smooth muscle layer and the epithelium.
      Furthermore, there is evidence to indicate that airway smooth muscle cells (ASMC)
      express a wide variety of receptors involved in the immune response. The aims of
      this study were to examine the expression of CCR3 on ASMC, to compare this
      expression between asthmatic and nonasthmatic subjects, and to determine the
      implications of CCR3 expression in the migration of ASMC. We first demonstrated
      that ASMC constitutively express CCR3 at both mRNA and protein levels.
      Interestingly, TNF-alpha increases ASMC surface expression of CCR3 from 33 to
      74%. Furthermore, using FACS analysis, we found that ASMC CCR3 is expressed to a
      greater degree in asthmatic vs control subjects (95 vs 75%). Functionality of the
      receptor was demonstrated by calcium assay; the addition of CCR3 ligand eotaxin
      to ASMC resulted in an increase in intracellular calcium production.
      Interestingly, ASMC was seen to demonstrate a positive chemotactic response to
      eotaxin. Indeed, ASMC significantly migrated toward 100 ng/ml eotaxin (2.2-fold
      increase, compared with control). In conclusion, the expression of CCR3 by ASMC
      is increased in asthmatics, and our data show that a CCR3 ligand such as eotaxin
      induces migration of ASMC in vitro. These results may suggest that eotaxin could
      be involved in the increased smooth muscle mass observed in asthmatics through
      the activation of CCR3.

PMID- 16081848
TI  - Spontaneous immunity against Bcl-xL in cancer patients.
AB  - It is well-established that peptide epitopes derived from human tumor-associated
      Ags can be recognized by CTL in the context of the MHC molecule. However, the
      vast majority of Ags described are not vital for survival and growth of the tumor
      cells, and immunoselection of Ag-loss variants during immunotherapy has been
      demonstrated in several cases. Malfunctions in death pathways observed in human
      cancers are often due to overexpression of antiapoptotic proteins in the Bcl-2
      protein family, i.e., Bcl-2, Mcl-1, and Bcl-xL. These antiapoptotic proteins are
      implicated in cancer development, tumor progression, and drug resistance. The
      general overexpression of the antiapoptotic members of the Bcl-2 family in cancer
      and the fact that down-regulation or loss of expression of these proteins as a
      means of immune escape would impair sustained tumor growth makes them very
      attractive targets for anticancer immunotherapy. Recently, we identified
      spontaneous T cell responses against Bcl-2- and Mcl-1-derived peptides in
      patients suffering from cancers of different origin. In this study, we
      demonstrate that Bcl-xL is a target for T cell recognition in cancer patients.
      Thus, we describe spontaneous HLA-A2-restricted cytotoxic T cell responses
      against peptide epitopes derived from Bcl-xL by means of ELISPOT and flow
      cytometry stainings, whereas no responses were detected against any of the Bcl-xL
      epitopes in any healthy controls. Moreover, Bcl-xL-specific T cells are cytotoxic
      against HLA-matched cancer cells of different origin. Thus, cellular immune
      responses against apoptosis inhibitors like the Bcl-2 family proteins appear to
      represent a general feature in cancer.

PMID- 16081849
TI  - Human bronchial epithelium controls TH2 responses by TH1-induced, nitric oxide
      mediated STAT5 dephosphorylation: implications for the pathogenesis of asthma.
AB  - Increased levels of NO in exhaled air in association with increased NO synthetase
      (NOS)2 expression in bronchial epithelial are hallmark features of asthma. It has
      been suggested that NO contributes to asthma pathogenesis by selective down
      regulation of TH1 responses. We demonstrate, however, that NO can reversibly
      limit in vitro expansion of both human TH1 and TH2 CD4+ T cells. Mechanistically,
      NO induces cGMP-mediated reversible STAT5 dephosphorylation and therefore
      interferes with the IL-2R activation cascade. Human bronchial epithelial cells
      (HBEC) up-regulate NOS2 after stimulation with IFN-gamma secreted by TH1 CD4+ T
      cells and release NO, which inhibits both TH1 and TH2 cell proliferation. This
      reversible T cell growth arrest depends on NO because T cell proliferation is
      completely restored after in vitro blocking of NOS2 on HBEC. HBEC thus drive the
      effector end of a TH1-controlled feedback loop, which protects airway mucosal
      tissues at the potential lesional site in asthma from overwhelming CD4+ TH2 (and
      potentially TH1) responses following allergen exposure. Variations in the
      efficiency of this feedback loop provides a plausible mechanism to explain why
      only a subset of atopics sensitized to ubiquitous aeroallergens progress to
      expression of clinically relevant levels of airways inflammation.

PMID- 16081850
TI  - TNF inhibition rapidly down-regulates multiple proinflammatory pathways in
      psoriasis plaques.
AB  - The mechanisms of action of marketed TNF-blocking drugs in lesional tissues are
      still incompletely understood. Because psoriasis plaques are accessible to repeat
      biopsy, the effect of TNF/lymphotoxin blockade with etanercept (soluble TNFR) was
      studied in ten psoriasis patients treated for 6 months. Histological response,
      inflammatory gene expression, and cellular infiltration in psoriasis plaques were
      evaluated. There was a rapid and complete reduction of IL-1 and IL-8
      (immediate/early genes), followed by progressive reductions in many other
      inflammation-related genes, and finally somewhat slower reductions in
      infiltrating myeloid cells (CD11c+ cells) and T lymphocytes. The observed
      decreases in IL-8, IFN-gamma-inducible protein-10 (CXCL10), and MIP-3alpha
      (CCL20) mRNA expression may account for decreased infiltration of neutrophils, T
      cells, and dendritic cells (DCs), respectively. DCs may be less activated with
      therapy, as suggested by decreased IL-23 mRNA and inducible NO synthase mRNA and
      protein. Decreases in T cell-inflammatory gene expression (IFN-gamma, STAT-1,
      granzyme B) and T cell numbers may be due to a reduction in DC-mediated T cell
      activation. Thus, etanercept-induced TNF/lymphotoxin blockade may break the
      potentially self-sustaining cycle of DC activation and maturation, subsequent T
      cell activation, and cytokine, growth factor, and chemokine production by
      multiple cell types including lymphocytes, neutrophils, DCs, and keratinocytes.
      This results in reversal of the epidermal hyperplasia and cutaneous inflammation
      characteristic of psoriatic plaques.

PMID- 16081851
TI  - Delivery of dendritic cells engineered to secrete IFN-alpha into central nervous
      system tumors enhances the efficacy of peripheral tumor cell vaccines: dependence
      on apoptotic pathways.
AB  - We tested whether modulation of the CNS-tumor microenvironment by delivery of IFN
      alpha-transduced dendritic cells (DCs: DC-IFN-alpha) would enhance the
      therapeutic efficacy of peripheral vaccinations with cytokine-gene transduced
      tumor cells. Mice bearing intracranial GL261 glioma or MCA205 sarcoma received
      peripheral immunizations with corresponding irradiated tumor cells engineered to
      express IL-4 or GM-CSFs, respectively, as well as intratumoral delivery of DC-IFN
      alpha. This regimen prolonged survival of the animals and induced tumor-specific
      CTLs that expressed TRAIL, which in concert with perforin and Fas ligand (FasL)
      was involved in the tumor-specific CTL activity of these cells. The in vivo
      antitumor activity associated with this approach was abrogated by administration
      of neutralizing mAbs against TRAIL or FasL and was not observed in perforin-/-,
      IFN-gamma-/-, or FasL-/- mice. Transduction of the tumor cells with antiapoptotic
      protein cellular FLIP rendered the gene-modified cells resistant to TRAIL- or
      FasL-mediated apoptosis and to CTL killing activity in vitro. Furthermore, the
      combination therapeutic regimen was ineffective in an intracranial cellular FLIP
      transduced MCA205 brain tumor model. These results suggest that the combination
      of intratumoral delivery of DC-IFN-alpha and peripheral immunization with
      cytokine-gene transduced tumor cells may be an effective therapy for brain tumors
      that are sensitive to apoptotic signaling pathways.

PMID- 16081852
TI  - Activation of thymic regeneration in mice and humans following androgen blockade.
AB  - The thymus undergoes age-related atrophy, coincident with increased circulating
      sex steroids from puberty. The impact of thymic atrophy is most profound in
      clinical conditions that cause a severe loss in peripheral T cells with the
      ability to regenerate adequate numbers of naive CD4+ T cells indirectly
      correlating with patient age. The present study demonstrates that androgen
      ablation results in the complete regeneration of the aged male mouse thymus,
      restoration of peripheral T cell phenotype and function and enhanced thymus
      regeneration following bone marrow transplantation. Importantly, this technique
      is also applicable to humans, with analysis of elderly males undergoing sex
      steroid ablation therapy for prostatic carcinoma, demonstrating an increase in
      circulating T cell numbers, particularly naive (TREC+) T cells. Collectively
      these studies represent a fundamentally new approach to treating immunodeficiency
      states in humans.

PMID- 16081853
TI  - Gene transfer with microbubble ultrasound and plasmid DNA into skeletal muscle of
      mice: comparison between commercially available microbubble contrast agents.
AB  - PURPOSE: To compare three commercial microbubble contrast agents (Optison,
      SonoVue, and Levovist) for their effect on gene delivery in skeletal muscle in
      conjunction with the use of therapeutic ultrasound. MATERIALS AND METHODS: The
      study was approved by the Animal Care and Use Committee. Plasmid DNA (10 microg)
      encoding green fluorescent protein (GFP) was mixed with microbubbles (or saline
      control) and injected into the tibialis anterior muscle of mice with and without
      adjunct ultrasound (1 MHz, 2 W/cm2, 30 seconds, 20% duty cycle). The efficiencies
      of GFP transgene expression were determined with four experimental conditions:
      (a) plasmid and saline as control (six mice), (b) plasmid and Optison (six mice),
      (c) plasmid and SonoVue (four mice), and (d) plasmid and Levovist (air based,
      four mice). The right legs were exposed to ultrasound, while the left legs were
      unexposed. Transfection efficiency was assessed by counting the number of GFP
      positive fibers. Tissue damage was assessed by measuring the maximal-damage area
      on serial sections. RESULTS: When ultrasound was applied, both SonoVue and
      Optison significantly improved (P < .05) gene transfection efficiency. Optison
      was also effective (P < .05) even when no ultrasound was applied, which is
      consistent with previous studies. Levovist without ultrasound decreased the level
      of transfection (P < .05), with increased tissue damage. CONCLUSION: Both non-air
      based agents show promise in gene delivery in skeletal muscle with undetectable
      tissue damage. Enhanced gene transfer with additional ultrasound was achieved
      only with SonoVue.

PMID- 16081854
TI  - Optimizing cutoff scores for the Barthel index and the modified Rankin scale for
      defining outcome in acute stroke trials.
AB  - BACKGROUND AND PURPOSE: There is little agreement on how to assess outcome in
      acute stroke trials. Cutoff scores for the Barthel Index (BI) and modified Rankin
      Scale (mRS) are frequently arbitrarily chosen to dichotomize favorable and
      unfavorable outcome. We investigated sensitivity and specificity of BI cutoff
      scores in relation to the mRS to obtain the optimal corresponding BI and mRS
      scores. METHODS: BI and mRS scores were collected from 1034 ischemic stroke
      patients. Sensitivity and specificity were calculated for BI cutoff scores from
      45 to 100 in mRS score 1, 2, and 3 and were plotted in receiver operator
      characteristic (ROC) curves. RESULTS: The cutoff scores for the BI with the
      highest sum of sensitivity and specificity were 95 (sensitivity 85.6%;
      specificity 91.7%), 90 (sensitivity 90.7%; specificity 88.1%), and 75
      (sensitivity 95.7%; specificity, 88.5%) for, respectively, mRS 1, 2, and 3. The
      area under the ROC curve was 0.933 in mRS 1, 0.960 in mRS 2, and 0.979 in mRS 3.
      CONCLUSIONS: The optimal cutoff scores for the BI were 95 for mRS 1, 90 for mRS
      2, and 75 for mRS 3. For future acute stroke trials that assess stroke outcome
      with the BI and mRS, we recommend the use of these BI cutoff score(s) with the
      corresponding mRS cutoff score(s), to ensure the use of consistent and uniform
      end points.

PMID- 16081855
TI  - Chagas disease is an independent risk factor for stroke: baseline characteristics
      of a Chagas Disease cohort.
AB  - BACKGROUND AND PURPOSE: Chagas disease (CD) is frequently associated with
      cardioembolic stroke in South America. Our objective was to identify the
      predictors of stroke in a region where CD is endemic. METHODS: We screened 305
      consecutive cardiopathy patients. Significant predictors of stroke in univariable
      analyses were included in a multivariable model. RESULTS: Stroke was more
      frequent in CD (15.0%) compared with other cardiopathies (6.3%; P=0.015). Other
      predictors of stroke in univariable analyses were previous diabetes or
      cardioversion and use of amiodarone, antiplatelet agents, and warfarin. In
      multivariable analysis, remaining predictors of stroke were CD (odds ratio [OR],
      1.09; 95% CI, 1.02 to 1.17), cardioversion (OR, 1.07; 95% CI, 1.02 to 1.13), and
      diabetes (OR, 1.12; 95% CI, 1.01 to 1.24). CONCLUSIONS: In conclusion, CD is a
      risk factor for stroke, independent of systolic dysfunction or presence of
      cardiac arrhythmias.

PMID- 16081856
TI  - Ischemic and hemorrhagic strokes in Dakar, Senegal: a hospital-based study.
AB  - BACKGROUND AND PURPOSE: Basic stroke features are hardly known in sub-Saharan
      countries, and no data are available in Senegal. METHODS: We performed a
      retrospective hospital-based study in Dakar, Senegal, to assess risk factors and
      etiology of stroke. Patients were recruited from January 1, 2003, to July 31,
      2004, at the Hopital Principal, Dakar. Strokes had to be ascertained by computed
      tomography. RESULTS: A total of 107 patients were studied. Seventy percent of
      strokes were of ischemic nature. For ischemic strokes, mean age was 64.2 years.
      Hypertension was the main risk factor, occurring in 68%, and diabetes was
      encountered in 37.3%. Lacunar strokes and cardioembolism accounted for 20% and
      13.3%, respectively. Because of the lack of systematic investigations, two thirds
      of strokes were of undetermined origin. Mortality within 1 month was 38%. For
      hemorrhagic strokes, mean age was 51 years and 1 month mortality was 56%.
      CONCLUSIONS: Hypertension is the main risk factor for both ischemic and
      hemorrhagic strokes in this hospital-based study.

PMID- 16081857
TI  - 3D ultrasound measurement of change in carotid plaque volume: a tool for rapid
      evaluation of new therapies.
AB  - BACKGROUND AND PURPOSE: New therapies are being developed that are
      antiatherosclerotic but that lack intermediate end points, such as changes in
      plasma lipids, which can be measured to test efficacy. To study such treatments,
      it will be necessary to directly measure changes in atherosclerosis. The study
      was designed to determine sample sizes needed to detect effects of treatment
      using 3D ultrasound (US) measurement of carotid plaque. METHODS: In 38 patients
      with carotid stenosis >60%, age+/-SD 69.42+/-7.87 years, 15 female, randomly
      assigned in a double-blind fashion to 80 mg atorvastatin daily (n=17) versus
      placebo (n=21), we measured 3D plaque volume at baseline and after 3 months by
      disc segmentation of voxels representing carotid artery plaque, after 3D
      reconstruction of parallel transverse duplex US scans into volumetric 3D data
      sets. RESULTS: There were no significant differences in baseline risk factors.
      The rate of progression was 16.81+/-74.10 mm3 in patients taking placebo versus
      regression of -90.25+/-85.12 mm3 in patients taking atorvastatin (P<0.0001).
      CONCLUSIONS: 3D plaque volume measurement can show large effects of therapy on
      atherosclerosis in 3 months in sample sizes of approximately 20 patients per
      group. Sample sizes of 22 per group would be sufficient to show an effect size of
      25% that of atorvastatin in 6 months. This technology promises to be very useful
      in evaluation of new therapies.

PMID- 16081858
TI  - Role of the bloodstream impacting force and the local pressure elevation in the
      rupture of cerebral aneurysms.
AB  - BACKGROUND AND PURPOSE: Inertial force of the bloodstream results in the local
      elevation of intravascular pressure secondary to flow impact. Previous studies
      suggest that this "impacting force" and the local pressure elevation at the
      aneurysm may have a large contribution to the development of cerebral aneurysms.
      The goal of the present study is to evaluate how the bloodstream impacting force
      and the local pressure elevation at the aneurysm influences the rupture of
      cerebral aneurysms. METHODS: A total of 29 aneurysms were created in 26 patient
      specific vessel models, and computer simulations were used to calculate pressure
      distributions around the vessel branching points and the aneurysms. RESULTS:
      Direct impact of the parent artery bloodstream resulted in local elevation in
      pressure at branch points, and bends in arteries (231.2+/-198.1 Pa; 100 Pa=0.75
      mm Hg). The bloodstream entered into the aneurysm with a decreased velocity after
      it impacted on the branching points or bends. Thus, the flow impact at the
      aneurysm occurred usually weakly. At the top or the rupture point of the
      aneurysm, the flow velocity was always delayed. The local pressure elevation at
      the aneurysm was 119.3+/-91.2 Pa. CONCLUSIONS: The pressure elevation at the area
      of flow impact and at the aneurysm constituted only 1% to 2% of the peak
      intravascular pressure. The results suggest that the bloodstream impacting force
      and the local pressure elevation at the aneurysm may have less contribution to
      the rupture of cerebral aneurysms than was expected previously.

PMID- 16081859
TI  - Community-based stroke incidence in a Scottish population: the Scottish Borders
      Stroke Study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the incidence
      and case fatality of stroke in a geographically defined region of Scotland, a
      nation with a high cardiovascular risk. METHODS: All strokes occurring in
      residents of the Scottish Borders (population 106,352) were identified during a
      24-month period from 1998 to 2000 using multiple overlapping methods of case
      ascertainment. Standard criteria were used to define stroke and case fatality.
      Stroke subtypes were determined by computer tomography (CT) scan, MRI, or
      autopsy. RESULTS: 790 strokes were identified; 596 were first-ever-in-a-lifetime
      strokes (FES). 91.1% of FES underwent CT scan and/or autopsy. The crude annual
      incidence rate per 100,000 per year was: 280 (95% CI, 258 to 304) overall, 197
      (95% CI 179-217) cerebral infarction, 24 (95% CI 17-31) intracerebral
      haemorrhage, 11 (95% CI 7-16) subarachnoid haemorrhage and 49 (95% CI 40-59)
      undetermined stroke. 28 day FES case fatality was 15.9% (95% CI, 13.2 to 19.1)
      increasing to 26.3% (95% CI, 23.0 to 30.0) at 1 year. Comparing 18 previous
      worldwide incidence studies with the SBSS showed a similar relative risk of
      stroke incidence and case fatality for FES and FES subtypes. CONCLUSIONS: The
      SBSS crude incidence rate is one of the highest in the world but age-adjusted
      rates, case fatality and relative risk for all stroke and stroke subtypes were
      not significantly different from the majority of previous studies. Unlike
      cardiovascular disease, the Scottish risk of stroke would appear to be similar to
      other populations worldwide.

PMID- 16081860
TI  - Use of time by stroke patients: a comparison of four European rehabilitation
      centers.
AB  - BACKGROUND AND PURPOSE: Differences exist between European countries in the
      proportion of patients who die or become dependent after stroke. The aim of the
      present study was to identify differences in the use of time by stroke patients
      in 4 rehabilitation centers in 4 European countries. METHODS: In each of the 4
      centers, 60 randomly selected stroke patients were observed at 10-minute
      intervals using behavioral mapping. Observations took place on 30 weekdays
      selected at random, on equal numbers of morning, afternoon, and evening sessions.
      A logistic generalized estimating equation model with correction for differences
      in case mix and multiple testing was used for the analysis. RESULTS: Overall time
      available from different professions was the highest in the United Kingdom, but
      patients in the United Kingdom spent on average only 1 hour per day in therapy.
      This was significantly less than patients in Belgium and Germany, who spent
      approximately 2 hours, and patients in Switzerland who spent approximately 3
      hours per day in therapy. In all centers, patients spent less than half their
      time in interactions and >72% of the time in nontherapeutic activities.
      CONCLUSIONS: Important differences in the use of time were established, which
      appeared dependent on management decisions rather than the number of staff
      available. Patients in the Swiss and German centers spent more time in therapy,
      possibly because of the structured organization of rehabilitation. Further
      studies will verify whether this has an effect on outcome.

PMID- 16081861
TI  - Supratentorial age-related white matter changes predict outcome in cerebellar
      stroke.
AB  - BACKGROUND AND PURPOSE: Little is known about the relevance of age related white
      matter lesions (WMLs) concerning outcome after first-ever territorial stroke.
      Based on an index patient, we hypothesized that age and pre-existent WMLs rather
      than infarct volume and topography determine outcome. PATIENTS AND METHODS:
      Thirty-four consecutive patients with magnetic resonance diffusion-weighted
      imaging-proven isolated acute cerebellar infarction were prospectively entered on
      our stroke data registry. Patients with pre-existent neurological deficits,
      hemorrhagic, or malignant cerebellar infarction were excluded. Patients were
      stratified using Rankin and Barthel disability scales into groups: I complete
      recovery, II moderate, and III significant disability 14 days after stroke onset.
      RESULTS: Initial neurological and functional scores were similar among all the
      groups with vertigo, nausea, unsteadiness, and limb ataxia being the most common.
      Infarct volume, vascular territories, and comorbidity did not predict clinical
      outcome. In contrast, presence and severity of supratentorial WMLs and age
      significantly determined outcome by functional tests. CONCLUSIONS: In patients
      with isolated cerebellar infarction functional outcome correlated with the
      coexistence of age-related WMLs rather than stroke volume and topography. This
      reflects the loss of compensatory network integrity as the equivalent of
      functional incapacity beyond local lesion disturbances.

PMID- 16081862
TI  - Leisure time, occupational, and commuting physical activity and the risk of
      stroke.
AB  - BACKGROUND AND PURPOSE: The role of physical activity, especially that of
      occupational and commuting physical activity, in the prediction of stroke risk is
      not properly established. We assessed the relationship of different types of
      physical activity with total and type-specific stroke risk. METHODS: We
      prospectively followed 47 721 Finnish subjects 25 to 64 years of age without a
      history of coronary heart disease, stroke, or cancer at baseline. Hazard ratios
      (HRs) for incident stroke were estimated for different levels of leisure time,
      occupational, and commuting physical activity. RESULTS: During a mean follow-up
      of 19.0 years, 2863 incident stroke events were ascertained. The multivariate
      adjusted (age, sex, area, study year, body mass index, systolic blood pressure,
      cholesterol, education, smoking, alcohol consumption, diabetes, and other 2 types
      of physical activity) HRs associated with low, moderate, and high leisure time
      physical activity were 1.00, 0.86, and 0.74 (Ptrend<0.001) for total stroke,
      1.00, 0.87, and 0.46 (Ptrend=0.011) for subarachnoid hemorrhage, 1.00, 0.77, and
      0.63 (Ptrend=0.024) for intracerebral hemorrhage, and 1.00, 0.87, and 0.80
      (Ptrend=0.001) for ischemic stroke, respectively. The multivariate-adjusted HRs
      associated with none, 1 to 29, and > or =30 minutes of active commuting were
      1.00, 0.92, and 0.89 (Ptrend=0.043) for total stroke, and 1.00, 0.93, and 0.86
      (Ptrend=0.028) for ischemic stroke, respectively. Occupational activity had a
      modest association with ischemic stroke in the multivariate analysis
      (Ptrend=0.046). CONCLUSIONS: A high level of leisure time physical activity
      reduces the risk of all subtypes of stroke. Daily active commuting also reduces
      the risk of ischemic stroke.

PMID- 16081863
TI  - Alcohol use and risk of ischemic stroke among older adults: the cardiovascular
      health study.
AB  - BACKGROUND AND PURPOSE: The association of light to moderate alcohol consumption
      with risk of ischemic stroke remains uncertain, as are the roles of potentially
      mediating factors and modification by apolipoprotein E (apoE) genotype. METHODS:
      We studied the prospective association of alcohol consumption and risk of
      ischemic stroke among 4410 participants free of cardiovascular disease at
      baseline in the Cardiovascular Health Study, a population-based cohort study of
      older adults from 4 US communities. Participants reported their consumption of
      alcoholic beverages yearly. RESULTS: During an average follow-up period of 9.2
      years, 434 cases of incident ischemic stroke occurred. Compared with long-term
      abstainers, the multivariate relative risks of ischemic stroke were 0.85 (95% CI,
      0.63 to 1.13), 0.75 (95% CI, 0.53 to 1.06), 0.82 (95% CI, 0.51 to 1.30), and 1.03
      (95% CI, 0.68 to 1.57) among consumers of <1, 1 to 6, 7 to 13, and > or =14
      drinks per week (P quadratic trend 0.06). ApoE genotype appeared to modify the
      alcohol-ischemic stroke relationship (P interaction 0.08), with generally lower
      risks among drinkers than abstainers in apoE4-negative participants but higher
      risks among drinkers than abstainers among apoE4-positive participants. We could
      not identify candidate mediators among lipid, inflammatory, and prothrombotic
      factors. CONCLUSIONS: In this study of older adults, the association of alcohol
      use and risk of ischemic stroke was U-shaped, with modestly lower risk among
      consumers of 1 to 6 drinks per week. However, apoE genotype may modify this
      association, and even moderate alcohol intake may be associated with an increased
      risk of ischemic stroke among apoE4-positive older adults.

PMID- 16081864
TI  - MRI screening before standard tissue plasminogen activator therapy is feasible
      and safe.
AB  - BACKGROUND AND PURPOSE: MRI screening for thrombolytic therapy may improve
      patient selection. Alternatively, it may excessively delay treatment and thereby
      lead to worse outcomes. We hypothesized that times to treatment and outcomes in a
      stroke center with immediate MRI access and interpretation would not differ from
      those of the typical clinical practice. METHODS: We compared the results of 120
      consecutive patients treated with intravenous tissue plasminogen activator (tPA)
      within 3 hours of onset at our center with those of the 2 largest multicenter
      registries of tPA use. In addition to standard criteria, MRI specific eligibility
      criteria were applied in 97 patients. MRI was not performed in 23 patients
      because of contraindications to MRI or late patient arrival (>2.5 hours).
      Outcomes were the modified Rankin Scale (mRS) obtained at 3 months. RESULTS:
      Times to treatment (median door-to-needle time 81.5 minutes; median onset-to
      needle time 135 minutes) and outcomes (mRS 0 to 1, 40.8%; mRS 0 to 2, 47.5%) were
      not inferior to those of the typical clinical practice. Door-to-needle time was
      shorter in computed tomography (CT) screening (67.5+/-22.5 minutes; n=23) than in
      MRI screening (86.8+/-21.5 minutes; n=97; P<0.001). However, outcomes were not
      different between MRI screening (mRS 0 to 1, 42.3%; mRS 0 to 2, 49.5%) and CT
      screening (mRS 0 to 1, 34.8%; mRS 0 to 2, 39.1%). Neither times to treatment nor
      MRI screening was predictive of outcomes. CONCLUSIONS: These data demonstrate
      that MRI screening before tPA therapy is feasible and not associated with
      unacceptable times to treatment or outcomes.

PMID- 16081866
TI  - Is prehypertension a risk factor for cardiovascular diseases?
AB  - BACKGROUND AND PURPOSE: The Joint National Committee on High Blood Pressure
      identified a new category of blood pressure in adults termed prehypertension. Our
      objective was to determine the long-term risk of cardiovascular diseases
      associated with this new category in a well-defined cohort of adults. METHODS: We
      evaluated the association of prehypertension (120 to 139/80 to 89 mm Hg) and
      hypertension (>140/90 mm Hg) with the incidence of atherothrombotic brain
      infarction (ABI), all strokes, myocardial infarction (MI), and coronary artery
      disease (CAD) using pooled repeated measures and Cox proportional hazards
      analyses during follow-up after adjusting for age, gender, obesity, diabetes
      mellitus, hypercholesterolemia, cigarette smoking, and study period in a cohort
      of 5181 persons who participated in the Framingham Study. RESULTS: Among the
      11,116 person observations with a mean follow-up period of 9.9+/-1.0 years,
      prehypertension was not associated with an increased risk for ABI (relative risk
      [RR], 2.2; 95% CI, 0.5 to 9.3). Among the 11,802 person observations with a mean
      follow-up period of 9.7+/-1.5 years, prehypertension was associated with an
      increased risk for MI (RR, 3.5; 95% CI, 1.6 to 7.5). Prehypertension was also
      associated with an increased risk of CADs among the 11,570 person observations
      (RR, 1.7; 95% CI, 1.2 to 2.4). CONCLUSIONS: Prehypertension appears to be
      associated with an increased risk of MI and CAD but not stroke. Further studies
      are required to confirm the anticipated benefits of identifying and intervening
      in persons with prehypertension.

PMID- 16081867
TI  - Major risk factors for intracerebral hemorrhage in the young are modifiable.
AB  - BACKGROUND AND PURPOSE: To identify risk factors for intracerebral hemorrhage
      (ICH), we examined data from the Hemorrhagic Stroke Project (HSP), a case-control
      study of hemorrhagic stroke among men and women aged 18 to 49 years. METHODS:
      Case subjects for the HSP were recruited from 44 hospitals in the United States.
      Eligibility criteria included an ICH within 30 days preceding enrollment, no
      history of stroke or known brain lesion. For this report, we focused on patients
      with primary ICH, defined as not associated with an aneurysm, arteriovenous
      malformation or other structural lesion. Two control subjects were sought for
      each case subject. A multivariate regression analysis was performed to determine
      risk factors for primary ICH. RESULTS: A total of 1714 patients with hemorrhagic
      stroke were identified for participation in the HSP. Of these, 217 cases met the
      criteria for primary ICH. Cases with primary ICH were matched to 419 controls.
      Independent risk factors for ICH included hypertension (adjusted odds ratio [OR],
      5.71; 95% CI, 3.61 to 9.05), diabetes (adjusted OR, 2.40; 95% CI, 1.15 to 5.01),
      menopause (adjusted OR, 2.50; 95% CI, 1.06 to 5.88), current cigarette smoking
      (adjusted OR, 1.58; 95% CI, 1.02 to 2.44), alcoholic drinks> or =2/day (adjusted
      OR, 2.23; 95% CI, 1.16 to 4.32), caffeinated drinks> or =5/day (adjusted OR,
      1.73; 95% CI, 1.08 to 2.79), and caffeine in drugs (adjusted OR, 3.55; 95% CI,
      1.24 to 10.20). CONCLUSIONS: Among young men and women, the major risk factors
      for primary ICH can be modified, suggesting that this type of stroke may be
      preventable. Our findings for caffeine and menopause warrant further study.

PMID- 16081868
TI  - Cigarette smoking among spouses: another risk factor for stroke in women.
AB  - BACKGROUND AND PURPOSE: It is well known that passive exposure to cigarette
      smoking increases the risk of coronary events, but the effect on the risk of
      stroke is not well defined. We performed this study to determine the effect of
      cigarette smoking among spouses on the risk of developing stroke and ischemic
      stroke among a nationally representative sample of women. METHODS: We examined
      the association between history of smoking among spouses with the incidence of
      stroke in a national cohort of 5379 women who participated in the First National
      Health and Nutrition Examination Survey Epidemiologic Follow-Up Study. RESULTS:
      During a mean follow-up of 8.5 years, the risk was significantly increased for
      all strokes (relative risk, 5.7; 95% CI, 1.4 to 24) and ischemic stroke (relative
      risk, 4.8; 95% CI, 1.2 to 20) among cigarette-smoking women with a cigarette
      smoking spouse compared with those with a nonsmoking spouse after adjusting for
      other cardiovascular risk factors. CONCLUSIONS: The study provides new evidence
      linking spousal smoking to stroke.

PMID- 16081869
TI  - Aldosterone and angiotensin II synergistically induce mitogenic response in
      vascular smooth muscle cells.
AB  - Interaction between aldosterone (Aldo) and angiotensin II (Ang II) in the
      cardiovascular system has been highlighted; however, its detailed signaling
      mechanism is poorly understood. Here, we examined the cross-talk of growth
      promoting signaling between Aldo and Ang II in vascular smooth muscle cells
      (VSMC). Treatment with a lower dose of Aldo (10(-12) mol/L) and with a lower dose
      of Ang II (10(-10) mol/L) significantly enhanced DNA synthesis, whereas Aldo or
      Ang II alone at these doses did not affect VSMC proliferation. This effect of a
      combination of Aldo and Ang II was markedly inhibited by a selective AT1 receptor
      blocker, olmesartan, a mineralocorticoid receptor antagonist, spironolactone, an
      MEK inhibitor, PD98059, or an EGF receptor tyrosine kinase inhibitor, AG1478.
      Treatment with Aldo together with Ang II, even at noneffective doses,
      respectively, synergistically increased extracellular signal-regulated kinase
      (ERK) activation, reaching 2 peaks at 10 to 15 minutes and 2 to 4 hours. The
      early ERK peak was effectively blocked by olmesartan or an EGF receptor kinase
      inhibitor, AG1478, but not by spironolactone, whereas the late ERK peak was
      completely inhibited by not only olmesartan, but also spironolactone. Combined
      treatment with Aldo and Ang II attenuated mitogen-activated protein kinase
      phosphatase-1 (MKP-1) expression and increased Ki-ras2A expression. The late ERK
      peak was not observed in VSMC treated with Ki-ras2A-siRNA. Interestingly, the
      decrease in MKP-1 expression and the increase in Ki-ras2A expression were
      restored by PD98059 or AG1478. These results suggest that Aldo exerts a
      synergistic mitogenic effect with Ang II and support the notion that blockade of
      both Aldo and Ang II could be more effective to prevent vascular remodeling.

PMID- 16081870
TI  - Sarco/endoplasmic reticulum Ca2+-ATPase gene transfer reduces vascular smooth
      muscle cell proliferation and neointima formation in the rat.
AB  - Proliferation of vascular smooth muscle cells (VSMC) is a primary cause of
      vascular disorders and is associated with major alterations in Ca2+ handling
      supported by loss of the sarco/endoplasmic reticulum calcium ATPase, SERCA2a. To
      determine the importance of SERCA2a in neointima formation, we have prevented
      loss of its expression by adenoviral gene transfer in a model of balloon injury
      of the rat carotid artery. Two weeks after injury, the intima/media ratio was
      significantly lower in SERCA2a-infected than in injured noninfected or injured
      beta-galactosidase-infected carotids (0.29+/-0.04 versus 0.89+/-0.19 and 0.72+/
      0.14, respectively; P<0.05), and was comparable to that observed in control
      carotids (0.21+/-0.03). The pathways leading to proliferation were analyzed in
      serum-stimulated VSMC. Forced expression of SERCA2a arrested cell cycle at the G1
      phase and prevented apoptosis. SERCA2a inhibits proliferation through
      inactivation of calcineurin (PP2B) and its target transcription factor NFAT
      (nuclear factor of activated T-cells) resulting in lowering of cyclin D1 and pRb
      levels. By using NFAT-competing peptide VIVIT, we showed that NFAT activity is
      strongly required to promote VSMC proliferation. In conclusion, we provide the
      first evidence that increasing SERCA2a activity inhibits VSMC proliferation and
      balloon injury-induced neointima formation.

PMID- 16081871
TI  - Depletion of serum response factor by RNA interference mimics the mitogenic
      effects of platelet derived growth factor-BB in vascular smooth muscle cells.
AB  - Promoters of many smooth muscle-specific genes (SM-genes) contain multiple CArG
      boxes, which represent a binding site for serum response factor (SRF).
      Transcriptional control through these regions involves interactions with SRF and
      specific coactivators such as myocardin. We have previously reported that
      suppression of SM-gene expression by platelet derived growth factor (PDGF) is
      associated with redistribution of SRF, leading to lower intra-nuclear levels, and
      a reduction in SRF transactivation. To further assess the role of SRF depletion
      on VSMC phenotype, the current study used RNA interference (RNAi). Two SRF
      specific sequences constructed as hairpins were stably expressed in rat VSMC.
      Clones expressing SRF RNAi had no detectable SRF expression by immunoblotting,
      and showed diminished levels of SM alpha-actin protein and promoter activity.
      Unexpectedly, depletion of VSMC resulted in increased rates of proliferation and
      migration. Several genes whose expression is increased by PDGF stimulation,
      including c-Jun, were similarly induced in cells lacking SRF. Effects of SRF
      depletion were not attributable to altered PDGF receptor activity or alterations
      in activation of Akt. These data indicate that loss of SRF transactivation in
      VSMC, in this case through suppression via RNAi, induces biological responses
      similar to that seen with PDGF.

PMID- 16081872
TI  - PKCalpha activates eNOS and increases arterial blood flow in vivo.
AB  - Endothelial nitric oxide synthase (eNOS) plays an important role in control of
      vascular tone and angiogenesis among other functions. Its regulation is complex
      and has not been fully established. Several studies have emphasized the
      importance of phosphorylation in the regulation of eNOS activity. Although it is
      commonly accepted that protein kinase C (PKC) signaling inhibits eNOS activity by
      phosphorylating Thr497 and dephosphorylating Ser1179, the distinct role of
      different PKC isoforms has not been studied so far. The PKC family comprises
      roughly 12 different isozymes that activate distinct downstream pathways. The
      present study was designed to investigate the role of PKCalpha isoform in
      regulation of eNOS activity. Overexpression of PKCalpha in primary endothelial
      cells was associated with increased eNOS-Ser1179 phosphorylation and increased NO
      production. Inhibition of PKCalpha activity either by siRNA transfection or by
      overexpression of a dominant negative mutant resulted in a marked decrease in
      FGF2-induced Ser1179 phosphorylation and NO production. In vivo, PKCalpha
      transduction in rat femoral arteries resulted in a significant increase in the
      resting blood flow that was suppressed by treatment with L-NAME, an eNOS
      inhibitor. In conclusion, these data demonstrate for the first time that PKCalpha
      stimulates NO production in endothelial cells and plays a role in regulation of
      blood flow in vivo.

PMID- 16081873
TI  - Targeting arterial chemoreceptor over-activity in heart failure with a gas.

PMID- 16081874
TI  - The shape of the electrical action-potential upstroke: a new aspect from optical
      measurements on the surface of the heart.

PMID- 16081875
TI  - Effect of inspiratory threshold loading on ventilatory kinetics during constant
      load exercise.
AB  - Humoral factors play an important role in the control of exercise hyperpnea. The
      role of neuromechanical ventilatory factors, however, is still being
      investigated. We tested the hypothesis that the afferents of the thoracopulmonary
      system, and consequently of the neuromechanical ventilatory loop, have an
      influence on the kinetics of oxygen consumption (VO2), carbon dioxide output
      (VCO2), and ventilation (VE) during moderate intensity exercise. We did this by
      comparing the ventilatory time constants (tau) of exercise with and without an
      inspiratory load. Fourteen healthy, trained men (age 22.6 +/- 3.2 yr) performed a
      continuous incremental cycle exercise test to determine maximal oxygen uptake
      (VO2max = 55.2 +/- 5.8 ml x min(-1) x kg(-1)). On another day, after unloaded
      warm-up they performed randomized constant-load tests at 40% of their VO2max for
      8 min, one with and the other without an inspiratory threshold load of 15 cmH2O.
      Ventilatory variables were obtained breath by breath. Phase 2 ventilatory
      kinetics (VO2, VCO2, and VE) could be described in all cases by a monoexponential
      function. The bootstrap method revealed small coefficients of variation for the
      model parameters, indicating an accurate determination for all parameters. Paired
      Student's t-tests showed that the addition of the inspiratory resistance
      significantly increased the tau during phase 2 of VO2 (43.1 +/- 8.6 vs. 60.9 +/-
      14.1 s; P < 0.001), VCO2 (60.3 +/- 17.6 vs. 84.5 +/- 18.1 s; P < 0.001) and VE
      (59.4 +/- 16.1 vs. 85.9 +/- 17.1 s; P < 0.001). The average rise in tau was 41.3%
      for VO2, 40.1% for VCO2, and 44.6% for VE. The tau changes indicated that
      neuromechanical ventilatory factors play a role in the ventilatory response to
      moderate exercise.

PMID- 16081876
TI  - Physical activity alters the brain Hsp72 and IL-1beta responses to peripheral E.
      coli challenge.
AB  - Physically active rats have facilitated heat shock protein 72 (Hsp72) responses
      after stressor exposure in both brain and peripheral tissues compared with
      sedentary rats. This study verifies that physically active animals do not have
      elevated Hsp72 levels compared with sedentary animals in the hypothalamus,
      pituitary, or dorsal vagal complex. We then examined whether 1) physically active
      rats respond more efficiently than sedentary rats to a bacterial challenge; 2)
      peripheral immune challenge elicits brain induction of Hsp72; 3) this induction
      is facilitated by prior freewheel running; and 4) Hsp72 upregulation produced by
      peripheral immune challenge results in a commensurate decrease in the
      proinflammatory cytokine IL-1beta. Adult male Fischer 344 rats were housed with
      either a mobile or locked running wheel. Six weeks later, rats were injected
      intraperitoneally with saline or Escherichia coli and killed 30 min, 2.5 h, 6 h,
      and 24 h later. Serum endotoxin and IL-1beta, and peritoneal fluid endotoxin and
      E. coli colony-forming units (CFUs) were measured. Hsp72 and IL-1beta were
      measured in hypothalamus, pituitary, and dorsal vagal complex. The results were
      that physically active rats had a faster reduction in endotoxin and E. coli CFUs
      and lower levels of circulating endotoxin and cytokines compared with sedentary
      rats. E. coli challenge elicited significantly greater time-dependent increases
      of both Hsp72 and IL-1beta in hypothalamus, pituitary, and dorsal vagal complex
      of physically active animals but not sedentary animals. Contrary to our
      hypothesis, increases in Hsp72 were positively correlated with IL-1beta. This
      study extends our findings that physical activity facilitates stress-induced
      Hsp72 to include immunological stressors such as bacterial challenge and suggests
      that brain Hsp72 and IL-1beta responses to peripheral immune challenge may
      contribute to exercise-mediated resistance to long-term sickness.

PMID- 16081877
TI  - Altered taste sensitivity in obese, prediabetic OLETF rats lacking CCK-1
      receptors.
AB  - Otsuka Long-Evans Tokushima fatty (OLETF) rats lack the CCK-1 receptor, are
      hyperphagic, progressively become obese, and develop type-2 diabetes. We recently
      demonstrated an increased preference for both real and sham feeding of sucrose in
      this strain, suggesting altered orosensory sensitivity. To investigate taste
      functions, we used an automated gustometer with 10-s access to different
      concentrations of various sapid stimuli. Tests were repeated at 10 and 18 wk of
      age to assess the early and advanced stages of prediabetes, respectively.
      Compared with age-matched, nonmutant controls, the OLETF rats showed higher
      avidity for sucrose at both ages. This difference increased as a function of age
      and tastant concentration. An exaggerated response also occurred for saccharin,
      alanine, and fructose, but not for Polycose. Similarly, OLETF rats consumed
      monosodium-glutamate more at the lower concentrations compared with controls, an
      effect that age also accentuated. In contrast, there was no statistical strain or
      age differences in responses to NaCl, MgCl2, citric acid, quinine-HCl, and the
      trigeminal stimulus capsaicin. These findings demonstrate that compared with
      controls, OLETF rats differ in their gustatory functions with an overall
      augmented sensitivity for sweet that progresses during prediabetes. This effect
      explains their overconsumption of sweet solutions and may contribute to the
      overall hyperphagia and obesity in this strain.

PMID- 16081878
TI  - Expanding the febrigenic role of cyclooxygenase-2 to the previously overlooked
      responses.
AB  - Previous studies on the role of cyclooxygenase (COX)-1 and -2 in fever induced by
      intravenous LPS have failed to investigate the role of these isoenzymes in the
      earliest responses: monophasic fever (response to a low, near-threshold dose of
      LPS) and the first phase of polyphasic fever (response to higher doses). We
      studied these responses in 96 mice that were COX-1 or COX-2 deficient (-/-) or
      sufficient (+/+). Each mouse was implanted with a temperature telemetry probe
      into the peritoneal cavity and a jugular catheter. The study was conducted at a
      tightly controlled, neutral ambient temperature (31 degrees C). To avoid stress
      hyperthermia (which masks the onset of fever), all injections were performed
      through a catheter extension. The +/+ mice responded to intravenous saline with
      no change in deep body temperature. To a low dose of LPS (1 microg/kg iv), they
      responded with a monophasic fever. To a higher dose (56 microg/kg), they
      responded with a polyphasic fever. Neither monophasic fever nor the first phase
      of polyphasic fever was attenuated in the COX-1 -/- mice, but both responses were
      absent in the COX-2 -/- mice. The second and third phases of polyphasic fever
      were also missing in the COX-2 -/- mice. The present study identifies a new,
      critical role for COX-2 in the mediation of the earliest responses to intravenous
      LPS: monophasic fever and the first phase of polyphasic fever. It also suggests
      that no product of the COX-1 gene, including the splice variant COX-1b (COX-3),
      is essential for these responses.

PMID- 16081879
TI  - Thermoregulatory responses to lipopolysaccharide in the mouse: dependence on the
      dose and ambient temperature.
AB  - Most published studies of thermoregulatory responses of mice to LPS involved a
      stressful injection of LPS, were run at a poorly controlled and often subneutral
      ambient temperature (T(a)), and paid little attention to the dependence of the
      response on the LPS dose. These pitfalls have been overcome in the present study.
      Male C57BL/6 mice implanted with jugular vein catheters were kept in an
      environmental chamber at a tightly controlled T(a). The relationship between the
      T(a)s used and the thermoneutral zone of the mice was verified by measuring tail
      skin temperature, either by infrared thermography or thermocouple thermometry.
      Escherichia coli LPS in a wide dose range (10(0)-10(4) microg/kg) was
      administered through an extension of the jugular catheter from outside the
      chamber. The responses observed were dose dependent. At a neutral T(a), low (just
      suprathreshold) doses of LPS (10(0)-10(1) microg/kg) caused a monophasic fever.
      To a slightly higher dose (10(1.5) microg/kg), the mice responded with a biphasic
      fever. To even higher doses (10(1.75)-10(4) microg/kg), they responded with a
      polyphasic fever, of which three distinct phases were identified. The dose
      dependence and dynamics of LPS fever in the mouse appeared to be remarkably
      similar to those seen in the rat. However, the thermoregulatory response of mice
      to LPS in a subthermoneutral environment is remarkably different from that of
      rats. Although very high doses of LPS (10(4) microg/kg) did cause a late
      (latency, approximately 3 h) hypothermic response in mice, the typical early
      (latency, 10-30 min) hypothermic response seen in rats did not occur. The present
      investigation identifies experimental conditions to study LPS-induced mono-, bi-,
      and polyphasic fevers and late hypothermia in mice and provides detailed
      characteristics of these responses.

PMID- 16081880
TI  - Comparative effects of dehydroepiandrosterone sulfate on ventricular diastolic
      function with young and aged female mice.
AB  - The adrenal steroid hormone dehydroepiandrosterone (DHEA) and its sulfated
      derivative [DHEA(S)] have been extensively studied for their potential anti-aging
      effects. Associated with aging, DHEA levels decline in humans, whereas other
      adrenal hormones remain unchanged, suggesting that DHEA may be important in the
      aging process. However, the effect of DHEA(S) supplementation on cardiac function
      in the aged has not been investigated. Therefore, we administered to young and
      old female mice a 60-day treatment with exogenous DHEA(S) at a dose of 0.1 mg/ml
      in the drinking water and compared the effects on left ventricular diastolic
      function and the myocardial extracellular matrix composition. The left
      ventricular stiffness (beta) was 0.30 +/- 0.06 mmHg/mul in the older control mice
      compared with 0.17 +/- 0.02 mmHg/mul in young control mice. Treatment with
      DHEA(S) decreased left ventricular stiffness to 0.12 +/- 0.03 mmHg/mul in the
      older mice and increased left ventricular stiffness to 0.27 +/- 0.04 mmHg/mul in
      young mice. The mechanism for the DHEA(S)-induced changes in diastolic function
      appeared to be associated with altered matrix metalloproteinase activity and the
      percentage of collagen cross-linking. We conclude that exogenous DHEA(S)
      supplementation is capable of reversing the left ventricular stiffness and
      fibrosis that accompanies aging, with a paradoxical increased ventricular
      stiffness in young mice.

PMID- 16081881
TI  - Diet-induced obesity and acute hyperlipidemia reduce IkappaBalpha levels in rat
      skeletal muscle in a fiber-type dependent manner.
AB  - Increased activity of proinflammatory/stress pathways has been implicated in the
      pathogenesis of insulin resistance in obesity. However, the effects of obesity on
      the activity of these pathways in skeletal muscle, the major insulin-sensitive
      tissue by mass, are poorly understood. Furthermore, the mechanisms that activate
      proinflammatory/stress pathways in obesity are unknown. The present study
      addressed the effects of diet-induced obesity (DIO; 6 wk of high-fat feeding) and
      acute (6-h) hyperlipidemia (HL) in rats on activity of IKK/IkappaB/NF-kappaB c
      Jun NH(2)-terminal kinase, and p38 MAPK in three skeletal muscles differing in
      fiber type [superficial vastus (Vas; fast twitch-glycolytic), soleus (Sol; slow
      twitch-oxidative), and gastrocnemius (Gas; mixed)]. DIO decreased the levels of
      the IkappaBalpha in Vas (24 +/- 3%, P = 0.001, n = 8) but not in Sol or Gas
      compared with standard chow-fed controls. Similar to DIO, HL decreased
      IkappaBalpha levels in Vas (26 +/- 5%, P = 0.006, n = 6) and in Gas (15 +/- 4%, P
      = 0.01, n = 7) but not in Sol compared with saline-infused controls. Importantly,
      the fiber-type-dependent effects on IkappaBalpha levels could not be explained by
      differential accumulation of triglyceride in Sol and Vas. HL, but not DIO,
      decreased phospho-p38 MAPK levels in Vas (41 +/- 7% P = 0.004, n = 6) but not in
      Sol or Gas. Finally, skeletal muscle c-Jun NH(2)-terminal kinase activity was
      unchanged by DIO or HL. We conclude that diet-induced obesity and acute HL reduce
      IkappaBalpha levels in rat skeletal muscle in a fiber-type-dependent manner.

PMID- 16081882
TI  - A functional mutation in the terminal exon of elastin in severe, early-onset
      chronic obstructive pulmonary disease.
AB  - We describe a novel variant in the terminal exon of human elastin, c.2318 G > A,
      resulting in an amino acid substitution of glycine 773 to aspartate (G773D) in a
      pedigree with severe early-onset chronic obstructive pulmonary disease (COPD).
      Transfection studies with elastin cDNAs demonstrate that the glycine to aspartate
      change compromises the ability of the mutant protein to undergo normal elastin
      assembly. Other functional consequences of this amino acid substitution include
      altered proteolytic susceptibility of the C-terminal region of elastin and
      reduced interaction of the exon 36 sequence with matrix receptors on cells. These
      results suggest that the G773D variant confers structural and functional
      consequences relevant to the pathogenesis of COPD.

PMID- 16081883
TI  - Requirement for tumor necrosis factor-receptor 2 in alveolar chemokine expression
      depends upon the form of the ligand.
AB  - Respiratory virus infection evokes a potent T-cell response that may result in a
      considerable insult to the structural and functional integrity of the gas
      exchange units of the lung. Alveolar antigen recognition by CD8+ T lymphocytes
      results in significant injury that is critically dependent upon tumor necrosis
      factor (TNF)-alpha expressed by the CD8+ T cells and is largely dependent upon
      TNF-receptor 1 expression on the alveolar epithelial target cells. TNF-receptor 2
      (TNF-R2)-deficient mice were used to demonstrate that CD8+ T-cell-mediated lung
      injury associated with clearance of experimental influenza requires TNF-R2 for
      full expression of immunopathology. In vitro analysis indicates that alveolar
      cell expression of TNF-R2 is critical in the induction of epithelial monocyte
      chemoattractant protein (MCP)-1 expression specifically in response to soluble
      TNF-alpha, suggesting an important role for this receptor in bystander lung
      injury. However, TNF-R2 was dispensable for induction of alveolar MCP-1
      expression in response to transmembrane TNF-alpha expressed by antigen-specific
      CD8+ T cells, and the effects of the two receptors seem to be additive. Because
      TNF-R2 may be rapidly shed as part of feedback inhibition of bystander
      inflammation, this suggests a mechanism by which immunopathology in respiratory
      virus infection may be regulated and by which T-cell receptor-dependent TNF-alpha
      activity might bypass such negative regulation for contact-dependent antiviral
      activities.

PMID- 16081884
TI  - Experimental infection of white-tailed deer with Anaplasma phagocytophilum,
      etiologic agent of human granulocytic anaplasmosis.
AB  - Serologic and molecular evidence of Anaplasma phagocytophilum has been
      demonstrated in white-tailed deer (WTD; Odocoileus virginianus), and deer are an
      important host for the tick vector Ixodes scapularis. In this study, we describe
      experimental infection of WTD with A. phagocytophilum. We inoculated four WTD
      with a human isolate of A. phagocytophilum propagated in tick cells. Two
      additional deer served as negative controls. All inoculated deer developed
      antibodies (titers, > or =64) to A. phagocytophilum, as determined by an indirect
      fluorescent antibody test, between 14 and 24 days postinfection [p.i.]), and two
      deer maintained reciprocal titers of > or =64 through the end of the 66-day
      study. Although morulae were not observed in granulocytes and A. phagocytophilum
      was not reisolated via tick cell culture of blood, 16S reverse transcriptase
      nested PCR (RT-nPCR) results indicated that A. phagocytophilum circulated in
      peripheral blood of three deer through at least 17 days p.i. and was present in
      two deer at 38 days p.i. Femoral bone marrow from one deer was RT-nPCR positive
      for A. phagocytophilum at 66 days p.i. There was no indication of clinical
      disease. These data confirm that WTD are susceptible to infection with a human
      isolate of A. phagocytophilum and verify that WTD produce detectable antibodies
      upon exposure to the organism. Because adults are the predominant life stage of
      I. scapularis found on deer and because adult I. scapularis ticks do not transmit
      A. phagocytophilum transovarially, it is unlikely that WTD are a significant
      source of A. phagocytophilum for immature ticks even though deer have a high
      probability of natural infection. However, the susceptibility and immunologic
      response of WTD to A. phagocytophilum render them suitable candidates as natural
      sentinels for this zoonotic tick-borne organism.

PMID- 16081885
TI  - Improvement of Lyme borreliosis serodiagnosis by a newly developed recombinant
      immunoglobulin G (IgG) and IgM line immunoblot assay and addition of VlsE and
      DbpA homologues.
AB  - We developed and evaluated a recombinant Borrelia line immunoblot assay based on
      18 homologues of seven different antigens, i.e., p100, p58, p41i, BmpA, VlsE,
      OspC, and DbpA. Each recombinant antigen can be detected separately and is
      distinct even from homologues with identical molecular weights. This blot was
      compared to the recently described recombinant Borrelia Western immunoblot assay
      (U. Schulte-Spechtel, G. Lehnert, G. Liegl, V. Fingerle, C. Heimerl, B. J.
      Johnson, and B. Wilske, J. Clin. Microbiol. 41:1299-1303, 2003). To verify
      sensitivity and specificity, both blots were evaluated for reactivity with
      Borrelia-specific immunoglobulin G (IgG) and IgM antibodies with 85 sera from
      patients with different manifestations of Lyme borreliosis and 110 controls.
      According to European interpretation criteria for Borrelia Western blots, which
      define a serum as positive when it recognizes at least two bands, sensitivity
      increased significantly from 70.6% (Western blot) to 84.7% (line blot) for IgG (P
      = 0.042) and from 40.0% (Western blot) to 73.8% (line blot) for IgM (P < 0.005).
      The increased sensitivity for IgG detection is due to the new line blot
      technique, whereas the improvement in detection of IgM is mainly achieved through
      incorporation of the additional antigens. Notably, the recombinant VlsE of
      Borrelia garinii strain PBi displayed the highest sensitivity of all antigens
      tested for IgG detection and is also one of the most useful antigens for IgM. Due
      to its excellent sensitivity and specificity combined with ease of evaluation,
      this line immunoblot assay offers a useful improvement in serodiagnosis of Lyme
      borreliosis.

PMID- 16081886
TI  - Prevalence of the ST239 clone of methicillin-resistant Staphylococcus aureus and
      differences in antimicrobial susceptibilities of ST239 and ST5 clones identified
      in a Korean hospital.
AB  - A total of 188 nonduplicate methicillin-resistant Staphylococcus aureus (MRSA)
      isolates obtained between 2001 and 2004 in a university hospital in Daegu, Korea,
      were analyzed for their clonal types by molecular typing techniques, including
      multilocus sequence typing, spaA typing, staphylococcal chromosomal cassette mec
      (SCCmec) typing, and pulsed-field gel electrophoresis (PFGE). They were examined
      for their antimicrobial susceptibilities. The majority (87%) of MRSA isolates
      belonged to sequence type 239 (ST239; n = 100; 53%) and ST5 (n = 63, 34%) on the
      basis of sequence typing. MRSA isolates belonging to ST239 were genotypically
      homogeneous, while those belonging to ST5 showed variations in spaA type, SCCmec
      type, and PFGE patterns. The rates of resistance of the MRSA isolates belonging
      to ST239 to trimethoprim, sulfamethoxazole, tobramycin, gentamicin, erythromycin,
      and tetracycline were significantly higher than those of the isolates belonging
      to ST5 (P < 0.05). This study demonstrated that the ST239 clone, while rarely
      detected in Korea, was prevalent and that the antimicrobial susceptibility of the
      ST239 clone was significantly different from that of the ST5 clone.

PMID- 16081887
TI  - Comparison of five repetitive-sequence-based PCR typing methods for molecular
      discrimination of Salmonella enterica isolates.
AB  - Five repetitive-element PCR (rep-PCR) techniques [primer sets ERIC1R-ERIC2 and
      REP1R-REP2I and primers ERIC2, BOXA1R, and (GTG)5] were evaluated for the
      discrimination of Salmonella enterica isolates at the serotype level. On the
      basis of number, even distribution over the whole fingerprint, and clarity of
      bands in the fingerprints, the enterobacterial repetitive intergenic consensus
      (ERIC) primer set and the (GTG)5 primer were chosen for use in the following
      experiments. For these two primer sets, reproducibility was tested on different
      lysates of five selected serotypes of Salmonella in the same PCR by using three
      different PCR runs. Reproducibility was poor between different PCR runs but high
      within the same PCR run. Furthermore, 80 different serotypes and five isolates
      which were not typeable by serotyping were fingerprinted. All strains were
      typeable by the ERIC primer set and the (GTG)5 primer and generated unique
      fingerprints, except for some strains with incomplete antigenic codes. Finally,
      55 genetically different strains belonging to 10 serotypes were fingerprinted to
      examine the genetic diversity of the rep-PCR within serotypes. This experiment
      showed that one serotype did not always correlate to only one ERIC or (GTG)5
      fingerprint but that the fingerprint heterogeneity within a serotype was limited.
      In epidemiological studies, ERIC- and/or (GTG)5-PCR can be used to limit the
      number of strains that have to be serotyped. The reproducibility of isolates in
      one PCR run, the discriminatory power, and the genetic diversity (stability) of
      the fingerprint were similar for the Eric primer set and the (GTG)5 primer, so
      both are equally able to discriminate Salmonella serotypes.

PMID- 16081888
TI  - Genotype distribution and molecular epidemiology of hepatitis C virus in blood
      donors from southeast France.
AB  - The genotype distribution of hepatitis C virus (HCV) in blood donors from
      southeast France was tracked for a period of 13 years (1991 to 2003). Virus
      genomes from 321 samples were analyzed by amplification and sequencing of the
      NS5b and E1 regions. The most frequent genotypes were 1b (30.2%), 1a (27.7%), and
      3a (22.4%). Although it was less common, genotype 2 was characterized by the
      presence of strains belonging to 11 different subtypes, including 5 that had
      never been characterized. Genotypes 1a, 1b, 3a, and 4a presented typical
      "epidemic" profiles, with a large number of isolates per subtype and short mean
      genetic distances between isolates. Type 2 isolates displayed a typical "endemic"
      profile, with a large number of subtypes and very few isolates in each subtype.
      The epidemiology of HCV infection in southeast France changed radically during
      the study period in relation to modifications in the etiology of infection. We
      observed the emergence of new epidemic subtypes (subtypes 1a and 3) linked to
      intravenous drug use and a decrease in the types linked to blood transfusion and
      nosocomial infection (epidemic subtype 1b and endemic type 2). Comparison of
      strains from blood donors with strains from a cohort of inpatients in the same
      region during 2001 and 2002 demonstrated for the first time that the monitoring
      of blood donors is a generally valid indicator of HCV epidemiology in terms of
      genotype distribution.

PMID- 16081889
TI  - Real-time quantitative PCR for determining the burden of Plasmodium falciparum
      parasites during pregnancy and infancy.
AB  - Real-time quantitative PCR (RTQ-PCR) provides a quick, accurate, and reproducible
      quantification of parasites. However, the value of RTQ-PCR for predicting
      clinical outcomes of malaria is unknown. Here, we compared RTQ-PCR to microscopy
      of blood smears, nested PCR (nPCR), and parasite circulating-antigen (CAg) assays
      for detection of Plasmodium falciparum in pregnant Kenyan women and their infants
      and related these findings to parity and birth weights in their newborns (n =
      554). nPCR was the most sensitive assay for detection of malaria in pregnancy,
      followed in decreasing order of sensitivity by RTQ-PCR, CAg assays, and blood
      smears. RTQ-PCR detected a higher frequency of malaria infection (46%) in
      maternal peripheral blood in primiparous than in multiparous women (35%; P <
      0.001), with a >12-fold difference in parasite burden (geometric mean = 25,870
      versus 2,143 amplicons/microl blood; P < 0.0001). Similarly, the presence of
      placental malaria determined by RTQ-PCR was approximately twofold higher in
      primiparous versus multiparous women (21% versus 13%; P < 0.01). The presence and
      intensity of malaria infection in pregnant women estimated by RTQ-PCR strongly
      correlated with low-birth-weight babies, especially in those with high amplicon
      numbers. RTQ-PCR identified malaria-infected women, missed by blood smear, who
      were at risk for having underweight offspring. By contrast, malaria detected by
      nPCR and CAg assay showed a much weaker association with parity or low birth
      weight. Thus, RTQ-PCR provides an estimate of parasite burden that is more
      sensitive than blood smear and is predictive of clinical outcomes of malaria
      infection in pregnant women and newborns.

PMID- 16081890
TI  - Etiology of diarrhea in young children in Denmark: a case-control study.
AB  - Infectious gastroenteritis is one of the most common diseases in young children.
      To clarify the infectious etiology of diarrhea in Danish children less than 5
      years of age, we conducted a 2-year prospective case-control study. Stools from
      424 children with diarrhea and 870 asymptomatic age-matched controls were
      examined, and their parents were interviewed concerning symptoms. Rotavirus,
      adenovirus, and astrovirus were detected by enzyme-linked immunosorbent assay,
      and norovirus and sapovirus were detected by PCR. Salmonella, thermotolerant
      Campylobacter, Yersinia, Shigella, and Vibrio spp. were detected by standard
      methods. Shiga toxin-producing (STEC), attaching-and-effacing (A/EEC),
      enteropathogenic (EPEC), enterotoxigenic, enteroinvasive, and enteroaggregative
      Escherichia coli were detected by using colony hybridization with virulence gene
      probes and serotyping. Parasites were detected by microscopy. Overall, a
      potential pathogen was found in 54% of cases. More cases than controls were
      infected with rotavirus, Salmonella, norovirus, adenovirus, Campylobacter,
      sapovirus, STEC, classical EPEC, Yersinia, and Cryptosporidium strains, whereas
      A/EEC, although common, was not associated with illness. The single most
      important cause of diarrhea was rotavirus, which points toward the need for a
      childhood vaccine for this pathogen, but norovirus, adenovirus, and sapovirus
      were also major etiologies. Salmonella sp. was the most common bacterial
      pathogen, followed by Campylobacter, STEC, Yersinia, and classical EPEC strains.
      A/EEC not belonging to the classical EPEC serotypes was not associated with
      diarrhea, underscoring the importance of serotyping for the definition of EPEC.

PMID- 16081891
TI  - First nosocomial outbreak of vancomycin-resistant Enterococcus faecium expressing
      a VanD-like phenotype associated with a vanA genotype.
AB  - Although enterococci expressing acquired vancomycin resistance phenotype have
      been reported increasingly worldwide, they have been rarely reported in France.
      From August to December 2004 we faced an outbreak of vancomycin-resistant
      Enterococcus faecium (VRE) isolates in the nephrology department at Bicetre
      Hospital (K.-Bicetre, France). The expression of the glycopeptide resistance
      varied among the 26 VRE isolates, with vancomycin MICs ranging from 12 to >256
      microg/ml, whereas teicoplanin MICs ranged from 4 to 48 microg/ml. However,
      several strains appeared to be susceptible to glycopeptides according to disk
      diffusion testing and expressed resistance only after subculture with
      glycopeptides. In addition, a heterogeneous expression of glycopeptide resistance
      was also observed. This so-called VanD-like phenotype of resistance (low-level
      resistance to vancomycin and mostly susceptibility to teicoplanin) was
      surprisingly associated with a vanA gene. Plasmid extraction and mating-out
      experiments indicated that the vanA gene was located on a 200-kb self
      transferable plasmid. Pulsed-field gel electrophoresis identified mostly
      dissemination of a single clone, whereas diffusion of the VanA-positive plasmid
      in different genomic backgrounds had also occurred. The vanA gene was part of a
      vanA-type operon for expression of resistance located on a Tn1546-like
      transposon. Sequencing of this transposon identified insertion of insertion
      sequence IS16 in the vanY gene that encodes a d,d-carboxypeptidase that might
      explain in part the peculiar VanD-type phenotype of resistance. This report is
      the first description of a VRE outbreak in France and underlines the difficulty
      in detecting this organism due to variability on the expression of the
      glycopeptide resistance trait, if any.

PMID- 16081892
TI  - Sensitivity of PCR targeting the IS2404 insertion sequence of Mycobacterium
      ulcerans in an Assay using punch biopsy specimens for diagnosis of Buruli ulcer.
AB  - Punch biopsy specimens from Mycobacterium ulcerans disease lesions were used to
      compare the sensitivities and specificities of direct smear, culture, PCR, and
      histopathology in making a diagnosis of M. ulcerans disease in a field setting.
      PCR for the insertion element IS2404 was modified to include uracil-N-glycosylase
      and deoxyuridine triphosphate instead of deoxythymidine triphosphate to reduce
      the risk of cross contamination. The "gold standard" for confirmation of
      clinically diagnosed Buruli ulcer was a definite histological diagnosis, a
      positive culture for M. ulcerans, or a smear positive for acid-fast bacilli
      (AFB), together with a possible histological diagnosis. For 70 clinically
      diagnosed cases of M. ulcerans disease, the modified PCR was 98% sensitive and
      gave a rapid result. The sensitivities of microscopy, culture, and histology were
      42%, 49%, and 82%, respectively. The use of a 4-mm punch biopsy specimen was
      preferred to a 6-mm punch biopsy specimen since the wound was less likely to
      bleed and to need stitching. Given adequate technical expertise and the use of
      controls, the PCR was viable in a teaching hospital setting in Ghana; and in
      routine practice, we would recommend the use of Ziehl-Neelsen staining of biopsy
      specimens to detect AFB, followed by PCR, in AFB-negative cases only, in order to
      minimize costs. Histology and culture remain important as quality control tests,
      particularly in studies of treatment efficacy.

PMID- 16081893
TI  - Molecular model for studying the uncultivated fungal pathogen Lacazia loboi.
AB  - Lacazia loboi is an uncultivated fungal pathogen of humans and dolphins that
      causes cutaneous and subcutaneous infections only in the tropical areas of the
      Americas. It was recently found by phylogenetic analysis that this unusual
      pathogen is closely related to Paracoccidioides brasiliensis and to the other
      fungal dimorphic members of the order Onygenales. That original phylogenetic
      study used universal primers to amplify well-known genes. However, this approach
      cannot be applied to the study of other proteins. We have developed a strategy
      for studying the gene encoding the gp43 homologous protein of P. brasiliensis in
      L. loboi. The gp43 protein was selected because it has been found that this P.
      brasiliensis antigen strongly reacts when it is used to test sera from patients
      with lacaziosis. The principle behind this idea was to obtain the gp43 amino acid
      sequence of P. brasiliensis and other homologous fungal sequences from GenBank
      and design primers from their aligned conserved regions. These sets of primers
      were used to amplify the selected regions with genomic DNA extracted from the
      yeast-like cells of L. loboi from experimentally infected mice. Using this
      approach, we amplified 483 bp of the L. loboi gp43-like gene. These sequences had
      85% identity at the nucleotide level and 75% identity with the deduced amino acid
      sequences of the P. brasiliensis gp43 protein. The identity of the 483-bp DNA
      fragment was confirmed by phylogenetic analysis. This analysis revealed that the
      L. loboi gp43-like deduced amino acid sequence formed a strongly supported (100%)
      sister group with several P. brasiliensis gp43 sequences and that this taxon in
      turn was linked to the other fungal sequences used in this analysis. This study
      shows that the use of a molecular model for investigation of the genes encoding
      important proteins in L. loboi is feasible.

PMID- 16081894
TI  - Use of a suspension array for rapid identification of the varieties and genotypes
      of the Cryptococcus neoformans species complex.
AB  - Cryptococcus neoformans is an encapsulated fungal pathogen known to cause severe
      disease in immunocompromised patients. The disease, cryptococcosis, is mostly
      acquired by inhalation and can result in a chronic meningoencephalitis, which can
      be fatal. Here, we describe a molecular method to identify the varieties and
      genotypic groups within the C. neoformans species complex from culture-based
      assays. The method employs a novel flow cytometer with a dual laser system that
      allows the simultaneous detection of different target sequences in a multiplex
      and high-throughput format. The assay uses a liquid suspension hybridization
      format with specific oligonucleotide probes that are covalently bound to the
      surface of fluorescent color-coded microspheres. Biotinylated target amplicons,
      which hybridized to their complementary probe sequences, are quantified by the
      addition of the conjugate, streptavidin R-phycoerythrin. In this study we
      developed and validated eight probes derived from sequence analysis of the
      intergenic spacer region of the rRNA gene region. The assay proved to be specific
      and sensitive, allowed discrimination of a 1-bp mismatch with no apparent cross
      reactivity, and detected 10(1) to 10(3) genome copies. The described protocol,
      which can be used directly with yeast cells or isolated DNA, can be undertaken in
      less than 1 h following PCR amplification and permits identification of species
      in a multiplex format. In addition to a multiplex capability, the assay allows
      the simultaneous detection of target sequences in a single reaction. The
      accuracy, speed, flexibility, and sensitivity of this technology are a few of the
      advantages that will make this assay useful for the diagnosis of human
      cryptococcal infections and other pathogenic diseases.

PMID- 16081895
TI  - Development of a new oligonucleotide array to identify staphylococcal strains at
      species level.
AB  - The genus Staphylococcus is made up of 36 validated species which contain strains
      that are pathogenic, saprophytic, or used as starter cultures for the food
      industry. An oligonucleotide array targeting the manganese-dependent superoxide
      dismutase (sodA) gene was developed to overcome the drawbacks of the conventional
      methods of identification. Divergences of the sodA gene were used to design
      oligonucleotide probes, and we showed that each of the 36 species had a
      characteristic pattern of hybridization. To evaluate the array, we analyzed 38
      clinical and 38 food or food plant Staphylococcus isolates identified by the
      phenotype-based system VITEK 2 (bioMerieux). This commercial kit failed to
      identify 8 (21%) of the clinical isolates and 32 (84%) of the food and food plant
      isolates. In contrast, the oligonucleotide array we designed provided an accurate
      and rapid method for the identification of staphylococcal strains, isolated from
      clinical, environmental, or food samples, at species level.

PMID- 16081896
TI  - Strain variation among Bordetella pertussis isolates in finland, where the whole
      cell pertussis vaccine has been used for 50 years.
AB  - Pertussis is an infectious disease of the respiratory tract caused by Bordetella
      pertussis. Despite the introduction of mass vaccination against pertussis in
      Finland in 1952, pertussis has remained an endemic disease with regular
      epidemics. To monitor changes in the Finnish B. pertussis population, 101
      isolates selected from 1991 to 2003 and 21 isolates selected from 1953 to 1982
      were studied together with two Finnish vaccine strains. The analyses included
      serotyping of fimbriae (Fim), genotyping of the pertussis toxin S1 subunit (ptxA)
      and pertactin (prn), and pulsed-field gel electrophoresis (PFGE) after digestion
      of B. pertussis genomic DNA with XbaI restriction enzyme. Strains isolated before
      1977 were found to harbor the same ptxA as the strains used in the Finnish whole
      cell pertussis vaccine, and strains isolated before 1982 harbored the same prn as
      the strains used in the Finnish whole-cell pertussis vaccine. All recent
      isolates, however, represented genotypes distinct from those of the two vaccine
      strains. A marked shift of predominant serotype from Fim serotype 2 (Fim2) to
      Fim3 has been observed since the late 1990s. Temporal changes were seen in the
      genome of B. pertussis by PFGE analysis. Three PFGE profiles (BpSR1, BpSR11, and
      BpSR147) were distinguished by their prevalence between 1991 and 2003. The yearly
      emergence of the three profiles was distributed periodically. Our study stresses
      the importance of the continuous monitoring of emerging strains of B. pertussis
      and the need to obtain a better understanding of the relationship of the
      evolution of B. pertussis in vaccinated populations.

PMID- 16081897
TI  - DNA sequence-based subtyping and evolutionary analysis of selected Salmonella
      enterica serotypes.
AB  - While serotyping and phage typing have been used widely to characterize
      Salmonella isolates, sensitive subtyping methods that allow for evolutionary
      analyses are essential for examining Salmonella transmission, ecology, and
      evolution. A set of 25 Salmonella enterica isolates, representing five clinically
      relevant serotypes (serotypes Agona, Heidelberg, Schwarzengrund, Typhimurium, and
      Typhimurium var. Copenhagen) was initially used to develop a multilocus sequence
      typing (MLST) scheme for Salmonella targeting seven housekeeping and virulence
      genes (panB, fimA, aceK, mdh, icdA, manB, and spaN). A total of eight MLST types
      were found among the 25 isolates sequenced. A good correlation between MLST types
      and Salmonella serotypes was observed; only one serotype Typhimurium var.
      Copenhagen isolate displayed an MLST type otherwise typical for serotype
      Typhimurium isolates. Since manB, fimA, and mdh allowed for the highest subtype
      discrimination among the initial 25 isolates, we chose these three genes to
      perform DNA sequencing of an additional 41 Salmonella isolates representing a
      larger diversity of serotypes. This "three-gene sequence typing scheme" allowed
      discrimination of 25 sequence types (STs) among a total of 66 isolates; STs
      correlated well with serotypes and allowed within-serotype differentiation for 9
      of the 12 serotypes characterized. Phylogenetic analyses showed that serotypes
      Kentucky and Newport could each be separated into two distinct, statistically
      well supported evolutionary lineages. Our results show that a three-gene sequence
      typing scheme allows for accurate serotype prediction and for limited subtype
      discrimination among clinically relevant serotypes of Salmonella. Three-gene
      sequence typing also supports the notion that Salmonella serotypes represent both
      monophyletic and polyphyletic lineages.

PMID- 16081898
TI  - Use of the genotype MTBDR assay for rapid detection of rifampin and isoniazid
      resistance in Mycobacterium tuberculosis complex isolates.
AB  - A commercially available DNA strip assay (Genotype MTBDR; Hain Lifescience,
      Nehren, Germany) was evaluated for its ability to detect mutations conferring
      resistance to rifampin (RMP) and isoniazid (INH) in clinical Mycobacterium
      tuberculosis complex isolates. A total of 103 multidrug-resistant (MDR; i.e., at
      least resistant to RMP and INH) and 40 fully susceptible strains isolated in
      Germany in 2001 in which resistance mutations have been previously defined by DNA
      sequencing and real-time PCR analysis were investigated. The Genotype MTBDR assay
      identified 102 of the 103 MDR strains with mutations in the rpoB gene (99%) and
      91 strains (88.4%) with mutations in codon 315 of katG. All 40 susceptible
      strains showed a wild-type MTBDR hybridization pattern. The concordance between
      the MTBDR assay and the DNA sequencing results was 100%. Compared to conventional
      drug susceptibility testing, the sensitivity and specificity were 99 and 100% for
      RMP resistance and 88.4 and 100% for INH resistance, respectively. In conclusion,
      the MTBDR assay is a rapid and easy-to-perform test for the detection of the most
      common mutations found in MDR M. tuberculosis strains that can readily be
      included in a routine laboratory work flow.

PMID- 16081899
TI  - Genomic polymorphisms for Mycobacterium avium subsp. paratuberculosis
      diagnostics.
AB  - Mycobacterium avium subsp. paratuberculosis is an emerging pathogen of mammals
      and is being actively investigated as a possible zoonotic agent. The lack of
      reliable diagnostic assays has hampered rational assessment of the prevalence of
      this organism in humans and animals. We have used a comparative genomic approach
      to reveal genomic differences between M. avium subsp. paratuberculosis and its
      close relative M. avium subsp. avium, a highly prevalent environmental organism.
      From computational and DNA microarray-based study of two prototype strains, M.
      avium subsp. avium strain 104 and M. avium subsp. paratuberculosis strain K10, we
      have uncovered two types of large sequence polymorphisms (LSPs): those present in
      the former but missing in the latter (LSP(A)s) and those only present in the
      latter (LSP(P)s). We examined the distribution of 3 LSP(A)s and 17 LSP(P)s across
      a panel of 383 M. avium complex isolates in order to determine their potential
      utility for the development of accurate diagnostic tests. Our results show that
      the absence of LSP(A)8 is 100% specific for the identification of M. avium subsp.
      paratuberculosis. Of the 17 LSP(P)s, 10 regions were not specific for M. avium
      subsp. paratuberculosis while 7 were shown to be highly specific (>98%) and, in
      some cases, highly sensitive as well (up to 95%). These data highlight the need
      to evaluate these regions across a diverse panel of clinical and environmental
      isolates and indicate the LSPs best suited for M. avium subsp. paratuberculosis
      diagnostics.

PMID- 16081900
TI  - Corynebacterium resistens sp. nov., a new multidrug-resistant coryneform
      bacterium isolated from human infections.
AB  - Five strains of an unknown, multidrug-resistant coryneform, gram-positive rod
      were isolated from blood, bronchial aspirate, and abscess specimens. Four of the
      five strains isolated were highly resistant to antimicrobial agents, including
      beta-lactams, aminoglycosides, macrolides, quinolones, and tetracyclines, except
      for glycopeptides. In immunocompromised patients, bacteremia associated with this
      organism was rapidly fatal. This coryneform bacterium was nonmotile, lipophilic,
      and nonsaccharolytic. Lack of pyrazinamidase activity differentiated this
      organism from other lipophilic corynebacteria. Chemotaxonomic studies indicated
      that this multidrug-resistant coryneform bacterium belongs to the genus
      Corynebacterium. Comparative 16S rRNA gene sequencing and DNA-DNA hybridization
      analyses revealed that the five isolates were genetically identical and that they
      represent a new subline within the genus Corynebacterium, for which we propose
      the designation Corynebacterium resistens sp. nov. The type strain of
      Corynebacterium resistens is GTC 2026T (SICGH 158T, JCM 12819T, CCUG 50093T).

PMID- 16081901
TI  - Identification of immunodominant epitopes on the membrane protein of the severe
      acute respiratory syndrome-associated coronavirus.
AB  - Similar to other coronaviruses, the membrane (M) protein of severe acute
      respiratory syndrome-associated coronavirus (SARS-CoV) is a major transmembrane
      glycoprotein with multiple biological functions. To date, limited information is
      available about its antigenic properties. In this study, we identified two major
      immunodominant epitopes on the M protein located in the extreme N-terminal region
      (residues 1 to 31) and the interior C-terminal region (residues 132 to 161),
      respectively, by Pepscan analyses against convalescent-phase sera from SARS
      patients and antisera from virus-immunized mice and rabbits. Synthetic peptides
      M1-31 derived from the N-terminal epitope and M132-161 derived from the C
      terminal epitope were highly reactive with all of the convalescent-phase sera
      from 40 SARS patients but not with 30 control serum samples from healthy blood
      donors, suggesting their potential application for serologic diagnosis of SARS.
      We showed that both peptides (M1-31 and M132-161) were able to induce high titers
      of antibody responses in the immunized rabbits, highlighting their antigenicity
      and immunogenicity. These findings provide important information for developing
      SARS diagnostics and vaccines.

PMID- 16081902
TI  - Multilocus sequence typing of Swedish invasive group B streptococcus isolates
      indicates a neonatally associated genetic lineage and capsule switching.
AB  - Streptococcus agalactiae, also designated group B streptococcus (GBS), is an
      important pathogen in neonates, pregnant women, and nonpregnant adults with
      predisposing conditions. We used multilocus sequence typing (MLST) to
      characterize 158 GBS isolates that were associated with neonatal and adult
      invasive disease and that were collected in northern and western Sweden from 1988
      to 1997. Five major genetic lineages (sequence type [ST] 19, ST-17, ST-1, ST-23,
      and ST-9 complexes) were identified among the isolates, including serotype Ia,
      Ib, and II to V isolates, indicating a highly clonal population structure among
      invasive GBS isolates. A number of STs were found to contain isolates of
      different serotypes, which indicates that capsule switching occurred rather
      frequently. Two distantly related genetic lineages were identified among isolates
      of serotype III, namely, clonal complex 19 (CC19), and CC17. CC19 was equally
      common among isolates from adult and neonatal disease (accounting for 10.3% of
      GBS isolates from adult disease and 18.7% from neonatal disease), whereas CC17
      significantly appeared to be associated with neonatal invasive disease (isolated
      from 21.9% of neonatal isolates but only 2.6% of adult isolates). The
      distribution of the mobile elements GBSi1 and IS1548 reveals that they can act as
      genetic markers for lineages CC17 and CC19, respectively.

PMID- 16081903
TI  - High level of sequence diversity in the 16S rRNA genes of Haemophilus influenzae
      isolates is useful for molecular subtyping.
AB  - A molecular typing method based on the 16S rRNA sequence diversity was developed
      for Haemophilus influenzae isolates. A total of 330 H. influenzae isolates were
      analyzed, representing a diverse collection of U.S. isolates. We found a high
      level of 16S rRNA sequence heterogeneity (up to 2.73%) and observed an exclusive
      correlation between 16S types and serotypes (a to f); no 16S type was found in
      more than one serotype. Similarly, no multilocus sequence typing (MLST) sequence
      type (ST) was found in more than one serotype. Our 16S typing and MLST results
      are in agreement with those of previous studies showing that serotypable H.
      influenzae isolates behave as highly clonal populations and emphasize the lack of
      clonality of nontypable (NT) H. influenzae isolates. There was not a 1:1
      correlation between 16S types and STs, but all H. influenzae serotypable isolates
      clustered similarly. This correlation was not observed for NT H. influenzae; the
      two methods clustered NT H. influenzae isolates differently. 16S rRNA gene
      sequencing alone provides a level of discrimination similar to that obtained with
      the analysis of seven genes for MLST. We demonstrated that 16S typing is an
      additional and complementary approach to MLST, particularly for NT H. influenzae
      isolates, and is potentially useful for outbreak investigation.

PMID- 16081904
TI  - Molecular subtyping of Treponema pallidum from North and South Carolina.
AB  - Patients from five clinics in North and South Carolina who had lesions suggestive
      of primary or secondary syphilis were evaluated using molecular techniques that
      allow the differentiation of Treponema pallidum strains on the basis of two
      variable genes, tpr and arp. Lesion samples were screened for the presence of T.
      pallidum DNA using PCR for polA, which represents a segment of the polymerase I
      gene that is unique to the spirochete. Twenty-seven of 154 lesion samples were
      found to contain T. pallidum, 23 of which had typeable DNA. Seven molecular
      subtypes were found (10f, 12f, 13f, 14f, 14g, 15f, and 16f); one to four subtypes
      were identified at each clinic. Subtype 14f was found in 52% of the typeable
      specimens and was distributed in four of the five clinics. Subtype 16f was found
      in 22% of specimens and was concentrated at one clinic. Further data are needed
      to define the role of this technique in examining the epidemiology of syphilis.

PMID- 16081905
TI  - Molecular detection method for all known genotypes of TT virus (TTV) and TTV-like
      viruses in thalassemia patients and healthy individuals.

PMID- 16081906
TI  - Ability of the vector tick Boophilus microplus to acquire and transmit Babesia
      equi following feeding on chronically infected horses with low-level parasitemia.
AB  - The protozoan parasite Babesia equi replicates within erythrocytes. During the
      acute phase of infection, B. equi can reach high levels of parasitemia, resulting
      in a hemolytic crisis. Horses that recover from the acute phase of the disease
      remain chronically infected. Subsequent transmission is dependent upon the
      ability of vector ticks to acquire B. equi and, following development and
      replication, establishment of B. equi in the salivary glands. Although
      restriction of the movement of chronically infected horses with B. equi is based
      on the presumption that ticks can acquire and transmit the parasite at low levels
      of long-term infection, parasitemia levels during the chronic phase of infection
      have never been quantified, nor has transmission been demonstrated. To address
      these epidemiologically significant questions, we established long-term B. equi
      infections (>1 year), measured parasitemia levels over time, and tested whether
      nymphal Boophilus microplus ticks could acquire and, after molting to the adult
      stage, transmit B. equi to naive horses. B. equi levels during the chronic phase
      of infection ranged from 10(3.3) to 10(6.0)/ml of blood, with fluctuation over
      time within individual horses. B. microplus ticks fed on chronically infected
      horses with mean parasite levels of 10(5.5) +/- 10(0.48)/ml of blood acquired B.
      equi, with detection of B. equi in the salivary glands of 7 to 50% of fed ticks,
      a range encompassing the percentage of positive ticks that had been identically
      fed on a horse in the acute phase of infection with high parasitemia levels.
      Ticks that acquired B. equi from chronically infected horses, as well as those
      fed during the acute phase of infection, successfully transmitted the parasite to
      naive horses. The results unequivocally demonstrated that chronically infected
      horses with low-level parasitemia are competent mammalian reservoirs for tick
      transmission of B. equi.

PMID- 16081907
TI  - Identification of medically important molds by an oligonucleotide array.
AB  - Infections caused by fungi have increased in recent years. Accurate and rapid
      identification of fungal pathogens is important for appropriate treatment with
      antifungal agents. On the basis of the internal transcribed spacer 1 (ITS 1) and
      ITS 2 sequences of the rRNA genes, an oligonucleotide array was developed to
      identify 64 species (32 genera) of clinically important filamentous (or
      dimorphic) fungi. These 64 species included fungi causing superficial, cutaneous,
      subcutaneous, and invasive infections. The method consisted of PCR amplification
      of the ITS regions using a pair of universal primers, followed by hybridization
      of the digoxigenin-labeled PCR products to a panel of species- or group-specific
      oligonucleotides immobilized on a nylon membrane. Of 397 fungal strains (290
      target and 107 nontarget strains) tested, the sensitivity and specificity of the
      array was 98.3% (285/290) and 98.1% (105/107), respectively. Misidentified
      strains were usually those belonging to the same genus of the target species or
      having partial homology with oligonucleotide probes on the membrane. The whole
      procedure can be finished within 24 h starting from isolated colonies;
      reproductive structures, which are essential for the conventional identification
      methods, are not needed. In conclusion, the present array is a powerful tool for
      identification of clinically important filamentous fungi and may have the
      potential to be continually extended by adding further oligonucleotides to the
      array without significantly increasing the cost or complexity.

PMID- 16081908
TI  - Evaluation of the VACUTAINER PPT Plasma Preparation Tube for use with the Bayer
      VERSANT assay for quantification of human immunodeficiency virus type 1 RNA.
AB  - Separation and storage of plasma within 2 h of phlebotomy is required for the
      VACUTAINER PPT Plasma Preparation Tube (PPT) versus 4 h for the predecessor
      VACUTAINER EDTA tube for human immunodeficiency virus type 1 (HIV-1) viral load
      (HIVL) testing by the VERSANT HIV-1 RNA 3.0 assay (branched DNA). The 2-h limit
      for PPT imposes time constraints for handling and transporting to the testing
      laboratory. This study compares HIVL reproducibility from matched blood in EDTA
      tubes and PPTs and between PPT pairs following processing within 4 h of
      phlebotomy, stability of plasma HIV-1 RNA at 24- and 72-h room temperature
      storage in the tube, and comparative labor and supply requirements. Blood from
      159 patients was collected in paired tubes (EDTA/PPT or PPT/PPT): 86 paired EDTA
      tubes and PPTs were processed 4 h following phlebotomy and their HIVLs were
      compared, 42 paired PPT/PPT pairs were analyzed for intertube HIVL
      reproducibility, and 31 PPT/PPT pairs were analyzed for HIV-1 RNA stability by
      HIVL. Labor and supply requirements were compared between PPT and EDTA tubes.
      PPTs produce results equivalent to standard EDTA tube results when processed 4 h
      after phlebotomy. PPT intertube analyte results are reproducible. An average
      decrease of 13% and 37% in HIVL was observed in PPT plasma after 24 and 72 h of
      room temperature storage, respectively; thus, plasma can be stored at room
      temperature up to 24 h in the original tube. PPTs offer labor and supply savings
      over EDTA tubes.

PMID- 16081909
TI  - Broadly reactive nested reverse transcription-PCR using an internal RNA standard
      control for detection of noroviruses in stool samples.
AB  - We developed a nested reverse transcription-PCR (nRT-PCR) for the detection of
      noroviruses in stools, using random primers for RT, the JV12/JV13 primer pair in
      the first round of nPCR, and a set of nine inner primers for the second,
      comprising the reverse sequences of primers SR46, SR48, SR50, and SR52, and five
      novel oligonucleotide sequences (113-1, 113-2, 115-1, 115-2, and 115-3). The
      specificity of the nRT-PCR was confirmed by testing 61 stools containing enteric
      viruses other than noroviruses. In comparative assays on either stools or RNA
      dilutions from two genogroup I and three genogroup II (GII) norovirus-positive
      samples, nRT-PCR was always at least as sensitive as RT-PCR and Southern
      hybridization. With some of the samples tested, the increase in sensitivity was
      10-fold or higher. For GII viruses, the detectable range of nRT-PCR was estimated
      to be 8.4 x 10(4) to 2 RNA viral particles. When used on 85 stools from pediatric
      patients with acute gastroenteritis negative for viruses by electron microscopy
      and cell culture, the nRT-PCR detected norovirus in 19 samples (22.3%), while it
      failed to detect one reference RT-PCR-positive sample containing a Desert Shield
      strain. Sixteen of the 19 nRT-PCR-positive samples gave concordant results with
      reference RT-PCR and Southern hybridization, and all with sequence analysis.
      Partial sequencing of the polymerase region revealed that from January to April
      2000 all GII strains except two (Rotterdam- and Leeds-like viruses) formed a
      tight cluster related to Hawaii virus. The nRT-PCR described could prove suitable
      for large epidemiological studies and for specialized clinical laboratories
      performing routine molecular testing.

PMID- 16081910
TI  - DNA probe array for the simultaneous identification of herpesviruses,
      enteroviruses, and flaviviruses.
AB  - Viral infections of the central nervous system (CNS) are caused by a variety of
      viruses, namely, herpesviruses, enteroviruses, and flaviviruses. The similar
      clinical signs provoked by these viruses make the diagnosis difficult. We report
      on the simultaneous detection of these major CNS pathogens using amplification by
      PCR and detection of amplified products using DNA microarray technology.
      Consensus primers were used for the amplification of all members of each genus.
      Sequences specific for the identification of each virus species were selected
      from the sequence alignments of each target gene and were synthesized on a high
      density microarray. The amplified products were pooled, labeled, and cleaved,
      followed by hybridization on a single array. This method was successfully used to
      identify herpesviruses, namely, herpes simplex virus type 1 (HSV-1), HSV-2, and
      cytomegalovirus; all serotypes of human enteroviruses; and five flaviviruses
      (West Nile virus, dengue viruses, and Langat virus). This approach, which used
      highly conserved consensus primers for amplification and specific sequences for
      identification, would be extremely useful for the detection of variants and would
      probably help solve some unexplained cases of encephalitis. The analytical
      sensitivity of the method was shown to be 500 genome equivalents ml(-1) for HSV
      1, 0.3 50% tissue culture infectious doses (TCID50s) ml(-1) for the enterovirus
      coxsackievirus A9, and 200 TCID50s ml(-1) for West Nile virus. The clinical
      sensitivity of this method must now be evaluated.

PMID- 16081911
TI  - Use of fluorescent probes to determine MICs of amphotericin B and caspofungin
      against Candida spp. and Aspergillus spp.
AB  - We investigated the utility of mechanism-based fluorescent probes for
      determination of MICs (FMICs) of amphotericin B and caspofungin against Candida
      spp. and Aspergillus spp. Amphotericin B was selected as a membrane-active
      antifungal agent, and caspofungin was selected as a cell wall-active agent. FMICs
      were also compared to the MIC determined by CLSI (formerly NCCLS) methods. Five
      isolates per species of Candida albicans, Candida glabrata, Candida parapsilosis,
      Aspergillus fumigatus, and Aspergillus terreus were studied with either
      amphotericin B or caspofungin. The fluorescent probes, carboxyfluorescein
      diacetate (CFDA) for cytoplasmic esterase activity and dihexyloxacarbocyanine
      iodide (DiOC6) for cell membrane potential, were each added to their respective
      plates. MICs and FMICs were determined in at least three separate experiments (in
      duplicate). Fluorescence was measured using a 96-well plate fluorometer. For
      amphotericin B and caspofungin, the FMIC end point was the lowest concentration
      of drug at which the percent growth inhibition from treated organisms versus
      control organisms displayed 80% inhibition for amphotericin B and 50% inhibition
      for caspofungin as measured by a fluorescent signal. The MIC for amphotericin B
      was defined as the lowest concentration of antifungal displaying no visible
      growth for both Aspergillus and Candida spp. The MIC for caspofungin was the
      lowest concentration of drug that displayed a minimum effective concentration for
      Aspergillus spp. For Candida spp., the MIC for caspofungin was defined as the
      concentration at which the antifungal agent significantly inhibits the organism.
      The FMICs of both antifungals, as measured by the DiOC6 membrane probe, showed
      good agreement (83% to 100%), within one well dilution, with the MICs against
      amphotericin B and caspofungin for all species. Also, the FMICs measured by the
      CFDA cytoplasmic esterase probe reflecting damage due to cell wall or cell
      membrane showed strong agreement (79 to 100%) with the MICs of both amphotericin
      B and caspofungin for all species. There was no significant difference in
      comparisons of MIC and FMIC values (P > or = 0.05). The use of fluorescent probes
      provides a mechanism-based method of determination of MICs of amphotericin B and
      caspofungin against Candida spp. and Aspergillus spp. that correlates well with
      standard methods.

PMID- 16081912
TI  - Human immunodeficiency virus (HIV) reverse transcriptase activity correlates with
      HIV RNA load: implications for resource-limited settings.
AB  - Measurement of human immunodeficiency virus type 1 (HIV-1) plasma RNA levels
      using Roche AMPLICOR version 1.5 (HIV RNA) is an integral part of monitoring HIV
      infected patients in industrialized countries. These assays are currently
      unaffordable in resource-limited settings. We investigated a reverse
      transcriptase (RT) assay as a less expensive alternative for measuring viral
      burden that quantifies RT enzyme activity in clinical plasma samples. A
      comparison of RT and HIV RNA assays was performed on 29 paired plasma samples
      from patients living in the United States and 21 paired plasma samples from
      patients living in Cameroon. RT levels correlated significantly with plasma HIV
      RNA viral loads in plasma from U.S. patients (r = 0.898; P < 0.001) and
      Cameroonian patients, a majority of whom were infected with HIV-1 clade type
      CRF02_AG (r = 0.669; P < 0.01). Among 32 samples with HIV viral load of >2,000
      copies/ml, 97% had detectable RT activity. One Cameroon sample had undetectable
      RNA viral load but detectable RT activity of 3 fg/ml. The RT assay is a simple
      and less expensive alternative to the HIV RNA assay. Field studies comparing
      these assays in resource-limited settings are warranted to assess the
      practicality and usefulness of this assay for monitoring HIV-infected patients on
      antiretroviral therapy.

PMID- 16081913
TI  - Mannitol salt agar-cefoxitin combination as a screening medium for methicillin
      resistant Staphylococcus aureus.
AB  - In disk diffusion tests, cefoxitin is now considered a better indicator than
      oxacillin for the presence of the mecA gene in Staphylococcus aureus. A logical
      extension of this work is the incorporation of cefoxitin into media selective for
      methicillin-resistant Staphylococcus aureus (MRSA). This paper describes the
      development and subsequent testing of mannitol salt agar containing 4 mg/liter
      cefoxitin with a unique collection of well-characterized MRSA strains, including
      low-level methicillin-resistant strains and an equal number of known mecA
      negative S. aureus strains. The agar supported the growth of 96.6% of the mecA
      positive strains in the collection and inhibited the growth of 100% of the mecA
      negative strains. These results suggest that selective media based on cefoxitin
      are superior to those based on oxacillin for the detection of MRSA.

PMID- 16081914
TI  - Diagnosis of cat scratch disease with detection of Bartonella henselae by PCR: a
      study of patients with lymph node enlargement.
AB  - Cat scratch disease (CSD) is mostly due to Bartonella henselae after inoculation
      of the organism through a skin injury. Since the causative bacteria cannot be
      easily cultured from human lymph node samples, the diagnosis usually relies on
      epidemiological, clinical, histological, and serological criteria (classical
      criteria). A study was performed to determine the diagnostic value of PCR
      analysis for the detection of B. henselae for the diagnosis of CSD and its place
      in the diagnostic strategy alongside the classical criteria. Over a 7-year
      period, lymph node biopsy specimens or cytopunctures from 70 patients were
      systematically tested by PCR for the presence of B. henselae DNA (htrA gene) in
      the Bacteriology Laboratory of the Hopitaux Universitaires de Strasbourg.
      Serological testing by an immunofluorescence assay for B. henselae antibodies was
      also performed for each patient, and clinical, epidemiological, and histological
      data were collected. The patients were then divided into two groups according to
      the number of positive diagnostic criteria for CSD: 29 patients with definite CSD
      (two or more classical criteria) and 15 patients with possible CSD (less than two
      classical criteria). The remaining 26 patients for whom another diagnosis was
      retained were used as a control group. Among all criteria, PCR analysis had the
      best specificity (100%). The PCR assay for B. henselae was positive for 22 (76%;
      95% confidence interval [CI95], 56.5 to 89.7%) of the 29 definite CSD patients
      and 3 (20%; CI95, 4.3 to 48.1%) of the 15 possible CSD patients. We then studied
      combinations of diagnostic criteria, including B. henselae PCR analysis. The best
      diagnostic performance was observed if at least two criteria were present among
      serologic, epidemiologic, histological, and molecular criteria.

PMID- 16081915
TI  - In vitro susceptibilities of clinical isolates of Candida species, Cryptococcus
      neoformans, and Aspergillus species to itraconazole: global survey of 9,359
      isolates tested by clinical and laboratory standards institute broth
      microdilution methods.
AB  - The in vitro activity of itraconazole was determined against 7,299 isolates of
      Candida spp., 1,615 isolates of Cryptococcus neoformans, and 445 isolates of
      Aspergillus spp. obtained from over 200 medical centers worldwide. Itraconazole
      was active against all Candida spp. (96% of MICs were < or =1 microg/ml) with the
      exception of C. glabrata (77% of MICs were < or =1 microg/ml). Itraconazole
      inhibited 94% of C. krusei and 84% of other fluconazole-resistant Candida
      species, exclusive of C. glabrata, at a MIC of < or =1 microg/ml. Itraconazole
      was not active against fluconazole-resistant isolates of C. glabrata. Only modest
      activity was seen against C. neoformans (80% of MICs were < or =1 microg/ml);
      however, itraconazole showed excellent activity against Aspergillus spp. (94% of
      MICs were < or =1 microg/ml). These results provide an update on the antifungal
      activity of itraconazole against major opportunistic fungal pathogens. In light
      of the new intravenous formulation of itraconazole these data suggest that this
      agent remains a viable systemically active antifungal agent.

PMID- 16081916
TI  - Computational approach involving use of the internal transcribed spacer 1 region
      for identification of Mycobacterium species.
AB  - The rapid and reliable identification of clinically significant Mycobacterium
      species is a challenge for diagnostic laboratories. This study evaluates a unique
      sequence-dependent identification algorithm called MycoAlign for the differential
      identification of Mycobacterium species. The MycoAlign system uses pan
      Mycobacterium-specific primer amplification in combination with a customized
      database and algorithm. The results of testing were compared with conventional
      phenotypic assays and GenBank sequence comparisons using the 16S rRNA target.
      Discrepant results were retested and evaluated using a third independent
      database. The custom database was generated using the hypervariable sequences of
      the internal transcribed spacer 1 (ITS-1) region of the rRNA gene complex from
      characterized Mycobacterium species. An automated sequence-validation process was
      used to control quality and specificity of evaluated sequence. A total of 181
      Mycobacterium strains (22 reference strains and 159 phenotypically identified
      clinical isolates) and seven nonmycobacterial clinical isolates were evaluated in
      a comparative study to validate the accuracy of the MycoAlign algorithm.
      MycoAlign correctly identified all referenced strains and matched species in 94%
      of the phenotypically identified Mycobacterium clinical isolates. The ITS-1
      sequence target showed a higher degree of specificity in terms of Mycobacterium
      identification than the 16S rRNA sequence by use of GenBank BLAST. This study
      showed the MycoAlign algorithm to be a reliable and rapid approach for the
      identification of Mycobacterium species and confirmed the superiority of the ITS
      1 region sequence over the 16S rRNA gene sequence as a target for sequence-based
      species identification.

PMID- 16081917
TI  - Results of disk diffusion testing with cefoxitin correlate with presence of mecA
      in Staphylococcus spp.
AB  - The cefoxitin disk diffusion (DD) test for predicting mecA-mediated oxacillin
      resistance in staphylococci was assessed during a three-phase study. In phase 1,
      one laboratory tested 62 and 53 strains of Staphylococcus aureus and coagulase
      negative staphylococci (CoNS), respectively. These data were used to choose the
      provisional cefoxitin DD breakpoints (resistant/susceptible) of < or =19 mm/> or
      =20 mm for S. aureus and < or =24 mm/> or =25 mm for CoNS for the next phase of
      testing. In phase 2, 10 laboratories each tested approximately 40 in-house
      strains of staphylococci (half of which were S. aureus) using Mueller-Hinton agar
      from different manufacturers. In this phase, the sensitivity and specificity,
      respectively, of the cefoxitin disk test were 98 and 100% for S. aureus and 99
      and 96% for CoNS. The cefoxitin DD test performed equivalently to oxacillin broth
      microdilution (BMD) and to oxacillin DD tests among S. aureus and mecA-positive
      CoNS strains but gave better results than oxacillin BMD or oxacillin DD for mecA
      negative strains of CoNS. The cefoxitin DD test also was much easier to read and
      did not require the use of transmitted light for detection of resistance. Based
      on data from the first two phases, the Clinical and Laboratory Standards
      Institute (CLSI; formerly NCCLS) adopted the use of the cefoxitin DD test for
      predicting mecA-mediated oxacillin resistance in staphylococci and revised Table
      2C in CLSI document M100-S14 to reflect the change. In the third phase, an
      additional 61 challenge strains of CoNS for which the oxacillin MICs were 0.5 to
      2 microg/ml were tested in a single laboratory to determine the effectiveness of
      the cefoxitin DD test for this group of borderline-resistant isolates. These data
      were used to refine the description of the test in CLSI document M100-S15. The
      cefoxitin DD test is preferred over the oxacillin DD test for predicting mecA
      mediated oxacillin resistance in S. aureus and CoNS.

PMID- 16081918
TI  - Nosocomial outbreak caused by multidrug-resistant Pseudomonas aeruginosa
      producing IMP-13 metallo-beta-lactamase.
AB  - An outbreak of Pseudomonas aeruginosa showing a multidrug-resistant (MDR)
      phenotype (including carbapenems, ceftazidime, cefepime, gentamicin, tobramycin,
      and fluoroquinolones) was observed, during a 5-month period, in a general
      intensive care unit of a large tertiary care and clinical research hospital in
      southern Italy. The outbreak involved 15 patients, with a total of 87 isolates,
      mostly from lower respiratory tract specimens. Analysis of isolates involved in
      the outbreak revealed production of metallo-beta-lactamase (MBL) activity, and
      genotyping by pulsed-field gel electrophoresis of genomic DNA digested by SpeI
      revealed clonal relatedness among isolates. Molecular analysis of the MBL
      determinant showed the presence of a bla(IMP-13) gene carried on a gene cassette
      inserted in a class 1 integron which also contained an aacA4 aminoglycoside
      resistance cassette encoding an AAC(6')-Ib enzyme. The bla(IMP-13)-containing
      integron and its genetic environment appeared to be similar to those found in P.
      aeruginosa isolates producing IMP-13 from a hospital in Rome. The bla(IMP-13)
      gene was not transferable by conjugation and was apparently carried on the
      chromosome. The outbreak was coincidental with a shortage of nursing personnel,
      and resolution was apparently associated with reinstatement of nursing personnel
      and reinforcement of general infection control practices within the intensive
      care unit. To our best knowledge this is the first description of a nosocomial
      outbreak of relatively large size caused by an IMP-producing gram-negative
      pathogen in Europe.

PMID- 16081919
TI  - Analysis of the comparative workflow and performance characteristics of the VITEK
      2 and Phoenix systems.
AB  - The VITEK 2 (bioMerieux, Marcy L'Etoile, France) and the Phoenix systems (BD
      Diagnostic Systems, Sparks, Md.) are automated instruments for rapid organism
      identification and susceptibility testing. We evaluated the workflow, the time to
      result, and the performance of identification and susceptibility testing of both
      instruments. A total of 307 fresh clinical isolates were tested: 141
      Enterobacteriaceae, 22 nonfermenters, 93 Staphylococcus spp., and 51 Enterococcus
      spp. Manipulation time was measured in batches, each with seven isolates, for a
      total of 39 batches. The mean (+/- standard deviation [SD]) manipulation time per
      batch was 20.9 +/- 1.8 min for Phoenix and 10.6 +/- 1.0 min for VITEK 2 (P <
      0.001). Mean (+/-SD) time to result for all bacterial groups was 727 +/- 162 min
      for Phoenix and 506 +/- 120 min for VITEK 2 (P < 0.001). Concerning
      identification, Phoenix and VITEK 2 yielded the same results for nonfermenters
      (100%), staphylococci (97%), and enterococci (100%). For 140 Enterobacteriaceae
      strains evaluated, 135 (96%) were correctly identified by Phoenix and 137 (98%)
      by VITEK 2 (P = 0.72). The overall category agreement for all isolates was 97.0%
      for both instruments. The minor error rate, major error rate, and very major
      error rate for all bacterial isolates tested were 3.0, 0.3, and 0.6 and 2.8, 0.2,
      and 1.7 for Phoenix and VITEK 2, respectively (P values of 0.76, 0.75, and 0.09).
      The VITEK 2 system required less manual manipulation time and less time than the
      Phoenix system to yield results.

PMID- 16081920
TI  - Genetic characteristics of human enterovirus 71 and coxsackievirus A16
      circulating from 1999 to 2004 in Shenzhen, People's Republic of China.
AB  - The genetic and phylogenetic characteristics of human enterovirus 71 (EV71) and
      coxsackievirus A16 (CA16) sampled from children with hand, foot, and mouth
      disease in Shenzhen, People's Republic of China, over a 6-year period (1999 to
      2004) were examined with reverse transcription-PCR and DNA sequencing. Out of 147
      stool specimens, 60 showed positive signals when screened with EV71- and CA16
      specific primers. EV71 was identified in 19 specimens, and CA16 was identified in
      41 specimens; coinfection by EV71 and CA16 was not observed. Phylogenetic
      analysis of all EV71 strains isolated from the mainland Chinese samples
      established C4 as the predominant genotype. Only one other known strain (3254-TAI
      98; AF286531), isolated in Taiwan in 1998, was identified as belonging to
      genotype C4. Phylogenetic analysis of CA16 strains allowed us to identify three
      new genetic lineages (A, B, and C), with lineage C recently predominating in
      Asian countries, such as the People's Republic of China, Malaysia, and Japan.
      These new observations indicate that CA16 circulating in the People's Republic of
      China is genetically diverse, and additional surveillance is warranted.

PMID- 16081921
TI  - Identification of four fimbria-encoding genomic islands that are highly specific
      for verocytotoxin-producing Escherichia coli serotype O157 strains.
AB  - Verocytotoxin-producing Escherichia coli causes zoonotic food- or waterborne
      infection that may be associated with massive outbreaks and with the serious
      complication of hemolytic uremic syndrome (HUS). Serotypes O157:H7 and O157:NM
      are more commonly associated with HUS and outbreaks than other serotypes, such as
      O26:H11. To determine whether a genetic basis exists for why serotype O157:H7/NM
      causes HUS and outbreaks more often than other serotypes, such as O26:H11, we
      conducted suppression subtractive hybridization (SSH) between the genomes of the
      sequenced O157:H7 strain EDL933 and CL1, a clinical serotype O26:H11 isolate.
      Genes from four EDL933 fimbria-encoding genomic O islands (OIs) (OI-1, -47, -141,
      and -154) were identified in the SSH library. OI-47 encodes several additional
      putative virulence factors, including secreted and signaling proteins, a
      hemolysin locus, a lipoprotein, an ABC transport system, and a lipid biosynthesis
      locus. The distribution of the OIs was investigated by PCR and Southern
      hybridization (when PCR was negative) with 69 VTEC strains belonging to 39
      different serotypes corresponding to 5 seropathotypes that differ in their
      disease and epidemic potential. The four OIs described here were distributed
      almost exclusively in serotypes O157:H7 and O157:NM, which indicates that they
      may be associated with the ability of these strains to colonize human and/or
      animal intestinal tracts and to cause epidemic and serious disease more
      frequently than other serotypes. The occurrence of the four OIs in
      enteropathogenic E. coli O55:H7 strains is consistent with their vertical
      inheritance by VTEC O157:H7/NM from this clonally related ancestor.

PMID- 16081922
TI  - Phylogenetic analysis of the spirochetes Borrelia parkeri and Borrelia turicatae
      and the potential for tick-borne relapsing fever in Florida.
AB  - Isolates of Borrelia turicatae, Borrelia parkeri, and the Florida canine borrelia
      (FCB) were examined to further phylogenetically characterize the identities of
      these spirochetes in the United States. DNA sequences of four chromosomal loci
      (the 16S rRNA gene, flaB, gyrB, and glpQ) were determined for eight isolates of
      B. turicatae and six isolates of B. parkeri, which grouped the spirochetes into
      two distinct but closely related taxa (>98% sequence identity) separate from
      Borrelia hermsii. The FCB was clearly separated with the group identified as B.
      turicatae, confirming this bacterium as a relapsing fever spirochete. Therefore,
      the potential for tick-borne relapsing fever in humans and other animals exists
      in Florida and future efforts are needed to determine the enzootic hosts and
      distribution of this spirochete in the southeastern United States. Analysis of
      plasmids demonstrated both linear and circular forms in B. turicatae but only
      linear plasmids in B. parkeri, which should be of interest to investigators
      concerned with plasmid diversity and evolution within this group of spirochetes.

PMID- 16081923
TI  - Impact of human immunodeficiency virus type 1 (HIV-1) genetic diversity on
      performance of four commercial viral load assays: LCx HIV RNA Quantitative,
      AMPLICOR HIV-1 MONITOR v1.5, VERSANT HIV-1 RNA 3.0, and NucliSens HIV-1 QT.
AB  - Human immunodeficiency virus type 1 (HIV-1) evolution and changing strain
      distribution present a challenge to nucleic acid-based assays. Reliable patient
      monitoring of viral loads requires the detection and accurate quantification of
      genetically diverse HIV-1. A panel of 97 HIV-1-seropositive plasma samples
      collected from Cameroon, Brazil, and South Africa was used to compare the
      performance of four commercially available HIV RNA quantitative tests: Abbott LCx
      HIV RNA Quantitative assay (LCx), Bayer Versant HIV-1 RNA 3.0 (bDNA), Roche
      AMPLICOR HIV-1 MONITOR v1.5 (Monitor v1.5), and bioMerieux NucliSens HIV-1 QT
      (NucliSens). The panel included group M, group O, and recombinant viruses based
      on sequence analysis of gag p24, pol integrase, and env gp41. The LCx HIV assay
      quantified viral RNA in 97 (100%) of the samples. In comparison, bDNA, Monitor
      v1.5, and NucliSens quantified viral RNA in 96.9%, 94.8%, and 88.6% of the
      samples, respectively. The two group O specimens were quantified only by the LCx
      HIV assay. Analysis of nucleotide mismatches at the primer/probe binding sites
      for Monitor v1.5, NucliSens, and LCx assays revealed that performance
      characteristics reflected differences in the level of genetic conservation within
      the target regions.

PMID- 16081924
TI  - New microsatellite multiplex PCR for Candida albicans strain typing reveals
      microevolutionary changes.
AB  - Five new microsatellite loci were described and characterized for use as
      molecular markers for the identification and genetic differentiation of Candida
      albicans strains. Following the typing of 72 unrelated clinical isolates, the
      analysis revealed that they were all polymorphic, presenting from 5 to 30 alleles
      and 8 to 46 different genotypes. The discriminatory power obtained by combining
      the information generated by three microsatellites used in a multiplex PCR
      amplification strategy was 0.99, the highest ever reported. The multiplex PCR was
      later used to test a total of 114 C. albicans strains, including multiple
      isolates from the same patient collected from different body locations and along
      episodes of vulvovaginal infections. Three different scenarios for strain
      relatedness were identified: (i) different isolates that were revealed to be the
      same strain, (ii) isolates that were the same strain but that apparently
      underwent a process of microevolution, and (iii) isolates that corresponded to
      different strains. Analysis of the microevolutionary changes between isolates
      from recurrent infections indicated that the genotype alterations observed could
      be the result of events that lead to the loss of heterozygosity (LOH). In one
      case of recurrent infection, LOH was observed at the CAI locus, and this could
      have been related to exposure to fluconazole, since such strains were exposed to
      this antifungal during treatment. The analysis of microsatellites by a multiplex
      PCR strategy was found to be a highly efficient tool for the rapid and accurate
      differentiation of C. albicans strains and adequate for the identification of
      fine microevolutionary events that could be related to strain microevolution in
      response to environmental stress conditions.

PMID- 16081925
TI  - Simultaneous detection of hepatitis C virus (HCV) core antigen and anti-HCV
      antibodies improves the early detection of HCV infection.
AB  - To evaluate whether a new enzyme immunoassay developed for the simultaneous
      detection of hepatitis C virus (HCV) core antigen (Ag) and anti-HCV antibodies
      (anti-HCV Ab) (Monolisa HCV Ag/Ab ULTRA; Bio-Rad) could improve the early
      detection of HCV infection, we compared its sensitivity to that of anti-HCV, HCV
      core Ag, and HCV RNA assays. The populations studied included 12 blood donor
      samples positive for HCV RNA and HCV core Ag but negative for anti-HCV antibodies
      and 23 hemodialysis patients who developed anti-HCV Ab (seroconversion) during
      the follow-up. From these 23 individuals, 83 samples sequentially collected prior
      to seroconversion and 108 samples collected after seroconversion were tested. Six
      of 12 blood donations were positive by the HCV Ag/Ab assay. In the hemodialysis
      cohort, the 24 HCV RNA-negative samples were negative by the HCV Ag/Ab assay and
      23 of the 59 HCV RNA-positive samples (39%) were positive. The HCV Ag/Ab assay
      detected HCV infection on average 21.6 days before the most sensitive antibody
      assay. The HCV Ag/Ab assay did not detect HCV infection as early as the HCV RNA
      assay (mean delay, 30.3 days) or HCV Ag assay (mean delays, 27.9, and 16.3 days
      by the HCV core Ag quantification assay and the HCV Ag blood screening assay,
      respectively). This new assay provides a notable improvement for the early
      detection of HCV infection during the so-called window period compared with anti
      HCV Ab assays and could be a useful alternative to HCV RNA detection or HCV core
      Ag assays for diagnosis or blood screening when nucleic acid technologies or HCV
      core Ag detection are not implemented.

PMID- 16081926
TI  - International and multicenter comparison of EUCAST and CLSI M27-A2 broth
      microdilution methods for testing susceptibilities of Candida spp. to
      fluconazole, itraconazole, posaconazole, and voriconazole.
AB  - The aim of this study was to compare MICs of fluconazole, itraconazole,
      posaconazole, and voriconazole obtained by the European Committee on Antibiotic
      Susceptibility Testing (EUCAST) and CLSI (formerly NCCLS) methods in each of six
      centers for 15 Candida albicans (5 fluconazole-resistant and 4 susceptible-dose
      dependent [S-DD] isolates), 10 C. dubliniensis, 7 C. glabrata (2 fluconazole
      resistant isolates), 5 C. guilliermondii (2 fluconazole-resistant isolates), 10
      C. krusei, 9 C. lusitaniae, 10 C. parapsilosis, and 5 C. tropicalis (1
      fluconazole-resistant isolate) isolates. CLSI MICs were obtained visually at 24
      and 48 h and spectrophotometric EUCAST MICs at 24 h. The agreement (within a 3
      dilution range) between the methods was species, drug, and incubation time
      dependent and due to lower EUCAST than CLSI MICs: overall, 94 to 95% with
      fluconazole and voriconazole and 90 to 91% with posaconazole and itraconazole
      when EUCAST MICs were compared against 24-h CLSI results. The agreement was lower
      (85 to 94%) against 48-h CLSI endpoints. The overall interlaboratory
      reproducibility by each method was > or =92%. When the comparison was based on
      CLSI breakpoint categorization, the agreement was 68 to 76% for three of the four
      species that included fluconazole-resistant and S-DD isolates; 9% very major
      discrepancies (< or =8 microg/ml versus > or =64 microg/ml) were observed among
      fluconazole-resistant isolates and 50% with voriconazole (< or =1 microg/ml
      versus > or =4 microg/ml). Similar results were observed with itraconazole for
      seven of the eight species evaluated (28 to 77% categorical agreement).
      Posaconazole EUCAST MICs were also substantially lower than CLSI MIC modes (0.008
      to 1 microg/ml versus 1 to > or =8 microg/ml) for some of these isolates.
      Therefore, the CLSI breakpoints should not be used to interpret EUCAST MIC data.

PMID- 16081927
TI  - Use of a heminested reverse transcriptase PCR assay for detection of astrovirus
      in environmental swabs from an outbreak of gastroenteritis in a pediatric primary
      immunodeficiency unit.
AB  - An outbreak of astrovirus gastroenteritis occurred in the Primary
      Immunodeficiency Unit at Newcastle General Hospital in March 2004. Environmental
      swabbing of the unit was undertaken after the outbreak, with multiple sites
      swabbed pre- and postcleaning. Astroviruses were detected in four environmental
      swabs and from two patient fecal samples using heminested reverse transcriptase
      PCR. An astrovirus genotype 3 strain was identified in both environmental swabs
      and fecal specimens and was the strain identified as being responsible for the
      outbreak. Environmental transmission of the virus was thought to have occurred by
      contamination of a syringe pump outside the laminar-flow curtain of a patient who
      was admitted with astrovirus gastroenteritis. This was subsequently transmitted
      to a cubicle next door and to a television/games console in a parents' room in
      the ward. Environmental monitoring of surfaces/equipment, using PCR assays for
      gastroenteric viruses in hospital situations where infection can give rise to
      serious clinical complications, may have a role in controlling and monitoring
      cleaning and the subsequent prevention of nosocomial transmission of
      gastroenteritis.

PMID- 16081928
TI  - Phylogenetic and pathotypic comparison of concurrent urine and rectal Escherichia
      coli isolates from men with febrile urinary tract infection.
AB  - Among men with febrile urinary tract infection (FUTI), whether the host's fecal
      flora is the source for the urine strain ("fecal-urethral" hypothesis), and
      whether pathogenesis is driven by prevalence versus special pathogenicity, are
      unknown. Accordingly, pretherapy urine isolates from 65 men with FUTI were
      compared with concurrent rectal isolates from the same hosts according to
      serotype, genomic profile, phylogenetic group, and virulence genotype. The host's
      multiple rectal colonies included only the urine clone in 25% of subjects, the
      urine clone plus additional clones in 22%, and only nonurine clones in 54%.
      Compared with the 67 unique rectal clones, the 65 urine isolates were
      significantly enriched for phylogenetic group B2, virulence-associated serotypes,
      and specific virulence genes and contained more virulence genes (median, 10
      versus 6: P < 0.001). In multivariable models, phylogenetic group B2, hlyD
      (hemolysin), cnf1 (cytotoxic necrotizing factor), iroN (siderophore receptor),
      ompT (outer membrane protease), and malX (pathogenicity island marker) most
      strongly predicted urine source. These findings challenge the fecal-urethral and
      prevalence hypotheses for FUTI pathogenesis and instead strongly support the
      possibility of alternate infection routes in some men and the special
      pathogenicity hypothesis. They also identify specific bacterial traits as
      potential targets for anti-FUTI interventions.

PMID- 16081929
TI  - Detection and quantification of human immunodeficiency virus type 1 p24 antigen
      in dried whole blood and plasma on filter paper stored under various conditions.
AB  - The quantification of human immunodeficiency virus type 1 (HIV-1) by an assay
      measuring heat-dissociated (HD) p24 antigen (Ag) in specimens of whole blood and
      plasma stored on filter paper, and of plasma stored in tubes, was compared to HIV
      1 RNA plasma levels determined by real-time reverse transcription (RT)-PCR. The
      stability of p24 Ag on filter paper under conditions simulating specimen
      transport was also evaluated. The HD p24 Ag in both plasma and whole-blood
      specimens stored on filter paper correlated with plasma HIV-1 RNA levels
      (Spearman rank rho = 0.74 [P < 0.0001] and rho = 0.56 [P = 0.0001],
      respectively). The sensitivity of the HD p24 Ag assay was similar when plasma and
      whole blood on filter paper were contrasted to the real-time RT-PCR assay (80%
      versus 82.5% and 78.6% versus 83.3%, respectively). However, while the
      specificity of the HD p24 Ag assay of plasma on filter paper was 100%, the
      specificity was diminished in whole-blood specimens. The storage of specimens on
      filter paper for 2 weeks at 37 degrees C, 24 degrees C, or 0 degrees C did not
      alter the detection or quantification of HD p24 Ag. These results suggest that
      transport and storage of plasma on filter paper and quantification of HD p24 Ag
      may be a reliable method for HIV-1 load monitoring.

PMID- 16081930
TI  - Distinct diversity of vacA, cagA, and cagE genes of Helicobacter pylori
      associated with peptic ulcer in Japan.
AB  - Colonization of the stomach mucosa by Helicobacter pylori is a major cause of
      acute and chronic gastric pathologies in humans. Several H. pylori virulence
      genes that may play a role in its pathogenicity have been identified. The most
      important determinants are vacA and cagA in the cag pathogenicity island (cagPAI)
      genes. In the present study, to consider the association of molecular genetics
      between vacA and the cagPAI regarding clinical outcome, we selected H. pylori
      strains with various genotypes of vacA in Japan and sequenced full-length vacA,
      cagA, and cagE genes. Sequencing of vacA and cagA genes revealed variable size,
      whereas the cagE gene was well conserved among strains. Each of the phylogenetic
      trees based on the deduced amino acid sequences of VacA, CagA, and CagE indicated
      that all three proteins were divided into two major groups, a Western group and
      an East Asian group, and the distributions of isolates exhibited similar patterns
      among the three proteins. The strains with s2 and s1a/m1a vacA genotypes and the
      Western-type 3' region cagA genotype were classified into the Western group, and
      the strains with the s1c/m1b vacA genotype and the East Asian-type 3' cagA
      genotype were included in the East Asian group. In addition, the prevalence of
      infection with the Western group strain was significantly higher in patients with
      peptic ulcer (90.0%, 9/10) than in patients with chronic gastritis (22.7%, 5/22)
      (chi2 = 12.64, P = 0.00057). These data suggest that the molecular genetics of
      vacA and cagPAI are associated and that the Western group with vacA and cagPAI
      genes is associated with peptic ulcer disease.

PMID- 16081931
TI  - Design of novel conformational and genotype-specific antigens for improving
      sensitivity of immunoassays for hepatitis C virus-specific antibodies.
AB  - The current commercially licensed enzyme-linked immunosorbent assays (ELISAs) for
      hepatitis C virus (HCV) mainly use recombinant proteins containing linear
      epitopes. There is evidence, however, that conformational epitopes of HCV are
      more immunoreactive. Thus, we have designed an HCV antibody assay that employs a
      conformational protein, NS3NS4a PI (with functional protease and helicase
      activities), and a linear fusion protein, multiple-epitope fusion antigen 7.1
      (MEFA 7.1) or MEFA 7.2. We have shown that NS3NS4a PI detects early
      seroconversion conformation-sensitive antibodies better than c33c antigen. The
      correct conformation of NS3NS4a PI also cross-reacts with different genotype
      samples better than the c33c antigen. MEFA 7.1 and MEFA 7.2 incorporate all the
      major immunodominant and genotype-specific epitopes of HCV core, E1, E2
      hypervariable region 1 (HVR1), E2 HVR1-plus-HVR2 consensus, NS3, NS4, and NS5.
      Since MEFA 7.1 is degraded by the active NS3NS4a PI protease, we designed a
      second MEFA 7.2 construct in which the six protease cleavage sites found in MEFA
      7.1 were eliminated by amino acid mutation. We demonstrate here that MEFA 7.2
      remains intact in the presence of NS3NS4a PI and preserves the epitopes present
      in MEFA 7.1. Compared to currently licensed assays, an ELISA incorporating a
      combination of the two antigens NS3NS4a PI and MEFA 7.1 or 7.2 demonstrates
      better serotype sensitivity and detects seroconversion earlier in many
      commercially available panels. We believe that an assay using NS3NS4a PI and MEFA
      7.1 or 7.2 may have the potential to replace current HCV immunoassays for better
      sensitivity.

PMID- 16081932
TI  - Bifidobacterial lipoglycan as a new cause for false-positive platelia Aspergillus
      enzyme-linked immunosorbent assay reactivity.
AB  - We previously hypothesized that a lipoglycan of Bifidobacterium bifidum subsp.
      pennsylvanicum cross-reacts with the Platelia Aspergillus (PA) enzyme-linked
      immunosorbent assay (ELISA) based on the presence of galactofuranosyl epitopes in
      the cell wall (M. A. S. H. Mennink-Kersten, R. R. Klont, A. Warris, H. J. M. Op
      den Camp, and P. E. Verweij, Lancet 363:325-327, 2004). We tested this hypothesis
      by testing bacterial suspensions of different bifidobacterial species and other
      gram-positive and -negative bacteria with the PA ELISA, which is used to detect
      circulating galactomannan for the serodiagnosis of invasive aspergillosis.
      Furthermore, neonatal fecal samples were enumerated for bifidobacteria by
      fluorescence in situ hybridization (FISH) and tested for PA ELISA reactivity. All
      bifidobacteria, except B. infantis and B. adolescentis, showed reactivity 6- to
      600-fold higher compared to the controls (i.e., Micrococcus luteus and
      Propionibacterium freudenreichii, which contain a cell wall lipomannan).
      Eggerthella lenta showed a 25-fold-higher reactivity. ELISA reactivity was
      clearly shown to be associated with bacterial lipoglycans containing a beta-1,5
      galactofuranosyl chain. All neonatal feces showed PA ELISA reactivity and
      associated numbers of bifidobacteria. Since high concentrations of bifidobacteria
      are present in the human gut, these bacteria or excreted lipoglycan may cause
      false serum PA ELISA reactivity in selected patient groups, especially neonates.

PMID- 16081933
TI  - Association of tumor necrosis factor a-2 and a-8 microsatellite alleles with
      human papillomavirus and squamous intraepithelial lesions among women in Brazil.
AB  - Infection with oncogenic human papillomavirus (HPV) is considered to be the major
      risk factor for cervical cancer. Tumor necrosis factor (TNF) is a pluripotent
      cytokine that plays an important role in inhibiting the action of microbial
      agents, and TNF microsatellite polymorphisms have been associated with several
      diseases, including cancer and viral infections. This study analyzed the
      associations between TNFa to -e microsatellite polymorphisms and the severity of
      squamous intraepithelial lesions (SIL), according to the presence of the
      oncogenic HPV16 and HPV18 types. Samples from 146 HPV-positive women with low
      grade SIL (LSIL) and high-grade SIL (HSIL) and samples from 101 healthy women
      were studied. TNF microsatellite polymorphism typing and HPV detection and typing
      were performed using PCR-amplified DNA hybridized with sequence-specific primers.
      Data were analyzed by Fisher's exact test using the GENEPOP software. Significant
      associations were observed between LSIL and the TNFa-8 allele (4/166; P = 0.04),
      as well as between TNFa-2 with HPV18 only (16/44; P = 0.002) and TNFa-2 with
      HPV18 coinfection with HPV16 (16/44; P = 0.001). Patients exhibiting the TNFa-2
      allele and harboring HPV18, in the presence or absence of coinfection with HPV16,
      had an increased risk of HSIL occurrence (13/38; P = 0.04; 5/10; P = 0.04)
      compared to patients with other HPV types. These results suggest that the TNFa-8
      allele is associated with increased susceptibility to the occurrence of LSIL and
      that despite the presence of a high TNF-alpha production allele, the ability of
      HPV18 to resist the inhibitory effects of TNF-alpha may contribute to the
      occurrence of infection and consequently to HSIL in women with cervical HPV18
      infection.

PMID- 16081934
TI  - Clinical and microbiological features of Inquilinus sp. isolates from five
      patients with cystic fibrosis.
AB  - Patients with cystic fibrosis (CF) may be colonized with unusual gram-negative
      bacilli whose identification is difficult and clinical impact unclear. We
      describe the clinical and microbiological features of five colonizations with
      organisms belonging to the recently described genus Inquilinus in CF patients.
      Isolates were identified from Burkholderia cepacia selective medium by means of
      16S rRNA analysis. All of them were resistant to colistin, penicillins,
      cephalosporins, and monobactams but exhibited a remarkable susceptibility to
      imipenem. One of the five patients was transiently colonized with a nonmucoid
      isolate, whereas the four other patients were persistently colonized over the
      period of follow-up (8 to 21 months) with mucoid isolates. Pulsed-field gel
      electrophoresis of SpeI-digested genomic DNA was powerful for strain genotyping
      and demonstrated the clonality of Inquilinus sp. colonization for the two
      patients tested. Clinical evolution after the onset of Inquilinus was
      heterogeneous, but for at least one patient the lung function worsened and
      eradication of Inquilinus sp. was unsuccessful despite several imipenem courses.
      Finally, Inquilinus spp. may represent a new threat for CF patients due to their
      mucoid characteristic, their multiresistant pattern to antibiotics, and their
      ability to persist in the respiratory tract.

PMID- 16081935
TI  - Identification of candidate periodontal pathogens and beneficial species by
      quantitative 16S clonal analysis.
AB  - Most studies of the bacterial etiology of periodontitis have used either culture
      based or targeted DNA approaches, and so it is likely that pathogens remain
      undiscovered. The purpose of this study was to use culture-independent,
      quantitative analysis of biofilms associated with chronic periodontitis and
      periodontal health to identify pathogens and beneficial species. Samples from
      subjects with periodontitis and controls were analyzed using ribosomal 16S
      cloning and sequencing. Several genera, many of them uncultivated, were
      associated with periodontitis, the most numerous of which were gram positive,
      including Peptostreptococcus and Filifactor. The genera Megasphaera and
      Desulfobulbus were elevated in periodontitis, and the levels of several species
      or phylotypes of Campylobacter, Selenomonas, Deferribacteres, Dialister,
      Catonella, Tannerella, Streptococcus, Atopobium, Eubacterium, and Treponema were
      elevated in disease. Streptococcus and Veillonella spp. were found in high
      numbers in all samples and accounted for a significantly greater fraction of the
      microbial community in healthy subjects than in those with periodontitis. The
      microbial profile of periodontal health also included the less-abundant genera
      Campylobacter, Abiotrophia, Gemella, Capnocytophaga, and Neisseria. These newly
      identified candidates outnumbered Porphyromonas gingivalis and other species
      previously implicated as periodontopathogens, and it is not clear if newly
      identified and more numerous species may play a more important role in
      pathogenesis. Finally, more differences were found in the bacterial profile
      between subjects with periodontitis and healthy subjects than between deep and
      shallow sites within the same subject. This suggests that chronic periodontitis
      is the result of a global perturbation of the oral bacterial ecology rather than
      a disease-site specific microbial shift.

PMID- 16081936
TI  - Early immune response to the components of the type III system of Pseudomonas
      aeruginosa in children with cystic fibrosis.
AB  - The lungs of patients with cystic fibrosis (CF) are colonized initially by
      Pseudomonas aeruginosa, which is associated with progressive lung destruction and
      increased mortality. The pathogenicity of P. aeruginosa is caused by a number of
      virulence factors, including exotoxin A (ETA) and the type III cytotoxins (ExoS,
      ExoT, ExoU, and ExoY). P. aeruginosa contacts the plasma membrane to deliver type
      III cytotoxins through a channel formed by PopB, PopD, and PcrV; ETA enters
      mammalian cells via receptor-mediated endocytosis. The Wisconsin CF Neonatal
      Screening Project is a longitudinal investigation to assess the potential
      benefits and risks of newborn screening for CF; the project was the source of
      serum samples used in this study. Past studies evaluated the longitudinal
      appearance of antibodies to ETA and elastase and P. aeruginosa infections in
      patients with CF. The current study characterized the longitudinal appearance of
      antibodies to components of the type III system in children with CF. Western blot
      analyses showed that serum antibodies to PopB, PcrV, and ExoS were common.
      Longitudinal enzyme-linked immunosorbent assays determined that the first
      detection of antibodies to pooled ExoS/PopB occurred at a time similar to those
      of detection of antibodies to a P. aeruginosa cell lysate and the identification
      of oropharyngeal cultures positive for P. aeruginosa. This indicates that
      children with CF are colonized early with P. aeruginosa expressing the type III
      system, implicating it in early pathogenesis, and implies that surveillance of
      clinical symptoms, oropharyngeal cultures, and seroconversion to type III
      antigens may facilitate early detection of P. aeruginosa infections.

PMID- 16081937
TI  - Model for assessment of proficiency of human immunodeficiency virus type 1
      sequencing-based genotypic antiretroviral assays.
AB  - Use of sequencing-based genotyping as a diagnostic assay for human
      immunodeficiency virus (HIV) antiretroviral resistance is increasing. Periodic
      evaluation of the proficiency of laboratories performing this assay should be
      established. It is important to identify components of the assay that influence
      the generation of reliable sequencing data and that should and can be monitored.
      A model was developed to determine what parameters were reasonable and feasible
      for assessing the performance of genotyping assays. Ten laboratories using the
      genotyping platform, HIV-1 Genotyping System (HGS) v. 1 and software versions 1.1
      or 2.0, participated in two rounds of testing. For each round, each group was
      sent a panel consisting of three clinical samples to sequence in real time. Six
      months later, seven laboratories using the TRUGENE HIV-1 Genotyping Kit
      participated in a separate round, working with both panels at the same time.
      Analysis of the data showed that one main indicator of genotyping proficiency was
      achievement of > or =98% sequence homology of a sample tested to a group
      consensus sequence for that sample. A second was concordant identification of
      codons at sites identified with resistance mutations in the sample, although
      scoring of these criteria is still undetermined from this study. These criteria
      are applicable to all sequence-based genotyping platforms and have been used as a
      baseline for assessing the performance of genotyping for the determination of
      antiretroviral resistance in our ongoing proficiency program.

PMID- 16081938
TI  - Statistical analyses of complex denaturing gradient gel electrophoresis profiles.
AB  - Studies using molecular techniques have demonstrated that a culture-based
      approach can severely underestimate the bacterial diversity in most environments.
      One of the molecular techniques that has been applied in microbial ecology is
      denaturing gradient gel electrophoresis (DGGE). The purpose of this study was to
      investigate differences in the microbiota of plaque, using a number of analysis
      techniques, from children without gingivitis (n = 30) and from those with
      gingivitis (n = 30). Extracted DNA from gingival margin plaque was subjected to
      PCR targeting the 16S rRNA gene using universal primers. DGGE profiles were
      analyzed in three ways. (i) Bacterial diversity was compared between cohorts by
      using the Shannon-Wiener index (also known as the Shannon-Weaver index). (ii) A
      hierarchical cluster analysis of the banding patterns was calculated and
      expressed as a dendrogram. (iii) Individual DGGE bands and their intensities for
      both cohorts were compared using a logistic regression analysis. The Shannon
      Wiener indices demonstrated a greater bacterial diversity associated with no
      gingivitis plaque (P = 0.009). Dendrograms demonstrated that seven clades
      associated with gingivitis and five clades associated with no gingivitis. The
      logistic regression demonstrated that one band was significantly associated with
      no gingivitis (P = 0.001), while two bands were significantly associated with
      gingivitis (P = 0.005 and P = 0.042). In conclusion, this study demonstrates that
      the development of gingivitis might be accompanied by a decrease in bacterial
      diversity. Furthermore, we have demonstrated that logistic regression is a good
      statistical method for analyzing and characterizing DGGE profiles.

PMID- 16081939
TI  - Comparison of Staphylococcus aureus genotypes recovered from cases of bovine,
      ovine, and caprine mastitis.
AB  - Staphylococcus aureus is an important pathogen in domestic ruminants. The main
      objective of this study was to determine the similarity of epidemiologically
      unrelated S. aureus isolates from bovine, ovine, and caprine mastitis. By pulsed
      field gel electrophoresis, 160 different pulsotypes (PTs) were identified among
      905 isolates recovered from 588 herds in 12 counties in Norway. Based on
      estimates of similarity, using an 80% cluster cutoff, the isolates were assigned
      to 47 clusters. One cluster included 62% of all the isolates and more than 45% of
      the isolates from each host species. Twenty-three PTs included isolates from more
      than one host species; these 23 PTs represented 72% of all the isolates. The six
      most prevalent PTs included isolates from all host species and contained 45% of
      the bovine isolates, 54% of the ovine isolates, and 37% of the caprine isolates.
      Antimicrobial susceptibility testing of 373 of the isolates revealed resistance
      to penicillin in 2.9% and to streptomycin in 2.4%; only 1.9% were resistant to 1
      of the other 11 antimicrobials tested. The results of this study suggest that a
      small number of closely related genotypes are responsible for a great proportion
      of S. aureus mastitis cases in cows, ewes, and goats in Norway and that these
      genotypes exhibit little or no host preference among these species. Selection due
      to antimicrobial resistance appears not to have contributed to the predominance
      of these genotypes.

PMID- 16081940
TI  - Comparative sequencing of the serine-aspartate repeat-encoding region of the
      clumping factor B gene (clfB) for resolution within clonal groups of
      Staphylococcus aureus.
AB  - Molecular techniques such as spa typing and multilocus sequence typing use DNA
      sequence data for differentiating Staphylococcus aureus isolates. Although spa
      typing is capable of detecting both genetic micro- and macrovariation, it has
      less discriminatory power than the more labor-intensive pulsed-field gel
      electrophoresis (PFGE) and costly genomic DNA microarray analyses. This
      limitation hinders strain interrogation for newly emerging clones and outbreak
      investigations in hospital or community settings where robust clones are endemic.
      To overcome this constraint, we developed a typing system using DNA sequence
      analysis of the serine-aspartate (SD) repeat-encoding region within the gene
      encoding the keratin- and fibrinogen-binding clumping factor B (clfB typing) and
      tested whether it is capable of discriminating within clonal groups. We analyzed
      116 S. aureus strains, and the repeat region was present in all isolates, varying
      in sequence and in length from 420 to 804 bp. In a sample of 36 well
      characterized genetically diverse isolates, clfB typing subdivided identical spa
      and PFGE clusters which had been discriminated by whole-genome DNA microarray
      mapping. The combination of spa typing and clfB typing resulted in a
      discriminatory power (99.5%) substantially higher than that of spa typing alone
      and closely approached that of the whole-genome microarray (100.0%). clfB typing
      also successfully resolved genetic differences among isolates differentiated by
      PFGE that had been collected over short periods of time from single hospitals and
      that belonged to the most prevalent S. aureus clone in the United States. clfB
      typing demonstrated in vivo, in vitro, and interpatient transmission stability
      yet revealed that this locus may be recombinogenic in a primarily clonal
      population structure. Taken together, these data show that the SD repeat-encoding
      region of clfB is a highly stable marker of microvariation, that in conjunction
      with spa typing it may serve as a DNA sequence-based alternative to PFGE for
      investigating genetically similar strains, and that it is useful for analyzing
      collections of isolates in both long-term population-based and local
      epidemiologic studies.

PMID- 16081941
TI  - In vitro cultivation of a zoonotic Babesia sp. isolated from eastern cottontail
      rabbits (Sylvilagus floridanus) on Nantucket Island, Massachusetts.
AB  - A Babesia sp. found in eastern cottontail rabbits (Sylvilagus floridanus) on
      Nantucket Island, Massachusetts, is the same organism that caused human
      babesiosis in Missouri and Kentucky, on the basis of morphology and identical
      small-subunit rRNA (SSU rRNA) gene sequences. Continuous cultures of the rabbit
      parasite were established from infected blood samples collected from two
      cottontail rabbits livetrapped on Nantucket Island. HL-1 medium or minimal
      essential medium alpha medium supplemented with 20% human serum best supported in
      vitro propagation of the parasite in human or cottontail erythrocytes,
      respectively. Parasite growth was not sustained in domestic-rabbit erythrocytes
      or in medium supplemented with domestic-rabbit serum. The cultured parasites were
      morphologically indistinguishable from the Kentucky human isolate. Transmission
      electron microscopy revealed similar fine structures of the parasite regardless
      of the host erythrocyte utilized in the cultures. Two continuous lines of the
      zoonotic Babesia sp. were established and confirmed to share identical SSU rRNA
      gene sequences with each other and with the Missouri and Kentucky human Babesia
      isolates.

PMID- 16081942
TI  - Regulated expression of the beta2-toxin gene (cpb2) in Clostridium perfringens
      type a isolates from horses with gastrointestinal diseases.
AB  - Recent epidemiological studies suggested that cpb2-positive Clostridium
      perfringens isolates are associated with gastrointestinal (GI) diseases in
      horses. These putative relationships, indicated by PCR genotyping, were tested in
      the present study by further genotyping and phenotyping of 23 cpb2-positive C.
      perfringens isolates from horses with GI disease (referred to hereafter as horse
      GI disease isolates). Our beta2-toxin (CPB2) Western blot analyses demonstrated
      that all of the tested isolates were unable to produce detectable levels of CPB2.
      However, Southern blot and nucleotide sequencing analyses identified intact cpb2
      open reading frames in all of our surveyed horse GI disease isolates.
      Furthermore, reverse transcriptase PCR and Northern blot analyses showed that
      cpb2 genes in all of our surveyed horse GI disease isolates were
      transcriptionally active, i.e., an approximately 1.2-kb cpb2-specific mRNA was
      identified in total RNA from our surveyed isolates. The levels of cpb2 mRNA in
      CWC245 (a high-CPB2-producing pig strain) and our surveyed horse GI disease
      isolates differed to such an extent (35-fold) that this difference could be
      considered as a major cause of the difference in levels of CPB2 production by
      CWC245 and horse GI disease isolates. This finding received further support from
      our observation that the complementing strain 106902(pMRS140), which produced
      significantly higher levels of mRNA than strain 106902, produced high levels of
      CPB2. Collectively, our results indicated that there is a positive correlation
      between cpb2 transcription levels and the amount of CPB2 produced by a C.
      perfringens cell and that decreased transcription and/or message instability may
      be involved, at least in part, in the low CPB2 production noted for horse GI
      disease isolates in comparison to that noted for pig GI disease isolate CWC245.

PMID- 16081943
TI  - Molecular evolutionary history of tubercle bacilli assessed by study of the
      polymorphic nucleotide within the nitrate reductase (narGHJI) operon promoter.
AB  - A well-characterized collection of Mycobacterium tuberculosis complex (MTC)
      isolates, representing all known subspecies as well as some relevant genotypic
      families of M. tuberculosis, was analyzed for the newly discovered narGHJI -215 C
      to-T promoter single-nucleotide polymorphism (SNP). This point mutation has been
      shown in earlier studies to be responsible for the differential nitrate reductase
      activity of M. tuberculosis versus M. bovis. As previously defined by the
      presence or the absence of the TbD1 genetic locus, the group included both the
      "modern" W-Beijing, Haarlem, and Central-Asian1 (CAS1) families as well as the
      "ancestral" East-African-Indian (EAI) clade. Interestingly, among "modern" M.
      tuberculosis isolates, those previously classified as Principal Genetic Group 1
      (PGG1) organisms by katG463-gyrA95 polymorphism analysis did not present the two
      banded narGHJI restriction fragment length polymorphism analysis of PCR products
      pattern common to the other PGG1 MTC members, including the "ancestral" M.
      tuberculosis isolates. Instead, they showed a one-banded pattern, aligning them
      with other evolutionarily recent M. tuberculosis isolates of the PGG2 and PGG3
      groups, such as Haarlem, Latin-American and Mediterranean (LAM), and X families.
      The presence of a nitrate reductase producer phenotype in "Mycobacterium
      canettii" and some "ancestral" M. tuberculosis isolates, despite a two-band -215C
      genotype, argues in favor of an alternate mechanism to explain the differential
      nitrate reductase activity of certain PGG1 subspecies of the MTC. Overall, these
      findings may help to establish the precise evolutionary history of important
      genotype families such as W-Beijing and suggest that the -215T genotype may have
      contributed the virulence, spread, and evolutionary success of "modern" M.
      tuberculosis strains compared to the remaining MTC organisms.

PMID- 16081944
TI  - Simultaneous visual detection of multiple viral amplicons by dipstick assay.
AB  - A sensitive, simple, and instrument-independent method for the visual detection
      and identification of multiple nucleic acid amplicons by dipstick has been
      developed. This method is based on nucleic acid hybridization on the dipstick
      membrane and a signal amplification system to allow visual detection. With
      hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency
      virus type 1 (HIV-1) as model analytes, it is demonstrated that the visual
      dipstick test combined with multiplex reverse transcription (RT)-PCR for the
      amplification of viral nucleic acid provides a specific and sensitive detection
      method. The RT-PCR products were detected by the dipstick with an efficiency
      similar to that of a complex, expensive, and instrument-dependent method based on
      fluorogenic oligonucleotide probes. The detection limits of the dipstick combined
      with multiplex RT-PCR were 50, 125, and 500 IU/ml for HBV DNA, HCV RNA, and HIV-1
      RNA, respectively. The dipstick assay detected with similar efficiencies
      amplicons derived from strains of HBV genotypes A through F, HCV genotypes 1 to
      6, and HIV-1 subtypes A through H as well as CRF02 circulating recombinant forms
      of HIV-1. Analysis of 295 clinical samples and 19 pools of 10 plasma specimens
      from blood donors revealed that multiplex dipstick detection was reproducible,
      sensitive, and specific. The visual dipstick detection of multiple amplicons thus
      provides an attractive alternative to complex, instrument-dependent detection
      methods currently in use for nucleic acid testing. This new and sensitive method
      for nucleic acid detection should increase the availability of genomic screening
      in resource-limited settings and its applicability to near-patient testing.

PMID- 16081945
TI  - Value of serological testing for diagnosis of legionellosis in outbreak patients.
AB  - Serum antibody detection tests and a urine antigen detection technique were
      compared in samples from 116 patients epidemiologically characterized as
      belonging to a legionellosis outbreak. Sera were tested by enzyme-linked
      immunosorbent assays (ELISAs) for immunoglobulin M (IgM) and IgG plus IgM and by
      immunofluorescent assays (IFAs) for IgG, IgM, IgA, and polyimmunoglobulin using
      commercial kits (Vircell); concentrated urines were tested with the Binax NOW
      Legionella test. ELISA for IgM, ELISA for IgG plus IgM, antigenuria detection,
      and IFA for IgM were able to diagnose 72.3%, 60.5%, 53.3%, and 51.4%,
      respectively, of patients. Antigenuria was present in 53.8% of first samples,
      ELISA detected IgM in 29.7%, ELISA detected IgG plus IgM in 7.9%, and IFA
      detected IgM in 3.9%. Ten antigenuria-negative first samples tested serologically
      positive, 9 of them to IgM by ELISA. Despite the single source of the samples
      included in the study, detection of IgM using a sensitive technique such as ELISA
      seems to be a suitable complement to antigenuria detection for the diagnosis of
      legionellosis.

PMID- 16081946
TI  - Novel 5-flucytosine-resistant clade of Candida dubliniensis from Saudi Arabia and
      Egypt identified by Cd25 fingerprinting.
AB  - DNA fingerprinting of Candida dubliniensis isolates using the species-specific
      probe Cd25 previously showed that this species consists of two distinct groups,
      termed Cd25 group I and Cd25 group II. The present study investigated the
      population structure of 30 C. dubliniensis oral isolates from Saudi Arabia and
      Egypt using Cd25 fingerprinting and rRNA gene internal transcribed spacer region
      based genotyping. Cd25 fingerprinting analysis of these isolates revealed two
      distinct populations, the first of which consisted of 10 closely related genotype
      1 isolates (average similarity coefficient [S(AB)] value, 0.86). The second
      population of 20 isolates was much more heterogeneous (average S(AB) value, 0.35)
      and consisted of two distinct subpopulations, one of which consisted of genotype
      3 isolates (n = 13) and the other of genotype 4 isolates (n = 7). A mixed
      dendrogram generated from the fingerprint data from the 30 Saudi Arabian and
      Egyptian isolates, 5 Israeli isolates, and 51 previously characterized
      international isolates (32 of Cd25 group I and 19 of Cd25 group II) revealed the
      presence of three distinct main clades. The first corresponded to the previously
      described Cd25 group I and contained all the Saudi Arabian, Egyptian, and Israeli
      genotype 1 isolates mixed with international isolates. The second clade
      corresponded to the previously described Cd25 group II and contained three
      Israeli isolates, one genotype 2 isolate, one genotype 3 isolate, and a genotype
      4 variant isolate, which were mixed with international isolates. The third clade
      has not been described before and consisted solely of the 20 Saudi Arabian and
      Egyptian genotype 3 and 4 isolates identified in this study and a previously
      described genotype 4 Israeli isolate. All 20 Cd25 group III isolates exhibited
      high-level resistance to 5-flucytosine (MIC > or = 128 microg/ml), whereas all
      Cd25 group I and Cd25 group II isolates tested (10 Saudi Arabian and Egyptian, 16
      Israeli, and 24 international) were susceptible to 5-flucytosine (MIC < or =
      0.125 microg/ml). The results of this study show for the first time the presence
      of a novel 5-flucytosine-resistant clade of C. dubliniensis (Cd25 group III) that
      is predominant among isolates from Saudi Arabia and Egypt and absent from a
      previously characterized international collection of 98 isolates from 15
      countries.

PMID- 16081947
TI  - Detection of Streptococcus pneumoniae antigen in bronchoalveolar lavage fluid
      samples by a rapid immunochromatographic membrane assay.
AB  - We conducted a retrospective study to evaluate an immunochromatographic membrane
      test (ICT), applied to bronchoalveolar lavage (BAL) fluid samples obtained in
      patients with suspected pneumonia, for the detection of Streptococcus pneumoniae
      antigen. The NOW Streptococcus pneumoniae test was assessed on 96 BAL fluid
      samples. Sensitivity was tested in 20 samples obtained from patients diagnosed as
      having pneumococcal pneumonia (growth of S. pneumoniae in blood cultures and/or
      in BAL fluid samples of > or =10(4) CFU/ml). Specificity was tested in BAL fluid
      samples of nonpneumococcal etiology (n = 41) and in samples with no respiratory
      pathogen and a total bacterial count of <10(4) CFU/ml (n = 35). Using the ICT,
      pneumococcal antigen was detected in 29 (30.2%) BAL fluid samples, with a
      sensitivity of 95.0% (95% confidence interval [CI], 90.6% to 99.4%) and a
      specificity of 86.8% (95% CI, 80.1% to 93.8%). The ICT was easy to perform and
      revealed unequivocal and reproducible results. No interference was observed with
      high cell counts, red blood cells, or elevated protein levels. Four out of 10
      false-positive readings occurred in samples with S. pneumoniae counts below the
      10(4) CFU/ml threshold limit of pneumonia. In BAL fluid samples obtained after
      pneumococcal bacteremia, positive test results were found for up to 35 days after
      bacteremia. The ICT test applied to BAL fluid specimens is reproducible and
      accurate in the diagnosis of pneumococcal antigen. Further studies are required
      to establish the impact of the ICT on patient care.

PMID- 16081948
TI  - Biochemical differentiation and comparison of Desulfovibrio species and other
      phenotypically similar genera.
AB  - Seventeen human clinical isolates representing four species of Desulfovibrio were
      characterized using 16S rRNA gene sequences and tests for catalase, indole,
      nitrate, bile, urease, formate-fumarate stimulation, desulfoviridin, motility,
      and hydrogen sulfide production, plus susceptibility to antimicrobial agents.
      Eighty additional strains representing 10 phenotypically similar genera
      (Bilophila, Selenomonas, Capnocytophaga, Campylobacter, Bacteroides, Sutterella,
      Anaerobiospirillum, Dialister, Veillonella, and Mobiluncus) were included for
      comparison. All Desulfovibrio species produced H2S and were desulfoviridin
      positive, and all Desulfovibrio species except D. piger were motile. The four
      Desulfovibrio species could be distinguished from each other using tests for
      catalase, indole, nitrate, urease, and growth on bile, with the following results
      (positive [+], negative [-], growth [G], and no growth [NG]): for D. piger, -, -,
      -, -, and G, respectively; for D. fairfieldensis, +, -, +, -, and G,
      respectively; for D. desulfuricans, -, -, +, +, and NG, respectively; and for D.
      vulgaris, -, +, -, -, and G, respectively. Resistance to the 10-microg colistin
      disk separated the Desulfovibrio species from most of the other genera, which
      were usually susceptible. These simple tests were useful for characterizing the
      Desulfovibrio species and differentiating them from other phenotypically similar
      genera.

PMID- 16081949
TI  - Use of the Roche LightCycler Strep B assay for detection of group B Streptococcus
      from vaginal and rectal swabs.
AB  - The results for a real-time PCR assay, using the LightCycler Strep B analyte
      specific reagents (Roche Diagnostics Corporation, Indianapolis, Ind.), were
      compared to a direct plate method combined with a broth enrichment culture method
      for detection of group B streptococcus colonization in pregnant women. Two
      separate evaluations were conducted using two different automated nucleic
      extraction instruments, the MagNA Pure LC instrument (Roche Diagnostics
      Corporation) and the lower-capacity MagNA Pure Compact instrument (Roche
      Diagnostics Corporation). The sensitivities, specificities, and positive and
      negative predictive values for the different evaluation methods were as follow:
      for the LightCycler Strep B assay with MagNA Pure LC, 100, 97, 90, and 100%,
      respectively; for the LightCycler Strep B assay with MagNA Pure Compact, 92.5,
      99, 97, and 97.5%, respectively. The LightCycler Strep B assay combined with
      either MagNA Pure LC or MagNA Pure Compact extraction is a suitable method for
      detecting group B streptococcus colonization in pregnant women. An advantage of
      the LightCycler assay over culture is the considerably reduced turnaround time
      for results.

PMID- 16081950
TI  - Detection of toxB, a plasmid virulence gene of Escherichia coli O157, in
      enterohemorrhagic and enteropathogenic E. coli.
AB  - The virulence plasmid of Escherichia coli O157 strain EDL933 carries a 10-kb
      putative virulence gene designated toxB. Little is known about the distribution
      of this gene among E. coli O157 strains or its presence in other
      enterohemorrhagic E. coli (EHEC) and enteropathogenic E. coli (EPEC) strains. We
      developed PCR and hybridization tools for the detection of the entire toxB
      sequence and investigated its presence in a collection of EHEC O157 strains and
      other EHEC and EPEC strains belonging to different serogroups and isolated from
      different sources. The EHEC O157 strains reacted with all of the PCR primers and
      probes used, thus indicating the presence of a complete toxB gene regardless of
      the human or bovine origin of the isolates. Similar positive reactions were
      observed for about 50% of the EHEC O26 strains tested and a few other EHEC and
      EPEC strains. However, the size of the DNA fragments hybridizing with the toxB
      probes differed from that of the positive fragments from EHEC O157, suggesting a
      polymorphism in the toxB genes present in the different E. coli serogroups.
      Moreover, several EHEC and EPEC strains belonging to different serogroups reacted
      with only some of the genetic tools used, suggesting either the existence of
      major variants of toxB or the presence of fragments of the gene. Southern
      blotting analysis showed that toxB sequences were located on large plasmids in
      EHEC and EPEC O26 as well.

PMID- 16081951
TI  - Evaluation of the ReSSQ assay in relation to the COBAS AMPLICOR CMV MONITOR test
      and an in-house nested PCR method for detection of cytomegalovirus DNA.
AB  - The ReSSQ CMV assay is a novel commercially available kit for quantification of
      cytomegalovirus (CMV), based on real-time PCR with a peptide nucleic acid probe
      coupled with a single dye. In combination with the LightCycler, the ReSSQ CMV
      assay was evaluated with respect to specificity, PCR inhibition, linearity,
      reproducibility, and sensitivity. All nontested CMV materials were negative, and
      the assay was not inhibited by the use of different anticoagulants or other
      factors that may influence blood samples. The dynamic range was between 10 and 5
      x 10(8) copies/PCR, and intra- and interassay variabilities were below 0.10 and
      0.12 log10 standard deviations, respectively. Assay sensitivity was validated by
      analysis of 24 samples from a proficiency panel and by comparison to a nested in
      house CMV PCR and the COBAS AMPLICOR CMV MONITOR test, using 159 clinical
      samples. Results from the proficiency panel were well in accordance with input
      values over the entire range of viral concentrations tested (50 to 31,250
      copies/ml). The association between the ReSSQ CMV assay and the in-house PCR was
      in agreement in 90% of the clinical samples, and discordant results were found
      for all types of sample materials analyzed. The ReSSQ CMV and COBAS AMPLICOR
      assays showed no significant differences for samples containing >1,000 CMV
      copies/ml, but results differed to a greater extent at lower viral
      concentrations. The results demonstrate that the ReSSQ CMV assay is a CMV
      specific, robust, and reproducible method and hence is well suited for routine
      use in clinical virology laboratories.

PMID- 16081952
TI  - Predominance of rotavirus genotype G9 during the 1999, 2000, and 2002 seasons
      among hospitalized children in the city of Salvador, Bahia, Brazil: implications
      for future vaccine strategies.
AB  - Two hundred eight of 648 (32%) diarrheal stool samples collected from
      hospitalized children under 5 years of age during a 3-year period (1999, 2000,
      and 2002) in the city of Salvador, in the state of Bahia, Brazil, were rotavirus
      positive. One hundred sixty-four of 208 (78.8%) rotavirus-positive samples had
      genotype G9 specificity, predominantly in association with P[8]. Other
      specificities detected were G1 (12.0%) and G4 (1.4%). Viruses with G2, G3, or
      P[4] specificity were not detected. Rotavirus genotype G9 predominated during
      each of the three seasons studied; it represented 89.2% of rotavirus strains
      detected in 1999, 85.3% in 2000, and 74.5% in 2002. G1 viruses (the globally most
      common G type) have a unique epidemiological characteristic of maintaining
      predominance during multiple consecutive rotavirus seasons. We have shown in this
      study for the first time that the G9 viruses also have a similar epidemiological
      characteristic, albeit for a shorter period of surveillance. The next generation
      of rotavirus vaccines will need to provide adequate protection against disease
      caused by G9 viruses.

PMID- 16081953
TI  - Superiority of molecular techniques for identification of gram-negative, oxidase
      positive rods, including morphologically nontypical Pseudomonas aeruginosa, from
      patients with cystic fibrosis.
AB  - Phenotypic identification of gram-negative bacteria from Cystic Fibrosis (CF)
      patients carries a high risk of misidentification. Therefore, we compared the
      results of biochemical identification by API 20NE with 16S rRNA gene sequencing
      in 88 gram-negative, oxidase-positive rods, other than morphologically and
      biochemically typical P. aeruginosa, from respiratory secretions of CF patients.
      The API 20NE allowed correct identification of the bacterial species in 15 out of
      88 (17%) isolates investigated. Agreement between the API and the 16S rRNA gene
      sequencing results was high only in isolates with an API result classified as
      "excellent identification". Even API results classified as "very good
      identification" or "good identification" showed a high rate of misidentification
      (67% and 84%). Fifty-two isolates of morphological and biochemical nontypical
      Pseudomonas aeruginosa, representing 59% of all isolates investigated, were not
      identifiable or misidentified in the API 20NE. Therefore, rapid molecular
      diagnostic techniques like real-time PCR and fluorescence in situ hybridization
      (FISH) were evaluated in this particular group of bacteria for identification of
      the clinically most relevant pathogen, P. aeruginosa. The LightCycler PCR assay
      with a P. aeruginosa-specific probe showed a sensitivity and specificity of 98.1%
      and 100%, respectively. For FISH analysis, a newly designed P. aeruginosa
      specific probe had a sensitivity and specificity of 100%. In conclusion,
      molecular methods are superior over biochemical tests for identification of gram
      negative, oxidase-positive rods in CF patients. In addition, real-time PCR and
      FISH allowed identification of morphologically nontypical isolates of P.
      aeruginosa within a few hours.

PMID- 16081954
TI  - Distribution of the serine protease autotransporters of the Enterobacteriaceae
      among extraintestinal clinical isolates of Escherichia coli.
AB  - Urinary tract infections continue to be among the most common extraintestinal
      diseases. Cystitis in women is by far the most common urinary tract infection;
      pyelonephritis in both sexes and prostatitis in men are more severe but less
      frequent complaints. Escherichia coli is by far the most common cause of urinary
      tract infection. It is believed that uropathogenic E. coli is adept at colonizing
      the urinary tract via the production of specific virulence factors. Recently, a
      novel virulence determinant, Vat, was described for the prototypical
      uropathogenic E. coli strain CFT073. Vat is a member of the SPATE (serine
      protease autotransporters of the Enterobacteriaceae) subfamily of the
      autotransporters. Previously, SPATEs have been described for all pathovars of E.
      coli, but until recently their presence had been noticeably absent in
      nonpathogenic E. coli. In this report we describe the prevalence and phylogenetic
      distribution of the SPATEs among uropathogenic E. coli and the ECOR collection,
      demonstrating an association between the presence of the SPATEs, including Vat,
      and uropathogenic E. coli phylogroups. In addition, we describe the distribution
      of SPATEs among nonpathogenic E. coli.

PMID- 16081955
TI  - Genetic diversity among type emm28 group A Streptococcus strains causing invasive
      infections and pharyngitis.
AB  - Genome sequencing of group A Streptococcus (GAS) has revealed that prophages
      account for the vast majority of gene content differences between strains.
      Serotype M28 strains are a leading cause of pharyngitis and invasive infections,
      but little is known about genetic diversity present in natural populations of
      these organisms. To study this issue, population-based samples of 568 strains
      from Ontario, Canada; Finland; and Houston, Texas, were analyzed. Special
      attention was given to analysis of variation in prophage-encoded virulence gene
      content by a PCR-based method. Thirty and 29 distinct prophage-encoded virulence
      gene profiles were identified among pharyngitis and invasive infection isolates.
      Thirteen profiles, representing the majority of the strains, were shared between
      these two classes of isolates. Significant differences were observed in the
      frequency of occurrence of certain prophage toxin gene profiles and infection
      type. M28 strains are highly diverse in prophage-encoded virulence gene content
      and integration site, supporting the key concept that prophages are critical
      contributors to GAS genetic diversity and population biology. Nucleotide sequence
      variation in the emm gene (encodes M protein) was also examined. Only three
      allelic variants were identified in the hypervariable portion of the emm28 gene.
      All but one strain had the same inferred amino acid sequence in the first 100
      amino acids of the mature M28 protein. In contrast, size differences in the emm28
      gene and inferred protein due to variable numbers of C-terminal repeats were
      common. The presence of macrolide resistance genes (mefA, ermB, and ermTR) was
      analyzed by PCR, and less than 2% of the strains were positive.

PMID- 16081956
TI  - Pilot study to evaluate microarray hybridization as a tool for Salmonella
      enterica serovar Typhimurium strain differentiation.
AB  - In developed countries, Salmonella enterica subspecies 1 serovars Enteritidis and
      Typhimurium range among the most common causes of bacterial food-borne
      infections. The surveillance and typing of epidemic Salmonella strains are
      important tools in epidemiology. Usually, Salmonella enterica subspecies 1
      serovars are differentiated by serotyping for diagnostic purposes. Further
      differentiation is done by phage typing as well as molecular typing techniques.
      Here we have designed and evaluated a prototype DNA microarray as a tool for
      serovar Typhimurium strain differentiation. It harbors 83 serovar Typhimurium
      probes obtained by differential subtractive hybridization and from the public
      database. The microarray yielded reproducible hybridization patterns in repeated
      hybridizations with chromosomal DNA of the same strain and could differentiate
      five serovar Typhimurium reference strains (DT204, DT104, DT208, DT36, and LT2).
      Furthermore, the microarray identified two distinct groups among 13 serovar
      Typhimurium DT104 strains. This correlated with observations from pulsed-field
      gel electrophoresis analysis. Twenty-three further serovar Typhimurium strains
      were analyzed to explore future directions for optimization of the simple 83
      probe DNA microarray. The data presented here demonstrate that DNA microarrays
      harboring small numbers of selected probes are promising tools for serovar
      Typhimurium strain typing.

PMID- 16081957
TI  - Phenotypic and molecular characterization of Candida nivariensis sp. nov., a
      possible new opportunistic fungus.
AB  - The new species Candida nivariensis, isolated from the clinical samples of three
      patients in Spain over a 3-year period, is presented here. This species can be
      easily differentiated from Candida glabrata, the closest genetic species, by
      different colony color on CHROMagar and by its ability to ferment trehalose. The
      analyses of the internal transcribed spacer region and the D1-D2 region of the
      26S rRNA gene sequences support a new species designation.

PMID- 16081958
TI  - Use of a novel panel of nine short tandem repeats for exact and high-resolution
      fingerprinting of Aspergillus fumigatus isolates.
AB  - Here we describe a new panel of short tandem repeats (STRs) for a novel exact
      typing assay that can be used to discriminate between Aspergillus fumigatus
      isolates. A total of nine STR markers were selected from available genomic A.
      fumigatus sequences and were divided into three multicolor multiplex PCRs. Each
      multiplex reaction amplified three di-, tri-, or tetranucleotide repeats,
      respectively. All nine STR markers were used to analyze 100 presumably unrelated
      A. fumigatus isolates. For each marker, between 11 and 37 alleles were found in
      this population. One isolate proved to be a mixture of at least two different
      isolates. With the remaining 99 isolates, 96 different fingerprinting profiles
      were obtained. The Simpson's diversity index for the individual markers ranged
      from 0.77 to 0.97. The diversity index for the multiplex combination of di-, tri
      , and tetranucleotide repeats ranged from 0.9784 to 0.9968. The combination of
      all nine markers yielded a Simpson's diversity index of 0.9994, indicative of the
      high discriminatory power of these new loci. In theory, this panel of markers is
      able to discriminate between no less than 27 x 10(9) different genotypes. The
      multicolor multiplex approach allows large numbers of markers to be tested in a
      short period of time. The exact nature of the assay combines high reproducibility
      with the easy exchange of results and makes it a very suitable tool for large
      scale epidemiological studies.

PMID- 16081959
TI  - Simultaneous detection of four human pathogenic microsporidian species from
      clinical samples by oligonucleotide microarray.
AB  - Microsporidian species have been rapidly emerging as human enteric pathogens in
      immunocompromised and immunocompetent individuals in recent years. Routine
      diagnostic techniques for microsporidia in clinical laboratories are laborious
      and insensitive and tend to underestimate their presence. In most instances, they
      are unable to differentiate species of spores due to their small sizes and
      similar morphologies. In this study, we report the development of another
      protozoan oligonucleotide microarray assay for the simultaneous detection and
      identification to the species level of four major microsporidian species:
      Enterocytozoon bieneusi, Encephalitozoon cuniculi, Encephalitozoon hellem, and
      Encephalitozoon intestinalis. The 18S small-subunit rRNA gene was chosen as the
      amplification target, labeled with fluorescence dye, and hybridized to a series
      of species-specific oligonucleotide probes immobilized on a microchip. The
      specificity and sensitivity of the microarray were clearly demonstrated by the
      unique hybridization profiles exhibited by each species of microsporidian tested
      and its ability to detect as few as 10 spores. In order to assess the
      applicability of this microarray in a clinical setting, we conducted microarray
      assays of 20 fecal samples from AIDS patients. Twelve of these samples were
      positive for the presence of microsporidia and could be confidently identified;
      11 of them were positive for more than one species. Our results suggested that
      this microarray-based approach represents an attractive diagnostic tool for high
      throughput detection and identification of microsporidian species in clinical and
      epidemiological investigations.

PMID- 16081960
TI  - Prolonged outbreak of infection due to TEM-21-producing strains of Pseudomonas
      aeruginosa and enterobacteria in a nursing home.
AB  - Over a 6-year period, 24 extended-spectrum beta-lactamase (ESBL)-producing
      isolates of Pseudomonas aeruginosa were collected from 18 patients living in a
      nursing home. These isolates had a delayed development of a red pigment and
      exhibited a similar antibiotype (resistance to all beta-lactams except for
      imipenem and to gentamicin, tobramycin, netilmicin, ciprofloxacin, and rifampin)
      associated with the production of the TEM-21 beta-lactamase and a type II 3'-N
      aminoglycoside acetyltransferase [AAC(3)-II] enzyme. Surprisingly, serotyping
      showed that these isolates belonged to four successive serotypes (P2, P16, P1,
      and PME), although molecular typing by PCR methods and pulsed-field gel
      electrophoresis yielded identical or similar profiles. Moreover, in all isolates
      the bla(TEM-21) gene was part of a chromosomally located Tn801 transposon
      truncated by an IS6100 element inserted within the resolvase gene, and the aac(3)
      II gene was adjacent to this structure. During the same period, 17 ESBL-producing
      isolates of enterobacteria were also collected from 10 of these patients. These
      isolates harbored a similar large plasmid that contained the bla(TEM-21) and the
      aac(3)-II genes and that conferred additional resistance to sulfonamides and
      chloramphenicol, as well as to kanamycin, tobramycin, netilmicin, and amikacin,
      conveyed by an AAC(6')-I enzyme. The bla(TEM-21) gene was part of the Tn801
      transposon disrupted by IS4321. Thus, a single clone of P. aeruginosa that had
      undergone a progressive genetic drift associated with a change in serotype
      appeared to be responsible for an outbreak of nosocomial infections in a nursing
      home. This strain has probably acquired the bla(TEM-21)-encoding plasmid that was
      epidemic among the enterobacteria at the institution, followed by chromosomal
      integration and genomic reorganization.

PMID- 16081961
TI  - Enhanced expression of an alpha2,6-linked sialic acid on MDCK cells improves
      isolation of human influenza viruses and evaluation of their sensitivity to a
      neuraminidase inhibitor.
AB  - The extensive use of neuraminidase (NA) inhibitors to treat influenza virus
      infections mandates close monitoring for resistant variants. Cultured cells do
      not provide a reliable means of evaluating the susceptibility of human influenza
      virus isolates to NA inhibitors. That is, the growth of such viruses in cell
      lines (e.g., Madin-Darby canine kidney [MDCK] cells) is not inhibited by these
      drugs, even though their sialidase activity is drug-sensitive. Matrosovich et al.
      (J. Virol. 77:8418-8425, 2003) showed that an MDCK cell line overexpressing the
      human beta-galactoside alpha2,6-sialyltransferase I (ST6Gal I) gene has the
      potential to assess the sensitivity of human influenza virus isolates to NA
      inhibitors, based on studies with a limited number of viruses. Here, we asked
      whether clinical isolates of influenza virus are universally sensitive to an NA
      inhibitor (oseltamivir) in an MDCK cell line expressing the ST6Gal I gene. The
      sensitivity of viruses to oseltamivir correlated with the sensitivity of viral
      sialidase to the compound, demonstrating the potential utility of this modified
      cell line for detecting NA inhibitor-resistant viruses. Moreover, in ST6Gal I
      overexpressing cells, the growth of human influenza viruses was up to 2 logs
      higher than in MDCK cells. We conclude that the human ST6Gal I-expressing MDCK
      cell line is useful not only for evaluating their sensitivity to NA inhibitors,
      but also for isolation of influenza viruses from clinical samples.

PMID- 16081962
TI  - Novel application of the masson-fontana stain for demonstrating Malassezia
      species melanin-like pigment production in vitro and in clinical specimens.
AB  - Melanin-like pigment produced in vitro and in vivo by Malassezia yeasts has not
      been described before. Masson-Fontana staining confirmed accumulation of black
      pigment on the cell walls of L-dihydroxyphenylalaline (L-DOPA)-cultured
      Malassezia species. Black pigment was also observed in cells and hyphae from
      hyperpigmented patient lesions with culture-confirmed pityriasis versicolor and
      seborrheic dermatitis.

PMID- 16081963
TI  - Photorhabdus asymbiotica, a pathogen emerging on two continents that proves that
      there is no substitute for a well-trained clinical microbiologist.
AB  - A 54-year-old ranch hand presented to the emergency room with an alleged spider
      bite and multiple abscesses. Both wound and blood cultures grew Photorhabdus
      asymbiotica, an enteric gram-negative rod that was initially misidentified by the
      hospital's rapid identification system. Clinical laboratories should be aware of
      the limitations of their rapid identification systems and always use them as an
      adjunct to analysis of morphological and phenotypic traits.

PMID- 16081964
TI  - Septic arthritis caused by vancomycin-intermediate Staphylococcus aureus.
AB  - Four methicillin-resistant Staphylococcus aureus isolates were consecutively
      isolated from synovial fluid and a knee wound of a patient with septic arthritis.
      Determination of the MIC of vancomycin and population analysis confirmed these
      isolates as vancomycin-intermediate S. aureus (VISA). Results of this study also
      revealed that cell wall thickness and reduced susceptibility to Triton X-100 were
      characteristic features of VISA.

PMID- 16081965
TI  - Oral Candida isolates colonizing or infecting human immunodeficiency virus
      infected and healthy persons in Mexico.
AB  - Oral yeast carriage was studied in 312 Mexican subjects. Candida albicans was the
      most frequent species, but other Candida spp. were isolated from 16.5 to 38.5% of
      patients. Colonization did not correlate with CD4+ number or viral load, but
      highly active antiretroviral therapy reduced the frequency of candidiasis. Most
      isolates were susceptible to fluconazole, but 10.8% were resistant to one or more
      azoles.

PMID- 16081966
TI  - Inhibitor-based methods for detection of plasmid-mediated AmpC beta-lactamases in
      Klebsiella spp., Escherichia coli, and Proteus mirabilis.
AB  - Non-beta-lactam inhibitor-based methods were evaluated for detecting plasmid
      mediated AmpC beta-lactamases in Klebsiella spp., Escherichia coli, and Proteus
      mirabilis. Using CLSI methodology and disks containing cefotetan alone and in
      combination with 400 mug of boronic acid, 9 of 10 positive control strains and 54
      of 55 AmpC-PCR-positive clinical isolates were detected. Importantly 71% and 40%
      of these clinical isolates were susceptible by routine testing to ceftriaxone and
      ceftazidime, respectively. Boronic acid disks also enhanced detection of expanded
      spectrum beta-lactamases in AmpC producers.

PMID- 16081967
TI  - Evaluation of beta-lactamase inhibitors in disk tests for detection of plasmid
      mediated AmpC beta-lactamases in well-characterized clinical strains of
      Klebsiella spp.
AB  - The diagnostic utility of the AmpC beta-lactamase inhibitors LN-2-128, 48-1220,
      and Syn 2190 in combination with cefotetan (CTT) or cefoxitin in a disk test for
      the detection of clinical isolates of Klebsiella spp. producing plasmid-mediated
      AmpC beta-lactamases (pAmpCs) was evaluated. The combination of Syn 2190 and CTT
      had a sensitivity of 91%, a specificity of 100%, and a reproducibility of 100%
      and showed the best potential of using an inhibitor for detection of Klebsiella
      spp. producing pAmpCs.

PMID- 16081968
TI  - Prevalence of herpes simplex virus (types 1 and 2), varicella-zoster virus,
      cytomegalovirus, and human herpesvirus 6 and 7 DNA in cerebrospinal fluid of
      Middle Eastern patients with encephalitis.
AB  - HSV-1 DNA was detected in 32 (30%) of 106 cerebrospinal fluid samples from
      patients with encephalitis. Cytomegalovirus, varicella-zoster virus, and human
      herpesvirus 6 (HHV-6) DNAs were each detected in three patients (3%); herpes
      simplex virus type 2 (HSV-2) and HHV-7 PCRs were negative. HSV detection was
      associated with seizure (P = 0.02), especially focal seizure (P = 0.0002), and
      pathological computed tomography (P = 0.02) with focal lesions (P = 0.0004).

PMID- 16081969
TI  - Reduced rate of diagnostic positive detection of JC virus DNA in cerebrospinal
      fluid in cases of suspected progressive multifocal leukoencephalopathy in the era
      of potent antiretroviral therapy.
AB  - Fifty-nine human immunodeficiency virus (HIV)-infected patients with suspected
      progressive multifocal leukoencephalopathy and 224 controls were tested for JC
      virus (JCV) DNA in cerebrospinal fluid by PCR. The diagnostic positive detection
      rate dropped from 89.5% (95% confidence intervals of 75.5 to 103.5%) in the pre
      highly active antiretroviral therapy (HAART) era to 57.5% (95% confidence
      intervals of 42.1 to 72.9%) in the HAART era; the specificity remained unchanged.
      Predictors of failure to detect JCV DNA were exposure to HAART at disease onset
      and higher CD4 counts.

PMID- 16081970
TI  - Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates.
AB  - A multilocus sequence typing (MLST) scheme was developed for Klebsiella
      pneumoniae. Sequences of seven housekeeping genes were obtained for 67 K.
      pneumoniae strains, including 19 ceftazidime- and ciprofloxacin-resistant
      isolates. Forty distinct allelic profiles were identified. MLST data were
      validated against ribotyping and showed high (96%) discriminatory power. The MLST
      approach provides unambiguous data useful for the epidemiology of K. pneumoniae
      isolates.

PMID- 16081971
TI  - Dissemination of CTX-M-type extended-spectrum beta-lactamase genes to unusual
      hosts.
AB  - A Citrobacter amalonaticus and a Morganella morganii producing the CTX-M-1
      extended-spectrum beta-lactamase (ESBL) were isolated from an area where this
      enzyme is now widespread in Escherichia coli. This is the first report of CTX-M-1
      in the former species. In both cases the ESBL determinant was possibly acquired
      by these unusual hosts in vivo, after coinfection with E. coli strains carrying
      conjugative plasmids encoding CTX-M-1.

PMID- 16081972
TI  - Comparison between sequence analysis and a line probe assay for testing genotypic
      resistance of human immunodeficiency virus type 1 to antiretroviral drugs.
AB  - The purpose of this study was to compare a line probe assay (LiPA) with sequence
      analysis for the detection of mutations conferring resistance to nucleoside and
      non-nucleoside inhibitors in human immunodeficiency reverse transcriptase and
      protease inhibitors. The limitations for interpreting LiPA make it unacceptable
      for routine clinical practice.

PMID- 16081973
TI  - Characterization of prolyl iminopeptidase-deficient Neisseria gonorrhoeae.
AB  - Prolyl iminopeptidase (PIP) is an enzyme produced by Neisseria gonorrhoeae, the
      detection of which is incorporated into several commercial test panels. In this
      report we describe two distinct mutations in the pip gene which account for the
      loss of PIP activity.

PMID- 16081974
TI  - Partial excision of the chromosomal cassette containing the methicillin
      resistance determinant results in methicillin-susceptible Staphylococcus aureus.
AB  - We report a detailed characterization of methicillin-susceptible Staphylococcus
      aureus isolates from five French hospitals negative for both the mecA and the
      ccrAB loci but positive for the IS431::pUB110::IS431::dcs structure, present in
      some Staphylococcus cassette chromosome mec (SCCmec) types. The presence of
      SCCmec-associated elements suggests that this unusual resistant phenotype is due
      to a partial excision of SCCmec from epidemic methicillin-resistant S. aureus.
      The hypothesis of a genetic relatedness is strengthened by common sequence and
      spa types and similar susceptibility patterns.

PMID- 16081975
TI  - Performance of a rapid immunochromatographic screening test for detection of
      antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2: experience
      at a tertiary care hospital in South India.
AB  - The performance characteristics of a rapid immunochromatographic-screening test,
      SD Bioline HIV-1/2 3.0 (Standard Diagnostics Inc., Kyonggi-do, South Korea) on
      23,754 sera and 30 plasma samples are reported. The sensitivity and specificity
      for the assay on serum samples are 100% and 99.4%, respectively. The assay
      detected antibodies in individuals infected with human immunodeficiency virus
      type 1 (HIV-1) genotypes A and C and HIV-2. This straightforward assay is a
      reliable diagnostic tool for screening HIV in resource-poor settings.

PMID- 16081976
TI  - Approaches to bacterial RNA isolation and purification for microarray analysis of
      Escherichia coli K1 interaction with human brain microvascular endothelial cells.
AB  - We established a protocol for isolation of microarray-grade bacterial RNA from
      Escherichia coli K1 interacting with human brain microvascular endothelial cells.
      The extracted RNA was free of human RNA contamination. More importantly,
      microarray analysis demonstrated that no bias was introduced in the gene
      expression pattern during the RNA isolation procedure.

PMID- 16081977
TI  - Affordable, abbreviated roche monitor assay for quantification of human
      immunodeficiency virus type 1 RNA in plasma.
AB  - The cost for the Roche Monitor assay kit can be reduced 50% by using only the
      1:1, 1:25, and 1:625 human immunodeficiency virus (HIV) and the 1:1 quantitation
      standard dilutions. This abbreviated test applied to 1,774 mostly African samples
      had results nearly identical to those obtained following the package insert
      instructions. To make this approach feasible, Roche would have to provide
      additional lysis buffer and master mix.

PMID- 16081978
TI  - Isolation and molecular typing of Naegleria fowleri from the brain of a cow that
      died of primary amebic meningoencephalitis.
AB  - Naegleria fowleri causes an acute and rapidly fatal central nervous system
      infection called primary amebic meningoencephalitis (PAM) in healthy children and
      young adults. We describe here the identification of N. fowleri isolated from the
      brain of one of several cows that died of PAM based on sequencing of the internal
      transcribed spacers, including the 5.8S rRNA genes.

PMID- 16081979
TI  - Use of the MGB Eclipse system and SmartCycler PCR for differentiation of
      Mycobacterium chelonae and M. abscessus.
AB  - Although accurate in the identification of Mycobacterium species, partial 16S
      rRNA gene sequencing does not distinguish Mycobacterium chelonae from M.
      abscessus. Thus, we designed a SmartCycler PCR assay targeting the 16S-to-23S
      internal transcribed spacer (ITS) region with use of MGB Eclipse probes to
      distinguish each species. Comparison with PCR-restriction enzyme analysis of a
      441-bp fragment of the hsp65 gene resulted in 100% correlation with 25 isolates
      of M. chelonae and 25 isolates of M. abscessus. ITS PCR performed on 90
      consecutive isolates identified by partial 16S rRNA gene sequencing (26 isolates
      of the M. chelonae-M. abscessus complex and 64 remaining isolates, including
      Mycobacterium species, Nocardia species, and other aerobic actinomycetes) showed
      100% specificity and sensitivity. The ITS PCR assay is accurate and specific,
      easy to perform, and a good supplemental test when using partial 16S rRNA gene
      sequencing to identify M. chelonae and M. abscessus.

PMID- 16081980
TI  - Dissemination of Salmonella enterica subsp. enterica Serovar Typhimurium var.
      Copenhagen clonal types through a contract heifer-raising operation.
AB  - Salmonella enterica subsp. enterica serovar Typhimurium var. Copenhagen isolates
      from a heifer-raising operation and from 11 dairy herds that had their calves
      contracted to the heifer-raising operation were examined for their phenotypic and
      genotypic characteristics. Results of the study showed that the heifer-raising
      operation could serve as a clearinghouse for Salmonella serovar Typhimurium var.
      Copenhagen and perhaps other Salmonella serotypes.

PMID- 16081981
TI  - Variation of the conserved neutralizing epitope in influenza B virus victoria
      group isolates in Japan.
AB  - For almost 20 years, the neutralizing-epitope site specific for influenza B virus
      Victoria group isolates was conserved at the "tip" of the hemagglutinin molecule;
      however, it was not detected in half of the isolates from the 2002-2003 epidemic
      in Japan. Amino acid substitutions (D164E or N165K) were observed at the "tip",
      and the epitope was altered. The viral antigenicities were affected, and human
      antibodies did not substantially inhibit the hemagglutination in the
      hemagglutination inhibition tests. It is suspected that such variants will be
      important in future epidemics.

PMID- 16081982
TI  - High seroprevalence of herpes simplex virus type 2 infection in French human
      immunodeficiency virus type 1-infected outpatients.
AB  - Using commercially available herpes simplex virus (HSV) type-specific serological
      diagnostic tests, HSV type 2 (HSV-2) antibody prevalence was assessed in two
      parallel prospective studies including 534 human immunodeficiency virus type 1
      (HIV-1)-infected outpatients living in two areas of northern France. In the first
      cohort of 434 subjects, 223 (51%) individuals demonstrated a positive HSV-2
      serological status while 66 (66%) of 100 subjects in the second cohort were
      seropositive for HSV-2 (51 versus 66%; P = 0.08). Among the 223 HSV-2
      seropositive subjects identified in the first study cohort, only 22 (10%) had
      suffered from recurrent anogenital lesions during the past 12 months while 154
      (69%) had no clinical history of herpesvirus infection. Our findings demonstrate
      high proportions of subclinical and undiagnosed HSV-2 infection in HIV-1-infected
      individuals and suggest that HSV type-specific serological testing in the French
      HIV-1-infected subpopulation could be an efficient strategy to diagnose
      clinically asymptomatic HSV-2 infections.

PMID- 16081983
TI  - Decreased prevalence of virulence factors among ciprofloxacin-resistant
      uropathogenic Escherichia coli isolates.
AB  - Ciprofloxacin resistance was identified in 18% and 6% of consecutively collected,
      clinically significant urinary tract isolates of Escherichia coli from inpatients
      and outpatients, respectively. In comparison to ciprofloxacin-susceptible
      isolates, there were fewer resistant isolates that expressed beta-hemolysis
      (outpatient, 9% versus 87%, P < 0.0001; inpatient, 4% versus 76%, P < 0.0001) and
      that had a papEF genotype, genes encoding P fimbriae (outpatient, 30% versus 70%,
      P = 0.0004; inpatient, 26% versus 70%, P < 0.0001).

PMID- 16081984
TI  - Genetic diversity of Campylobacter sp. isolates from retail chicken products and
      humans with gastroenteritis in Central Michigan.
AB  - Multilocus sequencing was used to compare Campylobacter sp. strains isolated from
      retail chicken products and humans with gastroenteritis in central Michigan.
      Sequence comparisons demonstrated overlapping diversity between chicken and human
      isolates. Campylobacter jejuni isolates from clinical sources had a greater
      diversity of flagellin alleles and a higher rate of quinolone resistance than
      isolates from retail chicken products.

PMID- 16081985
TI  - Molecular profiling and phenotype analysis of Escherichia coli O26:H11 and
      O26:NM: secular and geographic consistency of enterohemorrhagic and
      enteropathogenic isolates.
AB  - Fifty-eight enterohemorrhagic Escherichia coli O26:H11 or O26:NM (nonmotile)
      strains and 44 atypical enteropathogenic E. coli O26:H11 or O26:NM strains
      isolated from patients in 11 countries during 52 years share a common pool of non
      stx virulence genes, fitness loci, and genotypic and phenotypic diagnostic
      markers. These findings indicate close relatedness between these pathotypes and
      provide a basis for their clinical laboratory diagnosis.

PMID- 16081986
TI  - Monoclonal antibody routinely used to identify avirulent strains of Newcastle
      disease virus binds to an epitope at the carboxy terminus of the hemagglutinin
      neuraminidase protein and recognizes individual mesogenic and velogenic strains.
AB  - Newcastle disease virus (NDV) strains are classified as having high (velogenic),
      intermediate (mesogenic), or low (lentogenic) pathogenesis and virulence in
      chickens. Recent studies have established that the hemagglutinin-neuraminidase
      (HN) protein plays an important role in viral tropism and virulence. A monoclonal
      antibody (AVS-I) has previously been shown to be specific for lentogenic strains
      of NDV (Srinivasappa et al., Avian Dis. 30:562-567, 1986) and is routinely used
      to identify these strains. We have used competition antibody binding assays with
      a previously characterized panel of monoclonal antibodies, binding to chimeric HN
      proteins, and the characterization of an escape mutant to localize the binding
      site of AVS-I to the extreme carboxy terminus of the protein. In addition, we
      have shown that AVS-I does recognize at least one mesogenic strain and one
      velogenic strain of the virus, calling into question the potential of this
      antibody as a diagnostic reagent for avirulent NDV strains.

PMID- 16081987
TI  - Improved sensitivity of human immunodeficiency virus type 2 subtype B plasma
      viral load assay.
AB  - We developed a new assay for human immunodeficiency virus type 2 plasma RNA
      quantification based on a previous format. The new version performed
      significantly better than the original regarding the detection of subtype B,
      allowing the detection of 14 out of 36 plasma RNAs in the subtype B-infected
      patients not detected with the original version.

PMID- 16081988
TI  - Pathogen evolution in vivo: genome dynamics of two isolates obtained 9 years
      apart from a duodenal ulcer patient infected with a single Helicobacter pylori
      strain.
AB  - The survival and microevolution of Helicobacter pylori strains in the niches of
      the stomach after eradication therapy have largely been unexplored. We analyzed
      genomic signatures for two successive isolates obtained 9 years apart from a
      duodenal ulcer patient who underwent eradication therapy for H. pylori. These
      isolates were genotyped based on 50 different parameters involving three
      different fingerprinting approaches and several evolutionarily significant and
      virulence-associated landmarks in the genome, including nine informative gene
      loci, the cag pathogenicity island and its right junction, members of the
      plasticity region cluster, and vacA and iceA alleles. Our observations reveal
      that the two isolates were derived from the same strain that colonized the
      patient for almost a decade and were almost identical. Microevolution, however,
      was observed in the cagA gene and its right junction, the vacA m1 allele, and a
      member of the plasticity region cluster (JHP926). These results suggest that H.
      pylori has a great ability to survive and reemerge as a microevolved strain
      posteradication, thereby hinting at the requirement for follow-up of patients
      after therapy.

PMID- 16081989
TI  - Evaluation of two new chromogenic media, CHROMagar MRSA and S. aureus ID, for
      identifying Staphylococcus aureus and screening methicillin-resistant S. aureus.
AB  - Thirty-nine methicillin-resistant Staphylococcus aureus (MRSA) isolates with
      diverse genetic backgrounds and two reference strains were correctly identified
      as S. aureus on CHROMagar MRSA and S. aureus ID media. Growth inhibition on
      CHROMagar MRSA was noted. A combination of cefoxitin disk and S. aureus ID was
      found suitable for rapid MRSA screening.

PMID- 16081990
TI  - Improved laboratory safety by decontamination of unstained sputum smears for acid
      fast microscopy.
AB  - Tubercle bacilli may survive in unstained heat-fixed sputum smears and may be an
      infection risk to laboratory staff. We compared the effectiveness of 1% and 5%
      sodium hypochlorite, 5% phenol, 2% glutaraldehyde, and 3.7% formalin in killing
      Mycobacterium tuberculosis present in smears prepared from 51 sputum samples. The
      smears were decontaminated by the tube and slide techniques. Phenol at 5%,
      glutaraldehyde at 2%, and buffered formalin at 3.7% for 1 min (tube technique) or
      for 10 min (slide technique) were effective in decontaminating sputum smears and
      preserved cell morphology and quantitative acid-fast microscopy results.

PMID- 16081991
TI  - Stability of human immunodeficiency virus type 1 proviral DNA in whole-blood
      samples.
AB  - The Roche Amplicor HIV-1 Test requires that whole blood be processed within four
      days of collection. However, this requirement may be too limiting for use in
      international settings. Thus, we demonstrate that blood may be processed up to 10
      days after collection if maintained under ambient conditions (2 to 25 degrees C).

PMID- 16081992
TI  - Dynamic range and reproducibility of hepatitis B virus (HBV) DNA detection and
      quantification by Cobas Taqman HBV, a real-time semiautomated assay.
AB  - The Cobas Taqman assay for hepatitis B virus (HBV) DNA showed linear detection
      over 7 logs for genotypes A to D. The coefficient of variation was 1.2% at > or
      =1,000 IU/ml and 22.0% at 10 IU/ml. In 97 clinical samples, the log HBV DNA/ml
      differed by 0.11 between Cobas Amplicor and Cobas Taqman (r2 = 0.97).

PMID- 16081993
TI  - Primers for clinical detection of Paracoccidioides brasiliensis.
AB  - From a 0.72-kb fragment universally generated in Paracoccidioides brasiliensis
      strains, primers were designed and tested on genomic DNA of this and other
      pathogenic fungi. They were specific and highly sensitive for P. brasiliensis
      DNA. Positive results were obtained when these were tested in clinical samples.

PMID- 16081994
TI  - Microbiology of Bartholin's gland abscess in Japan.
AB  - This study was conducted to determine the current epidemiology concerning the
      causative organisms for Bartholin's gland abscess in Japan. Microbiological
      examination of 224 cases showed positive results in 219 cases and negative
      results in 5 cases. Of all of the bacterial isolates, 307 and 118 were aerobes
      and anaerobes, respectively. The most frequently isolated bacterium was
      Escherichia coli. Of the anaerobes, the most frequently isolated organism was
      Bacteroides species, followed by Prevotella species. The organisms related to
      respiratory infectious diseases, such as Streptococcus pneumoniae and Haemophilus
      influenzae, including resistant bacteria, were sometimes involved between 2000
      and 2004.

PMID- 16081995
TI  - Performance of single-step gel-based reverse transcription-PCR (RT-PCR) assays
      equivalent to that of real-time RT-PCR assays for detection of the severe acute
      respiratory syndrome-associated coronavirus.
AB  - Simple gel-based one-step reverse transcription-PCR (RT-PCR) assays, used to
      investigate patients during the 2003 severe acute respiratory syndrome (SARS)
      outbreak in Singapore, were found to be as sensitive as commercial and in-house
      real-time RT-PCR assays. The detection limit was approximately 1 genome
      equivalent (GE) per 5 microl PCR mixture. One PFU of SARS coronavirus was
      estimated to be 258 +/- 46 GE.

PMID- 16081996
TI  - Phenotypic and genotypic mupirocin resistance among Staphylococci causing
      prosthetic joint infection.
AB  - Mupirocin MICs and mupA presence were determined in 108 staphylococci causing
      prosthetic joint infection. Zero of 35 isolates (0%) of methicillin-susceptible
      Staphylococcus aureus, 4/15 (27%) methicillin-resistant S. aureus isolates, 3/16
      (19%) methicillin-susceptible coagulase-negative staphylococci, and 11/42 (26%)
      methicillin-resistant coagulase-negative staphylococci were mupirocin resistant.
      mupA was detected in all five high-level mupirocin-resistant staphylococci and
      one mupirocin-susceptible staphylococcus.

PMID- 16081997
TI  - Molecular detection of Cellulosimicrobium cellulans as the etiological agent of a
      chronic tongue ulcer in a human immunodeficiency virus-positive patient.
AB  - Ulcerations appeared on the tongue of a 48-year-old human immunodeficiency virus
      positive man. Histological findings of the biopsy specimen and the fact that the
      patient had resided in Louisiana led us to suspect "American histoplasmosis". A
      new ulcer appeared while the patient was being treated with itraconazole, and the
      gene for 16S rRNA of Cellulosimicrobium cellulans was amplified. The lesions
      healed during treatment with oral penicillin and azithromycin.

PMID- 16081998
TI  - Long-term respiratory tract infection with canine-associated Pasteurella dagmatis
      and Neisseria canis in a patient with chronic bronchiectasis.
AB  - Pasteurella dagmatis and Neisseria canis were repeatedly isolated from the sputum
      of a poodle-owning patient with chronic bronchiectasis. Commercially available
      systems failed to identify these unusual organisms: identification was made by
      16S rRNA gene sequencing. Difficulties identifying these and five other canine
      associated isolates (P. dagmatis [n = 2], Pasteurella canis [n = 2], and N. canis
      [n = 1]) are discussed.

PMID- 16081999
TI  - Streptococcus anginosus-associated endogenous endophthalmitis mimicking fungal
      endophthalmitis.

PMID- 16082000
TI  - Fatal family outbreak of Bacillus cereus-associated food poisoning.
AB  - Bacillus cereus is a well-known cause of food-borne illness, but infection with
      this organism is not commonly reported because of its usually mild symptoms. A
      fatal case due to liver failure after the consumption of pasta salad is described
      and demonstrates the possible severity of the emetic syndrome.

PMID- 16082001
TI  - First case of infant botulism caused by Clostridium baratii type F in California.
AB  - In late 2003 a severely hypotonic neonate, just 38 h old at onset of illness, was
      found to have infant botulism caused by neurotoxigenic Clostridium baratii type
      F. Environmental investigations failed to identify a source of this strain. This
      is the youngest patient reported to have infant botulism and the fifth instance
      of infant botulism caused by C. baratii type F.

PMID- 16082002
TI  - Pulmonary Mycobacterium sherrisii infection in a human immunodeficiency virus
      type 1-infected patient.
AB  - We report the first case of a pulmonary infection with Mycobacterium sherrisii in
      a patient with advanced human immunodeficiency virus infection. Mycobacterium
      sherrisii is a newly described nontuberculous mycobacterium related to
      Mycobacterium simiae. Sequencing of the 16S rRNA gene was used for species
      identification. Treatment and antibiotic susceptibilities are described.

PMID- 16082003
TI  - Infections due to the newly described species Mycobacterium parascrofulaceum.
AB  - We report on four cases of infection by the recently described species
      Mycobacterium parascrofulaceum. In two cases the mycobacterium was isolated from
      AIDS patients, while in the others it was responsible for pulmonary disease in
      elderly men. Our findings suggest that M. parascrofulaceum is an opportunistic
      pathogen, like many other nontuberculous mycobacterial species.

PMID- 16082004
TI  - Peritonitis due to Curvularia inaequalis in an elderly patient undergoing
      peritoneal dialysis and a review of six cases of peritonitis associated with
      other Curvularia spp.
AB  - Fungal peritonitis due to Curvularia species in patients undergoing peritoneal
      dialysis is a very rare problem. We report a case of peritonitis caused by
      Curvularia inaequalis. This is the first report in the English literature of this
      species causing human infection. We also review the six previously reported cases
      of continuous ambulatory peritoneal dialysis peritonitis caused by other
      Curvularia species.

PMID- 16082005
TI  - Clindamycin-resistant Fusobacterium varium bacteremia and decubitus ulcer
      infection.
AB  - Bacteremia due to Fusobacterium spp. is unusual (<10% of cases of anaerobic
      bacteremia), and the isolation of Fusobacterium varium is especially uncommon.
      The most probable sources of Fusobacterium bacteremia are the respiratory, the
      gastrointestinal, and the genitourinary tracts. A.-M. Bourgault et al. (Clin.
      Infect. Dis. 25[Suppl. 2]:181-183) described 40 patients with Fusobacterium
      bacteremia; only 3 had Fusobacterium varium, and no one had decubitus scars as
      the portal of entry. In another published series (S. Henry, A. De Maria, and W.
      R. McCabe, Am. J. Med. 75:225-231, 1983) of 26 cases, two patients had
      concomitant pulmonary lesions and decubitus ulcers but there was no
      identification to the species level mentioned. We report a case of Fusobacterium
      varium bacteremia and infected sacral decubitus ulcer in an elderly patient.

PMID- 16082006
TI  - Nonfermenters under the influence: ethanol disinfection of a saline dispenser
      caused misidentification by the Vitek 2 system using the new GN cards.

PMID- 16082007
TI  - Correctly identifying the streptothricin resistance gene cassette.

PMID- 16082008
TI  - Detection of five novel CTX-M-type extended spectrum beta-lactamases with one to
      three CTX-M-14 point mutations in isolates from Hefei, Anhui province, China.

PMID- 16082009
TI  - Liquid Granada medium for detection of group B streptococci.

PMID- 16082010
TI  - Tularemia, lawn mowers, and rabbits' nests.

PMID- 16082011
TI  - Japanese spotted fever in Korea.

PMID- 16082012
TI  - BioMart and Bioconductor: a powerful link between biological databases and
      microarray data analysis.
AB  - biomaRt is a new Bioconductor package that integrates BioMart data resources with
      data analysis software in Bioconductor. It can annotate a wide range of gene or
      gene product identifiers (e.g. Entrez-Gene and Affymetrix probe identifiers) with
      information such as gene symbol, chromosomal coordinates, Gene Ontology and OMIM
      annotation. Furthermore biomaRt enables retrieval of genomic sequences and single
      nucleotide polymorphism information, which can be used in data analysis. Fast and
      up-to-date data retrieval is possible as the package executes direct SQL queries
      to the BioMart databases (e.g. Ensembl). The biomaRt package provides a tight
      integration of large, public or locally installed BioMart databases with data
      analysis in Bioconductor creating a powerful environment for biological data
      mining.

PMID- 16082013
TI  - Impact modeling of gymnastic back-handsprings and dive-rolls in children.
AB  - This study was to determine estimates of the stiffness and damping properties of
      the wrist, and shoulder in children by examining wrist impacts on the
      outstretched hand in selected gymnastic activities. The influence of age, mass,
      and wrist and torso impact velocity on the stiffness and damping properties were
      also examined. Fourteen young gymnasts (ages 8 to 15 yrs) were videotaped while
      performing back-handspring trials or dive-rolls. Kinematic and ground reaction
      analysis provided input for computer simulation of the body as a rheological
      model with appropriate stiffness and damping. A significant positive linear
      relationship was obtained between wrist damping in dive rolls and age, mass, and
      wrist and torso impact velocity, while shoulder damping in the back-handsprings
      had a significant positive linear relationship with body mass. This new
      information on stiffness and damping at the shoulder and the wrist in children
      enables realistic mathematical modeling of children's physical responses to hand
      impact in falls. This is significant because modeling studies can now be used as
      an alternative to epidemiological studies to evaluate measures aimed at reducing
      injuries in gymnastics and other activities involving impact to the upper
      extremity.

PMID- 16082014
TI  - Comparison of elasticity of human tendon and aponeurosis in knee extensors and
      ankle plantar flexors in vivo.
AB  - The purposes of this study were to compare the elasticity of tendon and
      aponeurosis in human knee extensors and ankle plantar flexors in vivo and to
      examine whether the maximal strain of tendon was correlated to that of
      aponeurosis. The elongation of tendon and aponeurosis during isometric knee
      extension (n = 23) and ankle plantar flexion (n = 22), respectively, were
      determined using a real-time ultrasonic apparatus, while the participants
      performed ramp isometric contractions up to voluntary maximum. To calculate the
      strain values from the measured elongation, we measured the respective length of
      tendon and aponeurosis. For the knee extensors, the maximal strain of aponeurosis
      (12.1 +/- 2.8 %) was significantly greater than that of the patella tendon (8.3
      +/- 2.4 %), p < 0.001. On the contrary, the maximal strain of Achilles tendon
      (5.9 +/- 1.4 %) was significantly greater than that of aponeurosis in ankle
      plantar flexors (2.7 +/- 1.4 %), p < 0.001. Furthermore, for both knee extensors
      and ankle plantar flexors there was no significant correlation between maximal
      strain of tendon and aponeurosis. These results would be important for
      understanding the different roles of tendon and aponeurosis during human
      movements and for more accurate muscle modeling.

PMID- 16082015
TI  - Gender differences in lower extremity coupling variability during an
      unanticipated cutting maneuver.
AB  - The purpose of this study was to determine if gender differences exist in the
      variability of various lower extremity (LE) segment and joint couplings during an
      unanticipated cutting maneuver. 3-D kinematics were collected on 24 college
      soccer players (12 M, 12 F) while each performed the cutting maneuver. The
      following intralimb couplings were studied: thigh rotation (rot)/leg rot; thigh
      abduction-adduction/leg abd-add; hip abd-add/knee rot; hip rot/knee abd-add; knee
      flexion-extension/knee rot; knee flx-ext/hip rot. A vector-coding technique
      applied to angle-angle plots was used to quantify the coordination of each
      coupling. The average between-trial standard deviation of the coordination
      pattern during the initial 40 % of stance was used to indicate the coordination
      variability. One-tailed t-tests were used to determine differences between
      genders in coordination variability for each coupling. Women had decreased
      variability in four couplings: 32 % less thigh rot/leg rot variability; 40 % less
      thigh abd-add/leg abd-add variability; 46 % less knee flx-ext/knee rot
      variability; and 44 % less knee flx-ext/hip rot variability. These gender
      differences in LE coordination variability may be associated with the increased
      incidence of ACL injury in women. If women exhibit less flexible coordination
      patterns during competition, they may be less able to adapt to the environmental
      perturbations experienced during sports. These perturbations applied to a less
      flexible system may result in ligament injury.

PMID- 16082016
TI  - Characterization of a system for studying human gait during slope walking.
AB  - Sloped walking surfaces provide a unique environment for examining the
      biomechanics and neural control of locomotion. While sloped surfaces have been
      used in a variety of studies in recent years, the current literature provides
      little if any discussion of the integrity, i.e., validity, of the systems used to
      collect data. The goal of this study was to develop and characterize a testing
      system capable of evaluating the kinetics of human locomotion on sloped surfaces.
      A ramped walkway system with an embedded force plate was constructed and
      stabilized. Center of pressure and reaction force data from the force plate were
      evaluated at 6 ramp grades (0, 5, 15, 25, 35, and 39 %). Ground reaction force
      data at 0 % grade were effectively the same as data from the same force plate
      when mounted in the ground and were well within the range of intrasubject
      variability. Collectively, data from all tests demonstrate the fidelity of this
      ramp system and suggest it can be used to evaluate human locomotion over a range
      of slope intensities.

PMID- 16082017
TI  - A simple method for measuring stiffness during running.
AB  - The spring-mass model, representing a runner as a point mass supported by a
      single linear leg spring, has been a widely used concept in studies on running
      and bouncing mechanics. However, the measurement of leg and vertical stiffness
      has previously required force platforms and high-speed kinematic measurement
      systems that are costly and difficult to handle in field conditions. We propose a
      new "sine-wave" method for measuring stiffness during running. Based on the
      modeling of the force-time curve by a sine function,this method allows leg and
      vertical stiffness to be estimated from just a few simple mechanical parameters:
      body mass, forward velocity, leg length, flight time, and contact time. We
      compared this method to force-platform-derived stiffness measurements for
      treadmill dynamometer and overground running conditions, at velocities ranging
      from 3.33 m.s-1 to maximal running velocity in both recreational and highly
      trained runners. Stiffness values calculated with the proposed method ranged from
      0.67 % to 6.93 % less than the force platform method, and thus were judged to be
      acceptable. Furthermore, significant linear regressions (p < 0.01) close to the
      identity line were obtained between force platform and sine-wave model values of
      stiffness. Given the limits inherent in the use of the spring-mass model, it was
      concluded that this sine-wave method allows leg and stiffness estimates in
      running on the basis of a few mechanical parameters, and could be useful in
      further field measurements.

PMID- 16082018
TI  - The validity of summing lower extremity individual joint kinetic measures.
AB  - In the analysis of human movement, researchers often sum individual joint
      kinetics to obtain a single measure of lower extremity function. The extent to
      which these summed measures relate to the mechanical objectives of the task has
      not been formally validated. The criterion validity of these measures was
      established with comparisons to the mechanical objective of two multiple-joint
      tasks. For the Work task 18 participants performed a loaded barbell squat using 4
      resistances while instrumented for biomechanical analysis. For the Power they
      performed 2 predetermined amounts of work at both self-selected and fast speeds.
      Using inverse dynamics techniques, the peak net joint moment (PM) was calculated
      bilaterally in the sagittal plane at the ankle, knee, and hip and was summed into
      a single measure. This measure was correlated with the task objectives using
      simple linear regression. Similar procedures were used for the average net joint
      moment (AM), peak (PP), and average (AP) net joint moment power, and the net
      joint moment impulse (IM) and work (IP). For the Work task all 6 measures were
      significantly correlated with the task objective, but only AM, PM, and IP had
      correlation coefficients above 0.90. For the Power task, IM was not significantly
      correlated with the task objective, and only AP had a correlation coefficient
      above 0.90. These findings indicate that the validity of summing individual
      kinetic measures depends on both the measure chosen and the mechanical objective
      of the task.

PMID- 16082019
TI  - An ankle-foot orthosis powered by artificial pneumatic muscles.
AB  - We developed a pneumatically powered orthosis for the human ankle joint. The
      orthosis consisted of a carbon fiber shell, hinge joint, and two artificial
      pneumatic muscles. One artificial pneumatic muscle provided plantar flexion
      torque and the second one provided dorsiflexion torque. Computer software
      adjusted air pressure in each artificial muscle independently so that artificial
      muscle force was proportional to rectified low-pass-filtered electromyography
      (EMG) amplitude (i.e., proportional myoelectric control). Tibialis anterior EMG
      activated the artificial dorsiflexor and soleus EMG activated the artificial
      plantar flexor. We collected joint kinematic and artificial muscle force data as
      one healthy participant walked on a treadmill with the orthosis. Peak plantar
      flexor torque provided by the orthosis was 70 Nm, and peak dorsiflexor torque
      provided by the orthosis was 38 Nm. The orthosis could be useful for basic
      science studies on human locomotion or possibly for gait rehabilitation after
      neurological injury.

PMID- 16082020
TI  - Reliability of an individually molded shank shell for measuring tibial transverse
      rotations during the stance phase of walking.
AB  - Use of a shank shell has been shown to estimate tibial transverse rotations
      better than skin-mounted markers. However, the day-to-day reliability of the
      transverse tibial rotations using an individually molded shank shell has not been
      previously investigated. This study examined the between-tests and trials
      reliability of an individually molded shank shell for measuring peak tibial
      internal and external rotations, time of peak values, and tibia range of motion
      during 5 walking trials. The trial-to-trial reliability of tibial transverse
      rotations was measured in 14 healthy individuals while the test-retest
      reliability was measured in 10 persons on two occasions. Trial-to-trial
      reliability for peak transverse rotations, time of peak values, and tibia range
      of motion ranged from ICC (3,1) 0.59-0.95. The PCA between trials showed that 88
      99 % of values were within 3 degrees of agreement. Test-retest reliability for
      peak rotations, tibia range of motion, and time of peak values ranged from ICC
      (3,1) 0.70-0.89 with SEM 1.6-2.21 degrees , 0.021 %, and 0.034 %, respectively.
      The PCA between tests showed that 70-100 % of values were within 3 degrees of
      agreement. The use of an individually molded shell and the close attachment of
      the shank shell to the individual's shank resulted in reliable test-retest and
      trial-to-trial data.

PMID- 16082021
TI  - Biopharmaceutical proteins: opportunities and challenges.

PMID- 16082022
TI  - Expression of antibody fragments by periplasmic secretion in Escherichia coli.

PMID- 16082023
TI  - Secretory production of therapeutic proteins in Escherichia coli.

PMID- 16082024
TI  - Expression of recombinant LTB protein in Marine vibrio VSP60.

PMID- 16082025
TI  - Heterologous gene expression in yeast.

PMID- 16082026
TI  - Pharmaceutical proteins from methylotrophic yeasts.

PMID- 16082027
TI  - Expression of human papillomavirus type 16 L1 in baculovirus expression systems:
      a case study.

PMID- 16082028
TI  - Large-scale transient expression of therapeutic proteins in mammalian cells.

PMID- 16082029
TI  - Site-specific integration for high-level protein production in mammalian cells.

PMID- 16082030
TI  - Production of recombinant therapeutic proteins by mammalian cells in suspension
      culture.

PMID- 16082031
TI  - Transgene control engineering in mammalian cells.

PMID- 16082032
TI  - Fusion to albumin as a means to slow the clearance of small therapeutic proteins
      using the Pichia pastoris expression system: a case study.

PMID- 16082033
TI  - High-throughput recovery of therapeutic proteins from the inclusion bodies of
      Escherichia coli: an overview.

PMID- 16082034
TI  - Isolation, solubilization, refolding, and chromatographic purification of human
      growth hormone from inclusion bodies of Escherichia coli cells: a case study.

PMID- 16082035
TI  - Large-scale preparation of factor VIIa from human plasma: a case study.

PMID- 16082036
TI  - Purification of clinical-grade monoclonal antibodies by chromatographic methods.

PMID- 16082037
TI  - Virus elimination and validation.

PMID- 16082038
TI  - Virus removal by nanofiltration.

PMID- 16082039
TI  - Determining residual host cell antigen levels in purified recombinant proteins by
      slot blot and scanning laser densitometry.

PMID- 16082040
TI  - Principles of biopharmaceutical protein formulation: an overview.

PMID- 16082041
TI  - Solid-state protein formulation: methodologies, stability, and excipient effects.

PMID- 16082042
TI  - Stabilization of therapeutic proteins by chemical and physical methods.

PMID- 16082043
TI  - Extraction and characterization of vaccine antigens from water-in-oil adjuvant
      formulations.

PMID- 16082044
TI  - Probing reversible self-association of therapeutic proteins by sedimentation
      velocity in the analytical ultracentrifuge.

PMID- 16082045
TI  - Biological characterization of pegylated interferons: a case study.

PMID- 16082046
TI  - Characterization of interferon a2B pegylated via carboxyalkylation: a case study.

PMID- 16082047
TI  - Quantifying recombinant proteins and their degradation products using SDS-PAGE
      and scanning laser densitometry.

PMID- 16082048
TI  - Extraction and denaturing gel electrophoretic methodology for the analysis of
      yeast proteins.

PMID- 16082049
TI  - Characterization of therapeutic proteins by membrane and in-gel tryptic
      digestion.

PMID- 16082050
TI  - Oligosaccharide release and MALDI-TOF MS analysis of N-linked carbohydrate
      structures from glycoproteins.

PMID- 16082051
TI  - Capillary electrophoresis of carbohydrates derivatized with fluorophoric
      compounds.

PMID- 16082052
TI  - High-throughput LC/MS methodology for a(1-->3)Gal determination of recombinant
      monoclonal antibodies: a case study.

PMID- 16082053
TI  - Carbohydrate structural characterization of fas ligand inhibitory protein.

PMID- 16082054
TI  - Top-down characterization of protein pharmaceuticals by liquid
      chromatography/mass spectrometry: application to recombinant factor IX
      comparability- a case study.

PMID- 16082055
TI  - Sample preparation procedures for high-resolution nuclear magnetic resonance
      studies of aqueous and stabilized solutions of therapeutic peptides.

PMID- 16082056
TI  - Drug-drug interactions and the pharmacotherapy of HIV infection.
AB  - Knowledge of drug-drug interactions is crucial to HIV therapeutics. Recent
      reports in this area include reduced atazanavir exposure with coadministration of
      omeprazole or rifampin; increased hepatic toxicity with coadministration of
      saquinavir and rifampin; reduced buprenorphine exposure with concurrent efavirenz
      administration; absence of clinically significant interactions of
      depomedroxyprogesterone with nevirapine, efavirenz, or nelfinavir; increased
      atazanavir and saquinavir exposure with the double-boosted regimen of
      atazanavir/saquinavir/ritonavir; reduced amprenavir, lopinavir, and saquinavir
      exposure with the addition of tipranavir/ritonavir therapy; and reduced lopinavir
      and amprenavir exposure with the addition of fosamprenavir or
      fosamprenavir/ritonavir to lopinavir/ritonavir. This article summarizes a
      presentation on drug-drug interactions in HIV therapeutics by Angela D. M.
      Kashuba, PharmD, at the International AIDS Society-USA course in Los Angeles in
      April 2005.

PMID- 16082057
TI  - Metabolic complications of antiretroviral therapy.
AB  - HIV-infected patients receiving long-term antiretroviral treatment experience a
      number of metabolic abnormalities, including lipid abnormalities, dysregulation
      of glucose metabolism, body-fat redistribution, mitochondrial abnormalities, and
      bone abnormalities, as well as the sequelae of these disorders. These
      complications can be severe and life threatening, disrupt adherence to
      antiretroviral therapy, limit options in therapy, and profoundly affect quality
      of life. Risk for such complications should be considered in selection of
      antiretroviral therapy, and patients should be monitored for the occurrence of
      abnormalities and changes in risk factors. This article summarizes a presentation
      by Donna E. Sweet, MD, on the metabolic complications of long-term antiretroviral
      therapy at the IAS-USA course in New York in March 2005.

PMID- 16082058
TI  - Selected rare, noninfectious syndromes associated with HIV infection.
AB  - Infrequent and sometimes treatable noninfectious syndromes associated with HIV
      disease include tenofovir-associated Fanconi syndrome, a proximal renal tubular
      disorder; pulmonary hypertension that appears to be due to HIV-driven
      inflammation resulting in endothelial proliferation; thrombotic thrombocytopenic
      purpura, characterized by intravascular coagulopathy; diffuse infiltrative
      lymphocytosis syndrome, which can affect multiple organs; and Castleman's
      disease, a lymphoproliferative disorder that usually occurs in a multicentric
      form with poor prognosis in HIV-infected patients. This article summarizes a
      presentation on the characteristics, diagnosis, treatment, and prognosis of these
      disorders by Molly E. Eaton, MD, at the International AIDS Society-USA course in
      Atlanta in March 2005.

PMID- 16082059
TI  - Sex differences in the pharmacologic effects of antiretroviral drugs: potential
      roles of drug transporters and phase 1 and 2 metabolizing enzymes.
AB  - Sex differences in the pharmacologic effects of antiretroviral drugs are
      increasingly being reported. Emerging evidence suggests that women may be at
      increased risk of developing adverse effects of antiretroviral drugs. Several
      mechanisms have been proposed to explain sex differences in drug effects,
      including physiologic differences between men and women and the influence of sex
      hormones on drug metabolism. This article reviews sex-related variations in the
      levels of expression and activities of drug transporters and metabolizing enzymes
      involved in the disposition of the antiretroviral drugs, and postulates that
      these variations may partly explain sex differences in the responses to these
      drugs. Studies that explore relationships between levels of expression and
      activities of relevant enzymes and drug transporters and observed sex-related
      differences in treatment responses to antiretroviral drugs will help clarify the
      extent to which molecules involved in drug disposition affect sex differences in
      treatment response.

PMID- 16082060
TI  - Modern diagnostics of Chlamydia trachomatis infections.
AB  - Chlamydia trachomatis (C. trachomatis) is the most common agent of sexually
      transmitted infections. The clinical spectrum of the disease ranges from
      urethritis to infertility in women and to trachoma. Intracellular localisation of
      the pathogen creates a challenge for routine diagnostics. In this review possible
      diagnostic tests have been presented, varying from classic cell culture analysis
      and serodiagnostics (Enzyme-linked Immunoassays, Indirect Immunofluorescence) to
      the most sophisticated nucleic acid analyses (hybridisation, Polymerase Chain
      Reaction, Transcription Mediated Amplification, Ligase Chain Reaction),
      Advantages and disadvantages of the leading tests are discussed. Possible reasons
      of false positive as well as false negative results of genetic testing are
      presented.

PMID- 16082061
TI  - Chlamydia trachomatis infection in pregnant women hospitalised in the Institute
      of Mother and Child in Warsaw, Poland.
AB  - Chlamydia trachomatis infection is the most common sexually transmitted disease.
      It concerns both epidemiologists and clinicians as it is often asymptomatic and
      can cause permanent sequelae. Chlamydia trachomatis infection in women causes
      nongonococcal cervicitis, endometritis, urethritis, inflammation of the
      Bartholin's gland, acute and chronic pelvic inflammatory disease, Fitz-Hugh
      Curtis syndrome and can lead to Fallopian tube obstruction, infertility and
      ectopic pregnancy. During pregnancy it can cause chorioamnionitis, premature
      rupture of membranes, premature delivery, intrauterine growth restriction, low
      birth weight. post partum endometritis and also infection in the newborn. AIM: To
      assess the prevalence and to describe risk factors (behavioural and clinical) of
      genital infection caused by Chlamydia trachomatis in the population of pregnant
      women attending the Obstetrics Clinic at the Institute of Mother and Child and to
      study the impact of this infections of pregnancy outcome. METHODS: We have tested
      80 pregnant women attending the clinic of obstetrics and gynaecology of the
      Mother and Child Institute in Warsaw: The presence of C. trachomatis in cervical
      swabs was assessed using the Polymerase Chain reaction (PCR). RESULTS: We found
      two cases of C. trachomatis infection, which represents 2.5% of the tested
      population. CONCLUSIONS: controversial data on the prevalence of C. trachomatis
      in pregnant women and its influence on pregnancy duration justify further
      investigations despite the observed law prevalence in this study. This will allow
      to determine the role and usefulness of routine screening for C. trachomatis in
      pregnant women in Poland.

PMID- 16082062
TI  - The prevalence of Chlamydia trachomatis infection in pregnant women.
AB  - PURPOSE: The aim of our study was to estimate the prevalence of Chlamydia
      trachomatis infection, the risk factors, the impact of the infection on the
      course of pregnancy and the condition of neonates born from pregnancies
      complicated by Chlamydia trachomatis infection. MATERIALS AND METHODS: 558
      pregnant women aged 18-42 yrs, between the 4th and 40th week of pregnancy
      recruited from the Department of Obstetrics and Gynaecology, Medical Academy
      Lublin, and 10 men, partners of Chlamydia trachomatis infected patients were
      included in the study. All patients were examined using an immunoenzymatic method
      (MEIA). The ligase chain reaction (LCR) method was used only in cases of
      Chlamydia trachomatis detection with the use of MEIA method, in male partners of
      infected women and in patients with a cervical erosion and with a mucopurulent
      cervicitis. There were 64 women and 10 men who were examined using the LCR
      method. RESULTS: Positive results of MEIA test were found in 10 women (1.8% of
      studied population). Among men, the infection by Chlamydia trachomatis was
      present in 9 cases (90%). There were no infections with Chlamydia trachomatis in
      the group of neonates born from infected mothers. CONCLUSIONS: The prevalence of
      Chlamydia trachomatis infection was 1.8% in the studied group. The factors
      favourable for an infection are: young, unmarried patients, residents of towns or
      cities and changes in the cervix such as cervicitis or ectopy. In the cases of
      pathological pregnancy we should take into account Chlamydia trachomatis
      infections as a cause of abdominal pain or premature uterine contractions. The
      test towards Chlamydia trachomatis infection should be performed in pregnant
      patients to decrease the rate of pregnancy complications.

PMID- 16082063
TI  - Chlamydial infections in obstetrics and gynaecology in Israel.
AB  - Chlamydia trachomatis, an obligate intracellular bacterium, is the most frequent
      cause of sexually transmitted disease in the western countries. Similarly, among
      patients attending a sexually transmitted diseases clinic in Israel, the most
      prevalent pathogen found was Chlamydia trachomatis. The present review was aimed
      to evaluate the clinical significance of chlamydial infection during pregnancy
      and among gynaecological patients in Israel. A MEDLINE search using the key word
      "chlamydial infection" and "Israel" was performed. All relevant articles dealing
      with chlamydial infection in obstetrics and gynaecology were reviewed. Chlamydial
      infection during pregnancy is not rare and its incidence depends on the
      demographic structure of the population. Most parturients have sub-clinical or
      asymptomatic chlamydial infections during pregnancy. While controversy exists
      regarding the effects of maternal chlamydial infection on pregnancy outcome, no
      adverse pregnancy complications related to Chlamydia trachomatis were found in
      the Israeli studies. The majority of gynaecology patients with chlamydial
      infections were asymptomatic and the most significant clinical symptoms for
      chlamydial infections were purulent or mucoid discharge, bleeding and vaginitis.
      Further prospective studies are needed to investigate the prevalence of Chlamydia
      trachomatis in the general population and during pregnancy, in particular; in
      order to verify pregnancy outcome following chlamydial infections.

PMID- 16082064
TI  - The PCR assessed prevalence of Chlamydia trachomatis in aborted tissues.
AB  - BACKGROUND: Infections caused by Chlamydia trachomatis (ChT) are the most
      prevalent sexually transmitted bacterial infections worldwide. ChT is a cause of
      cervicitis, endometritis, salpingitis, tubal infertility and ectopic pregnancy.
      Perinatal infections with ChT have been associated with premature rupture of
      membranes, stillbirth, preterm delivery, and in newborns with conjunctivitis and
      pneumonia. There are controversial data referring to the association between
      colonisation by ChT and the risk of spontaneous abortion. Only few studies
      investigated the prevalence of ChT antigens in aborted tissues. AIM: To determine
      the prevalence of ChT in patients with spontaneous pregnancy loss using
      Polymerase Chain Reaction (PCR). MATERIALS AND METHOD: We completed prospective
      analysis of 50 patients after spontaneous abortions. The prevalence of ChT
      infections was assessed by PCR performed in samples taken during curettage
      following miscarriage. RESULTS: ChT was present in 16 (32%) of samples. Other
      pathogens of the lower genital tract were found in cultures from 11 patients.
      CONCLUSIONS: The prevalence of ChT infections in early abortions in this study
      was found to be surprisingly high. It implies the importance of screening of
      women planning pregnancy and pregnant women for this disease.

PMID- 16082065
TI  - Chlamydia trachomatis infections in women with adverse pregnancy outcome.
AB  - AIM: The aim of the study was to evaluate the prevalence of Chlamydia trachomatis
      (C. trachomatis) infection in women with adverse pregnancy outcomes. MATERIAL AND
      METHOD: 258 patients aged 18-43 yrs were enrolled into the study. Among them, 162
      women have had spontaneous abortions in the past (group A), 81 had history of
      intrauterine death of the foetus (group B) and 15 women had experienced preterm
      deliveries (group C). The control group (group D) included 131 women who were in
      the second or third trimester of uncomplicated pregnancy. C. trachomatis was
      investigated in cervical and urethral smears using direct immunofluorescence or
      Ligase chain reaction (LCR) for direct testing and immunoenzymatic assay (EIA)
      for serological testing and detection of specific IgG antibodies. RESULTS: C.
      trachomatis was detected in 25.9% patients in group A, 35.8% in group B and 20%
      in group C and only in 12.7% in group D. IgG specific antibodies were present in
      31.5%, 41.9%, 26.6% and 14.5% of patients in these groups respectively. The
      highest prevalence of chlamydial infections, regardless the diagnostic method
      used, was registered in the group of women with a history of 3 abortions (42.3%
      when direct testing and 45.5% when serological testing) while the lowest
      prevalence was in women who experienced only l abortion (23.2% and 28%).
      CONCLUSION: C. trachomatis infection in pregnancy affects its duration as it can
      lead to miscarriage, death of the foetus and preterm delivery.

PMID- 16082066
TI  - Chlamydia trachomatis infection in sexually active adolescents and young women.
AB  - BACKGROUND: The prevalence of Chlamydia trachomatis infections among Polish
      teenagers is unknown. Sexually active adolescents are at a greater risk for
      sexually transmitted infections, including Chlamydia trachomatis (ChT). Most
      inflections are asymptomatic and therefore untreated. Early detection and
      treatment of cervical chlamydial infections can prevent pelvic inflammatory
      disease and has a strong protective effect against infertility. AIM: To determine
      the prevalence and risk factors of Chlamydia trachomatis infections among
      sexually active female adolescents attending the outpatient gynaecological clinic
      of the Institute of Mother and Child in Warsaw. MATERIALS AND METHODS: 249
      sexually active girls, 16-19 years old, attending the outpatient clinic of the
      Institute of Mother and Child in Warsaw were enrolled in this study from December
      2002 to May 2004, The participants filled out a questionnaire containing
      informations on age, purpose of the visit, level of education, age of the first
      intercourse, number of lifetime sexual partners, number of current partners (in
      the last 3 months), number of sexual partners in the past (patients' partner),
      contraceptive methods, use of condoms at the first and the last intercourse, past
      history of STD and obstetric history at first visit. Pelvic examination was done
      for the following reasons: checking vaginal discharge, presence of abnormalities
      of the cervix such as ectopy, erythroplakia and uterine tenderness and taking a
      Pap smear and a cervical swab for Chlamydia trachomatis detection. Cervical swabs
      for Chlamydia trachomatis were tested by Polymerase Chain Reaction (PCR).
      RESULTS: The prevalence of ChT genital infection in the studied group was 3.2%.
      Adolescent females infected by ChT less frequently reported the use of condom and
      more often did not use any contraception in comparison with the girls without ChT
      genital infections (42.8% and 42.8% vs. 49% and 12.8%), The existence of other
      STDs was more frequently noted in adolescents with Chlamydial infection in
      comparison to healthy girls (14.2% vs. 8.3%). There were no statistically
      significant differences in results of the Pap smears and the incidence of
      cervical ectopy between the two groups.

PMID- 16082067
TI  - Chlamydia infections in the neonatal period.
AB  - The paper presents current knowledge about the clinical course, diagnostic and
      treatment of chlamydial infections in the neonatal period. In the neonatal
      period, infections caused by Chlamydia trachomatis are in the majority of
      maternal origin. Chlamydia mother to child transmission occurs during vaginal
      birth. It can also occur but rarely, during caesarean section after premature
      rupture of membranes. Chlamydia trachomatis infection of the genitourinary system
      in pregnancy increases the danger of intrauterine growth restriction and foetal
      death. It rises the perinatal morbidity of foetuses and newborns and increases
      the risk of premature deliveries. Chlamydia trachomatis infection in newborns
      manifests as conjunctivitis and ophthalmia and less commonly as pharyngitis and
      otitis media. Erythromycin is applied in prophylaxis and treatment of Chlamydia
      infections.

PMID- 16082068
TI  - Chlamydia trachomatis infections in children.
AB  - Based of literature data, the authors present informations on epidemiology,
      pathogenesis, clinical picture, diagnostics and treatment of Chlamydia
      trachomatis urogenital infections in children.

PMID- 16082069
TI  - The role of Chlamydia trachomatis infection in the development of cervical
      neoplasia and carcinoma.
AB  - This paper is a comparative analysis of several recent studies on the
      relationship between Chlamydia trachomatis infection and the development of
      cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. In the
      pathogenesis of cervical cancer, the role of Human Papillomavirus (HPV) is
      already well-documented; however, chronic Chlamydia trachomatis infection may
      have an indirect influence on the development of the disease.

PMID- 16082070
TI  - Subclinical prostatic inflammation attributable to Chlamydia trachomatis in a
      patient with prostate cancer.
AB  - Chronic inflammation has long been linked to cancers with an infectious etiology.
      Subclinical intraprostatic inflammation is a frequent finding in prostatic
      specimens obtained during surgical procedures. Recent studies using biomolecular
      (amplification) methods showed that the incidence of cryptic bacterial infections
      of prostate gland may be underestimated. We present the case of 66 years old man
      with no symptoms of prostatitis in whom chronic Chlamydia trachomatis infection
      was diagnosed based on the patient's medical history and detection of chlamydial
      DNA in prostate biopsy specimen by means of ligase chain reaction. Two years
      later the patient was diagnosed with prostate cancer on repeated prostate biopsy.

PMID- 16082071
TI  - Role of Chlamydia trachomatis in male urogenital infections and its
      complications.
AB  - Based on a literature review, the authors present data on the epidemiology,
      pathogenesis, clinical picture, diagnostics and treatment of Chlamydia
      trachomatis urogenital infections and its complications in males.

PMID- 16082072
TI  - Assessment of direct fluorescent antibody technique in detecting Chlamydia
      trachomatis in sexually transmitted infections clinics.
AB  - AIM: To compare Direct Fluorescent Antibody (DFA) test with Ligase Chain Reaction
      (LCR). MATERIALS AND METHODS: Urethral (in males) of cervical swabs, and samples
      of urine were obtained from 356 consecutive patients of the Institute of
      Venerology (220 males and 136 females). Among them there were 96 sexual couples.
      In 74 finally evaluated and analysed sexual couples at least one sample from one
      partner was positive in at least one performed test. RESULTS: LCR-urethra was
      positive in 60 out of 65 males while LCR-urine and DFA-urethra were positive in
      59 and 57 men respectively. CONCLUSION: Men infected with C. trachomatis were
      usually the first to seek medical care; their sex-partners come later. These
      findings suggest that DFA in males, which is only slightly less sensitive than
      LCR, should be recommended. Sex-partners of these men, symptomatic and
      asymptomatic, even with negative DFA-cervix should be given prophylactic
      treatment.

PMID- 16082073
TI  - Is it justifiable to perform screening tests for Chlamydia trachomatis in
      pregnant women?
AB  - Worldwide, Chlamydia trachomatis (CT) is the most common sexually transmitted
      bacteria. The improved understanding of CT pathophysiology in recent years became
      possible through DNA amplification technique and genome cloning. This paper
      updates informations on chlamydial infection in pregnant women, its
      pathophysiology, diagnostic methods, prevention and treatment. There is
      increasing evidence that Chlamydia trachomatis infection may result in a number
      of adverse pregnancy outcomes, including early and late abortion, infection of
      the foetus, stillbirth, premature rupture of membranes, prematurity and
      postpartum endometritis. Ectopic pregnancy is often associated with a previous
      tubal chlamydial infection. C. trachomatis infection in newborns may be acquired
      during pregnancy or during vaginal delivery, and it may result in neonatal
      conjunctivitis and/or pneumonia. We discuss benefits of early treatment of
      chlamydial infections in pregnant women and present guidelines for treatment.
      Screening should lead to early detection and treatment of men and women with
      chlamydial infection and thereby reduce the incidence of pelvic inflammatory
      disease, tubal infertility and ectopic pregnancy.

PMID- 16082074
TI  - D8/17 monoclonal antibody: an unclear neuropsychiatric marker.
AB  - OBJECTIVE: It has been hypothesized that monoclonal antibody D8/17 identifies a B
      lymphocyte antigen with expanded expression in patients with rheumatic fever,
      childhood onset obsessive-compulsive disorder (OCD), Tourette syndrome (TS) or
      prepubertal anorexia nervosa (AN). Our purpose was to replicate these studies in
      a Spanish population and to determine whether D8/17 identifies a subgroup of
      these patients, focusing especially on OCD subjects. METHOD: D8/17 expression was
      assessed with double immunofluorescence and flow cytometry using monoclonal
      immunoglobulin M (IgM) in three groups of patients with diagnoses of OCD (n =
      17), TS (n = 5) and prepubertal AN (n = 5), recruited during 2001. RESULTS: In
      the sample studied the average percentage of B cells expressing D8/17 was 4.8%.
      The D8/17 positive proportion of B lymphocytes was above 11% in only two out of
      17 OCD patients (7.4% of total sample) and in none of the TS or prepubertal AN
      patients. No statistically significant differences were found in mean percentages
      of D8/17 between the three groups. CONCLUSIONS: In the sample studied the
      expression of D8/17 in B cells was very low and the great majority of patients
      were negative for the D8/17 marker. The molecular characterization of D8/17 would
      be a major step forward in clarifying its implication for these diseases.

PMID- 16082075
TI  - Neuroleptic malignant syndrome: diagnostic and therapeutic dilemmas.
AB  - Neuroleptic malignant syndrome (NMS) is a life threatening medical state
      complicating the use of antipsychotic medications and other drugs that affect the
      dopaminergic system on administration or withdrawal. The condition was recognised
      nearly half a century ago, shortly after the discovery of antipsychotic
      medications. However, there are still no systematic studies about NMS. There are
      no definitive guidelines on its treatment. Although early recognition is
      emphasised and usually possible, delayed diagnosis is not rare. We here report on
      a case of NMS complicated by renal failure, and possibly respiratory failure. The
      report underscores the seriousness of delayed diagnosis and puts forward a
      comprehensive management recommendation based on our experience and the existing
      literature.

PMID- 16082076
TI  - Posterior cortical atrophy: clinical presentation and cognitive deficits compared
      to Alzheimer's disease.
AB  - BACKGROUND: Posterior cortical atrophy (PCA) is an uncommon dementia syndrome
      with initial manifestations of visual dysfunction and preservation of memory and
      language until late in the disease. Since prognosis and management differ from
      typical Alzheimer's disease (tAD), clinical tests to distinguish PCA from tAD are
      needed. METHODS: Fifteen PCA cases and 15 tAD cases, defined by clinical and MRI
      criteria, were compared by present symptoms and scores on four cognitive tests.
      RESULTS: Symptoms of visual disturbance and dyslexia were more commonly reported
      in PCA cases (p = 0.0001 and p = 0.006, respectively), and memory loss was more
      commonly reported in tAD (p = 0.006). Patients with PCA were less accurate on the
      Cortical Vision Screening Test (t = 6.0; p < 0.001) and in copying the Rey
      Osterreith Complex Figure (t = 6.0; p < 0.001), in comparison to the tAD group.
      Memory, evaluated by the Rey Auditory Verbal Learning Test, was impaired in both
      groups; however, delayed recall was more impaired in the tAD group (t = 2.5; p =
      0.03). CONCLUSION: Compared to patients with tAD, patients with PCA are more
      likely to present to their providers with symptoms of visual dysfunction.
      Performance on simple tests of visual perception and copying can be used to
      distinguish the two disorders even a few years after initial symptoms.

PMID- 16082077
TI  - Reaction time of motor responses in two-stimulus paradigms involving deception
      and congruity with varying levels of difficulty.
AB  - Deception research has focused on identifying peripheral nervous system markers
      while ignoring cognitive mechanisms underlying those markers. Cognitive theorists
      argue that the process of deception may involve such constructs as attentional
      capture, working memory load, or perceived incongruity with memory, while
      psychophysiologists argue for stimulus salience, arousal, and emotion. Three
      studies were conducted to assess reaction time (RT) in relation to deception,
      response congruity, and preparedness to deceive. Similar to a semantic
      verification task, participants evaluated sentences that were either true or
      false, and then made truthful or deceptive evaluations of the sentence's base
      truth-value. Findings indicate that deceptive responses have a longer RT than
      truthful responses, and that this relationship remains constant across response
      type and preparedness to deceive. The authors use these findings in preliminary
      support of a comprehensive cognitive model of deception.

PMID- 16082078
TI  - Stuttering due to ischemic stroke.
AB  - Acquired stuttering is a disorder of the fluency of speech. The mechanism
      underlying stuttering is unknown. It may occur after bilateral and unilateral
      cortical or subcortical brain damage. We report two cases who had stuttering
      resulting from left parietal infarction.

PMID- 16082079
TI  - Wheel-running modestly promotes functional recovery after a unilateral cortical
      lesion in rats.
AB  - BACKGROUND: We aimed to determine whether early or delayed wheel-running (W)
      after a cortical lesion in rats influences functional recovery and protein
      expression involving synaptic plasticity. METHODS: 57 rats were arranged in 4
      groups: (1) Sham, (2) NMDA, (3) W-24 h or (4) W-72 h (W-24 h and W-72 h means
      wheel-running for 14 days starting day 1 or day 3 after NMDA lesion). NMDA
      produced a standardized lesion in the unilateral sensorimotor cortex and
      detectable behavioral deficits. Synaptogenesis was measured by
      immunohistochemistry. RESULTS: Wheel-running starting after 24 h had no
      detectable effect, but it significantly speeded functional recovery when delayed
      to after 72 h. These results were in accordance with a marker linked to
      synaptogenesis. CONCLUSION: Wheel-running starting 3 days, but not 1 day, after
      an NMDA lesion is associated with improved functional recovery.

PMID- 16082080
TI  - FK506 and anti-CD40 ligand in peripheral nerve allotransplantation.
AB  - PURPOSE: Immunomodulatory agents are often combined in organ transplantation to
      minimize toxicity and enhance therapeutic effect. We hypothesized that combining
      low-dose FK506 with anti-CD40 Ligand (anti-CD40L mAb) would enhance regeneration
      through peripheral nerve allografts while preserving immune unresponsiveness.
      METHODS: Eighty Balb/cJ mice underwent tibial nerve grafting and were randomized
      to 10 groups treated with combinations of anti-CD40L mAb therapy, low-dose FK506
      (0.5 mg/kg/day), high-dose FK506 (2 mg/kg/day), and high-dose cyclosporine (25
      mg/kg/day). At 3 weeks, histomorphometry and cytokine secretion assays were
      performed. RESULTS: Animals receiving low-dose FK506 with anti-CD40L mAb
      exhibited robust nerve regeneration comparable to the isograft and high-dose
      FK506 allograft groups. Nerve density was significantly increased in the low-dose
      FK506 with anti-CD40L mAb group compared to animals receiving anti-CD40L mAb
      alone (p < 0.05). Combining anti-CD40L mAb with high dose cyclosporine decreased
      nerve fiber counts, nerve density, and percent nerve (p < 0.05). Interferon-gamma
      production was markedly elevated in untreated allografts compared to all other
      treatment groups (p < 0.05). Cytokine secretion was intermediate in the low-dose
      FK506 alone group and suppressed in all remaining groups. CONCLUSION: When
      combined with anti-CD40L mAb, low-dose FK506 enhances nerve regeneration without
      disrupting immune unresponsiveness.

PMID- 16082081
TI  - Dimeric fibroblast growth factor-2 enhances functional recovery after focal
      cerebral ischemia.
AB  - PURPOSE: The purpose of this study was to examine the effects of dimerized basic
      fibroblast growth factor (dFGF), a novel engineered growth factor, in a model of
      functional recovery following focal cerebral infarction (stroke) in rats.
      METHODS: A focal stroke was made in mature male rats by occlusion of the middle
      cerebral artery (MCA). dFGF was administered by intracisternal injection at one
      and three days after stroke. Tests to evaluate sensorimotor recovery of the
      contralateral limbs were done during the next three weeks after stroke. RESULTS:
      dFGF significantly enhanced recovery of sensorimotor function in limb placing and
      body swing tests compared to vehicle treatment. There were no differences in body
      weight or infarct volume in dFGF- vs. vehicle-treated animals. CONCLUSIONS: dFGF
      represents a potential treatment to enhance functional recovery after stroke and
      offers several advantages over bFGF, including stability and independence from
      extracellular heparan sulfates.

PMID- 16082082
TI  - Ischemic lesion volume correlates with long-term functional outcome and quality
      of life of middle cerebral artery stroke survivors.
AB  - PURPOSE: Previous studies investigating relationships between stroke lesion
      volume and outcome were restricted to short follow-up periods (3-6 months) and
      outcome measures of stroke severity and activities only, whereas functional
      improvement has been found to extend far beyond six months. Therefore, this study
      investigated relationships between infarct volume and a broad range of outcomes
      of stroke survivors at a long follow-up period. METHODS: Correlations between
      lesion volumes (determined by conventional MRI scans in the second week post
      stroke) and outcomes after one year of 75 first-ever ischemic stroke survivors
      were investigated. RESULTS: Moderate Spearman Rank correlation coefficients were
      found between lesion volume and motor impairment (Motricity Index (MI): -0.43, p
      < 0.01; Fugl Meyer Motor Assessment Scale (FM): -0.43; p < 0.01). Correlation
      coefficients with activities of daily living were moderate but low associated
      with Barthel Index (r(s) = 0.30; p < 0.01), modified Rankin Scale (r(s) = 0.39; p
      < 0.01) and Frenchay Activities Index (r(s) = -0.35; p < 0.01). Lesion volume had
      a significant but low association (r(s) = 0.27; p = 0.02) with patient's health
      status measured with Sickness Impact Profile 68 (SIP68)) and a moderate
      correlation with well-being assessed with Life Satisfaction Questionnaire (LSQ;
      r(s) = -0.45; p < 0.01). Found correlation coefficients were slightly stronger
      after correction for mixed (cortical/subcortical) and purely subcortical lesion
      location. CONCLUSIONS: It can be concluded that infarct volume moderately
      correlates with long-term motor impairment, functional outcome and quality of
      life of patients surviving stroke.

PMID- 16082083
TI  - Reinvestigation of Ge4Se9 based on single-crystal data.
AB  - Tetragermanium nonaselenide, Ge4Se9, adopts a two-dimensional layered structure.
      The layer is made up of infinite chains of corner-sharing GeSe4 tetrahedra and
      the chains are connected via the Ge2Se7 unit to form the two-dimensional layer.
      These layers are stacked to form the three-dimensional structure with a van der
      Waals gap. A previous structure report on Ge4Se9 based on powder diffraction data
      [Fjellvag, Kongshaug & Stolen (2001). J. Chem. Soc. Dalton Trans. pp. 1043-1045]
      is comparable with our results except for the absolute structure determination.

PMID- 16082084
TI  - [1,3-Bis(2-ethoxyphenyl)imidazolidin-2-ylidene]bromo(cycloocta-1,5
      diene)rhodium(I).
AB  - The title complex, [RhBr(C8H12)(C19H22N2O2)], has a distorted square-planar
      geometry. There are two molecules, A and B, in the asymmetric unit. The Rh-C bond
      distance between the N-heterocyclic ligand and the metal atom is 2.039 (2) A in
      molecule A and 2.042 (2) A in molecule B. The angle between the carbene
      heterocycle and the coordination plane is 87.56 (12) degrees in molecule A and
      87.03 (11) degrees in molecule B. It is shown that the average Rh-C(COD) (COD is
      cyclooctadiene) distance is linearly dependent on the Rh-C(imidazolidine)
      distance in this type of compound. This can be ascribed to the steric hindrance
      produced by the packing. The crystal structure contains intramolecular C-H...O
      and intermolecular C-H...Br interactions.

PMID- 16082085
TI  - Transition metal complexes with pyrazole-based ligands. XXII. Part XXI: Meszaros
      Szecsenyi, Leovac, Kovacs, Pokol & Jacimovic (2005). Di-mu-thiocyanato-bis[(3,5
      dimethyl-1H-pyrazole-1-carboxamidine-kappa2N,N')(thiocyanato-kappaN)copper(II)]
      and a redetermination of bis(3,5-dimethyl-1H-pyrazole-1-carboxamidine
      kappa2N,N')bis(nitrato-kappaO)copper(II).
AB  - The title Cu(II) complex, [Cu2(NCS)4(C6H10N4)2], represents the first crystal
      structure of a polynuclear transition metal complex with the 3,5-dimethyl-1H
      pyrazole-1-carboxamidine ligand (HL). It is compared with previously reported
      crystal structures of metal complexes with the same HL ligand. The molecule
      contains an eight-membered binuclear Cu2(NCS)2 ring, which is centrosymmetric and
      in a chair conformation. The Cu atom has a distorted square-pyramidal geometry
      with a very elongated Cu-S bond of 2.993 (2) A. The crystal structure
      redetermination of the bis(3,5-dimethyl-1H-pyrazole-1-carboxamidine
      kappa(2)N,N')bis(nitrato-kappaO)copper(II)complex, [Cu(NO3)2(C6H10N4)2], and
      analysis of its hydrogen bonds confirm the significance of the NO3 groups in the
      formation of a three-dimensional hydrogen-bonding network. Both complexes are
      centrosymmetric, the inversion centre being located at the mid-point of the
      Cu...Cu line in (I) and the Cu atom being located at the inversion centre in
      (II).

PMID- 16082086
TI  - Di-mu-chloro-1:2kappa2Cl;3:4kappa2Cl-hexachloro-1kappa3Cl,4kappa3Cl-tetra-mu
      dimethylglycine-2:3kappa8O:O'-tetracopper(II).
AB  - The title compound, [Cu(NO3)2(C6H10N4)2], crystallizes in the centrosymmetric
      space group P21/c with a unit cell containing two tetranuclear copper(II)
      complexes sited on crystallographic inversion centres. The coordination geometry
      around the central Cu atoms is square pyramidal, with four O atoms in the basal
      plane and a Cl atom in the apical position. The lateral CuCl4 groups are
      flattened tetrahedral. The bridging dimethylglycine molecules are present in the
      dipolar zwitterionic form. The tetranuclear copper complexes exist as isolated
      entities since only intramolecular hydrogen bonds are found.

PMID- 16082087
TI  - Dichloro{2-[2-(dimethylammonio)ethyliminomethyl]-4-nitrophenolato}zinc(II) in
      unsolvated and hemihydrate forms.
AB  - The two title complexes, [ZnCl2(C11H15N3O3)], (I), and
      [ZnCl2(C11H15N3O3)].0.5H2O, (II), are mononuclear zinc(II) compounds. In both
      structures, the Zn(II) atom is four-coordinated in a tetrahedral configuration by
      one imine N atom and one phenolate O atom of a Schiff base, and by two Cl atoms.
      The structure of each of the two zinc(II) complex molecules of (II) is similar to
      that of (I). In (I), the molecules are linked through intermolecular hydrogen
      bonds, forming a three-dimensional framework. In (II), the solvent water
      molecules are linked to the zinc(II) moieties through intermolecular O-H...O and
      O-H...Cl hydrogen bonds. The molecules in (II) are further linked via other
      intermolecular hydrogen bonds, forming a three-dimensional framework.

PMID- 16082088
TI  - A supramolecular zigzag chain of organometallic dipoles mediated by PF6- anions.
AB  - The title compound, (eta5-cyclopentadienyl)(4-nitrobenzonitrile
      kappaN)(trimethylphosphine-kappaP)(triphenylphosphite-kappaP)iron(II)
      hexafluorophosphate, [Fe(C5H5)(C7H4N2O2)(C18H15O3P)(C3H9P)]PF6, has been
      characterized by spectroscopic and X-ray diffraction in order to evaluate the
      tuning of the electron density at the metal centre and the extension of the pi
      delocalization on the molecule due to the presence of phosphite and phosphine co
      ligands. The compound crystallizes in the centrosymmetric space group P2(1)/c,
      which destroys the possibility of exhibiting any quadratic non-linear optical
      properties. The packing shows a supramolecular zigzag chain of antiparallel
      cations connected via the PF6- anions through C-H...F(delta-) interactions, with
      H...F distances ranging from 2.39 to 2.67 A. Each zigzag chain is composed of
      isomeric organometallic fragments containing either R or S molecules. These
      chains are connected through weak intermolecular C-H...C interactions, forming a
      two-dimensional plane parallel to (101).

PMID- 16082089
TI  - catena-Poly[[cyclo-tetra-mu-chlorotetracopper(I)]-bis{mu-3-[(2-morpholino-4-oxo
      4,5-dihydro-1,3-thiazol-5-ylidene)methylphenoxy]propene}
      2kappaN,1'eta2;1eta2,2'kappaN].
AB  - Crystals of a new copper(I) complex of composition [Cu4Cl4(C17H18N2O3S)2]n have
      been obtained by alternating-current electrochemical synthesis. In the crystal
      structure, the Cu and Cl atoms form a chair-like Cu4Cl4 cyclic fragment. The
      organic ligand acts as a bridge, being connected via the C=C bond of the allyl
      group to a Cu atom from one inorganic cycle and via the N atom of the thiazole
      ring to a Cu atom of another copper-chloride fragment. The geometry of the pi
      center indicates that the Cu-(C=C) interaction is moderately effective.

PMID- 16082090
TI  - Twisted [(R(3)P)PdX] groups above dicarbaborane ligands: 4-dimethylsulfido-3-iodo
      3-triphenylphosphine-closo-3-pallada-1,2-dicarbadodecaborane and 3
      dimethylphenylphosphine-3-chloro-4-dimethylsulfido-closo-3-pallada-1,2
      dicarbadodecaborane.
AB  - The structural analyses of [3-(PPh3)-3-I-4-(SMe2)-closo-3,1,2-PdC2B9H10] or
      [Pd(C4H16B9S)I(C18H15P)], (I), and [3-(PPhMe2)-3-Cl-4-(SMe2)-closo-3,1,2
      PdC2B9H10] or [Pd(C4H16B9S)Cl(C8H11P)], (II), show that in comparison with [3
      (PR3)2-closo-3,1,2-PdC2B9H11] the presence of the 4-SMe2 group causes the
      [PdX(PR3)] unit (X = halogen) to twist about an axis passing through the Pd atom
      and the directly opposite B atom of the carbaborane ligand. The halogen atoms are
      located almost directly above a C atom in the C2B3 face, and the conformations of
      the [PdX(PR3)] units above the C2B3 faces are not those predicted from molecular
      orbital calculations of the closo-3,1,2-PdC2B9 system. The fact that the
      variation from the predicted conformation is greater in the case of (I) than in
      (II) may be ascribed to the greater steric interactions induced by the I atom in
      (I) compared with the Cl atom in (II).

PMID- 16082091
TI  - A novel thiocyanate-bridged dinuclear cadmium(II) complex: di-mu-thiocyanato
      bis((methanol){4-nitro-2-[2
      (dimethylamino)ethyliminomethyl]phenolato}cadmium(II)).
AB  - The title complex, [Cd2(C11H14N3O3)2(NCS)2(CH4O)2], is an interesting thiocyanate
      bridged dinuclear cadmium(II) compound. It is located on a crystallographic
      inversion center. The CdII atom is six-coordinated in an octahedral configuration
      by one O and two N atoms of one Schiff base ligand and by the terminal N atom of
      a bridging thiocyanate ligand, defining the basal plane, and by the terminal S
      atom of another bridging thiocyanate ligand and by the O atom of a coordinated
      methanol molecule, occupying the axial positions. The molecules are linked
      through intermolecular O-HO hydrogen bonds, forming chains running along the b
      axis.

PMID- 16082092
TI  - trans-mu-Oxamido-N,N'-diethanoato-bis[diaquacopper(II)] dihydrate.
AB  - The title complex, trans-(mu-2,2'-[(1,2-dioxoethane-1,2
      diyl)diimino]diethanoato(4-))bis[diaquacopper(II)] dihydrate,
      [Cu2(C6H4N2O6)(H2O)4] x 2H2O, with a three-dimensional framework, displays a
      square-pyramidal coordination geometry. The structure consists of a neutral
      centrosymmetric binuclear unit in which the oxamide ligand has a trans geometry,
      is fully deprotonated and acts in a bis-tridentate fashion.

PMID- 16082093
TI  - 2-(2-Pyridyl)pyridinium perchlorate, redetermined at 120 K: complex hydrogen
      bonded sheets.
AB  - In the title compound, C10H9N2+.ClO4-, the ions are linked into complex sheets by
      the combination of one N-H...O and four independent C-H...O hydrogen bonds.

PMID- 16082094
TI  - 5-Phenyl-1,3,4-thiadiazol-2-yl 2,3,4,6-tetra-O-acetyl-1-thio-beta-D
      glucopyranoside.
AB  - The structure of the title compound, C22H24N2O9S2, is described. This compound
      consists of a sugar ring and a heterocyclic base linked unusually by an S atom.
      The sugar is in a 4C1 chair conformation and forms dihedral angles of 49.54 (4)
      and 33.42 (5)degrees with the thiadiazole and phenyl rings, respectively. The S
      atom occupies an equatorial position of the sugar ring and lies 1.807 (2) A out
      of the corresponding mean plane.

PMID- 16082095
TI  - Supramolecular structures of four (Z)-5-arylmethylene-2-thioxothiazolidin-4-ones:
      hydrogen-bonded dimers, chains of rings and sheets.
AB  - In each of the four title compounds, namely (Z)-5-benzylidene-2-thioxothiazolidin
      4-one, C10H7NOS2, (I), which crystallizes with Z' = 2 in space group P2(1)/n, (Z)
      5-(4-methylbenzylidene)-2-thioxothiazolidin-4-one, C11H9NOS2, (II), (Z)-2-thioxo
      5-[4-(trifluoromethyl)benzylidene]thiazolidin-4-one, C11H6F3NOS2, (III), and (Z)
      5-(4-methoxybenzylidene)-2-thioxothiazolidin-4-one, C11H9NO2S2, (IV), there is a
      very wide C-C-C angle (ca 130 degrees ) at the methine C atom linking the two
      rings. Pairs of N-H...O hydrogen bonds link the two independent molecules in (I)
      into a cyclic dimeric unit, and these units are further linked into complex
      sheets by three independent C-H...pi(arene) hydrogen bonds. The molecules of (II)
      are linked by paired N-H...O hydrogen bonds into centrosymmetric R(2)(2)(8)
      dimers; the molecules of (III) and (IV) are linked into chains of rings, which
      are constructed from a combination of N-H...S and C-H...O hydrogen bonds in
      (III), and from a combination of N-H...O and C-H...S hydrogen bonds in (IV).

PMID- 16082096
TI  - Effect of substitution on the dimensionality of supramolecular aggregation in
      dihydrobenzopyrazoloquinolines.
AB  - Molecules of 8-methyl-10-phenyl-6,10-dihydro-5H-benzo[h]pyrazolo[3,4-b]quinoline,
      C21H17N3, (I), are linked into cyclic centrosymmetric dimers by means of paired C
      H...N hydrogen bonds. In each of 8-methyl-7,10-diphenyl-6,10-dihydro-5H
      benzo[h]pyrazolo[3,4-b]quinoline, C27H21N3, (II), and 8-methyl-7-(4-methylphenyl)
      10-phenyl-6,10-dihydro-5H-benzo[h]pyrazolo[3,4-b]quinoline, C28H23N3, (III), the
      molecules are linked by C-H...pi(arene) hydrogen bonds into sheets, although the
      detailed construction of the sheets is entirely different in (II) and (III). The
      molecules of 7-(4-methoxyphenyl)-8-methyl-10-phenyl-6,10-dihydro-5H
      benzo[h]pyrazolo[3,4-b]quinoline, C28H23N3O, (IV), are linked into a complex
      three-dimensional framework structure by a combination of C-H...N, C-H...O and
      three independent C-H...pi(arene) hydrogen bonds.

PMID- 16082097
TI  - Two isomeric 10-methyl-8-phenyl-11-pyridyl-6,8-dihydro-5H-benzo[f]pyrazolo[3,4
      b]quinolines: cyclic hydrogen-bonded tetramers versus isolated molecules.
AB  - The molecules of 10-methyl-8-phenyl-11-(3-pyridyl)-6,8-dihydro-5H
      benzo[f]pyrazolo[3,4-b]quinoline, C26H20N4, (I), are linked by a single C-H...N
      hydrogen bond into cyclic R(4)(4)(12) tetramers generated by a -4 axis. In
      isomeric 10-methyl-8-phenyl-11-(4-pyridyl)-6,8-dihydro-5H-benzo[f]pyrazolo[3,4
      b]quinoline, (II), which crystallizes with Z' = 2 in space group P2(1)2(1)2, the
      two independent molecules are nearly enantiomeric but there are no direction
      specific interactions between them.

PMID- 16082098
TI  - Glyoxal 4-nitrophenylhydrazone: triple helices linked into a three-dimensional
      channel structure.
AB  - The molecules of the title compound, C8H7N3O3, which are nearly planar, are
      linked by an N-H...O hydrogen bond into helical chains, three of which are
      required to define the structure completely. These triply intertwined helices are
      linked by a C-H...O hydrogen bond into a three-dimensional framework enclosing
      two distinct types of channel, with average cross-sectional areas of 15.0 and 8.2
      A2.

PMID- 16082099
TI  - 3-(Triphenylphosphoranylidene)pentane-2,4-dione and diethyl 2
      (triphenylphosphoranylidene)malonate.
AB  - The title ylides, 3-(triphenylphosphoranylidene)pentane-2,4-dione, C23H21O2P,
      (I), and diethyl 2-(triphenylphosphoranylidene)malonate, C25H25O4P, (II), differ
      in the conformations adopted by their extended ylide moieties. In (I), one
      carbonyl O atom is syn and the other is anti with respect to the P atom, the
      ylide group is nearly planar, with a maximum P-C-(C=O) angle of 18.2 (2)degrees,
      and the P-C, C-C and C=O bond lengths are consistent with electronic
      delocalization involving the O atoms. In (II), both carbonyl O atoms are anti and
      the ester groups are twisted out of the plane of the near trigonal ylide C atom,
      reducing delocalization, the largest P-C-(C=O) angle being 30.2 (2)degrees.

PMID- 16082100
TI  - An oxonium hydrogen sulfate of 3a,6a-diphenylglycoluril.
AB  - In the title compound, (5-oxo-3a,6a-diphenylperhydroimidazo[4,5-d]imidazol-2
      ylidene)oxonium hydrogen sulfate, C16H15N4O2+ x HSO4-, the asymmetric unit
      contains a hydrogen sulfate anion and a 3a,6a-diphenylglycoluril oxonium cation.
      The hydrogen sulfate anion is joined to the oxonium cation via a strong O-H...O
      hydrogen bond (H...O = 1.69 A). The crystal packing is mainly dominated by
      interactions involving the hydrogen sulfate anion. The diphenylglycoluril oxonium
      cations also self-assemble through N-H...O hydrogen bonds, forming molecular
      chains along the [001] vector. Four intramolecular C-H...N hydrogen bonds are
      observed, having an S(5) motif.

PMID- 16082101
TI  - (E,E,E)-1,3,5-Tris[4-(acetylsulfanyl)styryl]benzene toluene hemisolvate.
AB  - The first crystal structure of a three-terminal sulfur end-capped
      oligophenylenevinylene, C36H30O3S3 x 0.5C7H8, has been determined at 122 (1) K.
      The molecular threefold symmetry is not utilized in the crystal structure. It is
      confirmed that the double bonds have been fully transformed into a trans
      configuration by iodine treatment.

PMID- 16082102
TI  - DL-Proline.
AB  - In the structure of DL-proline, C5H9NO2, the molecules are connected via
      classical intermolecular N-H...O hydrogen bonds involving the amine and carboxyl
      groups [N...O = 2.7129 (15) and 2.8392 (16) A], and form chains along the b-axis
      direction and parallel to (-101). The chains are linked into sheets via weak non
      classical hydrogen bonds. The conformation of the molecule and its packing are
      notably different from the monohydrated DL-proline form.

PMID- 16082103
TI  - 1-(4-Chlorophenyl)-2-methyl-4-nitro-5-(1-piperidyl)-1H-imidazole.
AB  - The only specific interactions that influence the crystal packing of the title
      compound, C15H17ClN4O2, are weak C-H...N and C-H...Cl hydrogen bonds, even though
      there is a possibility of, for example, pi-pi stacking or halogen bonding. The
      dihedral angle between the mean planes of the imidazole and benzene rings is
      59.82 (5) degrees . The length of the C-N bond connecting the imidazole and
      piperidine fragments is correlated with the degree of pyramidalization of the
      piperidine N atom.

PMID- 16082104
TI  - 2,2'-Dimethyl-4,5'-dinitro-1H,3'H-1,4'-biimidazole monohydrate.
AB  - The two almost perfectly planar imidazole rings in the title compound, C8H8N6O4 x
      H2O, make a dihedral angle of 63.01 (10) degrees . The water molecule acts as a
      double donor and double acceptor of strong and linear hydrogen bonds, including
      an exceptionally short C-H...O bond. These bonds create a tight three-dimensional
      structure and are probably responsible for the relatively high melting point of
      the compound.

PMID- 16082105
TI  - N-Methyl-N-(2-nitrophenyl)nitramine and N-methyl-N-(3-nitrophenyl)nitramine.
AB  - The structures of the two title isomeric compounds (systematic names: N-methyl
      N,2-dinitroaniline and N-methyl-N,3-dinitroaniline, both C7H7N3O4) are slightly
      different because they exhibit different steric hindrances and hydrogen-bonding
      environments. The aromatic rings are planar. The -N(Me)NO2 and -NO2 groups are
      not coplanar with the rings. Comparison of the geometric parameters of the ortho,
      meta and para isomers together with those of N-methyl-N-phenylnitramine suggests
      that the position of the nitro group has a strong influence on the aromatic ring
      distortion. The crystal packing is stabilized by weak C-H...O hydrogen bonds to
      the nitramine group.

PMID- 16082106
TI  - A non-natural dinucleotide containing an isomeric L-related deoxynucleoside:
      dinucleotide inhibitors of anti-HIV integrase activity.
AB  - The first X-ray crystal structure of a non-natural dinucleotide, 5'-O-phosphoryl
      1'-deoxy-2'-isoadenylyl-(3' --> 5')-cytidine 6.5-hydrate (pIsodApC),
      C19H26N8O13P2 x 6.5H2O, belonging to a family of dinucleotides that contain an
      isomeric nucleoside component, is described. A complex system of hydrogen bonds
      between water molecules and various sites on the dinucleotide was found. All H
      atoms were located from electron-density difference maps, which allowed
      identification of protonation sites. Compounds of this family have been found to
      bind at the active site of HIV integrase and to be inhibitors of this key viral
      enzyme. These dinucleotides are completely resistant to cleavage by exonucleases;
      an abnormal dihedral angle twist in an internucleotide phosphate bond revealed in
      the X-ray crystal structure may be contributing to this unusual stability towards
      nucleases.

PMID- 16082107
TI  - 1,5-Diphenyl-4,8-bis(3-phenylpyrazol-1-yl)pyrazabole.
AB  - The six-membered B2H4 ring of the title compound, C36H30B2N8, adopts a slightly
      distorted boat conformation, with the terminal B substituents in a trans
      orientation. One 3-phenylpyrazolyl group is in an equatorial position, whereas
      the second is in an axial position with respect to the plane defined by the B
      atoms.

PMID- 16082108
TI  - Dimorphism in 3'-aminocyclohexanespiro-5'-hydantoin.
AB  - The title compound [systematic name: 1'-aminocyclohexanespiro-4'-imidazole
      2',5'(3'H,4'H)-dione], C8H13N3O2, has been synthesized and was found to
      crystallize in two different structures, both monoclinic and both with the same
      P2(1)/c space group. In the first structure, there are two molecules in the
      asymmetric unit, one of which uses all of its hydrogen-bond donors and acceptors
      and forms undulating layers, while the other forms chains propagating
      perpendicular to the layers. In the second structure, there is only one
      independent molecule and the packing is based on a chain structure mediated by
      hydrogen bonding between the hydantoin moieties and further grouped into
      hydrophilic layers separated by layers of the hydrophobic cyclohexyl groups.

PMID- 16082109
TI  - (E)-2-Methyl-3-(2-methyl-2-nitrovinyl)-1H-indole and (E)-3-(2-methyl-2
      nitrovinyl)-2-phenyl-1H-indole.
AB  - In the title compounds, C12H12N2O2, (I), and C17H14N2O2, (II), respectively, the
      indole rings are planar and the vinyl groups lie out of the indole planes, making
      dihedral angles of 33.48 (5) and 41.31 (8) degrees , respectively. In (II), the
      dihedral angle between the phenyl and indole ring planes is 32.06 (6) degrees .
      In both molecules, the double bond connecting the methylnitrovinyl group and the
      indole nucleus adopts an E configuration. Notwithstanding the differences in
      space group [C2/c for (I) and P2(1)2(1)2(1) for (II)], the mode of packing of
      compounds (I) and (II) is determined by similar intermolecular N-H...O hydrogen
      bonding interactions, forming chains that run parallel to [101] in (I) and [001]
      in (II).

PMID- 16082110
TI  - Changes in orexin-A and neuropeptide y expression in the hypothalamus of obese
      and lean Zucker Diabetic Fatty rats.
AB  - This study was carried out to investigate the changes of orexin-A (OXA) and
      neuropeptide Y (NPY) expression in the hypothalamus of the obese and lean Zucker
      Diabetic Fatty (ZDF) rats which have a missense mutation in the leptin receptor
      gene. The mean body weights (MBW) between the obese and lean ZDF rats were
      significantly different at 28 and 70 postnatal days. However, at 14 postnatal
      day, there was no significant difference in the MBW between the obese and lean
      ZDF rats in both male and female. The OXA immunoreactivities were not
      significantly different between the obese and lean ZDF rats in both sexes at 14,
      28, and 70 postnatal days, respectively. The NPY immunoreactivity was higher in
      the obese than in the lean ZDF rats in both male and female at 28 and 70
      postnatal days, whereas there was no significant difference between the obese and
      lean ZDF rats at 14 postnatal day. These results indicate that both OXA and NPY
      might halt their roles for food intake in the obese phenotype of the male and
      female ZDF rats in the preweaning period of 14 postnatal day, whereas NPY might
      play a main role in the obesity of these rats in the weaning period of 28 and 70
      postnatal days.

PMID- 16082111
TI  - Molecular epidemiological analysis of bat rabies viruses in Brazil.
AB  - A molecular epidemiological analysis was performed in 19 rabies viruses (RVs)
      isolated from haematophagous, frugivorous and insectivorous bats, in Sao Paulo,
      Brazil. The authors carried out RT-PCR for amplification of the RV nucleoprotein
      (N) gene, and determined 1,335 nucleotide sequences of N gene by direct
      sequencing method. Phylogenetic analysis, which was based on the N gene of
      Brazilian RV isolates identified presently and previously, revealed that RVs
      isolated from bats were genetically divided into four lineages had a tendency to
      depend on the host bat species. The first lineage consisted mainly of
      haematophagous bat (Desmodus rotundus) isolates, including frugivorous bat
      (Artibeus spp.) isolates. Other three lineages consisted of insectivorous bat
      isolates; mainly Eptesicus spp., Molossus spp. and Nyctinomops spp. isolates,
      respectively. These results indicate a possibility of that there are bat species
      specific RV variants in Brazil.

PMID- 16082112
TI  - Preference for safflower oil in rats exposed to a cold environment under free
      feeding conditions.
AB  - There are several benefits to a high-fat diet for animals exposed to cold,
      including improved tolerance to severe cold conditions and increased survival
      rates in cold environments. It is therefore of interest to examine whether
      animals exposed to cold will selectively consume lipids. We examined the intake
      of safflower oil (SO) by rats exposed to cold (4 +/- 2 degrees C) under a feeding
      condition in which the rats were given free access to SO. Rats exposed to cold
      consumed more SO than those housed at 25 +/- 2 degrees C. This finding suggests
      that rats prefer SO in a cold environment. There was no significant difference in
      the ratio of calories of SO ingested to that of matter (standard laboratory chow
      plus SO) ingested between rats exposed to cold and those at 25 +/- 2 degrees C.
      The high SO intake also affected cold tolerance and metabolite kinetics in the
      rats. Factors that affected the SO intake of rats exposed to cold are also
      discussed.

PMID- 16082113
TI  - Effects of various selective phosphodiesterase inhibitors on carbachol-induced
      contraction and cyclic nucleotide contents in the guinea pig gall bladder.
AB  - The effects of various selective phosphodiesterase (PDE) inhibitors on muscle
      contractility and cyclic nucleotide contents in the guinea pig gall bladder were
      investigated. Various selective PDE inhibitors, vinpocetine (type 1), erythro-9
      (2-hydroxy-3-nonyl)adenine (EHNA, type 2), milrinone (type 3), Ro20-1724 (type
      4), and zaprinast (type 5), inhibited CCh-induced contractions in a concentration
      dependent manner. The rank order of potency for the gall bladder was Ro20-1724 >
      vinpocetine > EHNA > milrinone > zaprinast, which was different from that of the
      trachea, taenia coli, and aorta. In the presence of CCh (0.3 muM), vinpocetine,
      milrinone, and Ro20-1724 each increased cAMP content, but not cGMP. By contrast,
      zaprinast increased cGMP content, but not cAMP, and EHNA increased both cAMP and
      cGMP contents. These results suggest that vinpocetine-, milrinone-, and Ro20-1724
      induced relaxation was correlated with cAMP, zaprinast-induced relaxation was
      correlated with cGMP, and that EHNA-induced relaxation was correlated with cAMP
      and cGMP in the guinea pig gall bladder. In conclusion, the effect of PDE
      inhibitors in the guinea pig gall bladder was different from those in smooth
      muscles, such as the trachea, taenia coli, and aorta.

PMID- 16082114
TI  - Small molecule lactoferrin with an inflammatory effect but no apparent
      antibacterial activity in mastitic mammary gland secretion.
AB  - We have identified various lactoferrin (Lf) molecules in mastitic mammary gland
      secretions (MGSs), and these Lf molecules were examined for their physiological
      function in MG. These Lf molecules were isolated by Con A affinity
      chromatography, and then analyzed by various electrophoresis methods and N
      terminal amino acid sequencing. The low Con A affinity Lf was found to have low
      molecular peptides as compared with the 86 kDa of the high Con A affinity Lf,
      which is usually detected in healthy MGSs. The N-terminal amino acid sequence of
      each of the small molecular Lfs were confirmed as fragments of 86 kDa Lf. This
      low Con A affinity Lf stimulated spleen adherent cells to produce more O(2)(-)
      than 86 kDa Lf. Furthermore, the low Con A affinity Lf showed low antibacterial
      activity against E. coli and S. aureus, and had decreased iron-binding capacity
      in comparison with 86 kDa Lf. Moreover, the 86 kDa Lf could stimulate bovine T
      cells or macrophages to produce IFN-gamma, IL-4, IL-6, and IL-1alpha. However low
      Con A affinity Lf induced the production of TNFalpha, but not physiological T
      cell or macrophage cytokines. It was also found that when the healthy MGs of dry
      cows were injected with the low Con A affinity Lf, there was an increase in
      polymorphonuclear cells together with TNFalpha, MCP-1, and IL-8 production. These
      results suggested that low Con A affinity Lf in mastitic MGSs differed from 86
      kDa Lf in physiological characteristics, and, that it induced an inflammatory
      reaction in MGs.

PMID- 16082115
TI  - Usefulness of hemilaminectomy for cervical intervertebral disk disease in small
      dogs.
AB  - Hemilaminectomy was performed to treat cervical disc disease in 18 small dogs.
      Cervical spinal cord compression was characterized by ventral and/or lateral
      compression on myelograms. The duration of follow-up examinations ranged from 2
      to 72 months. The optimal response time after surgery ranged from 2 days to 3
      months. The outcome was determined to be excellent if clinical signs resolved and
      the dog had completely improved. The outcome was determined to be good if the dog
      improved, but was not clinically normal or if the degree of the owner's
      satisfaction was insufficient. Fourteen dogs achieved complete neurologic
      recovery without complications. One dog was initially neurologically worse after
      surgery, but ultimately improved to normal neurologic status. These outcomes were
      judged to be excellent. In the remaining 3 dogs, 2 dogs had relapse of neck pain
      and one dog remained mildly ataxic. These outcomes were judged to be good. These
      results suggest that hemilaminectomy is an effective option for surgical
      treatment of spinal cord compression secondary to cervical disc disease in small
      dogs.

PMID- 16082116
TI  - Unilateral basement membrane zone alteration of the regenerated laminar region in
      equine chronic laminitis.
AB  - Between the laminar epidermis and the laminar dermis of laminar region (LR) in
      equine foot, it can be observed the basement membrane zone (BMZ), which is
      composed of a basement membrane and its accompaniments like the hemidesmosome and
      anchoring fibril. Alteration in the BMZ in equine laminitis is possibly related
      with not only development but also recovery outcome and recurrence of this
      disease. However, there is little known about the structure of the BMZ during the
      recovery phase of this disease. To assess the condition of the BMZ of LR affected
      by chronic laminitis, the tissue was examined in three cases at two weeks, four
      weeks and three months after the onset of laminitis, using pathological,
      immunohistochemical and electron microscopic techniques. Histologically in all
      laminitis cases, there was a regenerated laminar epidermis with proliferating
      keratinocytes between the Stratum medium and the dermis, but it included the
      undeveloped secondary epidermal laminae (ud-SELs) structure in one side of the
      primary epidermal laminae, especially in the part of the deep area of LR.
      Immunohistochemical results were positive for the anti-type IV collagen, anti
      type VII collagen and anti-laminin 5 antibodies in the most BMZs. However,
      partial BMZs adjacent to the ud-SELs were negative for the anti-type VII collagen
      and anti-laminin 5 antibodies. Ultrastructurally, in the BMZ of the ud-SEL, the
      lamina densa and the lamina lucida were present. In contrast, the anchoring
      fibrils and the hemidesmosomes were either absent, or present at lower than
      normal levels. In conclusion, the present study indicated that the part of
      regenerated LR in chronic laminitis was not able to fully restore to construct
      the BMZ for a long time, especially in the unilateral side of laminar epidermis.
      It might be related with recurrence of this disease.

PMID- 16082117
TI  - An outbreak of systemic granulomatous disease in cows with high milk yields.
AB  - Seven of 92 lactating Holstein cows on a dairy farm developed urticaria with
      alopecia and decreased milk production, and three of the seven died over the
      course of 7 to 18 days. Pathologic examination of the three cows, including the
      two dead and one euthanized cow, revealed that the skin, liver, spleen, kidneys,
      heart, salivary glands, pancreas, adrenal glands, mammary glands, lymph nodes,
      and trigeminal ganglia had lymphocytic to lymphogranulomatous inflammation.
      Inflammation predominated by lymphocytic infiltration was prominent in the heart,
      pancreas, mammary glands, adrenal gland, and trigeminal ganglia. Severe
      granulomatous inflammation with multinucleated giant cells was present in the
      spleen and kidneys. These lesions and their distributions were most similar to
      those seen in suspected cases of citrus pulp toxicosis and hairy vetch toxicosis.
      The outbreak of this disease resolved with the elimination of Citrus pulp from
      the feed. Immunohistochemical detection of lymphocytes and macrophage markers
      confirmed dramatic hyperplasia of CD3-positive T lymphocytes in these lesions.
      This strongly suggested that a type 4 hypersensitivity reaction played a role in
      the development of the lesions.

PMID- 16082118
TI  - Differential expression of neurofilament 200-like immunoreactivity in the main
      olfactory and vomeronasal systems of the Japanese newt, Cynops pyrrhogaster.
AB  - Expression of neurofilament 200 (NF200)-like immunoreactivity was examined in the
      main olfactory system and the vomeronasal system of the Japanese newt, Cynops
      pyrrhogaster, using anti-porcine NF200 monoclonal antibody (clone N52) to
      investigate the differences in phenotypical characteristics between these
      systems. The entire nasal cavity was a flattened single chamber consisting of the
      main nasal chamber (MNC) and the lateral nasal sinus (LNS) communicating with
      each other. The olfactory epithelium (OE) was present in the MNC, and the
      vomeronasal epithelium (VNE) was in the LNS. The OE possessed only a small number
      of NF200-like immunoreactive receptor neurons. The olfactory nerve and the
      olfactory nerve layer of the main olfactory bulb also contained a small number of
      NF200-like immunoreactive axons. In contrast, the VNE possessed many NF200-like
      immunoreactive receptor neurons. The vomeronasal nerve and the vomeronasal nerve
      layer of the accessory olfactory bulb contained many NF200-like immunoreactive
      axons. These findings in the Japanese newt indicate that NF200-like
      immunoreactive receptor neurons constitute a major subpopulation in the VNE and a
      minor subpopulation in the OE. In addition, NF200-like immunoreactivity seems to
      be a useful marker to distinguish the vomeronasal system from the other nervous
      systems including the main olfactory system in the Japanese newt. The
      localization of a few NF200-like immunoreactive receptor neurons in the OE might
      indicate that pheromone-sensitive receptor neurons are intermingled in the OE of
      the Japanese newt.

PMID- 16082119
TI  - A novel method for estimating the adaptive ability of guide dogs using salivary
      sIgA.
AB  - Salivary secretory immunoglobulin A (sIgA) concentrations of prospective guide
      dogs for the blind were determined to clarify whether salivary sIgA is useful in
      evaluating the potential suitability of guide dogs for the blind. Saliva was
      collected from 73 prospective guide dogs in the kennel on day 1 (the day of
      separation from volunteer puppy-raisers), 2, 3, 7 and 14 during the estimation
      period (at about 1 year old). We selected particularly suitable dogs (superior
      dogs) and unsuitable dogs (inferior dogs) on the basis of the trainers'
      estimation. All dogs were divided into two groups, those were acceptable dogs
      would become the guide dogs and rejected dogs could not become guide dogs. The
      sIgA concentrations in superior dogs gradually increased from day 1 to 14 and
      those in inferior dogs remained at low levels. Moreover, the sIgA concentrations
      on day 14 in the acceptable dogs were significantly higher than those in rejected
      dogs. The cut-off point of sIgA concentrations on day 14 using an ROC curve was
      90 EU/ml, and the specificity of the estimation at this point (70.4%) was higher
      than that of trainers' estimation (50%). Moreover, parallel testing using both
      trainers' estimation and sIgA estimation, showed that specificity was further
      improved (79.5%). The present study showed that sIgA concentration was extremely
      useful in estimating the adaptive ability for guide dogs for the blind.

PMID- 16082120
TI  - Factor XI mutation in a Holstein cow with repeat breeding in Japan.
AB  - Factor XI deficiency is an autosomal recessive coagulopathy in Holstein cattle.
      Affected cows have a tendency to show repeat breeding. Forty repeat breeding
      Holstein Friesian cows were selected and tested for the Factor XI mutation.
      Genomic DNA was isolated from the blood of the cows (n=40). Exon 12 of the Factor
      XI gene of the cows was amplified by PCR. One repeat breeding cow was
      heterozygous to the Factor XI mutation as indicated by the presence of two DNA
      fragments of 320 bp and 244 bp. The insertion of the 76 bp in the heterozygous
      cow was confirmed by DNA sequencing. The heterozygous cow was in her fourth
      lactation. She gave birth to male twins at the last calving. She was inseminated
      artificially four times after the last calving. Factor XI deficiency in cattle
      has been reported in different countries. However, no case was reported in Japan.
      This might be the first to report Factor XI mutation in Holstein cattle in Japan.

PMID- 16082121
TI  - Prevalence of Giardia intestinalis infection in dogs of breeding kennels in
      Japan.
AB  - Giardia intestinalis antigen in fecal samples was examined in 361 dogs of 14
      breeding kennels located at various areas in Japan, using a commercial enzyme
      linked immunosorbent assay (ELISA) kit. G. intestinalis antigen was detected in
      37.4% of the fecal specimens. All of the 14 breeding kennels were positive for G.
      intestinalis antigen with the range from 6.7 to 59.3%. The prevalence in puppies
      (54.5%) was significantly (p < 0.01) higher than that in adults (30.9%). There
      was no difference in prevalence between males and females, and between the
      puppies from the mother dogs positive and negative for Giardia antigen. In
      conclusion, G. intestinalis widely invaded the breeding kennels in Japan.

PMID- 16082122
TI  - Effectiveness of intraoperative somatosensory evoked potential monitoring during
      cervical spinal operations on animals with spinal cord dysfunction.
AB  - We conducted somatosensory evoked potential (SEP) monitoring on 3 dogs with
      cervical spinal cord dysfunction caused by various diseases throughout operative
      procedures to examine whether the intraoperative SEP monitoring was effective for
      prediction of spinal cord conductive function. The SEP was recorded on the scalp
      via stimulation of the ulnar nerve. Stable SEP was recorded in all animals
      examined. Its amplitude was decreased by surgical manipulations of the regio
      vertebralis, but the amplitude gradually recovered once the manipulations were
      halted. The latency showed small variation throughout the operations. This
      evidence suggests that intraoperative SEP monitoring may provide continuous and
      instantaneous information regarding the functional integrity of the central
      nervous system.

PMID- 16082123
TI  - Trochleoplasty in lateral patellar luxation in two calves.
AB  - Two Holstein Friesian calves were referred to the Animal Medical Center of
      Chonbuk National University with severe lameness on the hind limb(s), flexed
      stifle joint and an inability to walk since birth. Based on the clinical history,
      clinical findings and radiography of the stifle joint, the cases were diagnosed
      as grade III lateral patellar luxation (LPL). Trochleoplasty along with medial
      retinacular reinforcement and lateral release were performed in both calves. The
      calves recovered 3 to 4 weeks after surgery. Trochleoplasty along with medial
      retinacular reinforcement and lateral release can be an effective technique for
      the treatment of LPL in calves.

PMID- 16082124
TI  - Usefulness of intraoperative ultrasonography for two dogs with spinal disease.
AB  - Intraoperative ultrasonography was performed during spinal surgery in two dogs.
      An extradural lesion was demonstrated by myelography in case 1, and an extradural
      tumor was found during surgery. Case 2 was diagnosed with a spinal subarachnoid
      cyst by myelography and magnetic resonance imaging. Ultrasonographically,
      pathologic conditions of the spinal canal or cord were adequately imaged during
      surgery in both cases. Intraoperative ultrasonography was a superior method that
      non-invasively revealed intradural and extradural conditions and thus constitutes
      a valuable diagnostic mean to ensure safe and precise spinal surgery.

PMID- 16082125
TI  - Antioxidative and antigenotoxic effects of Japanese horse chestnut (Aesculus
      turbinata) seeds.
AB  - Japanese horse chestnut seed extract (HCSE) dose-dependently inhibited the
      autooxidation of linoleic acid (IC(50): 0.2 mg/ml), and the inhibition was almost
      complete at a concentration of 1 mg/ml. The HCSE scavenged DPPH (1,1-diphenyl-2
      picrylhydrazyl) radicals and superoxide anions with EC(50)s of 0.65 and 0.21
      mg/ml, respectively. However, it had no effect on hydrogen peroxide. The HCSE
      inhibited the genotoxicities of furylfuramide, N-methyl-N-nitrosourea, methyl
      methanesulfonate, mitomycin C, 2-aminoanthracene and aflatoxin B1 at a
      concentration of 1 mg/ml or more. Total polyphenol content of the HCSE was 21
      mg/g (13 mg/g-seeds). These results indicate that the Japanese horse chestnut
      seed is an antioxidative and antimutagenic botanical resource.

PMID- 16082126
TI  - Nonsuppurative myocarditis caused by porcine circovirus type 2 in a weak-born
      piglet.
AB  - Reproductive failure associated with porcine circovirus type 2 (PCV2) was
      observed in a farm, and a weak-born 8-day-old piglet was examined pathologically.
      Focal to locally extensive lesions, including infiltration of macrophages and
      lymphocytes, fibrosis and degeneration of the myocardium were observed in the
      heart. PCV2 antigens and nucleic acids were detected in degenerated
      cardiomyocytes and macrophages infiltrating the heart by immunohistochemical
      staining and in situ hybridization. Depletion of lymphocytes with occasional
      infiltration of multinucleated giant cells was seen in the lymphoid organs and
      PCV2 antigens were demonstrated in histiocytic cells. Crystalline arrays of viral
      particles were observed in infiltrated macrophages in the heart and, rarely, in
      cardiomyocytes by electron microscopy. Although myocarditis is a common finding
      in aborted or stillborn piglets in reproductive failure due to PCV2, it was also
      observed in the 8-day-old piglet with PCV2 association.

PMID- 16082127
TI  - Clinical features and rapid plasma reagin antibody titers in spontaneous and
      experimental rabbit syphilis.
AB  - Rapid plasma reagin (RPR) titers were periodically examined during and after
      treatment in three rabbits clinically diagnosed with rabbit syphilis. RPR titers
      remained positive after clinical recovery and then gradually declined. Of the two
      rabbits inoculated experimentally, one showed clinical signs of the disease,
      while the other did not. RPR titers were also periodically evaluated before and
      after inoculation in these two rabbits. The trends in RPR titers reflected the
      course of infection, both in the spontaneous and in the experimental cases. An
      inapparent case and cases without clinical signs after clinical recovery showed
      low titers for long period of time. Useful information for interpretation of RPR
      titers measured clinically was obtained by this survey.

PMID- 16082128
TI  - Dynamic MR cholangiography after fatty meal loading: cystic contractility and
      dynamic evaluation of biliary stasis.
AB  - PURPOSE: Dynamic MR cholangiography was conducted on patients with cholelithiasis
      or choledocholithiasis who had consumed a fatty test meal (Molyork) and the
      cystic contractility and dynamics of biliary stasis was evaluated. SUBJECTS AND
      METHOD: The subjects were 25 with intracystic cholelithiasis, 10 with
      choledocholithiasis and 10 normal controls. For an imaging sequence, the rapid
      acquisition with relaxation enhancement (RARE) method was employed and imaging
      was conducted for 40 min (every 30 s following Molyork administration) without
      breath-holding. The gallbladder contraction ratio was computed and the
      contractile ratio for the common bile duct was calculated. To determine the bile
      flow to the duodenum, the high-intensity signal, indicating the flow from the
      lower common bile duct, and perfusion of the duodenum were observed in dynamic
      mode on the monitor with the naked eye and interpreted as positive bile flow. The
      frequency of this flow was visually monitored. RESULTS: The gallbladder
      contractile ratio was significantly reduced in patients with cholelithiasis or
      choledocholithiasis compared with the controls. In a comparison with the normal
      controls, no sequential changes were noted in the mean contractile ratio of the
      common bile duct of the patients with cholelithiasis or choledocholithiasis. The
      mean frequency of bile flow observed for each 40 min period was 13+/-2.4, 6+/
      2.2, and 4+/-1.3 times for the controls, those with intracystic cholelithiasis,
      and those with choledocholithiasis, respectively. Compared with the controls, the
      latter two patient groups showed evident reductions in the frequency of bile flow
      to the duodenum (p<0.001). CONCLUSION: Dynamic MRC combined with Molyork loading
      makes it possible to compute cystic contractile ratios and perform a dynamic
      examination of bile flow under non-invasive, near-physiological conditions.

PMID- 16082129
TI  - Efficacy of MR mammography (MRM) in providing preoperative locoregional
      information on breast cancer: correlation between MRM and histological findings.
AB  - RATIONALE AND OBJECTIVES: To assess the efficacy of MRM in providing preoperative
      locoregional information on patients with breast cancer. METHODS: MRI was
      performed on 62 female breast cancer patients. A 1.5T MR-system was used to
      acquire fat-suppressed T(1)WI, T(2)WI and dynamic-contrast-enhanced images with
      an SPGR pulse sequence. The extent of the cancer measured with MRM was confirmed
      histologically in all patients. RESULTS: The size obtained from MRM correlated
      well with the size obtained histologically, including intraductal spread of
      cancer (R: 0.853). As for shape, the round/oval type evident from MRM correlated
      more accurately (R: 0.934) than the ill-defined type associated with a linear
      and/or clumped enhanced area (R: 0.744). The difference between the size obtained
      from MRM and the size obtained histologically, including IDS, was less than 15 mm
      in the majority of patients (93.5%). CONCLUSIONS: MRM accurately reveals the
      extent of cancer, including IDS, and is effective at providing preoperative
      locoregional information for breast-conserving therapy for breast cancer.

PMID- 16082130
TI  - Moderately T2-weighted images obtained with the single-shot fast spin-echo
      technique: differentiating between malignant and benign urinary obstructions.
AB  - The purpose of this study was to determine whether a distinction could be made
      between benign and malignant urinary obstructions in moderately T(2)-weighted
      images obtained with the single-shot fast spin-echo technique. Forty-four lesions
      in 39 patients with urinary obstruction were evaluated with the single-shot fast
      spin-echo (SSFSE) technique with an effective TE of 90-100 ms and without fat
      saturation. Benign and malignant lesions were compared for the presence of
      ureteral wall thickening and a signal intensity relative to the proximal ureteral
      wall. Statistically significant differences were found between benign and
      malignant lesions in both morphologic change (P<0.0001) and signal intensity of
      the lesions at the obstruction position (P<0.0001). The combination of wall
      thickening and increased signal intensity as a predictor of malignant disease
      yielded a sensitivity of 88% and a specificity of 100%. Neither increased signal
      intensity nor wall thickening as a predictor of benign disease yielded a
      sensitivity of 89% and a specificity of 88%. The moderately T(2)-weighted SSFSE
      technique without fat saturation can accurately distinguish between benign and
      malignant urinary obstructions.

PMID- 16082131
TI  - Myths and truths in functional MRI: a basic guide for practitioners.
AB  - Since the first successful demonstration of primary visual cortex "activation" by
      Sokoloff in 1961, activation studies based on regional blood flow alteration
      became one of the gold standards for neuroscientific investigation. The rapid
      advancement of non-invasive imaging techniques provided an appropriate stage for
      the human application of this original method. Following the tremendous success
      of positron emission tomography (PET) utilizing O(15) labeled H(2)O (H(2)O(15)
      PET), the magnetic resonance imaging (MRI) version, which is now referred to as
      functional MRI (fMRI), was introduced. fMRI is the method created based on the
      empirical observation that MRI exhibits spontaneous signal alteration associated
      with blood flow changes. It is now believed that the principle of fMRI is
      identical to H(2)O(15)-PET, namely, that it is blood flow based in accordance
      with the well-known Munro-Kellie doctrine which predicts a decline in cerebral
      venous blood volume secondary to an increase in cerebral arterial blood volume.
      The method is inherently qualitative and does not provide quantitative
      information regarding flow alteration. With the growing use of fMRI, however,
      exponentially increasing well founded criticism questioning the validity of fMRI
      data has been raised. The majority of validation issues arise during the process
      of obtaining raw images, which eventually provides raw numerical data for post
      processing statistical analysis. This article provides a distillation of the
      essential knowledge necessary for the non-MR physicist fMRI investigator.

PMID- 16082132
TI  - Functional MRI in human motor control studies and clinical applications.
AB  - Functional magnetic resonance imaging (fMRI) has been a useful tool for the
      noninvasive mapping of brain function associated with various motor and cognitive
      tasks. Because fMRI is based on the blood oxygenation level dependent (BOLD)
      effect, it does not directly record neural activity. With the fMRI technique,
      distinguishing BOLD signals created by cortical projection neurons from those
      created by intracortical neurons appears to be difficult. Two major experimental
      designs are used in fMRI studies: block designs and event-related designs. Block
      designed fMRI presupposes the steady state of regional cerebral blood flow and
      has been applied to examinations of brain activation caused by tasks requiring
      sustained or repetitive movements. By contrast, the more recently developed event
      related fMRI with time resolution of a few seconds allows the mapping of brain
      activation associated with a single movement according to the transient aspects
      of the hemodynamic response. Increasing evidence suggests that multiple motor
      areas are engaged in a networked manner to execute various motor acts. In order
      to understand functional brain maps, it is important that one understands
      sequential and parallel organizations of anatomical connections between multiple
      motor areas. In fMRI studies of complex motor tasks, elementary parameters such
      as movement length, force, velocity, acceleration and frequency should be
      controlled, because inconsistency in those parameters may alter the extent and
      intensity of motor cortical activation, confounding interpretation of the
      findings obtained. In addition to initiation of movements, termination of
      movements plays an important role in the successful achievement of complex
      movements. Brain areas exclusively related to the termination of movements have
      been, for the first time, uncovered with an event-related fMRI technique. We
      propose the application of fMRI to the elucidation of the pathophysiology of
      movement disorders, particularly dystonia, which exhibits involuntary co
      contraction of agonist and antagonist muscles and manifests abnormal posture or
      slow repetition of movements.

PMID- 16082133
TI  - Evaluation of efficacy of an automated single-voxel proton MRS algorithm on a 3T
      system.
AB  - PURPOSE: To evaluate the efficacy of a fully automatic, single-voxel, proton MR
      spectroscopy algorithm on a 3.0T MR system. METHODS: The PROBE/SVQ algorithm (GE
      Medical Systems) was evaluated on a General Electric (GE) Signa LX-3T system. Ten
      normal volunteers (female, 21.1+/-2.0 years old) participated in the study. Nine
      representative regions of interest were examined, namely, right and left frontal
      white matter; right and left parietal white matter; right and left basal ganglia;
      right and left dentate nucleus; and pons. RESULTS: The mean coefficients of
      variation in all regions for the N-acetyl-aspartate to creatine ratio (NAA/Cr),
      choline to creatine ratio (Cho/Cr), and choline to N-acetyl-aspartate ratio
      (Cho/NAA) were 10.2+/-2.4%, 11.4+/-3.2% and 12.6+/-1.4%, respectively.
      CONCLUSION: A fully automated spectroscopic examination under clinical setting
      utilizing the PROBE/SVQ algorithm appears to be a reliable method, extending the
      window of routine clinical assessment of brain metabolism.

PMID- 16082134
TI  - Adenomyomatosis with marked subserosal fibrosis and lipomatosis of the
      gallbladder: mural stratification demonstrated with MR.
AB  - The authors reported a case of fundal-type adenomyomatosis in which mural
      stratification corresponding to histopathological findings was clearly
      demonstrated with MR imaging. Single-shot fast spin echo images for MR
      cholangiopancreatography clearly visualized Rokitansky-Aschoff sinuses (RAS),
      which are a diagnostic clue for this disease. However, mural stratification
      comprising RAS with muscular proliferation, massive fibrosis and subserosal fat
      deposition was more precisely demonstrated in T(2)-weighted images obtained with
      fast spin echo.

PMID- 16082135
TI  - A device for MR imaging of atherosclerosis plaque in carotid endarterectomy
      specimens ex vivo.

PMID- 16082136
TI  - Flow-weighted MRI of the lungs with the ECG-gated half-Fourier FSE technique:
      evaluation of the effect of the cardiac cycle.
AB  - We investigated temporal MR signal changes in the peripheral lung and proximal
      pulmonary vessels during the entire cardiac cycle in order to evaluate the
      characteristics of the diastolic-systolic subtraction method in the lung. In
      eight healthy volunteers free of lung diseases, changes in the MR signal during
      one breath-hold were investigated with the multiple ECG-triggered half-Fourier
      single-shot fast-spin echo (SS-FSE) technique. The signal intensity-time course
      curve in the lung showed that biphasic signals decreased 20% to 47% at systole
      and 5% to 33% at mid-diastole, measured against the maximum signals at late
      diastole. This signal decrease in the peripheral lung was correlated to that in
      the proximal pulmonary vessels during an entire cardiac cycle (r=0.667 to 1.000).
      The best visualization of the lung was obtained at late diastole, when the intra
      vascular flow in the lung was expected to be stagnant. Compared with the late
      diastolic SS-FSE images, the late diastolic-systolic subtracted SS-FSE images
      improved the signal-to-noise ratio in the lung as well as the signal-intensity
      ratio of the peripheral lung to surrounding tissues. Although the flow-induced
      signal dephasing in the lung was completely unavoidable and its amount was
      unpredictable even at late diastole, the diastolic-systolic subtracted SS-FSE
      images showed the relative differences in flow alteration during the cardiac
      cycle between the images at diastole and those at systole. The main
      characteristic of diastolic-systolic subtracted SS-FSE was the enhancement of
      visibility of cardiac-dependent signal changes in the lung due to the alteration
      in pulsatile flow.

PMID- 16082137
TI  - Increased signal intensity in the normal glenoid labrum in MR imaging: diagnostic
      pitfalls caused by the magic-angle effect.
AB  - PURPOSE: To determine the effect of the magic-angle effect on the MR signal in
      the posterosuperior portion of the glenoid labrum. METHODS: MR imaging of 15
      arthroscopically evaluated shoulders, five with posterosuperior labrum injury and
      ten intact, was retrospectively reviewed. In the first part of the study, the
      signal intensity of the posterosuperior labrum on gradient-recalled echo (GRE)
      T2*-weighted axial images was correlated with the arthroscopy findings. The
      second part of the study was designed to illustrate the orientation-dependent
      signal that occurs in the posterosuperior labrum of three asymptomatic volunteers
      when imaged in the conventional supine position and in a position similar to
      Trendelenburg's. Another three volunteers were examined with GRE T2*-weighted
      axial images to assess the echo-time (TE)-dependent signal in the labrum.
      RESULTS: The signal increase in the posterosuperior labrum was identified not
      only in the injured labra but also in nine of 10 intact labra. In the volunteers'
      studies, the signal in the posterosuperior labrum changed according to the
      examinees' positions (conventional supine or similar to Trendelenburg's) and
      according to TE. CONCLUSIONS: Increased signal intensity due to the magic-angle
      effect may be misdiagnosed as a labrum injury. Awareness of this pitfall is
      particularly important in MR imaging of throwing athletes whose posterosuperior
      labra are frequently injured by posterosuperior glenoid impingement.

PMID- 16082138
TI  - Motor denervation of tumors of the head and neck: changes in MR appearance.
AB  - PURPOSE: We reviewed the MR appearance of motor denervation of the third
      (mandibular) division of the trigeminal nerve (V3) and of the hypoglossal nerve.
      METHOD: Six cases of tumor of the head and neck with motor denervation were
      retrospectively evaluated. These comprised two patients with V3 denervation,
      three patients with hypoglossal nerve denervation, and one patient with both V3
      and hypoglossal denervation. The observation was conducted for 6 to 44 months
      after onset. In denervated muscles, changes in signal intensity in T(1)- and T(2)
      weighted images, degree of contrast enhancement, and volume of muscle were
      estimated during the follow-up period. RESULTS: In all cases of V3 denervation,
      the muscles showed no change in signal intensity in the T(1)-weighted images up
      to three months after onset. In two cases of hypoglossal denervation, the tongues
      appeared ipsilaterally hyperintense in the T(1)-weighted images within the first
      three months. In one case with V3 denervation and two cases with hypoglossal
      denervation, denervated muscles appeared hyperintense in the T(2)-weighted images
      up to three months after onset. At three months after denervation, the signal
      intensities of all motor-denervated areas increased in both T(1)- and T(2)
      weighted images. Postcontrast T(1)-weighted images obtained within the first
      three months displayed contrast enhancement of all denervated muscles. In three
      cases of V3 denervation, the volumes of the affected muscles were reduced after
      the first three months. In three cases of hypoglossal denervation, the
      ipsilateral volume of the tongue decreased at three months after onset.
      CONCLUSION: Up to three months after onset, the denervated muscles appeared
      hyperintense in the T(2)-weighted images and contrast enhancement in postcontrast
      T(1)-weighted images before fatty infiltration and volume loss were apparent.
      Familiarity with the MR appearance of denervated muscles accompanying tumors of
      the head and neck is important to avoid confusion with inflammatory or neoplastic
      processes.

PMID- 16082139
TI  - Gender difference in passive listening to stories: high-field fMRI study using
      multiple subject analysis based on individual activation maps.

PMID- 16082140
TI  - Serial amino-neurochemicals analysis in progressive lesion analysis of multiple
      sclerosis by magnetic resonance imaging and proton magnetic resonance
      spectroscopic imaging.

PMID- 16082141
TI  - Secondary degeneration of the substantia nigra and corticospinal tract after
      hemorrhagic middle cerebral artery infarction: diffusion-weighted MR findings.
AB  - Middle cerebral artery (MCA) infarction involving the striatum can cause
      secondary degeneration of the substantia nigra and corticospinal tract. We
      present a patient with subacute hemorrhagic MCA infarction in whom diffusion
      weighted MR images showed high signal intensity in the ipsilateral substantia
      nigra and corticospinal tract. A corresponding apparent diffusion coefficient map
      revealed a uniformly decreased signal in the same area. This represents secondary
      degeneration and should not be mistaken for other pathological conditions, such
      as a new infarction.

PMID- 16082142
TI  - Central neurocytoma with craniospinal dissemination.
AB  - We report a case of central neurocytoma that manifested tumor recurrence with
      craniospinal dissemination. Imaging studies before surgery showed a markedly
      enhanced tumor with small cysts and calcification, which invaded the adjacent
      brain parenchyma, located in the posterior horn of the right lateral ventricle.
      Proton MR spectroscopy showed markedly elevated choline and lactate peaks with a
      strongly diminished N-acetylaspartate peak. Two years after neurosurgical
      intervention, the tumor showed multiple craniospinal dissemination in the middle
      cranial fossa and the intradural extramedullary space of the spine.

PMID- 16082143
TI  - Cystic ovarian lesions in SSFP diffusion imaging.
AB  - PURPOSE: MR assessments of ovarian cystic lesions are usually based on
      morphological features, signal intensities and enhancement with contrast media.
      This study was performed to evaluate the usefulness of the steady-state free
      precession (SSFP) diffusion imaging of cystic ovarian lesions for analyzing
      cystic contents. MATERIALS AND METHODS: Sixty-one ovarian cystic lesions in 37
      patients were examined. The diffusion-related coefficient (DRC) and the ratio of
      the relative apparent diffusion coefficient of the lesion to that of subcutaneous
      fat tissue (rADC(L)/rADC(F)) were calculated from SSFP diffusion images. RESULTS:
      The DRCs and the rADC(L)/rADC(F) ratios in endometrial cysts and in the fatty
      parts of dermoid cysts were significantly lower than in other cystic tumors.
      CONCLUSION: SSFP diffusion imaging can be included in clinical practice to
      analyze ovarian cystic lesions within a short scan time; the DRC and the
      rADC(L)/rADC(F) ratio are useful for evaluating cystic contents.

PMID- 16082144
TI  - A new image navigation system for MR-guided cryosurgery.
AB  - PURPOSE: To evaluate the feasibility of Interactive Scan Control (ISC), a new MR
      image navigation system, during percutaneous puncture in cryosurgery. MATERIALS
      AND METHODS: With the ISC system in place, percutaneous MR-guided cryosurgery was
      performed in 26 cases, with the ISC system being used in 11 cases (five renal
      tumors, three uterine fibroids and three metastatic liver tumors). The ISC system
      comprised infrared cameras and an MR-compatible optical tracking tool that was
      directly connected to a cryoprobe. Tumor sizes ranged from 1.2 cm (metastatic
      liver tumor) to 9.0 cm (uterine fibroid), for a mean size of 3.9 cm. With ISC,
      one to three cryoprobes with a diameter of 2 mm or 3 mm were advanced into the
      tumors with the guidance of an MR fluoroscopic image. Two freeze-thaw cycles were
      used for cryosurgery. During the cryosurgery, the formation of iceballs was
      monitored on MR images. Follow-up dynamic CT or MRI as well as physical
      examinations were conducted after two weeks and six weeks. RESULTS: Placement of
      probes was successfully performed under the control of the ISC system. During
      cryosurgery, engulfment of the tumors by iceballs was carefully monitored by MRI.
      Necrosis of the cryoablated area was confirmed in all renal tumors by follow-up
      dynamic CT. The size regression of the uterine fibroids was observed through
      follow-up MRI. Two of the three cases of metastatic liver tumor were ablated
      completely. Additional therapy for a residual tumor was performed on one patient
      with a metastatic liver tumor. A small amount of pneumothorax was the only
      complication found in a patient with a metastatic liver tumor. CONCLUSION: MR
      guided cryosurgery with this new navigation system was feasible with low
      morbidity and allowed for safe and accurate puncture with a cryoprobe.

PMID- 16082145
TI  - Efficacy of dynamic MRI with superparamagnetic iron oxide (SH U 555 A):
      vascularity evaluation in hepatocellular carcinoma.
AB  - PURPOSE: A study was conducted to determine the possibility of evaluating the
      blood flow in cases of hypervascular hepatocellular carcinoma (HCC) by employing
      dynamic MRI with superparamagnetic iron oxide (SH U 555 A), which can be rapidly
      injected via an intravenous route. METHODS: Six patients with hypervascular HCC
      (23 nodules) served as the subjects. Dynamic MRI includes images obtained at
      precontrast and at 10 (perfusion phase), 60, 120, 180, 240, 300 and 600 s after
      the start of injection of SH U 555 A. CT hepatic arteriography (CTHA) and CT
      during arterial portography (CTAP) were used as the standards of reference, and
      these were performed in all patients three days after dynamic MRI. The signal
      changes were evaluated at each phase, especially at the perfusion phase from the
      viewpoints of a lesion-to-liver contrast-to-noise ratio (CNR) and visual
      examination. RESULTS: A total of 23 hypervascular HCC were detected on CTHA and
      CTAP. Of the 23 lesions, 17 were detected on SH U 555 A enhanced MRI. Incorrect
      timing during acquisition of the perfusion phase was considered in two cases with
      three lesions. Of 14 lesions, excluding two cases with incorrect timing, a
      reduction in the transient signal in the lesions at the perfusion phase was
      visually recognized in 10 lesions (71%). Significant differences were seen in
      tumor size between visible and non-visible tumors involving transient signal
      reduction (p< 0.05). CNR gradually increased after rapidly decreasing in the
      perfusion phase. CONCLUSION: SH U 555 A enhanced MRI is valuable in limited
      cases. Evaluation of tumor blood flow employing dynamic MRI with SH U 555 A is
      affected by tumor size and requires optimal timing of the perfusion phase.

PMID- 16082146
TI  - Adnexal masses caused by pelvic inflammatory disease: MR appearance.
AB  - PURPOSE: To describe the morphologic and signal intensity characteristics of
      inflammatory adnexal masses in magnetic resonance (MR) images. MATERIALS AND
      METHODS: MR images of 15 patients with a total of 20 confirmed inflammatory
      adnexal masses were analyzed retrospectively. RESULTS: The findings obtained from
      MR imaging were as follows: lesions have ill-defined borders; ill-defined areas
      of high intensity signals surround the masses on T(2)-weighted images; a "rim" at
      the innermost layer of the cyst wall exhibits high signal intensity on T(1)
      weighted images and low intensity on T(2)-weighted images; secondary changes in
      the surrounding fat plane and bowel loops are extensive; and adhesions are dense.
      These findings reflect the basic characteristics of the inflammatory process,
      which are edema caused by increased permeability and highly vascularized
      granulation tissue caused by the strong tendency to repair. CONCLUSION: MR
      imaging findings well reflect the basic pathological process of inflammation, and
      inflammatory adnexal masses are associated with relatively specific appearances
      in MR images. MR imaging can be a problem-solving alternative in the diagnosis of
      inflammatory adnexal masses.

PMID- 16082147
TI  - MR imaging in carotid artery atherosclerosis plaque characterization.
AB  - AIM: To evaluate the potential role of carotid artery atherosclerosis plaque
      magnetic resonance (MR) microimaging as magnetic resonance imaging (MRI) marker,
      ex vivo MR images were acquired at optimized parameters on 9.4T Bruker animal
      imager for occluded tissue resected by carotid endarterectomy (CEA) and
      corresponding histopathological analysis was made. METHODS AND MATERIALS: For
      imaging, CEA tissues of size 2-6 cm long and 0.5-1.5 cm wide, were transferred to
      15 ml co-polymer laboratory culture tubes containing either 10% formalin in
      phosphate buffered saline (PBS) or in 50% glycerol in PBS. Imaging protocol was
      set at TE=30 ms, TR=1.5 s, matrix size=265 x 512, NEX=128, slice thickness=1 mm
      and in-plane resolution=0.1 mm for total sample size 2.5 cm. Soon after imaging
      done, carotid artery tissues were cut into 5-mm segments and processed for
      histological section for successive 5-micrometer slices. To compare morphology of
      5 mum thin CEA section with that of 1 mm MR slices, registration was obtained
      between histologic sections and MR slices. Contrast and magnetic resonance
      relaxation characteristics were analyzed. RESULTS: Total carotid artery area
      computed by MR imaging was correlated with areas determined from histologic
      sections (r(2)=0.989, p=0.0001). For the lumen area, the correlation between MR
      images and histologic area was (r(2)=0.942, p=0.0001). Relaxation times and T(2)
      parametric images of different plaque components were determinant for contrast
      resolution. Scan parameters were optimized for fibrous cap and atheroma. Scan
      parameters were characteristic for comparison at 1.5T and 9.4T MR imagers.
      CONCLUSION: The observed correlation validated MR microimaging to assess
      morphological features of carotid artery plaques and contrast resolution
      highlighted the potential of in vivo MR imaging as non-invasive MRI marker to
      monitor carotid artery plaque morphometry and plaque composition.

PMID- 16082148
TI  - Nontraumatic aneurysm of a branch of the posterior tibial artery mimicking a
      schwannoma.
AB  - Aneurysms involving the infrapopliteal arteries are unusual and in most cases
      result from trauma. Nontraumatic aneurysms of the infrapopliteal arteries are
      very rare. We report a case of an aneurysm of a branch of the posterior tibial
      artery. The clinical manifestations and the findings from magnetic resonance
      imaging and computed tomography led us to make a preoperative diagnosis of
      schwannoma. Histologic examination of the excised specimen suggested that this
      lesion was likely a true aneurysm.

PMID- 16082149
TI  - Behcet's disease without neurological manifestations.

PMID- 16082150
TI  - Preventive strategies for aspiration pneumonia in elderly disabled persons.
AB  - Pneumonia is the fourth leading cause of death despite the availability of potent
      new antimicrobials in Japan. Aspiration of oropharyngeal bacterial pathogens to
      the lower respiratory tract is one of the most important risk factors for
      pneumonia. Impairments in swallowing and cough reflexes among disabled older
      persons, e.g., related to cerebrovascular disease, increase the risk of
      pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated
      material should be pursued. Since both swallowing and cough reflexes are mediated
      by endogenous substance P contained in the vagal and glossopharyngeal nerves,
      pharmacologic therapy using angiotensin-converting enzyme inhibitors, which
      decrease substance P catabolism, can improve both reflexes and result in the
      lowering of the risk of pneumonia. Similarly, since the production of substance P
      is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment
      with dopamine analogs or potentiating drugs such as amantadine can reduce the
      incidence of pneumonia. Furthermore, since mortality from infections correlates
      with cutaneous anergy, interventions that reverse these age-associated changes in
      the immune system are also effective. The main theme of this review is to discuss
      how pneumonia develops in disabled older people and to suggest preventive
      strategies that may reduce the incidence of pneumonia among these subjects.

PMID- 16082151
TI  - Influence of aging on cardiac function examined by echocardiography.
AB  - We assessed the influence of aging on cardiac function by means of parameters
      measured by echocardiography. The study group consisted of 494 normal subjects
      aged 13 to 87 years. We measured the ratio of early filling (E) and atrial
      contraction (A) transmitral flow velocities (E/A) of left and right ventricular
      inflow (LV E/A and RV E/A) for assessment of diastolic function. We also measured
      left ventricular ejection fraction (LVEF), and the ratio of pre-ejection period
      (PEP) and ejection time (ET) of the left ventricle (PEP/ET) for assessment of
      systolic function. Both LV E/A and RV E/A decreased significantly with aging
      while LVEF and PEP/ET remained normal range. The decline rate as aging was
      greater in LV E/A than in RV E/A. These results showed that both left and right
      ventricular diastolic function deteriorated with aging while left ventricular
      systolic function was not noticeably affected by aging. We suggest that indexes
      of diastolic function are more sensitive than those of systolic function when the
      natural course is studied in a large population.

PMID- 16082152
TI  - The prevalence of obesity and its relationship with lifestyle factors in Jamaica.
AB  - We surveyed the prevalence of obesity in the general population in Jamaica, and
      examined the relationship between it and lifestyle. The survey population
      consisted of 1,935 inhabitants in Jamaica, whose body weight, height, marital
      status, educational history, employment status and other obesity-associated
      lifestyle factors were surveyed. Six major findings emerged. The first finding is
      that the proportion of obesity in women was very high, and there was a big gender
      difference. Secondly, a lower prevalence towards obesity was associated with
      cohabitation of the subjects in both genders, and higher educational levels in
      female subjects. Thirdly, the proportion of the subjects who considered their
      weight to be quite acceptable was higher in the obese/overweight groups in both
      genders. Fourthly, exercise frequency showed a negative correlation with the body
      mass index (BMI) in men, and the frequency of exercising was apparently lower in
      women than in men. Fifthly, as for dietary factors, in both genders vegetables
      showed a negative correlation with the BMI. Sixthly, non-smokers were also
      associated with a lower obesity prevalence in men. In conclusions, these findings
      suggest that social and lifestyle factors such as the educational level, marital
      status and dietary habits of the general population influence Jamaican obesity.

PMID- 16082153
TI  - Fibrin stimulates the proliferation of human keratinocytes through the autocrine
      mechanism of transforming growth factor-alpha and epidermal growth factor
      receptor.
AB  - In the field of dermatology and plastic and reconstructive surgery, fibrin gel is
      regarded as a material that promotes wound healing. To test the hypothesis that
      fibrin may promote the growth of the epidermis, we examined its effects on the
      proliferation of cultured keratinocytes. Human keratinocytes were cultivated in
      fibrin-coated wells, and the cell numbers and transforming growth factor (TGF)
      alpha, secreted into the cultured medium, were measured. We also assessed the
      capacity of epidermal growth factor receptor (EGF-R) that is responsible for all
      known actions of TGF-alpha and epidermal growth factor. The keratinocytes
      increased dramatically in their number, and the TGF-alpha secretion and the
      binding capacity of EGF-R were also increased dramatically in the presence of
      fibrin. These findings suggest that fibrin supports the proliferation of
      keratinocytes in an autocrine fashion via EGF-R; namely, fibrin stimulates
      keratinocytes to secrete TGF-alpha, which in turn increases cell proliferation
      and EGF-R capacity. We propose that fibrin can support the wound healing process
      of the epidermis via the TGF-alpha/EGF-R pathway.

PMID- 16082154
TI  - Prevalence of chronic obstructive pulmonary disease in Japanese people on medical
      check-up.
AB  - In Japan, spirometry has not been included as an item in medical check-ups for
      all persons. The purpose of this study was to show evidence to recommend
      spirometry routinely on medical check-up for the early detection of chronic
      obstructive pulmonary disease (COPD). There were 12,760 enrolled persons who
      underwent medical check-up. COPD was defined as a ratio of forced expiratory
      volume in one second to slow vital capacity of 70% or less. We investigated the
      prevalence and its characteristics of COPD in people on medical check-up. The
      prevalence of COPD was 3.6% in all subjects, 4.5% in males, and 1.8% in females.
      In the comparison between males and females, the prevalence of COPD in males of
      most age groups was higher than that of females, and this difference was greater
      with aging. Males in their 50s and over 60 years old and females over 60 years
      old showed remarkably high prevalences. Occupations associated with a high
      smoking rate such as transportation-related occupations showed a higher
      prevalence of COPD. These results suggest that spirometry for all persons in
      medical check-ups can identify many COPD patients not aware of this disease.
      Spirometry should be carried out routinely on medical check-up.

PMID- 16082155
TI  - Efficiency of prostacyclin in the treatment of protamine-mediated right
      ventricular failure and acute pulmonary hypertension.
AB  - Protamine is used after cardiopulmonary bypass was stopped in order to reverse
      the anticoagulant effects of heparin administered during open-heart operations.
      Adverse hemodynamic responses to protamine are common, ranging from minor
      perturbations to cardiovascular collapse. The aim of the present study was to
      investigate whether a prostacyclin is effective in the treatment of protamine
      mediated acute pulmonary hypertension and right ventricular failure in the
      perioperative period of isolated coronary artery bypass grafting (CABG)
      operations. In sixty-eight (1.78%) of 3800 patients who underwent isolated CABG,
      acute pulmonary hypertension and right ventricular failure developed during or
      following the protamine infusion. These 68 patients were included in the study
      and were randomized into two groups. Thirty-eight of the patients received
      prostaglandin I(2) (PGI(2)), norepinephrine and dopamine (PGI(2) group), whereas
      30 patients received nitroglycerin, norepinephrine and dopamine (control group).
      Hemodynamic data were recorded before and after the above drug combinations. The
      mean value of left ventricle ejection fraction significantly increased (p < 0.05)
      and mean values of central venous pressure, pulmonary artery systolic and
      diastolic pressure, pulmonary capillary wedge pressure and pulmonary vascular
      resistance significantly decreased (p < 0.05) in the PGI(2) group. The mean value
      of pulmonary capillary wedge pressure significantly decreased (p < 0.05) and the
      mean value of central venous pressure significantly increased (p < 0.05) in the
      control group. In conclusion, prostacyclin (PGI(2)) is effective in the treatment
      of protamine-mediated acute pulmonary hypertension and right ventricular failure
      in the perioperative period in isolated CABG operations. This finding may be an
      important contribution to the treatment of severe protamine complications during
      open-heart operations.

PMID- 16082156
TI  - High frequency of aspirin resistance in patients with acute coronary syndrome.
AB  - Aspirin is widely used for secondary prevention of cardiovascular disease, but is
      not effective for all patients. This phenomenon is called as aspirin resistance.
      Although the prognosis is worse in patients who develop acute coronary syndrome
      (ACS) while using aspirin, the frequency of aspirin resistance in these patients
      has not been evaluated. We aimed to evaluate the frequency of aspirin resistance
      in patients with ACS and to determine its relationship with the angiographic
      severity and extent of the associated coronary artery disease. The present study
      included 104 patients with ACS (75 men, 60.4 +/- 10.8 years) who were
      hospitalized while using aspirin for at least last 7 days and 100 patients with
      stable coronary artery disease (73 men, 57.6 +/- 10.6 years), documented by
      coronary angiography, history of revascularization or myocardial infarction (MI),
      and the use of aspirin for last 7 days. The latter group had no MI or ACS for
      last 3 months. Platelet function was assessed with PFA-100, which simulates
      primary homeostasis at injured blood vessels. Coronary angiography was performed
      in 83 cases of the patients with ACS during hospital stay. Aspirin resistance is
      more prevalent in patients with ACS (40.3%) when compared with stable coronary
      artery disease patients (27%). The difference was statistically significant (p =
      0.04). The ACS patients with aspirin resistance were older and had severe
      myocardial damage. However, there were no significant differences in angiographic
      severity and extent of coronary artery disease between aspirin-resistant and
      aspirin-sensitive patients. Frequency of aspirin resistance is higher in patients
      who develop ACS while using aspirin than that in patients with stable coronary
      artery disease.

PMID- 16082157
TI  - Diagnostic value of the serum platelet-activating factor acetylhydrolase activity
      in inflammatory bowel disease.
AB  - Platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme hydrolyzing
      platelet-activating factor (PAF), a potent inflammatory mediator, but the
      relationship between this enzyme and inflammatory bowel disease (IBD) is not
      fully elucidated. The aim of the present study was to examine the usefulness of
      the serum PAF-AH activity in order to differentiate ulcerative colitis (UC) from
      Crohn's disease (CD). The serum PAF-AH activity was measured in 57 patients with
      IBD (39 UC and 18 CD patients) and 13 control subjects by a spectrophotometric
      method. The serum PAF-AH activity was thus found to be significantly lower in
      patients with CD (median 265.5 U/l) than in those with UC (355 U/l) or control
      subjects (374 U/l). This marker at a cutoff level of 386 U/l demonstrated a
      sensitivity of 46%, a specificity of 100%, and a positive predictive value of
      100% regarding its ability to distinguish UC from CD. Moreover, the marker
      responded inversely to the changes in the disease activity of IBD. These results
      suggest that measuring the serum PAF-AH activity is a useful diagnostic modality
      for making a differential diagnosis between UC and CD.

PMID- 16082158
TI  - A survey of restaurant smoking restrictions in a Japanese city.
AB  - Japan has been behind the times in terms of promoting smoking control. The health
      promotion law, which included the aim of preventing environmental tobacco smoke
      (ETS) in public places, was newly introduced in Japan in 2003. The community
      based survey on the present state of restaurant smoking restrictions and
      restaurant owners' concern of smoking is important as it is a reflection of the
      community's desire to prevent ETS. Data on the smoking restrictions in 163
      restaurants in Yonago, one Japanese community, and the owners' smoking-related
      awareness were collected just one month after the law was enacted. This study
      revealed that only 6 (3.6%) restaurants were under sufficient conditions: 3 with
      totally smoke-free and 3 with complete non-smoking sections. The styles (e.g.,
      Western-, Japanese- and Chinese-styles) and kinds of restaurants (e.g., family
      restaurants and tearooms) were not related to the state of smoking restrictions.
      Rates of smokers were relatively high among owners, and smoking owners
      significantly provided insufficient smoking restrictions. 26.4% of owners knew
      about the new law. However, there were no restaurants that started their smoking
      restrictions due to the law. Owners' knowledge of the law did not correlate with
      smoking restrictions. The owners especially feared the negative effects on
      business due to smoking restrictions. These survey findings suggested little
      protection from ETS in a sample of restaurants and a large gap in restaurant
      smoking restrictions compared to other countries. More widespread adoption of the
      health-promotion law in restaurants is an issue.

PMID- 16082159
TI  - Unique cerebellar-cerebral form of autosomal recessive ataxia.
AB  - We describe a unique condition affecting two siblings with a form of progressive
      spinocerebellar ataxia. After a period of very slowly progressive ataxia, the
      patients developed an extremely accelerated progression of the condition which
      consisted of cerebellar ataxia, seizure, progressive dementia and spastic
      tetraparesis. Age of onset was variable at 7 to 18 years. Brain magnetic
      resonance image (MRI) showed marked atrophy of the cerebellum and cerebrum with
      strikingly preserved brainstem dimensions. Biochemical or molecular genetic
      analysis was performed in an elder sister and her parents to exclude known forms
      of familial spinocerebellar ataxia, dentatorubral-pallidoluysian atrophy (DRPLA),
      progressive myoclonic epilepsy, and some metabolic disorders which could have a
      similar phenotype. The mode of inheritance appears to be autosomal recessive. We
      think that the affected siblings may have a new type of autosomal recessive
      cerebellar ataxia.

PMID- 16082160
TI  - Exploring the mechanisms causing a high allometric value of female pleopod in the
      crayfish Procambarus clarkii.
AB  - Female pleopods in Procambarus clarkii have a function of holding eggs, and their
      length shows positive allometry. It is likely that the positive allometry has
      resulted from directional selection in terms of egg holding ability. Firstly, we
      examined the allometry of reproductive potential (ovarian egg number). The
      allometric value of reproductive potential was lower than that of pleopod length,
      which indicates that the positive allometry of pleopod length is not merely the
      reflection of the allometry of reproductive potential. Secondly, we examined the
      relationship between the relative length of pleopod and egg holding ability to
      test the presence of directional selection on the pleopod length, and then
      compared the strength of the directional selection between the individuals
      differing in their body sizes to infer the mechanisms causing the positive
      allometry for female pleopods. There was a positive relationship between relative
      pleopod length and relative egg mass remaining to the pleopod, and this
      relationship was stronger in small individuals. These relationships were not
      merely the reflection of relationship between pleopod length and reproductive
      potential. These results indicate that directional selection was acting on the
      length of female pleopods, and the strength of the directional selection was
      stronger in smaller individuals. Therefore, it appears that the positive
      allometry of female pleopods in P. clarkii has been caused by the constraint for
      possessing longer pleopods in small individuals, although the mechanisms of the
      constraint remain unknown.

PMID- 16082161
TI  - A genome-wide survey of genes for enzymes involved in pigment synthesis in an
      ascidian, Ciona intestinalis.
AB  - The draft genome sequence and a large quantity of EST and cDNA information are
      now available for the ascidian Ciona intestinalis. In the present study, genes
      involved in pigment synthesis pathways were identified in the decoded genome of
      Ciona, and information about these genes was obtained from available EST and cDNA
      sequences. It was found that the Ciona genome contains orthologous genes for each
      enzyme of the melanin, pteridine, ommochrome, papiliochrome, and heme synthesis
      pathways. Several appear as independent duplications in the Ciona genome. Because
      cDNA clones for all but two of these genes have already been isolated by the cDNA
      project, C. intestinalis will provide an experimental system to explore molecular
      mechanisms underlying color patterns, through future genome-wide studies.

PMID- 16082162
TI  - Amphipathic alpha-helix mediates the heterodimerization of soluble guanylyl
      cyclase.
AB  - Soluble guanylyl cyclase (soluble GC) is an enzyme consisting of alpha and beta
      subunits and catalyzes the conversion of GTP to cGMP. The formation of the
      heterodimer is essential for the activity of soluble GC. Each subunit of soluble
      GC has been shown to comprize three functionally different parts: a C-terminal
      catalytic domain, a central dimerization domain, and an N-terminal regulatory
      domain. The central dimerization domain of the beta(1) subunit, which contains an
      N-terminal binding site (NBS) and a C-terminal binding site (CBS), has been
      postulated to be responsible for the formation of alpha/ beta heterodimer. In
      this study, we analyzed heterodimerization by the pull-down assay using the
      affinity between a histidine tag and Ni(2+) Sepharose after co-expression of
      various N- and C-terminally truncated FLAG-tagged mutants of the alpha(1) subunit
      and the histidine-tagged wild type of the beta(1) subunit in the vaculovirus/Sf9
      system, and demonstrated that the CBS-like sequence of the alpha(1) subunit is
      critical for the formation of the heterodimer with the beta(1) subunit and the
      NBS-like sequence of the alpha(1) subunit is essential for the formation of the
      enzymatically active heterodimer, although this particular sequence was not
      involved in heterodimerization. The analysis of the secondary structure of the
      alpha(1) subunit predicted the existence of an amphipathic alpha-helix in
      residues 431-464. Experiments with site-directed alpha(1) subunit mutant proteins
      demonstrated that the amphipathicity of the alpha-helix is important for the
      formation of the heterodimer, and Leu(463) in the alpha-helix region plays a
      critical role in the formation of a properly arranged active center in the dimer.

PMID- 16082163
TI  - Postembryonic development of the mushroom bodies in the ant, Camponotus
      japonicus.
AB  - Mushroom bodies (MB) are insect brain centers involved in learning and other
      complex behaviors and they are particularly large in ants. We describe the larval
      and pupal development of the MB in the carpenter ant, Camponotus japonicus. Based
      on morphological cues, we characterized the stages of preimaginal development of
      worker ants. We then describe morphological changes and neurogenesis underlying
      the MB development. Kenyon cells are produced in a proliferation cluster formed
      by symmetrical division of MB neuroblasts. While the duration of larval instars
      shows great individual variation, MB neuroblasts increase in number in each
      successive larval instar. The number of neuroblasts increases further during
      prepupal stages and peaks during early pupal stages. It decreases rapidly, and
      then neurogenesis generally ceases during the mid pupal stage (P4). In contrast
      to the larval period, the MB development of individuals is highly synchronized
      with physical time throughout metamorphosis. We show that carpenter ants (C.
      japonicus) have approximately half as many MB neuroblasts than are found in the
      honey bee Apis mellifera. Mature MBs of carpenter ants and honey bees reportedly
      comprise almost the same number of neurons. We therefore suggest that the MB
      neuroblasts in C. japonicus divide more often in order to produce a final number
      of MB neurons similar to that of honey bees.

PMID- 16082164
TI  - Induction of cells expressing vascular endothelium markers from undifferentiated
      Xenopus presumptive ectoderm by co-treatment with activin and angiopoietin-2.
AB  - Activin is a potent inducer of mesoderm in amphibian embryos. We previously
      reported that low concentrations of activin could induce the formation of blood
      cells from Xenopus explants (animal caps). Both hematopoietic and vascular
      endothelial cell lineages are believed to share a common precursor, termed
      hemangioblasts. In this study, we tried to induce differentiation of vascular
      endothelial cells in aggregates derived from Xenopus animal caps. Aggregates
      formed from cells that were co-treated with activin and angiopoietin-2 expressed
      the vascular endothelial markers, X-msr, Xtie2 and Xegfl7. However, none of these
      aggregates expressed the hematopoietic marker genes, globin alpha T3, alpha T5,
      alpha A or GATA-1. We used microarray analysis to compare the gene expression
      profiles of aggregates treated with activin alone or with activin and
      angiopoietin. The combination, but not activin alone, induced expression of
      vascular-related genes such as Xl-fli and VEGF. These results demonstrate that
      treatment of dissociated animal cap cells with activin and angiopoietin-2 can
      induce differentiation of endothelial cells, and provides a promising model
      system for the in vitro study of blood vessel induction in vertebrates.

PMID- 16082165
TI  - Effects of photoperiod, melatonin, and the pineal gland on compensatory gonadal
      hypertrophy during postnatal development in the marsh rice rat (Oryzomys
      palustris).
AB  - The roles of photoperiod, melatonin, and the pineal gland in regulating the
      magnitude of compensatory gonadal hypertrophy (CGH) and other reproductive and
      non-reproductive organ growth during post-weaning development were examined in
      the marsh rice rat Oryzomys palustris. Juvenile rice rats of both sexes were left
      gonadally intact (control group) or unilaterally castrated (ULC) and housed on
      12L:12D, 14L:10D, or 16L:8D. Within a photoperiod (14L:10D and 16L:8D, but not
      12L:12D), growth of the remaining testis, but not the remaining ovary, as well as
      several additional organs in both sexes were significantly affected, suggesting
      that the compensatory hypertrophy of the testis is photoperiod-dependent. There
      was no effect of testis asymmetry on CGH as ULC of either testis in rice rats
      housed on 14L:10D resulted in a comparable increase of CGH. Melatonin implants in
      rice rats maintained on 16L:8D had little to no effect (CGH included) on most
      parameters examined. Both melatonin implants and pinealectomy (separate
      experiments) in rice rats transferred to 12L:12D prevented short photoperiod
      induced effects on CGH, the growth of the reproductive organs and the Harderian
      glands. Evening melatonin injections had a significant inhibitory effect on the
      growth of the remaining testis (no CGH was observed) and all other parameters
      measured. Lastly, ULC did not alter the percentage of males which successfully
      mated compared to intact animals. Taken together, these data suggest that
      photoperiod, melatonin, and the pineal gland can affect and regulate reproductive
      (e.g., CGH in some cases) and non-reproductive growth during postnatal
      development in the marsh rice rat.

PMID- 16082166
TI  - Neuroendocrine roles of the brain in the regulation of 20-hydroxyecdysone
      responsiveness in two types of diapause pupae of the cabbage armyworm, Mamestra
      brassicae.
AB  - The cabbage armyworm, Mamestra brassicae, has winter-and aestival- diapause pupae
      (WD- and AD-pupae) showing differences in the strength of diapause. We tried to
      quantify diapause-strength by measuring the doses of 20-hydroxyecdysone (20-E)
      required to induce adult development in WD-, AD- and decerebrated non-diapause
      pupae (ND-pupae). The role of the brain in the regulation of diapause-strength
      was studied through the decerebration and brain-reimplantation of WD-and AD
      pupae. The 20-E doses required for adult development were small within the first
      2 days of pupation, and increased thereafter to reach a constant level about 10
      days after pupation in AD- and decerebrated ND-pupae. The required 20-E doses in
      WD-pupae increased for more than 40 days after pupation. When 0-day-old WD- and 0
      day-old AD-pupae were decerebrated, required 20-E doses increased after pupation
      and reached a constant about 10 days later. The required 20-E dose reached a
      constant level in decerebrated WD-pupae that was smaller than that observed for
      decerebrated ND- and WD-pupae. Furthermore, the required doses increased when 0
      day-old WD-pupal brains were reimplanted into decerebrated WD- and decerebrated
      ND-pupae. In WD-, AD- and decerebrated ND-pupae, diapause-strength can be
      represented as the 20-E dose required for adult development. Diapause-strength is
      weak after pupation, increases thereafter, and reaches a constant about 10 days
      later in AD- and decerebrated ND-pupae. In WD-pupae, diapause-strength increases
      for more than 40 days after pupation and reaches a level that is twice that
      estimated for AD-pupae. Brains of diapausing WD-pupae may secrete a factor that
      suppresses the 20-E responsiveness of pupal organs, for the purpose of
      maintaining winter-diapause.

PMID- 16082167
TI  - Electron microscopic study of the anterior midgut in Cenocorixa bifida Hung.
      (Hemiptera: Corixidae) with reference to its secretory function.
AB  - The epithelium of anterior midgut of adult Cenocorixa bifida was examined with
      light and electron microscopy. The folded epithelium is composed of tall columnar
      cells extending to the lumen, differentiating dark and light cells with
      interdigitating apices and regenerative basal cells in the nidi surrounded by
      villiform ridges that penetrate deeply into the epithelium. The columnar cells
      display microvilli at their luminal surface. Microvilli lined intercellular
      spaces and basal plasma membrane infoldings are associated with mitochondria.
      These ultrastructural features suggest their role in absorption of electrolytes
      and nutrients from the midgut lumen. The columnar cells contain large oval nuclei
      with prominent nucleoli. Their cytoplasm is rich in rough endoplasmic reticulum,
      Golgi complexes and electron-dense secretory granules indicating that they are
      also engaged in synthesis of digestive enzymes. The presence of secretory
      granules in close proximity of the apical plasma membrane suggests the release of
      secretion is by exocytosis. The presence of degenerating cells containing
      secretory granules at the luminal surface and the occurance of empty vesicles and
      cell fragments in the lumen are consistent with the holocrine secretion of
      digestive enzymes. Apical extrusions of columnar cells filled with fine granular
      material are most likely formed in response to the lack of food in the midgut.
      The presence of laminated concretions in the cytoplasm is indicative of
      storageexcretion of surplus minerals. The peritrophic membrane is absent from the
      midgut of C. bifida.

PMID- 16082168
TI  - Effects of estradiol-17beta on germ cell proliferation and DMY expression during
      early sexual differentiation of the medaka Oryzias latipes.
AB  - Sex reversal of XY male to functional females was induced by estrogen treatment
      during the embryonic period in the medaka Oryzias latipes. The present study
      aimed to examine whether exogenous estrogen (estradiol-17beta; E(2)) affects
      early sex differentiation, paying particular attention to DMY expression and
      proliferation activity of germ cells in estrogen treated XY individuals. Our
      results showed that germ cell number was not affected by E(2) treatment at
      hatching, and that DMY expression was not suppressed under conditions of sex
      reversal. Therefore, male differentiation of germ cells, which is triggered by
      the expression of DMY in the supporting cell lineage, proceeds even in E(2)
      treated XY individuals until hatching, and early sex differentiation is not
      altered by estrogen. However, sex reversal occurred after hatching probably
      because of estrogen remaining in the yolk. Interestingly, DMY expression was also
      detected in the large follicle layer of E(2 )treated XY ovary. These results
      suggested that DMY regulates male determination in early embryonic stage but does
      not suppress female follicle development.

PMID- 16082169
TI  - Bi-directional sex change in coral reef fishes from the family Pseudochromidae:
      an experimental evaluation.
AB  - Coral reef fishes exhibit a diversity of hermaphroditic strategies and
      comparisons among species with different ecological characteristics will help
      identify the underlying basis of this complexity. We used manipulative
      experiments to test the potential for bi-directional sex change in three species
      of Pseudochromis (Pseudochromidae): P. flavivertex, P. aldabraensis and P.
      cyanotaenia. The first two species are sexually monochromatic, whereas, P.
      cyanotaenia is sexually dichromatic. For each species, where two functional
      females were kept together, one individual in the pair changed sex to male. Where
      two functional males were kept together, one individual in the pair changed sex
      to female. In all three species, functional sex change from male to female (52-93
      days) took longer than sex change from female to male (18-56 days). In the
      sexually dichromatic species, P. cyanotaenia, colour change accompanied adult sex
      change. Females that changed sex to male took on the bright colouration of males
      and males that changed sex to female took on the drab colouration of females.
      These results indicate that bi-directional sex change is probably widespread in
      the family Pseudochromidae and cannot be predicted by the presence or absence of
      secondary sexual characteristics.

PMID- 16082170
TI  - Karyotype of a Japanese salamander Hynobius katoi and its implication on breeding
      ecology (Amphibia: Caudata).
AB  - Karyotype of a Japanese small salamander, Hynobius katoi, was first described.
      All individuals examined had 2n=58 chromosomes, consisting of nine pairs of
      biarmed macrochromosomes, four pairs of biarmed medium-sized chromosomes, six
      pairs of biarmed microchromosomes, and 10 pairs of uniarmed microchromosomes,
      although distinction of the second and the third groups of chromosome pairs was
      not clear. All pairs appeared homologous and no sexual dimorphism was found.
      Possession of 2n=58 chromosomes in H. katoi strongly suggests its lotic-breeding
      habits as was expected from the number and size of eggs and adult morphology.
      When compared morphology of chromosomes among lotic-breeders with 2n=58
      chromosomes, metacentric nature of No. 10 seems to characterize the karyotype of
      H. katoi.

PMID- 16082171
TI  - A new Ansonia from the Isthmus of Kra, Thailand (Amphibia, Anura, Bufonidae).
AB  - A new species of torrent-dwelling bufonid frog of the genus Ansonia is described
      from the Isthmus of Kra, Thailand. Ansonia kraensis is morphologically similar to
      Malaysian A. malayana, but differs from it in ventral coloration and larval
      morphology. Occurrence of A. kraensis in this region suggests a heterogeneous
      nature of the anuran fauna between northern and southern regions of the Malay
      Peninsula.

PMID- 16082172
TI  - The mRNA expression differences of RNA editing enzymes in differentiated and
      undifferentiated NG108-15 cells.
AB  - The alteration of the editing pattern of serotonin 2C receptor (5-HT2CR) mRNA has
      been reported during cell differentiation. Since editing of 5-HT2CR mRNA is
      regulated by adenosine deaminases acting on RNA (ADARs), it is of interest to
      investigate if the expression of these enzymes changes during cell
      differentiation. The level of ADAR1 mRNA in NG108-15 cells was decreased by cell
      differentiation. These results suggest that the decrease of ADAR1 expression
      during cell differentiation may play an important role in the differentiation
      induced alteration of the 5-HT2CR editing pattern in NG108-15.

PMID- 16082173
TI  - Maternal alcohol administration suppresses expression of nitric oxide synthase in
      the hippocampus of offspring rats.
AB  - Maternal alcohol consumption during pregnancy can produce teratogenic effects and
      has a detrimental effect on the development of the fetus. In this study, the dose
      dependent effect of maternal alcohol administration on the expression of nitric
      oxide synthase (NOS) in the hippocampus of the offspring rats was investigated.
      From the present result, it was shown that expression of NOS is decreased
      following treatment with maternal alcohol in a dose-dependent fashion. The
      present results suggest that suppression of NOS expression in the hippocampus of
      offspring rats with maternal alcohol mediates the associated developmental
      retardation and/or anomalies.

PMID- 16082174
TI  - Effects of [5-(2-methoxy-5-fluorophenyl)furan-2-ylcarbonyl]guanidine (KR-32560),
      a novel sodium/hydrogen exchanger-1 inhibitor, on myocardial infarct size and
      ventricular arrhythmias in a rat model of ischemia/reperfusion heart injury.
AB  - The cardioprotective effects of the novel sodium/hydrogen exchanger-1 (NHE-1)
      inhibitor KR-32560 {[5-(2-methoxy-5-fluorophenyl)furan-2-ylcarbonyl]guanidine}
      were studied in an anesthetized rat model of 30-min ischemia / 2.5-h reperfusion
      heart injury. KR-32560 (0.01 - 1 microM) dose-dependently inhibited NHE-1
      mediated rabbit platelet swelling induced by intracellular acidification. KR
      32560 at 0.1 and 1.0 mg/kg (i.v. bolus, given 10 min before ischemia) reduced
      infarct size from 65.9% (control) to 49.7% and 32.7%, respectively, while
      reducing the extension of myocardial injury (mm(3)/g of left heart weight) from
      405.1 (control) to 302.9 and 185.4, respectively (all P<0.05 vs control). KR
      32560 dose-dependently reduced the total number of ventricular premature beats
      (VPBs) during ischemia from 510.2 (control) to 353.8 and 134.2 beats (all P<0.05,
      n = 6), while reducing ventricular tachycardia (VT) incidence from 49.3 (control)
      to 26.8 and 4.3 and VT duration from 249.2 s (control) to 150.5 and 26.7 s (all
      P<0.05, n = 6). KR-32560 dose-dependently reduced ventricular fibrillation (VF)
      incidence from 19.0 (control) to 9.2 and 1.2 and VF duration from 88.0 s to 34.5
      and 2.8 s (all P<0.05, n = 6). KR-32560 also exerted similar effects on
      reperfusion arrhythmias, except for VPBs. These results indicate that KR-32560
      may exert significant cardioprotective effects in ischemia/reperfusion heart
      injury.

PMID- 16082175
TI  - Simple and noninvasive breath test using 13C-acetic acid to evaluate gastric
      emptying in conscious rats and its validation by metoclopramide.
AB  - The (13)C-breath test has been used to clinically evaluate gastric emptying.
      However, this method has not been sufficiently validated in experimental animals.
      The present study aimed to establish a simple and noninvasive (13)C-breath-test
      system in Sprague-Dawley male rats. After fasting, rats were orally administered
      Racol containing (13)C-acetic acid and housed in a desiccator. The expired air in
      the chamber was collected in a breath-sampling bag using a tube and aspiration
      pump. The level of (13)CO2 in the expired air was measured using an infrared
      spectrometer at appropriate intervals for 120 min. During this period, the rate
      of (13)CO2 excretion increased, peaked, and decreased thereafter. The maximum
      concentration (Cmax) and area under the curve (AUC120 min) of (13)CO2 excretion
      increased in volume- and dose-dependent manners. The time taken to reach the
      maximum concentration (Tmax) of (13)CO2 excretion increased as the volume
      increased, but was not affected by the dose of (13)C-labeled acetic acid.
      Metoclopramide dose-dependently increased the Cmax and shortened Tmax of (13)CO2
      excretion compared with those of the control rats, whereas the AUC120 min was not
      affected. These results confirm that this simple method can successfully evaluate
      gastric emptying. Moreover, this system is suitable for investigating additional
      physiological functions using other labeled compounds.

PMID- 16082176
TI  - Quantifying receptor properties: the tissue segment binding method - a powerful
      tool for the pharmacome analysis of native receptors.
AB  - The radioligand binding assay technique is an extremely powerful tool for
      studying receptors. It allows an analysis of the interactions of hormones,
      neurotransmitters, and related drugs with their receptors. Most of the binding
      assays have widely been applied to crude membrane fractions prepared from many
      tissues, but in the conventional method, there are some limitations such as a
      yield loss of receptor-bearing membranes and a change in receptor environment
      upon homogenization and fractionation. Recently, in order to overcome these
      problems, a binding assay has been developed using intact tissue segments. This
      article presents a brief overview of the tissue segment binding assay that has
      been developed mainly in our department. Practical guidelines for setting up this
      new assay are presented, including segment preparation, choice of appropriate
      radioligand, optimizing assay conditions, and appropriate methods for data
      analysis. The unique advantages and disadvantages of the tissue segment binding
      method are discussed in comparison with those of conventional membrane binding
      methods. We suggest that the tissue segment binding method is a powerful tool for
      detecting the native properties of receptors occurring in tissues and cells
      without altering their environment.

PMID- 16082177
TI  - Absence of specific cell killing of the BRCA2-deficient human cancer cell line
      CAPAN1 by poly(ADP-ribose) polymerase inhibition.
AB  - The specific killing of cells impaired in BRCA2 function upon treatment with poly
      (ADP-ribose) polymerase (PARP) inhibitors has recently been reported by two
      groups. CAPAN1, which was not characterized in these reports, represents the only
      human cancer cell line harboring the frequent, naturally occurring BRCA2 6174delT
      frameshift mutation accompanied by loss of the second allele. The severe impact
      of this mutation on BRCA2 function has been extensively characterized. However,
      PARP inhibition by 3-aminobenzamide or NU1025 did not result in significant cell
      death in CAPAN1 cells. Our data raise concern about the uniformity of the
      specific cell killing of BRCA2-deficient cells upon PARP inhibition and therefore
      urge caution as to whether prior findings are fully generalizable for the
      specific treatment of human cancers harboring naturally occurring, inactivating
      forms of BRCA2 mutations.

PMID- 16082178
TI  - The histone deacetylase inhibitor, Trichostatin A, enhances radiation sensitivity
      and accumulation of gammaH2A.X.
AB  - Histone deacetylase inhibitors have been shown to induce numerous biologic
      effects including, altering cell cycle distribution, cytostasis and in certain
      cases apoptosis. Given their ability to disrupt critical biological processes in
      cancer cells, these agents are emerging as potential therapeutics for cancer.
      Recently, it has been identified that histone deacetylase inhibitors can also
      efficiently enhance the radiation sensitivity of cells, both in vitro and in
      vivo. In this study, we investigated whether the potent histone deacetylase
      inhibitor, Trichostatin A, modulates the radiation sensitivity of human
      erythroleukemic K562 cells. The endpoints we used were clonogenic survival,
      apoptosis and gammaH2AX immunoprecipitations of soluble chromatin. The findings
      from clonogenic survival assays indicated that incubation with Trichostatin A 24
      hours prior to irradiation enhances the radiation sensitivity of K562 cells. The
      dose modification factors ranged from 1.1 when cells were incubated with 0.1
      microM Trichostatin A to 2.3 at 1 microM Trichostatin A. Similarly, caspase-3 and
      caspase-7 assays indicated that Trichostatin A potentiates radiation-induced
      apoptosis in K562 cells, in a concentration dependent manner. Our results suggest
      the modulation of radiation effects observed at the lower Trichostatin A
      concentrations was associated with histone hyperacetylation and changes in
      phosphorylated gammaH2A.X formation on euchromatin. In contrast, at the higher
      Trichostatin A concentrations mechanisms such as drug-mediated cytotoxicity and
      G1 cell cycle arrest, contributed to the sensitization effect. More generally,
      our findings are consistent with those from recent studies and support the
      development of histone deacetylase inhibitors for use as radiation sensitizers,
      particularly for targeting radioresistant cancers.

PMID- 16082179
TI  - PPARgamma as a therapeutic target for tumor angiogenesis and metastasis.
AB  - Peroxisome proliferator activated receptors (PPARs) are ligand-activated
      transcription factors with pleiotropic effects on cell fate and metabolism.
      Because of its anti-proliferative, pro-apoptotic and differentiation promoting
      activities, PPARgamma has been intensively evaluated as a target for anti-cancer
      therapy in preclinical models. However, PPARgamma has been reported to act both
      as a promoter and suppressor of neoplasia, and the role of PPARgamma activating
      ligands as well as antagonists in therapy remains controversial. In the past
      decade a new picture of tumors as a disease that involves changes in the non
      cancerous tumor bed, including angiogenesis, inflammation and other stromal
      changes has emerged. PPARgamma has strong anti-inflammatory and anti-angiogenic
      effects, extending the repertoire of potential targets of PPARgamma ligands
      beyond cell autonomous mechanisms of cancer. The heterogeneous cellular targets
      and the biphasic effects of PPARgamma on various pro and anti-tumor processes may
      account for the apparent paradoxical effects of PPARgamma agonists. Here we
      review the action of PPARgamma agonists on angiogenesis and inflammation in the
      context of tumorigenesis as an integrated tissue process and discuss potential
      explanations for the conflicting effects of PPARgamma agonists on tumor
      progression and metastasis. Sorting out the various modes of action and defining
      their relative contribution in the context of tumor and host tissue as a
      heterogeneous target will therefore be crucial to understand the multi facetted
      effects of PPARgamma. This will be paramount if the potent biological activity of
      PPARgamma agonists are to be harnessed for cancer therapy.

PMID- 16082180
TI  - Seeking favors from nature.

PMID- 16082181
TI  - Lymphocyte life and death: the caspase-8 connection.
AB  - Caspase-8 plays an important role in death receptor-mediated apoptosis. In
      contrast to its apoptotic function, recent studies have suggested caspase-8 also
      plays a role in the immune response, as caspase-8 is essential for lymphocyte
      proliferation in response to antigen stimulation. In the March 2005 issue of
      Science (2005; 307:1465-8), Su et al. provide compelling evidence supporting a
      role for caspase-8 in antigen receptor-induced NF-kappaB activation. They
      identified caspase-8 as an essential component in the activation of the IKK
      complex, linking IKK to the upstream Bcl10-MALT1 complex. Intriguingly, they
      demonstrated that it is not only the physical presence of caspase-8, but rather
      enzymatic activity that is required for the activation of NF-kappaB.

PMID- 16082182
TI  - Proteasome inhibitors-mediated TRAIL resensitization and Bik accumulation.
AB  - Proteasome inhibitors can resensitize cells that are resistant to tumor necrosis
      factor-related apoptotic-inducing ligand (TRAIL)-mediated apoptosis. However, the
      underlying mechanisms of this effect are unclear. To characterize the mechanisms
      of interaction between proteasome inhibitors and TRAIL protein, we evaluated the
      effects of combined treatment with the proteasome inhibitors bortezomib and MG132
      and TRAIL protein on two TRAIL-resistant human colon cancer cell lines, DLD1
      TRAIL/R and LOVO-TRAIL/R. Both bortezomib and MG132 in combination with TRAIL
      enhanced apoptotosis induction in these cells, as evidenced by enhanced cleavage
      of caspases 8, 9, and 3, Bid, poly(ADP-ribose) polymerase and by the release of
      cytochrome C and Smac. Subsequent studies showed that combined treatment with
      bortezomib or MG132 resulted in an increase of death receptor (DR) 5 and Bik at
      protein levels but had no effects on protein levels of DR4, Bax, Bak, Bcl-2, Bcl
      XL or Flice-inhibitory protein (FLIP). Moreover, c-Jun N-terminal kinase (JNK) is
      activated by these proteasome inhibitors. Blocking JNK activation with the JNK
      inhibitor SP600125 attenuated DR5 increase, but enhancement of apoptosis
      induction and increase of Bik protein were not affected. However, bortezomib
      mediated TRAIL sensitization was partially blocked by using siRNA to knockdown
      Bik. Thus, our data suggests that accumulation of Bik may be critical for
      proteasome inhibitor-mediated resensitization of TRAIL.

PMID- 16082183
TI  - Metastasis suppressor genes: from gene identification to protein function and
      regulation.
AB  - In the past decade, findings from various disciplines of research have stimulated
      a reevaluation of fundamental concepts of the biology of metastasis. The
      convergence of two avenues of research has largely been responsible for this
      shift. First, clinical and experimental studies of specific steps of the
      metastatic cascade have shown that cancer cells often disseminate early in the
      natural history of disease and can persist at secondary sites for extended
      periods of time. These findings suggest that disseminated cells remain subject to
      growth regulation at distant sites as "dormant" single cells or microscopic
      metastases consisting of small numbers of cells. Second, complementary
      functional, biochemical, and signal transduction studies have identified a
      specific class of proteins that suppress the formation of overt metastases. These
      proteins are encoded by metastasis suppressor genes, which are operationally
      defined as genes that suppress in vivo metastasis without inhibiting primary
      tumor growth when expressed ectopically in metastatic cell lines. While
      metastasis suppressor proteins may affect many steps in metastatic development,
      recent evidence specifically implicates several of these proteins in the
      regulation of growth of disseminated cells at secondary sites. This review
      describes the evolving understanding of rate-limiting steps of metastatic growth,
      and the role of metastasis suppressor proteins in the regulation of these
      processes. We will give an overview of the studies of metastasis suppressor
      protein function, which have shifted our attention toward mechanisms of growth
      control at the secondary site (i.e., "metastatic colonization"). Emphasis is
      placed upon the complimentary research in the fields of metastasis and signal
      transduction that has identified signaling pathways controlling metastatic
      colonization. We also discuss the regulation of metastasis suppressor proteins
      and the potential biological and biochemical mechanisms responsible for their
      organ-type specificity. Finally, the implication of these emerging concepts on
      the development of therapeutic strategies will be presented.

PMID- 16082184
TI  - Radiolabeling and biological evaluation of DOTA-Ph-Al derivative conjugated to
      anti-EGFR antibody ior egf/r3 for targeted tumor imaging and therapy.
AB  - An appropriate bifunctional chelating agent namely DOTA-Ph-Al was developed for
      the conjugation with biological vectors (anti EGFr antibody). We hereby report
      the synthesis of p-bromoacetamidobenzyl derivative of DOTA and its conjugation to
      monoclonal antibody anti-EGFR ior egf/r3. Immunoconjugate was prepared by
      conjugation of p-bromoacetamidobenzyl derivative of DOTA with ior egf/r3.
      Modified antibody was purified by size exclusion chromatography. DOTA-Ph-Al-ior
      egf/r3 exhibited quantitative 99mTc-labeling (>96%) with specific activity 10-20
      mCi/mg of protein and 90Y-labeling with specific activity 2-5 mCi/mg.
      Immunoreactivity was determined by flow cytometry. Receptor ligand assay on
      murine cell line EAT and human tumor cell line U-87MG showed Kd = 2.87 nM and
      4.86 nM respectively. The stability in serum indicated that 99mTc remained bound
      to antibodies up to 24h and 98% 90Y was associated with the mAb for five days.
      Biodistribution characteristics of Ab-conjugate radiolabeled to 99mTc and 90Y
      radionuclide was examined in BALB/c mice grafted with EAT and athymic mice with U
      87MG cell line demonstrated high tumor uptake with 5.5 +/- 1.3 and 7.85 +/-
      1.2%ID/g at four and 24 h for 99mTc- DOTA-Ph-AI-ior egf/r3 in EAT tumors after
      post injection respectively. Maximal radiotracer uptake peaked 17.6 +/- 2.5%ID/g
      in EAT tumor and 12.89 +/- 0.66% ID/g in U-87MG tumor at 48h for 90Y. The drug
      excreted through renal routes as the activity in the kidneys was 13.42 +/-
      0.33%ID/g at 1 h and 4.51 +/- 1.2%ID/g at 4 h for 99mTc- DOTA-Ph-Al-ior egf/r3.

PMID- 16082185
TI  - In vivo and in vitro inhibition of pancreatic cancer growth by targeted alpha
      therapy using 213Bi-CHX.A"-C595.
AB  - PURPOSE: The aim of this study was to investigate the effect of targeted alpha
      therapy for the control of in vitro pancreatic cancer cell clusters and
      micrometastatic cancer lesions in vivo. METHODS: The expression of tumor
      associated antigen MUC-1 on three pancreatic cancer cell clusters and animal
      xenografts was detected by indirect immmunostaining. Monoclonal antibodies C595
      (test) and A2 (non-specific control) were labeled with 213Bi using the chelator
      CHX.A" to form the alpha-immunoconjugate (AIC). Cell clusters were incubated with
      AIC and examined at 48 h. Apoptosis was documented using the TUNEL assay. In
      vivo, an antiproliferative effect for tumors was tested at two days post
      subcutaneous cell inoculation. Mice were injected with different concentrations
      of AIC by regional or systemic administration. Changes in tumor progression were
      assessed by tumor size. RESULTS: MUC-1 is strongly expressed on CFPAC-1, PANC-1
      and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The
      AICs can target and kill cancer cell clusters (100 mm) in vitro. Some 73-81 % of
      cells were TUNEL positive cells in the clusters after incubation with AIC. At two
      days post- cell inoculation in mice, a single local injection of 74 and 148
      MBq/kg of AIC causes complete inhibition of tumor growth. Systemic injections of
      111, 222 and 333 MBq/kg of AIC cause significant tumor growth delay after 16
      weeks, compared with the nonspecific control providing 333 MBq/kg after 16 weeks.
      CONCLUSIONS: CFPAC-1, PANC-1 and CAPAN-1 pancreatic cancer cell clusters and
      pancreatic tumor xenografts show high expression of the MUC-1 target antigen.
      213Bi-C595 can specifically target and regress pancreatic cancer cell clusters in
      vitro, and delay and inhibit tumor growth in vivo. 213Bi-C595 may be a useful
      agent for the treatment of micrometastatic pancreatic cancer with overexpression
      of MUC 1 antigen in post-surgical patients with minimal residual disease.

PMID- 16082186
TI  - RNA interference: a new therapeutic strategy of cancer.

PMID- 16082187
TI  - PE, a new sulfated saponin from sea cucumber, exhibits anti-angiogenic and anti
      tumor activities in vitro and in vivo.
AB  - Here, we examined the in vitro and in vivo anti-angiogenesis and anti-tumor
      activities of PE, a new marine-derived compound. Inhibition of angiogenesis was
      assessed in vitro using proliferation, migration, adhesion, tube-formation and
      apoptosis assays in PE-treated HMECs and HUVECs. In vivo, CAM assays were used to
      assess inhibition effect of PE on physiological angiogenesis, and
      immunofluorescent microscopy was used to examine tumor microvessel density and
      apoptosis in PE-treated mouse tumor models. Finally, Western blotting analyses
      were performed to examine the effect of PE on VEGF signaling in HMECs. The
      results showed that PE inhibited proliferation of HMECs and HUVECs with IC50
      values of 2.22 +/- 0.31 microM and 1.98 +/- 0.32 microM, induced endothelial cell
      apoptosis at concentrations <2 microM, induced dose-dependent suppression of cell
      migration, cell adhesion and tube formation in HMECs and HUVECs, and showed anti
      proliferative activities against several tumor cell lines (IC50 values of
      approximately 4 microM). In vivo, PE (5 nM/egg) suppressed spontaneous
      angiogenesis in our CAM assay, and induced marked growth inhibition in mouse
      sarcoma 180 and hepatoma 22 models. Specifically, PE treatment reduced mouse
      sarcoma 180 tumor volume by triggering apoptosis of both tumor and tumor
      associated endothelial cells, preferentially targeting on endothelial cells
      comparable with tumor cells. Finally, PE treatment suppressed the active
      (phosphorylated) forms of VEGFR2, Akt, ERK, FAK and paxillin, which are involved
      in endothelial cell survival, proliferation, adhesion and migration. Our results
      indicate that PE exerts an anti-angiogenic activity associated with inhibition of
      VEGFR2 signaling, and an anti-tumor activity associated with decreased
      proliferation of tumor cells and increased apoptosis of both endothelial cells
      and tumor cells.

PMID- 16082188
TI  - Psoriasin (S100A7) and calgranulin-B (S100A9) induction is dependent on reactive
      oxygen species and is downregulated by Bcl-2 and antioxidants.
AB  - S-100 proteins are calcium-binding proteins with important growth regulatory
      functions. Of these proteins, psoriasin and calgranulin-B have been shown to be
      highly upregulated in ductal carcinoma in situ (DCIS) of the breast and in
      psoriasis. The purpose of this study was to further elucidate the functional
      relevance of the overexpression of these two S-100 proteins in psoriasis and
      DCIS. We report the induction of both proteins by reactive oxygen species,
      phorbol ester TPA, and the induction of psoriasin in response to the PI3K
      inhibitor wortmannin. We also demonstrate that Bcl-2 overexpression represses the
      induction of psoriasin and calgranulin-B under these different conditions. The
      same effect was obtained with the antioxidant NAC, which indicates that the
      suppression of psoriasin and calgranulin-B induction is mediated by the
      antioxidant function of Bcl-2. Furthermore, we demonstrate that overexpression of
      a dominant negative IKKbeta also inhibits the induction of psoriasin suggesting
      that the NFkappaB pathway is involved in the induction of this protein. Also, we
      found NFkappaB responsive DNA elements in the upstream promoter region of
      psoriasin. MCF10A cells with a stable retroviral overexpression of psoriasin were
      significantly more resistant to H2O2-induced cell death than control cells
      further supporting the hypothesis that these S-100 proteins may play a role in
      oxidative stress response.

PMID- 16082189
TI  - Signal therapy of breast cancers by the HDAC inhibitor FK228 that blocks the
      activation of PAK1 and abrogates the tamoxifen-resistance.
AB  - PAK1, a Rac/CDC42-dependent Ser/Thr kinase, is required for both
      neurofibromatosis (NF) and RAS transformation in vivo. FK228, a histone
      deacetylase (HDAC) inhibitor, activates a very specific set of genes such as the
      tumor suppressor WAF1, an inhibitor of cyclin-dependent kinases (CDKs), and
      suppresses the growth of these tumors. In addition, this drug downregulates
      cyclin D1, which is upregulated by RAS through PAK1, in breast cancers. In this
      study, we demonstrate that FK228 at 0.1-1 nM significantly reduces the kinase
      activity of PAK1 in these cells, without affecting the protein level of PAK1.
      Interestingly, estrogen receptor (ER) and PAK1 mutually activate each other in
      breast cancers. Here we provide an evidence suggesting that breast cancers
      require PAK1 for their estrogen-dependent growth. Moreover, the treatment with
      FK228 strongly inhibits the estrogen-dependent growth of human breast cancers
      (both tamoxifen-sensitive and resistant cell lines) in vivo, suggesting that
      FK228 and other anti-PAK1 drugs would be useful for the treatment of breast
      cancers which become resistant to currently used estrogen antagonists such as
      tamoxifen.

PMID- 16082190
TI  - Preliminary investigation of the inhibitory effects of the tyroservaltide (YSV)
      tripeptide on human hepatocarcinoma BEL-7402.
AB  - This study aimed to investigate the inhibitory effect of tyroservaltide (YSV) on
      the human hepatocarcinoma BEL-7402 transplanted into nude mice and to explore its
      possible anti-tumor mechanism. Nude mice bearing xenografts of the human BEL-7402
      hepatoma were given daily i.p. injections of YSV or saline (as a control) after
      the tumor were transplanted. Calculating tumor volume and measuring tumor weight
      determined the extent of inhibition of xenografts. The ultrastructure of tumor
      cells was observed by electron microscopy. Proliferating cell nuclear antigen
      (PCNA) expression in tissues of the YSV-treated group was observed by
      immunohistochemistry. Apoptosis of tumor tissue cells was assayed by the terminal
      transferase uridyl nick end labeling (TUNEL) method. At doses of 80 microg/kg/d
      and 160 microg/kg/d, YSV could significantly inhibit growth of tumors
      transplanted into nude mice, with inhibition rates of 60% and 64%, respectively,
      compared with that of the controls (P < 0.05). Moreover, YSV changed the
      ultrastructure of tumor cells, resulting in necrosis and apoptosis of the tumor
      cells. Compared with the saline group, the expression of PCNA in tumor tissue
      decreased and the count of apoptotic cell increased. Therefore, YSV can
      significantly inhibit the growth of human hepatocarcinoma BEL-7402 in nude mice,
      decrease the expression of PCNA in tumor tissue, and induce tumor cell apoptosis.

PMID- 16082191
TI  - MAGED4-expression in renal cell carcinoma and identification of an HLA-A*25
      restricted MHC class I ligand from solid tumor tissue.
AB  - MAGE derived HLA ligands have repeatedly been shown to elicit T-cell responses
      against tumor cells. In renal cell carcinoma (RCC), however, only few T-cell
      epitopes from cancer testis antigens have been described. To identify potential
      candidates, we applied a combined approach of microarray/qPCR expression analysis
      and sequencing of HLA ligands from RCC by mass spectrometry. We analyzed the
      expression of 21 MAGE genes in ten RCC samples and two glioblastoma samples and
      could identify the first MHC class I ligand NIGDEALIGRW from MAGED4 presented by
      HLA-A*25 on RCC solid tumor tissue. MAGED4 was expressed in 30% of RCC and both
      glioblastoma samples. Among the other MAGE family members only MAGEB2 and -C1 and
      the broadly expressed MAGED1, -D2, -F1 and -H1 were expressed in RCC. Ligands
      from MAGED4 could thus be interesting tumor-associated antigens in a subset of
      RCC, even though the identified ligand is presented by a rather rare allele.

PMID- 16082192
TI  - Suppression of MUC1 synthesis downregulates expression of the epidermal growth
      factor receptor.
AB  - The transmembrane mucin, MUC1, is overexpressed on many human carcinoma cells,
      increasing their metastatic potential through decreased cell-cell and cell-matrix
      adhesion. These cellular changes are mediated both through the altered physical
      properties of the mucin itself and through the role of the MUC1 cytoplasmic
      domain as a signaling molecule. The epidermal growth factor receptor (EGFR) is
      also overexpressed in many cancers and both it and MUC1 constitute important
      therapeutic targets. In the present study, expression of MUC1 was downregulated
      by treatment of KB carcinoma cells with a MUC1 small interfering RNA resulting in
      an inhibition of cell proliferation and colony formation and an increase in cell
      cell aggregation. Surprisingly, suppression of MUC1 also inhibited expression of
      EGFR at both the mRNA and protein levels whereas the reciprocal effect was not
      observed. These results demonstrate a role for MUC1 in the regulation of EGFR
      expression and suggest that MUC1 gene silencing may represent a novel therapeutic
      approach in the treatment of a variety of human cancers.

PMID- 16082193
TI  - Molecular pathways in the chemosensitization of cisplatin by quercetin in human
      head and neck cancer.
AB  - The aim of this study was to develop novel and less toxic therapy for human head
      and neck squamous cell carcinoma (HNSCCs) and to investigate the mechanism of
      quercetin-induced apoptosis in human laryngeal HeP2 cells and its effect on
      cisplatin induced apoptosis. Priming the cells with quercetin (40 microM)
      increased the apoptosis induced by cisplatin alone from 18.7% to 42.2% in HeP2
      cells. Quercetin induced apoptosis via inhibition of Akt/PKB phosphorylation, an
      upstream kinase of pro-survival protein kinase cascade. Inhibition of Akt
      phosphorylation was coupled with a significant decrease of anti-apoptotic Bcl-2
      and Bcl-XL. Quercetin caused a downregulation of Cu-Zn Superoxide Dismutase which
      perhaps led to an increase of reactive oxidative stress (ROS). The decrease of
      Bcl-2 and Bcl-XL along with this oxidative stress caused release of mitochondrial
      cytochrome c into the cytosol and subsequent induction of pro-caspase-9
      processing. Inhibition of heat shock proteins may be another mechanism for the
      pro-apoptotic activity of quercetin. Cisplatin induced apoptosis appears to be
      partly due to induction of JNK activity which leads to the activation of
      endonucleases. Increased JNK activity led to increased phosphorylation of c-Fos.
      Cisplatin additionally appears to induce apoptosis by down-regulating the enzyme
      Nitric Oxide Synthase (NOS). Cisplatin also acts by increasing pro-apoptotic Bax
      concentration in the cells thereby leading to caspase-9 activation via the
      mitochondrial pathway. These results support the fact that quercetin and
      cisplatin act by separate pathways and demonstrate interactions between the
      pathways that result in synergistic actions. Possibly of greater potential value
      is the interaction of a conventional cytotoxic drug (cisplatin) and a nontoxic
      chemopreventive agent (quercetin) thereby allowing the use of less toxic doses of
      chemotherapy for treatment of HNSCCs.

PMID- 16082194
TI  - Targeting of c-Met and urokinase expressing human glioma cell lines by retrovirus
      vector displaying single-chain variable fragment antibody.
AB  - Amphotropic retroviruses with modified envelope displaying single-chain antibody
      fragment (scFv) directed against the c-Met receptor were recently generated and
      found to efficiently and selectively deliver genes into hepatocarcinoma cells. A
      large proportion of human gliomas also frequently overexpresses c-Met. We
      therefore explored the possibility of infecting glioma cells using such
      retroviruses bearing an scFv directed against c-Met. In one construct, a
      urokinase (uPA) cleavage site was inserted between the scFv and the envelope. We
      assessed the transduction by these chimeric viruses of a panel of seven human
      glioma cell lines that we characterized for their c-Met and uPA levels. We found
      that abundance of the c-Met receptor and viral infection were inversely
      correlated if we used the retrovirus displaying scFv directed against c-Met,
      suggesting that the chimeric virus binds preferentially to the c-Met receptor,
      resulting in virus sequestration. Addition of the uPA site between the scFv
      moiety and the envelope restored the infectivity of the virus, consistent with a
      "two-step" infection process: (1) virus binding to the c-Met receptor, (2)
      cleavage of the scFv moiety by uPA, enabling the virus to dissociate from c-Met
      and entry into the cells via the Pit-2 receptor. Our study has significant
      implications for the design of targeting strategies for gliomas expressing high
      levels of c-Met.

PMID- 16082195
TI  - Downregulation of survivin by RNAi inhibits the growth of esophageal carcinoma
      cells.
AB  - Esophageal squamous cell carcinoma ranks among one of the most frequent cause of
      cancer death in the world. Understanding of the molecular mechanisms involved in
      the pathogenesis of esophageal cancer becomes critical to develop more effective
      treatments. Elevated expression of survivin in esophageal carcinoma has been
      reported before and suppression of survivin expression leads to many tumor cells
      growth inhibition. We hypothesized that downregulation of survivin would inhibit
      the growth of human esophageal cancer cells. RNA interference directed against
      survivin was introduced into a human esophageal squamous cell carcinoma cell line
      KYSE510. Stable clones were selected and western blot analysis was performed to
      detect the protein level of survivin. Tumor cell growth in vitro and in vivo was
      assessed by trypan blue exclusion and nude mice experiments. Annexin V/propidium
      iodide staining followed by flow cytometric analysis and TUNEL assay were used to
      detect apoptosis in cell culture and in nude mice. We found that RNA interference
      could efficiently and stably suppress survivin expression in KYSE510 cells.
      Downregulation of survivin resulted in significantly inhibition of tumor growth
      in vitro and in vivo. The mechanism appears to be increased induction of
      apoptosis. Our results suggest a potential role for the targeting of survivin in
      the treatments of esophageal carcinoma.

PMID- 16082196
TI  - Modulation of drug cytotoxicity by Iressa (ZD1839) in pancreatic cancer cell
      lines.
AB  - High expression of the epidermal growth factor receptor (EGFR) family confers a
      growth advantage on malignant cells in various tumor types. Most pancreatic
      cancers express EGFR, which seems to play an important role in the acquisition of
      aggressive clinical behaviour and in tumor invasion. Iressa (ZD1839), a
      quinazoline tyrosine kinase inhibitor selective for the EGF receptor, has shown
      good anti-tumor activity in both preclinical and clinical studies. Using two
      pancreatic cancer cell lines that express different EGFR and ErbB-2 levels, we
      analyzed the activity of Iressa and evaluated its modulation effect on four
      conventional cytotoxic drugs: gemcitabine, oxaliplatin, docetaxel and SN38.
      Iressa was tested at scalar doses up to the plasma peak level concentration and
      showed a similar weak cytostatic effect in both cell lines. Conversely, an
      additive or weak synergistic effect was observed when the drug was administered
      simultaneously with or following cytotoxic drugs. Our data show that Iressa has
      only a weak activity at doses within the plasmatic peak concentration and that
      its effect is independent of EGFR and p42/p44 expression and phosphorylation
      levels. This is in agreement with recent literature data that attribute an
      essential role to a specific EGFR mutation in mediating response to Iressa. This
      mutation was absent in both pancreatic cell lines tested.

PMID- 16082197
TI  - p53 proteasomal degradation: poly-ubiquitination is not the whole story.
AB  - Protein degradation is a key cellular process involved in almost every aspect of
      the living cell. The current prevailing concept is that proteins are stable
      unless marked by poly-ubiquitination for degradation by the proteasomes. Studies
      on the tumor suppressor p53 have indeed demonstrated that poly-ubiquitination of
      p53 by different E3 ubiquin ligases targets p53 for degradation by the 26S
      proteasomes. Recent findings suggest that p53 also undergoes ubiquitin
      independent degradation by the 20S proteasomes and that this process is regulated
      by NAD(P)H quinone oxidoreductase 1 (NQO1) together with NADH. This "degradation
      by default" mechanism sheds new light on our understanding of p53 degradation and
      possibly on protein degradation in general and may establish a new principle in
      protein stability with wide physiological implications.

PMID- 16082198
TI  - p21WAF1/CIP1 regulates the p300 sumoylation motif CRD1 through a C-terminal
      domain independently of cyclin/CDK binding.
AB  - Although best known for its ability to inhibit Cyclin/Cdk complexes and the
      replication protein PCNA, p21(WAF1/CIP1) is a multifunctional protein that
      interacts with many cellular binding partners, including a number of
      transcriptional regulators. Previously, we characterized p21 derepression of the
      p300 sumoylation-dependent transcriptional repression domain, CRD1. Such
      repression domains are at least partially dependent upon recruitment of histone
      deacetylase (HDAC) complexes but the mechanism through which p21 selectively
      disrupts CRD1 activity remains unknown. Here, we demonstrate that distinct motifs
      in the C-terminus of p21 are required for regulation of p300 CRD1 function and
      that this effect does not correlate with Cyclin or PCNA binding. Through the
      creation of N-terminal glutathione-s-transferase fusion proteins, which also
      overcome the problems of instability that result from many p21 mutations, we
      investigated p21 binding to HDACs. Although p21 binds both Class I and Class II
      HDACs in vitro, only weak association with HDAC1 and 2 is seen in cells. Mutation
      of the p21 PCNA binding domain significantly increases this interaction
      suggesting that binding is mutually exclusive and only naturally occurs under
      certain conditions. Binding of HDACs also failed to correlate with CRD1
      inducibility, suggesting that p21 targets other transcriptional repression
      complexes to mediate this effect.

PMID- 16082199
TI  - Mitotic instability in cancer: is there method in the madness?
AB  - It has been known for more than a century that neoplastic cells often exhibit
      disturbances of the mitotic process, but the causes have only recently been
      thoroughly explored. In many cancers, a combination of cell cycle checkpoint
      deficiency and abnormal shortening of telomeres predisposes to unbalanced
      chromosome segregation at cell division and the development of complex genomic
      rearrangements. Shortening of telomeric repeats beyond normal limits leads to
      fusion of chromosome ends and the formation of chromatin bridges at anaphase. In
      turn, these bridges may trigger at least three types of chromosomes mutation: (1)
      structural rearrangements of chromosomes through extensive chromatin
      fragmentation beyond the centromeric sequences, typically leading to the
      formation of isochromosomes and whole-arm translocations, (2) loss of whole
      chromosomes through mechanical detachment from the mitotic spindle machinery, and
      (3) failure of cytokinesis, leading to polyploidisation and supernumerary
      centrosomes, which may in turn orchestrate multipolar spindle configurations at a
      subsequent mitosis. Anaphase bridging rarely hinders further survival of tumor
      daughter cells. In contrast, multipolar mitoses may lead to extensive reshuffling
      of chromosome copies that compromise further clonal expansion. The telomere
      dependent instability can be partly counteracted by expression of telomerase
      during tumor progression, but genomic stabilisation is rarely, if ever, complete.

PMID- 16082200
TI  - A novel Cdk2 interactor is phosphorylated by Cdc7 and associates with components
      of the replication complexes.
AB  - Initiation of DNA replication in eukaryotic cells depends on the assembly of the
      prereplication complexes containing two hexamers, the Origin Recognition Complex
      (ORC) and the Minichromosome maintenance/DNA Replication Licensing complex (MCM);
      and on the subsequent conformational changes in the MCM complex leading to the
      formation of a competent DNA replication complex, firing of the DNA polymerase
      and disassembly of the MCM. The dynamics of the MCM complex is under the control
      of two Ser/Thr kinases, the Cell cycle-dependent kinase 2 (Cdk2) and Cell
      division cycle gene 7 (Cdc7). The precise substrates of the kinases at the
      origins and the sequence of events leading to the origins firing are not well
      understood. Using the two hybrid selection in yeast, we have identified a novel
      gene, the Cdk2 interacting protein, CINP. We show that CINP is a component of the
      active cyclin E /Cdk2 and cyclin A /Cdk2 complexes. CINP also interacts with Cdc7
      and is phopshorylated by Cdc7, but not by Cdk2. We further show that CINP binds
      to chromatin in a replication-dependent manner, and associates with ORC2
      containing complexes and MCM. We propose that CINP is part of the Cdc7-dependent
      mechanism of origin firing and a functional and physical link between Cdk2 and
      Cdc7 complexes at the origins.

PMID- 16082201
TI  - Gerry Melino.

PMID- 16082202
TI  - Developmental patterning in the wrong context: the paradox of epithelial ovarian
      cancers.
AB  - In contrast to many other types of cancer, epithelial ovarian cancers often
      exhibit differentiation patterns that are more specialized than those of the
      tissue of origin. Many epithelial ovarian cancers assume morphologic features
      reminiscent of the mullerian duct-derived epithelia, but are thought to arise
      from cells of the simple ovarian surface epithelium that is not of mullerian duct
      origin. This article discusses recent studies that implicate aberrant activation
      of embryonic pathways in ovarian cancer histogenesis, and highlights the intimate
      relationship between developmental plasticity and neoplasia.

PMID- 16082203
TI  - Stroma: tumor agonist or antagonist.
AB  - Extensive research has been conducted over several decades understanding the
      genetic changes that occur in normal cells to promote them towards a transformed
      state. However, it is becoming increasingly apparent that carcinoma growth
      requires more complex interactions for development and progression. Since tissue
      epithelium is composed of highly specialized cells that orchestrate specific
      activities, their proper development and function is highly dependent on
      contextual signals from the stroma. As such, it is conceivable that carcinoma
      development should also parallel these needs. In light of our recent evidence
      combined with established work demonstrating the role of the tissue stromal
      environment in cancer development, it is evident that tissue stroma exhibits
      context specific tumor suppressive and tumor-promoting abilities that serve to
      regulate dysfunction and neoplastic growth of the epithelium.

PMID- 16082204
TI  - Rb and LEK1: a "pas de deux" in cardiogenesis.
AB  - Cardiogenesis results from activation of a complex transcriptional network. The
      transcription factors work in a combinatorial manner to transactivate expression
      of constitutive genes. Embryonic stem (ES) cells are capable to recapitulate the
      early stages of cardiac cell differentiation. So far only the Bone Morphogenetic
      Protein (BMP)-dependent pathway switching on expression of Nkx2.5, one of the
      earliest cardiac transcription factor, has been described as the canonical
      cardiogenic pathway. Recently, using Rb-/- and LEK1-downregulated ES cells, we
      described a novel BMP-independent cardiogenic pathway implicating both Rb and
      LEK1, a mammalian homolog of the chicken cardiomyogenic factor 1(CMF1). Here, I
      discuss the role of Rb pathways in cell differentiation and the potential
      mechanisms underlying the effect of Rb/LEK1 interaction on cardiac specification
      of stem cells.

PMID- 16082205
TI  - Sororin, the cell cycle and sister chromatid cohesion.
AB  - Sister chromatid cohesion is essential for the maintenance of genome integrity.
      Errors in regulation of cohesion result in increased sensitivity to DNA damage,
      mis-segregation of chromosomes, and loss of genetic information. We recently
      showed that sororin is an essential regulator of sister chromatid cohesion in
      vertebrates. Interestingly, we identified sororin in a screen for proteins whose
      levels are controlled by the Anaphase Promoting Complex (APC), a cell cycle
      regulated ubiquitin ligase. Ubiquitination by the APC and the resulting
      degradation ensure that sororin levels are low throughout G1 and only rise during
      S phase. We speculate that this regulation is an essential part of the mechanism
      that ensures that cohesion is established only after there are in fact two sister
      chromatids to tie together. Cohesion thus established can then be used both to
      mediate recombinational DNA repair, as well as to ensure accurate sister
      chromatid segregation in anaphase. Both of these roles are essential to genome
      stability.

PMID- 16082206
TI  - Functional diversity in the gene network controlled by the master regulator p53
      in humans.
AB  - Individual differences in susceptibility to exposure induced diseases are likely
      due to variation in the DNA sequences of "environmental response" genes, many of
      which are arranged in complex regulatory networks. Among approximately 10 million
      inherited DNA variations, called single nucleotide polymorphisms (SNPs), perhaps
      only a few thousand, will actually influence human disease risk. We have combined
      bioinformatics and laboratory approaches to investigate genetic variation within
      the p53 stress response network. p53, a prominent tumor suppressor protein, is a
      master regulator that targets over a hundred genes for transcriptional
      upregulation or repression through sequence-specific interactions with DNA
      response elements (REs). We identified many human genes in the network that
      contain SNPs in REs that can be transactivated by p53. The discovery of these
      individual differences has implications for variation in human responses to
      environmental stresses, risk of disease, and responsiveness to drug therapies.
      The findings also provide insight into the evolution of complex networks and the
      role of master regulatory genes, such as p53, in such networks.

PMID- 16082207
TI  - The first 30 minutes in the life of a virus: unREST in the nucleus.
AB  - On entry of viral DNA into cells, a competition ensues between cellular factors
      that silence viral genes and transcriptional factors that block silencing and
      transcribe the DNA. In the case of herpes simplex virus 1, the first set of genes
      expressed after infection-are induced by a viral protein (alphaTIF or VP16).
      Expression of later (beta,gamma) genes in cells infected at low ratios of virus
      per cells requires a transcriptional activator (ICP4) that cannot block silencing
      and a protein, ICP0, hitherto characterized as a promiscuous transactivator.
      Recent studies indicate that ICP0 blocks silencing of viral DNA by dissociating
      HDACs 1 and 2 from the CoREST/REST repressor complex. HDACs 1/2 are
      phosphorylated and translocated to the nucleus. The findings have broad
      implications regarding silencing of the viral genome during latency and,
      potentially, the expression of genes encoded by other DNA viruses as well.

PMID- 16082208
TI  - Re-evaluating the role of Frat in Wnt-signal transduction.
AB  - Frat proteins are potent activators of canonical Wnt-signal transduction. By
      binding to GSK3, Frat prevents the phosphorylation and concomitant degradation of
      beta-catenin and allows the activation of downstream target genes by beta
      catenin/TCF complexes. The identification of the Xenopus Frat homologue GBP as an
      essential component of the maternal Wnt-pathway during embryonic axis formation
      suggested that Frat might fulfill a similar role in higher vertebrates. As a
      result most, if not all, studies addressing Frat function have focused on its
      ability to bind GSK3 and induce signaling through beta-catenin/TCF. Consequently,
      Frat has been advocated as the "missing link" that bridged signaling from
      Dishevelled to GSK3 in the canonical Wnt-pathway. Recent mouse-knockout studies
      however, call for a reevaluation of the physiological role of Frat. Mice that
      lack all Frat-family members appear to be normal and display no obvious defects
      in beta-catenin/TCF signaling. This observation reopens the question as to how
      GSK3 activity is controlled in vertebrate canonical Wnt-signal transduction in
      view of the apparent dispensability of Frat. Here we will review the studies that
      have been conducted on Frat proteins to date, with a specific focus on those that
      implicate a role for Frat in Wnt-signal transduction. In addition, we will
      discuss potential alternatives for the endogenous function of Frat.

PMID- 16082209
TI  - ATP-dependent chromatin remodeling and DNA double-strand break repair.
AB  - The repair of DNA double-strand breaks (DSBs) is critical for the maintenance of
      genomic stability. Two pathways for the repair of DBSs, nonhomologous end-joining
      (NHEJ) and homologous recombination (HR), have evolved in eukaryotes. These
      pathways, like processes such as transcription and replication, act on DNA that
      is embedded in nucleosomes. Recent studies have shown that DNA repair, like
      transcription, is facilitated both by histone tail modification and by ATP
      dependent chromatin remodeling. This review emphasizes recent reports that
      demonstrate a function for the ATP-dependent chromatin remodeling complexes INO80
      and RSC in NHEJ and HR. We also discuss the possible role of SWR1- and TIP60
      mediated nucleosomal histone exchange in DNA repair.

PMID- 16082210
TI  - Histone acetylation, chromatin remodelling and nucleotide excision repair: hint
      from the study on MFA2 in Saccharomyces cerevisiae.
AB  - Nucleotide excision repair (NER) is a sophisticated repair pathway that the cell
      utilizes to remove a broad range of DNA damage to help maintain the functional
      integrity of the genome. In the context of DNA packaged into chromosomes it is
      clear that the NER machinery does not repair all regions with equal efficiency.
      Recently, we found after UV that histone acetylation and chromatin remodelling
      were activated. UV irradiation triggers genome-wide histone hyperacetylation at
      both histone H3 and H4. However, in nucleosomes at the repressed MFA2 promoter
      only histone H3, but not histone H4, is hyperacetylated following UV. This Gcn5p
      mediated histone H3 hyperacetylation enables efficient NER at MFA2. Chromatin in
      this promoter also becomes more accessible after UV. This is not dependent on
      Gcn5p, yet it is partially dependent on Swi2p. In later repair times both events
      gradually return to the pre-UV state. The post-UV histone modifications and
      chromatin remodelling at the repressed MFA2 promoter do not activate MFA2
      transcription, nor do they require damage recognition by Rad4p or Rad14p. These
      experiments indicate early events are triggered in chromatin in response to UV
      treatment, and they are likely needed for efficient NER.

PMID- 16082211
TI  - Molecular targets and anticancer potential of indole-3-carbinol and its
      derivatives.
AB  - Indole-3-carbinol (I3C) is produced by members of the family Cruciferae, and
      particularly members of the genus Brassica (e.g., cabbage, radishes, cauliflower,
      broccoli, Brussels sprouts, and daikon). Under acidic conditions, 13C is
      converted to a series of oligomeric products (among which 3,3'-diindolylmethane
      is a major component) thought to be responsible for its biological effects in
      vivo. In vitro, 13C has been shown to suppress the proliferation of various tumor
      cells including breast cancer, prostate cancer, endometrial cancer, colon cancer,
      and leukemic cells; induce G1/S arrest of the cell cycle, and induce apoptosis.
      The cell cycle arrest involves downregulation of cyclin D1, cyclin E, cyclin-
      dependent kinase (CDK)2, CDK4, and CDK6 and upregulation of p15, p21, and p27.
      Apoptosis by I3C involves downregulation antiapoptotic gene products, including
      Bcl-2, Bcl-xL, survivin, inhibitor-of-apoptosis protein (IAP), X chromosome
      linked IAP (XIAP), and Fas-associated death domain protein-like interleukin-1
      beta-converting enzyme inhibitory protein (FLIP); upregulation of proapoptotic
      protein Bax; release of micochondrial cytochrome C; and activation of caspase-9
      and caspase-3. This agent inhibits the activation of various transcription
      factors including nuclear factor-kappaB, SP1, estrogen receptor, androgen
      receptor and nuclear factor-E2-related factor 2 (Nrf2). This indole potentiates
      the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      through induction of death receptors and synergises with chemotherapeutic agents
      through downregulation of P-glycoprotein (P-gp). In vivo, I3C was found to be a
      potent chemopreventive agent for hormonal-dependent cancers such as breast and
      cervical cancer. These effects are mediated through its ability to induce
      apoptosis, inhibit DNA-carcinogen adduct formation, and suppress free-radical
      production, stimulate 2-hydroxylation of estradiol, inhibit invasion and
      angiogenesis. Numerous studies have indicated that I3C also has a strong
      hepatoprotective activity against various carcinogens. Initial clinical trials in
      women have shown that I3C is a promising agent against breast and cervical
      cancers.

PMID- 16082212
TI  - Ran-GTP regulates kinetochore attachment in somatic cells.
AB  - The Ran GTPase controls multiple mitotic processes in Xenopus egg extracts,
      including mitotic checkpoints, spindle assembly and post-mitotic nuclear envelope
      reassembly. We have analyzed Ran's role in somatic cells. We uncovered a novel
      mitotic role of Ran-GTP, involving the Crm1 nuclear export receptor. This pathway
      is an important mode of Ran-GTP function during mitosis in mammalian somatic
      cells, which mediates the recruitment of the RanGAP1/RanBP2 complex to
      kinetochores and maintains the microtubule-based fibers connecting kinetochores
      to spindle poles (k-fibers). Here we discuss potential implications of these
      findings for normal k-fiber assembly.

PMID- 16082213
TI  - CDC25B phosphorylation by Aurora-A occurs at the G2/M transition and is inhibited
      by DNA damage.
AB  - CDC25B is one of the three human dual-specificity phosphatases involved in the
      activation of cyclin-dependent kinases at key stages of the cell division cycle.
      CDC25B that is responsible for the activation of CDK1-cyclin B1 is regulated by
      phosphorylation. The STK15/Aurora-A kinase locally phosphorylates CDC25B on
      serine 353 at the centrosome during the G2/M transition. Here we have
      investigated this phosphorylation event during the cell cycle, and in response to
      activation of the G2 DNA damage checkpoint. We show that accumulation of the S353
      phosphorylated form of CDC25B at the centrosome correlates with the
      relocalization of cyclin B1 to the nucleus and the activation of CDK1 at entry
      into mitosis. Upon activation of the G2/M checkpoint by DNA damage, we
      demonstrate that Aurora-A is not activated and consequently CDC25B is not
      phosphorylated. We show that ectopic expression of Aurora-A results in a bypass
      of the checkpoint that was partially overcome by a S353A mutant of CDC25B.
      Finally, we show that bypass of the G2/M checkpoint by the CHK1 kinase inhibitor
      UCN-01 results in the activation of Aurora-A and phosphorylation of CDC25B on
      S353. These results strongly suggest that Aurora-A-mediated phosphorylation of
      CDC25B at the centrosome is an important step contributing to the earliest events
      inducing mitosis, upstream of CDK1-cyclin B1 activation.

PMID- 16082214
TI  - Role of the cell cycle in the pathobiology of central nervous system trauma.
AB  - Upregulation of cell cycle proteins occurs in both mitotic and post-mitotic
      neural cells after central nervous system (CNS) injury in adult animals. In
      mitotic cells, such as astroglia and microglia, they induce proliferation,
      whereas in post-mitotic cells such as neurons they initiate caspase-related
      apoptosis. We recently reported that early central administration of the cell
      cycle inhibitor flavopiridol after experimental traumatic brain injury (TBI)
      significantly reduced lesion volume, scar formation and neuronal cell death,
      while promoting near complete behavioral recovery. Here we show that in primary
      neuronal or astrocyte cultures structurally different cell cycle inhibitors
      (flavopiridol, roscovitine, and olomoucine) significantly reduce upregulation of
      cell cycle proteins, attenuate neuronal cell death induced by etoposide, and
      decrease astrocyte proliferation. Flavopiridol, in a concentration dependent
      manner, also attenuates proliferation/activation of microglia. In addition, we
      demonstrate that central administration of flavopiridol improves functional
      outcome in dose-dependent manner after fluid percussion induced brain injury in
      rats. Moreover, delayed systemic administration of flavopiridol significantly
      reduces brain lesion volume and edema development after TBI. These data provide
      further support for the therapeutic potential of cell cycle inhibitors for the
      treatment of clinical CNS injury and that protective mechanisms likely include
      reduction of neuronal cell death, inhibition of glial proliferation and
      attenuation of microglial activation.

PMID- 16082215
TI  - DNA replication initiates at different sites in early and late S phase within
      human ribosomal RNA genes.
AB  - Metazoan replication origins often contain multiple potential initiation sites,
      and the selection of which of the potential sites are used appears to be
      dependent upon multiple factors, including the state of differentiation, cell
      metabolism, and local transcriptional activity. Numerous studies have shown that
      a replication origin exists within the non-transcribed spacer region of the human
      ribosomal RNA gene. We here analyze nascent leading strand DNA from S phase human
      lymphoid cells, and find that while the majority of rDNA replicates in mid- and
      late S phase and preferentially initiates replication 6 kbp from the
      transcription start site, in very early S phase the preferred initiation site is
      much closer to the transcription start site and may involve rDNA promoter
      sequences. This early site is coincident with a minimum GC skew value, diagnostic
      for replication origins in bacteria and yeast. These results suggest that
      replication timing can influence initiation site selection. The timing and
      nucleolar localization of rDNA further suggest that this site likely participates
      in the small number of perinucleolar initiation foci observed in very early S
      phase cells that represent the beginning of cellular DNA replication.

PMID- 16082216
TI  - Death-from-cancer signatures and stem cell contribution to metastatic cancer.
AB  - Genome-wide expression profiling studies reveal a transcriptionally distinct sub
      type of human solid tumors with a marked propensity toward metastatic
      dissemination, highly malignant clinical behavior, and poor therapy outcome in
      cancer patients diagnosed with the early stage carcinomas of various origins.
      This sub-set of tumors acquires full metastatic potential, including an emergence
      and seeding of potent metastasis precursor cells, early in tumor progression.
      Collectively, these data suggest an early involvement in development of this
      transcriptionally defined sub-type of human carcinomas of a highly malignant
      combination of mutant alleles conferring the proclivity to metastasize and/or an
      engagement in transformation and tumor progression of stem cells and/or early
      progenitor cells. Enrichment of primary tumors with normal stem cells increases
      the likelihood of horizontal genomic transfer (large-scale transfer of DNA and
      chromatin) between stem cells and cancer cells via cell fusion and/or uptake of
      apoptotic bodies and generation of reprogrammed somatic cell hybrids with self
      renewing highly malignant phenotype.

PMID- 16082217
TI  - The intracellular tyrosine kinase Brk sensitizes non-transformed cells to
      inducers of apoptosis.
AB  - The intracellular tyrosine kinase Brk is expressed in regenerating epithelial
      tissues with highest levels in the gastrointestinal tract and skin. In these
      tissues, Brk is restricted to epithelial cells that are exiting the cell cycle
      and undergoing terminal differentiation. While not expressed in mammary gland,
      Brk expression is often induced in primary breast tumors and breast tumor cell
      lines. To identify potential oncogenic functions of Brk, we utilized the
      immortalized Rat1a rat fibroblast cell line that is highly sensitive to
      transformation. We generated Rat1a cell lines that stably overexpress wild-type
      and activated Brk, and we analyzed their growth properties and ability to undergo
      apoptosis in response to stress and DNA damage. Overexpression of Brk did not
      induce anchorage-independent growth, and no changes in cell morphology or cell
      cycle progression were observed. However, when constitutively expressed, Brk
      sensitized Rat1a cells to a variety of apoptotic stimuli including serum
      deprivation and a combination of UV irradiation and serum starvation. These
      findings indicate that Brk does not promote proliferation of non-transformed
      cells, but plays a positive role in the regulation of the apoptotic response to
      DNA-damage and stress.

PMID- 16082218
TI  - New and old functions of STAT3: a pivotal target for individualized treatment of
      cancer.
AB  - Signal transducers and activators of transcription (STAT) regulate a plethora of
      cytokine responses. Recently, aberrant signaling by STAT proteins has been
      demonstrated to play important roles in the pathogenesis of many neoplasms, by
      promoting cell cycle progression and survival, stimulating angiogenesis, and
      impairing immunological responses and tumor surveillance. We have developed
      genetic tools to evaluate STAT-dependent malignancy and showed that survival and
      growth of lymphoid malignancies requires expression of STAT3. In contrast, loss
      of STAT3 in normal cells does not impair their growth or survival; but in spite
      of this apparent dispensability of STAT3, STAT3-null fibroblasts are resistant to
      transformation by a variety of oncogenes. The precise molecular mechanisms
      responsible for the tumorigenic activity of STAT3 have been only partially
      elucidated. While the tyrosine phosphorylation of STAT3, which is indicative of
      its signal-dependent activation, is a common occurrence in tumors, and appears to
      play a crucial role in some malignancies, a variety of new data suggest that it
      can be dispensable under some circumstances and STAT3 can participate in
      transformation through novel and non-canonical mechanisms. The discovery and
      dissection of non-canonical modes of STAT3 action will open new avenues for the
      design of effective therapeutics capable of neutralizing the tumorigenic
      properties of this molecule.

PMID- 16082219
TI  - Repair of double-strand DNA breaks by the human nonhomologous DNA end joining
      pathway: the iterative processing model.
AB  - Naturally-occurring ionizing radiation and reactive oxygen species (ROS) from
      oxidative metabolism are factors that have challenged all life forms during the
      course of evolution. Ionizing radiation (IR) and reactive oxygen species cause a
      diverse set of double-strand DNA end configurations. Non-homologous DNA end
      joining (NHEJ) is an optimal DNA repair pathway for dealing with such a diverse
      set of DNA lesions. NHEJ can carry out nucleolytic, polymerization, and ligation
      operations on each strand independently. This iterative processing nature of NHEJ
      is ideal for repair of pathologic and physiologic double-strand breaks because it
      permits sequential action of the NHEJ enzymes on each DNA end and on each strand.
      The versatility of the Artemis:DNA-PKcs endonuclease in cleaving 5' and 3'
      overhangs, hairpins, gaps, flaps, and various loop conformations makes it well
      suited for DNA end modifications on oxidized overhangs. In addition, the ability
      to cleave stem-loop and hairpin structures permits it to open terminal fold-back
      configurations that may arise at DNA ends after IR damage. The ability of the
      XRCC4:DNA ligase IV complex to ligate one strand without ligation of the other
      permits additional end joining flexibility in NHEJ and raises the possibility of
      optional involvement of repair proteins from other pathways.

PMID- 16082220
TI  - Search for testicular cancer gene hits dead-end.
AB  - Testicular germ cell tumors (TGCTs) are the first tumors where the cell of
      origin, and the time of transformation were precisely defined. TGCTs in mice
      originate from primordial germ cells (PGCs) and develop within the testis during
      fetal development. TGCTs occur at an appreciable frequency (5%) only in the 129
      family of inbred strains of laboratory mice, suggesting strong genetic control.
      These developmental and genetic properties make the 129 strains an exceptional
      model system to dissect TGCT pathogenesis. Ter is one of the most potent cancer
      modifiers genes known; it is a single gene mutation that causes progressive loss
      of PGCs on all inbred strain backgrounds and dramatically increased
      susceptibility to spontaneous TGCTs only on the 129 background. We recently
      showed that inactivation of the Dead end gene causes the Ter phenotype. Sequence
      analysis of Dead end encoded protein indicates it is homologous to factors
      involved in gene editing. The identity of Ter as Dead end and its function in
      PGCs will help clarify the role of editing in PGC biology and elucidate the
      causes of TGCTs in mice and humans.

PMID- 16082221
TI  - ATM-mediated phosphorylations inhibit Mdmx/Mdm2 stabilization by HAUSP in favor
      of p53 activation.
AB  - The p53 tumor suppressor protein has a major role in protecting genome integrity.
      Under normal circumstances Mdmx and Mdm2 control the activity of p53. Both
      proteins inhibit the transcriptional regulation by p53, while Mdm2 also functions
      as an E3 ubiquitin ligase to target both p53 and Mdmx for proteasomal
      degradation. HAUSP counteracts the destabilizing effect of Mdm2 by direct
      deubiquitination of p53. Subsequently, HAUSP was shown to deubiquitinate Mdm2 and
      Mdmx, thereby stabilizing these proteins. The ATM protein kinase is a key
      regulator of the p53 pathway in response to double strand breaks (DSBs) in the
      DNA. ATM fine-tunes p53's response to DNA damage by directly phosphorylating it,
      by regulating additional post-translational modifications of this protein, and by
      affecting two p53 regulators: Mdm2 and Mdmx. ATM directly and indirectly induces
      Mdm2 and Mdmx phosphorylation, resulting in decreased activity and stability of
      these proteins. We recently provided a mechanism for the reduced stability of
      Mdm2 and Mdmx by showing that ATM-dependent phosphorylation lowers their affinity
      for the deubiquitinating enzyme HAUSP. Altogether, the emerging picture portrays
      an elaborate, but fine-tuned, ATM-mediated control of p53 activation and
      stabilization following DNA damage. Further insight into the mechanism by which
      ATM switches the interactions between HAUSP, Mdmx, Mdm2 and p53, to favor p53
      activation may offer new tools for therapeutic intervention in the p53 pathway
      for cancer treatment.

PMID- 16082222
TI  - Hedgehogs as negative regulators of the cell cycle.
AB  - During the development of multicellular animals, cell proliferation must be
      precisely controlled, as deregulated proliferation can lead to overgrowth and
      cancer. In addition, proliferation must be tightly integrated with pattern
      formation and differentiation to generate the required number of cells in the
      right organs, and at the right time. All major signaling pathways employed during
      embryogenesis have been implicated in cell cycle regulation, indicating that no
      single pathway has been dedicated to this task. Also, the precise role of a
      particular signaling pathway in regulating proliferation is highly dependent on
      the cellular context, and may have opposite effects on cell cycle progression in
      different cells and tissues. The Hedgehog (Hh) family of signaling proteins is
      known to control both differentiation and proliferation during development. So
      far, studies addressing the effect of Hh signaling on proliferation have shown it
      to have a stimulatory effect on cell cycle progression. Here we review several
      recent studies indicating that Hh signaling can also have the opposite effect,
      directing cell cycle exit in a number of cell types in vertebrate and in
      invertebrate embryos.

PMID- 16082223
TI  - APOBEC4, a new member of the AID/APOBEC family of polynucleotide (deoxy)cytidine
      deaminases predicted by computational analysis.
AB  - Using iterative database searches, we identified a new subfamily of the
      AID/APOBEC family of RNA/DNA editing cytidine deaminases. The new subfamily,
      which is represented by readily identifiable orthologs in mammals, chicken, and
      frog, but not fishes, was designated APOBEC4. The zinc-coordinating motifs
      involved in catalysis and the secondary structure of the APOBEC4 deaminase domain
      are evolutionarily conserved, suggesting that APOBEC4 proteins are active
      polynucleotide (deoxy)cytidine deaminases. In reconstructed maximum likelihood
      phylogenetic trees, APOBEC4 forms a distinct clade with a high statistical
      support. APOBEC4 and APOBEC1 are joined in a moderately supported cluster clearly
      separated from AID, APOBEC2 and APOBEC3 subfamilies. In mammals, APOBEC4 is
      expressed primarily in testis which suggests the possibility that it is an
      editing enzyme for mRNAs involved in spermatogenesis.

PMID- 16082224
TI  - p53 codon 72 alleles influence the response to anticancer drugs in cells from
      aged people by regulating the cell cycle inhibitor p21WAF1.
AB  - A common polymorphism at codon 72 in p53 gene leads to an arginine to proline
      aminoacidic substitution which affects in an age-dependent manner the
      susceptibility of cells to undergo apoptosis after oxidative stress. Here we
      report that dermal fibroblasts from Proline allele carriers (Pro+) display a
      higher expression of p21WAF1 gene, in both basal conditions and after treatment
      with doxorubicin or camptothecin. This phenomenon is accompanied by a lower
      susceptibility of Pro+ cells to undergo apoptosis, a lower capability to over
      cross G1-S transition and an increased propensity to express markers of cell
      senescence, with respect to fibroblasts from Arginine homozygotes (Pro-). All
      these phenomena are particularly evident in cells from centenarians. We conclude
      that the functional difference between the two p53 codon 72 alleles exerts a
      broad impact on the capability of cell from aged people to respond to stressors
      such as cytotoxic drugs.

PMID- 16082225
TI  - Retinoblastoma family 2 is required in vivo for the tissue-specific repression of
      dE2F2 target genes.
AB  - In higher eukaryotes, the Retinoblastoma and E2F families of proteins control the
      transcription of a large number of target genes. Here, we have mutated the second
      Drosophila Retinoblastoma family gene (Rbf2), and contrasted the in vivo
      molecular functions of RBF2 with dE2F2, the only E2F partner of RBF2. Previous
      studies failed to uncover a unique role for RBF2 in E2F regulation. Here we find
      that RBF2 functions in concert with dE2F2 in vivo to repress the expression of
      differentiation markers in ovaries and embryos where RBF2 is highly expressed. We
      have compared the profiles of transcripts that are mis-expressed in ovaries,
      embryos and S2 cells where RBF2 function has been ablated and find that RBF2 and
      dE2F2 control strikingly different transcriptional programs in each situation. In
      vivo promoter occupancy studies point to the redistribution of dE2F/RBF complexes
      to different promoters in different cell types as one mechanism governing the
      tissue-specific regulation of dE2F/RBF target genes. These results demonstrate
      that RBF2 has a unique function in repressing E2F-regulated differentiation
      markers and that dE2F2 and RBF2 are required to regulate different sets of target
      genes in different tissues.

PMID- 16082226
TI  - Blockage of NF-kappaB induces serine 15 phosphorylation of mutant p53 by JNK
      kinase in prostate cancer cells.
AB  - The p53 tumor suppressor gene plays an important role during induction of
      apoptosis in cancer. In contrast, NF-kappaB prevents apoptosis in response to
      chemotherapeutic agents and is a critical regulator of cell survival. Despite the
      riches of information on the regulation of wild-type p53 function by
      phosphorylation, nothing is known about the modulation of mutant p53 activity by
      phosphorylation. Here we report that inhibition of NF-kappaB in DU145 prostate
      cancer cells results in p53 mutant phosphorylation at serine 15 (Ser15), leading
      to an increase of p53 stability, DNA binding and gain of function. Serine 15
      phosphorylation is due to GADD45alpha-dependent induction of JNK kinase, which
      can be blocked by SP600125, a JNK kinase inhibitor. Furthermore, inhibition of
      GADD45alpha by small interfering RNA blocks JNK activation and abrogates Ser15
      phosphorylation. Together, these results highlight the importance of Ser15
      phosphorylation in regulating the oncogenic function of mutant p53 and apoptosis
      induction in the context of the NF-kappaB/IkappaB signaling pathway.

PMID- 16082227
TI  - Human CDK2 inhibition modifies the dynamics of chromatin-bound minichromosome
      maintenance complex and replication protein A.
AB  - Minichromosome maintenance (MCM) proteins form a complex and possess helicase
      activity to unwind the DNA duplex and establish a replication fork. To assure
      that origins only fire once per cell cycle, the MCM complex is removed from
      chromatin and inactivated as cells exit S phase. In this report, we demonstrate
      that CDK2 depletion in human cells leads to an overall phosphorylation defect at
      mitosis with increased rereplication, correlated with the accumulation of
      chromatin-bound MCM proteins. We show that CDK2 suppression results in decreased
      MCM4 phosphorylation at multiple serine and threonine sites. In addition, CDK2
      inhibition induces an increase in chromatin-bound replication protein A (RPA)
      which should bind to single-stranded DNA regions, possibly establishing a
      replication intermediate that activates the ATR cascade. Finally, we observe that
      loss of CDK2 function in G1 delays replication initiation while it promotes
      rereplication in G2/M. Thus, by modulating the phospho-status of MCM4 and
      regulating origin firing, S phase CDK2 appears to be an integrated component of
      cellular machinery required for temporally controlling replication activity and
      maintaining genomic stability.

PMID- 16082228
TI  - Plagiarism is not acceptable in science or for cancer biology & therapy.

PMID- 16082231
TI  - The physiology and processing of pain: a review.
AB  - Despite the many advances in our understanding of the mechanisms underlying pain
      processing, pain continues to be a major healthcare problem in the United States.
      Each day, millions of Americans are affected by both acute and chronic pain
      conditions, costing in excess of $100 billion for treatment-related costs and
      lost work productivity. Thus, it is imperative that better treatment strategies
      be developed. One step toward improving pain management is through increased
      knowledge of pain physiology. Within the nervous system, there are several
      pathways that transmit information about pain from the periphery to the brain.
      There is also a network of pathways that carry modulatory signals from the brain
      and brainstem that alter the incoming flow of pain information. This article
      provides a review to the physiology and processing of pain.

PMID- 16082232
TI  - The endogenous opioid system and clinical pain management.
AB  - The endogenous opioid system is one of the most studied innate pain-relieving
      systems. This system consists of widely scattered neurons that produce three
      opioids: beta-endorphin, the met- and leu-enkephalins, and the dynorphins. These
      opioids act as neurotransmitters and neuromodulators at three major classes of
      receptors, termed mu, delta, and kappa, and produce analgesia. Like their
      endogenous counterparts, the opioid drugs, or opiates, act at these same
      receptors to produce both analgesia and undesirable side effects. This article
      examines some of the recent findings about the opioid system, including
      interactions with other neurotransmitters, the location and existence of receptor
      subtypes, and how this information drives the search for better analgesics. We
      also consider how an understanding of the opioid system affects clinical
      responses to opiate administration and what the future may hold for improved pain
      relief. The goal of this article is to assist clinicians to develop
      pharmacological interventions that better meet their patient's analgesic needs.

PMID- 16082233
TI  - Surgery-induced immunosuppression and postoperative pain management.
AB  - Surgery is well-known to result in the suppression of some immune functions;
      however, the role of perioperative pain has only recently been studied. Pain
      relieving anesthesia techniques and perioperative analgesia provide some
      protection against surgery-induced immune suppression and infectious surgical
      sequelae, although few studies also assess postoperative pain. Attributing a
      biological consequence to the observed immune alterations remains an issue in
      human studies, and the use of immune sensitive tumor models in animals enables
      the linking of immune changes with disease and a means by which to explore causal
      relationships among surgery-related pain, immune function, and metastatic
      development. There is strong evidence in animals that pain-relieving
      interventions significantly reduce the tumor-enhancing effects of undergoing and
      recovering from surgery. It cannot be assumed that animal findings are directly
      applicable to the human condition; however, if such relationships hold in humans,
      perioperative pain management becomes an important strategy for reducing
      postoperative sequelae.

PMID- 16082234
TI  - Acute musculoskeletal pain in the emergency department: a review of the
      literature and implications for the advanced practice nurse.
AB  - Acute pain assessment and management and their accurate documentation have been
      identified by The Joint Commission on the Accreditation of Healthcare
      Organization as significant components of the emergency department experience.
      Research studies have historically focused on the subjective perception of the
      physician or nurse for evidence of acute musculoskeletal pain assessment for the
      patient; however, the lack of interrater reliability between caregivers and
      patients has illustrated the need to evaluate the patient's perception of pain. A
      review of the literature for acute musculoskeletal pain in the emergency
      department shows that a patient's pain experience is often underestimated, and
      severity of pain often does not predict pain management. Relying on patient
      satisfaction surveys as a surrogate marker for effectiveness of pain management
      is inadequate, and factors, such as age, gender, or ethnicity, may contribute to
      a disparity in pain management. The purpose of this article is to review pain
      management practices for patients with acute musculoskeletal pain who present to
      the emergency department and to provide recommendations for advanced practice
      nurses working with this emergency department patient population. Promising areas
      for future research include targeting mechanisms of pain with specific
      medications, identifying vulnerable populations at risk for inadequate pain
      management, and universal use of a standardized pain rating scale.

PMID- 16082235
TI  - Management options for angina refractory to maximal medical and surgical
      interventions.
AB  - Despite the seemingly daily advances in the primary, secondary, and tertiary
      prevention for coronary artery disease, many patients will ultimately experience
      progression of their disease and experience angina refractory to further active
      treatment. In these patients, disabling angina occurs at rest or during simple
      activities of daily living. When this occurs, symptom management, a predominant
      focus of nursing, becomes the goal of care. Several medical and surgical
      alternatives are available to patients with refractory angina. Enhanced external
      counterpulsation and transmyocardial laser revascularization are Food and Drug
      Administration approved therapies that can be used to attempt to restore the
      balance of supply and demand. Modulation of sympathetic tone via procedures such
      as stellate ganglion blocks has also been employed. Other methods to control the
      pain are techniques that alter pain perception such as spinal opioids,
      transcutaneous electrical nerve stimulation, and spinal cord stimulation. Too few
      patients with refractory angina are referred for any of these palliative
      therapies. Armed with knowledge regarding these therapies, nurses will be better
      prepared to provide anticipatory guidance to patients and their families and to
      support the patient's hope for relief as they cope with this devastating
      condition.

PMID- 16082236
TI  - Orofacial pain--Part I: Assessment and management of musculoskeletal and
      neuropathic causes.
AB  - Orofacial pain is a common complaint, affecting the lives of millions of people
      around the world. Chronic orofacial pain often constitutes a challenging
      diagnostic problem that can be complicated by psychosocial factors and typically
      requires multidisciplinary treatment approaches. The fundamental prerequisite for
      successful management of orofacial pain is an accurate diagnosis. Generating a
      differential diagnosis, which will ultimately lead to a definite diagnosis,
      requires thorough knowledge of the diagnostic range of orofacial pain. There is a
      vast array of orofacial pain categories including: (1) musculoskeletal, (2)
      neuropathic, (3) vascular, (4) neurovascular, (5) idiopathic, (6) pain caused by
      local, distant, or systemic pathology, and (7) psychogenic. This article presents
      the salient clinical features and the therapeutic approaches for the various
      subtypes of musculoskeletal and neuropathic pain. Musculoskeletal pain is the
      most prevalent orofacial pain, with temporomandibular disorders and tension-type
      headache being the main examples. Neuropathic pain develops secondary to neural
      injury and/or irritation and can be distinguished into episodic, including
      trigeminal neuralgia and glossopharyngeal neuralgia, as well as continuous, such
      as herpetic and postherpetic neuralgia, traumatic neuralgia, and Eagle's
      syndrome.

PMID- 16082237
TI  - Orofacial Pain--Part II: Assessment and management of vascular, neurovascular,
      idiopathic, secondary, and psychogenic causes.
AB  - Chronic orofacial pain is a common health complaint faced by health practitioners
      today and constitutes a challenging diagnostic problem that often requires a
      multidisciplinary approach to diagnosis and treatment. The previous article by
      the same authors in this issue discussed the major clinical characteristics and
      the treatment of various musculoskeletal and neuropathic orofacial pain
      conditions. This second article presents aspects of vascular, neurovascular, and
      idiopathic orofacial pain, as well as orofacial pain due to various local,
      distant, or systemic diseases and psychogenic orofacial pain. The emphasis in
      this article is on the general differential diagnosis and various therapeutic
      regimens of each of these conditions. An accurate diagnosis is the key to
      successful treatment of chronic orofacial pain. Given that for many of the
      entities discussed in this article no curative treatment is available, current
      standards of management are emphasized. A comprehensive reference section has
      been included for those who wish to gain further information on a particular
      entity.

PMID- 16082238
TI  - Decision making for the patient who presents with acute dental pain.
AB  - Patients who require dental emergency care for pain or trauma may not be able to
      see a dental practitioner for treatment. The patients often seek care in
      alternative medical facilities when the symptoms are too severe to be managed by
      over-the-counter medications. Nurses, physicians, and allied medical staff may be
      required to triage these patients and provide palliative treatment until the
      patient is able to seek definitive dental treatment. By using criteria to assess
      the etiology of the dental pain and implementing possible alternative treatments,
      these patients can receive palliative care until dental treatment becomes
      accessible. With the potential for development of resistant forms of
      microorganisms, the indiscriminate use of antibiotics for dental pain is to be
      avoided. Occasionally, dental patients presenting to medical settings exhibit
      symptoms and signs of dental-related problems that are potentially life
      threatening. Identification of signs of impending life-threatening complications
      is of paramount importance, since prompt treatment will significantly affect the
      prognosis.

PMID- 16082239
TI  - Skin-to-skin contact (Kangaroo Care) analgesia for preterm infant heel stick.
AB  - The purpose of the study was to compare a heel stick conducted during Kangaroo
      Care (skin-to-skin contact) with the mother to a heel stick in a warmer in
      reducing premature infant physiologic and behavioral pain responses. Twenty-four
      premature infants in a university-based neonatal intensive care unit were
      recruited and randomized to 2 sequences: sequence A group received 3 hours of
      Kangaroo Care (with a heel stick in Kangaroo Care) followed by 3 hours in a
      warmer (with a heel stick in the warmer). Sequence B group had warmer care and a
      heel stick (in the warmer) before Kangaroo Care and a heel stick (in Kangaroo
      Care). Heart rate, respiratory rate, oxygen saturation, crying time, and
      behavioral state were measured before, during, and after heel stick. Repeated
      measures ANOVA and Mann Whitney U statistics were performed. Heart rate and
      length of crying in response to pain were significantly reduced during Kangaroo
      Care and the Kangaroo Care heel stick as compared to when infants were in the
      warmer and had a heel stick in the warmer. Three infants did not cry at all
      during the Kangaroo Care heel stick; infants slept more during Kangaroo Care than
      in the warmer. Kangaroo Care positioning before and during heel stick is a simple
      and inexpensive analgesic intervention to ameliorate pain in stable premature
      infants.

PMID- 16082240
TI  - Complex pain consultations in the pediatric intensive care unit.
AB  - The assessment and management of pain in children is not always easy and it is
      clearly more difficult in the critical care setting. Pain management is further
      complicated in this vulnerable population by the nature of their critical
      condition, the complexity and multidimensionality of their illness or injuries,
      and the intensity of emotions in this environment. A variety of pain syndromes
      are encountered in the pediatric intensive care unit, and the staff there may not
      be familiar with or comfortable managing these cases. Pain assessment and
      treatment can be more appropriately managed when guided by the experts of a
      multidisciplinary pediatric pain service.

PMID- 16082241
TI  - Nurse practitioners in pediatric critical care: results of a national survey.
AB  - The nurse practitioner in pediatric critical care is a distinct advanced practice
      nursing role that has seen a tremendous increase in development and
      implementation over the past 10 years. There is a paucity of literature on this
      unique and valuable role. A total of 74 nurse practitioners practicing in
      pediatric critical care were surveyed. Part I of the survey solicited descriptive
      information of the nurse practitioner including background, work environment,
      reporting structure, and salary. The respondents also identified their role
      responsibilities that included direct patient management, nursing and medical
      education, coordination of care, research, and consultation. Part II of the
      questionnaire addressed skill level and need for supervision for technical
      procedures and leadership activities. These respondents described expert or
      proficient skill levels for the majority of technical procedures (ie, lumbar
      puncture, central line placement) and leadership activities (ie, discharge
      planning, participation in medical rounds). This is the first published report to
      delineate the role of the nurse practitioner in pediatric critical care based on
      responses from a national survey.

PMID- 16082245
TI  - KIT (CD117): a review on expression in normal and neoplastic tissues, and
      mutations and their clinicopathologic correlation.
AB  - CD117 (KIT) is a type III receptor tyrosine kinase operating in cell signal
      transduction in several cell types. Normally KIT is activated (phosphorylated) by
      binding of its ligand, the stem cell factor. This leads to a phosphorylation
      cascade ultimately activating various transcription factors in different cell
      types. Such activation regulates apoptosis, cell differentiation, proliferation,
      chemotaxis, and cell adhesion. KIT-dependent cell types include mast cells, some
      hematopoietic stem cells, germ cells, melanocytes, and Cajal cells of the
      gastrointestinal tract, and neoplasms of these cells are examples of KIT-positive
      tumors. Other KIT-positive normal cells include epithelial cells in skin adnexa,
      breast, and subsets of cerebellar neurons. KIT positivity has been variably
      reported in sarcomas such as angiosarcoma, Ewing sarcoma, synovial sarcoma,
      leiomyosarcoma, and MFH; results of the last three are controversial. The
      variations in published data may result from incomplete specificity of some
      polyclonal antibodies, possibly contributed by too high dilutions. Also, KIT is
      expressed in pulmonary and other small cell carcinomas, adenoid cystic carcinoma,
      renal chromophobe carcinoma, thymic, and some ovarian and few breast carcinomas.
      A good KIT antibody reacts with known KIT positive cells, and smooth muscle cells
      and fibroblasts are negative. KIT deficiency due to hereditary nonsense/missense
      mutations leads to disruption of KIT-dependent functions such as erythropoiesis,
      skin pigmentation, fertility, and gastrointestinal motility. Conversely,
      pathologic activation of KIT through gain-of-function mutations leads to
      neoplasia of KIT-dependent and KIT-positive cell types at least in three
      different systems: mast cells/myeloid cells--mastocytosis/acute myeloid leukemia,
      germ cells--seminoma, and Cajal cells--gastrointestinal stromal tumors (GISTs).
      KIT tyrosine kinase inhibitors such as imatinib mesylate are the generally
      accepted treatment of metastatic GISTs, and their availability has prompted an
      active search for other treatment targets among KIT-positive tumors such as
      myeloid leukemias and small cell carcinoma of the lung, with variable and often
      nonconvincing results.

PMID- 16082246
TI  - Proximal-type epithelioid sarcoma: report of two cases in the perineum:
      differential diagnosis and review of soft tissue tumors with epithelioid and/or
      rhabdoid features.
AB  - The authors report two cases of perineal proximal-type epithelioid sarcoma in
      middle-aged men, age 51 and 43 years old. Both tumors were located in the right
      side. In the first patient a 7.5-cm, well-encapsulated tumor was completely
      excised. The second patient was a referral case with incomplete excision, but the
      computed tomography scan and magnetic resonance imaging showed a 14-cm
      nonencapsulated tumor involving the soft tissues of the inner thigh and perineum,
      as well as metastasis in right inguinal and retroperitoneal lymph nodes. Both
      neoplasms had a predominant solid pattern alternating with occasional discohesive
      areas. Both were composed of large oval to polygonal cells with vesicular nuclei,
      conspicuous nucleoli, and amphophilic to eosinophilic cytoplasm. Rhabdoid
      phenotype was identified in the second case only. The first neoplasm displayed
      15% necrosis, 7 mitoses per 10 high-power field, focal vascular invasion, and no
      extracapsular invasion. The other exhibited 60% necrosis, 12 mitoses per 10 high
      power fields, extensive vascular invasion, no distinct capsule, and invasion of
      the surrounding fatty tissue. Both were positive for vimentin, cytokeratin,
      epithelial membrane antigen, and CD34. Muscle-specific actin was negative in the
      first case and focally positive in the second. CD56 was positive in the second
      case and negative in the first case. Desmin, CD45, CD30, factor VIII, CD31, S100,
      HMB45, calretinin, and synaptophysin were negative in both. Since proximal-type
      epithelioid sarcoma can be confused with a number of other soft tissue tumors
      with epithelioid and/or rhabdoid features, the authors emphasize the
      immunohistochemical differential diagnosis.

PMID- 16082247
TI  - Caveolin-3 is a sensitive and specific marker for rhabdomyosarcoma.
AB  - Caveolin-3 (Cav-3) is a principal structural protein of caveolae membrane
      domains. Animal studies have revealed that Cav-3 is expressed in skeletal and
      cardiac myocytes but absent in other types of cells. Recent studies have shown
      that abnormalities in the Cav-3 gene are associated with some forms of muscular
      dystrophy, while skeletal muscle abnormalities have been observed in Cav-3
      transgenic and knockout mice. In this study the authors evaluated the
      distribution of Cav-3 in normal human tissues and compared the expression of Cav
      3 with that of myogenin and myoD1 in rhabdomyosarcoma (RMS), malignant mixed
      mullerian tumor (MMMT), and an array of neoplasms that mimic RMS to assess the
      utility of Cav-3 as a diagnostic marker for tumors with skeletal muscle
      differentiation. In nonneoplastic human tissues, crisp membrane staining for Cav
      3 was present in cardiac and skeletal myocytes and occasionally in arterial
      smooth muscle cells and prostatic stromal cells, while other cell types were
      negative for Cav-3. Eighty-eight percent (21/24) of RMS studied were positive for
      Cav-3. Positive staining was generally observed in the more maturely
      differentiated tumor cells but not the primitive tumor cells. Eight of nine cases
      of MMMT stained strongly with Cav-3 in their rhabdomyosarcomatous component but
      not in other components. Fifty-four other neoplasms (13 leiomyosarcomas, 8
      neuroblastomas, 5 lymphomas, 6 Wilms tumors without skeletal muscle
      differentiation, 5 Ewing sarcomas, 4 malignant fibrous histiocytomas, 4
      angiosarcomas, 6 malignant melanomas, and 3 synovial sarcomas) were negative for
      Cav-3 expression. Nearly all (96% [23/24]) cases of RMS were positive for
      myogenin, while 88% (21/24) were positive for myoD1. Primitive tumor cells showed
      significantly increased expression of myoD1 and myogenin; conversely, more
      differentiated tumor cells were negative or weakly stained. The
      rhabdomyosarcomatous component of MMMT stained focally with myogenin and myoD1,
      in contrast to the strong Cav-3 labeling in these cells. These results
      demonstrate that Cav-3 is specifically expressed in human cardiac and skeletal
      myocytes. Furthermore, its high specificity and relatively high sensitivity (88%)
      for tumors with skeletal muscle differentiation suggest that Cav-3 is a valuable
      marker for these tumors and may be used to assess the degree of differentiation
      of RMS and to identify residual tumor cells in post-chemotherapy specimens.

PMID- 16082248
TI  - Expression of p63 in diffuse large B-cell lymphoma.
AB  - The p63 gene, a homolog of the tumor suppressor gene TP53, maps to chromosome
      3q27-28, a region frequently displaying genomic amplification in squamous cell
      carcinomas. p63 is expressed in a variety of epithelial tissues and has been
      reported to be critical for the normal development of stratified epithelia,
      including skin epidermis. In a previous study, the authors reported the
      expression of p63 in occasional cells in the germinal center of lymph nodes and
      also observed p63 expression in B-cell lymphomas, among other tumor types
      surveyed in that analysis. The present study was conducted to further analyze the
      potential clinical significance of identifying p63 expression, assessing a larger
      cohort of well-characterized patients with diffuse large B-cell lymphoma (DLBCL)
      (n = 172 cases) and a panel of established lymphoma cell lines. p63 expression at
      the microanatomic detail was examined by immunohistochemistry using a monoclonal
      antibody (clone 4A4), while distinction of p63 isoforms was analyzed by Western
      blotting and reverse transcription-polymerase chain reaction using isoform
      specific primers. The authors found that a subset of DLBCL (32% of cases)
      expressed p63 in the nuclei of neoplastic lymphocytes. Examination of the
      different p63 isoforms revealed that the DeltaNp63 species was expressed by only
      one cell line, while the other p63 isoforms were found in most cell lines
      analyzed. The authors also observed that p63 expression correlated with high
      proliferative index, as assessed by Ki-67 immunostaining. Even though in
      univariate analysis p63 expression did not correlate with overall survival, the
      association of p63 with increased proliferative index suggests its involvement in
      DLBCL tumor progression.

PMID- 16082249
TI  - Localization of mesothelin in epithelial ovarian cancer.
AB  - Mesothelin is a cell surface glycoprotein that is present on normal mesothelial
      cells and overexpressed in several cancers. On immunohistochemical examination of
      a limited number of ovarian tumors, increased mesothelin expression has been
      previously noted. The authors evaluated mesothelin expression in 48 patients with
      ovarian cancer who were screened for participation in phase 1 studies of a
      recombinant immunotoxin targeting mesothelin. Eligibility criteria for
      participation in the studies included mesothelin expression by more than 30% of
      accessible tumor cells. Sections of formalin-fixed paraffin-embedded tumor
      specimens were evaluated for mesothelin expression by immunohistochemistry using
      the anti-mesothelin monoclonal antibody K1. Between September 2000 and January
      2003, 48 ovarian tumors were analyzed for mesothelin positivity. Mesothelin
      positivity was noted in 34 of the 48 cases evaluated (71%). These results show
      that mesothelin is expressed in most epithelial ovarian cancers and that
      mesothelin expression in ovarian cancers can be evaluated in archival material.
      Patients whose tumors express mesothelin could be eligible for participation in
      clinical trials of novel agents targeting mesothelin.

PMID- 16082250
TI  - Nuclear beta-catenin expression is rare and its potential association with short
      survival in colorectal signet-ring cell carcinoma.
AB  - Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer and the prognosis
      is usually very poor. The biologic pathways involved in its oncogenesis are
      unknown. beta-catenin, a key target in the Wnt-signaling pathway, is recognized
      to play an important role in the carcinogenesis in conventional colorectal
      carcinoma. This study explores the involvement of Wnt-signaling molecules beta
      catenin and cyclin D1, cell cycle regulators cyclin D3, proliferative index Ki
      67, apoptotic index, and angiogenic indicator CD31 in 20 colorectal SRCC paraffin
      embedded specimens. Results showed that there were 2 specimens with nuclear beta
      catenin and higher expression of cyclin D1 than the remaining 18 specimens.
      Surprisingly, those 2 patients had a much shorter survival of 6 months than the
      remaining 15 patients, who had around 24 months. Moreover, all colorectal SRCC
      specimens had an overexpression of cyclin D1, cyclin D3, and Ki-67, as well as
      much more angiogenesis and apoptosis than adjacent normal epithelial tissues. The
      authors make the preliminary comment that nuclear beta-catenin is a rare
      phenomenon in colorectal SRCC, but the involvement of it may indicate a worse
      prognosis with shorter survival than colorectal SRCC without nuclear beta-catenin
      expression. Besides, overexpression of cyclin D1, cyclin D3, Ki-67, and increased
      angiogenesis and apoptosis may play a vital role in promoting colorectal SRCC
      development.

PMID- 16082251
TI  - Utility of alpha-methylacyl coenzyme A racemase (p504s antibody) as a diagnostic
      immunohistochemical marker for cancer.
AB  - Alpha-methylacyl-coenzyme A racemase (AMACR; P504S) is a mitochondrial and
      peroxisomal enzyme involved in the metabolism of branched-chain fatty acid and
      bile acid intermediates. Recently, AMACR has been demonstrated to be
      overexpressed in localized and metastatic prostate cancer and in high-grade
      prostatic intraepithelial neoplasia but not in normal prostatic glands,
      suggesting that it may be an important tumor marker. This study examines AMACR
      expression in a variety of human cancers to assess its viability as a tumor
      marker in the clinical setting. Two hundred sixty-three cancers from different
      sites were examined in three multitumor tissue micro arrays, which included two
      or three tissue cores (1.0 mm in diameter) from each neoplastic and normal tissue
      specimen. Cancers studied included breast (94 cases), prostate (38), lung (28),
      endometrium (27), colon (29), ovary (26), and melanoma (21). Normal tissues in
      the microarray were prostate (15), lung (6), endometrium (5), colon (4), ovary
      (2), and skin (3). Sections were immunostained, after prior pressure cooker
      antigen retrieval, using rabbit monoclonal AMACR antibody (1:40) (Zeta Corp,
      Sierra Madre, CA) and horseradish peroxidase-labeled polymer conjugated secondary
      antibody (Envision, Dako, Carpinteria, CA). A section of prostate cancer and
      prostatic intraepithelial neoplasia was used as positive control. Protein
      expression was scored as negative, weak (faint cytoplasmic or granular apical
      staining), moderate (diffuse granular cytoplasmic stain), and strong (diffuse
      intense cytoplasmic stain). Only moderate and strong staining was considered as
      positive staining, based on prior work. AMACR protein overexpression was found in
      several cancers, including prostate (34/38 [89.5%]), colon (13/29 [44.8%]), lung
      (4/28 [14.3%]), melanoma (2/21 [9.5%]), endometrium (2/27 [7.4%]), and breast
      (3/94 [3.2%]). None of the ovarian cancers (26 cases) demonstrated AMACR
      overexpression. AMACR expression was not present in any of the normal tissues nor
      in benign prostatic tissue associated with prostate carcinomas. This study
      suggests that AMACR is potentially an important tumor marker, particularly for
      prostate and colon cancer. It may be a useful adjunct to an immunohistochemical
      panel employed in the differential diagnosis of colon versus ovarian and breast
      carcinoma; the latter two infrequently express AMACR.

PMID- 16082252
TI  - Role of immunohistochemistry in the diagnosis and progression of follicular
      epithelium-derived thyroid carcinoma.
AB  - Thyroid carcinoma derived from the thyroid hormone-producing follicular
      epithelium is the most common thyroid malignancy. While the morphologic diagnosis
      of conventional papillary thyroid carcinoma is simple, thyroid tumors with a
      follicular pattern are sometimes a diagnostic challenge. It is in the latter
      group of thyroid neoplasms that ancillary diagnostic tests such as
      immunohistochemistry may be of great help. Furthermore, while most differentiated
      thyroid carcinomas have an excellent prognosis, a subset of these tumors may
      progress to a poorly or undifferentiated phenotype indicating an aggressive
      biologic behavior that may lead to systemic spread and death. Application of
      immunohistochemistry to identify a subset of thyroid carcinoma that may progress
      to a biologically aggressive phenotype may help in the management of patients
      with thyroid carcinoma. This review discusses the role of immunohistochemistry in
      the diagnosis and progression of thyroid carcinoma is discussed.

PMID- 16082253
TI  - Expression of neuronal nuclear antigen (NeuN) in epithelial neuroendocrine
      carcinoma.
AB  - Expression of neuronal nuclei (NeuN), a mouse-derived neuronal-specific
      monoclonal antibody, has been found in almost all neuronal cell types throughout
      the nervous system. The authors have demonstrated NeuN immunoreactivity in 56% of
      epithelial neuroendocrine carcinomas (ENEC) (19/34): 4 of 7 (57%) grade 1 ENECs
      (carcinoid), 4 of 5 (90%) grade 2 ENECs (atypical carcinoid), and 11 of 22 (50%)
      grade 3 ENECs (small and large cell neuroendocrine carcinoma). Of the NeuN
      positive cases, the immunoreactivity was localized primarily in the cytoplasm in
      11 cases and in the nucleus in the remaining. Even though NeuN is not a highly
      sensitive marker for solo use, it would be useful as an adjunct in the panel
      immunohisto- chemistry of cases with histologic features suspicious of
      neuroendocrine differentiation.

PMID- 16082254
TI  - Cytomegalovirus-associated pulmonary septal capillary injury sine inclusion body
      change: a distinctive cause of occult or macroscopic pulmonary hemorrhage in the
      immunocompetent host.
AB  - The authors describe four patients with symptomatic lung disease morphologically
      representing a septal capillary injury syndrome temporally associated with
      serologic and culture evidence of active cytomegalovirus (CMV) infection but
      without classic cytopathic changes. The authors conducted a thorough review of
      clinical data, microscopic examination, and in situ hybridization to detect CMV
      mRNA encoding immediate early protein. The assay detects transcripts that encode
      early and immediate early proteins. In two cases additional tissue was available
      for direct immunofluorescent studies. The disease process in each of the patients
      was morphologically indistinguishable from the pattern of organ injury associated
      with autoimmune diseases including a small vessel microvascular injury syndrome
      involving skin and lung and immune complex- mediated glomerulonephritis.
      Cytopenias were seen in all cases, most commonly thrombocytopenia. All treated
      patients demonstrated improvement on combined ganciclovir and low-dose steroid
      therapy. CMV infection may be of pathogenetic importance in some cases of
      alveolar hemorrhage, especially when accompanied by peripheral blood cytopenia in
      otherwise healthy patients and if clinical worsening occurs in the setting of a
      traditional immunosuppressive regimen typically used to treat vasculitis.

PMID- 16082255
TI  - Basal lamina visualization using color image processing and pattern recognition.
AB  - In histologic assessment, the absence of basal lamina is a useful feature for
      distinguishing invasive malignancy from benign and in situ lesions. As this
      feature is not possible to assess in routine H&E sections, pathologists have
      instead relied on histochemical and immunohistochemical stains to show components
      of the basal lamina such as laminin or type IV collagen. Standard image
      processing software with the necessary image-processing toolbox (Matlab v5,
      Mathworks, Natick, MA) was used in a unique combination of color image processing
      and pattern recognition techniques to accentuate the collagenous stroma
      surrounding glands, which approximates basal lamina, in a series of benign, in
      situ, and invasive breast proliferations. Distinct differences in pattern were
      found between benign and invasive lesions, and also between in situ and malignant
      lesions, corresponding to that observed with type IV collagen immunostaining.
      Compared with immunostaining, this computer-generated method had a sensitivity of
      0.96, specificity of 0.89, positive predictive value of 0.92, negative predictive
      value of 0.89, positive likelihood ratio of 9.1, and negative likelihood ratio of
      0.042. Digital image processing serves as a less expensive and faster way of
      visualizing basal lamina and represents a useful adjunct to identify invasive
      malignancy in routinely stained sections. In addition, digital visualization of
      basal lamina is readily amenable to quantitative assessment, and the method
      provides a basis for the development of computer-based cancer diagnosis.

PMID- 16082256
TI  - Immunohistochemistry of tissue prepared by a molecular-friendly fixation and
      processing system.
AB  - A recently introduced histologic fixative (Universal Molecular Fixative [UMFIX])
      has been shown to preserve macromolecules in tissue at ambient temperature. When
      UMFIX-exposed tissues are processed by a formalin-free, microwave-assisted rapid
      processing system, the resulting paraffin blocks retain good histomorphology and
      intact nucleic acids suitable for expression microarray analysis. Because UMFIX
      may be used as an alternative to formalin, the authors set out to study the
      effect of this new fixation and processing system on immunohistochemistry (IHC)
      by analyzing a range of human neoplastic and non-neoplastic specimens. Parallel
      slices from surgically removed specimens were fixed in formalin and UMFIX and
      processed in a rapid microwave-assisted tissue processor. IHC was performed
      following routine procedures. The staining for those antibodies that normally
      required antigen retrieval was carried out with and without that step. The
      intensity and pattern of reactions were compared in 144 tissue samples fixed by
      the two methods using 70 monoclonal and polyclonal antibodies. The intensity of
      IHC reactions for most cytoplasmic antigens was generally equal or stronger in
      UMFIX tissues. This was particularly true with intermediate filaments and
      HercepTest, where the antigen retrieval step became unnecessary. Conversely,
      there was a decrease in the intensity of reactions for HepPar1, bcl-2, and three
      nuclear antigens (Ki-67, TTF-1, and estrogen receptor). Increasing their exposure
      times optimized the sensitivity of the latter four antibodies. The study shows
      that IHC staining results of tissues fixed in UMFIX and processed by the
      microwave-assisted system are comparable to those obtained on formalin-fixed,
      similarly processed specimens. There is an enhancement of the sensitivity of few
      antibodies in UMFIX-exposed tissue, rendering antigen retrieval unnecessary. This
      increased sensitivity may be due to the effect of eliminating formalin from
      fixation and processing or the microwave energy.

PMID- 16082257
TI  - Effect of heat-induced antigen retrieval following inconsistent formalin
      fixation.
AB  - The variable effects that inconsistent lengths of formalin fixation are known to
      have on the reactivity of tissue antigens were addressed by the application of a
      method for their heat-induced retrieval. Uniformly sized blocks of tonsil were
      fixed for increasing periods within 12 hours to 8 days before the heat retrieval
      and immunostaining of 30 tonsil antigens. The results were compared with their
      staining in the absence of heat retrieval, after prolongation of the standard
      retrieval time, and by use of a higher retrieval temperature. Consistent optimal
      staining of 26 of the 30 antigens was achieved despite the variable length of
      fixation. It is anticipated that the results will make a useful contribution to
      ongoing efforts toward the standardization of immunohistochemistry.

PMID- 16082258
TI  - A simple antigen retrieval method for the optimal demonstration of cyclin-D1
      overexpression in formalin-fixed paraffin-embedded cases of mantle cell lymphoma.
AB  - Successful diagnosis of mantle cell lymphoma (MCL) by immunohistochemistry is
      largely dependent on the successful demonstration of cyclin D1 overexpression in
      cases that fit clinical, morphologic, and immunophenotypical profiles. Accurate
      diagnosis in these cases is important due to the aggressive progression and poor
      survival times associated with this type of lymphoma. However, demonstration of
      cyclin D1 by immunohistochemistry on formalin-fixed, paraffin-embedded tissue is
      often fraught with technical difficulties, chiefly poor staining intensity
      largely due to insufficient antigen retrieval. The authors report a simple
      antigen retrieval technique that combines both heat and enzymatic treatment to
      demonstrate cyclin D1 overexpression. Furthermore, it appears that the antigen
      retrieval method is the key factor in the demonstration of cyclin D1, as
      detection systems with differing sensitivities (labeled streptavidin biotin [ABC]
      and dextran polymeric conjugate [Envision]) fail to demonstrate any significant
      differences in their staining intensities. This isa simple, cost-effective method
      that can be performed manually or can easily be adapted to suit automated
      staining systems.

PMID- 16082259
TI  - Immunohistochemical staining of epoxy resin sections of peripheral nerve.
AB  - The authors describe a simple and cost-effective method of immunostaining
      semithin epoxy resin sections of peripheral nerve for light microscopy with
      antibodies to myelin protein zero, peripheral myelin protein 22, myelin basic
      protein, and neurofilament protein 200 using a combined technique of surface
      etching with sodium ethoxide and heat-induced antigen retrieval.

PMID- 16082260
TI  - IHC comparison of antibodies 1D5 and 6F11 for estrogen receptor.

PMID- 16082262
TI  - Effects of minimum stimulation settings for the Med El Tempo+ speech processor on
      speech understanding.
AB  - OBJECTIVE: The aim of this study was to assess the effects of variations in the
      settings for minimum stimulation levels on speech understanding for adult
      cochlear implant recipients using the Med El Tempo+ speech processor. DESIGN:
      Fifteen patients served as listeners. The test material included sentences
      presented at a conversational level in noise (74 dB SPL at +10 dB signal-to-noise
      ratio), sentences presented at a soft level in a quiet background (54 dB SPL),
      consonants in "vCv" environment (74 dB SPL re: vowel peaks), and synthetic vowels
      in "bVt" environment (54 dB SPL re: vowel peaks). The patients' speech processors
      were programmed with minimum stimulation levels set to behavioral threshold, set
      to 10% of most comfortable loudness, and set to 0 muA. RESULTS: The level of
      speech understanding achieved in the behavioral threshold condition was not
      significantly different from that achieved in either the 10% of most comfortable
      loudness or 0 muA conditions for any test material. Only 2 of the 15 patients
      demonstrated performance differences of greater than 10 percentage points between
      the 0 muA condition and the behavioral threshold condition on more than a single
      test. CONCLUSIONS: Our results demonstrate that there are no grievous
      consequences, in terms of speech understanding, for setting minimum stimulation
      levels below behavioral thresholds. The time savings from setting thresholds to
      10% of MCL or 0 muA may be especially useful during the initial device fitting.

PMID- 16082263
TI  - Cochlear implant outcome is not influenced by the choice of ear.
AB  - OBJECTIVES: This study tested the hypothesis that patients with residual hearing
      in the nonimplanted ear had the same cochlear implant benefit whether the
      implanted ear had profound or severe hearing loss. DESIGN: A retrospective chart
      review of adult cochlear implant recipients with postlingual hearing loss.
      Patients were categorized according to the pure-tone average of the implanted and
      contralateral ears as (a) bilateral profound, (b) severe-profound, and (c)
      bilateral severe. The results of a test battery of spoken language measures were
      compared among patients belonging to these hearing categories at 6, 12, and 24
      months after surgery, using a t-test and multivariate regression analyses.
      RESULTS: The presence of residual hearing in one or both ears was associated with
      significantly higher postoperative speech perception scores compared with
      participants with bilateral profound hearing loss. Among participants with
      similar amounts of residual hearing in the nonimplanted ear, however, there was
      no difference in speech recognition scores between those with profound and those
      with severe hearing loss in the implanted ear. CONCLUSIONS: Among participants
      with asymmetric hearing loss, there is no additional benefit to implanting the
      better-hearing ear that can be preserved for use with a hearing aid for better
      speech understanding in noise and sound localization. These results suggest that
      the additional benefit received by patients with residual hearing is mediated by
      trophic effects on crossed pathways in the central nervous system and is
      independent of the preoperative functional status of the implanted ear.

PMID- 16082264
TI  - Prelexical vocalization in normal hearing and hearing-impaired infants before and
      after cochlear implantation and its relation to early auditory skills.
AB  - OBJECTIVES: To compare the vocalizations of hearing-impaired infants before and
      after cochlear implantation with those of a control group of hearing infants and
      to relate prelexical vocalizations by using the PRoduction Infant Scale
      Evaluation (PRISE) to early auditory skill attainments, using the Infant-Toddler
      Meaningful Auditory Integration Scale (IT-MAIS) in normal-hearing and hearing
      impaired (HI) infants before and after cochlear implantation. DESIGN: A total of
      187 infants participated in the study: 24 HI infants with severe-profound hearing
      loss (8 to 23 months of age) and 163 hearing infants (0.5 to 20 months of age).
      Prelexical vocalizations and early auditory skills were assessed by using parent
      questionnaires (PRISE and IT-MAIS, respectively) that reflect known milestones in
      the infant's vocal and auditory development. HI infant data were compared with
      hearing infant data according to chronological age and duration of device use
      (hearing aid or cochlear implant). RESULTS: Average PRISE score of aided HI
      infants before implantation was 50% or less (regardless of age). This score is
      comparable to that of hearing infants who are 6 to 7 months of age. After
      implantation, HI infants reached a score of 70% but did not reach normative
      performance. When HI infant data were compared with hearing infants by duration
      of device use, aided infants before implantation performed as well or worse than
      normative performance, whereas implanted infants performed as well as or better
      than hearing infants. Performance on individual PRISE questions showed limited
      ability by HI infants before implantation compared with hearing and implanted
      infants. A strong correlation was found between the IT-MAIS and the PRISE (r =
      0.93 and r = 0.83, for hearing and HI infants, respectively). CONCLUSIONS: The
      PRISE was found to be a versatile tool for implant team clinicians who are
      required to assess prelinguistic skills of infants. The findings suggest that
      early auditory skills are related to prelexical vocalization. The data also
      highlighted unanswered questions related to the importance of early fitting of
      hearing aids on vocalization before and after implantation.

PMID- 16082265
TI  - Spoken word recognition in children with cochlear implants: a five-year study on
      speakers of a tonal language.
AB  - OBJECTIVES: To study the effects of age at implantation and duration of implant
      use on the performance of spoken word recognition of pediatric cochlear
      implantees in a tonal language setting over a period of 5 years. DESIGN: Sixty
      four children, given implants between the ages 1:01 and 14:09 (years:months),
      were divided into three age groups. They were tested on open-set word recognition
      ability at seven time intervals from before surgery to 5 years after surgery.
      Analyses of variance with repeated measurements were used to examine the effect
      of their age at implantation and the duration of implant use. RESULTS: Duration
      of implant experience was significant in spoken word recognition across the three
      age groups (p < 0.01). Children given implants below the age of 3 years caught up
      with the performance of the older children at 12 months after implantation. The
      difference in score reached statistical significance at 2 and at 3 years after
      surgery (p = 0.03, p = 0.00). CONCLUSIONS: The performance of Cantonese-speaking
      children was similar to that of English-speaking children in that better outcomes
      were associated with longer implant experience as well as when implantation
      occurred at a younger age. The children implanted before the age of 3 and who had
      an implant experience of more than 2 years outperformed the children who were
      given implants after the age of 6 and also sustained these higher scores
      throughout 5 years of postimplant testing.

PMID- 16082266
TI  - A different approach to using neural response telemetry for automated cochlear
      implant processor programming.
AB  - OBJECTIVE: This study explores the theoretical relation between the
      psychophysically measured current levels required for sound processor fitting in
      cochlear implants and the objectively measured compound action potential
      threshold (as measured by Neural Response Telemetry, NRT). The objective was to
      gain understanding of the variability across implantees in this relation and
      determine possible ways (using objective measures) of improving the
      predictability of NRT thresholds for behavioral levels needed for mapping.
      DESIGN: A model of how rate of stimulation affects loudness is presented. The
      model can be used to understand differences among implantees in the way that rate
      affects loudness and hence explain the disappointing correlation between NRT and
      psychophysical measures. Suggestions are made, based on the model, for additional
      information that may improve the usefulness of NRT measurements. One such option
      (measuring the effect of interphase gap on NRT amplitude) was experimentally
      explored in eight subjects (26 electrodes). It was hypothesized that the current
      change required to maintain equal NRT amplitude when interphase gap was changed
      from 8 to 45 musec would be correlated with the offset between behavioral and NRT
      thresholds. RESULTS: The above hypothesis was not supported by the data, and
      several possible reasons for this outcome are discussed. CONCLUSIONS: The
      loudness model provides useful insights into why NRT thresholds are not good
      predictors of the behavioral levels needed for mapping and how NRT might be made
      more useful by additional objective information. These insights should be
      investigated in further experimental studies.

PMID- 16082267
TI  - Pharmacological enhancement of aural habilitation in adult cochlear implant
      users.
AB  - OBJECTIVE: The purpose of this report was to examine the preliminary data
      collected under a larger on-going feasibility study conducted with cochlear
      implant patients exploring the potential benefit of pharmacologically-enhanced
      aural rehabilitation therapy as a means of increasing speech tracking skills.
      DESIGN: Eight adult cochlear implant participants participated in a randomized,
      double-blind study and received either 10 mg d-amphetamine (Treatment group, N =
      4) or a placebo (Placebo group, N = 4) 60 minutes prior to a 1.5 hour intensive
      aural rehabilitation session occurring twice a week for two months. Treatment
      consisted of a multi-step rehabilitation program individualized for each
      participant to develop auditory-only speech tracking skills. Prior to and at the
      conclusion of the therapy sessions, SPECT rCBF imaging and speech tracking
      assessments were conducted. RESULTS: Speech tracking scores of the placebo and
      treatment groups were similar before the aural habilitation intervention. In the
      placebo group, speech tracking performance increased 13.5% for visual plus
      auditory and auditory only presentations as a function of aural habilitation
      alone. The 10 mg d-amphetamine-facilitated program resulted in minimal increases
      in visual plus auditory tracking scores (2%) but led to a 43% increase for
      auditory-only speech tracking. Regional cerebral blood flow measures indicated no
      substantial improvement of brain activation in the placebo group while both the
      extent and magnitude of primary and associative auditory cortex activations
      increased significantly with the pharmacologically enhanced treatment program.
      CONCLUSIONS: These data support previous studies indicating an accelerated
      acquisition of speech and language abilities in stroke patients receiving
      traditional speech therapy in combination with d-amphetamine. Data, however, are
      preliminary and further study is warranted.

PMID- 16082268
TI  - Genetic algorithms for adaptive psychophysical procedures: recipient-directed
      design of speech-processor MAPs.
AB  - OBJECTIVES: The goal of the research is to evaluate the application of genetic
      algorithms (GAs) in listener-directed optimization of audio-processing designs.
      We hypothesize that cochlear-implant recipients can use a GA-guided adaptive
      psychophysical search procedure to select useful designs from among a large
      number of speech processor MAPS. DESIGN: An adaptive psychophysical procedure was
      developed in which a listener's preferred four out of eight speech processor MAPs
      were updated according to a genetic algorithm. Experiments involving cochlear
      implant recipients were conducted to characterize both the convergence behavior
      of the adaptive procedure as well as properties of the MAPs optimized by the
      recipient. RESULTS: Results from five cochlear-implant recipients indicate that
      the adaptive procedure converges to useful speech processor MAPs within twenty
      iterations. CONCLUSION: The results suggest a means whereby a potentially large
      number of audio-processing designs can be searched efficiently by a human
      listener without requiring excessive amounts of feedback or prior knowledge about
      the listener's preferences. In the case of cochlear-implant recipients, it may be
      possible to use this procedure as an aid to the clinician in the fitting of a
      speech processor MAP.

PMID- 16082269
TI  - Two new directions in speech processor design for cochlear implants.
AB  - Two new approaches to the design of speech processors for cochlear implants are
      described. The first aims to represent "fine structure" or "fine frequency"
      information in a way that it can be perceived and used by patients, and the
      second aims to provide a closer mimicking than was previously possible of the
      signal processing that occurs in the normal cochlea.

PMID- 16082270
TI  - Spoken word recognition development in children with residual hearing using
      cochlear implants and hearing AIDS in opposite ears.
AB  - OBJECTIVE: With broadening candidacy criteria for cochlear implantation, a
      greater number of pediatric candidates have usable residual hearing in their
      nonimplanted ears. This population potentially stands to benefit from continued
      use of conventional amplification in their nonimplanted ears. The purposes of
      this investigation were to evaluate whether children with residual hearing in
      their nonimplanted ears benefit from bilateral use of cochlear implants and
      hearing aids and to investigate the time course of adaptation to combined use of
      the devices together. DESIGN: Pediatric cochlear implant recipients with severe
      sensorineural hearing loss in their nonimplanted ears served as participants. Ten
      children continued to use hearing aids in their nonimplanted ears after cochlear
      implantation; 12 children used their cochlear implants exclusively. Participants
      were tested longitudinally on spoken word recognition measures at 6-month
      intervals. The children who continued wearing hearing aids were tested in three
      sensory aid conditions: cochlear implants alone, hearing aids alone, and cochlear
      implants in conjunction with hearing aids. The children who did not continue
      hearing aid use were tested after surgery in their only aided condition, cochlear
      implant alone. RESULTS: The results suggest that children with severe hearing
      loss who continued using hearing aids in their nonimplanted ears benefited from
      combining the acoustic input received from a hearing aid with the input received
      from a cochlear implant, particularly in background noise. However, this benefit
      emerged with experience. CONCLUSIONS: Our findings suggest that it is appropriate
      to encourage pediatric cochlear implant recipients with severe hearing loss to
      continue wearing an appropriately fitted hearing aid in the nonimplanted ear to
      maximally benefit from bilateral stimulation.

PMID- 16082272
TI  - Uses of photodynamic therapy in premalignant and malignant lesions of the
      gastrointestinal tract beyond the esophagus.
AB  - Much has recently been written regarding the use of photodynamic therapy for the
      treatment of esophageal carcinoma and dysplastic Barrett's esophagus. This
      review, however, describes the clinical experience using photodynamic therapy
      with various photosensitizer agents for the treatment of diseases in other areas
      of the gut, especially the pancreaticobiliary tract where European studies have
      established the role of porfimer sodium photodynamic therapy in the management of
      patients with cholangiocarcinoma.

PMID- 16082273
TI  - Biopsychosocial issues in irritable bowel syndrome.
AB  - Irritable bowel syndrome is a biopsychosocial disorder that results from
      dysregulation of central and enteric nervous system function. It manifests as
      dysmotility and/or visceral hypersensitivity, and is modified by psychosocial
      processes. The interaction of the biopsychosocial factors determines the
      experience of the illness. An understanding of the biopsychosocial model of
      illness requires a shift from concepts traditionally taught in Western medical
      schools (biomedical reductionism and dualism) to that of multicausality, where
      biologic and psychologic factors interact to determine the disease and its
      experience or illness.

PMID- 16082274
TI  - The diagnostic accuracy of serologic markers in children with IBD: the West
      Virginia experience.
AB  - GOAL: To assess the sensitivity/specificity of the serologic markers: perinuclear
      antineutrophil cytoplasmic antibody (pANCA) and anti-saccharomyces cerevisiae
      antibody (ASCA) in children diagnosed with inflammatory bowel disease (IBD),
      living in West Virginia. BACKGROUND: In recent years, serologic markers have been
      used to differentiate between CD and UC diseases in children. The clinical
      usefulness of these markers in children was restricted by their low sensitivity
      and specificity. Racial and ethnic diversity may alter the accuracy of these
      markers in children. The demographic homogeneity of the West Virginia population
      may offer a better clinical setup to reassess the utility of those markers in
      children with IBD. STUDY: A retrospective analysis of all the charts of children
      diagnosed with IBD was performed at the gastroenterology clinics of Marshall
      University, Huntington, WV; and West Virginia University, Charleston Division,
      Charleston, WV. The diagnosis of IBD was established according to clinical,
      radiologic, and endoscopic data. Laboratory data and serum markers were recorded,
      and their accuracy to diagnose UC or CD was assessed. RESULTS: A total of 101
      charts were reviewed, of which only 90 (89%) included serologic markers and were
      considered for further analysis. Disease distribution included: UC-41, CD-44, and
      indeterminate colitis (IC)-7 (2 patients changed diagnosis after colectomy).
      Serum antibody pANCA had a sensitivity of 73% and specificity of 84% for UC, but
      only 16% and 35% for CD, respectively. Serum antibody ASCA had a sensitivity of
      58% and specificity of 92% for CD, but only 7% and 49% for UC, respectively. The
      outer membrane porin to Escherichia coli antibody (anti-OmpC) was available in 54
      (59%) children and demonstrated a very poor sensitivity for both diseases
      (sensitivity<11%). CONCLUSION: Despite our homogeneous patient population, pANCA
      and ASCA antibodies had an inadequate sensitivity/specificity for children with
      UC or CD. Those antibodies were not useful for our small number of patients with
      IC.

PMID- 16082275
TI  - Morphology of myenteric plexuses in the human large intestine: comparison between
      large intestines with and without colonic diverticula.
AB  - BACKGROUND: Large intestines with diverticula exhibit functionally abnormal
      peristaltic activity and elevated luminal pressure that may indicate functional
      changes in the myenteric plexus; however, no studies have investigated the
      characteristics of either normal or diverticula myenteric plexuses. METHODS:
      Tissue specimens obtained from 93 colorectal cancer patients without diverticula,
      14 patients with perforated diverticulitis, and 12 colorectal cancer patients
      with asymptomatic diverticula were included in this study. Myenteric plexuses and
      ganglion cells were counted per centimeter, and the area and maximum diameter of
      the nuclei of ganglion cells were measured using an image analyzer. RESULTS: The
      number of myenteric plexuses and ganglion cells per centimeter was significantly
      higher in the descending colon, sigmoid colon, and rectum than in the cecum,
      ascending colon, and transverse colon. The area of the nuclei of ganglion cells
      was significantly larger in the descending colon and sigmoid colon than in the
      cecum and ascending colon. Compared with large intestines without diverticula,
      the number of myenteric plexuses was significantly higher in large intestines
      with diverticula, whereas the number of ganglion cells decreased in both right
      sided and left-sided large intestines with perforated diverticulitis or
      asymptomatic diverticula. The area of the nuclei of ganglion cells was
      significantly smaller in large intestines with diverticula. CONCLUSION: The
      morphology of myenteric plexuses and the ganglion cells differs significantly
      among segments of the human large intestine. Large intestines with diverticula
      had significantly more plexuses but significantly fewer ganglion cells than large
      intestines without diverticula. The area of the nuclei of ganglion cells was also
      significantly smaller in large intestines with diverticula. Further studies are
      required to clarify how these changes are related to intestinal function and how
      they are involved in the etiology of diverticulosis.

PMID- 16082276
TI  - Ultrathin colonoscope with a diameter of 9.8 mm for total colonoscopy.
AB  - BACKGROUND: The pediatric colonoscope is superior to the standard colonoscope in
      some patients with a fixed, angulated colon. A colonoscope thinner than the
      pediatric one is thought to outperform even the pediatric colonoscope in such
      cases. This study was conducted to assess the efficacy of an ultrathin
      colonoscope, 9.8 mm in diameter, comparing it with pediatric and standard
      colonoscopes. METHODS: Three types of colonoscopes were used: ultrathin,
      pediatric, and standard. A total of 287 consecutive patients were assigned to
      three groups: ultrathin (n=94), pediatric (n=98), and standard (n=95). First
      assessment was the ratio of cecal intubation and the reasons for unsuccessful
      colonoscopy. The second was the time to cecal intubation. RESULTS: Cecal
      intubation rates were not different among three groups (96% in each). The main
      reasons for failed colonoscopy were looping in the ultrathin group, and
      angulation or stricture in the pediatric and standard groups. Mean time to the
      cecum was slightly longer in the ultrathin group (6.5 minutes) than the pediatric
      group (5.6 minutes) and standard group (6.1 minutes), but there were no
      significant differences among three groups. CONCLUSION: Colonoscopy with the
      ultrathin colonoscope was as successful as with the pediatric and standard
      colonoscopes. The advantage of the ultrathin colonoscope might be notable in
      cases with stricture or severe angulation.

PMID- 16082277
TI  - Influence of patient selection on the outcome of capsule endoscopy in patients
      with chronic gastrointestinal bleeding.
AB  - BACKGROUND: In chronic gastrointestinal bleeding, success rates in the range of
      48% to 76% have been reported for diagnosing clear bleeding sources using capsule
      endoscopy. The influence of patient selection on the numbers of positive findings
      yielded by capsule endoscopy is as yet unclear. METHODS: From April 2001 to June
      2003, capsule endoscopy was carried out in 74 of a total of 127 patients (58%)
      who presented for capsule endoscopy with a high suspicion of gastrointestinal
      bleeding in the small-bowel region. Seventy of the 74 patients were included in
      the analysis. This group of patients was divided into a study group (32 patients)
      and a post-study group (38 patients), and the two groups were compared. RESULTS:
      Stricter patient selection was carried out in the study group than in the post
      study group: 49% of those in the study group underwent capsule endoscopy,
      compared with 65% of those in the post-study group. The overall success rate for
      detecting relevant bleeding sources was 54%; in the study group, the rate was
      66%; whereas in the post-study group, it was only 45%. Significant differences
      observed between the two groups of patients included the lowest hemoglobin value
      (5.9+/-1.4 g/dL in the study group, compared with 7.7+/-2.1 g/dL in the post
      study group) and transfusion requirements (a median of 10 units in the study
      group, vs. 2 units in the post-study group). None of the patients who had a
      minimum hemoglobin value >or=10 g/dL had a positive capsule result. CONCLUSIONS:
      Patient selection has a considerable influence on the success rate of capsule
      endoscopy. In patients with chronic gastrointestinal bleeding, the minimum
      hemoglobin value and transfusion requirements appear to be the decisive
      parameters.

PMID- 16082278
TI  - Prevalence of celiac disease in Turkish children.
AB  - BACKGROUND: Celiac disease has emerged as a public health problem, and the
      disease prevalence varies among different races and nations. The present study
      was designed to investigate the prevalence of celiac disease in apparently
      healthy Turkish schoolchildren and to detect children with silent celiac disease.
      METHODS: Healthy school children, 6 to 17 years of age, which there are 72,000
      living in Erzurum were chosen as the study population. A total of 1,489 children
      were randomly selected by systematic sampling method. Samples were tested for
      anti- tissue transglutaminase IgA. Parents of the children who had positive test
      result were informed about the disease, and a small intestinal biopsy was
      proposed. A pathologist blinded to the serology results examined all biopsy
      specimens according to the modified Marsh criteria. RESULTS: A total of 1,263
      healthy school children were screened for celiac disease. Of subjects, 687
      (54.4%) were boys and 576 (45.6%) were girls. Mean age was 11.9+/-3.4 years
      (range, 6-17 years). None of the patients had IgA deficiency. Of 1,263 children,
      11 had positive anti-tissue transglutaminase IgA. Thus, the total seropositivity
      was 0.87%. Of seropositive children, 6 (54.6%) were boys and 5 (45.4%) were
      girls. We calculated the prevalence of celiac disease as 1:115. The prevalence of
      biopsy proven celiac disease was 1:158. CONCLUSIONS: In this first celiac disease
      prevalence study in Turkey, we found that celiac disease is highly prevalent in
      healthy schoolchildren. Children with iron deficiency anemia and malnutrition
      should be evaluated more carefully with the understanding of the high celiac
      disease prevalence in Turkey.

PMID- 16082279
TI  - Effects of a specially designed fermented milk product containing probiotic
      Lactobacillus casei DN-114 001 and the eradication of H. pylori in children: a
      prospective randomized double-blind study.
AB  - GOALS: To determine the efficacy of triple therapy supplemented with a specially
      designed fermented milk product containing specific probiotic Lactobacillus casei
      (L. casei) DN-114 001 strain on Helicobacter pylori eradication in children.
      BACKGROUND: Lactobacillus species possess in vitro activity against H. pylori.
      There are no consistent data on the impact of eradication therapy supplemented
      with probiotics on H. pylori cure rates in childhood in vivo. STUDY: Multicenter,
      prospective, randomized, double-blind controlled study. Eighty-six symptomatic H.
      pylori-positive children were randomized either to receive the control treatment
      of omeprazole, amoxicillin, and clarithromycin (OAC) for 7 days or the test
      treatment of omeprazole, amoxicillin, and clarithromycin for 7 days supplemented
      with fermented milk (Actimel) containing L. casei DN-114 001 (OAC-LC), for 14
      days. H. pylori status was assessed at 4 weeks following therapy using two
      noninvasive tests. RESULTS: Intention-to-treat (ITT) based eradication rates for
      the OAC-LC group were 84.6% (95% CI, 71.2%-95.5%), and 91.6% (95% CI, 76.9%
      98.2%) by per-protocol (PP) analysis. Eradication in the OAC group was 57.5% (95%
      CI, 42.2%-72.3%) in the ITT set and 61.3% (95% CI, 44.4%-75.0%) in the PP group.
      Eradication success was higher in the OAC-LC group compared with the OAC group in
      both ITT (P=0.0045) and PP analysis (P=0.0019). Primary resistance for
      clarithromycin could be determined in 21.2%. Side effects were infrequent. Drug
      compliance was good throughout the study. CONCLUSION: Supplementation with
      fermented milk, containing live special probiotic L. casei DN-114 001, confers an
      enhanced therapeutic benefit on H. pylori eradication in children with gastritis
      on triple therapy.

PMID- 16082280
TI  - Smoking and hyperpepsinogenemia are associated with increased risk for duodenal
      ulcer in Helicobacter pylori-infected patients.
AB  - BACKGROUND: Although Helicobacter pylori has been established as a major
      etiologic factor of chronic gastritis and makes an important contribution to
      peptic ulceration, the reason why H. pylori causes different gastroduodenal
      diseases in different people is at present not clear. GOALS: The aim of this
      study is to identify risk factors associated with duodenal ulcers in H. pylori
      infected patients in a multivariate context. STUDY: Demographic data, personal
      habits, stressful life events, psychologic distress, severity of histology of
      antral mucosa, and serum pepsinogen I concentrations were studied in 54
      consecutive dyspeptic patients with duodenal ulcers and 40 patients with
      functional dyspepsia. RESULTS: As compared with functional dyspepsia patients,
      duodenal ulcer patients had more smokers (53.7% vs. 12.5%, P=0.000), higher
      pepsinogen I levels (median 96.0 vs. 74.5 ng/mL; P=0.002), more males (74.1% vs.
      42.5%, P=0.004), more single (22.6% vs. 7.5%, P<0.05), and less in religion
      belief (44% vs. 70%, P<0.05). Only smoking remained significant on multivariate
      analysis (odds ratio=10.86, 95% CI=2.92-40.41, P<0.001). Among nonsmokers, only
      serum pepsinogen I level was found higher in duodenal ulcer patients as compared
      with functional dyspepsia patients (88 vs. 71, P<0.05). CONCLUSIONS: Smoking and
      hyperpepsinogenemia are associated with increased risk for duodenal ulcer in H.
      pylori-infected patients.

PMID- 16082281
TI  - Idiopathic myointimal hyperplasia of mesenteric veins: a rare mimic of idiopathic
      inflammatory bowel disease.
AB  - Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and
      poorly understood disease that occurs in the rectosigmoid colon of predominantly
      young, previously healthy male patients. IMHMV typically requires segmental
      resection due to complications after a relatively protracted clinical course.
      This disease presents a challenging diagnostic dilemma for the clinician because
      it is initially often confused with chronic idiopathic inflammatory bowel
      disease. We report a case of IMHMV, illustrate endoscopic and histopathologic
      features, and review key characteristics of this rare entity.

PMID- 16082282
TI  - Drug-induced pancreatitis: an update.
AB  - BACKGROUND AND AIMS: Many frequently prescribed drugs are suspected to cause
      acute pancreatitis (AP). The goal of this paper is to bring to light the often
      occult but real problem of drug-induced pancreatitis (DIP). METHODS: We searched
      the National Library of Medicine/Pubmed for reported cases of DIP from 1966 to
      April 30, 2004. Medications implicated in AP are classified based on the strength
      of evidence into one of three classes of drugs associated with pancreatitis. We
      reviewed the top 100 prescription medications in the United States for their
      association with AP. RESULTS: Class I medications (medications implicated in
      greater than 20 reported cases of acute pancreatitis with at least one documented
      case following reexposure): didanosine, asparaginase, azathioprine, valproic
      acid, pentavalent antimonials, pentamidine, mercaptopurine, mesalamine, estrogen
      preparations, opiates, tetracycline, cytarabine, steroids,
      trimethoprim/sulfamethoxazole, sulfasalazine, furosemide, and sulindac. Class II
      medications (medications implicated in more than 10 cases of acute pancreatitis):
      rifampin, lamivudine, octreotide, carbamazepine, acetaminophen, phenformin,
      interferon alfa-2b, enalapril, hydrochlorothiazide, cisplatin, erythromycin, and
      cyclopenthiazide. Class III medications (all medications reported to be
      associated with pancreatitis). Of the top 100 most frequently prescribed
      medications in the United States, 44 have been implicated in AP, 14 of them fall
      into either Class I or II of medications associated with AP. CONCLUSIONS: Among
      adverse drug reactions, pancreatitis is often-ignored because of the difficulty
      in implicating a drug as its cause. The physician should have a high index of
      suspicion for DIP, especially in specific subpopulations such as geriatric
      patients who may be on multiple medications, HIV+ patients, cancer patients, and
      patients receiving immunomodulating agents.

PMID- 16082283
TI  - A retrospective comparison of outcomes using three different precut needle knife
      techniques for biliary cannulation.
AB  - GOALS: To assess the outcome differences following different precut biliary
      sphincterotomy needle-knife techniques. BACKGROUND: Precut biliary needle-knife
      sphincterotomy (NKS) allows biliary access when standard cannulation techniques
      fail. Little comparative data exist on the outcome of precut NKS. STUDY:
      Retrospective comparison of outcome differences of three NKS techniques performed
      by three pancreaticobiliary endoscopists at a tertiary referral center. RESULTS:
      A total of 139 consecutive biliary NKS were performed. In 44 cases (technique A),
      NKS was performed using a precut fistulotomy technique avoiding the papillary
      orifice, with pure cutting current, and occasional pancreatic duct (PD) stenting
      (6 of 44). In 47 cases (technique B), NKS was performed starting from the
      papillary orifice cutting upward with blended current, and no PD stenting. In 48
      cases (technique C), NKS was performed as B but using pure cutting current and
      frequent PD stenting (15 of 48). NKS was successful in 95.5%, 95.7%, and 89.6% at
      initial endoscopic retrograde cholangiopancreatography and 100%, 97.8%, and 95.6%
      after a second endoscopic retrograde cholangiopancreatography. Total
      complications were not significantly different between the three groups; however,
      a lower incidence of pancreatitis occurred using technique A compared with
      techniques B and C (not significant). CONCLUSIONS: NKS techniques result in a
      high success rate of biliary cannulation with a similar overall complication
      rate. Avoiding cutting at the papillary orifice may reduce the risk of
      pancreatitis. When cutting at the papillary orifice, pancreatic duct stenting,
      pure cutting current, or both may reduce the incidence of pancreatitis.

PMID- 16082284
TI  - More severe parenchymal injury in chronic hepatitis C acquired by recent
      injection drug use.
AB  - OBJECTIVE: Histologic liver injury is reported to be less severe in persons who
      acquire hepatitis C through injection drug use (IDU) than by blood transfusion.
      Because age correlates with histologic severity, it may be that differences
      between routes of acquisition reflect the younger age of most drug abusers. The
      early histopathologic changes of hepatitis C acquired through IDU are less
      defined, probably because of the lack of liver biopsy material from a cohort of
      patients not long after initial exposure. The availability of material from a
      cohort of patients who had liver biopsy for IDU-related hepatitis C in the 1970s
      enabled us to compare the histology with that of current patients. METHODS: Liver
      biopsies of a group of injection drug users (n=70, all males; mean age, 27.6
      years, designated as Group 1) in the 1970s cohort were compared with biopsies of
      patients (n=63, all males; mean age, 48 years, designated as Group 2, 23 who
      admitted past IDU) entering a treatment trial in 1999. All patients were positive
      for anti-HCV at the time of biopsy. RESULTS: The histologic features of the 23
      patients in Group 2 with a history of IDU did not differ significantly from the
      other 40 patients who denied past IDU. Using a modified Histologic Activity Index
      (HAI), there was no difference between Group 1 and Group 2 in portal inflammation
      or periportal injury. However, parenchymal (lobular) injury and inflammation was
      significantly (P<0.0001) greater in Group 1 than Group 2. Fibrosis was
      significantly (P=0.014) greater in Group 2. CONCLUSIONS: The degree of
      parenchymal injury was greater in Group 1 than Group 2, perhaps because they were
      closer to the time of exposure or possibly because of a stronger immunologic
      response in younger patients. The degree of hepatic fibrosis was greater in Group
      2, suggesting that progression with age may be the natural history of chronic
      hepatitis C.

PMID- 16082285
TI  - Gamma-glutamyl transferase (GGT) as an independent predictive factor of sustained
      virologic response in patients with hepatitis C treated with interferon-alpha and
      ribavirin.
AB  - BACKGROUND: Recently, gamma-glutamyl transferase (GGT) has been investigated as a
      predictive factor for therapy response in hepatitis C patients, but so far its
      value in pretreatment screening has not been established. Therefore, this study
      aimed at evaluating GGT as an independent predictive factor for the response to
      treatment with interferon-alpha and ribavirin in hepatitis C virus (HCV)-infected
      patients. METHODS: Naive chronic hepatitis C patients undergoing a 6-month follow
      up after interferon-alpha and ribavirin therapy had their sustained virologic
      response (SVR) analyzed according to age, sex, body mass index, GGT levels,
      genotype, and liver histology by use of a multivariate logistic regression model.
      RESULTS: Of the 211 patients studied with a mean age of 48+/-10 years, 125 (59%)
      were males. Overweight was detected in 47% of patients. Genotype 1 was detected
      in 141 (75%) of the 187 patients tested. Cirrhosis was present in 67 (32%). A
      high pretreatment GGT level was observed in 134 (63%). SVR was obtained in 84
      (40%) patients. In the final logistic regression model, the variables
      independently associated with SVR were GGT (P<0.001), genotype (P<0.001), and
      liver histology (P<0.001). CONCLUSION: A normal GGT level is an independent
      predictive factor for SVR in HCV-infected patients and should be considered for
      pretreatment screening.

PMID- 16082286
TI  - Physical and psychosocial contributors to quality of life in veterans with
      hepatitis C not on antiviral therapy.
AB  - BACKGROUND AND AIMS: Treatment-naive hepatitis C virus (HCV)-infected patients
      report impaired health-related quality of life (HRQOL), although causes are
      unclear. Psychosocial factors may be major determinants of HRQOL. METHODS: We
      administered a general (Short Form-36; SF-36) and a liver-specific (Chronic Liver
      Disease Questionnaire; CLDQ) HRQOL measure to 62 HCV-infected veterans being
      considered for antiviral therapy. Psychosocial assessment included the Structured
      Clinical Interview for DSM-IV Axis I Disorders/Non-Patient (SCID-I/NP), Beck
      Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Abbreviated Cook
      Medley (ACM) anger measure, and Medical Outcomes Study Social Support Measure
      (SSM). We examined the potential determinants of HRQOL, including psychosocial
      measures, demographic measures (age, sex, race/ethnicity), clinical measures
      (presence of cirrhosis, comorbid medical conditions), and viral data
      (quantitative PCR). RESULTS: SF-36 scores were significantly lower in HCV
      infected patients than published U.S. population norms but similar to those
      reported by previous studies of HCV-infected samples. CLDQ scores were very
      similar to those reported by previous studies. Demographic, clinical, and viral
      indicators were not statistically associated with HRQOL, and neither was the
      presence of a substance abuse or psychotic disorder. Lower BDI-II and BAI scores
      were associated with better general and disease-specific HRQOL. Lower SSM scores
      were associated with lower scores on SF-36 but not CLDQ; however, this effect did
      not persist in multiple linear regression analyses. In these, BDI-II was the
      strongest independent predictor of both SF-36 and CLDQ. CONCLUSIONS: Psychosocial
      factors, especially depression, are strong indicators of impaired HRQOL for HCV
      infected veterans not receiving antiviral therapy. Screening and treatment of
      psychosocial factors is recommended.

PMID- 16082287
TI  - Treatment of chronic hepatitis C virus infection via antioxidants: results of a
      phase I clinical trial.
AB  - BACKGROUND: The pathogenesis of chronic hepatitis C virus (HCV) infection is
      associated with a defective host antiviral immune response and intrahepatic
      oxidative stress. Oxidative stress and lipid peroxidation play major roles in the
      fatty liver accumulation (steatosis) that leads to necro-inflammation and
      necrosis of hepatic cells. Previous trials suggested that antioxidative therapy
      may have a beneficial effect on patients with chronic HCV infection. AIMS: To
      determine the safety and efficacy of treatment of chronic HCV patients via a
      combination of antioxidants. METHODS: Fifty chronic HCV patients were treated
      orally on a daily basis for 20 weeks with seven antioxidative oral preparations
      (glycyrrhizin, schisandra, silymarin, ascorbic acid, lipoic acid, L-glutathione,
      and alpha-tocopherol), along with four different intravenous preparations
      (glycyrrhizin, ascorbic acid, L-glutathione, B-complex) twice weekly for the
      first 10 weeks, and followed up for an additional 20 weeks. Patients were
      monitored for HCV-RNA levels, liver enzymes, and liver histology. Assessment of
      quality of life was performed using the SF-36 questionnaire. RESULTS: In one of
      the tested parameters (eg, liver enzymes, HCV RNA levels, or liver biopsy score),
      a combination of antioxidants induced a favorable response in 48% of the patients
      (24). Normalization of liver enzymes occurred in 44% of patients who had elevated
      pretreatment ALT levels (15 of 34). ALT levels remained normal throughout follow
      up period in 72.7% (8 of 11). A decrease in viral load (one log or more) was
      observed in 25% of the patients (12). Histologic improvement (2-point reduction
      in the HAI score) was noted in 36.1% of the patients. The SF-36 score improved in
      26 of 45 patients throughout the course of the trial (58% of the patients).
      Treatment was well tolerated by all patients. No major adverse reactions were
      noted. CONCLUSIONS: These data suggest that multi antioxidative treatment in
      chronic HCV patients is well tolerated and may have a beneficial effect on necro
      inflammatory variables. A combination of antiviral and antioxidative therapies
      may enhance the overall response rate of these patients.

PMID- 16082288
TI  - Erythromycin-associated cholestatic hepatitis and liver dysfunction in children:
      the British experience.

PMID- 16082289
TI  - Serum adiponectin concentration in patients with hepatitis C virus.

PMID- 16082290
TI  - Esophageal metastasis from rectal carcinoma.

PMID- 16082291
TI  - Which combination should be preferred in the management of children with chronic
      hepatitis B infection?

PMID- 16082292
TI  - Head elevation may not be always safe in the treatment of GERD.

PMID- 16082293
TI  - Trauma and hallucinatory experience in psychosis.
AB  - Recent research indicates that there may be phenomenological, symptom, and
      diagnostic associations between trauma and hallucinations. However, the nature of
      the relationship is poorly understood from a psychological perspective. We report
      a theoretically informed phenomenological study. From descriptions of reported
      traumas and hallucinations, we assessed the rates of four types of hypothesized
      association between traumas and hallucinations (direct, indirect, stress, and
      none) in 75 participants with nonaffective psychosis. In a subgroup who had
      experienced trauma (N = 40), 12.5% had hallucinations with similar themes and
      content to their traumas, 45% had hallucinations in which the themes were the
      same but not the content, and 42.5% had no identifiable associations between
      their hallucinations and previously experienced trauma. Traumas rated as
      intrusive were significantly associated with hallucinations rated as intrusive,
      although intrusive hallucinations were not associated with traumas in general.
      The traumas most likely to be associated with hallucinations were sexual abuse
      and bullying.

PMID- 16082294
TI  - The impact of early trauma and recent life-events on symptom severity in patients
      with conversion disorder.
AB  - Although the presence of psychological stress factors in the evolution of
      conversion symptoms forms an important criterion for the DSM-IV diagnosis of
      conversion disorder, little is known about the nature and timing of these stress
      factors. Fifty-four patients with conversion disorder and 50 control patients
      with an affective disorder were screened for life events experienced in the year
      before the symptom onset. Conversion patients did not differ from control
      patients in the number or severity of life events, but showed a significant
      relation between the recent life events and the severity of conversion symptoms.
      Especially life events with respect to work and relationships contributed to this
      effect. These results remained when controlling for the previously found effects
      of childhood traumatization on the severity of conversion symptoms. The findings
      imply that conversion symptoms may be elicited by a complex of early and later
      negative life events and that traditional unifactorial trauma-theories of
      conversion disorder should be replaced by multifactorial stress models.

PMID- 16082295
TI  - PTSD and Treatment Adherence: the role of health beliefs.
AB  - Health beliefs have been shown to influence a myriad of medical treatment
      decisions. More recently, the impact of health beliefs on treatment decisions for
      mental illness has become a focus of study. This study examines the health
      beliefs and treatment behavior of veterans with posttraumatic stress disorder
      (PTSD). Using standard survey methodology, we assessed beliefs about the cause of
      PTSD, expected duration and controllability of symptoms, and life consequences of
      having PTSD. Treatment participation and medication compliance were assessed, as
      were common treatment correlates, such as patient-provider relationships, dosing
      frequency, side effect severity, number of prescribed medications, and use of
      drugs or alcohol to control PTSD symptoms. Explanatory models of PTSD, perceived
      controllability, and use of benzodiazepines were found to predict psychiatric
      medication use. Negative life consequences of PTSD were associated with
      participation in psychotherapy. Assessment of health beliefs may help providers
      to understand their patients' treatment behavior and to facilitate treatment
      engagement.

PMID- 16082296
TI  - Concerns of Capitol Hill staff workers after bioterrorism: focus group
      discussions of authorities' response.
AB  - Systematic studies of mental health effects of bioterrorism on exposed
      populations have not been carried out. Exploratory focus groups were conducted
      with an exposed population to provide qualitative data and inform empirical
      research. Five focus groups of 28 political worker volunteers were conducted 3
      months after the October 15, 2001, anthrax attack on Capitol Hill. More than 2000
      transcribed focus group passages were categorized using qualitative software. The
      category with the most items was authorities' response (23% passages), and much
      of this discussion pertained to communication by authorities. The category with
      the fewest items was symptoms (4%). Identified issues were less within
      individuals and more between them and authorities. Risk communication by
      authorities regarding safety and medical issues was a prominent concern among
      Capitol Hill office staff workers regarding the anthrax incident on Capitol Hill.
      This suggests focus on risk communication in developing interventions, but more
      systematic investigation is needed.

PMID- 16082297
TI  - Concordance of reports of mental health functioning by adolescents and their
      caregivers: a comparison of European, African and Latino Americans.
AB  - The purpose of this study was to examine the concordance of parental and
      adolescent reports of adolescents having emotional and behavioral problems. Data
      were collected from youths (age 11-17) and adult caregivers from a community
      based sample of households. The sample consisted of 4175 youths and their
      caregivers (37.8% European, 35.0% African, 25.4% Latino, and 1.8% other
      American). Indicators of emotional and/or behavioral problems were global
      indicators: perceived mental health, life satisfaction, happiness, interpersonal
      problems at home, and problems at school. Overall, parent-child concordance on
      the indicators of mental health was low, with a mean kappa value of 0.12. In
      multivariate analyses, European American parent-youth dyads were significantly
      more likely to be concordant on reports of perceived mental health, problems at
      home, and problems at school than African American and Latino dyads. Our data
      suggest that ethnicity is a significant factor in parental labeling and awareness
      of adolescent mental health problems. Future research should examine whether the
      extent to which greater lack of concordance on the indicators of mental health by
      minority parent-child dyads plays a role in entry into and retention in mental
      health care.

PMID- 16082298
TI  - Guarded self-disclosure predicts psychological distress and willingness to use
      psychological services among East Asian immigrants in the United States.
AB  - This study examined the relationship between guarded self-disclosure,
      psychological distress, and willingness to use psychological services if
      distressed among 170 (88 male, 82 female) East Asian immigrants in the United
      States. Participants were administered a battery of psychometrically established
      measures. Participants who endorsed overall guarded self-disclosure, self
      concealment (i.e., unwillingness to reveal affect to others), or conflict
      avoidance (i.e., maintenance of harmony via suppression of feelings) were
      significantly more likely to report psychological distress and were significantly
      less likely to report willingness to use psychological services. While conflict
      avoidance was a significant independent predictor of psychological distress, self
      concealment was a significant independent predictor of willingness to use
      psychological services. These findings point to the importance of assessing
      multiple facets of guarded self-disclosure, which appear to be differentially
      associated with psychological distress and willingness to use psychological
      services.

PMID- 16082299
TI  - Postconcussional disorder: Are the DSM-IV criteria an improvement over the ICD
      10?
AB  - Little is known about the characteristics and outcomes of patients diagnosed with
      postconcussional disorder (PCD) under the provisionally proposed criteria in the
      DSM-IV and how they differ from patients diagnosed with postconcussional syndrome
      (PCS) under the International Classification of Diseases, 10th edition clinical
      (ICD-10) criteria. This study investigated differences in outcome based on a
      diagnosis of PCD (DSM-IV) versus PCS (ICD-10 clinical criteria) as to which
      criteria set might be preferred for clinical practice. A consecutive series of
      adult patients with mild (N = 319) to moderate (N = 21) traumatic brain injury
      was assessed at 3 months postinjury with a brief neuropsychological battery and
      measures of specific outcome domains. In two separate series of analyses,
      patients with PCD were compared with those without PCD, and those with PCS were
      compared with those without PCS. Although the two criteria sets resulted in
      markedly different incidence rates, there was no substantial pattern of
      differences between the DSM-IV and ICD-10 in the outcome domains of psychiatric
      symptoms and disorders, social and community integration, health-related quality
      of life, or global outcome as measured by the Glasgow Outcome Scale-Extended. In
      spite of significant differences between the two diagnostic criteria sets and
      different incidence rates for PCD/PCS, outcome in all measured domains was very
      similar at 3 months postinjury. There is no compelling evidence, based on these
      outcome domains, to suggest which of the two diagnostic criteria sets should be
      clinically preferred.

PMID- 16082300
TI  - Building primary care practitioners' attitudes and confidence in mental health
      skills in a post-conflict society: a Cambodian example.
AB  - Our program attempted to integrate community mental health in primary care
      settings in Cambodia and to evaluate the effects of training on local providers.
      The training program underwent an extensive evaluation to determine its impact on
      the mental health knowledge, confidence in performing medical and psychiatric
      procedures, skills and attitudes of its trainees. One hundred four Cambodian
      primary care practitioners (PCPs) were trained in a primary care setting in Siem
      Reap, Cambodia, over a 2-year period. There was a significant improvement in
      PCPs' confidence in all clusters of medical and psychiatric procedures
      (counseling, medical evaluation, prescribing medications, psychiatric diagnosis,
      assessing risk for violence, traditional treatments, and treating trauma victims)
      comparing baseline to posttraining and baseline to 2-year follow-up (p < 0.05).
      Only confidence in prescribing psychotropic medications improved from
      posttraining to 2-year follow-up. This study supports the feasibility of training
      PCPs in a culturally effective manner in a postconflict society.

PMID- 16082301
TI  - A pilot feasibility study of an extension of the acquaintanceship recruitment
      procedure in recent-onset psychosis.
AB  - The acquaintanceship recruitment procedure is an appealing yet infrequently used
      method to recruit controls, allowing a very close match between patients and
      controls. We used an extension of the acquaintanceship procedure to investigate
      the feasibility of this method to recruit controls in a neuropsychological study
      of recent-onset psychotic patients. Twenty-five recent-onset psychotic patients
      attending a multidisciplinary program devoted to recent-onset psychoses were
      contacted, among whom 13 agreed to participate to the study. At the end of the
      process, only four control participants were assessed. This pilot study suggests
      that several obstacles prevent the use of this procedure to recruit controls in
      this research focusing on recent-onset psychotic disorders.

PMID- 16082302
TI  - Predictors of remission from body dysmorphic disorder: a prospective study.
AB  - In the first naturalistic, prospective study of the course of body dysmorphic
      disorder (BDD), we examined predictors of remission in 161 subjects over 1 year
      of follow-up. Data were obtained on clinical characteristics at the intake
      interview and weekly BDD symptom severity over 1 year using the Longitudinal
      Interval Follow-Up Evaluation. More severe BDD at intake, longer BDD duration,
      and the presence of a comorbid personality disorder predicted a lower likelihood
      of partial or full remission from BDD. BDD remission was not predicted by gender;
      race/ethnicity; socioeconomic status; being an adult versus an adolescent; age of
      BDD onset; delusionality of BDD symptoms; or the presence at intake of major
      depression, a substance use disorder, social phobia, obsessive compulsive
      disorder, or an eating disorder. Receipt of mental health treatment or nonmental
      health treatment (e.g., surgery, dermatologic treatment) during the follow-up
      year also did not predict remission from BDD.

PMID- 16082303
TI  - Endoscopic hemoclip application in the treatment of nonvariceal gastrointestinal
      bleeding: short-term and long-term benefits.
AB  - We conducted an uncontrolled retrospective study to evaluate endoscopic hemoclip
      application as the first-choice hemostatic treatment of gastrointestinal bleeding
      lesions from a wide variety of sources. Clinical data, endoscopic findings,
      complications, and short- and long-term outcomes were also investigated. A total
      of 52 patients (men/women, 36/16; age, 65 +/- 11.5 years) were included in the
      study. Hemoclipping was technically successful in 51 cases (98%). The average
      number of therapeutic endoscopic sessions needed to achieve permanent hemostasis
      was 1.42 +/- 1.2 (range, 1-4). The number of hemoclips required for hemostasis
      depended on the nature of bleeding with the average number of hemoclips used
      being 3.11 +/- 1.12 (range, 2-8). No complications occurred, although 1 patient
      presented recurrent bleeding and was operated on. No further hemorrhage occurred
      during a median follow-up period of 17.32 +/- 5.4 months (range, 2-53).
      Endoscopic hemoclipping provided an effective and safe modality for achieving
      hemostasis in gastrointestinal bleeding from a wide variety of sources, with long
      term benefits.

PMID- 16082304
TI  - Is laparoscopic cholecystectomy cheaper?
AB  - As laparoscopic cholecystectomy is being used more and more frequently, a cost
      analysis was aimed to be performed to evaluate cost effectiveness in Turkey.
      Records of 376 patients who underwent cholecystectomy by various methods were
      analyzed retrospectively. Mean duration of postoperative hospital stay was 5.1 +/
      2.6 days for the open cholecystectomy group (OC group), composed of 177
      patients; 5.6 +/- 2.1 days for the converted open cholecystectomy group (CC
      group) composed of 15 patients; and 2.5 +/- 1.8 days for the laparoscopic
      cholecystectomy group (LC group), which included 184 patients. The mean cost per
      patient was 778 dollars +/- 75, 1964 dollars +/- 82, and 2357 dollars +/- 80 for
      the OC, LC, and CC groups, respectively. It was concluded that laparoscopic
      cholecystectomy will gain economic feasibility over conventional cholecystectomy
      in our country only when costs of laparoscopic equipment lower and personnel
      wages increase sufficiently.

PMID- 16082305
TI  - Value of contrast-enhanced magnetic resonance cholangiography in patients
      undergoing laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy (LC) is the preferred treatment of symptomatic
      gallstone disease. Biliary injury during LC is still a serious problem. Knowledge
      of anatomic detail is important for not encountering the injury. Magnetic
      resonance cholangiography (MRC) is a noninvasive method for imaging the biliary
      ducts. However, MRC has many drawbacks such as not showing anatomic structures in
      detail and respiratory motion. In this study, contrast-enhanced MRC is used to
      show cystic ducts that are not seen by MRC. Reasons for patient referral for MRC
      and contrast-enhanced MRC included suspicion of cholecystolithiasis,
      adenomyomatosis, and gallbladder polyp. Our results show that routine MRC
      revealed cystic ducts in 38 patients (77.5%) and contrast-enhanced MRC in 46
      patients (93.8%). Intraoperative cholangiography (IOC) was taken as gold standard
      for all patients. We found that contrast-enhanced MRC can provide a useful
      supplement to MRC in patients with nonvisualized cystic ducts by MRC. To our
      knowledge, this is the first study of visualization of cystic duct in patients
      undergoing LC depicted by both MRC and contrast-enhanced MRC.

PMID- 16082306
TI  - Percutaneous cholecystostomy using a central venous catheter is effective for
      treating high-risk patients with acute cholecystitis.
AB  - Percutaneous cholecystostomy (PC) using a pigtail catheter is performed on high
      risk patients with acute cholecystitis as their general condition does not
      usually allow them to undergo a "definite" cholecystectomy. However, this method
      of PC is time-consuming and expensive and requires an interventional radiologist
      and specially designed radiologic equipment. To determine whether another PC
      approach was viable, we retrospectively compared patients who underwent PC using
      a central venous catheter (group A, n = 15) with those who underwent standard
      pigtail catheter PC (group B, n = 29). The waiting time prior to undergoing the
      PC was 1.8 days in group A and 3.5 days in group B (P < 0.05). The cost per
      patient was 293,364 won (254.44 dollars) for group A, and 438,719 won (380.50
      dollars) for group B (P < 0.05). There were 4 complications in group A and 5 in
      group B. Following PC, 7 patients in group A and 15 patients in group B underwent
      delayed definite cholecystectomy, and there were no differences between these
      groups in terms of complications, mortality, and the delayed definite
      cholecystectomy surgical method. We conclude that in combination with careful
      patient selection, PC using a central venous catheter in high-risk patients with
      acute cholecystitis is a viable alternative to pigtail catheter PC.

PMID- 16082307
TI  - A powder-free surgical glove bag for retraction of the gallbladder during
      laparoscopic cholecystectomy.
AB  - To test the use of a simple and cheap powder-free glove bag to extract the
      gallbladder during laparoscopic cholecystectomy (LC). The medical records of 142
      consecutive patients who had their gallbladder removed using a powder-free glove
      bag were reviewed. No complications in the form of bile or stone spillage during
      extraction were observed. The absence of complications and the low cost make
      routine use of the glove bag a wise option for extracting the gallbladder during
      LC. The use of the glove bag seems to reduce the risk of contamination with
      bacteria, bile, and gallstones and may reduce contamination by malignant cells in
      case of unexpected gallbladder carcinoma.

PMID- 16082308
TI  - Laparoscopic splenectomy and LigaSure.
AB  - Laparoscopic splenectomy (LS) is a preferred choice, especially for hematologic
      diseases. We present the advantages of the use of LigaSure (energy-based
      equipment that works by applying a precise amount of bipolar energy and pressure
      to the tissue, achieving a permanent seal) for achieving a precise hemostasis,
      thus making the LS easier. We have performed LS using LigaSure on 10 patients (4
      female, 6 male; mean age, 36 years [range, 16-58]) between December 2002 and
      August 2003. All patients had ITP. There were no conversion to open surgery. Mean
      dimensions of spleens were 99 x 49 mm (range, 85 x 36-118 x 60). Intraoperative
      blood loss was no more than 100 mL in any patients (range, 20-100; mean, 60). The
      average operative time was 93 minutes (range, 60-155). There were no
      complications in the postoperative period. The average postoperative stay was 4.3
      days (range, 3-7). LS using LigaSure is a safe and time-sparing procedure with
      almost no complications in this small initial series.

PMID- 16082309
TI  - Hand-assisted laparoscopic radical nephrectomy: comparison of the transperitoneal
      and retroperitoneal approaches.
AB  - Transperitoneal and retroperitoneal approaches have been introduced to perform
      hand-assisted laparoscopic radical nephrectomy. The efficacy and convalescence of
      both approaches were compared. Of 26 patients with renal cell carcinoma, 14
      patients were treated by the transperitoneal approach and 12 by the
      retroperitoneal approach at the same institution. The mean operative time by
      transperitoneal approach was significantly shorter than retroperitoneal approach
      (236.4 and 280.0 minutes, respectively, P < 0.05), but there is a steeper
      learning in retroperitoneal approach. A significant increase in operative time
      was required with an increase in specimen weight (r = 0.591, P < 0.05). There
      were no differences in patient demographic, operative, and convalescence data
      between the both groups. Hand-assisted laparoscopic radical nephrectomy is safe
      by either the transperitoneal or the retroperitoneal approach. Making enough
      retroperitoneal space for the hand and instrument enables us to use the
      retroperitoneal approach readily. Patients with abundant fatty tissues around the
      kidney should be treated by the transperitoneal approach.

PMID- 16082310
TI  - Minilaparotomy for aortoiliac aneurysmal disease: experience and review of the
      literature.
AB  - Vascular surgery is evolving, as other specialities, toward minimally invasive
      techniques. Presently, 3 approaches to aortoiliac disease are suggested as
      minimally invasive. Besides the endovascular procedures, laparoscopic techniques
      and minilaparotomy are being advocated. Although for aneurysmal disease, we favor
      a totally laparoscopic approach, criticisms raised over laparoscopy-assisted
      techniques by those advocating minilaparotomy led us to investigate the benefits
      of the latter technique. We first evaluated the procedure in 7 patients with
      infrarenal abdominal aortic aneurysm (AAA). We found the procedure impossible to
      perform with an 8- to 10-cm incision in 6 of the 7 patients. This led us to
      evaluate causes of failure of the technique. It appeared to us that most of our
      complications were related to inadequate exposure. Fifty consecutive computed
      tomography scans from patients with AAA of surgical size were then reviewed to
      evaluate the aneurysm lengths and compare them to the reported lengths of skin
      incision for minilaparotomy. Results were expressed adding a total of 2 cm for
      proximal and distal clamping. Only 2% of patients would present with aneurysms
      suitable for treatment through an 8-cm midline incision and 30% through a 10-cm
      incision. We then reviewed the literature on minilaparotomy. We believe that
      minilaparotomy should be reserved for those patients with purely aortic disease
      and the appropriate body habitus.

PMID- 16082311
TI  - Laparoscopy-assisted resection of gastric remnant cancer.
AB  - We report a case of gastric remnant carcinoma (GRC) that was successfully treated
      by laparoscopy-assisted gastrectomy. A 69-year-old man was referred to our
      department for management of GRC. Preoperative investigations revealed a slightly
      elevated tumor, 5.0 cm in maximal diameter, confined to the gastric mucosa.
      Computed tomography and endoscopic ultrasonography identified no lymph node
      metastasis. Laparoscopy-assisted gastrectomy was performed including perigastric
      and mesenteric lymph node dissection. The postoperative course was uneventful.
      This is the first reported case of laparoscopically treated GRC. In cases with
      little adhesion from previous surgery, laparoscopic procedure might represent the
      treatment of choice for early GRC in terms of minimal invasiveness.

PMID- 16082312
TI  - Large duodenal villous adenoma requiring head of the pancreas and pylorus
      preserving total duodenectomy.
AB  - Villous adenomas of the duodenum (VAD) are infrequent lesions of the
      gastrointestinal tract but have a high risk of recurrence and malignancy. For
      these reasons and its specific topographic location, the surgical treatment of
      VAD is still controversial. Herein we present a case of large VAD located in the
      second duodenal portion that was successfully treated with a head of the
      pancreas, pylorus-preserving total duodenectomy (PPTD). PPTD should be an
      excellent option in patients with large adenomas because it allows preservation
      of the pancreas, gastrointestinal function is maintained, the possibility of a
      recurrence and of an invasive carcinoma of the ampulla is eliminated, and finally
      because it permits an adequate endoscopic follow-up. PPTD should not be used in
      the presence of malignancy and/or high-grade dysplasia.

PMID- 16082313
TI  - Laparoscopic cholecystectomy in a patient with ankylosing spondylitis with severe
      spinal deformity.
AB  - Laparoscopic cholecystectomy is the current gold standard for the management of
      cholelithiasis. As experience with laparoscopic cholecystectomy has increased,
      contraindications to the procedure have started decreasing. Kyphoscoliosis with
      fixed rigidity is considered as a relative contraindication to laparoscopic
      surgery. Ankylosing spondylitis is a challenge to the anaesthesiologist because
      it is associated with difficult intubation, restrictive ventilatory defects, and
      frequent cardiac involvement. The benefits of laparoscopic surgery can be
      extended to this group of patients with severe kyphoscoliosis due to advances in
      anesthesia and surgical expertise. We report a case of laparoscopic
      cholecystectomy performed in a patient with severe ankylosing spondylitis with
      fixed rigidity of the cervical spine and marked thoracolumbar kyphosis with
      severe restrictive lung disease. The purpose of this report is to describe the
      difficulties encountered in anesthesia and operative difficulties due to altered
      body habitus in terms of patient positioning and surgical access.

PMID- 16082314
TI  - Endoscopic hemoclip placement for postsphincterotomy bleeding refractory to
      injection therapy: report of two cases.
AB  - Bleeding is a serious complication of patients undergoing endoscopic
      sphincterotomy and is the most common sphincterotomy-associated cause of death.
      Two patients presented bleeding after endoscopic sphincterotomy. Despite
      injection treatment with large amounts of epinephrine (1:10,000), the bleeding
      was uncontrolled. Hemostasis was achieved by placing 2 and 3 hemoclips,
      respectively at the bleeding site. Our cases suggest that postsphincterotomy
      bleeding refractory to injection treatment can be safely and effectively
      controlled by endoscopic hemoclipping, thereby avoiding surgery.

PMID- 16082315
TI  - Laparoscopic treatment of an uncommon abdominal localization of Castleman
      disease.
AB  - Castleman disease is a rare lymphoproliferative disorder overall localized in the
      mediastinum and rarely in the abdomen. It appears as a tumor-like mass
      characterized by a massive growth of lymphoid tissue. Benign forms are usually
      associated to a good prognosis even if multifocal variants present more
      aggressive behavior. Two different histologic types have been described: the
      hyaline vascular and the plasma cell form. The diagnosis is often achieved only
      at the histologic evaluation of the surgical specimen. Presented here is the rare
      occurrence of this disease in the abdominal cavity treated by the laparoscopic
      approach. No postoperative complications were observed. No recurrence has been
      detected at 12 months CT scan follow-up. Until now, no reports of this kind of
      treatment have been available in literature.

PMID- 16082316
TI  - Cystic lymphangioma of the small bowel in a woman at 15 weeks' gestation:
      laparoscopic approach.
AB  - Lymphangiomas are uncommon benign tumors, usually encountered early in childhood.
      Here is described the case of a pregnant woman at 15 weeks' gestation with a
      symptomatic ileal small bowel lymphangioma that was approached laparoscopically.
      A limited number of laparoscopically managed cases of abdominal lymphangiomas
      have been reported. This is the first reported laparoscopically assisted
      resection of a small bowel cystic lymphangioma during pregnancy.

PMID- 16082317
TI  - Laparoscopic repair of idiopathic perforation of urinary bladder.
AB  - A 45-year-old man presented with a 10-day history of dysuria and abdominal
      distention. Clinical examination revealed free intraperitoneal fluid and
      tenderness in the lower abdomen. Hematological and biochemical parameters were
      normal except blood urea nitrogen of 76 mg/dL and serum creatinine of 3.4 mg/dL.
      Ultrasonography confirmed moderate ascites with normal-appearing kidneys. In view
      of high creatinine level, normal kidneys, and acute-onset moderate ascites,
      urinary ascites was suspected. A micturating cystogram showed extensive
      intraperitoneal extravasation of the contrast. Cystoscopy identified a 2.5-cm
      perforation on the right side of the dome of the bladder. A laparoscopic closure
      of the perforation was carried out in 2 layers. The histopathology of the excised
      edge showed nonspecific inflammatory changes, and a subsequent urodynamic study
      was normal. The patient remains well 3 years later. This case highlights the
      successful use of laparoscopy in the treatment of a rare urological condition and
      reviews the previously reported cases of laparoscopic closure of bladder
      perforation.

PMID- 16082318
TI  - Robotic resection of an ectopic goiter in the mediastinum.
AB  - We report the first robotic resection of an ectopic mediastinal thyroid adenoma
      in a 72-year-old woman. This intervention was part of staged management for
      excessive bilateral cervical goiter with intrathoracic dispersion. The robotic
      resection was found to be feasible and safe. The robotic operating system offers
      better visual control and operative accuracy than does conventional thoracoscopy.

PMID- 16082319
TI  - Massive subcutaneous emphysema after thoracoscopic argon beamer use for
      pleurodesis.
AB  - Argon beamer coagulation (ABC) has been effectively used in a wide variety of
      thoracoscopic and laparoscopic procedures. However, stringent safety measures
      have to be taken to prevent potentially severe complications due to
      overpressurization. Here we report a case of thoracoscopic pleurodesis with
      talcum powder during which the use of an argon beamer led to severe subcutaneous
      emphysema involving the trunk, upper extremities, neck, and face. Literature on
      complications secondary to the use of ABC in closed body cavities is reviewed.

PMID- 16082320
TI  - Hemorrhage from ruptured hepatic artery pseudoaneurysm co-occurring with
      pancreatic head tumor and portal vein thrombosis: surgical and endovascular
      treatment.
AB  - We report a case of 50-year-old man with a hepatic artery pseudoaneurysm,
      pancreatic head tumor, and portal vein thrombosis. The patient was operated on
      due to acute bleeding into duodenum. The pancreatic tumor was unresectable, which
      is why the ruptured pseudoaneurysm was only sutured. The second therapeutic step
      was to protect the hepatic artery against rupture. Therefore, a stent graft and
      then a wall graft endoprosthesis were placed across the pseudoaneurysm neck. The
      final angiogram demonstrated total exclusion of the pseudoaneurysm with
      preservation of the arterial lumen.

PMID- 16082321
TI  - 2005 immunosuppressive strategies in kidney transplantation: which role for the
      calcineurin inhibitors?
AB  - The calcineurin inhibitors (CNIs) cyclosporine and tacrolimus have been the
      cornerstones of immunosuppressive strategies in clinical transplantation.
      Currently, regimens that are most widely used for induction and maintenance
      therapy include CNIs. However, many clinical trials aiming at reducing or
      eliminating CNIs have been performed in recent years. Here, we review and discuss
      current and future immunosuppressive strategies with a special emphasis on the
      role of CNIs, in the light of recent studies in the field of kidney
      transplantation. In the current era, CNIs still play an important role.

PMID- 16082322
TI  - Heterogeneous alterations in human alloimmunity associated with immunization.
AB  - BACKGROUND: The presence of alloantibodies and/or alloreactive T cells in a
      patient prior to a transplant can impact graft outcome. Environmental factors,
      including therapeutic vaccinations, may influence the strength and/or specificity
      of alloimmunity. METHODS: To address this issue, we prospectively evaluated the
      effects of two different immunization protocols in human subjects on cellular
      alloimmunity using an IFNgamma ELISPOT assay and on alloantibody reactivity by
      flow cytometric analysis of HLA-coated beads. RESULTS: Vaccination/immunization
      was associated with augmentation of cellular and/or humoral alloimmune reactivity
      in >50% of the test subjects. The effects were heterogeneous in that some
      detected increases were transient, peaking 30-60 days postimmunization, whereas
      others persisted for the length of the study. Antibodies reactive to the
      immunizing agent did not cross react with the detected alloantibodies, suggesting
      that the augmentation of alloimmune reactivity was most likely due to a
      nonspecific adjuvant effect from the vaccine. CONCLUSIONS: Therapeutic
      vaccinations can alter the strength of cellular and humoral alloimmunity in
      humans. The results suggest that serial immune monitoring of alloreactivity might
      be beneficial when immunizations are administered to potential transplant
      recipients.

PMID- 16082323
TI  - A prospective, randomized trial of tacrolimus in combination with sirolimus or
      mycophenolate mofetil in kidney transplantation: results at 1 year.
AB  - BACKGROUND: This is the 1-year report of a randomized, multicenter, clinical
      trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with
      tacrolimus-based immunosuppression in kidney transplantation. METHODS: Prior to
      transplantation, recipients were randomized to receive tacrolimus plus
      corticosteroids with either sirolimus (n=185) or MMF (n=176). The incidence of
      biopsy-confirmed acute rejection at 6 months was the primary endpoint of the
      study. Patient and graft survival, renal function, study drug dosing and
      discontinuations were evaluated at 1 year. RESULTS: At 1 year, there was no
      difference in patient survival (95.7% sirolimus vs. 97.2% MMF; P=0.45) or graft
      survival (90.8% sirolimus vs. 94.3% MMF; P=0.22). Patients without delayed graft
      function (DGF) receiving MMF had significantly better graft survival (99% vs.
      93%; P=0.01). Patients receiving a transplant from a live donor had a trend
      towards better graft survival with MMF as compared to sirolimus (98% vs. 91%;
      P=0.07). Patients receiving sirolimus had a significantly higher incidence of
      study drug discontinuation (26.5% vs. 14.8% MMF; P=0.006). Patients receiving MMF
      had significantly better renal function as shown by median serum creatinine
      levels (1.3 mg/dL vs. 1.5 mg/dL; P=0.03) and a trend towards higher calculated
      creatinine clearance (CrCl), (58.4 ml/min vs. 54.3 ml/min; P=0.06). More patients
      in the sirolimus group had a serum creatinine >2.0 mg/dL, (20.4% vs. 11.0%;
      P=0.02). CONCLUSIONS: Tacrolimus is safe and effective in live and deceased donor
      kidney transplantation when given in combination with sirolimus or MMF. Patient
      and graft survival were excellent in both arms. Renal function is superior for
      patients treated with tacrolimus + MMF combination.

PMID- 16082324
TI  - Control of the renal artery and vein with the nonabsorbable polymer ligating clip
      in hand-assisted laparoscopic donor nephrectomy.
AB  - BACKGROUND: The large and variable size of the renal vein has prompted most
      surgeons to select linear stapling devices to secure the vein during laparoscopic
      donor nephrectomy. Although effective, these stapling devices have a potential
      for misfire. Use of the nonabsorbable polymer ligating (NPL) clip during
      laparoscopic donor nephrectomy provides increased graft vessel length compared
      with the stapling device, and the NPL clip has a locking mechanism which may
      increase security compared with standard titanium clips. The objective of this
      study was to evaluate the safety and efficacy of the NPL clip for control of the
      renal artery and vein during hand-assisted laparoscopic donor nephrectomy
      (HALDN). METHODS: A retrospective chart review of 50 consecutive HALDN patients
      was conducted where two parallel NPL clips were used to control both the renal
      artery and vein. Information collected included demographic data, operative and
      postoperative data, and complications. RESULTS: Mean donor age was 33.4 years and
      body mass index was 25.8 kg/m2. Mean operative time was 266.0 min, mean hospital
      stay was 3.2 days, and mean warm ischemia time was 123.3 seconds. There were no
      transfusions, open conversions, or complications related to use of the NPL clip.
      A US 16,300 dollars disposable cost savings was seen during this 1-year period
      alone. CONCLUSIONS: The NPL clip was 100% safe and effective in controlling the
      renal artery and vein during HALDN, allowed for additional vessel length, and
      resulted in a disposable cost savings of US 362 dollars per patient.

PMID- 16082325
TI  - Platelet transfusion containing ABO-incompatible plasma and hepatic veno
      occlusive disease after hematopoietic transplantation in young children.
AB  - BACKGROUND: Hepatic veno-occlusive disease is a major limiting factor of high
      dose chemotherapy in children. The cells lining the hepatic vascular endothelium
      express blood group A and/or B antigens according to the patient's blood group.
      We designed a study evaluating the impact of platelet concentrates containing ABO
      incompatible plasma transfused to young children with a high risk of hepatic veno
      occlusive disease. METHODS: In all, 186 consecutive children (median age: 4
      years, range: 0.75-17 years), treated with high-dose chemotherapy containing
      busulfan followed by hematopoietic stem cell transplantation for neuroblastoma
      (n=112) or brain tumor (n=74) between 1988 and 1998, were investigated. The main
      endpoint was the occurrence of hepatic veno-occlusive disease. Multivariate
      analysis was performed using a Cox's regression model with transfusion of
      platelet concentrates containing ABO-incompatible plasma as a time-dependent
      covariate. RESULTS: We found that 73 out of 186 (39%) children developed hepatic
      veno-occlusive disease after transplantation. Multivariate analysis demonstrated
      that two factors significantly increased the risk of hepatic veno-occlusive
      disease occurrence: transfusion of platelet concentrates containing ABO
      incompatible plasma (P=0.003) and use of melphalan in the conditioning regimen
      (P=0.006). Conversely, the number of platelet concentrates transfusions per week,
      child's age, weight, sex, and use of cyclophosphamide in the conditioning regimen
      had no effect. CONCLUSIONS: Transfusion of platelet concentrates containing ABO
      incompatible plasma increases the risk of hepatic veno-occlusive disease in young
      children treated with a busulfan-containing regimen. Binding of A and/or B
      antigens expressed on the surface of hepatic endothelial cells may promote this
      complication. Transfusion of platelet concentrates containing ABO-incompatible
      plasma should be avoided in these children.

PMID- 16082326
TI  - Hepatitis B core antibody positive donors as a safe and effective therapeutic
      option to increase available organs for lung transplantation.
AB  - BACKGROUND: The use of hepatitis B core antibody (HBcAb+) and hepatitis C
      antibody (HCV Ab+) positive donors represents one strategy to increase available
      donor organs, but this remains controversial because of concern for viral
      transmission to recipients. We hypothesized that isolated HBcAb+ donors represent
      minimal risk of viral transmission in vaccinated lung transplant (LTx)
      recipients. METHODS: A retrospective study was performed of LTx recipients who
      received HBcAb+ or HCV Ab+ pulmonary allografts. We analyzed liver function
      studies, viral hepatitis screening tests, quantitative polymerase chain reaction
      for hepatitis B viral DNA (HBV DNA) and hepatitis C viral RNA (HCV RNA), freedom
      from bronchiolitis obliterans syndrome, acute rejection, and survival. RESULTS:
      Between April 1992 and August 2003, 456 LTx operations were performed. Twenty
      nine patients (HB group) received HBcAb+ allograft transplants with a median
      posttransplant follow-up of 24.5 months. Three critically ill patients (HC group)
      received HCV Ab+ allografts with a median follow-up of 21.5 months. One-year
      survival for the HB group is 83% versus 82% for all patients who received non-HB
      organs (P=0.36). No patient in the HB group developed clinical liver disease
      because of viral hepatitis, and all patients alive (n=21) at follow-up are, to
      date, HBV DNA and/or HBcAb negative. All patients in the HC group tested HCV RNA
      positive; one patient died of liver failure at 22 months. CONCLUSIONS: Risk of
      viral transmission with HCV Ab+ allografts seems high after LTx. However, the use
      of HBcAb+ pulmonary allografts in recipients with prior hepatitis B vaccination
      seems to be a safe and effective strategy to increase organ availability.

PMID- 16082327
TI  - Volume measurement of cerebral blood flow: assessment of cerebral circulatory
      arrest.
AB  - BACKGROUND: Cerebral blood flow (CBF) volume can be measured at bedside by color
      duplex flowmetry of the extracranial cerebral arteries. In neurointensive care
      patients, we prospectively tested the hypothesis that a CBF volume <100 ml/min
      indicates imminent cerebral circulatory arrest. METHODS: CBF volume was
      determined as sum of flow volumes in the internal carotid and vertebral arteries
      of both sides. In 192 neurointensive care patients, 829 measurements were taken.
      When CBF volume fell short of 100 ml/min, common carotid and external carotid
      artery flow volumes were also measured, and transcranial color-coded duplex
      sonography (TCCD) of basal cerebral arteries was performed. Results were compared
      with actual clinical conditions, outcome, and previously published reference
      data. RESULTS: All 41 patients with CBF volume <100 ml/min (range, 0-89 ml/min)
      were officially declared brain dead 2-126 hours after the measurement (median, 23
      hours). TCCD revealed signs of cerebral circulatory arrest in all patients with a
      patent acoustic bone window. External carotid artery flow volumes were normal.
      The lowest CBF volume rate recorded in a surviving patient was 208 ml/min.
      CONCLUSIONS: Early confirmation of cerebral circulatory arrest is of decisive
      importance if the patient is a potential organ donor. CBF volume measurement
      allows confirming the arrest of cerebral circulation even in patients without a
      patent acoustic bone window for TCCD. Because the critical lower threshold for
      survival appears to lie at 200 ml/min, bedside monitoring of CBF volume in
      neurointensive care patients may indicate a therapeutic window before
      irreversible circulatory arrest occurs.

PMID- 16082328
TI  - Impact of statin treatment on 1-year functional and histologic renal allograft
      outcome.
AB  - BACKGROUND: Statins are antilipidemic agents that exhibit a variety of cellular
      effects independent of their lipid-lowering action. A retrospective study was
      undertaken to establish the impact of statins on graft outcome in the first year
      posttransplantation. METHODS: Data from patients with uniform immunosuppression
      (cyclosporine, mycophenolate mofetil, and prednisolone) who underwent
      transplantation at the authors' unit from 1997 to 2002 were reviewed. Patients
      prescribed statins were compared with those not on a statin. Mean change in
      creatinine clearance (CrCl) from 3 to 12 months posttransplantation was
      calculated. Histomorphometric analysis was used to quantify fractional
      interstitial area and collagen III deposition in matched preperfusion and 12
      month protocol biopsy specimens. RESULTS: Seventy-seven patients met study
      criteria: statin, n=44 patients; nonstatin, n=33 patients. Median time to
      commencing a statin was 5 weeks. At 3 months, CrCl (+/-SEM) was similar: 51.6+/
      2.9 mL/min (statin) versus 51.3+/-1 mL/min (nonstatin). At 12 months, the mean
      change in CrCl was 4.1+/-1 mL/min (statin) compared with -2.0+/-1.8 mL/min
      (nonstatin), resulting in a difference of 6.13 mL/min at 12 months (P<0.005).
      Mean preperfusion fractional interstitial areas were similar (23.9+/-1.6%; P=not
      significant [NS]). On 12-month biopsy specimens, the fractional interstitial area
      had increased to 34+/-3.2% in the nonstatin group (P<0.005), with no change in
      the statin group. Interstitial collagen III deposition was similar in
      preperfusion biopsy specimens (10.4+/-1%; P=NS), but at 12 months it was
      significantly greater in the nonstatin group (17.6+/-1%; P<0.05) CONCLUSIONS:
      Early introduction of statins may be associated with improved 1-year graft
      outcome.

PMID- 16082329
TI  - Impact of mode of dialysis on intra-abdominal infection after simultaneous
      pancreas-kidney transplantation.
AB  - BACKGROUND: Whether peritoneal dialysis is a risk factor for the development of
      intra-abdominal infection (IAI) after simultaneous pancreas kidney (SPK)
      transplantation is controversial. METHODS: We investigated the incidence of IAI,
      and patient and pancreas graft survival rates of 120 patients that received SPK
      between November 1995 and August 2003. All patients were dialysis-dependent prior
      to transplantation; mean duration of peritoneal dialysis (PD; n=52) and
      hemodialysis (HD; n=68) was 20+/-15 months and 23+/-16 months, respectively.
      RESULTS: IAI developed in five PD and six HD patients (P=0.88). The time of
      diagnosis of IAI and the spectrum of organisms cultured were similar in the two
      groups of patients. Age, duration of dialysis, and method of exocrine drainage
      did not have a significantly impact on infection rate. Patient and pancreas graft
      survival rates were 92.3% and 88.4% in the PD group and 95.5% and 92% HD group
      (p=ns) after a mean follow-up of 42+/-27 months and 39+/-27 months, respectively.
      Overall patient and pancreas graft survival was not significantly affected by
      IAI. CONCLUSIONS: PD does not adversely affect IAI rate and is a safe mode of
      dialysis for patients awaiting SPK transplantation.

PMID- 16082330
TI  - Terminal sialic acid residues on human glycophorin A are recognized by porcine
      kupffer cells.
AB  - BACKGROUND: We have previously shown that recognition of human erythrocytes by
      porcine Kupffer cells is mediated by a carbohydrate-dependent mechanism. The
      present study explores the possible ligands existing on human glycophorin A and
      tests their ability to inhibit erythrocyte rosette formation. METHODS: Human
      erythrocytes were tested for ABO and MN specificity and used as targets in a
      51Chromium quantitative erythrocyte rosette assay. Monosaccharides present on
      human glycophorin A, neuraminyl lactoses, bovine and porcine submaxillary mucins
      (BSM and PSM), and hyaluronic acid as well as proteoglycan N-linked glycosidase
      F(PNGaseF)- and sialidase A-treated human erythrocyte glycoproteins (hEGP) and
      human erythrocytes were all tested for inhibitory potential in the rosetting
      assay. RESULTS: Porcine Kupffer-cell recognition of human erythrocytes was
      insensitive to differences in blood groups A, B, O, or MN. At 30 mM, the
      monosaccharide, N-acetylneuraminic acid, and the trisaccharide mixture,
      neuraminyl lactoses, disrupted human erythrocyte recognition by 25% and 30%,
      respectively. A dilution of BSM but not PSM inhibited the rosetting assay by 17%
      (.2 mg/mL), 33% (1 mg/mL), and 53% (2 mg/mL). The same dilution of hyaluronic
      acid had no effect on rosetting. Removal of N-linked oligosaccharides from hEGP
      with PNGaseF did not impair its ability to inhibit the rosetting assay. In
      contrast, removal of sialic acid completely abrogated its inhibitory ability.
      Treatment of whole human erythrocytes with sialidase A likewise prevented
      recognition by porcine Kupffer cells. CONCLUSIONS: Terminal sialic acid on human
      erythrocytes is a target recognized by porcine Kupffer cells, suggesting a role
      for a sialic-acid receptor in innate cellular recognition of xenogeneic epitopes.
      Inasmuch as this work reveals a carbohydrate-recognition mechanism for cellular
      rejection, we shed light on a potential new boundary that will need to be
      overcome within xenotransplantation.

PMID- 16082331
TI  - Beyond operational tolerance: effect of ischemic injury on development of chronic
      damage in renal grafts.
AB  - BACKGROUND: The induction of operational tolerance is the holy grail of clinical
      transplantation. However, in animal models with operational tolerance, long- term
      grafts still develop chronic damage. The elucidation of the impact of allogenic
      versus nonallogeneic factors in such a model is important. This study examined
      the effect of a clinically relevant combination of warm ischemia and cold
      preservation in the absence of allogeneic response (isografts) and in the context
      of operational tolerance. METHODS: Dark Agouti (DA) rat kidneys were transplanted
      into DA recipients (isografts) or Albino Surgery recipients (allografts)
      tolerized by two transfusions of DA blood, under cover of cyclosporin A. Grafts
      were subjected to minimal cold preservation or to 30 mins warm ischemia followed
      by 24 hrs cold preservation. RESULTS: After an initial peak of renal dysfunction,
      serum creatinine concentration returned to normal in isografts and nonischemic
      allografts, but remained significantly elevated in ischemic allografts (P<0.0002)
      throughout 6 months follow-up. Both allograft groups developed proteinuria. At 6
      months, ischemic isografts and nonischemic allografts demonstrated very mild
      tubular atrophy and interstitial fibrosis. Tubulointerstitial injury was
      significantly more severe in ischemic allografts (P<0.01 vs. nonischemic
      allografts) and was associated with increased infiltrating monocyte/macrophages
      and NK cells (P<0.05). Moderate glomerulosclerosis was a feature of both
      allograft groups (P<0.05). CONCLUSIONS: The modified allogeneic response in
      operationally tolerant recipients acts in synergy with ischemia/reperfusion
      injury in the development of chronic damage. Strategies to limit or modify the
      initial ischemia/reperfusion injury may ameliorate chronic tubulointerstitial
      damage. Progressive glomerular damage and proteinuria in allografts may require
      other pharmacological intervention.

PMID- 16082332
TI  - Tolerance by selective in vivo expansion of foreign major histocompatibility
      complex-transduced autologous bone marrow.
AB  - BACKGROUND: Application of gene therapy to induce antigen-specific immune
      tolerance could be important for transplantation or treatment of autoimmune
      diseases. Hematopoietic stem cell-based gene therapy has been hampered by
      relatively weak gene expression in vivo and loss of transduced cells over time.
      Selective expansion of transduced hematopoietic stem cells has been accomplished
      by incorporating the dihydrofolate reductase (DHFR) gene into the gene transfer
      vector. METHODS: To assess whether this strategy could be applied to
      transplantation, we constructed a retroviral vector plasmid (KA274) containing
      the cDNA encoding human leukocyte antigen (HLA)-A2.1 and a tyr22 mutant DHFR and
      generated vesicular stomatitis virus-G-pseudotyped recombinant retrovirus by
      transfection into 293GPG cells. Bone marrow cells from C57BL/6 mice were infected
      with KA274 at a multiplicity of infection of 100, and transplanted into lethally
      irradiated syngeneic mice. RESULTS: After transplantation with transduced bone
      marrow, the proportion of peripheral blood cells expressing HLA-A2 ranged from
      3.2% to 38% and increased 2- to 4.9-fold after selection for DHFR-expressing
      cells using trimetrexate and nitrobenzylmercaptpurine riboside 5' monophosphate.
      HLA-A2 expression remained above pretreatment levels throughout the study.
      Cytotoxic spleen cells from reconstituted mice lysed third-party HLA-B7
      expressing targets but were unable to lyse HLA-A2-expressing targets. All KA274
      reconstituted C57BL/6 mice accepted skin grafts from HLA-A2.1 transgenic mice for
      more than 245 days but rejected third-party Balb/c skin grafts in 12 days.
      CONCLUSION: Long-term transgene expression and immunologic tolerance to
      retrovirus-encoded HLA-A2, equivalent to that obtained by donor bone marrow
      transplantation, was accomplished, and selective expansion of transduced bone
      marrow cells was induced using DHFR as a selectable marker.

PMID- 16082333
TI  - Robust tolerance to fully allogeneic islet transplants achieved by chimerism with
      minimal conditioning.
AB  - BACKGROUND: Whether mixed chimeras induced by nonmyeloablative conditioning are
      tolerant to challenge with donor allogeneic islet grafts is unknown. Here we
      investigate whether our nonmyeloablative, costimulation blockade-free and
      sirolimus (SRL)-based protocol could facilitate mixed chimerism via bone marrow
      transplantation (BMT) and induce islet allograft tolerance. METHODS: After low
      dose (1-3 Gy) total body irradiation (TBI, day -1), with or without prior
      lymphocyte depletion, C57BL/6 mice were transfused with 40 x 10(6) BALB/c bone
      marrow cells (day 0) and received SRL (3 mg/kg/day) for 4 weeks. Chimerism was
      monitored by flow cytometry and the recipients were rendered diabetic chemically
      and challenged with donor islets. RESULTS: Mixed chimerism was achieved in mice
      treated with TBI 3 Gy/SRL but it declined over time in 60% (9/15) of them. Long
      term stable chimerism was established in 100% of recipients over 50 weeks with
      either antilymphocyte serum (ALS, 9/9), anti-CD4 (4/4), or anti-CD4 plus anti-CD8
      (5/5) prior to BMT. TBI conditioning could be reduced to 1 Gy, with 90% (9/10)
      maintaining chimerism in the long-term. When TBI was substituted with
      cyclophosphamide (CTX) or busulfan (BUS), all mice remained chimeric in the long
      term. The chimeras showed no proliferative response to donor antigen and accepted
      both first and second donor-specific islet grafts indefinitely while rejecting
      third-party grafts. CONCLUSIONS: This data provides the first evidence that
      stable fully allogeneic chimeras induced with BMT after nonmyeloablative
      conditioning with SRL and lymphocyte-depleting antibodies exhibit robust donor
      specific tolerance to islet grafts.

PMID- 16082334
TI  - A novel small-molecule compound targeting CCR5 and CXCR3 prevents acute and
      chronic allograft rejection.
AB  - BACKGROUND: Chemokines and chemokine receptors are critical in leukocyte
      recruitment, activation, and differentiation. Among them, CC chemokine receptor 5
      (CCR5) and CXC chemokine receptor 3 (CXCR3) have been reported to play important
      roles in alloimmune responses and may be potential targets for posttransplant
      immunosuppression. METHODS: Fully major histocompatibility complex (MHC)
      mismatched murine cardiac and islet transplant models were used to test the
      effect in vivo of a novel, small-molecule compound TAK-779 by targeting CCR5 and
      CXCR3 in acute allograft rejection. An MHC class II mismatched cardiac transplant
      model was used to evaluate its efficacy in chronic allograft rejection.
      Intragraft expression of cytokines, chemokines, and chemokine receptors was
      measured by quantitative real-time polymerase chain reaction and by histological
      analysis. RESULTS: Treatment of TAK-779 significantly prolonged allograft
      survival across the MHC barrier in two distinct transplant models. The treatment
      downregulated local immune activation as observed by the reduced expression of
      several chemokines, cytokines, and chemokine receptors. Thereby, the recruitment
      of CD4, CD8, and CD11c cells into transplanted allografts were inhibited.
      Furthermore, TAK-779 treatment significantly attenuated the development of
      chronic vasculopathy, fibrosis, and cellular infiltration. CONCLUSIONS:
      Antagonism of CCR5 and CXCR3 has a substantial therapeutic effect on inhibiting
      both acute and chronic allograft rejection. CCR5 and CXCR3 are functional in the
      process of allograft rejection and may be potential targets in clinical
      transplantation in the future.

PMID- 16082335
TI  - The autoimmune response to vimentin after renal transplantation in nonhuman
      primates is immunosuppression dependent.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) is a common late complication of
      kidney transplantation. Antibodies to both human leukocyte antigen and nonhuman
      leukocyte antigen antigens have been implicated in the development of this
      condition. Here we investigated the presence of antivimentin antibodies in
      nonhuman primate recipients of kidney allografts as a possible predictor of CAN
      and the effects of immunosuppression. METHODS: Thirty seven rhesus monkeys
      received a kidney allograft to study the potency of several different
      immunosuppressive regimens (conventional immunosuppression, n=19, vs.
      costimulatory blockade, n=18). Monkeys were tested for antivimentin antibody by
      enzyme-linked immunosorbent assay and for anti-donor antibody by staining donor
      spleen cells with recipient serum. The appearance of antibodies was correlated
      with the graft pathology in biopsy and necropsy material. RESULTS: Antivimentin
      antibodies were found in 31 of 37 animals, whereas only 15 of 32 animals made
      anti-donor antibodies. Conventional immunosuppression did not prevent
      antivimentin antibody formation. Costimulation blockade, in particular blocking
      CD40 and CD86, significantly delayed or prevented antivimentin antibody
      formation, but did not prevent CAN. Antivimentin antibodies were not
      significantly associated with development of CAN. CONCLUSIONS: We postulate that
      vimentin acts as an autoantigen after renal transplantation; it elicits an
      autoimmune response that is not regulated by cyclosporine. This autoimmune
      response may be part of the complex immunologic events occurring
      posttransplantation and may contribute to the development of CAN, but cannot be
      considered as a major cause of CAN because this condition also develops without
      antivimentin antibodies.

PMID- 16082336
TI  - Decreased alloreactivity using donor cells from mice expressing a CD200 transgene
      under control of a tetracycline-inducible promoter.
AB  - BACKGROUND: CD200 delivers an immunsuppressive signal that augments allograft
      survival following interaction with its receptor, CD200R1. We hypothesized that
      mice overexpressing CD200 as a trangene would also show a diminished
      alloresponsiveness and decreased allograft rejection. METHODS: A transgenic mouse
      on a C57BL/6 background, expressing a murine CD200 cDNA genetically linked to a
      green fluorescent protein tag (GFP) under control of a tetracycline response
      element (TRE), was mated with a commercial transgenic mouse carrying the reverse
      tetracycline regulated transactivator gene under control of a human CMV promoter.
      F1 mice were examined for induction of alloimmunity in vivo/in vitro, and for
      their ability to reject skin allografts in vivo. RESULTS: The F1 hybrid expressed
      CD200 after exposure to doxycyline (DOX), as assessed both by enhanced GFP
      expression in multiple organs and CD200-GFP expression. Splenocytes from F1 mice
      stimulated with LPS or allogeneic cells in vitro in the presence/absence of DOX
      showed reduced production of TNFalpha, and of allospecific CTL. Splenocytes from
      F1 mice used as stimulator cells in allogeneic MLCs in the presence of DOX were
      inefficient at induction of cytokines or CTL in vitro from normal allogeneic
      responder cells. Skin grafts from transgenic mice were inefficient at induction
      of CTL in vivo. Transgenic mice receiving DOX showed prolonged acceptance of skin
      allografts, which was abolished by infusion of anti-CD200 mAb. CONCLUSIONS: Our
      data confirmed that overexpression of CD200 in transgenic mice, or in skin grafts
      from these mice, decreases alloimmunity. This has potential clinical utility in
      transplantation and other diseases.

PMID- 16082337
TI  - Rapid destruction of encapsulated islet xenografts by NOD mice is CD4-dependent
      and facilitated by B-cells: innate immunity and autoimmunity do not play
      significant roles.
AB  - BACKGROUND: Spontaneously diabetic NOD mice rapidly reject microencapsulated
      islet xenografts via an intense pericapsular inflammatory response. METHODS:
      Tilapia (fish) islets were encapsulated in 1.5% alginate gel microspheres.
      Recipients in series 1 were spontaneously diabetic NOD mice and streptozotocin
      diabetic nude, euthymic Balb/c, prediabetic NOD, and NOR (a recombinant congenic
      strain not prone to autoimmune diabetes) mice. Recipients in Series 2 were STZ
      diabetic NOD, NOD-scid, NOD CD4 T-cell KO, NOD CD8 T-cell KO, and NOD B-cell KO
      mice. RESULTS: In Series 1, encapsulated fish islet grafts uniformly survived
      long-term in nude mice but were rejected in Balb/c and, at a markedly accelerated
      rate, in spontaneously diabetic NOD, streptozotocin-diabetic NOD and NOR
      recipients. Histologically, intense inflammation (macrophages and eosinophils)
      surrounding the microcapsules was seen only in NOD and NOR recipients. In Series
      2, encapsulated fish islets uniformly survived long-term in NOD-scid and NOD CD4
      KO mice; graft survival was markedly prolonged in B-cell KO (P<0.001) but not CD8
      KO mice. CONCLUSIONS: The rapid rejection of alginate encapsulated islet
      xenografts by NOD mice is not solely a consequence of beta-cell directed
      autoimmunity nor is it merely a vigorous innate immune response. Graft rejection
      requires CD4 T-cells, is facilitated by B-cells, and does not require CD8 T
      cells.

PMID- 16082338
TI  - A rapid test to monitor alloreactive responses in whole blood using real-time
      polymerase chain reaction.
AB  - Rapid, simple, and reliable assays to monitor allogeneic responses are essential
      for the safe development of novel protocols of tailored immunosuppression.
      Herein, we describe a real-time polymerase chain reaction method based on
      interleukin-2 and interferon-gamma mRNA quantification upon stimulation of whole
      blood with allogeneic T cell-depleted peripheral blood mononuclear cells. The
      technique requires only small blood volumes and results can be obtained within 48
      hours. Data obtained in a liver transplant patient receiving a tolerance
      induction protocol based on the infusion of donor-type hematopoietic stem cells
      suggest that this rapid whole blood mixed lymphocyte reaction assay could be
      valuable for the monitoring of patients undergoing solid organ or hematopoietic
      stem cell transplantation.

PMID- 16082339
TI  - Two-year reduction of panel reactive human leukocyte antigen antibodies in
      children receiving mycophenolate mofetil after valved allograft placement.
AB  - Allografts used in the repair of congenital heart defects in children induce a
      persistent broad HLA antibody response. We have previously shown that a 3-month
      course of mycophenolic mofetil (MMF) significantly reduces the HLA class I
      antibody response to valved allograft implantation in children. The purpose of
      this study was to determine if this reduction in HLA antibody persists after
      discontinuation of MMF. We conducted follow-up (mean 2 +/- 0.5 years) of seven
      patients who had received allograft placement for repair of congenital heart
      defects. These patients received 3 months of immunosuppression with MMF following
      allograft implantation. When compared to historical controls, patients who
      received MMF following surgery showed a significantly decreased HLA class I
      antibody response at 2 years postimplantation. This study demonstrates the
      ability to persistently alter the HLA class I antibody response using 3 months of
      MMF following allograft implantation in children.

PMID- 16082340
TI  - Characterizing lung metabolism with carbon-13 magnetic resonance spectroscopy in
      a small-animal model: evidence of gluconeogenesis during hypothermic storage.
AB  - Experimental evidence suggests storing lungs inflated with oxygen and with
      oxidizable substrate improves results of lung transplantation. Glucose is
      included in the low-potassium-dextran (LPD) solution Perfadex to achieve this
      goal. The authors hypothesized that other substrates might be more effective. Rat
      lungs were stored for 6 or 24 hr in LPD solution with the following carbon-13-
      labeled substrates: 5 mM glucose (Perfadex group), 32 mM pyruvate (pyruvate
      group), or both (combination group). Metabolism was assessed by magnetic
      resonance spectroscopy. Small amounts of exogenous glucose were oxidized in the
      Perfadex group. In contrast, exogenous pyruvate was the major substrate oxidized
      in the pyruvate and combination groups (P<0.01 vs. Perfadex). Carbon-13--labeled
      glucose and glycogen were detected in the pyruvate group, suggesting that
      gluconeogenesis and glycogen synthesis occur in glucose-deprived lungs. Lungs for
      transplantation metabolize substrates through both anabolic and catabolic
      pathways. These reactions may be important in designing improved solutions for
      lung preservation.

PMID- 16082342
TI  - Renal replacement therapy after liver transplantation.

PMID- 16082341
TI  - Cadaveric orthotopic auxiliary split liver transplantation and kidney
      transplantation: an alternative for type 1 primary hyperoxaluria.
AB  - Liver transplantation (LTX) corrects the enzymatic defect responsible for type 1
      primary hyperoxaluria (PH1). It has been advocated in combination with kidney
      transplantation (KTX) in patients with renal failure from PH1 because KTX alone
      can result in early graft loss. A 58-year-old male patient with PH1 on
      hemodialysis underwent resection of the left lateral segment of the liver
      followed by orthotopic auxiliary left lateral segment liver transplantation and
      kidney transplantation from a deceased donor. The serum oxalate dropped from 34.8
      micromol/L before transplant to 3.6-8.3 in the first months posttransplant to <1
      micromol/L (normal range 0.4-3.0). One year after posttransplant, the patient has
      an iothalamate glomerular filtration rate of 58 ml/min. Orthotopic auxiliary LTX
      is an alternative to whole LTX in PH1. By using a split deceased donor liver, it
      does not deprive the donor pool and protects the recipient from liver failure in
      case of graft loss.

PMID- 16082344
TI  - Syngeneic vs. allotransplantation in chronic myeloid leukemia: all's well that
      ends well.

PMID- 16082345
TI  - Illuminating BiDil.

PMID- 16082346
TI  - US biosecurity advisory board faces delicate balancing act.

PMID- 16082347
TI  - Next-generation monoclonals less profitable than trailblazers?

PMID- 16082348
TI  - Japan-China merger puts growth in East Asia first.

PMID- 16082349
TI  - Malaysia tiptoes on the heels of Asian neighbors.

PMID- 16082351
TI  - Profile: William Haseltine.

PMID- 16082352
TI  - Enthusiasm cools in Q2.

PMID- 16082353
TI  - The zinc finger nuclease monopoly.

PMID- 16082354
TI  - The Babel of genetic data terminology.

PMID- 16082355
TI  - Will Bt cotton remain effective in India?

PMID- 16082356
TI  - Whose tissue is it anyway?

PMID- 16082357
TI  - No pain, no gain?

PMID- 16082359
TI  - Patent pools and standard setting in diagnostic genetics.

PMID- 16082360
TI  - Recent patent applications in systems biology.

PMID- 16082361
TI  - Closing the circle of osmoregulation.

PMID- 16082362
TI  - Discovering DNA regulatory elements with bacteria.

PMID- 16082363
TI  - Hot spot MRI emerges from the background.

PMID- 16082364
TI  - siRNA becomes smart and intelligent.

PMID- 16082366
TI  - Probabilistic model of the human protein-protein interaction network.
AB  - A catalog of all human protein-protein interactions would provide scientists with
      a framework to study protein deregulation in complex diseases such as cancer.
      Here we demonstrate that a probabilistic analysis integrating model organism
      interactome data, protein domain data, genome-wide gene expression data and
      functional annotation data predicts nearly 40,000 protein-protein interactions in
      humans-a result comparable to those obtained with experimental and computational
      approaches in model organisms. We validated the accuracy of the predictive model
      on an independent test set of known interactions and also experimentally
      confirmed two predicted interactions relevant to human cancer, implicating
      uncharacterized proteins into definitive pathways. We also applied the human
      interactome network to cancer genomics data and identified several interaction
      subnetworks activated in cancer. This integrative analysis provides a
      comprehensive framework for exploring the human protein interaction network.

PMID- 16082367
TI  - Using process diagrams for the graphical representation of biological networks.
AB  - With the increased interest in understanding biological networks, such as protein
      protein interaction networks and gene regulatory networks, methods for
      representing and communicating such networks in both human- and machine-readable
      form have become increasingly important. Although there has been significant
      progress in machine-readable representation of networks, as exemplified by the
      Systems Biology Mark-up Language (SBML) (http://www.sbml.org) issues in human
      readable representation have been largely ignored. This article discusses human
      readable diagrammatic representations and proposes a set of notations that
      enhances the formality and richness of the information represented. The process
      diagram is a fully state transition-based diagram that can be translated into
      machine-readable forms such as SBML in a straightforward way. It is supported by
      CellDesigner, a diagrammatic network editing software
      (http://www.celldesigner.org/), and has been used to represent a variety of
      networks of various sizes (from only a few components to several hundred
      components).

PMID- 16082368
TI  - Gene targeting using zinc finger nucleases.
AB  - The ability to achieve site-specific manipulation of the mammalian genome has
      widespread implications for basic and applied research. Gene targeting is a
      process in which a DNA molecule introduced into a cell replaces the corresponding
      chromosomal segment by homologous recombination, and thus presents a precise way
      to manipulate the genome. In the past, the application of gene targeting to
      mammalian cells has been limited by its low efficiency. Zinc finger nucleases
      (ZFNs) show promise in improving the efficiency of gene targeting by introducing
      DNA double-strand breaks in target genes, which then stimulate the cell's
      endogenous homologous recombination machinery. Recent results have shown that
      ZFNs can be used to create targeting frequencies of up to 20% in a human disease
      causing gene. Future work will be needed to translate these in vitro findings to
      in vivo applications and to determine whether zinc finger nucleases create
      undesired genomic instability.

PMID- 16082375
TI  - Golden opportunities.

PMID- 16082377
TI  - Rapid and efficient nonviral gene delivery of CD154 to primary chronic
      lymphocytic leukemia cells.
AB  - Interactions between CD40 and CD40 ligand (CD154) are essential in the regulation
      of both humoral and cellular immune responses. Forced expression of human CD154
      in B chronic lymphocytic leukemia (B-CLL) cells can upregulate costimulatory and
      adhesion molecules and restore antigen-presenting capacity. Unfortunately, B-CLL
      cells are resistant to direct gene manipulation with most currently available
      gene transfer systems. In this report, we describe the use of a nonviral,
      clinical-grade, electroporation-based gene delivery system and a standard plasmid
      carrying CD154 cDNA, which achieved efficient (64+/-15%) and rapid (within 3 h)
      transfection of primary B-CLL cells. Consistent results were obtained from
      multiple human donors. Transfection of CD154 was functional in that it led to
      upregulated expression of CD80, CD86, ICAM-I and MHC class II (HLA-DR) on the B
      CLL cells and induction of allogeneic immune responses in MLR assays.
      Furthermore, sustained transgene expression was demonstrated in long-term
      cryopreserved transfected cells. This simple and rapid gene delivery technology
      has been validated under the current Good Manufacturing Practice conditions, and
      multiple doses of CD154-expressing cells were prepared for CLL patients from one
      DNA transfection. Vaccination strategies using autologous tumor cells manipulated
      ex vivo for patients with B-CLL and perhaps with other hematopoietic malignancies
      could be practically implemented using this rapid and efficient nonviral gene
      delivery system.

PMID- 16082378
TI  - Ionizing radiation: a genetic switch for cancer therapy.
AB  - Gene therapy of cancer represents a promising but challenging area of therapeutic
      research. The discovery of radiation-inducible genes led to the concept and
      development of radiation-targeted gene therapy. In this approach, promoters of
      radiation-inducible genes are used to drive transcription of transgenes in the
      response to radiation. Constructs in which the radiation-inducible promoter
      elements activate a transgene encoding a cytotoxic protein are delivered to
      tumors by adenoviral vectors. The tumoricidal effects are then localized
      temporally and spatially by X-rays. We review the conceptual development of
      TNFerade, an adenoviral vector containing radiation-inducible elements of the
      early growth response-1 promoter upstream of a cDNA encoding human tumor necrosis
      factor-alpha. We also summarize the preclinical work and clinical trials
      utilizing this vector as a treatment for diverse solid tumors.

PMID- 16082379
TI  - Combination of cytosine deaminase suicide gene expression with DR5 antibody
      treatment increases cancer cell cytotoxicity.
AB  - Combined treatment using adenoviral-directed enzyme/prodrug therapy and
      immunotherapy has the potential to become a powerful alternative method of cancer
      therapy. We have developed adenoviral vectors encoding the cytosine deaminase
      gene (Ad-CD) and cytosine deaminase:uracil phosphoribosyltransferase fusion gene
      (Ad-CD:UPRT). A monoclonal antibody, TRA-8, specifically binds to death receptor
      5, one of two death receptors bound by tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL). The purpose of this study was to evaluate cytotoxicity
      in vitro and therapeutic efficacy in vivo of the combination of Ad-CD:UPRT and
      TRA-8 against human pancreatic cancer and glioma cell lines. The present study
      demonstrates that Ad-CD:UPRT infection resulted in increased 5-FC-mediated cell
      killing, compared with Ad-CD. Furthermore, a significant increase of cytotoxicity
      following Ad-CD:UPRT/5-FC and TRA-8 treatment of cancer cells in vitro was
      demonstrated. Animal studies showed significant inhibition of tumor growth of MIA
      PaCa-2 pancreatic and D54MG glioma xenografts by the combination of Ad-CD:UPRT/5
      FC plus TRA-8 as compared with either agent alone or no treatment. The results
      suggest that the combination of Ad-CD:UPRT/5-FC with TRA-8 produces an additive
      cytotoxic effect in cancer cells in vitro and in vivo. These data indicate that
      combined treatment with enzyme/prodrug therapy and TRAIL immunotherapy provides a
      promising approach for cancer therapy.

PMID- 16082380
TI  - Suppressor of cytokine signaling-1 expression by infectivity-enhanced adenoviral
      vector inhibits IL-6-dependent proliferation of multiple myeloma cells.
AB  - Multiple myeloma (MM) accounts for 10% of hematological malignant disorders. Its
      refractory nature indicates the necessity of developing novel therapeutic
      modalities. Since interleukin 6 (IL-6) is one of the major growth factors for MM
      cells, we expressed suppressor of cytokine signaling-1 (SOCS-1), one of the
      blockades of IL-6 receptor downstream signaling, to suppress the proliferation of
      MM cells. Because MM cells are resistant to conventional adenoviral vector
      infection, we utilized infectivity-enhanced adenoviral vectors with an RGD4C
      motif in the adenoviral fiber-knob region (RGD-modified vector). In infectivity
      analysis, RGD-modified vectors were superior to unmodified controls in the
      majority of the MM cell lines tested. The overexpression of SOCS-1 using
      infectivity-enhanced adenoviral vectors achieved growth suppression in IL-6
      dependent MM cells, but not in the IL-6-independent cells. IL-6-induced STAT3
      phosphorylation was suppressed in IL-6-dependent cells, indicating that the
      signal transduction cascade of the IL-6 receptor signaling was blocked. In
      aggregate, SOCS-1 overexpression with RGD-modified adenoviral vectors achieved
      the antiproliferative effect in IL-6-dependent MM cells. These results provide an
      initial proof-of-principle of the anticancer effect of SOCS-1 expression vector
      as well as a promise for the future development of therapeutic modality for MM
      based on this vector.

PMID- 16082381
TI  - Biological activities of a recombinant adenovirus p53 (SCH 58500) administered by
      hepatic arterial infusion in a Phase 1 colorectal cancer trial.
AB  - The major focus of intrahepatic arterial (IHA) administration of adenoviruses
      (Ad) has been on safety. Currently, there is little published data on the
      biological responses to Ad when administered via this route. As part of a Phase I
      study, we evaluated biological responses to a replication-defective adenovirus
      encoding the p53 transgene (SCH 58500) when administered by hepatic arterial
      infusion to patients with primarily colorectal cancer metastatic to the liver. In
      analyzing biological responses to the Ad vector, we found that both total and
      neutralizing Ad antibodies increased weeks after SCH 58500 infusion. The fold
      increase in antibody titers was not dependent on SCH 58500 dosage. The
      proinflammatory cytokine interleukin-6 (IL-6) transiently peaked within 6 h of
      dosing. The cytokine sTNF-R2 showed elevation by 24 h post-treatment, and fold
      increases were directly related to SCH 58500 doses. Cytokines TNF-alpha, IL
      1beta, and sTNF-R1 showed no increased levels over 24 h. Predose antibody levels
      did not appear to predict transduction, nor did serum Ad neutralizing factor
      (SNF). Delivery of SCH 58500 to tumor tissue occurred, though we found
      distribution more predominantly in liver tissues, as opposed to tumors. RT-PCR
      showed significantly higher expression levels (P<0.0001, ANOVA) for adenovirus
      type 2 and 5 receptor (CAR) in liver tissues, suggesting a correlation with
      transduction. Evidence of tumor-specific apoptotic activity was provided by laser
      scanning cytometry, which determined a coincidence of elevated nuclear p53
      protein expression with apoptosis in patient tissue. IHA administration of a
      replication defective adenovirus is a feasible mode of delivery, allowing for
      exogenous transfer of the p53 gene into target tissues, with evidence of
      functional p53. Limited and transient inflammatory responses to the drug
      occurred, but pre-existing immunity to Ad did not preclude SCH 58500 delivery.

PMID- 16082382
TI  - Comparative studies of suppression of malignant cancer cell phenotype by
      antisense oligo DNA and small interfering RNA.
AB  - One of the distinguishing features of malignant tumor cells is the ability to
      proliferate in an anchorage-independent manner; methods that effectively suppress
      this phenotype may be applicable to the therapeutic inhibition of the malignancy
      of cancers. Interfering RNA is a potentially powerful tool for cancer therapy
      because of its specificity of target selection and remarkably high efficiency in
      target mRNA suppression. We studied the use of two knockdown strategies,
      antisense oligo DNA (AS-ODN) and small interfering RNA (siRNA), and showed how
      the anchorage-independent proliferation of malignant cells could be blocked
      efficiently. Anchorage-independent proliferation of rat fibroblasts transformed
      with v-src was suppressed with only a single 1-microM dose of AS-ODN; similar
      suppression using siRNA required treatment with 1 nM siRNA every 12 h. With our
      experimental system, the molecular stability of AS-ODN allowed the use of a
      simple treatment regimen to control the amount of the target molecule, providing
      that the treatment dose was sufficiently high. In comparison, siRNA treatment was
      effective at lower doses, but more frequent treatment was necessary to achieve
      the same suppression of proliferation.

PMID- 16082383
TI  - A tumor-specific conditionally replicative adenovirus vector expressing TRAIL for
      gene therapy of hepatocellular carcinoma.
AB  - We constructed a novel hepatocellular carcinoma-specific conditionally
      replicative adenovirus (CRAd). This adenovirus, designated Ad.HS4.AFP.E1A/TRAIL,
      expresses E1A to mediate viral replication and TRAIL to enhance HCC-killing
      efficacy under the control of a modified AFP promoter. An insulator HS-4 was
      placed in front of the AFP promoter to enhance the fidelity of the heterologous
      promoter. This virus was shown to have specific cytolytic activity in AFP
      expressing HCC cells in vitro. Furthermore, the replication efficiency of
      Ad.HS4.AFP.E1A/TRAIL correlated well with AFP expression of the host cells,
      showing a 100-fold and 1 000 000-fold decrease in the low-and non-AFP-expressing
      HCC cells, respectively, compared to the high AFP-expressing HCC cells. An
      increase in mRNA of TRAIL and the elevated Caspase-3 activity were also observed
      in Ad.HS4.AFP.E1A/TRAIL-infected HCC cells. These results indicated that TRAIL
      expression from the viral vector activated the Caspase-3 enzymatic capacity and
      the HCC cells were sensitive to TRAIL. In vivo, Ad.HS4.AFP.E1A/TRAIL effectively
      prevented the growth of low AFP-expressing BEL-7404 xenografts. These results
      indicate that Ad.HS4.AFP.E1A/TRAIL could provide a new strategy of gene therapy
      for HCC.

PMID- 16082384
TI  - Efficacy of a single intravesical treatment with Ad-IFN/Syn 3 is dependent on
      dose and urine IFN concentration obtained: implications for clinical
      investigation.
AB  - There is a need to improve the treatment of superficial bladder cancer. One area
      which holds promise is intravesical gene therapy. Recently, studies undertaken by
      us have shown that marked tumor regression of bladder cancers occurred after two
      daily intravesical administrations of an adenovirus encoding human interferon
      alpha (Ad-IFNalpha) using a mouse superficial bladder cancer model in which human
      bladder tumors are growing. A dose of 1 x 10(11) particles/ml (P/ml) was used
      along with 1 mg/ml of Syn3, a gene transfer-enhancing agent. Since clinical
      studies are being planned using this approach, it became critical to determine if
      one exposure and lower particle number could be equally effective. We report that
      indeed a single dose of Ad-IFNalpha in Syn3 at doses of 1 x 10(10)-1 x 10(11)
      P/ml is highly effective in reducing the size of the tumors, whereas 1 x 10(9)
      P/ml was not. Efficacy was also correlated with the level of IFN produced in the
      urine after treatment. Based on the results of the present studies, a Phase I
      trial is being planned for superficial bladder cancer, which will involve a
      single initial treatment with Ad-IFNalpha/Syn3 and measurement of IFN in the
      urine over time as an indicator of adequate gene transfer and expression.

PMID- 16082385
TI  - The transcription factor GATA2 regulates differentiation of brown adipocytes.
AB  - Brown adipose tissue (BAT) is a specialized mammalian tissue and a site of
      adaptive thermogenesis. Although the metabolic functions of brown and white
      adipocytes are distinct, terminal differentiation of both adipocyte lineages is
      regulated by well-characterized common transcription factors. However, the early
      stages of adipocyte differentiation and regulation of precursor cells are not
      well understood. We report here that GATA2 is expressed in brown adipocyte
      precursors, and its expression is downregulated in a differentiation-dependent
      manner. Constitutive expression of GATA2 suppressed expression of BAT-specific
      genes in brown adipocytes, whereas disruption of a GATA2 allele in brown
      preadipocytes resulted in significantly elevated differentiation and expression
      of several markers of brown adipogenesis. Collectively, these results show that
      GATA2 functions to suppress brown adipocyte differentiation, whereas reduction of
      GATA2 promotes brown adipogenesis.

PMID- 16082386
TI  - Glyceraldehyde 3-phosphate dehydrogenase serves as an accessory protein of the
      cardiac sarcolemmal K(ATP) channel.
AB  - Cardiac sarcolemmal ATP-sensitive K+ (K(ATP)) channels, composed of Kir6.2 and
      SUR2A subunits, are regulated by intracellular ATP and they couple the metabolic
      status of the cell with the membrane excitability. On the basis of previous
      studies, we have suggested that glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
      may be a part of the sarcolemmal K(ATP)-channel protein complex. A polypeptide of
      approximately 42 kDa was immunoprecipitated with an anti-SUR2A antibody from
      guinea-pig cardiac membrane fraction and identified as GAPDH.
      Immunoprecipitation/western blotting analysis with anti-Kir6.2, anti-SUR2A and
      anti-GAPDH antibodies showed that GAPDH is a part of the sarcolemmal K(ATP)
      channel protein complex in vivo. Further studies with immunoprecipitation/western
      blotting and the membrane yeast two-hybrid system showed that GAPDH associates
      physically with the Kir6.2 but not the SUR2A subunit. Patch-clamp
      electrophysiology showed that GAPDH regulates K(ATP)-channel activity
      irrespective of high intracellular ATP, by producing 1,3-bisphosphoglycerate, a
      K(ATP)-channel opener. These results suggest that GAPDH is an integral part of
      the sarcolemmal K(ATP)-channel protein complex, where it couples glycolysis with
      the K(ATP)-channel activity.

PMID- 16082387
TI  - Inhibition of apoptosis by Nur77 through NF-kappaB activity modulation.
AB  - The orphan nuclear receptor Nur77 has been described as a mediator of apoptosis
      and has also been associated with growth promotion and apoptotic resistance. This
      study aimed at evaluating the contribution of Nur77 to different apoptotic
      stimuli. Nur77 overexpression in the fibroblastic cell line HEK293 promoted
      resistance to programmed cell death induced by death receptor engagement, DNA
      damaging agents and endoplasmic reticulum stress. Nur77 overexpression led to
      enhanced NF-kappaB activity, and DNA-binding inhibitors confirmed the
      contribution of NF-kappaB to Nur77 antiapoptotic activity. Nur77 overexpression
      leads to NF-kappaB-dependent induction of the antiapoptotic gene cIAP1.
      Paradoxically, while dominant-negative Nur77 expression sensitised cells to Fas
      ligand-induced cell death, it protected cells from endoplasmic reticulum stress
      apoptosis in a manner similar to wild-type Nur77. These results show that nuclear
      crosstalk between Nur77 and other transcription factors contribute to cell fate
      in response to different apoptosis-inducing agents.

PMID- 16082388
TI  - Silencing of SH-PTP2 defines a crucial role in the inactivation of epidermal
      growth factor receptor by 5-aminosalicylic acid in colon cancer cells.
AB  - Recent studies have suggested that 5-aminosalicylic acid (5-ASA) inhibits
      colorectal cancer (CRC) development. However, the mechanism underlying the
      antineoplastic effect of 5-ASA remains unknown. We here examined the effect of 5
      ASA on epidermal growth factor receptor (EGFR) activation, a pathway that
      triggers mitogenic signals in CRC cells. We show that 5-ASA inhibits EGFR
      activation, through a mechanism that does not rely on CRC cell death induction. 5
      ASA enhances the activity, but not expression, of phosphorylated (p)-EGFR
      targeting phosphatases (PTPs), and treatment of cells with PTP inhibitors
      abrogates the 5-ASA-mediated EGFR dephosphorylation. Both SH-PTP1 and SH-PTP2
      interact with EGFR upon 5-ASA treatment. However, knockdown of SH-PTP2 but not SH
      PTP1 by small interference RNAs prevents the 5-ASA-induced EGFR
      dephosphorylation. Finally, we show that 5-ASA attenuates p-EGFR in ex vivo organ
      cultures of CRC explants. Data indicate that 5-ASA disrupts EGFR signalling by
      enhancing SH-PTP2 activity, and suggest a mechanism by which 5-ASA interferes
      with CRC growth.

PMID- 16082389
TI  - Agonists of an ecdysone-inducible mammalian expression system inhibit Fas Ligand-
      and TRAIL-induced apoptosis in the human colon carcinoma cell line RKO.
AB  - The ecdysone-inducible mammalian expression system is frequently used for
      inducible transgene expression in vitro and in vivo. Here, we describe a strong
      antiapoptotic effect of ecdysone analogs in the human colon carcinoma cell line
      RKO, which is in contrast to published data that ecdysteroids do not influence
      mammalian cell physiology. Inhibition of Fas ligand- and TNF-related apoptosis
      inducing ligand-induced apoptosis by muristerone A occurs at the level of caspase
      8 activation and is neutralized by phosphatidylinositol-3-kinase/Akt, protein
      kinase C and mitogen-activated protein kinase inhibitors. Microarray, Northern
      and Western blot analysis revealed that incubation of RKO cells with muristerone
      A leads to changes in gene expression levels, including an upregulation of bcl
      x(L) mRNA and protein levels. Our data imply that ecdysteroids and ecdysone
      mimics can induce and/or repress gene transcription in RKO and other mammalian
      cells, thereby influencing the apoptotic behavior. Therefore, the ecdysone
      inducible mammalian expression system may not be suitable for the analysis of
      apoptosis-related genes.

PMID- 16082390
TI  - Spontaneous regression of choroidal melanoma.

PMID- 16082391
TI  - A case of bilateral Adie's pupil following acute pancreatitis.

PMID- 16082392
TI  - Pre-eclampsia resulting in central retinal vein occlusion.

PMID- 16082393
TI  - Phenol red thread test vs Schirmer's test: a comparative study.
AB  - AIM: To measure the agreement between Schirmer's and phenol red thread tests in
      detecting dry eyes. PATIENTS AND METHODS: A total of 103 patients attending
      preoperative cataract assessment clinic who agreed to be involved in the study
      were recruited. Each patient had one eye examined by both tests in a random order
      by two different investigators who were unaware of the results of the other test.
      Dry eye symptoms were assessed using an interviewer-administered questionnaire.
      The data were collected after the study period and analysed using kappa
      statistics to assess the agreement between the two tests. RESULTS: Schirmer's
      test was positive in 25 patients when a cutoff point of 5 mm was used and
      positive in 41 patients with a cutoff point of 10 mm. Phenol red thread test was
      positive in four patients when a cutoff point of 10 mm was used and in 32
      patients with a cutoff point of 20 mm. Kappa ranged from 0.067 to 0.3 indicating
      very weak agreement between the two tests. In all, 27% of the patients had
      symptoms of dry eyes; however, the agreement between each test and the symptoms
      was very poor. CONCLUSION: There is very weak agreement between Schirmer's test
      and phenol red thread tests and between each test and symptoms of dry eyes.

PMID- 16082394
TI  - General practitioner with special interest improves the efficiency of glaucoma
      referrals.

PMID- 16082395
TI  - Visualization of primary uveal melanoma with PET/CT scan.

PMID- 16082396
TI  - Inappropriate investigation and management of a retinal vascular occlusion.

PMID- 16082397
TI  - Medically unexplained visual loss.

PMID- 16082398
TI  - Low power vs standard power transpupillary thermotherapy in patients with age
      related macular degeneration and subfoveal choroidal neovascularization
      ineligible for photodynamic therapy.
AB  - AIM: To assess the effect of standard power vs low power transpupillary
      thermotherapy (TTT) in patients with active subfoveal choroidal
      neovascularization secondary to age-related macular degeneration ineligible for
      photodynamic therapy (PDT) by original treatment of age-related macular
      degeneration with photodynamic therapy (TAP) study group recommendations.
      METHODS: Retrospective review of 79 patients with active predominantly occult
      subfoveal choroidal neovascularization or predominantly classic subfoveal
      choroidal neovascularization but Snellen visual acuity <20/200. All patients were
      treated with TTT administered via a Mainster wide field fundus contact lens with
      a retinal power/diameter coefficient of 248 mW/mm in the standard power (n=27)
      and 181 mW/mm in the low power group (n=52). The primary outcome was
      stabilization (<1 Snellen line change) or improvement (two or more Snellen lines)
      in visual acuity. Clinical and fluorescein angiographic resolution of overlying
      exudation was documented. RESULTS: At 24 month follow-up, 17 patients (63%) in
      the standard power and 36 patients (69%) in the low power group achieved stable
      or improved vision. Improved vision (mean three lines) was observed in 22% of the
      standard power and 23% of the low power group. Overlying exudation was reduced
      clinically with minimal or no leakage on fluorescein angiogram in 85% of standard
      power and 90% of low power group. Subgroup analysis in the low power group
      demonstrated a visual benefit in patients with subfoveal lesions, which had any
      classic component. CONCLUSIONS: Low power TTT is as effective as standard power
      in stabilizing or improving vision and reducing overlying exudation in patients
      with active subfoveal choroidal neovascularization ineligible for PDT.

PMID- 16082399
TI  - Exclusion of LCA5 locus in a consanguineous Turkish family with macular coloboma
      type LCA.
AB  - BACKGROUND: Leber's congenital amaurosis (LCA) is an inherited retinal dystrophy,
      which causes severe visual impairment in early childhood. Recent molecular
      genetic studies have linked 11 loci (AIPL1, CRB1, CRX, GUCY2D, RPE65, RDH12,
      RPGRIP1, TULP1, LCA3, LCA5, and LCA9) to LCA. LCA5 is a new locus, which maps to
      the 6q11-q16 chromosomal region and was found to be associated with macular
      coloboma-type LCA in a Pakistani family. Herein, we describe the molecular
      genetic features of a consanguineous Turkish family in which four children have
      macular coloboma-type LCA. METHODS: Haplotype analysis was performed on the DNA
      of the family members using microsatellite markers against GUCY2D, RPE65, and
      LCA5. Genomic DNA was screened for mutations by means of single-strand
      conformational polymorphism (SSCP) analysis in exons of the RPE65 and CRX genes.
      RESULTS: In haplotype analysis, no linkage to LCA5 or GUCY2D loci was detected.
      None of the tested markers showed homozygosity or segregation between affected
      siblings. PCR-SSCP mutation analysis revealed no mutations in the screened RPE65
      and CRX genes. CONCLUSION: We excluded LCA5 as the genetic cause of macular
      coloboma-type LCA in this Turkish family. Macular coloboma-type LCA shows genetic
      heterogeneity and it is not possible to establish a phenotype-genotype
      correlation with LCA5 and macular coloboma.

PMID- 16082400
TI  - Optical coherence tomography of macular crystalline opacities associated with
      chronic retinal detachment.

PMID- 16082401
TI  - Review of first year result of photodynamic therapy on age-related macular
      degeneration in Chinese population.
AB  - PURPOSE: To evaluate the effect of verteporfin therapy (Visudyne) on age-related
      macular degeneration (AMD) in Chinese patients. The baseline characteristic and
      the visual outcome will be compared with the treatment of AMD with photodynamic
      therapy study (TAP) and verteporfin in photodynamic therapy study (VIP). DESIGN:
      Retrospective comparative case series. METHOD: We recruited patients >50 years
      old, with best-corrected visual acuity >20/200 and fluorescein angiography
      documenting subfoveal either predominantly classic with greatest linear dimension
      <5400 mum or pure occult choroidal neovascularization (CNV) secondary to AMD. We
      applied non-thermal laser to the lesion 15 min after visudyne infusion as
      described in TAP study. Patients were followed up with fluorescein angiography
      every 3 months. Additional treatment would be offered if there was evidence of
      recurrence of CNV. OUTCOME MEASURE: Baseline characteristic and visual outcome.
      RESULT: In all, 46 eyes of 42 patients were enrolled at our centre from July 2002
      to June 2003. They comprised 11 eyes with predominantly classic lesions and 35
      eyes with pure occult lesion. The mean number of treatment sessions given was 2.9
      in the first year. At the 12-month examination, there were 63 and 29% of patients
      showing visual improvement in predominantly classic and occult groups,
      respectively, while there were only 16% of patients in the TAP study and 12% of
      patients in the VIP study showing visual improvement in the same period.
      CONCLUSION: Verteporfin therapy for subfoveal CNV is beneficial to Chinese
      patients with AMD at first year. The visual result seems to be better than that
      observed in Caucasian patients.

PMID- 16082402
TI  - Smoking and pregnancy.

PMID- 16082403
TI  - Community based maternal and child health care in Nepal: self-reported
      performance of Maternal and Child Health Workers.
AB  - The performance of a sample of 112 refresher trained Maternal and Child Health
      Workers (MCHW) was assessed over a nine-month period, using a self-reporting
      questionnaire. The findings show that the MCHWs are providing obstetric services,
      including antenatal care, birth attendance and postnatal and newborn care, at
      community level and identifying complications for referral, but their
      productivity levels are very low, particularly in the remote hill areas, where
      they are most needed. In order to increase their effectiveness, greater emphasis
      needs to be placed on the creation of an enabling environment, both in terms of
      professional support and recognition at community level. This requires more
      technical and logistical backup and the promotion of greater awareness amongst
      women and their families about the importance of midwifery care and skilled birth
      attendance.

PMID- 16082404
TI  - Aortic aneurysm and dissection: evaluation with spiral CT angiography.
AB  - The study was undertaken for aortic evaluation and to see its usefulness for
      assessing aortic aneurysm, aortic dissection and pseudoaneurysm by spiral CT
      angiography (CTA). A total of 28 patients with aortic aneurysm (n=19), aortic
      dissection (n=5) and aortic pseudoaneurysm (n=4) were included. CTA findings were
      compared with ultrasonography in 14, digital subtraction angiography (DSA) in 14,
      MRI in 9; and surgical findings in 12 patients. CTA was an excellent imaging
      modality for comprehensive evaluation of aortic aneurysm, dissection and
      pseudoaneurysm combining the advantage of conventional contrast enhanced CT axial
      images and those of angiography in the form of 3D reformatted images.

PMID- 16082405
TI  - Tuberculin survey in government high school of Dharan municipality.
AB  - This survey was done in 682 out of 1672 children tested with Batch of Tuberculin
      used for Testing (PPD RT 23 with Tween 80) in Jan. 1997 with financial research
      grant of B.P. Koirala Institute of Health Sciences, Dharan. Dharan City is
      situated in Eastern Development Region (EDR) of Nepal where a high percentage of
      migrated population is residing with very high number of sputum positive cases.
      The majority of population are from high hills and mountain region where the
      Annual Risk of Infection (ARI) is less. This survey was done to know the
      epidemiological situation of Tuberculosis (TB) in Dharan. Tuberculin survey was
      done in Eastern Development Region (EDR) (1994) by National Tuberculosis Centre
      (NTC)/Japan International Cooperation Agency (JICA) in Saptari and Morang. The
      reported result of average Annual Risk of Infection (ARI) is 2.49% and 2.38%
      respectively. The mean age of surveyed population was 14.8 yrs. The Bacilli
      Calmette Guerin (BCG) coverage (scar rate) was 38.3% and BCG 4-8 age group 83.3%
      was highest and it gradually decreased to 37.5% in 12 + age group. The average 23
      Tween-8-Batch of Tuberculin used for Testing (PPD) positive is 33.6% with 10 mm
      induration as cutoff line. Annual Risk of Infection (ARI) based on above was 2.7%
      in 9-11 age group and 1.31% in 12 + age group. This survey is suggestive of
      tuberculosis being highly prevalent in Dharan. The survey also showed average ARI
      to be 2.44% in Dharan in 10-15 yrs age group. The finding is suggestive of high
      ARI although the populations has migrated from hill and mountain. Previous report
      of average ARI in this area was 2.5% (Morang and Saptari). The survey result
      suggests that high priority, effective tuberculosis program is necessary and
      intensive control program can only give impact to control of tuberculosis in
      Dharan.

PMID- 16082406
TI  - Epidemiology of typhoid and paratyphoid fever in Kathmandu: two years study and
      trends of antimicrobial resistance.
AB  - Enteric fever is prevalent in developing countries including Nepal, where it
      still remains as a major health problem. Appropriate antibiotics are essential
      for the treatment of typhoid and paratyphoid fever. A prospective study was
      carried out to characterize the epidemiological features of enteric fever in
      Kathmandu, Nepal and to analyse the recent trend of antimicrobial resistance
      pattern of the Salmonella isolated from the cases of enteric fever from different
      hospitals in Kathmandu during June, 2002 to June, 2004. A total of 1469
      Salmonella typhi and Salmonella paratyphi 'A' isolates collected during this
      period from five different hospital laboratories situated in Kathmandu were
      studied. The antimicrobial susceptibilities of the isolates towards Ampicillin
      (10 mcg), Chloramphenicol (30 mcg), Cotrimoxazole (25 mcg), Ciprofloxacin (5 mcg)
      and Ceftriaxone (5 mcg) were determined by standard disc diffusion technique and
      Agar dilution technique were used to determine the minimum inhibitory
      concentration (MIC) for Ampicillin, Ciprofloxacin, Chloramphenicol and
      Ceftriaxone. All the isolates tested were found to be sensitive to Ceftriaxone
      and Ciprofloxacin, the most commonly used antibiotic for treatment of enteric
      fever in Nepal. Of the total isolates studied, 15.5% from 2002, 8% from 2003 and
      3.45% from 2004 were found to be multidrug resistant (exhibiting resistance
      towards Ampicillin, Chloramphenicol and Cotrimoxazole). Of the total multi drug
      resistant Salmonella isolates, 92% were Salmonella typhi. All the multidrug
      resistant isolates were also further tested for susceptibilities towards
      Tetracycline (30 mcg), Nalidixic acid (30 mcg), Streptomycin (10 units),
      Gentamycin (25 mcg), Azithromycin (15 mcg), Kanamycin (30 mcg), Neomycin (30
      mcg). 50% of the multi drug resistant Salmonella typhi were also resistant to
      Tetracycline. Plasmid analysis revealed that all of the multidrug resistant
      Salmonella typhi isolates with Tetracycline resistance harbored a large molecular
      weight (147 Kb) plasmid.

PMID- 16082407
TI  - Paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hemolytic disorder of
      acquired origin and is clinically manifested by chronic hemolysis, thromboses in
      various sites, and bone marrow failure. The disease is so rare that the delay in
      the diagnosis is not uncommon and this bears a tremendous impact on patient
      management. We present this case to draw attention to this uncommon cause of
      hemolytic anemia, which should be considered in any patient, of any age, who has
      signs of chronic hemolysis.

PMID- 16082409
TI  - Advantage of a baculovirus expression system for protein-protein interaction
      studies. Involvement of posttranslational phosphorylation in the interaction
      between wt p53 protein and poly(ADP-ribose) polymerase-1.
AB  - We recently observed an interaction between poly(ADP-ribose) polymerase-1 (PARP
      1) and the tumor suppressor p53 protein. However, more extensive studies on both
      proteins, especially those on characterization of their domains involved in the
      interaction were difficult due to very low expression levels of p53 in mammalian
      cells. Therefore, we generated recombinant proteins for such studies. To clarify
      which domains of human PARP-1 and of human wild-type (wt) p53 were involved in
      this protein-protein interaction, we generated baculoviral constructs encoding
      full length or distinct functional domains of both proteins. Full length PARP-1
      was simultaneously coexpressed in insect cells with full length wt p53 protein or
      its distinct truncated fragments and vice versa. Reciprocal immunoprecipitation
      of Sf9 cell lysates revealed that the central and carboxy-terminal fragments of
      p53 each were sufficient to confer binding to PARP-1, whereas the amino-terminal
      part harbouring the transactivation functional domain was dispensable. On the
      other hand, the amino-terminal and central fragments of PARP-1 were both
      necessary for complex formation with p53 protein. Since the most important
      features of p53 protein are regulated by phosphorylation, we addressed the
      question whether its phosphorylation is essential for the binding between the two
      proteins. Baculovirally expressed wt p53 was post-translationally modified. At
      least six distinct p53 isomers were resolved by immunoblotting following two
      dimensional separation of baculovirally expressed wt p53 protein. Using specific
      phospho-serine antibodies, we identified phosphorylation of baculovirally
      expressed p53 protein at five distinct sites. To define the role of p53
      phosphorylation, pull-down assays using untreated and dephosphorylated p53
      protein were performed. Dephosphorylated p53 failed to bind PARP-1, indicating
      that complex formation between the two proteins was regulated by phosphorylation
      of p53. The marked phosphorylation of p53 at Ser392 observed in unstressed cells
      suggests that the phosphorylated carboxy-terminal part of p53 undergoes complex
      formation with PARP-1 resulting in masking of the NES and thereby preventing its
      export.

PMID- 16082408
TI  - Helper-dependent adenoviral vectors in experimental gene therapy.
AB  - In the majority of potential applications gene therapy will require an effective
      transfer of a transgene in vivo resulting in high-level and long-term transgene
      expression, all in the absence of significant toxicity or inflammatory responses.
      The most efficient vehicles for delivery of foreign genes to the target tissues
      are modified adenoviruses. Adenoviral vectors of the first generation, despite
      the high infection efficacy, have an essential drawback: they induce strong
      immune response, which leads to short term expression of the transgene, and
      limits their usefulness in clinical trials. In contrast, helper-dependent
      adenoviral vectors (HdAd) lacking all viral coding sequences display only minimal
      immunogenicity and negligible side-effects, allowing for long-term transgene
      expression. Thus, HdAd vehicles have become the carrier of choice for adenoviral
      vector-mediated experimental gene therapy, effectively used in animal models for
      delivery of transgenes into the liver, skeletal muscle, myocardium or brain.
      Strong and long-lasting expression of therapeutic genes has allowed for
      successful treatment of dyslipidemias, muscular dystrophy, obesity, hemophilia,
      and diabetes. Additionally, the large cloning capacity of HdAd, up to 37 kb,
      facilitates the use of physiologically regulated, endogenous promoters, instead
      of artificial viral promoter sequences. This enables also generation of the
      single vectors expressing multiple genes, which can be potentially useful for
      treatment of polygenic diseases. In this review we characterize the basic
      features of HdAd vectors and describe some of their experimental and potential
      clinical applications.

PMID- 16082410
TI  - Glucosamine-6-phosphate synthase, a novel target for antifungal agents. Molecular
      modelling studies in drug design.
AB  - Fungal infections are a growing problem in contemporary medicine, yet only a few
      antifungal agents are used in clinical practice. In our laboratory we proposed
      the enzyme L-glutamine: D-fructose-6-phosphate amidotransferase (EC 2.6.1.16) as
      a new target for antifungals. The structure of this enzyme consists of two
      domains, N-terminal and C-terminal ones, catalysing glutamine hydrolysis and
      sugar-phosphate isomerisation, respectively. In our laboratory a series of potent
      selective inhibitors of GlcN-6-P synthase have been designed and synthesised. One
      group of these compounds, including the most studied N3-(4-methoxyfumaroyl)-l-2,3
      diaminopropanoic acid (FMDP), behave like glutamine analogs acting as active-site
      directed inactivators, blocking the N-terminal, glutamine-binding domain of the
      enzyme. The second group of GlcN-6-P synthase inhibitors mimic the transition
      state of the reaction taking place in the C-terminal sugar isomerising domain.
      Surprisingly, in spite of the fact that glutamine is the source of nitrogen for a
      number of enzymes it turned out that the glutamine analogue FMDP and its
      derivatives are selective against GlcN-6-P synthase and they do not block other
      enzymes, even belonging to the same family of glutamine amidotransferases. Our
      molecular modelling studies of this phenomenon revealed that even within the
      family of related enzymes substantial differences may exist in the geometry of
      the active site. In the case of the glutamine amidotransferase family the
      glutamine binding site of GlcN-6-P synthase fits a different region of the
      glutamine conformational space than other amidotransferases. Detailed analysis of
      the interaction pattern for the best known, so far, inhibitor of the sugar
      isomerising domain, namely 2-amino-2-deoxy-D-glucitol-6-phosphate (ADGP), allowed
      us to suggest changes in the structure of the inhibitor that should improve the
      interaction pattern. The novel ligand was designed and synthesised. Biological
      experiments confirmed our predictions. The new compound named ADMP is a much
      better inhibitor of glucosamine-6-phosphate synthase than ADGP.

PMID- 16082411
TI  - MutS as a tool for mutation detection.
AB  - MutS, a DNA mismatch-binding protein, seems to be a promising tool for mutation
      detection. We present three MutS based approaches to the detection of point
      mutations: DNA retardation, protection of mismatched DNA against exonuclease
      digestion, and chimeric MutS proteins. DNA retardation in polyacrylamide gels
      stained with SYBR-Gold allows mutation detection using 1-3 microg of Thermus
      thermophilus his6-MutS protein and 50-200 ng of a PCR product. The method enables
      the search for a broad range of mutations: from single up to several nucleotide,
      as mutations over three nucleotides could be detected in electrophoresis without
      MutS, due to the mobility shift caused by large insertion/deletion loops in
      heteroduplex DNA. The binding of DNA mismatches by MutS protects the complexed
      DNA against exonuclease digestion. The direct addition of the fluorescent dye,
      SYBR-Gold, allows mutation detection in a single-tube assay. The limited
      efficiency of T4 DNA polymerase as an exonuclease hampers the application of the
      method in practice. The assay required 300-400 ng of PCR products in the range of
      200-700 bp and 1-3 microg of MutS. MutS binding to mismatched DNA immobilised on
      a solid phase can be observed thanks to the activity of a reporter domain linked
      to MutS. We obtained chimeric bifunctional proteins consisting of T. thermophilus
      MutS and reporter domains, like beta-galactosidase or GFP. Very low detection
      limits for beta-galactosidase could theoretically enable mutation detection not
      only by the examination of PCR products, but even of genomic DNA.

PMID- 16082412
TI  - Single-stranded DNA-binding proteins (SSBs) -- sources and applications in
      molecular biology.
AB  - Single-stranded DNA-binding proteins (SSBs) play essential roles in DNA
      replication, recombination, and repair in bacteria, archaea and eukarya. The SSBs
      share a common core ssDNA-binding domain with a conserved OB
      (oligonucleotide/oligosaccharide binding) fold. This ssDNA-binding domain was
      presumably present in the common ancestor to all three major branches of life. In
      recent years, there has been an increasing interest in SSBs because they are
      useful for molecular biology methods and for analytical purposes. In this review,
      we concentrate on recent advances in the discovery of new sources of SSBs as well
      as certain aspects of their applications in analytical sciences.

PMID- 16082413
TI  - Targeting drug-efflux pumps -- a pharmacoinformatic approach.
AB  - In line with our studies on propafenone-type inhibitors of P-glycoprotein (P-gp),
      we applied several methods to approach virtual screening tools for identification
      of new P-gp inhibitors on one hand and the molecular basis of ligand-protein
      interaction on the other hand. For virtual screening, a combination of
      autocorrelation vectors and selforganising artificial neural networks proved
      extremely valuable in identifying P-gp inhibitors with structurally new
      scaffolds. For a closer view on the binding region for propafenone-type ligands
      we applied a combination of pharmacophore-driven photoaffinity labeling and
      protein homology modeling. On LmrA, a bacterial homologue of P-gp, we were able
      to identify distinct regions on transmembrane helices 3, 5 and 6 which show
      significant changes in the labeling pattern during different steps of the
      catalytic cycle.

PMID- 16082414
TI  - Molecular simulation of adsorption from dilute solutions.
AB  - Adsorption of biomolecules on surfaces is a perennial and general challenge
      relevant to many fields in biotechnology. A change of the Helmholtz free energy
      DeltaA takes place when a molecule becomes adsorbed out of a bulk solution. The
      purpose of our investigations is to explore routes for the calculation of DeltaA
      by molecular simulations. DeltaA can be obtained both by integration over the
      mean force on a molecule and via the local density. It turns out that the route
      via the potential of mean force prevails over the latter due to better
      consistency. In this work we present results for systems of 1-centre and 2-centre
      Lennard-Jones mixtures at a 9/3 Lennard-Jones wall.

PMID- 16082415
TI  - Time-dependent effect of leptin on renal Na+,K+-ATPase activity.
AB  - Leptin, secreted by adipose tissue, is involved in the pathogenesis of arterial
      hypertension, however, the mechanisms through which leptin increases blood
      pressure are incompletely elucidated. We investigated the effect of leptin,
      administered for different time periods, on renal Na(+),K(+)-ATPase activity in
      the rat. Leptin was infused under anesthesia into the abdominal aorta proximally
      to the renal arteries for 0.5-3 h. Leptin administered at doses of 1 and 10
      microg/min per kg for 30 min decreased the Na(+),K(+)-ATPase activity in the
      renal medulla. This effect disappeared when the hormone was infused for > or =1
      h. Leptin infused for 3 h increased the Na(+),K(+)-ATPase activity in the renal
      cortex and medulla. The stimulatory effect was abolished by a specific inhibitor
      of Janus kinases (JAKs), tyrphostin AG490, as well as by an NAD(P)H oxidase
      inhibitor, apocynin. Leptin increased urinary excretion of hydrogen peroxide
      (H(2)O(2)) between 2 and 3 h of infusion. The effect of leptin on renal
      Na(+),K(+)-ATPase and urinary H(2)O(2) was augmented by a superoxide dismutase
      mimetic, tempol, and was abolished by catalase. In addition, infusion of H(2)O(2)
      for 30 min increased the Na(+),K(+)-ATPase activity. Inhibitors of extracellular
      signal regulated kinases (ERKs), PD98059 or U0126, prevented Na(+),K(+)-ATPase
      stimulation by leptin and H(2)O(2). These data indicate that leptin, by acting
      directly within the kidney, has a delayed stimulatory effect on Na(+),K(+)
      ATPase, mediated by JAKs, H(2)O(2) and ERKs. This mechanism may contribute to the
      abnormal renal Na(+) handling in diseases associated with chronic hyperleptinemia
      such as diabetes and obesity.

PMID- 16082416
TI  - Research on adverse drug events. I. Muscarinic M3 receptor binding affinity could
      predict the risk of antipsychotics to induce type 2 diabetes.
AB  - Antipsychotics are associated with a wide range of adverse effects, several of
      which may represent a serious health risk to patients. There is an increased
      concern about metabolic disturbances associated with antipsychotics, including
      weight gain, dyslipidemia, hyperglycemia, and type 2 diabetes. However, little is
      known about the mechanisms underlying antipsychotic-induced metabolic
      disturbances and, in particular, those related to the induction of abnormal
      glucose metabolism and diabetes. The present article aimed to identify those
      receptor(s) that are most likely to be involved with or mediate antipsychotics
      induced diabetes. Two independent measures taken from literature to indicate the
      risk of type 2 diabetes associated with 25 typical and atypical antipsychotic
      drugs were considered, along with their binding affinities to 21 specific
      receptors (obtained from the resources of Prous Science Integrity). A range of
      both exploratory and predictive statistical analyses were applied, including
      principal component factorial analysis, multivariable linear regression analysis,
      and discriminant analysis. Binding affinities (pKi) to human neurotransmitter
      receptors and monoaminergic transporters were used as independent variables
      (predictors). Measures to determine the risk to induce new-onset type 2 diabetes
      associated with each antipsychotic, logistic regression odds-ratio (dOR) and a
      discrete scale-based risk (three levels: 'low,' 'moderate,' 'high'), were used as
      the dependent variables (criteria). Similarly, parallel analyses were also
      conducted for other measures (average effective therapeutic dose) or adverse
      effects (weight gain, extrapyramidal side effects, hyperprolactinemia,
      anticholinergic, hypotension, and sedation) associated with antipsychotics, where
      underlying mechanisms have been previously established and, therefore, serve as
      positive-control references. Affinity for the cholinergic muscarinic M3 receptor
      subtype was presented as the best predictor for the propensity of antipsychotics
      to induce type 2 diabetes. This was independently revealed by means of multiple
      linear regression analysis, using the dOR as criterion (R=0.90, p<0.0001), and
      discriminant analysis, using the scale-based risk of type 2 diabetes (3 levels)
      as criterion (Wilks' lambda=0.33, chi2=14.11, p<0.001). To our knowledge, this
      study provides the first direct evidence to indicate that antipsychotic agents
      with high binding affinity to the muscarinic M3 receptor are associated with an
      elevated risk for type 2 diabetes. Rationale of the M3 receptor involvement in
      this adverse effect is discussed further in relation to M3 receptor mediation of
      glucose-dependent parasympathetic acetylcholine regulation of insulin secretion
      by pancreatic beta-cells. This study is the first in a series of investigations
      that aim to further our understanding of mechanisms underlying adverse drug
      effects.

PMID- 16082417
TI  - In vivo assessment of the cutaneous bioavailability of topically applied
      maxacalcitol.
AB  - Maxacalcitol (22-oxacalcitriol), a vitamin D3 analogue, is widely used for the
      treatment of psoriasis. The effects of topical dermatologic drugs have been
      assessed by their pharmacodynamic activities, and concentrations in the skin
      correlate with these activities. In this study, we assessed the cutaneous
      bioavailability of topically applied maxacalcitol ointment in vivo by tape
      stripping. Six drug application sites were randomly assigned on the left volar
      forearm of six healthy men. Fifty milligrams of maxacalcitol ointment (25
      microg/g) was applied to each site. After 0 (15 s), 0.5, 1, 2, 4, or 6 h, the
      ointment was gently removed, and tape stripping was performed. Maxacalcitol was
      extracted from the tape strips and quantified by liquid chromatographic tandem
      mass spectrometry. Average concentrations of maxacalcitol in the stratum corneum
      (SC) were 2.61, 4.37, 6.23, 9.37, and 9.46 microg/g at 0.5, 1, 2, 4, and 6 h,
      respectively, after drug application. The steady state was attained approx. 4 h
      after drug application. The cutaneous bioavailability of topical maxacalcitol
      ointment can be assessed by the tape-stripping method. This approach will
      probably be useful in the assessment of the bioequivalence of topical
      dermatologic products and as a parameter for pharmacokinetic/pharmacodynamic
      studies.

PMID- 16082418
TI  - Estrogen, but not testosterone, down-regulates cytokine production in nicotine
      induced murine macrophage.
AB  - We have investigated the effects of 17beta-estradiol (E2) and testosterone (Te)
      on the production of proinflammatory factors by nicotine-induced murine
      macrophage (Ana-1). Ana-1 pretreated with or without E2/Te was challenged with
      different doses of nicotine at various time points. TNF-alpha, IL-1beta IFN
      gamma, and IL-8 in the supernatant of Ana-1 were detected using radioimmunoassay
      (RIA) or enzyme-linked immunosorbent assay (ELISA). The presence of estrogen and
      androgen receptors in Ana-1 was detected by reverse transcription polymerase
      chain reaction (RT-PCR) and Western blotting. E2 could obviously suppress the
      expression of TNF-alpha and IL-1beta whereas Te could not. There were no obvious
      changes in the levels of either IL-8 or IFN-gamma in Ana-1 stimulated with
      nicotine or sex hormones (p>0.05). The antagonist tamoxifen of E2 abolished the
      effects of E2 on TNF-alpha and IL-1beta whereas the antagonist cyproterone of Te
      did not alter the effects of Te on Ana-1. Furthermore, RT-PCR and Western
      blotting showed that both the estrogen receptors (ER-alpha and ER-beta existed in
      Ana-1; however, androgen receptor (AR) was not detectable. Our data suggested
      that E2 could regulate the immunoreaction in the nicotine-induced inflammatory
      process possibly through classic intercellular ER, whereas Te had no significant
      effect in this process.

PMID- 16082419
TI  - Incidence and severity of infections according to the development of neutropenia
      during combined therapy with pegylated interferon-alpha2a plus ribavirin in
      chronic hepatitis C infection.
AB  - The evolution of treatment of chronic hepatitis C virus infection has led to
      improved therapeutic efficacy. However, a major problem is the presence of side
      effects that require modification or withdrawal of drug therapy in 15-20% of
      cases. This could potentially influence the lack of sustained viral response in
      50% of the cases. Side effects are common, even with pegylated interferon. This
      study aimed to assess the incidence and severity of infections based on the
      development of neutropenia associated with combined therapy with pegylated
      interferon-alpha2a plus ribavirin in 209 patients with chronic hepatitis C
      infection. All patients were administered pegylated interferon-alpha2a (180
      microg/week) plus ribavirin (800 mg/day for 24 weeks in cases of nongenotype 1,
      or 1000-1200 mg/day for 48 weeks for genotype 1, according to whether patients
      weighed more or less than 75 kg). Patients with preexisting neutropenia of any
      cause or cirrhosis were excluded. Neutropenia was defined as a neutrophil count
      (NC) of <1500 cells/microl. Neutropenia was classified into three levels during
      treatment: 750<or=NC<1500 (level 1), 500<or=750 (level 2), and NC<500
      cells/microl (level 3). Of the 209 patients, 114 did not develop neutropenia
      (mean 2100+/-804 cells/microl), while 95 had an NC<1500 cells/microl (mean 1100+/
      250 cells/microl). It was found that patients who developed neutropenia during
      treatment of chronic hepatitis C virus infection with a combined therapy based on
      pegylated interferon-alpha2a plus ribavirin did not show a higher infection rate
      or increased severity of the disease.

PMID- 16082420
TI  - Development of enzyme-linked immunosorbent assay for human cardiac myosin light
      chain I.
AB  - We have developed a new enzyme-linked immunosorbent assay (ELISA) for the
      determination of cardiac myosin light chain I (MLI) in human serum. The detection
      range of ELISA was between 1 and 50 ng/ml, and serial dilutions of human serum
      showed good linearity. The recovery of different concentrations of cardiac MLI
      ranged from 87.5% to 100.0%. The intra-assay (n=5) and inter-assay (n=5) showed
      good results (C.V.<10%). The cross-reactivity with skeletal-myosin light chain
      (ML) was rather high, but was negligible with other myosin light chains. The
      concentrations of cardiac MLI in human serum determined by ELISA were similar to
      those determined by immunoradiometric assay (IRMA). The total assay time and
      sample volume required for ELISA were approx. 2 h and 25 microl, respectively,
      while those for IRMA are approx. 24 h and 100 microl. Our novel ELISA method
      therefore has significant advantages for clinical analysis.

PMID- 16082421
TI  - In vivo tests of natural therapy, Tibetan yogurt or fresh broccoli, for
      Helicobacter pylori infection.
AB  - Plants and probiotics have a long history in the treatment of gastrointestinal
      ailments. Our aim was to evaluate the effectiveness of Tibetan yogurt and fresh
      broccoli tips in Helicobacter pylori- (H. pylori) infected volunteers, using the
      urea breath test (UBT) to assess the effect on H. pylori. Clinical trials
      consisted of ingestion of approximately 135 g of fresh, finely minced juvenile
      broccoli tips (var. Emperor) in commercial plain yogurt t.i.d, for ten servings
      (3.3 days) or ingestion of freshly made Tibetan yogurt whey (120 ml) given twice
      a day for 3.5 days. Urea breath testing was done before and after the natural
      therapies. Five volunteers received broccoli tips and seven received Tibetan
      yogurt. No trend for a beneficial effect was seen; the UBT results (delta over
      baseline) before and after yogurt (35.5+/-12.8 vs. 40.7+/-12.2) (p=0.76) or
      broccoli (15.8 vs. 19.4) (p=1.0) were unchanged. Antimicrobial end products
      derived from Tibetan yogurt or broccoli tips have little or no anti-H. pylori
      effect in vivo. It appears that the gastric mucosal microenvironment apparently
      shielded H. pylori. In vitro studies suggesting anti-H. pylori activity of
      compounds should be considered as hypotheses to be tested.

PMID- 16082422
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials is a guide to the most recent clinical trials in
      current literature and congresses. The data in the following tables have been
      retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the
      drug discovery and development portal, http://integrity.prous.com. This issue
      focuses on the following selection of drugs: Abiraterone acetate, acyline,
      adalimumab, adenosine triphosphate, AEE-788, AIDSVAX gp120 B/B, AK-602,
      alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium,
      alprazolam, amdoxovir, AMG-162, aminolevulinic acid hydrochloride, aminolevulinic
      acid methyl ester, aminophylline hydrate, anakinra, anecortave acetate, anti-CTLA
      4 MAb, APC-8015, aripiprazole, aspirin, atazanavir sulfate, atomoxetine
      hydrochloride, atorvastatin calcium, atrasentan, AVE-5883, AZD-2171;
      Betamethasone dipropionate, bevacizumab, bimatoprost, biphasic human insulin
      (prb), bortezomib, BR-A-657, BRL-55730, budesonide, busulfan; Calcipotriol,
      calcipotriol/betamethasone dipropionate, calcium folinate, capecitabine,
      capravirine, carmustine, caspofungin acetate, cefdinir, certolizumab pegol, CG
      53135, chlorambucil, ciclesonide, ciclosporin, cisplatin, clofarabine,
      clopidogrel hydrogensulfate, clozapine, co-trimoxazole, CP-122721, creatine, CY
      2301, cyclophosphamide, cypher, cytarabine, cytolin; D0401, darbepoetin alfa,
      darifenacin hydrobromide, DASB, desipramine hydrochloride, desloratadine,
      desvenlafaxine succinate, dexamethasone, didanosine, diquafosol tetrasodium,
      docetaxel, doxorubicin hydrochloride, drotrecogin alfa (activated), duloxetine
      hydrochloride, dutasteride; Ecallantide, efalizumab, efavirenz, eletriptan,
      emtricitabine, enfuvirtide, enoxaparin sodium, estramustine phosphate sodium,
      etanercept, ethinylestradiol, etonogestrel, etonogestrel/ethinylestradiol,
      etoposide, exenatide; Famciclovir, fampridine, febuxostat, filgrastim,
      fludarabine phosphate, fluocinolone acetonide, fluorouracil, fluticasone
      propionate, fluvastatin sodium, fondaparinux sodium; Gaboxadol, gamma
      hydroxybutyrate sodium, gefitinib, gelclair, gemcitabine, gemfibrozil,
      glibenclamide, glyminox; Haloperidol, heparin sodium, HPV 16/HPV 18 vaccine,
      human insulin, human insulin; Icatibant, imatinib mesylate, indium 111 (111In)
      ibritumomab tiuxetan, infliximab, INKP-100, iodine (I131) tositumomab, IoGen,
      ipratropium bromide, ixabepilone; L-870810, lamivudine, lapatinib, laquinimod,
      latanoprost, levonorgestrel, licochalcone a, liposomal doxorubicin, lopinavir,
      lopinavir/ritonavir, lorazepam, lovastatin; Maraviroc, maribavir, matuzumab, MDL
      100907, melphalan, methotrexate, methylprednisolone, mitomycin, mitoxantrone
      hydrochloride, MK-0431, MN-001, MRKAd5 HIV-1 gag/pol/nef, MRKAd5gag, MVA.HIVA,
      MVA-BN Nef, MVA-Muc1-IL-2, mycophenolate mofetil; Nelfinavir mesilate,
      nesiritide, NSC-330507; Olanzapine, olmesartan medoxomil, omalizumab, oral
      insulin, osanetant; PA-457, paclitaxel, paroxetine, paroxetine hydrochloride, PCK
      3145, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, perillyl
      alcohol, pexelizumab, pimecrolimus, pitavastatin calcium, porfiromycin,
      prasterone, prasugrel, pravastatin sodium, prednisone, pregabalin, prinomastat,
      PRO-2000, propofol, prostate cancer vaccine; Rasagiline mesilate, rhBMP-2/ACS,
      rhBMP-2/BCP, rhC1, ribavirin, rilpivirine, ritonavir, rituximab, Ro-26-9228,
      rosuvastatin calcium, rosuvastatin sodium, rubitecan; Selodenoson, simvastatin,
      sirolimus, sitaxsentan sodium, sorafenib, SS(dsFv)-PE38, St. John's Wort extract,
      stavudine; Tacrolimus, tadalafil, tafenoquine succinate, talaglumetad,
      tanomastat, taxus, tegaserod maleate, telithromycin, tempol, tenofovir, tenofovir
      disoproxil fumarate, testosterone enanthate, TH-9507, thalidomide, tigecycline,
      timolol maleate, tiotropium bromide, tipifarnib, torcetrapib, trabectedin,
      travoprost, travoprost/timolol, treprostinil sodium; Valdecoxib, vardenafil
      hydrochloride hydrate, varenicline, VEGF-2 gene therapy, venlafaxine
      hydrochloride, vildagliptin, vincristine sulfate, voriconazole, VRX-496, VX-385;
      Warfarin sodium; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan;
      Zanolimumab, zidovudine.

PMID- 16082423
TI  - Eberconazole cream: topical and general tolerability, sensitisation potential,
      and systemic availability.
AB  - Eberconazole is a topical imidazole derivative, which has shown high potency
      against dermatophytes and yeasts (several species of Candida, Malassezia) in
      vitro and in experimental models. Clinical trials have found that the compound
      has a high degree of efficacy against dermatophytes and good tolerability.
      Evaluation of its a) topical and general tolerability, b) eventual development of
      sensitisation, c) local availability, and d) degree of systemic absorption. Two
      clinical trials with 28 healthy young volunteers of both sexes were performed. In
      Study I, placebo or eberconazole cream (2%) were applied at increasing doses: day
      1 (0.5 g), days 2-3 (1 g), days 4-5 (2 g), days 6-7 (4 g), days 8-9 (8 g), and
      days 10-11 (12 g). On day 1, each application area was washed with ethanol-soaked
      gauzes at different times to assess availability of the active compound. In Study
      II, eberconazole cream (1%) was applied on day 1 and again at least one week
      later. After the first application, blood and urine samples were obtained at
      different times to assess systemic absorption. The only change observed was
      slight redness in a few volunteers after both active and placebo applications.
      This remitted spontaneously without intervention and we were able to continue
      with the administration of repeated increasing-doses. A few participants
      described side effects; these were all of mild intensity, and occurred in areas
      where placebo or eberconazole were applied, mainly within the first hour
      postapplication. The most frequent effect after the first application was
      coldness, and after repeated increasing-doses there was itching. No signs or
      symptoms of skin reactivity were observed following reexposure to the product. No
      clinically relevant changes were observed in vital signs (systolic and diastolic
      blood pressure, heart rate, body temperature), ECG, or analytical parameters
      (clinical haematology and biochemistry). The quantity of compound collected
      through washing gauzes decreased progressively over time. Plasma and urine
      concentrations of eberconazole were below the quantification limit of the
      analytical method (5 ng/ml) at all times. Eberconazole cream is a topical
      antimycotic drug that has good local and general tolerability. It has acceptable
      topical availability, no detectable systemic drug levels, and does not appear to
      cause skin sensitivity.

PMID- 16082424
TI  - Polymorphic variants of the beta2-adrenergic receptor (ADRB2) gene and ADRB2
      related propanolol-induced dyslipidemia in the Colombian population.
AB  - Different polymorphisms of the ADRB2 gene encoding the beta-adrenergic receptor
      (ADRB2) are associated with changes in a variety of responses of the sympathetic
      nervous system (SNS). In this study, we have investigated the distribution of
      frequencies of ADRB2-related allelic variants (Arg16Gly, Gln27Glu, Thr164Ile) in
      the Colombian population, as well as the influence of the Gln27Glu polymorphism
      as a risk factor for the development of dyslipidemia following propranolol
      administration. Genotyping was performed in unrelated Colombian volunteers, using
      PCR-RFLP methods. To examine the association between the Gln27Glu polymorphism of
      the ADRB2 gene and dyslipidemia induced by propranolol, we recruited 19 healthy
      individuals who were homozygous for either the Gln27 (wild-type, N = 11) or the
      Glu27 (homozygous mutant, N = 8) genotype. Electrocardiography (ECG), heart rate
      (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass
      index (BMI), serum lipid levels (T-CHO, HDL-CHO, TG), and fibrinogen were
      determined before and after propranolol administration. The distribution of
      genotypes was as follows: Arg16Arg 46%, Arg16Gly 47.4%, Gly16Gly 6.6%, Gln27Gln
      44.7%, Gln27Glu 48.2%, and Glu27Glu 7.1%, with allelic frequencies of 69.7% for
      Arg16, 30.3% for Gly16, 68.8% for Gln27, and 31.2% for Glu27. The Thr164Ile
      polymorphism was found only in one subject, who was heterozygous for the
      isoleucine variant. Significant changes in physiological parameters (HR, SBP,
      DBP) have been found in association with ADRB2 variants in both native and mutant
      subgroups after propranolol intake. HDL-CHO levels diminished (p = 0.005) in
      native homozygous individuals (Gln27Gln), whereas TG levels were found increased
      (p = 0.012) in the mutant homozygous individuals (Glu27Glu). T-CHO levels and
      serum fibrinogen levels remained unaltered in both subgroups. The evidence that
      subjects homozygous for Gln27 in the ADRB2 gene show a significant reduction of
      HDL-CHO levels, as well as the increased TG levels in subjects homozygous for
      Glu27 after propranolol administration, suggest that the Gln27Glu polymorphism
      represents a risk factor for dyslipidemia induced by propranolol. These results
      may contribute to a better understanding of the mechanisms underlying
      dyslipidemia induced by ADRB2 antagonists.

PMID- 16082425
TI  - Oral buspirone causes a shift in the dose-response curve between the elevated
      plus maze and Vogel conflict tests in Long-Evans rats: relation of brain levels
      of buspirone and 1-PP to anxiolytic action.
AB  - Most studies concerning the effects of oral buspirone in the rat elevated plus
      maze (EPM) test, spontaneous motor activity (SMA) test, and Vogel conflict (VC)
      test have used Sprague-Dawley or Wistar rats. Although it has been documented
      that the behavior of Long-Evans rats is more sensitive to detection of
      anxiolytics when compared to the aforementioned strains, the effects of oral
      buspirone have not been fully characterized in the Long-Evans strain in the EPM
      and VC tests. Thus, we studied the effects of orally administered buspirone (0.03
      10.0 mg/kg) in the EPM, SMA, and VC (0.3-60.0 mg/kg) tests in Long-Evans rats. In
      a separate experiment, brain and plasma concentrations of buspirone and 1-(2
      pyrimidinyl)-piperazine (1-PP) were determined after oral administration of
      buspirone (0.3 and 10 mg/kg) to relate the behavioral effects of buspirone with
      brain and plasma concentrations of buspirone and 1-PP. Our results showed that
      buspirone exhibited an inverted-U-shaped dose-response curve in both the EPM and
      the VC tests. In the EPM, buspirone produced anxiolytic activity in a low, narrow
      dose-range (0.03, 0.1, 0.3 mg/kg, p.o.) with maximum efficacy at 0.3 mg/kg,
      whereas in the VC test, significant anxiolytic activity was observed in a high,
      narrow dose-range (10, 30 mg/kg, p.o.) with maximum efficacy occurring at 10
      mg/kg. In the SMA test, buspirone (10 mg/kg, p.o.) significantly decreased
      horizontal activity and vertical movements suggestive of sedation. Also, one hour
      following oral doses of buspirone (0.3 and 10 mg/kg), both buspirone and 1-PP
      concentrations were higher in brain when compared with those in plasma.
      Additionally, the concentrations of 1-PP were always higher in brain and in
      plasma compared with the concentrations of buspirone. Of particular interest is
      our finding of the shift in the dose-response curve between the EPM and VC tests.
      This shift in the dose-response curve is discussed in relation to brain levels of
      buspirone and 1-PP levels and their anxiolytic action.

PMID- 16082426
TI  - Antinociceptive, antiinflammatory and antidiabetic effects of Leonotis leonurus
      (L.) R. BR. [Lamiaceae] leaf aqueous extract in mice and rats.
AB  - The present study was undertaken to investigate the antinociceptive,
      antiinflammatory, and antidiabetic properties of the aqueous leaf extract of
      Leonotis leonurus (L.) R. BR. (Lamiaceae) in mice and rats, to scientifically
      appraise some of the plant's ethnomedical uses, and its safety and efficacy. The
      leaf powder of the plant was Soxhlet extracted with distilled water and used. The
      antinociceptive effect of the plant's extract was evaluated by the "hot-plate"
      and "acetic acid" test models of pain in mice, while the antiinflammatory and
      antidiabetic effects of the leaf extract were investigated in rats, using fresh
      egg albumin-induced paw edema, and streptozotocin (STZ)-induced diabetes
      mellitus, respectively. Morphine (MPN, 10 mg/kg i.p.), diclofenac (DIC, 100 mg/kg
      i.p.), and chlorpropamide (250 mg/kg p.o.) were used, respectively, as reference
      analgesic, antiinflammatory, and hypoglycemic agents for comparison. L. leonurus
      leaf aqueous extract (LLE, 50-800 mg/kg i.p.) produced dose-dependent and
      significant (p < 0.05-0.001) antinociceptive effects against thermally and
      chemically induced nociceptive pain stimuli in mice. LLE (50-800 mg/kg i.p.) also
      significantly (p < 0.05-0.001) inhibited fresh egg albumin-induced paw edema, and
      caused significant (p < 0.05-0.001) hypoglycemic effects in rats. It is suggested
      that the analgesic effects of LLE (50-800 mg/kg i.p.) may be peripherally and
      centrally mediated. The different flavonoids, diterpenoids, polyphenolics, and
      other chemical constituents of the plant may be involved in the observed
      antinociceptive, antiinflammatory, and antidiabetic effects of the plant's
      extract. However, the results of this experimental animal study suggest that the
      aqueous leaf extract of L. leonurus possesses antinociceptive, antiinflammatory,
      and hypoglycemic properties, and thus lend pharmacological credence to the
      suggested folkloric uses of the herb in the management and/or control of painful,
      arthritic, and other inflammatory conditions, as well as for adult-onset, type-2
      diabetes mellitus in some communities of South Africa.

PMID- 16082427
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials is a guide to the most recent clinical trials in
      current literature and congresses. The data in the following tables have been
      retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the
      drug discovery and development portal, http://integrity.prous.com. This issue
      focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir
      dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab,
      aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4
      MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib,
      bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab
      pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate,
      dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic
      acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium,
      exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux
      sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070,
      imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone;
      Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate,
      neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib
      sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor
      hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin;
      Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride,
      semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole,
      tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol;
      Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid
      monohydrate.

PMID- 16082428
TI  - Preclinical and clinical development of the proteasome inhibitor bortezomib in
      cancer treatment.
AB  - The proteasome is a ubiquitous enzyme complex that plays a critical role in the
      degradation of many proteins involved in cell cycle regulation, apoptosis and
      angiogenesis. Since these pathways are fundamental for cell survival and
      proliferation, particularly in cancer cells, the inhibition of proteasome is an
      attractive potential anticancer therapy. The present review will focus on the
      proteasome inhibitor bortezomib (Velcade, formerly PS-341; Millennium
      Pharmaceuticals, Inc., Cambridge, MA, USA). Bortezomib is an extremely potent and
      selective proteasome inhibitor that shows strong activity in in vitro and in vivo
      laboratory studies against many solid and hematologic tumor types. Moreover,
      bortezomib, mainly by inhibition of the NF-kappaB pathway, has a chemosensitizing
      effect when administered together with other antitumoral drugs. Based on these
      results, bortezomib entered clinical phase I trials, alone or in combination with
      chemotherapy, that showed good tolerance at doses that achieved a desired degree
      of proteasome inhibition. Phase II studies showed high response rates in
      refractory multiple myeloma patients, which led to the accelerated approval of
      bortezomib by the U.S. Food and Drug Administration (FDA) and the European
      Medicines Agency (EMEA) for this indication. A phase III trial comparing
      bortezomib with dexamethasone in refractory/ relapsed multiple myeloma patients
      had to be halted due to a survival advantage in the bortezomib arm. Additional
      studies are focusing on the potential benefit of bortezomib in newly diagnosed
      multiple myeloma patients. In other solid and hematological malignancies, phase
      II studies with bortezomib alone or in combination with other agents are ongoing.
      Encouraging results, particularly in lung cancer and lymphoma, have been
      observed. The critical molecules or genes responsible for tumor sensitivity to
      bortezomib continue to be evaluated using novel technologies.

PMID- 16082429
TI  - Enhanced hypercholesterolemia therapy: the ezetimibe/simvastatin tablet.
AB  - While therapy with HMG-CoA reductase inhibitors, or statins, has provided the
      principal pharmacological innovation in the treatment of hypercholesterolemia in
      recent years, extensive use of these agents has shown that not all patients
      respond to them and that still greater reductions in low-density lipoprotein
      (LDL) cholesterol can further protect patients from cardiovascular events. The
      strategy of increasing the doses of statins is effective but associated with an
      increase in adverse effects. The combination of statins with other agents has
      also, in some cases, increased efficacy, but has likewise been limited by
      toxicity. The administration of a new agent with a novel mechanism of action,
      ezetimibe, with a well-characterized and effective statin, simvastatin, in a
      single tablet now appears to provide enhanced treatment without compromising
      safety. Monotherapy with either ezetimibe or simvastatin has demonstrated the
      ability to significantly lower LDL cholesterol. Simultaneous administration of
      the two agents benefits from their two distinct mechanisms of action: inhibition
      of biliary and dietary cholesterol absorption by ezetimibe and inhibition of
      hepatic cholesterol synthesis by simvastatin. The two mechanisms have exhibited
      complementary activity in preclinical evaluation and have demonstrated an absence
      of pharmacokinetic interaction in humans. Large clinical trials have consistently
      shown that the addition of ezetimibe to simvastatin produces significantly
      greater reductions in LDL cholesterol than simvastatin alone, with tolerability
      similar to statin monotherapy. Ezetimibe/simvastatin has also been associated
      with other beneficial effects on lipids, and it achieves greater efficacy than
      monotherapy with the use of lower, safer doses of the statin. These findings
      indicate that use of the ezetimibe/simvastatin single tablet will allow more
      patients to meet increasingly stringent LDL cholesterol goals, thereby avoiding
      negative cardiovascular outcomes.

PMID- 16082430
TI  - Statins and their roles in cancer.
AB  - The association of long-term statin use with cancer risk has recently become an
      interesting topic because of rather conflicting clinical evidence. On the one
      hand, early animal toxicology studies suggested the carcinogenicity of statins.
      On the other hand, although several large-scale, randomized clinical trials with
      secondary endpoints assessing associated cancer risk confirmed the safety of long
      term statin use, results concerning the risk of specific cancer types remain
      inconclusive. To further complicate matters, retrospective studies concluded that
      the use of statins can actually reduce cancer risk. In addition, several small
      scale cancer trials have shown evidence supporting the use of statins as
      therapeutic anticancer agents. In this review, we will discuss the results of the
      clinical studies, emphasize their strengths and weaknesses, and evaluate their
      potential impact on clinical practice.

PMID- 16082431
TI  - Genetics of bipolar disorder.
AB  - Many linkage loci and candidate genes have been reported in molecular genetic
      studies of bipolar disorder. However, none of these findings have been
      consistently replicated. Meta-analyses of linkage studies have also reported
      conflicting results. Among recently reported candidate genes, BDNF, G72, AKT1,
      GRIN2A, XBP1, GRK3, HTR4, IMPA2 and GABRA1 may have some importance. Study of the
      possible roles of epigenetics or analysis of genetic diseases, in which bipolar
      disorder is one of phenotypes, may also be promising. In addition to
      monoaminergic and intracellular signaling pathways, recent studies have revealed
      possible roles for mitochondrial dysfunction, for glutamatergic dysfunction and
      for the endoplasmic reticulum stress pathway.

PMID- 16082432
TI  - Searching for obesity genes: progress and prospects.
AB  - Obesity is a condition of excess body fat that causes or exacerbates several
      major public health problems. Remarkable progress has been made in the molecular
      elucidation of monogenic forms of obesity both in rodents and in humans. The most
      common form of obesity, however, is considered to be a polygenic disorder arising
      from the interaction of multiple genetic and environmental factors.
      Identification and characterization of susceptibility genes underlying obesity
      will contribute to a greater understanding of the pathogenesis of obesity and
      ultimately will assist in the development of better strategies for prevention and
      therapeutic intervention. In this article, we discuss the current status and
      future perspectives for the genetic dissection of obesity, with a focus on the
      most striking or representative findings.

PMID- 16082433
TI  - Large-vessel vasculitis in a cardiac allograft.

PMID- 16082434
TI  - Morphological and clinical findings in 247 surgically excised native aortic
      valves.
AB  - Aortic valve disease is an increasingly common medical problem in the 20th
      century; however, its pathogenesis is poorly understood. The present paper
      reviews 247 cases of aortic valves surgically excised over a one-year period,
      with special attention to the morphological and histological changes observed in
      surgically excised aortic valves, and to how those changes relate to the
      mechanisms of valve failure. Patient age ranged from 17 to 86 years, with a mean
      of 64.1 +/-13.4 years, and there were 156 men (63.2%) and 91 women (36.8%). A
      total of 172 valves (69.6%) were tricuspid and 75 valves (30.4%) were
      congenitally abnormal, of which 67 valves (27.1%) were congenitally bicuspid, six
      valves (2.4%) were congenitally unicommissural and one valve (0.4%) was
      quadricuspid; the status of one valve could not be determined. Almost 70% of
      patients had features of aortic stenosis. Calcification was seen in the large
      majority of cases, with almost 70% of the valves showing either grade 3 or grade
      4 calcification. Ulceration of calcific nodules was present in 42.0% of cases and
      in the majority of the valves with grade 4 calcification. A total of 15% of the
      valves showed evidence of postinflammatory changes consistent with rheumatic
      disease. Neovascularization was present in two-thirds of all valves, while one
      half showed inflammatory cell infiltrates. Inflammatory cells were composed
      mainly of lymphocytes and macrophages, and were located primarily near areas of
      neovascularization. There was no significant difference in the pathological
      findings between men and women.

PMID- 16082435
TI  - Women have worse long-term outcomes after coronary artery bypass grafting than
      men.
AB  - BACKGROUND: Multiple studies have shown that women have worse in-hospital
      outcomes than men after coronary artery bypass grafting (CABG). The impact of sex
      on long-term results following CABG, however, is not as well established.
      OBJECTIVE: To compare long-term results in men and women undergoing CABG.
      METHODS: A total of 3404 patients underwent isolated CABG between 1995 and 1999
      with follow-up until 2000. Univariate comparisons between men and women were
      carried out based on pre- and intraoperative variables and short- and long-term
      adverse outcomes. Long-term adverse outcomes were defined as all-cause mortality
      or rehospitalization for any cardiac cause, and were risk-adjusted using
      multivariate modelling techniques. RESULTS: Compared with men, women undergoing
      CABG were, on average, older (67.8 years versus 64.2 years), more likely to have
      diabetes (P<0.0001) and hypertension (P<0.0001), and more likely to present for
      surgery with urgent/emergent status (P<0.0001). Intra-operatively, women had
      fewer bypasses (3.0 versus 3.3; P<0.0001) and were less likely to receive a left
      internal mammary artery graft (P=0.0001). While rates of in-hospital mortality
      were comparable between women and men (2.9% versus 2.2%; P=0.22), women were more
      likely to experience a long-term adverse event (30.2% versus 23.5%; P<0.0001).
      After adjusting for clinical differences between men and women, sex emerged as an
      independent predictor of long-term adverse outcomes following CABG (hazard ratio
      = 1.18, P=0.03). CONCLUSIONS: Women presented for CABG with more comorbid
      illness, advanced symptoms and greater urgency than did men. After adjusting for
      differences in clinical presentation, sex emerged as an independent predictor of
      long-term adverse outcomes following CABG.

PMID- 16082436
TI  - Guidelines for the provision of echocardiography in Canada: recommendations of a
      joint Canadian Cardiovascular Society/Canadian Society of Echocardiography
      Consensus Panel.
AB  - Recognizing the central role of echocardiographic examinations in the assessment
      of most cardiac disorders and the need to ensure the provision of these services
      in a highly reliable, timely, economical and safe manner, the Canadian
      Cardiovascular Society and Canadian Society of Echocardiography undertook a
      comprehensive review of all aspects influencing the provision of
      echocardiographic services in Canada. Five regional panels were established to
      develop preliminary recommendations in the five component areas, which included
      the echocardiographic examination, the echocardiographic laboratory and report,
      the physician, the sonographer and indications for examinations. Membership in
      the panels was structured to recognize the regional professional diversity of
      individuals involved in the provision of echocardiography. In addition, a focus
      group of cardiac sonograhers was recruited to review aspects of the document
      impacting on sonographer responsibilities and qualification. The document is
      intended to be used as a comprehensive and practical reference for all of those
      involved in the provision of echocardiography in Canada.

PMID- 16082437
TI  - Moving beyond the cost per quality-adjusted life year: modelling the budgetary
      impact and clinical outcomes associated with the use of sirolimus-eluting stents.
AB  - Restenosis is a major limitation to the long-term success of percutaneous
      coronary intervention. Drug-eluting stents are the most recent technological
      advance in restenosis prevention. While they are effective, their use is
      associated with a significant incremental cost, and a recent economic evaluation
      performed by the authors suggested that their use is associated with a cost per
      quality-adjusted life year of $58,721. How should decision-makers react to this
      value, particularly given that the use of sirolimus-eluting stents appears more
      attractive in certain patient subgroups, such as those with complex coronary
      lesions? In the present paper, the authors explore an alternative method of
      presenting the results of their economic evaluation, rather than the usual cost
      per quality-adjusted life year rubric, in an attempt to assist decision-makers in
      deciding whether, and for whom, to fund sirolimus-eluting stents. Several issues
      that decision-makers and providers may wish to consider when making such funding
      decisions are discussed.

PMID- 16082438
TI  - Device closure of a patent foramen ovale in a patient with lipomatous hypertrophy
      of the atrial septum.
AB  - The presence of a patent foramen ovale has been recognized as a risk factor for
      embolic stroke, and transcatheter device closure of patent foramen ovales is
      increasingly performed to reduce future neurological events. The present report
      discusses a patient who continued to have residual shunting following percutanous
      closure because of improper seating of the device in the presence of a lipomatous
      atrial septum.

PMID- 16082439
TI  - Cardiac arrhythmia due to subclavian catheter fracture and embolization.
AB  - Implanted venous access devices (VADs) are being used with increasing frequency
      in clinical practice. The complication rate is low and VADs are generally
      accepted as being safe. Catheter fracture is a rare but potentially life
      threatening complication that must be recognized and treated promptly. The
      present report discusses a case in which the clinical presentation led to early
      recognition of catheter fracture and embolization, and the subsequent safe
      removal of the VAD.

PMID- 16082440
TI  - Cryopreservation of immature seeds of Ponerorchis graminifolia var. suzukiana by
      vitrification.
AB  - Ponerorchis graminifolia var. suzukiana is a terrestrial orchid that is an
      endangered species native to Japan, and it germinates more readily in immature
      seeds than in mature seeds. To preserve this orchid, an efficient protocol was
      established for the cryopreservation of immature seeds of P. graminifolia var.
      suzukiana. When immature seeds of 6 weeks after pollination, which showed higher
      germination and protocorm formation than mature seeds, were precultured on New
      Dogashima (ND) medium with 0.3M sucrose for 3 days and cryopreserved by
      vitrification method (treated with PVS2 for 60 min), the viability after
      preservation as assessed with 2,3,5-triphenyltetrazolium chloride staining test
      was about 86%. Immature seeds thus treated showed equal rates of germination and
      protocorm formation to the untreated control immature seeds, and they developed
      into normal plantlets on ND medium.

PMID- 16082441
TI  - The effect of cell size distribution on predicted osmotic responses of cells.
AB  - An understanding of the kinetics of the osmotic response of cells is important in
      understanding permeability properties of cell membranes and predicting cell
      responses during exposure to anisotonic conditions. Traditionally, a mathematical
      model of cell osmotic response is obtained by applying mass transport and Boyle
      vant Hoff equations using numerical methods. In the usual application of these
      equations, it is assumed that all cells are the same size equal to the mean or
      mode of the population. However, biological cells (even if they had identical
      membranes and hence identical permeability characteristics--which they do not)
      have a distribution in cell size and will therefore shrink or swell at different
      rates when exposed to anisotonic conditions. A population of cells may therefore
      exhibit a different average osmotic response than that of a single cell. In this
      study, a mathematical model using mass transport and Boyle-van't Hoff equations
      was applied to measured size distributions of cells. Chinese hamster fibroblast
      cells (V-79W) and Madin-Darby canine kidney cells (MDCK), were placed in
      hypertonic solutions and the kinetics of cell shrinkage were monitored.
      Consistent with the theoretical predictions, the size distributions of these
      cells were found to change over time, therefore the selection of the measure of
      central tendency for the population may affect the calculated osmotic parameters.
      After examining three different average volumes (mean, median, and mode) using
      four different theoretical cell size distributions, it was determined that, for
      the assumptions used in this study, the mean or median were the best measures of
      central tendency to describe osmotic volume changes in cell suspensions.

PMID- 16082442
TI  - Cryoprotection in plant tissues related to reduced volume expansion of
      cryoprotectant solution.
AB  - To clarify the mechanism of reduced volume expansion-related cryoprotection
      changes in solution volume during freezing using several types of cryoprotectant
      were investigated. The effect of each cryoprotectant solution on the survival of
      asparagus nodal segments cooled slowly (0.5 degrees C/min) to -40 degrees C was
      also examined. The ratio of the volume at -40 degrees C to the volume at +20
      degrees C was used as an index for expansion, calculated as a ratio of the
      density at +20 degrees C to the density at -40 degrees C. Distilled, deionized
      water showed the largest volume change at a ratio of 1.094. The ratio gradually
      decreased with an increase in the molar concentration of cryoprotectant, with the
      magnitude of the change dependent on the nature of the cryoprotectant. Raffinose
      was the most effective in reducing volume expansion when compared with other
      cryoprotectants at a same concentration. Raffinose exhibited greatest
      cryoprotection in asparagus tissue at 0.6 M where the solution became saturated.
      Dimethyl sulfoxide (Me2SO) at 1.69 M had the largest effect on cryoprotecting
      asparagus tissue. Furthermore, Me2SO was also the most effective in reducing
      volume expansion among the group of cryoprotectants permeable to the plasma
      membrane. It is concluded that cryoprotection in tissues was closely related to
      reduced volume expansion especially at low concentration (< or = 1.0 M).
      Cryoprotectants of impermeable sugar group lost their cryoprotective effect at >
      1.0 M, which may due to severe dehydration and cell damage occurred in hypertonic
      solution. Useful cryoprotectants should be furnished with high ability of
      reducing volume expansion during freezing as well as low toxicity and high
      permeability for cells.

PMID- 16082443
TI  - The assessment of viability in isolated rat hepatocytes subjected to cold or
      subzero non-freezing preservation protocols using a propidium iodide modified
      test.
AB  - A rapid and simple assay (6 min, two steps) is described for determination of
      cell viability of hepatocytes subjected to cold preservation protocols. In this
      method, cells are incubated with the fluorescent marker propidium iodide (PI) and
      the fluorescence intensity is measured before (direct fluorescence--Fd) and after
      (total fluorescence--Ft) addition of digitonin, which allows the dye to enter the
      hepatocytes. The Fd originated from non-viable cells that have membrane damage
      and taken up PI. The Ft originated from all cells in the sample. The ratio
      between the two fluorescence values is used as an indicator of cell viability.
      The assay was challenged versus two classical viability tests: LDH retention and
      Trypan Blue exclusion. Our assay shows good correlation only with Trypan Blue
      test. In addition, a fluorescence confocal microscopy protocol was used to
      evaluate the possible toxicity of PI in hepatocyte suspensions.

PMID- 16082444
TI  - Cryopreservation of embryogenic callus of Aesculus hippocastanum L. by
      vitrification or one-step freezing.
AB  - An effective procedure for the cryopreservation of horse chestnut (Aesculus
      hippocastanum L.) embryogenic callus by vitrification/one-step freezing is
      described here. In particular, the study focused on the possibility of recovering
      the full proliferation potential of the embryogenic lines after storage in liquid
      nitrogen. The developmental stage of the embryogenic lines was shown to play an
      important role. Ninety-min incubation in PVS2 and preservation at -196 degrees C
      of callus samples, containing a prevalence of embryogenic masses at an advanced
      stage of somatic embryo maturation (i.e., the torpedo stage), gave optimum
      regrowth of healthy and proliferating embryogenic callus. Moreover, raising the
      thawing temperature to 45 degrees C yielded the maximum survival (94%) of torpedo
      stage embryogenic samples, recovery of proliferation and, in more than 70% of
      cases, maturation to the cotyledonary stage. This study opens the way to the
      possibility of safe, long-term storage in liquid nitrogen of valuable embryogenic
      lines of horse chestnut, avoiding repeated subculturing.

PMID- 16082445
TI  - Morphology study of freeze-drying mononuclear cells of human cord blood.
AB  - The research on haematopoietic stem cells of human cord blood has become more
      important recently. At present, cord blood is mainly preserved at ultra-low
      temperatures. In the former study, we compared the effects of preserving
      mononuclear cells (MNC) and whole human cord blood by freeze-drying. This time, a
      further study was conducted on freeze-drying mononuclear cells. Samples in the
      presence of PVP, sucrose, mannitol and FBS were firstly frozen to -38 degrees C.
      Afterwards, they were vacuum-dried at a selected shelf temperature of -30 degrees
      C for the main drying stage, and then vacuum-dried at 15 degrees C for the second
      drying stage. The entire time of freeze-drying process was 41 hours. Samples were
      stored at room temperature for 7 days prior to evaluation. Subsequently, the
      dried samples were resuspended in an isotonic phosphate-buffered saline solution.
      The residual moisture content was 6.5 +/- 0.87%. The recovery of the cells was
      tested by a haemacytometer, and the numerical cell count recovery of rehydrated
      MNC increased by 8%. Morphology of the fresh and rehydrated MNC was analyzed
      respectively using standard light microscopy, scanning electron microscope and
      transmission electron microscope. The results showed that karyons changed and
      cytoplasm decreased after rehydration, but it is still unknown that whether these
      changes will influence the proliferative ability of the stem cells.

PMID- 16082446
TI  - Comparison of cryopreservation techniques for long-term storage of ash (Fraxinus
      excelsior L.).
AB  - The main purpose of this study was to develop a cryopreservation protocol for ash
      and to highlight the importance of testing different clones and plant material of
      different ontogenetic states. In vitro-grown ash (Fraxinus excelsior L.) shoot
      tips were successfully cryopreserved following optimization of the PVS2
      vitrification protocol. Pretreatment conditions were optimized and three
      cryopreservation techniques (encapsulation/dehydration, PVS2-vitrification and
      encapsulation-vitrification) were tested one after another. PVS2-vitrification
      proved to be the most suitable technique. In vitro-grown shoot tips of ash were
      successfully cryopreserved with a mean regrowth of 73% for juvenile clones and
      67% for selected mature trees. The optimum preculture conditions and the initial
      protocol were: 10 days cold hardening, preculture for 2 days on medium with 0.8 M
      glycerol, incubation in 2 M glycerol solution for 20 min at 22 degrees C followed
      by PVS2 for 25 min at 0 degrees C on ice and direct immersion in liquid nitrogen.
      Warming was carried out in 43 degree C water for 1 min followed by 22 degree C
      water for 10 sec. The encapsulation/dehydration method was not successful for
      shoot tips of F. excelsior because the shoots were sensitive to osmotic
      dehydration. The encapsulation/vitrification method resulted in a mean regrowth
      of only 16%. PVS2 vitrification can now be used to store important ash germplasm
      of either juvenile or mature trees.

PMID- 16082448
TI  - [Sleep promoters and insomnia].
AB  - The purpose of this updating manuscript is to briefly describe the profile,
      clinical use and indication of some of the most used sedative and hypnotic
      compounds. About 2/3 of all hypnotic prescriptions go to chronic use.
      Benzodiazepines are among the most prescribed drugs worldwide. Women, elderly,
      psychiatric and medical disease patients are among chronic users of hypnotics.
      Zolpidem is now the most prescribed hypnotic in most countries. It appears to be
      safer, compared to benzodazepines, and might be an option for long-term and
      controlled use ("as needed"). Sedative antidepressants are also among the most
      prescribed drug for sedation in insomnia patients in USA and UK. Sedative effect
      and use of trazodone, mirtazapine, doxepine, amitryptilin are described. The
      authors also discuss the use of melatonin and its sleep properties, and the
      rational use of sedative antipsychotics for chronic insomnia, particularly in
      psychiatric patients. Finally, some phytotherapeutic compounds are mentioned.

PMID- 16082449
TI  - [Diagnostics methods for sleep disorders].
AB  - The aim of this manuscript is to describe the procedures, recommendations,
      findings and value of the diagnostic methods used in Sleep Disorders including
      questionnaires, Actigraph, Polysomnography and Multiple sleep latency test.
      Specific questionnaires including evaluation of sleep quality , hyper somnolence,
      Respiratory Sleep Disorders and Sleep-Wake rhythm are in general, used as a
      screening for the Sleep Disorders and indication of sleep studies. Polysomnogram
      and Multiple sleep latency test are considered the gold standard methods for the
      diagnosis of majority of sleep disorders and Narcolepsy respectively. Criteria
      for these disorders are reported below.

PMID- 16082450
TI  - [Excessive daytime sleepiness].
AB  - Sleepiness is a physiological function, and can be defined as increased
      propension to fall asleep. However, excessive sleepiness (ES) or hypersomnia
      refer to an abnormal increase in the probability to fall asleep, to take
      involuntary naps, or to have sleep atacks, when sleep is not desired. The main
      causes of excessive sleepiness is chronic sleep deprivation, sleep apnea
      syndrome, narcolepsy, movement disorders during sleep, circadian sleep disorders,
      use of drugs and medications, or idiopathic hypersomnia. Social, familial, work,
      and cognitive impairment are among the consequences of hypersomnia. Moreover, it
      has also been reported increased risk of accidents. The treatment of excessive
      sleepiness includes treating the primary cause, whenever identified. Sleep
      hygiene for sleep deprivation, positive pressure (CPAP) for sleep apnea,
      dopaminergic agents and exercises for sleep-related movement disorders,
      phototherapy and/or melatonin for circadian disorders, and use of stimulants are
      the treatment modalities of first choice.

PMID- 16082451
TI  - [Violent behavior during sleep].
AB  - Cases of violent behavior during sleep have been reported in the literature.
      However, the incidence of violent behavior during sleep is not known. One
      epidemiological study showed that approximately 2% of the general population,
      predominantly males, presented violent behavior while asleep. In the present
      study, the authors describe clinical and medico-legal aspects involved in violent
      behavior investigation. Violent behavior refers to self-injury or injury to
      another during sleep. It happens most frequently following partial awakening in
      the context of arousal disorders (parasomnias). The most frequently diagnosed
      sleep disorders are REM behavior disorder and somnambulism. Violent behavior
      might be precipitated by stress, use of alcohol or drugs, sleep deprivation or
      fever.

PMID- 16082452
TI  - [Sleep in psychiatric disorders].
AB  - Altered sleep patterns are prominent in the majority of psychiatric disorders.
      This article examines the psychiatric disorders that are most often associated to
      sleep dysfunction as it is related in clinical practice and describes the
      polysomnographic findings. Patient's main complaints are related to difficulty in
      initiating and maintaining sleep (initial or middle insomnia, respectively) and
      poor quality of sleep. Early awakening or terminal insomnia is most described in
      the depressive conditions. Hypersomnia may be the main symptom in some depressive
      disorders, as seasonal depression, depression with atypical features or
      depressive episodes in bipolar disorder. Polysomnographic evaluation shows, in
      general, a significative reduction in the efficiency and total time of sleep, in
      detriment to the amount of slow wave sleep. The reduction of rapid eye movement
      (REM) sleep latency is mainly described for the depression, but has also been
      reported in other psychiatric disorders.

PMID- 16082453
TI  - [Sleep-wake cycle mechanisms].
AB  - Neurochemically distinct systems interact regulating sleep and wakefulness.
      Wakefulness is promoted by aminergic, acetylcholinergic brainstem and
      hypothalamic systems. Each of these arousal systems supports wakefulness and
      coordinated activity is required for alertness and EEG activation. Neurons in the
      pons and preoptic area control rapid eye movement and non-rapid eye movement
      sleep. Mutual inhibition between these wake- and sleep-regulating systems
      generate behavioral states. An up-to-date understanding of these systems should
      allow clinicians and researchers to better understand the effects of drugs,
      lesions, and neurologic disease on sleep and wakefulness.

PMID- 16082454
TI  - Highlights of the 3rd International Conference on High Pressure Bioscience and
      Biotechnology.
AB  - The 3rd International Conference on High Pressure Bioscience and Biotechnology
      was held in the city of Rio de Janeiro from September 27 to September 30, 2004.
      The meeting, promoted by the International Association of High Pressure
      Bioscience and Biotechnology (IAHPBB), congregated top scientists and researchers
      from all over the world. In common, they shared the use of hydrostatic pressure
      for research, technical development, or industrial applications. The meeting
      consisted of invited lectures, contributed papers and a well-attended poster
      session. Very exciting discussions were held inside and outside the sessions, and
      the goals of discussing state-of-the-art data and establishing working
      collaborations and co-operations were fully attained.

PMID- 16082455
TI  - Protein dynamics: hydration and cavities.
AB  - The temperature-pressure behavior of proteins seems to be unique among the
      biological macromolecules. Thermodynamic as well as kinetic data show the typical
      elliptical stability diagram. This may be extended by assuming that the unfolded
      state gives rise to volume and enthalpy-driven liquid-liquid transitions. A
      molecular interpretation follows from the temperature and the pressure dependence
      of the hydration and cavities. We suggest that positron annihilation spectroscopy
      can provide additional quantitative evidence for the contributions of cavities to
      the dynamics of proteins. Only mature amyloid fibrils that form from unfolded
      proteins are very resistant to pressure treatment.

PMID- 16082456
TI  - Insights into the role of hydration in protein structure and stability obtained
      through hydrostatic pressure studies.
AB  - A thorough understanding of protein structure and stability requires that we
      elucidate the molecular basis for the effects of both temperature and pressure on
      protein conformational transitions. While temperature effects are relatively well
      understood and the change in heat capacity upon unfolding has been reasonably
      well parameterized, the state of understanding of pressure effects is much less
      advanced. Ultimately, a quantitative parameterization of the volume changes (at
      the basis of pressure effects) accompanying protein conformational transitions
      will be required. The present report introduces a qualitative hypothesis based on
      available model compound data for the molecular basis of volume change upon
      protein unfolding and its dependence on temperature.

PMID- 16082457
TI  - The powerful high pressure tool for protein conformational studies.
AB  - The pressure behavior of proteins may be summarized as a the pressure-induced
      disordering of their structures. This thermodynamic parameter has effects on
      proteins that are similar but not identical to those induced by temperature, the
      other thermodynamic parameter. Of particular importance are the intermolecular
      interactions that follow partial protein unfolding and that give rise to the
      formation of fibrils. Because some proteins do not form fibrils under pressure,
      these observations can be related to the shape of the stability diagram. Weak
      interactions which are differently affected by hydrostatic pressure or
      temperature play a determinant role in protein stability. Pressure acts on the 2
      degrees, 3 degrees and 4 degrees structures of proteins which are maintained by
      electrostatic and hydrophobic interactions and by hydrogen bonds. We present some
      typical examples of how pressure affects the tertiary structure of proteins (the
      case of prion proteins), induces unfolding (ataxin), is a convenient tool to
      study enzyme dissociation (enolase), and provides arguments to understand the
      role of the partial volume of an enzyme (butyrylcholinesterase). This approach
      may have important implications for the understanding of the basic mechanism of
      protein diseases and for the development of preventive and therapeutic measures.

PMID- 16082458
TI  - Pressure-assisted cold denaturation of hen egg white lysozyme: the influence of
      co-solvents probed by hydrogen exchange nuclear magnetic resonance.
AB  - COSY proton nuclear magnetic resonance was used to measure the exchange rates of
      amide protons of hen egg white lysozyme (HEWL) in the pressure-assisted cold
      denatured state and in the heat-denatured state. After dissolving lysozyme in
      deuterium oxide buffer, labile protons exchange for deuterons in such a way that
      exposed protons are substituted rapidly, whereas "protected" protons within
      structured parts of the protein are substituted slowly. The exchange rates k obs
      were determined for HEWL under heat treatment (80 degrees C) and under high
      pressure conditions at low temperature (3.75 kbar, -13 degrees C). Moreover, the
      influence of co-solvents (sorbitol, urea) on the exchange rate was examined under
      pressure-assisted cold denaturation conditions, and the corresponding protection
      factors, P, were determined. The exchange kinetics upon heat treatment was found
      to be a two-step process with initial slow exchange followed by a fast one,
      showing residual protection in the slow-exchange state and P-factors in the
      random-coil-like range for the final temperature-denatured state. Addition of
      sorbitol (500 mM) led to an increase of P-factors for the pressure-assisted cold
      denatured state, but not for the heat-denatured state. The presence of 2 M urea
      resulted in a drastic decrease of the P-factors of the pressure-assisted cold
      denatured state. For both types of co-solvents, the effect they exert appears to
      be cooperative, i.e., no particular regions within the protein can be identified
      with significantly diverse changes of P-factors.

PMID- 16082459
TI  - Volume and energy folding landscape of prion protein revealed by pressure.
AB  - The main hypothesis for prion diseases proposes that the cellular protein (PrP C)
      can be altered into a misfolded, ss-sheet-rich isoform, the PrP Sc (from
      scrapie). The formation of this abnormal isoform then triggers the transmissible
      spongiform encephalopathies. Here, we discuss the use of high pressure as a tool
      to investigate this structural transition and to populate possible intermediates
      in the folding/unfolding pathway of the prion protein. The latest findings on the
      application of high pressure to the cellular prion protein and to the scrapie PrP
      forms will be summarized in this review, which focuses on the energetic and
      volumetric properties of prion folding and conversion.

PMID- 16082460
TI  - The effect of hydrostatic pressure on membrane-bound proteins.
AB  - Many cellular proteins are bound to the surfaces of membranes and participate in
      various cell signaling responses. Interactions between this group of proteins are
      in part controlled by the membrane surface to which the proteins are bound. This
      review focuses on the effects of pressure on membrane-associated proteins.
      Initially, the effect of pressure on membrane surfaces and how pressure may
      perturb the membrane binding of proteins is discussed. Next, the effect of
      pressure on the activity and lateral association of proteins is considered. We
      then discuss how pressure can be used to gain insight into these types of
      proteins.

PMID- 16082461
TI  - Pressure-induced dissociation of casein micelles: size distribution and effect of
      temperature.
AB  - Pressure-induced dissociation of a turbid solution of casein micelles was studied
      in situ in static and dynamic light scattering experiments. We show that at high
      pressure casein micelles decompose into small fragments comparable in size to
      casein monomers. At intermediate pressure we observe particles measuring 15 to 20
      nm in diameter. The stability against pressure dissociation increased with
      temperature, suggesting enhanced hydrophobic contacts. The pressure transition
      curves are biphasic, compatible with a temperature (but not pressure)-dependent
      conformational equilibrium of two micelle species. Our thermodynamic model
      predicts an increase in structural entropy with temperature.

PMID- 16082462
TI  - Stabilization of partially folded states in protein folding/misfolding
      transitions by hydrostatic pressure.
AB  - In the last few years, hydrostatic pressure has been extensively used in the
      study of both protein folding and misfolding/aggregation. Compared to other
      chemical or physical denaturing agents, a unique feature of pressure is its
      ability to induce subtle changes in protein conformation, which allow the
      stabilization of partially folded intermediate states that are usually not
      significantly populated under more drastic conditions (e.g., in the presence of
      chemical denaturants or at high temperatures). Much of the recent research in the
      field of protein folding has focused on the characterization of folding
      intermediates since these species appear to be involved in a variety of disease
      causing protein misfolding and aggregation events. The exact mechanisms of these
      biological phenomena, however, are still poorly understood. Here, we review
      recent examples of the use of hydrostatic pressure as a tool to obtain insight
      into the forces and energetics governing the productive folding or the misfolding
      and aggregation of proteins.

PMID- 16082463
TI  - Some physico-chemical parameters that influence proteinase K resistance and the
      infectivity of PrPSc after high pressure treatment.
AB  - Crude brain homogenates of terminally diseased hamsters infected with the 263 K
      strain of scrapie (PrP Sc) were heated and/or pressurized at 800 MPa at 60
      degrees C for different times (a few seconds or 5, 30, 120 min) in phosphate
      buffered saline (PBS) of different pH and concentration. Prion proteins were
      analyzed on immunoblots for their proteinase K (PK) resistance, and in hamster
      bioassays for their infectivity. Samples pressurized under initially neutral
      conditions and containing native PrP Sc were negative on immunoblots after PK
      treatment, and a 6-7 log reduction of infectious units per gram was found when
      the samples were pressurized in PBS of pH 7.4 for 2 h. A pressure-induced change
      in the protein conformation of native PrP Sc may lead to less PK resistant and
      less infectious prions. However, opposite results were obtained after
      pressurizing native infectious prions at slightly acidic pH and in PBS of higher
      concentration. In this case an extensive fraction of native PrP Sc remained PK
      resistant after pressure treatment, indicating a protective effect possibly due
      to induced aggregation of prion proteins in such buffers.

PMID- 16082464
TI  - Differences in pressure and temperature transitions of proteins and polymer gels.
AB  - Pressure-driven and temperature-driven transitions of two thermoresponsive
      polymers, poly(N-isopropylacrylamide) (pNIPAM) and poly(N-vinylisobutyramide)
      (pNVIBA)), in both a soluble linear polymer form and a cross-linked hydro-gel
      form, were examined by a dynamic light-scattering method and direct microscopic
      observation, respectively. Their behavior was compared with that of protein
      systems. Changes in some characteristic parameters in the time-intensity
      correlation functions of dynamic light-scattering measurement of aqueous
      solutions of pNIPAM at various pressures and temperatures showed no essential
      differences during temperature and pressure scanning and, as a whole, the motions
      of polymers in aqueous solutions were similar in two types of transitions until
      chain shrinkage occurred. The gels (cross-linked polymer gels) prepared from the
      thermoresponsive polymers also showed similar volume transitions responding to
      the pressure and temperature increase. In temperature transitions, however, gels
      showed drastic volume shrinkage with loss of transparency, while pressure-induced
      transition showed a slow recovery of transparency while keeping the size, after
      first transient drastic volume shrinkage with loss of transparency. At a
      temperature slightly higher than the transition under atmospheric temperature, so
      called reentry of the volume change and recovery of the transparency were
      observed during the pressure-increasing process, which implies much smaller
      aggregation or non-aggregated collapsed polymer chains in the gel at higher
      pressures, indicating a certain mechanistic difference of the dehydration
      processes induced by temperature and pressure.

PMID- 16082465
TI  - How does yeast respond to pressure?
AB  - The brewing and baking yeast Saccharomyces cerevisiae has been used as a model
      for stress response studies of eukaryotic cells. In this review we focus on the
      effect of high hydrostatic pressure (HHP) on S. cerevisiae. HHP exerts a broad
      effect on yeast cells characteristic of common stresses, mainly associated with
      protein alteration and lipid bilayer phase transition. Like most stresses,
      pressure induces cell cycle arrest. Below 50 MPa (500 atm) yeast cell morphology
      is unaffected whereas above 220 MPa wild-type cells are killed. S. cerevisiae
      cells can acquire barotolerance if they are pretreated with a sublethal stress
      due to temperature, ethanol, hydrogen peroxide, or pressure. Nevertheless,
      pressure only leads to protection against severe stress if, after pressure
      pretreatment, the cells are also re-incubated at room pressure. We attribute this
      effect to the inhibition of the protein synthesis apparatus under HHP. The global
      genome expression analysis of S. cerevisiae cells submitted to HHP revealed a
      stress response profile. The majority of the up-regulated genes are involved in
      stress defense and carbohydrate metabolism while most repressed genes belong to
      the cell cycle progression and protein synthesis categories. However, the
      signaling pathway involved in the pressure response is still to be elucidated.
      Nitric oxide, a signaling molecule involved in the regulation of a large number
      of cellular functions, confers baroprotection. Furthermore, S. cerevisiae cells
      in the early exponential phase submitted to 50-MPa pressure show induction of the
      expression level of the nitric oxide synthase inducible isoform. As pressure
      becomes an important biotechnological tool, studies concerning this kind of
      stress in microorganisms are imperative.

PMID- 16082466
TI  - High pressure-sensitive gene expression in Lactobacillus sanfranciscensis.
AB  - Lactobacillus sanfranciscensis is a Gram-positive lactic acid bacterium used in
      food biotechnology. It is necessary to investigate many aspects of a model
      organism to elucidate mechanisms of stress response, to facilitate preparation,
      application and performance in food fermentation, to understand mechanisms of
      inactivation, and to identify novel tools for high pressure biotechnology. To
      investigate the mechanisms of the complex bacterial response to high pressure we
      have analyzed changes in the proteome and transcriptome by 2-D electrophoresis,
      and by microarrays and real time PCR, respectively. More than 16 proteins were
      found to be differentially expressed upon high pressure stress and were compared
      to those sensitive to other stresses. Except for one apparently high pressure
      specific stress protein, no pressure-specific stress proteins were found, and the
      proteome response to pressure was found to differ from that induced by other
      stresses. Selected pressure-sensitive proteins were partially sequenced and their
      genes were identified by reverse genetics. In a transcriptome analysis of a
      redundancy cleared shot gun library, about 7% of the genes investigated were
      found to be affected. Most of them appeared to be up-regulated 2- to 4-fold and
      these results were confirmed by real time PCR. Gene induction was shown for some
      genes up-regulated at the proteome level (clpL/groEL/rbsK), while the response of
      others to high hydrostatic pressure at the transcriptome level seemed to differ
      from that observed at the proteome level. The up-regulation of selected genes
      supports the view that the cell tries to compensate for pressure-induced
      impairment of translation and membrane transport.

PMID- 16082467
TI  - Modeling the pressure inactivation dynamics of Escherichia coli.
AB  - Escherichia coli, as a model microorganism, was treated in phosphate-buffered
      saline under high hydrostatic pressure between 100 and 300 MPa, and the
      inactivation dynamics was investigated from the viewpoint of predictive
      microbiology. Inactivation data were curve fitted by typical predictive models:
      logistic, Gompertz and Weibull functions. Weibull function described the
      inactivation curve the best. Two parameters of Weibull function were calculated
      for each holding pressure and their dependence on holding pressure was obtained
      by interpolation. With the interpolated parameters, inactivation curves were
      simulated and compared with the experimental data sets.

PMID- 16082468
TI  - Inactivation of Staphylococcus aureus and Salmonella enteritidis in tryptic soy
      broth and caviar samples by high pressure processing.
AB  - We studied the action of high pressure processing on the inactivation of two
      foodborne pathogens, Staphylococcus aureus ATCC 6538 and Salmonella enteritidis
      ATCC 13076, suspended in a culture medium and inoculated into caviar samples. The
      baroresistance of the two pathogens in a tryptic soy broth suspension at a
      concentration of 10(8)-10(9) colony-forming units/ml was tested for continuous
      and cycled pressurization in the 150- to 550-MPa range and for 15-min treatments
      at room temperature. The increase of cycle number permitted the reduction of the
      pressure level able to totally inactivate both microorganisms in the tryptic soy
      broth suspension, whereas the effect of different procedure times on complete
      inactivation of the microorganisms inoculated into caviar was similar.

PMID- 16082469
TI  - The biological effects of high-pressure gas on the yeast transcriptome.
AB  - The aim of the present study was to examine the feasibility of DNA microarray
      technology in an attempt to construct an evaluation system for determining gas
      toxicity using high-pressure conditions, as it is well known that pressure
      increases the concentration of a gas. As a first step, we used yeast
      (Saccharomyces cerevisiae) as the indicator organism and analyzed the mRNA
      expression profiles after exposure of yeast cells to nitrogen gas. Nitrogen gas
      was selected as a negative control since this gas has low toxicity. Yeast DNA
      microarray analysis revealed induction of genes whose products were localized to
      the membranes, and of genes that are involved in or contribute to energy
      production. Furthermore, we found that nitrogen gas significantly affected the
      transport system in the cells. Interestingly, nitrogen gas also resulted in
      induction of cold-shock responsive genes. These results suggest the possibility
      of applying yeast DNA microarray to gas bioassays up to 40 MPa. We therefore
      think that "bioassays" are ideal for use in environmental control and protection
      studies.

PMID- 16082470
TI  - High pressure near infrared study of the mutated light-harvesting complex LH2.
AB  - The pressure sensitivities of the near infrared spectra of the light-harvesting
      (LH2) complex and a mutant complex with a simplified BChl-B850 binding pocket
      were compared. In the mutant an abrupt change in the spectral properties occurred
      at 250 MPa, which was not observed with the native sample. Increased disorder due
      to collapse of the chromophore pocket is suggested.

PMID- 16082471
TI  - Effect of high hydrostatic pressure on the barrier properties of polyamide-6
      films.
AB  - Little is known about the barrier properties of polymer films during high
      pressure processing of prepackaged foods. In order to learn more about this, we
      examined the influence of high hydrostatic pressure on the permeation of
      raspberry ketone (dissolved in ethanol/water) through polyamide-6 films at
      temperatures between 20 and 60 degrees C. Permeation was lowered by increasing
      pressure at all temperatures. At 23 degrees C, the increasing pressure sequence
      0.1, 50, 100, 150, and 200 MPa correlated with the decreasing permeation
      coefficients P/(10(9) cm(2) s-1) of 6.2, 3.8, 3.0, 2.2, and 1.6. Analysis of the
      permeation kinetics indicated that this effect was due to a reduced diffusion
      coefficient. Pressure and temperature acted antagonistically to each other. The
      decrease in permeation at 200 MPa was compensated for by a temperature increase
      of 20 degrees C. After release of pressure, the former permeation coefficients
      were recovered, which suggests that this 'pressure effect' is reversible. Taken
      together, our data revealed no detrimental effects of high hydrostatic pressure
      on the barrier properties of polymer films.

PMID- 16082472
TI  - Prevalence of anti-hepatits A antibodies in children of different socioeconomic
      conditions in Vila Velha, ES.
AB  - This report describes the prevalence of anti-HAV antibodies in children from
      elementary school in the Municipality of Vila Velha, ES, Brazil. Anti-HAV
      antibodies were investigated by ELISA method in the serum of 606 children (four
      to fourteen years old) from three elementary schools, located in neighborhoods
      with varying household monthly income levels: Sao Jose School, 200 children,
      household income higher than US$700; Sao Torquato School, 273 children, US$200 to
      300; and Cobi School, 133 children, less than US$200. From each children data on
      age, gender, skin color, sanitary conditions, frequency of contact with sea or
      river water and family history of hepatitis were recorded. Anti-HAV antibodies
      were present in 38.6% of all children, 9% in Sao Jose School, 49.1% in Sao
      Torquato School and 61.7% in Cobi School. Logistic regression analysis
      demonstrated a positive correlation of positive anti-HAV test with age, non white
      color of the skin, absence of sewage treatment and domestic water filter, and a
      past history of hepatitis. The prevalence of anti-HAV antibodies in school
      children in Vila Velha, ES, was lower than that observed in the same age group in
      North and Northeast Brazil and was significantly higher in children from families
      with low socioeconomic status. In addition the results indicate a changing
      epidemiologic pattern of hepatitis A in our country, with an increasing number of
      children and adolescents with high risk for HAV infection, mainly in high
      socioeconomic class. A consideration must be given to the feasibility of
      vaccination programs for children and adolescents in our country.

PMID- 16082473
TI  - Very low prevalence of hepatitis C virus infection in rural communities of
      northeastern Brazil with a high prevalence of schistosomiasis mansoni.
AB  - The association of hepatitis C virus infection and the hepatosplenic form of
      schistosomiasis mansoni has been claimed to result in the concomitant evolution
      of the two pathologies, with a poor prognosis due to aggravated liver disease.
      Recently, however, some authors have begun to reject the hypothesis of a higher
      susceptibility of hepatosplenic schistosomal patients to HCV. The aim of the
      present transverse study carried out between July and August 1990 was to
      determine the possible association between SM and HCV markers in residents of
      Catolandia, Bahia State. Anti-HCV markers were assayed by ELISA-II and RIBA-II in
      serum samples obtained from 1,228 residents (85.8%). The anti-HCV antibody (ELISA
      II) was positive in six (0.5%) individuals, eight (0.6%) cases were inconclusive
      and 1,214 (98.9%) were negative. However, only in one ELISA-positive serum sample
      (0.08%) were antibodies confirmed by RIBA-II, while two other samples assayed by
      RIBA-II were indeterminate. These three patients presented the hepatointestinal
      form of SM during the follow-up period (1976 to 1996). In conclusion, no
      association was observed between HCV and SM in the endemic area studied,
      especially among patients with the hepatosplenic form of the disease.

PMID- 16082474
TI  - [Evidence of dog as a reservoir for human leptospirosis: a serovar isolation,
      molecular characterization and its use in a serological survey].
AB  - Canine leptospirosis has been known as Stuttgart disease since 1898, and dogs are
      considered to be the second principal source of infection in man. The isolation
      of a pathogenic serovar from dog urine that was diagnosed clinically and
      laboratorial as having leptospirosis and its utilization to test serological
      samples of human and canine cases of leptospirosis, has demonstrated its
      importance to the ecosystem of the southern region of Brazil. The results of the
      serological microscopic agglutination test indicated that 100% of human serum
      samples from 12 patients from the serum bank of 2001 at the Center for Control of
      Zoonoses, that had titers between 25 and 3,200 with the canicola serovar, and 72%
      of 105 canine serum samples from the same serum bank, also reacted with the new
      isolate. The mean and median titers of the human serum samples tested with the
      battery of antigens recommended by WHO was 630 and 100 respectively, and when
      tested with the isolate it was 1,823 and 400. In the dog sera, the values were
      respectively 347 and 100 with the battery, and 1,088 and 200 with the isolate.

PMID- 16082475
TI  - [Schistosomiasis mansoni in two mesoregions of the State of Alagoas].
AB  - In Brazil, high levels of schistosomiasis mansoni are linked to the presence of
      the species Biomphalaria glabrata, considered to be the main host of Schistosoma
      mansoni in endemic areas. This work conducted a survey of 40 endemic
      municipalities in the State of Alagoas, aiming at identifying this species and
      its important role in the maintenance of schistosomiasis. Among the
      municipalities surveyed, 28 lie in the mesoregion of the Leste Alagoano and 12,
      in the mesoregion of the Agreste Alagoano. The snails collected for analysis came
      from different types of habitats, namely streams, springs, ditches, dams, swamps,
      wells and ponds. The snails were collected from February 1996 through December
      1998. The identification of Biomphalaria glabrata was made through anatomical
      analysis of the soft inner parts of the snails after having removed their shells.
      As for the detection of cercariae of Schistosoma mansoni, the crush technique was
      applied in order to calculate the percentage of infection rates. Among the areas
      surveyed, 32 municipalities (80% of the total), presented the species
      Biomphalaria glabrata, six of which containing snails infected with cercariae of
      the parasite. Penedo presented the highest infection rate (6.6%), followed by
      Ibateguara (5.6%). Lower rates were noticed in Cha Preta (2.7%), in Murici
      (2.5%), Porto Real do Colegio (0.1%) and Igreja Nova (0.1%). The
      coproparasitologic analyses conducted at the Fundacao Nacional de Saude in 1997,
      1998/1999 and 2000, confirmed the importance of schistosomiasis mansoni in the
      areas surveyed in this work.

PMID- 16082476
TI  - [Features of Chagas' disease patients with emphasis on digestive form, in a
      tertiary hospital of Ribeirao Preto, SP].
AB  - In order to characterize the demographic and clinical profile of patients with
      digestive manifestations of Chagas' disease, the medical records were reviewed of
      patients (n = 377) currently attended at Hospital das Clinicas da Faculdade de
      Medicina de Ribeirao Preto with positive serologic reaction for Chagas' disease
      and admitted from January 2002 to March 2003. Median age was 67 years and 210
      (56%) were women. Megaesophagus and/or megacolon were present in 135 patients,
      59% of these had cardiopathy. For 49% of patients with digestive disease, at
      least two medical prescriptions of medicines for the treatment of cardiovascular
      diseases were found. In 66 patients, chronic comorbidities were detected. The
      population with digestive manifestation of Chagas' disease referred to HCFMRP is
      mostly geriatric, with an elevated frequency of cardiopathy, which may indicate a
      high risk for surgical approach to the treatment of chagasic megaesophagus and
      megacolon.

PMID- 16082477
TI  - Longitudinal clinical and serological survey of abdominal angiostrongyliasis in
      Guapore, southern Brazil, from 1995 to 1999.
AB  - Abdominal angiostrongyliasis is a zoonotic infection caused by Angiostrongylus
      costaricensis, a nematode with an intra-vascular location in the mesentery. Our
      objective was to address several aspects of the natural history of this
      parasitosis, in a longitudinal clinical and seroepidemiological study. A total of
      179 individuals living in a rural area with active transmission in southern
      Brazil were followed for five years (1995-1999) resulting in yearly prevalence of
      28.2%, 4.2%, 10%, 20.2% and 2.8% and incidences of 0%, 5.9%, 8% and 1.5%,
      respectively. Both men and woman were affected with higher frequencies at age 30
      49 years. In 32 individuals serum samples were collected at all time points and
      IgG antibody reactivity detected by ELISA was variable and usually persisting not
      longer than one year. Some individual antibody patterns were suggestive of re
      infection. There was no association with occurrence of abdominal pain or of other
      enteroparasites and there was no individual with a confirmed (histopathologic)
      diagnosis. Mollusks were found with infective third-stage larvae in some houses
      with an overall prevalence of 16% and a low parasitic burden. In conclusion,
      abdominal angiostrongyliasis in southern Brazil may be a frequent infection with
      low morbidity and a gradually decreasing serological reactivity.

PMID- 16082478
TI  - [Residual effect of commercial applications of larvicides temefos and Bacillus
      thuringiensis israelensis on Aedes aegypti larvae in recipients with water
      renewal].
AB  - The residual effect of temefos (commercial applications A, B and C) and Bacillus
      thuringiensis israelensis (D and E) on Aedes aegypti larvae was evaluated, in
      recipients with water renewal. Forty-four beakers of 1,000ml each (8 for each
      application and 4 controls) were used. In each beaker, 25 larvae were introduced
      daily. After 24 hours, the dead larvae were counted, the beakers emptied to 200ml
      and refilled to original volume, with addition of new larvae. The duration of the
      maximum residual effect (100% of mortality) was: A-19; B-39; C-40; D-8; E-19
      days. The mortality ratio of all applications remained equivalent for 25 days; B,
      C and E maintained MR equivalent up to 45 days; B and C showed MR 2.40 times
      greater than E, between 46-95 days; B, compared with A, showed MR 1.90-7.51 times
      greater between 26-95 days. The conclusion was greater effectiveness of two
      presentations of temefos, even in an epidemiological situation with long exposure
      to the product and renewal of water in recipients.

PMID- 16082479
TI  - [Helicobacter pylori identification by brush gastric cytology: a comparison with
      histologic method].
AB  - The purpose of this study was to verify the efficacy of brush gastric cytology
      for diagnosis of Helicobacter pylori infection in patients, submitted to elective
      gastroscopy, compared to the method of endoscopic histology. Endoscopy was
      performed on 157 patients, divided into two dyspeptic groups: group A (n = 27)
      with duodenal ulcer; and group B (n = 130) without ulcer. In group A, the
      percentage of positive cases detected by brush cytology (77.8%) was similar to
      histology (74.1%; p = 0.3). While in group B, brush cytology (71.5%) was superior
      to histology (63.1%; p = 0.00002). Brush cytology is a simple and useful
      diagnostic method. It was efficient for identification of Helicobacter pylori
      infection in both groups.

PMID- 16082480
TI  - Retrospective study of the occurrence of Cyclospora cayetanensis at Clinical
      Hospital of the University of Sao Paulo Medical School, SP.
AB  - Cyclospora cayetanensis causes watery diarrhea in tropical countries, among
      travelers and after ingestion of contaminated water and food. Very little is
      known about its epidemiology, pathogenic aspects and reservoirs. In Brazil, its
      prevalence is unknown and to date there have been reports of three outbreaks. We
      report here a retrospective study of 5,015 stool samples from 4,869 patients
      attended at Clinical Hospital of the University of Sao Paulo Medical School, SP,
      Brazil between April 1996 and January 2002, with 14 cases of Cyclospora
      cayetanensis being detected there was a prevalence of 0.3%. Of the 14 infected
      patients, the mean age was 38 years and 71.4% were female. Ten patients presented
      symptoms; six presented levels of immunological markers and five patients were
      immunodeficient.

PMID- 16082481
TI  - [Loxosceles Heinecken & Lowe, 1835 (Araneae; Sicariidae) species distribution in
      the State of Parana].
AB  - The State of Parana registers on average 2,577 loxoscelic accidents annually. For
      the elaboration of control and management programs one should first determine the
      distribution of the species of the genus Loxosceles. A mapping was performed of
      Loxosceles references in various scientific collections. A total of 1,561 spiders
      were found, identified as Loxosceles intermedia (67%), Loxosceles gaucho (19.5%),
      Loxosceles laeta (10.8%) and Loxosceles hirsuta (2.4%), originating from 20
      regional and 69 municipal health districts. Loxosceles intermedia was present in
      all areas of the state (50 municipal districts), while Loxosceles gaucho occurred
      in the north and northwest, (17 municipal districts), Loxosceles laeta in the
      south (13 municipal districts) and Loxosceles hirsuta in the west and central
      areas (10 municipal districts). Parana has four of the eight species of
      Loxosceles registered in Brazil. Given the medical importance of accidents caused
      by these spiders, it is necessary to perform studies on the location of such
      incidents and investigate areas that have not yet been sampled.

PMID- 16082482
TI  - Preliminary study into the landing behaviour on the human body of morning-biting
      mosquitoes in Atlantic forest in the State of Santa Catarina (Diptera:
      Culicidae).
AB  - Mosquitoes (22 species) (0.5%) and Runchomyia reversa (5%) biting humans in the
      morning in Florianopolis, State of Santa Catarina, were significantly more common
      below than above waist and all Wyeomyia incaudata were collected below the waist.
      Short trousers are not recommended, unless using repellents.

PMID- 16082483
TI  - [Broadening the scope of triatomine research in the attendance of notifications
      of Triatoma sordida (Stal, 1859) in the State of Sao Paulo].
AB  - The objective of this study was to broaden the inspection of home units to a
      radius of 200 meters from the residence of each notified case. The notifications
      received by the regional Services of SUCEN of Sao Jose do Rio Preto, Aracatuba
      and Presidente Prudente were evaluated in August, September and October of 2002.
      There was a total of 263 notifications of triatomines, of which 79 were positive.
      Broadening the scope meant another 610 domestic units were included in the
      investigation and in 14.5% of these triatomines were found. It was observed that
      24.7% of the domestic units neighboring the house of the notified case presented
      positive results in the triatomines investigation. When a notified domestic unit
      presented a positive result, broadening the scope showed positivity in 42.5% of
      neighboring domestic units (Odds ratio 2.252 (1.25<OR<4.06, with a 95% confidence
      limit). This study demonstrated that it is necessary to broaden the scope of
      investigation when attending notifications by the local population.

PMID- 16082484
TI  - [Ethics and medical research: principles, guidelines, and regulations].
AB  - The issue of ethics in medical research grew in importance at the end of World
      War II, after the Nuremberg Code. In this period, some cases in the United States
      had demonstrated the need for the establishment of rules and procedures in
      medical research. In this article, the authors discuss some ethical concepts and
      their philosophical basis, stressing aspects related to research. Ethics in
      medical research is based upon three items: peer approaches, subject informed
      consent, and confidentiality of individual obtained data. The authors also
      summarize the Brazilian laws and directives to follow the precepts and to control
      the process of ethical issues in research with human participants. Finally, they
      approach practical questions of the Informed Consent Form as a consequence of
      their experiences analyzing more than one thousand research projects per year as
      members of the Internal Review Board of the University of Sao Paulo School of
      Medicine, Sao Paulo, Brazil.

PMID- 16082485
TI  - Case report of subcutaneous entomophthoromycosis with retroperitoneal invasion.
AB  - The authors describe a case of entomophthoromycosis in a previously healthy
      patient, who presented with an abscess in the right buttock. After surgical
      drainage it evolved into a retroperitoneal tumor. The patient improved clinically
      after resection of the mass and ketoconazole treatment. The histopathological
      analysis showed the Splendore-Hoeppli phenomenon, suggesting Basidiobolus ranarum
      infection, a zygomycosis generally restricted to the subcutaneous tissue, with
      rare gastrointestinal involvement.

PMID- 16082486
TI  - [Endocervical schistosomiasis].
AB  - We report the case of an asymptomatic 38-year-old woman that sought medical
      assistance due to infertility. The gynecological examination showed an
      endocervical polyp measuring 1.0 x 0.8 x 0.5 cm. A biopsy was performed. Under
      microscopy, several granulomas containing eggs of Schistosoma mansoni were seen.

PMID- 16082487
TI  - Phlebotomine sandflies in a focus of dermal leishmaniasis in the eastern region
      of the Brazilian State of Santa Catarina: preliminary results (Diptera:
      Psychodidae).
AB  - Due to the occurrence of cases of dermal leishmaniasis in the Municipality of
      Picarras, in the East of the Brazilian State of Santa Catarina, collections of
      Phlebotomine sandflies by the use of CDC-like light traps were developed near the
      houses of the patients. Three species (Lutzomyia neivai, Lu. fischeri and Lu.
      ayrozai) were collected. Lu. neivai was predominant near the houses, and Lu.
      ayrozai was collected in a secondary forest in a nearby municipality
      (Navegantes). The novelty of this focus, the most southern one in the East of
      Brazil, underscores the need for more complete studies on the sandfly fauna.

PMID- 16082488
TI  - [Blastocystosis: a high prevalence of cases found in patients from Health Center
      of Soledad, Anzoategui State, Venezuela].
AB  - The parasitological examination of fecal samples from 98 patients from an
      Ambulatory Health Center of Soledad, Anzoategui, Venezuela revealed a rather high
      proportion of results positive for Blastocystis hominis (46.9%).

PMID- 16082489
TI  - An estimation of the frequency of gestational toxoplasmosis in the Brazilian
      Federal District.
AB  - Acute infections by the protozoan Toxoplasma gondii during pregnancy (gestational
      toxoplasmosis) are known to cause serious health problems to the fetus
      (congenital toxoplasmosis). In Brasilia, there have been few studies on the
      incidence of toxoplasmosis. This report summarizes a retrospective study
      performed on 2,636 selected pregnant women attended by the public health system
      of Guara, a satellite-city of Brasilia. In this survey, 17 cases of gestational
      toxoplasmosis were detected; 15 of which were primary maternal infection and the
      remaining 2 were consistent with secondary maternal infection. These results
      suggest an annual seroconversion rate of 0.64 percent (90 percent confidence
      interval: 0.38, 0.90).

PMID- 16082490
TI  - [Is visceral leishmaniasis an endemic disease in Recife, Pernambuco?].

PMID- 16082491
TI  - [Melioidosis in a little rural community of Ceara State].

PMID- 16082492
TI  - [Considerations about global policy for leprosy control].

PMID- 16082494
TI  - Severe gastrointestinal strongyloidiasis.

PMID- 16082495
TI  - 6-[F-18]fluoro-L-DOPA positron emission tomography in the imaging of Merkel cell
      carcinoma: preliminary report of three cases with 2-deoxy-2-[F-18]fluoro-D
      glucose positron emission tomography or pentetreotide-(111In) SPECT data.
AB  - PURPOSE: Merkel cell carcinoma (MCC) is an uncommon and aggressive cutaneous
      neoplasm of neuroendocrine origin. Somatostatin receptor scintigraphy (SRS) and
      positron emission tomography (PET) using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)
      have been proposed to stage MCC and to detect early recurrences. As 6-[F
      18]fluoro-L-DOPA (FDOPA) is taken up by other neuroendocrine tumors, we
      speculated that FDOPA-PET could image MCC. PROCEDURE: FDOPA-PET was performed
      together with FDG-PET (three patients) and SRS (two patients) in different
      clinical settings: localization of the primary tumor, staging, and suspicion of
      recurrence. RESULTS: Uptake of FDOPA-(18F) by MCC was observed in the two true
      positive cases, with an agreement between the results of FDOPA-PET, FDG-PET, and
      SRS; however, the contrast was lower on FDOPA-PET than on FDG-PET images. In the
      last patient suspected of recurrence repeatedly on SRS and with inconclusive FDG
      PET, FDOPA-PET was negative, and a 12-month follow-up demonstrated a true
      negative result. CONCLUSION: MCC takes up FDOPA-(18F). The potential role of
      FDOPA-PET in its management warrants clarification.

PMID- 16082496
TI  - Femoral neck geometry and hip fracture risk: the Geelong osteoporosis study.
AB  - To determine the relationship between femoral neck geometry and the risk of hip
      fracture in post-menopausal Caucasian women, we conducted a retrospective study
      comparing the femoral neck dimensions of 62 hip fracture cases to those of 608
      randomly selected controls. Measurements were made from dual-energy X-ray
      absorptiometry scans (Lunar DPX-L), using the manufacturer's ruler function, and
      included: hip axis length (HAL), femoral neck axis length (FNAL), femoral neck
      width (FNW), femoral shaft width (FSW), medial femoral shaft cortical thickness
      (FSCT(med)), and lateral femoral shaft cortical thickness (FSCT(lat)). The
      fracture group was older (median age 78.3 years vs 73.8 years), lighter (median
      weight 59.9 kg vs 64.5 kg), and, after adjustment for age, taller (mean height
      158.7+/-0.8 cm vs 156.7+/-0.2 cm) than the controls. Furthermore, bone mineral
      density was lower in this group (0.682+/-0.016 g/cm(2) vs 0.791+/-0.006 g/cm(2)).
      After adjustment for age, bone mineral content (BMC) or height, hip fracture
      patients had greater FNW (up to 6.6%) and FSW (up to 6.3%) than did the controls.
      Each standard deviation increase in FNW and FSW was associated with a 1.7-fold
      (95% CI 1.3-2.3) and a 2.4-fold (95% CI 1.8-3.2) increase in the fracture risk,
      respectively. BMC-adjusted FNAL was greater in the fracture group (+2.1%) than in
      the controls, while the age-adjusted FSCT(med) was reduced (-7.2%). There was a
      trend towards longer HAL (up to 2.1%) after adjustment for age or BMC, and
      thinner age-adjusted FSCT(lat) (-1.7%) in fracture patients that did not reach
      statistical significance. In multivariate analysis, the risk of hip fracture was
      predicted by the combination of age, FNW, FSW, BMC and FSCT(med). HAL was not
      analyzed because of the small number of HAL measurements among fracture cases. We
      conclude that post-menopausal women with hip fractures have wider femoral necks
      and shafts, thinner femoral cortices and longer femoral neck axis lengths than do
      women with no fractures. Alteration in hip geometry is associated with the risk
      of hip fracture.

PMID- 16082497
TI  - Calcium metabolism in the frail elderly.
AB  - Elderly residents of aged care facilities are usually considered at high risk of
      osteoporosis not only due to their age, but also due to nutritional factors, poor
      sunlight exposure and renal insufficiency. This study aimed to describe calcium
      metabolism and related hormones in this high-risk population. A total of 1280
      elderly residents of hostels and nursing homes in the northern Sydney area (aged
      65 years or over) had serum analysis for clinical chemistry including serum 25
      hydroxy vitamin D (25OHD) and parathyroid hormone (PTH). Moderate renal
      impairment (creatinine clearance 30-60 ml/min) was common (62%), but
      hypocalcaemia was uncommon (7.0%). Mild hypoalbuminaemia was common (34% below 40
      g/l, but only 3.2% below 35 g/l); 77.5% of the cohort had low serum 25OHD levels
      (<39 nmol/l) and 41.7% had elevated PTH levels (>66 pg/ml). Independent
      predictors of low serum 25OHD levels included gender, age, serum PTH, season,
      mobility and creatinine clearance. Use of vitamin D supplementation conferred
      modestly higher serum 25OHD levels (45.5 vs 27.1 nmol/l in non-supplemented
      residents, p < 0.0001) and lower PTH levels (50.0 vs 78.1 pg/ml, p < 0.0001).
      Despite adequate overall nutrition, vitamin D deficiency is present in the
      majority of this population. Vitamin D deficiency remains a significant public
      health problem in the institutionalized frail elderly. Currently available
      supplements are not adequate or utilized frequently enough to address this
      problem.

PMID- 16082498
TI  - Effects of the piezo-tolerance of cultured deep-sea eel cells on survival rates,
      cell proliferation, and cytoskeletal structures.
AB  - We investigated the pressure tolerance of deep-sea eel (Simenchelys parasiticus;
      habitat depth, 366-2,630 m) cells, conger eel (Conger myriaster) cells, and mouse
      3T3-L1 cells. Although there were no living mouse 3T3-L1 and conger eel cells
      after 130 MPa (0.1 MPa = 1 bar) hydrostatic pressurization for 20 min, all deep
      sea eel cells remained alive after being subjected to pressures up to 150 MPa for
      20 min. Pressurization at 40 MPa for 20 min induced disruption of actin and
      tubulin filaments with profound cell-shape changes in the mouse and conger eel
      cells. In the deep-sea eel cells, microtubules and some actin filaments were
      disrupted after being subjected to hydrostatic pressure of 100 MPa and greater
      for 20 min. Conger eel cells were sensitive to pressure and did not grow at 10
      MPa. Mouse 3T3-L1 cells grew faster under pressure of 5 MPa than at atmospheric
      pressure and stopped growing at 18 MPa. Deep-sea eel cells were capable of growth
      in pressures up to 25 MPa and stopped growing at 30 MPa. Deep-sea eel cells
      required 4 h at 20 MPa to finish the M phase, which was approximately fourfold
      the time required under atmospheric conditions.

PMID- 16082499
TI  - Incisional intercostal hernia after a nephrectomy.
AB  - The aim of the present case report is to present the diagnostic and therapeutic
      challenge of intercostal incisional hernia. We report on a female patient with
      leftsided intercostal incisional hernia between the eleventh and twelfth rib due
      to preceding lumbar incision for tumor nephrectomy. Because of its infrequence,
      diagnosis was established late although simple clinical examination and
      ultrasound investigation displayed the hernia. At laparotomy, a 5x5 cm(2) fascial
      defect with a colonic sliding hernia was found. Hernia repair using permanent
      mesh reinforcement in the retromuscular position is described. Abdominal
      incisional hernia in the intercostal region is rare and therefore easily
      overlooked. As with other incisional hernias, the hernia repair using mesh
      implantation in the retromuscular region is technically feasible and represents
      the treatment of choice.

PMID- 16082500
TI  - What happens to the rectus abdominus fascia after laparoscopic ventral hernia
      repair?
AB  - BACKGROUND: One criticism of laparoscopic ventral hernia repair (LVH) is that the
      rectus muscles are not re-approximated to the midline, and the effect of LVH
      repair on the fascial edges is unclear. Progressive migration of the fascial
      edges toward the midline has been observed anecdotally, but objective evidence
      remains limited. The purpose of this study is to observe the effect of LVH repair
      on the rectus abdominus fascia. METHODS: Patients undergoing LVH repair with
      defects > 10 cm in horizontal diameter were identified prospectively and
      enrolled. All were repaired laparoscopically with intraperitoneal placement of
      mesh (DualMesh, W.L. Gore and Associates) using a standard approach. Radio-opaque
      clips were placed at the fascial edges intraoperatively to mark the defect, and
      plain abdominal films were taken postoperatively (Time 1) to establish the
      initial distance between clips (measured in cm). A subsequent follow-up film was
      taken (Time 2), and the difference in clip distance per patient was recorded.
      Results were analyzed using a chi-squared test. RESULTS: Twelve patients
      qualified for analysis and their results were compared. Mean fascial defect size
      was 15.1 cm (range 8.3-22.0). With respect to change in clip distance from Times
      1 to 2, three events were observed: (1) Diminished (i.e. medialized), (2)
      Enlarged, or (3) No Change. Ten patients (83%) medialized, one patient enlarged,
      and one patient showed no change (chi2 (d.f. = 2) 9.17, p < 0.0023). CONCLUSIONS:
      Medialization of the rectus abdominus fascia occurs in the majority of patients
      undergoing LVH repair. Causes for this phenomenon are unclear: however
      eliminating intrabdominal pressure with intraperitoneal mesh placement likely
      plays a role.

PMID- 16082501
TI  - Almost all about citrulline in mammals.
AB  - Citrulline (Cit, C6H13N3O3), which is a ubiquitous amino acid in mammals, is
      strongly related to arginine. Citrulline metabolism in mammals is divided into
      two fields: free citrulline and citrullinated proteins. Free citrulline
      metabolism involves three key enzymes: NO synthase (NOS) and ornithine
      carbamoyltransferase (OCT) which produce citrulline, and argininosuccinate
      synthetase (ASS) that converts it into argininosuccinate. The tissue distribution
      of these enzymes distinguishes three "orthogonal" metabolic pathways for
      citrulline. Firstly, in the liver, citrulline is locally synthesized by OCT and
      metabolized by ASS for urea production. Secondly, in most of the tissues
      producing NO, citrulline is recycled into arginine via ASS to increase arginine
      availability for NO production. Thirdly, citrulline is synthesized in the gut
      from glutamine (with OCT), released into the blood and converted back into
      arginine in the kidneys (by ASS); in this pathway, circulating citrulline is in
      fact a masked form of arginine to avoid liver captation. Each of these pathways
      has related pathologies and, even more interestingly, citrulline could
      potentially be used to monitor or treat some of these pathologies. Citrulline has
      long been administered in the treatment of inherited urea cycle disorders, and
      recent studies suggest that citrulline may be used to control the production of
      NO. Recently, citrulline was demonstrated as a potentially useful marker of short
      bowel function in a wide range of pathologies. One of the most promising research
      directions deals with the administration of citrulline as a more efficient
      alternative to arginine, especially against underlying splanchnic sequestration
      of amino acids. Protein citrullination results from post-translational
      modification of arginine; that occurs mainly in keratinization-related proteins
      and myelins, and insufficiencies in this citrullination occur in some auto-immune
      diseases such as rheumatoid arthritis, psoriasis or multiple sclerosis.

PMID- 16082502
TI  - Teratogenicity of 3-hydroxynorvaline in chicken and mouse embryos.
AB  - 3-Hydroxynorvaline (HNV; 2-amino-3-hydroxypentanoic acid), a microbial L
      threonine analogue, is toxic to mammalian cells and displays antiviral
      properties. In view of this, we investigated the toxicity and/or potential
      teratogenicity of HNV in developing chicken and mouse embryos. HNV was
      administered to chicken embryos (in ovo; dose 75-300 mumole/egg; 48 h post
      incubation) and pregnant Hanover NMRI mice (per os; total dose 900-1800 mg/kg
      body mass; gestation days 7-9). Control animals received sterile saline
      solutions. Harvested embryos (chicken embryos, 10 days post-incubation; mouse
      embryos; gestation day 18) were fixed in glutaraldehyde and stereomicroscopically
      inspected for signs of dysmorphogenesis. Body mass, body and toe length and
      mortality of chicken embryos, and the body mass and mortality of mouse embryos
      were recorded. HNV exposure significantly increased the incidence of embryotoxic
      (growth retardation, toxic mortality) and congenital defects in both chicken and
      mouse embryos. All the observed effects were dose-dependent. In conclusion, HNV
      is an embryotoxic and teratogenic compound, which caused significant
      developmental delay and congenital defects in developing chicken and mouse
      embryos.

PMID- 16082503
TI  - Potent isozyme-selective inhibition of human glutathione S-transferase A1-1 by a
      novel glutathione S-conjugate.
AB  - Elevated levels of glutathione S-transferases (GSTs) are among the factors
      associated with an increased resistance of tumors to a variety of antineoplastic
      drugs. Hence a major advancement to overcome GST-mediated detoxification of
      antineoplastic drugs is the development of GST inhibitors. Two such agents have
      been synthesized and tested on the human Alpha, Mu and Pi GST classes, which are
      the most representative targets for inhibitor design. The novel fluorescent
      glutathione S-conjugate L-gamma-glutamyl-(S-9-fluorenylmethyl)-L-cysteinyl
      glycine (4) has been found to be a highly potent inhibitor of human GSTA1-1 in
      vitro (IC50=0.11+/-0.01 microM). The peptide is also able to inhibit GSTP1-1 and
      GSTM2-2 isoenzymes efficiently. The backbone-modified analog L-gamma-(gamma
      oxa)glutamyl-(S-9-fluorenylmethyl)-L-cysteinyl-glycine (6), containing an
      urethanic junction as isosteric replacement of the gamma-glutamyl-cysteine
      peptide bond, has been developed as gamma-glutamyl transpeptidase-resistant mimic
      of 4 and evaluated in the same inhibition tests. The pseudopeptide 6 was shown to
      inhibit the GSTA1-1 protein, albeit to a lesser extent than the lead compound,
      with no effect on the activity of the isoenzymes belonging to the Mu and Pi
      classes. The comparative loss in biological activity consequent to the isosteric
      change confirms that the gamma-glutamyl moiety plays an important role in
      modulating the affinity of the ligands addressed to interact with GSH-dependent
      proteins. The new specific inhibitors may have a potential in counteracting tumor
      protective effects depending upon GSTA1-1 activity.

PMID- 16082504
TI  - Plasma levels of amino acids in elderly long term care residents with
      oropharyngeal dysphagia: comparison of hand-oral with tube-enteral-fed patients.
AB  - BACKGROUND: Dysphagia and eating difficulties are highly prevalent in long term
      care patients. Evaluation of their nutritional status is complicated by
      comorbidity, frailty and individual patterns of feeding. In previous studies we
      found vitamin deficiencies (folic acid B6 and B12) in orally fed elderly in early
      stages of oropharyngeal dysphagia despite satisfactory nutritional parameters
      (BMI, albumin and hemoglobin). The aim of this study is to evaluate the plasma
      amino acids levels in these hand-oral fed elderly patients with dysphagia.
      METHODS: Plasma amino acids were measured in 15 orally fed elderly patients in
      early functional outcome swallowing scale (FOSS), stage 2, and compared with
      those of 15 matched nasogastric-tube-fed counterparts. RESULTS: The plasma levels
      of all measured amino acids, ratio of essential to nonessential, levels of
      conditionally essential and the immune-enhancing amino acids were similar in both
      groups and within the normal range of our laboratory. The traditional nutritional
      parameters were also similar in both groups and within the normal range.
      CONCLUSIONS: Plasma levels of amino acids in elderly patients in early stage of
      FOSS are satisfactory, supporting the view that their protein intake is adequate.
      Further studies should concentrate on patients in advanced stages of FOSS.

PMID- 16082505
TI  - Repeated Catha edulis oral administration enhances the baseline aggressive
      behavior in isolated rats.
AB  - The effects of repeated oral administration of the psychostimulant plant, Catha
      edulis and its active principle, cathinone on rats were studied using isolation
      induced aggression paradigm. The behavioral responses were videotaped and scored
      later by offline data analyses. Rats were decapitated at the end of the
      behavioral experiment and in the relevant brain regions, monoamines were
      assessed. The results demonstrate that isolation of male rats produces a baseline
      aggression. Treatments with the psychostimulant plant, Catha edulis or commercial
      S-(--)-cathinone enhanced significantly: The locomotor activities and the
      baseline aggression behaviors compared with vehicle treated rats. Neurochemical
      correlates revealed a significant depletion of serotonin (5-HT) and its
      corresponding metabolites (5-HIAA) in both the anterior and posterior striatum.
      There was also a reduction in the level of homovanillic acid (HVA) in the
      hippocampus. Additionally, elevation of dopamine level was observed in the
      nucleus accumbens, especially, in those rats treated with Catha edulis extract.
      Cathinone, on the other hand, increased the level of HVA in the posterior
      striatum and decreased HVA in the nucleus accumbens. In conclusion, the present
      data demonstrate that repeated administration of Catha edulis or S-(--)-cathinone
      enhances aggression in rats, presumably by decreasing the level of serotonin and
      its corresponding metabolites. Besides, the data obtained do not rule out the
      involvement of dopamine in aggression behavior.

PMID- 16082506
TI  - Effects of anaesthetics on the loss of nigrostriatal dopaminergic neurons by 6
      hydroxydopamine in rats.
AB  - Various studies use ketamine/xylazine, fentanyl/medetomidine,
      etorphine/methotrimeprazine, and isoflurane anaesthesia for creating the 6
      hydroxydopamine (6-OHDA)-lesion rat model of Parkinson's disease. As these
      anaesthetics are known to modulate uptake and turnover of dopamine and that 6
      OHDA-induced neurotoxicity is also dependents on uptake/turnover, we studied the
      effects of these anaesthetics on the extent of nigrostriatal dopaminergic damage
      caused by 6-OHDA. Infusion of 8 microg of 6-OHDA into the medial forebrain bundle
      significantly reduced the numbers of dopaminergic cells in nigra and striatal
      concentrations of dopamine in animals anaesthetized with fentanyl/medetomidine,
      etorphine/methotrimeprazine and isoflurane but not with ketamine/xylazine. In the
      latter group, however, increasing the dose of 6-OHDA to 10 and 12 microg resulted
      in a moderate (15 and 29%), but significant loss of dopaminergic cells. A severe
      loss of dopaminergic cells (59% and 81%) was seen with these doses in isoflurane
      anaesthetized animals, but with only 8 microg in etorphine/methotrimeprazine
      anaesthetized animals. Thus, these results suggest that the extent of
      nigrostriatal dopaminergic neuronal loss with 6-OHDA seems to be influenced by
      anaesthetic used during the surgery.

PMID- 16082507
TI  - Functional imaging with positron emission tomography in multiple system atrophy.
AB  - Although the current guidelines for the clinical diagnosis of multiple system
      atrophy (MSA) do not require structural or functional brain imaging,
      investigations utilizing positron emission tomography (PET) have been helpful
      diagnostically in differentiating between MSA and primary autonomic failure;
      idiopathic Parkinson's disease; and sporadic olivopontocerebellar atrophy. These
      investigations have demonstrated different patterns of cerebral glucose
      utilization and of nigrostriatal projection abnormalities among these disorders
      and between the cerebellar and parkinsonian forms of MSA. Most of the studies
      have focused upon patients with well-established disease and none have examined
      the utility of PET imaging in early stage patients with follow-up of clinical
      course and autopsy verification to ensure accuracy of diagnosis and to determine
      the sensitivity and specificity of PET techniques for diagnosis. Recent PET
      studies have revealed denervation of myocardial post-ganglionic sympathetic
      neurons in some MSA patients, indicating that this disorder can affect the
      peripheral autonomic as well as the central nervous system. Investigations
      utilizing ligands to quantify central nervous system dopaminergic and cholinergic
      terminals have begun to provide insight into the neurochemical disorders that may
      underlie two of the sleep disturbances common in MSA, rapid eye movement sleep
      behavior disorder and obstructive sleep apnea.

PMID- 16082508
TI  - No association of serotonin transporter gene (SLC6A4) with schizophrenia and
      bipolar disorder in Japanese patients: association analysis based on linkage
      disequilibrium.
AB  - Serotonin transporter gene (SLC6A4) is one of the most promising candidate genes
      for psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BP).
      Two functional polymorphisms, 5HTTLPR and 5HTTVNTR, have been a focus for genetic
      association analyses; however, no conclusive results have been obtained. We
      conducted, 1) a mutation search of SLC6A4, 2) LD mapping to select 'tagging'
      markers (10 SNPs and 5HTTVNTR, while 5HTTLPR was treated as an independent marker
      because of its allelic form), and 3) association analysis of these 'tagging'
      markers and independent markers (5HTTLPR and Asn605Lys) with SCZ and BP in
      Japanese patients. In this mutation search, a nonsynonymous SNP, Asn605Lys, was
      detected. No associations of 'tagging' markers and independent markers with such
      conditions were found. These results indicate that SLC6A4 might not play a major
      role in SCZ and BP in Japanese patients, a finding that agrees with both the
      common disease-common variant hypothesis and common disease-rare variant
      hypothesis.

PMID- 16082509
TI  - Sleep disorders in multiple system atrophy.
AB  - Complaints about sleep disorders and excessive daytime sleepiness are common
      among patients with multiple system atrophy. The diffuse neurodegenerative
      process that encompasses the key structures involved in the regulation of the
      sleep/wake transition and respiratory function may account for these complaints
      and for the most frequent polysomnographic findings in MSA, i.e., sleep-related
      breathing disturbances and REM sleep behaviour disorder, which are both treatable
      conditions. Nocturnal stridor is an inspiratory sound produced by complex vocal
      cord muscle dysfunction. Often occurring with sleep apnoea, stridor is associated
      with decreased survival. REM sleep behaviour disorder, a parasomnia characterized
      by loss of normal skeletal muscle atonia during REM sleep with prominent motor
      activity, is detected in almost all patients. The pathophysiology of both
      disorders is partially elucidated but increasing evidence points to the role of
      basal ganglia dysfunction.

PMID- 16082510
TI  - Poor evidence for depolarization block but uncoupling of nigral from striatal
      dopamine metabolism after chronic haloperidol treatment in the rat.
AB  - Chronic haloperidol treatment induces depolarization block in midbrain dopamine
      neuronal systems. We studied the effect of this treatment on nigrostriatal
      dopamine catabolism using microwave fixation in situ of the brain to prevent post
      mortem changes. Male Sprague-Dawley rats were given haloperidol (0.4 mg/kg/day,
      i.p.) or vehicle for 21 days. On day 22, some rats in each group received a
      haloperidol challenge (0.4 mg/kg, i.p.), and the remaining rats were given the
      vehicle. Dopamine metabolite levels 60 min after the challenge were assayed by
      combined gas chromatography-mass fragmentography. Haloperidol pretreatment
      significantly modified haloperidol challenge effect on regional dopamine
      metabolite contents. The challenge elevated all striatal metabolites studied
      similarly in the chronic vehicle- or chronic haloperidol-pretreated rats. In
      contrast, it did not significantly affect nigral dopamine metabolites except it
      elevated 3,4-dihydroxyphenylacetic acid in the haloperidol-pretreated rats. A
      linear correlation between the nigral and striatal contents of 3-methoxytyramine
      (R = 0.72, p = 0.03), and a trend for correlation (R = 0.65, p = 0.06) between
      the respective 3,4-dihydroxyphenylacetic acid contents were found after the
      haloperidol challenge in the vehicle-pretreated rats only. These results suggest
      that chronic haloperidol treatment uncouples somatodendritic dopamine turnover
      and release from those in the axon terminals of nigrostriatal dopamine neurons.

PMID- 16082511
TI  - Kinematic analysis of dopaminergic effects on skilled handwriting movements in
      Parkinson's disease.
AB  - Patients with Parkinson's disease (PD) exhibit impairments in the execution of
      highly practiced and skilled motor actions such as handwriting. The analysis of
      kinematic aspects of handwriting movements has demonstrated that size, speed,
      acceleration and stroke duration are affected in PD. Although beneficial effects
      of dopaminergic therapy in regard to execution of movements have been reported,
      the effects of pharmacological therapy on these measures have not been examined
      in detail. The present study has compared kinematic aspects of handwriting
      movements of 27 healthy subjects and 27 patients with PD both on their usual
      dopaminergic treatment and following withdrawal of dopaminergic medication.
      Healthy subjects were matched with PD patients according to age, sex, handedness
      and education level. A digitising tablet was used for the assessment of
      handwriting movements. Subjects were asked to perform a simple writing task.
      Movement time, distance, velocity, acceleration and measures of fluency of
      handwriting movements were measured. Compared with healthy subjects, the
      kinematics of handwriting movements in PD patients were markedly disturbed
      following withdrawal of dopaminergic medication. Although dopaminergic treatment
      in PD patients resulted in marked improvements in the kinematics of handwriting
      movements, PD patients did not reach an undisturbed level of performance. The
      results suggest that dopamine medication results in partial restoration of
      automatic movement execution.

PMID- 16082512
TI  - Children with oppositional-defiant disorder display deviant attentional
      processing independent of ADHD symptoms.
AB  - OBJECTIVE: To examine neurophysiological correlates of attentional processing in
      children with oppositional-defiant disorder (ODD) independent of ADHD symptoms.
      METHOD: Thirteen children with oppositional-defiant disorder without comorbid
      ADHD symptoms and 13 healthy control children (all 11 years) performed a cued
      Continuous Performance Test (CPT-AX). Event-related potentials (ERP) to cue and
      target stimuli were examined for group differences. RESULTS: Children with ODD
      showed significantly reduced parietal P3a and P3b amplitudes to cues and to
      targets, compared with healthy controls. ERP amplitudes correlated with
      oppositional and aggressive behavior scores. CONCLUSIONS: Event-related
      potentials revealed reduced orienting to cues and reduced executive target
      processing in children with ODD. These findings indicate that ODD children show
      neurophysiological deviances independent of ADHD comorbidity.

PMID- 16082513
TI  - Oculomotor inhibition in children with and without attention-deficit
      hyperactivity disorder (ADHD).
AB  - The aim of the present study was to distinguish between a general deficit in
      oculomotor control and a deficit restricted to inhibitory functions in children
      with attention deficit hyperactivity disorder (ADHD). In addition, we were
      interested in differentiating between a general inhibition deficit and deficient
      subfunctions of inhibition. We used a prosaccade task to measure general
      oculomotor abilities in 22 children with ADHD and in age- and gender-matched
      healthy controls. A fixation, an antisaccade and a countermanding saccade task
      were used to measure specific aspects of oculomotor inhibition. Two major results
      were obtained: First, our prosaccade task suggests similar saccadic response
      preparation and saccadic accuracy in the ADHD compared to the control children.
      Secondly, the fixation and the countermanding saccade task indicate deficits on
      measures of oculomotor inhibition in the ADHD group. While patients were
      specifically impaired in stopping an already initiated response or in suppressing
      exploratory saccades in a novel situation, inhibition of a prepotent response was
      not deficient. Our data thus indicate an underlying impairment in cognitive
      inhibition in ADHD that has been associated with prefrontal lobe functions. More
      specifically, as the anterior cingulate gyrus has been associated with the
      countermanding saccade task and group differences were most pronounced in this
      paradigm our data are in line with imaging data stressing the importance of this
      cortical structure in the pathophysiology of ADHD.

PMID- 16082514
TI  - Subchronic treatment with kynurenine and probenecid: effects on prepulse
      inhibition and firing of midbrain dopamine neurons.
AB  - Acute elevation of the endogenous NMDA-receptor antagonist kynurenic acid (KYNA)
      is associated with an increased neuronal activity of rat ventral tegmental area
      (VTA) dopamine (DA) neurons and disruption in prepulse inhibition (PPI). In the
      present study, the effects of subchronic exposure to kynurenine and probenecid
      (20 mg/kg/day and 10 mg/kg/day, respectively for 14 days), aiming at increasing
      brain KYNA turnover, on rat VTA dopaminergic firing and on PPI were investigated.
      This treatment increased neuronal firing of VTA DA neurons, changed the response
      of these neurons to systemically administered nicotine (3-400 microg/kg, i.v.)
      and tended to disrupt PPI. Present results show that the effect on firing of VTA
      DA neurons by acutely elevated levels of brain KYNA also persists following
      subchronic exposure. In addition, no adaptive changes seem to occur with regard
      to the electrophysiological effects of KYNA on VTA DA neurons following
      subchronic treatment with kynurenine and probenecid.

PMID- 16082515
TI  - Postnatal iron-induced motor behaviour alterations following chronic neuroleptic
      administration in mice.
AB  - C57/BL6 mice were administered either 7.5 mg Fe(2+)/kg or vehicle (saline)
      postnatally on days 10-12 after birth. From 61 days of age onwards for 21 days,
      groups of mice were administered either clozapine (1 or 5 mg/kg, s.c.) or
      haloperidol (1 mg/kg, s.c.) or vehicle (Tween-80). Twenty-four hours after the
      final injection of either neuroleptic compound or vehicle, spontaneous motor
      activity was measured over a 60-min interval. Following this, each animal was
      removed, injected apomorphine (1 mg/kg, s.c.) and replaced in the same test
      chamber. It was found that postnatal administration of Fe(2+) at the 7.5 mg/kg
      dose level reduced activity during the initial 20-min periods (0-20 and 20-40
      min) and then induced hyperactivity during the final 20-min period over all three
      parameters of activity. Subchronic treatment with the higher, 5 mg/kg, dose of
      clozapine abolished or attenuated the hypoactivity in by postnatal Fe(2+) during
      the 1(st) two 20-min periods over all three parameters of activity. Subchronic
      treatment with the higher, 5 mg/kg, dose of clozapine abolished or attenuated the
      hyperactivity in by postnatal Fe(2+) during the 3(rd) and final 20-min period.
      Subchronic administration of haloperidol, without postnatal iron, increased the
      level of both locomotion (1(st) 20 min) and rearing (2(nd) 20 min) activity.
      Postnatal administration of Fe(2+) at the 7.5 mg/kg dose increased the levels of
      both locomotion and rearing, but not total activity, following administration of
      apomorphine (1 mg/kg). Subchronic administration of clozapine, at both the 1 and
      5 mg/kg doses, reduced the increased locomotor activity caused by postnatal
      Fe(2+), whereas clozapine, 5 mg/kg, elevated further the postnatal Fe(2+)-induced
      increased in rearing. Subchronic administration of clozapine, at both the 1 and 5
      mg/kg doses, and haloperidol, 1 mg/kg, increased the level of locomotor following
      administration of apomorphine (1 mg/kg) in mice treated postnatally with vehicle,
      whereas only clozapine increased the level of rearing. Correlational analyses
      indicated that both apomorphine-induced locomotion and rearing were highly
      correlated with the total iron content in the basal ganglia, thereby offering
      direct evidence of the linear relationship between iron content in the basal
      ganglia and the behavioural expression of DA D(2)-receptor supersensitivity in
      mice.

PMID- 16082516
TI  - The impact of subsidized health insurance for the poor: evaluating the Colombian
      experience using propensity score matching.
AB  - This paper evaluates the impact of Colombia's subsidized health insurance program
      (SUBS) on medical care utilization. Colombia's SUBS program is a demand-side
      subsidy intended for low-income families, where the screening of beneficiaries
      takes place in decentralized locations across the country. Due to the self
      selection problems associated with non-experimental data, we implement Propensity
      Score Matching (PSM) methods to measure the impact of this subsidy on medical
      care utilization. By combining unique household survey data with community and
      regional data, we are able to compute propensity scores in a way that is
      consistent with both the local government's decision to offer the subsidy, and
      with the individual's decision to accept the subsidy. Although the application of
      PSM using these rich datasets helps to achieve a balance between the treatment
      and control groups along observable dimensions, we also present instrumental
      variable estimates to control for the potential endogeneity of program
      participation. Using both methods, we find that Colombia's subsidized insurance
      program greatly increased medical care utilization among the country's poor and
      uninsured. This evidence supports the case for other Latin American countries
      implementing similar subsidy programs for health insurance for the poor.

PMID- 16082517
TI  - Innovations in health care financing: new evidence on the prospect of community
      health insurance schemes in the rural areas of Ethiopia.
AB  - It has become clear that due to market failure, state failure, and other reasons,
      the conventional sources of finance alone could not solve the health problem of
      the rural population, particularly that of the socially excluded and
      disadvantaged groups. Community Based Health Insurance Schemes (CBHIS) are one of
      the most recently mentioned options to narrow the existing inequalities in access
      to basic health services. This study assesses the prospect of CBHIS in the rural
      areas of Ethiopia using a double bounded dichotomous contingent valuation method.
      The results show that even in one of the poorest countries of the world, there is
      a promising prospect to introduce CBHIS.

PMID- 16082518
TI  - Medicaid coverage and medical interventions during pregnancy.
AB  - This paper extends prior research on the effect of Medicaid coverage on medical
      interventions during pregnancy (prenatal ultrasound) and birth (ultrasound during
      delivery, cesarean delivery, inducement, and fetal monitor). The data are from
      two sources: the New York State Vital Statistics (VS) matched infant birth-death
      file and the Statewide Planning and Research Cooperative System (SPARCS) file for
      1993--1996. Medicaid coverage increases the likelihood of teens and adults
      receiving prenatal care relative to being uninsured. Overall, the effect of
      insurance type varies depending on whether the procedure is part of standard care
      (ultrasound and fetal monitor) or more likely to be elective (inducement and
      cesarean delivery). Insurance type has a greater effect for elective procedures
      than for procedures that are part of standard care.

PMID- 16082519
TI  - The impact of asymmetric information and ownership on nursing home access.
AB  - A consistent pattern in the nursing home industry is that non-profit institutions
      serve a lower proportion of Medicaid patients than do for-profit facilities. This
      is contrary to the expectation that non-profit, altruistically motivated firms
      should serve a larger proportion of the less profitable Medicaid patients than
      proprietary firms. The literature confirms this pattern empirically, but provides
      no theoretical basis for it, which is the contribution of this paper.
      Specifically, we show theoretically that information disparities between
      providers and consumers regarding quality fosters an environment in which the
      percentage of uninformed consumers is a key factor in determining public-private
      patient mix.

PMID- 16082520
TI  - Expression patterns of nm23 genes during mouse organogenesis.
AB  - Nucleoside di-phosphate kinase enzyme (NDPK) isoforms, encoded by the nm23 family
      of genes, may be involved in various cellular differentiation and proliferation
      processes. We have therefore analyzed the expression of nm23-M1, -M2, -M3, and 
      M4 during embryonic mouse development. In situ hybridization data has revealed
      the differential expression of nm23 mRNA during organogenesis. Whereas nm23-M1
      and -M3 are preferentially expressed in the nervous and sensory systems, nm23-M2
      mRNA is found ubiquitously. Irrespective of the developmental state studied, nm23
      M4 mRNA is only expressed at low levels in a few embryonic organs. In the
      cerebellum and cerebral cortex, nm23-M1, -M2, and -M3 are present in the neuronal
      differentiation layer, whereas nm23-M4 mRNA is distributed in the proliferating
      layer. Thus, nm23 mRNA is differentially expressed, and the diverse NDPK isoforms
      are sequentially involved in various developmental processes.

PMID- 16082521
TI  - A neural network to improve dim-light vision? Dendritic fields of first-order
      interneurons in the nocturnal bee Megalopta genalis.
AB  - Using the combined Golgi-electron microscopy technique, we have determined the
      three-dimensional dendritic fields of the short visual fibres (svf 1-3) and first
      order interneurons or L-fibres (L1-4) within the first optic ganglion (lamina) of
      the nocturnal bee Megalopta genalis. Serial cross sections have revealed that the
      svf type 2 branches into one adjacent neural unit (cartridge) in layer A, the
      most distal of the three lamina layers A, B and C. All L-fibres, except L1-a,
      exhibit wide lateral branching into several neighbouring cartridges. L1-b shows a
      dendritic field of seven cartridges in layers A and C, dendrites of L2 target 13
      cartridges in layer A, L3 branches over a total of 12 cartridges in layer A and
      three in layer C and L4 has the largest dendritic field size of 18 cartridges in
      layer C. The number of cartridges reached by the respective L-fibres is
      distinctly greater in the nocturnal bee than in the worker honeybee and is larger
      than could be estimated from our previous Golgi-light microscopy study. The
      extreme dorso-ventrally oriented dendritic field of L4 in M. genalis may, in
      addition to its potential role in spatial summation, be involved in edge
      detection. Thus, we have shown that the amount of lateral spreading present in
      the lamina provides the anatomical basis for the required spatial summation.
      Theoretical and future physiological work should further elucidate the roles that
      this lateral spreading plays to improve dim-light vision in nocturnal insects.

PMID- 16082522
TI  - Molecular characterization of soluble factors from human menstrual effluent that
      induce epithelial to mesenchymal transitions in mesothelial cells.
AB  - We have studied menstrual effluent in order to identify soluble menstrual factors
      that induce epithelial to mesenchymal transitions (EMT) in mesothelial cells. A
      variety of molecules, such as nitric oxide and its reaction products, proteases
      (i.e. matrix metalloproteinases, plasmin) and proteins and/or peptides (i.e.
      growth factors: b-fibroblast growth factor, epidermal growth factor, hepatocyte
      growth factor, transforming growth factor-beta; cytokines: interleukin 1 beta,
      tumour necrosis factor-alpha [TNF-alpha]) may be involved in this process. We
      have demonstrated that TNF-alpha is involved in EMT, whereas the other molecules
      are not. Biochemical analysis has shown that the inducing menstrual factors are
      heat-labile molecules, are uncharged at neutral pH, have a molecular weight
      between 50-70 kDa (or are bound in complexes of that size) and are eluted in the
      albumin fraction during gel filtration chromatography. Further analysis of this
      fraction by using proteomics and mass spectrometry has led to the identification
      of alpha-enolase and haemoglobin whose inhibition partially prevents EMT. When
      antibodies against TNF-alpha, alpha-enolase and haemoglobin are combined, EMT is
      almost completely inhibited. Thus, the candidates for soluble menstrual factors
      that induce mesothelial EMT are TNF-alpha, alpha-enolase and haemoglobin.

PMID- 16082523
TI  - Expression of asexual developmental regulator gene abaA is affected in the double
      mutants of classes I and II chitin synthase genes, chsC and chsA, of Aspergillus
      nidulans.
AB  - The chsA and chsC encode classes II and I chitin synthases, respectively, of the
      filamentous fungus Aspergillus nidulans. The DeltachsA DeltachsC double mutants
      (DeltaAC mutants) show defects in asexual development: a striking reduction in
      the number of conidiophores and aberrant conidiophore morphology. Here, we
      examined the involvement of regulatory genes for asexual development (brlA, abaA,
      and medA) in the conidiation defects of the DeltaAC mutants. Spatial expression
      patterns of brlA, abaA, and medA in conidiophores of the wild-type strains and
      DeltaAC mutants were examined by in-situ staining using a reporter gene;
      expression of either gene was detected at abnormal sterigmata in the DeltaAC
      mutants as well as at normal ones in the wild-type strain. However, abaA
      expression was not prominent at a subset of conidiophores developing long chains
      of aberrant sterigmata, suggesting that induction of the abaA expression was
      retarded in the DeltaAC mutants. Based on these results and those previously
      presented, possible mechanisms involved in the conidiation defects are discussed.

PMID- 16082525
TI  - [Avoiding emergency situations under anticoagulant therapy with vitamin K
      antagonists].
AB  - Despite 50 years of clinical experience with vitamin K antagonists such as
      phenprocoumon or warfarin, many clinicians are uncertain how to start treatment,
      deal with overdose or bleeding complications, and how to bridge anticoagulation
      when treatment with vitamin K antagonists is interrupted. Patients with overdose
      of vitamin K antagonists or bleeding complications are treated with vitamin K,
      prothrombin complex concentrates (PCC), or recombinant factor VIIa. Rapid
      reversal of anticoagulation is only achieved by using PCC or recombinant factor
      VIIa. Both should be combined with vitamin K for a sustained effect. For elective
      surgery, treatment with vitamin K antagonists is paused and vitamin K given
      either orally or intravenously. Unfractionated or low molecular weight heparin is
      given when INR levels are below therapeutic range. Patients with
      contraindications to heparin may be treated with alternative anticoagulants such
      as danaparoid, lepirudin or fondaparinux.

PMID- 16082526
TI  - [Clinical gait analysis].
AB  - Clinical gait analysis comprises a well defined repertoire of various methods for
      valid and reliable assessment. The rapid development of corresponding hardware
      and software has substantially decreased the efforts necessary for data
      processing and has promoted the clinical applicability of the procedures. The
      clinical question defines the amount of methodological input. Clinical gait
      analysis may provide diagnostic insight into the pathobiomechanics and the
      pathophysiology of complex gait disorders for which a profound understanding of
      the underlying causes is a prerequisite for adequate treatment. The methods may
      help in the screening of gait function following reconstructive surgery as a
      measure of quality control, the assessment of the severity of a gait disturbance,
      the evaluation of a rehabilitation process, or the quantification of the effect
      of orthoses, insoles or specific shoe ware. Simple procedures of gait analysis
      may suffice to obtain information on gait function which can not be derived by
      mere clinical observation and which can be incorporated into a clinical concept.

PMID- 16082527
TI  - [Cognitive impairment, depression, and work capacity of 50-59-year-old
      psychosomatic inpatients].
AB  - Due to aging of the population and a possible rise in retirement age, the
      cognitive capacity of older people is gaining great importance. As evidenced by
      the increase in early retirement due to psychosomatic disease, many employees are
      not capable of working at a higher age. Decreasing cognitive abilities have
      usually been studied in subjects over 65 years based on the heterogeneous
      construct of mild cognitive impairment (MCI). This study investigates the
      prevalence of cognitive impairments in the age group from 50 to 59 years and
      their reflections in subjective vocational achievement and social medical
      evaluation. Having been assigned to inpatient rehabilitation due to decreasing
      work performance, these patients could be considered a risk group for developing
      MCI. A battery of standardized cognitive tests was conducted with patients at a
      psychosomatic hospital (Termine Test, CVLT, Block Design, TAP, and Tower of
      Hanoi). The MCI was defined by performance below the average age norm in at least
      two of five functional areas. Depression was assessed by the Beck Depression
      Inventory. Cognitive impairment was observed in 24% of participants. These
      patients also described vocational difficulties. Cognitive impairments of older
      employees could possibly be compensated for by specific training programs in
      order to maintain or rebuild their work capacity.

PMID- 16082528
TI  - Adverse effects of left ventricular hypertrophy in the reduction of endpoints in
      NIDDM with the angiotensin II antagonist losartan (RENAAL) study.
AB  - AIMS/HYPOTHESIS: We explored the impact of baseline left ventricular hypertrophy
      (LVH) and losartan treatment on renal and cardiovascular (CV) events in 1,513
      patients from the Reduction of Endpoints in NIDDM with the Angiotensin II
      Antagonist Losartan (RENAAL) trial, which studied the effects of losartan on the
      progression of renal disease and/or death in patients with type 2 diabetes and
      nephropathy. MATERIALS AND METHODS: LVH was assessed using ECG criteria (Cornell
      product and/or Sokolow-Lyon voltage). The risk of renal or CV events was
      determined by a proportional hazards model fit with treatment allocation and
      presence of LVH. Covariates at baseline included age, sex, systolic BP, mean
      arterial pressure, pulse, proteinuria, serum creatinine, albumin and haemoglobin.
      RESULTS: A total of 187 subjects (12%) had LVH at baseline. Treatment with
      losartan resulted in a significant decrease in the Cornell product (-6.2%) and
      Sokolow-Lyon voltage (-6.3%). LVH was shown to be significantly associated with
      the primary endpoint, which was a composite of doubling of serum creatinine
      (DSCR), endstage renal disease (ESRD) or death (hazard ratio [HR]=1.44, p=0.011),
      as well as with the composite renal endpoint of DSCR/ESRD (HR=1.42, p=0.031) and
      CV events (HR=1.68, p=0.001). Losartan treatment of patients with LVH decreased
      the CV as well as renal risk to a level similar to that of patients without LVH.
      CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes and nephropathy, LVH
      is associated with significantly increased risk of CV events and the progression
      of kidney disease. Importantly, in patients with LVH, losartan reduced the CV as
      well as the renal risk to a level similar to that seen in subjects without LVH.

PMID- 16082529
TI  - Association between polymorphisms in the nuclear respiratory factor 1 gene and
      type 2 diabetes mellitus in the Korean population.
AB  - AIMS/HYPOTHESIS: Dysfunction in mitochondrial oxidative phosphorylation plays a
      central role in insulin resistance and type 2 diabetes. Nuclear respiratory
      factor 1 (NRF1) is a transcription factor that acts on nuclear genes encoding
      respiratory subunits and components of the mitochondrial transcription and
      replication machinery. Thus, we investigated its genetic association with type 2
      diabetes. METHODS: The NRF1 gene was sequenced to identify polymorphisms in 24
      Korean DNA samples and then common variants were genotyped in 766 patients with
      type 2 diabetes and 303 non-diabetic subjects. RESULTS: Twelve single nucleotide
      polymorphisms and one insertion/deletion polymorphism were identified. Six common
      variants among them were genotyped in a larger study. Although three individual
      polymorphisms appeared to be associated with type 2 diabetes (g.-46350insdel A,
      g.+141G>T and g.+54529A>G), the effects were only marginal. However, a haplotype
      (H2) was associated with a decreased risk of type 2 diabetes and another
      haplotype (H4) was associated with an increased risk of type 2 diabetes (p values
      for the Haplo. Score test were 0.009 and 0.004, respectively).
      CONCLUSIONS/INTERPRETATION: We demonstrated that two common haplotypes of NRF1
      gene are associated with type 2 diabetes in the Korean population.

PMID- 16082530
TI  - Addressing faculty objections to the implementation of active learning strategies
      in the analytical chemistry course.

PMID- 16082531
TI  - Use of solid-phase extraction to enable enhanced detection of acyl homoserine
      lactones (AHLs) in environmental samples.
AB  - A challenge for understanding the role of bacterial cell-cell signalling in the
      environment is the detection of those signals, which are often present in low
      (nmol L(-1)) concentrations. We describe here a simple purification method, solid
      phase extraction (SPE), for increasing the sensitivity of detection for one such
      group of signals, acyl homoserine lactones (AHLs), in environmental samples.
      Spiking of dried marine sponge tissue (Stylinos sp.) with AHLs resulted in
      detection down to 0.01 ppm for 3-oxo-hexanoyl homoserine lactone (3-oxo C6-HSL)
      and 1 ppm for hexanoyl homoserine lactone (C6-HSL). Compared with liquid
      extraction methods use of SPE resulted in twofold and tenfold improvements in
      sensitivity, respectively.

PMID- 16082532
TI  - The inversion effect on gaze perception reflects processing of component
      information.
AB  - When faces are turned upside-down they are much more difficult to recognize than
      other objects. This "face inversion effect" has often been explained in terms of
      configural processing, which is impaired when faces are rotated away from the
      upright. Here we report a "gaze inversion effect" and discuss whether it is
      related to configural face processing of the whole face. Observers reported the
      gaze locations of photographed upright or inverted faces. When whole faces were
      presented, we found an inversion effect both for constant errors and observer
      sensitivity. These results were closely replicated when only the eyes were
      visible. Together, our findings suggest that gaze processing is largely based on
      component-based information from the eye region. Processing this information is
      orientation-sensitive and does not seem to rely on configural processing of the
      whole face.

PMID- 16082533
TI  - Neural correlates of conflict processing.
AB  - In this study we examined the neural correlates of conflict processing in the
      Stroop, counting, and digit-location tasks using event-related brain potentials
      (ERPs). The behavioral data revealed robust interference in response time and
      accuracy for all tasks. The interference effect for response time was greater in
      the Stroop task than the other tasks; in contrast, the interference effect for
      response accuracy was greater in the counting tasks than the other tasks. The
      N450 and sustained potential (SP) were elicited in each task. Partial least
      squares (PLS) analysis was used to examine the structural relationships between
      the ERPs, task design, and behavior. TaskPLS analysis revealed that the N450 and
      SP were associated with a single latent variable leading to the suggestion that a
      common set of neural generators was recruited during conflict processing across
      the tasks and that there were differences between ERPs related to early
      processing across the three tasks. BehavioralPLS analysis revealed that the
      amplitude of the SP was positively correlated with response time and accuracy,
      indicating that this modulation of the ERPs may be related to response selection
      rather than to conflict resolution.

PMID- 16082534
TI  - Firing rates of pallidal neurons are similar in Huntington's and Parkinson's
      disease patients.
AB  - According to the now classical basal ganglia-thalamocortical circuitry model, the
      chorea of Huntington's disease (HD) and the hypokinesia in Parkinson's disease
      (PD) are explained by a decrease in the inhibitory output (reduced firing rates)
      from the globus pallidus internus (GPi) in HD and increased output in PD.
      Differences between firing patterns might also be a factor contributing to the
      different symptoms, however. To test the predictions of the model we examined
      neuronal firing rates and patterns in two HD patients and 14 PD patients. Single
      cell, microelectrode recordings were obtained from awake patients undergoing
      stereotactic surgery for implantation of deep brain stimulating (DBS) electrodes
      in the GPi. The mean neuronal firing rate in the GPi of HD patients was 81.8+/
      4.3 Hz (mean+/-SEM), which was not significantly different from that in PD
      patients (89.9+/-3.0 Hz). Firing pattern analyses using measurements of burst
      index, coefficient of variation, and percentage participation of spikes in bursts
      revealed, however, that GPi neurons in HD patients fired in a more regular
      pattern (fewer "bursts") than in PD patients. These results suggest that the rate
      based model does not adequately explain the motor abnormalities present in the
      two HD patients studied. Furthermore, the findings did reveal a difference
      between firing patterns in the HD and PD groups, thereby supporting the role of
      altered firing patterns in the pathophysiology of these diseases.

PMID- 16082535
TI  - Functional imaging of changes in cerebellar activity related to learning during a
      novel eye-hand tracking task.
AB  - Coordination between the eyes and the hand is likely to be based on a process of
      motor learning, so that the interactions between the two systems can be
      accurately controlled. By using an unusual tracking task we measured the change
      in brain activation levels, as recorded with 3T functional magnetic resonance
      imaging (fMRI), between naive human subjects and the same subjects after a period
      of extended training. Initially the performance of the two groups was similar.
      One subject group was then trained in a synchronous, coordinated, eye-hand task;
      the other group trained with a 304 ms temporal offset between hand and eye
      tracking movements. After training, different patterns of performance were
      observed for the groups, and different functional activation profiles.
      Significant change in the relationship between functional activation levels and
      eye-hand task conditions was predominantly restricted to visuo-motor areas of the
      lateral and vermal cerebellum. In an additional test with one of the subject
      groups, we show that there was increased cerebellar activation after learning,
      irrespective of change in performance error. These results suggest that two
      factors contribute to the measured blood oxygen level-dependent (BOLD) signal.
      One declined with training and may be directly related to performance error. The
      other increased after training, in the test conditions nearest to the training
      condition, and may therefore be related to acquisition of experience in the task.
      The loci of activity changes suggest that improved performance is because of
      selective modified processing of ocular and manual control signals within the
      cerebellum. These results support the suggestion that coordination between eye
      and hand movement is based on an internal model acquired by the cerebellum that
      provides predictive signals linking the control of the two effectors.

PMID- 16082536
TI  - Cerebellar AMPA/KA receptor antagonism by CNQX inhibits vestibuloocular reflex
      adaptation.
AB  - Vestibuloocular reflex (VOR) performance and adaptation have been investigated
      during antagonism of cerebellar AMPA/quisqualate and kainate receptors (AMPA/KA)
      by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Injection of CNQX into the
      vestibulo-cerebellum of the goldfish before adaptation significantly inhibited
      and, at the highest dosage, completely prevented acquisition of adaptive reflex
      gain increases and decreases during a 3-h training period. Injection of CNQX
      before initiation of VOR adaptive training did not affect pre-adapted baseline
      performance of the reflex. Injection of CNQX, 1 to 2 h after the initiation of
      training did not alter the performance of adaptive gain increases that occurred
      before the injection. If injection of CNQX occurred at the end of adaptive
      training, there was an accelerated loss of the previously adapted gain changes
      during the retention period when the animal remained stationary in the dark. CNQX
      injection did not produce any permanent or long-term deficits, because goldfish
      could be retrained 48 h later to produce adaptive VOR gain changes similar to
      control animals. Thus, this work demonstrates that the AMPA/KA receptors located
      in the vestibulo-cerebellum of the goldfish are necessary for acquisition of
      short-term adaptive VOR gain increases and decreases. The deficit in adaptive
      capability was not the result of a deficit in performance, because CNQX did not
      inhibit an adaptive change that had already occurred as long as the adapting
      vestibular and visual stimulation continued. This adaptive performance could
      possibly be maintained by other glutamatergic (metabotropic) receptors located on
      the Purkinje cells. The retention of adapted gain increases and decreases after
      CNQX application was inhibited because AMPA/KA antagonism accelerated VOR gain
      loss after the completion of training when no vestibular or visual stimulation
      was present. Because the AMPA/KA receptors are located only in the molecular
      layer of the goldfish cerebellum, these results are, presumably, the result of
      AMPA/KA receptor antagonism at synapses located on the Purkinje cell dendrite
      tree.

PMID- 16082537
TI  - Effects of an orientation illusion on motor performance and motor imagery.
AB  - Although the effect of visual illusions on overt actions has been an area of keen
      interest in motor performance, no study has yet examined whether illusions have
      similar or different effects on overt and imagined movements. Two experiments
      were conducted that compared the effects of an orientation illusion on an overt
      posture selection task and an imagined posture selection task. In Experiment 1
      subjects were given a choice of grasping a bar with the thumb on the left side or
      right side of the bar. In Experiment 2 subjects were instructed to only imagine
      grasping the bar while remaining motionless. Subjects then reported which side of
      the bar their thumb had been placed in imagined grasping. Both the overt
      selection and imagined selection tasks were found to be sensitive to the
      orientation illusion, suggesting that similar visual information is used for
      overt and imagined movements, with both being sensitive to an orientation
      illusion. The results are discussed in terms of the visual processing and
      representation of real and imagined actions.

PMID- 16082538
TI  - Simultaneous genotyping of CYP2C9*2, *3, and 5' flanking region (C-1189T)
      polymorphisms in a Spanish population through a new minisequencing multiplex
      single-base extension analysis.
AB  - OBJECTIVE: To conduct a descriptive study on the prevalence of relevant
      cytochrome P450 2C9 (CYP2C9) polymorphisms--the *2, *3, and 5' flanking region (C
      1189T)--in a Spanish population using a new minisequencing fluorescent method
      through a multiplex single base extension (SBE) analysis. METHOD: The method
      simultaneously and accurately genotypes the CYP2C9 polymorphisms studied and is
      available as a commercial protocol (SNaPshot). Various strategies, including
      restriction fragment length polymorphism (RFLP) and Taqman, were used to validate
      the methodology. RESULTS: The frequencies of alleles CYP2C9*2 (12%) and *3 (6.2%)
      were similar to those described for other Caucasian populations. The frequency of
      allele t at the 5' flanking region was 62%, which is close to the percentage
      reported in Japanese and French populations. The four haplotypes inferred in our
      samples and their frequencies were consistent with those reported in other
      studies. CONCLUSION: Our results confirm previously reported Caucasian
      frequencies for the CYP2C9*2 and *3 alleles and, for the first time, provide data
      on the frequency of the CYP2C9 5' flanking region (C-1189T), a recently described
      polymorphism, in a Spanish population. The SBE technique detects unequivocally
      the three polymorphisms in a single reaction, which makes it suitable for the
      analysis of CYP2C9 in the many therapeutic situations in which it is involved.

PMID- 16082539
TI  - Initial treatment of hypertension and adherence to therapy in general practice in
      Italy.
AB  - BACKGROUND: Antihypertensive agents are among the most used therapeutic classes.
      The approach to the pharmacological treatment of hypertension is guided by
      international recommendations and adherence to treatment is known to result in
      effective prevention of cardiovascular risk. AIM: The aim of this study was to
      evaluate the pattern of use of antihypertensive agents in general practice in
      terms of drug choice for the initial treatment of hypertension and adherence to
      treatments among newly recruited patients. METHODS: We collected the data of all
      antihypertensive drugs prescribed by general practitioners (GPs) and reimbursed
      between January 1998 and December 2002 by a Local Health Authority of Emilia
      Romagna (Ravenna district, 350,000 inhabitants). We selected subjects aged 40
      years and older, permanently living in the area during the whole period of the
      study, who received their first prescription of antihypertensives between January
      and December 1999, with no prescription of antihypertensive agents in the
      previous year. For each patient, we documented the starting regimen and evaluated
      adherence to treatment in terms of persistence during the years (patients were
      defined persistent if they received at least one prescription per year) and in
      terms of daily coverage (patients were defined covered if they received an amount
      of drugs consistent with a daily treatment). Finally, switches or addition of
      other therapeutic classes during the 3-year period were identified. RESULTS: A
      cohort of 6,043 subjects receiving their first antihypertensive treatment in 1999
      was obtained. Regarding the starting regimen, monotherapies with angiotensin
      converting enzyme inhibitors (n = 1,597; 26%) or calcium channel blockers (n =
      1126; 19%) were the most frequently prescribed. Of the patients, 21% started with
      a drug combination regimen. Regarding adherence to treatment, 18% of the cohort
      received only one prescription throughout the 3 years, 13% received more than one
      prescription but stopped the therapy during the first year, 69% were persistent
      during the second year and 60% also during the third year. Only 34% were covered
      during the first year and 24% also during the second year, whereas only 20% of
      the patients resulted covered throughout the 3 years. Among persistent patients,
      41% maintained the same antihypertensive regimen throughout the 3 years, 25%
      added other drugs to the initial treatment and 34% switched to completely
      different regimens. CONCLUSIONS: Our findings reflect the lack of convergence
      among guidelines on the drug class(es) to be considered as first choice in the
      initial treatment of hypertension. Although an intervention in this field may
      have important implications in terms of cost savings, the ongoing debate does not
      allow us to draw definite conclusions on whether measures should be taken by the
      National Health Authority. However, the lack of adherence to antihypertensive
      treatment is undoubtedly a matter of concern for public health and should be
      addressed with appropriate interventions.

PMID- 16082540
TI  - Greater accuracy in positioning of the acetabular cup by using an image-free
      navigation system.
AB  - In a prospective and randomised clinical study, acetabular cups were implanted
      free-hand (control group n=22) or with computer assistance using an image-free
      navigation system (study group n=23). The cup position was determined
      postoperatively on pelvic CT. An average inclination of 42.3 degrees (range: 30
      degrees -53 degrees ; SD+/-7.0 degrees ) and an average anteversion of 24.0
      degrees (range: -3 degrees to 51 degrees ; SD+/-15.0 degrees ) were found in the
      control group, and an average inclination of 45.0 degrees (range: 40 degrees -50
      degrees ; SD+/-2.8 degrees ) and an average anteversion of 14.4 degrees (range: 5
      degrees -25 degrees ; SS+/-5.0 degrees ) in the computer-assisted study group.
      The deviations from the desired cup position (45 degrees inclination, 15 degrees
      anteversion) were significantly lower in the computer-assisted study group
      (p<0.001 each). While only 11/22 of the cups in the control group were within the
      Lewinnek safe zone, 21/23 of the cups in the study group were placed in this
      target region (p=0.003).

PMID- 16082541
TI  - Pre-formed articulating knee spacer in two-stage revision for the infected total
      knee arthroplasty.
AB  - We performed a prospective study to assess safety and effectiveness of a pre
      formed articulating spacer made of gentamicin-impregnated acrylic cement in the
      management of infected total knee arthroplasty. Twenty-one consecutive patients
      with unilateral deep infection were treated by two-stage revision in two centres.
      Two patients were excluded, and 19 patients remained available for assessment.
      The mean implantation time of the spacer was 12 weeks. The rehabilitation
      programme between stages consisted in early range of motion exercises and partial
      weight bearing. Mean follow-up after removal of the spacer and insertion of the
      final prosthesis was 24 (range, 12-43) months. No patient had recurrence of
      infection at the latest follow-up. The mean Knee Society functional score during
      spacer management was rated 75 points and was rated 84 points at the latest
      follow-up. No device-related complication was observed.

PMID- 16082542
TI  - Prediction of Charnley femoral stem aseptic loosening by early post-operative
      radiological features.
AB  - We describe the association between immediate post-operative radiological
      appearances and early aseptic failure of total hip replacement. Sixty-three hips
      were entered into the aseptic failure group and 138 into the control group.
      Alignment of the femoral stem was not associated with failure (p=0.283).
      Thickness of the cement mantle was associated with failure in Gruen zones 6
      (p=0.040) and 7 (p=0.003). A significant association for the presence of
      radiolucent lines was found for Gruen zones 3 (p=0.0001) and 5 (p=0.0001). Grade
      of cementation was associated with failure for Barrack grades C (p=0.001) and D
      (p=0.001). This study has demonstrated that easily applied radiological criteria
      can be used to identify 'hip arthroplasties at risk' from the immediate post
      operative radiograph.

PMID- 16082543
TI  - Arthroscopic synovectomy in haemophilic arthropathy of the knee.
AB  - From January 1996 to January 2001, arthroscopic synovectomies were performed in
      28 knees with haemophilic arthropathy. The mean follow-up period was 5 years and
      11 months. Six portals (two anterior, two suprapatellar, two posterior) and a
      posterior trans-septal portal were used in all cases. The average Hospital for
      Special Surgery (HSS) knee score increased from 56.4 to 71.5 points at the last
      follow-up. The average frequency of haemarthrosis reduced from five times per
      month before operation to once per month. The amount of factor replacement
      decreased from a mean of 4,633 U to 1,505 U. Progression of arthritis was
      observed radiographically in three cases at the last follow-up. An arthroscopic
      synovectomy of the knee using appropriate arthroscopic portals is a useful method
      in treating haemophilic patients as it decreases bleeding episodes, amount of
      factor replacement and knee pain.

PMID- 16082544
TI  - Vertebral fractures and concomitant fractures of the sternum.
AB  - From October 1996 to August 2001, 721 patients with vertebral fractures were
      admitted to our unit. Ten patients suffered from vertebral fractures and
      concomitant sternal fractures. The clinical notes and plain film radiographs of
      these patients were studied. The average age of the patients was 37 (20-69)
      years. Nine had been involved in road traffic accidents. Three patients had
      fractures of the cervical spine, six of the upper thoracic spine (T1-T6) and one
      had a lumbar spine fracture. The extra-thoracic fracture group included two
      patients with neurological compromise and two patients who were neurologically
      intact. The entire upper thoracic fracture group suffered neurological
      compromise, with four patients suffering complete neurological deficit. In
      addition, four of these patients suffered potentially life-threatening intra
      thoracic injuries. The relative severity of the neurological compromise and the
      attendant injuries in the upper thoracic fracture group offers compelling
      evidence in support of the "fourth column" theory, as expressed by Berg [Berg EE
      (1993), The sternal-rib complex. A possible fourth column in thoracic spine
      fractures. Spine 18(13):1916-1919].

PMID- 16082545
TI  - Effect of muscle dimensions on trabecular contractile performance under
      physiological conditions.
AB  - Multicellular cardiac muscles are widely used to study cardiac (patho-)physiology
      in vitro. One of the potential pitfalls of such experiments is that muscles with
      a large diameter have a larger diffusion barrier for transport of oxygen and
      waste products and can thus potentially form a hypoxic core. Although a
      sufficiently small muscle size is critical for obtaining unambiguous data, the
      relationship between muscle diameter and contractile performance specifically
      under near-physiological conditions remains unknown. Small uniform trabeculae of
      various diameters isolated from LBNF1 rats were stimulated at different
      temperatures (27.5-37.5 degrees C) and frequencies (1-8 Hz). Twitch contractions
      and rapid cooling contractures were used to assess contractile performance and SR
      Ca2+ load, respectively. We observed that at physiological frequencies and
      temperatures, contractile performance was clearly diminished in muscles with
      diameter >150 microm, likely due to the decreased rates of oxygen supply and
      waste removal. At room temperature slower contractions allow sufficient time for
      oxygen diffusion into the muscle core, and as a result the difference in
      contractile performance between the thin and thick muscles was less. Thus, in
      order to exclude adverse effects on contractile performance in multicellular
      myocardium under physiological conditions, it is essential that the preparations
      are of sufficient small diameter (<0.15 mm).

PMID- 16082546
TI  - The influence of movement cues on intermanual interactions.
AB  - In two experiments, we studied intermanual interactions in bimanual reversal
      movements and bimanual aiming movements. Targets were presented on a monitor or
      directly on the table on which the movements were produced. Amplitudes for each
      hand were cued symbolically or spatially either in advance of an imperative
      signal or simultaneous with it. In contrast to findings of Diedrichsen et al.
      (Psychological Science, 12, 493-498, 2001), reaction times for different
      amplitude movements were longer than for same-amplitude movements both for
      symbolic and spatial cues presented on the monitor and directly on the table.
      However, with symbolic cues the effect of the relation between target amplitudes
      was considerably stronger than with spatial cues, no matter where the cues were
      presented. Intermanual correlations of amplitudes, movement times, and reaction
      times were smaller with different than with same target amplitudes, and this
      modulation was more pronounced when targets and cues were presented on the
      monitor than when they were presented on the table. The findings are taken to
      suggest that the basic reaction-time disadvantage of different-amplitude
      movements results from interference between concurrent processes of amplitude
      specification. Additional factors like interference between concurrent processes
      of mapping cues on movement characteristics may add strongly to it.

PMID- 16082548
TI  - Risk factors for peritonitis in pediatric peritoneal dialysis: a single-center
      study.
AB  - Recent US registry data and a European multicenter study described increased risk
      of peritonitis in young children on peritoneal dialysis (PD). No underlying age
      specific risk factors could be defined in these reports. Therefore, we analyzed
      risk factors for peritonitis in children treated by PD as primary renal
      replacement therapy at the Kinderdialyse, Vienna, and particularly searched for
      age-specific aspects. Thirty children (15 boys, mean age 4.6 years) received PD
      [21 automated peritoneal dialysis (APD), nine continuous ambulatory peritoneal
      dialysis (CAPD)] for 13 months (3-49 months). During the total observation period
      of 395 dialysis months, 27 peritonitis episodes were diagnosed (1:14.6 months or
      0.82/patient per year). Of our population, 43% remained peritonitis free; seven
      patients suffered from more than one peritonitis episode. Ten potential risk
      factors [age, gender, PD modality, duration of PD, exit-site status, urine
      volume, residual glomerular filtration rate (GFR), Kt/V, normalized protein
      catabolic rate (nPCR), albumin] and four indices of peritonitis outcome
      (peritonitis incidence, peritonitis burden, risk of suffering more than one
      episode of peritonitis and chance of staying free from peritonitis) were
      analyzed. Our study identified six risk factors in univariate analysis, namely
      age, APD treatment, exit-site infections, low urinary volume, low residual GFR
      and low nPCR, which were significantly correlated with two or more of the outcome
      indices. Multivariate analysis identified exit-site infection and residual urine
      volume as strong independent predictors. In summary, our study identified several
      age-dependent and age-independent risk factors for peritonitis in pediatric PD.
      These data demonstrate that the risk for peritonitis in small children is not pre
      determined but might be open to therapeutic interventions, such as optimizing
      exit-site care, dialysis prescription and nutrition management.

PMID- 16082547
TI  - Assessing cardiovascular risk in children with chronic kidney disease. B-type
      natriuretic peptide: a potential new marker.
AB  - Elevated plasma B-type natriuretic peptide (BNP) level is a hallmark of altered
      left ventricular (LV) structure and function. Measurement of circulating BNP has
      proved to be a sensitive and specific diagnostic test for congestive heart
      failure (CHF) and coronary syndrome in adults. Further, BNP levels constitute a
      strong predictive marker for future cardiovascular (CV) events. In high CV risk
      populations, such as adults with hypertension or chronic kidney disease (CKD),
      increased BNP predicts CV morbidity and mortality in symptomatic or asymptomatic
      patients. However, caution is needed in interpreting plasma BNP levels, as they
      increase with both age and decreased renal function. Despite increasing evidence
      of the value of BNP in the medical literature in adults, data in children are
      limited to those with congenital heart disease. It is appropriate to analyze the
      potential application of this tool in children with CKD, a well-known factor for
      CV disease.

PMID- 16082550
TI  - Increased renal echogenicity in a preterm neonate. Kidneys with tubular dysplasia
      due to exposure to candesartan during pregnancy.

PMID- 16082551
TI  - Evaluation of acute pyelonephritis with DMSA scans in children presenting after
      the age of 5 years.
AB  - It is generally believed that infants are more susceptible to development of
      renal scarring after pyelonephritis than children over 5 years old. This view has
      led to differences in investigations and treatment according to age. The aim of
      this prospective study was to assess the occurrence of renal parenchymal lesion
      in children over 5 years admitted with a first-time symptomatic urinary tract
      infection (UTI). Between October 2000 and April 2002, 52 children aged over 5
      years who were admitted to our department with probable acute pyelonephritis
      (APN) and a positive urine culture were included in this study. All children
      received antibiotics for 14 days. During the acute phase of infection,
      scintigraphy with technetium-99m-labeled dimercaptosuccinic acid (DMSA) and
      ultrasonography (US) were done. Voiding cystourethrography (VCUG) was performed
      in all children early in the course of the illness, generally within 5-7 days of
      hospitalization. When scintigraphy showed renal parenchymal changes, repeat
      scintigraphy was done after at least 3 months to assess the progression of renal
      abnormalities. Of the 52 children with a first-time documented pyelonephritis,
      cortical scintigraphy showed renal lesion in 41 children (78.8%). US was normal
      in all children with normal renal scintigraphy, while it detected renal
      abnormalities in 16 of the 41 (39 %) with abnormal scintigraphy (p <0.0001).
      Topographic analysis of the 165 focal lesions showed that 42.4% were localized to
      the upper poles, 17.5% to the middle third, and 40% to the lower poles of the
      kidneys. Repeat scintigraphy showed persistent lesions corresponding to those on
      the initial scan in nine (28.2%) of the 32 children. Renal lesions had partly
      regressed in 23 (71.8%) of the patients who underwent repeat scintigraphy.
      Vesicoureteral reflux was observed in 13.4% of kidneys and renal parenchymal
      abnormalities were identified in 71.4% and 72.2% of renal units, respectively,
      with and without reflux ( p >0.05). In conclusion, our data did not confirm the
      conventional opinion that the risk of renal scarring after pyelonephritis is low
      in children over the age of 5 years. Our findings suggest that renal scintigraphy
      may be a more appropriate method of investigation than VCUG for evaluation of the
      children over 5 years with acute pyelonephritis. Additionally, the frequency of
      scintigraphic changes is high, and a strategy based exclusively on ultrasound
      findings would miss about 61% of the abnormal renal units. We recommend that all
      children, irrespective of age, will benefit from further investigations that
      might prevent or limit the development of scarring process and renal
      complications.

PMID- 16082553
TI  - Nephrolithiasis in a child with acute pyelonephritis. Ceftriaxone-induced
      nephrolithiasis and biliary pseudolithiasis.

PMID- 16082554
TI  - Complex media from processing of agricultural crops for microbial fermentation.
AB  - This mini-review describes the concept of the green biorefinery and lists a
      number of suitable agricultural by-products, which can be used for production of
      bioenergy and/or biochemicals. A process, in which one possible agricultural by
      product from the green crop drying industry, brown juice, is converted to a
      basic, universal fermentation medium by lactic acid fermentation, is outlined.
      The resulting all-round fermentation medium can be used for the production of
      many useful fermentation products when added a carbohydrate source, which could
      possibly be another agricultural by-product. Two examples of such products
      polylactic acid and L-lysine-are given. A cost calculation shows that this
      fermentation medium can be produced at a very low cost approximately 1.7 Euro
      cent/kg, when taking into account that the green crop industry has expenses
      amounting to 270,000 Euro/year for disposal of the brown juice. A newly built
      lysine factory in Esbjerg, Denmark, can benefit from this process by buying a low
      price medium for the fermentation process instead of more expensive traditional
      fermentation liquids such as corn steep liquor.

PMID- 16082555
TI  - Substrate specificity and transglycosylation catalyzed by a thermostable beta
      glucosidase from marine hyperthermophile Thermotoga neapolitana.
AB  - The gene encoding beta-glucosidase of the marine hyperthermophilic eubacterium
      Thermotoga neapolitana (bglA) was subcloned and expressed in Escherichia coli.
      The recombinant BglA (rBglA) was efficiently purified by heat treatment at 75
      degrees C, and a Ni-NTA affinity chromatography and its molecular mass were
      determined to be 56.2 kDa by mass spectrometry (MS). At 100 degrees C, the enzyme
      showed more than 94% of its optimal activity. The half-life of the enzyme was 3.6
      h and 12 min at 100 and 105 degrees C, respectively. rBglA was active toward
      artificial (p-nitrophenyl beta-D: -glucoside) and natural substrates (cellobiose
      and lactose). The enzyme also exhibited activity with positional isomers of
      cellobiose: sophorose, laminaribiose, and gentiobiose. Kinetic studies of the
      enzyme revealed that the enzyme showed biphasic behavior with p-nitrophenyl beta
      D: -glucoside as the substrate. Whereas metal ions did not show any significant
      effect on its activity, dithiothreitol and beta-mercaptoethanol markedly
      increased enzymatic activity. When arbutin and cellobiose were used as an
      acceptor and a donor, respectively, three distinct intermolecular transfer
      products were found by thin-layer chromatography and recycling preparative high
      performance liquid chromatography. Structural analysis of three arbutin transfer
      products by MS and nuclear magnetic resonance indicated that glucose from
      cellobiose was transferred to the C-3, C-4, and C-6 in the glucose unit of
      acceptor, respectively.

PMID- 16082556
TI  - Prevalence of low central bone mineral density in a Bulgarian female referral
      population: a pilot study.
AB  - Osteoporosis is one of the most important health problems among elderly women.
      The prevalence of central osteoporosis in Bulgaria is still unknown. We tried to
      retrospectively determine the prevalence of osteopenia and osteoporosis at the
      spine and hip in a female referral population. Bulgarian women (2,600) aged group
      25-87 years referred for bone densitometry screening were included. Information
      about known risk factors for low bone mass was recorded. Bone mineral density
      (BMD) was measured by dual-energy X-ray absorptiometry (Hologic QDR 4500 A) at
      the lumbar spine (2,547 participants, 1,954 of whom were postmenopausal) and left
      hip (723 participants, 605 of whom were postmenopausal). T-scores were calculated
      from Hologic-provided and own Bulgarian peak BMD data (the latter based on 122
      healthy premenopausal 25- to 39-year-old women). Peak lumbar spine BMD was 0.994
      g/cm2 (SD 0.095 g/cm2), and thus lower than the manufacturer-provided value of
      1.047 g/cm2. The peak BMD of the total hip was 0.959 g/cm2 (SD 0.129 g/cm2) and
      thus higher than the manufacturer-provided BMD of 0.942. T-scores differed
      according to the database used. The osteoporosis threshold of -2.5 SD was reached
      at the spine in the age group 70-74 years. Left hip T-scores showed a much slower
      decline with age. In women aged 50 and older the prevalence of osteoporosis
      reached 37.31% at the spine, and 16.14% at the left hip. Osteopenia was found in
      39.74% at the spine and in 65.57% at the total hip. This is the first Bulgarian
      study looking for the prevalence of central osteoporosis in a female referral
      population. It may become the starting point for future epidemiological work.

PMID- 16082557
TI  - Seasonal variation of chromophore composition in the eye of the Japanese dace,
      Tribolodon hakonensis.
AB  - The relationship between seasonal variation and the effect of several different
      environmental factors on chromophore composition was investigated in the eye of
      the Japanese dace, Tribolodon hakonensis which lives either in rivers or in the
      sea. Eyes obtained from river and sea populations had both retinal (A1) and 3,4
      didehydroretinal (A2) all through the year but the ratio of these chromophores
      showed seasonal variation the relative amount of A2 was higher in winter and
      lower in summer. Besides seasonal variation, A2 showed marked differences
      depending on habitat: the highest proportion of A2 was 67% in January and the
      lowest 13% in July, in the river population, whereas in the sea population the
      highest and the lowest values were only 30 and 6%, respectively, during the same
      months. The seasonal variation in gonadosomatic index showed no correlation to
      variations in A2 proportion, and the maximum difference in water temperature
      between summer and winter was ca. 15 degrees C for both habitats. Because
      spectral conditions at the locations of capture of both river and sea populations
      were similar, we conclude that Japanese dace eyes are affected by exogenous
      factors related to differences between freshwater and seawater environments.

PMID- 16082558
TI  - Repeatability and reproducibility of optic nerve head topography using the
      retinal thickness analyzer.
AB  - OBJECTIVE: The objective was to determine the reproducibility and repeatability
      of topographic disk parameters with the retinal thickness analyzer (RTA).
      METHODS: Thirty-nine eyes of 39 healthy subjects were included. Three observers
      performed three consecutive measurements of optic disk topography independently.
      Combined repeatability (intra-observer component of variability) and
      reproducibility (inter-observer component of variability, R and R) was assessed
      by variance component analysis. RESULTS: Six topographic parameters (disk area,
      cup area, cup volume, mean cup depth, maximum depth, and cup shape measure)
      revealed an acceptable repeatability and reproducibility expressed as the
      percentage of the total measurement variability (range 17.6-28.4%). The average
      reproducibility and repeatability of all optic disk parameters measured using the
      RTA was not acceptable (combined R and R = 33.4%). CONCLUSIONS: Repeatability and
      reproducibility of the optic disk topography analysis using the RTA reveals a
      high variation, and should, therefore, be interpreted carefully for glaucoma
      diagnosis and for monitoring the disease.

PMID- 16082559
TI  - Progressive cone dystrophy with deutan genotype and phenotype.
AB  - PURPOSE: To study the electroretinographic signals originating in the long
      wavelength-sensitive (L) and middle-wavelength-sensitive (M) cone pathways by
      means of large-field and multifocal cone type-specific electroretinograms (ERGs)
      in a patient with progressive cone dystrophy. METHODS: A 65-year-old male patient
      with colour vision disturbances (age at onset 10 years), loss of visual acuity
      (14 years), and central visual field defects (40 years) was investigated. Large
      field flicker-ERG responses to stimuli that exclusively modulated the L-cones or
      the M-cones, or the two simultaneously (both in-phase and in counter-phase), were
      measured. Short-wavelength-sensitive (S) cones were not modulated. Multifocal
      ERGs (mfERGs) were also recorded, with a pattern-reversing display that modulated
      only the L- or the M-cones at equal cone contrasts and average quantal catches.
      Genetic analysis of L- and M-pigment genes was performed on genomic DNA isolated
      from peripheral venous blood. RESULTS: The patient showed a normal rod-driven ERG
      but reduced cone-driven electroretinographic amplitudes with normal implicit
      times in the International Society for Clinical Electrophysiology of Vision
      (ISCEV) standard ERG. The large-field flicker-ERG responses to pure L-cone
      modulation were significantly above noise level but were substantially reduced in
      comparison with both normal trichromatic subjects and (otherwise normal)
      deuteranopes. The L-cone driven electroretinographic implicit times and phases
      were within normal limits. The M-cone driven electroretinographic responses were
      not detectable. A model fit of all the L- and M-cone driven flicker-ERG data
      revealed that the responses were exclusively driven by the L-cones. Consistently,
      the cone type-specific mfERGs showed severely reduced but detectable responses to
      L-cone-isolating stimuli. The M-cone driven multifocal-ERG responses were
      undistinguishable from noise. The L- and M-pigment gene array consisted of only a
      single L-pigment gene. The complete coding sequence of this gene was determined
      and showed no abnormality. CONCLUSIONS: This patient exhibits a coincidence of
      progressive cone dystrophy and deuteranopia. The molecular genetic data of the
      L/M-pigment gene array is consistent with the deutan phenotype. It cannot be
      excluded that the rearrangement of the X-chromosome pigment gene array is
      responsible for the cone dystrophy in this patient. It is, however, suggested
      that the dichromacy and the cone dystrophy have different and independent genetic
      origins.

PMID- 16082560
TI  - Loss of p16INK4A expression is associated with allelic imbalance/loss of
      heterozygosity of chromosome 9p21 in microdissected synovial sarcomas.
AB  - Deletions of the short arm of chromosome 9 have been observed in many tumours and
      cell lines. This chromosomal region is frequently targeted during malignant
      transformation because it contains at least two known tumour suppressor genes:
      p16(INK4) and p15(INK4B). p16(INK4A) acts as a negative cell cycle regulator by
      inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma
      protein and therefore block the progression of the cell cycle from G1 to S phase.
      The role of p16(INK4A) in the development of synovial sarcoma has not been
      comprehensively investigated. Ten samples of synovial sarcomas were examined for
      allelic imbalance/loss of heterozygosity (AI/LOH) of the 9p region and p16
      protein expression. DNA was isolated from microdissected sections of normal and
      tumour cells, amplified by polymerase chain reaction and analysed for AI/LOH by
      using six microsatellite markers that map to the 9p region. Immunohistochemistry
      for p16 expression was done. AI/LOH with at least one microsatellite marker on
      9p21 was detected in six of ten samples. The most frequent allelic deletions were
      observed within the coding sequence of p16(INK4A). Loss of p16 immunoreactivity
      was detected in eight samples, six of which showed evidence of alterations at
      9p21 region. These findings suggest a possible role of loss of p16(INK4A) in the
      development of synovial sarcoma.

PMID- 16082561
TI  - Controlling for anthropogenically induced atmospheric variation in stable carbon
      isotope studies.
AB  - Increased use of stable isotope analysis to examine food-web dynamics, migration,
      transfer of nutrients, and behavior will likely result in expansion of stable
      isotope studies investigating human-induced global changes. Recent elevation of
      atmospheric CO2 concentration, related primarily to fossil fuel combustion, has
      reduced atmospheric CO2 delta13C (13C/12C), and this change in isotopic baseline
      has, in turn, reduced plant and animal tissue delta13C of terrestrial and aquatic
      organisms. Such depletion in CO2 delta13C and its effects on tissue delta13C may
      introduce bias into delta13C investigations, and if this variation is not
      controlled, may confound interpretation of results obtained from tissue samples
      collected over a temporal span. To control for this source of variation, we used
      a high-precision record of atmospheric CO2 delta13C from ice cores and direct
      atmospheric measurements to model modern change in CO2 delta13C. From this model,
      we estimated a correction factor that controls for atmospheric change; this
      correction reduces bias associated with changes in atmospheric isotopic baseline
      and facilitates comparison of tissue delta13C collected over multiple years. To
      exemplify the importance of accounting for atmospheric CO2 delta13C depletion, we
      applied the correction to a dataset of collagen delta13C obtained from mountain
      lion (Puma concolor) bone samples collected in California between 1893 and 1995.
      Before correction, in three of four ecoregions collagen delta13C decreased
      significantly concurrent with depletion of atmospheric CO2 delta13C (n > or = 32,
      P < or = 0.01). Application of the correction to collagen delta13C data removed
      trends from regions demonstrating significant declines, and measurement error
      associated with the correction did not add substantial variation to adjusted
      estimates. Controlling for long-term atmospheric variation and correcting tissue
      samples for changes in isotopic baseline facilitate analysis of samples that span
      a large temporal range.

PMID- 16082562
TI  - Nonparasitic Nematoda provide evidence for a linear response of functionally
      important soil biota to increasing livestock density.
AB  - Soil acidity, nutrient availability and livestock density have a major influence
      on the belowground ecological community. As fast decomposition rates are due
      mostly to bacterial-based pathways and slower decomposition rates mostly to
      fungal-based pathways, it is helpful to condense empirical information in the so
      called Nematode Channel Ratio (NCR). The NCR is shown to be a good indicator of
      efficiency in soil decomposition processes. We argue that in intensive
      agroecosystems, other fungivore members of the decomposer food web may outcompete
      the hyphal-feeding nematodes. We demonstrate how the NCR can be used to set
      ecological standards for sustainable use of the soil in agroecosystems. To
      summarize the interactions between the microbial resources and the decomposer
      nematofauna according to increasing land management, we propose the use of the
      fifth percentile as proxy for a sustainable environmental quality of grasslands
      on sandy soils, and the NCR mean as the upper threshold for low-stocked farms.

PMID- 16082564
TI  - Microsatellite evolution in the mitochondrial genome of Bechstein's bat (Myotis
      bechsteinii).
AB  - Being highly polymorphic, microsatellites are widely used genetic markers. They
      are abundant throughout the nuclear genomes of eukaryotes but rare in the
      mitochondrial genomes (mtDNA) of animals. We describe a short but highly
      polymorphic AT microsatellite in the mtDNA control region of Bechstein's bat and
      discuss the role of mutation, genetic drift, and selection in maintaining its
      variability. As heteroplasmy and hence mutation rate were positively correlated
      with repeat number, a simple mutation model cannot explain the observed frequency
      distribution of AT copy numbers. Because of the unimodal distribution of repeat
      numbers found in heteroplasmic individuals, single step mutations are likely to
      be the predominant mechanism of copy number alternations. Above a certain copy
      number (seven repeats), deletions of single dinucleotide repeats seem to be more
      common than additions, which results in a decrease in frequency of long alleles.
      Heteroplasmy was inherited from mothers to their offspring and no evidence of
      paternal inheritance of mitochondria was found. Genetic differences accumulated
      with more distant ancestry, which suggests that microsatellites can be useful
      genetic markers in population genetics.

PMID- 16082565
TI  - Common evolutionary origin and birth-and-death process in the replication
      independent histone H1 isoforms from vertebrate and invertebrate genomes.
AB  - The H1 histone multigene family shows the greatest diversity of isoforms among
      the five histone gene families, including replication-dependent (RD) and
      replication-independent (RI) genes, according to their expression patterns along
      the cell cycle and their genomic organization. Although the molecular
      characterization of the RI isoforms has been well documented in vertebrates,
      similar information is lacking in invertebrates. In this work we provide evidence
      for a polyadenylation signature in the Mytilus "orphon" H1 genes similar to the
      polyadenylation characteristic of RI H1 genes. These mussel genes, together with
      the sea urchin H1delta genes, are part of a lineage of invertebrate "orphon" H1
      genes that share several control elements with vertebrate RI H1 genes. These
      control elements include the UCE element, H1-box and H4-box. We provide evidence
      for a functional evolution of vertebrate and invertebrate RI H1 genes, which
      exhibit a clustering pattern by type instead of by species, with a marked
      difference from the somatic variants. In addition, these genes display an
      extensive silent divergence at the nucleotide level which is always significantly
      larger than the nonsilent. It thus appears that RI and RD H1 isoforms display
      similar long-term evolutionary patterns, best described by the birth-and-death
      model of evolution. Notably, this observation is in contrast with the theoretical
      belief that clustered RD H1 genes evolve in a concerted manner. The split of the
      RI group from the main RD group must therefore have occurred before the
      divergence between vertebrates and invertebrates about 815 million years ago.
      This was the result of the transposition of H1 genes to solitary locations in the
      genome.

PMID- 16082566
TI  - A novel possible mechanism for the genesis of genomic duplications and its
      experimental test.
AB  - Duplication of genomic regions is an important biological process associated with
      the appearance of gene families, the origin of alternative splicing, and the
      etiopathogenesis of genetic diseases. Different mechanisms for the genesis of
      duplications have been suggested, based mainly on structural analyses. However,
      experimental confirmation of those mechanisms is scarce, mostly because of a lack
      of information about the circumstances that triggered the rearrangements. Here, I
      characterize a duplication of about 300 kbp (kilobase pairs) that occurred in the
      course of a gene targeting experiment. Considering the structure of the locus and
      the triggering event, I suggest a likely mechanism for the genesis of this
      duplication which involves anomalous processing of contiguous Okazaki fragments
      during lagging strand replication. Most importantly, I provide experimental
      evidence to substantiate that the proposed mechanism can indeed lead to
      duplication of genomic segments. The model presented represents a novel
      mechanistic pathway that can explain a variety of rearrangements, including
      genomic tandem duplications and deletions.

PMID- 16082567
TI  - Evolution of a unique mitotype-specific protein-coding extension of the
      cytochrome c oxidase II gene in freshwater mussels (Bivalvia: Unionoida).
AB  - A unique mode of mitochondrial DNA inheritance, designated doubly-uniparental
      inheritance (DUI), occurs in three bivalve subclasses (Pteriomorpha: Mytiloida,
      Palaeoheterodonta: Unionoida, Heterodonta: Veneroida), indicating that DUI may be
      a widespread phenomenon among bivalves. In mytiloids, breakdown of this pattern
      of inheritance (gender-switching) is observed in natural populations and in a
      phylogenetic context. In contrast, gender-switching has not occurred during the
      evolutionary history of unionoids. Here we present sequences for the male (M) and
      female (F) mitotypes from an additional 8 species of Unionoida. Consistent with
      previous observations, the M and F mitotypes of all species form reciprocally
      monophyletic clades supporting the hypothesis of taxon-specific rates of gender
      switching. Coinciding with the absence of gender-switching is an approximately
      185 codon extension of the cytochrome c oxidase II (MTCO2) locus in the male
      genome. The extension is present in all 12 unionoid species examined, including a
      representative of the family Margaritiferidae, indicating that this protein
      coding polymorphism originated > or = 200 MYBP: . Although the extension is well
      conserved in length among 11 of the 12 species, one taxon has a significantly
      shortened extension. Lastly, examination of the rates and patterns of
      substitution indicate that the extension is evolving under relaxed purging
      selection, a pattern inconsistent with the conserved nature of MTCO2 or any
      cytochrome c oxidase locus.

PMID- 16082569
TI  - No net loss of fish habitat: a review and analysis of habitat compensation in
      Canada.
AB  - The achievement of No Net Loss (NNL) through habitat compensation has rarely been
      assessed in Canada. Files relating to 124 Fisheries Act Section 35(2)
      authorizations issued by Fisheries and Oceans Canada for the harmful alteration,
      disruption, and destruction of fish habitat (HADD) were collected and reviewed.
      Data extracted from these files were pooled and analyzed to provide an indication
      of the types of HADDs that have been authorized in Canada, what habitats have
      been affected, and what habitat management approaches have been used when
      compensating for HADDs and monitoring and ensuring the success of the
      compensation. Determinations regarding the effectiveness of habitat compensation
      in achieving NNL were made. Impacts to 419,562 m2 of fish habitat from the 124
      authorized HADDs were offset by 1,020,388 m2 of compensatory habitat. Eighty
      percent of the authorizations had compensation ratios (compensation area:HADD
      area) of 2:1 or less, and 25% of the authorizations had a compensation ratio that
      was less than 1:1. In-channel and riparian habitat were the most frequently
      impacted habitats. Urban development and roads and highways resulted in the
      greatest areal loss of habitat. The compensation option that was most often
      selected was the creation of in-kind habitat. The mean duration of post
      construction monitoring programs was 3.7 years. Determinations of NNL could only
      be made for 17 authorizations as a result of poor proponent compliance with
      monitoring requirements and the qualitative assessment procedures used by the
      monitoring programs. Adequate resources, proper training, and standardized
      approaches to data management and monitoring programs are required to ensure that
      the conservation goal of NNL can be achieved in Canada.

PMID- 16082570
TI  - Plasmatic [corrected] factor XIII reduces severe pleural effusion in children
      after open-heart surgery.
AB  - Chylous effusions frequently occur after cardiac surgery due to severe damage to
      the lymphatic system, thus indicating that the insertion of a chest tube may be
      necessary. Factor XIII (FXIII) is discussed as being essential for wound healing.
      The aim of this retrospective study was to evaluate whether the application of a
      single dose of FXIII results in a reduced amount of pleural effusion, leading to
      an earlier release of patients from the hospital. The cases of 40 children with
      severe chylous effusions after open-heart surgery were examined. Twenty patients
      received FXIII and were compared to 20 age- and weight-matched patients who did
      not receive FXIII. Major parameters included the amount of effusion before and 1
      and 3 days after the application of FXIII; the duration of chest tubes; the total
      amount of fluid loss via drainage; and the period of hospitalization. FXIII
      levels in plasma showed an inverse correlation with fluid loss. After application
      of a single dose of FXIII, a significant reduction of pleural effusion within the
      first 24 hours was detected. However, no difference was observed between the two
      groups when comparing the total amount of pleural effusions within the first 72
      hours. Finally, the duration of hospitalization did not differ between the FXIII
      treated and the control group. A single application of FXIII rapidly reduces the
      amount of chylous effusions in the early period after open-heart surgery. This
      effect is detectable only for 24 hours after the treatment and does not alter the
      further clinical outcome. Prospective clinical trials are warranted to determine
      if repeated application or a higher dose of FXIII may improve the clinical
      outcome of chylous leakages in children after open-heart surgery.

PMID- 16082571
TI  - Regression of cardiac enzyme and ventriculocoronary communication in an infant
      with pulmonary atresia and intact ventricular septum after radiofrequency
      valvulotomy and valvuloplasty.
AB  - I report on a 3-month-old infant with pulmonary atresia-intact ventricular septum
      and ventriculocoronary communication (VCC) who underwent percutaneous
      radiofrequency valvulotomy and valvuloplasty (RFVV). The patient's cardiac
      troponin-I, creatine kinase (CK), and myocardial fraction of (CK-MB) were
      elevated before RFVV and were gradually regressed to normal levels 12 days after
      RFVV. The VCC disappeared after RFVV. The transvalvular pressure gradients across
      the pulmonary valve were less than 30 mmHg in the follow-up echocardiography at 4
      12 months of age. Oxygen saturation was approximately 90% in room air.
      Dipyridamole-thallium myocardial scintigraphy showed positive reperfusion over
      the apex and interventricular septum.

PMID- 16082572
TI  - Quantification of periprosthetic valve leakage with multiple regurgitation jets
      by magnetic resonance imaging.
AB  - A patient with aortic prosthetic valve endocarditis required replacement of the
      prosthesis, After initial recovery, his left ventricular function gradually
      declined and echocardiography revealed minor paravalvular leakage and a cavern
      around the prosthesis. Magnetic resonance imaging was performed, flow-imaging and
      volume-based measurements showed high-grade paravalvular leakage of 45 and 58%
      regurgitant fraction, respectively. Intraoperatively, the dehiscence of more than
      half of the circumference of the aortic prosthesis was seen. This study shows
      that MRI can accurately assess even periprosthetic valve leakage with multiple
      regurgitation jets.

PMID- 16082573
TI  - Advanced embolization techniques.
AB  - The techniques of transcatheter embolization of unwanted blood vessels in
      patients with congenital heart disease have evolved considerably during the past
      25 years. There are many different anatomical lesions requiring different
      approaches and devices. The main types of devices used can be classified into
      particles, coils, and plugs. It is important for the operator to be familiar with
      a range of these devices. The results of transcatheter embolization are usually
      excellent, and technical problems and complications can usually be overcome by
      attention to detail and persistence. The types of devices in common use and their
      clinical applications are discussed.

PMID- 16082574
TI  - Challenges encountered during closure of patent ductus arteriosus.
AB  - Transcatheter closure of patent ductus arteriosus (PDA) was one of the first
      interventions established in invasive cardiology and is now more than 30 years
      old. The challenges for successful closure with the first devices in children
      consisted of handling the rather large introducer sheaths and stiff application
      systems. Today, interventional closure can be performed with different types of
      plugs, occluders, and coils. Thus, beyond infancy, transcatheter closure can be
      successfully performed in almost all cases. Challenging from the technical
      standpoint can be the closure of window-type ducts, in which excessive protrusion
      of the device into the descending aorta should be avoided, as well as the closure
      of tubular ducts, in which secure anchoring of one or more devices in the vessel
      can be very difficult. For the combination of a coarctation and an open duct,
      different strategies can be considered. In selected cases, use of a covered stent
      can be helpful. From the physiological standpoint, open ducts in patients with
      pulmonary hypertension with or without concomitant congenital heart diseases can
      be challenging because testing of vasoreactivity with temporarily blocked duct
      and the option of subsequent treatment with vasodilators may be necessary prior
      to making the decision whether the patient may benefit from definitive duct
      occlusion or not. Large ducts in infants less than 8 kg can be difficult to treat
      due to a relative mismatch of introducers, plugs, or occluders to the small
      anatomic dimensions. The implantation of multiple coils can be associated with a
      higher risk of device embolization. Unfortunately, for the large group of preterm
      infants with very low body weights and large ducts of tubular shape there is
      currently no standardized interventional therapy available.

PMID- 16082575
TI  - Embolization and transcatheter retrieval of coils and devices.
AB  - Embolizations of coils and devices are well-known complications of transcatheter
      procedures performed in order to occlude extracardiac or intracardiac shunts. A
      review of the literature and of our experience was performed to provide a
      succinct review of existing transcatheter retrieval techniques. After
      embolization of a coil or device, the appropriate initial procedure involves
      repositioning of the coil or device using a snare or bioptome to a location where
      harm to the patient is minimized. The subsequent retrieval technique depends on
      the characteristics of the coil or device involved. Coils may be retrieved using
      a bioptome or a snare. Devices must be snared, often in specific places. Both may
      be pulled into long or short, appropriately sized retrieval sheaths. To minimize
      potential morbidities associated with these retrievals and to maximize efficacy
      of retrieval, operators performing transcatheter coil or device occlusions must
      be familiar with retrieval techniques.

PMID- 16082576
TI  - Catheter interventions for congenital heart disease in third world countries.
AB  - The term "Third World" loosely encompasses a group of middle- and low-income
      countries. Considerable differences exist in health care delivery and health
      indices among these countries. The vast majority of children in the Third World
      do not have health insurance for congential heart disease (CHD). Catheter
      interventions for CHD are expensive because of installation costs of expensive
      biplane equipment, the requirement of dedicated personnel, and the need to stock
      a large inventory of expensive hardware. As a result, many catheter intervention
      procedures are beyond the reach of the average patient in the developing world.
      The following cost-effective strategies have evolved in selected institutions
      that have attempted to perform catheter interventions for CHD at an affordable
      cost: sharing of space, equipment, and support personnel with a busy adult
      cardiology program; use of single plane equipment; the development of sedation
      protocols to reduce the need for anesthesiologists; strategies to reduce
      procedure time; reuse of hardware through ethylene oxide sterilization;
      improvisations to use adult hardware items for CHD interventions; judicious case
      selection; and improvised alternatives to occlusive devices. These strategies may
      help reduce costs and allow a larger proportion of patients in developing
      countries with CHD to undergo interventions. However, the safety of these
      strategies and the cost savings need to be carefully evaluated prospectively.

PMID- 16082577
TI  - Catheter closure of congenital muscular ventricular septal defects.

PMID- 16082578
TI  - Percutaneous closure of perimembranous ventricular septal defects with the
      eccentric Amplatzer device: multicenter follow-up study.
AB  - Using an Amplatzer membranous eccentric occluder, 186 patients with an average
      weight of 43.5 kg (range 12.5-77) underwent attempted catheter closure of a
      perimembranous venricular septal defect (PMVSD). Their age ranged from 3 to 51
      years, with the an average age being 15.9 years. The patients were divided into
      three groups according to morphology of PMVSD: 106 patients with single PMVSD, 63
      patients with single PMVSD with aneurysmatic formation, and 17 patients with
      multiple VSD with aneurysmatic formation. Using angiography, PMVSDs were measured
      to be between 2.5 and 12 mm, with an average of 5.1 mm. In the third group of
      patients, we did not measure the size of PMVSD and a device was selected
      according to the size of entry to the aneurysm. The device was successfully
      implanted in all patients. The immediate closure rate was 90% in the first group,
      increasing to 100% at 1 month and remained at that level during follow-up. The
      immediate closure rate in the second group was 98% and remained the same during
      follow-up. The immediate closure rate in the third group was 89% and during 1
      year of follow-up remained the same. There was no clinical evidence of hemolysis
      and no incidence of device embolization or bacterial endocarditis after
      implantation. Before the procedure, all patients showed normal electrocardiogram
      (ECG) or left ventricle enlargement. After the procedure (at least 3 months
      later) ECG showed left anterior hemiblock (LAH) in nine patients, complete right
      bundle branch block in eight patients, and incomplete right bundle branch block
      in seven patients. A complete heart block (CHB) developed in 2 patients after the
      procedure (1.07%). The first patient developed LAH immediately after closure and
      CHB within 24 hours, The heart rate was 28 beats per minute. After treatment with
      steroids and atropine, CHB changed to sinus rhythm with LAH within 2 months. One
      year later, the ECG revealed the same findings. The second patient developed CHB
      immediately after the procedure and was on temporary pacing for 1 week. After 1
      month, the patient recovered to sinus rhythm and ECG showed LAH.

PMID- 16082579
TI  - Radial plication in concentric mastopexy.
AB  - Concentric mastopexy presents many challenges to the plastic surgeon, especially
      when breast augmentation is part of the treatment plan. Radial plication is a
      reproducible and accurate technique for elevating the nipple-areolar complex and
      shaping the breast mound. Patient selection is important to the success of the
      radial plication procedure and concentric mastopexy in general. Although most
      surgeons agree that patients with smaller degrees of nipple ptosis and smaller
      breasts have better results than patients with greater degrees of nipple ptosis
      and larger breasts, there has never been an algorithm for patient selection.
      Regnault's classification of breast ptosis addresses the degree of nipple ptosis,
      but no consideration is given to breast volume. Radial placation proved to be a
      valuable tool in the treatment of 87 patients undergoing concentric mastopexy in
      the author's practice over the past 30 months. An algorithm addressing degrees of
      breast ptosis and breast volume is provided. The plastic surgeon can anticipate
      gratifying results if the algorithm provided is incorporated into his or her
      patient selection for concentric mastopexy. The concentric mastopexy technique is
      similar to the tailor tack procedure for standard mastopexy, allowing the plastic
      surgeon to mold and shape the breast before making a critical incision.

PMID- 16082580
TI  - Increase of the behavioral response to kairomones by the parasitoid wasp
      Leptopilina heterotoma surviving insecticides.
AB  - Hymenopterous parasitoids are key species involved in the regulation of insect
      populations. Kairomone perception is an important step leading to host
      parasitization. The massive use of insecticides induces environmental pollution
      that can interact with the reproduction of parasitoids. In this work, we have
      determined the sublethal effects of two insecticides, an organophosphorus
      (chlorpyrifos) and a pyrethroid (deltamethrin), on the arrestment, by host
      kairomones, of female parasitoids surviving an LD 20 for 24 h. The behavior of
      the parasitoids has been recorded with a video-computerized system. The analysis
      of the behaviors in control conditions versus exposed to an LD 20 have shown that
      both insecticides significantly increased the arrestment of parasitoids by
      kairomones. This increase was not followed up by a modification of the kinetics
      of the behavior. In both control and exposed conditions, parasitoids regularly
      increased their residence time on the kairomone patch indicating that no
      saturation to kairomones had occurred. In a field situation where hosts could be
      scarce, this increase in arrestment could be advantageous for parasitoids by
      increasing their host finding.

PMID- 16082581
TI  - Characterization and primer development for amplification of chloroplast
      microsatellite regions of Fraxinus excelsior.
AB  - This study reports the characterization of chloroplast DNA (cpDNA) variation of
      Fraxinus excelsior at five loci and the successful development of primer pairs
      for the amplification of three of these containing mononucleotide
      microsatellites. We detected high levels of haplotype variation among provenances
      of Fraxinus around Europe and within Ireland.

PMID- 16082582
TI  - Clinical aspects of intraductal papillary mucinous neoplasm of the pancreas.
AB  - Intraductal papillary mucinous neoplasm (IPMN) is a spectrum of neoplasia in the
      pancreatic duct epithelium characterized by cystic dilation of the main and/or
      branch pancreatic duct. According to the site of involvement IPMNs are classified
      into three categories, i.e., main duct type, branch duct type, and combined type.
      Most branch duct IPMNs are benign, whereas the other two types are often
      malignant. A large size of branch duct IPMN and marked dilation of the main
      pancreatic duct indicate the presence of adenoma at least. The additional
      existence of large mural nodules increases the possibility of malignancy in all
      types. Of recent interest is the relatively high prevalence of synchronous and/or
      metachronous malignancy in various organs, including the pancreas. The prognosis
      is favorable after complete resection of benign and noninvasive malignant IPMNs.
      Malignant IPMNs acquiring aggressiveness after parenchymal invasion necessitate
      adequate lymph node dissection. On the other hand, asymptomatic branch duct IPMNs
      without mural nodules can be observed without resection for a considerably long
      time. This review addresses available data, current understanding, controversy,
      and future directions.

PMID- 16082583
TI  - Esophageal melanosis, an endoscopic finding associated with squamous cell
      neoplasms of the upper aerodigestive tract, and inactive aldehyde dehydrogenase-2
      in alcoholic Japanese men.
AB  - BACKGROUND: Esophageal melanosis is often observed in alcoholic Japanese men, in
      whom the prevalence of squamous cell dysplasia and carcinoma (SCC) in the upper
      aerodigestive tract are high. This study evaluated the associations of esophageal
      melanosis with these neoplasms, and the factors contributing to the development
      of esophageal melanosis in this population. METHODS: Endoscopic screening was
      combined with esophageal iodine staining in 1535 alcoholic Japanese men (aged 40
      79 years), of whom 1007 underwent aldehyde dehydrogenase-2 (ALDH2) genotyping.
      RESULTS: Fifty patients (3.3%) were diagnosed with esophageal melanosis, which
      had a higher incidence in those with noncancerous distinct iodine-unstained
      lesions (DIULs; 16/268; 6.0%), esophageal SCC (9/66; 13.6%), and
      oropharyngolaryngeal SCC (4/19; 21.1%) than in cancer- and DIUL-free controls
      (24/1182; 2.0%). The presence of esophageal melanosis was associated with higher
      risks for noncancerous DIULs, esophageal SCC, and oropharyngolaryngeal SCC (odds
      ratios, 2.81, 6.54, and 14.77, respectively). Men with the inactive ALDH2*1/2*2
      genotype had a higher risk for esophageal melanosis (2.66-fold), as well as for
      DIULs and SCCs. CONCLUSIONS: The presence of esophageal melanosis in alcoholic
      Japanese men could indicate a high risk for DIULs and SCCs in the upper
      aerodigestive tract. The high incidence of esophageal melanosis may be partially
      linked to high acetaldehyde exposure, a consequence of drinking alcohol in
      persons with inactive ALDH2.

PMID- 16082584
TI  - Effects of antisecretory agents on angiogenesis during healing of gastric ulcers.
AB  - BACKGROUND: We studied the effects of a proton pump inhibitor (PPI) and an H2
      receptor antagonist (H2-blocker) on angiogenesis during gastric ulcer healing, by
      examining stromal cell-derived factor (SDF-1) and CXC chemokine receptor 4
      (CXCR4) expression in the gastric mucosa. METHODS: Patients with gastric ulcers
      were allocated to an untreated control group, consisting of patients with active
      ulcers (GA), healing ulcers (GH), and ulcer scars (GS) or a PPI group (P; given
      rabeprazole at 20 mg/day), or an H2-blocker group (H; given nizatidine at 800
      mg/day). Frozen sections of biopsy specimens were examined by reverse
      transcription-polymerase chain reaction (RT-PCR) to analyze SDF-1 and CXCR4 mRNA.
      RESULTS: CXCR4 mRNA levels were elevated in the control (GH and GS patients)
      group and the H2-blocker group. CXCR4 was significantly elevated in the P-GA
      subgroup of the PPI group (P<0.01), but its level decreased with time.
      CONCLUSIONS: In the PPI group, CXCR4 levels were increased in the early phase of
      ulcer healing and returned to a level similar to that in the control group during
      the scar phase. These results suggest that PPIs increase the expression of CXCR4
      mRNA and thus promote vessel regeneration and maturation, facilitating ulcer
      healing.

PMID- 16082585
TI  - Elevated cyclooxygenase-2 expression in patients with early gastric cancer in the
      gastric pylorus.
AB  - BACKGROUND: Duodenogastric reflux after surgery increases the risk of gastric
      carcinoma. To determine whether bile reflux influences the development of gastric
      cancer in patients who have not had surgery, we compared cyclooxygenase-2 (COX-2)
      immunoreactivity in early gastric cancer originating from the gastric pylorus and
      that originating from other locations. We also examined the effects of bile acids
      on the expression and activity of COX-2 in gastric cells in vitro. METHODS: Tumor
      sections from 79 patients who underwent endoscopic mucosal resection for early
      intestinal-type gastric carcinoma were stained using a COX-2-specific monoclonal
      antibody. Immunoblotting of COX-2 was used to assess the effects of bile acids on
      COX-2 expression and activity in human gastric cell lines. RESULTS: Among the 79
      early gastric cancer lesions studied, 13 (16%) arose in the gastric pylorus. In
      this group, COX-2 immunoreactivity was negative to weak in 38% (5 of 13 lesions)
      and moderate to strong in 62% (8 of 13 lesions). In the control group, COX-2
      immunoreactivity was negative to weak in 70% (46 of 66 lesions) and moderate to
      strong in 30% (20 of 66 lesions). COX-2 expression was significantly elevated in
      early gastric cancer located in the gastric pylorus, compared with that in the
      other locations. In human gastric cell lines, bile acids induced COX-2
      expression, mediated by the ERK 1/2 mitogen-activated protein kinase pathway.
      CONCLUSIONS: COX-2 expression is elevated in early gastric cancer of the gastric
      pylorus, a common site of gastric cancer. Bile acids induced COX-2 expression in
      human gastric cell lines, suggesting a role of bile reflux in gastric
      carcinogenesis.

PMID- 16082586
TI  - Study for determination of the optimal cessation period of therapy with anti
      platelet agents prior to invasive endoscopic procedures.
AB  - BACKGROUND: Anti-platelet agents are widely used for the treatment and prevention
      of thrombotic diseases. On the other hand, continuation of anti-platelet agents
      increases the risk of hemorrhagic complications in gastrointestinal endoscopy,
      and cessation of anti-platelet agents exposes the patient to the risk of
      thromboembolism. Only a few studies have actually studied the whether a cessation
      period is required prior to endoscopic procedures and if so, the optional
      duration of the period. The present study assessed the time course of primary
      hemostasis after the cessation of anti-platelet agents. METHODS: Eleven healthy
      men (age range, 19-29 years) were assigned to each of the following regimens:
      aspirin (ASA; 100 mg/day), ticlopidine (TP; 300 mg/day), and a combination of ASA
      (100 mg/day) and TP (300 mg/day) for 7 days. There was a washout period of more
      than 3 weeks between each regimen. A quantitative bleeding time test (QBT test)
      and platelet aggregation test were performed before the beginning of
      administration, on the last day of administration, and at 1, 3, and 5 days after
      cessation, and also at 7 days after cessation for the combination regimen.
      RESULTS: The average bleeding time (BT) and total bleeding loss volume (Tv) of
      the 11 subjects after administration of the three regimens were significantly
      increased compared with those before administration. With the administration of
      ASA, increases of BT and Tv at 3 days after cessation were not significant. The
      Tv at 5 days after cessation of TP was not significantly increased. With the
      combination regimen, the BT and Tv at 7 days after cessation were not
      significantly increased. CONCLUSIONS: A 3-day cessation period for ASA, a 5-day
      cessation period for TP, and a 7-day cessation period for ASA+TP administration
      seem to be sufficient.

PMID- 16082587
TI  - Analysis of SMAD4/DPC4 gene alterations in multiploid colorectal carcinomas.
AB  - BACKGROUND: Although recent animal studies have shown that SMAD4/DPC4 gene
      alterations are essential for late-stage intestinal tumorigenesis, the role of
      SMAD4/DPC4 gene alterations in primary human colorectal carcinomas is not fully
      understood. Therefore, we attempted to clarify the role of the SMAD4/DPC4 gene
      during tumor progression of colorectal carcinoma. METHODS: Differences in allelic
      imbalance (AI) and mutations of the SMAD4/DPC4 gene between diploid and aneuploid
      populations were analyzed for 30 sporadic DNA multiploid colorectal carcinomas
      (used as a tumor progression model and defined as the coexistence of diploid and
      aneuploid cells within the same tumor). The crypt isolation technique was coupled
      with DNA cytometric sorting and a polymerase chain reaction assay. In addition,
      hypermethylation of the promoter region was examined to clarify whether
      inactivation of gene expression occurred. RESULTS: Although a SMAD4/DPC4 gene AI
      was detected in only 5 of 27 informative diploid populations, 25 of 27 aneuploid
      populations had a SMAD4/DPC4 gene AI. Mutation of the SMAD4/DPC4 gene was
      detected in only one aneuploid population of multiploid colorectal carcinomas,
      but not in the corresponding diploid population. In total, 20 available
      multiploid carcinomas were selected for methylation analysis, and no evidence of
      hypermethylation of the promoter region was found. CONCLUSIONS: We suggest that,
      although mutation of the SMAD4/DPC4 gene and hypermethylation of the promoter
      region are infrequent events in colorectal tumorigenesis, AI at the SMAD4/DPC4
      gene locus may play a key role in the progression of colorectal carcinomas.

PMID- 16082588
TI  - Expression of MAGE-A1 mRNA is associated with gene hypomethylation in
      hepatocarcinoma cell lines.
AB  - BACKGROUND: A correlation between melanoma-associated antigen (MAGE) A1 mRNA
      expression and genome-wide hypomethylation has been observed in some carcinomas,
      but this relationship is not known in hepatocarcinoma. METHODS: Total RNA and
      genomic DNA were prepared from ten human hepatocarcinoma cell lines in which the
      genetic characteristics are stable. MAGE-1 mRNA expression was determined by
      reverse transcription polymerase chain reaction (RT-PCR), and the level of genome
      wide demethylation was evaluated by enzyme digestion and Southern-blot assay. The
      methylation status of the MAGE-A1 gene promoter was measured by enzyme digestion
      and PCR. RESULTS: MAGE-A1 mRNA was detected in the hepatocarcinoma cell lines QGY
      7703, SMMC-7721, HLE, BEL-7402, BEL-7404, and BEL-7405, which showed moderate to
      low levels of cell differentiation. In contrast, MAGE-A1 mRNA expression was not
      detected in the hepatoma cell lines HepG2215, HepG2, QGY-7701, and Huh7, which
      showed moderate to high levels of differentiation. The level of demethylation in
      MAGE-A1 mRNA-positive cell lines was much higher than that in MAGE-A1 mRNA
      negative cell lines (P=0.02). CONCLUSIONS: The results suggest that MAGE-A1 mRNA
      expression in human hepatoma cell lines is associated with hypomethylation of the
      genome and the MAGE-A1 promoter domain. This study will be helpful to reveal the
      expression mechanisms of MAGE-like tumor antigens in cancer cells.

PMID- 16082589
TI  - Differential effects of interferon alpha-2b and beta on the signaling pathways in
      human liver cancer cells.
AB  - BACKGROUND: Interferon (IFN) has been reported to reduce the incidence of
      hepatocellular carcinoma (HCC) in patients with chronic hepatitis C and the
      recurrence of HCC after effective treatment. We examined the effect of IFNs on
      the proliferation and the signaling pathways of human HCC cells. METHODS:
      Cellular proliferation was examined by a modified 3-(4,5-dimethylthiazol-2-yl)
      2,5 diphenyltetrazolium bromide (MTT) assay. Activities of signaling molecules
      were evaluated by Western blot analysis. RESULTS: Cellular growth was not
      significantly modulated by IFNalpha-2b or by IFN-beta, even though the HCC cells
      expressed the IFN receptors. However, extracellular signal-regulated kinase
      (ERK)1/2 was activated by treatment with IFNalpha-2b, and both ERK1/2 and AKT
      were activated by treatment with IFN-beta, implying a possible role in resistance
      to IFNs. Contrary to our expectations, inhibition of mitogen-activated ERK
      regulating kinase (MEK) or phosphatidylinositol-3-OH kinase (PI3K) did not
      modulate the proliferation of HCC cells. Also, abrogation of the ERK1/2 and AKT
      signaling pathways did not affect cell-cycle arrest at the G1/S phase caused by
      IFNalpha-2b. CONCLUSIONS: IFNalpha-2b and IFN-beta activated ERK1/2 and/or AKT
      independently of modulating the proliferation of HCC cells and the cell-cycle
      machinery. A signal transduction-based approach for HCC treatment needs to focus
      on other possible signaling molecules besides ERK1/2 and AKT when challenged with
      IFNs.

PMID- 16082590
TI  - Different concentrations of various radiopharmaceuticals in the two main liver
      lobes: a preliminary study in clinical patients.
AB  - BACKGROUND: At clinical scintigraphic examinations of the abdomen using single
      photon emission computed tomography (SPECT), we have observed a different
      distribution between the left and right main liver lobes of various
      radiopharmaceuticals. This was studied retrospectively in clinical patients.
      METHODS: Examinations with [123I]-metaiodobenzylguanidine MIBG; (n=19), a 99mTc
      labelled monoclonal antibody against granulocytes (n=18), and 111In-pentetreotide
      (n=26) were assessed. There was no known history of, or risk factor for liver
      disease, and all lobes showed a uniform activity distribution. Twenty healthy
      volunteers underwent consecutive examinations with 99mTc-dimethyliminodiacetic
      acid (HIDA). The activity ratios between the left and right main liver lobes were
      calculated from the transverse tomographic (SPECT) sections. RESULTS: The left:
      right lobar activity ratio for [123I]-MIBG was (mean+/-SD) 1.25+/-0.21 (null
      hypothesis=1.00; P<0.001); for the antibody, acquisition after 3-5 h was 0.98+/
      0.06 (NS) and after 20-24 h, 0.99+/-0.11 (NS); for 111In-pentetreotide, 0.90+/
      0.09 (P<0.001); for 99mTc-HIDA, immediate acquisition, 0.68+/-0.12 (P<0.001) and
      acquisition at 7 min, 0.66+/-0.12 (P<0.001). CONCLUSIONS: The differences in
      tracer uptake between the liver lobes cannot be caused only by differences in
      blood flow. One explanation of the higher uptake of [123I]-MIBG by the left lobe
      may be a greater presence of catecholamines and a higher sympathetic nerve
      density in this liver portion. Consequently, there may be a functional difference
      between the two main liver lobes.

PMID- 16082591
TI  - CT evaluation of paraaortic lymph node metastasis in patients with biliary
      cancer.
AB  - BACKGROUND: The extent of paraaortic lymph node (PAN) metastasis parellels that
      of distant metastases in patients with biliary carcinoma. Accurate preoperative
      assessment of PAN metastasis has a crucial impact on surgical indications. In
      this retrospective study, we evaluated whether computed tomography (CT) scans
      were useful for diagnosing PAN metastases and excluding patients with PAN
      metastases from an indication for surgery. METHODS: Between March 1999 and
      November 2003, 57 patients with biliary carcinoma underwent radical
      lymphadenectomy or surgical biopsy of PANs. Nine of these patients were diagnosed
      as having PAN metastasis microscopically. All patients had undergone abdominal CT
      scans before surgery. To diagnose PAN metastases, we used the following
      diagnostic criteria. (1) Size; when lymph nodes were greater than 12 mm, 10 mm, 8
      mm, or 6 mm in longo or short-axis diameter, the nodes were considered
      metastatic. (2) Shape and size; when the axial ratio of a lymph node was greater
      than 0.5, 0.7, 1.0, and the maximum diameter of the long or short axis was
      greater than 12 mm, 10 mm, 8 mm, or 6 mm, the node was considered metastatic. (3)
      Internal structure; if the internal structure of a PAN was heterogeneous, the
      node was considered metastatic. A positive predictive value was calculated for
      each included criterion when patients numbered ten or more. RESULTS: Positive
      predictive values using the above criteria ranged from 13% to 36%. Only one
      patient had PANs with heterogeneous internal structures. CONCLUSIONS: We were
      unable to determine surgical indications based on the morphological criteria
      revealed by a CT scan.

PMID- 16082592
TI  - Mode of progression of intraductal papillary-mucinous tumor of the pancreas:
      analysis of patients with follow-up by EUS.
AB  - BACKGROUND: We investigated the mode of progression of intraductal papillary
      mucinous neoplasm of the pancreas (IPMN) in patients who underwent follow-up in
      order to elucidate the characteristics of malignancy and to establish an
      effective treatment strategy. METHODS: Fifty-one patients with IPMN (branch-duct
      type, 47; main-duct type, 4) who had undergone follow-up study by endoscopic
      ultrasonography (EUS) were included (mean follow-up duration, 41.0+/-32.3 months;
      average number of EUS examinations performed during follow-up, 4.4).
      Chronological changes in EUS findings and histological findings of resected
      specimens were evaluated. RESULTS: Of the patients with the branch-duct type,
      only 2% showed enlargement of the dilated branches. In the main-duct-type group,
      an increase in size of the main pancreatic duct (MPD) was observed in 75% of the
      patients. In 14 patients with papillary protrusions, an increase in size and
      lateral spread was observed in 71% and 43%, respectively. No patients developed
      invasive cancer. In 15 patients who had thick septum-like structures (TSS), the
      development of papillary protrusions and that of invasive cancer were observed in
      53% and 13%, respectively. Twenty-nine patients who had thin septum-like
      structures showed no change. Two patients with dense multilocular large cysts and
      TSS developed invasive cancer without change in the cystic lesions. One patient
      developed carcinoma with multifocal stromal invasion. CONCLUSIONS: Patients with
      branch-duct type IPMNs without papillary protrusions or TSS are not immediate
      candidates for surgery. Those who have small papillary protrusions have a benign
      course. It is recommended that patients with the large branch-duct type with TSS
      should undergo surgery. Attention should be paid to the entire pancreas when
      performing follow-up examinations in patients with branch-duct type IPMN, as
      invasive ductal adenocarcinoma can develop at a site in the pancreas different
      from that of the IPMN.

PMID- 16082593
TI  - Recovery from idiopathic thrombocytopenic purpura (ITP) following right
      hemicolectomy for mucocele of appendix.
AB  - A 61-year-old woman with a 2-year medication-free history of idiopathic
      thrombocytopenic purpura was referred to our hospital complaining of right lower
      abdominal pain. The platelet count was about 3-4x10(4)/mm3. This patient was
      diagnosed with mucocele of the appendix on computed tomography and colonoscopy.
      We performed only right hemicolectomy without splenectomy. The pathological
      diagnosis was mucinous cystadenoma of the appendix. The platelet count increased
      to 18.1x10(4)/mm3 on postoperative-day 7, and remained stable, at 20
      24x10(4)/mm3, for 14 months after the operation. Platelet-associated
      immunoglobulin G decreased remarkably after the operation, to 30.2 ng/10(7)
      cells, from 240 ng/10(7) cells preoperatively. We describe the first case of
      recovery from idiopathic thrombocytopenic purpura following right hemicolectomy
      performed for mucocele of the appendix. Considering our patients clinical course,
      it is possible that mucinous cystadenoma of the appendix may have influenced the
      thrombocytopenia. Findings in this patient suggest that mucocele of the appendix
      may be associated with a new diagnosis and idiopathic thrombocytopenic purpura
      treatment.

PMID- 16082594
TI  - Severe dysplasia of the gallbladder associated with occult pancreatobiliary
      reflux.
AB  - Pancreatobiliary reflux usually occurs in patients with pancreaticobiliary
      maljunction and can be associated with the occurrence of gallbladder carcinoma.
      We present the case of a patient with pancreatobiliary reflux despite having a
      normal pancreatobiliary junction (occult pancreatobiliary reflux; OPBR), in whom
      the resected gallbladder presented severe dysplasia. The patient, a 61-year-old
      woman, showed thickness of the gallbladder wall, detected by ultrasonography and
      computed temography (CT). Her biliary amylase level in the common bile duct was
      103,000 IU/l, and in the gallbladder it was 153,500 IU/l, although endoscopic
      retrograde cholangiopancreatography revealed a normal pancreaticobiliary
      junction. Immunohistochemical staining showed many p53-positive nuclei in the
      dysplastic lesion, and about 50% of the dysplastic cells exhibited diffuse
      nuclear staining for Ki-67. In the present patient, early diagnosis of occult
      pancreatobiliary reflux led to early detection of a precancerous lesion of the
      gallbladder mucosa.

PMID- 16082595
TI  - Corticosteroid-responsive pancreatic cyst found in autoimmune pancreatitis.
AB  - There have been only a few reports of autoimmune pancreatitis complicated with
      pancreatic cyst and such cysts are rare, probably due to the absence of severe
      tissue necrosis and/or lack of stasis of the pancreatic juice in this condition.
      However, during a follow-up of 48 patients with this disease, we found 3 patients
      with pancreatic cysts, and this enabled us to evaluate their clinicopathological
      findings. Between September 1994 and July 2003, we treated and followed 48
      patients with autoimmune pancreatitis, and found 3 patients with pancreatic cyst
      formation that was responsive to corticosteroid therapy. All of the patients with
      cysts had high serum IgG4 concentrations. After corticosteroid therapy, rapid
      resolution of the pancreatic cysts was observed. Immunostaining with goat
      polyclonal antibody for each IgG subclass showed severe infiltration of IgG4
      positive plasma cells in the cyst wall in one patient. The high serum IgG4
      concentration and favorable response to corticosteroid therapy suggests that a
      highly active state of the inflammatory process is closely associated with cyst
      formation, and that a corticosteroid-responsive pancreatic cyst is a
      characteristic feature of autoimmune pancreatitis.

PMID- 16082596
TI  - Culture-proven small intestinal bacterial overgrowth as a cause of irritable
      bowel syndrome: response to lactulose but not broadspectrum antibiotics.

PMID- 16082597
TI  - A case report of chronic enterocolic phlebosclerosis; a possible consequence of
      chronic manifestation of enterocolic phlebitis.

PMID- 16082598
TI  - Hepatic sarcoidosis found as a small liver SOL in a patient with type C
      cirrhosis.

PMID- 16082599
TI  - Haploinsufficiency in multiploid colorectal cancer.

PMID- 16082600
TI  - Treatment strategy of intraductal papillary-mucinous tumor of the pancreas.

PMID- 16082601
TI  - Safety of abciximab administration during PCI of patients with previous stroke.
AB  - OBJECTIVES: To examine the frequency of cerebrovascular complications among
      patients receiving abciximab (AB) undergoing PCI with prior intracranial
      hemorrhage (ICH) or recent (< 2 years) ischemic strokes. BACKGROUND: AB improves
      clinical outcomes in high-risk patients undergoing percutaneous coronary
      intervention (PCI); however, the safety of AB in patients with prior stroke has
      not been adequately studied. METHODS: A database review of 7,244 consecutive
      PCIs, from 7/97 to 10/01, identified 6,190 PCIs performed with AB among which 515
      interventions were performed in patients with prior stroke history [ICH or recent
      ischemic stroke, (n = 101) and remote (> 2 years) ischemic stroke, (n = 414)].
      RESULTS: The post-PCI stroke rate was significantly higher in patients with prior
      stroke (2.06% vs. 0.35%, p < 0.001 for all stroke; 0.38% vs. 0.03%, p = 0.023 for
      ICH). The incidence of ICH among the AB-treated group was 0.065%; a history of
      prior stroke did not increase the incidence of ICH in the AB-treated group (0.39%
      vs. 0.0%, p = ns). Moreover, the post-PCI stroke rate was similar between the
      prior ICH or recent ischemic stroke-group and remote ischemic stroke-group (2 vs.
      1.9%; OR: 1.03; 95% CI: 0.21-4.90; p = ns for all strokes; 2% vs. 1.5%; OR: 1.4;
      95% CI: 0.27-6.91; p = ns for ischemic stroke). Importantly, no ICH occurred in
      patients with recent ischemic or any prior ICH stroke. CONCLUSIONS: Abciximab, in
      addition to aspirin, heparin and ADP-inhibitors does not increase the risk of
      stroke in patients with prior stroke undergoing PCI.

PMID- 16082602
TI  - The role of gender and other factors as predictors of not receiving reperfusion
      therapy and of outcome in ST-segment elevation myocardial infarction.
AB  - BACKGROUND: The standard of care for ST-segment elevation myocardial infarction
      (STEMI) is prompt coronary reperfusion with thrombolysis or percutaneous coronary
      intervention. Women have higher mortality rates than men following STEMI and
      fewer women are considered eligible for reperfusion therapy. We analyzed the
      impact of gender, and other factors, on the outcome and treatment of STEMI in the
      TETAMI trial and registry. METHODS: This exploratory analysis included 2741
      patients from Treatment with Enoxaparin and Tirofiban in Acute Myocardial
      Infarction (TETAMI) presenting with STEMI within 24 hours of symptom onset. The
      primary composite end point was the combined incidence of all-cause death,
      recurrent myocardial infarction, and recurrent angina, at 30 days. Three
      multivariate analyses were performed to determine predictors of not receiving
      reperfusion therapy, the composite end point, or death. RESULTS: The triple end
      point occurred in 17.8% of women versus 13.3% of men. Reperfusion therapy was
      utilized in 38.2% of women versus 47.3% in men. However, age > 75 years, delayed
      presentation, high systolic blood pressure (> 100) and region (South Africa),
      were significant, independent predictors of not receiving reperfusion therapy.
      Significant predictors of the triple end point included not receiving reperfusion
      therapy, age > 60 years, and higher Killip class. Predictors of death included
      age > 60 years, low systolic blood pressure, higher Killip class, high heart
      rate, delayed presentation, and region (South Africa and South America).
      CONCLUSION: Female gender was not an independent predictor of outcome or
      underutilization of reperfusion therapy. Factors more common in female STEMI
      patients (advanced age and delayed presentation) were associated with not
      receiving reperfusion therapy and adverse outcome. Increased awareness is needed
      to reduce delayed presentation after symptom onset, especially among women.
      Abbreviated abstract. In this analysis of 2741 ST-segment elevation myocardial
      infarction patients in the TETAMI trial and registry, a trend was observed for
      women being less likely to receive reperfusion therapy and more likely to have an
      adverse outcome than men. This was related to factors more common in female
      patients (advanced age and delayed presentation), and showed that an increased
      awareness is needed to reduce delayed presentation after symptom onset,
      especially among women.

PMID- 16082603
TI  - The impact of patient self-testing of prothrombin time for managing
      anticoagulation: rationale and design of VA Cooperative Study #481--the Home INR
      Study (THINRS).
AB  - BACKGROUND: Anticoagulation (AC) with warfarin reduces the risk of
      thromboembolism (TE) in a variety of applications, yet despite compelling
      evidence of the value and importance of high quality AC, warfarin remains
      underused, and dosing is often suboptimal. Approaches to improve AC quality
      include (1) an AC service (ACS), which allows the physician to delegate day-to
      day details of AC management to another provider dedicated to AC care, and (2)
      incorporating into the treatment plan patient self-testing (PST) under which,
      after completing a training program, patients perform their own blood testing
      (typically, using a finger-stick blood analyzer), have dosage adjustments guided
      by a standard protocol, and forward test results, dosing and other information to
      the provider. Studies have suggested that PST can improve the quality of AC and
      perhaps lower TE and bleed rates. The purpose of Department of Veterans Affairs
      (VA) Cooperative Studies Program (CSP) #481, "The Home INR Study" (THINRS) is to
      compare AC management with frequent PST using a home monitoring device to high
      quality AC management (HQACM) implemented by an ACS with conventional monitoring
      of prothrombin time by international normalized ratio (INR) on major health
      outcomes. PST in THINRS involves use of an INR monitoring device that is FDA
      approved for home use. STUDY DESIGN: Sites are VA Medical Centers where the ACS
      has an active roster of more than 400 patients. THINRS includes patients with
      atrial fibrillation (AF) and/or mechanical heart valve (MHV) expected to be
      anticoagulated indefinitely. THINRS has two parts. In Part 1, candidates for PST
      are evaluated for 2 to 4 weeks for their ability to use home monitoring devices.
      In Part 2, individuals capable of performing PST are randomized to (1) HQACM with
      testing every 4 weeks and as indicated for out of range values,
      medication/clinical changes, or (2) PST with testing every week and as indicated
      for out of range values, medication/clinical changes. The primary outcome measure
      is event rates, defined as the percent of patients who have a stroke, major
      bleed, or die. Secondary outcomes include total time in range (TTR), other events
      (myocardial infarction (MI), non-stroke TE, minor bleeds), competence and
      compliance with PST, satisfaction with AC, AC associated quality of life (QOL),
      and cost-effectiveness. To assess the effect of PST frequency on TTR and other
      outcomes, at selected sites patients randomized to perform PST are assigned one
      of three test frequencies (weekly, twice weekly, or once every four weeks).

PMID- 16082604
TI  - Once-daily enoxaparin in the outpatient setting versus unfractionated heparin in
      hospital for the treatment of symptomatic deep-vein thrombosis.
AB  - BACKGROUND: Once- and twice-daily low-molecular-weight heparin administered in
      hospital have been shown to be effective and safe for treating deep-vein
      thrombosis. The aim of this study was to compare the efficacy and safety of deep
      vein thrombosis treatment using once-daily subcutaneous enoxaparin in the
      outpatient setting with intravenous unfractionated heparin in hospital. METHODS:
      This randomized, parallel-group, open-label study was conducted in 18 centers in
      4 countries. In total, 298 patients with symptomatic deep-vein thrombosis who
      were eligible for home treatment were randomized to treatment with enoxaparin in
      the outpatient setting (1.5 mg/kg subcutaneously once-daily) or unfractionated
      heparin in hospital (5000 IU bolus and 1250 IU/hour intravenous infusion) for >
      or =5 days. Clinical endpoints were assessed during a 6-month follow-up period.
      RESULTS: Among all patients treated with enoxaparin, there was a trend towards
      fewer recurrent deep-vein thromboses (1.3% vs. 5.4%; p = 0.060) and pulmonary
      emboli (1.3% vs. 4.1%; p = 0.17) compared with patients treated with
      unfractionated heparin. When considering a post-hoc combined endpoint of deep
      vein thrombosis and pulmonary embolism, significantly fewer events occurred in
      the enoxaparin group than in the unfractionated-heparin group (2.7% vs. 8.8%; p =
      0.026). The incidences of bleeding events and adverse events in the enoxaparin
      and unfractionated-heparin groups were similar. CONCLUSIONS: Once-daily
      subcutaneous enoxaparin in the outpatient setting is at least as effective and as
      well tolerated as in-hospital intravenous unfractionated heparin for treatment of
      deep-vein thrombosis.

PMID- 16082605
TI  - Transitioning from argatroban to warfarin in heparin-induced thrombocytopenia: an
      analysis of outcomes in patients with elevated international normalized ratio
      (INR).
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) can lead to catastrophic
      thromboembolic complications and requires treatment with an alternative, rapidly
      active anticoagulant, such as a direct thrombin inhibitor (DTI), either to
      prevent or treat these complications. Switching to oral warfarin after initial
      treatment with a DTI is necessary in most patients. Most references related to
      warfarin suggest that an increased risk for bleeding will occur with elevated
      international normalized ratios (INRs) > 4.6. In patients receiving argatroban,
      it is not uncommon to achieve an INR > 4 during this transition. Because the
      clinical outcomes in patients achieving an INR > 4 during combined
      argatroban/warfarin therapies for HIT are not well described, we evaluated the
      clinical outcomes of 111 patients with this phenomenon. METHODS: We identified
      patients from the prospective studies of argatroban anticoagulation, Argatroban
      911 and Argatroban-915. Data collected from these studies included death from all
      causes, amputation, new thrombosis, major bleeding, INR values, argatroban doses,
      aPTT values, platelet counts, and duration of therapy. RESULTS: Patients were on
      argatroban monotherapy for a median of 2.8 (0.1-8.1) days, and on cotherapy for a
      median of 3.7 (0.9-12.8) days. The median platelet count was 70.9 (18-325) x
      10(9)/L at the time of HIT diagnosis and increased to 94 (30-324) x 10(9)/L by
      the time warfarin was initiated. At a median argatroban dose of 1.4 (0.2-2.0)
      mcg/kg/min, the maximum INR ranged from 4.1 to 21.2 (median 6.4, n = 111) and the
      corresponding aPTT ranged from 48.1 to 105 (median 71, n = 93) seconds. After
      argatroban cessation, the first recorded INR within 4 to 24 hours ranged from 1.5
      to 12.5 (median 2.9, n = 58). Adverse clinical outcomes occurred in 9 (8.1%)
      patients during cotherapy and in 12 (10.8%) patients after argatroban
      anticoagulation was discontinued. Adverse clinical outcomes included 7 cases of
      new thrombosis, 3 amputations, 12 deaths and 1 major bleed. Eleven of 12 (91.7%)
      patients died due to causes other than thrombosis, and most deaths (83%) occurred
      following cotherapy. Five (4.5%) patients developed new thrombosis during
      argatroban/warfarin cotherapy despite an INR > 4. In contrast only 1 (0.9%)
      patient experienced major bleeding. CONCLUSION: In patients receiving
      argatroban/warfarin cotherapy and with an elevated INR > 4, the risk for
      thrombosis exceeds the risk of bleeding. Traditional paradigms concerning
      elevated INRs and warfarin may need to be redesigned for the patient population
      on cotherapy with direct thrombin inhibitors.Abbreviated Abstract. The clinical
      outcomes of 111 patients with INRs > 4 while on combined argatroban (dose < or =
      2 mcg/kg/min) and warfarin were evaluated. Adverse clinical outcomes (7 new
      thrombosis, 3 amputations, 12 deaths and 1 major bleed) occurred in 21 patients.
      Eleven deaths were due to causes other than thrombosis. Five patients developed
      new thrombosis while only 1 had major bleeding. The risk for thrombosis exceeds
      the risk of bleeding in patients with HIT despite an INR > 4.

PMID- 16082606
TI  - A case control study on the contribution of factor V-Leiden, prothrombin G20210A,
      and MTHFR C677T mutations to the genetic susceptibility of deep venous
      thrombosis.
AB  - BACKGROUND: Insofar as the inherited prothrombotic single nucleotide
      polymorphisms (SNPs) factor V G1691A (FV-Leiden), prothrombin (PRT) G20210A, and
      methylenetetrahydrofolate reductase (MTHFR), C677T are inherited risk factors of
      venous thromboembolism (VTE), the aim of this study was to determine the
      prevalence of single and combined SNPs in 198 patients with documented deep
      venous thrombosis (DVT), and 697 control subjects, and to estimate the associated
      risks. METHODS: Factor V-Leiden, PRT G20210A, and MTHFR C677T were analyzed by
      PCR and restriction fragment length polymorphism (RFLP). RESULTS: The prevalence
      of the heterozygote and homozygous variants for FV-Leiden (52.02 vs. 14.78%, RR
      6.28), PRT G20210A (19.2 vs. 3.6%; RR 6.38), and to a lesser extent the T/T
      genotype of MTHFR C677T (20.71 vs. 11.0%; RR 1.49) were higher among DVT patients
      vs. controls, respectively. Two or more SNPs were detected in 90 of 198 patients
      (45.5%) and in 60 of 697 controls (8.6%), with odds ratios of 16.754 for joint
      occurrence of FV-Leiden and PRT G20210A, 10.471 for FV-Leiden and MTHFR C677T,
      and 6.283 for PRT G20210A SNPs and MTHFR 677T/T. Logistic regression analysis
      showed a further increased odds for FV-Leiden in combination with PRT G20210A
      (85.198) or homozygous MTHFR C677T (81.133), and to a lesser extent for PRT
      G20210A in combination with homozygous MTHFR C677T (20.812). CONCLUSIONS: This
      indicates that FV-Leiden and PRT G20210A, more than MTHFR C677T, are important
      risk factors for DVT, and that the presence of more than one prothrombotic SNPs
      was associated with a significant risk of DVT.

PMID- 16082607
TI  - Mini-dose pump-prime aprotinin inhibited enhanced fibrinolytic activity and
      reduced blood loss and transfusion requirements after coronary artery bypass
      surgery.
AB  - OBJECTIVES: Low-dose aprotinin in the pump during cardiopulmonary bypass (CPB)
      has been shown to improve postoperative hemostasis and platelet preservation.
      This investigation was undertaken to evaluate the effects of mini-dose pump prime
      only aprotinin (70 mg) on the hemostatic parameters and blood transfusion
      requirements in patients undergoing on-pump coronary artery bypass surgery
      (CABG). MATERIALS AND METHODS: We studied 86 patients who underwent CABG. Forty
      patients received mini-dose aprotinin (500.000 KIU [70 mg] in the pump), and a
      control group of 46 did not. D-dimer level, full blood count, postoperative blood
      loss, and transfusion requirements were analyzed before, after one hour operation
      and first day after operation. RESULTS: Twenty-four-hour postoperative blood loss
      was significantly reduced in the aprotinin group (188+/- 51.5 ml vs. 818+/- 243.5
      ml, [mean +/- standard deviation] p < 0.01). Patients in the aprotinin group also
      received significantly less banked blood posoperatively than the control group
      (1.20 +/- 0.52 vs. 3.33 +/- 1.13 Units/per patient (p < 0.04). One hour after
      operation, and 24 hours after operation D-dimer level was significantly reduced
      in the aprotinin group (p < 0.008 and p < 0.017, respectively). CONCLUSIONS: Mini
      dose pump-prime aprotinin reduces postoperative blood loss, transfusion
      requirements and yet confers hemostatic improvement through reduced fibrinolysis
      in patients undergoing routine coronary artery bypass grafting.

PMID- 16082608
TI  - Comparison of neutron activated and radiolabeled microsphere methods for
      measurement of transmural myocardial blood flow in dogs.
AB  - BACKGROUND: The 'gold standard' radioactive microsphere (RM) technique for
      measurement of organ blood flow under various experimental conditions is
      inaccessible to many researchers due to increasing environmental concerns
      regarding safety and disposal of low-level radioactive waste materials. A new
      method using neutron activated microspheres (NAM) has recently been described.
      METHODS: We compared regional myocardial blood flows using the new formulation
      STERIspheres (NAM; 15.0 +/- 0.1 [SD] microm; density 1.5 gr/mL) with RM (15.0 +/-
      0.1 [SD] microm; density 1.5 gr/mL) under different experimental conditions
      during acute ischemia-reperfusion injury in dogs. Random paired combinations of
      four different RM and NAM were co-injected into the left atrium during
      autoregulation, coronary occlusion and flow-mediated hyperemia (reperfusion) in
      the same animal. The left ventricle was divided into non-ischemic and ischemic
      regions and further subdivided into endocardial, mid-myocardial and epicardial
      portions. After gamma-counting, blood and myocardial tissue samples (n = 180)
      were dried and then shipped to a core facility for neutron activation and
      analysis. NAM-RM blood flow data were directly compared by ANOVA and regression
      analysis; Bland and Altman analysis was also performed to assess mean differences
      in blood flow with NAM-RM. RESULTS: A direct relation for blood flow between NAM
      RM was observed; the slope of the relation (1.17 RM +/- 0.04 [SEE]) was different
      from unity but the intercept (0.06 +/- 0.06 [SEE]) was not different from the
      origin. Intermethod mean differences were minimal between NAM-RM in the low to
      normal range of blood flow and were increased at the higher blood flow levels the
      latter being of minor physiological consequence. A direct relation for
      endo/epicardial blood flow ratios between NAM-RM was also observed; the slope of
      the relation (0.98 RM +/- 0.04 [SEE]) and the intercept (0.03 +/- 0.06 [SEE])
      were not different from unity or the origin, respectively. CONCLUSIONS: RESULTS
      show that in addition to limiting production of radioactive waste materials, NAM
      accurately measure myocardial blood flow, endocardial/epicardial and ischemic/non
      ischemic blood flow distributions over a wide range. We compared myocardial blood
      flows using paired combinations of neutron activated (NAM) and the 'gold
      standard' radiolabeled microspheres (RM) co-injected during autoregulation,
      coronary occlusion and flow-mediated hyperemia in an in situ canine ischemia
      reperfusion preparation. A direct relation for blood flow and endo/epicardial
      blood flow ratios between NAM-RM was observed; intermethod mean differences
      between NAM-RM were minimal in the low to normal blood flow range but increased
      at higher blood flow levels. These results indicate that NAM accurately measure
      myocardial blood flow and its transmural distribution in addition to limiting
      unnecessary production of radioactive laboratory waste products.

PMID- 16082609
TI  - An examination of the association between therapeutic anticoagulation control and
      glycemic control for patients with diabetes on oral anticoagulation therapy.
AB  - BACKGROUND: Observations by pharmacists monitoring anticoagulated patients
      suggested that patients with diabetes often require more frequent international
      normalized ratio (INR) monitoring than patients without diabetes. The purpose of
      this investigation was to examine the association between glycemic control and
      therapeutic anticoagulation control. METHODS: Patients with diabetes who were
      receiving warfarin therapy monitored by the Kaiser Permanente of Colorado
      Clinical Pharmacy Anticoagulation Service were eligible for inclusion. Patients
      were included if they had a diagnosis of diabetes mellitus type 1 or 2, aged > or
      =18 years, and had initiated anticoagulant therapy > or =120 days before their
      most recent hemoglobin A1C measurement. The primary outcome was the correlation
      between hemoglobin A1C value and percent of time in the patient-specific INR
      range. Multivariate analysis was undertaken to regress percent of time in INR
      range on an A1C value > or =8.0 while adjusting for other possible explanatory
      variables. RESULTS: A total of 911 patients with diabetes were included in the
      study. Subjects with an A1C value > or =8.0 had similar characteristics as those
      subjects with an A1C value < 8.0. Correlation analysis revealed no relationship
      between percent of time spent in INR range and A1C value (Spearman Correlation
      Coefficient = 0.012, p = 0.805). Multivariate analysis revealed no relationship
      between percent of time spent in INR range and A1C value > or =8.0 (Odds Ratio =
      1.00; 95% Confidence Interval = 0.99, 1.01) when adjusting for possible
      explanatory variables. CONCLUSIONS: For patients with diabetes on warfarin
      anticoagulation therapy, there is no association between glycemic control and
      therapeutic anticoagulation control. However, anticoagulation therapy providers
      should manage these patients with the same diligence and care as patients without
      diabetes.

PMID- 16082610
TI  - Use of recombinant activated factor VII in an elderly female undergoing
      acenocoumarol thromboprophylaxis requiring an emergency laparotomy.

PMID- 16082611
TI  - Patient-specific antithrombotic strategies: lessons not yet learned from the
      renal insufficiency paradigm.

PMID- 16082612
TI  - Preferred temperature correlates with evaporative water loss in hylid frogs from
      northern Australia.
AB  - We measured temperature preferences of 12 species of hylid frogs (Litoria and
      Cyclorana) from northern Australia in a laboratory thermal gradient. These
      species represented a range of ecological habitat use (aquatic, terrestrial,
      arboreal), adult body size (0.5-60 g), and cutaneous resistance to water loss
      (Rc=0.6-63.1 s cm-1). We found significant differences among species in selected
      skin temperature and gradient temperature but not in the variances of these
      measures (an index of precision of temperature selection). The species'
      differences correlated significantly with cutaneous resistance to water loss,
      with more-resistant frogs selecting higher skin and substrate temperatures in the
      thermal gradient, even after phylogenetic relationships are taken into account.
      Because cutaneous resistance to water loss also correlates with ecological habit
      (arboreal>terrestrial>aquatic), we suggest that their higher resistance to water
      loss allows arboreal and terrestrial species better ability to tolerate high
      temperatures, where growth or locomotory speed may be higher, without the
      associated risk of desiccation.

PMID- 16082613
TI  - Ultraviolet light and visual behaviour in the three-spined stickleback,
      Gasterosteus aculeatus.
AB  - The ability of various vertebrates to perceive visual information in the
      ultraviolet region of the electromagnetic spectrum (300-400 nm) is receiving
      increasing interest. To date, many of these studies have concentrated on the role
      of ultraviolet perception in mate choice, yet there are several ways in which the
      ability to perceive ultraviolet information may affect other behaviours. Until
      now, it has been widely assumed that colour in the three-spined stickleback can
      be quantified by methods appropriate to the human visual system. However,
      evidence does exist that suggests that, in some populations, sticklebacks are
      capable of perceiving ultraviolet wavelengths. Using a behavioural technique, we
      tested the ability of the stickleback to perceive ultraviolet light under full
      spectrum conditions to establish whether such wavelengths are utilised within
      their normal behavioural repertoire. We tested this ability by assessing whether
      subjects could locate hidden food in a foraging task where food position was
      indicated by the position of landmarks. These landmarks differed only in their
      ultraviolet content, appearing identical when viewed across the human visible
      region of the spectrum. We found that sticklebacks were able to use ultraviolet
      perception to locate a foraging patch under full-spectrum conditions.

PMID- 16082614
TI  - [Factors associated with short- and long-term use of benzodiazepines in the
      elderly from Quebec].
AB  - In Quebec, benzodiazepines are some of the most extensively used drugs by the
      elderly. The goal of this study was to identify factors associated with short-
      and long-term benzodiazepine use among 2,039 elderly persons having participated
      in the Quebec Health Survey conducted in 1998. Results of the multivariate,
      multinomial logistic regression showed that a higher number of chronic health
      problems, a higher number of physicians visited and general practitioners
      consulted were associated with short- and long-term use of benzodiazepines.
      Factors specifically associated with long-term use were female gender (OR = 1.84)
      and the presence of benzodiazepine users in the household (OR = 1.90). In this
      study, we were unable to show a difference between the two groups of users with
      regards to the risk factors studied. This result leads us to conclude that
      prevention of long-term use must be aimed at all new benzodiazepine users.

PMID- 16082615
TI  - Evaluation of the restorative care education and training program for nursing
      homes.
AB  - Restorative care attempts to break the cycle of dependency and functional decline
      in nursing homes by addressing individual resident needs. The Restorative Care
      Education and Training (RCET) Program consists of a five-week workshop and
      resource manual for both supervisory and direct care staff. This paper describes
      the RCET approach and presents the implementation, process, and quasi
      experimental outcome evaluation findings with 42 residents from six intervention
      sites and six ''wait-list'' facilities who received usual care. Baseline data
      supported the fact that staff primarily targeted residents with substantial
      functional impairments. Over four months, residents who received restorative care
      improved significantly on several functional outcome indicators, while the
      comparison sample declined in several areas of functioning. Interviews with
      facility directors and participating staff provided direction for modifying the
      RCET and insight regarding opportunities and challenges when implementing
      restorative care activities in nursing homes.

PMID- 16082616
TI  - Unit manager's role with family members of clients in complex continuing care
      settings: An untold story.
AB  - Most literature on staff-family relationships has come from studies of long-term
      care settings, has focused mainly on the families' perspectives on factors
      affecting their relationships with staff, and has included scant findings from
      the staff's perspective. No studies that examined staff-family relationships in
      complex continuing care (CCC) environments from the perspective of staff were
      found in the literature. A qualitative study that draws on a grounded theory
      approach was conducted to explore staff-family relationships in CCC, and the
      findings presented in this article illuminate the unit manager's role. Data were
      collected through in-depth interviews with nine unit managers and a follow-up
      focus group with five unit managers who work in three CCC facilities. Three
      categories reflecting the unit manager's role with family members of clients in
      CCC settings were derived: establishing supportive entry; building and preserving
      relationships; and closing the loop. Implications of the findings for practice
      and future research are presented.

PMID- 16082617
TI  - Care-receiver and caregiver assessments of functioning: Are there gender
      differences?
AB  - In situations where care-receivers cannot respond to questions about their
      functional status, caregiver proxies are often substituted. Yet studies
      addressing caregiver-care-receiver agreement remain limited in scope, focusing
      primarily on cognitive functioning and caregiver relationship. This study
      broadens the range of research in this area by examining caregiver and care
      receiver reports of individual IADL and AADL items by gender of care-receiver. As
      well, the degree to which the care-receiver's age and mental and physical health
      status influence agreement are investigated. Data for this study come from a
      sample of 388 Manitoba older adults aged 65 and over. Results (using Cohen's
      kappa) suggest less agreement on the presence of disability for men than for
      women, particularly among those aged 75-84. Differences by health status were
      also revealed. The implications of the findings for assessments of functioning
      are considered.

PMID- 16082618
TI  - Understanding barriers to continence care in institutions.
AB  - This work seeks to identify factors that facilitate or diminish care-providers'
      propensity to improve continence care in long-term care (LTC) settings. We
      conducted a cross-sectional qualitative study using focus group methodology in
      four long-term care institutions in Montreal, QC. Forty-two nurses, nursing
      assistants, and orderlies caring for incontinent elderly residents were asked how
      they perceived urinary incontinence (UI), how it was being managed, and what
      factors enabled or hindered continence care in their institution. Content
      analysis was used. Facilitating and inhibiting elements of three
      individual/internal factors (beliefs about UI, attitudes towards the elderly, and
      knowledge about UI) and five institutional/external factors (workload demands,
      type of patient, environmental support, co-worker support, and attributes of UI
      interventions) emerged as important determinants of care-providers' propensity to
      manage UI. To be successful, continence programs must target multidimensional
      elements that take into account personal, systems, and organizational level
      factors.

PMID- 16082619
TI  - Dimensions of grandparent-adult grandchild relationships: From family ties to
      intergenerational friendships.
AB  - This paper examines the growing demographic phenomenon of grandparent-adult
      grandchild relationships from the perspectives of both generations. Drawing on
      qualitative life-history interviews (n = 37), this research explores the
      subjective meanings of the relationship, as well as the experiences of being
      grandparents and adult grandchildren. Despite tremendous diversity in grandparent
      adult grandchild relationships, including differences among and between
      generations, both groups in this study view one another positively and
      conceptualize their ties as personally and existentially meaningful. They
      classify their relationships as a distinct family tie centred on unconditional
      love, mutual support, respect, and obligation. A number of individuals also
      discuss their grandparent-adult grandchild relationships as friendships,
      involving mutual trust, shared confidences, and personal choice. Overall, this
      research suggests that grandparent-grandchild relationships often grow more
      profound and meaningful as grandparents and grandchildren age, move through the
      life course, and experience life events.

PMID- 16082620
TI  - A comparison of the behavioural and emotional characteristics of Alzheimer's
      dementia in individuals with and without Down syndrome.
AB  - The behavioural and emotional changes associated with Alzheimer's disease (AD)
      are compared for individuals with Down syndrome and AD and individuals with AD
      from the general population (AD-only). The primary caregivers of 30 people with
      Down syndrome and AD and 30 people with AD-only completed the BEHAVE-AD and the
      Apathy subscale of the CERAD. As well, behavioural observations at adult day
      programs were undertaken with selected participants (n = 26). The Down syndrome
      group experienced fewer delusions and had lower total scores on the BEHAVE-AD,
      indicating fewer problem behaviours overall. Day program observations suggested
      that the AD-only group were more likely to be sedentary and observe the
      activities of others, while the Down syndrome group were more physically active.
      Improving our understanding of the similarities and differences between these two
      groups may help facilitate the integration of individuals with Down syndrome into
      adult day programs for the general population.

PMID- 16082621
TI  - Wheelchair use among community-dwelling older adults: Prevalence and risk factors
      in a national sample.
AB  - Older adults are the largest group of wheelchair users yet there are no peer
      reviewed studies on the national profile of older wheelchair users in Canada. We
      investigated the characteristics of wheelchair users in a national sample of
      community-dwelling older adults from the Canadian Study of Health and Aging (CSHA
      2). Questions on the use of assistive technology were asked of 5395 Canadians
      (over 64), and 4.6 per cent reported using a wheelchair. Logistic regression was
      used to model the factors associated with wheelchair use. Controlling for age,
      gender, and cognitive impairment, older adults who reported greater dependence in
      basic self-care and instrumental activities of daily living were more likely to
      use a wheelchair. However, the effects of self-care dependence on wheelchair use
      varied by gender, with men more likely than women to use wheelchairs with
      increasing self-care dependence. The number of chronic health conditions and
      being unmarried also increased the odds of wheelchair use. This paper quantifies
      the risk of wheelchair use according to critical factors that can be used to
      project use and plan for services.

PMID- 16082622
TI  - Controlling drug release from imprinted hydrogels by modifying the
      characteristics of the imprinted cavities.
AB  - The aim of this study was to analyse the influence of the template/functional
      monomer proportion on the achievement of molecularly imprinted hydrogels with
      cavities with a high enough affinity for the drug to sustain drug release.
      Imprinted hydrogels were prepared from N,N-dimethylacrylamide and
      tris(trimethylsiloxy)sililpropyl methacrylate (DMAA and TRIS; main components),
      methacrylic acid (MAA; functional monomer), ethylene glycol dimethacrylate
      (EGDMA; cross-linker), and timolol (template drug). Photo-polymerization of the
      monomer solutions was carried out in poly(propylene) molds (0.3 mm thickness) to
      obtain contact lens-like devices. Non-imprinted control hydrogels were also
      prepared in the same way but without the addition of timolol. The imprinted
      hydrogels showed a higher affinity for timolol and a slower release rate than the
      non-imprinted hydrogels. The release rate decreased by increasing the MAA/timolol
      ratio in the gel recipe. Hydrogels prepared with 400 x 10(-3) M MAA, 600 x 10(-3)
      M EGDMA, and a timolol/MAA mole ratio of 1:16-1:32 had drug diffusion
      coefficients two orders of magnitude below those of non-imprinted hydrogels. The
      results obtained clearly indicate that the timolol release rate is critically
      affected by the conditions under which the hydrogels were synthesized. These
      effects are discussed on the basis of the influence of drug proportion on the
      conformation of the imprinted cavities.

PMID- 16082623
TI  - Genotype-phenotype relationships in an investigation of the role of proteases in
      abdominal aortic aneurysm expansion.
AB  - BACKGROUND: The aim of the study was to investigate the effect of functional
      polymorphisms in promoters of matrix metalloproteinase (MMP) 2, MMP-3, MMP-9, MMP
      12 and plasminogen activator inhibitor (PAI) 1 genes on the growth rate of small
      abdominal aortic aneurysms (AAA). METHODS: Some 455 individuals with a small AAA
      (4.0-5.5 cm) were monitored for aneurysm growth by ultrasonography (mean follow
      up 2.6 years). They also provided a DNA sample for analysis of the -1306 C > T, 
      1171 5A > 6A, -1562 C > T, -82 A > G and -675 4G > 5G alleles of MMP-2, MMP-3,
      MMP-9, MMP-12 and PAI-1, respectively. Mean linear AAA growth rates were
      calculated by flexible modelling; the sample size was sufficient to detect
      variants that influenced the growth rate by 25 per cent. RESULTS: For MMP-2, MMP
      9 and MMP-12 genotypes, growth rates were similar to the mean linear growth rate
      of 3.08 mm per year. For MMP-3, growth rates were 3.05 (for 5A5A), 3.19 (for
      5A6A) and 2.90 (for 6A6A) mm per year. For PAI-1, patients with 4G4G, 4G5G and
      5G5G genotypes had growth rates of 3.18, 2.92 and 3.47 mm per year, respectively,
      for aneurysms with a baseline diameter of 45.1, 44.6 and 46.2 mm. The increased
      growth rate for patients with PAI-1 5G5G genotype was not statistically
      significant (P = 0.061), although these patients had the lowest plasma PAI-1
      concentrations (P = 0.018). CONCLUSION: There was no evidence that any specific
      MMP polymorphism had a clinically significant effect on AAA expansion. The
      plasminogen system may have a small but clinically significant role in AAA
      development. Much larger studies would be needed to evaluate genes of smaller
      effect.

PMID- 16082624
TI  - Distributed current estimates using cortical orientation constraints.
AB  - Distributed source models of magnetoencephalographic (MEG) and
      electroencephalographic (EEG) data employ dense distributions of current sources
      in a volume or on a surface. Previously, anatomical magnetic resonance imaging
      (MRI) data have been used to constrain locations and orientations based on
      cortical geometry extracted from anatomical MRI data. We extended this approach
      by first calculating cortical patch statistics (CPS), which for each patch
      corresponding to a current source location on the cortex comprise the area of the
      patch, the average normal direction, and the average deviation of the surface
      normal from its average. The patch areas were then incorporated in the forward
      model to yield estimates of the surface current density instead of dipole
      amplitudes at the current locations. The surface normal data were employed in a
      loose orientation constraint (LOC), which allows some variation of the current
      direction from the average normal. We employed this approach both in the l(2)
      minimum-norm estimates (MNE) and in the more focal l(1) minimum-norm solutions,
      the minimum-current estimate (MCE). Simulations in auditory and somatosensory
      areas with current dipoles and 10- or 20-mm diameter cortical patches as test
      sources showed that applying the LOC can increase localization accuracy. We also
      applied the method to in vivo auditory and somatosensory data.

PMID- 16082625
TI  - Work disability and its economic effect on 55-64-year-old adults with rheumatoid
      arthritis.
AB  - OBJECTIVE: To examine the extent and financial impact of work disability among
      older workers with rheumatoid arthritis (RA). METHODS: Year 2002 data from 5,419
      subjects with RA < 65 years of age in the National Data Bank for Rheumatic
      Diseases were used, along with US population data. Measures of work disability
      were employment status, part-time work, sick day use, and limitation in work
      demands; the latter was assessed by the Work Limitations Questionnaire (WLQ).
      Measures of financial status were median household income and poverty level
      income. Statistical procedures included logistic and linear regression,
      Wilcoxon's rank sum test, and chi-square test. RESULTS: Despite being better
      educated, subjects with RA ages 55-64 years had lower employment rates than
      individuals of the same age in the US (women 40% versus 53% and men 54% versus
      66%). These older subjects with RA had stopped working more often than younger
      subjects with RA, and more worked part time (40% versus 34%; P < 0.01). However,
      the older subjects used sick time less often than younger subjects (35% versus
      41%; P < 0.01) and were similarly limited in job demands, e.g., physical demands
      (mean WLQ subscale score 27.0 versus 26.6; P = 0.65). Median household income of
      older employed subjects was 20,000 dollars greater than that of retired subjects;
      56% of retired subjects had incomes lower than US median income versus 32% of
      employed subjects, and 11% had income below the poverty level. CONCLUSION:
      Premature work cessation in persons with RA ages 55-64 years is a serious problem
      that needs to be addressed.

PMID- 16082626
TI  - Efficacy of glucosamine sulfate in knee osteoarthritis: comment on the article by
      Cibere et al.

PMID- 16082627
TI  - Comparison of disease progression and mortality of connective tissue disease
      related interstitial lung disease and idiopathic interstitial pneumonia.
AB  - OBJECTIVE: To compare disease progression and mortality between idiopathic
      interstitial pneumonia (IIP) and interstitial lung disease (ILD) due to
      connective tissue diseases (CTD) including scleroderma, rheumatoid arthritis,
      systemic lupus, polymyositis, dermatomyositis, Sjogren's syndrome, and mixed CTD.
      METHODS: A case-control study of patients with CTD-ILD (n = 46) and IIP controls
      (n = 51), seen at the University of Michigan between July 1,1998 and June 30,1999
      and followed until March 30, 2002, was conducted. Survival analysis and Cox
      regression were performed to estimate survival, accounting for demographic and
      clinical parameters, including pulmonary function tests and high resolution
      computed tomography (HRCT) diagnosis and scoring. RESULTS: Median followup time
      was 4.4 person-years. Five-year survival in the IIP group was 51.9% (95%
      confidence interval [95% CI] 30.8-69.4) versus 43.4% (95% CI 21.1-63.9) in the
      CTD-ILD group. There were no significant differences among HRCT diagnostic
      categories between IIP and CTD-ILD. A fibrotic score > or = 2 was associated with
      decreased survival among the entire group. Age at diagnosis and most recent
      forced vital capacity were significant predictors of mortality when adjusted for
      IIP versus CTD-ILD diagnosis, sex, and interstitial score. CONCLUSION: Contrary
      to expectation, CTD-ILD compared with IIP appears to be associated with a worse
      prognosis when adjusted for age. A higher fibrotic score is suggestive of
      decreased survival.

PMID- 16082628
TI  - Muscle metabolites, detected in urine by proton spectroscopy, correlate with
      disease damage in juvenile idiopathic inflammatory myopathies.
AB  - OBJECTIVE: To assess for novel markers of muscle damage using urinary muscle
      metabolites by 1H magnetic resonance spectroscopy in patients with juvenile
      idiopathic inflammatory myopathy (IIM). METHODS: Creatine (Cr), choline (Cho),
      betaine (Bet), glycine (Gly), trimethylamine oxide (TMAO), and several other
      metabolites were measured in first morning void urine samples from 45 patients
      with juvenile IIM and from 35 healthy age-matched controls, and correlated with
      measures of myositis disease activity and damage. Urinary metabolite to age
      adjusted creatinine (Cn) ratios were examined. RESULTS: Age-adjusted initial
      Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios were higher in patients with
      juvenile IIM than controls (P < 0.01). Cr:Cn ratios showed significant
      correlations with physician-assessed global disease damage (Spearman rs = 0.37; P
      = 0.01), Steinbrocker functional class (rs = 0.35; P = 0.02), serum Cr (rs =
      0.72; P = 0.001), and lactate dehydrogenase (rs = 0.34; P = 0.03) levels. Cho:Cn
      (rs = 0.3; P = 0.05), Gly:Cn (rs = 0.33; P = 0.03), and TMAO:Cn (rs = 0.36; P =
      0.02) ratios showed a significant correlation with serum aldolase levels. Cho:Cn
      ratios also showed a significant correlation with aspartate aminotransferase
      levels (rs = 0.35; P = 0.02). A linear regression model was used to evaluate the
      factors influencing urinary Cr:Cn ratios in the 43 patients with data sets
      available at the initial visit. The regression model explained 73% of the
      variation in Cr:Cn ratios. The most significant factor was the physician-assessed
      global disease damage (R2 = 0.50, P = 0.015). CONCLUSION: Urinary Cr:Cn, Cho:Cn,
      Bet:Cn, Gly:Cn, and TMAO:Cn ratios are elevated in juvenile IIM and Cr:Cn
      correlates strongly with global disease damage. The Cr:Cn ratio may have
      potential utility as a marker of myositis disease damage.

PMID- 16082630
TI  - Validation of single-factor structure and scoring protocol for the Health
      Assessment Questionnaire-Disability Index.
AB  - OBJECTIVE: The extensively used Health Assessment Questionnaire Disability Index
      (HAQ-DI) has been well received by the research and clinical community, notably
      because of its measurement strengths including reliability and stability of
      scores over time, utility in observational studies and clinical trials,
      predictive relationship with morbidity and mortality in rheumatoid arthritis
      (RA), and its translation for use in different countries. However, HAQ-DI scoring
      has not been validated. The purpose of this study was to examine the structural
      validity of the HAQ-DI and evaluate the latent factors underlying HAQ-DI scoring.
      METHODS: This study used a cross-validation approach on a total of 278 patients
      with RA. Exploratory and confirmatory factor analyses were performed. RESULTS:
      Results yielded a single-factor HAQ-DI score, which favored the current scoring
      system of the HAQ-DI. Additionally, modification indices suggested improved model
      fit with the secondary inclusion of correlated residual scores from a motor
      skills subdomain. CONCLUSION: The current study provides the first validation of
      the HAQ-DI scoring system as determined by its latent factor structure. In
      addition, the findings suggest some benefit from a secondary interpretation of
      the scores based on domains that measure motor skills.

PMID- 16082631
TI  - Interstitial lung disease in connective tissue diseases: what are the important
      questions?

PMID- 16082632
TI  - Musculoskeletal ultrasound in rheumatology: a radiologic perspective.

PMID- 16082633
TI  - Glucocorticoid use and serum lipid levels in US adults: the Third National Health
      and Nutrition Examination Survey.
AB  - OBJECTIVE: It has been generally perceived that glucocorticoids adversely affect
      serum lipid levels, although results of prospective studies have suggested the
      contrary. In this study, we sought to examine the relationship between
      glucocorticoid use and lipid profiles in a nationally representative sample of
      subjects. METHODS: Using data from 15,004 participants ages 20 years and older in
      The Third National Health and Nutrition Examination Survey (1988-1994), we
      examined the relationship between glucocorticoid use and serum lipid profiles.
      Glucocorticoid use was determined from the household interview regarding
      prescription medication use. We used multivariate linear regression to adjust for
      age, sex, race or ethnicity, education, smoking status, body mass index, physical
      activity, alcohol consumption, energy fraction from protein and carbohydrates,
      and total energy intake. RESULTS: Glucocorticoid use was associated with a higher
      serum high-density lipoprotein (HDL) cholesterol level and a lower ratio of total
      cholesterol-to-HDL cholesterol among subjects ages 60 years or older
      (multivariate difference 9.0 mg/dl [95% confidence interval (95% CI) 3.9, 14.1]
      and -0.6 mg/dl [95% CI -0.9, -0.3], respectively) but not among those younger
      than age 60 years (multivariate difference -1.5 mg/dl [95% CI -5.4, 2.5] and 0.1
      mg/dl [95% CI -0.3, 0.5], respectively). Correspondingly, glucocorticoid use was
      associated with a higher serum apolipoprotein A-I (Apo A-I) level and a lower Apo
      A-I:Apo B ratio (multivariate difference 12.1 mg/dl [95% CI 2.9, 21.3] and 0.16
      mg/dl [95% CI 0.03, 0.29], respectively) only among subjects ages 60 years or
      older. Inhalation/intranasal glucocorticoid use was also associated with a higher
      serum HDL cholesterol level (multivariate difference 4.9 mg/dl [95% CI 0.3, 9.5])
      only among subjects ages 60 years or older. CONCLUSION: Our results suggest that
      glucocorticoid use is not associated with an adverse lipid profile in the US
      population and may be associated with a favorable lipid profile among persons
      ages 60 years or older, in concordance with previous prospective studies.

PMID- 16082634
TI  - Quantitative assessments of the effects of a single exercise session on muscles
      in juvenile dermatomyositis.
AB  - OBJECTIVE: To investigate the short-term effects of exercise on muscle
      inflammation in children with juvenile dermatomyositis (juvenile DM). Magnetic
      resonance imaging (MRI), muscle strength, and blood parameters were used as
      outcome measures. METHODS: Children with active juvenile DM, inactive juvenile
      DM, and healthy children were assessed for muscle strength (using myometry) and
      function, and MRI T2-weighted relaxation time measurement; blood was obtained
      from patients with juvenile DM. A standardized physiotherapy-led exercise program
      was completed, and the MRI was performed immediately afterwards. All children
      were reassessed with myometry and MRI at 30 minutes and 60 minutes, and repeat
      blood tests were performed at 60 minutes for the patients with juvenile DM.
      RESULTS: Ten children with active juvenile DM, 10 with inactive juvenile DM, and
      20 healthy controls completed the study. Muscle inflammation assessed by MRI,
      myometry, and blood parameters did not change significantly in response to
      exercise either immediately after or up to 60 minutes after the exercise program
      in any group. CONCLUSION: In the short term, a single bout of exercise does not
      change the degree of inflammation within the muscles of children with active or
      inactive juvenile DM or in healthy children. The data suggest that, at least in
      this time period, there is no evidence that exercise increases the inflammation
      within the muscles. We propose therefore that a moderate exercise program is safe
      for children with juvenile DM.

PMID- 16082635
TI  - Incidence rates of arterial and venous thrombosis after diagnosis of systemic
      lupus erythematosus.

PMID- 16082636
TI  - Granulomatous lung disease occurring during etanercept treatment.

PMID- 16082637
TI  - Lymphadenopathy, cough, and fever in a 51-year-old woman with systemic lupus
      erythematosus: case report of lymphomatoid granulomatosis.

PMID- 16082639
TI  - Spondyloarthritis Research Consortium of Canada magnetic resonance imaging index
      for assessment of spinal inflammation in ankylosing spondylitis.
AB  - OBJECTIVE: To develop a feasible magnetic resonance imaging (MRI)-based scoring
      system for spinal inflammation in patients with spondylarthropathy that requires
      minimal scan time, does not require contrast enhancement, evaluates the extent of
      lesions in 3 dimensional planes, and limits the number of vertebral levels that
      are scored because MRI demonstrates characteristic inflammatory lesions in the
      spine of patients with ankylosing spondylitis (AS) prior to the development of
      typical features on plain radiographic. METHODS: Our scoring method was based
      entirely on the assessment of increased signal denoting bone marrow edema on T2
      weighted STIR sequences. Blinded MRI films were assessed in random order at 2
      sites by 3 blinded readers at each of the 2 sites (the Universities of Alberta
      and Toronto). Intra- and interreader reliability was assessed by intraclass
      correlation coefficient. The 24-week response of patients with AS randomized to
      infliximab:placebo (8:3) was assessed by effect size and standardized response
      mean. RESULTS: An initial analysis of all discovertebral units (DVUs) in the
      spine of 11 patients demonstrated a mean of 3.2 (95% confidence interval 3.2,
      5.2) affected units, while limiting the scoring to a maximum of 6 units captured
      most of the affected units. We scanned 11 patients with AS with clinically active
      disease and 20 additional patients randomized to a 24-week trial of either
      infliximab or placebo. Intraobserver reproducibility for the 6-DVU STIR score
      ranged from 0.93 to 0.98 (P < 0.0001). Interobserver reproducibility of scores by
      readers from both sites was 0.79 (P < 0.0001) for status score and 0.82 (P <
      0.0001) for change score. Analysis of pretreatment and posttreatment scores for
      all 20 patients randomized to infliximab/placebo showed a large degree of
      responsiveness (standardized response mean = 0.87). Reproducibility and
      responsiveness were only slightly improved by using contrast enhancement with
      gadolinium diethylenetriaminepentaacetic acid. CONCLUSION: The Spondyloarthritis
      Research Consortium of Canada MRI index is a feasible, reproducible, and
      responsive index for measuring spinal inflammation in AS.

PMID- 16082640
TI  - Reductions in health-related quality of life in patients with ankylosing
      spondylitis and improvements with etanercept therapy.
AB  - OBJECTIVE: To assess the impact of ankylosing spondylitis (AS) on patient health
      related quality of life (HRQOL) relative to both the general US and chronically
      ill populations, and to evaluate whether etanercept therapy can reverse
      impairments in HRQOL due to AS. METHODS: Two AS patient populations were
      evaluated: patients with AS from a US clinical trial who were randomized to
      receive either etanercept (n = 20) or placebo (n = 20) for 16 weeks, and placebo
      treated patients from a multinational sample who subsequently received etanercept
      (n = 129) during a 48-week, open-label extension study. A sample from the US
      general population and patients with other medical conditions derived from the
      National Survey of Functional Health Status were used as comparators to evaluate
      the relative impact of active AS on HRQOL, as measured by the Short Form 36 (SF
      36) questionnaire. RESULTS: At baseline, patients with AS in both the US and
      multinational samples had significantly lower scores than the US general
      population on all 8 SF-36 scales. Compared with patients with other medical
      conditions, patients with AS had the lowest scores in the physical domains-
      Physical Functioning, Role Physical, and Bodily Pain. Impairments in SF-36 scores
      for psychosocial domains, such as Social Functioning, Role Emotional, and Mental
      Health, were somewhat less pronounced in patients with AS. Treatment with
      etanercept significantly improved the HRQOL of patients with AS on all 8 SF-36
      scales, especially in the same physical domains that showed the greatest
      impairments prior to treatment (Physical Functioning, Role Physical, and Bodily
      Pain). CONCLUSION: Patients with active AS despite conventional therapy have
      significantly reduced HRQOL across a wide range of domains. These reductions are
      most pronounced in the physical domains and exceed those seen in many other
      chronic diseases. Etanercept therapy significantly improves patient HRQOL,
      indicating that decrements in HRQOL due to AS may be at least partly reversible.

PMID- 16082641
TI  - Hospitalizations attributable to arthritis, smoking, and hypertension: a
      comparison based on NHEFS and NHANES III.
AB  - OBJECTIVE: To compare the impact of arthritis, smoking, and residual hypertension
      on the annual rate of hospital admissions in adults ages 45-74, because arthritis
      imposes a heavy health burden on individuals and higher medical costs on the
      nation. METHODS: A simulation model was used to estimate annual hospital
      admissions attributable to each risk factor for all adults ages 45-74, and for
      overweight adults in that age bracket, from the Third National Health and
      Nutrition Examination Survey (NHANES III). RESULTS: Arthritis accounted for 6.2%
      of annual hospital admissions (8.1 admissions per 1,000 NHANES III adults).
      Current smoking accounted for a slightly larger share of admissions (7.0% or 9.1
      admissions per 1,000 adults) and residual hypertension accounted for a smaller
      share (2.3% or 3.0 admissions per 1,000 adults). Because arthritis is more
      prevalent in overweight adults, it accounted for 7.4% of admissions (11.0
      admissions per 1,000 annually in this group), compared with 5.8% for smoking (8.6
      admissions per 1,000). CONCLUSION: Although the impact of smoking and
      hypertension receives more attention from the media, the impact of arthritis on
      hospitalizations is substantial. This finding provides additional support for the
      goals of the National Arthritis Action Plan.

PMID- 16082642
TI  - Interventions for foot disease in rheumatoid arthritis: a systematic review.
AB  - OBJECTIVE: To systematically review medical and surgical foot intervention
      studies in rheumatoid arthritis (RA), focusing on clinical efficacy, study
      quality, and risk of harm. METHODS: We searched appropriate databases using a
      combination of the terms "rheumatoid arthritis" and "foot" against terms
      indicating treatment; we also hand-searched references. We selected articles in
      English (1968-2003) comprising randomized controlled trials (RCTs), controlled
      clinical trials (CCTs), prospective observational studies, and large
      retrospective observational surgical studies (> 50 cases). RCT quality was
      examined using Jadad scoring; other designs were assessed qualitatively. RESULTS:
      Inclusion criteria were met by 33 of 894 identified studies, comprising 5 RCTs
      and 1 CCT (all nonsurgical), 15 prospective observational studies (8 nonsurgical,
      7 surgical), and 12 large retrospective studies (all surgical). Functional,
      custom-designed and semirigid orthoses and extra-depth shoes were effective in
      single RCTs of variable quality; no comparative studies have been conducted. This
      finding was supported by a CCT and prospective observational studies. There was
      no evidence of harm. There were no controlled trials of surgery. Prospective
      observational studies suggest that forefoot arthroplasty and first
      metatarsophalangeal joint implants, but not plantar callous debridement, are
      effective. Comparative retrospective analyses suggest that some procedure
      variants may be better, and surgery may relieve pain better than orthoses.
      Infection was the main risk. CONCLUSION: RCT evidence shows that orthoses and
      special shoes are likely to be beneficial in patients with RA. The only evidence
      of benefit from surgery comes from observational studies, because no RCTs have
      been conducted. Further RCT evidence is needed, although well-designed
      observational studies may be helpful.

PMID- 16082643
TI  - Decreased pain and synovial inflammation after etanercept therapy in patients
      with reactive and undifferentiated arthritis: an open-label trial.
AB  - OBJECTIVE: Elevated levels of tumor necrosis factor alpha (TNFalpha) have been
      identified in the synovium of patients with reactive and undifferentiated
      arthritis, implicating TNFalpha in the pathogenesis of these disorders. This
      finding has provided a rationale for the use of TNFalpha antagonists in the
      treatment of reactive arthritis; however, the possibility that the triggering
      microorganism might persist in affected joints and become activated with use of
      these agents has been of concern. METHODS: The efficacy and safety of etanercept
      (25 mg subcutaneous twice weekly) in 16 patients with undifferentiated or
      reactive arthritis was assessed in a 6-month open-label trial. Synovial biopsies
      were performed before and after treatment with etanercept. Polymerase chain
      reaction (PCR) analysis was performed on the synovial biopsy samples to evaluate
      for the presence of nucleic acid material of bacterial organisms. Outcome
      measures including tender and swollen joint counts, pain assessment on a 10-point
      visual analog scale, and functional ability as measured by the Health Assessment
      Questionnaire were determined before and after etanercept therapy. RESULTS: Ten
      of 16 patients completed the trial. Six patients withdrew, but none had a
      worsening of arthritis or infection. Of the 10 completers, 9 could be classified
      as treatment responders, despite the evidence of bacterial organisms on PCR
      analysis prior to initiating etanercept in 3 patients; 2 patients became PCR
      negative on etanercept. Five of 6 patients with adequate synovial biopsy
      specimens showed improvement, but not normalization of histology. CONCLUSION:
      Etanercept was well-tolerated without clinical exacerbation of any suspected
      underlying infections and appeared to provide therapeutic benefit in our cohort
      of patients with reactive and undifferentiated arthritis.

PMID- 16082644
TI  - Pilot clinical trial of dehydroepiandrosterone for Sjogren's syndrome: comment on
      the article by Pillemer et al.

PMID- 16082645
TI  - Discoid lupus erythematosus after tattoo: Koebner phenomenon.

PMID- 16082646
TI  - Impact of fibromyalgia pain on health-related quality of life before and after
      treatment with tramadol/acetaminophen.
AB  - OBJECTIVE: To assess health-related quality of life (HRQOL) in patients with
      moderate-to-severe fibromyalgia pain compared with the general population, and to
      assess the relationship between pain severity and HRQOL before and after
      treatment with an analgesic. METHODS: Data were obtained from a randomized,
      double-blind study of patients with moderate-to-severe fibromyalgia pain.
      Patients received either tramadol/acetaminophen or placebo 4 times/day as needed
      for 91 days. HRQOL was measured with the Short Form 36 Health Survey (SF-36) and
      the Fibromyalgia Impact Questionnaire (FIQ). Baseline HRQOL scores were compared
      with a national sample of noninstitutionalized adults and a sample of patients
      with impaired HRQOL due to congestive heart failure. Patients with fibromyalgia
      were divided into tertiles by change in pain severity, and SF-36 scores were
      compared across the tertiles. Mean changes in SF-36 and FIQ scores were compared
      between treatment groups. RESULTS: Patients with fibromyalgia scored lower than
      the US norm on all SF-36 scales (P < 0.0001) and lower than patients with
      congestive heart failure on most scales. More severe pain was associated with
      greater impairment of HRQOL compared with less severe pain (P < 0.0001). Patients
      in the highest tertile for improved pain severity had greater improvement in
      HRQOL scores than patients in the lower tertiles. Compared with patients who
      received placebo (n = 157), patients treated with tramadol/acetaminophen (n =
      156) showed greater improvement on SF-36 physical functioning, role physical,
      bodily pain, and physical summary scales, as well as FIQ scales for ability to do
      job, pain, and stiffness (P < 0.01). CONCLUSION: Moderate-to-severe fibromyalgia
      pain significantly impairs HRQOL, and effective pain relief in these patients
      significantly increases HRQOL.

PMID- 16082648
TI  - Need for common internal controls when assessing the relative efficacy of
      pharmacologic agents using a meta-analytic approach: case study of cyclooxygenase
      2-selective inhibitors for the treatment of osteoarthritis.
AB  - OBJECTIVE: To evaluate the role of common internal controls in a meta-analysis of
      the relative efficacy of cyclooxygenase 2-selective inhibitors (coxibs) in the
      treatment of osteoarthritis (OA). METHODS: A systematic search of Medline and US
      Food and Drug Administration electronic databases was performed to identify
      randomized, placebo-controlled clinical trials of coxibs (etoricoxib, celecoxib,
      rofecoxib, valdecoxib) in patients with hip and/or knee OA. The effect size for
      coxibs and common active internal controls (nonsteroidal antiinflammatory drugs
      [NSAIDs], naproxen) were determined by the mean changes from baseline in Western
      Ontario and McMaster Universities Osteoarthritis Index pain subscores as compared
      with placebo. RESULTS: The effect size for all coxib groups combined (0.44)
      indicated greater efficacy as compared with placebo, but significant
      heterogeneity (P < 0.0001) was observed. Rofecoxib at dosages of 12.5 mg/day and
      25 mg/day and etoricoxib at a dosage of 60 mg/day had similar effect sizes (0.68
      and 0.73, respectively), but these effect sizes were comparatively greater than
      those for both celecoxib at dosages of 200 mg/day and 100 mg twice daily or
      valdecoxib at a dosage of 10 mg/day (0.26 and 0.16, respectively). The effect
      sizes for NSAIDs or naproxen versus placebo, as determined using data from
      rofecoxib/etoricoxib trials, were consistently higher than the effect sizes
      derived from trials of celecoxib/valdecoxib. Significant heterogeneity was
      present in the overall effect size for NSAIDs (P = 0.007) and naproxen (P = 0.04)
      groups based on data available from all coxib trials. CONCLUSION: Coxibs and
      common active internal controls showed larger effect sizes versus placebo in the
      rofecoxib/etoricoxib trials than in the celecoxib/valdecoxib trials. These
      findings suggest systematic differences among published coxib trials and
      emphasize the need for direct-comparison trials. In the absence of such trials,
      common internal controls should be assessed when performing indirect meta
      analytic comparisons.

PMID- 16082649
TI  - Arthritis onset and worsening self-rated health: a longitudinal evaluation of the
      role of pain and activity limitations.
AB  - OBJECTIVE: To longitudinally explore the hypothesized role of worsening pain and
      development of activity limitations as mediators in the relationship between
      arthritis onset and worsening self-rated health (SRH). METHODS: Data was obtained
      from the 1998/1999 and 2000/2001 cycles of the population-based Canadian
      longitudinal National Population Health Survey (n = 10,859; ages > or = 18;
      response rate: time 1 = 81.6%, time 2 = 89.2%). Respondents were asked about
      chronic conditions, pain, activity limitations, and self-perceived health; change
      over time was assessed. Change in effect of arthritis onset on worsening SRH upon
      considering potential mediators was assessed through multivariate logistic
      regression, controlling for sociodemographic characteristics and onset of other
      conditions. RESULTS: Worsening pain fully explained the effect of arthritis onset
      on worsening SRH; a portion of the effect of worsening pain was mediated by the
      development of activity limitation. Residual direct effect of arthritis onset was
      statistically insignificant. Worsening pain and development of activity
      limitations also mediated a portion of the effects of onset of other chronic
      conditions but to a lesser extent than arthritis onset. CONCLUSION: This is the
      first study to examine these relationships longitudinally. Identifying the role
      of mediators is necessary if target areas of prevention and/or management are
      sought, either at the individual or population level. Our results indicate that
      the development of arthritis has a significant impact on worsening SRH. Pain and
      development of activity limitations fully account for the relationship between
      arthritis onset and worsening SRH. High priority should be placed on prevention
      and management strategies for pain among people with arthritis.

PMID- 16082650
TI  - Direct medical costs of polymyalgia rheumatica.
AB  - OBJECTIVE: To describe the patterns of care and direct medical costs of
      polymyalgia rheumatica (PMR) to test the hypothesis that the direct medical costs
      incurred by patients with PMR are higher than costs incurred by age- and sex
      matched population-based controls from the same community. METHODS: The study
      population comprised 193 Olmsted County, Minnesota residents who were first
      diagnosed with PMR between January 1, 1987 and December 31, 1999. Inclusion
      criteria were as follows: age > or = 50 years; bilateral aching and morning
      stiffness (lasting > or = 30 minutes) persisting for at least 1 month and
      involving the neck, shoulders, or hip girdle regions; and an erythrocyte
      sedimentation rate (ESR) > or = 40 mm/hour. In patients who fulfilled the first 2
      criteria, but had a normal ESR, a rapid response to low-dose corticosteroids
      served as the third criterion. A total of 695 age- and sex-matched subjects
      without PMR served as control subjects. Billing data from the Olmsted County
      Healthcare Expenditure and Utilization Database (OCHEUD) were used to provide
      estimates of nationally representative unit costs in the year 2002 inflation
      adjusted dollars. All subjects were followed using the OCHEUD records until
      December 31, 2002 to assess the total direct medical costs. Generalized quantile
      regression modeling was used to estimate the effect of PMR on direct medical
      costs, after adjusting for age, sex, Charlson comorbidity score, number of
      hospital days, and number of radiographs. RESULTS: During the first year
      following diagnosis, subjects with PMR used a substantially higher number of
      outpatient services and laboratory tests compared with controls, but during the
      subsequent 4 years, there were no differences between the 2 groups. In age- and
      sex-adjusted analysis, PMR was associated with a significant incremental cost of
      2,233 dollars at the 10th percentile of costs and 27,712 dollars at the 90th
      percentile of costs. However, further adjustments for comorbidities, number of
      hospital days, radiographs, and imaging eliminated the incremental cost
      difference between the subjects with PMR and control subjects. PMR subjects were
      significantly more likely to have a history of myocardial infarction (odds ratio
      [OR] 1.78, 95% confidence interval [95% CI] 1.13, 2.82), peripheral vascular
      diseases (OR 2.21, 95% CI 1.37, 3.60), and cerebrovascular diseases (OR 1.60, 95%
      CI 1.08, 2.39) compared with the controls. CONCLUSION: Incremental direct medical
      costs associated with the management of PMR can be substantial, especially early
      in the disease course. These incremental costs appear to originate mainly from
      comorbid cardiovascular conditions that were shown to be more prevalent among
      subjects with PMR.

PMID- 16082651
TI  - The clinical rheumatoid arthritis articular damage score in Tunisian patients.

PMID- 16082652
TI  - Dehydroepiandrosterone versus placebo for Sjogren's syndrome: comment on the
      article by Pillemer et al.

PMID- 16082653
TI  - The 3-way stopcock: a useful adjunct in the practice of arthrocentesis.

PMID- 16082655
TI  - Perceived self-efficacy gained from, and health effects of, a rehabilitation
      program after hip joint replacement.
AB  - OBJECTIVE: To examine whether a routine multidisciplinary inpatient
      rehabilitation program can increase patient self-efficacy, and to investigate the
      effects of high self-efficacy at admission, and increases in self-efficacy, on
      health changes in patients who undergo such rehabilitation after hip joint
      replacement. METHODS: Participants in this longitudinal study were 1,065 patients
      who underwent inpatient rehabilitation after hip joint replacement.
      Questionnaires were administered at admission, discharge, and 6-month followup.
      The main outcome variables were disability, pain, depressive symptomatology, and
      self-efficacy to cope with disability and pain. RESULTS: Significant improvements
      from admission to discharge from the inpatient rehabilitation program in
      disability, pain, depressive symptoms, and self-efficacy were found. In addition,
      higher levels of self-efficacy at admission and larger increases in self-efficacy
      over the course of the program predicted larger health changes (i.e., greater
      decreases in disability, pain, and depressive symptoms). Results were generally
      similar for health changes from discharge to 6-month followup. CONCLUSION: A
      routine multidisciplinary inpatient rehabilitation program after hip joint
      replacement can result in enhanced self-efficacy.

PMID- 16082656
TI  - Age effects on diffusion tensor magnetic resonance imaging tractography measures
      of frontal cortex connections in schizophrenia.
AB  - Diffusion tensor magnetic resonance imaging (DT-MRI) has previously been used to
      investigate white matter tracts in schizophrenia, with inconsistent results. The
      aim of the study was to use a novel method for tract-specific measurements of
      fronto-temporal fasciculi in early-onset schizophrenia. We hypothesized that by
      making tract-specific measurements, clear diffusion abnormalities would be
      revealed in specific fasciculi in schizophrenia. Measurements of diffusion
      anisotropy and mean diffusivity were localized within fronto-temporal fasciculi
      by forming 3-D reconstructions of the cingulum, uncinate, superior longitudinal,
      and inferior fronto-occipital fasciculi using diffusion tensor tractography. We
      were limited in our ability to test our hypothesis by the important and
      surprising finding that age affected DT-MRI-based measures in schizophrenia
      patients in a different way from comparison subjects, most notably in the left
      superior longitudinal fasciculus. The youngest schizophrenia patients that we
      studied had lower diffusion anisotropy than age-matched comparison subjects, but
      this difference diminished with increasing age. The main conclusion of this study
      was that direct comparisons of absolute DT-MRI-based measures between individuals
      with schizophrenia and comparison subjects may be problematic and misleading
      because of underlying age-related differences in brain maturation between groups.

PMID- 16082657
TI  - Bilateral activation of the prefrontal cortex after strategic semantic cognitive
      training.
AB  - The prefrontal cortex (PFC) has been implicated in the ability to apply semantic
      organizational strategies during verbal encoding and episodic learning. However,
      there has been no direct evidence demonstrating which specific areas in the PFC
      are engaged after cognitive training using semantic organizational strategies in
      healthy adult human subjects. In this study, we investigated the effects of
      semantic strategic training on brain activity and changes in behavioral
      performance, after cognitive training, using functional MRI (fMRI). There was a
      significant activation in bilateral dorsolateral prefrontal (DLPF) and
      orbitofrontal (OFC) areas after cognitive training. These results demonstrate the
      engagement of bilateral DLPF and OFC cortex during strategic memory processes,
      particularly when mobilization and effort of effective use of strategies are
      required. The functional adaptations observed here may also shed light on some of
      the processes underlying recovery with cognitive rehabilitation in patient
      populations with brain injury.

PMID- 16082658
TI  - Nonlinear optical spectroscopy of chiral molecules.
AB  - We review nonlinear optical processes that are specific to chiral molecules in
      solution and on surfaces. In contrast to conventional natural optical activity
      phenomena, which depend linearly on the electric field strength of the optical
      field, we discuss how optical processes that are nonlinear (quadratic, cubic, and
      quartic) functions of the electromagnetic field strength may probe optically
      active centers and chiral vibrations. We show that nonlinear techniques open
      entirely new ways of exploring chirality in chemical and biological systems: The
      cubic processes give rise to nonlinear circular dichroism and nonlinear optical
      rotation and make it possible to observe dynamic chiral processes at ultrafast
      time scales. The quadratic second-harmonic and sum-frequency-generation phenomena
      and the quartic processes may arise entirely in the electric-dipole approximation
      and do not require the use of circularly polarized light to detect chirality.
      They provide surface selectivity and their observables can be relatively much
      larger than in linear optical activity. These processes also give rise to the
      generation of light at a new color, and in liquids this frequency conversion only
      occurs if the solution is optically active. We survey recent chiral nonlinear
      optical experiments and give examples of their application to problems of
      biophysical interest.

PMID- 16082659
TI  - Variability of EEG synchronization prior to and during observation and execution
      of a sequential finger movement.
AB  - The aim of this study was to test the validity of mirror neuron activity in
      humans through analysis of electroencephalographic (EEG) functional connectivity
      during an action not directed towards an object. We investigated changes in EEG
      interchannel synchronization prior to and during action execution and also prior
      to and during observation of the same action. Twelve participants observed a
      simple finger movement sequence. In a second testing session they physically
      executed the movement. EEGs were recorded from 19 active sites across the cortex.
      Activity was considered in four frequency bands (7-10 Hz, 10-13 Hz, 13-20 Hz, and
      20-30 Hz) using a new measure: synchronization likelihood. This technique
      considers rapid changes in signal synchronization and spatiotemporal patterns of
      coherence. The results revealed no statistically significant difference in
      synchronization likelihood between the observation and execution data. We found
      an increase in synchronization over a broad frequency range during task
      processing and suggest that this may reflect interregional cortical coupling of
      intricately and hierarchically interconnected networks that are active in a
      similar way during both observation and execution of a movement. While EEG may be
      insensitive to differences present during the observation and execution of a
      movement, the results of the present study shed some light on the general
      mechanisms of cognitive integration.

PMID- 16082660
TI  - A joint study based on the electron localization function and catastrophe theory
      of the chameleonic and centauric models for the Cope rearrangement of 1,5
      hexadiene and its cyano derivatives.
AB  - A novel interpretation of the chameleonic and centauric models for the Cope
      rearrangements of 1,5-hexadiene (A) and different cyano derivatives (B: 2,5
      dicyano, C: 1,3,4,6-tetracyano, and D: 1,3,5-tricyano) is presented by using the
      topological analysis of the electron localization function (ELF) and Thom's
      catastrophe theory (CT) on the reaction paths calculated at the B3LYP/6-31G(d,p)
      level. The progress of the reaction is monitorized by the changes of the ELF
      structural stability domains (SSD), each being change controlled by a turning
      point derived from CT. The reaction mechanism of the parent reaction A is
      characterized by nine ELF SSDs. All processes occur in the vicinity of the
      transition structure and corresponding to a concerted formation/breaking of C(1)
      C(6) and C(3)-C(4) bonds, respectively, together with an accumulation of charge
      density onto C(2) and C(5) atoms. Reaction B presents the same number of ELF SSDs
      as A, but a different order appears; the presence of 2,5-dicyano substituents
      favors the formation of C(1)-C(6) bonds over the breaking of C(3)-C(4) bond
      process, changing the reaction mechanism from a concerted towards a stepwise, via
      a cyclohexane biradical intermediate. On the other side, reaction C presents the
      same type of turning points but two ELF SSD less than A or B; there is an
      enhancement of the C(3)-C(4) bond breaking process at an earlier stage of the
      reaction by delocalizing the electrons from the C(3)-C(4) bond among the cyano
      groups. In the case of competitive effects of cyano subsituents on each moiety,
      as it is for reaction D, seven different ELF SSDs have been identified separated
      by eight turning points (two of them occur simultaneously). Both processes,
      formation/breaking of C(1)-C(6) and C(3)-C(4) bonds, are slightly favored with
      respect to the parent reaction (A), and the TS presents mixed electronic features
      of both B and C. The employed methodology provides theoretical support for the
      centauric nature (half-allyl, half-radical) for the TS of D.

PMID- 16082661
TI  - Identification and thermodynamic treatment of several types of large-amplitude
      motions.
AB  - We present a partially automated method for the thermodynamic treatment of large
      amplitude motions. Starting from the molecular geometry and the Hessian matrix,
      we evaluate anharmonic partition functions for selected vibrational degrees of
      freedom. Supported anharmonic vibration types are internal rotation and inversion
      (oscillation in a double-well potential). By heuristic algorithms, we identify
      internal rotations in most cases automatically from the Hessian eigenvectors, and
      we also estimate the parameters of anharmonic partition functions (e.g.,
      potential barrier, periodicity, and symmetry number) with thermodynamically
      sufficient precision. We demonstrate the validity of our schemes by comparison to
      pointwise calculated ab initio potential curves.

PMID- 16082662
TI  - In situ and online monitoring of hydrodynamic flow profiles in microfluidic
      channels based upon microelectrochemistry: concept, theory, and validation.
AB  - Herein, we propose a method for reconstructing any plausible macroscopic
      hydrodynamic flow profile occurring locally within a rectangular microfluidic
      channel. The method is based on experimental currents measured at single or
      double microband electrodes embedded in one channel wall. A perfectly adequate
      quasiconformal mapping of spatial coordinates introduced in our previous work
      [Electrochem. Commun. 2004, 6, 1123] and an exponentially expanding time grid,
      initially proposed [J. Electroanal. Chem. 2003, 557, 75] in conjunction with the
      solution of the corresponding variational problem approached by the Ritz method
      are used for the numerical reconstruction of flow profiles. Herein, the concept
      of the method is presented and developed theoretically and its validity is tested
      on the basis of the use of pseudoexperimental currents emulated by simulation of
      the diffusion-convection problem in a channel flow cell, to which a random
      Gaussian current noise is added. The flow profiles reconstructed by our method
      compare successfully with those introduced a priori into the simulations, even
      when these include significant distortions compared with either classical
      Poiseuille or electro-osmotic flows.

PMID- 16082663
TI  - A colloidal Au monolayer modulates the conformation and orientation of a protein
      at the electrode/solution interface.
AB  - The orientation and conformation of adsorbed cytochrome c (cyt c) at the
      interface between an electrode modified with colloidal Au and a solution were
      studied by electrochemical, spectroscopic, and spectroelectrochemical techniques.
      The results indicate that the colloidal Au monolayer formed via preformation of
      an organic self-assembled monolayer (SAM) can increase the electronic coupling
      between the SAM and cyt c in the same manner as bifunctional molecular bridges,
      one functional group of which is bound to the electrode surface while the other
      interacts with the protein surface. The approach of cyt c to the modified
      electrode/solution interface can be assisted by strong interactions of the
      intrinsic charge of colloidal particles with cyt c, while the heme pocket remains
      almost unchanged due to the screening effect of the negatively charged field
      created by the intrinsic charge. The conformational changes of cyt c induced by
      its adsorption at a bare glassy carbon electrode/solution interface and the
      effect of the electric field on the ligation state of the heme can be avoided at
      the colloidal-Au-modified electrode/solution interface. Finally, a possible model
      for the adsorption orientation of cyt c at the colloidal-Au-modified
      electrode/solution interface is proposed.

PMID- 16082664
TI  - Structural heterogeneity in DNA: temperature dependence of 2-aminopurine
      fluorescence in dinucleotides.
AB  - The fluorescent base analogue 2-aminopurine is a sensitive probe for local
      dynamics of DNA. Its fluorescence is quenched by interaction with the neighboring
      bases, but the underlying mechanisms are still under investigation. We studied 2
      aminopurine fluorescence in dinucleotides with each of the natural bases.
      Consistently, two of the four fluorescence-decay components depend strongly on
      temperature. Our results indicate that these components are due to the excited
      state dynamics of a single conformational state. We propose a variation of the
      gating model in which transient unstacking occurs in the excited state.

PMID- 16082665
TI  - Kinetics of the initial steps of G protein-coupled receptor-mediated cellular
      signaling revealed by single-molecule imaging.
AB  - We report on an in vivo single-molecule study of the signaling kinetics of G
      protein-coupled receptors (GPCR) performed using the neurokinin 1 receptor (NK1R)
      as a representative member. The NK1R signaling cascade is triggered by the
      specific binding of a fluorescently labeled agonist, substance P (SP). The
      diffusion of single receptor-ligand complexes in plasma membrane of living HEK
      293 cells is imaged using fast single-molecule wide-field fluorescence microscopy
      at 100 ms time resolution. Diffusion trajectories are obtained which show intra-
      and intertrace heterogeneity in the diffusion mode. To investigate universal
      patterns in the diffusion trajectories we take the ligand-binding event as the
      common starting point. This synchronization allows us to observe changes in the
      character of the ligand-receptor-complex diffusion. Specifically, we find that
      the diffusion of ligand-receptor complexes is slowed down significantly and
      becomes more constrained as a function of time during the first 1000 ms. The
      decelerated and more constrained diffusion is attributed to an increasing
      interaction of the GPCR with cellular structures after the ligand-receptor
      complex is formed.

PMID- 16082666
TI  - Molecular dynamics simulation of water near nanostructured hydrophobic surfaces:
      interfacial energies.
AB  - We present results from molecular dynamics simulations of water near structured
      hydrophobic surfaces. The surface structures reported herein are a planar alkane
      crystal as a reference and crystals with a hole and a protrusion of approximately
      2.5 nm diameter and 0.5 nm depth or height. All indicators show that surface
      structuring increases the hydrophobicity: The water density is reduced near the
      structure elements, and the number of residual contacts between water and the
      surface decreases by about 40 % with respect to the planar surface. Thermodynamic
      integration shows that the interfacial energy of the structured surfaces is about
      7 mJ m(-2) higher for structured surfaces than for the planar surface. The
      hydrophobicity increases by a similar amount for the hole and the protrusion
      geometries compared to the planar surface.

PMID- 16082667
TI  - Photophysical characterization of light-emitting poly(indenofluorene)s.
AB  - Time-resolved photoluminescence spectroscopy experiments of three poly(2,8
      indenofluorene) derivatives bearing different pendant groups are presented. A
      comparison of the photophysical properties of dilute solutions and thin films
      provides information on the chemical purity of the materials. The photophysical
      properties of poly(2,8-indenofluorene)s are correlated with the morphological
      characteristics of their corresponding films. Wide-angle X-ray scattering
      experiments reveal the order in these materials at the molecular level. The
      spectroscopic results confirm the positive impact of a new synthetic approach on
      the spectral purity of the poly(indenofluorene)s. It is concluded that complete
      side-chain substitution of the bridgehead carbon atoms C-6 and C-12 in the
      indenofluorene unit, prior to indenofluorene ring formation, reduces the
      probability of keto formation. Due to the intrinsic chemical purity of the
      arylated derivative, identification of a long-delayed spectral feature, other
      than the known keto band, is possible in the case of thin films. Controlled
      doping experiments on the arylated derivative with trace amounts of an
      indenofluorene-monoketone provide quantitative information on the rates of two
      major photophysical processes, namely, singlet photoluminescence emission and
      singlet photoluminescence quenching. These results allow the determination of the
      minimum keto concentration that can affect the intrinsic photophysical properties
      of this polymer. The data suggest that photoluminescence quenching operates in
      the doped films according to the Stern-Volmer formalism.

PMID- 16082671
TI  - The structure and conformations of 2-thiophenecarboxaldehyde obtained from
      partially averaged dipolar couplings.
AB  - The proton NMR spectra of samples of 2-thiophenecarboxaldehyde dissolved in a
      nematic liquid crystalline solvent, including those from all five singly labelled
      13C isotopomers, have been obtained. These have been analysed to yield sets of
      partially averaged dipolar couplings which have been used to determine the
      structure and the relative amounts of the cis and trans forms, which are the two
      minimum-energy structures generated by rotation about the ring-aldehyde bond. A
      procedure for applying vibrational corrections to the dipolar couplings in the
      presence of large amplitude motions is discussed.

PMID- 16082672
TI  - A theoretical description of elastic pillar substrates in biophysical
      experiments.
AB  - Arrays of elastic pillars are used in biophysical experiments as sensors for
      traction forces. The evaluation of the forces can be complicated if they are
      coupled to the pillar displacements over large distances. This is the case if
      many of the pillars are interconnected by elastic linkages as, for example, in
      fiber networks that are grown on top of pillars. To calculate the traction forces
      in such a network, we developed a set of nonlinear inhomogeneous equations
      relating the forces in the linking elements to the resulting pillar deflections.
      We chose a homogeneous, activated two-dimensional network of cytoskeletal actin
      filaments to illustrate that a pillar substrate is generally not a force sensor
      but a force-gradient sensor. In homogeneous networks the forces acting along the
      filaments can be approximated by analyzing only pillar deflections in the edge
      zones of the substrate and by integration over the corresponding force gradients.

PMID- 16082673
TI  - Ab initio studies of ClO(x) reactions: prediction of the rate constants of
      ClO+NO2 for the forward and reverse processes.
AB  - The potential-energy surface for the reaction of ClO with NO2 has been
      constructed at the CCSD(T)/6-311+G(3df)//B3LYP/6-311+G(3df) level of theory. Six
      ClNO3 isomers are located; these are ClONO2, pc-ClOONO, pt-ClOONO, OClNO2, pt
      OClONO, pc-OClONO, with predicted energies relative to the reactants of -25.6, 
      0.5, 1.0, 1.9, 12.2 and 13.6 kcal mol-1, and heats of formation at 0 K of 7.8,
      32.9, 34.4, 35.5, 45.6 and 47.0 kcal mol-1, respectively. Isomerizations among
      them are also discussed. The rate constants for the low-energy pathways have been
      computed by statistical theory calculations. For the association reaction
      producing exclusively ClONO2, the predicted low- and high-pressure-limit rate
      constants in N2 for the temperature range of 200-600 K can be represented by:
      (N2)=3.19 x 10-17 T-5.54 exp(-384 K/T) cm6 molecule-2 s-1 and =3.33 x 10-7 T-1.48
      exp(-18 K/T) cm3 molecule-1 s-1. The predicted low- and high-pressure-limit rate
      constants for the decomposition of ClONO2 in N2 at 200-600 K can be expressed,
      respectively, by =6.08 x 1013 T-6.54 exp(-13813 K/T) cm3 molecule-1 s-1 and =4.59
      x 1023 T-2.43 exp(-13437 K/T) s-1. The predicted values compare satisfactorily
      with available experimental data. The reverse Cl+NO3 reaction was found to be
      independent of the pressure, giving exclusively ClO+NO2; the predicted rate
      constant can be expressed as k(Cl+NO3)=1.19 x 10-9 T-0.60 exp(58 K/T) cm3
      molecule-1 s-1..

PMID- 16082674
TI  - Afferents of the ventral tegmental area in the rat-anatomical substratum for
      integrative functions.
AB  - The ventral tegmental area (VTA) is critically important to an organism's
      capacity to detect rewards and novelty and to enlist appropriate behavioral
      responses. Although there has been substantial progress concerning information
      processing at the single cell and molecular levels in the VTA, our knowledge of
      its overall afferent connections is based principally on the benchmark
      description by Phillipson ([1979] J. Comp. Neurol. 187:117-144). Given that,
      since then, the sensitivity of tracing methods and knowledge about the
      organization of brain structures have increased considerably, we undertook to
      reevaluate the VTA afferents of the rat. The retrograde tracer Fluoro-Gold was
      injected into different parts of the VTA, and labeled neurons were visualized by
      immunocytochemistry. Retrogradely labeled neurons were not confined to nuclei but
      rather constituted an elongated formation stretching from the prefrontal cortex
      rostrally to the medulla oblongata caudally. In the case of descending afferents,
      this formation was centered on the medial forebrain bundle and the fasciculus
      retroflexus. The input to the VTA in general was bilateral, with a smaller
      descending and comparable ascending projection from the contralateral side.
      Injections of the anterograde tracers Phaseolus vulgaris-leucoagglutinin or
      biotinylated dextran amine into selected forebrain structures revealed a
      surprisingly sparse terminal arborization in the VTA. Furthermore, structures
      projecting to the VTA innervate other brain areas with similar or greater
      robustness, which in turn also provide a strong input to the VTA, indicating an
      anatomical network. Given the importance of the VTA in basic behaviors, this
      organization might provide a basis for an extraordinary level of afferent
      integration.

PMID- 16082675
TI  - Comparative localization of two serotonin receptors and sensorin in the central
      nervous system of Aplysia californica.
AB  - Aplysia californica is a powerful model for understanding the cellular and
      molecular mechanisms underlying modulation of neuronal plasticity and learning.
      In the central nervous system of Aplysia, serotonin is associated with various
      behaviors. For example, it induces short-, intermediate-, and long-term synaptic
      changes in sensory neurons during learning and inhibits the afterdischarge of the
      bag cells that initiate egg-laying behavior. Little is known about the nature and
      contribution of serotonin receptors involved in the numerous serotonin-mediated
      physiological responses in Aplysia. Recently, two G(i)-coupled serotonin
      receptors (5-HT(ap1) and 5-HT(ap2)) were cloned. We now report that, by using in
      situ hybridization to express the profile of these receptors, we are able to gain
      critical insight into their roles in the behavior of Aplysia. We compared their
      distribution to that of sensorin-A, a peptide specifically found in sensory
      neurons. We wished to determine their involvement in some simple forms of
      behavioral modifications. 5-HT(ap1) and 5-HT(ap2) mRNAs are expressed in all
      ganglia of the Aplysia central nervous system. Stronger signal was observed with
      the 5-HT(ap2) antisense probe than with the 5-HT(ap1) antisense probe. Notably,
      mRNA coding for the receptors was found in several identified neurons, in the bag
      cells, in characterized serotonergic neurons, and in neurons of the
      mechanosensory clusters that expressed sensorin. We also observed heterogeneity
      of receptor expression between R2 and LPl1 and among neurons of a single cluster
      of sensory neurons. These results suggest that 5-HT(ap1) and 5-HT(ap2) receptors
      may regulate the response to serotonin and/or its release in several neurons.

PMID- 16082676
TI  - Mediodorsal thalamic afferents to layer III of the rat prefrontal cortex:
      synaptic relationships to subclasses of interneurons.
AB  - The mediodorsal nucleus of the thalamus (MD) represents the main subcortical
      structure that projects to the prefrontal cortex (PFC) and it regulates key
      aspects of the cognitive functions of this region. Within the PFC, GABA local
      circuit neurons shape the activity patterns and hence the "memory fields" of
      pyramidal cells. Although the connections between the MD and PFC are well
      established, the ultrastructural relationships between projecting fibers from the
      MD and different subclasses of GABA cells in the PFC are not known. In order to
      address this issue in the rat, we examined MD axons labeled by tract-tracing in
      combination with immunogold-silver to identify different calcium-binding proteins
      localized within separate populations of interneurons. Electron micrographic
      examination of PFC sections from these animals revealed that MD terminals made
      primarily asymmetric synapses onto dendritic spines and less commonly onto
      dendritic shafts. Most of the dendrites receiving MD synaptic input were
      immunoreactive for parvalbumin (ParV), whereas MD synapses onto dendrites labeled
      for calretinin or calbindin were less frequent. We also observed that some MD
      terminals were themselves immunoreactive for calcium-binding proteins, again more
      commonly for ParV. These results suggest that the MD exerts a dual influence on
      PFC pyramidal cells: direct inputs onto spines and an indirect influence mediated
      via synapses onto each subclass of interneurons. The apparent preferential input
      to ParV cells endows MD afferents with a strong indirect inhibitory influence on
      pyramidal neuron activity by virtue of ParV cell synapses onto soma, proximal
      dendrites, and axon initial segments.

PMID- 16082677
TI  - Localization of calcitonin receptor-like receptor and receptor activity modifying
      protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the
      rat.
AB  - Calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1
      (RAMP1) comprise a receptor for calcitonin gene related peptide (CGRP) and
      intermedin. Although CGRP is widely expressed in the nervous system, less is
      known about the localization of CLR and RAMP1. To localize these proteins, we
      raised antibodies to CLR and RAMP1. Antibodies specifically interacted with CLR
      and RAMP1 in HEK cells coexpressing rat CLR and RAMP1, determined by Western
      blotting and immunofluorescence. Fluorescent CGRP specifically bound to the
      surface of these cells and CGRP, CLR, and RAMP1 internalized into the same
      endosomes. CLR was prominently localized in nerve fibers of the myenteric and
      submucosal plexuses, muscularis externa and lamina propria of the
      gastrointestinal tract, and in the dorsal horn of the spinal cord of rats. CLR
      was detected at low levels in the soma of enteric, dorsal root ganglia (DRG), and
      spinal neurons. RAMP1 was also localized to enteric and DRG neurons and the
      dorsal horn. CLR and RAMP1 were detected in perivascular nerves and arterial
      smooth muscle. Nerve fibers containing CGRP and intermedin were closely
      associated with CLR fibers in the gastrointestinal tract and dorsal horn, and
      CGRP and CLR colocalized in DRG neurons. Thus, CLR and RAMP1 may mediate the
      effects of CGRP and intermedin in the nervous system. However, mRNA encoding
      RAMP2 and RAMP3 was also detected in the gastrointestinal tract, DRG, and dorsal
      horn, suggesting that CLR may associate with other RAMPs in these tissues to form
      a receptor for additional peptides such as adrenomedullin.

PMID- 16082678
TI  - Feasibility and safety of transradial artery approach for selective cerebral
      angiography.
AB  - The transradial artery (TRA) approach is a conventional means of diagnostic
      cardiac catheterization and catheter-based coronary intervention. However, to our
      knowledge, the safety and feasibility of cerebrovascular angiographic studies
      using the TRA approach for patients with brain ischemia has not been reported.
      This study investigated whether the TRA approach using 6 Fr Kimny guiding
      catheter for both extracranial and intracranial angiographies is safe and
      effective for patients with a history of stroke, transient ischemic attack, or
      significant carotid stenosis. From February 2003 to June 2004, a total of 46
      consecutive patients with an age range from 50 to 83 years were enrolled into the
      study. The retrograde engagement technique that involved lopping the guiding
      catheter was utilized. Outpatient carotid angiography was performed in 40% of the
      study patients. The overall procedural success (defined as completely evaluating
      both carotid and vertebral arteries and intracranial vessels) was 93.5% (n = 43)
      using the Kimny guiding catheter. Significant cerebrovascular stenosis (> 50%),
      including carotid artery in 52.2% (n = 24), vertebral artery in 15.2% (n = 7),
      and intracranial major artery in 15.2% (n = 7), was found in 82.6% of the
      patients. Notably, 17 (37.0%) of these patients with severe carotid stenosis (>
      or = 70%) required staged carotid stenting. Concomitant vertebral artery stenting
      was performed in four (8.7%) patients because of severe stenosis (> or = 70%) of
      these vessels. Two patients experienced transient dizziness (duration < 30 min)
      following the procedure. TRA approach for selective cerebral angiography is safe
      and feasible in patients with a history of brain ischemia.

PMID- 16082679
TI  - Ipsilateral cortical connections of motor, premotor, frontal eye, and posterior
      parietal fields in a prosimian primate, Otolemur garnetti.
AB  - The ipsilateral connections of motor areas of galagos were determined by
      injecting tracers into primary motor cortex (M1), dorsal premotor area (PMD),
      ventral premotor area (PMV), supplementary motor area (SMA), and frontal eye
      field (FEF). Other injections were placed in frontal cortex and in posterior
      parietal cortex to define the connections of motor areas further. Intracortical
      microstimulation was used to identify injection sites and map motor areas in the
      same cases. The major connections of M1 were with premotor cortex, SMA, cingulate
      motor cortex, somatosensory areas 3a and 1, and the rostral half of posterior
      parietal cortex. Less dense connections were with the second (S2) and parietal
      ventral (PV) somatosensory areas. Injections in PMD labeled neurons across a
      mediolateral belt of posterior parietal cortex extending from the medial wall to
      lateral to the intraparietal sulcus. Other inputs came from SMA, M1, PMV, and
      adjoining frontal cortex. PMV injections labeled neurons across a large zone of
      posterior parietal cortex, overlapping the region projecting to PMD but centered
      more laterally. Other connections were with M1, PMD, and frontal cortex and
      sparsely with somatosensory areas 3a, 1-2, S2, and PV. SMA connections were with
      medial posterior parietal cortex, cingulate motor cortex, PMD, and PMV. An FEF
      injection labeled neurons in the intraparietal sulcus. Injections in posterior
      parietal cortex revealed that the rostral half receives somatosensory inputs,
      whereas the caudal half receives visual inputs. Thus, posterior parietal cortex
      links visual and somatosensory areas with motor fields of frontal cortex.

PMID- 16082680
TI  - A compensatory subpopulation of motor neurons in a mouse model of amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis is a fatal paralytic disease that targets motor
      neurons, leading to motor neuron death and widespread denervation atrophy of
      muscle. Previous electrophysiological data have shown that some motor axon
      branches attempt to compensate for loss of innervation, resulting in enlarged
      axonal arbors. Recent histological assays have shown that during the course of
      the disease some axonal branches die back. We thus asked whether the two types of
      behavior, die-back and compensatory growth, occur in different branches of single
      neurons or, alternatively, whether entire motor units are of one type or the
      other. We used high-resolution in vivo imaging in the G93A SOD1 mouse model, bred
      to express transgenic yellow fluorescent protein in all or subsets of motor
      neurons. Time-lapse imaging showed that degenerative axon branches are easily
      distinguished from those undergoing compensatory reinnervation, showing
      fragmentation of terminal branches but sparing of the more proximal axon.
      Reconstruction of entire motor units showed that some were abnormally large.
      Surprisingly, these large motor units contained few if any degenerating synapses.
      Some small motor units, however, no longer possessed any neuromuscular contacts
      at all, giving the appearance of "winter trees." Thus, degenerative versus
      regenerative changes are largely confined to distinct populations of neurons
      within the same motor pool. Identification of factors that protect "compensatory"
      motor neurons from degenerative changes may provide new targets for therapeutic
      intervention.

PMID- 16082681
TI  - Pre- and postsynaptic localization of the 5-HT7 receptor in rat dorsal spinal
      cord: immunocytochemical evidence.
AB  - Several lines of evidence indicate that 5-HT7 receptors are involved in pain
      control at the level of the spinal cord, although their mechanism of action is
      poorly understood. To provide a morphological basis for understanding the action
      of 5-HT on this receptor, we performed an immunocytochemical study of 5-HT7
      receptor distribution at the lumbar level. 5-HT7 immunolabelling is localized
      mainly in the two superficial laminae of the dorsal horn and in small and medium
      sized dorsal root ganglion cells, which is consistent with a predominant role in
      nociception. In addition, moderate labelling is found in the lumbar dorsolateral
      nucleus (Onuf's nucleus), suggesting involvement in the control of pelvic floor
      muscles. Electron microscopic examination of the dorsal horn revealed three main
      localizations: 1) a postsynaptic localization on peptidergic cell bodies in
      laminae I-III and in numerous dendrites; 2) a presynaptic localization on
      unmyelinated and thin myelinated peptidergic fibers (two types of axon terminals
      are observed, large ones, presumably of primary afferent origin, and smaller ones
      partially from intrinsic cells; this presynaptic labelling represents 60% and 22%
      of total labelling in laminae I and II, respectively); and 3) 16.9% of labelling
      in lamina I and 19.8% in lamina II are observed in astrocytes. Labeled astrocytes
      are either intermingled with neuronal elements or make astrocytic "feet" on blood
      vessels. In dendrites, the labelling is localized on synaptic differentiations,
      suggesting that 5-HT may act synaptically on the 5-HT7 receptor. This
      localization is compared with other 5-HT receptor localizations, and their
      physiological consequences are discussed.

PMID- 16082682
TI  - Phase diagram of electrostricted H2O at surfaces of electrodes at 273-373 K:
      electric critical point of water.
AB  - The equation of state of an open system containing water in an electric field of
      strength E greater than 108 V m-1 leads to a phase diagram with two-phase and
      single-phase regions in the Pi,E,T coordinates (=electrostriction pressure). The
      phases differ by their degree of orientation of H2O molecules in the field. The
      phase transition is discontinuous with respect to E. The calculation shows that
      the discontinuity vanishes at the critical point: Pi(c) approximately 0.2 GPa, Ec
      approximately 109 V m-1 and below 313 K. The thermal effect of the transition is
      calculated and compared with an experiment at the Hg/aqueous electrolyte
      interface found in the literature.

PMID- 16082683
TI  - Transcatheter closure of the patent arterial duct using the Flipper coil in a
      premature infant weighing 1,400 g: a case report.
AB  - A symptomatic 1,400 g premature triplet underwent successful transcatheter coil
      embolization of patent arterial duct using the umbilical artery. One 3 mm x 3 cm
      Flipper coil was used with no angiographic residual shunt. To the best of our
      knowledge, this is one of the smallest preterm infants to undergo this
      transcatheter procedure.

PMID- 16082684
TI  - Randomized study of the safety and clinical utility of rotational vs. standard
      coronary angiography using a flat-panel detector.
AB  - The purpose of this study was to test the hypothesis that rotational angiography
      improves patient safety while maintaining diagnostic accuracy for patients
      undergoing coronary angiography. Despite advances in angiographic technique,
      patients remain at risk for complications of coronary angiography, including
      contrast-induced nephropathy and radiation exposure. Technology has been
      developed to perform coronary angiography with active rotation of the imaging
      system that may reduce the quantity of contrast and radiation to which the
      patient is exposed. Fifty patients undergoing diagnostic cardiac catheterization
      were randomized to either standard vs. rotational angiography of the coronary
      arteries using a prespecified protocol with a flat-panel single-plane imaging
      system. We measured the quantity of radiographic contrast utilized and radiation
      exposure. Using an intention-to-treat analysis, there was a 40% reduction (24 +/-
      5 vs. 40 +/- 10 ml; P < 0.0001) in contrast utilization in the rotational group
      compared to the standard group. Neither radiation exposure (35 +/- 14 vs. 30 +/-
      20 Gycm(2); P = 0.35), fluoroscopic time (44 +/- 33 vs. 44 +/- 40 sec; P = 0.99),
      nor procedure time (249 +/- 137 vs. 214 +/- 79 sec; P = 0.26) differed, although
      significant intraoperator variability was noted for both standard and rotational
      angiography. The radiation exposure using this flat-panel system is significantly
      lower than prior reports that used an image intensifier system. Rotational
      coronary angiography has the potential to improve patient safety by markedly
      reducing radiographic contrast exposure while maintaining comparable diagnostic
      accuracy, radiation exposure, and procedure time compared to standard coronary
      angiography.

PMID- 16082685
TI  - Double-inversion technique for coronary angiography viewing in dextrocardia.
AB  - This report describes a simple angiographic viewing rule for coronary angiography
      in patients of dextrocardia with obstructive coronary artery disease, which could
      correct the unfamiliar angulated pictures of the coronary tree in dextrocardia
      into the familiar conventional angiographic pictures of a normally located heart
      and its associated ease of interpretation.

PMID- 16082686
TI  - Initial clinical experience with intracardiac echocardiography in guiding
      transcatheter closure of perimembranous ventricular septal defects: feasibility
      and comparison with transesophageal echocardiography.
AB  - Over the last several years, intracardiac echocardiography (ICE) has been
      employed successfully in guiding transcatheter device closure of a secundum
      atrial septal defect (ASD) or patent foramen ovale (PFO). Nothing is known
      regarding the use of ICE to guide catheter device closure of a perimembranous
      ventricular septal defect (PMVSD). Twelve patients (seven female/five male) who
      had a PMVSD (among them, three patients with associated atrial communications:
      two with an ASD and one with a PFO) underwent attempts at transcatheter device
      closure using the Amplatzer membranous VSD device of their defects, using
      sequential transesophageal echocardiography (TEE) and ICE guidance with general
      endotracheal anesthesia (five patients) and using ICE alone with conscious
      sedation (seven patients). The mean age of patients was 16.9 +/- 3.7, and their
      mean weight was 42.4 +/- 6.6. Their mean left ventricular end-diastolic dimension
      preclosure was 45.7 +/- 2.5. The Qp/Qs ratio ranged from 1.0 to 1.8:1. During the
      procedure, the ICE catheter was positioned in the right atrium (RA) in all 12
      patients and the ICE catheter was advanced to the left atrium to obtain a view of
      the ventricular septum in 3. Both TEE and ICE provided similar anatomical views
      of the position of the PMVSD. Furthermore, the relationship of the defect to the
      aortic valve and tricuspid valves, the measured size of defect, and the guidance
      of various stages of device deployment were comparable by TEE and ICE. There were
      no complications encountered during or after closure. We conclude that ICE
      provides unique images of the PMVSD and measurements similar to those obtained by
      TEE. ICE potentially could replace TEE in most patients as a guiding imaging tool
      for PMVSD device closure, thus eliminating the need for general endotracheal
      anesthesia.

PMID- 16082687
TI  - Controlled myocardial infarction induced by intracoronary injection of n-butyl
      cyanoacrylatein dogs: a feasibility study.
AB  - Concentrated ethanol has been used to induce controlled myocardial infarct in
      patients with hypertrophic obstructive cardiomyopathy. We report the acute and
      early follow-up results of an alternative agent, n-butyl cyanoacrylate (n-BCA)
      glue, in a dog model. In 11 mongrel dogs, we injected n-BCA into different
      branches of the left anterior descending artery. Biplane left ventriculogram and
      coronary angiogram were performed before and after injection. In the surviving
      animals, we performed programmed stimulation (PS) to test for inducible
      ventricular tachycardia (VT) 48 days later. Following euthanasia, the removed
      hearts were studied with computer tomography (CT) and gross and histologic
      examination. Three dogs were lost before injection. Four dogs died within 2 hr to
      4 days, and four animals survived 48 days. Accidental embolization of n-BCA into
      nontarget vessels was documented in four subjects. In the n-BCA-injected animals,
      homogeneous circumscribed scar was demonstrated by CT and histology. The glue was
      confined strictly to the tributary of the injected vessel, infiltrating
      arterioles of 14 mum. There was intense granulomatous reaction (GR) in the vessel
      wall and in the surrounding myocardium. Remote areas were unaffected. Monomorphic
      VT was not inducible with PS. We report a feasibility study of n-BCA injection to
      selected coronary arteries of dogs to cause controlled myocardial infarction. We
      demonstrated that the glue does not escape from the target artery through
      capillaries or small collateral vessels and thus produces a sharply demarcated
      and homogeneous scar, which is confined strictly to the supply zone of the
      injected vessel. Improvement of the delivery system is necessary to eliminate
      inadvertent embolization. Long-term follow-up is needed to study the GR induced
      by n-BCA.

PMID- 16082688
TI  - No support for association between the dopamine transporter (DAT1) gene and ADHD.
AB  - Several groups have reported an association between the 10-repeat allele of a
      dopamine transporter (DAT1) 3'UTR VNTR variant and ADHD but the finding has not
      been universally observed. An association between DAT1 genotype and stimulant
      medication response has also been reported although again there are conflicting
      data. We tested the DAT1 3'VNTR and three SNPs in the putative promoter region of
      DAT1 for association with ADHD in 263 parent-proband trios. Analyses of
      genotypes, alleles, and haplotypes were performed using family-based association
      methods. Case-control analysis of the VNTR in 263 cases and 287 controls was also
      conducted. In addition, we tested for association between the VNTR marker and
      stimulant medication response. Comparing allele 10 versus all other alleles
      combined, no significant association was found with ADHD, using FBAT analysis
      (chi2 = 0.1 (df 1), P = 0.9, (odds ratio (OR) = 1.0, 95% CI 0.8-1.2), and case
      control analysis (chi2 = 0.12 (df 2), P = 0.91). No evidence of association with
      any of the SNPs in the promoter region was found. Haplotype analysis was also non
      significant (chi2 = 3.93, (df 9) global P = 0.85). Finally, no association was
      found between the DAT 1 VNTR and response to stimulant medication (chi2 = 1.63
      (df 3) P = 0.65). We conclude that the 3' VNTR and three additional promoter
      variants in DAT1 do not appear to be associated with ADHD, or response to
      stimulant mediation in our sample.

PMID- 16082689
TI  - Teenage asthma after severe early childhood wheezing: an 11-year prospective
      follow-up.
AB  - The role of factors related to early wheezing and their associations with
      subsequent development of asthma are controversial. We reevaluated 81 children
      who had been prospectively followed up since hospitalization for wheezing at less
      than 2 years of age. The baseline data on characteristics of the children, family
      related factors, and viral causes of wheezing were collected on entry into the
      study. At the median age of 12.3 years, current symptoms suggestive of asthma and
      allergy were recorded. As part of the clinical examination, an outdoor exercise
      challenge test and skin prick tests to common inhalant allergens were performed.
      Asthma, as indicated by current inhaled anti-inflammatory medication or repeated
      wheezing and positive result in the challenge test, was present in 32 (40%)
      children, and 90% of them were sensitized to at least one allergen. Early asthma
      predictive factors were atopic dermatitis (odds ratio (OR), 3.5; 95% confidence
      interval (CI), 1.2-10.1) and the presence of specific IgE to inhalant allergens
      (OR, 11.3; 95% CI, 1.9-67.6). Respiratory syncytial virus (RSV) identification
      during wheezing in infancy was relatively rare (20%) among later asthmatics
      compared with other or no viral identification (52%) or rhinovirus identification
      (58%). Since the prevalence of childhood asthma in our area is 4.0-5.0%, we
      conclude that the increased risk of asthma persists until the teenage years after
      hospitalization for wheezing in infancy. The risk was about 5-fold after
      respiratory syncytial virus-induced wheezing, and more than 10-fold after
      rhinovirus-induced wheezing in the present study.

PMID- 16082690
TI  - Family-based association study of serotonin transporter gene polymorphisms in
      attention deficit hyperactivity disorder: no evidence for association in UK and
      Taiwanese samples.
AB  - Five independent studies have reported associations between serotonin transporter
      gene (5-HTT) polymorphisms and attention deficit hyperactivity disorder (ADHD).
      Four studies found evidence for association between the long-allele of a 44-base
      pair insertion/deletion polymorphism (5-HTTLPR), one of the studies found
      association to a variable number tandem repeat within intron 2, another to the T
      allele of a single base pair substitution in the 3'-untranslated regions and
      another reported preferential transmission of a haplotype of the three markers
      (long-allele/10-repeat-allele/T-allele). One further study found no evidence for
      these associations. We investigated the association of these three markers in two
      samples of ADHD patients from the United Kingdom (n = 197) and Taiwan (n = 212),
      using within-family tests of association. No association was found between any of
      the three markers in either of the two populations. Although we found some
      evidence for the preferential transmission of a rare haplotype (long-allele/9
      repeat-allele/T-allele; chi2 = 4.5, P = 0.034), we concluded that this most
      likely occurred by chance factors alone.

PMID- 16082691
TI  - Pulmonary interstitial glycogenosis in identical twins.
AB  - We present the clinical, radiological, and pathological findings of open lung
      biopsies from monozygotic prematurely born male twins with respiratory distress
      at ages 6 and 8 weeks postnatally. Radiological examination showed a reticular
      nodular interstitial pattern on chest radiography. High-resolution computed
      tomography (HRCT) revealed ground-glass opacification and thickened interstitial
      septae in both infants. Lung biopsies showed a similar histology. There was
      diffuse interstitial thickening of the alveolar septa by mesenchymal cells,
      without prominent hyperplasia of type 2 pneumocytes, and without airspace
      exudates. Sections were periodic acid-Schiff (PAS)-positive within the cytoplasm
      of interstitial cells, indicating the presence of glycogen. Thus the diagnosis of
      pulmonary interstitial glycogenosis was made. Both infants were treated with
      glucocorticoids and had a favorable outcome. We speculate that pulmonary
      interstitial glycogenosis could be a histopathological form of chronic lung
      disease (CLD) of infancy.

PMID- 16082692
TI  - Neuregulin-1 polymorphism in late onset Alzheimer's disease families with
      psychoses.
AB  - Probands with late onset Alzheimer's disease (LOAD) exhibit positive symptoms of
      psychosis, 30-60% of the time. Positive symptoms of psychosis have been shown to
      appear prior to the onset of dementia to be accompanied by greater cognitive
      deficits, and to predict a more rapid decline. A study of the distribution of AD
      with psychosis (ADP) in families from the NIMH Alzheimer's Disease Genetic
      Initiative sample indicates that the trait is heritable, and linkage studies of
      multiplex ADP families have found suggestive peaks on 2p, 6q, 8p, and 21q. A
      genome scan of idiopathic psychosis, schizophrenia, in the Icelandic population
      identified a risk haplotype within the 5' region of neuregulin-1 (NRG1) on 8p12.
      Associations with NRG1 SNPs have also been found in other schizophrenia
      populations from Scotland, Ireland, and China. Here, we report results
      demonstrating a significant linkage peak for ADP on 8p12 in the NIMH AD dataset,
      encompassing the NRG1 region. We also demonstrate that there is a significant
      association with a NRG1 SNP (single nucleotide polymorphism), rs392499, with ADP,
      chi2 = 7.0, P = 0.008. This same SNP is part of a 3-SNP haplotype preferentially
      transmitted to individuals with this phenotype. Our results suggest that NRG1
      plays a role in increasing the genetic risk to positive symptoms of psychosis in
      a proportion of LOAD families.

PMID- 16082693
TI  - Sequence variation in the 3'-untranslated region of the dopamine transporter gene
      and attention-deficit hyperactivity disorder (ADHD).
AB  - The dopamine transporter gene (DAT1) has been reported to be associated with
      attention-deficit hyperactivity disorder (ADHD) in a number of studies [Cook et
      al. (1995): Am J Human Genet 56(4):9993-998; Gill et al. (1997): Mol Psychiatry
      2(4):311-313; Waldman et al. (1998): Am J Human Genet 63(6):1767-1776; Barr et
      al. (2001): Biol Psychiatry 49(4):333-339; Curran et al. (2001): Mol Psychiatry
      6(4):425-428; Chen et al. (2003): Mol Psychiatry 8(4):393-396]. Specifically, the
      10-repeat allele of the 40-bp variable number of tandem repeats (VNTR)
      polymorphism located in the 3' untranslated region (UTR) of the gene has been
      found to be associated with ADHD. There is evidence from in vitro studies
      indicating that variability in the repeat number, and sequence variation in the
      3'-UTR of the DAT1 gene may influence the level of the dopamine transporter
      protein [Fuke et al. (2001): Pharmacogenomics J 1(2):152-156; Miller and Madras
      (2002): Mol Psychiatry 7(1):44-55]. In this study, we investigated whether DNA
      variation in the DAT1 3'UTR contributed to ADHD by genotyping DNA variants around
      the VNTR region in a sample of 178 ADHD families. These included a MspI
      polymorphism (rs27072), a DraI DNA change (T/C) reported to influence DAT1
      expression levels, and a BstUI polymorphism (rs3863145) in addition to the VNTR.
      We also screened the VNTR region by direct resequencing to determine if there was
      sequence variation within the repeat units that could account for the
      association. Our results indicate that DAT1 is associated with ADHD in our sample
      but not with alleles of the VNTR polymorphism. We did not find any variation in
      the sequence for either the 10- or 9-repeat alleles in the probands screened nor
      did we observe the reported DraI (T/C) variation. Our results therefore refute
      the possibility of the reported DraI variation or alleles of the VNTR as the
      functional variants contributing to the disorder.

PMID- 16082694
TI  - Analysis of the SREBF2 gene as a genetic risk factor for vascular dementia.
AB  - A case-control study was performed to examine the association between vascular
      dementia and the polymorphisms of the human gene encoding sterol regulatory
      element binding protein-2 (SREBF2) that regulates cholesterol metabolism. The 16
      genetic variants of SREBF2 were identified in 24 Koreans, and 5 out of 16
      variants were genotyped in 207 vascular dementia patients and 207 control
      subjects. Significant association with vascular dementia was shown in 34995G/T
      with the GT genotype (odds ratio [OR] = 1.57; 95% CI = 1.04-2.37; P < 0.05) and
      the GG genotype (OR = 0.65; 95% CI = 0.44-0.96; P < 0.05). The CGC, the most
      common haplotype combined with three SNPs, 24489C/T, 34995G/T, and 68891C/T, was
      associated with the disease (OR = 0.72; 95% CI = 0.53-0.97; P < 0.05), and the
      individuals with the CGC might be less susceptible to vascular dementia than
      those carrying any haplotype including at least one minor allele. This study
      implied that the variants of SREBF2 might be genetic factors involved in the
      pathogenesis of vascular dementia.

PMID- 16082695
TI  - Preparation of thermosensitive microgels via suspension polymerization using
      different temperature protocols.
AB  - A thermosensitive and biodegradable microgel for protein drug release was
      synthesized from a thermosensitive macromer via inverse suspension
      polymerization. Preparation was made under a constant temperature or under
      variable temperatures. In the latter protocol, dispersion was performed at a low
      temperature below lower critical solution temperature of the macromer aqueous
      solution and polymerization was performed at a high temperature above lower
      critical solution temperature. According to the experiments, the constant
      temperature method was not suitable for preparation of microgels when the
      macromer concentration was high, because early physical gelation at the
      preparation temperature seriously influenced formation of dispersed droplets. If
      the macromer concentration was low, both temperature protocols resulted in
      spherical hydrogel microparticles, but the properties of the resulting microgels
      were different to a certain degree. In both cases, the model protein bovine serum
      albumin was loaded into microgels by a postfabrication encapsulation technique,
      which takes advantage of the microgels' negative thermosensitivity. The results
      demonstrate that, in microgel preparation, the variable-temperature protocol is
      useful in suspension polymerization of negatively thermosensitive macromers at a
      wide rage of monomer concentrations.

PMID- 16082696
TI  - Childhood diffuse panbronchiolitis: a case report.
AB  - Diffuse panbronchiolitis (DPB) is a chronic, potentially life-threatening lower
      respiratory tract disease that is particularly common in Japanese people. If left
      untreated, it progresses to bronchiectasis, respiratory failure, and death. Lack
      of familiarity with DPB in the non-Far East may result in a failure to correctly
      diagnose and treat this disorder. We describe a child with DPB. We suggest that
      DPB is a sinopulmonary disease that is not exclusive to the Asian population and
      to adults. Its clinical and radiological features should be better known by
      pediatric pulmonary physicians.

PMID- 16082697
TI  - Randomized, placebo-controlled trial of albuterol and epinephrine at equipotent
      beta-2 agonist doses in acute bronchiolitis.
AB  - Our objective was to determine if nebulized racemic epinephrine is more
      efficacious than nebulized albuterol or saline placebo in the treatment of
      bronchiolitis in the outpatient setting when dosing is equivalent in terms of
      beta-2 agonist potency. Sixty-five patients between ages 6 weeks and 24 months
      with a diagnosis of bronchiolitis, defined as first-time wheezing, upper
      respiratory symptoms and/or fever, and a Respiratory Distress Assessment
      Instrument score of at least 4, were randomized to receive 5 mg nebulized
      albuterol, 5 mg nebulized racemic epinephrine, or an equivalent volume of placebo
      at 0, 30, and 60 min. The primary outcome measure was need for hospital admission
      or home oxygen. Secondary outcome measures were changes in clinical scores and
      oxygen saturations. There were no significant statistical differences between
      groups in terms of need for hospital admission or outpatient management with home
      oxygen therapy. There were no differences between groups in terms of changes in
      clinical scores or oxygen saturations. Racemic epinephrine and albuterol at
      equivalent doses had no effect on the need for hospitalization or supplemental
      oxygen in bronchiolitis in the outpatient setting compared to nebulized saline
      placebo, though this study may have missed less dramatic clinical effects due to
      small sample size.

PMID- 16082698
TI  - Family-based association study of the serotonin transporter gene polymorphisms in
      Korean ADHD trios.
AB  - The dopamine (DA) system has been implicated in attention deficit hyperactivity
      disorder (ADHD) based on pharmacologic evidence. Because of an interaction
      between the serotonin (5-HT) and DA systems, the serotonin transporter gene
      (SLC6A4) has been considered as a candidate ADHD susceptibility gene. Two common
      polymorphisms, 5-HTTLPR and the intron 2 VNTR, have been studied for association
      in ADHD, with both positive (increased frequency of long allele of 5-HTTLPR and
      decreased frequency of 12 repeats of the intron 2 VNTR) and negative findings.
      However, there has not been an association study in an East Asian ADHD
      population. In this study, we examined the genotypes of these two polymorphisms
      in 126 Korean ADHD families and investigated linkage disequilibrium (LD) between
      SLC6A4 and ADHD, using the transmission disequilibrium test (TDT) and haplotype
      analysis. Additionally, association with quantitative measures of inattention,
      hyperactivity-impulsivity, and overall severity was tested using logistic
      regression and QTDT analysis. TDT of both polymorphisms and haplotype analysis
      failed to detect LD. However, after excluding ADHD NOS subtype, TDT revealed
      nominally significant LD between 5-HTTLPR and ADHD (chi2 = 4.9, P = 0.036). QTDT
      revealed positive association between 12 repeats of the intron 2 VNTR and
      attention (P = 0.031), but case-control and TDT logistic regression analyses were
      negative. These markers have low heterozygosity in the Korean population, which
      would be expected to reduce the power of association. This result suggests that
      future studies should include more polymorphic markers and subjects to thoroughly
      investigate a potential association between SLC6A4 and ADHD in the Korean
      population.

PMID- 16082699
TI  - In vitro study of drug loading on polymer-free oxide films of metallic implants.
AB  - Traditionally, a drug that is loaded onto a metallic surface has to use various
      polymer bondings as its platform. Unfortunately, polymer coatings on a metallic
      surface cause numerous problems after implantation, such as late thrombosis,
      inflammation, and restenosis. This research was conducted to investigate whether
      an oxide layer can be used as a polymer-free platform for drug loading,
      especially for cardiovascular stents. The interaction and loading of heparin onto
      different oxide films on 316LVM stainless steel wire was confirmed in vitro by
      experimental studies using linear voltammetry, electrochemical impedance
      spectroscopy, and electron spectroscopy for chemical analysis. The eluting of
      heparin from heparinized surface was studied by using high-performance liquid
      chromatography, and activated clotting time in addition to linear voltammetry and
      electron spectroscopy for chemical analysis analyses. Experimental results show
      that amorphous oxide could be a potential substitute for the polymer coating of
      drug-loaded stents for minimizing metallic corrosion, inflammation, late
      thrombosis, and restenosis.

PMID- 16082700
TI  - Pulmonary function and structure following mild preterm birth in lambs.
AB  - Our objective was to determine whether postnatal respiratory function, lung
      growth, and lung structure are affected by preterm birth which did not require
      neonatal respiratory support. Two groups of preterm (P) lambs were delivered 2
      weeks before term, at 133 days of gestational age (GA). Tissue was collected at
      term equivalent age (TEA, 147 days GA) in one P group and at 6 weeks post-TEA in
      the other. Tissue was also collected from control (C) lambs soon after term birth
      (TEA) and at 6 weeks post-TEA. Lung function was assessed at TEA and 6 weeks post
      TEA. Respiratory system compliance (Crs/kg BWT) was not different between P and C
      groups at TEA, but was higher (P = 0.02) in P lambs at 6 weeks post-TEA.
      Pulmonary resistance was 62% higher in P lambs than controls (P = 0.07) at TEA,
      and remained higher at 6 weeks post-TEA. Lung weights (wet and dry) were greater
      (P < 0.05) in preterm animals at both ages; when adjusted for body weight, only
      dry lung weight remained higher at 6 weeks post-TEA. Alveoli were more numerous
      (P = 0.05) and smaller (P = 0.05) in preterm lambs compared to controls at both
      ages. Alveolar septa were 33% thicker and the blood-air barrier was 26% thicker
      in P lambs than in controls at TEA, and remained thicker at 6 weeks post-TEA. In
      P lambs, the airway epithelium was thicker at TEA and 6 weeks post-TEA. At TEA,
      pulmonary tropoelastin expression was 27% lower in P lambs. At 6 weeks post-TEA,
      dry lung weight and lung protein content were approximately 50% greater in
      preterm lambs than in controls (P < 0.05), whereas lung DNA, elastin, and
      collagen contents were similar in the two groups. We conclude that mild preterm
      birth per se leads to both transient and persistent changes in lung development.
      Persistent increases in lung protein content and in the thickness of the airway
      epithelium, and a greater number of smaller alveolar, may alter later lung
      function.

PMID- 16082701
TI  - Transmission disequilibrium and haplotype analyses of the G72/G30 locus:
      suggestive linkage to schizophrenia in Palestinian Arabs living in the North of
      Israel.
AB  - Association of the G72/G30 locus with schizophrenia was recently reported in
      French Canadian, Russian, and Ashkenazi populations using case-control studies.
      In the present study we hypothesize the existence of a G72/G30 risk allele over
      transmitted to affected sibs in Palestinian Arab families. A total of 223
      Palestinian Arab families that included an affected offspring and parents were
      genotyped with 11 SNPs encompassing the G72/G30 genes. The families were
      recruited from three regions of Israel: 56 from the North (Afula), 136 from the
      central hill region (Bethlehem, Palestinian Authority), and 31 from the South
      (Beersheva). Individual SNP analyses disclosed a risk allele in SNP rs3916970 by
      both haplotype relative risk (HRR: chi(2) = 5.59, P = 0.018) and transmission
      disequilibrium test (TDT: chi(2) = 6.03, P = 0.014) in the Afula families. Follow
      up multilocus analysis using family-based association tests (FBAT: z = 2.197, P =
      0.028) exposed the adjacent haplotype. SNP rs3916970 is located about 8 kb from
      the linkage disequilibrium block that was reported to be associated with
      schizophrenia in Ashkenazi Jews. Excess of similar haplotypes of this region was
      observed in the Palestinian Arabs and the Ashkenazi patients. These data suggest
      a common risk factor for schizophrenia susceptibility in the G72/G30 locus among
      Ashkenazi Jews and Palestinian Arabs. The results strengthen previous reports on
      the role of this locus in the etiology of schizophrenia.

PMID- 16082702
TI  - DNA pooling analysis of ADHD and genes regulating vesicle release of
      neurotransmitters.
AB  - ADHD is one of the most prevalent, and heritable behavioural disorders in
      childhood. Genetic associations have been reported with polymorphic variants
      within or near to dopamine pathway genes. Recently snap-25 has also shown
      association with ADHD in several datasets. We therefore investigated other genes
      that produce proteins that interact with SNAP-25 in the mechanism of vesicular
      release of neurotransmitters at the synapse. A total of 106 SNPs were screened
      for minor allele frequency greater than 5% and 61 SNPs selected for analysis in
      DNA pools made up from an ADHD clinical sample of DSM-IV combined type probands
      (n = 180) and a control sample of 90 males and 90 females. Initial screening
      identified several SNPs that showed allele frequency differences of 5% or more.
      One SNP in the synaptophysin gene showed suggestive evidence of association
      following case-control and TDT analysis and warrants further investigation.

PMID- 16082703
TI  - Ring chromosome 4 in a patient with early onset type 2 diabetes, deafness, and
      developmental delay.
AB  - To date, most ring formations of chromosome 4 lose distal 4p and usually include
      the Wolf-Hirschhorn syndrome region [WHS]. We describe a case with r(4) in a girl
      who presented without features of WHS; she had mild developmental delay,
      deafness, short stature, obesity, and the onset of type 2 diabetes in
      adolescence, a distinctive phenotype. Although 4p was significantly deleted on
      Giemsa banding, the 4p junction was distal to the WHS and FGFR3 but proximal to
      the D4S3360 marker. The 4q breakpoint was close to the telomere. The phenotype
      appears different from previous patients with 4p- or r(4), which have had more
      extensive 4p deletion.

PMID- 16082704
TI  - Proteomic analysis of protein adsorption: serum amyloid P adsorbs to materials
      and promotes leukocyte adhesion.
AB  - Serum and plasma protein adsorption on materials was analyzed using gel
      electrophoresis and ion trap mass spectrometry. Following incubation of
      polypropylene, polyethylene terephthalate (PET), or polydimethylsiloxane (PDMS)
      with 5% serum for longer than 4 h, we found unexpectedly high amounts of the
      pentraxin serum amyloid P. It was previously shown that serum amyloid P is
      constitutively expressed in humans, functions as an opsonin, and interacts with
      the Fcgamma receptors on leukocytes. We demonstrate that serum amyloid P adsorbed
      to tissue culture polystyrene, PDMS, and PET promotes the adhesion of
      granulocytes and monocytes in the presence of calcium. The methods developed for
      these studies may be useful for the large-scale study of protein adsorption and
      do not rely on radiolabeling or the availability of antibodies.

PMID- 16082705
TI  - Patient with a non-mosaic isodicentric Yp and mild developmental delay.

PMID- 16082706
TI  - A patient with mosaic partial trisomy 18 resulting from dicentric chromosome
      breakage.
AB  - We present a patient with minor dysmorphic features and a mosaic karyotype with
      two different abnormal cell lines, both involving abnormalities of chromosome 18.
      Twenty percent of cells studied (4/20) had 46 chromosomes with a large derivative
      pseudoisodicentric chromosome 18. This chromosome was deleted for 18pter and
      duplicated for part of proximal 18p (18p11.2 based on fluorescence in situ
      hybridization (FISH) studies and all of 18q. The two copies of portions of
      chromosome 18 were fused in an inverted fashion (duplicated for 18qter->18p11.3).
      The smaller der(18) was present in 80% of cells studied (16/20) and had a normal
      q-arm, while the p-arm was missing the subtelomere region but had duplication of
      a part of 18p. FISH studies showed that the larger derivative 18 contained the
      18q subtelomere at each end, but the 18p subtelomere was absent, consistent with
      fusion of two regions within 18p resulting in deletion of the subtelomeric
      regions. The smaller der(18) was also missing the 18p subtelomere (with normal
      18q as expected). Further testing with BAC clones mapping within 18p11.2 showed
      that these sequences were duplicated and inverted in both of the der(18)s. These
      findings lead us to hypothesize that the smaller der(18) was derived from the
      larger, dicentric 18 following anaphase bridge formation, with breakage distal to
      the duplicated segment.

PMID- 16082707
TI  - Geneticists' views on science policy formation and public outreach.
AB  - Though much research about the public's views of scientists, genetic research and
      its moral, ethical, and social implications exists, little has been done to
      investigate how scientists view their own role(s) in public discussions and
      policy formation related to genetic research and technologies. We interviewed 20
      academic geneticists in the United States about their perceptions of the roles
      they and others (e.g., professional societies, the public, ethicists, and elected
      officials) do and should play in the formation of science policy, the
      communication of science to the public, and the public discussions of moral and
      ethical issues raised by scientific advances. The participants in our study
      thought that scientists should be more actively involved in public outreach and
      science policy formation, but frequently they felt ill-equipped and unsupported
      by their peers and institutions to pursue these activities. Furthermore, many
      were skeptical of or did not trust elected officials--who they consider
      uninformed about the issues and too driven by political agendas--to formulate
      sound science policy. They do, however, have faith in the ability of scientific
      societies to influence policy effectively, and some thought that societies should
      play a larger role, both in science policy and as a liaison between scientists
      and the public. Finally, participants offered suggestions for increasing the
      involvement and influence of scientists in science-policy formation and public
      discourse.

PMID- 16082708
TI  - Relationship between FEV1 and peak oxygen uptake in children with cystic
      fibrosis.
AB  - Cross-sectional data do not truly convey the manner in which declining lung
      function affects peak oxygen uptake (peak VO2) within a given patient with cystic
      fibrosis. We hypothesized that there would be a concomitant decline in peak VO2
      with FEV1 over time. Twenty-eight children aged 8-17 years with cystic fibrosis
      performed annual ergometer tests over a 5-year period to determine peak VO2 and
      within-patient predictors of change in peak VO2. Analysis was done using a mixed
      effects model. During the study period, the annual decline in FEV1 averaged 2.7%
      of the predicted value per year. Peak VO2 fell during the observation period in
      70% of patients, with an average annualized decline of 1.9 ml x min(-1) x kg(-1).
      This rate of decline was greater in older children in contrast to younger
      children, some of whom had an improvement in peak VO2 over the first few years,
      consistent with growth and maturation. There was no difference in this rate of
      decline between sexes, but girls started with a slightly lower peak VO2 (37.9 vs.
      45.1 ml x min(-1) x kg(-1)). In patients with FEV1 <80% predicted, declining FEV1
      was highly correlated with falling peak VO2, whereas it remained stable over 4-5
      years in patients whose FEV1 was >80% predicted and remained in that range. We
      conclude that peak VO2 remains stable or rises slightly over time in younger
      patients, while it shows a downward trend in older children with CF, particularly
      once FEV1 falls below 80% predicted. Peak VO2 is correlated with FEV1 during
      childhood in patients with cystic fibrosis, and both FEV1 and age influence peak
      VO2.

PMID- 16082709
TI  - Failure to confirm association between RGS4 haplotypes and schizophrenia in
      Caucasians.
AB  - The regulator of G-protein signaling (RGS) and RGS-like proteins are a diverse
      family of over 30 molecules that function as GTPase activating proteins for
      Galpha subunits of the Gq and Gi families of heterotrimeric guanine nucleotide
      binding proteins (G proteins). By accelerating GTPase activity, RGS proteins
      drive G proteins into their inactive GDP-bound forms. G-protein coupled dopamine,
      metabotropic glutamate, and other neurotransmitter receptors can be modulated by
      RGS4, the predominant form in brain. The recent finding of decreased RGS4 mRNA
      expression in post-mortem brains from schizophrenic patients, coupled with the
      map position of RGS4 to a region previously linked to schizophrenia, as well as
      other biological data, prompted the investigation of the gene as a disease
      candidate. Multiple family-based and case-control association studies have been
      conducted, with modest and conflicting support for particular single nucleotide
      polymorphism (SNP) markers and SNP marker haplotypes. The present case-control
      analysis of 568 patients and 689 controls, one of the largest single studies to
      date, failed to confirm support for association of particular RGS4 SNP alleles,
      or for association of any particular four, three, or two SNP haplotype.

PMID- 16082710
TI  - Small-volume rapid-mix device for subsecond kinetic analysis in flow cytometry.
AB  - BACKGROUND: Rapid-mix flow cytometry has emerged as a powerful tool for
      mechanistic analysis of ligand binding, cell response, and molecular assembly.
      Although progress has come from improving sample delivery capabilities, little
      attention has been paid to the volumetric requirements associated with precious
      biological reagents. METHODS: By using programmable syringes, valves, and other
      fluidic components, we created a modular, precisely regulated rapid-mix device
      for the delivery of small-volume samples to the flow cytometer. The device was
      tested using a bead-based assay in which the binding kinetics between native
      biotin and fluorescein biotin-bearing beads were characterized. RESULTS: Bead
      suspensions and reagents paired in 35- to 45-microl aliquots were efficiently
      mixed by the device and delivered to the flow cytometer. Kinetic data associated
      with the fluorescein biotin beads were analyzed and used to calibrate the
      performance characteristics of the device in terms of sample delivery and mixing
      efficiency. CONCLUSION: The rapid-mix device is capable of detecting subsecond
      kinetics of biological reactions using microliter volume of samples. Dimensions
      of the device have been minimized, and the quantitative aspects of sample
      delivery and analysis have been optimized. Further, the modular design has been
      optimized for adaptation to a variety of experimental protocols.

PMID- 16082711
TI  - DNA labeling in living cells.
AB  - BACKGROUND: Live cell fluorescence microscopy experiments often require
      visualization of the nucleus and the chromatin to determine the nuclear
      morphology or the localization of nuclear compartments. METHODS: We compared five
      different DNA dyes, TOPRO-3, TOTO-3, propidium iodide, Hoechst 33258, and DRAQ5,
      to test their usefulness in live cell experiments with continuous imaging and
      photobleaching in widefield epifluorescence and confocal laser scanning
      microscopy. In addition, we compared the DNA stainings with fluorescent histones
      as an independent fluorescent label to mark chromatin. RESULTS: From the dyes
      tested, only Hoechst and DRAQ5 could be used to stain DNA in living cells.
      However, DRAQ5 had several advantages, namely low photobleaching, labeling of the
      chromatin compartments comparable to that of H2B-GFP fusion proteins, and deep
      red excitation/emission compatible with available genetically encoded fluorescent
      proteins such as C/G/YFP or mRFP. CONCLUSIONS: The DNA dye DRAQ5 is well suited
      for chromatin visualization in living cells and can easily be combined with other
      fluorophores with blue to orange emission.

PMID- 16082712
TI  - Cytomics and location proteomics: automated interpretation of subcellular
      patterns in fluorescence microscope images.

PMID- 16082713
TI  - Excretion of resorption products from bioactive glass implanted in rabbit muscle.
AB  - Bioactive glass granules were implanted in the paraspinal muscle of rabbits to
      determine the pathway of the silicon released from bioactive glass in vivo. We
      traced and quantified the silicon released by obtaining 24-h urine and blood
      samples for up to 6 months after implantation. Furthermore, local muscle tissue
      as well as the following organs were resected for chemical and histopathological
      analyses: brain, heart, kidney, liver, lung, lymph nodes, spleen, and thymus. The
      urinary silicon of the group with implanted granules was significantly higher
      than in the sham-operated, control group. The average excretion rate was 2.4
      mg/day, and as such, 100% of the implanted silicon was excreted in 19 weeks. No
      elevated concentrations of silicon were found at the implant sites or in the
      other organs at sacrifice, that is, 24 weeks. The histological appearance of all
      organs was normal throughout. The concentrations of silicon measured in the urine
      were well below saturation and because no significant increase in silicon was
      found in any organ, including kidney, the increased silicon excretion rate was
      within the physiological capacity of rabbits. Therefore, it can be concluded that
      the resorbed silica gel is harmlessly excreted in soluble form through the urine.

PMID- 16082714
TI  - Improvement of detection specificity of Plasmodium-infected murine erythrocytes
      by flow cytometry using autofluorescence and YOYO-1.
AB  - BACKGROUND: Microscopic analysis of blood smears is currently the most frequently
      used method to measure parasitemias in experiments of drug efficacy in murine
      models of malaria. However, it is subjective and labour intensive, which preclude
      its utilization in large-scale evaluation programs. Flow cytometry is an
      alternative method, but due to the limited specificity achieved with the
      currently available techniques, it has not been widely used in murine models of
      malaria during preclinical evaluation. We describe a new flow cytometric method
      based on the differences of autofluorescence and DNA content measured after
      staining with YOYO-1 that are observed in infected erythrocytes compared with
      noninfected erythrocytes. METHODS: Samples of blood from Plasmodium yoelii
      infected animals were fixed with glutaraldehyde, incubated with RNAase, and
      stained with YOYO-1 in 96-well plate format. After acquisition, erythrocytes
      gated in logarithmic side/scatter plots were analyzed in bidimensional FL-2/YOYO
      1 plots in comparison with unidimensional YOYO-1 analysis. RESULTS: The infected
      erythrocytes showed a characteristic pattern of staining different from that of
      noninfected erythrocytes. In routine evaluation, the limit of sensitivity was
      0.01% and the measurements of parasitemia were linear at parasitemias above 0.1%.
      Interestingly, using this approach, infected reticulocytes could be
      differentiated from infected normocytes. CONCLUSIONS: The method described is
      robust, increases the specificity and sensitivity of detection in routine
      testing, and is especially well suited for detection of low parasitemias in
      murine models of malaria.

PMID- 16082715
TI  - Smart 3D-FISH: automation of distance analysis in nuclei of interphase cells by
      image processing.
AB  - BACKGROUND: Detection of fluorescent probes by fluorescence in situ hybridization
      in cells with preserved three-dimensional nuclear structures (3D-FISH) is useful
      for studying the organization of chromatin and localization of genes in
      interphase nuclei. Fast and reliable measurements of the relative positioning of
      fluorescent spots specific to subchromosomal regions and genes would improve
      understanding of cell structure and function. METHODS: 3D-FISH protocol, confocal
      microscopy, and digital image analysis were used. RESULTS: New software (Smart 3D
      FISH) has been developed to automate the process of spot segmentation and
      distance measurements in images from 3D-FISH experiments. It can handle any
      number of fluorescent spots and incorporate images of 4',6-diamino-2-phenylindole
      counterstained nuclei to measure the relative positioning of spot loci in the
      nucleus and inter-spot distance. Results from a pilot experiment using Smart 3D
      FISH on ENL, MLL, and AF4 genes in two lymphoblastic cell lines were satisfactory
      and consistent with data published in the literature. CONCLUSION: Smart 3D-FISH
      should greatly facilitate image processing and analysis of 3D-FISH images by
      providing a useful tool to overcome the laborious task of image segmentation
      based on user-defined parameters and decrease subjectivity in data analysis. It
      is available as a set of plugins for ImageJ software.

PMID- 16082716
TI  - Association studies of transforming growth factor-beta 1 and Alzheimer's disease.
AB  - Substantial laboratory evidence suggests Transforming Growth Factor-beta1 (TGFB1)
      is linked to Alzheimer's Disease (AD) pathology. The purpose of the study was to
      estimate the genetic association of TGFB1 with AD while controlling for
      apolipoprotein E4 allele (APOE4) status, the only well-established genetic risk
      factor for AD. Two study populations were genotyped for the TGFB1-509 and +869
      single nucleotide polymorphisms (SNPs) that have been associated with TGFB1
      levels. Constituting these populations were 203 families from the NIMH AD Genetic
      Initiative with at least two affected siblings and a normal sibling, and a
      population of 126 African-American (AA) AD cases versus 93 age matched controls.
      Results from family-based analyses showed a significant association between the
      TGFB1 -509 SNP and AD for the entire set of 203 families (P = 0.007), and a
      subset of these families without a homozygous APOE4 family member (P = 0.026).
      Results from family-based analyses on the TGFB1 +869 SNP were not significant in
      the 203 families. While associations for the main effects of the TGFB1 +869 and 
      509 SNP with AD in the AA case-control study were also not significant, results
      did indicate that TGFB1 may function as an effect modifier of APOE4 risk.
      Specifically, the odds of AD associated with having at least one APOE4 allele
      increased in an additive fashion with one or two copies of the higher producer
      allele when stratified by TGFB1 -509 genotype and by TGFB1 +869 genotype. Results
      support a role for TGFB1 in AD pathogenesis.

PMID- 16082717
TI  - In vitro and in vivo analysis of macroporous biodegradable poly(D,L-lactide-co
      glycolide) scaffolds containing bioactive glass.
AB  - Recent studies have demonstrated the angiogenic potential of 45S5 Bioglass.
      However, it is not known whether the angiogenic properties of Bioglass remain
      when the bioactive glass particles are incorporated into polymer composites. The
      objectives of the current study were to investigate the angiogenic properties of
      45S5 Bioglass particles incorporated into biodegradable polymer composites. In
      vitro studies demonstrated that fibroblasts cultured on discs consisting of
      specific quantities of Bioglass particles mixed into poly(D,L-lactide-co
      glycolide) secreted significantly increased quantities of vascular endothelial
      growth factor. The optimal quantity of Bioglass particles determined from the in
      vitro experiments was incorporated into three-dimensional macroporous poly(D,L
      lactide-co-glycolide) foam scaffolds. The foam scaffolds were fabricated using
      either compression molding or thermally induced phase separation processes. The
      foams were implanted subcutaneously into mice for periods of up to 6 weeks.
      Histological assessment was used to determine the area of granulation tissue
      around the foams, and the number of blood vessels within the granulation tissue
      was counted. The presence of Bioglass particles in the foams produced a sustained
      increase in the area of granulation tissue surrounding the foams. The number of
      blood vessels surrounding the neat foams was reduced after 2 weeks of
      implantation; however, compression-molded foams containing Bioglass after 4 and 6
      weeks of implantation had significantly more blood vessels surrounding the foams
      compared with foams containing no Bioglass at the same time points. These results
      indicate that composite polymer foam scaffolds containing Bioglass particles
      retain granulation tissue and blood vessels surrounding the implanted foams. The
      use of this polymer composite for tissue engineering scaffolds might provide a
      novel approach for ensuring adequate vascular supply to the implanted device.

PMID- 16082718
TI  - Sorption, degradation and leaching of the fungicide iprodione in a golf green
      under Scandinavian conditions: measurements, modelling and risk assessment.
AB  - In cold climates, fungicides are used on golf greens to prevent snow mould
      causing serious damage to the turf. However, fungicide residues have been
      detected in runoff from golf courses, which may lead to restrictions on use.
      There is therefore an urgent need to improve understanding of the processes
      affecting leaching of fungicides from turfgrass systems to allow identification
      of green construction and management practices that minimize environmental
      impacts. In this study we monitored the leaching of the fungicide iprodione in a
      putting green. Sorption and degradation of iprodione was measured in batch and
      incubation experiments, and the simulation model MACRO was used as a risk
      assessment tool. Degradation of iprodione was bi-phasic, with a rapid initial
      phase (half-life 17 h) caused by enhanced biodegradation. Degradation rates
      slowed considerably after 5 days, with half-lives of up to 38 days. Sorption of
      iprodione was linear, with a K(oc) value of ca 400 cm(3) g(-1). MACRO reasonably
      accurately matched measured drainflows and concentrations of iprodione in soil
      and drainflow. However, peak concentrations in drainage were underestimated,
      which was attributed to preferential finger flow due to water repellency. The
      results also showed the importance of the organic matter content in the green
      root zone in reducing leaching. It was concluded that, with 'reasonable worst
      case' use, losses of iprodione from greens can occur at concentrations exceeding
      water quality limits for aquatic ecosystems. Snow mould problems should be
      tackled by adopting green root zone mixes that minimize leaching and 'best
      management practices' that would avoid the need for intensive prophylactic use of
      fungicides.

PMID- 16082719
TI  - Fate of tritiated didemnin B in mice: excretion and tissue concentrations after
      an intraperitoneal dose.
AB  - Didemnin B has undergone trials in cancer patients, and has antiviral and
      immunosuppressive properties. [(3)H]didemnin B was administered intraperitoneally
      (i.p.) to mice at 320 or 1280 microg/kg. Urine and feces were collected until 168
      h, at which time the mice were killed and tissues collected. Additionally,
      [(3)H]didemnin B was given i.p. at 320 microg/kg, and mice were killed at 1-120 h
      post-dosing. Radiolabel increased rapidly in blood then rapidly declined. Most
      radiolabel in urine, feces and tissues represented parent compound.
      Concentrations of [(3)H]didemnin B were greatest in the liver > gallbladder >
      lower digestive tract congruent with pancreas > spleen > kidney congruent with
      adipose tissue congruent with urinary bladder with urine. The pancreas had the
      longest terminal half-life of the tissues and the highest radioactivity at 7
      days. Intermediate concentrations were in the duodenum congruent with jejunum >
      lung > iliopsoas > stomach congruent with testes congruent with skin > heart. Low
      concentrations were in the humerus congruent with femur congruent with quadriceps
      congruent with triceps >> brain. Fecal excretion accounted for 45.9%-58.3% of the
      dose and declined after 24 h, followed by an increase, suggesting possible
      enterohepatic recycling or an impact of circadian rhythms. Urinary excretion
      accounted for 18.4%-25.2% of the dose, but was minimal after 24 h. The
      concentrations were highest in organs previously found to be sensitive in animals
      and humans. Didemnin B should be evaluated in animal models for treatment of
      pancreatic cancer.

PMID- 16082720
TI  - First-trimester ultrasound diagnosis in a recurrent case of Walker-Warburg
      syndrome.
AB  - We report on two siblings with Walker-Warburg syndrome (WWS) born to a
      consanguineous couple. In the index case, the second-trimester scan showed
      ventricular dilatation and we diagnosed WWS after observing retinal detachment at
      26 weeks' gestation and lissencephaly by 32 weeks' gestation in addition to
      hypoplasia of the cerebellar vermis. The second case was first suspected at 12
      weeks' gestation, when we observed a 2.8-mm nuchal translucency and an unusually
      large hindbrain vesicle. By 14 weeks' gestation, the lateral ventricles were
      clearly enlarged (12-13 mm), at 16 weeks' gestation the vitreous chamber appeared
      to be hyperechogenic, and by 17 weeks' gestation hydrocephalus was evident. The
      couple chose to continue the pregnancy, and during the third trimester
      lissencephaly, major hydrocephalus and polyhydramnios developed. Serial
      ultrasound examination should be offered to a family with a history of WWS and
      therefore a 1 in 4 risk of recurrence. In some cases, recurrence can be suspected
      as early as the first trimester, however the diagnosis cannot be excluded on the
      basis of normal ultrasound appearance until later in pregnancy.

PMID- 16082721
TI  - Ultrasound examination of the endometrium before and after Pipelle endometrial
      sampling.
AB  - OBJECTIVE: To evaluate if, and to what extent, Pipelle de Cornier endometrial
      sampling influences the ultrasonographic features of the endometrium. METHODS:
      This was a prospective descriptive study on 99 consecutive women in whom a
      Pipelle endometrial biopsy was performed. All patients first underwent a
      transvaginal ultrasound evaluation of the uterus. The endometrial thickness (ET)
      was measured and endometrial sonographic features were recorded. Thereafter, a
      Pipelle endometrial biopsy was taken. Finally, the ultrasound examination was
      repeated. The patients' characteristics, the sampling procedure, the endometrial
      histology and the sonographic findings before and after Pipelle biopsy were
      compared. RESULTS: Ninety-nine women, of whom 45% were postmenopausal, entered
      the study. The mean age was 59.0 years (SD, 9.9) for the postmenopausal women,
      and 41.6 years (SD, 8.7) for the rest. On histological examination, endometrial
      cancer was diagnosed in four patients and endometrial hyperplasia in eight
      patients. The average ET before Pipelle sampling was 9.0 mm (SD, 6.6) vs. 8.6 mm
      (SD, 7.0) after biopsy (P < 0.0001). After Pipelle sampling, the endometrium was
      less clearly delineated (P = 0.03) and more echogenic endometrial spots were seen
      (P < 0.0001). If an endometrial three-layer pattern was noted before sampling, it
      was not observed in most women after Pipelle biopsy (P = 0.0003). CONCLUSIONS: ET
      measurements are affected by Pipelle sampling and the quality of the ultrasound
      features tends to be altered by biopsy. Performing the ultrasound examination
      before proceeding with endometrial sampling may therefore improve diagnostic
      accuracy of ultrasound.

PMID- 16082722
TI  - Fetal intracranial hemorrhage (fetal stroke): does grade matter?
AB  - OBJECTIVE: To determine if the severity of antenatally diagnosed hemorrhagic
      fetal brain insults and fetal stroke detected by ultrasound and magnetic
      resonance imaging (MRI) predicts postnatal neurodevelopmental prognosis. METHODS:
      The in-utero presentation and postnatal neurodevelopmental outcome of
      sonographically detected subdural hematoma or fetal stroke presenting as
      intraventricular hemorrhage (IVH) or intraparenchymal brain hemorrhage were
      investigated. RESULTS: Of 33 fetuses diagnosed with hemorrhagic brain lesions, 17
      were electively terminated and two suffered intrauterine fetal demise. Thirteen
      were liveborn, seven by Cesarean delivery and six by spontaneous vaginal
      delivery. One case was lost to follow-up. Eight neonates had moderate to severe
      neurological deficit by a mean age of 35 (range, 6-96) months. One died at 2
      months of age. These nine were diagnosed with Grade III-IV IVH in utero. Four
      neonates had normal neurological outcome by a mean age of 41 (range, 30-48)
      months; these four were diagnosed with subdural hematoma (n = 1) or Grade I-II
      IVH (n = 3) in utero. Fourteen cases were followed up with MRI, which confirmed
      ultrasound findings in 10 (71%) cases. In three (21%) cases MRI diagnosis was
      more accurate and the severity of grading was greater than that obtained on
      ultrasound imaging. Unilateral left hemispheric lesions were much more common
      than right-sided lesions (13 vs. 1, respectively). CONCLUSIONS: An antenatal
      sonographic diagnosis of fetal stroke with IVH Grade III-IV or with brain
      parenchymal involvement appears to be associated with poor neurological outcome.
      MRI may contribute to the accuracy of diagnosis, particularly in Grade II and III
      lesions. Left-sided unilateral lesions are more common than right-sided ones.

PMID- 16082723
TI  - Cavernous lymphangioma of the face and neck: prenatal diagnosis by three
      dimensional ultrasound.
AB  - Cavernous lymphangiomas are characterized by penetration through the subcutaneous
      areas between the muscular septa and represent rare variants of the more common
      superficial lymphangioma. Although frequently described in the fetus when
      involving the posterior aspect of the neck (i.e. cystic hygroma), involvement of
      the craniofacial region is rare. We describe the prenatal findings in a case of
      cavernous lymphangioma of the fetal face and neck, which extended caudally to
      envelop the larynx and the trachea. The anomaly was assessed by two- and three
      dimensional (3D) ultrasound. The latter approach was used thoroughly both during
      counseling with the couple and during consultation with the pediatric surgeon.
      This case report confirms the usefulness of the 3D approach in the management of
      rare fetal anomalies. In particular, the possibility of navigating the volume
      facilitated consultation with the pediatric surgeon and counseling of the
      parents.

PMID- 16082724
TI  - Fetal trunk and head volume measured by three-dimensional ultrasound at 11 + 0 to
      13 + 6 weeks of gestation in chromosomally normal pregnancies.
AB  - OBJECTIVE: To establish the relationship between fetal trunk and head volume
      measured by three-dimensional (3D) ultrasound and gestational age at 11 + 0 to 13
      + 6 weeks of gestation. METHODS: The fetal trunk and head volume were measured
      using 3D ultrasound in 417 chromosomally normal fetuses from singleton
      pregnancies at 11 + 0 to 13 + 6 (median, 12 + 0) weeks of gestation. Regression
      analysis was used to determine the significance of the association between fetal
      volume and gestational age. The Bland-Altman analysis was used to compare the
      measurement agreement and bias for a single examiner and between different
      examiners. RESULTS: The fetal trunk and head volume increased linearly with
      gestation from a mean of 5.8 mL at 11 + 0 weeks to 33.3 mL at 13 + 6 weeks and 1
      SD was 4.4 mL. There was also a significant linear association between fetal
      volume and crown-rump length (CRL), from a mean of 5.1 mL at a CRL of 45 mm to
      37.5 mL at a CRL of 84 mm and 1 SD was 2.7 mL. However, within this gestational
      range, a doubling in CRL, from a mean of 48 mm at 11 + 0 weeks to 79 mm at 13 + 6
      weeks, was associated with a 5-6-fold increase in fetal volume. The mean
      difference in fetal volume between paired measurements by the same sonographer
      was -0.87 mL (95% limits of agreement, -2.31 to 4.05 mL) and the mean difference
      between paired measurements by two sonographers was -1.09 mL (-5.49 to 3.32 mL).
      CONCLUSIONS: 3D ultrasound can provide a reproducible measurement of the fetal
      trunk and head volume in early pregnancy. At between 11 + 0 and 13 + 6 weeks
      there is a 5-6-fold increase in fetal volume but only a doubling in CRL.

PMID- 16082725
TI  - Pathogenesis of urethral funneling in women with stress urinary incontinence
      assessed by introital ultrasound.
AB  - OBJECTIVE: The incidence of urethral funneling (UF) seen in women with stress
      urinary incontinence (SUI) during straining is reported to range from 18.6% to
      97.4%. Its morphologic basis is unknown. The aim of the present study was to
      determine whether SUI patients with and without UF differ in terms of history,
      urodynamic results and magnetic resonance imaging (MRI) findings. PATIENTS AND
      METHODS: Fifty-four women (mean age 52 +/- 11 years) with a history of SUI
      confirmed by clinical and urodynamic findings were included in the study. UF was
      demonstrated by introital ultrasound performed at a bladder filling volume of 300
      mL during maximal straining. MRI for assessment of the urethra, levator ani
      muscle and endopelvic fascia was performed using axial proton-density-weighted
      sequences. RESULTS: UF was demonstrated by introital ultrasound in 59% of the
      patients with SUI (Group 1) and was absent in 41% (Group 2). There were no
      differences between the two groups in mean age (P = 0.208), the incidence of mild
      prolapse of the anterior vaginal wall (Aa, Ba; stage I; P = 0.741), and
      urodynamic parameters (urethral closure pressure at rest; P = 0.507). The
      percentages of nulliparous and parous women were 22% and 78% in Group 1 and 54%
      and 46% in Group 2 (P = 0.013). The two groups did not differ in the MRI
      demonstration of morphologic defects of the urethra, levator ani muscle and
      endopelvic fascia or of combined defects. CONCLUSIONS: The results of the present
      study did not elucidate the pathogenesis of UF. The demonstration of UF crucially
      depends on the examination technique employed.

PMID- 16082726
TI  - The influence of natural antibody specificity on antigen immunogenicity.
AB  - The natural antibody repertoire in humans, apes and Old World primates is
      distinct from the repertoire of all other placental mammals, and encodes
      antibodies specific for the carbohydrate epitope Galalpha1-3Galbeta1-4GlcNAc-R
      (alphaGal). Here, we examined whether conjugating antigens to the alphaGal
      epitope can augment their immunogenicity in alpha(1,3)galactosyltransferase
      knockout mice (GT0 mice) which, like humans, produce alphaGal-specific
      antibodies. Immunization of GT0 mice with BSA conjugated to alphaGal (alphaGal
      BSA) led to significant production of anti-BSA IgG antibodies without the need
      for adjuvant. This response was dependent on the presence of alphaGal-reactive
      antibodies. Immunization of wild-type mice with alphaGal-BSA failed to induce an
      anti-BSA response. The presence of alphaGal-reactive antibodies also led to an
      increase in the T cell response to BSA following immunization with alphaGal-BSA
      when compared with mice that received BSA alone, resulting in an increased
      frequency of IFN-gamma- and IL-4-producing BSA-specific T cells. In addition, the
      ability to produce alphaGal-reactive antibodies enhanced the cytotoxic T
      lymphocyte anti-viral antigen response following vaccination with murine leukemia
      virus transformed cell lines that express alphaGal on their cell surface. Natural
      antibodies that bind alphaGal therefore play a key role in increasing the
      efficiency of priming to antigens decorated with alphaGal epitopes.

PMID- 16082727
TI  - Early regulation of CD8 T cell alloreactivity by CD4+CD25- T cells in recipients
      of anti-CD154 antibody and allogeneic BMT is followed by rapid peripheral
      deletion of donor-reactive CD8+ T cells, precluding a role for sustained
      regulation.
AB  - While acquisition of regulatory function by CD4+CD25- T cells has been reported
      following antigenic stimulation, "naturally occurring" regulatory CD4+ T cells
      (Treg) are believed to express CD25. We examined the mechanisms involved in
      peripheral CD8 T cell tolerance by induction of mixed chimerism using non
      myeloablative conditioning with low-dose (3 Gy) total body irradiation and anti
      CD154 antibody. Recipient CD4+ T cells were initially required for the induction
      of CD8 cell tolerance, but were not needed beyond 2 weeks. Depletion of CD25+
      Treg prior to bone marrow transplantation and blockade of IL-2 with neutralizing
      antibody did not impede tolerance induction. Tolerance was dependent on CTLA4,
      but not on IFN-gamma. In C57BL/6 mice containing a fraction of 2C TCR transgenic
      CD8+ T cells, which recognize the MHC class I alloantigen Ld, induction of
      chimerism with L(d+), but not Ld-, bone marrow cells led to deletion of
      peripheral 2C+ CD8+ cells within 1 week in peripheral blood and spleen. Complete
      deletion required the presence of recipient CD4+ T cells. Thus, a novel, rapid
      form of regulation by CD4+CD25- T cells permits initial CD8 T cell tolerance in
      this model. Rapid peripheral deletion of donor-specific CD8 T cells precludes an
      ongoing requirement for CD4 T cell-mediated regulation.

PMID- 16082728
TI  - Carbohydrates located on the top of the "cap" contribute to the adhesive and
      enzymatic functions of vascular adhesion protein-1.
AB  - Vascular adhesion protein 1 (VAP-1) is an endothelial adhesion molecule with an
      enzymatic activity. It deaminates biogenic amines, resulting in the formation of
      aldehydes and hydrogen peroxide. During the enzymatic reaction a transient Schiff
      base is formed between endothelial VAP-1 and its leukocytic ligand, and this
      interaction is important for lymphocyte adhesion. VAP-1 monomer has six potential
      N-linked, and three putative O-linked glycosylation sites and an SSSS sequence
      potentially forming an attachment site for an adjacent O-linked site. In this
      work we modeled the carbohydrate decorations on a structural model of VAP-1, and
      studied which of those potential glycosylation sites are utilized, and whether
      those decorations accessible to a lymphocyte ligand are important in lymphocyte
      adhesion and enzymatic activity of VAP-1. We show that, unlike the O-linked
      attachment sites, all six N-linked glycosylation sites are in use. Furthermore,
      mutation of the N-linked attachment sites strategically located on the top of the
      molecule reduces lymphocyte adhesion in non-static conditions, and enhances the
      catalytic activity of membrane-bound human VAP-1 in static conditions, suggesting
      that glycosylation regulates the functional properties of VAP-1.

PMID- 16082729
TI  - Abstracts of the 28th Annual Meeting of the Japan Neuroscience Society. July 26
      28, 2005, Yokohama, Japan.

PMID- 16082730
TI  - Carotenoids and dietary lipids in health and disease. Proceedings of a
      conference. December 9-12, 2004. Krakow, Poland.

PMID- 16082731
TI  - British Geriatrics Society. Abstracts to the autumn meeting, 6-8 October 2004,
      Harrogate, United Kingdom.

PMID- 16082732
TI  - Abstracts of the GEC-ESTRO Meeting (Groupe Europeen de Curietherapie, European
      Society for Therapeutic Radiology and Oncology). 6-7 May 2005, Budapest, Hungary.

PMID- 16082733
TI  - Abstracts of the European Drug Utilisation Research Group Conference, Coleraine,
      N. Ireland, 29 June-2 July 2005.

PMID- 16082734
TI  - Abstracts of the 2nd Joint Meeting of the European Calcified Tissue Society and
      the International Bone and Mineral Society. 25-29 June 2005, Geneva, Switzerland.

PMID- 16082735
TI  - Peginterferon alfa-2b and ribavirin for treatment-refractory chronic hepatitis C.
AB  - BACKGROUND/AIMS: Treatment regimens with pegylated interferons have yielded
      improved response rates, compared with conventional interferon-based regimens,
      for chronic hepatitis C. However, little is known about the utility of such
      regimens for individuals who failed to respond to prior conventional interferon
      based treatment. METHODS: 182 patients who had previously failed to eliminate
      circulating hepatitis C virus 24 weeks after completion of a multi-week course of
      either interferon monotherapy or interferon in combination with ribavirin were
      treated with peginterferon alfa-2b weekly and ribavirin daily for 48 weeks.
      RESULTS: The sustained viral response, was 20% (23/116) in previous non
      responders and 55% (36/66) in previous relapsers (P<0.001). In previous non
      responders, the sustained viral response in those with viral genotype 1 was 17%
      (19/109) compared to 57% (4/7) in those with genotypes 2 and 3 (P=0.03). In
      previous relapsers, the sustained viral response in those with viral genotype 1
      was 53% (26/49) compared to 59% (10/17) with genotypes 2 and 3 (P=0.78).
      CONCLUSIONS: The response to pegylated interferon and ribavirin in previous non
      responders with genotypes 2 and 3 and in prior relapsers with chronic hepatitis C
      is comparable to overall sustained viral response rates seen in previously
      untreated patients.

PMID- 16082736
TI  - International, multicenter, randomized, controlled study comparing dynamically
      individualized versus standard treatment in patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: The aim of this study was to increase virologic response rates
      by individualized treatment according to the early virologic response. METHODS:
      Serum HCV-RNA was frequently quantified in patients with chronic hepatitis C
      (n=270) treated with peginterferon alfa-2a (180 microg/week) and ribavirin (1000
      1200 mg/day). After 6 weeks patients were classified as rapid (RVR), slow (SPR),
      flat (FPR), or null responders (NUR) and randomized within each viral kinetic
      class to continue therapy either with an individualized or standard regimen.
      Individualized therapy comprised peginterferon monotherapy (48 weeks) or shorter
      combination therapy (24 weeks) for RVR, triple therapy with histamine (1 mg/day)
      (48 weeks) or prolonged combination therapy (72 weeks) for SPR, triple therapy
      for FPR, and high-dose peginterferon (360 microg/week) plus ribavirin for NUR
      patients. RESULTS: Patients were categorized as RVR (n=171), SPR (n=65), FPR
      (n=10), or NUR (n=22). Overall end-of-treatment and sustained virologic response
      rates were 77 and 60% in the individualized and 77 and 66% in the standard
      treatment arm, respectively. Histamine in addition to peginterferon and ribavirin
      and high-dose peginterferon plus ribavirin did not improve virologic response
      rates in patients with FPR and NUR, respectively. CONCLUSIONS: An improvement in
      virologic efficacy was not achieved with the available individualized treatment
      options.

PMID- 16082737
TI  - Proceedings of the 12th International Congress of Immunology and the 4th Annual
      Conference of the Federation of Clinical Immunology Societies. July 18-23, 2004.
      Montreal, Canada.

PMID- 16082738
TI  - The case for anti-reflux surgery.

PMID- 16082739
TI  - Surgical tracheostomy--how I do it.

PMID- 16082740
TI  - A model for training in grommet insertion.

PMID- 16082741
TI  - Intra-operative femoral nerve stimulation as an aid in tibial tuberosity
      transfer.

PMID- 16082742
TI  - A user-friendly technique for distal locking of intramedullary nails.

PMID- 16082743
TI  - The multi-functional surgical device.

PMID- 16082744
TI  - Abstracts from the 8th Leipzig Workshop "Predictive Medicine" and the 1st
      International Workshop "Slide Based Cytometry". May 15-17, 2003, Leipzig,
      Germany.

PMID- 16082745
TI  - Innovative suction apparatus: two low-cost techniques for non-industrialised
      countries.

PMID- 16082746
TI  - An alternative use of pressure infusor in thyroid surgery.

PMID- 16082747
TI  - A simple technique to maintain fracture reduction and facilitate application of
      long-arm plaster in fractures of forearm bones.

PMID- 16082748
TI  - Impact of junior doctor education on drug allergy documentation.

PMID- 16082749
TI  - Implementing a 'New Deal' compliant SHO rota.

PMID- 16082750
TI  - Timetable design.

PMID- 16082751
TI  - A significant bias in the results?

PMID- 16082752
TI  - High risk of lower limb neuropraxia and litigations for a better view of the
      perineum.

PMID- 16082753
TI  - Reconstruction after skin sparing mastectomy.

PMID- 16082755
TI  - Abstracts of the Annual Main Meeting of the Society for Experimental Biology, 11
      15 July 2005, Barcelona, Spain.

PMID- 16082756
TI  - Abstracts from the 2004 Scientific Sessions of the American Heart Association.
      November 7-10, 2004, New Orleans, Louisiana, USA.

PMID- 16082757
TI  - Oxygen administration can reverse neurological deficit following carotid cross
      clamping.

PMID- 16082758
TI  - The William Nelson ECG Quiz.

PMID- 16082759
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 16082760
TI  - 'PTSD in nurses': the March viewpoint strikes a chord.

PMID- 16082761
TI  - 'PTSD in nurses': the March viewpoint strikes a chord.

PMID- 16082762
TI  - 'PTSD in nurses': the March viewpoint strikes a chord.

PMID- 16082763
TI  - 'PTSD in nurses': the March viewpoint strikes a chord.

PMID- 16082764
TI  - 'PTSD in nurses': the March viewpoint strikes a chord.

PMID- 16082765
TI  - 'PTSD in nurses': the March viewpoint strikes a chord.

PMID- 16082766
TI  - 'PTSD in nurses': the March viewpoint strikes a chord.

PMID- 16082767
TI  - 'PTSD in nurses': the March viewpoint strikes a chord.

PMID- 16082768
TI  - 'PTSD in nurses': the March viewpoint strikes a chord.

PMID- 16082769
TI  - Maternal origin of extra marker chromosome 1Q31.1-qter and 13pter-q12.12 in a
      child with dysmorhic features.
AB  - Maternal origin of extra marker chromosome Iq31.l-qter and 13pter-q12.12 in a
      child with dysmorphic features: We describe a twenty-days-old female child with
      dysmorphic features and chromosomal analysis with GTG-banding revealed an extra
      marker chromosome. Fluorescence in situ hybridization (FISH) study of extra
      marker chromosome confirmed to be maternal der(13) chromosome, contained 1q31.1
      qter and 13pter-q11 chromosomal material and resulted from a maternal balanced
      translocation t(1;13)(q31.1; q12.12). The child had the majority of trisomy 1q
      clinical features: dysmorphic features, micropthalmia, high arched palate, long
      philthrum, micrognathia, hypertelorism, low set ears, short sternum, overlapping
      fingers, valgus of wrists, right knee and ankle joints were in flexion
      contractures. This is the first case of trisomy 1q with an extra marker
      chromosome which also contained chromosome 13pter-q12.12 material.

PMID- 16082770
TI  - The microorganism community in an aerobic denitrification membrane bioreactor by
      16S rDNA based molecular biotechnology.
AB  - In this study, the performance and microbial community in a submerged membrane
      bioreactor were investigated for different hydraulic retention times. The removal
      efficiencies of chemical oxygen demand, total phosphorus, suspended solid and
      heterotrophic bacteria did not differ significantly with different hydraulic
      retention times but the total nitrogen removal efficiency increased when the
      hydraulic retention time increased. Aerobic denitrification occurred during the
      membrane bioreactor process at hydraulic retention time of 20 hours and
      Thiosphera pantotropha was identified as the aerobic denitrifier by the clone
      denaturing gradient gel electrophoresis method. Another denitrifying Fe+2
      oxidizing bacteria was also identified at hydraulic retention time of 20 hours.
      In contrast, no denitrifying bacteria were identified at hydraulic retention time
      of 5 hours.

PMID- 16082772
TI  - Medicare program; prospective payment system and consolidated billing for skilled
      nursing facilities for FY 2006. Final rule.
AB  - In this final rule we update the payment rates used under the prospective payment
      system (PPS) for skilled nursing facilities (SNFs), for fiscal year (FY) 2006.
      Annual updates to the PPS rates are required by section 1888(e) of the Social
      Security Act (the Act), as amended by the Medicare, Medicaid, and SCHIP Balanced
      Budget Refinement Act of 1999 (BBRA), the Medicare, Medicaid, and SCHIP Benefits
      Improvement and Protection Act of 2000 (BIPA), and the Medicare Prescription
      Drug, Improvement, and Modernization Act of 2003 (MMA), relating to Medicare
      payments and consolidated billing for SNFs. This final rule also responds to
      public comments submitted on the proposed rule published on May 19, 2005 (70 FR
      29070), and promulgates provisions set forth in that proposed rule, along with
      several additional technical revisions to the regulations.

PMID- 16082771
TI  - Inhibition of mammary tumor growth by a novel nontoxic retinoid: chemotherapeutic
      evaluation of a C-linked analog of 4-HPR-glucuronide.
AB  - Previous studies from our laboratory suggest that 4-HPROG, the O-glucuronide
      derivative of 4-HPR, has improved mammary cancer chemopreventive/ antitumor
      activities as well as reduced toxicity, as compared to 4-HPR. This O-linked
      glucuronide derivative is a substrate to the P-glucuronidase enzyme and may also
      undergo hydrolysis in vivo to the vitamin A metabolite, retinoic acid, that is
      toxic at high concentrations. In an effort to improve analog potency relative to
      its toxicity, the 4-HPROG's phenolic oxygen was replaced with a methylene group,
      thus preventing biological cleavage of the glucuronide moiety. The resulting C
      linked analog, 4-HPR-C-glucuronide (4-HPRCG), cannot be hydrolyzed to 4-HPR. The
      results of this study show that 4-HPRCG is an effective chemotherapeutic agent
      that caused 49% regression of DMBA-induced mammary tumors in rats, while showing
      almost no side-effects that are often observed with other natural or synthetic
      retinoids, such as a reduction in blood retinol level, elevation in blood
      triglyceride (TG) level, and decrease in bone mineral content (BMC). These
      results suggest that 4-HPRCG should be considered as a better candidate for
      breast cancer treatment.

PMID- 16082773
TI  - Medicare program; hospice wage index for fiscal year 2006. Final rule.
AB  - This final rule sets forth the hospice wage index for fiscal year 2006 and
      identifies the revised labor market and metropolitan core based statistical
      areas. In addition, this final rule responds to public comments and implements
      provisions of sections 408 and 946 of the Medicare Prescription Drug,
      Improvement, and Modernization Act of 2003.

PMID- 16082774
TI  - An HIV-infected man with odynophagia and rash.

PMID- 16082775
TI  - Inappropriate antibiotic use.

PMID- 16082776
TI  - Diagnosing pulmonary embolism in a rural setting.

PMID- 16082777
TI  - Nurse practitioners.

PMID- 16082779
TI  - Distribution of two selenonucleosides among the selenium-containing tRNAs from
      Methanococcus vannielii.
AB  - Naturally occurring seleno-tRNAs from Methanococcus vannielii account for 13-20%
      of the total tRNA population. Two different selenium-modified nucleosides were
      detected in these seleno-tRNAs. Of the total selenium incorporated, about 60% is
      present in 5-methylaminomethyl-2-selenouridine, and the other 40% occurs in a
      second selenonucleoside with spectral characteristics typical of a derivative of
      2-selenouridine. The 5-methylaminomethyl-2-selenouridine was found in the seleno
      tRNA species present in the early fractions of a linear salt gradient elution
      profile from a reversed-phase chromatographic system 5 (RPC-5) column, whereas
      the second selenonucleoside occurred in the tRNA species eluted late in the
      profile.

PMID- 16082778
TI  - Evolutionary clues to eukaryotic DNA clamp-loading mechanisms: analysis of the
      functional constraints imposed on replication factor C AAA+ ATPases.
AB  - Ring-shaped sliding clamps encircle DNA and bind to DNA polymerase, thereby
      preventing it from falling off during DNA replication. In eukaryotes, sliding
      clamps are loaded onto DNA by the replication factor C (RFC) complex, which
      consists of five distinct subunits (A-E), each of which contains an AAA+ module
      composed of a RecA-like alpha/beta ATPase domain followed by a helical domain.
      AAA+ ATPases mediate chaperone-like protein remodeling. Despite remarkable
      progress in our understanding of clamp loaders, it is still unclear how
      recognition of primed DNA by RFC triggers ATP hydrolysis and how hydrolysis leads
      to conformational changes that can load the clamp onto DNA. While these questions
      can, of course, only be resolved experimentally, the design of such experiments
      is itself non-trivial and requires that one first formulate the right hypotheses
      based on preliminary observations. The functional constraints imposed on protein
      sequences during evolution are potential sources of information in this regard,
      inasmuch as these presumably are due to and thus reflect underlying mechanisms.
      Here, rigorous statistical procedures are used to measure and compare the
      constraints imposed on various RFC clamp-loader subunits, each of which performs
      a related but somewhat different, specialized function. Visualization of these
      constraints, within the context of the RFC structure, provides clues regarding
      clamp-loader mechanisms--suggesting, for example, that RFC-A possesses a
      triggering component for DNA-dependent ATP hydrolysis. It also suggests that,
      starting with RFC-A, four RFC subunits (A-D) are sequentially activated through a
      propagated switching mechanism in which a conserved arginine swings away from a
      position that disrupts the catalytic Walker B region and into contact with DNA
      thread through the center of the RFC/clamp complex. Strong constraints near
      regions of interaction between subunits and with the clamp likewise provide clues
      regarding possible coupling of hydrolysis-driven conformational changes to the
      clamp's release and loading onto DNA.

PMID- 16082780
TI  - On the paper by E. F. Sato and coauthors "Oxidative stress promotes the
      regression of fetal liver hemopoiesis".

PMID- 16082781
TI  - [International standards for medical laboratories].

PMID- 16082782
TI  - [Current research on angong niuhuang pills].

PMID- 16082783
TI  - Modeling supply and return line dynamics for an electrohydraulic actuation
      system.
AB  - This paper presents a model of an electrohydraulic fatigue testing system that
      emphasizes components upstream of the servovalve and actuator. Experiments showed
      that there are significant supply and return pressure fluctuations at the
      respective ports of the servovalve. The model presented allows prediction of
      these fluctuations in the time domain in a modular manner. An assessment of
      design changes was done to improve test system bandwidth by eliminating the
      pressure dynamics due to the flexibility and inertia in hydraulic hoses. The
      model offers a simpler alternative to direct numerical solutions of the governing
      equations and is particularly suited for control-oriented transmission line
      modeling in the time domain.

PMID- 16082784
TI  - On simplified predictive control as a generalization of least-squares dynamic
      matrix control.
AB  - Simplified predictive control (SPC) of a single-input single-output control
      scheme is compared to the more sophisticated, least-squares formulation of
      dynamic matrix control (DMC) and its move-suppressed variant (move-suppressed
      DMC) for a typical two time-step control horizon. A closed-loop, continuous
      analysis shows that the discrete form of SPC generalizes the discrete DMC
      algorithm, and its variants, to control responses faster than one-half the
      process response time while remaining well conditioned.

PMID- 16082785
TI  - Internal model control structure using adaptive inverse control strategy.
AB  - In this paper, we propose a new adaptive internal model control scheme based on
      adaptive finite impulse response filters. This scheme provides the same design
      procedure for both minimum and nonminimum phase plants. The plants under
      consideration may contain time delay. The tracking objective is accomplished for
      both invertible and noninvertible stable plants. The internal model of the plant
      and its inverse are estimated by recursive least-squares and least-mean-squares
      algorithms, respectively. The closed loop is designed such that the system from
      the reference input to the plant output can be approximately represented by a
      pure delay. The effect of the process zeros on the output is compensated by using
      adaptive finite impulse response filters. This avoids the cancellation of
      noncancellable zeros of the plant and forces the plant output to track the
      reference input with a delay. The stability of the closed loop for both minimum
      and nonminimum phase systems is guaranteed. Computer simulation and laboratory
      scale experimental results are included in the paper to demonstrate the
      effectiveness of the proposed method.

PMID- 16082786
TI  - PID controller tuning for the first-order-plus-dead-time process model via
      Hermite-Biehler theorem.
AB  - This paper discusses PID stabilization of a first-order-plus-dead-time (FOPDT)
      process model using the stability framework of the Hermite-Biehler theorem. The
      FOPDT model approximates many processes in the chemical and petroleum industries.
      Using a PID controller and first-order Pade approximation for the transport
      delay, the Hermite-Biehler theorem allows one to analytically study the stability
      of the closed-loop system. We derive necessary and sufficient conditions for
      stability and develop an algorithm for selection of stabilizing feedback gains.
      The results are given in terms of stability bounds that are functions of plant
      parameters. Sensitivity and disturbance rejection characteristics of the proposed
      PID controller are studied. The results are compared with established tuning
      methods such as Ziegler-Nichols, Cohen-Coon, and internal model control.

PMID- 16082787
TI  - An improved PCA method with application to boiler leak detection.
AB  - Principal component analysis (PCA) is a popular fault detection technique. It has
      been widely used in process industries, especially in the chemical industry. In
      industrial applications, achieving a sensitive system capable of detecting
      incipient faults, which maintains the false alarm rate to a minimum, is a crucial
      issue. Although a lot of research has been focused on these issues for PCA-based
      fault detection and diagnosis methods, sensitivity of the fault detection scheme
      versus false alarm rate continues to be an important issue. In this paper, an
      improved PCA method is proposed to address this problem. In this method, a new
      data preprocessing scheme and a new fault detection scheme designed for
      Hotelling's T2 as well as the squared prediction error are developed. A dynamic
      PCA model is also developed for boiler leak detection. This new method is applied
      to boiler water/steam leak detection with real data from Syncrude Canada's
      utility plant in Fort McMurray, Canada. Our results demonstrate that the proposed
      method can effectively reduce false alarm rate, provide effective and correct
      leak alarms, and give early warning to operators.

PMID- 16082788
TI  - Cascade generalized predictive control strategy for boiler drum level.
AB  - This paper proposes a cascade model predictive control scheme for boiler drum
      level control. By employing generalized predictive control structures for both
      inner and outer loops, measured and unmeasured disturbances can be effectively
      rejected, and drum level at constant load is maintained. In addition, nonminimum
      phase characteristic and system constraints in both loops can be handled
      effectively by generalized predictive control algorithms. Simulation results are
      provided to show that cascade generalized predictive control results in better
      performance than that of well tuned cascade proportional integral differential
      controllers. The algorithm has also been implemented to control a 75-MW boiler
      plant, and the results show an improvement over conventional control schemes.

PMID- 16082789
TI  - Automated estimator parameter selection for an IBM head/disk assembly.
AB  - This paper presents the application of a discrete adaptive observer (DAO) to an
      IBM head/disk assembly system. Because of the difficulties in tuning, a genetic
      algorithm is implemented off-line to obtain optimal observer parameters for the
      DAO. Simulations show that the genetic algorithm is successful in choosing
      appropriate observer gains. Furthermore, as a result of these optimal gains, the
      observer state and parameter estimates converge accurately and quickly.

PMID- 16082790
TI  - Globally linearized control on diabatic continuous stirred tank reactor: a case
      study.
AB  - This paper focuses on the promise of globally linearized control (GLC) structure
      in the realm of strongly nonlinear reactor system control. The proposed nonlinear
      control strategy is comprised of: (i) an input-output linearizing state feedback
      law (transformer), (ii) a state observer, and (iii) an external linear
      controller. The synthesis of discrete-time GLC controller for single-input single
      output diabatic continuous stirred tank reactor (DCSTR) has been studied first,
      followed by the synthesis of feedforward/feedback controller for the same reactor
      having dead time in process as well as in disturbance. Subsequently, the
      multivariable GLC structure has been designed and then applied on multi-input
      multi-output DCSTR system. The simulation study shows high quality performance of
      the derived nonlinear controllers. The better-performed GLC in conjunction with
      reduced-order observer has been compared with the conventional proportional
      integral controller on the example reactor and superior performance has been
      achieved by the proposed GLC control scheme.

PMID- 16082791
TI  - Guest editors' introduction: workforce competencies in behavioral health.

PMID- 16082792
TI  - Achieving the promise through workforce transformation: a view from the Center
      for Mental Health Services.

PMID- 16082793
TI  - Patient perspectives on provider competence: a view from the Depression and
      Bipolar Support Alliance.

PMID- 16082794
TI  - "You are here": putting psychiatric residency training in context.

PMID- 16082795
TI  - The fundamentals of workforce competency: implications for behavioral health.
AB  - Increasing attention is being directed to the competency of those who deliver
      healthcare in the United States. In behavioral health, there is growing
      recognition of the need to define, teach, and assess essential competencies.
      Since attention to this issue in behavioral health is relatively recent, there is
      much to be gained by learning from the principles, definitions, and conceptual
      models of competency that have been developed in other fields. This article
      outlines the forces that drive the current focus on competency of the healthcare
      workforce. Relevant history, principles, definitions, and models that have
      evolved through research and application in business and industry are reviewed.
      From this analysis, recommendations are offered to guide future work on
      competencies in behavioral health.

PMID- 16082796
TI  - Strategies for developing competency models.
AB  - There is an emerging trend within healthcare to introduce competency-based
      approaches in the training, assessment, and development of the workforce. The
      trend is evident in various disciplines and specialty areas within the field of
      behavioral health. This article is designed to inform those efforts by presenting
      a step-by-step process for developing a competency model. An introductory
      overview of competencies, competency models, and the legal implications of
      competency development is followed by a description of the seven steps involved
      in creating a competency model for a specific function, role, or position. This
      modeling process is drawn from advanced work on competencies in business and
      industry.

PMID- 16082797
TI  - Best practices for assessing competence and performance of the behavioral health
      workforce.
AB  - The need for mechanisms to assess the competence and performance of the
      behavioral health workforce has received increasing attention. This article
      reviews strategies used in general medicine and other disciplines for assessing
      trainees and practitioners. The possibilities and limitations of various
      approaches are reviewed, and the implications for behavioral health are
      addressed. A conceptual model of competence is presented, and practical
      applications of this model are reviewed. Finally, guidelines are proposed for
      building competency assessment protocols for behavioral health.

PMID- 16082798
TI  - Workforce competencies in behavioral health: an overview.
AB  - Competency-based training approaches are being used more in healthcare to guide
      curriculum content and ensure accountability and outcomes in the educational
      process. This article provides an overview of the state of competency development
      in the field of behavioral health. Specifically, it identifies the groups and
      organizations that have conducted and supported this work, summarizes their
      progress in defining and assessing competencies, and discusses both the obstacles
      and future directions for such initiatives. A major purpose of this article is to
      provide a compendium of current competency efforts so that these might inform and
      enhance ongoing competency development in the varied behavioral health
      disciplines and specialties. These varied resources may also be useful in
      identifying the core competencies that are common to the multiple disciplines and
      specialties.

PMID- 16082799
TI  - Curriculum resources for training direct care providers in public sector mental
      health.
AB  - Direct care personnel who do not have graduate-level professional degrees provide
      a substantial amount of client care in mental health organizations across the
      nation. Training for them is minimal in many settings. This shortcoming may
      negatively affect client care, staff recruitment and retention, and the effective
      use of scarce resources. In this paper, we identify and review curriculum
      resources available to mental health organizations interested in implementing or
      enhancing training programs for direct care personnel. These include two relevant
      competency sets and six portable training curricula, as well as information on
      how to access these resources.

PMID- 16082800
TI  - Report of recommendations: the Annapolis Coalition Conference on Behavioral
      Health Work Force Competencies.
AB  - In May 2004, the Annapolis Coalition on Behavioral Health Workforce Education
      convened a national meeting on the identification and assessment of competencies.
      The Conference on Behavioral Health Workforce Competencies brought leading
      consumer and family advocates together with other experts on competencies from
      diverse disciplines and specialties in the fields of both mental health care and
      substance use disorders treatment. Aided by experts on competency development in
      business and medicine, conference participants have generated 10 consensus
      recommendations to guide the future development of workforce competencies in
      behavioral health. This article outlines those recommendations. A collaborative
      effort to identify a set of core or common competencies is envisioned as a key
      strategy for advancing behavioral health education, training, and other workforce
      development initiatives.

PMID- 16082801
TI  - A hierarchical model for estimating response time distributions.
AB  - We present a statistical model for inference with response time (RT)
      distributions. The model has the following features. First, it provides a means
      of estimating the shape, scale, and location (shift) of RT distributions. Second,
      it is hierarchical and models between-subjects and within-subjects variability
      simultaneously. Third, inference with the model is Bayesian and provides a
      principled and efficient means of pooling information across disparate data from
      different individuals. Because the model efficiently pools information across
      individuals, it is particularly well suited for those common cases in which the
      researcher collects a limited number of observations from several participants.
      Monte Carlo simulations reveal that the hierarchical Bayesian model provides more
      accurate estimates than several popular competitors do. We illustrate the model
      by providing an analysis of the symbolic distance effect in which participants
      can more quickly ascertain the relationship between nonadjacent digits than that
      between adjacent digits.

PMID- 16082802
TI  - The visual search analogue of latent inhibition: implications for theories of
      irrelevant stimulus processing in normal and schizophrenic groups.
AB  - Latent inhibition (LI) is a robust phenomenon that is demonstrated when a
      previously inconsequential stimulus is less effective in a new learning situation
      than a novel stimulus. Despite LI's simplicity, there is considerable
      disagreement as to its theoretical basis. Attentional theories claim that
      unattended stimulus preexposures reduce stimulus associability. Alternatively, it
      has been asserted that associability is unaffected and that LI is a result of
      competition/retrieval processes. The present article reviews a series of visual
      search studies, some with normal subjects, both undifferentiated and divided into
      low and high schizotypals, and others with pathologies that entail dysfunctional
      attention, such as schizophrenia, Parkinson's disease, and anxiety. The visual
      search conditions were designed to model those of traditional LI experiments,
      while tapping attentional processes independently of the learning scores that
      index LI. A variety of evidence from these and other studies is used to support
      the involvement of attentional and retrieval processes in LI. A model of the
      mechanism of action of these processes in LI is presented, together with its
      application to schizophrenia.

PMID- 16082804
TI  - Compatibility effects based on stimulus and response numerosity.
AB  - Four choice reaction time experiments documented a stimulus-response (S-R)
      compatibility effect involving the numbers of stimuli and responses. In
      Experiment 1, the stimulus consisted of one or two tones, and the correct
      response was either one or two taps of a response key. Responses were much faster
      with a compatible S-R assignment, in which the number of taps matched the number
      of tones, than with an incompatible assignment in which these numbers mismatched.
      Experiments 2 and 3 replicated this effect, using visual stimuli and bimodal
      stimuli, respectively, suggesting that auditory/manual rhythmic compatibility is
      not essential to it. Experiment 4 showed that an analogous but smaller effect is
      obtained when stimuli are the digits 1 and 2. This new numerosity-based
      compatibility effect has general theoretical implications regarding the
      mechanisms responsible for compatibility effects and practical implications for
      interface design.

PMID- 16082805
TI  - Stimulus-response compatible orienting and the effect of an action not taken:
      perception delayed is automaticity denied.
AB  - Orienting to a signal source is widely viewed as automatic in the sense that it
      is triggered by the stimulus. However, this behavior is typically assessed in a
      context in which the subject knows beforehand what he or she has to do. In the
      present experiments, the role of task set was investigated by having the response
      vary randomly from trial to trial. On some trials, a cue signaled the subject to
      respond, and on the remaining trials, another cue signaled the subject to
      withhold a response. Stimulus contrast and temporal overlap between task cue and
      target were manipulated. The effect of a reduction in stimulus contrast was
      sometimes absorbed into the time taken to decode the cue, but critically, other
      times not. These results highlight the theoretical importance of considering task
      set as an essential element in processing, and they undermine the theoretical
      claim that putatively automatic processes are not subject to interference from
      other mental activities.

PMID- 16082803
TI  - Olfactory imagery: a review.
AB  - Olfaction's unique cognitive architecture, the apparently inconsistent evidence
      favoring imagery, and its difficulty of evocation have led some to conclude that
      there is no capacity for olfactory imagery. Using three streams of evidence, we
      examine the validity of this claim. First, self-reports of olfactory imagery can
      resemble those obtained for actual perception. Second, imagining an odor can
      produce effects similar to actual perception. Third, olfactory perception and
      memory-based images can interact. A model of olfactory imagery is then presented
      that utilizes the same systems employed in actual perception, with similar
      constraints. This model is consistent with olfaction's unique information
      processing capacities and can account for previous experimental inconsistencies
      on the basis of difficulty of evocation, a consequence of unstable access to
      semantic information. In sum, the evidence presented here is favorable to the
      existence of an olfactory imagery capacity.

PMID- 16082806
TI  - Linguistically mediated visual search: the critical role of speech rate.
AB  - Recent studies have shown that the presentation of concurrent linguistic context
      can lead to highly efficient performance in a standard conjunction search task by
      the induction of an incremental search strategy (Spivey, Tyler, Eberhard, &
      Tanenhaus, 2001). However, these findings were obtained under anomalously slow
      speech rate conditions. Accordingly, in the present study, the effects of
      concurrent linguistic context on visual search performance were compared when
      speech was recorded at both a normal rate and a slow rate. The findings provided
      clear evidence that the visual search benefit afforded by concurrent linguistic
      context was contingent on speech rate, with normal speech producing a smaller
      benefit. Overall, these findings have important implications for understanding
      how linguistic and visual processes interact in real time and suggest a disparity
      in the temporal resolution of speech comprehension and visual search processes.

PMID- 16082807
TI  - Evidence for gating of direct response activation in the Simon task.
AB  - The Simon effect denotes faster responses when the task-irrelevant stimulus
      position corresponds to the response position than when it does not. Accounts of
      this effect assume that stimulus position automatically activates a spatially
      corresponding response while the correct response is being computed. Yet the
      Simon effect has been found to be reduced after noncorresponding trials. Some
      authors have interpreted these sequential modulations of the Simon effect as
      evidence for a mechanism gating position-based response activation.
      Alternatively, sequential modulations have been explained in terms of feature
      integration processes, which depend upon the fact that different sequences of
      spatial-correspondence conditions covary with different degrees of feature
      overlap between subsequent trials. The present study investigates whether
      sequential modulations of the Simon effect can occur when feature overlap in the
      different conditions is the same. Therefore, a Simon task with four stimulus
      positions and two response positions was used. Sequential modulations of the
      Simon effect were found in trial sequences with constant amounts of feature
      overlap between trials. Although the feature-integration account cannot explain
      this result, it is consistent with the idea of a gating (i.e., cognitive control)
      mechanism.

PMID- 16082808
TI  - The role of selection in generating auditory negative priming.
AB  - The importance of selecting between a target and a distractor in producing
      auditory negative priming was examined in three experiments. In Experiment 1,
      participants were presented with a prime pair of sounds, followed by a probe pair
      of sounds. For each pair, listeners were to identify the sound presented to the
      left ear. Under these conditions, participants were especially slow to identify a
      sound in the probe pair if it had been ignored in the preceding prime pair.
      Evidence of auditory negative priming was also apparent when the prime sound was
      presented in isolation to only one ear (Experiment 2) and when the probe target
      was presented in isolation to one ear (Experiment 3). In addition, the magnitude
      of the negative priming effect was increased substantially when only a single
      prime sound was presented. These results suggest that the emergence of auditory
      negative priming does not depend on selection between simultaneous target and
      distractor sounds.

PMID- 16082809
TI  - Vector averaging of inhibition of return.
AB  - Observers detected targets presented 400 msec after a display containing one cue
      or two to four cues displayed simultaneously in randomly selected locations on a
      virtual circle around fixation. The cue arrangement was completely uninformative
      about the upcoming target's location, and eye position was monitored to ensure
      that the participants maintained fixation between the cue and their manual
      detection response. Reflecting inhibition of return (IOR), there was a gradient
      of performance following single cues, with reaction time decreasing monotonically
      as the target's angular distance from the cued direction increased. An equivalent
      gradient of IOR was found following multiple cues whose center of gravity fell
      outside the parafoveal region and, thus, whose net vector would activate an
      orienting response. Moreover, on these trials, whether or not the targeted
      location had been stimulated by a cue had little effect on this gradient.
      Finally, when the array of cues was balanced so that its center of gravity was at
      fixation, there was no IOR. These findings, which suggest that IOR is an
      aftermath of orienting elicited by the cue, are compatible with population coding
      of the entire cue (as a grouped array for multiple cues) as the generator of IOR.

PMID- 16082810
TI  - The spread of attention to hidden portions of occluded surfaces.
AB  - We report two experiments in which the two-rectangles method of Egly, Driver, and
      Rafal (1994) was used to test whether object-specific attentional cuing
      advantages can spread to hidden portions of occluded objects. Displays began with
      portions of two rectangles hidden by a third, occluding object. One end of one of
      the two rectangles was cued, after which the occluder rotated around its center
      point and target stimuli were presented. In one condition, the occluder was
      removed from in front of the other objects, either by rotating away from them
      (Experiment 1B) or by rotating and then slipping behind them (Experiment 1B). In
      another condition, the occluder first rotated away but then returned to its
      original position. In both experiments, an object-specific cuing advantage
      occurred in the occluder-removed condition for targets that appeared in what had
      been hidden locations of the cued object. No analogous advantage occurred in the
      occluder-returned condition.

PMID- 16082811
TI  - Does the mastery of center-embedded linguistic structures distinguish humans from
      nonhuman primates?
AB  - In a recent Science article, Fitch and Hauser (2004; hereafter, F&H) claimed to
      have demonstrated that cotton-top tamarins fail to learn an artificial language
      produced by a phrase structure grammar (Chomsky, 1957) generating center-embedded
      sentences, whereas adult humans easily learn such a language. We report an
      experiment replicating the results of F&H in humans but also showing that
      subjects learned the language without exploiting in any way the center-embedded
      structure. When the procedure was modified to make the processing of this
      structure mandatory, the subjects no longer showed evidence of learning. We
      propose a simple interpretation for the difference in performance observed in
      F&H's task between humans and tamarins and argue that, beyond the specific
      drawbacks inherent in F&H's study, researching the source of the inability of
      nonhuman primates to master language within a framework built around Chomsky's
      hierarchy of grammars is a conceptual dead end.

PMID- 16082812
TI  - Recognition memory for distractor faces depends on attentional load at exposure.
AB  - Incidental recognition memory for faces previously exposed as task-irrelevant
      distractors was assessed as a function of the attentional load of an unrelated
      task performed on superimposed letter strings at exposure. In Experiment 1,
      subjects were told to ignore the faces and either to judge the color of the
      letters (low load) or to search for an angular target letter among other angular
      letters (high load). A surprise recognition memory test revealed that despite the
      irrelevance of all faces at exposure, those exposed under low-load conditions
      were later recognized, but those exposed under high-load conditions were not.
      Experiment 2 found a similar pattern when both the high- and low-load tasks
      required shape judgments for the letters but made differing attentional demands.
      Finally, Experiment 3 showed that high load in a nonface task can significantly
      reduce even immediate recognition of a fixated face from the preceding trial.
      These results demonstrate that load in a nonface domain (e.g., letter shape) can
      reduce face recognition, in accord with Lavie's load theory. In addition to their
      theoretical impact, these results may have practical implications for eyewitness
      testimony.

PMID- 16082813
TI  - When are viewpoint costs greater for silhouettes than for shaded images?
AB  - Previous studies of object recognition have shown efficient recognition of
      silhouettes, suggesting that much of the information used to recognize objects
      resides in the outline. These studies, however, have used objects that contain
      many components, which provide redundant information. In this study, we examined
      recognition of silhouettes of less-complex objects, so that redundant information
      was reduced. We found that viewpoint generalization costs (the decrement of
      performance when recognizing nonstudied views) were greater for silhouettes than
      for shaded images, even when the same qualitative components were visible in the
      outline of both studied and nonstudied views. Thus, silhouettes do not always
      allow for view generalization as efficiently as do shaded images.

PMID- 16082814
TI  - Attentional preparation based on temporal expectancy modulates processing at the
      perceptual level.
AB  - Research that uses simple response time tasks and neuroimaging has emphasized
      that attentional preparation based on temporal expectancy modulates processing at
      motor levels. A novel approach was taken to study whether the temporal orienting
      of attention can also modulate perceptual processing. A temporal-cuing paradigm
      was used together with a rapid serial visual presentation procedure, in order to
      maximize the processing demands of perceptual analysis. Signal detection theory
      was applied in order to examine whether temporal orienting affects processes
      related to perceptual sensitivity or to response criterion (indexed by d' and
      beta measures, respectively). If temporal orienting implies perceptual
      preparation, we would expect to observe an increase in perceptual sensitivity
      (d') when a target appeared at expected, rather than unexpected, time intervals.
      Indeed, our behavioral results opened the possibility that focusing attention on
      time intervals not only enhances motor processing, as has been shown by previous
      research, but also might improve perceptual processing.

PMID- 16082815
TI  - Contrast and the justification of effort.
AB  - When humans are asked to evaluate rewards or outcomes that follow unpleasant
      (e.g., high-effort) events, they often assign higher value to that reward. This
      phenomenon has been referred to as cognitive dissonance or justification of
      effort. There is now evidence that a similar phenomenon can be found in nonhuman
      animals. When demonstrated in animals, however, it has been attributed to
      contrast between the unpleasant high effort and the conditioned stimulus for
      food. In the present experiment, we asked whether an analogous effect could be
      found in humans under conditions similar to those found in animals. Adult humans
      were trained to discriminate between shapes that followed a high-effort versus a
      low-effort response. In test, participants were found to prefer shapes that
      followed the high-effort response in training. These results suggest the
      possibility that contrast effects of the sort extensively studied in animals may
      play a role in cognitive dissonance and other related phenomena in humans.

PMID- 16082816
TI  - Relations between premise similarity and inductive strength.
AB  - According to the diversity principle, diverse evidence is strong evidence. There
      has been considerable evidence that people respect this principle in inductive
      reasoning. However, exceptions may be particularly informative. Medin, Coley,
      Storms, and Hayes (2003) introduced a relevance theory of inductive reasoning and
      used this theory to predict exceptions, including the nondiversity-by-property
      reinforcement effect. A new experiment in which this phenomenon was investigated
      is reported here. Subjects made inductive strength judgments and similarity
      judgments for stimuli from Medin et al. (2003). The inductive strength judgments
      showed the same pattern as that in Medin et al. (2003); however, the similarity
      judgments suggested that the pattern should be interpreted as a diversity effect,
      rather than as a nondiversity effect. It is concluded that the evidence regarding
      the predicted nondiversity-by-property-reinforcement effect does not give
      distinctive support for relevance theory, although this theory does address other
      results.

PMID- 16082817
TI  - Retroactive interference as a function of degree of interpolated study without
      overt retrieval practice.
AB  - In two experiments, retroactive interference (RI) was examined under conditions
      designed to minimize retrieval-induced inhibition and output interference. In
      Experiment 1, the participants first learned a list of 10 person-location pairs,
      after which they viewed an interpolated list with the same person terms and
      different locations for one, four, or eight cycles. Learning was via a study-only
      method, so that the experimental participants did not perform instructed
      retrieval of the second list before a cued recall test that asked for List 1
      locations only. The experimental participants in Experiment 2 received incidental
      learning instructions and then viewed a list of 20 unrelated words followed by
      another list presented either one or four times; the first two letters of each
      List 1 word were provided on the critical recall test. In both experiments, RI
      occurred and increased with degree of interpolation. The results suggest that RI
      does not require retrieval-induced inhibition.

PMID- 16082818
TI  - Capacity and limits of associative memory in pigeons.
AB  - How much information can a brain store over a lifetime's experience? The answer
      to this important, but little researched, question was investigated by looking at
      the long-term visual memory capacity of 2 pigeons. Over 700 sessions, the pigeons
      were tested with an increasingly larger pool of pictorial stimuli in a two
      alternative discrimination task (incremented in sets of 20 or 30 pictures). Each
      picture was randomly assigned to either a right or a left choice response,
      forcing the pigeons to memorize each picture and its associated response. At the
      end of testing, 1 pigeon was performing at 73% accuracy with a memory set of over
      1,800 pictures, and the 2nd was at 76% accuracy with a memory set of over 1,600
      pictures. Adjusted for guessing, models of the birds' performance suggested that
      the birds had access, on average, to approximately 830 memorized picture-response
      associations and that these were retained for months at a time. Reaction time
      analyses suggested that access to these memories was parallel in nature. Over the
      last 6 months of testing, this capacity estimate was stable for both birds,
      despite their learning increasingly more items, suggesting some limit on the
      number of picture-response associations that could be discriminated and retained
      in the long-term memory portion of this task. This represents the first
      empirically established limit on long-term memory use for any vertebrate species.
      The existence of this large exemplar-specific memory capacity has important
      implications for the evolution of stimulus control and for current theories of
      avian and human cognition.

PMID- 16082819
TI  - Actually, a picture is worth less than 45 words: narratives produce more false
      memories than photographs do.
AB  - Most memory "implantation" studies have elicited false memories by using fake
      narratives. Recently, Wade, Garry, Read, and Lindsay (2002) showed that doctored
      photographs can be used to create false childhood memories in adults. Fifty
      percent of Wade et al.'s sample reported details of taking a childhood hot air
      balloon ride, although they had never been in a balloon. In this experiment, we
      investigated whether photos or narratives influence memory more than the other.
      We exposed subjects to either a fake photograph or a fake narrative of a
      childhood hot air balloon ride. Subjects tried to remember the false event and
      three real events over 1 week. Narratives were more likely to produce false
      memory reports than were photos. We offer a fluency-based account of our results
      and suggest that narratives promote more familiarity in subjects than do
      photographs.

PMID- 16082820
TI  - Sources of confidence judgments in implicit cognition.
AB  - Subjective reports of confidence are frequently used as a measure of awareness in
      a variety of fields, including artificial grammar learning. However, little is
      known about what information is used to make confidence judgments and whether
      there are any possible sources of information used to discriminate between items
      that are unrelated to confidence. The data reported here replicate an earlier
      experiment by Vokey and Brooks (1992) and show that grammaticality decisions are
      based on both the grammatical status of items and their similarity to study
      exemplars. The key finding is that confidence ratings made on a continuous scale
      (50%-100%) are closely related to grammaticality but are unrelated to all of the
      measures of similarity that were tested. By contrast, confidence ratings made on
      a binary scale (high vs. low) are related to both grammaticality and similarity.
      The data confirm an earlier finding (Tunney & Shanks, 2003) that binary
      confidence ratings are more sensitive to low levels of awareness than continuous
      ratings are and suggest that participants are conscious of all the information
      acquired in artificial grammar learning.

PMID- 16082821
TI  - Articulatory suppression and the irrelevant-speech effect in short-term memory:
      does the locus of suppression matter?
AB  - Immediate serial recall for letter sequences was impaired when irrelevant speech
      (IS) was presented throughout stimulus input and a subsequent rehearsal interval.
      This irrelevant-speech effect was eliminated when participants engaged in
      articulatory suppression (repeated articulation of one or more digits) during
      stimulus input but not when suppression occurred during the postinput rehearsal
      period. Also, changing-state suppression (articulation of multiple items)
      impaired the overall level of performance more than did steady-state suppression
      (repetition of a single item), whereas both forms of suppression had the same
      influence on the IS effect. Our results suggest that the locus of suppression
      (during or after stimulus input) may have contributed to discrepant findings in
      the prior literature regarding the influence of articulatory suppression on the
      IS effect. We consider the implications of our findings for three prominent
      models of immediate memory: the working memory model, the object-oriented
      episodic record model, and the feature model.

PMID- 16082822
TI  - A temporally dynamic context effect that disrupts voice onset time discrimination
      of rapidly successive stimuli.
AB  - Across three experiments, voice onset time discrimination along a/ba/-/pa/
      continuum was found to be influenced by the order of presentation of rapidly
      successive stimuli. Specifically, discrimination was disrupted when a relatively
      unambiguous /pa/ syllable was presented before, rather than after, a more
      ambiguous /pa/ or/ba/ syllable. In Experiments 1 and 2, for between-category
      discrimination, this order effect was significant at interstimulus intervals
      (ISIs) below 250 msec, but not at 250 or 1,000 msec. In Experiments 2 and 3, the
      order effect was also significant for within-category discrimination at ISIs
      below 250 msec. In addition, in Experiment 3 this order effect was not diminished
      by provision of performance feedback across eight testing sessions. These
      findings reveal a particular vulnerability of phonological processing in response
      to rapidly successive stimuli and may have implications for mathematical and
      neural models of speech processing of normal and impaired populations.

PMID- 16082823
TI  - [Can we prevent the progression of aortic valve sclerosis and stenosis? The need
      for a prospective, randomized trial].
AB  - Cardiologists long assumed that aortic valve sclerosis/stenosis is a wear-and
      tear, degenerative process; recent studies suggested that lipoproteins can play a
      key role in the development of both sclerosis/stenosis in the aortic valve. Thus,
      sclerosis/stenosis cannot be considered as a simple degenerative process, but on
      the contrary it is complex and involves multiple pathogenetic mechanisms.
      Experimental, clinical and epidemiological data support the link between aortic
      valvulopathy and atherosclerosis: both are caused by inflammation, lipid
      deposition, and accumulation of extracellular bone matrix protein. In non
      randomized clinical studies, hydroxy-methylglutaryl-coenzyme A reductase
      inhibitors minimized the progression of aortic valvulopathy. The major
      pharmacological effect, supposed to underlie the inferred (but still unproven)
      impact of statins on aortic sclerosis/stenosis is plasma cholesterol reduction.
      Lately, retrospective clinical studies supported this hypothesis and suggested a
      key role for statins in delaying the progression of aortic valvulopathy. However,
      the potential favorable effects of statins require confirmation. Prospective
      trials in Canada and Europe are now ongoing (ASTRONOMER--Aortic Stenosis
      Progression Observation Measuring Effects of Rosuvastatin; SEAS--Simvastatin and
      the Ezetimibe in Aortic Stenosis) and will address the use of cholesterol
      lowering drugs in reducing the progression of aortic valve stenosis and in
      improving clinical outcomes.

PMID- 16082824
TI  - [The pacemaker current If: a novel pharmacological target for cardiologists].
AB  - The pacemaker current contributes to endow some types of specialized cells
      (either cardiomyocytes, neurons, or smooth muscle cells) with an intrinsic
      rhythmic activity. In cardiac cells, this current has been named If for "funny
      current" by DiFrancesco, who first described it more than 20 years ago. The
      terminology points to the most peculiar If feature: pacemaker channels activate
      upon membrane hyperpolarization rather than depolarization, opposite to most
      voltage-gated channels. Recently, electrophysiological and molecular data
      demonstrated that f-channels are also present in ventricular cardiomyocytes, and
      become upregulated in cardiac hypertrophy and failure. Misplaced expression
      and/or overexpression of f-channels are a consequence of electrophysiological
      remodeling and, from a clinical point of view, may represent an arrhythmogenic
      mechanism in heart failure, a condition associated with high risk for sudden
      cardiac death. Due to its physiological (and pathophysiological) role and to the
      availability of selective f-channel blockers, If can be considered as a suitable
      therapeutic target for cardiologists.

PMID- 16082825
TI  - [Quantitative evaluation of regional myocardial function using strain and strain
      rate imaging: normal values in pediatric age].
AB  - BACKGROUND: Based on color Doppler methodology, regional myocardial strain rate
      (SR) and strain (epsilon) can now be calculated by comparing local myocardial
      velocity profiles. These deformation data sets may be an important new approach
      to quantify regional function of the left or right ventricle in congenital heart
      disease. The aim of the present study was to provide normal value for epsilon and
      SR in pediatric age. METHODS: We studied 45 healthy subjects (25 males, 20
      females, mean age 11 +/- 6 years, range 4-16 years). For each subject we measured
      regional peak systolic, early and late diastolic E and SR. RESULTS: Left
      ventricular (LV) longitudinal deformations were homogeneous for LV basal, mid and
      apical segments (peak systolic SR -1.9 +/- 0.7 s(-1), systolic epsilon -24 +/-
      8%). Longitudinal SR and epsilon values were significantly higher in the right
      ventricle, compared with LV walls, and were maximal in the mid part of the right
      ventricle free wall (peak systolic SR -3.4 +/- 0.9 s(-1), systolic epsilon -35 +/
      5%). The LV systolic and diastolic SR and epsilon values were higher for
      deformations in the radial direction compared with the longitudinal direction
      [radial peak systolic epsilon 55 +/- 6% vs longitudinal peak systolic epsilon (
      )24 +/- 8%, p < 0.0001; radial peak early diastolic epsilon (-)40 +/- 15% vs
      longitudinal peak early diastolic epsilon 17.22 +/- 7%, p < 0.0001; radial peak
      systolic SR 2.7 +/- 0.5 s(-1) vs longitudinal peak systolic SR (-)1.9 +/- 0.7 s(
      1); radial peak early diastolic SR (-)6.2 +/- 1.5 s(-1) vs longitudinal peak
      early diastolic SR 2.24 +/- 1.2 s(-1), p < 0.0001]. CONCLUSIONS: This study
      provides normal values for epsilon/SR in the largest published series of normal
      healthy children using a high frame rate (> or = 200 frames/s) and a commercially
      available software.

PMID- 16082826
TI  - [Guidelines for percutaneous coronary interventions].

PMID- 16082827
TI  - [Contribution of surgeons of the Saint Petersburg medical academy of postgraduate
      education to the development of national surgery and collaboration with the
      journal Vestnik Khirurgii im. I. I. Grekova].

PMID- 16082828
TI  - [Aleksandr Vasilievich Vishnevsky (1874-1948)].

PMID- 16082829
TI  - [Surgical treatment of local-expanded forms of thyroid carcinoma].
AB  - An analysis of surgical treatment of 377 patients with advanced thyroid carcinoma
      is presented. The work included 82 combined, 90 expanded and 218 palliative
      operations (as well as 68 shave-resections). In 56 cases surgical interventions
      were two-or three-staged. This approach improved the immediate results and did
      not change the long-term results of treatment. It was shown that surgical
      treatment in advanced thyroid carcinoma gave good results in the majority of
      cases (recovery or long-term palliation). Combined and expanded operations were
      non effective in anaplastic thyroid carcinoma. In well-differentiated thyroid
      carcinoma the 10-year survival was noted in 70.2% of patients.

PMID- 16082830
TI  - [Surgical treatment of diseases and injuries of the colon].
AB  - The results of treatment of 330 patients with complicated diseases and traumas of
      the colon were analyzed. The treatment included primary resection of the colon
      with the formation of separate double-trunked (220 patients) and single-trunked
      (110 patients) colostomies. Postoperative complications were noted in 26.4% of
      cases. The formation of separate double-trunked colostomies allowed facilitation
      of surgical rehabilitation of the colostomy patients. The technical elements of
      formation of separate double-trunked colostomies after resection of the colon are
      described.

PMID- 16082831
TI  - [Frontal resection as a means of decision for surgical treatment of rectum
      cancer].
AB  - The work has been devoted to the improvement of methods of surgical treatment of
      cancer of the rectum. The possibilities to perform organ-saving operations in
      treatment of cancer of the rectum are discussed. An analysis of treatment of 351
      patients with cancer of the rectum has shown that frontal resection of the rectum
      is possible in more than 40% of such patients since such interventions save the
      function of the rectum more completely. New methods of preoperative preparation
      of the patients are described as well as the application of the improved methods
      of surgical interventions.

PMID- 16082832
TI  - [Syndrome of compression of the celiac trunk of the abdominal aorta in adults].
AB  - The article presents results of examinations and surgical treatment of 300
      patients aged from 19 through 72 years with the syndrome of compression of the
      celiac trunk of the abdominal aorta. Under study were the symptoms and features
      of the clinical course as well as the possibilities of diagnosis with the help of
      ultrasonic duplex scanning and aortography. The principal method of treatment of
      this syndrome is thought to be operative decompression of the celiac trunk
      resulting in the reestablished hemodynamics in this vessel and in recovery of the
      greatest part of the patients.

PMID- 16082833
TI  - [Hemodynamic characteristics and surgical treatment of varicose disease with
      primary involvement of deep vein valves].
AB  - Results of clinical examinations and ultrasonic duplex scanning of the venous
      system of the lower extremities performed in 31 patients with the varicose
      disease were analyzed. The disease developed due to the primary valve
      insufficiency of the profound veins. This form is characterized by total-subtotal
      refluxes of blood along the subcutaneous veins, multiple lesions of the perforant
      veins, the presence of the hemodynamically valuable blood refluxes in the
      profound and muscle veins. The hemodynamic parameters of blood flow and the
      technology of surgical treatment of the deep, superficial, perforant and muscle
      blood refluxes are shown allowing to restore the quality of life in 76.7% of the
      patients and considerately improve it in 23.3%.

PMID- 16082834
TI  - [Pathogenetical features of the first period of trauma disease with acute
      respiratory insufficiency].
AB  - The pathogenetical features of acute respiratory insufficiency (ARI) were studied
      as a clinical form of the first period of the trauma disease (TD)--the period of
      acute impairments of the important for life functions (the first 8-12 h after
      trauma). In 17 casualties with a severe combined trauma the severity of the first
      period of the disease depended on the ARI caused by a serious injury of the chest
      not accompanied by a direct injury of the heart. It was shown that ARI is an
      independent clinical form of the first period of TD. The indices of the systemic
      hemodynamics in ARI are within the limits of the normal values. ARI resulting
      from the "primary" injury of the lungs results in a decreased delivery of oxygen
      to the tissues and of its consumption. When ARI takes place during the first
      period of TD the metabolic function of the lungs is sharply suppressed and
      pronounced endotoxemia is observed.

PMID- 16082835
TI  - [Pathobiochemical aspects of surgical strategy in treatment of fractures of the
      tubular bones in combined traumas].
AB  - The article is devoted to pathobiochemical substantiation of the surgical
      strategy in treatment of fractures of the tubular bones in combined traumas. It
      was found that fractures of the tubular bones are a source of endogenous
      intoxication. Osteosynthesis facilitates the elimination of its manifestations.
      Stable osteosynthesis shortening the period of posttraumatic stress is a powerful
      adaptogenic factor. Optimization of the process of adaptation influenced by
      osteosynthesis is a result of blocked stream of pathological afferentation after
      fixation of the fragments. The performing of osteosynthesis facilitates quicker
      normalization of biochemical indices and transition of the casualty's organism to
      the phase of long-term adaptation. It explains the urge to early eliminate the
      dangerous for life conditions, to liquidate the sources of endotoxicosis and
      excessive afferent effects of the pathological foci which can often be caused by
      fractures of the tubular bones.

PMID- 16082836
TI  - [Errors and complications in treatment of the Erlacher-Blount disease by the
      method of perosseous osteosynthesis].
AB  - The author has made an analysis of results of treatment of 116 patients. A
      classification of recurrences of the disease is given. Possible errors of the
      treatment and complications are described as well as the measures of their
      prevention.

PMID- 16082837
TI  - [The oxygen-transport function of blood in reconstructive operations on the aorto
      femoral segment and application of high molecular hydroxyethyl starch].
AB  - The prospective randomized investigation included 71 patients with obliterating
      atherosclerosis of the lower extremities with chronic ischemia. Planned
      operations of aorto-bifemoral shunts were made. Patients of the first group
      (n=43) were treated by infusion therapy including solutions of colloids and
      crystalloids. In the second group a solution of high molecular hydroxyethyl
      starch was used in addition to colloids and crystalloids. Transfusion of the
      allogenic components of blood was made in the both groups according to the
      indications. The parameters of the oxygen-transport function of blood were
      studied before initial narcosis, under conditions of general anesthesia before
      the beginning of operation, in 60 minutes of reperfusion after finishing the
      aorto-femoral shunting, and in a day after operation. It was shown that using the
      solution of high molecular hydroxyethyl starch promoted the elevated level of the
      delivery and consumption of oxygen as compared with the standard infusion
      transfusion therapy which is explained by the predominantly hemodynamic component
      of the oxygen transport.

PMID- 16082838
TI  - [A new method of surgical treatment of morbid obesity].
AB  - The article presents results of surgical treatment of 48 patients with morbid
      obesity and concomitant metabolic disorders in the clinic of Faculty Surgery of
      the Bashkir state medical university. A new means of vertical gastroplasty is
      described allowing to prevent the early development of reflux-esophagatis and to
      reduce the number of postoperative complications. Stable reduction of the body
      mass was obtained in 7 patients with morbid obesity by using the method in the
      clinical practice.

PMID- 16082839
TI  - [A method of suturing the operation wound in patients with obesity].
AB  - A method of multistoried closing the wound with the help of 2-4 adapting
      horizontal mattress sutures onto the subcutaneous fatty tissue and one suture
      onto the skin was used in 58 patients with the III degree of obesity for suturing
      the postoperative wound in the area of the frontal abdominal wall. No specific
      complications resulting from the used technique of suturing the wound were noted.
      Long-term results of treatment showed a good cosmetic effect.

PMID- 16082840
TI  - [Surgical treatment of bilateral hernias of the inguinofemoral area].
AB  - Consecutive surgical treatment of bilateral hernias leads to the appearance of
      recurrences in 67% of the operated patients. An important etiological moment of
      the appearance of the repeated, by turns recurrences in the two-steps elimination
      of a bilateral inguinal hernia is the symptom of tension and pulling the lateral
      muscles of the abdomen from one side to the other. The proposed method of a one
      step surgical treatment, using the suprapubic access by the developed technique,
      allows reduction of recurrences to 2.2%.

PMID- 16082841
TI  - [Treatment of patients with combined burn strictures of the esophagus and
      stomach].
AB  - The authors made an analysis of their experiences with treatment of 52 patients.
      The algorithm of examinations and treatment depending on the character of the
      injury of the esophagus and stomach is described. Positive results were obtained
      in 90% of the patients.

PMID- 16082842
TI  - [Substitution of a lengthy defect of the ureter for the vermiform appendix].
AB  - The authors share their experiences with the substitution of the ureter for the
      appendix in three patients. In two of them the lengthy constriction of the pelvic
      portion of the ureter resulted from postirradiation alterations, in the other-
      from a gunshot wound of the lumbar area. The sufficient length and diameter of
      their appendix on a mobile mesentery allowed its being used for the substitution
      of the ureter. The results of operations were successful and without
      postoperative complications in all cases.

PMID- 16082843
TI  - [Postpneumonectomy syndrome in a patient with lung cancer].

PMID- 16082844
TI  - [Primary-multiple synchronous cancer of the stomach and colon in elderly
      patients].

PMID- 16082845
TI  - [Dystopia of the gall bladder in a patient with hepatocellular carcinoma].

PMID- 16082846
TI  - [Foreign body of the common bile duct].

PMID- 16082847
TI  - [Successful surgical correction of aneurysm of the ascending aorta with
      insufficiency of the aortal valve and concomitant coronary pathology in a patient
      with a single kidney].

PMID- 16082848
TI  - [On the question of terminology of consequences of a compression trauma and acute
      impairment of the blood flow in the extremities (apropos of the article by I. P.
      Dudanov et al. "On a united approach to terminology of consequences of a
      compression trauma and acute disturbance of the main blood circulation". -Vestn.
      Khir.--2004.--No 1.--P. 108].

PMID- 16082849
TI  - [Nikolai Vasil'evich Sklifosovskii (1836-1904)].

PMID- 16082850
TI  - [The history of endocrine surgery in Russia].

PMID- 16082851
TI  - [Surgical diseases in patients with HIV-infection].

PMID- 16082852
TI  - [Injuries to the colon and rectum in peace-time].

PMID- 16082853
TI  - Birth rights and rituals in rural south India: care seeking in the intrapartum
      period.
AB  - Maternal morbidity and mortality are high in the Indian context, but the majority
      of maternal deaths could be avoided by prompt and effective access to intrapartum
      care (WHO, 1999). Understanding the care seeking responses to intrapartum
      morbidities is crucial if maternal health is to be effectively improved, and
      maternal mortality reduced. This paper presents the results of a prospective
      study of 388 women followed through delivery and traditional postpartum in rural
      Karnataka in southern India. In this setting, few women use the existing health
      facilities and most deliveries occur at home. The analysis uses quantitative
      data, collected via questionnaires administered to women both during pregnancy
      and immediately after delivery. By virtue of its prospective design, the study
      gives a unique insight into intentions for intrapartum care during pregnancy as
      well as events following morbidities during labour. Routine care in the
      intrapartum period, both within institutions and at home, and impediments to
      appropriate care are also examined. The study was designed to collect information
      about health seeking decisions made by women and their families as pregnancies
      unfolded, rather than trying to capture women's experience from a retrospective
      instrument. The data set is therefore a rich source of quantitative information,
      which incorporates details of event sequences and health service utilization not
      previously collected in a Safe Motherhood study. Additional qualitative
      information was also available from concurrent in-depth interviews with pregnant
      women, their families, health care providers and other key informants in the
      area. The level of unplanned institutional care seeking during the intrapartum
      period within the study area was very high, increasing from 11% planning
      deliveries at a facility to an eventual 35% actually delivering in hospitals. In
      addition there was a significant move away from planned deliveries with the
      auxiliary nurse midwive (ANM), to births with a lay attendant or dai. The
      proportion of women who planned for an ANM to assist was 49%, as compared with
      the actual occurrence, which was less than half of this proportion. Perceived
      quality of care was found to be an important factor in health seeking behaviour,
      as was wealth, caste, education and experience of previous problems in pregnancy.
      Actual care given by a range of practitioners was found to contain both
      beneficial and undesirable elements. As a response to serious morbidities
      experienced within the study period, many women were able to seek care although
      sometimes after a long delay. Those women who experienced inadequate progression
      of labour pains were most likely to proceed unexpectedly to a hospital delivery.

PMID- 16082854
TI  - Significant effects of birth-related biological factors on pre-adolescent
      nutritional status among rural Sundanese in West Java, Indonesia.
AB  - The Sundanese inhabiting West Java, the second largest ethnic group in Indonesia,
      are characterized by a high prevalence of child malnutrition, together with high
      fertility. Based on an anthropometric measurement and interview survey of 310
      children aged 5-12 years in a rural Sundanese village, this study examined the
      relative significance of the effects of eight biological, eight socioeconomic
      status (SES) and four health behavioural factors on their Z scores for height-for
      age (HAZ) and weight-for-age (WAZ) in particular. Three biological factors, i.e.
      birth interval, birth weight and mother's body weight, and one SES factor, i.e.
      mother's occupation, were selected as the predictors of the two Z scores by
      regression analysis, indicating more significant effects of the biological
      factors than the other factors. This pattern is judged to occur in less-developed
      and high-fertility populations. Since these two Z scores were worse in the
      subject children than in the under-5-year-old children from the same village,
      more attention should be paid to the long-lasting effects of birth-related
      biological factors up to pre-adolescent ages, as an insufficient nutritional
      status tends to damage growth and health in adolescence and adulthood.

PMID- 16082855
TI  - Changing patterns of social variation in stature in Poland: effects of transition
      from a command economy to the free-market system?
AB  - The aim of this analysis was to examine the effects on stature in two nationally
      representative samples of Polish 19-year-old conscripts of maternal and paternal
      education level, and of degree of urbanization, before and after the economic
      transition of 1990. Data were from two national surveys of 19-year-old Polish
      conscripts: 27,236 in 1986 and 28,151 in 2001. In addition to taking height
      measurements, each subject was asked about the socioeconomic background of their
      families, including paternal and maternal education, and the name of the locality
      of residence. The net effect of each of these social factors on stature was
      determined using four-factor analysis of variance. The secular trend towards
      increased stature of Polish conscripts has slowed down from a rate 2.1 cm per
      decade across the period 1965-1986 to 1.5 cm per decade between 1986 and 2001. In
      both cohorts, mean statures increase with increasing size of locality of
      residence, paternal education and maternal education. The effect of each of these
      three social factors on conscript height is highly significant in both cohorts.
      However, the effect of maternal education has increased substantially while that
      of size of locality of residence and paternal education diminished between 1986
      and 2001. These results imply that the influence of parental education on child
      growth cannot be due solely to a relationship between education and income, but
      is also perhaps a reflection of household financial management which benefits
      child health and growth by better educated parents, regardless of level of
      income. In addition they suggest that, irrespective of whether there are one or
      two breadwinners in the family, it is the mother, more so than the father, who is
      principally responsible for the extent to which such management best favours
      child health and growth. The asymmetry between the importance of maternal as
      against paternal education for child growth, clearly seen in the 1986 cohort,
      became more accentuated in 2001, after the abrupt transition from a command to a
      free-market economy in the early 1990s.

PMID- 16082856
TI  - Consistent condom use dynamics among sex workers in Central America: 1997-2000.
AB  - The paper aims to provide evidence on consistent condom use dynamics among sex
      workers in Central America between 1997 and 2000, and to examine the most
      important predictors of use behaviour important for policy and programme
      interventions in the region. Data on 3500 sex workers, 1500 from 1997 and 2000
      from the year 2000, were analysed. The samples represented sex workers in low
      socioeconomic neighbourhoods who met their clients at known sex establishments or
      by the roadside. Sex workers were more likely to have used condoms consistently
      in 2000 than in 1997 (Odds Ratio (OR) = 1.4, p < or = 0.05). Sex workers who
      discussed condoms with their partners or lovers used them consistently with all
      clients more than those who did not (OR = 1.3, p < or = 0.10). Knowledge of
      condom advantages had a positive influence on consistent use. Sex workers who
      reported using condoms to prevent pregnancy or STDs used them consistently with
      all clients more than those who did not (OR = 1.2, and 1.3 respectively, p < or =
      0.10). The source of condoms is an important predictor of consistent condom use.
      Sex workers who bought condoms from health establishments or from brothels used
      them consistently more than those who did not (both OR = 1.3, p < or = 0.10, and
      p < or = 0.05, respectively). Self-efficacy had a positive effect on consistent
      condom use. Sex workers who reported that they would use condoms even if clients
      offered to pay more for unprotected sex used them consistently with all clients
      more than those who did not (OR = 18, p < or = 0.001). The findings suggest that
      having condom skill is positively related to condom use. Sex workers who had all
      four skills used condoms more consistently than those who had none (OR = 1.6, p <
      or = 0.01). In order to increase consistent condom use and avert more incidences
      of HIV/AIDS and other STIs, programme interventions need to use the most
      efficient way to provide quality information, and provide repeated training on
      condom negotiation and use skills to sex workers.

PMID- 16082857
TI  - Sterilization and union instability in Brazil.
AB  - Brazilian women rely on sterilization as the main source of birth control.
      Sterilization has been one of the causes of the steep decline in fertility in
      Brazil, at least since the second half of 1970. It is hypothesized that
      understanding couples' relationships might be key to explaining this high rate of
      female sterilizations. Possible reasons for the higher level of fertility among
      women in unstable unions than among women in stable ones could be the less
      effective use of contraceptive methods, or that women in unstable unions tend to
      use less effective or reversible contraceptive methods. In this paper discrete
      time modelling of the timing of sterilization according to union histories is
      presented. The analysis uses the calendar data of the 1996 Brazilian DHS. It is
      shown that women in second or higher order unions have a lower risk of
      sterilization. This result should be taken into account in the analysis of the
      determinants of female sterilization in Brazil.

PMID- 16082858
TI  - Applying a data duplication technique in linear regression analysis of waiting
      time to pregnancy.
AB  - This analysis demonstrates the application of a data duplication technique in
      linear regression with censored observations of the waiting time to third
      pregnancy ending in two outcome types, using data from Malaysia. The linear model
      not only confirmed the results obtained by the Cox proportional hazards model,
      but also identified two additional significant factors. The method provides a
      useful alternative when Cox proportionality assumption of the hazards is
      violated.

PMID- 16082859
TI  - Marital coitus across the life course.
AB  - It remains unclear whether the frequency of marital coitus does in fact decline
      universally across the life course, what shape that decay normally takes, and
      what best accounts for it: increasing marriage duration, women's age or age of
      their partners. Using cross-sectional Demographic and Health Survey (DHS) data of
      91,744 non-abstaining women in their first marriage, a generalized linear model
      is used to determine if there is a consistent pattern in the life course pattern
      of degradation in the frequency of marital coitus. Datasets were drawn from
      nineteen countries in Asia, Africa and the Americas. Use of very large samples
      allows proper disentangling of the effects of women's age, husband's age and
      marital duration, and use of samples from multiple countries allows consideration
      of the influence of varied prevailing fertility regimes and fertility-related
      practices on life course trajectories. It is found that declining coital
      frequency over time seems a shared demographic feature of human populations, but
      whether marriage duration, wife's age or husband's age is most responsible for
      that decline varies by country. In many cases, coital frequency actually
      increases with women's age into their thirties, once husband's age and marriage
      duration are taken into account, but in most cases coital frequency declines with
      husband's age and marital duration.

PMID- 16082860
TI  - The frequency and effecting factors of consanguineous marriage in a group of
      soldiers in Ankara.
AB  - This cross-sectional study was carried out to investigate the frequency of
      consanguineous marriage in a group of army conscripts in Ankara and the factors
      affecting this. Of 4153 soldiers, 387 were married. The rate of marriage between
      first cousins was found to be 19.1%, and the overall rate of consanguineous
      marriage was 24.1%. Consanguineous marriage was found to be significantly
      prevalent among soldiers who were born in and still living in the Eastern region;
      among those who lived in villages; among those whose parents as well as
      themselves had low educational levels; and among those whose marriages were
      arranged by their families. Neither the payment of bride-price nor the presence
      of consanguinity between parents was a significant factor for consanguineous
      marriage. In addition, the age of the soldier and the age at marriage were
      significantly lower among soldiers married to first cousins than among soldiers
      whose marriages were not consanguineous.

PMID- 16082861
TI  - Medical liability issues in cosmetic and plastic surgery.
AB  - The liability issues may involve some turf battles between the specialties
      because of the possibility of one specialty trying to institute lawsuits through
      patients against the other specialty in order to drive the competition out of
      business. Each cosmetic surgical procedure has liability issues particular to the
      surgery but there are many common issues that involve a number of different
      procedures. These include: Failure to maintain adequate patient rapport. Failure
      to give proper informed consent. Failure to obtain information on significant
      past medical history. Performing procedure not requested. Breaching the standard
      of care in the performance of the surgery or procedure. Failure to diagnose and
      treat a complication in a timely fashion. Expert witness misrepresentations. This
      paper analyzes the various aspects of liability in the plastic/cosmetic surgery
      field and attempts to aid the physician in preventing or resolving some of these
      problems.

PMID- 16082862
TI  - Witness evidence: can it be trusted?
AB  - Basic statistical principles are often widely misunderstood (and often
      mistrusted) by many members of the public at large. It comes as no shock that
      this also applies to legal practitioners. If there is an ignorance of the
      intricacies of statistics by the judiciary and counsel, it is not surprising that
      erroneous conclusions based on the evidence have arisen. These have even been
      afforded their own special designation as 'fallacies', including those of both
      the prosecutor and defence. Whether or not the underlying mathematics is fully
      understood, it is essential that practitioners can correctly interpret
      information provided by witnesses, expert or otherwise. This article provides one
      contribution in that direction toward cases that specifically involve medical
      situations. It considers some of the more outrageous conclusions made, and
      accepted, in several high profile cases and considers the evidence more
      carefully. The challenge is to be able to determine the likelihood that any
      assertion made is actually true from a statistical point of view. Examples of how
      to make this determination are provided, including the all-important notion of
      conditional probability.

PMID- 16082863
TI  - Admissibility of scientific evidence in courts.
AB  - In its 1993 Daubert v. Merrell Dow opinion, the United States Supreme Court
      articulated an entirely new set of criteria for the admissibility of scientific
      expert testimony. In its 1999 Kumho Tire v. Carmichael opinion, the Court
      extended Daubert's general holding to include non-scientific expert testimony as
      well. Most modem litigation relies upon the testimony of experts and this
      testimony can play a dispositive role in litigation. In all parts of the case,
      liability, causation and damages, lawyers are winning cases by using newly
      available techniques, suggested by Daubert and Kumho Tire, to exclude the expert
      testimony that links damages to the act or omission for which their client has
      been found liable. Our article contains medico-legal analysis of cases, beginning
      in the application of Israeli case law which discusses the Daubert Court's
      holding and explaining the scientific principles that the Court cites. The
      Daubert introduction links to a brief discussion of the Court's 1999 extension of
      Daubert to non-scientific testimony. We present a two-part model for evaluating
      the admissibility of scientific evidence--internal and external--in the Israeli
      courts. The internal examination of the scientific evidence evaluates its
      reliability by examining the content of the evidence and by checking that its
      conclusions correspond to the research methods of scientific literature. The
      court also has to review the abilities and skills of the expert witness. If the
      evidence passes the internal evaluation, the court will apply an external
      evaluation by examining whether the scientific evidence coincides with the other
      evidence presented to the court according to the specific rules of the law
      applied to the particular case.

PMID- 16082864
TI  - The use and control of heel prick blood samples.
AB  - The human body is assuming new meanings and value. When tissue, such as hair,
      blood and saliva is subjected to DNA analysis, detailed intimate information can
      be revealed about a person that may predict information about behavioural traits
      and future disorders. Such genetic information may lead to the development of
      beneficial therapeutic treatments, but it may also lead to employment or
      insurance discrimination. Human tissue is commonly used by law enforcement
      agencies to detect perpetrators of crimes and to identify corpses. There are many
      sources of such tissue samples. One is from samples routinely collected from
      newborn babies for a test known as the "Guthrie test" or heel prick test. At
      about two days of age the child's heel is pricked and the resultant drops of
      blood are applied to filter paper attached to a test card. This is dried and
      analysed and, in New Zealand, the cards are stored indefinitely. The potential
      range of research purposes using such blood samples is increasing, and expanding
      markets have increased their value. This paper considers the status of the
      samples in light of recent developments in New Zealand and suggests appropriate
      approaches for retention and further use of the samples, or third party access to
      them.

PMID- 16082865
TI  - Strict vegan, low-calorie diet administered by caregiving daughter to elderly
      mother--is this elder abuse?
AB  - We present a case in which a 40 year old woman, who was the primary care-giver of
      her 78 year-old mother, provided a strict vegan diet which caused the mother
      severe malnutrition. The mother was hospitalized with severe functional
      deterioration and, while eating a proper diet during hospitalization, gained
      weight and her condition improved. The case was reported to the Welfare Officer
      and the mother was released under the supervision of the Welfare Officer. Cases
      of severe malnutrition and even death of infants who were fed a strict vegan diet
      have been reported. This case raises some ethical and legal issues. Should a
      guardian or a caregiver be allowed to make decisions regarding the way of life
      and medical treatment of the person in his/her charge which are likely to
      endanger that person's health and when is it appropriate for society to intervene
      in individual freedom? The paper includes a review of some reported cases of
      child and elder abuse or neglect which illustrate these issues.

PMID- 16082866
TI  - Governmental studies on medical malpractice: the implications of rising premiums
      for healthcare and the allocation of health resources.
AB  - The United States may or may not be facing a "malpractice crisis" which can
      result in a loss of quality of medical care in certain specialties by virtue of
      non-performance or the exiting of certain physicians from certain high-risk
      specialties due to increases in premiums. Various studies have been performed by
      various governmental agencies on a federal level in the United States. The
      Department of Legal Medicine, part of the Armed Forces Institute of Pathology,
      began collecting veteran's affairs medical malpractice claims data and extracting
      information from the analysis from medical records and associated documents.
      During the 1993 fiscal year, 801 medical malpractice claims were filed against
      the Department of Veteran's Affairs. The Department of Veteran's Affairs had
      approximately 125,000 hospital discharges and 26 million outpatient visits during
      the same time period. The rate of claims per hospital discharge was less than 1/
      1000 hospital patient discharges (.864/1000). Subsequent to that report, several
      other reports have been issued including a report on medical malpractice
      insurance generated by the General Accounting Office in 2003, some ten years
      later. More recently, a report of medical malpractice having implications on
      rising premiums on and access to health care generated by the General Accounting
      Office was released in August of 2003. This paper will demonstrate areas of
      concern with regard to the area of medical malpractice as well as incidence of
      medical malpractice and claims upon the insurance industry, medical specialties
      and the impact upon the community generally in the United States.

PMID- 16082867
TI  - Deference or deliberation: rethinking the judicial role in the allocation of
      healthcare resources.
AB  - The development of strategies by which healthcare resources are explicitly
      rationed has created significant challenges for many governments. In particular,
      those undertaking allocative decisions may struggle to establish sufficient
      legitimacy to enable them to make choices which are morally and politically
      controversial without generating distrust and resistance, which could jeopardise
      the effectiveness of the decision-making regime. This article considers possible
      means of addressing this difficulty from the perspective of public law. The
      mechanism which is currently favoured, most clearly seen in the UK, is to
      establish regulatory agencies which apply scientific and social-scientific
      methodologies to priority-setting questions. This has not been entirely
      successful. Accordingly, the article will propose a more developed role for
      courts, which can require that reasoned, relevant justifications for allocative
      choices are offered and thus provide a foundation for broad public deliberation
      on rationing. However, in order to fulfil such a function, the judiciary will
      need to modify its traditionally deferential stance on issues of this type. South
      African and Canadian cases illustrate how such a change may come about.

PMID- 16082868
TI  - The impact of immigration on health systems: a legal analysis from a three
      country perspective.
AB  - The focus of this paper will be on how health care systems in three countries,
      Malaysia, South Africa and the United States, are responding to the health needs
      of immigrants with a strong focus on the legal aspects of the respective national
      responses. The Malaysia portion emphasizes legal immigration and analyses as to
      how the country's Ministry of Health and the delivery system itself is responding
      to the demands of immigrant's health. In the context of South Africa, the paper
      explores implications of the South African Constitution, which establishes a
      right to access health care, and explores whether such a right can be extended to
      non-citizens, or can be tempered by economic constraints. In the American
      discussion the focus is on whether publicly supported health care programs can be
      accessed to provide coverage for undocumented residents, and highlights recent
      constraints in using government monies in this area.

PMID- 16082869
TI  - The European Court of Justice and working time in the health care sector:
      relevance to the Czech Republic.
AB  - In a recent court ruling, the European Court of Justice concluded that a Member
      State violated the European Directive on working time. The issue concerned the
      meaning of working time as defined by the Directive. It appeared that the time an
      employee is present and available at the workplace, with a view to providing his
      professional services, had to be considered as working time. That conclusion may
      affect the organisation of health services in other Member States, such as the
      Czech Republic.

PMID- 16082870
TI  - Reprogenetics and pharmacogenetics: in whose best interests?
AB  - Reprogenetics involves embryonic pre-implantation genetic diagnosis, provoking
      controversy over the creation of saviour siblings, eugenics and genetic
      enhancement. It will soon ascertain pharmacogenetic susceptibilities.
      Pharmacogenetics impacts upon public health initiatives underpinned by resource
      allocation constraints in that genetic epidemiological studies assist in
      administering health care resources and public health strategies. Knowing how
      likely sections of the population are to develop specific medical conditions so
      that lifestyle and environmental factors influencing these conditions can be
      targeted has the potential to save public money and improve public health.
      Aligning population groups with genetic susceptibilities with specific
      medications would enable cost-effective prescribing. Reprogenetics and
      pharmacogenetics also possess great commercial potential for nation states and
      biotechnology companies. Hence ethical legal safeguards for members of the public
      whose reproductive or genetic tissue is a research or health care resource are
      essential. Both legal measures such as informed consent and mechanisms for
      including the public in policy decisions over reprogenetics and pharmacogenetics
      must be rethought to ensure that they provide protection rather than function as
      rubber stamps which preclude deeper inquiry into justifications of projects.

PMID- 16082871
TI  - Balancing the need for innovative drugs while providing lower cost alternatives
      to consumers: Hatch-Waxman reviewed.
AB  - There is a long continuum of differing positions amongst academia, the private
      sector, and the public sector in determining the appropriate balance between
      providing incentives to both innovator drug companies and generic drug
      manufacturers, while at the same time also protecting legitimate patent rights.
      Juxtaposed to these issues is the fact that the cost of biomedical research is
      enormous and it continues to grow as the government seeks to provide for the
      health and welfare of a public that not only seeks therapeutic medicine and
      medical care when sick, but also wants prophylactic and diagnostic products.
      Furthermore, personalized medicine, resulting from the advances in functional
      genomics and new and increased use of lifestyle drugs providing therapies ranging
      from male pattern baldness to erectile dysfunction, is indicative of the ever
      increasing expectations for a greater range of products. The debate then is not
      only how to make such products available but also how to make them affordable.
      With more than 500 drug patents scheduled to expire between 2004 and 2009 (with
      26 of these drugs accounting for more than 38 billion dollars in sales annually),
      the stakes are high, for not only the generic and brand name manufacturers, but
      also for the consumer.

PMID- 16082872
TI  - The effect of confidence and method of questioning on eyewitness testimony.
AB  - Very often eyewitnesses are perceived as being accurate due to the confidence in
      the accuracy of their own testimony. The confidence displayed by an eyewitness
      may possibly be increased by the method of questioning used by legal
      professionals and police. The present study examines the confidence-accuracy
      relationship and the effect the method of questioning (open-ended versus closed
      ended questions) may have on the confidence of eyewitnesses. The sample of 412
      respondents consisted of scholars (11 to 14-year-olds), university students, the
      public and Police College students. A significant relationship between memory
      accuracy and confidence was found for more than 70% of the questions. Closed
      ended questions provided a significantly higher rate of accuracy than open-ended
      questions. A significantly larger proportion of respondents to the closed-ended
      questions were more confident about their answers than those who responded to the
      open-ended questions.

PMID- 16082873
TI  - Some problems challenging the UK's Human Fertilisation and Embryology Authority.
AB  - The UK's Human Fertilisation and Embryology Authority (hereafter the HFEA) is a
      regulatory body facing growing pressures and difficulties. Like any regulatory
      body, it faces the challenge of regulating with sufficient expertise, legitimacy,
      and contemporaneity. This challenge is, however, exacerbated by the fact that it
      seeks to regulate some of the most controversial and rapidly changing
      technologies of our time. Its decisions and jurisdictional assumptions face
      increasing challenge. In addition to the multitude of cases brought against it,
      the HFEA's actions recently led a House of Commons Select Committee to pointedly
      declare that "democracy is not served by unelected quangos (quasi-autonomous non
      governmental organizations) taking decisions on behalf of Parliament". While
      endorsing the general need to review the legislation under which the HFEA
      operates (the Human Fertilisation and Embryology Act 1990), this paper will argue
      that the HFEA was correct in interpreting its jurisdiction to encompass the
      technique used to produce Dolly the sheep. This paper thereby defends the key
      feature of the approach of the House of Lords in the recent case of R (Bruno
      Quintavalle on behalf of the ProLife Alliance) v Secretary of State for Health
      [2003] UKHL 13.

PMID- 16082874
TI  - A new framework for facilitating decisions on death and dying.
AB  - The troubling public, moral and legal issues surrounding questions of death and
      dying need a new focus on the virtues of compassion and respectfulness, on a
      better understanding of a person as someone who has deep emotional, spiritual,
      and social aspects and needs, and whose body is more than "physical machine," but
      is "lived body" which gives persons the capacity to act in the world and to feel
      and suffer deeply. Western medicine needs to re-humanize death; physicians need
      to see themselves as "assisting" persons in dealing with health, life and death
      in the context of being able to assert their values and beliefs and to realize
      their goals. Western medicine's concepts of 'benefit' and 'harm,' are too narrow,
      as is their fight to 'preserve life' at all costs. Finally, the present approach
      to death and dying, except for the Hospice movement, neglects the patient's
      emotional, psychological, social, and existential suffering.

PMID- 16082875
TI  - Ethical considerations within clinical research with special focus upon clinical
      drug trials.

PMID- 16082876
TI  - Pharmacists & pharmaceutical manufacturers: some ethical considerations.

PMID- 16082877
TI  - [Manual or rotary root canal preparation? Nickel-titanium or stainless steel?
      Review of the literature].
AB  - The aim of this review was to determine the advantages and disadvantages of
      rotative nickel-titanium endodontic instruments compared with stainless steel
      manual instruments on the basis of in vitro studies. Indeed, many articles about
      this topic have been published these last few years and it has now been
      demonstrated that these new instruments show many advantages compared with
      classical manual instruments. However, they cannot solve every clinical situation
      and the use of manual stainless steel instruments still remains essential.

PMID- 16082878
TI  - [Critical analysis of leakage studies in endodontics].
AB  - Incomplete filling of the root canal is one of the major causes of endodontic
      failure. Endodontic filling techniques and materials which perfectly seal the
      canal are essential for the success of endodontic treatment. Different in vitro
      tests are being used to test the sealing efficiency of endodontic filling
      techniques and materials. A large amount of these tests are leakage tests which
      measure the penetration of a tracer along the root canal filling. Tracers mainly
      are dyes, radio-isotopes, bacteria, bacterial metabolites, fungi and others.
      Apart from the tracer penetration techniques there are also other techniques. The
      electrochemical technique measures electrical current passing through the void
      along the root canal filling. The fluid transport method evaluates through-and
      through voids along the canal filling. With this technique pressure on the water
      at the coronal side of the root canal filling is increased. In case of leakage,
      this will be registered based on the movement of an air bubble in a capillary
      attached to the end of the root. All of the described methods have their
      limitations. The largest limitations are the low reproducibility of some of the
      methods and the absence of standardization. Capillary flow porometry, a method
      well-known from the industry, has recently been applied in dentistry. With this
      method through pores can be evaluated in a standardised and reproducible way.
      Voids which do not extend along the entire root canal filling still have to be
      evaluated with other methods. Despite of the shortcomings of the in vitro leakage
      tests, they remain useful as an initial screening of new materials and techniques
      for canal obturation.

PMID- 16082879
TI  - [The rubber dam in dental practice: use and practical advice].
AB  - Use of rubber dam offers many advantages in endodontic, operative and prosthetic
      procedures. Rubber dam protects the patient against ingestion or inhalation of
      instruments or chemical products, the cavity against contamination and the dental
      practitioner against infections. This article gives technical advice for the easy
      application of rubber dam.

PMID- 16082880
TI  - [LASER applications in endodontics].
AB  - Since the development of the ruby laser by Maiman in 1960 and the application of
      the laser for endodontics by Weichman in 1971, a variety of lasers with a wide
      range of characteristics are now being used in endodontic therapy. In the past
      two decades much experience and knowledge has been gained The first purpose of
      the present paper is to provide an understanding of the essential physical
      science behind laser technology and information on the effects of laser beams on
      tissue (tissue interaction). A second purpose is to summarize laser applications
      in endodontics, including their use in pulp diagnosis, dentinal hypersensitivity,
      pulp capping and pulpotomy, modification of the root canal walls, sterilization
      of the root canal system, cleaning--shaping--obturation of the root canal, and
      endodontic surgery. It will be clear that a number of endodontic procedures with
      conventional treatments cannot provide comparable results or are less effective.

PMID- 16082881
TI  - [The first and second levels of care in endodontics].
AB  - Review of the literature shows a rather low success rate in root canal treatment.
      To make a correct diagnosis, to make a correct estimation of the difficulty, to
      work following 'standard of care' does not always simplify a root canal
      treatment. Referral to an endodontologist, a dentist with a specific competence
      and skills in endodontology, can be a solution. However, to establish a strict
      'referral protocol' is not obvious. Good communication between first and second
      line is important to optimize the service to the patient.

PMID- 16082883
TI  - [Comparison of cytological and histological analysis of gastric mucosa biopsy in
      diagnosing malignant diseases].
AB  - The aim of this study was to determine the value of cytological analysis of an
      imprint of gastric mucosa biopsy compared to the histological evaluation, in
      diagnosing malignant diseases of gastric mucosa. In this study 70 patients, with
      changes of gastric mucosa endoscopically suspect of malignancy were included.
      Biopsy and imprint of gastric mucosa were performed in order to obtain
      morphological diagnosis. In the investigated group 46 patients (65.7%) were male,
      24 patients (34.2%) were female, mean age 60 years (36-83). In 34 patients
      endoscopy finding suggested malignancy, in 23 endoscopy finding was described as
      gastric ulcer, in three as duodenal ulcer, in five as polyp, and in five as
      gastritis. In 42 patients malignancy was proved by pathohistological examination
      while in imprint smears of gastric mucosa biopsy the diagnosis of malignancy was
      made in 46 patients. In five patients malignant cells were found on cytological
      examination of imprint smears, and pathohistological examination did not find
      malignant tumour. In one patient malignant tumour was found on pathohistological
      examination, and cytological examination of an imprint smear did not find
      malignant cells. The results indicate that cytological examination of an imprint
      smear of gastric mucosa biopsy is satisfactory for proving malignant changes. In
      case of positive cytological and negative pathohistological analysis, it is
      recommended to repeat biopsy and imprint cytology in order to obtain
      morphological diagnosis.

PMID- 16082884
TI  - [The presence of CD30 on lymphocytes in the inflammatory infiltrate of acute
      atopic dermatitis].
AB  - Atopic dermatitis (AD) has cellular immunohistochemical features similar to those
      of allergic contact dermatitis (ACD). There is plenty of evidence for T-cell
      activation in this disease such us the presence of T-lymphocytes which carry
      CD30, CD3, CD4, CD45RO markers. The aim of this study was to show the presence of
      lymphocyte-surface antigens including CD30, CD3, CD4, CD45RO in patients with
      acute AD and to compare the presence of the same molecules in patients with acute
      ACD (nickel-induced) because of the possible morphologic difference of these two
      entities. The presence of the stated molecules is immunohistochemically evaluated
      in biopsies of lesional skin in dermis and epidermis. Biopsies were obtained from
      twelve patients suffering from acute AD and from thirteen patients with ACD. The
      results show statistically significant higher average of presence and also much
      higher range of presence of CD30+, CD3+, CD4+, CD45RO+ lympohocytes in dermis and
      epidermis of patients with AD compared to the average and range in patients with
      ACD. Statistically much higher average of CD30, CD3, CD4, CD45RO is noticed in
      those occasions more in dermis than in epidermis in both groups of patients. High
      number of CD30+ lymphocytes in patients with acute AD does not however correlate
      with the severity of the disease evaluated according to clinical score for the
      evaluation of the severity of the disease, so called the SCORAD-index (Severity
      Scoring of Atopic Dermatitis). Our results showed an association betwen CD30
      expression and acute AD but not with acute ACD which could evaluate CD3 as the
      useful marker in differentiating these two diseases.

PMID- 16082885
TI  - [Out-of-hospital use of transcutaneous cardiac pacing].
AB  - Transcutaneous cardiac pacing is a non-invasive method for the treatment of
      serious bradycardias and asystolic cardiac arrest. Due to its simplicity this
      method does not require a long-lasting education. It can be quickly applied
      avoiding all the risks connected with the central venous cannulation. Taking into
      consideration the above mentioned advantages, transcutaneous cardiac pacing has
      become a well-known method of choice for an emergency temporary cardiac pacing.
      This refers especially to the use of transcutaneous cardiac pacing in out-of
      hospital medical centers. This work shows two cases of successful cardiac pacing
      in the patients with life threatening bradycardias under the conditions of
      medicine on the island. The conclusion is that the equipment for transcutaneous
      cardiac pacing should become a part of the standard resuscitation equipment in
      all our centers that are involved in the activities of emergency medicine.

PMID- 16082886
TI  - [Diagnostic evaluation of military recruit who was accidentally found positive on
      hepatitis C virus test: case report].
AB  - The paper reviews diagnostic evaluation of a military recruit who was
      accidentally found positive on hepatitis C virus test during blood donation
      drive. Because of its high tendency of transferring to a chronic disease, acute
      hepatitis C is one of the major problems in public health. Since in a number of
      cases chronic hepatitis C may lead to cirrhosis of the liver and hepatocellular
      carcinoma, it is clear that early identification of the infection and early
      treatment in young people, as military recruits are, is essential. Diagnostic and
      therapeutic evaluation of the military recruit positive on hepatitis C virus test
      must be conducted with maximum thoughtfulness and dedication. It is obligatory to
      inform and include in the treatment recruit himself and more specialists of
      various branches of medicine. Inclusion of a military psychologist and commanding
      officer in evaluation and treatment is desirable. Popular health education and
      preventive medicine measures must be taken by troop physician in such case.

PMID- 16082887
TI  - [Laparoscopic repair of a cholecystoduodenal fistula--a case report].
AB  - Although cholecystoduodenal fistula is traditionally considered a
      contraindication for laparoscopic cholecystectomy, literature search reveals
      reports of cholecystoduodenal fistulae successfully repaired laparoscopically,
      regardless whether cholecystoduodenal fistula was diagnosed before or during
      operation. Here we present a case of preoperatively diagnosed and confirmed
      cholecystoduodenal fistula that was successfully repaired during elective
      laparoscopic cholecystectomy using an Endo-GIA 35 stapling device. Thus we side
      with the growing number of surgeons who do not consider cholecystoduodenal
      fistula to be a contraindication for laparoscopic cholecystectomy.

PMID- 16082888
TI  - [Rituximab in the treatment of indolent non-Hodgkin's lymphoma].
AB  - Indolent Non-Hodgkin's lymphomas (NHL) are a group of slowly progressive immune
      system malignancies that cannot be cured with conventional treatment. Rituximab
      is an anti-CD20 monoclonal antibody that has recently become a part of the
      standard treatment of B-cell lymphoid malignancies. Here we present our
      experience in 25 patients with indolent NHL treated with rituximab with or
      without chemotherapy. Rituximab was administered at 3-4 week intervals in the
      standard dose of 375 mg/m2. 88% of the patients responded, 16 achieved a complete
      and 6 partial remission. Estimated 2-year actuarial survival is 63%. Response and
      survival rates were significantly better in patients with favorable prognosis
      (lower IPI score). Adverse effects related to rituximab occurred in 2 patients
      and were mild. Our results are completely comparable to previously reported
      studies and show that rituximab is effective and safe for the treatment of
      indolent B-cell NHL.

PMID- 16082889
TI  - [Balint group--aid to general practitioner].
AB  - Professional education of general practitioner is mainly focused on biomedical
      aspects of treating somatic diseases, while psychological components of somatic
      diseases, as well as doctor-patient relationship, are generally neglected.
      General practitioner is in healing process daily exposed to considerable
      frustrations in relationships with patients. Some frustrations stem from
      unrecognized and neglected psychological and emotional aspects of somatic
      diseases which manifest in the doctor-patient relationship. The aim of this work
      is to show that Balint group can enhance general practitioner's professional
      capability, as well as his professional satisfaction, teaching him how to
      recognize psychological needs and problems which are integral part of somatic
      diseases and doctor-patient relationship as well.

PMID- 16082890
TI  - [Beta-lactamases in laboratory and their role in resistance Part I.: Evolution of
      bacterial resistance mediated by beta-lactamases].
AB  - Beta-lactamases are the commonest cause of bacterial resistance to beta-lactam
      antibiotics. They have been classified phenotypically by their isoelectric point,
      substrate profile, susceptibility to inhibitors and genetic origin. Chromosomal
      beta-lactamases are typical for certain bacterial species and plasmid beta
      lactamases are transferable between different species and genera. Sequencing of
      beta-lactamase genes enabled to divide them into four classes: A, B, C and D. The
      ability of a beta-lactamase to confer resistance depends on its location,
      kinetics, quantity and physicochemical conditions. First beta-lactamases were
      described soon after introduction of penicillin. Plasmid-mediated broad-spectrum
      beta-laktamases appeared in the middle 60-s of the XX century and confer
      resistance to penicillins and some first generation cephalosporins. They include
      TEM-1, TEM-2, SHV-1, ROB, BRO, OXA and PSE beta-lactamases and are transferred by
      conjugation between different species and strains of Gram-negative bacteria. The
      new beta-lactam agents nowadays are compromised mostly by extended-spectrum beta
      lactamases, inhibitor-resistant beta-lactamases and carbapenemases. Extended
      spectrum beta-lactamases (ESBLs) were described for the first time 20 years ago
      and are derived from the parental TEM and SHV-1 beta-lactamases by mutations that
      alter the configuration of the active site to expand their spectrum of activity.
      They hydrolyse oxymino-cephalosporins and aztreonam. The rapid and accurate
      laboratory detection of ESBLs is important for choosing appropriate antibiotic
      therapy. Infections caused by Enterobacteriaceae producing ESBLs pose a
      therapeutic problem due to multiple antibiotic resistance which includes non-beta
      lactam antibiotics as well. Carbapenems are the first-line antibiotics for
      treatment of such infections.

PMID- 16082891
TI  - [Environmental tobacco smoke and children: assessment of exposure and health
      effects].
AB  - AIMS: To assess prospectively 1) concentrations of metals and progesterone in
      placental tissue related to cigarette smoking; 2) the effect of parental smoking
      on the susceptibility to colds in preadolescent children during winter months.
      METHODS: The first study comprised healthy parturients with median age 28 years,
      29 non-smokers and 27 women who smoked during pregnancy and/or within one year
      before last pregnancy. Placentas were collected after delivery at term and metals
      (by atomic absorption spectrometry) and placental progesterone (by specific
      radioimmunoassay) were analysed. A comparative study in 337 school children,
      second graders, was undertaken in central urban and suburban area. Information on
      children and families and on parental smoking was collected. During the six-month
      period incidence of acute respiratory diseases was followed-up. RESULTS: In
      placentas of smoking vs. non-smoking women a twofold increase in cadmium
      concentration, a decrease in iron and a half of progesterone concentration as a
      biomarker of effect of tobacco smoke exposure were found. Nearly 59 percent of
      Croatian children live in the household with at least one smoker. The incidence
      of colds in children was 25%. The study demonstrates an exposure-response
      relationship between the parental smoking and the reporting rates for doctor
      diagnosed upper respiratory illness; in children exposed to both parents' smoke
      odds ratio was 2.03 and in children from the family with one smoker odds ratio
      was 1.65. CONCLUSIONS: Results support the established association of tobacco
      smoke exposure with increased placental cadmium concentration, and concomitant
      reduction of placental progesterone is a new evidence on health risk for mother
      and foetus. The higher risk of frequent colds in children related to
      environmental tobacco smoke is a relevant public health problem.

PMID- 16082893
TI  - [Lead poisoning by contaminated flour: an unfinished story].
AB  - A young Arab woman was diagnosed with severe lead poisoning in the early 80's.
      Detailed epidemiologic studies revealed many additional cases of lead poisoning
      in the rural population south of Nablus and a population survey conducted among
      schoolchildren revealed increased blood lead levels in 30% of the children. The
      source of poisoning was contamination from home-made flour by lead fillings used
      to secure the housing of the driveshaft to the millstone. Of the 146 village
      mills surveyed, lead concentrations in freshly ground flour exceeding 1.5 ppm
      were found in 8% of the mills. Following our original report, identical outbreaks
      caused by contaminated flour were reported from Spain, Turkey, Greece and
      Albania. In spite of administrative efforts to prevent the use of lead in flour
      mills, the problem still persists. In Israel itself, similar subsequent outbreaks
      have been documented in the Upper Galilee, and recently in the Hebron district.
      Apparently, the problem has existed since antiquity because flour mills employing
      lead parts were introduced to this and other countries during the Roman conquest.
      A coordinated international effort is essential to eliminate this unique and
      serious health threat from the environment.

PMID- 16082894
TI  - [Control of life-threatening hemorrhage from the neck and groin by a Foley
      catheter in cases of penetrating trauma].
AB  - This article describes the use of a Foley catheter placed through the entrance of
      the penetrating wound to control hemorrhage from sites that are difficult to
      access by direct pressure, such as neck and groin. A case describing the use of
      the method is presented. This technique is almost unknown in Israel even though
      it has been published in the medical literature. Everyone involved in treating
      trauma patients should know this method for use in appropriate situations.

PMID- 16082895
TI  - [Subacromial hematoma due to rotator cuff rupture].
AB  - This is an unusual case report of an elderly patient with spontaneous acute
      rupture of rotator cuff complicated by large subacromial hematoma. The hematoma
      fluid was aspirated with significant reduction of pain. The shoulder movements
      were restored after one month with conservative therapy. The compensatory role of
      preserved deltoid muscle is considered in the rehabilitation of normal shoulder
      movement, which may replace aggressive immobilization or surgical procedures in
      the elderly population. Investigation of hematoma fluid compared with blood 24
      hours after the event revealed severe lactic acidosis with low glucose level,
      preserved red blood cell count and significant decrease of white blood cells.
      There were normal values of CBC, pH, lactate and glucose in blood. These results
      showed high susceptibility of leukocytes to anaerobic and acid environment and
      its dependence on oxygen supplement.

PMID- 16082896
TI  - [Lack of treatment continuance: an obstacle for controlling blood pressure].
AB  - INTRODUCTION: Blood pressure is one of the most prevalent risk factors for CVD.
      Despite the large arsenal of medications, the rate of BP control is not optimal.
      We studied the amount of attention family physicians pay to BP readings and
      treatment recommendations of hypertensive patients that were discharged from the
      hospital. METHODS: We included 98 consecutive hypertensive patients (mean age
      68.5 +/- 1.1, 44% males) admitted to the hospital. Excluded were patients
      referred to the hospital from a nursing home. BP measurements were obtained at
      ER, admission to the ward, 2nd day of admission and day of discharge. Recommended
      treatment was obtained from the discharge letter. A phone call was made to each
      patient, 4-8 weeks after discharge, and data was obtained regarding recent BP
      levels and the current treatment. RESULTS: BP control was achieved in 48% of the
      patients at hospital discharge and 47% at follow-up. Among patients that received
      different treatment at follow-up because of the physician's advice or because
      they were considered to have a high BP (24 patients), BP control was reduced from
      63% at discharge to 50% at follow-up. This reduction was attributed to decreased
      dosage of medications and to the replacement of medications with drugs from the
      same group, but given at nonequivalent doses. Ten patients that were controlled
      at discharge but not at follow-up were given fewer medications than recommended
      (2.7 vs. 3.2). Among the noncontrolled patients with BP > 140/90 at follow-up,
      treatment was not changed for 48%. CONCLUSION: The blood pressure treatment
      guidelines are not implemented, and the data regarding BP control that appears in
      the discharge letter is not adequately used by the family physicians. A better
      relationship between hospitals and family practice should be obtained to aid in
      controlling BP.

PMID- 16082897
TI  - [Streptococcus group C bacteremia and meningitis].
AB  - Group C streptococci are common causative agents of infections in animals, but a
      rare cause of bacteremia and meningitis in humans. Severe infections caused by
      this bacterium are associated with high morbidity and mortality rates. This
      article presents a case study of a young patient who suffered from bacteremia and
      meningitis that were caused by streptococcus group C. The clinical
      manifestations, prognosis and treatment options of this kind of infection are
      discussed.

PMID- 16082898
TI  - [Knowledge management in health organizations].
AB  - BACKGROUND: In 2002 the head of the Israel Defense Forces (IDF) Technology and
      Logistics Command took a strategic decision to manage knowledge across the
      organization. The IDF Medical Corps was one of the initiation sites selected.
      Insights from the process of establishment of a knowledge management (KM) system
      in the IDF Medical Corps as a health organization (HO) are described. METHODS:
      IDF's medical services were identified, mapped and their participants
      interviewed, as were KM personnel in Israeli HOs. Information analysis pointed to
      the medical rendezvous (MR) as the central process for initiation of KM. The
      knowledge challenges were identified, and knowledge services and administrative
      interventions were planned. RESULTS INCLUDING KM CHALLENGES AND RESPONSE: The MR
      was found to be the process in which most of the clinically and administratively
      significant decisions in HO's were taken. Practitioners had large clinical and
      administrative knowledge gaps. Medical and administrative knowledge originated
      from various sources, in many formats. It could not be retrieved either easily or
      completely, was usually presented in an inconvenient form for assimilation, and
      was not always updated. Therefore, the MR was selected as the initial
      intervention point. Optimally, a comprehensive solution providing access to high
      quality knowledge can be a knowledge portal, including diagnostic indexing as a
      key for retrieval of information. Furthermore, indexed clinical, administrative,
      services list, quality assurance, risk management, and continuing medical
      education knowledge services, as well as a collegial and administrative feedback,
      link all entities involved into a knowledge community. This may increase the
      opportunity for optimal and efficient managed care.

PMID- 16082899
TI  - [Low back pain--an additional aspect].

PMID- 16082900
TI  - [Treatment approach to localized esophageal cancer--what have we learned so
      far?].
AB  - The treatment of localized esophageal cancer (LEC) is under extensive debate.
      Treatment approaches include surgery or radiation alone, surgery with
      preoperative or postoperative radiation, preoperative or postoperative
      chemotherapy and definitive or preoperative chemoradiation. In fact, the type of
      therapy patients receive is often dependent on the actual medical field of the
      treating physician (surgery, oncology, etc.). The use of multiple treatment
      approaches toward LEC primarily reflects the scarcity of data that is derived
      from controlled randomized trials and the poor results of current therapies. In
      spite of the above, the cumulative data suggest that surgery and chemoradiation
      are the two treatment options in LEC and that their combined approach, i.e.
      preoperative chemoradiation, has not been proven to have a survival advantage
      over each one of these methods, and should therefore still be considered
      investigational. This article will review the available data on the various
      treatment approaches that are being used against LEC.

PMID- 16082901
TI  - [May children and adolescents with a solitary kidney participate in sports
      activities?].
AB  - The presence of a solitary kidney in children and adolescents is not a rare
      condition, and flank injury in this context may result in renal impairment, with
      subsequent nephrectomy, dialysis or kidney transplantation. Participation in
      sports activities commonly results in pediatric injuries, and the kidneys are the
      most frequently affected organs during blunt abdominal trauma. Nonetheless, the
      incidence of major renal trauma during sports activities, according to pediatric
      trauma registries in the United States, is still relatively low. Subsequently,
      there is an ongoing debate in the literature regarding the safety of
      participation of children with a solitary kidney in sports activities. The
      literature review presented reveals that the general recommendation has shifted
      from a formerly restrictive attitude towards a more permissive one, based upon
      pooled data and calculated risks.

PMID- 16082902
TI  - [Occupational aspects of low back pain].
AB  - Low back pain is a very common ailment among workers of all ages. Approximately
      60-90% of the adult population suffers from low back pain at least once during
      their life time. The yearly incident rate of low back pain is about 1-2%. This is
      one of the major causes of occupational illnesses and absence from work. A high
      rate of low back pain is found among workers involved with heavy physical labour
      and also among truck drivers. Risk factors for low back pain are intense heavy
      labour, lifting heavy objects, protracted static positions, repetitive movements
      and awkward body postures accompanied by vibration. Prolonged standing and
      sitting are not risk factors for low back pain. Work dissatisfaction, low wages
      and low levels of education are possible predictors for low back pain. The only
      reliable predictor of future low back pain is the evidence of previous back pain
      as disclosed during the preemployment health examination.

PMID- 16082903
TI  - [Blocking of the thyroid against I-131 following a nuclear disaster].
AB  - The Chernobyl accident, the recent terrorists' attacks and constant threats, have
      all once again evoked the fear of a nuclear disaster, in Israel and worldwide.
      Iodine-131 is a major fission product of nuclear reactors and is highly likely to
      be released into the atmosphere in severe nuclear disasters. The radioiodine is
      released as a gas, easily spreads over large areas and is easily absorbed via the
      respiratory system. Iodine-131 emits gamma and beta radiation in high energies,
      and is readily absorbed by the thyroid which is a target organ for iodine. The
      resulting exposure to the thyroid might be very high. A sharp increase in thyroid
      cancer incidence in children was observed following the Chernobyl accident. This
      article reviews the medical knowledge about strategies and medications aimed at
      minimizing the absorption of radioiodine into the thyroid. In addition to regular
      safety means such as sheltering, restriction of locally produced food products
      and relocation of the population, the best prophylaxis against thyroid exposure
      is overloading the gland with stable iodine (as potassium iodide), as soon as
      possible. Recently, the Israeli government decided to distribute Potassium Iodide
      tablets to the population in the vicinity of the two nuclear research centers in
      the country. When this treatment is contraindicated, iodine free thionamides or
      potassium perchlorate are suggested.

PMID- 16082904
TI  - [Post partum anal incontinence].
AB  - Vaginal delivery is one of the main causes of anal incontinence. While previously
      postpartum anal incontinence was attributed to neurological damage to the pelvic
      floor and the rectal sphincter, today we know that mechanical injury plays an
      important role, especially when symptoms start soon after delivery. Risk factors
      for postpartum fecal incontinence are: forceps delivery, nulliparity, birth
      weight over 4 kilograms and persistent occiput posterior presentation of the
      fetal head. Anal incontinence developed in 42% of women who had posterolateral
      episiotomy. Therefore, the main focus of the treating physician should be on
      prevention by avoiding birth trauma followed by early recognition and skilful
      correction.

PMID- 16082905
TI  - [Guidelines for the prevention and treatment of atherosclerosis and
      cardiovasculer diseases: general recommendations--hypertension].
AB  - Atherosclerosis is one of the principal causes of morbidity and mortality
      worldwide. The recent decades have witnessed great advances both in the
      identification of risk factors for the development of atherosclerosis and the
      treatment of its complications. This effort was rewarded with the reduction of
      mortality rates from cardiovascular diseases. The need for an update of the
      recommendations for the prevention of atherosclerosis and cardiovascular diseases
      stems from a large body of recently published trials, leading to fundamental
      changes in the way we treat patients with various levels of risk. The first part
      of the guidelines deals with general recommendations, applicable to the
      population as a whole, at all levels of risk, together with recommendations for
      the treatment of hypertension.

PMID- 16082906
TI  - Overprotection phenomenon with dying dementia patients.

PMID- 16082907
TI  - Whose life is it, anyway? The federal government vs. the state of Oregon on the
      legality of physician-assisted suicide.

PMID- 16082908
TI  - Medicare benefit still not accurately defined.

PMID- 16082909
TI  - When palliative medicine is palliative care.

PMID- 16082910
TI  - Benefits of massage therapy should not be overlooked.

PMID- 16082911
TI  - The needs of children with life-limiting conditions: a healthcare-provider-based
      model.
AB  - Pediatric hospice and palliative care has progressed in recent years with the
      development of new programs and models of care. Missing from the empirical
      literature, however is a model of the needs of children. The purpose of the
      present study was to develop an empirically based conceptual model of the needs
      of children with life-limiting conditions. Recognizing the value of both
      qualitative and quantitative data, concept mapping methodology was selected as an
      effective way to obtain data that reflected both the "big picture" and subtleties
      of pediatric end-of-life needs. The seven-cluster concept map appeared best in
      terms of both interpretability and parsimony. This model includes the following
      clusters of needs: 1) pain, 2) decision making, 3) medical system access and
      quality, 4) dignity and respect, 5) family-oriented care, 6) spirituality, and 7)
      psychosocial issues. We believe that the development of a comprehensive model of
      the needs of such children is a step toward concrete, measurable, and effective
      support for children and their families.

PMID- 16082912
TI  - Predictors of social service staff involvement in selected palliative care tasks
      in nursing homes: an exploratory model.
AB  - Little research has been conducted on nursing home social service staff and end
      of-life care in nursing homes. To address this gap, a cross-sectional study on
      end-of-life issues for people with dementia in nursing homes was conducted in New
      York State, in which 138 nursing home social service staff participated. This
      exploratory study examined issues such as perceived confidence, perceived
      influence, and demographic variables in relation to self-reported frequency of
      tasks related to palliative care of nursing home residents with dementia. Results
      showed that participants in this survey who discussed specific treatment issues
      during advance directive discussions perceived themselves to have higher degrees
      of influence in their respective facilities, were directors or managers of their
      departments, and were more likely to engage in tasks related to palliative care.

PMID- 16082913
TI  - Terminal restlessness as perceived by hospice professionals.
AB  - Any hospice professional can identify the syndrome known as terminal
      restlessness, and all would agree that it is extremely distressing to patients as
      well as their families and caregivers. Often, caregivers cannot ameliorate the
      anguish many patients experience at life's end. Many clinicians assert that the
      causes are physical resulting from medication toxicity, organ shutdown and the
      associated metabolic changes, pain, urinary or fecal retention, dyspnea and
      related hypoxia, and sepsis. Yet, many also credit psychosocial and spiritual
      distress as precipitating factors. The purposes of this study were twofold: to
      compare the perceptions of practicing hospice clinicians with the literature
      related to terminal restlessness, and to determine if their experience with
      terminal restlessness agreed with the components of the one established scale for
      terminal restlessness found in the literature. In general, the study findings
      corresponded to the literature in regards to frequency, definition, causes, and
      behavioral manifestations of terminal restlessness. The clinicians in the study
      supported the impact of psychosocial and spiritual causes of terminal
      restlessness and defined the phenomenon in terms of time period; emotional,
      physical, and spiritual distress; changes in consciousness; and increased
      activity. However, the study did not support the inclusion of impaired
      consciousness and withdrawal as comprised in the terminal restlessness scale.

PMID- 16082914
TI  - Anticipatory grief and psychological adjustment to grieving in middle-aged
      children.
AB  - This study examines the effect of anticipatory grief on personal adjustment in
      middle-aged adult children following the death of their last surviving elderly
      parent. Data were analyzed from a study of adult children's perspectives of an
      elderly parent's death conducted by the Philadelphia Geriatric Center,
      Philadelphia, Pennsylvania. The results of this study indicate that adult
      children who experienced anticipatory grief were likely to report feeling better
      adjusted to the death of their elderly parent, yet the composite measure used to
      assess degree of personal adjustment indicates a negative relationship between
      the anticipation of death and personal adjustment following the actual loss. This
      finding was consistent across gender and racial and ethnic distinctions among
      adult children who participated in this study. The significance of this finding
      for grief work and its implications for future research are discussed.

PMID- 16082915
TI  - Humor in hospice care: who, where, and how much?
AB  - Humor has been identified as an intrinsic social phenomenon occurring in all
      groups throughout human history. It is among the most prevalent forms of human
      social behavior yet one of the least understood or defined. Although researchers
      in a number of disciplines have studied the effects of humor on patients, limited
      work has focused on end-of-life care. The present study investigated social
      interactions involving humor in hospice settings using nonparticipant
      observation. Results revealed that humor was present in 85 percent of 132
      observed nurse-based hospice visits. Of these, hospice patients initiated humor
      70 percent of the time. These findings were consistent regardless of hospice
      setting. Humor was spontaneous and frequent, and instances of humorous
      interactions were a prevalent part of everyday hospice work.

PMID- 16082916
TI  - Hyperalgesia and opioid switching.
AB  - Opioids, intended to abolish pain, can unexpectedly produce hyperalgesia,
      particularly during rapid opioid escalation. Opioid switching could be a
      therapeutic option in a condition of opioid-induced tolerance or hyperalgesia,
      but conversion ratios between opioids are difficult to apply in this context and
      require strict surveillance and expertise. This situation is challenging, because
      the rapid escalation of opioid doses, possibly due to the development of opioid
      induced tolerance, can cause hyperalgesia. To avoid this adverse effect,
      clinicians need to refine their assessment of pain treatment and consider opioid
      switching. The authors present a case report in which switching from fentanyl to
      methadone was effective in a patient who developed hyperalgesia as a consequence
      of a rapid opioid escalation. Regardless of the expected clinical improvement of
      opioid switching using lower doses of the second opioid, the final dose of the
      second opioid was exaggeratedly low, probably as a consequence of the
      disappearance of hyperalgesia induced by the first opioid. The results of this
      case and others like it may help practitioners develop a meaningful approach
      during opioid escalation, possibly anticipating the need for opioid switching or
      other alternative measures for patients with uncontrolled cancer pain.

PMID- 16082917
TI  - The therapeutic application of melatonin in supportive care and palliative
      medicine.
AB  - Melatonin is a hormone produced mainly in the pineal gland. Plasma levels exhibit
      a circadian variation with the highest concentration occurring at night. The
      human biologic effects of melatonin depend upon the time of day it is made
      available. One of these effects is the setting and resetting of circadian clocks
      (chronobiotic effect). Additionally, it may be a potent antioxidant and
      immunomodulator and has been shown to have antitumor, anticytokine, anti
      insomnia, and anticachexia effects. Melatonin has also been shown to improve
      survival and performance status in patients with advanced cancer. Objective tumor
      response occurs with melatonin alone or when combined with interleukin-2 (IL-2).
      Further, melatonin reduces radiation- and chemotherapeutic-induced toxicity.
      Symptomatic and circadian disruption is linked to increased cancer risk. The
      chronobiotic capacity of melatonin to reset circadian clocks may provide a
      verifiable strategy to reduce cancer risk and enhance quality of life by
      diminishing cancer-induced circadian disruption.

PMID- 16082918
TI  - Case study--Living wills vs. the will of loved ones.

PMID- 16082919
TI  - Influence of selected fruit tree pollen on life history of Euseius stipulatus
      (Acari: Phytoseiidae).
AB  - Euseius stipulatus (Athias-Henriot) is a predatory mite widespread in the
      Mediterranean region considered to be important for the biological control of
      spider mites in citrus orchards. Development, survival and reproduction of this
      phytoseiid mite feeding on seven commercially obtained pollen were studied under
      constant laboratory conditions (20 +/- 1 degrees C, RH 65 +/- 5%, photoperiod
      16L: 8D h). Mites were kept individually at rearing units with ample quantity of
      almond (Prunus amygdalus Batch), apple (Malus domestica Borkh), apricot (Prunus
      armeniaca L.), cherry (Prunus avium L.), pear (Pyrus communis L.), plum (Prunus
      domestica L.) and walnut (Juglans regia L.) pollen as food source. Developmental
      time from egg to adult varied between the several pollen tested from 8.38 +/-0.08
      to 9.58 +/- 0.11 days for females and from 8.23 +/-0.12 and 9.07 +/-0.12 days for
      males. Female longevity varied from 11.53 +/- 1.22 to 51.38 +/- 2.45 days, while
      fecundity ranged from 22.84 +/- 2.30 to 43.61 +/- 3.78 eggs/female. The predator
      was unable to reproduce when feeding on walnut pollen. Data were submitted to
      life table analysis and values of the intrinsic rate of increase were derived,
      ranging from 0.079 to 0.146 (day(-1)). The cumulative Weibull function that was
      used to describe the age specific survival of females produced excellent fits to
      the survival data. Results show that almond, plum, cherry and apricot pollen
      possess higher nutritional value for E. stipulatus than pear and apple pollen and
      thus may contribute in sustaining and increasing the predator population in field
      conditions. Walnut pollen can be utilized by the predator only to survive during
      short periods of time when principal or alternative food sources are scarce.

PMID- 16082920
TI  - Inbreeding depression of female fecundity by genetic factors retained in natural
      populations of a male-haploid social mite (Acari: Tetranychidae).
AB  - We previously determined that certain recessive genes decrease female fecundity
      in a haplo-diploid spider mite, Stigmaeopsis miscanthi (Saito). However, whether
      the depression was caused by the breakdown of heterosis or the expression of
      deleterious genes retained in a population could not be determined, because we
      had started our inbreeding experiment from a mixture of two isolated populations.
      In order to answer this basic question, inbreeding effects on survival and
      fecundity were measured for eight small populations occurring far from the two
      initial populations. There was little depression of immature survival of inbred
      lineages in all populations. On the other hand, in two inbred lineages, both
      originating from the smallest populations, female oviposition decreased
      significantly with the increase of Wrights f-value, showing that mildly
      deleterious genes are actually retained even in natural populations of haplo
      diploid organisms.

PMID- 16082921
TI  - Significance of habitat type for the genetic population structure of Panonychus
      citri (Acari: Tetranychidae).
AB  - Restricted migration and habitat fragmentation promote genetic differentiation
      between populations. Because most of the hosts of Panonychus citri are woody
      plants, mainly citrus trees that are usually planted at intervals of several
      metres, this mite likely faces more risks (e.g., starvation) by dispersing
      between host plants, compared to other spider mite species that infest both
      herbaceous and woody plants, such as Tetranychus urticae. Such a limited gene
      flow between patches (host plants) can lead to differentiation of populations
      even within a small area. Therefore, we hypothesize that P. citri populations are
      genetically differentiated not only between distant populations but also within
      small areas, such as within a grove. To test this hypothesis, we investigated the
      divergence of P. citri populations in Japanese citrus groves according to a
      hierarchical arrangement of geographical distance, ranging from distant
      populations (10 groves distributed throughout different areas in two major
      Japanese islands; this level of analysis is referred to as 'geographic') to local
      populations (different trees in a specific grove; 'local'). Three molecular
      markers were used: an esterase locus, one microsatellite and a point mutation in
      the mitochondrial cytochrome oxidase subunit I. At a local level acaricide
      susceptibility tests were also performed using two acaricides: fenpyroximate (25
      ppm) and etoxazole (3.33 ppm). At a broad geographic level the gene diversity
      decreased with decreasing area size and distance between populations. By
      contrast, at the local level, populations maintained a significant level of
      variation between trees within groves, and the divergence within groves was
      higher than between groves. Whereas no statistical difference of the mortalities
      was detected among groves for the two acaricides tested, the difference was
      statistically significant among trees within groves in fenpyroximate (ANOVA,
      p<0.025) and marginal in etoxazole (0.1<p<0.05). We concluded that P. citri
      populations maintain a higher level of variation between trees (or patches of
      trees) within groves than between groves at the local level, though the gene
      diversity tended to be smaller with decreasing distance between populations at
      the geographical level. Results are discussed in relation to the dispersal
      behaviour of spider mites.

PMID- 16082922
TI  - Pathogenicity of Beauveria bassiana and Metarhizium anisopliae to the tobacco
      spider mite Tetranychus evansi.
AB  - Seventeen isolates of Metarhizium anisopliae (Metschnikoff) Sorokin and two
      isolates of Beauveria bassiana (Balsamo) Vuillemin were evaluated for their
      pathogenicity against the tobacco spider mite, Tetranychus evansi Baker &
      Pritchard. In the laboratory all the fungal isolates were pathogenic to the adult
      female mites, causing mortality between 22.1 and 82.6%. Isolates causing more
      than 70% mortality were subjected to dose-response mortality bioassays. The
      lethal concentration causing 50% mortality (LC5o) values ranged between 0.7 x
      10(7) and 2.5 x 10(7) conidia ml(-1). The lethal time to 50% mortality (LT50)
      values of the most active isolates of B. bassiana and M. anisopliae strains
      varied between 4.6 and 5.8 days. Potted tomato plants were artificially infested
      with T. evansi and treated with B. bassiana isolate GPK and M. anisopliae isolate
      ICIPE78. Both fungal isolates reduced the population density of mites as compared
      to untreated controls. However, conidia formulated in oil outperformed the ones
      formulated in water. This study demonstrates the prospects of pathogenic fungi
      for the management of T. evansi.

PMID- 16082923
TI  - Baseline susceptibility of persea mite (Acari: Tetranychidae) to abamectin and
      milbemectin in avocado groves in Southern California.
AB  - Persea mite, Oligonychus perseae Tuttle, Baker, and Abatiello, susceptibility to
      abamectin and milbemectin was evaluated in 2003 to determine baseline
      susceptibility levels in avocado groves in San Diego and Ventura Counties
      (California, USA) where more than 70% of the state's avocado production is
      concentrated. Milbemectin has yet to be used in avocado production in California
      and abamectin has been available for use since 1999. Baseline susceptibility
      ratios (in relation to the most susceptible population) of five persea mite field
      strains to milbemectin varied 2.1- to 2.8-fold at the LC50 and LC90,
      respectively. The susceptibility of seven field strains to abamectin varied
      slightly more (2.1- to 3.5-fold) with one strain subjected to seven sprays over
      the past 4 years showing slight but significant separation of LC50 and LC90's
      from the most susceptible strain, which is suggestive of the early stages of
      resistance to this product. Based on these data, baseline susceptibility levels
      are proposed that might be used to monitor for future persea mite resistance to
      these chemicals as their use in California avocado production continues.

PMID- 16082924
TI  - Lethal and sub-lethal selectivity of fenbutatin oxide and sulfur to the predator
      Iphiseiodes zuluagai (Acari: Phytoseiidae) and its prey, Oligonychus ilicis
      (Acari: Tetranychidae), in Brazilian coffee plantations.
AB  - Lethal concentration (LC) has been widely used to estimate pesticide toxicity.
      However, it does not consider the sub-lethal effects. Therefore we included the
      instantaneous rate of increase in association with LC to estimate population
      level effects of the acaricides fenbutatin oxide and sulfur on the predator
      Iphiseiodes zuluagai and its prey, the phytophagous southern red mite,
      Oligonychus ilicis. The predator was 32.84x and 17.20x more tolerant to
      fenbutatin oxide and sulfur, respectively, than its prey, based on LC50 estimates
      obtained from acute concentration-mortality bioassays. The instantaneous rate of
      population growth in both mite species decreased with increasing acaricide
      concentration. Both acaricides provided effective control of O. ilicis at their
      recommended concentrations, but sulfur drastically compromised the predator
      populations quickly leading them to extinction due to the low reproductive
      potential of this species compared with its prey.

PMID- 16082925
TI  - Development and reproduction of Stratiolaelaps scimitus (Acari: Laelapidae) with
      fungus gnat larvae (Diptera: Sciaridae), potworms (Oligochaeta: Enchytraeidae) or
      Sancassania aff. sphaerogaster (Acari: Acaridae) as the sole food source.
AB  - Stratiolaelaps (=Hypoaspis) miles (Berlese) (Acari: Mesostigmata: Laelapidae) is
      a polyphagous soil-dwelling predatory mite that is widely marketed for use in
      greenhouse production systems to manage populations of dark-winged fungus gnats,
      Bradysia spp. (Diptera: Sciaridae) and for supplemental control of thrips. The
      suggestion by Walter and Campbell (2003, Biol. Control 26: 253-269) that North
      American commercial cultures of S. miles may actually be S. scimitus was
      confirmed. The development and reproduction at 21-23 degrees C of S. scimitus
      provided ad libidum with one of three different prey--the fungus gnat Bradysia
      aff. coprophila (Lintner), potworms (Enchytraeidae), or Sancassania aff.
      sphaerogaster (Zachvatkin, 1937) (Acari: Astigmata: Acaridae)--were compared.
      Developmental duration of the egg and non-feeding larval stages were 2.47 and
      1.11 days, respectively; mortalities were 8.3 and 5.5%. Stratiolaelaps scimitus
      failed to develop beyond the protonymphal stage when provided with S. aff.
      sphaerogaster alone, although some feeding was observed. Development and
      reproduction of S. scimitus was successful on both fungus gnat larvae and
      enchytraeids, with no influence of prey on protonymphal duration (4.70 days) and
      mortality (8.3%), or on deutonymphal duration (4.61 days) and mortality (6.1%).
      Adult female S. scimitus feeding on potworms, compared to those feeding on fungus
      gnat larvae, had a significantly shorter pre-oviposition period (2.69 vs. 4.59
      days). However, diet did not influence other adult female developmental or
      reproductive characteristics (oviposition period, 18.6 days; post-oviposition
      period, 6.2 days; total adult longevity, 27.3 days; total number of eggs, 26.5).
      S. scimitus reared on potworms tended (p = 0.06) to have a higher intrinsic rate
      of increase, a higher finite rate of increase and a shorter doubling time (rm =
      0.142 day(-1), lambda = 1.153, Dt = 4.85 days) than those reared on fungus gnat
      larvae (rm = 0.105 day(-1), lambda = 1.110, Dt = 6.58 days), but differences in
      net reproductive rate (R0) and generation time (G) were not significant.

PMID- 16082926
TI  - Larval Cryptothelea gloverii (Lepidoptera: Psychidae), an arthropod predator and
      herbivore on Florida citrus.
AB  - The orange bagworm (OBW), Cryptothelea gloverii (Packard) (Lepidoptera:
      Psychidae) was previously reported feeding on citrus fruit and foliage and
      preying upon the camphor scale Pseudaonidia duplex (Cockerell) (Homoptera:
      Coccidae). In this study using laboratory assays, OBW preyed upon citrus rust
      mite, Phyllocoptruta oleivora (Ashmead) (Acari: Eriophyidae) and consumed eggs
      and adults of both P. oleivora and Panonychus citri (McGregor) (Acari:
      Tetranychidae), two important pest mites on Florida citrus. OBW was also observed
      to feed on the purple scale, Lepidosaphes beckii (Newman) (Homoptera:
      Diaspididae) and on a fungus (Penicillium sp.). OBW fed on orange and grapefruit
      leaves by starting from the border and eating part of the leaf, by chewing holes,
      or consuming the outer epithelium of either the axial or abaxial surface of the
      leaf without penetrating through the leaf. OBW was observed in orange orchards in
      association with fruit extensively russeted by P. oleivora feeding. Laboratory
      assays revealed that OBW larvae preferred to feed on oranges infested with P.
      oleivora rather than on clean fruits that were free of mite feeding damage.
      Feeding damage to citrus fruit by OBW larvae results in one to several holes
      being eaten into the rind or albedo, without damage to the fruit sacs.

PMID- 16082927
TI  - Effect of temperature on reproductive parameters and longevity of Tyrophagus
      putrescentiae (Acari: Acaridae).
AB  - The effect of temperature on reproductive parameters and longevity of the mold
      mite, Tyrophagus putrescentiae (Schrank) was examined at seven constant
      temperatures, ranging from 10 to 34 degrees C, and a relative humidity of 90 +/-
      5%. Preoviposition period and fecundity were adversely affected by extreme
      temperatures and the oviposition period increased as temperature was reduced.
      Different patterns were observed for longevity data for males and females, with
      greater longevities for males at intermediate temperatures and more similar
      values for both sexes at extreme temperatures. Polynomial and non-linear models
      provided a good fit of the relationship of reproductive and longevity parameters
      with temperature. The effect of temperature on the intrinsic rate of increase of
      T. putrescentiae populations was established by the non-linear Lactin model. The
      optimum temperature for development was obtained at 30 degrees C. At this
      temperature, the population doubling time is 1.75 days. The lower and upper
      thresholds for T. putrescentiae populations were established at 10.4 and 34.8
      degrees C, respectively. Altogether, these data provide basic information to
      develop sound physical control strategies of the mold mite.

PMID- 16082928
TI  - S-isorobinal as the female sex pheromone from an alarm pheromone-emitting mite,
      Rhizoglyphus setosus.
AB  - The female sex pheromone of Rhizoglyphus setosus Manson (Astigmata: Acaridae) was
      identified as S-isorobinal (4S-4-isopropenyl-3-oxo-1-cyclohexene-1
      carboxyaldehyde), which stimulated males sexually and enhanced the frequency of
      the male's tapping and mounting behavior. Although the female hexane extract
      indicated no sign of sex pheromone activity against tested males, possibly due to
      the presence of the alarm pheromone neryl formate, an SiO2 column fraction
      containing isorobinal elicited sex pheromone activity at a dose of one female
      equivalent. The stereochemistry of natural isorobinal was identified as S by an
      HPLC using a chiral column. Both S- and R-isorobinals exhibited maximum activity
      at the same dose of 1 and 10 ng with a convex dose-response relationship. Amounts
      of S-isorobinal were determined to be 11.7 +/- 1.0 ng per female and 6.4 +/- 1.3
      ng per male by GLC. This is the second example of two pheromones (the alarm
      pheromone neryl formate, and the sex pheromone S-isorobinal) demonstrated to be
      components of the same opisthonotal gland secretion.

PMID- 16082929
TI  - Impact of ivermectin on the ultrastructure of the testis of Argas (Persicargas)
      persicus (Ixodoidea: Argasidae).
AB  - Mated male Argas persicus were dissected 1 and 2 weeks after feeding on untreated
      and ivermectin (IVM)-treated pigeons. One week after feeding, testes of untreated
      ticks were filled with rounded spermatids with subplasmalemmal vesicles and
      cytoplasmic organelles, but lacking in treated ticks. Two weeks after feeding,
      testes were crowded with elongated spermatozoa supported by double-walled
      cisternal tubes. The tubes consisted of two opposite walls, each with outer
      fringed processes and inner elongated cisternae. Both were supported with
      electron dense striated plates in the middle of the spermatozoon. Internally, the
      cisternal tubes contained mitochondria and vacuoles. The nuclei were elongated
      dense masses between the tubes and the cell membranes. Subcutaneous inoculation
      of IVM at the dose 400 microg/kg pigeon resulted in extensive alterations in the
      testis of A. persicus. IVM prevented the development of new spermatids. There was
      a break down of cell membranes and cytoplasmic organelles of spermatozoa.
      Multivesicular bodies and numerous vacuoles were noticed in their cytoplasm.
      Double membranes of elongated cisternae and striation of electron dense plates
      became indistinct. IVM caused granulation and vacuolization of the nucleus as
      well as injury of mitochondrial cristae. The results suggest that IVM may bind to
      the neurotransmitter or the hormone involved in the process of sperm development
      or may be toxic to the germinal cells of A. persicus testis.

PMID- 16082930
TI  - Biology of Dermacentor silvarum (Acari: Ixodidae) under laboratory conditions.
AB  - The minimum life cycle of Dermacentor silvarum Olenev had a mean duration of 87.5
      days (range 74-102 days) under laboratory conditions [(27 +/- 1 degrees C), 70%
      RH, 6 L: 18 D]. The mean time in (days) for the different stages of its cycle was
      as follows: incubation period of eggs was 15.3 days; prefeeding, feeding and
      premoulting periods of larvae and nymphs averaged 5.5, 4.0 and 7.3 days, and 5.2,
      5.0 and 14.6 days, respectively; prefeeding, feeding, preoviposition and
      oviposition periods of female adults lasted for 7.8, 4.5, 4.3 and 14.0 days,
      respectively. There existed a highly significant correlation between engorged
      body weight of females and egg masses laid (r = 0.9877, p<0.001). The
      reproductive efficiency index (REI) and reproductive fitness index (RFI) in
      females were 11.09 and 9.58, respectively. No relationship between nymphal
      engorged body weight and resultant sexes was observed. Delayed feeding and non
      oviposition (in June and July) existed in females, and low temperature (-10
      degrees C) treatment for 45 days could terminate oviposition diapause. However,
      the egg masses laid by post-diapause females were significantly smaller than
      those laid by females engorged in March, April and May.

PMID- 16082931
TI  - The parasitism of immature stages of Ixodes loricatus (Acari: Ixodidae) on wild
      rodents in Argentina.
AB  - Ixodes loricatus has long been considered with strict-total specificity to New
      World Marsupials. However, frequent findings of its immature stages on rodents
      suggest that these vertebrates play an important role in the tick's life cycle.
      Aspects dealing with the ecology of Sigmodontinae rodents infestation by I.
      loricatus are unknown. To contribute to the knowledge of the ecology of this tick
      species, environmental factors, as well as host species, sex and age, were
      evaluated to find associations of immature I. loricatus infestation of the most
      abundant wild rodent species from riparian locations of Buenos Aires province
      (Argentina). A total of 290 hosts belonging to the subfamily Sigmodontinae were
      captured and examined for ticks at six locations. The data analysis showed that
      there was a preference of I. loricatus towards Akodon azarae, but only for those
      hosts captured in lands not prone to flooding. The results suggest that the host
      preference of I. loricatus is mainly related to factors such as habitat type and
      host density.

PMID- 16082932
TI  - Ticks (Acari: Ixodida) on wild carnivores in Brazil.
AB  - The present study reports field data of ticks infesting wild carnivores captured
      from July 1998 to September 2004 in Brazil. Additional data were obtained from
      one tick collection and from previous published data of ticks on carnivores in
      Brazil. During field work, a total of 3437 ticks were collected from 89 Cerdocyon
      thous (crab-eating fox), 58 Chrysocyon brachyurus (maned wolf), 30 Puma concolor
      (puma), 26 Panthera onca (jaguar), 12 Procyon cancrivorus (crab-eating raccoon),
      4 Speothos venaticus (bush dog), 6 Pseudalopex vetulus (hoary fox), 6 Nasua nasua
      (coati), 6 Leopardus pardalis (ocelot), 2 Leopardus tigrinus (oncilla), 1
      Leopardus wiedii (margay), 1 Herpailurus yagouaroundi (jaguarundi), 1 Oncifelis
      colocolo (pampas cat), 1 Eira barbara (tayara), 1 Galictis vittata (grison), 1
      Lontra longicaudis (neotropical otter), and 1 Potus flavus (kinkajou). Data
      obtained from the Acari Collection IBSP included a total of 381 tick specimens
      collected on 13 C. thous, 8 C. brachyurus, 3 P. concolor, 10 P. onca, 3 P.
      cancrivorus, 4 N. nasua, 1 L. pardalis, 1 L. wiedii, 4 H. yagouaroundi, 1
      Galictis cuja (lesser grison), and 1 L. longicaudis. The only tick-infested
      carnivore species previously reported in Brazil, for which we do not present any
      field data are Pseudalopex gymnocercus (pampas fox), Conepatus chinga (Molina's
      hog-nosed skunk), and Conepatus semistriatus (striped hog-nosed skunk). We report
      the first tick records in Brazil on two Felidae species (O. colocolo, H.
      yagouaroundi), two Canidae species (P. vetulus, S. venaticus), one Procyonidae
      species (P. flavus) and one Mustelidae (E. barbara). Tick infestation remains
      unreported for 5 of the 26 Carnivora species native in Brazil: Oncifelis
      geoffroyi (Geoffroy's cat), Atelocynus microtis (short-eared dog), Pteronura
      brasiliensis (giant otter), Mustela africana (Amazon weasel), and Bassaricyon
      gabbii (olingo). Our field data comprise 16 tick species represented by the
      genera Amblyomma (12 species), Ixodes (1 species), Dermacentor (1 species),
      Rhipicephalus (1 species), and Boophilus (1 species). Additional 5 tick species
      (3 Amblyomma species and 1 species from each of the genera Ixodes and
      Ornithodoros) were reported in the literature. The most common ticks on Carnivora
      hosts were Amblyomma ovale (found on 14 host species), Amblyomma cajennense (10
      species), Amblyomma aureolatum (10 species), Amblyomma tigrinum (7 species),
      Amblyomma parvum (7 species), and Boophilus microplus (7 species).

PMID- 16082933
TI  - A new record for PBDEs in people.

PMID- 16082934
TI  - Do male frogs naturally have female traits?

PMID- 16082935
TI  - Canada's research funding system works.

PMID- 16082936
TI  - Research priorities for airborne particulate matter in the United States.

PMID- 16082938
TI  - Determination of steroidal hormone profiles along the Jalle d'Eysines River (near
      Bordeaux, France).
AB  - Steroidal estrogens have been shown to be the main contributors to the estrogenic
      activity observed in aquatic systems contaminated with sewage treatment work
      effluents. Although the occurrence of steroid hormones in the environment has
      received a great deal of attention, little is known about their fate in aquatic
      systems. In the presentwork, concentrations of conjugated and unconjugated
      hormonal steroids (estrone, 17beta-estradiol, estriol, 17alpha-ethynylestradiol,
      mestranol, progesterone, norethindrone, and D-norgestrel) were determined in the
      effluent of the Eysines sewage treatment plant (near Bordeaux, France), and along
      the receiving river, the Jalle d'Eysines River. Sampling was undertaken in summer
      and in winter conditions, to study both the temporal and the spatial
      distributions of steroids in this river. Only unconjugated natural estrogens were
      detected in the effluent. Estrone was the dominant compound (detected in all
      effluent samples, 17.1-71.0 ng x L(-1)), while estradiol and its metabolite
      estriol were detected only once, at much lower levels (4.4 and 2.9 ng x L(-1),
      respectively). Levels of estrogens were clearly raised above the detection limits
      downstream of the Eysines STP effluent discharge. Seasonal variations of estrone
      degradation rates were observed. In summer, the apparent decay rates of estrogen
      levels exceeded that of dilution, indicating high removal rates from the water
      column: 50% of the initial amount of this steroid was degraded within 1.7 km
      downstream of the effluent discharge. In winter, however, estrone levels did not
      significantly decrease over a 10 km reach downstream of the effluent discharge
      (1.9-1.8 ng x L(-1)). Steroids were determined in the particulate material of the
      river, but levels were below the detection limits (0.4-1.9 ng x g(-1)),
      indicating that sorption was not a major sink of estrogens. Therefore, it is
      likely that biodegradation plays a major role in the removal of steroids from the
      river and the different decay rates are probably related to differences in
      bacterial activity within the river.

PMID- 16082937
TI  - PM2.5 of ambient origin: estimates and exposure errors relevant to PM
      epidemiology.
AB  - Epidemiological studies routinely use central-site particulate matter (PM) as a
      surrogate for exposure to PM of ambient (outdoor) origin. Below we quantify
      exposure errors that arise from variations in particle infiltration to aid
      evaluation of the use of this surrogate, rather than actual exposure, in PM
      epidemiology. Measurements from 114 homes in three cities from the Relationship
      of Indoor, Outdoor and Personal Air (RIOPA) study were used. Indoor PM2.5 of
      outdoor origin was calculated as follows: (1) assuming a constant infiltration
      factor, as would be the case if central-site PM were a "perfect surrogate" for
      exposure to outdoor particles; (2) including variations in measured air exchange
      rates across homes; (3) also incorporating home-to-home variations in particle
      composition, and (4) calculating sample-specific infiltration factors. The final
      estimates of PM2.5 of outdoor origin take into account variations in building
      construction, ventilation practices, and particle properties that result in home
      to-home and day-to-day variations in particle infiltration. As assumptions became
      more realistic (from the first, most constrained model to the fourth, least
      constrained model), the mean concentration of PM2.5 of outdoor origin increased.
      Perhaps more importantly, the bandwidth of the distribution increased. These
      results quantify several ways in which the use of central site PM results in
      underestimates of the ambient PM2.5 exposure distribution bandwidth. The result
      is larger uncertainties in relative risk factors for PM2.5 than would occur if
      epidemiological studies used more accurate exposure measures. In certain
      situations this can lead to bias.

PMID- 16082939
TI  - Is house dust the missing exposure pathway for PBDEs? An analysis of the urban
      fate and human exposure to PBDEs.
AB  - Polybrominated diphenyl ether (PBDE) body burdens in North America are 20 times
      that of Europeans and some "high accumulation" individuals have burdens up to 1-2
      orders of magnitude higher than median values, the reasons for which are not
      known. We estimated emissions and fate of sigma PBDEs (minus BDE-209) in a 470
      km2 area of Toronto, Canada, using the Multi-media Urban Model (MUM-Fate). Using
      a combination of measured and modeled concentrations for indoor and outdoor air,
      soil, and dust plus measured concentrations in food, we estimated exposure to
      sigma PBDEs via soil, dust, and dietary ingestion and indoor and outdoor
      inhalation pathways. Fate calculations indicate that 57-85% of PBDE emissions to
      the outdoor environment originate from within Toronto and that the dominant
      removal process is advection by air to downwind locations. Inadvertent ingestion
      of house dust is the largest contributor to exposure of toddlers through to
      adults and is thus the main exposure pathway for all life stages other than the
      infant, including the nursing mother, who transfers PBDEs to her infant via human
      milk. The next major exposure pathway is dietary ingestion of animal and dairy
      products. Infant consumption of human milk is the largest contributor to lifetime
      exposure. Inadvertent ingestion of dust is the main exposure pathway for a
      scenario of occupational exposure in a computer recycling facility and a fish
      eater. Ingestion of dust can lead to almost 100-fold higher exposure than
      "average" for a toddler with a high dust intake rate living in a home in which
      PBDE concentrations are elevated.

PMID- 16082940
TI  - Record of metal workshops in peat deposits: history and environmental impact on
      the Mont Lozere Massif, France.
AB  - This study aims to document the history of the metallurgical activities on the
      Mont Lozere massif in the Cevennes Mountains in Southern France. Many medieval
      sites of metallurgical wastes (slags) have been reported on the massif. These
      sites are thought to represent ancient lead workshops. The impact of past
      metallurgical activity on the environment was studied using geochemical and
      palynological techniques on a core collected in the Narses Mortes peatland near
      medieval smelting area. Two main periods of smelting activities during the last
      2200 years were revealed bythe lead concentration and isotopic composition along
      the core profile: the first period corresponds to the Gallic period
      (approximately ca. 300 B.C. to ca. 20 A.D.) and the second one to the Medieval
      period (approximately ca. 1000-1300 A.D.). Forest disturbances are associated
      with lead anomalies for the two metallurgical activities described. The impact of
      the first metallurgy was moderate during the Gallic period, during which beech
      and birch were the tree species most affected. The second period corresponds to
      the observed slag present in the field. Along with agropastoral activities, the
      medieval smelting activities led to the definitive disappearance of all tree
      species on the summit zones of Mont Lozere. The abundance of ore resources and
      the earlier presence of wood on the massif justify the presence of workshops at
      this place. The relationship between mines and ores has been documented for the
      Medieval period. There is no archaeological proof concerning the Gallic activity.
      Nevertheless, 2500-2100 years ago, the borders of the Gallic Tribe territory,
      named the Gabales, were the same as the present-day borders of the Lozere
      department. Julius Caesar reported the existence of this tribe in 58 B.C. in "De
      Bello Gallico", and in Strabon (Book IV, 2.2) the "Gabales silver" and a
      "treasure of Gabales" are mentioned, but to this day, they have not been found.

PMID- 16082941
TI  - Organic compounds produced during the thermal decomposition of cotton fabrics.
AB  - Used cotton fabrics, which can be considered a biomass according to its origin,
      were descomposed thermically in a laboratory scale reactor through a set of runs
      carried out in inert and air atmospheres, with temperatures between 650 and 1050
      degrees C. More than 90 compounds, including carbon oxides, light hydrocarbons,
      and PAHs, have been identified and quantified. In the gas phase some of the main
      components obtained were methane, ethene, and benzene. The main semivolatile
      compounds detected were styrene, phenol, naphthalene, acenaphthylene, and
      phenanthrene. Furthermore, analyses of PCDD/Fs in the material tested and in the
      semivolatile compounds produced during the combustion at 850 degrees C were also
      performed, obtaining values of 14.5 (sample) and 7.2 pg I-TEQ/g (combustion). The
      congener that mostly contributes to the total I-TEQ was 2,3,4,7,8-PeCDF. The
      results obtained show that this waste could be used as biomass, and in this way,
      it is a valid alternative to disposal in landfills.

PMID- 16082942
TI  - Deriving sediment quality guidelines from field-based species sensitivity
      distributions.
AB  - The determination of predicted no-effect concentrations (PNECs) and sediment
      quality guidelines (SQGs) of toxic chemicals in marine sediment is extremely
      important in ecological risk assessment. However, current methods of deriving
      sediment PNECs or threshold effect levels (TELs) are primarily based on
      laboratory ecotoxicity bioassays that may not be ecologically and environmentally
      relevant. This study explores the possibility of utilizing field data of benthic
      communities and contaminant loadings concurrently measured in sediment samples
      collected from the Norwegian continental shelf to derive SQGs. This unique
      dataset contains abundance data for ca. 2200 benthic species measured at over
      4200 sampling stations, along with co-occurring concentration data for >25
      chemical species. Using barium, cadmium, and total polycyclic aromatic
      hydrocarbons (PAHs) as examples, this paper describes a novel approach that makes
      use of the above data set for constructing field-based species sensitivity
      distributions (f-SSDs). Field-based SQGs are then derived based on the f-SSDs and
      HCx values [hazardous concentration for x% of species or the (100-x)% protection
      level] by the nonparametric bootstrap method. Our results for Cd and total PAHs
      indicate that there are some discrepancies between the SQGs currently in use in
      various countries and our field-data-derived SQGs. The field-data-derived
      criteria appear to be more environmentally relevant and realistic. Here, we
      suggest that the f-SSDs can be directly used as benchmarks for probabilistic risk
      assessment, while the field-data-derived SQGs can be used as site-specific
      guidelines or integrated into current SQGs.

PMID- 16082943
TI  - Transport of chemical and microbial compounds from known wastewater discharges:
      potential for use as indicators of human fecal contamination.
AB  - The quality of drinking and recreational water is currently (2005) determined
      using indicator bacteria. However, the culture tests used to analyze forthese
      bacteria require a long time to complete and do not discriminate between human
      and animal fecal material sources. One complementary approach is to use chemicals
      found in human wastewater, which would have the advantages of (1) potentially
      shorter analysis times than the bacterial culture tests and (2) being selected
      for human-source specificity. At 10 locations, water samples were collected
      upstream and at two successive points downstream from a wastewaster treatment
      plant (WWTP); a treated effluent sample was also collected at each WWTP. This
      sampling plan was used to determine the persistence of a chemically diverse suite
      of emerging contaminants in streams. Samples were also collected at two reference
      locations assumed to have minimal human impacts. Of the 110 chemical analytes
      investigated in this project, 78 were detected at least once. The number of
      compounds in a given sample ranged from 3 at a reference location to 50 in a WWTP
      effluent sample. The total analyte load at each location varied from 0.018
      microg/L at the reference location to 97.7 microg/L in a separate WWTP effluent
      sample. Although most of the compound concentrations were in the range of 0.01
      1.0 microg/L, in some samples, individual concentrations were in the range of 5
      38 microg/L. The concentrations of the majority of the chemicals present in the
      samples generally followed the expected trend: they were either nonexistent or at
      trace levels in the upstream samples, had their maximum concentrations in the
      WWTP effluent samples, and then declined in the two downstream samples. This
      research suggests that selected chemicals are useful as tracers of human
      wastewater discharge.

PMID- 16082944
TI  - Typical dioxin concentrations in agriculture soils of Washington state and
      potential sources.
AB  - Background or typical levels of polychlorinated dibenzo-p-dioxins and of
      polychlorinated dibenzo-p-furans in soils have become increasingly important in
      the regulatory community, as dioxins have come under increased scrutiny due to
      their toxicity and persistence. Knowing the typical levels of dioxin in soils is
      important to set regulatory levels, to prevent further contamination, and for
      setting cleanup levels. A random sample (n=54) of agricultural lands within
      Washington state revealed a typical concentration of "dioxin" of 0.14 ng/kg
      (toxicity equivalents, TEQ). For a comparison, residential urban areas, forested,
      and open areas were also investigated on a smaller scale (n=14, 8, and 8,
      respectively) with typical dioxin values of 4.1, 2.3, and 1.0 ng/kg (TEQs),
      respectively. A discriminant function analysis was used to examine soil dioxin
      profiles and associations with potential known dioxin sources in Washington
      state. Soil sample dioxin profiles could not be discriminated from those of
      biosolids and pentachlorophenol products.

PMID- 16082945
TI  - Polybrominated diphenyl ethers and polychlorinated biphenyls in human adipose
      tissue from New York.
AB  - Human adipose tissue samples (n=52) collected in New York City during 2003-2004
      were analyzed for the presence of polybrominated diphenyl ethers (PBDEs) and
      polychlorinated biphenyls (PCBs). Concentrations of PBDEs in adipose tissues
      ranged from 17 to 9630 ng/g, lipid wt (median: 77; mean: 399 ng/g, lipid wt; sum
      all di- through hexaBDE congeners). Average PBDE concentrations in human adipose
      tissues from New York City were 10- to 100-times greater than those reported for
      European countries. A concentration of 9630 ng/g, lipid wt, found in a sample of
      adipose tissue, is one of the highest concentrations reported to date. PBDE 47
      (2,2',4,4'-tetraBDE) was the major congener detected in human tissues, followed
      by PBDE congeners #99 (2,2',4,4',5-penta BDE), 100 (2,2',4,4',6-pentaBDE), and
      153 (2,2',4,4',5,5'-hexaBDE). A few individuals contained PBDE 153 as the
      predominant congener in total PBDE concentrations, suggesting alternative
      exposure sources, possibly occupational. Principal component analysis of PBDE
      congener composition in human adipose tissues revealed the presence of five
      clusters, each characterized by varying composition. No significant difference
      was found in the concentrations of PBDEs between gender. Concentrations of PBDEs
      were, on average, similar to those for PCBs in human adipose tissues, and
      substantially higher when PBDE outliers were retained. PBDE and PCB
      concentrations were not correlated. PBDE concentrations did not increase with
      increasing age of the subjects, whereas concentrations of PCBs increased with
      increasing age in males but not in females in this study. These results suggest
      differences between PBDEs and PCBs in their sources or time course of exposure
      and disposition. The presence of comparable or greater concentrations of PBDEs,
      relative to PCBs, highlights the importance of recentvoluntary and regulatory
      effortsto cease production of commercial penta- and octa-BDE in North America,
      although these efforts do not address continuing emissions from existing sources,
      such as polyurethane foams.

PMID- 16082946
TI  - Perchlorate affects thyroid function in eastern mosquitofish (Gambusia holbrooki)
      at environmentally relevant concentrations.
AB  - The purpose of this study was to determine the effects of perchlorate on thyroid
      function in mosquitofish. Adult mosquitofish were exposed to 0, 0.1, 1, 10, 100,
      and 1000 mg/L sodium perchlorate for 2, 10, and 30 d. Whole body thyroxin (T4)
      content and histological assessment of thyroid follicles (e.g., follicular
      epithelial height, hyperplasia, hypertrophy, and colloid depletion) were used to
      gauge alterations in thyroid function. Follicular epithelial cell height,
      hyperplasia, and hypertrophy increased with increasing perchlorate concentration,
      especially in fish exposed for 30 d, and these effects were statistically
      significantly different from control at concentrations as low as 0.1 mg/L
      (nominal concentration). The percent occurrence of follicles with depleted
      colloid decreased with increasing perchlorate concentration, which is contrary to
      what is expected with thyroid inhibition. There also was a decrease in whole body
      T4 concentration in fish exposed to perchlorate for 30 d, but clear dose-response
      relationships were less evident for whole body T4 than for histopathological
      endpoints. In conclusion, thyroid histopathology provides a sensitive biomarker
      for thyroid endocrine disruption at environmentally relevant concentrations of
      sodium perchlorate, and whole body T4 is a less sensitive indicator of
      perchlorate exposure than is histopathology.

PMID- 16082947
TI  - Three-dimensional mapping of oxygen distribution in wastewater biofilms using an
      automation system and microelectrodes.
AB  - The three-dimensional oxygen distribution in wastewater biofilms was evaluated
      using combined oxygen microelectrodes and an automation system. The biofilms were
      sampled from rotating biological contactors treating domestic wastewater. The
      samples studied were mature biofilms with a thickness from 630 to 1600 microm. It
      was demonstrated that the dissolved oxygen concentration could be depleted at the
      biofilm surface. The heterogeneity of the dissolved oxygen distribution was high
      in sections further away from the biofilm surface in the water layer. The study
      showed that the concentration and level of heterogeneity of dissolved oxygen
      inside the biofilms decreased with depth, forming stratification. The oxygen
      concentration in biofilms changed generally from a high degree of heterogeneity
      near the biofilm surface to a low degree of heterogeneity in deep sections of
      biofilms, indicating a cell--cluster-like structure near the surface and more
      compact base layer close to the substratum. The three-dimensional oxygen
      distribution maps revealed pockets of dissolved oxygen in deep sections of
      biofilms. The dissolved oxygen concentrations of these pockets in the biofilm
      samples ranged from 0.4 to 1.0 mg/L at 760 microm depth. The three-dimensional
      oxygen distribution maps produced relevant knowledge of functional and structural
      characteristics of biofilms used for the treatment of wastewater.

PMID- 16082948
TI  - Multiphase decomposition of novel oxygenated organics in aqueous and organic
      media.
AB  - Prior to the massive use of new oxygenated solvents, data on their multiphase
      reactivity must be obtained to assess their environmental fate and impact on
      water and air quality. For this, the kinetics and mechanisms of the photochemical
      and photocatalytic degradation of selected oxygenated solvents by common
      tropospheric oxidants (such as OH and ozone) must be characterized. We studied
      the oxidation kinetics of new oxygenated solvents as pure organic liquids and in
      an aqueous medium by ozone and bythe OH radical, respectively. The studied
      chemicals are all unsaturated compounds, having none, one, or two ether groups.
      The results indicate that the OH reaction proceeds atthe diffusion limit by
      addition to the double bond. The reactive uptake coefficients associated with the
      reaction initiated by ozone are of the order of 10(-3). The reactions of
      compounds with two double bonds are very fast and probably occur at the surface.
      This kinetic information demonstrates that organic solvents in an organic medium
      or in an aqueous droplet will be oxidized rapidly by these oxidation reactions.
      These reactions, however, are not significant sinks for ozone and OH radicals.

PMID- 16082949
TI  - Environmental fate of pharmaceuticals in water/sediment systems.
AB  - In recent years there has been growing interest on the occurrence and the fate of
      pharmaceuticals in the aquatic environment. Nevertheless, few data are available
      covering the fate of the pharmaceuticals in the water/sediment compartment. In
      this study, the environmental fate of 10 selected pharmaceuticals and
      pharmaceutical metabolites was investigated in water/sediment systems including
      both the analysis of water and sediment. The experiments covered the application
      of four 14C-labeled pharmaceuticals (diazepam, ibuprofen, iopromide, and
      paracetamol) for which radio-TLC analysis was used as well as six nonlabeled
      compounds (carbamazepine, clofibric acid, 10,11-dihydro-10,11
      dihydroxycarbamazepine, 2-hydroxyibuprofen, ivermectin, and oxazepam), which were
      analyzed via LC-tandem MS. Ibuprofen, 2-hydroxyibuprofen, and paracetamol
      displayed a low persistence with DT50 values in the water/sediment system < or
      =20 d. The sediment played a key role in the elimination of paracetamol due to
      the rapid and extensive formation of bound residues. A moderate persistence was
      found for ivermectin and oxazepam with DT50 values of 15 and 54 d, respectively.
      Lopromide, for which no corresponding DT50 values could be calculated, also
      exhibited a moderate persistence and was transformed into at least four
      transformation products. For diazepam, carbamazepine, 10,11-dihydro-10,11
      dihydroxycarbamazepine, and clofibric acid, system DT90 values of >365 d were
      found, which exhibit their high persistence in the water/sediment system. An
      elevated level of sorption onto the sediment was observed for ivermectin,
      diazepam, oxazepam, and carbamazepine. Respective Koc values calculated from the
      experimental data ranged from 1172 L x kg(-1) for ivermectin down to 83 L x kg(
      1) for carbamazepine.

PMID- 16082950
TI  - Solar radiation, relative humidity, and soil water effects on metolachlor
      volatilization.
AB  - Pesticide volatilization is a significant loss pathway that may have unintended
      consequences in nontarget environments. Field-scale pesticide volatilization
      involves the interaction of a number of complex variables. There is a need to
      acquire pesticide volatilization fluxes from a location where several of these
      variables can be held constant. Accordingly, soil properties, tillage practices,
      surface residue management, and pesticide formulations were held constant while
      fundamental information regarding metolachlor volatilization (a pre-emergent
      pesticide) was monitored over a five-year period as influenced by meteorological
      variables and soil water content. Metolachlor vapor concentrations were measured
      continuously for 120 h after each application using polyurethane foam plugs in a
      logarithmic profile above the soil surface. A flux gradient technique was used to
      compute volatilization fluxes from metolachlor concentration profiles and
      turbulent fluxes of heat and water vapor (as determined from eddy covariance
      measurements). Differences in meteorological conditions and surface soil water
      contents resulted in variability of the volatilization losses over the years
      studied. The peak volatilization losses for each year occurred during the first
      24 h after application with a maximum flux rate in 2001 (1500 ng m(-2) s(-1))
      associated with wet surface soil conditions combined with warm temperatures. The
      cumulative volatilization losses for the 120-hour period following metolachlor
      application varied over the years from 5 to 25% of the applied active ingredient,
      with approximately 87% of the losses occurring during the first 72 h. In all of
      the years studied, volatilization occurred diurnally and accounted for between 43
      and 86% during the day and 14 and 57% during the night of the total measured
      loss. The results suggest that metolachlor volatilization is influenced by
      multiple factors involving meteorological, surface soil, and chemical factors.

PMID- 16082951
TI  - Mineralization of organic sulfur delays recovery from anthropogenic
      acidification.
AB  - While SO4(2-) concentrations in runoff are decreasing in many catchments in
      Europe, present day S output still exceeds the S input for most forested
      catchments in Europe and North America. Here we report that a large part of the
      observed SO4(2-) in the runoff at a large-scale catchment study site (the
      Gardsjon roof experiment in southwestern Sweden) originates from the organic S
      pool in the O horizon. Budget estimates comparing soil S pools showed reductions
      in the S pool of 57 mmol of S m(-2) in the O horizon and 26 mmol of SO4(2-) m(-2)
      in the mineral Bs horizon after excluding anthropogenic deposition for four
      years. There was an increase of about 1% per hundred in the delta34S(SO4), value
      of the mineral soil SO4(2-) between 1990 and 1995 (average and 95% confidence
      interval of 6.2 +/- 0.6 and 7.7 +/- 0.6% per hundred, respectively), but the
      delta34S(SO4) values in the E horizon are still much lower than the sprinkler
      water input of +19.7% per hundred, although the horizon has only a small
      extractable SO4(2-) pool. After nine years (1991-2000) of artificially supplying
      S inputs comparable with those amounts supplied by preindustrial rain, the amount
      of S in runoff still exceeded the input by 30%. This extra 30% corresponds to a
      loss of 3 mmol of S m(-2) year(-1), compared to the soil S organic O horizon pool
      of 1098 mmol m(-2) in 1990, suggesting that recovery is delayed for decades, at
      least.

PMID- 16082952
TI  - Comparison of a chemical and enzymatic extraction of arsenic from rice and an
      assessment of the arsenic absorption from contaminated water by cooked rice.
AB  - Rice is a target food for arsenic speciation based analyses because of its
      relatively high arsenic concentration and per capita consumption rates. Improved
      speciation data for rice can be helpful in estimating inorganic arsenic exposures
      in the U.S. and in endemic populations. The inorganic arsenic exposure for cooked
      rice should include both the arsenic in raw rice plus the arsenic absorbed from
      the water used to prepare it. The amount of arsenic absorbed from water by rice
      during preparation was assessed using five different types of rice cooked in both
      contaminated drinking water and arsenic-free reagent water. The rice samples were
      extracted using trifluoroacetic acid (TFA) and speciated using IC-ICP-MS. The TFA
      procedure was able to extract 84-104% of the arsenic (As) from the five different
      cooked rice samples. Chromatographic recoveries ranged from 99% to 116%. The
      dimethylarsinic acid (DMA) and inorganic arsenic concentration ranged from 22 to
      270 ng of As/g of rice and from 31 to 108 ng of As/g of rice, respectively, for
      samples cooked in reagent water. The overall recoveries, which relate the sum of
      the chromatographic species back to the total digested concentration, ranged from
      89% to 117%. The absorption of arsenic by rice from the total volume of water
      [1:1 to 4:1 (water:rice)] used in cooking was between 89% and 105% for two
      different contaminated drinking water samples. A comparison of the TFA extraction
      to an enzymatic extraction was made using the five rice samples and NIST 1568a
      rice flour. The two extraction procedures produced good agreement for inorganic
      arsenic, DMA, and the overall recovery. Through the use of IC-ESI-MS/ MS with a
      parent ion of m/z 153 and fragment ions of m/z 138, 123, and 105, the structure
      dimethylthioarsinic acid was tentatively identified in two of the rice samples
      using the enzymatic extraction.

PMID- 16082953
TI  - Calcium-(organo)aluminum-proton competition for adsorption to tomato root cell
      walls: experimental data and exchange model calculations.
AB  - Aluminum interacts with negatively charged surfaces in plant roots, causing
      inhibition of growth and nutrient uptake in plants growing on acid soils. Pectins
      in the root cell wall form the major cation adsorption surface, with Ca2+ as the
      main adsorbing cation. Adsorption of Al3+ and Ca2+ to isolated cell wall material
      of tomato (Lycopersicon esculentum L.) roots was examined at pH 3.00-4.25 and in
      the presence of the aluminum chelators citrate and malate. Al3+ displaced Ca2+
      from its pectic binding sites in the cell wall to a large extent but apparently
      also bound to non-Ca binding groups, displacing protons. Aluminum adsorption
      depended on the pH of the solution, with little Al adsorbing to the cell wall
      material at very low pH (<3.50). Under very acid conditions Al3+ replacing Ca2+
      at pectic cross-links is therefore not expected to play a role in Al toxicity.
      Equimolar concentrations of citrate decreased Al competition for Ca binding sites
      almost completely, whereas malate only had an intermediate effect. The
      competition of (organo) Al3+, Ca2+, and H+ for cell wall binding sites was
      described adequately using the Gaines-Thomas exchange model.

PMID- 16082954
TI  - Gonadal development of larval male Xenopus laevis exposed to atrazine in outdoor
      microcosms.
AB  - The potential effects of atrazine on gonadal development in metamorphs and
      subadults of the African clawed frog (Xenopus laevis) were studied under
      conditions of natural photoperiod and temperatures in outdoor microcosms from
      August 2002 to June 2003 in South Africa. Triplicate 1100 L microcosms for each
      nominal concentration of 0.0, 1, 10, and 25 microg of atrazine/L were used.
      Measured atrazine concentrations varied <25% throughout the study, and no
      atrazine was detected in the control microcosms. Tadpoles developed well at all
      concentrations. On the basis of histological examination of testes of recently
      metamorphosed stage 66 frogs, 57% of the individuals in the reference group
      exhibited testicular oocytes as compared with 57, 59, and 39% of the 1, 10, and
      25 microg/L atrazine groups, respectively. The average prevalence of testicular
      oocytes for all of the treatments including the controls was 54% in a single
      testis, while, in 35% of individuals, testicular oocytes were observed in both
      testes. The number of testicular oocytes per individual ranged from 0 to 58 with
      means of 9.5, 9.8, 8.5, and 11.1 forthe 0.0, 1, 10, and 25 microg of atrazine/L
      groups, respectively. Ten months after metamorphosis, another subset of juveniles
      was examined, and the maximum number of testicular oocytes observed was five in
      one animal. The presence of testicular oocytes was not related to exposure to
      atrazine and may be a natural phenomenon during ontogeny.

PMID- 16082955
TI  - Electricity generation from artificial wastewater using an upflow microbial fuel
      cell.
AB  - The upflow microbial fuel cell (UMFC) was developed to generate electricity while
      simultaneously treating wastewater. During a five-month period of feeding a
      sucrose solution as the electron donor, the UMFC continuously generated
      electricity with a maximum power density of 170 mW/m2. To achieve this power
      density, the artificial electron-mediator hexacyanoferrate was required in the
      cathode chamber. The power density increased with increasing chemical oxygen
      demand (COD) loading rates up to 2.0 g COD/ L/day after which no further
      increases in power density were observed, indicating the presence of limiting
      factors. The overarching limiting factor for the UMFC in this study was the
      internal resistance, which was estimated as 84 omega at the maximum power
      density, and restricted the power output by causing a significant decrease in
      operating potential. Low Coulombic efficiencies varying from 0.7 to 8.1% implied
      that the electron-transfer bacteria were incapable of converting all of the
      available organics into electricity, so the excessive substrate created niches
      for the growth of methanogens. We found that the soluble COD (SCOD) removal
      efficiencies remained over 90% throughout the operational period, mainly because
      of methanogenic activity, which accounted for 35 to 58% of the SCOD removed at a
      loading rate of 1.0 g COD/L/ day. Additionally, transport limitation due to
      insufficient substrate diffusion was shown by cyclic voltammetry (CV).

PMID- 16082956
TI  - Natural humics impact uranium bioreduction and oxidation.
AB  - Although humic substances occur ubiquitously in soil and groundwater, their
      effect on the biological reduction of uranium(VI) and subsequent reoxidation of
      U(IV) is poorly understood. This study investigated the role of humics in
      enhancing the bioreduction of U(VI) in laboratory kinetic studies, in field push
      pull tests, and in the presence or absence of metal ions such as Ca2+ and Ni2+,
      which are known to inhibit the biological reduction of U(VI). Results from
      laboratory experiments indicate that, under strict anaerobic conditions, the
      presence of humic materials enhanced the U(VI) reduction rates (up to 10-fold)
      and alleviated the toxicity effect of Ni2+ on microorganisms. Humic acid was
      found to be more effective than fulvic acid in enhancing the reduction of U(VI).
      Such an enhancement effect is attributed to the ability of these humics in
      facilitating electron-transfer reactions and/or in complexing Ca2+ and Ni2+ ions.
      Similarly, field push-pull tests demonstrated a substantially increased rate of
      U(VI) reduction when humic acid was introduced into the site groundwater.
      However, humics were also found to form complexes with reduced U(IV) and
      increased the oxidation of U(IV) (when exposed to oxygen) with an oxidation
      halflife on the order of a few minutes. Both of these processes render uranium
      soluble and potentially mobile in groundwater, depending on site-specific and
      dynamic geochemical conditions. Future studies must address the stability and
      retention of reduced U(IV) under realistic field conditions (e.g., in the
      presence of dissolved oxygen and low concentrations of complexing organics).

PMID- 16082957
TI  - On-road emission rates of PAH and n-alkane compounds from heavy-duty diesel
      vehicles.
AB  - This paper presents the quantification of the emission rates of PAH and n-alkane
      compounds from on-road emissions testing of nine heavy-duty diesel (HDD) vehicles
      tested using CE-CERT's Mobile Emissions Laboratory (MEL) over the California Air
      Resources Board (ARB) Four Phase Cycle. Per mile and per CO2 emission rates of
      PAHs and n-alkanes were highest for operation simulating congested traffic
      (Creep) and lowest for cruising conditions (Cruise). Significant differences were
      seen in emission rates over the different phases of the cycle. Creep phase fleet
      average emission rates (mg mi(-1)) of PAHs and n-alkanes were approximately an
      order of magnitude higher than Cruise phase. This finding indicates that models
      must account for mode of operation when performing emissions inventory estimates.
      Failure to account for mode of operation can potentially lead to significant over
      and underpredictions of emissions inventories (up to 20 times), especially in
      small geographic regions with significant amounts of HDD congestion. Howeverthe
      PAH and n-alkane source profiles remained relatively constant for the different
      modes of operation. Variability of source profiles within the vehicle fleet
      exceeded the variability due to different operating modes. Analysis of the
      relative risk associated with the compounds indicated the importance of
      naphthalene as a significant contributor to the risk associated with diesel
      exhaust. This high relative risk is driven by the magnitude of the emission rate
      of naphthalene in comparison to other compounds.

PMID- 16082958
TI  - Impact of vegetation on sedimentary organic matter composition and polycyclic
      aromatic hydrocarbon attenuation.
AB  - Results from natural and engineered phytoremediation systems provide strong
      evidencethatvegetated soils mitigate polycyclic aromatic hydrocarbon (PAH)
      contamination. However, the mechanisms by which PAH mitigation occurs and the
      impact of plant organic matter on PAH attenuation remain unclear. This study
      assessed the impact of plant organic matter on PAH attenuation in labile and
      refractory sediments fractions from a petroleum distillate waste pit that has
      naturally revegetated. Samples were collected in distinct zones of barren and
      vegetated areas to assess changes to organic matter composition and PAH content
      as vegetation colonized and became established in the waste pit. Sediments were
      fractionated into bulk sediment and humin fractions and analyzed for organic
      matter composition by isotope ratio mass spectrometry (delta (13)C), 13C nuclear
      magnetic resonance (13C NMR), delta 14C AMS (accelerator mass spectrometry), and
      percent organic carbon (%TOC). Gas chromatography mass spectrometry (GC/ MS) of
      lipid extracts of SOM fractions provided data for PAH distribution histograms,
      compound weathering ratios, and alkylated and nonalkylated PAH concentrations.
      Inputs of biogenic plant carbon, PAH weathering, and declines in PAH
      concentrations are most evidentfor vegetated SOM fractions, particularly humin
      fractions. Sequestered PAH metabolites were also observed in vegetated humin.
      These results show that plant organic matter does impact PAH attenuation in both
      labile and refractory fractions of petroleum distillate waste.

PMID- 16082959
TI  - Influence of agricultural biomass burning on aerosol size distribution and dry
      deposition in southeastern Brazil.
AB  - The size distributed composition of ambient aerosols is used to explore seasonal
      differences in particle chemistry and to show that dry deposition fluxes of
      soluble species, including important plant nutrients, increase during periods of
      biomass (sugar cane trash) burning in Sao Paulo State, Brazil. Measurements were
      made at a single site centrally located in the State's sugar cane growing region
      but away from the immediate vicinity of burns, so that the airsampled was
      representative of the regional background. Calculation of ion equivalent balances
      showed that during burning periods smaller particles (Aitken and accumulation
      modes) were more acidic, containing higher concentrations of SO4(2-), oxalate,
      NO3-, HCOO-, CH3COO-, and CI-, but insufficient NH4+ and K+ to achieve
      neutrality. Larger particles showed an anion deficit due to the presence of
      unmeasured ions and comprised resuspended dusts modified by accumulation of
      nitrate, chloride, and organic anions. Increases of resuspended particles during
      the burning season were attributed to release of earlier deposits from the
      surfaces of burning vegetation as well as increased vehicle movement on
      unsurfaced roads. During winter months the relative contribution of combined
      emissions from road transport and industry diminished due to increased emissions
      from biomass combustion and other activities specifically associated with the
      harvest period. Positive increments in annual particulate dry deposition fluxes
      due to higher fluxes during the sugar cane harvest were 44.3% (NH4+), 42.1% (K+),
      31.8% (Mg2+), 30.4% (HCOO-), 12.8% (CI-), 6.6% (CH3COO-), 5.2% (Ca2+), 3.8%
      (SO4(2-)), and 2.3% (NO3-). Na+ and oxalate fluxes were seasonally invariant.
      Annual aerosol dry deposition fluxes (kg ha(-1)) were 0.5 (Na+), 0.25 (NH4+),
      0.39 (K+), 0.51 (Mg2+), 3.19 (Ca2+), 1.34 (Cl-), 4.47 (NO3-), 3.59 (SO4(2-)),
      0.58 (oxalate), 0.71 (HCOO-), and 1.38 (CH3COO-). Contributions of this mechanism
      to combined aerosol dry deposition and precipitation scavenging (inorganic
      species, excluding gaseous dry deposition) were 31% (Na+), 8% (NH4+), 26% (K+),
      63% (Mg2+), 66% (Ca2+), 32% (Cl-), 33% (NO3-), and 36% (SO4(2-)).

PMID- 16082960
TI  - Reactions of chlorine atoms with a series of aromatic hydrocarbons.
AB  - Aromatic hydrocarbons, including polycyclic aromatic hydrocarbons (PAHs), are
      present in urban and rural atmospheres. Reactions of PAHs with Cl atoms may occur
      in the marine boundary layer and in coastal regions. To assess the importance of
      these reactions and to investigate whether any unique chlorine-containing
      products are formed from these reactions, we have measured the rate constants for
      the gas-phase reactions of Cl atoms with toluene-d8, 1,3,5-trimethylbenzene
      (1,3,5-TMB), naphthalene, 1-methylnaphthalene-d10 (1-MN-d10), 1- and 2
      methylnaphthalene (1- and 2-MN), 1- and 2-ethylnaphthalene (1- and 2-EN), and the
      dimethylnaphthalenes (DMNs) at 296 +/- 2 K. A relative rate technique was used,
      and, using our measured rate constant forthe reaction of Cl atoms with 1,3,5-TMB
      of 2.42 x 10(-10) cm3 molecule(-1) s(-1), the rate constants (in units of 10(-10)
      cm3 molecule(-1) s(-1)) are as follows: naphthalene, < or = 0.0091 +/- 0.0003; 1
      MN, 1.21 +/- 0.16; 2-MN, 1.05 +/- 0.13; 1-EN, 2.12 +/- 0.35; 2-EN, 1.38 +/- 0.27;
      1,2-DMN, 3.61 +/- 0.68; 1,3-DMN, 2.90 +/- 0.22; 1,4-DMN, 2.93 +/- 0.30; 1,5-DMN,
      2.31 +/- 0.19; 1,6-DMN, 2.15 +/- 0.20; 1,7-DMN, 3.05 +/- 0.34; 1,8-DMN, 3.07 +/-
      0.44; 2,3-DMN, 2.93 +/- 0.49; 2,6-DMN, 2.34 +/- 0.18; and 2,7-DMN, 2.00 +/- 0.22,
      where the indicated errors are two standard deviations and do not include the
      uncertainty in the rate constant for 1,3,5-TMB. The measured deuterium isotope
      effects for the toluene-d8 and 1-MN-d10 reactions indicate that the reactions
      proceed by initial H- (or D-) atom abstraction. The products identified and
      quantified from the toluene and 1-MN reactions using gas chromatography and in
      situ direct air sampling atmospheric pressure ionization tandem mass spectrometry
      were benzaldehyde (84% +/- 7% yield) and benzyl alcohol (11% +/- 2% yield) from
      toluene and 1-naphthaldehyde (approximately 36%, lower limit to yield) and 1
      naphthyl alcohol (approximately 12%, lower limit to yield) from 1-MN. These
      products confirm that H-atom abstraction is the dominant, if not sole, reaction
      pathway for the alkylbenzenes and alkylnaphthalenes, consistent with the 100-fold
      lower rate constant measured for naphthalene compared to the alkylnaphthalenes
      and with the measured deuterium isotope effects.

PMID- 16082961
TI  - Formation and dissolution of single and mixed Zn and Ni precipitates in soil:
      evidence from column experiments and extended X-ray absorption fine structure
      spectroscopy.
AB  - The stability and the formation and dissolution kinetics of mixed trace metal
      precipitates in soils are currently unknown. The objective of this study was to
      investigate slow sorption and release processes of Zn and Ni in a loamy soil
      using a combination of soil column experiments and extended X-ray absorption fine
      structure (EXAFS) spectroscopy. To investigate slow sorption processes, the soil
      material was packed into columns and leached with 5400 pore volumes of 10(-2) M
      CaCl2 solutions containing either ZnCl2 (5.2 x 10(-5) M) or NiCl2 (5.2 x 10(-5)
      M) or both ZnCl2 and NiCl2 (5.2 x 10(-5) M each). The Zn and Ni concentrations in
      the column effluents were monitored. The metal breakthrough curves showed that
      slow sorption processes lead to metal retention, whereby Zn was more strongly
      retained than Ni. In the experiment with both Zn and Ni present, amounts of Zn
      and Ni similar to those in the experiments with either Zn or Ni alone were
      retained. Analysis of soil samples by EXAFS spectroscopy showed that layered
      double hydroxide (LDH)-type precipitates had formed in all columns and that a
      mixed ZnNi-LDH had formed in the presence of both Zn and Ni. The dissolution of
      those precipitates under acidic conditions was assessed by subsequent leaching of
      the columns with a 10(-2) M CaCl2 solution at pH 3.0 (approximately 3000 pore
      volumes). When only Zn was present, 95% of the retained Zn was leached at pH 3.
      In contrast, only 23% of the retained Ni was leached in experiments with Ni
      alone. When Zn and Ni were present, 90% of the retained Zn and 87% of the
      retained Ni were released upon acidification. EXAFS analysis revealed that the
      LDH phases in the Zn experiment and the Zn-Ni experiment had been completely
      dissolved, while the LDH phase formed in the Ni experiment was still present. The
      higher resistance of Ni-LDH against dissolution at low pH could also be shown in
      dissolution studies with synthetic Zn-LDH, Ni-LDH, and ZnNi-LDH. Our results
      suggest that the individual rates at which Zn and Ni cations enter into the LDH
      structure determine the composition of the mixed ZnNi-LDH precipitate, and that
      the LDH composition determines the rate at which the LDH phase dissolves under
      acidic conditions.

PMID- 16082962
TI  - Effect of humic and fulvic acid concentrations and ionic strength on copper and
      lead binding.
AB  - We investigated the influence of humic and fulvic acid concentration (in the
      range of 1-1000 mg/L) on the binding of the two trace metals Cu(II) and Pb(II).
      The ability of the non-ideal competitive adsorption (NICA)-Donnan model to
      correctly predict Cu and Pb binding at low humic or fulvic acid concentration and
      lower ionic strength (0.01 M NaNO3), based on model parameters obtained from
      experiments conducted at high humic or fulvic acid concentrations (approximately
      1000 mg/L) and higher ionic strength (0.1 M NaNO3), was tested. The binding of Cu
      and Pb to humic and fulvic acid in 0.01 M NaNO3 was determined over wide ranges
      in proton and metal ion activities using three different methods: ligand exchange
      adsorptive differential pulse cathodic stripping voltammetry at low humic or
      fulvic acid concentrations (1-3 mg/L), differential pulse anodic stripping
      voltammetry at intermediate humic or fulvic acid concentrations (10-20 mg/L), and
      ion-selective electrodes at high humic or fulvic acid concentrations
      (approximately 1000 mg/L). The results demonstrate that binding isotherms for Cu
      and Pb can be measured at low humic or fulvic acid concentration using suitable
      voltammetric techniques. The binding isotherms for Cu and Pb to humic and fulvic
      acid obtained at constant pH values in the range of pH 4-8 are shown to be
      independent of humic and fulvic acid concentration. The NICA-Donnan model,
      calibrated for Cu and Pb binding using data measured at high humic and fulvic
      acid concentrations and an ionic strength of 0.1 M, accurately predicts Cu and Pb
      binding at low humic and fulvic acid concentrations and lower ionic strength
      (0.01 M). We conclude that NICA-Donnan parameters obtained by fitting
      experimental data measured with ion-selective electrodes at high humic or fulvic
      acid concentrations can be used for geochemical modeling of soils and aquatic
      environments with much lower concentrations of humic or fulvic acids.

PMID- 16082963
TI  - Hierarchical responses of soil invertebrates (earthworms) to toxic metal stress.
AB  - The concept of a hierarchical cascade of biological responses to stress occurring
      across different levels of biological organization is an underlying principle of
      both theoretical and regulatory ecology/ecotoxicology. This study investigates
      the reality of this cascade for earthworms exposed to toxic metal stress. Gene
      expression was the most sensitive endpoint (EC50 = 616 microg Zn g(-1)) followed
      by the integrity of coelomocyte lysosomal membrane (EC50 = 645 microg Zn g(-1)).
      This confirms that, in accordance with the cascade concept, suborganism level
      endpoints respond at lower metal concentrations than higher organization
      endpoints. The relative sensitivity of the higher organization parameters was not
      as predicted by the cascade. Organic material removal was more sensitive (EC50 =
      997 microg Zn g(-1)) than L. rubellus reproduction (EC50 = 3236 microg Zn g(-1)),
      L. rubellus population size (EC50 = 5000-11500 microg Zn g(-1)), and earthworm
      community diversity (EC50 = 1737 microg Zn g(-1)). This can be attributed to (1)
      the relative insensitivity of L. rubellus to metals and (2) general toxic effects
      of metals on the earthworm energy budget (and thus feeding). On the basis of
      these results, it can be concluded that predictive assessments of the
      consequences of environmental stressors needs to include approaches that respect
      the relative sensitivities of different taxa, while retrospective appraisals
      should exploit the sensitivity of low organization level responses.

PMID- 16082964
TI  - Photoinduced oxidation of antimony(III) in the presence of humic acid.
AB  - Interactions of antimony with natural organic matter (NOM) are important for the
      fate of Sb in aquatic systems. The kinetics of the photosensitized oxidation of
      Sb(III) to Sb(V) in the presence of Suwannee River Humic Acid (SRHA) was
      investigated using UV-A and visible light (medium-pressure mercury lamp). At a
      concentration of 5 mg L(-1) dissolved organic carbon (DOC) the light-induced
      reaction was 9000 times faster (rate coefficient k(exp) = 7.0 +/- 0.05 x 10(-4)
      s(-1)) than the dark reaction and followed pseudo-first-order kinetics. Rates
      increased linearly with the concentration of DOC. Between pH 4 and 8 rates
      increased by a factor of 5. Further results and kinetic considerations indicate
      that singlet oxygen, hydroxyl radicals, hydrogen peroxide, and hydroperoxyl
      radicals/superoxide are not important photooxidants in this system, while other
      NOM-derived reactive species, in particular excited triplet states and/or
      phenoxyl radicals, seem to be relevant. The dependence of rate coefficients on
      Sb(III)/DOC ratio was consistent with a two binding site model including (i) a
      strong binding site at low concentration inducing fast oxidation, (ii) a weak
      binding site at high concentration inducing slower oxidation, and (iii) the even
      slower oxidation of Sb(OH)3. Photoirradiation of natural water samples spiked
      with Sb(III) showed that the oxidation rates could be well predicted based on
      DOC.

PMID- 16082965
TI  - Identification of hydroxylated polybrominated diphenyl ether metabolites in blood
      plasma from polybrominated diphenyl ether exposed rats.
AB  - Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental contaminants
      due to their use as flame retardants. Similarly to PCBs, the PBDEs are
      metabolized to hydroxylated metabolites (OH-PBDEs) in mammals. In the present
      study equimolar doses of seven environmentally relevant PBDE congeners were given
      intraperitoneally as a mixture to rats, and their blood plasma was analyzed for
      parent compounds and hydroxylated metabolites 1 and 5 days after dosing. Sixteen
      OH-PBDEs and two diOH-PBDEs were detected as PBDE metabolites in the rat plasma,
      a novel finding. Four OH-tetraBDEs were structurally identified by comparison
      (gas chromatography/mass spectrometry) with authentic reference standards. The
      position of the hydroxyl groups was suggested according to the mass spectrometric
      fragmentation patterns of the corresponding PBDE methyl ether derivatives. The OH
      PBDE metabolites were dominated by hydroxyl groups in the meta- and
      parapositions. The results show that OH-PBDE congeners have an ability to be
      retained in rat blood, most likely by a mechanism similar to that of OH-PCBs. The
      results will be useful for determination of the origin of OH-PBDEs present in
      wildlife and in humans, since OH-PBDEs are also common natural products in marine
      environments.

PMID- 16082966
TI  - Receiver operating characteristic analysis for environmental diagnosis. A
      potential application to endocrine disruptor screening: in vitro estrogenicity
      bioassays.
AB  - The realization that certain chemicals are able to disrupt hormonal systems in
      humans and wildlife has challenged the way we assess risk from chemicals and led
      national and international agenciesto devise programsto screen chemicals for
      endocrine-disrupting properties. Chemicals capable of mimicking sex hormones,
      such as estrogens and androgens, have received the most attention, and although
      not yet validated, in vitro techniques to test for such properties are well
      developed. Receiver operating characteristic (ROC) analysis has been successfully
      used in the biomedical and military fields for several decades to assess the
      accuracy of diagnostic tests in terms of both their sensitivity and specificity.
      This approach is applied here to demonstrate its potential to assess how well in
      vitro bioassays can predict estrogenicity in vivo. Despite the limited
      availability of suitable data, the ROC curves obtained indicate that these
      bioassays are effective diagnostic tests. The potential sources of false
      positives and false negatives are identified and potential applications to
      endocrine disruptor screening programs discussed.

PMID- 16082967
TI  - Changes in motor vehicle emissions on diurnal to decadal time scales and effects
      on atmospheric composition.
AB  - Emissions from gasoline and diesel engines vary on time scales including diurnal,
      weekly, and decadal. Temporal patterns differ for these two engine types that are
      used predominantly for passenger travel and goods movement, respectively. Rapid
      growth in diesel fuel use and decreasing NOx emission rates from gasoline engines
      have led to altered emission profiles. During the 1990s, on-road use of diesel
      fuel grew 3 times faster than gasoline. Over the same time period, the NOx
      emission rate from gasoline engines in California was reduced by a factor of
      approximately 2, while the NOx emission rate from diesel engines decreased only
      slightly. Diesel engines therefore grew in both relative and absolute terms as a
      source of NOx, accounting for about half of all on-road NO, emissions as of 2000.
      Diesel truck emissions decrease by 60-80% on weekends. Counterintuitive responses
      to these emission changes are seen in measured concentrations of ozone. In
      contrast, elemental carbon (EC) concentrations decrease on weekends as expected.
      Weekly and diurnal patterns in diesel truck activity contribute to variability in
      the ratio of organic carbon (OC) to EC in primary source emissions, and this
      could be a source of bias in assessments of the importance of secondary organic
      aerosol.

PMID- 16082968
TI  - Modeling salt-dependent proton binding by organic soils with the NICA-Donnan and
      Stockholm humic models.
AB  - Models are available for simulations of proton dissociation and cation binding by
      natural organic matter; two examples are the NICA-Donnan and Stockholm Humic
      (SHM) models. To model proton and metal binding, it is necessary to properly
      account for the ionic strength dependence of proton dissociation. In previous
      applications of the models for soils itwas assumed that the electrostatic
      interactions for solid-phase humic substances were the same as in solution; this
      assumption was recently challenged. Therefore, we reanalyzed previously published
      acid-base titrations of acid-washed Sphagnum peat, and we produced additional
      data sets for two Sphagnum peats and two Spodosol Oe horizons. For the soil
      suspensions, the original NICA-Donnan and SHM models, which were developed for
      dissolved humic substances, underestimated the observed salt dependence
      considerably. When a fixed Donnan volume of 1 L kg(-1) for humic substances in
      the solid phase was used, the NICA-Donnan model fits were much improved. Also for
      SHM, slight changes produced improved model fits. The models also produced
      acceptable simulations of the dissolved Ca, Mg, and Cd concentrations, provided
      that cation selectivitywas introduced. In conclusion, the proposed extensions to
      the NICA-Donnan and SHM models were shown to predict the salt dependence of solid
      phase humic substances more satisfactorily than earlier model versions.

PMID- 16082969
TI  - Detection of herbicide subclasses by an optical multibiosensor based on an array
      of photosystem II mutants.
AB  - Massive use of herbicides in agriculture over the last few decades has become a
      serious environmental problem. The residual concentration of these compounds
      frequently exceeds the maximum admissible concentration in drinking water for
      human consumption and is a real environmental risk for the aquatic ecosystem.
      Herbicides inhibiting photosynthesis via targeting photosystem II function still
      represent the basic means of weed control. A multibiosensor was constructed for
      detecting herbicides using as biosensing elements photosynthetic preparations
      coupled to an optical fluorescence transduction system (Giardi et al. EU patent
      EP1134585, 01830148.1-2204); this paper is about its application in the detection
      of herbicide subclasses in river water. Photosynthetic material was immobilized
      on a silicio septum inside a series of flow cells, close to diodes so as to
      activate photosystem II (PSII) fluorescence. The principle of the detection was
      based on the factthat herbicides selectively modify PSII fluorescence activity.
      The multibiosensor has the original feature of being able to distinguish the
      subclasses of the photosynthetic herbicides by using specific immobilized
      biomediators isolated from mutated organisms. This setup resulted in a reusable,
      portable multibiosensor for the detection of herbicide subclasses with a half
      life of 54 h for spinach thylakoids and limit of detection of 3 x 10(-9) M for
      herbicides present in river water.

PMID- 16082970
TI  - Immobilization of humic acid in nanostructured layer-by-layer films for sensing
      applications.
AB  - Humic acids (HAs), naturally occurring biomacromolecules, were incorporated into
      nanostructured polymeric films using the layer-by-layer (LbL) technique, in which
      HA layers were alternated with layers of poly(allylamine hydrochloride) (PAH).
      Atomic force microscopy (AFM) revealed very smooth films, with mean roughness
      varying from 0.89 to 1.19 nm for films containing 5 and 15 PAH/HA bilayers,
      respectively. The films displayed electroactivity, with the presence of only one
      reduction peak at ca. 0.675 V (vs Ag/AgCl). Such a well-defined electroactivity
      allowed the films to be used as highly sensitive pesticide sensors, with
      detection of pentachlorophenol (PCP) in solutions at concentrations as low as 10(
      9) mol L(-1).

PMID- 16082971
TI  - Online volatile organic compound measurements using a newly developed proton
      transfer ion-trap mass spectrometry instrument during New England Air Quality
      Study--Intercontinental Transport and Chemical Transformation 2004: performance,
      intercomparison, and compound identification.
AB  - We have used a newly developed proton-transfer ion-trap mass spectrometry (PIT
      MS) instrument for online trace gas analysis of volatile organic compounds (VOCs)
      during the 2004 New England Air Quality Study-Intercontinental Transport and
      Chemical Transformation study. The PIT-MS instrument uses proton-transfer
      reactions with H3O+ ions to ionize VOCs, similarto a PTR-MS (proton-transfer
      reaction mass spectrometry) instrument but uses an ion trap mass spectrometer to
      analyze the product ions. The advantages of an ion trap are the improved
      identification of VOCs and a near 100% duty cycle. During the experiment, the PIT
      MS instrument had a detection limit between 0.05 and 0.3 pbbv (S/N = 3 (signal-to
      noise ratio)) for 2-min integration time for most tested VOCs. PIT-MS was used
      for ambient air measurements onboard a research ship and agreed well with a gas
      chromatography mass spectrometer). The comparison included oxygenated VOCs,
      aromatic compounds, and others such as isoprene, monoterpenes, acetonitrile, and
      dimethyl sulfide. Automated collision-induced dissociation measurements were used
      to determine the contributions of acetone and propanal to the measured signal at
      59 amu; both species are detected at this mass and are thus indistinguishable in
      conventional PTR-MS.

PMID- 16082972
TI  - Evaluation of 1047-nm photoacoustic instruments and photoelectric aerosol sensors
      in source-sampling of black carbon aerosol and particle-bound PAHs from gasoline
      and diesel powered vehicles.
AB  - A series of measurements have been performed at Hill Air Force Base to evaluate
      real-time instruments for measurements of black carbon aerosol and particle-bound
      PAHs emitted from spark and ignition compression vehicles. Vehicles were operated
      at idle or fast idle in one set of measurements and were placed under load on a
      dynamometer during the second series. Photoacoustic instruments were developed
      that operated at a wavelength of 1047 nm where gaseous interference is
      negligible, although sensitivity to black carbon is good. Compact, efficient,
      solid-state lasers with direct electronic modulation capabilities are used in
      these instruments. Black carbon measurements are compared with samples collected
      on quartz fiber filters that were evaluated using the thermal optical reflectance
      method. A measure of total particle-bound PAH was provided by photoelectric
      aerosol sensors (PAS) and is evaluated against a sum of PAH mass concentrations
      obtained with a filter-denuder combination. The PAS had to be operated with a
      dilution system held at approximately 150 degrees C for most of the source
      sampling to prevent spurious behavior, thus perhaps compromising detection of
      lighter PAHs. PA and PAS measurements were found to have a high degree of
      correlation, perhaps suggesting that the PAS can respond to the polycyclic nature
      of the black carbon aerosol. The PAS to PA ratio for ambient air in Fresno, CA is
      3.7 times as large in winter than in summer months, suggesting that the PAS
      clearly does respond to compounds other than BC when the instrument is used
      without the heated inlet.

PMID- 16082973
TI  - Simple method for quantifying microbiologically assisted chloramine decay in
      drinking water.
AB  - In a chloraminated drinking water distribution system, monochloramine decays due
      to chemical and microbiological reactions. For modeling and operational control
      purposes, it is necessary to know the relative contribution of each type of
      reaction, but there was no method to quantify these contributions separately. A
      simple method was developed to do so. It compares monochloramine decay rates of
      processed (0.2 microm filtered or microbiologically inhibited by adding 100
      microg of silver/L as silver nitrate) and unprocessed samples under controlled
      temperature conditions. The term microbial decay factor (Fm) was defined and
      derived from this method, to characterize the relative contribution of
      microbiologically assisted monochloramine decay to the total monochloramine decay
      observed in bulk water. Fm is the ratio between microbiologically assisted
      monochloramine decay and chemical decay of a given water sample measured at 20
      degrees C. One possible use of the method is illustrated, where a service
      reservoir's bulk and inlet waters were sampled twice and analyzed for both the
      traditional indicators and the microbial decay factor. The microbial decay factor
      values alone indicated that more microbiologically assisted monochloramine decay
      was occurring in one bulk water than the other. In contrast, traditional
      nitrification indicators failed to show any difference. Further analysis showed
      that the microbial decay factor is more sensitive and that it alone can provide
      an early warning.

PMID- 16082974
TI  - Inclusion of bisphenols by a self-assembled monolayer of thiolated calix[6]arene
      on a gold surface.
AB  - The molecular recognition of various kinds of bisphenols (BPs) by a self
      assembled monolayer (SAM) of thiolated calix[6]arene on a gold electrode was
      examined using cyclic voltammetry (CV). Based on the inhibitory effect of BPs on
      the inclusion of hydroquinone (HQ) as a probe bythe surface-confined
      calix[6]arene, the association constants (Kassoc) of BPs with the immobilized
      calix[6]arene were estimated. The Kassoc values for BPs with the SAM of thiolated
      hexasodium calix[6]arenehexasulfonic acid (thioSCX6) were much smaller than those
      in the free calix[6]arene derivative systems reported previously. The order of
      the Kassoc values for BPs with thioSCX6 was bisphenol A (BPA) > bisphenol S (BPS)
      > bisphenol B (BPB) > bisphenol F (BPF). The Kassoc values for BPA and BPS with
      thioSCX6 were larger than that for BPB, despite the larger hydrophobicity of BPB
      than that of BPA and BPS. This is probably because the inclusion phenomena in
      this system are not simply driven by the hydrophobic interaction, but are
      significantly affected by several steric and structural factors with
      immobilization of the host. Those are (1) a decrease in flexibility of the SCX6
      cavity by the formation of SAM, (2) a decrease in inclusion ability of the SCX6
      by the presence of Au surface just beneath it, and (3) a repulsion of hydrophobic
      guests bythe presence of sulfonate groups at the top of the SAM. Moreover, the
      association phenomena (adsorption and desorption processes) of a bisphenol with
      the SCX6 SAM were examined directly by using localized surface plasmon resonance
      spectroscopy.

PMID- 16082975
TI  - Sol-gel immunosorbents doped with polyclonal antibodies for the selective
      extraction of malathion and triazines from aqueous samples.
AB  - Sol-gel immunosorbents (IS) prepared by encapsulation of polyclonal antibodies in
      silica were packed in cartridges and evaluated for selective immunoaffinity
      extraction (IAE) of malathion and triazines from aqueous samples. Encapsulated
      atrazine antibodies highly cross-reacted with simazine and propazine but did not
      recognize prometon and prometryn. No cross-reactivity of malathion antibodies was
      observed with the closely related metabolites oxomalathion and isomalathion. Mean
      IS binding capacities per milligram of entrapped antibody were 0.33 nmol of
      malathion and 0.47 nmol of atrazine (approximately 100 ng each). This capacity
      remained constant for at least 10 weeks, and the cartridge reusability was
      excellent (>60 IAE runs); also, high preconcentration factors were feasible
      because the breakthrough of analytes from IS cartridges did not occur up to the
      250 mL sample volumes, provided that the capacity was not surpassed. Simple and
      rapid methods for determination of malathion or three triazines in surface water
      were developed using off-line IAE and HPLC-UV. The application to 50 mL dam water
      samples spiked at approximately 1 ng/mL of pesticides resulted in recoveries of
      approximately 90% and RSD < 5% (n=7). LODs for this sample volume (direct
      injection of IS eluates) were in the range of 0.15-0.50 ng/mL. Lower LODs (0.03
      0.1 ng/mL) were achieved by online analysis of whole eluates previously loaded in
      RP precolumns.

PMID- 16082976
TI  - High-temperature liquid water: a viable medium for terephthalic acid synthesis.
AB  - We report new information concerning the effect of oxygen concentration and
      catalyst concentration and identity [MnBr2, CoBr2, ZrBr4, and Mn(OAc)2] on the
      partial oxidation of p-xylene in dense water from 250 to 380 degrees C. Water is
      a more environmentally benign replacementfor the acetic acid solvent used
      commercially. We used a 440 mL Hastelloy batch reactorfor all experiments and
      monitored O2 consumption and product (including COx) formation. Increasing the
      catalyst concentration at 300 degrees C significantly increased terephthalic acid
      yields. MnBr2 was the most active catalyst of those we assessed. Increasing the
      initial O2 concentration beyond a modest excess did not significantly alter the
      terephthalic acid yield, but it increased the CO2 yield. Injecting supplemental
      02 midreaction, however, did cause the terephthalic acid yield to increase. The
      highest terephthalic acid yields (>80%) occurred at 300 degrees C, [p-xylene]0 =
      0.02 M, [O2]0 = 0.10 M, [Br] = 0.014 M, and t = 5-15 min. These yields are the
      highest reported to date from this reaction in high-temperature liquid water.
      Moreover, under these conditions and t=15 min, COx yields were below 2% and
      reaction intermediates were not detected.

PMID- 16082977
TI  - Removal of acetaldehyde vapor with impregnated activated carbons: effects of
      steric structure on impregnant and acidity.
AB  - The acetaldehyde adsorption capacities of activated carbons impregnated with
      various amines were experimentally studied by using fixed beds. It was found that
      the adsorption capacity of impregnated activated carbons is influenced by the
      steric structure of impregnants as well as their acidity. For activated carbons
      impregnated with aromatic amines, ortho and meta substituents on the benzene ring
      hindered the condensation reaction with acetaldehyde. The activated carbon
      impregnated with aminobenzenesulfonic acids differed from that impregnated with
      the other amines in the acetaldehyde adsorption mechanism in that a Doebner
      Miller reaction was involved. Also, aminobenzenesulfonic acids were not only the
      reactant but also the acid catalyst in the removal of acetaldehyde. Since p
      aminobenzenesulfonic acid reacts with acetaldehyde without steric hindrance in
      the Doebner-Miller reaction, it is the most suitable impregnant for the
      chemisorption of acetaldehyde.

PMID- 16082978
TI  - Role of wheat-residue-derived char in the biodegradation of benzonitrile in soil:
      nutritional stimulation versus adsorptive inhibition.
AB  - Previous studies demonstrated that crop-residue-derived chars are effective
      adsorbents for pesticides and substantially reduce their biodegradation in soils.
      In contrast, the nutrients in the chars may stimulate cell growth and hence
      enhance the biodegradation. This work investigated the role of a wheat-residue
      derived char in the nutritional stimulation and adsorptive inhibition of
      biodegradation of benzonitrile in a soil. The biodegradation was measured at 78
      mg/L of benzonitrile, an initial concentration much higher than the half
      saturation constant of the degrading organism (approximately 18 mg/L). The
      degradation was much faster in the extract of char-amended soil (CAS) than in
      those of soil and washed-char-amended soil (WCAS). The degradation was also
      faster in CAS slurry than in slurries of soil and WCAS until approximately 88% of
      benzonitrile degraded in char-containing slurries, where the aqueous-phase
      concentration was approximately 0.25 mg/L. Cell density was higher in extracts
      and slurries in the presence of the char nutrients than in the absence of them.
      Analysis of nutrient elements in extracts, along with measuring degradation in
      soil extract with nutrient supplements and subsequent stepwise multiple
      regression, suggested that the char nutrients stimulated cell growth and
      degradation of benzonitrile, for which P was primarily responsible. Further
      degradation of benzonitrile beyond 88% in the presence of char was slow,
      suggestive of the adsorptive inhibition. The biodegradation of benzonitrile in
      CAS thus occurred through a fast-to-slow process, the former step being due
      primarily to the stimulation by soluble P of char and the latter phase to the
      adsorptive inhibition.

PMID- 16082979
TI  - Behavior of selected pharmaceuticals in subsurface flow constructed wetlands: a
      pilot-scale study.
AB  - Subsurface flow constructed wetlands (SSFs) constitute a wastewater treatment
      alternative to small communities due to the low operational cost, reduced energy
      consumption, and no sewage sludge production. Although much information is
      available about conventional water quality parameters in SSF constructed
      wetlands, few data are available regarding specific contaminants. In this paper,
      we focus on the behavior of three widely used pharmaceuticals (clofibric acid,
      ibuprofen, and carbamazepine) in two pilot SSF constructed wetlands planted with
      Phragmites australis and characterized by different water depths (i.e., 0.3 and
      0.5 m). These SSFs partially treat the urban wastewater from a housing
      development (ca. 200 inhabitants). The three pharmaceuticals and bromide were
      continuously injected into the two SSFs during a period of 150-200 h, and the
      effluent concentration was simultaneously measured as 6 h composite samples.
      Their removal efficiency was calculated from the injected concentration, and the
      hydraulic parameters were evaluated and compared to bromide as tracer. In this
      regard, the behavior of clofibric acid was similar to that of bromide, and no
      sorption into the gravel bed occurred. On the other hand, carbamazepine showed a
      higher sorption than bromide and clofibric acid, which is attributable to its
      interaction on the gravel bed. Accordingly, the use of clofibric acid as a
      hydraulic tracer is proposed, taking into account its low residence time.
      Ibuprofen removal was 81% in the shallow SSF and 48% in the deep one. Differences
      in removal efficiency could be explained by the less anaerobic environment of the
      shallow wetland.

PMID- 16082980
TI  - Selective removal of 226Ra2+ from gas-field-produced waters.
AB  - The 226Ra2+ selectivity of both the self-assembled (iso)-guanosine-based systems
      and ionizable thiacalix[4]crown dicarboxylic acids was determined in gas-field
      produced water and a metal ion-containing model solution (simulant). Seven gas
      field-produced water samples have been analyzed. From a sample (K5D) with average
      metal ion concentrations ([metal(tot)] = 0.14 M), thiacalix[4]crown-5
      dicarboxylic acid (10(-4) M) extracts 60% of the 226Ra2+ content. Extractions
      performed with the model solution ((M)K5D) indicate that in K5D there is
      significant competition in 226Ra2+ extraction due to the organic constituents of
      K5D, in particular with self-assembled extractants guanosine and isoguanosine.
      Nevertheless, all four extractants extract 226Ra2+ both from the produced water
      K5D and the model solution (M)K5D, even with a 100-fold excess of [metal(tot)] to
      [extractant]. The extracted 226Ra2+ cations could effectively be stripped from
      the extractants bywashing with pH 2 water. The results obtained with the
      extractants used, especially thiacalix[4]crown-5 dicarboxylic acid 3, clearly
      demonstrate the way to selectively remove Ra2+ from gas-field-produced waters.

PMID- 16082981
TI  - Biofiltration for mitigation of methane emission from animal husbandry.
AB  - Removal of methane from exhaust air of animal houses and manure storage has a
      large potential for the reduction of greenhouse gas emissions from animal
      husbandry. The aim of this study was to design a biofilter for methane removal at
      a full-scale livestock production facility. Air from the headspace of a covered 6
      m3 liquid manure storage (air flow: 0.75-8.5 m3 m(-3) h(-1); CH4: 500-5500 mg m(
      3)) was treated in an experimental biofilter (160 L). The filterbed, a mixture of
      compost and perlite in a 40:60 (v/v) ratio, was inoculated with activated sludge
      that had shown a good methane oxidation rate as compared to pure cultures in
      preceding laboratory tests. Methane removal up to 85% could be achieved in the
      experimental biofilter. The methane removal (g m(-3) h(-1)) appeared to be
      proportional to the concentration (g m(-3)) with k = 2.5 h(-1). Relatively low
      methane concentrations and high air flows, as reported for the exhaust air of
      animal houses, would require very large biofilter sizes. Extrapolation of the
      results showed that treatment of air from a 1000 m3 liquid manure storage with a
      methane concentration of 22 g m(-3) would require a 20 m3 biofilter for a desired
      emission reduction of 50%. The costs for such a biofilter are USD 26 per t of CO2
      equiv reduction.

PMID- 16082982
TI  - Pyrolysis study of halogen-containing aromatics reflecting reactions with
      polypropylene in a posttreatment decontamination process.
AB  - Halogen-containing aromatics, mainly bromine-containing phenols, are harmful
      compounds contaminating pyrolysis oil from electronic boards containing
      halogenated flame retardants. In addition,theirformation increases the potential
      for evolution of polybrominated dibenzo-p-dioxins (PBDDs) and dibenzofurans
      (PBDFs) at relatively low temperature (up to 500 degrees C). As a model compound,
      2,4-dibromophenol (DBP) was pyrolyzed at 290-450 degrees C. While its pyrolysis
      in a nitrogen flow reactor or in encapsulated ampules yields bromine-containing
      phenols, phenoxyphenols, PBDDs, and PBDFs, pyrolysis of DBP in a hydrogen
      donating medium of polypropylene (PP) at 290-350 degrees C mainly results in the
      formation of phenol and HBr, indicating the occurrence of a facile
      hydrodebromination of DBP. The hydrodebromination efficiency depends on
      temperature, pressure, and the ratio of the initial components. This thermal
      behavior of DBP is compared to that of 2,4-dichlorophenol and decabromodiphenyl
      ether. A treatment of halogen-containing aromatics with PP offers a new
      perspective on the development of low-environmental-impact disposal processes for
      electronic scrap.

PMID- 16082983
TI  - Characterization of phosphate accumulation in Lolium multiflorum for remediation
      of phosphorus-enriched soils.
AB  - Deterioration in water quality caused by the movement of excessive soil P has
      created a condition necessary for the development of a sustainable P remediation
      technology. In this investigation, the phytoremediation potential of Gulf and
      Marshall ryegrass (Lolium multiflorum) grown in a greenhouse was determined under
      varying conditions of soil P concentration, pH, and temperature. Both genotypes
      demonstrated P accumulations > or =1% shoot dry weight depending on soil P
      concentrations (0-10 g of P/kg of soil), with higher shoot P in Gulf than
      Marshall ryegrass. An increase in plant biomass was proportional to the
      increasing concentrations of P up to a level of 10 g of P/kg of soil. The effect
      of soil pH on plant uptake of P was noticeable with a significant rise in shoot P
      in acidic soil (pH 5.6) as compared to soil with pH 7.8. Significant differences
      were observed in the biomass productivity and shoot P accumulation at varying
      temperatures in both grass types. The patterns of acid phosphomonoesterase and
      phytase activities in plant roots were interesting, activities being 2-fold
      higher in alkaline soil than acidic soil in both genotypes. The effect of P
      supply on the enzyme activity was also distinct, as plants growing in a high P
      concentration showed higher activity (nearly 30%) than those growing under P
      deficiency conditions (with no addition of P). These results indicate that Gulf
      and Marshall ryegrass can accumulate high P under optimal conditions and thus
      reduce soil P concentrations in successive cropping.

PMID- 16082984
TI  - Arsenic leachability in water treatment adsorbents.
AB  - Arsenic leachability in water treatment adsorbents was studied using batch
      leaching tests, surface complexation modeling and extended X-ray absorption fine
      structure (EXAFS) spectroscopy. Spent adsorbents were collected from five pilot
      scale filters that were tested for removal of arsenic from groundwater in
      Southern New Jersey. The spent media included granular ferric hydroxide (GFH),
      granular ferric oxide, titanium dioxide, activated alumina, and modified
      activated alumina. The As leachability determined with the Toxicity
      Characteristic Leaching Procedure (TCLP, 0.1 M acetate solution) was below 180
      microg L(-1) for all spent media. The leachate As concentration in the California
      Waste Extraction Test (0.2 M citrate solution) was more than 10 times higher than
      that in the TCLP and reached as high as 6650 microg L(-1) in the spent GFH
      sample. The EXAFS results indicate that As forms inner-sphere bidentate binuclear
      surface complexes on all five adsorbent surfaces. The As adsorption/desorption
      behaviors in each media were described with the charge distribution multisite
      complexation model. This study improved the understanding of As bonding
      structures on adsorptive media surfaces and As leaching behavior for different
      adsorbents.

PMID- 16082985
TI  - Power generation in fed-batch microbial fuel cells as a function of ionic
      strength, temperature, and reactor configuration.
AB  - Power density, electrode potential, coulombic efficiency, and energy recovery in
      single-chamber microbial fuel cells (MFCs) were examined as a function of
      solution ionic strength, electrode spacing and composition, and temperature.
      Increasing the solution ionic strength from 100 to 400 mM by adding NaCl
      increased power output from 720 to 1330 mW/m2. Power generation was also
      increased from 720 to 1210 mW/m2 by decreasing the distance between the anode and
      cathode from 4to 2 cm. The power increases due to ionic strength and electrode
      spacing resulted from a decrease in the internal resistance. Power output was
      also increased by 68% by replacing the cathode (purchased from a manufacturer)
      with our own carbon cloth cathode containing the same Pt loading. The performance
      of conventional anaerobic treatment processes, such as anaerobic digestion, are
      adversely affected by temperatures below 30 degrees C. However, decreasing the
      temperature from 32 to 20 degrees C reduced power output by only 9%, primarily as
      a result of the reduction of the cathode potential. Coulombic efficiencies and
      overall energy recovery varied as a function of operating conditions, but were a
      maximum of 61.4 and 15.1% (operating conditions of 32 degrees C, carbon paper
      cathode, and the solution amended with 300 mM NaCl). These results, which
      demonstrate that power densities can be increased to over 1 W/m2 by changing the
      operating conditions or electrode spacing, should lead to further improvements in
      power generation and energy recovery in single-chamber, air-cathode MFCs.

PMID- 16082986
TI  - Comment on "Correlation equation for predicting single-collector efficiency in
      physicochemical filtration in saturated porous media".

PMID- 16082987
TI  - Comment on "Perchlorate and iodide in dairy and breast milk".

PMID- 16082988
TI  - Comment on "Reliability of a commercial kit to test groundwater for arsenic in
      Bangladesh".

PMID- 16082989
TI  - Appropriate and timely empirical antimicrobial treatment of icu infections--a
      role for carbapenems.
AB  - Treatment of serious nosocomial infections in the intensive care unit requires
      swift, effective, well-tolerated and appropriate therapy from the outset. The
      consequences of inappropriate treatment, i.e. the use of antibiotics that are
      ineffective against the causative pathogen(s) or delayed therapy, are numerous
      and impact negatively upon both the patient and the ever-dwindling healthcare
      resources in many hospitals. Although antibiotics have revolutionised the
      treatment of infections, their inappropriate and untimely use within the
      intensive care setting has led to the emergence and spread of antibiotic
      resistant bacteria worldwide. Consequently, to ensure successful patient outcomes
      (reduce morbidity and mortality), it is important that any antibiotic treatment
      employed is right first time. Treatment of serious infections in the intensive
      care unit requires an empirical stratagem providing broad-spectrum coverage to a
      wide range of suspected or difficult-to-treat pathogens such as Pseudomonas
      aeruginosa. However, to prevent the errors of the past, this needs to be tailored
      as soon as the pathogen has been identified and resistance patterns are known.
      The carbapenems are potent parenteral antibiotics, with an ultra-broad spectrum
      of activity that encompasses multi-drug resistant and difficult-to-treat Gram
      negative bacteria. Clinical trial data supports the clinical effectiveness of
      these agents in patients with difficult to treat pathogens.

PMID- 16082990
TI  - An outbreak of nosocomial hepatitis B virus infection in a nursing home for the
      elderly in Antwerp (Belgium).
AB  - After notification of a case of fulminant hepatitis B virus (HBV) infection in a
      83-year-old female resident of a nursing home to the Flemish Health Inspectorate,
      a seroepidemiological study and a retrospective cohort study were conducted among
      the 94 residents and 47 nursing staff to assess the extent of HBV transmission
      and to identify risk factors. Susceptible residents were vaccinated against HBV
      and their serological response to hepatitis B vaccination determined. From
      December 2002 to April 2003, five residents with acute hepatitis B infection were
      identified with an attack rate of 5.5% and a case fatality rate of 40%. Three
      other residents were identified as HBV surface antigen and e-antigen positive
      carrier. None of the nursing staff tested positive for acute HBV infection or HBV
      carriage. Diabetic patients who were exposed to a shared finger-stick device for
      blood sampling were 10.7 times more likely to contract an acute HBV infection (RR
      10.7; 95% CI 1.3-91.3). Other potential risk factors were undergoing podiatric
      care and being exposed to the shared razor blade of the hairdresser. The
      transmission of the infection could be controlled by restricting the use of
      finger-stick capillary sampling devices to individual patients, assigning
      separate glucometers to individual patients and, implementation of standard
      infection-control recommendations like wearing gloves and performing hand hygiene
      by the nursing staff, assigning separate podiatric sets to individual patients.
      HBV vaccination of the residents with three doses of HBV vaccine has not induced
      a sufficient degree of protection. The outbreak stresses the need for appropriate
      and generally applied standard procedures in nursing homes to prevent bloodborne
      pathogens.

PMID- 16082991
TI  - STI surveillance by a sentinel network of physicians in Belgium.
AB  - The STI sentinel surveillance network by physicians in Belgium started in 2000.
      During 4 months a year, from October until January, STI patients were registered
      using a standardized protocol. The main goal is to determine STI incidence trends
      by comparing the results of the analyses using the data of the physicians that
      registered in all registration periods (Oct. 2000-Jan. 2001; Oct. 2001-Jan. 2002;
      Oct. 2002-Jan. 2003; Oct. 2003-Jan. 2004). Between the registration periods 2000
      2001 and 2002-2003, there was a significant increase in the number of syphilis
      diagnoses (p<0.01), largely attributable to infections in men who have sex with
      men (MSM). A high proportion of MSM with syphilis were HIV positive. 83% of HIV
      positive MSM were already aware of their HIV positive status. The proportion of
      STI patients with HIV co-infection increased significantly throughout the
      different periods (from 7.4% in 2000-2001 to 18.1% in 2003-2004; p<0.01). These
      findings emphasize the importance of the proposal of a HIV test in a STI patient
      and call for intensification of prevention measures, particularly in MSM and
      people living with HIV.

PMID- 16082992
TI  - Evaluation of the Stratus CS fluorometer for the determination of plasma
      myoglobin.
AB  - Circulating myoglobin is recognized as an early and sensitive marker of acute
      coronary diseases. Long turnaround time of myoglobin assays jeopardize their
      clinical utility. We evaluated the analytical performance of the Stratus CS
      fluorometric enzyme immunoassay based on dendrimer technology, and claimed to
      achieve a fast and reliable determination of plasma myoglobin concentrations.
      Precision complied with the recommended analytical performance criteria. Method
      comparison and recovery experiments indicated, that despite good between-method
      correlations, the Stratus CS method overestimated myoglobin concentrations in
      comparison with values obtained on Cobas Integra 400 and BN A. However, since the
      manufacturers' cut-off for elevated plasma myoglobin levels was higher for
      Stratus CS than for other techniques, few discrepant results were observed
      between methods. Elevated levels of hemoglobin, triglycerides and rheumatoid
      factors did not interfere in the Stratus CS method but hyperbilirubinemia caused
      a positive difference.

PMID- 16082993
TI  - The treat-to-target paradigm: a cross-sectional survey of current therapies and
      achieved metabolic control in 800 type 2 diabetic patients.
AB  - The aim of this cross-sectional study is to analyse the current treatment schemes
      as well as the quality of control (metabolic; blood pressure) in a cohort of 800
      type 2 diabetic patients recruited in a University Center and not by generalist
      practionners, in scope with current international recommendations. Insulin
      therapy was administered, alone or combined with oral antihyperglycaemic drugs,
      to 48% of subjects. HbA1c was 7.7% (6.7-8.7 (median; percentiles 25-75)).
      Antidyslipidaemic drugs were used in 45% of individuals. However, only 27% of the
      cohort had LDL levels lower than 100 mg/dl while 58% of males and 48% of females
      attained HDL targets. Systolic and diastolic blood pressure levels were 144 +/-
      21 and 81 +/- 12 mmHg (mean +/- SD), despite one or more antihypertensive
      agent(s) prescribed to 68% of subjects. In conclusion, in a Belgian adult type 2
      diabetic population attending a tertiary centre for follow-up, overall metabolic
      and blood pressure controls remain unsatisfactory according to targets defined by
      international guidelines. This audit makes a multi-faceted intervention aimed at
      intensifying current therapies all the more necessary.

PMID- 16082994
TI  - The podocyte: from bench to bedside.
AB  - The understanding of the molecular structure of the podocyte has increased
      considerabely in recent 5 years by genetic research in inherited
      glomerulopathies. Injury to the podocyte often leads to a reorganisation of the
      slit diaphragm and to foot process effacement, which can be noted in all forms of
      the nephrotic syndrome. Since the recent progress in our understanding of the
      molecular biology of the podocyte, it has become obvious that the podocyte is
      crucial in the pathogenesis of not only genetic but also of many acquired
      glomerulopathies such as focal segmental glomerulosclerosis, membranous
      glomerulopathy and diabetic nephropathy. In this review we provide a summary of
      the recent physiological and molecular insights into the podocyte and of its
      significance in different glomerulopathies.

PMID- 16082995
TI  - Primary amyloidosis (AL) as a cause of nephrotic syndrome.
AB  - AL amyloidosis is a rare systemic disease resulting from tissue accumulation of
      amyloid fibrils derived from monoclonal immunoglobulin light chains. It can
      disrupt the tissue architecture and consequently cause organ dysfunction. The
      prognosis is poor with a median survival of 13 months in untreated patients. By
      illustrating the case of a patient whose AL amyloidosis was detected after
      presenting a nephrotic syndrome, the characteristics of the disease are reviewed
      as well as diagnostic criteria and current available therapeutics.

PMID- 16082996
TI  - Choking, sore throat with referred otalgia and dysphagia in a patient with
      diffuse idiopathic skeletal hyperostosis (DISH).
AB  - A patient with a progressively increasing immobilisation of the cervical spine,
      severe impaired swallowing (choking), sore throat with referred right-sided
      otalgia, mild voice disorder and dysphagia due to extrinsic bone compression of
      the posterior hypopharyngeal wall and oesophagus is presented. Radiographic
      investigation demonstrated the underlying condition to be a diffuse idiopathic
      skeletal hyperostosis with prominent and bumpy alteration of the anterior
      longitudinal ligament impinging the hypopharynx. Via an anterolateral approach
      towards the cervical spine the anterior irregular part of the ossification was
      removed and the surface of the spine flattened. The postoperative evolution was
      uneventful.

PMID- 16082997
TI  - Management of therapy-resistant systemic lupus erythematosus with rituximab:
      report of a case and review of the literature.
AB  - Therapy of systemic lupus erythematosus (SLE) with major organ involvement
      consists of aggressive immunosuppression with glucocorticoids and cytotoxic
      agents. When remission is achieved, maintenance therapy is begun to reduce the
      risk of relapse while minimizing toxicity. Remission with standard therapy is,
      however, not always achieved. We discribe a women with SLE and microangiopathic
      haemolytic anaemia and thrombocytopenia, pneumonitis and nephritis refractory to
      high-dose steroids, pulse cyclophosphamide, plasmapheresis and intravenous
      immunoglobulins. The anti-CD20 monoclonal antibody rituximab was administered,
      resulting in major clinical and biochemical improvement. Therapy-resistant SLE
      generally has an ominous prognosis. A few anecdotal reports and small open
      studies describe beneficial effects of rituximab in these cases. Rituximab may be
      a promising new approach to improve the dismal outcome of therapy-resistant SLE.

PMID- 16082998
TI  - Time is up!

PMID- 16082999
TI  - [On the 100th birthday of Andrei Nikolaevich Belozerskii].

PMID- 16083000
TI  - [A.N. Belozerskii and establishment of molecular biology].

PMID- 16083001
TI  - [Institute named for A.N. Belozerskii: experience in organizing Russian
      University Science].

PMID- 16083002
TI  - [A. N. Belozerskii and his institute].

PMID- 16083003
TI  - [My friend and wise chef].

PMID- 16083004
TI  - [RNA world and its evolution].
AB  - The early idea of A. N. Belozersky on the precedence of RNA in the origin of life
      on Earth is developed. Basing on the present knowledge of functional omnipotence
      of RNA, the author considers three novel mechanisms that could play a critical
      role in the origin and evolution of the ancient RNA world: (1) the reaction of
      spontaneous transesterification of polyribonucleotides in aqueous media,
      discovered by A.B. Chetverin, which could result in elongation of primary short
      oligoribonucleotides and generation of sequence variants for subsequent
      selection; (2) compartmentation of functional RNA ensembles in the form of mixed
      molecular colonies on moist solid surfaces, in the absence of membranes and any
      other coats; (3) systematic exponential enrichment of RNA population in
      functionally "the best" molecules by means of alternately dissolving the colonies
      upon flooding and forming new ones upon drying a pool ("primordial natural
      SELEX").

PMID- 16083005
TI  - [Methylation of adenine residues in DNA of eukaryotes].
AB  - Like in bacteria, DNA in these organisms is subjected to enzymatic modification
      (methylation) both at adenine and cytosine residues. There is an indirect
      evidence that adenine DNA methylation takes place also in animals. In plants m6A
      was detected in total, mitochondrial and nuclear DNAs; in plants one and the same
      gene (DRM2) can be methylated both at adenine and cytosine residues. ORF
      homologous to bacterial adenine DNA-methyltransferases are present in nuclear DNA
      of protozoa, yeasts, insects, nematodes, higher plants, vertebrates and other
      eukaryotes. Thus, adenine DNA-methyltransferases can be found in the various
      evolutionary distant eukaryotes. First N6-adenine DNA-methyltransferase
      (wadmtase) of higher eukaryotes was isolated from vacuolar fraction of vesicles
      obtained from aging wheat coleoptiles; in the presence of S-adenosyl-L-methionine
      this Mg2+ -, Ca2+ -dependent enzyme de novo methylates first adenine residue in
      TGATCA sequence in single- and double-stranded DNA but it prefers single-stranded
      DNA structures. Adenine DNA methylation in eukaryotes seems to be involved in
      regulation of both gene expression and DNA replication including replication of
      mitochondrial DNA. It can control persistence of foreign DNA in a cell and seems
      to be an element of R-M system in plants. Thus, in eukaryotic cell there are, at
      least, two different systems of the enzymatic DNA methylations (adenine and
      cytosine ones) and a special type of regulation of gene functioning based on the
      combinatory hierarchy of these interdependent genome modifications.

PMID- 16083006
TI  - [Peculiarities of metabolism and functions of high-molecular inorganic
      polyphosphates in yeasts as representatives of lower eukaryotes].
AB  - The review presents the recent data demonstrating the important role high
      molecular inorganic polyphosphates in regulatory processes in a yeast cell. It
      has been shown that polyphosphates are localized in different cell compartments,
      where they are metabolized by a special set of enzymes. The review presents the
      evidence in favor of the concept of multiple functions of these biopolymers in a
      cell, as well as the data on the pleiotropic effects of mutations in the genes
      encoding the enzymes of polyphosphate metabolism.

PMID- 16083007
TI  - [Genosystematics: from E. Chargaff and A. N. Belozersky up to date].
AB  - A review of history of genosystematics (macromolecular systematics) from E.
      Chargaff and A. N. Belozersky up to date. The role of A.N. Belozersky and his
      collaborators in the development of this new branch of systematics is analyzed.
      Genosystematics was the source of valuable information clarifying some aspects of
      biological evolution. Its methods were successfully employed in microorganisms-
      (e.g., discovery of archaebacteria) and in eucaryote systematics (origin of
      plastids, falcification of "molecular clock" hypothesis, substantial changes in
      higher plants phylogenetics, etc.). However, attempts to employ some fragmentary
      and unreliable data obtained by genosystematics for modifying the existing
      phylogenetic schemes and systems of organisms failed. Nowadays genosystematics is
      like a newborn child suffering from children's diseases well-known to "classical"
      systematics. It is rather far from final conclusions describing the evolution of
      genotypes. Some of its recent achievments, e.g., elaboration of the concept of
      PhyloCode, allow to believe that this science is able to suggest revolutionary
      changes in Linnean systematics.

PMID- 16083008
TI  - [Phylogeny of protostome moulting animals (Ecdysozoa) inferred from 18 and 28S
      rRNA gene sequences].
AB  - Reliability of reconstruction of phylogenetic relationships within a group of
      protostome moulting animals was evaluated by means of comparison of 18 and 28S
      rRNA gene sequences sets both taken separately and combined. Reliability of
      reconstructions was evaluated by values of the bootstrap support of major
      phylogenetic tree nodes and by degree of congruence of phylogenetic trees
      inferred by various methods. By both criteria, phylogenetic trees reconstructed
      from the combined 18 and 28S rRNA gene sequences were better than those inferred
      from 18 and 28S sequences taken separately. Results obtained are consistent with
      phylogenetic hypothesis separating protostome animals into two major clades,
      moulting Ecdysozoa (Priapulida + Kinorhyncha, Nematoda + Nematomorpha,
      Onychophora + Tardigrada, Myriapoda + Chelicerata, Crustacea + Hexapoda) and
      unmoulting Lophotrochozoa (Plathelminthes, Nemertini, Annelida, Mollusca,
      Echiura, Sipuncula). Clade Cephalorhyncha does not include nematomorphs
      (Nematomorpha). Conclusion was taken that it is necessary to use combined 18 and
      28S data in phylogenetic studies.

PMID- 16083009
TI  - [Photoreceptor apparatus of a fungus Neurospora crassa].
AB  - Light governs living functions of ascomycete fungus Neurospora crassa by
      controlling expression of the genes responsible for differentiation of
      reproductive structures, synthesis of secondary metabolites and the circadian
      oscillator activity. Illumination also influences electrogenic processes in cell
      membrane and the activity and molecular organization of some enzymes. The major
      but, probably, not the sole photoreceptor pigment in Neurospora cells is WCC, a
      heterodimeric complex formed by PAS-domain-containing polypeptides WC-1 and WC-2,
      which are the products of genes white collar-1 and white collar-2. Mutation of
      any of these genes arrests most of the organism's responses to light. The
      photoreceptor belongs to a recently discovered vast group of non-homologous light
      sensitive proteins, whose molecules bind flavin coenzymes as the photosensor
      chromophores. The photosignal transduction is started by excitation and
      photochemical activity of excited FAD molecule non-covalently bound by LOV-domain
      (a specialized version of PAS-domain) in WC-1 protein. The presence in both WC-1-
      and WC-2-proteins of "zinc fingers" (the GATA recognizing sequences) suggested
      that these motives might act as transcription factors. The critical analysis of
      photoinduction mechanism has shown, however, that promoters of light-sensitive
      genes do not contain a common cis-acting element, what makes to look for
      alternative mechanisms underlying photoregulated gene activity.

PMID- 16083010
TI  - [Variable mechanisms of RNA-recombination].
AB  - Recombination is widespread among RNA viruses but underlying mechanisms remain
      poorly understood. Until recently, replicative template switching was considered
      the only possible mechanism of RNA recombination but new evidence suggests that
      other variants of replicative mechanisms may also exist. In addition,
      nonreplicative recombination (i.e., joining of preexisting molecules) of genomes
      of RNA viruses is possible. Recombination is an efficient tool contributing to
      both variability and stability of the viral RNA genomes. Nonreplicative joining
      of RNA pieces in the form of trans-splicing is an important physiological
      mechanism in at least certain organisms. It is conceivable that RNA-recombination
      has contributed, and perhaps is still contributing, to the evolution of DNA
      genomes.

PMID- 16083011
TI  - [The spatial organization of DNA in the nucleus may determine positions of
      recombination hot-spots].
AB  - We suggest a hypothesis postulating that sites of DNA loop anchorage to the
      nuclear matrix harbor "hot spots" of illegitimate recombination which is mediated
      or triggered by topoisomerase II of the nuclear matrix. Recombination between DNA
      loop anchorage sites may result in deletion and/or repositioning of DNA loops and
      loop oligomers. This hypothesis is corroborated by our own results and published
      results of other research groups.

PMID- 16083012
TI  - [Mammalian 87 small nucleolar RNA and its host gene].
AB  - The vast majority of C/D box small nucleolar RNAs (snoRNAs) direct site-specific
      methylation of ribose in rRNA. New mammalian snoRNA U87 belongs to the C/D family
      and is involved in ribose methylation of guanylic acid residue (position 3468) in
      28S rRNA. A host gene harboring the U87 snoRNA gene in its intron was described
      for rodents and humans. In humans it has three neighbouring transcription start
      sites whereas in rat there are many scattered start sites. The transcript of this
      gene possesses some characteristic features of an mRNA (splicing, polyadenylation
      and cytoplasmic localization) but lacks long open reading frames and the degree
      of its conservation is much less than that of other host gene mRNAs. Such low
      conservation is discussed in the context of functional significance of exonic
      sequences of the gene.

PMID- 16083013
TI  - [Molecular mechanisms of germ cell line determination in animals].
AB  - In the present work, principles of formation of germ line cells are reviewed.
      Germ line cells separate themselves from the rest of the embryo at the early
      stages of embryogenesis. In certain animal groups, formation of precursors of
      germ cells occurs by induction by surrounding cells. However, for most animal
      taxons, formation of primordial germ cells (PGCs) is determined by inheritance of
      certain maternal determinants--the so-called germ plasm. It is formed by
      mitochondria, electron-dense granules with the complex structure, and maternal
      RNAs and proteins necessary for formation of germ line. In Xenopus, the source of
      material for germ plasm is a mitochondrial cloud, which also specifically binds
      and transports to the vegetal pole maternal RNAs important for PGC formation. Cis
      elements determining the transport of these RNAs are usually located in the 3'
      untranslated region of RNA, and their function is mediated by binding of trans
      acting protein factors. In addition to a specific localization of certain
      macromolecules in germ plasm, special status of germ line cells is provided by
      degradation of RNA and protein components of germ plasm in somatic cells,
      silencing of transcription in PGCs until advanced stages of embryogenesis, and
      specific regulation of RNA translation in somatic and germ cells. In this review,
      we also briefly discuss results obtained by authors regarding the properties of a
      novel component of Xenopus germ plasm, namely maternal RNA germes, and encoded
      protein.

PMID- 16083014
TI  - [Assays on comparing the local concentration of HU protein in the different
      regions of Escherichia coli genomic DNA].
AB  - HU, a nonspecific histone-like DNA binding protein is a major component of the
      bacterial nucleoid. HU is referred to as an accessory factor for complex protein
      DNA assembly and as a protein involved in DNA compaction. In this study we
      investigated in vivo HU binding along the different regions of E. coli genome.
      For this purpose we used ChIP--in vivo formaldehyde crosslinking and
      immunoprecipitation of protein-DNA complexes with antiHU-antibodies. This
      technique allows to compare the local concentration of HU protein in the
      different regions of E. coli genomic DNA. In this study we analysed the HU-DNA
      crosslinking both in exponentially growing and stationary phase of bacteria in
      the following regions of E. coli genome: oriC region, promoter and structural
      regions of hupA and hupB genes coding two different subunits of HU, and
      structural parts of dps and glgS genes which are active only in stationary phase.
      Our results indicate that in exponentially growing E. coli cells the local
      concentration of HU protein is uniform for all analysed regions of genome and
      does not depend on their transcriptional status. The twofold increase of local
      concentration of HU protein was also shown for all analysed genome regions in the
      stationary phase cells.

PMID- 16083015
TI  - [NotI-STS markers for human chromosome 3 are gene markers].
AB  - Ninety four NotI-STS markers to seventy two individual NotI clones were developed
      basing on DNA nucleotide sequences from NotI-"jumping" and "linking" NotI
      libraries of human chromosome 3. The localization of NotI-STS markers and their
      ordering on chromosome was established by combined data of RH-mapping (our data),
      contig-mapping, cytogenetic mapping and in silico mapping. Performed comparison
      of NotI-STS DNAs with human genome sequences revealed two gaps in the regions,
      3p21.33 (marker NLI-256) and 3p21.31 (NL3-005), and segmental duplication.
      Identical DNA fragments are localized in the regions 12q and 3p22-21.33 (marker
      NL3-007). In the region 3q28-q29 (marker NLM-084) a fragment was detected with
      its identical copies present also on chromosomes 1, 2, 15 and 19. For 69 NotI
      STSs, significant homologies with nucleotide sequences of 70 genes and two cDNAs
      were detected taking in consideration homologies to NotI-STS 5'- and 3'-terminal
      sequences. Association of NotI-STSs with genes is confirmed by high correlation
      of gene density distribution with the density of NotI-STS markers on the map of
      human chromosome 3. Obtained data evidence possibility of NotI-STS marker
      application as gene markers and allow considering constructed NotI-map as gene
      map of human chromosome 3.

PMID- 16083017
TI  - [Interaction of the molecular motors].
AB  - A review addresses the up-to-date evidence on the regulation of the organelle
      transport along microtubules in a very specific aspect of the interaction of the
      molecular motors of the opposite directions.

PMID- 16083016
TI  - [Protease inhibitors: use to increase plant tolerance to insects and pathogens].
AB  - The review deals with analysis of the possibility of the use of genes of
      inhibitors of proteolytic enzymes of plants to increase plant tolerance to insect
      pests and phytopathogens. The idea of using protease inhibitors for plant defense
      is strongly supported, first, by their wide distribution in plant tissues and
      high activity towards various proteolytic enzymes of insects, bacteria and fungi.
      The results obtained for the last years indicate that the genetic engineering
      approach is perspective for solving of this kind of problems. The main losses and
      advantages of the discussed approach are also considered. The described approach
      for increase of plant tolerance to insects and pathogens has few advantages as
      compared to traditional ones and belongs to ecologically pure technologies.

PMID- 16083018
TI  - Adequacy of haemodialysis.
AB  - Inadequate dialysis is easier to define and recognise than adequate dialysis.
      Defining inadequate dialysis is thus the first step and allows the establishment
      of a minimum acceptable dose of dialysis that is compatible with short-term well
      being and the absence of uraemic symptoms. An optimal dialysis dose is harder to
      define but should include such factors as the patient's clinical symptomology,
      nutritional status and achievement of a fully active, rehabilitated life.

PMID- 16083019
TI  - Staphylococcal infections in PD: monitoring, screening and prevention.
AB  - Peritonitis and catheter infections remain a major complication of peritoneal
      dialysis, accounting for much of the morbidity associated with the technique. The
      most common source of infection is contamination with predominantly Gram positive
      skin flora, Staphylococcus (S) epidermidis and S. aureus. The aims of this study
      were, (a) to determine the incidence of S. aureus and S. epidermidis infections
      in the unit, (b) to examine whether treatment of S. aureus carriers may reduce
      the incidence of exit site infection and (c) to examine whether improving patient
      education may reduce S. epidermidis peritonitis rate.

PMID- 16083020
TI  - Dialysate leakage in CAPD patients.
AB  - Dialysate leakage may occur through the anterior abdominal wall, the genital
      organs or the pleural cavity during the early or late stages of dialysis in
      patients who are on continuous ambulatory peritoneal dialysis (CAPD). This
      dialysate leakage can reach such an extent that CAPD treatment may need to be
      halted. Dialysate leakage through the subcutaneous anterior abdominal wall can be
      caused by a deficiency in the abdominal muscles. In this study, 3 patients on
      CAPD who had a dialysate leak through the subcutaneous anterior abdominal wall
      were followed. An exercise programme was offered to strengthen abdominal muscles.
      CAPD continued but volumes were reduced by 6-25%. Exercise programmes for
      abdominal muscles may be useful for the prevention of leakage through the
      subcutaneous anterior abdominal wall, without having to interrupt CAPD treatment.

PMID- 16083021
TI  - Discrepancies in performing target weight assessments in haemodialysis patients.
AB  - Roberts and White (1) state that the main reason for hospitalisation of dialysis
      patients is due to 'fluid Volume excess'. Fluid/target weight assessments should
      routinely be carried out for chronic haemodialysis patients prior to each
      treatment by experienced renal nurses, but Welsh (2) states that the assessment
      of the patient and clinical skills may be underused because of poor staffing
      levels. Using a qualitative design study based on a group of experienced renal
      nurses, the author sought to determine which clinical signs and symptoms were
      assessed, how often they were carried out and what similarities were
      demonstrated. Elements such as the patient's blood pressure, evidence of
      peripheral oedema and dyspnoea were used as benchmarks for good practice, based
      on literature and the author's extensive experience. The author also believed
      that the standard fluid assessment could be improved by expanding the nurse's
      role to incorporate chest auscultation. Results demonstrated that a variety of
      reasons determined whether such assessments were carried out, and that there was
      wide variation as to what nurses considered essential in performing the
      assessment.

PMID- 16083022
TI  - A pre-training assessment tool for home dialysis (JPAT).
AB  - A tool for assessing the suitability of candidates for home dialysis (Jo-Pre
      training Assessment Tool version 2.1 - JPAT) was developed, pilot-tested at one
      hospital and field-tested at two major teaching hospitals in Sydney. JPAT acts as
      a screening instrument to distinguish suitable candidates for the home dialysis
      programme, identifying patients with the greatest chance of learning to manage
      the programme. This study included an interview/test of home dialysis patients
      based on the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36).
      JPAT version 2.1 is in the form of an interview questionnaire consisting of 38
      assessment items in six domains: physical stability, nutritional status,
      communication ability, ability to maintain self-care, psychological suitability
      and social support. Overall, results suggest that JPAT version 2.1 is
      sufficiently reliable to be used as a tool for assessing patients who suffer from
      end-stage renal disease (ESRD), and to identify patients most likely to succeed
      in a home dialysis programme.

PMID- 16083023
TI  - The influence of varying blood and dialysate flow on haemodialysis adequacy.
AB  - The aim of this study was the exploration and correlation of the influence of
      variations in blood flow and dialysate flow on haemodialysis adequacy through the
      quantitative indexes Kt/V, TACurea and PCR. A prospective study of 48 patients
      subjected to haemodialysis was carried out. The collection of data included
      taking blood and urine samples according to the directives of DOQI, for a total
      of 8 months. Statistical analysis was based on the paired t-test and multiple
      regression analysis. The variations in blood flow and dialysate flow are
      positively related to the variation of the indexes Kt/V, TACurea and PCR and
      consequently to the haemodialysis adequacy both as isolated factors and when
      combined together.

PMID- 16083024
TI  - Haemodialysing at home: the client experience of self-treatment.
AB  - This paper reports a study that sought to describe the experience of people using
      home haemodialysis as their modality of renal replacement therapy. The study
      employed a critical interpretive methodology. After developing a framework for
      the research, a small group of renal clients who haemodialyse themselves in their
      own homes were intensively interviewed. This study describing the renal client
      perspective indicates that, although more demanding for them than in-centre
      treatment, self-treatment at home can enable a superior quality of life for many
      people living on dialysis.

PMID- 16083025
TI  - The conductivity of dialysis fluid.
AB  - Dialysis fluid consists of a solution of inorganic salts that are dissociated in
      electrically charged ions. These ions can move in an electric field giving the
      salt solution electrically conducting properties, called conductivity. The
      conductivity of the dialysis fluid is a parameter well suited for measuring the
      total concentration of salt. The conductivity is easy to measure with reasonable
      accuracy and the measuring device is usually very stable over time. It can be
      used for both proportioning and monitoring of the concentrate intermixing. The
      conductivity behaviour of a salt solution is however complicated and depends in a
      non-linear way on temperature, total salt concentration and salt/glucose
      composition. The accuracy of the conductivity measurement is given by the
      calibration. A successful calibration requires good knowledge about the measuring
      device and the calibration solutions.

PMID- 16083026
TI  - Quality of life perceived by chronic haemodialysis patients and family members.
AB  - In this study quality of life perceived by 100 haemodialysis patients with family
      members' viewpoints on the patients' quality of life was studied. The SF-36 was
      used as the main measurement tool. According to the findings of the study the
      quality of life scores, perceived by patients, usually ranged between average and
      below average. The family members perceived patients' social functioning and
      functional status in the SF-36 more pessimistically but vitality and well-being
      in the SF-36 more optimistically, when compared to the patients. In the light of
      the findings obtained from the study, it is suggested to periodically assess the
      quality of life of haemodialysis patients considering the viewpoints of family
      members on the patients' quality of life.

PMID- 16083027
TI  - The effect of terror on patients and staff in the dialysis department.
AB  - This study aims to explore the influence of national terror on patients and staff
      in the dialysis department at Haemek Medical Center in Afula, Israel. The staff
      as well as the served population include Jews and Arabs and until lately the only
      fight was against sickness. This study employs a qualitative methodology, based
      on the phenomenological tradition. Semi structured interviews were used for
      collecting the data. Eleven patients and 5 staff members were interviewed.
      Thematic analysis revealed three main themes: 1) Shock: experiencing fear of a
      terror attack, 2) The human becomes 'a robot' and 3) The effect of terror on
      relationships in the department.

PMID- 16083028
TI  - European practice database: results from Greece.
AB  - The survey (EPD) took place during December 2002-January 2003 and presents renal
      care in Greece. A questionnaire, structured at European level and translated into
      Greek, was sent to all dialysis centres (114) by post. The questionnaire was
      returned from 74 centres (64.9%). Some important results were: low use of
      peritoneal dialysis (13.3%), half of PD patients over 65 years old, one ninth of
      patients on transplantation waiting list, isolation for HBV positive patients
      (less for HCV and HIV), high use of AV fistulae (71.2%), maintenance and repair
      of dialysis machines by company technicians, absence of renal dieticians and
      social workers (but availability from hospital employees) one nurse every 5.54
      patients (3.72 if nurse assistants are included), disinfection between shifts
      carried out chemically (hot or cold) and puncturing of vascular access performed
      mainly by nurses and nurse assistants. Data can be used to pressurise government
      for more scientists in the multidisciplinary team to be hired in hospitals,
      develop further research topics and to develop continuous education programmes.

PMID- 16083029
TI  - The European practice database (EPD): results of the study in thte North-East of
      Italy.
AB  - The survey, realized in 2002-03 in the North-East of Italy, describes renal care
      in dialysis services. A questionnaire, structured at European level, was sent to
      all dialysis centres by mail. The questionnaire was returned from 21 centres
      (61.8%) and related satellite units. Results show nonhomogeneity in renal care.
      Some important results were: low use of peritoneal dialysis (18%), compared to
      the rest of Europe, elevated presence of older people on haemodialysis, reduced
      percentage of patients on transplantation waiting list, diffused use of isolation
      for HCV positive patients, high use of AV fistulae (84%), low employment of renal
      technicians, absence of renal dieticians and social workers and nurses performing
      prevalently direct care. Data can be used for different goals: benchmarking
      activities, selection of deeper research topics and development of more oriented
      continuous education activities.

PMID- 16083030
TI  - Paediatric access care: a new collaboratorative research project.

PMID- 16083031
TI  - [Long-term usefulness and safety of the contemporary balloon catheter].
AB  - OBJECTIVE: To evaluate usefulness and safety of an indwelling contemporary
      balloon catheter, we compared complication rates among five methods of urinary
      tract management. PATIENTS AND METHODS: History of febrile episode, bladder
      stones, pyuria and the miscellaneous urinary tract problems of 114 patients were
      retrospectively reviewed. The rates of complications were compared among five
      types of urinary tract management as clean intermittent catheterization dry (not
      incontinent) (CIC-dry: n = 33), clean intermittent catheterization with
      incontinence (CIC-wet: n = 16), clean intermittent catheterization with a
      contemporary balloon catheter indwelling at night (Contemporary catheter: n =
      20), a suprapubic cystostomy catheter indwelling (Cystostomy: n = 22) and
      permanent urethral balloon catheter indwelling (Urethral catheter: n = 24). The
      contemporary balloon catheter used consisted of a reusable balloon catheter and a
      reservoir to inflate the balloon. The patients in the Contemporary catheter group
      self-inserted the catheter every night before sleeping, and then removed it in
      the next morning. After use, the catheter was washed with tap water, and stored
      in a special purpose case filled with disinfectant. RESULTS: The mean follow up
      period was 41 months. The incidence of febrile episode in CIC-wet was 3.36
      times/100 months, Urethral catheter was 2.96, Cystostomy was 1.26, Contemporary
      catheter was 0.57, and CIC-dry was 0.42. The incidence of febrile episode in CIC
      wet and Urethral catheter were significantly higher than in CIC-dry (p<0.05). The
      incidence of bladder stone in Urethral catheter was 1.11 times/100 months,
      Cystostomy was 1.05, Contemporary catheter was 0.96, CIC-wet was 0.61, and CIC
      dry was 0.21. The Urethral catheter group had significantly higher incidence of
      bladder stone than CIC-dry (p<0.05). CONCLUSIONS: The indwelling contemporary
      balloon catheter is recommended for long-term use in CIC-wet group.

PMID- 16083032
TI  - [Effectiveness of neoadjuvant chemotherapy for the patients with locally invasive
      bladder cancer].
AB  - OBJECTIVE: To know the survival and prognostic factors of the patients who
      received radical cystectomy with or without neoadjuvant cisplatin-based
      chemotherapy. METHODS: Between 1977 and 2001, 201 patients underwent radical
      cystectomy at Yokohama City University and Yokosuka Kyosai Hospital whose tumor
      were clinically diagnosed as locally invasive bladder cancer (T2-4NxM0). Survival
      rates and 9 prognostic factors (Age, Size, Multiplicity, Type, Grade, p-stage,
      n,neoadjuvant chemotherapy, adjuvant chemotherapy) were analysed by Kaplan-Meier
      methods and Cox-proportional hazard model. RESULTS: The independent prognostic
      factors of these patients were size, multiplicity, type, grade, p-stage, n,
      neoadjuvant by univariate analysis. Of these 7 factors, n, neoadjuvant, p-stage
      and size are significant by multivariate analysis. Survival of the patients who
      received neoadjuvant cisplatin-based chemotherapy followed cystectomy is better
      than cystectomy only group by Kaplan-Meier method. CONCLUSIONS: From these
      rusults, neoadjuvant cisplatin-based chemotherapy play some role for survival of
      the patients with invasive bladder cancer.

PMID- 16083033
TI  - [Clinical evaluation of 30 patients with interstitial cystitis complicated by
      fibromyalgia].
AB  - PURPOSE: Although interstitial cystitis (IC) complicated by fibromyalgia (FM) is
      yet unreported in Japan, we encountered patients with the complications almost as
      frequently as in the USA. We report the present status of such patients and the
      significance of this complication. PATIENTS AND METHODS: We evaluated the
      clinical findings of 30 patients with IC complicated by FM in the last four
      years. RESULTS: Average IC symptom index and problem index was 14.9 and 14.6,
      respectively. Average numbers of tender points for the criteria for FM was 16
      locations. Both diseases have some similarities in the decrease in pain
      threshold, extensive pain, factors exacerbating symptoms and treatment methods.
      CONCLUSION: Approximately 11% of patients with IC have a complication of FM. They
      feel isolated due to the lack of understanding of the disease and endure
      generalized intolerable pain.

PMID- 16083034
TI  - [Sudden death after 125I brachytherapy in prostate cancer patient: a case
      report].
AB  - A management of 125I isotope is defined by medical guideline from Ministry of
      Health, Labour and Welfare in Japan. According to this, when the patient died
      within one year after 125I interstitial permanent prostate brachytherapy, we have
      to do autopsy and collect all implanted isotopes as soon as possible. We report
      here, a 70-year-old man who underwent 125I interstitial permanent prostate
      brachytherapy for localized prostate cancer and one month after brachytherapy the
      patient died of acute cerebral hemorrhage, which was unrelated to the 125I
      brachytherapy. Autopsy was performed and collection of migrated isotopes was
      extremely difficult in technically. In addition, the cost of autopsy and distance
      from our hospital were also problems in this case. Treatment of prostate cancer
      with brachytherapy has increased in Japan, and we should establish management
      manual for sudden death case after 125I brachytherapy.

PMID- 16083035
TI  - [Intraluminal ureteral hematoma complicating anticoagulant therapy].
AB  - Intraluminal ureteral hematoma is a rare disease and only a few cases have been
      previously described. We report a case of intraluminal ureteral hematoma induced
      by anticoagulant therapy. A 65-year old man having the oral anticoagulant therapy
      for prevention of secondary thrombolism following atrial fibrillation was
      referred to us for gross hematuria. Ultrasound sonography (US) revealed right
      renal mild wide pelvis. Computed tomography (CT) showed the right ureteral
      submucosal hematoma. This ureteral hematoma penetrated the ureteral mucosa and
      caused macrohematuria. The patient had been anticoagulated on Warfarin with
      Bucolome for 18 days, so the prothrombin times (PT) was found to be excessively
      prolonged beyond the normal therapeutic range. The oral anticoagulation was
      stopped and intravenous Vitamin K2 was given, so PT was normalized. Though
      estimate hemorrhage quantity reached 1,200 ml, we had no blood transfusion. The
      hematoma was completely diminished 4 months later, no reccurence has been
      occurred. Bucolome has especially pharmacokinetic positive interaction to
      Warfarin, so we must check PT-INR frequently.

PMID- 16083036
TI  - [Bladder stone caused by olive oil following TVT operation].
AB  - Tension-free vaginal tape (TVT), a less-invasive variation of the suburethral
      sling, has been rapidly gaining popularity worldwide in the treatment of female
      stress urinary incontinence. We report on two cases of bladder stones composed of
      fatty acid calcium following TVT operations. Case 1: A 76-year-old woman with a
      history of hysterectomy due to cervical cancer was suffering from vault prolapse.
      The insertion of a ring pessary lead to the development of stress urinary
      incontinence, and she was referred to our hospital. As she was frail, sexually
      inactive, and elderly, she underwent partial colpocleisis (Le Fort operation)
      combined with a TVT operation. One-month postoperative videourodynamics and chain
      cystourethrography (CUG) using olive oil as the lubricant showed cure of
      incontinence and mild support of the urethra. Her maximum flow rate was 18.8 ml/s
      and no residual urine was observed. Six months postoperatively she developed
      postmiction pain and pyuria that were not improved by antibiotics. Cystoscopy
      showed a small bladder stone, whose removal cured cystitis. Case 2: A 49-year-old
      woman, with a history of abdominal hysterectomy due to myoma uteri, visited our
      hospital complaining of stress urinary incontinence. A periurethral collagen
      injection was only temporarily effective, and she underwent a TVT operation. A 1
      month postoperative evaluation including chain CUG using olive oil as the
      lubricant showed cure of incontinence, mild support of the urethra, a maximum
      flow rate of 28.8 ml/s, and no residual urine. Two months postoperatively she
      developed miction pain and pyuria that were solved by removing a small bladder
      stone. Anti-incontinence surgery increases the risk of developing bladder stones
      due to either foreign bodies (bladder erosion) or obstruction. However, neither
      of our cases had these conditions; instead, both bladder stones were composed of
      fatty acid calcium that appeared to be related to the olive oil used as the
      lubricant in chain CUG. Only four cases (including ours) of bladder stones
      composed of fatty acid calcium have been documented, but they may indicate that
      care is necessary when using olive oil as a contrast medium or lubricant in the
      urinary tract. When a woman with a history of anti-incontinence surgery has
      persisting or recurrent cystitis, cystoscopy should be performed to exclude
      bladder erosion and stones.

PMID- 16083037
TI  - [A case of small cell carcinoma of kidney; solitary splenic metastasis].
AB  - A 67-year-old male visited a hospital with a complaint of right flank pain. A
      computed tomography and magnetic resonance imaging demonstrated a right renal
      tumor, lymphadenopathy, and a splenic tumor. Right radical nephrectomy, lymph
      node dissection, and splenectomy were performed. Histological examination of the
      renal tumor and lymph node revealed small cell anaplastic carcinoma. A dilated
      renal pelvis was focally covered with transitional cell carcinoma grade 2.
      Splenic tumor revealed a mixture of small cell and giant cell anaplastic
      carcinoma. Immunostaining for NSE and cytokeratin were positive. He received 2
      courses of adjuvant chemotherapy with cisplatin and etoposide. The patient is
      alive for 10 months after surgery and free of carcinoma. This is the 10th case of
      renal small cell carcinoma reported in Japan. The clinical features and
      managements of these rare tumors are discussed.

PMID- 16083039
TI  - [Chemical genomics: the world of biology explored by chemistry].

PMID- 16083038
TI  - [A modified retroperitoneal approach to the kidney in patients with a highly
      deformed thorax: obtaining a wide operative field through subperiosteal resection
      of the 10th, 11th and 12th ribs].
AB  - We herein report a technique which facilitates a retroperitoneal approach to the
      kidney in cases of highly deformed thorax due to kyphoscoliosis. The operation
      consists of a lumbar oblique incision with removal of the 11th rib, combined with
      the additional removal of the 12th and 10th ribs. Resection of the upper two ribs
      was performed subperiosteally, leaving the periosteum of the deep side untouched.
      However, the deep side periosteum of the 12th rib was incised caudal from the
      pleural margin in order to facilitate exposure of the diaphragm. The
      retroperitoneal space was entered through the tip of the 11th rib bed. The
      diaphragm was incised dorso-medially at a level 1 cm caudal from the lower margin
      of the pleura, to an extent necessary to enable the pleura together with the
      cranial diaphragm to be manoeuvred in an upward direction. Two cases with renal
      tuberculosis associated with high-grade kyphosis and one case with staghorn
      calculi accompanied with lordosis were operated on utilizing this technique. In
      the former two cases, the thoracic cage was in direct contact with the iliac bone
      and there was practically no space between the rib border and the iliac crest.
      This was also true of the third case, but the grade of deformity was not as
      extensive as in the former two cases. Removal of the 10th, 11th and 12th ribs
      could be achieved without injuring the pleura and a satisfactorily large
      operating field could thus be developed which enabled a simple nephrectomy to be
      performed without difficulty. The characteristic feature of the described
      approach is that resection of the 10th and 11th ribs is simply to facilitate
      manoevrability of the wound margin, without going through the rib bed. The
      technique could be advantageous in selected cases where there is a highly
      deformed thorax.

PMID- 16083040
TI  - [Forward and reverse chemical genetics utilizing naturally occurring bioprobes].

PMID- 16083041
TI  - [Trends in chemical libraries for chemical genetics].

PMID- 16083042
TI  - [Chemistry and biology of NAD-dependent deacetylases].

PMID- 16083043
TI  - [Chemical genomics on new angiogenesis inhibitors].

PMID- 16083044
TI  - [Pioneering chemical space in drug discovery research: application of
      transcriptomic and quantitative proteomic analyses].

PMID- 16083045
TI  - [Chemical genomics by post-genomic approaches using Schizosaccharomyces pombe].

PMID- 16083046
TI  - [ANP receptor structure and signal transduction mechanism: a novel hormone
      induced rotation mechanism for transmembrane signaling].

PMID- 16083047
TI  - [Structure and function of Formin homology 2 domain].

PMID- 16083048
TI  - [Transmission of tuberculosis (III)].
AB  - Tuberculosis outbreak is defined as group infection more than 20 persons had been
      infected with tubercle bacilli in Japan, provided one person developed disease is
      counted as 6 persons had been infected. Outbreak is to be reported compulsory to
      the Ministry of Health, Welfare and Labor. A total of 365 outbreaks of
      tuberculosis have been reported in these 10 years during 1994 and 2004. Out of
      them, large scale outbreak more than 10 persons have developed disease were 41
      (11.2%). Results of contact surveys has reported that 0.36% of newly registered
      smear positive cases had caused tuberculosis outbreak, 1.1% had resulted small
      scale group infection (5 to 19 persons had been infected), although majority of
      the bacteriology positive cases didn't infected even one person. To make clear
      the mode of airborne infection with tubercle bacilli more clearly, the author has
      discussed the results of quantitative model on droplet nucle infection by Riley
      RL and others, nosocomial infection of smallpox virus in Germany in 1970, the
      results of analysis of airflow at the sites of outbreaks at business office and
      middle school in Japan, and so on. Finally, the author has reviewed the
      development of research on annual risk of tuberculosis infection in Japan and
      discussed about the present problems of risk of tuberculosis infection in Japan.

PMID- 16083049
TI  - [Coexistence of lung cancer and active pulmonary mycobacteriosis].
AB  - OBJECTIVES: The aim of this study is to clarify the clinical and pathological
      anatomical picture of cases in which lung cancer and active pulmonary
      mycobacteriosis are intermingled in the same lobe of the lung. MATERIALS AND
      METHODS: We analyzed clinicopathological data on 11 cases in which lung cancer
      and active pulmonary mycobacteriosis are intermingled in the same lung lobe out
      of 61 admitted cases of coexisting lung cancer and active pulmonary
      mycobacteriosis, encountered at National Hospital Organization Tokyo National
      Hospital during the period from 1991 to 2003. RESULTS: The subjects were 10 men
      and 1 woman, with a mean age of 68 years. The species of mycobacteriosis were M.
      tuberculosis in 6 and nontuberculous mycobacteriosis in 5 (M. avium disease and
      M. abscessus disease in 2 each, and M. kansasii disease in 1). The frequency of
      the mixture was 13% (6/45) in patients with lung cancer and tuberculosis and was
      31% (5/16) in patients with lung cancer and nontuberculous mycobacteriosis.
      Radiographic findings revealed that both cancer shadows and mycobacteriosis
      shadows are identified in 8 of the 11 patients, whereas cancer shadows were
      recognized but mycobacteriosis shadows could not be pointed out in the remaining
      3 patients. We divided 7 cases (5 resection scases and 2 autopsy cases) with the
      mixture of cancer and mycobacteriosis into 2 types from the macroscopic images:
      (1) type A (4 cases, the foci of lung cancer and tuberculosis, which were
      separated originally, progressed mutually, and has adjoined), and (2) type B (2
      cases, the foci of mycobacteriosis existed within or in the edge of the foci of
      lung cancer). There were 3 nontuberculous mycobacteriosis cases and 1
      tuberculosis case in type A, and 2 tuberculosis cases and 1 nontuberculous
      mycobacteriosis in type B. In nontuberculous mycobacteriosis cases, cancer and
      mycobacteriosis had often adjoined under the conditions of preexisting lung
      disease, such as a lung cyst, whereas in tuberculosis cases, it was
      characteristically shown that the wall of encapsulated caseous nodules was
      destroyed by cancer invasion, and that the tuberculous nodules were reactivated.
      These findings seemed to be related to exogenous infection of nontuberculous
      mycobacteriosis to the injured lungs and to endogenous reactivation of
      tuberculosis from inactive tuberculous lesions. CONCLUSION: Lung cancer and
      active pulmonary mycobacteriosis are often seen intermingled in the same lung
      lobe, and the mixture pictures of the two diseases are variable. The physicians
      should carefully note about the mixture of lung cancer and mycobacteriosis,
      though the findings are not clear on the chest plain radiographs.

PMID- 16083050
TI  - [Management of asymptomatic newborns with periportal hypodensity and high serum
      IgM who were born from untreated tuberculosis mothers].
AB  - OBJECTIVES: We previously reported the presence of periportal hypodensity on CT
      image in two newborns and an early infant with congenital tuberculosis as an
      adjunct diagnostic option. The aim of this study was to determine the degree of
      treatment based on both periportal hypodensity and serum IgM presented in
      asymptomatic newborns born from tuberculosis mothers. SUBJECTS AND METHODS: Eight
      newborns born from mothers with untreated tuberculosis between 1996 and 2002 were
      retrospectively studied. Newborns who presented periportal hypodensity and high
      serum IgM were treated with anti-tuberculosis medicines, combination of isoniazid
      and rifampicin for nine to 12 months with streptomycin in the initial two months,
      and the outcomes of the treatment were followed for at least two years. RESULTS:
      All eight newborns had gastric aspirates negative for Mycobacterium tuberculosis.
      Three of eight newborns (38%) demonstrated periportal hypodensity, and they also
      demonstrate a tendency of high serum IgM. None of these three newborns treated
      with combination of isoniazid, rifampin, and streptomycin for 9 to 12 months
      developed tuberculosis during the observation period. CONCLUSIONS: These results
      suggest that presence of both periportal hypodensity and high serum IgM in
      asymptomatic newborns born from mothers with untreated tuberculosis may be one of
      risk factors of developing congenital tuberculosis, and that anti-tuberculosis
      treatment for nine to 12 months may prevent them from the disease development
      despite possible criticism of overdiagnosis and overtreatment.

PMID- 16083051
TI  - [Two cases of Mycobacterium szulgai pulmonary disease in the elderly].
AB  - The rate of pulmonary nontuberculous mycobacteriosis (NTM) in the total pulmonary
      mycobacteriosis has been continuously increasing. While M. avium complex is the
      most common cause of NTM, there are a few case reports of pulmonary infection due
      to M. szulgai. We described two cases of pulmonary NTM caused by M. szulgai. A 75
      year-old male was admitted to our hospital because of dyspnea on effort, and
      productive cough. A chest X-ray showed an infiltrative shadow with cavity in the
      right upper lobe. A sputum smear for mycobacteria was positive, and a culture
      grew M. szulgai which was identified by DNA-DNA hybridization. He was treated
      with isoniazid, rifampicin, and ethambutol. His symptoms and CT and X-ray
      findings improved, and his sputum smear and culture converted to negative for
      mycobacteria. Second case was a 73-year-old male who had previously been
      diagnosed as MAC and pulmonary aspergillosis, and had been treated with
      antituberculous and antifungal drugs. He was readmitted to our hospital, because
      of general fatigue and hemoptysis. A chest X-ray revealed a consolidation with
      bronchiectasis and cavity in the both upper lung fields. A sptum smear for
      mycobacteria was positive, and a grown culture was identified as M. szulgai. He
      was treated with rifampicin, ethambutol and kanamycin based on the results of
      susceptibility testing. After 3 months of this treatment his sputum smear and
      culture converted to negative for mycobacteria, and his symptoms, and CT and X
      ray findings improved.

PMID- 16083052
TI  - Suppressive effects of Calendula micrantha essential oil and gibberelic acid
      (PGR) on repro ductive potential of the Mediterranean fruit fly Ceratitis
      capitata Wied. (Diptera: Tephritidae).
AB  - The volatile oil of Calendula micrtantha plant was extracted and the components
      were identified by Gc/Ms. Adulticidal efficiency of the volatile oil and
      gibberelic acid "plant growth promoting hormone" as well as their mixture was
      assessed against the Mediterranean fruit fly Ceratitis capitata. The result
      showed that the two compounds capable have characteristic resembling to insect
      juvenile hormones and have suppressive effect on reproductive potential. They
      induced the significant disturbances in the ovarian protein fraction and the
      amino acids patterns.

PMID- 16083053
TI  - Trichinella spiralis: affinity purified antigen based diagnosis and
      immunoprophylaxis.
AB  - The current research introduces a trial to develop vaccine candidate against
      trichenosis. A method of affinity chromatography was adopted to purify a
      Trichinella spiralis larval extract. The isolated fraction resolved into six
      bands of 148 KDa, 133 KDa, 118.5 KDa, 101 KDa 98.5 KDa and 79.5 KDa as observed
      by SDS-PAGE. The diagnostic value of this fraction was checked against antibodies
      regularly collected from rats experimentally infected with trichinosis compared
      with that of crude larval extract by ELISA. The crude extract detected the
      antibodies as early as one week post infection and the maximum level was recorded
      four weeks post infection. The advantage of the isolated fraction over the crude
      extract in trichinosis diagnosis was clearly observed at high serum dilution
      reached to 1:4000. The protective value of the isolated fraction was also
      investigated. Rats immunized subcutaneously with affinity purified larval extract
      with Freund's adjuvant showed reduction in worm burden reached to 82%. IgG
      antibody response in immunized rats was higher than that of control infected
      animals as measured by ELISA. This response might be partially responsible for
      the observed protection.

PMID- 16083054
TI  - Prevalence of Blastocystis hominis among "healthy" food handlers in Dammam, Saudi
      Arabia.
AB  - A prospective study was carried out to see the prevalence of B. hominis in food
      handlers in Dammam, Eastern Province of Saudi Arabia. A total of 17073 food
      handlers were examined, 8.50% persons were positive for this organism in their
      stool. In 2.4% of the food handlers, B. hominis was the only parasite, whereas in
      1.9% and 4.2% of the cases, this organism was found in association with
      pathogenic and non pathogenic parasites respectively. We could find the
      correlation between the dietary habits and the presence of organism in stool. In
      19.9% of the positive food handlers in whom rice was the predominant food the
      organism was seen, when compared to 80.1% of the predominantly wheat eaters.

PMID- 16083055
TI  - Effect of interferon-alpha on experimental Schistosoma mansoni infection in mice.
AB  - To investigate the immunomodulatory effect of the Th1 mediated cytokine IFN-alpha
      on schistosomiasis, this cytokine was weekly injected into mice experimentally
      infected with S. mansoni, beginning from day 0 (group II), week 3 (group III),
      week 6 (group IV) and week 10 (group V) post-infection. TGF-beta1 serum levels
      were estimated on a weekly basis and beginning one week after initiation of IFN
      alpha therapy, while all animals were sacrified on week 14 to be used for egg
      counts in liver and small intestine, oogram study for determination of the
      maturity of deposited eggs, and histopathological examination of stained liver
      sections. IFN-alpha treated groups were characterized by a more intense
      oviposition in the intestine (liver/intestine ratio less than 1), with higher egg
      numbers the earlier IFN-alpha was administered. Oograms of the intestine
      indicated the level of immature eggs to be statistically significantly higher in
      group II, III and IV than in the control group I (p < 0.05). In IFN-alpha
      medicated mice, the mean numbers and diameters of hepatic granulomas were less
      than in GI, in addition to a lower representation of fibrocellular and fibrous
      granulomas among them (all parameters p < 0.05), especially in Gs IV & V. The
      inflammatory cell population in the form of eosinophils, histiocytes and giant
      cells was more pronounced in Gs III, IV & V. TGF-beta1 serum levels showed a
      progressive rise, however more pronounced in the untreated control. A
      statistically positive significant was established between TGF-beta1 levels and
      number, size and percentage of fibrotic hepatic granulomas in all groups.

PMID- 16083056
TI  - Human fascioliasis and anaemia in Dakahlia Governorate, Egypt.
AB  - Fasciola infection (fascioliasis) appeared to be endemic in Egypt. Stool samples
      of fourty eight patients were coprologically diagnosed. According to Fasciola egg
      counting per gram stool, the severity of infection was divided into light
      infection in 60.5%, moderate in 27.1% and severe infection in 12.5%. No
      significant correlation was detected between severity of infection and patients'
      sex. Complete blood picture, reticylocytic count, serum iron, immunological
      assays as anti-nuclear, anti-smooth muscle antibody, anti-mitochondrial anti
      body, anti-DNA tests and rheumatoid factor and occult blood in stool were
      investigated. Normocytic normochromic anaemia was detected in 62.5% of the
      fascioliasis patients, microcytic hypochromic anaemia in 31.3% and macrocytic one
      in 6.3%. Highly significant negative correlation (R = -0.68) was detected between
      haemoglobin concentration and egg count per gram faeces. Human fascioliasis was
      associated with normocytic normochromic anaemia and to a lesser extent microcytic
      hypochromic anemia.

PMID- 16083057
TI  - Congenital trichinellosis in experimentally infected mice.
AB  - The present study aimed at allocating the time during pregnancy at which
      transplacental transmission of Trichinella spiralis (T. spiralis) larvae took
      place. Swiss albino mice were infected at different durations of pregnancy; five
      days before mating, on gestation day zero and five days after mating.
      Furthermore, to study the effect of immunosuppression on transplacental
      transmission, half of the experimental mice were immunosuppressed using
      cyclophosphamide drug (Endoxan). The percentage of infected uteri, embryos and
      placentas and the mean larval count were calculated on day 8 post infection (PI).
      Moreover, the percentage of infected offspring and the mean larval count in their
      muscles were estimated on day 30 PI. The results of the present study revealed
      that, transplacental transmission of T. spiralis could occur in offspring of mice
      when their mothers are infected before or after pregnancy. This was documented by
      the presence of larvae in the muscles of offspring. However, the rate of this
      transmission increased when the mothers are infected at late pregnancy whether
      they were immunosuppressed or not. The administration of the immunosuppressive
      drug whether before or after pregnancy increased the rate of infection and the
      mean larval count in both uteri of mothers and muscles of their offspring. A
      higher percentage of abortion was demonstrated in females infected before mating
      in different studied groups.

PMID- 16083058
TI  - Incidence of Nematodirus species and their differentiation through the infective
      third stage larvae among Egyptian camels.
AB  - Coprological examination on camels (Camelus dromedarius) from different
      localities in Egypt revealed the presence of Nematodirus eggs in 38 out of 312
      (12.18%). The faecal samples positive to Nematodirus eggs were cultured for
      collection of infective third stage larvae (L3). Details of the general and
      differential categories of each sample were given. The recovered species were
      Nematodirus battus, Nematodirus filicollis and Nematodirus spathiger.

PMID- 16083059
TI  - The liver function profile in PCR-RNA Egyptian HCV-patients and normal controls.
AB  - No doubt, Hepatitis C virus (HCV) is a real health problem worldwide. The liver
      function tests (S.ALT, S.AST, Albumin, Total Protein, Total Bilirubin and Direct
      Bilirubin) were evaluated in 20 PCR-RNA positive HCV-patients and 10 cross
      matched apparently healthy population. All the HCV-patients and controls were
      free from liver helminthes. The results showed that in the HCV-patients, there
      was elevation in the level of S.ALT (17/20 or 85%), S.AST (20/20 or 100%), Total
      Bilirubin (7/20 or 35%), and (4/20 or 20%). Besides, there was neither a
      correlation between sexes nor the degrees of viraemia and the elevation of these
      four parameters. However, serum levels of Albumin, and Total Protein were within
      the normal range. On the other hand, in the controls the levels of the six tests
      were within the normal range. Nevertheless, only one control subject who had
      positive HBs-Ag, showed elevated Total Bilirulin and Direct Bilirubin.
      Consequently, these tests are indicative as useful and dependable markers in the
      non-invasive diagnosis of the hepatitis C virus (HCV).

PMID- 16083060
TI  - Quantitative comparison of infected Schistosomiasis mansoni and Haematobium:
      animal model analysis of the granuloma cell population.
AB  - To evaluate the hypothesis that the granuloma cell population in S. haematobium
      is different from that of S. mansoni infections, a hamaster animal model was
      established. Infection of hamesters was induced by abdominal skin exposure of
      male golden hamsters with 300 cercariae. S. haematobium granuloma cell population
      in the small intestine, urinary bladder, liver and spleen and those of S. mansoni
      granuloma in the small intestine and liver of infected hamsters were
      histologically examined between 6 and 12 weeks post-exposure. In both species,
      the granuloma cell population was fomed of lymphocytes (47%), histiocytes (28%),
      eosinophils (16%) and polymorphs (8%). As compared to granuloma cell population
      in S. haematobium; S. mansoni granulomas had: (a) higher population of
      eosinophils (28% vs. 11%), (b) lower population of polymorphs (4% vs. 10%) and
      histiocytes (22% vs. 31%) and (c) similar population of lymphocytes (46% vs.47%).
      The mean diameter of liver granuloma was higher in S. mansoni (175.8 +/- 12.34)
      than for S. haematobium (125.4 +/- 16.12). As compared to S. haematobium, the
      numbers of isolated male, female and total worms were significantly higher in S.
      mansoni (24.5 +/- 2.7 vs. 7.3 +/- 2.3; 6.3 +/- 0.8 vs. 2.2 +/- 0.5; 80 +/- 2.2
      vs. 56.3 +/- 3.8, p < .0.05). The heterogeneity of cell population in granuloma
      suggests the involvement of different immune mechanisms in their development. The
      cells achieving numerical dominance in the granulomas were in the following
      order: lymphoyctes > monocytes > eosinophils > polymorphs. The differrence in the
      granuloma cell population between S. haematobium and S. mansoni may reflect
      different tissue reactions to the deposited ova.

PMID- 16083061
TI  - Update of fasciolosis-transmitting snails in Egypt (review and comment).
AB  - Several snail species may contribute in transmission of fasciolosis in Egypt.
      These molluscs show a variable sensibility to natural infections with Fasciola
      species. Radix natalensis is considered to be the essential intermediate host for
      F. gigantica based on field and experimental studies. Cercarial production from
      R. natalensis experimentally infected with F. gigantica is affected by the
      species of definitive host from which the eggs are obtained, as well as the
      different laboratory conditions. Another lymnaeid, Galba truncatula, may play a
      role in transmitting this parasite in Egypt, as it was found naturally infected
      with F. gigantica. Latter snail species, originated from France, was susceptible
      to experimental infections with Egyptian miracidia of F. gigantica and it had a
      cercarial production close to that of local R. natalensis. Two other snails,
      Pseudosuccinea columella and Biomphalaria alexandrina, were naturally found
      harboring larvae of Fasciola sp. At the level of intermediate hosts of F.
      gigantica, the conditions are thus favorable in Egypt to transmit fasciolosis
      which could also be caused by another fasciolid, F. hepatica, as the existance of
      this fluke was confirmed in Egypt.

PMID- 16083062
TI  - Ascaris in gallbladder: report of a case and review.
AB  - A case of an Ascaris infection of the gallbladder is reported in a 29 years old
      female. The biological check-up was normal. The diagnosis was confirmed by
      ultrasonography and the patient was cured by albendazole. Such a localization is
      uncommon (2.1% of the hepatobiliary ascariasis), and the abdominal
      ultrasonography is the best way to confirm the diagnosis. Albendazole is the
      current treatment, but cholecystectomy is sometimes a must.

PMID- 16083063
TI  - Identification and diagnostic evaluation of cross-reactive antigen between
      hydatid cyst fluid of Echinococcus granulosus and Trichinella spiralis larval
      extract.
AB  - A cross reactive fraction was isolated from hydatid cyst fluid antigen of E.
      granulosus using CNBr Sepharose 4B affinity chromatography in which anti-T.
      spiralis antibodies were coupled with the column. Biochemical characterization of
      the isolated fraction included the use of SDS-PAGE, isoelectric focusing and
      amino acid analysis. The fraction showed 5 polypeptides of 165, 95.5, 63.5, 30.6
      and 24 KDa. The isoelectric points of these polypeptides were 7.8, 7.2, 6.7, 6.2
      and 5.7. The fraction exhibited 17 amino acids and was rich in tyrosine (20.81)
      and glutamic (15.28) ug/100 mg. The fraction proved higher potency in the
      diagnosis of experimental trichinellosis in rats than echinococcosis in dogs by
      ELISA. All experimentally infected animals reacted positively, recording 100%
      diagnostic sensitivity. Collectively, the present study proved that the hydatid
      cyst fluid cross-reactive fraction could be used in the diagnosis of
      trichinellosis at different intervals of infection and as early as 1 week post
      infection.

PMID- 16083064
TI  - Effect of Nigella sativa and Allium cepa oils on Trichinella spiralis in
      experimentally infected rats.
AB  - Prophylactic and therapeutic effect of two oils had been carried out either prior
      to infection or postinfection respectively in rats. Each rat in either case was
      orally administered with N. sativa oil or A. cepa oil in a dose 5 mg/kg body
      weight/day for 2 weeks. Assessment of results was by: (1) adult worm count in the
      intestine on 7th and 20th day post infection. (2) larval count in the muscles on
      the 60th day post infection. (3) Index of reproductive capacity. (4) Detection of
      antibodies against T. spiralis larvae by using ELISA. The results showed that, N.
      sativa oil as prophylactic treatment prior to T. spiralis infection is more
      effective than A. cepa oil on both adult worms and muscle larval count. While, A.
      cepa oil was showed more effectiveness than N. sativa on decline number of adult
      worms and muscle larvae when used as therapeutic treatment post infection. The
      level of antibody was recorded early in the groups that treated with N. sativa
      oil. In conclusion, N. sativa and A. cepa oils have anthelmintic effect in the
      rats infected with T. spiralis infection and increased the production of
      antibodies generated during life cycle of this parasite.

PMID- 16083065
TI  - Partial purification and characterization of Ascaridia galli diagnostic worm
      antigen.
AB  - Partial purification of Ascaridia galli whole worm extract was conducted by
      Cyanogen bromide Sepharose 4B immunoaffinity column chromatography. The resulted
      fraction was characterized by sodium dodecyle sulphate polyacrylamide gel
      electrophoresis (SDS-PAGE) and isoelectric focusing. The fraction was found to be
      consisted of six bands of 207 KDa, 157 KDa. 110 KDa, 103 KDa, 76 KDa and 41 KDa.
      This profile was compared with that of whole worm and excretory-secretory
      antigens. Both antigens were resolved into multiple bands in both high and low
      molecular weight ranges. The isoelectric focusing of the fraction displayed 8
      bands of isoelectric points 7.5, 7.0, 6.8, 6.5, 6.2, 5.8. 5.3 and 4.6. The
      potency of this fraction in the diagnosis of natural ascaridiosis in chickens was
      assessed by ELISA compared with that of whole worm and ES antigens. The affinity
      purified fraction showed higher potentials in the diagnosis of A. galli infection
      in chickens than whole worm antigen at any sera dilution and than ES antigen at
      high sera dilutions. While ES antigen of the worms revealed higher diagnostic
      capabilities than whole worm extract. The current research recommends utilization
      of the affinity isolated fraction in the diagnosis of natural ascaridiosis in
      chickens.

PMID- 16083066
TI  - Effect of parenteral vitamin E and selenium supplementation on immune status of
      dogs vaccinated with subunit and somatic antigens against Taenia hydatigena.
AB  - Thirty clinically healthy dogs were divided into five equal groups; Gs 1 and 2
      were vaccinated with subunit and somatic antigens (Ags) respectively in
      combination with vitamin E and selenium (Vit E/Se) supplement, Gs 3 and 4 were
      vaccinated with subunit and somatic Ags respectively and group 5 was kept
      unvaccinated as control positive. Dogs in the vaccinated-Vit E/Se supplemented
      groups had a significantly greater (P < 0.05) serum Se and alpha-tocopherol than
      un-supplemented Gs. Best immune response against T. hydatigena was observed in
      the Vit E/Se supplemented groups, as evidenced by increase production of antibody
      titer and IgG concentration in comparison with either vaccinated un-supplemented
      or control groups. Moreover, the highest protection level against T. hydatigena
      infection was observed in groups 1 and 2 (83.3%), while was 66.7% and 50% in
      groups 3 and 4 respectively. Subunit Ag was more efficient than somatic Ag in
      improving the immune status of dogs. Vit E and Se proved to be immuno
      potentiating to dogs vaccinated with subunit and somatic Ags and increased the
      possibility for the protection against T. hydatigena infection.

PMID- 16083067
TI  - Nonoxynol 9 as an additive therapy in metronidazole-resistant cases of vaginal
      trichomoniasis.
AB  - The present study was conducted on 30 female patients with metronidazole
      resistant vaginal trichomoniasis to investigate the efficacy of nonoxynol 9 (N
      9), a non hormonal contraceptive with spermicidal effect, as an additive therapy
      to metronidazole (MNZ). Study population were randomly divided into 3 groups
      according to treatment regimen: G.I: patients received high dose MNZ (2 g daily
      for 7 days) n = 10; G. II: patients received (100 mg N-9 vaginal suppository
      daily for 7 days) n = 10; G. III: patients receiving conventional MNZ dose (1 g
      daily for 7 days) plus (a 100 mg N-9 suppository for 7 days) n = 10. Clinical and
      parasitological evaluation of cure was performed at return visits 1, 2, 4 and 6
      weeks post treatment. Negative T. vaginalis vaginal smears were ensured by direct
      microscopic visualization and In Pouch TV culture technique. Most of the patients
      were in the 30-39 years age group (60%) and burning was the most frequent symptom
      (96.67%). The cure rates were 70%, 40% and 90% for Gs I, II & III respectively,
      while adverse effects of treatment were recorded most frequently by patients of
      G.I. So, MNZ resistant trichomoniasis incidence seems to be on the rise. Topical
      therapy alone has a low cure rate while combined oral conventional doses of MNZ
      and intravaginal nonoxynol 9 treatment appears to be a good clinical trial with
      fairly good cure rate thus, avoiding the adverse side effects of high doses MNZ
      therapy and T. vaginalis health hazards potentiality.

PMID- 16083068
TI  - Immunization of mice with crude extract of Saccharomyces boulardii yeast induces
      cross-reactive immune responses with antigenic preparations from different
      developmental stages of the Schistosoma mansoni and reduces the parasite worm
      burden.
AB  - Immunization of mice with Saccharomyces boulardii crude extract caused a
      significant reduction in Schistosoma mansoni worm burden (23.7%; P = 0.02) in
      comparison to control mice. Mice sera collected after the 1st immunization showed
      a significant increase (P < 0.05) in both IgM and IgG against parasite soluble
      cercarial antigenic preparation (CAP) than unimmunized mice sera (UMS). Upon 2nd
      immunization, sera from yeast extract immunized mice (YIM) showed increase of IgM
      and IgG (1.6 and 1 fold) against CAP than UMS. Sera collected 2, 4 and 6 weeks
      (W) after infection of YIM with S. mansoni cercariae showed higher IgM (1.4, 1.5
      and 1 folds) and IgG (0.9, 1.2 and 1.1 folds) levels against CAP than sera of
      infected UM (IUM). When compared to sera from UM, a week post 1st and 2nd
      immunization sera showed a significant elevation (P < 0.05) of both IgM and IgG
      to parasite soluble adult worm antigenic preparation (SWAP). Sera collected at 2,
      4 and 6W after infection of YIM with parasite cercariae showed higher IgM (1.1,
      1.3 and 1.2 folds) and IgG (1.2, 1.1 and 1.3 folds) reactivities against SWAP
      than sera of IUM. One week post 1st and 2nd immunization with the yeast extract,
      sera showed a significant increase (P < 0.05) of both IgM and IgG levels against
      parasite soluble egg antigen (SEA) when compared with sera from UM. At 2 and 4W
      post infection, sera from immunized infected mice showed a significant decrease
      in IgM (P < 0.05) but the decrease of IgG (0.7 fold) was not significant when
      compared to IUM. Six weeks post infection the decrease in both antibodies
      remained but it was significant for IgG (P < 0.05) but not for IgM (2.1 folds)
      when compared with IUM. Immunization with S. boulardii extract caused a non
      significant increase (1.2 folds) in mesenteric lymph node (MLN)-CD4+T cells,
      significant elevation of MLN-CD8+T cells (P < 0.05) and a non-significant
      increase (0.9 folds) of B-cells when compared to that of UM. Also, Immunization
      with S. boulardii extract caused 1 fold elevation in both CD4+ and CD8(+)-T
      lymphocytes in thymus of YIM when compared with their counts in thymus of UM.

PMID- 16083069
TI  - Protective effect of Eimeria stiedae coproantigen against hepatic coccidiosis in
      rabbits.
AB  - Immunization of rabbits against hepatic coccidiosis was tried. The animals were
      immunized twice with Eimeria stiedae coproantigen in freund's adjuvant with two
      week intervals. The rabbits were challenged orally with sporulated E. stiedae
      oocysts one week post last injection. The protection was assessed by number of
      oocysts output, number of focal liver lesions, clinical sings and antibody
      response. The immunization resulted in 70% protection from infection and decline
      in oocysts count. High level of IgG response in immunized rabbits than control
      infected ones was occurred and being responsible for the recorded protection. The
      electrophoretic make up of the coproantigen and oocyst antigen showed different
      patterns of separation. Common as well as specific bands to each antigen were
      identified. Using the rabbit sera after 3 weeks post vaccination in immunoblot
      assay, immunogenic components were detected of molecular weight 155, 103, 74, 66,
      44, 22KD with coproantigen and 155, 115, 57, 26 KD with oocyst antigen. While,
      the rabbit sera after 2 and 4 weeks post challenge reacted with oocyts antigen,
      in immunoblot assay, revealing immunogenic bands of molecular weight 155, 115,
      57, 26, 22KD and 155, 115, 57, 25 KD respectively. Bands of 22KD and 155KD are
      partially responsible for eliciting host protective immune response where they
      were recognized by immunized sera in coproantigen and by immunized infected sera
      in oocyst antigen.

PMID- 16083070
TI  - Humoral and cellular immune responses induced in mice by purified iridoid mixture
      that inhibits penetration of Schistosoma mansoni cercariae upon topical treatment
      of mice tails.
AB  - When tested for possible blocking effect on the cercarial, serine proteinase,
      elastase (CE) activity, an iridoid mixture extracted from leaves of Citharexylum
      quadrangular abolished 31% of the enzyme activity at final concentration 15
      microg. When formulated in jojoba oil and applied to mice tails followed by
      infection with Schistosoma mansoni cercariae, the iridoid mixture blocked
      cercarial penetration and caused significant reducetion (94%; P < 0.05) in worm
      burden in treated mice in comparison to controls. Also, immunomodulatory effects
      of iridoid mixture, iridoid-treated S. mansoni worm homogenate on mice were
      studied by measuring IgG and IgM levels against E. coli lysates (ECL), solube S.
      mansoni worm antigenic preparation (SWAP) and cancer bladder homogenates (CBH) as
      antigens by ELISA. Cellular immune responses were studied by calculating mean
      percent of CD4+, CD8(+)-T, B-mesenteric lymph node cells (MLNC) and CD4+, CD8(+)
      T thymocytes by direct immunofluorescence staining in treated mice as compared to
      untreated homogenate given mice or untreated mice. Injecting mice with serial
      dilutions of iridoid mixture resulted in fluctuation, peaks and troughs, in both
      IgG and IgM responses against the above mentioned antigens. 1st and 2nd
      immunizations with iridoid mixture treated homogenate resulted in significantly
      elevated (P < 0.05). IgM and IgG levels against the 3 used antigens in comparison
      with sera from control mice. Immunized mice with homogenate treated with iridoid
      mixture showed a significant increase (P < 0.05) in CD4+T thymocytes, a non
      significant increase in CD8+T thymocytes, a significant increase (P < 0.05) in
      CD4+T lymphocytes (MLNC) and a non significant increase in CD8+ T- and B
      lymphocytes (MLNC) compared with mice immunized with untreated homogenate or non
      injected normal mice.

PMID- 16083071
TI  - Characterization of surface lectins binding and SDS-PAGE protein patterns of
      Biomphalaria alexandrina haemocytes infected with Schistosoma mansoni.
AB  - Seven biotinylated lectins were tested with fluorescein labeled Avidin D for
      binding to haemocyte surfaces of non-inflected and infected Biomphalaria
      alexandrina snails with Schistosoma mansoi at 24 to 72 hours post infection (PI).
      Five lectins (Con A, DBA, SBA, RCA120 and WGA) yielded positive results. Two
      lectins (PNA and UEA-I) were negative. For the five positive lectins, the use of
      specific inhibition sugar indicated presence of glucose/mannose, galactose, N
      acetyl-galactosamine (GalNAc) and N-acetyl-glucosamine (GlcNAc). The UEA-I lectin
      was negative and this indicates the absence of L-Fucose. There were no changes in
      the carbohydrates of haemocyte surfaces during the short periods (0 hr to 72 hrs)
      PI with S. mansoni. Electrophoresis of haemocyte homogenates of both non-infected
      and infected snails with S. mansoni yielded a complex pattern of polypeptides.
      The separated profiles demonstrate the occasional appearance or absence of
      certain bands in infected snails through four weeks PI. Post S. mansoni
      infection, dominant proteins appeared only through four weeks PI which were of
      average molecular masses 36, 9.3 and 5.3 kDa. At fourth week PI a remarkable
      decrease in the number of haemocyte protein fractions as well as the protein
      densities were reduced in compared to control snails. The results showed that
      qualitative and quantitative differences were detectable in the haemocyte
      proteins between non-infected and infected snails during four weeks of infection.

PMID- 16083072
TI  - The insecticidal activity of Eucalyptus globulus oil on the development of Musca
      domestica third stage larvae.
AB  - The insecticidal activity of Eucalyptus globulus oil (Camphor oil) against the
      larval maturation and adult emergency of the house-fly, Musca domestica 3rd stage
      was evaluated under controlled laboratory conditions. Concentrations of 100%,
      70%, 50% 25%, 5%, 2%, 1%, 0.9 % and 0.7% showed 100% larval mortality rate. At
      concentrations of 0.5%, 0.3%, 0.2% and 0.1% the larval mortality rate was 90%. On
      the other hand, the developed pupae did not emerge to adults. Eucalyptus globulus
      oil is safe, cheap and widely used in Medicine. So, it is recommended to be use
      in controlling larvae of M. domestica.

PMID- 16083073
TI  - Food composition and feeding habits of some fresh water fishes in various water
      systems at Abbassa, Egypt, with special reference to snails transmitting
      diseases.
AB  - Study of feeding habits of freshwater fishes collected from ponds at World Fish
      Center (ICLARM) showed that the African catfish, Clarias gariepinus and Forskal
      catfish, Bagras bayad had the highest proportion of full stomachs (31-58% & 44
      45% respectively). In cichlid fishes, the rate of full stomachs was much lower,
      being 0.0-12.5% and showed higher incidence of empty stomachs that varied from
      37.5% for Oreochromis niloticus to 78.3% for Sarotherodon galilaeus. Food items
      were analyzed by the percentage of point assessment (P%), abundance (N%) and
      frequency of occurrence (F%). Results of the three methods of analyses (Index of
      relative importance, I.R.I) emphasized the importance of plants (1214.7) as a
      major food resource in the stomach of Nile tilapia, O. niloticus followed by
      shell fragments (628.5), whereas, snail soft bodies were the main food category
      in the diet of hybrid tilapia O. niloticus x O. aureus (2539.3). Shell fragments
      (652) and snail soft bodies (296.9) were the 1st in relative importance as foods
      of O. aurea. In case of S. galillae, shell fragments (338) came 2nd in I.R.I.
      after plants (559). Present investigation shows that shell fragments were
      represented by 11.1% and 15.1% in the diet of African catfish, C. gariepinus by
      (N%) and (P%) methods, however, they came as the second food item in its diet by
      I.R.I (1237.3). According to F% method, both shell fragments and Crustacea were
      present in the diet of C. gariepinus considerable proportions each of 47.4%.
      Shell fragments were represented by low proportions in the diet of B. bayad 3.9,
      2.1 and 22.2 by N%, P% and F% respectively.

PMID- 16083074
TI  - Blastocystis hominis among symptomatic and asymptomatic individuals in Talkha
      Center, Dakahlia Governorate, Egypt.
AB  - Blastocystis hominis is now getting acceptance as an agent of human intestinal
      disease. B. hominis in stool samples of symptomatic and asymptomatic individuals
      was evaluated as a possible cause of gastro-intestinal troubles. B. hominis was
      found in 106 (10.1%) out of 1050 individuals examined from six villages and one
      city in Talkha Center, Dakahlia Governorate. The highest infection rate was in
      Manshayt El-Badawy village (25.47%), whereas Talkha City showed the lowest rate
      (4.73%). Age group 10-20 years had higher infection (13.3%). In twenty-three
      symptomatic patients, B. hominis represented the only causative parasitic agent.
      The most common symptoms were diarrhoea (30.4%), abdominal pain (26.1%),
      flatulence (21.7%). vomiting (13.1%) and fatigue (8.7%). High concentrations of
      B. hominis were found in symptomatic patients than in asymptomatic ones with
      statistical significant difference (8.2 cells/100 x field versus 3.8
      respectively). The mean number of B. hominis was significantly high in patients
      complaining of diarrhoea and abdominal pain.

PMID- 16083075
TI  - Acaricidal efficacy of Myrrh (Commiphora molmol) on the fowl tick Argas persicus
      (Acari: Argasidae).
AB  - Five concentrations of purified extract of Myrrh from Commiphora molmol tree were
      prepared to study its effects on the fowl tick Argas persicus under laboratory
      conditions. The results revealed that Myrrh had dependant dose toxic effect on
      the adult female of A. persicus. Toxicity increased gradually daily post
      treatment. The LC50 was 1.28%, 0.88%, 0.84%, 0.50% and 0.42% at Ist, 2nd, 3rd,
      6th and 12th days respectively. At 12th day, the recorded mortality rates were
      63, 67, 76, 87 and 94% for concentrations, 0.625, 1.25, 2.5, 5 and 10%,
      respectively against 5% in control. Histopathological and Transmission election
      microscope (TEM) examinations showed the lysing of epithelial gut cells in
      treated groups. The lysed epithelial gut cells showed irregularly distributed
      nucleus, commonly at low concentrations and rarely in high concentrations of
      Myrrh. The lysed epithelial gut cells, without nucleus or with aggregated one
      beside the basal lamina, were common at high concentrations and rare in low
      concentrations of Myrrh. Consequently, Myrrh can rapidly penetrate the cuticle to
      body cavity, destroy the epithelial gut cells and finally cause the death of
      ticks.

PMID- 16083076
TI  - Chemical composition and insecticidal activity of the volatile oils of leaves and
      flowers of Lantana camara L. cultivated in Egypt.
AB  - GC and GC/MS analysis of the hydrodistilled volatile oils of the leaves and
      flowers of Lantana camara L. cv. flava (Verbenaceae) cultivated in Egypt revealed
      both qualitative and quantitative variations. Experimentally, twenty-nine and
      twenty-two components were identified in the volatile oils of leaves and flowers
      representing 91.91% and 95.24% of the total composition of both oils
      respectively. The major constituents of the leaves volatile oil were
      caryophyllene <E-> (9.76%), cineol <1.8-> (9.37%) and pinene <Beta-> (8.15%). The
      flowers volatile oils were caryophyllene <E-> (18.20%), humulene <Alpha-> (12.22
      %) and bicyclegermacrene (10.33%). Comparing the chemical composition of the
      volatile oils of the leaves and flowers of L. canara cv., flava from different
      origins, seasons and even experimental conditions revealed that there are
      significant qualitative and quantitative variations. The larvicidal effect of the
      volatile oils of L. camara cv., flava leaves and flowers of was tested against
      the maturation of Musca domestica L. larvae in the laboratory at concentrations
      (0.0125%, 0.025%. 0.05%, 0.1% and 0.2%). They showed mortality rate ranged from
      80%- 100%. On the other hand, 10-20% of the developed pupae emerged to adults.
      Adults' fecundity was in larvae given a concentration of 0.0125%. In conclusion,
      the volatile oils of the leaves and flowers of L. camara cv., flava can be safely
      recommended in controlling M. domestica 3rd stage larvae.

PMID- 16083077
TI  - Molecular characterization of Egyptian Trichomonas vaginalis clinical isolates by
      HSP70 restriction fragment length polymorphism.
AB  - Molecular typing of 20 Egyptian Trichomonas vaginalis clinical isolates was
      performed using the Restriction Fragment Length Polymorphism (RFLP) analysis
      employing a probe from the heat-inducible cytoplasmic HSP70 gene family
      hybridized with EcoR l-digested genomic DNA. In each of the isolates tested 5 to
      6 distinct DNA fragments ranging from 2.7 Kb to 7.5 Kb in size were detected.
      Analysis of 13 isolates from symptomatic and 7 isolates from asymptomatic women
      revealed 6 distinct RFLP pattern subtypes of T. vaginalis. Eleven isolates (55%)
      showed the same RFLP pattern, teen of them (90.9%) were from symptomatic
      patients. T. vaginalis virus (TVV) was present in 7 isolates (35%). Only one
      isolate was considered resistant to Metronidazole. There were no relations
      between TVV infection or Metronidazole susceptibility and RFLP subtypes.

PMID- 16083078
TI  - Anti-Fasciola antibodies among rodents and sheep in Jeddah, Saudi Arabia.
AB  - A total of 20 imported sheep were examined for fascioliasis natural infection by
      kato thick smear and by Fasciola-indirect haemagglutination test (IHAT). Stool
      examination revealed infection in 13/20 (65%), but IHAT identified 11/20 (55%).
      So, the sensitivity was 84.5%. Also, five species of rodents trapped within or
      nearby the infected sheep farm by IHAT showed positive reactions of in Rattus
      rattus (22.4%), R. norvegicus (16.7%), Meriones crassus (11.8%), Juculus jaculus
      (zero%), Acomys c. dimidiatus (9.4%). The overall positive IHA reac-tion was
      11/143 or 14.7%. The presence of natural fascioliasis infection in imported sheep
      and wild rodents were discussed.

PMID- 16083079
TI  - Introduction: bioethics in court.

PMID- 16083080
TI  - Expert testimony by ethicists: what should be the norm?

PMID- 16083081
TI  - Bioethics testimony: untangling the strands and testing their reliability.

PMID- 16083082
TI  - Imwinkelried's argument for normative ethical testimony.

PMID- 16083083
TI  - Expert bioethics testimony.

PMID- 16083084
TI  - Is there any indication for ethics evidence? An argument for the admissibility of
      some expert bioethics testimony.

PMID- 16083085
TI  - The roles of ethicists in managed care litigation.

PMID- 16083086
TI  - Ethics expertise in civil litigation.

PMID- 16083087
TI  - California's Proposition 69: a dangerous precedent for criminal DNA databases.

PMID- 16083088
TI  - Dying in America--an examination of policies that deter adequate end-of-life care
      in nursing homes.

PMID- 16083089
TI  - A multidisciplinary approach to an ethic of biodefense and bioterrorism.

PMID- 16083090
TI  - Quarantines and distributive justice.

PMID- 16083091
TI  - Off with their heads: the need to criminalize some forms of scientific
      misconduct.
AB  - Improvement in policy for the management of scientific misconduct has been slow.
      While assurance of due process at the ORI level is now in place, similar
      protections at the institutional level and institutional responsibility for
      further oversight and a workplace where the responsible conduct of research can
      be practiced have not yet been addressed. In contrast, policy regarding human
      subject protection has evolved rapidly to reflect firmer norms, with decisive
      priority given to subject protection over scientific or social needs. Perhaps
      because scientific misconduct policy has the potential to harm the careers of
      individual scientists and harms to individual subjects are thought to be
      indirect, the scientific community has been successful in blocking every move
      toward testing more rigorous regulation. The mantras that scientists can
      discipline their own, and the price of competitive science is some level of
      scientific misconduct are not persuasive. The standards by which science is
      judged should not be an exception to those governing others who deal with the
      public's money and have a duty to the public interest.

PMID- 16083092
TI  - Physician-assisted suicide and criminal prosecution: are physicians at risk?

PMID- 16083093
TI  - Terri Schiavo and the Roman Catholic tradition of forgoing extraordinary means of
      care.

PMID- 16083094
TI  - Facts, lies, and videotapes: the permanent vegetative state and the sad case of
      Terri Schiavo.

PMID- 16083095
TI  - Currents in contemporary ethics.

PMID- 16083096
TI  - The ethical health lawyer.

PMID- 16083097
TI  - Recent developments in the law and ethics of embryonic research: can science
      resolve the ethical problems it creates?

PMID- 16083098
TI  - The latest face of medical review panels in Wyoming.

PMID- 16083099
TI  - Pharma's commitment to maintaining a clinical trial register: increased
      transparency or contrived public appeasement?

PMID- 16083100
TI  - U.S. Supreme Court hears oral arguments in Ashcroft v. Raich background.

PMID- 16083101
TI  - Drug companies offer major discounts to uninsured.

PMID- 16083102
TI  - A biogenic volatile organic compounds emission inventory for Yunnan Province.
AB  - The first detailed inventory for volatile organic compounds (VOC) emissions from
      vegetation over Yunnan Province, China was presented. The spatially and
      temporally resolved inventory was developed based on a geographic information
      system (GIS), remote sensing (RS) data and field measurement data, such as
      digitized land-use data, normalized difference vegetation index (NDVI) and
      temperature data from direct real-time measurement. The inventory has a spatial
      resolution of 5 km x 5 km and a time resolution of 1 h. Urban, agriculture, and
      natural land-use distributions in Yunnan Province were combined with biomass
      factors for each land-use category to produce a spatially resolved biomass
      inventory. A biogenic emission inventory was developed by combining the biomass
      inventory with hourly emission rates for tree, shrub and ground cover species of
      the study area. Correcting for environmental factors, including light intensity
      and temperature, a value of 1.1 x 10(12) gC for total annual biogenic VOC
      emissions from Yunnan Province, including 6.1 x 10(11) gC for isoprene, 2.1 x
      10(11) gC for monoterpenes, and 2.6 x 10(11) gC for OVOC was obtained. The
      highest VOC emissions occurred in the northwestern, southwestern and north region
      of Yunnan Province. Some uncertainties were also discussed in this study.

PMID- 16083103
TI  - Characterization of aliphatic hydrocarbons in deep subsurface soils near the
      outskirts of Beijing, China.
AB  - Thirty-nine deep subsurface soils (150-180 cm depth) near the outskirts of
      Beijing were investagated. The concentrations including n-alkanes from C13 to
      C36, pristane and phytane were in the range of 0.60 to 170.10 microg/g, with a
      median value of 4.26. Carbon preference index values for n-alkanes ranged from
      1.08 to 2.98, with a median value of 1.48. The percentage contribution of "wax" n
      alkanes was in the range of 6.03%--46.22%. A predominance of odd/even carbon n
      alkanes and unresolved complex mixtures with different shapes and ranges were
      frequently observed. Factor analysis reduced the data set into three principal
      components and confirming contributions from low (19.58%), medium (20.49%)
      molecular weight species and long-chain n-alkanes (43.41%), respectively.
      Molecular biomarkers such as pristane, phytane, hopanes and steranes were
      detected. Based on the principal component analysis, the concentration profiles
      and molecular markers, it was found that the aliphatic hydrocarbons were from
      both biogenic and anthropogenic sources.

PMID- 16083104
TI  - PAHs pollution from traffic sources in air of Hangzhou, China: trend and
      influencing factors.
AB  - PAHs pollution in air of arterial roads was investigated from October 1998 to
      October 2001 in Hangzhou, China. The results showed that sigma10 PAHs was 13-36
      microg/m3, among which, BaP, a strong carcinogenic kind ranged from 0.034
      microg/m3 to 0.12 microg/m3. PAHs pollutions in four seasons were winter > autumn
      > spring-summer. The annual averages of sigmaPAHs concentration were 25 microg/m3
      for 1999, 28 microg/m3 for 2000, and 29 microg/m3 for 2001, respectively. Leaded
      gasoline was banned in December 1998 in Hangzhou, thus comparative measurements
      with PAHs in leaded and lead-free gasoline powered motor exhausts made it certain
      that the use of lead-free gasoline leaded to a heavier PAHs pollution in roadside
      air from December, 1998, in China, and sigmaPAHs in air samples after the lead
      banning were more than twice of that in samples before the action. For the large
      contribution of vehicle discharge to air pollution in roadside, further research
      was performed to suggest the factors influencing PAHs distribution in vehicle
      exhaust in order to control air pollution effectively. Compared to gasoline
      engines, emissions from diesel engines were less toxic, although they might
      produce more PAHs. Of the same vehicular and oil type, automobiles of longer
      mileages produced more toxic PAHs. PAHs distributions in the vehicular exhausts
      were related to the oil type. Large difference was found in the abundance of 3-,
      5- and 6-ring PAHs between exhausts from gasoline and diesel oil engines. Diesel
      oil engines produced relative lighter PAHs such as NAPH, ACEN, FLUOR, while
      gasoline engines emitted heavier kinds such as BkF, IN and BP. The automobile
      produced more PAHs with the increase of mileage especially FLUR, PY, BaP, BP.
      Some significant ratios for traffic source in Hangzhou such as PHEN/AN, FLUR/PY,
      IN/BP were 0.50-4.3, 0.58-7.4, 0.51-1.5, respectively. A source fingerprint for
      vehicle exhausts of a mixture of vehicle and oil types in the city district for
      light-duty vehicle was the abundance of BaA, followed by NAPH, BP, IN. 4-ring
      PAHs such as FLUR, PY, BaA and CHRY were the most predominant kinds followed by 6
      ring PAHs(BP, IN).

PMID- 16083105
TI  - Methanogenesis acceleration of fresh landfilled waste by micro-aeration.
AB  - When municipal solid waste (MSW) with high content of food waste is landfilled,
      the rapid hydrolysis of food waste results in the imbalance of anaerobic
      metabolism in the landfill layer, indicated by accumulation of volatile fatty
      acids (VFA) and decrease of pH value. This occurrence could lead to long lag time
      before the initiation of methanogenesis and to the production of strong leachate.
      Simulated landfill columns with forced aeration, with natural ventilation, and
      with no aeration, were monitored regarding their organics degradation rate with
      leachate recirculation. Hydrolysis reactions produced strong leachate in the
      column with no aeration. With forced aeration, the produced VFA could be
      effectively degraded, leading to the reduction in COD of the leachate effluent
      since the week 3. The CH4 in the landfill gas from the column with aeration rate
      of 0.39 m3/(m3 x d) and frequency of twice/d, leachate recirculation rate of 12.2
      mm/d and frequency of twice/d, could amount to 40% (v/v) after only 20 weeks.
      This amount had increased up to 50% afterward even with no aeration. Most of COD
      in the recirculated leachate was removed. Using natural ventilation, CH4 could
      also be produced and the COD of the leachate effluent be reduced after 10 weeks
      of operation. However, the persistent existence of oxygen in the landfill layer
      yielded instability in methanogenesis process.

PMID- 16083106
TI  - Pilot regulation of MnP-SA for treating PTA wastewater.
AB  - In the pilot study of treating the purified terephthalic acid (PTA) wastewater
      with the functional Strain Fhhh in the carrier activated sludge process (CASP),
      the ratio of COD: TN: TP and the concentrations of Cu, Mn, Se and Zn were
      controlled to improve the manganese peroxidase (MnP) levels for increasing the
      treatment efficiency. When the ratio of COD: TN: TP was 100: 0.36: 0.15 and the
      concentrations of Cu, Mn, Se and Zn were 0.54, 5.07, 0.00 and 0.08 mg/L, the MnP
      specific activity (MnP-SA) reached 689 U/L, and the sludge loading rate to
      COD(SLRC) was 1.09 d(-l), which was 4--7 fold of that in other processes
      reported. The data indicated that improving MnP level could enhance the
      degradability of Fhhh. And the potentials of Fhhh and CASP will be also discussed
      in this paper.

PMID- 16083107
TI  - Joint toxicity of methamidophos and cadmium acting on Abelmoschus manihot.
AB  - Joint toxicity of methamidophos and cadmium (Cd) on the ornamental Abelmoschus
      manihot was firstly examined and compared with single-factor effects of the two
      pollutants using ecotoxicological indexes including the inhibitory rate of seed
      germination, root elongation and inhibitory concentration 50% (IC50). The results
      indicated that methamidophos and Cd had unobvious( p > 0.05) effects on seed
      germination of the ornamental. There were significant( p < 0.05) inhibitory
      effects of Cd on root elongation of the tested plant. When the concentration of
      added Cd was low( < 20 mg/L), significant antagonistic effects on root elongation
      were observed. And synergic effects were observed when Cd was added in high dose(
      > 20 mg/L). However, the analysis of joint effects indicated that there were
      antagonistic effects between Cd and methamidophos under all the treatments. At
      the high concentration of Cd, joint toxicity of methamidophos and Cd was more
      dependent on concentration of Cd.

PMID- 16083108
TI  - Phosphorus fractionation and bio-availability in Taihu Lake (China) sediments.
AB  - Typical sediments from Taihu Lake, a meso-to-hypereutrophic lake, were collected
      and examined on the basis of P-fractionation by sequential extraction scheme.
      Sedimentary inorganic phosphorus were fractioned into four forms and the rank
      order according to the mean concentration of P-fractions in Taihu Lake was NaOH-P
      > BD-P > HCI-P > NH4Cl-P. The concentrations of BD-P were linearly correlated
      with the content of active Fe (R2 = 0.96). Also, the linear relationship between
      the sum of BD-P and NaOH-P and the sum of active Fe and active Al content was
      observed within the six sediments investigated (R2 = 0.96). Moreover, the bio
      available phosphorus (BAP) content was estimated by the sum of NH4 Cl-P, BD-P,
      and NaOH-P, viz. BAP = NH4 Cl-P + NaOH-P + BD-P. In Taihu Lake, the BAP contents
      are ranging from 0.10 mg/g dw to 1.25 mg/g dw, and average 0.40 mg/g dw for all
      sediment samples. The relative contributions of BAP to total sedimentary
      phosphorus (TP) and inorganic sedimentary phosphorus (IP) range from 18.67% to
      50.79% (33.61% on average) and from 52.82% to 82.09% (67.81% on average),
      respectively.

PMID- 16083109
TI  - Present status and changes of the phytoplankton community after invasion of
      Neosalanx taihuensis since 1982 in a deep oligotrophic plateau lake, Lake Fuxian
      in the subtropical China.
AB  - Phytoplankton assemblages in the subtrophical oligotrophic Lake Fuxian, the
      second deepest lake in China, were investigated monthly from September 2002 to
      August 2003. A total of 113 species belonging to seven phyla were identified,
      among them, a filamentous green alga, Mougeotia sp., dominated almost throughout
      the study period and comprised most of the total phytoplankton biomass. Mougeotia
      sp. has made a substantial development during the past decades: it was absent in
      1957, only occasionally present in 1983, increased substantially in 1993, and
      became predominant in 2002-2003. It is likely that natural invasion of the Taihu
      Lake noodlefish (Neosalanx taihuensis) has led to a change of dominant
      herbivorous zooplankton from small to large calanoid, which has increased grazing
      pressure on small edible algae, and thus has indirectly favored the development
      of the inedible filamentous Mougeotia sp.

PMID- 16083110
TI  - Biological stability in drinking water: a regression analysis of influencing
      factors.
AB  - Some parameters, such as assimilable organic carbon (AOC), chloramine residual,
      water temperature, and water residence time, were measured in drinking water from
      distribution systems in a northern city of China. The measurement results
      illustrate that when chloramine residual is more than 0.3 mg/L or AOC content is
      below 50 microg/L, the biological stability of drinking water can be controlled.
      Both chloramine residual and AOC have a good relationship with Heterotrophic
      Plate Counts (HPC)(log value), the correlation coefficient was--0.64 and 0.33,
      respectively. By regression analysis of the survey data, a statistical equation
      is presented and it is concluded that disinfectant residual exerts the strongest
      influence on bacterial growth and AOC is a suitable index to assess the
      biological stability in the drinking water.

PMID- 16083111
TI  - Herbicide activity of monosulfuron and its mode of action.
AB  - Monosulfuron was developed for weed control in the field of wheat (Triticum,
      aestivum L.) and millet (Panicum miliaceum L.) with the application rate ranging
      from 15 to 60 g ai/hm2. Herbicidal activity of monosulfuron was evaluated
      systematically by bioassay using maize (Zea mays L.) taproot as indicator and
      weed fresh weight of Acalypha australis L. and Echinochloa phyllopogon. Maize CAU
      3138 was the most tolerant cultivars to monosulfuron with IC50 (concentration of
      50% inhibition) of 85 microg/kg, Yedan 13 was one of the most sensitive cultivars
      to monosulfuron with IC50 of 6.4 microg/kg. Monosulfuron inhibited the growth of
      Acalypha australis L. strongly comparing with that of Echinochloa phyllopogon.
      Monosulfuron was a good acetolactate synthase (ALS) inhibitor in vitro, the I50
      (50% of inhibition) of monosulfuron, chlorsulfuron, tribenuron-methyl and
      nicosulfuron for CAU 3138 were 32, 2, 19 and 26 nmol/L respectively, for Yedan 13
      the I50 were 15, 3, 17 and 65 nmol/L respectively. In vivo ALS inhibition
      occurred only in higher concentration of 4 sulfonylurea herbicide tested.
      Comparison study of this test indicated that the mode of action of monosulfuron
      was the same as that of other sulfonylurea herbicides such as chlorsulfuron,
      tribenuron-methyl and nicosulfuron, they were all inhibitors targeted at the ALS.

PMID- 16083112
TI  - Phosphorus removal by the multipond system sediments receiving agricultural
      drainage in a headstream watershed.
AB  - Wetland systems in headstream watersheds are important to control the nonpoint
      source pollutant phosphorus. Experiments were conducted using intact sediment
      water columns obtained from the multipond system in Liuchahe watershed of Chaohu
      Lake to determine its capacity to retain P. It was found that pond sediments had
      strong P retention ability. For the Hill pond, Village pond and Rice pond, their
      retention coefficient(A) were 288.3, 279.2 and 260.8 L/m2, respectively. The
      equilibrium P concentration (EPCw) were 0.016, 0.028 and 0.018 mg/L,
      respectively. The Hill pond indicated the highest P retention ability. P retained
      in the pond sediments indicated high stable degree. P removal from the overlying
      water column into the pond sediments followed a first-order kinetic model. Under
      the experimental hydrological conditions, the retention time had a positive
      correlation with the P loading. The multipond system could provide enough
      retention time to retain P in drainage runoffs. At the P levels evaluated, the
      sediments of the multipond system are effective sinks to retain P from nonpoint
      source runoffs.

PMID- 16083113
TI  - Effect of bio-surfactant on municipal solid waste composting process.
AB  - Bio-surfactant is a new type of surfactant that is produced in microbial
      metabolism. Adding bio-surfactant during composting process, especially to those
      contain some toxic substances, has been proved to be a promising way. In this
      study, Strains III (2), a bacterial with high activity to produce bio-surfactant,
      were isolated firstly. Following comparison experiments with and without adding
      Strains III (2), namely Run 1 and Run R, were conducted, respectively. The
      experimental results showed that, by adding Strains III (2), the surface tension
      could reduce from 46.5 mN/m to 39.8 mN/m and the corresponding time to maintain
      the surface tension under 50 mN/ m could prolong from 60 h to 90 h. The oxygen
      uptake rate and total accumulated oxygen consumption with Stains III (2) were
      both higher than those without Strains III (2), while the accumulation of H2S in
      outlet gas was reduced to around 50% of Run R. Moreover, two additional
      experiments were also carried out to examine the effects of strains coming from
      different systems. One is adding Strains III (2) with a dose of 0.4% (Run 2), and
      the other is seedling commercial Strains at the same conditions, the composting
      experiments showed that: Run 2 was more effective than Run 3, because the
      commercial Strains can be suppressed significantly in a complex composting system
      with different pH, high temperature and some of metals. The bio-surfactant was
      also added into the solid waste, which contained some toxic substances, the
      corresponding results showed that the remove rate of Hg and sodium
      pentachlorophenolate (PCP-Na) could be improved highly. Thus, the
      microenvironment, reactionrate and composting quality could be enhanced
      effectively by adding bio-surfactant to the composting process.

PMID- 16083114
TI  - Sonocatalytic degradation of methyl orange in the presence of (nanometer and
      ordinary) anatase TiO2 powders.
AB  - The nanometer and ordinary anatase titanium dioxide (TiO2) powders were adopted
      as the sonocatalysts for the degradation of methyl orange used as a model
      compound for the first time. It was found that the sonocatalytic degradation
      effect of methyl orange in the presence of TiO2 powder were much better than that
      without TiO2, but the sonocatalytic activity of the nanometer anatase TiO2
      particle was obviously higher than that of ordinary anatase TiO2 particle.
      Although there are many factors influencing sonocatalytic degradation of methyl
      orange, the experimental results showed that the best degradation ratio of methyl
      orange could be obtained when the experimental conditions were: initial
      concentration 15 mg/L, nanometer anatase TiO2 adding amount 750 mg/L, ultrasonic
      frequency 40 kHz, output power 50 W, pH = 3.0 and temperature 40 degrees C within
      150 min. In addition, the catalytic activity of reused nanometer anatase TiO2
      catalyst was also studied and found to decline gradually comparing with initial
      nanometer anatase TiO2 catalyst. All experiments indicated that the method of the
      sonocatalytic degradation of organic pollutants in the presence of TiO2 powder
      was an advisable choice for non- or low-transparent organic wastewaters.

PMID- 16083115
TI  - Stability of expanded granular sludge bed process for terylene artificial silk
      printing and dyeing wastewater treatment.
AB  - Terylene artificial silk printing and dyeing wastewater (TPD wastewater),
      containing averaged 710 mg/L terephthalic acid(TA) as the main carbon source and
      the character pollutant, was subjected to expanded granular sludge bed (EGSB)
      process. The stability of the EGSB process was firstly conducted by laboratory
      experiment. TA ionization was the predominated factor influencing the acid-base
      balance of the system. High concentration of TA in wastewater resulted in
      sufficient buffering capacity to neutralize the volatile fatty acids (VFA)
      generated from substrate degradation and provided strong base for anaerobic
      system to resist the pH decrease below 6.5. VFA and UFA caused almost no
      inhibition on the anaerobic process and biogas production except that pH was
      below 6.35 and VFA was at its maximum value. Along with the granulating of the
      activated sludge, the efficiency of organic removal and production rate of biogas
      increased gradually and became more stable. After start-up, the efficiency of COD
      removal increased to 57%-64%, pH stabilized in a range of 7.99-8.04, and
      production rate of biogas was relatively high and stable. Sludge granulating,
      suitable influent of pH and loading were responsible for the EGSB stability. The
      variation of VFA concentration only resulted in neglectable rebound of pH, and
      the inhibition from VFA could be ignored in EGSB. The EGSB reactor was stable for
      TPD wastewater treatment.

PMID- 16083116
TI  - Study of control strategy and simulation in anoxic-oxic nitrogen removal process.
AB  - The control strategy and simulation of external carbon addition were specially
      studied in an anoxic-oxic (A/O) process with low carbon: nitrogen (C/N) domestic
      wastewater. The control strategy aimed to adjust the flow rate of external carbon
      dosage to the anoxic zone, thus the concentration of nitrate plus nitrite (NOx(-)
      -N) in the anoxic zone was kept closed to the set point. The relationship was
      studied between the NOx(-) -N concentration in the anoxic zone (S(NO)) and the
      dosage of external carbon, and the results showed that the removal efficiency of
      the total nitrogen (TN) could not be largely improved by double dosage of carbon
      source when S(NO) reached about 2 mg/L. Through keeping S(NO) at the level of
      about 2 mg/L, the demand of effluent quality could be met and the carbon dosage
      could be optimized. Based on the Activated Sludge Model No. 1 (ASM No. 1), a
      simplified mathematical model of external carbon dosage was developed. Simulation
      results showed that PI controller and feed-forward PI controller both had good
      dynamic response and steady precision. And feed-forward PI controller had better
      control effects due to its consideration of influent disturbances.

PMID- 16083117
TI  - Elimination of formaldehyde over Cu-Al2O3 catalyst at room temperature.
AB  - Catalytic elimination of formaldehyde (HCHO) was investigated over Cu-Al2O3
      catalyst at room temperature. The results indicated that no oxidation of HCHO
      into CO2 occurs at room temperature, but the adsorption of HCHO occurs on the
      catalyst surface. With the increase of gas hourly space velocity (GHSV) and inlet
      HCHO concentration, the time to reach saturation was shortened proportionally.
      The results of the in situ DRIFTS, Density functional theory calculations and
      temperature programmed desorption(TPD) showed that HCHO was completely oxidized
      into HCOOH over Cu-Al2O3 at room temperature. With increasing the temperature in
      a flow of helium, HCOOH was completely decomposed into CO2 over the catalyst
      surface, and the deactivated Cu-Al2O3 is regenerated at the same time. In
      addition, although Cu had no obvious influence on the adsorption of HCHO on
      Al2O3, Cu dramatically lowered the decomposition temperature of HCOOH into CO2.
      It was shown that Cu-Al2O3 catalyst had a good ability for the removal of HCHO,
      and appeared to be promising for its application in destroying HCHO at room
      temperature.

PMID- 16083118
TI  - Degradation of H-acid in aqueous solution by microwave assisted wet air oxidation
      using Ni-loaded GAC as catalyst.
AB  - A novel process, microwave assisted catalytic wet air oxidation (MW-CWO), was
      applied for the degradation of H-acid (1-amino-8-naphthol-3, 6-disulfonic acid)
      in aqueous solution. Ni-loaded granular activated carbon (GAC), prepared by
      immersion-calcination method, was used as catalyst. The results showed that the
      MW-CWO process was very effective for the degradation of H-acid in aqueous
      solution under atmospheric pressure with 87.4% TOC (total organic carbon)
      reduction in 20 min. Ni on GAC existed in the form of NiO as specified by XRD.
      Loss of Ni was significant in the initial stage, and then remained almost
      constant after 20 min reaction. BET surface area results showed that the surface
      property of GAC after MW-CWO process was superior to that of blank GAC.

PMID- 16083119
TI  - Groundwater remediation engineering sparging using acetylene--study on the flow
      distribution of air.
AB  - Air sparging (AS) is an emerging method to remove VOCs from saturated soils and
      groundwater. Air sparging performance highly depends on the air distribution
      resulting in the aquifer. In order to study gas flow characterization, a two
      dimensional experimental chamber was designed and installed. In addition, the
      method by using acetylene as the tracer to directly image the gas distribution
      results of AS process has been put forward. Experiments were performed with
      different injected gas flow rates. The gas flow patterns were found to depend
      significantly on the injected gas flow rate, and the characterization of gas flow
      distributions in porous media was very different from the acetylene tracing
      study. Lower and higher gas flow rates generally yield more irregular in shape
      and less effective gas distributions.

PMID- 16083120
TI  - Screening on oil-decomposing microorganisms and application in organic waste
      treatment machine.
AB  - As an oil-decomposable mixture of two bacteria strains (Bacillus sp. and
      Pseudomonas sp.), Y3 was isolated after 50 d domestication under the condition
      that oil was used as the limited carbon source. The decomposing rate by Y3 was
      higher than that by each separate individual strain, indicating a synergistic
      effect of the two bacteria. Under the conditions that T = 25-40 degrees C, pH = 6
      8, HRT (Hydraulic retention time) = 36 h and the oil concentration at 0.1%, Y3
      yielded the highest decomposing rate of 95.7%. Y3 was also applied in an organic
      waste treatment machine and a certain rate of activated bacteria was put into the
      stuffing. A series of tests including humidity, pH, temperature, C/N rate and oil
      percentage of the stuffing were carried out to check the efficacy of oil
      decomposition. Results showed that the oil content of the stuffing with inoculums
      was only half of that of the control. Furthermore, the bacteria were also
      beneficial to maintain the stability of the machine operating. Therefore, the
      bacteria mixture as well as the machines in this study could be very useful for
      waste treatment.

PMID- 16083121
TI  - Mechanism of NO reduction with non-thermal plasma.
AB  - Non-thermal plasma has been proved to be an effective and competitive technology
      for removing NO in flue gas since 1970. In this paper, the NO reduction mechanism
      of the non-thermal plasma reaction in NO/N2/O2 system was investigated using the
      method of spectral analysis and quantum chemistry. By the establishment of NO
      reduction and gas discharge plasma emission spectrum measuring system, the NO
      reduction results, gas discharge emission spectra of NO/N2/O2 and pure N2 were
      obtained, and then the model of molecular orbit of N2 either in ground state or
      its excited state was worked out using the method of molecular orbit Ab initio in
      Self-Consistent Field (SCF). It was found that NO reduction in NO/N2 gas
      discharge plasma was achieved mainly through a series of fast elementary
      reactions and the N(E6) at excited state was the base for NO reduction.

PMID- 16083122
TI  - Microbial activity related to N cycling in the rhizosphere of maize stressed by
      heavy metals.
AB  - A greenhouse experiment was carried out to compare differences in potential
      activities of ammonification, nitrification and denitrification in rhizosphere
      and bulk soil in a heavy-metal-stressed system. Exchangeable fractions of Cd, Cu
      and Cr were all higher in the rhizosphere of maize than in bulk soil. Results
      showed that the mineralization of N in soil was stimulated by low concentration
      of Cd. Addition of Cd at low levels stimulated the ammonifying and nitrifying
      activity in soil, while inhibitory influences were shown at high levels.
      Nitrifying bacteria was proved to be the most sensitive one, whilst the effect on
      denitrifying bacteria was very limited. Comparing Cd, Cu and Cr(VI) at 20 mg/kg
      soil, Cd was the most effective inhibitor of ammonification and denitrification,
      while Cr(VI) had the strongest inhibitory influence on nitrifying activity. Root
      exudates played important roles on the different exchangeable metal fractions and
      bacterial activities between rhizosphere and non-rhizosphere. Nitrate was the
      main form of mineral N in soil, as well as the main form of N absorbed by plants,
      but the formation and relative absorption of ammonium were promoted in response
      to high Cd exposure.

PMID- 16083123
TI  - Subcellular localization of copper in tolerant and non-tolerant plant.
AB  - The ability of Elsholtzia splendens Naki (E. splendens) to accumulate copper
      appears to be governed by its high degree of coppertolerance. However, the
      tolerance mechanism on the physiological basis is unknown. Using transmission
      electron microscope (TEM) and energy dispersive analysis of X-rays (EDX), the
      likely location of copper within the cells of the tolerant and non-tolerant was
      determined. Here the role of vacuolar and cell wall compartmentalization in this
      copper tolerant plant were investigated. A direct comparison of copper locations
      of E. splendens and the non-tolerant Astragalus sinicus L. (A. sinicus) showed
      that the majority of copper in the tolerant was localized primarily in the
      vacuolar, cell wall, on the plasmamembrane, beside lipid grains induced by copper
      pollution, in the chloroplasts and amyloids; but in the non-tolerant, copper
      precipitates only be observed on the plasmamembrane, in the chloroplasts and
      cytoplasm under copper exposure conditions that were toxic to both species. This
      revealed that the tolerant accumulates more copper in the vacuole and cell wall
      than the non-tolerant, where was regarded as the storage compartment of tolerant
      plant or hyperaccumulator for heavy metals.

PMID- 16083124
TI  - Automatic control strategy for step feed anoxic/aerobic biological nitrogen
      removal process.
AB  - Control of sludge age and mixed liquid suspended solids concentration in the
      activated sludge process is critical for ensuring effective wastewater treatment.
      A nonlinear dynamic model for a step-feed activated sludge process was developed
      in this study. The system is based on the control of the sludge age and mixed
      liquor suspended solids in the aerator of last stage by adjusting the sludge
      recycle and wastage flow rates respectively. The simulation results showed that
      the sludge age remained nearly constant at a value of 16 d in the variation of
      the influent characteristics. The mixed liquor suspended solids in the aerator of
      last stage were also maintained to a desired value of 2500 g/m3 by adjusting
      wastage flow rates.

PMID- 16083125
TI  - Contamination of soil, leaves and vegetables by polychlorinated biphenyls in
      Xiamen region, China.
AB  - The paper aimed to identify the primary of polychlorinated biphenyls(PCBs) in the
      Jiulong River Estuary, investigate the spatial distribution of PCBs contamination
      in the environment, localize the atmospheric source and evaluate ongoing PCBs
      emissions by analyzing soil samples collected along the Jiulong River region. In
      addition, the accumulation of PCBs in the human food chain was quantified by
      analyzing leaf of orange trees and vegetable samples collected along a gradient
      of soil/atmospheric contamination moving away from the source. Consequently, the
      impact on the human health and the ecosystem was quantified, different management
      options were proposed to reduce this impact and to carry out research on organic
      contaminants along the Jiulong River and Xiamen region.

PMID- 16083126
TI  - Gas-initiation under UV and liquid-grafting polymerization on the surface of
      polysulfone hollow fiber ultrafiltration membrane by dynamic method.
AB  - Using the inner-surface of polysulfone hollow fiber ultrafiltration membranes as
      grafted layer, the method of gas-initiation and liquid-polymerization has been
      studied, which aimed to adjust the diameter of the pores in the membranes. The
      degree of polymerization varied with the changes of the parameters, such as
      irradiation time, monomer concentration, temperature and time of polymerization
      and soon. The results indicated that using benzophenone (BP) which is in a
      gaseous condition as photo-initiator, acrylamide as graft monomer, the
      polyacrylamide chain was grafted on the surface of membranes. After the surface
      membrane being modified, the water flux and retention altered, and thus it can be
      seen that the diameter of the pores in the membrane was altered. These
      experiments contribute to finding a new way to produce the hollow fiber membrane
      with the small pore size and are extraordinarily worth developing and studying.

PMID- 16083127
TI  - Effect of methylmercury on some neurotransmitters and oxidative damage of rats.
AB  - In order to study the molecular mechanism of injury in rat organs induced by
      methylmercury, and the relationship between neurotransmitter and oxidative damage
      in the toxicity process of rat injury by methylmercury was studied. The control
      group was physiological saline of 0.9%, the concentration of exposure groups were
      5 mg/( kg x d) and 10 mg/( kg x d) respectively. The content of AChE, ACh, NOS,
      NO, MDA, SOD, GSH-Px and GSH in different organs of rats were determined with
      conventional methods. The results showed that after exposure to methylmercury for
      7 d, the mercury content in brain of exposure groups increased clearly and had
      significant difference compared with the control group (P < 0.01). In rat's
      brain, serum, liver and kidney, the content of ACh and AChE were all decreased;
      the content of NOS and NO were all increased; the content of MDA was increased
      compared with the control group, the exposure groups had significant difference
      (P < 0.01); the content of SOD, GSH and GSH-Px was decreased compared with the
      control group, the exposure groups had significant difference (P < 0.01). It
      could be concluded that methylmercury did effect the change of neurotransmitter
      and free radical. They participated in the toxicity process of injury by
      methylmercury. The damage of neurotransmitter maybe cause the chaos of free
      radical and the chaos of free radical may also do more damage to neurotransmitter
      vice versa.

PMID- 16083128
TI  - Municipal sludge as landfill barrier material.
AB  - The aim of this research is to find substitute barrier materials for natural clay
      from two kinds of municipal sludge: waterworks sludge (S(W)) and dredging sludge
      (Sd). Laboratory tests were performed firstly to determine their Atterberg limits
      and hydraulic conductivity. Based on the results, the use of waterworks sludge
      was recommended. Then, shear strength tests were performed and it was found the
      shear resistance property of waterworks sludge is strong enough to maintain slope
      stability. In order to evaluate the possibility of secondary pollution, the heavy
      metal contents of waterworks sludge was determined and the results indicated that
      secondary pollution is unlikely happened. Finally, economic analysis proves that
      reusing waterworks sludge as barrier will reduce the lost a great for both
      landfill and waterworks. Based on the results, waterworks sludge was proposed to
      use and a further long-term simulated landfill test was suggested.

PMID- 16083129
TI  - Sorption of dissolved organic matter and its effects on the atrazine sorption on
      soils.
AB  - The dissolved organic matter (DOM), water soluble organic matter derived from
      sewage sludge was separated into hydrophobic fraction (Ho) and hydrophilic
      fraction (Hi). The sorption of DOM and its fractions on soils and the effects of
      DOM sorption on a nonionic pesticide (atrazine(2-chloro-4-ethylamino-6
      isopropylamino-1,3,5-trazine)) distribution between soil and water were
      investigated using a batch equilibrium technique. The total DOM sorption on soils
      described by the Langmuir equation reached saturation as the DOM concentration
      increased. The sorption of Ho fit the Freundlich model. In contrast, a negative
      retention evidently occurred as adding Hi at higher level in tested soils. The
      sorption of Ho dominated the total DOM sorption and the release of soil organic
      matter (SOM). Effects of DOM on the atrazine sorption by soils were DOM
      concentration dependent and dominated by the interaction of atrazine, DOM, and
      soil solids. Generally, the presence of DOM with lower concentration promoted
      atrazine sorption on soils, namely the apparent partitioning constant (Kd) for
      atrazine sorption in the presence of DOM was larger than the distribution
      constant (Kd) without DOM; whereas the presence of DOM with higher concentration
      inhibited atrazine sorption (i.e., Kd < Kd). The overall effects of DOM on
      atrazine sorption in soils might be related to the DOM sorption and the release
      of soil intrinsic organic matter into aqueous solution. The sorption of Ho on
      soils promoted the atrazine sorption on soil, while the release of SOM by Hi and
      the competitive sorption between Hi and atrazine on soil surface led to a
      decrease of atrazine sorption. Information provided in this work may contribute
      to a better understanding of the DOM sorption and its impacts on the contaminant
      soil-water distribution.

PMID- 16083130
TI  - Effect of inhibitors on macroscopical oxidation kinetics of calcium sulfite.
AB  - In the presence of inhibitors, the macroscopical oxidation kinetics of calcium
      sulfite, the main byproduct in wet limestone scrubbing, was studied for the first
      time by adding different inhibitors and varying pH, concentration of calcium
      sulfite, oxygen partial pressure, concentration of inhibitors and temperature.
      The mathematical model about the general oxidation reaction was established,
      which was controlled by three steps involving dissolution of calcium sulfite,
      mass transfer of oxygen and chemical reaction in the solution. It was concluded
      that the general reaction was controlled by mass transfer of oxygen under
      uncatalyzed conditions, while it was controlled by dissolution of calcium sulfite
      after adding three kinds of inhibitors. Thus, the theory was provided for
      investigating the mechanism and oxidation kinetics of sulfite. The beneficial
      references were also supplied for design of oxidation technics in the wet
      limestone scrubbing.

PMID- 16083131
TI  - Study on the wind field and pollutant dispersion in street canyons using a stable
      numerical method.
AB  - A stable finite element method for the time dependent Navier-Stokes equations was
      used for studying the wind flow and pollutant dispersion within street canyons. A
      three-step fractional method was used to solve the velocity field and the
      pressure field separately from the governing equations. The Streamline Upwind
      Petrov-Galerkin (SUPG) method was used to get stable numerical results. Numerical
      oscillation was minimized and satisfactory results can be obtained for flows at
      high Reynolds numbers. Simulating the flow over a square cylinder within a wide
      range of Reynolds numbers validates the wind field model. The Strouhal numbers
      obtained from the numerical simulation had a good agreement with those obtained
      from experiment. The wind field model developed in the present study is applied
      to simulate more complex flow phenomena in street canyons with two different
      building configurations. The results indicated that the flow at rooftop of
      buildings might not be assumed parallel to the ground as some numerical modelers
      did. A counter-clockwise rotating vortex may be found in street canyons with an
      inflow from the left to right. In addition, increasing building height can
      increase velocity fluctuations in the street canyon under certain circumstances,
      which facilitate pollutant dispersion. At high Reynolds numbers, the flow regimes
      in street canyons do not change with inflow velocity.

PMID- 16083132
TI  - Residue analysis and dissipation of a new fungicide 2-allylphenol in tomato.
AB  - The method of residue analysis of a new synthesized fungicide 2-allylphenol was
      studied by simulating the active compound structure in Gingko tree (Gingko biloba
      L.) and its dissipation rate and terminal residue levels in tomato under field
      condition. Residues of 2-allylphenol were extracted from tomato matrix with
      acetone, purified by liquid-liquid extraction and Florisil cartrieges, and then
      determined by HPLC with UV-detector. The minimum detectable amount of 2
      allylphenol was 3 x 10(-9) g, the minimum detectable concentration of 2
      allylphenol in the samples of tomato were 0.01 mg/kg. The ranges of average
      recoveries and coefficient variation of the method were 87.7%-90.2% and 1.25%
      2.06%, respectively. The dissipation rate and terminal residue levels in tomato
      were determined with the method described above. The results showed that the half
      life of 2-allylphenol in tomato was 6.37 d, and 2-allylphenol declined with 82.6%
      of the initial deposit remaining in tomato at harvest. The terminal residue
      levels in tomato were 0.15 mg/kg and 0.20 mg/kg following the recommended doses
      and time intervals.

PMID- 16083133
TI  - Screening of flocculant-producing strains by NTG mutagenesis.
AB  - Screening of new microorganism being able to produce efficiently flocculants was
      carried out. A new model for screening efficient flocculant-producing strains was
      designed and tested. The results showed that this model for screening efficient
      flocculant-producing strains is very reliable and can greatly shorten the
      screening period. 13 flocculant-producing strains were isolated from activated
      sludge by conventional method. A strain, designated as HHE6, produced the
      bioflocculant with the turbidity removal 98% for kaolin suspension. Six of 13
      strains selected as the original strains were treated with NTG as mutagen, and
      five mutant strains (HHE-P7, HHE-A8, HHE-P21, HHE-P24, HHE-A26) with high
      flocculation efficiency was obtained by selection, which exhibited the
      flocculation rate for kaolin suspension above 90%. Strains HHE6, HHE-P7, and HHE
      P24 were classified as Penicillium purpurogenum, HHE-P21 as Penicillium
      cyclopium, HHE-A26 as Aspergillus versicolor and HHE-A8 as Aspergillus fumigatus,
      and it is hitherto unreported for biofloccutant-producing strains of Penicillium.
      The growth of the six strains (HHE6, HHE-P7, HHE-A8, HHE-P21, HHE-P24, HHE-A26)
      had similar curves, i.e. firstly increasing rapidly, keeping relatively constant
      then and finally decreasing gradually with cultivation time. The production of
      bioflocculants by strains showed the similar pattern to strain growth.

PMID- 16083134
TI  - Effects of exogenous Ca2+ on the membrane permeability, MDA and SH group content
      of Alexandrium sp. LC3 under surfactant stress.
AB  - The effect of Ca2+ on the removal of Alexandrium sp. LC3 under HDTMAB stress was
      investigated. The results showed that the toxic effect of HDTMAB on Alexandrium
      sp. LC3 was significantly reduced in the presence of Ca2 , especially under 4
      mmol/L of Ca2+. To understand the underlying mechanism, the SH group and MDA
      content of the cell membrane and membrane permeability were measured. It was
      found that the SH content of cell member increased, the MDA content and membrane
      permeability decreased when Alexandrium sp. was treated with Ca2+ and HDTMAB
      complex, compared with using HDTMAB only. The data suggested that Ca2+ might
      promote HDTMAB stress resistance of Alexandrium sp. LC3 by reducing the
      permeability and increasing the stability of cell membrane.

PMID- 16083135
TI  - Dissipation of chlorpyrifos on pakchoi inside and outside greenhouse.
AB  - The dissipation of chlorpyrifos on pakchoi inside and outside greenhouse was
      studied. The decline curve of chlorpyrifos on pakchoi could be described as first
      order kinetic. The experimental data showed that both the hermetic environment of
      greenhouse and season affected dissipation rates of chlorpyrifos on pakchoi.
      Chlorpyrifos declined faster outside greenhouse than inside greenhouse.
      Chlorpyrifos residues at pre-harvest time were below the maximum residue limits
      (MRLs) fixed in China, whereas the values inside greenhouse were higher than
      those outside greenhouse by almost 50%. The recommended pre-harvest time
      established under conditions of open field might not always fit to greenhouse
      production.

PMID- 16083136
TI  - Cultivation and characters of aerobic granules for pentachlorophenol (PCP)
      degradation under microaerobic condition.
AB  - Cultivation of aerobic granular sludge for pentachlorophenol (PCP) degradation
      under microaerobic condition (DO concentration was controlled at 0.2-0.7 mg/L)
      was studied in this paper. Anaerobic granules were selected as inoculum. The
      changes of appearance were observed and the variations of SVI, VSS/TSS, PN/PS and
      the size of sludge were measured during cultivating. The capabilities for
      degradation of PCP, AOX and COD(Cr) were also studied. Observations on mature
      granules were carried out by scanning electron microscope, and the results
      indicated bacillus was dominant on the surface of granules while in the inner of
      granules both bacillus and coccus were the dominant microorganisms. K, Na, Fe,
      Ca, Mg, Ni, Co, Mn, Cu and Zn were detected in the granules by element analysis.

PMID- 16083137
TI  - Physico-chemical indices of breeding sites of Simulium damnosum in the lower
      Cross River Basin, Nigeria.
AB  - To determine the factor influencing the abundance development and distribution of
      Simulium damnosum (S.I) immature stages in the lower Cross River Basin, Nigeria,
      the physico-chemical characteristics of water at breeding sites were analysed
      longitudinally over a 12 month period. Analysis of the water samples showed that
      water current correlated positively and significantly (p < 0.05), with dissolved
      oxygen (r = 0.95 vs 0.10); conductivity (r = 0.95 vs 0.81); hydrogen ion
      concentration (r = 0.03 vs 0.46); and biochemical oxygen demand (r = 0.80 vs
      0.64); from Agbokim Waterfalls and Afi River respectively. The result indicates
      that these parameters and low ionic concentration are the most essential
      requirement for the development of S. damnosum pre-imaginal stages. Amplitudes of
      annual variability as measured by co-efficient of variation varied between the
      parameters. From the trends in hydrological variables it was deduced that the
      integrated impact of precipitation, input of surface runoff and municipal
      effluents played an overriding role in determining the absolute levels and
      temporal pattern in the water quality attributes. Of the 3578 pre-imaginal stages
      of S. damnosum collected, 52.52% and 47.4% were collected from Agbokim Waterfall
      and Afi River respectively. There was a significant difference (p < 0.05) in the
      number of pre-imaginal stages collected from both sites. The highest number of
      pre-imaginal stages of S. damnosum collected were at the peak of rain (July
      September) indicating that S. damnosum in the River Basin is a wet season
      breeder. The need for long term laboratory colonization of blackfly immature
      stages becomes imperative especially how these parameters could be exploited in
      control programme through the testing of larvicides without adverse ecological
      damage to the aquatic habitat.

PMID- 16083138
TI  - Vapor-phase elemental mercury adsorption by residual carbon separated from fly
      ash.
AB  - The adsorption capacity for vapor-phase elemental mercury (Hg0) of residual
      carbon separated from fly ash was studied in an attempt for the control of
      elemental mercury emissions from combustion processes. At low mercury
      concentrations (< 200 microg/m3), unburned carbon had higher adsorption capacity
      than commercial activated carbon. The adsorbality of unburned carbon was also
      found to be source dependent. Isotherms of FS carbon (separated from fly ash of a
      power plant of Shishi in Fujian Province) were similar to those classified as
      type II. Isotherms of XJ carbon (separated from fly ash of a power plant of
      Jingcheng in Shanxi Province) were more like those classified as type II. Due to
      the relatively low production costs, these residual carbons would likely be
      considerably more cost-effective for the full-scale removal of mercury from
      combustion flue gases than other technology.

PMID- 16083139
TI  - Element cycling in the dominant plant community in the Alpine tundra zone of
      Changbai Mountains, China.
AB  - Element cycling in the dominant plant communities including Rh. aureum, Rh.
      redowskianum and Vaccinium uliginosum in the Alpine tundra zone of Changbai
      Mountains in northeast China was studied. The results indicate that the amount of
      elements from litter decomposition was less than that of the plant uptake from
      soil, but that from plant uptake was higher than that in soil with mineralization
      process released. On the other hand, in the open system including precipitation
      input and soil leaching output, because of great number of elements from
      precipitation into the open system, the element cycling(except N, P) in the
      Alpine tundra ecosystem was in a dynamic balance. In this study, it was also
      found that different organ of plants had significant difference in accumulating
      elements. Ca, Mg, P and N were accumulated more obviously in leaves, while Fe was
      in roots. The degree of concentration of elements in different tissues of the
      same organ of the plants also was different, a higher concentration of Ca, Mg, P
      and N in mesophyll than in nerve but Fe was in a reversed order. The phenomenon
      indicates (1) a variety of biochemical functions of different elements, (2) the
      elements in mesophyll were with a shorter turnover period than those in nerve or
      fibre, but higher utilization rate for plant. Therefore, this study implies the
      significance of keeping element dynamic balance in the alpine tundra ecosystem of
      Changbai Mountains.

PMID- 16083140
TI  - A comparative study of classical and biochemical endpoints for phytotoxicity
      testing of chlorobenzoic acids.
AB  - The phytotoxicity of chlorobenzoic acids (CBAs) was studied and the biochemical
      endpoints' suitability and sensibility was evaluated. Two terrestrial plant
      species in the same family were exposed to different concentrations of CBAS and
      tested their germination according to the guideline of Organization for Economic
      Cooperation and Development (OECP, 1984). The results showed that CBA dose
      inhibition rate of classical endpoint had the distinct linear relationship in the
      range of 10%-50% inhibition rate for root elongation (p < 0.01), and the dose
      variances of CBAs had the greater influence on the inhibition rate of germination
      than on inhibition rate of root elongation. The CBA dose half effect
      concentration-inhibition rate of two antioxidant enzyme activity superoxide
      dismutase (SOD) and catalase (CAT) had the quadratic relationship, and CBA dose
      inhibition rate of the peroxides (POD) activity had the linear relationship (p <
      0.05). Comparing the half effect concentration (EC50) of two kinds of endpoints,
      the POD activity was more sensitive than classical endpoint, however, SOD and CAT
      activity were not sensitive in the experiment.

PMID- 16083141
TI  - Vestibular symptoms and signs are correlated with abnormal neurogenic vestibular
      evoked potentials in patients with multiple sclerosis.
AB  - OBJECTIVES: Symptoms of disequilibrium in multiple sclerosis (MS) are common.
      Neurogenic vestibular evoked potentials (NVsEPs) are saccular responses to tone
      pip acoustic stimuli and are recordable from the parietal areas ipsilaterally to
      the stimulated ear. We wished to determine possible correlations of abnormal
      findings in NVsEP with clinical neurological findings related to the vestibular
      system, and demyelination seen on MRI. PATIENTS AND METHODS: NVsEPs were
      performed by delivering a 1 kHz tone-pip stimulus monoaurally with contralateral
      masking noise via headphones. Brainstem auditory evoked potentials were performed
      in the standard manner. RESULTS: Thirty-three patients had either been diagnosed
      with MS or had possible MS. There is statistical evidence that the presence of
      symptoms is likely to give an abnormal NVsEP, but no correlation exists between
      the presence or absence of vestibular symptoms and signs and an abnormal BAEP. No
      correlation was found between the presence of brainstem lesions on MRI and an
      abnormal NVsEP. Correlation exists between abnormal NVsEP and the level of
      disability using Expanded Disability Status Scale scores. CONCLUSION: We have
      found that with increasing involvement of abnormal NVsEPs, there is a significant
      correlation with symptoms and signs that can be referred to the vestibular
      system.

PMID- 16083142
TI  - Somatosensory evoked blink response in hemifacial spasm and peripheral facial
      palsy.
AB  - Somatosensory blink response (SBR) is produced by electrical stimulation of
      peripheral nerves or skin areas remote from the face. We investigated the
      presence of SBR in cases with hemifacial spasm (HFS) and peripheral facial palsy
      (PFP). Fifty-seven cases of HFS, 54 cases of PFP and 39 normal subjects were
      included in the study. A routine blink reflex study was performed in all
      subjects. Supramaximal stimulation of the median nerve was given ipsilateral to
      the either spasm or paralytic side for SBR. Recordings were made at the
      orbicularis oculi (o.oc) bilaterally and ipsilaterally at the orbicularis oris
      (o.or) muscles. SBR was elicited in 12 of 39 control subject. Twenty four of 48
      HFS cases were SBR positive. Twelve of them had o.or response. An SBR was
      elicited at the ipsilateral o.oc in 35 of 46 patients with PFP with synkinesia.
      Twenty-six patients had an SBR at the ipsilateral o.or. In the 13 patients with
      PFP without synkinesia only 3 people had an SBR. SBR positivity was seen more
      often in PFP with synkinesia than in cases with HFS. SBR if positive spreads to
      the lower part of the face in most of cases with HFS and PFP with synkinesia.

PMID- 16083143
TI  - Usefulness of a comprehensive neurophysiological assessment for early diagnosis
      and prognosis of traumatic brachial plexus injuries.
AB  - PURPOSE: To illustrate how a thorough neurophysiological evaluation allows early
      diagnosis and prognosis of traumatic brachial plexus injuries. METHODS: As
      examples, we report on the case of two patients with acute traumatic brachial
      plexus injuries for whom a comprehensive neurophysiological evaluation allowed
      early diagnosis and prognosis. RESULTS: Neurophysiological findings were
      consistent with complete proximal (root) lesion in one patient and a severe
      neuroapraxic block between Erb point and axilla in the other one. CONCLUSIONS:
      The two reported acute cases of traumatic brachial plexus injuries demonstrated
      the high diagnostic and prognostic value of the neurophysiological tests when
      fully utilized.

PMID- 16083144
TI  - Mononeuropathy of the suprascapular nerve: study of 3 South American cases.
AB  - In this work 3 new cases of suprascapular nerve mononeuropathy are described.
      ENMG diagnosis criteria were: a) normal sensory conduction studies of the
      ipsolateral ulnar, median and radial nerves; b) bilateral suprascapular nerve
      latencies with bilateral compound muscle action potential, obtained from the
      infraspinatus muscle with symmetrical techniques; and c) abnormal neurogenic
      infraspinatus muscle electromyographic findings, coexisting with normal
      electromyographical data of the ipsolateral deltoideus and supraspinatus muscles.
      These 3 cases of suprascapular mononeurpathy were found in 6,080 ENMG exams from
      our University Hospital. For us this mononeuropathy is rare with a 0.05%
      occurrence.

PMID- 16083145
TI  - The effect of carpal tunnel release on median nerve flattening and nerve
      conduction.
AB  - Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and
      extensive surveys have been given on the time course of electrophysiological
      findings pre- and postoperatively. In patients with clinical and
      electrophysiological confirmed diagnosis of CTS surgical decompression of the
      carpal tunnel is a first line treatment and has proven to be successfull in 70 to
      90% of all cases. The objective of this work was to study the morphological
      changes of the median nerve after endoscopic release of the carpal tunnel. We
      used high resolution ultrasound to quantify flattening of the median nerve and to
      calculate a flattening ratio before endoscopic release as well as 2 weeks and 3
      months postoperatively. Ten patients with clinical and electrophysiological
      confirmed CTS were included in the study. There was significant normalization of
      the calculated flattening ratio of the median nerve already 2 weeks after
      surgical release, whereas nerve conduction studies needed a longer period of time
      to normalize and thus were still abnormal 3 months postoperatively. We conclude
      that ultrasound is a simple and excellent objective method for visualizing the
      morphological recovery of the median nerve very early after decompression
      surgery. In complex cases with unsatisfactory outcome ultrasonography may prove
      useful in confirming successfull or failed decompression of the median nerve.

PMID- 16083146
TI  - Inching method in compression neuropathy of the sural nerve distal to the ankle.
AB  - We present the case of a 29-year-old electric engineer with compression
      neuropathy of the left sural nerve due to occupational boots. Routine nerve
      conduction study of the sural nerve was normal. However, the sensory nerve action
      potential was not detected more than 3 cm distal to the lateral malleolus,
      although it returned to normal values after three years. Inching method of the
      sural nerve may be necessary for detecting compression sural neuropathy distal to
      the ankle.

PMID- 16083147
TI  - Lateral asymmetry of motor unit number estimate (MUNE).
AB  - The aspects of lateral asymmetry of the peripheral nervous system have been
      investigated to a lesser extent than the aspects of lateral asymmetry in the
      central nervous system. We utilized a statistical method of quantitative MUNE to
      demonstrate lateral asymmetry of the motor units in healthy individuals,
      revealing higher values in the nondominant hand. Awareness of this phenomenon
      will improve the accuracy and reliability of this MUNE method when used in
      clinical trials.

PMID- 16083148
TI  - Early peripheral nerve abnormalities in impaired glucose tolerance.
AB  - Increased prevalence of impaired glucose tolerance (IGT) has been recently
      detected in patients with painful sensory neuropathy. To determine whether nerve
      abnormalities are present in IGT we investigated IGT subjects without clinical
      neuropathy. Nerve conduction studies (NCS) were performed in 12 subjects with IGT
      without symptoms and signs of neuropathy. The results were compared with those
      obtained from 12 patients with type 2 diabetes (DM) without clinical neuropathy
      and 12 healthy controls. Sensory NCS of the sural nerve were performed on
      different segments, the distal-leg (10 cm proximal to the lateral malleolus) and
      the proximal-leg segment (10 cm more proximal). The distal conduction velocity of
      the sural nerve was increased in IGT subjects, compared both to healthy controls
      and DM patients. No difference was found among the groups with respect to the
      sensory conduction velocity of the sural nerve fibers in the proximal-leg
      segment. A reduction of both distal and proximal amplitudes of the sural nerve
      action potentials was detected in DM patients compared with IGT subjects and
      controls. The abnormal conduction velocity in the distal segment of the sural
      nerve, observed in IGT subjects without clinical neuropathy, suggests that the
      myelin dysfunction of the distal sensory fibers represents the earliest
      detectable nerve response to the hyperglycemia. The reduced amplitude of the
      sural nerve action potential in asymptomatic patients with DM arises from the
      axonal degeneration and represents a more advanced stage of nerve disease.

PMID- 16083149
TI  - A new method using F-waves to measure muscle fiber conduction velocity (MFCV).
AB  - OBJECTIVE: First, to propose a new technique for measuring muscle fiber
      conduction velocity (MFCV). Second, to ascertain the validation of the new method
      that uses F-waves (F-MFCV) in healthy volunteers. Third, to examine the
      relationship between F-MFCV and motor nerve conduction velocity (MCV) in the same
      subjects. SUBJECTS AND METHODS: F-waves reflecting single motor units were
      recorded with a multi-channel surface electrode array and weak electrical
      stimulation to the median or ulnar nerves in 21 healthy volunteers. F-MFCVs of
      the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) were
      calculated from the F-wave peak latency in each channel. MFCV during minimal
      voluntary contraction (V-MFVC) was measured in the same muscles. RESULTS: There
      was no significant difference between F-MFCV and V-MFCV in the muscles tested The
      mean F-MFCV value was similar to recently reported MFCV values generated by
      minimal voluntary contraction. No significant differences were found between the
      APB and ADM F-MFCVs, whereas the MCV of the ulnar nerve was faster than that of
      the median nerve. CONCLUSION: The MFCV in a single motor unit could be measured
      with a multi-channel surface electrode array by recording F-waves induced by weak
      stimulation. Since V-MFCV generated by minimal voluntary contraction is explained
      by the size principle, V-MFCV reflects small and slow conducting motor unit.
      There was no significant difference between F-MFCV and V-MFCV. It seemed that F
      MFCV also reflected small motor unit. The reason for the lack of difference in
      the F-MFCVs of the ADM and APB is considered to be a relatively slow F-MFCV.
      Moreover, MCV reflected the speed of the fastest nerve fiber, whereas F-MFCV did
      not.

PMID- 16083150
TI  - History of King Chulalongkorn Memorial Hospital: 90 years anniversary.
AB  - The Thai Red Cross Society was founded by King Rama V (King Chulalongkorn) in
      1893 (B.E. 2436) after an international conflict with France. The institute was
      originally called Saphaa Unaalom Daeng which was later named the Red Cross
      Society of Siam and did not get its permanent headquarters until 1914 in the
      reign of King Rama VI (King Vajiravudh) when Chulalongkorn Memorial Hospital was
      founded. It was the mandate of King Rama VI that the hospital is to be "most
      elegant, popular and marveled with the most modern medical equipments,..." the
      best hospital of the Orient, in order to be the most glorified memorial for King
      Chulalongkorn, the Father of King Rama VI. The hospital has been the leader in
      medical services, public health as well as medical science, and home to the
      Faculty of Medicine, Chulalongkorn University which has been the center of
      medical research at national and international levels.

PMID- 16083151
TI  - Serum estradiol level in Thai surgical menopausal women receiving oral micronized
      17 beta-estradiol 1mg.
AB  - OBJECTIVE: To compare serum estradiol (E2) level in Thai surgical menopausal
      women before and after receiving a daily dose of 1 mg oral micronized 17 beta
      estradiol. DESIGN: Experimental study (before and after treatment). SETTING:
      Gynecological ward, Hatyai regional hospital. PATIENTS: 40 premenopausal Thai
      women who had undergone total abdominal hysterectomy with bilateral
      salpingoooporectomy (Surgical menopause) for 1 week previously due to benign
      gynecologic conditions were recruited in the present study. These women had no
      contraindications for receiving hormonal replacement therapy and no history of
      any hormonal intake in the past. INTERVENTION: All women were assigned to receive
      a 1 mg micronized 17 beta-estradiol (Estrofem, Novo Nordisk A/S, Denmark) orally
      applied at bedtime (08.00 p.m.) each day. MEASUREMENTS: Serum estradiol (E2)
      levels were measured before and after treatment at 4, 8 and 12 weeks. The
      hormonal measurement was performed using the ELFA-technique (Enzyme Linked
      Fluorescent Assay). RESULTS: Four cases were excluded due to loss to follow up.
      Of the remaining 36 cases, the mean age (+/- SD) and the body mass index were
      46.27 +/- 5. 74 years and 23.72 +/- 2.92 kg/m2, respectively. Serum E2 level
      significantly increased from baseline value at 4, 8 and 12 weeks (mean (+/- SD)
      of E2 level at 0, 4, 8 and 12 weeks: 3.82 +/- 6.30 pg/ml, 117.11 +/- 92.86 pg/ml,
      135.28 +/- 91.38 pg/ml and 164.48 +/- 78.94 pg/ml, p < 0.05) respectively.
      CONCLUSION: A daily dose of 1 mg oral micronized 17 beta-estradiolfor 12 weeks
      increased the serum E2 level to the follicular phase level of the normal
      menstrual cycle.

PMID- 16083152
TI  - Outcome of colorectal liver metastases.
AB  - OBJECTIVE: To determine the median survival of colorectal liver metastatic (CRLM)
      patients treated at King Chulalongkorn Memorial Hospital over the past 10 years
      and to determine the outcome of the various treatment modalities (surgery,
      chemotherapy and supportive treatment). MATERIAL AND METHOD: Between January,
      1992 and December, 2001, 86 consecutive patients were recorded. Of whom 26
      (30.23%) received liver resection, 39 (45.34%) received chemotherapy and 21
      (24.41%) received supportive treatment. All the patients were followed up to
      December 31, 2001 or death. Survival was calculated by Kaplan-Meier method and
      studied for statistical differences between various treatment groups with Cox
      regression model. The 95% confidence intervals for median assessment were
      determined. RESULTS: Overall survival of CRLM patients was 18 months. Significant
      differences in survival were seen among the three groups of patients. Median
      survival was 33 months in the liver resection group, 17 months in the
      chemotherapy group and 5 months in the supportive treatment group. Three-year
      survival in the liver resection group was 23% while it was 7.6% in the
      chemotherapy group. Type of treatment, primary tumor staging and extrahepatic
      metastasis were the three independent determinant factors of survival.
      CONCLUSION: Survival of patients with colorectal liver metastases depends on the
      type of treatment. Liver resection is the best treatment which offers long term
      survival to the patients in selected cases.

PMID- 16083153
TI  - Endoscopic transaxillary thyroid lobectomy: flexible vs rigid laparoscope.
AB  - BACKGROUND: The use of the endoscopic procedure for thyroid lobectomy in benign
      solitary thyroid nodule has been developed rapidly and increasingly refined in
      recent years. The early results are technically feasible, safe and mainly provide
      promising cosmetic results, some show a quicker recovery. The authors wanted to
      know if this procedure can be performed via rigid laparoscope which is simple,
      less expensive and widely available in many surgical centers. OBJECTIVES: The
      aims of this study were to evaluate operative time, blood loss, complication of
      flexible compared to 30 degrees rigid laparoscope in endoscopic transaxillary
      thyroid lobectomy for solitary thyroid nodule. METHOD: From February 2004 to June
      2004, 13 cases of benign solitary thyroid nodule underwent the endoscopic
      transaxillary thyroid lobectomy. Flexible laparoscope techniques were performed
      in 9 cases and 30 degrees rigid laparoscope in the other 4 cases. Port site,
      number of ports and dissected method were the same in both procedures by the same
      surgeon. Operative time, blood loss, post-operative results were measured for
      evaluation. RESULTS: From 13 cases, 9 in the flexible laparoscope group and 4 in
      the rigid laparoscope group. All but one in the flexible group with torn internal
      jugular vein were successful. The mean operation time was 165.42 +/- 35.06
      minutes, which was 175.63 +/- 35.70 minutes for flexible laparoscope group and
      145 +/- 26.45 minutes for rigid laparoscope group. There was no recurrent
      laryngeal nerve injury and no subcutaneous emphysema. The patients were satisfied
      with the cosmetic results. CONCLUSION: On the basis of early experience with
      these 13 patients, the authors believe that endoscopic thyroidectomy using the
      rigid laparoscope has proved to be no different in the intra-operative results,
      so the authors do aimed to show that with the rigid laparoscope which is
      available in many surgical centers, less expensive and easy in maintenance will
      provide another surgical option for treatment of thyroid nodule, with maximized
      cosmetic effect.

PMID- 16083154
TI  - Lidocaine iontophoresis versus EMLA cream for CO2 laser treatment in seborrheic
      keratosis.
AB  - BACKGROUND: Topical anesthesia for skin surgery has widely been used for a long
      time. Various preparations are used. The EMLA cream is the most popular one.
      OBJECTIVE: The authors compared the local analgesic effect of topical lidocaine
      iontophoresis and EMLA cream in a crossover study design. METHOD: After informed
      consent, 16 patients with seborrheic keratosis, who required CO2 laser surgery,
      were enrolled. Two lesions on the opposite side of the body with a comparable
      size, shape and location were selected from each patient. The lidocaine
      iontophoresis was done on one lesion and the EMLA cream was applied on the other
      The CO2 laser surgery was performed after 10 min of lidocaine iontophoresis and
      60 min after EMLA cream. The level of pain was recorded using a 100-mm visual
      analog scale. Ratings of patient satisfaction were also assessed. RESULTS: There
      were no significant differences in pain scores between the two groups (p=0.968),
      but significantly higher in satisfaction scores (1-5 scale) in the iontophoretic
      group than the EMLA group (p=0.005). Fifteen patients preferred lidocaine
      iontophoresis (93.8%), none preferred EMLA cream. All patients in the present
      study tolerated the tingling and burning sensations. No severe adverse events and
      side effects were detected. CONCLUSION: Lidocaine iontophoresis provides
      effective pain relief for CO2 laser surgery of seborrheic keratosis as well as
      the EMLA cream. The effect is as fast as 10 min after application. There is no
      significant side effect. Most of the patients were satisfied. Lidocaine
      iontophoresis is a useful, noninvasive local anesthesia for CO2 laser surgery of
      superficial skin lesions.

PMID- 16083155
TI  - A more appropriate algorithm of thyroid function test in diagnosis of
      hyperthyroidism for Thai patients.
AB  - BACKGROUND: Thyroid function test is an essential tool in the diagnosis of
      thyroid dysfunction. To date, it is still controversial which diagnostic
      algorithm is best applicable to clinically hyperthyroidism patients. OBJECTIVE:
      To compare various algorithms of thyroid function tests in the diagnosis of
      hyperthyroidism. METHOD: Patients from the endocrine clinic, King Chulalongkorn
      Memorial Hospital were investigated for thyroid function tests (T3, T4, FT3, FT4
      and TSH). Hyperthyroidism was defined as an elevated either FT3 or FT4 with
      suppressed TSH. The authors compared the effectiveness in hyperthyroidism
      diagnosis among algorithms by using sensitivity, specificity, positive predictive
      value and negative predictive value. RESULTS: Of all 452 patients in the present
      study, 94.24 percent were women. There were 206 hyperthyroidism, 30 subclinical
      hyperthyroidism, 1 subclinical hypothyroidism, 8 primary hypothyroidism and 207
      normal subjects. The incidence of T3 toxicosis was 16.02% while that of T4
      toxicosis was 2.16%. After the effectiveness analysis of these algorithms, FT3
      and TSH is the most optimal test with 97.57% sensitivity and 100% specificity.
      Compared to FT4 and TSH, it gave 83.98% sensitivity and 100% specificity.
      CONCLUSION: According to the high incidence of T3 toxicosis in the present study,
      FT3 and TSH should be the initial test for diagnosis of hyperthyroid patients in
      an outpatient setting and FT4 should be measured subsequently in case of
      suspected T4 toxicosis.

PMID- 16083156
TI  - Causes of idiopathic constipation in Thai patients: associations between the
      causes and constipation symptoms as defined in the Rome II criteria.
AB  - The authors investigated 103 consecutive Thai patients (29M, 74F age 50 +/- 20)
      with chronic idiopathic constipation (symptom duration; median 5 yr, range 0.25
      45 yr) as defined by Rome II criteria using colonic transit test, anorectal
      manometry, and balloon expulsion tests. Constipation symptoms were evaluated by a
      questionnaire. RESULTS: There were 30, 14, 11, and 48 patients who fulfilled the
      criteria of anorectal dysfunction, colonic inertia, anorectal dysfunction plus
      colonic inertia, and the normal transit constipation, respectively. The
      proportion of female gender in the normal transit constipation group (F:M=37:11)
      was significantly greater than the anorectal dysfunction group (16.14, p<0.05%).
      Patients with colonic inertia and colonic inertia plus anorectal dysfunction had
      a higher prevalence of infrequent bowel movement compaired to anorectal
      dysfunction and normal transit constipation (p<0.001). The prevalence of
      straining, hard stool, incomplete evacuation, sense of anal obstruction, and use
      of manual maneuver to facilitate defecation, were not different among the
      constipation subgroups (p>0.05). CONCLUSIONS: Prevalence of pathophysiologic
      conditions associated with idiopathic constipation in Thai patients are similar
      to Western countries. 29%, 13%, and 11% of Thai patients with idiopathic
      constipation were associated with anorectal dysfunction, colonic inertia, and
      anorectal dysfunction plus colonic inertia, respectively. Among the 6
      constipation symptoms defined by Rome II criteria, only infrequent bowel
      movements was associated with delayed colonic transit.

PMID- 16083157
TI  - The prevalence of nonalcoholic steatohepatitis in Thai patients with non-HBV, non
      HCV chronic hepatitis.
AB  - This study aimed to determine the prevalence of nonalcoholic steatohepatitis in
      Thai patients with non-HBV, non-HCVchronic hepatitis. The clinical and laboratory
      findings associated with non alcoholic steatohepatitis were discussed. Forty-six
      patients with negative markers for viral hepatitis B and viral hepatitis C and no
      history of alcohol consumption or consumption less than 20 grams of ethanol per
      day were recruited. The informed consent for liver biopsy and blood collecting to
      identify the etiology of chronic hepatitis was performed. Most patients (76.1%)
      exhibited fatty metamorphosis of the liver which included steatosis (21.8%) as
      well as steatohepatitis (54.3%). Eleven of 46 patients (23.9%) were classified as
      cryptogenic chronic hepatitis. There were statistically significant differences
      between the fatty metamorphosis group and the cryptogenic chronic hepatitis group
      with regard to the fasting blood sugar, serum alkaline phosphatase, serum
      ferritin and histologically necroinflammatory grading score (p < 0.05). Between
      the steatosis group and the steatohe-patitis group, body mass index (BMI) was the
      only factor showing statistically significant difference (p = 0.02). Eight from
      25 NASH-patients had diabetes mellitus (32.0%) and the AST to ALT ratio in this
      group was 0.6. The histopathological assessment for inflammation and fibrosis by
      using Knodell score, the fibrosis score which equal or higher than 3 was found in
      20.0% of NASH-patients. CONCLUSION: The prevalence of NASH-patients in Thai
      patients, with non HBV, non HCV chronic hepatitis was 76.1%, while the liver
      biopsy can add the diagnostic yield especially in the group of unexplained
      chronic hepatitis with obesity, diabetes mellitus and dyslipidemia.

PMID- 16083158
TI  - Result of wireless capsule endoscopy in patients with suspected small bowel
      disease: the first series from Thailand.
AB  - BACKGROUND AND AIMS: Capsule endoscopy (CE) is a promising diagnostic tool for
      patients with obscure gastrointestinal bleeding. Only a few papers have reported
      data from Asian countries. This retrospective study aimed to demonstrate result
      of capsule endoscopy in patients with suspected small bowel disease as the first
      series from Thailand. METHOD: Twenty-one patients who underwent wireless capsule
      endoscopy between July 2003 and June 2004 at King Chulalongkorn Memorial Hospital
      were retrospectively reviewed in the present study. The indications for capsule
      endoscopy were overt obscure gastro-intestinal bleeding (n= 12), occult obscure
      gastro-intestinal bleeding (n=5), chronic recurrent abdominal pain (n=3) and
      chronic diarrhea (n=1). Diagnoses according to findings of capsule endoscopy were
      classifield into definite, suspicious and negative finding. RESULTS: The mean age
      of the 21 patients (10 men and 11 women) was 46 (standard deviation, 18.57)
      years. Of those 17 obscure gastrointestinal bleeding patients, there were
      positive findings in 11 from 17 patients (65%). Four patients (24%), 3 with tumor
      and another with AVM, were classified as definite results. Seven patients (41%),
      6 with angioectasia and another with a small ulcer, were classified as suspicious
      because there was no demonstrated active bleeding lesion and no other clinical
      supportive evidence. Of these 3 patients with recurrent abdominal pain, one
      patient (33%) with terminal ileum lymphoid hyperplasia was classified as definite
      result because of clinical improvement after treatment of the lesion. Another
      case of chronic diarrhea yielded a negative result. CONCLUSION: Wireless capsule
      endoscopy is a safe and useful mode of investigation for the diagnosis of obscure
      gastrointestinal bleeding in Thailand. There is not so much difference in capsule
      endoscopy results between Western and Asian series.

PMID- 16083159
TI  - Clinical manifestations of patients with hyperuricemia.
AB  - OBJECTIVE: To study the clinical manifestations of patients with hyperuricemia in
      King Chulalongkorn Memorial Hospital. METHOD: A cross sectional study of 188
      hyperuricemic patients was done at King Chulalongkorn Memorial Hospital. History,
      physical examination, and blood samples were drawn to assess complete blood count
      (CBC), blood urea nitrogen (BUN), creatinine (Cr), liver function test (LFT), and
      serum uric acid in all patients. RESULTS: Most of the patients (92%) were male,
      more than 50 years old (69%), the mean age of the patients was 56.7 +/- 12.1
      years old. All of the female patients were more than 50 years old. Symptomatic
      hyperuricemia was found in 93%, the mean duration of symptoms was 63.2 +/- 66.3
      months. The mean of the serum uric acid level was 10.0 +/- 2.9 mg/dl. Associated
      diseases were found in 46% of the patients, and 30% of these patients had more
      than one disease. Hypertension was the most common followed infrequency by
      dyslipidemia, diabetes mellitus, ischemic heart disease, and chronic obstructive
      pulmonary disease consecutively. Renal impairment was detected in about one-third
      of the patients. CONCLUSION: This study shows that hyperuricemia is common in
      elderly, male patients. Associated diseases and renal impairment can
      befoundfrequently, and the patients should be monitored.

PMID- 16083160
TI  - Validity of tidal breathing flow volume loops in diagnosing obstructive sleep
      apnea in young children with adenotonsillar hypertrophy: a preliminary study.
AB  - Tidal breathing flow volume loops (TBFVL) can indicate the site/severity of upper
      airway obstruction (UAO). The authors did a pilot study to determine 1) the
      correlation between TBFVL and obstructive sleep apnea (OSA) as well as its
      severity and 2) the validity of TBFVL in determining OSA and desaturation during
      sleep in young children with a denotonsillar hypertrophy (ATH). A cross sectional
      analytical study was performed in 10 patients with ATH (age 4.2 +/- 0.4 yrs; 40%
      female) at King Chulalongkorn Memorial Hospital during January-June 2004. All had
      polysomnography and TBFVL performed during sleep. Median apnea/hypopnea index
      (AHI) was 3.4/hr. Eight (80%) patients had OSA. The TBFVL was normal in 2,
      variable UAO in 3, and fixed UAO in 5 patients. Among these 3 groups, the number
      of OSA patients (2, 3 and 3, respectively; ns) and the number of those who had
      desaturation (2, 3 and 3, respectively; ns) were not different. There was no
      correlation between mid tidal expiratory flow rate/mid tidal inspiratory flow
      rate (Me/Mi) ratio and AHI (r=0.5; ns) or lowest arterial oxygen saturation
      during sleep (r=-0.4; ns). The accuracy of Me/Mi > 1.5 for diagnosing OSA and
      desaturation was 50% and 60%, respectively. The abnormal TBFVL also had the same
      accuracy in defining these 2 conditions. In conclusion, TBFVL did not correlate
      with OSA and its severity and had low accuracy in determining either OSA or
      desaturation in young children with ATH.

PMID- 16083161
TI  - Epidemiology and clinical manifestation of rotavirus and norwalk-like viruses in
      Thai children.
AB  - Acute gastroenteritis is one of the most common diseases affecting children and
      rotavirus is the major etiological agent worldwide. Although the role of
      rotavirus as a causal agent of gastroenteritis has been previously established in
      Thailand, little is known about the epidemiology of Norwalk-like viruses. The
      present study was designed to determine the epidemiology and clinical
      manifestation of Norwalk-like viruses in comparison with rotavirus in Thailand.
      One hundred and one children with watery diarrhea between November 2002 and
      October 2003 were recruited into the study. The clinical data and stool specimens
      were collected for clinical analysis and rotavirus and Norwalk-like virus
      detection. Rotavirus and Norwalk-like viruses were detected viral agent by RT-PCR
      method. Of 101 stool samples obtained, rotavirus was detected in 25/101 (24.7%).
      Norwalk-like viruses were detected in 23/101 (22.7%). Dual infections were
      detected in 6/101 (5.9%). Rotavirus and Norwalk-like viruses peaked in the winter
      time. Clinical manifestations of rotavirus and Norwalk-like viruses were watery
      stool, nausea, vomiting, abdominal pain and fever Norwalk-like viruses and
      rotavirus were the most common etiologic agents in children with acute
      gastroenteritis in Thailand Epidemiology and clinical manifestations of rotavirus
      and Norwalk-like viruses were not different.

PMID- 16083162
TI  - Muscle disorders in pediatric patients in King Chulalongkorn Memorial Hospital.
AB  - The authors retrospectively studied histopathologic findings and diagnoses of
      muscle specimens taken from 188 pediatric patients presenting with clinical
      neuromuscular disorders in King Chulalongkorn Memorial Hospital between August
      1991 and December 2003. Eighty patients (67.8%) established the definite
      diagnosis by histopathological findings of muscle specimens. About 18.6, 17.7,
      7.6, 5.9, 5.0, 3.4, 2.5 and 1.7 percent of the total number of patients were
      diagnosed as Duchenne muscular dystrophy, spinal muscular atrophy, congenital
      myopathies, mitochondrial disease, inflammatory myopathies, Becker muscular
      dystrophy, congenital muscular dystrophy and vacuolar myopathies respectively.
      Since the histopathological findings in muscle helped to establish the definite
      diagnosis in most pediatric patients in the present study, thus muscle biopsy is
      essential for establishing a definite diagnosis in any patient with a suspected
      neuromuscular disorder.

PMID- 16083163
TI  - Hospital-based epidemiology of childhood cholera: a 6-year review in a university
      hospital in Bangkok, Thailand.
AB  - BACKGROUND: Cholera is the cause of severe acute watery diarrhea. Without proper
      fluid therapy, severe cholera kills half of the affected patients. In terms of
      epidemiology and surveillance, up-to-date information of this disease in each
      country is essential. OBJECTIVES: To evaluate 1) prevalence, serogroups,
      serotypes and antimicrobial susceptibility pattern of V cholerae, and 2)
      demographic data and clinical manifestation of pediatric patients with cholera.
      MATERIAL AND METHOD: Microbiogical records of children aged 0-15 years with
      cholera, who were treated at King Chulalongkorn Memorial Hospital, Bangkok,
      Thailand, between January 1995 and December 2000 were retrospectively reviewed
      Serogroups, serotypes, and antimicrobial susceptibility of V. cholerae were
      studied Medical records of children with positive stool cultures for V. cholerae
      were reviewed in terms of demographic data, clinical manifestation of the
      patients. RESULTS: Of 11,709 stool culture specimens, pathogenic bacteria were
      found in 1,745 specimens and 95 specimens (5.4%) were positive for V. cholerae.
      V. cholerae O1 and non-O1/non-O139 were found in 52.6% and 47.4%, respectively.
      Common serotypes of V. cholorae O1 were Ogawa. Antimicrobial susceptibility of
      the pathogens to co-trimoxazole, ampicillin, ceftriaxone, ciprofloxacin and
      gentamicin were 55.0%, 56.4%, 91.4%, 92.5% and 94.9%, respectively. Age
      distribution of the patients ranged from 2 months to 15 years with an average age
      of 2.92 years. Clinical manifestations included acute watery diarrhea (92.8%),
      vomiting (56.4%), fever (37.5%), hypotension (19.6%) and abdominal pain (3.8%).
      Stool leukocytes were microscopically detected in 20% of the patients. No
      patients died in the present study. CONCLUSION: Childhood cholera in Thailand
      still exists. Most patients presented with acute watery diarrhea. Regarding
      antimicrobial susceptibility pattern, ceftriaxone and quinolones are appropriate
      drugs of choice.

PMID- 16083164
TI  - Umbilical cord blood transplantation in children with beta-thalassemia diseases.
AB  - To evaluate factors affecting the outcome of sibling and unrelated donor
      umbilical cord blood transplantation (CBT) in Thai children with beta-thalassemia
      diseases. The case-series study of all children undergoing such transplants in
      our institute was conducted Six children with thalassemia major were diagnosed at
      a median age of 1.5 years and CBT was performed at a median age of 5.5 years
      (range 2-15). Six donors consisted of three HLA-identical siblings, one two
      allele, one three-antigen mismatched sibling, and one one-allele mismatched
      unrelated cord blood. The median number of nucleated cells infused was 2.83 x
      10(7)/kg (range 1.49-5.3); the median number of CD34+ cells infused was 1.94 x
      10(5)/kg (range 0.2-5.3). In all, two patients had complete donor engraftment;
      three had mixed chimerism (MC); one patient died of cerebral thrombosis and
      neutropenic septicemia. Of the two complete donor-engrafted patients, two
      developed grade 2 acute graft-versus-host disease (GVHD) which responded well to
      immunosuppressive therapy. Of the three mixed-chimeric patients, two were
      clinically cured. With a median follow-up of 7 months (range 2-30), five children
      survived and have done well with transfusion-independent. Umbilical cord blood
      provides a reasonable option for hematopoietic stem cell source to transplant for
      beta-thalassemia diseases and the outcome in the present study was good.

PMID- 16083165
TI  - Comparative study of 2% ketoconazole cream and 1% hydrocortisone cream in the
      treatment of infantile seborrheic dermatitis.
AB  - OBJECTIVE: To compare efficacy of 2% ketoconazole cream with 1% hydrocortisone
      cream in the treatment of infantile seborrheic dermatitis (ISD). This study
      recruited infants of 2 weeks to 2 years old with a clinical diagnosis of
      infantile seborrheic at the Department of Pediatrics, King Chulalongkorn Memorial
      Hospital from December 2001 to November 2003. METHOD: The severity of the rash of
      the patients was examined in terms of erythema, scale and crust before treatment
      based on a scoring system comparing two sides (left and right) of the lesion with
      numeral representation for it a severity, namely: Ofor no lesion; 1, mild; 2,
      moderate; and 3, severe. They were treated with 2% ketoconazole cream on the left
      side of the lesion and 1% hydrocortisone cream on the right side of the lesion,
      twice a day. RESULTS: The responses of treatment of 2% ketoconazole cream
      compared with 1% hydrocortisone cream in 48 patients had no statistical
      significant difference at 2-3 days of treatment and 4-7 days of treatment. By one
      week, both 2% ketoconazole cream and 1% hydrocortisone cream have significant
      clinical improvement of the lesion. The skin lesions were cleared in 31% of the
      ketoconazole group and 35% of the hydrocortisone group. All skin lesions were
      cleared by the end of the second week. CONCLUSION: The efficacy of 2%
      ketoconazole cream and 1% hydrocortisone cream in the treatment of ISD was not
      significantly different. Ketoconazole is another option for the treatment of ISD,
      to avoid the side effects of topical corticosteroid in long-term use and on large
      surface area of treatment.

PMID- 16083166
TI  - Nephrocalcinosis in very low birth weight infants: a single center experience.
AB  - OBJECTIVES: To determine the incidence and risk factors of nephrocalcinosis in
      very low birth weight infants. MATERIAL AND METHOD: Medical records of inborn
      infants with gestational age less than 32 weeks or birth weight less than 1,250
      grams were collected and analyzed. All infants were born at King Chulalongkorn
      Memorial Hospital in the year 2003. At least one renal ultrasonographic scan was
      performed on every infant as a routine screening before discharge. Data on family
      history of renal stone, gestational age, birthweight, infant's illness,fluid
      intake during the first 6 weeks of life, duration of respiratory support,
      medications, serum calcium, phosphate and alkaline phosphatase level, duration of
      parenteral nutrition, length of hospitalization, ultrasonographic findings and
      related renal morbidity were collected and compared between the groups of infants
      with and without nephrocalcinosis. RESULTS: Thirty six infants were included in
      the present study. Fourteen had abnormal ultrasound scans compatible with
      nephrocalcinosis giving an overall incidence of 38.9%. Factors associated with
      nephrocalcinosis included severity of respiratory illness, PDA, oxygen
      dependency, furosemide therapy, and fluid restriction. Urinary tract infection
      was the renal morbidity found in 3 infants (21.4%). Nephrocalcinosis was resolved
      in one out of 7 infants who had repeated renal ultrasound scan at about 2 months
      after the first scan. CONCLUSION: Very low birth weight, preterm infants have a
      risk of developing nephrocalcinosis especially those with severe respiratory
      illness and prolonged use of furosemide. Infants at risk should be screened with
      renal ultrasonography prior to discharge from the hospital.

PMID- 16083167
TI  - Treatment of subfoveal choroidal neovascularization secondary to age related
      macular degeneration with single treatment of verteporfin photodynamic therapy: a
      safety and short-term outcome.
AB  - OBJECTIVE: To evaluate the short-term efficacy on visual outcome and safety of a
      single treatment of photodynamic therapy with verteporfin using the standard
      dosage regimen in patients with predominantly classic subfoveal choroidal
      neovascularization (CNV) from age related macular degeneration. DESIGN:
      Prospective, noncomparative, consecutive, interventional case series. SETTING:
      Department of Ophthalmology, Chulalongkorn University and Hospital, Bangkok,
      Thailand. PARTICIPANTS: Patients with subfoveal CNV caused by age related macular
      degeneration. METHOD: Standardized protocol refraction, visual acuity testing,
      complete ophthalmic examination, color photography, and fluorescein angiography
      were used to evaluate the effects of a single treatment of photodynamic therapy
      with verteporfin. Follow-up was planned through 3 months in all patients.
      RESULTS: A total of 39 eyes from 35 patients enrolled into the present study and
      have completed 3 months follow-up. The mean +/- SD logMAR BCVA at baseline was
      0.76 +/- 0.48, equivalent to the Snellen BCVA of 20/114 (range, 20/40 to
      20/1000). The mean +/- SD logMAR BCVA at the final 3-month visit was 0.55 +/-
      0.37, which was a Snellen equivalent of 20/70 (range, 20/30 to 20/1000). The mean
      line of BCVA improvement was 2.1 lines. The improvement in BCVA at the 3-month
      follow-up was statistically significant (Wilcoxon signed-rank test, P = .043). No
      patient suffered moderate loss of vision or a loss of vision in 2 or more lines.
      None of the patients suffered severe visual threatening adverse events at the
      time of treatment and during the study period. CONCLUSIONS: The results of short
      term visual outcome is encouraging; PDT is the least invasive treatment method
      currently available to achieve a stable or improved vision in AMD patients. PDT
      with verteporfin can lead to cessation of fluorescein leakage from CNV for up to
      3 months, with stabilization or improvement of vision for 12 weeks. A randomized,
      controlled study in the near future would be beneficial to demonstrate the long
      term results and efficacy in the treatment of CNV associated with AMD.

PMID- 16083168
TI  - Clinical evaluation of ophthalmic lomefloxacin 0.3% in comparison with fortified
      cefazolin and gentamicin ophthalmic solutions in the treatment of presumed
      bacterial keratitis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of 0.3% lomefloxacin single agent
      solution, by comparing to a combination of fortified ophthalmic solutions of
      cefazolin sodium 50 mg/ml and gentamicin sulfate 14 mg/ml, in the treatment of
      acute bacterial keratitis. DESIGN: Prospective, double-masked, randomized
      comparative trial. METHOD: Forty patients with clinical diagnosis of any grade of
      severity of acute bacterial keratitis were randomized into 2 treatment groups: 20
      to fortified cefazolin-gentamicin group, and 20 to lomefloxacin-normal saline
      group. The dosing of the drugs were scheduled for both treatment groups as
      follows: 1 drop of each solution was alternately instilled every 5 minutes for
      the first 30 minutes (as loading dose), then 1 drop with 5-minute interval
      between 2 bottles instilled hourly for day 1-3, tapering to every 2 hours on day
      4-6, and every 4 hours on day 7-14. After day 14, dosing discretion was
      clinically adjusted, based on the clinical condition and finally discontinued
      after complete healing. Corneal scraping for cultures was obtained before
      starting the treatment. Ocular symptoms and signs, time to heal and adverse
      reactions were evaluated and compared between the 2 groups on day 2, 4, 7, 14, 21
      and 28. RESULTS: No clinically or statistically significant difference were noted
      between two treatment groups, regarding demographic, symptoms and signs
      associated with bacterial keratitis. Positive results of bacterial corneal
      cultures were obtained in 27.5%. There was no statistically significant
      difference in time to complete re-epithelialization in all types of bacterial
      keratitis (P=0.251). By day 7, the keratitis was healed: 44% in lomefloxacin
      group, and 33% in fortified antibiotic group. Both study medications were well
      tolerated, with no incidence of reported adverse event. CONCLUSION: In this
      study, eventhough there is no statistically significant difference of symptoms
      and signs between the two study groups at any study visit, we found clinical
      improvement in all patients in lomefloxacin group. So, lomefloxacin may be used
      as an alternative to standard treatment in acute bacterial keratitis.

PMID- 16083169
TI  - Results of temperature-controlled radiofrequency tissue volume reduction for the
      turbinate hypertrophy.
AB  - OBJECTIVES: To assess the efficacy of temperature-controlled radiofrequency
      tissue volume reduction (RFTVR) for the inferior turbinate. RESEARCH DESIGNS:
      Prospective, single-blinded, experimental clinical trial. METHOD: Twenty patients
      with nasal obstruction secondary to inferior turbinate hypertrophy were enrolled.
      Nasal obstruction was compared between before and after the treatment (at 1-3
      days, 1 week and 6-8 weeks) of RFTVR using subjective symptom scores, physical
      findings and videotape images. RESULTS: Improvement of nasal symptoms was
      observed as early as 1 week after the operation. However, significant improvement
      was obtained at 6-8 weeks. CONCLUSION: RFTVR for the turbinate may be useful as
      an alternative approach for the treatment of chronic turbinate hypertrophy.

PMID- 16083170
TI  - The pectoralis major myocutaneous flap: applications and complications in head
      and neck reconstruction.
AB  - Ninety-six pectoralis major myocutaneous flaps were used in the head and neck
      reconstruction of 93 patients who underwent extirpation of cancer. The
      utilization of the pectoralis major myocutaneous flap included 50 tongue
      replacements, 19 hypopharynx and pharyngoesophageal closure, 11 oral mucosal
      closure and external skin replacement, 7 soft tissue coverage of the
      reconstruction plate, 3 soft tissue protection of the great vessels at the neck
      and 6 correction of the wound breakdown from failure of the other flap
      reconstruction. The major complication, which included total flap loss, partial
      skin paddle loss, orocutaneous fistula, dehiscence and plate exposure, was 17.7%.
      The overall complication rate was 54.2% and most of them were healed by
      conservative management. The pectoralis major myocutaneous flap is feasible and
      reliable for immediate reconstruction of various defects in the head and neck
      area. The pectoralis major myocutaneous flap should be the suitable flap for the
      advanced-staged cancer patient with a limited life expectancy.

PMID- 16083171
TI  - Effect of ultrasound thermotherapy in mild to moderate carpal tunnel syndrome.
AB  - OBJECTIVE: To investigate the efficacy of low intensity ultrasound thermotherapy,
      a conservative option of treatment of mild to moderate carpal tunnel syndrome
      (CTS). DESIGN: Prospective experimental, placebo- controlled, before-after
      treatment trial. SETTING: King Chulalongkorn Memorial Hospital, Outpatient Clinic
      and Electrodiagnostic Laboratory, Department of Rehabilitation Medicine.
      PATIENTS: Eighteen women, 30 hands who had clinical and electrophysiologic
      evidence of mild to moderate CTS. INTERVENTIONS: Patients of CTS were divided
      into two groups; A and B of 15 hands by random sampling. Group A was given
      placebo and continuous ultrasound therapy with the intensity of 0.5 W/cm2 applied
      to the palmar carpal tunnel for 10 minutes. Group B was given Diclofenac 75
      mg/day in divided doses and sham ultrasound. The ultrasound was applied 5 days a
      week for 4 weeks. OUTCOME MEASURES: Each patient was clinically and
      electrophysiologically evaluated before and after treatment. RESULTS: There were
      statistically significant improvements (p < 0.05), in the clinical parameters of
      both groups after treatment. In the electrophysiologic study, the median SNAP
      amplitude was increased significantly after the treatment in ultrasound group
      (group A). When both groups were compared, group A had significant difference in
      increasing of median SNAP amplitude after treatment. CONCLUSION: The therapeutic
      efficacy of low intensity ultrasound thermotherapy was satisfied for mild to
      moderate CTS. However, the electrophysiological changes after ultrasound
      treatment need further investigation.

PMID- 16083172
TI  - Effect of partial body weight support treadmill training in chronic stroke
      patients.
AB  - OBJECTIVE: To compare the effect of Partial Body Weight Support Treadmill
      Training (PBWSTT) technique and floor walking training, on floor walking
      velocities and functional balance in chronic stroke patients. DESIGN: An observer
      blinded, randomized controlled trial. MATERIAL AND METHOD: Forty-eight chronic
      stroke patients were randomized into either the experimental group that received
      PB WSTT (n=24) or the control group that received floor walking training (n=24).
      Both groups received 25 minutes of daily walking training 5 days per weeks,
      totally 4 weeks. Treatment outcomes were assessed on floor walking velocities and
      functional balance by Berg Balance Scale RESULTS: There was no statistically
      significant difference between both groups after a 4-week training period with
      regard to floor walking velocities and functional balance at p < 0.05. Patients
      in both groups had statistically significant improvement in these variables after
      a 4-week training period when compared to before training at p < 0.05.
      CONCLUSION: The efficacy of PBWSTT in chronic stroke patients was not
      statistically different to the efficacy of floor walking training in floor
      walking velocities and functional balance.

PMID- 16083173
TI  - Age and gender effects on postural stability and static balance in Thai community
      dwelling adults.
AB  - BACKGROUND: A study of postural stability was undertaken to identify the effects
      of age and gender as a preliminary study in one Thai community dwelling adults.
      It will be useful to prevent falls in the future. METHOD: The authors measured
      the postural stability in 120 males and females aged 30-40, 60-70 years using a
      Balance Master 8.0, Neurocom, OR to perform the modified Clinical Test for the
      Sensory Integration of Balance (mCTSIB) and the Unilateral Test protocols.
      RESULTS: The authors found that the females aged 60-70 were more stable than the
      males at the same age. CONCLUSION: Age and gender were significant variables that
      influence postural stability and static balance.

PMID- 16083174
TI  - The distribution of IL-10 promoter polymorphism in Thais.
AB  - IL-10 is a regulatory cytokine, which plays important roles in the pathogenesis
      of many diseases polymorphism of IL-10 promoter influences the phenotypic
      expressions such as the variation of IL-10 production among individuals and is
      subjected to the genetic susceptibility study of many diseases. However, there is
      no information about the frequencies of IL-10 promoter polymorphism in a Thai
      population. To determine the distribution of IL-10 promoter polymorphism in
      unrelated healthy Thais, genomic-DNA from 160 unrelated healthy volunteers were
      analyzed by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) method. The functional single-nucleotide polymorphisms (SNPs) in IL-10
      promoter (positions -1082 (G/A), -819 (C/T), -592 (C/A) were included. The allele
      frequencies of -1082*A (93.4%), -819*T (71.9%), and -592*A (71.9%) were
      significantly higher than the allele frequencies of -1082*G (6.6%), -819*C
      (28.1%), and -592*C (28.1%) respectively in a Thai population similar to other
      Asian populations (Korean, Japanese, Chinese). As for the haplotype analysis, the
      ATA haplotype (72%) was significantly higher in Thais and other Asian populations
      compared to non-Asian populations; whereas, GCC haplotype (6.6%) was
      significantly lower in Thais. Additionally, two rare haplotypes of IL-10 promoter
      (ATC and ACA) which were previously reported only in the Chinese Han people, were
      found with similar frequencies (0.6%) in the present study. In conclusion, the
      distribution of IL-10 promoter polymorphisms in Thais was comparable to other
      Asian populations but distinct from Non-Asian populations. At least five
      haplotypes existed in an unrelated healthy Thai population as ACC, GCC, ATA, ATC,
      and ACA haplotypes.

PMID- 16083175
TI  - No association between an interleukin 4 gene promoter (-589) polymorphism and
      Graves' disease in Thai patients.
AB  - Cytokines play a key role in the regulation of immune and inflammatory responses
      and therefore are potential candidate genes for autoimmune thyroid disease.
      Polymorphisms in cytokine genes may effect gene transcription, causing individual
      variations in cytokine production. Several investigators have linked the
      interleukin-4 (IL-4) gene and autoimmune disease. The present population-based
      study was to investigate the polymorphisms of IL-4 gene promoter (-589C/T) in GD
      patients compared with a control group and determine the association with GD in a
      Thai population. The subjects included 137 GD patients and 137 healthy control
      subjects with similar ethnic and geographic backgrounds. The IL-4 gene
      polymorphism at position -589 in the promoter was analyzed using the PCR-RFLP.
      The protective effect of the -589T allele as suggested by Hunt et al in a
      Caucasian population was not observed in the present study. The -589T allele
      frequencies were similar between patients and control subjects (69% vs 69.3%)
      suggesting that this polymorphism can not be used as a genetic marker for GD
      susceptibility in Thais.

PMID- 16083176
TI  - Prevalence of dengue virus in Aedes mosquitoes during dry season by semi-nested
      reverse transcriptase-polymerase chain reaction (semi-nested RT-PCR).
AB  - Dengue hemorrhagic fever remains a major health concern in Thailand. Much effort
      has focused on the prevention and control of the disease. Detection of dengue
      virus infection rate in mosquitoes would evaluate dengue control programs and
      predict the epidemics of dengue hemorrhagic fever. To determine dengue virus
      infection rate in mosquitoes by Semi-nested RT-PCR. A total of 400 mosquitoes
      were collected from Rom Kao Community representing a crowded community and
      another 9 non-crowded communities in Bangkok. Mosquitoes were then divided into
      40 pools, each contained 10 mosquitoes. A total of 391 Aedes aegypti and 9 Aedes
      albopictus were screened for dengue virus. The mosquito infection rate in the Rom
      Klao community was 5% of the mosquito pool equal to that found in non-crowded
      communities. Both groups were found to have dengue virus serotype 3. The present
      study suggests a circulation of dengue virus serotype 3 in both crowded and non
      crowed communities, the infection rates of which are indifferent during the dry
      season.

PMID- 16083177
TI  - Detection of pathogenic leptospiral DNA in urine by polymerase chain reaction.
AB  - Diagnosis of leptospirosis is currently based on serological tests detecting
      antibodies against the spirochete. The standard method is the microscopic
      agglutination test (MAT), which is serovar-specific, requires a period of
      antibody development, and increases the risk of exposure to viable organisms.
      Therefore, the present study aimed to develop a rapid, sensitive, specific, and
      safe method based on the PCR technique to detect pathogenic Leptospira in urine
      samples. Nested PCR using two sets of primers, external and internal primers,
      were shown to specifically amplify 16S rRNA target of patho-genic Leptospira. No
      amplification was observed when DNA from non-pathogenic Leptospira and other non
      Leptospira bacteria were used as DNA templates. The method was able to detect as
      few as 10 leptospires in urine. Therefore, nested PCR approach may be a useful
      tool for prompt and definitive diagnosis of leptospirosis.

PMID- 16083178
TI  - Induction of apoptosis by herpes simplex virus in Jurkat cells is partly through
      caspase-3, -8 and -9 activation.
AB  - Herpes simplex virus (HSV), a large DNA containing virus, is endemic in all human
      populations investigated. After infection of mucocutaneuos surfaces, HSV
      establishes a latent infection in nerve cells. Various immune evasion mechanisms
      have been shown to be utilized by HSV including apoptosis induction in
      Tlymphocytes. However, the mechanisms of T cell infection and apoptosis by HSV
      are still unknown. The present study investigated the molecular mechanisms of
      apoptosis induction in T cells by HSV The Jurkat T cell line was used as a
      representative for T cells. Apoptosis detection by Annexin Vassay demonstrated
      that both HSV-1 and HSV-2 induced apoptosis in Jurkat cells and caspase-3, -8,
      and -9 inhibitors blocked apoptosis induced by HSV-1 and HSV-2. The data
      suggested that HSV-1 and HSV-2 induced apoptosis in T lymphocytes by caspase
      dependent pathway. However, apoptosis may occur through other mechanism(s) since
      caspase inhibitors used in the present study could not completely inhibit
      apoptosis induced by HSV infection. In addition, the data demonstrated that the
      number of apoptotic cells induced by HSV-2 was significantly higher than byHSV-1
      at 12 hour post-infection (h p.i.) (p = 0.003). Further studies in peripheral
      blood T cells and the proteins of viruses involved in apoptosis induction should
      be further performed in order to elucidate the molecular mechanisms of apoptosis
      induced by these viruses.

PMID- 16083179
TI  - Establishment of cytotoxic T lymphocytes specific for autologous Epstein-Barr
      virus in HIV-infected patients: the feasibility study of EBV-specific
      immunotherapy for patients with EBV-associated lymphoma.
AB  - Cytotoxic T lymphocytes specific for Epstein-Barr virus (EBV) have previously
      been successfully used in immunotherapy of Posttransplant lymphoproliferative
      disease (PTLD) and Hodgkin's disease. A similar strategy has never been employed
      in HIV/AIDS patients who also have high risk of developing EBV-associated
      lymphoma. A total of 5 HIV-infected patients were enrolled to evaluate their EBV
      specific T cell responses by Interferon-gamma (IFNgamma) ELISpot assays. Most
      patients had detectable T cell responses, mainly directed at Epstein-Barr nuclear
      antigen (EBNA-3). The authors wanted to see whether it was possible to augment
      magnitude and spectrum of the EBV responses by stimulating patient PBMC with
      cells presenting autologous EBV antigens. The authors successfully established
      spontaneously EBV-transformed lymphoblastoid cell lines (EBVh-BCL) and used them
      for generation of EBV-specific CTL (EBV-CTL). The EBVh-CTL lines established in
      the present study were not only highly cytotoxic against the autologous virus but
      also able to secrete IFNgamma detected by ELISpot. The authors are now in the
      process of generating these lines in a large number and in a clinical grade for
      adoptive immunotherapy.

PMID- 16083180
TI  - MR imaging of CNS leiomyosarcoma in AIDS patients.
AB  - Leiomyosarcomas of the central nervous system are extremely rare; however they
      are becoming more prevalent in immunocompromised patients. The authors present
      MRI (Magnetic Resonance Imaging) of six cases of pathological proved
      leiomyosarcomas of the central nervous system in patients infected with human
      immunodeficiency virus. MR images of 4 cases of intraspinal leiomyosarcoma showed
      lobulated masses expanding multilevel of neural foramina with extradural and
      intradural extension, giving dumbbell appearance which mimic neurofibroma. Two
      cases of intracranial leiomyosarcoma revealed a mass at the left cavernous sinus
      involving prepontine cistern in one case and two lesions in the other case
      showing masses with dural based appearance at the region of the planum
      sphenoidale and the posterior aspect of the falx cerebri which mimiced a
      meningioma. The leiomyosarcoma should be included in the differential diagnosis
      of extra-axial CNS lesions in HIV-infected patients.

PMID- 16083181
TI  - Sonographic evaluation of the intrascrotal disease.
AB  - PURPOSE: To determine the causes of intrascrotal disease in patients who were
      sent for scrotal sonography at King Chulalongkorn Memorial Hospital and whether
      the imaging findings can help differentiate the tumor from infection of the
      testis. MATERIAL AND METHOD: Retrospective review was performed in 72 cases of
      extratesticular lesions and 48 cases of the intratesticular lesions to find out
      the causes of intrascrotal disease. The sonographic findings in the cases with
      final diagnosis of intratesticular infection and testicular tumor were analyzed
      according to the following criteria including the size of the testis, number,
      echogenicity, and margin of the mass, diffuse abnormal echogenicity of the
      testis, presence of fluid in the scrotal sac, epididymal lesion, scrotal skin
      thickening and calcification. RESULTS: Hydrocele was the most common
      extratesticular lesion (29.87%) and epididymitis was the second most common
      (14.28%). Infection was the most common intratesticular pathology (54.17%) and
      tumor was the second most common (31.25%). Most testicular tumors appeared as a
      focal mass while testicular infection usually caused diffuse abnormal
      echogenicity throughout the testis (p = 0.008). Epididymal lesions and skin
      thickening were usually detected together with intratesticular infection while
      they were not present in the cases of tumor (p = 0.000061 and 0.017). The number,
      echogenicity, margin of the mass, presence of testicular enlargement, fluid in
      the scrotal sac and calcification did not differ between testicular infection and
      tumor CONCLUSION: Hydrocele was the most common cause of extratesticular disease,
      followed by epididymitis. Most of the extratesticular pathology was benign
      entities. For intratesticular disease, the most common cause was infection,
      followed by intratesticular tumor Findings of a solitary intratesticular mass
      without epididymal lesion or skin thickening prefered malignant entity, while
      diffuse abnormal echogenicity of the testis with epididymal lesion and skin
      thickening prefered infectious process.

PMID- 16083182
TI  - Pattern of local-regional recurrence in patient with early breast cancer after
      mastectomy: an analysis of 357 cases at King Chulalongkorn Memorial Hospital.
AB  - A retrospective review was performed on 357 patients with early stage I-IIIA
      operable breast cancer who were treated with mastectomy and referred to the
      clinic at the Division of Radiation Therapy, Department of Radiology, King
      Chulalongkorn Memorial Hospital between Jan 1991 and Dec 2001. Patients
      characteristics, treatment modalities and pattern of local and regional failure
      were evaluated. The median and mean age in the present study were 49 and 50.2
      years, respectively. Stage I, II and IIIA were 10.9%, 79.6% and 9.5%,
      respectively. One hundred and ninety-seven patients (55.2%) received
      postoperative radiation therapy (RT). Adjuvant chemotherapy was given in 247
      patients (69.2%) while 122 patients (34.2%) received adjuvant hormonal therapy.
      Sixty one patients (17.1%) received both adjuvant chemotherapy and hormonal
      therapy. However, 12.6% (45/357) did not receive any adjuvant treatment. Median
      follow up time was 42.6 months (range 6-136 months). Ipsilateral supraclavicular
      node and chest wall were the most common sites of local-regional recurrence. The
      chest wall recurrence rate was 10.4% (37/357), which was 16.9% (27/160) in the
      non postoperative radiation (No RT) group and 5.1% (10/197) in the postoperative
      radiation (RT) group. For ispilateral supraclavicular node, the recurrence rate
      was 10.6% (38/357), which was 15.6% (25/160) and 6.6% (13/197) for non RT and RT
      groups, respectively. The incidence of ipsilateral axilla, ipsilateral internal
      mammary node and ipsilateral infraclavicular node recurrence rate were 4.2%, 3.6%
      and 0.8%, respectively. Overall, chest wall and ipsilateral supraclavicular node
      were the most common sites of local-regional recurrence in early stage operable
      breast cancer who underwent mastectomy Postoperative adjuvant radiation therapy
      decreased the risk of local-regional recurrence.

PMID- 16083183
TI  - Child abuse: radiographic findings at King Chulalongkorn Memorial Hospital.
AB  - OBJECTIVE: To describe radiographic findings in physically abused children.
      MATERIAL AND METHOD: The physically abused children diagnosed in King
      Chulalongkorn Memorial Hospital from 1998 to 2002 were retrospectively reviewed
      of medical records and radiographic imaging. RESULT: Eighteen of 30 physically
      abused children had positive radiographic findings and 15 of 18 were related to
      head injury. Subdural hematomas and skull fractures were the two most common
      findings found in 11 cases and 9 cases respectively. Seven of 11 cases of head
      injury had retinal hemorrhage. Fractures other than the skull were detected in 6
      patients, located at the long bones, ribs and spines. The abused children with
      positive radiographic findings were more commonly found in younger infants and
      mucocutaneous lesions might be absent. CONCLUSION: Inflicted head injury was the
      most common radiographic findings in the present series. Shaking-impact mechanism
      was likely to play a significant role in this group of patients.

PMID- 16083184
TI  - Abnormal findings in breast imaging: a hospital-based survey in 4264 Thai women.
AB  - OBJECTIVE: To evaluate the distributions of common and significant imaging
      findings from breast imagings at King Chulalongkorn Memorial Hospitals. MATERIAL
      AND METHOD: Data was collected from every mammography performed from November 1,
      2001 to October 31, 2002. The reports were analyzed and imaging findings were
      recorded. The ACR BI-RADS category was applied to all cases. RESULTS: There were
      4264 patients and all of them were female. The age range was between 19-90 years
      and average age was 50.1 years. The most common positive findings were cysts
      (39.22%), followed by focal lesions (14.76%), mass (8.69%), architectural
      distortion (7.83%), calcification (7.36%) and thick ducts (3.76%). According to
      ACR BI-RADS, most of the studies were in category 2 (42.59%), followed by
      category 1 (38.67%), category 3 (12.08%) category 5 (3.45%), category 4 (3.12%)
      and category 0 (0.09%). CONCLUSION: Breast imaging is the standard screening tool
      for breast cancer and can reveal different kinds of findings. Knowing the
      distribution of these findings helps both the radiologists to understand the
      scope of their work and the institution to audit their practice.

PMID- 16083185
TI  - Effectiveness of lubrication of endotracheal tube cuff with chamomile-extract for
      prevention of postoperative sore throat and hoarseness.
AB  - PURPOSE OF THE STUDY: To determine the efficacy of lubrication of the
      endotracheal tube cuff with Chamomile extract (Kamillosan M) before intubation on
      postoperative sore throat and hoarseness. MATERIAL AND METHOD: The authors
      randomly assigned 161 patients ASA (American Society of Anesthesiologists)
      physical status I, II elective surgical, orthopedic, gynecological or urological
      into 2 groups. The study group received 10 puffs of total 370 mg of Chamomile
      extract (Kamillosan M spray) lubricated at cuff of endotracheal tube while the
      control group did not receive any lubrication before intubation. Standard general
      anesthesia with tracheal intubation was given in both groups. Sore throat and
      hoarseness were recorded in post anesthetic care unit and at 24 h after
      operation. RESULTS: One hundred and sixty-one ASA physical status I, II elective
      surgical patients were recruited. Forty one out of 81 patients (50.6%) in the
      Chamomile group, scored no postoperative sore throat in the post-anesthesia care
      unit compared with 45 out of 80 patients (56.3%) in the control group p=0.386.
      Postoperative sore throat and hoarseness both in the postanesthesia care unit and
      at 24 h postoperation were not statistically different. There was no
      statistically significant relationship between sore throat or hoarseness and
      postoperative nausea or vomiting, ASA physical status, gender, history of
      smoking, grade of laryngoscopic view, number of intubation attempts, condition
      during intubation, use of oral airway and couching during extubation. CONCLUSION:
      Lubrication of endotracheal tube cuff with Chamomile extract spray before
      intubation can not prevent post operative sore throat and hoarseness.

PMID- 16083186
TI  - Clinical experiences of one--lung ventilation in adults using the Univent.
AB  - OBJECTIVE: To assess the clinical use and intraoperative problems of the Univent
      tube for one-lung ventilation (OLV). STUDY DESIGN: A cross-sectional descriptive
      study. MATERIAL AND METHOD: The records of 44 patients undergoing OLV with the
      Univent tube (Fuji System Corporation, Tokyo) at Chulalongkorn Memorial Hospital,
      Bangkok, Thailand from 1997 to 2003 were reviewed. The present study data
      included the techniques of the Univent blocker placement, frequencies of
      successful OLV being used as an alternative device after failed left-sided double
      lumen tube (LDLT), and related intraoperative problems during OLV. RESULTS: The
      blinded rotation method was used for 32 out of 44 cases of the Univent blocker
      placement, and the success rate of the correct sided placement on the needed
      bronchus was higher on the right (91.3%) than on the left (66.7%). Therefore,
      fiberoptic aided technique should be more appropriate for the left-sided
      blockade. Three successful intubations by the Univent after failed LDLT were
      found. Two of these had narrow glottic apertures, whereas the other had a stiff
      neck. Two successful patients after failed bronchial blockades by LDLT according
      to the anatomical deviation of the carina were demonstrated. However, clinical
      problems during OLV with the Univent tube were:--air trapping, inadequate OLV,
      herniated bronchial cuff and crossed contamination. CONCLUSION: The Univent tube
      can be an alternative to LDLT for OLV under the presence of available fiberoptic
      bronchoscopes, close monitoring and special precautions.

PMID- 16083187
TI  - Rapid ambulation and range of motion after minimally invasive total knee
      arthroplasty.
AB  - The authors evaluated the intraoperative data and early clinical results of 22
      minimally invasive mini-incision total knee arthroplasties (mini-incision TKAs)
      performed between October 2002 and September 2003. Results were matched with 22
      patients who underwent standard TKA in the same period. At a minimum 12-week
      follow up, results comparing the mini-incision TKA group and the standard TKA
      group were evaluated as follows: The average operative time was 137.1 vs 115.8min
      (p=0.02), the average wound length was 9.4 vs 13.7 cm, the average blood loss was
      456 vs 512 ml (p=0.14) and the number of patients who could start to walk on
      postoperative day one was 17 vs 2. On postoperative day one, 82% of the mini
      incision TKA group could do active knee extension meanwhile none of the standard
      group could. Postoperative pain score was not different at 24 hours or 48 hours.
      At 2 and6 weeks, the mini-incision TKA group had less pain with significant
      difference (p=0.002 and p=0.002). The postoperative range of motion in the mini
      incision group was also significantly improved at 2 weeks (p=0.03). However, pain
      and range of motion were not different in both groups after 12 weeks. Early
      results of mini-incision TKA accelerated patient postoperative activity,
      ambulation and range of motion.

PMID- 16083188
TI  - The influence of indoor environment quality on psychosocial work climate among
      office workers.
AB  - BACKGROUND: There is increasing concern about psychosocial problem in workplaces
      and indoor environmental quality (IEQ) is alleged to be among the major causes of
      this problem. PURPOSE: To investigate the influence of indoor environmental
      problems on psychosocial effect among office workers in Bangkok, Thailand. STUDY
      DESIGN: Cross-sectional descriptive study. METHOD: Study subjects were 1,262
      office workers selected by cluster random sampling from 5 air-conditioned
      buildings in Bangkok. The data were collected by self-administered questionnaires
      during February 2004. RESULTS: Office workers in an unhealthy climate group were
      significantly younger, had longer weekly working hours and higher educational
      levels. The prevalence rates of all categories of IEQ complaints were higher in
      the unhealthy climate group. In crude analyses, the odds ratios of having an
      unhealthy psychosocial work climate were significantly associated with the number
      of IEQ complaints in a dose-response manner After adjusting for a set of
      confounding factors (sex, age groups, education, job category and working hours),
      temperature, noise and dust are the aspects of IEQ complaints significantly
      associated with having an unhealthy psychosocial work climate. CONCLUSION: Good
      workplace IEQ would have beneficial effects on psychological well-being of
      employees.

PMID- 16083189
TI  - Nerve conduction studies in chronic arsenic poisoning patients.
AB  - OBJECTIVE: To assess the nerve conduction functions among female patients with
      arsenical dermatoses compared with the controls. DESIGN: Cross-sectional analytic
      study SUBJECTS AND METHOD: Thirty females with skin lesions consistent with
      arsenical dermatoses and 27 controls who met the inclusion criteria were
      investigated by nerve conduction functions. Case findings resulted from a house
      to-house survey in village 12, Ronphibun subdistrict and village 5, Saothong
      subdistrict, Nakhon Si Thammarat Province, southern Thailand in 1995. RESULTS:
      Differences between the arsenic-exposed population and the reference group
      regarding nerve conduction velocities (NCVs), proximal and distal latencies and
      amplitudes of sensory and motor nerve action potentials were not found except for
      the absent response to the sural nerve stimulation in three subjects of the
      exposed group. CONCLUSION: The effects of arsenic toxicity on the peripheral
      nerves in the form of slow nerve conduction velocities were not found among
      female patients with arsenical dermatoses in Ronphibun. Some patients might have
      experienced arsenic neuropathy to some degree in the past (before 1987) but they
      had recovered to some degree at the time of the present investigation (1996) as
      most of the patients with chronic arsenic poisoning in the present study changed
      their sources of drinking water from arsenic-contaminated shallow-well water to
      other sources such as rainwater, tap water or commercial bottled water.

PMID- 16083190
TI  - Cost of primary health care in universal insurance at Health Center 16, Bangkok
      Metropolitan Administration.
AB  - The purpose of the present study was to illustrate the cost of services in health
      promotion and prevention, out patient (OPD) and dental care in Health Center (No.
      16) Bangkok Metropolitan Administration. The analysis of the cost components
      could be used as key data for future planning, budgeting and resources preparing
      for the short and long terms. The cost centers were categorized to be executive,
      services and supporting unit. The simultaneous equation method was employed to
      allocate all costs from other associated cost centers to the service unit. The
      unit cost per visit was 372.76 baht, while the unit cost per capitation was
      532.83 baht. The unit cost of health promotion and prevention per capitation was
      288.95 baht, whereas the unit cost of OPD care per capitation was 183.47 baht and
      the unit cost of dental care per capitation was 55.37 baht. The labor cost
      accountedfor 83.67 per cent, capital cost 6.09 per cent and material cost 10.24
      per cent of the total cost. Unit costs of OPD and dental care were lower than the
      proposed budget while the unit cost of health promotion and prevention was
      higher. This could be due to some patients seeking OPD care from King
      Chulalongkorn Hospital instead, while the health promotion and prevention
      offering was more than that normally offered in other Health Centers. The
      improvement of labor efficiency and the decrease of labor cost would be the short
      and long run strategies respectively.

PMID- 16083191
TI  - Hyperbaric oxygenation and blood lactate clearance: study in sixty male naval
      cadets.
AB  - The research was aimed to study the effects of a 30 minute exposure to 2.5 ATA
      with 100% O2-inhalation on lactate concentration after muscular fatigue from
      incremental exercise on a cycle ergometer The subjects were 60 male naval cadets
      aged 20-23 years whose physical fitness was equivalent to the average athletes.
      All volunteers participated in the first VO2 max exercise test to obtain their
      baseline data and randomly assigned into 3 groups of 20. The 3 groups were: Rest
      recovery group (RR), Oxygen recovery group (OR), and the Hyperbaric oxygenation
      (HBO2) recovery group (HR). The volunteers took the incremental exercise test
      (Ordinary Lamp Protocol) on a cycle ergometer to exhaustion, then rested
      according to the above assigned groups. Blood samples were taken from each
      volunteer before the experiment, at exhaustion and every 5-minute intervals after
      the exhaustion for 30 minutes and immediately assayed for lactate concentration.
      The results showed significant decrease of blood lactate concentration at 15, 20
      and 25 minutes intervals after the exhaustion in the HR group compared to the
      others. It might be initially concluded that HBO2 enhanced the rate of lactate
      removal from peripheral blood vessels, therefore it shortened the recovery time.

PMID- 16083192
TI  - Clinical and virological differences between hepatitis B virus genotypes B and C:
      a case-control study.
AB  - OBJECTIVE: The pathogenic significance of hepatitis B virus (HBV) genotypes is
      undefined. The aim of this study was to elucidate the differences in clinical and
      virologicalfeatures between HBV genotypes B and C by conducting a case-control
      study in Thai patients who were chronically infected with the virus. PATIENTS AND
      METHOD: HBV genotyping was assessed by polymerase chain reaction (PCR) and
      restriction fragment length polymorphism (RFLP) method in stored sera of 470
      patients with chronic hepatitis B. Among these, 65 patients with HBV genotype B
      were enrolled and matched individually to those with HBV genotype C according to
      sex, age, and distribution of liver disease which included asymptomatic carrier,
      chronic hepatitis, cirrhosis and hepatocellular carcinoma. RESULTS: Serum alanine
      aminotransferase (ALT) was significantly higher in patients with genotype C than
      those with genotype B. Hepatitis B e antigen (HBeAg) was significantly more
      frequent in genotype C than genotype B patients (50.8 and 30.8%, respectively,
      p=0.03), but the levels of HBV DNA were comparable between them. Among patients
      who were positive for HBeAg, the mean age of genotype C patients tended to be
      older than genotype B patients. CONCLUSION: The present study demonstrated that
      patients with HBV genotype C had a significantly higher rate of HBeAg,
      experienced delayed HBeAg seroconversion and exhibited more severe liver disease
      compared to those with genotype B.

PMID- 16083193
TI  - Low dose creatine supplementation enhances sprint phase of 400 meters swimming
      performance.
AB  - This study demonstrated the effect of low dose creatine supplement (10 g. per
      day) on the sprinting time in the last 50 meters of 400 meters swimming
      competition, as well as the effect on exertion. Nineteen swimmers in the
      experimental group received creatine monohydrate 5 g with orange solution 15 g,
      twice per day for 7 days and nineteen swimmers in the control group received the
      same quantity of orange solution. The results showed that the swimmers who
      received creatine supplement lessened the sprinting time in the last 50 meters of
      400 meters swimming competition than the control group. (p<0.05). The results of
      Wingate test (anaerobic power, anaerobic capacity and fatigue index) compared
      between pre and post supplementation. There was significant difference at p<0.05
      in the control group from training effect whereas there was significant
      difference at p<0.000 from training effect and creatine supplement in the
      experiment group. Therefore, the creatine supplement in amateur swimmers in the
      present study enhanced the physical performance up to the maximum capacity.

PMID- 16083194
TI  - Detection of polycyclic aromatic hydrocarbon exposure from automobile exhaust
      fumes using urinary 1-hydroxypyrene level as an index.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are hydrocarbon compounds which originate
      from incomplete combustion. In humans, PAHs are bioactivated to reactive
      metabolites which can bind covalently to DNA and subsequently initiate mutation
      and carcinogenesis. The measurement of PAHs exposure may be used as an index to
      classify a cancer risk group. The purpose of the present study was to measure the
      level of urinary 1-hydroxypyrene, a metabolite of PAHs, in subjects exposed to
      automobile exhaust fumes compared to non-exposed subjects. A urine sample was
      collected from each individual subject after the end of a working day and
      quantitated for 1-hydroxypyrene and creatinine by HPLC and spectrophotometric
      method, respectively. The results showed that average urinary 1-hydroxypyrene
      level in exposed subjects was significantly higher than non-exposed subjects
      (mean +/- SD of 0.0035 +/- 0.0032 and 0.0011 +/- 0.0010 micromol/l, respectively;
      P = 0.000). Average urinary creatinine level in exposed subjects was also
      significantly higher than non-exposed subjects (mean +/- SD of 0.01 +/- 0.005 and
      0.008 +/- 0.006 mol/l, respectively; P = 0.040). The ratio of urinary 1
      hydroxypyrene/mol creatinine level, of the exposed subjects was significantly
      higher than that of the non-exposed subjects (mean +/- SD of 0.37 +/- 0.28 and
      0.19 +/- 0.22 micromol/mol creatinine, respectively; P = 0.002). CONCLUSION:
      Automobile exhaust fume exposed subjects have a higher risk to be exposed to PAHs
      than the non-exposed subjects. Urinary 1-hydroxypyrene level can be used as an
      index for an exposure of PAHs which have originated from automobile exhaust fumes
      and other sources as well.

PMID- 16083195
TI  - Bioequivalence study of postcoital emergency contraceptions containing
      levonorgestrel.
AB  - OBJECTIVE: The progestogen-only method of emergency contraception,
      levonorgestrel, is one of the effectiveness in preventing expected pregnancies.
      The comparative bioavailability was carried out on levonorgestrel tablets (0.75
      mg) from two different sources (Hungarian and Thai made). METHOD: Eighteen
      healthy female volunteers were given a single oral dose of 0.75 mg tablets in a
      crossover design. Serum levonorgestrel concentration was determined by radio
      immunoassay. The pharmacokinetic analysis of serum levonorgestrel concentration
      from each treatment was established. The comparative bioavailability of the two
      products was determined by the analysis of variance (ANOVA) for two way crossover
      design. RESULTS: The results found that the mean peak (X +/- SD) serum
      concentration (Cmax) of the Thai-made pill and Hungarian-pill were 1.18 +/- 0.12
      and 1.14 +/- 0.10 ng/ml, respectively. The 90% confidence intervalfor the
      difference of log Cmax mean was 99.54-120.78%. The time to peak serum
      concentration (Tmax) of the Thai-made pill and Hungarian-pill were 1.56 +/- 0.73
      and 1.58 +/- 0.67 hrs, respectively. The different time of peak serum
      levonorgestrel concentration was 1.27%. The mean area under the curve (AUC) of
      Thai-made pill and Hungarian-pill were 2.14 +/- 0.21 and 2.09 +/- 0.16 ng.h/ml,
      respectively. The 90% confidence interval for the difference of log AUC mean was
      103.27 - 121.89%. CONCLUSION: The present study revealed that the 90% confidence
      interval for the difference of log Cmax mean and log AUC mean were in the
      criteria of acceptance, which should be within 80-125%. So, the authors can
      conclude that the Thai-made pill was bioequivalent to the Hungarian-pill.

PMID- 16083196
TI  - Intra-operative diagnosis in surgical neuropathology: a study of 120 cases with
      reference to squash cytology.
AB  - OBJECTIVE: To present results of intra-operative consultation in surgical
      neuropathology and discuss the diagnostic guideline for squash cytology. MATERIAL
      AND METHOD: The intra-operative pathological diagnosis of 120 neurosurgical
      specimens was compared with the final histologic diagnosis. Squash preparation
      was used solely in 83 cases, frozen sections alone in 3 cases, and both
      techniques in the remaining. An algorithm for cytologic diagnosis was described.
      RESULTS: The intra-operative pathological diagnoses in neurosurgery were
      completely (83%) and partially (13%) correlated with the final results.
      CONCLUSIONS: Intra-operative diagnosis in surgical neuropathology is reliable.
      Squash cytology is highly recommended as an alternative approach.

PMID- 16083197
TI  - Extranodal malignant lymphoma of the upperaerodigestive tract in King
      Chulalongkorn Memorial Hospital according to WHO classification.
AB  - BACKGROUND: The Working Formulation commonly used to classify NHL in Thailand has
      been recognized as imperfect for primary extranodal lymphoma, especially in head
      and neck regions. OBJECTIVE: To study the clinicopathological and
      immunohistochemical features of extranodal malignant lymphoma of the upper
      aerodigestive tract according to WHO classification. SETTING: King Chulalongkorn
      Memorial Hospital. DESIGN: Descriptive study. PATIENTS: 77 Thai patients who
      presented between 1998 and 2003. METHODS: Routine histology was performed and
      stained with H&E and immunohistochemistry, and clinical characteristics were
      recorded. RESULTS: The patients included 42 males and 35 females, with an average
      age of 53.87 years. Tumor sites were as follows: Waldeyer ring (n = 42, 54.55%),
      sinonasal areas (n = 19, 24.67%), oral cavity (n = 9, 11.69%), hypopharynx (n =
      4, 5.19%), and larynx (n = 3, 3.90%). Immunohistochemically, 57 tumors (74.02%)
      were of B-cell phenotype and 19 tumors (24.68%) were of T-cell phenotype.
      According to the WHO classification, 45 cases (58.43%) were large B-cell, 3
      (3.90%) were Burkitt, 3 (3.90%) were marginal zone B-cell lymphomas of mucosa
      associated lymphoid tissue (MALT), 4 (5.19%) were follicular lymphoma, 1 (1.30%)
      was precursor B-lymphoblastic lymphoma, and 1 (1.30%) were mantle cell lymphoma.
      Among the T-cell lymphomas, 9 (11.69%) were of peripheral T-cell lymphoma,
      unspecified, 9 (11.69%) were extranodal NK/T cell lymphoma, nasal type, and 1
      (1.30%) were anaplastic large-cell lymphomas. In nasal cavity, 8 tumors (42.11%)
      were extranodal NK/T-cell lymphoma, nasal type, 5 (26.32%) were diffuse large B
      cell lymphoma, 4 (21.05%) were peripheral T-cell lymphoma, unclassified, and 1
      (5.26%) was Burkitt lymphoma. CONCLUSION: Our data correspond with series from
      Japan, Hong Kong, and Korea, but there is a significant difference from Western
      population in T-cell lymphomas of sinonasal area especially extranodal NK/T cell
      lymphoma of nasal type and peripheral T-cell lymphoma, unspecified which had a
      higher frequency in Thailand, Japan, Hong Kong, and Korea.

PMID- 16083198
TI  - Metastatic potentiality of micropapillary and conventional histological patterns:
      a comparative study of 82 pulmonary adenocarcinomas.
AB  - BACKGROUND: The recently described micropapillary pattern (MPP) is potentially a
      strong unfavorable prognostic marker for adenocarcinoma of the lung. None of the
      previous studies compared the association to nodal metastasis between
      conventional histological patterns and MPP. METHOD: Histological patterns
      (1=solid, 2=poorly formed acinar 3=well formed acinar, 4=papillary,
      5=bronchioloalveolar), and MPP were semiquantitatively evaluated in 82 pulmonary
      adenocarcinomas and correlated with nodal status. RESULTS: Mean percentages of
      pattern 1 and 2 are higher in node positive (N+) group (33.9% vs 19.3%, p=0.046;
      and 20.8% vs 13.4%, p=0.19, respectively). Analysis of the combined amount of
      pattern 1 and 2 revealed increased statistical significance (54.6% vs 32.5%,
      p=0.007). Mean percentages of pattern 3, 4 and 5 tended to be lower in N+ group
      (22.8% vs 29.4%, p=0.24; 2.8% vs 6.2%, p=0.33; and 17.9% vs 31.2%, p=0.053,
      respectively). Analysis of the combined amount of pattern 3, 4 and 5 showed
      increased statistical significance (43.3% vs 66.8%, p=0.005). Mean percentage of
      MPP was higher in N+ group (28.3% vs 11.3%, p=0.0007) after excluding the cases
      with more than 80% percent of pattern 1 and 2. The criterion of MPP > or = 20% or
      combined pattern 1 and 2 > 50% of tumor is strongly associated with nodal
      metastasis (p=0.0015). Pattern 1 has the highest rate of correspondence of having
      a similar pattern in metastases (18/26, 69.2%), followed by MPP (10/19, 52.6%),
      and pattern 2 (12/23, 52.2%). CONCLUSION: MPP has comparable metastatic impact to
      the solid and the poorly formed acinar patterns and it is prognostically
      informative to document the presence or absence of the solid plus poorly formed
      glandular pattern > 50% and MPP > or = 20% when histological subtype is
      evaluated.

PMID- 16083199
TI  - Weekly rescreening of 10% of the total cervical Papanicolaou smears: a worthwhile
      quality assurance scheme.
AB  - BACKGROUND: In awareness of possible false negative cervical Papanicolaou tests
      in routine service, the authors developed and tested a new scheme that would be a
      practical adjunct in quality assurance. OBJECTIVE: To evaluate the value of a
      weekly rescreen of 10% of the total cervical Papanicolaou smears as a quality
      assurance scheme. DESIGN: A prospective descriptive study. RESULTS: Of 31,914
      slides in the 9-month study period, a total of 3,097 slides (9.7%) were picked up
      in the rescreen scheme. There were 29 discordant cases (0.9%) consisting of 7
      cases (0.2%) of errors from the initial reporting, 2 cases of errors from the
      rescreening and 20 other cases from disagreements on designating atypical
      squamous cells of undetermined significance. The errors of the initial reports
      could be further classified into 6 cases due to screening errors and one case
      because of interpretation error. The proper diagnoses had been revised and resent
      to the attending gynecologists. CONCLUSION: A weekly rescreening 10% of total
      cervical Papanicolaou smears scheme was worthwhile for quality assurance. It
      could be used for evaluating screener performance and create internal quality
      improvement. The detected false diagnoses were manageable.

PMID- 16083200
TI  - Social support in depressed patients who attempted suicide.
AB  - OBJECTIVES: To identify the level of perceived social support in depressed
      patients who attempted suicide and to determine whether perceived social support
      is associated with suicidal attempt in depressed patients. MATERIAL AND METHOD:
      The sample consisted of 90 patients who presented with suicidal attempt and had
      clinical depression and 90 depressed patients who had never attempted suicide.
      The subjects were clinically assessed for depression, availability of social
      support and their satisfaction, number of friends and consultants and family
      history. Subjects were recruited at King Chulalongkorn Memorial Hospital from
      July 2000 to June 2002. RESULTS: The depressed patients who attempted suicide had
      lower mean scores in all areas of perceived social support and reported having
      fewer friends and consultants than those without suicidal attempt. They also had
      a higher rate of financial problems, substance abuse and family history of
      alcohol or substance use disorder. The scores for severity of depression and
      level of perceived social support were negatively correlated with statistical
      significance. CONCLUSION: Depressed patients who attempted suicide were more
      likely to report fewer of friends and a lower level of social support. Assessment
      of patient's support network as well as their perception of available social
      support should be included in the evaluation of depressed patients particularly
      in those with substance use disorder and intervention to prevent suicide should
      focus more on increasing their capacity to obtain social resources and modulating
      their perception.

PMID- 16083201
TI  - Effectiveness of lumbar traction with routine conservative treatment in acute
      herniated disc syndrome.
AB  - OBJECTIVE: To assess the effectiveness of lumbar traction with routine
      conservative treatment in acute herniated disc syndrome. DESIGN: Randomized
      double-blind controlled trial. SETTING: Outpatient clinic of physical medicine
      and rehabilitation. METHOD: 120 participants who met the diagnostic criteria of
      acute herniated disc syndrome were randomized into two groups. The study group
      received treated traction, and the control group received sham traction. All
      patients had routine conservative treatments (consisting of NSAIDs, instruction
      of proper back activity and precaution, back exercise, and heat modality). The
      main outcome measurement was the Oswestry score, which was collected on the first
      day and at the 4th week of the treatment. At the end of the study, all patients
      recorded global improvement and satisfaction. RESULTS: Of 120 patients divided
      into two groups equally, 12 and 6 cases in the control and intervention groups
      dropped out of the study. The mean (SD) change of the Oswestry score were 19.25
      (15.9) and 25.25 (16.68) in control and intervention groups respectively. There
      was no significant difference between the two groups with the p-value of 0.067
      and 95%CI of - 0.42-12.43. Approximately 89% of patients in each group had
      improvement of their symptoms, and 90% in each group were satisfied with lumbar
      traction. Co-intervention with heat modality, NSAIDs use and back exercise did
      not differ between the two groups. CONCLUSION: The data do not support the
      benefit of traction for patients with acute herniated disc syndrome. The patient
      can be conservatively treated at home with proper instruction.

PMID- 16083202
TI  - Prevalence of parasitism among students of the Karen hill-tribe in Mae Chame
      district, Chiang Mai province, Thailand.
AB  - Infection caused by intestinal parasites is still a common health problem in a
      poor-hygiene population especially for children in developing countries. A cross
      sectional study was conducted among 781 Karen students (age: 3 to 19, males: 325,
      females: 456) to determine the current status of intestinal parasitic infections
      in a mountainous area in the North of Thailand. The study was drawn from three
      schools in the Doi Inthanon region, in Mae Chame district of Chiang Mai province,
      from December 2002 to June 2003. The techniques used for the diagnosis were:
      stool concentration by using the 'formalin-ether' technique and perianal region
      examination by using the 'Scotch-tape' technique. The average rate of intestinal
      parasites for the group tested using the stool concentration technique was 42.06%
      (male: 46.87%, females: 38.82%); and 22.66% (males: 28.92%, females: 18.20%) when
      using the Scotch-tape technique.Among helminth-infected individuals, enterobiasis
      was found at the highest prevalence (15.49%). Other common infections were
      ascariasis (9.78%), trichuriasis (5.90%) and hookworm infection (2.20%).
      Strongyloildiasis was found only in 0.92%. For protozoa infection, the major
      cause is the non-pathogenic species "Entamoeba coli" (27.68%). The other non
      pathogenic protozoa (Endolimax nana, Chilomastix meslini and Iodamoeba butschlii)
      had a low prevalence from ranged 0.18%-4.79%. The prevalence of pathogenic
      Giardia lamblia infection was 2.21%. Entamoeba histolytica infection was found in
      only one case. Based on the two techniques used, the results from the Scotch-tape
      provided a higher sensitivity for the detection of Taenia spp. and Enterobius
      vermicularis eggs. Drug treatment was given to all the infected students. School
      based health education should be implemented in order to prevent and control the
      infections.

PMID- 16083203
TI  - The management of acardiac twins at King Chulalongkorn Memorial Hospital: case
      series.
AB  - Acardiac twin is a rare event with high perinatal mortality rate and the
      management strategies remain controversial. The authors report 4 cases of twin
      pregnancies associated with one acardiac twin diagnosed at King Chulalongkorn
      Memorial Hospital during the period 1993 to 2002. Two cases were expectantly
      managed and intrauterine interventions were performed in order to occlude
      umbilical artery of the acardiac twin in 2 cases, by using Guglielmi detachable
      coil (GDC) embolization and absolute alcohol injection. Overall, the perinatal
      mortality rate for the pump twin was 50% and the survival rate of expectant
      management in the present series was 100%. GDC embolization was judged to be
      technically successful since it completely occluded the circulation to the
      acardiac twin. However, the pump twin was dead which might have resulted from the
      compromised state due to cardiac failure. At present, it seems that conservative
      management with close antenatal surveillance is the treatment of choice when the
      twin-weight ratios are substantially less than 70%. Invasive techniques should be
      considered when there is ultrasound evidence of hydramnios or congestive heart
      failure of the pump twin at a previable gestational age.

PMID- 16083204
TI  - Adenovirus hemorrhagic cystitis in a stem cell transplant patient: the first
      reported case in Southeast Asia.
AB  - Adenovirus (AdV) infections are prevalent in bone marrow transplant patients,
      usually associated with significant morbidity and mortality. Hemorrhagic cystitis
      (HC) is a major complication mainly attributed to this virus. The authors report
      a case of AdV HC in a myelodysplastic patient undergoing peripheral blood stem
      cell transplantation. The diagnosis was confirmed by positive urine AdV antigen
      using indirect immunofluorescence assay. The patient gradually improved after
      adequate hydration, supportive treatment and reduced dose of cyclosporine, and
      was discharged on the ninth day of hospitalization. To the authors' knowledge,
      this is the first case of AdV HC in stem cell transplantation in Southeast Asia.

PMID- 16083205
TI  - Acute renal failure in a child with jellyfish contact dermatitis.
AB  - A 7-year-old boy suffered from jellyfish contact dermatitis and acute renal
      failure following a jellyfish sting. Three days before being admitted, he
      accidentally contacted a jellyfish on the left forearm, left thigh and trunk
      while wading at Pattaya beach, Eastern Thailand. Investigation revealed
      hemoglobinuria. Histologic findings of a renal biopsy indicated that acute
      tubular necrosis had caused acute renal failure in the present patient.
      Supportive treatments improved the dermatitis and renal function of this patient.

PMID- 16083206
TI  - Effect of Helicobacter pylori infection and NSAIDs on the risk of peptic ulcer
      bleeding.
AB  - Peptic ulcer bleeding remains an important emergency situation with a high
      incidence and carries significant morbidity and mortality. Current evidence
      suggests that H. pylori and NSAIDs increase the risk of peptic ulcer bleeding and
      these two factors seem to act independently. Testing for, and cure of, H. pylori
      infection is recommended in patients prior to the initiation of NSAID therapy and
      in those who are currently receiving NSAIDs and have a history of peptic ulcer
      bleeding. For patients who present with peptic ulcer bleeding but require NSAIDs
      long-term, H. pylori eradication therapy should be considered, followed by
      continuous proton pump inhibitor prophylaxis to prevent re-bleeding, regardless
      of which kind of NSAID (nonselective NSAID/coxib) is being prescribed. The
      success of eradication should always be confirmed because of the risk of peptic
      ulcer recurrences and bleeding complication.

PMID- 16083207
TI  - Magnetic resonace imaging study in major psychiatric disorders.
AB  - Magnetic resonance brain imaging provides good contrast between the three
      principal compartments of the brain: gray and white matter, and cerebrospinal
      fluid (CSF). Not only brain volumic and structural understanding, the application
      of magnetic imaging techniques as in Functional MRI (MRI), Magnetic resonance
      spectroscopy (MRS) also has greatly enhanced the range of findings in brain
      function of psychiatric patients. The objective of this paper was to present a
      brief review of the technological advances in magnetic neuroimaging, and to
      indicate how these techniques have impacted the study ofpsychiatry. Reviews of
      recent researches, examples of imaging techniques, and major findings for
      schizophrenia, affective disorder, anxiety, personality and other major
      psychiatric disorders are offered. In summary, the using of magnetic neuroimaging
      as an aid to diagnosis is discussed, and findings from the most accessible
      imaging techniques are reviewed.

PMID- 16083208
TI  - Pneumocystis pneumonia: an update.
AB  - Pneumocystis pneumonia is a major cause of illness and death in immunocompromised
      hosts. The numbers of pneumocystis pneumonia cases in Thailand have increased
      each year from 1992 to 2000 and peaked in 2000 at 6,255 cases. The microbe that
      causes pneumocystis pneumonia in humans is called Pneumocystis jirovecii.
      Pneumocystis sp. was discovered nearly a century ago, but the knowledge of
      Pneumocystis sp. remained poorly understood, until the molecular biology
      techniques help scientists verify it fungus nature. In the past, Pneumocystis sp.
      was misclassified as protozoan due to its morphologic features. Later, it was
      reclassified as fungus due to DNA analysis. Cotrimaxazole, the combination of
      trimethoprim-sulfamethoxazole, is the drug of choice for treatment and
      prophylaxis of pneumocystis pneumonia. However, increasing evidence of mutations
      in the enzyme dihydropteroate synthase (DHPS), the target of sulfa drugs
      represent emergence of sulfa resistance.

PMID- 16083209
TI  - Tubal abnormalities in Thai infertile females.
AB  - OBJECTIVE: To determine the prevalence of tubal abnormalities among infertile
      patients attending the clinic at Srinagarind Hospital. DESIGN: A descriptive
      study SETTING: Infertility clinic, Srinagarind Hospital, Faculty of Medicine,
      Khon Kaen University, Thailand. SUBJECT: A total of 740 female patients presented
      at the infertility clinic, Srinagarind Hospital between 1 January 1998 and 31
      December 2002. MATERIAL AND METHOD: A retrospective review of demographic data,
      baseline infertility information and the results of tubal assesments (including
      both hysterosalpingography and laparoscopy) were conducted. MAIN OUTCOME MEASURE:
      Prevalence of tubal abnormalities in infertile females being treated in the
      infertility clinic during the study period. RESULTS: Among the 740 patients being
      recruited to the present study, 533 cases (72.03%) were diagnosed with primary
      infertility while the rest (207 or 27.97%) came to the clinic due to secondary
      infertility. The mean infertile period of all study subjects was 4.68 years.
      Regarding the methods used for tubal assessments, hysterosalpingography (HSG),
      laparoscopy and combination of the two methods were conducted in 556 cases
      (75.14%), 30 cases (4.05%) and 154 cases (20.81%), respectively. The prevalence
      of tubal abnormalities demonstrated in the present study was 27.30% (202 from 740
      cases). Among the 202 patients with tubal abnormalities, the pathologies detected
      were cornual occlusion (46.04%), combined tubal abnormalities (30.20%), distal
      tubal occlusion (8.42%), hydrosalpinx (3.47%), peritubal adhesion (3.96%), and
      other abnormalities (7.91%). Other pelvic pathologies detected from laparoscopy
      were endometriosis (61.49%), pelvic adhesion (24.22%), leiomyoma (12.42%), and
      ovarian cyst (1.87%). CONCLUSION: Tubal abnormalities were detected in over one
      fourth of all infertile females being treated at Srinagarind Hospital. Further
      study investigating the etiologies of these abnormalities is needed since it
      could be the measure to bring down the occurrence of such conditions.

PMID- 16083210
TI  - Experience of the first 50 cases of cordocentesis after training with model.
AB  - OBJECTIVE: To describe the experience of the first 50 cases of cordocentesis
      after practicing with cordocentesis model. MATERIAL AND METHOD: Cordocentesis
      model consisted of a water-filled transparent glass box covered with a rubber
      latex sheet with or without piece of pork skin. A 30-cm umbilical cord filled
      with mercurochrome, hung inside the container, was the target for the puncture.
      As in real practice, the trainee had to try to aspirate the red mercurochrome
      from the umbilical cord using a spinal needle under ultrasonographic guidance.
      After practicing with the model for 300 procedures, the trainee was allowed to
      perform cordocentesis on pregnant women at gestational age of 18-22 weeks by
      herself under expert supervision with time limit of 30 minutes. The procedure not
      successful in 30 minutes was considered failure. Duration of procedures,
      placental site, puncture site, and related complications were recorded for
      subsequent analysis. RESULTS: After practicing with model for 300 procedures,
      real cordocentesis was performed by the trainee on 50 pregnant women. The success
      rate in obtaining fetal blood within 30 minutes was 100%. Most of them (92%) took
      less than 10 minutes to complete the procedure. Puncture site bleeding and fetal
      bradycardia were the most common immediate complications, found in 30% and 8%
      respectively, and spontaneously resolved within few minutes. CONCLUSION: Without
      any fetal and maternal jeopardy, cordocentesis model is simple, inexpensive but
      highly effective for the beginner to gain their experience, skill and prepare
      themselves for cordocentesis with confidence. However, the reduction of fetal
      loss rate with the training program remains to be further tested.

PMID- 16083211
TI  - Video-assisted thoracoscopic surgery (VATS) in the diagnosis and treatment of
      intrathoracic diseases at Ratchaburi Hospital.
AB  - OBJECTIVE: To review the authors' experience and benefit in diagnosis and
      management of intrathoracic diseases by Video-assisted thoracoscopic surgical
      procedures (VATS) using a non trocar technique. MATERIAL AND METHOD:
      Retrospective review of sixty-eight consecutive patients who underwent seventy
      one VATS procedures between January 1997 and December 2004. Indications included
      recurrent or persistent pneumothorax (n = 21 patients), empyema thoracis (17),
      lung nodules or masses (8), clot haemothorax (6), pleural effusion (4), pleural
      thickening or masses (3), mediastinal masses or cysts (3), pericardial effusion
      (2), removal of bullets from the pleural cavity (2), bronchiectasis with
      hemoptysis (1) and inspection of diaphragmatic injury (1) (Table. 1). An
      alternative method of manipulating thoracoscopic instruments without using a
      trocar was described. RESULTS: Of the 71 VATS procedures in 68 patients, 62
      (87.3%) procedures were successfully performed in 59 patients. Three of them
      underwent VATS bilaterally. (1 Tuberculous empyema and 2 spontaneous
      pneumothorax). Four patients requried conversion to thoracotomy due to bleeding
      in 1 who had excision lung bleb, extensive adhesion in 2 with chronic empyema
      thoracis and unlocated lesion in 1 with solitary pulmonary nodule (SPN). There
      were 5 postoperative complications: prolonged air leak for more than 7 days was
      seen in 4 patients. This complication occurred in a patient with spontaneous
      pneumothorax (3 patients) and bilateral tuberculous empyema at the left side (1
      patient). Wound infection and mild effusion occurred in 1 patient with unilateral
      tuberculous empyema (no additional drainage was required). VATS in diagnostic
      procedures were effective in 90% (9 of 10 patients) and the procedures were 4
      wedge excision, 3 pleural biopsies, 1 wedge excision for interstitial lung
      disease 1 inspection of diaphragmatic injury and 1 required conversion. Sixty one
      therapeutic procedures were effective in 50 patients (85.9%) (50 of 58 patients).
      None of them had a recurrence of pneumothorax after VATS procedures or other
      complications. Only small doses of analgesics were needed. There was no
      intraoperative mortality. The mean operative time was 67 minutes and the average
      postoperative hospital stay was 5.4 days for successful VATS group. CONCLUSION:
      VATS using of a non-trocar technique is a safe and effective method for diagnosis
      and treatment of intrathoracic diseases. Patients had benefit in reduced
      postoperative pain, short hospitalization, short recovery times and good cosmetic
      result.

PMID- 16083212
TI  - Fractional excretion magnesium (FE Mg) in systemic lupus erythematosus.
AB  - BACKGROUND: Tubulointerstitial fibrosis is an index of clinical severity. FE Mg
      has been delineated to correlate directly with the magnitude of
      tubulointerstitial fibrosis in clinical setting of glomerulonephropathy. A
      correlation between FE Mg tubulointerstitial fibrosis has never been assessed in
      nephritis associated with systemic lupus erythematosus. MATERIAL AND METHOD:
      Thirty-six patients diagnosed of having lupus nephritis were included for the
      determination of renal functions namely creatinine clearance, FE Mg, urinary
      protein. Of these 36 patients, 18 patients were associated with intact
      tubulointerstitial structure (group I) and 18 age matched patients were
      associated with tubulointerstitial fibrosis (group II) RESULTS: The mean FE Mg
      observed in group I was 1.5 +/- 0.3 which differed significantly from that
      observed in group II; 2.6 +/- 1; p = 0.006. CCr, total urinary protein, systolic
      and diastolic pressure were not significantly different between the two groups.
      CONCLUSION: FE Mg is a sensitive marker for the detection of tubulointerstitial
      disease in lupus nephritis. It is useful in early screening of disease severity
      in systemic lupus erythematosus.

PMID- 16083213
TI  - Retrospective study of patients with suspected inborn errors of metabolism at
      Siriraj Hospital, Bangkok, Thailand (1997-2001).
AB  - INTRODUCTION: This retrospective clinical study was carried out on patients with
      suspected inborn errors of metabolism (IEM) at Siriraj Hospital during 1997-2001.
      The authors investigated 114 patients by quantitative plasma amino acid analysis.
      OBJECTIVE: The objective of this study was to collect and analyze epidemiologic
      and specific clinical data of IEM, especially in small-molecule diseases.
      MATERIAL AND METHOD: All patients were categorized into 2 major groups. 1)
      positive diagnoses for IEM 2) negative diagnoses for IEM. The two groups were
      investigated, studied including statistical analysis. RESULTS: The authors found
      that most IEM ascertained through plasma amino acid analysis were small-molecule
      diseases (74.3%) and amino acid disorders consisted of the most frequent
      disorders. The presented data demonstrated that the ratio of positive diagnoses
      to all patients studied was 1:8. Epidemiological data showed there were more male
      than female patients. Onset of diseases occurred predominantly during the first
      month of age, and was rarely found after 3 years of age. There were histories of
      consanguinity in half of the IEM patients. The most common presenting symptom was
      acute metabolic encephalopathy and specific signs for small-molecule disorders
      included hepatomegaly, unusual urine odor, acidosis, hyperammonemia, alteration
      of consciousness, and ketosis/ketonuria. These signs or symptoms indicated
      further metabolic investigations. CONCLUSION: Comparison of the data from
      Thailand with other countries showed both similarities and differences to the
      Caucasian population. Thus, further studies in IEM are much needed for the Thai
      population.

PMID- 16083214
TI  - Respiratory complication of tsunami victims in Phuket and Phang-Nga.
AB  - In the present report the authors describe the clinical and laboratory findings
      of 26 tsunami victims admitted to the Phuket and the Takua Pa Hospital. Patients
      were classified into 4 groups of severity. class 1, baseline examination negative
      (n = 1); class 2, baseline examination positive but mechanical ventilation not
      needed on admission (n = 15); class 3, mechanical ventilation required on
      admission (n = 9); class 4, cardiopulmonary arrest (n = 1). On admission, 21/23
      patients had fever of > 37.5 C. 3/10 patients had hypernatremia and 7/10 cases
      had metabolic acidosis. The radiological manifestation varied from focal disease
      to diffuse infiltrations, either reticulonodular or patchy lesions. There were 3
      clinical courses among diffuse diseases: 1) diffuse infiltrations and progression
      3 cases 2) diffuse infiltration, early regression followed by progression 2 cases
      3) diffuse infiltration and steady regression 5 cases. Late complications
      comprised of pneumothorax/pneumomediastinum (n = 5) and bacterial pneumonia (n =
      18). The authors got culture data in 9 patients, most of them were infected with
      aerobic gram -ve bacteria and 2 of them were B. pseudomallei. The prognosis in
      the tsunami related medical illness was favorable. Only 2 patients (7.7%) died in
      the present study.

PMID- 16083215
TI  - Epilepsia partialis continua as a manifestation of hyperglycemia.
AB  - A review of 22 patients who presented with the syndrome of epilepsia partialis
      continua as symptoms of hyperglycemia and occurred during the phase of
      hyponatremia and mild hyperosmolality. Epilepsia partialis continua persisted for
      an average of 9 days,and its duration correlated with the degree of hyponatremia,
      low blood urea nitrogen(BUN) and measured serum osmolality. In all patients,
      epilepsia partialis continua was the first symptom leading to the diagnosis of
      diabetes mellitus. The epilepsia partialis continua ceased by normalization of
      blood glucose level. All patients survived and did not have any complications.
      The majority of the patients had evidence of a localized structural brain lesions
      and low serum sodium. Metabolic abnormalities including hyperglycemia,mild
      hyperosmolality and hyponatremia contribute to the development of
      epilepsiapartialis continua in an area of focal brain damage. It is important to
      determine blood glucose levels in all cases of epilepsia partialis continua.

PMID- 16083216
TI  - Anatomical variations of the lateral nasal wall and paranasal sinuses: A CT study
      for endoscopic sinus surgery (ESS) in Thai patients.
AB  - Computerized tomography (CT) of the paranasal sinuses is usually required prior
      to endoscopic sinus surgery. CT demonstrates both the extent of disease(s) and
      the anatomical variations that may predispose to rhinosinusitis and nearby vital
      structures that iatrogenic damage can be avoided. The authors retrospectively
      reviewed 88 CT scans of paranasal sinuses and orbits, performed at Srinagarind
      Hospital between January 1995 and February 1997. Only adult patients were
      included. The study showed the presence of frontal sinuses in 88% of cases (95%CI
      82.3-92.5%), agger nasi cells in 92% (95%CI 87-95.6%), concha bullosa in 34%
      (95%CI27.1-41.6%), Haller's cell in 24% (95%CI 17.8-30.9%), Onodi cell in 25%
      (95%CI 19.8-32.1%), dehiscence of the internal carotid artery in 10.2% (95%CI 6.2
      15.7%) and the optic canal in the sphenoid sinus in 18.2% (95%CI 12.8-24.7%). The
      most common olfactory fossa was type II. Haller's cell was a coincident finding
      not a risk factor for maxillary rhinosinusitis. Concha bullosa was a non
      statistically significant, risk factor for maxillary rhinosinustis.

PMID- 16083217
TI  - Flow cytometric crossmatch for kidney transplantation.
AB  - Serum samples from 49 patients with panel reactive antibodies of greater than 15%
      and 17 patients who have related donor pairs were collected at the Department of
      Transfusion Medicine, Faculty of Medicine Siriraj Hospital. Crossmatching was
      performed by three methods, flow cytometry crossmatch (FCXM), the standard
      National Institutes of Health (NIH), and the antihuman globulin (AHG)
      microlymphocytotoxicity. 28.9% Spell out of both T- and B-cell crossmatch was
      positive by FCXM and negative by NIH and AHG. When the T-cell and B-cell
      crossmatches were negative by FCXM, they were negative by both NIH- and AHG
      method. There was significant difference of the crossmatch result between FCXM
      and NIH and between FCXM and AHG (p < 0.0001). In addition, FCXM was about 4-16
      and 8-32 times more sensitive than AHG- and NIH method, respectively. In
      conclusion, the result of FCXM is clear and this method is more sensitive than
      NIH- and AHG method FCXM should be used together with the NIH- and AHG method for
      kidney transplantation.

PMID- 16083218
TI  - Depth of endotracheal tubes in Thai adult patients.
AB  - OBJECTIVE: To predict the proper depth of placement of endotracheal tubes, oral
      and nasal. MATERIAL AND METHOD: This was a prospective study of 100 patients who
      underwent general anesthesia with oral endotracheal intubation. The cuff of the
      endotracheal tube was placed 2 cm below the vocal cords. The positions of the
      endotracheal tube tip and the airway distances of the patients were measured by
      fiberoptic bronchoscope; OC = the distance from the right upper canine to the
      vocal cords, NC = the distance from the right external naris to the vocal cords
      and T = the distance from the vocal cords to the carina. The correlation between
      the airway distances and patient's factors were analyzed. The proper depth of
      placement of the endotracheal tube was calculated with the formula OTT = OC + T
      2, nasal endotracheal tube NTT = NC + T-2. RESULTS: The mean distance from the
      endotracheal tube tip to the carina was 3.0 +/- 1.48 cm (ranged 0.7 - 7.5 cm).
      The distance from the endotracheal tube tip to the carina of 86 from 100 patients
      was more than 2 cm. The mean OC was 9.79 +/- 1.27 cm. The mean NC was 15.00 +/-
      0.84 cm. The mean T were 13.03 +/- 1.48 cm in males and 11.63 +/- 1.25 cm in
      females and it also related to the height of the person (Pearson correlation =
      0.557, p value < 0.05). These distances did not relate to gender. CONCLUSION: The
      predicted formula of the depth of the endotracheal tube as "Chula formula"; OTT =
      4 + (Ht/10) cm (The distance from the right upper canine to the point which is 2
      cm above the carina) NTT = 9 + (Ht/10) cm (The distance from the right external
      naris to the point which is 2 cm above the carina).

PMID- 16083219
TI  - Association of the Epstein-Barr viruses with Hodgkin lymphoma: an analysis of
      pediatric cases in Thailand.
AB  - An investigation as to whether any association of pediatric HL in Thailand was
      likely to be EBV positive was performed on formalin-fixed paraffin embedded
      tissue sections using in situ hybridization for EBV encoded RNA (EBER) technique.
      The analysis was performed on 15 cases. They were 11 male and 4 female cases. The
      subtypes of HL according to WHO classification were nodular lymphocyte
      predominance in 1 (6.6%), nodular sclerosis in 4 (26.6%), mixed cellularity in 9
      (60%) and lymphocyte depletion in 1 (6.6%). EBV encoded RNA by in situ
      hybridization was demonstrated in 92.8% of classic HL: 3 of 4 (75%) with nodular
      sclerosis; 9 of the 9 with mixed cellularity (100%) and 1 of 1 (100%) with
      lymphocyte depletion. Case of nodular lymphocyte predominance was negative for
      EBV, CD 15 CD 30 and positive for CD 20. CD 15 and CD 30 were positive in 78.6%
      and 85% respectively for classic HL. Our results suggest a strong association of
      EBV with pediatric classic HL (92.3%) particularly the mixed cellularity subtype
      (100%). The result confirms the male predominance in pediatric HL. Mixed
      cellularity is the most common subtype of HL in our series (60%).

PMID- 16083220
TI  - Correlation of HBV and HCV with CH, LC, HCC in liver biopsied tissue at Rajavithi
      Hospital.
AB  - Retrospective study in Clinicopathology of 66 surgical liver tissue from adult
      Thai patients admitted at Rajavithi Hospital, in Bangkok, during December 2002
      September 2003 (10 month periods). The main purposes are: 1) To find the
      correlation of HBV, HCV with CH, LC, HCC. 2) To compare the correlation of
      Hepatocyte, AFP, CEA (IHC) in malignant cells, which one is the best usage to
      confirm the diagnosis of HCC in both primary and metastasis. 3) To review the
      clinicopathology of all these 66 liver samples. The results were significant
      correlation of HBsAg (serology) with HCC (p = 0.010), and also significant
      correlation of HBsAg (IHC in liver tissue) with CH, LC (p = 0.038, 0.021
      respectively). Although no significant correlation (p > 0.05) of HCV (positive
      anti HCV) with CH, LC, HCC; the causes due to the small sample sizes and short
      period study are possibly bias factors. The authors concluded that Hepatocyte or
      Hep-Par I is the best immunocellular marker for malignant liver cells both in
      primary and metastasis (p < 0.001). The AFP, CEA show no correlation (p = 0.999,
      0.670). The authors found other interesting non-viral related liver disease,
      common, uncommon, tumor and tumor-like (pseudotumor) lesions in the liver from
      the present study. The results of significant correlation of HBV (HBsAg) with CH,
      LC, HCC is one good evidence to further support The National HBV Vaccine Program
      for the uninfected population, which has been sponsored by the Thai Government,
      The Ministry of Public Health since 1992 and be one of the best and successful
      Thai Public-Health Policy.

PMID- 16083221
TI  - Determination of reference intervals of HbA1C (DCCT/NGSP) and HbA1C (IFCC) in
      adults.
AB  - OBJECTIVE: To establish HbA1C reference intervals according to DCCT/NGSP (HbA1C
      DCCT/NGSP) and IFCC (HbA1C IFCC) in adults. STUDY DESIGN: The study was a
      descriptive study. MATERIAL AND METHOD: The study was done in 144 subjects, with
      99 males and 45 females, aged between 19 to 78 years old. All subjects had normal
      vital signs, physical examination, chest X-ray. Subjects who had hyperglycemia,
      renal problem, liver problem, anemia, and/or hemoglobinopathy were excluded from
      the present study. RESULTS: Reference intervals of HbA1C (DCCT/NGSP) is 5.47%
      (4.79-6.15) and HbA1C (IFCC) is 3.66% (2.88-4.44). The authors also found very
      high correlation between HbA1C (DCCT/NGSP) and HbA1C (IFCC) of total, male,
      female, < 35 years old, and > or = 35 years old, r = 0.9995, 09997, 0.9992,
      0.9988, and 0.9999, respectively. CONCLUSION: The authors found that HbA1C
      (DCCT/NGSP) and HbA1C (IFCC) are not affected by sex but are influenced
      significantly by age group. Since HbA1C (IFCC) will be widely used in routine
      diabetes management, the authors recommend all laboratories provide the results
      of HbA1C in both DCCT/NGSP and IFCC methods during this interim period.

PMID- 16083222
TI  - Mucocutaneous findings in febrile neutropenic children with acute leukemias.
AB  - Febrile neutropenia is common in children with leukemia. Mucous membrane and skin
      are most common portals of entry for microorganisms in these patients. The aim of
      the present study was to find the prevalence of mucocutaneous findings infebrile
      neutropenic leukemic children. The authors prospectively examined children with
      fever with neutropenia in acute leukemia, aged 1-15 years, who were admitted to
      the Department of Pediatrics, King Chulalongkorn Memorial Hospital, between
      September 2000 and August 2001. During the study period, 46 children had 116
      admissions, 51 of which were due to febrile neutropenia. Their cancer diagnoses
      were ALL (76%) and ANLL (24%). The prevalence of mucocutaneous findings was 86%
      (61% were from infections, 22% from mucositis and 4% from chemical phlebitis).
      Other detected sites of infection were lower respiratory tract (36%), urinary
      tract (32%), upper respiratory tract (11%), septicemia (11%) and unidentified
      (35%). Thirty-four percent of the patients had more than one site of infection.
      Gram-negative septicemia was the most common infection (15cases/71%) followed by
      gram positive (4cases/19%) and candida (2cases/10%). The prevalence of infection
      was found in severe neutropenia (absolute neutrophil count, ANC less than 500
      cell/cu mm), moderate neutropenia (ANC, 500-1000 cell/cu mm) and mild neutropenia
      (ANC, 1001-1500 cell/cu mm) was 72%, 9% and 5%, respectively. Infection in
      patients in the severe neutropenia group was significantly more common than in
      moderate mild neutropenia groups (p < 0.01). Seven patients (15%) died, all of
      them had severe and prolonged neutropenia, for more than 7 days. Daily physical
      examination of skin and mucous membrane are suggested for proper and prompt
      diagnosis and treatment of febrile neutropenic children with acute leukemia to
      reduce mortality and morbidity in these patients. A Guideline for the use of
      antimicrobial agents in neutropenic patients with acute leukemia is proposed In
      conclusion, infection was commonly found in severe neutropenia. Mucocutaneous
      infection was the most common site of infection infebrile neutropenia in children
      with leukemia.

PMID- 16083223
TI  - Dyslipidemia in Thai rural adults.
AB  - The present study aimed to determine the prevalence of dyslipidemia in adults in
      a rural area of Thailand. Random sampling was conducted in 443 volunteers, 187
      males and 256 females, aged > or = 35 years in Chachoengsao Province. After a 12
      hour fast, the blood was drawn for the analysis of total cholesterol,
      triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL)
      cholesterol. Mean serum lipids of cholesterol, LDL cholesterol, HDL cholesterol
      and triglycerides were 207.79 +/- 46.98, 117.26 +/- 36.59, 50.53 +/- 2.14 and
      201.21 +/- 131.07 mg/dL, respectively. Nineteen percent of them had cholesterol >
      or = 240 mg/dL and 10% had LDL cholesterol > or = 160 mg/dL. Seven percent had
      HDL cholesterol < or = 35 mg/dL. However, LDL/HDL cholesterol ratios > 5, were
      found in only 0.9%. In conclusion, the prevalence of dyslipidemia was high in
      rural Thai adults. Further surveillance in this population is essential in
      verifying the impact of dyslipidemia as a risk of cardiovascular disease in rural
      Thai adults.

PMID- 16083224
TI  - Increasing risks of becoming obese after 6 years in primary school: comparing the
      relative risks among some schools in Bangkok, Saraburi and Sakolnakorn.
AB  - The authors carried out a retrospectively study of bodyweights of primary-school
      children from Grade I to Grade VI in 4 schools from Bangkok, one school from
      Saraburi and data of school children from a district in Sakolnakorn with a six
      year follow-up period. In the cohort there were 437 children from Bangkok, 225
      children from Saraburi and 633 children from Sakolnakorn. Initial data show that
      prevalence of obesity at grade I in schools from Bangkok, Saraburi and
      Sakolnakorn were 16%, 23% and 4%, respectively. However, when these children were
      in grade VI, the prevalence of obesity increased to 31%, 30% and 9%,
      respectively. Relative risks of becoming obese at grade VI in children who were
      overweight and obese at grade I are 3 and 5 fold in Bangkok, 2 and 3 fold in
      Saraburi, 6 and 12 fold in Sakolnakorn, respectively. The present study shows
      that prevalence of obesity increased at quite dramatic rates during the primary
      school period in these study groups.

PMID- 16083225
TI  - Cardiac CT angiography: comprehensive assessment of patient suspected coronary
      artery disease.
AB  - Coronary artery disease is the leading cause of mortality and morbidity
      worldwide. Although coronary angiography is currently a gold standard for
      diagnosis of coronary artery disease, some patients are of concern regarding
      small but not negligible risk of complications and discomfort of the procedure.
      In recent years, cardiac computerized tomographic angiography (CTA) is an
      attractive non-invasive modality for evaluation of chest pain in patients
      suspected to have coronary artery disease. The authors report a 61 year-old-man
      with a history of hypertension and hypercholesterolemia who presented with
      exertional angina pectoris for 3 weeks. Cardiac CTA was performed and revealed a
      severely stenotic lesion at the proximal left anterior descending coronary artery
      (LAD) with left ventricular ejection fraction of 53% and hypokinesia of
      anteroseptal and apical wall. The patient then was planned and underwent
      percutaneous coronary interventional procedure. This case highlights the utility
      of comprehensive information from cardiac CTA as a modality for coronary
      interventional procedure planning.

PMID- 16083226
TI  - Enteric fever-like illness caused by infection with citrobacter amalonaticus.
AB  - 'Enteric fever' is a potentially fatal, severe systemic disease, which is
      encountered worldwide. Traditionally, enteric fever refers to a bacteremic
      illness caused by members of certain Salmonella serotypes, notably: Salmonella
      typhi, a Gram-negative bacterium, and to a lesser extent, Salmonella paratyphi A,
      B and C. In addition, other non-salmonella organisms may produce a syndrome
      clinically indistinguishable from "enteric fever". Brucella sp., Campylobacter
      sp., Edwardsiella tarda, Enterobacter Cloacae, Escherichia coli, Klebsiella
      pneumoniae, Providencia alcalifaciens, Pseudomonas sp., Serratia marcescens,
      Francisella sp. and Yersinia pp have been identified in enteric fever This is, to
      the best of the authors' knowledge, the first case of Citrobacter to be reported
      presenting as enteric fever in a normal host in Thailand.

PMID- 16083227
TI  - Brunner's gland adenoma: a report of two cases.
AB  - Brunner 's gland adenoma is a very rare benign tumor of the duodenum. Only two
      cases of the adenoma have been in the file of the surgical pathology unit of
      Ramathibodi Hospital since 1992 and presented in this communication. The tumor is
      capable of producing a variety of clinical manifestations. Presently, endoscopic
      study plays an important role in both detection and diagnostic biopsy. Local
      excision, either by endoscopy or surgery is the main treatment in symptomatic
      cases. Ductal malignancy on top of Brunner's gland adenoma was described in one
      from estimated 200 recorded cases in the English literature since 1835.

PMID- 16083228
TI  - Translaryngeal retrograde wire-guided fiberoptic intubation for difficult airway:
      a case report.
AB  - The authors describe the special tracheal intubation technique used in two
      patients with a difficult airway. These are the translaryngeal retrograde wire
      guided and fiberoptic intubation. The authors show how to use both to facilitate
      intubation. The authors modified the technique by passing a guide-wire in a
      retrograde manner from the trachea to the nose and then a fiberoptic laryngoscope
      within the endotracheal tube over the wire. The technique can be applied for use
      in any difficult airway situation.

PMID- 16083229
TI  - Primary peritoneal adenosarcoma with stromal overgrowth and fetal type cartilage:
      a case report and literature review.
AB  - Primary peritoneal adenosarcoma with sarcomatous overgrowth and fetal-type
      cartilage presented in a 48-year-old female patient is described. The tumor seems
      likely to have derived from the pelvic peritoneum, wheareas the uterus, ovaries
      and tubes were uninvolved. It was composed of benign-appearing glands and a
      sarcomatous component showing cartilaginous differentiation. The extrauterine
      adenosarcomas were reported in other sites, e.g. cervix, ovary, fallopian tube,
      bladder, and peritoneum. This case was the ninth case of the primary peritoneal
      adenosarcoma in the English literature and the first report in Thailand.

PMID- 16083230
TI  - Wernicke's encephalopathy: report of a case.
AB  - A case of Wernicke's encephalopathy is reported. A 53-year-old alcoholic man was
      presented with acute confusion, upward gaze palsy of the left eye and gait ataxia
      for 5 days. The typical findings upon MRI of the brain showed multiple,
      scattered, small non-enhanced low signal intensity on T1WI, high signal intensity
      on T2WI involving at bilateral basal ganglias, and thalami, midbrain, pons, and
      periventricular regions with evidence of atrophic changes of brain and the
      mamillary bodies. After treatment with intravenous thiamine 100 mg/day, the left
      upward gaze palsy was fully recovered at the 8th day of treatment. The mental
      status and gait ataxia gradually improved.

PMID- 16083231
TI  - [Rabies diagnosis in human].
AB  - Rabies diagnosis in humans can be made by obtaining a history of exposure
      particularly to an animal bite, clinical symptoms and signs, neuroimaging such as
      magnetic resonance imaging (MRI) and laboratory testing. Although diagnosis made
      by clinical grounds alone can be useful, this can only be limited to furious
      rabies. Owing to the fact that there is more than one form of rabies (furious,
      paralytic and atypical rabies) relying on only clinical diagnosis will
      undoubtedly lead to under reporting. The nonclassic or atypical rabies presents
      with a non specific pattern lacking pathognomomic signs as found in classic forms
      (furious and paralytic). A diagnosis of rabies should be considered in any
      patient who presents with encephalopathy of unknown cause. Diagnosis of rabies
      requires laboratory confirmation. MRI pattern may differentiate rabies from other
      viral encephalitides. Laboratory diagnosis can be used for confirmation by
      demonstration of viral proteins or its genomic RNA. The nucleic acid
      amplification method is often used as a diagnostic test due to its good
      sensitivity and specificity and can be applied to wide varieties of specimens.
      Accurate data on rabies statistics contribute to the success in control and
      prevention of rabies.

PMID- 16083232
TI  - Medical ethics for senior medical doctors (Episode II).

PMID- 16083233
TI  - The neurology of HIV infection--a review of the literature.
AB  - BACKGROUND: The nervous system is widely involved in the course of infection with
      the human immunodeficiency virus (HIV). The manifestation may be a direct effect
      of the virus, the result of opportunistic infections or secondary malignancies,
      or a result of the therapy of various aspects of the disease. This review looks
      at these neurological consequences of HIV infection. METHODS: The review was
      sourced mainly by Medline search using the search terms HIV, AIDS and neurology.
      Relevant journals were subsequently studied. RESULTS: The major neurological
      manifestations of HIV infection are toxoplasmosis, cryptococcal meningitis, AIDS
      dementia complex, primary lymphoma, tuberculosis, progressive multifocal
      leukoencephalopathy, herpes zoster, Bells palsy, peripheral neuropathy, and
      vacuolar myelopathy. The overall effect of these is the acceleration of
      progression of the disease. About 30% of the mortality in HIV infection is
      attributed to neurological diseases. CONCLUSION: The nervous system is
      significantly affected in HIV infection and the impact on morbidity and mortality
      is profound. All effort should be made to ensure early recognition and
      amelioration of the various nervous systems complications of HIV infection.

PMID- 16083234
TI  - Prevalence of HIV--related oral lesions in Nigerian women.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection affects an increasing
      number of women throughout the world. Oral lesions are among the earliest
      clinical manifestations of HIV infection and are associated with its progression.
      We describe the oral manifestations of HIV/AIDS in Nigerian women and its
      clinical correlates. METHODS: Nigerian women with HIV/AIDS were examined for the
      presence of oral lesions attributable to HIV/AIDS. These lesions were diagnosed
      clinically, according to the criteria established by the European Community
      Clearinghouse (ECC) on oral problems related to HIV infection. RESULTS: Two
      hundred and sixty-nine seropositive women were examined with a range of 17-60
      years (mean of 32.4 years < 8.09). The age group of 21 30 years was the worst
      affected (n = 125, 46.5%). Of these patients, 109 (40.5%) were married, 67
      (24.9%) were single while 47 (17.5%) had multiple sexual partners. One hundred
      and eighteen (43.9%) had at least an oral lesion associated with HIV/AIDS. The
      most common was oral candidiasis, which was present in 98 (36.4%) patients.
      Pseudomembraneous candidiasis (n = 66, 24.5%) and angular cheilitis (n = 23,
      8.6%) were the commonest variants seen. The former was the only lesion
      significantly associated with the clinical stage of the infection (p = 0.002)
      while necrotizing gingivitis, linear gingival erythema and angular cheilitis were
      associated with the age of the patients (p < 0.05). CONCLUSION: Oral
      manifestations are common features of HIV infection among Nigerian women. Oral
      candidiasis (OC) was the most notable oral lesion associated with HIV/AIDS. It
      may be a useful clinical indicator of early immune dysfunction mediated by HIV.

PMID- 16083235
TI  - Growth pattern of exclusively breastfed infants in the first six months of life:
      a study of babies delivered at the University of Port Harcourt Teaching Hospital,
      Rivers State, Nigeria.
AB  - BACKGROUND: Some authors demonstrate that exclusively breastfed infants have
      growth patterns comparable with the NCHS standards while others conclude that
      exclusively breastfed infants grow slower. These conflicting results informed the
      need for this study to aid the paediatricians and health workers to justify or
      condemn the recommendation of exclusive breastfeeding for six months. This was a
      prospective longitudinal study carried out to determine the growth pattern of
      exclusively breastfed infants in the first 6 months of life and compare them with
      the International, National Centre for Health Statistics (NCHS/WHO) reference and
      the Local, Janes' Elite Standards. METHODS: Using weight, length and occipito
      frontal circumference as indices, 530 infants were recruited consecutively by
      convenience sampling over 17 months. Measurements were taken at birth, 2 weeks, 6
      weeks, 2 months and subsequently monthly until the end of the 6th month. RESULTS:
      The exclusively breastfed infants doubled their birth weights at 3 months. The
      mean weight, OFC and length gains were maximal at 2 months, 2 weeks and 2 months
      respectively. The growth of exclusively breastfed infants compared favourably
      with the NCHS/WHO reference group and also compared favourably with the Janes'
      'Elite' reference group. CONCLUSION: It is concluded that the growth in weight,
      length and OFC of exclusively breastfed infants appears adequate for the first 6
      months of life.

PMID- 16083237
TI  - Sociodemographic characteristics of anaemic gravidae at booking: a preliminary
      study at Llesha, Western Nigeria.
AB  - BACKGROUND: Anaemia in pregnancy is a significant cause of direct and indirect
      morbidity and mortality to both the pregnant mother and her fetus. The prevalence
      however remains undetermined in many parts of Africa. The study aims at
      determining the prevalence of anaemia and sociodemographic characteristics of
      anaemic pregnant women in a Nigerian tertiary obstetric care centre. METHODS: A
      cross-sectional study involving all pregnant women that registered for ante-natal
      care between 1st January 2001 and 30th of June 2001 in Wesley Guild Hospital Unit
      of Obafemi Awolowo University Teaching Hospitals Complex, Ile-lfe. RESULTS:
      Prevalence of anaemia among the pregnant women during the period of study was
      62.2%. Two percent of the women had severe anaemia. Parity and gestational age at
      booking significantly influenced the prevalence of anaemia. CONCLUSION:
      Prevalence of anaemia among pregnant women in developing world is still
      unacceptably high, and it calls for improvement in standard of living for our
      pregnant women.

PMID- 16083236
TI  - Awareness, attitude and practice of contraception among secondary school girls in
      Calabar, Nigeria.
AB  - BACKGROUND: Adolescents are disposed to unprotected sexual activity and as a
      consequence, there is an increasing incidence of unwanted pregnancy among
      adolescent school girls in Nigeria. This study was carried out to assess the
      awareness, attitude and use of contraceptives among secondary school girls in
      Calabar, Nigeria and to determine how attitude affects its use. METHODS: Data was
      obtained using self administered semi-structured questionnaires distributed to
      480 secondary school girls out of which 450 were properly filled and returned.
      These were analysed using percentages and chi-square was used to test for
      significance. RESULTS: The study revealed that contraceptive awareness was high.
      The main sources of contraceptive information were books/magazines (37%) and
      friends (26%). Three hundred and thirty-three (74%) girls had a negative attitude
      (misconceptions) towards contraceptives, while 117 (26%) girls said
      contraceptives were essential/useful. Sixty-six girls (14.7%) admitted that they
      were currently sexually active and 42 (9.3%) of them used contraceptives. There
      was a statistically significant association between positive attitude/beliefs and
      use of contraceptives (P < 0.05). CONCLUSION: We recommend the provision of
      accurate contraceptive information to dispel these misconceptions and the
      establishment of adolescent reproductive health services which should be strictly
      confidential to encourage acceptability and optimum utilization.

PMID- 16083238
TI  - Plasma lipids during pregnancy in women in Port Harcourt, Nigeria.
AB  - BACKGROUND: Pregnancy in Caucasian women is known to be associated with
      hyperlipidaemia. In a background of poor socio-economic conditions, early
      marriage, poor acceptance of contraceptives, poor spacing of pregnancies, high
      fertility rate and poor maternal and child health indices, this study was
      designed to investigate the pattern and degree of serum lipid changes during
      pregnancy in black African women in Port Harcourt, Nigeria. METHODS: Two hundred
      and thirty apparently healthy pregnant women at different stages of pregnancy and
      51 non-pregnant control subjects of comparable age, height, and parity were
      serially recruited into the study. Plasma total cholesterol (TCHOL), LDL
      Cholesterol (LDL-CHOL), HDL-Cholesterol (HDL-CHOL) and triglycerides (TG) were
      estimated for all study subjects and mean plasma lipid levels calculated for
      first, second and third trimesters of pregnancy. RESULTS: There was an increase
      in the mean concentration of plasma TCHOL, HDL-CHOL, and TG and a decrease in LDL
      CHOL in the pregnant subjects as compared to the non-pregnant control subjects.
      Mean TCHOL, HDL-CHOL, LDL-CHOL and Triglycerides tended to increase with
      increasing gestational age. CONCLUSION: The results show that pregnancy in black
      Nigerian women is associated with hyperlipidaemia. The implications of this
      finding are discussed.

PMID- 16083239
TI  - Characteristics of colorectal carcinoma in Kano, Nigeria: an analysis of 50
      cases.
AB  - BACKGROUND: Several recent publications have shown a rising incidence with high
      morbidity and mortality of colorectal cancer amongst blacks. The aim of this
      study was to determine the epidemiological profile of the colorectal carcinoma in
      our hospital, a major referral centre in northwestern Nigeria. METHODOLOGY: A
      retrospective analysis of all histologically proven cases of colorectal carcinoma
      was performed from January 1999 to December 2002. RESULTS: Fifty patients were
      managed during the study period with an average presentation of 12.5 cases per
      year. There were 36 (72%) males and 14 (28%) females (M:F = 2.5 to 1). The mean
      age at presentation was 42.9 years with 36 patients (72%) below 50 years of age.
      Carcinoma of the colon occurred in 22 (44%) patients and rectal carcinoma in 28
      (56%) patients. Twenty (71.4%) of the 28 rectal cancers were digitally palpable.
      Thirty-eight (92.7%) patients had palliative resection, while 3 (7.3%) had
      curative resection. Adenocarcinoma was the only histologic type, with 15 (30%)
      cases of the mucinous variety. CONCLUSION: There is need to increase awareness
      through public education about this malignancy and its management. Any adult with
      complaints of vague abdominal pain, blood or mucus in the stool or features of
      haemorrhoids which may herald the onset of colorectal cancer should be adequately
      investigated with digital rectal examination (DRE) and proctosigmoidoscopy and
      barium enema where appropriate.

PMID- 16083240
TI  - Pathological study of colorectal carcinoma in adult Nigerians: a study of 45
      cases.
AB  - BACKGROUND: A 12-year (1st Jan. 1990-31st Dec. 2001) retrospective study of 45
      colorectal carcinomas was carried out the in University of Port Harcourt Teaching
      Hospital (UPTH) based on age, sex, clinical presentation, anatomical sites,
      histological types and clinical stages. METHODS: All the histological slides from
      surgical specimen obtained from the large intestine and diagnosed as colorectal
      carcinoma were reviewed in Anatomical Pathology Department of UPTH, Port
      Harcourt. The age, sex, sites and histological types were extracted from the
      request forms and reports while the clinical presentation and staging were
      obtained from the case notes. RESULTS: A total of 34 (75.6%) and 11 (24.4%)
      occurred in males and females respectively, giving a sex ratio of 3:1. The least
      age of occurrence was a 22 year old male and the oldest was a 82 year old male.
      The highest frequency (28.9%) occurred in the age group 50-59 years which is a
      decade earlier than the Caucasians. Majority of our patients (33.3%) presented
      with either diarrhoea or constipation (altered bowel habit). The commonest site
      of this cancer is the rectum and the least occurred in the transverse colon. Most
      of our patients presented with advanced cancer of stage IV & III of TNM
      classification (D and C of Astler-Coller System). The tumours were also
      histologicially graded into well moderately and undifferentiated type.
      CONCLUSION: Colorectal carcinoma is one of commonest malignancies that occurs in
      young and middle aged in this environment. Patients present when the tumour is in
      an advanced stage hence poorer prognosis and the ages of the patents is about 10
      years earlier than that of Caucasians.

PMID- 16083241
TI  - The bacteriology of diabetic foot ulcers in Port Harcourt, Nigeria.
AB  - BACKGROUND: Diabetic foot ulcer and/or gangrene is a common cause of morbidity
      and mortality in Nigeria. The lesions are usually infected and early treatment of
      the infection will reduce the associated problems. The study was carried out to
      determine the common bacteriological flora of diabetic foot ulcers in Port
      Harcourt. The antimicrobial sensitivity pattern of the isolates was determined to
      enhance possible empirical treatment. METHODS: Deep wound swabs were collected
      from 60 consecutive diabetic patients admitted with foot ulcers and/or gangrene
      into the medical wards of the University of Port Harcourt Teaching Hospital from
      January 2001 to April 2002. The bacteriological isolation and antimicrobial
      sensitivity tests of the isolates was carried out by standard microbiological
      methods. RESULTS: Aerobes and anaerobes constituted 95.4% and 4.6% of the total
      bacterial isolates respectively. Staphylococcus aureus was the commonest
      bacterial isolate; it was cultured from 32 (56.1%) of infected patients and
      constituted 24.4% of the total isolate. The mean bacterial isolate per patient
      infected was 2.3. The aerobic isolates showed significant sensitivity to
      ciprofloxacin (78.4%), pefloxacine (71.2%), ceftazidime (73.6%) and cefuroxime
      (69.6%). All the anaerobic isolates were sensitive to metronidazole and
      clindamycin. CONCLUSION: Infections of diabetic foot ulcers are usually
      polymicrobial. From the in vitro antimicrobial susceptibility pattern of the
      bacterial isolates, diabetic patients presenting with foot ulcers and/or gangrene
      could be commenced empirically on a combination of clindamycin or metronidazole
      and either a fluoroquinolone (ciprofloxacin or pefloxacine) or a second or third
      generation cephalosporin (e.g. cefuroxime or ceftazidime).

PMID- 16083242
TI  - Combined effects of temperature changes and radiation absorption on living
      tissue.
AB  - BACKGROUND: The need for the development of criteria for the referral of patients
      for radiographic examinations, especially in the face of the results of separate
      studies on temperature and radiation effects, formed the background to this
      study. The aim of this study is to determine the possible consequences of low
      dose radiation to living tissue in the presence of elevated temperatures, with a
      view to developing referral criteria for patients scheduled for radiodiagnostic
      examinations. METHOD: A two part procedure in the form of x-irradiation of water
      phantom at temperatures ranging from 25 and 45 degrees Celsius, to assess
      absorbed dose with temperature variation, as well as histological study of living
      tissue extracted from the skin and lungs of experimental animals, exposed to x
      radiation at kilovoltage range between 50 and 90 and temperature values between
      25 and 45 degrees Celsius. RESULTS: Results showed increased radiation absorption
      with rising temperature in the studied samples suggesting that radiation
      absorption and therefore effects, may be functions of the temperature of the
      absorbing medium, being more pronounced at higher temperatures, even at constant
      exposure. CONCLUSION: A combination of elevated temperatures and x-radiation,
      even at diagnostic exposures doses, may not be safe for patients, especially in
      paediatric radiography patients presenting with body temperatures in the
      neighborhood of 40 degrees Celsius. The application of this as a radiation
      protection measure in the use of ionizing radiation is recommended, especially
      where highly dividing tissue is involved.

PMID- 16083243
TI  - An evaluation of the Beckman-Coulter AcT 3-part differential haematology analyzer
      in a tertiary hospital laboratory.
AB  - BACKGROUND: The Beckman-Coulter AcT differential haematology analyzer was
      evaluated to compare its haemoglobin (HGB), haematocrit (HCT), platelet (PLT),
      total white cell count (WBC) values and differential leukocyte count (DLC) with
      the reference manual methods used in our laboratory. METHODS: Samples drawn into
      5 millilitres k3 EDTA bottles were selected on a random basis from our routine
      workload over a 4-week period. Fifty patient samples were analyzed on the AcT
      diff Coulter analyzer. The same patient samples were then reanalyzed using the
      reference manual method for comparison. Haemoglobin (cyanmethhaemoglobin method),
      haematocrit (micro-haematocrit method), total WBC (Turk's Method), platelet
      (Brecker-Cronkite method) were carried out and blood films were stained with
      leishman stain, and a 100-cell manual differential count was performed under oil
      immersion. RESULTS: The Beckman Coulter AcT 3 diff haematology analyzer was shown
      to have excellent precision and accuracy for HGB and HCT with coefficient of
      correlation > 0.974. WBC and PLT had low coefficient of correlation of 0.208 and
      0.034 respectively. The DLC parameters was shown to have good correlation
      coefficients for neutrophils > 0.876 and lymphocytes > 0.84. Monocytes showed a
      low correlation of 0.082 without clinical significance. CONCLUSION: The clinical
      sensitivity of the instrument in relation to the population evaluated was good.
      In all, the study results indicate that the AcT 3-part haematology analyzer could
      improve the overall laboratory productivity with flagged abnormal results being
      confirmed by the manual reference method.

PMID- 16083244
TI  - Soft tissue sarcomas in the Niger Delta Region of Nigeria (a referral hospital's
      study).
AB  - BACKGROUND: Soft tissue sarcomas are rare tumours in this environment. Recently,
      an upsurge in frequency was noticed that called for attention. The aim of this
      study is to study soft tissue sarcomas based on age, sex of patients, tumour
      sites and histologic types. METHODOLOGY: A 14 year retrospective study in
      University of Port Harcourt Teaching Hospital (UPTH) Port Harcourt. Histological
      slides previously processed and stained with hematoxylin and eosin stains (H & E)
      were reviewed and re-evaluated. Special stains were also used for proper
      diagnosis of some tumours. The tumours were classified based on World Health
      Organization (WHO) classification of soft tissue tumours. RESULTS: Only 66 soft
      tissue sarcomas were used for this study which accounted for 2.8% of the total
      malignancies diagnosed during the period under review. The youngest was a 3 year
      old girl while the eldest was a 76 year old female. A total of 38 and 28 tumours
      were diagnosed in males and females respectively, giving a sex ratio of 1.4:1.
      Rhabdomyosarcoma was most frequent (39.4%) while the least was leiomyosarcoma
      (1.5%). These tumours are more frequent in the under 20 years (22.7%) and least
      in 70 years and above (7.6%). The lower limb was most affected (36.4%) while the
      least was the retroperitoneum (6.1%). The commonest predilection sites vary with
      different classes of these group malignancies. CONCLUSION: Soft tissue
      malignancies are globally uncommon but they constituted an integral part of
      malignant tumours causing serious morbidity and mortality in this environment.
      The recent upsurge noticed necessitated the need for regional studies in Nigeria
      in order to come up with a national epidemiologic data of these malignancies.

PMID- 16083245
TI  - Job satisfaction among primary health care workers in three selected local
      government areas in southwest Nigeria.
AB  - BACKGROUND: The primary health care system in Nigeria has been impaired by lack
      of dedicated workers who are willing to work in the rural areas. This study was
      carried out to examine factors that enhance job satisfaction among health workers
      in the primary health care system in Nigeria. METHOD: The study is a cross
      sectional descriptive study conducted in May 2002. The respondents were selected
      from three local government areas in southwest Nigeria by multistage sampling
      technique. A standardized structured pre-coded close-ended self-administered
      questionnaire to collect relevant information on their socio-demographic
      characteristics and extent of job satisfaction of respondents. RESULT: A total of
      125 health workers were interviewed in all. The mean score on job satisfaction
      was 26.15 out of the total possible score of 49. There was no statistically
      significant relationship in job satisfaction among the various cadres of health
      workers considered (p = 0.824). A larger proportion (66.4%) of the health workers
      were involved with the community based preventive services when compared with the
      health centre based curative care 33.4% (p < 0.05), there is however no
      significant difference in satisfaction between this two groups of personnel (p =
      0.133). Age and marital status were found to be statistically significant in
      relation to job satisfaction (p = 0.000 and 0.034 respectively). CONCLUSION: The
      study shows no significant difference in job satisfaction among the various
      cadres of health workers in southwest Nigeria. However age and marital status
      were found to be significant factors influencing job satisfaction among the
      primary health care workers in Nigeria.

PMID- 16083246
TI  - Computing knowledge, attitude and skills among healthcare professionals in Aminu
      Kano Teaching Hospital, Nigeria.
AB  - BACKGROUND: Health care professionals can no longer ignore the application of
      information technology to health care. This study was carried out to assess
      computing knowledge, attitude and skills among health care professionals and
      identify associated factors. METHODS: A cross section of 200 health care
      professionals- consisting of 64 doctors, 90 nurses, 35 laboratory scientists and
      11 pharmacists in Aminu Kano Teaching Hospital were interviewed using a pre
      tested, structured, closed-ended self-administered questionnaire. RESULTS: Only
      181 (90.5%) of the respondents returned the completed questionnaires. Twenty six
      percent of the respondents had formal computer training whereas 34.8% owned a
      personal computer. Overall, 84 (46.4%) of the respondents had good knowledge of
      computing. Specifically, 41(66.0%), 5 (50.0%), 14 (51.0%) and 24 (30.0%) of these
      were doctors, pharmacists, laboratory scientists and nurses respectively.
      Computing knowledge was highest among doctors and lowest among nurses. These
      differences were statistically significant (chi2 = 19.1 df = 3 P < 0.01). Age,
      gender, computer ownership and formal computer training significantly influenced
      computing knowledge. Most healthcare professionals 160 (88.4%) had positive
      attitude towards computing and this was significantly influenced by respondent's
      age and previous computer training. Only 41 (22.7%) of the health care
      professionals had good computing skills and this was significantly associated
      with computer ownership (P < 0.01) and formal computer training (P < 0.01).
      CONCLUSION: Half of the healthcare professionals had good computing knowledge,
      majority had a positive attitude while many were quite deficient in computer
      skills. Computer loans and in-house computing courses were recommended to prepare
      our healthcare professionals for the challenges of the information technology
      age.

PMID- 16083247
TI  - The primary health care services in Nigeria: constraints to optimal performance.
AB  - BACKGROUND: This paper examined the management of the Primary Health Care
      Services in Nigeria using both Primary and Secondary data. METHODS: The Primary
      data were generated from social survey, interviews and participant observation
      while secondary data were sourced from health institutions. Data gathered were
      analysed using quantitative and descriptive methods. RESULTS: The findings of the
      study showed a low level of interaction and coordination among tiers of
      government which resulted in poor performance of PHC at the grassroot. The
      Primary Health Care Programme was grossly underfunded which manifested in the low
      performance of the PHC delivery facilities. The research identified some
      institutional impediments such as conflicts between Local and State Governments
      resulting in a strained relationship, poor collaboration and weak linkage.
      Community participation which is a sine qua non in the attainment of the
      objectives of the programme was very low. Finally, the participation of
      international organisations like UNICEF and USAID in PHC Programme was
      responsible for most of the achievement made so far. CONCLUSION: The research
      recommended among others that the three tiers of government must relate to one
      another to ensure that a harmonious relationship exists at all times through
      official interactions on all issues that affect the three levels of government
      especially the policy formulation, implementation, and evaluation, and evaluation
      of the Primary Health care programme.

PMID- 16083248
TI  - Abdominal pregnancy: a cause of failed induction of labour.
AB  - BACKGROUND: Induction of labour is a common mode of management of intrauterine
      fetal deaths, and the process usually involves ripening of the cervix by
      traditional methods of intracervical Foley's catheter insertion or the use of
      prostaglandin preparations intravaginally. Such methods are usually very
      effective independently. The objective of this case report is to call the
      attention of practising obstetricians to the possibility of an abdominal
      pregnancy as a cause of failure to ripen the cervix and that careful re
      evaluation and use of ultrasound scan can improve diagnostic acumen with
      favorable outcome of management in such cases METHODS: The case file of the
      patient was thoroughly reviewed. A literature search on the subject of abdominal
      pregnancy using local and international journals and relevant textbooks was done
      to document the current status of the management of such cases. RESULTS: A 29
      year-old Gravida 4 para 3+0 (2 alive) presented at an estimated gestational age
      of 32 weeks with loss of fetal movement, which was suggestive of fetal death and
      was referred as such from a private hospital. A process of induction of labour
      was commenced; to ripen the cervix with intracervical Foleys catheter and
      misoprostol tablet and stimulate uterine contraction, but this was not successful
      due to failure of the cervix to ripen. This prompted further review of the
      patient with the aim of excluding the possibility of an abdominal ectopic
      pregnancy. A repeat ultrasound scan was done and this confirmed a diagnosis of
      abdominal pregnancy. The patient had laparotomy done to deliver a dead fetus and
      the placenta was removed with the right tube and ovary as they were deeply
      embedded in the placental mass. The definitive diagnosis was that of a secondary
      abdominal pregnancy. She made a satisfactory postoperative recovery and was
      discharged home. CONCLUSION: A high index of suspicion is needed to make a first
      time diagnosis of abdominal pregnancy. With timely diagnosis and appropriate
      management, the prognosis in most cases is favourable.

PMID- 16083249
TI  - Unwholesome trauma care: a cautionary note.
AB  - BACKGROUND: Trauma care requires proper training on how to diagnose life and limb
      threatening conditions. The aim of this paper is to report an extreme case of
      unwholesome practice that drained the patient physically, emotionally and
      financially. METHODS: The medical record of the patient and relevant literature
      were reviewed. RESULT: A 25-year-old commercial motorcyclist (okada) presented
      with a huge discharging leg ulcer with exposed plate and necrotic distal half of
      the right tibia on the account of uninformed treatment he received from his
      primary physician and a traditional bonesetter spanning a period of five months.
      The foot was found to be grossly deformed and insensate. Below knee amputation
      was done as salvage. CONCLUSION: Our undergraduate curriculum should change to
      expose medical students more to basic trauma care. A designated body should
      regulate activities of traditional bonesetters. The practitioners should be made
      to undergo some form of training to recognize high-risk trauma patients and the
      need for early referral.

PMID- 16083250
TI  - Fibroadenoma coexisting with infiltrating ductal carcinoma--a case report.
AB  - BACKGROUND: Fibroadenomas are benign breast tumours that are commonly diagnosed
      in young women in their 20's and early 30's. Occurrence of malignancy in the
      breasts of these women is very rare. METHOD AND RESULT: We report a case of an
      infiltrating ductal carcinoma within an otherwise benign fibroadenoma in a 23
      year-old woman. She presented with a lump, approximately 7cm in diameter, in her
      right breast. There were no palpable axillary and supra- clavicular lymph nodes.
      Excision biopsy was carried out and histopathological report showed it to be a
      fibroadenoma coexisting with infiltrating ductal carcinoma. CONCLUSION:
      Fibroadenomas are commonly diagnosed in patients in their 20's when the risk of
      developing breast cancer is extremely rare. Despite this rarity all excised
      breast lumps should be subjected to histopathological evaluation in order to
      avoid a diagnostic pitfall.

PMID- 16083251
TI  - Isolated bilateral upper lid coloboma--a case report.
AB  - BACKGROUND: Congenital upper lid colobomas may be associated with ocular and
      systemic anomalies. This paper reports an isolated bilateral upper lid coloboma.
      METHOD: A report of a case of bilateral upper lid coloboma with discussion of
      relevant literature. RESULTS: A 5-month old healthy baby girl presented with
      isolated bilateral upper lid coloboma. The coloboma was as large as two thirds of
      each upper lid with symblepharon. She had no other associated congenital
      anomalies reported by various workers. The upper lid defect in each eye was
      repaired in two stages. She had a flap from the lower lid using the lid switch
      technique and flap separation 2 weeks after the first surgery, in a combined
      surgery by a plastic surgeon and ophthalmologists. A good functional and cosmetic
      result was achieved from the treatment. The patient was discharged five days
      after the second surgery. CONCLUSION: This case shows that lid coloboma could be
      an isolated problem in a child. Early and appropriate surgical intervention is
      necessary for good visual and functional outcome.

PMID- 16083252
TI  - Hookworm infestation in a 3-month old female.
AB  - BACKGROUND: Intestinal helminthiasis is a major cause of morbidity and mortality
      in infants and children particularly in the tropics and subtropics. This report
      highlights the possibility of hookworm infestation in infancy. METHOD: A case
      report of hookworm infestation in a three-month old infant who was managed in the
      University of Port Harcourt Teaching Hospital, Port Harcourt in May 2001 for
      failure to thrive and recurrent severe anaemia. RESULT: The patient was admitted
      in the children's emergency ward with passage of dark watery stools, fever,
      excessive crying and severe anemia and was transfused twice. Stool microscopy
      revealed numerous ova of hookworm and she was treated with albendazole. Three
      days after administration of anti-helminthic, stools became formed with normal
      colour and temperature was normal. She gained weight before discharge home.
      CONCLUSION: Hookworm infestation should be suspected as a cause of severe anaemia
      in infants in communities with a high risk of infestation such as fishing port
      communities. To the best of my knowledge, symptomatic hookworm infestation in the
      first year of life has not been previously documented in Nigeria.

PMID- 16083253
TI  - Clinical photographic quiz.

PMID- 16083254
TI  - So, you want to look for biomarkers (introduction to the special biomarkers
      issue).
AB  - The burgeoning field of proteomics plays a powerful and relevant role in the
      discovery of biomarkers, which are biometric measurements that convey information
      about the biological condition of the subject being tested. Biomarkers have
      changed the manner in which we diagnose disease, monitor the effect of therapy,
      classify disease, detect toxicity, and develop new drugs. The central part that
      proteins command in both disease etiology and treatment make them prime biomarker
      candidates. Indeed, the majority of clinical tests in use today measure proteins.
      This perspective introduces the Journal of Proteome Research Special Issue on
      Proteomics and Biomarkers. It outlines the major applications of biomarkers,
      discusses the basics of statistically assessing them and considers the crucial
      choice of sample type. Central considerations of biomarker discovery and
      validation, particularly with respect to their intended clinical and research
      applications, are highlighted.

PMID- 16083255
TI  - Correcting common errors in identifying cancer-specific serum peptide signatures.
AB  - "Molecular signatures" are the qualitative and quantitative patterns of groups of
      biomolecules (e.g., mRNA, proteins, peptides, or metabolites) in a cell, tissue,
      biological fluid, or an entire organism. To apply this concept to biomarker
      discovery, the measurements should ideally be noninvasive and performed in a
      single read-out. We have therefore developed a peptidomics platform that couples
      magnetics-based, automated solid-phase extraction of small peptides with a high
      resolution MALDI-TOF mass spectrometric readout (Villanueva, J.; Philip, J.;
      Entenberg, D.; Chaparro, C. A.; Tanwar, M. K.; Holland, E. C.; Tempst, P. Anal.
      Chem. 2004, 76, 1560-1570). Since hundreds of peptides can be detected in
      microliter volumes of serum, it allows to search for disease signatures, for
      instance in the presence of cancer. We have now evaluated, optimized, and
      standardized a number of clinical and analytical chemistry variables that are
      major sources of bias; ranging from blood collection and clotting, to serum
      storage and handling, automated peptide extraction, crystallization, spectral
      acquisition, and signal processing. In addition, proper alignment of spectra and
      user-friendly visualization tools are essential for meaningful, certifiable data
      mining. We introduce a minimal entropy algorithm, "Entropycal", that simplifies
      alignment and subsequent statistical analysis and increases the percentage of the
      highly distinguishing spectral information being retained after feature selection
      of the datasets. Using the improved analytical platform and tools, and a
      commercial statistics program, we found that sera from thyroid cancer patients
      can be distinguished from healthy controls based on an array of 98 discriminant
      peptides. With adequate technological and computational methods in place, and
      using rigorously standardized conditions, potential sources of patient related
      bias (e.g., gender, age, genetics, environmental, dietary, and other factors) may
      now be addressed.

PMID- 16083256
TI  - Utilizing human blood plasma for proteomic biomarker discovery.
AB  - Candidate proteomic biomarker discovery from human plasma holds both incredible
      clinical potential as well as significant challenges. The dynamic range of
      proteins within plasma is known to exceed 10(10), and many potential biomarkers
      are likely present at lower protein abundances. At present, proteomic based MS
      analyses provide a dynamic range typically not exceeding approximately 10(3) in a
      single spectrum, and approximately 10(4)-10(6) when combined with on-line
      separations (e.g., reversed-phase gradient liquid chromatography), and thus are
      generally insufficient for low level biomarker detection directly from human
      plasma. This limitation is providing an impetus for the development of
      experimental methodologies and strategies to increase the possible number of
      detections within this biofluid. Discussed is the diversity of available
      approaches currently used by our laboratory and others to utilize human plasma as
      a viable medium for biomarker discovery. Various separation, depletion,
      enrichment, and quantitative efforts as well as recent improvements in MS
      capabilities have resulted in measurable improvements in the detection and
      identification of lower abundance proteins (by approximately 10-10(2)). Despite
      these improvements, further advances are needed to provide a basis for discovery
      of candidate biomarkers at very low levels. Continued development of depletion
      and enrichment techniques, coupled with improved pre-MS separations (both at the
      protein and peptide level) holds promise in extending the dynamic range of
      proteomic analysis.

PMID- 16083257
TI  - Proteomics: from basic research to diagnostic application. A review of
      requirements & needs.
AB  - For several years proteomics research has been expected to lead to the finding of
      new markers that will translate into clinical tests applicable to samples such as
      serum, plasma and urine: so-called in vitro diagnostics (IVDs). Attempts to
      implement technologies applied in proteomics, in particular protein arrays and
      surface-enhanced laser desorption ionization time-of-flight mass spectrometry
      (SELDI-TOF MS), as IVD instruments have initiated constructive discussions on
      opportunities and challenges inherent in such a translation process also with
      respect to the use of multi-marker profiling approaches and pattern signatures in
      IVD. Taking into account the role that IVD plays in health care, we describe IVD
      requirements and needs. Subject to stringent costs versus benefit analyses, IVD
      has to provide reliable information about a person's condition, prognosis or risk
      to suffer a disease, thus supporting decisions on treatment or prevention. It is
      mandatory to fulfill requirements in routine IVD, including disease prevention,
      diagnosis, prognosis, and treatment monitoring or follow up among others. To
      fulfill IVD requirements, it is essential to (1) provide diagnostic tests that
      allow for definite and reliable diagnosis tied to a decision on interventions
      (prevention, treatment, or nontreatment), (2) meet stringent performance
      characteristics for each analyte (in particular test accuracy, including both
      precision of the measurement and trueness of the measurement), and (3) provide
      adequate diagnostic accuracy, i.e., diagnostic sensitivity and diagnostic
      specificity, determined by the desired positive and negative predictive values
      which depend on disease frequency. The fulfillment of essential IVD requirements
      is mandatory in the regulated environment of modern diagnostics. Addressing IVD
      needs at an early stage can support a timely and effective transition of findings
      and developments into routine diagnosis. IVD needs reflect features that are
      useful in clinical practice. This helps to generate acceptance and assists the
      implementation process. On the basis of IVD requirements and needs, we outline
      potential implications for clinical proteomics focused on applied research
      activities.

PMID- 16083258
TI  - Proteomics in the forefront of cancer biomarker discovery.

PMID- 16083259
TI  - Perspective: a program to improve protein biomarker discovery for cancer.
AB  - Biomarkers for cancer risk, early detection, prognosis, and therapeutic response
      promise to revolutionize cancer management. Protein biomarkers offer tremendous
      potential in this regard due to their great diversity and intimate involvement in
      physiology. An effective program to discover protein biomarkers using existing
      technology will require team science, an integrated informatics platform,
      identification and quantitation of candidate biomarkers in disease tissue, mouse
      models of disease, standardized reagents for analyzing candidate biomarkers in
      bodily fluids, and implementation of automation. Technology improvements for
      better fractionation of the proteome, selection of specific biomarkers from
      complex mixtures, and multiplexed assay of biomarkers would greatly enhance
      progress.

PMID- 16083260
TI  - Introduction to the Food and Drug Administration (FDA) regulatory process.
AB  - FDA oversight of medical devices, including in vitro diagnostic devices (IVDs or
      laboratory tests), in the United States was a direct result of the passage of the
      Medical Device Amendments of 1976. This law introduced a series of general
      controls for medical devices including registration and listing, requirements for
      production using good manufacturing practices, and requirements for post-market
      reporting of device failures. This produced for the first time a menu of
      laboratory tests on the market, a system to ensure these were produced
      consistently over time, and a mechanism for FDA to identify problems with device
      use and to work with companies to ensure corrective action. This law also
      introduced the requirement for premarket review of new versions of old devices
      and of fundamentally new medical devices.

PMID- 16083261
TI  - Building integrated approaches for the proteomics of complex, dynamic systems:
      NIH programs in technology and infrastructure development.
AB  - Proteomics technology and methods remain inadequate. Technological constraints
      contribute to an artificially static view of complex biological systems and a
      barrier between quantitative and interaction studies. Several NIH programs
      combine proteomics technology development with research on challenging biological
      problems to drive progress. A new initiative of the NIH Roadmap focuses on
      characterization of dynamic systems. The success of these programs will be judged
      by their impact on relevant biological problems.

PMID- 16083263
TI  - Imaging biomarkers in drug development: an overview of opportunities and open
      issues.

PMID- 16083262
TI  - The sentinel within: exploiting the immune system for cancer biomarkers.
AB  - The release of proteins from tumors triggers an immune response in cancer
      patients. These tumor antigens arise from several mechanisms including tumor
      specific alterations in protein expression, mutation, folding, degradation, or
      intracellular localization. Responses to most tumor antigens are rarely observed
      in healthy individuals, making the response itself a biomarker that betrays the
      presence of underlying cancer. Antibody immune responses show promise as clinical
      biomarkers because antibodies have long half-lives in serum, are easy to measure,
      and are stable in blood samples. However, our understanding of the specificity
      and the impact of the immune response in early stages of cancer is limited. The
      immune response to cancer, whether endogenous or driven by vaccines, involves
      highly specific T lymphocytes (which target tumor-derived peptides bound to self
      MHC proteins) and B lymphocytes (which generate antibodies to tumor-derived
      proteins). T cell target antigens have been identified either by expression
      cloning from tumor cDNA libraries, or by prediction based on patterns of antigen
      expression ("reverse immunology"). B cell targets have been similarly identified
      using the antibodies in patient sera to screen cDNA libraries derived from tumor
      cell lines. This review focuses on the application of recent advances in
      proteomics for the identification of tumor antigens. These advances are opening
      the door for targeted vaccine development, and for using immune response
      signatures as biomarkers for cancer diagnosis and monitoring.

PMID- 16083264
TI  - MALDI mass spectrometry for direct tissue analysis: a new tool for biomarker
      discovery.
AB  - The direct analysis of tissue sections by MALDI mass spectrometry holds
      tremendous potential for biomarker discovery. This technology routinely allows
      many hundreds of proteins to be detected over a mass range of approximately 2000
      70 000 Da while maintaining the spatial localization of the proteins detected.
      This technology has been applied to a wide range of tissue samples, including
      human glioma tissue and human lung tumor tissue. In many cases, biostatistical
      analyses of the resulting protein profiles revealed patterns that correlated with
      disease state and/or clinical endpoints. This work serves as a review of recent
      applications and summarizes the current state of technology.

PMID- 16083265
TI  - Place of pattern in proteomic biomarker discovery.
AB  - The role of pattern in biomarker discovery and clinical diagnosis is examined in
      its historical context. The use of MS-derived pattern is treated as a logical
      extension of prior applications of non-MS-derived pattern. Criticisms pertaining
      to specific technology platforms and analytic methodologies are considered
      separately from the larger issues of pattern utility and deployment in biomarker
      discovery. We present a hybrid strategy that marries the desirable attributes of
      high-information content MS pattern with the capability to obtain identity, and
      explore the key steps in establishing a data analysis pipeline for pattern-based
      biomarker discovery.

PMID- 16083266
TI  - Extended Range Proteomic Analysis (ERPA): a new and sensitive LC-MS platform for
      high sequence coverage of complex proteins with extensive post-translational
      modifications-comprehensive analysis of beta-casein and epidermal growth factor
      receptor (EGFR).
AB  - We have developed a new and sensitive LC-MS platform, Extended Range Proteomic
      Analysis (ERPA), which is able to achieve very high sequence coverage and
      comprehensive characterization of post-translational modifications in complex
      proteins. This new platform provides advantages of both the top-down and bottom
      up proteomic approaches by combining (i) digestion of the protein with an enzyme,
      such as Lys-C, which cuts less frequently than trypsin, leading to on average a
      higher molecular weight peptide size, (ii) high-performance LC separation of the
      resulting fragments, (iii) a new data acquisition strategy using the LTQ-FTMS, a
      hybrid mass spectrometer that couples a linear ion trap with a Fourier transform
      ion cyclotron resonance (FTICR) cell, for analysis of peptides in the range of
      0.5 to 10 kDa, and (iv) new data analysis methods for assigning large peptide
      structures and determining the site of attachment of post-translational
      modifications as well as structural features from the accurate precursor mass
      together with MS(2) and MS(3) fragmentations. The LC retention of the Lys-C
      fragments is increased, relative to a tryptic digest, due to the generally
      greater hydrophobicity of the larger peptides, a result that is particularly
      important for peptides containing hydrophilic modifications such as glycosylation
      and phosphorylation. Furthermore, additional positively charged arginine and
      lysine residues in the Lys-C fragments enhance the sensitivity of the post
      translationally modified phospho- and glycopeptides by at least 10-fold relative
      to tryptic fragments. In typical operation, the FTICR cell provides a survey scan
      with the high mass resolution (> 100 000) and accurate mass (<2 ppm) to
      characterize the higher charge-state precursor ions of the larger peptides. In
      parallel, the linear ion trap provides MS(2) and MS(3) fragmentation spectra,
      with a scan speed sufficiently fast for on-line LC-MS. Together, these data
      provide multiple means to determine or enhance the confidence of assignment of
      large or complicated peptide. Using ERPA, we demonstrate >95% sequence coverage
      in the analysis of two heavily phosphorylated and glycosylated proteins, beta
      casein at the 50 fmole level and the epidermal growth factor receptor (EGFR) at
      the 1 pmole level. In summary, the combination of digestion strategy, high
      performance separation, and the hybrid LTQ-FTMS instrument enables comprehensive
      characterization of large proteins, including posttranslational modifications.

PMID- 16083267
TI  - Proteomic maps of the cancer-associated infectious agents.
AB  - The number of infectious agents associated with cancer is increasing. There is a
      need to develop approaches for the early detection of the infected host which
      might lead to tumor development. Recent advances in proteomic approaches provide
      that opportunity, and it is now possible to generate proteomic maps of cancer
      associated infectious agents. Protein arrays, interaction maps, data archives,
      and biological assays are being developed to enable efficient and reliable
      protein identification and functional analysis. Herein, we discuss the current
      technologies and challenges in the field, and application of protein signatures
      in cancer detection and prevention.

PMID- 16083268
TI  - Quest for novel cardiovascular biomarkers by proteomic analysis.
AB  - Atherosclerosis, and the resulting coronary heart disease and stroke, is the most
      common cause of death in developed countries. Atherosclerosis is an inflammatory
      process that results in the development of complex lesions or plaques that
      protrude into the arterial lumen. Plaque rupture and thrombosis result in the
      acute clinical complications of myocardial infarction (MI) and stroke. Although
      certain risk factors (dyslipidemias, diabetes, hypertension) and humoral markers
      of plaque vulnerability (C-reactive protein, interleukin-6, 10 and 18, CD40L)
      have been identified, a highly sensitive and specific biomarker or protein
      profile, which could provide information on the stability/vulnerability of
      atherosclerotic lesions, remains to be identified. In this review, we report
      several proteomic approaches which have been applied to circulating or resident
      cells, atherosclerotic plaques or plasma, in the search for new proteins that
      could be used as cardiovascular biomarkers. First, an example using a
      differential proteomic approach (2-DE and MS) comparing the secretome from
      control mammary arteries and atherosclerotic plaques is displayed. Among the
      different proteins identified, we showed that low levels of HSP-27 could be a
      potential marker of atherosclerosis. Second, we have revised several studies
      performed in cells involved in the pathogenesis of atherosclerosis (foam cells
      and smooth muscle cells). Another approach consists of performing proteomic
      analysis on circulating cells or plasma, which will provide a global view of the
      whole body response to atherosclerotic aggression. Circulating cells can bear
      information reflecting directly an inflammatory or pro-coagulant state related to
      the pathology. As an illustration, we report that circulating monocytes and
      plasma in patients with acute coronary syndromes has disclosed that mature
      Cathepsin D is increased both in the plasma and monocytes of these patients.
      Finally, the problems of applying proteomic approach directly to plasma will be
      discussed. The purpose of this review is to provide the reader with an overview
      of different proteomic approaches that can be used to identify new biomarkers in
      vascular diseases.

PMID- 16083269
TI  - Evaluation of biomarker discovery approaches to detect protein biomarkers of
      acute renal allograft rejection.
AB  - Management of host responses to allografts by immunosuppressive therapy is the
      cornerstone of transplantation medicine, but it is still deficient in one
      important element: biomarkers that are readily accessible and predict the fate of
      the transplant early, specifically, and reliably. Using a Brown Norway (BN)-to
      Lewis rat renal allograft model of kidney transplantation, this study aims at
      evaluating two proteomic approaches to discover biomarkers for acute rejection:
      SELDI-MS technology and 2D gel electrophoresis combined with mass spectrometry.
      Several novel potential serum biomarkers have been identified for follow up.
      Overall, the conclusion is that apparently at the serum protein level, dramatic
      changes only occur at a stage where kidney function is already severely affected.
      Multivariate analysis of serum profiles suggests that there is an ensemble of
      subtle changes, comprising a proteomic signature of acute rejection at an early
      stage, a more detailed evaluation of which might provide novel opportunities for
      the diagnosis of acute rejection. Profiling of the excreted proteins indicates
      that urine might even present the earliest signs of the rejection process.

PMID- 16083270
TI  - Discovery of biomarker candidates within disease by protein profiling: principles
      and concepts.
AB  - Proteins and peptides present within clinical samples represent a valuable
      library of information regarding the ongoing processes within cells and tissues
      in health and disease. We have developed and validated novel technology
      applications that can be used to characterize the patterns of global protein
      expression in tissue and biofluids in either gel-based systems or by automated
      multidimensional nanocapillary liquid chromatography. Mass spectrophotometry
      platforms using MALDI MS and MS/MS or LTQ ion trap MS were capable of delivering
      sensitive and accurate identifications of hundreds of proteins contained in
      individual samples including individual forms of processing intermediates such as
      phospho peptides. The Systems Biology approach of integrating protein expression
      data with clinical data such as histopathology, clinical functional measurements,
      medical imaging scores, patient demographics, and clinical outcome provides a
      powerful tool for linking biomarker expression with biological processes that can
      be segmented and linked to disease presentation.

PMID- 16083271
TI  - Clinical cancer proteomics: promises and pitfalls.
AB  - Proteome analysis promises to be valuable for the identification of tissue and
      serum biomarkers associated with human malignancies. In addition, proteome
      technologies offer the opportunity to analyze protein expression profiles and to
      analyze the activity of signaling pathways. Many published proteomic studies of
      human tumor tissue are associated with weaknesses in tumor representativity,
      sample contamination by nontumor cells and serum proteins. Studies often include
      a moderate number of tumors which may not be representative of clinical
      materials. It is therefore very important that biomarkers identified by
      proteomics are validated in representative tumor materials by other techniques,
      such as immunohistochemistry. Proteome technologies can be used to identify
      disease markers in human serum. Tumor derived proteins are present at nanomolar
      to picomolar concentrations in cancer patient sera, 10(6)-10(9)-fold lower than
      albumin, and will give rise to correspondingly smaller spots/peaks in protein
      separations. This leads to the need to prefractionate serum samples before
      analysis. Despite various pitfalls, proteomic analysis is a promising approach to
      the identification of biomarkers, and for generation of protein expression
      profiles that can be analyzed by artificial learning methods for improved
      diagnosis of human malignancy. Recent advances in the field of proteomic analysis
      of human tumors are summarized in the present review.

PMID- 16083272
TI  - Mapping the proteome of Drosophila melanogaster: analysis of embryos and adult
      heads by LC-IMS-MS methods.
AB  - Multidimensional separations combined with mass spectrometry are used to study
      the proteins that are present in two states of Drosophila melanogaster: the whole
      embryo and the adult head. The approach includes the incorporation of a gas-phase
      separation dimension in which ions are dispersed according to differences in
      their mobilities and is described as a means of providing a detailed analytical
      map of the proteins that are present. Overall, we find evidence for 1133 unique
      proteins. In total, 780 are identified in the head, and 660 are identified in the
      embryo. Only 307 proteins are in common to both developmental stages, indicating
      that there are significant differences in these proteomes. A comparison of the
      proteome to a database of mRNAs that are found from analysis by cDNA approaches
      (i.e., transcriptome) also shows little overlap. All of this information is
      discussed in terms of the relationship between the predicted genome, and measured
      transcriptomes and proteomes. Additionally, the merits and weaknesses of current
      technologies are assessed in some detail.

PMID- 16083273
TI  - Proteome profiling for assessing diversity: analysis of individual heads of
      Drosophila melanogaster using LC-ion mobility-MS.
AB  - The proteomes of three heads of individual Drosophila melanogaster organisms have
      been analyzed and compared by a combination of liquid chromatography, ion
      mobility spectrometry, and mass spectrometry approaches. In total, 197 proteins
      are identified among all three individuals (an average of 120 +/- 20 proteins per
      individual), of which at least 101 proteins are present in all three individuals.
      Within all three datasets, more than 25 000 molecular ions (an average of 9000 +/
      2000 per individual) corresponding to protonated precursor ions of individual
      peptides have been observed. A comparison of peaks among the datasets reveals
      that peaks corresponding to protonated peptides that are found in all heads are
      more intense than those features that appear between pairs of or within only one
      of the individuals. Moreover, there is little variability in the relative
      intensities of the peaks common among all individuals. It appears that it is the
      lower abundance components of the proteome that play the most significant role in
      determining unique features of individuals.

PMID- 16083274
TI  - Plasma protein level changes in waste incineration workers exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a chemical compound which is known
      to induce severe reproductive and developmental problems, immune system damage,
      and interference with regulatory hormones. To characterize changes in the
      expression of plasma proteins caused by exposure to TCDD, we analyzed plasma
      samples from workers at municipal incinerators using two-dimensional gel
      electrophoresis (2-DE). Proteins exhibiting differences in expression were
      identified by matrix-assisted laser desorption ionization time-of-flight (MALDI
      TOF) and electrospray ionization quadrupole (ESI-Q) TOF mass spectrometry. One
      newly expressed protein was identified as the adrenomedulin binding protein
      (AMBP). Seven overexpressed proteins were identified in this study, and the most
      overexpressed protein was identified as alpha-fetoprotein (AFP). In addition, we
      cultured HepG2 cells in the presence of TCDD, to determine the effects of TCDD on
      the AFP and albumin expression in mRNA and protein levels, via RT-PCR and Western
      blotting, respectively. TCDD treatment resulted in an increase in the mRNA and
      protein expression levels of AFP, but reduced albumin expression. According to
      our results, exposure to TCDD may induce liver disease or cancer, and the
      proteins identified in this study could help reveal the mechanisms underlying
      TCDD toxicity.

PMID- 16083275
TI  - Prefractionation of proteome by liquid isoelectric focusing prior to two
      dimensional liquid chromatography mass spectrometric identification.
AB  - Due to the complexity of proteomes, developing methods of sample fractionation,
      separation, concentration, and detection have become urgent to the identification
      of large numbers of proteins, as well as the acquisition of those proteins in low
      abundance. In this work, liquid isoelectric focusing (LIEF) combined with 2D-LC
      MS/MS was applied to the proteome of Saccharomyces cerevisiae. This yielded a
      total of 1795 proteins that were detected and identified by 30 fractions of
      protein prefractionation. Categorization of these hits demonstrated the ability
      of this technology to detect and identify proteins rarely seen in proteome
      analysis without protein fractionation. LIEF-2D-LC-MS/MS also produced improved
      resolution of low-abundance proteins. Furthermore, we analyzed the
      characteristics of proteins obtained by LIEF-2D-LC-MS/MS. 1103 proteins with CAI
      under 0.2 were identified, allowing us to specifically obtain detailed
      biochemical information on these kind proteins. It was observed that LIEF-2D-LC
      MS/MS is useful for large-scale proteome analysis and may be specifically applied
      to systems with wide dynamic ranges.

PMID- 16083276
TI  - High-sensitivity analysis of human plasma proteome by immobilized isoelectric
      focusing fractionation coupled to mass spectrometry identification.
AB  - Immobilized pH gradients isoelectric focusing (IPG-IEF) is the first dimension
      typically used in two-dimensional gel electrophoresis (2-DE). It can also be used
      on its own in conjunction with tandem mass spectrometry (MS/MS) for the analysis
      of proteins. Here, we described a strategy combining isoelectric focusing in
      immobilized pH gradient strips, and mass spectrometry to create a new high
      throughput and sensitive detection method. Protein mixture is separated by in-gel
      IEF, then the entire strip is cut into a set of gel sections. Proteins in each
      gel section are digested with trypsin, and the resulted peptides are subjected to
      reversed-phase high performance liquid chromatography followed by electrospray
      linear ion-trap tandem mass analysis. Using this optimized strategy, we have
      identified 744 distinct human proteins from an IPG strip loaded only 300 microg
      of plasma proteins. When compared with other works in published literatures, this
      study offered a more convenient and sensitive method from gel to mass
      spectrometry for the separation and identification proteins of complex biological
      samples.

PMID- 16083277
TI  - Proteomic profiling of human pleural effusion using two-dimensional nano liquid
      chromatography tandem mass spectrometry.
AB  - Pleural effusion, an accumulation of pleural fluid, contains proteins originated
      from plasma filtrate and, especially when tissues are damaged, parenchyma
      interstitial spaces of lungs and/or other organs. This study details protein
      profiles in human pleural effusion from 43 lung adenocarcinoma patients by a two
      dimensional nano-high performance liquid chromatography electrospray ionization
      tandem mass spectrometry (2D nano-HPLC-ESI-MS/MS) system. The experimental
      results revealed the identification of 1415 unique proteins from human pleural
      effusion. Among these 124 proteins identified with higher confidence levels, some
      proteins have not been reported in plasma and may represent proteins specifically
      present in pleural effusion. These proteins are valuable for mass identification
      of differentially expressed proteins involved in proteomics database and
      screening biomarker to further study in human lung adenocarcinoma. The
      significance of the use of proteomics analysis of human pleural fluid for the
      search of new lung cancer marker proteins, and for their simultaneous display and
      analysis in patients suffering from lung disorders has been examined.

PMID- 16083278
TI  - Peptide sequence tags for fast database search in mass-spectrometry.
AB  - Filtration techniques in the form of rapid elimination of candidate sequences
      while retaining the true one are key ingredients of database searches in
      genomics. Although SEQUEST and Mascot perform a conceptually similar task to the
      tool BLAST, the key algorithmic idea of BLAST (filtration) was never implemented
      in these tools. As a result MS/MS protein identification tools are becoming too
      time-consuming for many applications including search for post-translationally
      modified peptides. Moreover, matching millions of spectra against all known
      proteins will soon make these tools too slow in the same way that "genome vs
      genome" comparisons instantly made BLAST too slow. We describe the development of
      filters for MS/MS database searches that dramatically reduce the running time and
      effectively remove the bottlenecks in searching the huge space of protein
      modifications. Our approach, based on a probability model for determining the
      accuracy of sequence tags, achieves superior results compared to GutenTag, a
      popular tag generation algorithm. Our tag generating algorithm along with our de
      novo sequencing algorithm PepNovo can be accessed via the URL
      http://peptide.ucsd.edu/.

PMID- 16083279
TI  - Searching for biomarkers of Aurora-A kinase activity: identification of in vitro
      substrates through a modified KESTREL approach.
AB  - Aurora-A, -B, and -C are members of a small family of mitotic serine/threonine
      kinases that regulate centrosome maturation, chromosome segregation, and
      cytokinesis. They are often overexpressed in different human tumor types and have
      been identified as attractive targets for anticancer drug development. As
      specific inhibitors of the Aurora kinases are entering phase I clinical trials,
      there is a high need for appropriate Aurora-A biomarkers to follow mechanism of
      action or response. To identify novel Aurora-A substrates potentially useful as
      specific biomarkers we applied several modifications to the original KESTREL
      (Kinase Substrate Tracking and Elucidation) method in conjunction with gel
      electrophoresis and MALDI-MS and LC-MS/MS. The major modifications to the method
      included the introduction of a heating step to inactivate endogenous kinases
      after cell lysis and the execution of the in vitro kinase reaction in the
      presence of 5 mM Mg(2+) and at high (1 mM) ATP concentration. Total and
      fractionated extracts from nocodazole-treated HeLa cells were used as a source of
      Aurora-A substrates. Using this approach, we were able to detect a number of
      Aurora-A specific phospholabeled signals and to identify vimentin as a putative
      Aurora-A substrate. Vimentin was then confirmed as an in vitro substrate of
      Aurora-A by the phosphorylation of the recombinant protein followed by MS and
      antibody detection.

PMID- 16083280
TI  - Proteomic analysis of erythrocyte membranes by soft Immobiline gels combined with
      differential protein extraction.
AB  - Improvements in proteome analysis of erythrocyte membrane proteins by two
      dimensional electrophoresis are here reported. In particular, a differential
      extraction procedure was set up allowing separation of integral membrane proteins
      from peripheral species. Moreover, the use of dilute Immobiline gels (down to as
      low as 3% T matrix) permitted a better penetration and transfer inside the gel of
      proteins with large M(r). These protocol modifications, combined with sample
      delipidation and alkylation prior to electrophoresis, which prevented generation
      of homo- and hetero-oligomers following disulfide scrambling phenomena, allowed
      the display of more than 500 spots in the pI/M(r) plane. Among those, noteworthy
      was the presence of high levels of filamentous proteins, such as alpha-spectrin
      and ankyrins, or integral membrane proteins, such as band 3, band 4.1 and 4.2,
      not displayed or barely present in other maps exploiting immobilized pH gradients
      in the first dimension. Accordingly, our results show that this 2D mapping
      technique is a valuable tool in exploring pathologies related to genetic defects
      associated to membrane proteins.

PMID- 16083281
TI  - Quantitative protein expression analysis of CLL B cells from mutated and
      unmutated IgV(H) subgroups using acid-cleavable isotope-coded affinity tag
      reagents.
AB  - Relative protein expression levels were compared in leukemic B cells from two
      patients with chronic lymphocytic leukemia (CLL) having either mutated (M-CLL) or
      unmutated (UM-CLL) immunoglobulin variable heavy chain genes (IgV(H)). Cells were
      separated into cytosol and membrane protein fractions then labeled with acid
      cleavable ICAT reagents (cICAT). Labeled proteins were digested with trypsin then
      subjected to SCX and affinity chromatography followed by LC-ESI-MS/MS analysis on
      a linear ion trap mass spectrometer. A total of 9 proteins from the cytosol
      fraction and 4 from the membrane fraction showed a 3-fold or greater difference
      between M-CLL and UM-CLL and a subset of these were examined by Western blot
      where results concurred with cICAT abundance ratios. The abundance of one of the
      proteins in particular, the mitochondrial membrane protein cytochrome c oxidase
      subunit COX G was examined in 6 M-CLL and 6 UM-CLL patients using western blot
      and results showed significantly greater levels (P < 0.001) in M-CLL patients vs
      UM-CLL patients. These results demonstrate that stable isotope labeling and mass
      spectrometry can complement 2D gel electrophoresis and gene microarray
      technologies for identifying putative and perhaps unique prognostic markers in
      CLL.

PMID- 16083282
TI  - Application of relative warp analysis to the evaluation of two-dimensional gels
      in proteomics: studying isoelectric point and relative molecular mass variation.
AB  - We propose a geometric-morphometrics method (relative warp analysis) to be used
      in proteomic comparisons. This approach was applied to a dataset from a
      comparison between 5 controls and 5 patients with colorectal cancer disease
      published elsewhere. The spots in the 2-D maps were used as landmarks in a
      morphometric study, and the differences in shape (spot distribution) among them
      were obtained. The shape variables were used to compare controls and patients.
      These components mostly ignore random or experimental effects affecting all the
      proteins in any of the two dimensions studied. Furthermore, the method allows the
      researcher to find those proteins which contributed the most to the local shape
      component detected. Applying this approach, we detected variations in the
      position (isoelectric point and/or relative molecular mass) of some spots that
      may reflect differences in the amino acidic sequence or post-translational
      modifications.

PMID- 16083283
TI  - Biochemical characterization of rat intestine development using high-resolution
      magic-angle-spinning 1H NMR spectroscopy and multivariate data analysis.
AB  - We report details of metabolic profiles for small intestinal samples obtained
      using high-resolution magic-angle-spinning (HRMAS) (1)H NMR spectroscopy. Intact
      samples of jejunum and ileum from male Long Evans rats were analyzed on a 600 MHz
      spectrometer using standard one and two-dimensional (1)H NMR spectroscopic pulse
      sequences. The metabolic profiles of ileum and jejunum predominantly comprised a
      number of amino acids, lipids, glycerophosphocholine (GPC), choline, creatine,
      and ethanol, a number of carboxylic acids including acetate and lactate, and
      nucleoside bases including cytosine, isocytosine, and uracil. Principal component
      analysis (PCA) was applied to these NMR data to characterize the biochemical
      differences between jejunum and ileum tissues. Compared with ileum, jejunum
      contained higher levels of lipids, GPC, choline, lactate and creatinine, but
      lower levels of amino acids and acetate. In addition, the age dependence of the
      biochemical composition of intestinal tissues from young rats (15, 36 days and 3
      4 months old) was studied. In general, levels of lipids, lactate, taurine and
      creatinine were positively correlated with age while amino acids and GPC
      decreased in the older age group. This study will provide a metabolic reference
      for further studies assessing the metabolic consequences of nutrition, stress and
      gut microbiota on intestinal composition.

PMID- 16083284
TI  - Proteomic analysis of the outer membrane of Anabaena sp. strain PCC 7120.
AB  - Anabaena is a model to analyze the evolutionary development of plastids, cell
      differentiation, and the regulation of nitrogen fixation. Thereby, the outer
      membrane proteome is the place of sensing environmental differences and during
      plastid development, systems for intracellular communication had to be added to
      the proteome of this membrane. We present a protocol for the isolation of the
      outer membrane from Anabaena and the analysis of the proteome using different
      tools. 55 proteins were identified.

PMID- 16083285
TI  - Global phosphoproteome of HT-29 human colon adenocarcinoma cells.
AB  - Phosphorylation events in cellular signaling cascades triggered by a variety of
      cellular stimuli modulate protein function, leading to diverse cellular outcomes
      including cell division, growth, death, and differentiation. Abnormal regulation
      of protein phosphorylation due to mutation or overexpression of signaling
      proteins often results in various disease states. We provide here a list of
      protein phosphorylation sites identified from HT-29 human colon adenocarcinoma
      cell line by immobilized metal affinity chromatography (IMAC) combined with
      liquid chromatography (LC)-tandem mass spectrometry (MS/MS) analysis. In this
      study, proteins extracted from HT-29 whole cell lysates were digested with
      trypsin and carboxylate groups on the resulting peptides were converted to methyl
      esters. Derivatized phosphorylated peptides were enriched using Fe(3+)-chelated
      metal affinity resin. Phosphopeptides retained by IMAC were separated by high
      performance liquid chromatography (HPLC) and analyzed by electrospray ionization
      quadrupole-time-of-flight (ESI-Q-TOF) mass spectrometry. We identified 238
      phosphorylation sites, 213 of which could be conclusively localized to a single
      residue, from 116 proteins by searching MS/MS spectra against the human protein
      database using MASCOT. Peptide identification and phosphorylation site assignment
      were confirmed by manual inspection of the MS/MS spectra. Many of the
      phosphorylation sites identified in our results have not been described
      previously in the scientific literature. We attempted to ascribe functionality to
      the sites identified in this work by searching for potential kinase motifs with
      Scansite (http://scansite.mit.edu) and obtaining information on kinase substrate
      selectivity from Pattern Explorer (http://scansite.mit.edu/pe). The list of
      protein phosphorylation sites identified in the present experiment provides broad
      information on phosphorylated proteins under normal (asynchronous) cell culture
      conditions. Sites identified in this study may be utilized as surrogate bio
      markers to assess the activity of selected kinases and signaling pathways from
      different cell states and exogenous stimuli.

PMID- 16083286
TI  - Canonical labeling of proteome maps.
AB  - We propose a canonical labeling of proteome maps, which enables one to sort and
      catalog the maps in a simple way. The canonical label of a proteome map is based
      on the canonical labeling of vertexes of Hasse diagram embedded in the map
      resulting in the adjacency matrix, the rows of which when viewed as binary
      numbers are the smallest possible such numbers. The use of the approach in
      documentation is illustrated with the proteome maps of liver cells of healthy
      male Fisher F344 rats and the rats treated with different peroxisome
      proliferators.

PMID- 16083287
TI  - Large scale analysis of MASCOT results using a Mass Accuracy-based THreshold
      (MATH) effectively improves data interpretation.
AB  - In this report, we take a heuristic approach to studying the effects of mass
      tolerance settings and database size on the sensitivity and specificity of
      MASCOT. We also examine the efficacy of the MASCOT Identity Threshold as a
      discriminator when applied to QqTOF data with an average mass accuracy of 10 ppm
      or better. As predicted, arbitrarily large mass tolerance settings negatively
      affect MASCOT's specificity, and to a lesser degree, sensitivity. Increased mass
      tolerances also render the generation of a significance threshold less effective.
      To study these effects, we used Bayes' Law to calculate MASCOT's predictive
      values. With a relatively small search database (Human IPI), MASCOT had a mean
      positive predictive value of 0.993 when combined with MASCOT's Identity
      Threshold. However, the corresponding average negative predictive value, or the
      probability that an ion was not present given no score or a score below
      threshold, was reduced as mass tolerances were tightened, and had an average
      value of 0.717. This value was improved upon by extrapolating an empirical
      threshold using a reversed database search and a new algorithm to rapidly
      identify false positive identifications. Using the empirical threshold reduced
      false negative identifications on the average 17% while limiting the false
      positive rate to below 5%; even larger reductions were obtained using mass
      tolerances approaching two times the actual error of the experimental data. A
      simple application of this strategy to the analysis of a microdissected
      glioblastoma multiforme sample analyzed by IEF/LC-MS/MS is reported, as is a
      description of the tools required to implement a large scale analysis using this
      alternative approach.

PMID- 16083288
TI  - Inventory of the proteins in Neisseria meningitidis serogroup B strain MC58.
AB  - A protein inventory of Neisseria meningitidis strain MC58, a meningococcal strain
      belonging to the serogroup B, was performed by proteomics. A differential
      extraction procedure was employed and 238 protein species were identified by 2D
      mini-maps and MALDI-ToF analyses. In this catalog, we detected protein products
      from 33 genes, which were not yet annotated in previous N. meningitidis proteomic
      studies. This approach is suitable for high-throughput studies on differential
      expression of N. meningitidis genomes.

PMID- 16083289
TI  - Application of two-dimensional difference gel electrophoresis to studying bone
      marrow macrophages and their in vivo responses to ionizing radiation.
AB  - A flow cytometric protocol was developed to isolate primary bone marrow resident
      macrophages (CD11b((-)) Gr-1((-)) F4/80((+))) before and 24 h after 0.5 Gy gamma
      irradiation from mouse strains (C57BL/6 and CBA/Ca) that exhibit significant
      differences in the response of their hematopoietic tissues to ionizing radiation.
      The proteins from these populations were analyzed using two-dimensional
      difference gel electrophoresis (2D DIGE) and mass spectrometry. We identified 36
      macrophage proteins from 52 spots in both C57BL/6 and CBA/Ca. Thirty-three spots
      showed significant difference between genotypes and 16 of them corresponding to
      11 proteins were identified. These included G-protein signaling 16, glucose
      regulated protein 78, and lactoylglutathione lyase. We detected 16 and 18 spot
      changes following irradiation in C57BL/6 and CBA/Ca respectively, and in total 16
      of them were identified. The identified proteins included calreticulin,
      lactoylglutathione lyase, regulator of G-protein signaling 16 and peroxiredoxin
      5, mitochondrial precursor. The application of DIGE to primary bone marrow
      resident macrophages has allowed the first description of the proteome of these
      important components of the hematopoietic microenvironment and an analysis of
      their in vivo response to ionizing radiation which may shed light on the
      mechanism underlying the differential radiation-induced leukemogenesis exhibited
      within these mouse strains.

PMID- 16083290
TI  - Identification of novel and cell type enriched cofactors of the transcription
      activation domain of RelA (p65 NF-kappaB).
AB  - RelA (NF-kappaB) is a transcription factor inducible by distinct stimuli in many
      different cell types. To find new cell type specific cofactors of NF-kappaB
      dependent transcription, we isolated RelA transcription activation domain binding
      proteins from the nuclear extracts of three different cell types. Analysis by
      electrophoresis and liquid chromatography tandem mass spectrometry identified
      several novel putative molecular partners. Some were strongly enriched in the
      complex formed from the nuclear extracts of specific cell types.

PMID- 16083291
TI  - Direct matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometric identification of proteins on membrane detected by Western blotting
      and lectin blotting.
AB  - We have developed new procedures to identify proteins after they are detected by
      Western blotting or other interactions such as lectin blotting on membranes. Our
      method is based on the combination of on-membrane MALDI-TOF mass spectrometry
      with piezoelectric chemical inkjet technology. Using this method the GroEL, FtsZ,
      DnaK, and GroES proteins were successfully identified from Escherichia coli after
      separation on two-dimensional gels, immunostaining, and on-membrane digestion. A
      glycoprotein detected by lectin blotting with concanavalin A was also identified
      using this technique.

PMID- 16083292
TI  - Amazing stability of the arginine-phosphate electrostatic interaction.
AB  - Electrostatic interactions between a basic epitope containing adjacent arginine
      residues and an acidic epitope containing a phosphorylated serine are involved in
      receptor heteromerization. In the present study, we demonstrate that this
      arginine-phosphate electrostatic interaction possesses a "covalent-like"
      stability. Hence, these bonds can withstand fragmentation by mass spectrometric
      collision-induced dissociation at energies similar to those that fragment
      covalent bonds and they demonstrate an extremely low dissociation constant by
      plasmon resonance. The present work also highlights the importance of
      phosphorylation-dephosphorylation events in the modulation of this electrostatic
      attraction. Phosphorylation of the acidic epitope, a casein kinase one consensus
      site, makes it available to interact with the basic epitope. On the other hand,
      phosphorylation of serine and/or threonine residues adjacent to the basic
      epitope, a protein kinase A consensus site, slows down the attraction between the
      epitopes. Although analyzed here in the frame of receptor heteromerization, the
      arginine-phosphate electrostatic interaction most likely represents a general
      mechanism in protein-protein interactions.

PMID- 16083293
TI  - Mass tagging approach for mitochondrial thiol proteins.
AB  - A mass tagging approach is described for mitochondrial thiol proteins under
      nondenaturing conditions. This approach utilizes stable isotope-coded, thiol
      reactive (4-iodobutyl)triphenylphosphonium (IBTP) reagents, i.e., the isotopomers
      IBTP-d(0) and IBTP-d(15). The mass spectrometric properties of IBTP-labeled
      peptides were evaluated using an ESI-q-TOF and a MALDI-TOF/TOF instrument. High
      energy collision induced dissociation (CID) in the TOF/TOF instrument caused side
      chain fragmentation in the butyltriphenylphosphonium moiety-containing Cys
      residue. By contrast, low energy CID in the qTOF instrument yielded sequence tags
      of IBTP-labeled peptides that were suitable for automated database searching. The
      IBTP labeling strategy was then applied to the analysis of a protein extract
      obtained from cardiac mitochondria. The relative abundance measurements for
      identified IBTP-labeled peptides showed an average variability for peptide
      quantitation of approximately 10% based on peak area ratios of ion signals for
      the d(0)/d(15)-tagged peptide pairs. The reactivity of the IBTP reagents was
      further studied by molecular modeling and visualization. The present study
      suggests that the IBTP reagent seems to show a bias toward highly surface-exposed
      protein thiols. Hence, the described mass tagging approach might become
      potentially useful in redox proteomics studies designed to identify protein
      thiols that are particularly prone to oxidative modifications.

PMID- 16083294
TI  - Prediction of G-protein-coupled receptor classes.
AB  - Being the largest family of cell surface receptors, G-protein-coupled receptors
      (GPCRs) are among the most frequent targets of therapeutic drugs. The functions
      of many of GPCRs are unknown, and it is both time-consuming and expensive to
      determine their ligands and signaling pathways. This forces us to face a critical
      challenge: how to develop an automated method for classifying the family of GPCRs
      so as to help us in classifying drugs and expedite the process of drug discovery.
      Owing to their highly divergent nature, it is difficult to predict the
      classification of GPCRs by means of conventional sequence alignment approaches.
      To cope with such a situation, the CD (Covariant Discriminant) predictor was
      introduced to predict the families of GPCRs. The overall success rate thus
      obtained by jack-knife test for 1238 GPCRs classified into three main families,
      i.e., class A-"rhodopsin like", class B-"secretin like", and class C
      "metabotrophic/glutamate/pheromone", was over 97%. The high success rate suggests
      that the CD predictor holds very high potential to become a useful tool for
      understanding the actions of drugs that target GPCRs and designing new
      medications with fewer side effects and greater efficacy.

PMID- 16083295
TI  - Identification and quantification of differentially expressed proteins in E
      cadherin deficient SCC9 cells and SCC9 transfectants expressing E-cadherin by
      dimethyl isotope labeling, LC-MALDI MS and MS/MS.
AB  - A strategy based on isotope labeling of peptides and liquid chromatography matrix
      assisted laser desorption ionization mass spectrometry (LC-MALDI MS) has been
      employed to accurately quantify and confidently identify differentially expressed
      proteins between an E-cadherin-deficient human carcinoma cell line (SCC9) and its
      transfectants expressing E-cadherin (SCC9-E). Proteins extracted from each cell
      line were tryptically digested and the resultant peptides were labeled
      individually with either d(0)- or d(2)-formaldehyde. The labeled peptides were
      combined and the peptide mixture was separated and fractionated by a strong
      cation exchange (SCX) column. Peptides from each SCX fraction were further
      separated by a microbore reversed-phase (RP) LC column. The effluents were then
      directly spotted onto a MALDI target using a heated droplet LC-MALDI interface.
      After mixing with a MALDI matrix, individual sample spots were analyzed by MALDI
      quadrupole time-of-flight MS, using an initial MS scan to quantify the dimethyl
      labeled peptide pairs. MS/MS analysis was then carried out on the peptide pairs
      having relative peak intensity changes of greater than 2-fold. The MS/MS spectra
      were subjected to database searching for protein identification. The search
      results were further confirmed by comparing the MS/MS spectra of the peptide
      pairs. Using this strategy, we detected and compared relative peak intensity
      changes of 5480 peptide pairs. Among them, 320 peptide pairs showed changes of
      greater than 2-fold. MS/MS analysis of these changing pairs led to the
      identification of 49 differentially expressed proteins between the parental SCC9
      cells and SCC9-E transfectants. These proteins were determined to be involved in
      different pathways regulating cytoskeletal organization, cell adhesion,
      epithelial polarity, and cell proliferation. The changes in protein expression
      were consistent with increased cell-cell and cell-matrix adhesion and decreased
      proliferation in SCC9-E cells, in line with E-cadherin tumor suppressor activity.
      Finally, the accuracy of the MS quantification and subcellular localization for 6
      differentially expressed proteins were validated by immunoblotting and
      immunofluorescence assays.

PMID- 16083296
TI  - Quantitative analysis of membrane proteins from breast cancer cell lines BT474
      and MCF7 using multistep solid phase mass tagging and 2D LC/MS.
AB  - We introduce a new multistep mass tagging technique and show its utility for
      reducing sample complexity when coupled with two-dimensional liquid
      chromatography/nano-electrospray ionization ion trap mass spectrometry (2D
      LC/nano ESI-MS). Solid-phase mass tagging reagents were used to identify and
      obtain relative quantitation of membrane proteins from two established breast
      cancer cell lines, BT474 and MCF7. The results presented in this study show that
      sample complexity can be reduced with corresponding increases in protein
      identification and quantitation.

PMID- 16083298
TI  - Comprehensive label-free method for the relative quantification of proteins from
      biological samples.
AB  - Pharmaceutical companies and regulatory agencies are broadly pursuing biomarkers
      as a means to increase the productivity of drug development. Quantifying
      differential levels of proteins from complex biological samples such as plasma or
      cerebrospinal fluid is one specific approach being used to identify markers of
      drug action, efficacy, toxicity, etc. We have developed a comprehensive, fully
      automated, and label-free approach to relative protein quantification from LC
      MS/MS experiments of proteolytic protein digests including: de-noising, mass and
      charge state estimation, chromatographic alignment, and peptide quantification
      via integration of extracted ion chromatograms. Results from a variance
      components study of the entire method indicate that most of the variability is
      attributable to the LC-MS injection, with a median peptide LC-MS injection
      coefficient of variation of 8% on a ThermoFinnigan LTQ mass spectrometer. Spiked
      recovery results suggest a quantifiable range of approximately 32-fold for a
      sample protein.

PMID- 16083297
TI  - Increased protein identification capabilities through novel tandem MS calibration
      strategies.
AB  - High mass measurement accuracy is critical for confident protein identification
      and characterization in proteomics research. Fourier transform ion cyclotron
      resonance (FTICR) mass spectrometry is a unique technique which can provide
      unparalleled mass accuracy and resolving power. However, the mass measurement
      accuracy of FTICR-MS can be affected by space charge effects. Here, we present a
      novel internal calibrant-free calibration method that corrects for space charge
      induced frequency shifts in FTICR fragment spectra called Calibration
      Optimization on Fragment Ions (COFI). This new strategy utilizes the information
      from fixed mass differences between two neighboring peptide fragment ions (such
      as y(1) and y(2)) to correct the frequency shift after data collection. COFI has
      been successfully applied to LC-FTICR fragmentation data. Mascot MS/MS ion search
      data demonstrate that most of the fragments from BSA tryptic digested peptides
      can be identified using a much lower mass tolerance window after applying COFI to
      LC-FTICR-MS/MS of BSA tryptic digest. Furthermore, COFI has been used for
      multiplexed LC-CID-FTICR-MS which is an attractive technique because of its
      increased duty cycle and dynamic range. After the application of COFI to a
      multiplexed LC-CID-FTICR-MS of BSA tryptic digest, we achieved an average
      measured mass accuracy of 2.49 ppm for all the identified BSA fragments.

PMID- 16083299
TI  - Parallel profiling of active transcription factors using an oligonucleotide array
      based transcription factor assay (OATFA).
AB  - Cell/tissue-specific gene expression are tightly regulated by various
      combinations of multiple transcription factors (TFs). Here, we present an
      oligonucleotide array-based transcription factor assay (OATFA), which allows the
      simultaneous assay of multiple active TFs. In this proof-of-principle work, both
      purified TFs and cell extracts were analyzed using OATFA and further antibody
      based validation confirmed the chip data. This method could simplify the assay of
      multiple TFs and may facilitate high-throughput profiling of large numbers of
      TFs.

PMID- 16083300
TI  - Challenges in preventing pyelonephritis in pregnant women in Indigenous
      communities.
AB  - INTRODUCTION:  AIM: To measure the quality of antenatal care in rural and remote
      regions of the Northern Territory, using asymptomatic bacteruria as an indicator.
      BACKGROUND: Indigenous Australian women and their babies have a greater frequency
      of adverse outcomes in pregnancy than their non-Indigenous counterparts. It is
      well established that asymptomatic bacteriuria may have serious outcomes in
      pregnancy, including an increased risk of pyelonephritis and a strong association
      with preterm and low birth weight delivery. Ensuring good quality antenatal care
      can reduce the individual risks of pregnancy for mothers and their babies. In the
      Northern Territory there are well established guidelines for antenatal care in
      rural and remote Indigenous communities. These are documented in the Women's
      Business Manual. Audit and feedback is one method that has been shown to have a
      small to moderate effect in changing clinician behaviour, in this case improving
      compliance with guidelines. METHODS: A retrospective chart audit of antenatal
      clients was conducted at 10 rural and remote primary health care clinics in the
      Northern Territory, Australia. The audit reviewed all the available charts (n =
      268) of pregnant women, from the participating communities, who gave birth in
      2002 or 2003. The diagnosis and management of asymptomatic bacteriuria was chosen
      as the indicator of quality antenatal care, as it is one of five areas of
      antenatal care where there is evidence that appropriate management improves
      outcomes. The quality of care was measured against the local guidelines, the
      Women's Business Manual. RESULTS: Women frequently had urine tests with where the
      dipstick showed an abnormal result, with 75% (95% CI [0.70,0.80]) of women having
      at least one episode of abnormal urinalysis during pregnancy. Six hundred and
      twenty episodes of abnormal urinalysis in pregnancy were identified. The
      incidence of bacteriuria at first visit was 16%, (95%-confidence interval = 95%
      CI [0.10, 0.21]). Compliance with the guidelines was poor. Fifty-six percent (95%
      CI [0.52,0.60]) of those samples testing positive on urinalysis were not sent to
      pathology for microscopy and culture, as recommended in the guidelines. Of those
      with a positive culture, 32% (95% CI 0.28,0.39) were appropriately treated with
      antibiotics. When antibiotics were given, good compliance of 82% (95% CI
      0.76,0.87) with antibiotic guidelines was demonstrated. The positive predictive
      value of dipstick urinalysis in diagnosing asymptomatic bacteriuria was low in
      this study at 33.5%. There were 13 episodes of confirmed or probable
      pyelonephritis. No women with recurrent urinary tract infections were followed up
      according to protocol. CONCLUSION: Aboriginal women have worse pregnancy outcomes
      than the non-Indigenous population of Australia. Pyelonephritis is a preventable
      condition in pregnancy. In these rural and remote communities, pyelonephritis has
      not been prevented due, in part, to a failure to follow the local guidelines.
      Structural problems were identified and need to be addressed in order to improve
      compliance with guidelines and hence pregnancy outcomes for rural and remote
      Indigenous women.

PMID- 16083301
TI  - Decreased expression of peroxisome proliferator-activated receptor gamma in
      endotoxin-induced acute lung injury.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR- gamma), a member of the
      nuclear hormone receptor superfamily of ligand-activated transcription factors,
      possesses anti-inflammatory properties. The purpose of the present study was to
      investigate the profile of PPAR-gamma expression in the lung and to explore its
      functional significance in lipopolysaccharide (LPS)-induced acute lung injury.
      Thirty male Wistar rats were randomly assigned to one of the following five
      groups: saline control group and different LPS groups (2 h, 4 h, 6 h and 8 h
      after LPS 6 mg/kg i.v.). At predefined time points, blood samples were collected
      to measure plasma level of tumor necrosis factor (TNF)-alpha and lungs were
      removed to assay histopathological changes, wet-to-dry weight (W/D) ratio,
      myeloperoxidase (MPO) activity and TNF-alpha level. Expression of PPAR-gamma and
      activation of nuclear factor (NF)-kapaB p65 in lung tissues were also examined in
      each group. LPS injection resulted in marked lung damage and elevated levels of
      W/D ratio and MPO activity in the lung. Increased levels of TNF-alpha were also
      observed in the plasma and lung. These inflammatory events were associated with
      reduced expression of PPAR-gamma protein and with activation of NF-kapaB in the
      lung. Our data suggest that decreased expression of PPAR-gamma protein in lungs
      may contribute to the ongoing pulmonary inflammation and tissue injury in
      endotoxemia.

PMID- 16083302
TI  - Baroreflex sensitivity as an individual characteristic feature.
AB  - The reproducibility of baroreflex sensitivity (BRS in ms/mmHg; BRSf in mHz/mmHg)
      determined with respect to the coherence between the variability in systolic
      blood pressure (SBP) and inter-beat intervals (IBI) or heart rate (HR) was
      tested. SBP and IBI were recorded beat-to-beat for 5 min (Finapres, breathing at
      0.33 Hz) in 116 subjects (aged 19-24 years) sitting at rest three times in
      periods of one week. BRS and BRSf was determined by a cross-spectral method in a
      frequency range of 0.067-0.133 Hz. Eight indices were evaluated: BRS(0.1 Hz)
      /BRSf(0.1 Hz) - the value at a frequency of 0.1 Hz; BRS(COHmax)/BRSf(COHmax) -
      the value at maximum coherence; BRS(Wcoh)/BRSf - weighted value with respect to
      coherence values in the whole frequency range; BRS(WPcoh)/BRS(WPcoh) - weighted
      value with respect to coherence for frequencies with coherence above 0.5. All
      indices revealed a lower intraindividual than interindividual variability
      (p<0.001). The individual mean values of BRS or BRSf correlated (p<0.001) with
      standard deviation of their individual values for all indices. Baroreflex
      sensitivity is an individual characteristic feature with the highest
      reproducibility at its low values in spite of its resting variation.
      Reproducibility is not influenced by modification of the spectral method used.

PMID- 16083303
TI  - Selective inhibition of brain Na,K-ATPase by drugs.
AB  - The effect of drugs from the class of cardiac (methyldigoxin, verapamil,
      propranolol), antiepileptic (carbamazepine), sedative (diazepam) and
      antihistaminic (promethazine) drugs on Na,K-ATPase activity of plasma membranes
      was studied in rat brain synaptosomes. Methyldigoxin in a concentration of 0.1
      mmol/l inhibits enzyme activity by 80 %. Verapamil, propranolol and promethazine
      in concentrations of 20, 20 and 2 mmol/l respectively, entirely inhibit the
      ATPase activity. Carbamazepine and diazepam in concentrations of 0.02-60 mmol/l
      have no effect on the activity of this enzyme. According to the drug
      concentrations that inhibit 50 % of enzyme activity (IC(50)), the potency can be
      listed in the following order: methyldigoxin promethazine verapamil ?
      propranolol. From the inhibition of commercially available purified Na,K-ATPase
      isolated from porcine cerebral cortex in the presence of chosen drugs, as well as
      from kinetic studies on synaptosomal plasma membranes, it may be concluded that
      the drugs inhibit enzyme activity, partly by acting directly on the enzyme
      proteins. Propranolol, verapamil and promethazine inhibitions acted in an
      uncompetitive manner. The results suggest that these three drugs may contribute
      to neurological dysfunctions and indicate the necessity to take into
      consideration the side effects of the investigated drugs during the treatment of
      various pathological conditions.

PMID- 16083304
TI  - Red wine polyphenols prevent endothelial damage induced by CCl4 administration.
AB  - It became evident in the present study that carbon tetrachloride (CCl(4)), in
      addition to its known liver and renal toxicity, causes serious damage to
      endothelial cells. The preventive effect of red wine on cardiovascular diseases
      has been documented in a number of human population studies as well as in animal
      experimental models. In this study, the endothelium protective effect of
      polyphenolic compounds isolated from red wine was studied in rats administered
      0.5 ml of CC(4)/kg body weight intraperitoneally twice a week for 8 weeks.
      Endothelemia (endothelial cells/10 microl of plasma) was used as the marker of
      endothelial cell injury in vivo. Chronic CCl(4) treatment for 8 weeks lead to a 3
      fold increase of free endothelial cells circulating in the blood when compared to
      the baseline values (2.5+/-0.3). Parallel oral administration of polyphenols 40
      mg/kg/day significantly decreased the endothelemia. Polyphenolic compounds alone
      did not produce significant changes. Three weeks of spontaneous recovery after
      the 8-week treatment with CCl(4) did not lead to a marked decrease of
      endothelemia, but the administration of red wine polyphenols during the 3-week
      period significantly decreased free endothelial cells in the blood. It can be
      concluded that long-term administration of CCl(4) may serve as a useful
      experimental model of endothelial damage. The red wine polyphenolic compounds
      exert a powerful protective effect on endothelial cells from the injury caused by
      CCl(4). This effect was documented by decreased endothelemia that corresponded to
      diminished endothelial cell swelling and detachment evaluated by histology of the
      vascular intima. The endothelium protective effect may be one of the key factors
      that contribute to the preventive action of red wine on cardiovascular diseases.

PMID- 16083305
TI  - Effects of human soluble BAFF synthesized in Escherichia coli on CD4+ and CD8+ T
      lymphocytes as well as NK cells in mice.
AB  - B cell-activating factor belonging to the TNF family (BAFF, also called BLyS,
      TALL-1, zTNF-4, or THANK) is an important survival factor for B lymphocytes. In
      this study, we injected mouse abdominal cavity with human soluble BAFF (hsBAFF,
      0.01, 0.1, 0.5, 2 mg/kg body mass) synthesized in Escherichia coli. On the 8th
      day after injection, we investigated the effects of hsBAFF on immune functional
      activities of splenic B lymphocytes, CD4(+) and CD8(+) T lymphocytes and natural
      killer (NK) cells in mice. The results showed that B lymphocyte proliferation
      significantly increased in hsBAFF-treated groups with dosages of 0.1 mg/kg
      (p<0.05), 0.5 and 2 mg/kg (p<0.01). We observed a dose-dependent increase of
      CD4(+) T lymphocyte percentage and significantly higher values in 0.5 and 2 mg/kg
      hsBAFF-treated groups (p<0.05 and p<0.001, respectively) compared to control
      group, but CD8(+) T lymphocyte percentage remained unchanged. The ratio of CD4(+)
      to CD8(+) T lymphocytes rose with increasing hsBAFF dosage (p<0.05 for 2 mg/kg
      hsBAFF vs. control). Significantly stronger NK cell activities were found in 0.5
      and 2 mg/kg hsBAFF-treated groups (p<0.05). The main finding of this study is
      that the hsBAFF can enhance immune responses in the body by increasing B
      lymphocyte and CD4(+) T lymphocyte function as well as elevating NK cell
      activity.

PMID- 16083306
TI  - The influence of very-low-calorie-diet on serum leptin, soluble leptin receptor,
      adiponectin and resistin levels in obese women.
AB  - The aim of our study was to determine whether adipocyte-derived hormones leptin,
      adiponectin and resistin contribute to the improvement of insulin sensitivity
      after very-low calorie diet (VLCD). Therefore, serum levels of these hormones
      were measured in fourteen obese females before and after three weeks VLCD and in
      seventeen age- and sex-matched healthy controls. Body mass index, HOMA index,
      serum insulin and leptin levels in obese women before VLCD were significantly
      higher than in control group (BMI 48.01+/-2.02 vs. 21.38+/-0.42 kg/m(2), HOMA
      10.72+/-2.03 vs. 4.69+/-0.42, insulin 38.63+/-5.10 vs. 18.76+/-1.90 microIU/ml,
      leptin 77.87+/-8.98 vs. 8.82+/-1.52 ng/ml). In contrast, serum adiponectin and
      soluble leptin receptors levels were significantly lower in obese women before
      VLCD than in the control group. No differences were found in serum glucose and
      resistin levels between the obese group before VLCD and the control group. VLCD
      significantly decreased BMI, HOMA index, serum glucose, insulin and leptin levels
      and increased soluble leptin receptor levels. The changes in serum adiponectin
      and resistin levels in obese women after VLCD did not reach statistical
      significance. We conclude that leptin and soluble leptin receptor levels were
      affected by VLCD while adiponectin and resistin concentrations were not.
      Therefore, other mechanisms rather than changes in the endocrine function of the
      adipose tissue are probably involved in the VLCD-induced improvement of insulin
      sensitivity.

PMID- 16083307
TI  - Temporal profile of ultrastructural changes in cortical neurones after a
      compression lesion.
AB  - We studied the occurrence of apoptosis and secondary delayed cell death at
      various time points in the penumbra zone, which is the target for therapeutic
      intervention after stroke. A compression lesion was induced in the right sensory
      motor cortex of rat brains. At 0.5, 1, 3, 6, 12, 24, 48 and 72 h after lesioning,
      motor functions were evaluated by behavioral tests, and cortical layers IV and V
      were examined by electron microscopy. Behavioral recovery was observed at 48 h
      after lesioning. At 0.5-1 h in the lesioned area, the neuropil was expanded and
      contained affected cells. Apoptotic cells were found between 0.5-72 h, and at 12
      h, 47.3 % of the total cell number was apoptotic cells. On the contralateral
      side, cells showed an enlarged endoplasmic reticulum at 3 h, indicating secondary
      delayed cell death. Our results show that a compression lesion is a useful model
      for studying ultrastructural changes in injured cells. The lesion results in the
      penumbra zone with apoptotic cell death between 0.5-72 h. As secondary delayed
      cell death occurred on the contralateral side at three hours after lesioning
      might be the time period during which injured, but still viable, neurons can be
      targets for acute treatment.

PMID- 16083308
TI  - Insulin resistance is not related to plasma homocysteine concentration in healthy
      premenapausal women.
AB  - This study was performed to test whether plasma homocysteine concentrations are
      related to insulin resistance in healthy premenopausal women. For this purpose,
      the relationship between insulin resistance (as assessed by HOMA index) and
      fasting plasma homocysteine level was determined in 83 healthy volunteers. The
      results indicated that homocysteine concentrations did not vary as a function of
      HOMA index (r = -0.147). Plasma homocysteine concentrations also did not vary as
      a function of other parameters of insulin resistance such as HDL-cholesterol and
      triglycerides, which they correlated inversely with body mass index (BMI).
      Furthermore, when individuals were classified according to quartiles of insulin
      resistance (HOMA index), plasma homocysteine concentrations from the lowest to
      the highest quartiles were not significantly different. On the other hand, the
      HOMA index correlated significantly with triglyceride concentrations (r = 0.377,
      p< 0.001), HDL-cholesterol (r = -0.310, p< 0.01) and BMI (r = 0.468, p< 0.001).
      These results suggest that plasma homocysteine concentrations are not related to
      insulin resistance and/or metabolic abnormalities associated with it in
      premenopausal women.

PMID- 16083309
TI  - Effect of cardiac lymph flow obstruction on cardiac collagen synthesis and
      interstitial fibrosis.
AB  - The effect of chronic cardiac lymphatic obstruction on the myocardial synthesis
      of collagen type I and III was investigated in a rabbit model. In the lymphatic
      obstruction group (n=16), plasma C-terminal propeptide type I procollagen (PICP)
      and N-terminal propeptide type III procollagen (PIIINP) were elevated at 7, 14
      and 30 days after the operation (p<0.05). The elevated PICP and PIIINP returned
      to the pre-operation values 60 days after the operation. The myocardial
      expression of collagen type I and III mRNA were also enhanced in the lymphatic
      flow obstruction group. Plasma PICP, PIIINP and myocardial collagen type I and
      III mRNA remained unchanged in the control group (n=16). We concluded that
      chronic obstruction of cardiac lymph flow leads to enhanced myocardial collagen
      synthesis in rabbits. The enhanced collagen synthesis starts within seven days
      after lymphatic obstruction and subsides after 60 days.

PMID- 16083310
TI  - Inhibition of vascular endothelial growth factor-induced retinal
      neovascularization by retinoic acid in experimental retinopathy of prematurity.
AB  - Vascular endothelial growth factor (VEGF) has an important role in the
      pathogenesis of retinopathy of prematurity (ROP) and inhibition of VEGF
      expression in the neovascular phase might prevent destructive neovascularization
      in ROP. It is suggested that retinoids exert a highly potent antiangiogenic
      activity by inhibiting VEGF expression. The aim of this study was to demonstrate
      the preventive effect of retinoic acid (RA) on the VEGF-induced retinal
      neovascularization in a rat model of ROP. Wistar albino rats were placed into
      incubators at birth and exposed to an atmosphere alternating between 50 % and 10
      % O(2) every 24 hours. After 14 days, the animals were removed to room air and
      received either an intraperitoneal injection of RA (5 mg/kg/day) (n=9) or saline
      (n=4) daily for six days, and sacrificed at 21 days. Other rats (n=4) were raised
      in room air and served as age-matched controls. The globe of each eye was cut
      through the cornea and embedded in paraffin. Serial sections were stained with
      hematoxylin-eosin for quantification of neovascular nuclei. The avidin-biotin
      peroxidase method was performed for evaluation of VEGF expression. The average
      number of neovascular nuclei was significantly lower in the control group
      compared to that in the ROP groups. In addition, it significantly decreased in
      the RA-treated ROP group compared to that of the saline-administrated ROP group.
      VEGF immunostaining was overall negative in room air-exposed rats. The VEGF
      immunostaining score significantly decreased in the RA-treated ROP group compared
      to that in the saline-administered ROP group. RA treatment might be beneficial in
      preventing neovascularization resulting from oxygen-induced retinopathy by
      downregulation of VEGF expression.

PMID- 16083311
TI  - Comparison of the phospholipid and triacylglycerol fatty acid profile of rat
      serum, skeletal muscle and heart.
AB  - Although several studies have analyzed the fatty acid profile of phospholipids
      (PL) and, to a lesser degree, triacylglycerols (TG) in one or more tissues
      concurrently, a systematic comparison of the fatty acid composition of different
      tissues and/or lipid classes is lacking. The purpose of the present study was to
      compare the fatty acid composition of major lipid classes (PL and TG) in the rat
      serum, soleus muscle, extensor digitorum longus muscle and the heart. Lipids were
      extracted from these tissues and analyzed by a combination of thin-layer
      chromatography and gas chromatography. We found many significant differences in
      various tissues and lipid classes. Serum had the most distinct fatty acid profile
      in PL but this "uniqueness" was less apparent in TG, where differences among
      tissues were in general less frequent than in PL. These two skeletal muscles
      exhibited similar fatty acid composition in both lipid classes despite their
      different muscle fiber type composition, denoting that fiber type is not a major
      determinant of the fatty acid composition of rat skeletal muscle. The fatty acid
      profile of heart PL was the most different from that of the other tissues
      examined. PL were rich in polyunsaturated fatty acids, whereas TG were rich in
      monounsaturated fatty acids. Although the reasons for the differences in fatty
      acid profile among the tissues examined are largely unknown, it is likely that
      these differences have an impact upon numerous biological functions.

PMID- 16083312
TI  - Cytogenetic and immunological changes after dermal exposure to polycyclic
      aromatic hydrocarbons and UV radiation.
AB  - Goeckerman's therapy (GT), which combines exposure to coal tar (polycyclic
      aromatic hydrocarbons - PAHs) and UV radiation (UV) is often used as the first
      option for treatment of psoriasis. However, PAHs and UV represent mutagenic,
      carcinogenic and immunotoxic agents. Therefore GT can represent a health risk for
      the patients. The group under observation consisted of thirty patients undergoing
      GT. Before and after the treatment, blood samples were collected and chromosomal
      aberrations and selected immunological markers were determined. The relationships
      between chromosomal aberrations and immunological markers and the extent
      (duration) of exposure to GT were evaluated. The Psoriasis Area and Severity
      Index (PASI) score confirmed the high efficacy of GT. However, significantly
      elevated levels of chromosomal aberrations of peripheral lymphocytes were also
      found after the therapy (p<0.001). The levels of chromosomal abnormalities
      correlated to the extent and the total duration of exposure to PAHs (r = 0.682,
      p<0.01 and r = 0.605, p<0.05). After the therapy, significantly decreased levels
      of IgE, IgM isotypes of immunoglobulin, alpha(2)-macroglobulin and transferrin
      together with beta(2)-microglobulin were found. From the immunological markers
      listed above only the decreased level of alpha(2)-macroglobulin correlated to the
      extent of exposure to PAHs (r = -0.568, p<0.05). No correlation was found between
      chromosomal aberrations, significantly changed immunological markers and the
      duration of UV exposure. Our study revealed that GT has a significant impact on
      both genetic and immunological parameters of psoriatic patients. The results
      indicate that GT could increase genotoxic risk and modulates immunity of treated
      patients.

PMID- 16083313
TI  - Pulmonary protective effects of hyberbaric oxygen and N-acetylcysteine treatment
      in necrotizing pancreatitis.
AB  - The purpose of this study is to analyze the protective effect of combining N
      acetylcysteine (NAC) and hyberbaric oxygen (HBO) treatment in the lung tissue
      during acute pancreatitis. Sixty Sprague-Dawley male rats were randomly divided
      into five groups; Group I; Control group (n=12), Group II; pancreatitis group
      (n=12), Group III; pancreatitis + NAC treatment group (n=12), Group IV;
      pancreatitis + HBO treatment group (n=12), Group V; pancreatitis + HBO + NAC
      treatment group (n=12). HBO was applied postoperatively for 5 days, twice a day
      at 2.5 fold absolute atmospheric pressure for 90 min. Lung tissue was obtained
      for measuring malondialdehyde (MDA), superoxide dismutase (Cu/Zn-SOD) and
      glutathione peroxidase (GSH-Px) levels along with histopathological tissue
      examinations. This study showed that all three treated groups (HBO alone, NAC
      alone and combined HBO+NAC treatment) had pulmonary protective effects during
      acute necrotizing pancreatitis.

PMID- 16083314
TI  - Erythropoietin attenuates lipopolysaccharide-induced splenic and thymic apoptosis
      in rats.
AB  - Apoptosis of lymphoid tissues during sepsis is well documented and linked to the
      pathobiology of organ failure and death. In this study, we evaluated the effect
      of a single dose of recombinant erythropoietin (EPO) on thymic and splenic
      apoptosis in an endotoxic sepsis model. Young male Wistar rats were divided into
      3 groups and administered intraperitoneally (IP) either normal saline;
      lipopolysaccharide (LPS) 10 mg/kg; or EPO (5000 U/kg) 30 min before
      lipopolysaccharide. Six hours following LPS administration animals were
      sacrificed. Apoptosis was assessed by hematoxylin-eosin staining, terminal
      deoxynucleotide transferase-mediated fluorescein-dUTP nick end labeling (TUNEL),
      and caspase-3 immunostaining. When compared with animals given LPS, animals
      pretreated with EPO displayed reduced splenic and thymic TUNEL positivity of 44+/
      3 (p<0.05) and 143+/-4 (p<0.05) nuclei per high power field (hpf), respectively.
      Caspase-3 positivity was also significantly reduced in the spleen and thymus,
      with 31+/-4 (p<0.05) and 93+/-3 (p<0.05) positive stained nuclei per hpf,
      respectively. Serum nitrite levels were elevated in animals given
      lipopolysaccharide. Pretreatment with EPO attenuated the increase in nitrite
      levels; however, this did not reach statistical significance. We conclude that a
      single dose of recombinant erythropoietin can reduce thymic and splenic apoptosis
      associated with lipopolysaccharide administration.

PMID- 16083315
TI  - Keynote Presentation at the Eight International Congress of Behavioral Medicine:
      the Pittsburgh common cold studies: psychosocial predictors of susceptibility to
      respiratory infectious illness.
AB  - This article provides a selected overview of 20 years of research on the role of
      psychosocial factors in susceptibility to upper respiratory infections. We
      present evidence from our laboratory that psychological stress is associated with
      increased risk for developing respiratory illness for persons intentionally
      exposed to a common cold virus, that the longer the duration of the stressor the
      greater the risk, and that stress association with susceptibility may be mediated
      by stress-induced disruption of the regulation of proinflammatory cytokines. We
      further provide evidence that social relationships (social integration and social
      support) are also associated with risk for respiratory illness: Social
      integration is associated with reduced risk irrespective of stress level and
      social support protects persons from the pathogenic influences of stress.
      Finally, we report recent evidence that lower levels of early childhood
      socioeconomic status (SES) are associated with greater risk of viral-induced
      illness during adulthood, independent of adult SES.

PMID- 16083317
TI  - Hostility, conflict and cardiovascular responses in married couples: a focus on
      the dyad.
AB  - This study examined the relations of one's own total trait hostility and one's
      spouse's hostility as influences on cardiovascular (CV) responses to couple
      interactions (including conflict discussions) in 45 married couples aged 24-50.
      Systolic blood pressure and cardiac index (CI) reactivity to conflict discussion
      and recovery after conflict was greater in low hostile males if they were
      interacting with high hostile wives (p < .02). Vascular resistance index (VRI)
      reactivity to interactions was greater in high hostile husbands with high hostile
      wives (p < .05). Women showed no adverse CV effects of having a hostile spouse
      when their own hostility was low. Instead, seeming to anticipate the subsequent
      couple interactions, wives from duos in which both partners were high in
      hostility had higher baseline VRI levels and lower baseline CI compared to wives
      from duos in which both were low in hostility (ps < .05), and they simply
      maintained these group differences with no greater CV reactivity during the
      interactions. Findings suggest that CV responses before, during, and after
      marital discussions, particularly those characterized by conflict, may be
      influenced not only by one's own hostility but by the hostility of one's partner
      as well.

PMID- 16083316
TI  - Psychosocial considerations in the European guidelines for prevention of
      cardiovascular diseases in clinical practice: Third Joint Task Force.
AB  - The International Society of Behavioral Medicine (ISBM) was one of eight
      societies that comprised the Third Task Force of European and Other Societies on
      Prevention of Cardiovascular Disease in Clinical Practice (2003-2004). This task
      force considered published knowledge from diverse fields related to preventive
      cardiology including behavioral medicine to improve risk estimation and risk
      factor management. The scientific evidence supporting the guidelines included
      findings on low socioeconomic status, social isolation, psychosocial stress,
      hostility, depression and negative affect, the clustering of psychosocial and
      lifestyle risk factors, and lifestyle psychosocial interventions. Recommendations
      for promoting behavior change and management of psychosocial and lifestyle
      factors in clinical practice include strategies for promoting healthy lifestyle,
      improving health care provider-patient interactions, implementing multimodal
      interventions, and managing psychosocial risk factors.

PMID- 16083318
TI  - Good self-rated health is related to psychosocial resources and a strong cortisol
      response to acute stress: the LiVicordia study of middle-aged men.
AB  - Self-rated health (SRH) is a strong predictor for disease and death. The
      relations among SRH, psychosocial factors, and cortisol dynamics were tested
      using pooled data from the LiVicordia study of 50-year-old men in Lithuania (n =
      94) and Sweden (n = 89), controlling for effect of residence. SRH was assessed by
      "How would you assess your own health?" A standardized laboratory stress test
      included measures of cortisol in serum and saliva. Good SRH related to high scale
      scores of decision latitude, social support at work, coping, self-esteem, and
      sense of coherence; to low scores of overcommitment (all p < .01) and vital
      exhaustion (r = -0.40, p < 0.001); to low concentrations of saliva baseline
      cortisol (r = -.26, p = .001); and to a strong cortisol response to stress (r =
      .27, p = .001). Findings that good SRH related to favorable psychosocial
      characteristics and to a dynamic cortisol stress response indicate a possible
      explanation for observed lower risk for disease and death in this state.

PMID- 16083319
TI  - Interleukin-1 may link helplessness-hopelessness with cancer progression: a
      proposed model.
AB  - A model of the relations between psychological factors and cancer progression
      should include brain and systemic components and their link with critical
      cellular stages in cancer progression. We present a psychoneuroimmunological
      (PNI) model that links helplessness-hopelessness (HH) with cancer progression via
      interleukin-1beta (IL-1beta). IL-1beta was elevated in the brain following
      exposure to inescapable shock, and HH was minimized by antagonizing cerebral IL
      1beta. Elevated cerebral IL-1beta increased cancer metastasis in animals.
      Inescapable shock was associated with systemic elevations of IL-1beta and
      peripheral IL-1beta was associated with escape from apoptosis, angiogenesis, and
      metastasis. Involvement of the sympathetic nervous system and the hypothalamic
      pituitary-adrenal axis are discussed. Future studies need to identify the role of
      additional factors in this PNI pathway.

PMID- 16083320
TI  - A brief review of the pathophysiology, associated pain, and psychosocial issues
      in sickle cell disease.
AB  - Sickle cell disease (SCD) is the most common genetic disorder of the blood. The
      disease produces significantly abnormal hemoglobin (Hgb) molecules in red blood
      cells (RBCs). The sickling of RBCs occurs when partially or totally deoxygenated
      Hgb molecules distort their normal disk shape, producing stiff, sticky, sickle
      shaped cells that obstruct small blood vessels and produce vasoocclusion as well
      as the disruption of oxygen to body tissues. Because tissue damage can occur at
      multiple foci, patients with SCD are at risk for other medical complications
      including, but not limited to, delayed growth and sexual maturation; acute and
      chronic pulmonary dysfunction; stroke; aseptic necrosis of the hip, shoulders, or
      both; sickle cell retinopathy; dermal ulcers; and severe chronic pain. The
      chronicity of the illness combined with frequent hospitalizations for pain and
      other medical management can contribute significantly to impaired psychosocial
      functioning, altered intra- and interpersonal relationships, and reduced quality
      of life. Unlike previous qualitative reviews of SCD, this article describes the
      relevant clinical and research data on the relation between psychosocial
      functioning and SCD in adult and child populations. The authors discuss the
      significant role of psychosocial issues in the trajectory and management of the
      disease and conclude that understanding the pathophysiology of SCD without
      thoroughly understanding the equally important psychosocial influences is
      misunderstanding SCD.

PMID- 16083321
TI  - Psychometric properties of the cervical smear belief inventory for Chinese women.
AB  - This study examines the reliability and validity of the scores of Cervical Smear
      Belief Inventory (CSBI) among Chinese women in Taiwan. Women who were nonadherent
      to cervical screening guidelines were recruited (N = 424). Reliabilities showed
      good internal consistency for the perceived Pros, Cons, and Susceptibility scales
      (a ranged from .78 to .87). Factor analysis showed good construct validity of the
      scores of CSBI that revealed concordant patterns with existing social and
      behavioral theories, except that the Norms scale was loaded with the Pros scale.
      Moreover, two items in the Cons scale appeared to be "cultural belief toward
      virginity." Item-discrimination analysis showed that all items in the CSBI
      successfully discriminated women with favorable cervical smear beliefs from those
      with unfavorable beliefs (p < .001). In summary, many psychometric properties of
      the CSBI showed that the scores of the inventory were reliable and valid to
      assess belief toward cervical smear among Chinese women.

PMID- 16083322
TI  - Divergent effects of active coping on psychological distress in the context of
      the job demands-control-support model: the roles of job control and social
      support.
AB  - This study examined the effects of active coping on psychological distress in the
      context of the job demands-control-support model. Participants were 726 male
      nonmanagers in a large electrical company in Japan. Hierarchical multiple
      regression analyses were conducted to examine whether active coping and coping
      resources (job control, supervisor support, and coworker support) have
      interaction effects on psychological distress. Active coping had an interaction
      effect with coworker support, whereas it did not with job control and supervisor
      support. Results suggest that coworker support can facilitate the effectiveness
      of active coping, whereas job control or supervisor support cannot.

PMID- 16083323
TI  - Some problems with life event lists and health outcomes.
AB  - Lists of life events are widely used in health outcomes research. As part of a
      large cohort study of women's health in Australia, age- and gender-specific life
      events lists were developed and administered to women in different age groups
      over time. In this article, we provide empirical evidence that recall of life
      events is subject to telescoping (i.e., remote events are reported to have
      occurred more recently) and to mood (women with lower mental health scores report
      more life events, especially perceived rather than factual events). Nevertheless,
      even after adjustment for confounders, there is a clear association between
      poorer physical health and more life events. Therefore, these results demonstrate
      a continuing need for lists of life events in health research but also highlight
      the methodological challenges in using them.

PMID- 16083325
TI  - Malaria vaccines in development.
AB  - The recent infusion of public and private funding for malaria vaccine development
      has greatly accelerated the pace at which candidate malaria vaccines are entering
      the clinic. Recent promising results from vaccine trials carried out in malaria
      naive and -endemic populations have revealed important insights into what will be
      required of a successful vaccine. Significant challenges lie ahead, not the least
      of which is insuring access of a malaria vaccine to the populations that need it
      most. Creative strategies, strong partnerships with developing countries,
      industry-like approaches to product development, and political vision and
      leadership on the part of wealthy nations will be critical to the successful
      implementation of this important new tool to reduce the intolerable burden of
      malaria.

PMID- 16083326
TI  - Emerging drugs for ocular allergy.
AB  - Ocular allergy is a common condition that usually affects the conjunctiva of the
      eye and is, therefore, often referred to as allergic conjunctivitis. The severity
      of the disease can range from mild itching and redness, as seen in seasonal
      allergic conjunctivitis, to the more severe, sight-threatening forms such as
      vernal and atopic keratoconjunctivitis. The central mechanism in the pathogenesis
      of these diseases is IgE-mediated mast cell degranulation and activation of T
      lymphocytes, eosinophils and conjunctival structural cells. The pharmacotherapy
      of allergic conjunctivitis consists of several classes of drugs: antihistamines,
      mast cell stabilisers, dual-acting agents and corticosteroids. None of the
      available drugs completely abolishes the development of ocular allergy. For this
      reason, new topical antiallergic/anti-inflammatory agents are currently and
      continually under clinical trials. This review provides a background to ocular
      allergic diseases, the medical need for therapy and current and potential new
      treatments.

PMID- 16083327
TI  - Autism spectrum disorders: emerging pharmacotherapy.
AB  - Autism, Asperger and other pervasive developmental disorders (PDDs) are an
      increasingly commonly identified group of conditions wherein patients experience
      significant difficulty in social interactions, communicating with others, and
      inflexible adherence to unusual, unhelpful and frequently stereotyped routines
      and behaviour. These autism spectrum disorders are now being diagnosed earlier in
      life (approximately 15 months), and often remain a chronic, daily burden for
      those afflicted. In addition to the often profound impact on an individual's
      quality of life, the familial, social and economic burdens of PDDs can be
      enormous. No treatments are curative, and most pharmacological treatments are
      employed to treat specific troubling symptoms rather than the core features of
      the disorder itself. Therefore, more effective pharmacotherapies are desperately
      needed. This review describes current and emerging pharmacotherapies that may
      advance care of people with PDDs.

PMID- 16083328
TI  - Emerging drugs for restless legs syndrome.
AB  - Restless legs syndrome (RLS) is a common, but often underdiagnosed, neurological
      disorder, which is characterised by an imperative urge to move the extremities
      associated with paraesthesias, worsening of symptoms at rest and in the evening
      or at night, and, as a consequence, sleep disturbances. RLS affects 1-10% of the
      population. The aetiology of RLS is unknown, but besides genetic factors the
      dopaminergic and opioidergic system may play a crucial role and new developments
      also point to an exciting iron-dopamine connection in the pathophysiology of this
      burdening disorder. Due to the limited disease-specific knowledge, current
      treatment strategies are not curative, but nevertheless may produce an effective
      and lasting relief of symptoms. Although clinically based treatment has focused
      on levodopa, opioids and benzodiazepines for a long time, evidence-based and
      clinical guidelines identify dopamine agonists as a first-line treatment for
      daily restless legs symptoms. These substances are now in the process of
      registration for this indication. Ropinirole is the first dopamine agonist that
      has been approved by the FDA in May 2005. In addition, several promising new
      therapies with nondopamine profiles are under development for RLS.

PMID- 16083329
TI  - The development of erythropoietic agents in oncology.
AB  - The erythropoietic agents have achieved a remarkable degree of success as
      products for the treatment of anaemia associated with cancer chemotherapy. Three
      agents, epoetin-alpha, epoetin-beta and darbepoetin-alpha, share this global
      market and have demonstrated similar efficacy and share similar shortcomings,
      primarily a lower magnitude of cost/benefit than is the case for the dialysis
      patient. The continued success of these agents will depend on their ability to
      address the issue of resistance to therapy in the cancer setting, with the most
      promising and practical initiatives including cotherapy with parenteral iron, and
      earlier initiation of therapy. Recently, safety issues have arisen with respect
      to these agents in the cancer setting, particularly focused on possible promotion
      of tumour progression. A large body of data suggests that these agents are safe
      when used in accordance with the package inserts. The data bearing upon these
      issues will be reviewed and three new agents entering clinical development will
      be described.

PMID- 16083330
TI  - Emerging drugs for the treatment of myelodysplastic syndrome.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal
      haematopoietic stem cell disorders characterised by ineffective haematopoiesis
      and an increased risk of developing acute myeloid leukaemia. At present, the only
      curative option is allogeneic stem cell transplantation. However, the majority of
      patients are not eligible for this therapy, due to excessive treatment-related
      morbidity and mortality or lack of a suitable donor. As a result, the need for
      alternative therapies is great. Our improved understanding of the molecular
      pathogenesis of MDS has resulted in several new promising therapeutic agents.
      This review will consider the rational development of new agents based on the
      molecular biology of MDS.

PMID- 16083331
TI  - Emerging drugs for adult acute lymphoblastic leukaemia.
AB  - Although most patients with adult acute lymphoblastic leukaemia (ALL) can achieve
      a remission when treated with conventional, DNA-damaging chemotherapy, in more
      than half of all cases the disease relapses and ultimately results in death.
      Therefore, there is a substantial need for new antileukaemic drugs. Recent
      advances in the understanding of the molecular alterations in ALL have lead to
      the identification of new targets and the arrival of molecular-targeted therapies
      in the clinical setting. The prototype for this approach is the treatment of
      Philadelphia chromosome-positive ALL with imatinib mesylate. Here, the targeting
      of a molecular abnormality--inhibition of BCR-ABL tyrosine kinase--has turned a
      very poor-prognosis disease into one in which promising results are achieved.
      Promising new therapies are under development that target various goals,
      including the NOTCH signalling pathway, purine nucleoside phosphorylase activity,
      mammalian target of rapamycin and tyrosine kinase. This review outlines recent
      advances in the development of emerging drugs for the treatment of adult ALL. The
      recent advances in the understanding of the biology and pathogenesis of ALL have
      helped to determine prognosis and to plan the therapy of adult patients with ALL.
      Still, despite improved complete remission rates of 65-90% with current therapy,
      only 20-40% of patients can be considered cured. New therapeutic alternatives are
      needed to improve these results. With a better understanding of the disease, more
      target-specific therapies could be designed. The aim of this review is to
      highlight new pharmacotherapies and those emerging drug treatments for patients
      with adult ALL.

PMID- 16083332
TI  - Treatment of menopausal symptoms post-Women's Health Initiative: refinement of
      existing treatments and development of new therapies.
AB  - Menopause is a normal life transition for women. More than 80% of women
      experience some symptoms at menopause and > 25% of women in western countries
      seek treatment for a variety of symptoms that accompany this transition. In
      addition, there are certain chronic disease processes that accelerate after the
      menopausal transition. Hormone replacement therapy (HRT) with various
      combinations of oestrogen and progesterone compounds has been the mainstay of
      treatment for menopausal symptoms, as well as theoretical reduction in
      acceleration of certain chronic diseases after menopause. After the publication
      of the results of the Women's Health Initiative study in June 2002, the safety of
      HRT, as well as its effectiveness in decreasing various chronic diseases, was
      challenged. New formulations of hormone therapy, as well as new treatments, are
      evolving to aid the reduction of menopausal symptoms and long-term risks of
      common chronic disease processes that accelerate after the menopause.

PMID- 16083333
TI  - Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical
      pipelines.
AB  - Obesity is associated with hypertension, diabetes, dyslipidaemias and metabolic
      syndrome, and causes substantial morbidity and mortality from cardiovascular and
      other diseases. The cost to treat obesity and its complications in the US has
      increased steeply and is currently estimated to be USD 100 billion. Current
      therapy for obesity is mainly based on changes in lifestyle that often fail.
      Existing pharmacological treatment is marginally efficient and poorly tolerated.
      The discovery of leptin and related neural mechanisms of energy metabolism
      regulation has opened the doors to potential targets for new antiobesity drugs.
      In this review, new pharmacological targets are discussed and an update on the
      development of emerging antiobesity drugs is provided. Despite intense
      investigation, the pipelines for antiobesity drugs in late stages of development
      are relatively empty. Breakthrough treatments for obesity may take some years to
      emerge. Clinical trials will be necessary to clarify the impact of new
      antiobesity drugs on hard cardiovascular and metabolic end points.

PMID- 16083334
TI  - Nonalcoholic fatty liver disease: a review.
AB  - Nonalcoholic fatty liver disease is an umbrella term that includes steatosis,
      nonalcoholic steatohepatitis and advanced fibrosis or cirrhosis. The terminology,
      although cumbersome, was intended to differentiate these disorders from alcohol
      related liver disorders, as they are histologically similar. The term was first
      used by Ludwig in 1980, but has received a tremendous amount of attention in the
      past several years as a result of a better understanding of the scope of the
      problem. Although the pathogenesis has not been fully elucidated, there is a
      tremendous amount of research ongoing in this arena, both clinical and basic, to
      determine how the course of the disease can be altered. This text reviews the
      epidemiology of the disease, leading theories of pathogenesis, and treatment
      options.

PMID- 16083335
TI  - Novel therapeutic targets for Huntington's disease.
AB  - Huntington's disease (HD) is a fatal autosomal-dominant disorder involving
      progressive motor, cognitive and psychiatric symptoms. HD is one of a large
      family of neurodegenerative diseases caused by a trinucleotide (CAG) repeat
      mutation, encoding an expanded tract of glutamines in the disease protein. HD was
      one of the first neurological disorders for which accurate transgenic models were
      created, allowing mechanisms of pathogenesis to be explored at molecular,
      cellular and behavioural levels. In the last decade, the understanding of
      molecular and cellular changes which occur in HD prior to onset of symptoms, and
      at early and late stages of disease progression, has been greatly expanded. A
      wide range of potential molecular targets for therapeutic intervention have been
      identified, associated with a variety of cellular processes including gene
      transcription, protein trafficking, protein degradation, protein-protein
      interactions, glutamatergic synaptic transmission, presynaptic signalling,
      postsynaptic signalling, synaptic plasticity, dopaminergic and neurotrophic
      modulation of synaptic function, experience-dependent neurogenesis, mitochondrial
      function and oxidative metabolism. Presymptomatic testing for the HD gene
      mutation necessitates future development of novel therapeutics aimed at delaying
      onset of symptoms, as well as slowing or reversing disease progression.

PMID- 16083336
TI  - The corticotropin-releasing factor receptor: a novel target for the treatment of
      depression and anxiety-related disorders.
AB  - The treatment of mood disorders has been the subject of intense study for more
      than half a century and has resulted in the discovery and availability of a
      number of compounds that have seen tremendous success in the management of major
      depression and anxiety-related disorders. In spite of this success, these drugs
      have not provided a complete therapeutic solution for all patients and this has
      revitalised the need for a greater understanding of the underlying molecular
      mechanisms and targets involved in these disorders. Elucidation of these novel
      targets will enable the development of a better class of compounds which could
      benefit a greater majority of the patient population and be devoid of the current
      side effect liabilities. Towards that end, this review examines, in detail, the
      prospect of one such target, the corticotropin-releasing factor system, as having
      an enhanced therapeutic profile with the potential of a broader range of efficacy
      with reduced side effect liabilities.

PMID- 16083337
TI  - New targets for neuropathic pain therapeutics.
AB  - Neuropathic pain (NeP) is initiated by a lesion or dysfunction in the nervous
      system. Unlike physiological pain it serves no useful purpose and is usually
      sustained and chronic. NeP encompasses a wide range of pain syndromes of diverse
      aetiologies which together account for > 12 million sufferers in the US.
      Currently, there are a number of therapies available for NeP, including
      gabapentin, pregabalin, anticonvulsants (tiagabine HCl), tricyclic
      antidepressants (amitriptyline, nortriptyline) and acetaminophen/opioid
      combination products (Vicodin, Tylenol #3). However, these products do not
      provide sufficient pain relief and a significant proportion of sufferers are
      refractory (60%). Therefore, there is a need for new therapies that provide more
      predictable efficacy in all patients with improved tolerability. Over the last
      decade, understanding of the basic mechanisms contributing to the generation of
      NeP in preclinical animal models has greatly improved. Together with the
      completion of the various genome sequencing projects and significant advances in
      microarray and target validation strategies, new therapeutic approaches are being
      rigourously pursued. This article reviews the rationale behind a number of these
      mechanism-based approaches, briefly discusses specific challenges that they face,
      and finally, speculates on the potential of emerging technologies as alternative
      therapeutic strategies to the traditional 'small-molecule' approach.

PMID- 16083338
TI  - The ERK/MAPK pathway, as a target for the treatment of neuropathic pain.
AB  - Peripheral nerve injury produces neuropathic pain as well as phosphorylation of
      mitogen activated protein kinase (MAPK) family in dorsal root ganglia (DRG) and
      dorsal horn. Following nerve injury, phosphorylation of extracellular signal
      regulated protein kinase (ERK), an important member of this family, is
      sequentially increased in neurons, microglia and astrocytes of the dorsal horn
      and gracile nucleus, and in injured large DRG neurons. Nerve injury-induced
      phosphorylation of ERK occurs early and is long-lasting. In several animal models
      of neuropathic pain, MEK inhibitors, known to suppress the synthesis of ERK, have
      proven effective to alleviate pain at various time points. Thus, the regulation
      of ERK/MAPK can be considered as a promising therapeutic target for the treatment
      of neuropathic pain.

PMID- 16083339
TI  - Rho kinase as potential therapeutic target for cardiovascular diseases:
      opportunities and challenges.
AB  - Rho kinase (ROCK) belongs to a family of Ser/Thr protein kinases that are
      activated via interaction with the small GTP-binding protein RhoA. Growing
      evidence suggests that RhoA and ROCK participate in a variety of important
      physiological functions in vasculature including smooth muscle contraction, cell
      proliferation, cell adhesion and migration, and many aspects of inflammatory
      responses. As these processes mediate the onset and progression of cardiovascular
      disease, modulation of the Rho/ROCK signalling pathway is a potential strategy
      for targeting an array of cardiovascular indications. Two widely employed ROCK
      inhibitors, fasudil and Y-27632, have provided preliminary but compelling
      evidence supporting the potential cardiovascular benefits of ROCK inhibition in
      preclinical animal disease models and in the clinic. This review summarises the
      molecular biology of ROCK and its biological functions in smooth muscle,
      endothelium and other vascular tissues. In addition, there will be a focus on
      recent progress demonstrating the benefits of ROCK inhibition in several animal
      models of cardiovascular diseases. Finally, recent progress in the identification
      of novel ROCK inhibitors and challenges associated with their development for
      clinical use will be discussed.

PMID- 16083340
TI  - Interleukin-6 and new strategies for the treatment of cancer, hyperproliferative
      diseases and paraneoplastic syndromes.
AB  - Interleukin-6 (IL-6) is a pleiomorphic cytokine whose growth factor properties
      play an important role in the development and progression of many types of
      cancer. IL-6 is produced in response to a variety of stimuli, and is required for
      the development of T and B lymphocytes to effector cells. In certain neoplasias,
      such as multiple myeloma, IL-6 is both produced and required for survival by the
      cancer cell itself. In other neoplasias, IL-6 may come from tissue surrounding
      the tumour. Thus, therapeutic strategies aimed at inhibiting the production,
      expression or action of IL-6 would be quite beneficial in the treatment of
      cancer. Moreover, IL-6 is a pathophysiological factor in several
      hyperproliferative diseases and the paraneoplastic syndromes that often accompany
      cancer, such as cachexia and osteoporosis; thus, anti-IL-6 therapy would be
      useful in treating these entities as well. This expert opinion acquaints the
      reader with IL-6, its physiological responses, the cancer types with which it is
      associated, and discusses the current state of therapy aimed at inhibiting it.

PMID- 16083341
TI  - The insulin-like growth factor-I receptor as a target for cancer therapy.
AB  - This review examines the rationale for targeting the insulin-like growth factor
      (IGF)-I receptor in the therapy of human tumours and their metastases. The
      rationale is based on two crucial findings: 1) in experimental animals, normal
      cells are only partially affected by the deletion of the IGF-I receptor, whereas
      tumour cells undergo apoptosis when the IGF-I receptor is downregulated; and 2)
      cells with a deleted IGF-I receptor are refractory to transformation by viral and
      cellular oncogenes. This review focuses on the mechanisms underlying the
      experimental findings, and discusses the possibility of extrapolating the results
      obtained in animals to the cure of human tumours.

PMID- 16083342
TI  - The phosphoinositide 3-kinase signalling pathway as a therapeutic target in
      squamous cell carcinoma of the head and neck.
AB  - Squamous cell carcinoma of the head and neck (SCCHN) is associated with high
      morbidity and mortality. Despite significant surgical advances and refinement in
      the delivery of chemotherapy and radiotherapy, prognosis has improved little in
      recent decades. Better local control has led to the late presentation of distant
      metastases and novel therapeutic agents are urgently required to prevent relapse,
      control disseminated disease and thus improve survival. PIK3CA encodes the
      p110alpha isoform of phosphoinositide 3-kinase (PI3-K) and is important in SCCHN,
      aberrations in its activity occurring early in the oncogenic process. PI3-K
      signalling promotes cell survival, proliferation, invasion and angiogenesis, all
      contributing to tumour progression. Activation of the PI3-K pathway may also
      mediate resistance to chemotherapy, radiotherapy and novel therapeutic agents
      such as epidermal growth factor receptor inhibitors. Elements of this signalling
      matrix, therefore, offer attractive therapeutic targets in SCCHN as inhibition of
      many malignant characteristics, as well as sensitisation to multiple treatment
      modalities, could be anticipated.

PMID- 16083343
TI  - Calcium/calmodulin-dependent protein kinases as potential targets in cancer
      therapy.
AB  - In this review the authors discuss the expression and activation of a family of
      protein kinases known as the calcium/calmodulin-dependent kinases (CaM-kinase)
      and the role that these kinases have in the activation of antiapoptotic
      signalling pathways. In addition, the authors outline a novel mechanism of
      activation of these kinases by oxidative stress. Founded on this novel mechanism
      of activation and the role that these kinases have in activating antiapoptotic
      signalling pathways, the authors propose that the CaM-kinases would make very
      good targets for sensitising cancer cells to certain therapeutic treatments.
      Furthermore, the authors discuss the role that these kinases have in cell
      transformation and in the regulation of the cell cycle. Based on these roles the
      authors suggest that inhibition of the CaM-kinases not only has the potential to
      sensitise cancer cells, but also has the potential to induce cytostasis in these
      cells.

PMID- 16083344
TI  - Histone deacetylase inhibitors: insights into mechanisms of lethality.
AB  - Histone deacetylases (HDACs) have recently emerged as an important target for
      therapeutic intervention in cancer and potentially other human diseases. By
      modulating the acetylation status of histones, histone deacetylase inhibitors
      (HDACIs) alter the transcription of genes involved in cell growth, maturation,
      survival and apoptosis, among other processes. Early clinical results suggest a
      potentially useful role for HDACIs in the treatment of certain forms of lymphoma
      (e.g., cutaneous T cell lymphoma) and acute leukaemia. An unresolved question is
      how HDACIs induce cell death in tumour cells. Recent studies suggest that
      acetylation of nonhistone proteins may play an important role in the biological
      effects of this class of compounds, and may explain lack of correlation between
      histone acetylation and induction of cell death by HDACIs in some circumstances.
      Recently, attention has focussed on the effects of HDACIs on disruption of co
      repressor complexes, induction of oxidative injury, upregulation of the
      expression of death receptors, generation of lipid second messengers such as
      ceramide, interference with the function of chaperone proteins and modulation of
      the activity of NF-kappaB as critical determinants of lethality. Aside from
      providing critical insights into the mechanism of action of HDACIs in neoplastic
      disease, these findings may provide a foundation for the rational development of
      combination studies, involving HDACIs in combination with either conventional
      cytotoxic drugs as well as more novel targeted agents.

PMID- 16083345
TI  - Oncogene-targeted antisense oligonucleotides for the treatment of Ewing sarcoma.
AB  - The genetic hallmark of the Ewing sarcoma family of tumours (ESFT) is the
      presence of the t(11;22)(q24;q12) translocation, present in up to 85% of cases of
      ESFT, which creates the EWS/FLI1 fusion gene and results in the expression of a
      chimeric protein regulating many other genes. The inhibition of this protein by
      antisense strategies has shown its predominant role in the transformed phenotype
      of Ewing cells. In addition, the junction point at the mRNA level offers a target
      for short therapeutic nucleic acids that is present only in the cancer cells and
      not in the normal tissues of a patient. Several teams have, therefore,
      investigated the activity of antisense oligonucleotides and siRNAs targeted
      against the junction point in mRNA; thus, inhibiting EWS/FLI1 synthesis.
      Generally speaking, the molecules induce a cell growth inhibition in culture.
      Apoptosis has also been reported. One laboratory has reported the in vivo tumour
      inhibitory effect of phosphorothioate antisense oligonucleotide directed against
      the EWS part of EWS/FlI1 when injected intratumourally. Independently, a tumour
      inhibitory effect of oligonucleotides targeting the junction point has been
      demonstrated provided they are delivered by polymeric nanoparticles through the
      intratumoural route. Alongside this target, other genes participating to the
      maintenance of the transformed phenotype of Ewing cells have been downregulated
      by antisense strategies.

PMID- 16083346
TI  - Indoleamine 2,3-dioxygenase in cancer: targeting pathological immune tolerance
      with small-molecule inhibitors.
AB  - Indoleamine 2,3-dioxygenase (IDO) is an interferon (IFN)-gamma-inducible,
      extrahepatic enzyme that catalyses the initial and rate-limiting step in the
      degradation of the essential amino acid tryptophan. Elevated tryptophan
      catabolism mediated by IDO is associated with a wide variety of human cancers and
      has historically been thought to be a tumoricidal consequence of IFN-gamma
      exposure. Evidence of a physiological requirement for IDO activity in protecting
      the allogeneic fetus from rejection by the maternal immune system has stimulated
      a radical shift in thinking about the role of IDO in cancer. Evidence now
      suggests that tumours can exploit IDO-mediated peripheral tolerance to promote
      immune escape. This review summarises key studies that implicate IDO as an
      important mediator of peripheral immune tolerance as well as the development of a
      promising new anticancer modality that incorporates the use of IDO inhibitors.
      The second part focuses on the current state of development of IDO inhibitory
      compounds as potential pharmaceutical agents.

PMID- 16083347
TI  - Phosphoproteomics for oncology discovery and treatment.
AB  - Reversible protein phosphorylation is one of the most important forms of cellular
      regulation. For this reason, phosphoproteomic analysis of protein phosphorylation
      in cells is a powerful tool for evaluating the functional status of cells. The
      importance of protein kinase-regulated signal transduction pathways in human
      cancer has led to the development of drugs that inhibit protein kinases at the
      apex or intermediary levels of these pathways. Phosphoproteomic analysis of these
      signalling pathways will provide important insights into the operation and
      connectivity of these pathways that will facilitate the identification of the
      best targets for cancer therapies. Moreover, phosphoproteomic analysis of
      individual tumours will help match targeted cancer drugs to the appropriate
      patients.

PMID- 16083348
TI  - Peroxisome proliferator-activated receptor beta/delta as a therapeutic target for
      metabolic diseases.
AB  - The peroxisome proliferator-activated receptor (PPAR) family comprises three
      distinct isotypes: PPARalpha, PPARbeta/delta and PPARgamma. PPARs are nuclear
      hormone receptors that mediate the effects of fatty acids and their derivatives
      at the transcriptional level. Until recently, the characterisation of the
      important role of PPARalpha in fatty acid oxidation and of PPARgamma in lipid
      storage contrasted with the sparse information concerning PPARbeta/delta.
      However, evidence is now emerging for a role of PPARbeta/delta in tissue repair
      and energy homeostasis. Experiments with tissue-specific overexpression of
      PPARbeta/delta or treatment of mice with selective PPARbeta/delta agonists
      demonstrated that activation of PPARbeta/delta in vivo increases lipid catabolism
      in skeletal muscle, heart and adipose tissue and improves the serum lipid profile
      and insulin sensitivity in several animal models. PPARbeta/delta activation also
      prevents the development of obesity and improves cholesterol homeostasis in
      obesity-prone mouse models. These new insights into PPARbeta/delta functions
      suggest that targeting PPARbeta/delta may be helpful for treating disorders
      associated with the metabolic syndrome. Although these perspectives are
      promising, several independent and contradictory reports raise concerns about the
      safety of PPARbeta/delta ligands with respect to tumourigenic activity in the
      gut. Thus, it appears that further exploration of PPARbeta/delta functions is
      necessary to better define its potential as a therapeutic target.

PMID- 16083349
TI  - Neuromedin U--a new target in obesity.
AB  - With the increasing prevalence of obesity, effective therapies are urgently
      required. When neuromedin U was administered intracerebroventricularly to rats
      there was a marked decrease in weight, whereas injection of an antibody to
      neuromedin U increased food intake. Unlike wild type, Nmu(-/-) mice become obese
      when freely fed ordinary mouse chow. The plasma levels of insulin, leptin, total
      cholesterol, triglycerides and free fatty acids were higher in the Nmu(-/-) than
      wild-type mice. Energy expenditure was lower in Nmu(-/-) mice. The anorexigenic
      effect of neuromedin U was independent of the leptin signalling pathway.
      Transgenic mice overexpressing neuromedin U have lower body weight, less somatic
      and liver fat, were hypophagic, and had improved insulin sensitivity. These data
      establish neuromedin U as a target in obesity.

PMID- 16083352
TI  - Deformation of the human brain induced by mild acceleration.
AB  - Rapid deformation of brain matter caused by skull acceleration is most likely the
      cause of concussion, as well as more severe traumatic brain injury (TBI). The
      inability to measure deformation directly has led to disagreement and confusion
      about the biomechanics of concussion and TBI. In the present study, brain
      deformation in human volunteers was measured directly during mild, but rapid,
      deceleration of the head (20-30 m/sec2 peak, approximately 40 msec duration),
      using an imaging technique originally developed to measure cardiac deformation.
      Magnetic resonance image sequences with imposed "tag" lines were obtained at high
      frame rates by repeating the deceleration and acquiring a subset of image data
      each repetition. Displacements of points on tag lines were used to estimate the
      Lagrangian strain tensor field. Qualitative (visual) and quantitative (strain)
      results illustrate clearly the deformation of brain matter due to occipital
      deceleration. Strains of 0.02-0.05 were typical during these events (0.05 strain
      corresponds roughly to a 5% change in the dimension of a local tissue element).
      Notably, compression in frontal regions and stretching in posterior regions were
      observed. The motion of the brain appears constrained by structures at the
      frontal base of the skull; it must pull away from such constraints before it can
      compress against the occipital bone. This mechanism is consistent with
      observations of contrecoup injury in occipital impact.

PMID- 16083353
TI  - Diffusion-weighted imaging of edema following traumatic brain injury in rats:
      effects of secondary hypoxia.
AB  - Hypoxia and edema are frequent and serious complications of traumatic brain
      injury (TBI). Therefore, we examined the effects of hypoxia on edema formation
      after moderate lateral fluid percussion (LFP) injury using NMR diffusion-weighted
      imaging (DWI). Adult Sprague-Dawley rats were separated into four groups: sham
      uninjured (S), hypoxia alone (H), trauma alone (T), and trauma and hypoxia (TH).
      Animals in Groups T and TH received LFP brain injury, with Groups H and TH
      undergoing 30 min of moderately severe hypoxia (FiO2 = 0.11) immediately after
      surgery or TBI (respectively). DWIs were obtained at 2, 4, and 24 h and at 1 week
      post injury, and apparent diffusion coefficient (ADC) maps were constructed.
      Animals in Groups T and TH showed an early decrease (p < 0.001) in ADC values in
      the cortex ipsilateral to TBI 4 hr post injury, followed by elevated ADCs 1 week
      later (p < 0.05). No significant differences in ADC values were seen between T
      and TH groups in the ipsilateral cortex. In contrast, the ipsilateral hippocampus
      for Group TH showed only increasing ADC values. This hyperintensity in the ADC
      map began at 2 h after TBI, was significant by 24 h (p < 0.05), and reached a
      maximum at 1 week. This hyperintensity was not observed in Group T.
      Histopathology seen in TBI animals corresponded well with the pathology observed
      with MRI. Midline shifts reflecting edema were only observed in TBI animals with
      little difference between normoxic (T) and hypoxic animals (TH). In sum, this
      study demonstrates that the development and extent of brain edema following TBI
      can be examined in vivo in rats using DWI technology. TBI resulted in an early
      decrease in ADC values indicating cytotoxic edema in the cortex that was followed
      at 1 week by an increase in the ADC that was associated with decreased tissue
      cellularity. Histopathology corresponded well to the regions of brain injury and
      edema visualized by T2 and DWI procedures. Overall, the addition of hypoxia to
      brain injury resulted in a small increase in the magnitude of edema in
      hippocampus and cortex over that seen with trauma alone.

PMID- 16083354
TI  - Slow, medium, or fast re-warming following post-traumatic hypothermia therapy? An
      ultrastructural perspective.
AB  - It was hypothesized that rapid rather than slow re-warming following traumatic
      brain injury (TBI) and short-term hypothermia results in secondary,
      ultrastructural pathology. After stretch injury to the right optic nerve, adult
      guinea pigs were randomly allocated to one of six experimental groups. Either (1)
      sham (all procedures but not stretch-injured; n = 4); injured and (2) maintained
      at normal temporalis core temperature (38.5 degrees C) for 8 hours (n = 6); (3)
      cooled rapidly to 32.5 degrees C (temporalis temperature), maintained for 4 h and
      re-warmed to 38.5 degrees C at 1 degrees C rise every 10 min (fast; n = 6); (4)
      cooled and re-warmed at 1 degrees C rise every 20 min (medium; n = 6); (5) cooled
      and rewarmed at 1 degrees C rise every 40 min (slow; n = 6) before being killed 8
      h after injury; and (6) uninjured animals (n = 6) cooled to 32.5 degrees C for 4
      h and then re-warmed at 1 degrees C every 10 min before killing 4 h later. Tissue
      was processed for light immunocytochemistry (beta-APP and RMO-14) and
      ultrastructural stereology. In both uninjured and injured fast re-warmed animals,
      there was almost total loss of axonal microtubules (MT) and an increased number
      of neurofilaments (NF) within the axoplasm. In the former, there was also
      compaction of NF. The number of MT was reduced to 40% of control values, NFs were
      increased but were not compacted after medium rate re-warming. Following slow re
      warming the axonal cytoskeleton did not differ from that in control animals. It
      is concluded that re-warming faster than 1 degrees C every 40 min following mild
      post-traumatic hypothermia induces secondary axonal pathology.

PMID- 16083355
TI  - Effect of interleukin-1 on traumatic brain injury-induced damage to hippocampal
      neurons.
AB  - Interleukin-1 (IL-1) has many roles in the brain in addition to mediating
      inflammatory processes in the glia, and has also been implicated in
      neurodegenerative disease. Traumatic brain injury (TBI) is one of the most
      prevalent causes of morbidity and mortality in young persons. We conducted a
      study to assess the effect of IL-1 on the TBI-induced death of hippocampal
      neurons. After TBI was induced in adult male Sprague-Dawley rats under
      anesthesia, we evaluated neuronal damage score through microscopic examination
      and Pulsinelli's grading system. Reverse transcription-polymerase chain reaction
      (RT-PCR) and Western blotting were used to measure the levels of IL-1alpha and IL
      1beta in brain tissue at different points after the induction of TBI. Over a 4
      day period, the specific sites of release of IL-1alpha and IL-1beta in the brain
      were elucidated by immunocytochemistry with double- labeling. TBI to the
      hippocampus was followed by disruption of the blood-brain barrier and severe
      neuronal loss. Levels of IL-1alpha RNA and protein were significantly elevated at
      3 h after TBI, peaked at 12 h, and remained elevated for 168 h. IL-1beta RNA and
      protein expression were also elevated at 3 h after TBI, but remained so only for
      48 h. Our findings indicate that the observed TBI-induced increases in IL-1alpha
      and IL-1beta occur largely through release of these cytokines from neurons and
      astrocytes, respectively. Intraventricular administration of antibodies to IL
      1alpha and IL-1beta before TBI significantly attenuated the TBI-induced loss of
      hippocampal neurons. These results show that IL-1alpha and IL-1beta play
      important roles in the TBI-induced loss of hippocampal neurons.

PMID- 16083356
TI  - Cell adhesion molecule l1-transfected embryonic stem cells with enhanced survival
      support regrowth of corticospinal tract axons in mice after spinal cord injury.
AB  - Previous studies have indicated that the cell adhesion molecule L1 enhances
      neuronal survival and neurite outgrowth. L1-mediated promotion of neurite
      outgrowth has been shown to occur also in an inhibitory environment not only in
      vitro, but also in vivo. To further investigate the effects of L1 in spinal cord
      injury, we transfected embryonic stem cells with a plasmid encoding the full
      length mouse L1 molecule under the control of PGK promoter. An embryonic stem
      cell line derived from C57BL/6J transgenic mice that express green fluorescent
      protein under control of the beta-actin promoter was transfected with L1 and
      injected into the lesion site of 3-month-old C57BL/6J female mice 7 days after
      compression injury. Non-transfected embryonic stem cells were detectable at the
      lesion site 3 days after transplantation, but lost their cellular integrity 7
      days after transplantation and were barely detectable 1 month after
      transplantation. In contrast, L1-transfected embryonic stem cells were detected 1
      month after transplantation in numbers comparable to those of the injected cells
      and demonstrated extended processes. Further, in contrast to the few detectable
      nontransfected stem cells that remained at the injection site 1 month post
      transplantation, the L1-transfected embryonic stem cells had migrated rostrally
      and caudally from the lesion. Anterogradely labeled corticospinal tract axons
      showed interdigitation with L1-transfected embryonic stem cells and, in contrast
      to non-transfected stem cells, extended into the lesion site 1 month after
      transplantation and, in some cases, extended beyond it. Our observations
      encourage the use of L1-transfected embryonic stem cells that express L1 not only
      at the cell surface, but also as a soluble and secreted form. Their use could
      condition the inhibitory environment for homophilic L1-enhanced axon regrowth not
      only in spinal cord regeneration, but also in other lesion paradigms.

PMID- 16083357
TI  - In vivo fluorescence tracking of bone marrow stromal cells transplanted into a
      pneumatic injury model of rat spinal cord.
AB  - Recent experimental studies have shown that bone marrow stromal cells (BMSC)
      differentiate into neural cells and reduce neurological deficits when
      transplanted into traumatized spinal cord. These findings have been derived
      primarily from histological analyses. We conducted a study directed chiefly at
      developing a non-invasive system for tracking BMSC transplanted into the spinal
      cord of living animals. In this study, we induced spinal cord injury (SCI) in
      rats with a pneumatic device. BMSC were harvested from transgenic mice expressing
      green fluorescence protein (BMSC-GFP), and were transplanted stereotactically
      into a control group of rats without SCI (n = 6) and a group with SCI (n = 3). At
      2 and 4 weeks after transplantation, the dura mater was exposed and green
      fluorescence derived from the transplanted BMSC-GFP was observed. The
      distribution and differentiation of the transplanted cells were subsequently
      evaluated with immunohistochemistry. Green fluorescence could be detected around
      the transplantation site in three of six of the control rats. In all three rats
      subjected to SCI, green fluorescence was shown to spread from the site of BMSC
      GFP injection toward the injury site, suggesting that the transplanted cells had
      migrated toward the lesion within the 4-week post-transplantation period.
      Histological evaluation suggested that the detected green fluorescence was
      emitted by cells that had distributed in the dorsal white matter, and
      demonstrated that some of the transplanted cells expressed neuronal or astrocytic
      markers. These results suggest the possibility of tracking BMSC transplanted into
      the spinal cord in living animals. Such noninvasive bioimaging techniques would
      be valuable for monitoring the fate of these transplanted cells and assessing the
      safety and efficacy of their transplantation.

PMID- 16083358
TI  - Shedding of tumor necrosis factor type 1 receptor after experimental spinal cord
      injury.
AB  - In a number of stress conditions, the biological effects of tumor necrosis factor
      alpha (TNF-alpha), such as the induction of neuronal apoptosis, are presumably
      attenuated by the soluble fragments of TNF receptors (sTNFRs). Within 1 h after
      spinal cord injury, increased synthesis and/or secretion of TNF-alpha is
      detectable at the injury site. However, the shedding of ectodomains of TNFRs in
      the traumatized spinal cord has not yet been reported. In the present study,
      adult Sprague-Dawley rats were subjected to acute spinal cord injury (ASCI) by
      applying a 25-g Walsh-Tator aneurysm clip at the C8-T1 level. Sham-injured
      animals underwent laminectomy and facetectomy only. A PE10 catheter was placed in
      the subarachnoid space to collect the samples of cerebrospinal fluid (CSF) from
      near the injury site. These CSF samples were analyzed by ELISA for the presence
      of TNF-alpha and soluble TNFR1 and TNFR2 (sTNFR1 and sTNFR2, respectively). The
      spinal cord tissue was analyzed by immunohistochemistry for the expression of TNF
      alpha, TNFR1, and TNFR2, and by the TUNEL technique for the occurrence of
      neuronal death. The levels of TNFR1 and sTNFR1 in the injured tissue were
      determined by Western blotting. Immunohistochemistry demonstrated the increased
      neuronal expression of TNF-alpha and its receptors at 6 h post-ASCI. No changes
      in the intensity of staining were observed in the sham-injured rats. In addition,
      at 6 h after the injury, a significant increase in the number of TUNEL-positive
      neurons was observed. Numerous neurons in traumatized tissue were also
      immunoreactive for activated caspase-3, suggesting that the TUNEL-positive
      neurons were undergoing an apoptotic death. At 1 h after ASCI, TNF-alpha levels
      in the CSF were significantly higher than those found in the sham-injured
      animals, indicating the release of this cytokine into the interstitial fluid.
      This was followed by a significant increase, compared to the sham-injured
      controls, in sTNFR1 levels in the CSF at 3 and 6 h after the insult. Unlike
      sTNFR1, the levels of sTNFR2 in the CSF were unchanged at any time point post
      ASCI. The increased shedding of TNFR1 was confirmed by Western blotting. It is
      concluded that the shedding of TNFR1 receptor may represent an important post
      traumatic physiological response aimed at reducing the proapoptotic effect of TNF
      alpha.

PMID- 16083359
TI  - Upregulation of EphA3 receptor after spinal cord injury.
AB  - Spinal cord injury (SCI) releases a cascade of events that leads to the onset of
      an inhibitory milieu for axonal regeneration. Some of these changes result from
      the presence of repulsive factors that may restrict axonal outgrowth after
      trauma. The Eph receptor tyrosine kinase (RTK) family has emerged as a key
      repellent cue known to be involved in neurite outgrowth, synapse formation, and
      axonal pathfinding during development. Given the nonpermissive environment for
      axonal regeneration after SCI, we questioned whether re-expression of one of
      these molecules occurs during regenerative failure. We examined the expression
      profile of EphA3 at the mRNA and protein levels after SCI, using the NYU
      contusion model. There is a differential distribution of this molecule in the
      adult spinal cord and EphA3 showed an increase in expression after several injury
      models like optic nerve and brain injury. Standardized semi-quantitative RT-PCR
      analysis demonstrated a time-dependent change in EphA3 mRNA levels, without
      alterations in beta-actin levels. The basal level of EphA3 mRNA in the adult
      spinal cord is low and its expression was induced 2 days after trauma (the
      earliest time point analyzed) and this upregulation persisted for 28 days post
      injury (the latest time point examined). These results were corroborated at the
      protein level by immunohistochemical analysis and the cell phenotype identified
      by double labeling studies. In control animals, EphA3 immunoreactivity was
      observed in motor neurons of the ventral horn but not in lesioned animals. In
      addition, GFAP-positive cells were visualized in the ventral region of injured
      white matter. These results suggest that upregulation of EphA3 in reactive
      astrocytes may contribute to the repulsive environment for neurite outgrowth and
      may be involved in the pathophysiology generated after SCI.

PMID- 16083360
TI  - Embodiment in attitudes, social perception, and emotion.
AB  - Findings in the social psychology literatures on attitudes, social perception,
      and emotion demonstrate that social information processing involves embodiment,
      where embodiment refers both to actual bodily states and to simulations of
      experience in the brain's modality-specific systems for perception, action, and
      introspection. We show that embodiment underlies social information processing
      when the perceiver interacts with actual social objects (online cognition) and
      when the perceiver represents social objects in their absence (offline
      cognition). Although many empirical demonstrations of social embodiment exist, no
      particularly compelling account of them has been offered. We propose that
      theories of embodied cognition, such as the Perceptual Symbol Systems (PSS)
      account (Barsalou, 1999), explain and integrate these findings, and that they
      also suggest exciting new directions for research. We compare the PSS account to
      a variety of related proposals and show how it addresses criticisms that have
      previously posed problems for the general embodiment approach.

PMID- 16083361
TI  - An integrated review of indirect, relational, and social aggression.
AB  - Over the last decade, researchers have found that girls may be just as aggressive
      as boys when manipulative forms of aggression, such as gossiping and spreading
      rumors, are included. These forms of aggression are known by 3 different names:
      indirect aggression, relational aggression, and social aggression. This review
      examines their commonalities and differences, and concludes that they are
      essentially the same form of aggression. We show that analogous forms are not
      found in other species. We offer a functional account: indirect aggression is an
      alternative strategy to direct aggression, enacted when the costs of direct
      aggression are high, and whose aim is to socially exclude, or harm the social
      status of, a victim. In this light, we consider sex differences and developmental
      trends and the impact of this aggression on victims. We conclude that indirect,
      relational, and social aggression are much more similar than they are different,
      and we suggest ways in which future research can be facilitated by integrating
      the three areas under an adaptive framework.

PMID- 16083362
TI  - A connectionist model of attitude formation and change.
AB  - This article discusses a recurrent connectionist network, simulating empirical
      phenomena usually explained by current dual-process approaches of attitudes,
      thereby focusing on the processing mechanisms that may underlie both central and
      peripheral routes of persuasion. Major findings in attitude formation and change
      involving both processing modes are reviewed and modeled from a connectionist
      perspective. We use an autoassociative network architecture with a linear
      activation update and the delta learning algorithm for adjusting the connection
      weights. The network is applied to well-known experiments involving deliberative
      attitude formation, as well as the use of heuristics of length, consensus,
      expertise, and mood. All these empirical phenomena are successfully reproduced in
      the simulations. Moreover, the proposed model is shown to be consistent with
      algebraic models of attitude formation (Fishbein & Ajzen, 1975). The discussion
      centers on how the proposed network model may be used to unite and formalize
      current ideas and hypotheses on the processes underlying attitude acquisition and
      how it can be deployed to develop novel hypotheses in the attitude domain.

PMID- 16083364
TI  - For your summertime reading ... and getting primed for cincy.

PMID- 16083365
TI  - The NCI's Clinical Trials Working Group: performing a task worthy of our
      attention.

PMID- 16083366
TI  - Message for mid-term, 2005.

PMID- 16083367
TI  - The National Cancer Institute's Cancer Education (R25E) Grants Program: an
      update.

PMID- 16083368
TI  - Racial disparities in oral cancer risk and outcomes.

PMID- 16083369
TI  - Factors that influence successful training and faculty career development in
      hematology/oncology patient-oriented clinical research.
AB  - BACKGROUND: We wanted to identify what factors promote career development in
      patient-oriented clinical research (POCR). METHODS: We used a survey
      questionnaire covering areas relevant to the training of subspecialty fellows and
      the career development of POCR faculty. RESULTS: Pursuit of an academic career
      after fellowship correlated with completion of a clinical project, availability
      of a clinical research training program, opportunity to earn academic credit,
      faculty mentorship, and obtaining independent career development funding.
      Successful faculty career development in POCR was closely correlated with
      excellent morale and adequate protected time for academic pursuits. CONCLUSIONS:
      Specific academic environmental factors positively influence success in POCR
      hematology/oncology fellowship training and faculty career development.

PMID- 16083370
TI  - A communication intervention for training southern European oncologists to
      recognize psychosocial morbidity in cancer. I--development of the model and
      preliminary results on physicians' satisfaction.
AB  - BACKGROUND: The detection of psychosocial distress is a significant communication
      problem in Southern Europe and other countries. Work in this area is hampered by
      a lack of data. Because not much is known about training aimed at improving the
      recognition of psychosocial disorders in cancer patients, we developed a basic
      course model for medical oncology professionals. METHODS: A specific educational
      and experiential model (12 hours divided into 2 modules) involving formal
      teaching (ie, journal articles, large-group presentations), practice in small
      groups (ie, small-group exercises and role playing), and discussion in large
      groups was developed with the aim of improving the ability of oncologists to
      detect emotional disturbances in cancer patients (ie, depression, anxiety, and
      adjustment disorders). RESULTS: A total of 30 oncologists from 3 Southern
      European countries (Italy, Portugal, and Spain) participated in the workshop. The
      training course was well accepted by most participants who expressed general
      satisfaction and a positive subjective perception of the utility of the course
      for clinical practice. Of the total participants, 28 physicians (93.3%) thought
      that had they been exposed to this material sooner, they would have incorporated
      the techniques received in the workshop into their practices; 2 participants
      stated they would likely have done so. Half of the doctors (n = 15) believed that
      their clinical communication techniques were improved by participating in the
      workshop, and the remaining half thought that their abilities to communicate with
      cancer patients had improved. CONCLUSIONS: This model is a feasible approach for
      oncologists and is easily applicable to various oncology settings. Further
      studies will demonstrate the effectiveness of this method for improving
      oncologists skills in recognizing emotional disorders in their patients with
      cancer.

PMID- 16083371
TI  - Cancer education for Community Health Aides/Practitioners (CHA/Ps) in Alaska
      assessing comfort with cancer.
AB  - BACKGROUND: Village-based Community Health Aides and Community Health
      Practitioners (CHA/Ps) are the primary providers of health care in rural Alaska.
      METHODS: We discuss the development and results of a CHA/P cancer self-assessment
      survey, which assessed comfort with cancer knowledge and providing cancer
      information. RESULTS: A total of 402 responses were received from a mailed
      questionnaire to 477 CHA/Ps. Respondents were predominantly Alaska Native women.
      Using a 5-point Likert scale from don't know to very comfortable, approximately
      50% of CHA/Ps reported feeling "OK" when providing information about cancer risk
      factors, cancer screening, surviving cancer, and providing care and support.
      CHA/Ps reported feeling less comfortable with discussing cancer diagnosis,
      treatment, pain, and loss and grief.

PMID- 16083372
TI  - A survey of attendees at Native American health care conferences: knowledge,
      attitudes, and practices about cigarette smoking.
AB  - BACKGROUND: Cigarette smoking rates and related health consequences among Native
      Americans are the highest of any US ethnic group. METHODS: A sample of the
      attendees at American Indian and Alaska Native health care conferences
      participated in a survey about cigarette smoking. RESULTS: Of 162 respondents,
      11.1% were current smokers, 7.5% of physicians were current smokers, and 80% were
      lifelong nonsmokers. The majority would ask a smoker to put out cigarettes and
      would not display ashtrays at home. Nearly all Native American physicians asked
      their patients about smoking and advised smokers to quit. Respondents were more
      likely to agree that smoking causes lung cancer (98.7%) as compared to knowing of
      the associations of smoking with cervical cancer (70.2%), depression (54.5%), and
      that it is more serious in women (55.2%; P < .01). CONCLUSIONS: Current smoking
      rates were low, and the physicians advised smokers to quit. However, there was
      less awareness about women's health problems that relate to cigarette smoking as
      compared to other health consequences of smoking.

PMID- 16083373
TI  - Prostate cancer knowledge and beliefs among Black and White older men in rural
      and urban counties.
AB  - BACKGROUND: Prostate cancer is the second leading cause of cancer death in men in
      the United States. In this report, we describe prostate cancer knowledge and
      beliefs among subgroups of men and compare knowledge and beliefs with perceived
      personal risk. METHODS: We administered a random-digit-dialed telephone survey to
      235 respondents. RESULTS: Risk factor knowledge was lowest among rural Black men.
      Beliefs across subgroups were more similar than were knowledge levels. Of the
      urban White men, 26% perceived their risk for prostate cancer as high compared to
      10% for other groups. Predictors of low-to-no-or-uncertain self-perceived risk
      included not knowing that age increases risk. CONCLUSIONS: Many Georgia men
      appear to have low levels of knowledge about prostate cancer, especially personal
      risk. Educational and counseling interventions might assist such men in making
      informed screening decisions.

PMID- 16083374
TI  - Cancer prevention among rural youth: building a "bridge" to better health with
      genealogy.
AB  - BACKGROUND: The Bridge to Better Health (BRIDGE) project is a program that
      focuses on providing rural high school youth with motivation, knowledge, and
      skills essential to cancer prevention. In this pilot intervention, we used
      instruction in personal health genealogy as a means of increasing awareness and
      knowledge of health risk and motivation to change several screening and cancer
      related behaviors. METHODS: We administered a Bridge to Better Health survey to
      173 ninth- and 10th-grade students from a rural Southeastern Virginia high school
      before and after delivery of the BRIDGE pilot intervention. RESULTS: Significant
      preintervention to postintervention changes were observed for general genealogy
      knowledge, personal health genealogy, self-efficacy, and intention to practice
      self-examinations (breast, testicular, and skin) and eating a high-fiber and low
      fat diet. CONCLUSION: These project results demonstrate the importance of theory
      driven interventions for increasing cancer knowledge and changing cancer-related
      dietary and screening behaviors.

PMID- 16083375
TI  - Measuring sexual orientation and gender expression among middle-aged and older
      women in a cancer screening study.
AB  - BACKGROUND: The Cancer Screening Project for Women is about the experiences of
      legally unmarried women aged 40 to 75 years. METHODS: Prior to the implementation
      of a survey of experiences with breast, cervical, and colorectal cancer
      screenings, we used cognitive-based interviewing to evaluate questions for
      measuring sexual orientation and gender expression. RESULTS: We conducted
      interviews with 40 women, 19 who partner with women and 21 who partner with men.
      Interviews highlighted respondent confusion, clarified the meaning of terms, and
      improved the comprehension and utility of questions. CONCLUSIONS: Cognitive
      interview techniques can improve the validity and reliability of data collected
      by cancer screening programs.

PMID- 16083376
TI  - Assessing communication between oncology professionals and their patients.
AB  - BACKGROUND: Effective communication with cancer patients continues to be an
      elusive goal for health care professionals (HCPs) and cancer educators. METHODS:
      We posted a survey on the ConversationsInCare.com Web site to collect information
      from oncology HCPs regarding attitudes, effectiveness, and specific patient
      communication skills. RESULTS: The 291 respondents agreed that good communication
      enhances patient satisfaction (76%) and treatment compliance (88%). Only 34% of
      respondents felt comfortable discussing complementary or alternative therapies,
      and approximately half of all respondents felt they lack the skills to help
      patients maintain hope. CONCLUSIONS: Oncology HCPs believe that good
      communication is important and wish to improve their skills. Implications for
      cancer educators are discussed.

PMID- 16083378
TI  - What gives you professional satisfaction?

PMID- 16083377
TI  - Privacy and dignity of cancer patients: a qualitative study of patients privacy
      in UK National Health Service patient care settings.
AB  - BACKGROUND: I undertook this research to determine the extent to which privacy
      and dignity of National Health Service (NHS) patients were respected by health
      practitioners. METHODS: I used the principles of ethnography to undertake
      fieldwork observation of 3 wards within a general hospital to interpret the
      culture of the wards and its impact on the perception and behaviors of patients
      and staff. I used grounded theory and phenomenology to analyze the perceptions
      and experiences. RESULTS: I organized the data into 11 key categories. I adopted
      the classic works of Goffman as interpretative tools, which led to the formation
      of a privacy model. CONCLUSION: Analysis of the categories established that
      patients had very little privacy in acute wards of NHS hospitals.

PMID- 16083380
TI  - A psychologist grows in Brooklyn: reflections from the past.
AB  - In this autobiography, I begin by describing how I made many important decisions
      in my life without much conscious or verbalized thought. I cover information
      about my parents, grandparents, early school experiences, and both college and
      graduate school. The autobiography also includes a detailed discussion of my 41
      years of teaching at the University of Tennessee. I discuss important experiences
      that helped me to become a clinical psychologist and a teacher. I conclude the
      article with a personal experience concerning the death of my mother and an early
      memory.

PMID- 16083381
TI  - Factor analytic models: viewing the structure of an assessment instrument from
      three perspectives.
AB  - The overarching purpose of this article is to present a nonmathematical
      introduction to the application of confirmatory factor analysis (CFA) within the
      framework of structural equation modeling as it applies to psychological
      assessment instruments. In the interest of clarity and ease of understanding, I
      model exploratory factor analysis (EFA) structure in addition to first- and
      second-order CFA structures. All factor analytic structures are based on the same
      measuring instrument, the Beck Depression Inventory-II (BDI-II; Beck, Steer, &
      Brown, 1996). Following a "walk" through the general process of CFA modeling, I
      identify several common misconceptions and improper application practices with
      respect to both EFA and CFA and tender caveats with a view to preventing further
      proliferation of these pervasive practices.

PMID- 16083382
TI  - Reliability and validity of rorschach aggression variables with a sample of
      adjudicated adolescents.
AB  - In this investigation, we assessed the reliability and validity of 5 Rorschach
      aggression variables (AG, A1, A2, AgC, and AgPast) in a sample of adjudicated,
      mostly conduct-disordered adolescents (N = 150). More specifically, we assessed
      the interrelationships of Rorschach aggression variables using correlational
      analyses and factor analysis and assessed the relationships between Rorschach
      variables and a measure of aggressive potential (the Manifest Aggression scale
      from the Jesness Inventory; Jesness, 1996) as well as a measure of real-world
      aggression/violence (the Violence Rating Scale-Revised [VRS-R]; Young, Justice, &
      Erdberg, 1997). Two of Gacono and Meloy's (1994) Rorschach aggression variables
      were dropped from the study (AgPot and SM) due to a low frequency of occurrence.
      All 5 of the remaining Rorschach aggression variables and the VRS-R were rated
      reliably, and factor analysis of the Rorschach variables revealed 2 distinct
      factors accounting for 71% of the total variance. Only the AgC variable
      concurrently predicted aggressive potential and aggressive/violent behavior.
      Results lend further support for the inclusion of AgC in the Comprehensive
      System's (Exner, 1993) list of Special Scores.

PMID- 16083383
TI  - Psychometric properties of the temperament and character inventory-revised (TCI
      R) in a Belgian sample.
AB  - The Temperament and Character Inventory (TCI; Cloninger, Przybeck, Svrakic, &
      Wetzel, 1994) is a self-questionnaire developed to assess the 7 dimensions of
      personality described by Cloninger et al. (1994) with a total of 29 subscales. In
      1999, a revised version was proposed by Cloninger (TCI-R). In this study, we
      present psychometric properties of the TCI-R from 958 French-speaking
      participants of Belgium. Women exhibited higher scores for harm avoidance, reward
      dependence, and cooperativeness dimensions. The proposed factorial structure of 4
      temperament dimensions and 3 character dimensions was confirmed. The TCI-R
      inventory had good test-retest reliabilities as well as good alpha coefficients.
      The addition of 3 new subscales to the original scale for Persistence has
      produced a very reliable dimension in the TCI-R.

PMID- 16083384
TI  - Racial differences in socially desirable responding in selection contexts:
      magnitude and consequences.
AB  - Two studies were conducted to examine the magnitude and consequences of racial
      differences on social desirability (SD) scales. Study 1 included 1,063 job
      applicants, and Study 2 included 3 sets of incumbents (total N = 534). In both
      studies, participants were administered several personality measures and an SD
      scale. Across all samples, Whites scored lower on the SD scale than Blacks
      (average d = .37), Hispanics (average d = .47), and Asians (average d = 1.04),
      but these differences were not observed on the personality scales. The
      consequence of differences in socially desirable responding (SDR) is that fewer
      minority group members would be selected if SD scales were used to derive cut
      scores to eliminate individuals from the applicant pool or if the scales were
      used to correct personality test scores for SDR. However, applying the SD
      correction did not affect the validity of the personality test for any of the
      racial groups. Overall, our findings suggest that researchers and practitioners
      should consider the use of SD scales very carefully, as their use may have
      unintended consequences. These studies also demonstrate a need to closely examine
      the construct validity of SD measures across diverse groups.

PMID- 16083385
TI  - Faking bad and faking good by college students on the Korean MMPI-2.
AB  - Recent studies that have investigated the utility of MMPI-2 (Butcher, Dahlstrom,
      Graham, Tellegen, & Kaemmer, 1989) validity scales have shown the promising
      efficacy of these scales in detecting faking-good and faking-bad responses.
      However, existing research is confined to North America, and work in other
      cultures is still lacking. The purpose of this study lies in exploring the
      efficacy of MMPI-2 validity scales in South Korea. The F, Fb, F - K, and F(p)
      scales of the Korean MMPI-2 (Han, 1993) were able successfully to classify faking
      bad participants. The L, K, and S scales of the Korean MMPI-2 were able
      successfully to classify faking-good participants. Overall, the results of this
      study suggest that the Korean MMPI-2 works well in discriminating dishonest
      responses, thus confirming the applicability of the MMPI-2 validity scales in a
      Korean context.

PMID- 16083386
TI  - Psychometric properties of the Hong psychological reactance scale.
AB  - The Hong Psychological Reactance Scale (HPRS; Hong & Felda, 1996) was developed
      to measure the individual difference in reactance proneness, that is, a person's
      trait propensity to experience psychological reactance. We performed confirmatory
      factor analyses to test the dimensionality of the 11-item version of the HPRS.
      Three message outcome variables (i.e., perceived threat to freedom, attitude, and
      intention) served as reference variables to test the construct validity of the
      HPRS. Data from 3 studies (Ns = 188, 200, and 233) of reactions to persuasive
      health messages confirmed the existence of 4 first-order factors but also
      provided evidence that the HPRS can be treated as unidimensional at the second
      order. The relationships between the second-order factor and the message outcome
      variables provided evidence of the validity of the scale.

PMID- 16083387
TI  - Exploring the hand test with medically ill children and adolescents.
AB  - Pediatric psychologists use the tools of assessment to evaluate the psychological
      functioning of youth with chronic and acute medical illnesses. This study is an
      exploration of the use of a performance-based measure, the Hand Test (HT; Wagner,
      1983), with pediatric medical patients. A sample of medical inpatients (n = 27)
      and psychiatric outpatients (n = 24) were administered the HT, a self-report
      measure, and a parent-report behavior rating scale. Results indicate that the
      psychiatric group scored higher than the medical group on HT Aggression,
      Withdrawal, and Pathological scores. The Aggression (d = 0.90) and Pathological
      (d = 0.80) variables were particularly robust in differentiating between groups,
      but the Crippled variable did not differ between groups. Hierarchical logistic
      regression demonstrated the incremental validity of the HT over behavior ratings
      alone in the classification of clinical groups. Analyses indicated that the HT
      can add important information in the differentiation of medically ill children
      from those with psychological disturbance.

PMID- 16083388
TI  - The illusion of mental health: in the mind of which beholder?
AB  - We reference self-ratings and clinician ratings of childhood anxious symptoms to
      a third data source well delineated with regard to the pathophysiology of
      anxiety. A total of 36 children with anxiety disorders and other children were
      administered yohimbine, an alpha-sub-2-adrenoreceptor antagonist, in response to
      which anxiety-prone children have blunted output of growth hormone. We assessed
      neuroendocrine reactions. In general, participants who claimed anxiety that was
      unconfirmed by clinicians displayed anxiotypic neuroendocrine profiles, whereas
      those who denied anxiety detected by clinicians did not, suggesting self-report
      may have had the advantage over clinician ratings in some instances. Nuanced and
      contextualized conclusions in this area of work are needed. In response to the
      question "the illusion of mental health: in the mind of which beholder?," we
      answer "it depends on the sample and the syndrome under study."

PMID- 16083392
TI  - Evidence-based assessment of learning disabilities in children and adolescents.
AB  - The reliability and validity of 4 approaches to the assessment of children and
      adolescents with learning disabilities (LD) are reviewed, including models based
      on (a) aptitude-achievement discrepancies, (b) low achievement, (c) intra
      individual differences, and (d) response to intervention (RTI). We identify
      serious psychometric problems that affect the reliability of models based on
      aptitude-achievement discrepancies and low achievement. There are also
      significant validity problems for models based on aptitude-achievement
      discrepancies and intra-individual differences. Models that incorporate RTI have
      considerable potential for addressing both the reliability and validity issues
      but cannot represent the sole criterion for LD identification. We suggest that
      models incorporating both low achievement and RTI concepts have the strongest
      evidence base and the most direct relation to treatment. The assessment of
      children for LD must reflect a stronger underlying classification that takes into
      account relations with other childhood disorders as well as the reliability and
      validity of the underlying classification and resultant assessment and
      identification system. The implications of this type of model for clinical
      assessments of children for whom LD is a concern are discussed.

PMID- 16083395
TI  - Clinical utility of EEG in attention deficit hyperactivity disorder.
AB  - Electrophysiological measures were among the first to be used to study brain
      processes in children with attention deficit hyperactivity disorder (ADHD;
      Diagnostic and Statistical Manual of Mental Disorders [4th ed.], American
      Psychiatric Association, 1994) and have been used as such for over 30 years (see
      Hastings & Barkley, 1978, for an early review). More recently,
      electroencephalography (EEG) has been used both in research to describe and
      quantify the underlying neurophysiology of ADHD, but also clinically in the
      assessment, diagnosis, and treatment of ADHD. This review will first provide a
      brief overview of EEG and then present some of the research findings of EEG
      correlates in ADHD. Then, the utility of EEG in making an ADHD diagnosis and
      predicting stimulant response will be examined. Finally, and more
      controversially, we will review the results of the most recent studies on EEG
      biofeedback (neurofeedback) as a treatment for ADHD and the issues that remain to
      be addressed in the research examining the efficacy this therapeutic approach.

PMID- 16083393
TI  - Evidence-based assessment of autism spectrum disorders in children and
      adolescents.
AB  - This article reviews evidence-based criteria that can guide practitioners in the
      selection, use, and interpretation of assessment tools for autism spectrum
      disorders (ASD). As Mash and Hunsley (2005) discuss in this special section,
      evidence-based assessment tools not only demonstrate adequate psychometric
      qualities, but also have relevance to the delivery of services to individuals
      with the disorder (see also Hayes, Nelson, & Jarrett, 1987). Thus, we use what is
      known about the symptoms, etiologies, developmental course, and outcome of ASD to
      evaluate the utility of particular assessment strategies and instruments for
      diagnosis, treatment planning and monitoring, and evaluation of outcome. The
      article begins with a review of relevant research on ASD. Next we provide an
      overview of the assessment process and some important issues that must be
      considered. We then describe the components of a core (minimum) assessment
      battery, followed by additional domains that might be considered in a more
      comprehensive assessment. Domains covered include core autism symptomatology,
      intelligence, language, adaptive behavior, neuropsychological functions, comorbid
      psychiatric illnesses, and contextual factors (e.g., parent well-being, family
      functioning, quality of life). We end with a discussion of how well the extant
      literature meets criteria for evidence-based assessments.

PMID- 16083396
TI  - Incidence of ADHD in adults with severe mental health problems.
AB  - The purpose of this study was to determine the prevalence rates of attention
      deficit hyperactivity disorder (ADHD) and comorbid disorders in an adult
      inpatient psychiatric setting. Patient charts were reviewed from a state hospital
      in the western United States. Of the 292 persons served in 2002, only 6 received
      a diagnosis of ADHD. Of these patients, 2 received additional diagnoses for Major
      Depression, 1 for General Anxiety and 1 for Bipolar Disorder. Five of the 6 ADHD
      participants had a history of substance abuse and 4 were diagnosed with
      Personality Disorders. None of the 6 diagnosed with ADHD received a diagnosis of
      Learning Disability. A variety of nonstimulant medications were utilized to treat
      these patients. Characteristics of adult psychiatric populations are reviewed.
      Prevalence, comorbidity and implications for future research regarding adult ADHD
      are discussed.

PMID- 16083397
TI  - Assessment of attention deficit hyperactivity disorder (ADHD) using the BASC and
      BRIEF.
AB  - There has been an overwhelming increase in the number of children diagnosed with
      attention deficit hyperactivity disorder (ADHD). School and clinical
      psychologists play an important role in the assessment of a child's emotional and
      behavioral difficulties, including problems with attention. Various assessment
      measures, including behavioral rating forms such as the Behavior Assessment
      System for Children (BASC) and the Behavior Rating Inventory of Executive
      Function (BRIEF), are often used in the assessment of a child's behavior. The
      purpose of this article is to provide more knowledge to psychologists regarding
      the assessment of ADHD in children using the BASC and BRIEF. Results from this
      study indicated that the BASC and BRIEF scales appear to be measuring similar,
      but different, constructs pertaining to behaviors associated with ADHD, as well
      as similar study skills and learning problems. These findings suggest that
      children diagnosed with ADHD are rated lower on adaptive skills when compared to
      children with no diagnosis on the BASC. Use of the BASC and BRIEF in ADHD
      assessment appears promising and may generate additional areas in need of
      intervention.

PMID- 16083398
TI  - Delinquency, hyperactivity, and phonological awareness: a comparison of
      adolescents with ODD and ADHD.
AB  - The incidence of reading disabilities in children with attention deficit
      hyperactivity disorder (ADHD) has been found at a higher proportion than would be
      expected by chance. This study explored the relationship between reading problems
      comprehension and phonological awareness, and externalizing behaviors
      hyperactivity (ADHD), and oppositional defiant disorder (ODD). One hundred boys
      from Central Texas area alternative education schools between the ages of 11 and
      15 were grouped by categories: ADHD-Combined Type (ADHD:C), ODD only, a
      combination of ADHD:C and ODD, and children without either ADHD or ODD. Results
      indicated that there were no significant differences among the four groups in
      terms of reading skills. However, findings suggest a significant negative linear
      relationship between hyperactivity and reading skills. Application of these
      findings is discussed.

PMID- 16083399
TI  - Performance of children diagnosed with ADHD on selected planning and
      reconstitution tests.
AB  - A sample of 177 children between the ages of 8 and 12 years, 93 participants
      diagnosed with attention deficit hyperactivity disorder (ADHD) and 85 control
      participants, were administered selected tasks from the WJ-III Tests of Cognitive
      Abilities, Wechsler Intelligence Scale for Children-III (WISC-III), and WISC-III
      PI that targeted various reconstitution skills such as aspects of planning and
      reasoning. Planning from the WJ-III Cog, Wechsler Mazes from the WISC-III, and
      Elithorn Mazes from the WISC-III PI were used to measure the concept of planning
      Concept Formation and Analysis Synthesis from the WJ-III Cog were chosen to
      represent reconstitution. Results indicated that age and gender were not
      contributory factors to differences on the selected measures. IQ was found to be
      contributory and was used as a covariate in all analyses. The overall results of
      the study indicated a need to further divide the broad category of ADHD into its
      subtypes when analyzing performance on measures of executive functions,
      particularly reconstitution. A large effect size was found for Concept Formation
      and results of this study suggested that the Predominately Inattentive Type and
      Combined Type of ADHD had the most difficulty on this task, as shown by the
      significantly lower scores on the measure when compared to the control group and
      the Predominately Hyperactive-Impulsive Type. The Predominately Inattentive
      Hyperactive Impulsive Type did not have any significant difficulties with any of
      the measures used on this task as evidenced by the small effect sizes. Further
      areas to investigate such as metacognitive strategies, distinct problem solving
      strategies, incorporating feedback, and utilizing response inhibition are
      discussed.

PMID- 16083400
TI  - Teachers' perceptions of the incidence and management of attention-deficit
      hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) continues to be a common
      diagnosis of school children, and according to the Diagnostic and Statistical
      Manual of Mental Disorders (4th ed. [DSM-IV], American Psychiatric Association,
      1994), it affects approximately 3%-5% of the population. Teachers are often the
      primary source of information regarding ADHD diagnoses in school children. A
      previous study by Glass and Wegar (2000) found that teachers were overidentifying
      children with ADHD and that medication was preferred as the primary treatment for
      these students. This study further examined teacher perceptions on the causes,
      incidence, and appropriate treatment methods of ADHD. In addition, this study
      also examined the prevalence of ADHD as determined by ADHD Rating Scale-IV
      (School Version; DuPaul et al., 1998) and examined differential identification
      rates by gender and ethnicity. Results showed that teachers were likely to
      identify children as having ADHD at rates higher than the expected prevalence
      rates specified in DSM-IV. Out of 121 rating scales analyzed, 23.97% of students
      were identified by teachers as meeting criteria for 1 of the 3 types of ADHD.
      Males had significantly higher scores than females and Whites had significantly
      higher scores than Hispanics. Class size was also associated with the likelihood
      that teachers would identify more than 5% of their students as having ADHD.
      Results suggest that, despite increasing evidence of a connection between
      biological factors and ADHD, environmental factors (i.e., class size and culture)
      may still influence teachers' perceptions about what students have the disorder.

PMID- 16083401
TI  - Factors influencing osteoporosis knowledge: a community study.
AB  - According to the 2004 Surgeon General's report, more than 10 million people in
      the United States have osteoporosis, and another 34 million are at risk of
      developing this crippling disease that affects the quality of life. Efforts must
      be made to stem this disease that may be largely prevented with lifestyle
      changes. To engage in self-care to prevent osteoporosis, people need to have
      knowledge of risks and preventive behaviors. The purpose of this study was to
      examine factors influencing osteoporosis knowledge in 255 people in a university
      community. The Facts on Osteoporosis Quiz (Ailinger, Lasus, & Braun, 2003) was
      used to measure osteoporosis knowledge. Findings indicated that respondents had
      inadequate knowledge about osteoporosis. Age was positively correlated with
      knowledge (r = .27, p < .000), but education was not. There were marked
      differences in mean scores among ethnic groups. The findings suggest topics that
      community health nurses need to focus on in their osteoporosis educational
      interventions.

PMID- 16083402
TI  - Adherence with hypertension care among Hmong Americans.
AB  - To assess contexts of adherence with hypertension care among Hmong Americans, in
      person interviews were conducted with a convenience sample of 323 adults using
      culturally adapted survey instruments. The mean age of participants was 58 years;
      91% had no education, and 86% spoke no English. Although more than 90% had health
      insurance and were treated with medications, the rate of blood pressure control
      was low (27%). A majority (> 90%) suffered from psychological distress, and 46%
      lived with physical illness. Over 50% reported nonadherence with hypertension
      care. Respondents who were 50 years of age or older, had no physical illness, did
      not know that hypertension was preventable, or believed that American medicine
      was too strong, were more likely to report nonadherence with proper medication
      consumption. Findings suggest that adherence was not due to lack of health care
      coverage; instead, it may be due to gaps in health services.

PMID- 16083403
TI  - Process evaluation of a nurse-delivered smoking relapse prevention program for
      new mothers.
AB  - The objective of this study(1) is to evaluate the feasibility, recall, and
      acceptability of an evidence-based intervention using home-health nurses to
      provide smoking relapse prevention skills to new mothers. The design of this
      study is process evaluation. Setting and participants include women who had
      delivered a normal newborn at a university hospital, who quit smoking during
      pregnancy, were smoke free for 7 days, and had saliva cotinine of less than or
      equal to 14 nanogram/ml. The intervention is a multicomponent cognitive
      behavioral intervention, including inpatient contact, a home-health visit, and 2
      follow-up phone calls. Results are as follows: 121 participants enrolled, and the
      intervention was implemented in 78 home visits. Nurses discussed tobacco issues
      for an average of 12.0 min. Almost all participants recalled the home visit;
      nearly two thirds recalled discussing tobacco use. Only 4% reported negative
      feelings toward discussing tobacco issues. In 87% of home visits, nurses
      implemented all 5 intervention components with self-reported nonsmokers. The
      conclusion is as follows: A nurse-delivered smoking relapse prevention
      intervention for new mothers was feasible and acceptable.

PMID- 16083404
TI  - Healthy behaviors, self-efficacy, self-care, and basic conditioning factors in
      older adults.
AB  - A secondary statistical analysis of data from a study investigating the relations
      among health-promoting self-care behaviors, self-care self-efficacy, and self
      care agency in an older adult population is reported (Callaghan, in press).
      Influences of selected basic conditioning factors on the practice of healthy
      behaviors, self-efficacy beliefs, and ability for self-care in 235 older adults
      is presented. The research instruments used to collect data for this study
      include the following: Health-Promoting Lifestyle Profile II scale, Self-Rated
      Abilities for Health Practices scale, Exercise of Self-Care Agency scale, and a
      demographic questionnaire assessing basic conditioning factors. Statistically
      significant relations were found between the following basic conditioning factors
      and the study variables: education, income, health insurance, race, support
      system, routine practice of religion, medical problems, marital status, gender,
      age, and number of children. Community health nurses can use these results in
      directing interventions that promote the self-care and health of older adults.

PMID- 16083406
TI  - Theory and practice in health communication campaigns: a critical interrogation.
AB  - In recent reviews of the body of work on health campaigns, communication scholars
      discussed the importance of reflective thinking about the capacity of campaigns
      to effect change; this reflective thinking is especially important in the realm
      of the increasing gaps in society between the health rich and the health poor and
      the increasing marginalization of the poorer sections of society. This article
      critically reviews 3 central theories of health communication campaigns that
      represent the dominant cognitive approach: theory of reasoned action, health
      belief model, and the extended parallel process model. After articulating the
      limitations of these theoretical approaches, the article summarizes new
      directions in theory, methodology, and application of health communication
      campaigns targeting marginalized populations.

PMID- 16083407
TI  - Examining empathy in medical encounters: an observational study using the
      empathic communication coding system.
AB  - Educators, researchers, clinicians, and patients often advocate empathy in the
      physician-patient relationship. However, little research has systematically
      examined how patients present opportunities for physicians to communicate
      empathically and how physicians respond to such opportunities. The Empathic
      Communication Coding System was used to investigate empathic opportunity-response
      sequences during initial visits in a general internal medicine clinic. This study
      focuses on 100 visits during which patients created at least 1 explicit empathic
      opportunity. Overall, patients presented 249 empathic opportunities in these 100
      visits; physicians most often responded by acknowledging, pursuing, or confirming
      the patient's statement. The mean length of empathic opportunity-response
      sequences was 25.8 sec; sequences tended to be longer in duration when the
      physician used a more empathic response. Positively valenced empathic
      opportunities generated a more empathic response than did negatively valenced
      empathic opportunities. However, there was no relation between the emotional
      intensity of empathic opportunities and the level of empathy in subsequent
      physician responses. Further research should examine patient preferences and
      outcomes associated with varying levels of empathic responses.

PMID- 16083408
TI  - Using the theory of planned behavior and a stage model of persuasion to evaluate
      a safety message for firefighters.
AB  - A field study was conducted to evaluate the effectiveness of a National Institute
      for Occupational Safety and Health (NIOSH) health and safety message targeted at
      firefighters and to examine predictors of safety intentions among this group.
      This project examined: (a) the ability of the theory of planned behavior (TPB) to
      predict behavioral intentions for firefighters receiving a NIOSH occupational
      safety and health message; and (b) the use of a persuasion output matrix to
      assess message impact. A message about firefighting safety was nationally
      distributed to 36,000 fire chiefs, from which 781 were randomly selected to
      complete a survey assessing message impact and behavioral intentions. Results
      indicate message impact was weakest at the exposure, recall, and action stages of
      persuasion output. The TPB variables were found to significantly predict safety
      intentions.

PMID- 16083409
TI  - Food, culture, and family: exploring the coordinated management of meaning
      regarding childhood obesity.
AB  - Increased rates of childhood obesity combined with more accessible information
      about the relationship between diet, physical activity and inactivity, and
      chronic diseases suggest the need for analyzing the complex process of receiving
      and transmitting messages related to child feeding practices. This study examined
      the perceptions of childhood obesity within 1 multiethnic community, the
      Commonwealth of the Northern Mariana Islands. In particular, through the use of
      focus groups, individuals indicated that sociocultural, familial, and official
      nutritional messages were most influential to their health care behaviors. The
      coordinated management of meaning (CMM) theory was used to gain insight into how
      individuals negotiate competing messages occurring at different levels of
      meaning. Given its focus on cultural influences (parallel to the concepts of
      archetypes), CMM proved especially relevant for understanding child feeding
      beliefs, values, attitudes, and practices in diverse ethnic populations.
      Implications for future health communication research that might draw from a CMM
      approach were identified, as well as pragmatic endeavors that focus on the
      development, implementation, and evaluation of culturally appropriate
      interventions in the prevention of childhood obesity.

PMID- 16083410
TI  - Tobacco-prevention messages online: social marketing via the Web.
AB  - Antitobacco groups have joined millions of other commercial or noncommercial
      entities in developing a presence on the Web. These groups primarily represent
      the following different sponsorship categories: grassroots, medical, government,
      and corporate. To obtain a better understanding of the strengths and weaknesses
      in the message design of antitobacco Web sites, this project analyzed 100
      antitobacco Web sites ranging across these four sponsorship categories. The
      results show that the tobacco industry sites posted just enough antismoking
      information to appease the antismoking publics. Medical organizations designed
      their Web sites as specialty sites and offered mostly scientific information.
      While the government sites resembled a clearinghouse for antitobacco related
      information, the grassroots sites represented the true advocacy outlets. In
      general, the industry sites provided the weakest persuasive messages and medical
      sites fared only slightly better. Government and grassroots sites rated most
      highly in presenting their antitobacco campaign messages on the Web.

PMID- 16083411
TI  - Bibliography.

PMID- 16083412
TI  - When is artificial light hazardous?

PMID- 16083413
TI  - Is artificial light at night too much of a good thing?

PMID- 16083414
TI  - Retinal damage by optical radiation. An alternative to current, ACGIH-inspired
      guidelines.
AB  - BACKGROUND: The ACGIH guidelines for protection against retinal damage by optical
      radiation are often difficult to apply due to their lack of transparency. The
      less known guidelines by the Netherlands Health Council (HCN), dating from 1978
      and updated in 1993, might offer a way out in many cases. METHODS: A comparison
      is made of these guidelines, embedded in a short sketch of the history. They are
      illustrated by examples of applications. RESULTS: In most cases the HCN
      guidelines produce results that hardly deviate from those obtained with the ACGIH
      guidelines but in some cases the results diverge and in other cases HCN gives an
      answer where ACGIH seems to fall short. CONCLUSIONS: The HCN guidelines form a
      good alternative to those of ACGIH.

PMID- 16083415
TI  - Vision and falls.
AB  - Falls occur in about one third of older people living independently in the
      community every year. This can lead to significant physical, psychological and
      financial costs to the individual and the community. While the risk factors for
      falls in older people are multifactorial, poor vision is considered to be an
      important contributing factor. The aim of this review is to evaluate current
      research linking impaired visual function with falls and to review current
      intervention strategies for the prevention of falls in older individuals. The
      evidence from the current literature indicates that impairment of visual
      functions, such as visual acuity, contrast sensitivity, visual fields and depth
      perception, is associated with an increased risk of falls. Recent studies have
      also demonstrated that falls can be reduced following cataract surgery as a
      visual intervention. Optometrists need to be aware of these associations and
      through appropriate treatment, referral and/or education, they can play a major
      role in optimising visual function in older people, as part of a
      multidisciplinary approach to falls prevention.

PMID- 16083416
TI  - Applications of high-speed videokeratoscopy.
AB  - High-speed videokeratoscopy is an emerging technology that has the potential to
      provide new information on dynamic changes of corneal topography and tear film
      behaviour. We have developed a high-speed videokeratoscope that has the ability
      to acquire data at the rate of 50 Hz. Two major applications of the technology
      are considered in this paper. First, the analysis of tear film stability in the
      inter-blink interval is evaluated and techniques for estimating the tear film
      build-up and break-up times are considered. The second application involves the
      study of the dynamic response of the corneal anterior surface to mechanical
      forces exerted by the eyelids during horizontal eye movements in downward gaze.
      The limitations and potential opportunities for the use of this new technology
      are discussed.

PMID- 16083417
TI  - Incidence and morbidity of hospital-presenting corneal infiltrative events
      associated with contact lens wear.
AB  - AIM: To determine the incidence and morbidity (visual loss) of hospital
      presenting corneal infiltrative events (CIEs) associated with the wearing of
      current generation contact lenses. METHODS: All contact lens wearers presenting
      with any form of corneal infiltrate/ulcer to a hospital centre in Manchester, UK,
      were surveyed in this 12-month, prospective, hospital-based epidemiological
      study. A clinical severity matrix was used to quantify the overall severity of
      presenting signs and symptoms. The size of the hospital catchment population and
      the wearing modalities (daily wear [DW] or extended wear [EW]) and lens types
      used in that population were estimated from relevant demographic and market data
      to facilitate the calculation of incidence. We also attempted to ascertain, from
      their eye care practitioners, the visual acuity (VA) of patients suffering from
      CIEs prior to and at about six months following attendance at the hospital.
      RESULTS: During the survey period, 118 patients presented with CIEs of varying
      severity. The annual incidence (cases per 10,000 wearers) for all wearing
      modalities and lens types is 21.3 (95 per cent confidence interval 17.8 to 25.5).
      The incidence of CIEs for each wearing modality and lens type is: DW rigid, 8.6
      (3.9 to 18.7); DW hydrogel daily disposable, 14.0 (9.3 to 21.0); DW hydrogel
      (excluding daily disposable), 20.4 (15.9 to 26.2); DW silicone hydrogel, 55.9
      (9.9 to 309.6); EW rigid, zero (0.0 to 1758.8); EW hydrogel, 144.6 (66.4 to
      311.8) and EW silicone hydrogel, 118.6 (75.2 to 186.7). The risk of developing a
      CIE with EW lenses was 8.1 (5.3 to 12.5) times greater than that with DW lenses
      (p < 0.0001). Although there was no difference between EW hydrogel and EW
      silicone hydrogel lenses with respect to the risk of developing CIEs, the
      clinical severity of CIEs was greater with EW hydrogel lenses (p = 0.04). Results
      of VA for pre- and post-hospital attendance were obtained from 38 patients, none
      of whom lost more than one line of VA. For the study population, zero patients
      (95 per cent CI: 0 to 9.2 per cent) suffered a significant loss of VA as a result
      of developing a CIE. CONCLUSIONS: Overall, there is an eight times higher
      incidence of CIEs in wearers who sleep in contact lenses compared with wearers
      who use lenses only during the waking hours. For those who choose to routinely or
      intermittently sleep in soft contact lenses, silicone hydrogels are the lens of
      first choice because CIEs are less clinically severe with this lens type compared
      with hydrogel lenses. The rate of significant visual loss as a result of
      developing a CIE is low.

PMID- 16083418
TI  - Diagnosing protan heterozygosity using the Medmont C-100 colour vision test.
AB  - BACKGROUND: A surprisingly high 15 per cent of women in Caucasian societies are
      carriers of the genes for abnormal colour vision but there is no clinical method
      to identify them. It has long been known that heterozygotes for the protan colour
      vision deficiencies can demonstrate a reduced luminous sensitivity to red light.
      This is known as Schmidt's sign, which is thought to arise from mosaicism
      (Lyonisation). The Medmont C-100 colour vision test measures relative spectral
      sensitivity using flicker photometry to differentiate protans and deutans. It
      should be able to diagnose Schmidt's sign. METHOD: We tested six known protan
      heterozygotes (four whose sons have a protan colour vision deficiency and two
      whose fathers are protan) with the Medmont C-100 test. RESULTS: All six
      heterozygotes made average settings of -1.75 or more negative at the Medmont C
      100 test, settings which are at or beyond the boundary of the distribution of
      settings made by observers with normal colour vision. There have been two
      previous cases reported in the literature of protan heterozygotes, who made
      protan settings on the Medmont C-100 or its predecessor test, the OSCAR. We also
      tested six daughters of the known heterozygotes, 50 per cent of whom are likely
      to be heterozygotes. Four of the six (66 per cent) made protan settings on the
      Medmont C-100. The other two made normal 0.0 settings. CONCLUSION: We conclude
      that the Medmont C-100 can be used clinically to diagnose carriers of protan
      colour vision deficiency.

PMID- 16083419
TI  - Central serous chorioretinopathy and bullous retinal detachment: a rare
      association.
AB  - While idiopathic central serous retinopathy (ICSC) is a common ocular condition,
      bullous exudative retinal detachment associated with ICSC is a relatively rare
      finding. Bullous retinal detachment has been described as a severe variant of
      ICSC, characterised by multiple leaking pigment epithelial detachments and the
      presence of shifting neuro-sensory sub-retinal fluid. The peculiar clinical
      findings may present a diagnostic dilemma and lead to inappropriate treatment.
      Here, we describe the atypical presentation of ICSC with bullous retinal
      detachment and the effect of focal laser treatment on resolution of the retinal
      detachment. Despite ICSC being a self-limiting condition in the majority of
      cases, recognition of this atypical form of ICSC is important. Failure to
      differentiate this condition from inflammatory disease of the retina and choroid
      may result in inappropriate use of corticosteroids, leading to exacerbation of
      the condition and permanent visual loss.

PMID- 16083420
TI  - Clinical application of mfERG/VEP in assessing superior altitudinal hemifield
      loss.
AB  - Multifocal ERG (mfERG) and multifocal VEP (mfVEP) have been used widely in the
      investigation of pathological changes or functional variations in the visual
      system. Altitudinal hemifield loss is a visual field defect that is usually found
      in patients with ischaemic optic neuropathy (ION). Anterior ischaemic optic
      neuropathy (AION) is a complex multi-factorial disease and it is difficult to
      diagnose according to clinical symptoms and signs alone. AION is believed to be
      caused by an infarction of the optic nerve due to the occlusion of the posterior
      ciliary arteries. The current report presents a patient diagnosed with non
      arteritic AION. In this report, the mfERG findings did not match the results of
      the visual field test but those of the mfVEP did. After consideration of the
      visual electrophysiological and visual field results, the defect arises from
      neither the retina nor the visual pathway behind the optic chiasma. Hence, the
      optic nerve is the most likely location of the lesion, causing the superior
      altitudinal hemi-field loss. This report shows that the mfERG and mfVEP
      techniques can be used for objective visual field assessment to supplement the
      conventional visual field testing.

PMID- 16083421
TI  - Cobbled tongue.

PMID- 16083422
TI  - The N-terminal 26-residue fragment of human programmed cell death 5 protein can
      form a stable alpha-helix having unique electrostatic potential character.
AB  - PDCD5-(1-26) is a N-terminal 26-residue fragment of human PDCD5 (programmed cell
      death 5) protein. PDCD5 is an important novel protein that regulates both
      apoptotic and non-apoptotic programmed cell death. The conformation of PDCD5
      protein is a stable helical core consisting of a triple-helix bundle and two
      dissociated terminal regions. The N-terminal region is ordered and contains
      abundant secondary structure. Overexpression and purification of the N-terminal
      26-residure fragment, PDCD5-(1-26), was performed in this study to better
      understand its tertiary structure. The spectroscopic studies using CD and hetero-
      and homo-nuclear NMR methods determine a stable alpha-helix formed by Asp3-Ala19
      of PDCD5-(1-26). The N-terminal residues Asp3-Ala19 of PDCD5 were then affirmed
      to have the capacity to form a stable alpha-helix independently of the core of
      the protein. Analysis of the helical peptide of PDCD5-(1-26) indicates that the
      surface of this well-formed alpha-helix has a unique electrostatic potential
      character. This may provide an environment for the N-terminal alpha-helix of
      PDCD5 to serve as an independent functional entity of the protein. The apoptosis
      activity assay shows that the deletion of the N-terminal alpha-helix of PDCD5
      significantly attenuates the apoptosis-promoting effects on HL-60 cells induced
      by serum withdrawal.

PMID- 16083423
TI  - The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension
      syndrome phosphorylate and activate SPAK and OSR1 protein kinases.
AB  - Mutations in the human genes encoding WNK1 [with no K (lysine) protein kinase-1]
      and the related protein kinase WNK4 are the cause of Gordon's hypertension
      syndrome. Little is known about the molecular mechanism by which WNK isoforms
      regulate cellular processes. We immunoprecipitated WNK1 from extracts of rat
      testis and found that it was specifically associated with a protein kinase of the
      STE20 family termed 'STE20/SPS1-related proline/alanine-rich kinase' (SPAK). We
      demonstrated that WNK1 and WNK4 both interacted with SPAK as well as a closely
      related kinase, termed 'oxidative stress response kinase-1' (OSR1). Wildtype (wt)
      but not catalytically inactive WNK1 and WNK4 phosphorylated SPAK and OSR1 to a
      much greater extent than with other substrates utilized previously, such as
      myelin basic protein and claudin-4. Phosphorylation by WNK1 or WNK4 markedly
      increased SPAK and OSR1 activity. Phosphopeptide mapping studies demonstrated
      that WNK1 phosphorylated kinase-inactive SPAK and OSR1 at an equivalent residue
      located within the T-loop of the catalytic domain (Thr233 in SPAK, Thr185 in
      OSR1) and a serine residue located within a C-terminal non-catalytic region
      (Ser373 in SPAK, Ser325 in OSR1). Mutation of Thr185 to alanine prevented the
      activation of OSR1 by WNK1, whereas mutation of Thr185 to glutamic acid (to mimic
      phosphorylation) increased the basal activity of OSR1 over 20-fold and prevented
      further activation by WNK1. Mutation of Ser325 in OSR1 to alanine or glutamic
      acid did not affect the basal activity of OSR1 or its ability to be activated by
      WNK1. These findings suggest that WNK isoforms operate as protein kinases that
      activate SPAK and OSR1 by phosphorylating the T-loops of these enzymes, resulting
      in their activation. Our analysis also describes the first facile assay that can
      be employed to quantitatively assess WNK1 and WNK4 activity.

PMID- 16083424
TI  - Characterization of CA XV, a new GPI-anchored form of carbonic anhydrase.
AB  - The main function of CAs (carbonic anhydrases) is to participate in the
      regulation of acid-base balance. Although 12 active isoenzymes of this family had
      already been described, analyses of genomic databases suggested that there still
      exists another isoenzyme, CA XV. Sequence analyses were performed to identify
      those species that are likely to have an active form of this enzyme. Eight
      species had genomic sequences encoding CA XV, in which all the amino acid
      residues critical for CA activity are present. However, based on the sequence
      data, it was apparent that CA XV has become a non-processed pseudogene in humans
      and chimpanzees. RT-PCR (reverse transcriptase PCR) confirmed that humans do not
      express CA XV. In contrast, RT-PCR and in situ hybridization performed in mice
      showed positive expression in the kidney, brain and testis. A prediction of the
      mouse CA XV structure was performed. Phylogenetic analysis showed that mouse CA
      XV is related to CA IV. Therefore both of these enzymes were expressed in COS-7
      cells and studied in parallel experiments. The results showed that CA XV shares
      several properties with CA IV, i.e. it is a glycosylated
      glycosylphosphatidylinositol-anchored membrane protein, and it binds CA
      inhibitor. The catalytic activity of CA XV is low, and the correct formation of
      disulphide bridges is important for the activity. Both specific and non-specific
      chaperones increase the production of active enzyme. The results suggest that CA
      XV is the first member of the alpha-CA gene family that is expressed in several
      species, but not in humans and chimpanzees.

PMID- 16083426
TI  - Aurora-A site specificity: a study with synthetic peptide substrates.
AB  - AurA (Aurora-A) is a ubiquitous protein kinase regulating entry into mitosis and
      shown to promote transformation upon overexpression. In order to gain information
      on the structural features determining its substrate specificity, we assayed
      human recombinant AurA on a variety of phosphoacceptor peptide substrates
      including a series of properly modified derivatives of the Kemptide (ALRRASLGAA).
      The data presented here show that AurA is a basophilic Ser/Thr protein kinase
      recognizing the consensus R/K/N-R-X-S/T-B, where B denotes any hydrophobic
      residue with the exception of Pro. We show that the presence of a Pro at position
      n+1 fully abrogates phosphorylation of the peptide substrate. Although the
      consensus for AurA is reminiscent of that of PKA (protein kinase A), it
      significantly differs from the latter for a much more stringent dependence on the
      hydrophobic residue at n+1 and for its tolerance of residues other than Arg at
      position n-3. Based on the finding that the peptide ALKRASLGAA is not a substrate
      of PKA while still providing a sensitive assay of AurA activity, we suggest that
      this peptide may be used for differential screening of the two kinases. We have
      further validated the AurA consensus by generating a peptide (APSSRRTT288LCGT)
      that comprises the main AurA autophosphorylation site and by showing that AurA
      phosphorylated this peptide exclusively at one site fulfilling its consensus
      (Thr288). Moreover, we show that AurA could autophosphorylate at Thr288 through
      an intermolecular mechanism of reaction and that, in vivo, PKA was not involved
      with Thr288 phosphorylation. The evidence obtained in the present study provides
      a rational tool for predicting AurA sites in potential substrates of
      physiological significance.

PMID- 16083425
TI  - RhoGDI: multiple functions in the regulation of Rho family GTPase activities.
AB  - RhoGDI (Rho GDP-dissociation inhibitor) was identified as a down-regulator of Rho
      family GTPases typified by its ability to prevent nucleotide exchange and
      membrane association. Structural studies on GTPase-RhoGDI complexes, in
      combination with biochemical and cell biological results, have provided insight
      as to how RhoGDI exerts its effects on nucleotide binding, the membrane
      association-dissociation cycling of the GTPase and how these activities are
      controlled. Despite the initial negative roles attributed to RhoGDI, recent
      evidence has come to suggest that it may also act as a positive regulator
      necessary for the correct targeting and regulation of Rho activities by
      conferring cues for spatial restriction, guidance and availability to effectors.
      These potential functions are discussed in the context of RhoGDI-associated
      multimolecular complexes, the newly emerged shuttling capability and the
      importance of the particular membrane microenvironment that represents the site
      of action for GTPases. All these results point to a wider role for RhoGDI than
      initially perceived, making it a binding partner that can tightly control Rho
      GTPases, but which also allows them to reach their full spectrum of activities.

PMID- 16083427
TI  - Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2
      and SURF1.
AB  - The biogenesis of eukaryotic COX (cytochrome c oxidase) requires several
      accessory proteins in addition to structural subunits and prosthetic groups. We
      have analysed the assembly state of COX and SCO2 protein levels in various
      tissues of six patients with mutations in SCO2 and SURF1. SCO2 is a copper
      binding protein presumably involved in formation of the Cu(A) centre of the COX2
      subunit. The function of SURF1 is unknown. Immunoblot analysis of native gels
      demonstrated that COX holoenzyme is reduced to 10-20% in skeletal muscle and
      brain of SCO2 and SURF1 patients and to 10-30% in heart of SCO2 patients, whereas
      liver of SCO2 patients' contained normal holoenzyme levels. The steady-state
      levels of mutant SCO2 protein ranged from 0 to 20% in different SCO2 patient
      tissues. In addition, eight distinct COX subcomplexes and unassembled subunits
      were found, some of them identical with known assembly intermediates of the human
      enzyme. Heart, brain and skeletal muscle of SCO2 patients contained accumulated
      levels of the COX1.COX4.COX5A subcomplex, three COX1-containing subcomplexes, a
      COX4.COX5A subcomplex and two subcomplexes composed of only COX4 or COX5A. The
      accumulation of COX1.COX4.COX5A subcomplex, along with the virtual absence of
      free COX2, suggests that the lack of the Cu(A) centre may result in decreased
      stability of COX2. The appearance of COX4.COX5A subcomplex indicates that
      association of these nucleus-encoded subunits probably precedes their addition to
      COX1 during the assembly process. Finally, the consequences of SCO2 and SURF1
      mutations suggest the existence of tissue-specific functional differences of
      these proteins that may serve different tissue-specific requirements for the
      regulation of COX biogenesis.

PMID- 16083428
TI  - The American Academy of Nursing's guidelines for healthcare quality and outcomes:
      implications for pediatric nursing practice.

PMID- 16083429
TI  - Nontraditional therapies for PICU.

PMID- 16083430
TI  - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
AB  - PURPOSE: To provide an in-depth exploration of the complex and potentially life
      threatening condition, congenital adrenal hyperplasia (CAH). CONCLUSIONS: CAH
      affects adrenal gland function, resulting in abnormal steroidogenesis caused by a
      deficiency or complete lack of the enzyme 21-hydroxylase (accounting for 90% of
      CAH cases). Clinical manifestations include ambiguous genitalia in female
      newborns and life-threatening salt-wasting crisis in both male and female
      newborns. PRACTICE IMPLICATIONS: Nurses should encourage and assist CAH patients
      and their parents in taking an active role in the management of their condition.
      Each stage of growth and development will bring new challenges and questions for
      patients and their parents.

PMID- 16083431
TI  - Multidimensional assessment using the adolescent pediatric pain tool: a case
      report.
AB  - PURPOSE: Children's and adolescents' pain experiences are complex and
      multidimensional. Therefore, assessing a single dimension of pain intensity is in
      many instances inadequate. The purpose of this case report is to illustrate the
      benefits of using a multidimensional pain tool to assess vaso-occlusive pain in
      children and adolescents with sickle cell disease. CONCLUSIONS: The adolescent
      pediatric pain tool (APPT) provides a valid multidimensional pain assessment that
      facilitates individual pain assessments that optimize children's and adolescents'
      pain relief interventions and outcomes. PRACTICE IMPLICATIONS: The APPT is
      particularly valuable when clinicians encounter children and adolescents
      experiencing complex, difficult to manage pain.

PMID- 16083432
TI  - Testing a model: a developmental perspective of adolescent male sexuality.
AB  - PURPOSE: This study tested a model of adolescent male sexuality and evaluated its
      usefulness for predicting sexual behaviors among a diverse sample. DESIGN AND
      METHODS: Secondary analysis using a national sample was conducted. Sexuality was
      conceptualized as depending on family, peers, and school. Neighborhood was
      hypothesized to influence sexuality indirectly. Sexuality was hypothesized to
      influence sexual behaviors and age at first sex. Structural equation modeling
      techniques were used with ethnic comparisons. RESULTS: Family was the strongest
      predictor of sexuality. Males who were closer to their family were sexually
      conservative; males closer to peers were sexually permissive. Neighborhood's
      influence was moderated through family and school. Ethnic differences were not
      found. PRACTICE IMPLICATIONS: Sexuality assessments and strengthening family
      relationships are essential.

PMID- 16083433
TI  - Bactericidal household products and antibiotic resistance: issues for parents.

PMID- 16083434
TI  - Life care plans provide a pathway to improved outcomes.

PMID- 16083435
TI  - From research idea to research study: the how.

PMID- 16083436
TI  - Motivational interviewing as a strategy to increase families' adherence to
      treatment regimens.

PMID- 16083437
TI  - Synthesis and secondary structure of loop 4 of myelin proteolipid protein: effect
      of a point mutation found in Pelizaeus-Merzbacher disease.
AB  - To study the effects of a point mutation found in Pelizaeus-Merzbacher disease
      (PMD) on the physicochemical and structural properties of the extracellular loop
      4 of the myelin proteolipid protein (PLP), we synthesized the peptide PLP(181
      230)Pro215 and one mutant PLP(181-230)Ser215 with regioselective formation of the
      two disulphide bridges Cys200-Cys219 and Cys183-Cys227. As conventional amino
      acid building blocks failed to give crude peptides of good quality we had to
      optimize the synthesis by introducing pseudoproline dipeptide building blocks
      during the peptide elongation. In peptide Pro215 the first bridge Cys200-Cys219
      was obtained after air oxidation, but in peptide Ser215 because of aggregation,
      dimethyl sulfoxide (DMSO) oxidation had to be used. The second bridge Cys183
      Cys227 was obtained by iodine oxidation of both Cys (acetamidomethyl, Acm)
      protected peptides. The secondary structures of the parent and mutant loops were
      analysed by circular dichroism (CD) in the presence of trifluoroethanol (TFE) and
      sodium dodecyl sulphate (SDS) as a membrane mimetic. Analysis of the spectra
      showed that the content of alpha-helix and beta-sheet varied differently for both
      peptides in TFE and SDS solutions, demonstrating the sensitivity of their
      conformation to the environment and the differences in their secondary structure.
      The ability of both peptides to insert into the SDS micelles was assayed by
      intrinsic tryptophan fluorescence.

PMID- 16083438
TI  - Chemoselective synthesis of peptides containing major advanced glycation end
      products of lysine and arginine.
AB  - Useful methodologies have been developed, enabling the straightforward synthesis
      of peptides containing N(epsilon)-(carboxymethyl)-L-lysine (CML) and N(epsilon)
      (carboxyethyl)-L-lysine (CEL), the major glycation end-products of lysine. These
      lysine derivatives were successfully incorporated into growing peptide chains via
      standard Fmoc/Ot-Bu peptide synthesis procedures. For the synthesis of peptides
      containing major glycation end-products of arginine, synthetic routes have been
      developed enabling the transformation of ornithine residues in peptides into the
      well-known arginine-derived advanced glycation end-products (AGEs) Glarg,
      carboxymethyl-L-arginine (CMA), MG-H1, MG-H2, MG-H3, and carboxyethyl-L-arginine
      (CEA), respectively, by means of special modifying agents. Furthermore, it was
      shown that Glarg-containing peptides become quantitatively hydrolyzed into CMA
      peptides under physiologic conditions. A similar reaction was observed in case of
      a MG-H3-peptide, which turned into a CEA-peptide under these conditions.

PMID- 16083439
TI  - Novel endomorphin-2 analogs with mu-opioid receptor antagonist activity.
AB  - A series of position 4-substituted endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) analogs
      containing 3-(1-naphthyl)-alanine (1-Nal) or 3-(2-naphthyl)-alanine (2-Nal) in L-
      or D-configuration, was synthesized. The opioid activity profiles of these
      peptides were determined in the mu-opioid receptor representative binding assay
      and in the Guinea-Pig Ileum assay/Mouse Vas Deferens assay (GPI/MVD) bioassays in
      vitro, as well as in the mouse hot-plate test of analgesia in vivo. In the
      binding assay the affinity of all new analogs for the mu-opioid receptor was
      reduced compared with endomorphin-2. The two most potent analogs were [D-1
      Nal(4)]- and [D-2-Nal4]endomorphin-2, with IC50 values 14 +/- 1.25 and 19 +/- 2.1
      nM, respectively, compared with 1.9 +/- 0.21 nM for endomorphin-2. In the GPI
      assay these analogs were found to be weak antagonists and they were inactive in
      the MVD assay. The in vitro GPI assay results were in agreement with those
      obtained in the in vivo hot-plate test. Antinociception induced by endomorphin-2
      was reversed by concomitant intracerebroventricula (i.c.v.) administration of [D
      1-Nal4]- and [D-2-Nal4]-endomorphin-2, indicating that these analogs were mu
      opioid antagonists. Their antagonist activity was compared with that of naloxone.
      At a dose 5 microg per animal naloxone almost completely inhibited
      antinociceptive action of endomorphin-2, while [D-1-Nal4]endomorphin-2 in about
      46%.

PMID- 16083440
TI  - [Ala12]MCD peptide: a lead peptide to inhibitors of immunoglobulin E binding to
      mast cell receptors.
AB  - An effort was made to discover mast cell degranulating (MCD) peptide analogs that
      bind with high affinity to mast cell receptors without triggering secretion of
      histamine or other mediators of the allergic reaction initiated by immunoglobulin
      E (IgE) after mast cell activation. Such compounds could serve as inhibitors of
      IgE binding to mast cell receptors. An alanine scan of MCD peptide reported
      previously showed that the analog [Ala12]MCD was 120-fold less potent in
      histamine-releasing activity and fivefold more potent in binding affinity to mast
      cell receptors than the parent MCD peptide. Because this analog showed marginal
      intrinsic activity and good binding affinity it was subsequently tested in the
      present study as an IgE inhibitor. In contrast to MCD peptide, [Ala12]MCD showed
      a 50% inhibition of IgE binding to the Fc epsilon RI alpha mast cell receptor by
      using rat basophilic leukemia (RBL-2H3) mast cells and fluorescence polarization.
      Furthermore, in a beta-hexosaminidase secretory assay, the peptide also showed a
      50% inhibition of the secretion of this enzyme caused by IgE. An attempt was made
      to relate structural changes and biologic differences between the [Ala12]MCD
      analog and the parent MCD peptide. The present results show that [Ala12]MCD may
      provide a base for designing agents to prevent IgE/Fc epsilon RI alpha
      interactions and, consequently, allergic conditions.

PMID- 16083441
TI  - Purification and mass spectroscopic analysis of human CB1 cannabinoid receptor
      functionally expressed using the baculovirus system.
AB  - The cannabinoid receptor 1 (CB1) cannabinoid receptor is an essential component
      of the cannabinergic system. It has been recognized as a therapeutic target for
      treating numerous diseases and is currently receiving considerable attention by
      the pharmaceutical community. Target-based drug design, utilizing three
      dimensional information of receptor structure and ligand-binding motifs, requires
      significant amounts of purified protein. To facilitate the purification of CB1,
      we have expressed the receptor fused to various epitope tags using the
      baculovirus expression system. In addition, expression levels and ligand-binding
      profiles corresponding to the expressed fusion proteins have been compared. C
      terminal histidine (His)-tagged CB1 gave a Bmax higher than most other systems
      previously reported in the literature, and was selected for subsequent metal
      affinity chromatography purification and mass spectroscopic (MS) analysis.
      Moreover, cells expressing C-terminal His-tagged CB1 were shown to inhibit
      forskolin-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in a
      concentration-dependent manner in the presence of CP-55,940, confirming the
      expressed receptor's functional characteristics. A Western blot analysis of the
      purified receptor showed several forms of CB1, the most abundant being a 57 kDa
      monomeric protein. The purified CB1 preparations were subjected to protein
      digestion followed by MS. Fragments corresponding to >70% of the receptor were
      identified by this method, confirming the identity and purity of the expressed
      protein. The work presented here demonstrates that epitope-tagged CB1 can be
      expressed in sufficient amounts and purified to homogeneity for MS analysis.
      Moreover, these results will serve as a basis for future experiments aimed at
      characterizing the ligand-binding domains using covalently reacting receptor
      probes.

PMID- 16083443
TI  - Infectious pancreatic necrosis in Atlantic salmon, Salmo salar L.
AB  - A clinical and histopathological review was carried out of 21 outbreaks of acute
      infectious pancreatic necrosis (IPN) in Scottish Atlantic salmon, Salmo salar L.,
      farms (13 marine and eight fresh water) during 1991-2004. A distinctive syndrome
      was evident in both post-smolts in sea water and fry in fresh water, where liver
      lesions, which had not previously been associated with IPN, became a consistent
      finding in addition to the more typical pancreatic and intestinal changes.
      Initial cases were described in post-smolts in Shetland, but by the end of the
      period of investigation this type of pathology had extended down the West coast
      of Scotland and into Ireland. Limited viral strain analysis suggested that
      similar strains were involved in both fresh water and sea water and that these
      differed from earlier isolates from rainbow trout, Oncorhynchus mykiss (Walbaum).
      In fresh water, recovered fish frequently developed a greatly distended intestine
      associated with accumulation of undigested food. In sea water, after the initial,
      often significant (50% or more), losses, there were many fish which failed to
      grow and became chronically emaciated and prone to sea louse infection. Although
      use of transfer diets containing immune enhancers and the selection of IPN
      resistant broodstock has reduced losses the disease remains a serious cause of
      economic loss.

PMID- 16083444
TI  - Iron acquisition mechanisms of Flavobacterium psychrophilum.
AB  - Forty strains of Flavobacterium psychrophilum were tested for the production of
      siderophores using the universal Chrome Azurol S (CAS) assay. The majority of the
      strains (85%) were CAS positive (CAS+) and some (15%) were CAS negative (CAS-).
      The cryptic plasmid pCP1 was carried by all positive strains and was lacking from
      negative strains. While a weak catechol reaction was detectable in CAS+ culture
      supernatants, the CAS reaction was, to some extent, heat sensitive, questioning
      whether the positive reaction was caused only by siderophores. The ability to
      grow in vitro under iron-restricted conditions did not correlate with the CAS
      reactivity, as growth of both CAS+ and CAS- strains was similarly impaired under
      iron restriction induced by 2,2 dipyridyl. Suppressed growth under these
      conditions was restored by addition of FeCl3, haemoglobin and transferrin for
      both CAS+ and CAS- strains.

PMID- 16083445
TI  - Inhibition of infectious haematopoietic necrosis virus in cell cultures with
      peptide-conjugated morpholino oligomers.
AB  - Delivery of phosphorodiamidate morpholino oligomers (PMO) into fish cells in
      vitro and tissues in vivo was examined. Uptake was evaluated by fluorescence
      microscopy and flow cytometry after treating cultured cells or live rainbow trout
      with 3' fluorescein-tagged PMO. Arginine-rich peptide conjugated to the 5' end of
      the PMO markedly enhanced cellular uptake in culture by 8- to 20-fold compared
      with non-peptide-conjugated PMO as determined by flow cytometry. Enhanced uptake
      of PMO conjugated to peptide was also observed in tissues of fish treated by
      immersion. The efficacy of PMO as inhibitors of infectious haematopoietic
      necrosis virus (IHNV) replication was determined in vitro. Peptide-conjugated
      PMOs targeting sequences within the IHNV genomic RNA (negative polarity) or
      antigenomic RNA (positive polarity) significantly inhibited replication in a dose
      dependent and sequence-specific manner. A PMO complementary to sequence near the
      5' end of IHNV genomic RNA was the most effective, diminishing titre by 97%, as
      measured by plaque assay and Western blot. These data demonstrate that
      replication of a negative-stranded non-segmented RNA virus can be inhibited by
      antisense compounds that target positive polarity viral RNA, or by a compound
      that targets negative polarity viral RNA.

PMID- 16083446
TI  - Virulence factors and pathogenicity of Hafnia alvei for gilthead seabream, Sparus
      aurata L.
AB  - Virulence factors (eae gene, haemolytic capacity, fimbriae, resistance to the
      bactericidal effect of serum, siderophore production) and pathogenicity for
      gilthead seabream, Sparus aurata L., were analysed for 23 Hafnia alvei strains.
      None of the strains used in LD50 studies were lethal for seabream at doses as
      high as >10(8) cfu mL(-1). In chronic challenge studies differences in severity
      of the inflammatory response were observed between strains. On the basis of
      correlation of the inflammatory response to different strains of H. alvei in
      seabream with those virulence factors studied, it was only possible to establish
      a positive correlation between pathogenicity and resistance to the bactericidal
      effect of fish serum. Gilthead seabream is thus a species with considerable
      resistance to experimental infection with H. alvei. The bacterium does, however,
      have the capacity to remain viable in seabream for up to 3 months, without any
      clinical signs. Hafnia alvei is a well-recognized human and animal pathogen.
      Thus, as the pathogen can coexist with aquaculture operations, cultured gilthead
      seabream could represent a risk to human health as a carrier in some
      circumstances.

PMID- 16083447
TI  - Potential use of a Yersinia ruckeri O1 auxotrophic aroA mutant as a live
      attenuated vaccine.
AB  - The aroA gene of Yersinia ruckeri, which encodes 5-enolpyruvylshikimate 3
      phosphate synthase, was insertionally inactivated with a DNA fragment containing
      a kanamycin resistance determinant and reintroduced by allelic exchange into the
      chromosome of Y. ruckeri 21102 O1 by means of the suicide vector pIVET8. The Y.
      ruckeri aroA::Kan(r) mutant was highly attenuated when inoculated
      intraperitoneally into rainbow trout, with a 50% lethal dose of >5 x 10(7) CFU.
      The mutants were not recoverable from the internal organs 48 h post-inoculation
      or later. The vaccination of rainbow trout with the AroA mutant as a live vaccine
      conferred significant protection (relative percentage survival = 90%) against the
      pathogenic wild-type strain of Y. ruckeri.

PMID- 16083449
TI  - Multiplex PCR assay for the detection of pathogenic Aeromonas hydrophila.

PMID- 16083448
TI  - European eels, Anguilla anguilla (L.), infected with Anguillicola crassus exhibit
      a more pronounced stress response to severe hypoxia than uninfected eels.
AB  - The parasite, Anguillicola crassus is a non-native species that infects naive
      European eels, Anguilla anguilla, and causes pathological damage to the
      swimbladder, potentially compromising their ability to cope with hypoxic
      conditions. This study aimed to elucidate whether anguillicolosis exacerbates the
      stress responses to exposure to hypoxic water, conditions that have been
      implicated in mass mortalities of wild infected European eels. Blood parameters
      in infected and uninfected eels were measured during exposure to severe hypoxia
      over an 8-h period. Infected fish showed significantly higher levels of plasma
      cortisol compared with uninfected eels after 4 h of hypoxia. Uninfected fish
      showed an almost twofold increase in plasma glucose after 8-h exposure to hypoxia
      but infected fish showed no significant change, so that the plasma glucose
      concentration was significantly higher in uninfected eels than in infected eels.
      Both groups showed similar elevations in blood haematocrit, suggesting a similar
      catecholamine response in infected and uninfected eels. The lack of a
      hyperglycaemic response in infected eels, despite indirect evidence of a
      catecholamine response to hypoxia, may reflect an increase in glucose turnover.
      The data suggest that anguillicolosis results in a significantly greater
      corticosteroid stress response to hypoxia accompanied by a higher metabolic cost.

PMID- 16083451
TI  - Classification of nocturia in the adult and elderly patient: a review of clinical
      criteria and selected literature.
AB  - Nocturia increases with age and significantly affects quality of life in both men
      and women. Attempts to determine the pathogenesis of nocturia have been based on
      frequency-volume charts, and three types of nocturia have been identified: low
      voided volume (previously termed low bladder capacity), nocturnal polyuria, and
      mixed origin. Validated clinical criteria based on frequency-volume data allow
      the type of nocturia to be specified using two threshold values, i.e. largest
      voided volume/body weight ratio <4 mL/kg for low voided volume; and nocturnal
      urinary output/body weight ratio >10 mL/kg for nocturnal polyuria. The utility of
      these thresholds was validated in a study of elderly patients with two or more
      nocturia episodes/night. Two other studies have improved the understanding of the
      epidemiology of nocturia. The first showed that in men and women, increased
      incidence with age was greater for nocturia than for the six other common lower
      urinary tract symptoms. The second study suggested that prostate changes in men
      (particularly bladder outlet obstruction caused by benign prostatic hyperplasia,
      which has been considered to be a major cause of nocturia) appear to play a
      relatively small role in the development of nocturia; the correlation was based
      on overall symptom score for seven common urological symptoms. Nocturia should
      thus be treated independently of other lower urinary tract symptoms, especially
      in men. The application of valid diagnostic criteria to differentiate the
      underlying cause of nocturia should help lead to more appropriate and effective
      management of this pervasive problem.

PMID- 16083452
TI  - Nocturia in relation to sleep, health, and medical treatment in the elderly.
AB  - Nocturia is a common condition in the elderly that profoundly influences general
      health and quality of life. It appears to predict a higher risk of death. One
      consequence of nocturia is sleep deterioration, with increased daytime sleepiness
      and loss of energy and activity. Accidents, e.g. falls, are increased both at
      night and during the day in elderly persons with nocturia. Nocturia is caused by
      nocturnal polyuria, reduced voided volumes, or a combination of the two.
      Nocturnal polyuria can be caused by numerous diseases, e.g. diabetes insipidus,
      diabetes mellitus, congestive heart failure, and sleep apnoea. A disorder of the
      vasopressin system, with very low or undetectable vasopressin levels at night, is
      manifested as an increased nocturnal urine output, which in the most extreme
      cases reaches 85% of the 24-h diuresis: the prevalence of low or undetectable
      vasopressin levels at night has been estimated to be 3-4% in those aged >or= 65
      years. Treatment of nocturia may include avoiding excessive fluid intake and use
      of diuretic medication in the afternoon rather than the morning, oral
      desmopressin at bedtime in cases of nocturnal polyuria, and antimuscarinic agents
      in the case of overactive bladder or impaired storage capacity of the bladder.

PMID- 16083453
TI  - Role of muscarinic receptor antagonists in urgency and nocturia.
AB  - The overactive bladder (OAB) syndrome is defined as urgency, with or without
      urgency incontinence, usually accompanied by frequency and nocturia. Muscarinic
      receptor antagonists are the most established form of treatment for OAB, but
      until recently their effectiveness was only confirmed for symptoms of
      incontinence and frequency. In recent studies, selected muscarinic antagonists,
      including darifenacin, solifenacin, tolterodine and trospium, significantly
      reduced the number of urgency episodes per day relative to placebo. While some
      data raise the possibility that certain of these agents may be more effective
      than others in this regard, this variability in their effect on urgency needs to
      be confirmed in future studies. Moreover, it remains to be determined whether
      counting the number of urgency episodes or assessing the subjective intensity of
      the sensation of urgency more adequately reflects patient needs and therapeutic
      efficacy. For nocturia, muscarinic receptor antagonists have only inconsistently
      shown statistically greater effects than placebo. This inconsistency may relate
      to the multifactorial nature of nocturia, which even in patients with OAB can
      have many causes, not all of which may respond/be sensitive to muscarinic
      receptor antagonism.

PMID- 16083454
TI  - The faculty of pain medicine, Australian and New Zealand college of anesthetists.

PMID- 16083455
TI  - The clinical art of pain medicine: balancing evidence, experience, ethics, and
      policy.

PMID- 16083456
TI  - Pushing the pain medicine horizon.

PMID- 16083457
TI  - Percutaneous radiofrequency neurotomy for chronic neck pain: outcomes in a series
      of consecutive patients.
AB  - BACKGROUND: Randomized controlled trials in research settings have demonstrated
      the efficacy of percutaneous radiofrequency neurotomy of the medial branches of
      the cervical dorsal rami in the palliation of chronic zygapophysial joint pain, a
      common cause of chronic neck pain, but one that is under-recognized in some
      quarters. AIMS: This study aimed to determine the outcomes of radiofrequency
      neurotomy in usual clinical practice for patients with established cervical
      zygapophysial joint pain. METHODS: The study was conducted in a public hospital,
      incorporating the private practice and public clinic elements of a single
      physician. All patients who underwent radiofrequency neurotomy had a diagnosis of
      cervical zygapophysial joint pain established by controlled cervical medial
      branch blocks. The primary outcome of duration of pain relief was determined for
      all consecutive procedures performed during a two-year period. Data were
      collected by chart review and telephone contact by an independent assessor.
      RESULTS: Forty-seven procedures were performed on 35 patients. Two patients were
      lost to follow-up. Twelve patients had two procedures. Thirty-six of 45
      assessable procedures (80%) achieved significant pain relief. These 36 procedures
      achieved a mean duration of pain relief of 36 weeks, with a median of 35 weeks.
      Repeat procedures usually achieved reproducible pain relief. Most patients had
      significant postprocedural pain for about one week. Only one serious adverse
      event (local superficial infection) was reported. CONCLUSION: Radiofrequency
      neurotomy is an effective palliative treatment for chronic cervical zygapophysial
      joint pain when performed in routine clinical practice.

PMID- 16083458
TI  - A narrative review of intra-articular corticosteroid injections for low back
      pain.
AB  - OBJECTIVE: To summarize and to analyze the available literature on the efficacy
      of intra-articular injections of corticosteroids for low back pain. DESIGN:
      Publications, in English, French, and German, were obtained that reported the
      proportions of patients who obtained complete relief of pain following intra
      articular steroids, and that provided any form of follow-up. These publications
      were analyzed to determine the rationale, indications, and outcomes of the
      treatment. RESULTS: The only rationale for intra-articular steroids appears to be
      the expectation that they should work. The most commonly used indication has been
      back pain, for which no specific diagnosis has been made. When the results of
      observational studies are pooled, they paint a picture of impressive immediate
      responses, but a rapid decay of outcomes by three and six months. Initial
      responses, however, are dissonant with the literature from controlled studies of
      the prevalence of lumbar zygapophysial joint pain. Moreover, controlled trials
      have shown that there is no attributable effect to the injection of steroids.
      CONCLUSION: The apparent efficacy of lumbar intra-articular steroids is no
      greater than that of a sham injection. There is no justification for the
      continued use of this intervention. Better outcomes can be achieved with
      deliberate placebo therapy.

PMID- 16083459
TI  - A narrative review of intra-articular corticosteroid injections for low back
      pain: Nikolai Bogduk.

PMID- 16083460
TI  - Multidisciplinary pain facility treatment outcome for pain-associated fatigue.
AB  - OBJECTIVES: Fatigue is frequently found in chronic pain patients (CPPs) and may
      be etiologically related to the presence of pain. Fishbain et al. have recently
      demonstrated that chronic low back pain (LBP) and chronic neck pain patients are
      more fatigued than controls. The purpose of this study was to determine whether
      chronic LBP- and chronic neck pain-associated fatigue responded to
      multidisciplinary multimodal treatment not specifically targeted to the treatment
      of fatigue. DESIGN: A total of 85 chronic LBP and 33 chronic neck pain patients
      completed the Multidimensional Fatigue Inventory (MFI), Neuropathic Pain Scale
      (NPS), and Beck Depression Inventory on admission. In addition, an information
      tool was completed on each CPP by the senior author. This tool listed demographic
      information, primary and secondary pain diagnoses, Diagnostic and Statistical
      Manual of Mental Disorders, 4th Edition (DSM-IV) psychiatric diagnoses assigned,
      pain location, pain precipitating event, type of injury, years in pain, number of
      surgeries, type of surgery, type of pain pattern, opioids consumed per day in
      morphine equivalents, worker compensation status, and whether, according to the
      clinical examination, the CPP had a neuropathic pain component. At completion of
      the multidisciplinary multimodal treatment, each CPP again completed the MFI.
      Student's t-test was utilized to test for statistical changes on the MFI five
      scales from pre- to post-treatment. Pearson and point-biserial correlations were
      utilized to determine which variables significantly correlated with MFI change
      scores. Variables found significant at less than or equal to 0.01 were utilized
      in a stepwise aggression analysis to find variables predictive of change in MFI
      scores. SETTING: Multidisciplinary pain facility. PATIENTS: Chronic LBP and
      chronic neck pain patients. RESULTS: Multidisciplinary multimodal treatment
      significantly improved CPP fatigue as measured by the MFI. The available
      variables utilized to predict fatigue best explained only a small percentage
      (28.9%) of the variance. Improvement in fatigue was related to NPS-10 scale
      scores (neuropathic pain) and a previous diagnosis of fibromyalgia. CONCLUSIONS:
      Multidisciplinary multimodal pain facility treatment improves chronic LBP- and
      neck pain-associated fatigue. At the present time we cannot predict this
      improvement with significant accuracy.

PMID- 16083461
TI  - Evidence-based oral transmucosal fentanyl citrate (OTFC) dosing guidelines.
AB  - OBJECTIVE: To review the evidence for dosing and efficacy of oral transmucosal
      fentanyl citrate in the management of pain and produce dosing guidelines. DESIGN:
      The scientific literature pertaining to oral transmucosal fentanyl citrate was
      reviewed, focusing upon its pharmacology and clinical experience with use in
      cancer and noncancer pain. Emphasis was upon published, peer-reviewed English
      language articles. RESULTS: Information was crucially examined and synthesized
      into guidelines for use and dosing of oral transmucosal fentanyl citrate in
      cancer and noncancer pain. CONCLUSIONS: Oral transmucosal fentanyl citrate is a
      potent opioid delivery system, which, when used appropriately, is an effective
      treatment option for pain. Adherence to guidelines should promote its safe and
      efficacious use in a variety of clinical pain management settings.

PMID- 16083462
TI  - Puzzling pain conditions: how philosophy can help us understand them.
AB  - CONTEXT: Pain is a complicated area of inquiry. To progress in our scientific
      understanding of the topic, it may be useful to learn how other disciplines are
      grappling with the subject. Philosophy is one discipline actively engaged in
      trying to understand pain. OBJECTIVE: We present one philosophical view of pain
      to help broaden the understanding of pain in those who are trained to look at it
      from a biomedical perspective. DISCUSSION: One current philosophical theory of
      pain is the externalist perceptual theory of pain. This theory states that pain
      is a form of perception and can be likened to other perceptions, for example,
      visual, tactile, etc. The way a pain feels can be explained as the relationship
      between this perception and some bodily damage occurring. and just as other
      perceptions can be mistaken, such as in a visual illusion, pain can also be
      inaccurate. We explore how the theory deals with puzzling conditions such as
      phantom limb pain, complex regional pain syndrome, and allodynia. We contrast
      this view with a competing theory of pain and briefly consider how these
      philosophical views may impact clinical medicine.

PMID- 16083463
TI  - "Puzzling pain conditions": a puzzling article.

PMID- 16083464
TI  - Treatment of intractable constipation with orlistat: a report of three cases.
AB  - Intractable constipation is a frequent side effect of opioid treatment of chronic
      pain. Orlistat, an FDA approved pill for weight loss, has gastrointestinal side
      effects including fecal incontinence, oily spotting, fecal urgency, and increased
      defecation. The author postulated that capitalizing on the known side effects of
      orlistat and prescribing orlistat to obese, chronic pain patients with opioid
      induced constipation would provide relief. The following report describes three
      positive cases of the use of orlistat for the treatment of opioid related
      constipation.

PMID- 16083465
TI  - The COMPLIANCE documentation aid.

PMID- 16083466
TI  - Clinical academic careers for nurses: time for a renewed debate.

PMID- 16083467
TI  - Nurse migration from Zimbabwe: analysis of recent trends and impacts.
AB  - The migration of nursing professionals from developing countries such as Zimbabwe
      to industrialised countries is taking place at an alarming rate, with little
      signs of slowing down. In Africa, nurses form the backbone of the healthcare
      delivery system and their migration has a huge negative impact on health service
      provision. Drawing on evidence from selected health institutions, the paper shows
      the magnitude of migration of nurses from Zimbabwe. The paper also shows that
      public to private health sector migration of nurses is occurring at a significant
      rate. The effects of such movements are examined in detail. For instance, at the
      health institution level, nurse migration has led to staff shortages, and health
      institutions located in the disadvantaged areas have been the worst affected. The
      paper calls for the adoption of an integrated approach in managing and addressing
      the concerns of the nursing professionals.

PMID- 16083468
TI  - Gender and embodiment in nursing: the role of the female chaperone in the
      infertility clinic.
AB  - This paper develops previous work on theories of embodiment by drawing on
      empirical data from a study into the experiences of infertile women in the UK. I
      suggest experiences of embodiment shape the preferences of infertile women for a
      female nurse as chaperone during intimate medical procedures. I explore the
      impact of this role on the understandings and meanings of nursing in a highly
      gendered field of practice. I present data from an ethnographic study of
      infertile women who chose to attend a British infertility clinic for
      investigation and fertility treatment cycles. Data were collected over 2 years
      using participant observation and semistructured interviews with 15 women and 20
      members of staff in a British fertility unit. Data analysis was completed using a
      modified thematic analysis following Boyle and McEvoy. I discuss women's
      experiences of intimacy and bodily care and how these experiences might be
      understood by exploring the phenomenological concept of embodiment. I argue that
      women benefit from having a female nurse as chaperone because of their
      expectations of gender, nursing and caring. Women's expectations reinforce both
      notions of gendered caring and the gendered role of nursing. These data challenge
      notions of patriarchal professionalism prevalent in nursing, which seek to move
      away from the gendered role of the nurse (which traditionally included a
      chaperone role) towards a model of professional development based on a mind-body
      split. I suggest that these data offer a way of understanding the female embodied
      subject in the field of gendered caring, which is potentially transgressive
      because they suggest ways in which both mind and body can be integrated through
      the role of the female chaperone.

PMID- 16083469
TI  - Risk bodies: rehabilitation of sports patients in the physiotherapy clinic.
AB  - This paper describes how body regimes are effectuated in the prevailing treatment
      strategy of physiotherapy. The process of self-mastering in the context of sports
      related injuries is highlighted. Through a Foucauldian perspective on body
      regimes the aim is to shed light on the process of individualization and self
      mastery in rehabilitation. The treatment of illness in the physiotherapy clinic
      does not characterize the patient as sick, and exempt the patient from daily
      duties and expectations. The empirical data include 17 qualitative illness
      narratives and several years of fieldwork observing patients with anterior
      cruciate ligament (ACL) injuries in a physiotherapy clinic. The study
      demonstrates how the expectation that the patients be active and self-mastering
      permeates the total process of treatment. The individual responsibility for
      personal well-being is a recurrent phenomenon in public health services in
      general, and specifically prominent in the rehabilitation of sports injuries.

PMID- 16083470
TI  - Perceived threat in compliance and adherence research.
AB  - Within the broader agenda of adherence research, health beliefs have been
      identified as being significant predictors of adherence. Specifically, perceived
      threat as a health belief has received considerable attention in compliance and
      adherence research from multiple perspectives in multiple patient populations.
      The purpose of this paper is to analyze the concept of perceived threat as it
      relates to treatment adherence through a series of perspectives: conceptual,
      methodological, and empirical. Analysis of the literature reveals that there is
      lack of consistency in operationalization of perceived threat as it relates to
      treatment adherence. Perceived threat is most commonly cited in studies that
      focus on health beliefs or utilize a stress and coping paradigm. Instruments have
      been developed with items that measure perceived threat. Measures of threat occur
      primarily through uni-dimensional measures that do not reflect the inter
      relatedness of the threat experience to personal and contextual factors. Future
      research examining perceived threat from a cognitive appraisal perspective, where
      both primary and secondary appraisals can be examined, may provide additional
      insight into factors affecting treatment adherence.

PMID- 16083471
TI  - Beyond dichotomies of health and illness: life after breast cancer.
AB  - While there has been a vast amount of research on breast cancer in recent years,
      areas within this domain remain unexplored. For instance, there have been few
      attempts to marry an understanding of the social context in which breast cancer
      occurs with an understanding of subjective experiences of this condition. The
      purpose of this study was to explore women's experiences of embodiment after
      breast cancer, utilizing a phenomenological approach rooted in a feminist
      perspective. The focus of this article is upon the changes to embodiment that are
      long-term. Twelve women were interviewed on two occasions each and were asked to
      talk about changes to their bodies that occurred as a result of breast cancer.
      Three key themes were identified: (1) how it feels (e.g. sensation and breast
      loss); (2) managing appearances (e.g. wearing prostheses); and (3) treatments
      without end (e.g. menopause). The findings of this study show that women with
      breast cancer are a diverse group and that survivorship is a dynamic, life-long
      process, which suggests that health professionals can play an important role in
      establishing interdisciplinary approaches to caring, beyond the conclusion of
      acute treatment.

PMID- 16083472
TI  - The family theory-practice gap: a matter of clarity?
AB  - Despite recognition of the importance of family in health-care and progress in
      family theory development, there has been limited transfer of family theory to
      acute care nursing practice. We argue that this family theory-practice gap
      results from a persistent lack of conceptual clarity in family nursing and other
      barriers. Lack of conceptual clarity takes the form of conceptual overlap and
      semantic inconsistency, as well as the complexity of language found in the family
      nursing literature. Barriers include practice contexts, relational problems, and
      knowledge types. Our exploration begins with a brief discussion of the intimate
      link between nursing theory and practice followed by an overview of some issues
      associated with the family nursing theory-practice gap. Based on a synthesis of
      family nursing literature, problems associated with conceptual clarity in family
      nursing theory are explored. We conclude with recommendations for family nursing
      research to develop concepts grounded in nursing practice.

PMID- 16083473
TI  - Reproducing normative and marginalized masculinities: adolescent male popularity
      and the outcast.
AB  - Every day, in professional work and in our personal lives, we reproduce by words
      and behaviors particular understandings of life and how it works. This includes
      understandings about what is 'normal' and 'not normal' masculinity and who are
      'normal' and 'not normal' boys and men. Being marginalized or outcast from the
      norm is rarely a free choice. The language that constructs normal and abnormal is
      not innocent and does not simply arrive in our minds transparently reflected in
      our behavior or in our client advice or student education. Examining words and
      behaviors from adolescent boys and from media sources, this research explores the
      role of cultural discourses in producing normative and marginalized
      masculinities. It builds upon recent scholarship that questions cultural
      prescriptions for masculinity and traditional male norms. Feminist,
      poststructural, psychoanalytic discourse analysis and multiple methods were used
      to explore links between cultural discourses of masculinity and performativity of
      masculinity. Practices of heterosexuality, homophobia, athleticism, economic
      privilege, toughness, and violence provided pathways toward achieving and/or
      maintaining status as the hegemonic masculine norm in adolescence. 'Popularity'
      signified the norm and 'outcasts' from the norm signified marginalized
      masculinities.

PMID- 16083474
TI  - The impact of the re-engineered world of health-care in Canada on nursing and
      patient outcomes.
AB  - The healthcare environment is knowledge driven and knowledge and human resource
      dependent. Despite the paucity of evidence on which to shape and evaluate
      organizational change, health-care in Canada has undergone many changes in the
      last 15 years. In the pursuit of enhanced productivity, healthcare administrators
      have turned to industrial and engineering models. Using available Canadian
      research and policy reports, and where necessary, American literature, this paper
      describes the impact of re-engineering on nursing and on the relationship between
      nursing and patient outcomes. It also identifies emerging trends and ways
      forward.

PMID- 16083476
TI  - The future is local and global.

PMID- 16083477
TI  - Issues and challenges in international doctoral education in nursing.
AB  - Education is a driving force in improving the health and welfare of communities
      globally. Doctoral education of nurses has been identified as a critical factor
      for provision of leadership in practice, scholarship, research, policy and
      education. Since the genesis of doctoral education in nursing in the USA in the
      1930s, this movement has burgeoned to over 273 doctoral programs in over 30
      countries globally. The present article seeks to identify the issues and
      challenges in nursing doctoral education globally, and those encountered by
      doctoral program graduates in meeting the challenges of contemporary health care
      systems. Information was derived from a comprehensive literature review.
      Electronic databases and the Internet, using the Google search engine, were
      searched using the key words "doctoral education"; "nursing"; "International
      Network for Doctoral Education in Nursing"; "global health"; "international
      research collaboration". Doctoral education has been a critical force in
      developing nurse leaders in education, management, policy and research domains.
      An absence of consensus in terminology and of accurate minimum data sets
      precludes comparison and debate across programs. The complexity and dynamism of
      contemporary globalized communities render significant challenges in the conduct
      of doctoral programs. Addressing funding issues and faculty shortages are key
      issues for doctoral programs, especially those in developing countries, to
      achieve an identity uniquely their own. These challenges can also afford
      considerable opportunities for discussion, debate and the formulation of
      innovative and collaborative solutions to advance nursing knowledge and
      scholarship. In spite of discrete differences between countries and regions, the
      similarities in the issues facing the development of doctoral programs
      internationally are more striking than the differences. The harnessing of a
      global collective to address these issues will likely serve to not only forge the
      future viability of doctoral education of nurses but to improve the health and
      well-being of communities. This paper proposes international collaborative
      strategies to address a number of the challenges identified.

PMID- 16083478
TI  - Influence of an asthma education program on parents with children suffering from
      asthma.
AB  - Several studies have evaluated the effectiveness of various methods of asthma
      education for parents. This study adds a qualitative and inner perspective from
      the families of children suffering from asthma. The aim was to illuminate the
      influence of an asthma education program (AEP) for parents. The study sample
      consisted of nine parents of five children with moderate to severe asthma in the
      2-6 years age group. Data were collected by interviews and qualitative analyses
      were used. The main findings were that the parents experienced an increased
      understanding of their child's experience of asthma after having participated in
      the program. Three themes were revealed: sharing experiences, accepting the
      illness, and partnership building. In conclusion, the parents in the study
      expressed that they promote increased self-understanding by meeting other parents
      in groups.

PMID- 16083479
TI  - Undergraduate nursing students' attitudes towards smoking health promotion.
AB  - Despite the fact that nurses have a key role in health promotion, many continue
      to smoke at much the same rate as the general population. This paper investigates
      the influence of smoking status, gender, age, stage of education, and smoking
      duration on undergraduate nursing students' attitudes towards smoking health
      promotion. The study took place in one university's School of Nursing in
      Victoria, Australia. Respondents completed the Smoking and Health Promotion
      instrument. Researchers obtained ethics approval prior to commencing the study.
      Smoking status was the main factor that affected respondents' attitudes towards
      smoking health promotion, with age and education stage having a minor effect, and
      gender and smoking duration not significant. Nurses have an important role in
      modeling non-smoking behaviors for patients. There needs to be consistency
      between personal and professional beliefs for nurses to properly engage in
      smoking health promotion. The findings have implications for undergraduate
      nursing education curricula, nursing practice and research, and these are
      discussed.

PMID- 16083480
TI  - Nurses' perceptions of discharge planning.
AB  - The present paper investigates what the term discharge planning actually means to
      nurses working in the acute care environment. A qualitative approach was used for
      this study. Twelve volunteer registered nurses (RNs) working in a large
      metropolitan Victorian public hospital were interviewed. All participants stated
      emphatically that they were involved in the discharge planning process although
      differing levels of involvement existed. "Organizing" and "planning" were key
      words used by participants to define the term discharge planning. All but one
      participant considered the nurse to be the coordinator of the discharge planning
      process. How participants communicated with other nursing staff regarding the
      discharge planning needs of individual patients depended on the policy of each
      individual ward. Communication was perceived to be a major factor that either
      enhanced or impeded the discharge planning process.

PMID- 16083481
TI  - Measuring symptom distress among frail elders capable of providing self reports.
AB  - This study aimed to develop a valid and reliable method of measuring symptom
      distress in frail elderly people capable of providing self reports. We tested a
      tool used in palliative care settings with 46 elders in residential aged care,
      refined the tool, and tested the new version with 48 additional elders. Items
      assessed the prevalence and severity of distress attributed to nausea; pain;
      insomnia; fatigue; and breathing, bowel and appetite problems in the first phase,
      and pain; insomnia; fatigue; and breathing, bowel, and bladder problems in the
      second phase. Participants rated symptom distress on a 10-point scale over 5
      days. Internal consistency reliability coefficients for the revised tool ranged
      from 0.50 to 0.64. Concurrent validity with an established measure of well-being
      was demonstrated. Further research will assess stability. The tool provides a
      valid overview of symptom distress in frail aged people able to provide self
      reports.

PMID- 16083482
TI  - Adolescents' perspectives on addiction: qualitative study.
AB  - Given that the adolescence period is one of the most crucial stages of
      development during one's lifetime and adolescents are prone to engage in
      behaviors which may negatively impact their health, it is very important to have
      a clear and transparent understanding of adolescents' health needs and problems.
      A content analysis with a qualitative approach was conducted and 41 healthy
      adolescents were interviewed. The results of this study revealed the following
      themes: addiction causes and prevalence; unhealthy friendship and communication
      and increased rates of cigarette smoking; alcohol and drugs; barriers to and
      factors in addiction and health; family and addiction. The findings showed
      worrying attitudes of adolescents to addiction and its prevalence are alarming.
      It is concluded that exploring adolescents' perspectives is not only important
      but is useful for maintaining a healthy society, and thus policy makers should
      develop effective prevention and intervention programs based on these themes.

PMID- 16083483
TI  - Effect of a self-directed learning package on emergency nurses' knowledge of
      assessment of oxygenation and use of supplemental oxygen.
AB  - Emergency nurses frequently and independently make decisions regarding
      supplemental oxygen. The importance of these decisions for patients is
      highlighted by the well documented association between respiratory dysfunction
      and adverse events. This study aimed to: (i) examine the effect of educational
      preparation on emergency nurses' knowledge of assessment of oxygenation, and the
      use of supplemental oxygen; (ii) explore the impact of existing knowledge on
      decisions related to the implementation of supplemental oxygen; and (iii) explore
      nurses' characteristics that were associated with effectiveness of the
      educational preparation. A pretest/post-test, controlled, quasi-experimental
      design was used in this study. Educational preparation was effective in
      increasing emergency nurses' knowledge. Baseline level of knowledge was
      predictive of reports of independent decisions regarding the implementation of
      oxygen. There was a significant positive relationship between postgraduate
      qualification in emergency nursing and the effect of education, and significant
      negative relationships between effect of education and baseline level of
      knowledge and daily decisions to implement supplemental oxygen.

PMID- 16083484
TI  - Nurses' job dissatisfaction and turnover intention: methodological myths and an
      alternative approach.
AB  - Job dissatisfaction and turnover are recurring themes in nursing. The current
      international nursing shortage has resulted in increased interest in
      investigating the causes of nurses' job dissatisfaction and turnover, and in
      developing countermeasures to address these issues. This paper involves a review
      of quantitative nursing studies, which investigated the causes of nurses' job
      dissatisfaction and turnover intention, and identifies commonly held myths that
      may inhibit more nurse-centered strategies from being developed. These myths are
      based on an assumption that a nurse-environment relationship is a one-way
      interaction in which nurses passively respond to their environment. The paper
      introduces the person-environment fit theory as an alternative framework, which
      challenges the assumption by suggesting it is the relationship between person and
      environment, rather than environmental characteristics alone, that affects
      nurses' occupational behavior. This theory enables nurse researchers to develop a
      more mutual approach involving the nurse and environment.

PMID- 16083486
TI  - Ageing, care dependency, and care for older people in Egypt: a review of the
      literature.
AB  - AIMS: The purpose of this study was to gain an overview of the current situation
      of ageing and elderly care in Egypt and to consider the ensuing socio-economical
      problems, which provide the framework for the provision of care. BACKGROUND:
      Recent discussions about demographic transition in developing countries suggest a
      change in their age group composition. Possible implications of this development
      for nursing care require closer examination. METHOD: Literature about ageing and
      elderly care in Egypt of the period from 1980-2004 was researched and reviewed.
      RESULTS: Despite the scarcity of literature and the lack of precision in many
      cases, it is possible to outline an overall development. Ageing is a slowly
      emerging phenomenon in Egypt contributing to a change in the country's age group
      composition. The ensuing care dependency appears to become a problem especially
      for lower and middle class members due to economical restrictions and life-style
      changes. In relation to the need, there is a shortage of care-providing
      institutions. Furthermore, geriatric homes seem to differ in their quality
      according to the residents' social status. CONCLUSION: The existing types of
      geriatric homes will serve as prototypes for future development. There is
      however, a need for additional homecare services to reduce care givers' strain in
      the families.

PMID- 16083487
TI  - Older people's views of prioritization in health care. The applicability of an
      interview study.
AB  - AIM: Older people's views of prioritization in health care. The applicability of
      an interview study. Old age has been stated as a criterion for prioritization in
      health care, although older people are seldom asked for their opinions. The aim
      of this pilot study was to investigate the applicability of a questionnaire as a
      base for an interview study to explore older people's experiences and views of
      prioritization in health care. DESIGN: Descriptive, with a qualitative and
      quantitative approach. Fifty-four persons, 32 women and 22 men (aged 60-93
      years), were asked to participate in a structured, tape-recorded interview
      covering their experience and views of the priorities applied in health care.
      RESULTS: The questions in the interview manual appeared to be applicable for
      collecting data concerning views of prioritization, but the analysis revealed
      that certain questions, particularly on economic matters, were missing. The
      procedure, a personal structured interview had advantages, for example, in
      capturing the respondents' reflections on the questions. The respondents
      emphasized the equal value of all human beings and that age is not a basis for
      prioritization within health care. The respondents also showed an unwillingness
      to precede anyone in rank. IMPLICATIONS: The questions used proved to be adequate
      but to be really complete further questions need to be added. This pilot study
      indicates that older people's views on priorities in health care differ from
      those expressed by the younger population. The study therefore needs to be
      replicated in a larger sample to be fully able to understand older people's views
      of prioritization, which will require exploring gender and age differences as
      well as other aspects that may explain variations.

PMID- 16083488
TI  - The clinical learning portfolio: a practice development experience in
      gerontological nursing.
AB  - BACKGROUND: Assessment of clinical practice in post registration programmes can
      require a different focus to capture the essence of learning at a higher level.
      There are differences of opinion in the literature on the potential use of the
      portfolio as an assessment method. AIMS: The aims of this paper are to describe
      the use of a portfolio of evidence-based practice and reflection to assess
      clinical learning in a Higher Diploma in Gerontological Nursing Programme and to
      present the findings of a pilot evaluation of this assessment. DESIGN AND METHOD:
      The evaluation was conducted by postal questionnaire distributed to the first
      cohort of students following graduation from the programme in 2002. RESULTS AND
      CONCLUSIONS: Arising from this exploration of the student experience, it appears
      that the use of a portfolio in addition to formative assessment, can promote a
      link between theory and the advancement of gerontological nursing practice.

PMID- 16083489
TI  - The content of morning time conversations between nursing home staff and
      residents.
AB  - AIM: The aim of this paper was to investigate what nursing home staff and
      residents converse about when they first meet each other in the morning and to
      investigate who starts the conversation. It is a pilot project about
      communication in a nursing home in Sweden and a basis for a practice development
      programme. BACKGROUND: Studies in Sweden have shown that nurse assistants working
      in care of the older people felt they had too little training in how to
      communicate. Communicative behaviour influences patients, but little is known
      about the content of morning time communication in nursing homes. METHOD: Non
      participant observation of 18 staff was carried out using an observation schema.
      Content analysis was performed. RESULTS: The findings were that it was the staff
      who initiated conversation and chose the content of conversation. The most common
      topic in morning time conversation was residents' health and sickness.
      CONCLUSION: Staff in nursing homes, both nurses and nurse assistants need to
      reflect on their interaction with residents and be conscious of their important
      role because they create the climate on the ward through conversation. Further
      studies are needed in order to explore residents' opinions of what the content of
      a good communication could be and also to find out how nurses and other staff
      members' communication with residents could be improved. Relevance to clinical
      practice. Staff need more training and knowledge about how to communicate with
      older people.

PMID- 16083490
TI  - The meaning of work for nursing assistants who stay in long-term care.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to investigate the meaning of
      work for nursing assistants who stay in long-term care. BACKGROUND: Nursing
      assistants are important caregivers in long-term agencies. While studies have
      examined why nursing assistants leave, their motivation to stay has not been well
      studied. DESIGN: An existential-phenomenological study was conducted using
      Pollio's approach. METHODS: In-depth interviews were conducted with 11 nursing
      assistants in four nursing homes. Interviews were analysed within the context of
      an interpretive research group. Findings were represented in a diagram of
      interrelated figural/ground themes. CONCLUSIONS: The meaning of work emerged as
      an experience of family, pride and control, in spite of an environment fraught
      with hostility, disrespect and lack of control. RELEVANCE TO CLINICAL PRACTICE:
      Nursing assistants provide most of the care to residents of long-term facilities.
      Understanding their perspective offers insight into nursing administrators in
      creating environments in which safe, compassionate and cost-effective care co
      exist. Implications for clinical practice are framed within King's theory of goal
      attainment.

PMID- 16083492
TI  - Conceptualizing place in the care of older people: the contributions of
      geographical gerontology.
AB  - This paper introduces the subdiscipline of geographical gerontology to the
      readers of International Journal of Older People Nursing, and the ways in which
      geographers and others have conceptualized place in relation to the experiences
      of older people and their health and well-being. Particular attention is paid to
      place as a process; its role in the exertion and negotiation of power; and as an
      experience open to interpretation; and how these relate to clinical
      practitioners. This review sets the scene for the following papers on practice
      and the future research agenda.

PMID- 16083493
TI  - 'Airplanes are flying nursing homes': geographies in the concepts and locales of
      gerontological nursing practice.
AB  - With the geographical literatures and issues outlined in the first paper very
      much in mind, this paper focuses specifically on the places in the concepts and
      locales of gerontological nursing practice. Particular attention is paid to the
      role of nurses in the making of long-term care institutions and to some
      fundamental priorities of care. Consideration is also given to some broader
      impacts of neighbourhood and community as an important spatial context to nursing
      practice based both in institutions and the community. In the final section, the
      paper makes some observations on how place-sensitive practice and research might
      contribute to the uptake of evidence for practice. These discussions set the
      scene for the final paper in this special section focused on the future research
      agenda for place and older people nursing.

PMID- 16083494
TI  - Spaces for inquiry into the role of place for older people's care.
AB  - In this paper, I expand the scope of the two preceding papers and suggest
      emerging opportunities and needs relevant to future inquiry about place and older
      people. I cover these in three sections. The first section suggests several
      topical areas for inquiry: stress and health, social epidemiology and healthy
      ageing. The second section focuses on theoretical developments that could be
      extended to further inform research on place and older people. I discuss the
      concepts of therapeutic landscapes and home as well as actor-network theory and
      pragmatism. The last section briefly addresses methodological needs. I contend
      that while place is a complex object of inquiry, it is vital to older adults'
      well-being and offers many interesting and interdisciplinary avenues for
      important scholarly endeavour in nursing and related fields.

PMID- 16083495
TI  - Novel curcumin- and emodin-related compounds identified by in silico 2D/3D
      conformer screening induce apoptosis in tumor cells.
AB  - BACKGROUND: Inhibition of the COP9 signalosome (CSN) associated kinases CK2 and
      PKD by curcumin causes stabilization of the tumor suppressor p53. It has been
      shown that curcumin induces tumor cell death and apoptosis. Curcumin and emodin
      block the CSN-directed c-Jun signaling pathway, which results in diminished c-Jun
      steady state levels in HeLa cells. The aim of this work was to search for new CSN
      kinase inhibitors analogue to curcumin and emodin by means of an in silico
      screening method. METHODS: Here we present a novel method to identify efficient
      inhibitors of CSN-associated kinases. Using curcumin and emodin as lead
      structures an in silico screening with our in-house database containing more than
      10(6) structures was carried out. Thirty-five compounds were identified and
      further evaluated by the Lipinski's rule-of-five. Two groups of compounds can be
      clearly discriminated according to their structures: the curcumin-group and the
      emodin-group. The compounds were evaluated in in vitro kinase assays and in cell
      culture experiments. RESULTS: The data revealed 3 compounds of the curcumin-group
      (e.g. piceatannol) and 4 of the emodin-group (e.g. anthrachinone) as potent
      inhibitors of CSN-associated kinases. Identified agents increased p53 levels and
      induced apoptosis in tumor cells as determined by annexin V-FITC binding, DNA
      fragmentation and caspase activity assays. CONCLUSION: Our data demonstrate that
      the new in silico screening method is highly efficient for identifying potential
      anti-tumor drugs.

PMID- 16083496
TI  - Stoichiometric estimates of the biochemical conversion efficiencies in tsetse
      metabolism.
AB  - BACKGROUND: The time varying flows of biomass and energy in tsetse (Glossina) can
      be examined through the construction of a dynamic mass-energy budget specific to
      these flies but such a budget depends on efficiencies of metabolic conversion
      which are unknown. These efficiencies of conversion determine the overall yields
      when food or storage tissue is converted into body tissue or into metabolic
      energy. A biochemical approach to the estimation of these efficiencies uses
      stoichiometry and a simplified description of tsetse metabolism to derive
      estimates of the yields, for a given amount of each substrate, of conversion
      product, by-products, and exchanged gases. This biochemical approach improves on
      estimates obtained through calorimetry because the stoichiometric calculations
      explicitly include the inefficiencies and costs of the reactions of conversion.
      However, the biochemical approach still overestimates the actual conversion
      efficiency because the approach ignores all the biological inefficiencies and
      costs such as the inefficiencies of leaky membranes and the costs of molecular
      transport, enzyme production, and cell growth. RESULTS: This paper presents
      estimates of the net amounts of ATP, fat, or protein obtained by tsetse from a
      starting milligram of blood, and provides estimates of the net amounts of ATP
      formed from the catabolism of a milligram of fat along two separate pathways, one
      used for resting metabolism and one for flight. These estimates are derived from
      stoichiometric calculations constructed based on a detailed quantification of the
      composition of food and body tissue and on a description of the major metabolic
      pathways in tsetse simplified to single reaction sequences between substrates and
      products. The estimates include the expected amounts of uric acid formed, oxygen
      required, and carbon dioxide released during each conversion. The calculated
      estimates of uric acid egestion and of oxygen use compare favorably to published
      experimental measurements. CONCLUSION: This biochemical analysis provides
      reasonable first estimates of the conversion efficiencies for the major pathways
      used by tsetse metabolism. These results now enable a deeper analysis of tsetse
      ecology based on the construction of a dynamic mass-energy budget for tsetse and
      their populations.

PMID- 16083497
TI  - Cocaine in surface waters: a new evidence-based tool to monitor community drug
      abuse.
AB  - BACKGROUND: Cocaine use seems to be increasing in some urban areas worldwide, but
      it is not straightforward to determine the real extent of this phenomenon. Trends
      in drug abuse are currently estimated indirectly, mainly by large-scale social,
      medical, and crime statistics that may be biased or too generic. We thus tested a
      more direct approach based on 'field' evidence of cocaine use by the general
      population. METHODS: Cocaine and its main urinary metabolite (benzoylecgonine,
      BE) were measured by mass spectrometry in water samples collected from the River
      Po and urban waste water treatment plants of medium-size Italian cities. Drug
      concentration, water flow rate, and population at each site were used to estimate
      local cocaine consumption. RESULTS: We showed that cocaine and BE are present,
      and measurable, in surface waters of populated areas. The largest Italian river,
      the Po, with a five-million people catchment basin, steadily carried the
      equivalent of about 4 kg cocaine per day. This would imply an average daily use
      of at least 27 +/- 5 doses (100 mg each) for every 1000 young adults, an estimate
      that greatly exceeds official national figures. Data from waste water treatment
      plants serving medium-size Italian cities were consistent with this figure.
      CONCLUSION: This paper shows for the first time that an illicit drug, cocaine, is
      present in the aquatic environment, namely untreated urban waste water and a
      major river. We used environmental cocaine levels for estimating collective
      consumption of the drug, an approach with the unique potential ability to monitor
      local drug abuse trends in real time, while preserving the anonymity of
      individuals. The method tested here--in principle extendable to other drugs of
      abuse--might be further refined to become a standardized, objective tool for
      monitoring drug abuse.

PMID- 16083498
TI  - Clinico-pathological features of bladder carcinoma in women in Pakistan and
      smokeless tobacco as a possible risk factor.
AB  - BACKGROUND: Bladder carcinoma is one of the common urological malignancies
      occurring worldwide in both sexes. Use of smokeless tobacco by women is common in
      rural areas of Pakistan. The clinico-pathological features of bladder carcinoma
      in women and association of smokeless tobacco as a possible risk factor for
      bladder carcinoma has not been well described in the literature. The objective of
      the study was to determine the clinico-pathological features of histologically
      confirmed bladder carcinoma in women and to investigate the role of smokeless
      tobacco use as a possible risk factor for its development. PATIENTS AND METHODS:
      Of the 204 patients (160 male and 44 female M:F ratio 3.6:1) of newly diagnosed
      bladder carcinoma treated at Nishtar Medical College Hospital Multan from January
      1998 to December 2004, the 44 female patients were evaluated with respect to age,
      clinical presentation, cystoscopic findings, histopathological reports and
      possible etiological factors. Data were collected and prospectively updated at
      the time of discharge from hospital and during follow-up in urology out-patient
      clinic. RESULTS: Transitional cell carcinoma accounted for all of the bladder
      carcinoma in women. Median age of the patients was 55 years and 68% patients were
      under 60 years of age. Majority of patients (88%) presented with hematuria.
      Eleven (25%) patients had superficial (pTa/pT1) while 33 (75%) patients had
      muscle invasive (T2-T4) bladder carcinoma. Most (81%) superficial tumors were
      papillary while muscle invasive tumors had solid configuration at cystoscopy. Of
      these, 21 (47%) patients had long history of smokeless tobacco use (chewable or
      moist snuff). CONCLUSION: Transitional cell carcinoma is the most common bladder
      malignancy in women in Pakistan. Many women with bladder carcinoma had long
      history of use of smokeless tobacco. Majority of patients presented with
      hematuria and were under 60 years of age. At the time of diagnosis 75% women had
      muscle invasive bladder carcinoma. In women using smokeless tobacco, the
      correlation between stage of bladder carcinoma and duration of smokeless tobacco
      use was significant (p = 0.03). Further studies are needed to clarify the role of
      smokeless tobacco in the development of bladder carcinoma.

PMID- 16083499
TI  - Pancreatic stellate cells (PSCs) express cyclooxygenase-2 (COX-2) and pancreatic
      cancer stimulates COX-2 in PSCs.
AB  - BACKGROUND: Cyclooxygenase 2 (COX-2), the inducible form of prostaglandin G/H
      synthase, is associated with several human cancers including pancreatic
      adenocarcinoma. Pancreatic stellate cells (PSCs) play a central role in the
      intense desmoplasia that surrounds pancreatic adenocarcinoma. The present study
      examined COX-2 expression in PSCs. PSCs isolated from normal rats, were cultured
      and exposed to conditioned medium (CM) from the human pancreatic cell line, PANC
      1. METHODS: COX-2 expression was evaluated by immunostaining and western
      blotting. Proliferation of PSCs was determined by thymidine incorporation and
      cell counting. RESULTS: COX-2 was found to be constitutively expressed in PSCs,
      and COX-2 protein was up-regulated by PANC-1 CM. Moreover, the induction of COX-2
      by PANC-1 CM was prevented by U0126, an extracellular signal-regulated kinase
      (ERK) 1/2 inhibitor suggesting that activation of ERK 1/2 is needed for
      stimulation of COX-2. Finally, NS398, a selective COX-2 inhibitor, reduced the
      growth of PSCs by PANC-1 CM, indicating that activation of COX-2 is required for
      cancer stimulated PSC proliferation. CONCLUSION: The results suggest that COX-2
      may play an important role in the regulation of PSC proliferation in response to
      pancreatic cancer.

PMID- 16083500
TI  - FIGENIX: intelligent automation of genomic annotation: expertise integration in a
      new software platform.
AB  - BACKGROUND: Two of the main objectives of the genomic and post-genomic era are to
      structurally and functionally annotate genomes which consists of detecting genes'
      position and structure, and inferring their function (as well as of other
      features of genomes). Structural and functional annotation both require the
      complex chaining of numerous different software, algorithms and methods under the
      supervision of a biologist. The automation of these pipelines is necessary to
      manage huge amounts of data released by sequencing projects. Several pipelines
      already automate some of these complex chaining but still necessitate an
      important contribution of biologists for supervising and controlling the results
      at various steps. RESULTS: Here we propose an innovative automated platform,
      FIGENIX, which includes an expert system capable to substitute to human expertise
      at several key steps. FIGENIX currently automates complex pipelines of structural
      and functional annotation under the supervision of the expert system (which
      allows for example to make key decisions, check intermediate results or refine
      the dataset). The quality of the results produced by FIGENIX is comparable to
      those obtained by expert biologists with a drastic gain in terms of time costs
      and avoidance of errors due to the human manipulation of data. CONCLUSION: The
      core engine and expert system of the FIGENIX platform currently handle complex
      annotation processes of broad interest for the genomic community. They could be
      easily adapted to new, or more specialized pipelines, such as for example the
      annotation of miRNAs, the classification of complex multigenic families,
      annotation of regulatory elements and other genomic features of interest.

PMID- 16083501
TI  - Tumor suppressor in lung cancer 1 (TSLC1) alters tumorigenic growth properties
      and gene expression.
AB  - BACKGROUND: Introduction of cDNA or genomic clones of the tumor suppressor in
      lung cancer 1 (TSLC1) gene into the non-small cell lung cancer line, A549,
      reverses tumorigenic growth properties of these cells. These results and the
      observation that TSLC1 is down-regulated in a number of tumors suggest that TSLC1
      functions as a critical switch mediating repression of tumorigenesis. RESULTS: To
      investigate this mechanism, we compared growth properties of A549 with the TSLC1
      containing derivative. We found a G1/S phase transition delay in 12.2.
      Subtractive hybridization, quantitative PCR, and TranSignal Protein/DNA arrays
      were used to identify genes whose expression changed when TSLC1 was up-regulated.
      Members of common G1/S phase regulatory pathways such as TP53, MYC, RB1 and HRAS
      were not differentially expressed, indicating that TSLC1 may function through an
      alternative pathway(s). A number of genes involved in cell proliferation and
      tumorigenesis were differentially expressed, notably genes in the Ras-induced
      senescence pathway. We examined expression of several of these key genes in human
      tumors and normal lung tissue, and found similar changes in expression,
      validating the physiological relevance of the A549 and 12.2 cell lines.
      CONCLUSION: Gene expression and cell cycle differences provide insights into
      potential downstream pathways of TSLC1 that mediate the suppression of tumor
      properties in A549 cells.

PMID- 16083502
TI  - Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a
      comprehensive review.
AB  - Many women experience vasomotor symptoms at or around the time of menopause. Hot
      flushes and night sweats are considered primary menopausal symptoms that may also
      be associated with sleep and mood disturbances, as well as decreased cognitive
      function. All of these symptoms may lead to social impairment and work-related
      difficulties that significantly decrease overall quality of life. Hot flushes
      have shown a great deal of variability in their frequency and severity in women.
      In some women, hot flushes persist for several months; in others, they may last
      for more than 10 years. Traditionally vasomotor symptoms were reported to begin 5
      to 10 years prior to the cessation of the final menstrual cycle, corresponding
      with the initial decline in circulating gonadal hormones; however, night sweats
      in particular most often begin in perimenopause. The pathogenesis of hot flushes
      has not yet been fully elucidated, but the circuitry involving estrogen and
      neurotransmitters, norepinephrine and serotonin specifically, are hypothesized to
      play a major role in the altered homeostatic thermoregulatory mechanisms
      underlying these events. Menopause-associated vasomotor symptoms are associated
      with significant direct and indirect costs. Overall costs of traditional
      pharmacotherapy or complementary and alternative medicine modalities, including
      over-the-counter treatments and dietary supplements, for managing menopause
      related vasomotor symptoms are substantial and include initial and follow-up
      physician visits and telephone calls. Additional costs include laboratory
      testing, management of adverse events, loss of productivity at work, and personal
      and miscellaneous costs. Pharmacoeconomic analyses, including those that consider
      risks identified by the Women's Health Initiative, generally support the cost
      effectiveness of hormonal therapy for menopause-associated vasomotor symptoms,
      which have been the mainstay for the management of these symptoms for more than
      50 years. However, because many women now want to avoid hormone therapy, there is
      a need for additional targeted therapies, validated by results from controlled
      clinical trials that are safe, efficacious, cost-effective, and well tolerated by
      symptomatic menopausal women.

PMID- 16083504
TI  - Predictors of failed attendances in a multi-specialty outpatient centre using
      electronic databases.
AB  - BACKGROUND: Failure to keep outpatient medical appointments results in
      inefficiencies and costs. The objective of this study is to show the factors in
      an existing electronic database that affect failed appointments and to develop a
      predictive probability model to increase the effectiveness of interventions.
      METHODS: A retrospective study was conducted on outpatient clinic attendances at
      Tan Tock Seng Hospital, Singapore from 2000 to 2004. 22864 patients were randomly
      sampled for analysis. The outcome measure was failed outpatient appointments
      according to each patient's latest appointment. RESULTS: Failures comprised of
      21% of all appointments and 39% when using the patients' latest appointment.
      Using odds ratios from the mutliple logistic regression analysis, age group (0.75
      to 0.84 for groups above 40 years compared to below 20 years), race (1.48 for
      Malays, 1.61 for Indians compared to Chinese), days from scheduling to
      appointment (2.38 for more than 21 days compared to less than 7 days), previous
      failed appointments (1.79 for more than 60% failures and 4.38 for no previous
      appointments, compared with less than 20% failures), provision of cell phone
      number (0.10 for providing numbers compared to otherwise) and distance from
      hospital (1.14 for more than 14 km compared to less than 6 km) were significantly
      associated with failed appointments. The predicted probability model's diagnostic
      accuracy to predict failures is more than 80%. CONCLUSION: A few key variables
      have shown to adequately account for and predict failed appointments using
      existing electronic databases. These can be used to develop integrative
      technological solutions in the outpatient clinic.

PMID- 16083503
TI  - A systematic search for new mammalian noncoding RNAs indicates little conserved
      intergenic transcription.
AB  - BACKGROUND: Systematic identification and functional characterization of novel
      types of noncoding (nc)RNA in genomes is more difficult than it is for protein
      coding mRNAs, since ncRNAs typically do not possess sequence features such as
      splicing or translation signals, or long open reading frames. Recent "tiling"
      microarray studies have reported that a surprisingly larger proportion of
      mammalian genomes is transcribed than was previously anticipated. However, these
      non-genic transcripts often appear to be low in abundance, and their functional
      significance is not known. RESULTS: To systematically search for functional
      ncRNAs, we designed microarrays to detect 3,478 intergenic and intronic sequences
      that are conserved between the human, mouse, and rat genomes, and that score
      highly by other criteria that characterize ncRNAs. We probed these arrays with
      total RNA isolated from 16 wild-type mouse tissues. Among 55 candidates for
      highly-expressed novel ncRNAs tested by northern blotting, eight were confirmed
      as small, highly-and ubiquitously-expressed RNAs in mouse. Of the eight, five
      were also detected in rat tissues, but none were detected at appreciable levels
      in human tissues or cultured cells. CONCLUSION: Since the sequence and expression
      of most known coding transcripts and functional ncRNAs is conserved between human
      and mouse, the lack of northern-detectable expression in human cells and tissues
      of the novel mouse and rat ncRNAs that we identified suggests that they are not
      functional or possibly have rodent-specific functions. Our results confirm that
      relatively little of the intergenic sequence conserved between human, mouse and
      rat is transcribed at high levels in mammalian tissues, possibly suggesting a
      limited role for transcribed intergenic and intronic sequences as independent
      functional elements.

PMID- 16083505
TI  - Need for enforcement of ethicolegal education - an analysis of the survey of
      postgraduate clinical trainees.
AB  - BACKGROUND: The number of medical lawsuits in Japan was between 14 and 21 each
      year before 1998, but increased to 24 to 35 per year after 1999. There were 210
      lawsuits during this 10-year period. There is a need for skills and knowledge
      related to ethics, which is as fundamental to the practice of medicine as basic
      sciences or clinical skills. In Japan education in ethics is relatively rare and
      its importance is not yet recognized. Establishing ethics education using legal
      precedents, which has already been achieved in Western countries, will be a very
      important issue in Japan. In the present study, a questionnaire survey was
      conducted among graduate intern doctors, in order to investigate whether ethics
      education using precedents might have a positive effect in Japan. METHODS: In
      2002, a questionnaire survey entitled Physicians' Clinical Ethics was carried out
      in a compulsory orientation lecture given to trainees before they started
      clinical practice in our hospital. The attendees at this lecture were trainees
      who came from colleges in various districts of Japan. During the lecture, 102
      questionnaires were distributed, completed by attendees and collected. The
      recovery rate was 100%. The questionnaire consisted of 22 questions (in three
      categories), of which 20 were answered by multiple choices, and the other two
      were answered by description. The time required to complete the questionnaire was
      about 10 minutes. RESULTS: The recovered questionnaires were analyzed using
      statistical analysis software (SPSS for Windows, Release 10.07J-1/June/2000), in
      addition to simple statistical analysis. answers using multiple choices for the
      20 questions in the questionnaire were input into SPSS. The principal component
      analysis was performed for each question. As a result, the item that came to the
      fore was "legal precedent". Since many intern doctors were interested in
      understanding laws and precedents, learning about ethical considerations through
      education using precedents might better meet with their needs and interests.
      CONCLUSION: We applied a new method in which the results of principal component
      analysis and frequencies of answers to other questions were combined. From this
      we deduced that the precedent education used in Western countries was useful to
      help doctors acquire ethical sensitivity and was not against their will. A
      relationship was found between reading precedents and the influence of lawsuits,
      and it was thought that student participation-type precedent education would be
      useful for doctors in order to acquire ethical sensitivity.

PMID- 16083506
TI  - Genetic polymorphism of the N-acetyltransferase 2 gene, and susceptibility to
      prostate cancer: a pilot study in north Indian population.
AB  - BACKGROUND: N-acetyltransferase 2 is phase II metabolizing enzyme that
      participates in the bioconversion of heterocyclic arylamines into electrophilic
      nitrenium ions, which are important ultimate carcinogens that are directly
      implicated in tumor initiation process. This study was conducted to examine; (1)
      whether the N-acetyltransferase 2 (NAT2) genotype is a risk factor for prostate
      cancer, (2) to study effect of NAT2 genotype on modifying prostate cancer risk
      from tobacco use. METHODS: The case control study was undertaken over a period of
      28 months and included 130 prostate cancer patients (CaP) and 140 controls. The
      NAT2 genotypes were identified by PCR-RFLP method in DNA extracted from
      peripheral blood. Genotype frequencies and the association of genotypes with
      patients and control groups were assessed by logistic regression model. RESULTS:
      We observed non-significant association of rapid acetylator genotype NAT2 (OR =
      1.452, 95% CI: 0.54-1.87, P = 0.136) in prostate cancer patients. However
      significant association was observed between rapid acetylator genotype NAT2 and
      CaP tobacco users (OR = 3.43, 95% CI: 1.68-7.02, P-value < 0.001) when compared
      with controls. CONCLUSION: The data suggests that the NAT2 rapid acetylator
      genotypes may play an important role in determining the risk of developing
      prostate cancer particularly in the tobacco users of north Indian population.

PMID- 16083507
TI  - Artificial neural networks for diagnosis and survival prediction in colon cancer.
AB  - ANNs are nonlinear regression computational devices that have been used for over
      45 years in classification and survival prediction in several biomedical systems,
      including colon cancer. Described in this article is the theory behind the three
      layer free forward artificial neural networks with backpropagation error, which
      is widely used in biomedical fields, and a methodological approach to its
      application for cancer research, as exemplified by colon cancer. Review of the
      literature shows that applications of these networks have improved the accuracy
      of colon cancer classification and survival prediction when compared to other
      statistical or clinicopathological methods. Accuracy, however, must be exercised
      when designing, using and publishing biomedical results employing machine
      learning devices such as ANNs in worldwide literature in order to enhance
      confidence in the quality and reliability of reported data.

PMID- 16083508
TI  - Evolution of a microbial nitrilase gene family: a comparative and environmental
      genomics study.
AB  - BACKGROUND: Completed genomes and environmental genomic sequences are bringing a
      significant contribution to understanding the evolution of gene families,
      microbial metabolism and community eco-physiology. Here, we used comparative
      genomics and phylogenetic analyses in conjunction with enzymatic data to probe
      the evolution and functions of a microbial nitrilase gene family. Nitrilases are
      relatively rare in bacterial genomes, their biological function being unclear.
      RESULTS: We examined the genetic neighborhood of the different subfamily genes
      and discovered conserved gene clusters or operons associated with specific
      nitrilase clades. The inferred evolutionary transitions that separate nitrilases
      which belong to different gene clusters correlated with changes in their
      enzymatic properties. We present evidence that Darwinian adaptation acted during
      one of those transitions and identified sites in the enzyme that may have been
      under positive selection. CONCLUSION: Changes in the observed biochemical
      properties of the nitrilases associated with the different gene clusters are
      consistent with a hypothesis that those enzymes have been recruited to a novel
      metabolic pathway following gene duplication and neofunctionalization. These
      results demonstrate the benefits of combining environmental genomic sampling and
      completed genomes data with evolutionary and biochemical analyses in the study of
      gene families. They also open new directions for studying the functions of
      nitrilases and the genes they are associated with.

PMID- 16083509
TI  - Complications after cryosurgery with new miniature cryoprobes in long hollow
      bones: an animal trial.
AB  - BACKGROUND: In vitro studies show that new miniature cryoprobes are suitable for
      cryoablation of bone tissue. The aim of this animal trial on 24 sheep was to
      examine the perioperative complications, particularly the danger of embolism, of
      cryoablation when using miniature cryoprobes. METHODS: Cryoablations with 2
      freeze-thaw cycles each were carried out in the epiphysis of the right tibia and
      the metaphysis of the left femur. Pulmonary artery pressure (PAP) and central
      venous pressure (CVP) were measured. Throughout the intra- and perioperative
      phase, heart rate and oxygen saturation by pulse oxymetry, blood gas and
      electrolytes were monitored regularly. Postoperative complications were examined
      up to 24 weeks postoperative. RESULTS: As result, no significant increase of PAP,
      CVP or heart rate were observed. Blood gases were unremarkable, with pO2 and pCO2
      remaining constant throughout the operation. Regarding pH, standard bicarbonate
      and base excess, only a non-significant shift towards a slight acidosis was seen.
      There was a mean hemoglobin decrease of 0.5 g/dl. One animal showed postoperative
      wound infection and wound edge necrosis. No major peri- and postoperative
      complications associated with cryosurgery of bone were observed, especially
      regarding clinically relevant pulmonary embolism. CONCLUSION: Surgery with new
      types of miniature cryoprobes appears to be a safe alternative to or a complement
      to conventional resection of abnormal bone tissue.

PMID- 16083510
TI  - Chromosomal changes in uroepithelial carcinomas.
AB  - This article reviews and summarizes chromosomal changes responsible for the
      initiation and progression of uroepithelial carcinomas. Characterization of these
      alterations may lead to a better understanding of the genetic mechanisms and open
      the door for molecular markers that can be used for better diagnosis and
      prognosis of the disease. Such information might even help in designing new
      therapeutic strategies geared towards prevention of tumor recurrences and more
      aggressive approach in progression-prone cases. The revision of 205 cases of
      uroepithelial carcinomas reported with abnormal karyotypes showed karyotypic
      profile characterized by nonrandom chromosomal aberrations varying from one or
      few changes in low-grade and early stage tumors to massively rearranged
      karyotypes in muscle invasive ones. In general, the karyotypic profile was
      dominated by losses of chromosomal material seen as loss of entire chromosome
      and/or deletions of genetic materials. Rearrangements of chromosome 9 resulting
      in loss of material from 9p, 9q, or of the entire chromosome were the most
      frequent cytogenetic alterations, seen in 45% of the cases. Whereas loss of
      material from chromosome arms 1p, 8p, and 11p, and gains of chromosome 7, and
      chromosome arm 1q, and 8q seem to be an early, but secondary, changes appearing
      in superficial and well differentiated tumors, the formation of an isochromosome
      for 5p and loss of material from 17p are associated with more aggressive tumor
      phenotypes. Upper urinary tract TCCs have identical karyotypic profile to that of
      bladder TCCs, indicating the same pathogenetic mechanisms are at work in both
      locales. Intratumor cytogenetic heterogeneity was not seen except in a few post
      radiation uroepithelial carcinomas in which distinct karyotypic and clonal
      pattern were characterized by massive intratumor heterogeneity (cytogenetic
      polyclonality) with near-diploid clones and simple balanced and/or unbalanced
      translocations. In the vast majority of cases strong correlation between the
      tumors grade/stage and karyotypic complexity was seen, indicating that
      progressive accumulation of acquired genetic alterations is the driving force
      behind multistep bladder TCC carcinogenesis. Although most of these cytogenetic
      alterations have been identified for many years, the molecular consequences and
      relevant cancer genes of these alterations have not yet been identified. However,
      loss of TSG(s) from chromosome 9 seems to be the primary and important event(s)
      in uroepithelial carcinogenesis.

PMID- 16083511
TI  - Hyperprolactinemia after laparoscopic ovarian drilling: an unknown phenomenon.
AB  - BACKGROUND: The effects of ovarian drilling on the serum levels of gonadotropins
      and androgens have been studied previously. The aim of this study is to evaluate
      the effects of ovarian drilling on the serum prolactin levels and its relation to
      ovulation in women with polycystic ovary syndrome. METHODS: This is a prospective
      controlled study. Thirty-six women with PCOS underwent ovarian
      electrocauterization in university hospitals. Control group consisted of 35
      ovulatory women with unexplained infertility. Hormonal assessment performed in
      early follicular phase of spontaneous or induced cycle before operation in the
      two groups and repeated one week after operation. Hormonal assay was also
      performed in the early follicular phase of the first post-operative menstruation,
      folliculometry and progesterone assay were also performed in the same cycle. Data
      were analyzed by "repeated measurement design, discriminant analysis, correlation
      coefficient, and Fisher exact test". RESULTS: Six to ten weeks after operation
      the serum mean +/- SD prolactin levels increased from 284.41 +/- 114.32 mIU/ml to
      354.06 +/- 204.42 mIU/ml (P = 0.011). The same values for the control group were
      277.73 +/- 114.65 to 277.4 +/- 111.4 (P = 0.981) respectively. Approximately 45%
      of subjects in PCOS group remained anovulatory in spite of decreased level of LH
      and testosterone. Prolactin level remained elevated in 73.2% of women who did not
      ovulate 6-10 weeks after the procedure. CONCLUSION: Hyperprolactinemia after
      ovarian cauterization may be considered as a possible cause of anovulation in
      women with polycystic ovaries and improved gonadotropin and androgen levels. The
      cause of hyperprolactinemia is unknown. Hormonal assay particularly PRL in
      anovulatory patients after ovarian cauterization is recommended.

PMID- 16083512
TI  - Usefulness of five-item and three-item Mental Health Inventories to screen for
      depressive symptoms in the general population of Japan.
AB  - BACKGROUND: The five-question Mental Health Inventory (MHI-5) is a brief
      questionnaire that can be used to screen for depressive symptoms. Removing the 2
      anxiety-related items from the MHI-5 yields the MHI-3. We assessed the
      performance of the Japanese versions of the MHI-5 and MHI-3 in detecting
      depressive symptoms in the general population of Japan. METHODS: From the
      population of Japan, 4500 people 16 years old or older were selected by
      stratified-random sampling. The Medical Outcomes Study 36-Item Short Form Health
      Survey (SF-36, which includes the MHI-5) and the Zung Self-rating Depression
      Scale (ZSDS) were included in a self-administered questionnaire. ZSDS scores of
      48 and above were taken to indicate the presence of moderate or severe depressive
      symptoms, and scores of 56 and above were taken to indicate the presence of
      severe depressive symptoms. We computed the correlation coefficient between the
      ZSDS score and the scores on the MHI-5 and MHI-3. We also computed the
      sensitivity, specificity, and area under the receiver operating characteristic
      (ROC) curve. RESULTS: Of the 3107 subjects (69% of the 4500 initially selected),
      14.0% had moderate or severe depressive symptoms, and 2.0% had severe depressive
      symptoms as measured with the ZSDS. The correlations of ZSDS scores with MHI-5
      scores and with MHI-3 scores were similar: -0.63 and -0.61, respectively. These
      correlation coefficients were almost the same whether or not the data were
      stratified by age and sex. For detecting severe depressive symptoms with the MHI
      5, the area under the ROC curve was 0.942 (95%CI: 0.919 - 0.965); for the MHI-3,
      it was 0.933 (95%CI: 0.904 - 0.962). CONCLUSION: The MHI-5 and MHI-3 scores were
      correlated with the ZSDS score, and can be used to identify people with
      depressive symptoms in the general population of Japan.

PMID- 16083513
TI  - CareSearch: finding and evaluating Australia's missing palliative care
      literature.
AB  - BACKGROUND: Palliative care is an evolving specialty with a growing evidence
      base. However, evidence is less accessible than it could be with a lower than
      average conversion of conference abstracts to articles in peer-reviewed journals
      and the need for more accessible tools to support evidence-based practice (EBP)
      in palliative care. The CareSearch project involved identifying, collecting and
      evaluating Australia's "grey" palliative care literature and identifying
      international published literature missing from the electronic indexing systems.
      The literature was then catalogued and made publicly available through the
      CareSearch website. RESULTS: To date over 2,500 items have been included in the
      CareSearch database and can be accessed and searched through a publicly available
      website. Nearly 2,000 items are conference abstracts and 178 are theses or
      government, organisational and planning documents. A further 410 items relate to
      articles from palliative journals that are not indexed on a major bibliographic
      database. The website also provides tools and facilities to support palliative
      care practice and research. CONCLUSION: CareSearch is a new evidence resource for
      palliative practitioners, educators and researchers. The palliative community now
      has access to a more comprehensive literature base as well as a resource that
      supports the integration of knowledge into practice. This specialised data
      repository enables users to access information on the body of work that has
      shaped palliative care development and prevents the potential loss or duplication
      of research work. It also provides a template for other emerging disciplines to
      use in capturing their literature and evidence.

PMID- 16083514
TI  - Global expression profiling of theophylline response genes in macrophages:
      evidence of airway anti-inflammatory regulation.
AB  - BACKGROUND: Theophylline has been used widely as a bronchodilator for the
      treatment of bronchial asthma and has been suggested to modulate immune response.
      While the importance of macrophages in asthma has been reappraised and
      emphasized, their significance has not been well investigated. We conducted a
      genome-wide profiling of the gene expressions of macrophages in response to
      theophylline. METHODS: Microarray technology was used to profile the gene
      expression patterns of macrophages modulated by theophylline. Northern blot and
      real-time quantitative RT-PCR were also used to validate the microarray data,
      while Western blot and ELISA were used to measure the levels of IL-13 and LTC4.
      RESULTS: We identified dozens of genes in macrophages that were dose-dependently
      down- or up-regulated by theophylline. These included genes related to
      inflammation, cytokines, signaling transduction, cell adhesion and motility, cell
      cycle regulators, and metabolism. We observed that IL-13, a central mediator of
      airway inflammation, was dramatically suppressed by theophylline. Real-time
      quantitative RT-PCR and ELISA analyses also confirmed these results, without
      respect to PMA-treated THP-1 cells or isolated human alveolar macrophages.
      Theophylline, rolipram, etazolate, db-cAMP and forskolin suppressed both IL-13
      mRNA expression (~25%, 2.73%, 8.12%, 5.28%, and 18.41%, respectively) and protein
      secretion (<10% production) in macrophages. These agents also effectively
      suppressed LTC4 expression. CONCLUSION: Our results suggest that the suppression
      of IL-13 by theophylline may be through cAMP mediation and may decrease LTC4
      production. This study supports the role of theophylline as a signal regulator of
      inflammation, and that down regulation of IL-13 by theophylline may have
      beneficial effects in inflammatory airway diseases.

PMID- 16083515
TI  - Targeting acetylcholinesterase and butyrylcholinesterase in dementia.
AB  - The cholinesterase inhibitors (ChE-Is) attenuate the cholinergic deficit
      underlying the cognitive and neuropsychiatric dysfunctions in patients with AD.
      Inhibition of brain acetylcholinesterase (AChE) has been the major therapeutic
      target of ChE-I treatment strategies for Alzheimer's disease (AD). AChE-positive
      neurons project diffusely to the cortex, modulating cortical processing and
      responses to new and relevant stimuli. Butyrylcholinesterase (BuChE)-positive
      neurons project specifically to the frontal cortex, and may have roles in
      attention, executive function, emotional memory and behaviour. Furthermore, BuChE
      activity progressively increases as the severity of dementia advances, while AChE
      activity declines. Therefore, inhibition of BuChE may provide additional
      benefits. The two cholinesterase (ChE) enzymes that metabolize acetylcholine
      (ACh) differ significantly in substrate specificity, enzyme kinetics, expression
      and activity in different brain regions, and complexity of gene regulation. In
      addition, recent evidence suggests that AChE and BuChE may have roles beyond
      'classical' co-regulatory esterase functions in terminating ACh-mediated
      neurotransmission. 'Non-classical' roles in modulating the activity of other
      proteins, regional cerebral blood flow, tau phosphorylation, and the amyloid
      cascade may affect rates of AD progression. If these additional mechanisms are
      demonstrated to underlie clinically meaningful effects, modification of the over
      simplistic cholinergic hypothesis in AD that is limited to symptomatic treatment,
      ignoring the potential of cholinergic therapies to modify the disease process,
      may be appropriate. The specificity of ChE inhibitory activity, up-regulation of
      AChE activity and changes in the composition of AChE molecular forms over time,
      selectivity for AD-relevant ChE molecular forms, brain vs. peripheral
      selectivity, and pharmacokinetic profile may be important determinants of the
      acute and long-term efficacy, safety and tolerability profiles of the different
      ChE-Is. This review focuses on new evidence for the roles of BuChE and AChE in
      symptom generation and rate of underlying disease progression in dementia, and
      argues that it may be appropriate to re-evaluate the place of ChE-Is in the
      treatment of dementia.

PMID- 16083517
TI  - Part I: what do patients really need and want from migraine treatment?
AB  - Migraine is characterised by recurrent episodes of head pain, often accompanied
      by other symptoms, such as nausea and vomiting. In addition to migraine impairing
      a patient's ability to function normally during an attack, fear of the next
      attack can detract from quality of life between attacks. Of those migraineurs who
      consult a physician for headache, the minority are prescribed migraine-specific
      triptans and many are dissatisfied with current therapy. Clinical trials have
      shown that triptans are capable of providing rapid and effective relief of
      headache pain, which is what patients primarily desire from acute migraine
      therapies. Patients generally prefer to administer acute migraine therapies
      orally, but conventional tablets do not suit all patients and situations. Some
      patients dislike swallowing tablets, nausea can make swallowing difficult and can
      be exacerbated by fluid intake, and attacks can easily strike when fluids are not
      readily available, especially as many young migraineurs lead busy, active lives.
      Patients need a treatment that enables any migraine attack to be treated promptly
      and effectively in any given situation. Tablets that dissolve rapidly on the
      tongue without a requirement for extra fluid intake are a popular alternative to
      conventional tablets, allowing discreet, convenient and early treatment of
      migraine anywhere and anytime it strikes. Several triptans are currently on the
      market in conventional tablet form, but some are available in other formulations,
      such as orally disintegrating tablets or nasal sprays, making it possible to
      prescribe rapidly effective migraine treatments in formulations that suit
      individual patient preferences, lifestyles and attack characteristics.

PMID- 16083518
TI  - Part II: clinical efficacy and tolerability of zolmitriptan orally disintegrating
      tablet in the acute treatment of migraine.
AB  - Controlled clinical trials and extensive clinical use of conventional oral
      tablets of zolmitriptan, a selective agonist of serotonin1B/1D receptors, have
      proven the compound to be fast-acting, highly effective, and well-tolerated in
      the acute treatment of migraine. An orally disintegrating tablet (ODT) of
      zolmitriptan that dissolves on the tongue without the need for fluid intake has
      been developed in order to provide an acceptable, convenient alternative for
      patients who prefer not to, or cannot, take conventional tablets. A fast onset of
      effective, sustained pain relief was predicted for zolmitriptan ODT on the basis
      of its bioequivalence with the conventional tablet, which has been confirmed in
      three randomised, double-blind, placebo-controlled trials of zolmitriptan ODT in
      the acute treatment of migraine. Compared with placebo, significantly higher
      proportions of patients treated with zolmitriptan ODT responded to treatment
      (reduction of moderate or severe headache to mild or no pain) as early as 30
      minutes after dosing. Headache response was maintained at 24 hours in
      significantly higher proportions of patients receiving zolmitriptan ODT compared
      with placebo. Zolmitriptan ODT also resulted in significantly greater pain-free
      rates than placebo as early as 1 hour after dosing. Zolmitriptan ODT relieved
      patients of other migraine-associated symptoms, including nausea, photophobia and
      phonophobia, and enabled >50% of patients to resume normal daily activities 2
      hours after dosing. Adverse events observed with zolmitriptan ODT were similar to
      those associated with the serotonin1B/1D agonists as a class, and were generally
      transient and of mild or moderate intensity.

PMID- 16083519
TI  - Part III: the convenience of, and patient preference for, zolmitriptan orally
      disintegrating tablet.
AB  - As part of an optimal strategy for the management of migraine, the individual
      needs and preferences of patients need to be considered when of patients need to
      be considered when prescribing treatments. Zolmitriptan has been available as a
      conventional oral tablet for more than seven years, and is established as a
      highly effective, well-tolerated compound for the acute treatment of migraine. A
      bioequivalent, orally disintegrating tablet (ODT) of zolmitriptan, which
      dissolves on the tongue without the need for additional fluid intake, has been
      developed. In a study designed to compare patient preference for zolmitriptan ODT
      and conventional oral sumatriptan tablets, > 60% of the 186 patients questioned
      had an overall preference for zolmitriptan ODT, with > 80% of patients reporting
      that this was the more convenient and less disruptive therapy to take.
      Approximately 90% of patients agreed that, unlike a conventional tablet,
      zolmitriptan ODT can be taken wherever and whenever a migraine occurs. When
      patient preference for zolmitriptan ODT and the ODT formulation of rizatriptan
      was compared in 171 migraineurs, 70% had an overall preference for zolmitriptan
      ODT to be superior to rizatriptan ODT with respect to taste and aftertaste, as
      well as packaging. In summary, not only is zolmitriptan ODT a convenient tablets,
      such as the sumatriptan oral tablet, but patients generally consider it to be a
      more attractive option for the acute treatment of migraine than the orally
      disintegrating version of rizatriptan.

PMID- 16083520
TI  - Part IV: effects of zolmitriptan orally disintegrating tablet on migraine
      symptoms and ability to perform normal activities: a post-marketing surveillance
      study in Germany.
AB  - Zolmitriptan has been developed in an orally disintegrating tablet (ODT)
      formulation that rapidly dissolves on the tongue and can be taken quickly,
      conveniently and discreetly without fluid intake. In this 3-month, non
      comparative, observational, post-marketing surveillance (PMS) study, 5,570
      physicians prescribed the zolmitriptan 2.5 mg ODT for 16,261 patients with
      migraine. Of the 14,543 patients who were evaluable for efficacy analysis, 94%
      had reduced headache intensity within 2 hours of taking zolmitriptan 2.5 mg ODT
      for the first attack. Improvements were reported within 30 minutes in 35% of
      patients and within 15 minutes in 7% of patients. Non-headache migraine symptoms
      and normal daily activities improved for the majority of patients within 2 hours
      of taking zolmitriptan ODT. Ninety-one percent of patients required only a single
      dose of zolmitriptan 2.5 mg ODT to treat each attack. Ninety-two percent of
      patients considered zolmitriptan ODT as having very good or good efficacy and 96%
      said that tolerability was very good or good. This study also demonstrated that
      94% of patients would be willing to continue to use zolmitriptan ODT in the
      future and 81% of patients considered that being able to take the ODT without
      water was important or very import ant. In summary, zolmitriptan ODT has
      demonstrated high efficacy and excellent tolerability. In addition, patients
      found zolmitriptan ODT to be convenient and easy to use, and were willing to
      continue using the product. Following placebo-controlled studies, these PMS
      results provide insight into the use of zolmitriptan ODT in a setting more
      representative of real life than randomised clinical trials, further
      demonstrating that it provides a reliable and convenient alternative to
      conventional tablets.

PMID- 16083521
TI  - A comparative, randomised, double-blind study of trazodone prolonged-release and
      paroxetine in the treatment of patients with major depressive disorder.
AB  - OBJECTIVES: To evaluate the efficacy and safety of trazodone prolonged release
      compared with paroxetine in the treatment of patients with major depression.
      RESEARCH DESIGN AND METHODS: A total of 108 patients aged 20-68 years were
      enrolled in this multicentre, double-blind, double-dummy, randomised, paroxetine
      controlled study. Each patient received 3 days single-blind placebo treatment
      followed by 6 weeks double-blind treatment with either trazodone prolonged
      release 150-450 mg/day (n = 55) or paroxetine 20-40 mg/day (n = 53). OUTCOME
      MEASURES: Efficacy was evaluated by the rate of patients responding to each
      treatment and considered to be in remission, and by mean changes from baseline in
      the Hamilton Depression Rating scale scores (HAM-D), Montgomery Asberg Depression
      Rating Scale scores (MADRS), and Clinical Global Impression (CGI)--Severity and
      Global Improvement scores. Time to onset of efficacy and safety were assessed.
      RESULTS: Trazodone and paroxetine were equally effective at reducing symptoms of
      depression and promoting remission. Onset of efficacy was slightly faster for
      patients treated with paroxetine. Overall, there were no significant differences
      between the groups at endpoint in efficacy measures, and in percentage of
      responders (> 85%) or patients in remission (> 65%). Sleep disorders (HAM-D
      subset) were significantly less evident for patients in the trazodone group at
      the end of the study (p < 0.05). Adverse drug reactions were reported by 35% of
      trazodone-treated patients (mainly of the nervous system) and 26% of paroxetine
      treated patients (mainly gastrointestinal), although none was considered to be
      serious. CONCLUSIONS: This study showed that after a 6-week period trazodone and
      paroxetine are not different in reducing the symptoms of depression and, in many
      patients, in producing the remission of the illness. The known divergence in
      tolerability profile of the two medications, related to their differing
      pharmacological properties, was also confirmed. Trazodone may be of advantage in
      depressed patients with sleep difficulties.

PMID- 16083522
TI  - Transdermal buprenorphine in clinical practice--a post-marketing surveillance
      study in 13,179 patients.
AB  - OBJECTIVE: The objective of this post-marketing surveillance study was to collect
      effectiveness and safety data on the labelled use of buprenorphine transdermal
      patches (Transtec*) under routine clinical conditions. RESEARCH DESIGN AND
      METHODS: For this open, observational study, patients with moderate to severe
      cancer or non-cancer pain requiring treatment with an opioid analgesic were
      recruited at hospitals, outpatient clinics and general practitioners' practices
      in Germany. Buprenorphine transdermal patches (35 microg/h, 52.5 microg/h or 70
      microg/h) were prescribed at physicians' discretion in accordance with the
      product's Summary of Product Characteristics (SmPC). Patients assessed their pain
      relief as 'very good', 'good', 'satisfactory', 'poor' or 'no effect'.
      Investigators were instructed to report all adverse events throughout the
      observation period. On completion, effectiveness and tolerability were evaluated
      for the overall study population, cancer and non-cancer patients, and patients <
      70 years and > or = 70 years. Other analyses assessed pain relief with respect to
      previous opioid treatment and increased patch strength, and in patients who
      remained on their original dose. The total observation time was 9 months, and the
      average individual documented treatment time was 60.8 days. RESULTS: A total of
      13,179 patients were evaluated; 3690 (28%) with cancer pain and 9489 (72%) with
      non-cancer pain. The most frequent diagnoses in non-cancer patients were
      musculoskeletal disorders (77%) and neuropathy (23%). In the great majority of
      cases (78%), treatment was started with the 35 microg/h patch. The initial dose
      needed to be increased subsequently only in about 18% of subjects. Buprenorphine
      transdermal patches provided effective, sustained and dose-dependent analgesia in
      patients with cancer and non-cancer pain, irrespective of the patients' age or
      pain syndromes. Whereas good or very good pain relief was documented only for 6%
      of the patients with the initial assessment, this percentage increased to 71% at
      the first follow-up and 80% at the final assessment. Fewer than 5% of subjects
      discontinued treatment owing to unsatisfactory pain relief. Altogether, adverse
      events were documented for 2874 patients (22%), whereas a relationship with trans
      dermal buprenorphine (adverse drug reactions) was assumed for only 10% (2220
      adverse drug reactions in 1330 patients). The tolerability profile was as
      expected for an opioid and did not vary to a relevant extent with either the
      patient's age or the cause of pain (cancer or non-cancer). No evidence emerged of
      any previously unknown side effects. CONCLUSIONS: Buprenorphine transdermal
      patches are well tolerated and effective in the treatment of chronic cancer and
      non-cancer pain, irrespective of the patients' age. There was no clinically
      relevant development of tolerance.

PMID- 16083523
TI  - The prevalence of the metabolic syndrome using the National Cholesterol
      Educational Program and International Diabetes Federation definitions.
AB  - OBJECTIVE: The prevalence of metabolic syndrome (MetS), using the National
      Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and
      International Diabetes Federation (IDF) definitions, was compared in 9669
      subjects, representing the Greek population. RESULTS: The age-adjusted prevalence
      of NCEP ATP III-defined MetS was 24.5% whereas that of IDF-defined MetS was 43.4%
      (+77%,p < 0.0001). The majority (up to 69%) of older age groups had IDF-defined
      MetS. The calculated vascular event risk was low (6.1% and 7.2% using the
      Framingham and PROCAM calculation, respectively) in those with IDF-defined MetS
      when compared with those with NCEP ATP III MetS (11.3% and 13.7%, respectively)
      (p < 0.0001 for both comparisons). CONCLUSION: MetS could be considered as a
      'normal' variant if it was present in the majority of the population. Moreover,
      the vascular risk associated with IDF-defined MetS could be low, raising cost
      effectiveness issues. Alternatively, the new IDF definition may realistically
      reflect the current MetS epidemic. More studies are required to support or refute
      those interpretations.

PMID- 16083524
TI  - Renal protection by radical scavenging in cardiac surgery patients.
AB  - OBJECTIVE: Renal function impairment is a common complication in cardiac surgery
      patients. Because cardiopulmonary bypass and cardioplegic arrest are associated
      with formation of free radicals, which have been shown to impair various organs
      including the kidneys, radical scavenging may protect renal function. Therefore,
      the purpose of our study was to evaluate the impact of the radical scavenger N
      acetylcysteine (NAC) versus placebo on peri-operative renal function in cardiac
      surgery patients. RESEARCH DESIGN AND METHODS: We reanalyzed the data of our
      previous study in which 40 coronary artery surgery patients (66 +/- 9 [SD] years,
      9 women and 31 men) with normal pre-operative renal function had been randomized
      in a double-blind fashion to receive either NAC (100 mg/kg into the
      cardiopulmonary bypass prime followed by infusion at 20 mg/kg/h; n = 20) or
      placebo (n = 20). We determined serum creatinine levels as an indicator for renal
      function pre- and at 1 day post-surgery as well as peri-operative urinary output
      and diuretic medication. Creatinine clearance was calculated according to
      Cockcroft and Gault. RESULTS: Biometric and intra-operative patient data were
      similar between both groups. In the placebo group, serum creatinine increased
      from 93.1 +/- 35.4 micromol/L pre-operatively to 115.9 +/- 47.2 micromol/L on
      post-op day 1 (p < 0.001). In contrast, serum creatinine in the NAC group
      remained unchanged (92.3 +/- 31.3 micromol/L pre-op; 99.3 +/- 25.4 micromol/L on
      post-op day 1; p = 0.084). Accordingly, creatinine clearance decreased by 16.9 +/
      14.3 mL/min in the placebo group as compared to 7.5 +/- 17.7 mL/min in the NAC
      group (p = 0.039). Urinary output and diuretic medication were similar between
      NAC and placebo. CONCLUSIONS: Our data suggest that free radical-scavenging using
      NAC protects renal function in patients subjected to cardiac surgery on
      cardiopulmonary bypass.

PMID- 16083525
TI  - An open-label evaluation of rifaximin in the treatment of active Crohn's disease.
AB  - OBJECTIVE: This open-label study was conducted as a preliminary assessment of
      rifaximin (200 mg TID for 16 weeks) for the treatment of active Crohn's disease
      in patients (n = 29) with symptoms for at least 3 months before screening and a
      Crohn's Disease Activity Index (CDAI) score > 220 and < 400. RESULTS: At the end
      of month 4, mean +/- CDAI score was reduced by 43% compared with baseline in the
      intent-to-treat population (n = 29; baseline = 278 +/- 51; month 4 = 159 +/- 102;
      p < 0.0001 month 4 versus baseline). A similar pattern of results was observed in
      the per-protocol population (i.e., patients at least 70% compliant with the
      treatment regimen and having no protocol violations thought to affect efficacy
      results; n = 16), in which mean CDAI scores at month 4 were reduced by 41% from a
      baseline of 262.9 +/- 38.2 to 155.6 +/- 104.5 (p = 0.0009 month 4 versus
      baseline). Fifty-nine percent of patients (59%) had a > or = 70-point improvement
      in CDAI score beginning with the first assessment at the end of month 1. By the
      end of the treatment period, 78% of patients had a > or = 70-point improvement in
      CDAI score. Clinical remission, defined as CDAI score < 150, was observed at the
      end of treatment months 1, 2, 3, and 4 in 41%, 56%, 56%, and 59% of patients,
      respectively. Twenty-three (23) patients completed the 4-month course of
      rifaximin therapy, and 6 prematurely withdrew. The most common adverse events
      were abdominal pain, fatigue, and headache. CONCLUSION: These data, which are
      consistent with the possibility that rifaximin may be useful for active Crohn's
      disease, warrant confirmation in a randomized, double-blind, placebo-controlled
      trial.

PMID- 16083526
TI  - The effect of fluvastatin on the pharmacokinetics and pharmacodynamics of
      ezetimibe.
AB  - OBJECTIVE: The objective of this study was to evaluate the pharmacodynamic
      effects and safety of the co-administration of ezetimibe and fluvastatin in
      healthy hypercholesterolemic subjects at clinically-relevant doses and to
      evaluate the potential for a pharmacokinetic drug interaction between ezetimibe
      and fluvastatin. METHODS: In a single-center, evaluator-blind, placebo
      controlled, multiple-dose, parallel-group study 32 healthy subjects with
      hypercholesterolemia were randomized to 4 treatments administered once daily for
      14 days: ezetimibe 10 mg plus ezetimibe placebo, fluvastatin 20 mg plus ezetimibe
      placebo, fluvastatin 20 mg plus ezetimibe 10 mg, and ezetimibe placebo. Blood
      samples were collected to measure serum lipids and to determine steady-state
      pharmacokinetics. RESULTS: Ezetimibe 10 mg significantly (p < or = 0.01)
      decreased total-cholesterol and low-density lipoprotein cholesterol (LDL-C)
      concentrations compared to placebo at Day 14. Fluvastatin 20 mg also caused a
      significant (p = 0.01) reduction in total-cholesterol and a decrease in LDL-C at
      Day 14 compared to placebo, however, the decrease in LDL-C did not reach
      statistical significance (p = 0.08). The coadministration of ezetimibe 10 mg and
      fluvastatin 20 mg caused significantly (p < or = 0.01) greater mean percent
      reductions in LDL-C and total-cholesterol than fluvastatin 20 mg alone or placebo
      at Day 14. Fluvastatin had no clinically significant effect on the
      pharmacokinetics of ezetimibe. On average, ezetimibe appeared to decrease the
      rate and extent of fluvastatin bioavailability. CONCLUSION: Coadministration of
      ezetimibe and fluvastatin was safe and well tolerated and caused significant
      incremental reductions in LDL-C and total cholesterol compared to fluvastatin
      administered alone. The pharmacokinetics of ezetimibe were not affected by
      coadministration with fluvastatin. The apparent decrease in fluvastatin exposure
      on administration with ezetimibe was likely to be due to the parallel study
      design and two pharmacokinetic outliers and is considered of no clinical
      significance.

PMID- 16083527
TI  - Methotrexate dosage reduction in patients with rheumatoid arthritis beginning
      therapy with infliximab: the Infliximab Rheumatoid Arthritis Methotrexate
      Tapering (iRAMT) trial.
AB  - OBJECTIVE: Infliximab plus methotrexate (MTX) is approved for the treatment of
      rheumatoid arthritis (RA). Based on the benefit/risk profile of this combination
      therapy, lower doses of MTX would be preferable when infliximab efficacy can be
      maintained. We evaluated the ability of patients receiving infliximab plus MTX to
      achieve and maintain a clinical response while the dose of MTX was tapered.
      METHODS: Infliximab infusions were administered at a minimum dosage of 3 mg/kg at
      8-week intervals (following three loading doses at weeks 0, 2, and 6) to patients
      who had an inadequate response to MTX. MTX tapering was initiated at week 22 or
      later when at least a 40% improvement in the combined tender and swollen joint
      count was achieved; dosages were reduced by 5 mg every 8 weeks to a protocol
      specified minimum dosage of 5 mg per week. If the required dosage of MTX after a
      flare was greater than the baseline dosage, the patient was considered a
      treatment failure. RESULTS: Of the 210 patients enrolled, 159 (76%) achieved a
      40% or better improvement in the combined tender and swollen joint count and had
      their MTX doses tapered. In these 159 responders, the median (mean) dose of MTX
      was reduced from 15 (16.5) mg per week at baseline to 5 (7.1) mg per week at week
      54. From the time of initial response, 79% of these patients had a zero- or a one
      vial increase in infliximab, corresponding to an approximate dose increase of 1
      mg/kg, through week 54. CONCLUSION: Approximately 75% of the patients
      participating in this trial achieved at least a 40% reduction in the combined
      swollen and tender joint count (correlating with an American College of
      Rheumatology 20% [ACR20] response in 83% of patients) while reducing the mean MTX
      dose by 57%.

PMID- 16083528
TI  - Optimizing treatment of diabetes and cardiovascular disease with combined
      alpha,beta-blockade.
AB  - BACKGROUND: Cardiovascular risk factors of the diabetic patient should be treated
      as aggressively as those of the nondiabetic patient who has had a myocardial
      infarction. beta-Blockers are established to reduce cardiovascular risk in
      patients with hypertension, coronary heart disease, and heart failure. Despite
      this benefit of beta-blockers, physicians have been reluctant to use them in
      patients with diabetes, in whom they are even more effective, because of the
      negative effects on carbohydrate and lipid metabolism. OBJECTIVE: This paper
      reviews (based on a Medline literature search to December 2004) the relationship
      between diabetes and cardiovascular risk factors, describes the metabolic
      consequences of insulin resistance, and discusses the impact of different beta
      blockers on the treatment of cardiovascular disease in patients with diabetes.
      RESULTS: There is a large cardioprotective benefit with the use of beta-blockers
      in patients with diabetes; however, metabolic risks are associated with some beta
      blockers. Newer, vasodilating, nonselective beta-blockers do not have the same
      adverse metabolic consequences observed with earlier beta-blockers. Recent
      evidence has shown that they have a neutral effect on metabolic parameters and
      lipid profile. They do not promote insulin resistance and can be used safely in
      heart failure patients with diabetes. CONCLUSIONS: Nonselective vasodilating beta
      blockers, such as carvedilol, may be used in patients with cardiovascular disease
      and diabetes without the same negative metabolic consequences seen with the use
      of earlier generation beta-blockers.

PMID- 16083529
TI  - Impaired renal function and atherosclerosis in a Pakistani cohort.
AB  - OBJECTIVE: To investigate the relationship of creatinine and calculated
      glomerular filtration rate (GFR) with coronary arterial disease (CAD) in
      Pakistani patients. SUBJECTS: Four hundred individuals with chest pain; 200 with
      angiographic disease matched with 200 without occlusive disease. DESIGN: A
      prospective case-control study. SETTING: A tertiary referral cardiology unit in
      Pakistan. RESULTS: Impaired renal function as estimated by calculated GFR was
      common in this population. Creatinine and glomerular filtration rate, as
      calculated by the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease
      (MDRD) formulae, were associated with CAD and atherosclerotic burden in Pakistani
      patients. Calculation of creatinine clearance, correcting for age, sex and body
      mass index, showed that clearance was 81 (17-257) mL/min/1.73 m2 in patients with
      CAD compared with 88 (23-167) mL/min/1.73 m2 in controls with a significant
      number of patients (18.5 vs. 6.5%; RR = 2.85; p < 0.001) showing significant
      renal impairment (< 60 mL/min/1.73 m2) by CG and more by the MDRD equation (26
      vs. 9%; RR = 2.88; p < 0.001). The unadjusted odds ratios for CAD for a GFR < 60
      mL/min/1.73 m2 were 3.66 (1.87-7.16) and 3.29 (1.81-6.01), respectively and,
      after adjustment for diabetes, smoking, insulin resistance, inflammation and
      apolipoprotein A1, 1.04 (1.02-1.09) and 1.04 (1.02-1.09), respectively.
      CONCLUSIONS: Impaired renal function is common in Pakistani patients with
      coronary arterial disease and is strongly associated with a risk of
      atherosclerosis independent of insulin resistance.

PMID- 16083530
TI  - Validation of the EQ-5D in patients with a history of acute coronary syndrome.
AB  - OBJECTIVE: To analyze the construct validity of the EQ-5D in patients with acute
      coronary syndromes (ACS). METHODS: All ACS-diagnosed patients discharged from a
      university-affiliated hospital during a 3-year period were mailed a questionnaire
      that included the EQ-5D and the SF-8. The EQ-5D includes a visual analogue scale
      (EQ VAS) to measure self-reported current health-status (0-100) and a five-item
      descriptive system measuring mobility, self-care, usual activities,
      pain/discomfort, and anxiety/depression. Also included were disease severity
      measures [Duke Activity Status Index (DASI), cardiac symptom count (SC), patient
      perceived cardiac disease severity], comorbidity measures (Charlson comorbidity
      index, total medication count), and other demographic and disease-related items.
      RESULTS: Of 1217 patients, 490 (40.3%) responded. Patients averaged 65.2 (SD
      11.3) years of age; 71.0% male; 91.9% Caucasian; 64.3% history of MI. Only 0.2%
      0.4% of EQ-5D items and 8% of the EQ VAS were left unanswered by respondents. The
      nine most common health states were identified based on the five EQ-5D item
      scores. Levels of responses to EQ-5D items and the EQ VAS score were
      significantly better for patients with very mild/mild perceived disease severity
      compared to severe/very severe, for patients with lower comorbidity, for patients
      with lower symptom responses, and for patients with a higher cardiac-related
      functioning. EQ VAS score and SF-8 subscale score correlation coefficients ranged
      from 0.527 to 0.798 (all p < 0.0001). Significant differences were observed
      between the response level of individual EQ-5D items and scores of comparable SF
      8 subscales. CONCLUSIONS: This study demonstrated the construct validity of the
      EQ-5D in a population-based sample of patients with a history of ACS.

PMID- 16083531
TI  - Update on cyclooxygenase inhibitors: has a third COX isoform entered the fray?
AB  - It has been more than 30 years since Sir John Vane first reported that the
      pharmacological actions of aspirin-like drugs could be explained by their ability
      to inhibit cyclooxygenase (COX). Since then, a second isoform of COX, named COX
      2, has been discovered and highly selective inhibitors of this isoform have been
      marketed. Most recently, a splice variant of COX-1 mRNA, retaining intron 1, and
      given the names COX-3, COX-1b or COX-1v, has been described. Non-selective NSAIDs
      such as ibuprofen and naproxen, which inhibit both COX-1 and COX-2, have proven
      highly effective and safe in the short-term management of acute pain. Highly
      selective COX-2 inhibitors including celecoxib, rofecoxib, valdecoxib,
      lumiracoxib, and etoricoxib were developed with the hope of significantly
      reducing the serious gastrointestinal toxicities associated with chronic high
      dose NSAID use. While long-term studies demonstrated that rofecoxib and
      lumiracoxib reduced the incidence of GI perforations, ulcerations and bleeds by
      approximately 60% compared to non-selective NSAIDs, recent reports also
      demonstrated that the chronic use of rofecoxib and celecoxib in arthritis and
      colorectal polyp patients, and the short-term use of parecoxib and valdecoxib in
      patients who had undergone coronary artery bypass surgery, resulted in a
      significant increase in serious cardiovascular events, including myocardial
      infarction and stroke compared to naproxen or placebo. COX-3 mRNA has been
      isolated in many tissues including canine and human cerebral cortex, human aorta,
      and rodent cerebral endothelium, heart, kidney and neuronal tissues. In
      transfected insect cells, canine COX-3 protein is expressed and was selectively
      inhibited by acetaminophen. However, in humans and rodents an acetaminophen
      sensitive COX-3 protein is not expressed because the retention of intron-1 adds
      94 and 98 nucleotides to the COX-3 mRNA structure respectively. Since the genetic
      code is a triplicate code (3 nucleotides to form one amino acid), the retention
      of the intron in both species results in a frame shift in the RNA message and the
      production of a truncated protein with a completely different amino acid sequence
      than COX-1 or COX-2 lacking acetaminophen sensitivity. Advances made through a
      combination of basic molecular biological and pharmacological techniques, and
      well designed randomized controlled clinical trials have demonstrated that the
      apparent gastrointestinal advantage of selective COX-2 inhibitors appears to be
      outweighed by their potential for cardiovascular toxicity and that
      acetaminophen's analgesic and antipyretic effects do not involve the inhibition
      of the COX-1 splice variant protein, putative COX-3.

PMID- 16083532
TI  - Guidance for the management of hirsutism.
AB  - Approximately 80% of women are affected by the presence of excessive hair growth
      in a 'male-like' pattern. Excessive facial hair in particular can be a source of
      distress to such women and can lead to psychological problems such as anxiety,
      depression and a reduced quality of life.Current cosmetic methods of hair removal
      include shaving, depilatories, waxing, plucking, laser, intense pulsed light
      (IPL) and electrolysis.A topical treatment cream such as eflornithine 11.5% can
      slow hair growth and thus reduce the frequency of the need for hair removal. This
      treatment can be used effectively in conjunction with hair removal methods.

PMID- 16083533
TI  - Second-degree burns: a comparative, multicenter, randomized trial of hyaluronic
      acid plus silver sulfadiazine vs. silver sulfadiazine alone.
AB  - AIMS: This multicenter, multinational, randomized, double-blind, controlled,
      parallel-group study, was designed to assess the efficacy and safety of a fixed
      combination topical medicinal product, containing 0.2% hyaluronic acid and 1%
      silver sulfadiazine (HA-SSD) (Connettivina Plus cream) versus 1% silver
      sulfadiazine cream alone (SSD), in the treatment of second-degree burns. METHODS:
      111 adult patients (age 18-75 years) of both sexes, with IIa-degree (superficial)
      and IIb-degree (deep dermal) burns, were randomized to receive HA-SSD or SSD.
      Treatments (approximately 5 g/100 cm2) were applied once a day until the wounds
      healed, but for no longer than 4 weeks. Burns had to have occurred within 48
      hours from the start of treatment, be caused by thermal injury, and be confined
      to the trunk and/or upper and lower extremities. RESULTS: Results showed that
      both the fixed combination HA-SSD, and SSD alone, were effective and well
      tolerated topical agents for the treatment of second-degree burns. All burns were
      healed except in one patient treated with SSD. It was also observed that the
      fixed combination HA-SSD caused a significantly more rapid re-epithelialization
      of burns, i.e. a shorter time to healing, than SSD alone. The difference recorded
      -4.5 days--was statistically significant (p = 0.0073). CONCLUSION: The observed
      shorter time to healing caused by the fixed combination is clinically relevant
      and further demonstrates the wound healing activity of HA.

PMID- 16083534
TI  - Time to symptom relief for uncomplicated urinary tract infection treated with
      extended-release ciprofloxacin: a prospective, open-label, uncontrolled primary
      care study.
AB  - OBJECTIVE: Few studies have investigated symptom relief in urinary tract
      infections. This innovative exploratory trial aimed to measure the time to
      improvement of the signs and symptoms of uncomplicated urinary tract infection
      (UTI) in women receiving extended-release ciprofloxacin. Time to return to normal
      daily activities was also evaluated. RESEARCH DESIGN AND METHODS: An open-label,
      multicenter US study in adult female outpatients with uncomplicated UTI. Patients
      completed serial questionnaires: the Urinary tract infection Symptom Assessment
      [USA], tracking time to symptom improvement, and the Activity Impairment
      Assessment [AIA], measuring the time to return to normal daily activities, using
      hand-held electronic diaries. Severity on the USA questionnaire was categorized
      using a 4-point Likert-type scale, with improvement defined as a reduction of at
      least one degree of symptom severity. All patients received once-daily extended
      release ciprofloxacin 500 mg tablets for 3 days. RESULTS: Of 276 female patients
      aged 18-78 years who enrolled at 28 sites, 273 (99%) were safety-valid, 264 (96%)
      completed at least 24 h of questionnaires and were valid for symptom relief
      analysis, and 170 (62%) had pre-therapy pathogen(s) > or = 10(3) CFU/mL and were
      valid for efficacy analysis. Six hours after the first dose of study drug, 50% of
      patients reported symptom improvement; 87% by 24 h and 91% by 48 h. At study
      entry, 54% of patients reported considerably decreased time at work or other
      activities; reduced to 23% by Day 2 and 10% by Day 3. At the test-of-cure visit
      (5-11 days post-therapy), 96% (163/170) of patients were clinical cures. Drug
      related adverse events were reported by 18 (7%) patients and were consistent with
      previous extended-release ciprofloxacin studies (e.g., gastrointestinal
      disturbance, fungal superinfections). There were no serious adverse events or
      discontinuations due to adverse events. CONCLUSION: This open-label, non
      comparative trial in adult women demonstrated a rapid improvement in
      uncomplicated UTI symptom severity (6-24 h) and the ability to return to work
      within 24 h following extended-release ciprofloxacin treatment. Clinical cure
      rate and tolerability profile were similar to results of previous extended
      release ciprofloxacin studies.

PMID- 16083535
TI  - Linguistic adaptation and validation into Spanish of the Diagnostic Interview for
      Borderline Personality Disorders-Revised (DIB-R).
AB  - OBJECTIVE: This paper describes the linguistic adaptation and psychometric
      validation into Spanish of the Diagnostic Interview for Borderlines-Revised (DIB
      R) scale for diagnosing borderline personality disorder (BPD). METHODS: A
      conceptual equivalence approach was undertaken, including forward and backward
      translations of the scale and patient debriefing in a pilot phase. BPD and
      control patients were included in the validation study, and all of them were
      administered the scale by well trained interviewers, blinded to the clinical
      diagnosis. Reference diagnosis for BPD was done according to DSM-IV criteria. The
      interview was independently administered in a subset of patients by different
      interviewer to test inter-rater reliability . Reliability and validity of the
      instrument were tested by calculating the Cronbach alpha and Guttman split-half
      coefficients and by receiver operating characteristic (ROC) curve analysis, kappa
      agreement coefficient determination and assessment of sensitivity and specificity
      of the scale. RESULTS: A cohort of 111 subjects, 84 BPD patients (33.6 +/- 9.3
      years) and 27 control subjects (34.9 +/- 9.3 years), were included in the study.
      A cut-off point > or = 7 showed a kappa agreement coefficient of 0.853 (95%
      confidence intervals: 0.739-0.967, p < 0.00001). The figures for sensitivity and
      specificity values were 0.964 (0.899-0.993) and 0.889 (0.708-0.977) respectively.
      Inter-rater reliability showed a kappa coefficient of 0.783 (p < 0.0001).
      CONCLUSION: The Spanish version of the DIB-R showed adequate psychometric
      properties for diagnosing BPD in Spain.

PMID- 16083536
TI  - Tolerability and short-term effectiveness of hylan G-F 20 in 4253 patients with
      osteoarthritis of the knee in clinical practice.
AB  - OBJECTIVE: To determine the tolerability and short-term effectiveness of hylan G
      F 20 (Synvisc) in patients with symptomatic osteoarthritis (OA) of the knee in
      standard clinical practice. RESEARCH DESIGN AND METHODS: Over 800 orthopedic
      surgeons in Germany recorded adverse events (AEs) for approximately five
      consecutive patients each following 3 weekly intra-articular hylan G-F 20
      injections. Patients assessed their pain on a 4-point scale before and 3 weeks
      after the first injection. Potential risk factors for local AEs and possible
      predictors of short-term effectiveness of hylan G-F 20 were explored with
      logistic regression. RESULTS: 4253 patients were treated with 12699 injections by
      840 physicians at 720 sites. Local, treatment related AEs (n = 302) were reported
      in 180 patients (4.2% of patients; 2.4% of injections). The most frequently
      reported AEs were joint effusion (2.4% of patients), joint swelling (1.3%),
      arthralgia (1.2%), joint warmth (0.6%), and injection site erythema (0.3%). Most
      AEs were mild (21.4%) to moderate (40.3%) in nature. One patient experienced a
      serious AE of severe swelling and synovial fluid accumulation judged as possibly
      treatment related. Patients < 70 years old, patients with a longer time since
      diagnosis, and those previously treated with visco-supplementation were more
      likely to experience a local AE. Pain significantly (p < 0.0001) decreased 3
      weeks after the first injection compared with before treatment. Potential
      predictors of hylan G-F 20 short-term effectiveness were being underweight, male
      gender, shorter time since diagnosis, and severe baseline pain. CONCLUSIONS: In
      this population of 4253 patients treated with hylan G-F 20 for OA knee pain, the
      overall incidence of local, treatment-related AEs was low and consistent with
      those reported in the current US product labeling and previously published
      studies. Additionally, short-term effectiveness was confirmed.

PMID- 16083537
TI  - Cost effectiveness of duloxetine compared with venlafaxine-XR in the treatment of
      major depressive disorder.
AB  - PURPOSE: To determine the cost effectiveness of duloxetine, a new serotonin
      norepinephrine reuptake inhibitor, when compared with venlafaxine-XR in treating
      major depressive disorder. METHODS: A cost effectiveness analysis, using a
      decision tree modelled outpatient treatment over 6 months. Analytic perspectives
      were those of society (all direct and indirect costs) and the Ministry of Health
      of Ontario (MoH) as payer for all direct costs. Rates of success and dropouts
      were obtained from a meta-analysis of randomized placebo-controlled trials. Costs
      were taken from standard lists, adjusted to 2005 Canadian dollars; discounting
      was not applied. One-way sensitivity analyses were performed on monthly
      acquisition costs and success rates; Monte-Carlo analysis examined all parameters
      over 10000 iterations. RESULTS: From both perspectives, outcomes all numerically
      favoured venlafaxine-XR (Expected success = 53% and 57%; symptom-free days [SFDs]
      = 52.72 and 57.03 for duloxetine and venlafaxine-XR, respectively). Total
      expected costs/patient treated were, Can dollar 7081 and Can dollar 6551 (MoH),
      Can dollar 20987 and Can dollar 19 997 (societal perspective), for duloxetine and
      venlafaxine-XR, respectively. Expected costs/SFD were Can dollar134 and Can
      dollar 115 (MoH) and Can dollar 398 and Can dollar 351 (societal viewpoint) for
      duloxetine and venlafaxine-XR, respectively. Although results were sensitive to
      changes in success rate within the 95% CI, Monte-Carlo analyses using the ICER
      (incremental cost effectiveness ratio) as outcome found venlafaxine-XR was
      dominant in approximately 78% of scenarios in both perspectives. CONCLUSIONS:
      Differences in pharmacoeconomic outcomes found were modest, but in all cases,
      favoured venlafaxine-XR over duloxetine. Therefore, a possible advantage may
      exist at the population level in the treatment of major depressive disorder in
      Canada. Ultimately, a head to head study of the two drugs would be needed to
      confirm these findings.

PMID- 16083538
TI  - Efficacy and safety of mometasone furoate administered once-daily in the evening
      in patients with persistent asthma dependent on inhaled corticosteroids.
AB  - BACKGROUND: Once-daily dosing with an inhaled corticosteroid (ICS) may simplify
      asthma management and improve patient compliance. Since asthma is frequently
      worse at night, evening dosing appears to be a more obvious choice to accommodate
      the chronobiology of asthma than morning dosing. OBJECTIVE: The primary study
      objective was to compare the efficacy and safety of mometasone furoate (MF) dry
      powder inhaler (MF-DPI) 400 microg qd PM (one 400 microg inhalation) with placebo
      for the treatment of asthma in patients previously dependent on twice a day (bid,
      bis in die) ICS therapy. We also compared different regimens of MF-DPI with each
      other and with placebo. METHODS: This 12-week, multicenter, double-blind, placebo
      controlled study evaluated lung function and asthma symptoms in 400 subjects with
      persistent asthma randomized to MF-DPI 200 microg qd (once a day, quaque die) PM,
      400 microg qd PM as one inhalation from a 400 microg device, 400 microg qd PM as
      two inhalations from a 200 microg device, 200 microg twice daily (bid), or
      placebo. Evening doses were to be taken in the late afternoon or early evening,
      preferably before dinner time. RESULTS: Mean changes from baseline at endpoint in
      FEV1 (forced expiratory volume in 1 s) were similar for MF-DPI 400 microg qd PM
      (one inhalation; 0.41 L), MF-DPI 400 microg qd PM (2 inhalations; 0.49 L), MF-DPI
      200 microg qd PM (0.41 L), and MF-DPI 200 microg bid (0.51 L); and all were
      significantly improved compared with placebo (0.16 L; p < 0.001). Secondary
      efficacy variables, including nocturnal awakenings and use of rescue albuterol,
      were also significantly improved with MF-DPI treatment compared with placebo. All
      treatments were generally safe and well tolerated, with adverse events of mild to
      moderate severity. CONCLUSIONS: Once-daily evening dosing of MF-DPI at doses of
      400 and 200 microg restored lung function and improved nocturnal and daytime
      symptom control in subjects with asthma previously dependent on bid ICS therapy.
      Comparable effectiveness of a total daily dose of 400 microg was demonstrated
      between once daily in the evening and twice-daily administration. The results
      also confirm the effectiveness of MF-DPI 200 microg qd PM, the lowest dose
      studied.

PMID- 16083539
TI  - A clinical comparison of two different prednisolone acetate formulations in
      patients undergoing cataract surgery.
AB  - PURPOSE: This study was conducted to evaluate the efficacy of two topical steroid
      prednisolone preparations (Econopred Plus 1%, prednisolone acetate 1%: EPP; Pred
      Fortedagger 1%, prednisolone acetate 1%: PF) in reducing postoperative
      inflammation in cataract patients. METHODS: This was a 4 week, randomized,
      parallel-group, single-center, active-controlled study. One group of patients
      received postoperative topical EPP while the other group received postoperative
      topical PF. Both medications were dosed 4 times per day for 14 days and then BID
      until the container was empty. Both groups of patients received diclofenac sodium
      QID for 14 days and hydroxypropyl guar (HP-Guar, Systane) QID for 7 days then PRN
      (or as directed). The presence of corneal surface keratitis, anterior chamber
      cells and flare (scales 0-3 for keratitis, 0-5 for cells and 0-4 for flare; 0 =
      none) was evaluated by slit lamp biomicroscopy. RESULTS: EPP produced
      significantly lower (P < 0.05) anterior chamber flare scores 14 days following
      surgery (mean +/- SD: 0.86 +/- 0.53) than PF (1.08 +/- 0.40). Otherwise, there
      were no differences observed between the 2 treatments with respect to keratitis,
      anterior chamber flare or cells at postop days 1, 7, or 28. CONCLUSIONS: This
      comparative trial demonstrated that both formulations of prednisolone acetate 1%
      have similar efficacy in the treatment of postoperative ophthalmologic
      inflammation.

PMID- 16083540
TI  - The impact of migraine on psychological well-being of young women and their
      communication with physicians about migraine: a multinational study.
AB  - OBJECTIVE: To describe the impact of migraine on psychological well-being of
      young women and to evaluate their communication with physicians about migraine.
      RESEARCH DESIGN AND METHODS: This cross-sectional telephone survey was conducted
      in Israel and eight European countries (Finland, Germany, Greece, Italy, Norway,
      Spain, Sweden, and The Netherlands). Random-digit dialing was used to identify
      eligible study participants: women 18-35 years of age with migraine, who used
      medication to treat their migraine, and who were employed or full-time students.
      RESULTS: Of 1810 participants, 42% self-reported having a physician diagnosis of
      migraine. Eighty-six per cent believed that their life would be better if they
      did not suffer from migraines; and 58% of participants felt frustrated, 46% felt
      angry, and 44% felt depressed because of their migraines. Negative feelings
      related to migraine varied substantially from country to country. For example,
      feelings of frustration caused by migraine ranged from 32% in Italy to 84% in
      Finland; feelings of anxiety ranged from 21% in Norway to 57% in Italy; and
      feelings of confusion ranged from 13% in Greece to 61% in Italy. Overall, 81% of
      participants had visited a physician in the past year but only 50% of them had
      discussed their severe headaches or migraines with their physician within the
      year. While 68% of those who had visited a physician stated that they were
      comfortable speaking with their physician about migraine, 71% reported being the
      one who initiated the conversation about severe headaches or migraines. Of all
      participants, 39% did not feel that their physician understood how much severe
      headaches or migraines interfered with their life. CONCLUSIONS: Migraines and
      severe headaches impose a substantial burden on the psychological well-being of
      young women with migraine in Europe and Israel. In general, communication between
      these women and their physicians about migraine is incomplete.

PMID- 16083541
TI  - The DISCOVERY PENTA study: a DIrect Statin COmparison of LDL-C Value--an
      Evaluation of Rosuvastatin therapY compared with atorvastatin.
AB  - BACKGROUND: International guidelines emphasize the need to achieve recommended
      low-density lipoprotein cholesterol (LDL-C) levels in order to reduce morbidity
      and mortality associated with coronary heart disease (CHD). However, many
      patients with hypercholesterolemia fail to achieve LDL-C goals on treatment.
      OBJECTIVE: The primary objective was to compare the efficacy of rosuvastatin and
      atorvastatin for enabling patients to achieve National Cholesterol Education
      Program Adult Treatment Panel III (NCEP ATP III) LDL-C goals. Secondary
      objectives were European LDL-C goal achievement, changes in the lipid profile,
      and safety. RESEARCH DESIGN AND METHODS: This 12-week, multicenter,
      multinational, randomized, open-label trial compared the efficacy and safety of
      rosuvastatin 10 mg with atorvastatin 10 mg in statin-naive and switched patients
      with primary hypercholesterolemia from Brazil, Colombia, Mexico, Portugal, and
      Venezuela. RESULTS: A total of 1124 patients with similar baseline
      characteristics were randomized to the two treatment groups. After 12 weeks of
      treatment, a significantly greater percentage of patients receiving rosuvastatin
      10 mg compared with atorvastatin 10 mg achieved NCEP ATP III LDL-C goals (71.2%
      vs 61.4%, p < 0.001), 1998 European LDL-C goals (73.5% vs 59.2%, p < 0.001) and
      2003 European LDL-C goals (58.9% vs 44.6%, p < 0.001). Rosuvastatin treatment was
      associated with significant reductions in LDL-C and total cholesterol (TC) and,
      in statin-naive patients, a significant increase in high-density lipoprotein
      cholesterol (HDL-C) compared with atorvastatin treatment. Both treatments were
      well tolerated with a similar incidence of adverse events. Clinically significant
      elevations in creatinine, creatine kinase or hepatic transaminases were low and
      similar between treatment groups. CONCLUSIONS: Rosuvastatin 10 mg is
      significantly more effective at achieving NCEP ATP III and European LDL-C goals,
      lowering LDL-C and TC in both naive and switched patients and increasing HDL-C in
      naive patients than atorvastatin 10mg, with a similar safety and tolerability
      profile. This study also provides evidence regarding the comparative effects of
      rosuvastatin versus atorvastatin in Latin American and Portuguese populations.

PMID- 16083542
TI  - Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer's
      disease over a 2-year period.
AB  - OBJECTIVES: Randomised controlled trials that directly compare cholinesterase
      inhibitors for the treatment of Alzheimer's disease have been characterised by
      significant methodological limitations. As a consequence, they have failed to
      establish whether there are differences between agents in this class. To help
      address this question, a double-blind, randomised, controlled, multicentre trial
      was designed to evaluate the efficacy and tolerability of cholinesterase
      inhibitor treatment in patients with moderate to moderately-severe Alzheimer's
      disease over a 2-year period. METHODS: Patients were randomly assigned to
      rivastigmine 3-12 mg/day or donepezil 5-10 mg/day. Efficacy measures comprised
      assessments of cognition, activities of daily living, global functioning and
      behavioural symptoms. Safety and tolerability assessments included adverse events
      and measurement of vital signs. RESULTS: In total, 994 patients received
      cholinesterase inhibitor treatment (rivastigmine, n = 495; donepezil, n = 499),
      and 57.9% of patients completed the study. The most frequent reason for premature
      discontinuation in both treatment groups was adverse events, primarily
      gastrointestinal. Adverse events were more frequent in the rivastigmine group
      during the titration phase, but similar in the maintenance phase. Serious adverse
      events were reported by 31.7% of rivastigmine- and 32.5% of donepezil-treated
      patients, respectively. Rivastigmine and donepezil had similar effects on
      measures of cognition and behaviour, but rivastigmine showed a statistically
      significant advantage on measures of activities of daily living and global
      functioning in the ITT-LOCF population. However, this was not maintained in the
      non-ITT-LOCF populations. In secondary subgroup analyses, AD patients who had
      genotypes that encoded for full expression of the butyrylcholinesterase enzyme
      (BuChE wt/wt; n = 226/340), who were < 75 years of age (n = 362/994) or who had
      symptoms suggestive of concomitant Lewy body disease (n = 49/994) showed
      significantly greater benefits from rivastigmine treatment. CONCLUSIONS:
      Cholinesterase inhibitor treatment may offer continued therapeutic benefit for up
      to 2 years in patients with moderate AD. Although both drugs performed similarly
      on cognition and behaviour, rivastigmine may provide greater benefit in
      activities of daily living and global functioning.

PMID- 16083543
TI  - [The clinical significance of detecting minimal residual disease in acute
      childhood B-cell lymphoblastic leukemia with flow cytometry].
AB  - OBJECTIVE: Flow cytometry may be used to detect minimal residual disease (MRD) in
      acute lymphoblastic leukemia because leukemic cells often display aberrant
      phenotypes when compared to normal cells. The present study was designed to
      establish a flow cytometric method for detecting MRD in children with B-ALL and
      evaluate its clinical prognostic value. The investigators also aimed to study the
      value of the detection of MRD by flow cytometry in childhood B-ALL without
      effective antibody combinations. METHODS: Thirty-six cases of childhood B-ALL
      with effective antibody combinations were performed MRD analysis after induction
      therapy. The authors detected MRD in 6 cases without effective antibody
      combinations by the four-color antibody combinations consisting of
      CD(45)/CD(19)/CD(10)/CD(34) and CD(45)/CD(19)/CD(20)/CD(22) and detected the
      aberrance of the minor subsets of CD(19)(+) cells. RESULTS: (1) Forty-two cases
      of childhood B-ALL were screened for antibody combinations of interest and were
      identified in 86% (36/42) of the cases. The sensitivity of this method was 0.01%.
      (2) Patients with MRD levels > or = 0.01% at 9 and 12 months of therapy had
      significantly low disease-free survival compared with patients with MRD levels <
      0.01%. (3) Six out of seven patients with recurrence in the BM had MRD levels >
      or = 0.1% prior to recurrence. Patients with MRD levels > or = 0.1% during
      chemotherapy had significantly low disease-free survival as compared with
      patients with MRD values < 0.1%. (4) Two out of seven patients with recurrence
      had positive results of the qualitative PCR prior to recurrence. (5) Five
      patients with recurrence had no shift of antigen expression at relapse except
      that a patient missed CD(13). (6) Detectable MRD was not found in six patients
      without effective antibody combinations. CONCLUSION: (1) Flow cytometry is a
      sensitive and specific method for detecting MRD of childhood ALL, and could
      predict the coming relapse. (2) Patients with MRD levels > 10(-3) had poor
      prognosis. (3) The levels of MRD at month 9 and 12 had prognostic value. (4) The
      value of antibody combinations consisting of CD(45)/CD(19)/CD(10)/CD(34) and
      CD(45)/CD(19)/CD(20)/CD(22) should be further investigated in patients without
      effective antibody combinations.

PMID- 16083544
TI  - [Therapeutic effectiveness of CCLG-97 protocol on standard-risk childhood acute
      lymphoblastic leukemia].
AB  - OBJECTIVE: With the improvement of the diagnosis and treatment, the complete
      remission (CR) rate and the survival rate of childhood acute lymphoblastic
      leukemia have been increased in the recent 10 years. The objective of this study
      was to analyze the outcomes of 119 standard-risk childhood acute lymphoblastic
      leukemia (SR-ALL) patients, and explore how to improve the survival rate in ALL.
      METHODS: A total of 119 patients aged 14 months to 15 years were diagnosed as SR
      ALL according to the Suggestion of Diagnosis And Treatment for Childhood Acute
      Leukemia-1993. Among them, seventy-nine were boys and 40 were girls. All of the
      patients were treated with the CCLG-97 protocol and were followed up for a period
      of 20 approximately 78 months. RESULTS: The complete remission rate reached 97.4%
      in four-week induction. Twenty-one patients were out of follow-up, comprising
      63%, 14%, 10%, 8% and 5% of all subjects in 1998, 1999, 2000, 2001 and 2002,
      respectively. The overall survival rates were 93.3%, 90.2%, 88.0%, 85.0%, 85.0%
      and 85.0% in 1 year, 2 years, 3 years, 4 years and 5 years, respectively.
      Relapses occurred in 13 patients (13.8%). Among 9 isolated hematologic relapses,
      5 patients (56%) were given irregular therapy, 2 did not reach CR within 4 weeks
      and relapsed 2 years later, 2 accepted regular therapy, 1 was of hypodiploidy and
      1 T-ALL. Isolated central nervous system (CNS) relapse occurred in 4 patients
      (4.3%). Fifteen patients (12.6%) died, 5 of whom (4.2%) died of complications.
      CONCLUSION: Reinforcing administration and regular therapy are important to
      improve the long-term survival rate in childhood ALL. The clinical classification
      should be adjusted with the improvement of diagnostic methods. CCLG-97 protocol
      decreased the rate of the relapses in SR-ALL and didn't increase the rate of
      therapy-related death. High-dose methotrexate should be used in therapy and its
      dosage, usage and individualized therapeutic regimen should be further studied.

PMID- 16083545
TI  - [Failure of treatment and protocol compliance in patients with acute
      lymphoblastic leukemia].
AB  - OBJECTIVE: To analyze the main reason of failure in treatment and compliance to
      protocol in children with acute lymphoblastic leukemia (ALL) at a single
      institute which is located at the most developed city of China. METHODS: All the
      ALL patients who were diagnosed at the hospital from October 1998 to June 2003
      were analyzed. The data were extracted from the department's tumor registry
      database. Failure in protocol compliance and treatment was analyzed within
      different risk groups, patients' resident area, and time period. The patients who
      had not received any therapy after ALL diagnosis were accounted as early protocol
      compliance failure, those who received therapy for less than 15 days were
      regarded as interim failure in protocol compliance, and those who gave up therapy
      or were lost in follow-up after 15 days with stable disease or complete remission
      (CR) were accounted as late compliance failure. RESULTS: Totally 224 patients
      were diagnosed to have ALL, of them 38 patients went home without receiving any
      therapy, i.e., the rate of early protocol compliance failure was 17.1%. Of the
      remaining 186 patients, 22 (10.5%) belonged to interim protocol compliance
      failure, and 6 cases discontinued the therapy after 15 days treatment, who were
      classified into late compliance failure. Six cases (10.5%) were regarded as
      protocol compliance failure among 57 Shanghainese, and so were 22 cases (17.1%)
      out of 129 non-Shanghainese. There was no significant difference between the two
      groups (chi(2) = 1.332, P > 0.05). Up to a median 40 months follow-up showed that
      in 52 patients (31.7%) the treatment failed, of which 37 cases (22.6%) died of
      incomplete response and relapse, and 15 cases (9.5%) died of therapy
      complication. Among different risk groups, 24 cases (47.1%) came from high risk
      group, 18 (34.0%) from medium risk group, and 5 (9.4%) from low risk group. Very
      significant difference was found among the different risk group (chi(2) = 21.463,
      P < 0.01). Treatment failure was 28.6% (32/112) in non-Shanghainese and 38.5%
      (20/52) in Shanghainese. Total failure in protocol compliance and treatment was
      42.9% (32 + 22/129) in non-Shanghainese and 45.6% (20 + 6/57) in Shanghainese.
      The difference of treatment failure was not significant different between the two
      groups (chi(2) = 1.354, P > 0.05). CONCLUSION: Protocol compliance failure is the
      reason as important as the treatment failure for childhood ALL management
      failure. Either failure should not be neglected. Death from complications was
      relatively high which needs more attention, especially during induction period.
      Unusually high death rate occurred in high and medium risk group patients. The
      grouping criteria may need modification.

PMID- 16083546
TI  - [Effects of human umbilical cord blood mesenchymal stem cells on the expansion of
      CD34+ cells from umbilical cord blood].
AB  - OBJECTIVE: The previous studies indicated that mesenchymal stem cells (MSCs)
      either from umbilical cord blood (UCB) or from bone marrow (BM) had the same
      biological characteristics and the function of secreting hematopoietic growth
      factors (HGFs). The present study aimed to understand the effects of human UCB
      MSCs on the expansion of CD(34)(+) cells from UCB. METHODS: 1. Human UCB
      CD(34)(+) cells were incubated in the system containing UCB MSCs, HGFs and serum
      free medium. 2. The surface markers (CD(34)(+), CD(34)(+)CD(38)(-),
      CD(34)(+)CD(3)(+), CD(34)(+)CD(19)(+), CD(34)(+)CD(33)(+), CD(34)(+)CD(41a)(+))
      on expanded UCB cells were examined by flow cytometry on the 6th and 12th days.
      3. The expanded and unexpanded cells were cultured in semi-solid culturing system
      and checked for colony forming units of granulocyte and macrophage (CFU-GM),
      erythroid burst-forming unit (BFU-E), colony forming units of granulocyte-
      erythrocyte-megakaryocyte-macrophage (CFU-Mix) and colony forming units of high
      proliferative potential (CFU-HPP). RESULTS: 1. The expansion folds of
      CD(34)(+)CD(38)(-) cells from UCB MSCs + HGFs groups on the 6th and 12th days
      were 159.43 and 436.68, respectively. Interestingly, the percentage of
      CD(34)(+)CD(38)(-) cells declined in HGFs group after expanding for 12 days, but
      it rose to 9.98% in the UCB MSCs + HGFs group. 2. Colony forming capacity of
      expanded UCB cells showed that the folds of CFU-Mix and CFU-HPP of UCB MSCs +
      HGFs group increased from day 6 to day 12, but the folds decreased in the HGFs
      group. 3. From day 0 to day 12, CD(34)(+)CD(33)(+) cells and CD(34)(+)CD(41a)(+)
      cells were amplified gradually, but CD(34)(+)CD(19)(+) and CD(34)(+)CD(3)(+)
      cells decreased gradually, and in UCB MSCs + HGFs group this phenomenon was more
      significant than that in HGFs group. CONCLUSION: 1. UCB MSCs containing system
      not only has the ability to expand the primitive HSCs but also has the ability to
      sustain the proliferation of HSCs. 2. UCB MSCs containing system amplified mainly
      myeloid and megakaryocytoid progenitor subsets. These may have clinical
      significance in reducing infection and hemorrhage.

PMID- 16083547
TI  - [A case of congenital leukemia].

PMID- 16083548
TI  - [Biological characteristics and induced differentiation ability of in vitro
      expanded umbilical cord blood mesenchymal stem cells].
AB  - OBJECTIVE: Mesenchymal stem cells (MSCs) from bone marrow are capable of
      differentiating into cells of different tissue lineages such as bone, cartilage,
      and adipose tissue and are the best candidates for tissue engineering. It is well
      accepted that umbilical cord blood (UCB) is a source for hematopoietic stem
      cells. However, controversy exists as to whether UCB contains MSCs and can serve
      as a source of MSCs. Therefore, the aim of this study was to explore the
      biological characteristics and inducing differentiation ability of in vitro
      expanded UCB MSCs. METHODS: UCB was collected on normal full term delivery of
      infants with informed consent (n = 35) obtained from the mothers. Mononuclear
      cells (MNCs) were isolated from UCB by gravity centrifugation and cultured with
      DMEM including 10% fetal bovine serum. The morphology was observed under
      microscope per day. Cytochemical staining was carried out and flow cytometry was
      used to examine the surface antigen phenotype. Fifth passage cells were
      transferred into a different medium and osteogenic differentiation, adipogenic
      differentiation, and neurogenic differentiation were assessed. RESULTS: MSCs
      could be isolated and cultured from MNCs of a few UCB sources. These cells
      displayed fibroblast-like morphology. They withstood over 20 passages without
      significant structural changes. These MSCs were negative for alkaline phosphatase
      (ALP) staining and positive for alpha-naphthol butyric acid esterase (NBE)
      staining. Expression of CD(29), CD(44)and CD(105), especially the human MSCs
      specific markers SH-2 and SH-3 were observed, but CD(3), CD(14), CD(19), CD(34)
      and CD(45) could not be found, indicating that these cells were not of
      hematopoietic origin. Exposure of these MSCs to serum-free osteogenic condition,
      they could differentiate into bone cells and form mineralized matrix as evidenced
      by Alizarin red staining 2 weeks later. When these UCB-derived MSCs were cultured
      in adipogenic medium, morphologic changes in cells as well as the formation of
      neutral lipid vacuoles were noticeable as early as 1 week after induction and
      visualized by staining with oil-red O. Surprisingly, these MSCs were also able to
      differentiate into neuroglial-like cells. Morphology of these induced cells
      resembled that of neurons. Immunocytochemistry showed that they expressed Nestin
      and neuron-specific enolase (NSE), but not glial fibrillary acidic protein
      (GFAP). CONCLUSION: UCB does contain MSCs. These MSCs, which are multipotent,
      could be isolated and cultured from a few UCB sources. UCB might serve as an
      alternative source of MSCs to bone marrow.

PMID- 16083549
TI  - [The cloning of human Smac gene and its pro-apoptotic effect on Burkitt's
      lymphoma cells].
AB  - OBJECTIVE: Second mitochondria-derived activator of caspase (Smac) is a recently
      identified, novel pro-apoptotic molecule, which is released from mitochondria
      into the cytosol during apoptosis. Smac promotes activation of caspases by
      neutralizing members of the inhibitor of apoptosis proteins (IAPs) family, such
      as X-linked inhibitor of apoptosis protein (XIAP). The objective of the study was
      to examine the pro-apoptotic effect of human Smac gene on Burkitt's lymphoma Raji
      cells. METHODS: The full length cDNA of human Smac gene was amplified by reverse
      transcription-PCR from total RNA of HEK-293 cells. The PCR product was ligated
      with linearized vector pGEM-T-easy supplied in the TA cloning kit and sequenced.
      The correct cDNA of full length Smac was subcloned into eukaryocytic expression
      vector pcDNA3.1/myc-his and transfected into human Burkitt's lymphoma cell line
      Raji by lipofectamine-mediated transfection. The expression of full length Smac
      was determined by Western blot. Morphological observation was done with the laser
      scanning confocal microscope by double staining the Raji cells with Hoechest
      33,258 and propidium iodide. Flow cytometry was used to evaluate apoptosis.
      Relative caspase-3 activity was determined by colorimetric assay. RESULTS:
      Recombinant eukaryocytic expression vector pcDNA3.1/Smac, which contained full
      length Smac, was successfully constructed. After pcDNA 3.1/Smac was transfected
      into human Burkitt's lymphoma Raji cell line for 24 hours, Raji cells showed
      apparent apoptosis with a percentage of (43.7 +/- 2.5)%, which was higher than
      that of non-transfected group and free vector-transfected group (P < 0.05).
      Compared with non-transfected group (0.136 +/- 0.036) and free vector-transfected
      group (0.138 +/- 0.026), the relative caspase-3 activity of Raji cells
      transfected by pcDNA3.1/Smac (0.936 +/- 0.041) was significantly enhanced (P <
      0.05). CONCLUSION: Transfection and expression of human Smac gene could
      significantly induce apoptosis of human Burkitt's lymphoma Raji cells. The
      mechanism is associated with the increase of caspase-3 activity.

PMID- 16083550
TI  - [An answer to the question: can promethazine be routinely used in asthmatic
      disease in childhood?].

PMID- 16083551
TI  - [Comparison of the effectiveness of 131-I and antithyroid drugs in the treatment
      of Graves' disease in children].
AB  - OBJECTIVE: To comprehensively evaluate the treatment of Graves' disease in
      children with (131)I and antithyroid drugs (ATD) and to quantitatively assess the
      advantages and disadvantages of them. METHODS: The authors examined the outcome
      of (131)I and ATD treatment in children with Graves' disease at the Hospital of
      Dongshan District in Guangzhou during the period 1997 to 2002. Each of the 2
      groups of patients consisted of 40 patients ranging in age from 8 to 14 years
      (mean 10.7 +/- 2.2). The groups were similar in age, gender, length of disease,
      goiter size, and initial serum thyroid hormone levels. Thyroid status was
      assessed > 2 year after the therapies started. The efficacy of the therapeutic
      methods were scored as follows: the children whose disease was cured were marked
      0, and those who had improvement but were not cured were marked 1, and those who
      remained unchanged were marked 2. After treatment the patients who were
      demonstrated to have ophthalmopathy or more severe ophthalmopathy, hyperthyroid
      heart disease, liver function damage and leukopenia were marked 2 respectively,
      and those who showed temporary hypothyroidism and permanent hypothyroidism were
      marked 1 and 2, respectively. Those who had a relapse of the disease after being
      cured were marked 2. The effects of two groups and total scores were compared.
      RESULTS: The total score of the group treated with (131)I was 34; and the median
      score was 1; the total score of the group treated with ATD was 69, and the median
      score was 1.5; the difference between the two groups was statistically
      significant (P < 0.01). When these two groups were compared, the advantage of
      (131)I in the treatment of this disease was clear. The incidences of
      ophthalmopathy and improvement of ophthalmopathy of the two groups were not
      significantly different (P > 0.05). No significant difference was found in
      incidence of hypothyroidism between the two groups (P > 0.05). There was no
      significant worsening or new development of ophthalmopathy or hypothyroidism
      after (131)I and ATD treatment. The rate of relapse of hyperthyroidism among
      patients cured with (131)I was significantly lower than that among patients cured
      with ATD (P < 0.05). In the patients treated with (131)I the incidences of
      hyperthyroid heart disease, liver function damage, leukopenia and so on were
      significantly lower than those of patients treated with ATD (P < 0.05).
      CONCLUSIONS: (131)I therapy was superior to the ATD in treatment of the children
      with Graves' disease. Observations for more than 2 years after treatment with
      (131)I showed that there were no harmful side effects or complications. (131)I
      can be recognized as the safer, more convenient and effective treatment than ATD
      for Graves' disease in children.

PMID- 16083552
TI  - [Expression of peripheral blood neutrophil CD64 in neonatal septicemia].
AB  - OBJECTIVE: Neonatal septicemia is a common and severe infection, which often
      results in death. Early diagnosis and treatment of neonatal septicemia may help
      decrease neonatal mortality. Recently, many studies sought to explore the
      possibility of early diagnosis of this disease. The high affinity Fcgamma
      receptor I (CD(64)) was purposefully chosen as a potential marker for identifying
      neonatal septicemia. The present study was designed to evaluate neutrophil CD(64)
      level for early diagnosis of neonatal septicemia. METHODS: Eighty-nine suspected
      neonatal septicemia cases were recruited into the study. Five non-specific
      indices, i.e., C-reactive protein (CRP), micro-erythrocyte sedimentation rate
      (mESR), white blood cell count, platelet count and the ratio of immature
      neutrophil count to total neutrophil count were measured for each patient. The
      patients were divided into septicemia group (n = 39) and non-septisemic infection
      group (n = 50) according to the diagnostic criteria for neonatal septicemia.
      Nineteen hospitalized neonates with non-infectious diseases were enrolled as
      controls (n = 19). The levels of peripheral blood neutrophil CD(64) were measured
      by using flow cytometry. The positive rate, sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of CD(64) were
      calculated. RESULTS: The levels of peripheral blood neutrophil CD(64) in
      septicemia patients were (75.6 +/- 8.9)%, which were significantly higher than
      those of non-septisemic infection group (29.1 +/- 6.2)% and control group (5.1 +/
      1.1)% (P < 0.05), respectively. There were no significant differences in the
      levels of CD(64) expression between the patients with Gram-negative (79.5 +/-
      3.5)% and Gram- positive (76.4 +/- 5.0)% (P > 0.05) bacterial infection. The
      levels of CD(64) of the cases with septicemia significantly decreased at day 10
      of treatment with antibiotics. The detection of CD(64) (cutoff value > 30%) for
      suspected septicemia showed high sensitivity (97.4%), specificity (84.0%), PPV
      (82.6%), and NPV (97.6%). The positive rate of CD(64) detection (62.9%) was much
      higher than that of the blood culture test (19.1%) and that of the five
      nonspecific indices (29.2%, P < 0.05, respectively). CONCLUSION: The expression
      of CD(64) increased in neonatal septicemia cases. The measurement of cell surface
      expression of CD(64) on neutrophils may be helpful to early diagnosis, evaluation
      of severity of infection and observation of therapeutic effects for neonatal
      septicemia.

PMID- 16083553
TI  - [Association of vitamin D receptor gene Apa I polymorphism with vitamin D
      deficiency rickets].
AB  - OBJECTIVE: To study the association between vitamin D receptor (VDR) gene Apa I
      polymorphism and vitamin D deficiency rickets in children of Shanxi Han ethnic
      group, and to explore the significance of individual hereditary factors in the
      development of rickets. METHODS: This was a case control study. The grouping
      criteria were serum 25(OH)D(3) level, blood bone alkaline phosphatase and
      clinical symptom, respectively. The laboratory test methods were enzyme linked
      immunoassay and radioimmunoassay. PCR-RFLP technology was applied to examine VDR
      gene Apa I site polymorphism and Hardy-Weinberg hereditary balance test was used
      to examine the coincidence of gene distribution. RESULTS: Frequencies of AA, Aa
      and aa genotypes were 5.0%, 52.5% and 42.5% in the rickets group and 4.4%, 55.9%
      and 39.7% in the control group, respectively. Frequencies of A and a genotypes
      were 31.3% and 68.7% in the rickets group and 32.3% and 67.7% in the control
      group, respectively. There was not significant difference in the frequency
      distribution of VDR genotype and allelic genes between two groups (chi(2) =
      0.089, P > 0.05; chi(2) = 0.028, P > 0.05). There was significant difference in
      the serum 25(OH)D(3) between two groups (t = -8.919, P < 0.01). CONCLUSION: The
      distribution of VDR gene Apa I polymorphism in children of Han ethnic group is
      balanced relatively. The Frequency of a allelic genes is 67.7% which is therefore
      the superior gene. VDR gene polymorphism might not be important in an
      individual's susceptibility to development of vitamin D deficiency.

PMID- 16083554
TI  - [Apoptosis and expressions of PDCD5 and Caspase-3 in renal tissues of children
      with lupus nephritis].
AB  - OBJECTIVE: To improve the understanding of the pathogenesis of lupus nephritis
      (LN) by studying the relationship between apoptosis and proliferation in children
      with LN. METHODS: Thirty-one children (23 girls, 8 boys, aged 6-16 years) with
      biopsy-proven LN (21 type IV, 6 type V, 2 type II and 2 type III) and nine
      controls were included in the study. Apoptosis was detected by in situ nick-end
      labeling techniques (TUNEL) in renal biopsy samples. Proliferation was shown by
      PCNA detection. Immunohistochemistry was employed to detect the expressions of
      PCNA, PDCD5 and Caspase-3. The images of glomeruli (G) and renal tubuli (T) were
      selected randomly on each biopsy sample, respectively, and transferred into
      computer by SECOM video camera. The quantity of PDCD5 and Caspase-3 expressions
      were evaluated according to the average intensity of PDCD5 and Caspase-3.
      RESULTS: 1. Compared to control group, the patients with LN had increased
      apoptotic cells (G: 0.14 +/- 0.09 vs. 0.86 +/- 0.26; T: 0.16 +/- 0.07 vs. 1.16 +/
      0.42; P < 0.01) and increased PCNA positive cells (G: 0.47 +/- 0.25 vs. 8.45 +/-
      2.83; T: 1.32 +/- 0.15 vs. 13.73 +/- 3.54; P < 0.01) in glomeruli and renal
      tubuli. The high ratios of PCNA/apoptosis (P/A) were observed in glomeruli (3.37
      +/- 1.93 vs. 10.01 +/- 2.96, P < 0.01) and tubuli (8.94 +/- 1.79 vs. 12.81 +/-
      3.91, P < 0.05) in LN group. 2. There was no difference in expression of PDCD5 in
      glomeruli between LN children and controls (0.09 +/- 0.05 vs. 0.08 +/- 0.02, P >
      0.05). The expression of PDCD5 in renal tubuli decreased significantly in LN
      children compared with controls (0.13 +/- 0.05 vs. 0.21 +/- 0.07, P < 0.01). 3.
      The expression of Caspase-3 in children with LN increased significantly in
      glomeruli and tubuli compared with that in controls (0.22 +/- 0.07 vs. 0.05 +/-
      0.02; 0.08 +/- 0.03 vs. 0.05 +/- 0.01; P < 0.01). 4. The number of glomerular
      apoptotic cells showed a positive correlation with the expression of Caspase-3 (r
      = 0.718, P < 0.01), but no correlation with the expression of PDCD5 in all cases
      (r = 0.054, P > 0.05). The intensity of PDCD5 expression in glomeruli and renal
      tubuli showed no correlation with that of Caspase-3 expression in all cases (r =
      0.061, P > 0.05, r = 0.049, P > 0.05). Stepwise multiple regression revealed that
      the number of apoptotic cells in renal tubuli correlated negatively with the
      intensity of PDCD5 expression, whereas correlated positively with intensity of
      Caspase-3 expression in all cases. CONCLUSIONS: 1. Although the number of
      apoptotic cells in the kidney of LN was more than that in the kidney of control
      group, the apoptosis in the kidney of LN was relative insufficient compared with
      the proliferation. 2. Caspase-3 was involved in the apoptosis of glomeruli and
      renal tubuli of LN. 3. It was unclear if PDCD5 participated in the apoptosis of
      glomeruli of LN. While PDCD5 might participate the apoptosis of renal tubuli in
      LN.

PMID- 16083556
TI  - [Acute renal failure induced by primary hyperuricemia in children: a case
      report].

PMID- 16083555
TI  - [Expression of signal transducer and activator of transcription 6 in rat asthma
      model and the modulatory effect of dexamethasone].
AB  - OBJECTIVE: To study the expression of signal transducer and activator of
      transcription 6 and its mRNA in rat asthma model and the modulatory effect of
      dexamethasone (DXM). METHODS: Thirty male SD rats were randomly divided into
      three groups: the control group, asthma group and DXM group. The rats in each
      group were sacrificed 24 h after the last challenge. In the experiment, the rat
      model of asthma was established by ovalbumin (OVA) challenge method. The lung
      tissue was taken from the left lung, and bronchoalveolar lavage fluid (BALF) was
      collected from the right lung. The total cell numbers, eosinophils (EOS) count
      and differentiated cell counts in BALF were performed on different count fluids.
      The concentrations of IL-4 in serum and BALF were measured by using sandwich
      ELISA. The protein expressions of STAT6 were detected with immunohistochemical
      techniques. The mRNA expressions of STAT6 were detected with in situ
      hybridization. RESULTS: (1) The total cell counts in BALF, the absolute counts of
      EOS, and the ratios of eosinophils to the total cell numbers (EOS%) of asthma
      group were all significantly higher than those of the control group (P < 0.01).
      The total cell counts in BALF, the absolute counts of EOS, and EOS% of DXM group
      were all significantly lower than those of asthma group (P < 0.01). (2) The
      concentrations of IL-4 in BALF and serum of asthma group [(25.7 +/- 7.4) ng/L,
      (34.2 +/- 10.5) ng/L] were significantly higher than those of control group [(8.6
      +/- 3.0) ng/L, (12.1 +/- 2.9) ng/L] (P < 0.01). The concentrations of IL-4 in
      BALF and serum of DXM group were significantly lower than those of asthma group.
      (3) Immunohistochemistry showed that the protein content of STAT6 around the
      bronchus of asthma group (0.171 +/- 0.025) was significantly higher than that of
      the control group (0.082 +/- 0.022) (P < 0.01), while that of DXM group (0.114 +/
      0.013) was significantly lower than that of asthma group. The epithelial cells
      were the cells. In situ hybridization showed that the mRNA expression of STAT6
      around the bronchus of asthma group (0.180 +/- 0.013) was significantly higher
      than that of the control group (0.091 +/- 0.012) (P < 0.01), while that of DXM
      group (0.114 +/- 0.010) was significantly lower than that of asthma group. (4)
      There was a significant correlation between the concentration of IL-4 in BALF,
      the content of STAT6 and STAT6 mRNA, respectively, in the epithelial cells of
      bronchus. There was a significant correlation between the absolute numbers of EOS
      and EOS% in BALF, the content of STAT6 and STAT6 mRNA, respectively, in the
      epithelial cells of bronchus. CONCLUSIONS: STAT6 protein and STAT6 mRNA were
      found strongly expressed in rat asthma model and the epithelial cells were the
      chief expressing cells. Dexamethasone had an inhibitory effect on airway
      inflammatory cells infiltration. It significantly depressed STAT6 and mRNA
      expression. Which may be a key process in modulatory mechanism of asthma.

PMID- 16083557
TI  - [Effects of marginal vitamin A deficiency and intervention on learning and memory
      in young rats].
AB  - OBJECTIVE: Previous studies have demonstrated that vitamin A and its active
      derivatives function as essential competence factors for long-term synaptic
      plasticity within the adult brain. But little is known if marginal vitamin A
      deficiency (MVAD) beginning from embryonic period affects the brain development
      and the ability of learning and memory in young rats. The aim of this study was
      to identify the effects of MVAD and vitamin A intervention (VAI) on learning,
      memory and the hippocampal CA1 long-term potentiation (LTP) in young rats.
      METHODS: Rats were divided into control, MVAD and VAI groups in this study. In
      control group (10 young rats) the dams and pups were fed with normal diet (VA
      6500 IU/kg). In MVAD group (19 young rats) the dams and pups were fed with MVAD
      diet (VA 400 IU/kg). In VAI group (9 young rats) the dams were fed with MVAD diet
      and the pups were fed with normal diet from postnatal week 4. All the young rats
      were killed at the age of 7 weeks. During the last week of the experiment, the
      shuttle box active avoidance reaction tests were carried out. At week 7, the
      hippocampal CA1 LTP was detected by electrophysiological technique and relative
      intensity of fluorescence in cells in hippocampal slices was measured by confocal
      laser scanning microscopy labeled by fluo-3. RESULTS: (1) The times to reach the
      learning standard in both VAI group (28.8 +/- 4.1) and MVAD group (45.6 +/- 12.1)
      were more than control group (17.1 +/- 4.4) (P < 0.01), and that of MVAD group
      was more than VAI group (P < 0.05) in active avoidance reaction tests. (2) The
      changes of field excitatory postsynaptic potentials (fEPSP) slope for MVAD group
      (22.9% +/- 9.4%) and VAI group (29.5% +/- 13.7%) were less than that of control
      group (57.5% +/- 27.3%), respectively (P < 0.01). No significant difference was
      found between VAI and MVAD groups (P > 0.05). (3) No significant differences of
      relative intensity of fluorescence in cells were found among the three groups
      before the tetanus stimulation. However, the significantly low relative intensity
      of fluorescence in cells was seen in MVAD (65.1 +/- 17.0) and VAI (85.8 +/- 17.1)
      groups compared with control group (113.6 +/- 20.5) after the tetanus stimulation
      (P < 0.01), and that of VAI group was higher than that of MVAD group (P < 0.05).
      CONCLUSION: MVAD beginning from embryonic period impairs learning, memory and LTP
      in young rats. But the losses might not be reversible if the vitamin A
      supplementation is late especially missing the critical period of hippocampus
      development. According to the experimental data, it is speculated that vitamin A
      may modulate the influx of calcium ion to influence the LTP and lead to the
      change of learning and memory.

PMID- 16083558
TI  - [Value of 8-iso-prostaglandin F2a determination in assessment of neonatal hypoxic
      ischemic encephalopathy].

PMID- 16083559
TI  - [The adverse reaction of L-asparaginase and its prevention].

PMID- 16083560
TI  - [Clinical observation and follow-up study on acute promyelocytic leukemia in
      childhood treated mainly with arsenic trioxide].

PMID- 16083561
TI  - [Congenital complex tracheobronchial abnormality].

PMID- 16083562
TI  - [An infant with positive anticardiolipitin antibody and prolonged activated
      partial thromboplastin time].

PMID- 16083563
TI  - [Pauci-immune necrotizing lupus nephritis: report of one case].

PMID- 16083564
TI  - [Congenital aortic arch twist abnormality with thoracic aorta aneurysm: a case
      report].

PMID- 16083565
TI  - [Obstruction of superior vena cava resulting from left coronary artery-superior
      vena cava fistula: a case report].

PMID- 16083566
TI  - [Intracranial hemorrhage in children in the acute stage of Kawasaki disease].

PMID- 16083567
TI  - [Neonatal Mobius syndrome].

PMID- 16083568
TI  - [The state of classification for pediatric myelodysplastic syndromes].

PMID- 16083569
TI  - [Prevention and therapy of atherosclerosis in childhood].

PMID- 16083570
TI  - [A brief description of the 15th International Conference on Prevention of Child
      Abuse and Neglect].

PMID- 16083571
TI  - [A summary of National Conference of Pediatric Cardiovascular Diseases in 2004].

PMID- 16083572
TI  - [Mesenchymal chondrosarcoma in the pelvic cavity: a case report].

PMID- 16083574
TI  - [Cervical posterior laminoplasty operation using coralline hydroxyapatite].
AB  - OBJECTIVE: To study the results of using coralline hydroxyapatite (CHA) in
      cervical posterior laminoplasty operation. METHODS: Two hundred and fifty-six
      patients underwent cervical spinous process-splitting laminoplasty using CHA. All
      patients had been followed up over 3 months. One hundred and forty-two patients
      were followed up at least 2 years. All patients had spinal stenosis at least at 3
      levels or OPLL. The average follow up time was 34.6 months. RESULTS: The CHA
      grafts were stable between the split spinous processes. The union rate of CHA was
      83.5%. After operation, the spinal cord moved dorsally, and the anteroposterior
      compression ratio had been improved from 0.19 to 0.42. No apparent kyphosis
      occurred. The JOA score improvement rate was 58.3%. There were 24 patients (17%)
      with axial symptom. CONCLUSION: Cervical posterior laminoplasty operation using
      coralline hydroxyapatite may achieve good results.

PMID- 16083576
TI  - [Evaluation and treatment of congenital scoliosis with split cord malformation].
AB  - OBJECTIVE: To discuss the diagnosis and surgical treatment of congenital
      scoliosis (CS) with split cord malformation (SCM). METHODS: From May 1999 to June
      2004, 353 cases of CS were admitted, and 58 cases were diagnosed CS combined with
      SCM via myelography and (or) CTM. According to Pang's classification for SCM,
      patients were divided into type I SCM and type II SCM. Two cases gave up
      operation, and surgeries were performed in 56 patients. Except that one case with
      arachnoid cyst underwent intraspinal exploration, all other 55 cases underwent
      spinal correction without dealing with the intraspinal abnormalities. Clinical
      manifestation, radiological findings, operative methods and results were
      retrospectively analyzed in this paper. RESULTS: There were 11 patients (19%)
      with type I SCM and 47 patients (81%) with type II SCM. In the 56 cases who had
      surgical treatment, the Cobb angle in the patients with type I SCM (11 cases) was
      (60 +/- 25) degrees, and in type II SCM (45 cases) was (67 +/- 21) degrees pre
      operation. The Cobb angle in type I SCM was (29 +/- 13) degrees and in type II
      SCM was (39 +/- 19) degrees post-operation, with the correction rate (51 +/- 17)%
      and (41 +/- 24)% respectively. No statistic differences were found between both
      types. And there were no new neurological deficits in both groups after the
      spinal correction operation. After average 17.3 months (4-59 months) follow-up,
      the correction loss was (6 +/- 10) degrees, (5 +/- 8) degrees in 7 patients with
      type I SCM and (6 +/- 10) degrees in 19 patients with type II SCM. There was no
      statistic difference in correction loss between both types. In the follow-up, the
      neurological symptoms and signs of the patients were stable. CONCLUSION:
      Considering the incidence of intraspinal anomalies in patients with congenital
      scoliosis, intraspinal examination via myelography, CTM or MRI should be
      performed prior to spinal correction surgery. For congenital scoliosis with type
      I SCM, the bone spur need not be excised before spinal correction if there is no
      signs of spinal cord tethered and the bone spur locate in the middle of the split
      cord where there are much space to accommodate it. For congenital scoliosis with
      type II SCM, if there are no progressive neurological manifestations, the split
      cord in the single tubular can tolerate the manipulation of spinal correction as
      the normal spinal cord.

PMID- 16083577
TI  - [Anatomic identification of the location of the pedicle of atlas with the lateral
      mass of C2 to C4 as the landmark].
AB  - OBJECTIVE: To study the relevant position of the pedicle of C1 to the lateral
      mass of C(2-4), set up an identification technique for the entry point decision
      of C1 pedicle screw by using the lateral mass of C(2-4) as anatomic landmarks.
      METHODS: Twenty cadaver specimens were used to measure the distance from the
      sagittal midline of spine to the medial border, the midpoint and the lateral
      border of C1 pedicle or the lateral mass of C2, C3 or C4. The anatomic relation
      between the measurements data of C1 pedicle and that of the lateral masses of the
      cervical vertebrae were analyzed, and the technique of C1 pedicle screw fixation
      was established. RESULTS: The average medial border of the lateral mass of C2, C3
      and C4 was 0.37 mm, 0.27 mm and 0.24 mm lateral to that of C1 pedicle, the
      average midpoint of the lateral mass of C2, C3 and C4 was 1.18 mm, 1.41 mm and
      1.74 mm lateral to that of C1 pedicle, and the average lateral border of the
      lateral mass of C2, C3 and C4 was 1.96 mm, 2.54 mm and 3.24 mm lateral to that of
      C1 pedicle, respectively. CONCLUSION: There is a steady anatomic location
      relation between C1 pedicle and the lateral mass of C2, C3 or C4. As well as the
      lateral mass of C2, the lateral mass of C3 or that of C4 could be convenient
      anatomic landmarks to determine the location of C1 pedicle and the position of C1
      pedicle screw entry point.

PMID- 16083578
TI  - [Trabecular bone micro-architecture in adolescent idiopathic scoliosis compared
      between concave and convex site of the facet joints].
AB  - OBJECTIVE: To evaluate the trabecular bone micro-structure from different sites
      of spine in adolescent idiopathic scoliosis patients. The target site consisted
      of the bilateral facet joints from apical vertebrae and from end vertebrae.
      METHODS: Nine AIS patients with mean age 14.9 years (range 12-17 years) and mean
      Cobb angle 56 degrees (ranged 48 degrees-84 degrees) were recruited into this
      study. Corrective surgery was indicated to these patients, and facet joint
      biopsies were collected during decortications for spinal fusion. Biopsy consents
      were obtained from patients. Bone specimens were fixed with routine histology
      procedures and scanned by micro computer tomography (muCT40, Scanco Medical,
      Switzerland). Ten pairs of facet joint were harvested from apical vertebrae and
      12 pairs from end vertebrae. Three-dimensional reconstructed images with the
      resolution of 20 microm were achieved for histomorphometric analysis. RESULTS:
      The values of BV/TV (0.268 vs. 0.354, P < 0.05), TbTh (0.20 vs. 0.24, P < 0.05),
      TbSP (0.66 vs. 0.56, P < 0.05) and BS/BV (12.7 vs. 10.4, P < 0.05) between convex
      and concave side at the apex area were significantly different. No difference was
      found in any structural parameters between left and right side at end area, and
      upper thoracic (T5, 6) and thoracolumbar (T12, L1). CONCLUSION: Due to asymmetric
      compression and tension shared between convex and concave side, more bone and
      thicker and more profound trabecular bones are observed in the concave side than
      in the convex side, which seems to resist the progression of spinal curvature.
      This finding suggests that the provocative factors which cause the progression of
      the curve in certain patients may not lie in the bone component of spine.

PMID- 16083579
TI  - [The study of the C5 nerve root palsy after surgery of cervical spondylosis].
AB  - OBJECTIVE: To explore the clinical features, treatment and prognosis of the C5
      palsy after surgery of cervical spondylosis. METHODS: Two hundred and twenty
      three cases treated from March 1994 to October 2003 were retrospectively
      reviewed. RESULTS: Seven of the 223 cases developed the complication of C5 palsy,
      manifesting the paresis of the deltoid muscle as well as the sensory deficits and
      (or) intractable pain in shoulder. The incidence was 3.1%. In this study, 2 cases
      occurred in the anterior subcorpectomy, 5 cases developed in the laminoplasty
      with 1 case on the opened side, 3 cases on the hinged side and 1 case on both
      sides. All the 7 cases with the C5 palsy recovered within 2 weeks to 6 months.
      CONCLUSION: The C5 palsy can develop either anterior decompression or posterior
      open-door laminoplasty of cervical spondylosis. Generally speaking, patients with
      postoperative C5 palsy can be cured by conservative measures. And prognosis is
      good.

PMID- 16083580
TI  - [Vascularized pedicle iliac crest for the repair of bone and soft tissue defect
      of lower extremity].
AB  - OBJECTIVE: To study the role of transplantation of the vascularized pedicle iliac
      crest for the repair of bone and soft tissue defect of lower extremity. METHODS:
      The vascularized pedicle iliac crest was designed for the repair of bone and soft
      tissue defect of lower extremity according to anatomic feature of leg and foot.
      Skin graft was used for coverage of the iliac flap. RESULTS: Skin survival could
      demonstrate the survival of the vascularized pedicle iliac crest indirectly one
      week postoperatively. Skin survived completely in 4 cases and partly in 3 cases.
      Callus was seen at the transplantation site one month postoperatively, and K
      wires were removed 4 months later in the cases of metatarsal defect. The external
      fixators were removed in the cases of tibia defect 6 to 8 months postoperatively.
      The functions of lower extremities were restored in 2 to 4 months. The bone and
      soft tissue defects were repaired, and ultimate function and cosmetic effects
      were satisfied after the mean follow up of 10 months (ranged from 6 to 15
      months). CONCLUSION: Transplantation of the vascularized pedicle iliac crest is
      an ideal method for the repair of bone and soft tissue defect of lower extremity.
      The operation can be performed in one stage. The functions and cosmetic effects
      are better than the traditional methods.

PMID- 16083581
TI  - [Open reduction and internal fixation of displaced intra-articular fractures of
      the calcaneus].
AB  - OBJECTIVE: To evaluate the results of intra-articular calcaneal fractures treated
      with open reduction and internal fixation. METHODS: Thirty-five displaced intra
      articular calcaneal fractures in 34 patients were treated with open reduction and
      internal fixation from August 2001 to April 2003. Fracture classification was
      based on Sanders classification. Extended lateral approach, and fixed the
      fractures with AO titanium plate for calcaneus were performed. Bone graft was
      used in selected patients. Thirty-five fractures in thirty-four patients were
      evaluated using radiographic examinations and ankle hindfoot clinical rating
      system of the American Orthopaedic Foot and Ankle Society (AOFAS). Average follow
      up was 18.3 months (range from 12 to 32 months). RESULTS: There were 30 type II
      fractures and 5 type III fractures. Average Bohler's angle was 5.6 degrees
      preoperatively and 28.2 degrees finally. Roentgenographic evaluation of calcaneal
      body dimensions showed restoration of heel height (97.7%) to virtually normal.
      Anatomic or near anatomic reductions were obtained in 80% of the cases. The
      average score was 88.1 for type II fractures, and 78.8 for type III fractures.
      Excellent or good clinical results occurred in 82.8% type II fractures, and 60.0%
      type III fractures. The overall excellent or good rate was 79.4%. CONCLUSION:
      From the results, open reduction and internal fixation for Sanders type II and
      type III fractures are recommended.

PMID- 16083582
TI  - [Dynamic observation of the biomechanic properties of sciatic nerve at the suture
      site in rats following repairing].
AB  - OBJECTIVE: To observe the biomechanic properties of sciatic nerve at the suture
      site in rats following repairing. METHODS: The right sciatic nerves of 40 white
      Sprague-Dawley 300-350 gm rats were exposed, cut and then repaired with 10-0
      nylon sutures, laced in the epineurium. 0, 1, 3, 6 weeks after operation, the
      tensile strength of the sciatic nerves were measured, the data analyzed
      statistically. RESULTS: The load-elongation curves for both the normal unoperated
      and operated nerves had the similar shape. The tensile strength of the 0 week was
      significant difference to 1, 3 and 6 weeks (P < 0.01). No significant difference
      was found among 1, 3 and 6 weeks. CONCLUSION: The tensile strength of the injured
      nerves are recovered in the first week and resistant in 6 weeks after repairing.

PMID- 16083583
TI  - [The study of total spondylectomy in the treatment of cervical spinal tumors].
AB  - OBJECTIVE: To study the surgical indications, approaches and the clinical results
      of the total spondylectomy and instrumentation reconstruction in the treatment of
      cervical spinal tumor. METHODS: From October 1998 to October 2003, 39 patients
      with lower cervical bone tumors, including 34 cases with primary tumor and 5
      cases with metastatic tumor, were admitted and operated on with total
      spondylectomy. The patients underwent anteroposterior total spondylectomy
      including anterior cervical plating, titanium mesh reconstruction and posterior
      instrumentation based on the location of tumor lesions in the lower cervical
      spine. One vertebral level total spondylectomy was performed in 29 cases, two
      level in 7 cases and three level in 3 cases. RESULTS: The postoperative follow-up
      ranged from 6 months to 4 years. A majority of patients achieved good results
      postoperatively. Nineteen cases had complete relief of neurological status. One
      patient died of multiple metastases and systemic failure 24 months later. One
      case with malignant neurilemmoma developed local recurrence one year
      postoperatively. CONCLUSION: Anteroposterior total spondylectomy and
      reconstruction can reduce local recurrence, improve neurological function and
      increase operation therapeutic effect. Meanwhile, the technique of cervical total
      spondylectomy carries relatively greater risks and should be more attention to
      the operation indication.

PMID- 16083584
TI  - [Adenovirus mediated antisense c-myc gene on the chemotherapy sensitivity of
      osteosarcoma cells to cisplatin].
AB  - OBJECTIVE: To construct the recombinant adenovirus encoding antisense c-myc
      fragment and to investigate its effect on the chemotherapy sensitivity of
      osteosarcoma MG-63 cells to cisplatin. METHODS: The recombinant adenovirus (Ad
      Asc-myc) encoding antisense c-myc fragment was constructed by cloning c-myc cDNA
      of about 720 base pairs in a reverse direction into adenovirus vector, then
      undergoing recombination, amplifying and being complemented in vivo. The
      osteosarcoma MG-63 cells were transfected by the Ad-Asc-myc in vitro, and Wright
      staining, Acridine Orange staining, Western Blot, MTT, Flow Cytometry (FCM) were
      used to study cell morphology, expression of c-myc protein, tumor cell
      proliferation in vitro, apoptosis and cell cycle change. RESULTS: Ad-Asc-myc
      encoding antisense c-myc fragment was obtained with the titer of 2 x 10(9)
      pfu/ml. Ad-Asc-myc down-regulated the expression of c-myc protein after
      transfected MG-63 cells for 48 h, combined with the treatment of 2.0, 5.0
      microg/ml cisplatin for 2 h could inhibit tumor cells proliferation in vitro by
      33.4% and 54.2% respectively, which were significantly difference compared with
      control recombinant adenovirus (Ad-LacZ) groups (P < 0.05). Acridine Orange
      staining and FCM analysis showed that Ad-Asc-myc could induce apoptosis of
      transfected cells, which was enhanced by the treatment of cisplatin cell. Cycle
      analysis showed that obvious G2/M phase arrested in transfected cells.
      CONCLUSION: Ad-Asc-myc increases the chemotherapy sensitivity of osteosarcoma MG
      63 cells to cisplatin as well as induced apoptosis.

PMID- 16083585
TI  - [In vitro antitumor immune response induced by fusion of dendritic cells and
      Ewing's sarcoma cells].
AB  - OBJECTIVE: Human Ewing sarcoma A673 cells and human peripheral blood-derived DCs
      were fused to induce an antitumor activity against human EW. METHODS: EW A673
      cells and human peripheral blood-derived DCs were fused with polyethylene glycol
      (PEG). RESULTS: Mature DCs with highly expressed surface markers (CD80, CD86,
      CD83 and HLA-DR) were generated in vitro and flow cytometry. It showed that the
      highest fusion efficiency was 23.01%. T cell proliferation assay indicated that
      the novel dendritomas in fused DCs/A673 cells were the most potent in activation
      of autologous T cell proliferation. The IFN-gamma assay showed that The IFN-gamma
      secretion by CTLs activated by the novel dendritomas increased more than by other
      stimulators. CTL assay demonstrated that the novel dendritomas induced A673 cell
      specific cytotoxic responses to lyse the A673 cells in the context of MHC class
      I. CONCLUSION: The data indicates that fusion of tumor cells with DCs is an
      attractive strategy to induce tumor rejection.

PMID- 16083586
TI  - [The preparation, structure evaluation and preliminary application of biomimetic
      biphasic calcium phosphate scaffold].
AB  - OBJECTIVE: To fabricate biomimetic biphasic calcium phosphate BCP ceramic
      scaffolds using three-dimensional (3D) gel-lamination technology and evaluated
      their structure with 3D parameters and related method. METHODS: Series two
      dimensional images of femoral head's specimen of dogs were obtained by micro
      computed tomography (Micro-CT). According to these images, porous biomimetic
      biphasic calcium phosphate (BCP) ceramic scaffolds with oriented trabecular
      structure were fabricated by three-dimensional (3D) gel-lamination technology.
      And then, the three-dimensional structure of the scaffolds were reconstructed by
      computer according to Micro-CT images of these scaffolds and evaluated by three
      dimensional parameters. These parameters included bone volume fraction (BVF,
      BV/TV), bone surface/bone volume (BS/BV) ratio, trabecular thickness (Tb.Th),
      trabecular number (Tb.N), trabecular spacing (Tb.Sp) and structure model index
      (SMI). The biomechanical properties and biocompatibility of these scaffolds were
      also evaluated in the study. Six scaffolds, which were combined with BMCs (bone
      mesenchymal cells, BMCs), were planted into the bone defect of six dogs' femoral
      head respectively. RESULTS: There was no significant difference between
      trabecular samples and BCP scaffolds in BV/TV, Tb.Th, Tb.N, and Tb.Pf (P > 0.05).
      The trabecular system of the scaffold, which had some orientation, represented
      plate-like model. With a micro-porous porosity of 62%, the average compressive
      modulus and ultimate strength along the axis of the scaffolds reached (464.0 +/-
      36.0) MPa and (5.6 +/- 0.8) MPa respectively. The results of animal test
      indicated that the trabeculae of these scaffolds were covered by a layer of new
      bone after 10 weeks of operation. CONCLUSION: Porous BCP scaffolds have been
      produced with oriented microarchitectural features designed to facilitate
      vascular invasion and cellular attachment and with initial mechanical properties
      comparable to those of trabecular bone.

PMID- 16083587
TI  - [In vitro study of combination rhOPG-Fc and alendronate on inhibition
      osteoclast].
AB  - OBJECTIVE: To study the effect of combination rhOPG-Fc and alendronate on mature
      osteoclasts. METHODS: Recombinant human osteoprotegerin secretory expression in
      P. pastoris was performed. Osteoblasts were got from new born mouse skeletal bone
      and proved by ALP staining and incubated together with osteoclasts precursor cell
      line Raw 264.7 in 96 well plate. After 9 d, 10 micromol/L ALN, 10(-5) g/L rhOPG
      Fc, 10 micromol/L ALN + 10(-5) g/L rhOPG-Fc, 5 micromol/L ALN + 5 x 10(-6) g/L
      rhOPG-Fc were added to these coculture systems. Osteoblasts cultured without the
      drugs mentioned above served as controls. TRAP stain positive cells counting and
      cortical bone pit formation counting were preformed in the following the 3rd and
      7th d. RESULTS: SDS-PAGE and Western blot showed that molecular weight of the
      expressed protein was about 55 KD, and it could reach specifically with anti-IgG
      antibody. Many multi-nuclear TRAP stain positive cells were found in the
      coculture control group after 9 d incubation, and proved to be mature osteoclasts
      by TRAP stain. In the 3rd and 7th d after the addition of rhOPG-Fc, ALN or both,
      TRAP stain positive cells counting and cortical bone pit formation counting
      decreased significantly in the rhOPG-Fc, ALN or both groups than in the control
      group, and the combine group (10(-5) g/L rhOPG-Fc + 10 micromol/L ALN) decreased
      most significantly when compared with rhopG-FC or ALN single. CONCLUSIONS: rhOPG
      Fc can decrease the number of osteoclasts and inhibit their function. The
      combination of both rhOPG-Fc and ALN shows the significant inhibition effect on
      mature osteoclasts.

PMID- 16083596
TI  - [Surgical treatments of preoperative unsuspected gallbladder carcinoma].
AB  - OBJECTIVE: To explore the surgical treatment of preoperative unsuspected
      gallbladder carcinoma (UGC) and its prognosis. METHODS: Eighteen patients of UGC
      admitted in our hospital from January 1996 to December 2003 were analyzed
      retrospectively. The clinicopathological characters and surgical treatment of UGC
      patients were compared with the preoperative diagnosed gallbladder carcinoma
      (DGC) patients admitted in the same period. The cumulative survival rate of the
      patients received radical resection in two groups was analyzed by Kaplan-Meier
      method. RESULTS: The serous layer was not invaded by tumor in 10 patients of UGC
      group (55.5%, 10/18), while the serous layer invaded and regional lymph node
      metastasis were detected in 39 patients of DGC group (90.7%, 39/43). Radical
      resection rate was 72.2% (13/18) in UGC group and 39.5% (17/43) in DGC group, and
      5-year survival rates in those with radical resection were 54.6% and 23.5%,
      respectively (chi(L)(2) = 16.33, P < 0.01). Compared with the patients underwent
      palliative operation, the patients with radical resection has a longer median
      survival time (43.3 months vs 10.5 months, chi(L)(2) = 31.10, P < 0.01).
      CONCLUSIONS: The prognosis of UGC is better than that of DGC generally.
      Reoperation for UGC should be performed as soon as possible, and the prognosis
      can be improved by radical resection.

PMID- 16083597
TI  - [Experience of diagnosis and treatment of carcinoma arising from congenital
      biliary duct cyst].
AB  - OBJECTIVE: To summarize the experience in diagnosis, prevention and treatment of
      carcinoma arising from congenital biliary duct cyst. METHODS: The clinical and
      pathological data of 185 patients with congenital biliary duct cyst admitted to
      Chinese PLA General Hospital were analyzed retrospectively. RESULTS: Among 185
      patients, twenty-seven cases had carcinomas arising from congenital biliary duct
      cyst, and the frequency of malignant transformation was 14.6%, which closely
      related to the age (P < 0.001). The incidences of malignancy for different age
      groups were: 0 for 0-9 age group, 5.1% for 0-19, 9.1% for 20-29, 16.2% for 30-39,
      26.7% for 40-49, 33.3% for 50-59, and 50% for over 60, respectively. Six patients
      had the history of cyst-enterostomy. Abdominal pain, fever, jaundice and weight
      loss were the main clinical manifestations. Abdominal ultrasonography, CT, MRI or
      magnetic resonance cholangiopancreatography, MRCP and endoscopic retrograde
      choledochopancreatography (ERCP) were the main diagnostic methods. For twenty
      patients (74.1%), a definite diagnosis was made preoperatively, but it's hard to
      make an early diagnosis. Nine patients (33.3%) underwent curative resection.
      CONCLUSIONS: Congenital biliary duct cyst is a premalignant lesion, and the
      incidence of carcinogenesis increases remarkably with age. The most effective
      method for prevention of carcinogenesis in choledochal cyst is complete excision
      of choledochal cyst during childhood, and the prognosis is poor for patients with
      biliary malignancy.

PMID- 16083598
TI  - [Analysis of the relation between surgery and prognosis of hilar
      cholangiocarcinoma].
AB  - OBJECTIVE: To explore the prognosis factors of hilar cholangiocarcinoma, and
      investigate the relation between operative procedure and prognosis of it.
      METHODS: A retrospective cohort study was investigated in 198 patients with hilar
      cholangiocarcinoma, who were treated in our hospital from December 1997 to
      December 2002. There were 117 males and 81 females. The age ranged from 27 to 81
      years old with a mean of 56. Jaundice (94.5%), pruritus (56.6%) and abdominal
      pain (33.8%) were the main present symptoms. According to Bismuth-Corlette
      classification, there were 14 type I cases, 19 type II cases, 12 type IIIa cases,
      15 type IIIb cases, 112 type IV cases and 26 unclassifiable cases. One hundred
      and forty four cases received open operative treatment, and the others only were
      treated with endoscopic approach (including ERBD or EMBE 21 cases, ENBD 31 cases)
      or percutaneous transhepatic cholangiodrainage (2 cases). Tumor resection was
      performed on 120 cases with a resection rate of 83.3%, included radical resection
      59 cases (41.0%). Twenty-four cases underwent paunched biliary exploration and
      drainage. RESULTS: The Cox's regression model analysis showed that occupation,
      preoperative maximum total serum bilirubin level, operative procedure and
      postoperative adjuvant radiation affected postoperative survival significantly,
      but gender, age, choledocholithiasis, hepatitis, preoperative serum CA19-9 level,
      Bismuth-Corlette type, histopathologic grading and postoperative chemotherapy
      were not significant prognostic factors. The postoperative survival of biliary
      drainage group, palliative resection group and radical resection group, which
      statistically differed pairwise. Between ERBD or EMBE group and palliative
      resection group, there was no statistical difference. So was between ERBD or EMBE
      group and biliary drainage group, or between ENBD group and biliary drainage
      group. The survival differed statistically between ERBD or EMBE group and ENBD
      group. CONCLUSIONS: Operative procedure was the most important prognosic factor
      of hilar cholangiocarcinoma, radical resection still was the primary measure to
      cure and long term survival. For irresectable hilar cholangiocarcinoma, the
      effect of ERBD or EMBE could not be considered to be worse than that of open
      operative treatment.

PMID- 16083599
TI  - [Expression of Smad4 and transforming growth factor-beta1, transforming growth
      factor-beta receptor II in cholangiocarcinoma tissue and its biological
      significance].
AB  - OBJECTIVE: To study the expression of Smad4 and transforming growth factor
      beta(1) (TGFbeta(1)), transforming growth factor-beta receptor II (TGFbetaRII) in
      cholangiocarcinoma tissue and its relationship with the biological behaviour and
      prognosis of the disease. METHODS: The expressions of Smad4, TGFbeta(1) and
      TGFbetaRII were detected by immunohistochemical technique in 47 specimens of
      cholangiocarcinoma and the normal bile duct tissue adjacent to the tumor. The
      expressions of Smad4, TGFbeta(1) and TGFbetaRII were compared with the clinical
      stages and pathological grades of the patients. RESULTS: The expression of
      TGFbeta(1) was positive in 36 cholangiocarcinomas (76.6%), which was higher than
      that in the normal tissue adjacent to the lesion. The positive expressions of
      Smad4 and TGFbetaRII were 14 (29.8%) and 28 (59.6%) in the carcinoma tissues,
      respectively (P < 0.05). The expression of TGFbeta(1) was related to the clinical
      stage, metastasis of lymph node and liver of the tumor (P < 0.05), but not with
      the histological grade (P > 0.05). There was positive correlation between
      TGFbetaRII expression and the clinical stage (P < 0.05), but no correlation
      between the TGFbetaRII expression and histological grade or metastasis of lymph
      node and liver (P > 0.05). The expression of Smad4 was associated with the
      histological grade, clinical stage and metastasis of lymph node and liver (P <
      0.05). CONCLUSIONS: The expressions of Smad4, TGFbeta(1) and TGFbetaRII correlate
      with the histological grading, clinical staging and metastasis of the lymph node
      and liver in cholangiocarcinoma. Combined detection of Smad4, TGFbeta(1) and
      TGFbetaRII may be helpful in the determination of the malignant degree and the
      prognosis of this disease.

PMID- 16083600
TI  - [The relationship between the C589T polymorphism of IL-4 gene and
      cholelithiasis].
AB  - OBJECTIVE: To investigate the relationship between IL-4 gene polymorphism and
      cholelithiasis in Chinese population. METHODS: Polymerase chain reaction combined
      with restriction enzyme digestion was used to detect the polymorphism of IL-4
      gene in 81 cholecystolithiasis, 41 patients with biliary duct stone. RESULTS:
      There were no significant differences of the IL-4 gene polymorphism genotypes and
      alleles between 81 cholecystolithiasis patients (CC11.1%, CT34.6%, TT54.3%;
      C28.4.7%, T71.6%). There were significant differences of the IL-4 gene
      polymorphism genotypes and alleles between 41 patients with biliary duct stone
      (CC48.8%, CT36.6%, TT14.6%; C67.1%, T32.9%). CONCLUSIONS: The C589T polymorphism
      of IL-4 gene was not associated with cholecystolithiasis patients in Chinese, but
      was related to patients with biliary duct stone in Chinese.

PMID- 16083602
TI  - [Effect of external vavuloplasty of deep vein in the treatment of chronic venous
      insufficiency of lower extremity].
AB  - OBJECTIVE: To verify the role and effect of external vavuloplasty in the
      treatment of chronic venous insufficiency (CVI) of lower extremity. METHODS:
      Thirty patients with CVI of bilateral lower extremities were enrolled to accept
      surgical management of vein systems. Both limbs of each patient were randomized
      into two groups respectively according to the operating style. One limb was given
      external vavuloplasty of the superficial femoral vein and surgery of superficial
      venous system (group A), the another limb was only given the surgery of
      superficial venous system (group B). The effect comparison between both limbs of
      each patient and two groups by color duplex scanning, color doppler velocity
      profile (CDVP), air plethysmography and CEAP score system one month and 3 years
      after operation. RESULTS: All 60 limbs of 30 cases were CEAP C(2)-C(4) with
      degree III reflux (Kistner's method) in the deep veins confirmed by color duplex
      scanning and venography. In 1 month and 3 years after surgery, all the indexes of
      the limb in the group A were dramatically improved compared with those of the
      limbs in the group B. The average value of venous reflux degree, reflux volume,
      and venous filling index (VFI) had significant difference between the two groups
      (P < 0.001). In 3 years after surgery, there was significant difference between
      the two groups on ejective fraction (EF)and residual volume fraction (RVF) (P <
      0.05) and CEAP clinical score (P < 0.001). CONCLUSION: External vavuloplasty of
      deep vein may reduce the reflux volume of the affected deep vein and improve the
      valve function, and can result in better outcomes when combined with surgery of
      the superficial venous system.

PMID- 16083603
TI  - [Strategies for handling the insufficiency of the proximal landing zone during
      endovascular thoracic aortic repair].
AB  - OBJECTIVE: To discuss two strategies for handling the insufficiency of the
      proximal landing zone (PLZ) during endovascular thoracic aortic repair. METHODS:
      Ten patients underwent endovascular repair (EVR) in the thoracic aorta in one
      year. Nine patients had DeBakey type III aortic dissection aneurysm (ADA), and
      one had descending thoracic aortic aneurysm (DTAA). The PLZ, defined as the
      distance from the origin of the left subclavian artery (LSA) to the primary entry
      tear of the dissection or the proximal aspect of DTAA, was measured less than 15
      mm in all instances by contrast-enhanced CT scan and digital subtraction
      angiography. The preliminary carotid-carotid and left carotid-subclavian bypass
      combined with EVR was employed in the DTAA and 3 ADA cases, and the EVR with the
      intentional coverage of the LSA without the preliminary bypass in the rest 6 ADA
      patients. RESULTS: The technical success was achieved in all instances. The case
      of DTAA died of the hemispheric cerebral infarction and subsequent multiple
      system organ failure, albeit the uneventful recovery from the prior cervical
      reconstruction. Dizziness occurred in 2 patients (ADA) after the EVR with the
      intentional bypass-absent coverage of the LSA, but noticeably resolved after the
      intravenous administration of mannitol for 4 to 5 days. No neurological deficits
      or limb ischemia developed perioperatively or during the follow-up range from 3
      to 12 months. And complete thrombosis of the thoracic aortic false lumen and
      enlargement of the true lumen were revealed on CT at 3 months in all 9 patients
      with ADA. CONCLUSIONS: Both the adjunctive surgical bypass and the intentional
      bypass-absent coverage of the left subclavian artery appear feasible in handling
      the insufficiency of the proximal landing zone during the endovascular thoracic
      aortic repair. It can expand the EVR applicability in management of DeBakey type
      III ADAs and DTAAs.

PMID- 16083604
TI  - [To study the effects of local co-transfection vascular endothelial growth
      factor165 and tissue-type plasminogen activator genes on inhibiting intimal
      hyperplasia after operation injury artery in rabbits].
AB  - OBJECTIVE: To observe the effects of local co-transfection vascular endothelial
      growth factor165 (VEGF165) and tissue-type plasminogen activator genes on
      inhibiting intimal hyperplasia and restenosis in rabbits artery after operation
      injury and possible mechanisms. METHODS: Micrology operation injury was used to
      establish the model of intimal injury of right external iliac artery in rabbits.
      To select 120 male New Zealand rabbits and were randomly divided into 3 groups (n
      = 40, in each group): Group A (physiological brine control group), Group B
      (pBudCE4.1 group), Group C (pBudCE4.1/VEGF165-tPA group). The vas-wall of
      micrology operation injury were infused respectively physiological brine,
      pBudCE4.1 and pBudCE4.1/VEGF165-tPA transfection solution by micro-injector. Each
      group were divided into 5 subgroups (n = 8, in each subgroup) randomly according
      to the sacrifice times (2 d, 1 week, 2 week, 4 week and 8 week after operation).
      The injured vascular specimen were harvested for pathology test, electric
      microscopy study, reverse transcription-PCR examining and immunochemistry
      detecting. RESULTS: The intimal area and narrow ratio of vases in Group C at
      every time point after operation were significantly lessened than that in Group A
      and Group B (P < 0.01). The narrow ratio of vases in Group C at 8 week after
      operation were decreased respectively by 57.9% and 59.0% than that in Group A and
      B. The expression of VEGF165 mRNA in Group C were increased significantly than
      that in Group A and B at every time point after operation (P < 0.01), the
      expression reached the peak at 1 week and continued to 4 week after operation.
      Immunohistochemical identified that tPA positive cell in Group C were
      significantly increased than that in Group A and B (P < 0.01) at every time point
      after operation. CONCLUSION: Local co-transfection VEGF165 and tPA genes could
      restrain intimal hyperplasia and restenosis of vas, which lay a foundation for
      future multi-gene therapy of vascular intimal hyperplasia.

PMID- 16083605
TI  - [Single or staged endovascular stent-graft repair for aortic dissection with
      multi-tears].
AB  - OBJECTIVE: To evaluate the single or staged endovascular stent-graft repair for
      aortic dissection with multi-tears. METHODS: The stent-grafts were inserted
      through the femoral artery to seal the tears of dissection. RESULTS: Between
      January 2001 and June 2004, 8 patients with aortic dissection underwent stent
      graft placement. There were 5 tears in one patient, 4 tears in two patients, 3
      tears in two patients and 2 tears in three patients. There were 11 tears located
      at descending thoracic aorta, 11 at abdominal aorta and 4 at iliac artery. Six
      patients underwent operation in single stage, and 2 in staged maneuver. Total 23
      stent-grafts were used, including 20 straight type grafts and 3 bifurcated
      grafts. Placement of the stent-graft was technically successful in all patients.
      Follow-up with CT or MRA examination after 3, 6, 12 and 24 months postoperatively
      showed the dissection disappeared with thrombosis in the false lumen, no endoleak
      occurred. All patients survived to present. CONCLUSION: Single or staged
      endovascular stent-graft repair is a promising, safe and effective procedure for
      aortic dissection with multi-tears.

PMID- 16083606
TI  - [Experimental study on preparation of decellularized artery vascular graft matrix
      and explantation of carotid artery allografts].
AB  - OBJECTIVE: To set up a new process to access the preparation of decellularized
      artery grafts. And to evaluate the feasibility of decellularized artery
      allografts was evaluated. METHODS: This study compared the effects of four
      extraction chemicals [1% t-octyl-phenoxypolyethoxyethanol (Triton X-100), 1% tri
      (n-butyl) phosphate (TnBP), and 1% sodium dodecyl sulfate (SDS) and trypsin
      (0.125, 0.25%) on thoracic artery vascular for 24 h (except trypsin for 2 h). At
      the base of it, a four-step process, including hypotonic, hypertonic solutions
      and combining with 1% Triton X-100 and 1% SDS detergents, were performed in
      rabbit thoracic artery vascular. Histological examination, tensile tests and
      expanding-burst tests were done on the samples. The decellularized carotid artery
      allografts were transplanted in other rabbits. RESULTS: Treatment with 1% SDS or
      1% Triton X-100 for 24 h could remove most cells with retention of near normal
      structure. A four-step process could remove all cells with the extracellular
      matrix well conserved. The pulling mechanical properties and burst pressure of
      decellularized carotid artery were similar to the control. The decellularized
      carotid artery allografts (diameter of 2 mm) were patent at explanting up to 2
      months. CONCLUSIONS: The acellular artery vascular graft matrix is well prepared
      with four-step process including detergents, such as TritonX-100, SDS without
      compromising the graft structure or mechanical properties significantly. The
      carotid artery allografts (diameter of 2 mm) decellularized by the process are
      patent at explanting up to 2 months.

PMID- 16083609
TI  - [The diagnosis and therapy of subclinical pituitary adenoma apoplexy].
AB  - OBJECTIVE: To investigate the clinical features, diagnosis and treatment in
      patients with subclinical pituitary adenoma apoplexy (SPAA). METHODS: A
      retrospective analysis of all operated patients with SPAA was performed. There
      were 50 male and 80 female patients, ranging from 16 to 65 years (average 39
      years). Endocrinological hormones were measured in all patients pre- and post
      operatively, and pituitary imaging was obtained by CT scan, MRI or both. RESULTS:
      Transsphenoidal surgery was achieved in 89 patients, and transcranial surgery was
      achieved in 41 patients. There was no operative mortality. PRL adenomas were the
      most common tumor type (56.2%). SPAA usually occurred in patients with big or
      giant adenomas (97%). Hypertension and diabetes mellitus were the possible
      predisposing factors. Postoperative follow-up ranged from 0.5 to 6 years (mean
      3.2 years). Tumor recurrence happened in 8 patients. Only 12 patients required
      radiotherapy with tumor residual (4 cases) and recurrence (8 cases) after
      surgery. Long-term thyroid or steroid hormone replacement was necessary in 25%
      and 20% of patients, respectively, and long-term desmopressin therapy was
      necessary in 1% of patients. CONCLUSIONS: The incidence of SPAA was higher than
      acute pituitary apoplexy. PRL adenomas are the most common tumor type. MRI is the
      best investigative modality of choice. Transsphenoidal surgery is a safe and
      effective method. The rate of long-term endocrinological hormones replacement
      therapy of SPAA is lower than acute pituitary apoplexy, and the prognosis of SPAA
      is better than acute pituitary apoplexy. Radiotherapy is indicated if the tumor
      residual or recurrence are confirmed by CT or MRI after surgery.

PMID- 16083610
TI  - [Clinicopathologic characteristics and microsurgical treatment of glioma of
      limbic and paralimbic system].
AB  - OBJECTIVE: To explore the features of the clinical manifestations, imaging,
      pathology and microsurgery on the patients with gliomas of limbic and paralimbic
      system. METHODS: The clinical data of 28 patients with gliomas of limbic and
      paralimbic system were analyzed respectively. RESULTS: Seizure was the most
      common symptom, presented in 24 cases. CT scans showed hypodensity in 19 cases
      and isodensity in 9 cases. MRI scans were achieved in 23 cases, showing
      hypointense signal on T(1)WI and hyperintense signal on T(2)WI. Total resection
      was achieved in 19 cases, subtotal in 6 cases and partial in 3 cases. All
      patients had excellent postoperative recovery, except 5 patients who developed
      temporary frontal aphasia and 6 patients who developed contralateral hemiplegia.
      The patients had a postoperative follow-up ranging from 6 months to 5 years, and
      23 cases still survived. CONCLUSION: High-resolution CT and MRI may reveal the
      size, location, confines and sharp demarcation of the tumors. Gliomas can be
      microsurgically removed with considerable results.

PMID- 16083611
TI  - [Research on relationship of survivin gene expression with malignant
      proliferation and apoptosis of brain glioma].
AB  - OBJECTIVE: To investigate the expression level of inhibitor of apoptosis protein
      survivin gene in human brain glioma and its role in malignant proliferation and
      antiapoptosis of brain glioma. METHODS: Eighty-three cases of brain glioma
      specimen was chosen, protein expression of survivin and proliferating cell
      nuclear antigen (PCNA) was investigated by immunohistochemistry streptavidin
      biotin complex (SABC) method, the immunoreactivity score (IRS) of survivin and
      the proliferative index (PI) were counted. Apoptotic cells were screened by TdT
      mediated dUTP-biotin nick-end labeling (TUNEL) method, and the apoptotic index
      (AI) of brain glioma was calculated. RESULTS: The survivin IRS, PI and AI of
      brain glioma were 3.8 +/- 3.9, (28.4 +/- 19.5)% and (1.0 +/- 0.8)% respectively,
      and all of them were elevated with the increase of pathological grade of brain
      glioma (P < 0.01 for all). PI in survivin positive group was significantly higher
      than that in survivin negative group (P < 0.01), and PI was positively correlated
      with survivin IRS (r = 0.740, P < 0.01). There was no significant difference
      between AI in survivin positive group and that in survivin negative group (P >
      0.05), however, AI was negatively correlated with survivin IRS (r = -0.307, P <
      0.01). CONCLUSIONS: Survivin is overexpressed in brain glioma, and which may play
      important roles in malignant proliferation and antiapoptosis of brain glioma.

PMID- 16083612
TI  - [Establishment of maca mulatta model of resuscitation after selective cerebral
      ultra-deep hypothermic blood flow occlusion].
AB  - OBJECTIVE: To study the feasibility of resuscitation after selective cerebral
      ultra-deep hypothermia and blood flow occlusion. METHODS: Ten 4-10 year-old maca
      mulattas were divided into 3 groups: four-vessel occlusion group, two-vessel
      occlusion group and identical temperature perfusion group. MRI were examinated
      before and after operation, the vital signs and the hemodynamical parameters were
      observed during the experiment, neurological deficient evaluation was performed
      after operation. RESULTS: In all of the ten monkeys, the hemodynamical parameters
      of two-vessel occulation were steady during the operation, and all of them lived
      after filling 60 minutes. MRI were normal after operation, and the function of
      neurological deficient scale was normal. The others of identical temperature
      perfusion group and four-vessel occlusion group were not resuscitation after
      filling 60 minutes and died. CONCLUSION: Monkey could resuscitate from selective
      cerebral ultra-deep hypothermia and blood flow occlusion of bilateral common
      carotid artery in 60 minutes.

PMID- 16083618
TI  - [Surgical treatment of severe cicatricial anastomotic stricture after
      esophagectomy for esophageal and cardiac cancer].
AB  - OBJECTIVE: To review the experience of the surgical procedure in the treatment of
      postoperative severe cicatricial anastomotic stricture for esophageal cancer and
      cardiac cancer. METHODS: Twenty-four cases with severe anastomotic strictures and
      dysphagia after esophagectomy underwent second operation. The anastomosis was
      opened by two small transverse incisions about 1-2 mm above and below the
      anastomotic line. The esophageal and gastric walls were half opened. Then the
      circular cicatricial tissue was partially removed. The re-anastomosis was
      performed with a one layer, intermittent technique. RESULTS: The second
      operations were successfully completed in 24 cases, cervical anastomotic leakage
      happened in 1 case and no operative mortality. All cases were followed up for 2-3
      years. All patients can eat soft and common diet smoothly. No anastomotic
      strictures were found and the quality of life was significantly improved.
      CONCLUSION: The second surgery with partial removal of the narrow cicatricial
      ring and reanastomosis for postoperative severe anastomotic stricture after
      esophagectomy is feasible, and the result is satisfactory.

PMID- 16083619
TI  - [Surgery for upper or middle thoracic esophageal carcinoma after gastrectomy].
AB  - OBJECTIVE: To evaluate the surgical treatment and technical key-points of upper
      or middle thoracic esophageal carcinoma in patients with history of gastrectomy.
      METHODS: Eighty-six patients with upper or middle thoracic esophageal carcinoma
      after previous gastrectomy received surgical treatment between 1980 and 2004.
      Among them, tumor location was in middle thoracic esophagus in 50 patients, in
      upper thoracic esophagus in 31 and cervical esophagus in 5. Postoperative
      pathological staging was stage I in 16 patients, stage IIa in 62, stage IIb in 5
      and stage III in 8. The interval between gastrectomy and the diagnosis of
      esophageal carcinoma ranged from 2 to 22 years. Surgical procedures included
      esophagectomy and reconstruction with nonreversed gastric tube in 2 patients and
      reversed gastric tube in 3. The esophagus was reconstructed with short segment of
      colon in 5 patients and long segment of colon in 74. Two cases underwent
      jejunostomy only. RESULTS: Seventy-six patients (88%) were treated with curative
      intent. Seven patients (8%) received palliative surgery. Postoperative
      complication rate was 12% (10/86). One patient died of multiple organ dysfunction
      syndrome (MODS). Sixty-seven patients were followed up, the 1-, 3-, 5-year
      survival rates were 84% (56/67), 57% (38/67) and 22% (15/67), respectively.
      CONCLUSIONS: Surgical treatment is the first choice for esophageal cancer
      patients after gastrectomy although the procedures are complicated. The surgery
      should be considered as a reliable therapeutic modality because of favorable
      patient prognosis. The replacement with colon is recommended for those patients.

PMID- 16083620
TI  - [Expressions of E-cadherin in non-small cell lung cancer and it correlation with
      prognosis].
AB  - OBJECTIVE: This study was to clarify E-cadherin expressions in non-small cell
      lung cancer (NSCLC) and its correlation with patients' prognosis. METHODS: Tissue
      microarrays (TMAs) containing specimens from 365 different NSCLC were
      constructed, covering all stages and almost all histological types of this
      disease. Slides were immunohistochemically stained with antibodies against E
      cadherin. Expression pattern of the protein was analyzed with relation to the
      clinicopathological. Correlations of the results with patients' overall survival
      were also examined. RESULTS: Immunohistochemical staining revealed that E
      cadherin protein was localized mainly on membranes and the cytoplasm of NSCLC
      tumors cells. Reduced E-cadherin expression was evident in 32.1%. Reduced E
      cadherin expression significantly correlated with lymph nodes metastasis (chi(2)
      = 16.430, P = 0.001), histological dedifferentiation (chi(2) = 9.243, P = 0.010)
      and advanced clinical stage (chi(2) = 9.421, P = 0.024). There was no significant
      difference in E-cadherin expression between squamous cell carcinoma and
      adenocarcinoma. E-cadherin reduced expression correlated with a poor prognosis (P
      < 0.0001) in univariate analysis. Multivariate analysis showed a significantly
      lower survival probability for patients with reduced E-cadherin (P < 0.001), and
      E-cadherin was an independent prognostic factor for survival of NSCLC patients.
      CONCLUSIONS: It suggests that dysfunction of E-cadherin has an important impact
      in the progression of lung cancer. As an independent prognostic factor,
      expression of E-cadherin can predict outcome of different group, together with
      conventional prognostic factors, and subsequently make appropriate management.

PMID- 16083621
TI  - [Left atrial plication for left atrium associated with mitral valve disease].
AB  - OBJECTIVE: To evaluate the effects of left atrial plication (LAP) in patients
      with giant left atrium (GLA) associated with mitral valve disease. METHODS:
      Twenty-three patients with left atrial diameter (LAD) over 8.0 cm were enrolled.
      All cases underwent valve replacement and LAP between November 1993 and November
      2004 were studied retrospectively. According to New York Heart Association (NYHA)
      classification, 15 belonged to class III, 8 to class IV. Mitral valve
      replacements were performed in 18 patients (mechanical valve in 17 and biological
      valve in 1), double value replacement in 5, tricuspid valve plasty (TVP) in 15,
      atrial fibrillation radiofrequency ablation in 2. RESULTS: Low output syndrome
      happened in 3, respiratory failure in 2. The early death was in 3 cases
      (operative mortality 13%). The causes of death were: heart failure in 2 cases and
      stroke in 1. LAD was decreased significantly in patients after operation.
      CONCLUSIONS: LAP has considerably beneficial effects on improvement of
      postoperative respiratory and cardiac function, reducing operative mortality.
      Atrial fibrillation radiofrequency ablation is effective in patients with GLA
      associated with valve disease. It may be recommended for patients with GLA during
      mitral valve surgery, especially for patients with LAD > 8.0 cm.

PMID- 16083622
TI  - [The endovascular repair of aortic dissection: early clinical results of 178
      cases].
AB  - OBJECTIVE: To discuss the safety, feasibility, efficacy and problems of
      endovascular repair for aortic dissection. METHODS: From June, 1998 to Dec, 2004,
      178 aortic dissections were treated by stent-grafts, including 76 acute cases and
      102 chronic cases, 19 cases with Stanford A and 159 cases with Stanford B. Under
      local or general anesthesia, every stent-graft was deployed at the proper
      position of first tear entry through femoral artery under X-ray fluoroscopic. The
      changes of hemodynamic in true and false lumen, visceral and limbs blood supply
      were investigated after operation. RESULTS: 10 cases combined with left common
      carotid artery or left subclavian artery or hepatic artery and superior
      mesenteric artery bypass. 36 left subclavian arteries were covered simultaneously
      without bypass and the average blood pressure of left brachial artery was (61.6
      +/- 23.7) mm Hg. The stent-grafts were deployed above thoracic 8 in 159 cases and
      below thoracic 8 in 19 cases. This group included 3.4% 30-day death rate, 12.9%
      endoleak rate after deployment, and without misplace of stent grafts, migration,
      rupture, conversion to open surgery and paraplegia complication. The average
      operation time 1.5 h (0.5-4.3 h), blood loss 140 ml (30-500 ml), movement recover
      time 1.8 d (0.5-21.0 d), food recover time 1.5 d (0.5-9.0 d). The true lumen
      blood supply in most of damaged visceral arteries were improved. Follow up
      between 1 month to 76 months, the endoleak rate was 6.4% one month later.
      CONCLUSION: The endovascular repair is a safe, efficacy and feasible method to
      aortic dissection. The long term results keep in follow up.

PMID- 16083623
TI  - [Experiences of retroperitoneal approach for aortoiliac reconstruction].
AB  - OBJECTIVE: To summarize experiences of aortoiliac reconstruction through
      retroperitoneal approach. METHODS: Twenty-eight patients underwent
      retroperitoneal aortoiliac reconstructions, including aortic aneurysmectomy with
      graft replacement, aortic endarterectomy with patch angioplasty, thoraco
      abdominal aortic bypass, resection of retroperitoneal mass with ilio-femoral
      bypass, iliac aneurysmectomy with aorto-external iliac artery bypass, removal of
      aortoiliac foreign body, common iliac endarterectomy, aorto (ilio)-femeral bypass
      and common ilio-femo-popliteal bypass. Drainage tubes were placed
      retroperitoneally in 24 cases. RESULTS: All operations in this group were
      successful without perioperative death. The volume of intra-operative bleeding
      was 100-400 ml (mean 240 ml). Blood transfusion were employed in 2 cases.
      Retroperitoneal drainage was 50-170 ml (mean 85 ml). Naso-gastric tubes were
      removed 28 h on average after operation. All patients recovered uneventfully
      except that cardiac insufficiency, stress ulcer and retroperitoneal hematoma were
      present in 3 patients respectively. Twenty-two patients were followed up from 3
      months to 2.5 years. One patient died of AMI 2 years after operation. One patient
      receiving ilio-femo-popliteal bypass was found to have occlusion of femo
      popliteal segment of prosthetic graft. One patient developed brain hemorrhage 1.5
      years postoperatively. All the other followed-up patients were living well.
      CONCLUSION: Retroperitoneal approach, not violating the peritoneal cavity, offers
      certain physiological advantages associated with minimal disturbance of
      gastrointestinal and respiratory function, thereby decreasing respiratory
      complications and postoperative ileus, avoiding intra-abdominal adhesions with
      their attendant risk of early and late small bowel obstruction. It proved to be a
      simple and safe alternative for surgical treatment of aortoiliac diseases.

PMID- 16083624
TI  - [Clinical analysis of 1018 cases of coronary artery bypass grafting].
AB  - OBJECTIVE: To analyze retrospectively 1018 patients who underwent coronary artery
      bypass grafting surgery (CABG) in order to summarize surgical techniques and
      clinical outcome. METHODS: From 1997 through 2004, data of same surgeon for 508
      patients who underwent conventional coronary artery bypass surgery on pump
      (CCABG) and 510 patients who underwent off-pump CABG (OPCAB) were collected and
      analyzed retrospectively. Eight hundred and fifty-two patients had unstable
      angina, 582 patients were over 60 years old (57.2%) and 784 patients had
      concomitant diseases including valve lesion, hypertension, diabetes, myocardial
      infarction, left ventricular aneurysm with septal defect, stroke, chronic
      obstructive pulmonary diseases, renal failure and cancer. A hundred and fifty-six
      patients had left main stem (LIMS) stenosis and 671 patients, triple-vessel
      disease. RESULTS: Total mortality was 0.39% (4-case death) and morbidity, 1.6%
      (sternal dehiscence, stroke and mediastinitis). The grafts per patient with CCABG
      and OPCAB were 3.3 +/- 0.6 vs. 2.5 +/- 0.4. Left internal mammary artery use was
      93.8% of the patients, 29 patients were implanted intra-aortic balloon pump
      intraoperatively. Follow-up was 4 months to 7 years. CONCLUSIONS: Scientific
      surgical strategies, excellent surgical techniques and improvement of cardiac
      anesthesia and cardiopulmonary bypass make the mortality and morbidity decrease
      significantly, CABG surgery is safe and effective in patients with coronary
      artery disease.

PMID- 16083627
TI  - [The treatment choice of solitary kidney complicated with complex calculi report
      of 42 cases].
AB  - OBJECTIVE: To investigate the therapeutics of complex calculi in solitary kidney,
      and to improve the effect and safety of treatment. METHODS: Experiences in the
      treatment of 42 patients were summarized. All patients were with mould or
      multiple calculi, 8 cases were complicated with ureter calculi, and 6 cases were
      hospitalized because of obstructive anuria. The patients with mould calculi
      received extracorporal shock wave lithotripsy (ESWL) prior to percutaneous
      nephrolithotomy (PCNL). While the patients with multiple calculi received PCNL
      prior to ESWL. Some cases were treated by lithotripsy. RESULTS: Thirty-six cases
      (86%) were cured by ESWL combined with PCNL. Eleven cases received lithotripsy
      during PCNL. The 6 cases with obstructive anuria recovered in 12 hours after
      emergent ESWL or lithotripsy; 6 cases (14%) underwent open operation because of
      deformity or obstruction in renal pelvis and ureter; 2 cases have to keep
      nephrostomy because of repeated infection. Followed up 6-18 months, 38 cases
      (86%) keep good kidney function; 5 cases (14%) had renal insufficiency; 4 cases
      (11%) reoccurred calculi. CONCLUSIONS: The therapeutics of ESWL combined with
      PCNL may clear complex calculi of solitary kidney effectively and safe. It is
      necessary to take emergent ESWL in renal obstructive calculi cases. And the
      patients with lower ureter obstructive calculi may take lithotripsy first. It is
      proper to choose open operation on the patients with deformity of renal pelvis or
      obstruction of ureter.

PMID- 16083628
TI  - [Treatment of hyperhomocysteinemia and endothelial dysfunction in renal
      transplant recipients with vitamin B].
AB  - OBJECTIVE: To study the effect of vitamin B on treatment of hyperhomocysteinemia
      and endothelial dysfunction in renal-transplant recipients. METHODS: Thirty-six
      stable hyperhomocysteinemic renal-transplant recipients were randomly assigned to
      vitamin treatment (group A, n = 18, folic acid 5 mg/d, vitamin B(6) 50 mg/d,
      B(12) 1000 microg/d) or controlled group (group B, n = 18) for 6 months. All
      subjects underwent assessment of levels for creatinine, creatinine clearance,
      average pressure, total cholesterol, triglyceride and fasting homocysteine.
      Endothelial function was evaluated using high-resolution vascular ultrasound.
      RESULTS: The levels of homocysteine markedly decreased in group A [(13 +/- 4)
      micromol/L vs (20 +/- 5) micromol/L, t = 5.3, P < 0.01] after treatment, whereas
      no significant changes were observed in group B. In group A, endothelium
      dependent [(12 +/- 5)% vs (9 +/- 5)%, t = 2.9, P < 0.01] and independent [(18 +/-
      4)% vs (12 +/- 5)%, t = 3.4, P < 0.01] vasodilatation responses significantly
      increased after treatment, no significant changes were observed in group B.
      Endothelium dependent [(9 +/- 6)%, t = 2.8, P < 0.01] and independent [(12 +/-
      5)%, t = 3.5, P < 0.01] vasodilatation responses of group A were significantly
      lower than that of group B after treatment. CONCLUSIONS: Vitamin B
      supplementation can reduce the levels of homocysteine and improve the endothelial
      function in hyperhomocysteinemic renal-transplant recipients.

PMID- 16083629
TI  - [Primary pigmented nodular adrenocortical disease report of 5 cases].
AB  - OBJECTIVE: To study the pathology, diagnostic and therapeutic method of primary
      pigmented nodular adrenocortical disease (PPNAD). METHODS: The data of 5 cases of
      PPNAD were analyzed retrospectively. Among the 5 cases, 2 were male and 3 were
      female. The range of age was from 12 to 53 years. All the 5 cases had symptoms of
      Cushing syndrome. The diagnose depended on the results of endocrine exams,
      ultrasound, CT, MR and pathological reports. All patients received operation of
      unilateral adrenalectomy. The therapeutic effects were determined by post
      operative results, which concluded clinical symptoms and endocrine exams.
      RESULTS: The follow-up time was from 4 months to 3 years. All patients' symptoms
      of Cushing syndrome were relieved in 6 months after operation. The endocrine exam
      was normal in one case and obvious improved in the other four cases. Up to now,
      one patient drop out of the follow-up, the other 4 cases had no evidence of
      recurrence. CONCLUSION: PPNAD is a rare type of Cushing syndrome. Diagnose
      depends on endocrine exams and pathological results. Operation is the effective
      method for the disease.

PMID- 16083630
TI  - [Association between single-nucleotide polymorphisms in estrogen receptor beta
      gene and risk of prostate cancer].
AB  - OBJECTIVE: This study was undertaken to investigate the relationship of some
      single nucleotide polymorphisms (SNPs) of estrogen receptor beta (ERbeta) with
      the risk of prostate cancer (CaP). METHODS: The allele, genotype distribution in
      an association study with case-control samples involving 40 CaP cases and 86
      unrelated healthy male subjects was analyzed. In these individuals, three
      upstream regions of the proximal ER promoter SNPs (rs3829768, rs1271572,
      rs3841304) and exon 7 SNP (rs1256049) were analyzed by directly sequencing
      amplified PCR products of genomic DNA. RESULTS: Four polymorphisms were
      identified. The rs3841304 was excluded from further analysis because of
      significant deviation from the Hardy-Weinberg equilibrium. The genotype and
      allele frequency of rs3829768 (A/G) and rs1271572 (C/A) in the upstream region of
      proximal promoter were significantly decreased in the CaP cases versus control (P
      < 0.01). CONCLUSIONS: Our study suggests that this disease of interest is highly
      associated with rs3829768 (A/G) and rs1271572 (C/A) in CaP cases. CaP, prostate
      cancer; ERalpha, estrogen receptor alpha; ERbeta, estrogen receptor beta; SNP,
      Single nucleotide polymorphisms; betaERKO, ERbeta knockout; PIN, prostatic
      intraepithelial neoplasia; HWE, Hardy-Weinberg equilibrium; NRE, Negative
      Regulatory Element.

PMID- 16083641
TI  - Suicidal high falls.
AB  - There are few data on committing suicide by jumping from a height. Information on
      suicidal high falls in southeast Scotland was prospectively gathered over 7 years
      (1992-1998). Data sources included ambulance, police, hospital and forensic
      records. Injuries sustained were scored according to the Abbreviated Injury
      Scale, generating Injury Severity Scores (ISS). Sixty-three individuals (50
      males), appeared to have committed suicide by falling from a height. The
      backgrounds were diverse, but 44 individuals had known previous psychiatric
      illness, 18 having attempted suicide before. The most common locations were high
      bridges, with two accounting for 23 deaths (37%). Only nine individuals (14%)
      reached hospital alive. ISS range was 16-75, including 22 scores of 75. These
      individuals had a total of 24 injuries acknowledged to be unsurvivable,
      comprising 10 thoracic aortic ruptures, eight massive brain/brainstem injuries,
      four cardiac injuries, and two high spinal cord transections. The high rate of
      prehospital death reflects the heights of the falls and consequent major
      injuries. Prevention of suicide is acknowledged to be difficult - these results
      suggest that hospital treatment of injuries sustained has little to offer in
      terms of reducing the death rate from suicidal high falls.

PMID- 16083642
TI  - Early adolescent suicide: a comparative study.
AB  - A study was undertaken of suicides in children and adolescents aged 16 years and
      under in South Australia, (Australia), and in San Diego County (USA) from January
      1985 to December 1997. In South Australia there were 48 cases of youth suicide,
      representing 2% of the total number of 2251 suicides over that time. There were
      34 males and 14 females (age range 13 to 16 years; mean = 15.3 years), with 22
      hangings (46%), six gunshot wounds (13%), five train deaths (10%), four drug
      overdoses (8%), four jumping deaths (8%), three self immolations (6%), three
      carbon-monoxide inhalations (6%) and one electrocution (2%). In San Diego County
      there were 70 cases, representing 1.6% of the total number of 4492 suicides.
      There were 48 males and 22 females (age range 11 to 16 years; mean = 14.7 years),
      with 41 gunshot wounds (59%), 21 hangings (30%), six drug overdoses (9%), and two
      jumping deaths (3%). Preferred methods of suicide differed between the two areas,
      with significantly more gunshot suicides in San Diego compared to South
      Australia. The methods of suicide also differed in South Australia from older age
      groups, with more hangings, jumping deaths and self immolations, and fewer
      firearm and carbon monoxide inhalation deaths. Suicides in adolescents under the
      age of 17 years in both populations were, however, rare, with no demonstrable
      increase in numbers over the time of the study.

PMID- 16083643
TI  - A workload survey of police surgeons in Darlington, UK showing recent changes and
      detailed work patterns in 1998.
AB  - This paper gives an accurate picture of the police surgeon workload in the town
      of Darlington for the year 1998, and is compared with a similar workload survey
      done 5 years ago in 1993. The number of cases seen in 1998 shows an increase of
      142% compared with 5 years ago, and various explanations are given as to the
      possible causes of this significant change. The pattern of call-outs for the time
      of day and the busiest nights of the week clearly shows the peak demands for our
      services in the evenings and especially Friday and Saturday nights. The breakdown
      showing the reason for attendance indicates the significant rise in drug addicts
      seen with associated drug-driving assessments. Examination for CS spray are
      compared with a correspondingly small number of baton injuries and injuries to
      police officers. This type of information could be used to introduce police
      surgeon recruits to the pattern of work that awaits them. Planning and budget
      implications could be more accurately predicted, and the figures could be used to
      compare with other areas for those police surgeons who also keep records.

PMID- 16083644
TI  - beta -amyloid precursor protein positive axonal bulbs may form in non-head
      injured patients.
AB  - Since the early 1980s axonal bulbs staining positively for beta-amyloid precursor
      protein (betaAPP) have been used as a marker of diffuse axonal injury (DAI), bulb
      formation been attributed to shearing forces generated during rotational
      acceleration/deceleration head injury. This study draws attention to the
      observation that they may form in the absence of a head injury and, thus, axonal
      injury cannot be assumed to result from mechanical injury alone. Out of 20 cases
      with no history of head injury studied, which only showed evidence of neuronal
      hypoxic change, 11 (55%) showed variable positive staining for betaAPP in a
      similar anatomical distribution to that previously described for DAI. The role of
      hypoxia in the formation of axonal bulbs, as well as the possible role of betaAPP
      as an acute phase protein, are discussed. These observations further clarify the
      pattern and relationship between neuronal and axonal staining observed following
      a brain insult and emphasize the possible role of betaAPP as a neuroprotective
      protein.

PMID- 16083645
TI  - Volatile substance use in sexual asphyxia.
AB  - A 38-year-old man was found dead in bed dressed in female clothing with a mouth
      gag, handcuffs and bindings around the genitals and limbs. A respirator was also
      covering the mouth and nose. There were no suspicious circumstances and a
      diagnosis of death due to sexual asphyxia was made. Following the subsequent
      discovery of bottles of chloroform in the bedroom, head space analysis of blood
      confirmed the presence of chloroform, with a blood level of 33 mg/L. Death was,
      therefore, attributed to a combination of chloroform toxicity and upper-airway
      obstruction. Headspace analysis with follow-up quantitation may, therefore, be a
      useful adjunct to the investigation of such cases when devices such as
      respirators or gas masks are found with the body.

PMID- 16083646
TI  - Spontaneous human combustion: a sometimes incomprehensible phenomenon.
AB  - Several cases of human combustion, the cause of which was not evident, have been
      described over the last few centuries. There are three intriguing elements to
      such cases. Firstly, although the body is destroyed, the immediate surroundings
      are left almost intact. Secondly, there is often no visible source of heat that
      might have started the fire. Thirdly, sometimes bodies are not completely
      destroyed, certain parts being perfectly preserved, adjacent to others that are
      reduced to a state of ashes.

PMID- 16083647
TI  - Assessment in police custody of individuals under the influence of alcohol with
      co-morbid psychiatric disorders.
AB  - Individuals with a diagnosis of excessive alcohol intake are commonly encountered
      in police custody. These individuals have a high incidence of co-morbid
      psychiatric disorders. The Epidemiological Catchment Area (ECA) Study reported
      that 37% of alcoholics have a co-morbid mental disorder.(1)It is, therefore,
      important that individuals in custody who have a history of excessive alcohol
      intake are adequately assessed, in order to identify such co-morbid disorders so
      that appropriate management is implemented. Assessment of all individuals in
      police custody should include: To date, little has been written on how such
      assessments should be carried out in police custody. This paper discusses the
      presentation of psychiatric disorders in individuals with a history of excessive
      alcohol intake and suggests how they should be assessed in custody. A subsequent
      issue of the journal will include an article discussing the management of such
      individuals.

PMID- 16083648
TI  - Stabbing to right temple with partial knife blade retention: differentiating stab
      from slash wound.
AB  - This case was presented in May 1999 at the APS Conference in Jersey, Channel
      Islands and the WPMO Conference in Vancouver, BC, Canada, August 1999.

PMID- 16083650
TI  - Response from authors.

PMID- 16083649
TI  - Ethanol metabolism in patients with liver cirrhosis.
AB  - Aspects of human metabolism of ethanol are reviewed with the main focus on the
      rate of ethanol clearance from blood in patients suffering from liver cirrhosis.
      Studies in humans and experimental animals do not support the notion of a slower
      rate of ethanol metabolism in patients with liver cirrhosis compared with those
      with normal liver function. The rate of ethanol disappearance from blood in
      healthy non-alcoholic subjects falls within the range 9-20 mg/dL/h and there is
      no compelling evidence to suggest that this should be much different in cirrhotic
      patients.

PMID- 16083652
TI  - Correspondence.

PMID- 16083651
TI  - Re: Letter to the Editor - Interpretation of Section 7(3)(c) of the Road Traffic
      Act 1988.

PMID- 16083653
TI  - Continuing Education Programme - Victorian Institute of Forensic Medicine and
      Department of Forensic Medicine, Monash University.
AB  - Given the increasing requirement of the courts for forensic experts to engage in
      ongoing education, a continuing education programme was developed in forensic
      medicine at the Victorian Institute of Forensic Medicine to cater for both
      clinicians and pathologists. The programme consists of a series of cases which
      are circulated several times per year. All are actual cases and are reflective of
      the types of presentations experienced in forensic medicine. Each case includes
      relevant and appropriate details/findings and may include photographs. A series
      of questions follow which are answered usually in short-answer format. The
      answers are returned and correlated by a review panel, and a commentary with the
      response outcome is distributed to all those involved. The cases presented here
      are selected from this programme.

PMID- 16083654
TI  - Cocaine metabolism in hyperthermic patients with excited delirium.
AB  - The half-life of cocaine in clinical experiments has been reported to range from
      60 to 90 min. It has been previously suggested that elevated temperature may
      accelerate the metabolism of cocaine. However, there is no clinical data to
      indicate the presence of hyperthermia like that seen in excited delirium alters
      the half-life of cocaine. We report the results of half-life determinations from
      serial cocaine concentrations in two patients with excited delirium. Both
      patients presented to the emergency department with classic findings of excited
      delirium that included hyperthermia, agitation, and cardiovascular aberrations.
      One patient died despite aggressive therapeutic intervention. Cocaine and
      metabolite concentrations were determined by an extractive alkylation mass
      spectrometry procedure. Presenting cocaine concentrations in patient 1 and
      patient 2 were 0.387 and 0.266 mg/L respectively. Results from pharmacokinetic
      modeling of the serial concentrations show that the half-life of cocaine was not
      significantly accelerated, despite the presence of hyperthermia. Data from these
      two cases provide further evidence that catastrophic reactions to cocaine are
      independent of amount or route of administration, and that the metabolism of
      cocaine, at least in these patients, was not altered by hyperthermia.

PMID- 16083655
TI  - Drugs of abuse in urine of young adult drivers involved in road accidents in a
      Paris suburb (1996).

PMID- 16083656
TI  - A profile of deaths in custody in Victoria, 1991-96.
AB  - In Victoria, all deaths in custody are investigated and a coronial inquest is
      held. The findings are entered into a data base held at the Victorian Institute
      of Forensic Medicine. Utilizing this data base, all listed cases of deaths in
      custody during the 6-year period, January 1991-December 1996, were reviewed. The
      deceased's age, sex, cause and mechanism of death and the custodial service under
      which they were held at the time of death were correlated. During the 6-year
      period, there was a total of 96 deaths (90 male, six female) ranging in age from
      15-77 years. Of all the cases, 45 occurred whilst in police custody, 30 under
      corrective services and 21 involved non-custodial corrections. There were 31
      accidental deaths, 29 suicides, 17 natural deaths, and 18 police shootings.
      Excluding police shootings, 42 deaths involved the presence of drugs or alcohol,
      either as a direct cause of death or as a contributory factor. Drug toxicity
      alone was implicated in 28 deaths. Deaths from unnatural causes remains the major
      cause of death of persons in custody. An awareness of these causes must assist in
      developing mechanisms to further reduce fatalities in this setting.

PMID- 16083657
TI  - Delayed death owing to blunt cardiac injury.
AB  - Two cases of blunt myocardial injury to the region of the anterior descending
      branch of the left coronary artery causing death are described. In one case,
      direct injury appeared to have resulted in myocardial infarction, whereas in the
      other, cardiac arrhythmia (possibly secondary to coronary artery spasm) was
      implicated. Although apparently uncommon, deaths following blunt injury to the
      coronary arteries may cause death, but are difficult to predict and prevent.

PMID- 16083658
TI  - Defining fitness for interview.

PMID- 16083660
TI  - Fractures of the hyoid bone and laryngeal cartilages in suicidal hanging.
AB  - A prospective study of neck trauma associated with suicidal hanging was
      undertaken at the Forensic Science Centre, Adelaide over a 3-year period from
      July 1996 to June 1999. There were a total of 40 cases of suicidal hanging with
      an age range of 17-74 years (average = 35 years; M:F = 33:7). Fractures of neck
      structures were identified in 19 cases (47.5%) and were more common in older
      victims and males. Nine victims had only thyroid cartilage fractures (22.5%),
      four victims had only fractures of the hyoid bone (10%), and six victims had
      fractures of both the hyoid bone and thyroid cartilage (15%). No fractures of the
      cricoid cartilage or cervical spine were demonstrated. Potentially confusing
      issues encountered in the assessment of possible fractures of neck structures
      included cases where there was congenital absence of the greater horn of the
      thyroid cartilage, where accessory nodules of cartilage were present in the
      posterior margin of the thyrohyoid membrane, and where there had not yet been
      bony fusion of the cartilaginous joints between the greater horns and body of the
      hyoid bone.

PMID- 16083661
TI  - A new method of recording clinical forensic evidence.
AB  - Digital photography is a practical tool, useful for the recording of clinical
      forensic evidence.

PMID- 16083662
TI  - Creating a DIN to tackle drug-related deaths in the community.
AB  - Brighton and Hove has one of the highest rates of drug-related deaths in the UK.
      The deceased commonly have had contact with a number of organizations isolated
      from each other. The aim of this study was to explore aspects of drug addiction
      in Brighton as the first stage in the creation of a local Drug addiction
      Intervention Network (DIN) and to make recommendations about improving the
      effectiveness of medical contacts so that modifiable risk factors could be
      addressed appropriately and consistently. The coroner's records of the drug
      related deaths in 1998 for Brighton and Hove were cross-referenced with
      computerized records of the Accident & Emergency department of the local hospital
      and the police station. Of the 36 drug misusers who died during the year, most
      were male, mean age 34 years. Alcohol was a common comorbid finding. Seventy
      eight per cent were known to the A&E department and 62% had been arrested locally
      during 1997 or 1998. Such retrospective data can only give limited information.
      We, therefore, performed a prospective survey. It was carried out by the forensic
      medical examiner (FME) in 1997-1998, interviewing 41 arrestees to give a profile
      of the criminally involved drug misusers. With the information obtained, the A&E
      doctors and FMEs were able to review the medical advice given and establish a
      protocol for the transfer of severely intoxicated arrestees.

PMID- 16083663
TI  - Management in police custody of individuals under the influence of alcohol with
      co-morbid psychiatric disorders.

PMID- 16083664
TI  - Misleading results of ethanol analysis in urine specimens from rape victims
      suffering from diabetes.
AB  - We report appreciably high concentrations of ethanol (82 and 102 mg/dL) in
      specimens of urine collected from two victims of date rape. Both girls (aged 15
      and 18 years) suffered from diabetes mellitus, but adamantly denied drinking any
      alcohol before or after the incident. The presence of glycosuria and high risk of
      fungal infections in female diabetics suggests that ethanol was produced in vitro
      by fermentation after voiding. Making a routine test for sugar in the urine and
      ensuring that the sampling tubes contain sufficient sodium or potassium fluoride
      to inhibit glycolysis are recommended practices. A specific marker for post
      sampling synthesis of ethanol might also be used such as the 5HTOL/5HIAA ratio.

PMID- 16083665
TI  - The value of the size of foramen magnum in sex determination.
AB  - Sex determination in unidentified skeletons is not always easily and correctly
      performed by a non-specialist without formal training in forensic anthropology.
      In explosions, warfare and other mass disasters like aircraft crashes,
      identification may be extremely complicated because of skeletal fragmentation.
      The aim of the present study was to determine whether the area of the foramen
      magnum was a useful criterion for the sex determination in fragmented skulls. In
      a total of 219 skeletons (170 males and 39 females) the longest and the shortest
      diameter of the foramen magnum was measured; the area within was determined using
      the mean of the diameters as the radius for calculation. The mean of foramen
      magnum area was significantly different (909.91 +/- 126.02 mm2 in males, 819.01
      +/- 117.24 mm2 in females homogeneous variance, Student's t-test: 4.11 P< 0.001).
      However, the correlation coefficient between the areas of foramen magnum and sex
      was 0.27. The results confirmed that the mean foramen magnum area in females is
      lower than in males. However, the area of foramen magnum is not a very useful
      indicator for sex identification and can be used only under some circumstances as
      a supportive finding.

PMID- 16083666
TI  - Registration of Forensic Medical Practitioners. The expression of a standard.
AB  - The Council for the Registration of Forensic Practitioners (CRFP) has been set
      up, in the wake of high profile miscarriages of justice, to promote confidence in
      forensic practice in the UK. Its Governing Council consists of users,
      practitioners and lay members. It will publish a register of competent
      practitioners; set standards for them; and deal with practitioners whose fitness
      to practise is questioned. Registration will be based on an assessment of
      competence by peer review. Revalidation will follow every 4 years (the General
      Medical Council's new proposals involve a 5-year revalidation). There are
      significant advantages in these proposals for forensic medical practitioners over
      and above existing regulatory arrangements.

PMID- 16083667
TI  - Drug related deaths amongst Glasgow city hostel dwellers.
AB  - The problems of homelessness and drug misuse are every day issues encountered in
      today's society. Over the past 2 years the number of hostel residents overdosing
      within their rooms in the city of Glasgow was shown to increase. Approximately
      three-quarters of deaths involved heroin, of which 56% also involved at least one
      benzodiazepine. This paper demonstrates a dearth in the literature relating to
      drug misuse amongst the homeless population, highlighting an area in need of
      address by the appropriate authorities.

PMID- 16083668
TI  - Child neglect or tragic misadventure?
AB  - The body of a 2-month-old baby was found inside the pram where he had been left
      overnight. Initial assessment of the event by a paramedic unit seemed to indicate
      foul play, based on the presence of a prominent linear pressure mark on the
      child's scalp and face. Thorough police and medicolegal investigation cleared the
      suspect and disclosed that the death resulted from accidental positional
      asphyxia, related to a faulty mechanism of the pram. We advise that when
      examining sudden unexpected death of children, forensic investigators should be
      aware of the potential hazards associated with baby accessories.

PMID- 16083669
TI  - Victims of violence: an Asian scenario.
AB  - The term 'violence' is difficult to define. Aggressive behaviour with actual use
      of physical force may result in some form of physical and emotional trauma to an
      individual and this could be considered as violence against the person. The
      trauma may range from minimal physical injury to death. It is also relevant to
      note that in some jurisdictions if members of the law enforcement agencies with
      appropriate authority resort to certain acts of 'violence' for lawful purposes,
      then such acts of violence may be excluded from this category. However, if the
      law enforcement personnel exceed their limits of authority, or resort to various
      unacceptable and unauthorized methods of violence, then certainly such acts will
      become violence against the person. In today's context the word violence has
      expanded to encompass many issues, besides the usual physical violence such as
      assault. Rape, child sexual abuse, other forms of sexual abuse, non-accidental
      injury to children, battered wife, assault in custody, torture, victims of war,
      civil unrest and ethnic violence are all considered under 'violence'. While
      general violence is almost endemic in many countries, assault in custody,
      torture, political and ethnic violence are serious problems in some of the
      developing world. In these countries, particularly, the law enforcement agencies
      and other unlawful groups who are backed by politicians may inflict politically
      motivated violence against its citizens. In such cases attempts are often made to
      cover up such crimes. Forensic physicians and forensic pathologists who examine
      these cases may be placed in difficult positions at times owing to various
      'pressures' being brought upon them to issue 'favourable' reports. On the other
      hand there is also a general dearth of suitably trained forensic physicians and
      forensic pathologists in many of these countries. Medical officers without any
      training in forensic medicine often undertake the examination of victims of
      violence, both living and fatal cases. Lack of training makes them more
      vulnerable to political and other forms of 'pressure'. The objective of this
      article is to highlight some of the common problems that are encountered,
      particularly in developing countries.

PMID- 16083670
TI  - The medical management in police custody of alcohol dependent detained persons.
AB  - The author devised a simple postal questionnaire which was sent to all of the UK
      members of the Association of Police Surgeons, requesting information about their
      management in police custody of alcohol dependent persons detained by the police.
      The questionnaire and the results are presented. The results are analysed. The
      detention by the police of alcohol dependent patients is dangerous as these
      patients are at risk of sudden death. Some of the relevant literature is
      considered and then a suggested management scheme for such a situation is
      proposed.

PMID- 16083671
TI  - Unusual motor vehicle suicides.
AB  - A review was undertaken of cases in which motor vehicles were used to commit
      suicide. While the most common methods involved carbon monoxide toxicity or the
      sustaining of multiple injuries, three unusual cases were found involving: (i)
      hanging from a car seat belt, (ii) self immolation inside a car, and (iii)
      setting up a crash situation. The latter two cases were used as a backup to drug
      overdose. Problems that may occur in determining the manner of death are
      described.

PMID- 16083672
TI  - Guidance for doctors on the assessment of mental health for the purpose of
      recommending on appropriate adult under PACE.
AB  - This is a new feature for the Journal. A case report is described and those with
      a particular interest in the field are asked to comment. Further submissions are
      invited and welcomed.

PMID- 16083674
TI  - Re: Naik P. C., Brownell L. W., Management in police custody of individuals under
      the influence of alcohol with co-morbid psychiatric disorders. Journal of
      Clinical Forensic Medicine 2000; 7: 139-143.

PMID- 16083675
TI  - Carbon-monoxide poisoning in young drug addicts due to indoor use of a gasoline
      powered generator.
AB  - We report six fatal cases of unintentional carbon-monoxide poisoning which
      occurred in a house occupied by young people. The source of carbon monoxide was a
      gasoline-powered generator. For all victims, an external body examination was
      carried out and blood and urine samples collected. Blood carboxyhaemoglobin
      (COHb) was performed using an automated visible spectrophotometric analysis.
      Blood-alcohol level quantification was performed using gas chromatography and
      drug screening in urine was performed by a one-step manual qualitative
      immunochromatography (Syva Rapid test, Behring Diagnostics Inc.) for
      benzoylecgonine (the main metabolite of cocaine in urine), morphine, 11-nor
      Delta(9)-THC-9-COOH (cannabinoids) and d-methamphetamine. In all victims the COHb
      value was as high or higher than 65%. No alcohol was found in blood samples, but
      urine samples were positive for methamphetamine, cocaine and cannabis in five
      cases and for opiates in one case. In four victims, the urine sample was positive
      for at least three drugs. The availability and accuracy of rapid toxicological
      screening is an important tool for the medical examiner at the immediate scene of
      a clinical forensic examination.

PMID- 16083676
TI  - Gastric distension, cerebral palsy and unexpected death.
AB  - Two cases of unexpected death from massive gastric dilatation in individuals with
      severe spastic quadraparesis aged 14 and 20 years, respectively, are reported.
      Spontaneous rupture of the stomach occurred in one case. Predisposing factors to
      gastric dilatation associated with cerebral palsy include autonomic neuropathy,
      neuromuscular incoordination, air swallowing and malposition of the stomach.
      Death may be due to compromise of respiratory function caused by lung compression
      by the dilated stomach, or to peritonitis with sepsis. Acute gastric dilatation,
      with or without rupture, should be considered a potential cause of unexpected
      death in individuals with severe mental and physical disabilities.

PMID- 16083677
TI  - Rape: an Asian perspective.
AB  - Rape is one of the fastest growing violent crimes in many parts of the world.
      Rape laws have been amended in most countries in an attempt to cope with the
      proliferation of this crime. Even though the legal definition of rape and the
      procedural laws have been amended, rape remains a serious problem in both the
      developed and developing nations. In some countries the offence of rape carries
      severe punishment sometimes even the death sentence. In many jurisdictions the
      term 'sexual penetration' is being used instead of 'sexual intercourse'. Sexual
      penetration includes sexual intercourse, anal intercourse, cunnilingus, fellatio
      or any other intrusions involving any part of a human body or of any object into
      the genital or anal opening of a person's body. In many countries rape and other
      sexual offences have been replaced with a series of gender neutral and graded
      offences with appropriate punishments. Medical examination can provide
      independent, scientific, corroborative evidence that may be of value to the court
      in arriving at a judgement. Doctors should have a clear understanding of
      different rape laws in order to apprectiate the various issues involved. Special
      knowledge, skill and experience are essential to conduct a good-quality medical
      examination. There is a dearth of trained forensic physicians in many Asian
      countries. However, managing a rape victim (survivor) goes for beyond proving the
      case in a court of law. There should be an adequate rehabilitation programme
      available to the victims to help them cope.

PMID- 16083678
TI  - Continuing education programme - Victorian Institute of Forensic Medicine and
      Department of Forensic Medicine, Monash University.
AB  - Given the increasing requirement of the courts for forensic experts to engage in
      ongoing education, a continuing education programme was developed in forensic
      medicine at the Victorian Institute of Forensic Medicine to cater for both
      clinicians and pathologists. The programme consists of a series of cases which
      are circulatged several times per year. All are actual cases and are reflective
      of the types of presentations experienced in forensic medicine. Each case
      includes relevant and appropriate details/findings and may include photographs. A
      series of questions follow which are answered usually in short-answer format. The
      answers are returned and correlated by a review panel, and a commentary with the
      response outcome is distributed to all those involved. The cases presented here
      are selected from this programme.

PMID- 16083679
TI  - The Southwark Police Surgeon Study 1978-1997: methods, sample and description.

PMID- 16083680
TI  - Differing approaches to the identification of Munchausen by Proxy Syndrome
      (MBPS): a case of professional training or role of experiental exposure.
AB  - Much recent research recognises that a multidisciplinary team approach is best to
      manage Munchausen by Proxy Syndrome (MBPS), an extreme manifestation of
      factitious disorder by proxy (FDBP). Generally described as fabricating illness
      symptoms in a child to serve the adult caretaker's attention seeking needs,
      identification of the disorder remains problematic. Various relevant
      professionals differ in their emphasis and vary in their knowledge of the
      condition which in turn can inhibit collaborative investigation and intervention.
      Reasons for these difficulties are described together with a rationale for better
      interagency co-operation, not least because the outcome in some cases is the
      death of the child. The present paper discusses the implications of professional
      training in identification of MBPS and the value of previous exposure to cases in
      increasing likelihood of detection. An empirical study is described that presents
      working models used by different professionals to identify cases of MBPS (n=12).
      Analysis of qualitative interview material by means of a multidimensional scaling
      procedure revealed no clear grouping in terms of occupational specialism, rather
      commonalities of approach appeared related to previous experience with MBPS. The
      range of salient factors elicited was used to devise a parsimonious screening
      checklist intended for use by different professional groups. Finally, future
      research in terms of investigating psychometric profiles of MBPS child abusers
      and demonstrating the utility of the checklist for use by multidisciplinary teams
      in early detection and subsequent management of MBPS is discussed.

PMID- 16083681
TI  - Death due to malathion poisoning.
AB  - Malathion is a commonly available insecticide with relatively low toxicity. A
      study was undertaken in South Australia over a 20-year period to assess the
      characteristic features of deaths associated with malathion. A total of 5 cases
      were found, in each of which exposure to malathion had been intentional. The male
      to female ratio was 2:3 with an age range of 32 to 80 years (mean = 57 yr). In
      four cases malathion had been ingested and in one case death had resulted from an
      intravenous injection of insecticide. Ingestion of large volumes of malathion was
      associated with contamination of the mortuary due to postmortem regurgitation in
      at least one case. The study also demonstrates that suicides due to malathion
      poisoning were uncommon in thispopulation, representing only 0.2% of the 3,202
      suicides recorded at the Forensic Science Centre over the 20year period.

PMID- 16083682
TI  - Safe detection and retrieval of drugs concealed internally.
AB  - This is a new feature for the Journal. A case report is described and individuals
      with a particular interest or experience in the field have been asked to comment.
      Further submissions are invited and welcomed.

PMID- 16083684
TI  - Mental illness and the need for an appropriate adult.

PMID- 16083685
TI  - Forensic urinalysis of drug use in cases of alleged sexual assault.
AB  - The results of 3303 analyses of urine samples, collected in an independent
      testing programme from individuals who claimed to have been sexually assaulted
      and believed that drugs were involved, were examined in detail. Of the samples
      provided, 2026 (61.3%) proved positive for one or more substances. Alcohol,
      either alone or in combination with other drugs, was by far the commonest
      substance found, being present in 1358 samples (67.0% of positives). Cannabis was
      the second most prevalent drug, present in 613 samples, (30.3% of positives).
      Detailed examination of the testing results does not support the contention that
      any single drug, apart from alcohol, can be particularly identified as a 'date
      rape' drug. Rather, the alleged sexual assaults may often take place against a
      background of licit or recreational alcohol or drug use, where alcohol and other
      drugs are frequently taken together. The extensive forensic database examined
      here does not support the concept of a commonly occurring 'date rape' scenario,
      in which the victim's drink is covertly 'spiked' with a tablet, capsule or powder
      containing a sedative-hypnotic. This research highlights the need for the early
      collection of forensic samples in cases of alleged sexual assault. Law
      enforcement agencies and health professionals should establish guidelines and
      procedures to ensure that appropriate forensic samples (blood and urine) are
      collected in a timely manner following allegations of possible drug mediated
      sexual assault.

PMID- 16083686
TI  - Lesions that simulate gunshot wounds - further examples II.
AB  - A variety of postmortem and antemortem defects may be misinterpreted as gunshot
      wounds. In this paper, we present an additional series of lesions that simulate
      gunshot wounds. We briefly discuss each case, emphasizing various aspects of the
      scene investigation, clinical correlation and autopsy that are important in each
      case.

PMID- 16083687
TI  - Diagnostic issues in unusual asphyxial deaths.
AB  - Upper airway occlusion may be due to a variety of causes and may result from
      accidents, suicides or homicides. Underlying natural diseases may also predispose
      to lethal choking episodes. A series of nine cases is reported to illustrate a
      range of circumstances that resulted in fatal upper airway compromise. These
      included suicide from upper airway obstruction due to an impacted blanket, and
      accidental deaths due to inhalation of soil, a rock, and a video cassette
      sticker. One death resulted from glottic obstruction due to a mucosal cavernous
      haemangioma, another from an enlarged tonsil, and two deaths were precipitated by
      underlying organic disease in the form of dementia and insulin-dependent diabetes
      mellitus. The manner of death was not clear cut in two cases where there was
      evidence of possible accidental death or suicide.

PMID- 16083688
TI  - Forensic investigations in Kosovo: experiences of the European Union Forensic
      Expert Team.
AB  - The international community has intervened ethnic hostilities in Kosovo, the
      Federal Republic of Yugoslavia. A team of Finnish forensic experts worked in
      December 1998 and January 1999 in Kosovo under the mandate of the European Union.
      The team investigated human remains from three locations of alleged ethnic
      violence. Concerning the events in Klecka, Volujak and Racak, the International
      Criminal Tribunal for the former Yugoslavia received documents of great gravity.
      The standard methods of forensic pathology were complemented with radiological,
      forensic odontological, physical anthropological and molecular genetic
      investigations.

PMID- 16083689
TI  - Bacteriological skin and subcutaneous infections in injecting heroin users
      relevance for custody.
AB  - Forensic medical examiners, custody nurses and police not infrequently come into
      physical contact with injecting heroin users whose injection sites maybe
      infected. Karch evaluated published reports on bacteriological findings at
      infected injection sites in drug users in 1996. Studies were then 10 years out of
      date. Recent concern has been about unexplained deaths in injecting heroin users,
      partly attributed to toxins produced by Clostridium novyii, Clostridium
      perfringens (welchii) and Clostridium botulinum. In response to this epidemic
      Lambeth, Southwark and Lewisham Health Authority (London, UK) urged investigation
      and treatment of injection site infection in heroin users within their area;
      circularising police stations and general practices with an official notice. In
      response, I followed up and treated in general practice 35 injecting heroin users
      with injection site infection presenting as detainees at two South London police
      stations. All swabs taken had a 48 hour incubation for anaerobic bacteria. At
      audit, no spore forming anaerobes were found. Just under 25% had non spore
      forming anaerobes such as bacteroides. Just over 50% had staphylococci in the
      injection site infection. Just under 20% had streptococci, half of which were
      beta haemolytic, a possible contact risk of infection being erysipelas,
      cellulitis, impetigo or conjunctivitis. No comparable studies were found but a
      study in New York in 1984 tabulated bacteriological findings of soft tissue
      infections in 29 hospitalised parenteral drug users. They found similar
      proportions of staphylococci, far more with streptococci, hardly any with non
      spore forming anaerobes and one case of spore forming anaerobic clostridium
      perfringens.

PMID- 16083690
TI  - An epidemiological study and determination of causes of traffic accident-related
      deaths in Tehran, Iran (during 2000-2001).
AB  - Traffic accidents are an important cause of traumatic death particularly in
      developing countries such as Iran. One of the most principal steps in prevention
      and control of traffic accident-related trauma and its deaths is having
      information about demographic characters of its victims and their cause of
      deaths. Our cross sectional study deals with all of the cases of traffic accident
      related deaths which were referred to the Tehran Legal Medicine Organization.
      This survey covers one year from March 20th, 2000 to March 24th, 2001. All the
      victims' files were studied. Number of traffic accident-related deaths were 2128
      (25% of all of cases which were referred to this centre for determination of
      cause of death). Male to female ratio was 4.1 to 1. Most of deaths have been
      between 21 and 30 years old (22.1%). Mean age was 39.4 year (SD: 21.9 yr).
      Seasonal variation was not seen. Twenty-seven percent of cases were died at the
      scene and 72.7% in hospital. The most common cause of death was head injury
      (49.8%), the other causes were multiple trauma (35%), internal bleeding and
      visceral laceration(11.1%), cervical spinal cord injury (1.9%), complications of
      trauma (1.6%) and others (0.6%), respectively. These findings were compared with
      other surveys and authors recommend some suggestions such as public education of
      traffic rules, obligatory use of seat-belts, wearing of crash-helmet, attention
      to preventable causes of death, etc.

PMID- 16083691
TI  - Shoulder-lap seat belts and thoracic transection.
AB  - While seat belt usage significantly decreases mortality and morbidity from
      traffic accidents, specific injuries may also occur. Two cases are described in
      adults where the wearing of three point restraints (shoulder-lap belts) in a
      serious high-speed vehicle accident resulted in fatal injuries to both a driver
      and a passenger. 'Mirror image' fractures of the sternum, rib cage and clavicles,
      with separation of the two halves of the rib cages and underlying trauma to the
      hearts and thoracic aortae resulted in death in both victims. Profound life
      threatening internal injuries may be caused by seat belts in the absence of
      significant cutaneous injury. The pattern of internal trauma can also be useful
      in determining whether a seat belt was worn at the time of the accident, and on
      which side of the vehicle the deceased was sitting.

PMID- 16083692
TI  - Upper airway occlusion by soil--an unusual cause of death in vehicle accidents.
AB  - Upper airway obstruction by soil is a rare cause of death in motor vehicle
      accidents. Four cases were found in a search of the records of the Forensic
      Science Centre in Adelaide, South Australia over a twenty-year period from
      January 1982 to December 2001. Case 1: A 68-year-old male driver died from sand
      inhalation after he was trapped in his vehicle following an accident. His mouth
      and upper airway were packed with sand. Case 2: A 33-year-old male pedestrian
      died from smothering after he had been knocked over and had his head pressed face
      down into sandy soil by a vehicle wheel. Case 3: A 12-year-old male passenger
      died from soil inhalation after the vehicle in which he was travelling rolled
      over and filled with soil. His mouth and upper airway were packed with soil. In
      these cases the victims had been trapped with the face covered in fine, or loose,
      soil or sand. In Case 4 a 41-year-old male passenger was ejected from a vehicle.
      He died from blunt chest trauma exacerbated by occlusion of the mouth and nose by
      soil. Careful scene descriptions are required in the assessment of such cases, in
      addition to evaluation of the relative contribution of injuries and asphyxia to
      the fatal episode.

PMID- 16083697
TI  - Mannose binding lectin gene polymorphisms confer a major risk for severe
      infections after liver transplantation.
AB  - BACKGROUND & AIMS: Infection is the primary cause of death after liver
      transplantation. Mannose binding lectin (MBL) is a recognition molecule of the
      lectin pathway of complement and a key component of innate immunity. MBL variant
      alleles have been described in the coding region of the MBL gene, which are
      associated with low MBL serum concentration and impaired MBL structure and
      function. The aims of our study were to establish the role of the liver in
      production of serum MBL and to evaluate the effect of MBL variant alleles on the
      susceptibility to infection after liver transplantation. METHODS: We investigated
      49 patients undergoing orthotopic liver transplantation. MBL exon 1 and promoter
      polymorphisms were determined in patients and in liver donors. MBL serum
      concentration was determined before and during 1 year after transplantation. The
      incidence of clinically significant infections during this period was assessed.
      RESULTS: Transplantation of MBL wildtype recipients with donor livers carrying
      MBL variant alleles resulted in a rapid and pronounced decrease of serum MBL
      levels. This serum conversion was associated with the disappearance of high
      molecular weight MBL. No indication for extrahepatic production of serum MBL
      could be obtained. The presence of MBL variant alleles in the MBL gene of the
      donor liver, but not in the recipient, was associated with a strongly increased
      incidence of clinically significant infections after transplantation.
      CONCLUSIONS: Serum MBL is produced by the liver under strong genetic control.
      After liver transplantation, the MBL genotype of the donor liver is a major risk
      determinant for life-threatening infections.

PMID- 16083698
TI  - Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of
      onset.
AB  - BACKGROUND & AIMS: Mutations in the mismatch repair genes cause hereditary
      nonpolyposis colorectal cancer (HNPCC) syndrome and convey high lifetime cancer
      risks for colorectal (CRC) and endometrial cancer. Currently, cancer risks for
      individuals with HNPCC are based on data from clinically ascertained families.
      The purpose of this study was to re-examine the penetrance in HNPCC using a
      comprehensive dataset from a geographically defined region. METHODS: A combined
      dataset of 70 HNPCC families ascertained by traditional high-risk criteria and by
      molecular screening comprising 88 probands and 373 mutation-positive family
      members was used. Statistical methods were modified survival analysis techniques.
      RESULTS: In mutation-positive relatives (excluding probands), the median age at
      diagnosis of CRC was 61.2 years (confidence interval [CI], 56.3-68.0 y). The
      lifetime risk for CRC was 68.7% (CI, 58.6%-78.9%) for men and 52.2% (CI, 37.6%
      66.9%) for women. Considering only probands, the median age at diagnosis of CRC
      was 44.0 years (CI, 41.0-46.3 y). Median age of onset of EC was 62.0 years (CI,
      55.9 y to an upper limit too high to calculate) with a lifetime cancer risk of
      54% (CI, 41.9%-66.1%). CONCLUSIONS: A markedly later age of onset for CRC at 61 y
      than previously reported (approximately 44 y) is suggested, resulting mainly from
      a more rigorous method of analysis in which all gene-positive individuals (both
      affected and unaffected with cancer) are considered. Lifetime cancer risks may be
      lower for CRC and endometrial cancer than presently assumed. If confirmed, these
      data suggest a need to alter counseling practices, and to consider HNPCC in older
      individuals than before.

PMID- 16083699
TI  - A comparison of the immunochemical fecal occult blood test and total colonoscopy
      in the asymptomatic population.
AB  - BACKGROUND & AIMS: The fecal occult blood test (FOBT) is recommended as a
      screening test for colorectal cancer, but there are few reliable studies on the
      accuracy of immunochemical FOBT. The aim of this study was to analyze the
      sensitivity of immunochemical FOBT and to compare the results with the findings
      from complete colonoscopy. METHODS: Asymptomatic adults underwent 1-time
      immunochemical FOBT and total colonoscopy simultaneously. The prevalence and
      location of colorectal neoplasia were determined by colonoscopy. The results of
      immunochemical FOBT and the colonoscopic findings were compared. RESULTS: Of
      21,805 patients, immunochemical FOBT was positive in 1231 cases (5.6%). The
      sensitivity of 1-time immunochemical FOBT for detecting advanced neoplasia and
      invasive cancer was 27.1% and 65.8%, respectively. In addition, the sensitivity
      for invasive cancer according to Dukes' stage showed 50.0% for Dukes' stage A,
      70.0% for Dukes' stage B, and 78.3% for Dukes' stages C or D. The sensitivity for
      detecting advanced neoplasia at the proximal colon was significantly lower than
      that detected in the distal colon (16.3% vs 30.7%, P = .00007). CONCLUSIONS:
      Although the screening of asymptomatic patients with immunochemical FOBT can
      identify patients with colorectal neoplasia to a certain extent, the sensitivity
      is relatively low and different according to the tumor location. Therefore,
      programmatic and repeated screening by immunochemical FOBT may be necessary to
      increase sensitivity for colorectal cancer detection.

PMID- 16083700
TI  - The perception of cancer risk in patients with prevalent Barrett's esophagus
      enrolled in an endoscopic surveillance program.
AB  - BACKGROUND & AIMS: Patients with Barrett's esophagus (BE) have a risk of
      esophageal adenocarcinoma of approximately 0.5% per year. Patients may have
      difficulty understanding this risk. This study assessed the perceived risk of
      cancer in patients with BE, and correlated their risk estimates with their health
      care use behaviors. METHODS: We performed a survey of patients with BE
      participating in an endoscopic surveillance program at 2 sites: a university
      teaching hospital and a Veterans' Administration hospital. A questionnaire also
      elicited their demographics as well as their sources of health information.
      Health care behaviors, including physician visits and endoscopic surveillance
      behaviors, were assessed. Patients were classified as either overestimators or
      nonoverestimators of risk. Characteristics of overestimators, as well as health
      care use patterns, were assessed. RESULTS: One hundred eighteen patients met
      entry criteria, and 92 (78%) completed all the questionnaires. Sixty-eight
      percent of patients overestimated their 1-year risk of cancer, with a mean
      estimated 1-year cancer risk being 13.6%. The lifetime risk also was
      overestimated by 38% of patients. Patients who overestimated risk were more
      likely to be Veterans' Administration medical center patients, have more
      symptomatic reflux, and were more likely to use the Internet to get health care
      information. There was no significant difference in physician visits between
      overestimators and nonestimators (1.2 visits per year vs 1.0, P = .20), nor in
      endoscopy use (5.7 endoscopies per 5-year period vs 5.0, P = .42). CONCLUSIONS:
      The majority of patients with prevalent BE participating in an endoscopic
      surveillance program overestimated their chances of developing adenocarcinoma of
      the esophagus. Efforts to improve education of such patients with BE are
      warranted.

PMID- 16083701
TI  - Differential expression of cannabinoid receptors in the human colon: cannabinoids
      promote epithelial wound healing.
AB  - BACKGROUND & AIMS: Two G-protein-coupled cannabinoid receptors, termed CB1 and
      CB2, have been identified and several mammalian enteric nervous systems express
      CB1 receptors and produce endocannabinoids. An immunomodulatory role for the
      endocannabinoid system in gastrointestinal inflammatory disorders has been
      proposed and this study sought to determine the location of both cannabinoid
      receptors in human colon and to investigate epithelial receptor function.
      METHODS: The location of CB1 and CB2 receptors in human colonic tissue was
      determined by immunohistochemistry. Primary colonic epithelial cells were treated
      with both synthetic and endogenous cannabinoids in vitro, and biochemical
      coupling of the receptors to known signaling events was determined by
      immunoblotting. Human colonic epithelial cell lines were used in cannabinoid
      binding studies and as a model for in vitro wound-healing experiments. RESULTS:
      CB1-receptor immunoreactivity was evident in normal colonic epithelium, smooth
      muscle, and the submucosal myenteric plexus. CB1- and CB2-receptor expression was
      present on plasma cells in the lamina propria, whereas only CB2 was present on
      macrophages. CB2 immunoreactivity was seen in the epithelium of colonic tissue
      characteristic of inflammatory bowel disease. Cannabinoids enhanced epithelial
      wound closure either alone or in combination with lysophosphatidic acid through a
      CB1-lysophosphatidic acid 1 heteromeric receptor complex. CONCLUSIONS: CB1
      receptors are expressed in normal human colon and colonic epithelium is
      responsive biochemically and functionally to cannabinoids. Increased epithelial
      CB2-receptor expression in human inflammatory bowel disease tissue implies an
      immunomodulatory role that may impact on mucosal immunity.

PMID- 16083702
TI  - Celiac disease and risk of adverse fetal outcome: a population-based cohort
      study.
AB  - BACKGROUND & AIMS: Studies of maternal celiac disease (CD) and fetal outcome are
      inconsistent, and low statistical power is likely to have contributed to this
      inconsistency. We investigated the risk of adverse outcomes in women with CD
      diagnosed prior to pregnancy and in women who did not receive a diagnosis of CD
      until after the delivery. METHODS: A national register-based cohort study
      restricted to women aged 15-44 years with singleton live born infants was used.
      We identified 2078 offspring to women who had received a diagnosis of CD (1964
      2001): 1149 offspring to women diagnosed prior to birth and 929 offspring to
      women diagnosed after infant birth. Main outcome measures were: intrauterine
      growth retardation, low birth weight (<2500 g), very low birth weight (<1500 g),
      preterm birth (<37 gestational weeks), very preterm birth (<30 gestational
      weeks), and caesarean section. RESULTS: Undiagnosed CD was associated with an
      increased risk of intrauterine growth retardation (OR = 1.62; 95% CI: 1.22-2.15),
      low birth weight (OR = 2.13; 95% CI: 1.66-2.75), very low birth weight (OR =
      2.45; 95% CI: 1.35-4.43), preterm birth (OR = 1.71; 95% CI: 1.35-2.17), and
      caesarean section (OR = 1.82; 95% CI: 1.27-2.60). In contrast, a diagnosis of CD
      made before the birth was not associated with these adverse fetal outcomes.
      CONCLUSIONS: Undiagnosed maternal CD is a risk factor for unfavorable fetal
      outcomes, but the risks are reduced when CD has been diagnosed. CD diagnosed
      prior to pregnancy does not constitute a great a risk as undiagnosed CD.

PMID- 16083703
TI  - Insulin-like growth factor-I and insulin are associated with the presence and
      advancement of adenomatous polyps.
AB  - BACKGROUND & AIMS: Insulin and insulin-like growth factor-I (IGF-I) affect
      proliferation, differentiation, and apoptosis and are potential risk factors for
      colorectal cancer (CRC). Visceral obesity, possibly via hyperinsulinemia, has
      also been linked to CRC risk. We evaluated the relationship of insulin, IGF-I,
      insulin-like growth factor binding protein (IGFBP) 3, and visceral adipose tissue
      (VAT) in subjects with adenomatous polyps, the precursor lesion of colorectal
      cancer. METHODS: Participants were asymptomatic subjects who underwent screening
      flexible sigmoidoscopy (FSG) within the Prostate, Lung, Colorectal, and Ovarian
      (PLCO) Cancer Screening Trial. Subjects underwent single-slice, computerized
      tomography scanning to measure VAT and serum fasting insulin, IGF-I, and IGFBP-3
      measurements. RESULTS: Four hundred fifty-eight subjects were enrolled, of which
      202 subjects had an adenoma, 70 of which were an advanced adenoma. IGF-I (P =
      .02), IGF-I/IGFBP-3 ratio (P = .003), and insulin (P = .02) were significantly
      increased in subjects with adenomas compared with controls. In an unadjusted
      logistic regression analysis using sex-specific quartile cut points, subjects in
      quartile 4 in comparison with quartile 1 of IGF-I (odds ratio [OR] = 1.7; [95%
      CI: 1.0-2.9], Ptrend = .03), IGF-I/IGFBP-3 ratio (OR = 1.9 [95% CI: 1.1-3.3],
      Ptrend = .01), and insulin (OR = 2.1 [95% CI: 1.2-3.6], Ptrend = .04) were at
      increased risk of adenoma. When limiting the case group to advanced adenomas, the
      effect was more pronounced: IGF-I (OR = 2.8 [95% CI: 1.3-6.2], Ptrend = .006),
      IGF-I/IGFBP-3 ratio (OR = 2.3, [95% CI: 1.0-5.2], Ptrend = .04), and insulin (OR
      = 2.3 [95% CI: 1.1-4.9], Ptrend = .14). Visceral adipose tissue was not
      associated with adenoma risk. CONCLUSIONS: Levels of IGF-I, ratio of IGF-I/IGFBP
      3, and insulin are associated with adenomas and even more so with advanced
      adenomas. These data support the hypothesis that insulin and IGF-I may contribute
      to the development and advancement of adenomatous polyps.

PMID- 16083704
TI  - Complementary stimulation of hepatobiliary transport and detoxification systems
      by rifampicin and ursodeoxycholic acid in humans.
AB  - BACKGROUND & AIMS: Rifampicin (RIFA) and ursodeoxycholic acid (UDCA) improve
      symptoms and biochemical markers of liver injury in cholestatic liver diseases by
      largely unknown mechanisms. We aimed to study the molecular mechanisms of action
      of these drugs in humans. METHODS: Thirty otherwise healthy gallstone patients
      scheduled for cholestectomy were randomized to RIFA (600 mg/day for 1 week) or
      UDCA (1 g/day for 3 weeks) or no medication before surgery. Routine biochemistry,
      lipids, and surrogate markers for P450 activity (4beta-hydroxy cholesterol, 4beta
      OH-C) and bile acid synthesis (7alpha-hydroxy-4-cholesten-3-one, C-4) were
      measured in serum. Bile acids were analyzed in serum, urine, and bile. A wedge
      liver biopsy specimen was taken to study expression of hepatobiliary ABC
      transporters as well as detoxification enzymes and regulatory transcription
      factors. RESULTS: RIFA enhanced bile acid detoxification as well as bilirubin
      conjugation and excretion as reflected by enhanced expression of CYP3A4, UGT1A1,
      and MRP2. These molecular effects were paralleled by decreased bilirubin and
      deoxycholic acid concentrations in serum and decreased lithocholic and
      deoxycholic acid concentrations in bile. UDCA on the other hand stimulated the
      expression of BSEP, MDR3, and MRP4. UDCA became the predominant bile acid after
      UDCA treatment and lowered the biliary cholesterol saturation index. CONCLUSIONS:
      RIFA enhances bile acid detoxification as well as bilirubin conjugation and
      export systems, whereas UDCA stimulates the expression of transporters for
      canalicular and basolateral bile acid export as well as the canalicular
      phospholipid flippase. These independent but complementary effects may justify a
      combination of both agents for the treatment of cholestatic liver diseases.

PMID- 16083705
TI  - Mortality and hospital utilization for hepatocellular carcinoma in the United
      States.
AB  - BACKGROUND & AIMS: The incidence of hepatocellular carcinoma (HCC) has been
      increasing in the United States. Although resource-intensive treatment modalities
      have been increasingly applied, these patients still have poor survival. We
      examined 2 nationally representative databases, the Multiple Cause of Death file
      and the Nationwide Inpatient Sample database, to examine trends in mortality and
      hospital service utilization related to HCC. METHODS: In both databases, a priori
      criteria were used to identify cases of HCC. All other available diagnostic
      fields were examined to characterize coexistent liver disease. Age-, sex-, and
      race-specific mortality from HCC was calculated, and temporal changes in
      mortality rates were evaluated using the multivariable Poisson model. Hospital
      service utilization was estimated based on length of stay, total hospitalization
      charges, and principal procedures. RESULTS: The age-, sex-, and race-specific
      mortality from HCC increased from 1.54 to 2.58 per 100,000 per year between 1980
      and 1998. Male sex, African and Asian race, and increasing age were also
      associated with higher mortality. The estimated total charge for HCC
      hospitalizations nationwide increased from 241 million US dollars in 1988 to 509
      million US dollars in 2000 after inflation adjustment. Commonly employed
      procedures in 2000 included angiography/embolization, resection, local ablative
      therapy, and liver transplantation. CONCLUSIONS: In the recent past, mortality
      and hospital service utilization related to HCC increased substantially. Closer
      epidemiologic surveillance to understand causation of HCC at the population level
      and to help implement primary and secondary prevention is urgently warranted.

PMID- 16083706
TI  - Survival after liver transplantation in patients with hepatic iron overload: the
      national hemochromatosis transplant registry.
AB  - BACKGROUND & AIMS: Previous uncontrolled studies have suggested that patients
      with hepatic iron overload have a poor outcome after liver transplantation. We
      examined the effect of HFE mutations on posttransplantation survival in patients
      with hepatic iron overload. METHODS: Two hundred sixty patients with end-stage
      liver disease and hepatic iron overload were enrolled from 12 liver
      transplantation centers. Hepatic iron concentration (HIC), hepatic iron index
      (HII), HFE mutation status, and survival after liver transplantation were
      recorded. RESULTS: HFE-associated hemochromatosis (HH) defined as homozygosity
      for the C282Y (n = 14, 7.2%) mutation or compound heterozygosity for the
      C282Y/H63D (n = 11, 5.6%) mutation was identified in 12.8% of patients. Survival
      postliver transplantation was significantly lower among patients with HH (1-, 3-,
      and 5-year survival rates of 64%, 48%, 34%, respectively) compared with simple
      heterozygotes (C282Y/wt or H63D/wt) or wild-type patients. Patients with HH had a
      hazard ratio for death of 2.6 (P = .002) after adjustment for age, United Network
      for Organ Sharing status, year of transplantation, and either elevated HII or
      HIC. Non-HH patients with hepatic iron overload also had significantly decreased
      survival when compared with the overall population undergoing liver
      transplantation (OR = 1.4, 95% CI: 1.15-1.61, P < .001). CONCLUSIONS: One- and 5
      year survivals after liver transplantation are significantly lower among patients
      with HFE-associated HH. Our data also suggest that hepatic iron overload may be
      associated with decreased survival after liver transplantation, even in patients
      without HH. Early diagnosis of hepatic iron overload using HFE gene testing and
      iron depletion prior to liver transplantation may improve posttransplantation
      survival, particularly among patients with HH.

PMID- 16083707
TI  - Probability of pancreatic cancer following diabetes: a population-based study.
AB  - BACKGROUND & AIMS: Although diabetes occurs frequently in pancreatic cancer, the
      value of new-onset diabetes as a marker of underlying pancreatic cancer is
      unknown. METHODS: We assembled a population-based cohort of 2122 Rochester,
      Minnesota, residents age > or =50 years who first met standardized criteria for
      diabetes between January 1, 1950, and December 31, 1994, and identified those who
      developed pancreatic cancer within 3 years of meeting criteria for diabetes. We
      compared observed rates of pancreatic cancer with expected rates based on the
      Iowa Surveillance Epidemiology and End Results registry. In a nested case control
      study, we compared body mass index (BMI) and smoking status in diabetes subjects
      with and without pancreatic cancer. RESULTS: Of 2122 diabetic subjects, 18
      (0.85%) were diagnosed with pancreatic cancer within 3 years of meeting criteria
      for diabetes; 10 of 18 (56%) were diagnosed <6 months after first meeting
      criteria for diabetes, and 3 were resected. The observed-to-expected ratio of
      pancreatic cancer in the cohort was 7.94 (95% CI, 4.70-12.55). Compared with
      subjects without pancreatic cancer, diabetic subjects with pancreatic cancer were
      more likely to have met diabetes criteria after age 69 (OR = 4.52, 95% CI, 1.61
      12.74) years but did not differ significantly with respect to BMI values (29.2 +/
      6.8 vs 26.5 +/- 5.0, respectively). A larger proportion of those who developed
      pancreatic cancer were ever smokers (92% vs 69%, respectively), but this did not
      reach statistical significance. CONCLUSIONS: Approximately 1% of diabetes
      subjects aged > or =50 years will be diagnosed with pancreatic cancer within 3
      years of first meeting criteria for diabetes. The usefulness of new-onset
      diabetes as marker of early pancreatic cancer needs further evaluation.

PMID- 16083708
TI  - Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish
      registry over a 10-year period.
AB  - BACKGROUND & AIMS: Progress in the understanding of susceptibility factors to
      drug-induced liver injury (DILI) and outcome predictability are hampered by the
      lack of systematic programs to detect bona fide cases. METHODS: A cooperative
      network was created in 1994 in Spain to identify all suspicions of DILI following
      a prospective structured report form. The liver damage was characterized
      according to hepatocellular, cholestatic, and mixed laboratory criteria and to
      histologic criteria when available. Further evaluation of causality assessment
      was centrally performed. RESULTS: Since April 1994 to August 2004, 461 out of 570
      submitted cases, involving 505 drugs, were deemed to be related to DILI. The
      antiinfective group of drugs was the more frequently incriminated, amoxicillin
      clavulanate accounting for the 12.8% of the whole series. The hepatocellular
      pattern of damage was the most common (58%), was inversely correlated with age (P
      < .0001), and had the worst outcome (Cox regression, P < .034). Indeed, the
      incidence of liver transplantation and death in this group was 11.7% if patients
      had jaundice at presentation, whereas the corresponding figure was 3.8% in
      nonjaundiced patients (P < .04). Factors associated with the development of
      fulminant hepatic failure were female sex (OR = 25; 95% CI: 4.1-151; P < .0001),
      hepatocellular damage (OR = 7.9; 95% CI: 1.6-37; P < .009), and higher baseline
      plasma bilirubin value (OR = 1.15; 95% CI: 1.09-1.22; P < .0001). CONCLUSIONS:
      Patients with drug-induced hepatocellular jaundice have 11.7% chance of
      progressing to death or transplantation. Amoxicillin-clavulanate stands out as
      the most common drug related to DILI.

PMID- 16083709
TI  - Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with
      genotype 2 or 3 chronic hepatitis C.
AB  - BACKGROUND & AIMS: Standard therapy of patients with chronic hepatitis C virus
      (HCV) infected with HCV genotype-2 or -3 is the combination of pegylated
      interferon-alpha and ribavirin for 24 weeks. Whether shorter treatment durations
      are possible for these patients without compromising sustained virologic response
      rates is unknown. METHODS: Patients chronically infected with HCV-2 (n = 39), HCV
      2/3 (n = 1), or HCV-3 (n = 113) were treated with peginterferon-alpha-2a (180
      microg/wk) plus ribavirin 800-1200 mg/day. HCV RNA was quantitatively assessed
      after 4 weeks. Patients with a rapid virologic response (HCV RNA below 600 IU/mL)
      were randomized for a total treatment duration of 16 (group A) or 24 weeks (group
      B). All patients with HCV RNA > or =600 IU/mL at week 4 (group C) were treated
      for 24 weeks. End-of-treatment and sustained virologic response were assessed by
      qualitative RT-PCR (sensitivity 50 IU/mL). RESULTS: Only 11 of 153 patients (7%)
      were allocated to group C. End-of-treatment and sustained virologic response
      rates were 94% and 82%, (group A), 85% and 80% (group B), and 73% and 36% (group
      C), respectively. In patients infected with genotype HCV-3 and high viral load
      (>800,000 IU/mL), a significant lower sustained virologic response rate was found
      than in patients infected with HCV-3 and a viral load lower or equal to 800,000
      IU/mL (59% vs 85%, respectively; P = .003). CONCLUSIONS: In HCV-2 and -3 (low
      viral load)-infected patients who have a rapid virologic response, treatment for
      16 weeks with peginterferon-alpha-2a and ribavirin is sufficient. In patients
      infected by HCV-3 (high viral load), longer treatment may be necessary.

PMID- 16083710
TI  - A 1-year trial of telbivudine, lamivudine, and the combination in patients with
      hepatitis B e antigen-positive chronic hepatitis B.
AB  - BACKGROUND & AIMS: A previous 4-week trial of telbivudine in patients with
      chronic hepatitis B indicated marked antiviral effects with good tolerability,
      leading to the present 1-year phase 2b trial. METHODS: This randomized, double
      blind, multicenter trial evaluated the efficacy and safety of telbivudine 400 or
      600 mg/day and telbivudine 400 or 600 mg/day plus lamivudine 100 mg/day (Comb400
      and Comb600) compared with lamivudine 100 mg/day in hepatitis B e antigen (HBeAg)
      positive adults with compensated chronic hepatitis B. RESULTS: A total of 104
      patients were randomized 1:1:1:1:1 among the 5 groups. Median reductions in serum
      hepatitis B virus (HBV) DNA levels at week 52 (log(10) copies/mL) were as
      follows: lamivudine, 4.66; telbivudine 400 mg, 6.43; telbivudine 600 mg, 6.09;
      Comb400, 6.40; and Comb600, 6.05. At week 52, telbivudine monotherapy showed a
      significantly greater mean reduction in HBV DNA levels (6.01 vs 4.57 log(10)
      copies/mL; P < .05), clearance of polymerase chain reaction-detectable HBV DNA
      (61% vs 32%; P < .05), and normalization of alanine aminotransferase levels (86%
      vs 63%; P < .05) compared with lamivudine monotherapy, with proportionally
      greater HBeAg seroconversion (31% vs 22%) and less viral breakthrough (4.5% vs
      15.8%) (P = NS for both). Combination treatment was not better than telbivudine
      alone. All treatments were well tolerated. In exploratory scientific analyses,
      clinical efficacy at 1 year appeared related to reduction in HBV DNA levels in
      the first 6 months of treatment. CONCLUSIONS: Patients with chronic hepatitis B
      treated with telbivudine exhibited significantly greater virologic and
      biochemical responses compared with lamivudine. Results with the combination
      regimens were similar to those obtained with telbivudine alone. These data
      support the ongoing phase 3 evaluation of telbivudine for treatment of patients
      with chronic hepatitis B.

PMID- 16083711
TI  - Functional significance and clinical phenotype of nontruncating mismatch repair
      variants of MLH1.
AB  - BACKGROUND & AIMS: Germline mutations in mismatch repair genes are associated
      with hereditary nonpolyposis colorectal cancer. A significant proportion of
      mutations are nontruncating and associated with a variability of clinical
      phenotype and microsatellite instability and with occasional presence of residual
      protein in tumor tissue that suggests impaired functional activity but not total
      lack of mismatch repair. To address pathogenic significance and mechanism of
      pathogenicity, we studied the functionality of 31 nontruncating MLH1 mutations
      found in clinically characterized colorectal cancer families and 3 other
      variations listed in a mutation database. METHODS: Mutations constructed by site
      directed mutagenesis were studied for protein expression/stability, subcellular
      localization, protein-protein interaction, and repair efficiency. The genetic and
      biochemical data were correlated with clinical data. Finally, comparative
      sequence analysis was performed to assess the value of sequence homology as a
      tool for predicting functional results. RESULTS: Altogether, 22 mutations were
      pathogenic in more than one assay, 2 variants were impaired in one assay, and 10
      variants acted like wild-type protein. Twenty of 34 mutations affected the
      quantity of MLH1 protein, whereas only 15 mainly amino-terminal mutations were
      defective in an in vitro repair assay. Comparative sequence analysis correctly
      predicted functional studies for 82% of variants. CONCLUSIONS: Pathogenic
      nontruncating alterations in MLH1 may interfere with different biochemical
      mechanisms but generally more than one. The severe biochemical defects are
      mirrored by phenotypic characteristics such as early age at onset and high
      microsatellite instability, whereas variants with no or mild defects in
      functionality are associated with variable clinical phenotypes.

PMID- 16083712
TI  - Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that
      affects epithelial tight junctions, apoptosis, and cell restitution.
AB  - BACKGROUND & AIMS: Ulcerative colitis (UC) is characterized by a Th2 immune
      response with inflammation and epithelial barrier dysfunction. So far, Th2
      cytokines have not been shown to directly influence epithelial barrier function.
      METHODS: Lamina propria mononuclear cells (LPMCs) were stimulated and interleukin
      (IL)-13 was measured by enzyme-linked immunosorbent assay. Functional IL-13 and
      IL-4 effects were studied on HT-29/B6 colonic epithelial cells in Ussing chambers
      and by conductance scanning. Apoptosis was detected by terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling assays. IL-13/IL
      4 receptors were analyzed by reverse-transcription polymerase chain reaction and
      immunofluorescence. Western blotting combined with immunofluorescence was used to
      detect tight junction proteins. Furthermore, restitution velocity was measured.
      Finally, mucosal biopsy specimens from patients with UC were compared with
      cultured cells for these features. RESULTS: LPMCs from patients with UC produced
      large amounts of IL-13 (985 +/- 73 pg/mL), much more than from controls or
      patients with Crohn's disease. IL-13Ralpha1 and IL-4Ralpha receptors were present
      in HT-29/B6 cells and colonic epithelial cells of control patients and patients
      with UC. IL-13 had a dose-dependent effect on transepithelial resistance of HT
      29/B6 monolayers (reduction to 60% +/- 4%), whereas IL-4 had no effect. This was
      due to an increased number of apoptotic cells (5.6-fold +/- 0.9-fold) and an
      increased expression of the pore-forming tight junction protein claudin-2 to 295%
      +/- 37%, both of which contributed equally. Finally, epithelial restitution
      velocity decreased from 15.1 +/- 0.6 to 10.6 +/- 0.5 microm/h after treatment
      with IL-13. Parallel changes were observed in human samples, with an increase in
      claudin-2 expression to 956% +/- 252%. CONCLUSIONS: IL-13 was identified as an
      important effector cytokine in UC that impairs epithelial barrier function by
      affecting epithelial apoptosis, tight junctions, and restitution velocity.

PMID- 16083713
TI  - Identification of functional genetic variants in cyclooxygenase-2 and their
      association with risk of esophageal cancer.
AB  - BACKGROUND & AIMS: Overexpression of cyclooxygenase-2 (COX-2) is implicated in
      many steps of cancer development. Single nucleotide polymorphisms (SNPs) in the
      COX-2 promoter might contribute to differential COX-2 expression and subsequent
      interindividual variability in susceptibility to cancer. This study sought to
      identify functional SNPs in the COX-2 promoter and evaluated their effects on the
      risk of developing esophageal squamous cell carcinoma (ESCC). METHODS: Thirty
      individual DNA samples were sequenced to search for SNPs, and the function of the
      SNPs was examined by a set of biochemical assays. Genotypes and haplotypes were
      analyzed in 1026 patients and 1270 controls, and odds ratios and 95% confidence
      intervals (CIs) were estimated by logistic regression. RESULTS: Three SNPs, 
      1290A-->G, -1195G-->A, and -765G-->C, were identified; the frequencies of variant
      alleles were 0.04, 0.51, and 0.02, respectively. The -1195G-->A change creates a
      c-MYB binding site and displays a higher promoter activity. The -1195A-containing
      haplotypes had significantly increased luciferase expression and COX-2 messenger
      RNA levels in esophageal tissues compared with the -1195G-containing
      counterparts. A case-control analysis showed a 1.72-fold (95% CI, 1.35-2.20) and
      2.24-fold (95% CI, 1.59-3.16) excess risk of developing ESCC for the -1195AA or 
      765CC genotype carriers compared with noncarriers. A greater risk of developing
      ESCC was observed for A(-1195)-C(-765)-containing haplotypes compared with G(
      1195)-G(-765)-containing haplotypes, suggesting an interaction between the -1195G
      ->A and -765G-->C polymorphisms in the context of haplotype. CONCLUSIONS: These
      findings indicate that genetic variants in COX-2 may play a role in mediating
      susceptibility to esophageal cancer.

PMID- 16083714
TI  - Oncogenic potential of MEK1 in rat intestinal epithelial cells is mediated via
      cyclooxygenase-2.
AB  - BACKGROUND & AIMS: The mitogen-activated protein kinase/extracellular signal
      regulated protein kinase kinase (MEK) pathway plays an important role in the
      regulation of cell growth and differentiation. Constitutively active components
      of the MEK signaling cascade can induce oncogenic transformation in many cell
      systems. Downstream MEK signaling also plays an important role in the regulation
      of cyclooxygenase-2 (COX-2), which is known to be involved in colorectal cancer.
      Therefore, we determined the role of COX-2 on the oncogenic potential of MEK1 in
      nontransformed rat intestinal epithelial cells. METHODS: Constitutively active
      MEK1 (CA-MEK) mutant transfected rat intestinal epithelial cells were established
      and tested for their ability to grow in soft agar and form tumors in vivo. The
      effect of CA-MEK on sodium butyrate (NaB)-induced apoptosis was evaluated by the
      Annexin V assay. The transcriptional activity and posttranscriptional stability
      of the COX-2 gene was determined by transient transfection with COX-2 reporter
      variants and by Northern analysis. To address the role of COX-2 in tumor growth
      in vivo, xenografted mice were treated with celecoxib (100 mg/kg) or vehicle.
      RESULTS: CA-MEK transfected RIE-1 and IEC-6 cells formed colonies in soft agar
      and tumors in nude mice. These cells showed resistance to NaB-induced apoptosis
      and cell cycle arrest. MEK activation led to increased expression of COX-2, Bcl
      X(L), Mcl-1, and phosphorylated Bad and decreased expression of Bak. Along with
      elevated COX-2 levels, PGI(2) and PGE(2) levels were also increased.
      Pharmacologic inhibition of COX-2 inhibited MEK-induced tumor growth in vivo
      through enhanced apoptosis. CONCLUSIONS: COX-2 and its bioactive lipid products
      may play an important role in MEK-induced transformation.

PMID- 16083715
TI  - Epidermal growth factor partially restores colonic ion transport responses in
      mouse models of chronic colitis.
AB  - BACKGROUND & AIMS: Epidermal growth factor receptor (EGFR) activation, which
      plays an important role in regulating intestinal ion transport, can alleviate
      clinical symptoms such as diarrhea in patients with ulcerative colitis and
      promote mucosal restitution in animal models of colitis. Here, we investigate
      whether EGFR can regulate colonic ion transport in the setting of colitis.
      METHODS: Distal colon from control mice and mice with colitis was retained for
      immunohistochemistry or mounted in Ussing chambers. Ion transport responses
      across the tissues to the calcium agonist carbachol and the adenosine 3',5'
      cyclic monophosphate agonist forskolin were measured with or without epidermal
      growth factor (EGF) pretreatment. RESULTS: EGF pretreatment of normal colonic
      mucosa inhibited ion transport responses to carbachol and forskolin but
      potentiated the reduced ion transport responses seen in dextran sulfate sodium
      (DSS)-treated and mdr1a knockout mouse colon. Ion substitution studies and the
      sodium transport inhibitor amiloride showed that sodium movement primarily
      accounted for the potentiating effect of EGF in DSS-treated tissues, despite
      decreased sodium channel expression. EGF potentiation of transport responses in
      DSS-treated colon was completely blocked by the cytoskeletal disruptor
      cytochalasin D and the phosphatidylinositol 3-kinase inhibitor wortmannin,
      whereas the novel and conventional protein kinase C isoform inhibitor Go6850 and
      the extracellular signal-regulated kinase inhibitor PD98059 partially reduced EGF
      effects. EGFR epithelial distribution and transforming growth factor alpha
      expression were also altered in DSS-treated tissues. CONCLUSIONS: Chronic
      inflammation uncovers a potentiating effect of EGFR activation on epithelial
      electrogenic sodium absorption that would be expected to ameliorate diarrheal
      symptoms associated with colitis.

PMID- 16083716
TI  - HB-EGF enhances restitution after intestinal ischemia/reperfusion via PI3K/Akt
      and MEK/ERK1/2 activation.
AB  - BACKGROUND & AIMS: Early recovery of intestinal function after injury occurs by
      restitution, a complex process with a poorly understood molecular basis. Heparin
      binding epidermal growth factor-like growth factor (HB-EGF) is a potent
      chemotactic factor that is induced during ischemia/reperfusion in vivo and
      intestinal wounding in vitro. The role of HB-EGF in intestinal restitution and
      the underlying intracellular signaling pathways involved were investigated.
      METHODS: Adult rats were subjected to intestinal ischemia, with histologic and
      biochemical damage assessed during the first 3 hours of reperfusion. The effect
      of recombinant HB-EGF (rHB-EGF) on structural and functional recovery of the
      intestine by restitution was evaluated in vivo. Scrape wounding of intestinal
      epithelial cell monolayers was used to elucidate the mechanisms of intrinsic and
      rHB-EGF-induced restitution. RESULTS: Early structural recovery occurred within 3
      hours of reperfusion and was attributed to restitution rather than proliferation.
      HB-EGF treatment significantly improved structural recovery and accelerated
      functional recovery of the gut barrier. In vivo restitution was preceded by
      activation of Akt and extracellular signal-regulated kinase (ERK) 1/2, which were
      accelerated and enhanced by HB-EGF treatment. Blocking of ErbB-1,
      phosphatidylinositol 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase/ERK
      kinase (MEK)/ERK activity resulted in significant reduction in intrinsic and HB
      EGF-induced restitution in vitro. Endogenous HB-EGF was shown to play an
      essential role in wound-induced ErbB-1 and ERK1/2 activation and in intrinsic
      restitution. CONCLUSIONS: Endogenous HB-EGF, ErbB-1, PI3K/Akt, and MEK/ERK are
      involved in intrinsic restitution. rHB-EGF enhances restitution in vivo and in
      vitro in a PI3K/Akt- and MEK/ERK1/2-dependent fashion.

PMID- 16083717
TI  - Expression pattern of Wnt signaling components in the adult intestine.
AB  - BACKGROUND & AIMS: In the intestine, the canonical Wnt signaling cascade plays a
      crucial role in driving the proliferation of epithelial cells. Furthermore,
      aberrant activation of Wnt signaling is strongly associated with the development
      of colorectal cancer. Despite this evidence, little is known about the precise
      identity and localization of Wnts and their downstream effectors in the adult
      intestine. To address this issue, we examined the expression pattern of all Wnts,
      Frizzleds (Fzs), low-density lipoprotein receptor-related proteins, Wnt
      antagonists, and T-cell factors in the murine small intestine and colon and
      adenomas. METHODS: Embryonic, postnatal, and adult intestinal samples were
      subjected to in situ hybridization by using specific RNA probes for the various
      genes tested. RESULTS: Our analysis showed high expression of several signaling
      components (including Wnt-3, Wnt-6, Wnt-9b, Frizzled 4, Frizzled 6, Frizzled 7,
      low-density lipoprotein receptor-related protein 5, and secreted Frizzled-related
      protein 5) in crypt epithelial cells. We also detected Wnt-2b, Wnt-4, Wnt-5a, Wnt
      5b, Frizzled 4, and Frizzled 6 in differentiated epithelial and mesenchymal cells
      of the small intestine and colon. Finally, several factors (Frizzled 4, T-cell
      factor 1, lymphoid enhancer factor, Dickkopf 2, Dickkopf 3, and Wnt-interacting
      factor) displayed differential expression in normal vs neoplastic tissue.
      CONCLUSIONS: Our study predicts a much broader role for Wnt signaling in gut
      development and homeostasis than was previously anticipated from available
      genetic studies and identifies novel factors likely involved in promoting
      canonical and noncanonical Wnt signals in the intestine.

PMID- 16083718
TI  - Tumor necrosis factor-alpha mediates pancreatitis responses in acinar cells via
      protein kinase C and proline-rich tyrosine kinase 2.
AB  - BACKGROUND & AIMS: Although tumor necrosis factor alpha is implicated as an
      important mediator of the inflammatory response in acute pancreatitis, its role
      in other pathologic features of the disease remains unknown. We investigated the
      role for tumor necrosis factor alpha in cytoskeletal responses and the underlying
      signaling mechanisms in pancreatic acinar cells. METHODS: In isolated rat
      pancreatic acini and AR42J cells, we determined the effect of tumor necrosis
      factor alpha on the actin cytoskeleton by rhodamine-phalloidin. Using
      pharmacological and molecular approaches, we assessed the involvement of protein
      kinase C, Src kinases, and proline-rich tyrosine kinase 2 in the process. We also
      studied the involvement of these signaling pathways in tumor necrosis factor
      alpha-induced nuclear factor-kappaB activation and apoptosis. RESULTS: Tumor
      necrosis factor-alpha increased the tyrosine phosphorylation of proline-rich
      tyrosine kinase 2 in acinar cells. The broad-spectrum protein kinase C inhibitor
      and the Src kinase inhibitor both inhibited tumor necrosis factor-alpha-induced
      proline-rich tyrosine kinase 2 phosphorylation, but at different tyrosine
      residues. Using protein kinase C isoform-specific inhibitors and the antisense
      approach, we showed that protein kinase C delta and mediate proline-rich tyrosine
      kinase 2 tyrosine phosphorylation. Tumor necrosis factor-alpha caused
      disorganization of the actin cytoskeleton by a mechanism dependent on protein
      kinase C, Src kinases, and proline-rich tyrosine kinase 2. Inhibition of protein
      kinase C, but not Src kinases, decreased tumor necrosis factor-alpha-induced
      apoptosis. Furthermore, with antisense transfections, we showed that protein
      kinase C delta and , but not proline-rich tyrosine kinase 2, mediate tumor
      necrosis factor alpha-induced nuclear factor-kappaB activation. CONCLUSIONS:
      Tumor necrosis factor-alpha activates proline-rich tyrosine kinase 2 to cause
      cytoskeletal disorganization and nuclear factor-kappaB to cause inflammatory
      response, and it triggers cell death signaling through divergent mechanisms
      mediated by protein kinase C. The results provide insights into the mechanisms in
      pancreatic acinar cells that link tumor necrosis factor alpha to critical
      processes in acute pancreatitis.

PMID- 16083719
TI  - Free radical-dependent dysfunction of small-for-size rat liver grafts: prevention
      by plant polyphenols.
AB  - BACKGROUND & AIMS: The mechanisms by which small-for-size liver grafts decrease
      survival remain unclear. This study investigated the role of free radicals in
      injury to small-for-size grafts. METHODS: Rat liver explants were reduced in size
      ex vivo and transplanted into recipients of the same or greater body weight,
      resulting in a graft weight and standard liver weight of approximately 50% and
      25%, respectively. A polyphenol extract from Camellia sinenesis (20 microg/mL) or
      an equivalent concentration of epicatechin was added to the storage solution and
      the lactated Ringer poststorage rinse solution. RESULTS: Serum alanine
      aminotransferase release increased from approximately 60 U/L before implantation
      to 750, 1410, and 2520 U/L after full-size, half-size, and quarter-size
      transplantation, respectively. Total bilirubin increased slightly after
      transplantation of full-size and half-size grafts but increased 104-fold in
      quarter-size grafts. In quarter-size grafts, histological changes included
      necrosis, leukocyte infiltration, and eosinophilic inclusion body formation.
      Polyphenol treatment ameliorated these effects by > or =67%. Survival was 30%
      after transplantation of small-for-size grafts. After polyphenol treatment,
      survival increased to 70%. Free radicals in bile assessed by spin trapping and 4
      hydroxynonenal adducts measured by immunohistochemistry were also greater in
      reduced-size grafts, an effect ameliorated by polyphenols. Epicatechin, a major
      polyphenol from Camellia sinenesis, also improved graft function and decreased
      enzyme release, histopathologic changes, and free radical formation. CONCLUSIONS:
      Increased formation of free radicals occurs after transplantation of reduced-size
      livers, which contributes to graft dysfunction and failure. Plant polyphenols
      decrease liver graft injury and increase survival of small-for-size liver grafts,
      most likely by scavenging free radicals.

PMID- 16083720
TI  - A proinflammatory, antiapoptotic phenotype underlies the susceptibility to acute
      pancreatitis in cystic fibrosis transmembrane regulator (-/-) mice.
AB  - BACKGROUND & AIMS: Cystic fibrosis transmembrane regulator (CFTR) gene mutations
      are associated with pancreatic insufficiency and pancreatitis. Chronic
      pancreatitis, including cystic fibrosis-related disease, may exist as a continuum
      between acute and chronic disease and may manifest as recurrent pain. We
      hypothesized that cftr(m1UNC) (-/-) mice, which have no evidence of chronic
      pancreatitis, are susceptible to developing acute pancreatitis. METHODS: We used
      a cerulein hyperstimulation model of acute pancreatitis and measured histological
      changes, tissue edema, neutrophil infiltration, inflammatory mediators' mRNA
      expression, apoptosis markers, and pancreatic trypsin and serum lipase
      activities. Additionally, we quantitated in vivo pancreatic secretion and
      pancreatic digestive enzymes. RESULTS: Multiple proinflammatory cytokine genes
      were constitutively overexpressed in cftr (-/-) pancreas compared with wild-type
      mice. During acute pancreatitis, cftr (-/-) mice developed more severe acute
      pancreatitis than wild-type, as indicated by greater pancreatic edema, neutrophil
      infiltration, mRNA expression of multiple inflammatory mediators, and less
      apoptotic cell death. In contrast to wild-type mice, cftr (-/-) mice had blunted
      increases in pancreatic trypsin and serum lipase activities, but similar
      percentages of pancreatic trypsinogen activation. Finally, cftr (-/-) mice had
      less in vivo pancreatic secretion in response to cholecystokinin octapeptide and
      reduced pancreatic digestive enzyme protein and mRNA levels, thus suggesting mild
      pancreatic insufficiency. CONCLUSIONS: A baseline proinflammatory state and an
      antiapoptotic phenotype may sensitize cftr (-/-) mice to developing more severe
      acute pancreatitis with an exuberant pancreatic inflammatory response. Cftr (-/-)
      mice have mild pancreatic insufficiency, which partially explains the blunted
      increase of pancreatic and serum digestive enzymes during acute pancreatitis.
      These findings may explain the susceptibility to acute pancreatitis in persons
      with classic and nonclassic cystic fibrosis.

PMID- 16083722
TI  - Autophagic cell death of pancreatic acinar cells in serine protease inhibitor
      Kazal type 3-deficient mice.
AB  - BACKGROUND & AIMS: Serine protease inhibitor Kazal type 1 (SPINK1), which is
      structurally similar to epidermal growth factor, is thought to inhibit trypsin
      activity and to prevent pancreatitis. Point mutations in the SPINK1 gene seem to
      predispose humans to pancreatitis; however, the clinical significance of SPINK1
      mutations remains controversial. This study aimed to elucidate the role of
      SPINK1. METHODS: We generated Spink3-deficient (Spink3(-/-)) mice by gene
      targeting in mouse embryonic stem cells. Embryonic and neonatal pancreases were
      analyzed morphologically and molecularly. Specific probes were used to show the
      typical autophagy that occurs during acinar cell death. RESULTS: In Spink3(-/-)
      mice, the pancreas developed normally up to 15.5 days after coitus. However,
      autophagic degeneration of acinar cells, but not ductal or islet cells, started
      from day 16.5 after coitus. Rapid onset of cell death occurred in the pancreas
      and duodenum within a few days after birth and resulted in death by 14.5 days
      after birth. There was limited inflammatory cell infiltration and no sign of
      apoptosis. At 7.5 days after birth, residual ductlike cells in the tubular
      complexes strongly expressed pancreatic duodenal homeodomain-containing protein
      1, a marker of pancreatic stem cells, without any sign of acinar cell
      regeneration. CONCLUSIONS: The progressive disappearance of acinar cells in
      Spink3(-/-) mice was due to autophagic cell death and impaired regeneration.
      Thus, Spink3 has essential roles in the maintenance of integrity and regeneration
      of acinar cells.

PMID- 16083721
TI  - Cholangiocyte endothelin 1 and transforming growth factor beta1 production in rat
      experimental hepatopulmonary syndrome.
AB  - BACKGROUND & AIMS: Hepatic production and release of endothelin 1 plays a central
      role in experimental hepatopulmonary syndrome after common bile duct ligation by
      stimulating pulmonary endothelial nitric oxide production. In thioacetamide
      induced nonbiliary cirrhosis, hepatic endothelin 1 production and release do not
      occur, and hepatopulmonary syndrome does not develop. However, the source and
      regulation of hepatic endothelin 1 after common bile duct ligation are not fully
      characterized. We evaluated the sources of hepatic endothelin 1 production after
      common bile duct ligation in relation to thioacetamide cirrhosis and assessed
      whether transforming growth factor beta1 regulates endothelin 1 production.
      METHODS: Hepatopulmonary syndrome and hepatic and plasma endothelin 1 levels were
      evaluated after common bile duct ligation or thioacetamide administration.
      Cellular sources of endothelin 1 were assessed by immunohistochemistry and laser
      capture microdissection of cholangiocytes. Transforming growth factor beta1
      expression and signaling were assessed by using immunohistochemistry and Western
      blotting and by evaluating normal rat cholangiocytes. RESULTS: Hepatic and plasma
      endothelin 1 levels increased and hepatopulmonary syndrome developed only after
      common bile duct ligation. Hepatic endothelin 1 and transforming growth factor
      beta1 levels increased over a similar time frame, and cholangiocytes were a major
      source of each peptide. Transforming growth factor beta1 signaling in
      cholangiocytes in vivo was evident by increased phosphorylation and nuclear
      localization of Smad2, and hepatic endothelin 1 levels correlated directly with
      liver transforming growth factor beta1 and phosphorylated Smad2 levels.
      Transforming growth factor beta1 also stimulated endothelin 1 promoter activity,
      expression, and production in normal rat cholangiocytes. CONCLUSIONS:
      Cholangiocytes are a major source of hepatic endothelin 1 production during the
      development of hepatopulmonary syndrome after common bile duct ligation, but not
      in thioacetamide-induced cirrhosis. Transforming growth factor beta1 stimulates
      cholangiocyte endothelin 1 expression and production. Cholangiocyte-derived
      endothelin 1 may be an important endocrine mediator of experimental
      hepatopulmonary syndrome.

PMID- 16083723
TI  - Life-threatening chronic enteritis due to colonization of the small bowel with
      Stenotrophomonas maltophilia.
AB  - Chronic diarrheal illness and malabsorption are challenging diagnostic and
      clinical problems. The identification of the causative pathogens that are
      involved in gastrointestinal infections is often difficult. It took 85 years
      after the first description of a case of intestinal lipodystrophy by Georg
      Whipple in 1907 until the causative bacterium was characterized by using
      molecular genetics techniques. We here report the complicated clinical course of
      a young patient with chronic diarrhea accompanied by severe, life-threatening
      malabsorption with extensive weight loss. Histology and glucose hydrogen breath
      test were suggestive of a bacterial overgrowth syndrome in the small bowel, but
      standard culture-based techniques and serology failed to identify the causative
      bacteria. Thus, bacterial ribosomal DNA (16S ribosomal DNA) was extracted from
      duodenal biopsy samples and analyzed by community fingerprinting and species
      specific polymerase chain reaction. Stenotrophomonas maltophilia was identified
      as the cause of chronic infectious enteritis. Only specific long-term antibiotic
      treatment with co-trimoxazole had a durable clinical effect and led to
      normalization of 16S ribosomal DNA profiles. This case shows the role of rare and
      uncommon bacteria in refractory and chronic human gastrointestinal infections.
      Genomic techniques, including 16S-based single-strand conformation polymorphism
      analysis, will play an increasing role in the diagnosis of chronic infections
      with facultatively pathogenic bacteria or in the clinical analysis of complex
      bacterial communities such as the intestinal bacterial microflora. Future
      enhancements in detection techniques will show that chronic bacterial infections
      are more frequent as a cause of gastrointestinal malfunction than commonly
      thought.

PMID- 16083724
TI  - Analysis of the biliary transcriptome in experimental biliary atresia.
AB  - BACKGROUND & AIMS: Discovery of the pathogenic mechanisms of biliary atresia has
      been limited by the inability to study extrahepatic biliary tissues from patients
      at early phases of disease. Here, we used a rotavirus-induced model of biliary
      atresia to investigate the entire biliary transcriptome for molecular networks
      activated at the onset and different phases of progression to duct obstruction.
      METHODS: We injected Balb/c mice with saline or rotavirus intraperitoneally
      within 24 hours of birth, microdissected the gallbladder and extrahepatic bile
      ducts en bloc 3, 7, and 14 days later, generated biotinylated RNA pools, and
      hybridized them against microarrays containing 45,101 gene products. RESULTS:
      Data filtering, cluster analysis, and functional assignment of the gene
      expression platform revealed 2 unique patterns of expression. The first was an
      overarching expression of genes regulating immunity, enzymes, and structural
      proteins at all phases of atresia. Within this pattern, the sequential expression
      of the interferon inducers Irf7 and Irf9 at the onset of injury, and interferon
      gamma and interferon-gamma-activated genes (Stat1, Igtp, Cxcl9, Cxcl10) at the
      time of duct obstruction, pointed to a prominent proinflammatory circuit. The
      second was the time-restricted expression of genes regulating biological networks
      previously unrecognized in biliary atresia, such as the complement components
      C3ar-1 and C1q-alpha/beta. CONCLUSIONS: The coordinate expression of functionally
      related genes in the biliary transcriptome underscores a predominant
      proinflammatory footprint and provides a basis for identification of gene groups
      that may play regulatory roles in the pathogenesis of duct injury and obstruction
      in experimental biliary atresia.

PMID- 16083725
TI  - New insights into the genetic regulation of intestinal cholesterol absorption.
AB  - The small intestine is a unique organ providing dietary and reabsorbed biliary
      cholesterol to the body. However, the molecular mechanisms whereby cholesterol is
      absorbed have not yet been fully understood. Recent research suggests that the
      newly identified Niemann-Pick C1-like 1 protein (NPC1L1) is expressed at the
      apical surface of enterocytes and plays a critical role in the absorption of
      intestinal cholesterol. Furthermore, adenosine triphosphate (ATP)-binding
      cassette (ABC) transporters ABCG5 and ABCG8 represent apical sterol export pumps
      that promote active efflux of cholesterol and plant sterols from enterocytes back
      into the intestinal lumen for excretion. This provides an explanation why
      cholesterol absorption is a selective process, with plant sterols and other
      noncholesterol sterols being absorbed poorly or not at all. These findings
      strongly support the concept that cholesterol absorption is a multistep process,
      which is regulated by multiple genes at the enterocyte level. The absorption
      efficiency of cholesterol is most likely determined by the net effect between
      influx and efflux of intraluminal cholesterol molecules across the brush border
      of the enterocyte. Combination therapy using a novel, specific, and potent
      cholesterol absorption (NPC1L1) inhibitor (ezetimibe) and HMG-CoA reductase
      inhibitors (statins) offers an efficacious new approach to the prevention and
      treatment of hypercholesterolemia.

PMID- 16083726
TI  - Nuclear receptor ligands: rational and effective therapy for chronic cholestatic
      liver disease?

PMID- 16083727
TI  - It is time to get serious about diagnosing Lynch syndrome (hereditary
      nonpolyposis colorectal cancer with defective DNA mismatch repair) in the general
      population.

PMID- 16083728
TI  - Colon Cancer Screening Guidelines 2005: the fecal occult blood test option has
      become a better FIT.

PMID- 16083729
TI  - Reducing the risk that patients get it wrong.

PMID- 16083730
TI  - Lynch syndrome: form, function, proteins, and basketball.

PMID- 16083731
TI  - Proton pump inhibitors in acute peptic ulcer bleeding.

PMID- 16083732
TI  - Screening with a fecal multitarget DNA test.

PMID- 16083734
TI  - Fecal flora in irritable bowel syndrome: characterization using molecular
      methods.

PMID- 16083735
TI  - What are Helicobacter doing in the hepatobiliary system?

PMID- 16083736
TI  - A new platform for gene discovery in pancreatic cancer.

PMID- 16083737
TI  - "Sham" on the academic ivory tower.

PMID- 16083738
TI  - Trichuris suis therapy for ulcerative colitis: nonresponsive patients may need
      anti-helminth therapy.

PMID- 16083740
TI  - Liver transplantation is a time-dependent prognostic predictor in cirrhotic
      patients with esophageal varices.

PMID- 16083743
TI  - Inflammation's role in rectal cancer following prostate radiotherapy, and
      emerging evidence for a protective role for balsalazide.

PMID- 16083745
TI  - Failure to define what constitutes a patient responder is a problem in the
      interpretation of the probiotic clinical trial evaluating the use of
      Bifidobacterium in irritable bowel syndrome.

PMID- 16083746
TI  - Prostate radiotherapy is associated with second cancers in many organs, not just
      the colorectum.

PMID- 16083748
TI  - Growth hormone, burn injury, and intestinal homeostasis.

PMID- 16083749
TI  - Protective effect of resveratrol against oxidative stress in cholestasis.
AB  - BACKGROUND: We investigated the protective role of resveratrol in rat liver
      injuries induced by chronic biliary obstruction. MATERIALS AND METHODS: Secondary
      biliary cirrhosis was induced by bile duct ligation for 28 days. Swiss albino
      rats were divided into the three following groups: group 1: sham (n = 7); group
      2: bile duct ligation (n = 7); group 3: bile duct ligation plus resveratrol (n =
      7). Bile duct ligation plus resveratrol group received 10 mg/kg dose of
      resveratrol intraperitoneally daily for 28 days. Liver damage and cholestasis
      were determined by the biochemical and the pathologic examination. RESULTS: The
      present data showed a decrease in both plasma bilirubin levels and aspartate
      aminotransferase and alanine aminotransferase levels in the resveratrol-treated
      rats, when compared with bile duct ligation group (P < 0.05). In the resveratrol
      treated rats, tissue levels of malondialdehyde and nitric oxide were
      significantly lower than that of the bile duct ligation (P < 0.002). The levels
      of glutathione in resveratrol-treated rats were significantly higher than that in
      bile duct ligation group (P < 0.004). The levels of interleukin-1alpha,
      interleukin-6, and tumor necrosis factor-alpha in resveratrol group were
      significantly lower than that in bile duct ligation group (P < 0.004, P < 0.001,
      P < 0.001, respectively). Administration of resveratrol in the rats with biliary
      obstruction resulted in inhibition of ductular proliferation and lymphocytic
      inflammation. CONCLUSION: The present study demonstrates that intraperitoneal
      administration of resveratrol in bile duct ligated rats maintained antioxidant
      defenses and reduces liver oxidative damage and ductular proliferation. This
      effect of resveratrol may be useful in the preservation of liver function in
      cholestasis.

PMID- 16083750
TI  - Differential expression of immunoglobulin kappa chain constant region in human
      abdominal aortic aneurysm.
AB  - BACKGROUND: A number of the research into the pathogenesis of the abdominal
      aortic aneurysm (AAA) have focused on the alteration of gene expression. The
      current technique for elucidating alterations of gene expression has a setback in
      that many artifact complementary DNA (cDNA) products present abnormal polymerase
      chain reaction (PCR) amplification. Our study was designed to identify
      differentially expressed genes in AAA using the annealing control primer (ACP)
      system, which was recently developed to identify only authentic genes. MATERIALS
      AND METHODS: The tissues of the human abdominal aorta were obtained from the
      patients of AAA and aortic occlusive disease (AOD), and normal abdominal aorta
      (NA) from brain death donors. Total RNAs were isolated from three groups of human
      abdominal aorta (10 AAA, five NA, three AOD) and then reverse transcribed into
      complementary DNA (cDNA). The ACP method was done to screen the difference in the
      expression pattern of the mRNA (mRNA). RESULTS: One differentially expressed cDNA
      band was detected in AAA but not in NA and AOD. This cDNA was sequenced and
      computer searching against the GenBank revealed that the cDNA had more than 90%
      identity with the immunoglobulin kappa chain constant region (Ig kappa-C).
      DISCUSSION: Our finding suggests that differentially expressed Ig kappa-C gene
      only in AAA is a candidate gene that may play a pivotal role in the pathogenesis
      of AAA formation. The correlation of mRNA level and protein level is, however,
      not clear. Thus, to directly identify the role of Ig light chains in the
      pathogenic event of AAA, the further study comparing the level and kinds of
      expressed protein with the corresponding Ig kappa-C gene will be required.

PMID- 16083751
TI  - Vitamin E succinate decreases lung cancer tumor growth in mice.
AB  - BACKGROUND: In vitro studies have shown that Vitamin E succinate (VES) arrests
      lung cancer proliferation; however, in vivo studies have not been performed. This
      study examined in vivo effects of VES on lung cancer. METHODS: An in vitro dose
      response curve of human A549 lung cancer tumors to VES was established. A549
      tumors were established in the right submammary fat pads of athymic nude mice
      (C57/BL/6J-Hfh11nu). Seven days after injection, mice were separated into VES and
      control groups. VES mice (n = 12) underwent daily intraperitoneal (IP) injection
      of VES (150 mg/kg in 7% dimethyl sulfoxide, 93% polyethylene glycol); control
      mice (n = 11) were injected with vehicle only. At 27 days, harvested tumors were
      measured and weighed. Lungs were stained for metastases using hematoxylin-eosin.
      Tumor volume and weights were compared using a two-sample t test. Tumor growth
      curves were compared using a mixed model analysis of variance. RESULTS: In vitro
      studies demonstrated dose-dependent manner inhibition of A549 cell proliferation
      by VES (IC(50) 18 mug/mL). Tumor volumes and weights differed significantly
      between VES and control mice with volumes of 192.6 +/- 20.4 mm(3)versus 292.9 +/-
      31.4 mm(3) (P = 0.01) and weights of 168.6 +/- 20.0 mg versus 255.7 +/- 37.0 mg,
      respectively (P = 0.05). Tumor growth differed significantly (P < 0.001). Both
      groups of mice showed pulmonary metastases. CONCLUSIONS: Lung cancer cells appear
      to respond to VES, albeit incompletely. Because tumor cell response is seen, lung
      cancer patients may derive some benefit from VES and should be considered in
      eventual clinical studies using this vitamin E derivative.

PMID- 16083752
TI  - Matrix metalloproteinases participate in osteosarcoma invasion.
AB  - BACKGROUND: Osteosarcoma (OS) is a highly malignant bone tumor and is the most
      frequent malignant bone tumor in children and adolescents. Metastases are the
      major cause of death, and patients with relapse have poor prognosis. Several
      solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and
      recently MMP-inhibitors have entered clinical trials. A disturbance of the MMP
      system in favor of enhanced proteolytic activity may be suspected in OS because
      OS growth is accompanied by both enhanced local bone destruction and bone
      formation, two processes that are dependant on proteolytic enzymes. Thus, the aim
      of the present study was to evaluate the involvement of MMPs in a panel of human
      OS cell lines, xenografts and biopsies. MATERIAL AND METHODS: Expression of MMPs
      and their endogenous inhibitors were studied by zymography and Northern blot
      analyses. In vitro invasion of OS cell lines and effects of MMP-inhibitors
      (Marimastat and doxycycline) were assessed in the transwell chamber assay.
      RESULTS: In vitro invasiveness was compared with gelatinase activity, and the
      most invasive cell line secreted the highest amounts of MMP-2 and MMP-9. Two
      different MMP-inhibitors significantly reduced OS cell invasion. The majority of
      the OS xenografts expressed both the inactive and active form of MMP-2 and in
      some cases also MMP-9. The biopsies from primary and metastatic OS also expressed
      MMP-2 mRNA. However, MMP-9 levels were higher in the biopsies than in the
      xenografts. CONCLUSION: The obtained results support the hypothesis that MMPs and
      their endogenous inhibitors participate in the invasive process of human OS.

PMID- 16083753
TI  - N-acetylcysteine attenuates bacterial translocation after partial hepatectomy in
      rats.
AB  - BACKGROUND: Translocating enteric bacteria have been suggested as playing a major
      role in the development of infections after partial hepatectomy. We investigated
      the effect of N-acetylcysteine (NAC) on bacterial translocation (BT) and
      intestinal mucosa as the first line of defense against BT. MATERIALS AND METHODS:
      We compared four groups of eight Sprague-Dawley male rats each: sham, control
      (partially hepatectomized), partial hepatectomy plus preoperative single-dose
      NAC, and a fourth that received partial hepatectomy with a preoperative single
      dose NAC plus treatment with NAC for 2 days. Microorganism counts of tissues,
      lung injury score, lung tissue glutathione, and malondialdehyde levels and
      microscopy of intestinal mucosa were studied at the end of 48 h. RESULTS:
      Microorganism count in the lung and mesenteric lymph node cultures and lung
      injury score were significantly higher in the control group when compared with
      the sham, third, and fourth groups (lung: 9919.6 versus 0.0, 2912.9, 1550.0 cfu/g
      tissue; mesenteric lymph nodes: 8458.3 versus 0.0, 89.0, 88.9 cfu/g tissue; lung
      injury score: 3.25 versus 0.5, 1.13, 1.75). In the control group, the villous
      height of the distal ileal mucosa was significantly shorter than the sham group
      (65.25 versus 75.25 microm) and the difference from groups 3 and 4 was not
      statistically significant. Neutrophil infiltration in the distal ileal mucosa of
      the control group was significantly higher than the sham, third and fourth groups
      (3.13 versus 0.25, 0.38 and 1.0). CONCLUSIONS: The parenteral use of NAC
      attenuates bacterial translocation after partial hepatectomy in rats. Attenuation
      of the lung injury after partial hepatectomy in NAC-treated groups might be
      attributable to both anti-inflammatory effect and the effect on BT.

PMID- 16083754
TI  - The effect of growth hormone on gut mucosal homeostasis and cellular mediators
      after severe trauma.
AB  - BACKGROUND: Gut mucosal integrity and function is impaired after severe trauma
      with associated increases in small bowel epithelial cell apoptosis and decreases
      in cell proliferation. Growth hormone improves gastrointestinal function during
      chemotherapy and has anabolic effects on protein synthesis. The purpose of this
      study was to determine whether growth hormone can improve small bowel homeostasis
      after injury and by which cellular mechanisms these changes occur. MATERIALS AND
      METHODS: Rats were pair-fed, given a thermal trauma, and received saline (n = 28)
      or GH (2.5 mg/kg every 24 h, n = 28). Small intestine and serum were taken at 1,
      2, 5, and 7 days after injury. Measures were mucosal apoptosis, proliferation,
      villous morphology, apoptotic, and proliferative mediators, such as Caspases-3, 
      8, Fas and Fas-Ligand, Bcl-2, and Bcl-x. In addition serum cytokines were
      determined. RESULTS: Gut epithelial cell apoptosis and proliferation were
      increased in both groups after the thermal injury (P < 0.05). GH had neither an
      effect on small bowel epithelial cell apoptosis or proliferation, nor dependent
      cellular mediators after thermal injury. However, GH significantly improved
      villous morphology (height and cell number) when compared with controls (P <
      0.05). RhGH was found to significantly increase serum TNF-alpha compared to
      controls (P < 0.05). CONCLUSION: Growth hormone improves small bowel homeostasis
      after severe trauma independent from small bowel epithelial cell apoptosis or
      proliferation, probably by increasing the life span.

PMID- 16083755
TI  - The nutritional status modulates preservation-reperfusion injury in rat fatty
      liver.
AB  - BACKGROUND: Microcirculation disturbances are essential factors of preservation
      injury in fatty liver. However, hepatocyte injury is also markedly excessive in
      fatty liver resulting, at least in part, from energy metabolism impairment and
      oxidative stress. Thus, this study aimed to determine whether nutritional status
      influences preservation injury in fatty liver and whether energetic substrate
      supplementation, alone or with a vasodilator, is protective. MATERIALS AND
      METHODS: Normal or fatty livers induced by a choline-deficient diet were isolated
      from fed and fasted rats, preserved in University of Wisconsin solution at 4
      degrees C for 18 h, and then reperfused with Krebs-Henseleit solution at 37
      degrees C for 120 min. Fasted rats with fatty liver were also treated as follows:
      (1) Glucose supplementation: rats had access to a glucose solution for 18 h prior
      procurement; (2) Prostaglandin (PG): alprostadil was continuously infused during
      reperfusion; (3) Combined treatment: Glucose supplementation + PG. RESULTS:
      Fasting-induced liver injury was significantly greater in fatty than normal
      liver. In fatty livers from fasted rats, all treatments reduced the alanine
      aminotransaminase release. Hepatic oxygen consumption improved in the glucose and
      glucose + PG groups, while PG infusion had no effect. Glucose supplementation did
      not affect portal pressure, which, in contrast, was reduced in livers receiving
      PG. Finally, all treatments lowered oxidative injury. CONCLUSIONS: Preservation
      injury in fatty liver is greatly related to nutritional status. Energetic
      substrate supplementation may represent a clinically feasible protective strategy
      and a multistep approach adding vasodilators could offer further benefit by
      acting on different pathogenetic mechanisms.

PMID- 16083756
TI  - Mechanisms of focal heat destruction of liver tumors.
AB  - BACKGROUND: Focal heat destruction has emerged as an effective treatment strategy
      in selected patients with malignant liver tumors. Radiofrequency ablation,
      interstitial laser thermotherapy, and microwave treatment are currently the most
      widely applied thermal ablative techniques. A major limitation of these therapies
      is incomplete tumor destruction and overall high recurrences. An understanding of
      the mechanisms of tissue injury induced by focal hyperthermia is essential to
      ensure more complete tumor destruction. Here, the currently available scientific
      literature concerning the underlying mechanisms involved in the destruction of
      liver tumors by focal hyperthermia is reviewed. METHODS: Medline was searched
      from 1960 to 2004 for literature regarding the use of focal hyperthermia for the
      treatment of liver tumors. All relevant literature was searched for further
      references. RESULTS: Experimental evidence suggests that focal hyperthermic
      injury occurs in two distinct phases. The first phase results in direct heat
      injury that is determined by the total thermal energy applied, tumor biology, and
      the tumor microenvironment. Tumors are more susceptible to heat injury than
      normal cells as the result of specific biological features, reduced heat
      dissipating ability, and lower interstitial pH. The second phase of hyperthermic
      injury is indirect tissue damage that produces a progression of tissue injury
      after the cessation of the initial heat stimulus. This progressive injury may
      involve a balance of several factors, including apoptosis, microvascular damage,
      ischemia-reperfusion injury, Kupffer cell activation, altered cytokine
      expression, and alterations in the immune response. Blood flow modulation and
      administration of thermosensitizing agents are two methods currently used to
      increase the extent of direct thermal injury. The processes involved in the
      progression of thermal injury and therapies that may potentially modulate them
      remain poorly understood. CONCLUSION: Focal hyperthermia for the treatment of
      liver tumors involves complex mechanisms. Evidence suggests that focal
      hyperthermia produces both direct and indirect tissue injury by differing
      underlying processes. Methods to enhance the effects of treatment to achieve
      complete tumor destruction should focus on manipulating these processes.

PMID- 16083757
TI  - Screening of organic halogens and identification of chlorinated benzoic acids in
      carbonaceous meteorites.
AB  - The occurrence of halogenated organic compounds measured as a sum parameter and
      the evidence of chlorinated benzoic acids in four carbonaceous meteorites (Cold
      Bokkeveld, Murray, Murchison and Orgueil) from four independent fall events is
      reported. After AOX (Adsorbable organic halogen) and EOX (Extractable organic
      halogen) screening to quantify organically bound halogens, chlorinated organic
      compounds were analyzed by gas chromatography. AOX concentrations varying from
      124 to 209 microg Cl/g d.w. were observed in carbonaceous meteorites. Ion
      chromatographic analysis of the distribution of organically bound halogens
      performed on the Cold Bokkeveld meteorite revealed that chlorinated and
      brominated organic compounds were extractable, up to 70%, whereas only trace
      amounts of organofluorines could be extracted. Chlorinated benzoic acids have
      been identified in carbonaceous meteorite extracts. Their presence and
      concentrations raise the question concerning the origin of halogenated,
      especially chlorinated, organic compounds in primitive planetary matter.

PMID- 16083758
TI  - Pencycuron application to soils: degradation and effect on microbiological
      parameters.
AB  - Clay loam soil from agricultural fields of alluvial (AL) soil (typic udifluvent)
      and coastal saline (CS) soil (typic endoaquept) were investigated for the
      degradation and effect of pencycuron application at field rate (FR), 2-times FR
      (2FR) and 10-times FR (10FR) with and without decomposed cow manure (DCM) on soil
      microbial variables under laboratory conditions. Pencycuron degraded faster in CS
      soil and in soil amended with DCM. Pencycuron spiking at FR and 2FR resulted in a
      short-lived (in case of 10FR slightly longer) and transitory toxic effect on soil
      microbial biomass-C (MBC), ergosterol content and fluorescein diacetate
      hydrolyzing activity (FDHA). Amendment of DCM did not seem to have any
      counteractive effect of the toxicity of pencycuron on the microbial variables.
      The ecophysiological status of the soil microbial communities as expressed by
      microbial metabolic quotient (qCO2) and microbial respiration quotient (Q(R))
      changed, but for a short period, indicating pencycuron induced disturbance. The
      duration of this disturbance was slightly longer at 10FR. Pencycuron was more
      toxic to the metabolically activated soil microbial populations, specifically the
      fungi. It is concluded that side effects of pencycuron at 10FR on the microbial
      variables studied were only short-lived and probably of little ecological
      significance.

PMID- 16083759
TI  - Phototransformation of methabenthiazuron in the presence of nitrate and nitrite
      ions.
AB  - The influence of nitrate and nitrite ions on the degradation of
      methabenzthiazuron upon irradiation using artificial solar light has been
      investigated. The rate of degradation of methabenzthiazuron (1 microM) was
      accelerated by NO3- (0.1 mM) by a factor of 10. The irradiation of
      methabenzthiazuron (0.1 mM) in the presence of NO3- (1 mM) or NO2- (0.1 mM)
      yielded numerous intermediary photoproducts. Mineralization was achieved after
      prolonged exposure. Some were identified with the help of LC-ESI-MS and flow
      injection APCI-MS techniques. Both oxidations of the aromatic ring and of the
      urea chain were observed. The former started by hydroxylation of the ring.
      Further oxidation of the ring led to cleavage of the benzenic ring with formation
      of dialdehydic, diacidic and anhydric compounds. Complete removal of the lateral
      urea chain took place subsequently to demethylation of the terminal methyl group
      and loss of the CO-NH2 group. Nitration was a minor process. This work shows that
      the photodegradation of methabenzthiazuron in the presence of nitrate or nitrite
      ions is highly non-specific.

PMID- 16083760
TI  - Organochlorinated pesticides in sediments from the Lake Albufera of Valencia
      (Spain).
AB  - Bottom sediment samples from 121 sites of the Lake Albufera of Valencia were
      analyzed. Dieldrin, endrin, heptachlor and op'-DDT were not detected (<0.01 ng g(
      1)) in 88-93% of the sites. Aldrin and HCB concentration ranges were between
      <0.01 and 0.1 ng g(-1) in 86% and 94% of the sites, respectively. Heptachlor
      epoxide and lindane 95% confidence intervals were 0.2-0.5 and 0.06-0.12,
      respectively. The greatest average concentration corresponds to pp'-DDE, pp'-DDD
      and pp'-DDT. The sum of six isomers and derivatives of the DDT average
      concentration reaches 2.1 ng g(-1), as opposed to 2.7 ng g(-1) for the sum of 13
      pesticides considered. In the site with a major contamination, 27.0 ng g(-1) of
      pp'-DDD and 12.8 ng g(-1) of pp'-DDT were accumulated. The DDE:DDT proportion
      average was 0.37, indicating an aged DDT contamination. Concentrations of
      pesticides in sediments were compared to three sediment quality guidelines, and
      indicated that a low biological effects level can be expected in either sediments
      or aquatic organisms.

PMID- 16083761
TI  - Aerobic biodegradation of vinyl chloride and cis-1,2-dichloroethylene in aquifer
      sediments.
AB  - Laboratory batch experiments have been performed with sediment and groundwater
      obtained from two sites in Denmark to study the aerobic biodegradation of vinyl
      chloride (VC) and cis-1,2-dichloroethylene (c-1,2-DCE) to assess the natural
      aerobic biodegradation potential at two sites. The experiments revealed that VC
      was degraded to below the detection limit within 204 and 57 days at the two
      sites. c-1,2-DCE was also degraded in the experiments but not completely. At the
      two sites 50% and 35% was removed by the end of the experimental period of 204
      and 274 days. The removal of c-1,2-DCE seems to occur concomitantly with VC
      indicating that the biodegradation of c-1,2-DCE may depend on the biodegradation
      of VC. However, in both cases natural groundwater was mixed with sediment and
      consequently there may be other compounds (e.g. ammonium, natural organic
      compound etc.) that serves as primary substrates for the co-metabolic
      biodegradation of c-1,2-DCE. At one of the sites methane was supplied to try to
      enhance the biodegradation of VC and c-1,2-DCE. That was successful since the
      time for complete biodegradation of VC decreased from 204 days in the absence of
      methane to 84 days in the presence of methane. For c-1,2-DCE the amount that was
      biodegraded after 204 days increased from 50% to 90% as a result of the addition
      of methane. It seems like a potential for natural biodegradation exists at least
      for VC at these two sites and also to some degree for c-1,2-DCE.

PMID- 16083762
TI  - Electrochemical analysis of endosulfan using a C18-modified carbon-paste
      electrode.
AB  - Successful applications of different analytical procedures to determine
      quantitatively endosulfan and its metabolites in aqueous media can be found in
      recent literature. Fundamentally, they have made use of solid-phase extraction
      (SPE) and gas (GC) or liquid chromatography (LC), sometimes coupled to mass
      spectrometry (MS). In this paper, a new and alternative methodology to determine
      quantitatively endosulfan in aqueous media is reported. A C18-modified carbon
      paste electrode has been used to determine voltammetrically endosulfan, despite
      its unfavourable electrochemical properties and behaviour. The methodology
      proposed is based on the decrease experienced by the peak intensity corresponding
      to voltammetric signals of Cu(II) when successive and constant additions of
      endosulfan are carried out. This decrease is directly proportional to the
      concentration of endosulfan what allows to perform an indirect quantification of
      the pesticide. The detection limit obtained is 40 ng l(-1), this value being
      under the limits specified by European norms and EPA reports.

PMID- 16083763
TI  - Oxygenated fuel induced cosolvent effects on the dissolution of polynuclear
      aromatic hydrocarbons from contaminated soil.
AB  - The cosolvent-induced dissolution of polynuclear aromatic hydrocarbons (PAHs)
      from contaminated soil caused by oxygenated fuel spills was studied. Oxygenated
      fuel induces a solvent flushing effect on the contaminated soil due to the high
      content of oxygenated compounds (i.e., methanol, ethanol, and methyl tert butyl
      ether (MTBE)). The miscible displacement techniques were applied to evaluate the
      increased potential for secondary contamination in an impacted site. Significant
      solubility enhancement of the 18 PAHs monitored during fuel spill simulation and
      cosolvent flushing is clearly evident when compared to normal water dissolution.
      The breakthrough concentration profile for each PAH constituent was integrated
      over the cumulative effluent volume (i.e., the zeroth moment) to determine the
      total PAH mass removed during the experiment. The removal efficiency of PAHs
      ranges from 46.6% to 99.9% in three oxygenated fuels (i.e., M85, E85, and
      oxygenated gasoline) during the fuel spill. Several factors including
      hydrophobicity of compounds, nonequilibrium dissolution due to nonuniform coal
      tar distribution, and heterogeneous media properties affect the oxygenated
      compound-induced dissolution process. This study provides a basis to predict the
      facilitated transport of hydrophobic organic compounds from subsurface
      environment due to the cosolvent effects of oxygenated fuels.

PMID- 16083764
TI  - Sorption of mercury (II) in Amazon soils from column studies.
AB  - The sorption of Hg (II) onto four different types of Amazon soils from the A
      horizon was investigated by means of column experiments under saturation
      conditions and controlled metal load. Higher organic matter contents in the soil
      resulted in higher Hg (II) adsorptions, reaching values as high as 3.8 mg Hg g(
      1) soil. The amount of mercury adsorbed on a soil column (Q) shows a very poor
      correlation with soil clay content (r2 = 0.2527), indicating that Hg sorption in
      these topsoil samples is chiefly governed by the organic matter content.
      Desorption experiments using Negro River (Amazon) waters were conducted using
      soil saturated with Hg (II) in order to better understand the metal leaching
      mechanism. The amount of Hg (II) released from soils was around 30% of the total
      sorbed mercury upon saturation, suggesting that mercury sorption in the soils
      present in the catchment area of the Negro River basin is not a reversible
      process.

PMID- 16083765
TI  - Distribution of pesticides and heavy metals in trophic chain.
AB  - Determination of triazines herbicides (atrazine and simazine) by high performance
      liquid chromatography (HPLC) in samples of trophic chain were worked out.
      Determination limits of 0.5 microg g(-1) for atrazine, 0.8 microg g(-1) for
      simazine with pesticides recovery of 70-77% in trophic chain samples were
      obtained. The content of simazine in soils was in range 1.72-57.89 microg g(-1),
      in grass 5-88 microg g(-1), in milk 2.32-15.29 microg g(-1), in cereals 10.98-387
      microg g(-1), in eggs 30.14-59.48 microg g(-1), for fruits: 2.45-6.19 microg g(
      1). The content of atrazine in soils was in range 0.69-19.59 microg g(-1), in
      grass 7.85-23.85 microg g(-1), in cereals 1.88-43.08 microg g(-1). Cadmium, lead
      and zinc were determined by inductively coupled plasma atomic emission
      spectrometry (ICP-AES) in the same samples as atrazine and simazine.
      Determination limits for cadmium 5 x 10(-3) microg g(-1), for lead 1 x 10(-2)
      microg g(-1), and for zinc 0.2 x 10(-3) microg g(-1), were obtained. The content
      of cadmium in soil was in range 0.13-5.89 microg g(-1), in grass 114-627.72 x 10(
      3) microg g(-1), in milk 8.88-61.88 x 10(-3) microg g(-1), in cereals 0.20-0.31
      microg g(-1), in eggs 0.11-0.15 microg g(-1), in fruits 0.23-0.59 microg g(-1).
      The content of lead in soils was in range 0.57-151.50 microg g(-1), in grass 0.16
      136.57 microg g(-1), in milk 1.16-3.74 microg g(-1), in cereals 1.05-5.47 microg
      g(-1), in eggs 5.79-55.87 microg g(-1), in fruits 21.00-87.36 microg g(-1). Zinc
      content in soil was in range 9.15-424.5 microg g(-1), in grass 35.20-55.87 microg
      g(-1), in milk 20.00-34.38 microg g(-1), in cereals 14.94-28.78 microg g(-1), in
      eggs 15.67-32.01 microg g(-1), in fruits 14.94-18.88 microg g(-1). Described
      below extraction and mineralization methods for particular trophic chains allowed
      to determine of atrazine, simazine, cadmium, lead and zinc with good
      repeatability and precision. Emphasis was focused on liquid-liquid extraction and
      solid-phase extraction of atrazine and simazine from analysed materials, as well
      as, on monitoring the content of herbicides and metals in soil and along trophic
      chain. Higher concentration of pesticides in samples from west region of Poland
      in comparison to that of east region is likely related to common applying them in
      Western Europe in relation to East Europe. The content of metals strongly depends
      on samples origin (industry area, vicinity of motorways).

PMID- 16083766
TI  - Adsorption kinetics and isotherms of pesticides onto activated carbon-cloth.
AB  - Adsorption of pesticides ametryn, aldicarb, dinoseb and diuron from aqueous
      solution onto high specific area activated carbon-cloth was studied. Kinetics of
      adsorption was followed by in situ UV-spectroscopy and the data were treated
      according to various rate models. The extent of adsorption was determined at the
      end of 125 min adsorption period. Rate constants and the extent of adsorption for
      the four pesticides were found to follow the order: dinoseb > ametryn > diuron >
      aldicarb. Adsorption isotherms were derived at 25 degrees C on the basis of batch
      analysis. Isotherm data were treated according to Langmuir and Freundlich models.
      The fits of experimental data to these equations were examined. The types of
      interactions between the surface and pesticide molecules were discussed.

PMID- 16083767
TI  - Dissolved organic matter in pore water of freshwater sediments: effects of
      separation procedure on quantity, quality and functionality.
AB  - Pore water was separated either with or without water extraction prior to
      centrifugation (7600 or 20,000 x g) in order to investigate the effects of
      separation procedure on the amount and properties of dissolved organic matter
      (DOM i.e. the material passing through a 0.45-microm filter) in three freshwater
      sediments. On the basis of solubility in alkaline, organic matter was concluded
      to compose of humic substances in two (S1 and S3) and of humin (S2) in one of the
      sediments. DOM in the samples was quantified by total organic carbon measurement.
      Specific UV-absorption (SUVA) and high performance size exclusion chromatography
      (HPSEC) analyses were used to characterize DOM. Sorption of pyrene was used as a
      measure for functionality of DOM. Both water extraction and centrifugation speed
      were shown to affect the properties of DOM; however, the effects were sediment
      dependent. Water extraction increased the amount of DOM separated from the two
      sediments that had humic character (S1 and S3). In most cases water extraction
      increased SUVA and shifted the molecular size distribution of DOM towards larger
      sizes. The separation procedure had also an effect on the functionality of DOM.
      In water extracted samples of S2 and S3 the sorption of pyrene was higher than in
      the corresponding samples separated without water extraction, whereas in S1
      similar effect was not found. Generally, centrifugation speed had smaller effects
      on the properties of DOM than water extraction. The fact that the effects of
      separation procedure on DOM depend on the sediment characteristics complicates
      the comparison between samples and evaluation of functionality in field
      conditions.

PMID- 16083768
TI  - Kinetic studies of adsorption of thiocyanate onto ZnCl2 activated carbon from
      coir pith, an agricultural solid waste.
AB  - The adsorption of thiocyanate onto ZnCl2 activated carbon developed from coir
      pith was investigated to assess the possible use of this adsorbent. The influence
      of various parameters such as agitation time, thiocyanate concentration,
      adsorbent dose, pH and temperature has been studied. Adsorption followed second
      order rate kinetics. Two theoretical adsorption isotherms, namely, Langmuir and
      Freundlich were used to describe the experimental results. The Langmuir
      adsorption capacity (Q0) was found to be 16.2 mg g(-1) of the adsorbent. The per
      cent adsorption was maximum in the pH range 3.0-7.0. pH effect and desorption
      studies showed that ion exchange and chemisorption mechanism are involved in the
      adsorption process. Thermodynamic parameters such as DeltaG0, DeltaH0 and DeltaS0
      for the adsorption were evaluated. The negative values of DeltaH0 confirm the
      exothermic nature of adsorption. Effects of foreign ions on the adsorption of
      thiocyanate have been investigated. Removal of thiocyanate from ground water was
      also tested.

PMID- 16083769
TI  - Synthesis of branched para-nonylphenol isomers: occurrence and quantification in
      two commercial mixtures.
AB  - Eight tertiary nonanols were synthesized via Grignard reaction and coupled by
      Friedel-Crafts alkylation with phenol to the corresponding nonylphenols. Six
      branched para-nonylphenols (NP) were obtained: 4-(3'-methyl-3'-octyl)phenol
      (33NP), 4-(2'-methyl-2'-octyl)phenol (22NP), 4-(2',5'-dimethyl-2'-heptyl)phenol
      (252NP), 4-(2',5',5'-trimethyl-2'-hexyl)phenol (2552NP), 4-(2',4'-dimethyl-2'
      heptyl)phenol (242NP) and 4-(4'-ethyl-2'-methyl-2'-hexyl)phenol (4E22NP). Their
      structures were confirmed by GC-MS and NMR spectroscopy. These six isomers as
      well as the earlier synthesized 4-(3',5'-dimethyl-3'-heptyl)phenol (353NP), 4
      (3',6'-dimethyl-3'-heptyl)phenol (363NP) and 4-(2',6'-dimethyl-2'-heptyl)phenol
      (262NP) were compared with commercial NP mixtures purchased from Acros and Fluka
      by GC-MS (equipped with a 100 m polysiloxane column). The analyses revealed that
      all obtained isomers are occurring in different quantities in both commercial NP
      mixtures.

PMID- 16083770
TI  - Anaerobic digestion of linear alkyl benzene sulfonates: biodegradation kinetics
      and metabolite analysis.
AB  - In the present work the effect of the alkyl chain length and the position of the
      sulfophenyl substituent of the linear alkylbenzene sulfonates (LAS) on their
      anaerobic biodegradability have been investigated. Degradation kinetics of the
      linear alkyl benzene sulfonates homologues, 2phiC10LAS, 2phiC12LAS and
      2phiC14LAS, have been studied. It has been also investigated the effect of the
      isomer type on the degradation rate of the LAS molecule through the comparative
      study of the 2phiC10LAS and 5phiC10LAS isomers. Batch anaerobic biodegradation
      tests were performed using sludge from the anaerobic digester of a wastewater
      treatment plant as microorganisms source. Ultimate biodegradation was evaluated
      from the biogas production whereas primary biodegradation was determined by
      specific analysis of the surfactant. LAS homologues and isomers showed a
      negligible primary biodegradation under anaerobic conditions. Furthermore,
      analysis of sulfophenyl carboxilates (SPC) by LC-MS indicated a low and constant
      level of these LAS degradation metabolites over the test period. These data are
      consistent with a minimal transformation of the LAS parent molecule in the
      anaerobic digesters. On the other hand, the addition of the shortest alkyl chain
      length homologues, decyl and dodecylbenzene sulfonates, reduces the biogas
      production whereas the most hydrophobic homologue, the tetradecylbenzene
      sulfonate, enhances the biogas production. This LAS homologue seems to increase
      the availability of organic compounds sorbed on the anaerobic sludge promoting
      their biodegradation.

PMID- 16083771
TI  - Brominated-chlorinated diphenyl ethers formed by thermolysis of polybrominated
      diphenyl ethers at low temperatures.
AB  - Polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardants
      (BFRs) used mainly as additives in different kinds of plastic material. Various
      PBDEs are found in all environmental compartments as well as in tissue and blood
      serum of animals and humans due to their persistence and tendency to
      bioaccumulate. Emission of PBDEs into the environment can occur during recycling
      of PBDE-containing plastic material or during their uncontrolled or insufficient
      combustion as e.g. in accidental fires or landfill fires. Under these
      circumstances, PBDEs can also function as precursor molecules for the formation
      of polybrominated dibenzodioxins (PBDDs) and dibenzofurans (PBDFs). In this
      study, we qualitatively investigated the reaction of two PBDE congeners,
      2,2',4,4'-tetrabromo diphenyl ether (BDE 47) and 2,2',4,4',5,5'-hexabromo
      diphenyl ether (BDE 153), as well as hexabromobenzene (HBB), a flame retardant
      used in the past, when exposed to temperatures between 250 degrees C and 500
      degrees C. The formed reaction products were analysed by high resolution gas
      chromatography-low resolution mass spectrometry (HRGC-LRMS). Among others
      brominated-chlorinated diphenyl ethers were formed by chlorodebromination of the
      PBDEs. In addition, thermolysis of BDE 47 and BDE 153 in the presence of
      tetrachloromethane as model substance for an organic chlorine source was studied.
      Thermal treatment of HBB resulted in the formation of brominated-chlorinated
      benzenes.

PMID- 16083772
TI  - Biodegradation of nonylphenol in sewage sludge.
AB  - We investigated the effects of various factors on the aerobic degradation of
      nonylphenol (NP) in sewage sludge. NP (5 mg/kg) degradation rate constants (k1)
      calculated were 0.148 and 0.224 day(-1) for the batch experiment and the
      bioreactor experiment, respectively, and half-lives (t(1/2)) were 4.7 and 3.1
      days, respectively. The optimal pH value for NP degradation in sludge was 7.0 and
      the degradation rate was enhanced when the temperature was increased and when
      yeast extract (5 mg/l) and surfactants such as brij 30 or brij 35 (55 or 91
      microM) were added. The addition of aluminum sulfate (200 mg/l) and hydrogen
      peroxide (1 mg/l) inhibited NP degradation within 28 days of incubation. Of the
      microorganism strains isolated from the sludge samples, we found that strain CT7
      (identified as Bacillus sphaericus) manifested the best degrading ability.

PMID- 16083773
TI  - Composition of torched crude oil organic particulate emitted by refinery and its
      similarity to atmospheric aerosol in the surrounding area.
AB  - The absolute contents and relative distributions of organic aerosols [n-alkanes,
      n-alkanoic and n-alkenoic acids, n-alkan-2-ones and polycyclic aromatic
      hydrocarbons (PAH)] were determined in torched gases emitted during the crude oil
      extraction and in the free atmosphere of the Hassi-Messaoud city (Algeria).
      Monocarboxylic acids, both saturated and monounsaturated (from 9802 to 20,057 ng
      m(-3)), accounted for the major fraction of the total particulate organic matter
      identified both in torch exhaust and atmospheric particulate. n-Alkanes were also
      abundant both in the direct emission (from 460 to 632 ng m(-3)) and city
      atmosphere (462 ng m(-3)) and displayed a peculiar fingerprint characterised by
      the presence of a set of branched congeners around even carbon-numbered
      homologues and a strong even-to-odd predominance along the whole carbon number
      range (C16-C34). Whilst n-alkan-2-ones were absent in the city and poor in smokes
      emitted from the torches (from 31 to 42 ng m(-3)), PAH were present at low
      extents in all sites (from 18 to 65 ng m(-3)). The incomplete thermal combustion
      of torched crude oil was very likely the main source of these particle-bound
      organic constituents in the city and its surrounding region.

PMID- 16083775
TI  - Innate immune responses to infection.
AB  - The human host survives many infectious challenges in the absence of preexisting
      specific (adaptive) immunity because of the existence of a separate set of
      protective mechanisms that do not depend on specific antigenic recognition. These
      antigen-independent mechanisms constitute innate immunity. Antimicrobial peptides
      are released at epithelial surfaces and disrupt the membranes of many microbial
      pathogens. Toll-like receptors on epithelial cells and leukocytes recognize a
      range of microbial molecular patterns and generate intracellular signals for
      activation of a range of host responses. Cytokines released from leukocytes and
      other cells exhibit a vast array of regulatory functions in both adaptive and
      innate immunity. Chemokines released from infected tissues recruit diverse
      populations of leukocytes that express distinct chemokine receptors. Natural
      killer cells recognize and bind virus-infected host cells and tumor cells and
      induce their apoptosis. Complement, through the alternative and mannose-binding
      lectin pathways, mediates antibody-independent opsonization, phagocyte
      recruitment, and microbial lysis. Phagocytes migrate from the microcirculation
      into infected tissue and ingest and kill invading microbes. These innate immune
      mechanisms and their interactions in defense against infection provide the host
      with the time needed to mobilize the more slowly developing mechanisms of
      adaptive immunity, which might protect against subsequent challenges.

PMID- 16083776
TI  - EBV the prototypical human tumor virus--just how bad is it?
AB  - EBV was the first candidate human tumor virus. It is found in several human
      cancers, particularly lymphomas and carcinomas, and has potent transforming
      activity in vitro. Yet the virus persists benignly for the lifetime of more than
      90% of the human population. Thus it seems that EBV has the potential to be
      highly pathogenic yet rarely manifests this potential. Studies over the last
      several years show this is because the virus actually persists in resting memory
      B cells and not proliferating cells. EBV needs its growth-promoting ability to
      gain access to the memory compartment but has evolved to minimize its oncogenic
      potential. These studies also reveal that the different EBV-associated tumors
      apparently arise from different and discrete stages in the life cycle of B cells
      latently infected with EBV. This raises the question of how actively EBV
      participates in the development of human tumors. Does the virus cause the
      disease, or is it simply a passenger? In the case of immunoblastic lymphoma in
      the immunosuppressed patient, the virus almost certainly plays a causative role,
      but in other cases, such as Burkitt's lymphoma, the contribution of EBV remains
      less clear.

PMID- 16083777
TI  - Infection versus immunity: What's the balance?

PMID- 16083778
TI  - The role of rhinovirus in asthma exacerbations.
AB  - Rhinoviruses are a major cause of asthma exacerbations in children and adults.
      With the use of sensitive RT-PCR methods, respiratory viruses are found in
      approximately 80% of wheezing episodes in children and in approximately one half
      of such episodes in adults. Rhinovirus is a member of the family Picornaviridae,
      and acute rhinovirus infections occur predominantly in the upper airway. This
      virus has also been identified in the lower airway, and it might cause acute
      wheezing through the production of proinflammatory mediators with a resulting
      neutrophilic inflammatory response. Precisely how this process leads to increases
      in airway hyperresponsiveness and airway obstruction is not fully established.
      However, risk factors for wheezing with colds include asthma and atopy, extremes
      in age, and perhaps having a deficient TH1 response to rhinovirus. With the use
      of in vitro models and experimental inoculation studies, significant advances
      have led to a better understanding of the mechanisms by which rhinovirus
      infections cause asthma exacerbations. Advances in our understanding of this
      interaction might provide knowledge that could ultimately lead to specific
      treatment modalities to prevent and/or treat this significant burden of asthma
      exacerbations.

PMID- 16083779
TI  - Perspectives on the past decade of asthma genetics.
AB  - Although genetic linkage and association studies have identified more than 25
      asthma or allergy susceptibility loci, replication of significant results remains
      a problem. Moreover, these approaches typically ignore the true complexity of
      these diseases, such as the role of gene-by-environment and gene-by-gene
      interactions. As a result, many important associations might have been missed.
      Recent studies demonstrate not only that such interactions exist but also that
      the relationship between genotype and phenotype is more complex than previously
      thought.

PMID- 16083780
TI  - Is it traffic type, volume, or distance? Wheezing in infants living near truck
      and bus traffic.
AB  - BACKGROUND: Previous studies of air pollution have not examined the association
      between exposure to varying types, distance, and amounts of traffic and wheezing
      in very young infants. OBJECTIVE: We sought to determine the relationship between
      types of traffic, traffic volume, and distance and wheezing among infants less
      than 1 year of age. METHODS: A geographic information system and a classification
      scheme were developed to categorize infants enrolled in the study as living near
      moving truck and bus traffic (highway >50 miles per hour, >1000 trucks daily,
      <400 m), stop-and-go truck and bus traffic (<50 miles per hour, <100 m), or
      unexposed and not residing near either. Symptom data were based on health
      questionnaires administered to parents when the infants were 6 months of age and
      monthly health diaries. RESULTS: Infants living very near (<100 m) stop-and-go
      bus and truck traffic had a significantly increased prevalence of wheezing
      (adjusted odds ratio, 2.50; 95% CI, 1.15-5.42) when compared with unexposed
      infants. The prevalence of wheezing among nonwhite infants was at least twice
      that of white infants, regardless of exposure. Infants living less than 400 m
      from a high volume of moving traffic, however, did not have an increased
      prevalence of wheezing. CONCLUSION: These results suggest that the distance from
      and type of traffic exposures are more significant risk factors than traffic
      volume for wheezing in early infancy.

PMID- 16083781
TI  - Effect of low-dose ciclesonide on allergen-induced responses in subjects with
      mild allergic asthma.
AB  - BACKGROUND: Inhalation of allergens by sensitized patients with asthma induces
      reversible airway obstruction, airway hyperresponsiveness, and eosinophilic
      airway inflammation. Attenuation of allergen-induced bronchoconstriction and
      inflammation has been used to examine the efficacy of therapeutic agents such as
      inhaled corticosteroids in asthma. Ciclesonide, a nonhalogenated inhaled
      corticosteroid being developed for the treatment of persistent asthma, remains
      inactive until cleaved by esterases in the lung. OBJECTIVE: This study examined
      the effect of low doses of inhaled ciclesonide, 40 microg and 80 microg, on
      allergen-induced bronchoconstriction, serum eosinophil cationic protein, and
      eosinophilic airway inflammation. METHODS: Twenty-one nonsmokers with mild atopic
      asthma completed a multicenter, randomized, 3-way crossover study comparing the
      effects of 7-day treatment of ciclesonide or placebo. Allergen-induced responses,
      including the early and late fall in FEV1, peripheral blood eosinophils, serum
      eosinophil cationic protein levels, and eosinophils in induced sputum were
      measured. RESULTS: Ciclesonide 80 microg attenuated the early and late asthmatic
      responses, including the change in FEV1, serum eosinophil cationic protein, and
      sputum eosinophils measured at 24 hours postchallenge (P < .025). Ciclesonide 40
      microg attenuated the late asthmatic responses and sputum eosinophils measured at
      24 hours postchallenge (P < .025), with no effect on the early allergen-induced
      bronchoconstriction, 24-hour FEV1, or serum eosinophil cationic protein levels (P
      < .025). CONCLUSION: With the exception of 24-hour postchallenge peripheral blood
      eosinophils, a low dose of ciclesonide, 80 microg, was effective in blocking all
      allergen-induced responses measured.

PMID- 16083782
TI  - Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates
      allergen-induced asthmatic reactions.
AB  - BACKGROUND: Asthma is a chronic inflammatory disease with increasing incidence
      worldwide. Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type
      4 that prevents the breakdown of cyclic adenosine monophosphate levels, leading
      to inhibition of proinflammatory signaling. OBJECTIVE: The objective of this
      study was to investigate the effects of repeated doses of 250 or 500 microg of
      roflumilast on asthmatic airway responses to allergen. METHODS: Twenty-three
      patients with mild asthma with an FEV1 of 70% of predicted value or greater were
      enrolled in a randomized, double-blind, placebo-controlled, 3-period crossover
      study. Patients participated in 3 treatment periods (7-10 days) separated by
      washout periods (2-5 weeks). Patients received 250 microg of oral roflumilast,
      500 microg of roflumilast, or placebo once daily. Allergen challenge was
      performed at the end of each treatment period, followed by FEV1 measurements over
      the ensuing 24 hours. RESULTS: Late asthmatic reactions (LARs) were reduced by
      27% (P = .0110) and 43% (P = .0009) in patients treated with 250 and 500 microg
      of roflumilast, respectively, versus placebo. Roflumilast, 250 and 500 microg,
      also attenuated early asthmatic reactions by 25% (P = .0038) and 28% (P = .0046),
      although not to the same extent as LAR attenuation. Roflumilast was well
      tolerated. No serious adverse events or discontinuations caused by adverse events
      were reported. CONCLUSION: Once-daily oral roflumilast modestly attenuated early
      asthmatic reactions and, to a greater extent, LARs to allergen in patients with
      mild allergic asthma. Pronounced suppression of late responses in an allergen
      challenge model suggests that roflumilast might have anti-inflammatory activity,
      which could provide clinical efficacy in chronic inflammatory pulmonary diseases,
      such as asthma.

PMID- 16083783
TI  - Duration of postviral airway hyperresponsiveness in children with asthma: effect
      of atopy.
AB  - BACKGROUND: Respiratory viruses induce asthma exacerbations and airway
      hyperresponsiveness (AHR). Atopy is an important risk factor for asthma
      persistence. OBJECTIVE: We sought to evaluate whether atopy is a risk factor for
      prolonged AHR after upper respiratory tract infections (URIs). METHODS: Twenty
      five children (13 atopic and 12 nonatopic children) with intermittent virus
      induced asthma were studied. Clinical evaluation, skin prick tests, methacholine
      bronchoprovocation, questionnaires, and a nasal wash specimen were obtained at
      baseline. For 9 months, subjects completed diary cards with respiratory symptoms.
      During their first reported cold, a nasal wash specimen was obtained.
      Methacholine provocation was performed 10 days and 5, 7, 9, and 11 weeks later.
      In case a new cold developed, the provocation schedule was followed from the
      beginning. RESULTS: Viruses were detected in 17 (68%) of 25 patients during their
      first cold, with rhinovirus being most commonly identified (82%). AHR increased
      significantly 10 days after the URI, equally in both groups (P = .67), and
      remained so up to the fifth week. Duration of AHR in subjects experiencing a
      single URI ranged from 5 to 11 weeks, without a significant difference between
      groups. In the duration of the study, atopic children experienced more colds and
      asthma exacerbations than nonatopic children. Thus for duration of AHR,
      significant prolongation was noted in the atopic group when assessed
      cumulatively. CONCLUSION: In asthmatic children the duration of AHR after a
      single natural cold is 5 to 11 weeks. However, an increased rate of symptomatic
      cold and asthma episodes in atopic children is associated with considerable
      cumulative prolongation of AHR, which might help explain the role of atopy as a
      risk factor for asthma persistence.

PMID- 16083784
TI  - Dissecting asthma using focused transgenic modeling and functional genomics.
AB  - BACKGROUND: Asthma functional genomics studies are challenging because it is
      difficult to relate gene expression changes to specific disease mechanisms or
      pathophysiologic features. Use of simplified model systems might help to address
      this problem. One such model is the IL-13/Epi (IL-13-overexpressing transgenic
      mice with STAT6 expression limited to epithelial cells) focused transgenic mouse,
      which isolates the effects of a single mediator, IL-13, on a single cell type,
      the airway epithelial cell. These mice develop airway hyperreactivity and mucus
      overproduction but not airway inflammation. OBJECTIVE: To identify how effects of
      IL-13 on airway epithelial cells contribute to gene expression changes in murine
      asthma models and determine whether similar changes are seen in people with
      asthma. METHODS: We analyzed gene expression in ovalbumin allergic mice, IL-13
      overexpressing mice, and IL-13/Epi mice with microarrays. We analyzed the
      expression of human orthologues of genes identified in the mouse studies in
      airway epithelial cells from subjects with asthma and control subjects. RESULTS:
      In comparison with the other 2 models, IL-13/Epi mice had a remarkably small
      subset of gene expression changes. Human orthologues of some genes identified as
      increased in the mouse models were more highly expressed in airway epithelial
      cells from subjects with asthma than in controls. These included calcium
      activated chloride channel 1, 15-lipoxygenase, trefoil factor 2, and intelectin.
      CONCLUSION: The combination of focused transgenic models, DNA microarray
      analyses, and translational studies provides a powerful approach for analyzing
      the contributions of specific mediators and cell types and for focusing attention
      on a limited number of genes associated with specific pathophysiologic aspects of
      asthma.

PMID- 16083785
TI  - Endobronchial adenosine monophosphate challenge causes tachykinin release in the
      human airway.
AB  - BACKGROUND: Adenosine 5 monophosphate (AMP) has been shown to cause
      bronchoconstriction and a sensation of chest tightness when inhaled by asthmatic
      subjects. This response is attenuated after repeated inhalation of bradykinin,
      suggesting that AMP may act in part by the release of neuropeptides. OBJECTIVE:
      This study examined neuropeptide release in the human airway after endobronchial
      AMP challenge. METHODS: Endobronchial AMP challenge was performed in 20 subjects
      and tachykinin levels were measured after endobronchial AMP challenge and after
      placebo endobronchial challenge with saline. RESULTS: All subjects coughed
      immediately after adenosine challenge. There was a significant increase in
      neurokinin A and substance P levels (P < .01, P < .01 respectively) when post
      saline and post-AMP levels were compared. There was, however, no significant
      change in calcitonin gene related peptide levels (P = .37). CONCLUSION: This
      study demonstrates that endobronchial AMP challenge causes tachykinin release in
      the human airway in vivo.

PMID- 16083786
TI  - Rat tracheal epithelial responses to water avoidance stress.
AB  - BACKGROUND: Psychologic stress has major effects on many organs and cellular
      systems. The hypothalamic-pituitary-adrenal axis, corticotropin-releasing factor
      (CRF), mast cells, and nerves have all been shown to be involved in intestinal
      epithelial responses to stress. There has been little information in the
      literature on stress and the lung. OBJECTIVE: To investigate Wistar rat tracheal
      epithelial responses to acute water avoidance stress (1 hour). METHODS: Tracheal
      tissue was examined in Ussing chambers. RESULTS: Increases in short-circuit
      current, but not in conductance, occurred after stress and were inhibited by
      previous injection of the CRF 1 and 2 receptor antagonist, alpha-helical CRF-(9
      41). Electron microscopic morphologic evidence for tracheal mast cell activation
      and degranulation was found after stress. Stress and CRF injection both enhanced
      responses to substance P, but these effects were not inhibited by alpha-helical
      CRF. CONCLUSION: The data suggest that acute stress affects tracheal epithelium
      and sensitizes it to enhanced responses to substance P, partly through mast cell
      activation. Many but not all of these effects are mediated by CRF. These results
      offer the possibility that stress may be involved in inflammatory diseases of the
      lung such as asthma.

PMID- 16083787
TI  - Allergen-induced substance P synthesis in large-diameter sensory neurons
      innervating the lungs.
AB  - BACKGROUND: Tachykinins such as substance P are localized in unmyelinated slow
      conducting C fibers that can be activated by noxious stimuli and tissue
      inflammation. Substance P is seldom expressed in fast-conducting large-diameter
      (A-fiber) vagal sensory neurons. We have previously found that allergic
      inflammation causes a phenotypic change in tachykinergic innervation of the
      trachea such that the production of substance P is induced in large-diameter
      sensory neurons projecting mechanosensitive A fibers to the trachea. OBJECTIVE:
      To evaluate whether allergic inflammation also induces substance P synthesis in
      large-diameter sensory stretch-receptor neurons innervating guinea pig lungs, and
      to investigate potential mechanisms by which this may occur. METHODS: Sensitized
      guinea pigs were exposed to allergen (ovalbumin) aerosol. One day later,
      immunohistochemical analysis was performed on vagal sensory neurons that had been
      retrogradely labeled from the lungs. RESULTS: Ovalbumin inhalation caused a
      significant increase in substance P expression in large-diameter neurofilament
      positive nodose ganglion neurons that innervate the lungs (P < .05). This effect
      was decreased by ipsilateral vagotomy. Exposing isolated nodose ganglia to the
      sensitizing antigen, ovalbumin, also significantly increased substance P
      expression compared with control. CONCLUSION: Allergic inflammation induces
      substance P synthesis in large-diameter (A-fiber) nodose ganglion neurons
      innervating guinea pig lungs. This could contribute to the hyperreflexia seen in
      allergic airway disease. The full expression of this phenotypic switch in vagus
      nodose ganglion neurons requires intact vagus nerve, but if allergen reached the
      systemic circulation in sufficient quantities, it could also affect substance P
      synthesis by local activation of vagal ganglionic mast cells.

PMID- 16083788
TI  - Differential effects of (S)- and (R)-enantiomers of albuterol in a mouse asthma
      model.
AB  - BACKGROUND: (R)- and (S)-Enantiomers of albuterol likely exert differential
      effects in patients with asthma. The (R)-enantiomer binds to the beta2-adrenergic
      receptor with greater affinity than the (S)-enantiomer and is responsible for
      albuterol's bronchodilating activity. (S)-Albuterol augments bronchospasm and has
      proinflammatory actions. OBJECTIVE: The study aim was to determine whether the
      (S)-enantiomer, in contrast to the (R)-enantiomer, has adverse effects on
      allergic airway inflammation and hyperresponsiveness in a mouse asthma model.
      METHODS: Mice sensitized to ovalbumin (OVA) intraperitoneally on days 0 and 14
      were challenged with OVA intranasally on days 14, 25, and 35. On day 36, 24 hours
      after the final allergen challenge, the effect of the (R)- and (S)-enantiomers of
      albuterol (1 mg x kg(-1) x d(-1) administered by means of a miniosmotic pump from
      days 13-36) on airway inflammation and hyperreactivity was determined. RESULTS:
      In OVA-sensitized/OVA-challenged mice, (R)-albuterol significantly reduced the
      influx of eosinophils into the bronchoalveolar lavage fluid and airway tissue.
      (R)-Albuterol also significantly decreased airway goblet cell hyperplasia and
      mucus occlusion and levels of IL-4 in bronchoalveolar lavage fluid and OVA
      specific IgE in plasma. Although (S)-albuterol significantly reduced airway
      eosinophil infiltration, goblet cell hyperplasia, and mucus occlusion, it
      increased airway edema and responsiveness to methacholine in OVA-sensitized/OVA
      challenged mice. Allergen-induced airway edema and pulmonary mechanics were
      unaffected by (R)-albuterol. CONCLUSION: Both (R)- and (S)-enantiomers of
      albuterol reduce airway eosinophil trafficking and mucus hypersecretion in a
      mouse model of asthma. However, (S)-albuterol increases allergen-induced airway
      edema and hyperresponsiveness. These adverse effects of the (S)-enantiomer on
      lung function might limit the clinical efficacy of racemic albuterol.

PMID- 16083789
TI  - Allergen-specific nasal IgG antibodies induced by vaccination with genetically
      modified allergens are associated with reduced nasal allergen sensitivity.
AB  - BACKGROUND: We have performed a double-blind, placebo-controlled injection
      immunotherapy study with genetically modified derivatives of the major birch
      pollen allergen, Bet v 1 (Bet v 1-trimer, Bet v 1-fragments). OBJECTIVE: To
      investigate whether vaccination with genetically modified allergens induces
      allergen-specific antibodies in nasal secretions and to study whether these
      antibodies affect nasal allergen sensitivity. METHODS: A randomly picked subgroup
      of patients (n = 23; placebo, n = 10; trimer, n = 10; fragments, n = 3) was
      subjected to an extensive analysis of serum samples and nasal lavage fluids and
      to nasal provocation testing. Bet v 1-specific IgG(1-4) and IgA antibodies were
      determined in serum samples obtained before and after vaccination, after the
      birch pollen season, and 1 year after start of vaccination as well as in nasal
      lavage fluids obtained after the birch pollen season and 1 year after start of
      vaccination by ELISA. Nasal sensitivity to natural, birch pollen-derived Bet v 1
      was determined by active anterior rhinomanometry after the birch pollen season
      and 1 year after start of vaccination. RESULTS: Vaccination with genetically
      modified Bet v 1 derivatives, but not with placebo, induced Bet v 1-specific
      IgG1, IgG2, and IgG4, and low IgA antibodies in serum, which also appeared in
      nasal secretions, but no IgG3 antibodies. The levels of therapy-induced Bet v 1
      specific IgG4 antibodies in nasal secretions were significantly (P < .05)
      associated with reduced nasal sensitivity to natural, birch pollen-derived Bet v
      1 as objectively determined by controlled nasal provocation experiments.
      CONCLUSION: Our data demonstrate that vaccination with genetically modified
      allergens induces IgG antibody responses against the corresponding natural
      allergen not only in serum but also in mucosal fluids, where they may protect
      against allergen-induced inflammation.

PMID- 16083790
TI  - Levocetirizine: pharmacokinetics and pharmacodynamics in children age 6 to 11
      years.
AB  - BACKGROUND: The pharmacokinetics and pharmacodynamics of medications may differ
      between children and adults, necessitating different dose regimens for different
      age groups. Levocetirizine, the active enantiomer of cetirizine, is used in the
      treatment of allergic rhinitis and chronic urticaria in Europe. Its
      pharmacokinetics and pharmacodynamics have not yet been studied prospectively in
      school-age children. OBJECTIVES: This study was performed to investigate
      levocetirizine pharmacokinetic disposition and pharmacodynamics in relation to
      skin reactivity to histamine in children aged 6 to 11 years. METHODS: Blood
      samples were obtained at predose baseline and at defined intervals up to and
      including 28 hours after a 5-mg levocetirizine dose. Concurrently, epicutaneous
      tests with histamine phosphate, 1 mg/mL, were performed. Wheals and flares were
      traced at 10 minutes, and the areas were measured with a computerized digitizing
      system. RESULTS: In children aged 8.6 +/- 0.4 years (+/- SEM), the peak
      levocetirizine concentration was 450 +/- 37 ng/mL, and the time at which peak
      concentrations occurred was 1.2 +/- 0.2 hours. The terminal elimination half-life
      was 5.7 +/- 0.2 hours, the oral clearance was 0.82 +/- 0.05 mL/min/kg, and the
      volume of distribution was 0.4 +/- 0.02 L/kg. Compared with predose areas, the
      wheals and flares produced by histamine phosphate were significantly decreased
      from 1 to 28 hours, inclusive (P < .05). Mean maximum inhibition of wheals and
      flares occurred from 2 to 10 hours (97% +/- 1%) and from 2 to 24 hours (93% +/-
      1%), respectively. CONCLUSIONS: Levocetirizine had an onset of action within 1
      hour and provided significant peripheral antihistaminic activity for 28 hours
      after a single dose. Once-daily dosing may be optimal in children aged 6 to 11
      years, as it is in adults.

PMID- 16083791
TI  - Striking deposition of toxic eosinophil major basic protein in mucus:
      implications for chronic rhinosinusitis.
AB  - BACKGROUND: The mechanisms by which eosinophilic inflammation damages the
      epithelium and contributes to recurrent acute exacerbations in chronic
      rhinosinusitis (CRS) have not been fully elucidated. OBJECTIVE: We tested the
      hypotheses that eosinophils deposit toxic major basic protein (MBP) in the mucus
      and that MBP reaches concentrations able to damage the sinonasal epithelium.
      METHODS: Tissue specimens with mucus attached to the tissue were carefully
      collected from 22 patients with CRS and examined by using immunofluorescence
      staining for MBP. This immunofluorescence was digitally analyzed to determine the
      area covered by MBP and the intensity of the staining (estimating MBP
      concentration). Levels of MBP in extracts from nasal mucus were quantitated by
      means of RIA. RESULTS: Heterogeneous eosinophilia was evident within tissue and
      mucus specimens. All tissue specimens showed intact eosinophils, but diffuse
      extracellular MBP deposition, as a marker of eosinophil degranulation, was rare.
      In contrast, all mucus specimens showed diffuse MBP throughout and abundant
      diffuse extracellular MBP deposition within clusters of eosinophils. Digitized
      analyses of MBP immunofluorescence revealed increased area coverage (P < .0001)
      in mucus compared with that seen in tissue. Estimated concentrations of MBP
      within the clusters suggested toxic levels. MBP concentrations in mucus extract
      reached 11.7 microg/mL; MBP was not detectable in healthy control subjects.
      CONCLUSION: In patients with CRS, eosinophils form clusters in the mucus where
      they release MBP, which is diffusely deposited on the epithelium, a process not
      observed in the tissue. Estimated MBP levels far exceed those needed to damage
      epithelium from the luminal side and could predispose patients with CRS to
      secondary bacterial infections.

PMID- 16083792
TI  - Intranasal tolerance induction with polypeptides derived from 3 noncross-reactive
      major aeroallergens prevents allergic polysensitization in mice.
AB  - BACKGROUND: Specific immunotherapy is less effective in patients with multiple
      allergic sensitizations compared with monosensitized patients. OBJECTIVE: We
      therefore established a mouse model of polysensitization to the major birch and
      timothy grass pollen allergens to test whether allergic polysensitization can be
      prevented by multiple allergen application via the mucosal route. METHODS: Female
      BALB/c mice were immunized intraperitoneally with recombinant (r) Bet v 1, rPhl p
      1, and rPhl p 5. For intranasal tolerance induction, a mixture of the complete
      allergens was compared with allergen-derived immunodominant peptides applied
      either as a mixture or as a synthetic hybrid peptide composed of the T-cell
      epitopes of the 3 allergens. RESULTS: Intranasal application of the mixture of
      the complete allergen molecules did not prevent polysensitization to the same
      allergens. In contrast, pretreatment with a mixture of the immunodominant
      peptides or the hybrid peptide led to significantly reduced allergen-specific IgE
      responses in sera, IL-4 production in vitro, and suppressed airway inflammation.
      TGF-beta mRNA levels did not change, and IL-10 production was significantly
      suppressed after the pretreatment. The fact that the reduction of IL-10 was not
      abrogated after IL-10 receptor neutralization and that tolerance was not
      transferable with splenocytes indicates that the suppression of T(H)2 responses
      in polysensitized mice might not be mediated by immunosuppressive cytokines.
      CONCLUSION: Our study demonstrates that it is possible to suppress allergic
      immune responses simultaneously to several clinical important allergens. Thus,
      mucosal coapplication of selected peptides/hybrid peptides could be the basis of
      a mucosal polyvalent vaccine to prevent multiple sensitivities in atopic
      patients.

PMID- 16083793
TI  - Prevalences of positive skin test responses to 10 common allergens in the US
      population: results from the third National Health and Nutrition Examination
      Survey.
AB  - BACKGROUND: Allergy skin tests were administered in the second and third National
      Health and Nutrition Examination Surveys (NHANES II and III) conducted in the
      United States from 1976 through 1980 and 1988 through 1994, respectively.
      OBJECTIVES: This study estimated positive skin test response rates in NHANES III
      and identified predictors of one or more positive test responses. Comparisons
      with NHANES II were also made. METHODS: In NHANES III, 10 allergens and 2
      controls were tested in all subjects aged 6 to 19 years and a random half-sample
      of subjects aged 20 to 59 years. A wheal-based definition of a positive test
      response was used. RESULTS: In NHANES III, 54.3% of the population had positive
      test responses to 1 or more allergens. Prevalences were 27.5% for dust mite,
      26.9% for perennial rye, 26.2% for short ragweed, 26.1% for German cockroach,
      18.1% for Bermuda grass, 17.0% for cat, 15.2% for Russian thistle, 13.2% for
      white oak, 12.9% for Alternaria alternata, and 8.6% for peanut. Among those with
      positive test responses, the median number of positive responses was 3.0.
      Adjusted odds of a positive test response were higher for the following
      variables: age of 20 to 29 years, male sex, minority race, western region, old
      homes, and lower serum cotinine levels. For the 6 allergens common to NHANES II
      and III, prevalences were 2.1 to 5.5 times higher in NHANES III. CONCLUSIONS: The
      majority of the US population represented in NHANES III was sensitized to 1 or
      more allergens. Whether the higher prevalences observed in NHANES III reflect
      true changes in prevalence or methodological differences between the surveys
      cannot be determined with certainty.

PMID- 16083794
TI  - Airborne endotoxin in homes with domestic animals: implications for cat-specific
      tolerance.
AB  - BACKGROUND: Although endotoxin is known to increase symptoms in allergic
      individuals, early exposure might decrease sensitization. Similarly, the presence
      of an animal in the home has been associated with decreased sensitization to
      animal allergens. It has been suggested that the effect of animals could be
      explained by increased endotoxin exposure. OBJECTIVE: We sought to investigate
      the effects of domestic animals on airborne endotoxin. METHODS: By using a silent
      particle collector, air was sampled over 24 hours in homes with or without
      animals. The total volume sampled was approximately 1000 m3, which provides
      quantities of allergen and endotoxin that can easily be measured with standard
      assays. RESULTS: The quantity of endotoxin ranged from less than 0.5 to more than
      500 pg/m3, whereas cat and dog allergen ranged from less than 0.002 to more than
      5 ng/m3. Overall, the quantity of airborne endotoxin was not higher in homes with
      at least one animal. However, airborne endotoxin levels were significantly lower
      in homes with a cat compared with homes with a dog (P < .001). In keeping with
      this, there was a significant correlation between airborne Can f 1 and airborne
      endotoxin (r = 0.50, P < .01) but not between endotoxin and Fel d 1 (r = 0.17, P
      = .27). CONCLUSIONS: The results demonstrate that endotoxin is present in the air
      of almost all homes. Although higher levels were seen in homes with a dog,
      similar levels might be present in homes with no animals. The results argue that
      the effects of cat ownership cannot be explained by increased exposure to
      endotoxin.

PMID- 16083795
TI  - COX-2 inhibition enhances the TH2 immune response to epicutaneous sensitization.
AB  - BACKGROUND: Mechanical injury to the skin by scratching is an important feature
      of atopic dermatitis (AD). OBJECTIVE: To investigate the role of COX-2 in
      allergic skin inflammation elicited by epicutaneous (EC) sensitization via
      introduction of ovalbumin through shaved tape-stripped skin. METHODS: COX-2 mRNA
      was measured by quantitative PCR, and COX-2 protein was measured by Western
      blotting. We investigated the effect of administration of the COX-2 selective
      inhibitor NS-398 during EC sensitization with ovalbumin in a mouse model of AD
      characterized by eosinophil skin infiltration, elevated total and antigen
      specific IgE, and a systemic TH2 response to antigen. We further examined the
      response of COX-2-deficient mice to EC immunization with ovalbumin. RESULTS: Tape
      stripping caused a transient increase in skin COX-2 mRNA. In contrast, COX-2 mRNA
      was not increased after ovalbumin sensitization. Infiltration by eosinophils and
      expression of IL-4 mRNA in ovalbumin-sensitized skin sites, ovalbumin specific
      IgE and IgG1 antibody responses, and IL-4 secretion by splenocytes after
      ovalbumin stimulation were all significantly increased in EC mice that received
      NS-398. In contrast, ovalbumin specific IgG 2a antibody response and IFN-gamma
      secretion by splenocytes after ovalbumin stimulation were significantly decreased
      in these mice. COX-2-deficient mice also exhibited an enhanced systemic TH2
      response to EC sensitization. CONCLUSION: These results demonstrate that COX-2
      limits the TH2 response to EC sensitization and suggest that COX inhibitors may
      worsen allergic skin inflammation in patients with AD.

PMID- 16083796
TI  - Responsiveness to autologous sweat and serum in cholinergic urticaria classifies
      its clinical subtypes.
AB  - BACKGROUND: It has been reported that patients with cholinergic urticaria have a
      type 1 allergy to autologous sweat; however, the pathogenesis of that disorder
      has not been fully elucidated. OBJECTIVE: We investigated the responsiveness to
      autologous sweat and serum in patients with cholinergic urticaria in relation to
      their clinical characteristics. We further classified the clinical subtypes that
      are clearly characterized by responsiveness to in vivo and in vitro tests as well
      as their clinical features. METHODS: Intradermal tests with autologous sweat and
      serum were performed in 18 patients with cholinergic urticaria. Histamine release
      from peripheral blood basophils induced by autologous sweat was measured.
      RESULTS: Eleven of 17 patients with cholinergic urticaria showed positive
      reactions in skin tests with their own diluted sweat. Substantial amounts of
      sweat-induced histamine release from autologous basophils were observed in 10 of
      17 patients. Eight of 15 patients with cholinergic urticaria showed positive
      reactions in the autologous serum skin tests. All 6 patients who developed
      satellite wheals after the acetylcholine test showed hypersensitivity to sweat.
      Further, patients whose eruptions were coincident with hair follicles showed
      positive responses to the skin test with autologous serum, whereas patients whose
      eruptions were not coincident with hair follicles did not. CONCLUSION: On the
      basis of these findings, we propose that cholinergic urticaria should be
      classified into 2 distinct subtypes. The first (nonfollicular) subtype shows
      strong positive reactions to autologous sweat and negative reactions to
      autologous serum. The second (follicular) subtype shows weak reactions to
      autologous sweat and positive reactions to autologous serum.

PMID- 16083797
TI  - Lack of detectable allergenicity of transgenic maize and soya samples.
AB  - BACKGROUND: The safety issues regarding foods derived from genetically modified
      (GM) plants are central to their acceptance into the food supply. The potential
      allergenicity of proteins newly introduced in GM foods is a major safety concern.
      OBJECTIVE: We sought to monitor, in potentially sensitive human populations, the
      allergenicity effects of 5 GM materials obtained from sources with no allergenic
      potential and already under commercialization in the European Union. METHODS: We
      have performed skin prick tests with protein extracts prepared from transgenic
      maize (MON810, Bt11, T25, Bt176) and soya (Roundup Ready) samples and from
      nontransgenic control samples in 2 sensitive groups: children with food and
      inhalant allergy and individuals with asthma-rhinitis. We have also tested IgE
      immunoblot reactivity of sera from patients with food allergy to soya (Roundup
      Ready) and maize (MON810, Bt11, Bt176) samples, as well as to the pure transgenic
      proteins (CryIA[b] and CP4 5-enolpyruvylshikimate-3-phosphate synthase). RESULTS:
      None of the individuals undergoing tests reacted differentially to the transgenic
      and nontransgenic samples under study. None of the volunteers tested presented
      detectable IgE antibodies against pure transgenic proteins. CONCLUSION: The
      transgenic products under testing seem to be safe in terms of allergenic
      potential. We propose postmarket testing as an important screening strategy for
      putative allergic sensitization to proteins introduced in transgenic plants.

PMID- 16083798
TI  - Basic and clinical immunology.
AB  - The authors selected articles published in the literature from January 2004
      through December 2004 that were relevant to the areas of basic and clinical
      immunology. Several articles explored the development of TH1 or TH2 response and
      the role of the monocyte-T cell interaction. Others were articles describing the
      action of drugs commonly used in asthma to inhibit cytokine responses and the
      anti-inflammatory role of nonimmune pulmonary cells present in the lung. Several
      reports show how dendritic cells are being developed as vehicles for DNA vaccines
      aimed at stimulating cellular responses, an advance of great importance for HIV
      researchers working on vaccines, who are concerned about the different ways HIV
      evades the immune response. Other publications described Toll-like receptors in
      diverse cells, including mast cells and CD4+ T cells, for the recognition of
      viruses and bacteria. In the area of clinical immunology, an updated
      classification for primary immunodeficiencies with more than 100 identified genes
      responsible for these diseases and the report on the second clinical trial of
      gene therapy for X-linked severe combined immunodeficiency syndrome were
      published. Significant advances included the clinical prognosis in common
      variable immunodeficiency for patients presenting with lung pathology, the safety
      of live vaccines in partial DiGeorge syndrome, the report of patients with
      complete DiGeorge syndrome with the presence of peripheral blood T cells, the
      clinical spectrum of patients with NF-kappaB essential modifier (NEMO) gene
      deficiency, the publication of a consensus algorithm for the management of
      hereditary angioedema, and the report of immune restoration syndrome in pediatric
      HIV infection.

PMID- 16083799
TI  - The gastrointestinal tract is critical to the pathogenesis of acute HIV-1
      infection.
AB  - It has become evident that the gastrointestinal tract is preferentially and
      profoundly depleted of CD4+ T cells during acute HIV-1 infection. The enhanced
      susceptibility of gastrointestinal lymphoid tissue to HIV-1 is in part due to the
      large complement of CCR5+ memory CD4+ T cells resident at this site. Here we
      summarize the recent findings demonstrating that the gastrointestinal tract plays
      a critical role in the pathogenesis of acute HIV-1 and simian immunodeficiency
      virus infections. Ongoing work in this field is likely to have a significant
      effect on HIV research in the near future.

PMID- 16083800
TI  - Are you immunodeficient?

PMID- 16083801
TI  - From idiopathic infectious diseases to novel primary immunodeficiencies.
AB  - Primary immunodeficiencies are typically seen as rare monogenic conditions
      associated with detectable immunologic abnormalities, resulting in a broad
      susceptibility to multiple and recurrent infections caused by weakly pathogenic
      and more virulent microorganisms. By opposition to these conventional primary
      immunodeficiencies, we describe nonconventional primary immunodeficiencies as
      Mendelian conditions manifesting in otherwise healthy patients as a narrow
      susceptibility to infections, recurrent or otherwise, caused by weakly pathogenic
      or more virulent microbes. Conventional primary immunodeficiencies are suspected
      on the basis of a rare, striking, clinical phenotype and are defined on the basis
      of an overt immunologic phenotype, often leading to identification of the disease
      causing gene. Nonconventional primary immunodeficiencies are defined on the basis
      of a more common and less marked clinical phenotype, which remains isolated until
      molecular cloning of the causal gene reveals a hitherto undetected immunologic
      phenotype. Similar concepts can be applied to primary immunodeficiencies
      presenting other clinical features, such as allergy and autoimmunity.
      Nonconventional primary immunodeficiencies thus expand the clinical boundaries of
      this group of inherited disorders considerably, suggesting that Mendelian primary
      immunodeficiencies are more common in the general population than previously
      thought and might affect children with a single infectious, allergic, or
      autoimmune disease.

PMID- 16083802
TI  - Infant home endotoxin is associated with reduced allergen-stimulated lymphocyte
      proliferation and IL-13 production in childhood.
AB  - BACKGROUND: Infant endotoxin exposure has been proposed as a factor that might
      protect against allergy and the early childhood immune responses that increase
      the risk of IgE production to allergens. OBJECTIVE: Using a prospective study
      design, we tested the hypothesis that early-life endotoxin exposure is associated
      with allergen- and mitogen-induced cytokine production and proliferative
      responses of PBMCs isolated from infants with a parental history of physician
      diagnosed asthma or allergy. METHODS: We assessed household dust endotoxin at age
      2 to 3 months and PBMC proliferative and cytokine responses to cockroach allergen
      (Bla g 2), dust mite allergen (Der f 1), cat allergen (Fel d 1), and the
      nonspecific mitogen PHA at age 2 to 3 years. RESULTS: We found that increased
      endotoxin levels were associated with decreased IL-13 levels in response to
      cockroach, dust mite, and cat allergens, but not mitogen stimulation. Endotoxin
      levels were not correlated with allergen- or mitogen-induced IFN-gamma, TNF
      alpha, or IL-10. Increased endotoxin levels were associated with decreased
      lymphocyte proliferation after cockroach allergen stimulation. An inverse,
      although nonsignificant, association was also found between endotoxin and
      proliferation to the other tested stimuli. CONCLUSION: Increased early-life
      exposure to household endotoxin was associated with reduced allergen-induced
      production of the TH2 cytokine IL-13 and reduced lymphoproliferative responses at
      age 2 to 3 years in children at risk for allergy and asthma. Early-life endotoxin
      related reduction of IL-13 production might represent one pathway through which
      increased endotoxin decreases the risk of allergic disease and allergy in later
      childhood.

PMID- 16083803
TI  - Does early EBV infection protect against IgE sensitization?
AB  - BACKGROUND: There is indirect evidence that an increased infectious burden is
      associated with a decreased prevalence of IgE-mediated allergy during childhood.
      OBJECTIVE: To determine whether there is a relation between the serostatus of 13
      different viruses and parentally reported infections and IgE sensitization in 2
      year-old children. To investigate whether there is an interaction between
      cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to IgE
      sensitization. METHODS: A total of 246 infants were followed prospectively to 2
      years of age with clinical examinations, skin prick test, and specific IgE
      analyses and through analysis of seropositivity against adenovirus, influenza,
      parainfluenza, respiratory syncytial virus, CMV, EBV, herpes simplex virus, human
      herpesvirus 6, and varicella-zoster virus. RESULTS: There was some evidence that
      IgE sensitization (24%) tended to be more common among children who were
      seropositive against few compared with children who were seropositive against
      many viruses, but this was not statistically significant, and there was no
      consistent trend across the groups. IgE sensitization was statistically
      significantly less prevalent at 2 years of age among infants who were
      seropositive against EBV but not other viruses (adjusted odds ratio, 0.34; 95%
      CI, 0.14-0.86). The interaction of seropositivity against both CMV and EBV
      antibodies indicated a further reduction in the risk for IgE sensitization
      (adjusted odds ratio for interaction, 0.10; 95% CI, 0.01-0.92), indicating effect
      modification associated with seropositivity against CMV. CONCLUSION: Our results
      indicate that acquisition of EBV infection during the first 2 years of life is
      associated with a reduced risk of IgE sensitization, and this effect is enhanced
      by CMV coinfection.

PMID- 16083804
TI  - Biased use of VH5 IgE-positive B cells in the nasal mucosa in allergic rhinitis.
AB  - BACKGROUND: IgE antibody-producing B cells are enriched in the nasal mucosa in
      patients with allergic rhinitis because of local class switching to IgE. The
      expressed IgE VH genes also undergo somatic hypermutation in situ to generate
      clonal families. The antigenic driving force behind these events is unknown.
      OBJECTIVE: To examine the possible involvement of a superantigen in allergic
      rhinitis, we compared the variable (VH) gene use and patterns of somatic mutation
      in the expressed IgE heavy-chain genes in nasal biopsy specimens and blood from
      allergic patients and the IgA VH use in the same biopsy specimens and also those
      from nonallergic controls. METHODS: We extracted mRNA from the nasal biopsy
      specimens of 13 patients and 4 nonallergic control subjects and PBMCs from 7
      allergic patients. IgE and IgA VH regions were RT-PCR amplified, and the DNA
      sequences were compared with those of control subjects. We constructed a
      molecular model of VH5 to locate amino acids of interest. RESULTS: We observed a
      significantly increased frequency of IgE and IgA VH5 transcripts in the nasal
      mucosa of the allergic patients compared with the normal PBMC repertoire. Within
      IgE and IgA VH5 sequences in the nasal mucosa, the distribution of replacement
      amino acids was skewed toward the immunoglobulin framework regions. Three of 4
      nonintrinsic hotspots of mutation identified in the VH5 sequences were in
      framework region 1. The hotspots and a conserved VH5-specific framework residue
      form a tight cluster on the surface of VH5. CONCLUSION: Our results provide
      evidence for the activity of a superantigen in the nasal mucosa in patients with
      allergic rhinitis.

PMID- 16083805
TI  - Antibody responses against galactocerebroside are potential stage-specific
      biomarkers in multiple sclerosis.
AB  - BACKGROUND: Galactocerebroside, the major glycolipid of central nervous system
      myelin, is a known target for pathogenic demyelinating antibody responses in
      experimental allergic encephalomyelitis (EAE), the animal model of multiple
      sclerosis (MS). OBJECTIVE: To address the importance of anti-galactocerebroside
      (alpha-GalC) antibodies in MS and to evaluate them as biomarkers of disease.
      METHODS: alpha-GalC IgGs were quantified from sera of patients with MS and in
      marmoset EAE by a new immunosorbent assay. RESULTS: We report a significant
      difference in serum alpha-GalC IgG titers between patients with relapsing
      remitting (RR)-MS and healthy controls (HCs; P < .001). The frequencies of alpha
      GalC antibody-positive subjects (alpha-GalC titers > or = mean HC titers+3 SD)
      are also significantly elevated in RR-MS compared with HC (40% vs 0%; P = .0033).
      Immunoaffinity purified alpha-GalC IgGs from human serum bind to cultured human
      oligodendrocytes, indicating that the ELISA detects a biologically relevant
      epitope. Corroborating these findings, alpha-GalC antibody responses in marmoset
      EAE were similarly found to be specifically associated with the RR forms and not
      the peracute or progressive forms, in contrast with other anti-myelin antibodies
      (P = .0256). CONCLUSION: (1) alpha-GalC antibodies appear MS-specific and are not
      found in healthy subjects, unlike antibodies against myelin proteins; (2) when
      present, alpha-GalC antibodies identify mostly RR-MS and may be an indicator of
      ongoing disease activity. This novel assay is a suitable and valuable method to
      increase accuracy of diagnosis and disease staging in MS.

PMID- 16083806
TI  - Perilesional GM-CSF therapy of a chronic leg ulcer in a patient with common
      variable immunodeficiency.

PMID- 16083807
TI  - Asthma caused by cyanoacrylate used in a leisure activity.

PMID- 16083808
TI  - Cystic fibrosis gene mutations and chronic rhinosinusitis.

PMID- 16083809
TI  - Leukotriene receptor antagonists are not as effective as intranasal
      corticosteroids for managing nighttime symptoms of allergic rhinitis.

PMID- 16083810
TI  - Efficacy of ant venom immunotherapy and whole body extracts.

PMID- 16083812
TI  - Toll-like receptors and atopy.

PMID- 16083813
TI  - Chronic active Epstein-Barr virus infection of natural killer cells presenting as
      severe skin reaction to mosquito bites.

PMID- 16083815
TI  - Effects of storage in ozonised slurry ice on the sensory and microbial quality of
      sardine (Sardina pilchardus).
AB  - The use of slurry ice, both alone and in combination with ozone, as compared with
      traditional flake ice was investigated as a new refrigeration system for the
      storage of sardine (Sardina pilchardus). Microbiological, chemical and sensory
      analyses were carried out throughout a storage period of 22 days. According to
      sensory analyses, sardine specimens stored in ozonised slurry ice had a shelf
      life of 19 days, while counterpart batches stored in slurry ice or flake ice had
      shelf lives of 15 and 8 days, respectively. Storage in ozonised slurry ice led to
      significantly lower counts of aerobic mesophiles, psychrotrophic bacteria,
      anaerobes, coliforms, and both lipolytic and proteolytic microorganisms in
      sardine muscle, and of surface counts of mesophiles and psychrotrophic bacteria
      in sardine skin as compared with the slurry ice and the flake ice batches. In all
      cases, the slurry ice batch also exhibited significantly lower microbial counts,
      both in muscle and skin, than the flake ice batch. Chemical parameters revealed
      that the use of slurry ice slowed down the formation of TVB-N and TMA-N to a
      significant extent in comparison with storage in flake ice. A combination of
      slurry ice with ozone also allowed a better control of pH and TMA-N formation as
      compared with slurry ice alone. This work demonstrates that the combined use of
      slurry ice and ozone for the storage of sardine can be recommended to improve the
      quality and extend the shelf life of this fish species.

PMID- 16083816
TI  - Monitoring the bacterial population dynamics during fermentation of artisanal
      Argentinean sausages.
AB  - The dynamics of the microbial community responsible for the artisanal
      fermentation of dry sausage produced in Argentina was investigated by using
      classical and molecular approaches. The combined use of RAPD analysis with
      primers M13, XD9, RAPD1 and RAPD2 and 16S rDNA sequencing were applied to the
      identification and intraspecific differentiation of 100 strains of lactobacilli
      and Micrococcaceae. DGGE analysis was used to monitor the dynamic changes in
      population after total microbial DNA was directly extracted from sausages and
      subjected to PCR using V3f (GC), Bact-0124f-GC and Univ-0515r primers. The
      sequence analysis of 16S rDNA of the dominant species was also carried out.
      Lactobacillus sakei and Lactobacillus plantarum were the dominant lactic acid
      organisms during the fermentation while Staphylococcus saprophyticus represented
      the dominant species of Micrococcaceae. It was demonstrated that the ripening
      process of Argentinean artisanal fermented sausage is driven by a limited number
      of Lactobacillus and Staphylococcus strains selected from environmental
      microbiota by the ability to best compete under the prevailing conditions of the
      ecological niche. The identification of dominant communities present in this
      artisanal fermented sausage can help in the selection of starter cultures
      consisting in well adapted strains to the particular production technology.

PMID- 16083818
TI  - Risk factors for contamination of ready-to-eat street-vended poultry dishes in
      Dakar, Senegal.
AB  - Our objective was to investigate the Salmonella and Campylobacter contamination
      of traditional ready-to-eat street-vended poultry dishes and to assess the
      association of some restaurant characteristics and cooking practices with the
      contamination of these meals. One hundred and forty-eight street-restaurants were
      studied from January 2003 to April 2004 in Dakar. A questionnaire was submitted
      to the managers, and samples of ready-to-eat poultry dishes were taken.
      Salmonella spp. was isolated in 20.1% of the 148 street-restaurants studied and
      in 10.1% samples of poultry dishes. The most prevalent serovars isolated were
      Salmonella hadar, Salmonella enteritidis and Salmonella brancaster. Campylobacter
      jejuni was detected in only 3 restaurants and 3 poultry dishes. Not peeling and
      not cleaning vegetables and other ingredients during meal preparation (OR=3.58),
      dirty clothing for restaurant employees (OR=4.65), reheating previously cooked
      foods (OR=5.2), and no kitchen and utensils disinfection (OR=3.47) were
      associated with an increasing risk of Salmonella contamination. Adequate cooking
      procedures decreased the risk of Salmonella contamination (OR=0.15).

PMID- 16083817
TI  - Probiotic effects of Lactobacillus casei on DSS-induced ulcerative colitis in
      mice.
AB  - We tested the effect of Lactobacillus casei strain Shirota (LcS) on the murine
      model of ulcerative colitis induced by dextran sodium sulphate. The effect of LcS
      was tested either as a prophylactic 10 days before the onset of the disease,
      simultaneously with ulcerative colitis induction or continued 10 days after the
      disease was induced. LcS was not able to prevent the disease induction in any of
      the experiments. However, important clinical parameters including blood anemia
      indicators, body weight, and organ weight were improved in the animals receiving
      LcS as compared with the ulcerative colitis-induced controls. Increased colonic
      epithelial regeneration in the LcS treated animals was observed in the chronic
      stage. The results seemed better for the simultaneous short LcS treatment where
      some parameters remained similar to the PBS controls, including disease activity
      scores measured in the acute stage. We can conclude that although LcS alone
      cannot prevent the induction of ulcerative colitis by dextran sodium sulphate, it
      can improve the clinical condition of the mice. This could imply important
      biological consequences for the human situation. Further studies including LcS or
      other probiotic bacteria together with the available treatment are encouraged.

PMID- 16083819
TI  - Analysis of PCR-based methods for characterization of Listeria monocytogenes
      strains isolated from different sources.
AB  - Listeria monocytogenes strains, isolated from various sources (food, environment,
      and animals), were used to test different PCR-based methods to investigate their
      capability to define the strain origin. RAPD-PCR with three primers and the SAU
      PCR method, in which the DNA was first digested with the Sau3A restriction
      endonuclease and then amplified with a primer designed on the restriction site,
      were carried out, and the profiles obtained were used to perform cluster
      analysis. Based on the cluster analysis of Listeria spp. strains, obtained from
      international collections, the coefficient of similarity was selected. The
      results obtained showed that the methods tested in the study gave different
      levels of differentiation between the strains tested. The RAPD protocol using the
      P1254 primer and the SAU-PCR gave appreciable results only for strains isolated
      from animals and from a food processing plant in two different periods of the
      year 2003. Better differentiation was observed using the RAPD-PCR with primer
      D8635. As a matter of fact, it was able to distinguish L. monocytogenes obtained
      from different species of animals, different food samples and strains from the
      same production plant isolated in different periods of the year. Also primer M13
      gave positive results, but the coefficient of similarity to use had to be
      increased to 80%. On the basis of the results observed, RAPD-PCR with primers
      D8635 and M13 should be considered reliable tools for epidemiological
      investigations focusing on L. monocytogenes.

PMID- 16083820
TI  - Control of Listeria monocytogenes in model sausages by enterocin AS-48.
AB  - In this work we describe the control of Listeria monocytogenes CECT 4032 in
      sausage by adding the enterocin AS-48 producer strains Enterococcus faecalis A-48
      32 and Enterococcus faecium S-32-81, and also by adding a semi-purified
      preparation of the bacteriocin. Addition of preformed AS-48 caused a significant
      decrease (P<0.01) in the number of viable listeria even at the lowest bacteriocin
      concentration tested (112 AU/g). At a higher concentration (225 AU/g) listeria
      were below the detection level (1.99 log units/g) in meat at 3 days of incubation
      but growth of listeria was observed again after 9 days. For an AS-48
      concentration of 450 AU/g, no viable listeria were detected after 6 and 9 days of
      incubation. When E. faecalis A-48-32 was used as inoculum at approximately 10(7)
      cfu/g, listeria counts decreased progressively from start of experiment, being
      below detection level at day 9. The best results were obtained with E. faecium S
      32-81, since listeria were undetectable at 6 days of incubation. Bacteriocin
      concentrations in samples reached concentrations of 60 and 80 AU/g for strains A
      48-32 and S-32-81, respectively. These results clearly indicate that AS-48 can be
      used in the control of L. monocytogenes in sausages.

PMID- 16083821
TI  - Antimicrobial resistance profiles of dairy and clinical isolates and type strains
      of enterococci.
AB  - The susceptibility to 30 antimicrobial agents was determined by the disk
      diffusion method for a collection of 172 enterococcal strains, including 96
      isolates from dairy sources, 50 isolates of human and veterinary origin, and 26
      reference strains from 24 different enterococcal species. Results were analysed
      by hierarchic numerical methods to cluster strains and to group antimicrobials
      according to similarity profiles. Resistance to 17 of the 30 antimicrobials
      showed to be correlated, leading to four groups reflecting the mode of action:
      quinolones (ofloxacin, enrofloxacin, ciprofloxacin and norfloxacin); macrolides
      (erythromycin, spiramycin), phenicols (cloramphenicol) and tetracyclins
      (tetracycline, oxytetracyclin); aminoglycosides (gentamicin, kanamycin) and
      lincosamides (clindamycin); penicillins (amoxicillin, ampicillin, penicillin G,
      piperacillin) and carbapenems (imipenem). Overall, the genus Enterococcus behaved
      as resistant to lincomycin, colistin, polimixin B and, with a few exceptions in
      dairy isolates, to methicillin. In general, all isolates were susceptible to
      vancomycin, cloramphenicol and fusidic acid. Clusters containing only dairy
      isolates were susceptible to the majority of antimicrobials tested, as opposed to
      clusters constituted only by clinical enterococcal isolates. Among the clinical
      isolates, 62% were highly multiresistant. Low level gentamicin resistance was
      found to be associated with clinical enterococci. Among dairy isolates, those
      that clustered with clinical isolates were both resistant to gentamicin and
      identified as Enterococcus faecalis. Resistance to macrolides, quinolones,
      penicillins and imipenem was found to be associated also with clinical
      environments, mainly with multiresistant isolates, contrary to what is generally
      agreed as a characteristic of the genus. Veterinary clinical isolates were mainly
      grouped with the multiresistant clinical human isolates. The 26 reference
      enterococcal strains were distributed in clusters with different antibiotic
      resistance profiles and were mainly clustered with dairy isolates.

PMID- 16083822
TI  - Modelling inactivation of Listeria monocytogenes by pulsed electric fields in
      media of different pH.
AB  - A study of the effect of square-wave pulsed electric fields (PEF) on the
      inactivation of Listeria monocytogenes in McIlvaine buffer of different pH (3.5
      7.0) was conducted. L. monocytoges was more PEF sensitive at higher electric
      field strengths (E) and in media of low pH. A treatment at 28 kV/cm for 400 mus
      that inactivated 1.5, 2.3 and 3.0 Log10 cycles at pH 7.0, 6.5 and 5.0
      respectively destroyed almost 6.0 Log10 cycles at pH 3.5. The general shape of
      survival curves of L. monocytogenes PEF treated at different pH was
      convex/concave upwards. A mathematical model based on the Weibull distribution
      accurately described these survival curves. At each pH, the shape parameter (n
      value) did not depend on E. The relationship between n value of the Weibull model
      and the pH of the treatment medium was described by the Gompertz equation. A
      multiple linear regression model using three predictor variables (E, E2, pH2)
      related the Log10 of the scale paramenter (b value) of the Weibull model with E
      and pH of the treatment medium. A tertiary model developed using McIlvaine buffer
      as treatment medium predicted satisfactorily the inactivation of L. monocytogenes
      in apple juice.

PMID- 16083823
TI  - Foodborne protozoan parasites.
AB  - This report addresses Cryptosporidium, Giardia, Cyclospora, and more briefly,
      Toxoplasma as the main parasitic protozoa of concern to food production
      worldwide. Other parasitic protozoa may be spread in food or water but are not
      considered as great a risk to food manufacture. The protozoan parasites
      Cryptosporidium, Giardia, and Cyclospora have proven potential to cause
      waterborne and foodborne disease. Toxoplasma gondii has been considered a risk in
      specific cases, but humans are not its primary host. Cryptosporidium and Giardia
      are widespread in the environment, particularly the aquatic environment, and
      major outbreaks of cryptosporidiosis and giardiasis have occurred as a result of
      contaminated drinking water. Large outbreaks of waterborne cyclosporiasis have
      not been identified. Cryptosporidium, Giardia, and Cyclospora have potential
      significance in the preparation and consumption of fresh produce and in catering
      practice, in which ready-to-eat foods may be served that have not received heat
      treatment. None of the three organisms Cryptosporidium, Giardia, and Cyclospora
      has been shown to be a problem for heat processed food or tap water that has
      undergone appropriate treatment at a water treatment works. All three are
      sensitive to standard pasteurisation techniques. Although humans are not a
      primary host for T. gondii, the potential exists for both waterborne and
      foodborne toxoplasmosis. Parasitic protozoa do not multiply in foods, but they
      may survive in or on moist foods for months in cool, damp environments. Their
      ecology makes control of these parasites difficult. For general control of
      parasitic protozoa in the food chain, the following steps are necessary: - Follow
      good hygienic practice in food service and catering industries.- Minimise
      dissemination of cysts and oocysts in the farming environment and via human waste
      management.- Include these microorganisms in Hazard Analysis Critical Control
      Point (HACCP) plans of water suppliers, industries or sectors that use fresh
      produce, and operations in which contaminated process or ingredient water could
      end up in the product (e.g., where water supplies may become contaminated).

PMID- 16083825
TI  - Diagnosis and treatment of central nervous system involvement in non-Hodgkin's
      lymphoma.
AB  - The diagnosis of lymphoma of the central nervous system (CNS) has been
      facilitated by advances in neuroimaging and laboratory analysis of cerebrospinal
      fluid. The most common form of central nervous system CNS involvement in non
      Hodgkin's lymphoma (NHL) is leptomeningeal disease. After a diagnosis is
      established, the use of intrathecal or systemic chemotherapy and radiotherapy can
      improve survival and palliate symptoms. High-dose systemic chemotherapy with
      hematopoietic stem cell transplantation is an important treatment option at
      central nervous system relapse of NHL and for primary CNS lymphoma. The prognosis
      for disease-free survival and cure is better for patients who have treatment of
      CNS disease before transplantation than for patients who have active central
      nervous system disease at the time of transplant.

PMID- 16083826
TI  - Treatment of primary central nervous system lymphoma.
AB  - Primary central nervous system lymphoma (PCNSL) describes a malignant non
      Hodgkin's lymphoma (NHL) whose sole site of involvement is the central nervous
      system (CNS). The diagnosis of PCNSL must be differentiated from systemic NHL
      with metastasis to the CNS, which usually occurs late in the course of systemic
      disease. PCNSL accounts for approximately 4% to 7% of primary brain tumors, and
      its incidence has been increasing since the mid-1970s. Compared with other more
      common malignant primary brain tumors, PCNSL tends to be more amenable to
      radiotherapeutic and chemotherapeutic intervention. In this article, the authors
      review the standard treatment for upfront and recurrent PCNSL.

PMID- 16083827
TI  - Prognostic factors in primary central nervous system lymphomas.
AB  - Efforts to identify survival predictors in primary central nervous system
      lymphoma (PCNSL) have produced isolated, unconfirmed observations in small
      retrospective and prospective series. Age and performance status are two
      unanimously accepted prognostic factors. These and other independent predictors
      of survival were used by the International Extranodal Lymphoma Study Group
      (IELSG) to establish a prognostic scoring system able to distinguish risk groups
      in PCNSL. The IELSG score will improve further with better knowledge of these
      malignancies, especially with the inclusion of molecular and pharmacogenetic
      variables able to identify lymphomas with different chemosensitivities or degrees
      of aggressiveness. In the years ahead, a well-established prognostic score will
      allow the separation of patients into risk groups, which could result in the
      application of risk-tailored therapeutic strategies.

PMID- 16083828
TI  - Unusual variants of primary central nervous system lymphoma.
AB  - Rare variants of primary central nervous system lymphoma (PCNSL) include unusual
      sites of presentation (eg, neurolymphomatosis and primary leptomeningeal
      lymphoma) and uncommon pathologic entities. Neurolymphomatosis involves
      peripheral nerves and nerve roots in addition to systemic and central nervous
      system (CNS) sites. Diagnosis requires a high index of suspicion, and treatment
      incorporates the principles of therapy for systemic and CNS lymphoma. Primary
      leptomeningeal lymphoma can present with symptoms of raised intracranial pressure
      or cranial or spinal polyradiculopathies. Diagnosis can be made by examining
      cerebrospinal fluid and incorporating immunophenotyping and molecular pathology
      techniques. Treatment options include irradiation and intrathecal or systemic
      chemotherapy. The features of PCNSL of T-cell origin and indolent B-cell PCNSL
      also are discussed.

PMID- 16083829
TI  - AIDS-related primary central nervous system lymphoma.
AB  - Primary central nervous system lymphoma (PCNSL) can develop in the setting of
      profound immunosuppression, including late-stage infection with HIV. The
      management of such patients has yet to be defined optimally and differs
      substantially from that of immunocompetent patients who have PCNSL. The clinical
      features, diagnosis, and management of AIDS-related PCNSL are reviewed. The
      authors focus on commonly encountered diagnostic and therapeutic dilemmas and
      explore some promises and pitfalls of Epstein-Barr virus-directed therapies.

PMID- 16083830
TI  - Clinical features and diagnosis of primary central nervous system lymphoma.
AB  - This article reviews the clinical features of primary central nervous system
      lymphoma (PCNSL) in immunocompetent and immunocompromised patients. Clinical
      presentation, differential diagnosis, diagnostic testing, and staging evaluation
      in both immunocompetent and AIDS patients who have PCNSL are discussed. The
      differing role of biopsy in these two populations also is addressed.

PMID- 16083831
TI  - Pathology and genetics of primary central nervous system and intraocular
      lymphoma.
AB  - Ongoing studies based on gene expression profile analysis using microarrays have
      provided preliminary evidence for significant molecular distinctions between
      primary central nervous system lymphoma (PCNSL) and nodal lymphomas of the large
      B-cell type. The application of array-based comparative genomic hybridization
      techniques attempts to identify genomic distinctions between PCNSL and nodal
      lymphomas and to identify the molecular markers that relate to prognosis. It is
      possible that insights gained from these studies will facilitate the development
      of targeted therapies, which address the fundamental genetic mutations that drive
      PCNSL and intraocular lymphoma growth.

PMID- 16083832
TI  - New treatment approaches in primary central nervous system lymphoma.
AB  - A major advance in the treatment of primary central nervous system lymphoma
      (PCNSL) was made when the addition of chemotherapy to radiotherapy was shown to
      improve patient survival significantly. However, few chemotherapeutic agents are
      able to cross the blood-brain barrier. New therapeutic approaches in PCNSL are
      based on: the treatment of systemic non-Hodgkin's lymphomas with monoclonal
      antibodies and intensive chemotherapy followed by hematopoietic stem cell rescue,
      new chemotherapeutic agents with central nervous system penetration, or blood
      brain barrier disruption to enhance drug delivery to the brain. This article
      discusses the rationale and results of these innovative approaches.

PMID- 16083833
TI  - Treatment-related neurotoxicity.
AB  - Two challenges need to be addressed to improve the outcome of patients with
      primary central nervous system lymphoma. The first challenge is to develop
      therapies that result in less toxicity and improved long-term outcome. The second
      challenge is to develop interventions to help those patients who develop
      treatment-related neurotoxicity; ongoing collaborative efforts are required to
      improve communication and understanding of this complication. Long-term follow up
      of prospective therapeutic studies should report on both disease control and the
      development of neurotoxicity. New protocols should include prospective
      longitudinal measures of neurocognitive function.

PMID- 16083834
TI  - Diagnosis and management of primary intraocular lymphoma.
AB  - Primary intraocular lymphoma (PIOL) is a subset of primary central nervous system
      lymphoma. The incidence of PIOL has increased in the past 20 years. PIOL often
      presents as chronic uveitis that is resistant to corticosteroid therapy.
      Diagnosing PIOL can be challenging and requires an expert pathologist. The
      treatment of PIOL is difficult because of its high recurrence rate and refractory
      nature. The objective for the future is to improve diagnostic techniques and
      therapeutic success while minimizing ocular toxicities.

PMID- 16083835
TI  - Secondary central nervous system lymphoma: risk factors and prophylaxis.
AB  - Patients diagnosed with diffuse large-cell lymphoma, peripheral T-cell non
      Hodgkin's lymphoma or mantle cell lymphoma (either with a high serum lactate
      dehydrogenase level), more than one extranodal site, or who are a high risk
      according to the international Prognostic Index, should receive central nervous
      system prophylaxis either with intrathecal or high-dose systemic chemotherapy.
      The appropriateness of the same prophylaxis at relapse needs to be addressed in
      further studies.

PMID- 16083836
TI  - Leptospirosis among patients presenting with dengue-like illness in Puerto Rico.
AB  - Leptospirosis is difficult to distinguish from dengue fever without laboratory
      confirmation. Sporadic cases/clusters of leptospirosis occur in Puerto Rico, but
      surveillance is passive and laboratory confirmation is rare. We tested for
      leptospirosis using an IgM ELISA on sera testing negative for dengue virus IgM
      antibody and conducted a case-control study assessing risk factors for
      leptospirosis, comparing clinical/laboratory findings between leptospirosis (case
      patients) and dengue patients (controls). Among 730 dengue-negative sera, 36 (5%)
      were positive for leptospirosis. We performed post mortem testing for
      leptospirosis on 12 available specimens from suspected dengue-related fatalities;
      10 (83%) tested positive. Among these 10 fatal cases, pulmonary hemorrhage and
      renal failure were the most common causes of death. We enrolled 42 case-patients
      and 84 controls. Jaundice, elevated BUN, hyperbilirubinemia, anemia, and
      leukocytosis were associated with leptospirosis (p < .01 for all). Male sex,
      walking in puddles, rural habitation, and owning horses were independently
      associated with leptospirosis. Epidemiological, clinical, and laboratory criteria
      may help distinguish leptospirosis from dengue and identify patients who would
      benefit from early antibiotic treatment.

PMID- 16083837
TI  - Sensors based on double-decker rare earth phthalocyanines.
AB  - Phthalocyanines are interesting materials for sensing applications because their
      physicochemical properties are susceptible to be modified by the presence of
      certain molecules. Among the large family of the phthalocyanines, the sensing
      properties of double-decker phthalocyanines (which are sandwich-type complexes
      where a lanthanide metal is co-ordinated with two phthalocyanine rings) are of
      special interest due to their unique physicochemical properties. Their high
      intrinsic semiconductivity and their rich electrochemical and electrochromic
      behaviour, facilitate enormously the measurement of the changes in the
      physicochemical properties caused by the environment. In spite of their
      remarkable sensing behaviour, bisphthalocyanines have not been so extensively
      studied as sensitive materials as the parent monophthalocyanine compounds. This
      is due to the difficulty of the synthesis and purification processes, and to the
      fact that these compounds are not commercially available. In this paper, the
      sensing devices constructed using rare earth bisphthalocyanines are revised
      (including sensors foe electronic noses and electronic tongues) and their
      advantages discussed.

PMID- 16083838
TI  - Photoinduced phenomena in corona poled polar organic films.
AB  - Organic materials have received considerable attention because of their large
      dipole moments and optical nonlinearities. The optically induced switching of
      material properties is important for studying the optoelectronic effects
      including second harmonic generation. Organic materials for photonic applications
      contain chromophore dipole which consist of acceptor and donor groups bridged by
      a delocalized pi-electron system. Both theoretical and experimental data show a
      reversible highly dipolar photoinduced intra molecular charge transfer in betaine
      type molecules accompanied by change of the sign and the value of the dipole
      moment. The arrangement of polar molecules in films is studied both by atom force
      microscopy and surface potential measurements. To understand the photo response
      of these materials, their spectroscopic and electrical properties are studied.
      The morphology and photoinduced surface potential switching of the self-assembled
      monolayers and polymer films are investigated.

PMID- 16083839
TI  - External levator advancement vs Muller's muscle-conjunctival resection for
      correction of upper eyelid involutional ptosis.
AB  - PURPOSE: To compare external levator advancement and Muller's muscle-conjunctival
      resection (conjunctivomullerectomy, or CJM) for correction of upper eyelid
      involutional ptosis. DESIGN: Retrospective, nonrandomized, comparative
      interventional case series. METHODS: Review of medical records of 159 patients
      (272 surgical procedures) who underwent external levator advancement or CJM was
      performed. MAIN OUTCOME MEASURES: Functional and cosmetic outcome, marginal
      reflex distance one (MRD1), and surgical complications. RESULTS: A total of 159
      patients (51 men, 108 women, mean age 70 years) underwent 272 surgical procedures
      for upper eyelid ptosis; concurrent blepharoplasty was performed in 141 cases.
      MRD1 increased an average of 1.6 (+/-1.5) mm, from 0.8 mm (+/-1.2) preoperatively
      to 2.3 mm (+/-1.2) postoperatively (P < .001). Fifteen patients (5.5%) underwent
      reoperation for residual ptosis, nine (18%) in the external levator advancement
      group, two (3%) in the CJM group, three (8%) in the external plus blepharoplasty
      group, and one (1%) in the CJM plus blepharoplasty group (P < .001). Patients who
      underwent external levator advancement had significantly more severe ptosis
      preoperatively but attained similar eyelid position postoperatively as compared
      with CJM patients. Complications included overcorrection in four cases (1.4%),
      lagophthalmos of 1 mm in 10 (3.6%), and pyogenic granuloma in two (<1%).
      CONCLUSIONS: External levator advancement and CJM performed alone or with
      concurrent blepharoplasty are effective treatments for upper eyelid ptosis.
      Residual ptosis or postoperative eyelid retraction occurs in up to 20% of cases
      and can be addressed successfully with a second operation.

PMID- 16083840
TI  - Evaluation of the cosmetic significance of external dacryocystorhinostomy scars.
AB  - PURPOSE: To evaluate the significance of the surgical scar of external
      dacryocystorhinostomy (DCR) as assessed by the patients. DESIGN: Cross-sectional
      questionnaire-based study. METHODS: Two hundred ninety-seven external DCRs were
      performed in 263 patients at the private practices of consultants who were
      attached to the Sydney Eye Hospital. Structured questionnaires were sent to
      patients, and the responses were evaluated. Patients were asked to assess the
      visibility of the scar and the significance of the scar to them on a scale of 1
      (least) to 5 (greatest). RESULTS: The average age of patients was 67.9 +/- 16
      years, (72% female, 28% male). Ninety-six percent of the patients were caucasians
      of Australian/West European descent. Sixty-one of 296 scars (20.6%) were felt to
      be visible by patients; 31 scars (10.5%) were rated >1 on a scale of 1 to 5 and
      12 scars (4%) were rated >2. The average age of patients was highest for those
      patients with invisible scars, and the lowest average age was for those with
      scars that were rated >1. A significantly higher proportion of female patients
      complained of marked scarring (>1 on a scale of 1 to 5). A significantly higher
      proportion of patients who complained of discomfort during suture removal also
      complained of marked scarring. CONCLUSION: In view of the low percentage of
      patients who complained of marked scarring, scarring should not be the main
      ground for deciding the approach to DCR surgery, particularly in older patients.
      These results are valid for the population that was studied and may be different
      for different racial backgrounds.

PMID- 16083841
TI  - Intracameral Vigamox (moxifloxacin 0.5%) is non-toxic and effective in preventing
      endophthalmitis in a rabbit model.
AB  - PURPOSE: To determine whether Vigamox (moxifloxacin 0.5% ophthalmic solution) can
      be safely injected intracamerally to prevent Staphylococcus aureus
      endophthalmitis in a rabbit model. DESIGN: Animal study. METHODS: The safety and
      bactericidal-effectiveness of Vigamox were evaluated in three stages using 189
      New Zealand White rabbits. (Stage 1) The toxicity of two intravitreal doses of
      Vigamox (moxifloxacin 500, 250 microg) was compared with vancomycin (1 mg) and
      saline. (Stage 2) A reproducible rabbit model of Staphylococcus aureus
      endophthalmitis was established. (Stage 3) The bactericidal effect of
      intracameral Vigamox (moxifloxacin 500, 250, 125, 50 microg) was compared with
      vancomycin (1 mg) and saline. Intracameral antibiotic therapy commenced
      immediately after Staphylococcus aureus intravitreal challenge (5000 cfu).
      Toxicity was evaluated by masked clinical examination using a slit-lamp, an
      indirect ophthalmoscope, and corneal-ultrasound pachymetry. The clinical
      examination included the exterior eye, cornea, anterior chamber, vitreous, and
      retina. The presentations were graded on a severity scale of 0, 0.5, 1, 2, and 3.
      The bactericidal efficacy was determined using intracameral colony counts.
      RESULTS: In the toxicity studies without bacterial challenge, the clinical scores
      of rabbits injected intracamerally with Vigamox were statistically equivalent to
      rabbits given intracameral vancomycin or saline. In the efficacy studies, eyes
      treated intravitreally with Vigamox, at all doses, or vancomycin were negative
      for Staphylococcus aureus and nontreated controls remained culture-positive.
      CONCLUSIONS: Vigamox appears to be nontoxic for intracameral injection and
      effective in preventing experimental endophthalmitis in the rabbit model. Further
      studies will determine the clinical role of intracameral Vigamox for surgical
      prophylaxis and postoperative therapy.

PMID- 16083842
TI  - Nonmydriatic digital imaging alternative for annual retinal examination in
      persons with previously documented no or mild diabetic retinopathy.
AB  - PURPOSE: To prospectively evaluate the Joslin Vision Network (JVN) for follow-up
      annual retinal examination for level of diabetic retinopathy (DR). DESIGN:
      Prospective cohort study. METHODS: Fifty-two patients with no or mild
      nonproliferative DR (Early Treatment Diabetic Retinopathy Study [ETDRS] level <
      or = 35) and no diabetic macular edema (DME) at dilated retinal examination 11 or
      more months earlier were imaged. Patients then had dilated retinal examination
      and color 35-mm seven standard field stereoscopic photography (ETDRS photographs)
      and completed a satisfaction survey. Level of DR determined from JVN images,
      clinical examination, and ETDRS photographs was compared. RESULTS: Two (1.9%)
      eyes had JVN images ungradable for level of DR. In the 102 gradable eyes (98.1%),
      JVN diagnosis exactly matched clinical examination for level of DR in 82 eyes
      (77.9%) and was within one level of DR in all eyes (100%). Three eyes (2.9%) had
      JVN images ungradable for DME; one of these eyes had DME by clinical examination.
      JVN diagnosis matched clinical examination for DME in all eyes (101) gradable by
      JVN. Fifty patients (96.1%) reported JVN imaging improved their understanding of
      eye disease, 100% were satisfied with JVN, and forty-eight (92.3%) would consider
      replacing dilated examination by their eye doctor with JVN imaging. CONCLUSIONS:
      JVN digital imaging closely matched clinical examination for level of DR and DME,
      would have resulted in no patients receiving less stringent follow-up, and was
      well accepted by patients. JVN digital imaging may be a suitable alternative for
      annual dilated retinal examination for determining level of DR or DME and
      appropriate follow-up comprehensive ophthalmic examination.

PMID- 16083843
TI  - Differences in keratoconus as a function of gender.
AB  - PURPOSE: To characterize gender differences in the Collaborative Longitudinal
      Evaluation of Keratoconus (CLEK) Study. DESIGN: Observational, longitudinal
      study. METHODS: A total of 1209 subjects at 16 clinics. For eye-specific
      categorical variables, the number of eyes per subject with the characteristic was
      counted. For eye-specific continuous variables, the mean of both eyes was
      calculated. Multivariate linear (for continuous outcomes) and logistic (for
      categorical outcomes) regression models were created for each baseline
      characteristic with statistically significant (P < or = .05) differences between
      men and women. Age, race, education, and corneal curvature were covariates.
      RESULTS: The women were older, more likely to report a family history of
      keratoconus, more likely to be nonwhite, and less likely to complete college than
      men. Vogt's striae and monocular and binocular high-contrast entrance acuity were
      the only visual characteristics that varied between men and women in the
      multivariate model. Women were more likely than men to report ocular symptoms of
      dryness and complaints based upon a composite score of ocular symptoms. Women
      reported more hours per day of near work and were less likely to report the
      ability to wear contact lenses for enough hours to permit reading at home in the
      evening. Women reported more visits to their eye care practitioner during the
      previous 12 months. NEI-VFQ results revealed differences in self-reported
      difficulty with distance activities and driving. CONCLUSIONS: Gender differences
      exist in patient history, vision, and ocular symptoms in keratoconus patients.

PMID- 16083844
TI  - Prophylaxis for second eye involvement in leber hereditary optic neuropathy: an
      open-labeled, nonrandomized multicenter trial of topical brimonidine purite.
AB  - PURPOSE: To test a topical agent with purported antiapoptotic properties as
      prophylactic treatment after first eye involvement in Leber hereditary optic
      neuropathy (LHON), a maternally-inherited disorder characterized by bilateral,
      often sequential, visual loss. DESIGN: Open labeled, nonrandomized prospective
      pilot study. METHODS: Nine primary mutation molecularly confirmed LHON patients
      with one eye vision loss for less than 6 months and normal visual function in the
      fellow eye were treated with brimonidine purite 0.15% (Alphagan P) 4 times daily
      in the unaffected eye for up to 2 years. Visual acuity was the primary efficacy
      outcome. Secondary measures included changes on automated perimetry and
      quantification of the relative afferent pupillary defect. RESULTS: There were 8
      men and 1 woman enrolled, aged 13 to 54 years (mean 32 years), eight with the
      11778 mitochondrial DNA (mtDNA) mutation, and one with the 3460 mutation. Despite
      normal visual acuity at baseline in all patients, 7 patients had some minimal
      changes in the central visual field of the study eye. All patients had
      deterioration of vision in their second eye. In 1 of the 2 patients who had
      treatment initiated within 16 days after first eye involvement, good visual
      acuity was maintained in the study eye at 15 month followup, despite a mildly
      abnormal study eye baseline visual field. CONCLUSIONS: LHON may be a bilateral
      condition at onset more frequently than appreciated, with asymmetric severity at
      presentation. Topical brimonidine purite in this dosage was unsuccessful in
      preventing second eye involvement in recently monocularly-symptomatic LHON.

PMID- 16083845
TI  - Hereditary optic neuropathies: from the mitochondria to the optic nerve.
AB  - PURPOSE: To review our current knowledge of inherited optic neuropathies. DESIGN:
      Perspective. METHODS: Literature review. RESULTS: The hereditary optic
      neuropathies consist of a group of disorders in which optic nerve dysfunction
      figures solely or prominently and direct inheritance is clinically or genetically
      proven. The most common of these disorders are autosomal dominant optic atrophy
      (Kjers' disease) and maternally-inherited Leber's hereditary optic neuropathy.
      Other inherited neurologic and systemic syndromic diseases will frequently
      manifest optic neuropathy. A selective vulnerability of the optic nerve to
      perturbations in mitochondrial function may underlie a final common pathway among
      these disorders. CONCLUSIONS: The ophthalmologist should be familiar with the
      clinical characteristics and diagnosis of the hereditary optic neuropathies.
      Recent advances in our understanding of the underlying pathophysiology of the
      inherited optic neuropathies may provide insight into their treatment and the
      treatment of acquired optic nerve disorders.

PMID- 16083847
TI  - A competition assay of magnesium affinity for EF-hand proteins based on the
      fluorescent indicator magnesium green.

PMID- 16083846
TI  - Evaluation of alpha-cyano ethers as fluorescent substrates for assay of
      cytochrome P450 enzyme activity.
AB  - We have previously reported the synthesis of four alpha-cyano-containing ethers
      based on 2-naphthaldehyde (2-NA) as cytochrome P450 (P450) fluorescent
      substrates. Activity detection was based on the formation of fluorescent 2-NA
      following substrate hydrolysis. A major limitation of these substrates was the
      need to remove NADPH, a required cofactor for P450 oxidation, before measuring 2
      NA fluorescence. In this article, we report the synthesis of a new series of
      novel P450 substrates using 6-dimethylamino-2-naphthaldehyde (6-DMANA), which has
      a green fluorescent emission that is well separated from the NADPH spectrum. A
      major advantage of the 6-DMANA substrates is that NADPH removal is not required
      before fluorescence detection. We used eight alpha-cyano ether-based substrates
      to determine the O-dealkylation activity of human, mouse, and rat liver
      microsomes. In addition, substrate activities were compared with the commercial
      substrate 7-ethoxyresorufin (7-ER). The catalytic turnover rates of both the 6
      DMANA- and 2-NA-based substrates were in some cases threefold faster than the
      catalytic turnover rate of 7-ER. The 2-NA-based substrates had greater turnover
      than did the 6-DMANA-based substrates. Murine and rat liver microsomes prepared
      from animals that had been treated with various P450 inducers were used to
      examine for isozyme-selective turnover of the substrates. The vastly improved
      optical properties and synthetic flexibility of the alpha-cyano ether compounds
      suggest that they are possibly good general P450 substrates.

PMID- 16083848
TI  - [Jejunal perforation by a fish bone diagnosed by CT-Scan: report of two cases].
AB  - The authors relate two cases of peritonitis secondary to jejunal perforation by a
      fish bone. Clinically, the first patient presented signs and symptoms of acute
      diverticulitis and the second had signs of duodenal perforation. In both cases,
      the diagnosis was made by the CT-scan revealing a linear radio-opaque object
      suggestive of a fish bone perforating the jejunum. At laparotomy of the first
      case, we found a perforation located above several loops of small bowel densely
      adhered to the nonabsorbable intra-abdominal mesh. Removal of the fish bone,
      suture of the jejunal perforation, washing and drainage of the abdominal cavity
      were performed. The mesh was removed and replaced by a polyglycolic acid mesh. In
      the second case, jejunal perforation occurred in an unaltered small bowel loop
      and a short intestinal resection was performed. The postoperative course was
      uneventful for both patients. These clinical cases allow us to discuss the
      several fish bone perforation site and our patients precipitating factors.

PMID- 16083849
TI  - Purification and properties of cobalamin-independent methionine synthase from
      Candida albicans and Saccharomyces cerevisiae.
AB  - In this study, we investigated methionine synthase from Candida albicans (CaMET
      6p) and Saccharomyces cerevisiae (ScMET 6p). We describe the cloning of CaMet 6
      and ScMet 6, and the expression of both the enzymes in S. cerevisiae. CaMET 6p is
      able to complement the disruption of met 6 in S. cerevisiae. Following the
      purification of ScMET 6p and CaMET 6p, kinetic assays were performed to determine
      substrate specificity. The Michaelis constants for ScMET 6p with CH(3)
      H(4)PteGlu(2), CH(3)-H(4)PteGlu(3), CH(3)-H(4)PteGlu(4), and l-homocysteine are
      108, 84, 95, and 13 microM, respectively. The Michaelis constants for CaMET 6p
      with CH(3)-H(4)PteGlu(2), CH(3)-H(4)PteGlu(3), CH(3)-H(4)PteGlu(4), and l
      homocysteine are 113, 129, 120, and 14 microM, respectively. Neither enzyme
      showed activity with CH(3)-H(4)PteGlu(1) as a substrate. We conclude that ScMET
      6p and CaMET 6p require a minimum of two glutamates on the methyltetrahydrofolate
      substrate, similar to the bacterial metE homologs. The cloning, purification, and
      characterization of these enzymes lay the groundwork for inhibitor-design studies
      on the cobalamin-independent fungal methionine synthases.

PMID- 16083850
TI  - Role of the snake venom toxin jararhagin in proinflammatory pathogenesis: in
      vitro and in vivo gene expression analysis of the effects of the toxin.
AB  - To assess the indirect effects of snake venom metalloproteinases (SVMP) on host
      tissue local necrosis, we investigated the effect of the SVMP jararhagin on the
      gene expression profiles of human fibroblasts in vitro and mouse tissue in vivo.
      Two functional classes of up-regulated proteins, cell death and inflammatory
      disease were identified as being significantly populated. The changes in gene
      expression observed by qRT-PCR on laser microdissected mouse muscle tissue
      treated with jararhagin were similar with significant up-regulation of
      proinflammatory transcripts such as IL-1 beta, IL-6, CXCL1, CXCL2, IL-8, and
      apoptosis, inflammation responsive transcripts such as TNF-alpha induced protein
      6. Proteolytically inactive jararhagin had no effect on the gene expression
      profile of fibroblasts, indicating proteolysis as the primary mechanism affecting
      gene expression of cells and tissues resulting in a proinflammatory, pro
      apoptotic host response which likely exacerbates the local necrosis frequently
      observed at the site of envenoming.

PMID- 16083851
TI  - The apoptosis inhibitory domain of FE65-like protein 1 regulates both apoptotic
      and caspase-independent programmed cell death mediated by tumor necrosis factor.
AB  - Tumor necrosis factor (TNF) can induce caspase-dependent (apoptotic) and caspase
      independent pathways to programmed cell death (PCD). Here, we demonstrate that
      stable transfection of a cDNA encompassing the C-terminal apoptosis inhibitory
      domain (AID) of FE65-like protein 1 into mouse L929 fibrosarcoma cells protects
      from caspase-independent as well as from apoptotic PCD induced by TNF. We show
      that the AID does not protect from caspase-independent PCD elicited by 1-methyl-3
      nitro-1-nitrosoguanidine, suggesting that the AID might prevent cell death by
      affecting assembly of the death inducing signaling complex of the 55 kDa TNF
      receptor or clustering of the receptor itself. Interference with caspase
      independent PCD mediated by the sphingolipid ceramide further increases
      protection conferred by the AID, as does the antioxidant butylated
      hydroxyanisole, implicating ceramide and reactive oxygen species as potential
      factors interacting with caspase-independent PCD regulated by the AID.

PMID- 16083852
TI  - Prolonged unbalanced growth induces cellular senescence markers linked with
      mechano transduction in normal and tumor cells.
AB  - Cellular senescence is induced by diverse means and hence thought to be mediated
      by multiple pathways. We show that prolonged unbalanced growth due to retardation
      of DNA replication elicits a senescence-like phenomenon irrespective of the cell
      type. In fact, modest inhibition of DNA replication by various means led to cell
      swelling, cytoskeletal alterations, and irregularly enlarged, flat cell shape.
      Such cells upregulated senescence-associated genes, and eventually lost division
      potential. These phenotypes, which define cellular senescence, were virtually
      reversed by reducing protein synthesis or blocking ERK of the MAP kinase family.
      These results suggest that cellular senescence is a manifestation of prolonged
      unbalanced growth linked with mechano transduction and can be prevented by at
      least two different ways.

PMID- 16083853
TI  - Cytoplasmic tethering of a RING protein RBCK1 by its splice variant lacking the
      RING domain.
AB  - RBCC protein interacting with PKC 1 (RBCK1) is a transcription factor belonging
      to the RING-IBR protein family and has been shown to shuttle between the nucleus
      and cytoplasm, possessing both the nuclear export and localization signals within
      its amino acid sequence. RBCK2, lacking the C-terminal half of RBCK1 including
      the RING-IBR domain, has also been identified as an alternative splice variant of
      RBCK1. RBCK2 shows no transcriptional activity and instead it represses the
      transcriptional activity of RBCK1. Here, we show that RBCK2 is present usually in
      the cytoplasm containing two Leu-rich regions that presumably serve as a nuclear
      export signal (NES). Moreover, an NES-disrupted RBCK1 that is mostly localized
      within the nucleus is translocated to the cytoplasm when coexpressed with RBCK2,
      suggesting that RBCK2 serves as a cytoplasmic tethering protein for RBCK1. We
      propose a novel and general function of RING-lacking splice variants of RING
      proteins to control the intracellular localization and functions of the parental
      RING proteins by forming a hetero-oligomeric complex.

PMID- 16083854
TI  - Chemical stress sensitive luminescent human cells: molecular biology approach
      using inducible Drosophila melanogaster hsp22 promoter.
AB  - A whole-cell bioassay has been developed for the total toxicity testing of liquid
      samples. The method is based on the induction of the bioluminescent activity of
      genetically manipulated mammalian cells. For that purpose, transfection was used
      to introduce, in HeLa cells, a DNA sensing element that responds to chemical
      stress agents (heavy metals, genotoxic agents, and endocrine-disrupting
      chemicals). Such element was designed to direct the expression of a reporting
      gene (firefly luciferase) through the activation of Drosophila melanogaster hsp22
      promoter. A molecular approach was conducted to optimize hsp22 promoter element
      in order to decrease the background expression level of the reporting gene and to
      increase the sensitivity of the bioassay for testing endocrine disruptors. As a
      result, in the presence of 20-100 microM cadmium chloride, a 6-fold increase in
      luciferase expression was obtained using a specially designed truncated hsp22
      promoter construction. The following chemicals known to be found in the polluted
      samples were tested: CdCl2, Cd(NO3)2, NaAsO2, alachlore, fentine acetate, thiram,
      and maneb. The stressing effect of each of them was sensitively detected by the
      present bioassay in the 0.05-50 microM concentration range.

PMID- 16083855
TI  - Microarray analysis of the genes induced by tetracycline-regulated expression of
      NDRF/NeuroD2 in P19 cells.
AB  - NeuroD-related factor (NDRF)/NeuroD2 is a basic helix-loop-helix (bHLH) protein
      that plays important roles in neuronal development. To elucidate the NDRF
      transcription network, we used mouse cDNA microarray analysis combined with a
      tetracycline-regulatable expression system in P19 embryonal carcinoma cells. Five
      genes were identified to be up-regulated in the presence of NDRF protein. RNA
      hybridization analysis confirmed that brain-lipid-binding protein (BLBP) and
      inhibitor of differentiation 1 (Id1) genes were among the five genes that were
      rapidly and significantly up-regulated after induction of NDRF. When a dominant
      negative form of NDRF protein was expressed during retinoic acid-induced neuronal
      differentiation of P19 cells, the BLBP gene, but not the Id1 gene, was potently
      repressed. Immunohistochemical analysis revealed that both NDRF and Id1
      immunoreactivities were observed in some granule cells of the cerebellum in the
      postnatal period. These results suggest that NDRF or its related bHLH proteins
      may act upstream of these genes in a subset of developing neurons.

PMID- 16083856
TI  - The hematopoietic transcription factor PU.1 regulates RANK gene expression in
      myeloid progenitors.
AB  - Osteoclasts are bone resorbing cells of hematopoietic origin. The hematopoietic
      transcription factor PU.1 is critical for osteoclastogenesis; however, the
      molecular mechanisms of PU.1-regulated osteoclastogenesis have not been explored.
      Here, we present evidence that the receptor activator of nuclear factor kappaB
      (RANK) gene that has been shown to be crucial for osteoclastogenesis is a
      transcriptional target of PU.1. The PU.1-/- progenitor cells failed to express
      the RANK gene and reconstitution of PU.1 in these cells induced RANK expression.
      Treatment of the PU.1 reconstituted cells with M-CSF and RANKL further augmented
      the RANK gene expression. To explore the regulatory mechanism of the RANK gene
      expression by PU.1, we have cloned the human RANK promoter. Transient
      transfection assays have revealed that the 2.2-kb RANK promoter was functional in
      a monocyte line RAW264.7, whereas co-transfection of PU.1 transactivated the RANK
      promoter in HeLa cells. Taken together, these results suggest that PU.1 regulates
      the RANK gene transcription and this may represent one of the key roles of PU.1
      in osteoclast differentiation.

PMID- 16083857
TI  - Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and
      3'-phosphoadenosine 5'-phosphate.
AB  - The human sulfotransferase, SULT1A3, catalyzes specifically the sulfonation of
      monoamines such as dopamine, epinephrine, and norepinephrine. SULT1A3 also has a
      unique 3,4-dihydroxyphenylalanine (Dopa)/tyrosine-sulfating activity that is
      preferentially toward their D-form enantiomers and can be stimulated dramatically
      by Mn2+. To further our understanding of the molecular basis for the unique
      substrate specificity of this enzyme, we solved the crystal structure of human
      SULT1A3, complexed with dopamine and 3'-phosphoadenosine 5'-phosphate, at 2.6 A
      resolution and carried out autodocking analysis with D-Dopa. The structure of
      SULT1A3 enzyme-ligand complex clearly showed that residue Glu146 can form
      electrostatic interaction with dopamine and may play a pivotal role in the
      stereoselectivity and sulfating activity. On the other hand, residue Asp86
      appeared to be critical to the Mn2+-stimulation of the Dopa/tyrosine-sulfating
      activity of SULT1A3, in addition to a supporting role in the stereoselectivity
      and sulfating activity.

PMID- 16083858
TI  - HRS inhibits EGF receptor signaling in the RT4 rat schwannoma cell line.
AB  - Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) is required
      for trafficking of cell surface receptors to the lysosome. Previously, we
      identified HRS as a protein that interacts with the neurofibromatosis 2 tumor
      suppressor schwannomin. In the present study, we established modified RT4
      schwannoma cell lines that inducibly express HRS and constitutively express
      epidermal growth factor receptor (EGFR) fused to the green fluorescent protein.
      We demonstrated that HRS expression reduced EGFR abundance and EGF-mediated Stat3
      activation. HRS expression also targeted EGFR to late endosomes. Schwannomin
      inhibited EGF-mediated Stat3 activation, consistent with HRS and schwannomin
      interacting in the same signaling pathway. Paradoxically, past studies have shown
      that HRS overexpression blocked EGFR trafficking to the late endosome and EGFR
      downregulation contrary to predictions of HRS function in HRS knockout studies.
      This study is the first to show that HRS can reduce the abundance of total and
      active EGFR and may reflect cell type-specific HRS function.

PMID- 16083859
TI  - Expression of HSG is essential for mouse blastocyst formation.
AB  - It has been shown recently that hyperplasia suppressor gene (HSG) is a powerful
      regulator for cell proliferation and has a critical role in mitochondrial fusion
      in many cells. However, little is known about its expression, localization, and
      function during oocyte maturation and early embryogenesis. In this study, with
      indirect immunofluorescent staining and Western blotting, we found that HSG was
      expressed in mouse oocytes and preimplantation embryos which primarily exhibited
      a submembrane distribution pattern in the cytoplasm. Moreover, HSG mainly
      associated with beta-tubulin during oocyte maturation and early embryonic
      development. When mouse zygotes were injected with HSG antisense plasmid and
      cultured in vitro, their capacity to form blastocysts was severely impaired. Our
      results indicate that HSG plays an essential role in mouse preimplantation
      development.

PMID- 16083860
TI  - Dissecting phenotypic variation among AIS patients.
AB  - We have created genital skin fibroblast cell lines directly from three patients
      in a Chinese family affected by androgen insensitivity syndrome (AIS). All
      patients in the family share an identical AR Arg840Cys mutant but show different
      disease phenotypes. By using the cell lines, we find that the mutation has not
      influenced a normal androgen-binding capacity at 37 degrees C but has reduced the
      affinity for androgens and may cause thermolability of the androgen-receptor
      complex. The impaired nuclear trafficking of the androgen receptor in the cell
      lines is highly correlated with the severity of donors' disease phenotype. The
      transactivity of the mutant is substantially weakened and the extent of the
      reduced transactivity reflects severity of the donors' disease symptom. Our data
      reveal that although etiology of AIS is monogenic and the mutant may alter the
      major biological functions of its wild allele, the function of the mutant AR can
      also be influenced by the different genetic backgrounds and thus explains the
      divergent disease phenotypes.

PMID- 16083861
TI  - Secondary structure probing of the human RNase MRP RNA reveals the potential for
      MRP RNA subsets.
AB  - RNase MRP is a ribonucleoprotein endoribonuclease involved in eukaryotic pre-rRNA
      processing. The enzyme possesses an RNA subunit, structurally related to that of
      RNase P RNA, that is thought to be catalytic. RNase MRP RNA sequences from
      Saccharomycetaceae species are structurally well defined through detailed
      phylogenetic and structural analysis. In contrast, higher eukaryote MRP RNA
      structure models are based on comparative sequence analysis of only five
      sequences and limited probing data. Detailed structural analysis of the Homo
      sapiens MRP RNA, entailing enzymatic and chemical probing, is reported. The data
      are consistent with the phylogenetic secondary structure model and demonstrate
      unequivocally that higher eukaryote MRP RNA structure differs significantly from
      that reported for Saccharomycetaceae species. Neither model can account for all
      of the known MRP RNAs and we thus propose the evolution of at least two subsets
      of RNase MRP secondary structure, differing predominantly in the predicted
      specificity domain.

PMID- 16083862
TI  - Cloning and expression of ligand-gated ion-channel receptor L2 in central nervous
      system.
AB  - An orphan receptor of ligand-gated ion-channel type (L2, also termed ZAC
      according to the presence of zinc ion for channel activation) was identified by
      computer-assisted search programs on human genome database. The L2 protein shares
      partial homology with serotonin receptors 5HT3A and 5HT3B. We have cloned L2 cDNA
      derived from human caudate nucleus and characterized the exon-intron structure as
      follows: (1) The L2 protein has four transmembrane regions (M1-M4) and a long
      cytoplasmic loop between M3 and M4. (2) The sequence is conserved in species
      including chimpanzee, dog, cow, and opossum. (3) Nine exons form its protein
      coding region and especially exon 5 corresponds to a disulfide bond region on the
      amino-terminal side. Our analysis using multiple tissue cDNA panels revealed that
      at least two splicing variants of L2 mRNA are present. The cDNA PCR amplification
      study revealed that L2 mRNA is expressed in tissues including brain, pancreas,
      liver, lung, heart, kidney, and skeletal muscle while 5HT3A mRNA could be
      detected in brain, heart, placenta, lung, kidney, pancreas, and skeletal muscle,
      and 5HT3B mRNA in brain, kidney, and skeletal muscle, suggesting different
      significance in tissue expression of these receptors. Regional expression of L2
      mRNA and protein was examined in brain. The RT-PCR studies confirmed L2 mRNA
      expression in hippocampus, striatum, amygdala, and thalamus in adult brain. The
      L2 protein was immunolocalized by using antipeptide antibodies. Immunostained
      tissue sections revealed that L2-like immunoreactivity was dominantly expressed
      in the hippocampal CA3 pyramidal cells and in the polymorphic layer of the
      dentate gyrus. We analyzed the expression of L2 protein in HEK293 cells using GFP
      fusion protein reporter system. Western blots revealed that L2 protein confers
      sugar chains on the extracellular side. In transfected HEK293 cells, cellular
      membranes and intracellular puncta were densely labeled with GFP, suggesting
      selective dispatch to the final destination.

PMID- 16083863
TI  - Bcl-2 mediated inhibition of erucylphosphocholine-induced apoptosis depends on
      its subcellular localisation.
AB  - The synthetic phospholipid derivative erucylphosphocholine (ErPC) is a potent
      inducer of apoptosis in human tumor cell lines. This membrane-targeted drug
      induces apoptosis independently from death receptor signaling through a
      mitochondrial pathway that is inhibited by over-expression of Bcl-2. Within the
      cell, Bcl-2 resides in membranes of mitochondria, endoplasmic reticulum (ER) and
      the nucleus. However, the importance of its subcellular localisation in distinct
      organelles for protection against apoptosis is not completely understood. To
      investigate the impact of Bcl-2 localised at defined subcellular compartments on
      its protective effects against ErPC-induced apoptosis, Bcl-2 expression was
      directed to the outer membrane of the mitochondria or the ER of Jurkat T Lymphoma
      cells, using Bcl-2 mutants with modified membrane anchors. The mitochondrial
      insertion sequence of ActA directed Bcl-2 to the mitochondria (Bcl-2/MT), the ER
      specific sequence of cytochrome b5 to the ER (Bcl-2/ER). Additionally, Jurkat
      cells expressing wild-type Bcl-2 (Bcl-2/WT) or a transmembrane domain-lacking
      mutant (Bcl-2/DeltaTM) were employed. While restricted expression of Bcl-2 either
      at membranes of the mitochondria or the ER strongly interfered with ErPC-induced
      mitochondrial damage and apoptosis, cytosolic Bcl-2/DeltaTM exhibited only
      reduced protection. Thus, membrane localisation of Bcl-2 is a prerequisite for
      substantial protection against ErPC-induced apoptosis. For efficient long-term
      inhibition of ErPC-induced apoptosis Bcl-2 had to be present in the membranes of
      both compartments, the ER and the mitochondria. The finding that ER-targeted Bcl
      2 interferes with ErPC-induced mitochondrial damage points to an involvement of
      the ER in apoptosis signaling upstream of the mitochondria and to a crosstalk
      between both compartments.

PMID- 16083864
TI  - Spinal cord injury triggers sensitization of wide dynamic range dorsal horn
      neurons in segments rostral to the injury.
AB  - A spinal cord injury (SCI) was produced in adult rats by complete spinal cord
      transection at L6-S1. Neuropathic pain behaviors similar to the chronic central
      pain (CCP) syndrome in human, such as thermal hyperalgesia, mechanical allodynia
      and autotomy, were present in these rats after spinal cord injury. Meanwhile,
      wide dynamic range (WDR) neurons recorded in the spinal dorsal horn rostral to
      the lesion responded as high frequency of spontaneous activities, long duration
      of after-discharges to noxious electrical stimuli and an augmented wind-up to 0.5
      Hz stimuli. By using bupivacaine powder, a sodium channel blocker, at the locus
      of transection immediate after nerve injury, the chronic pain behaviors were
      prevented; the hyperexcitability of WDR neurons was also substantially reduced.
      It is suggested that spinal cord transection induces the CCP syndromes, which may
      be evoked and maintained by the hyperexcitability in WDR neurons rostrally.
      Reducing the neuronal activity at the site of lesion following injury may prevent
      the development of CCP after SCI.

PMID- 16083865
TI  - Bilateral enhancement of excitation via up-regulation of vesicular glutamate
      transporter subtype 1, not subtype 2, immunoreactivity in the unilateral hypoxic
      epilepsy model.
AB  - In the present study, the change of vesicular glutamate transporter (VGLUT)
      immunoreactivity on long-term impaired excitability in the hippocampus after
      recovery from unilateral hypoxic-ischemic insult was investigated in order to
      extend our understanding of the mechanism of epileptogenesis using unilateral
      hypoxic epilepsy models. Both the lesioned (submitted to ischemia) and the
      unlesioned hippocampi exhibited the frequent occurrence of interictal spikes and
      occasionally the sustained ictal discharges. However, paired-pulse inhibition was
      significantly reduced in the unlesioned dentate gyrus, not in the lesioned
      dentate gyrus. VGLUT1 immunoreactivity was significantly elevated in both
      hippocampi following hypoxic ischemia, although VGLUT2 immunodensity was
      unaltered. These findings suggest that the enhancement of VGLUT1 immunoreactivity
      in both hippocampi after unilateral hypoxic ischemia may contribute to the
      hyperexcitability, which may play an important role in the epileptogenesis
      (presumably accompanied by altered inhibitory transmission) after
      neurodegeneration.

PMID- 16083866
TI  - Tyrosine administration does not affect desipramine-induced dopamine levels as
      measured in vivo in prefrontal cortex.
AB  - Using in vivo microdialysis, we examined whether tyrosine administration would
      potentiate the desipramine (DMI)-induced elevation of medial prefrontal cortex
      (MPFC) dopamine (DA) levels. DMI (10 or 20 mg/kg IP) increased MPFC DA levels but
      not DOPA accumulation. Tyrosine (12.5-100 mug/ml) administered by reverse
      microdialysis did not affect DMI-induced MPFC DA levels. The data support our
      hypothesis that DA synthesis must be significantly increased in order for
      administered tyrosine to increase extracellular DA levels.

PMID- 16083867
TI  - Ca2+-dependent reduction of IK1 in rat ventricular cells: a novel paradigm for
      arrhythmia in heart failure?
AB  - OBJECTIVES: We investigated the inward rectifier potassium current (I(K1)), which
      can be blocked by intracellular Ca(2+), in heart failure (HF). METHODS: We used
      the whole-cell patch-clamp technique to record I(K1) from single rat ventricular
      myocytes in voltage-clamp conditions. Fluorescence measurements of diastolic
      Ca(2+) were performed with Indo-1 AM. HF was examined 8 weeks after myocardial
      infarction (coronary artery ligation). RESULTS: I(K1) was reduced and diastolic
      Ca(2+) was increased in HF cells. The reduction of I(K1) was attenuated when EGTA
      was elevated from 0.5 to 10 mM in the patch pipette and prevented with high BAPTA
      (20 mM). Ryanodine (100 nM) and FK506 (10 microM), both of which promote
      spontaneous SR Ca(2+) release from ryanodine receptor (RyR2) during diastole,
      reproduced the effect of HF on I(K1) in normal cells but had no effect in HF
      cells. The effects of ryanodine and FK506 were not additive and were prevented by
      BAPTA. Rapamycin (10 microM), which removes FKBP binding proteins from RyR2 with
      no effect on calcineurin, mimicked the effect of FK506 on I(K1). Cyclosporine A
      (10 microM), which inhibits calcineurin via cyclophilins, had no effect. In both
      HF cells and normal cells treated by FK506, the protein kinase C (PKC) inhibitor
      staurosporine totally restored the inward component of I(K1), but only partially
      restored its outward component at potentials corresponding to the late
      repolarizing phase of the action potential (-80 to -40 mV). CONCLUSIONS: I(K1) is
      reduced by elevated diastolic Ca(2+)in HF, which involves in parallel PKC
      dependent and PKC-independent mechanisms. This regulation provides a novel
      paradigm for Ca(2+)-dependent modulation of membrane potential in HF. Since
      enhanced RyR2-mediated Ca(2+)release also reduces I(K1), this paradigm might be
      relevant for arrhythmias related to acquired or inherited RyR2 dysfunction.

PMID- 16083868
TI  - Activated mouse T-cells synthesize MHC class II, process, and present
      morbillivirus nucleocapsid protein to primed T-cells.
AB  - A pivotal step in the initiation of T-cell immunity is the presentation of
      antigenic peptides by major histocompatibility complex (MHC) expressed on antigen
      presenting cells. The expression of MHC class II molecules by mouse T-cells has
      not been shown unequivocally. In the present work, we demonstrate that activated
      mouse T-cells synthesize MHC class II molecules de novo and express them on their
      surface. Further, we have demonstrated that in vitro activated T-cells take up
      extra-cellular soluble nucleocapsid protein of a morbillivirus. The internalized
      antigen goes to antigen processing compartment as shown by co-localization of
      antigen and LAMP-1 using confocal microscopy. We show that activated T-cells
      express H2M, a chaperone molecule known to have a role in antigen presentation.
      Further, we demonstrate that activated T-cells process and present internalized
      extra-cellular antigen to primed T-cells as shown by IL-2 secretion and in vitro
      proliferation. The presentation of antigen by T-cells may have implications in
      immuno-regulation, control of infection by lymphotropic viruses and maintenance
      of immunological memory.

PMID- 16083869
TI  - T cell expansion is regulated by activated Gr-1+ splenocytes.
AB  - CD4+ T cell proliferation depends on the balance between NO and extra-cellular
      superoxide (O2-). By reducing NO bio-availability, O2- promotes splenic T cell
      proliferation and immune response intensity. Here, we show that spleen cells from
      naive mice produced neither NO nor O2- during T cell activation, but Gr-1+
      splenocytes from primed mice regulated Ag-specific T cell expansion via
      production of both molecules. Purified splenic Gr-1+ cells included mostly
      granulocytes at various stages of maturation, as well as monocytes. Activation or
      recruitment of regulatory Gr-1+ cells was dependent on immunization with CFA.
      Importantly, these regulatory cells were not detected in draining lymph nodes.
      These data suggest that innate Gr-1+ splenic cells regulate adaptive immunity.

PMID- 16083870
TI  - Production of biologically active recombinant human soluble CD23 and its effect
      on PBMCs isolated from hyper-IgE blood.
AB  - A recombinant form of human soluble CD23 (sCD23), the low affinity receptor for
      IgE (FcepsilonRII), was produced by PCR cloning the lectin-binding domain
      sequence into a bacterial expression vector. After renaturation and purification,
      the sCD23 bound IgE and divalent metal ions, indicating its activity. The
      recombinant human sCD23 exhibited similar proinflammatory properties as the
      native protein. Although interleukin-1beta, tumour necrosis factor-alpha, and
      nuclear factor-kappaB appeared not to be enhanced significantly in unstimulated
      RPMI 8866 B-lymphoblastoid and U937 promonocytic cell lines with 24 h incubation
      of recombinant sCD23, they were produced in both healthy and hyper-IgE-derived
      peripheral blood mononuclear cells, especially tumour necrosis factor-alpha. This
      study concludes that while recombinant and chimeric sCD23 may be useful in
      blocking IgE binding to immune cells and decreasing IgE synthesis by B
      lymphocytes, the production of proinflammatory cytokines, particularly tumour
      necrosis factor-alpha will enhance immune responses in cases of asthma, allergy,
      and hyper-IgE syndrome.

PMID- 16083871
TI  - Interaction between copper and zinc in metal accumulation in rats with particular
      reference to the synthesis of induced-metallothionein.
AB  - The effectiveness of Zn at moderating the pro-oxidant effects of Cu was evaluated
      in two rat models that differed in the route and mode of administration. The
      endpoints investigated included measurement of the concentrations of Cu, Zn,
      metallothionein and glutathione concentrations, as well as SOD and catalase
      activity, in liver, kidneys and intestine. In a sub-chronic animal model, the
      hepatic accumulation of Cu was achieved by administration of dietary Cu (1.8 g/kg
      solid diet) for 30 days after which oral Zn (6g/kg solid diet) was given. Cu
      treatment induced an increase in the hepatic and intestinal concentration of Cu
      of 66 and 455%, respectively, that was not associated with synthesis of
      metallothionein synthesis, but rather appeared to be related to the higher
      activity of SOD. Subsequent administration with Zn after dietary Cu induced an
      increase in the hepatic and intestinal metallothionein content of more twice and
      reduced the Cu content to control values. Thus, Zn could act as both a competitor
      for absorption on the luminal side of the intestinal epithelium inducing the
      synthesis of metallothionein. In the second animal model, we studied the effects
      of interaction between Cu and Zn administered by i.p. injection at the dose of 3
      and 10mg/kg, respectively; Zn was administered subsequent to Cu overload. In this
      case, when Zn was administered, Cu was already deposited in tissues and thus
      there is no competition between two metals at the level of membrane transport. In
      this experimental model treatment with Cu alone induced liver metallothionein
      synthesis, and the subsequent treatment with Zn did not decrease the hepatic
      content of Cu. One explanation for these observations is that Zn induces the
      synthesis of metallothionein, which binds Cu for which it has a higher affinity.
      Moreover, after treatment with Zn, SOD activity in the liver decreases of almost
      30% with respect to treatment with alone Cu, suggesting that Zn has a protective
      effect.

PMID- 16083872
TI  - Pax3/7 genes reveal conservation and divergence in the arthropod segmentation
      hierarchy.
AB  - Several features of Pax3/7 gene expression are shared among distantly related
      insects, including pair-rule, segment polarity, and neural patterns. Recent data
      from arachnids imply that roles in segmentation and neurogenesis are likely to be
      played by Pax3/7 genes in all arthropods. To further investigate Pax3/7 genes in
      non-insect arthropods, we isolated two monoclonal antibodies that recognize the
      products of Pax3/7 genes in a wide range of taxa, allowing us to quickly survey
      Pax3/7 expression in all four major arthropod groups. Epitope analysis reveals
      that these antibodies react to a small subset of Paired-class homeodomains, which
      includes the products of all known Pax3/7 genes. Using these antibodies, we find
      that Pax3/7 genes in crustaceans are expressed in an early broad and, in one
      case, dynamic domain followed by segmental stripes, while myriapods and
      chelicerates exhibit segmental stripes that form early in the posterior-most part
      of the germ band. This suggests that Pax3/7 genes acquired their role in
      segmentation deep within, or perhaps prior to, the arthropod lineage. However, we
      do not detect evidence of pair-rule patterning in either myriapods or
      chelicerates, suggesting that the early pair-rule expression pattern of Pax3/7
      genes in insects may have been acquired within the crustacean-hexapod lineage.

PMID- 16083873
TI  - Phenolsulfonphthalein transport by potential-sensitive urate transport system.
AB  - The purpose of this study was to elucidate the transporter-mediated secretion
      systems for phenolsulfonphthalein in brush-border membranes. In human and rat
      renal brush-border membranes, a potential-sensitive transport system has been
      shown to be involved in the efflux of organic anions. The uptake of
      phenolsulfonphthalein into rat renal brush-border membrane vesicles was
      stimulated by an inside-positive membrane potential. This potential-sensitive
      uptake of phenolsulfonphthalein was inhibited by probenecid, pyrazinoate and
      urate. p-Aminohippurate had no effect on the potential-sensitive uptake of
      phenolsulfonphthalein. Moreover, urate competitively inhibited the uptake of
      phenolsulfonphthalein. On the other hand, the uptake of phenolsulfonphthalein was
      slightly increased in the presence of an outward Cl- gradient. These results
      suggest that phenolsulfonphthalein has high affinity for the potential-sensitive
      urate transport system but has low affinity for an anion exchanger.

PMID- 16083874
TI  - Electrophysiological effects of azimilide in an in vitro model of simulated
      ischemia and reperfusion in guinea-pig ventricular myocardium.
AB  - There are few investigations on azimilide effects during ischemia/reperfusion. We
      have therefore investigated low concentrations of azimilide (0.1 and 0.5
      micromol/l) versus Controls on action potential parameters and occurrence of
      repetitive responses during simulated ischemia and reperfusion. An in vitro model
      of "border zone" in guinea-pig ventricular myocardium (n=30) was used. Azimilide
      0.5 micromol/l lengthened action potential duration in normoxic but not in
      ischemic-like conditions. Therefore an increased dispersion of action potential
      duration at 90% of repolarization during simulated ischemia in presence of
      azimilide was seen. Upon reperfusion, both normal and reperfused myocardium
      showed azimilide-induced action potential duration increase. There was a neutral
      effect on the occurrence of arrhythmias during simulated ischemia; however
      azimilide showed significant (P=0.033) antiarrhythmic properties following
      reperfusion. To mimic I(Kr) and I(Ks) blocking properties of azimilide we further
      used dofetilide 10 nmol/l with HMR 1556 1 nmol/l (N=9), which was accompanied by
      less severe shortening (P<0.05) of action potential duration at 90% of
      repolarization at 30 min of ischemic-like conditions (-43+/-9%), as compared with
      azimilide 0.5 micromol/l (-64+/-5%) but similar to what seen with azimilide 0.1
      micromol/l (-53+/-5%) and Controls (-52+/-6%). During reperfusion, 2/9 (22%)
      preparations had sustained activities, which was less than what observed in
      Controls (5/10, 50%) and with azimilide 0.5 micromol/l (0/10, 0%), although not
      statistically different (respectively, P=0.35 and P=0.21). Lack versus homogenous
      class III effects of azimilide in respectively simulated ischemia and reperfusion
      may explain its different efficacy on arrhythmias, although prevention of
      reperfusion arrhythmias calls for other than just its I(Kr) and I(Ks) blocking
      properties.

PMID- 16083876
TI  - Met identification on human platelets: role of hepatocyte growth factor in the
      modulation of platelet activation.
AB  - Circulating HGF is significantly increased in a number of thrombus-associated
      disorders. Since platelets play a pivotal role in thrombogenesis, the ability of
      HGF to interact with human platelets was investigated. This paper shows for the
      first time that human platelets express HGF receptor, the tyrosine kinase encoded
      by c-MET gene. At physiological concentrations HGF was found to inhibit both
      glycoprotein (alpha)IIb(beta)3 activation and thrombin-dependent platelet
      aggregation in a dose- and time-dependent manner. These results suggest that
      circulating HGF may counteract thrombogenesis by negatively modulating platelet
      functions.

PMID- 16083875
TI  - Proteome profiling of corneal epithelium and identification of marker proteins
      for keratoconus, a pilot study.
AB  - The purpose of this study is to identify corneal proteins differentially
      expressed between keratoconus and normal epithelial samples. Proteins from the
      corneal epithelium were isolated from 6 keratoconus and 6 myopia patients
      (controls) and separated by 2D-gel electrophoresis. Six % and 12% SDS-PAGE gels
      were used to separate low and high molecular weight proteins. Gels were silver
      stained and protein spots were defined by Melanie II software. The proteins that
      were most altered in expression comparing keratoconus and controls were
      extracted, trypsin-digested, and identified by mass spectroscopy. Approximately
      200-500 protein spots were detected on each gel. Nineteen spots were identified
      as differentially expressed between keratoconus and reference epithelium
      including cytokeratin 3 (< 7.8 fold), gelsolin (1.6 fold), S100A4 (1.9 fold), and
      enolase 1 (0.72 fold). Another identified protein found at very high levels was
      cytokeratin 12. Gelsolin, cytokeratin 3, and cytokeratin 12 have previously been
      described to be involved in other corneal diseases. Three proteins, gelsolin,
      alpha enolase, and S100A4 were identified to be differentially expressed in
      keratoconus compared to reference epithelium and thus may be involved in the
      pathogenesis.

PMID- 16083878
TI  - In vitro selection of DNA binding sites for ABF1 protein from Saccharomyces
      cerevisiae.
AB  - The autonomously replicating sequence-binding factor 1 (ABF1) from Sacchramoyces
      cerevisiae is known as a multifunctional DNA binding protein that is involved in
      transcriptional regulation, DNA-replication, and in restructuring of chromatin
      via nucleosome remodelling. ABF1 binds to DNA sequences found in ARS elements and
      in various transcriptional regulatory elements. This led to the early definition
      of the consensus motive 5'-CGTnnnnnnnGA(G/C)-3'. We have used a SELEX approach to
      expand and better characterize the DNA sequence requirements of ABF1. Starting
      from a pool of oligonucleotides randomized at a sequence of 30 nucleotides, we
      used EMSA to select for sequences with high affinity for ABF1. We obtained the
      sequences of 106 aptamers after the 15th SELEX round. A 16 nucleotide consensus
      was derived from this pool by analysis with the motif search programme MEME.
      Quantitative EMSA experiments verified our experimental approach since binding
      sequences which were bound with high affinity occurred more often in the pool and
      resembled the derived consensus to a higher degree. We found DNA sequences that
      are bound by ABF1 with nearly two-magnitude higher affinity as compared to the
      hitherto accepted ABF1 consensus sequence. This led us to postulate a strong
      recognition motive: 5'-TnnCGTnnnnnnTGAT-3'.

PMID- 16083877
TI  - Reactive oxygen species-linked regulation of the multidrug resistance transporter
      P-glycoprotein in Nox-1 overexpressing prostate tumor spheroids.
AB  - Expression of the multidrug resistance (MDR) transporter P-glycoprotein (P-gp)
      has been demonstrated to be regulated by hypoxia-inducible factor-1alpha (HIF
      1alpha) and inhibited by intracellular reactive oxygen species (ROS). Herein, P
      gp and HIF-1alpha expression were investigated in multicellular prostate tumor
      spheroids overexpressing the ROS-generating enzyme Nox-1 in comparison to the
      mother cell line DU-145. In Nox-1-overexpressing tumor spheroids (DU-145Nox1)
      generation of ROS as well as expression of Nox-1 was significantly increased as
      compared to DU-145 tumor spheroids. ROS generation was significantly inhibited in
      the presence of the NADPH-oxidase antagonists diphenylen-iodonium chloride (DPI)
      and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF). Albeit growth kinetic of DU
      145Nox1 tumor spheroids was decreased as compared to DU-145 spheroids, elevated
      expression of Ki-67 was observed indicating increased cell cycle activity. In DU
      145Nox1 tumor spheroids, expression of HIF-1alpha as well as P-gp was
      significantly decreased as compared to DU-145 spheroids, which resulted in an
      increased retention of the anticancer agent doxorubicin. Pretreatment with the
      free radical scavengers vitamin E and vitamin C increased the expression of P-gp
      as well as HIF-1alpha in Nox-1-overexpressing cells, whereas no effect of free
      radical scavengers was observed on mdr-1 mRNA expression. In summary, the data of
      the present study demonstrate that the development of P-gp-mediated MDR is
      abolished under conditions of elevated ROS levels, suggesting that the MDR
      phenotype can be circumvented by modest increase of intracellular ROS generation.

PMID- 16083879
TI  - Gelatin binding to the 8F19F1 module pair of human fibronectin requires site
      specific N-glycosylation.
AB  - The gelatin (denatured collagen) binding domain of the extracellular matrix
      protein fibronectin contains three potential N-glycosylation sites. Complete
      deglycosylation of this domain is known to reduce the thermal stability of the
      eighth type 1 (8F1) module. We have conducted a site-specific analysis of the
      structural and functional consequences of N-linked glycosylation in the 8F19F1
      module pair. Three glycoforms have been identified by mass spectrometry and
      nuclear magnetic resonance spectroscopy. Chemical shift differences between the
      glycoforms have revealed an intimate interaction between one N-linked sugar and
      the polypeptide that is critical for gelatin binding, as shown by affinity
      chromatography.

PMID- 16083880
TI  - A unified framework for unraveling the functional interaction structure of a
      biomolecular network based on stimulus-response experimental data.
AB  - We propose a unified framework for the identification of functional interaction
      structures of biomolecular networks in a way that leads to a new experimental
      design procedure. In developing our approach, we have built upon previous work.
      Thus we begin by pointing out some of the restrictions associated with existing
      structure identification methods and point out how these restrictions may be
      eased. In particular, existing methods use specific forms of experimental
      algebraic equations with which to identify the functional interaction structure
      of a biomolecular network. In our work, we employ an extended form of these
      experimental algebraic equations which, while retaining their merits, also
      overcome some of their disadvantages. Experimental data are required in order to
      estimate the coefficients of the experimental algebraic equation set associated
      with the structure identification task. However, experimentalists are rarely
      provided with guidance on which parameters to perturb, and to what extent, to
      perturb them. When a model of network dynamics is required then there is also the
      vexed question of sample rate and sample time selection to be resolved. Supplying
      some answers to these questions is the main motivation of this paper. The
      approach is based on stationary and/or temporal data obtained from parameter
      perturbations, and unifies the previous approaches of Kholodenko et al. (PNAS 99
      (2002) 12841-12846) and Sontag et al. (Bioinformatics 20 (2004) 1877-1886). By
      way of demonstration, we apply our unified approach to a network model which
      cannot be properly identified by existing methods. Finally, we propose an
      experiment design methodology, which is not limited by the amount of parameter
      perturbations, and illustrate its use with an in numero example.

PMID- 16083881
TI  - Regulation of Nod1 by Hsp90 chaperone complex.
AB  - Nod1 and Nod2 proteins play important roles in mammalian innate immune responses
      as intracellular sensors for bacterial peptidoglycan. Nod1 and Nod2 share
      structural homology with many R proteins involved in plant disease resistance. It
      has been demonstrated that plant Hsp90 and its co-chaperone RAR1 are implicated
      in R-mediated disease resistance. Here the Chp-1 gene encoding a mammalian
      homologue of plant RAR1 was identified as a new target for transcriptional
      activation by heat shock factor 1 (HSF1), a stress-responsive HSF isoform. In
      addition, Nod1 is demonstrated to be a client protein of the Hsp90 chaperone
      complex containing the Chp-1. Chp-1 interacts with the tetratricopeptide repeat
      (TPR) domain of protein phosphatase 5 (PP5) and the ATPase domain of Hsp90 via
      two distinct zinc-binding cysteine and histidine rich domains (CHORDs). These
      findings suggest a common regulatory mechanism involving the Hsp90 chaperone
      complex in R-mediated disease resistance in plants and Nod1-mediated innate
      immune response in mammals.

PMID- 16083882
TI  - Tendon xanthomas in familial hypercholesterolemia are associated with a
      differential inflammatory response of macrophages to oxidized LDL.
AB  - Tendon xanthomas (TX) are pathognomonic lipid deposits commonly found in familial
      hypercholesterolemia (FH) patients. The aim of this study was to determine
      whether macrophages from FH patients with TX (TX+) have higher predisposition to
      foam cells formation after oxidized LDL (oxLDL) overload than those from FH
      patients without TX (TX-), and if their differential gene expression profile
      could explain these different phenotypes. Total RNA pools from macrophages from
      FH patients TX+ and TX- were analyzed using Affymetrix oligonucleotide arrays to
      evaluate the gene expression profile in presence and absence of oxLDL. Also, the
      intracellular lipid content was measured by fluorescence flow cytometry. Results
      of these studies suggest that macrophages from FH subjects TX+ compared to those
      TX- have a differential response to oxLDL, since they show higher intracellular
      cholesterol ester accumulation and a differential gene expression profile. The
      gene array data were validated by relative quantitative real-time RT-PCR and
      quantitative ELISA in culture media and plasma samples. FH subjects TX+ showed
      increased plasma tryptase, TNF-alpha, IL-8 and IL-6 concentrations. We propose
      that TX formation are associated with higher intracellular lipid content, and
      higher inflammatory response of macrophages in response to oxLDL.

PMID- 16083883
TI  - Re-evaluating the role of strongly charged sequences in amphipathic cell
      penetrating peptides:    a fluorescence study using Pep-1.
AB  - Cell-penetrating peptides (CPPs) are able to translocate across biological
      membranes and deliver bioactive proteins. Cellular uptake and intracellular
      distribution of CPPs is commonly evaluated with fluorescent labels, which can
      alter peptide properties. The effect of carboxyfluorescein label in the Lys-rich
      domain of the amphipathic CPP pep-1, was evaluated and compared with non-labelled
      pep-1 in vitro and in vivo. A reduced membrane affinity and an endosomal
      dependent translocation mechanism, at variance with non-labelled pep-1, were
      detected. Therefore, the charged domain is not a mere enabler of peptide
      adsorption but has a crucial role in the translocation pathway of non-labelled
      pep-1.

PMID- 16083884
TI  - Crystal structure of a mutant elongation factor G trapped with a GTP analogue.
AB  - Elongation factor G (EF-G) is a G protein factor that catalyzes the translocation
      step in protein synthesis on the ribosome. Its GTP conformation in the absence of
      the ribosome is currently unknown. We present the structure of a mutant EF-G
      (T84A) in complex with the non-hydrolysable GTP analogue GDPNP. The crystal
      structure provides a first insight into conformational changes induced in EF-G by
      GTP. Comparison of this structure with that of EF-G in complex with GDP suggests
      that the GTP and GDP conformations in solution are very similar and that the
      major contribution to the active GTPase conformation, which is quite different,
      therefore comes from its interaction with the ribosome.

PMID- 16083885
TI  - The use of abscisic acid analogues to analyse the substrate selectivity of
      UGT71B6, a UDP-glycosyltransferase of Arabidopsis thaliana.
AB  - This study analyses the activity of an Arabidopsis thaliana UDP
      glycosyltransferase, UGT71B6 (71B6), towards abscisic acid (ABA) and its
      structural analogues. The enzyme preferentially glucosylated ABA and not its
      catabolites. The requirement for a specific chiral configuration of (+)-ABA was
      demonstrated through the use of analogues with the chiral centre changed or
      removed. The enzyme was able to accommodate extra bulk around the double bond of
      the ABA ring but not alterations to the 8'- and 9'-methyl groups. Interestingly,
      the ketone of ABA was not required for glucosylation. Bioactive analogues,
      resistant to 8'-hydroxylation, were also poor substrates for conjugation by
      UGT71B6. This suggests the compounds may be resistant to both pathways of ABA
      inactivation and may, therefore, prove to be useful agrochemicals for field
      applications.

PMID- 16083886
TI  - Sodium channel activators: model of binding inside the pore and a possible
      mechanism of action.
AB  - Sodium channel activators, batrachotoxin and veratridine, cause sodium channels
      to activate easier and stay open longer than normal channels. Traditionally, this
      was explained by an allosteric mechanism. However, increasing evidence suggests
      that activators can bind inside the pore. Here, we model the open sodium channel
      with activators and propose a novel mechanism of their action. The activator
      bound channel retains a hydrophilic pathway for ions between the ligand and
      conserved asparagine in segment S6 of repeat II. One end of the activator
      approaches the selectivity filter, decreasing the channel conductance and
      selectivity. The opposite end reaches the gate stabilizing it in the open state.

PMID- 16083887
TI  - Estrogen facilitates fear conditioning and increases corticotropin-releasing
      hormone mRNA expression in the central amygdala in female mice.
AB  - Estrogens exert important actions on fear and anxiety-like behavior both in
      humans and non-human animals. Currently, the mechanisms underlying estrogenic
      modulation of fear are not known. However, evidence suggests that estrogens may
      exert their influence on fear within the amygdala. The purpose of the present
      study was to examine effects of estrogen on fear conditioning. Specifically, the
      present study examined whether long-term estrogen treatment in ovariectomized
      female mice via Silastic capsule implantation would facilitate both contextual
      and cued fear conditioning. In a separate set of experiments, we then examined
      whether estrogen treatment in ovariectomized female mice would modulate
      corticotropin-releasing hormone (CRH) gene expression within the amygdala. Long
      term estrogen treatment facilitated both contextual and cued fear. Ovariectomized
      mice treated with estrogen froze significantly more to a context as well as to a
      discrete auditory cue. In addition, estrogen treatment significantly increased
      CRH mRNA expression within the central nucleus of the amygdala as measured by in
      situ hybridization and quantitative PCR. These data raise the possibility that
      estrogens could influence fear responses in females through their actions in the
      amygdala.

PMID- 16083888
TI  - Doppler ultrasound assessment and serum cancer antigen 125 in the diagnosis of
      ovarian tumors.
AB  - OBJECTIVE: To differentiate benign from malignant ovarian tumors based on
      sonographic detection of a solid component. METHOD: Sixty-three women with
      ovarian masses were evaluated preoperatively by gray scale and power/color
      Doppler ultrasonographic examination, with specific predefined criteria for the
      solid component. Sensitivity, specificity, and positive and negative predictive
      values were calculated and assessed against the histopathologic outcome. The
      contribution of cancer antigen (CA) 125 levels to the diagnostic accuracy was
      also assessed. RESULT: Sensitivity, specificity, and positive and negative
      predictive values were 100%, 95.2%, 91.3% and 100%, respectively, with two false
      positive results. Had an elevated CA 125 level (>35 U/mL) been included in the
      malignancy criteria, the false-positive results would have been eliminated,
      giving an accuracy of 100%. CONCLUSION: Sonographic evaluation with predefined
      specific criteria for the detection of a solid tumor component is an accurate
      method of preoperative discrimination between benign and malignant ovarian
      tumors. A serum CA 125 assay may assist in eliminating false-positive results.

PMID- 16083889
TI  - Re: Determination of mechanical stiffness of bone by qPCT measurements:
      correlation with non-destructive mechanical four-point bending test data by
      Matrin et al., J. Biomech., 2004, Vol. 37, pp. 1289-1293.

PMID- 16083890
TI  - Evaluation of the superficial characteristics of articular cartilage using
      evanescent waves in the friction tests with intermittent sliding and loading.
AB  - Articular cartilage plays an important role in the lubrication of synovial joints
      because of its peculiar characteristics. In this work, the frictional and
      superficial characteristics of articular cartilage were evaluated simultaneously
      during intermittent sliding and loading. The apparatus used for the analysis of
      the articular surface was based on the evanescent waves, where a laser light was
      reflected at the interface between a prism and a specimen of articular cartilage.
      Friction forces were measured due to the sliding of specimens on the prism.
      Images of reflected light were analyzed and attenuation of the reflectance was
      associated with the presence of collagen fibers near the interface, which
      interacted with the evanescent waves because of the high refractive index of
      these fibers. Specimens were tested in the intervals of 5.5 min with an
      interruption of 10 and 30 s in the sliding and loading. Results indicated a
      decrease in the both friction coefficient and attenuation of reflectance after
      the unloading. The level of reduction of the friction as well as of the
      attenuation of reflectance increased as the time of unloading increased. Decrease
      of friction after unloading was related to the decrease of collagen contents, or
      increase in water contents, at the articular surface, which was observed through
      the decrease of the attenuation of reflectance. Results indicated that the
      increase in the water content at the articular surface and the rehydration
      ability of articular cartilage after unloading could be responsible for the
      maintenance of friction in low levels.

PMID- 16083891
TI  - Effect of chelating functional polymer on the size of CdS nanocluster formation.
AB  - Chelating poly(acrylates-co-2-methylacrylic acid 3-(bis-carboxymethylamino)-2
      hydroxy-propyl ester) microspheres of diameter 250-310 nm were prepared by the
      soap-free emulsion polymerization method for varying amounts of GMA-IDA. Then
      CdS/copolymer composite was generated by chemical deposition on the surface of
      the copolymer microspheres. By XRD analysis it is found that the chelated CdS
      nanoparticles are a pure cubic zinc blende structure. The CdS/copolymer composite
      is examined by UV-vis absorbance, photoluminescence, and TEM observation. Average
      CdS nanoparticle size calculated from Henglein's empirical curve is in the range
      of 3.0-8.0 nm and varies according to the GMA-IDA molar ratio during
      polymerization, pH value during chelation, and postchelation annealing
      temperature. Higher ratio of chelating group, pH value, and annealing temperature
      produce larger CdS nanoparticles. As GMA-IDA ratio increases, photoluminescence
      exhibits a red shift from 510 to 520 nm, photoluminescence increases, and
      bandwidth decreases. Photoluminescence of the CdS nanoparticle becomes negligible
      when diameter exceeds 5 nm.

PMID- 16083892
TI  - Pillaring effects in macroporous carrageenan-silica composite microspheres.
AB  - The impregnation of a carrageenan gel by a silica sol is an efficient method to
      form a composite material which can be conveniently activated by CO2
      supercritical drying. The textural properties of the solids have been
      characterized by nitrogen adsorption-desorption at 77 K and their composition by
      thermogravimetric analysis and EDX microprobe. Morphology was examined by SEM.
      The silica-carrageenan composites present an open macroporous structure. Silica
      particles retained inside the gel behaved as pillars between the polysaccharide
      fibrils and form a stick-and-ball network. The stiffening of the carrageenan gel
      by silica prevented its shrinkage upon drying. The nature of the alkali cations
      affected the retention of silica particles inside the gel. In the absence of
      silica, carrageenan fibrils rearrange under supercritical drying and form an
      aerogel with cavities in the mesopore range.

PMID- 16083893
TI  - Surface modification of crosslinked poly(styrene-divinyl benzene) micrometer
      sized particles of narrow size distribution by ozonolysis.
AB  - Micrometer-sized polystyrene template particles of narrow size distribution were
      prepared by dispersion polymerization of styrene in 2-methoxyethanol. Uniform
      micrometer-sized polystyrene/crosslinked poly(styrene-divinyl benzene) composite
      particles were formed by a single-step swelling process of the template particles
      with styrene, divinyl benzene and benzoyl peroxide, followed by polymerization at
      70 degrees C. Uniform micrometer-sized crosslinked poly(styrene-divinyl benzene)
      particles of higher surface area were produced by dissolution of the template
      polystyrene part of the former composite particles with N,N-dimethylformamide.
      Hydroperoxide conjugated crosslinked poly(styrene-divinyl benzene) particles were
      produced by ozonolysis of these particles. The effect of ozonolysis conditions,
      such as exposure time and flow rate of the ozone, on the hydroperoxide
      conjugation to the crosslinked particles was also studied. Functionalization of
      the crosslinked poly(styrene-divinyl benzene) particles was performed by graft
      polymerization of vinylic monomers such as acrylonitrile and chloromethylstyrene
      on the hydroperoxide conjugated crosslinked particles. This was accomplished by
      raising the temperature (e.g., 70 degrees C) of deairated acetonitrile
      dispersions containing the hydroperoxide conjugated particles and the vinylic
      monomers. The influence of various polymerization parameters on the grafting
      yield, e.g., monomer concentration, conjugated hydroperoxide concentration, and
      temperature, was also elucidated.

PMID- 16083894
TI  - Online kinetic studies on intermediates of laccase-catalyzed reaction in reversed
      micelle.
AB  - Using water/AOT/n-octane reversed micelle as the medium, the optical signal of
      the reactive intermediate of laccase-catalyzed oxidation of o-phenylenediamine,
      which was indetectable in aqueous solutions, was successfully captured. Thus
      online kinetic studies of the intermediate were accomplished. Two-way kinetic
      spectral data were acquired with stopped-flow technique. By resolving the data
      with global analysis software, both the kinetic curves and the absorption spectra
      of the components involved in the reaction process were simultaneously obtained.
      The whole reaction in the reversed micelle was proved to be composed of two
      successive steps, an enzymatic generation of the intermediate and a following
      nonenzymatic decay of the intermediate. A consecutive first-order kinetic model
      of the whole reaction was confirmed. The influences of microenvironmental factors
      of the medium (such as the pH value of the water pool and the water/AOT ratio) on
      the detection of the intermediate were also investigated.

PMID- 16083895
TI  - Effect of heat treatment on the physico-chemical properties and catalytic
      activity of manganese nodules leached residue towards decomposition of hydrogen
      peroxide.
AB  - The effect of calcination temperature on the physico-chemical characterization of
      manganese nodule leached residue (MNLR) and water-washed manganese nodule leached
      residue (WMNLR) has been investigated on the basis of chemical analysis, XRD, TG
      DTA, FTIR, surface hydroxyl groups, surface oxygen, reducing and oxidizing sites,
      surface area. XRD and IR confirm the presence of amorphous iron oxyhydroxides,
      delta-MnO2, which are converted to alpha-Fe2O3 and gamma-Mn2O3 phases above 400
      degrees C of calcination, respectively. A solid solution of Fe2O3 and Mn2O3 is
      formed above 700 degrees C. The surface area, surface hydroxyl group, surface
      oxygen, reducing and oxidizing sites increase with the increase in calcination
      temperature up to 400 degrees C and then decrease with further rise in
      calcination temperature up to 700 degrees C. The catalytic activity of the sample
      towards H2O2 decomposition shows the similar trend as surface properties. A
      suitable Mn(3+)Mn4+ couple favours H2O2 decomposition reaction. The activity has
      been correlated with various physico-chemical properties.

PMID- 16083896
TI  - Mucin at solution/air and solid/solution interfaces.
AB  - In this paper the surface activity of protein mucin at solution/air interface has
      been studied. The experiments of the adsorbed protein at solution/air interface
      have been carried out with a range of protein concentrations at a defined pH. The
      adsorption of the protein to solid surfaces and the degree of hydrophobicity at
      solid/solution interface of mucin have been evaluated at different pH and in the
      presence of Hofmeister electrolyte. The results from these studies have been
      further substantiated by surface potential measurements of mucin covered surface
      on stainless steel. Quartz crystal microbalance (QCM) has been used to follow the
      protein adsorption kinetics from solution to solid surface. The results from
      these measurements show that the adsorption behavior has a remarkable dependence
      on the degree of maximum coverage and is almost independent of the ionic
      strength. Other characteristic features such as maximum adsorption values at the
      protein isoelectric point (IEP4.7) and low-affinity isotherms that showed surface
      saturation even under unfavorable electrostatic conditions have been observed.
      The amount of mucin adsorbed in the presence of electrolytes has been estimated
      using electron spectroscopy for chemical analysis (ESCA). The study clearly shows
      that there exists an inverse relationship between the hydrophobicity and surface
      tension of the protein and also on the hydrated radius of Hofmeister electrolyte
      used.

PMID- 16083897
TI  - Poly(tetrahydropyranyl-2-methyl methacrylate): comparative study in solution and
      at the air/water interface.
AB  - In this work a comparative study of different molecular-weight fractions of the
      amphiphilic polymer poly(tetrahydropyranyl-2-methyl methacrylate) (PTHPMM) in
      solution and at the air/water interface is reported. The synthesis of the polymer
      was carried out in solution by radical polymerization. The polymer was
      fractionated and five fractions were studied in solution and at the air/water
      interface. The weight-average molecular weight M(w), the second virial
      coefficient A(2), and the radius of gyration R(g) were determined in toluene by
      static light scattering. Intrinsic viscosities [eta] of the polymer fractions in
      three solvents were obtained. The Kuhn-Mark-Houwink-Sakurada relationships were
      established. The Langmuir isotherms for different polymer fractions were obtained
      at the air/water interface by monolayer compression at constant temperature. The
      overlap surface concentrations were determined, and from these results the radius
      of gyration in two dimensions was calculated. The thermodynamic power of the
      toluene and the air/water interface for PTHPMM were estimated from the empirical
      relationship between the radius of gyration in two and three dimensions and the
      weight-average molecular weight.

PMID- 16083898
TI  - The influence of ionic strength on the interaction of viruses with charged
      surfaces under environmental conditions.
AB  - The influence of ionic strength on the electrostatic interaction of viruses with
      environmentally relevant surfaces was determined for three viruses, MS2, Q beta,
      and Norwalk. The virus is modeled as a particle comprised of ionizable amino acid
      residues in a shell surrounding a spherical RNA core of negative charge, these
      charges being compensated for by a Coulomb screening due to intercalated ions. A
      second model of the virus involving surface charges only is included for
      comparison. Surface potential calculations for each of the viruses show excellent
      agreement with electrophoretic mobility and zeta potential measurements as a
      function of pH. The environmental surface is modeled as a homogeneous plane held
      at constant potential with and without a finite region (patch) of opposite
      potential. The results indicate that the electrostatic interaction between the
      virus and the oppositely charged patch is significantly influenced by the
      conditions of ionic strength, pH and size of the patch. Specifically, at pH 7,
      the Norwalk virus interacts more strongly with the patch than MS2 (approximately
      51 vs approximately 9kT) but at pH 5, the Norwalk-surface interaction is
      negligible while that of MS2 is approximately 5.9kT. The resulting ramifications
      for the use of MS2 as a surrogate for Norwalk are discussed.

PMID- 16083899
TI  - Adsorption of Wells-Dawson tungsten heteropolyacid on sol-gel alumina: structural
      features and thermal stability.
AB  - The Wells-Dawson tungsten heteropolyacid, H6P2W18O62 supported on sol-gel and non
      sol-gel alumina has been investigated by infrared spectroscopy (IR), thermal
      analysis (TGA/DSC), and X-ray diffraction (XRD). X-ray diffraction indicates that
      the heteropolyacid primary structure in bulk form holds up to 350 degrees C and
      by supporting it on the sol-gel alumina the thermal stability rose to 650 degrees
      C. UV-vis spectroscopy showed that the sol-gel alumina has a higher tendency to
      adsorb Wells-Dawson tungsten heteropolyacid than the non-sol-gel alumina. The
      heteropolyacid showed higher interaction with the sol-gel alumina than with the
      non-sol-gel. Esterification of propanoic acid with hexanol in the presence of
      alumina-supported heteropolyacid revealed that the acidic character of the
      heteropolyacid remains active to some extent.

PMID- 16083900
TI  - Effect of counterion on the structural switchover and binding of piroxicam with
      sodium dodecyl sulfate (SDS) micelles.
AB  - Addition of an electrolyte such as NaCl to ionic micelles such as sodium dodecyl
      sulfate (SDS) alters the ionic atmosphere of the bulk solvent, thereby changing
      both the micellar properties and the interaction pattern of micelles with a
      molecule in the solvent. In this study, we show how added NaCl in the presence of
      SDS micelles modulates the surface charge of the micelles, which in turn fine
      tunes the switchover equilibrium between anionic and global neutral forms of
      piroxicam. The presence of salt alters the CMC and aggregation number of SDS
      micelles. The binding of the global neutral form of piroxicam with SDS is found
      to be strongly modulated by the presence of counterion in the bulk solvent.

PMID- 16083901
TI  - The costs and benefits of high early mating rates in male stalk-eyed flies,
      Cyrtodiopsis dalmanni.
AB  - Cyrtodiopsis dalmanni stalk-eyed flies have extremely high mating rates. In this
      paper, we examine the fitness costs and benefits of high mating rates, using
      flies with low or high early mating rates. We show that high early mating rates
      are beneficial as they increase the total number of matings gained by a male for
      a given lifespan. However, males with high early mating rates suffer a cost
      through lowered survival. There was no consistent effect of male mating rate on
      female egg production or on male fertility. As higher mating rates are associated
      with larger accessory gland size, we hypothesize that the extra production of
      accessory gland products in high early mating males is responsible for much of
      the cost of reduced longevity.

PMID- 16083902
TI  - Ultrastructural analysis supports transferring Nosema whitei Weiser 1953 to the
      genus Paranosema and creation a new combination, Paranosema whitei.
AB  - The current ultrastructural description of Nosema whitei is in agreement with the
      genus definition of Paranosema [Sokolova, Y.Y., Dolgikh, V.V., Morzhina, E.V.,
      Nassonova, E.S., Issi, I.V., Terry, R.S., Ironside, J.E., Smith, J.E.,
      Vossbrinck, C.R., 2003. Establishment of the new genus Paranosema based on the
      ultrastructure and molecular phylogeny of the type species Paranosema grylli Gen.
      Nov., Comb. Nov (Sokolova, Selezniov, Dolgikh, Issi 1994), from the cricket
      Gryllus bimaculatus Deg. Journal of Invertebrate Pathology 84, 159-172]. In
      addition to exhibiting similar spore morphology and sporogony type, N. whitei,
      like P. grylli and Paranosema locustae, possesses a distinct meront-sporont
      transitional stage in the life cycle; develops in the host fat body, and produces
      secretory material arranged in "tubular structures" during sporogony.
      Ultrastructural analysis supports the similarity of N. whitei to P. grylli and to
      P. locustae as predicted on the basis SSrDNA sequence data (GenBank Accession
      Nos. AY305323, AY305325, and AY305324). Comparative studies of these three
      related species provide a good example of the consistency of morphological and
      sequence data, and support both the placement of N. whitei inside the genus
      Paranosema and the validity of the new combination Paranosema whitei (Weiser).

PMID- 16083903
TI  - Occurrence and characterization of a nucleopolyhedrovirus from Spodoptera
      littoralis (Lepidoptera: Noctuidae) isolated in the azores.
AB  - A nucleopolyhedrovirus (SpliMNPV-Az) was isolated from diseased larvae of
      Spodoptera littoralis, collected at the Island of S. Miguel in Azores. The
      virulence of this isolate was tested against S. littoralis larvae in laboratory.
      LD50 against 2nd and 3rd instars were not significantly different, 1.44x10(4),
      3.89x10(4) OBs per larvae, respectively, but both were significantly different
      from that against 4th instar, which was 61.3x10(4) OBs per larvae. The complete
      codons sequence of SpliMNPV-Az Polh gene obtained was 750 bp (NCBI GenBank
      Accession No. AY600451). This sequence was compared to other 38 polyhedrin genes
      from NPVs and to 6 granulin genes from GVs and resulted to be identical to the
      sequence of a SpliMNPV previously published, thus indicating that the natural
      host of SpliMNPV-Az must be S. littoralis. Genetic distances estimated from
      restriction enzymes profiles showed SpliMNPV-Az is close to the Egyptian SpliMNPV
      type B, despite some degree of genetic divergence suggested by slight differences
      observed on PstI profile.

PMID- 16083904
TI  - Drosophila BAP60 is an essential component of the Brahma complex, required for
      gene activation and repression.
AB  - The SWI/SNF-like chromatin remodeling complex of Drosophila, the Brahma complex,
      contains four subunits (Brahma, BAP155/Moira, SNR1 and BAP60) conserved from
      yeast to humans. A reconstituted human complex lacking the BAP60 homolog shows
      full remodeling activity, suggesting that BAP60 is not essential for the core
      function. We generated Drosophila mutants and found that BAP60 carries a vital
      function and participates in complex-mediated transcriptional activation and
      repression. BAP60 binds DNA and shows genetic and physical interactions with the
      sex-determining transcription factors encoded by sisterless A and scute. The
      results support the conclusion that BAP60 participates in site-specific
      recruitment of the Brahma complex in Drosophila.

PMID- 16083905
TI  - An atomic-level investigation of the disease-causing A629P mutant of the Menkes
      protein, ATP7A.
AB  - Menkes disease is a fatal disease that can be induced by various mutations in the
      ATP7A gene, leading to unpaired uptake of dietary copper. The ATP7A gene encodes
      a copper(I)-translocating ATPase. Here the disease-causing A629P mutation, which
      occurs in the last of the six copper(I)-binding soluble domains of the ATPase
      (hereafter MNK6), was investigated. To understand why this apparently minor amino
      acid replacement is pathogenic, the solution structures and dynamics on various
      time-scales of wild-type and A629P-MNK6 were determined both in the apo- and
      copper(I)-loaded forms. The interaction in vitro with the physiological ATP7A
      copper(I)-donor (HAH1) was additionally studied. The A629P mutation makes the
      protein beta-sheet more solvent accessible, possibly resulting in an enhanced
      susceptibility of ATP7A to proteolytic cleavage and/or in reduced capability of
      copper(I)-translocation. A small reduction of the affinity for copper(I) is also
      observed. Both effects could concur to pathogenicity.

PMID- 16083906
TI  - Structure and dynamics of the homodimeric dynein light chain km23.
AB  - km23 (96 residues, 11 kDa) is the mammalian ortholog of Drosophila roadblock, the
      founding member of LC7/robl/km23 class of dynein light chains. km23 has been
      shown to be serine-phosphorylated following TGFbeta receptor activation and to
      bind the dynein intermediate chain in response to such phosphorylation. Here, we
      report the three-dimensional solution structure of km23, which is shown to be
      that of a homodimer, similar to that observed for the heterodimeric complex
      formed between p14 and MP1, two distantly related members of the MglB/robl
      superfamily, but distinct from the LC8 and Tctex-1 classes of dynein light
      chains, which also adopt homodimeric structures. The conserved surface residues
      of km23, including three serine residues, are located predominantly on a single
      face of the molecule. Adjacent to this face is a large cleft formed by the
      incomplete overlap of loops from opposite monomers. As shown by NMR relaxation
      data collected at two fields, several cleft residues are flexible on the ns-ps
      and ms-mus timescales. Based on these observations, we propose that the patch of
      conserved residues on the central face of the molecule corresponds to the site at
      which km23 binds the dynein intermediate chain and that the flexible cleft formed
      between the overlap of loops from the two monomers corresponds to the site at
      which km23 binds other partners, such as the TGFbeta type II receptor or Smad2.

PMID- 16083907
TI  - Guilty by association: some collagen II mutants alter the formation of ECM as a
      result of atypical interaction with fibronectin.
AB  - Among the structural components of extracellular matrices (ECM) fibrillar
      collagens play a critical role, and single amino acid substitutions in these
      proteins lead to pathological changes in tissues in which they are expressed.
      Employing a biologically relevant experimental model consisting of cells
      expressing R75C, R519C, R789C, and G853E procollagen II mutants, we found that
      the R789C mutation causing a decrease in the thermostability of collagen not only
      alters individual collagen molecules and collagen fibrils, but also has a
      negative impact on fibronectin. We propose that thermolabile collagen molecules
      are able to bind to fibronectin, thereby altering intracellular and extracellular
      processes in which fibronectin takes part, and we postulate that such an atypical
      interaction could change the architecture of the ECM of affected tissues in
      patients harboring mutations in genes encoding fibrillar collagens.

PMID- 16083908
TI  - The formation of Escherichia coli curli amyloid fibrils is mediated by prion-like
      peptide repeats.
AB  - Amyloid fibril formation is the hallmark of major human maladies including
      Alzheimer's disease, type II diabetes, and prion diseases. Prion-like phenomena
      were also observed in yeast. Although not evolutionarily related, one similarity
      between the animal PrP and the yeast Sup35 prion proteins is the occurrence of
      short peptide repeats that are assumed to play a key role in the assembly of the
      amyloid structures. It was recently demonstrated that typical amyloid fibril
      formation is associated with biofilm formation by Escherichia coli. Here, we note
      the functional and structural similarity between oligopeptide repeats of the
      major curli protein and those of animal and yeast prions. We demonstrate that
      synthetic peptides corresponding to the repeats form fibrillar structures.
      Furthermore, conjugation of beta-breaker elements to the prion-like repeat
      significantly inhibits amyloid formation and cell invasion of curli-expressing
      bacteria. This implies a functional role of the repeat in the self-assembly of
      the fibrils. Since mammal prion, yeast prion, and curli protein are
      evolutionarily distinct, the conserved peptide repeats most likely define an
      optimized self-association motif that was independently evolved by diverse
      systems.

PMID- 16083909
TI  - X-ray structure of domain I of the proton-pumping membrane protein
      transhydrogenase from Escherichia coli.
AB  - The dimeric integral membrane protein nicotinamide nucleotide transhydrogenase is
      required for cellular regeneration of NADPH in mitochondria and prokaryotes, for
      detoxification and biosynthesis purposes. Under physiological conditions,
      transhydrogenase couples the reversible reduction of NADP+ by NADH to an inward
      proton translocation across the membrane. Here, we present crystal structures of
      the NAD(H)-binding domain I of transhydrogenase from Escherichia coli, in the
      absence as well as in the presence of oxidized and reduced substrate. The
      structures were determined at 1.9-2.0 A resolution. Overall, the structures are
      highly similar to the crystal structure of a previously published NAD(H)-binding
      domain, from Rhodospirillum rubrum transhydrogenase. However, this particular
      domain is unique, since it is covalently connected to the integral-membrane part
      of transhydrogenase. Comparative studies between the structures of the two
      species reveal extensively differing surface properties and point to the possible
      importance of a rigid peptide (PAPP) in the connecting linker for conformational
      coupling. Further, the kinetic analysis of a deletion mutant, from which the
      protruding beta-hairpin was removed, indicates that this structural element is
      important for catalytic activity, but not for domain I:domain III interaction or
      dimer formation. Taken together, these results have important implications for
      the enzyme mechanism of the large group of transhydrogenases, including mammalian
      enzymes, which contain a connecting linker between domains I and II.

PMID- 16083910
TI  - Implicit and explicit memory in patients with obsessive-compulsive disorder: an
      event-related potential study.
AB  - The implicit and explicit memory in patients with obsessive-compulsive disorder
      (OCD) was investigated using the event-related potential (ERP). For the
      assessment of implicit memory, a lexical decision task was administered. Among a
      total of 320 words and 140 non-words, 200 words were repeated, while the
      remaining 120 words and the 140 non-words were not repeated. For explicit memory,
      a continuous recognition task was administered, in which 280 words were repeated
      and 100 were not repeated. On the recognition task, both the controls and OCD
      patients showed more positivity to the old words than to the new words during the
      200-600 ms period post-stimulus. Both groups showed faster response time to the
      old words than to the new words. On the lexical decision task, the controls
      showed the old/new effect during the 200-500 ms period post-stimulus, while the
      OCD patients did not. However, OCD patient showed faster response time to the old
      words than to the new words, although OCD patients showed prolonged response
      times to the old words compared to the controls. These results indicate that OCD
      patients have preserved explicit and implicit memory. The absence of old/new
      effect on ERP in OCD patients was discussed in terms of dysfunction of
      frontostriatal system, which plays an important role in both OCD and implicit
      memory.

PMID- 16083911
TI  - Functionally relevant measures of spatial complexity in neuronal dendritic
      arbors.
AB  - We introduce a set of scaling exponents for characterizing global 3D morphologic
      properties of mass distribution, branching and taper in neuronal dendritic
      arbors, capable of distinguishing functionally relevant changes in dendritic
      complexity that standard Sholl analysis and fractal analysis cannot. We
      demonstrate that the scaling exponent for mass distribution, d(M), comprises a
      sum of independent scaling exponents for branching, d(N), and taper, d(T). The
      accuracy of experimental measurements of the scaling exponents was verified using
      computer generated self-similar binary trees of known fractal dimension, and with
      prescribed amounts of branching and taper. The theory was applied to measuring 3D
      spatial complexity in the apical and basal dendritic trees of two functionally
      distinct types of macaque monkey neocortical pyramidal neurons: long
      corticocortical projection neurons from superior temporal cortex to area 46 of
      the prefrontal cortex (PFC), and local projection neurons within area 46 of the
      PFC. Two distinct scaling subregions (proximal and medial) were identified in
      both apical and basal trees of the two neuron types, and scaling exponents were
      fitted. A small but significant difference in mass scaling in the proximal region
      distinguished long from local projection neurons. Interestingly, both classes of
      neuron exhibited a homeostatic pattern of mass distribution across the two
      regions: despite large differences between proximal and medial regions in
      branching and tapering exponents, these effects were compensatory, resulting in a
      uniform, slow reduction of mass with distance from the soma, over both scaling
      regions of the apical and basal trees. Given a uniformly excitable membrane, the
      electrotonic properties of dendritic arbors depend entirely upon mass
      distribution, and its relative contributions from dendritic branching and taper.
      By capturing each of these complex morphologic properties in a single, globally
      descriptive parameter, the new 3D scaling exponents introduced in this study
      permit efficient morphometric characterization of complex dendritic arbors in the
      fewest possible parameters, that can be directly related to their electrotonic
      properties, and hence to neuronal function.

PMID- 16083912
TI  - Single-neuron theory of consciousness.
AB  - By most accounts, the mind arises from the integrated activity of large
      populations of neurons distributed across multiple brain regions. A contrasting
      model is presented in the present paper that places the mind/brain interface not
      at the whole brain level but at the level of single neurons. Specifically, it is
      proposed that each neuron in the nervous system is independently conscious, with
      conscious content corresponding to the spatial pattern of a portion of that
      neuron's dendritic electrical activity. For most neurons, such as those in the
      hypothalamus or posterior sensory cortices, the conscious activity would be
      assumed to be simple and unable to directly affect the organism's macroscopic
      conscious behavior. For a subpopulation of layer 5 pyramidal neurons in the
      lateral prefrontal cortices, however, an arrangement is proposed to be present
      such that, at any given moment: (i) the spatial pattern of electrical activity in
      a portion of the dendritic tree of each neuron in the subpopulation individually
      manifests a complexity and diversity sufficient to account for the complexity and
      diversity of conscious experience; (ii) the dendritic trees of the neurons in the
      subpopulation all contain similar spatial electrical patterns; (iii) the spatial
      electrical pattern in the dendritic tree of each neuron interacts non-linearly
      with the remaining ambient dendritic electrical activity to determine the
      neuron's overall axonal response; (iv) the dendritic spatial pattern is
      reexpressed at the population level by the spatial pattern exhibited by a
      synchronously firing subgroup of the conscious neurons, thereby providing a
      mechanism by which conscious activity at the neuronal level can influence overall
      behavior. The resulting scheme is one in which conscious behavior appears to be
      the product of a single macroscopic mind, but is actually the integrated output
      of a chorus of minds, each associated with a different neuron.

PMID- 16083913
TI  - Acoustical dead zones and the spatial aggregation of whale strandings.
AB  - Cetacean strandings display a marked geographical clustering. We propose a
      simple, two-dimensional ray-dynamics model of cetacean echolocation to examine
      the role played by coastline topography in influencing the location and
      clustering of stranding sites. We find that a number of coastlines known to
      attract cetacean strandings produce acoustical "Dead Zones" where echolocation
      signals are severely distorted by purely geometric effects. Using available
      cetacean stranding data bases from four disparate areas, we show that the
      geographical clusters in the observations correlate strongly with the regions of
      distorted echolocation signals as predicted by the model.

PMID- 16083914
TI  - Assessing the suitability of OSPAR EcoQOs for eutrophication vs ICES criteria for
      England and Wales.
AB  - This paper provides a preliminary evaluation of the suitability of OSPAR
      Ecological Quality objectives for eutrophication for coastal and offshore waters
      of England and Wales on the basis of ICES criteria. In principle, EcoQOs are easy
      to understand, but responses to nutrient enrichment are complex. Few studies
      provide unequivocal evidence of links between inputs and response. Monitoring is
      generally feasible and in place, but needs to be improved. The best EcoQO is
      winter nutrient concentrations. Chlorophyll concentrations are a good indicator
      in environments susceptible to nutrient enrichment. The EcoQO for zoobenthos/fish
      kills potentially meets all criteria for a good indicator; EcoQOs for
      phytoplankton indicator species, oxygen concentrations and zoobenthos changes do
      not. Greater emphasis needs to be placed on seasonal effects of nutrient inputs
      and phytoplankton response, natural susceptibility of different water bodies,
      differences between coastal and offshore environments, and developing longer time
      series of data.

PMID- 16083915
TI  - Moderate acute intake of de-alcoholized red wine, but not alcohol, is protective
      against radiation-induced DNA damage ex vivo -- results of a comparative in vivo
      intervention study in younger men.
AB  - Moderate intake of wine is associated with reduced risk of cardiovascular disease
      and possibly cancer however it remains unclear whether the potential health
      benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine.
      We therefore tested the hypothesis that the non-alcoholic fraction of wine
      protects against genome damage induced by oxidative stress in a crossover
      intervention study involving six young adult males aged 21-26 years. The
      participants adhered to a low plant phenolic compound diet for 48 h prior to
      consuming 300 mL of complete red wine, de-alcoholized red wine or ethanol on
      separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h
      after beverage consumption. Baseline and radiation-induced genome damage was
      measured using the cytokinesis-block micronucleus assay and total plasma catechin
      concentration was measured. Consumption of de-alcoholized red wine significantly
      decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by
      20%. In contrast alcohol tended to increase radiation-induced genome damage and
      complete wine protected against radiation-induced genome damage relative to
      alcohol. The observed effects were only weakly correlated with the concentration
      of total plasma catechin (R=-0.23). These preliminary data suggest that only the
      non-alcoholic fraction of red wine protects DNA from oxidative damage but this
      effect cannot be explained solely by plasma catechin.

PMID- 16083916
TI  - Prevention of human cancer by modulation of chronic inflammatory processes.
AB  - Chronic inflammation induced by biological, chemical and physical factors has
      been associated with increased risk of human cancer at various sites.
      Inflammation facilitates the initiation of normal cells and their growth and
      progression to malignancy through production of pro-inflammatory cytokines and
      diverse reactive oxygen and nitrogen species. These also activate signaling
      molecules involved in inflammation and carcinogenesis such as nuclear
      transcription factor (NF-kappaB), inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2). Several chemopreventive agents act through inhibition
      of signaling pathways (e.g. NF-kappaB), inhibition of oxidant-generating enzymes
      (e.g. iNOS) and mediators of inflammation (e.g. COX-2), scavenging reactive
      oxygen and nitrogen species, and modulation of xenobiotic-metabolizing enzymes
      (especially phase II enzyme induction). Some anti-inflammatory drugs have been
      tested in clinical trials to prevent human cancer at several sites. Better
      understanding of the molecular mechanisms by which chronic inflammation increases
      cancer risk will lead to further development of new strategies for cancer
      prevention at many sites.

PMID- 16083917
TI  - Development of cancer chemopreventive drugs based on mechanistic approaches.
AB  - One of the most important medical practices of the 21st century is the
      chemoprevention of cancer. Much progress has been made in this new emerging
      field, but much work remains before widespread use and practice of cancer
      prevention becomes commonplace. Cancer chemoprevention includes the concepts of
      inhibition, reversal, and retardation of the cancer process. The process of
      carcinogenesis requires 20-40 years to reach invasive cancer. This process
      follows multiple, diverse, and complex pathways in a stochastic process, called
      clonal evolution. Many of these pathways appear amenable to inhibition, reversal,
      or retardation at various points. It is urgent that we identify key pathways in
      the evolution of the cancer cell, which can be exploited to prevent this
      carcinogenesis process. Basic researchers are identifying many genetic lesions
      and epigenetic processes associated with the progression of precancer to invasive
      disease. These precancer lesions are also called intraepithelial neoplasia (IEN).
      Many of these early precancerous lesions favor cell division over quiescence and
      protect cells against apoptosis when signals are present. Many oncogenes, which
      are active during early development, are reactivated in adulthood by aberrant
      gene promoting errors. Normal regulatory genes can become mutated, making them
      insensitive to normal regulatory signals. Tumor suppressor genes are deleted or
      mutated rendering them inactive. These are several of a wide range of defects in
      cellular machinery, which can lead to evolution of the cancer phenotype. Errors
      may not have to appear in a defined order for cells to progress along the cancer
      pathway. To conquer this diverse disease, it is necessary to attack multiple key
      pathways at once for a predetermined period of time. Agent combination prevention
      strategies are, therefore, essential to decrease cancer morbidity. Each cancer
      type, organ location, or individual genetic background may require a custom
      combination of prevention strategies to be successful.

PMID- 16083918
TI  - Modulation of xenobiotic metabolising enzymes by anticarcinogens -- focus on
      glutathione S-transferases and their role as targets of dietary chemoprevention
      in colorectal carcinogenesis.
AB  - There is evidence that consumption of certain dietary ingredients may favourably
      modulate biotransformation of carcinogens. Associated with this is the hypothesis
      that the risk for developing colorectal cancer could be reduced, since its
      incidence is related to diet. Two main groups of biotransformation enzymes
      metabolize carcinogens, namely Phase I enzymes, which convert hydrophobic
      compounds to more water-soluble moieties, and Phase II enzymes (e.g. glutathione
      S-transferases [GST]), which primarily catalyze conjugation reactions. The
      conjugation of electrophilic Phase I intermediates with glutathione, for
      instance, frequently results in detoxification. Several possible colon
      carcinogens may serve as substrates for GST isoenzymes that can have marked
      substrate specificity. The conjugated products could be less toxic/genotoxic if
      GSTs are induced, thereby reducing exposure. Thus, numerous studies have shown
      that the induction of GSTs by antioxidants enables experimental animals to
      tolerate exposure to carcinogens. One important mechanism of GST induction
      involves an antioxidant-responsive response element (ARE) and the transcription
      factor nuclear factor E2-related factor 2 (Nrf2), which is bound to the Kelch
      like ECH associated protein 1 (Keap1) in the cytoplasm. Antioxidants may disrupt
      the Keap-Nrf2 complex, allowing Nrf2 to translocate to the nucleus and mediate
      expression of Phase II genes via interaction with the ARE. GSTs are also induced
      by butyrate, a product of gut flora-derived fermentation of plant foods, which
      may act via different mechanisms, e.g. by increasing histone acetylation. GSTs
      are expressed with high inter-individual variability in human colonocytes, which
      points to large differences in cellular susceptibility to xenobiotics. Enhancing
      expression of GSTs in human colon tissue could therefore contribute to reducing
      cancer risks. However, it has not been demonstrated in humans that this mechanism
      is associated with cancer prevention. In the future, it will be useful to
      determine GSTs during dietary intervention studies to enhance our understanding
      of this protective mechanism.

PMID- 16083919
TI  - Selective estrogen receptor modulators (SERMs): mechanisms of anticarcinogenesis
      and drug resistance.
AB  - Despite the beneficial effects of estrogens in women's health, there is a
      plethora of evidence that suggest an important role for these hormones,
      particularly 17beta-estradiol (E(2)), in the development and progression of
      breast cancer. Most estrogenic responses are mediated by estrogen receptors
      (ERs), either ERalpha or ERbeta, which are members of the nuclear receptor
      superfamily of ligand-dependent transcription factors. Selective estrogen
      receptor modulators (SERMs) are ER ligands that in some tissues (i.e. bone and
      cardiovascular system) act like estrogens but block estrogen action in others.
      Tamoxifen is the first SERM that has been successfully tested for the prevention
      of breast cancer in high-risk women and is currently approved for the endocrine
      treatment of all stages of ER-positive breast cancer. Raloxifene, a newer SERM
      originally developed for osteoporosis, also appears to have preventive effect on
      breast cancer incidence. Numerous studies have examined the molecular mechanisms
      for the tissue selective action of SERMs, and collectively they indicate that
      different ER ligands induce distinct conformational changes in the receptor that
      influence its ability to interact with coregulatory proteins (i.e. coactivators
      and corepressors) critical for the regulation of target gene transcription. The
      relative expression of coactivators and corepressors, and the nature of the ER
      and its target gene promoter also affect SERM biocharacter. This review
      summarizes the therapeutic application of SERMs in medicine; particularly breast
      cancer, and highlights the emerging understanding of the mechanism of action of
      SERMs in select target tissues, and the inevitable development of resistance.

PMID- 16083920
TI  - Modulation of multigene expression and proteome profiles by chemopreventive
      agents.
AB  - Analysis of transcriptome and proteome profiles by microarray technologies
      provides a formidable, new tool in cancer chemoprevention research. An ideal
      chemopreventive agent should not excessively alter per se the basal make-up of
      multigene expression and protein synthesis and should at the same time be able to
      attenuate alterations induced by risk factors. In order to validate this working
      hypothesis, we previously performed a series of studies in animal models using
      the thiol N-acetyl-l-cysteine (NAC) and the nonsteroidal antiinflammatory drug
      sulindac. We report herein the results of new studies evaluating modulation of
      DNA adduct levels and expression of 4858 genes in lung and liver of Sprague
      Dawley rats, either unexposed or exposed to environmental cigarette smoke (ECS).
      The tested chemopreventive agents included NAC, oltipraz (OPZ), 5,6-benzoflavone
      (5,6-BF), phenethyl isothiocyanate (PEITC), and indole 3-carbinol (I3C).
      Combinations of OPZ with NAC and of PEITC with I3C were also assayed. Excepting
      OPZ, all treatments inhibited by at least 50% the formation of bulky DNA adducts
      in the lung of ECS-exposed rats. Hierarchical cluster analysis and principal
      component analysis allowed us to classify the agents according to their influence
      on basal gene expression and their ability to attenuate ECS-induced transcriptome
      alterations. PEITC and I3C were the most effective but the least safe agents. 5,6
      BF displayed intermediate patterns. OPZ was poorly effective in lung and
      considerably altered the basal gene expression in liver. NAC had a medium
      efficacy and was the safest agent, as also supported by the analysis of 518
      proteins in rat lung.

PMID- 16083921
TI  - Age and medication effects on rhythmic responses in ADHD: possible oscillatory
      mechanisms?
AB  - Voluntary motor responses in children with attention-deficit hyperactivity
      disorder (ADHD) may reflect underlying neuronal oscillatory mechanisms. The aims
      of this study were: (1) to corroborate the presence of rhythmic motor
      abnormalities on tapping test in children with attention-deficit hyperactivity
      disorder, shown in previous studies; (2) to delineate the characteristics of ADHD
      children demonstrating these rhythmic abnormalities; (3) to assess the impact of
      methylphenidate (Ritalin) on this abnormal motor phenomenon. The study was
      designed in a double blind manner. Sixty-four ADHD children aged 6-12 years and
      60 matched controls underwent a finger tapping test (1-5 Hz). We measured the
      abnormal rhythmic tapping with and without methylphenidate treatment in a double
      blind design. Conventional statistical analysis was used to assess the
      correlation of the presence of motor abnormality with various clinical
      characteristics (such as degree of hyperactivity/impulsivity). Fifty-six percent
      of children with ADHD compared to 8% of controls demonstrated abnormal rhythmic
      responses at a mean frequency of 3.1+/-0.9 Hz. These erroneous voluntary
      movements were more common in children with a greater degree of hyperactivity, in
      younger children but not significantly altered by methylphenidate treatment.
      Surprisingly, abnormal rhythmic responses showed less variability than found for
      responses for which the tapping was adequately paced, suggesting different motor
      control processes for normal and abnormal paced tapping. We speculate that
      rhythmic tapping responses reflect abnormal oscillatory mechanisms involved in
      ADHD, exacerbated in younger children with ADHD and in those in whom the
      hyperactivity/impulsivity is more pronounced.

PMID- 16083922
TI  - Effects of long-term continuous exposure to light on memory and anxiety in mice.
AB  - The studies on the relationship between the light/dark cycle and memory function
      mostly used protocols of acute disruption of the circadian rhythm. The aim of the
      present study is to verify the effects of long-term continuous exposure to light
      on memory, anxiety and motor parameters of mice tested in the plus-maze
      discriminative avoidance task. Mice were conditioned to choose between the two
      enclosed arms (one aversive and one non-aversive) while avoiding the open arms of
      a modified elevated plus-maze apparatus. Memory was evaluated by the time spent
      in the aversive enclosed arm, anxiety was evaluated by the time spent in the open
      arms and locomotor behavior was evaluated by number of entries in the arms of the
      maze. The results showed that long-term (35-42 days) continuous light exposure
      did not modify memory or anxiety parameters but increased locomotor activity.
      While the increase in locomotor behavior is in line with previous studies, the
      unexpected absence of alterations in memory and anxiety (reported to be
      influenced by the circadian rhythm) is discussed.

PMID- 16083923
TI  - Drinking spout orifice size affects licking behavior in inbred mice.
AB  - Using a lickometer, we assessed the effect of drinking spout orifice size on the
      licking behavior of inbred mice [C57BL/6J, SWR/J, 129P3/J and DBA/2J]. Animals
      licked from drinking spout sipper tubes that had what were defined as either a
      large (2.7 mm) or a small (1.5 mm) orifice. Mice took approximately twice as many
      licks from a stationary single small orifice drinking spout than when licking
      from a spout with a large orifice during separate 30-min sessions. However, their
      total intake volume was approximately the same. We calculated that mice received
      a mean of 0.55 muL per lick from the drinking tubes with a small orifice and a
      mean of 1.15 muL per lick from the drinking tubes with a large orifice. Thus, the
      animals appear to have regulated their fluid intake by proportionally adjusting
      their licking as a function of the lick volume. On average, this regulation
      occurred through modulation of the size of licking bursts and not their
      frequency. However, strain differences in compensation strategy were observed.
      When licking was restricted to a series of 5-s trials in a 30-min brief access
      test session, the smaller orifice size increased the range of responsiveness that
      was expressed. Mice increased their average licks per trial by 20% and took 60%
      more trials when licking from a spout with a small orifice. Interestingly, when
      the orifice size was quasi-randomly varied within a brief access session, licking
      was greater from large orifice drinking spouts, suggesting that water delivered
      from the two orifice sizes differs in its reinforcement efficacy. These findings
      demonstrate that drinking spout orifice size can significantly influence
      experimental outcomes in licking tests involving mice and care should be taken in
      controlling this variable in testing the effects of taste or other factors on
      ingestive behavior.

PMID- 16083924
TI  - Bangangxanthone A and B, two xanthones from the stem bark of Garcinia polyantha
      Oliv.
AB  - Two xanthones, bangangxanthone A (1) [1,5,8-trihydroxy-6'-methyl-6'-(4-methylpent
      3-enyl)- pyrano[2',3':3,4]xanthone] and B (2) [1,4,8-trihydroxy-2
      prenylxanthone], along with two known xanthones, 1,5-dihydroxyxanthone, 2-hydroxy
      1,7-dimethoxyxanthone and the pentacyclic triterpenoids, friedelin, oleanolic
      acid and lupeol were isolated from the chloroform extract of the stem bark of
      Garcinia polyantha. The structures of these compounds were assigned by
      spectroscopic analysis. Compounds 1-4 showed antioxidant DPPH radical scavenging
      activities.

PMID- 16083925
TI  - Antimicrobial biflavonoids from the aerial parts of Ouratea sulcata.
AB  - Investigation of the aerial parts of Ouratea sulcata led to the isolation of a
      biflavonoid named sulcatone A, together with the known compounds, 3-hydroxy-2,3
      dihydroapigenyl-[I-4',O,II-3']-dihydrokaempferol, amentoflavone, lophirone A,
      agathisflavone, stigmasterol and stigmasteryl-3-O-beta-D-glucopyranoside. The
      structure of the compound was assigned as apigenyl-[I-4',O,II-3']
      dihydrokaempferol, by means of spectroscopic analysis. Sulcatone A and 3-hydroxy
      2,3-dihydroapigenyl-[I-4',O,II-3']-dihydrokaempferol exhibited significant in
      vitro antimicrobial activities against a range of microorganisms.

PMID- 16083926
TI  - Cloning and functional characterisation of a cis-muuroladiene synthase from black
      peppermint (Menthaxpiperita) and direct evidence for a chemotype unable to
      synthesise farnesene.
AB  - Using oligonucleotide primers designed to the known gene sequence of an (E)-beta
      farnesene (EbetaF) synthase, two cDNA sequences (MxpSS1 and MxpSS2) were cloned
      from a black peppermint (Menthaxpiperita) plant. MxpSS1 encoded a protein with
      96% overall amino acid sequence identity with the EbetaF synthase. Recombinant
      MxpSS1 produced in Escherichia coli, after removal of an N-terminal thioredoxin
      fusion, had a K(m) for FPP of 1.91+/-0.1 microM and k(cat) of 0.18 s(-1), and
      converted farnesyl diphosphate (FPP) into four products, the major two being cis
      muurola-3,5-diene (45%) and cis-muurola-4(14),5-diene (43%). This is the first
      cis-muuroladiene synthase, to be characterised. MxpSS2 encoded a protein with
      only two amino acids differing from EbetaF synthase. Recombinant MxpSS2 protein
      showed no activity towards FPP. One of the two mutations, at position 531
      (leucine in MxpSS2 and serine in EbetaF synthase) was shown, by structural
      modelling to occur in the J-K loop, an element of the structure of sesquiterpene
      synthases known to be important in the reaction mechanism. Reintroduction of the
      serine at position 531 into MxpSS2 by site-directed mutagenesis restored EbetaF
      synthase activity (K(m) for FPP 0.98+/-0.12 microM, k(cat) 0.1 s(-1)),
      demonstrating the crucial role of this residue in the enzyme activity. Analysis,
      by GC-MS, of the sesquiterpene profile of the plant used for the cloning,
      revealed that EbetaF was not present, confirming that this particular mint
      chemotype had lost EbetaF synthase activity due to the observed mutations.

PMID- 16083927
TI  - Who calls QUIT? The characteristics of smokers seeking advice via a telephone
      helpline compared with smokers attending a clinic and those in the general
      population.
AB  - OBJECTIVE: To compare the characteristics of callers to a telephone helpline with
      those of smokers seeking assistance through a clinic and smokers in a general
      population sample. STUDY DESIGN: Data were gathered from callers to the Quitline
      in May and June 2000. Screening data were used for smokers attending the South
      London & Maudsley NHS Smokers' Clinic from May 2000 to April 2001. The results of
      the 2000/2001 General Household Survey (GHS) were used to estimate the
      characteristics of smokers in the general population. METHODS: Callers to the
      Quitline (n=1162) surveyed during the summer of 2000, smokers attending the
      Maudsley Hospital Smokers' Clinic between May 2000 and April 2001 (n=1127), and
      smokers surveyed in the GHS between April 2000 and March 2001 (n=14,089) were
      compared on demographic characteristics, tobacco dependence and readiness to
      quit. RESULTS: Women and older smokers are more likely to seek help, but the
      Quitline attracts more calls from younger smokers. The age profile of helpline
      callers corresponds more closely to that of the general population of smokers
      than does the age profile of clinic attenders. Quitline callers are more
      dependent than the general population of smokers; clinic attenders are even more
      dependent. In comparison with the general population, the majority of Quitline
      callers have plans to quit smoking soon or have already stopped smoking.
      CONCLUSIONS: Telephone helplines reach a more representative sample of smokers in
      various states of readiness to quit, and provide a service for a population not
      reached by clinics.

PMID- 16083928
TI  - New cases of diabetes mellitus in England and Wales, 1994-1998: database study.
AB  - OBJECTIVE: The objective of this study was to estimate the annual rate of
      diagnosis of new cases of diabetes mellitus in England and Wales, and the number
      of new cases in each year. STUDY DESIGN: Cohort study. METHOD: Analysis of
      electronic patient records from the General Practice Research Database, using 208
      general practices with a total list size of 1.3 million patients. RESULTS: We
      estimate that the national rate of diagnosis of new cases of diabetes in England
      and Wales was 17.5 [95% confidence intervals (CI) 16.6--18.4] per 10,000 person
      years in 1994 and 22.1 (95%CI 21.2--23.0) per 10,000 person-years in 1998. We
      estimate that there were 87,642 new cases of diabetes mellitus in England and
      Wales in 1994 and 111,345 in 1998. CONCLUSIONS: We estimate that the rate at
      which new cases of diabetes were diagnosed rose by about 26% in England and Wales
      from 1994 to 1998. This conclusion was unchanged when we took account of the
      ageing of the national populations between the beginning and end of the study
      period. We estimate that the number of new cases of diabetes diagnosed each year
      in England and Wales also increased by one-quarter over the same period. If the
      number of cases and the rate at which they are diagnosed continues to increase,
      this will need to be considered by those planning services for people with
      diabetes.

PMID- 16083929
TI  - Prevalence of sleepiness in a group of Brazilian lorry drivers.
AB  - OBJECTIVE: To determine the prevalence of sleepiness in a group of Brazilian
      lorry drivers. STUDY DESIGN: Cross-sectional study. METHODS: This study used a
      self-administrated questionnaire and the Epworth Sleepiness Scale (ESS). The
      questionnaire included questions regarding demographic features, professional
      data, sleep habits, night-time symptoms, excessive daytime sleepiness and history
      of previous automobile accidents. RESULTS: Four hundred and thirty-eight male
      drivers, aged 34.2+/-9.5 years (mean+/-SD), were included in the study. The mean
      number of hours spent driving each day was 9.2+/-2.6h, compared with 4.5+/-2.3h
      for the night shift. The median distance covered weekly was 1,200 km (range 70
      6,000 km). The most common sleep complaints were insomnia (26.6%), loud snoring
      (45%) and witnessed apnoea (7.6%). Eighty-six of 392 (22%) drivers reported
      falling asleep while driving, and 11 (2.8%) subjects indicated falling asleep
      daily or almost daily. One hundred and seventy-one drivers (39%) had been
      involved in a traffic accident, and 21 of 128 drivers (16.4%) indicated
      sleepiness as a possible contributing factor. The ESS was higher than 10 points
      in 120 (28%) of the interviewees. CONCLUSIONS: Sleepiness is a prevailing symptom
      in lorry drivers and is probably related to accidents.

PMID- 16083930
TI  - Milk amyloid A: correlation with cellular indices of mammary inflammation in cows
      with normal and raised serum amyloid A.
AB  - This study compared concentrations of amyloid A in bovine milk with the cell
      based indicators of intramammary inflammation, somatic cell count and California
      Mastitis Test. Mammary quarter data pertaining to 180 cows were categorised
      according to concentrations of serum amyloid A in the cow of origin. Ranked
      correlation, ranked regression and receiver operator characteristics all
      demonstrated acceptable agreement between milk amyloid A concentrations and cell
      based indices. There were some indications of reduction in this agreement, in
      cows with raised concentrations of serum amyloid A. However, there were also
      indications that serum amyloid A did not significantly influence milk amyloid A.
      The results of the current study indicate that milk amyloid A exhibits good
      correlation with established cell-based indicators of intramammary inflammation.

PMID- 16083931
TI  - Non-destructive testing of ceramic balls using high frequency ultrasonic
      resonance spectroscopy.
AB  - Although ceramic balls are used more and more for bearings in the aerospace and
      space industries, defects in this type of ceramic material could be dangerous,
      particularly if such defects are located close to the surface. In this paper, we
      propose a non-destructive testing method for silicon nitride balls, based on
      ultrasonic resonance spectroscopy. Through the theoretical study of their elastic
      vibrations, it is possible to characterize the balls using a vibration mode that
      is similar to surface wave propagation. The proposed methodology can both excite
      spheroidal vibrations in the ceramic balls and detect such vibrations over a
      large frequency range. Studying their resonance spectrums allows the balls'
      elastic parameters be characterized. Ours is an original method that can quickly
      estimate the velocity of surface waves using high frequency resonances, which
      permits surface and sub-surface areas to be tested specifically. Two applications
      are described in this paper. Both use velocity measurements to achieve their
      different goals, the first to differentiate between flawless balls from different
      manufacturing processes, and the second to detect small defects, such as cracks.
      Our method is rapid and permits the entire ceramic ball to be tested in an
      industrial context.

PMID- 16083932
TI  - RNA interference against enterovirus 71 infection.
AB  - Enterovirus 71 (EV71) is a highly infectious major causative agent of hand, foot,
      and mouth disease (HFMD) which could lead to severe neurological complications.
      There is currently no effective therapy against EV71. In this study, RNA
      interference (RNAi) is employed as a therapeutic approach for specific viral
      inhibition. Various regions of the EV71 genome were targeted for inhibition by
      chemically synthesized siRNAs. Transfection of rhabdomyosarcoma (RD) cells with
      siRNA targeting the 3'UTR, 2C, 3C, or 3D region significantly alleviated
      cytopathic effects of EV71. The inhibitory effect was dosage-dependent with a
      corresponding decrease in viral RNA, viral proteins, and plaque formations by
      EV71. Viral inhibition of siRNA transfected RD cells was still evident after 48
      h. In addition, no significant adverse off-target silencing effects were
      observed. These results demonstrated the potential and feasibility for the use of
      siRNA as an antiviral therapy for EV71 infections.

PMID- 16083933
TI  - Heterologous RNA replication enhancer stimulates in vitro RNA synthesis and
      template-switching by the carmovirus, but not by the tombusvirus, RNA-dependent
      RNA polymerase: implication for modular evolution of RNA viruses.
AB  - The viral RNA plays multiple roles during replication of RNA viruses, serving as
      a template for complementary RNA synthesis and facilitating the assembly of the
      viral replicase complex. These roles are coordinated by cis-acting regulatory
      elements, such as promoters and replication enhancers (REN). To test if these RNA
      elements can be used by related viral RNA-dependent RNA polymerases (RdRp), we
      compared the potential stimulatory effects of homologous and heterologous REN
      elements on complementary RNA synthesis and template-switching by the tombus-
      (Cucumber necrosis virus, CNV), carmovirus (Turnip crinkle virus, TCV) and
      hepatitis C virus (HCV) RdRps in vitro. The CNV RdRp selectively utilized its
      cognate REN, while discriminating against the heterologous TCV REN. On the
      contrary, RNA synthesis by the TCV RdRp was stimulated by the TCV REN and the
      heterologous tombusvirus REN with comparable efficiency. The heterologous REN
      elements also promoted in vitro template-switching by the TCV and HCV RdRps.
      Based on these observations, we propose that REN elements could facilitate
      intervirus recombination and post-recombinational amplification of new
      recombinant viruses.

PMID- 16083934
TI  - Physical and immunological characterization of a recombinant secreted form of the
      membrane protein encoded by the vaccinia virus L1R gene.
AB  - We reported that immunization with recombinant proteins derived from vaccinia
      virus (VV) particles could provide protection against infection. Here we describe
      the physical and antigenic properties of the L1R membrane protein. The
      recombinant protein (L1R(185t)) was secreted as a monomer and correct folding was
      suggested by the presence of three intramolecular disulfide bonds and binding to
      conformation-specific monoclonal antibodies (MAbs). Furthermore, anti-L1R(185t)
      rabbit antisera exhibited potent virus-neutralizing activity against the IMV form
      of VV. We raised six MAbs against L1R(185t). Three recognized linear epitopes
      (residues 118--128) and neutralized IMV infectivity. These MAbs blocked binding
      of each other to L1R(185t) but failed to block binding of two previously
      described neutralizing anti-L1R MAbs, 7D11 and 2D5. The latter two antibodies
      blocked each other in binding L1R(185t). Thus, two antigenic sites on L1R overlap
      functional domains and based on recent structural studies these are found in
      accessible regions of the IMV L1R protein.

PMID- 16083935
TI  - Sequence motif upstream of the Hendra virus fusion protein cleavage site is not
      sufficient to promote efficient proteolytic processing.
AB  - The Hendra virus fusion (HeV F) protein is synthesized as a precursor, F(0), and
      proteolytically cleaved into the mature F(1) and F(2) heterodimer, following an
      HDLVDGVK(109) motif. This cleavage event is required for fusogenic activity. To
      determine the amino acid requirements for processing of the HeV F protein, we
      constructed multiple mutants. Individual and simultaneous alanine substitutions
      of the eight residues immediately upstream of the cleavage site did not eliminate
      processing. A chimeric SV5 F protein in which the furin site was substituted for
      the VDGVK(109) motif of the HeV F protein was not processed but was expressed on
      the cell surface. Another chimeric SV5 F protein containing the HDLVDGVK(109)
      motif of the HeV F protein underwent partial cleavage. These data indicate that
      the upstream region can play a role in protease recognition, but is neither
      absolutely required nor sufficient for efficient processing of the HeV F protein.

PMID- 16083936
TI  - Motion-onset VEPs reflect long maturation and early aging of visual motion
      processing system.
AB  - Pattern-reversal and motion-onset visual evoked potentials (VEPs) were
      simultaneously tested in a group of 70 healthy subjects between the ages of 6-60
      years to verify suspected differences in maturation and aging dynamics of the
      pattern and motion processing subsystems of the visual pathway. The motion-onset
      VEPs displayed dramatic configuration development and shortening of latencies up
      to 18 years of age (correl. coeff. -0.85; p < 0.001) and systematic prolongation
      from about 20 years of age (correl. coeff. 0.70; p < 0.001). This confirms long
      lasting maturation of the magnocellular system and/or motion processing cortex
      and their early age related changes. Less significant changes of pattern-reversal
      VEPs in the tested age range can be interpreted as a sign of early maturation of
      the parvocellular system and its enhanced functional endurance in the elderly.

PMID- 16083937
TI  - Reliability of parameter estimation in respirometric models.
AB  - When modelling a biochemical system, the fact that model parameters cannot be
      estimated exactly stimulates the definition of tests for checking unreliable
      estimates and design better experiments. The method applied in this paper is a
      further development from Marsili-Libelli et al. [2003. Confidence regions of
      estimated parameters for ecological systems. Ecol. Model. 165, 127-146.] and is
      based on the confidence regions computed with the Fisher or the Hessian matrix.
      It detects the influence of the curvature, representing the distortion of the
      model response due to its nonlinear structure. If the test is passed then the
      estimation can be considered reliable, in the sense that the optimisation search
      has reached a point on the error surface where the effect of nonlinearities is
      negligible. The test is used here for an assessment of respirometric model
      calibration, i.e. checking the experimental design and estimation reliability,
      with an application to real-life data in the ASM context. Only dissolved oxygen
      measurements have been considered, because this is a very popular experimental
      set-up in wastewater modelling. The estimation of a two-step nitrification model
      using batch respirometric data is considered, showing that the initial amount of
      ammonium-N and the number of data play a crucial role in obtaining reliable
      estimates. From this basic application other results are derived, such as the
      estimation of the combined yield factor and of the second step parameters, based
      on a modified kinetics and a specific nitrite experiment. Finally, guidelines for
      designing reliable experiments are provided.

PMID- 16083938
TI  - Leaching of heavy metals and polycyclic aromatic hydrocarbons from reclaimed
      asphalt pavement.
AB  - The work presented herein displays the results of a study addressing
      environmental concerns related to the possible leaching of pollutants from
      reclaimed asphalt pavement. Samples from an experimental site were tested in both
      static batch tests and column leaching tests. Selected heavy metals and
      polycyclic aromatic hydrocarbons (PAHs) were analysed in leachates. The results
      have allowed us to consider the leaching of pollutants to be rather weak for most
      of the parameters studied. Concentrations in solutions from batch leaching tests
      were generally below the EC limit values for drinking water. Pollutant
      concentrations from column experiments were higher in solutions as of the initial
      leaching stages, but then decreased rapidly and wound up at values below the
      detection limits. The factors influencing results proved to be the material grain
      size and the percolation water flow rate. Results from leaching experiments
      performed on core samples taken on two rebuilt road section pavements, containing
      10% and 20% of reclaimed asphalt pavement, respectively, confirmed the results
      obtained from the batch and column experiments.

PMID- 16083939
TI  - Chemical characterisation of PM episodes in NE Spain.
AB  - The chemical composition of ambient particulate matter (PM) varies widely as a
      function of its main emission sources and of the chemical reactions which take
      place in the atmosphere. The aim of this study is to obtain the chemical profile
      of PM10 and PM2.5 during peak PM episodes, thus identifying the main emission
      sources and/or atmospheric processes which originate the PM episodes. To this
      end, cluster analysis was applied to a set of PM10 and PM2.5 data collected
      throughout 2001 in two urban and industrialised areas in NE Spain. As a result of
      this analysis, five clusters were identified for each site, and the
      interpretation of their chemical profiles lead to the identification of five
      types of peak PM episodes for each site: industrial, traffic and regional re
      circulation episodes at both sites, plus crustal episodes in Barcelona, and peak
      traffic and industrial episodes (T+I) in Tarragona. Traffic episodes are
      characterised by daily means of 23 and 10 microg/m3 of OM+EC in Barcelona and
      Tarragona in PM10. Levels of secondary inorganic aerosols reach average daily
      means of 19 and 11 microg/m3 in Barcelona and Tarragona in PM10 during industrial
      episodes. High levels of sulphate (>5 microg/m3) and ozone (up to 77 microg/m3
      daily mean) are good tracers of regional re-circulation episodes. During crustal
      episodes daily means of crustal elements reach up to 34 microg/m3 in Barcelona.
      Special attention has been drawn to the composition of the mineral matter during
      the different PM episodes.

PMID- 16083940
TI  - The effects of elevated CO2 on clonal growth and nutrient content of submerge
      plant Vallisneria spinulosa.
AB  - An approximately four months long glasshouse experiment was conducted to examine
      the effects of elevated carbon dioxide (CO(2)) concentration (1,000 +/- 50
      micromol mol(-1)) in the atmosphere on biomass accumulation and allocation
      pattern, clonal growth and nitrogen (N), phosphorus (P) accumulation by the
      submerged plant Vallisneria spinulosa Yan. Elevated CO(2) significantly increased
      V. spinulosa total fresh biomass ( approximately 130%) after 120 days, due to
      more biomass accumulation in all morphological organs than in those at ambient
      CO(2) (390 +/- 20 micromol mol(-1)). About 75% of the additional total biomass at
      elevated CO(2) was accounted for by leaf and rhizome (above ground) biomass and
      only 25% of it belonged to root and turion (below ground). However, the turions
      biomass exhibited a greater increase rate than that of organ above ground, which
      caused reduction in the above/below ground biomass ratio. The clonal growth of V.
      spinulosa responded positively to elevated CO(2). The number of primary ramets
      increased up to 1.4-folds at elevated CO(2) and induced a dense growth pattern.
      For nutrients absorption, concentration of N in leaf and in turion was
      significantly (p <or= 0.05) reduced by 13.4% and by 15.7% in elevated CO(2) and
      were not affected in both root and rhizome. Percent P, in contrast, was
      significantly (p <or= 0.05) enhanced in all of the organs, ranging from 35% to
      147%, except for turion. Compared with those in ambient CO(2), the mean
      accumulation per ramet of N and P significantly higher in elevated CO(2). These
      results showed that elevated CO(2) could promote submerged plant biomass
      accumulation, and it should be an adaptive strategy for clonal plants to increase
      the nutrient absorption efficiency of root and reproduce more clonal ramets to
      exploit enough resources to match with higher growth in elevated CO(2).

PMID- 16083941
TI  - Experimental in situ chemical peroxidation of atrazine in contaminated soil.
AB  - Lab-scale experiments of in situ chemical oxidation (ISCO), were performed on
      soil contaminated with 100 mg kg(-1) of atrazine (CIET). The oxidant used was
      hydrogen peroxide catalysed by naturally occurring minerals or by soluble Fe(II)
      sulphate, added in aqueous solution. The oxidation conditions were:
      CIET:H2O2=1:1100, 2 PV or 3 PV reaction volume, Fe(II):H2O2=0, 1:22, 1:11.
      Stabilized (with KH2PO4 at a concentration of 16 g l(-1)) or non-stabilized
      hydrogen peroxide was used. The pH of the reagents was adjusted to pH=1 with
      sulphuric acid, or was not altered. Results showed that the addition of soluble
      Fe(II) increased the temperature of the soil slurry and the use of stabilized
      hydrogen peroxide resulted in a lower heat generation. The treatment reduced the
      COD of the soil of about 40%, pH was lowered and natural organic matter became
      less hydrophobic. The highest atrazine conversion (89%) was obtained in the
      conditions: 3 PV, Fe(II):H2O2=1:11 with stabilized hydrogen peroxide added in two
      steps. The stabilizer only increased H2O2 life-time significantly when soluble
      Fe(II) was added. Results indicate as preferential degradation pathway of
      atrazine in soil dechlorination instead of dealkylation.

PMID- 16083942
TI  - Leaching of oryzalin and diuron through undisturbed vineyard soil columns under
      outdoor conditions.
AB  - Field studies monitoring herbicide pollution in the vineyards of Burgundy
      (France) have revealed that drinking water reservoirs are contaminated with
      several pre-emergence herbicides. An assessment of the leaching of two such
      herbicides, diuron and oryzalin, was therefore performed using lysimeters, under
      outdoor conditions, from May 2001 to May 2002. Four vineyard soils from Vosne
      Romanee (Burgundy) were chosen along a topolithosequence: a rendosol and three
      calcosols. After 673 mm of rainfall, greater amounts of diuron than oryzalin were
      measured in percolates: respectively 0.10-0.84% and 0.02-0.43% of applied
      herbicide, depending on soils. Measurements for diuron metabolites detected
      greater amounts of DCPMU than DCPU in the percolates: respectively 0.05-0.13% and
      0-0.04% of the applied diuron. At the end of the monitoring period, more residues
      of diuron than oryzalin were recovered in the soil profiles: respectively 4.6-9%
      and 1.4-4.4%. The oryzalin residues were found mainly in the upper 10 cm of soil
      columns, whereas diuron residues were present in the whole core. The mobility of
      both oryzalin and diuron seems fairly well-related to soil organic carbon
      content; the mobility of diuron is also related to soil texture (sand and coarse
      material contents). Under such experimental conditions, this study confirms that
      diuron leaching, and therefore potential groundwater contamination, is greater
      than that of oryzalin.

PMID- 16083943
TI  - Immobilized humic substances as sorbents.
AB  - A new method was developed for the immobilization of humic substances. Humic
      acids (HA) immobilized onto different carriers were studied as sorbents for
      organic and inorganic substances. The sorption isotherms of 4-aminoazobenzene,
      Crystal Violet, Methylene Green, and flavine mononucleotide on immobilized HA
      show that pH and salt concentration have a significant effect on the sorption
      process, largely depending on the properties of polymeric matrix. Humic acids
      from different sources showed differing sorption capacity for the studied groups
      of substances.

PMID- 16083944
TI  - The influence of EDDS on the uptake of heavy metals in hydroponically grown
      sunflowers.
AB  - Phytoextraction is an environmentally friendly in situ technique for cleaning up
      metal contaminated land. Unfortunately, efficient metal uptake by remediation
      plants is often limited by low phytoavailability of the targeted metals. Chelant
      assisted phytoextraction has been proposed to improve the efficiency of
      phytoextraction. Phytoremediation involves several subsequent steps: transfer of
      metals from the bulk soil to the root surfaces, uptake into the roots and
      translocation to the shoots. Nutrient solution experiments address the latter two
      steps. In this context we investigated the influence of the biodegradable
      chelating agent SS-EDDS on uptake of essential (Cu and Zn) and non-essential (Pb)
      metals by sunflowers from nutrient solution. EDDS was detected in shoots and
      xylem sap for the first time, proving that it is taken up into the above ground
      biomass of plants. The essential metals Cu and Zn were decreased in shoots in the
      presence of EDDS whereas uptake of the non-essential Pb was enhanced. We suggest
      that in the presence of EDDS all three metals were taken up by the non-selective
      apoplastic pathway as the EDDS complexes, whereas in the absence of EDDS
      essential metal uptake was primarily selective along the symplastic pathway. This
      shows that synthetic chelating agents do not necessarily increase uptake of heavy
      metals, when soluble concentrations are equal in the presence and absence of
      chelates.

PMID- 16083945
TI  - Dietary intake of PCDDs, PCDFs and dioxin-like PCBs, due to the consumption of
      various marine organisms from Korea.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs)
      and dioxin-like polychlorinated biphenyls (DL-PCBs) residues were measured in 70
      marine organisms (40 species) from Korean coastal waters. The PCDD/Fs residues in
      the organisms varied from 0.02 to 4.39 pg WHO-TEQ/g wet weight and the DL-PCBs
      residues varied from 0.008 to 6.0 pg WHO-TEQ/g wet weight. The levels in fish
      from Korean coastal waters were comparable to those found in other countries.
      Comparing organism groups, the highest PCDD/Fs and DL-PCBs residues were recorded
      in crustaceans, followed by fish, cephalopods, bivalves and gastropods. Although
      the congener distributions of PCDD/Fs and DL-PCBs in the organism groups were
      different, the dominant contributors to the total TEQ concentrations in all
      groups were 2,3,4,7,8-pentachlorinated dibenzofuran (PeCDF), 1,2,3,7,8
      pentachlorinated dibenzo-p-dioxin (PeCDD) and PCB 126. The dietary intake of
      PCDD/Fs and DL-PCBs from the consumption of marine organisms in Korea was
      estimated to be 0.68 pg WHO-TEQ/kg bodyweight/day. The contribution of DL-PCBs to
      the total dietary intake from all organisms groups averaged 60%. The relative
      contribution of each organism group to the total dietary intake was, in
      descending order: fish, crustaceans, cephalopods, bivalves and gastropods. The
      current dietary intake was lower than those in countries with a similar dietary
      pattern to Korea, but higher than those in countries with smaller quantities of
      seafood consumption.

PMID- 16083946
TI  - Seasonal pollution characteristics of organic compounds in atmospheric fine
      particles in Beijing.
AB  - Beijing is a rapidly developing city with severe and unique air pollution
      problems. Organic matter is the most abundant fraction in fine particles in
      Beijing, occupying 30-50% of the total mass, indicating its key role in air
      pollution control. However, detailed chemical characterization of particulate
      organic matter in Beijing has never been reported. In this study, fine particles
      in the urban atmosphere in Beijing were investigated for its organic components
      by GC/MS technique. Over 100 individual organic compounds were identified and
      quantified in 25 PM2.5 samples from the summer, autumn and winter of 2002-2003.
      Alkanes, fatty acids, dicarboxylic acids, polycyclic aromatic hydrocarbons and
      some important tracer compounds (hopanes, levoglucosan and steroids) were the
      major constituents with the sum of their concentrations of 502, 1471 and 1403 ng
      m(-3) in summer, autumn and winter, respectively. Different organic compounds
      presented apparently different seasonal characteristics, reflecting their
      different dominant emission sources, such as coal combustion, biomass burning and
      cooking emission. The abundance and origin of these organic compounds are
      discussed to reveal seasonal air pollution characteristics of Beijing.

PMID- 16083947
TI  - Ras initiates phosphatidyl-inositol-3-kinase (PI3K)/PKB mediated signalling
      pathways in untransformed human peripheral blood T lymphocytes.
AB  - Activation of T lymphocytes through costimulation of the T cell receptor/CD3
      complex (TCR/CD3) and coreceptors (e.g. CD2 or CD28) leads to production of the
      growth factor interleukin-2 (IL-2) and subsequent proliferation. For these
      activation processes, remodelling of the actin cytoskeleton plays an important
      functional role. We have shown that the activity of the actin-remodelling protein
      cofilin is crucially involved in T lymphocyte activation processes. In
      unstimulated human peripheral blood T lymphocytes (PB-T) cofilin exists in its
      inactive ser-3-phosphorylated form. T lymphocyte activation through costimulation
      of TCR plus the coreceptors CD28 or CD2, respectively, induces the
      dephosphorylation of cofilin. Concomitantly, cofilin associates with the actin
      cytoskeleton. The functional importance of cofilin for T lymphocyte activation
      was shown employing cell permeable peptides which block binding of cofilin to
      actin. In human PB-T these peptides impair the formation of the immunological
      synapse and inhibit the induction of T lymphocyte proliferation and cytokine
      production. The serine phosphatases PP1 and PP2A dephosphorylate cofilin in T
      lymphocytes. Importantly, a PKC-Ras-MEK/PI3K-cascade links costimulation of PB-T
      through TCR/CD3 and CD28 to activation of cofilin through dephosphorylation.
      Notably, the induction of cofilin dephosphorylation requires the combined
      activities of two Ras-effectors, namely MEK and PI3K. With respect to PI3K, this
      result was unexpected since so far it was generally assumed that-unlike in other
      cell types-Ras is not able to activate PI3K in T lymphocytes, as concluded from
      experiments performed with the human T-lymphoma line Jurkat. This discrepancy
      implied that the signalling events upstream of PI3K differ between PB-T and
      Jurkat cells. In line with this, we found that in PB-T the PI3K-inhibitors
      wortmannin and LY294002 block activation induced cofilin dephosphorylation and
      its association with the actin cytoskeleton. In Jurkat cells, however, where
      cofilin is present mainly in its non-phosphorylated form and permanently
      associated with the actin cytoskeleton, wortmannin and LY294002 do not block
      these events. Studies by others employing these PI3K-inhibitors have also led to
      such contradictory results: While in stimulated PB-T these inhibitors repress
      expression of IL-2, they even enhance IL-2 expression in Jurkat cells. These
      findings show that signalling events in Jurkat cells are not representative for
      signalling processes in untransformed human T lymphocytes. Importantly, our data
      demonstrate that-rebutting a persistent dogma-a T-cell specific uncoupling of
      PI3K from Ras does not exist.

PMID- 16083948
TI  - A prospective randomised controlled trial of intermittent self-catheterisation
      vs. supra-pubic catheterisation for post-operative bladder care following radical
      hysterectomy.
AB  - OBJECTIVE: To determine the potential benefits of ISC (intermittent self
      catheterisation) over SPC (supra-pubic catheterisation) in the post-operative
      bladder care of women following radical hysterectomy. METHODS: A prospective
      randomised controlled trial of women treated by radical hysterectomy for early
      stage cervical cancer. RESULTS.: 40 women were recruited to the study, 21 to ISC
      and 19 to SPC. All patients randomised to ISC were able to learn the technique of
      ISC satisfactorily following a period of pre-operative training. The day 3 and
      day 5 positive CSU (catheter specimen of urine) rate was significantly higher in
      the ISC group (42% and 63%) compared to the SPC group (6% and 18%), P = 0.05 and
      P = 0.004, respectively). Eight of 17 patients randomised to SPC (47%) documented
      having symptoms/problems arising from the SPC site of which 4 (23%) were shown to
      have a positive wound swab. There was no significant difference in length of
      period for bladder care between the two groups, P = 0.83. However, there were
      significant differences in patient acceptability (P = 0.009), freedom to lead a
      normal life (P = 0.000), disturbance at night (P = 0.006) and patient
      anxiety/embarrassment (P = 0.005) between the two groups. CONCLUSIONS: Patients
      are able to learn the technique of ISC without difficulty. Despite a greater
      urinary tract infection rate, the high incidence of SPC site problems can be
      avoided by use of ISC. The technique of ISC was seen to be more acceptable to
      patients allowing fewer disturbances at night, greater freedom to lead a normal
      life during the day and less anxiety/embarrassment compared to SPC.

PMID- 16083949
TI  - Potentiation of the radiation effect with genistein in cervical cancer cells.
AB  - OBJECTIVE: Early stage cervical cancer is treated with surgery or radiation with
      equivalent results. Radiation is used for curative therapy of locally advanced
      disease and is combined with additional anti-tumor agents to improve control. We
      determined the potential role of genistein as a radiosensitizer for cervical
      cancer cells. METHODS: Human cervical cell lines (CaSki and ME180) were used.
      Sensitivity of cells to genistein, radiation and the combination was determined
      by colony assays. Western blotting was used to study the expression of cell
      response-related gene products. RESULTS: Genistein results in the dose-dependent
      inhibition of all cell lines (2.5-40.0 microM). Effect of genistein on the
      radiosensitivity of the two cervical tumor cells was variable. Me180 cells were
      more sensitive at 20 and 40 microM of genistein. At 40 microM, less than 5% of
      Me180 cells survived the radiation (200-800 cGy). Potentiation of the radiation
      effect in CaSki cells was seen (500-800 cGy). The most significant enhancement of
      radiosensitivity was seen at 20 and 40 microM genistein at 500 and 800 cGy. G(2)M
      arrest was demonstrated only in ME180 cells with genistein. There was significant
      inhibition of Mcl-1 by genistein that correlated with increase in
      radiosensitivity in Me180 cells. Activated pAKT (Thr 308) was inhibited with
      genistein and radiation in CaSki cells. CONCLUSIONS.: Genistein inhibits growth
      of cervical cancer cells. Genistein results in variable and significant
      enhancement of the radiation effect that may be partially mediated by G(2)M
      arrest, Mcl-1 and activation of the AKT gene.

PMID- 16083950
TI  - Metachronous metastases from renal cell carcinoma to uterine cervix and vagina:
      case report and review of literature.
AB  - BACKGROUND: Although renal cell carcinoma (RCC) is characterized with
      unpredictable clinical presentation, multiple genital tract metastases are still
      surprising and mode of spread is obscure. CASE: We report a case of RCC
      metastases to uterine cervix and vagina 1 year after radical nephrectomy in a 19
      year-old virgin. To our knowledge, this case is the second youngest patient with
      RCC metastasis to vagina, and also third patient with RCC metastasis to uterine
      cervix. CONCLUSION: Detection of genital lesion may precede diagnosis of RCC. The
      primary renal tumor was mostly left sided. Retrograde venous extension seems to
      be the most plausible mode of spread. Limited total experience and variability in
      therapeutic approach prevent generalizations regarding prognosis, optimal
      treatment and survival.

PMID- 16083951
TI  - When is a sex difference not a sex difference?
AB  - Brain sexual differentiation in mammals requires activity of gonadal hormones;
      organizational effects of these steroids on brain development occur early in life
      while activational ones in adulthood ensure appropriate and timely sex-specific
      behaviors. This traditional view has long served as a reliable model for sexual
      differentiation of reproductively relevant brain structures. Here, we take a
      fresh look at this model but refocused in the context of sexual differentiation
      of non-reproductive parameters and with an emphasis on the hippocampus, a
      telencephalic brain structure predominantly involved in cognition and stress
      regulation. We explore sex differences in morphology, neurochemistry, and
      hippocampal-dependent behaviors to propose a new prototype that can be used to
      explain and further investigate the effects of steroid hormones, those
      synthesized gonadally or intracerebrally, on hippocampal development and
      function. We also propose that a new vernacular be employed, one that
      distinguishes hormonally modulated responses from sex differences, and argue
      these are mechanistically and functionally distinct. Understanding when and how
      the sexes are different is as important as understanding when and how they are
      the same, at the biological, social, and cultural level.

PMID- 16083952
TI  - Behavioral characterization of morphine effects on motor activity in mice.
AB  - A biphasic effect of morphine on locomotion has been extensively described.
      Nevertheless, the effects of this opioid on other behavioral parameters have been
      overlooked. The aim of the present study was to verify the effects of different
      doses of morphine on motor behaviors observed in an open-field. Adult female mice
      were injected with saline or morphine (10, 15 and 20 mg/kg, i.p.) and observed in
      an open-field for quantification of locomotor and rearing frequencies as well as
      duration of immobility and grooming. The lowest dose of morphine decreased
      locomotion (and increased immobility duration) while the highest dose increased
      it. All doses tested decreased rearing and grooming. Thus, the effects of
      morphine on locomotion do not parallel to its effects on rearing and grooming.
      Our results indicate that locomotion not always reflects the effect of drugs on
      motor activity, which can be better investigated when other behavioral parameters
      are concomitantly taken into account.

PMID- 16083953
TI  - EEG theta and gamma responses to semantic violations in online sentence
      processing.
AB  - We explore the nature of the oscillatory dynamics in the EEG of subjects reading
      sentences that contain a semantic violation. More specifically, we examine
      whether increases in theta ( approximately 3-7 Hz) and gamma (around 40 Hz) band
      power occur in response to sentences that were either semantically correct or
      contained a semantically incongruent word (semantic violation). ERP results
      indicated a classical N400 effect. A wavelet-based time-frequency analysis
      revealed a theta band power increase during an interval of 300-800 ms after
      critical word onset, at temporal electrodes bilaterally for both sentence
      conditions, and over midfrontal areas for the semantic violations only. In the
      gamma frequency band, a predominantly frontal power increase was observed during
      the processing of correct sentences. This effect was absent following semantic
      violations. These results provide a characterization of the oscillatory brain
      dynamics, and notably of both theta and gamma oscillations, that occur during
      language comprehension.

PMID- 16083954
TI  - Comparing language lateralization determined by dichotic listening and fMRI
      activation in frontal and temporal lobes in children with epilepsy.
AB  - We investigated the relationship between ear advantage scores on the Fused
      Dichotic Words Test (FDWT), and laterality of activation in fMRI using a verb
      generation paradigm in fourteen children with epilepsy. The magnitude of the
      laterality index (LI), based on spatial extent and magnitude of activation in
      classical language areas (BA 44/45, 21/22, 39) differed significantly for
      patients classified with unilateral left, compared to bilateral, language
      representation based on FDWT scores. Concordance with fMRI was higher for those
      classified with unilateral left, than bilateral language representation on the
      FDWT. Of note, asymmetry in temporal lobe, rather than frontal lobe, activation
      was more strongly related to the LI from the dichotic listening test. This study
      shows that the FDWT can provide a quick and valid estimate of lateralization in
      pre-surgical candidates, which can be readily adopted for other clinical or
      research purposes when an estimate of language dominance is desired.

PMID- 16083955
TI  - Effect of surface reaction layer on grindability of cast titanium alloys.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of the cast
      surface reaction layer on the grindability of titanium alloys, including free
      machining titanium alloy (DT2F), and to compare the results with the grindability
      of two dental casting alloys (gold and Co-Cr). METHODS: All titanium specimens
      (pure Ti, Ti-6Al-4V and DT2F) were cast using a centrifugal casting machine in
      magnesia-based investment molds. Two specimen sizes were used to cast the
      titanium metals so that the larger castings would be the same size as the smaller
      gold and Co-Cr alloy specimens after removal of the surface reaction layer (alpha
      case). Grindability was measured as volume loss ground from a specimen for 1 min
      using a handpiece engine with a SiC abrasive wheel at 0.1 kgf and four
      circumferential wheel speeds. RESULTS: For the titanium and gold alloys,
      grindability increased as the rotational speed increased. There was no
      statistical difference (p>0.05) in grindability for all titanium specimens either
      with or without the alpha-case. Of the titanium metals tested, Ti-6 Al-4V had the
      greatest grindability at higher speeds, followed by DT2F and CP Ti. The
      grindability of the gold alloy was similar to that of Ti-6 Al-4V, whereas the Co
      Cr alloy had the lowest grindability. SIGNIFICANCE: The results of this study
      indicated that the alpha-case did not significantly affect the grindability of
      the titanium alloys. The free-machining titanium alloy had improved grindability
      compared to CP Ti.

PMID- 16083956
TI  - Allelic expression and quantitative RT-PCR study of TAp73 and DeltaNp73 in non
      Hodgkin's lymphomas.
AB  - p73 shares structural and functional homology to p53. p73 generates different
      proteins using alternative promoters and splicing which have different biological
      characteristics. We investigated the pattern (monoallelic or biallelic) of
      expression of TAp73 and DeltaNp73 in normal lymphocytes and lymphomas using two
      p73 polymorphisms. We found monoallelic expression of TAp73 in normal lymphocytes
      and tumors, and a selective expression of AT allele in all cases. Moreover, the
      quantitative expression analysis revealed DeltaNp73 over-expression in both B-
      and T-cell lymphomas comparing with normal lymphoid cells, suggesting a role in
      tumorigenesis. Finally, we have confirmed that although DeltaNp73 over-expression
      could be an alternative mechanism of p53 inactivation, both alterations may
      appear together.

PMID- 16083957
TI  - Similarity and divergence in the development and expression of the mouse and
      human antibody repertoires.
AB  - Over the past twenty years diverse groups in Northeast Asia, Western Europe, and
      North America have competed to map, sequence, and characterize the immunoglobulin
      loci of mouse and man. Now that this work is near completion, it has become
      evident that the human and mouse germline repertoires share broad similarities in
      gene composition, organization, and other general principles. In spite of these
      similarities, the repertoires expressed by adult mice and humans are distinct and
      differ from each other in detail. In both species the mechanisms used to create
      repertoire diversity appear designed to generate a random range of antigen
      binding sites. However, a detailed analysis reveals significant constraints in
      the sequence and amino acid composition of the third complementarity region of
      the H chain (CDR-H3), which lies at the center of the antigen binding site. The
      mechanisms used to regulate the composition of the repertoire, their significance
      to the development and maintenance of immune competence, and the contribution of
      violation of normal repertoire boundaries to the development of diseases of
      immune function remain foci of ongoing investigation.

PMID- 16083958
TI  - Antibody repertoire development in the sheep.
AB  - The model of immunoglobulin (Ig) repertoire diversification in sheep has evolved
      dramatically in recent years. A process thought to involve the rearrangement of a
      very limited number of variable (V), diversity (D) and joining (J) segments
      followed by intense, antigen (Ag)-independent, somatic hypermutation is now known
      to be less recombinatorially restrictive and to involve fewer mutational events.
      Although mutation rates are now lower than previously thought, the somatic
      hypermutation process itself is no less critical to the development of the
      primary Ig repertoire in sheep. Recent studies have shown that those B cells that
      fail to mutate will die via apoptosis. Much of the V(D)J rearrangement is thought
      to occur in the fetal liver and spleen prior to development of the ileal Peyer's
      patch (PP) at approximately day 100 of gestation. Although de novo Ig
      rearrangement likely does not occur in the ileal PP, this tissue is a site of
      massive B-cell proliferation, selection and Ig diversification through somatic
      hypermutation.

PMID- 16083959
TI  - The antibody repertoire in evolution: chance, selection, and continuity.
AB  - All jawed vertebrates contain the genetic elements essential for the function of
      the adaptive/combinatorial immune response, have diverse sets of natural
      antibodies resulting from segmental gene recombination, express comparable
      functional repertoires and can produce specific antibodies following appropriate
      immunization. Profound variability occurs in the third hypervariable (CDR3)
      segments of light and heavy chains even within antibodies of the same ostensible
      specificity. Germline VH and VL elements, as well as the joining (J) segments are
      highly conserved among the distinct vertebrate species. Conservation is
      particularly noted among the VH3-like sequences of all jawed vertebrates in the
      FR2 and FR3 segments, as well as in the FGXGT(R or K)L J-segment characteristic
      of light chains and TCRs and the WGXGT(uncharged)VT JH segments. Human VH3-53 and
      Vlambda6 family orthologs may be present over the entire range of vertebrates.
      Models of the three-dimensional structures of shark VH/VL combining sites
      indicate similarity in framework structure and comparable CDR usage to those of
      man. Although carcharhine shark VH regions show greater than 50% identity to the
      human VH germline prototype, searches of lower deuterostome and invertebrate
      databases fail to detect molecules with significant relatedness. Overall,
      antibodies of jawed vertebrates show tremendous individual diversity, but are
      constructed incorporating design features that arose with the evolutionary
      emergence of the jawed vertebrates and have been conserved through at least 450
      million years of evolutionary time.

PMID- 16083960
TI  - Sedimentation rates and erosion processes in the lagoon of Venice.
AB  - Since the early 1990s in the lagoon of Venice, especially in the central basin,
      the surface sediment underwent high re-suspension and sedimentation changes and
      water turbidity increased both because of the disappearance of the macroalgal
      coverage and the harvesting of the Manila clam Tapes philippinarum Adams and
      Reeve, which had rapidly colonised the bottom free of macrophytes. Clams are
      harvested with hydraulic and mechanical dredges which remove and re-suspend
      surface sediments causing the transport and loss of the finest materials.
      Sediment transport and re-deposition in the lagoon have been monitored with
      sediment traps placed onto the bottoms near the Malamocco mouth (st. A), the Lido
      watershed (st. B) and the mainland (sts. C and D). From 1989-1993 to 1998-1999
      sedimentation rates increased significantly at st. A (from 41 to 228 kg DW m(-2)
      year(-1)), st. B (from 65 to 760 kg DW m(-2) year(-1)) and st. C (from 140 to 721
      kg DW m(-2) year(-1)), while at st. D sedimentation rates increased only by ca.
      20%. In parallel sediment grain-size changed with a loss of the finest fraction
      especially near the mainland. The erosion or sedimentation status, acquired by
      utilizing sedimentation devices placed onto the bottoms, showed that sts. B, C, D
      were affected by sediment losses, while st. A, populated by seagrasses and
      characterised by seasonal variations which depend on the shoot development, did
      not show any significant bathymetric change on an annual basis. The highest
      sediment erosion was recorded at st. D (ca. 3.6 cm year(-1)) whereas a loss of
      ca. 1.5 and 0.5 cm year(-1) was found at sts. C and B, respectively, which
      accounted for a mean loss in the central lagoon of ca. 1.2 million tonnes year(
      1). Those data agree with the previous indirect estimation of sediment loss which
      was based on the number of fishing boats operating in the lagoon on an annual
      basis.

PMID- 16083961
TI  - Cellular alterations in Mytilus galloprovincialis (LMK) and Tapes philippinarum
      (Adams and Reeve, 1850) as biomarkers of environmental stress: field studies in
      the Lagoon of Venice (Italy).
AB  - A long-term biomonitoring study was carried out in the Lagoon of Venice (North
      East Italy) with the aim of evaluating variations in biological responses to
      environmental stress in estuarine bivalves. Two different species, the mussel
      Mytilus galloprovincialis and the clam Tapes philippinarum, both widespread in
      the Lagoon, were studied in several sites. Two cellular biomarkers: lysosomal
      membrane stability in digestive cells and thickness of digestive epithelia, were
      evaluated in native organisms (on a seasonal basis), and in organisms which have
      been transferred from a reference site to several differently influenced ones.
      Results indicate that, to some extent, both test and organisms were able to
      highlight site-specific differences, but the effects of pollution were generally
      more easily detected by reduction in lysosomal stability than by reduction in
      digestive tubule epithelium. Further findings show that the inherent variability
      of a number of natural parameters, particularly in the reference sites, produced
      less effective results when biological responses in the reference organisms were
      compared with the polluted ones. The assessment of the two conditions was most
      valuable when they referred to the 25-75% range of values comprised within the
      seasonal medians, recorded respectively in control and polluted sites. Impaired
      from steady states were most effectively distinguished when the control values
      were medians from two reference locations. Lately, the overall results indicate
      that both biomarkers are more suitably deployed through the translocation
      approach, revealing it to be more sensitive than traditional biomonitoring, at
      least in the sense that it may overcome problems related to the adaptation of
      native organisms to sub lethal chronic pollution levels.

PMID- 16083962
TI  - Reconstruction of historical trends of PCDD/Fs and PCBs in the Venice Lagoon,
      Italy.
AB  - Historical trends of PCDD/Fs and PCBs from the year 1900 have been reconstructed
      for the Venice Lagoon area by using a fugacity-based dynamic multimedia model. A
      novel approach to estimate the inputs to the system was applied. Emissions to the
      lagoon were estimated by studying dated sediment cores taken from salt marshes
      located in the lagoon area. These cores have recently proven to be a suitable
      tool to reconstruct the temporal trends of atmospheric deposition of POPs.
      According to the model, concentrations of PCBs and PCDD/Fs in air and water
      reflect the trends of their production and usage, peaking during the 1960s. The
      peaks in the sediment were delayed by 5-40 years depending on the congener.
      Predicted concentrations are in good agreement with experimental results. The
      most important input parameters, identified by a sensitivity analysis, are the
      degradation constants, K(ow), the Henry's law constant, vapour pressure, active
      sediment depth, sediment resuspension, and deposition rates, and water residence
      time in the lagoon.

PMID- 16083963
TI  - Temporal trends in the sources of PCDD/Fs to and around the Venice Lagoon.
AB  - Two salt marsh cores were collected from the Venice Lagoon, Italy, and analysed
      for PCDD/Fs. The samples were undisturbed and had an approximately constant
      accumulation rate. Radiochemical chronologies were established for the different
      core sections. The PCDD/F pattern in the surficial layers was very similar to
      that of atmospheric deposition measured in the same area. However, the pattern
      changed with increasing depth and was very different in the deeper sections,
      where the highest PCDD/F concentrations were measured. This layer was dated
      around the 1950s. Deeper layers have a profile similar to the surficial one.
      Undisturbed salt marsh cores appear to be a reliable tool for the reconstruction
      of temporal trends in the atmospheric deposition of persistent organic
      pollutants. It is proposed that the trends in the core reflect atmospheric
      deposition that probably results from the sum of two different contributions:
      emissions of the industrial district of Porto Marghera on the edge of the lagoon
      and the regional background.

PMID- 16083964
TI  - Coexistent sarcoidosis and HIV infection: an immunological paradox?
AB  - The CD4 lymphocyte plays a pivotal role in both sarcoidosis and HIV infection.
      Caring for a patient with both conditions represents a diagnostic and therapeutic
      challenge. We describe a patient, previously diagnosed with sarcoidosis, who
      subsequently contracted HIV infection. Manifestations of sarcoidosis were
      clinically silent until highly active anti-retroviral therapy was instituted. Her
      condition improved with the institution of corticosteroids. The diagnostic and
      therapeutic dilemmas encountered in patients with both conditions will be
      discussed including a complete review of the literature.

PMID- 16083965
TI  - Receptor systems: will mining the receptorome yield novel targets for
      pharmacotherapy?
AB  - We have recently defined the receptorome as 'that part of the proteome encoding
      receptors'. In this article, I provide a general overview of the members of the
      receptorome as well as methods used to screen the receptorome-both in silico and
      physically. Case histories of receptorome-based discovery efforts are then
      highlighted and the relevance of this approach to the discovery and validation of
      molecular targets for drug abuse treatment is emphasized.

PMID- 16083966
TI  - Medications development: successes and challenges.
AB  - The National Institute on Drug Abuse has funded a medications program that has
      concentrated on the development of medications for opiate and cocaine dependence.
      Levomethadyl acetate (LAAM) and buprenorphine and buprenorphine/naloxone
      sublingual tablets were developed in conjunction with pharmaceutical partners and
      approved by the Food and Drug Administration. The remaining challenges for
      medications development for opiate dependence involves Phase IV studies in
      special populations, for example, pregnant opiate-dependent patients, and to
      translate neuroscience-based findings into treatments. Several marketed
      medications have shown initial efficacy to reduce cocaine use in well-controlled
      clinical trials. Disulfiram has been shown to reduce cocaine use in several
      clinical trials, while baclofen, modafinil, naltrexone, ondansetron, tiagabine,
      and topiramate have shown preliminary efficacy in initial clinical studies.
      Confirmatory studies of many of these medications is underway. More recently, the
      NIDA medications program has evaluated medications for their ability to reduce
      methamphetamine use. To date, no medications tested have shown efficacy to reduce
      methamphetamine use. Both marketed medications and investigational agents will be
      tested. Finally, NIDA has begun to test medications for efficacy to reduce
      cannabis use. Initial studies are underway. Both agonist and antagonist
      approaches will be evaluated. Additionally, medications will be tested in
      cannabis-dependent patients for the management of insomnia, withdrawal, and
      concurrent depression.

PMID- 16083967
TI  - Method of construction of a MRI-based tabular database of 3D stereotaxic co
      ordinates for individual structures in the basal ganglia of Macaca mulatta.
AB  - Primate models are commonly used in Parkinson's disease research to study
      stereotaxic strategies that demand accurate localization of the structures in
      basal ganglia. We demonstrate a method to construct an extensive tabular database
      of 3D stereotaxic co-ordinates of various basal ganglia structures from high
      quality magnetic resonance (MR) images of 47 adult female 3-5 kg rhesus monkeys.
      For each animal, the structures in the basal ganglia were traced as they appeared
      on the axial MR images. Their maximal outlines were projected in the axial plane
      to create a stack of images and X, Y, Z co-ordinates were calculated for margins
      of each structure. These co-ordinates and the outlines of the individual nuclei
      help delineate a "common area," which was further narrowed down to a point that
      represents the 'most reliable target point' (MRTP) in subthalamic nucleus, globus
      pallidum, caudate and putamen on both sides. Common area and MRTP represent the
      region that can most definitely be associated with a structure and hence the most
      definite target for a given structure. The goal of this study is to demonstrate
      the method of construction, discuss the feasibility and usefulness of such a
      tabular database that could potentially add to accuracy of localization while
      using atlas-based stereotaxy. Though use of MRI remains a standard practice and
      advances in imaging have made targeting for functional surgery more accurate, in
      developing countries that implies prohibitive costs per procedure. Population
      based human databases similar to the monkey database described here, when used
      along with less expensive imaging modalities can reduce the costs considerably as
      well as add to the accuracy of targeting.

PMID- 16083968
TI  - The diverse functions of CD1d-restricted NKT cells and their potential for
      immunotherapy.
AB  - CD1d-restricted NKT cells have been identified as an important component of the
      immune system that have the capacity both to augment beneficial host immunity and
      to prevent harmful autoimmunity. These cells have the ability to produce a wide
      variety of cytokines, including both proinflammatory and antiinflammatory
      cytokines that can have multiple different effects on the outcome of immune
      reactions. The discovery that these T cells are activated by specific recognition
      of glycolipids in the glycosylceramide family has led to new approaches to
      manipulate the pleiotropic functions of these cells. Here, we review the multiple
      activities that have been attributed to NKT cells in a variety of different
      disease models, and the current state of our understanding of the mechanisms that
      control the functional outcome of NKT cell activation.

PMID- 16083969
TI  - Activated inflammatory T cells correlate with lesion size in human cutaneous
      leishmaniasis.
AB  - Leishmaniasis is an important parasitic disease affecting millions worldwide. In
      attempts to understand the clinical relevance of immunological measurements as
      determined using flow cytometry, several immunological phenotypes were determined
      for a group of well defined human leishmaniasis patients and correlated with
      clinical measurements of the disease (Montenegro skin test (MST) and lesion
      area). The analysis demonstrated a positive correlation between the MST size and
      the frequency of ex vivo recent activated CD4(+) T cells. In contrast, higher
      frequencies of recent activated CD8(+) T cells were correlated with a smaller MST
      size. Moreover, a positive correlation was observed between the lesion total area
      and the frequency of activated CD69(+) (ex vivo) and CD40L(+) (cultured with
      Leishmania soluble antigen (SLA)) T lymphocytes. Finally, larger lesions were
      also correlated with a higher frequency of SLA specific inflammatory cytokine
      (IFN-gamma or TNF-alpha) producing lymphocytes. These studies demonstrate that
      immunological markers are correlated with clinical indicators of human
      leishmaniasis and serve to better understand the evolution of this important
      parasitic disease.

PMID- 16083970
TI  - Partial nucleotide sequences and expression patterns of frog (Rana pipiens)
      ephrin-A2 and ephrin-A5 mRNA.
AB  - We have generated 362 bp and 547 bp partial sequences for Rana pipiens ephrin-A2
      and ephrin-A5 mRNA, respectively. Translation homologies for the comparable
      segments of cDNA of chicken, mouse and human are 90.8, 86.9 and 84.4% for the
      ephrin-A2 sequence and 85.7, 85.0 and 85.0% for the ephrin-A5 sequence.
      Digoxigenin-labeled riboprobes were prepared and applied by means of in situ
      hybridization to whole-mounts of the brains of mature adults and expression
      patterns in tadpoles were also explored. The RNA probes revealed similar
      posterior (high) to anterior (low) expression gradients in the adult tectum,
      demonstrating that both ephrin-As are expressed in the adult Ranid frog tectum.
      Only the ephrin-A2 probe was tested on tadpole brain, yielding an appropriately
      graded expression pattern similar to the adult.

PMID- 16083971
TI  - Lower brain-derived neurotrophic factor in serum of relapsing remitting MS:
      reversal by glatiramer acetate.
AB  - Neuronal growth factors may exert a neuroprotective effect in multiple sclerosis
      (MS). We found reduced levels of brain-derived neurotrophic factors (BDNF) in the
      serum and CSF of relapsing-remitting MS patients, which was reversed by therapy
      with glatiramer acetate. BDNF may play a protective role in MS, and
      immunomodulation therapy, such as with glatiramer acetate, may enhance the action
      this mechanism.

PMID- 16083972
TI  - The impact of glucocorticoid receptor gene polymorphisms on glucocorticoid
      sensitivity is outweighted in patients with multiple sclerosis.
AB  - Glucocorticoid (GC) sensitivity varies considerably in healthy controls as well
      as in patients with chronic inflammatory diseases like multiple sclerosis (MS).
      We investigated whether polymorphisms in the glucocorticoid receptor (N363S,
      ER22/23EK, and the BclI) were responsible for altered GC sensitivity. In healthy
      controls we found an association between the N363S allele of the GR and a reduced
      peripheral GC sensitivity. In MS patients neither the variant N363S, the BclI
      RFLP nor the ER22/23EK allele were found to be associated with GC sensitivity. GC
      sensitivity is probably in part genetically influenced in healthy controls, but
      in MS patients other factors seem to have more impact on GC sensitivity.

PMID- 16083973
TI  - Holoprosencephaly--report of two cases.
AB  - Holoprosencephaly (HPE) is a developmental defect resulting from incomplete
      cleavage of the embryonic forebrain structures during early embryogenesis. It
      includes a series of rare complex disorders. Chromosomal abnormalities, single
      gene disorders and teratogenic agents are responsible for holoprosencephaly. We
      report two rare cases of alobar HPE with a rudimental nasal structure (proboscis)
      located under the eyes. One of the patients survived for 9 months and the other
      one survived 40 days.

PMID- 16083974
TI  - Reanimating limbs after injury or disease.
AB  - Many diseases and injuries lead to loss of motor function. Can we reanimate
      paralyzed limbs to produce effective, graceful movements? Recent insights into
      the function of the motor system and greatly improved computing capabilities have
      made this a realistic goal, even in the absence of regeneration of motor
      pathways. Some approaches involve stimulating muscles, nerves or the spinal cord
      below the level of a lesion. Others involve recording a subject's intention from
      the cortex, and using this intention to control computers, robots or systems for
      stimulating the limbs. Here, we critically analyze the possibilities and
      limitations of various approaches for restoring motor function based on recent
      human trials and underlying neuroscience research.

PMID- 16083975
TI  - Who's on first? What's on second? The time course of learning in corticostriatal
      systems.
AB  - The prefrontal cortex and basal ganglia are known to be crucial for learning
      arbitrary sensorimotor associations (e.g. knowing to stop at red traffic lights).
      However, little is known about the timing of learning-related activity in these
      brain systems. Conventional wisdom suggests that the prefrontal cortex should
      drive learning-related changes in the basal ganglia. However, it is possible that
      the basal ganglia are instead responsible for the development of learning-related
      activity in prefrontal cortex. Indeed, recent work using methods for recording in
      the prefrontal cortex and basal ganglia simultaneously suggests that learning
      related activity emerges first in the basal ganglia. Here, these studies are
      reviewed and integrated with the known anatomy of corticostriatal connections.
      Testable hypotheses regarding corticostriatal interactions during learning are
      proposed.

PMID- 16083976
TI  - Effects of 17beta-estradiol exposure in the mussel Mytilus galloprovincialis: a
      possible regulating role for steroid acyltransferases.
AB  - Mussels (Mytilus galloaprovincialis) were exposed to different concentrations of
      estradiol (20, 200, and 2000 ng/L) in a semi-static regime (1-day dosing
      intervals) for up to 7 days in an attempt to see how mussels deal with exogenous
      estrogenic compounds. Whole tissue free-estradiol levels were only significantly
      elevated at the high exposure dose, whereas total-estradiol (free+esterified)
      sharply increased in a dose-dependent manner, from 2 ng/g in controls to 258 ng/g
      at the high exposure group. Neither free nor esterified testosterone levels
      showed significant differences between control and exposed organisms. The results
      suggest the existence of mechanisms that allow mussels to maintain their hormonal
      levels stable, with the exception of the high exposure dose, and the important
      role that fatty acid esterification, e.g. palmitoyl-CoA:estradiol
      acyltransferases, may play within those mechanisms. Additionally, the activity of
      17beta-hydroxysteroid dehydrogenase (17beta-HSD), 5alpha-reductase, P450
      aromatase, and estradiol-sulfotransferases were investigated in digestive gland
      microsomal and cytosolic fractions. All these activities were differently
      affected by estradiol exposure. Overall, the study contributes to the better
      knowledge of molluscan endocrinology, and defines new mechanisms of regulation of
      free steroid-levels in mussels.

PMID- 16083977
TI  - The effect of lead on the metabolic and energetic status of the Yabby, Cherax
      destructor, during environmental hypoxia.
AB  - The concomitant effects of Pb and hypoxia on respiration and muscle energy status
      were examined in the freshwater crayfish Cherax destructor to determine if Pb
      intoxication exacerbated the effects of hypoxia. C. destructor, either
      intoxicated for 14 days with 0.5 mgL(-1)Pb, or from Pb-free control conditions,
      were subjected to progressive hypoxia at -2.7 kPah(-1) to a O2 partial pressure
      in the water (PwO2) of 1.33 kPa. This hypoxia was then sustained for 3 h. Pb
      exposure reduced O2-uptake (MO2) at all PwO2 above 1.33 kPa but without any
      saving in ventilation, implying that Pb either unlinked ventilation from actual
      O2 requirements or rendered O2 transfer across the gill less efficient. Hypoxia
      alone induced no change in the adenylate energy charge (AEC), total adenylate
      (TAN), ATP/ADP ratio or in the equilibrium constant for adenylate kinase
      K'(ADEN), apparently due to protection of ATP levels by arginine phosphate. Under
      maximal hypoxia (PwO2=1.33 kPa) the Pb-exposed crayfish increased muscle ADP by
      73% (tail) and 158% (chelae) but without any change in AMP, ATP or TAN. Thus, AEC
      declined (chelae AEC=0.71; tail AEC=0.85), as did the ATP/ADP ratio and K'(ADEN).
      L-Lactate increased in the muscle tissues of control but not Pb-exposed crayfish,
      consistent with a lowered O2 requirement in the Pb-exposed animals. The Pb
      intoxication slowed respiration and probably glycolysis, possibly altering the
      [ATP]:[ADP] equilibrium concentrations for adenylate kinase K'(AK). Lowered MO2
      during severe hypoxia slows oxidative phosphorylation and ADP accumulation could
      occur as non-utilised substrate and may reflect a transient disequilibrium.
      During this time ATP levels were protected by arginine phosphate. AEC is
      sensitive to Pb in hypoxic crayfish but the changes have low importance for the
      energetic competence of the crayfish. During sustained hypoxia the crayfish
      recovered their energy status regardless of the Pb-exposure and this was,
      therefore, not a feature of Pb intoxication. Consequently, the ADP was recovered
      into the ATP pool of the hypoxic crayfish, and demand on arginine phosphate
      relieved. The Pb exposure did not otherwise exacerbate the effect of sustained
      hypoxia and C. destructor appeared to cope well with Pb intoxication, apparently
      by a specific Pb-induced hypometabolism separate from hypoxic response. Lowered
      metabolism as a survival response has limitations in the longer term and the
      implications for crustaceans generally warrant further study.

PMID- 16083978
TI  - Firsts in cardiology: milestones and vital discoveries.
AB  - The modern day cardiology practice thrives on the extraordinary discoveries made
      in the understanding of the cardiovascular science and in the development of
      diagnostic and therapeutic methods. In this paper, the milestones and vital
      discoveries in the field of cardiology are described in chronologic order.

PMID- 16083979
TI  - Exercise-induced second-degree atrioventricular block.
AB  - In this report we describe the case of a 56-year-old woman with normal 1:1 AV
      conduction at rest who developed 2:1 AV block during treadmill exercise testing.
      Electrophysiological study documented 2:1 AV block proximal to the His bundle
      with reappearance of 1:1 AV conduction at a higher pacing atrial rate. A gap
      phenomenon involving a proximal and distal part of the AV node may be a likely
      explanation of paradoxical AV conduction in our case.

PMID- 16083980
TI  - Effects of synthetic progestagens on autonomic tone, neurohormones and C-reactive
      protein levels in young healthy females in reproductive age.
AB  - BACKGROUND: Heart rate variability and baroreceptor sensitivity are measures of
      autonomic control. While progestagen-containing replacement therapy in
      postmenopausal women adversely affects autonomic balance, the impact of hormonal
      contraceptives with synthetic progestagens on autonomic activity, neurohormones
      and C-reactive protein levels is not well characterized. METHODS AND RESULTS: We
      analyzed parameters of heart rate variability and baroreceptor sensitivity in
      young healthy females without (n = 27) or on oral contraceptives with synthetic
      progestagens (n = 31). Demographic characteristics were not different among the
      examined groups. Total power (controls: 5682+/-3618 vs. hormones: 4800+/-2957
      ms2; NS), standard deviation of beat-to-beat intervals (SDNN; 66+/-24 vs. 63+/-20
      ms; p = 0.74), other time- and frequency-dependent parameters of heart rate
      variability and baroreceptor sensitivity (6.0+/-3.2 vs. 6.5+/-2.7 ms/mm Hg; NS)
      were not significantly different among the groups. Total cholesterol and
      triglyceride as well as C-reactive protein (CRP) levels were significantly higher
      in users of hormonal contraceptives than in non-users (cholesterol: 187+/-37 vs.
      166+/-28 mg/dL; p = 0.05; triglycerides: 110+/-35 vs. 68+/-30 mg/dL; p = 0.01;
      CRP: 2.7+/-2.1 vs. 1.0+/-1.4 mg/L; p < 0.001). Heart rate variability,
      baroreceptor sensitivity, lipid parameters and CRP levels were not affected
      during the ovarian cycle in non-users of hormonal contraception. CONCLUSIONS: The
      use of oral contraceptives containing synthetic progestagens was not associated
      with a modulation of autonomic tone, while lipid parameters and CRP levels were
      adversely affected. These data suggest that synthetic progestagens in modern oral
      contraceptives do not modulate the autonomic balance, but probably affect the
      atherogenic risk profile of young females in reproductive age.

PMID- 16083981
TI  - A method for the construction of in frame substitutions in operons: deletion of
      the essential Escherichia coli holB gene coding for a subunit of the DNA
      polymerase III holoenzyme.
AB  - To investigate the putative five-gene operon at 24.9 min on the Escherichia coli
      genome, which comprises the genes pabC, yceG, tmk, holB and ycfH, a method for
      the construction of an in frame deletion strain of the essential E. coli holB
      gene was developed. HolB, also referred to as delta prime or delta', is a subunit
      of the DNA polymerase III (Pol III) holoenzyme. The holB gene was replaced by the
      kanamycin resistance gene kka1, coding for amino glycoside 3'-phosphotransferase
      kanamycin kinase. The kanamycin resistance gene was expressed under the control
      of the promoter(s) of the putative five-gene operon. The holB gene is essential
      for bacterial growth and the deletion of holB exhibits no polar effects on the
      adjacent genes tmk or ycfH in terms of cell viability. The method of the holB
      null construction presented in this work allows for a simplified studying of
      interactions between the different subunits of DNA polymerase III.

PMID- 16083982
TI  - Confidence intervals of similarity values determined for cloned SSU rRNA genes
      from environmental samples.
AB  - The goal of this research was to investigate the influence of the error rate of
      sequence determination on the differentiation of cloned SSU rRNA gene sequences
      for assessment of community structure. SSU rRNA cloned sequences from groundwater
      samples that represent different bacterial divisions were sequenced multiple
      times with the same sequencing primer. From comparison of sequence alignments
      with unedited data, confidence intervals were obtained from both a 'double
      binomial' model of sequence comparison and by non-parametric methods. The results
      indicated that similarity values below 0.9946 are likely derived from dissimilar
      sequences at a confidence level of 0.95, and not sequencing errors. The results
      confirmed that screening by direct sequence determination could be reliably used
      to differentiate at the species level. However, given sequencing errors
      comparable to those seen in this study, sequences with similarities above 0.9946
      should be treated as the same sequence if a 95% confidence is desired.

PMID- 16083983
TI  - The inhibitory effect of Penicillium camemberti and Geotruchum candidum on the
      associated funga of white mould cheese.
AB  - The diameter of pinpoint inoculated cheese contaminates (Cladosporium herbarum,
      Penicillium roqueforti, Penicillium caseifulvum and Penicillium commune),
      isolated from either the dairy environment or directly from cheese, were
      inoculated 24 h after inoculation of the secondary starters to simulate
      contamination at the critical point of the salt brine. Pure P. camemberti had the
      largest inhibitory effect on the C. herbarum contaminant. Adding G. candidum in
      mixed cultures weakened the inhibitory effect of P. camemberti on C. herbarum.
      Low levels of G. candidum (10(3) spore/ml) promoted visible growth effects of C.
      herbarum, and this was most pronounced in the early stages of growth. The
      interaction mechanism of C. herbarum was not affected by the choice of the strain
      of P. camemberti whereas the Penicillium contaminants were very sensitive to the
      choice of the P. camemberti strain. The presence of G. candidum in the mixed
      cultures seems to decrease the suppressing effect of pour-plated P. camemberti.
      No correlation of any kind was found in the pour-plated spore concentration
      totals by the inhibition of the C. herbarum and P. roqueforti contaminants
      whereas P. caseifulvum and P. commune were sensitive to this.

PMID- 16083984
TI  - Proteolysis in miniature cheddar-type cheeses manufactured using extracts from
      the crustacean Munida as coagulant.
AB  - Miniature (20 g) Cheddar-type cheeses were manufactured using enzymes extracted
      from the crustacean Munida or chymosin as coagulant. Cheeses were ripened at 8
      degrees C and samples were collected for analysis after 2, 6 and 12 weeks.
      Proteolysis was assessed by urea-polyacrylamide gel electrophoresis, which showed
      that cheeses manufactured with the Munida extracts had a higher extent of
      degradation of beta-casein than cheeses made using chymosin as coagulant.
      Patterns of proteolysis were also obtained by reverse-phase high-performance
      liquid chromatography (RP-HPLC) and matrix assisted laser desorption ionisation
      time of flight (MALDI-ToF) mass spectrometry. In general, the products of
      proteolysis were more complex in cheese made using the Munida extracts than in
      cheese made by chymosin as coagulant. Statistical analysis of results clearly
      discriminated the cheeses on the basis of coagulant used. Molecular mass of
      peptides found in cheese made using Munida extracts were similar to those of
      peptides commonly detected in cheeses made using chymosin as coagulant.

PMID- 16083985
TI  - Compensatory recovery of liver mass by Akt-mediated hepatocellular hypertrophy in
      liver-specific STAT3-deficient mice.
AB  - BACKGROUND/AIMS: Liver regeneration following hepatectomy is complicated and
      involves a variety of interacting factors. The present study was designed to
      study the roles of proliferation and hypertrophy of hepatocytes in liver
      regeneration following hepatectomy in liver-specific STAT3-knockout (LS3-KO) mice
      lacking mitogenic activity. METHODS: Partial hepatectomy was performed in LS3-KO
      and control mice. Liver regeneration was estimated by the liver weight, cell
      proliferation and cell size, and the related cellular signals were analyzed.
      RESULTS: Proliferation of hepatocytes following PH was markedly suppressed in LS3
      KO mice with reduced cyclinD1 transcript. However, liver mass recovered
      sufficiently following PH in LS3-KO mice almost equal to that of control mice.
      Analysis of hepatocellular growth revealed that cell size following hepatectomy
      was significantly larger in LS3-KO mice than in control mice. Hepatectomy induced
      immediate but transient phosphorylation of Akt, p70S6K, mTOR and GSK-3beta in LS3
      KO mice much more than in control mice. Additionally, adenoviral transfection of
      dominant negative mutant of Akt to control and LS3-KO mice led to insufficient
      liver regeneration following hepatectomy. CONCLUSIONS: PI3-K/Akt-mediated
      responsive hepatocellular hypertrophy may be essential for liver regeneration
      following hepatectomy and sufficiently compensated liver regeneration even in
      STAT3-deficient liver, in which cell proliferation is impaired.

PMID- 16083986
TI  - Prolonged Q-T(c) interval in mild portal hypertensive cirrhosis.
AB  - BACKGROUND/AIMS: The Q-T(c) interval is prolonged in a substantial fraction of
      patients with cirrhosis, thus indicating delayed repolarisation. However, no
      information is available in mild portal hypertensive patients. We therefore
      determined the Q-T(c) interval in cirrhotic patients with hepatic venous pressure
      gradient (HVPG) < 12 mmHg. METHODS: Forty-four patients with cirrhosis and HVPG <
      12 mmHg underwent a haemodynamic study. They were compared with 36 cirrhotic
      patients with clinically significant portal hypertension (HVPG> or = 12 mmHg) and
      controls without liver disease. RESULTS: The fraction with prolonged Q-T(c)
      interval (> 0.440 s(1/2)) was similar in the two cirrhotic groups (49 vs 50%, ns)
      and significantly above that of the controls (5%, P < 0.005). Q-T(c) was normal
      in patients with normal HVPG. Likewise, mean Q-T(c) was 0.449 and 0.447 s(1/2) in
      the two cirrhotic groups (ns), values which are significantly above that of the
      controls (0.410 s(1/2), P < 0.01). In the mild portal hypertensive group, the Q
      T(c) interval was inversely related to indicators of liver function, such as
      indocyanine green clearance (r = -0.34, P < 0.02). CONCLUSIONS: Delayed
      repolarisation of the myocardium already occurs in a substantial fraction of
      patients with cirrhosis with only a mild increase in portal pressure. The
      prolonged Q-T(c) interval may be related to liver dysfunction and to the presence
      of portal hypertension.

PMID- 16083987
TI  - The intrahepatic biliary epithelium is a target of the growth hormone/insulin
      like growth factor 1 axis.
AB  - BACKGROUND/AIMS: We evaluated the role and mechanisms by which the GH/IGF1 axis
      modulates cholangiocyte proliferation. METHODS: GH-receptors (GH-R), IGF1, IGFBP3
      (binding protein 3), IGF1-R and receptor substrates (IRS) were evaluated in
      cholangiocytes of normal or bile duct-ligated (BDL) rat livers. The effects of GH
      and IGF1 on proliferation of normal quiescent cholangiocytes and the transduction
      pathways involved were investigated. RESULTS: IGF1, GH-R, IGF1-R, IRS-1/2 were
      expressed in normal cholangiocytes and overexpressed in cholangiocytes
      proliferating after BDL which also secrete IGF1 in a higher amount than normal
      cells. IGFBP3, which may counter-regulate IGF1 effects, was decreased in BDL
      cholangiocytes. IGF1 promoted cholangiocyte proliferation in association with
      overexpression of p-IGF1R, IRS1, IRS-2, p-ERK1/2 and p-AKT. GH induced IGF1
      expression and release in isolated cholangiocytes, and reproduced the effects of
      IGF1 but GH effects were abolished by IGF1-R blocking antibody, suggesting IGF1
      as a mediator of GH. Finally, IGF1 and 17beta-estradiol reciprocally potentiated
      their proliferative effects on cholangiocytes, and by interacting at both
      receptor and post-receptor levels. CONCLUSIONS: Cholangiocytes respond to GH with
      production and release of IGF1 that modulates cell proliferation by transduction
      pathways involving IGF1-R, IRS1/2 and both ERK and PI3-kinase pathways. The
      biliary epithelium is a target of GH/IGF1 liver axis.

PMID- 16083988
TI  - Studies on the targeted delivery of the antifibrogenic compound mycophenolic acid
      to the hepatic stellate cell.
AB  - BACKGROUND/AIMS: Hepatic stellate cell (HSC) activation and proliferation are key
      events in the pathology of liver fibrosis. Inhibiting these parameters,
      therefore, is a relevant option to treat liver fibrosis pharmacologically. The
      immunosuppressive drug mycophenolic acid (MPA) has been shown to inhibit
      proliferation and activation of various types of fibroblasts. In an effort to
      circumvent the immunosuppression and at the same time enhance this antifibrotic
      effect, we coupled MPA to the HSC-selective drug carrier mannose-6-phosphate
      modified human serum albumin and evaluated this conjugate for its specificity and
      antifibrotic activity. METHODS/RESULTS: We found that MPA inhibited proliferation
      of HSC in vitro. The drug coupled to the drug carrier bound specifically to HSC
      and reduced HSC proliferation in vitro. In vivo studies demonstrated that our
      conjugate accumulated selectively in the liver with significant uptake in HSC
      apart from Kupffer and endothelial cells, whereas primary and secondary lymphoid
      tissues were avoided. Treatment of bile duct-ligated rats with this conjugate
      reduced hepatic inflammation and hepatic alpha-beta-Crystallin mRNA expression, a
      marker for HSC activation. CONCLUSIONS: This study shows that targeted delivery
      of MPA to HSC results in a decrease in HSC activation, making it the first drug
      that is successfully delivered to this cell type.

PMID- 16083989
TI  - Pathways for the regulation of body iron homeostasis in response to experimental
      iron overload.
AB  - BACKGROUND/AIMS: Secondary iron overload is a frequent clinical condition found
      in association with multiple blood transfusions. METHODS: To gain insight into
      adaptive changes in the expression of iron genes in duodenum, liver and spleen
      upon experimental iron overload we studied C57BL/6 mice receiving repetitive
      daily injections of iron-dextran for up to 5 days. RESULTS: Iron initially
      accumulated in spleen macrophages but with subsequent increase in macrophage
      ferroportin and ferritin expression its content in the spleen decreased while a
      progressive storage of iron occurred within hepatocytes which was paralleled by a
      significant increase in hepcidin and hemojuvelin expression. Under these
      conditions, iron was still absorbed from the duodenal lumen as divalent metal
      transporter-1 expressions were high, however, most of the absorbed iron was
      incorporated into duodenal ferritin, while ferroportin expression drastically
      decreased and iron transfer to the circulation was reduced. CONCLUSIONS:
      Experimental iron overload results in iron accumulation in macrophages and later
      in hepatocytes. In parallel, the transfer of iron from the gut to the circulation
      is diminished which may be referred to interference of hepcidin with ferroportin
      mediated iron export, thus preventing body iron accumulation.

PMID- 16083990
TI  - Hepatitis C virus core protein exerts an inhibitory effect on suppressor of
      cytokine signaling (SOCS)-1 gene expression.
AB  - BACKGROUND/AIMS: Suppressor of cytokine signaling (SOCS)-1, a negative feedback
      regulator of cytokine signaling pathway, also has a tumor suppressor activity,
      the silencing of its gene by hypermethylation is suggested to contribute to
      hepatocarcinogenesis. We studied the effect of the core protein of hepatitis C
      virus (HCV) on the expression of SOCS-1 gene. METHODS: HCV core gene transgenic
      mice, which develop hepatocellular carcinoma late in life, HepG2 cells expressing
      the core protein, and human liver tissues were analyzed. RESULTS: The expression
      of SOCS-1 gene was significantly suppressed in the liver of core gene transgenic
      mice and HepG2 cells expressing the core protein, while that of SOCS-3 gene was
      conserved. SOCS-1 expression levels also decreased in HCV-positive human liver
      tissues. The core protein differentially down-regulated the expression of signal
      transducer and activator of transcription (STAT) target genes, but rather
      enhanced STAT1 and STAT3 activation after interleukin-6 stimulation in mouse
      liver tissues and cells. CONCLUSIONS: HCV core protein down-regulates the
      expression of SOCS-1 gene. This is a mechanism leading to SOCS-1 silencing, an
      alternative to the hypermethylation of the gene; this effect of the core protein
      may modulate the intracellular signaling pathway, contributing to the
      pathogenesis in HCV infection including hepatocarcinogenesis.

PMID- 16083991
TI  - Cell cycle arrest and apoptosis induction in hepatocellular carcinoma cells by
      HMG-CoA reductase inhibitors. Synergistic antiproliferative action with ligands
      of the peripheral benzodiazepine receptor.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the fifth most common cause of
      cancer deaths worldwide. Inhibitors of cholesterol biosynthesis ('statins') have
      been proposed as promising adjunctive anticancer agents to treat HCC, but their
      mode of action is yet poorly characterized. We additionally investigated the
      potential benefit of a combination of peripheral benzodiazepine receptor (PBR)
      ligands and statins. METHODS: We analyzed the growth inhibitory effects of PBR
      ligands, statins, and their combination in two human HCC cell lines. Moreover, we
      investigated the regulation of cellular cholesterol levels and the expression of
      3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMG-CoAR), the target of
      statins. RESULTS: Statins inhibited the proliferation of HCC cells by inducing
      apoptosis and G1/S cell cycle arrest. Statin-induced apoptosis was characterized
      by a breakdown of the mitochondrial membrane potential, caspase activation and
      nuclear degradation. Furthermore, activation of ERK1/2 was downregulated while
      p38MAPK was activated. Synergistic growth inhibition was obtained by the
      combination of the PBR ligand FGIN-1-27 with statins. PBR ligands induced a
      decrease of HMG-CoAR expression. This downregulation may be responsible for the
      enhanced sensitivity of HCC cells to statins. CONCLUSIONS: Our data shed light on
      the signaling cascades mediating statin-induced growth inhibition of HCC cells.
      Moreover, PBR ligands sensitized HCC cells to statins, suggesting a new strategy
      to treat HCC.

PMID- 16083992
TI  - Hippocampal NMDA receptor subunit expression and watermaze learning in estrogen
      deficient female mice.
AB  - The aromatase knockout (ArKO) mouse is estrogen deficient. Using reverse
      transcription and real-time PCR, we showed that transcript levels of the N-methyl
      d-aspartate (NMDA) receptor subunit NR2B are significantly higher in the
      hippocampus of female ArKO mice compared to wild-type (WT) littermates.
      Expression levels of NR1, NR2A, but not NR2C, also tended to be higher in ArKO
      mice. In the Morris watermaze test for spatial memory, both genotypes displayed
      equal significant improvement in the latency in locating the invisible platform
      over the 5-day training period. These findings show that selective loss of
      estrogen synthesis is associated with changes in NMDA receptor subunit expression
      in the hippocampus but little change in spatial learning ability.

PMID- 16083993
TI  - Obesity-associated mutations in the melanocortin 4 receptor provide novel
      insights into its function.
AB  - Mutations in the Melanocortin 4 receptor are implicated in 1-6% of early onset or
      severe adult obesity cases. Most of the patients carry heterozygous missense
      mutations. Arguments for the pathogenicity of these mutations are based on the
      frequency of rare functionally relevant non-synonymous mutations in severely
      obese children and adults versus non-obese controls, the segregation of mutations
      with obesity in the family of the probands (although with incomplete penetrance)
      and the relevant functional defects described for these mutations. We have
      developed new assays to study the functional characteristics of these obesity
      associated MC4R mutations. Systematic and comparative functional study of over 50
      different obesity-associated mutations suggests that multiple functional
      alterations contribute to their pathogenicity. These studies also lead to new
      insights into the structure-function relationship of MC4R, provide novel
      hypotheses for the genetic predisposition to common obesity in humans and allow
      the development of new molecular tools for studying the physiological role of
      GPCRs.

PMID- 16083994
TI  - [Primary and atypical facial pain: diagnosis and treatment].
AB  - PURPOSE: Facial pain is a frequently encountered symptom in general medical
      practice and encompass a wide group of facial problems. As correct diagnosis can
      usually be reached by history and physical examination for well defined typical
      clinical entities (trigeminal neuralgia, cluster headache) atypical facial pain
      may have many other potential causes (sinuses infection, temporomandibular joint
      syndrome, dental disorders...) so that diagnosis not appear an easy task. CURRENT
      KNOWLEDGE AND KEYPOINTS: Anatomical and physiological organization of facial
      nociceptive system, particularly trigeminal system, may explain the variability
      of facial pain. Although symptoms have been clearly identified mechanism of pain
      production remains controversial. Several factors (psychological, neurological,
      endocrine...) and mechanisms (neuropathic, vascular, myoarticular) may coexist
      and explain trouble in diagnosing and treating facial pain. FUTURE PROSPECTS AND
      PROJECTS: Better knowledge in identifying the cause of facial pain may lead to
      improve patient care and avoid patient frustration, medical nomadism, repetitive
      dental and otolaryngologic procedures, and finally non-compliance with treatment.

PMID- 16083995
TI  - Severe hyperkalemia associated with "alternative" nutritional cancer therapy.

PMID- 16083996
TI  - Does growth hormone allow more efficient nitrogen sparing in postoperative
      patients requiring parenteral nutrition? A double-blind, placebo-controlled
      randomised trial.
AB  - BACKGROUND & AIMS: Growth hormone (GH) has a strong anabolic effect and is
      thought to be useful in improving the efficacy of parenteral nutrition (PN) to
      preserve muscle mass (MM) in the postoperative setting. Unfortunately, the
      negative clinical outcome of GH treatment in intensive care patients limits its
      use in this setting, but demands answers to the mechanism behind the action of
      this therapy. METHOD: In a double-blind randomised controlled study consecutive
      patients after major abdominal surgery were divided into four groups of either
      1/2-PN (0.13 g N/kg/day and 52% of calories as lipid) or full-strength PN (Full
      PN) (0.3 g N/kg/day and 65% of calories as lipid) receiving daily injections of
      either GH (8-16 IU) or placebo for a period of 14 days postoperative. Outcome
      measures included MM derived from measures of total body potassium (40K counting)
      and total body nitrogen (TBN) (in vivo neutron capture technique); Fat mass from
      skin folds; serum insulin like growth factor-I (IGF-I) and its binding proteins
      (IGFBP). RESULTS: From 43 major upper GI surgical patients randomised 35
      completed the study (one patient died from sepsis in the half-strength PN (1/2
      PN)+GH group). 1/2-PN (n=11) lost TBN (P=0.001), MM (P=0.005) but not fat. Full
      PN (n=9) maintained TBN, MM (P=0.056) and fat. 1/2-PN+GH (n=8) maintained TBN and
      fat but lost MM (P=0.038). Full-PN+GH (n=7) maintained TBN and MM but lost fat
      (P=0.018). Two-way ANOVA indicated that PN input (P=0.031) and not GH had a
      significant effect on MM. GH caused a significant rise in IGF-I levels (290+/-67
      and 454+/-71 microg/l for 1/2-PN+GH and Full-PN+GH, respectively) and restored
      serum IGFBP3 and the acid labile subunit to normal, by the postoperative day 9.
      CONCLUSION: After major gastrointestinal surgery, GH causes a marked hepatic IGF
      I response and nitrogen retention but its effect on body composition was more
      significant with a high PN input. Further, Full-PN alone was sufficient to
      prevent nitrogen loss and preserved MM and addition of GH does not provide
      further metabolic advantage.

PMID- 16083997
TI  - Reduction of external dose in a wet-contaminated housing area in the Bryansk
      Region, Russia.
AB  - An investigation of the feasibility of reducing the external dose rate in a
      recreational housing area located between the settlements of Guta and Muravinka,
      Bryansk Region, Russia, which had been contaminated by the Chernobyl accident
      more than a decade earlier was made. Removal of contaminated topsoil was carried
      out over an area of about 2000 m2, optimising the thickness of the removed layer
      according to an assessment of the vertical contaminant distribution. A layer of
      clean sand was applied to shield against radiation from residual contamination in
      the ground. Careful monitoring of dose rates in reference positions showed that
      this could reduce the dose rate outdoors by about a factor of 6. The replacement
      of a roof was found to reduce the dose rate considerably inside the house. A cost
      analysis of the operation is presented.

PMID- 16083998
TI  - Urban dose rates at Gavle, Goteborg and Lund.
AB  - Besides gamma rays from 137Cs emanating from the Chernobyl accident, gamma rays
      from natural radionuclides are a dominant source of radiation exposure to the
      public. Since people spend much more time indoors than outdoors the radiation
      dose obtained inside dwellings contributes greatly to individual and collective
      doses. Dose rate measurements were made at 20 locations within the city of
      Goteborg and at further 22 reference sites within a radius of 100 km.
      Measurements were also made at Gavle and Lund. The dose rates were measured with
      RNI intensimeters, TLD (LiF) meters and in in situ measurements using an HPGe.
      The ground cover was grass, asphalt, concrete slates or paving-stones. The dose
      rates varied between 0.05 and 0.25 microSv/h. Also performed in different ways,
      measurements made inside and outside buildings at both Goteborg and Gavle showed
      inside dose rates higher than outside dose rates.

PMID- 16083999
TI  - On monitoring anthropogenic airborne uranium concentrations and (235)U/(238)U
      isotopic ratio by Lichen - bio-indicator technique.
AB  - Lichens are widely used to assess the atmospheric pollution by heavy metals and
      radionuclides. However, few studies are available in publications on using
      lichens to qualitatively assess the atmospheric pollution levels. The paper
      presents research results applying epiphytic lichens as bio-monitors of
      quantitative atmospheric contamination with uranium. The observations were
      conducted during 2.5 years in the natural environment. Two experimental sites
      were used: one in the vicinity of a uranium contamination source, the other one -
      at a sufficient distance away to represent the background conditions. Air and
      lichens were sampled at both sites monthly. Epiphytic lichens Hypogimnia physodes
      were used as bio-indicators. Lichen samples were taken from various trees at
      about 1.5m from the ground. Air was sampled with filters at sampling stations.
      The uranium content in lichen and air samples as well as isotopic mass ratios
      (235)U/(238)U were measured by mass-spectrometer technique after uranium pre
      extraction. Measured content of uranium were 1.45 mgkg(-1) in lichen at 2.09 E-04
      microgm(-3) in air and 0.106 mgkg(-1) in lichen at 1.13 E-05 microgm(-3) in air.
      The relationship of the uranium content in atmosphere and that in lichens was
      determined, C(AIR)=exp(1.1 x C(LICHEN)-12). The possibility of separate
      identification of natural and man-made uranium in lichens was demonstrated in
      principle.

PMID- 16084000
TI  - Relationships and bioaccumulation of chemical elements in the Baikal seal (Phoca
      sibirica).
AB  - Concentrations of Al, Ba, Cd, Cu, Fe, Mn, Mo, Si, Sr, Zn, Ca, K, Mg, Na and P in
      the livers of Baikal seal, plankton, zoobenthos, and fish, constituting the food
      sources for the seals, were determined by ICP-MS and ICP-AES. The accumulation of
      elements in the liver of seals, affected by internal and external (environmental)
      factors, was assessed by multidimensional (ANOVA, FA) and correlation analyses.
      FA has enabled identification of abiotic and biotic factors responsible for the
      accumulation of elements in the livers of Baikal seals. Significant influence of
      sex and development stage of the seals analysed on hepatic concentrations of some
      elements was found. The observed differences in element concentrations between
      pups, males and females could be attributable to the reproductive cycle of this
      species. ANOVA showed differences in concentrations of Fe, Zn, Cu and Cd in seals
      from the three separate basins of the lake. BMFs suggest biomagnification of Fe
      and Zn in the fish-seal trophic link.

PMID- 16084001
TI  - Effects of teflubenzuron on sediment processing by members of the Capitella
      species-complex.
AB  - The cosmopolitan deposit-feeding polychaete Capitella is widely used as an
      indicator of organic pollution and plays an important role in waste recycling at
      aquaculture sites. Teflubenzuron is currently employed by salmon farms as an in
      feed compound to control ectoparasite infestations. Its occurrence in sediments
      could pose a hazard to local sediment infauna. A bioassay to investigate the
      effects of exposing Capitella sp I and Capitella sp B to sediment spiked with
      environmentally relevant concentrations of teflubenzuron (8.4, 25 and 41.8
      microg/g dry wt. sediment) is described. No mortality was recorded for Capitella
      sp I, but increasing teflubenzuron concentrations significantly reduced egestion
      rates. Capitella sp B exhibited mortality, although egestion was not affected.
      These results using Capitella spp. indicated that teflubenzuron could affect the
      rate of sediment processing by polychaetes close to fish farms treated with this
      compound. Further studies are recommended to assess the potential of contaminants
      in aquaculture wastes.

PMID- 16084002
TI  - Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate
      reductase gene with schizophrenia: association is significant in men but not in
      women.
AB  - Schizophrenia is a complex and common psychiatric disorder with a polygenic
      inheritance. In our previous report, we showed an association between the
      methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms
      and schizophrenia in patients from Bakirkoy in Istanbul, Turkey [Sazci, A.,
      Ergul, E., Guzelhan, Y., Kaya, G., Kara, I., 2003. Methylenetetrahydrofolate
      reductase gene polymorphisms in patients with schizophrenia. Mol. Brain Res. 117,
      104-107]. We wanted also independently to confirm this study in a gender-specific
      manner with schizophrenic patients from Erenkoy in Istanbul, Turkey. To
      investigate the role of the C677T and A1298C polymorphisms of
      methylenetetrahydrofolate reductase gene in schizophrenia in a gender-specific
      manner, we analyzed the genotypes of MTHFR677 and MTHFR1298 of 297 schizophrenic
      patients and 341 healthy controls, using a polymerase chain reaction restriction
      fragment length polymorphism method. The MTHFR 677T allele was significantly
      distributed (chi2=7.312; P=0.026), between schizophrenic patients and healthy
      controls. The T677T genotype was overrepresented in the total schizophrenic
      patients (OR=1.938; 95%CI=1.133-3.315; chi2=5.996; P=0.014). Similarly, the
      T677T/A1298A compound genotype was the most significant one in the total
      schizophrenic patients (OR=2.397; 95% CI=1.327-4.330; chi2=8.821; P=0.003). The
      C1298C genotype was overrepresented in the total schizophrenic patients
      (OR=1.706; 95%CI=1.014-2.870; chi2=4.126; P=0.042). Likewise, the C677C/C1298C
      compound genotype was significant in the total schizophrenic patients (OR=1.689;
      95%CI=0.985-2.894; chi2=3.695; P=0.055). When schizophrenic patients and healthy
      controls were stratified according to gender difference, the T677T genotype and
      T677T/A1298A compound genotype were significantly overrepresented (OR=2.184; 95%
      CI=1.069-4.462; chi2=4.767; P=0.029; OR=2.748; 95% CI=1.215-6.214; chi2=6.301;
      P=0.012, respectively) in men schizophrenic patients. However, neither the MTHFR
      C677T nor the A1298C polymorphisms are associated with schizophrenia in women. In
      conclusion, the MTHFR 677T allele and T677T, C1298C genotypes, and T677T/A1298A,
      C677C/C1298C compound genotypes are genetic risk factors for schizophrenia in men
      but not in women in a gender-specific manner.

PMID- 16084003
TI  - [Study of the morphologic variations of the scaphocephaly. Deduction for their
      systematisation].
AB  - PURPOSE: The scaphocephaly is the most frequent craniosynostosis secondary to a
      premature synostosis of the sagittal suture. Despite this univocal pathogeny
      there are a great heterogeneity in the skull deformation and their
      systematisation stay imprecise. The aim of this study was to analyse the
      different morphology of the scaphocephaly by 3D CT-scan to clarify the different
      shapes. MATERIAL AND METHODS: This retrospective study was done from the
      morphometric analysis of forty-two 3D CT-scan (10 girls and 32 boys). The
      scaphocephaly was classified in two groups according to the systematisation of
      Stricker and Montaut: the sphenocephaly (large forehead) and the leptocephaly
      (narrow forehead). The variation of the calvaria shape was analysed and different
      index were calculated. RESULTS: There were 30 sphenocephaly and 12 leptocephaly.
      Excepted for the forehead deformation there was a morphometric difference of the
      occipital pole that was backward rotated in the leptocephaly. In the two groups
      there were retro-coronal constriction (40.5%) or pre-lambdoid constriction (9.5%)
      independently of the sagittal synostosis degree. CONCLUSIONS: The morphometric
      analysis shows that the deformation of the skull secondary to the premature
      synostosis of the sagittal suture can be different. The adaptative defect of the
      metopic suture can be to explain this difference. This deformation can be
      harmonious, or with a retro-coronal constriction resulting in a bitemporal
      narrowing, or with a pre-lambdoid constriction resulting in an occipital chignon.
      These results conduce to qualify the surgical correction to adapt at the
      different shapes.

PMID- 16084004
TI  - Medical aspects of sulphur mustard poisoning.
AB  - Sulphur mustard is one of the major chemical warfare agents developed and used
      during World War I. Large stockpiles are still present in several countries. It
      is relatively easy to produce and might be used as a terroristic weapon. Sulphur
      mustard is a vesicant agent and causes cutaneous blisters, respiratory tract
      damage, eye lesions and bone marrow depression. The clinical picture of poisoning
      is well known from the thousands of victims during World War I and the Iran-Iraq
      war. In the latter conflict, sulphur mustard was heavily used and until now about
      30,000 victims still suffer from late effects of the agent like chronic
      obstructive lung disease, lung fibrosis, recurrent corneal ulcer disease, chronic
      conjunctivitis, abnormal pigmentation of the skin, and several forms of cancer.
      Despite enormous research efforts during the last 90 years, no specific sulphur
      mustard antidote has been found. The prospering knowledge and developments of
      modern medicine created nowadays new chances to minimize sulphur mustard-induced
      organ damage and late effects.

PMID- 16084005
TI  - Towards the creation of an international toxicology information centre.
AB  - A pilot toxicology database system has been created which is accessible on-line
      via the world-wide web or in-house via an intranet. It is intended to be suitable
      as a source of toxicological information and to support structure-activity
      relationship studies, and it can be searched on chemical structural and
      substructural as well as toxicological and physico-chemical data. Successful
      completion of the pilot has led to an ongoing project to develop and expand the
      system.

PMID- 16084006
TI  - Effects of reproductive state on olfactory sensitivity suggest odor specificity.
AB  - Previous studies of reproductive state and olfactory sensitivity in women have
      not directly compared thresholds for social and environmental odors. Here, we
      used successive dilutions presented in a staircase protocol to determine
      olfactory thresholds for androstadienone, a social odor produced by men, and
      rose, an environmental odor signaling a source of micronutrients essential for
      successful implantation, prenatal development and maternal health. Fertile women
      were more sensitive to the social than the environmental odor, while women using
      oral contraceptives, a non-fertile hormonal state similar to early pregnancy,
      were more sensitive to the environmental odor. This preliminary study sets the
      stage for further work on the interaction between hormonal states and sensitivity
      to specific odors with reproductive significance.

PMID- 16084007
TI  - Spin-dependent absorption of water molecules.
AB  - The effects of spin state of water molecules on its absorption on lyophilized
      DNA, lysozyme and some inorganic sorbents were studied. It was shown that the
      absorption rates of ortho and para water from vapor differ noticeably. The para
      isomer binding with preparations is distinctly faster than that of the ortho
      isomer in all cases. Clear-cut distinction in the sorption kinetics is determined
      by the difference in quantum statistics for spin isomers, which in its turn can
      give rise to remarkable differences in physico-chemical properties of ortho and
      para water. This finding opens a wide field of activity in studying fundamental
      and applied problems relating to the role of the spin state of water molecules in
      physics, chemistry, biology and medicine.

PMID- 16084008
TI  - Prognostic parameters other than Gleason score for the daily evaluation of
      prostate cancer in needle biopsy.
AB  - OBJECTIVE: To evaluate in prostate needle biopsies the usefulness and the
      efficacy of not time-consuming morphologic parameters in order to predict whether
      prostate cancer is organ-confined or it is not, that could contribute additional
      information to pre-surgical serum PSA and Gleason score, both of them parameters
      already accepted as clinically significant. METHODS: Three hundred and two
      consecutive patients were evaluated, of whom a diagnostic needle biopsy and the
      radical prostatectomy specimen with no pre-surgical hormone therapy were
      available. Bilateral or unilateral extension, number of positive cores,
      percentage of positive cores, intraprostatic perineural invasion (IPNI) and the
      presence of high-grade prostatic intraepithelial neoplasia (HGPIN) in any of the
      biopsy cores were evaluated in the needle biopsy. RESULTS: The median of cores is
      6. The IPNI, the presence of bilateral tumour, and the percentage of positive
      cores, higher than 37.5% (ROC curve), show significant crude OR (4.0, 2.8, 6.9
      respectively). The regression model discloses that only the percentage of
      positive cores shows a significant OR (5.8) adjusting for bilaterality, IPNI,
      HGPIN and age. CONCLUSIONS: The percentage of cores with cancer and the bilateral
      involvement are another two parameters predictive of cancer with extraprostatic
      extension. (p<0.0005 in both). IPNI has statistical significance too (p<0.002),
      but it is related to the tumour volume expressed through the two mentioned
      parameters.

PMID- 16084009
TI  - Activity of angiotensin peptides in clitoral cavernosum of alloxan induced
      diabetic rabbit.
AB  - OBJECTIVES: To assess the role of peptides of the angiotensin (ANG) on the
      regulation of clitoral cavernosum tone and changes in ANG binding affinity in the
      rabbit with diabetes mellitus. MATERIAL AND METHODS: The isometric tension
      measurement and in vitro autoradiography were used in sham and diabetic clitoral
      cavernosum. RESULTS: In tension study, contractility in response to ANG I, ANG
      II, ANG III and ANG IV was enhanced in diabetic clitoral cavernosum strips (EC50
      was 67.6 +/- 27.2, 4.3 +/- 0.4, 189.3 +/- 37.3, 443.2 +/- 0.4 nM for diabetic
      versus 155.2 +/- 76.1, 38.3 +/- 0.1, 528.0 +/- 75.2, 616.9 +/- 69.5 nM for sham,
      respectively). Contractile responses to ANG II was significantly inhibited by
      type 1 ANG II receptor (AT1) antagonist but not by type 2 ANG II receptor (AT2)
      antagonist in both groups. Percentages in contractions by ANG II (1 nM) in the
      presence of Dup 753 decreased significantly 36.2 +/- 4.6 to 6.3 +/- 2.4% in sham
      and 56.1 +/- 7.7 to 6.0 +/- 4.8% in diabetic group. The binding affinities were
      enhanced in diabetic clitoral cavernosum for ANG II (dissociation constant, 4.9
      +/- 1.0 for sham versus 0.9 +/- 0.2 nM for diabetic) and for ANG I, ANG III, and
      ANG IV (inhibitory constant, 28.6 +/- 1.5, 398.7 +/- 157.2, and 3966.5 +/- 1524.1
      nM for sham versus 20.6 +/- 5.7, 78.5 +/- 23.7, and 1098.7 +/- 195.5 nM, for
      diabetic, respectively, all p < 0.05). Sensitivities of AT1 and AT2 receptors to
      ANG II enhanced in diabetic than sham clitoral cavernosum tissue. CONCLUSIONS:
      This results suggest that the contractile responses to all four ANG peptides are
      enhanced in the diabetic clitoral cavernosum. Enhancement of contractility in
      diabetic clitoral cavernosum may be related to the increased affinity to ANG II
      receptors for ANG peptides.

PMID- 16084010
TI  - Pattern of relapse after first line treatment of advanced stage germ-cell tumors.
AB  - OBJECTIVES: We performed a retrospective analysis of first relapses after
      cisplatin-based chemotherapy in patients with advanced germ-cell tumors, in order
      to better define the appropriate follow-up. METHODS: These patients were treated
      between 1986 and 1998 in two institutions. They were either followed after first
      line chemotherapy at the same center or referred for relapse. RESULTS: Ninety-six
      patients relapsed (17.5% of the total number of patients treated in the same time
      period). Thirty-five (36.4%) patients had serum tumor marker levels (AFP, hCG and
      LDH) normal values. Sites of relapse were: abdominal in 47 (49%) patients,
      thoracic in 17 (17.7%), thoraco-abdominal in 15 (15.6%), and brain in 8 (8.3).
      Seven (7.3%) patients had elevated markers only, 1 (1%) had isolated supra
      clavicular lymph node, 1 (1%) had bone metastasis only. Eighty-two patients (85%)
      relapsed during the first 18 months of follow-up. All patients with brain
      metastases at relapse and those who obtained sCR after chemotherapy relapsed
      within 8 months of follow-up. Sixteen patients underwent resection of growing
      teratoma. CONCLUSIONS: These results allow to recommend extensive follow-up
      during the first two years after response to first line treatment. It includes
      marker level determination and whole body CT scan and less intensive work-up
      there after.

PMID- 16084011
TI  - Nek2 kinase in chromosome instability and cancer.
AB  - Aneuploidy and chromosome instability are two of the most common abnormalities in
      cancer cells. They arise through defects in cell division and, specifically, in
      the unequal segregation of chromosomes between daughter cells during mitosis. A
      number of cell cycle dependent protein kinases have been identified that control
      mitotic progression and chromosome segregation. Some of these localize to the
      centrosome and regulate mitotic spindle formation. One such protein is Nek2, a
      member of the NIMA-related serine/threonine kinase family. Data are emerging that
      Nek2 is abnormally expressed in a wide variety of human cancers. In this review,
      we summarize current knowledge on the expression, regulation and function of
      Nek2, consider how Nek2 may contribute to chromosome instability, and ask whether
      it might make an attractive target for chemotherapeutic intervention in human
      cancer.

PMID- 16084012
TI  - Signaling regulation of genomic and nongenomic functions of estrogen receptors.
AB  - Estrogen receptors (ERs) mediate the effects of 17beta-estradiol under
      physiologic and pathologic conditions. ERs trigger 17beta-estradiol-sensitive
      gene transcription by binding to specific estrogen response elements (i.e.
      genomic mechanism). The cellular effects of estrogen are also influenced by
      membrane- or cytoplasm-initiated responses (i.e. nongenomic mechanism). Both ER
      evoked genomic and nongenomic effects originate from a unique signaling network.
      Furthermore, estrogen-initiated rapid pathways and ERalpha interactions with
      specific partners (e.g. AIB1, PELP1/MNAR; MTA1, MTA1s and p130Cas) influence both
      ER functions. Here, we summarize the recent findings related to multiple
      regulatory levels of the signaling networks responsible for ERs-mediated
      responses in breast cancer cells.

PMID- 16084013
TI  - Significance of vascular stabilization for tumor growth and metastasis.
AB  - This mini review highlights the role of vascular stabilization which is
      apparently mediated by factors belonging to both the pro- and anti-angiogenic
      group. Knowingly angiopoietin-1 has pro-angiogenic properties while endostatin
      acts anti-angiogenic. But both factors suppress tumor growth in experimental
      tumor models. The crossing points of mechanisms of their action are the
      parameters vascular stabilization and vascular permeability, which are of high
      importance not only for tumor vascularization, but also for tissue
      vascularization in general. Both angiopoietin-1 and endostatin reduce the
      vascular permeability, but promote vascular stabilization. Vascular stabilization
      is significantly increased under experimental treatment of tumors with
      angiogenesis inhibitors such as endostatin. It inhibits tumor growth and probably
      tumor metastasis. The understanding of temporal and spatial sequences of vascular
      stabilization is an important challenge for scientists working on tumor
      vascularization and anti-angiogenic tumor therapy.

PMID- 16084014
TI  - Electroenzymatic degradation of azo dye using an immobilized peroxidase enzyme.
AB  - Azo dyes are largely resistant to biodegradation and persist in conventional
      wastewater treatment processes. Combining enzymatic catalysis and the
      electrochemical generation of hydrogen peroxide (H2O2), an electroenzymatic
      process was developed, which is a potential alternative to traditional processes.
      In this study, an electroenzymatic method that uses an immobilized horseradish
      peroxidase enzyme (HRP), was investigated to degrade orange II (azo dye) within a
      two-compartment packed-bed flow reactor. To evaluate the electroenzymatic
      degradation of orange II, electrolytic experiments were carried out with 0.42
      U/mL HRP at -0.5 V. It was found that removal of orange II was partly due to its
      adsorption to the graphite felt. The overall application of the electroenzymatic
      led to a greater degradation rate than the use of electrolysis alone. Also the by
      products formed were found to consist primarily of an aromatic amine, sulfanilic
      acid, and unknown compounds.

PMID- 16084015
TI  - Influence of variables of the combined coagulation-Fenton-sedimentation process
      in the treatment of trifluraline effluent.
AB  - The effluent stream from the industrial production of the herbicide trifluraline
      (amination water) was submitted to a combined treatment of a physical-chemical
      process (coagulation) with an advanced oxidation process (Fenton). The recovering
      of the residual sludge was performed. The combined coagulation-Fenton
      sedimentation process proved to be very suitable for wastewater color reduction
      (91.6%), promoting considerable abatement of the organic load (63.4% COD
      reduction). According to the fractionary factorial design, the main effects of pH
      (A) and Fenton sludge (B) variables were considered statistical fluctuations of
      the process (and not decisive), while the main effects of Fe(3+) (C), Fe(2+) (D)
      and H(2)O(2) (E), as well as the interactions between variables A and B, A and E,
      C and D and C and E were considered significant. The obtained results suggest
      that the combined process can be advantageous for the treatment of recalcitrant
      industrial effluents, such as the amination water from the trifluraline
      production.

PMID- 16084016
TI  - Explosive properties of 1-hydroxybenzotriazoles.
AB  - 1-hydroxybenzotriazole and its derivatives are widely used as peptide coupling
      reagents. However, people are often not aware that such compounds show explosive
      properties when heated under defined confinement or when subjected to mechanical
      stimulus. 1-Hydroxybenzotriazole (HOBt) is able to propagate a detonation when a
      stronger booster is used. Sometimes explosive substances are desensitized to
      suppress their hazardous properties, yet depending on the amount and nature of
      desensitizer, the result is often not quite satisfactory. During the last years,
      some 1-hydroxybenzotriazoles were tested at BAM. The results are presented in
      this paper.

PMID- 16084017
TI  - Intracisternal administration of mitogen-activated protein kinase inhibitors
      reduced IL-1beta-induced mirror-image mechanical allodynia in the orofacial area
      of rats.
AB  - The present study investigated the role of central mitogen-activated protein
      kinases (MAPKs) in interleukin-1beta (IL-1beta)-induced mirror-image mechanical
      allodynia in the orofacial area. Experiments were carried out on Sprague-Dawley
      rats. Under pentobarbital sodium anesthesia, a polyethylene tube was implanted in
      the subcutaneous area of one vibrissa pad, which enabled us to inject IL-1beta.
      For an intracisternal injection, each anesthetized rat was mounted on a
      stereotaxic frame and a polyethylene tube was implanted. Animals were given a
      recovery time of at least 72 h from surgery. After a subcutaneous administration
      of 0.01, 0.1, 1, or 10 pg of IL-1beta, we examined the face withdrawal behavioral
      responses produced by 10 successive trials of air puffs ipsilateral or
      contralateral to the IL-1beta injection site. Normal animals did not respond to
      pressure less than 40 psi. The thresholds of air puffs ipsilateral and
      contralateral to the IL-1beta injection site were significantly lower in the IL
      1beta-treated group, compared with the vehicle-treated group. The decrease in the
      threshold of air puffs appeared 10 min after an IL-1beta injection and persisted
      for over 3h. Intracisternal pretreatment with PD98059, a p44/42 MAPK inhibitor,
      or SB203580, a p38 MAPK inhibitor, significantly reduced the decrease in the
      threshold of air puffs ipsilateral to the IL-1beta injection site produced by 10
      pg of IL-1beta. IL-1beta-induced mirror-image mechanical allodynia was also
      reduced significantly by intracisternal pretreatment with both PD98059 and
      SB203580. These results indicate that central MAPK pathways mediate IL-1beta
      induced mirror-image mechanical allodynia in the orofacial area.

PMID- 16084018
TI  - Cardiotrophin-1 protects cortical neuronal cells against free radical-induced
      injuries in vitro.
AB  - Cardiotrophin-1 (CT-1) was initially defined as a mediator of cardiomyocyte
      hypertrophy. Additional studies have showed that CT-1 enhanced survival of
      differentiated cardiac muscle cells and inhibited cardiac myocyte apoptosis after
      serum deprivation or cytokine stimulation. Moreover, CT-1 has recently been shown
      to act as a neuroregulatory cytokine in the peripheral nervous system. However,
      its effects in the central nervous system have not been determined. In the
      present study, we evaluated whether CT-1 protects cultured cortical neurons
      against oxidative injuries caused by the hydroxyl radical-producing agent FeSO4
      and by the peroxynitrite-producing agent 3-morpholinosydnonimine (SIN-1). CT-1
      reduced neuronal cell death caused by FeSO4 and also attenuated the neurotoxic
      effect of SIN-1 in a dose-dependent manner. These results indicate that CT-1 is
      neuroprotective in an in vitro model of cerebral ischemia. This study indicates
      that further evaluation of CT-1 in acute brain injury should be investigated in
      vivo.

PMID- 16084019
TI  - Bax-regulated mitochondria-mediated apoptosis is responsible for the in vitro
      ischemia induced neuronal cell death of Sprague Dawley rat.
AB  - An in vitro ischemia model was used to determine the molecular mechanisms
      responsible for the ischemia-induced neuronal cell death. Additionally, the
      neuronal protective mechanisms of anti-apoptotic drugs against ischemia were also
      evaluated. In this study, the primary neuronal cultures were incubated in an
      anoxic chamber with 95% of N2 and 5% of CO2 for various times. The death rate,
      degree of the apoptotic damage, reduction of mitochondrial membrane potential,
      translocation of Bax, release of cytochrome C and activation of caspase-9 and -3
      were determined at each time point. Results showed that a Bax-regulated
      mitochondria- mediated apoptosis is responsible for the in vitro ischemia-induced
      neuronal death. Reduction in mitochondrial membrane potential plays no role in
      triggering this apoptosis. Furthermore, the anti-apoptotic drugs: furosemide (a
      Bax blocker) and ZVAD-fmk (caspase inhibitor) but not cyclosporine A (a MPT pore
      blocker), significantly protected the neurons against ischemia-induced damage.
      This provides an additional consideration in the future selection of new anti
      ischemic drugs.

PMID- 16084020
TI  - Apo E genotype not associated with intravascular coagulation in traumatic brain
      injury.
AB  - There is considerable evidence linking both genotype and coagulopathy to vascular
      complications of traumatic brain injury (TBI) and other cerebral insults. The
      authors explored a possible connection between the apolipoprotein E (Apo E)
      genotype, coagulopathy and intravascular microthombosis (IMT) in TBI. The
      predicted association was not confirmed.

PMID- 16084021
TI  - Comparison of melanin-concentrating hormone and hypocretin/orexin mRNA expression
      patterns in a new parceling scheme of the lateral hypothalamic zone.
AB  - A high-resolution spatial distribution analysis of hypothalamic neurons
      expressing melanin-concentrating hormone or hypocretin/orexin was performed in
      adult male rats with in situ hybridization cytochemistry. For the analysis, a new
      parcellation of the lateral zone with some two-dozen regions was used, and
      distributions were plotted on 15 transverse reference levels through the
      hypothalamus. Qualitatively the results confirm earlier, much lower resolution
      mapping studies, although some discrepancies are clarified. Previous work
      indicates that each of these cell populations is far from homogeneous, and the
      present results should help establish a framework for clarifying more precisely
      how they are differentiated and organized in terms of axonal input-output
      relationships and gene expression patterns, and for defining precise
      relationships with other hypothalamic neuron populations.

PMID- 16084022
TI  - Expression of glycine receptor and transporter on bullfrog retinal Muller cells.
AB  - The expression of the glycine receptor (GlyR) alpha1, alpha2 and beta subunits
      and glycine transporter (GlyT) on Muller cells was studied in bullfrog retina
      using double immunofluorescence labeling and confocal scanning microscopy. Double
      labeling of glial fibrillary acidic protein (GFAP), a specific marker for Muller
      cells, and the GlyR subunits showed that almost all Muller cells moderately
      expressed GlyR alpha1 and weakly GlyR beta, whereas no immunoreactivity for GlyR
      alpha2 was observed. The labeling for GlyR alpha1 and GlyR beta appeared in
      somata, major processes, endfeet and branchlets of the Muller cells. Muller cells
      were also GlyT1-labeled. Consistent with previous electrophysiological results,
      these findings suggest that Muller cells may be involved in modulation of
      glycinergic transmission by reciprocal interactions with retinal neurons through
      GlyR and GlyT.

PMID- 16084024
TI  - Reductions in and relations between "craving" and drinking in a prospective, open
      label trial of ondansetron in adolescents with alcohol dependence.
AB  - Recently, we reported that ondansetron (a 5-HT3 antagonist) as an adjunct to
      cognitive behavioral therapy (CBT) produced significant within-group decreases
      (improvement) in drinking in adolescents with alcohol dependence. We previously
      have hypothesized that the mechanism of ondansetron treatment response in
      adolescents with alcohol dependence should be similar to early onset adult
      alcoholics, wherein blockade of serotonin-3 receptors may decrease dopamine
      release and subsequent alcohol consumption and craving. We now suggest that one
      mechanism by which ondansetron diminishes drinking in adolescents with alcohol
      dependence is through a reduction in "craving" as measured by the Adolescent
      Obsessive-Compulsive Drinking Scale (A-OCDS). We conducted an 8-week,
      prospective, open-label study of ondansetron (4 microg/kg b.i.d.) in 12
      adolescents (age 14-20 years) who had alcohol dependence. Results showed that
      "irresistibility" and total scores as measured by the A-OCDS were correlated
      significantly with drinking indices (drinks/day, percent days abstinent) at the
      end of treatment, and that "irresistibility" and total A-OCDS scores decreased
      significantly by the end of treatment. These preliminary results suggest that the
      A-OCDS can be useful as an outcome measure in clinical studies of adolescents
      with alcohol dependence.

PMID- 16084025
TI  - Origin and evolution of viruses: escaped DNA/RNA sequences as evolutionary
      accelerators and natural biological weapons.
AB  - Knowledge of the origin and evolution of viruses could provide a better
      understanding of a number of phenomena in the field of evolution such as the
      origin and development of multi-cellular organisms, the rapid diversification of
      species over the last 600-700 million years and the lack of transitional forms in
      the evolution of species ("missing links") etc. One of the possible effects of
      escaped DNA/RNA sequences or viruses on the evolution of multi-cellular
      organisms, especially vertebrates, could be the phenomenon of horizontal
      transmission and dissemination of genes. Interestingly, if so, this effect could
      be considered as a model of primeval and natural genetic engineering. Other
      possible links between the evolution of multi-cellular organisms and viruses are
      connected with the fact that viruses represent the source of different forms of
      selective pressure such as epidemics of infectious diseases, autoimmunity,
      malignant alteration, reproductive efficiency, etc. At the same time, these two
      models of "long-term evolutionary relations" could represent "key factors" in the
      evolution between viruses and multi-cellular organisms. The capability of a
      genome to produce and emit DNA/RNA sequences or de novo created viruses which can
      be a vector of genes horizontal transmission and/or cause selective pressure on
      concurrent or predator species gives a new characteristic to viruses--the
      possibility of their acting as natural biological weapons. Finally, possibly
      evolutionary advantages of this genome capability could be one of explanations
      for the phenomena such as genome instability and its ability to emit DNA/RNA
      sequences and/or de novo created viruses, as well as evolutionary conservation of
      this unique phenomena.

PMID- 16084026
TI  - [A novel colorimetric test to study the susceptibility of human cytomegalovirus
      DNA polymerase to foscarnet].
AB  - We described a colorimetric method to determine the biochemical phenotype of wild
      type and mutated cytomegalovirus (HCMV) DNA polymerases by measuring the
      incorporation of digoxigenin-labelled nucleotides into the growing DNA chain.
      Mutations V715M and E756K, which are known to confer foscarnet-resistance, were
      used as controls. Mutation N495K and a combination of changes K415R and S291P,
      both observed in foscarnet-resistant isolates, were studied. The mutations were
      introduced by site-directed mutagenesis into wild-type gene UL54 cloned in an
      expression vector and then polymerases were synthesised by using a commercially
      available coupled transcription-translation system. The polymerase activity was
      measured with and without foscarnet. The activity of polymerases containing the
      V715M or E756K mutations was inhibited by foscarnet at concentrations 70- and 30
      fold higher than that of wild-type polymerase, respectively. Change N495K and
      combination of K415R and S291P, induced a five- and ten-fold decrease in
      susceptibility to foscarnet, respectively. The results of this non-radioactive
      assay were consistent with those obtained with the conventional radioactive
      assay. Therefore, this novel phenotypic method could be useful for the
      characterisation of mutations that confer HCMV resistance to foscarnet.

PMID- 16084027
TI  - [Neuroendocrine tumours treated with mIBG and radiolabeled peptides].
AB  - Neuroendocrine tumours are a heterogeneous group, characterized by good
      prognosis, but important disparities of the evolutionary potential. In the
      aggressive forms, the therapeutic strategies are limited. The metabolic or
      systemic radiotherapy, using radiolabelled peptides, which can act at the same
      time on the primary tumour and its metastases, constitutes a tempting therapeutic
      alternative, currently in evolution. The preliminary results are encouraging; the
      prospects are related to the development of new radiopharmaceuticals, with the
      use of other peptide analogues whose applications will overflow the framework of
      the neuroendocrine tumours.

PMID- 16084028
TI  - [A recurrent mutation of the JAK2 gene in chronic myeloproliferative disorders].

PMID- 16084030
TI  - [Selection of relevant duplicate criteria in the monitoring of Staphylococcus
      aureus methicillin resistance trends].
AB  - OBJECTIVE: Monitoring methicillin-resistant Staphylococcus aureus (MRSA) rates is
      crucial in hospital settings, but its calculation is hampered by variations
      according to duplicate isolates. The aim of this study was to assess the impact
      of applying different methods for duplicate isolate removal on the MRSA rates.
      MATERIALS AND METHODS: Trends in S. aureus resistance were analysed from isolates
      collected in a teaching hospital during a 4-year period by using a specifically
      designed software. Reference duplicate (RD) criteria were defined as one major
      and three minor differences in antibiotic patterns and a 30-day time period
      between two isolates. Variations in antibiotic patterns and time period were
      studied and compared to RD. NCCLS recommendations based upon results from the
      first isolate of a species per patient per study period, and the ONERBA
      recommendations based on phenotypic method, were also studied. RESULTS: MRSA rate
      was 31.1% when using RD. When duplicates were not eliminated, the MRSA rate
      significantly increased to 34.0% (P=0.002). When using NCCLS and ONERBA
      recommendations, the MRSA rate significantly decreased to 27.6% (P=0.002) and
      significantly increased to 33.8% (P=0.002) respectively. When no difference was
      tolerated in antibiotic pattern or when the time period was set at five days, the
      MRSA rate significantly increased to 34.3 and 34.2%, respectively (p=0.003 for
      each). CONCLUSIONS: These results suggest that criteria used to remove duplicates
      should be carefully selected to assess accurate MRSA trends.

PMID- 16084029
TI  - [VCA agar (bioMerieux) for selective isolation of vancomycin-resistant
      Enterococci (VRE) from fecal specimens].
AB  - Screening for Vancomycin Resistant Enterococci (VRE) is recommended for
      preventing nosocomial infections with VRE. The aim of this study was to assess
      the performance of VCA3 agar (bioMerieux) in VRE isolation from fecal specimens.
      220 specimens were cultured on VCA3 agar, which contains vancomycin and in
      parallel, on CAP agar (Oxoid), which is vancomycin-free. 36 vancomycin resistant
      enterococci were isolated: 24 isolates of Enterococcus faecium expressed a high
      level resistance to vancomycin and 12 isolates of E. gallinarum/casseliflavus
      exhibited resistance at low-level. The sensitivity of VCA3 appeared greater than
      that of CAP for VRE isolation: 92% (22/24) vs 79% (19/24) for E. faecium (NS,
      P>0.05) ; 83% (10/12) vs 50% (6/12) for E. gallinarum/casselliflavus (NS,
      P>0.05). As expected, initial cultures of multiple gram positive organisms were
      far more frequent on CAP agar than on VCA3 agar. The isolation rate of vancomycin
      susceptible gram positive strains was impressively lower on VCA3 medium than on
      CAP medium. VCA3 agar avoided therefore additional subcultures, useless
      identification and susceptibility tests. In conclusion, VCA3 medium could be
      useful for the direct, rapid and selective isolation of VRE from fecal specimens.

PMID- 16084031
TI  - [Epidemiological survey of a suspected nosocomial case of tuberculosis by
      spoligotyping].
AB  - Transmission of tuberculosis within hospitals has been increasingly recognized as
      a hazard for patients and health care workers. A case of pulmonary tuberculosis
      was detected in September 2003 in a nursing auxiliary working at Avicenne's
      Hospital. This 49 year-old woman was considered infected since April 2003. During
      this 6 months period, she worked in 23 distinct hospital units and could have
      contaminated patients and hospital staffs. The epidemiological survey was
      comprised for 1735 individuals (701 hospital staffs and 1034 patients). It
      encompassed clinical, para-clinical investigations and bacteriological
      investigations. Furthermore, between January 2003 and September 2004, a
      systematic comparison of 62 Mycobacterium tuberculosis strains isolated in the
      hospital was conducted by spoligotyping, a molecular typing method in order to
      access an eventual transmission. The nursing auxiliary's strain clearly showed a
      distinct spoligotype from the other investigated strains. This spoligotype was
      unique in the international spoligotype database. In this large epidemiological
      survey of a case of suspected nosocomial of tuberculosis, spoligotyping appeared
      as an interesting, easy and rapid method of molecular typing. It allowed to
      demonstrate that the nursing auxiliary tuberculosis case was unrelated to the
      others cases of tuberculosis diagnosed in the hospital during this period.

PMID- 16084033
TI  - [Prevalence and characteristics of Guillain-Barre syndromes associated with
      Campylobacter jejuni and cytomegalovirus in greater Paris].
AB  - AIM OF THE STUDY: We aimed to study prevalence and features of Campylobacter
      jejuni and cytomegalovirus (CMV)-associated Guillain-Barre syndromes (GBS) in a
      French care unit. PATIENTS AND METHODS: We studied 264 patients with GBS admitted
      at Raymond Poincare hospital (Garches) between 1996 and 2001. Clinical data were
      obtained prospectively. Sera were collected at patients entry and tested
      retrospectively for anti-C. jejuni, anti-CMV and antigangliosides GM1 et GM2
      antibodies. RESULTS: GBS associated with a serological evidence for a recent C.
      jejuni infection were the more frequent (58/264, 22%); they affected
      predominantly men of mature years (mean age: 51.3 years; sex-ratio M/F: 1.76),
      mostly after a gastrointestinal illness (52%); they were often pure motor forms
      (57%), were severe (mechanical ventilation: 40%) and associated to an anti-GM1
      IgG and/or IgM response (44%). GBS cases involving a primary CMV infection were
      less frequent (40/264, 15%), but were severe too (mechanical ventilation: 37.5%);
      they occurred preferentially in young women (mean age: 35.9 years; sex-ratio MF:
      0.82), often after respiratory tract symptoms (28%) or an influenza-like syndrome
      (15%) and were frequently associated with sensory loss (73%) and with an anti-GM2
      IgM response (47%). CONCLUSION: C. jejuni and CMV proved to be major triggering
      agents of GBS in France. They are associated with distinct presentations, which
      are both severe.

PMID- 16084034
TI  - [Enterococcal bacteremia at Nimes university hospital].
AB  - PURPOSE OF THE STUDY: The aim of this study was the description of enterococcal
      bacteremia and the evaluation of their resistance evolution to antibiotics and
      the virulence profile of these isolates. PATIENTS AND METHODS: We have studied
      all the bacteremia caused by Enterococcus spp. from the 1st of July 2003 until
      the 30th of June 2004 at Nimes university hospital. For each isolate, population,
      clinical and microbiological data were collected. Multiplex PCR allowed for the
      identification of glycoprotein resistant phenotypes and furthermore, to identify
      the main virulence genes found in the enterococci. RESULTS: Thirty-three strains
      were identified from 33 patients (60.6% male) with a median age of 68 years
      (median: 3-96). The vital prognostic was calculated in 63.6% of the cases
      (MacCabe > or =1); seven patients died during their hospitalization (21.2%). The
      infections were nosocomial in 60.6% of the cases. No epidemic was observed. The
      principal comorbidities were cardiovascular and digestive pathologies. In
      addition, 54.5% of patients had had a surgical intervention. Enterococcus
      faecalis (87.9%) was the cause of infection in the majority of cases followed by
      Enterococcus faecium. Most of the infections were monomicrobial (75.8%). E.
      faecalis was sensitive to amoxicillin and to glycopeptides but was resistant to
      norfloxacin, erythromycin and pristinamycin. The same observations were made for
      the E. faecium with the exception of amoxicillin. E. faecalis had the maximum
      number of virulence genes and E. faecium the least. CONCLUSION: The enterococcal
      bacteremia had mainly a nosocomial origin. The isolates came from digestive tract
      flora but also from catheters. The mortality rate was 21.2%. A developing
      sensitivity to erythromycin and pristinamycin was observed in comparison to the
      data of the ONERBA (2002-2003). Only one isolate was resistant to glycopeptide.
      This was the first European E. faecium containing the vanD allele. This isolate
      proved fatal to the patient. The dark evolution of enterococcal bacteremia and
      their frequent nosocomial origin induce to promote studies intended for better
      knowing the risk factors of such infections.

PMID- 16084035
TI  - The biosynthetic genes for disorazoles, potent cytotoxic compounds that disrupt
      microtubule formation.
AB  - Disorazoles are polyketides produced by the myxobacterium Sorangium cellulosum So
      ce12. Their mode of action is to inhibit tubulin polymerization and destabilize
      microtubules. Using transposon mutagenesis, two mutant strains were identified
      that produced no disorazoles. Sequencing the DNA flanking the insertions revealed
      a polyketide synthase gene cluster that would encode three polypeptides, DszA,
      DszB, and DszC, with DszC containing both nonribosomal peptide synthetase and
      polyketide synthase modules. The disorazole polyketide synthase modules lack an
      acyltransferase domain. Instead, a separate gene, dszD, encodes an AT protein,
      thus revealing that the disorazole gene cluster falls into the trans-AT Type I
      family of PKS enzymes.

PMID- 16084036
TI  - Phenotypic and genotypic properties of Streptococcus equi subsp. zooepidemicus
      isolated from harbor seals (Phoca vitulina) from the German North Sea during the
      phocine distemper outbreak in 2002.
AB  - The present study was designed to identify and compare 32 beta-hemolytic
      streptococci isolated from 28 different harbor seals of the German North Sea
      during the phocine distemper outbreak in 2002. The bacteria were identified as
      Streptococcus equi subsp. zooepidemicus based on cultural, biochemical,
      serological and molecular studies. Epidemiological investigations by PCR
      restriction fragment length polymorphism analysis of the 16S-23S rDNA intergenic
      spacer region and gene szp and by macrorestriction analysis of the chromosomal
      DNA of the strains by pulsed field gel electrophoresis revealed that all 32
      strains appeared to be identical. These results indicate that a single bacterial
      clone seemed to be distributed among the harbor seal population of the German
      North Sea during this outbreak.

PMID- 16084037
TI  - The biologic error in gestational length related to the use of the first day of
      last menstrual period as a proxy for the start of pregnancy.
AB  - OBJECTIVE: In a large unselected population of normal spontaneous pregnancies, to
      estimate the biologic variation of the interval from the first day of the last
      menstrual period to start of pregnancy, and the biologic variation of gestational
      length to delivery; and to estimate the random error of routine ultrasound
      assessment of gestational age in mid-second trimester. STUDY DESIGN: Cohort study
      of 11,238 singleton pregnancies, with spontaneous onset of labour and reliable
      last menstrual period. The day of delivery was predicted with two independent
      methods: According to the rule of Nagele and based on ultrasound examination in
      gestational weeks 17-19. For both methods, the mean difference between observed
      and predicted day of delivery was calculated. The variances of the differences
      were combined to estimate the variances of the two partitions of pregnancy.
      RESULTS: The biologic variation of the time from last menstrual period to
      pregnancy start was estimated to 7.0 days (standard deviation), and the standard
      deviation of the time to spontaneous delivery was estimated to 12.4 days. The
      estimate of the standard deviation of the random error of ultrasound assessed
      foetal age was 5.2 days. CONCLUSION: Even when the last menstrual period is
      reliable, the biologic variation of the time from last menstrual period to the
      real start of pregnancy is substantial, and must be taken into account. Reliable
      information about the first day of the last menstrual period is not equivalent
      with reliable information about the start of pregnancy.

PMID- 16084038
TI  - Variability, repeatability and phenotypic relationships of several
      characteristics of production and semen quality in rabbit.
AB  - A total of 2140 ejaculates from 156 adult males pertaining to four groups of
      bucks were analysed and the following traits were recorded: pH, ejaculate volume
      (V), mass motility (Mm), individual motility (Mi), concentration (Cn), total
      number of spermatozoa per ejaculate (TSE), percentage of sperm viability (Vi),
      percentage of sperm with acrosome integrity (NAR), percentage of sperm normalcy
      (Nr), percentage of sperm morphological abnormalities of head (H), neck-midpiece
      (Nm) and tail (T) and presence of proximal and distal cytoplasmic droplet (Dp,
      Dd). Principal component (PC) analysis and phenotypic correlations were performed
      in order to examine the relationships between qualitative and quantitative traits
      of rabbit semen. The repeatability of the traits measured was also estimated.
      Phenotypic correlations between sperm traits were estimated as the residual
      correlation from an analysis of variance, including the effects of: genetic type
      of the male, order of the ejaculate, day of collection and the permanent non
      additive random effect of the male to which the observation corresponds. The
      repeatability of these traits was analysed separately, in a set of univariate
      analyses, using VCE software. The previously defined mixed model was used for
      this analysis. The principal component analysis was performed using the Princomp
      procedure of the SAS v.8 package. The first four PC explained 62% of total
      variation: 23%, 18%, 12% and 8%, respectively. Percentage of sperm viability,
      NAR, Nr, T and Nm were the predominant variables in the first PC. Mass motility,
      Mi, pH, Cn and TSE were located in the second. Percentage of sperm with the
      presence of proximal and distal cytoplasmic droplet, NAR, Vi and Nr were the
      predominant traits in the third and V defined the fourth. Repeatability of semen
      quality traits was moderate for most of the traits. The highest values (about
      0.45) corresponded to V, Cn, Nr and Dp and the lowest (about 0.10) to H and Nm.
      Repeatability of the first ejaculate was greater than that of the second for pH,
      Mm, Mi, H, Dp and Dd.

PMID- 16084039
TI  - The post-thaw quality of ram sperm held for 0 to 48 h at 5 degrees C prior to
      cryopreservation.
AB  - The effects of holding diluted ram semen at 5 degrees C for up to 48 h prior to
      cryopreservation were investigated. Semen from six rams was collected by electro
      ejaculation in the autumn and again from six different rams in the spring. The
      sperm concentration and motility were determined using spectrophotometry and
      computerized automated semen analysis, respectively. Samples were diluted at 23
      degrees C to 400 x 10(6)cells/ml in a one-step Tris-egg yolk-glycerol (5%, v/v)
      media, cooled to 5 degrees C over 2h and maintained at 5 degrees C for the
      duration of the experiments. Aliquots were loaded into 0.5 ml French straws at 0,
      24 or 48 h after cooling, frozen in liquid nitrogen vapor for 12-13 min, 4.5 cm
      above the liquid nitrogen, and plunged into liquid nitrogen for storage. After
      thawing, autumn samples frozen after 0, 24, or 48 h of storage exhibited similar
      percentages of motility (29, 31, 36%, respectively), progressively motility (16,
      15, 17%, respectively), plasma membrane integrity (28, 35, 29%, respectively) and
      live acrosome-reacted cells (0.4, 0.6, 0.8%, respectively; P>0.05). In addition,
      the quantity of sperm that bound to hen's egg perivitelline membranes after being
      held at 5 degrees C for 0, 24, or 48 h was not significantly different when the
      values were expressed as means of the quantity of sperm (155, 177, 106 sperm,
      respectively) or as the proportion of sperm inseminated (0.39, 0.49, 0.34,
      respectively; P>0.05). Likewise, ram sperm collected in the spring and frozen at
      0, 24 and 48 h after cooling had similar (P>0.05) total motility (21, 25, 20%,
      respectively), progressive motility (14, 15, 11%, respectively), plasma membrane
      integrity (26, 33, 31%, respectively) and live acrosome-reacted cells (3.7, 3.5,
      3.2%, respectively; P>0.05). The 0 h holding time had significantly less sperm
      bound to a hen's egg perivitelline membrane compared to the 48 h holding time
      (250 and 470 sperm, respectively) although the 24h holding time was not different
      from the 0 or 48 h holding time (281 sperm; P<0.05) but analysis of the
      proportion of the total sperm inseminated resulted in no significant differences
      observed (P>0.05). These results indicate that ram sperm can be held at 5 degrees
      C for up to 48 h prior to freezing with no injurious effects on motility,
      membrane integrity, or fertilizing potential as indicated by membrane binding
      ability.

PMID- 16084040
TI  - Integration of future biotechnologies into the equine industry.
AB  - There has and will continue to be reproductive techniques available that have a
      positive impact upon the equine breeding industry. This review focuses on semen
      technologies that have been developed or are in the process of being developed.
      The use of fluorescent dyes and flow cytometry has provided the researcher and
      clinician with powerful tools to evaluate several sperm attributes. These
      procedures have been utilized to evaluate sperm viability, acrosome status,
      mitochondrial status, DNA integrity and stages of capacitation. Flow cytometry
      allows several sperm attributes to be evaluated on thousands of spermatozoa in a
      matter of seconds. Development of procedures for insemination of mares with
      relatively small numbers of spermatozoa has the potential to change how stallions
      and their semen are managed. This review discusses the use of insemination of
      fresh, frozen and sex-sorted spermatozoa in relatively small numbers compared
      with conventional insemination technologies. The recent acceptance of frozen
      thawed semen by many of the major breed registries has stimulated an increase in
      research on frozen semen. Many of the studies have focused on identifying damage
      during the freezing and thawing process. Numerous studies also have been
      conducted to modify freezing extenders so that the sperm are protected during the
      freezing and thawing process. The production of in vitro-produced embryos is
      extremely limited in the horse due to the failure of in vitro fertilization.
      However, intracytoplasmic sperm injection (ICSI) has been used for the production
      of foals from stallions that have less than typical sperm numbers or from
      stallions that have died and a limited quantity of frozen semen is available.
      This technique has been used by several laboratories to produce embryos in vitro.
      The breeder and veterinarian now have access to techniques that allow assessment
      of semen quality, improvement of procedures for freezing and thawing and
      insemination of mares with fewer numbers of spermatozoa. It is likely that the
      next decade will also produce tremendous advances in semen technologies that can
      be utilized in the horse industry.

PMID- 16084041
TI  - Challenges facing sex preselection of stallion spermatozoa.
AB  - Since the production of the first live offspring from sex-sorted spermatozoa in
      1989, there have been many developments in the fluorescence-activated cell
      separation (FACS) procedures to preselect X- and Y-chromosome bearing spermatozoa
      prior to insemination. During this time, FACS technology has been applied to a
      range of species and has resulted in offspring from rabbits, cattle, sheep, elk
      and horses. In horses, satisfactory fertility rates have been achieved after
      hysteroscopic insemination of 20 x 10(6) fresh or stored, sex-sorted spermatozoa.
      However, many of the sperm processing protocols are still based on the original
      protocol and components of these procedures may not necessarily be suitable for
      the stallion. This review examines the details of FACS protocols that have
      resulted in the production of live offspring and makes comparisons with the
      published stallion protocols in an attempt to determine how best to improve the
      fertility of sorted, frozen-thawed stallion spermatozoa.

PMID- 16084042
TI  - Spermatozoal response to osmotic stress.
AB  - The process of sperm cryopreservation imparts on sperm cells the stress of low
      temperature and drastic osmotic change. Damage to the cell plasma membrane
      results in cell injury in a number of cellular structures and associated
      functions. Studies in the author's laboratory have focused upon the various
      mechanisms of osmotic and thermal injury including plasma membrane lipid
      structure, mitochondrial membrane potential, and intracellular signaling. We have
      determined that cryoinjury to sperm, as for somatic cells, is a multi-factorial
      event and some of these events are reversible while some are not.

PMID- 16084043
TI  - Release characteristics of anionic drug compounds from liquid crystalline gels I:
      Passive release across non-rate-limiting membranes.
AB  - Liquid crystalline gels (LCG) offer the formulator dynamic and flexible vehicles,
      into which actives, enhancers and other adjuvants with a wide range of
      physicochemical properties can be incorporated. This is achievable because of the
      biphasic oil/water composition of the gel. In this paper, the suitability of an
      isotropic liquid crystalline gel is investigated for a range of anionic drug
      molecules, with particular emphasis on sodium diclofenac. Parameters, which have
      been investigated, include the mode of vehicle preparation, the effect of the
      concentration of the drug and how buffering the gel and/or the receptor medium
      affect the release profiles. Such profiles have been measured for the sodium
      salts of benzoate, salicylate and indomethacin. The passive release from the
      standard system was found to adhere to matrix-controlled diffusion. An increase
      in concentration leads to a non-linear increase in the cumulative release of
      sodium diclofenac from the gels. In direct contrast to the result reported for
      cationic salbutamol base, optimum release from the gel was achieved when neither
      the receptor medium nor the aqueous phase of the gel was buffered. The
      percentages released of the sodium salts of benzoate, salicylate and
      indomethacin, after 24 h, were determined to be 25, 26 and 19%, respectively, and
      these are significantly greater than the release of sodium diclofenac. This
      suggests that diclofenac undergoes ion-pairing or complexation within the gel,
      which inhibits its diffusion from the vehicle. Future papers will report on the
      incorporation of enhancers and the effects of iontophoresis on the release
      profiles of drugs from these gels, and ultimately on the transdermal transport of
      drugs from these vehicles across human and porcine skin.

PMID- 16084044
TI  - The effect of bee propolis on oral pathogens and human gingival fibroblasts.
AB  - Propolis is one of the few natural remedies that have maintained its popularity
      over a long period of time. The aim of this study is to investigate the
      antimicrobial properties of six propolis solutions and evaluate their
      cytotoxicity on gingival fibroblasts at different dilutions. Two different
      solutions of powder propolis (Sigma) and Turkish propolis were prepared and
      propylene glycol (PG) and alcohol were used as solvents for each propolis sample.
      In addition to the four propolis solutions, two other propolis samples of far
      geographic regions (USA and Australia) were included in the study. The
      antibacterial effects of six solutions on oral pathogen microorganisms were
      tested and their cytotoxic effects on human gingival fibroblasts were evaluated
      by MTT assay. The effective dilutions of the six propolis samples on
      periodontopathogen microorganisms were found to be cytotoxic to gingival
      fibroblasts. All solutions had strong antifungal activity and the effective
      dilutions were safe for gingival fibroblasts. Propolis could have a promising
      role in the future medicine, if appropriate solutions can be prepared being
      strongly antibacterial and non-cytotoxic as well.

PMID- 16084045
TI  - Antiophidian properties of the aqueous extract of Mikania glomerata.
AB  - Aqueous extracts, prepared from dried or fresh roots, stems or leaves of Mikania
      glomerata, a plant found in Mata Atlantica in Southeastern Brazil, were able to
      efficiently neutralize different toxic, pharmacological, and enzymatic effects
      induced by venoms from Bothrops and Crotalus snakes. Phospholipase A(2) activity
      and the edema induced by Crotalus durissus terrificus venom were inhibited around
      100 and approximately 40%, respectively, although this inhibition was only
      partial for Bothrops venoms. The hemorrhagic activity of Bothrops venoms
      (Bothrops altenatus, Bothrops moojeni, Bothrops neuwiedi, and Bothrops
      jararacussu) was significantly inhibited by this vegetal species, while the
      clotting activity of Crotalus durissus terrificus, Bothrops jararacussu, and
      Bothrops neuwiedi venoms was totally inhibited. Although, the mechanism of action
      of Mikania glomerata extract is still unknown, the finding that no visible change
      was detected in the electrophoretic pattern of snake venom after incubation with
      the extract excludes proteolytic degradation as a potential mechanism. Since the
      extract of Mikania glomerata significantly inhibited the studied snake venoms, it
      may be used as an alternative treatment to serumtherapy and, in addition, as a
      rich source of potential inhibitors of PLA(2)s, metalloproteases and
      serineproteases, enzymes involved in several physiopathological human and animal
      diseases.

PMID- 16084046
TI  - Bronchodilator activity of Phymatodes scolopendria (Burm.) Ching and its
      bioactive constituent.
AB  - Phymatodes scolopendria (Burm.) Ching (Polypodiaceae) is widely used in the
      Eastern coast of Madagascar to treat respiratory disorders. Bioassay-guided
      fractionation using guinea pig trachea pre-contracted with histamine to monitor
      the activity led to the isolation of 1,2-benzopyrone (coumarin) as the main
      active constituent. Effectively, it induced a concentration-dependent relaxation
      of the histamine with a median effective concentration (EC(50)) of 35.03
      microg/ml, or carbachol (EC(50) = 33.41 microg/ml) pre-contracted guinea pig
      trachea, and also provoked 100% relaxation at 72.10 microg/ml. It was less active
      either on KCl pre-contracted trachea (EC(50) = 130.78 microg/ml) or endothelium
      denuded trachea (153.4 +/- 22 microg/ml). It inhibited, in a non-competitive
      manner, the histamine and the external calcium spasm effect on the isolated
      trachea but it did not significantly modify the broncho-constrictive activity of
      KCl. When combined with theophylline, coumarin produced a significant additive
      relaxing effect on pre-contracted trachea. Furthermore, its bronchodilator effect
      was not blocked by propranolol. In vivo, pre-treated guinea pig with coumarin
      showed significant resistance to histamine inhalation, with an adequate dose
      protecting 50% of the tested animals (AD(50)) of 75 mg/kg. These results indicate
      that the bronchodilator effect of coumarin is partly due to the endothelium
      dependent tracheal relaxation, and may be mediated through a non-specific
      tracheal relaxation.

PMID- 16084047
TI  - Method for determining the average degree of substitution of o-vanillin
      derivatized porcine somatotropin.
AB  - Electrospray mass spectral observation directly on a sample of a derivatized
      protein, such as porcine somatotropin (pST), affords a method for evaluating the
      degree of substitution of this protein. Derivatization of the lysine residues and
      the terminal amino residue here by formation of a Schiff base with a small
      aromatic aldehyde (in this case, o-vanillin) affords stabilization of the protein
      so that it may be used in a controlled release veterinary pharmaceutical
      formulation. This method permits direct observation of substitutions,
      optimization of manufacturing procedures for producing a commercial product, and
      permits quality evaluation of material.

PMID- 16084048
TI  - Monitoring the neuropeptide metabolites by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - The developments of bio-analytical methods for analyzing bioactive peptides are
      of paramount importance. Neuropeptides and their bioactive fragments play a vital
      role in the regulation of many biological processes and diseases. This paper
      presents the use of matrix-assisted laser desorption/ionization (MALDI) time-of
      flight (TOF) mass spectrometry (MS) method for monitoring neuropeptides along
      with their degradation products in plasma samples from cancer patients. The
      neuropeptides focused in this study were beta-endrophin, substance P, and
      bradykinin. The method involves the enzyme digestion of the neuroactive peptides
      followed by MALDI-MS sample preparation and subsequent acquisition of the MS
      spectral data. The mass spectral profile identifies most of the C-terminal and N
      terminal peptides, and the mass accuracy was in the range of -1.68 to 1.46 Da
      with the mass spectrometer utilised. Analysis of the neuropeptide degradation
      patterns from the cancer patients were compared with the controls showed similar
      results. The study reveals that this approach can be used to identify the
      enzymatic digestion products of protein.

PMID- 16084049
TI  - Comparative evaluation between capillary electrophoresis and high-performance
      liquid chromatography for the analysis of florfenicol in plasma.
AB  - A capillary electrophoresis (CE) and a reversed phase high-performance liquid
      chromatography (RP-HPLC) method with UV detection have been developed for
      florfenicol analysis in plasma samples. The suitabilities of both methods for
      quantitative determination of florfenicol were approved through validation
      specification, such as linearity, precision, selectivity, accuracy, limit of
      detection and quantification. The capillary electrophoresis (CE) and high
      performance liquid chromatography (HPLC) assay were compared by analyzing a
      series of plasma samples containing florfenicol in different concentrations using
      the two methods. The extraction procedure is simple and no gradient elution or
      derivatization is required. Furthermore, the analysis time of the CE method is
      two times shorter than the respective parameter in HPLC and solvent consumptions
      is considerably lower. The calibration curve were linear to at least 0.05-10
      microg/ml (r = 0.9998) and 0.1-10 microg/ml (r = 0.9998) for CE and HPLC,
      respectively. The separation efficiency are good for both methods. The detection
      limits for florfenicol were 0.015 microg/ml with CE and 0.03 microg/ml with HPLC
      and CE method gave lower value, even though UV detector was applied in the both
      cases. The both methods were selective, robust and reliable quantification of
      florfenicol and can be useful for clinical and biomedical investigations.

PMID- 16084050
TI  - An investigation to examine the inter-tester and intra-tester reliability of the
      Rolimeter knee tester, and its sensitivity in identifying knee joint laxity.
AB  - PURPOSE: The purpose of this study is to evaluate the Rolimeter knee tester
      (Aircast, Europe) as reliable and clinically sensitive tool for identifying and
      quantifying knee joint laxity utilising a sample of both known ACLD and normal
      knees. METHODS: Thirty matched subjects (15 known ACLD and 15 normal subjects)
      were tested for knee joint laxity using the Rolimeter. Each subject was measured
      at both 90 degrees and 30 degrees of knee flexion, by each of the six
      investigators. This was then repeated again by all six investigators so that
      inter-tester and intra-tester reliability could be examined. RESULTS: Results
      showed that there was good reliability between testers, and intra-tester
      reliability was good for both left and right knees in both 90 degrees and 30
      degrees of flexion. Results also demonstrated a high level of sensitivity for
      determining knee joint laxity in ACLD compared to normal knees. CONCLUSION: The
      Rolimeter knee tester is a reliable device for quantifying knee joint laxity, and
      is sensitive enough to identify anterior cruciate ligament deficiency.

PMID- 16084051
TI  - Conventional surgery and systemic chemotherapy for peritoneal carcinomatosis of
      colorectal origin: a prospective study.
AB  - AIMS: To report the results of standard therapy for peritoneal carcinomatosis of
      colorectal origin, which consists of conventional surgery and systemic
      chemotherapy. METHOD: In a prospective study 50 patients with proven peritoneal
      carcinomatosis of colorectal origin were treated with conventional surgery
      combined with 5-fluorouracil and leucovorin, or irinotecan in patients treated by
      5-fluorouracil within 12 months prior to entry. Survival and progression-free
      survival were studied and prognostic factors were analysed. RESULTS: The median
      survival time was 12.6 months. The median time to progression was 7.6 months.
      Location of primary tumour and result of conventional surgery and systemic
      chemotherapy were prognostic factors related to survival. CONCLUSION: The
      survival time of patients with peritoneal carcinomatosis of colorectal origin
      seems to be increased in patients treated by conventional surgery and systemic
      chemotherapy when compared to minimal treatment.

PMID- 16084052
TI  - The significance of melanoma micrometastases in the sentinel lymph node.

PMID- 16084053
TI  - Balloon catheter hypoxic pelvic perfusion with mitomycin C and melphalan for
      locally advanced tumours in the pelvic region: a phase I-II trial.
AB  - AIMS: To investigate the feasibility of hypoxic pelvic perfusion (HPP), using
      balloon catheter techniques as treatment modality for locally advanced pelvic
      malignancies. METHODS: In a phase I--II study, 16 patients with various non
      resectable pelvic tumours were treated with two HPP with MMC and melphalan,
      followed by radiotherapy (25 Gy) and surgical resection if feasible. Toxicity and
      procedure related complications were documented. Tumour responses were assessed
      by MRI or CT. Pain reductive effects were assessed by evaluation of pain
      registration forms. RESULTS: HPP resulted in augmented regional drug
      concentrations with relatively low systemic levels. Some severe systemic toxicity
      was observed. One procedure related death occurred. Pain reduction effects were
      short-lived. Ten patients had radiological NC, two PD and one PR. In 11 patients
      surgical resection was performed, which was microscopically radical in six cases.
      Mean survival was 26.8 months (range 1--86). CONCLUSION: The seemingly favorable
      pharmacokinetic profiles observed with HPP in this and other studies can still
      lead to severe systemic toxicity. In terms of survival, local (re-)recurrence and
      pain reduction there seems no benefit of addition of HPP to pre-operative
      radiotherapy. HPP with MMC and melphalan, does not seem a therapeutic option in
      patients with locally advanced pelvic tumours.

PMID- 16084054
TI  - Validation of a diffusion chamber as in vitro system for the analysis of compound
      diffusibility through cartilage tissue.
AB  - The validation of a diffusion chamber comprising a donor and a receptor side
      separated by a cartilage membrane was undertaken according to the basic
      principles described by Peng et al. (1998). The study had three targets: first to
      evaluate the chamber as in vitro system by the examination of the diffusibility
      of compound through bovine cartilage samples; second the analysis of the affinity
      of compound (RS-130830) to cartilage; third to test the influence of two pre
      incubation periods (one or three nights) of the cartilage samples. The validation
      of the chamber as in vitro system for the analysis of compound diffusibility and
      affinity to cartilage was performed using membrane slices of fresh bovine
      cartilage and a hydroxamic acid derivative (RS-130830) known as matrix
      metalloproteinase inhibitor (MMPI). The influence of the pre-incubation of
      cartilage was also examined. Compound concentrations in donor, receptor and
      membrane were determined by high performance liquid chromatography-mass
      spectrometry (HPLC-MS). Diffusion could be demonstrated after 6 h and finally 24
      h incubation: the compound concentration in the receptor increased from 0 to 35
      microM (mean) while it decreased in the donor from 200 to 144 microM (mean). We
      also found compound in the cartilage membrane (approximately 1.2 nmol (mean)).
      Pre-incubation of cartilage samples in culture buffer is suitable as a storage
      procedure, since the results on the donor side only were influenced significantly
      but not for the receptor and the cartilage affinity. Thus, the system could
      clearly reflect relevant properties of the tested compound with regard to its
      diffusibility and affinity to cartilage tissue.

PMID- 16084055
TI  - Effects of pulsed electromagnetic fields on articular hyaline cartilage: review
      of experimental and clinical studies.
AB  - Osteoarthritis (OA) is the most common disorder of the musculoskeletal system and
      is a consequence of mechanical and biological events that destabilize tissue
      homeostasis in articular joints. Controlling chondrocyte death and apoptosis,
      function, response to anabolic and catabolic stimuli, matrix synthesis or
      degradation and inflammation is the most important target of potential
      chondroprotective treatment, aimed to retard or stabilize the progression of OA.
      Although many drugs or substances have been recently introduced for the treatment
      of OA, the majority of them relieve pain and increase function, but do not modify
      the complex pathological processes that occur in these tissues. Pulsed
      electromagnetic fields (PEMFs) have a number of well-documented physiological
      effects on cells and tissues including the upregulation of gene expression of
      members of the transforming growth factor beta super family, the increase in
      glycosaminoglycan levels, and an anti-inflammatory action. Therefore, there is a
      strong rationale supporting the in vivo use of biophysical stimulation with PEMFs
      for the treatment of OA. In the present paper some recent experimental in vitro
      and in vivo data on the effect of PEMFs on articular cartilage were reviewed.
      These data strongly support the clinical use of PEMFs in OA patients.

PMID- 16084056
TI  - Secondary hyperparathyroidism is associated with vitamin D receptor polymorphism
      and bone density after renal transplantation.
AB  - Immunosuppresive treatment and secondary hyperparathyroidism (SHPT) are
      considered among the most important pathogenetic factors for post-renal
      transplant bone disease. The aim of this study was to investigate the
      relationships among vitamin D receptor (VDR) gene polymorphism, parathyroid
      hormone (PTH) levels and bone density in renal transplant recipients. We enrolled
      75 patients (50 male and 25 female, mean age 47+/-11 years) who had undergone
      kidney transplantation 53+/-4 months before. All patients underwent an evaluation
      of the main biochemical parameters of bone metabolism as well bone densitometry.
      VDR alleles were typed by a PCR assay based on a polymorphic BsmI restriction
      site. When patients were categorized according to the VDR genotype (BB, Bb, bb),
      serum creatinine and the cumulative doses of immunosuppressive drugs were similar
      across the groups. PTH levels higher than 80 pg/ml were found in 53.6% of the
      patients, with the highest values being detected in the bb VDR genotype (P<0.05).
      PTH was significantly correlated to urinary NTx values. Bone density was low in
      the whole population; however, spinal bone density was lower in the bb subgroup
      (P<0.02). In the whole population, only PTH (P<0.05) and body mass index (P<0.01)
      were independent predictors of spinal bone density. Grouping patients by the VDR
      gene polymorphism, only PTH continued to be an independent predictor of spinal
      bone density in the bb allele subgroup (R(2) Adj.=0.17). We can conclude that the
      VDR genotype polymorphism affects bone density of renal transplant recipients via
      its effects on the severity of SHPT.

PMID- 16084057
TI  - Cell transplantation therapy in re-animating severely head-injured patients.
AB  - The results of controlled, retrospective clinical investigation of applying cell
      transplantation (CT) therapy in 38 severely head-injured patients are presented.
      The patients initially were in state of coma (Glasgow coma scale score 3--7),
      owing to their traumatic brain injuries. Cells prepared from fetal nervous and
      hematopoietic tissues were grafted subarachnoidally via lumbar puncture. The
      control group consisted of 38 patients and was clinically comparable with the
      trial one. From the results obtained it appears that CT treatment promoted both
      wakening consciousness of the patients and their following neurological
      rehabilitation. A death-rate in the trial and control group was 5% (two cases)
      and 45% (17 cases), respectively. According to a Glasgow scale, favorable
      (good+satisfactory) outcomes of a disease were noted in 33 (87%) cell-grafted and
      only in 15 (39%) control patients. Statistical analysis revealed that CT
      treatment generally improved the outcomes by 2.5-fold. No serious complications
      of CT therapy were noted. The results point out a possible rationality of
      applying CT therapy in severely head-injured patients as early as within acute
      period of a disease.

PMID- 16084058
TI  - Type of exercise and vascular remodelling.

PMID- 16084059
TI  - Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and Secreted Protein
      Acidic and Rich in Cysteine (SPARC) on human cultured glioblastoma cells.
AB  - INTRODUCTION: Glioblastoma is a highly malignant brain tumor with a high-invasive
      phenotype, so the prognosis is unfavorable, even in response to multidisciplinary
      treatment strategies. Obviously, therefore, a better therapeutic strategy is
      needed. Resveratrol has been reported to be one of the most potent
      chemopreventive agents inhibiting the cellular processes associated with tumor
      development, including initiation, promotion, and progression. MATERIALS AND
      METHODS: In this study we used RT-PCR, western blot and SDS-zymography to
      investigate the effect of resveratrol on the expression of genes and proteins
      involved in the extracellular matrix remodeling associated with tumor invasion in
      human cultured glioblastoma cells treated for 24, 48 and 72 h. We analyzed the
      expression of matrix metalloproteinase-2 (MMP-2), the main mediator of
      glioblastoma invasiveness, and the Secreted Protein Acidic and Rich in Cysteine
      (SPARC), involved in the regulation of cell-matrix interactions. RESULTS: Our
      results show a dose-related decrease of MMP-2 mRNA and protein levels 72 h after
      resveratrol treatment, and lower SPARC gene and protein expression 72 h after
      resveratrol treatment. This indicates that resveratrol may influence the two
      major factors in the ECM remodeling occurring with tumor invasion, suggesting it
      may have uses as a therapeutic agent for brain tumors.

PMID- 16084060
TI  - Chronic treatment with flumazenil enhances binding sites for convulsants at
      recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptors.
AB  - GABA(A) receptors mediate most of the fast inhibitory neurotransmission in the
      brain. Prolonged occupancy of these receptors by ligands leads to regulatory
      changes often resulting in reduction of receptor function. The mechanism of these
      changes is still unknown. In this study, stably transfected human embryonic
      kidney (HEK) 293 cells were used as a model to study the effects of prolonged
      flumazenil (antagonist of benzodiazepine binding sites at GABA(A) receptors)
      exposure on the recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptors, the most
      common type of GABA(A) receptors found in the brain. Exposure (48 h) of HEK 293
      cells stably expressing recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptors to
      flumazenil (1 or 5 microM) in the presence of GABA (1 microM), enhanced the
      maximum number (B(max)) without affecting the affinity (K(d)) of [(3)H]TBOB
      labeled binding sites for convulsants. Diazepam (1 nM-1 mM) in the presence of
      GABA (1 microM) modulated [(3)H]TBOB binding to control and flumazenil pretreated
      cells according to a two-site model. No significant differences between the
      groups were observed in either the potency or efficacy of diazepam to modulate
      [(3)H]TBOB binding, as evidenced by a lack of significant changes between their
      IC(50) and I(max) values. The results suggest that chronic exposure of HEK 293
      cells stably expressing recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptors to
      flumazenil up-regulates the binding sites for convulsants, but it does not appear
      to affect the functional coupling between these sites and benzodiazepine binding
      sites. Along with our recent data, these results suggest that chronic treatment
      with flumazenil enhances the number of GABA(A) receptors.

PMID- 16084061
TI  - Nested genes in the human genome.
AB  - Here we studied one special type of gene, i.e., the nested gene, in the human
      genome. We collected 373 reliably annotated nested genes. Two-thirds of them were
      on the strand opposite that of their host gene. About 58% coding nested gene
      pairs were conserved in mouse and some were even maintained in chicken and fish,
      while nested pseudogenes were poorly conserved. Ka/Ks analysis revealed that
      nested genes were under strong selection, although they did not demonstrate
      greater conservation than other genes. With microarray data we observed that two
      partners of one nested pair seemed to be expressed reciprocally. A significant
      proportion of nested genes were tissue-specifically expressed. Gene ontology
      analysis demonstrated that quite a number of nested genes participated in
      cellular signal transduction. Based on these observations, we think that nested
      genes are a group of genes with important physiological functions.

PMID- 16084062
TI  - Analysis of genetic variability within Thelazia callipaeda (Nematoda:
      Thelazioidea) from Europe and Asia by sequencing and mutation scanning of the
      mitochondrial cytochrome c oxidase subunit 1 gene.
AB  - This study investigated genetic variability within the 'eyeworm'Thelazia
      callipaeda (Nematoda: Thelazioidea) from Europe and Asia by polymerase chain
      reaction (PCR)-coupled sequencing and mutation scanning of the mitochondrial
      cytochrome c oxidase subunit 1 gene (cox 1). Eight different sequence variants of
      cox 1 (haplotypes) were determined for the 50 individual adult specimens of T.
      callipaeda (from dogs, foxes or cats from Italy, Germany and the Netherlands and
      from dogs from China and Korea). Nucleotide variation (0.3--2%) was detected at
      23 of 649 positions in the cox 1. Six of these positions were invariable among
      all 37 individuals from Europe and among the 13 individuals from Asia
      (irrespective of host origin) but differed (five G<-->A and one C<-->T changes)
      between Europe and Asia. PCR-based single-strand conformation polymorphism (SSCP)
      analysis of the most variable portion (v-cox 1) of the cox 1 was validated (for a
      subset of samples) as a tool to rapidly screen for genetic (haplotypic)
      variability. The results for the SSCP analysis and sequencing were concordant,
      indicating that the mutation scanning approach provides a useful tool for
      investigating the population genetics and molecular ecology of T. callipaeda.

PMID- 16084063
TI  - Wnt/beta-catenin signaling inhibits death receptor-mediated apoptosis and
      promotes invasive growth of HNSCC.
AB  - The Wnt/beta-catenin signaling pathway plays a critical role in cell
      proliferation and oncogenesis. It has been found to be chronically activated in a
      variety of human cancers, including head and neck squamous cell carcinoma
      (HNSCC). Previously, we have found that the activation of the Wnt/beta-catenin
      signaling pathway inhibits mitochondria-mediated apoptosis. In this study, we
      extended our studies to determine whether the Wnt/beta-catenin signaling pathway
      inhibited death receptor-mediated apoptosis in HNSCC cells. We found that
      Wnt/beta-catenin inhibited not only tumor necrosis factor (TNF)/c-Myc-mediated
      apoptosis, but also cell detachment-mediated apoptosis (anoikis) which is
      dependent on the death receptor signaling pathway. Interestingly, we also
      observed that the Wnt/beta-catenin signaling pathway induced HNSCC cell
      scattering and promoted cell invasion in the Matrigel, both of which are
      hallmarks for the invasive growth of HNSCC. Consistently, the over-expression of
      beta-catenin promoted HNSCC tumor growth in nude mice. Taken together, our
      results suggest that the Wnt/beta-catenin signaling pathway plays dual functions
      in HNSCC development: promoting both cell survival and invasive growth of HNSCC
      cells.

PMID- 16084064
TI  - Novel function of POSH, a JNK scaffold, as an E3 ubiquitin ligase for the Hrs
      stability on early endosomes.
AB  - POSH (plenty of SH3s) acts as a scaffold that links activated Rac1 and downstream
      c-Jun N-terminal kinase (JNK) signaling modules. However, it is unknown whether
      it's functional domain-mediated roles including the interesting RING-finger
      domain or its cellular function. Here, we provide evidence that subcellular
      localization of POSH is regulated by a particular domain of the protein and POSH
      was colocalized with hepatocyte growth factor-regulated tyrosine kinase substrate
      (Hrs) on early endosomes via interaction of Hrs with POSH's two rear SH3 domains.
      Moreover, the RING domain of POSH specifically regulates the stability of Hrs,
      but not of JNK1, via a ubiquitin-proteasomal degradation pathway. Finally, we
      demonstrate that JNK1 does not interact with Hrs under the conditions of POSH
      interacted with Hrs, but instead reduces the POSH-catalyzed ubiquitination of Hrs
      and their reciprocal interaction. Together, these data suggest that POSH has a
      distinct role as a specific E3 ubiquitin ligase for Hrs on early endosomes, and
      there exists a relationship between its separate activities as a scaffold and as
      an E3.

PMID- 16084065
TI  - Signal transduction gRABs attention.
AB  - Rab proteins are small GTPases involved in the regulation of vesicular membrane
      traffic. Research done in the past years has demonstrated that some of these
      proteins are under the control of signal transduction pathways. Still, several
      recent papers point out to a new unexpected role for this family of Ras-related
      proteins, as potential regulators of intracellular signaling pathways. In
      particular, several evidence indicate that members of the Rab family of small
      GTPases, through their effectors, are key molecules participating to the
      regulation of numerous signal transduction pathways profoundly influencing cell
      proliferation, cell nutrition, innate immune response, fragmentation of
      compartments during mitosis and apoptosis. Even more surprisingly, direct
      involvement of Rab proteins in signaling to the nucleus has been demonstrated.
      This review will focus on aspects of Rab proteins function connected to signal
      transduction and, in particular, connections between membrane traffic and other
      cell pathways will be examined.

PMID- 16084066
TI  - Preventive action of green tea from changes in the liver antioxidant abilities of
      different aged rats intoxicated with ethanol.
AB  - OBJECTIVE: The present study investigated the influence of green tea as a source
      of water-soluble antioxidants on the liver antioxidant potential of different
      aged rats chronically intoxicated with ethanol. METHODS: Rats (2, 12, and 24 mo
      old) were fed for 5 wk on a control or an ethanol Lieber-DeCarli diet with and
      without green tea (7 g/L). The activity and level of enzymatic and non-enzymatic
      antioxidants and the level of markers of protein and lipid oxidation in the liver
      of rats were examined. RESULTS: The activities of superoxide dismutase and
      catalase and levels of vitamins C, E, A, and beta-carotene were significantly
      decreased, whereas activities of glutathione peroxidase and glutathione reductase
      and the level of reduced glutathione significantly increased during aging. The
      ethanol diet caused a significant decrease in activity of antioxidant enzymes and
      in the level of non-enzymatic antioxidants tested. Administration of green tea to
      ethanol-treated rats of different ages partly normalized the activity of enzymes
      and the level of non-enzymatic antioxidants. Changes in antioxidant ability
      observed during aging were accompanied by increased levels of markers of lipid
      and protein modifications that also were intensified by ethanol. Green tea caused
      a decrease in lipid and protein oxidation in aged and ethanol-treated rats. The
      protective effect of green tea was confirmed by the significantly lower activity
      of biomarkers of liver damage (alanine and aspartate aminotransferases) in the
      serum of rats that received green tea with ethanol compared with rats from the
      control ethanol group. CONCLUSIONS: The use of green tea appears to be beneficial
      to rat liver by decreasing oxidative stress caused by ethanol and/or aging.

PMID- 16084067
TI  - Present-day mercury resistance transposons are common in bacteria preserved in
      permafrost grounds since the Upper Pleistocene.
AB  - Transposons closely related to mercury resistance transposons Tn5041, Tn5053, and
      Tn5056, which have been previously described in present-day bacteria, were
      detected in a survey of 12 mercury-resistant Pseudomonas strains isolated from
      permafrost samples aged 15-40 thousand years. In addition, Tn5042, a novel type
      of mercury resistance transposon, was revealed in the permafrost strain
      collection and its variants found to be common among present-day bacteria. The
      results reveal that no drastic changes in the distribution mode of the different
      types of mercury resistance transposons among environmental bacteria have taken
      place in the last 15-40 thousand years.

PMID- 16084068
TI  - Effectiveness of clozapine, olanzapine, quetiapine, risperidone, and haloperidol
      monotherapy in reducing hostile and aggressive behavior in outpatients treated
      for schizophrenia: a prospective naturalistic study (IC-SOHO).
AB  - OBJECTIVE: Antipsychotic medications may reduce hostile and aggressive behavior
      in schizophrenia. This study compared the effectiveness of antipsychotics in the
      treatment of aggression. METHOD: The Intercontinental Schizophrenia Outpatient
      Health Outcomes (IC-SOHO) study compares the effectiveness of antipsychotic
      treatments in practice setting. Schizophrenia outpatients who initiated or
      changed to a new antipsychotic are followed in this non-interventional,
      prospective observational study for up to 3 years, with 6-months data now
      available on the entire cohort (N=7655). The presence or absence of verbal or
      physical hostility/aggression was assessed retrospectively for the period of 6
      months before enrollment, and prospectively in the period of 6 months after
      enrollment (the study treatment period). At baseline, patients in five
      monotherapy treatment groups (combined N=3135) were prescribed one of the
      treatments: clozapine, olanzapine, quetiapine, risperidone, or haloperidol, and
      had complete data. RESULTS: Hostile/aggressive behavior was reduced during the
      treatment period. Olanzapine and risperidone were significantly superior to
      haloperidol and to clozapine in this respect. These results remained essentially
      unchanged when adjusting for baseline imbalances in age, gender, age of onset,
      and substance abuse. CONCLUSIONS: As monotherapy, both olanzapine and risperidone
      were superior to haloperidol and clozapine in reducing aggression. The relative
      lack of effectiveness of clozapine may be specific to this study population.

PMID- 16084069
TI  - Low-dose estradiol alters brain activity.
AB  - Although several studies have examined the effects of estrogen replacement
      therapy (ERT) on neural activity associated with tasks of learning and memory, no
      study has examined such effects on a sustained attention task. This study
      examined the effect of low-dose estrogen replacement therapy on hemodynamic
      activity elicited by a visual three-stimulus oddball task recorded using event
      related functional magnetic resonance imaging (fMRI). Participants included 16
      women between the ages of 73 and 84 who were part of a randomized controlled
      double-blind study to evaluate the effect of an ultralow dose micronized
      estradiol on bone. No significant differences in behavioral performance were
      found with ERT. However, there was evidence that ERT group participants had both
      reductions and increases in the amplitude of hemodynamic response in a variety of
      subcortical and cortical brain regions. These included regions involved in
      perception and attention such as the occipital and parietal lobes, motor cortex,
      anterior cingulate and prefrontal cortex. These findings suggest that estrogen
      may facilitate the efficiency of brain function during the performance of
      sustained attention tasks in post-menopausal elderly women.

PMID- 16084070
TI  - Production of a bioflocculant by Aspergillus parasiticus and its application in
      dye removal.
AB  - Aspergillus parasiticus was found to produce a bioflocculant with high
      flocculating activity for Kaolin suspension and water-soluble dyes. Results
      showed that the carbon and nitrogen sources favorable for the production of the
      bioflocculant were corn starch and peptone, and an optimal condition of 28
      degrees C, initial pH 5-6 and shaking speed of 150 rpm. The highest flocculating
      efficiency achieved for Kaolin suspension was 98.1%, after 72 h cultivation. The
      bioflocculant was mainly composed of sugar (76.3%) and protein (21.6%), and an
      average molecular weight of 3.2x10(5) Da. X-ray photoelectron spectroscopy (XPS)
      and Fourier transform infrared (FTIR) spectra showed that amino, amide and
      hydroxyl groups were present in the bioflocculant molecules. The bioflocculant
      was effective in flocculating some soluble anionic dyes in aqueous solution, in
      particular Reactive Blue 4 and Acid Yellow 25 with a decolorization efficiency of
      92.4 and 92.9%, respectively. The decolorization efficiency was dependent on the
      flocculant dosage and solution pH. XPS result shows that the amine groups in the
      bioflocculant were protonated at pH 5, and thus the positive bioflocculant was
      attracted to the negatively charged dye molecules. The amino and amide groups in
      the bioflocculant molecule are believed to play an important role in flocculation
      from the viewpoint of electrostatic interaction.

PMID- 16084071
TI  - [Vitamin D status in Gabonese children].
AB  - OBJECTIVE: To analyse the status of vitamin D and the influence of a supplement
      of vitamin D in neonates and infants during the first 6 months of life in the
      african equatorial environnement of Gabon. DESIGN: Clinical (weight, height, head
      circumference, and diseases) and biological (calcemia, phosphatemia, serum
      alkaline phosphatase activity and plasma 25-hydroxyvitamin D levels) parameters
      were compared between 2 groups of children: group 1: 41 infants receving a daily
      supplement of 1000 IU of vitamin D, and group 2: 38 infants without vitamin D
      supplement. RESULTS: No significant differences were observed between the 2
      groups concerning clinical and biological parameters. In particular plasma levels
      of 25-hydroxyvitamin D were normal and similar in both groups. CONCLUSION: A
      vitamin D supplement appears to be useless in 0 to 6 months infants living in
      Gabon.

PMID- 16084072
TI  - [Use of human recombinant erythropoietin in children with cancer].
AB  - Eighty percent of children with cancer suffer from anemia at the time of
      diagnosis. The physiopathology of anemia is complex. Although anemia can be life
      threatening, its consequences on the physical, psychological and social state of
      the child are often minimized. Blood transfusion is the main treatment of anemia:
      its efficacy is immediate but shortlasting, and it involves infectious and
      hemolytic risks. The human recombinant erythropoietin has been used for more than
      25-years, and is often prescribed to adults with cancer and anemia. The human
      recombinant erythropoietin rHuEPO is nowadays used when blood transfusion is
      contra-indicated because of religious or cultural considerations, although
      several promising studies have been conducted about rHuEPO and children with
      cancer since 1996: it might be soon the preferential alternative treatment to
      anemia in children with cancer.

PMID- 16084073
TI  - [Early spontaneous ileal perforations in preterm infants: report of 4 cases].
AB  - An ileal perforation occurred shortly after birth in 4 very premature newborns.
      Diagnosis was made on an abdominal distension with a pneumoperitoneum on X-ray.
      There were no biological, radiological nor histological signs of necrotizing
      enterocolitis. There were no digestive short- or long-term complications.
      According to the few authors who described this syndrome, there are some risk
      factors, but they were not clearly involved in our cases. Ileal perforation in
      the absence of signs of necrotizing enterocolitis is rarely reported but should
      be well known because of its good prognosis.

PMID- 16084074
TI  - [Proteinuria in school-age children at Brazzaville].

PMID- 16084075
TI  - [Newly immigrant adolescents health and quality of life in Belgium: screening and
      prevention in school medicine].
AB  - OBJECTIVES: Little is known so far about the health of newly immigrant
      adolescents. The present study aimed to evaluate their health and quality of life
      (QoL) and to reinforce prevention and health promotion in school medicine.
      METHODS: One hundred and fifty-eight adolescents (mean age: 15,4 years) from 37
      nationalities were included in the study in two health centers in Brussels. This
      study was carried out by medical records analysis and administration of a
      questionnaire about health and QoL (VSP-A) in several languages. RESULTS: The
      results showed adolescents in good physical health. Nevertheless their quality of
      life deteriorated over time in Belgium. The QoL was significantly lower for
      adolescents without social support: 48,0 (SD=13,5) vs 60,6 (SD=11,1) compared
      with adolescents with social support - i.e. with one resource person - on a scale
      from 0 to 100. Adolescents had many subjective health problems, like "the future"
      cited by half of them. CONCLUSION: This study shows the importance of developping
      a specific approach to newly immigrant adolescents health and the contribution of
      school medicine in the identification of biological, psychological and social
      needs and hightlights the preventive answers carried out by school medicine.

PMID- 16084076
TI  - Prognostic factors and causes of death in Korean patients with idiopathic
      pulmonary fibrosis.
AB  - The purpose of this study was to investigate the prognostic factors at initial
      presentation and the causes of death in Korean patients with idiopathic pulmonary
      fibrosis (IPF), which might be different report wise, in comparison to the
      western countries. A retrospective review of 88 patients (mean 60.3 years, 69
      male) was carried out and they were diagnosed as IPF positive. After diagnosis,
      the survival rate was 57% and 41% for third and fifth year, respectively (mean
      follow-up 39.1 months). Mortality was closely correlated with severe dyspnea at
      presentation (Hazard Ratio [HR], 2.6 per grade; p=0.015), lower initial forced
      vital capacity (HR, 1.7 per 10% predicted; p=0.004) and lower initial diffusing
      capacity of the lung (HR, 1.5 per 10% predicted; p=0.033). Treatment with
      specific drugs was ineffective against the survival when compared with
      symptomatic supportive care. Thirty-four patients (68%) died of worsened
      respiratory failure, seven (14%) died of infection and only one patient showed
      cardiovascular death. In conclusion, our study suggests that the severity of
      dyspnea and lung function tests at the time of diagnosis are the predictive
      factors for the survival of patients with IPF. In comparison to the reports from
      western countries, we observed that respiratory failure and pulmonary infection
      were more frequent causes of death, while cardiovascular death was rare in Korean
      patients with IPF.

PMID- 16084077
TI  - Effects of consecutive high-dose alcohol administration on the utilization of
      sulfur-containing amino acids by rats.
AB  - In this study, we attempted to evaluate changes in sulfur-containing amino acid
      (SCAA) metabolism after short-term high-dose alcohol ingestion. At the beginning
      of the study, six animals were sacrificed as the baseline group and then other
      animals in the experiment were consecutively gavaged with alcohol (30%, 3 g/kg)
      for 7 days. Animals (n=6 each) were subsequently sacrificed at the time points of
      Days 1 (Group E1), 3 (Group E3) and 7 (Group E7). Blood samples and selected
      tissues were collected at each time interval. SCAA, pyridoxal phosphate (PLP) and
      glutathione (GSH) levels were analyzed. Results showed that taurine levels of
      tissues (brain, liver, heart and kidneys) all declined after the ethanol
      intervention and continued to decrease in selected tissues except the brain
      during the experiment. Furthermore, the trends of plasma taurine and PLP contents
      were highly correlated (r=.98, P=.045). A similar utilization pattern of plasma
      taurine and PLP indicated that transsulfuration preferred taurine production to
      GSH synthesis. The trend of plasma taurine levels being positively correlated
      with PLP levels reveals that dramatic transsulfuration occurred to meet the
      urgent demand for taurine by brain cells. In conclusion, we reported that
      continual alcohol ingestion alters SCAA utilization, especially by depletion of
      taurine and hypotaurine and by elevation of S-adenosyl homocysteine in the
      selected organs.

PMID- 16084078
TI  - Effects of glutamine on adhesion molecule expression and leukocyte transmigration
      in endothelial cells exposed to arsenic.
AB  - This study evaluated whether glutamine (GLN) concentration was related to
      endothelial surface molecule expression and the migration of polymorphonuclear
      neutrophils (PMNs) through endothelial cells (ECs) stimulated by arsenic. Human
      umbilical vein endothelial cells (HUVECs) and PMNs were treated with different
      GLN concentrations (0, 300, 600 and 1000 microM) for 24 h. After that, we
      stimulated HUVECs for 3 h with 0.5 microM arsenic, and PMNs were allowed to
      transmigrate to ECs for 2 h. HUVEC surface expressions of cell adhesion molecules
      and integrin (CD11b) and interleukin (IL)-8 receptor expressions on PMNs were
      measured. The transendothelial migration of PMNs was also analyzed. The results
      showed that cell adhesion molecule (CAM) and integrin expressions in arsenic
      groups were higher than in those without arsenic. Among the arsenic groups, the
      expression of CAMs on ECs and CD11b, and IL-8 receptor on PMNs was lowest with 0
      microM compared with the other GLN concentrations. Vascular CAM-1 on ECs and
      CD11b on PMN expression were higher with 300 microM than with 600 and 1000 microM
      GLN. IL-8 secretions from ECs and PMNs were higher with 300 muM than with 600 and
      1000 microM GLN, and this was consistent with the expression of the IL-8 receptor
      on PMNs. Polymorphonuclear neutrophil transmigration was significantly higher
      with 300 muM GLN than with other GLN concentrations. These results suggest that
      ECs and PMNs were activated after arsenic stimulation. Cell adhesion molecule
      expressions on ECs and PMNs were suppressed in the absence of GLN. A low GLN
      concentration comparable to catabolic conditions resulted in higher adhesion
      molecule expression and greater transendothelial migration of neutrophils.
      Glutamine administration at levels similar to or higher than physiological
      concentrations reduced IL-8 and adhesion molecule expression; PMN transmigration
      was also decreased after stimulation with arsenic.

PMID- 16084079
TI  - Mechanisms and preclinical efficacy of silibinin in preventing skin cancer.
AB  - Eukaryotic cellular machineries including the genome face continuous challenge
      from environmental deleterious agents, as well as from the by products of their
      own metabolism. Our skin is the most important barrier. It protects us from
      xenobiotic and genotoxic agents including ultraviolet (UV) solar radiation and
      potential carcinogens, which are notorious for causing skin cancer. There is a
      rise in non-melanoma skin cancer (NMSC), which is diagnosed in more than a
      million people every year in the United States alone, and is also prevalent in
      the other Western countries. In addition to sunscreens, chemoprevention of skin
      cancer by natural non-toxic compounds is suggested as an effective strategy to
      prevent the incidence of skin cancer. Our extensive animal studies on silibinin,
      a non-toxic bioactive component in milk thistle, suggest that it has a strong
      potential to prevent skin cancer incidence, promotion and progression in response
      to chemical carcinogens and tumour promoters as well as UV radiation. Our data
      suggest that silibinin has multiple targets in the cell, and can be protective
      against the harmful effects of cytotoxic agents such as reactive oxygen species
      and inflammation. Further, silibinin modulates mitogenic and survival signalling,
      p53, Cip1/p21 and other cell cycle regulatory molecules to prevent UVB-induced
      skin carcinogenesis. Our ongoing studies also suggest the positive effect of
      silibinin on the repair of UVB-induced DNA damage in mouse skin. Overall, the
      protective efficacy of silibinin against skin cancer is supported by sound
      mechanistic rationale in animal and cell culture studies, and suggests its
      potential use for humans.

PMID- 16084080
TI  - The role of the specialist nurse in paediatric oncology in the United Kingdom.
AB  - National guidance in the United Kingdom on the provision of services for children
      and young people with cancer and their families has consistently emphasised the
      need for specialist nursing as central to the delivery of safe and effective
      care. The temptation when examining the role of the specialist nurse is to look
      at those posts that carry a recognised 'specialist' label. It is equally
      important, however, to look at the development of nursing practice across the
      speciality and at how this can be both supported and recognised. Nurses with
      specialist knowledge, skills and expertise in paediatric oncology are needed in
      positions where they are able to develop nursing practice, direct service
      development, lead nursing research, and guide education and training. Effective
      clinical leadership is essential at the point at which nursing care is delivered
      whether that is at the hospital bedside, in the clinic and day care unit, or in
      the family home.

PMID- 16084081
TI  - Biodegradation of pyridine in a completely mixed activated sludge process.
AB  - A potential bacterial culture (P1), isolated from garden soil and identified as
      Pseudomonas pseudoalcaligenes-KPN, was used as a starter seed to develop the
      biomass in a completely mixed activated sludge (CMAS) reactor and the system was
      evaluated for treatment of wastewater containing pyridine. The results of this
      study indicate that pyridine could be degraded efficiently at a loading of 0.251
      kg pyridine kg MLSS(-1) d(-1) (0.156 kg TOC kg MLSS(-1) d(-1)) and at an optimal
      hydraulic retention time (HRT) of 24 h. Pyridine was used as the sole source of
      carbon and nitrogen by the biomass. Ammonia-nitrogen (NH3-N) was formed due to
      the metabolism of the pyridine ring. In the present investigation, the
      performance of CMAS with reference to pyridine biodegradation and the bio-kinetic
      constants for the biodegradation of pyridine, in a continuous system, were
      computed. The results indicate that a CMAS system inoculated with P.
      pseudoalcaligenes-KPN, under optimum conditions of HRT and pyridine loading,
      gives a yield coefficient of (Y) 0.29, decay coefficient (Kd) 0.0011 d(-1),
      maximum growth rate constant (mumax) 0.108 d(-1) and saturation rate constant
      (Ks) 5.37 mg L(-1) for pyridine.

PMID- 16084082
TI  - Characterisation and biodistribution of two neutral 99mTc(CO)3 complexes with a
      tridentate ligand.
AB  - N-(2-Mercapto-propyl)-1,2-phenylenediamine (MPPDA) and N-beta-aminoethylglycine
      (AEG) were labelled with 99mTc(CO)3(+) to form the neutral complexes
      [99mTc(CO)3(MPPDA)] and [99mTc(CO)3(AEG)]. Both complexes were formed in
      excellent yields and their identity was confirmed by LC-MS. In mice, none of the
      new tracer agents showed brain uptake. [(99m)Tc(CO)3(MPPDA)] was trapped mainly
      in the liver and excreted via the hepatobiliary system, whereas [99mTc(CO)3(AEG)]
      was excreted rapidly via the kidneys to the urine.

PMID- 16084083
TI  - Design, synthesis and structure-activity relationship of a series of fragment
      analogues of antistasin (ATS) and ghilantens (GLS).
AB  - A series of low molecular weight peptide inhibitors of Factor Xa, fragment
      analogues of ATS and GLS, was designed and synthesized by the SPPS method. The
      new analogues included different basic amino acids in 109 position. In order to
      investigate the role of these factors, the newly synthesized peptides were tested
      for anticoagulant activity. To investigate the change in anticoagulant activity,
      new peptides were synthesized by replacement of the C-terminal COOH function with
      CONH2. The biological activity of all compounds was measured in respect to APTT
      (activated partial thromboplastin time) and IC50 values (the concentrations for
      doubling APTT clotting times of human plasma) were determined.

PMID- 16084084
TI  - Terminal antisense oligonucleotide modifications can enhance induced exon
      skipping.
AB  - Induction of specific exon skipping during the processing of the dystrophin gene
      transcript is being pursued as a potential therapy for Duchenne muscular
      dystrophy. Antisense oligonucleotides directed at motifs involved in pre-mRNA
      processing can manipulate dystrophin exon incorporation in the mature gene
      transcript. We have compared the exon skipping ability of
      oligodeoxyribonucleotides with compounds of the identical sequence incorporating
      2'-O-methyl modified bases. Antisense oligonucleotides composed entirely of 2'-O
      methyl modified bases on a phosphorothioate backbone were consistently more
      efficient at inducing exon skipping than comparable oligodeoxyribonucleotides.
      Chimeric antisense oligonucleotides, mixtures of unmodified and 2'-O-methyl
      modified bases, induced intermediate levels of exon skipping. In addition, we
      describe terminal modifications that may be incorporated into the 2'-O-methyl
      antisense oligonucleotides to further enhance efficiency of exon skipping. Our
      findings suggest that 2'-O-methyl antisense oligonucleotides should be considered
      for human clinical trials involving targeted exon skipping in dystrophin gene
      expression in preference to oligodeoxyribonucleotides.

PMID- 16084085
TI  - Peripheral nerve lesions associated with a dominant missense mutation, E33D, of
      the lamin A/C gene.
AB  - Some mutations of the lamin A/C gene may be responsible for a combination of
      distinct phenotypes, such as muscular dystrophy and peripheral neuropathy. We
      describe muscle and peripheral nerve lesions in a patient with a dominant lamin
      A/C missense mutation, E33D. Myopathic and neurogenic patterns coexisted on
      muscle biopsy specimens, whereas the peripheral nerve presented a mixture of
      axonopathy and Schwann cell hypertrophy. A few abnormal nuclei were found in
      muscle fibers and Schwann cells. Our morphological findings in this case attest
      to the predominant axonal damage, but suggest possible involvement of Schwann
      cells in neuropathies related to laminopathies.

PMID- 16084086
TI  - Quantification of mobility impairment and self-assessment of stiffness in
      patients with myotonia congenita by the physiotherapist.
AB  - We investigated test-retest reliability and responsiveness in two functional
      measuring instruments, Timed Up&Go (TUG) and Timed-Stands Test (TST), and in
      three self-assessment scales, Visual Analogue Scale (VAS), Borg's Category-Ratio
      Scale (BorgCR10) and Myotonia Behaviour Scale (MBS) when quantifying myotonic
      stiffness and mobility impairment. These methods were used in the assessment of
      treatment efficacy of mexiletine. Six male patients with myotonia congenita
      followed a standardised protocol with time scoring and rest on two occasions,
      with and without mexiletine. Time scoring of TUG and TST and self-assessments of
      stiffness were performed. A 14-day stiffness diary was used at home. Timed Up&Go
      and TST showed very good test-retest agreement (ICC=0.87-0.95) and significant to
      change (P=0.005 and 0.001, respectively). All self-assessment scales revealed
      excellent responsiveness and good test-retest reliability. The measurement
      instruments possess great capacity to detect functional impairment in the
      myotonia congenita patient group, and sensibility to identify true changes due to
      treatment. When considering the results, three instruments are favoured; Timed
      Up&Go and BorgCR10 for short, and MBS for long-term evaluations.

PMID- 16084087
TI  - Genetic background influences muscular dystrophy.
AB  - Mutations in the genes encoding dystrophin and its associated proteins, the
      sarcoglycans, lead to muscular dystrophy in humans and in mouse models. In the
      presence of identical gene mutations, the muscular dystrophy phenotype can be
      highly variable. Using a mouse model of limb girdle muscular dystrophy engineered
      with a null allele of gamma-sarcoglycan, we bred the identical gamma-sarcoglycan
      mutation into four different genetic backgrounds. We found that the gamma
      sarcoglycan mutation is least severe in the129SV/J (129) strain and most severe
      on the DBA 2J JAX (DBA) strain using quantitative measures of Evan's blue dye
      uptake, as a marker of membrane permeability defects, and hydroxyproline content,
      as a marker of fibrosis. In addition we show that the DBA mice are most severely
      affected regardless of gender and age. The enhanced phenotype observed in the DBA
      strain was not caused by exercise as the DBA mice scored the lowest in a
      voluntary activity test. The milder phenotype seen in the 129SV/J and C57B6/J
      strains suggests that these backgrounds contain modifier loci that partially
      suppress the muscular dystrophy phenotype. Identification of these modifier genes
      and the associated pathways may lead to novel therapeutic strategies.

PMID- 16084088
TI  - Subclinical semitendinosus and obturator externus involvement defines an
      autosomal dominant myopathy with early respiratory failure.
AB  - We recently described a dominant limb myopathy characterised by early respiratory
      failure whilst affected individuals were still ambulant (autosomal dominant
      myopathy with early respiratory failure). Early diagnosis and exclusion of this
      disorder is difficult because of the insidious onset in late adult life and the
      highly selective muscle involvement, both clinically and pathologically. We
      performed muscle magnetic resonance imaging on seven cases of autosomal dominant
      myopathy with early respiratory failure (age range 37-66 years, 4 male) and show
      selective early involvement of semitendinosus and obturator externus on magnetic
      resonance imaging that cannot be detected clinically, with different rates of
      progression in closely related muscles. These findings are specific to autosomal
      dominant myopathy with early respiratory failure and enable early non-invasive
      diagnosis for individuals at risk.

PMID- 16084089
TI  - Prenatal diagnosis in laminin alpha2 chain (merosin)-deficient congenital
      muscular dystrophy: a collective experience of five international centers.
AB  - The congenital muscular dystrophies (CMD) are clinically and genetically
      heterogeneous. The merosin (laminin alpha2 chain) deficient form (MDC1A), is
      characterized clinically by neonatal hypotonia, delayed motor milestones and
      associated contractures. It is caused by deficiency in the basal lamina of muscle
      fibers of the alpha2 chain of laminins 2 and 4 (LAMA2 gene at 6q22-23). Laminin
      alpha2 chain is also expressed in fetal trophoblast, which provides a suitable
      tissue for prenatal diagnosis in families where the index case has total
      deficiency of the protein. This article reports the collective experience of five
      centers over the past 10 years in 114 prenatal diagnostic studies using either
      protein analysis of the chorionic villus (CV) of the trophoblast plus DNA
      molecular studies with markers flanking the 6q22-23 region and intragenic
      polymorphisms (n=58), or using only DNA (n=44) or only protein (n=12) approaches.
      Of the 102 fetuses studied by molecular genetics, 27 (26%) were predicted to be
      affected while 75 (74%) were considered as unaffected, with 52 (51%) being
      heterozygous, thus conforming closely to an autosomal recessive inheritance. In
      18 of the 27 affected fetuses, the trophoblast was studied by immunocytochemistry
      and there was a total or only traces deficiency of the protein in CV basement
      membrane in all. In 10 cases material from the presumably affected fetus was
      available for analysis after termination of the pregnancy and immunohistochemical
      study confirmed the diagnosis in all of them. Prenatal studies of 'at risk'
      pregnancies in the five centers produced neither false negative (merosin
      deficiency in CVs in a normal fetus), nor false positive (normal merosin
      expression in CVs and affected child), indicating the reliability of the
      technique, when all the necessary controls are done. Our experience suggests that
      protein and DNA analysis can be used either independently or combined, according
      to the facilities of each center, to provide accurate prenatal diagnosis of the
      MDC1A, and have an essential role in genetic counseling.

PMID- 16084090
TI  - Ryanodine receptor 1 mutations, dysregulation of calcium homeostasis and
      neuromuscular disorders.
AB  - The skeletal muscle ryanodine receptor is an intracellular calcium release
      channel which plays a central role in excitation contraction coupling. At least
      80 mutations have been identified in the gene encoding the skeletal muscle
      ryanodine receptor and linked to several neuromuscular disorders, whose common
      feature appears to be a dysregulation of calcium homeostasis. A decade of
      research into the functional consequences of how these mutations affect the
      functional properties of the ryanodine receptor and their impact on disease, have
      significantly advanced our understanding of Malignant Hyperthermia, Central Core
      Disease and Multiminicore Disease. This review gives an overview of the important
      findings in the field of calcium homeostasis in skeletal muscle and describes how
      mutations in the ryanodine receptor gene might affect the function of this
      intracellular calcium release channel and lead to neuromuscular disorders.

PMID- 16084091
TI  - Phosphorylation and activation of STAT proteins by hypoxia in breast cancer
      cells.
AB  - Several constitutively activated signal transducers and activators of
      transcription (STAT) proteins have been observed in a wide number of human cancer
      cell lines and primary tumors. Normal cells maintain normoxic conditions but
      tumor cells are characteristically hypoxic. We studied the altered activation and
      tyrosine phosphorylation of STATs under hypoxic conditions (2% O2) or
      desferrioxamine (DFO) treatment in mouse mammary epithelial cells (HC11) and a
      human breast cancer cell line (MCF-7). STAT1, -3 and -5 proteins are especially
      important and are observed at elevated levels in tumorigenesis. We also
      investigated the serine phosphorylation of STAT1, -3, and -5 under hypoxic
      conditions or DFO treatment in HC11 and MCF-7 cells. Here we show that DFO or
      hypoxia stimulates the tyrosine and/or serine phosphorylation and the expression
      of STAT proteins in breast cancer cells. Our data suggest that DFO or hypoxic
      condition is a critical stimulator for the activation of STAT proteins in breast
      cancer cells. These results may provide the basis for identifying another
      mechanism of breast tumorigenesis via the JAK/STAT pathway in hypoxia. Also,
      activation of STAT proteins by hypoxia may play an important role in the
      physiological phenomenon of embryonic stem cells and old cells with hypoxic
      conditions.

PMID- 16084092
TI  - Cancer stem cells: lessons from leukemia.
AB  - A fundamental problem in cancer research is identification of the cell type
      capable of initiating and sustaining growth of the tumor--the cancer stem cell
      (CSC). While the existence of CSCs was first proposed over 40 years ago, only in
      the past decade have these cells been identified and characterized in
      hematological malignancies. Recent studies have now described CSCs in solid
      tumors of the breast and brain, raising the possibility that such cells are at
      the apex of all neoplastic systems. An appreciation of the biological
      distinctness of CSCs is crucial not only for the design of studies to understand
      how tumorigenic pathways operate but also for the development of specific
      therapies that effectively target these cells in patients.

PMID- 16084093
TI  - The spindle checkpoint: tension versus attachment.
AB  - The spindle checkpoint ensures the fidelity of chromosome segregation by
      preventing cell-cycle progression until all the chromosomes make proper bipolar
      attachments to the mitotic spindle and come under tension. Despite significant
      advances in our understanding of spindle checkpoint function, the primary signal
      that activates the spindle checkpoint remains unclear. Whereas some experiments
      indicate that the checkpoint recognizes the lack of microtubule attachment to the
      kinetochore, others indicate that the checkpoint senses the absence of tension
      generated on the kinetochore by microtubules. The interdependence between tension
      and microtubule attachment make it difficult to determine whether these signals
      are separable. In this article (which is part of the Chromosome Segregation and
      Aneuploidy series), we consider recent evidence that supports and opposes the
      hypothesis that defects in tension act as the primary checkpoint signal.

PMID- 16084094
TI  - PINCH, N(i)ck and the ILK: network wiring at cell-matrix adhesions.
AB  - Cell-extracellular-matrix adhesion and communication are mediated by integrins
      and a complex network of proteins that link integrins to the actin cytoskeleton.
      In this article, I discuss recent evidence that indicates that PINCH-1 and
      integrin-linked kinase (ILK), which form a tight complex in cells, serve as one
      of the hubs in the integrin-actin network. This hub mediates many protein
      interactions with a wide range of affinities (K(D) ranging from >10(-3)M to <10(
      7)M). Furthermore, many of these interactions are evolutionally conserved and
      functionally indispensable for maintaining the integrity of and signaling through
      the integrin-actin network. Consequently, loss of the PINCH-1-ILK complex is
      disastrous for embryogenesis in vertebrates and invertebrates. By contrast,
      aberrance of individual interactions contributes to diverse defects. Dissecting
      the interactions and functions that are mediated by the PINCH-1-ILK complex
      presents an exciting challenge and an opportunity to unravel the structure and
      functions of the integrin-actin network.

PMID- 16084096
TI  - CREB: the unindicted cancer co-conspirator.
AB  - The transcription factor cAMP response-element binding protein (CREB)
      participates in a diverse array of cellular processes, including survival,
      proliferation and glucose metabolism. A new report by Shankar et al. shows that
      patients with acute myeloid leukemia (AML) have a greater incidence of relapse
      when intracellular levels of CREB are elevated. By enhancing expression of
      certain cell-cycle genes, CREB appears to promote growth-factor-independent
      proliferation and survival of myeloid cells. The results provide new insights
      into CREB function and suggest potential avenues for therapeutic intervention.

PMID- 16084095
TI  - Chemical approaches for investigating phosphorylation in signal transduction
      networks.
AB  - The power and scope of chemical synthesis offer considerable opportunities to
      broaden the lexicon of chemical tools that can be implemented for the study of
      complex biological systems. To investigate individual signaling proteins and
      pathways, chemical tools provide a powerful complement to existing genetic,
      chemical genetic and immunologic methods. In particular, understanding
      phosphorylation-mediated signaling in real time yields important information
      about the regulation of cellular function and insights into the origin of
      disease. Recent advances in the development of photolabile caged analogs of
      bioactive species and fluorescence-based sensors of protein kinase activities are
      useful for investigating protein phosphorylation and the roles of
      phosphoproteins. Photolabile caged analogs allow spatial and temporal control
      over the release of a compound, while fluorescence-based sensors allow the real
      time visualization of kinase activity. Here, we discuss recent advances that have
      increased the specificity and availability of these tools.

PMID- 16084097
TI  - Synthesis and evaluation of a DHA and 10-hydroxycamptothecin conjugate.
AB  - We have synthesized a conjugate of cis-4,7,10,13,16,19-docosahexenoic acid (DHA)
      and 10-hydroxycamptothecin (HCPT), DHA-HCPT. The antitumor activity of DHA-HCPT
      was evaluated in vitro against L1210 leukemia cells and in experimental animal
      tumor models including L1210 leukemia, Lewis lung carcinoma, and colon 38
      adenocarcinoma. DHA-HCPT showed a greatly improved antitumor efficacy compared to
      HCPT.

PMID- 16084098
TI  - Amentoflavone and its derivatives as novel natural inhibitors of human Cathepsin
      B.
AB  - Cathepsin B (CatB) is a member of the papain superfamily of cysteine proteases
      and has been implicated in the pathology of numerous diseases, including
      arthritis and cancer. Amentoflavone is found in a number of plants with medicinal
      properties, including Ginkgo biloba and Hypericum perforatum (St. John's Wort).
      Herein, we report the structure-activity relationship (SAR) and binding mechanism
      of three biflavones, amentoflavone (AMF1), 4'''-methylamentoflavone (AMF2) and
      7'',4'''-dimethylamentoflavone (AMF3), isolated from Taxodium mucronatum by us as
      novel natural inhibitors of human CatB with strong inhibitory activities at IC50
      values of 1.75, 1.68 and 0.55muM, respectively. Density functional theory (DFT)
      method was applied to optimize the geometry structures of AMF1, AMF2 and AMF3 at
      the B3LYP/6-31G* level. FlexX was explored to dock the three biflavones to the
      binding sites of CatB, and to get a better understanding of vital interactions
      between these biflavones and CatB. A good correlation between the calculated
      quantum descriptors and the experimental inhibitory activities suggested that
      quantum model of these potential inhibitors is reliable. Through geometry and
      electron structure analysis of AMFs, it was observed that the CH3 substitute at
      7'' and 4''' positions could not vary the difference in geometry structure
      significantly, but increase the electron density of A-ring, HOMO energy,
      hydrophobic property, and improve inhibitory activity. Structural and energetic
      analysis of AMFs and AMFs-CatB complexes showed that the electron-donor site is
      the A-ring, which shows the highest HOMO energy distribution, and the electron
      acceptor site is the F-ring, which shows the highest LUMO energy distribution in
      AMFs, and the pi-pi interaction between A-ring and residue Trp221, two hydrogen
      bonds (O5 and Trp221; O4 and Gln23 ), hydrophobic interaction between the C-ring
      and residue Cys29 and CH3 substitutes at 7'' and 4''' might play a crucial role
      in the inhibition of AMFs on CatB. Results indicated that AMFs are new natural
      reversible inhibitors that would be useful in developing potent inhibitors of
      CatB.

PMID- 16084099
TI  - Metabolism of pentacarboxylate porphyrinogens by highly purified human
      coproporphyrinogen oxidase: further evidence for the existence of an abnormal
      pathway for heme biosynthesis.
AB  - An abnormal series of porphyrin tetracarboxylic acids known as the
      isocoproporphyrins, are commonly excreted by patients suffering from the disease
      porphyria cutanea tarda (PCT). These porphyrins appear to arise by bacterial
      degradation of dehydroisocoproporphyrinogen that is generated by the premature
      metabolism of the normal pentacarboxylate intermediate (5dab) by
      coproporphyrinogen oxidase (copro'gen oxidase). This porphyrinogen can be further
      metabolized by uroporphyrinogen decarboxylase to give harderoporphyrinogen, one
      of the usual intermediates in heme biosynthesis. Therefore, it is possible that
      some of the heme formed under abnormal conditions may originate from the
      'isocopro-type' porphyrinogen intermediate. In order to investigate the
      feasibility of alternative pathways for heme biosynthesis, the four type III
      pentacarboxylate isomeric porphyrinogens were incubated with purified, cloned
      human copro'gen oxidase at 37 degrees C with various substrate concentrations
      under initial velocity conditions. Of the four isomers, only 5dab was a substrate
      for copro'gen oxidase and this gave dehydroisocoproporphyrin. The structure of
      the related porphyrin tetramethyl ester was confirmed by proton NMR spectroscopy
      and mass spectrometry. The K(m) value for proto'gen-IX formation from copro'gen,
      an indicator of molecular recognition, was similar to the K(m) value for
      monovinyl product formation with 5dab, although copro'gen-III has an
      approximately twofold higher K(cat) value. Although 5dab is a slightly poorer
      substrate than copro'gen-III, these results support the hypothesis that an
      abnormal route for heme biosynthesis is possible in humans suffering from PCT or
      related syndromes such as hexachlorobenzene poisoning.

PMID- 16084100
TI  - Synthesis and antitrichinellosis activity of some 2-substituted-[1,3]thiazolo[3,2
      a]benzimidazol-3(2H)-ones.
AB  - Some new thiazolo[3,2-a]benzimidazolone derivatives were synthesized using two
      methods. The structures of the synthesized compounds were proved by means of IR,
      (1)H NMR and mass spectral data. Ab initio computations were performed in order
      to determine the electronic structure and geometry of the investigated molecules
      and to compare it to the geometry of albendazole. Biologically, experiments in
      vitro and in vivo were accomplished in order to identify the efficacy of the
      obtained thiazolobenzimidazolones against Trichinella spiralis. The effectiveness
      of compounds 4a-c in the intestinal phase of trichinellosis was 100% and in the
      muscle phase were 88% and 80% at a concentration of 100mg/kg mw for the compounds
      4a and 4c. The results of the hepatotoxicity test showed that the compounds 4a
      and 4b possess hepatotoxicity comparable to that of albendazole.

PMID- 16084101
TI  - Synthesis and biological evaluation of new tetrahydro-beta-carbolines as
      inhibitors of the mitotic kinesin Eg5.
AB  - The mitotic kinesin Eg5 (or KSP) is a crucial player in the development and
      function of the mitotic spindle. Inhibition of this protein leads to cell cycle
      arrest and apoptosis without interfering with other microtubule-dependent
      processes. Therefore, it is a potential target in cancer therapy. Here, we report
      the synthesis and biological evaluation of a small library of molecules based on
      the structure of the known Eg5 inhibitor HR22C16. One of these derivatives
      (compound trans-24) proved to be a potent and specific Eg5 inhibitor.

PMID- 16084102
TI  - 4-Alkyliden-beta-lactams conjugated to polyphenols: synthesis and inhibitory
      activity.
AB  - A series of compounds combining the beta-lactam and polyphenol scaffold have been
      prepared and evaluated for inhibition of human leukocyte elastase and matrix
      metallo-proteases MMP-2 and MMP-9. The design of these compounds has been based
      on the 'overlapping-type' strategy where two pharmacophores are linked in a
      single molecule. The most powerful compound against elastase was an N-galloyl-4
      alkyliden beta-lactam, [3-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-1
      (3,4,5-tris-benzyloxy-benzoyl)-azetidin-2-ylidene]-acetic acid ethylester, with
      an IC50 of 0.5 microM; while the most powerful against MMP-2 was a 4-alkyliden
      beta-lactam arylated on the C-3 hydroxy side chain (3,5-bis-benzyloxy-4-hydroxy
      benzoic acid 1-(2-benzyloxycarbonylmethylene-4-oxo-azetidin-3-yl)-ethyl ester)
      with an IC50 of 4 microM. Of the total 35 compounds tested, high levels of
      inhibition of elastase and of MMPs were separately exerted by distinct molecules.

PMID- 16084103
TI  - Highly anisotropic distribution of iron nanoparticles within MCM-41 Mesoporous
      Silica.
AB  - Electron microscopy techniques are used to visualize the spatial distribution of
      iron nanoparticles inside a mesoporous MCM-41 molecular sieve. Direct observation
      of the iron oxide nanoparticles by STEM-HAADF imaging reveals a highly non
      uniform spatial distribution inside the mesopores. These particles are retained
      in the pores after a reduction treatment unlike the behavior found in other
      similar systems. It is found that thermal treatments induce changes in its
      morphology, creating nanowires from particle strings.

PMID- 16084104
TI  - Mutations in neurofilament genes are not a significant primary cause of non-SOD1
      mediated amyotrophic lateral sclerosis.
AB  - While 1 to 2% of amyotrophic lateral sclerosis (ALS) is caused by mutations in
      the SOD1 gene, the basis of the remaining instances of inherited disease is
      unknown. Neuropathology, mouse modeling, and human genetics have implicated
      neurofilaments in the pathogenesis of motor neuron diseases such as ALS and
      Charcot-Marie-Tooth disease (CMT). A systematic analysis of the coding region and
      intron-exon boundaries of all three neurofilament genes is now reported from DNA
      samples derived from more than 200 non-SOD1 linked familial and sporadic ALS
      patients, along with >400 non-disease control individuals. Rare variants within
      each of the three neurofilament subunits that are predicted to affect
      neurofilament assembly properties were identified at higher frequency in non-SOD1
      mutant ALS samples. However, none could be unambiguously linked to dominantly
      inherited disease. Thus, mutations in neurofilaments are possible risk factors
      that may contribute to pathogenesis in ALS in conjunction with one or more
      additional genetic or environmental factors, but are not significant primary
      causes of ALS.

PMID- 16084105
TI  - Copper binding is the governing determinant of prion protein turnover.
AB  - The cellular isoform of the prion protein (PrP(c)) is located at the cell
      membrane, anchored externally by a glycosylphosphatidylinositol (GPI) anchor. It
      is a copper (Cu) binding glycoprotein with a rapid basal turnover. Previous
      studies have shown that exposure of cells to Cu causes internalisation of PrP(c)
      in vitro. In this study, we show that physiological levels of Cu promote
      internalisation of PrP(c). Interaction between PrP(c) and Cu was found to be the
      overriding factor in stimulating the internalisation response with other metals
      showing no effect. Deletion mutation studies have shown that two domains are
      essential for copper-induced internalisation to occur. These two domains are the
      octameric repeat region, encompassing amino acids 51-89, and the palindromic
      region, amino acids 112-119 with the sequence AGAAAAGA. The decrease in
      detectable levels of PrP(c) at the cell surface following Cu treatment was found
      to be the result of rapid internalisation rather than loss into the surrounding
      environment. These results have implications for both normal metabolism of PrP(c)
      and the possible mechanism of conversion of PrP(c) to PrP(sc).

PMID- 16084106
TI  - A fluorescence bioassay to detect residual formaldehyde from clinical materials
      sterilized with low-temperature steam and formaldehyde.
AB  - A microtiter plate toxicity test based on fluorescence was developed to determine
      the residual concentration of formaldehyde on medical items after LTSF
      sterilization. The residual formaldehyde on eight common materials, some of which
      are used in different clinical instruments and devices were analysed after
      sterilization with LTSF. Formaldehyde residues were detected on cotton, filter
      paper, natural rubber, PVC, and silicone-coated latex, but not on polyurethane,
      silicone or glass. Formaldehyde never exceeded the recommended maximum
      concentration on clinical devices of about 5 microg/cm2. The results were
      compared with those obtained by means of a chemical method, the correlation being
      good (R2=0.9396). The biological method proposed here is fast and can be
      automated, which means that it could be used as a screening method when there are
      doubts as to the accumulation of residues on clinical materials or instruments
      that are going to be sterilized with LTSF.

PMID- 16084107
TI  - Stable production of recombinant chicken antibody in CHO-K1 cell line.
AB  - When compared with mammalian IgG, chicken IgY is advantageous in terms of cross
      reactivity. In this study, two plasmids were constructed for expression of
      recombinant chicken IgY derived from a chicken hybridoma. The first was for
      expression of the light (L) chain, and the other was for the heavy (H) chain with
      a histidine (His) tag at the carboxy-terminal. After transfection of recombinant
      chicken IgY gene into Chinese hamster ovary cells, a transfectant designated HF33
      that secreted the specific antibody was selected. HF33 cells produced recombinant
      IgY with His tag at 10-15 microg/10(6) cells/24 h. On Western blotting analysis,
      the recombinant IgY was detected as one band for the H chain and two bands for
      the L chain. The recombinant IgY was successfully purified in a one-step
      procedure using a nickel-affinity resin. These results indicate that the present
      recombinant chicken IgY is useful for further applications.

PMID- 16084108
TI  - A sialylation-sensitive cell-based in vitro bioassay for erythropoietin;
      incorporation of the galactose-binding Erythrina crista-galli lectin.
AB  - The in vivo biological activity of erythropoietin (Epo) is dependent on its being
      adequately sialylated. Current in vitro bioassays for Epo do not correlate with
      the in vivo bioassays as the former do not take into account the role the liver
      plays in clearing desialylated glycoproteins from the circulation. Here we
      describe a sialylation-sensitive cell-based Epo bioassay. In the first instance,
      Epo activity in vitro was measured using proliferation of AS-E2 cells, and in
      vivo using the polycythaemic mouse bioassay. Activity in vivo was progressively
      abolished by controlled desialylation, whereas activity in vitro was essentially
      unaffected. Incorporation of an incubation step with a solid-phase galactose
      binding lectin (Erythrina crista-galli), effectively mimicking passage through
      the liver in vivo, renders the in vitro bioassay sensitive to desialylation, such
      that Epo desialylated almost to completion had <10% of the activity of untreated
      Epo. These studies offer proof of principle, that rational manipulation of in
      vitro bioassays can allow prediction of activity in vivo without the use of live
      animals.

PMID- 16084109
TI  - Conical tomography II: A method for the study of cellular organelles in thin
      sections.
AB  - We have used conical electron tomography in order to reconstruct neuronal
      organelles in thin sections of plastic embedded rat somato-sensory cortical
      tissue. The conical tilt series were collected at a 55 degrees tilt and at 5
      degrees rotations, aligned using gold particles as fiduciary markers, and
      reconstructed using the weighted back projection algorithm. After a refinement
      process based on projection matching, the 3D maps showed the "unit membrane
      pattern" along the entire reconstructed volume. This pattern is indicative of the
      bilayer arrangement of phospholipids in biological membranes. Based on Fourier
      correlation methods as well as the visualization of the "unit membrane" pattern,
      we estimated resolutions of approximately 4 nm. To illustrate the prospective
      advantages of conical tomography, we segmented "coated" vesicles in the
      reconstructed volumes. These vesicles were comprised of a central core enclosing
      a small lumen, and a protein "coating" extending into the cytoplasm. The "coated"
      vesicle was attached to the plasma membrane through a complex structure shaped as
      an arch where the ends are attached to the membrane and the crook is connected to
      the vesicle. We concluded that conical electron tomography of thin-sectioned
      specimens provides a powerful experimental approach for studying thin-sectioned
      neuronal organelles at resolution levels of approximately 4 nm.

PMID- 16084110
TI  - Single-particle tracking of oriC-GFP fluorescent spots during chromosome
      segregation in Escherichia coli.
AB  - DNA regions close to the origin of replication were visualized by the green
      fluorescent protein (GFP)-Lac repressor/lac operator system. The number of oriC
      GFP fluorescent spots per cell and per nucleoid in batch-cultured cells
      corresponded to the theoretical DNA replication pattern. A similar pattern was
      observed in cells growing on microscope slides used for time-lapse experiments.
      The trajectories of 124 oriC-GFP spots were monitored by time-lapse microscopy of
      31 cells at time intervals of 1, 2, and 3 min. Spot positions were determined
      along the short and long axis of cells. The lengthwise movement of spots was
      corrected for cell elongation. The step sizes of the spots showed a Gaussian
      distribution with a standard deviation of approximately 110 nm. Plots of the mean
      square displacement versus time indicated a free diffusion regime for spot
      movement along the long axis of the cell, with a diffusion coefficient of 4.3+/
      2.6x10(-5) microm2/s. Spot movement along the short axis showed confinement in a
      region of the diameter of the nucleoid ( approximately 800 nm) with an effective
      diffusion coefficient of 2.9+/-1.7x10(-5) microm2/s. Confidence levels for the
      mean square displacement analysis were obtained from numerical simulations. We
      conclude from the analysis that within the experimental accuracy--the limits of
      which are indicated and discussed--there is no evidence that spot segregation
      requires any other mechanism than that of cell (length) growth.

PMID- 16084112
TI  - Evidence that cerebral blood volume can provide brain activation maps with better
      spatial resolution than deoxygenated hemoglobin.
AB  - With the aim of evaluating the relative performance of hemodynamic contrasts for
      mapping brain activity, the spatio-temporal response of oxy-, deoxy-, and total
      hemoglobin concentrations were imaged with diffuse optical tomography during
      electrical stimulation of the rat somatosensory cortex. For both 6-s and 30-s
      stimulus durations, total hemoglobin images provided smaller activation areas
      than oxy- or deoxy-hemoglobin images. In addition, analysis of regions of
      interest near the sagittal sinus vein show significantly greater contrast in both
      oxy- and deoxy-relative to total hemoglobin, suggesting that oximetric contrasts
      have larger draining vein contributions compared to total hemoglobin contrasts
      under the given stimulus conditions. These results indicate that total hemoglobin
      and cerebral blood volume may have advantages as hemodynamic mapping contrasts,
      particularly for large amplitude, longer duration stimulus paradigms.

PMID- 16084111
TI  - Spatiotemporal brain maps of delayed word repetition and recognition.
AB  - Whole-head magnetoencephalography (MEG) was used to spatiotemporally map the
      brain response underlying episodic retrieval of words studied a single time
      following a long delay (approximately 40 min). Recognition following a long delay
      occurs as a strong, sustained, differential response, within bilateral, ventral,
      and lateral prefrontal cortex, anterior temporal and medial parietal regions from
      approximately 500 ms onward, as well as ventral occipitotemporal regions from
      approximately 700 ms onward. In comparison with previous tasks using multiple
      repetitions at short delays, these effects were centered within the same areas
      (anteroventral temporal and ventral prefrontal) but were shifted to longer
      latencies (approximately 500 ms vs. approximately 200 ms), were less left
      lateralized, and appear more in anterolateral prefrontal regions and less in
      lateral temporal cortex. Furthermore, comparison of correctly classified words
      with misclassified, novel and repeated words, suggests that these frontotemporal
      parietocingulate responses are sensitive to actual as well as perceived
      repetition. The results also suggest that lateral prefrontal regions may
      participate more in controlled effortful retrieval, while left ventral frontal
      and anterior temporal responses may support sustained lexicosemantic processing.
      Additionally, left ventromedial temporal sites may be relatively more involved in
      episodic retrieval, while lateral temporal sites may participate more in
      automatic priming.

PMID- 16084113
TI  - Diffusion tensor imaging in medial temporal lobe epilepsy with hippocampal
      sclerosis.
AB  - Interictal diffusion imaging studies in patients with medial temporal lobe
      epilepsy (MTLE) accompanied by hippocampal sclerosis (HS) have shown an increased
      diffusivity in the epileptogenic hippocampus. In this study, we wanted to explore
      the whole brain in order to determine if MTLE could have an impact on the
      organization and the architecture of a large cerebral network and to identify
      clinical factors that could mediate diffusion abnormalities. Diffusion tensor
      imaging (DTI) and statistical parametric mapping of the entire brain were
      performed in 35 well-defined MTLE patients and in 36 healthy volunteers. SPM
      analyses identified three abnormal areas: an increased diffusivity was detected
      in the epileptic hippocampus and the ipsilateral temporal structures associated
      with a decreased anisotropy along the temporal lobe, a decreased diffusivity was
      found in the contralateral non-sclerotic hippocampus, the amygdala, and the
      temporal pole, and finally, a decreased anisotropy was noted ipsilaterally in
      posterior extratemporal regions. Duration of epilepsy, age at onset, and the
      frequency of generalized tonic-clonic seizures or partial complex seizures did
      not correlate with the presence of diffusion abnormalities. Region of interest
      analysis in the hippocampus/parahippocampus demonstrated a correlation between
      lower ipsilateral diffusivity values and occurrence of epigastric aura and
      between higher anisotropy values in both hemispheres and history of febrile
      seizures. In conclusion, this study showed that diffusion abnormalities are not
      restricted to the pathologic hippocampus and involve a larger network. This
      pattern may indirectly reflect the epileptogenic network and may be interpreted
      as a cause or a consequence of epilepsy.

PMID- 16084114
TI  - Concurrent CBF and CMRGlc changes during human brain activation by combined fMRI
      PET scanning.
AB  - A novel approach for concurrent measurement of regional cerebral blood flow (CBF)
      and regional cerebral metabolic rate for glucose consumption (CMRGlc) in humans
      is proposed and validated in normal subjects during visual stimulation. 18F
      labeled fluorodeoxyglucose was administered during the measurement of CBF by
      continuous arterial spin labeled magnetic resonance imaging (MRI). Subsequent
      positron emission tomographic (PET) scanning demonstrated the distribution of
      labeled deoxyglucose during the MRI acquisition. An excellent concordance between
      regional CBF and regional CMRGlc during visual stimulation was found, consistent
      with previously published PET findings. Although initially validated using a
      brief, non-quantitative protocol, this approach can provide quantitative CBF and
      CMRGlc, with a broad range of potential applications in functional physiology and
      pathophysiology.

PMID- 16084115
TI  - Functional implications of hippocampal volume and diffusivity in mild cognitive
      impairment.
AB  - Hippocampal atrophy has been related to mild cognitive impairment (MCI) and early
      Alzheimer disease (AD), but the diagnostic significance of cross-sectionally
      determined hippocampal volumes is still ambiguous. Diffusion-Tensor-Imaging (DTI)
      in MCI patients revealed an association of microstructural changes in hippocampal
      areas with verbal memory decline. MRI volumetry and DTI were combined to
      investigate 18 MCI patients attending a memory clinic, and 18 carefully age- and
      gender-matched healthy controls. Neuropsychological testing, high resolution T1
      weighted volume MRI scans, and DTI scans with regions-of-interest in hippocampal
      areas were applied. Left hippocampal volume was significantly lower (-11%, P =
      0.02) in MCI patients than in control subjects. No significant differences were
      found for the right hippocampus (-4%). Mean diffusivity (MD) was significantly
      elevated in MCI patients vs. controls in left (+10%, P = 0.002) and right
      hippocampal areas (+13%, P = 0.02). Hippocampal volume and MD values were not
      significantly correlated. Combining left hippocampal volume and MD measures
      showed that lower left hippocampal volumes were associated with poor verbal
      memory performance particularly when co-occurring with high MD values. No
      comparable associations could be found regarding the right hippocampal formation
      and with respect to non-verbal memory function. The results demonstrate that
      microstructural abnormalities as revealed by DTI are very sensitive early
      indicators of hippocampal dysfunction. The combination of macro- and
      microstructural parameters in hippocampal areas could be promising in early
      detection of neurodegenerative processes.

PMID- 16084116
TI  - The functional neuroanatomy of coordinated orofacial movements: sparse sampling
      fMRI of whistling.
AB  - Whistling serves as a model for a skilful coordinated orofacial movement with
      sensorimotor integration of auditory and proprioceptive input. The neural
      substrate of whistling was investigated by sparse sampling functional MRI (fMRI)
      where the motor task occurred during a silent interval between successive image
      acquisitions to minimize task-related imaging artefacts. Whistling recruited a
      symmetrically represented neural network including primary motor and ventral
      premotor cortex (PMv), SMA, cingulate gyrus, basal ganglia, primary and secondary
      somatosensory cortex, amygdala, thalamus and cerebellum. A temporal analysis
      revealed higher activity of left sensory cortex, right PMv and cerebellum during
      late execution compared to initiation of whistling. Task-related signal changes
      in right PMv and right paravermal cerebellum were found to correlate with the
      amplitude of the whistle sound in a separate correlation analysis. The findings
      emphasize the role of ventral premotor cortex, cerebellum and somatosensory areas
      as integrators of afferent input within a distributed orofacial sensorimotor
      network.

PMID- 16084117
TI  - Recipes for the linear analysis of EEG.
AB  - In this paper, we describe a simple set of "recipes" for the analysis of high
      spatial density EEG. We focus on a linear integration of multiple channels for
      extracting individual components without making any spatial or anatomical
      modeling assumptions, instead requiring particular statistical properties such as
      maximum difference, maximum power, or statistical independence. We demonstrate
      how corresponding algorithms, for example, linear discriminant analysis,
      principal component analysis and independent component analysis, can be used to
      remove eye-motion artifacts, extract strong evoked responses, and decompose
      temporally overlapping components. The general approach is shown to be consistent
      with the underlying physics of EEG, which specifies a linear mixing model of the
      underlying neural and non-neural current sources.

PMID- 16084118
TI  - Adiabatic cross-polarization via intermediate dipolar-ordered state.
AB  - It is experimentally demonstrated that an adiabatic demagnetization
      remagnetization in the laboratory frame, where the Zeeman order of abundant
      nuclei is first adiabatically converted into the dipolar order, and then, into
      the Zeeman order of rare nuclei, can significantly increase polarization of rare
      nuclei compared to the conventional cross-polarization technique.

PMID- 16084119
TI  - Murine models of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by airflow
      limitation, that is not fully reversible, and that is associated with an abnormal
      inflammatory response of the airways and lungs to noxious particles and gases.
      The airflow limitation is caused by increased resistance of the small conducting
      airways and by decreased elastic recoil forces of the lung due to emphysematous
      destruction of the lung parenchyma. In vivo animal models can help to unravel the
      molecular and cellular mechanisms underlying the pathogenesis of COPD. Mice
      represent the most favored animal species with regard to the study of (both
      innate and adaptive) immune mechanisms, since they offer the opportunity to
      manipulate gene expression. Several experimental approaches are applied in order
      to mimic the different traits of COPD in these murine models. Firstly, the
      tracheal instillation of tissue-degrading enzymes induces emphysema-like lesions
      in the lung parenchyma, adding further proof to the protease-antiprotease
      imbalance hypothesis. Secondly, the inhalation of noxious stimuli, including
      tobacco smoke, sulfur dioxide, nitrogen dioxide, or oxidants such as ozone, may
      also lead to COPD-like lesions in mice, depending on concentration, duration of
      exposure and strainspecific genetic susceptibility. Thirdly, in transgenic mice,
      a specific gene is either overexpressed (non-specific or organ-specific) or
      selectively depleted (constitutively or conditionally). The study of these
      transgenic mice, either per se or in combination with the above mentioned
      experimental approaches (e.g. the inhalation of tobacco smoke), can offer
      valuable information on both the physiological function of the gene of interest
      as well as the pathophysiological mechanisms of diseases with complex traits such
      as COPD.

PMID- 16084120
TI  - Cytokine-activated bronchial epithelial cell pro-inflammatory functions are
      effectively downregulated in vitro by ciclesonide.
AB  - Ciclesonide, a new inhaled corticosteroid, is administered as a parent compound
      and converted in the airway mucosa into the active metabolite, desisobutyryl-(des
      )ciclesonide. A study was designed to evaluate the ability of ciclesonide to
      modulate pro-inflammatory functions of human bronchial epithelial cell (HBEC)
      primary cultures being converted into des-ciclesonide. HBECs were stimulated with
      interleukin (IL)-4 and tumour necrosis factor (TNF)-alpha (20 ng/mL) in the
      presence of ciclesonide and intercellular adhesion molecule (ICAM)-1 expression,
      granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-8 release
      evaluated respectively by FACS and ELISA. Ciclesonide (3 microM) significantly
      inhibited ICAM-1 expression by stimulated HBECs, already after 3h and still after
      48 h culture (p < 0.01). At all the concentrations tested ciclesonide inhibited
      ICAM-1 expression (p < 0.05). GM-CSF and IL-8 release by stimulated HBECs was
      also downregulated by ciclesonide (p < 0.05). All the ciclesonide activities
      tested appeared to be mainly due to a partial inhibition of the 'IL-4 + TNF-alpha
      induced' and little or no involvement of the 'constitutive' cell functions. Des
      ciclesonide was detected in 24 h culture HBEC supernatants using high-performance
      liquid chromatography, while no parental compound ciclesonide was present. These
      results show at cellular level the fast and prolonged activity of ciclesonide on
      pro-inflammatory functions of HBECs, a selective target of asthma therapy,
      involved in the activation of this new inhaled corticosteroid.

PMID- 16084121
TI  - Agonist-independent alteration in beta-adrenoceptor-G-protein-adenylate cyclase
      system in an equine model of recurrent airway obstruction.
AB  - We examined the inhibitory sympathetic beta-adrenergic mechanisms in peripheral
      lung, bronchi and trachea of an equine model of recurrent airway obstruction
      (RAO), to support the hypothesis that the beta-adrenergic receptor dysfunction is
      not only restricted to cell surface receptor density but rather encompasses a
      mechanistic defect apart from the receptor, to the intracellular signaling
      components. The non-asthmatic lung possessed 3.2-fold more beta-adrenergic
      receptors than bronchi (496 +/- 19.4 vs. 155.1+/- 19.6 fmol/mg protein; P < 0.01)
      and 6.2-fold higher than in the trachea (79.8 +/- 12.6 fmol/mg protein; P <
      0.001) (assessed by radioligand binding assays using (-)-[(125)I]
      iodocyanopindolol, ICYP) and in all tissues a greater proportion of the beta(2)-
      than the beta(1)-subtype (75-80%). The receptor density (B(max)) in lung
      parenchyma and bronchial membranes was 33 and 42%, respectively, lower (P <
      0.001) in RAO than in control animals, attributable to a decrease in the beta(2)
      subtype. This receptor down-regulation was accompanied with an attenuated
      coupling efficiency of the receptor to the stimulatory G(S)-protein (P < 0.05 vs.
      control). Concomitantly, activation of adenylate cyclase evoked by isoproterenol
      was significantly reduced in lung and bronchial membranes of animals with RAO,
      whereas effects of 10 microM GTP, 10mM NaF, 10 microM forskolin and 10 mM Mn(2+)
      were not altered. There was no difference in beta-adrenergic receptor density,
      G(S)-protein or adenylate cyclase coupling in the trachea between asthmatic and
      control animals. In conclusion, in stable asthma the pulmonary beta-adrenergic
      receptor-G(S)-protein-adenylate cyclase system is impaired, thus the pathologic
      process involves all signaling components, and due to its close similarity, this
      animal model seems to serve as a suitable model, at least partly, of chronic
      asthmatic patients.

PMID- 16084122
TI  - High follicular phase luteinizing hormone levels in young healthy BRCA1 mutation
      carriers: implications for breast and ovarian cancer risk.
AB  - BRCA1 mutation carriers have up to 80% life-time risk of developing breast cancer
      and 20-40% risk of developing ovarian cancer. High LH levels have been linked to
      increased risks of both breast and ovarian cancers in some studies and it is
      unknown whether gonadotropin levels are associated with BRCA1 mutation status.
      The aim of the study was to explore whether gonadotropin levels were associated
      with BRCA1 mutation status among healthy 40-year-old-women from hereditary breast
      cancer families. All women completed a questionnaire including information on
      reproductive factors and OC use. We measured height, weight, breast volumes, and
      plasma levels of LH, FSH, and estradiol (E2) once during menstrual cycle days 5
      10 and once again during cycle days 18-23 in 43 non-carriers from BRCA1 families,
      20 BRCA1 mutation carriers, and 101 women from non-BRCA1/2 families. The
      strongest predictors of high LH levels among BRCA1 mutation carriers and non
      carriers during cycle days 5-10 were being a BRCA1 mutation carrier (p=0.002),
      lack of current OC use (p=0.003), and being nulliparous (p=0.01), adjusted for
      age and menstrual cycle day when the samples were obtained. This association was
      seen both in non-OC users and current OC users but was only significant in the
      former group (p=0.005). Because of multiple analyses it is possible that our
      finding is a result of a Type 1 statistical error. After a permutation test the
      new adjusted p value in non-OC users was 0.05. FSH and E2 were similar in non
      carriers, BRCA1 mutation carriers and women from non-BRCA1/2 families. We found
      significantly elevated LH levels in the follicular phase among young healthy
      BRCA1 mutation carriers compared with non-carriers from BRCA1 families. This is a
      small study and confirmatory studies are warranted to establish whether elevated
      LH levels are part of the BRCA1 phenotype and may be manipulated in order to
      reduce cancer risks in BRCA1 mutation carriers.

PMID- 16084123
TI  - 3-Hydrogenkwadaphnin targets inosine 5'-monophosphate dehydrogenase and triggers
      post-G1 arrest apoptosis in human leukemia cell lines.
AB  - 3-Hydrogenkwadaphnin (3-HK) is a recently characterized daphnane-type compound
      isolated from Dendrostellera lessertii with high anti-tumor activity in animal
      models. Herein, we report on time- and dose-dependent effects of this compound on
      growth, differentiation, IMPDH inhibition, cell cycle and apoptosis of a panel of
      human leukemia cell lines (HL-60, K562 and Molt4). The drug decreased the growth
      of leukemia cells in less than 24 h of treatment. However, longer exposure times
      and/or higher concentrations were required to promote cell apoptosis. Cell cycle
      analysis revealed the accumulation of cells in their G1 phase as early as 12 h
      after drug exposure but sub-G1 population was recorded after 24 h. Occurrence of
      apoptosis was constantly accompanied by morphological (staining with DNA-binding
      dyes) and biochemical (DNA fragments) variations among drug-treated cells.
      Despite these observations, non-activated normal human PBL were insensitive to
      the drug action. In addition, treatment of PHA-activated PBL, K562, Molt4 and HL
      60 cells with a single dose of the drug for 24 h led to the inhibition of IMPDH
      activity by almost 37, 38, 44 and 50%, respectively. In contrast, no difference
      in IMPDH activities were seen between normal PBL and the drug treated PBL cells.
      Restoration of the depleted GTP concentration by exogenous addition of guanosine
      (25-50 microM) reversed the drug effects on cell growth, DNA fragmentation and
      apoptosis. Furthermore, the drug effects were potentiated by exogenous addition
      of hypoxanthine to the drug-treated cells. Reduction of the drug potency on the
      non-proliferative (retinoic acid treated) HL-60 cells by almost 40%, compared to
      the proliferative cells, clearly shows type II IMPDH as one of the main targets
      of the drug. These results suggest that 3-HK may be a powerful candidate for
      treatment of leukemia.

PMID- 16084124
TI  - Bedside, classroom and bench: collaborative strategies to generate evidence-based
      knowledge for nursing practice.
AB  - The rise of evidence-base practice (EBP) as a standard for care delivery is
      rapidly emerging as a global phenomenon that is transcending political, economic
      and geographic boundaries. Evidence-based nursing (EBN) addresses the growing
      body of nursing knowledge supported by different levels of evidence for best
      practices in nursing care. Across all health care, including nursing, we face the
      challenge of how to most effectively close the gap between what is known and what
      is practiced. There is extensive literature on the barriers and difficulties of
      translating research findings into practical application. While the literature
      refers to this challenge as the "Bench to Bedside" lag, this paper presents three
      collaborative strategies that aim to minimize this gap. The Bedside strategy
      proposes to use the data generated from care delivery and captured in the massive
      data repositories of electronic health record (EHR) systems as empirical evidence
      that can be analysed to discover and then inform best practice. In the Classroom
      strategy, we present a description for how evidence-based nursing knowledge is
      taught in a baccalaureate nursing program. And finally, the Bench strategy
      describes applied informatics in converting paper-based EBN protocols into the
      workflow of clinical information systems. Protocols are translated into reference
      and executable knowledge with the goal of placing the latest scientific knowledge
      at the fingertips of front line clinicians. In all three strategies, information
      technology (IT) is presented as the underlying tool that makes this rapid
      translation of nursing knowledge into practice and education feasible.

PMID- 16084125
TI  - Melatonin for sleep disturbances in Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Many patients with Parkinson's disease (PD) experience
      sleep-related symptoms. Studies in other populations indicate that melatonin can
      increase sleep efficiency, decrease nighttime activity, and shorten sleep
      latency, but there has been little research on the use of melatonin in PD. The
      purpose of this study was to compare the effects of two doses of melatonin to
      placebo on sleep, daytime sleepiness, and level of function in patients with PD
      who complained of sleep disturbances. PATIENTS AND METHODS: A multi-site double
      blind placebo-controlled cross-over trial was employed; 40 subjects completed the
      10-week protocol. There was a 2-week screening period, 2-week treatment periods,
      and 1-week washouts between treatments. Nocturnal sleep was assessed by
      actigraphy and diaries, whereas daytime sleepiness and function were assessed by
      the Epworth Sleepiness Scale (ESS), Stanford Sleepiness Scale (SSS), and General
      Sleep Disturbance Scale (GSDS). RESULTS: Repeated measures analysis of variance
      revealed a significant improvement in total nighttime sleep time during the 50 mg
      melatonin treatment compared to placebo. There was significant improvement in
      subjective sleep disturbance, sleep quantity, and daytime sleepiness during the 5
      mg melatonin treatment compared to placebo as assessed by the GSDS. CONCLUSIONS:
      Although we found a statistically significant improvement in actigraphically
      measured total sleep time on 50 mg melatonin compared to 5 mg or placebo, this
      small improvement (10 min) may not be clinically significant. However, the
      significant improvement found in subjective sleep disturbance suggests that these
      modest effects may be clinically relevant in this patient population.

PMID- 16084127
TI  - A rapid method for retrovirus-mediated identification of complementation groups
      in Fanconi anemia patients.
AB  - Fanconi anemia (FA) is a rare autosomal recessive disorder that results from
      mutations in at least 11 different genes. Recent studies have demonstrated that
      clinical progression of the disease may be influenced by inter- and intragenic
      variations, emphasizing the importance of identifying the complementation groups.
      In the present study we have employed bicistronic retrovirus vectors that
      coexpress FA-specific cDNAs for complementation groups A, C, F, and G, together
      with the enhanced green fluorescence protein (EGFP), allowing for specific
      analysis of transduced EGFP+ cells within bulk cultures by flow cytometry. In
      addition, the assay relies on the correction of the characteristic FA-associated
      G2/M arrest after treatment of cells with DNA-damaging agents, which is analyzed
      by flow cytometry. Results obtained with this assay matched the complementation
      groups known for 12 control lymphoblast cell lines tested. We report here the
      results obtained for 48 FA patients with unknown complementation groups using
      this new assay. Complementation groups were identified for 24 patients. We have
      identified mutations in the genes corresponding to the assigned complementation
      group in 23 samples. This assay has now been established in a standardized
      fashion for complementation assignments in FA patients and the subsequent
      directing of rapid mutation analysis in those patients.

PMID- 16084129
TI  - Malassezia Baillon, emerging clinical yeasts.
AB  - The human and animal pathogenic yeast genus Malassezia has received considerable
      attention in recent years from dermatologists, other clinicians, veterinarians
      and mycologists. Some points highlighted in this review include recent advances
      in the technological developments related to detection, identification, and
      classification of Malassezia species. The clinical association of Malassezia
      species with a number of mammalian dermatological diseases including dandruff,
      seborrhoeic dermatitis, pityriasis versicolor, psoriasis, folliculitis and otitis
      is also discussed.

PMID- 16084128
TI  - Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to
      fetal and neonatal mice.
AB  - Gene therapy by use of integrating vectors carrying therapeutic transgene
      sequences offers the potential for a permanent cure of genetic diseases by stable
      vector insertion into the patients' chromosomes. However, three cases of T cell
      lymphoproliferative disease have been identified almost 3 years after retrovirus
      gene therapy for X-linked severe combined immune deficiency. In two of these
      cases vector insertion into the LMO2 locus was implicated in leukemogenesis,
      demonstrating that a more profound understanding is required of the genetic and
      molecular effects imposed on the host by vector integration or transgene
      expression. In vivo models to test for retro- and lentiviral vector safety prior
      to clinical application are therefore needed. Here we present a high incidence of
      lentiviral vector-associated tumorigenesis following in utero and neonatal gene
      transfer in mice. This system may provide a highly sensitive model to investigate
      integrating vector safety prior to clinical application.

PMID- 16084131
TI  - Sirtuins (histone deacetylases III) in the cellular response to DNA damage--facts
      and hypotheses.
AB  - Histone deacetylases (HDAC) are an important member of a group of enzymes that
      modify chromatin conformation. Homologues of the yeast gene SIR2 in mammalian
      cells code type III histone deacetylases (HDAC III, sirtuins), dependent on
      NAD(+) and inhibited by nicotinamide. In yeast cells, Sir2 participates in
      repression of transcriptional activity and in DNA double strand break repair. It
      is assumed that certain sirtuins may play a similar role in mammalian cells, by
      modifying chromatin structure and thus, altering the accessibility of the damaged
      sites for repair enzymes. A relation between poly(ADP-ribosylation) and sirtuin
      function in cells with damaged DNA has been also postulated. Interconnections
      between NAD(+) metabolism, poly(ADP-ribosylation), DNA repair and gene expression
      should allow to modulate the cellular response to agents that damage DNA.
      Preliminary results, reviewed in this paper indicate that such possibility
      exists. We propose a hypothetical mechanism of sirtuin participation in DSB
      repair. It is based on the assumption that activation of PARP at the sites of DNA
      strand breaks leads to a local increase in nicotinamide concentration.
      Nicotinamide then inhibits sirtuins exactly at the site of DNA strand break. At
      present, however, there are no data directly confirming the effect of sirtuin
      inhibition on DSB repair processes in mammalian cells. Nevertheless, a connection
      between the acetylation status of histones and repair of DNA breaks has recently
      been found, indicating that all HDAC classes may modulate DNA repair processes.
      In addition, sirtuins exert an anti-apoptotic action in various cell types.
      Hence, it is possible to sensitise cells to apoptosis-inducing agents by sirtuin
      inhibitors.

PMID- 16084132
TI  - Optimization of protein identification from digests as analyzed by capillary
      isoelectric focusing-mass spectrometry.
AB  - Capillary isoelectric focusing (CIEF) is a high-resolution separation technique
      for the analysis of peptides and protein digests. When coupled to ion trap-mass
      spectrometry (CIEF-MS) the unique separation mechanism is combined with a highly
      efficient detection system. In an earlier report, we described aspects of
      separation and interfacing in connection to the analysis of a digest of set of
      standard proteins. Now, we report on different aspects of the process of protein
      identification. Sequest software parameters were optimized by using a standard
      protein digest. These settings were used for the analysis of periplasmic proteins
      from Escherichia coli. Since in CIEF peptides are focused according to their pI
      values, the mobilization time of a particular peptide is dependent on its pI
      value. Based on this relation, the identification of some peptides was
      facilitated. Furthermore, the Sequest settings that were used could be evaluated.
      In total, 159 proteins were identified in a single run.

PMID- 16084133
TI  - High-throughput solubility assay for purified recombinant protein immunogens.
AB  - A high-throughput assay is described for analysis of the solubility of purified
      recombinant proteins. The assay is based on affinity purification of proteins in
      the presence of chaotropic agents followed by a dilution and incubation step to
      investigate the solubility in the absence of high concentrations of such agents.
      The assay can be performed in a 96-well format, which makes it well suited for
      high-throughput applications. For 125 recombinant proteins expressed as part of
      an antibody-based proteomics effort, experimental solubility data were compared
      to calculated hydrophobicity values based on the amino acid sequence of each
      protein. This comparison showed only weak correlation between the theoretical and
      experimental values, which emphasizes the importance of experimental assays to
      determine the solubility of recombinant proteins.

PMID- 16084134
TI  - Downregulation of osteoblast Phex expression by PTH.
AB  - Human/murine X-linked hypophosphatemia is a dominant disorder associated with
      renal phosphate wasting and defective bone mineralization. This disorder results
      from mutations in the PHEX/Phex (Phosphate-regulating gene with homologies to
      endopeptidases on the X chromosome) gene, which is expressed in fully
      differentiated osteoblasts. The purpose of the present study was to assess
      whether PTH, a major regulator of bone development and turnover, modulates
      osteoblastic Phex expression. The effects of different concentrations of PTH (rat
      fragment 1-34) were determined on Phex mRNA and protein expression in vitro using
      MC3T3-E1 osteoblastic cells and mouse primary osteoblasts; and in vivo using 45
      day-old mice infused for 3 days with PTH. Phex mRNA levels were quantitated on
      Northern blots by densitometric analysis relative to GAPDH mRNA levels. Phex
      protein levels were analyzed by immunoprecipitation of 35S-methionine-labeled
      osteoblast lysates or by immunoblotting of calvaria membrane extracts using a
      polyclonal rabbit antiserum raised against a mouse Phex carboxy-terminal peptide.
      Fully differentiated MC3T3-E1 cells were incubated for 4 to 48 h with increasing
      concentrations of PTH (10(-11) to 10(-7) M). PTH inhibited Phex mRNA expression
      in both mineralizing and nonmineralizing osteoblast cultures in a dose- and time
      dependent manner with a maximal inhibition at 10(-7) M PTH after 24 h (15+/-7% of
      control levels, n=5, P<0.001). The PTH-mediated downregulation of Phex mRNA
      levels was associated with corresponding decreases in Phex protein synthesis and
      suppression at 10(-7) M PTH. Similar results were obtained with primary
      osteoblasts isolated from newborn mouse calvaria. Consistent with the in vitro
      findings, continuous PTH infusion to mice elicited decreases in Phex expression
      in calvaria. The effect of PTH was also assessed on matrix mineralization by
      mature MC3T3-E1 cells by measuring 45Ca accumulation in cell layers. PTH (10(-7)
      M) inhibited the initiation (57+/-2% of control levels, n=5, P<0.001) and the
      progression of matrix mineralization (75+/-1% of control levels, n=5, P<0.001).
      In summary, PTH inhibits osteoblastic Phex expression in vitro and in vivo. The
      downregulation of Phex expression by PTH in vitro is associated with inhibition
      of matrix mineralization, consistent with a role for Phex in bone mineralization.

PMID- 16084135
TI  - Angiotensin I-converting enzyme insertion/insertion genotype as a genetic risk
      factor for cardiovascular disease.

PMID- 16084137
TI  - Should we cross the valve: the risk of retrograde catheterization of the left
      ventricle in patients with aortic stenosis.

PMID- 16084139
TI  - Reply to Ogimoto, angiotensin-converting enzyme inhibitors as a new therapy for
      atrial fibrillation? Controversy (Am Heart J 2005;149:e19.).

PMID- 16084140
TI  - Reply to Al-Shaer, is atorvastatin more appropriate to use in combination with
      niacin than simvastatin in patients with the metabolic syndrome? (Am Heart J
      2005;149:e17.).

PMID- 16084141
TI  - Azithromycin on soluble cell adhesion molecules and markers of inflammation in
      survivors of an acute coronary syndrome.

PMID- 16084142
TI  - Assessing prognosis in heart failure: is hepatocyte growth factor the next B-type
      natriuretic peptide?

PMID- 16084143
TI  - Percutaneous coronary intervention-induced emboli during primary PCI for STEMI:
      too little, too much, or too late?

PMID- 16084144
TI  - Do stents reduce mortality compared with balloon angioplasty? A critical review
      of all the evidence.

PMID- 16084145
TI  - Inflammation and coronary artery disease.
AB  - Inflammation is now recognized as being pivotal in the pathogenesis of
      atherosclerosis. This review highlights key concepts in our current understanding
      of the role of inflammation in the initiation, progression, and complication of
      atherosclerosis. The role of various triggers and amplifiers and the innate and
      adaptive immunity in the cascade of inflammatory events are also presented.
      Progress in our understanding of the inflammatory pathways in atherosclerosis has
      provided further mechanistic insight into the clinical benefits of current
      medical therapy and may alter our future treatment and preventive strategies.

PMID- 16084146
TI  - A review of the oral direct thrombin inhibitor ximelagatran: not yet the end of
      the warfarin era...
AB  - Ximelagatran is a direct thrombin inhibitor that offers numerous potential
      advantages compared with traditional anticoagulants. It is given orally, has a
      rapid onset of action, does not require laboratory monitoring, and is not
      associated with immune-mediated thrombocytopenia. Numerous phase III trials with
      ximelagatran focusing on deep vein thrombosis prophylaxis and treatment, stroke
      prevention in patients with atrial fibrillation, and secondary prevention after
      acute myocardial infarction have been conducted. Results of these trials indicate
      that ximelagatran has similar efficacy and risk of bleeding compared with
      currently used anticoagulants. Accordingly, the potential of this agent to
      replace warfarin therapy for a variety of indications has been widely touted.
      Ximelagatran has already been approved in Europe for prophylaxis of venous
      thromboembolism in patients undergoing hip or knee surgery. However, an adverse
      effect of ximelagatran is liver enzyme elevation, which has been observed in 5%
      to 10% of patients with chronic administration of the drug. Although initially
      felt to be transient in nature, subsequent data presented to the Federal Drug
      Administration suggest a small but real risk of significant hepatotoxicity. These
      data led the advisory committee to the Federal Drug Administration to recommend
      against immediate approval of ximelagatran pending further information. The
      consistent results of completed trials with ximelagatran suggest that it has the
      potential to be used in many conditions that currently require treatment with
      warfarin and heparin products. The potential benefit that may be achieved by the
      replacement of these historically problematic narrow therapeutic index agents
      must be weighed against as yet undetermined long-term risks of hepatotoxicity.

PMID- 16084147
TI  - The clinical challenge of bridging anticoagulation with low-molecular-weight
      heparin in patients with mechanical prosthetic heart valves: an evidence-based
      comparative review focusing on anticoagulation options in pregnant and
      nonpregnant patients.
AB  - BACKGROUND: Recent labeling changes for enoxaparin, a low-molecular-weight
      heparin (LMWH), have prompted a reexamination of its role in patients with
      mechanical prosthetic heart valves (MPHVs). Healthcare providers are faced with
      the challenge of weighing favorable trial results with LMWHs and balancing their
      clinical experiences with these agents as a bridge to oral anticoagulation in
      patients with prosthetic heart valves. This review will provide evidence-based
      guidance on issues surrounding the use of LMWH that require bridging
      anticoagulant therapy in the setting of cardiac surgery (MPHVs), cardiovascular
      disease, and during temporary interruption of oral anticoagulants in patients
      requiring periprocedural bridging therapy. METHODS: A Medline search was
      conducted of articles appearing in the medical literature published in English
      between 1992 and 2004. Approximately 120 clinical trials, case reports,
      editorials, and/or guideline statements were retrieved and reviewed by the
      authors as to their relevance for the subject under review, ie, bridging
      anticoagulation in patients with MPHVs. Approximately 80 of these publications
      were selected for detailed review, analysis, and discussion in a consensus
      format. RESULTS: This review addresses the controversy surrounding the divergence
      between the new labeling recommending against the use of LMWH in patients with
      MPHVs as well as the ongoing clinical experience and evidence in the medical
      literature. The clinical challenges in the use of LMWH and unfractioned heparin
      (UFH) in pregnant patients with MPHVs are presented; the evidence for LMWHs in
      nonpregnant patients with prosthetic valves is described; and the role of LMWH
      for bridging immediately after mechanical valve surgery and its periprocedural
      and perioperative uses are discussed. Based on an expert consensus panel,
      clinical algorithms for the use of LMWH in pregnant and nonpregnant patients with
      MPHVs are also illustrated. CONCLUSIONS: Based on the available data sets,
      clinical trials, reviews, and registry data, the evidence suggests that LMWH
      compared to UFH may be a safe and effective agent in patients with MPHVs. Future
      large-scale, randomized trials are warranted.

PMID- 16084148
TI  - Management of risk in peripheral artery disease: recent therapeutic advances.
AB  - Peripheral artery disease (PAD) is a problem frequently encountered by physicians
      who care for patients with coronary heart disease, diabetes mellitus, renal
      insufficiency, congestive heart failure, or stroke. Patients with PAD are at
      heightened risk of myocardial infarction and stroke and are 6 times more likely
      to die of cardiovascular causes than persons without the disease. There is an
      urgent need for therapies that reduce the incidence of vascular complications
      among patients with PAD. In recent years, a number of risk-lowering therapies
      have been validated by randomized controlled trials enrolling large numbers of
      patients with PAD. The available evidence supports aggressive lifestyle
      modification as well as the provision of an antiplatelet agent, an HMGCoA (3
      hydroxy-3-methylglutaryl coenzyme A) reductase inhibitor, and an angiotensin
      converting enzyme inhibitor for cardiovascular protection in patients with PAD.
      As a result of their high baseline risk and the proven effectiveness of these
      interventions, most patients with PAD will benefit substantially from aggressive
      medical therapy.

PMID- 16084149
TI  - Is it time to prescribe statins to patients with calcified aortic stenosis?
AB  - Aortic stenosis (AS) is a common disease especially in the older population. It
      is associated with high mortality and morbidity. Recent data suggest that
      coronary artery disease and AS share common risk factors. Retrospective studies
      suggest that statins might slow the progression of AS but there are no randomized
      clinical trial data available. It would seem that statins can be considered for
      medical treatment of AS; however, this needs to be investigated in future
      randomized clinical trials.

PMID- 16084150
TI  - Tezosentan in patients with acute heart failure: design of the Value of
      Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study
      (VERITAS).
AB  - BACKGROUND: Endothelin 1 is a potent endogenous vasoconstrictor neurohormone, and
      endothelin 1 plasma concentrations predict adverse outcomes in patients with
      acute heart failure (AHF). Tezosentan, an intravenous endothelin receptor
      antagonist, improved hemodynamics in patients with AHF; however, its effects on
      morbidity and mortality have not been evaluated. METHODS: The VERITAS program
      consists of 2 identical, double-blind, randomized, placebo-controlled,
      concurrently conducted trials (VERITAS-1 and VERITAS-2), performed in 150 centers
      in Europe, Israel, Australia, and North America. The program is designed to
      enroll at least 1760 patients hospitalized with dyspnea at rest because of AHF
      requiring intravenous therapy. In addition to conventional therapy, patients are
      randomized to receive tezosentan (5 mg/h for 30 minutes, then 1 mg/h for 24-72
      hours) or matching placebo. The 2 prespecified primary end points are the
      incidence of death or worsening heart failure at 7 days in the combined studies
      and the change from baseline in dyspnea over the first 24 hours of treatment,
      measured using a visual analog scale in VERITAS-1 and VERITAS-2, individually.
      RESULTS: Enrollment started in April 2003, and the program was discontinued in
      November 2005 because of the low probability of achieving a significant treatment
      effect. CONCLUSIONS: No currently available agents have been shown in a
      prospective, randomized, clinical trial to improve outcomes in patients with AHF.
      Thus, the VERITAS program will provide valuable insights into the effect of
      tezosentan on clinical outcomes in patients with AHF, as well as hemodynamics and
      clinical symptoms.

PMID- 16084151
TI  - Depression and ischemic heart disease: what have we learned so far and what must
      we do in the future?

PMID- 16084152
TI  - Tenecteplase and tirofiban in ST-segment elevation acute myocardial infarction:
      results of a randomized trial.
AB  - BACKGROUND: The combination of older reduced-dose fibrinolytic agents and
      platelet glycoprotein IIb/IIIa inhibitors has shown modest improvements in
      reperfusion and more striking improvements in ST-segment resolution after acute
      myocardial infarction. We performed a multicenter dose-ranging study of reduced
      doses of a newer fibrinolytic (tenecteplase) combined with tirofiban, a
      glycoprotein IIb/IIIa inhibitor. METHODS: The first goal of the trial was to
      identify a dose or doses of tirofiban that, when combined with reduced-dose
      tenecteplase, would result in a higher incidence of Thrombolysis In Myocardial
      Infarction (TIMI) grade 3 flow at 60 minutes versus full-dose tenecteplase alone.
      The second goal was to assess whether the optimum dose(s) from the first stage
      also would result in greater resolution of ST-segment elevation. RESULTS: In all,
      409 patients aged 18 to 75 years with myocardial infarction were enrolled. The
      incidence of TIMI grade 3 flow at 60 minutes did not differ significantly among
      dose groups, ranging from 50% to 68%. The corrected TIMI frame count likewise did
      not differ substantially (range 34-42). More patients given combined therapy had
      complete resolution of ST-segment elevation at 60 minutes compared with patients
      given tenecteplase alone. Major bleeding was infrequent, and no strokes occurred.
      Based on angiographic results of the first stage, the second planned stage of the
      study was not performed. CONCLUSIONS: Although combination therapies were not
      associated with increased reperfusion compared with full-dose tenecteplase alone,
      similar TIMI flow grades were achieved despite reductions in tenecteplase doses.
      ST-segment resolution was more rapid and complete with combination therapy versus
      full-dose tenecteplase, suggesting enhanced microcirculatory perfusion to the
      infarct zone in this dose-ranging trial.

PMID- 16084153
TI  - The relationship between baseline risk and mortality in ST-elevation acute
      myocardial infarction treated with pharmacological reperfusion: insights from the
      Global Utilization of Strategies To open Occluded arteries (GUSTO) V trial.
AB  - BACKGROUND: We studied the potential interaction between baseline risk of death
      and treatment with either standard fibrinolytic monotherapy or combination fibrin
      and platelet lysis with respect to outcome of patients with ST-elevation
      myocardial infarction (STEMI) enrolled in the Global Utilization of Strategies To
      open Occluded arteries (GUSTO) V trial. METHODS: Using the Thrombolysis in
      Myocardial Infarction (TIMI) risk score (0-14 points) for STEMI, we analyzed the
      30-day and 1-year mortality according to treatment assignment and risk category.
      Multivariable analysis was performed to identify the potential interactions
      between treatment and baseline risk. RESULTS: The TIMI risk score could be
      calculated in 16256 patients (98% of patients enrolled). The median score was 2
      (1-4) in each treatment group (P = .07). The risk score was significantly
      associated with 30-day mortality (hazard ratio [HR], 1.52; 95% CI 1.47-1.56, P <
      .001, for each additional 1 point), as well as with 1-year mortality (HR 1.51, CI
      1.47-1.55, P < .001). The treatment allocation was not significantly related to
      mortality, and there was no significant interaction between baseline risk score
      and treatment with respect to either end point. Although combination therapy
      significantly reduced death or reinfarction at 7 days (HR 0.69, CI 0.54-0.89, P <
      .01), independent of the risk score, there was no significant statistical
      interaction between the two (P = .29). CONCLUSION: The TIMI risk score accurately
      predicted early and 1-year mortality in patients with STEMI treated with
      pharmacological reperfusion. We did not identify any heterogeneity in the
      response of patients to combination therapy according to their TIMI risk score.

PMID- 16084154
TI  - Cereal fiber and whole-grain intake are associated with reduced progression of
      coronary-artery atherosclerosis in postmenopausal women with coronary artery
      disease.
AB  - BACKGROUND: Higher intake of fiber, especially cereal fiber, has been associated
      with reduced risk of cardiovascular events and mortality. However, there are
      limited data on the effect of fiber intake on measures of progression of coronary
      artery disease (CAD). The aim was to examine the association between intakes of
      total fiber and fiber from different dietary sources and progression of coronary
      artery atherosclerosis among women with established CAD. METHODS: A prospective
      cohort study involved postmenopausal women (n = 229) participating in the
      Estrogen Replacement and Atherosclerosis trial. Usual fiber intake was estimated
      at baseline using a food frequency questionnaire. Quantitative coronary
      angiography was performed at baseline and after 3.2 +/- 0.6 (mean +/- SD) years
      to assess changes in mean minimum coronary artery diameter and mean percent
      stenosis. RESULTS: Compared to lower intakes, > 3 g/4184 kJ (1000 kcal) of cereal
      fiber or > 6 servings of whole grains per week were associated with smaller
      decline in minimum coronary artery diameter (cereal fiber: -0.09 +/- 0.02 vs 
      0.04 +/- 0.02 mm, P = .03; whole grains: -0.10 +/- 0.02 vs -0.06 +/- 0.02 mm, P =
      .04) after adjustments for age, cardiovascular risk factors, and dietary intakes
      of saturated and polyunsaturated fat, cholesterol, and alcohol. Progression in
      percent stenosis tended to be less in women with higher intake of cereal fiber (P
      = .10) or whole-grain foods (P = .09), after similar adjustments. Intakes of
      total, fruit, and vegetable fiber, and number of servings of refined grain,
      fruits, or vegetable were not associated with progression. CONCLUSIONS: Higher
      intakes of cereal fiber and whole-grain products are associated with less
      progression of coronary atherosclerosis in postmenopausal women with established
      CAD.

PMID- 16084155
TI  - Distal embolization during primary angioplasty: histopathologic features and
      predictability.
AB  - BACKGROUND: Distal embolization during primary percutaneous coronary
      interventions (PCIs) may affect myocardial reperfusion. We evaluated the
      prevalence and features of embolization during primary PCI and its relationship
      with clinical and angiographic variables. METHODS: Forty-six consecutive patients
      with acute myocardial infarction underwent primary PCI with a filter-based distal
      protection device. Histopathologic analysis was performed on retrieved embolic
      fragments, assessing the presence and relative amount of fibrin, necrosis, lipid
      droplets, collagen, mucopolysaccharides, and leukocytes, as well as the total
      debris volume. Such variables were related to baseline clinical and angiographic
      variables. RESULTS: Embolic material was recovered in 41 (89%) of 46 cases, with
      a mean total debris volume of 1.2 +/- 2.2 mm3. Prevalent histopathologic patterns
      were organized thrombus (47%), fresh thrombus (29%), and plaque fragments (24%).
      At multivariate analysis, none of the baseline clinical variables considered
      significantly predicted the total debris volume. Among angiographic variables,
      angiographic signs of high thrombus burden (cut-off coronary occlusion pattern or
      large intracoronary minus image) independently predicted the total debris volume
      at multivariate analysis (odds ratio 15.8, P < .005). Compared with its nonuse,
      abciximab did not affect the total number and the mean total volume of embolized
      material (15 +/- 16 vs 10 +/- 8 fragments, 1.5 +/- 2.5 vs 1.0 +/- 1.9 mm3,
      respectively, for both P > .20), or its qualitative composition. CONCLUSIONS:
      Distal embolization occurs in most patients during primary PCI and mainly
      consists of plaque fragments and partially organized thrombi, which are likely to
      be scarcely responsive to antiplatelet drugs. Baseline angiographic signs of a
      high thrombus burden are the only significant predictors of the extent of distal
      embolization.

PMID- 16084156
TI  - Inflammation, endothelial cell activation, and coronary microvascular dysfunction
      in women with chest pain and no obstructive coronary artery disease.
AB  - BACKGROUND: Coronary artery microvascular dysfunction is prevalent in women with
      chest pain in the absence of obstructive coronary artery disease (CAD) and is
      manifested by attenuated coronary flow reserve (CFR). Markers of inflammation and
      endothelial cell activation have been found to be elevated in patients with chest
      pain but without CAD. The relationship between inflammation, endothelial
      activation, and CFR is not known. METHODS: Ninety-four women with chest pain in
      the absence of obstructive angiographic CAD underwent catheterization-based
      assessment of CFR and measurement of levels of inflammatory markers (n = 78) and
      endothelial cell activation in the NHLBI WISE study. RESULTS: Coronary flow
      reserve did not correlate with levels of C-reactive protein (high-sensitivity C
      reactive protein) (rs = -0.07, P = .53), interleukin (IL)-6 (rs = -0.12, P =
      .31), IL-18 (rs = 0.14, P = .23), tumor necrosis factor alpha (rs = -0.09, P =
      .43), transforming growth factor beta1 (rs = 0.02, P = .84), and soluble
      intracellular adhesion molecule-1 (rs = 0.04, P = .68). Median levels of markers
      of inflammation and endothelial cell activation did not differ between the 57
      women with abnormal CFR (< 2.5) and the 37 women with normal coronary
      microvascular function (high-sensitivity C-reactive protein 0.32 vs 0.25 mg/dL, P
      = .80; IL-6 2.89 vs 2.39 pg/mL, P = .63; IL-18 218 vs 227 pg/mL, P = .59; tumor
      necrosis factor alpha 2.7 vs 2.4 pg/mL, P = .43; transforming growth factor beta1
      9928 vs 12436 pg/mL, P = .76; soluble intracellular adhesion molecule-1 286 vs
      287 pg/mL, P = .95). Multivariable models demonstrated no evidence of
      associations between markers of inflammation and of endothelial cell activation
      and CFR. CONCLUSIONS: Coronary microvascular dysfunction is not associated with
      markers of inflammation and endothelial cell activation in women with chest pain
      in the absence of obstructive CAD. These results suggest that inflammation and
      endothelial cell activation may not play a pathophysiological role in coronary
      microvascular dysfunction.

PMID- 16084157
TI  - Facilitated percutaneous coronary intervention for acute ST-segment elevation
      myocardial infarction: results from the prematurely terminated ADdressing the
      Value of facilitated ANgioplasty after Combination therapy or Eptifibatide
      monotherapy in acute Myocardial Infarction (ADVANCE MI) trial.
AB  - BACKGROUND: Facilitated percutaneous coronary intervention (PCI)--simultaneous
      administration of glycoprotein IIb/IIIa inhibitors and reduced-dose fibrinolytics
      before primary PCI for ST-segment elevation myocardial infarction (STEMI)--may be
      a promising reperfusion strategy. METHODS: The ADVANCE MI trial was intended to
      evaluate facilitated PCI in 5640 STEMI patients but was prematurely terminated as
      a result of slow recruitment over 12 months at 30 centers in the United States.
      Patients with STEMI with planned primary PCI were randomly assigned to receive
      eptifibatide + 50% of standard-dose tenecteplase (which equated to 0.25 mg/kg
      intravenous bolus) or eptifibatide + placebo before PCI and randomized in a 2 x 2
      factorial design to unfractionated heparin or enoxaparin. RESULTS: A total of 148
      patients were randomized (74 patients in each treatment arm) and formed the "as
      randomized" intention-to-treat population. However, only 69 patients actually
      received eptifibatide + tenecteplase, and 77 actually received eptifibatide +
      placebo (2 patients did not receive eptifibatide and 4 patients randomized to
      tenecteplase did not receive this therapy)--these 146 patients formed the "as
      treated" population. Among both populations, epicardial infarct artery patency
      and myocardial tissue perfusion on pre-PCI angiography were improved in the
      tenecteplase group, but ST-segment resolution at 60 minutes was similar. The
      frequency of the primary end point of death or new/worsening severe heart failure
      at 30 days was higher among patients treated with eptifibatide + tenecteplase in
      the "as-treated" (10% vs 3%, P = .09) and the "as-randomized" (11% vs 1%, P =
      .02) populations. Bleeding complications were 2-fold higher with eptifibatide +
      tenecteplase. Analysis of the results by treatment with unfractionated heparin
      versus enoxaparin demonstrated similar findings. CONCLUSIONS: Although definitive
      conclusions cannot be made as a result of the small sample size and premature
      study termination, facilitated PCI with eptifibatide + reduced-dose tenecteplase
      was associated with improved angiographic flow patterns, increases in adverse
      clinical outcomes, and higher bleeding rates compared with eptifibatide + placebo
      administered before primary PCI for STEMI.

PMID- 16084158
TI  - Comparison of losartan and captopril on heart failure-related outcomes and
      symptoms from the losartan heart failure survival study (ELITE II).
AB  - BACKGROUND: Blockade of the renin-angiotensin system with angiotensin-converting
      enzyme inhibitors improves outcomes and symptoms in patients with heart failure
      (HF). We compared effects of losartan to captopril on mortality, morbidity, and
      functional status for patients in the ELITE II study. METHODS AND RESULTS: A
      total of 3152 patients, aged 60 years or older, with New York Heart Association
      (NYHA) classes II to IV HF and ejection fraction < or = 40% were assigned to
      receive losartan 50 mg once daily or captopril 50 mg 3 times daily. Outcome
      measures included all-cause and HF-related mortality, hospitalizations, and
      discontinuations; change in NYHA class; and quality of life (QoL). HF-related
      outcomes were not significantly different between therapies. Similar improvements
      from baseline (P < .01) in NYHA class were observed within both treatment groups.
      Among 1856 QoL participants, 1343 patients survived at least 1 year; the QoL for
      1-year survivors improved in both treatment groups (P < .001 vs baseline) and did
      not differ between groups. CONCLUSIONS: In ELITE II, the effects of losartan on
      HF-related outcomes, NYHA class, and QoL were not superior to those of captopril.
      Although angiotensin-converting enzyme inhibitors remain the treatment of choice
      for patients with HF, the similarity of the findings in the present analysis
      supports a role for angiotensin-receptor antagonists in this patient population.

PMID- 16084159
TI  - Depressive symptoms and inflammation among heart failure patients.
AB  - BACKGROUND: Psychological depression has been linked to heart failure, both an
      antecedent to and as a risk factor for poor outcomes among patients with existing
      heart failure. Elevated levels of proinflammatory cytokines have been proposed as
      a possible physiological link between the 2 conditions. The objective of this
      study was to examine the proinflammatory cytokines interleukin (IL)-6, IL-1beta,
      and tumor necrosis factor-alpha (TNFalpha) in heart failure patients with and
      without elevated symptoms of depression. METHODS: Thirty-two heart failure
      patients were recruited from an outpatient heart failure clinic. Depressive
      symptoms were measured with the Beck Depression Inventory (BDI), and a patient
      was classified as having elevated symptoms of depression if he/she scored > or =
      10. The cognitive-affective subscale score of the BDI, which measures depressed
      mood independent of physical symptoms, was also examined. RESULTS: In the
      multiple linear regression models controlling for age, sex, smoking, and
      antidepressant medication use, there was no relation between BDI score and IL-6
      (P = .7612) or IL-1beta (P = .8261). However, there was a statistically
      significant positive relation between BDI score and TNFalpha (P = .0374). There
      was also a significant relation between an elevated cognitive-affective score and
      TNFalpha (P = .0322) but no association with IL-6 (P = .8593) or IL-1beta (P =
      .3737). CONCLUSIONS: The association between TNFalpha and the cognitive-affective
      subscale, which eliminates the physical signs and symptoms that are shared by
      depression and heart failure, demonstrates a depression-specific activation of
      proinflammatory cytokines that may promote disease progression and mortality in
      patients with heart failure.

PMID- 16084160
TI  - Prognostic significance of circulating levels of angiogenic cytokines in patients
      with congestive heart failure.
AB  - BACKGROUND: Recent experimental studies have suggested that the angiogenic
      cytokines hepatocyte growth factor (HGF) and vascular endothelial growth factor
      (VEGF) may play a role in the pathogenesis of congestive heart failure (CHF). The
      aim of the present study was to test the hypothesis that HGF and VEGF
      concentrations may vary according to the different markers of CHF severity and to
      analyze the impact of HGF and VEGF concentrations on the cardiovascular mortality
      of patients with CHF. METHODS: We studied 529 consecutive patients who were
      referred to our center for an evaluation of left ventricular dysfunction.
      Hepatocyte growth factor and vascular endothelial growth factor levels were
      determined on blood samples obtained on entry into the study. Clinical follow-up
      (median 988 days) was obtained for 528 patients. RESULTS: Hepatocyte growth
      factor concentrations were strongly associated with age, diabetes mellitus, and
      all markers of CHF severity; by contrast, baseline characteristics did not differ
      among VEGF tertiles. Cardiovascular survival rates at 1, 2, and 3 years were 91%,
      87%, and 80%, respectively. The survival curves indicated a worse outcome for
      patients with high HGF concentrations at baseline (P < .0001); by contrast,
      cardiovascular survival was similar across the tertiles of VEGF (P = .37).
      Hepatocyte growth factor concentrations were higher in the 109 patients with a
      cardiovascular event (1001 [741-1327] pg/mL) than in the 419 patients without
      (773 [610-1045] pg/mL, P < .0001). By multivariate analysis, a baseline HGF
      concentration >802 pg/mL was associated with an increased cardiovascular
      mortality (hazard ratio = 1.85, 95% CI 1.09-3.13, P = .02); other variables
      retained into the final model were B-type natriuretic peptide (P < .0001), peak
      oxygen consumption (P = .0002), and ischemic etiology (P = .0005). CONCLUSIONS:
      Hepatocyte growth factor levels correlate with CHF severity and are associated
      with an increased cardiovascular mortality during follow-up.

PMID- 16084161
TI  - Relationships among exercise capacity, hypertrophy, and left ventricular
      diastolic function in nonobstructive hypertrophic cardiomyopathy.
AB  - AIM: The aim of this study was to analyze the relationships among exercise
      capacity (EC), hypertrophy, and diastolic function in nonobstructive hypertrophic
      cardiomyopathy (NOHCM). METHODS AND RESULTS: Twenty-seven patients with NOHCM
      were studied. Left ventricular hypertrophy (LVH) was determined by appropriate
      echocardiographic indexes. For diastolic function evaluation, the following were
      measured: the early (E) and late (A) waves, E/A, and deceleration time of E of
      the mitral flow; the systolic (S), diastolic (D), and atrial reversal (AR) waves,
      S/D, and the atrial systolic filling fraction of the pulmonary vein flow; and the
      early (Ea), late (Aa) waves, Ea/Aa, and E/Ea by tissue Doppler imaging. The
      difference between the duration of AR and A waves (DurAR - DurA), the peak VO2,
      and anaerobic threshold (AT) were also determined. In these patients, the E/Ea
      ratio was 8.9 +/- 3.2 and DurAR - DurA was 22.6 +/- 32.6 milliseconds. The peak
      VO2 and AT correlated with D (r = 0.55, P = .003 and .51, P = .007, respectively)
      and Ea/Aa (r = 0.56, P = .007 and .45, P = .03, respectively). There was no
      correlation between EC and LVH. CONCLUSIONS: Patients with NOHCM demonstrated
      evidences of elevated left ventricular (LV) end-diastolic pressure with normal
      filling pressure. EC compromise may be attributed to relaxation changes with
      inadequate filling of the left ventricle.

PMID- 16084162
TI  - Randomized comparison of anterolateral versus anteroposterior electrode position
      for biphasic external cardioversion of atrial fibrillation.
AB  - BACKGROUND: In biphasic external cardioversion (CV) of atrial fibrillation (AF),
      the influence of different electrode positions on efficacy and incidence of early
      recurrent atrial fibrillation is not known. This study compared anteroposterior
      (AP) vs anterolateral (AL) electrode positioning. METHODS: Consecutive patients
      referred for CV of persistent AF were randomized either to an AP or an AL
      electrode position. Biphasic external CV was performed with standardized
      electrode positions and rising energy delivery. RESULTS: Both groups (N = 123,
      mean age 66 years, 71% male, 83% with structural cardiovascular disease or
      hypertension) did not differ concerning age, sex, body mass index, chronic
      antiarrhythmic therapy, duration of AF, left ventricular ejection fraction, and
      left atrial diameter. Cumulative success rates were comparable (AP 94.9% vs AL
      95.2%, P = ns). First-shock efficacy did not differ (AP 78.3% vs AL 74.6%, P =
      ns). Early recurrent atrial fibrillation (AF relapse < 1 minute after successful
      CV) occurred in 8.1% (AP 11.6% vs AL 4.8%, P = ns). Mean number of shocks was 1.3
      per patient with the AP configuration and 1.4 per patient with the AL
      configuration (P = ns). Mean cumulative energy delivery was also comparable (AP
      171 WS vs AL 198 WS, P = ns). CONCLUSIONS: Both electrode positions are similar
      in biphasic external CV of AF with regard to acute success and early recurrent
      atrial fibrillation. Also, the number of shocks needed and energy delivery are
      comparable with both electrode configurations.

PMID- 16084163
TI  - Depressed autonomic nervous system function in African Americans and individuals
      of lower social class: a potential mechanism of race- and class-related
      disparities in health outcomes.
AB  - BACKGROUND: Both race and social class influence cardiovascular outcomes, through
      mechanisms not yet fully understood. Minority race and lower social class are
      sources of chronic stress, which can alter autonomic nervous system function.
      Heart rate variability (HRV), a measure of autonomic function, is also an
      important predictor of cardiovascular outcomes. METHODS: To determine whether
      minority race/ethnicity and lower social class are associated with depressed HRV,
      we prospectively collected data on sociodemographic, clinical, psychological, and
      behavioral factors by survey in 360 outpatients undergoing ambulatory
      electrocardiographic monitoring. Heart rate variability (24-hour) was measured by
      frequency domain analysis. RESULTS: In unadjusted analysis, African Americans had
      lower HRV than whites, and individuals of lower social class as measured by
      education, occupation, and income had lower HRV than those of higher class. In
      multivariable analysis, both race and social class were independent predictors of
      ultralow frequency power after controlling for clinical and psychological
      factors. African Americans were 3.45 (95% CI 1.74-6.98, P = .0004) times as
      likely as whites to have depressed HRV (ultralow frequency power, lowest
      tertile), and non-college graduates 2.94 (95% CI, 1.71-5.14, P = .0001) times as
      likely as college graduates to have depressed HRV. CONCLUSIONS: Heart rate
      variability is lower in African Americans and individuals of lower social class,
      independent of the effects of measured clinical, psychological, or behavioral
      factors. This suggests that the adverse effects of minority race and lower social
      class on cardiovascular outcomes may be mediated by dysregulation of autonomic
      function.

PMID- 16084164
TI  - Prognostic value of electrocardiographic criteria for left ventricular
      hypertrophy.
AB  - BACKGROUND: Many electrocardiographic (ECG) criteria for left ventricular
      hypertrophy (LVH) exist, but few studies have compared their relative prognostic
      value for predicting cardiovascular (CV) mortality. METHODS: We analyzed the
      first ECG on 46950 consecutive veterans. We targeted male outpatients with a body
      mass index > 20 to avoid confounding by complicating catabolic illnesses and
      further excluded those with conduction abnormalities. Using Cox regression models
      adjusted for age, heart rate, and body mass index, we compared the hazard ratios
      (HRs) for CV mortality obtained from seventeen commonly used ECG criteria for
      LVH. RESULTS: During a mean follow-up of 7 +/- 4 years, in a total population of
      19434 patients (mean age 54 +/- 14 years), 1254 (6%) patients died of CV causes.
      The adjusted HR for CV mortality ranged from 1.4 (95% CI 1.2-1.6) to 3.7 (95% CI
      2.7-5.0) among the various criteria. Left ventricular hypertrophy defined by
      composite criteria was generally associated with higher adjusted HRs compared
      with voltage-only criteria. Among patients with ECG-LVH, the presence of a left
      ventricular strain pattern or increased negative P-terminal force were most
      predictive of CV mortality (HR 3.9 and 3.5, 95% CI 3.3-4.6 and 2.8-4.2).
      CONCLUSIONS: Compared with voltage-only criteria for detecting LVH, composite ECG
      criteria are more strongly predictive of CV mortality. By applying these ECG
      criteria into routine clinical practice, individuals with LVH who are at higher
      risk for CV mortality can be identified and appropriately treated.

PMID- 16084165
TI  - Left ventricular diastolic function in normotensive subjects 2 months after acute
      myocardial infarction is related to glucose intolerance.
AB  - BACKGROUND: Both glucose intolerance and myocardial infarction are independently
      associated with impaired left ventricular (LV) function. This study was carried
      out to relate LV diastolic function in normotensive subjects 2 months after acute
      myocardial infarction (AMI) to glucose tolerance status. METHODS: Left
      ventricular ejection fraction (LVEF), LV mass index, peak velocity of the early
      phase/atrial contraction wave, deceleration time of E wave, and isovolumic
      relaxation time were measured during echocardiograph/Doppler cardiography in 200
      normotensive patients 2 months after AMI. Twenty-nine patients were known to be
      diabetic on admission with AMI. Glucose tolerance test was carried out in the 171
      patients who are not known to be diabetic. RESULTS: Independent of LVEF,
      restrictive LV filling (peak velocity of the early phase/atrial contraction wave
      > 1 but < 2 associated with deceleration time of E wave < or = 140 milliseconds)
      was found in 72% of the known-diabetic patients, 70% of the 20 preclinical
      diabetic patients, 23% of the 35 patients with impaired glucose tolerance, 13% of
      the 15 patients with stress hyperglycemia, and 7% of the euglycemic patients (P <
      .01). In the rest of these patients, LV filling was nonrestrictive. No
      significant difference was observed in LVEF and LV mass index between patient
      groups. CONCLUSION: Independent of LVEF, the pattern of abnormal LV filling in
      normotensive subjects 2 months after AMI is a function of the severity of glucose
      intolerance, restrictive in the majority of the diabetic patients and
      nonrestrictive in the majority of the euglycemic patients, impaired glucose
      tolerance, and stress hyperglycemia. After AMI, abnormal LV filling occurs even
      in the absence of detectable systolic dysfunction or left ventricular
      hypertrophy.

PMID- 16084166
TI  - The impact of acute coronary syndrome on clinical, economic, and cardiac-specific
      health status after coronary artery bypass surgery versus stent-assisted
      percutaneous coronary intervention: 1-year results from the stent or surgery
      (SoS) trial.
AB  - BACKGROUND: Data are limited regarding the impact of acute coronary syndromes
      (ACSs) on the relative benefits of coronary artery bypass grafting (CABG) versus
      stent-assisted percutaneous coronary intervention (PCI). METHODS: The SoS trial
      compared patients with multivessel disease who were randomly assigned to CABG (n
      = 500) or stent-assisted PCI (n = 488). The impact of treatment on 1-year
      outcomes was compared in ACS (n = 126, CABG; n = 116, PCI) and non-ACS (n = 374,
      CABG; n = 372, PCI) subgroups. RESULTS: Baseline characteristics were similar
      between treatment groups within ACS and non-ACS groups, as was the 1-year
      composite incidence of mortality and myocardial infarction (ACS, 5.2% for PCI vs
      5.6% for CABG, P = .89; non-ACS, 7.0% vs 8.3%, P = .50). The need for repeat
      revascularizations was higher after PCI versus CABG within each subgroup (ACS,
      15.5% vs 7.1%, P = .04; non-ACS, 18.0% vs 3.2%, P < .001). At 6 and 12 months,
      scores on the Seattle Angina Questionnaire improved significantly in patients
      with and without ACS. In patients without ACS, CABG was associated with greater
      improvement in physical limitation, angina frequency, and quality of life at 6
      and 12 months. In patients with ACS, there was only a nonsignificant slight trend
      toward greater improvement with CABG at 1 year. The total 1-year costs for PCI
      and CABG in patients without ACS were 5760 pound sterling and 8509 pound sterling
      (Delta = 2749 pound sterling, 95% CI 1890 pound sterling - 3409 pound sterling),
      and in patients with ACS, 8014 pound sterling and 10080 pound sterling (Delta =
      2066 pound sterling, 95% CI -690 pound sterling to 3487 pound sterling).
      CONCLUSIONS: In patients with and without ACS, CABG had similar clinical
      outcomes, less need for repeat revascularization and higher costs compared to
      PCI. The benefit of CABG relative to PCI in improving patients' health status
      tended to be greater in patients without ACS than in patients with ACS.

PMID- 16084167
TI  - Improved long-term survival associated with stent deployment during percutaneous
      coronary interventions: results from a registry of 3399 patients.
AB  - INTRODUCTION: The use of stents in percutaneous coronary intervention (PCI)
      improves procedural success and reduces restenosis. However, few studies have had
      a sufficient sample size or adequate follow-up to determine whether this
      advantage results in a positive effect on mortality. METHODS: A total of 3399
      patients undergoing PCI (stented [with dual antiplatelet therapy]: n = 2456,
      nonstented [balloon PCI or rotational atherectomy]: n = 942) at a single
      institution from 1994 to 2001 were followed up prospectively (43 +/- 22 and 54 +/
      25 months, respectively) for acute and long-term clinical outcomes. RESULTS:
      Angiographic success (< 50% residual stenosis) (99.7% vs 97.7%, P < .001) and
      acute gain (3.02 +/- 0.55 vs 2.08 +/- 0.62 mm, P < .001) were both greater for
      stented lesions. Likewise, procedural complications of death (0.04% vs 0.4%, P =
      .02) and dissection (4.9% vs 8.0%, P = .001) were lower in the stent group, as
      were rates of 6-month clinical restenosis (10.3% vs 16.3%, P < .001). Eight-year
      mortality (12.0% vs 18.2%, hazard ratio = 0.78, P = .009) was lower among the
      stent group, as was long-term major adverse cardiac events (36.2% vs 50.6%, P <
      .001), but no difference in long-term myocardial infarction was found (6.5% vs
      7.6%, P = .28). In multivariable Cox regression, stent use (hazard ratio = 0.76,
      95% CI [0.58-0.99], P = .04) remained associated with significantly reduced
      mortality. CONCLUSION: This large prospective study demonstrates that, in
      addition to a general improvement in procedural success and a reduced need for
      repeat revascularization, the use of stents with dual antiplatelet therapy was
      associated with a significant reduction in long-term mortality. Consideration
      should be given for the use of stents whenever feasible during PCI.

PMID- 16084168
TI  - Science, skepticism, and global warming.

PMID- 16084169
TI  - Treatment of hepatitis C.
AB  - Hepatitis C virus is a leading cause of chronic liver disease, with over 170
      million people infected worldwide. It is also the leading indication for liver
      transplantation. Complications from chronic hepatitis C infection include
      cirrhosis, hepatic decompensation, and hepatocellular carcinoma. As a result,
      treatment strategies to prevent such complications have been widely researched,
      although many questions remain unanswered. To date, the standard therapy for
      chronic hepatitis C infection is the combination of peginterferon and ribavirin.
      Treatment strategies differ based on factors such as genotype and liver biopsy
      results. Other strategies must be considered for special groups, such as patients
      with acute hepatitis C infection, hepatitis C/human immunodeficiency virus (HIV)
      coinfection, and prior nonresponse to interferon or relapse after its use. The
      goal of therapy is to achieve a sustained virologic response (ie, no detectable
      hepatitis C ribonucleic acid 6 months after completion of therapy). The
      substantial adverse effects associated with both interferon alfa and ribavirin
      often make it difficult for patients to continue with their therapies.

PMID- 16084170
TI  - Serum uric acid and cardiovascular disease: recent developments, and where do
      they leave us?
AB  - The relationship between serum uric acid (SUA) and cardiovascular disease has
      been controversial. Here we review recent literature assessing whether
      hyperuricemia is an independent risk factor for adverse cardiovascular outcomes.
      Studies from the past 6 years evaluating the association of SUA with
      cardiovascular disease were identified through MEDLINE, EMBASE, and Cochrane
      library searches, bibliography cross-referencing, and review articles. Twenty-one
      cohort studies in healthy and high-risk patients with cardiovascular disease were
      identified and reviewed. In studies of high-risk patients, in which more overall
      events were recorded, 10 of 11 studies were supportive of an independent
      association. In 10 studies of healthy patients, 6 suggested an independent
      association of SUA with adverse cardiovascular outcomes. Increasing SUA is likely
      an independent risk factor for cardiovascular disease in high-risk individuals.
      However, the magnitude of excess risk attributable to high SUA is likely to be
      small in healthy individuals. Trials of SUA-lowering therapy in hyperuricemic
      patients evaluating the effect on cardiovascular outcomes are justified in high
      risk patients.

PMID- 16084171
TI  - Has mortality from acute renal failure decreased? A systematic review of the
      literature.
AB  - PURPOSE: To determine mortality rates in patients with acute renal failure during
      the past decades. METHODS: We performed a MEDLINE search using the keywords
      "acute renal failure" crossed with "outcome," "mortality," "ICU," "critically
      ill" or "prognosis" in the period from January 1970 to December 2004. Abstracts
      and full articles were eligible if mortality rates were reported. We also
      reviewed the bibliographies of available studies for further potentially eligible
      studies. The dates of the observation period for each study and not the
      publication dates were considered for the analysis, so the earliest data were
      from 1956. RESULTS: Of 85 articles fulfilling the criteria, 5 were excluded
      because of duplicate publications using the same database, so that 80 were
      included in our review with a total of 15897 patients. Mortality rates in most
      studies exceeded 30%, and there was no consistent change over time. CONCLUSION:
      Despite technical progress in the management of acute renal failure over the last
      50 years, mortality rates seem to have remained unchanged at around 50%.

PMID- 16084172
TI  - A much-delayed complication.

PMID- 16084173
TI  - Midbrain infarction presenting isolated medial rectus nuclear palsy.

PMID- 16084174
TI  - What is the real rhythm?

PMID- 16084175
TI  - Time tells the tale.

PMID- 16084176
TI  - Statin therapy reduces contrast-induced nephropathy: an analysis of contemporary
      percutaneous interventions.
AB  - PURPOSE: We sought to examine whether statin therapy before percutaneous coronary
      intervention results in reduction in contrast-induced nephropathy (CIN).
      Intravascular administration of contrast media can have nephrotoxic effects,
      particularly in patients with baseline renal insufficiency. Along with lowering
      serum cholesterol, statins have pleiotropic effects in the vasculature. The
      effect of statin use on CIN is unknown. SUBJECTS AND METHODS: We studied 29409
      patients who had both baseline preprocedure and peak postprocedure serum
      creatinine measured at the time of their percutaneous coronary intervention
      (PCI). Baseline demographics and creatinine profile before and after the
      procedure were compared between patients who received preprocedure statins and
      those who did not. CIN was defined as an increase in serum creatinine of < or
      =0.5 mg/dL. RESULTS: Baseline serum creatinine was similar between the two
      groups. When compared with patients who did not receive preprocedure statins,
      patients on preprocedure statins had a lower incidence of CIN (4.37 vs 5.93, P
      <0.0001) and nephropathy requiring dialysis (0.32 vs 0.49, P = 0.03). After
      adjustments for comorbidities, preprocedure statin use was associated with a
      significant reduction in CIN (odds ration [OR] 0.87, 95% confidence interval [CI]
      0.77-0.99, P = 0.03). CONCLUSIONS: Preprocedure statin use is associated with
      significant reduction in CIN after contemporary PCI. This reinforces the need to
      initiate statin therapy before percutaneous coronary interventions.

PMID- 16084177
TI  - Lifetime implications and cost-effectiveness of using finasteride to prevent
      prostate cancer.
AB  - PURPOSE: We estimate the lifetime implications of daily treatment with
      finasteride following the results of the Prostate Cancer Prevention Trial (PCPT).
      In this trial, prostate cancer prevalence was reduced by 25%; however, an
      increase in the number of high-grade tumors among the treatment group
      necessitates the long-term projection of the likely benefits and costs. METHODS:
      We use a Markov decision analysis model with data from the trial, the SEER
      program, and published literature. The model measures the cost per life-year and
      cost per quality-adjusted life-year (QALY) gained for a cohort of men age 55
      years who initiate preventive treatment with finasteride. RESULTS: Finasteride is
      associated with a gain of 6 life-years per 1000 men treated at an incremental
      cost of 1660000 dollars per life-year gained. The quality-adjusted analysis
      results in 46 QALYs gained per 1000 men treated at an incremental cost of 200000
      dollars per QALY gained, due primarily to the favorable effects of finasteride on
      benign prostatic hyperplasia. Under the assumption that the increase in high
      grade tumors observed among finasteride treated men is a pathologic artifact, the
      incremental costs are 290000 dollars per life-year gained and 130000 dollars per
      QALY gained. CONCLUSIONS: The cost burden associated with finasteride is
      substantial, while its survival benefit is small and only realized many years
      after initiating treatment. To achieve an incremental cost below 100000 dollars
      per QALY gained, the price of finasteride must be reduced by 50% from its current
      average wholesale price and finasteride must be shown to prevent high-grade as
      well as low-grade disease.

PMID- 16084178
TI  - Medication performance measures and mortality following acute coronary syndromes.
AB  - PURPOSE: To identify patient and health care factors which are related to the use
      of medical treatments that comprise quality measures and to assess the relation
      of these measures with mortality. METHODS: The study sample consisted of 20 140
      patients with acute coronary syndromes from the international GRACE registry.
      Multivariable logistic regression modeling was used to determine predictors of
      quality performance. Quality indicators were use of aspirin and beta-blockers
      within 24 hours and at hospital discharge, use of angiotensin-converting enzyme
      (ACE) inhibitors at discharge, and in-hospital mortality. RESULTS: Use of
      medications in eligible patients at discharge ranged from 73% for ACE inhibitors
      to 93% for aspirin. High-risk features (eg, heart failure, older age) were
      related to failure to use aspirin and beta-blockers. Being at a teaching hospital
      and care by a cardiologist were associated with better use of aspirin and beta
      blockers. Coronary artery bypass surgery was associated with failure to use ACE
      inhibitors and aspirin. When hospitals were divided into quartiles of quality
      performance, adjusted in-hospital mortality was 4.1% in the top versus 5.6% in
      the bottom quartile, representing a 27% (95% confidence interval: 11% to 42%)
      lower relative mortality. CONCLUSION: Identification of factors associated with
      failure to use proven treatments, including high-risk groups that would derive
      particular benefit from effective therapies, provides an opportunity to focus
      quality improvement interventions. The association of lower hospital mortality
      with better use of selected medical treatments supports their measurement to
      improve quality of care.

PMID- 16084179
TI  - A simple clinical score accurately predicts outcome in a community-based
      population undergoing stress testing.
AB  - PURPOSE: Scoring systems based on clinical variables are available but not widely
      applied for evaluating patients with chronic coronary artery disease. The purpose
      of this study was to validate the prognostic value of a simple clinical scoring
      system, originally developed in patients referred for a nuclear stress test at a
      tertiary-care medical center, in a less-selected, community-based population
      undergoing stress testing for known or suspected coronary artery disease.
      SUBJECTS AND METHODS: Over a 4-year period, 3546 residents of Olmsted County,
      Minn, underwent stress testing. A previously developed clinical score was
      calculated for every patient by assigning 1 point each for: male sex, history of
      myocardial infarction, typical angina, diabetes, insulin use, and each decade of
      age beginning at age 40. The associations between the assigned score and clinical
      endpoints were tested using logistic regression. A previously established cutoff
      point of 5 was used to establish risk groups. RESULTS: During follow-up (7.6 +/-
      2.7 years) there were 363 total deaths, 109 cardiac deaths, and 132 nonfatal
      myocardial infarctions. The clinical score was strongly associated with overall
      mortality, cardiac death, and cardiac death/myocardial infarction (P <0.001 for
      all 3 endpoints). Annual mortality was .6% for the 3076 patients (86%) with a
      score < or =4, 2.4% for 275 patients (8%) with a score = 5 and 6.2% for the 215
      patients (6%) with a score > or =6. CONCLUSIONS: This study enhances the
      generalizability of this simple clinical score, which was highly effective for
      risk-stratifying this community-based population undergoing evaluation of chronic
      coronary artery disease.

PMID- 16084180
TI  - Competency in electrocardiogram interpretation among internal medicine and
      emergency medicine residents.
AB  - PURPOSE: Accurate interpretation of the electrocardiogram is critical, yet there
      are no evidence-based guidelines for assessing competency. Our study evaluated
      the ability of internal medicine residents and emergency medicine residents to
      interpret a variety of electrocardiograms. METHODS: The 120 participants included
      87 internal medicine residents and 33 emergency medicine residents at two
      hospitals. Participants reported their sex, training level, adequacy of training,
      career interest in cardiology, and estimated electrocardiogram proficiency. They
      then took a test containing 12 electrocardiograms and recorded their diagnosis
      and certainty. Two cardiologists independently established the correct diagnoses.
      Two blinded, independent graders scored each electrocardiogram (0 = incorrect, 1
      = partially correct, 2 = correct). RESULTS: The median proficiency was 6 out of
      10, total electrocardiogram score was 15 of 24, and certainty was 33 of 48. There
      was no significant difference in overall competency between emergency medicine
      and internal medicine residents (14.0 vs 15.0, P = 0.239). Internal medicine
      residents interested in a cardiology career scored higher than those not
      interested in a cardiology career (17.3 vs. 14.1, P = 0.003). When analyzing the
      most critical diagnoses, we found that the mean score for ventricular tachycardia
      was 1.6 of 2.0, for myocardial infarction was 1.3 of 2.0, and for complete heart
      block was 0.8 of 2.0. Over half of the participants felt their electrocardiogram
      training was inadequate. CONCLUSION: Despite improvement in interpretation with
      clinical experience, overall performance was low. Research is needed to find
      optimal methods to improve electrocardiogram competency.

PMID- 16084181
TI  - Do drug samples influence resident prescribing behavior? A randomized trial.
AB  - PURPOSE: The purpose of the study was to determine whether access to drug samples
      influences resident prescribing decisions. SUBJECTS AND METHODS: The authors
      observed 390 decisions to initiate drug therapy by 29 internal medicine residents
      over a 6-month period in an inner-city primary care clinic. By random selection,
      half of the residents agreed not to use available free drug samples. Five drug
      class pairs were chosen for study prospectively. Highly advertised drugs were
      matched with drugs commonly used for the same indication that were less
      expensive, available over-the-counter, or available in generic formulation.
      RESULTS: Resident physicians with access to drug samples were less likely to
      choose unadvertised drugs (131/202 decisions) than residents who did not have
      access to samples (138/188 decisions; P = .04) and less likely to choose over-the
      counter drugs (51/202, 73/188; P = .003). There was a trend toward less use of
      inexpensive drugs. CONCLUSION: Access to drug samples in clinic influences
      resident prescribing decisions. This could affect resident education and increase
      drug costs for patients.

PMID- 16084182
TI  - Eliminating analgesic meperidine use with a supported formulary restriction.
AB  - PURPOSE: Meperidine is a commonly used analgesic despite unique disadvantages
      compared with other opioid analgesics. The objective of this study was to measure
      the effects of a meperidine formulary restriction on the prescribing of
      parenteral opioid analgesics. MATERIALS AND METHODS: The study was performed at a
      single 750-bed tertiary care teaching hospital in Rochester, NY. The formulary
      restriction limited meperidine to use exclusively for rigors or procedural
      sedation and was supported by an educational initiative and a computerized order
      entry system. Independent computerized pharmacy records were used to capture all
      doses of parenteral morphine, meperidine, and hydromorphone administered to
      patients in the emergency department or on a medical or surgical inpatient floor
      during data-collection periods. Baseline data were collected during two 3-day
      periods before the formulary restriction; then comparison data were collected
      during three 3-day periods over 15 months after the formulary restriction.
      RESULTS: The number of administered doses of meperidine per day decreased from
      37.5 (20.8% of parenteral opioid doses before the restriction) to 0.22 (0.1% of
      parenteral opioid doses, P = .001). The total number of opioid doses and morphine
      doses given did not change, whereas the number of hydromorphone doses increased
      significantly postrestriction, from 16.0 doses per day (8.9% of total) to 59.7
      doses per day (29.5%) (P = .009). CONCLUSION: Meperidine formulary restriction,
      supported by an educational program and computerized order entry, effectively
      eliminated analgesic meperidine use. Hydromorphone use increased proportionately
      to offset the decreased use of meperidine.

PMID- 16084183
TI  - Estimating the proportion of patients infected with HIV who will die of comorbid
      diseases.
AB  - PURPOSE: Effective antiretroviral therapies have improved the prognosis for
      patients infected with the human immunodeficiency virus (HIV). We aimed to
      estimate the likelihood that HIV-infected patients would die of comorbid disease.
      METHODS: A probabilistic simulation of antiretroviral-naive HIV-infected patients
      in the United States was calibrated with data from an observational cohort (N =
      3545) and validated with data from a separate patient cohort (N = 12574). The
      simulation explicitly represents the 2 main determinants of treatment failure and
      subsequent death from HIV-related causes: nonadherence to combination therapy and
      accumulation of phenotypic resistance to combination therapy. The likelihood of
      deaths not directly attributable to HIV was estimated from the Collaborations in
      HIV Outcomes Research-US (CHORUS) cohort. RESULTS: For patients with newly
      diagnosed HIV infections, CD4 counts of 500 cells/mm3, and viral loads of 10000
      copies/mL, the median estimated survival was 26.8 years for 30-year-olds, 24.4
      years for 40-year-olds and 14.6 years for 50-year-olds. The proportion of deaths
      not directly attributable to HIV was 36% for 30-year-olds, 53% for 40-year-olds,
      and 72% for 50-year-olds. For patients with characteristics similar to CHORUS
      participants, the median estimated survival approached 20.4 years, the mean age
      at death approached 60.4 years, and 41% died of illnesses not directly
      attributable to HIV. These estimates of non-HIV mortality were likely
      conservative. CONCLUSION: As HIV-infected patients live longer, our results
      suggest they will experience increasing mortality from causes not directly
      attributable to HIV. The projected risk from comorbid disease has clinical and
      policy implications for future delivery of care to HIV-infected patients.

PMID- 16084184
TI  - Male microchimerism in women without sons: quantitative assessment and
      correlation with pregnancy history.
AB  - PURPOSE: Fetal microchimerism, derived from fetal cells that persist after
      pregnancy, is usually evaluated by tests for male microchimerism in women who
      gave birth to sons. We investigated male microchimerism in women without sons and
      examined correlation with prior pregnancy history. Immunologic consequences of
      microchimerism are unknown. We studied healthy women and women with rheumatoid
      arthritis (RA). METHODS: Y-chromosome-specific real-time quantitative polymerase
      chain reaction was used to test peripheral blood mononuclear cells of 120 women
      (49 healthy and 71 with RA). Results were expressed as the number of male cells
      that would be equivalent to the total amount of male DNA detected within a sample
      containing the equivalent of 100000 female cells. RESULTS: Male microchimerism
      was found in 21% of women overall. Healthy women and women with RA did not
      significantly differ (24% vs 18%). Results ranged from the DNA equivalent of 0 to
      20.7 male cells per 100000 female cells. Women were categorized into 4 groups
      according to pregnancy history. Group A had only daughters (n = 26), Group B had
      spontaneous abortions (n = 23), Group C had induced abortions (n = 23), and Group
      D were nulligravid (n = 48). Male microchimerism prevalence was significantly
      greater in Group C than other groups (8%, 22%, 57%, 10%, respectively). Levels
      were also significantly higher in the induced abortion group. CONCLUSIONS: Male
      microchimerism was not infrequent in women without sons. Besides known
      pregnancies, other possible sources of male microchimerism include unrecognized
      spontaneous abortion, vanished male twin, an older brother transferred by the
      maternal circulation, or sexual intercourse. Male microchimerism was
      significantly more frequent and levels were higher in women with induced abortion
      than in women with other pregnancy histories. Further studies are needed to
      determine specific origins of male microchimerism in women.

PMID- 16084185
TI  - Polymorphisms of endothelial nitric oxide synthase and angiotensin-converting
      enzyme in systemic sclerosis.

PMID- 16084186
TI  - Detection of left atrial enlargement using hand-carried ultrasound devices to
      screen for cardiac abnormalities.

PMID- 16084187
TI  - Primary care physicians, office-based practice, and the meaning of quality
      improvement.

PMID- 16084188
TI  - Relapsing esophageal and gastric ulcers revealing Wegener's granulomatosis.

PMID- 16084189
TI  - Multifocal septic arthritis: an unusual complication of invasive Streptococcus
      pyogenes infection.

PMID- 16084190
TI  - Impetigo-like vegetating nasal lesions caused by Klebsiella pneumoniae.

PMID- 16084191
TI  - Thyrotoxicosis and pulmonary hypertension.

PMID- 16084192
TI  - Community-acquired pneumonia guidelines and resident behavior.

PMID- 16084193
TI  - Predictors of urinary tract infection after menopause: a prospective study.

PMID- 16084195
TI  - Clinical skills training: time for a national dialogue and consensus.

PMID- 16084196
TI  - The Sheila experience.

PMID- 16084197
TI  - Abstracts from the 8th Iranian Congress of Biochemistry (ICB) and First
      International Congress of Biochemistry and Molecular Biology (ICBMB). Tehran,
      Iran. September 11-15, 2005.

PMID- 16084198
TI  - Molecular basis of the effects of shear stress on vascular endothelial cells.
AB  - Blood vessels are constantly exposed to hemodynamic forces in the form of cyclic
      stretch and shear stress due to the pulsatile nature of blood pressure and flow.
      Endothelial cells (ECs) are subjected to the shear stress resulting from blood
      flow and are able to convert mechanical stimuli into intracellular signals that
      affect cellular functions, e.g., proliferation, apoptosis, migration,
      permeability, and remodeling, as well as gene expression. The ECs use multiple
      sensing mechanisms to detect changes in mechanical forces, leading to the
      activation of signaling networks. The cytoskeleton provides a structural
      framework for the EC to transmit mechanical forces between its luminal, abluminal
      and junctional surfaces and its interior, including the cytoplasm, the nucleus,
      and focal adhesion sites. Endothelial cells also respond differently to different
      modes of shear forces, e.g., laminar, disturbed, or oscillatory flows. In vitro
      studies on cultured ECs in flow channels have been conducted to investigate the
      molecular mechanisms by which cells convert the mechanical input into biochemical
      events, which eventually lead to functional responses. The knowledge gained on
      mechano-transduction, with verifications under in vivo conditions, will advance
      our understanding of the physiological and pathological processes in vascular
      remodeling and adaptation in health and disease.

PMID- 16084199
TI  - Predicting masticatory jaw movements from chin movements using multivariate
      linear methods.
AB  - Previously, we have used bivariate correlations of maximum and minimum
      displacement, velocity and acceleration variables to compare masticatory chin and
      jaw movements (J. Prosthet. Dent. 81 (1999) 179). This previous study represented
      a first step in exploring the hypothesis that the chin contained useful
      information regarding jaw kinematics. The current study extends our understanding
      of the relationship between masticatory chin and jaw movements by: (1)
      reconstructing and evaluating a more continuous trajectory of chin and jaw
      movements, and (2) performing multivariate correlations comparing chin and jaw
      movements at discrete points along the trajectory in order to gain insight into
      the coupling of chin and jaw movements during a chewing cycle. Results indicated
      that chin and jaw movement trajectories were visually similar in the lateral,
      vertical, and anteroposterior axes. The adjusted R(2) results in the lateral,
      vertical, and anteroposterior dimensions averaged 0.74, 0.78, and 0.89,
      respectively. Within chewing cycles, the lowest correlations between chin and jaw
      movements in the lateral and vertical dimensions occurred when the jaw was
      relatively closed, whereas the lowest correlations between chin and jaw movements
      in the anteroposterior dimension occurred while the jaw was opening from a closed
      position. The results indicated that jaw and chin movements were qualitatively
      similar and that at least 74% of the variation in jaw movements could be
      accounted for by multivariate linear models of chin movement.

PMID- 16084200
TI  - Trunk stiffness and dynamics during active extension exertions.
AB  - Spinal stability is related to the recruitment and control of active muscle
      stiffness. Stochastic system identification techniques were used to calculate the
      effective stiffness and dynamics of the trunk during active trunk extension
      exertions. Twenty-one healthy adult subjects (10 males, 11 females) wore a
      harness with a cable attached to a servomotor such that isotonic flexion preloads
      of 100, 135, and 170 N were applied at the T10 level of the trunk. A pseudorandom
      stochastic force sequence (bandwidth 0-10 Hz, amplitude +/-30 N) was superimposed
      on the preload causing small amplitude trunk movements. Nonparametric impulse
      response functions of trunk dynamics were computed and revealed that the system
      exhibited underdamped second-order behavior. Second-order trunk dynamics were
      determined by calculating the best least-squares fit to the IRF. The quality of
      the model was quantified by comparing estimated and observed displacement
      variance accounted for (VAF), and quality of the second-order fits was calculated
      as a percentage and referred to as fit accuracy. Mean VAF and fit accuracy were
      87.8 +/- 4.0% and 96.0 +/- 4.3%, respectively, indicating that the model
      accurately represented active trunk kinematic response. The accuracy of the
      kinematic representation was not influenced by preload or gender. Mean effective
      stiffness was 2.78 +/- 0.96 N/mm and increased significantly with preload (p <
      0.001), but did not vary with gender (p = 0.425). Mean effective damping was 314
      +/- 72 Ns/m and effective trunk mass was 37.0 +/- 9.3 kg. We conclude that
      stochastic system identification techniques should be used to calculate effective
      trunk stiffness and dynamics.

PMID- 16084201
TI  - A transversely isotropic, transversely homogeneous microstructural-statistical
      model of articular cartilage.
AB  - Articular cartilage is a multi-phasic, composite, fibre-reinforced material.
      Therefore, its mechanical properties are determined by the tissue microstructure.
      The presence of cells (chondrocytes) and collagen fibres within the proteoglycan
      matrix influences, at a local and a global level, the material symmetries. The
      volumetric concentration and shape of chondrocytes, and the volumetric
      concentration and spatial arrangement of collagen fibres have been observed to
      change as a function of depth in articular cartilage. In particular, collagen
      fibres are perpendicular to the bone-cartilage interface in the deep zone, their
      orientation is almost random in the middle zone, and they are parallel to the
      surface in the superficial zone. The aim of this work is to develop a model of
      elastic properties of articular cartilage based on its microstructure. In
      previous work, we addressed this problem based on Piola's notation for fourth
      order tensors. Here, mathematical tools initially developed for transversely
      isotropic composite materials comprised of a statistical orientation of
      spheroidal inclusions are extended to articular cartilage, while taking into
      account the dependence of the elastic properties on cartilage depth. The
      resulting model is transversely isotropic and transversely homogeneous (TITH),
      the transverse plane being parallel to the bone-cartilage interface and the
      articular surface. Our results demonstrate that the axial elastic modulus
      decreases from the deep zone to the articular surface, a result that is in good
      agreement with experimental findings. Finite element simulations were carried
      out, in order to explore the TITH model's behaviour in articular cartilage
      compression tests. The force response, fluid flow and displacement fields
      obtained with the TITH model were compared with the classical linear elastic,
      isotropic, homogeneous (IH) model, showing that the IH model is unable to predict
      the non-uniform behaviour of the tissue. Based on considerations that the
      mechanical stability of the tissue depends on its topological and microstructural
      properties, our long-term goal is to clearly understand the stability conditions
      in topological terms, and the relationship with the growth and remodelling
      mechanisms in the healthy and diseased tissue.

PMID- 16084202
TI  - A numerical assessment of wall shear stress changes after endovascular stenting.
AB  - This theoretical/numerical study aims at assessing the haemodynamic changes
      induced by endovascular stenting. By using the classical one-dimensional linear
      pressure waves theory in elastic vessels, we first show that the modulus of the
      reflection coefficient induced by an endovascular prosthesis is most likely small
      since it is proportional to the stent-to-wavelength ratio. As a direct
      consequence, the wall motion of the elastic (stented) artery can be prescribed a
      priori and the coupled fluid-structure problem does not have to be solved for
      assessing the haemodynamic changes due to stenting. Several 2D axisymetric
      calculations are performed to solve the unsteady incompressible Navier-Stokes
      equations on moving meshes for different types of (stented) arteries. The
      numerical results suggest that endovascular stenting increases the systo
      diastolic variations of the wall shear stress (by 35% at the middle of the stent,
      by almost 50% in the proximal transition region). Additional calculations show
      that over-dilated stents produce less haemodynamic perturbations. Indeed, the
      increase of the amplitude of the wall shear stress variations over the cardiac
      cycle is only 10% when the stent radius is equal to the radius of the elastic
      artery at systole (instead of being equal to the mean artery radius).

PMID- 16084203
TI  - The minimum number of muscles to control a chain of joints with and without
      tenodeses, arthrodeses, or braces--application to the human finger.
AB  - While the underlying principles of controlling a single joint have been well
      described, the principles of simultaneously controlling multiple joints have not
      been comprehensively addressed in the literature of reconstructive hand surgery.
      This article analyzes (1) how many muscles are minimally required to fully
      control a chain of joints with in total N Degrees of Freedom (DoF), and (2) to
      what degree tenodeses, arthrodeses or braces can reduce the required number of
      muscles. It is demonstrated by mathematical analysis and illustrated by examples
      that the minimal number of muscles to control a chain of N DoF is N + 1. The
      number of muscles required for control can be reduced by mechanisms that reduce
      the number of DoF in the chain. (i) An arthrodesis is a permanent surgical
      fixation of a joint. An arthrodesis eliminates as many DoF in the chain as the
      arthrodized joints contributed. (ii) Tenodeses are coordinative tendon
      constructions. Each independent tenodesis eliminates one DoF from the chain.
      (iii) Braces are removable external supports. They eliminate as many DoF for
      muscle control as they immobilize. These principles are applied to illustrate the
      fundamental importance of tendinous structures in control in the human finger.
      Being able to determine the minimum number of muscles needed for multiarticular
      control gives additional knowledge in the design of functional reconstruction.

PMID- 16084204
TI  - Influence of an asymmetrical body weight distribution on the control of
      undisturbed upright stance.
AB  - Postural asymmetry in humans is generally associated with different pathologies.
      However, its specific influence on undisturbed upright stance is poorly
      understood. To evaluate its separate effects on each support, the centre of
      pressure (CP) displacements were recorded through two force platforms. In a
      second step, the complex resultant centre of pressure trajectories (CP(Res)) were
      computed and decomposed into two elementary components: the horizontal
      displacements of the centre of gravity (CG(h)) and the difference in the plane of
      support between the vertical projection of CG(h) and CP(Res) (CP-CG(v)). These
      motions were then processed through a frequency analysis and modelled as
      fractional Brownian motion to gain some additional insight into their spatio
      temporal organisation. Ten healthy adults were tested in three conditions
      consisting of various weight distributions. The quality of the mechanism involved
      in the control of the unloaded support CP motions appears to decrease as the
      asymmetry becomes more pronounced. To be precise, larger increases of the CP
      displacements are observed for the unloaded support compared to the loaded one.
      As a result, the CP(Res) motions are themselves augmented in the ML direction,
      inducing in turn larger CG(h) and CP-CG(v) motions. Postural asymmetry thus
      constitutes an important constraint on the control of upright undisturbed stance
      by generating changes in the control of both supports and by reducing the
      efficiency of the hip load/unload mechanisms. On the other hand, by inducing
      larger body sways, postural asymmetry necessitates higher energy expenditure and
      the setting of particular control mechanisms.

PMID- 16084205
TI  - Individuality and reproducibility in high-speed motion of volleyball spike jumps
      by phase-matching and averaging.
AB  - For analysis of knee injuries in volleyball, we developed a system to obtain
      kinematic waveforms about the high-speed motion of volleyball spike jumps that
      could examine their individuality and reproducibility, with phase-matching and
      averaging. The form of six female players was recorded in two sessions of ten
      jumps each, with a video motion-analysis system, VICON, at the sampling frequency
      of 240 Hz. To identify individual jump characteristics despite differences from
      jump to jump, we averaged up to ten data sets with phases matched. For such
      matching, we defined and used a statistic, epsilon, as the arithmetic mean of all
      absolute differences in each of the angles at each time sampled, based on the
      least squares method. Statistical evaluation with adjusted coefficients of
      multiple determination and epsilon showed that intra-individual variation between
      the two sessions was significantly smaller than inter-individual variation; their
      means differed by more than 2 standard deviations (SD) and 3SD, respectively.
      Regression analysis showed that this system was reliable (p < 0.001). We
      concluded that the averaged data sets obtained by the system could embody the
      individuality of spike jumps, with satisfactory reproducibility.

PMID- 16084206
TI  - Blood velocity field numerical assessment using a GPL code in case of
      intravascular Doppler catheter affections: comparative analysis of different
      rheological models.
AB  - In the use of intravascular Doppler catheters, one of the most common techniques
      to study the coronary arteries, the velocity field measured is partially affected
      by the presence of the catheter itself inside the blood vessel. It is therefore
      fundamental to quantify the nature of this disturbance. This paper treats a
      numerical investigation of the problem considering the hypothesis of blood as a
      Newtonian, Cassonian and Power Law fluid, comparing the results. The code used
      for numerical simulation is a General Public License Finite Element code
      denominated TOCHNOG. The results obtained, realistic within the terms explained
      in the text, provide an insight in the rheological characterisation of blood
      flow.

PMID- 16084207
TI  - Experimental and modelling investigation of learning a fast elbow flexion in the
      horizontal plane.
AB  - Changes in the kinematic and electromyographic characteristics that occur while
      learning to move as fast as possible have been studied experimentally.
      Experimental investigation of what happens to the individual motor units (MUs) is
      more difficult. Access to each MU is impossible, and the recruitment and force
      developing properties of all individual MUs cannot be known. Thus, what is
      currently known about MU firing is based on experiments that have recorded
      relatively few MUs compared to what exists in the entire muscle. A recently
      developed muscle model (Raikova and Aladjov, 2002, J. Biomechanics, 35, 1123
      1135) composed of MUs with different properties can be used for such
      investigation. The process of learning fast elbow flexion in the horizontal plane
      was simulated and the results were compared with experimentally measured data.
      Comparing the simulation results of the very first trial of a particular subject
      with those of the last trail (at the end of the learning process), it can be
      concluded that the speed of limb motion and muscle forces increase initially as a
      result of the more synchronous MUs activation and the increase of firing rate of
      active MUs. Further improvement necessitated an appreciable reduction in the
      motor task requirements (i.e. less muscle force and less MUs' activity) set in
      the computational algorithm by optimization criteria. This forced the next
      process-inclusion of additional MUs.

PMID- 16084208
TI  - Effects of compliance mismatch on blood flow in an artery with endovascular
      prosthesis.
AB  - The objective of this paper is to study the mechanical effects caused by the
      local stiffening of an artery (due to the vascular prosthesis, for instance). At
      the junction of the host artery and the more rigid implantant, the abrupt change
      in compliance creates an abnormal stress concentration that initiates an adaptive
      response in the vascular tissue. The roles of both fluid and solid mechanical
      phenomena must be considered in the prosthesis design optimization. In this
      context, even the simple models could provide helpful tools for designing
      process. We present here a model of blood flow in compliant vessel. The artery is
      supposed to be an orthotropical thin elastic shell. We obtain the solution by
      matched asymptotic expansions. The results prove the high flexure concentration
      close to the compliance jump. It is shown that the use of orthotropical graft may
      reduce the peak value of these shear forces to a remarkable extent. Waves
      reflected from the suture and pressure increase in the prosthesis are discussed.
      Compliance mismatch is shown to reduce the peak value of maximal wall shear
      stress.

PMID- 16084209
TI  - Tensile properties of embryonic epithelia measured using a novel instrument.
AB  - We present the first measurements of the tensile properties of embryonic
      epithelia, data that are crucial to understanding the mechanics of morphogenetic
      movements. Fine wires were glued to the surface of an intact, live embryo using
      cyanoacrylate glue, after which the epithelium between the wires was separated
      from the remainder of the embryo by microsurgery. The wires were then separated
      from each other in 0.1 microm steps under computer control in order to elongate
      the tissue at a constant true strain rate. Force was determined from the degree
      of bending in the wires, and a real-time, image-based feedback system corrected
      for reductions in elongation that would otherwise have been caused by wire
      flexure. The instrument was used to determine the tensile properties of epidermis
      and neuroepithelia from early-stage embryos of the axolotl (Ambystoma mexicanum),
      a type of amphibian. Monolayer specimens as small as 300 by 500 microm were
      elongated at physiological strain rates of 5-30% per hour, and the effects of
      developmental stage, epithelium type, specimen origin, direction of elongation
      and strain rate were investigated. True strains as high as 50% were observed
      before tearing began and equivalent moduli for the initial, linear portion of the
      load resultant versus strain curves ranged from 1 x 10(-3) to 8 x 10(-3) N/m.

PMID- 16084210
TI  - In vivo contact areas of the knee in patients with patellar subluxation.
AB  - OBJECTIVE: Ex vivo studies have suggested that cartilage contact areas and
      pressure are of high clinical relevance in the etiology of osteoarthritis in
      patients with patellar subluxation. The aims of this study were therefore to
      validate in vivo measurements of contact areas with 3D open magnetic resonance
      imaging (MRI), and to study knee joint contact areas in patients with patellar
      subluxation at different angles of knee flexion in comparison with healthy
      subjects. METHODS: 3D-MRI data sets of 12 healthy volunteers and eight patients
      with patellar subluxation were acquired using a standard clinical (1.5 T) and an
      open (0.2 T) MRI scanner. We compared femoro-patellar and femoro-tibial contact
      areas obtained with two different sequences from open MRI [dual-echo-steady-state
      (DESS) and fast-low-angle-shot (FLASH) sequences] with those derived from
      standard clinical 1.5 T MRI. We then analyzed differences in joint contact areas
      between healthy subjects and patients with patellar subluxation at 0 degree, 30
      degrees, and 90 degrees of knee flexion using open MRI. RESULTS: The correlation
      of the size of contact areas from open MRI with standard clinical MRI data ranged
      from r = 0.52 to 0.92. Open-MRI DESS displayed a smaller overestimation of joint
      contact areas (+21% in the femoro-patellar, +12% in the medial femoro-tibial, and
      +19% in the lateral femoro-tibial compartment) than FLASH (+40%, +37%, +30%,
      respectively). The femoro-patellar contact areas in patients were significantly
      reduced in comparison with healthy subjects (-47% at 0 degree, -56% at 30
      degrees, and -42% at 90 degrees of flexion; all p < 0.01), whereas no significant
      difference was observed in femoro-tibial contact areas. CONCLUSIONS: Open MRI
      allows one to quantify joint contact areas of the knee with reasonable accuracy,
      if an adequate pulse sequence is applied. The technique permits one to clearly
      identify differences between patients with patellar subluxation and healthy
      subjects at different flexion angles, demonstrating a significant reduction and
      lateralization of contact areas in patients. In the future, application of this
      in vivo technique is of particular interest for monitoring the efficacy of
      different types of surgical and conservative treatment options for patellar
      subluxation.

PMID- 16084211
TI  - Design and demonstration of a dynamometric horseshoe for measuring ground
      reaction loads of horses during racing conditions.
AB  - Because musculoskeletal injuries to racehorses are common, instrumentation for
      the study of factors (e.g. track surface), which affect the ground reaction loads
      in horses during racing conditions, would be useful. The objectives of the work
      reported by this paper were to (1) design and construct a novel dynamometric
      horseshoe that is capable of measuring the complete ground reaction loading
      during racing conditions, (2) characterize static and dynamic measurement errors,
      and (3) demonstrate the usefulness of the instrument by collecting example data
      during the walk, trot, canter, and gallop for a single subject. Using electrical
      resistance strain gages, a dynamometric horseshoe was designed and constructed to
      measure the complete ground reaction force and moment vectors and the center of
      pressure. To mimic the load transfer surface of the hoof, the shape of the
      surface contacting the ground was similar to that of the solar surface of the
      hoof. Following static calibration, the measurement accuracy was determined. The
      root mean squared errors (RMSE) were 3% of full scale for the force component
      normal to the hoof and 9% for force components in the plane of the hoof. The
      dynamic calibration determined that the natural frequency with the full weight of
      a typical horse was 1744 Hz. Example data were collected during walking on a
      ground surface and during trotting, cantering, and galloping on a treadmill. The
      instrument successfully measured the complete ground reaction load during all
      four gaits. Consequently the dynamometric horseshoe is useful for studying
      factors, which affect ground reaction loads during racing conditions.

PMID- 16084212
TI  - Evaluation of an electromagnetic position tracking device for measuring in vivo,
      dynamic joint kinematics.
AB  - An electromagnetic position tracking device was evaluated to determine its static
      and dynamic accuracy and reliability for applications related to measuring in
      vivo joint kinematics. The device detected the position and orientation of small
      coiled sensors, maintained in an electromagnetic field. System output was
      measured against known translations or rotations throughout the measurement
      volume. Average translational errors during static testing were 0.1 +/- 0.04, 0.2
      +/- 0.17, and 0.8 +/- 0.81 mm (mean+/-SD) for sensors 50, 300, and 550 mm away
      from the field generator, respectively. Average rotational errors were 0.4 +/-
      0.31 degrees, 0.4 +/- 0.21 degrees, and 0.9 +/- 0.85 degrees (mean +/- SD) for
      sensors located at the same distances. Since we intended to use this system in an
      animal walking on a treadmill, we incrementally moved the sensors under various
      treadmill conditions. The effects of treadmill operation on translational
      accuracy were found to be negligible. The effects of dynamic motions on sensor-to
      sensor distance were also assessed for future data collection in the animal.
      Sensor-to-sensor distance showed standard deviations of 2.6 mm and a range of 13
      mm for the highest frequency tested (0.23 Hz). We conclude that this system is
      useful for static or slow dynamic motions, but is of limited use for obtaining
      gait kinematics at higher speeds.

PMID- 16084213
TI  - Mechanics of the anterior drawer test at the ankle: the effects of ligament
      viscoelasticity.
AB  - The anterior drawer test at the human ankle joint is a routine clinical
      examination. The relationship between the mechanical response of this joint and
      the flexion angle was elucidated by a recent mathematical model, using purely
      elastic mechanical characteristics for the ligament fibres. The objective of the
      present work was to assess the effect of ligament viscoelasticity on the force
      response of the ankle joint for anterior displacements of the foot relative to
      the tibia, at different ankle flexion positions. A viscoelastic model of the
      ligaments from the literature was included in the recently proposed mathematical
      model. Drawer tests were simulated at several flexion angles and for increasing
      velocities of the imposed anterior displacement. The stiffness of the model ankle
      joint increased only modestly with velocity. The response force found for a 6mm
      displacement at 20 degrees plantarflexion increased by only 13% for a one hundred
      fold increase in velocity from 0.1 to 10 mm/s. The flexion angle was confirmed as
      the most influential parameter in the mechanical response of the ankle to
      anterior drawer test.

PMID- 16084214
TI  - A non-invasive method of tendon force measurement.
AB  - The ability to measure the forces exerted in vivo on tendons and, consequently,
      the forces produced by muscles on tendons, offers a unique opportunity to
      investigate questions in disciplines as varied as physiology, biomechanics,
      orthopaedics and neuroscience. Until now, tendon loads could be assessed directly
      only by means of invasive sensors implanted within or attached to these
      collagenous structures. This study shows that the forces acting on tendons can be
      measured, in a non-invasive way, from the analysis of the propagation of an
      acoustic wave. Using the equine superficial digital flexor tendon as a model, it
      is demonstrated that the velocity of an ultrasonic wave propagating along the
      main axis of a tendon increases with the force applied to this tendon.
      Furthermore, we show that this velocity measurement can be performed even in the
      presence of skin overlying the tendon. To validate this measurement technique in
      vivo, the ultrasonic velocity plots obtained in the Achilles tendon at the walk
      were compared to the loads plots reported by other authors using invasive
      transducers.

PMID- 16084215
TI  - Inexpensive color evaluation of dye-based pressure-sensitive films for plantar
      studies.
AB  - Dye-based pressure-sensitive films are advantageous in plantar pressure studies
      due to their ease of use, cost-effectiveness, and ability to produce measurements
      within the shoe. To circumvent the use of proprietary equipment and software to
      relate the dye-stained film to load, an alternative approach of using a
      conventional flatbed scanner and generic image processing software is attempted
      here instead. The technique revealed high linear increasing and decreasing trends
      for the respective red and blue normalized intensities (R(2) > 0.95) and low
      standard deviation in all readings (<0.06) overall. By subtracting the blue from
      the red normalized intensity, it was discovered that the measurement sensitivity
      could be doubled. The results here confirm the viability of using a conventional
      flatbed scanner and generic image processing software to relate the dye-stained
      pressure films to load. The adoption of this approach promises substantial cost
      savings.

PMID- 16084216
TI  - Laser capture microdissection and single-cell RT-PCR without RNA purification.
AB  - Chronic infectious diseases of the central nervous system (CNS) are characterized
      by intrathecal synthesis of increased amounts of immunoglobulin G (IgG) directed
      against the agent that causes disease. In other inflammatory CNS diseases such as
      multiple sclerosis and CNS sarcoid, the targets of the humoral immune response
      are uncertain. To identify the IgGs expressed by individual CD38(+) plasma cells
      seen in human brain sections, we merged the techniques of laser capture
      microdissection (LCM) and single-cell RT-PCR. Frozen brain sections from a
      patient who died of subacute sclerosing panencephalitis (SSPE), were rapidly
      immunostained and examined by LCM to dissect individual CD38(+) cells. After cell
      lysis, we developed two techniques for reverse-transcription (RT) of unpurified
      total RNA in the cell lysates. The first method performed repeated and rapid
      freeze-thawing, followed by centrifugation of the cell lysate into tubes for
      subsequent RT. The second, more successful method performed RT in situ on
      detergent-solubilized cells directly on the cap surface; subsequent nested PCR
      identified heavy and light chain sequences expressed by two-thirds of
      individually isolated plasma cells. These techniques will streamline the
      identification of gene expression products in single cells from complex tissues
      and have the potential to identify IgGs expressed in the CNS of inflammatory
      diseases of unknown etiology.

PMID- 16084217
TI  - Recommendations for the registration of agents to be used in the prevention and
      treatment of glucocorticoid-induced osteoporosis: updated recommendations from
      the Group for the Respect of Ethics and Excellence in Science.
AB  - OBJECTIVES: The Group for the Respect and Excellence in Science (GREES) has
      reviewed and updated their recommendations for clinical trials to evaluate the
      efficacy and safety of new chemical entities to be used in the treatment and
      prevention of glucocorticoid-induced osteoporosis (GIOP). METHODS: Consensus
      discussion of the committee. RESULTS: With the exception of steroid use
      posttransplantation, there is no need to differentiate between underlying
      diseases. Prevention and treatment for GIOP are dependent on exposure to
      glucocorticoids rather than T-scores as in postmenopausal osteoporosis (PMO). If
      fracture data are obtained for PMO, it need not be repeated for GIOP, relying
      instead on bone mineral density (BMD) trials of at least 1 year. GREES recommends
      several changes in the previous guidance for GIOP. The committee saw no need to
      repeat preclinical studies if those have been previously done to assure bone
      quality in PMO. Similarly, phase I and phase II trials, if careful dose selection
      has been done for PMO, should not be repeated. The "prevention" and "treatment"
      claims should remain. Since the most recent evidence suggests significant
      increase in fracture risk for daily doses of prednisone of 5 mg/day or
      equivalent, clinical trials should concentrate on patients receiving at least
      this daily dosage. The emergence of bisphosphonates as the reference treatment,
      together with the rapid bone loss and high fracture incidence in glucocorticoid
      users, necessitates recommending a noninferiority trial design with lumbar spine
      BMD as the primary endpoint after 1 year. CONCLUSIONS: Registration of new
      chemical entities to be used in the management of GIOP should be granted, based
      on a 1-year noninferiority trial, using BMD as primary outcome and alendronate or
      risedronate as comparator. Demonstration of antifracture efficacy should have
      been previously demonstrated in PMO.

PMID- 16084218
TI  - Editorial: should we evaluate insulin sensitivity in rheumatoid arthritis?

PMID- 16084219
TI  - Rheumatoid arthritis: a disease associated with accelerated atherogenesis.
AB  - OBJECTIVES: Rheumatoid arthritis (RA) is a systemic inflammatory disease
      associated with an increased prevalence of coronary heart disease and a high
      cardiovascular (CV) mortality. In this article, a review of mechanisms implicated
      in the development of accelerated atherogenesis in RA was performed. The
      potential role of treatment to reduce the incidence of CV events in RA was also
      discussed. METHODS: Retrospective review of the literature. The potential
      mechanisms implicated in the development of accelerated atherogenesis in RA,
      information on carotid ultrasonography, and the potential implication of
      treatment to prevent accelerated atherogenesis in individuals with RA were
      examined. RESULTS: Endothelial dysfunction, which is an early step in the
      development of atherosclerosis, has been observed in patients with RA.
      Deleterious effects resulting from persistent chronic inflammation may lead to
      endothelial dysfunction, insulin resistance, and a dyslipidemic pattern in these
      patients. Other mechanisms different from those related to classic atherogenesis
      risk factors, such as hyperhomocysteinemia and increased oxidative stress, are
      considered to be implicated in the pathogenesis of atherosclerosis in RA.
      Increased carotid intima-media thickness and carotid plaques have been found in
      RA patients compared with matched controls. Active MTX treatment of the disease
      has been associated with decreased CV mortality. Additional drugs such as statins
      may be considered in the management of these patients. CONCLUSIONS: The increased
      prevalence of CV mortality rate in RA cannot only be explained by the presence of
      traditional atherosclerotic risk factors. A chronic inflammatory response may
      promote the development of accelerated atherogenesis in these patients. Active
      treatment of the disease is required to reduce the risk of developing CV
      complications in individuals with RA.

PMID- 16084220
TI  - Duplex study of the carotid and femoral arteries of patients with rheumatoid
      arthritis: a controlled study.
AB  - BACKGROUND: "Ultrasonic biopsy" (U-B) is a noninvasive screening technique to
      detect early atherosclerotic plaques and arterial wall changes. AIM: To identify
      atherosclerosis (AS) in the common carotid artery (CCA) and common femoral artery
      (CFA) of patients with rheumatoid arthritis (RA) and their matched controls.
      METHODS: Fifty-seven consecutive RA patients were enrolled in the study. Controls
      were matched by age, sex, ethnicity, and AS risk factors. All patients and
      controls underwent U-B study of the CCA and CFA. The U-B features were classified
      and scored as follows: Class A, normal (score 0); Class B, interface disruption
      (score 2); class C, intima-media (I-M) granulation (score 4); Class D, plaque
      without hemodynamic disturbance (score 6); Class E, stenotic plaque (score 8);
      and Class F, plaque with symptoms (score 10). Total score per patient was
      calculated. Classes A-B indicate an intact media or minimal interphase changes;
      classes D-F point to a significant medial involvement. Class C signifies a
      borderline lesion, with a potential for regression to normal, being unchanged, or
      progression to a plaque. RESULTS: Mean ages were 52.1 years for RA and 51.4 years
      for controls (P = 0.81). Eighty-six percent of the patients and 85% of controls
      were women. The mean disease duration of RA was 12.8 years. Frequencies of risk
      factors among the RA patients compared with controls were hypertension (28%
      versus 32%), smoking (37% versus 29%), dyslipidemia (23% versus 25%), diabetes
      mellitus (DM) (14% versus 14%), and family history of cardiovascular disease
      (CVD) (4% versus 7%). Forty-five percent of the RA patients had at least a single
      Classes D-F lesion (plaque) in 1 of the 4 vessels tested, compared with 40% in
      the control group (P = 0.19). The mean total U-B scores of the RA patients and
      controls were not significantly different (8.87 versus 9.49, P = 0.7). Univariate
      analyses have shown that the development of plaques in RA patients was associated
      with age >50 years, disease duration, hypertension, dyslipidemia, and smoking.
      Multivariate analysis found plaques to be strongly associated with age above 50
      years and dyslipidemia. CONCLUSION: In unselected RA patients, besides classic AS
      risk factors, older age and longstanding disease may help predict the development
      of a severe morphological expression of AS.

PMID- 16084221
TI  - Role of the growth hormone/insulin-like growth factor-1 paracrine axis in
      rheumatic diseases.
AB  - OBJECTIVES: Hypothalamic-pituitary axis abnormalities have been associated with
      systemic disturbances in several rheumatic diseases. Longitudinal analysis of
      erythrocyte, serum, urinary and synovial fluid growth hormone (GH), insulin-like
      growth factor-1 (IGF-1), and somatostatin levels could provide important
      surrogate measures of disease activity in rheumatic diseases. METHODS: The
      authors reviewed the population and longitudinal studies literature on GH, IGF-1,
      and somatostatin levels in rheumatic disorders using the PubMed and Medlines
      databases from the National Library of Medicine. In addition to the literature
      search, primary data were analyzed for basal somatostatin levels in patients with
      hand, knee, and spine osteoarthritis (OA) as well as primary and secondary hip
      OA. RESULTS: A review of the literature supports the view that hypothalamic
      pituitary axis dysfunction accompanies clinical symptoms in many rheumatic
      diseases. In studies from our laboratory, serum GH levels were elevated in
      patients with OA, rheumatoid arthritis (RA), fibromyalgia, and diffuse idiopathic
      skeletal hyperostosis but not in patients with gout, pseudogout, or systemic
      lupus erythematosus. In OA and RA, synovial fluid GH levels exceeded serum GH
      levels. However, the literature remains controversial regarding the significance
      of changes in IGF-1 levels in rheumatic disorders. Many studies support an
      inverse relationship between age and IGF-1. Elevated serum GH levels in various
      rheumatic diseases were not coupled to changes in serum IGF-1 in diffuse
      idiopathic skeletal hyperostosis, RA, and fibromyalgia. In particular, serum IGF
      1 levels in OA were shown to be lower or no different compared with age-matched
      normal subjects. Further, in OA, impaired articular chondrocyte response to IGF-1
      was attributed, in part, to low synovial fluid IGF-1 that further compromised IGF
      1 chondrocyte responses as a result of increased levels of synovial fluid IGF-1
      binding proteins. Of note, serum somatostatin levels and "specific" somatostatin
      receptor levels were often lower in RA and systemic lupus erythematosus, but
      basal serum somatostatin levels were generally not altered in OA. CONCLUSIONS:
      The results of these analyses support the view that some rheumatic diseases such
      as OA and diffuse idiopathic skeletal hyperostosis, heretofore considered to be
      purely focal and degenerative, could be reclassified as systemic metabolic
      disturbances. We propose that serum GH, IGF-1, and somatostatin levels be
      monitored on a longitudinal basis during the course of medical therapy of
      rheumatic diseases to determine the extent to which changes in clinical symptoms
      (exemplified by reduced pain and inflammation and improved range of joint motion)
      are accompanied by changes in the basal concentration of these
      hypothalamic/pituitary-related hormones.

PMID- 16084222
TI  - Autoantibodies in systemic sclerosis.
AB  - OBJECTIVES: To describe the clinical, laboratory, and prognostic features
      associated with the scleroderma-specific autoantibodies. METHODS: Using the
      Pittsburgh Scleroderma Databank, all consecutive patients seen between 1980 and
      1995 who had autoantibody studies performed were studied. Anticentromere
      antibodies (ACA), antitopoisomerase (TOPO), anti-U1-RNP (U1-RNP), anti-RNA
      Polymerase III (Pol 3), anti-U3-RNP (U3-RNP), anti-Th/To (Th/To), and anti-Pm/Scl
      (Pm/Scl) were determined according to previously described methods. The frequency
      of clinical features, organ system outcomes, and survival within the patients
      with a specific antibody were cumulative over the course of the disease. The
      frequency of a specific feature was compared across groups to identify
      significant manifestations and outcomes in patients with a specific antibody.
      RESULTS: Some demographic, clinical, and organ system findings were associated
      with the specific antibody, and other features with the scleroderma subtype
      (limited cutaneous or diffuse cutaneous scleroderma). U3-RNP, U1-RNP, and TOPO
      were seen more commonly in African-American patients, and ACA was seen in older,
      female Caucasians. Muscle inflammation was seen in patients with U1-RNP and U3
      RNP. Digital tip ulcers and digital tuft resorption were seen more frequently in
      those with ACA and TOPO. A vasculopathy causing pulmonary hypertension typically
      occurs with ACA and pulmonary fibrosis with TOPO; however, both types of lung
      disease were seen in patients with nucleolar antibodies, Th/To and U3-RNP.
      Importantly, severe interstitial fibrosis was rarely seen in cases with Pol 3.
      Renal crisis was strongly associated with Pol 3. Survival within limited
      scleroderma was decreased in the Th/To patients compared with ACA patients.
      Within the diffuse scleroderma group, patients with Pol 3 had the best survival.
      CONCLUSIONS: Scleroderma autoantibodies are associated with very specific
      demographic, clinical, organ system, and survival features. RELEVANCE: The
      determination of scleroderma autoantibodies may be helpful in assessing the
      prognosis, monitoring, and treatment of scleroderma patients.

PMID- 16084223
TI  - Retroperitoneal fibrosis and ankylosing spondylitis: which links?
AB  - OBJECTIVES: To report a case of retroperitoneal fibrosis (RPF) in a patient with
      ankylosing spondylitis (AS) and to review the medical literature for similar
      cases to detect possible links between the 2 diseases. METHODS: The presentation,
      clinical course, diagnostic work-up, and treatment of our patient are described,
      and the English and French medical literature from 1960 to 2000 is reviewed using
      a MEDLINE search for cases with coexisting RPF and spondyloarthritis. RESULTS:
      Our patient with AS had RPF, which mimicked rectal cancer with retroperitoneal
      and vertebral metastases. Special attention is paid to the unusual clinical
      presentation, the multistep diagnostic process, and the therapeutic strategy
      which was both radiologically and histologically successful. Literature review
      revealed 18 cases of concomitant RPF and spondyloarthritis, mainly AS. Patients
      were more frequently male (M/F, 3/1) and developed spondyloarthritis several
      years before RPF. CONCLUSIONS: RPF may result from a local immune response to
      products of aortic atheromatous plaques, with subsequent periaortic deposition of
      fibrous tissue. However, the clinical features and the frequent association with
      other fibrosing disorders suggest that RPF is a systemic inflammatory condition.
      The role of AS-associated aortitis in the development of RPF warrants
      consideration.

PMID- 16084224
TI  - Autoimmune hepatitis and pregnancy: a rheumatologist's dilemma.
AB  - OBJECTIVES: To review the course, predisposing risk factors, treatment employed,
      and complications of autoimmune hepatitis (AIH) during pregnancy. Maternal and
      fetal outcomes will be discussed. METHODS: We reviewed the literature from
      February 1966 to January 2004 using MEDLINE and the key words autoimmune
      hepatitis, chronic active hepatitis, lupoid hepatitis, and pregnancy. An
      additional case of ours was included as she had AIH since childhood with
      worsening of liver disease during pregnancy. RESULTS: Including the present case,
      58 pregnant women with AIH were reported in 17 case reports and series. In the
      101 pregnancies documented in these cases, there were 47 flare-ups, 5 clinical
      improvements, 45 stabilizations of the disease during pregnancy, and 4 cases in
      which the disease course was not reported. Two maternal deaths occurred. A
      perinatal mortality of 4% and 19 fetal deaths were described. Most women were
      treated with prednisone alone; however azathioprine was used in a number of
      patients. CONCLUSIONS: Pregnancy course in patients with AIH is unpredictable.
      AIH exacerbates in some patients and is associated with a high rate of fetal
      complications including prematurity and death. Low-dose prednisone seems to be
      the preferred treatment. The use of azathioprine must be individualized and
      further studies are needed to better define its role and safety during pregnancy
      in patients with AIH. RELEVANCE: A better understanding of the course of
      pregnancy in patients with AIH should help design appropriate therapeutic schemes
      to improve pregnancy outcomes for both mother and fetus.

PMID- 16084225
TI  - Evaluation of disease severity in familial Mediterranean fever.
AB  - OBJECTIVE: To establish a new, objective, statistically based severity score for
      familial Mediterranean fever (FMF). METHODS: One hundred consecutive FMF patients
      were evaluated independently by 2 FMF experts for severity of their disease and
      were assigned to 1 of 3 severity levels: mild, intermediate, or severe. Nine
      candidate criteria, reflecting objective suffering and disability, were analyzed
      to determine their weight for patient placement in the 3 predefined severity
      groups. RESULTS: Candidate criteria best differentiating between the 3 patient
      categories were the frequency of attacks, the number of sites affected during an
      attack and during the course of the disease, and the duration of the attacks.
      These criteria were applied in a classification-tree model to establish a new FMF
      severity score (F-SS). The first set of F-SS (F-SS-1) was highly sensitive and
      specific. Integrating F-SS-1 with clinical parameters strongly associated with
      disease severity resulted in a simplified score, the second set of F-SS (F-SS-2).
      CONCLUSIONS: New, useful, objective, and valid severity scores were established
      and found to distinguish between patients with mild, intermediate, and severe
      diseases with high sensitivity and specificity. RELEVANCE: The F-SS established
      may be important for treatment decisions, prognosis evaluation, and comparative
      analysis of patient populations.

PMID- 16084226
TI  - Anti-CRP autoantibody levels correlate with disease activity in systemic lupus
      erythematosus.

PMID- 16084227
TI  - Osteoarthritis: an overview of the disease and its treatment strategies.
AB  - Osteoarthritis (OA) is currently defined by the American College of Rheumatology
      as a "heterogeneous group of conditions that leads to joint symptoms and signs
      which are associated with defective integrity of articular cartilage, in addition
      to related changes in the underlying bone at the joint margins." Its prevalence
      after the age of 65 years is about 60% in men and 70% in women. The etiology of
      OA is multifactorial, with inflammatory, metabolic, and mechanical causes. A
      number of environmental risk factors, such as obesity, occupation, and trauma,
      may initiate various pathological pathways. OA indicates the degeneration of
      articular cartilage together with changes in subchondral bone and mild
      intraarticular inflammation. The principal treatment objectives are to control
      pain adequately, improve function, and reduce disability. Acetaminophen is
      frequently used for symptomatic OA with mild to moderate pain. Nonsteroidal
      antiinflammatory drugs (NSAIDs) are more effective in the case of moderate-severe
      pain, but they have an increased risk of serious upper gastrointestinal adverse
      events. The newer cyclooxygenase COX-2 specific inhibitors (Coxibs) are as
      efficacious as traditional NSAIDs and have a better gastrointestinal safety
      profile. Other compounds (eg, chondroitin sulfate, diacerein, glucosamine
      sulfate) have a symptomatic effect that is slower and less than that of NSAIDs.
      The structure-modifying effects of drugs are currently being evaluated, and both
      glucosamine sulfate and diacerein have been shown in some trials to have a
      beneficial structural effect. Nonpharmacological interventions are frequently and
      widely used in the management of OA patients, but there is little evidence that
      they are effective: the best studied and most successful nonpharmacological
      interventions are patient education, self-management, and exercise. There is some
      evidence for the pain-relieving efficacy of thermotherapy and transcutaneous
      electrical nerve stimulation (TENS) but not of electrotherapy, acupuncture,
      homeopathy, or manual therapy. The value of interventions aimed at improving
      function and maximizing independence (occupational therapy, walking aids,
      workplace adaptation) is also unclear. The disease course and patient's
      requirements often change over time, thus requiring a periodic review and
      readjustment of therapy rather than the rigid continuation of a single treatment.

PMID- 16084228
TI  - The characteristics of symptomatic osteoarthritis in general and specialist
      practice in Italy: design and methods of the AMICA Study.
AB  - OBJECTIVE: The diagnostic and clinical approach to osteoarthritis (OA) of the
      hand, knee, and hip in general practice and specialist practice in Italy as
      determined by the AMICA project. METHODS: Eligible subjects were identified among
      patients aged > or =50 years consecutively observed by their general practitioner
      (GP) or a specialist during the study period for diagnosis or treatment of
      symptomatic OA of the hand, knee, or hip. OA was diagnosed according to the
      American College of Rheumatology clinical criteria. The general characteristics
      and symptoms of all eligible subjects were evaluated. Data were also collected on
      diagnostic work-up and treatment. All subjects were also asked to quantify the
      intensity of their OA-related pain according to a 100-mm visual analog scale
      (VAS) where 0 = no pain and 100 = the worst pain. RESULTS: A total of 2764 GP and
      331 specialists (98 rheumatologists, 166 orthopedic surgeons, and 67 other
      specialists) participated in the study. The area of residence was largely similar
      for both GPs and specialists and covered all of Italy. A total of 25,589 valuable
      subjects with OA were identified by the GPs, while 3543 were identified by the
      specialists. Among the latter, 1777 were identified by orthopedic surgeons, 1067
      by rheumatologists, and 699 by other specialists (specialists in physical
      medicine and internal medicine, geriatricians, etc). The median age of patients
      identified by GPs was 70 years; the corresponding value was 66 years for the
      patients identified by the orthopedic surgeons, 69 years by the rheumatologists,
      and 68 years by other specialists. Overall, 69% of patients were women: this
      proportion was similar among patients identified by the GPs, the orthopedic
      surgeons, and other specialists, but patients identified by the rheumatologists
      were women in 80% of cases. Patients observed by the specialists had a higher
      level of education than those observed by GPs (P < 0.05). This finding was
      partially explained by the younger age of the patients observed by the
      specialists. CONCLUSIONS: This large data set reveals the attitudes of Italian
      GPs and specialists toward the diagnosis and treatment of OA of the hand, knee,
      and hip.

PMID- 16084229
TI  - Clinical presentation of osteoarthritis in general practice: determinants of pain
      in Italian patients in the AMICA study.
AB  - OBJECTIVE: To assess the clinical characteristics and determinants of pain
      observed by general practitioners (GPs) in Italian patients with osteoarthritis
      (OA) of the hand, hip, and knee. METHODS: The 2764 GPs participating in the study
      were asked to enroll 10 consecutive patients with OA diagnosed according to the
      American College of Rheumatology (ACR) clinical criteria. To standardize the
      diagnosis, the GPs received ad hoc training from musculoskeletal system
      specialists. A questionnaire evaluating demographic data, the clinical
      characteristics of OA, and previous diagnostic and therapeutic interventions was
      administered by the GPs. RESULTS: 25,589 evaluable patients were enrolled during
      a mean period of 2.8 weeks by the GPs: 17,567 women (69%) and 7878 men (31%). The
      most painful OA joints were the knee in 12,827 patients (54%), the hip in 5645
      patients (24%), and the hand in 5467 patients (23%)--percentages calculated on
      the 23,939 patients for whom this information was available. The weekly incidence
      of referrals to GPs for OA was higher for women and for knee OA. The median age
      of the patients was 70 years (range 50 to 104 years) and disease duration was 8.3
      +/- 7.10 years. The most frequent comorbidities were hypertension (53%), obesity
      (22%), osteoporosis (21%), type II diabetes mellitus (15%), and chronic
      obstructive pulmonary disease (13%). The median pain visual analog scale (VAS)
      score was higher for women than for men, for hip OA, and for generalized OA (GOA)
      than for knee and hand OA (P < 0.0001). Intense pain, defined as VAS readings of
      >60 mm, was increased in women only in the knee (OR = 1.24; 95% CI 1.15 to 1.34)
      and in GOA (OR = 1.17; 95% CI 1.03 to 1.33). It was also significantly increased
      in patients older than 70 years (OR = 1.46; 95% CI 1.39 to 1.54), those with a
      low educational level (OR = 1.44; 95% CI 1.36 to 1.5), a BMI of > or =30 (OR =
      1.52; 95% CI 1.42 to 1.61), a disease duration of more than 7 years (OR = 1.60;
      95% CI 1.52 to 1.68), comorbidities (OR = 1.61; 95% CI 1.5 to 1.73), and GOA (OR
      = 2.05; 95% CI 1.91 to 2.19). Manual occupations were associated with highly
      intense pain only in men. CONCLUSIONS: The results of this study underscore the
      major impact of OA on care in general practice, the high frequency of OA
      associated comorbidities, and the role of different risk factors in OA pain.

PMID- 16084230
TI  - Analysis of pharmacologic and nonpharmacologic prescription patterns of general
      practitioners and specialists in the AMICA study.
AB  - OBJECTIVE: To evaluate the prescription modalities of general practitioners (GPs)
      and specialists in symptomatic osteoarthritis (OA) patients enrolled in the AMICA
      study. PATIENTS AND METHODS: This study started in 2001 as a cohort investigation
      of OA patients seen by 2764 GPs and 316 specialists. Enrolled were 28,981
      patients with symptomatic OA of the hand, hip, or knee. RESULTS: GPs and physical
      medicine specialists treated OA less frequently with pharmacological therapy than
      rheumatologists (OR 0.35; CI 0.26 to 0.47) or orthopedic surgeons (OR 0.65; CI
      0.54 to 0.77). Pharmacological therapies (alone or in association with
      nonpharmacological modalities) were selected by 97% of the GPs, 96% of the
      rheumatologists, 94% of the orthopedic surgeons, and 85% of the physical medicine
      specialists. In comparison with GPs, all of the specialists more frequently used
      disease-modifying OA drugs (DMOADs) (rheumatologists: OR 6.86, CI 6.03 to 7.80;
      orthopedic surgeons: OR 2.20, CI 1.94 to 2.49; physical medicine specialists: OR
      2.11, CI 1.69 to 2.63). Nonpharmacological therapies were selected by 44% of the
      GPs, 54% of the rheumatologists, 71% of the orthopedic surgeons, and 90% of the
      physical medicine specialists. They were used alone uncommonly (by 3% of the GPs,
      3% of the rheumatologists, 6% of the orthopedic surgeons, and 15% of the physical
      medicine specialists). GPs use nonpharmacological treatment less than
      specialists: OR 0.53; CI 0.47 to 0.60 versus rheumatologists; OR 0.20; CI 0.18 to
      0.21 versus orthopedic surgeons; and OR 0.07; CI 0.05 to 0.09 versus physical
      medicine specialists. Ultrasound (US) (11%) and transcutaneous electrical nerve
      stimulation (TENS) (7%) were the nonpharmacological therapies most frequently
      prescribed by GPs. Among the specialists, physical medicine specialists most
      frequently prescribed US (35%) and TENS (21%); US was also preferred by
      rheumatologists, whereas the orthopedic surgeon's choice was magnetotherapy
      (21%). Exercises and other passive or active rehabilitation strategies were
      prescribed for only 13% of the patients seen by GPs, but all 3 categories of
      specialists prescribed exercises and manual techniques far more frequently:
      rheumatologists, OR 1.63: 1.40 to 1.63; orthopedic surgeons, OR 1.67: 1.48 to
      1.88; physical medicine specialists, OR 3.19: 2.66 to 3.82. CONCLUSIONS: Italian
      rheumatologists and orthopedic surgeons are the specialists who most frequently
      use pharmacological treatment for OA. Nonpharmacological treatment is used
      commonly among both GPs and specialists but rarely as single therapy. Exercise
      and passive or active rehabilitation strategies are not frequently prescribed,
      although they are recommended by all the published guidelines.

PMID- 16084231
TI  - Comorbid conditions in the AMICA study patients: effects on the quality of life
      and drug prescriptions by general practitioners and specialists.
AB  - OBJECTIVE: Osteoarthritis (OA) has been identified as the disease with the
      highest rate of comorbidities, which may increase the likelihood of disability.
      The AMICA study evaluated how the presence of a coexistent disease and/or its
      chronic pharmacological treatment influenced the prescription of pharmacological
      and nonpharmacological therapy in patients with OA. PATIENTS AND METHODS: The
      2764 general practitioners (GPs) and 316 specialists (98 rheumatologists, 166
      orthopedic surgeons, 52 physical medicine specialists) participating in the study
      were asked to enroll 10 consecutive patients with OA diagnosed according to the
      American College of Rheumatology clinical criteria. Information was collected
      regarding demographics, the clinical characteristics of OA, and previous
      diagnostic and therapeutic interventions. Pain intensity was assessed using a 100
      mm visual analog scale (VAS); the patients were also asked to report on their
      quality of life and joint function, as well as the presence of any concomitant
      disease and/or therapy. The influence of comorbidities on the quality of life,
      pain, and drug prescription was evaluated. RESULTS: A total of 29,132 evaluable
      patients was observed (25,589 recruited by GPs and 3543 by specialists). The most
      frequent comorbidities were hypertension (52%), osteoporosis (21%), type II
      diabetes mellitus (15%), and chronic obstructive pulmonary disease (12%);
      myocardial infarction and/or angina pectoris were present in 6% and peptic ulcer
      was present in 5%. Comorbidities were more frequent in older patients and, except
      in the case of hypertension, were closely related to more intense pain and a
      decreased quality of life; they were also generally associated with worsened
      joint function. The presence of peptic ulcer was associated with a reduction in
      the prescription of nonsteroidal antiinflammatory drugs (NSAIDs) (odds ratio (OR)
      0.61; confidence intervals (CI) 0.53 to 0.69) and the more frequent use of Coxibs
      (OR 1.15; CI 1.03 to 1.28) and simple analgesics (OR 1.42; CI 1.26 to 1.61), as
      well as with greater use of physical therapy. Hypertension was associated with a
      reduction in the prescription of physical therapy. NSAIDs and Coxibs were less
      frequently prescribed if the patients were on anticoagulant therapy (NSAIDs: OR
      0.86; CI 0.70 to 1.06; Coxibs: OR 0.77; CI 0.64 to 0.93). Gastroprotective
      therapy was more frequently used in patients treated with NSAIDs, Coxibs, and
      analgesics, with GPs giving greater preference to proton pump inhibitors than
      specialists. CONCLUSIONS: Comorbidities decrease the quality of life and worsen
      the joint function in OA patients. Comorbidities and their treatment generally do
      not influence the physician's choice of OA treatment, with the exception of
      peptic ulcer and anticoagulant therapy, both of which were associated with a
      reduction in the prescription of antiinflammatory drugs. There was a preferential
      use of Coxibs in patients with peptic ulcer, and an underuse of gastroprotective
      measures in OA patients treated with NSAIDs.

PMID- 16084232
TI  - Do physicians treat symptomatic osteoarthritis patients properly? Results of the
      AMICA experience.
AB  - OBJECTIVE: The main objective of the AMICA project was to photograph the Italian
      scenario of osteoarthritis (OA) and its treatment in general and specialty
      practice. The study was designed to evaluate their prescription modalities to
      determine whether they matched the recently proposed treatment guidelines for OA
      (ACR 2000; EULAR 2000; APS 2002). METHODS: The study involved 2764 general
      practitioners (GPs) and 316 specialists who enrolled a total of 25,589 patients
      with OA of the hand, knee, and hip. RESULTS: Pharmacological treatment alone was
      prescribed to 55% of the patients seen by GPs, 25% of those seen by
      rheumatologists, 8% of those seen by orthopedic surgeons, and 17% of those seen
      by physical medicine specialists (GPs versus specialists, P < 0.001). Specialists
      often prescribed a combined pharmacological and nonpharmacological approach
      (rheumatologists 51%, orthopedic surgeons 66%, physical medicine specialists
      76%). Concomitant comorbidities and their treatment do not seem to influence OA
      prescription modalities except for peptic ulcer and anticoagulant therapy. The
      presence of peptic ulcer was associated with a reduction in NSAID prescriptions
      (OR 0.61, CI 0.53 to 0.69) and more frequent use of Coxibs (OR 1.15, CI 1.03 to
      1.28) and simple analgesics (OR 1.42; CI 1.26 to 1.61), as well as physical
      therapy. NSAIDs and Coxibs also were less frequently prescribed if patients were
      receiving anticoagulant therapy (NSAIDs OR 0.86, CI 0.70 to 1.06; Coxibs: OR
      0.77; CI 0.64 to 0.93). Gastroprotective therapy was more frequently used in
      patients treated with NSAIDs, Coxibs, and analgesics. There was no significant
      difference in therapies prescribed for patients with hypertension or cardiac
      disease (myocardial infarction and/or angina pectoris). CONCLUSIONS: The
      published guidelines appear to be properly used by most of the physicians in
      terms of the pharmacological approach; however, the increased use of Coxibs has
      not reduced the amount of prescribed gastroprotection. No specific precautions
      were observed in the treatment of patients with hypertension or cardiac problems.
      Nonpharmacological treatments are mainly used in conjunction with medications and
      did not take into account the findings of evidence-based medicine. Continuing
      education of GPs and specialists caring for OA patients is essential.

PMID- 16084233
TI  - A stain on medical ethics.

PMID- 16084234
TI  - Adjuvant aromatase inhibitors for breast cancer.

PMID- 16084235
TI  - Multiresistant pulmonary infection in cystic fibrosis--prevention is better than
      cure.

PMID- 16084236
TI  - Pulmonary artery catheters in intensive care.

PMID- 16084237
TI  - Fast, simple, and low-cost test for drug-resistant pathogens.

PMID- 16084238
TI  - Surveillance of HIV and tuberculosis drug resistance.

PMID- 16084239
TI  - Novel pain relief via marine snails.

PMID- 16084240
TI  - Jennie Brand-Miller.

PMID- 16084242
TI  - Roy Meadow.

PMID- 16084243
TI  - Roy Meadow.

PMID- 16084244
TI  - Roy Meadow.

PMID- 16084245
TI  - Roy Meadow.

PMID- 16084246
TI  - Obesity in Latin America: similarity in the inequalities.

PMID- 16084247
TI  - Roy Meadow.

PMID- 16084248
TI  - Roy Meadow.

PMID- 16084249
TI  - Multiple pregnancy after assisted reproduction.

PMID- 16084250
TI  - Multiple pregnancy after assisted reproduction.

PMID- 16084253
TI  - Switching of postmenopausal women with endocrine-responsive early breast cancer
      to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial
      8 and ARNO 95 trial.
AB  - BACKGROUND: Tamoxifen has been the standard adjuvant treatment for postmenopausal
      women with hormone-responsive early breast cancer for more than 20 years.
      However, the third-generation aromatase inhibitor anastrozole has proven efficacy
      and tolerability benefits compared with tamoxifen when used as initial adjuvant
      therapy. We investigate whether women who have received a period of adjuvant
      tamoxifen would benefit from being switched to anastrozole. METHODS: We present a
      combined analysis of data from two prospective, multicentre, randomised, open
      label trials with nearly identical inclusion criteria. Postmenopausal women with
      hormone-sensitive early breast cancer who had completed 2 years' adjuvant oral
      tamoxifen (20 or 30 mg daily) were randomised to receive 1 mg oral anastrozole
      (n=1618) or 20 or 30 mg tamoxifen (n=1606) daily for the remainder of their
      adjuvant therapy. The primary endpoint was event-free survival, with an event
      defined as local or distant metastasis, or contralateral breast cancer. Analysis
      was by intention to treat. FINDINGS: 3224 patients were included in analyses. At
      a median follow-up of 28 months, we noted a 40% decrease in the risk for an event
      in the anastrozole group as compared with the tamoxifen group (67 events with
      anastrozole vs 110 with tamoxifen, hazard ratio 0.60, 95% CI 0.44-0.81,
      p=0.0009). Both study treatments were well tolerated. There were significantly
      more fractures (p=0.015) and significantly fewer thromboses (p=0.034) in patients
      treated with anastrozole than in those on tamoxifen. INTERPRETATION: These data
      lend support to a switch from tamoxifen to anastrozole in patients who have
      completed 2 years' adjuvant tamoxifen.

PMID- 16084254
TI  - Combination antibiotic susceptibility testing to treat exacerbations of cystic
      fibrosis associated with multiresistant bacteria: a randomised, double-blind,
      controlled clinical trial.
AB  - BACKGROUND: We did a randomised, double-blind, controlled clinical trial to
      prospectively assess whether use of combination antibiotic susceptibility testing
      improved clinical outcomes in patients with acute pulmonary exacerbations of
      cystic fibrosis who were infected with multiresistant bacteria. METHODS: 251
      patients with cystic fibrosis who were chronically infected with multiresistant
      gram negative bacteria gave sputum at 3-month intervals for conventional culture
      and sensitivity tests and for combination antibiotic susceptibility tests using
      multiple combination bactericidal antibiotic testing (MCBT). Patients who
      developed an exacerbation of pulmonary disease were randomised to receive a 14
      day course of any two blinded intravenous antibiotics chosen on the basis of
      either results from conventional sputum culture and sensitivity testing or the
      result of MCBT. The primary outcome was time from randomisation until the
      patient's next pulmonary exacerbation. Analysis was by intention-to-treat. This
      study is registered as an International Standard Randomised Controlled Trial,
      number ISRCTN60187870. FINDINGS: 132 patients had a pulmonary exacerbation and
      were randomised during the 4.5-year study period. The time to next pulmonary
      exacerbation was not prolonged in the MCBT-treated group (hazard ratio 0.86 in
      favour of the conventionally-treated group, 95% CI 0.60-1.23, p=0.40). There was
      no difference between the groups in treatment failure rate. After 14 days of
      intravenous antibiotic therapy, changes in lung function, dyspnoea, and sputum
      bacterial density were similar in both groups. INTERPRETATION: Antibiotic therapy
      directed by combination antibiotic susceptibility testing did not result in
      better clinical and bacteriological outcomes compared with therapy directed by
      standard culture and sensitivity techniques. The non-bactericidal effects of
      antibiotic therapy might play an important part in determining improvement in
      patients with cystic fibrosis pulmonary exacerbations.

PMID- 16084255
TI  - Assessment of the clinical effectiveness of pulmonary artery catheters in
      management of patients in intensive care (PAC-Man): a randomised controlled
      trial.
AB  - BACKGROUND: Over the past 30 years the pulmonary artery catheter (PAC) has become
      a widely used haemodynamic monitoring device in the management of critically ill
      patients, though doubts exist about its safety. Our aim was, therefore, to
      ascertain whether hospital mortality is reduced in critically ill patients when
      they are managed with a PAC. METHODS: We did a randomised controlled trial to
      which we enrolled 1041 patients from 65 UK intensive care units. We assigned
      individuals to management with (n=519) or without (n=522) a PAC. The timing of
      insertion and subsequent clinical management were at the discretion of the
      treating clinician. Intensive care units decided a priori to have the option of
      using an alternative cardiac output-monitoring device in control patients.
      FINDINGS: 1014 patients were eligible for analysis. We noted no difference in
      hospital mortality between patients managed with or without a PAC (68% [346 of
      506] vs 66% [333 of 507], p=0.39; adjusted hazard ratio 1.09, 95% CI 0.94-1.27).
      We noted complications associated with insertion of a PAC in 46 of 486
      individuals in whom the device was placed, none of which was fatal.
      INTERPRETATION: Our findings indicate no clear evidence of benefit or harm by
      managing critically ill patients with a PAC. Efficacy studies are needed to
      ascertain whether management protocols involving PAC use can result in improved
      outcomes in specific groups if these devices are not to become a redundant
      technology.

PMID- 16084256
TI  - Local understandings of vulnerability and protection during the neonatal period
      in Sylhet District, Bangladesh: a qualitative study.
AB  - BACKGROUND: Understanding of local knowledge and practices relating to the
      newborn period, as locally defined, is needed in the development of interventions
      to reduce neonatal mortality. We describe the organisation of the neonatal period
      in Sylhet District, Bangladesh, the perceived threats to the well-being of
      neonates, and the ways in which families seek to protect them. METHODS: We did 39
      in-depth, unstructured, qualitative interviews with mothers, fathers, and
      grandmothers of neonates, and traditional birth attendants. Data on neonatal
      knowledge and practices were also obtained from a household survey of 6050 women
      who had recently given birth. FINDINGS: Interviewees defined the neonatal period
      as the first 40 days of life (chollish din). Confinement of the mother and baby
      is most strongly observed before the noai ceremony on day 7 or 9, and involves
      restriction of movement outside the home, sleeping where the birth took place
      rather than in the mother's bedroom, and sleeping on a mat on the floor. Newborns
      are seen as vulnerable to cold air, cold food or drinks (either directly or
      indirectly through the mother), and to malevolent spirits or evil eye. Bathing,
      skin care, confinement, and dietary practices all aim to reduce exposure to cold,
      but some of these practices might increase the risk of hypothermia.
      INTERPRETATION: Although fatalism and cultural acceptance of high mortality have
      been cited as reasons for high levels of neonatal mortality, Sylheti families
      seek to protect newborns in several ways. These actions reflect a set of
      assumptions about the newborn period that differ from those of neonatal health
      specialists, and have implications for the design of interventions for neonatal
      care.

PMID- 16084257
TI  - Detection of arsenical drug resistance in Trypanosoma brucei with a simple
      fluorescence test.
AB  - The resurgence of human African trypanosomiasis (HAT), coupled with an increased
      incidence of drug resistance, is of concern. We report a quick, simple, and
      sensitive test for identification of parasites resistant to melarsoprol, the main
      drug used to treat late stage HAT. Resistant parasites are defective in a plasma
      membrane transporter responsible for drug uptake. The same transporter carries
      the fluorescent diamidine DB99 (2,5-bis-(4-amidinophenyl)-3,4-dimethylfuran) into
      trypanosomes. The two DNA-containing structures in the trypanosome--the nucleus
      and the kinetoplast--begin to fluoresce within 1 min of introduction of DB99,
      unless drug resistant.

PMID- 16084258
TI  - Antituberculosis drug resistance and anonymous HIV surveillance in tuberculosis
      patients in Botswana, 2002.
AB  - Two surveys undertaken in Botswana in the 1990s have recorded low rates of
      antituberculosis drug resistance, despite a three-fold rise in tuberculosis since
      1989. We undertook a third survey to determine both trends since 1995 and HIV
      prevalence in tuberculosis patients in Botswana. Sputum specimens were obtained
      from patients nationwide in 2002 who also underwent anonymous, rapid HIV testing
      by use of Oraquick. Of 2200 sputum smear-positive patients and 219 previously
      treated patients with suspected recurrent tuberculosis, 1457 (60%) were infected
      with HIV. Resistance to at least one drug in new patients rose from 16 (3.7%)
      isolates in 1995 to 123 (10.4%; p<0.0001) in 2002. Interventions for tuberculosis
      control are urgently needed in Botswana to prevent further emergence of drug
      resistance.

PMID- 16084259
TI  - Endometrial cancer.
AB  - Each year, endometrial cancer develops in about 142,000 women worldwide, and an
      estimated 42,000 women die from this cancer. The typical age-incidence curve for
      endometrial cancer shows that most cases are diagnosed after the menopause, with
      the highest incidence around the seventh decade of life. The appearance of
      symptoms early in the course explains why most women with endometrial cancer have
      early-stage disease at presentation. For all stages taken together, the overall 5
      year survival is around 80%. There is a substantial prognostic difference between
      the histological types of endometrial cancers. The most common lesions (type 1)
      are typically hormone sensitive and low stage and have an excellent prognosis,
      whereas tumours of type 2 are high grade with a tendency to recur, even in early
      stage. The cornerstone of treatment for endometrial cancer is surgery, which not
      only is important for staging purposes but also enables appropriate tailoring of
      adjuvant treatment modalities that benefit high-risk patients only. We review
      current concepts about epidemiology, pathology, pathogenesis, risk factors and
      prevention, diagnosis, staging, prognostic factors, treatment, and follow-up of
      endometrial cancer.

PMID- 16084260
TI  - Sir James Paget's research into medical education.

PMID- 16084261
TI  - Gates's grandest challenge: transcending technology as public health ideology.

PMID- 16084262
TI  - An unusual case of growth retardation.

PMID- 16084263
TI  - Inhibition of foodborne bacteria by native and modified protamine: importance of
      electrostatic interactions.
AB  - Protamine is a naturally occurring cationic antimicrobial peptide (CAP) that has
      shown some promise for control of microorganisms in food. It was hypothesized
      that the antibacterial effect is partially due to protamine's electrostatic
      affinity to the negatively charged cell envelopes of actively growing bacteria.
      However, nonspecific binding of the CAPs to negatively charged food particles may
      reduce the effect in food systems. To test the hypothesis, the antibacterial
      efficacies of native and reduced charge protamines (chemically modified by
      randomly blocking 10 to 71% of the guanido groups of the arginine residues) were
      compared in model and food systems. In Tryptic Soy Broth, moderate reductions of
      charge (<26%) resulted in either a similar or slightly improved antimicrobial
      efficacy, measured as the minimum inhibitory concentration (MIC) toward 21 food
      related bacteria. Further reductions in positive charge led to lower
      antimicrobial activity. Compared to protamine, the affinity of reduced charge
      protamines (10 and 20%) for binding to Listeria monocytogenes cells was higher at
      pH 7 and 8. As perhaps would be expected, L. monocytogenes is most sensitive to
      modified protamines in this pH range. Protamine with reduced charge (14 and 23%)
      inhibited growth of L. monocytogenes in milk as well as total bacteria and
      coliforms in ground beef significantly (P<0.05) better than native protamine,
      demonstrating that the reduced charge peptides were more inhibitory in these high
      protein food matrices. Electrophoretic analysis of the 21 bacteria revealed a
      statistically significant (P<0.01) relationship with antimicrobial activity,
      where the most negatively charged bacteria were also the most susceptible to
      protamine. In conclusion, components of food matrices interfered with the
      antibacterial effects of the peptides, however; these undesirable interferences
      were reduced by altering the electrostatic properties of protamine.

PMID- 16084264
TI  - Dose response modelling of Escherichia coli O157 incorporating data from
      foodborne and environmental outbreaks.
AB  - A human dose response model for Escherichia coli O157 would enable prediction of
      risk of infection to humans following exposure from either foodborne or
      environmental pathways. However, due to the severe nature of the disease,
      volunteer human dose response studies cannot be carried out. Surrogate models
      from Shigella fed to humans and E. coli O157 to rabbits have been utilised but
      are significantly different to one another. In addition data obtained by animal
      exposure may not be representative for human beings. An alternative approach to
      generating and validating a dose response model is to use quantitative data
      obtained from actual human outbreaks. This work collates outbreak data obtained
      from global sources and these are fitted using exponential and beta-Poisson
      models. The best fitting model was found to be the beta-Poisson model using a
      beta-binomial likelihood and the authors favour the exact version of this model.
      The confidence levels in this model encompass a previously published Shigella
      dose response model. The potential incorporation of this model into QMRAs is
      discussed together with applications of the model to help explain foodborne
      outbreaks.

PMID- 16084265
TI  - Analysis of yeast population during spontaneous alcoholic fermentation: effect of
      the age of the cellar and the practice of inoculation.
AB  - An ecological study of spontaneous fermentation in red wine carried out in two
      wineries located in the same village of the D.O.Ca. Rioja appellation (Spain).
      These two wineries were very different: one was very old and the other commenced
      its operations with the 2000 vintage. The study was conducted over seven
      consecutive years (1997-2003); the first 3 years in the old winery; and the other
      4 years in the new one. Another difference between the wineries was the use of
      commercial strains: no starters were ever used in the old winery and two known
      strains (A and B) were employed only in a white must vat in the new winery. The
      number of different Saccharomyces cerevisiae strains detected for each vintage
      and the frequency of their appearance varied between the old winery and the new
      winery. There was no one clearly dominant clone in the fermentations studied in
      the old winery, whereas in the vinifications monitored in the new winery, a clear
      majority strain was detected. The same S. cerevisiae clone took over the
      spontaneous fermentation of all the vintages studied in this new winery. Analysis
      of the mtDNA restriction pattern of this strain revealed that it was identical to
      one of the commercial strain used (starter A), despite the fact that the
      fermentation studied was spontaneous. Microbial analysis conducted on winery
      equipment and winery surfaces prior to the 2003 vintage revealed that starter A
      had become a resident of the winery with a percentage of 50% among all S.
      cerevisiae. The presence of non-Saccharomyces yeasts in the early stages of
      vinification also differed between the old and new wineries.

PMID- 16084266
TI  - Over-production of the major exoglucanase of Saccharomyces cerevisiae leads to an
      increase in the aroma of wine.
AB  - A Saccharomyces cerevisiae wine strain over-producing an endogenous exoglucanase
      encoded by the EXG1 gene has been constructed to investigate the possible role of
      this enzyme in increasing wine aroma through the release of a glycosidic
      precursor. Purification and biochemical characterization of the EXG1 protein has
      been performed revealing an apparent molecular mass of 61 kDa and an optimal pH
      and temperature of 4-5 and 55 degrees C, respectively. No activity loss due to
      ethanol, SO2, glucose or fructose at concentrations typically found in wine and
      must has been detected. The production of exoglucanase activity by two wine yeast
      strain transformants in which the expression of EXG1 was driven by either the S.
      cerevisiae actin or EXG1 gene promoters has been monitored in culture medium and
      in grape must during the fermentation process. Various alcohols and terpenes were
      enhanced in the aroma profiles of wines produced by inoculation with the
      exoglucanase over-expressing yeasts, though the transformant strain carrying EXG1
      under the control of the actin promoter yielded higher levels of free volatiles
      in wine.

PMID- 16084267
TI  - Influence of controlled lactic fermentation on growth and sporulation of Bacillus
      cereus in milk.
AB  - The growth and sporulation of Bacillus cereus NVH 45 in a fermentor with
      controlled pH or simulated pH conditions were investigated. The study was carried
      out in a fermentor to measure the influence of a rapid and a slow lactic acid
      production on the inhibition of B. cereus in a controlled environment during the
      initial part of fermentation and to observe if other factors than lactic acid
      influenced the inhibition. In the controlled pH experiments the pH was allowed to
      decrease to an end pH 5.0, 5.5 or 6.0 either by Lactobacillus casei 2756 (a fast
      acid producer) or Lactobacillus acidophilus NCFB 1748 (a slow acid producer). In
      co-cultures of Lb. casei 2756 and B. cereus NVH 45, low numbers (10-70 cfu/ml) of
      B. cereus NVH 45 were observed at end pH 5.5 (72 h) while at pH 5.0 no viable
      cells (<10 cfu/ml) were detected (48-72 h). B. cereus NVH 45 did not sporulate in
      co-culture with Lb. casei 2756. In co-culture with Lb. acidophilus NCFB 1748, B.
      cereus NVH 45 sporulated and survived as spores. In these co-cultures B. cereus
      NVH 45 grew to higher maximum counts (>10(7) cfu/ml) than with Lb. casei 2756
      (<10(7) cfu/ml). Significantly different amounts of lactic acid were observed
      between the two co-cultures after 7 and 12 h. A rapid decrease of pH appears to
      prevent B. cereus from sporulating and it seems that it is enough to just reach
      pH 5.0 rapidly and keep that pH to achieve the desirable inhibition of B. cereus.
      In the simulated pH experiments B. cereus NVH 45 was inoculated in the fermentor
      and the different pH developments from different LAB strains were monitored by
      addition of lactic acid. These experiments showed the same tendency: a fast pH
      reduction during the initial hours of fermentation, simulating lactococci,
      resulted in complete inhibition of B. cereus NVH 45 (<10 cfu/ml). However, when
      simulating the pH development of the two different Lactobacillus strains,
      complete inhibition of B. cereus NVH 45 was not seen. In co-cultures competition
      for nutrients with consequences for cell density appears to be important. Based
      on these results it seems that B. cereus must reach a certain density to induce
      sporulation.

PMID- 16084268
TI  - Intense light pulses decontamination of minimally processed vegetables and their
      shelf-life.
AB  - Intense light pulses (ILP) is a new method intended for decontamination of food
      surfaces by killing microorganisms using short time high frequency pulses of an
      intense broad spectrum, rich in UV-C light. This work studied in a first step the
      effect of food components on the killing efficiency of ILP. In a second step, the
      decontamination of eight minimally processed (MP) vegetables by ILP was
      evaluated, and thirdly, the effect of this treatment on the shelf-life of MP
      cabbage and lettuce stored at 7 degrees C in equilibrium modified atmosphere
      packages was assessed by monitoring headspace gas concentrations, microbial
      populations and sensory attributes. Proteins and oil decreased the
      decontamination effect of ILP, whilst carbohydrates and water showed variable
      results depending on the microorganism. For this reason, high protein and fat
      containing food products have little potential to be efficiently treated by ILP.
      Vegetables, on the other hand, do not contain high concentrations of both
      compounds and could therefore be suitable for ILP treatment. For the eight tested
      MP vegetables, log reductions up to 2.04 were achieved on aerobic mesophilic
      counts. For the shelf-life studies, respiration rates at 3% O2 and 7 degrees C
      were 14.63, 17.89, 9.17 and 16.83 ml O2/h kg produce for control and treated
      cabbage, and control and treated lettuce respectively; used packaging
      configurations prevented anoxic conditions during the storage times. Log
      reductions of 0.54 and 0.46 for aerobic psychrothrophic count (APC) were achieved
      after flashing MP cabbage and lettuce respectively. APC of treated cabbage became
      equal than that from control at day 2, and higher at day 7, when the tolerance
      limit (8 log) was reached and the panel detected the presence of unacceptable
      levels of off-odours. Control never reached 8 log in APC and were sensory
      acceptable until the end of the experiment (9 days). In MP lettuce, APC of
      controls reached rejectable levels at day 2, whilst that of treated samples did
      after 3 days. Both samples were sensory unacceptable at day 3, controls because
      of bad overall visual quality (OVQ), off-odour and leaf edge browning and treated
      samples due to bad OVQ; browning inhibitors might be proposed to preserve OVQ.
      Yeasts and lactic acid bacteria counts were low in all the samples. It seems that
      ILP treatment alone under the conditions used in this work does not increase MP
      vegetables shelf-life in spite of the reduction in the initial microbial load.

PMID- 16084269
TI  - Bacterial community structure in kimchi, a Korean fermented vegetable food, as
      revealed by 16S rRNA gene analysis.
AB  - Kimchi is a traditional Korean food fermented from a variety of vegetables. We
      elucidated the microbial community structure of five commercially produced
      kimchis made from Chinese cabbage by examining culture-independent 16S rRNA gene
      clone libraries. Most of the clones (347 out of 348) belonged to lactic acid
      bacteria and included several species of the genera Lactobacillus, Leuconostoc
      and Weissella. Weissella koreensis was found in all the samples and predominated
      in three of them (42.6-82%). Leuconostoc gelidum, Leuconostoc gasicomitatum and
      Lactobacillus sakei were common in the remaining kimchi clone libraries (>34%).
      The composition of bacterial phylotypes in kimchi varied between samples. Our
      approach revealed different community structures from those reported in previous
      culture-dependent studies based on phenotypic identification methods. The culture
      independent method used here proved to be efficient and accurate and showed that
      the bacterial communities in kimchi differ from those in other fermented
      vegetable foods.

PMID- 16084270
TI  - Immunostimulatory probiotic Lactobacillus rhamnosus HN001 and Bifidobacterium
      lactis HN019 do not induce pathological inflammation in mouse model of
      experimental autoimmune thyroiditis.
AB  - The possibility that intestinal microflora contribute to the pathogenesis of
      autoimmune diseases has raised issues regarding the safety of probiotic
      organisms, especially those with immunostimulating properties, in individuals
      with such immune dysfunctions. In this study, the effect of consumption of
      probiotic lactic acid bacteria (LAB) strains Lactobacillus rhamnosus HN001(HN001)
      and Bifidobacterium lactis HN019 (HN019) on the induction and progression of
      experimental autoimmune thyroiditis (EAT) was investigated in CBA/CaH (H-2k)
      mice. HN001 or HN019 in skim milk were fed to mice daily (1-1.5 x 10(8)
      cfu/mouse/day) for 5 to 9 weeks. A mild form of EAT was induced by subcutaneous
      injection of mouse thyroglobulin (MTg) with either Freund's adjuvant (complete
      and incomplete, CFA and IFA) or lipopolysaccharide (LPS). The proliferative
      responses of spleen lymphocyte to MTg stimulation in vitro and the presence (and
      degree) of mononuclear cell infiltration in thyroid gland tissues were examined
      to assess the development and severity of EAT. The levels of serum anti-MTg
      antibodies (IgG1 and IgG2a) and spleen weight index were determined to detect the
      presence of autoimmune responses of mice receiving MTg. Results showed that 8
      weeks after immunization, 16.67-50% of the mice developed mild EAT with
      lymphocyte infiltration in the thyroid glands. Probiotic feeding did not induce
      full-blown EAT. There were no differences in spleen weight index or the
      proliferative spleenocytes in response to PMA between mice that received MTg
      alone and mice that received MTg and probiotic LAB strains.

PMID- 16084274
TI  - Management of peripheral arterial disease in chronic kidney disease.
AB  - PAD has been overlooked in many epidemiologic studies evaluating cardiovascular
      risk associated with renal disease. Conversely, CKD has not been evaluated as a
      potential risk factor in epidemiologic studies of PAD. PAD, however,seems to be
      more prevalent among patients with even moderate CKD than in the general
      population and is most common among chronic dialysis patients, one third or more
      of whom have a low ABI. Patients with CKD also seem to be at increased risk for
      developing claudication and for requiring surgical intervention for lower
      extremity PAD. Furthermore, even moderate CKD seems to be a risk factor for
      postoperative death and complications after both lower extremity amputation and
      revascularization procedures. Conversely, even asymptomatic PAD seems to be a
      risk factor for death among dialysis patients. In the general population,
      statins, antiplatelet agents (particularly clopidogrel), antihypertensive agents,
      and ACE inhibitors all have a proven benefit in reducing cardiovascular events in
      patients with PAD and in some instances may also reduce PAD events. Available
      evidence suggests that patients with CKD also experience cardio-vascular risk
      reduction with statin and ACE-inhibitor therapy, but these therapies have not
      been shown to reduce PAD events specifically in patients with CKD. Further
      studies are needed to identify interventions that can specifically reduce the
      incidence of PAD complications in patientswith CKD. Although it is clear that
      mortality and complication rates after both lower extremity amputation and
      revascularization are increased in patients with even moderate CKD, currently
      available observational studies do not provide clear guidance for surgical
      decision making in CKD patients with limb-threatening ischemia. Further studies
      are needed to evaluate the risksand benefits of amputation over
      revascularizationamong patients with CKD and to investigatereasons for the high
      mortality associated with these procedures in this patient group. Further studies
      are also needed to measure the impact of CKD on care processes for PAD with the
      goal of identifying target areas for improvement.

PMID- 16084275
TI  - Hypertension in chronic kidney disease and dialysis: pathophysiology and
      management.
AB  - Hypertension affects 24% of the adult US population. In the United States, 3% of
      the adult population has an elevated serum creatinine level, and 70% of these
      patients have hypertension. The prevalence of hypertension in chronic kidney
      disease (CKD) depends on the patient's age and the severity of renal failure,
      proteinuria, and underlying renal disease. As patients with CKD progress to end
      stage renal disease (ESRD), 86% are diagnosed with hypertension. It has long been
      recognized that kidney function affects and is affected by hypertension. This
      article discusses the pathophysiology and management of hypertension in patients
      with CKD.

PMID- 16084276
TI  - Vascular access in hemodialysis: issues, management, and emerging concepts.
AB  - This article (1) identifies the types of hemodialysis access, (2) summarizes the
      clinical standard of care for dialysis access grafts and fistulae, (3) describes
      the pathology and pathogenesis of venous stenosis in dialysis access grafts and
      fistulae, (4) tabulates avail-able therapies for hemodialysis vascular access
      dysfunction and speculates on the rea-sons for the lack of effective therapies,
      and (5) discusses the development and application of novel therapeutic
      interventions for this difficult clinical problem. The possibility that dialysis
      access grafts and fistulae could be the ideal clinical model for testing novel
      local therapies to block neointimal hyperplasia is discussed.

PMID- 16084277
TI  - Congestive heart failure in chronic kidney disease: disease-specific mechanisms
      of systolic and diastolic heart failure and management.
AB  - There is a high burden of cardiac disease in the CKD population. Severe LVH,
      dilated cardiomyopathy, and coronary artery disease occur frequently and result
      in the manifestations of CHF,which is probably more important with respect to
      prognosis than symptomatic. Multiple risk factors for CVD include traditional
      risk factors and those unique to the CKD population. Furthermore, the distinctive
      aspects of CKD patients sometimes warrant special consideration in making
      management decisions. Nonetheless, interventions such as controlling
      hypertension, specific pharmacologic options, lifestyle modification, anemia
      management, and early nephrology referral are recommended when appropriate.

PMID- 16084278
TI  - Coronary artery disease and peripheral vascular disease in chronic kidney
      disease: an epidemiological perspective.
AB  - The enormous burden of CAD and PVD inpatients who have CKD contributes
      substantially to increased morbidity and mortality. The increased risk of
      vascular disease observed in CKD patients is likely to be multifactorial, with
      contributions from traditional and nontraditional cardiovascular factors. Given
      the overwhelming evidence on the known benefits of cardioprotective medications,
      their underuse remains puzzling in a population at enormous risk. During the past
      5 years, the research community and national interest groups have made
      significant progress in organizing a concerted approach to improve the management
      of patients who have CKD and vascular disease. Much work remains to be done. The
      development of national guidelines in the management of these patients at high
      risk for future cardiovascular events will be a welcome step. The evaluation of
      multitargeted interventions for reduction of cardiovascular risk through
      randomized clinical trials is desperately needed. Finally, the low use of known
      cardioprotective strategies in this high-risk group is a serious issue and
      warrants immediate attention at local and national levels.

PMID- 16084279
TI  - Percutaneous coronary interventions in the high-risk renal patient: strategies
      for renal protection and vascular protection.
AB  - CKD is the most important factor in predict-ing adverse short- and long-term
      outcomes after PCI. Hence, the rationale for renal end-organ protection is based
      on chronic renal protection,avoidance of additive renal insults, and a
      comprehensive CIN prophylaxis. The pathogenesis of CIN goes beyond serum
      creatinine and involves a unique vascular pathobiology in which interrelates
      renal and CVD outcomes are interrelated. Attempts at PCI in patients with CKD and
      ESRD are high-risk procedures, but the risks involved seem to be warranted given
      comparative outcomes in conservatively treated patients. The benefits of short-
      and long-term vascular protective therapies in CKD patients have been confirmed,
      and these therapies are an important component of PCI care.

PMID- 16084280
TI  - Pathophysiology of cardiovascular disease and renal failure.
AB  - This article discusses the epidemiology of cardiovascular (CV) events in end
      stage and early renal disease, summarizes the profile of classic and nonclassic
      CV risk factors in renal patients, highlights recent evidence documenting
      accelerated atherogenesis in renal disease, and provides information on the
      central arteries and heart as target organs for CV damage in renal disease.

PMID- 16084281
TI  - Relevance of oxidative pathways in the pathophysiology of chronic kidney disease.
AB  - Patients with uremia (whether requiring renal replacement therapy or not) have a
      greatly increased cardiovascular risk that cannot be explained entirely by
      traditional cardiovascular risk factors. An increase in oxidative stress has been
      proposed as a nontraditional cardiovascular risk factor in this patient
      population. Using a wide variety of different biomarkers of increased oxidative
      stress status, numerous laboratories around the world have now unequivocally
      demonstrated that uremia is a state of increased oxidative stress. Recent data
      also suggest linkages between oxidative stress inflammation, endothelial
      dysfunction, and malnutrition in the uremic population. These factors are
      probably synergistic in their effects on atherogenecity and risk of a
      cardiovascular event. The pathophysiology of increased oxidative stress in uremia
      is multifactorial, but the retention of oxidized solute by the loss of kidney
      function is probably a major contributor. Uremic oxidative stress can be
      characterized biologically by an increase in lipid per oxidation products and
      reactive aldehyde groups as well as by increased retention of oxidized thiols.
      Two recently published studies have suggested that antioxidative therapy may be
      particularly promising in reducing cardiovascular events in this patient
      population.Further definitive studies of antioxidant use are greatly needed.

PMID- 16084282
TI  - Management of cardiovascular disease in the renal transplant recipient.
AB  - RTRs are at high risk for ischemic heart disease and heart failure. Although some
      differences pertain, most of the major risk factors are similar to those in the
      general population. It is highly probable that interventions of proven benefit in
      the general population will also be of benefit in RTRs. A combination of
      lifestyle modifications (smoking cessation, maintenance of ideal bodyweight,
      healthy diet), aggressive blood pressure control (<130/80 mm Hg), use of ACE
      inhibitors or ARBs, lipid lowering with statins, antiplatelet therapy for
      diabetics and those with established coronary disease, and beta blockers for CHF
      or after myocardial infarction is likely to have a major benefit on patient
      survival and cardiac morbidity among transplant recipients. Coronary
      revascularization should be considered for the same indications as in the general
      population.

PMID- 16084283
TI  - Chronic kidney disease: a risk factor for cardiovascular disease.
AB  - The goal of risk stratification of CVD inpatients with CKD is to lead to
      effective and early intervention and to prevent the adverse outcomes associated
      with this complex multisystem disease that is characteristic of growing number of
      patients with CKD in the general population and of patients receiving dialysis
      therapy or kidney transplantation. By 2030, there will be 2.24 million patients
      with ESRD in the United States, and approximately 1.3 million of these cases of
      ESRD will be caused by diabetes mellitus. Thus, CVD in this high-risk population
      presents a challenge for the nephrology and the cardiology community.

PMID- 16084284
TI  - Kidney disease and cardiovascular disease: implications of dyslipidemia.
AB  - Cardiovascular complications are common inpatients with kidney disease.
      Regulating the lipid levels in these patients is important so that the risks of
      kidney and cardiovascular complications can be minimized. Lipid regulation
      decreases the incidence of coronary vascular events and other vascular
      complications in patients with kidney disease; however, whether lipid regulation
      slows progression of kidney disease is not yet known. Additional studies of the
      implications of dyslipidemia in patients with kidney disease are needed.

PMID- 16084285
TI  - Vascular calcification in patients with renal failure: culprit or innocent
      bystander?
AB  - The mortality from cardiovascular events in CKD and dialysis patients is
      substantially higher than in the general population. VC is ubiquitous and
      progresses rapidly in this patient population. Although there has been progress
      in the understanding of the pathogenesis and correlates of VC, much work needs to
      be done in this area. The role of calcium and, probably, phosphate (obligatory
      participants) is unquestionable, but the understanding of the paracrine and
      molecular determinants of VC in renal failure is continuously evolving. VC is
      probably a dynamic process resulting from the imbalance between molecules that
      promote and those that inhibit VC. The understanding of latter area has recently
      evolved with identification of new signaling pathways with molecules such as
      osteoprotegerin, fetuin-A, and MPG. From a clinical perspective, new modalities
      such as EBCT and MDCT allow noninvasive detection and quantification of VC. VC
      may represent a potential useful index for prognostic stratification and
      treatment planning in patients who have renal failure. At present, however, the
      data on the prognostic value of VC are available only in populations of patients
      who have normal renal function. Large-scale, prospective, observational studies
      should be designed to identify the determinants of VC and to define the
      prognostic role of calcium scoring in cohorts of patients who have predialysis
      CKD and with ESRD.

PMID- 16084286
TI  - Newer paradigms in renal replacement therapy: will they alter cardiovascular
      outcomes?
AB  - Cardiovascular disease remains the leading cause of morbidity and mortality for
      patients with end-stage renal disease. Conventional hemodialysis has had limited
      impact on cardiovascular risk factors and mortality. Increasing evidence suggests
      that nocturnal home hemodialysis has beneficial effects on cardiovascular
      parameter outcomes. This article reviews the documented effects of nocturnal home
      hemodialysis on blood pressure control, cardiac geometry and left ventricular
      systolic function, lipid profiles, calcium-phosphate metabolism, parathyroid
      hormone levels, homocysteine levels, sleep apnea, and autonomic modulation of
      heart rate. It discusses possible mechanisms to explain these observed changes.

PMID- 16084287
TI  - Soft-tissue interference fixation: bioabsorbable screw versus metal screw.
AB  - PURPOSE: To compare the biomechanical properties of eccentrically positioned
      bioabsorbable and titanium interference screws for quadrupled hamstring tendon
      graft (QHTG) fixation. TYPE OF STUDY: In vitro, biomechanical study. METHODS: In
      10 paired cadaveric tibiae and femurs (mean age, 66.5 years; range, 53 to 81
      years), QHTG fixation was performed in tunnels sized to within 0.5 mm of QHTG
      diameter using either a titanium (RCI; Smith & Nephew Donjoy, Carlsbad, CA) or a
      bioabsorbable (BioScrew; Linvatec, Largo, FL) screw of equal size. Constructs
      then underwent biomechanical load-to-failure testing on a servo-hydraulic device
      at 20 mm/min. RESULTS: Load at failure was greater for femoral-side QHTG fixation
      using the bioabsorbable screw than the titanium screw (486 +/- 223.7 N v 246 +/-
      99.1 N, P = .006); however, displacement did not differ (P = .81). There were no
      statistically significant differences between groups for tibial side load at
      failure (P = .54), stiffness (P = .44), or displacement (P = .50). Screw thread
      induced graft laceration was more frequently observed in the titanium screw group
      (9 of 10 grafts during femoral-side testing, 0 of 10 grafts during tibial-side
      testing) than in the bioabsorbable screw group (0 of 10 grafts during femoral
      side testing, 1 of 10 grafts during tibial-side testing). CONCLUSIONS: BioScrew
      interference screw fixation was comparable or superior to RCI titanium
      interference screw fixation. BioScrew interference screw fixation also produced
      less screw thread-induced laceration of the QHTG during load-to-failure testing.
      CLINICAL RELEVANCE: Use of a biodegradable interference screw positioned directly
      against a soft-tissue graft provides fixation properties similar to those of a
      metal interference screw.

PMID- 16084288
TI  - Changes in cross-sectional area of hamstring anterior cruciate ligament grafts as
      a function of time following transplantation.
AB  - PURPOSE: To measure the cross-sectional area (CSA) of hamstring anterior cruciate
      ligament (ACL) grafts in humans up to 2 years postoperatively and to estimate the
      appropriate graft-notch distance (the distance between ACL graft and roof or wall
      of the notch) at surgery. TYPE OF STUDY: Case series. METHODS: Fifty-nine
      patients, who had consented to have a magnetic resonance imaging (MRI) evaluation
      postoperatively, underwent endoscopic ACL reconstruction using 3- to 5-strand
      autogenous hamstring tendons. Intraoperatively, the CSA of the graft was measured
      using a custom-made area micrometer. Postoperatively, 115 axial MRIs of the
      grafts (48 at 3 months, 44 at 12 months, and 23 at 24 months) were obtained. They
      were transmitted to a personal computer and the CSAs of the grafts' midsubstance
      were calculated. To evaluate the accuracy of the MRI measurement, another 15
      patients who consented to have MRI 2 days after surgery were selected and
      intraoperative graft CSA measurements and graft axial MRI were performed 2 days
      after surgery. RESULTS: The CSAs of the grafts measured by MRI 2 days after
      surgery were well correlated with those directly measured intraoperatively (gamma
      = 0.905). The CSA of the grafts measured intraoperatively was 43 +/- 5 mm2, and
      those estimated by MRI at 3, 12, and 24 months were 50 +/- 9 mm2, 54 +/- 9 mm2,
      and 48 +/- 12 mm2, respectively. The increase in graft diameter at 3, 12, and 24
      months was 9% +/- 8%, 13% +/- 10%, and 7% +/- 12%, respectively. CONCLUSIONS: In
      humans, the increase in CSA of the ACL graft was smaller compared with previous
      animal studies. The graft CSA increased up to 29% (13% in diameter) 12 months
      after surgery. When a 95% confidence interval was used, the percent increase in
      diameter of the reconstructed graft was estimated to be less than 32% in 95% of
      the cases. When the graft diameter was 7, 8, or 9 mm, a 1.1-, 1.3-, or 1.4-mm
      graft-notch distance, respectively, was suitable for impingement-free graft
      during postoperative periods with 95% of probability. LEVEL OF EVIDENCE: Level
      IIII.

PMID- 16084289
TI  - The impact of radiofrequency shrinkage on the mechanical and histologic
      properties of the elongated anterior cruciate ligament in a sheep model.
AB  - PURPOSE: Shrinkage of the elongated anterior cruciate ligament (ACL) and its
      grafts with radiofrequency (RF) energy has become increasingly popular as an
      alternative to ACL reconstruction in the field of knee surgery. Although there
      have been a few clinical studies on the outcome and complications of RF shrinkage
      of the elongated ACL, there is a substantial lack of in vivo basic science
      studies to evaluate the mechanical and histologic changes of such treated tissue.
      Therefore, it was the aim of this study to simulate an ACL elongation in an
      animal model, treat this pathology with RF shrinkage, and analyze the mechanical
      and histologic changes at 6 months after initial treatment. TYPE OF STUDY:
      Experimental in vivo animal study. METHODS: A chronic elongation of the ACL was
      simulated in 16 mature female merino sheep. In group A, no treatment was applied;
      in group B, RF shrinkage was used. For biomechanical testing anteroposterior (AP)
      laxity was measured at time zero and 24 weeks. A load-to-failure test was also
      performed at 24 weeks. For histologic analysis, cell number and crimp pattern
      were measured by conventional histologic examination and the vascular status by
      immunohistochemical histologic examination. RESULTS: The initial reduction of AP
      laxity after RF shrinkage could not be maintained at 24 weeks. A significant
      reduction in ultimate load was found at 24 weeks in the RF-treated group B
      compared with the untreated group A. At 24 weeks, an intensive process of tendon
      remodeling was ongoing in the RF-treated group that differed substantially from
      the untreated elongated ACLs and the intact ACL. CONCLUSIONS: The treatment of an
      elongated ACL with RF energy resulted in a significant impairment of its ultimate
      load and induced a process of intensive remodeling that was not completed at 24
      weeks. Therefore, strong caution is warranted during the time of rehabilitation,
      considering the impaired ligamentous structure. CLINICAL RELEVANCE: This study
      provides insights into the consequences of RF shrinkage of the ACL that will
      guide the clinician in the appropriate rehabilitation of patients and informs of
      possible complications associated with this procedure.

PMID- 16084290
TI  - Cyclic loading comparison between biodegradable interference screw fixation and
      biodegradable double cross-pin fixation of human bone-patellar tendon-bone
      grafts.
AB  - PURPOSE: The aim of this study was to compare ultimate load, yield load,
      stiffness, and displacement after cyclic loading of a cross-pin technique and an
      interference screw technique for the fixation of bone-patellar tendon-bone (BPTB)
      grafts in anterior cruciate ligament (ACL) reconstruction. TYPE OF STUDY:
      Biomechanical in vitro study. METHODS: The devices tested were 2 2.7-mm
      biodegradable pins (RigidFix; Ethicon, Mitek Division, Norderstedt, Germany) and
      biodegradable interference screws (Absolute; Innovasive Devices, Marlborough,
      MA). Each device was used for the fixation of 10 8-mm, 9-mm, or 10-mm sized human
      BPTB grafts in tunnels drilled in bovine knees. Ultimate load, yield load,
      stiffness, and displacement after cyclic loading (1,000 cycles between 50 and 250
      N) were then evaluated. RESULTS: All 8-mm grafts that were fixed with cross-pins
      failed after a mean of 124 cycles of load. The 9-mm and 10-mm grafts survived the
      cyclic loading protocol. Yield load and maximum load of the 10-mm groups (cross
      pin and interference screw) were significantly higher than that of the 9-mm
      groups. There was no significant difference in maximum load, yield load, and
      stiffness between the cross-pin and interference screw fixation technique for 1
      graft size. CONCLUSIONS: The biomechanical data suggest that femoral fixation of
      9-mm and 10-mm BPTB grafts using 2.7-mm biodegradable cross-pins leads to primary
      stability that is comparable to that of biodegradable interference screws.
      Fixation of 8-mm BPTB grafts using 2.7-mm biodegradable cross-pins had poor
      results. CLINICAL RELEVANCE: The diameter of the bone block is the limiting
      factor for the final fixation strength and the cyclical survival when using cross
      pins. We strongly recommend not using this technique for bone blocks smaller than
      9 mm in diameter.

PMID- 16084291
TI  - Intersurgeon variance in computer-assisted planning of anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: To test the hypothesis that computer-controlled virtual planning will
      prohibit tunnel malpositioning and minimize variance in tunnel placement in
      anterior cruciate ligament (ACL) reconstruction, thereby providing us with a more
      accurate and reproducible procedure. TYPE OF STUDY: In vitro cadaver study.
      METHODS: Three orthopaedic surgeons with different levels of experience in ACL
      reconstruction were asked to position tunnel placement K-wires in a predefined
      "optimal" position using both computer-assisted surgery (CAS) and conventional
      techniques in 12 fresh-frozen cadaver knees. Virtual cylindrical 8-mm grafts were
      virtualized as the computer system outlined an impingement area and visualized
      graft elongation. CAS positioning and conventional techniques were compared
      between surgeons and correlated to experience level. RESULTS: The difference in
      virtual planning was 5.02 mm (SD, 2.40; range, 1.77 to 9.64 mm) between the
      tibial tunnels and 4.61 mm (SD, 2.13; range, 2.06 to 8.42 mm) between the femoral
      tunnels. The mean difference between the CAS and conventional procedures was 6.20
      mm (SD, 2.49; range, 3.00 to 10.39 mm) for the femoral tunnel and 6.46 mm (SD,
      2.27; range, 2.65 to 10.47 mm) for the tibia tunnel. The 2 less-experienced
      surgeons were responsible for 3 cases of impingement when using a conventional
      procedure. No elongation or impingement was seen when using CAS. CONCLUSIONS:
      This cadaver study shows that computer assisted planning may reduce intersurgical
      variance. CLINICAL RELEVANCE: Computer navigation and virtual ligament
      reconstruction constitute a good arthroscopic surgery teaching tool. This
      technique enables residents and less experienced surgeons to control positioning
      and limit complications caused by tunnel misplacement.

PMID- 16084292
TI  - Incidence and risk factors for graft rupture and contralateral rupture after
      anterior cruciate ligament reconstruction.
AB  - PURPOSE: The aim of this study was to determine the rates of contralateral
      anterior cruciate ligament (ACL) rupture and of ACL graft rupture after ACL
      reconstruction using either patellar tendon or hamstring tendon autograft, and to
      identify any patient characteristics that may increase this risk. TYPE OF STUDY:
      Case series. METHODS: Over a 2-year period, 760 endoscopic ACL reconstructions
      were performed in 743 patients. Bone-patellar tendon-bone autograft was used in
      316 patients and 4-strand hamstring tendon in 427 patients. Those patients with a
      previous contralateral ACL rupture or those who underwent a simultaneous
      bilateral ACL reconstruction were excluded, leaving 675 knees (675 patients) for
      review. Persons not involved in the index operation or the care of the patient
      conducted follow-up assessment by telephone interview conducted 5 years after
      surgery. Patients were questioned about the incidence of ACL graft rupture,
      contralateral ACL rupture, symptoms of instability or significant injury, family
      history of ACL injury, and activity level according to the International Knee
      Documentation Committee scale. From our prospective database we obtained further
      information on graft source, meniscal or articular surface injury, and gender.
      Binary logistic regression was used to measure the relative association between
      the measured variables and the risk of graft rupture and contralateral ACL
      rupture. RESULTS: Five years after primary ACL reconstruction, 612 of the 675
      patients (90.7%) were assessed. ACL graft rupture occurred in 39 patients (6%)
      and contralateral ACL rupture occurred in 35 patients (6%). Three patients
      suffered both a graft rupture and a contralateral ACL injury. The odds of ACL
      graft rupture were increased 3-fold by a contact mechanism of initial injury.
      Return to level 1 or 2 sports increased the risk of contralateral ACL injury by a
      factor of 10. The risk of sustaining an ACL graft rupture was greatest in the
      first 12 months after reconstruction. No other studied variable increased the
      risk of repeat ACL injury. CONCLUSIONS: After reconstruction, repeat ACL injury
      occurred in 12% of patients over 5 years. Twelve months after reconstruction, the
      ACL graft is at no greater risk than the contralateral ACL, suggesting that
      adequate graft and muscular function for most activities is achieved by this
      time. Risk factors for repeat ACL injury identified included a return to
      competitive side-stepping, pivoting, or jumping sports, and the contact mechanism
      of the index injury. Female patients were at no greater risk of repeat ACL injury
      than male patients and graft choice did not affect the rate of repeat ACL injury.
      LEVEL OF EVIDENCE: Level IV, case series.

PMID- 16084293
TI  - Outcome and risk factors after anterior cruciate ligament reconstruction: a
      follow-up study of 948 patients.
AB  - PURPOSE: The aim of the study was to assess the outcome and risk factors after
      anterior cruciate ligament (ACL) reconstruction in a large group of patients.
      TYPE OF STUDY: Case series. METHODS: Included in this retrospective study were
      948 patients (323 female, 625 male) with a symptomatic unilateral ACL rupture,
      who underwent arthroscopic reconstruction using patellar tendon autograft and
      interference screw fixation at 3 Swedish hospitals. The median age of the
      patients at the time of the index operation was 26 years (range, 14 to 53 years).
      The patients underwent surgery at a median of 12 months (range, 0.5 to 360
      months) after their injury. Independent physiotherapists performed the follow-up
      examinations at a median of 32 months (range, 21 to 117 months) postoperatively.
      RESULTS: Of the 948 patients, 550 (58%) underwent meniscal surgery before,
      during, or after the ACL reconstruction. The median Tegner activity level was 8
      (range, 2-10) before injury, 3 (range, 0-9) preoperatively, and 6 (range, 1-10)
      at follow-up (P < .0001 preoperative v follow-up). At follow-up, the median
      Lysholm score was 90 points (range, 14-100), the median KT-1000 anterior side-to
      side laxity difference was 1.5 mm (range, -6 to 13 mm), and the median 1-leg hop
      test quotient was 95% (0% to 167%) compared with the contralateral normal side.
      At follow-up, 69.3% of the patients were classified as normal or nearly normal
      according to the International Knee Documentation Committee evaluation system.
      However, 36% of the patients were unable to or had severe problems performing the
      knee-walking test. Inferior results correlated with increased time period between
      the index injury and reconstruction and concomitant joint damage found at the
      index operation. CONCLUSIONS: Overall, the results were good after ACL
      reconstruction using patellar tendon autograft and interference screw fixation.
      Concomitant joint damage and a long time period between the injury and
      reconstruction are major risk factors for inferior outcome after ACL
      reconstruction. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 16084294
TI  - Posterior cruciate ligament reconstruction: double-loop hamstring tendon
      autograft versus Achilles tendon allograft--clinical results of a minimum 2-year
      follow-up.
AB  - PURPOSE: The purpose of this study was to compare clinical results of
      arthroscopic posterior cruciate ligament (PCL) reconstructions using double-loop
      hamstring tendon autograft and Achilles tendon allograft while preserving the
      original PCL remnant. TYPE OF STUDY: Case-control study of results of treatment.
      METHODS: From September 1997 to December 2000, 36 patients who received only PCL
      reconstruction were reviewed retrospectively. Of these, 18 patients received
      autogenous double-loop hamstring tendon reconstruction (group I) and 18 received
      Achilles tendon allograft reconstruction (group II). The same PCL reconstruction
      procedure was performed in both groups. At final follow-up at a minimum of 2
      years, patients were evaluated by 4 measures: the International Knee
      Documentation Committee (IKDC) evaluation, Lysholm knee scores, the posterior
      draw test, and Telos stress radiography. RESULTS: Between the 2 groups,
      preoperative demographic factors (age, gender, activity level, and mean duration
      to surgery) showed no statistically significant difference (P > .05). According
      to IKDC evaluation of group I, 16 of the 18 knees rated normal or nearly normal,
      whereas 2 fell into the abnormal category. By the same criteria, 14 of the 18
      knees in group II were normal to nearly normal, 3 were abnormal, and 1 was
      severely abnormal. IKDC scores showed no statistical difference between the 2
      groups (P = .98). Postoperative mean Lysholm knee scores were 90 points (range,
      78-100) for group I and 85 (range, 70-95) for group II; improvements of 22 and 17
      points, respectively. According to the Lysholm knee scores, group I showed
      slightly better results than did group II, with a statistical significance of P <
      .01. Telos stress radiography showed the mean difference in posterior translation
      between the injured and uninjured knees to be 2.2 mm (range, 0 to 7.0 mm) for
      group I and 2.9 mm (range, 1.0 to 7.0 mm) for group II. The Telos stress test
      showed no statistical difference between the 2 groups (P = .14). CONCLUSIONS: The
      clinical outcome was the same for both groups. Despite its comparatively short
      length and small diameter, the double-loop hamstring tendon autograft was as good
      as Achilles tendon allograft in PCL reconstruction. LEVEL OF EVIDENCE: Level III,
      case-control study.

PMID- 16084295
TI  - Primary stability of three posterior cruciate ligament reconstruction procedures:
      a biomechanical in vitro study.
AB  - PURPOSE: Posterior cruciate ligament (PCL) reconstruction procedures have not
      been thoroughly evaluated under cyclic loading conditions. We tested the
      hypothesis that PCL reconstruction with a quadrupled flexor-tendon graft and
      fixation using tapes and staples is biomechanically superior to that fixed with
      sutures, a button, and a post-screw, and is comparable to reconstruction with a
      bone--patellar tendon--bone (BPTB) graft. STUDY DESIGN: In vitro biomechanical
      study. METHODS: A total of 45 porcine knees were used. The quadrupled flexor
      tendon graft was fixed using the suture/button/post-screw procedure in 15 knees,
      and with the tape/staples procedure in another 15 knees. The remaining 15 knees
      underwent reconstruction with a BPTB graft secured with screws as the standard
      control. In each group of 15 knees, 5 underwent tensile testing without cyclic
      loading, and 10 underwent the same tensile test after 5,000 cycles of load
      controlled or displacement-controlled loading. RESULTS: Each type of cyclic
      loading produced larger biomechanical changes in the knees fixed with the
      suture/button/post-screw procedure than in the knees secured using the other 2
      procedures. CONCLUSIONS: In PCL reconstruction, the tape/staples procedure is
      biomechanically superior to the suture/button/post-screw procedure, and is
      comparable to the BPTB/screws procedure with regard to the ultimate failure load.
      Neither of the procedures using the quadrupled flexor-tendon graft was comparable
      to the BPTB graft in linear stiffness and the initial displacement after load
      controlled cyclic testing. CLINICAL RELEVANCE: The biomechanical behaviors of PCL
      reconstructed knees are significantly different, depending on surgical
      techniques.

PMID- 16084296
TI  - Reconciling arthroscopic and anatomic morphology of the humeral insertion of the
      inferior glenohumeral ligament.
AB  - PURPOSE: To clarify the morphology of the humeral insertion of the inferior
      glenohumeral ligament (IGHL). TYPE OF STUDY: Cadaveric and arthroscopic anatomic
      analysis. METHODS: The morphology of the humeral insertion was studied in 200
      nonembalmed cadavers through open dissection (100 specimens), by arthroscopy (50
      specimens), or both (50 specimens). In addition, the morphology was studied in
      100 living subjects with stable shoulders undergoing shoulder arthroscopy.
      RESULTS: On the humeral side, the insertion of the inferior capsular fibers is
      usually in the form of a V, the point of which is covered by the tendon of the
      latissimus dorsi. When viewed intra-articularly, the inferior insertion usually
      gives a collar-like impression because the capsular recess is filled with frenula
      capsulae. CONCLUSIONS: Our description corresponds with that found in the classic
      literature. Our results are, however, in contrast with those of others who have
      observed about 50% of V-shaped insertions. This difference may be explained by
      the method of observation and by the small numbers of specimens studied. The form
      of the humeral insertion of the IGHL is linked to the formation of a supporting
      hammock that can accommodate the humeral head during movement as described by
      several authors. CLINICAL RELEVANCE: We believe that the difference between
      arthroscopic and anatomic observation of the humeral insertion may have 2 major
      clinical implications. An observed tear of the frenula capsulae may not
      necessarily represent a humeral avulsion of the glenohumeral ligaments (HAGL). In
      the case of a HAGL, the capsule may have to be reattached in its V-form to
      adequately retension the inferior capsule.

PMID- 16084297
TI  - Treatment of glenohumeral subluxation using electrothermal capsulorrhaphy.
AB  - PURPOSE: The purpose of this study was to review the results of a relatively
      homogenous group of patients with glenohumeral subluxation without labral
      pathology who were treated with an electrothermal capsulorrhaphy procedure. TYPE
      OF STUDY: Case series without controls. METHODS: From 1997 to 1998, 42 patients
      underwent electrothermal capsulorrhaphy using a monopolar radiofrequency probe
      (Oratec Interventions, Menlo Park, CA). Patients with prior capsular repairs,
      labral pathology that required repair, or capsular avulsion injuries were
      excluded from the study. Thirty-one patients met the inclusion criteria. Patients
      had a minimum of 2 years of follow-up (mean, 25 months), and a mean age of 25
      years (range, 16 to 38 years). All of the patients had previously failed
      conservative treatment. There were 25 patients with unidirectional anterior
      instability, 2 patients with unidirectional inferior instability, 1 patient with
      unidirectional posterior instability, and 3 patients with multidirectional
      instability. The patients were assessed using a modified American Shoulder and
      Elbow Surgeons (ASES) score that examined pain (30 points), function (60 points),
      and patient satisfaction (10 points). In addition, subjective stability was
      assessed using a 10-point scale. RESULTS: The average modified ASES score
      increased to 88 points from 56 preoperatively (P < .01). The average subjective
      stability scale increased to 8.5 from 4.4 preoperatively (P < .01). Nineteen
      patients (61%) had an excellent result, 4 (13%) had a good result, 5 (16%) had a
      fair result, and 3 (10%) had a poor result; 22 of 26 patients who participated in
      sports were able to return to their preinjury level of play. The subset of
      patients with isolated anterior instability had results similar to the overall
      group. There were no instances of axillary neuritis or other neurologic injury.
      CONCLUSIONS: In carefully selected patients with shoulder instability, including
      unidirectional anterior instability without associated labral pathology,
      electrothermal capsulorrhaphy was effective and had few complications. LEVEL OF
      EVIDENCE: Level IV, case series without controls.

PMID- 16084298
TI  - Mechanical strength of four different biceps tenodesis techniques.
AB  - PURPOSE: The aim of this study was to compare the biomechanical properties of 4
      different biceps tenodesis techniques. TYPE OF STUDY: Biomechanical experiment.
      METHODS: Four groups of fresh sheep shoulders (28 total) with similar shape
      characteristics were used. Biceps tenodesis was performed using the following
      techniques: group 1 (n = 7), tunnel technique; group 2 (n = 7), interference
      screw technique; group 3 (n = 7), anchor technique; and group 4 (n = 7), keyhole
      technique. Each construct was loaded to failure and the groups were compared with
      respect to maximum load in Newtons and deflection at maximum load in millimeters.
      The results were statistically analyzed with 1-way analysis of variance, the
      Bonferroni post hoc test and the Student t test or the nonparametric Mann-Whitney
      U test. RESULTS: The calculated average maximum loads were 229.2 +/- 44.1 N for
      the tunnel technique, 243.3 +/- 72.4 N for the interference screw, 129.0 +/- 16.6
      N for the anchor technique, and 101.7 +/- 27.9 N for the keyhole technique.
      Statistical testing showed no statistically significant differences between
      groups 1 and 2, groups 3 and 4, or groups 2 and 3 with respect to maximum load
      and deflection at maximum load (P = .09/P = .49, P = .41/P = .79, and P = .06/P =
      .82 for load/deflection in the 3 comparisons, respectively). However, all other
      group comparisons revealed significant differences for both parameters (group 1 v
      group 4 [P < .01/P < .01]; group 1 v group 3[P < .01/P = .01]; and group 2 v
      group 4 [P = .007/P = .003]). CONCLUSIONS: The strongest construct was made with
      the interference screw technique, followed by the tunnel, anchor, and keyhole
      techniques. There were no statistically significant differences between the
      interference screw and tunnel techniques with respect to maximum load or
      deflection at maximum load. CLINICAL RELEVANCE: Although it is difficult to
      extrapolate in vitro data to the clinical situation, the interference screw
      technique has better initial biomechanical properties and may produce improved
      clinical outcomes.

PMID- 16084299
TI  - Intra-articular hyaluronan following autogenous osteochondral grafting of the
      knee.
AB  - PURPOSE: The aim of this study was to assess whether intra-articular hyaluronan
      viscosupplementation after osteochondral grafting (mosaic arthroplasty) of the
      knee allowed better graft integration and function in a sheep model. TYPE OF
      STUDY: Experimental study. METHODS: Twelve adult sheep underwent a mosaic
      arthroplasty procedure to a standardized osteochondral defect on the medial
      femoral condyle. One week after surgery the animals were randomized to receive a
      course of weekly intra-articular injections for 5 weeks of either sodium
      hyaluronate solution 25 mg/2.5 mL (HA group) or of a 2.5 mL buffer solution
      (control group). Synovial fluid samples were taken preoperatively, preceding each
      injection, and at 8 and 12 weeks. The animals were euthanized at 12 weeks, the
      knees dissected out, and biomechanical and histologic assessments were made.
      RESULTS: There was no difference in the synovial fluid leukocyte or total protein
      concentration between the groups, but the hyaluronan concentration was
      statistically higher in the HA group. Aggregate moduli of the articular surface
      were statistically higher in the graft articular cartilage in the HA group than
      in the control group, as were the sulphated glycosaminoglycan levels. Histologic
      assessment found more articular cartilage flow in the HA group, whereas there was
      more interstitial tissue present in the interstices between the grafts in the
      control group. CONCLUSIONS: Results from this study suggest that hyaluronan
      viscosupplementation following osteochondral grafting does convey some beneficial
      effects on graft cartilage in the early postoperative period in an ovine model.
      CLINICAL RELEVANCE: This study suggests that, in the early postoperative period,
      hyaluronan supplementation improves articular cartilage survival after
      osteochondral grafting.

PMID- 16084302
TI  - New perceptions of the gut microbiota: implications for future research.

PMID- 16084303
TI  - Physiologic and pathologic interactions of bacteria with gastrointestinal
      epithelium.

PMID- 16084304
TI  - Bacterial regulation of intestinal immune responses.

PMID- 16084305
TI  - Bioecologic control of the gastrointestinal tract: the role of flora and
      supplemented probiotics and synbiotics.

PMID- 16084306
TI  - Probiotics, gut inflammation and barrier function.

PMID- 16084307
TI  - Pediatric applications of probiotics.

PMID- 16084308
TI  - The role of enteric microflora in inflammatory bowel disease: human and animal
      studies with probiotics and prebiotics.

PMID- 16084309
TI  - Lactobacillus GG: bacteriology and clinical applications.

PMID- 16084310
TI  - VSL#3: an analysis of basic and clinical contributions in probiotic therapeutics.

PMID- 16084311
TI  - Saccharomyces boulardii: basic science and clinical applications in
      gastroenterology.

PMID- 16084312
TI  - The use of probiotics in functional bowel disease.

PMID- 16084313
TI  - Use of probiotics in humans: an analysis of the literature.

PMID- 16084315
TI  - Does mixed connective tissue disease exist? Yes.
AB  - For patients who have combined features of rheumatoid arthritis, the limited
      cutaneous form of systemic sclerosis, and inflammatory myopathies, the concept of
      mixed connective tissue disease (MCTD) often helps to predict and diagnose organ
      problems and to educate the patient accordingly. With high titer IgG antibodies
      to U1 ribonucleoprotein (U1-snRNP), this concept is supported by a specific
      serologic marker, and autoantibodies to U1-snRNP and to heterogeneous nuclear
      ribonucleoprotein (hnRNP)-A2 display MCTD specificity with regard to the
      recognized epitopes. In addition, the association of MCTD with HLA-DR4
      distinguishes it from systemic erythematosus lupus and systemic sclerosis, and
      speaks to its being a disease entity, rather than a mixture of yet
      undifferentiated collagen vascular diseases. The authors believe that the concept
      is useful in daily practice and accurate in the idea that MCTD constitutes a
      disease entity of its own.

PMID- 16084316
TI  - Mixed connective tissue disease: still crazy after all these years.
AB  - Mixed connective tissue disease (MCTD) remains a controversial diagnosis. The
      classification criteria have changed significantly from the original description
      by Sharp and colleagues in 1972 after follow-up of the original and other MCTD
      patients. In this article we review the clinical, serologic, and genetic studies
      of MCTD published in the last 10 years and ask if this term is appropriate.

PMID- 16084317
TI  - Autoantibodies in the pathogenesis of mixed connective tissue disease.
AB  - Antibodies to U1-RNP are part of the clinical definition of mixed connective
      tissue disease (MCTD). These antibodies and other well-defined antibodies tend to
      arise together in affected patients. Although still speculative, hypotheses that
      link U1-RNP antibodies to the development of autoimmunity in MCTD and that
      associate U1-RNP antibodies with mechanisms of tissue injury in MCTD have emerged
      and are being tested. Salient features of these hypotheses include: (1) an
      antigen-driven response that is due to impaired clearance of potentially
      immunogenic self-antigens, (2) inadequate B- and T-cell tolerance to RNP
      autoantigens, and (3) immunogenic properties of the RNA component of targeted
      ribonucleoproteins. Further studies are needed to establish whether anti-RNP
      antibodies have prognostic importance that is relevant to practicing clinicians.

PMID- 16084318
TI  - Pulmonary vascular manifestations of mixed connective tissue disease.
AB  - Mixed connective tissue disease (MCTD) refers to a disease process with combined
      clinical features characteristic of systemic lupus erythematous, scleroderma, and
      polymyositis-dermatomyositis. This article focuses on the pulmonary vasculature
      manifestations of MCTD. We briefly discuss associations between MCTD and
      interstitial lung disease, pleural disease, and alveolar hemorrhage.

PMID- 16084319
TI  - Raynaud's phenomenon in mixed connective tissue disease.
AB  - Raynaud's phenomenon affects most patients who have mixed connective tissue
      disease (MCTD) and frequently represents the initial manifestation of the
      disease. It is the cutaneous symptom of a systemic vasculopathy that is
      characterized by intimal fibrosis and blood vessel obliteration that frequently
      leads to visceral involvement, particularly pulmonary hypertension. An
      association between Raynaud's phenomenon and the characteristic autoantibody in
      MCTD, anti-U1-RNP (ribonucleoprotein), is found across the spectrum of rheumatic
      diseases, including undifferentiated connective tissue disease, scleroderma, and
      systemic lupus erythematosus. Capillary nailfold examination represents a
      valuable tool to identify patients who are at risk for MCTD. The goal in the
      therapy of Raynaud's phenomenon in MCTD is to decrease the frequency of attacks,
      to prevent digital ulceration, and to limit progressive vascular damage.
      Therapeutic regimens include the traditional use of calcium channel blockers and
      novel vascular therapies.

PMID- 16084320
TI  - Pediatric-onset mixed connective tissue disease.
AB  - This article discusses the literature on pediatric-onset mixed connective tissue
      disease (MCTD) and adds 34 new cases. Although not benign, pediatric-onset MCTD
      carries less mortality than adult-onset disease.

PMID- 16084321
TI  - Pregnancy in mixed connective tissue disease.
AB  - This article discusses fetal and maternal morbidity in women who have mixed
      connective tissue disease.

PMID- 16084322
TI  - Muscle involvement in mixed connective tissue disease.
AB  - Muscle disease has been recognized as a common feature of mixed connective tissue
      disease (MCTD) since its first description in 1972. In the absence of clinical
      trials that are directed specifically at the myositis of MCTD, patients should be
      treated in the manner that is recommended for other forms of myositis. Myositis
      of MCTD may have a better prognosis than other forms of myositis.

PMID- 16084323
TI  - Other manifestations of mixed connective tissue disease.
AB  - This article describes other manifestations of mixed connective tissue disease
      (MCTD). We focus on inflammatory arthritis, the gastrointestinal tract (the
      esophagus in particular), the kidney, skin, and hematologic changes such as
      thrombocytopenia. Due to the complexity of potential organ involvements in MCTD,
      vigilance with appropriate diagnosis and treatment is warranted.

PMID- 16084324
TI  - The prognosis of mixed connective tissue disease.
AB  - The prognosis for patients who have mixed connective tissue disease (MCTD) varies
      from a benign course to severe progressive disease. In approximately one third of
      patients the clinical symptoms go into long-term remission and the anti-U1 small
      nuclear ribonucleoprotein antibodies disappear. One third of patients have a
      severe, progressive disease course. Persistent morbidity often is attributable to
      arthritis, easy fatiguability, and dyspnea on exertion. The most severe clinical
      manifestation is pulmonary hypertension which contributes to premature death in
      patients who have MCTD. Pulmonary hypertension is associated with proliferative
      vascular abnormalities that involve small pulmonary vessels, rather than
      interstitial lung disease.

PMID- 16084325
TI  - Treatment of mixed connective tissue disease.
AB  - Mixed connective tissue disease (MCTD) is believed to be incurable and seems to
      have a variable prognosis. Some patients have a mild self-limited disease,
      whereas others develop major organ involvement that requires aggressive
      treatment. Because no controlled clinical trials have been performed to guide
      therapy in MCTD, treatment strategies must rely largely upon the conventional
      therapies that are used for similar problems in other rheumatic conditions
      (systemic lupus erythematosus, scleroderma, polymyositis). Given the
      heterogeneous clinical course of MCTD, therapy should be individualized to
      address the specific organ involved and the severity of underlying disease
      activity. Corticosteroids, antimalarials, methotrexate, cytotoxics (most often
      cyclophosphamide), and vasodilators have been used in the treatment of MCTD with
      varying degrees of success.

PMID- 16084327
TI  - Scanning around other options.

PMID- 16084328
TI  - Improved semiautomated quantification of left ventricular volumes and ejection
      fraction using 3-dimensional echocardiography with a full matrix-array
      transducer: comparison with magnetic resonance imaging.
AB  - Our goals were to: (1) develop a technique for 3-dimensional (3D) direct, model
      independent quantitative assessment of left ventricular (LV) volume and ejection
      fraction based on semiautomated detection of LV endocardial surface from
      transthoracic near real-time full matrix-array 3D echocardiographic (FM3DE)
      imaging; (2) evaluate the accuracy of LV volumes obtained with this technique,
      using cardiac magnetic resonance imaging (MRI) measurements as the reference for
      comparison; and (3) determine the effects of contrast enhancement on the accuracy
      of FM3DE measurements. A total of 46 patients underwent 2-dimensional
      echocardiography, FM3DE, and cardiac MRI. End-diastolic volume, end-systolic
      volume, and ejection fraction were derived from endocardial borders manually
      traced from 2-dimensional echocardiographic images and from semiautomatically
      detected LV cavity from FM3DE data. In 14 patients, FM3DE was also acquired with
      contrast. All measurements were compared with MRI values using linear regression
      and Bland-Altman analyses. FM3DE was feasible in 44 of 46 patients with LV
      volumes < 345 mL. LV volumes and ejection fraction computed from FM3DE resulted
      in higher levels of agreement with MRI than conventional 2-dimensional
      echocardiography, with lower interobserver variability. With contrast
      enhancement, FM3DE significantly underestimated LV volumes and showed increased
      interobserver variability. Semiautomated LV endocardial surface detection from
      FM3DE images is feasible and results in fast and accurate assessment of LV
      function.

PMID- 16084329
TI  - Regional aortic function is correlated with intima-media thickness-insights from
      three-dimensional echocardiography.
AB  - BACKGROUND: Thickening of arterial intima and the presence of atherosclerotic
      plaques may influence vessel pulsation by increasing the wall stiffness. There
      are no data available concerning regional changes in aortic elasticity in
      relation with local wall thickness and the magnitude of atherosclerosis. METHODS:
      The study group comprised 48 patients (33 men, age 54 +/- 11 years) referred for
      transesophageal echocardiography. Reconstruction of 2-cm segments of aorta was
      divided by coaxial planes into 4 longitudinal sections. Thereafter, diastolic and
      systolic radius, thickness of atherosclerotic plaques, and intima-media thickness
      (IMT) in each section were measured. The relative change in regional aortic lumen
      (pulsation) was measured and regional beta-index was calculated. In total, 192
      aortic sections were analyzed. RESULTS: The volume of the examined sections of
      the aortic segments ranged from 0.6 to 4.1 cm3 (mean 1.6 +/- 0.7 cm3) in systole
      and from 0.5 to 3.7 cm3 (mean 1.4 +/- 0.7 cm3) in diastole. The pulsation of the
      aortic sections varied from 0.04 to 0.78 cm3 (mean 0.21 +/- 0.13 cm3), which
      constituted 1% to 21% (mean 6 +/- 4%) of the section volume. The thickness of
      atherosclerotic plaques in the studied aortic sections ranged from 0.03 to 1.87
      mm (mean 0.31 +/- 0.26 mm) and IMT was within the range 1.28 to 3.61 mm (mean
      1.87 +/- 0.39 mm). The regional beta-index of the individual section ranged from
      1.6 to 97.1 (mean 12.5 +/- 14.6). The regional beta-index was statistically
      significantly dependent on the IMT (r = 0.43, P < .001), but not on the thickness
      of atherosclerotic plaques (P = .96). The variability of regional beta-index,
      defined as the difference between the highest and the lowest beta-index in the
      sections of the same aortic segment, ranged from 1.7 to 83.1 (mean 20.0 +/- 20.7)
      and was borderline correlated with the IMT (r = 0.26, P = .07), but not with the
      thickness of atherosclerotic plaques (P = .87). CONCLUSIONS: Three-dimensional
      echocardiography facilitates quantitative analysis of aortic wall stiffness and
      regional beta-index measurements. The local aortic wall beta-index and its
      regional variability is dependent on IMT, but not on the thickness of
      atherosclerotic plaques.

PMID- 16084330
TI  - Quantitative analysis of left atrial function during left ventricular ischemia
      with and without left atrial ischemia: a real-time 3-dimensional
      echocardiographic study.
AB  - Left atrial (LA) systolic and diastolic function were analyzed in an animal model
      of acute left ventricular ischemia with LA ischemia by proximal left circumflex
      coronary artery occlusion or without LA ischemia by midleft anterior descending
      coronary artery occlusion (7 sheep in each group). LA pressures and LA volumes
      were simultaneously recorded using a catheter and real-time 3-dimensional
      echocardiography, respectively. LA stroke volume represented 63% of left
      ventricular stroke volume during left anterior descending coronary artery
      occlusion, but only 32% during left circumflex coronary artery occlusion. This
      animal study with 3-dimensional echocardiographic determination of absolute LA
      volumes demonstrated dramatic depression of LA function during proximal left
      circumflex coronary artery occlusion as compared with left anterior descending
      coronary artery occlusion.

PMID- 16084331
TI  - Morphological determinants of subaortic stenosis in hypertrophic cardiomyopathy:
      insights from real-time 3-dimensional echocardiography.
AB  - Real-time 3-dimensional echocardiography allows a comprehensive evaluation of
      left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic
      cardiomyopathy. The anterior segment of the anterior mitral leaflet is essential
      in the development of the LVOT pressure gradient.

PMID- 16084332
TI  - Insight into normal mitral and tricuspid annular dynamics in pediatrics: a real
      time three-dimensional echocardiographic study.
AB  - BACKGROUND: Although there are animal or adult studies analyzing annular motion
      of the mitral valve (MV) or tricuspid valve (TV) separately, there are no data
      analyzing interaction between the MV and TV, or data from the pediatric
      population. METHODS: A total of 17 healthy children (age 3-15 years) were
      enrolled in this study. Using real-time 3-dimensional echocardiography, annular
      area, perimeter, segmental diameter, and bending angle were obtained and
      analyzed. RESULTS: MV area increased during systole, in contrast to TV area,
      which decreased. TV area demonstrated a greater reduction of lateral diameter
      during systole. Bending motion became most acute in early diastole, which was
      greater for the TV. CONCLUSIONS: MV area change differs from adults, which may be
      explained by a more compliant myocardium in children. Greater lateral forces on
      TV prevent it from becoming circular, thus, preserving valve competency. Both
      valves show a bending motion, which becomes most prominent during isovolumic
      relaxation continuing into early diastole for the TV, suggesting a relationship
      with torsional forces within the ventricles.

PMID- 16084333
TI  - Assessment of papillary muscle function in patients with inferior wall myocardial
      infarction using Doppler tissue imaging.
AB  - OBJECTIVES: We sought to assess the relationship between infarct status and
      systolic contractile function of papillary muscle (PM) for patients with inferior
      wall myocardial infarction (MI). METHODS: Peak systolic velocity (V) of
      posteromedial PM, systolic strain (epsilon) of posteromedial PM (epsilonPM), V of
      adjacent inferior wall, and of adjacent inferior wall (epsilonW) were calculated
      from color Doppler tissue imaging images obtained at apical views in 25 patients
      with inferior MI and in 13 healthy control subjects. All 25 patients with MI
      underwent magnetic resonance imaging to assess the infarct status of PM. RESULTS:
      Compared with the control subjects, patients with MI had significantly lower V of
      adjacent inferior wall (5.0 +/- 0.8 vs 4.4 +/- 1.1 cm/s, P = .049) and V of
      posteromedial PM (4.9 +/- 0.8 vs 4.0 +/- 1.2 cm/s, P = .005), and less systolic
      deformation, as demonstrated by epsilonW (-17 +/- 3 vs -6 +/- 5%, P < .001) and
      epsilonPM (-24 +/- 5 vs -11 +/- 6%, P < .001). There was a weak positive
      correlation between epsilonW and epsilonPM (r = 0.393, P = .052) for patients
      with MI. Magnetic resonance imaging showed total infarct of PM in 14 patients
      (group A), with the remaining 11 revealing either normal perfusion or partial
      infarct of PM (group B). Although epsilonW was similar in groups A and B (-5 +/-
      5% vs -8 +/- 6%, P = .20), epsilonPM was significantly lower in group B (-7 +/-
      4% vs -16 +/- 4%, P = .004). CONCLUSIONS: In patients with inferior wall MI,
      infarct status of the PM is variable and determines its systolic contractile
      function, which can be quantified by epsilon measurement using Doppler tissue
      imaging.

PMID- 16084334
TI  - Detection of prominent left anterior descending coronary artery stenosis for
      patients with stable angina using Doppler tissue echocardiography.
AB  - The midseptum has an elective left anterior descending coronary artery (LAD)
      supply. Septal peak velocity (PkV) and myocardial velocity gradient (MVG) were
      studied at rest with M-mode Doppler tissue echocardiography during the cardiac
      cycle including the septal active relaxation (SAR) outward wall motion preceding
      isovolumic relaxation. In all, 33 patients had significant multivessel coronary
      artery disease. Group A (15 patients) had prominent LAD stenosis. Group B (18
      patients) had prominent circumflex (15) or right (3) coronary artery stenoses.
      The goal was to detect a prominent LAD stenosis. During SAR, sensitivity to
      detect a prominent LAD stenosis was 86% for PkV < 20 mm/s and 80% for MVG < 1.1
      s(-1); specificity was 83% for both variables. During systole, sensitivity was
      86% with a 55% specificity for MVG < 2.0 s(-1), whereas sensitivity was 73% and
      specificity 66% for PkV < 30 mm/s. Areas under receiver operating characteristic
      curves were over 0.90 during SAR and only 0.70 for PkV and 0.80 for MVG during
      systole. In multivessel coronary artery disease, SAR variables better identified
      a prominent LAD stenosis than systolic variables. Moreover, SAR PkVs were
      informative per se, whereas systole required MVG calculation.

PMID- 16084335
TI  - Impact of chronic left ventricular preload and afterload on Doppler tissue
      imaging velocities: a study in congenital heart disease.
AB  - BACKGROUND: Doppler tissue imaging (DTI) velocities have been reported to be
      relatively independent of changes in ventricular loading conditions in adult
      studies. The clinical impact of altered left ventricular (LV) preload and
      afterload on DTI velocities in children with congenital heart disease has not
      been adequately evaluated. The purpose of this study was to evaluate the impact
      of chronic LV preload and afterload on DTI velocities in children with isolated
      ventricular septal defect and aortic valve stenosis compared with age-matched
      normal and abnormal (dilated cardiomyopathy) control groups. METHODS: From an
      apical 4-chamber view, DTI velocities were obtained at the cardiac base at the
      lateral mitral annulus, lateral tricuspid annulus, and interventricular septum in
      early diastole, late diastole, and ventricular systole. RESULTS: The majority of
      DTI velocities did not change significantly in patients with increased LV
      preload. Patients with increased LV afterload had significantly decreased
      systolic and early diastolic DTI velocities at both the lateral mitral annulus
      and ventricular septum compared with control subjects. Children with dilated
      cardiomyopathy had significantly decreased DTI velocities at all myocardial
      annular locations. CONCLUSIONS: We conclude that increases in chronic LV preload
      do not significantly affect the majority of DTI velocities in children with
      ventricular septal defects. In addition, significantly increased chronic LV
      afterload in children with aortic valve stenosis is associated with decreased DTI
      velocities in the absence of other identifiable abnormalities of LV function.
      Decreased DTI velocity may be secondary to increased afterload or may
      alternatively be an early marker of subclinical LV longitudinal dysfunction.

PMID- 16084336
TI  - Increased right ventricular afterload induces postsystolic thickening of the
      ventricular septum in nonischemic hearts.
AB  - BACKGROUND: We aimed to assess whether myocardial postsystolic thickening (PST)
      can be induced by an acute increase in right ventricular (RV) afterload and,
      thus, demonstrate that PST may have a nonischemic cause. METHODS: In 8
      anesthetized open-chest pigs, radial strains of the interventricular septum (IVS)
      and left ventricular inferolateral wall were obtained by Doppler tissue
      echocardiography before and during constriction of the pulmonary artery. RESULTS:
      After each constriction, RV peak systolic pressure increased from 30 +/- 5 to 57
      +/- 8 mm Hg (P < .001). Peak systolic radial strain of the IVS decreased from
      20.8% +/- 5.3% to 9.5% +/- 4.1% (P = .003), and PST of the IVS increased from
      0.3% +/- 0.5% to 6.1% +/- 4.8% (P = .01). The onset of PST started 41 +/- 20
      milliseconds after peak negative dP/dt of RV pressure. The inferolateral wall did
      not show PST. CONCLUSION: An acute increase in RV pressure causes a significant
      reduction in peak systolic strain of the IVS associated with the nonischemic
      appearance of PST.

PMID- 16084337
TI  - High prevalence of important cardiac findings in patients with peripheral
      arterial disease referred for echocardiography.
AB  - BACKGROUND: Patients with peripheral arterial disease (PAD) diagnosed by ankle
      brachial index evaluation are known to have high cardiovascular mortality.
      Although this has primarily been attributed to coexistent coronary artery
      disease, the prevalence of abnormal echocardiographic findings for patients with
      PAD has not been studied. Our goal was to study the association between PAD and
      clinically important echocardiographic findings in symptomatic patients with PAD
      referred for echocardiography. METHODS: Eligible patients were identified from a
      database of 615 consecutive patients referred for clinically indicated ankle
      brachial index evaluation in our vascular laboratory. Patients were included (n =
      309) if they also had a complete transthoracic echocardiogram in the digital
      echocardiogram database at our institution. Final transthoracic echocardiographic
      reports were retrospectively reviewed for study indication and clinically
      important echocardiographic findings. Patients with PAD (ankle-brachial index <
      0.9) (n = 190) were compared with patients without PAD (n = 119). RESULTS:
      Patients with PAD were found to have a high prevalence of clinically important
      echocardiographic findings, and significantly more clinically important
      echocardiographic findings (61.6% vs 35.3%, P < .001), including more left
      ventricular (LV) dysfunction and aortic stenosis, than patients without PAD. On
      multivariate logistic regression analysis, the presence of PAD was found to be an
      independent predictor of LV ejection fraction < 50% (odds ratio 2.86, 95%
      confidence interval 1.54-5.32, P = .001), LV ejection fraction < 35% (odds ratio
      2.48, 95% confidence interval 1.22-5.07, P = .02), and any clinically important
      echocardiographic finding (odds ratio 2.65, 95% confidence interval 1.61-4.36, P
      < .001). CONCLUSION: In symptomatic patients with PAD referred for
      echocardiography, there is a high prevalence of clinically important
      echocardiographic findings, including LV dysfunction, and PAD appears to be an
      independent predictor of an abnormal echocardiogram. These findings suggest that
      a prospective echocardiographic screening study in symptomatic patients with PAD
      is warranted.

PMID- 16084338
TI  - Prevalence of echocardiographically detected ventricular asynchrony in patients
      with left ventricular systolic dysfunction.
AB  - OBJECTIVES: QRS complex width is not an accurate marker of cardiac asynchrony.
      Our aims were to determine the prevalence of cardiac asynchrony by Doppler
      echocardiography for patients with left ventricular (LV) dysfunction and to
      evaluate whether QRS width is a reliable method for detecting asynchrony.
      METHODS: In all, 316 consecutive patients with a LV ejection fraction less than
      40% from 13 hospitals comprised the study group. Interventricular asynchrony was
      defined by the interventricular mechanical delay. Intraventricular asynchrony was
      evaluated using the calculation of the septal-to-posterior wall motion delay, the
      difference between time from Q wave to LV ejection end, and time from Q wave to
      the end of the systolic wave of the most delayed basal segment by Doppler tissue
      imaging, the SD of the time from the Q wave to the end of the systolic wave of 4
      basal segments, and the maximum difference in the time from the Q wave to the end
      of the systolic wave of all 4 basal segments. RESULTS: Mean age was 62.14 +/-
      13.5 years (234 men; 74.1%). Interventricular asynchrony was present in 50
      (26.2%) patients in the narrow QRS group and in 57 (55.3%) patients in the
      prolonged QRS group (P < .001). Intraventricular asynchrony was present in 40
      (20.8%) to 136 (72.8%) patients in the narrow QRS group and in 27 (26.2%) to 82
      (79.6%) in the prolonged QRS group, depending on the method used. CONCLUSIONS:
      Cardiac asynchrony is highly prevalent for patients with LV dysfunction but there
      is a very poor agreement among the different methods used to detect it.
      Interventricular asynchrony is more prevalent for patients with prolonged QRS but
      intraventricular asynchrony is irrespective of the QRS duration. Further studies
      are needed to evaluate which method is the best to detect cardiac
      resynchronization therapy responders.

PMID- 16084339
TI  - Biphasic Doppler pattern of the descending thoracic aorta: a new
      echocardiographic finding in patients with aortic valve stenosis.
AB  - A total of 59 patients (> or = 65 years of age) with normal left ventricular
      function (ejection fraction > 50%) and varying degrees of aortic valve structure
      and hemodynamics (normal to severely stenotic) were screened; 50 were
      subsequently enrolled. Continuous wave Doppler echocardiography in the descending
      thoracic aorta showed two general patterns: (1) in aortic stenosis, the pattern
      consisted of two peak systolic velocity components (S1 and S2); and (2) in normal
      aortic valve function, the pattern was a uniphasic signal with a single peak
      systolic velocity component. The new Doppler pattern yielded 95% sensitivity and
      90% specificity in the detection of clinically significant aortic valve stenosis,
      and 92% sensitivity and 70% specificity in the detection of severe aortic valve
      stenosis. Sensitivity was 96% in uniphasic signals during normal aortic valve
      function by conventional 2-dimensional and Doppler criteria. This article
      introduces characteristics of this Doppler velocity profile as a new diagnostic
      finding of aortic valve stenosis.

PMID- 16084340
TI  - Validation of noncompaction criteria in dilated cardiomyopathy, and valvular and
      hypertensive heart disease.
AB  - BACKGROUND: Echocardiographic characteristics typical of isolated left
      ventricular noncompaction (IVNC) have been well defined. The aim of this study
      was to validate diagnostic criteria of IVNC in valvular or hypertensive heart
      disease (HHD) or dilated cardiomyopathy. METHODS: We conducted a retrospective
      analysis of records and blind review of videotapes of all 19 patients with IVNC
      seen within 7 years in comparison with randomly selected patients from the same
      study period with dilated cardiomyopathy (31 patients), HHD (22 patients), and
      chronic severe valvular heart disease: mitral regurgitation (22 patients); aortic
      regurgitation (20); and aortic stenosis with bicuspid (22) or tricuspid (22)
      valves. RESULTS: Clinical characteristics and electrocardiographic findings did
      not differ between IVNC and other diseases. In IVNC, all patients had
      noncompacted (NC) segments with a 2-layered structure and wall thickening, and in
      most patients perfused recesses (95%) or hypokinetic segments (89%) were present.
      Both hypertrabeculation or presence of a meshwork were specific for IVNC, but the
      sensitivity for IVNC was only 11% for hypertrabeculation, respectively, 68% for
      meshwork. In dilated cardiomyopathy, perfused recesses (48%) and a 2-layered
      structure (26%) were seen but without wall thickening of these segments; all NC
      criteria including wall thickening were fulfilled in one patient (3%) only. In
      valvular heart disease or HHD, perfused recesses and a 2-layered myocardium were
      rare: two patients (5%) with aortic stenosis and one patient with HHD (5%) had
      NC. Although in IVNC wall thickening was confined to the 2-layered myocardial
      segments, it was diffuse in other diseases. CONCLUSIONS: Although some NC
      criteria are occasionally found in other heart disease, the combination of all
      criteria is very specific. All criteria of NC are rarely met in other disease
      than IVNC (< or = 5%).

PMID- 16084341
TI  - Impact of chronic obstructive pulmonary disease with pulmonary hypertension on
      both left ventricular systolic and diastolic performance.
AB  - BACKGROUND: The effects of chronic obstructive pulmonary disease (COPD) on right
      ventricular (RV) systolic and diastolic functions and left ventricular (LV)
      diastolic function have been shown. Whereas LV myocardial performance index
      (LVMPI), which incorporates ejection and isovolumic relaxation and contraction
      times and is an index of global ventricular function, has not yet been evaluated
      in COPD. METHODS: Our study population consisted of 24 age-matched control
      subjects (group 1), 24 patients with COPD without pulmonary hypertension (group
      2), and 20 patients with COPD with pulmonary hypertension (group 3). Pulmonary
      function tests, analyses of arterial blood gases, and transthoracic
      echocardiographic examination were performed. RV myocardial performance index
      (RVMPI) and LVMPI were obtained by pulsed wave Doppler tissue. RESULTS: RVMPI was
      higher in both group 2 (0.61 +/- 0.15) and group 3 (0.94 +/- 0.27) than group 1
      (0.41 +/- 0.08) (P = .038 and P< .001, respectively), and was higher for group 3
      than in group 2 (P = .018). LVMPI was higher for group 3 (0.77 +/- 0.25) than in
      both group 1 (0.49 +/- 0.08) and group 2 (0.59 +/- 0.10) (P = .001 and P = .037,
      respectively). However, difference between groups 1 and 2 was not significant (P
      > .05). For patients with COPD, LVMPI was positively correlated with age, heart
      rate, pulmonary arterial systolic pressure, RVMPI, and partial pressure of carbon
      dioxide, and negatively correlated with tricuspid annular plane systolic
      excursion, forced expiratory volume in 1 second, and partial pressure of oxygen.
      In multiple linear regression analysis (R2 = 0.676), LVMPI was independently
      associated with forced expiratory volume in 1 second (Beta = 0.549, P = .017),
      pulmonary arterial systolic pressure (Beta = 0.488, P = .014), and RVMPI (Beta =
      0.278, P = .042). CONCLUSIONS: Both LV systolic and diastolic functions are
      impaired in COPD, especially in patients with pulmonary hypertension. This
      impairment is independently associated with pulmonary arterial systolic pressure,
      RVMPI, and forced expiratory volume in 1 second.

PMID- 16084342
TI  - Intermittent coronary sinus occlusion complicating coronary sinus cannulation
      during coronary artery bypass operation.
AB  - Coronary sinus (CS) thrombosis is a rare event, usually complicating invasive
      procedures that cause trauma to the CS. Based on anecdotal case reports, this
      pathology is frequently associated with serious complications and is commonly
      fatal. We describe a case of intermittent CS thrombosis resulting from CS
      cannulation during coronary artery bypass grafting operation. This complication
      was further complicated by myocardial infarction, left ventricular free wall
      rupture, and pseudoaneurysm formation. The characteristic echocardiographic
      findings and a review of the literature on this rare complication are presented.

PMID- 16084343
TI  - Myocardial contrast echocardiography with 1.5-harmonic imaging in the diagnosis
      of cardiac malignant lymphoma.
AB  - We applied myocardial contrast echocardiography with 1.5-harmonic imaging to an
      atrioventricular groove tumor in a patient with malignant lymphoma. Contrast
      echocardiography initially showed one centric legion and some patchy echogenic
      foci within the tumor, all of which were indicative of arterial components.
      Subsequently, the tumor was enhanced homogenously, reflecting parenchymal
      hyperperfusion. These findings were consistent with previous observations of
      malignant lymphoma using color Doppler. We believe that myocardial contrast
      echocardiography could afford an important clue to the histologic diagnosis of
      cardiac tumors.

PMID- 16084344
TI  - Aortic hypoplasia and right ventricular outflow tract obstruction in a young man
      with uncontrolled hypertension.
AB  - We report the case of a 35-year-old man who presented to hospital with
      symptomatic uncontrolled hypertension. He had no other conventional
      cardiovascular risk factors, but did have previous cataract surgery and patent
      ductus arteriosus repair. Echocardiography revealed normal valves, right
      ventricular outflow tract obstruction, and heavy calcification of the aortic root
      compromising luminal diameter. Pulmonary angiography confirmed supravalvular and
      subvalvular pulmonary stenosis. Aortography showed hypoplasia of the entire
      aortic trunk extending into the iliac arteries, but without involvement of other
      major branches. A possible unifying diagnosis, with the combination of aortic
      hypoplasia, pulmonary artery stenosis, patent ductus arteriosus, and cataracts,
      was believed to have been congenital rubella syndrome. Although associated with
      numerous cardiovascular abnormalities, aortic hypoplasia is an extremely rare
      manifestation of congenital rubella that, to our knowledge, has been reported in
      only two cases in the literature to date.

PMID- 16084345
TI  - Tako tsubo cardiomyopathy (transient left ventricular apical ballooning): case
      report of a myocardial perfusion echocardiogram study.
AB  - We are reporting a case of Tako tsubo cardiomyopathy (transient left ventricular
      apical ballooning) in the Western population identified by a perfusion
      echocardiogram that demonstrated perfusion defect at baseline in the apical and
      adjacent walls that was incongruous to the wall-motion abnormality. The perfusion
      defect improved within 72 hours on a repeated study indicating that
      microvasculature disruption is a key feature of this enigmatic cardiomyopathy.

PMID- 16084346
TI  - Multiple right coronary artery fistulae in a patient with diffuse hypertrophic
      cardiomyopathy: a case report.

PMID- 16084347
TI  - Partial or total anomalous pulmonary venous drainage caused by malposition of
      septum primum: echocardiographic description of a rare variant of anomalous
      pulmonary venous drainage.
AB  - We describe the echocardiographic findings in 9 patients, a rare variant of
      partial and total anomalous pulmonary venous drainage directly to the morphologic
      right atrium, caused by malposition of septum primum. Displacement of septum
      primum to the morphologic left atrium was present in all 9 cases leading to
      partial or complete anomalous drainage of pulmonary veins to the morphologic
      right atrium. However, all pulmonary veins were connecting normally to the
      morphologic left atrium. The views that best demonstrated the deviation of septum
      primum were subxiphoid coronal, apical 4-chamber, and parasternal long-axis.

PMID- 16084349
TI  - New antithrombotics in the treatment of thromboembolic disease.
AB  - New insights into the in vivo function of the coagulation system have resulted in
      the development of new antithrombotic agents with a more specific point of impact
      and more reliable pharmacological properties. Inhibition of coagulation can be
      achieved by specific thrombin inhibitors (e.g. melagatran), agents specifically
      targeted at factor Xa (e.g. pentasaccharides), and by tissue factor/factor VIIa
      blockers (e.g. recombinant NAPc2). In some situations, these agents are more
      effective and safer than the antithrombotics currently used. However, the major
      difference may be that the newer generation of antithrombotics does not require
      repeated laboratory control and dose adjustment to obtain a stable level of
      anticoagulation; therefore, they are more suitable for application in clinical
      practice. In this overview, we will briefly discuss the various new compounds
      that have recently become available or that will be introduced into clinical
      medicine in the near future and their relative efficacy and safety in comparison
      to currently used antithrombotic agents.

PMID- 16084350
TI  - Deep vein thrombosis: Current diagnostic strategy.
AB  - Over the last 15 years, diagnostic strategies to diagnose deep vein thrombosis
      (DVT) and pulmonary embolism (PE) have changed significantly. The gold standard
      for detecting DVT is still venography, but invasivity, radiation, contrast media,
      and the painful injection in pedal veins are limiting factors for initial and
      repeat examinations. The introduction of DVT scores, D-dimer testing, and venous
      ultrasound has made venography replaceable in most cases. This review focuses on
      different diagnostic strategies for clinicians in hospitals as well as for
      general practitioners using practical approaches.

PMID- 16084351
TI  - Diagnostic methods in pulmonary embolism.
AB  - Diagnosing pulmonary embolism (PE) is challenging since clinical signs and
      symptoms are non-specific. The diagnostic tests available for demonstrating PE
      all have their drawbacks and are often costly and consume considerable amounts of
      resources. Simple tools that have become available in the last several years
      include clinical prediction rules and D-dimer testing. Assessment of the clinical
      probability, combined with a D-dimer test, can limit the need for additional
      diagnostic tests by 30%. For outpatients with a normal, sensitive ELISA D-dimer
      test and a low-to-moderate clinical probability, PE can safely be ruled out.
      Pulmonary angiography, though still the gold standard, is rarely used nowadays
      because of its invasiveness, its high costs and limited availability, and the
      declining experience of radiologists with the technique. Two imaging techniques-
      lung scintigraphy and helical CT--are the diagnostic methods of choice. A normal
      perfusion lung scan can safely exclude PE. However, 55-65% of patients have
      indeterminate lung scan results, making additional imaging tests necessary.
      Helical CT is increasingly being used as the first-line test because it can
      directly visualize a thromboembolus, it can suggest an alternative diagnosis, and
      there is excellent inter-observer agreement. A normal helical CT, followed by
      compression ultrasonography of the leg veins, can safely rule out PE. Finally,
      the safety of withholding anticoagulant treatment from patients with a normal
      multi-row detector helical CT as the sole test has not yet been demonstrated.

PMID- 16084352
TI  - New antithrombotics in the prevention of thromboembolic disease.
AB  - New anticoagulants are under development to improve on current ones that,
      although effective, have limitations in efficacy, safety and convenience. We have
      reviewed the use of these agents as thromboprophylactic drugs. These new agents
      have more specific modes of action and can be divided into three groups.
      Inhibitors of the initiation of coagulation work via inhibition of the factor
      VIIa/tissue factor complex. Inhibitors of propagation of coagulation include
      parenteral and oral factor Xa inhibitors, factor IXa inhibitors, inhibitors of
      factor Va and VIIIa, activated Protein C, soluble thrombomodulin and SNAC
      Heparin. Finally, direct inhibitors of thrombin are under development both for
      parenteral and oral administration. Several new drugs, such as fondaparinux,
      hirudin, argatroban, bivalirudin and ximelagatran, have already been licensed for
      specific indications and are being investigated for more general usage. Other
      drugs reviewed are in much earlier stages of development.

PMID- 16084353
TI  - Ximelagatran: a clinical perspective.
AB  - Ximelagatran is a novel oral anticoagulant belonging to a class of drugs known as
      direct thrombin inhibitors. Numerous recent large-scale, randomised controlled
      clinical trials have given the drug a large clinical platform. These include data
      on the thromboprophylaxis of venous thromboembolism following major orthopaedic
      surgery and knee arthroscopy, as well as in the treatment of deep vein thrombosis
      and prevention of stroke with nonvalvular atrial fibrillation. One phase II study
      has also shown the efficacy and safety of ximelagatran in secondary prevention
      post-myocardial infarction. Unfortunately, approximately 6% of patients develop
      usually self-limiting derangement of liver dysfunction, and frequent monitoring
      of liver function is likely to be recommended for the first 6 months of
      treatment. Unlike the vitamin K antagonists, ximelagatran has a wide therapeutic
      interval with few food, alcohol or drug interactions, and it does not require
      anticoagulant monitoring. The aim of this overview is to review the clinical
      trials pertaining to this new drug, which is the first new oral anticoagulant for
      over 60 years, and one that is likely to influence our management of thrombosis
      related disorders.

PMID- 16084354
TI  - A study of hospital discharges for venous thromboembolism in the south of Spain.
      An analysis of 19,170 cases from a regional database from 1998 to 2001.
AB  - BACKGROUND: Our objective was to learn about the incidence of hospitalization for
      venous thromboembolism (VTE) in the public health care system in Andalusia and to
      define the profile of the patients, with special reference to the Department of
      Internal Medicine. METHODS: We analyzed the discharged data set of 32 hospitals
      in the Andalusian Health Care Service between 1998 and 2001, identifying the
      cases in whom the diagnosis was VTE. The age, sex, length of stay, outcome,
      number of diagnoses, diagnosis-related group (DRG), and coded procedures were
      studied. RESULTS: During the period studied, there were 2,228,894 discharges,
      19,170 of which involved VTE. In 8494 of these, VTE was the cause of the
      admission. Some 3961 patients (46.6%) were admitted for pulmonary embolism (PE);
      45% were discharged from internal medicine, 41% from pneumology, and 14% from
      other departments. The average patient age was 65, the length of stay 13.8 days,
      and the global in-hospital mortality rate 13%. Some 4533 cases (53.4%) were
      admitted due to deep vein thrombosis (DVT): 38.5% to internal medicine, 21.30% to
      general surgery, 12.35% to angiology, and the remainder to other departments. The
      length of stay was 10.6 days with an in-hospital mortality rate of 2.20%. In 7721
      cases, VTE was the secondary diagnosis (after excluding 2955 cases of superficial
      thrombophlebitis of the upper limbs); 74% was associated with a medical DRG.
      CONCLUSIONS: VTE is a frequent pathology in our hospitals. It shows a great
      variability in clinical practice although there are differences between patients
      treated by different specialists. VTE as secondary diagnosis was more frequent in
      medical inpatients.

PMID- 16084355
TI  - Did the ancient Greeks have a god of internal medicine?

PMID- 16084356
TI  - Isolated lytic bone lesion as extramedullary disease in chronic myelogenous
      leukemia: a report of three new cases.
AB  - This short report describes three patients with chronic myeloid leukemia and
      isolated extramedullary bone disease with isolated lytic bone lesions. All these
      patients were in chronic phase when skeletal blast crisis took place. All the
      patients developed a full-blown blastic crisis within 3 months, with a rapidly
      fatal outcome, despite several intensive therapies.

PMID- 16084357
TI  - Reversible posterior leukoencephalopathy associated with postpartum HELLP
      syndrome.
AB  - We describe a case of a severe, immediate postpartum HELLP syndrome (hemolysis,
      elevated liver enzyme levels, low platelet count) with reversible posterior
      leukoencephalopathy (RPLS) characterized by generalized seizure, altered mental
      status, and visual loss in a 37-year-old primigravid woman. Magnetic resonance
      brain imaging showed diffuse subcortical edema, which resolved completely after 2
      weeks along with complete symptom regression. The pathogenesis of RPLS is
      discussed and the importance of a prompt diagnosis is emphasized, as is the
      crucial role of rapid blood pressure reduction.

PMID- 16084358
TI  - Purple digit syndrome and warfarin-induced skin necrosis.
AB  - Warfarin is used extensively in clinical practice for numerous indications. It is
      generally safe. Bleeding is the major risk of warfarin; several uncommon adverse
      skin manifestations may also be associated with its use. These range from
      ecchymoses and purpura, haemorrhagic necrosis and maculopapular vesicular
      urticarial eruptions to cutaneous necrosis, purple digit syndrome and warfarin
      induced skin necrosis. Early recognition and diagnosis of these adverse reactions
      are important to avoid morbidity and possible mortality. All health professionals
      should be aware of these complications.

PMID- 16084359
TI  - Is polydipsia sometimes the cause of oxcarbazepine-induced hyponatremia?
AB  - Hyponatremia is a commonly encountered clinical problem with potentially severe
      complications. Among the underlying implicated etiologies are medications such as
      oxcarbazepine, which has been well documented and attributed to the syndrome of
      inappropriate antidiuretic hormones (SIADH). We report the case of a 28-year-old
      woman with a diagnosis of secondary antiphospholipid syndrome who presented with
      asymptomatic hyponatremia secondary to excessive water intake after oxcarbazepine
      ingestion, suggesting a new mechanism for oxcarbazepine-induced hyponatremia.

PMID- 16084360
TI  - Chronic disseminated intravascular coagulation caused by an aorto-bifemoral
      aneurysm.
AB  - This article reports the case of a patient with chronic disseminated
      intravascular coagulation that led to the diagnosis of an otherwise asymptomatic
      aorto-bifemoral aneurysm. The bleeding disorder completely resolved with the
      surgical resection of the aneurysm. Fibrinogen replacement therapy prior to
      invasive diagnostic procedures resulted in good hemosthasia.

PMID- 16084361
TI  - Bone marrow fibrosis and caseating granulomas associated with intravesicular BCG
      treatment.
AB  - Intravesicular instillation of bacille Calmette-Guerin (BCG), an attenuated
      variant of the virulent strain of Mycobacterium bovis, has been extensively used
      as the treatment of choice for bladder cancer since first approved in 1976.
      Adverse effects of treatment are rare and mostly local, with systemic reactions
      complicating up to 5% of patients. The majority of serious side effects have
      occurred in immunocompromised patients. Even more rare is bone marrow
      involvement. Only two previous cases are reported in the medical English
      literature; in these cases, the granulomas were non-caseating. We describe a
      patient who developed fever and pancytopenia associated with mycobacterial
      infection after intravesicular instillation of BCG. Caseating granulomas were
      seen in the bone marrow biopsy and, later, bone marrow fibrosis developed
      gradually, in spite of successful treatment with antimycobacterial agents.

PMID- 16084363
TI  - Severe myopathy induced by the co-administration of simvastatin and itraconazole.

PMID- 16084362
TI  - Systemic venous thromboembolism with membranous nephropathy and
      hyperhomocysteinemia.

PMID- 16084364
TI  - Biosynthesis of medium chain length poly(3-hydroxyalkanoates) (mcl-PHAs) by
      Comamonas testosteroni during cultivation on vegetable oils.
AB  - Comamonas testosteroni has been studied for its ability to synthesize and
      accumulate medium chain length poly(3-hydroxyalkanoates) (mcl-PHAs) during
      cultivation on vegetable oils available in the local market. Castor seed oil,
      coconut oil, mustard oil, cotton seed oil, groundnut oil, olive oil and sesame
      oil were supplemented in the mineral medium as a sole source of carbon for growth
      and PHAs accumulation. The composition of PHAs was analysed by a coupled gas
      chromatography/mass spectroscopy (GC/MS). PHAs contained C6 to C14 3-hydroxy
      acids, with a strong presence of 3-hydroxyoctanoate when coconut oil, mustard
      oil, cotton seed oil and groundnut oil were supplied. 3-hydroxydecanoate was
      incorporated at higher concentrations when castor seed oil, olive oil and sesame
      oil were the substrates. Purified PHAs samples were characterized by Fourier
      Transform Infrared (FTIR) and 13C NMR analysis. During cultivation on various
      vegetable oils, C. testosteroni accumulated PHAs up to 78.5-87.5% of the cellular
      dry material (CDM). The efficiency of the culture to convert oil to PHAs ranged
      from 53.1% to 58.3% for different vegetable oils. Further more, the composition
      of the PHAs formed was not found to be substrate dependent as PHAs obtained from
      C. testosteroni during growth on variety of vegetable oils showed similar
      compositions; 3-hydroxyoctanoic acid and/or 3-hydroxydecanoic acid being always
      predominant. The polymerizing system of C. testosteroni showed higher preference
      for C8 and C10 monomers as longer and smaller monomers were incorporated less
      efficiently.

PMID- 16084365
TI  - Application of rotary microfiltration in debittering process of spent brewer's
      yeast.
AB  - This study concerns the production of yeast extract from spent brewer's yeast
      using rotary microfiltration as a means to combine debittering and cell debris
      separation into a single step, without using a toxic alkali wash. The pH of yeast
      homogenate was found to affect protein yield and bitterness of the product.
      Rotary filtration of yeast homogenate at various pHs resulted in different
      percent protein transmissions. These were found to be 5.05%, 9.83%, and 30.83%
      for pH 5, 6, and 7.5, respectively. The bitterness concentration in the permeate
      was also found to be higher at higher pHs. Autolysis of the cell homogenate prior
      to filtration increased protein yield and decreased bitterness considerably. At
      pH 5.5, the protein transmission was increased to 60% and debittering efficiency
      was increased from 59% to 86%. The permeate flux and protein productivity could
      be further increased by increasing the rotational speed, but this resulted in a
      decrease in debittering efficiency. Thus, the rotational speed should be
      carefully selected to compromise between the yield and product quality.
      Furthermore, for the tested rotational speeds of 600 and 1000 rpm, the change in
      feed flow rate from 11 to 35 L h(-1) changes the flow behavior from turbulent
      vortex flow to laminar vortex flow, thus decreasing the flux and protein
      productivity.

PMID- 16084366
TI  - High yield of poly-gamma-glutamic acid from Bacillus subtilis by solid-state
      fermentation using swine manure as the basis of a solid substrate.
AB  - Solid-state fermentations (SSF), using swine manure as the basis of a solid
      substrate, were carried out for high yield of poly-gamma-glutamic acid (gamma
      PGA) by Bacillus subtilis CCTCC202048. Fermentation medium and process parameters
      were optimized through three orthogonal array designs. The optimal medium
      consisted of 62.3% (w/w, dry weight basis) swine manure, 25.0% soybean cake, 5.0%
      wheat bran, 5.0% glutamic acid, 2.5% citric acid and 0.2% MnSO4.H2O. The optimal
      process parameters were 15.0 g medium with initial moisture content 60% and
      initial pH 9.0 in 250 ml flask, inoculation at mid-log phase with a 4% inoculum
      level and cultivation for 48 h at 37 degrees C. The average-PGA yield (6.0%) in
      triplicate under optimal conditions was obtained on the laboratory scale while it
      was 4.5% at compost experiment. These would lay a foundation for lessening the
      pollution of swine manure, increasing fertilizer efficiency and exploring a late
      model organic fertilizer that retains water and nutrients.

PMID- 16084367
TI  - Rice husk filtrate as a nutrient medium for the growth of Desulfotomaculum
      nigrificans: characterisation and sulfate reduction studies.
AB  - The filtrate obtained by interacting a known amount of rice husk with deionised,
      Milli-Q water was assessed as a carbon source and nutrient medium for the growth
      of Desulfotomaculum nigrificans, a typical sulfate-reducing bacterium. The
      filtrate contained essential growth constituents such as magnesium, potassium,
      phosphorous apart from calcium, sodium, chloride and sulfate ions. Based on the
      1H and 13C NMR characterization studies, the organic composition of the
      components dissolved from the rice husk, was found to be: (i) 66% lignocellulosic
      material, (ii) 24% xylose+arabinose and (iii) 10% galactose. The growth studies
      indicated a 15-fold increase in the bacterial cell number in about 20 days.
      Nearly 81% and 66% reduction in sulfate concentration could be achieved in about
      28 days, from the solutions containing initial sulfate concentrations of 550 mg/l
      and 1200 mg/l respectively. In both the cases studied, the iron concentration
      could be reduced by over 85%.

PMID- 16084368
TI  - A two-step acid-catalyzed process for the production of biodiesel from rice bran
      oil.
AB  - A study was undertaken to examine the effect of temperature, moisture and storage
      time on the accumulation of free fatty acid in the rice bran. Rice bran stored at
      room temperature showed that most triacylglyceride was hydrolyzed and free fatty
      acid (FFA) content was raised up to 76% in six months. A two-step acid-catalyzed
      methanolysis process was employed for the efficient conversion of rice bran oil
      into fatty acid methyl ester (FAME). The first step was carried out at 60 degrees
      C. Depending on the initial FFA content of oil, 55-90% FAME content in the
      reaction product was obtained. More than 98% FFA and less than 35% of TG were
      reacted in 2 h. The organic phase of the first step reaction product was used as
      the substrate for a second acid-catalyzed methanolysis at 100 degrees C. By this
      two-step methanolysis reaction, more than 98% FAME in the product can be obtained
      in less than 8 h. Distillation of reaction product gave 99.8% FAME (biodiesel)
      with recovery of more than 96%. The residue contains enriched nutraceuticals such
      as gamma-oryzanol (16-18%), mixture of phytosterol, tocol and steryl ester (19
      21%).

PMID- 16084369
TI  - Aerobic nitrification-denitrification by heterotrophic Bacillus strains.
AB  - Twenty-four Bacillus strains predominantly outgrown in a night soil treatment
      system were isolated and characterized. Under various culture conditions, cell
      interactions took place among them and cell population changed. Maximum removal
      of NH4+-N and cell production by the isolates occurred under the conditions of
      30% DO and C/N ratio of 8. Five dominant isolates were identified to be species
      of Bacillus cereus, Bacillus subtilis and Bacillus licheniformis with
      similarities of 78-94%. Additions of 0.8% peptone and 0.3% yeast extract to a
      basal medium influenced the growth of isolates and the removal of NH4+-N in flask
      culture. Metal ions such as Ca2+, Fe2+ and Mg2+ had a similar effect. The
      specific growth rates of the five isolates were found to be in a range of 0.43
      0.55 h(-1). During the flask experiment of nitrogen removal under aerobic growth
      conditions, active nitrification by the isolates occurred largely in 1h with a
      decrease of COD and alkalinity reduced to only 74.6% of theoretical value. From
      the nitrogen balance, the percentage of nitrogen lost in the flask culture was
      estimated to be 33.0%, which was presumed to convert to N2 gas. This conversion
      of ammonia to N2 without formation of nitrous oxide under aerobic growth
      conditions was confirmed by GC analysis. From all the results, it has been found
      that the Bacillus strains were able to occur simultaneously aerobic
      nitrification/denitrification and the B3 process using the Bacillus strains
      seemed to possess some economic advantages.

PMID- 16084370
TI  - Hydrogen generation via anaerobic fermentation of paper mill wastes.
AB  - The objective of this work was to determine the hydrogen production from paper
      mill wastes using microbial consortia of solid substrate anaerobic digesters.
      Inocula from mesophilic, continuous solid substrate anaerobic digestion (SSAD)
      reactors were transferred to small lab scale, batch reactors. Milled paper (used
      as a surrogate paper waste) was added as substrate and acetylene or 2
      bromoethanesulfonate (BES) was spiked for methanogenesis inhibition. In the first
      phase of experiments it was found that acetylene at 1% v/v in the headspace was
      as effective as BES in inhibiting methanogenic activity. Hydrogen gas accumulated
      in the headspace of the bottles, reaching a plateau. Similar final hydrogen
      concentrations were obtained for reactors spiked with acetylene and BES. In the
      second phase of tests the headspace of the batch reactors was flushed with
      nitrogen gas after the first plateau of hydrogen was reached, and subsequently
      incubated, with no further addition of inhibitor nor substrate. It was found that
      hydrogen production resumed and reached a second plateau, although somewhat lower
      than the first one. This procedure was repeated a third time and an additional
      amount of hydrogen was obtained. The plateaux and initial rates of hydrogen
      accumulation decreased in each subsequent incubation cycle. The total cumulative
      hydrogen harvested in the three cycles was much higher (approx. double) than in
      the first cycle alone. We coined this procedure as IV-SSAH (intermittently vented
      solid substrate anaerobic hydrogen generation). Our results point out to a
      feasible strategy for obtaining higher hydrogen yields from the fermentation of
      industrial solid wastes, and a possible combination of waste treatment processes
      consisting of a first stage IV-SSAH followed by a second SSAD stage. Useful
      products of this approach would be hydrogen, organic acids or methane, and
      anaerobic digestates that could be used as soil amenders after post-treatment.

PMID- 16084371
TI  - Simultaneous nitrification and formaldehyde biodegradation in an activated sludge
      unit.
AB  - The simultaneous removal of formaldehyde and ammonium in a lab-scale activated
      sludge unit was investigated. The unit was operated at a hydraulic retention time
      of 2.4 days with an ammonium concentration in the influent of 350 mg NH4+-N/L,
      maintaining the ammonium loading rate at 0.15 g NH4+-N/Ld during the operation
      time. However, the applied organic loading rate was increased stepwise by
      increasing the formaldehyde concentration from 26 up to 3168 mg/L, corresponding
      to 0.01-1.40 g COD/Ld. High formaldehyde removal efficiencies, around 99.5% (+/
      0.38), were maintained at all the formaldehyde concentrations. Ammonium removal
      was also very high during the operation period, around 99.9% (+/-0.01). The
      ammonium concentration in the effluent was lower than 0.1 mg NH4+-N/L at all
      applied organic loading rates, indicating that there was no inhibition of
      nitrification by formaldehyde.

PMID- 16084372
TI  - Use of jute processing wastes for treatment of wastewater contaminated with dye
      and other organics.
AB  - A study was conducted to examine the potential of jute processing waste (JPW) for
      the treatment of wastewater contaminated with dye and other organics generated
      from various activities associated with jute cultivation and fibre production.
      Adsorption studies in batch mode have been conducted using dye solution as an
      adsorbate and JPW as an adsorbent. A comparative adsorption study was made with
      standard adsorbents such as powdered and granular activated carbon (PAC and GAC,
      respectively). A maximum removal of 81.7% was obtained with methylene blue dye
      using JPW as compared to 61% using PAC and 40% using GAC under similar
      conditions. The adsorption potential of JPW was observed to be dependent on
      various parameters such as type of dye, initial dye concentration, pH and dosage
      of adsorbent. The batch sorption data conformed well to the Langmuir and
      Freundlich isotherms. However, lower BOD (33.3%) and COD (13.8%) removal from
      retting effluent was observed using JPW as compared to 75.6% BOD removal and
      71.1% COD removal obtained with GAC.

PMID- 16084373
TI  - Preparation of carbon molecular sieves by carbon deposition from methane.
AB  - To prepare carbon molecular sieves (CMSs), methane was pyrolyzed in an attempt to
      deposit fine carbon particles on the micropore mouths of the carbon substrates
      being heated; the carbon substrates included grain-based activated carbons and
      commercial activated carbons. To explore the effects of heat treatment alone,
      blank experiments were conducted by heating the samples in N2. The resultant
      products were characterized by N2-adsorption at 77K. Methane failed to deposit
      carbon at 800 degrees C. The porosity of activated carbons, however, was
      substantially influenced by heat treatment alone. The surface areas and micropore
      volumes of the activated carbons from grain sorghum decreased by 39.32% and
      36.84%, respectively, upon heat treatment alone; this is attributable to the
      destruction of pore structure by sintering. In contrast, the corresponding values
      of the commercial activated carbons increased by 59.86% and 62.16%, respectively,
      upon heat treatment alone; this can be attributable to the development of
      microporosity.

PMID- 16084374
TI  - Fungal treatment of a delignification effluent from a nitrocellulose industry.
AB  - Twelve strains of filamentous fungi, most of them belonging to the Deuteromycetes
      class, were isolated from activated sludge adapted to the delignification
      effluent from a nitrocellulose industry and screened to be used in the treatment
      of the effluent. The screening experiment was carried out using the effluent
      without co-substrate, treated for 120 h and pH 5. Aspergillus 2BNL1, Aspergillus
      1AAL1 and Lentinus edodes UEC 2019 showed the highest effluent color reduction
      rates between 83% and 95%. The white-rot fungus L. edodes UEC 2019 was used as
      the control for the decolorization. In addition to color reduction, total phenol
      was also reduced in 56% and 79% by Aspergillus 2BNL1 and L. edodes UEC 2019,
      respectively. A kinetic experiment showed that Aspergillus 2BNL1 and Aspergillus
      1AAL1 reduced the effluent color in the range of 81-95% at the first 24 h while
      L. edodes required 72 h to achieve a similar result. UV/Visible spectra revealed
      that all fungi treatments were able to decrease the chromophore compounds present
      in the effluent, except Aspergillus 1AAL1 that increased the UV absorptions. The
      molar weight distribution analysis showed that the three fungi were able to
      change the pattern of the effluent chromatogram, probably by degradation of the
      high molecular weight compounds.

PMID- 16084375
TI  - An economic analysis of using alternative fuels in a mass burn boiler.
AB  - In this study the economic feasibility of using alternative fuels in a mass burn
      boiler for a chemical plant in northeastern Missouri is analyzed. The key
      consideration is whether biomass (switchgrass and crop residues) is economically
      preferred to other available fuels. Research reveals an abundance of alternative
      fuels for which the plant would receive a tipping fee, including municipal solid
      waste and used tires. Since the plant would have to pay for biomass, it does not
      appear in the optimal solution. An economic optimization model shows the marginal
      cost to the plant of using biomass would increase as more biomass is used,
      displacing quantities of more valuable (in terms of tipping fees per BTU) waste
      materials.

PMID- 16084376
TI  - Effects of a soil conditioner on some physical and biological features of soils:
      results from a greenhouse study.
AB  - A soil amendment substance-organic bio-stimulator, Terralyt Plus (TP), was used
      to observe its impact on the properties of clay loam (CL), sandy clay loam (SCL)
      and sandy loam (SL) soils and the growth of corn (Zea mays indentata L.) and
      wheat (Triticum aestivum ssp./vulgare Vill. v. lutescens) under greenhouse
      conditions. The diluted TP solutions (1:500, 1:1000 and 1:2000) were sprayed onto
      the soil surfaces. The wheat growth increased for CL and SCL with the application
      of TP at 1:1000. The highest dry weights were detected with 1:500 TP and corn in
      all the soils. Penetration resistance of CL containing corn increased with
      increasing TP concentration. TP was also effective in improving the aggregate
      stability for CL but not for the other soils. Catalase enzyme activity (CEA),
      soil evolution (SE) and the total aerobic bacterial population (TABP) were
      significantly increased (P<0.05) by spraying TP at 1:1000 onto CL.

PMID- 16084377
TI  - Production of mesoscopically patterned cellulose film.
AB  - Honeycomb and stripe patterned films were prepared from cellulose triacetate
      (CTA)/chloroform solution, as a result of the self-organization of the polymer
      during evaporation of the solvent. The honeycomb patterned CTA films were
      prepared by two methods, a direct pattern formation method and a transcription
      method. The latter method gave a well-organized microporous honeycomb pattern.
      Both types of patterned CTA films were saponified to yield the corresponding
      patterned cellulose films.

PMID- 16084378
TI  - Allostery trumps antibiotic resistance.

PMID- 16084379
TI  - A GLYmmer of insight into fibril formation.

PMID- 16084380
TI  - Bending and cutting forks and flaps.

PMID- 16084381
TI  - Bend to open?

PMID- 16084382
TI  - Inactivation and activity of cholesterol-dependent cytolysins: what structural
      studies tell us.
AB  - The homologous bacterially expressed cholesterol-dependent cytolysins (CDCs) form
      pores via oligomerization; this must occur preferentially once the target
      membrane has been engaged. Conformational changes in CDCs then drive partition
      from an aqueous environment to a lipidic one. This review addresses how premature
      oligomerization is prevented, how conformational changes are triggered, and how
      cooperativity between subunits brings about new functionality absent from
      isolated protomers. Variations are found in the answers provided by the CDCs to
      these issues. Some toxins use pH as a trigger of activity, but recent results
      have shown that dimerization in solution is an alternative way of preventing
      premature oligomerization, in particular for the CDC from Clostridium
      perfringens, perfringolysin. More controversially, there is still no resolution
      to the debate as to whether incomplete (arciform) oligomers form pores: recent
      results again suggest that they do.

PMID- 16084383
TI  - What makes an aquaporin a glycerol channel? A comparative study of AqpZ and GlpF.
AB  - The recent availability of high-resolution structures of two structurally highly
      homologous, but functionally distinct aquaporins from the same species, namely
      Escherichia coli AqpZ, a pure water channel, and GlpF, a glycerol channel,
      presents a unique opportunity to understand the mechanism of substrate
      selectivity in these channels. Comparison of the free energy profile of glycerol
      conduction through AqpZ and GlpF reveals a much larger barrier in AqpZ (22.8
      kcal/mol) than in GlpF (7.3 kcal/mol). In either channel, the highest barrier is
      located at the selectivity filter. Analysis of substrate-protein interactions
      suggests that steric restriction of AqpZ is the main contribution to this large
      barrier. Another important difference is the presence of a deep energy well at
      the periplasmic vestibule of GlpF, which was not found in AqpZ. The latter
      difference can be attributed to the more pronounced structural asymmetry of GlpF,
      which may play a role in attracting glycerol.

PMID- 16084384
TI  - The molecular origins of specificity in the assembly of a multienzyme complex.
AB  - The pyruvate dehydrogenase (PDH) multienzyme complex is central to oxidative
      metabolism. We present the first crystal structure of a complex between pyruvate
      decarboxylase (E1) and the peripheral subunit binding domain (PSBD) of the
      dihydrolipoyl acetyltransferase (E2). The interface is dominated by a "charge
      zipper" of networked salt bridges. Remarkably, the PSBD uses essentially the same
      zipper to alternately recognize the dihydrolipoyl dehydrogenase (E3) component of
      the PDH assembly. The PSBD achieves this dual recognition largely through the
      addition of a network of interfacial water molecules unique to the E1-PSBD
      complex. These structural comparisons illuminate our observations that the
      formation of this water-rich E1-E2 interface is largely enthalpy driven, whereas
      that of the E3-PSBD complex (from which water is excluded) is entropy driven.
      Interfacial water molecules thus diversify surface complementarity and contribute
      to avidity, enthalpically. Additionally, the E1-PSBD structure provides insight
      into the organization and active site coupling within the approximately 9 MDa PDH
      complex.

PMID- 16084385
TI  - Allosteric inhibition of aminoglycoside phosphotransferase by a designed ankyrin
      repeat protein.
AB  - Aminoglycoside phosphotransferase (3')-IIIa (APH) is a bacterial kinase that
      confers antibiotic resistance to many pathogenic bacteria and shares structural
      homology with eukaryotic protein kinases. We report here the crystal structure of
      APH, trapped in an inactive conformation by a tailor-made inhibitory ankyrin
      repeat (AR) protein, at 2.15 A resolution. The inhibitor was selected from a
      combinatorial library of designed AR proteins. The AR protein binds the C
      terminal lobe of APH and thereby stabilizes three alpha helices, which are
      necessary for substrate binding, in a significantly displaced conformation.
      BIAcore analysis and kinetic enzyme inhibition experiments are consistent with
      the proposed allosteric inhibition mechanism. In contrast to most small-molecule
      kinase inhibitors, the AR proteins are not restricted to active site binding,
      allowing for higher specificity. Inactive conformations of pharmaceutically
      relevant enzymes, as can be elucidated with the approach presented here,
      represent powerful starting points for rational drug design.

PMID- 16084386
TI  - Glycine residues appear to be evolutionarily conserved for their ability to
      inhibit aggregation.
AB  - Six glycine residues of human muscle acylphosphatase (AcP) are evolutionarily
      conserved across the three domains of life. We have generated six variants of
      AcP, each having a glycine substituted by an alanine (G15A, G19A, G37A, G45A,
      G53A, and G69A). Three additional variants had Gly45 replaced by serine,
      glutamate, and arginine, respectively. The mutational variants do not, on
      average, have a lower conformational stability than other variants with
      substitutions of nonconserved residues. In addition, only the G15A variant is
      enzymatically inactive. However, all variants, with the exception of the G15A
      mutant, form amyloid aggregates more rapidly than the wild-type. Dynamic light
      scattering experiments carried out under conditions close to physiological
      confirm that aggregate formation is generally more pronounced for the glycine
      substituted variants. Apart from the glycine at position 15, all other conserved
      glycine residues in this protein could have been maintained during evolution
      because of their ability to inhibit aggregation.

PMID- 16084387
TI  - Additivity in both thermodynamic stability and thermal transition temperature for
      rubredoxin chimeras via hybrid native partitioning.
AB  - Given any operational definition of pairwise interaction, the set of residues
      that differ between two structurally homologous proteins can be uniquely
      partitioned into subsets of clusters for which no such interactions occur between
      clusters. Although hybrid protein sequences that preserve such clustering are
      consistent with tertiary structures composed of only parental native-like
      interactions, the stability of such predicted structures will depend upon the
      physical robustness of the assumed interaction potential. A simple distance
      cutoff criterion was applied to the most thermostable protein known to predict
      such a seven-residue cluster in the metal binding site region of Pyrococcus
      furiosus rubredoxin and a mesophile homolog. Both conformational stability and
      thermal transition temperature measurements demonstrate that 39% of the
      differential stability arises from these seven residues.

PMID- 16084388
TI  - Atomic models by cryo-EM and site-directed spin labeling: application to the N
      terminal region of Hsp16.5.
AB  - We report an approach for determining the structure of macromolecular assemblies
      by the combined application of cryo-electron microscopy (cryo-EM) and site
      directed spin labeling electron paramagnetic resonance spectroscopy (EPR). This
      approach is illustrated for Hsp16.5, a small heat shock protein that prevents the
      aggregation of nonnative proteins. The structure of Hsp16.5 has been previously
      studied by both cryo-EM and X-ray crystallography. The crystal structure revealed
      a roughly spherical protein shell with dodecameric symmetry; however, residues 1
      32 were found to be disordered. The cryo-EM reconstruction at 13 A resolution
      appeared similar to the crystal structure but with additional internal density
      corresponding to the N-terminal regions of the 24 subunits. In this study, a
      systematic application of site-directed spin labeling and EPR spectroscopy was
      carried out. By combining the EPR constraints from spin label accessibilities and
      proximities with the cryo-EM density, we obtained an atomic model for a portion
      of the Hsp16.5 N-terminal region in the context of the oligomeric complex.

PMID- 16084389
TI  - Conferring substrate specificity to DNA helicases: role of the RecQ HRDC domain.
AB  - RecQ DNA helicases are multidomain enzymes that play pivotal roles in genome
      maintenance pathways. While the ATPase and helicase activities of these enzymes
      can be attributed to the conserved catalytic core domain, the role of the
      Helicase-and-RNase-D-C-terminal (HRDC) domain in RecQ function has yet to be
      elucidated. Here, we report the crystal structure of the E. coli RecQ HRDC
      domain, revealing a globular fold that resembles known DNA binding domains. We
      show that this domain preferentially binds single-stranded DNA and identify its
      DNA binding surface. HRDC domain mutations in full-length RecQ lead to surprising
      differences in its structure-specific DNA binding properties. These data support
      a model in which naturally occurring variations in DNA binding residues among
      diverse RecQ homologs serve to target these enzymes to distinct substrates and
      provide insight into a mechanism whereby RecQ enzymes have evolved distinct
      functions in organisms that encode multiple recQ genes.

PMID- 16084390
TI  - Structural and functional analyses of an archaeal XPF/Rad1/Mus81 nuclease:
      asymmetric DNA binding and cleavage mechanisms.
AB  - XPF/Rad1/Mus81/Hef proteins recognize and cleave branched DNA structures. XPF and
      Rad1 proteins cleave the 5' side of nucleotide excision repair bubble, while
      Mus81 and Hef cleave similar sites of the nicked Holliday junction, fork, or flap
      structure. These proteins all function as dimers and consist of catalytic and
      helix-hairpin-helix DNA binding (HhH) domains. We have determined the crystal
      structure of the HhH domain of Pyrococcus furiosus Hef nuclease (HefHhH), which
      revealed the distinct mode of protein dimerization. Our structural and
      biochemical analyses also showed that each of the catalytic and HhH domains binds
      to distinct regions within the fork-structured DNA: each HhH domain from two
      separate subunits asymmetrically binds to the arm region, while the catalytic
      domain binds near the junction center. Upon binding to DNA, Hef nuclease disrupts
      base pairs near the cleavage site. It is most likely that this bipartite binding
      mode is conserved in the XPF/Rad1/Mus81 nuclease family.

PMID- 16084391
TI  - NMR structural characterization and computational predictions of the major
      intermediate in oxidative folding of leech carboxypeptidase inhibitor.
AB  - The III-A intermediate constitutes the major rate-determining step in the
      oxidative folding of leech carboxypeptidase inhibitor (LCI). In this work, III-A
      has been directly purified from the folding reaction and structurally
      characterized by NMR spectroscopy. This species, containing three native
      disulfides, displays a highly native-like structure; however, it lacks some
      secondary structure elements, making it more flexible than native LCI. III-A
      represents a structurally determined example of a disulfide-insecure
      intermediate; direct oxidation of this species to the fully native protein seems
      to be restricted by the burial of its two free cysteine residues inside a native
      like structure. We also show that theoretical approaches based on topological
      constraints predict with good accuracy the presence of this folding intermediate.
      Overall, the derived results suggest that, as it occurs with non-disulfide bonded
      proteins, native-like interactions between segments of secondary structure rather
      than the crosslinking of disulfide bonds direct the folding of LCI.

PMID- 16084393
TI  - Connecting the protein structure universe by using sparse recurring fragments.
AB  - The quest to order and classify protein structures has lead to various
      classification schemes, focusing mostly on hierarchical relationships between
      structural domains. At the coarsest classification level, such schemes typically
      identify hundreds of types of fundamental units called folds. As a result, we
      picture protein structure space as a collection of isolated fold islands. It is
      obvious, however, that many protein folds share structural and functional
      commonalities. Locating those commonalities is important for our understanding of
      protein structure, function, and evolution. Here, we present an alternative view
      of the protein fold space, based on an interfold similarity measure that is
      related to the frequency of fragments shared between folds. In this view, protein
      structures form a complicated, crossconnected network with very interesting
      topology. We show that interfold similarity based on sequence/structure fragments
      correlates well with similarities of functions between protein populations in
      different folds.

PMID- 16084392
TI  - The pore structure of the closed RyR1 channel.
AB  - Using single particle electron cryomicroscopy, several helices in the membrane
      spanning region of RyR1, including an inner transmembrane helix, a short pore
      helix, and a helix parallel to the membrane on the cytoplasmic side, have been
      clearly resolved. Our model places a highly conserved glycine (G4934) at the
      hinge position of the bent inner helix and two rings of negative charges at the
      luminal and cytoplasmic mouths of the pore. The kinked inner helix closely
      resembles the inner helix of the open MthK channel, suggesting that kinking alone
      does not open RyR1, as proposed for K+ channels.

PMID- 16084394
TI  - Nucleotide-induced DNA polymerase active site motions accommodating a mutagenic
      DNA intermediate.
AB  - DNA polymerases occasionally insert the wrong nucleotide. For this error to
      become a mutation, the mispair must be extended. We report a structure of DNA
      polymerase beta (pol beta) with a DNA mismatch at the boundary of the polymerase
      active site. The structure of this complex indicates that the templating adenine
      of the mispair stacks with the primer terminus adenine while the templating
      (coding) cytosine is flipped out of the DNA helix. Soaking the crystals of the
      binary complex with dGTP resulted in crystals of a ternary substrate complex. In
      this case, the templating cytosine is observed within the DNA helix and forms
      Watson-Crick hydrogen bonds with the incoming dGTP. The adenine at the primer
      terminus has rotated into a syn-conformation to interact with the opposite
      adenine in a planar configuration. Yet, the 3'-hydroxyl on the primer terminus is
      out of position for efficient nucleotide insertion.

PMID- 16084395
TI  - SUMO fusion technology for difficult-to-express proteins.
AB  - The demands of structural and functional genomics for large quantities of
      soluble, properly folded proteins in heterologous hosts have been aided by
      advancements in the field of protein production and purification. Escherichia
      coli, the preferred host for recombinant protein expression, presents many
      challenges which must be surmounted in order to over-express heterologous
      proteins. These challenges include the proteolytic degradation of target
      proteins, protein misfolding, poor solubility, and the necessity for good
      purification methodologies. Gene fusion technologies have been able to improve
      heterologous expression by overcoming many of these challenges. The ability of
      gene fusions to improve expression, solubility, purification, and decrease
      proteolytic degradation will be discussed in this review. The main disadvantage,
      cleaving the protein fusion, will also be addressed. Focus will be given to the
      newly described SUMO fusion system and the improvements that this technology has
      advanced over traditional gene fusion systems.

PMID- 16084396
TI  - Improved yields for baculovirus-mediated expression of human His(6)-PDK1 and
      His(6)-PKBbeta/Akt2 and characterization of phospho-specific isoforms for design
      of inhibitors that stabilize inactive conformations.
AB  - PDK1 and PKB/Akt have a pleckstrin homology (PH) domain at the C-terminus and N
      terminus, respectively, which stabilizes an unphosphorylated, autoinhibited
      conformation. Binding of the PH domain to a phospholipid second messenger causes
      relief of autoinhibition, which results in kinase phosphorylation and activation.
      Baculovirus-mediated expression in Sf9 insect cells of both His(6)-PDK1 and
      His(6)-PKBbeta/Akt2 were optimized, which significantly improved the yields (5
      fold) of the affinity purified enzymes over previously reported values.
      Isoelectric focusing (IEF) and Western analyses indicated that the apparent
      V(max)=192+/-13 U/mg and K(m) (PDK-Tide)=55+/-10 microM of purified His(6)-PDK1
      results from a mixture of at least three different phospho-specific isoforms (pI
      values of 6.8, 6.5, and 6.4). A purely unphosphorylated isoform of His(6)-PDK1
      (pI=6.8) was generated by treatment with lambda protein phosphatase (lambdaPP),
      which decreased V(max) to 2.4+/-0.4 U/mg and increased K(m) (PDK-Tide) to 217+/
      61 microM. Isoelectric focusing and Western analyses indicated that the apparent
      V(max)=0.21+/-0.03 U/mg and K(m) (Crosstide)=87+/-30 microM of purified His(6)
      PKBbeta/Akt2 results from a mixture of the enzyme monophosphorylated either at
      Ser-474 ( approximately 90%) or at Thr-309 ( approximately 10%). A purely
      unphosphorylated isoform of His(6)-PKBbeta/Akt2 (pI=6.4) was generated by
      treatment with lambdaPP, which decreased V(max) approximately 2-fold. The
      optimization of high-level production and detailed characterization of purified
      and lambdaPP-treated His(6)-PDK1 and His(6)-PKBbeta/Akt2 will facilitate detailed
      structural and kinetic studies aimed at understanding the mechanism of second
      messenger-induced activation.

PMID- 16084397
TI  - Cloning, high yield overexpression, purification, and characterization of AlgH, a
      regulator of alginate biosynthesis in Pseudomonas aeruginosa.
AB  - The most common cause of mortality among cystic fibrosis sufferers is infection
      by antibiotic resistant strains of Pseudomonas aeruginosa. Means to control these
      strains continue to be an important goal. An integral component of the ability of
      many of these strains to defy antibiotic therapies is the protection afforded by
      the mucoexopolysaccharide alginate. Production of alginate by P. aeruginosa is
      tightly regulated at the transcriptional level. AlgH, a putative transcriptional
      regulator, is involved in regulating alginate biosynthesis as well as nucleoside
      diphosphate kinase activity and succinyl coenzyme A synthetase activity in P.
      aeruginosa. Sequence homologues are found in many bacterial species. Here, we
      describe a method for high level overexpression and high yield/high purity
      production of AlgH for biophysical and functional studies. The algH gene was
      cloned and AlgH was overexpressed in Escherichia coli using a commercially
      available vector with an inducible T7 promoter. We purified the recombinantly
      produced protein using a rapid classical purification scheme. The yield of
      purified protein, either isotopically labeled for NMR studies or unlabeled, is
      excellent (30-37 mg of purified protein per liter of minimal media culture), as
      is the purity (>95% pure). Analysis of the secondary structure using circular
      dichroism and NMR indicates that the protein is comprised of both beta-sheet and
      alpha-helical secondary structural elements. Heteronuclear NMR spectra indicate
      that AlgH is a monodisperse, folded globular protein. This rapid, high yield, and
      high purity method for AlgH production will permit further biophysical
      characterization of this protein including high resolution structural studies.

PMID- 16084398
TI  - Cloning, expression, characterization, and crystallization of a glutaminyl
      cyclase from human bone marrow: a single zinc metalloenzyme.
AB  - Glutaminyl cyclase (QC) catalyzes the N-terminal pyroglutamate formation of
      numerous hormones and peptides from their glutaminyl precursor. Pyroglutamate is
      a posttranslational or cotranslational modification important in many
      physiological and pathological processes. Here, we present the cloning of a QC
      cDNA from human bone marrow cDNA library. The protein was expressed in
      Escherichia coli system with the yields higher than approximately 10 mg/L
      bacterial culture, using a thioredoxin-tagged expression vector with several
      modifications. Based on high histidine content ( approximately 5%) of the
      protein, a convenient purification step by Ni-affinity chromatography was
      designed, leading to near homogeneity of the purified human QC. The identity of
      the recombinant human QC was confirmed by mass spectrometry and circular
      dichroism spectroscopy. The enzyme was active on both synthetic and physiological
      substrates, and the activity could be inhibited by several imidazole, triazole,
      and tetrazole derivatives. An atomic absorption analysis demonstrated that human
      QC contains one zinc ion per protein molecule. We also obtained the human QC
      crystals, which belong to cubic, tetragonal, and rhombohedral forms. Our works
      are useful to acquire new insights into human and animal QCs, particularly for
      future structural analysis and inhibitor designs.

PMID- 16084400
TI  - Intestinal innate immunity: how does it relate to the pathogenesis of necrotizing
      enterocolitis.
AB  - The pathogenesis of necrotizing enterocolitis (NEC) is poorly understood, but
      appears to be multifactorial and highly associated with immaturity of the
      gastrointestinal tract, colonization of the intestinal microbiota, and immature
      innate immune system. The goal of this review is to provide an overview of some
      of these risk factors and how they might lead to the genesis of NEC. A better
      understanding of these factors should help us prevent and treat this devastating
      disease.

PMID- 16084401
TI  - The role of PAF, TLR, and the inflammatory response in neonatal necrotizing
      enterocolitis.
AB  - The pathogenesis of neonatal necrotizing enterocolitis remains poorly understood.
      Recent evidence suggests that PAF (platelet activating factor) and human toll
      like receptors (TLRs) contribute to the pro-inflammatory response that is
      characteristic of NEC pathology. Understanding the regulation of these molecular
      interactions may provide new approaches for prevention or treatment of this
      dreaded condition.

PMID- 16084402
TI  - Ischemia and necrotizing enterocolitis: where, when, and how.
AB  - While it is accepted that ischemia contributes to the pathogenesis of necrotizing
      enterocolitis (NEC), three important questions regarding this role subsist.
      First, where within the intestinal circulation does the vascular pathophysiology
      occur? It is most likely that this event begins within the intramural
      microcirculation, particularly the small arteries that pierce the gut wall and
      the submucosal arteriolar plexus insofar as these represent the principal sites
      of resistance regulation in the gut. Mucosal damage might also disrupt the
      integrity or function of downstream villous arterioles leading to damage thereto;
      thereafter, noxious stimuli might ascend into the submucosal vessels via
      downstream venules and lymphatics. Second, when during the course of pathogenesis
      does ischemia occur? Ischemia is unlikely to the sole initiating factor of NEC;
      instead, it is more likely that ischemia is triggered by other events, such as
      inflammation at the mucosal surface. In this context, it is likely that ischemia
      plays a secondary, albeit critical role in disease extension. Third, how does the
      ischemia occur? Regulation of vascular resistance within newborn intestine is
      principally determined by a balance between the endothelial production of the
      vasoconstrictor peptide endothelin-1 (ET-1) and endothelial production of the
      vasodilator free radical nitric oxide (NO). Under normal conditions, the balance
      heavily favors NO-induced vasodilation, leading to a low resting resistance and
      high rate of flow. However, factors that disrupt endothelial cell function, eg,
      ischemia-reperfusion, sustained low-flow perfusion, or proinflammatory mediators,
      alter the ET-1:NO balance in favor of constriction. The unique ET-1-NO
      interaction thereafter might facilitate rapid extension of this constriction,
      generating a viscous cascade wherein ischemia rapidly extends into larger
      portions of the intestine.

PMID- 16084403
TI  - Mechanisms of nitric oxide-mediated intestinal barrier failure in necrotizing
      enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is the leading intestinal emergency in premature
      infants. The underlying etiology of NEC remains elusive, but hypoxic conditions
      and early enteral feeding are consistently implicated as the main risk factors in
      the pathogenesis of NEC. We postulate that nitric oxide (NO) plays a key role as
      a molecular signaling "hub" in the generation of gut barrier failure in NEC.
      Clinical studies suggest that inflammatory cytokines and excessive NO production
      may contribute to the pathogenesis of NEC. One of the major challenges in
      defining the critical signaling pathways that lead to the development of NEC is
      the lack of specific biochemical markers that consistently delineate the early
      stages of NEC. Intestinal pathology and molecular markers derived from late-stage
      NEC represent end-stage findings and thus provide little insight into the early
      events that led to intestinal inflammation. Such markers may not represent viable
      therapeutic targets for the treatment or prevention of NEC. Therefore, novel
      strategies are needed to identify the patients at risk for NEC and define the
      clinically relevant molecules that characterize the early stages of NEC. This
      review will examine the mechanisms of NO-mediated gut barrier failure and propose
      novel genetic-based approaches for elucidating the critical molecular pathways in
      NEC.

PMID- 16084404
TI  - Heparin-binding EGF-like growth factor (HB-EGF) and necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal
      disease that occurs predominantly in premature infants. Despite various advances
      in management, the mortality of this disease remains high. During the last
      decade, studies from our laboratory have shown that heparin-binding epidermal
      growth factor-like growth factor (HB-EGF), a member of the epidermal growth
      factor (EGF) family, can protect intestinal epithelial cells (IEC) from various
      forms of injury in vitro. Furthermore, we have used both an intestinal I/R injury
      model in adult rats, and a neonatal rat pup model of NEC, to show that HB-EGF can
      protect the intestines from injury. On administration of HB-EGF in the neonatal
      rat model, the incidence of NEC is reduced from 65% to 27.3% (P < 0.05), and the
      histological injury score is decreased from 2 to 1.1 (P < 0.05). In addition, the
      survival rate is increased from 25% to 63.6% and the survival time extended from
      59 hours to 73 hours (P < 0.05). In addition, using human specimens from newborns
      undergoing bowel resection for NEC, we found that the expression of endogenous HB
      EGF mRNA in normal areas of the intestine at the resection margins was higher
      than that of the intestine afflicted with acute NEC. Endogenous HB-EGF may be
      involved in epithelial cell repair, proliferation, and regeneration during
      recovery from injury. Exogenous administration of HB-EGF potentiates recovery
      from intestinal injury in vitro and in vivo. Taken together, these results
      support a potential therapeutic role for HB-EGF in the treatment of NEC in the
      future.

PMID- 16084405
TI  - Role of epidermal growth factor in the pathogenesis of neonatal necrotizing
      enterocolitis.
AB  - Neonatal necrotizing enterocolitis (NEC) is an increasingly frequent condition
      encountered in premature infants for which the etiology is not well understood.
      Epidermal growth factor (EGF) is abundant in many fluids bathing the fetal and
      neonatal gastrointestinal tract, including amniotic fluid, saliva, and breast
      milk. EGF is acknowledged to be important for normal intestinal development as
      well as repair following injury to the gastrointestinal mucosa. There appears to
      be mounting evidence to support a possible link between deficient EGF production
      and the development of NEC. The relevant evidence for the role of EGF in
      intestinal development and mucosal repair, as well as its potential involvement
      in the genesis of NEC will be reviewed.

PMID- 16084406
TI  - Surgical therapy for necrotizing enterocolitis: bringing evidence to the bedside.
AB  - Necrotizing enterocolitis is the most common surgical emergency in the neonatal
      intensive care unit. Despite decades of research that have led to a growing
      knowledge base about this disease, NEC continues to challenge the pediatric
      surgeon. In this review, we will examine the development of surgical therapy for
      NEC in the context of the supportive evidence, or lack thereof, for treatment
      approaches. We will discuss issues of indications for surgical intervention,
      primary peritoneal drainage versus laparotomy, enterostomy versus primary
      anastamosis and issues surrounding NEC totalis.

PMID- 16084407
TI  - Operative strategies for necrotizing enterocolitis: The prevention and treatment
      of short-bowel syndrome.
AB  - Necrotizing enterocolitis (NEC) is the leading cause of short-bowel syndrome
      (SBS) in infancy. Studies on the acute medical and surgical management of NEC
      have traditionally focused on short-term morbidity and mortality, with less
      emphasis on long-term outcomes. Acute surgical management of NEC involves the
      often competing priorities of controlling sepsis and preserving bowel length.
      Bowel-preserving strategies for NEC, designed to limit SBS, are based on
      peritoneal drainage, limited resection, or a combination of both. Drainage-based
      strategies are generally favored in smaller neonates, while laparotomy-based
      strategies are favored in larger patients, especially those with a more limited
      extent of intestinal injury. Comparisons of drainage-based approaches and
      resection-based approaches are limited by confounding variables, and neither
      approach is clearly superior with regard to subsequent SBS. These traditional as
      well as more creative approaches to bowel preservation have application in NEC,
      yet they depend on a series of patient and treatment characteristics that include
      the ability of diseased but viable bowel to recover both absorptive and motility
      function after acute NEC, the ability of the infant to tolerate appropriately
      drained intraperitoneal contamination, and the ability of the injured intestine
      to subsequently undergo intestinal adaptive change. In addition, there are a
      series of operative options that have been designed to mitigate the impact of SBS
      once it is established. These procedures are not uniquely applied exclusively for
      NEC-induced SBS. However, strategies that slow intestinal transit, improve
      peristaltic function, or enhance mucosal absorptive function each have
      application in the management of SBS.

PMID- 16084409
TI  - The interventional MR imaging suite: magnet designs and equipment requirements.
AB  - Soon after the introduction of MR imaging as an imaging tool, researchers began
      to investigate its capabilities to guide interventional minimally invasive
      procedures, such as biopsies. These early efforts have encouraged vendors and
      numerous research groups worldwide to identify clinical problems in the field of
      image-guided intervention, for which MR imaging is beneficial as an imaging
      modality, and to develop and refine soft-ware and hardware components to meet the
      specific requirements of interventional MR imaging. Over nearly 20 years,
      continuous advances in magnet and system design have accelerated the progress of
      MR-guided intervention.

PMID- 16084410
TI  - Update to pulse sequences for interventional MR imaging.
AB  - The motivations for developing MR-guided minimally invasive therapy include its
      excellent soft tissue contrast, tomographic imaging in any direction (as opposed
      to projection imaging as in fluoroscopy), the absence of ionizing radiation,the
      abundance of contrast mechanisms (including bright blood pulse sequences that
      lead to excellent vessel conspicuity without exogenous contrast agent injection),
      the ability to obtain physiologic information such as perfusion, and an overall
      excellent safety profile. The main pulse sequences used today for interventional
      MR imaging are T1/T2-weighted FISP and TrueFISP, T2-weighted turbo spin-echo, and
      T1-weighted FLASH. The specific clinical question, the underlying
      pathophysiology,and the procedure to be performed dictate which sequence is used.
      Each of these sequences has been written to acquire data in conventional
      rectilinear trajectories, radial k-space paths, or even spirals. In many ways,
      the questions being researched in interventional MR imaging have been dictated by
      the primary issues in greatest need of resolution or that most directly
      facilitate new clinical development. A decade ago, research focused on
      exploration of new scan strategies for contrast and temporal resolution.
      Advancements in the last decade have made it possible to acquire and display
      greater than 10 images per second in realtime with millimeter resolution in all
      three directions. This temporal and spatial resolution is considered high enough
      to guide most interventions. With this capability, other research has focused on
      instrument tracking. The field has gone from the capability to track a single
      coil and superimpose it on a previously acquired roadmap to systems that follow,
      adapt, and provide high-resolution images due to the advent of multichannel
      receiver systems, improved graphics, higher processor speeds, and increases in
      speed and quantity of memory. Hence, instruments can be reliably identified and
      tracked and the information can be used to update pulse sequence parameters in
      real time, thereby opening new opportunities for interventional MR imaging that
      extend from biopsy and thermal therapy to image-guided vascular and cardiac
      procedures. Today, we see such issues as RF heating of wires used for device
      localization and the noise generated by rapid switching of MR gradients being
      significant obstacles yet to overcome to allow the full strength of MR-guided
      interventions to be realized clinically. It is anticipated that these topics will
      emerge as critical concepts in the next decade of interventional MR imaging
      research.

PMID- 16084411
TI  - MR-guided endovascular interventions: device visualization, tracking, navigation,
      clinical applications, and safety aspects.
AB  - Reliable visualization and tracking are essential for guiding endovascular
      devices within blood vessels. The most commonly used methods are susceptibility
      artifact-based tracking that relies on the artifact created within the image by
      the device and microcoil- or antenna-based tracking that uses the high signal
      generated by small MR endovascular receive coils when the transmit coil emits a
      nonselective radiofrequency pulse. To date, the use of endovascular MR guidance
      techniques has primarily been confined to animal experiments. There are only a
      few reports on MR-guided endovascular applications in patients. Therefore, access
      to the patient within the scanner, dedicated devices, and safety issues remain
      major challenges. To face these challenges, attention from all radiologists,
      especially interventional radiologists, is required to make MR-guided
      endovascular procedures a clinical reality.

PMID- 16084412
TI  - Percutaneous biopsy from blinded to MR guided: an update on current techniques
      and applications.
AB  - The advent of interventional MR imaging techniques as well as their adoption to
      guide percutaneous biopsies and aspirations has served as a further step along a
      series of technical refinements that commenced with the implementation of image
      guided approaches for tissue sampling. Nowadays, the practice of and the
      expectations from these procedures are quite different from those of the blind
      percutaneous thrusts performed in the late nineteenth and early twentieth
      centuries. As the field of interventional MR imaging continues to flourish and to
      attract more radiologists who realize the many opportunities that this technology
      can offer to their patients, there is a need for a full comprehension of the
      concepts, techniques, limitations, and cost-effectiveness of MR imaging guidance
      to present this service to clinical partners in the appropriate setting.
      Radiologists should also recognize the need for their significant involvement in
      the technical aspects of MR-guided procedures, because several user-defined
      parameters and trajectory decisions can alter device visualization in the MR
      imaging environment and hence affect procedure safety.

PMID- 16084413
TI  - Cardiovascular interventional MR imaging: a new road for therapy and repair in
      the heart.
AB  - Over the last 5 years, interventional MR imaging has been fertile ground for
      research. Real-time MR imaging, combined with recent advances in other MR imaging
      modalities such as perfusion imaging and intravascular imaging, has opened up new
      paths for cardiac therapy. The recent reports on cardiac stem cell therapy guided
      and monitored by MR imaging suggest that we are already seeing the establishment
      of an important role for cardiac MR imaging in cardiac restoration. The
      collaborative effort from a multidisciplinary team of basic biologists,
      engineers, and clinicians will refine stem cell incubation and labeling for MR
      guided transcatheter endomyocardial injections, and this in turn may facilitate
      new studies in humans. Several groups have demonstrated in animal studies the
      feasibility of MR-guided catheter interventions for the treatment of congenital
      heart disease and arrythmia therapy. Hence, applications in humans remain the
      challenge for the next years. Although there have been first reports of cardiac
      catheterizations in humans by combined use of x-ray fluoroscopy and MR imaging,
      there are no reports in the literature suggesting that active tracking methods by
      MR imaging have been applied to humans. Safety issues (namely, heating of
      catheters and wires) hamper clinical use, particularly in infants and children.
      Current reports are promising that these limitations will be overcome in the near
      future and will eventually reduce x-ray usage during catheterization. In its
      current state, cardiac MR imaging offers a unique opportunity to investigate new
      therapeutic strategies for the treatment of congenital and acquired heart
      disease.

PMID- 16084414
TI  - Intrabiliary MR imaging.
AB  - The goal of this research is to illustrate the potential role of interventional
      MR imaging ina clinical setting. As shown by this study, IBMR is feasible, is
      well tolerated, and positively affects patient management. IBMR allowed for
      significantly decreased field of view and high in-plane resolution and provided
      contrast between the biliary lumen and adjacent structures with high diagnostic
      accuracy. This technique enabled clinicians not only to improve imaging of the
      biliary tree but also to make a more accurate diagnosis. Based on this pilot
      work, there are several potential avenues of further expansion for IBMR. For
      example, enhanced imaging of the biliary tree may allow for monitoring of new
      biliary treatment regimens such as photodynamic therapy or molecular targeting.
      In addition, this technique may also foster development of innovative new
      percutaneous procedures that may eventually treat some biliary disorders under MR
      imaging guidance.

PMID- 16084415
TI  - MR-guided interventions for prostate cancer.
AB  - MR imaging is currently the most effective diagnostic imaging tool for
      visualizing the anatomy and pathology of the prostate gland. Currently, the
      practicality and cost effectiveness of transrectal ultrasound dominates image
      guidance for needle-based prostate interventions. Challenges to the integration
      of diagnostic and interventional MR imaging have included the lack of real-time
      feed-back, the complexity of the imaging technique, and limited access to the
      perineum within the geometric constraints of the MR imaging scanner. Two basic
      strategies have been explored and clinically demonstrated in the literature: (1)
      coregistration of previously acquired diagnostic MR imaging to interventional
      TRUS or open scanner MR images, and (2) stereotactic needle interventions within
      conventional diagnostic scanners using careful patient positioning or the aid of
      simple manipulators. Currently, researchers are developing techniques that render
      MR imaging the method of choice for the direct guidance of many procedures. This
      article focuses on needle-based interventions for prostate cancer, including
      biopsy, brachytherapy, and thermal therapy With rapid progress in biologic
      imaging of the prostate gland, the authors believe that MR imaging guidance will
      play an increasing role in the diagnosis and treatment of prostate cancer.

PMID- 16084416
TI  - MR-guided interventions of the breast.
AB  - Techniques and instrumentation are now widely available that enable
      interventional MR-guided preoperative needle localization and lesion marking.
      Minimally invasive MR-guided core biopsy techniques have been demonstrated but
      remain limited for small lesions and will be facilitated by the development of
      biopsy instruments that can be directly visualized using MR imaging. MR-guided
      tumor ablation is beginning to be evaluated in a few centers. It holds promise as
      new treatment modality in the continuing trend toward greater breast conservation
      in the local therapy of breast cancer. Further studies are needed to document the
      ability of MR-guided ablation to control the margins of a tumor as effectively as
      surgery. Patients with an extensive in situ intra-ductal component may pose a
      significant hurdle because the extent of ductal carcinoma in situ maybe
      underestimated on breast MR images. Ultimately, the success of MR-guided thermal
      ablation depends on the ability of MR imaging to map the extent of heating during
      the procedure so that the procedure can be performed to achieve complete control
      of the tumor margins. It is unfortunate that the conventional method for MR
      thermometry--the proton resonance frequency shift method--does not work in fat or
      in voxels with a mix of fat and glandular tissue and, hence, has limited
      applicability in the breast. Other methods, including measurement of T1 and T2,
      are being investigated as alternatives.

PMID- 16084417
TI  - Musculoskeletal interventional MR imaging.
AB  - MR imaging guidance has great potential to direct the management of diagnostic
      and therapeutic procedures performed in the musculoskeletal region. To take full
      advantage of this excellent diagnostic tool, radiologists should also embrace the
      minimally invasive techniques available for MR imaging. This can be achieved by
      cooperation with clinical colleagues, multidisciplinary integration, and the
      development of efficient techniques for MR-guided procedures. By combining the
      excellent ability to recognize pathologic findings and the feasibility of
      performing interventional procedures, MR imaging is emerging as a powerful tool
      in diagnosing and treating musculoskeletal neoplasms and in performing minimally
      invasive procedures, such as spine injections.

PMID- 16084418
TI  - Intraoperative MR imaging.
AB  - With the rapid evolution of technologic advances in neurosurgery, it is no
      surprise that the use of MR imaging to guide the performance of safe and
      effective surgical procedures is at the forefront of development. This article
      highlights the current capabilities of intraoperative MR-guided surgery for a
      variety of neurosurgical procedures and traces the evolution of the field to its
      present level of technical sophistication. The costs of intraoperative MR imaging
      and its future directions are discussed.

PMID- 16084419
TI  - MR imaging-controlled focused ultrasound ablation: a noninvasive image-guided
      surgery.
AB  - The history of MR-guided FUS demonstrates the need for merging advanced therapy
      technology with advanced imaging. Without the ability of MR imaging to localize
      the tumor margins and without the temperature-sensitive imaging that provides the
      closed-loop control of energy deposition, this method is inadequate for most
      clinical applications. Given these limitations,high-intensity focused ultrasound
      initially appeared to have a narrow application area and was not able to compete
      with other surgical or ablation methods. Today, MR imaging-guided FUS has become
      a safe and effective means of performing probe-delivered thermal ablations and
      minimally invasive surgery. Moreover, it has the potential to replace treatments
      that use ionizing radiation such as radiosurgery and brachytherapy. Although the
      cost of integrating"big ticket" MR imaging systems with complex and expensive
      phased arrays is high, this expenditure will largely be offset by eliminating
      hospitalization and anesthesia and by reducing complications. In effect, an
      investment in this emerging technology will ultimately redound to the benefit of
      the health care delivery system and, most important, to the patient. The FUS
      system provides a safe, repeatable treatment approach for benign tumors (eg,
      uterine fibroid and breast fibroadenoma) that do not require an aggressive
      approach. MR-guided FUS can also be used for debulking cancerous tissue. It has
      already been tested as a breast cancer treatment; its application for other
      malignancies in the brain, liver, and prostate is under development. MR-guided
      FUS offers an attractive alternative to conventional surgery because it
      incorporates intraoperative MR imaging, which provides far more precise target
      definition than is possible with the surgeon's direct visualization of the
      lesion. MR-guided FUS is undeniably the most promising interventional MR imaging
      method in the field of image-guided therapy today. It is applicable not only in
      the thermal coagulative treatment of tumors but also in several other medical
      situations for which invasive surgery or radiation may not be treatment options.
      The use of FUS for treating vascular malformation or functional disorders of the
      brain is also exciting. It is uniquely applicable for image-guided therapy using
      targeted drug delivery methods and gene therapy. Further advances in this
      technology will no doubt improve energy deposition and reduce treatment times. In
      the near future, FUS will offer a viable alternative to conventional surgery and
      radiation therapy; in the longer-term, it may also enable a host of targeted
      treatment methods aimed at eradicating or arresting heretofore intractable
      diseases such as certain brain malignancies and forms of epilepsy.

PMID- 16084420
TI  - Radiofrequency thermal ablation: the role of MR imaging in guiding and monitoring
      tumor therapy.
AB  - Performing RFA procedures under MR imaging involves two distinct processes:
      interactive guidance of the RF electrode into the targeted tumor and monitoring
      the effect of therapy. The justification for using MR imaging for electrode
      guidance is quite similar to its use to guide biopsy and aspiration procedures,
      where MR imaging offers advantages related to superior soft tissue contrast,
      multiplanar capabilities, and high vascular conspicuity that facilitate safe and
      accurate guidance in selected lesions. The major contribution of MR imaging to
      thermal ablation procedures is its ability to monitor tissue changes associated
      with the heating process instantaneously, an attribute that is not paralleled by
      any other currently available imaging modality. Such ability facilitates a
      controlled approach to ablation by helping to detect inadequately treated tumor
      foci for subsequent interactive repositioning of the RF electrode during therapy.
      As such, MR imaging guidance and monitoring enable treatment of the entire tumor
      on a single-visit basis while avoiding undue overtreatment and preserving often
      critically needed organ function. Although knowledge of interventional MR imaging
      concepts and familiarity with its technology and with the related safety issues
      are indispensable for interventional radiologists attempting thermal ablation
      procedures in the MR imaging environment, understanding the tissue basis of
      necrosis imaging is becoming an essential part of the knowledge base for the
      larger sector of general radiologists who are required to interpret the follow-up
      MR imaging scans of the increasing number of thermal ablation patients.

PMID- 16084421
TI  - MR-guided laser ablation.
AB  - MR-guided LITT is a safe and effective treatment modality that improves survival
      in well-selected patients who have liver metastases. A major advantage of MR
      guided LITT is that it can be easily performed under local anesthesia in an
      outpatient setting with a low complication rate.

PMID- 16084422
TI  - MR-guided percutaneous sclerotherapy of low-flow vascular malformations in the
      head and neck.
AB  - MR-guided sclerotherapy is an excellent approach for the treatment of the
      predominant symptoms of congenital low-flow vascular malformations in the head
      and neck. In the authors' experience, this mode of treatment appears to be safe
      and efficient and allows the quantitative verification of therapeutic success
      during follow-up examinations.

PMID- 16084424
TI  - Redefining the low-risk patient with significant atherosclerotic disease.

PMID- 16084425
TI  - On the bright right side.

PMID- 16084426
TI  - Third Annual Mario S. Verani, MD, Memorial Lecture: The future of clinical
      nuclear cardiology.
AB  - It is a great honor and privilege to present the Third Annual Mario S. Verani,
      MD, Memorial Lecture. Mario Verani (1943-2001) will be remembered foremost for
      his major contributions to the field of nuclear cardiology (Figure 1). For
      instance, he was one of the first investigators to recognize that fixed thallium
      defects were often not just scar but could be reversed by coronary
      revascularization. This led to an extensive revision of accepted traditional
      concepts on the meaning of image patterns. Mario's work on risk stratification by
      myocardial perfusion and function imaging after acute myocardial infarction was
      equally pioneering. He also laid out the basic principles for the safe use of
      adenosine for pharmacologic stress testing. Adenosine is now the preferred
      procedure all over the world in millions of patients. Dr Verani was a founding
      member and past president (1996-1997) of the American Society of Nuclear
      Cardiology (ASNC). The day before he died, he received the ASNC Distinguished
      Service Award. Personally, I will remember Mario as a very dear friend. We spent
      many hours together at meetings and gatherings all over the world. I still miss
      his outgoing personality, his warmth, his humor, and his enthusiasm. Above all, I
      enjoyed his comfortable friendship. That this friendship extended itself
      naturally to our wives, Regina and Marjan, made it all the more special. One of
      the best times we had was during a cardiology meeting in Recife, in the country
      of his birth, Brazil. I was greatly amused and, at the same time, impressed by
      the admiration and respect bestowed on him by his fellow Brazilians. One evening,
      we were going some place in the street on foot. We could not walk down the street
      without Mario being stopped by one or another Brazilian cardiologist who wanted
      to speak and consult with him. He was clearly greatly admired and appreciated in
      his country. I jokingly called him "King of Recife," and the king was holding
      audience. We arrived rather late where we were going... . I will always cherish
      the memories of our times together. I am grateful that I could visit Mario at his
      sickbed on the day before he passed away. He was so fragile and, at the same
      time, so courageous. I felt sad that there was so much that we could have
      discussed that we did not. Life seems sometimes full of missed opportunities... .

PMID- 16084427
TI  - Clinical utility of coronary calcium scoring after nonischemic myocardial
      perfusion imaging.
AB  - BACKGROUND: Coronary artery calcium (CAC) scoring is increasingly being used
      after myocardial perfusion imaging (MPI) to detect preclinical coronary artery
      disease (CAD). However, there are few data to support this approach. METHODS AND
      RESULTS: We reviewed 200 consecutive patients without known CAD who were referred
      for CAC scoring shortly after nonischemic MPI. Of these, 13 (6.5%) had CAC scores
      greater than 400, indicating significant CAD; 22 (11%) had CAC scores of 101 to
      400; 27 had CAC scores of 11 to 100; and the remainder (n = 138) has CAC scores
      of 1 to 10. Traditional risk factors and patient characteristics were not
      significant predictors of CAC scores of 101 or greater. However, age and the
      Framingham risk score were predictors of CAC scores greater than 0. At follow-up,
      significantly more patients with CAC scores of 101 or greater had been given the
      advice to take lipid-lowering medication and aspirin compared with those with CAC
      scores of 0. CONCLUSIONS: Of patients referred for CAC scoring after nonischemic
      MPI, 17.5% were identified as having CAD based on a CAC score greater than 100,
      allowing intervention with aggressive medical therapy. Patients who were
      reclassified were not easily identifiable by traditional risk factors, but
      Framingham risk score did predict the presence of CAC. Clinicians modified
      medical therapy based on the results of CAC scoring.

PMID- 16084428
TI  - Contributions of subdiaphragmatic activity, attenuation, and diaphragmatic motion
      to inferior wall artifact in attenuation-corrected Tc-99m myocardial perfusion
      SPECT.
AB  - BACKGROUND: Subdiaphragmatic activity and diaphragmatic motion both contribute to
      inferior wall artifacts in technetium 99m myocardial perfusion single photon
      emission computed tomography (SPECT). METHODS AND RESULTS: We used an
      anthropomorphic phantom with ventricular wall activity, liver/spleen inserts
      containing variable Tc-99m activity, and variable vertical (diaphragmatic) motion
      amplitude. SPECT and transmission scans were obtained on a GE Optima NX camera.
      Data were processed by use of filtered backprojection or attenuation correction
      (AC). Resulting myocardial activity maps were analyzed with standardized inferior
      anterior and anterior-lateral wall ratios. At a subdiaphragmatic-myocardial
      activity ratio of 0.5:1, inferior wall attenuation predominates, producing a cold
      artifact. AC corrects inferior wall activity to the level of the anterior wall
      irrespective of diaphragmatic motion. At a subdiaphragmatic-myocardial activity
      ratio of 1:1, inferior wall counts vary widely depending on the proximity of
      subdiaphragmatic activity to the ventricle. With increasing diaphragmatic
      amplitude, the overlap of subdiaphragmatic activity and inferior wall worsens,
      leading to a complex mixture of cold and hot artifacts, not corrected by AC.
      CONCLUSIONS: Concentration and proximity of subdiaphragmatic Tc-99m activity
      relative to myocardium comprise a major factor in the nature and severity of
      inferior wall artifacts. If the subdiaphragmatic Tc-99m concentration is
      equivalent to that in the myocardium, complex, potentially uninterpretable hot
      and cold inferior wall artifacts are produced.

PMID- 16084429
TI  - Assessment of myocardial perfusion by dynamic N-13 ammonia PET imaging:
      comparison of 2 tracer kinetic models.
AB  - BACKGROUND: Measurement of myocardial blood flow (MBF) by dynamic nitrogen 13
      ammonia (NH(3)) positron emission tomography (PET) uses tracer kinetic modeling
      to analyze time-activity curves. We compared 2 commonly used models with 2
      compartments (2C) and 3 compartments (3C) for quantification of MBF and coronary
      flow reserve (CFR). METHODS AND RESULTS: Seventy-seven patients underwent NH(3)
      PET at rest and during hyperemia. Time-activity curves for blood pool and
      myocardial segments were obtained from short-axis images of dynamic sequences.
      Model fitting of the 2C and 3C models was performed to estimate regional MBF. MBF
      values calculated by 2C and 3C models were 0.98 +/- 0.31 mL.min(-1).g(-1) and
      1.11 +/- 0.37 mL.min(-1).g(-1), respectively, at rest (P < .0001) and 2.79 +/-
      1.18 mL.min(-1).g(-1) and 2.46 +/- 1.02 mL.min(-1).g(-1), respectively, during
      hyperemia (P < .01), resulting in a CFR of 3.02 +/- 1.31 and 2.39 +/- 1.15 (P <
      .0001), respectively. Significant correlation was observed between the 2 models
      for calculation of resting MBF (r = 0.78), hyperemic MBF (r = 0.68), and CFR (r =
      0.68). CONCLUSION: Measurements of MBF and CFR by 2C and 3C models are
      significantly related. However, quantification of MBF and CFR significantly
      differs between the methods. This difference needs to be considered when normal
      values are established or when measurements obtained with different methods need
      to be compared.

PMID- 16084430
TI  - Accuracy of radionuclide ventriculography assessed by magnetic resonance imaging
      in patients with abnormal left ventricles.
AB  - BACKGROUND: We compared gated blood pool single photon emission computed
      tomography (SPECT) (GBPS), planar gated blood pool imaging (planar GBP), and
      cardiac magnetic resonance (CMR) measurements of left ventricular (LV) end
      diastolic volume (EDV) and ejection fraction (EF) in patients with abnormal left
      ventricles. METHODS AND RESULTS: LV functional parameters were measured for 40
      subjects (age, 59 +/- 13 years; 85% male) by GBPS, planar GBP, and CMR. GBPS data
      were analyzed by use of count-threshold software (BP-SPECT) and surface gradient
      software (QBS). Limits of agreement with CMR for EF were -5% to +18%, -15% to
      +14%, and -15% to +16% for BP-SPECT, QBS, and planar GBP, respectively. However,
      limits of agreement with CMR for LV EDV were wide by both GBPS methods: -118 mL
      to +55 mL and -143 mL to +22 mL for BP-SPECT and QBS, respectively. Bland-Altman
      reproducibility limits for EF were -9% to +8%, -6% to +9%, and -7% to +7% by BP
      SPECT, QBS, and planar GBP, respectively, and those for EDV were -46 mL to +48 mL
      and -31 mL to +35 mL by BP-SPECT and QBS, respectively. CONCLUSION: GBPS LV EF
      measurements agree with measurements by CMR and are as reproducible as planar GBP
      measurements. However, wide limits of agreement of radionuclide versus CMR values
      suggest that caution must be applied in interpreting GBPS LV volume results,
      especially for patients with markedly abnormal left ventricles.

PMID- 16084431
TI  - Flattening of the interventricular septum (D-shaped left ventricle) in addition
      to high right ventricular tracer uptake and increased right ventricular volume
      found on gated SPECT studies strongly correlates with right ventricular overload.
AB  - BACKGROUND: Flattening of the interventricular septum (D-shaped left ventricle)
      detected during echocardiographic examination is correlated with significant
      right ventricular (RV) overload. There are no reports of this finding with
      cardiac gated single photon emission computed tomography (SPECT) imaging. We
      report an observational study correlating this finding with the presence of RV
      overload. METHODS AND RESULTS: Retrospectively, we compared 8 cases with
      flattening of the interventricular septum on cardiac gated SPECT imaging for
      which echocardiographic correlations and clinical data were available regarding
      the presence of RV overload. All patients but 1 had pulmonary hypertension
      ranging from 42 to 52 mm Hg measured by echocardiographic Doppler studies. All
      patients but 1 had reasons for RV overload (chronic obstructive pulmonary disease
      in 3, history of atrial septal defect in 3, pulmonary embolism in 1, and
      obstructive sleep apnea in 1). Septal flattening present on gated SPECT images
      was seen in 50% of the cases by echocardiography. Other signs of RV overload (RV
      enlargement, RV hypertrophy) were observed by echocardiography in 5 patients and
      by the gated SPECT in 7 patients. CONCLUSION: The presence of interventricular
      septal flattening on gated SPECT studies correlates with RV overload and should
      be routinely assessed during interpretation of gated SPECT studies.

PMID- 16084432
TI  - Right ventricular pressure-volume loops using simultaneous radionuclide
      angiography with a multiwire gamma camera and right heart catheterization.
AB  - BACKGROUND: The purpose of this study was to generate right ventricular (RV)
      pressure-volume loops (PVLs) from time-activity curves obtained by first-pass
      radionuclide angiography (RNA) and RV pressures obtained by right heart
      catheterization. METHODS AND RESULTS: Short-lived tantalum 178 was used to obtain
      first-pass RNA at baseline (n = 31), after nitroglycerin (n = 5), or after the
      conclusion of cardiac catheterization (n = 13). From the radionuclide-derived RV
      ejection fraction and thermodilution stroke volume, the RV end-diastolic volume
      and end-systolic volume were measured. Special proprietary software was developed
      and used to integrate the pressure and the RNA data. The mean heart rate was 80
      +/- 17 beats/min; RV ejection fraction, 39% +/- 12%; RV end-diastolic volume, 217
      +/- 79 mL; RV end-systolic volume, 142 +/- 74 mL; and RV end-diastolic pressure,
      10 +/- 7 mm Hg. The RV PVLs were of high quality and reproducible. CONCLUSIONS:
      This study provides proof of concept of the feasibility of generating RV PVL; the
      short half-life (10 minutes) and low energy (59 keV) of Ta-178 allow the
      generation of multiple loops at low radiation exposure. Such studies could be
      performed at the bedside and provide a wealth of information that may have
      clinical and research merits.

PMID- 16084433
TI  - A unique method by which to quantitate synchrony with equilibrium radionuclide
      angiography.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms and the
      survival rate in patients with advanced heart failure by improving synchrony.
      However, CRT is not always successful, is costly, and is applied without
      individualization. There is no specific measure of synchrony. The goal of this
      study was to analyze new quantitative parameters of synchrony and compare them
      with established measures. METHODS AND RESULTS: Equilibrium radionuclide
      angiography, phase angle (O), and amplitude quantitate regional contraction
      timing and magnitude and are the basis for new synchrony (S) and entropy (E)
      parameters. S is the vector sum of all amplitudes based on the angular
      distribution of O divided by the scalar sum of the length of all vectors.
      Complete S equals 1, and its absence equals 0. E measures the disorder in the
      region of interest, is 1 with random contraction and 0 with full synchrony, and
      differentiates among differing contraction patterns. Left ventricular S and E
      were measured in 22 normal equilibrium radionuclide angiography studies, where
      regions of interest were drawn from the left ventricle, left atrium, and
      background to analyze model ventricles with normal wall motion (N), ventricles
      with aneurysm (An), ventricles with severe diffuse dysfunction (Diff), and
      ventricles with severe regional dysfunction (Reg). The new S and E parameters
      were highly reproducible and well differentiated among N, An, Diff, and Reg,
      which were not separated by SD O (SD of ventricular phase), which has gained
      popularity as a measure of synchrony. CONCLUSION: Unique scintigraphic parameters
      for the evaluation of ventricular synchrony were derived, and their added value
      was determine compared with established measures. Indications for pacemaker
      therapy now include the treatment of severe congestive heart failure (CHF).
      Atrial triggered biventricular pacemakers reduce CHF symptoms and prolong life in
      patients with cardiomyopathy, severe CHF, left ventricular (LV) ejection fraction
      (EF) lower than 35%, and QRS greater than 120 milliseconds. Such pacing, or
      cardiac resynchronization therapy (CRT), seeks to reduce the heterogeneity and
      increase the synchrony of ventricular activation, conduction, and contraction.
      CRT has improved hemodynamics, increased exercise tolerance, reduced symptoms and
      the need for hospitalization, reversed ventricular remodeling, and reduced the
      all-cause mortality rate in CHF. However, CRT is costly, fails to improve
      symptoms or activity level in more than 30% of patients, and is applied blindly
      without individualization or consideration of lead placement sight. A variety of
      echocardiographic methods have sought to measure synchrony and its serial changes
      with CRT. A recent study presented evidence of the poor reproducibility of
      several widely applied echocardiographic measurements by which to determine
      ventricular synchrony. Magnetic resonance imaging has excellent resolution of
      regional wall motion and has been applied to assess ventricular synchrony and its
      response to pacing therapy. However, these methods are complex and are not well
      established or widely available, and magnetic resonance imaging has not been
      widely applied after pacing. An accurate and reproducible method is needed by
      which to objectively measure regional ventricular synchrony. Phase image
      analysis, a functional method based on the first Fourier harmonic fit of the
      gated blood pool time versus radioactivity curve, generates the parameters of
      amplitude (A), which parallels the extent of regional ventricular contraction or
      stroke volume, and phase angle (O), which represents the timing of regional
      contraction. It was applied early with demonstrated reproducibility to show the
      linkage between electrical and mechanical dyssynchrony and to characterize the
      contraction pattern in heart failure and its alteration with CRT. The SD of
      ventricular O, applied as a marker of synchrony, has been shown to demonstrate
      the beneficial effects of biventricular pacing, and its strong prognostic value
      has been shown in patients with congestive cardiomyopathy and CHF, superior to
      LVEF. The SD O may not be optimal for synchrony evaluation. We sought improved,
      more sensitive parameters to better differentiate synchrony among the spectrum of
      possible patterns of dyssynergy. We derived, initially evaluated, and here
      present new synchrony (S) and entropy (E) parameters, based on the phase method,
      to quantitate regional and global ventricular synchrony and applied them in
      simulation and clinical protocols.

PMID- 16084434
TI  - Assessment of myocardial viability using F-18 fluorodeoxyglucose/Tc-99m sestamibi
      dual-isotope simultaneous acquisition SPECT: comparison with Tl-201 stress
      reinjection SPECT.
AB  - BACKGROUND: This study compared technetium 99m sestamibi/fluorine 18
      fluorodeoxyglucose dual-isotope simultaneous acquisition (DISA) with stress
      reinjection thallium 201 single photon emission computed tomography (SPECT) with
      regard to their ability to detect myocardial viability. METHODS AND RESULTS: The
      study cohort consisted of 42 angiographically significant coronary artery disease
      patients with symptomatic congestive heart failure or regional wall motion
      abnormalities. In total, 398 dysfunctional segments in 40 patients were analyzed
      (2 patients were excluded because of poor-quality F-18 fluorodeoxyglucose
      images). Of the segments, 217 were diagnosed as viable and 144 as nonviable by
      both DISA and Tl-201, 33 were viable by DISA but nonviable by Tl-201, and 4 were
      viable by Tl-201 but nonviable by DISA. Most discrepancies were in the inferior
      wall. Of the 40 patients, 16 underwent revascularization. From the follow-up
      results for the 105 dysfunctional segments in these 16 patients, DISA viability
      appears to be a significant predicting factor (P = .014) for functional recovery
      after revascularization statistically whereas Tl-201 viability does not (P =
      .09). CONCLUSION: Our study suggests that DISA viability provides more accurate
      prediction of postrevascularization functional recovery than Tl-201 viability.
      Given the small number of patients who underwent revascularization, the
      superiority of DISA over Tl-201 in detecting myocardial viability may be firmly
      established by further study on a large scale for patients with profound left
      ventricular dysfunction.

PMID- 16084435
TI  - Intravascular optical coherence tomography: cellular imaging.
AB  - The vast majority of acute coronary events are attributed to rupture or erosion
      of high-risk or vulnerable plaques. Novel imaging techniques are being actively
      sought that can detect quiescent vulnerable features within coronary plaque and
      thereby identify populations at risk, monitor plaque progression, and target
      therapy appropriately. Optical coherence tomography is an intravascular imaging
      modality capable of detecting and characterizing coronary plaque in vivo.
      Recently, optical coherence tomography quantification of macrophage infiltration
      within atherosclerotic plaque ex vivo was demonstrated. Application of this
      technique to clinical practice yields a hybrid image incorporating plaque
      morphology with a measure of biologic activity. In a recently conducted clinical
      study assessing macrophage distributions in patients, evidence supporting both
      the vulnerable plaque model and the hypothesis of multifocal inflammatory risk,
      linked by the common thread of increased macrophage infiltration, has been found.
      These results suggest that elevated multifocal coronary macrophage content,
      present both in culprit lesions and at remote sites, serves as a background for
      heightened risk. Superimposed on this inflammatory background, local increases in
      macrophage content, particularly at the cap surface and at areas at high risk for
      rupture, further promote the instability of individual lesions.

PMID- 16084436
TI  - The clinical importance of electrocardiographic changes during pharmacologic
      stress testing with radionuclide myocardial perfusion imaging.

PMID- 16084437
TI  - Pathologic extracardiac uptake of Tc-99m tetrofosmin identified in the chest
      during myocardial perfusion imaging.

PMID- 16084438
TI  - Massive left pleural effusion resulting in false-positive myocardial perfusion.

PMID- 16084441
TI  - Endovascular procedures for carotid artery occlusive disease.

PMID- 16084442
TI  - Establishing an endovascular carotid stent program.
AB  - FDA approval of carotid stent and distal protection devices has transformed
      carotid artery stenting (CAS) from an investigational procedure to a practical
      application. Recent approval by the Center for Medicare Services (CMS) has
      ensured that CAS will be a part of everyday practice throughout the country. To
      establish a competitive endovascular carotid stent program, one needs to develop
      an effective strategy. The key to success is substance and service. A high
      quality clinical program with excellent communication between the patient and
      referring physician is essential. You must first get access to the patient by
      establishing a clinical practice. As a radiologist, you have the advantage of
      gaining access by identifying appropriate patients through noninvasive vascular
      labs, CTA, and MRA. An algorithm-driven evaluation and treatment protocol with
      good pre- and postoperative care, along with a quality assurance program, will
      ensure that your carotid stent program has substance and delivers optimal
      service. With good planning, you will have a firm clinical foundation for
      treatment of carotid artery stenosis in your community. Putting all of the
      ingredients together will ensure a successful carotid endovascular program.

PMID- 16084443
TI  - Embolic protection devices: methods, techniques, and data.
AB  - Emboli prevention devices have become an integral part of carotid stenting and
      have dramatically lowered the risk of stroke during the procedure. A variety of
      devices are available with different performance characteristics. Filter devices
      are the current mainstay and have high technical success rates. Slow flow through
      the filters can happen with large embolic burdens and should be treated with
      aspiration prior to filter retrieval.

PMID- 16084444
TI  - CaRESS: carotid revascularization using endarterectomy or stenting systems.
AB  - The primary objective of the CaRESS Phase I trial is to determine the sample size
      needed to reliably test the hypothesis that carotid stenting systems with distal
      embolic protection (CAS) is equivalent to carotid endarterectomy (CEA) in the
      treatment of symptomatic and asymptomatic carotid artery disease in a broad-risk
      population. A total of 397 patients were treated at 14 clinical centers. The
      primary endpoint results of combined all-cause mortality and stroke at 30-days
      and 1-year are presented. The CaRESS Phase I study was able to closely resemble
      clinical practice and results suggest equivalence between treatment groups.

PMID- 16084445
TI  - Stroke prevention: carotid intervention based on catheter angiography versus
      noninvasive vascular imaging.
AB  - Historically, imaging evaluation before carotid revascularization by
      endarterectomy or stenting has relied on targeting the cervical carotid using
      catheter angiography as the gold standard. This approach underestimates the
      anatomic and functional importance of the brain as the target organ by focusing
      the decision-making process on an isolated segment of the circulation. Since
      revascularization alternatives have been expanded to include the more proximal
      aortic and more distal intracranial circulations, it is essential to image the
      vascular tree from the heart to the brain. Equally important is accurate clinical
      correlation and functional imaging correlation, so that unnecessary surgery is
      avoided and there is no lost opportunity for stroke prevention.

PMID- 16084446
TI  - Advances in stent-assisted management of intracranial occlusive disease and
      cerebral aneurysms.
AB  - The use of stents in the intracranial circulation has been made possible by rapid
      developments in stent technology in recent years. Considerable improvements in
      stent design, delivery devices, and technique have expanded the use of stenting
      to the treatment of intracranial disorders. This article reviews the indications
      for endovascular stenting for cerebral aneurysms and intracranial atherosclerosis
      and describes the peri-procedure management and technique applied at the
      Department of Neurosurgery at the University at Buffalo.

PMID- 16084447
TI  - Training, competency, and credentialing standards for carotid stenting.
AB  - Appropriate and adequate training is the hallmark of modern medical care. The
      foundation of medical education in the United States is accredited medical
      schools combined with formal residencies and fellowship training programs. This
      concept has been officially recognized by the Accreditation Council of Graduate
      Medical Education, the Federal Licensing Examination, all state medical boards,
      the federal government, and all medical professions and societies. Appropriate
      medical education is of utmost importance for procedures and therapies that offer
      the greatest risk to patients. There is little doubt that any procedure that has
      "stroke" as a defined potential risk would qualify as one that should require
      formal, adequate, and officially provided education. Hospitals and accrediting
      authorities such as the Joint Commission on Accreditation of Healthcare
      Organizations are obligated to ensure adequate standards of patient care in the
      United States.

PMID- 16084448
TI  - The supraaortic and vertebral endovascular interventions.

PMID- 16084449
TI  - Cyclin D1 expression in melanocytic lesions of the skin.
AB  - BACKGROUND: Progression through the cell cycle is controlled by cyclins, cyclin
      dependent kinases, and cyclin-dependent kinase inhibitory proteins. The role of
      cyclin D1 in the development and progression of melanomas is controversial. The
      goal of this study is to evaluate the role of cyclin D1 in benign and malignant
      melanocytic lesions of the skin. METHODS: A total of 126 pigmented lesions of the
      skin including compound nevi (21), intradermal nevi (18), melanoma in situ (28),
      primary invasive melanomas (30), and metastatic melanoma (29) were evaluated for
      cyclin D1 expression. The following tiered system was used for scoring: 0%
      nuclear staining (score 0), 1% to 19% nuclear staining (score 1), 20% to 49%
      nuclear staining (score 2), and 50% or greater nuclear staining (score 3).
      RESULTS: Average scores were significantly higher for primary melanomas compared
      with nevi and for in situ melanomas compared with primary invasive melanomas. The
      average score for metastatic melanomas was not significantly different compared
      with primary invasive melanomas. Scores for primary invasive melanomas did not
      correlate with depth of invasion or presence of metastases. Compound nevi
      exhibited a slightly higher level of cyclin D1 expression compared with
      intradermal nevi. CONCLUSION: Although primary melanomas show a higher level of
      cyclin D1 expression compared with nevi, cyclin D1 appears to have little role in
      development of a metastatic phenotype. It is not clear why lesions localized near
      the dermal-epidermal junction express higher levels of cyclin D1. Further studies
      are indicated to ascertain the biologic role and practical utility of cyclin D1
      in melanocytic lesions of the skin.

PMID- 16084450
TI  - Thyroid transcription factor-1 expression in thyroid-like nasopharyngeal
      papillary adenocarcinoma: report of 2 cases.
AB  - We present the cases of 2 pediatric patients with low-grade nasopharyngeal
      papillary adenocarcinoma with features suggestive of thyroid origin. Both cases
      showed strong nuclear immunoreactivity for thyroid transcription factor-1 protein
      and positive immunostaining for cytokeratins 7 and 19. After thyroid imaging
      studies, local excision was performed in both patients. The patients remain free
      of disease 2 and 15 years after treatment, with no evidence of lesions in the
      thyroid or elsewhere.

PMID- 16084451
TI  - Bizarre stromal cells in ischemic bowel disease.
AB  - The presence of bizarre stromal cells has been reported in gastrointestinal and
      extraintestinal lesions. We describe, for the first time, the presence of bizarre
      stromal cells with a cytomegalovirus (CMV)-like appearance or ganglion-like cells
      in 3 cases of ischemic colitis. The 3 patients were males ranging in age from 62
      to 78 years, showed varying degrees of cardiovascular insufficiency, and were
      diagnosed with ischemic colitis. Colonic biopsies showed changes of ischemic
      colitis of variable severity. Common to all 3 cases, within the granulation
      tissue, stromal cells showed a broad spectrum of morphologic alterations, ranging
      from just nuclear enlargement to striking atypical features, large pleomorphic,
      hyperchromic nuclei, and eccentric prominent nucleoli. Occasionally, these cells
      displayed an eosinophilic oval nuclear inclusion, surrounded by a clear halo,
      resembling CMV inclusions. In conclusion, the etiopathogenesis of these cells can
      be partially explained by hypoxia, inflammation, regeneration/repair, and cell
      turnover alone or, more probably, in combination in the granulation tissue
      response to injury. The morphologic spectrum of bizarre stromal cells and
      ganglion-like cells suggests an obvious differential diagnosis, which includes
      carcinoma and sarcoma. The finding of enlarged cells with eccentric intranuclear
      eosinophilic inclusions requires the exclusion of CMV. However,
      immunohistochemistry, together with an awareness of those atypical stromal cells,
      can occur in the setting of ulceration and/or polypoid lesions, preventing an
      incorrect diagnosis.

PMID- 16084452
TI  - Low-grade malignant perineurioma (perineurial sarcoma) of soft tissue: a
      potential diagnostic pitfall on fine needle aspiration.
AB  - A case of low-grade malignant perineurioma presenting as a mass in the thigh is
      described. The patient was a 76-year-old woman with an enlarging painful mass on
      her right lateral thigh over the past 2 months. Thorough clinical and
      radiological studies did not reveal any evidence of tumor elsewhere. The patient
      underwent fine needle aspiration of the mass, which revealed pleomorphic spindle
      cells in small clusters or dispersed as single cells within myxoid stroma,
      cytologically consistent with a high-grade sarcoma. At surgery, the tumor was
      found to be entirely confined within the muscle. Grossly, the tumor measured 6.5
      cm in greatest diameter and showed a gray-white fleshy cut surface that was well
      circumscribed but unencapsulated. Histologic examination showed a highly cellular
      spindle cell proliferation embedded within myxoid stroma. The tumor cells showed
      mild to moderate nuclear pleomorphism with minimal mitotic activity. No evidence
      of hemorrhage or necrosis was noted. The tumor irregularly invaded the
      surrounding skeletal muscle. Immunohistochemical studies showed weak membranous
      positivity for epithelial membrane antigen and focal cytoplasmic positivity for
      CD34; stains for smooth muscle actin, cytokeratin AE1/AE3, desmin, CD56, H
      caldesmon, calponin, and S-100 protein were negative. Electron microscopy showed
      cells with thin, elongated cytoplasmic processes extending along connective
      tissue in a parallel, onion-like arrangement and prominent subplasmalemmal
      pinocytotic activity. The marked pleomorphism displayed on fine needle aspiration
      observed in this case can lead to a mistaken diagnosis of high-grade sarcoma
      resulting in unnecessarily aggressive management.

PMID- 16084453
TI  - The hysterectomy.

PMID- 16084454
TI  - Pulmonary artery angiosarcoma: a clinicopathologic and radiological correlation.
AB  - A 69-year-old man presented with cough, shortness of breath, and fatigue. He was
      initially treated for allergies and then for pulmonary embolism. Radiologically,
      a tumor mass was found to occlude the right pulmonary artery and involve the
      pulmonary trunk. A right pneumonectomy was performed. Histologically, a cellular
      malignant spindle and epithelioid tumor with areas of necrosis and brisk mitotic
      activity was seen. In some areas, the tumor appeared to form vascular channels.
      Focal osteosarcomatous differentiation was present. Immunohistochemical studies
      were performed including vimentin, smooth muscle actin, desmin, CD31, CD34, S100,
      and pan-cytokeratin. The tumor cells were positive for CD31 and vimentin and
      negative for pan-cytokeratin, CD34, and S100. Two months after surgery, the
      patient was alive and well.

PMID- 16084455
TI  - Mediastinal myxopapillary ependymoma primary or late metastases of paracoccygeal
      ependymoma: a case report.
AB  - A 25-year-old woman presented in 2002 with progressive shortness of breath and
      weight loss. A computed tomographic scan of the chest showed a huge anterior
      mediastinal mass, and pathological examination of a mediastinoscopic needle
      biopsy revealed typical myxopapillary ependymoma, an extremely unusual diagnosis
      at this site. Further workup and questioning of the patient revealed that she had
      opted not to disclose a history of surgery for right gluteal fold mass in 1993,
      which was primarily treated with surgery followed by radiotherapy for relapse.
      Review of the histology of the excised mass showed a myxopapillary ependymoma,
      similar to current histology. Clinical examination of the local gluteal and
      paracoccygeal site, computed tomographic imaging, and magnetic resonance imaging
      failed to demonstrate any evidence of recurrent disease in soft tissue or bone.
      The case is presented, and this very unusual presentation is discussed.

PMID- 16084456
TI  - Metaplastic synovial cyst in male breast.
AB  - Metaplastic synovial cyst (synovial metaplasia of the skin) refers to a cyst
      lined by a membrane resembling hyperplastic synovial villi. Synovial-like
      metaplasia has been described around prostheses and breast implant capsules and
      may occur in postsurgical cutaneous scars, unrelated to prostheses or implants.
      We describe a metaplastic synovial cyst occurring in the left breast of a 23-year
      old man 2 years after surgical treatment of gynecomastia. The expanding
      clinicopathologic scenario of metaplastic synovial cyst, in scar tissue in male
      breast unrelated to mammary implants, and as a potential complication after
      surgical treatment of gynecomastia is highlighted.

PMID- 16084457
TI  - Pulmonary large cell carcinoma with rhabdoid phenotype.
AB  - Large cell carcinoma of the lung with a rhabdoid phenotype is very rare. We
      present a 55-year-old man with multiple nodules in his lung. He had an emergency
      operation because of abundant hemoptysis. The microscopic appearance was a large
      cell carcinoma with a pure rhabdoid phenotype. There were no foci of any other
      carcinomatous components. Tumor cells had abundant eosinophilic cytoplasmic
      globules and eccentric nuclei and did not adhere to each other. Histochemically,
      these cells were periodic acid-Schiff-negative. Immunohistochemically, vimentin
      and neuron-specific enolase were positive. Epithelial membrane antigen was
      focally and weakly positive, p53 was positive in 60% of tumoral cells, and Ki-67
      (MIB-1 labeling index) was 50%. The patient died of disseminated disease 2 months
      after the operation.

PMID- 16084458
TI  - Lung infection due to opportunistic fungus, Phialemonium obovatum, in a bone
      marrow transplant recipient: an emerging infection with fungemia and Crohn
      disease-like involvement of the gastrointestinal tract.
AB  - We report the first case of Phialemonium obovatum fungemia with subsequent
      caseating granulomatas in the lung and Crohn disease-like involvement of the
      gastrointestinal tract in a bone marrow transplant recipient. This phaeoid fungus
      has been rarely described as an opportunistic infection in immunosuppressed
      patients. The patient was diagnosed with chronic myelogenous leukemia and
      underwent subsequent peripheral bone marrow transplant. After 6 months, he
      developed graft-versus-host disease of the skin and liver with fever and severe
      diarrhea. Fecal bacterial cultures and cytomegalovirus serologies were negative.
      Computed tomographic scan showed a peripheral pulmonary mass. A lung wedge biopsy
      of the lesion showed septate branching hyphae (4-5 microm in diameter) with
      terminal globular structures (10 microm in diameter). The hyphae were similar in
      width to that of an Aspergillus species but had a more moniliform appearance.
      Blood cultures grew a pure culture of P. obovatum. He was treated with
      amphotericin B and itraconazole for 6 months without remission of the diarrhea.
      Biopsies of the stomach, colon, and rectum showed granulomatous inflammation with
      marked crypt distortion simulating Crohn disease. In retrospect, the fungus was
      found to be resistant to both of the aforementioned drugs and susceptible to
      voriconazole and posaconazole. The gastrointestinal findings raise the
      possibility of further dissemination of a partially treated Phialemonium
      infection.

PMID- 16084459
TI  - Cholesterol crystal embolization diagnosed on bladder transurethral resection.
AB  - Cholesterol crystal embolization (CCE) is a severe systemic disorder caused by
      vascular migration of cholesterol crystals originating from ulcerative
      atherosclerotic plaques located in large arteries. We report 2 cases of CCE
      diagnosed on bladder transurethral resection in 2 men aged 94 and 72 years. Both
      patients had atherosclerosis disease. One patient had been treated by heparin 1
      month before for pulmonary embolism and the other had had a coronary angiography
      and bypass graft surgery 5 months before for silent myocardial infarction. One
      patient presented with hematuria and the other with acute renal failure.
      Cystoscopy showed multiple papillary tumors of the bladder wall. Bladder
      transurethral resections showed transitional cell carcinoma with cholesterol
      crystals occluding the lumen of small arterioles in the submucosa. Eight cases of
      CCE in the bladder wall have been reported in the literature in 3 women and 5 men
      aged 56 to 79 years. Cholesterol crystal embolization is often discovered in the
      bladder wall on necropsy specimens. Only 2 cases have been fortuitously
      discovered on bladder transurethral resection performed for transitional cell
      carcinoma. Cholesterol crystal embolization in the bladder wall is often a marker
      of severe disease although the evolution is quite favorable in our patients,
      still alive 1 and 2 years after diagnosis.

PMID- 16084460
TI  - Pancreatic endocrine tumor coexistent with serous microcystic adenoma: report of
      a case and review of the literature.
AB  - Serous cystadenomas of the pancreas have been classified as benign exocrine
      tumors. There have been rare cases of malignant behavior, and in exceptional
      cases, coexisting neoplasms have been reported. We report a case of a coexistent
      neuroendocrine tumor identified within a serous cystadenoma in a 78-year-old
      woman, which was discovered incidentally after complete resection of the tumor.
      Given the unpredictable metastatic potential of neuroendocrine tumors of the
      pancreas, we advocate complete resection of all pancreatic cystic tumors,
      combined with careful sampling of the pathological specimen to rule out a
      coexistent potentially malignant neoplasm.

PMID- 16084461
TI  - Advances in the pathological diagnosis and biology of acute lymphoblastic
      leukemia.
AB  - An accurate diagnosis of acute lymphocytic leukemia requires careful examination
      of the morphology, immunophenotype, genetic features, clinical characteristics,
      and molecular findings. This multiparametric approach should be used to achieve
      optimal evaluation of every suspected case of acute lymphocytic leukemia.

PMID- 16084462
TI  - Teaching behavioral pain management to healthcare professionals: a systematic
      review of research in training programs.
AB  - Pain is a common and potentially debilitating condition. Whereas there is vast
      literature on developmentally appropriate behavioral techniques for pain
      management, results of curriculum evaluations and knowledge surveys reveal a
      dearth of awareness of these strategies in healthcare professionals. As a result,
      the development and evaluation of pain management training programs are important
      endeavors. Results of studies evaluating such programs are promising and suggest
      that training might be an effective means of impacting healthcare professionals'
      knowledge, attitudes, and even patient care. These results must be interpreted
      with caution, however, because the literature contains several conceptual and
      methodologic limitations. These limitations, in combination with the wide
      diversity in program components, format of delivery, and research methods,
      preclude definitive conclusions on the most practical and effective means to
      provide training. To address this question, further systematic work on the
      development and evaluation of pain management training programs is warranted.
      PERSPECTIVE: To address the problems of dissemination of behavioral pain
      management techniques, the development and evaluation of pain management training
      programs are important endeavors. The current article presents a systematic
      review of studies evaluating such programs and provides recommendations for
      future systematic work in this area.

PMID- 16084463
TI  - Intrarectal lidocaine is an effective treatment for abdominal pain associated
      with diarrhea-predominant irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is one of the most common disorders seen by
      gastroenterologists. Visceral hypersensitivity is now well recognized as a
      clinical marker for the disease. Intrarectal lidocaine has been previously shown
      to decrease pain report from rectal distension in patients with IBS without any
      significant serum lidocaine levels. We conducted a prospective, double-blind,
      crossover trial on 10 patients with IBS to evaluate the effects of 300 mg
      intrarectal lidocaine jelly on abdominal pain. Ten Caucasian premenopausal women
      who met the Rome II criteria for diarrhea-predominant IBS were recruited into the
      study. All of the patients that participated had intermittent left lower quadrant
      pain and diarrhea. Each patient participated in 2 sessions in which saline jelly
      (placebo) and lidocaine jelly was administered on a double-blind, crossover
      basis. Patients participated in these sessions at a time when their ongoing pain
      was at least 3 on a 0 to 10 visual analogue scale. In comparison to placebo
      saline jelly, lidocaine jelly significantly decreased abdominal pain (P < .02)
      for at least 4 hours. None of the patients experienced any side effects.
      Intrarectal lidocaine may be a potentially useful treatment for chronic abdominal
      pain in IBS. PERSPECTIVE: The possible presence of abnormal sodium channels in
      the rectal and or colonic visceral afferents of patients with IBS might serve as
      a clue as to the effectiveness of rectal lidocaine. The dose of lidocaine used in
      this study may be of sufficient strength to normalize aberrant sodium channels
      that may be present in the colon of patients with IBS without affecting normal
      sodium channels of either IBS or control subjects.

PMID- 16084464
TI  - Hypervigilance and attentional fixedness in chronic musculoskeletal pain:
      consistency of findings across modified stroop and dot-probe tasks.
AB  - Results from modified Stroop and dot-probe tasks have provided mixed evidence
      regarding attentional biases for sensory and affect pain stimuli in chronic pain
      patients. No studies have compared the same groups of chronic pain and healthy
      control participants on both tasks. We tested 36 patients with chronic
      musculoskeletal pain and 29 healthy control subjects on the modified Stroop and
      dot-probe tasks. Stimuli comprised affect pain, sensory pain, physical
      catastrophe, and neutral words. There was no evidence to suggest differential
      processing of threat cues by patients and control subjects on the modified Stroop
      task. All participants did, however, show differential processing of affect pain
      words. This was evident on both masked and unmasked presentation formats. There
      were no significant interactions between clinical status and threat word type
      observed for any of the indices of selective attention derived from the dot-probe
      task, but all participants had difficulty disengaging attention from affective
      pain and health catastrophe words. Findings were not influenced by individual
      differences in mood, anxiety, or fear of pain. Correlational analyses of the
      standard (unmasked) Stroop interference index and dot-probe indices of selective
      attention revealed a consistent lack of significant association, suggesting that
      the 2 tasks might be measuring different phenomena. Taken together, these
      findings provide evidence that chronic pain patients and healthy control
      participants do not differ in the way they attend to threatening linguistic
      stimuli. PERSPECTIVE: Some patients with chronic pain might have trouble paying
      attention to anything other than the affective components of pain and associated
      catastrophic health consequences. Interventions that specifically target this
      attentional fixedness might facilitate shifting attention to other targets and
      thereby reduce pain-specific anxiety and fear.

PMID- 16084465
TI  - Bilateral chronic constriction of the sciatic nerve: a model of long-term cold
      hyperalgesia.
AB  - Effects of chronic constriction injury (CCI) and sham surgery of both sciatic
      nerves were evaluated for reflex lick/guard (L/G) and operant escape responses to
      thermal stimulation of rats. Experiment 1 compared L/G and escape responses to
      0.3 degrees C, 43 degrees C, and 47 degrees C stimulation during a period of 60
      days after CCI. Experiment 2 evaluated escape from 44 degrees C, 47 degrees C,
      and 10 degrees C for 100 days after CCI. The rats escaped from heat or cold
      stimulation of the paws in a dark compartment by climbing on a thermally neutral
      platform in a brightly lit compartment. For reflex testing, a single compartment
      provided no escape option. There was no significant effect of bilateral CCI on
      reflex or escape responses to nociceptive heat. However, there were long-term
      increases in the duration of L/G responding during trials of 0.3 degrees C
      stimulation and in the duration of escape responding to 10 degrees C.
      Hyperalgesia for cold was confirmed by a preference test, with a 2-compartment
      shuttle box with one floor heated (45 degrees C) and the other floor cooled (10
      degrees C). Occupancy of the heated compartment was significantly increased by
      CCI (indicating a relative aversion for cold). PERSPECTIVE: For preclinical
      testing of treatments for allodynia/hyperalgesia after nerve injury, it is
      crucial to use methods of testing that are sensitive to effects on nociception
      throughout the neuraxis. Operant escape testing satisfies this criterion and is
      sensitive to bilateral CCI of rats, which avoids asymmetric postural/motor
      influences of unilateral CCI.

PMID- 16084466
TI  - Factors associated with marital satisfaction and mood among spouses of persons
      with chronic back pain.
AB  - Few studies have examined the impact of chronic pain on the spouse. In this study
      the impact of pain and disability as rated by both the patient and the spouse on
      spouse marital satisfaction and affective distress was examined in 110 couples.
      Zero-order correlations indicated that absolute ratings of perceived disability
      by the spouse, rather than discrepancies between spouse and patient ratings, were
      most highly associated with spouse marital dissatisfaction and affective
      distress. Predictors of spouse marital satisfaction and distress were examined by
      using simultaneous multiple regression. Spouse ratings of greater physical
      disability were significantly related to greater spouse affective distress.
      Spouse ratings of higher psychosocial disability, lower spouse marital
      satisfaction, and being a patient of male gender were marginally related to
      higher spouse affective distress. Spouse marital dissatisfaction was
      significantly associated with patient ratings of greater psychosocial disability
      and lower pain. Spouse-rated psychosocial disability and affective distress were
      also marginally related to spouse marital satisfaction. These findings highlight
      the importance of patient disability, particularly limitations in function as
      perceived by the spouse, on spouse adjustment. PERSPECTIVE: The impact of chronic
      pain on the spouse of the person with pain has received little empirical
      attention. The present study examines the relationship between patient and pain
      related factors and psychosocial adjustment in the spouse.

PMID- 16084467
TI  - Development and validation of the Asian version of the oucher: a pain intensity
      scale for children.
AB  - The present study was designed to develop and test the validity of the Asian
      version of the Oucher pain intensity scale, with color photographs of Taiwanese
      children as the pain intensity cues. A series of 3 studies were conducted. The
      aim of the first study was to create male and female versions of the Asian Oucher
      poster. Each poster consisted of 6 color photographs of children's faces, ranging
      from "no hurt at all" (scored as 0) to the "biggest hurt you could ever have"
      (scored as 5). In the second study, 220 children aged 3 to 6 years were recruited
      to examine the content validity. Children who were able to complete a Piagetian
      seriation task were asked to choose the sequence of 6 photographs. Photo
      sequences were adjusted according to the study findings. The third study was
      conducted to examine the convergent, discriminate, and clinical validity for
      children who are at different levels of pain intensity. In total, 111 children
      aged 3 to 10 years old who were experiencing surgical pain were recruited. The
      construct validity of the Asian Oucher was supported. PERSPECTIVE: This study
      developed an Asian version of Oucher, with photographs of facial expressions of
      real Taiwanese children who were experiencing pain. The Asian Oucher can assess
      pain for children as young as 3 years old.

PMID- 16084469
TI  - Motor unit synchronization is reduced in anterior knee pain.
AB  - Anterior knee pain (AKP) is common and has been argued to be related to poor
      patellofemoral joint control due to impaired coordination of the vasti muscles.
      However, there are conflicting data. Changes in motor unit firing may provide
      more definitive evidence. Synchronization of motor unit action potentials (MUAPs)
      in vastus medialis obliquus (VMO) and vastus lateralis (VL) may contribute to
      coordination in patellofemoral joint control. We hypothesized that
      synchronization may be reduced in AKP. Recordings of single MUAPs were made from
      VMO and multiunit electromyograph (EMG) recordings were made from VL. Averages of
      VL EMG recordings were triggered from the single MUAPs in VMO. Motor units in VL
      firing in association with the VMO motor units would appear as a peak in the VL
      EMG average. Data were compared to previous normative data. The proportion of
      trials in which a peak was identified in the triggered averages of VL EMG was
      reduced in people with AKP (38%) compared to controls (90%). Notably, although
      80% of subjects had values less than controls, 20% were within normal limits.
      These results provide new evidence that motor unit synchronization is modified in
      the presence of pain and provide evidence for motor control dysfunction in AKP.
      PERSPECTIVE: This study shows that coordination of motor units between the medial
      and lateral vasti muscles in people with anterior knee pain is reduced compared
      to people without knee pain. It confirms that motor control dysfunction is a
      factor in this condition and has implications for selection of rehabilitation
      strategies.

PMID- 16084468
TI  - Ethanol withdrawal-associated allodynia and hyperalgesia: age-dependent
      regulation by protein kinase C epsilon and gamma isoenzymes.
AB  - Ethanol (EtOH) withdrawal increases sensitivity to painful stimuli in adult rats.
      In this study, withdrawal from a single, acute administration of EtOH dose
      dependently produced mechanical allodynia and thermal hyperalgesia in postnatal
      day 7 (P7) rats. In contrast, P21 rats exhibited earlier and more prolonged
      mechanical allodynia but not thermal hyperalgesia. For both P7 and P21 rats,
      blood and spinal cord EtOH levels peaked at 30 minutes after administration, with
      P7 rats achieving overall higher spinal cord concentrations. Protein kinase C
      (PKC) has been implicated in mediating pain responses. Inhibitory PKC- and gamma
      specific peptides attenuated mechanical allodynia and thermal hyperalgesia in P7
      rats, whereas only the PKCgamma inhibitor prevented mechanical allodynia in P21
      rats. Immunoreactive PKC in dorsal root ganglion and PKCgamma in lumbar spinal
      cord increased at 6 hours after EtOH administration in P7 rats. In P21 rats, the
      density of PKC immunoreactivity remained unchanged, whereas the density of
      PKCgamma immunoreactivity increased and translocation occurred. These studies
      demonstrate developmental differences in neonatal nociceptive responses after
      withdrawal from acute EtOH and implicate a role for specific PKC isozymes in EtOH
      withdrawal-associated allodynia and hyperalgesia. PERSPECTIVE: This study
      examines age-specific nociceptive responses after ethanol exposure by using 2
      different ages of rats. The results suggest that ethanol age-dependently alters
      sensitivity to mechanical and thermal stimuli via specific protein kinase C
      isozymes. These results begin to ascertain the mechanisms that produce abnormal
      pain after alcohol exposure.

PMID- 16084470
TI  - A framework for modeling health behavior protocols and their linkage to
      behavioral theory.
AB  - With the rise in chronic, behavior-related disease, computerized behavioral
      protocols (CBPs) that help individuals improve behaviors have the potential to
      play an increasing role in the future health of society. To be effective and
      widely used CBPs should be based on accepted behavioral theory. However,
      designing CBPs while at the same time specifying their linkages to behavioral
      theory and developing reusable CBP components (interventions) are challenges to
      developers of CBPs. Having an ontology with which to describe CBPs could help
      with these issues. As a first step towards creating such an ontology, we modeled
      PACE-Adolescent, a theory-based behavioral protocol that uses the Stages of
      Change Model and Social Cognitive Theory, using PROTEGE-2000, an ontology editor
      and knowledge acquisition system. We created a three-part knowledge model. Two
      sub-ontologies described behavioral interventions and psychological theories. The
      third component, implemented using Guideline Interchange Format (GLIF3), provided
      a way to describe the structure of a protocol and to link intervention resources
      and groups of actions to elements of psychological theory. Using this framework,
      we formally described the PACE-Adolescent protocol. Creating knowledge models
      such as this may lead to improvements in the design and evaluation of
      computerized health behavior protocols.

PMID- 16084471
TI  - Individualizing generic decision models using assessments as evidence.
AB  - Complex decision models in expert systems often depend upon a number of utilities
      and subjective probabilities for an individual. Although these values can be
      estimated for entire populations or demographic subgroups, a model should be
      customized to the individual's specific parameter values. This process can be
      onerous and inefficient for practical decisions. We propose an interactive
      approach for incrementally improving our knowledge about a specific individual's
      parameter values, including utilities and probabilities, given a decision model
      and a prior joint probability distribution over the parameter values. We define
      the concept of value of elicitation and use it to determine dynamically the next
      most informative elicitation for a given individual. We evaluated the approach
      using an example model and demonstrate that we can improve the decision quality
      by focusing on those parameter values most material to the decision.

PMID- 16084472
TI  - A framework for capturing the interactions between laypersons' understanding of
      disease, information gathering behaviors, and actions taken during an epidemic.
AB  - This paper provides a description of a methodological framework designed to
      capture the inter-relationships between the lay publics' understanding of health
      related processes, information gathering behaviors, and actions taken during an
      outbreak. We developed and refined our methods during a study involving eight
      participants living in severe acute respiratory syndrome (SARS)-affected areas
      (Hong Kong, Taiwan, and Toronto). The framework is an adaptation of narrative
      analysis, a qualitative method that is used to investigate a phenomenon through
      interpretation of the stories people tell about their experiences. From our work,
      several hypotheses emerged that will contribute to future research. For example,
      our findings showed that many decisions in an epidemic are carefully considered
      and involve use of significant information gathering. Having a good model of lay
      actions based on information received and beliefs held will contribute to the
      development of more effective information support systems in the event of a
      future epidemic.

PMID- 16084475
TI  - He never once doubted.

PMID- 16084474
TI  - Deterministic projection by growing cell structure networks for visualization of
      high-dimensionality datasets.
AB  - Recent advances in clinical proteomics data acquisition have led to the
      generation of datasets of high complexity and dimensionality. We present here a
      visualization method for high-dimensionality datasets that makes use of neuronal
      vectors of a trained growing cell structure (GCS) network for the projection of
      data points onto two dimensions. The use of a GCS network enables the generation
      of the projection matrix deterministically rather than randomly as in random
      projection. Three datasets were used to benchmark the performance and to
      demonstrate the use of this deterministic projection approach in real-life
      scientific applications. Comparisons are made to an existing self-organizing map
      projection method and random projection. The results suggest that deterministic
      projection outperforms existing methods and is suitable for the visualization of
      datasets of very high dimensionality.

PMID- 16084476
TI  - Part 1. Injuries to the brachial plexus: mechanisms of injury and identification
      of risk factors.
AB  - Upper-arm weakness (paresis) or paralysis indicates peripheral-nerve damage to
      the brachial plexus, a network of lower cervical and upper thoracic spinal nerves
      supplying the arm, forearm, and hand. Physical findings reflect muscle paralysis
      from spinal nerve roots. The mechanism of injury includes maternal, obstetric,
      and infant factors that apply traction on or compression to the anatomically
      vulnerable brachial plexus. Nerve regeneration can occur if nerve tissue
      components are preserved. Recovery is affected by multiple factors, including the
      type and site of injury, intervention timing, and developmental factors. The
      majority of injuries recover in days or months; however, residual deficits can
      persist. Part 1 of 2 of this article provides an overview of the neurophysiology
      of peripheral-nerve damage and nerve regeneration. The multifactorial etiology of
      brachial plexus injuries will be reviewed. Photographs and on-line video clips
      will enhance the description of the brachial plexus injury classifications and
      illustrate mechanisms of shoulder dystocia and obstetric relief maneuvers. A
      systematic approach to the physical examination will be explored in Part 2.
      Serial evaluation of motor function recovery is essential and is accomplished by
      appropriate referrals and follow-up. Part 2 will also describe treatment options
      and discuss anticipatory parent guidance.

PMID- 16084473
TI  - Extracting information on pneumonia in infants using natural language processing
      of radiology reports.
AB  - Natural language processing (NLP) is critical for improvement of the healthcare
      process because it can encode clinical data in patient documents. Many clinical
      applications such as decision support require coded data to function
      appropriately. However, in order to be applicable for healthcare, performance
      must be adequate. A valuable automated application is the detection of infectious
      diseases, such as surveillance of pneumonia in newborns (e.g., neonates) because
      the disease produces significant rates of morbidity and mortality, and manual
      surveillance is challenging. Studies have demonstrated that automated
      surveillance using NLP is a useful adjunct to manual surveillance and an
      effective tool for infection control practitioners. This paper presents a study
      evaluating the feasibility of an NLP-based monitoring system to screen for
      healthcare-associated pneumonia in neonates. We estimated sensitivity,
      specificity, and positive predictive value by comparing results with clinicians'
      judgments. Sensitivity was 71% and specificity was 99%. Our results demonstrated
      that the automated method was feasible.

PMID- 16084477
TI  - A case report of the transport of an infant with a tension pneumopericardium.
AB  - Neonatal pneumopericardium is a potentially fatal complication of positive
      pressure ventilation and has become rare with the advent of surfactant
      replacement therapy. The clinical diagnosis, stabilization, treatment, and
      nursing care of an infant with pneumopericardium has not previously been
      discussed in the nursing literature. In this case report, delays in the
      recognition and definitive treatment of the pneumopericardium were encountered,
      resulting in the transport of an infant with a tension pneumopericardium and
      pneumoperitoneum. Root-cause analysis is used to identify contributing factors
      and examine system changes necessary to prevent the transport of another patient
      with a similar potentially life-threatening condition. Pneumopericardium should
      be suspected in any infant with an acute deterioration, especially in the
      presence of normal, equal breath sounds and muffled heart sounds, because prompt
      recognition and definitive treatment may be life-saving.

PMID- 16084478
TI  - The primacy of work and fathering preterm infants: findings from an interpretive
      phenomenological study.
AB  - PURPOSE: To improve our understanding of fathers of preterm infants by examining
      their meanings of work and exploring the impact of their work on their early
      transition to fatherhood. SUBJECTS: The sample included 9 white fathers between
      the ages of 22 and 40 years, who had infants born between 25 and 32 weeks
      gestation. DESIGN AND METHODS: This report explores one theme that emerged from a
      broader interpretive phenomenological study. Fathers were interviewed 6 to 8
      times over a 6-month period, beginning within 1 month of the birth of their
      infant and continuing after neonatal intensive care unit (NICU) discharge.
      Interview guides were used only to initiate conversation; probing, clarifying
      questions helped fathers provide detailed stories of what they did, thought, and
      felt about specific situations. Transcriptions of all 63 interviews were treated
      as meaningful text and analyzed using interpretive methods. PRINCIPAL RESULTS:
      Fathers' narratives revealed the primacy of work in their lives; work remained a
      pivotal focus even after an early birth. Fathers returned to work quickly after
      their infant's birth. They approached their work with a renewed sense of fervor
      in order to provide financially for their families. They found comfort in their
      work because in the work setting they felt that they were the experts, as opposed
      to feeling like novices in the NICU. The most stressful aspect of the experience
      was juggling their time between work and the outside world. CONCLUSIONS: Fathers
      may respond to the experience of having a premature infant very differently from
      mothers. Because fathers' stressors often lie outside the NICU, their stressors
      may be invisible to healthcare providers. A deeper understanding of fathering
      must consider the social, familial, and historical processes that shape fathering
      practices.

PMID- 16084479
TI  - The neurodevelopmental consequences of prenatal alcohol exposure.
AB  - During pregnancy, ingestion of alcohol, a known teratogen, can cause harm to the
      fetus. Prenatal alcohol exposure is one of the leading causes of birth defects,
      developmental disorders, and mental retardation in children. The fetal central
      nervous system is particularly vulnerable to alcohol; this vulnerability
      contributes to many of the long-term disabilities and disorders seen in
      individuals with prenatal alcohol exposure. Diagnoses associated with prenatal
      alcohol exposure include fetal alcohol syndrome (FAS), partial fetal alcohol
      syndrome, fetal alcohol effects, alcohol-related neurodevelopmental disorder, and
      alcohol-related birth defects. Once diagnosed, early intervention improves the
      long-term outcome of affected children. Without documentation of maternal alcohol
      use, a diagnosis, and consequently treatment, is often difficult to attain. It is
      imperative that nurses, physicians, and other healthcare providers become
      comfortable with obtaining a history of, and providing anticipatory guidance and
      counseling about, alcohol use.

PMID- 16084480
TI  - A parent's guide to prenatal alcohol exposure.

PMID- 16084482
TI  - [A rectovaginal giant haematoma. A rare complication of Longo procedure].
AB  - Complications of Longo procedure are well known: haemorrhages, stapling line
      stricture, anal venous thrombosis below stapling line, perirectal abscess. A very
      large haematoma of the rectovaginal wall, with severe anaemia and urinary
      retention was never published to our knowledge.

PMID- 16084483
TI  - [Treatment of malignant intestinal obstruction. A prospective study over 80
      cases].
AB  - AIM: Of the work: evaluation of a multidisciplinary strategy and a prospective
      medicosurgical protocol for the treatment of occlusion due to unresectable
      peritoneal carcinomatosis. PATIENTS AND METHODS: All the included patients had
      occlusion and intraabdominal carcinomatosis. None could benefit a curative
      treatment. 75 patients were included for 80 episodes of intestinal obstruction.
      The protocol involved three successive therapeutic phases. (i) Treatment during
      five days by corticosteroids associated to antiemetic agents, anticholinergic
      antisecretory agents, and analgesics as needed (Phase I); (ii) In the event of
      refractory occlusive symptoms treatment by somatostatin analog during 3 days
      (phase II); (iii) If this treatment was ineffective a gastrostomy was performed
      (phase III). RESULTS: Median survival was 31 days. Outcome showed that for the 80
      episodes of obstruction, phase I medical treatment enabled relief in 50 cases
      (63%) and phase II medical treatment (somatostatin) enabled relief in 11 cases
      (14%). 10 more patients (13%) were relieved by the gastrostomie and one by a
      duodenal endoprothesis. Symptom control without a long-term nasogastric tube was
      achieved for 72 of the 80 episodes (90%). Fifty-eight episodes (72% of overall
      total) were controlled for 10 days or less. Median time to gastrostomy was 17
      days. Eight patients experienced persistent vomiting and required a nasogastric
      aspiration until death. CONCLUSION: This multidisciplinary approach between
      Palliative Care and Specialized Medical and Surgical teams enabled relief of the
      occlusive symptoms for 90% of the patients of the study. The protocol was useful
      for the caregivers for the management of terminally ill patients. To enhance
      these results, it would be necessary to shorten the delay of relief, which has
      been longer than ten days for one third of the patients. The simplification of
      the protocol including two steps instead of three is on study.

PMID- 16084484
TI  - [Gastrojejunocolic fistula, report of two recent cases with original management].
AB  - Gastrojejunocolic fistulae, ultimate complication of anastomotic peptic
      ulceration, are presently uncommon. We report two recent cases of postoperative
      gastrojejunocolic fistulas (after duodenal ulcer surgery and total
      duodenopancreatectomy), which were complicated at time of diagnosis (acute
      peritonitis and liver cirrhosis) and required a two-stage treatment.

PMID- 16084485
TI  - Uncoupling protein 3 protects aconitase against inactivation in isolated skeletal
      muscle mitochondria.
AB  - Mitochondrial uncoupling proteins only catalyse proton transport when they are
      activated. Activators include superoxide and reactive alkenals, suggesting new
      physiological functions for UCP2 and UCP3: their activation by superoxide when
      protonmotive force is high causes mild uncoupling, which lowers protonmotive
      force and attenuates superoxide generation by the electron transport chain. This
      feedback loop acts to prevent excessive mitochondrial superoxide production.
      Superoxide inactivates aconitase in the mitochondrial matrix, so aconitase
      activity provides a sensitive measure of the effects of UCPs on matrix
      superoxide. We find that inhibition of UCP3 in isolated skeletal muscle
      mitochondria by GDP decreases aconitase activity by 25% after 20 min incubation.
      The GDP effect is absent in skeletal muscle mitochondria from UCP3 knockout mice,
      showing that it is mediated by UCP3. Protection of aconitase by UCP3 in the
      absence of nucleotides does not require added fatty acids. The purine nucleoside
      diphosphates and triphosphates cause aconitase inactivation, but the
      monophosphates and CDP do not, consistent with the known nucleotide specificity
      of UCP3. The IC(50) for GDP is about 100 microM. These findings support the
      proposal that UCP3 attenuates endogenous radical production by the mitochondrial
      electron transport chain at high protonmotive force.

PMID- 16084486
TI  - Effects of a transition from normoxia to anoxia on yeast cytochrome c oxidase and
      the mitochondrial respiratory chain: implications for hypoxic gene induction.
AB  - Previous studies have demonstrated that the mitochondrial respiratory chain and
      cytochrome c oxidase participate in oxygen sensing and the induction of some
      hypoxic nuclear genes in eukaryotes. In addition, it has been proposed that
      mitochondrially-generated reactive oxygen and nitrogen species function as
      signals in a signaling pathway for the induction of hypoxic genes. To gain
      insight concerning this pathway, we have looked at changes in the functionality
      of the yeast respiratory chain as cells experience a shift from normoxia to
      anoxia. These studies have revealed that yeast cells retain the ability to
      respire at normoxic levels for up to 4 h after a shift and that the mitochondrial
      cytochrome levels drop rapidly to 30--50% of their normoxic levels and the
      turnover rate of cytochrome c oxidase (COX) increases during this shift. The
      increase in COX turnover rate cannot be explained by replacing the aerobic
      isoform, Va, of cytochrome c oxidase subunit V with the more active hypoxic
      isoform, Vb. We have also found that mitochondria retain the ability to respire,
      albeit at reduced levels, in anoxic cells, indicating that yeast cells maintain a
      functional mitochondrial respiratory chain in the absence of oxygen. This raises
      the intriguing possibility that the mitochondrial respiratory chain has a
      previously unexplored role in anoxic cells and may function with an alternative
      electron acceptor when oxygen is unavailable.

PMID- 16084487
TI  - Preparation and in vivo evaluation of PEGylated spherulite formulations.
AB  - Spherulites are multilamellar vesicles obtained by shearing a lamellar phase of
      lipids and surfactants. They consist of concentric bilayers of amphiphiles
      alternating with layers of aqueous medium in which hydrophilic drugs can be
      sequestered with high yield. To be useful for drug targeting applications,
      spherulites should be small and long circulating. The objectives of this work
      were threefold. First, the spherulite size was optimized to obtain a mean
      diameter of less than 300 nm. Second, the vesicle composition was adjusted to
      minimize in vitro leakage of internal content. Third, the spherulites were coated
      with 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine-N-[methoxy
      poly(ethylene glycol)] (DSPE-PEG) to impart them with a long half-life. Then, the
      PEGylated spherulites (Phospholipon 90G/Solutol HS15/cholesterol/DSPE-PEG 2000 or
      5000) were loaded with 1-beta-d-arabinofuranosylcytosine (ara-C) and injected
      intravenously to rats. They were compared to uncoated spherulites and to an ara-C
      solution. The surface-modified vesicles exhibited long circulation times with
      areas under the blood concentration vs. time curve exceeding by 3.1- to 6.9-fold
      that of uncoated spherulites. Similarly, blood levels of ara-C encapsulated in
      PEGylated vesicles were higher than those of the controls, but they did not
      parallel the carrier pharmacokinetics. Two hours post-injection, most of the drug
      was cleared from the systemic circulation, reflecting rapid leakage of ara-C from
      the vesicles.

PMID- 16084488
TI  - A pilot study of two-day cognitive-behavioral therapy for panic disorder.
AB  - The present study investigated the short-term efficacy of brief, intensive
      cognitive-behavioral therapy (CBT) for panic disorder (PD). The treatment
      involved 9h of therapist contact over two consecutive days and was developed for
      the purpose of delivering CBT for PD to a largely rural patient population that
      must travel long distances to find a treatment provider. Ten patients who elected
      to participate in brief, intensive CBT instead of weekly CBT were recruited from
      routine clinical practice in a hospital-based anxiety disorders clinic. Patients
      were not excluded based on the presence of agoraphobia, diagnostic comorbidity,
      concurrent use of PRN benzodiazepine medications, or previous nonresponse to
      psychotherapy for PD. Assessments conducted at pre-treatment and 1-month follow
      up revealed large, clinically significant reductions in PD symptoms, anxiety
      sensitivity, body vigilance, and anxiety and depressive symptoms. Most patients
      (60%) were panic-free after treatment and evidenced normative levels of
      symptomatology at follow-up. The present study suggests that brief, intensive
      treatment may be an effective means of delivering CBT for PD.

PMID- 16084489
TI  - Sequential induction of prostaglandin E and D synthases in inflammation.
AB  - Enhanced biosynthesis of prostaglandin (PG)D(2) and subsequent formation of 15
      deoxy-Delta(12,14)-PGJ(2) has been suggested to contribute to resolution of
      inflammation. The primary aim of the present study in mouse heart was, therefore,
      to determine at the transcriptional level if there is sequential induction of PGE
      and PGD synthases (S) during inflammation. Expression of interleukin (IL)-1beta
      in heart was enhanced 4h after systemic inflammation and declined thereafter
      within 3-5 days to basal levels. In contrast to cyclooxygenase-2 and membrane
      bound (m)-PGES-1, which both peaked 4h after endotoxin administration,
      hematopoietic (H)-PGDS expression was enhanced only >or=48h after endotoxin. The
      expression of lipocalin-type (L)-PGDS was not significantly influenced. mRNA
      encoding the putative target of 15-deoxy-Delta(12,14)-PGJ(2), peroxisome
      proliferator-activated receptor gamma, was enhanced between 4 and 24h after
      induction of inflammation. Treatment of mice with acetylsalicylic acid or
      indomethacin at doses effective to cause near-complete inhibition of PGE(2) and
      PGD(2) biosynthesis in heart ex vivo resulted in enhanced expression of IL-1beta
      24h after endotoxin administration. These results provide additional support for
      the hypothesis of a shift towards PGD(2) biosynthesis during resolution of
      inflammation.

PMID- 16084490
TI  - Characterization of endothelial progenitor cells.

PMID- 16084491
TI  - Interleukin-10 promoter gene polymorphisms have no clear influence on interleukin
      10 protein secretion in AIDS-associated B-cell lines.
AB  - Interleukin-10 (IL-10) is a pleiotropic cytokine involved in several immune
      responses and expressed by a variety of cell types. IL-10 interacts with at least
      two subunits of the IL-10 receptors (IL-10R1 and IL-10R2), which are members of
      the interferon receptor family, and play important roles in ligand binding and
      signaling. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and
      enzyme-linked immunosorbent assay (ELISA) methods, the mRNA expression and
      secretion patterns of IL-10 were studied. IL-10R1 and IL-10R2 mRNA expression
      patterns were also studied in the tumor-derived human B-cell lines. IL-10 protein
      is expressed and predominantly secreted by AIDS-associated B-cell lines (AABCL).
      However, IL-10R1 and IL-10R2 are constitutively and ubiquitously expressed in all
      the B-cell lines included in our study. These results suggest that B-cell IL-10
      functions as an autocrine growth factor, in AABCL. Furthermore, we report that
      higher secretion of IL-10 observed in AABCL could be due to the specific GCC
      haplotype of IL-10 promoter polymorphisms, although no specific correlation was
      observed between IL-10 promoter polymorphisms and IL-10 protein secretion as
      analyzed by PCR-sequence specific primers methodology and ELISA, respectively.

PMID- 16084492
TI  - Activation of chemokine receptor CXCR4 in malignant glioma cells promotes the
      production of vascular endothelial growth factor.
AB  - Numerous studies have showed that chemokine receptors, such as CXCR4, contribute
      to the growth and metastasis of a variety of malignant tumors. In this study, we
      investigated the role of CXCR4 in the production of angiogenic factor, vascular
      endothelial growth factor (VEGF), in various human glioma cells from astrocytic
      origin. The expression of CXCR4 mRNA and protein in three glioma cell lines, U87
      MG, SHG-44, and CHG-5, was determined by RT-PCR and immunocytochemistry,
      respectively. The malignancies of three gliomas were evaluated by expression of
      glial fibrillary acidic protein and vimentin, the differentiation markers of
      astrocytic cells. The role of functional CXCR4 in tumor cell migration was
      studied with chemotaxis assay. Ca2+ mobilization and VEGF production were
      measured in the cells after stimulation with CXCR4 ligand, SDF1beta. The results
      showed that the levels of functional CXCR4 expression at both mRNA and protein
      levels by several human glioma cell lines were correlated with the degree of
      differentiation of the tumor cells. Activation of CXCR4 induced glioma cell
      chemotaxis and could trigger the increase of intracellular [Ca2+]i. Such an
      activation could result in the increased production of VEGF by the stimulated
      tumor cells. Our results suggest that CXCR4 may contribute to the high level of
      VEGF produced by malignant glioma cells and thus constitute a therapeutic target
      for antiangiogenesis strategy.

PMID- 16084493
TI  - Anti-apoptotic role of retinoic acid in the inner ear of noise-exposed mice.
AB  - Exposure to loud noise can induce temporary or permanent hearing loss, and
      acoustic trauma is the major cause of hearing impairment in industrial nations.
      However, the mechanisms underlying the death of hair cells after acoustic trauma
      remain unclear. In addition to its involvement in cellular stress and apoptosis,
      the c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein
      kinase family, is involved in cell survival, transformation, embryonic
      morphogenesis, and differentiation. JNK is primarily activated by various
      environmental stresses including noise, and the phenotypic result appears be to
      cell death. All-trans retinoic acid (ATRA) is an active metabolite of vitamin A
      that regulates a wide range of biological processes, including cell
      proliferation, differentiation, and morphogenesis. We evaluated the role of ATRA
      in preserving hearing in mice exposed to noise that can induce permanent hearing
      loss. Mice fed with ATRA before and during 3 consecutive days of noise exposure
      had a more preserved hearing threshold than mice fed sesame oil or saline.
      Histological and TUNEL staining of the cochlea showed significantly enhanced
      preservation of the organ of Corti, including outer hair cells and relatively low
      apoptotic nuclei, in mice-fed ATRA than in mice-fed sesame oil or saline. Phospho
      JNK immunohistochemistry showed that ATRA inhibited the activation of JNK. These
      results suggest that ATRA has an anti-apoptotic effect on cochleae exposed to
      noise.

PMID- 16084494
TI  - Design, engineering, and characterization of zinc finger nucleases.
AB  - Zinc finger nuclease (ZFN)-mediated gene targeting is rapidly becoming a powerful
      tool for "gene editing" and "directed mutagenesis" of plant and mammalian genomes
      including the human genome. ZFN-mediated gene targeting provides molecular
      biologists with the ability to site-specifically manipulate and permanently
      modify plant and mammalian genomes. Facile production of ZFNs and rapid
      characterization of their in vitro sequence-specific cleavage properties are a
      pre-requisite before ZFN-mediated gene targeting can become an efficient and
      effective practical tool for widespread use in biotechnology. Here, we report the
      design, engineering, and rapid in vitro characterization of ZFNs that target
      specific endogenous sequences within two mouse genes (mTYR and mCFTR), and two
      human genes (hCCR5 and hDMPK), respectively. These engineered ZFNs recognize
      their respective cognate DNA sites encoded in a plasmid substrate in a sequence
      specific manner and, as expected, they induce a double-strand break at the chosen
      target site.

PMID- 16084495
TI  - Calmodulin physically interacts with the erythropoietin receptor and enhances
      Jak2-mediated signaling.
AB  - Stimulation of the erythropoietin receptor (EpoR) induces a transient increase in
      intracellular Ca2+ level as well as activation of the Jak2 tyrosine kinase to
      stimulate various downstream signaling pathways. Here, we demonstrate that the
      universal Ca2+ receptor calmodulin (CaM) binds EpoR in a Ca2+-dependent manner in
      vitro. Binding studies using various EpoR mutants in hematopoietic cells showed
      that CaM binds the membrane-proximal 65-amino-acid cytoplasmic region (amino
      acids 258-312) of EpoR that is critical for activation of Jak2-mediated EpoR
      signaling. Structurally unrelated CaM antagonists, W-13 and CMZ, inhibited
      activation of Jak2-mediated EpoR signaling pathways, whereas W-12, a W-13 analog,
      did not show any significant inhibitory effect. Moreover, overexpression of CaM
      augmented Epo-induced tyrosine phosphorylation of the EpoR. W-13, but not W-12,
      also inhibited Epo-induced proliferation and survival. Together, these results
      indicate that CaM binds to the membrane-proximal EpoR cytoplasmic region and
      plays an essential role in activation of Jak2-mediated EpoR signaling.

PMID- 16084496
TI  - Schisandrin B--a novel inhibitor of P-glycoprotein.
AB  - P-glycoprotein-mediated drug efflux is one of the major causes of the cancer
      multidrug resistance (MDR). Inhibition of P-glycoprotein could reverse cancer
      MDR. Here, we show that schisandrin B, a naturally occurring compound from
      Schisandra chinensis (Turcz.) Baill, bears strong potency to inhibit P
      glycoprotein. Schisandrin B reversed the drug resistance of four MDR cell lines
      characterized with overexpression of P-glycoprotein and fully restored the
      intracellular drug accumulation by interacting with P-glycoprotein. Schisandrin B
      has a core structure of dibenzocyclooctadiene, representing a novel P
      glycoprotein inhibitor. To our best knowledge, the role of schisandrin B to
      inhibit P-glycoprotein has not been reported.

PMID- 16084498
TI  - Effects of ghrelin on hypothalamic glucose responding neurons in rats.
AB  - Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHS
      R) with potent stimulatory effects on food intake. The aim of the present study
      was to investigate the effects of ghrelin on neuronal activity of hypothalamic
      glucose responding neurons. Single unit discharges in the lateral hypothalamic
      area (LHA), the ventromedial hypothalamic nucleus (VMH), and the parvocellular
      part of the paraventricular nucleus(pPVN) were recorded extracellularly by means
      of four-barrel glass micropipettes in anesthetized rats. The activity of glucose
      sensitive neurons (GSNs) in the LHA, pPVN, and of glucoreceptor neurons (GRNs) in
      the VMH modulated by administration of ghrelin was analyzed. In the LHA, the
      majority of GSNs (17/25) increased in frequency due to ghrelin. Whereas the
      majority of VMH-GRNs (27/33) and pPVN-GSNs (9/13) was inhibited. The responses to
      ghrelin were abolished by pretreatment of [D-Lys-3]-GHRP-6, ghrelin receptor
      antagonist. These data indicate that the glucose responding neurons in the LHA,
      VMH, and pPVN are also involved in the orexigenic actions of ghrelin in the
      hypothalamic circuits, although AgRP/NPY neurons in the arcuate nucleus (ARC) are
      the primary targets of ghrelin.

PMID- 16084497
TI  - DARPP-32 phosphorylation opposes the behavioral effects of nicotine.
AB  - BACKGROUND: The addictive properties of nicotine are mediated via dopaminergic
      pathways and their post-synaptic neurons in the striatum. Because post-synaptic
      neurons within the striatum contain high levels of the dopamine- and cAMP
      regulated phosphoprotein of 32 kDa (DARPP-32), we hypothesized that DARPP-32 may
      functionally contribute to the behavioral effects of nicotine. METHODS: We
      examined the behavioral effects of nicotine and the phosphorylation state of
      DARPP-32 in wild-type (WT) and DARPP-32 knockout (KO) mice. In one experiment, we
      assessed voluntary nicotine intake (0-50 microg/ml) of WT and KO mice in a two
      bottle choice paradigm. In a separate experiment, the motor-depressant effects of
      acute and repeated nicotine injections (0-.8 mg/kg, subcutaneously [SC]) were
      assessed. The phosphorylation of DARPP-32 at threonine34 and threonine75 were
      examined using Western blotting. RESULTS: A heightened responsiveness to nicotine
      was seen in KO mice when compared with WT mice in oral intake and motor
      depression. The enhanced responsiveness in KO mice was not due to alterations in
      taste sensations, fluid intake, or blood nicotine or cotinine levels. Systemic
      injections of nicotine resulted in increased striatal DARPP-32 phosphorylation at
      threonine34 and threonine75. CONCLUSIONS: DARPP-32 opposes the behavioral effects
      of nicotine possibly via concurrent phosphorylation at the two threonine sites.

PMID- 16084499
TI  - Molecular changes in nNOS protein expression within the ventrolateral medulla
      following transient focal ischemia affect cardiovascular functions.
AB  - The majority of human strokes involve an occlusion of the middle cerebral artery
      and subsequent damage to the brain tissues it perfuses. We have previously
      reported that reflex cardiovascular changes during a static muscle contraction
      are attenuated following transient middle cerebral artery occlusion (MCAO) and
      reperfusion [A. Ally, S.M. Nauli, T.J. Maher, Cardiovascular responses and
      neurotransmission in the ventrolateral medulla during skeletal muscle contraction
      following transient middle cerebral artery occlusion and reperfusion, Brain Res.
      952 (2002) 176-187]. We hypothesized that the attenuation is a result of altered
      expression of neuronal nitric oxide synthase (nNOS) within the rostral (RVLM) and
      caudal ventrolateral medulla (CVLM). In this study, we have compared
      cardiovascular responses and nNOS protein expression within the four quadrants,
      i.e., left and right sides of both RVLM and CVLM in sham-operated rats (n = 10)
      and in rats with a temporary 90-min left-sided MCAO followed by 24 h reperfusion
      (n = 10). Increases in mean arterial pressure during a static muscle contraction
      were significantly attenuated in MCAO rats when compared to sham rats. The
      transient ischemia reduced nNOS expression within the ipsilateral RVLM quadrant
      compared to the contralateral RVLM or RVLM quadrants of control rats. In
      contrast, compared to sham rats and the right CVLM quadrant of MCAO rats, nNOS
      expression was significantly augmented in the ipsilateral CVLM in left-sided MCAO
      rats. These data suggest that the attenuation of cardiovascular responses during
      static muscle contraction in MCAO rats is partly due to a reduction in nNOS
      expression within the ipsilateral RVLM and an overexpression of nNOS abundance
      within the ipsilateral CVLM. Results demonstrate that nNOS expression within the
      medulla plays a significant role in mediating cardiovascular responses during
      static exercise in intact and pathophysiological conditions.

PMID- 16084500
TI  - GM1 and ERK signaling in the aged brain.
AB  - We investigated the ability of GM1 to induce phosphorylation/activation of the
      extracellular-regulated protein kinases (ERKs) in the striatum, hippocampus and
      frontal cortex of aged male Sprague-Dawley rats. Three different treatment
      paradigms were used: a single application of GM1 to brain slices in situ, a
      single intracerebroventricular (icv) administration of GM1 in vivo, and chronic
      administration of GM1 in vivo. In situ, GM1 induced a rapid and transient
      activation of ERK1 and ERK 2 in both young and aged rats, and a similar effect
      was observed after stimulation with the neurotrophins NGF and BDNF. The aged
      brain appeared to respond more robustly to neurotrophic stimulation with the
      pERK2 response being significantly greater in the hippocampus and frontal cortex.
      Acute icv administration of GM1 resulted in short-lasting phosphorylation of ERKs
      in both aged groups, while chronic administration of GM1 induced a protracted
      phosphorylation of ERKs. Following chronic GM1 treatment, pERK2 levels in the
      aged hippocampus were elevated over young control animals. In agreement with
      reports that GM1 phosphorylates TrkA in vitro or in situ, treatment with GM1
      increased the phosphorylation of TrkA in hippocampus of both young and aged
      animals. These observations indicate that the aged brain maintains the ability to
      respond to neurotrophic stimuli and put forward the proposition that the ERK
      cascade is associated with the action(s) of GM1 ganglioside in vivo.

PMID- 16084501
TI  - The management of midline transcranial nasal dermoid sinus cysts.
AB  - The most common congenital midline nasal masses are nasal dermoid sinus cysts
      (NDSC) [Hughes GB, Sharpino G, Hunt W, Tucker HM. Management of the congenital
      midline nasal mass--a review. Head Neck Surg 1980;2:222-33.]. Their clinical
      importance hinges on their potential to communicate with the central nervous
      system. Preoperative diagnosis of an intracranial extension allows for referral
      to a craniofacial team with the appropriate skills and experience for a
      transcranial approach. All patients with a NDSC require imaging with high
      resolution multiplanar MRI scans and complimentary fine cut CT scan to reveal the
      anatomical extent of the tract and its relationship to the anterior cranial
      fossa. A single-stage craniofacial approach to resection of midline NDSC
      extending to the anterior cranial base is effective with minimal morbidity
      [Yavuzer R, Bier U, Jackson IT. Be careful: it might be a nasal dermoid cyst.
      Plast Reconstr Surg 1999;103:2082-3; Denoyelle F, Ducroz V, Roger G, Garabedian
      EN. Nasal dermoid sinus cysts in children. Laryngoscope 1997;107:795-800; Rohrich
      RJ, Lowe JB, Schwartz MR. The role of open rhinoplasty in the management of nasal
      dermoid cysts. Plast Reconstr Surg 1999;104:2163-70; Rahbar R, Shah P, Mulliken
      JB, et al. The presentation and management of nasal dermoid-a 30-year experience.
      Arch Otolaryngol Head Neck Surg 2003;129:464-71; Posnick JC, Bortoluzzi P,
      Armstrong DC, Drake JM. Intracranial nasal dermoid sinus cysts: computed
      tomographic scan findings and surgical results. Plast Reconstr Surg 1994;93:745
      54 [discussion 755-56]; Bartlett SP, Lin KY, Grossman R, Kratowitz J. The
      surgical management of orbitofacial dermoids in the pediatric patient. Plast
      Reconstr Surg 1993;91:1208-15.]. The cyst and tract are accessed through a
      combination of a nasal and transcranial approach. This allows visualisation and
      dissection of the tract with only a small incision on the nasal dorsum to include
      the cutaneous punctum when present. Transnasal endoscopic techniques have been
      advocated where the dermoid is located within the nasal cavity and there is
      little or no cutaneous involvement [Weiss DD, Robson CD, Mulliken JB. Transnasal
      endoscopic excision of midline nasal dermoid from the anterior cranial base.
      Plast Reconstr Surg 1998;101:2119-23.]. We present a review of five cases
      referred to our unit between 1999 and 2004 with a diagnosis of a midline nasal
      dermoid sinus cyst and radiological evidence of intracranial communication. All
      cases had a communication with the anterior cranial fossa diagnosed
      preoperatively and were treated surgically with a craniofacial approach. An
      intracranial extension was identified at operation in each case and this was
      confirmed on histopathology. The only significant complication resulted from an
      early postoperative infection, requiring re-operation. There were no recurrences
      and acceptable aesthetic outcomes have been observed in all cases.

PMID- 16084504
TI  - Regioselective synthesis of long-chain ethers and their sulfates derived from
      methyl beta-D-galactopyranoside and derivatives via dibutylstannylene acetal
      intermediates.
AB  - A number of different conditions were investigated for the alkylation of the
      dibutylstannylene acetals of methyl beta-d-galactopyranoside with long-chain
      primary alkyl bromides, decyl, dodecyl, and tetradecyl bromide. The best yields
      of the major products, the 3-O-alkyl ethers, were obtained by reaction of the
      alkyl bromide with the monodibutylstannylene acetal in DMF in the presence of
      cesium fluoride for extended periods of time at moderate temperatures (65 degrees
      C). These products were always accompanied by minor amounts of the 3,6-di-O-alkyl
      derivative. Performing the reaction with excess alkyl halide on the
      bis(dibutylstannylene) acetal resulted in more of the 3,6-di-O-alkyl derivative,
      particularly for the shorter alkyl bromides, but this product was never
      predominant. Sulfation of the dibutylstannylene acetal of methyl 3-O-tetradecyl
      beta-D-galactopyranoside resulted in the 6-sulfate in 96% yield.

PMID- 16084505
TI  - Successful cryopreservation of Pacific oyster (Crassostrea gigas) oocytes.
AB  - Protocols for cryopreservation of sperm and oocytes would provide the ultimate
      control over parental crosses in selective breeding programmes. Sperm freezing is
      routine for many species, but oocyte freezing remains problematic, with virtually
      zero success in aquatic species to date. This paper describes the development of
      a successful protocol for cryopreserving high concentrations of Pacific oyster
      (Crassostrea gigas) oocytes. Ethylene glycol (10%) and dimethyl sulfoxide (15%)
      were found to be the most effective cryoprotectants resulting in post-thaw
      fertilization rates of 51.0+/-8.0 and 45.1+/-8.3%, respectively. Propylene glycol
      was less effective and methanol resulted in zero fertilization post-thaw. The use
      of Milli-Q water rather than seawater as a base medium significantly improved
      fertilization (20.4+/-3.0 and 8.7+/-2.2%, respectively) as did the inclusion of a
      5 min isothermal hold at -10 or -12 degrees C (35.9+/-5.0 and 31.9+/-4.6%,
      respectively). The optimal cooling rate post-hold was 0.3 degrees C min(-1), with
      virtually zero post-thaw fertilization with cooling rates of 3 and 6 degrees C
      min(-1). Using an optimized protocol, post-thaw fertilization rates for oocytes
      from eight individual females ranged from 0.8 to 74.5% and D-larval yields from
      0.1 to 30.1%. For three individuals, larvae were reared through to spat.
      Development of D-larvae to eyed larvae and spat was similar for larvae produced
      from unfrozen (24.8+/-4.1% developed to eyed larvae and 16.5+/-3.2% to spat) and
      cryopreserved (28.4+/-0.6 and 18.7+/-0.5%, respectively) oocytes. The ability to
      cryopreserve large quantities of oyster oocytes represents a major advance in
      cryobiology and selective breeding.

PMID- 16084506
TI  - achaete, but not scute, is dispensable for the peripheral nervous system of
      Drosophila.
AB  - The achaete-scute complex of Drosophila has been the focus of extensive genetic
      and developmental analysis. Of the four genes at this locus, achaete and scute
      appear to act redundantly to specify the peripheral nervous system. They share
      cis-regulatory elements and are co-expressed at the same locations. A mutation
      removing scute activity has been previously described; it causes a loss of some
      sensory bristles. Thus, when Scute is absent, the activity of achaete allows
      formation of the remaining bristles. However, all existing achaete mutants are
      rearrangements affecting regulatory sequences common to both achaete and scute.
      To determine the level of redundancy between the two genes, we have used a P
      element approach to generate a null allele of achaete, which leaves scute and all
      cis-regulatory elements intact. We find that the peripheral nervous system of
      achaete null mutant larvae and imagos lacks any detectable phenotype. However,
      when the levels of Scute are limiting, then some sensory organs are missing in
      achaete mutant flies. achaete and scute are thought to have arisen from a
      duplication event about 100 Myr ago. The difference between achaete and scute
      null flies is surprising and raises the question of the retention of both genes
      during the course of evolution.

PMID- 16084507
TI  - Heterogeneity of NG2-expressing cells in the newborn mouse cerebellum.
AB  - The function and origin of NG2+ cells in the adult brain are still controversial.
      A large amount of data is available which strongly indicates that adult NG2
      expressing cells form a heterogeneous population, constituted by oligodendrocyte
      precursor cells (OPCs) and a fourth novel type of glial cells named the
      synantocytes. Whether these two populations derive from the progressive
      maturation of perinatal NG2+ OPCs or are generated as separate populations is not
      known. We used organotypic cultures of newborn mouse cerebellum depleted, by anti
      mitotic drug treatment, of their NG2+ cells with perinatal features (high
      proliferating rate and high oligodendrocytic differentiation ability). In these
      cultures, despite the lack of myelin after 14 days in vitro, numerous NG2+ cells
      remained. We show that these BrdU-resistant cells were able to slowly divide, as
      adult NG2+ cells do. Although many of these cells expressed O4, only a very small
      fraction of them was further engaged in oligodendrocyte lineage, as they had an
      extremely poor capacity to generate myelin sheaths to the Purkinje cell axons.
      These results support the view that at least two distinct populations of NG2+
      cells coexist in the cerebellum from birth: one with the young OPC
      characteristics, another with adult NG2+ cell characteristics. Thus, a fraction
      of adult NG2+ cells do not derive from the maturation of perinatal OPCs.

PMID- 16084508
TI  - The Wnt effector POP-1 and the PAL-1/Caudal homeoprotein collaborate with SKN-1
      to activate C. elegans endoderm development.
AB  - POP-1, a Tcf/Lef-1-like target of the convergent Wnt and MAP kinase (MAPK)
      signaling pathways, functions throughout Caenorhabditis elegans development to
      generate unequal daughters during asymmetric cell divisions. A particularly
      prominent such asymmetric division occurs when the EMS blastomere divides to
      produce MS, a mesoderm precursor, and E, the sole endoderm progenitor. POP-1
      allows mesoderm development in the MS lineage by repressing the endoderm
      promoting end-1 and end-3 genes. This repression is relieved in the E lineage by
      Wnt/MAPK signaling, which results in phosphorylation and export of POP-1 from the
      E nucleus. Here, we report that, in addition to repressing E development in MS,
      POP-1 also functions positively in endoderm development, in conjunction with the
      well-characterized endoderm-promoting SKN-1-->MED regulatory cascade. While
      removal of POP-1 alone results in derepression of endoderm development in the MS
      lineage, mutations in several genes that result in impenetrant loss of endoderm
      are strongly enhanced by loss of pop-1 function. A Lef-1-like binding site is
      essential for activation of an end-1 promoter fusion, suggesting that POP-1 may
      act directly on end-1. Thus, POP-1 may generate developmental asymmetry during
      many cell divisions in C. elegans by reiteratively switching from repressive and
      activating states. Furthermore, we report that the Caudal-like homeodomain
      protein PAL-1, whose role in early embryogenesis was thought to be exclusive
      specification of mesectodermal development in the lineage of the C blastomere,
      can act with POP-1 to activate endoderm specification in the absence of the SKN-1
      ->MED transcriptional input, accounting for the impenetrance of mutants lacking
      SKN-1 or MED-1,2 activity. We conclude that the combined action of several
      separate transcriptional regulatory inputs, including SKN-1, the MEDs, PAL-1, and
      the Wnt/MAPK-activated form of POP-1, are responsible for activating end gene
      transcription and endoderm development.

PMID- 16084509
TI  - Effects of beta-adrenoceptor antagonists in the neural nitric oxide release
      induced by electrical field stimulation and sodium channel activators in the
      rabbit corpus cavernosum.
AB  - Beta-Adrenoceptor antagonists may present receptor-independent mechanisms, such
      as blockade of voltage-gated sodium channels. This study aimed to investigate the
      effects of non-selective (propranolol), and selective beta1- (atenolol,
      metoprolol and betaxolol) and beta2-adrenoceptor (ICI 118,551) antagonists in the
      nitric oxide (NO)-mediated rabbit corpus cavernosum relaxations induced by either
      electrical field stimulation (EFS) or activators of voltage-gated sodium
      channels. The sodium channel blockers tetrodotoxin and saxitoxin abolished the
      relaxations induced by EFS or sodium channel activators of binding site-2
      (aconitine and veratridine), site-3 (Ts3 toxin), site-4 (Ts1 toxin) and site-5
      (brevetoxin-3). The beta-adrenoceptor antagonists failed to affect the
      relaxations induced by EFS, aconitine and veratridine. Relaxations induced by Ts3
      and Ts1 toxins, as well as brevetoxin-3, were markedly reduced by prior addition
      of propranolol, betaxolol and ICI 118,551. During the established relaxation
      induced by Ts3 toxin, propranolol failed to restore the basal tone. In
      conclusion, beta-adrenoceptor antagonists may cause an allosteric inhibition at
      the binding site-3, -4 and -5 of voltage-gated sodium channels, leading to
      blockade of neural NO release.

PMID- 16084510
TI  - Gene expression profiling in response to the histone deacetylase inhibitor BL1521
      in neuroblastoma.
AB  - Neuroblastoma is a childhood tumor with a poor survival in advanced stage disease
      despite intensive chemotherapeutic regimes. The new histone deacetylase (HDAC)
      inhibitor BL1521 has shown promising results in neuroblastoma. Inhibition of HDAC
      resulted in a decrease in proliferation and metabolic activity, induction of
      apoptosis and differentiation of neuroblastoma cells. In order to elucidate the
      mechanism mediating the effects of BL1521 on neuroblastoma cells, we investigated
      the gene expression profile of an MYCN single copy (SKNAS) and an MYCN amplified
      (IMR32) neuroblastoma cell line after treatment with BL1521 using the Affymetrix
      oligonucleotide array U133A. An altered expression of 255 genes was observed in
      both neuroblastoma cell lines. The majority of these genes were involved in gene
      expression, cellular metabolism, and cell signaling. We observed changes in the
      expression of vital genes belonging to the cell cycle (cyclin D1 and CDK4) and
      apoptosis (BNIP3, BID, and BCL2) pathway in response to BL1521. The expression of
      37 genes was altered by both BL1521 and Trichostatin A, which could indicate a
      common gene set regulated by different HDAC inhibitors. BL1521 treatment changed
      the expression of a number of MYCN-associated genes. Several genes in the Wnt and
      the Delta/Notch pathways were changed in response to BL1521 treatment, suggesting
      that BL1521 is able to induce the differentiation of neuroblastoma cells into a
      more mature phenotype.

PMID- 16084512
TI  - Impaired spatial learning in a novel rat model of mild cerebral concussion
      injury.
AB  - The aim of the present study was to develop a model of mild traumatic brain
      injury in the rat that mimics human concussive brain injury suitable to study
      pathophysiology and potential treatments. 34 male Wistar rats received a closed
      head trauma (TBI) and 30 animals served as controls (CON). Immediately following
      trauma, animals lost their muscle tone and righting reflex response, recovering
      from the latter within 11.4 +/- 8.2 min. Corneal reflex and whisker responses
      returned within 4.5 +/- 3.0 min and 6.1 +/- 2.9 min, respectively. The impact
      resulted in a short transient decrease of pO2 (P < 0.001), increase in mean
      arterial blood pressure (P = 0.026), and a reduction of heart rate (P < 0.01).
      Serial MRI did not show any abnormalities across the entire cerebrum on
      diffusion, T1, T2, and T2*-weighted images at all investigated time points. TBI
      animals needed significantly longer to locate the hidden platform in a Morris
      water maze and spent less time in the training quadrant than controls. TBI led to
      a significant neuronal loss in frontal cortex (P < 0.001), as well as hippocampal
      CA3 (P = 0.017) and CA1 (P = 0.002) at 9 days after the trauma; however,
      cytoskeletal architecture was preserved as indicated by normal betaAPP- and MAP-2
      staining. We present a unique, noninvasive rat model of mild closed head trauma
      with characteristics of human concussion injury, including brief loss of
      consciousness, cognitive impairment, and minor brain injury.

PMID- 16084513
TI  - Spreading depression in the cortex differently modulates dopamine release in rat
      mesolimbic and nigrostriatal terminal fields.
AB  - The effects of cortical spreading depression (SD) on evoked dopamine release in
      mesolimbic (nucleus accumbens) and nigrostriatal (nucleus caudatus) terminal
      fields were studied by in vivo voltammetry in anesthetized rats. Dopamine release
      was evoked by electrical stimulation of medial forebrain bundle (20 Hz, 100
      pulses). Local application of 3 M KCl on the dura initiated SD in the cortex. It
      was found that SD modulated evoked dopamine release in subcortical structures at
      the same time when the wave of depression of cortical activity reached
      reciprocally connected subcortical areas. This cortical depression increased
      stimulated dopamine release in the nucleus accumbens and decreased dopamine
      release in the nucleus caudatus. In agreement with these results, electrical
      stimulation of the prefrontal cortex at 20 Hz, synchronized with medial forebrain
      bundle stimulation, decreased evoked dopamine release in the nucleus accumbens.
      Areas of the cortex which modulated dopamine release in these two terminal fields
      were spatially separated by at least 5 mm from each other. It is proposed that
      depression and activation of evoked dopamine release in the nucleus caudatus and
      nucleus accumbens following SD are indicative of tonic activation of the
      nigrostriatal and tonic inhibition of the mesolimbic dopaminergic terminals by
      cortex in normal conditions. SD in the cortex, modulating neurotransmitter
      release in subcortical structures, may have a general impact on redistribution of
      oxygen supply in these subcortical areas and on behavior associated with brain
      trauma, migraine, insult or seizures, i.e. the kind of neuropathology which may
      cause SD type phenomena also in human brain.

PMID- 16084511
TI  - Seizure susceptibility in intact and ovariectomized female rats treated with the
      convulsant pilocarpine.
AB  - Despite numerous neuroendocrinological studies of seizures, the influence of
      estrogen and progesterone on seizures and epilepsy remains unclear. This may be
      due to the fact that previous studies have not systematically compared distinct
      endocrine conditions and included all relevant controls. The goal of the present
      study was to conduct such a study using pilocarpine as chemoconvulsant. Thus, age
      and weight-matched, intact or ovariectomized rats were tested to determine
      incidence of status epilepticus and to study events leading to status. Intact
      female rats were sampled at each cycle stage (proestrus, estrus, metestrus, or
      diestrus 2). Convulsant was administered at the same time of day, 10:00-10:30
      a.m. Statistical analysis showed that there was a significantly lower incidence
      of status on the morning of estrus, but differences were attenuated in older
      animals. Ovariectomized rats were distinct in their rapid progression to status.
      These results show that the incidence of status in female rats following
      pilocarpine injection, and the progression to pilocarpine-induced status, are
      influenced by reproductive state as well as age. The hormonal milieu present
      specifically on the morning of estrus appears to decrease susceptibility to
      pilocarpine-induced status, particularly at young ages. In contrast, the chronic
      absence of reproductive steroids that characterizes the ovariectomized rat leads
      to a more rapid progression to status. This dissociation between incidence vs.
      progression provides new insight into the influence of estrogen and progesterone
      on seizures.

PMID- 16084514
TI  - Improved solubility and dissolution rate of piroxicam using gelucire 44/14 and
      labrasol.
AB  - Piroxicam is a nonsteroidal anti-inflammatory drug that is characterized by low
      solubility-high permeability. The present study was designed to improve the
      dissolution rate of piroxicam at the physiological pH's through its increased
      solubility by preparing semi-solid dispersions of drug using Gelucires and
      Labrasol. These excipients are essentially characterized by their melting points
      and HLB (hydrophilic-lipophilic balance) values. The dissolution tests of the
      preparations were performed in the media with different pH's. Differential
      scanning calorimetry (DSC), were used to examine the interaction between
      piroxicam and excipients. Gelucire 44/14 and Labrasol at the concentration of 15%
      w/v in water provided 20- and 50-fold increase in the solubility of piroxicam,
      respectively. The semi-solid dispersion containing 1/20 of drug/excipient mixture
      (20% Gelucire 44/14 and 80% Labrasol in w/w) produced the dissolution not less
      than 85% of piroxicam within 30 min in each dissolution media (simulated gastric
      fluid (SGF), pH 1.2; phosphate buffers, pH 4.5 and 6.8; and water). DSC analysis
      of this semi-solid dispersion indicated that there was no chemical reaction
      between the drug and excipients, and that a solid-state solution of piroxicam
      with excipient formed.

PMID- 16084515
TI  - Association of plasma eotaxin levels with the presence and extent of angiographic
      coronary artery disease.
AB  - Eotaxin (CCL11) is an eosinophil-specific chemoattractant which has been found to
      be highly expressed at sites of vascular pathology. In the present study, we
      aimed to evaluate the association of plasma eotaxin levels with the presence and
      extent of angiographic coronary artery disease (CAD). Three hundred and fifty six
      consecutive patients attending for elective coronary angiography were
      investigated. Compared with 111 patients without CAD, 245 with CAD showed higher
      eotaxin concentrations [median (interquartile range): 76.0 (56.3-103.0)pg/ml
      versus 116.0 (80.5-162.0)pg/ml, respectively; P<0.001]. Importantly, a
      significant Spearman correlation was found between eotaxin levels and the extent
      score of coronary artery stenosis (r=0.449, P<0.001). A stepwise increase in
      plasma levels of eotaxin was also found depending on the number of >50% coronary
      stenosis: median value 76.0 pg/ml in CAD(-) subjects, 96.0 pg/ml in 1-vessel
      disease, 128.0 pg/ml in 2-vessel disease, and 129.0 pg/ml in 3-vessel disease
      (P<0.001 for trend). After confounding variables were controlled for, multiple
      stepwise regression analysis demonstrated that plasma eotaxin was an independent
      predictor of angiographic extent of CAD (beta=0.426, P<0.001). Our data suggest
      that increased eotaxin levels are associated with the presence of CAD and that
      circulating levels of this chemokine may reflect the extent of coronary
      atherosclerosis.

PMID- 16084516
TI  - Effects of omega-3 fatty acids on coronary restenosis, intima-media thickness,
      and exercise tolerance: a systematic review.
AB  - Greater omega-3 fatty acid consumption is associated with reduced cardiovascular
      disease risk. Though the mechanisms of their effect are unclear, they may involve
      lesion formation and heart function. We conducted a systematic review of the
      clinical literature on the effect of omega-3 fatty acids on measures of vascular
      structure and function. We included studies that assessed fish and plant sources
      of omega-3 fatty acids on coronary artery restenosis after angioplasty, carotid
      IMT, and exercise capacity. Compared to placebo, the summary risk ratio of
      coronary artery restenosis with fish oil is 0.87 (95% CI 0.73, 1.05) across 12
      randomized controlled trials. Two prospective studies reported increased carotid
      IMT, whereas two cross-sectional studies reported a reduction of IMT, with fish,
      fish oil or ALA consumption. Three randomized trials and three uncontrolled
      studies reported small non-significant improvements in exercise capacity with
      fish oil. Overall, little or no effect of fish oil was found for a variety of
      markers of cardiovascular disease risk. There are insufficient studies to draw
      conclusions about the effect of ALA. The dearth of long term data on fish
      consumption or omega-3 fatty acid supplementation on measures of cardiovascular
      disease risk severely limits our ability to draw definitive conclusions at this
      time.

PMID- 16084517
TI  - Endurance training reduces circulating inflammatory markers in persons at risk of
      coronary events: impact on plaque stabilization?
AB  - Inflammatory pathways are involved in destabilization of atherosclerotic plaques.
      We assessed the hypothesis that endurance training decreases circulating
      concentrations of inflammatory markers in persons with coronary artery disease
      (CAD) and cardiovascular risk factors (CVRFs). Thirty-two subjects with CAD
      and/or CVRFs joined a 12-week supervised endurance training. We found a
      significant decrease of the chemokines interleukin (IL)-8 (pre: 3.9+/-0.6,
      change: -1.2+/-0.4 pg/ml, -21%, p=0.002) and monocyte chemoattractant protein-1
      (pre: 213+/-9, change: -20.4+/-8.2 pg/ml, -5%, p=0.03). Diabetes mellitus (DM)
      significantly influenced changes of IL-8 (p=0.002). IL-8 substantially dropped by
      39% in diabetics. Moreover, matrix metalloproteinase-9 (MMP-9) highly
      significantly decreased in response to training (pre: 750+/-98, change: -278+/-77
      ng/ml, -18%, p=0.005). Exercise-induced changes of MMP-9 were influenced by
      concomitant use of statins (p=0.038). We observed a particularly strong MMP-9
      reduction of 44% in patients treated with statins. Acute phase reactants IL-6
      (pre: 1.7+/-0.3, change: +0.25+/-0.7 pg/ml, +4%, p=0.58) and high sensitivity C
      reactive protein (pre: 2.1+/-0.5, change: -0.25+/-0.4 mg/l, -9%, p=0.54) did not
      change in response to training. In conclusion, endurance training decreased
      circulating chemokines and MMP-9, which may in part explain its beneficial effect
      on coronary risk. Patients with DM or treated with statins because of
      hypercholesterolemia may particularly take advantage.

PMID- 16084518
TI  - Mandibular stiffness in humans: numerical predictions.
AB  - The chin is a feature unique to humans. This study evaluates the effect of
      mandibular symphyseal design on biomechanical masticatory effectiveness as
      determined by structural stiffness and stress developed under flexural and
      torsional loading. A simple model of three symphyseal shapes (chin, flat
      symphysis and lingual buttress), was built to represent human, Neanderthal and
      higher primate symphyses and these were subjected to wishboning and torsional
      forces. Additionally, an anatomically detailed reconstruction was made of the CT
      scan of an actual human mandible, which was then also morphed into a chinless
      model. The results of a 3-D finite element analysis show firstly, that none of
      the three different symphyseal shapes is biomechanically more advantageous than
      the others for the given loading condition. Secondly, we show in a CT-derived
      model, that the presence of a chin does not confer significantly improved
      stiffness to torsional or flexural loading. These results indicate that the
      acquisition of a chin in modern humans is not related to the functional demands
      placed upon the mandible during mastication, but suggest that it may have
      developed in response to other biomechanical demands.

PMID- 16084519
TI  - Wall thickness of gas- and marrow-filled avian long bones: measurements on
      humeri, femora and tibiotarsi in crows (Corvus corone cornix) and magpies (Pica
      pica).
AB  - We studied how the ratio K of the internal to external diameter of gas- and
      marrow-filled avian long bones follows the biomechanical optima derived for
      tubular bones with minimum mass designed to fulfil various mechanical
      requirements. We evaluated radiographs of numerous humeri, femora and tibiotarsi
      in Corvus corone cornix and Pica pica. The K-values of the gas-filled humerus
      (K=0.78+/-0.03) and the marrow-filled femur (K=0.79+/-0.02) in Corvus are
      practically the same, while K of the marrow-filled tibiotarsus (K=0.71+/-0.04) is
      significantly smaller. The same is true for the gas-filled humerus (K=0.78+/
      0.02) and the marrow-filled femur (K=0.77+/-0.02) and tibiotarsus (K=0.67+/-0.05)
      in Pica. K in Corvus is slightly larger than K in Pica, but the differences are
      statistically not significant. The standard deviation DeltaK of the tibiotarsi
      (DeltaK=0.04-0.05) is approximately two times as large as that of the humeri
      (DeltaK=0.02-0.03) and femora (DeltaK=0.02) in both species. Accepting the
      assumption of earlier authors that the ratio Q of the marrow to bone density is
      0.5, our data show that the marrow-filled tibiotarsi of Corvus and Pica are
      optimized for stiffness, while the marrow-filled femora are far from any optimum.
      The relative wall thickness W=1-K of the gas-filled avian humeri studied is much
      larger than the theoretical optimum W*=1-K*=0.07, and thus these bones are
      thicker-walled than the optimal gas-filled tubular bone with minimum mass.

PMID- 16084520
TI  - Sensitivity of a Hill-based muscle model to perturbations in model parameters.
AB  - Musculoskeletal simulations of human movement commonly use Hill muscle models to
      predict muscle forces, but their sensitivity to model parameter values is not
      well understood. The purpose of this study was to evaluate muscle model
      sensitivity to perturbations in 14 Hill muscle model parameters in forward
      dynamic simulations of running and walking by varying each by +/-50%. Three
      evaluations of the muscle model were performed based on: (1) calculating the
      sensitivity of the muscle model only, (2) determining the continuous partial
      derivatives of the muscle equations with respect to each parameter, and (3)
      evaluating the effects on the running and walking simulations. Model evaluations
      were found to be very sensitive (percent change in outputs greater than parameter
      perturbation) to parameters defining the series elastic component (tendon), force
      length curve of the contractile element and maximum isometric force. For some
      parameters, the range of literature values was larger than the model sensitivity.
      Model evaluations were insensitive to parameters defining the parallel elastic
      element, force-velocity curve of the contractile element and muscle activation
      time constants. The derivative method provided similar results, but also provided
      a generic, continuous equation that can easily be applied to other motions. The
      sensitivities of the running and walking simulations were reduced compared to the
      sensitivity of the muscle model alone. Results demonstrate the importance of
      evaluating sensitivity of a musculoskeletal simulation in a controlled manner and
      provide an indication of which parameters must be selected most carefully based
      on the sensitivity of a given movement.

PMID- 16084521
TI  - Effect of various factors influencing the delamination behavior of surfactant
      intercalated layered double hydroxides.
AB  - The delamination-restacking behavior of a number of layered double hydroxides
      (LDHs) differing in [M(II)]/[M(III)] ratio, constituent metal ions and
      intercalated surfactant anions in different organic solvents has been studied.
      Colloidal dispersion due to delamination and the stability of the colloid
      obtained have been found to be not affected much by the nature of the constituent
      metal ions but increase with increase in the size of the surfactant anion. LDHs
      with low [M(II)]/[M(III)] ratio delaminate better than the ones with high
      [M(II)]/[M(III)] ratio. Delamination is best in alcohols such as 1-butanol, 1
      hexanol, 1-octanol and 1-decanol, while a little delamination occurs in nonpolar
      solvents such as hexane. In all the cases, the original layered solid could be
      obtained through restacking of layers from the colloidal dispersion.

PMID- 16084522
TI  - Studies on manganese nodule leached residue 4. Physicochemical characterization
      and catalytic activity of acetic acid treated manganese nodule leached residue.
AB  - The catalytic activity of water-washed manganese nodule leached residue (WMNLR)
      samples improved by treating with acetic acid. The effects of acetic acid
      treatment on the physicochemical properties and catalytic activity of manganese
      nodule leached residue have been studied. The surface area, surface oxygen,
      surface hydroxyl groups, surface acidity, electron donating properties, etc.,
      increase gradually with acid treatment up to 0.5 M and thereafter show a
      decreasing trend. The rate constant of H2O2 decomposition, catalytic activity of
      CO oxidation, and esterification of acetic acid also show a similar trend to that
      of surface properties.

PMID- 16084523
TI  - The validity of Cassie's law: a simple exercise using a simplified model.
AB  - The contact angle of a macroscopic droplet on a heterogeneous but flat substrate
      is studied using the interface displacement model which can lead to the augmented
      Young-Laplace equation. Droplets under the condition of constant volume as well
      as constant vapor pressure are considered. By assuming a cylindrical liquid-vapor
      surface (meniscus) and minimizing the total free energy of the interface
      displacement model, we derive an equation which is similar but different from the
      well-known Cassie's law. Our modified Cassie's law is essentially the same as the
      formula obtained previously by Marmur [J. Colloid Interface Sci. 168 (1994) 40].
      A few consequences from this modified Cassie's law are briefly described in the
      following sections of this paper. Several sets of recent experimental results
      seem to support the validity of our modified Cassie's law.

PMID- 16084524
TI  - Study of mass transfer in oil-water-oil multiple emulsions by differential
      scanning calorimetry.
AB  - A multiple emulsion of the type O1/W/O2 is studied experimentally by means of
      differential scanning calorimetry (DSC). The aim of this work is to characterize
      and measure the time-dependent changes within the emulsion. In particular,
      interest is focused to quantify the concentration changes in the internal and
      external phases of the O1/W/O2 multiple emulsion. In order to accomplish the
      objective, the measurement and analysis carried out by DSC are based on the
      crystallization behavior of the emulsion. A volume of a few mm3 is periodically
      removed from the O1/W/O2 multiple emulsion. The sample is submitted to steady
      cooling and the crystallization thermogram is recorded. The experimental data
      provided by the crystallization thermogram makes it possible to quantify the
      crystallized mass for both phases, the internal and the external. In addition,
      the composition in each phase can also be deduced from the thermogram. To deduce
      the composition, a diagram of crystallization temperatures is elaborated,
      employing several mixtures of known composition. In addition to the main
      objective previously mentioned, the influence of formulation parameters such as
      surfactant concentration in the aqueous phase and the mass ratio of the internal
      and external phases are also analyzed. The experimental results made it possible
      to conclude that a mass transfer took place from the internal phase toward the
      external phase; this transfer is caused by the composition difference on both
      sides of the aqueous membrane. In this work we analyzed the mass transfer in the
      multiple emulsion carried out by a composition gradient through the aqueous
      membrane. The most likely mechanism of mass transfer through the aqueous membrane
      is a solution-diffusion of tetradecane enhanced by the micelles of the surfactant
      Tween 20. The model of mass transfer confirms that the osmotic pressure
      difference controls the kinetics of tetradecane transfer. It is also confirmed
      that an increment of surfactant concentration in the aqueous phase allows a
      faster kinetics of the tetradecane transfer.

PMID- 16084525
TI  - Sub-monolayer growth by sequential deposition of particles.
AB  - We studied the various stages in the preparation of a sub-monolayer film by the
      sequential deposition of particles (sequential quenching model) from very low to
      very high temperatures, a limit at which the system becomes equivalent to random
      sequential adsorption. Due to the finite size of the simulation box, only one
      cluster can be found in a system at very low temperatures (T* = 0.01 and 0.1) and
      its size grows linearly with increasing density. At higher temperatures (T* = 0.3
      or higher), on the other hand, the same systems show a crossover from a
      nucleation regime to a growth regime. It is best revealed in a plot showing the
      distribution of monomers on the surface versus density, where the crossover
      region appears as a peak on a curve. At densities above the crossover, any new
      addition tends to contribute to the growth of an existing cluster rather than to
      nucleating new one.

PMID- 16084526
TI  - Crystal structure of the 13-cis isomer of bacteriorhodopsin in the dark-adapted
      state.
AB  - The atomic structure of the trans isomer of bacteriorhodopsin was determined
      previously by using a 3D crystal belonging to the space group P622. Here, a
      structure is reported for another isomer with the 13-cis, 15-syn retinal in a
      dark-adapted crystal. Structural comparison of the two isomers indicates that
      retinal isomerization around the C13[double bond]C14 and the C15[double bond]N
      bonds is accompanied by noticeable displacements of a few residues in the
      vicinity of the retinal Schiff base and small re-arrangement of the hydrogen
      bonding network in the proton release channel. On the other hand, aromatic
      residues surrounding the retinal polyene chain were found to scarcely move during
      the dark/light adaptation. This result suggests that variation in the structural
      rigidity within the retinal-binding pocket is one of the important factors
      ensuring the stereospecific isomerization of retinal.

PMID- 16084527
TI  - Calcineurin regulates enteric muscle contraction through EXP-1, excitatory GABA
      gated channel, in C. elegans.
AB  - The enteric muscle contraction (EMC) is the last step of the defecation behavior
      which occurs every 50 s in Caenorhabditis elegans. This EMC is regulated by
      intestinal and anal depressor muscles, which are innervated by GABA motor
      neurons. Our data show that calcineurin (tax-6) is expressed in intestinal muscle
      and anal depressor muscle, and the gain-of-function mutant of calcineurin, tax
      6(jh107), shows defects in enteric muscle contractions. In addition, the
      intracellular region of EXP-1, an excitatory GABA receptor, specifically binds to
      calcineurin A. This interaction between TAX-6 and EXP-1 appears to be independent
      of both calcium and CNB, which is the calcium-binding regulatory subunit. Genetic
      evidence of epistasis between cnb-1(jh103) and exp-1(sa6) suggests that
      calcineurin functions as a negative regulator of excitatory GABA receptor in GABA
      signaling in C.elegans.

PMID- 16084528
TI  - Reduced prefrontal N-acetylaspartate in stroke patients with apathy.
AB  - BACKGROUND: Although substantial numbers of stroke patients suffer from apathy,
      its causes are still poorly understood. Previous studies suggest that dysfunction
      of the frontal lobes is implicated in the pathophysiology of motivation. Our aim
      was to investigate the association between proton magnetic resonance spectroscopy
      (H1-MRS) measurements in unaffected frontal lobes and apathy in a group of first
      time stroke patients. METHODS: 31 patients with a first-time ischemic stroke
      located outside the frontal lobes and 20 healthy subjects were included in the
      study. The authors performed single voxel H1-MRS in order to measure the N
      acetylaspartate/creatine (NAA)/Cr, glutamate+glutamine (Glx)/Cr, choline (Cho)/Cr
      and myo-inositol (mI)/Cr ratios in the frontal lobes. Patients were assessed
      between days 7 and 12 post stroke. Diagnosis of apathy was made on the basis of
      clinical observation, interview and Apathy Scale. RESULTS: 13 out of 31 patients
      (42%) demonstrated apathy. Patients with apathy had lower NAA/Cr ratios in the
      right frontal lobe than non-apathetic subjects. The patient group was divided
      into two subgroups: Those with left hemisphere strokes, and those with right
      hemisphere strokes. Of these subjects, significantly lowered NAA/Cr ratios were
      found in the right hemispheres of apathetic patients in the subgroup with left
      sided brain lesions. CONCLUSIONS: These findings point to the association between
      apathy and frontal lobe integrity, suggest different reactions of the hemispheres
      and indicate that changes in the NAA/Cr ratio are related to the apathy.

PMID- 16084529
TI  - An analytical estimation of the energy cost for legged locomotion.
AB  - Legged locomotion requires the determination of a number of parameters such as
      stride period, stride length, order of leg movements, leg trajectory, etc. How
      are these parameters determined? It has been reported that the locomotor patterns
      of many legged animals exhibit common characteristics, which suggests that there
      exists a basic strategy for legged locomotion. In this study we derive an
      equation to estimate the cost of transport for legged locomotion and examine a
      criterion of the minimization of the transport cost as a candidate of the
      strategy. The obtained optimal locomotor pattern that minimizes the cost suitably
      represents many characteristics of the pattern observed in legged animals. This
      suggests that the locomotor pattern of legged animals is well optimized with
      regard to the energetic cost. The result also suggests that the existence of
      specific gait patterns and the phase transition between them could be the result
      due to optimization; they are induced by the change in the distribution of ground
      reaction forces for each leg during locomotion.

PMID- 16084530
TI  - A new method to model change in cutaneous blood flow due to mechanical skin
      irritation part II: parameter identification procedure.
AB  - Mechanical skin irritation, for example a light scratch with a needle, induces
      histamine and neuropeptide release on the line of stroke and in the surrounding
      tissue. Both histamine and neuropeptides are vasodilators. They cause
      vasodilation by changing the contraction state of the vascular smooth muscles and
      hence vessel compliance. Smooth muscle contraction state is very difficult to
      measure in vivo. For that reason we propose in this article an identification
      procedure to establish an irritation law. The law gives change in vessel
      compliance as a function of space, time and the intensity of the stroke. We have
      showed that vessel compliance increases immediately after the stroke not only on
      the line of stroke, but also in the surrounding tissue. Then, after a short
      delay, vessel compliance starts decreasing in the surrounding tissue, whereas
      vessel compliance on the line of stroke keeps increasing. Hence, blood is
      transported from the surrounding tissue to the line of stroke. In this way,
      higher blood volume on the line of stroke can be obtained than by only changing
      vessel compliance locally.

PMID- 16084531
TI  - Molecular mechanisms of action of angiopreventive anti-oxidants on endothelial
      cells: microarray gene expression analyses.
AB  - The anti-oxidants N-acetyl-l-cysteine (NAC) and (-)-epigallocatechin-3-gallate
      (EGCG) inhibit tumor vascularization by reducing endothelial cell migration and
      invasion in a similar, non additive and non synergistic manner but do not alter
      the growth of human umbilical vein endothelial cells. Here we address the effects
      of the two chemopreventive drugs on endothelial cell signaling by means of
      expression profiling and real-time PCR validation. We identify a series of
      angiogenesis related genes that are similarly regulated by the two drugs. Anti
      oxidant treated endothelial cells show gene expression profiles compatible with a
      less activated, less apoptosis prone and less migratory phenotype. The anti
      oxidants affect expression of several components of the TNFalpha response pathway
      including downstream genes that are regulated in the opposite direction in the
      absence of the inflammatory cytokine. The interference with the TNFalpha pathway
      is reflected by reduced NFkappaB activation in anti-oxidants treated cells but
      the compounds are not able to contrast TNFalpha mediated activation of NFkappaB.
      The chemopreventive action of these compounds thus relies on a reduction of basal
      levels of endothelial cell activation. Down-regulation of the TNFalpha responsive
      pro-metastatic, pro-inflammatory genes, urokinase plasminogen activator and
      selectin E, further implies anti-metastatic effects for these drugs.

PMID- 16084532
TI  - The role of human adult stem cells and cell-cell communication in cancer
      chemoprevention and chemotherapy strategies.
AB  - Since carcinogenesis is a multi-stage, multi-mechanism process, involving
      mutagenic, cell death and epigenetic mechanisms, during the
      "initiation/promotion/and progression" phases, chemoprevention must be based on
      understanding the underlying mechanism(s) of each phase, In principle, prevention
      of each of these phases could reduce the risk to cancer. However, because
      reducing the mutagenic/initiation phase to a zero level is impossible, the most
      efficacious intervention would be at the promotion phase that requires a
      sustained exposure to promoting conditions/agents. In addition, assuming the
      "target" cells for carcinogenesis are the pluri-potent stem cells and their early
      progenitor or transit cells, chemoprevention strategies for inhibiting the
      promotion of these two types of pre-malignant "initiated" cells will require
      different kinds of agents. A hypothesis will be proposed that involves adult stem
      cells, which express Oct-4 gene and lack gap junctional intercellular
      communication (GJIC-) or the early progenitor cells which express GJIC+ and are
      partially-differentiated, if initiated, will be promoted by agents that either
      inhibit secreted negative growth regulators or by inhibitors of GJIC.
      Consequently, anti-tumor promoting chemopreventing agents to each of these two
      types of initiated cells must have different mechanisms of action and work on
      different target cells. Assuming stem cells are target cells for carcinogenesis,
      an alternative method of chemoprevention would be to reduce the stem cell pool.
      Many classes of anti-tumor promoter chemopreventive agents, such as green tea
      components, resveratrol, caffeic acid phenethylene ester, either up-regulate GJIC
      in stem cells or prevent the down regulation of GJIC by tumor promoters in early
      progenitor cells.

PMID- 16084533
TI  - Advanced glycoxidation end products in chronic diseases-clinical chemistry and
      genetic background.
AB  - Several diseases (atherosclerosis, diabetes mellitus, chronic renal failure) are
      associated with oxidative and carbonyl stress, microinflammation and eventually
      autoimmune reaction. Both oxidative and carbonyl stress cause damage to important
      biological structures-proteins, carbohydrates, lipids and nucleic acids and may
      enhance inflammatory response. New compounds and modified structures are formed,
      among them advanced oxidation protein products (AOPP), advanced glycation end
      products (AGEs-e.g. pentosidine, carboxymethyllysine) and advanced
      lipoperoxidation end products (ALEs). Accumulation of glycoxidation products,
      upregulation of protective mechanisms like glyoxalase I as well as enhanced
      transcription of genes coding for cytokines, growth factors and adhesive
      molecules via AGE-RAGE (receptor for AGEs) interaction and subsequent increase of
      classical acute phase reactants (e.g. CRP-C-reactive protein or orosomucoid) can
      be observed in a variety of chronic diseases. Additionally, several RAGE gene
      polymorphisms have shown association with some pathological states-diabetic
      complications, vascular damage, inflammatory response or antioxidant status.
      Recent advances in understanding the pathogenesis of chronic diseases provide new
      possibilities for diagnostics and monitoring of severely ill patients, however,
      further studies are still required to establish efficient therapeutical
      strategies.

PMID- 16084534
TI  - Ionizing radiation and genetic risks XIV. Potential research directions in the
      post-genome era based on knowledge of repair of radiation-induced DNA double
      strand breaks in mammalian somatic cells and the origin of deletions associated
      with human genomic disorders.
AB  - Recent estimates of genetic risks from exposure of human populations to ionizing
      radiation are those presented in the 2001 report of the United Nations Scientific
      Committee on the Effects of Atomic Radiation (UNSCEAR). These estimates
      incorporate two important concepts, namely, the following: (1) most radiation
      induced mutations are DNA deletions, often encompassing multiple genes, but only
      a small proportion of the induced deletions is compatible with offspring
      viability; and (2) the viability-compatible deletions induced in germ cells are
      more likely to manifest themselves as multi-system developmental anomalies rather
      than as single gene disorders. This paper: (a) pursues these concepts further in
      the light of knowledge of mechanisms of origin of deletions and other
      rearrangements from two fields of contemporary research: repair of radiation
      induced DNA double-strand breaks (DSBs) in mammalian somatic cells and human
      molecular genetics; and (b) extends them to deletions induced in the germ cell
      stages of importance for radiation risk estimation, namely, stem cell
      spermatogonia in males and oocytes in females. DSB repair studies in somatic
      cells have elucidated the roles of two mechanistically distinct pathways, namely,
      homologous recombination repair (HRR) that utilizes extensive sequence homology
      and non-homologous end-joining (NHEJ) that requires little or no homology at the
      junctions. A third process, single-strand annealing (SSA), which utilizes short
      direct repeat sequences, is considered a variant of HRR. HRR is most efficient in
      late S and G2 phases of the cell cycle and is a high fidelity mechanism. NHEJ
      operates in all cell cycle phases, but is especially important in G1. In the
      context of radiation-induced DSBs, NHEJ is error-prone. SSA is also an error
      prone mechanism and its role is presumably similar to that of HRR. Studies in
      human molecular genetics have demonstrated that the occurrence of large
      deletions, duplications or other rearrangements in certain regions of the genome
      is related to the presence of large segments of repetitive DNA called segmental
      duplications (also called duplicons or low copy repeats, LCRs) in such regions.
      The mechanism that is envisaged for the origin of deletions and other
      rearrangements involves misalignment of region-specific LCRs of homologous
      chromosomes in meiosis followed by unequal crossing-over (i.e., non-allelic
      homologous recombination, NAHR). We hypothesize that: (a) in spermatogonial stem
      cells, NHEJ is probably the principal mechanism underlying the origin of
      radiation-induced deletions, although SSA and NAHR may also be involved to some
      extent, especially at low doses; and (b) in irradiated oocytes, NAHR is likely to
      be the main mechanism for generating deletions. We suggest future research
      possibilities, including the development of models for identifying regions of the
      genome that are susceptible to radiation-induced deletions. Such efforts may have
      particular significance in the context of the estimation of genetic risks of
      radiation exposure of human females, a problem that is still with us.

PMID- 16084535
TI  - Effect of genetic polymorphisms of MnSOD and MPO on the relationship between PAH
      exposure and oxidative DNA damage.
AB  - To investigate the effect of genetic polymorphisms on the oxidative damage caused
      by PAH exposure, we measured urinary 1-hydroxypyrene (1-OHP) and 8
      hydroxydeoxyguanosine (8-OHdG) levels to determine exposure and oxidative injury
      in university students. After examining myeloperoxidase (MPO) and manganese
      superoxide dismutase (MnSOD) genotypes by PCR and RFLP, we evaluated the effects
      of these polymorphisms on the relationship between the urinary levels of 1-OHP
      and 8-OHdG. No significant relation was observed between log 1-OHP and 8-OHdG
      concentrations in the whole study group (p=0.182), or between urinary 8-OHdG
      levels and polymorphisms of MnSOD or MPO (p=0.539 and 0.993, respectively).
      However, significant differences of regression coefficient were found for the
      relation between urinary log 1-OHP and urinary 8-OHdG concentrations in the
      presence of different MnSOD or MPO genotypes by multiple regression after
      controlling for age, sex, body mass index, cotinine, and smoking. In those with
      the MnSOD Val/Ala or Ala/Ala genotypes this regression coefficient was 1.480
      (p=0.040), whereas for the MnSOD Val/Val genotype it was 0.088 (p=0.859). The
      higher regression coefficient was obtained for the subject group with the MnSOD
      Val/Ala or Ala/Ala genotype in combination with the MPO G/G genotype (p=0.012).
      We suggest that the oxidative injury caused by PAH exposure is modulated by
      genetic polymorphisms such as MnSOD and MPO.

PMID- 16084536
TI  - Maternal deprivation in neonatal rats alters the expression of circadian system
      under light-dark cycles and restricted daily feeding in adulthood.
AB  - Effects of maternal deprivation (MD) with different conditions were examined on
      the circadian rhythms in plasma corticosterone and locomotor activity in adult
      rats under ad libitum and restricted daily feeding (RF), in which rats had free
      access to food for 2 h for 3 weeks. Three different types of MD were performed
      from postnatal day 1 (P1) to day 6 (P6); MD for 12 h/day (MD12), for 3 h/day in
      the morning (MD3am) and in the afternoon (MD3pm). Under ad libitum feeding,
      corticosterone levels at 08:00 h and 24:00 h were significantly increased in MD12
      rats. A similar increase was detected in MD3am rats, but not in MD3pm rats. Under
      the RF, corticosterone levels at 08:00 h, 24:00 h, and 04:00 h were significantly
      increased in MD12 rats. Similar elevations were detected in MD3am rats, but not
      in MD3pm rats. Furthermore, prefeeding locomotor activities under the RF
      increased significantly in MD12 rats. A similar increase was observed in MD3am
      rats, but not in MD3pm rats. Keeping ambient temperature and humidity at 37
      degrees C and 70-80% during MD attenuated the effects of MD on the corticosterone
      rhythmicities under RF as well as ad lib feeding. It is concluded that MD in the
      early postnatal period influences the expressions of circadian rhythms in plasma
      corticosterone and locomotor activity in adult rats. Not only the length but also
      the time of day of MD seems to be critical for these effects. Ambient temperature
      and/or humidity are suggested to be one of the factors by which MD exerts its
      effect.

PMID- 16084537
TI  - Ferula hermonis impairs sexual behavior in hormone-primed female rats.
AB  - The influence of Ferula hermonis root extract on sexual behavior was studied in
      female rats. Sexual receptivity, proceptivity and paced mating behavior were
      evaluated in ovariectomized females primed with estradiol benzoate (EB) and
      progesterone (P) and then treated with F. hermonis extract acutely (30 and 60
      mg/kg) or subchronically (1 and 10 mg/kg daily for 10 consecutive days). A
      significant reduction in lordosis responses was observed in rats after acute (60
      mg/kg) or subchronic (1 and 10 mg/kg) administration of the plant extract.
      Similarly, a decrease in proceptive behaviors was exhibited by F. hermonis
      treated rats in comparison with EB+P controls. No difference was found in the
      patterns of paced mating behavior between control and treated animals. The
      present results demonstrate that the acute or repeated ingestion of F. hermonis
      specifically impairs the receptive and proceptive components of female sexual
      behavior. The effect could be the consequence of an antiestrogenic action of the
      extract in hormone-primed female rats.

PMID- 16084538
TI  - HZE radiation and dopaminergic modification of startle and prepulse inhibition in
      mice.
AB  - C57BL/6 mice were exposed to 5 Gy (28)Si or (56)Fe particle radiation in order to
      explore the immediate or short-latency effect of exposure to high energy (HZE)
      particle radiation on dopaminergic modification of acoustic startle and prepulse
      inhibition. The radiation is representative of the type which would be
      encountered as galactic cosmic rays during long-duration space flight. The
      acoustic startle response was elicited with 120 dB white noise and prepulse
      inhibition of the startle response was produced with 79 dB and 86 dB stimuli
      presented with a 125 ms onset asynchrony. Startle reactivity was inhibited by
      (56)Fe radiation but not by (28)Si particles. Apomorphine (3 mg/kg) produced a
      general inhibition of startle reactivity while haloperidol (1 mg/kg) facilitated
      it. Apomorphine disrupted prepulse inhibition, but only in animals which were not
      exposed to radiation. Both (56)Fe and (28)Si radiation exposure attenuated the
      disruption of prepulse inhibition induced by apomorphine. In contrast, the
      facilitation of prepulse inhibition induced by haloperidol was not modified by
      radiation. These data are consistent with a short-latency disruption of
      dopaminergic systems by HZE particle radiation. We speculate that this disruption
      may occur as a restriction in the capacity of the dopaminergic system.

PMID- 16084539
TI  - Phragmalin-type limonoids from the mangrove plant Xylocarpus granatum.
AB  - Five new phragmalin-type limonoids, xyloccensins Q-U (1-5), along with
      xyloccensin P were isolated from the stem bark of the mangrove plant Xylocarpus
      granatum. Their structures were elucidated on the basis of extensive 1D and 2D
      NMR as well as IR and MS spectroscopic data analyses.

PMID- 16084540
TI  - An evaluation of the impact of a national health demonstration project on testing
      and management for Chlamydia trachomatis infections in two regions of Scotland.
AB  - OBJECTIVES: To compare clinical practice relating to testing for, and management
      of, genital Chlamydia trachomatis infection in the Lothian and Grampian regions
      of Scotland as part of an evaluation of a Government-funded health demonstration
      project in Lothian, Healthy Respect. STUDY DESIGN: Clinical audit against
      standards developed from a national clinical guideline. METHODS: Clinical
      practice relating to testing for, and management of, genital C. trachomatis
      infection was assessed against standards for good quality care developed from a
      national clinical guideline (Scottish Intercollegiate Guidelines Network
      Guideline 42). Audit methods comprised: postal survey of primary care clinicians;
      review of referral letters from primary to secondary care; and review of primary
      and secondary care patient case records. Findings from Lothian and Grampian were
      compared. RESULTS: Questionnaires were returned by 167 primary care clinicians in
      Lothian and 96 in Grampian. Clinicians in Lothian and Grampian gave similar
      responses relating to: testing of symptomatic patients (87 vs 88%); offer of
      testing for asymptomatic young patients (55 vs 55%); choice of antichlamydial
      agent (47 vs 42% azithromycin as first line); and follow-up strategies (50 vs 51%
      offer follow-up in primary care). Clinicians in Lothian were significantly more
      likely to participate in partner notification work (57 vs 44%; P=0.04) and to
      agree with statements reflecting 'perceived self-efficacy' in chlamydia-related
      care (57 vs 48%; P=0.006). Referral letters from primary to secondary care were
      reviewed for 31 women with genital symptoms in Lothian and 28 in Grampian. More
      women in Lothian were tested for chlamydia prior to referral (65 vs 39%;
      difference not significant). Review of primary care records for consultations in
      young people (145 in Lothian; 203 in Grampian) showed a higher level of chlamydia
      testing in Grampian (Lothian, 14%; Grampian, 34%; P<0.0001). However, review of
      secondary care records (n=39) showed a much higher level of testing in Lothian
      (Lothian, 75%; Grampian, 9%; P<0.0001). Review of secondary care records relating
      to proven chlamydia-positive women (n=159) suggested better care in Lothian in
      relation to ensuring antibiotic treatment (Lothian, 91%; Grampian, 74%; P=0.004),
      and use of the preferred antibiotic, azithromycin (Lothian, 78%; Grampian, 37%;
      P<0.0001). However, documented referral to a health adviser appeared to be better
      in Grampian (Lothian, 32%; Grampian, 48%; P=0.048). CONCLUSIONS: During the
      period of activity of the Healthy Respect demonstration project, few differences
      were detected between clinicians in Lothian and Grampian with regard to chlamydia
      related practice. In both regions, clinicians appeared to be very aware of the
      need to test for chlamydia in patients with relevant symptoms, but were less
      likely to offer opportunistic testing to young patients without specific
      symptoms. These findings suggest that Healthy Respect in Lothian has had little
      impact on clinicians. However, these findings must be considered within the
      context of a broader evaluation, and it is noteworthy that the few significant
      differences that were detected tended to suggest better practice in Lothian.

PMID- 16084541
TI  - Increased incidence of latex allergy in children with allergic diseases in Japan.
AB  - The incidence of latex allergy is increasing in Japanese adults. However, the
      changing incidence of latex allergy in children with or without allergic diseases
      has not been reported in detail. After obtaining written informed consent from
      parents, Japanese children under 14 years of age were studied. In total, 776 non
      atopic children, 802 children with allergic rhinitis (AR), 706 children with
      bronchial asthma (BA) and 844 children with atopic eczema/dermatitis syndrome
      (AEDS) were asked about symptoms of latex allergy, and tested by serum latex
      specific IgE, skin prick test to latex allergen and latex-glove-wearing test
      between 2001 and 2003. All the patients were outpatients at Ujitakeda Hospital,
      while the non-atopic children were children of the staff of Ujitakeda Hospital or
      Unitika Ltd. This was a retrospective study. The incidence of latex allergy in
      2001/2002/2003 was 1.4/3.1/4.7% in non-atopic children, 3.1/5.1/9.1% in AR
      patients, 3.6/6.5/10.3% in BA patients and 6.1/11.3/15.9% in AEDS patients,
      respectively. Moreover, although no cases of anaphylactic shock were noted in
      allergic patients in 2001, two and eight cases were noted in 2002 and 2003,
      respectively. These results indicate that the incidence of latex allergy is
      increasing in paediatric patients with allergic diseases. A latex-reduced
      environment may be desirable in future.

PMID- 16084542
TI  - Assessing intervention effects in a community-based trial to reduce self-harm: a
      methodological case study.
AB  - This paper considers the assessment of the impact of a community-based randomized
      controlled trial to reduce repeat deliberate self-harm. It considers the
      drawbacks in simplistic applications of conventional significance testing
      procedures, as well as possible failures regarding the statistical assumptions
      underlying such tests. Instead, the paper considers how relevant prior
      information might be incorporated within a fully Bayesian-model-based assessment
      procedure. The model includes a latent trait approach to patient morbidity;
      controlling for morbidity and other patient characteristics enhances the impact
      of the intervention (measured by a hazard rate ratio). If allowance is made for
      external information (e.g. ethical approval of the treatment), the weight of
      evidence shifts towards a positive intervention effect.

PMID- 16084543
TI  - The potential of public health to enhance chronic disease management.

PMID- 16084544
TI  - Prevention practices and cancer screening among general practitioners in Picardy,
      France.
AB  - BACKGROUND: Due to their frequent contact with a large proportion of the
      population, general practitioners (GPs) appear to play a particularly important
      role in primary and secondary (screening) cancer prevention. The objective of
      this survey was to describe the attitudes of GPs in relation to the major risk
      factors of cancer, and the most frequent forms of cancer screening. METHODS: A
      questionnaire concerning primary prevention and cancer screening by GPs was sent
      to all doctors in the Picardy region. In total, 480 GPs agreed to participate in
      this survey (31%). The questions concerned primary prevention (alcohol, smoking,
      diet, sun exposure, etc.) and cancer screening (breast, cervix, colorectal,
      prostate and other cancers). GPs were also questioned about their perception of
      these preventive actions and the difficulties that they encounter in application
      of these measures. RESULTS: The most structured preventive action appears to
      concern smoking in terms of primary prevention. GPs report greater difficulties
      in the prevention of alcoholism or dietary advice. A marked diversity of clinical
      practice was also observed in terms of cancer screening, even for cancers for
      which clear guidelines have been defined, such as breast, cervical and colorectal
      cancer. CONCLUSION: GPs appear to be receptive to cancer prevention, but
      encounter many difficulties in daily application due to lack of time or poor
      patient compliance.

PMID- 16084545
TI  - Geospatial analysis of hepatitis C in Connecticut: a novel application of a
      public health tool.
AB  - OBJECTIVES: This study aimed to use geographic information systems (GIS) that
      facilitate analysis of associations between location, environment and disease to
      document the non-random distribution of hepatitis C, identify infection cluster
      areas, and describe the demographic characteristics of those areas. METHODS:
      Spatial analysis was conducted of newly reported positive hepatitis C test
      results using the Connecticut Hepatitis C Reporting Database. A complete database
      of unduplicated hepatitis C laboratory reports that were sent to the Connecticut
      Department of Public Health during 1999 was created. Spatial filtering was used
      to eliminate random noise generated by sparsely populated towns or small number
      of cases per town. Cluster analysis was used to determine whether cases of
      hepatitis C virus (HCV) infection tend to occur closer in space to other cases
      than would be expected by chance alone. The demographic attributes of identified
      clusters of HCV-positive reports were examined. RESULTS: Areas with the highest
      concentration of HCV reports roughly correspond to the major metropolitan areas
      of Connecticut. Six significant clusters of HCV reports were identified in
      Connecticut. Four of the six clusters identified were located in the most densely
      populated and most urban areas of the state. All but one identified cluster had
      been described previously as areas of substantial injection drug use, as
      indicated by their designation as five of the sites of syringe exchange
      programmes in Connecticut. This finding suggests that geospatial analysis may
      assist in the identification of clusters that would not otherwise be suspected
      based on local demographics or other characteristics. CONCLUSIONS: These findings
      contribute significantly to the understanding of the state-specific epidemiology
      of HCV infection. This methodology can be applied wherever a similar database
      exists to enable the implementation of targeted prevention and educational
      campaigns to raise awareness of HCV risk factors, the importance of being tested,
      and treatment options.

PMID- 16084546
TI  - Plasma malonaldehyde (MDA) and total antioxidant status (TAS) during lactation in
      dairy cows.
AB  - Metabolic profiles are widely used to monitor health, reproductive status and
      nutritional status. In the last few years, the evaluation of oxidative stress has
      contributed increasingly to our knowledge of the fundamental mechanisms involved
      in metabolic disorders, especially important in dairy cows, in which lactation
      imposes great physiological demands on the body's homeostatic mechanisms. The aim
      of the present study was to evaluate oxidative status in healthy cows during
      lactation (from lactation onset to peak lactation) using two parameters: (i)
      plasma levels of malondialdehyde (MDA) and (ii) total antioxidant status (TAS).
      Our results confirm that nutrition can influence the characteristic metabolic
      changes occurring between lactation onset and peak lactation. In addition, the
      combination of MDA and TAS can provide complementary information about the
      metabolic status of the cow. Thus, the proper metabolic adaptation to the onset
      of lactation, showed by metabolic profiles, contrasts with the high levels of
      free radicals which cause lipid peroxidation and high MDA values (68.99+/-33.64
      microm/L) which is maintained only for a short period of time. In this moment,
      the antioxidant system can cope efficiently with lipoperoxide production. The
      most remarkable fact was the great inter-individual variations observed in MDA
      that might be studied in further investigations. When the animal reaches peak
      lactation, metabolic status is stabilized, and this is reflected by antioxidant
      status with mean values of 28.87+/-5.33 microm/L for MDA and 0.154+/-0.002 mmol/L
      for TAS values.

PMID- 16084547
TI  - Phase I safety study of Praneem polyherbal vaginal tablet use among HIV
      uninfected women in Pune, India.
AB  - Praneem polyherbal formulations containing purified extracts of Azadirachta
      indica (neem tree) have shown activity against HIV and sexually transmitted
      disease pathogens in studies in vitro. The product also has contraceptive
      properties. This has prompted its development as a possible microbicide. We
      evaluated the safety of Praneem polyherbal tablet use among HIV-uninfected women.
      Twenty eligible women were enrolled in a Phase I open-label study requiring 14
      days of consecutive intravaginal use of Praneem polyherbal tablets. Nine (45%)
      participants experienced 17 episodes of genital irritation. Transient genital
      itching was reported by eight (40%) participants, burning micturation by two
      (10%) and lower abdominal pain, genital burning and intermenstrual spotting by
      one (5%) each. On colposcopy, petechial haemorrhage was observed in two
      participants, one on day 7 and the other on day 14, and both were resolved
      without any treatment. There were no serious adverse events. Praneem polyherbal
      tablets were found to be safe for once daily intravaginal use for 14 consecutive
      days in sexually active HIV-uninfected women and a Phase II study may be taken up
      as a priority.

PMID- 16084548
TI  - Quinine for the treatment of uncomplicated Plasmodium falciparum malaria in
      eastern Sudan.
AB  - An observational clinical trial was conducted in New Halfa, eastern Sudan, in
      November and December 2003. Sixty-two patients with uncomplicated Plasmodium
      falciparum malaria were treated with oral quinine (10 mg/kg thrice daily for 7
      d); 47 (76%) of these patients were followed-up to day 28, and 5 (10.6%) of them
      appeared to have late treatment failures. The parasitological failures were early
      R1 in two (4.3%) patients and late R1 in three (6.4%) patients. The reappearance
      of parasites in three of these five patients were true recrudescences rather than
      a re-infection, based on genetic evidence. The present results and those of
      earlier investigations indicate that the response to quinine in this area may be
      faltering.

PMID- 16084549
TI  - Activations of c-fos/c-jun signaling are involved in the modulation of
      hypothalamic superoxide dismutase (SOD) and neuropeptide Y (NPY) gene expression
      in amphetamine-mediated appetite suppression.
AB  - Amphetamine (AMPH) is known as an anorectic agent. The mechanism underlying the
      anorectic action of AMPH has been attributed to its inhibitory action on
      hypothalamic neuropeptide Y (NPY), an appetite stimulant in the brain. This study
      was aimed to examine the molecular mechanisms behind the anorectic effect of
      AMPH. Results showed that AMPH treatment decreased food intake, which was
      correlated with changes of NPY mRNA level, but increased c-fos, c-jun and
      superoxide dismutase (SOD) mRNA levels in hypothalamus. To determine if c-fos or
      c-jun was involved in the anorectic response of AMPH, infusions of antisense
      oligonucleotide into the brain were performed at 1 h before daily AMPH treatment
      in freely moving rats, and the results showed that c-fos or c-jun knockdown could
      block this anorectic response and restore NPY mRNA level. Moreover, c-fos or c
      jun knockdown could partially block SOD mRNA level that might involve in the
      modulation of NPY gene expression. It was suggested that c-fos/c-jun signaling
      might involve in the central regulation of AMPH-mediated feeding suppression via
      the modulation of NPY gene expression.

PMID- 16084550
TI  - Isolation and characterization of two disintegrins inhibiting ADP-induced human
      platelet aggregation from the venom of Crotalus scutulatus scutulatus (Mohave
      Rattlesnake).
AB  - Disintegrins and disintegrin-like proteins are molecules found in the venom of
      four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The
      disintegrins are nonenzymatic proteins that inhibit cell-cell interactions, cell
      matrix interactions, and signal transduction, and may have potential in the
      treatment of strokes, heart attacks, cancers, and osteoporosis. Prior to 1983,
      the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake) was known to be
      only neurotoxic; however, now there is evidence that these snakes can contain
      venom with: (1) neurotoxins; (2) hemorrhagins; and (3) both neurotoxins and
      hemorrhagins. In this study, two disintegrins, mojastin 1 and mojastin 2, from
      the venom of a Mohave rattlesnake collected in central Arizona (Pinal County),
      were isolated and characterized. The disintegrins in these venoms were identified
      by mass-analyzed laser desorption ionization/time-of-flight/time-of-flight
      (MALDI/TOF/TOF) mass spectrometry as having masses of 7.436 and 7.636 kDa. Their
      amino acid sequences are similar to crotratroxin, a disintegrin isolated from the
      venom of the western diamondback rattlesnake (C. atrox). The amino acid sequence
      of mojastin 1 was identical to the amino acid sequence of a disintegrin isolated
      from the venom of the Timber rattlesnake (C. horridus). The disintegrins from the
      Mohave rattlesnake venom were able to inhibit ADP-induced platelet aggregation in
      whole human blood both having IC50s of 13.8 nM, but were not effective in
      inhibiting the binding of human urinary bladder carcinoma cells (T24) to
      fibronectin.

PMID- 16084551
TI  - 2-Amino-14,16-dimethyloctadecan-3-ol, a new sphingosine analogue toxin in the
      fungal genus Fusarium.
AB  - 2-Amino-14,16-dimethyloctadecan-3-ol (2-AOD-3-ol) was isolated from the cytotoxic
      rice culture extract of a strain of Fusarium avenaceum, which had previously been
      isolated from Norwegian grain. The structural information was obtained from LC
      MS/MS, GC-MS, NMR spectroscopy and high-resolution MS data. The metabolite has a
      striking similarity to sphinganine, an intermediate in the biosynthesis of the
      sphingolipids. This similarity is a major feature of the so-called sphingosine
      analogue toxins; the most studied being the AAL toxins and the fumonisins. 2-AOD
      3-ol was found to be cytotoxic to the rat hepatoma cell line H4IIE-W and to the
      porcine epithelial kidney cell line PK(15) at concentrations (EC(50)) of 16 and
      24 microM, respectively. The metabolite has been found in F. avenaceum inoculated
      wheat that was treated to support ideal conditions for Fusarium growth,
      demonstrating that the fungus has the potential to produce the metabolite under
      field conditions, which may occur in Northern Europe.

PMID- 16084552
TI  - In vivo studies on toxin accumulation in liver and ultrastructural changes of
      hepatocytes of the phytoplanktivorous bighead carp i.p.-injected with extracted
      microcystins.
AB  - Phytoplanktivorous bighead carp were injected i.p. with extracted microcystins
      (mainly MC-RR and -LR) at two doses, 200 and 500 MC-LReq.microg kg(-1) bw, and
      the changes in extractable MCs in liver and in the ultrastructure of hepatocytes
      were studied at 1, 3, 12, 24 and 48 h after injection. Quantitative and
      qualitative determinations of MCs in the liver were conducted by HPLC and LC-MS,
      respectively. MC concentration in the liver reached the maxima at 12h (2.89
      microg MCsg(-1) dry weight at the lower dose) or at 3h (5.43 microg MCsg(-1) dry
      weight at the higher dose) post-injection, followed by sharp declines afterwards,
      whereas the ultrastructural changes of hepatocytes in both dose groups suggest
      progressive increases in severity toward the directions of apoptosis and necrosis
      from 1 to 24h, respectively. There were two new findings in fish: widening of
      intercellular spaces was among the early ultrastructural changes induced by MCs
      and ultrastructural recovery of hepatocytes was evident at 48 h post-injection in
      both dose groups. Both the present and previous studies suggest that with in vivo
      or in vitro exposure to microcystins, hepatocyte damage in fish tends to proceed
      toward the direction of apoptosis at lower MC concentrations but toward the
      direction of necrosis at high MC concentrations. The temporal dynamics of MCs in
      the liver suggest that bighead carp may have a mechanism to degrade or bind MC-LR
      actively after it enters the blood system.

PMID- 16084553
TI  - Microcystin-RR-induced accumulation of reactive oxygen species and alteration of
      antioxidant systems in tobacco BY-2 cells.
AB  - Microcystins are cyclic heptapeptide hepatoxins produced by cyanobacteria. It has
      been shown that microcystins have adverse effects on animals and on plants as
      well. Previous researches also indicated that microcystins were capable of
      inducing oxidative damage in animals both in vivo and in vitro. In this study,
      tobacco BY-2 suspension cell line was applied to examine the effects of
      microcystin-RR on plant cells. Cell viability and five biochemical parameters
      including reactive oxygen species (ROS), superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxide (GPX) and peroxide dismutase (POD) were investigated
      when cells were exposed to 50mg/L microcystin-RR. Results showed that microcystin
      RR evoked decline of the cell viability to approximately 80% after treating for
      144 h. ROS levels, POD and GPX activities of the treated cells were gradually
      increased with a time dependent manner. Changes of SOD and CAT activities were
      also detected in BY-2 cells. After 168 h recovery, ROS contents, POD, GPX and CAT
      activities returned to normal levels. These results suggest that the microcystin
      RR can cause the increase of ROS contents in plant cells and these changes led to
      oxidant stress, at the same time, the plant cells would improve their antioxidant
      abilities to combat mirocystin-RR induced oxidative injury.

PMID- 16084554
TI  - Protective efficacy in chickens, geese and ducks of an H5N1-inactivated vaccine
      developed by reverse genetics.
AB  - We generated a high-growth H5N1/PR8 virus by plasmid-based reverse genetics. The
      virulence associated multiple basic amino acids of the HA gene were removed, and
      the resulting virus is attenuated for chickens and chicken eggs. A formalin
      inactivated oil-emulsion vaccine was prepared from this virus. When SPF chickens
      were inoculated with 0.3 ml of the vaccine, the hemagglutinin-inhibition (HI)
      antibody became detectable at 1 week post-vaccination (p.v.) and reached a peak
      of 10log2 at 6 weeks p.v. then slowly declined to 4log2 at 43 weeks p.v.
      Challenge studies performed at 2, 3 and 43 weeks p.v. indicated that all of the
      chickens were completely protected from disease signs and death. Ducks and geese
      were completely protected from highly pathogenic H5N1 virus challenge 3 weeks
      p.v. The duration of protective immunity in ducks and geese was investigated by
      detecting the HI antibody of the field vaccinated birds, and the results
      indicated that 3 doses of the vaccine inoculation in geese could induce a 34
      weeks protection, while 2 doses induced more than 52 weeks protection in ducks.
      We first reported that an oil-emulsion inactivated vaccine derived from a high
      growth H5N1 vaccine induced approximately 10 months of protective immunity in
      chickens and demonstrated that the oil-emulsion inactivated avian influenza
      vaccine is immunogenic for geese and ducks. These results provide useful
      information for the application of vaccines to the control of H5N1 avian
      influenza in poultry, including chickens and domestic waterfowl.

PMID- 16084555
TI  - The generation of recombinant influenza A viruses expressing a PB2 fusion protein
      requires the conservation of a packaging signal overlapping the coding and
      noncoding regions at the 5' end of the PB2 segment.
AB  - We generated recombinant A/WSN/33 influenza A viruses expressing a PB2 protein
      fused to a Flag epitope at the N- (Flag-PB2) or C-terminus (PB2-Flag), which
      replicated efficiently and proved to be stable upon serial passage in vitro on
      MDCK cells. Rescue of PB2-Flag viruses required that the 5' end of the PB2
      segment was kept identical to the wild-type beyond the 34 noncoding terminal
      nucleotides. This feature was achieved by a duplication of the 109 last
      nucleotides encoding PB2 between the Flag sequence and the 5'NCR. In PB2 mini
      genomes rescue experiments, both the 5' and 3' coding ends of the PB2 segment
      were found to promote the incorporation of mini-genomes into virions. However,
      the presence of the Flag sequence at the junction between the 3'NCR and the
      coding sequence did not prevent the rescue of Flag-PB2 viruses. Our observations
      define requirements that may be useful for the purpose of engineering influenza
      RNAs.

PMID- 16084556
TI  - Optic-flow and egocentric-direction strategies in walking: central vs peripheral
      visual field.
AB  - The impact of a central or peripheral visual field loss on the vision strategy
      used to guide walking was determined by measuring walking paths of visually
      impaired participants. An immersive virtual environment was used to dissociate
      the expected paths of the optic-flow and egocentric-direction strategies by
      offsetting the walker's point of view from the actual direction of walking.
      Environments consisted of a goal within a forest, the goal alone, or the forest
      alone following a brief presentation of the goal. The first two environments
      allowed an evaluation of the visual information used in a goal-directed task
      whereas the third environment investigated the information used in a memory
      guided task. Participants had either a central (CFL) or peripheral visual field
      loss (PFL) or were fully sighted (FS). Results showed that, for the goal-directed
      task, the CFL group was less influenced by optic flow than was an age-matched FS
      group. Optic flow decreased heading error by only 1.3 degrees (16%) in the CFL
      group compared to 3.6 degrees (42%) in the FS group. The PFL group showed an
      optic-flow influence (2.4 degrees or 26%) comparable to an older, age-matched FS
      group (2.9 degrees or 31%). For the memory-guided task, all but the PFL group had
      heading errors comparable to those obtained in the goal-alone scene,
      demonstrating the ability to use an egocentric-direction strategy with a stored
      representation of either the goal's position or an offset relative to a landmark
      instead of a visible goal. The paths of the PFL group veered significantly from
      the predicted paths of both the optic-flow and egocentric-direction strategies.
      The findings of this study suggest that central vision is important for using
      optic flow to guide walking, whereas peripheral vision is important for
      establishing and/or updating an accurate representation of spatial structure for
      navigation.

PMID- 16084557
TI  - Effect of NOM, turbidity and floc size on the PAC adsorption of MIB during alum
      coagulation.
AB  - The effect of natural organic material (NOM) and turbidity on the powdered
      activated carbon (PAC) adsorption of the odour compound 2-methylisoborneol (MIB)
      was evaluated during alum coagulation. The character of the flocs, in terms of
      their size and fractal dimensions (Df), was used to interpret the observed
      adsorption behaviour of MIB during the coagulation process. As the alum dose was
      increased, the adsorption of MIB decreased. This was determined to be due to the
      size of the flocs, with larger flocs incorporating PAC into their structure,
      reducing the efficiency of mixing, and the bulk diffusion kinetics for the MIB
      molecule. The presence of turbidity also reduced MIB adsorption due to the
      formation of larger flocs. The character of NOM was found to have a greater
      influence on the adsorption of MIB than the floc structure.

PMID- 16084558
TI  - Adsorption of molybdate and tetrathiomolybdate onto pyrite and goethite: effect
      of pH and competitive anions.
AB  - The adsorption of two major molybdenum (Mo) species, molybdate (MoO4(2-)) and
      tetrathiomolybdate (MoS4(2-)) onto two main iron minerals pyrite (FeS2) and
      goethite (FeOOH) is addressed to elucidate the possible mechanisms of molybdenum
      immobilization in anoxic sediments. Suspensions of MoS4(2-) (or MoO4(2-)) and
      goethite (or pyrite) in 0.1M NaCl solution were equilibrated under anoxic
      conditions at 25 degrees C in the pH range from 3 to 10. The competitive effects
      of sulfate, phosphate, and silicate on the adsorption of MoO4(2-) and MoS4(2-) by
      pyrite and goethite are also addressed. Adsorption of MoO4(2-) and MoS4(2-) on
      pyrite and goethite is in general well described by a Langmuir model at low pH;
      the extent of sorption is a function of pH and the surface loading. Maximum
      sorption is observed in the acidic pH range (pH<5) at low surface loading. The
      adsorption of molybdenum (micromol g(-1)) depends upon Mo species and on the type
      of iron mineral following the order: MoS4(2-)-goethite > MoO4(2-)-goethite >
      MoS4(2-)-pyrite > MoO4(2-)-pyrite. Phosphate appears to compete strongly with
      MoO4(2-) and MoS4(2-) for the sorption sites of pyrite and goethite. The strength
      of the phosphate competitive effect follows the sequence of MoO4(2-)-goethite
      approximately = MoO4(2-)-pyrite > MoS4(2-)-pyrite > MoS4(2-)-goethite. Silicate
      and sulfate have a negligible effect on the sorption of MoO4(2-) and MoS4(2-).
      The preferred adsorption by iron mineral of MoS4(2-), as well as its behavior in
      the presence of competitive anions suggests that tetrathiomolybdate species may
      be an ultimate reservoir and may control Mo enrichment in the sediments.

PMID- 16084559
TI  - Coadsorption of carbofuran and lead at the air/water interface. Possible
      occurrence of non-volatile pollutant cotransfer to the atmosphere.
AB  - The weak solubility of carbofuran allows adsorption at the air/water interface.
      Carbofuran-rich layers can then induce the coadsorption of metallic salts such as
      lead nitrate; on the other hand, when carbofuran is missing, no adsorption of
      this salt takes place. This phenomenon was quantitatively studied through surface
      tension measurements under concentration conditions close to the environmental
      ones. Heavy metal salt adsorbed about ten times more than carbofuran. Evidence
      was then provided that the simultaneous presence of both pollutants in water
      favours their adsorption and passing from water to the atmosphere through
      mechanisms such as bubbling.

PMID- 16084560
TI  - Evaluation of the toxicity of two soils from Jales Mine (Portugal) using aquatic
      bioassays.
AB  - Soil contamination can be one path for streams and groundwater contamination. As
      a complement of chemical analysis and total contaminants determination, bioassays
      can provide information on the bioavailable fraction of chemical compounds,
      focusing on the retention and habitat function of soils. In this study the
      evaluation of the toxicity of two soils from the abandoned Jales Mine (Portugal)
      regarded both functions. The buffer capacity of soils was tested with bioassays
      carried out using the cladoceran Daphnia magna and the marine bacteria Vibrio
      fischeri. The habitat function of soils was evaluated with the reproduction
      bioassay with the collembolan Folsomia candida. The Microtox solid-phase test was
      performed with V. fischeri using soil as test medium, and soil elutriates were
      extracted to perform the Microtox basic test, and an immobilization and
      reproduction bioassay with D. magna. The marine bacteria showed high sensitivity
      to the soil with low heavy metal content (JNC soil) and to JNC soil elutriates,
      while the soil with highest heavy metal content (JC soil) or soil elutriates
      exposure did not cause any toxic effect. In the bioassays with D. magna,
      organisms showed sensitivity to JNC and also to JC soil elutriates. Both
      mobilization and reproduction features were inhibited. The bioassay with F.
      candida did not reflect any influence of the contaminants on their reproduction.
      Although JNC soil presented lower heavy metal contents, elutriates showed
      different patterns of contamination when compared to JC soil and elutriates,
      which indicates different retention and buffer capacities between soils. Results
      obtained in this study underlined the sensitivity and importance of soil
      elutriate bioassays with aquatic organisms in the evaluation strategy in soil ERA
      processes.

PMID- 16084561
TI  - Speciation of Cd and Zn in contaminated soils assessed by DGT-DIFS, and
      WHAM/Model VI in relation to uptake by spinach and ryegrass.
AB  - A pot experiment was carried out to investigate the impact of Cd and Zn
      extractability in soil and speciation in pore water of industrial contaminated
      soils, on metal concentration in a metal sensitive species like spinach (Spinacia
      oleracea) and a more metal tolerant species like Italian ryegrass (Lolium
      multiflorum). For chemical speciation of Cd and Zn in pore water, WHAM/Model VI
      version 6.0 was used. The DGT technique was used to determine the effective
      concentration, C(E), of Cd and Zn in soils. The free ion activity in pore water
      correlated well with the contents in plants, and there was a linear relationship
      between the C(E) values and the concentration of Cd and Zn in both spinach and
      ryegrass in the non-toxic range. However, the C(E) values usually overestimated
      the plant contents when plants, particularly the spinach plants, were subjected
      to toxic concentration in the pore water. Metal uptake decreased in plants
      affected by toxicity, whereas metal binding to the Chelex resin did not. Thus, we
      found no linear relationship between the C(E) and metal contents in spinach,
      whereas a linear relationship was found between C(E)-Zn and the Zn concentration
      in ryegrass (r2=0.96, p<0.001). For Cd in ryegrass this relationship was weak
      (r2=0.53, p=0.18). This study indicates that the transport of metals from labile
      metal pools to the DGT-resin is linearly related to plant uptake only when plants
      are growing well, and that the applicability of DGT as an indicator for plant
      uptake seems species dependent.

PMID- 16084562
TI  - Total toxicity equivalents emissions of SF6, CHF3, and CCl2F2 decomposed in a RF
      plasma environment.
AB  - Sulfur hexafluorine compound (SF6), trifluoromethane (CHF3) and
      diclorodifluoromethane (CCl2F2) are extensively used in the semiconductor
      industry. They are global warming gases. Most studies have addressed the
      effective decomposition of fluorine compounds, rather than the toxicity of
      decomposed by-products. Hence, the concepts of toxicity equivalents (TEQs) were
      applied in this work. The results indicated that HF and SiF4 were the two
      greatest contributors of TEQ to the SF6/H2/Ar plasma system, while F2 and SiF4
      were the two greatest contributors to the SF6/O2/Ar system. Additionally, SiF4
      and HF were the two greatest contributors of TEQ to both the CHF3/H2/Ar and
      CHF3/O2/Ar plasma systems. HF and HCl were the two greatest contributors of TEQ
      to the CCl2F2/H2/Ar plasma system, and Cl2 and COCl2 were the two greatest
      contributors to the CCl2F2/O2/Ar system. HCl and HF can be recovered using wet
      scrubbing, which reduces the toxicity of these emission gases. Consequently, the
      hydrogen-based plasma system was a better alternative for treating gases that
      contained SF6, CHF3 and CCl2F2 from the TEQs point of view.

PMID- 16084563
TI  - Polybrominated diphenyl ethers in fish and wastewater samples from an area of the
      Penobscot River in central Maine.
AB  - Polybrominated diphenyl ethers (PBDEs) are one class of flame retardants commonly
      used in textiles, foams and plastics. They are similar in behavior to the well
      studied polychlorinated biphenyls and growing evidence suggests they are
      widespread global environmental pollutants that are capable of bioaccumulation.
      Fish tissue samples were collected from sites along the Penobscot River in
      central Maine. The total concentration of tetra- to hepta-PBDEs in these samples
      were calculated and generally increased from upstream to downstream locations
      ranging from 800 to 1810 ng/g lipid at the northernmost site to 5750-29000 ng/g
      at the downstream sampling site. BDE-47, 99 and 100 were the predominant
      congeners found in the fish tissue. Wastewater treatment plants (WWTPs) are one
      of the potential sources of these compounds to the environment through effluent
      discharge and landspreading of biosolids. Influent, effluent, activated sludge
      and dewatered biosolids were collected and analyzed for PBDE congeners from a
      WWTP at Orono, Maine. PBDE congeners were detectable in effluent samples at
      concentrations from 0.31 to 0.90 microg/l, in the activated sludge at 1.32-3.8
      microg/l and in the influent at 4.2-4.3 microg/l, but the majority of the
      material was concentrated in the biosolids. Total concentration in the biosolids
      was 2320-3530 microg/kg dry weight.

PMID- 16084564
TI  - Volatile carbonylic compounds in downtown Santiago, Chile.
AB  - Formaldehyde, acetaldehyde, acetone, propanal, butanal, 2-butenal, 3
      methylbutanal, hexanal, benzaldehyde, 2-methylbenzaldehyde, and 2,5
      dimethylbenzaldehyde were measured during six spring days at downtown Santiago de
      Chile. Measurements were performed 24h/day and averaged over three hour periods.
      The averages of the maxima (ppbv) were, formaldehyde: 3.9+/-1.4; butanal: 3.3+/
      3.4; acetaldehyde: 3.0+/-0.9; acetone: 2.4+/-1.0; 2-butenal: 0.56+/-0.52;
      propanal: 0.46+/-0.21; benzaldehyde: 0.34+/-0.3; 3-butanal: 0.11+/-0.05; hexanal:
      0.11+/-0.08; 2-methylbenzaldehyde: 0.08+/-0.05; 2,5-dimethylbenzaldehyde: 0.05+/
      0.03. Aliphatic aldehydes (C1-C3) are strongly correlated among them and weakly
      with primary (toluene) and secondary (ozone plus nitrogen dioxide or PAN)
      pollutants. In particular, the correlation between acetaldehyde and propanal
      values remains even if diurnal and nocturnal data are considered separately,
      indicating similar sources. All these aldehydes present maxima values in the
      morning (9-12h) and minima at night (0-3h). The best correlation is observed when
      butanal and 2-butenal data are considered (r=0.99, butanal/2-butenal=6.2). These
      compounds present maxima values during the 3-6h period, with minima values in the
      0-3h period. These data imply a strong pre-dawn emission. Other aldehydes show
      different daily profiles, suggesting unrelated origins. Formaldehyde is the
      aldehyde whose concentration values best correlate with the levels of oxidants.
      The contribution of primary emissions and photochemical processes to formaldehyde
      concentrations were estimated by using a multiple regression. This treatment
      indicates that (32+/-16)% of measured values arise from direct emissions, while
      (79+/-23)% is attributable to secondary formation.

PMID- 16084565
TI  - Effects of arbuscular mycorrhizal inoculation on uranium and arsenic accumulation
      by Chinese brake fern (Pteris vittata L.) from a uranium mining-impacted soil.
AB  - A glasshouse experiment was conducted to investigate U and As accumulation by
      Chinese brake fern, Pteris vittata L., in association with different arbuscular
      mycorrhizal fungi (AMF) from a U and As contaminated soil. The soil used contains
      111 mg U kg(-1) and 106 mg As kg(-1). P. vittata L. was inoculated with each of
      three AMF, Glomus mosseae, Glomus caledonium and Glomus intraradices. Two
      harvests were made during plant growth (two and three months after
      transplanting). Mycorrhizal colonization depressed plant growth particularly at
      the early stages. TF (transfer factor) values for As from soil to fronds were
      higher than 1.0, while those for roots were much lower. Despite the growth
      depressions, AM colonization had no effect on tissue As concentrations.
      Conversely, TF values for U were much higher for roots than for fronds,
      indicating that only very small fraction of U was translocated to fronds (less
      than 2%), regardless of mycorrhizal colonization. Mycorrhizal colonization
      significantly increased root U concentrations at both harvests. Root colonization
      with G. mosseae or G. intraradices led to an increase in TF values for U from 7
      (non-inoculation control) to 14 at the first harvest. The highest U concentration
      of 1574 mg kg(-1) was recorded in roots colonized by G. mosseae at the second
      harvest. The results suggested that P. vittata in combination with appropriate
      AMF would play very important roles in bioremediation of contaminated
      environments characterized by a multi-pollution.

PMID- 16084566
TI  - Henry's law constants and mass transfer coefficients for methyl bromide and 1,3
      dichloropropene applied to Florida sandy field soil.
AB  - Methyl bromide, a pre-emergent soil fumigant, is scheduled to be phased out in
      the US by 2005, with exceptions for critical use. Comparison of some of the
      physical constants related to distribution and retention for methyl bromide (MBr)
      to other fumigants yields a useful quantification of possible alternatives. In
      this study, the atmospheric and subsurface dissipation of methyl bromide as well
      as (Z)- and (E)-1,3-dichloropropene (1,3-D) isomers in Telone II were examined.
      The Henry's law constants of the three chemicals at soil temperature and their
      mass transfer coefficients for movement through an agricultural mulch of UV
      resistant, high-density polyethylene (PE) were evaluated using field data. At the
      soil temperature of 16.4 degrees C, calculated Henry's law constant gave a
      fumigant ranking of MBr (0.21)>>(Z)-1,3-D (0.041)>(E)-1,3-D (0.027). Since rapid
      subsurface distribution of a fumigant is highly dependent on the amount in the
      gas phase, the greater value for Henry's law constant implies faster distribution
      throughout the soil. After distribution through the soil, retention of the
      fumigant becomes imperative. Calculation of the fumigant's mass transfer
      coefficients through PE from field data gave a ranking of the three chemicals:
      MBr (1.08 cm/h)<(E)-1,3-D (3.25 cm/h)<(Z)-1,3-D (4.13 cm/h). With mass transfer
      coefficients of this magnitude, it was concluded that PE film was an inadequate
      barrier for retaining these fumigants in an agricultural setting.

PMID- 16084567
TI  - Gyrineum natator: a potential indicator of imposex along the Indian coast.
AB  - Imposex related studies have used neogastropods as sentinel organism. In this
      effort, we elucidate the potential of a mesogastropod, Gyrineum natator, for
      imposex monitoring on the central west coast of India. Observations were made
      with specimens collected from Mumbai (three stations), Ratnagiri (two stations),
      Goa (one station) and Mangalore (one station). The analyzed populations at all
      four sites were affected by imposex. The six different stages of imposex in this
      organism are illustrated through schematic and scanning electron micrographs. In
      view of the anticipated ban on TBT based antifouling paints this baseline
      information can serve as an indicator for environmental monitoring in this
      region.

PMID- 16084568
TI  - Environmental features of two commercial surfactants widely used in soil
      remediation.
AB  - One of the main limitations for a wider application of surfactants in soil
      remediation is the lack of knowledge about environmental fate and toxicity of
      surfactant itself especially for in situ application. Sorption behaviour,
      biodegradability, toxicity of parent compound and its metabolites are important
      processes that affect environmental fate of surfactants in site remediation
      applications. Tween 80 (poly(oxyethylene)(20)-sorbitane monooleate) and Aerosol
      MA+80 (dihexyl sodium sulfosuccinate) are surfactants that have been tested in
      laboratory and field scale remediation of soil and groundwater. In this work, the
      sorption and biodegradability of these surfactants were assessed to provide
      conditions and limitations for their use. The soil used in this experimentation
      was analysed for organic carbon content, soil bacteria, and size fraction and
      resulted to be a good model because is characterised by mean values for almost
      all considered parameters. Tween 80 showed high degree of biodegradability but a
      high affinity for soil matrix. Results suggest that Tween 80 could find its best
      application in ex situ solid phase remediation like ex situ bioremediation; its
      high affinity to soil could limit in situ applications. Biodegradation tests for
      Aerosol MA+80 show low degree of biodegradability and mineralisation.
      Biodegradation experiments, coupled with analysis of toxicity, could support the
      hypothesis that degradation of Aerosol MA+80 is not complete and leads to an
      accumulation of intermediates with at least the same toxicity of the parental
      compound. Therefore, aquifer remediation application with Aerosol MA+80 has to be
      conducted with necessary precautions to avoid product loss and excess surfactant
      should be flushed from the soil.

PMID- 16084569
TI  - Human milk survey for dioxins in the general population in Japan.
AB  - BACKGROUND: Much attention has been paid to the level of dioxins in breast milk
      in Japan but few large-scale studies have been conducted on the subject. METHODS:
      From 1997 to 2002, we collected 839 samples of breast milk from primiparas
      residing throughout Japan. Starting in 1999, breast milk was also collected from
      secundiparas. Seven isomers of polychlorinated dibenzo-p-dioxins (PCDDs), 10 of
      polychlorinated dibenzofurans (PCDFs), 4 of coplanar polychlorinated biphenyls
      (Co-PCBs) and 8 of mono-orthochlorinated polychlorinated biphenyls (mono-ortho
      PCBs) were analyzed by employing gas chromatography and mass spectrometry. A
      correlation between the level of dioxins in human milk and the age of the mothers
      was noted for the primiparas and the secundiparas; and the levels were compared
      between the first and the second deliveries. Grouped by parity and prefecture in
      each year, observations were also made on the trends in these levels. Dioxin
      levels are shown by using geometric means because their distributions were skewed
      to the left. RESULTS: The sum of PCDDs and PCDFs, Co-PCBs, mono-ortho PCBs, and
      total dioxins in the breast milk of primiparas were 13.9, 5.4, 3.4, and 22.7 pg
      TEQ/g fat, respectively. In the samples obtained from secundiparas, these levels
      were 63-68 percents of those taken from the primiparas. The correlation
      coefficients between the PCDDs/DFs, Co-PCBs, mono-ortho PCBs, and total dioxins
      and the age of the primiparas were 0.19, 0.17, 0.36, and 0.24, respectively. All
      these correlations were statistically significant (p < 0.001). The positive
      correlations between these contaminants and the age of the secundiparas were also
      examined. The total dioxins as well as PCDDs/DFs, Co-PCBs, and mono-ortho PCBs in
      the breast milk of the primiparas declined significantly between 1998 and 2002
      (regression coefficients: -0.04, -0.05, -0.03, and -0.03, respectively). However,
      no significant decline in these levels was observed when sorted by prefectures.
      CONCLUSIONS: Much attention should be paid to the age and parity of nursing
      mothers when investigating the relationship between the level of dioxins in
      breast milk and the body burden of infants.

PMID- 16084570
TI  - Gross alpha and beta activities in tap waters in Eastern Black Sea region of
      Turkey.
AB  - Gross alpha and gross beta activities were determined for 27 different tap water
      samples collected from Eastern Black Sea region of Turkey. The instrumentation
      used to count the gross alpha and gross beta activities was a alpha/beta counter
      of the low background multiple detector type with 10 sample detectors (Berthold
      LB770). The obtained results showed that natural activity concentrations of alpha
      and beta-emitting radionuclides in tap water samples did not exceed WHO and ITS
      recommended levels. Concentrations ranging from 0.2 mBq/l to 15 mBq/l and from
      25.2 mBq/l to 264.4 mBq/l were observed for the gross alpha and gross beta
      activities, respectively. For all samples the gross beta activities were higher
      than the corresponding gross alpha activities.

PMID- 16084571
TI  - Interval estimation of urban ozone level and selection of influential factors by
      employing automatic relevance determination model.
AB  - In this work, we focus on simulating the ground-level ozone (O3) time series and
      its daily maximum concentration in Hong Kong urban air by employing the
      multilayer perceptron (MLP) model combined with the automatic relevance
      determination (ARD) method (for simplicity, we name it as MLP-ARD model). Two air
      quality monitoring sites in Hong Kong, i.e., Tsuen Wan and Tung Chung, are
      selected for the numerical experiments. The MLP-ARD model based on Bayesian
      evidence framework can provide reliable interval estimation of real observation
      as well as offering efficient strategy to avoid over-fitting. The performance
      comparisons between MLP-ARD model and traditional artificial neural network (ANN)
      model based on maximum likelihood indicate that MLP-ARD model is more powerful to
      capture the wild fluctuation of O3 level especially during O3 episodes than the
      traditional model. Furthermore, it can assess and rank the input variables for
      the prediction according to their relative importance to the output variable,
      i.e., the daily maximum O3 concentration in this study. The preliminary
      experimental results indicate that nitric oxide (NO) and solar radiation are the
      most important input variables for O3 prediction at both selected sites. In
      addition, the previous daily maximum O3 level is also important for Tung Chung
      site. In this regard, MLP-ARD model is a feasible tool to interpret the real
      physical and chemical process of urban O3 variation.

PMID- 16084572
TI  - Oxidative stress in Scenedesmus sp. during short- and long-term exposure to Cu2+
      and Zn2+.
AB  - Algae are exposed to elevated levels of heavy metals in water bodies generally
      for a long-term, and occasionally for a short-term duration. The present study
      deals with oxidative stress in Scenedesmus sp., commonly found in nutrient-rich
      freshwaters, during short- (6h) and long-term (7d) exposure to Cu(2+) and Zn(2+).
      The cells accumulated almost 2- and 4-times more Cu(2+) and Zn(2+) inside the
      cells during long-term than during short-term exposure to these metals. But the
      data on photosynthetic O(2) evolution and cell viability suggest that Scenedesmus
      sp. experienced lesser metal stress in long-term than in short-term experiment.
      Although malondialdehyde content was slightly higher in the long-term experiment,
      the amount produced by one unit intracellular metal was significantly lower than
      that in the short-term experiment. Superoxide dismutase activity of Scenedesmus
      sp. was >30% higher during long-term than during short-term exposure to Cu(2+)
      and Zn(2+). But, catalase and ascorbate peroxidase activities increased only at
      2.5 microM Cu(2+) and 25 microM Zn(2+) when oxidative stress was mild, but were
      inhibited at 10 microM Cu(2+) under intense oxidative stress. Cu(2+) and Zn(2+)
      reduced glutathione reductase activity and total SH content of Scenedesmus sp. in
      both the experiments, with greater reduction occurring in the long-term
      experiment. The depletion of total thiol was positively related with the
      intracellular level of metals. Thiols might have helped Scenedesmus sp. in
      overcoming metal-induced oxidative stress, but depletion of thiol pool is known
      to make cells vulnerable to oxidative stress. The study suggests that antioxidant
      enzymes play a role only under mild oxidative stress. An increased accumulation
      of proline seems to be an important strategy for alleviating metal-induced
      oxidative stress in Scenedesmus sp. The study shows that Scenedesmus sp. could
      acclimatize during long-term exposure to toxic concentrations of the test metals.

PMID- 16084573
TI  - Differences in the platelet reactivity response to mental stress in cardiac
      syndrome X patients compared to known coronary artery disease patients: concepts,
      explanations and methodological weaknesses.

PMID- 16084574
TI  - Regulation of gene and protein expression in cardiac myocyte hypertrophy and
      apoptosis.
AB  - Considerable efforts have been expended in elucidating the inter-cellular and
      intra-cellular signaling pathways which elicit cardiac myocyte hypertrophy or
      apoptosis, and in identifying the changes which are associated with the end-stage
      of the response. The challenge now is to link the two. Although some of the
      signaling effects will be the acute modulation of existing protein function, long
      term effects which bring about and maintain the hypertrophic state or which
      culminate in cell death are mediated at the level of gene and protein expression.
      With the advances in micro-array technology and genome sequencing, it is now
      possible to obtain a picture of the global gene expression profile in myocytes or
      in whole heart which dictates the proteins which could be made. This is not the
      final picture since additional regulation at the level of translation modulates
      the relative proportions of each protein that can be made from the transcriptome.
      Even here, further regulation of protein stability and turnover means that
      ultimately it is still necessary to examine the proteome to determine what may
      cause the functional changes in a cell. Thus, in order to gain a full picture of
      events which regulate the response and gain some insight into possible points of
      intervention for therapy, it is necessary to examine gene expression, mRNA
      translation and protein expression in concert.

PMID- 16084575
TI  - Germline mutations of BRCA1 and BRCA2 in Korean sporadic ovarian carcinoma.
AB  - OBJECTIVES: Mutations in the BRCA1 and BRCA2 genes predispose women to ovarian
      and/or breast cancer. The contribution of BRCA1 and BRCA2 mutations to ovarian
      cancer in Korean women remains to be elucidated. In addition, genetic
      polymorphisms may affect not only cancer development but also cancer progression
      and, as a result, could influence cancer phenotypes. The purposes of this study
      were, first, to investigate the presence of BRCA1 and BRCA2 mutations in women
      with ovarian cancer who were unselected for family history and, second, to
      evaluate the relationship between ovarian cancer susceptibility gene
      polymorphisms and clinicopathological features. METHODS: We studied 37 women who
      were diagnosed with epithelial ovarian cancer and treated at the Yonsei
      University Hospital between August 2002 and March 2004. Genomic DNA was analyzed
      for BRCA mutations using a PCR-DHPLC-sequencing method. The relationship between
      ovarian cancer susceptibility gene polymorphisms and clinicopathological features
      was examined. RESULTS: Most mutations of BRCA1 and BRCA2 associated with ovarian
      and/or breast cancer result in truncated proteins. We found one frameshift
      mutation in BRCA1 (3746insA) that led to premature termination. The patient had
      no family history of breast or ovarian cancer. There was no relationship between
      ovarian cancer susceptibility gene polymorphisms and clinicopathological
      features. CONCLUSION: Our results were consistent with the hypothesis that BRCA1
      and BRCA2 mutations have a limited role in sporadic ovarian carcinogenesis in the
      Korean population. Furthermore, polymorphisms of certain, selected ovarian cancer
      susceptibility genes were not associated with the clinicopathological phenotypes
      of ovarian cancer.

PMID- 16084576
TI  - The accuracy of examination under anesthesia and transvaginal sonography in
      evaluating ovarian size.
AB  - OBJECTIVE: To compare pelvic examination under anesthesia to transvaginal
      sonography (TVS) as a method for ovarian detection and measurement. METHODS: Two
      hundred and eighty-nine ovaries from 151 women were evaluated. After induction of
      anesthesia, a complete pelvic examination and TVS were performed, and the ovaries
      were removed surgically. Ovarian dimensions generated sonographically and
      estimated on clinical examination were compared to those obtained from the
      measured surgical specimen. RESULTS: Forty-four percent of ovaries were palpable
      clinically whereas 85% were visualized sonographically (P < 0.001). Right ovaries
      were palpable more frequently than left ovaries (P < 0.01). Ovaries were detected
      clinically in 30% of women > or = 55 years of age versus 51% of women <55 years
      of age (P < 0.05), in 9% of women weighing > or = 200 lb versus 55% of women
      weighing <200 lb (P < 0.001), and in 12% of women with a uterine weight > or =
      200 g versus 51% of women with a uterine weight <200 g (P < 0.001). TVS was
      significantly more accurate than clinical examination in detecting ovaries in
      women with these high risk characteristics. CONCLUSIONS: TVS is significantly
      more accurate than clinical examination in detecting ovaries and in defining
      their dimensions. Ovaries frequently are not palpable in women > or = 55 years of
      age, women who weigh > or = 200 lb, or women with an enlarged uterus (> 200 g).
      The addition of TVS to annual pelvic examination may be beneficial in women > or
      = 55 years of age who are overweight and therefore at high risk to develop
      ovarian cancer.

PMID- 16084577
TI  - Successful pig embryonic development in vitro outside a CO2 gas-regulated
      incubator: effects of pH and osmolality.
AB  - We investigated the effects of HEPES in the medium (to maintain pH) and paraffin
      oil covering the medium (to maintain osmolality) on the developmental ability of
      porcine embryos produced in vitro using tightly closed glass tubes in the absence
      of a CO2 gas-regulated incubator. Putative porcine zygotes obtained by in vitro
      fertilization (IVF) of in vitro-matured (IVM) oocytes (day of IVF=Day 0) were
      cultured in 5% CO2 gas-equilibrated NCSU-37 media containing pyruvate and lactate
      during Days 0-2, and glucose during Days 2-6, in open glass tubes in a CO2
      incubator or tightly closed glass tubes without a CO2 incubator at 38.5 degrees
      C. The following four media were used: (1) medium covered with paraffin oil and
      supplemented with HEPES; (2) medium covered with paraffin oil but with no HEPES
      supplementation; (3) medium not covered with paraffin oil but supplemented with
      HEPES; (4) medium not covered with paraffin oil and with no HEPES
      supplementation. As a control group, zygotes were cultured in medium with neither
      paraffin oil coverage nor HEPES supplementation using a four-well dish in a CO2
      gas-regulated incubator. After culture, the osmolality in each of the four closed
      conditions was maintained at approximately 285-286 mOsm, lower (P<0.05) than that
      in the control (291 mOsm). In the two HEPES-supplemented media groups in the
      closed-tube system, the pH was maintained at 7.5-7.7, and the blastocyst
      development rates (15.5% in non-oil covered and 18.5% in oil covered group) did
      not differ significantly from that of the control (20.2%), although the mean cell
      numbers in the blastocysts in the two closed-tube condition groups (28.2 and
      33.0) were lower (P<0.05) than in the control (43.5). In contrast, the pH was
      higher in the two groups without HEPES supplementation (approximately 8.0) than
      the control (7.4; P<0.05), and the blastocyst development rates (10.9% in non-oil
      covered and 7.5% in oil covered group) or total cell numbers in the blastocyst
      (24.8 and 28.7) in the two non-HEPES groups were drastically decreased (P<0.05)
      compared to those in the control (20.2% and 43.5). These results suggested that
      maintenance of pH is important for successful in vitro porcine embryo culture
      under closed-air conditions, whereas the range of osmolality that suits embryo
      development is not limited to a small range. Furthermore, blastocyst production
      was possible in a glass tube without a CO2 incubator, although blastocyst quality
      was lower compared to those produced in an incubator.

PMID- 16084578
TI  - Is the yak (Poephagus grunniens L.) really a seasonal breeder?
AB  - Yaks are considered to be seasonally polyestrous and breeding occurs from July to
      November. Here we show that some yaks in peak non-breeding season do exhibit
      cyclic luteal activity without exhibiting any behavioral signs around expected
      estrus. A total of eight non-lactating yaks were selected from the Yak Farm
      belonging to National Research Centre on Yak for various sets of experiments. The
      animals were maintained as per semi range system of management. They were allowed
      to graze during daytime and fed concentrate mixture @2 kg/animal/day as per
      standard farm practices of the center. Blood samples were collected on alternate
      days for 30 days by jugular venipuncture from the yaks during peak breeding
      season (July to November) and from the same yaks in non-breeding season (February
      to March). The plasma samples were analysed for progesterone and estradiol-17beta
      by RIA and EIA procedures, respectively. During breeding season, the mean plasma
      progesterone at estrus was basal (<or=0.2 ng/ml) and there after started to
      increase and reached a peak at days 15-16 of the cycle and then declined rapidly
      to basal levels at estrus. Mean plasma estradiol-17beta concentrations were high
      at estrus and then declined to basal level at days 2-3 of the cycle. The mean
      plasma estradiol-17beta concentrations stayed low for the remaining part of the
      estrous cycle except for a small elevation, which was exhibited between days 6
      and 12 of the cycle. During non-breeding season, in 50% of the animal studied,
      plasma progesterone and estradiol-17beta levels were at basal level. However, in
      the remaining animals distinct luteal activity was recorded in terms of plasma
      progesterone profile. High concentrations of progesterone were maintained in one
      animal, which suggested existence of cystic corpus luteum. The trend of
      progesterone and estradiol-17beta profiles in other three animals indicated that
      they could be cycling although they did not exhibit estrus symptoms. It was
      concluded from the present study that with improved nutritional support some yaks
      exhibit estrous cyclicity even during the non-breeding period of the year.

PMID- 16084580
TI  - Corrosion potential variation of aged dental amalgam restorations over time.
AB  - OBJECTIVE: The corrosion potential of a dental amalgam restoration is generally
      determined using a single measurement, even though environmental factors and
      abrasion can continuously alter the surface state and reactivity of this alloy.
      It was, therefore, the purpose of this study to determine the maximum variability
      of the corrosion potential of aged dental amalgam restorations, for 28 days.
      METHODS: The corrosion potentials of 148 aged dental amalgam restorations in 12
      human subjects were measured at t = 0 and 4 h, and 4, 7, 14, 21 and 28 days.
      Measurements were made with a high impedance voltmeter and a Ag/AgCl micro
      reference electrode. The subjects were instructed not to alter their usual eating
      and oral hygiene routines. RESULTS: Corrosion potential changes occurred
      throughout the 28 days. They were both positive and negative for the same
      restoration, and were sometimes very large. Only 4 h after the initial
      measurement, the absolute value of the corrosion potential changes ranged between
      18 and 287 mV for 50% of the restorations. The largest maximum absolute corrosion
      potential change for each subject's restorations ranged between 85 and 329 mV.
      Statistical analysis showed that the overall mean maximum absolute corrosion
      potential change for the subjects' restorations was 74 mV. SIGNIFICANCE: It was
      shown that the corrosion potential of aged dental amalgam restorations varies
      substantially over time, and that a single measurement is not representative of
      short- or long-term electrochemical behavior. This finding has implications
      regarding the corrosion rate of dental amalgam restorations, particularly those
      that are part of a galvanic couple.

PMID- 16084579
TI  - Comparison of hemispheric activation during mental word and rhyme generation
      using transcranial Doppler sonography.
AB  - The Wada test is at present the method of choice for preoperative assessment of
      patients who require surgery close to cortical language areas. It is, however, an
      invasive test with an attached morbidity risk. By now, an alternative to the Wada
      test is to combine a lexical word generation paradigm with non-invasive imaging
      techniques. However, results of this approach are still not in complete agreement
      with the findings of the Wada test (r = .92; Knecht, Deppe, Ebner et al., 1998).
      We attempted to obtain a more distinct language lateralization with the
      development of a phonological rhyme generation paradigm based on pseudoword
      stimuli. To examine the predictive value of both paradigms we performed
      simultaneous bilateral functional transcranial Doppler ultrasonography on 19
      right-handed male native German subjects. The rhyme generation condition produced
      a significantly stronger lateralization to the supposed hemisphere of language
      dominance than the classical word generation condition. The observed differences
      suggest that the rhyme generation paradigm is more robust in detecting
      hemispheric language dominance than other neuropsychological paradigms and might
      be most valuable for preoperative assessment of cortical language areas.

PMID- 16084581
TI  - Metameric effect between resin composite and dentin.
AB  - OBJECTIVES: The purpose of this study was to determine the metameric color
      differences between resin composites and dentin. METHODS: Spectral reflectance
      and color of five shades of one brand of resin composite were measured according
      to the CIELAB color scale relative to the standard illuminant D65, A and F2.
      Average values of human dentin were used as the optical properties of dentin.
      Color differences (deltaE(ab)*) between resin composite and dentin relative to
      three illuminants were calculated, and ratio of deltaE(ab)* values by the
      illuminant (A/D65 and F2/D65) was calculated. Ratios of changes in hue angle of
      resin composites by illuminant over those of dentin were compared. RESULTS: In
      curves of spectral reflectance, three of five shades made more than three
      crossing points with dentin indicating a metameric effect. Color differences
      between resin composite and dentin was changed when illuminant were changed from
      daylight (D65) to incandescent light (A) or fluorescent light (F2). Ratios of
      deltaE(ab)* value between resin composite and dentin by the illuminant were 0.74
      0.98. Color difference relative to D65 was larger than those for illuminants A
      and F2. Differences in hue angle (value relative to illuminant A-that to D65) of
      resin composites were in the range from -10.1 to -7.2 (-13.8 to -14.0 in dentin),
      and those between F and D65 were 2.6-5.2 (-3.9 to -2.8 in dentin). SIGNIFICANCE:
      Changes in optical properties of resin composites relative to the different
      illuminants were different from those of dentin; therefore this inconsistency
      should be considered in shade matching of resin composites.

PMID- 16084582
TI  - Surface roughness and gloss of dental materials as a function of force and
      polishing time in vitro.
AB  - OBJECTIVES: The purpose of this study was (1) to analyze the influence of
      polishing time and press-on force on the surface gloss and roughness of dental
      materials by using a three-component rubber-based polishing system and to compare
      the results with those obtained in conjunction with an optimal polishing
      procedure and application of the specimens to a metal matrix, (2) to estimate the
      correlation between surface gloss and surface roughness. METHODS: Eight flat
      specimens were made of each dental material (Tetric Ceram [TC], Tetric EvoCeram
      [TE], Heliomolar [HM], Compoglass [CO] and Amalcap [AM]) and polished with 4000
      grit SiC and a polishing liquid. Subsequently, the mean surface roughness (Ra)
      was measured with an optical sensor (FRT MicroProf) and the gloss (Gl) with a
      glossmeter (Novocurve). Prior to polishing the specimens with the polishing
      system, the surface was pre-roughened with 320-grit SiC paper and polishing was
      performed under water cooling at 10,000rpm, applying a controlled force of 2N.
      Each component of the Astropol system (F/P/HP) was used for 30s and Ra and Gl
      were measured at 5-second intervals. Other specimens of the same materials were
      polished with a controlled force of 4N or they were applied to a metal matrix
      and, subsequently, Ra and Gl were measured. To measure the influence of the
      polishing time on the surface gloss and roughness, repeated ANOVA with post-hoc
      paired t-tests was carried out in log-transformed Ra and gloss values. To
      estimate the correlation between Ra and Gl, the Spearman and Pearson correlation
      was calculated. RESULTS: (1) Surface gloss and surface roughness were time
      dependent, showing the greatest improvement already after 5s of polishing with
      each of the polishing components, with the exception of AM, for which HP was not
      effective. The patterns of improvement varied considerably from material to
      material, but they were more consistent with regard to Gl than to Ra. (2) Ra was
      statistically significantly higher only in TC, TE and CO when 4N of force was
      applied instead of 2N. (3) Polishing the surface with a polishing machine
      resulted in a significantly better surface gloss in all materials. (4) After
      applying the specimens to a metal matrix, the surface roughness of all dental
      materials was significantly higher when compared to polished specimens except for
      TC. (5) Correlations between gloss and roughness were in general negative but
      they were higher for individual measurements compared to the differences between
      two consecutive measurements. SIGNIFICANCE: Both surface gloss and surface
      roughness were material-dependent and influenced by the polishing time and
      applied force. As gloss and roughness proved to be closely associated with each
      other, gloss assessment may be a sufficient method to screen materials with
      regard to their polishability.

PMID- 16084583
TI  - Effect of topical fluoride application on toothbrushing abrasion of resin
      composites.
AB  - OBJECTIVES: This in vitro study assesses toothbrushing abrasion of a microfill
      (Heliomolar Radioopaque) and a hybrid composite (Herculite XRV) after application
      of two acidic fluoride agents. METHODS: Thirty-six specimens of each resin
      composite were fabricated, ground flat and polished. Subsequently the 36 samples
      of each material were evenly assigned to three groups. In the first group,
      samples were treated with the fluoride varnish Bifluorid 12 (5.5% F, pH 5.6), in
      the second group with Elmex Fluid (1.25% F, pH 4.3). In the third group,
      specimens remained unfluoridated (controls). After 8h, the samples were subjected
      to toothbrushing abrasion (2000 brushing strokes, load: 250 g) in an abrasive
      slurry. Fluoridation and brushing abrasion were repeated twice. Afterwards,
      abrasion of the materials was quantitatively determined with a laser profilometer
      and statistically analyzed (ANOVA). RESULTS AND SIGNIFICANCE: With Herculite
      both, Bifluorid 12 (P = 0.0001) and Elmex Fluid (P = 0.0001) led to a significant
      increase of brushing abrasion compared to the non-fluoridated group. However, no
      significant difference was observed between the two fluoridation regimes.
      Heliomolar showed a tendency towards higher abrasion after treatment with Elmex
      Fluid compared to Bifluorid 12 (P = 0.0496) and the non-fluoridated group (P =
      0.0496), whereas treatment with Bifluorid 12 yielded no significant difference
      compared to the non-fluoridated Heliomolar specimens. Fluoridation of Herculite
      resulted in a 106-121% increase of abrasion, whereas Heliomolar only showed an
      increase by 5-30%. Application of the acidic fluoride products used led to an
      increase in toothbrushing abrasion of the tested composite restorative materials.
      However, clinical long-term studies are needed to determine the effect of topical
      fluoride regimes on resin composite materials.

PMID- 16084584
TI  - Flowable materials as an intermediate layer could improve the marginal and
      internal adaptation of composite restorations in Class-V-cavities.
AB  - OBJECTIVES: The purpose of this in vitro study was to evaluate the marginal and
      internal adaptation of restorative systems in combination with flowable materials
      as an intermediate layer in Class-V-cavities. METHODS: Thirty Class-V-cavities
      with occlusal margins in enamel and gingival margins in dentin/cementum were
      prepared and randomly assigned to five groups. The following five restorative
      systems were used: compomer, composite E, flowable compomer/composite E,
      composite RF and flowable composite/composite RF. The flowable materials were
      added between the restorative composites and the cervical margins of the
      cavities. Marginal and internal adaptation were quantitatively evaluated before
      and after thermal (2,500 times between 5 and 55 degrees C) and mechanical load
      cycling (25,000 times 100 N) using standard SEM procedures. Statistical analysis
      was performed using the Kruskal-Wallis and Mann-Whitney U-Test. The morphology of
      the internal restorative interfaces was also evaluated. RESULTS: The present
      study revealed that the best marginal adaptation in dentin was attained with the
      compomer restoration (95.8% perfect margin). The marginal adaptation of composite
      restorative systems was improved by the use of a flowable compomer (45.5% vs.
      68.2% perfect margin in dentin) or a flowable composite (46.7% vs. 80.7% perfect
      margin in dentin, p<0.05) as an intermediate layer. No differences were observed
      between the used materials for the parameter internal adaptation. SIGNIFICANCE:
      In Class-V-cavities compomers showed the best marginal adaptation and the
      marginal adaptation of composite fillings could be improved by the use of
      flowable materials as an intermediate layer.

PMID- 16084585
TI  - Wear of resin denture teeth by two-body contact.
AB  - OBJECTIVES: The objective of this study was to examine the two-body wear
      resistance of nine different resin denture teeth and one experimental material.
      METHODS: The two-body wear test was performed in a chewing simulator with an
      antagonistic Al(2)O(3) ball under an axial load of 40 N for 100,000 cycles. In
      each test series, an enamel sample was included as a reference. The wear was
      determined with an optical 3D surface profilometer. For statistical evaluation,
      SPSS for Windows was used. RESULTS: The samples of Artiplus (18.7-SD 21.0) and e
      Ha (21.2-SD 15.1) showed the lowest volumetric wear (in mm(3)x10(-3)) after
      100,000 cycles. The difference from the other materials tested, except NC Veracia
      Posterior, was statistically significant (p=0.001-0.037). SR-Postaris-DCL (55.0
      SD 6.8), SR-Orthosit-PE (61.1-SD 12.4) and Vitapan (72.1-SD 15.9) exhibited
      medium-sized wear values with low dispersion, whereas Orthognat (80.1-SD 31.6),
      Premium 8 (84.6-SD 31.4), NC Veracia Posterior (87.0-SD 52.7), SR-Orthotyp-PE
      (114.6-SD 28.0) and Trubyte Portrait (123.0-SD 45.6) showed high wear values with
      great variations. Statistically provable differences were found between SR
      Orthotyp-PE and SR-Postaris-DCL (p=0.019) and also between SR-Orthotyp-PE and SR
      Orthosit-PE (p=0.031). For enamel, a medium-sized wear value of 66.1-SD 76.8 was
      determined. SIGNIFICANCE: The denture teeth examined showed differences in two
      body wear resistance. The wear values determined were in some cases higher and in
      others lower than those of natural enamel. A definite connection between the wear
      resistance and the chemical composition of the materials could not be found in
      this investigation.

PMID- 16084586
TI  - Galactose-carrying polymers as extracellular matrices for liver tissue
      engineering.
AB  - Extracellular matrix (ECM) plays important roles in tissue engineering because
      cellular growth and differentiation, in the two-dimensional cell culture as well
      as in the three-dimensional space of the developing organism, require ECM with
      which the cells can interact. Especially, the bioartificial liver-assist device
      or regeneration of the liver-tissue substitutes for liver tissue engineering
      requires a suitable ECM for hepatocyte culture because hepatocytes are anchorage
      dependent cells and are highly sensitive to the ECM milieu for the maintenance of
      their viability and differentiated functions. Galactose-carrying synthetic ECMs
      derived from synthetic polymers and natural polymers bind hepatocytes through a
      receptor-mediated mechanism, resulting in enhanced hepatocyte functions.
      Attachment and functions of hepatocytes were affected by physico-chemical
      properties including ECM geometry as well as the type, density and orientation of
      galactose. Also, cellular environment, medium composition and dynamic culture
      system influenced liver-specific functions of hepatocytes beside ECM.

PMID- 16084587
TI  - Administration of the galanin antagonist M40 into lateral septum attenuates shock
      probe defensive burying behavior in rats.
AB  - Galanin (GAL) has been implicated in modulating anxiety, although a precise role
      remains unclear. Previous studies revealed anxiolytic effects, anxiogenic
      effects, or no effect, depending on the test, brain region, route of drug
      administration and context. We have shown previously that microinjection of the
      GAL antagonist M40 into central amygdala blocked an anxiolytic response to acute
      stress on the elevated plus maze when rats were pretreated with yohimbine,
      suggesting an anxiolytic effect of GAL. By contrast, we also showed that
      microinjection of M40 into the lateral bed nucleus of the stria terminalis
      attenuated anxiety-like behavioral responses to stress on the plus maze and
      social interaction tests, implying an anxiogenic effect for GAL. The behavioral
      response to stress on both these tests is a reduction of an ongoing behavior
      (open-arm exploration or social interaction, respectively). To better understand
      the anxiety-modulating role of GAL, it is also important to ascertain its effect
      on a response that represents an activation rather than suppression of behavior.
      Thus, in this study, we investigated an active behavioral response to acute
      stress in rats, the shock-probe defensive burying response. Bilateral
      microinjections of M40 into lateral septum (LS), a region important to this
      response and innervated by GAL, dose-dependently decreased burying without
      affecting immobility. No change was seen in hindpaw withdrawal latency on a
      thermosensitivity assay, suggesting that the reduction in burying behavior was
      not attributable to changes in cutaneous pain sensitivity. These results indicate
      that in LS, GAL facilitates the active anxiety-like behavioral response on the
      defensive burying test, similar to its facilitatory effect on anxiety-like stress
      induced suppression of behavior in the lateral bed nucleus. These results
      highlight the fact that, rather than a unified system-like role in modulating
      anxiety, the effects of GAL can be either facilitating or attenuating, and are
      region-specific, context-specific and response-specific.

PMID- 16084588
TI  - Antibody repertoire development in teleosts--a review with emphasis on salmonids
      and Gadus morhua L.
AB  - The group of teleosts is highly diverse, comprising more than 23000 extant
      species. Studies of the teleost antibody repertoire have been conducted in many
      different species within different orders, though some species and families have
      been better characterised than others. The Atlantic cod (Gadus morhua L.) and
      several species within the Salmoninae (e.g. Salmo salar and Oncorynchus mykiss)
      are among the best-studied teleosts in terms of the antibody repertoire. The
      estimated size of the repertoire, the organisation of immunoglobulin (IG) gene
      segments, the expressed IG repertoire, the IgM serum concentration, and the serum
      antibody responses reveal some fundamental differences between these species. The
      serum IgM concentration of G. morhua is some ten times higher than that of S.
      salar, though G. morhua is characterised as a 'low' (or 'non') responder in terms
      of specific antibody production. In contrast, an antibody response is readily
      induced in S. salar, although the response is strongly regulated by antigen
      induced suppression. The IGHD gene of G. morhua has a unique structure, while the
      IGHM and IGHD genes of S. salar have a characteristic genomic organisation in two
      parallel loci. In addition, salmonids, express a broad repertoire of IGH and IGI
      V-region gene segments, while a single V gene family dominates the expressed
      heavy and light chain repertoire of G. morhua. Little is known about the
      developing antibody repertoire during ontogeny, in different stages of B-cell
      maturation, or in separate B-cell subsets. Information on the establishment of
      the preimmune repertoire, and the possible role of environmental antigens is also
      sparse.

PMID- 16084589
TI  - Gabaergic regulation of the neural organization of fear in the midbrain tectum.
AB  - In midbrain tectum (MT) structures, such as the dorsal periaqueductal gray
      (dPAG), the superior colliculus (SC) and the inferior colliculus (IC) GABAergic
      neurons exert a tonic control on the neural substrates involved in the expression
      of defensive reactions. In this review, we summarize behavioral,
      immunohistochemical (brain Fos distribution) and electrophysiological (auditory
      evoked potentials) data obtained with the reduction of GABA transmission by local
      injections of a GABA receptor blocker (bicuculline, BIC) or a glutamic acid
      decarboxylase inhibitor (semicarbazide, SMC) into the MT. Distinct patterns of
      Fos distribution were obtained following the freezing and escape reactions
      induced by MT injections of SMC and BIC, respectively. While only the
      laterodorsal nucleus of the thalamus was labeled after SMC-induced freezing, a
      widespread increase in Fos expression in the brain occurred after BIC-induced
      escape. Also, injections of SMC into the IC increased the auditory evoked
      potentials recorded from this structure. It is suggested that GABAergic
      mechanisms of MT are also called into play when sensory gating of the MT is
      activated during different emotional states.

PMID- 16084590
TI  - Concurrent conditioned taste aversion: a learning mechanism based on rapid neural
      versus flexible humoral processing of visceral noxious substances.
AB  - Taste aversion learning (TAL) consists of the avoidance of a taste previously
      associated with a noxious visceral stimulus. Clinical and experimental studies
      suggest that this adaptive process can be established by different procedures
      that imply distinct forms of learning and memory, although the final result is
      analogous, i.e. avoidance of the gustatory stimulus associated with
      gastrointestinal discomfort. In fact, a double neurobiological system has been
      anatomically dissociated and, functionally, may be implicated in nausea and
      emesis, in food selection, and in neuroimmune interactions. Actually, a dual,
      parallel, and non-redundant gut-brain system has been proposed that sustain two
      different TAL modalities, concurrent and sequential. Concurrent TAL requires
      several trials and is inflexible, requiring simultaneity of the stimuli and the
      participation of the vagus nerve. In contrast, sequential TAL can be acquired in
      one trial and is flexible, permits long inter-stimulus delays, and is independent
      of vagal pathways. These two TAL modalities are analyzed in the light of the
      recent proposal that different acquisition processes are sustained by distinct
      cerebral systems.

PMID- 16084591
TI  - Lesions of structures showing FOS expression to cat presentation: effects on
      responsivity to a Cat, Cat odor, and nonpredator threat.
AB  - Exposure of rats to a cat elicits Fos activity in a number of brain areas or
      structures. Based on hodological relationships of these, Canteras has proposed a
      medial hypothalamic defense system, with input from several forebrain sites. Both
      electrolytic and neurotoxic lesions of the dorsal premammillary nucleus, which
      shows the strongest Fos response to cat exposure, produce striking decrements in
      a number of defensive behaviors to a cat or to cat odor stimuli, but do not have
      a major effect on either postshock freezing, or responsivity to the odor of a
      female in estrus. Neurotoxic lesions of the medial amygdala produce decrements in
      defensiveness to predator stimuli, particularly odor stimuli, that are consistent
      with a view of this structure as involved with allomonal cues. While dorsal
      hippocampal lesions had little effect on responsivity to predator stimuli,
      neurotoxic lesions of the ventral hippocampus reduced freezing and enhanced a
      variety of nondefensive behaviors to both cat odor and footshock, with similar
      reductions in defensiveness during context conditioning tests for cat odor, cat
      exposure and footshock. These results support the view that the dorsal
      premammillary nucleus is strongly and selectively involved in control of
      responsivity to predator stimuli. Structures with important input into the medial
      hypothalamic defense system appear also to be functionally involved with
      antipredator defensive behaviors, and these lesion studies may suggest specific
      hypotheses as to the particular defense functions of different areas.

PMID- 16084592
TI  - Ethological and temporal analyses of anxiety-like behavior: the elevated plus
      maze model 20 years on.
AB  - As well as being considered a reliable measurement instrument of animal anxiety
      like behavior, the elevated plus-maze (EPM) is also used as a post-hoc test to
      evaluate emotionality in genetically modified rodents. The present review
      considers factors which may further improve the validity
      (predictive/face/construct) of the EPM model: (1) the importance of measuring
      defensive patterns of response such as risk assessment in addition to traditional
      measures such as open arm time; (2) other methodological refinements such as min
      by-min scoring and use of a test/retest protocol; and (3) the identification and
      control of major sources of variability in this test. To estimate whether current
      use of the EPM by researchers takes the above factor into account, a survey of
      the recent literature was conducted. Results showed that the majority of studies
      have not yet assimilated these important considerations into their use of the
      EPM. For example, although risk assessment measures may be more sensitive to
      anxiety modulating drugs than traditional measures, only a quarter of studies
      have adopted them. It is hoped that this review can provide insights into the
      optimal use of the EPM, a simple task that can be very complex in terms of
      behavioral analysis.

PMID- 16084593
TI  - A homolog of the human chemokine receptor CXCR1 is expressed in the mouse.
AB  - Two distinct genes are present in the human genome encoding receptors for human
      interleukin-8 (hCXCL8), referred to as hCXCR1 and hCXCR2. While it seems clear
      that orthologous genes are present in the genomes of several mammals, the
      existence of a gene encoding an ortholog of hCXCR1 in the mouse has thus far been
      controversial. We have isolated a cDNA that is highly similar to the cDNAs of
      hCXCR1 and hCXCR2, but is clearly distinct from the cDNA encoding mouse CXCR2
      (mCXCR2). The encoded protein, designated mouse CXCR1-like (mCXCR1-like), shares
      64, 57, 57, and 89% identical amino acids with hCXCR1, hCXCR2, mCXCR2, and rCXCR1
      like, respectively. The gene encoding mCXCR1-like was mapped to mouse chromosome
      1 and its genomic organization was determined to be very similar to the
      organization of the gene encoding hCXCR1. Like hCXCR1, mCXCR1-like was found to
      be expressed at the mRNA level in neutrophils. In addition, mRNA encoding mCXCR1
      like was detected in liver, kidney, and spleen. In spleen, mCXCR1-like
      transcripts were predominantly found in CD4+ T cells. In liver, mCXCR1-like
      transcripts were identified in residual CD3+ T cells and macrophages, suggesting
      that mCXCR1-like may regulate inflammatory and immunological processes in the
      liver. When expressed as a recombinant protein, mCXCR1-like was not activated by
      a large panel of known CXC chemokines of human and murine origin. These findings
      suggest that a homolog or ortholog of hCXCR1 is expressed in the mouse to be
      activated by a hitherto unknown CXC chemokine of the mouse.

PMID- 16084594
TI  - Short-term oral exposure to aluminium decreases glutathione intestinal levels and
      changes enzyme activities involved in its metabolism.
AB  - To study the effects of aluminium (Al) on glutathione (GSH) metabolism in the
      small intestine, adult male Wistar rats were orally treated with AlCl3.6H2O at
      doses of 30, 60, 120 and 200 mg/kg body weight (b.w.) per day, during seven days.
      Controls received deionized water. At doses above 120 mg/kg b.w., Al produced
      both a significant reduction of GSH content and an increase of oxidized/reduced
      glutathione ratio (P < 0.05). The index of oxidative stress of the intestine
      mucosa in terms of lipid peroxidation evaluated by thiobarbituric acid reactive
      substances was significantly increased (52%) at higher Al dose used. The duodenal
      expression of the multidrug resistance-associated protein 2 in brush border
      membranes, determined by Western blot technique, was increased 2.7-fold in rats
      treated with 200mg AlCl3/kg b.w (P < 0.01). Intestine activities of both GSH
      synthase (from 60 mg/kg b.w.) and GSSG-reductase (from 120 mg/kg b.w.) were
      significantly reduced (26% and 31%, respectively) while glutathione-S-transferase
      showed to be slightly modified in the Al-treated groups. Conversely, gamma
      glutamyltranspeptidase activity was significantly increased (P < 0.05) due to the
      Al treatment. Al reduced in vitro mucosa-to-lumen GSH efflux (P < 0.05). A
      positive linear correlation between the intestine GSH depletion and reduction of
      in situ 45Ca intestinal absorption, both produced by Al, was found (r = 0.923, P
      = 0.038). Taking as a whole, these results show that Al would alter GSH
      metabolism in small intestine by decreasing its turnover, leading to an unbalance
      of redox state in the epithelial cells, thus contributing to deteriorate GSH
      dependent absorptive functions.

PMID- 16084595
TI  - Identification of complexes containing glutathione with As(III), Sb(III), Cd(II),
      Hg(II), Tl(I), Pb(II) or Bi(III) by electrospray ionization mass spectrometry.
AB  - Electrospray ionization mass spectrometry (ESI-MS) of mixtures containing
      glutathione (GSH) and nitrates, oxides or chlorides of the heavy metals, arsenic,
      antimony, cadmium, mercury, thallium, lead or bismuth allows for definitive
      identification of complexes in the gas phase. In the positive ion mode, spectra
      show prominent m/z peaks that are assigned to monocations of general formulae
      [E(GSH)-xH]+ (E = Cd, Hg, Tl, Pb, As, Sb or Bi; x = 0, 1 or 2), [E(GSH)2-xH]+ (E
      = Hg, As, Sb, or Bi; x = 1 or 2), [E(GSH)3-xH]+ (E = As, Sb or Bi; x = 2),
      [E2(GSH)-xH]+ (E = Tl or Pb; x = 1 or 3), [E2(GSH)2-xH]+ (E = Bi; x = 5),
      [E2(GSH)3-xH]+ (E = Bi; x = 5), and/or [E3(GSH)-xH]+ (E = Tl; x = 2). Spectra
      obtained in the negative ion mode give m/z peaks observed in assigned to
      monoanionic species that correspond to some of the monocationic species listed
      above with two protons removed. The results demonstrate the potential application
      of ESI-MS as a versatile and efficient approach to study toxic heavy metals in
      biological systems. In addition, the observations provide a foundation database
      to understand the chemistry of these heavy metals with bio-molecules.

PMID- 16084596
TI  - Reaction mechanisms of non-heme diiron hydroxylases characterized in whole cells.
AB  - Whole cells expressing the non-heme diiron hydroxylases AlkB and toluene 4
      monooxygenase (T4MO) were used to probe enzyme reaction mechanisms. AlkB
      catalyzes the hydroxylation of the radical clock substrates bicyclo[4.1.0]heptane
      (norcarane), spirooctane and 1,1-diethylcyclopropane, and does not catalyze the
      hydroxylation of the radical clocks 1,1-dimethylcyclopropane or 1,1,2,2
      tetramethylcyclopropane. The hydroxylation of norcarane yields a distribution of
      products consistent with an "oxygen-rebound" mechanism for the enzyme in both the
      wild type Pseudomonas putida GPo1 and AlkB from P. putida GPo1 expressed in
      Escherichia coli. Evidence for the presence of a substrate-based radical during
      the reaction mechanism is clear. With norcarane, the lifetime of that radical
      varies with experimental conditions. Experiments with higher substrate
      concentrations yield a shorter radical lifetime (approximately 1 ns), while
      experiments with lower substrate concentrations yield a longer radical lifetime
      (approximately 19 ns). Consistent results were obtained using either wild type or
      AlkB-equipped host organisms using either "resting cell" or "growing cell"
      approaches. T4MO expressed in E. coli also catalyzes the hydroxylation of
      norcarane with a radical lifetime of approximately 0.07 ns. No radical lifetime
      dependence on substrate concentration was seen. Results from experiments with
      diethylcyclopropane, spirooctane, dimethylcyclopropane, and diethylcyclopropane
      are consistent with a restricted active site for AlkB.

PMID- 16084598
TI  - Optimized protocols for the simultaneous preparation of primary neuronal cultures
      of the neocortex, hippocampus and cerebellum from individual newborn (P0.5)
      C57Bl/6J mice.
AB  - Knockout mouse models allow preparation of primary neuronal cultures from
      distinct brain regions in order to investigate the underlying neuronal
      pathomechanisms of human metabolic diseases associated with severe, regionally
      distinct brain pathologies (e.g. Zellweger syndrome, the most severe form of a
      peroxisomal biogenesis disorder). However, homozygous mouse pups with Zellweger
      syndrome usually die shortly after birth. Therefore, in this study, we
      established optimized protocols for the simultaneous preparation and cultivation
      of serum-free primary neuronal cultures from distinct brain regions (medial
      neocortex, hippocampus and cerebellum) from individual newborn (P0.5) C57Bl/6J
      mice. For each of the three types of neuronal cultures, we have optimized the
      isolation procedures and cultivation conditions including coating substrates,
      enzyme digestion, mode of trituration, seeding density and composition of the
      culture medium. As indicated by indirect immunofluorescence using antibodies
      against NeuN, GFAP and CNPase, the purity of the distinct neuronal cultures was
      high. The percentage of oligodendrocytes was less than 1% in all neuronal
      cultures. Only 5% astrocytes were present in cortical, 7% in hippocampal and 10%
      in cerebellar cultures. Cytosine arabinofuranoside (AraC) treatment reduced the
      percentage of astrocytes only significantly in hippocampal cultures, however,
      increased the percentage of apoptotic neurons in hippocampal and cortical
      cultures.

PMID- 16084599
TI  - An approach to pediatric brow dermoids: an upper eyelid crease incision.
AB  - Dermoids are common periorbital masses in children. Traditional surgical
      approaches have included direct incision over the mass, above, below or through
      the brow and parallel to the superior orbital rim, a Lynch incision, a lateral
      canthotomy or an upper eyelid crease and orbicularis oculi splitting incision. We
      report a case of a child with a lateral brow dermoid whose lesion was
      successfully removed via an upper eyelid crease approach that avoided an
      orbicularis oculi incision.

PMID- 16084600
TI  - Charcot-Marie-Tooth Disease type 1 and pediatric true vocal fold paralysis.
AB  - A case study of a child with Charcot-Marie-Tooth type 1 (CMT1) that presented
      with bilateral vocal fold paralysis. This is the first case of bilateral vocal
      fold paralysis in a child with CMT1 and it is the first case to be managed
      endoscopically. The surgical decision making process is discussed, and in
      particular the role of fiberoptic endoscopic evaluation of swallowing (FEES) in
      determining what surgical options should be entertained. In children with
      bilateral vocal fold paralysis who also have other neurologic abnormalities, the
      clinician should consider the possibility of CMT as the cause.

PMID- 16084601
TI  - Accidental choking in a patient with Treacher Collins syndrome.
AB  - A 3-year-old boy with Treacher Collins syndrome had undergone tracheostomy and
      placement of a secured cannula at the age of 4 months. When he was 3 years old,
      he manually extracted the secured cannula by himself and choked to death. Autopsy
      revealed upper airway obstruction with posterior deviation and mucosal
      hyperplasia of the radix linguae, mandibular hyperplasia, and occlusion of the
      artifical airway owing to intratracheal granuloma due to the long-standing
      tracheotomy. For safe, long-term use of a tracheostomy to maintain the airway,
      children with craniofacial abnormalities should be carefully supervised by their
      families to prevent accidental decannulation.

PMID- 16084602
TI  - AGS proteins: receptor-independent activators of G-protein signaling.
AB  - The identification of AGS proteins as receptor-independent activators of G
      protein signaling reveals unexpected mechanisms for the regulation of
      heterotrimeric G-protein activation and has opened up new areas of research
      related to the role of G proteins as signal transducers. In addition to their
      obvious interest associated with G-protein-coupled receptor signaling, AGS
      proteins might provide alternative binding partners for G-protein subunits that
      enable them to serve unexpected functions related to cell division,
      differentiation and organelle structure that might operate independently of a
      GPCR. Thus, these proteins and the concepts advanced with their discovery
      highlight the diversity associated with G-protein signaling and present new
      avenues for the development of therapeutics that target G-protein signaling.

PMID- 16084603
TI  - INGAP-related pentadecapeptide: its modulatory effect upon insulin secretion.
AB  - We examined the effects of a pentadecapeptide having the 104-118 aminoacid
      sequence of islet neogenesis-associated protein (INGAP-PP) on insulin secretion,
      and the morphological characteristics of adult and neonatal pancreatic rat islets
      cultured in RPMI and 10 mM glucose for 4 days, with or without different INGAP-PP
      concentrations (0.1-100 mug/ml). A scrambled 15 aminoacid peptide was used as
      control for the specificity of INGAP-PP effect. Cultured neonatal and adult
      islets released insulin in response to glucose (2.8-16.7 mM) in a dose-dependent
      manner, and to leucine and arginine (10 mM). In all cases, the response was
      greater in adult islets. INGAP-PP added to the culture medium significantly
      enhanced glucose- and aminoacid-induced insulin release in both adult and newborn
      rats; however, no changes were observed with the scrambled peptide. Similar
      results were obtained incubating freshly isolated adult rat islets with INGAP-PP.
      Whereas INGAP-PP did not induce significant changes in islet survival rate or
      proportion/number of islet cells, it increased significantly beta-cell size. This
      first demonstration of the enhancing effect of INGAP-PP on the beta-cell
      secretory response of adult and newborn islets opens a new avenue to study its
      production mechanism and potential use to increase the secretory capacity of
      endogenous islets in intact animals or of islets preserved for future
      transplants.

PMID- 16084604
TI  - Changes of the neuropeptides content and gene expression in spinal cord and
      dorsal root ganglion after noxious colorectal distension.
AB  - Visceral pain/hypersensitivity is a cardinal symptom of functional
      gastrointestinal disorders. With their peripheral and central (spinal)
      projections, sensory neurons in the dorsal root ganglia (DRG) are the "gateway"
      for painful signals emanating from both somatic and visceral structures. In
      contrast to somatic pain, the neurochemical pathways involved in visceral
      pain/hypersensitivity have not been well studied. We hypothesized the
      neuropeptide changes in spinal cord and DRG during visceral pain would mirror
      similar changes in somatic nociception. Noxious (painful) colorectal distension
      (CRD) was done by distending a rectal balloon up to 60 mm Hg phasically for 1 h
      in Sprague-Dawley rats. The spinal content of calcitonin gene-related peptide
      (CGRP), substance P (SP), galanin and vasoactive intestinal peptide (VIP) as well
      as their mRNAs in DRG were measured at 0, 4 and 24 h after the CRD. Visceromotor
      reflex (VMR) was measured by recording the electromyogram at the abdominal muscle
      in response to CRD. Distal colorectum was removed for evaluating the presence of
      inflammation. No significant evidence of histological inflammation was seen in
      the colonic mucosa/submucosa after repeated CRD, which is confirmed by
      myeloperoxidase assay. The spinal content of CGRP and SP decreased significantly
      4 h after CRD, while galanin and VIP levels increased gradually and reached
      highest level at 24 h (p<0.05). The mRNAs in DRG of the neuropeptides were
      significantly upregulated after CRD (p<0.05). VMR recording showed the rat's
      colon became hypersensitive 4 h after CRD, a sequence parallel to the spinal
      changes of CGRP and SP in timeframe. Noxious mechanical distension of the
      colorectum causes an acute change in the spinal levels of excitatory
      neurotransmitters (CGRP and SP), probably reflecting central release of these
      peptides from sensory neurons and contributing to the hypersensitivity following
      the noxious CRD. This is followed by a slower change in the levels of the
      inhibitory neurotransmitter galanin and VIP. Such stimulation results in
      significant alternation of the gene expression in DRG, reflecting the plasticity
      of the neuronal response. In the absence of visceral inflammation, the
      aforementioned neuropeptides are important mediators in the processing of
      visceral pain/hypersensitivity.

PMID- 16084605
TI  - GhHb1: a nonsymbiotic hemoglobin gene of cotton responsive to infection by
      Verticillium dahliae.
AB  - Verticillium wilt of cotton is a widespread and destructive disease that is
      caused by the fungus pathogen Verticillium dahliae. Although no cotton cultivar
      is immune to the disease, some genotypes exhibit superior wilt tolerance. To gain
      an insight into the molecular mechanisms responsible for wilt tolerance, we
      employed the method of suppression subtractive hybridization (SSH) to isolate
      genes whose expression is up-regulated after inoculation of the pathogen in a
      wilt-tolerant cotton cultivar (Gossypium hirsutum cv. BD18). Among the identified
      candidate ESTs, a cDNA representing a nonsymbiotic hemoglobin gene (designated
      GhHb1) was further characterized in this study. Northern blot hybridization
      demonstrated that GhHb1 shares similar characteristics to some other nonsymbiotic
      hemoglobin genes including the hypoxic stress-induced expression. Sub-cellular
      localization analysis indicated that GhHb1 proteins were predominantly present in
      the nucleus with a minor amount appearing in the cytoplasm. Two novel features of
      GhHb1 were also identified, indicating that GhHb1 expression is activated in the
      cotton roots after inoculation with V. dahliae and that exogenous hydrogen
      peroxide induces GhHb1 expression. These results suggest that the GhHb1 may play
      a role in the defense response of G. hirsutum against V. dahliae invasion.

PMID- 16084606
TI  - Identification and characterization of membralin, a novel tumor-associated gene,
      in ovarian carcinoma.
AB  - Identification of new genes in cancer is the key to understand the molecular
      basis of tumor development as well as provide potential diagnostic markers and
      therapeutic targets. A novel gene, membralin (GeneBank accession number:
      DQ005958), was cloned from a human ovarian cancer cell line. Human membralin is
      unique and does not share significant sequence homology with other human genes,
      only membralins of other species. The gene contains 11 exons which encode at
      least two spliced variants in human cancer. The long form of membralin (membralin
      1) comprises all 11 exons, encoding a protein of 620-amino acids long and the
      short form of membralin (membralin-3) contains all exons except for exon 10,
      encoding a protein of 408 amino acids. Expression of different membralin isoforms
      depends on tissue type. The long form, membralin-1, is expressed in ovarian and
      colorectal carcinomas but not in breast or pancreatic carcinomas, which express
      only the short splice form, membralin-3. Membralin-1-GFP fusion protein
      demonstrates exclusive cytoplasmic localization. Based on quantitative real-time
      PCR, in situ hybridization and Western blot analysis, membralin was highly
      expressed in ovarian serous carcinomas as compared to ovarian surface epithelium
      (P<0.001). Ovarian carcinomas in effusions demonstrated a significantly higher
      level of membralin expression than in solid tumors (P<0.001). In conclusion,
      these findings represent the first characterization of human membralin and
      suggest that membralin is a novel tumor-associated marker in ovarian serous
      carcinomas.

PMID- 16084607
TI  - VanabinP, a novel vanadium-binding protein in the blood plasma of an ascidian,
      Ascidia sydneiensis samea.
AB  - Some ascidians accumulate high levels of the transition metal vanadium in their
      blood cells. The process of vanadium accumulation has not yet been elucidated. In
      this report, we describe the isolation and cDNA cloning of a novel vanadium
      binding protein, designated as VanabinP, from the blood plasma of the vanadium
      rich ascidian, Ascidia sydneiensis samea. The predicted amino acid sequence of
      VanabinP was highly conserved and similar to those of other Vanabins. The N
      terminus of the mature form of VanabinP was rich in basic amino acid residues.
      VanabinP cDNA was originally isolated from blood cells, as were the other four
      Vanabins. However, Western blot analysis revealed that the VanabinP protein was
      localized to the blood plasma and was not detectable in blood cells. RT-PCR
      analysis and in situ hybridization indicated that the VanabinP gene was
      transcribed in some cell types localized to peripheral connective tissues of the
      alimentary canal, muscle, blood cells, and a portion of the branchial sac.
      Recombinant VanabinP bound a maximum of 13 vanadium(IV) ions per molecule with a
      Kd of 2.8 x 10(-5) M. These results suggest that VanabinP is produced in several
      types of cell, including blood cells, and is immediately secreted into the blood
      plasma where it functions as a vanadium(IV) carrier.

PMID- 16084608
TI  - OxLDL induced cell death is inhibited by the macrophage synthesised pterin, 7,8
      dihydroneopterin, in U937 cells but not THP-1 cells.
AB  - The atherosclerotic plaque is an inflammatory site where macrophage cells are
      exposed to cytotoxic oxidised low density lipoprotein (oxLDL). Interferon-gamma
      released from T-cells results in macrophage synthesis of 7,8-dihydroneopterin
      which has antioxidant and cytoprotective activity. Using the human derived
      monocyte-like U937 and THP-1 cell lines, we examined whether 7,8-dihydroneopterin
      could inhibit the cytotoxic effect of oxLDL. In U937 cells, oxLDL caused a
      dramatic loss of cellular glutathione and caspase independent cell death
      associated with phosphatidylserine exposure on the plasma membrane. 7,8
      Dihydroneopterin completely blocked the cytotoxic effect of oxLDL. In contrast,
      oxLDL initiated THP-1 cell apoptosis with reduction in cellular thiols, caspase-3
      activation and plasma membrane phosphatidylserine exposure. 7,8-Dihydroneopterin
      was unable to alter these processes or restore the THP-1 cellular thiol content.
      7,8-Dihydroneopterin did provide some protection to both THP-1 cells and U937
      cells from AAPH derived peroxyl radicals. The preincubation of oxLDL with 7,8
      dihydroneopterin did not reduce cytotoxicity, suggesting that 7,8
      dihydroneopterin may be acting in U937 cells by scavenging intracellular oxidants
      generated by the oxLDL. The data show that muM levels of 7,8-dihydroneopterin may
      prevent oxLDL mediated cellular death within atherosclerotic plaques.

PMID- 16084609
TI  - Age-related changes in postural responses to externally- and self-triggered
      continuous perturbations.
AB  - This is a cross sectional study of eight healthy young (age 22+/-2 years) and
      eight healthy older (age 70+/-5 years) adults who participated in an experiment
      in which they had to keep their balance while standing on a platform moving in
      the anterior/posterior direction. The 20 cm peak-to-peak platform movements were
      sinusoidal at increasing frequencies up to 0.61 Hz. The frequency increases were
      either sudden and unpredictable (externally-triggered perturbations) or
      controlled by the subjects themselves (self-triggered perturbations). To maintain
      balance, all subjects used anticipatory adjustments such as early postural muscle
      activation, leading to fewer steps being taken, tighter coupling of the center of
      pressure (COP) and the platform movements, and small COP excursions. These
      adjustments were found to be lacking for externally-triggered perturbations in
      older subjects; in these subjects the COP range was larger and more often in less
      safe regions at the boundaries of the base of support.

PMID- 16084610
TI  - The effect of oestrogen on megakaryocyte differentiation and platelet counts in
      vivo.
AB  - BACKGROUND: Oestrogen alters megakaryocyte number in humans and mice. In mice,
      high-dose oestrogen stimulates an initial increase in megakaryocyte number
      followed by a decrease. However, the cellular action, effect of physiologically
      circulating and smaller supra-physiological oestrogen doses and whether changes
      in megakaryocyte number alter platelet counts have not been studied. METHODS: To
      further examine oestrogen's effect on megakaryocytes and platelets we
      administered intact or ovariectomised mice various doses of oestrogen and
      measured megakaryocyte and platelet counts. To determine the cellular mechanism
      by which oestrogen influences megakaryocytopoesis we also examined its effect on
      markers of megakaryocytic differentiation (CD41, CD61, CD34). RESULTS: We found
      that large doses of oestrogen (500 microg/kg) increased mature CD41+
      megakaryocyte number within 2 days, and this was associated with an increase in
      circulating platelets. Smaller supra-physiological doses (100 microg/kg) lacked
      this anabolic effect, but still suppressed megakaryocyte and platelet number by
      day 10 in intact and ovariectomised mice. This was preceded by a reduction in the
      number of CD61+ megakaryoblasts and CD34+ precursors available to form mature
      megakaryocytes. In contrast, ovariectomy had no effect on megakaryocyte or
      platelet number, indicating that circulating oestrogen concentrations do not
      influence megakaryocyte differentiation or activity. CONCLUSIONS: Our data
      suggest that in mice at least platelet counts reflect changes in megakaryocyte
      number, and while both are independent of physiological hormone concentrations,
      they are sensitive to even small supra-physiological doses of oestrogen.
      Therefore, to ovoid disrupting platelet homeostasis the dose of oestrogen given
      should be no more than replacement.

PMID- 16084611
TI  - Filter no reflow during percutaneous coronary interventions using the Filterwire
      distal protection device.
AB  - BACKGROUND: Distal protection devices are increasingly used to prevent
      embolization during percutaneous coronary interventions (PCI) in saphenous vein
      grafts (SVG) and native coronary arteries (NV). During interventions with the
      Filterwire device we have observed reduced flow that is reversible following
      removal of the filter (filter no reflow, FNR), which might be erroneously
      interpreted as true no reflow and might be associated with reduced capture
      efficiency of the basket. METHODS: We analyzed the incidence of FNR in 58
      patients (60 lesions) at high risk of embolization undergoing PCI of either a SVG
      or a NV using the Filterwire (Boston Scientific, Natick, MA). Qualitative and
      quantitative angiographic analysis was performed, and the volume of collected
      debris was estimated using a photographic technique. RESULTS: In our population,
      about 1/3 of the cases showed FNR, which was associated with angiographically
      visible filling defects within the basket, indicating macroembolism. However some
      patients (especially those undergoing vein graft interventions) showed filling
      defects without FNR, and some others FNR without filling defects. Thus we tried
      to understand the predictors of FNR: FNR was associated with higher amount of
      collected debris (36.97 +/- 42.98 mm(3) vs. 11.31 +/- 18.47 mm(3), p = 0.005),
      was neither prevented by abciximab, nor predicted by high thrombotic burden,
      increasing stent volume or need for predilatation. When patient with and without
      angiographically evident macroembolisation were separately analyzed, a linear
      correlation of FNR with the quantity of debris was only apparent in the
      macroembolization group. CONCLUSIONS: Interventionalists should be aware of the
      "Filter No Reflow", a common but reversible angiographic complication when the
      Filterwire device is used. Reduced flow seen during these procedures should be
      treated conservatively. Mechanical obstruction of the filter, but also other
      mechanisms (pharmacologically active debris? platelet aggregates?) play a role in
      this phenomenon.

PMID- 16084614
TI  - Rapid identification of Mycobacterium species by lectin agglutination.
AB  - The purpose of the present study is to explore the possibility that plant lectins
      can be used for the development of rapid and inexpensive technique for
      differentiation of mycobacterial species. The method is based on interaction
      between mycobacteria and lectins as visualized by agglutination in a microtiter
      plate. We employed 18 mycobacterium species and determined the minimal lectin
      concentration (MLC) of 23 different lectins. For some of the bacteria as a high
      as 1000 microg/ml of one or more lectins were required to induce agglutination,
      while for other strains as low as 1.95 microg/ml of the lectin were needed. A
      unique pattern of agglutination was observed for each species over a range of 62
      1000 microg/ml lectin concentrations. There were little or no variations in MLC
      within strains (intraspecies) of each of two species tested. In contrast, there
      were marked interspecies variations in MLC. Analysis of the MLC showed that the
      highest score of interspecies differences with 23 lectins was obtained at 125
      microg/ml lectin concentration. At this concentration it was found that the
      pattern of agglutinations with only two lectins was sufficient to differentiate
      mycobacterium species from each other. Because the bacteria-lectin interaction is
      adaptable to various methods of visualization, our findings may set the stage for
      developing a rapid and reliable tool to differentiate mycobacterium species.

PMID- 16084615
TI  - Towards the preparative and large-scale precision manufacture of virus-like
      particles.
AB  - Virus-like particles (VLPs) are of interest in vaccination, gene therapy and drug
      delivery, but their potential has yet to be fully realized. This is because
      existing laboratory processes, when scaled, do not easily give a compositionally
      and architecturally consistent product. Research suggests that new process routes
      might ultimately be based on chemical processing by self-assembly, involving the
      precision manufacture of precursor capsomeres followed by in vitro VLP self
      assembly and scale-up to required levels. A synergistic interaction of
      biomolecular design and bioprocess engineering (i.e. biomolecular engineering) is
      required if these alternative process routes and, thus, the promise of new VLP
      products, are to be realized.

PMID- 16084616
TI  - The effect of learning condition on perceptual anticipation, awareness, and
      visual search.
AB  - The efficacy of explicit and implicit learning paradigms was examined during the
      very early stages of learning the perceptual-motor anticipation task of
      predicting ball direction from temporally occluded footage of soccer penalty
      kicks. In addition, the effect of instructional condition on point-of-gaze during
      learning was examined. A significant improvement in horizontal prediction
      accuracy was observed in the explicit learning group; however, similar
      improvement was evident in a placebo group who watched footage of soccer matches.
      Only the explicit learning intervention resulted in changes in eye movement
      behaviour and increased awareness of relevant postural cues. Results are
      discussed in terms of methodological and practical issues regarding the
      employment of implicit perceptual training interventions.

PMID- 16084617
TI  - Motor control and learning: a contribution from the European College of Sport
      Science.

PMID- 16084618
TI  - A survey of glycosidase activities of commercial wine strains of Oenococcus oeni.
AB  - Lactic acid bacteria play an important role in wine-making by undertaking the
      malolactic fermentation, yet little information is available on other aspects of
      their physiology, such as their profile of external enzymatic activities. In this
      study we sought evidence for the existence and action of glycosidase enzymes in
      wine isolates of Oenococcus oeni. This group of enzymes is of interest because of
      their potential for liberation of grape-derived aroma compounds from their
      natural glycosylated state. This comprehensive study reveals that these bacteria
      produce glycosidases that might be important in wine-making. Strains did not
      necessarily hydrolyse all substrates tested, but rather were grouped according to
      substrate specificity. Thus a subset comprising strains 2, 5 and 16 possessed
      high cumulative activities against beta-d- and alpha-d-glucopyranoside
      substrates, while a group comprising strains 4, 21 and 22 was noted for superior
      hydrolysis of beta-d-xylopyranoside, alpha-l-rhamnopyranoside and alpha-l
      arabinofuranoside substrates. Key physico-chemical inhibitors of analogous
      systems from other microorganisms were seen to produce variable responses across
      the strains investigated here. Accordingly, several strains retained significant
      hydrolytic activity at typical wine pH values ( approximately 3.0-4.0), residual
      glucose and fructose contents (up to 20 g/L), and ethanol contents (up to 12%).
      These findings highlight the potential of O. oeni as a useful alternative source
      of glycosidase enzymes for use in wine-making.

PMID- 16084619
TI  - Effect of transglutaminase treatment on the properties of cast films of soy
      protein isolates.
AB  - The objective of this work was to investigate the effect of microbial
      transglutaminase (MTGase) treatment on the properties and microstructures of soy
      protein isolate (SPI) films cast with 0.6 plasticizer per SPI (gg(-1)) of
      glycerol, sorbitol and 1:1 mixture of glycerol and sorbitol, respectively.
      Tensile strength (TS), elongation at break (EB), water vapor transmission rate
      (WVTR) or water vapor permeability (WVP), moisture content (MC), total soluble
      matter (TSM), lipid barrier property and surface hydrophobicity of control and
      MTGase-treated films were evaluated after conditioning film specimens at 25
      degrees C and 50% relative humidity (RH) for 48 h. The treatment by 4 units per
      SPI (Ug(-1)) of MTGase increased the TS and surface hydrophobicity by 10-20% and
      17-56%, respectively, and simultaneously significantly (P< or =0.05) decreased
      the E, MC and transparency. The WVTR or TSM of SPI films seemed to be not
      significantly affected by enzymatic treatment (P>0.05). The MTGase treatment also
      slowed down the moisture loss rate of film-forming solutions with various
      plasticizers during the drying process, which was consistent with the increase of
      surface hydrophobicity of SPI films. Microstructural analyses indicated that the
      MTGase-treated films of SPI had a rougher surface and more homogeneous or compact
      cross-section compared to the controls. These results suggested that the MTGase
      treatment of film-forming solutions of SPI prior to casting could greatly modify
      the properties and microstructures of SPI films.

PMID- 16084620
TI  - Construction of cellobiose-growing and fermenting Saccharomyces cerevisiae
      strains.
AB  - Beta-glucosidase genes of fungal origins were isolated and heterologously
      expressed in Saccharomyces cerevisiae to enable growth on the disaccharide,
      cellobiose. To promote secretion of the beta-glucosidases, the genes were fused
      to the secretion signal of the Trichoderma reesei xyn2 gene and constitutively
      expressed from a multi-copy yeast expression vector under transcriptional control
      of the S. cerevisiae PGK1 promoter and terminator. The resulting recombinant
      enzymes were characterized with respect to pH and temperature optimum, as well as
      kinetic properties. The two most promising enzymes, BGL1 from Saccharomycopsis
      fibuligera and BglA from Aspergillus kawachii, were anchored to the yeast cell
      surface by fusing the mature proteins to the alpha-agglutinin (AGalpha1) or cell
      wall protein 2 (Cwp2) peptides. The maximum specific growth rates (mu(max)) of
      the recombinant S. cerevisiae strains were determined in batch cultivation. S.
      cerevisiae secreting the recombinant S. fibuligera BGL1 enzyme sustained growth
      aerobically and anaerobically, in minimal medium containing 5g L(-1) cellobiose
      at 0.23 h(-1) (compared to 0.29 h(-1) on glucose) and 0.18 h(-1) (compared to
      0.25 h(-1) on glucose), respectively. Substrate consumption and product formation
      were determined to evaluate product yields in glucose and cellobiose.

PMID- 16084621
TI  - Purification and characterization of an L-arabinose isomerase from an isolated
      strain of Geobacillus thermodenitrificans producing D-tagatose.
AB  - The araA gene, encoding l-arabinose isomerase (AI), from the thermophilic
      bacterium Geobacillus thermodenitrificans was cloned and expressed in Escherichia
      coli. Recombinant AI was isolated with a final purity of about 97% and a final
      specific activity of 2.10 U/mg. The molecular mass of the purified AI was
      estimated to be about 230 kDa to be a tetramer composed of identical subunits.
      The AI exhibited maximum activity at 70 degrees C and pH 8.5 in the presence of
      Mn2+. The enzyme was stable at temperatures below 60 degrees C and within the pH
      range 7.5-8.0. d-Galactose and l-arabinose as substrate were isomerized with high
      activities. Ribitol was the strongest competitive inhibitor of AI with a Ki of
      5.5mM. The apparent Km and Vmax for L-arabinose were 142 mM and 86 U/mg,
      respectively, whereas those for d-galactose were 408 mM and 6.9 U/mg,
      respectively. The catalytic efficiency (kcat/Km) was 48 mM(-1)min(-1) for L
      arabinose and 0.5mM(-1)min(-1) for D-galactose. Mn2+ was a competitive activator
      and increased the thermal stability of the AI. The D-tagatose yield produced by
      AI from d-galactose was 46% without the addition of Mn2+ and 48% with Mn2+ after
      300 min at 65 degrees C.

PMID- 16084622
TI  - HCV clearance and treatment outcome in genotype 1 HCV-monoinfected, HIV
      coinfected and liver transplanted patients on peg-IFN-alpha-2b/ribavirin.
AB  - BACKGROUND/AIMS: Differences in HCV-RNA clearance during therapy might explain
      the lower efficacy of peg-IFN/RBV in HIV/HCV-coinfection. There are limited data
      on HCV-RNA clearance and treatment outcomes in liver transplanted (LT) patients.
      METHODS: To assess the rates of SVR and baseline predictors of failure after 48
      weeks of weight-adjusted peg-IFN-alpha-2b/RBV in 120 patients with HCV genotype
      1: 61 HCV-monoinfected, 40 HIV-coinfected and 19 LT-patients. Viral clearance was
      evaluated in patients completing 24 weeks of therapy (n=112, 93%). RESULTS: SVR
      was significantly lower in HIV-coinfection than in HCV-monoinfection or LT (18
      vs. 39 vs. 42%, P<0.02). By multivariate analysis, HIV-coinfection (OR 3.048, 95%
      CI 1.133-8.196; P=0.027), baseline HCV-RNA over 800,000 IU/ml (OR 2.800; 95% CI
      1.121-6.993, P=0.027) and higher AST values (OR 1.009; 95% CI 1.001-1.018;
      P=0.028) were significantly associated to failure. Despite similar baseline HCV
      load (5.67 vs. 5.75 vs. 5.90 log10 IU/ml), HIV-coinfection showed significantly
      lower HCV-RNA decreases than HCV-monoinfection at weeks 4 (P=0.015), 12 (P=0.015)
      and 24 (P=0.0003), and than LT at weeks 12 (P=0.003) and 24 (P=0.023). 36/60
      subjects (60%) reaching EVR by week 12 obtained SVR vs. 3/60 (5%) who did not.
      CONCLUSIONS: HIV-coinfection was independently associated to treatment failure,
      and led to a significantly slower HCV-RNA clearance.

PMID- 16084623
TI  - Non-mammalian c-integrases are encoded by giant transposable elements.

PMID- 16084624
TI  - Identification of novel differentially expressed genes in human astrocytomas by
      cDNA representational difference analysis.
AB  - Diffuse infiltrating gliomas are the most common tumors of the central nervous
      system (CNS), naturally progressing from a lower-grade to a higher-grade
      malignancy. Several genetic alterations have been correlated with astrocytic
      tumors; however, a number of as yet unknown genes may also be involved.
      Therefore, we set out to search for genes that are differentially expressed in
      anaplastic astrocytoma and normal CNS tissue by applying a PCR-based subtractive
      hybridization approach, namely, representational difference analysis (RDA). The
      results of DNA sequencing of a sample (96 cDNA clones) from the subtracted
      library allowed the identification of 18 different genes, some of which were
      represented by several cDNA clones, coding for the Np95, LMO1, FCGBP, DSCAM, and
      taxilin proteins. Quantitative real-time PCR analysis for five of these genes was
      performed using samples of astrocytic tumors of different grades, confirming
      their higher expression when compared to non-tumoral CNS tissue. Identification
      of differentially expressed genes present in gliomas but not in normal CNS tissue
      is important not only to better understand the molecular basis of these cancers,
      but also to generate diagnostic DNA chips, which may be useful in future
      therapeutic intervention.

PMID- 16084626
TI  - Inhibition of secretory phospholipase A2. 1-design, synthesis and structure
      activity relationship studies starting from 4-tetradecyloxybenzamidine to obtain
      specific inhibitors of group II sPLA2s.
AB  - Starting from 4-tetradecyloxybenzamidine (PMS815), a non-specific inhibitor of GI
      and GII PLA2s, we report in this work the discovery of the specificity through
      design, synthesis and structure-activity relationships studies of different kinds
      of PMS815 derivatives. The leading compound, 4,5-dihydro-3-(4
      tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one (9b, PMS1062) exhibits a micromolar
      IC50 towards three group II PLA2s, while inactive towards four group I and one
      group III enzymes in two in vitro enzymatic assay conditions. It is also able to
      block the PLA2-II activities induced by LPS and IL-6 in HepG2 cell line and no
      cytotoxicity is observed when PMS1062 is tested up to a concentration of 100
      microM in two different cell lines (A549 and LLC-PK1).

PMID- 16084627
TI  - [Scurvy as the outcome of a serious abnormal diet behaviour].

PMID- 16084628
TI  - [Plasma exchanges as treatment of severe acute immune thrombocytopenic purpura].
AB  - INTRODUCTION: High dose steroids and intravenous immunoglobulins are the gold
      treatment of acute immune thrombocytopenic purpura, before splenectomy for severe
      and refractory forms of the disease. Authors report two cases of severe acute
      refractory immune thombocytopenia with a dramatic response to plasma exchanges.
      EXEGESIS: The first case was an idiopathic form, complicated by hemorragic
      peritoneal effusion. After failure of steroids, intravenous immunoglobulins and
      splenectomy and 2 courses of rituximab, plasmapheresis normalized in 3 days
      platelet count. In the second observation, ITP was associated to systemic lupus
      with antiphospholipids antibodies and multivisceral failure, despite steroids and
      intravenous immunoglobulins. After 3 plasma exchanges, platelet count was
      normalized, and the patient is under remission after 24 months follow-up.
      CONCLUSION: Plasmapheresis must be evaluated as an emergency treatment in
      refractory forms of acute immune thrombocytopenic purpura.

PMID- 16084629
TI  - Credentials of Spirulina diet on stability and flux related properties on the
      biomineralization process during oxalate mediated renal calcification in rats.
AB  - BACKGROUND: High Spirulina diet is a potential risk factor for nephrolithiasis
      since it has the capacity to increase urinary oxalate and uric acid level,
      facilitating lithogenesis. Our aim was to identify the effect of Spirulina diet
      during hyperoxaluric condition in Wistar albino rats. METHODS: The animals were
      divided into four groups: control (Gl, n=6); ethylene glycol (EG) induced (G2,
      n=6); EG+Spirulina (G3, n=6); Spirulina alone (G4, n=6). EG at 0.75% was
      administered to G2 and G3 through drinking water for 4 weeks and Spirulina 1500
      mg/kg feed was administered to G3 and G4. RESULTS: Urinary parameters like
      oxalate, uric acid, calcium, urea, and creatinine (P<0.001) were found increased
      after Spirulina diet under hyperoxaluric conditions compared to the same without
      Spirulina diet. Similarly the BUN, plasma contents of uric acid, urea, creatinine
      (P<0.001) were found to be raised in G3. The renal and RBC GSH levels, as
      estimated by HPLC, seemed decreased when compared to G2. CONCLUSIONS: The present
      study shows that free radicals aid in the progression of nephrolithiasis. The
      crystal deposition was found to be high in the renal cells of G3 than G2 and TEM
      revealed damage in renal cell of G3 implying that the disease deteriorates by
      free radical injury. In contrast the Spirulina diet alone (G4) did not induce any
      features relating to stone forming condition suggesting that free radical release
      might have been suppressed due to enrichment of dietary antioxidants and
      vitamins. Thus the present investigation demonstrates that during hyperoxaluric
      conditions the Spirulina diet must possibly be avoided and can be considered in
      normal subjects checked for family history of renal stone deposition.

PMID- 16084630
TI  - B. Zinka et al., Unexplained cases of sudden infant death shortly after
      hexavalent vaccination.

PMID- 16084631
TI  - Myositis ossificans traumatica of the thenar region.
AB  - Myositis ossificans of the hand is extremely rare. We report an unusual case of
      myositis ossificans of the thenar muscles and discuss the diagnostic pitfalls
      whereby this condition can be mistaken for malignancy or infection.

PMID- 16084632
TI  - Trying to recollect past events: confidence, beliefs, and memories.
AB  - Numerous studies claim to have shown that false memories can be easily created in
      the laboratory. However, a critical analysis of the methods employed in these
      studies indicates that many of them do not address memory in the strict sense of
      the word. Instead, some of these studies assess the confidence that participants
      have in a fictitious (childhood) event, while others pertain to false beliefs
      about childhood events. While it is difficult to draw precise demarcation lines,
      we argue that inflated confidence, false beliefs, and false memories are
      different phenomena. Keeping the origins of these studies in mind (i.e., people
      who file lawsuits on the basis of their recovered memories), we propose that a
      fruitful, but stringent definition of false memories would incorporate their
      consequences. Thus, we argue that this research domain would profit from studies
      looking explicitly at whether experimental manipulations intended to implant
      false memories have overt behavioral consequences.

PMID- 16084633
TI  - Depression and mental health visits to physicians--a prospective records-based
      study.
AB  - Previous studies of access to care for depression have been based on cross
      sectional surveys of self-reported use of mental health service use. As the
      recall of use may be differentially biased by mood states, inferences about how
      well persons with depression are accessing services in comparison to other groups
      may be misleading. Accordingly, we estimated the magnitude of the depression-use
      associations in relation to key covariates based on prospective records of mental
      health visits to physicians. The sample, N = 23,063, of persons 12 years and
      older, was drawn from the 1996/97 Ontario Health Survey and linked to their
      administrative mental health care records 24 months forward in time. We found
      that depression-use associations were in the expected direction but similar in
      magnitude to associations for gender and education unlike previous self-reported
      use surveys. Female gender was positively related to the use of a primary care
      physician but negatively related to seeing a psychiatrist as opposed to a primary
      care physician. Those who had attained higher levels of education were more
      likely to be seen by physicians than those with lower education levels. The
      meaning behind these findings bears further study as it may have implications for
      primary care reform and the design of future studies of access.

PMID- 16084634
TI  - A socially neutral disease? Individual social class, household wealth and
      mortality from Spanish influenza in two socially contrasting parishes in
      Kristiania 1918-19.
AB  - The Spanish influenza pandemic of 1918-19 was one of the most devastating
      diseases in history, killing perhaps as many as 50-100 million people worldwide.
      Much of the literature since 1918 has favored the view that mortality from
      Spanish influenza was class neutral. This view has prevailed, even though several
      contemporary surveys showed that there indeed were clear differences between the
      classes in disease incidence and that case fatality rates from influenza and
      pneumonia also varied according to socioeconomic status. Furthermore, studies of
      more recent influenza epidemics have also shown that there can be clear class
      differentials in mortality in this type of illness--is there any reason to
      believe that Spanish influenza was different? This paper is the first study in
      which individual- and household-level data which are unique for the period are
      utilized to test the conservative hypothesis that Spanish influenza was a
      socially neutral disease with respect to mortality. Through the use of Cox
      regressions in an analysis of two socially contrasting parishes in the Norwegian
      capital city of Kristiania, it is shown that apartment size as an indicator of
      wealth of a household, in addition to social status of place of residence, were
      the only socioeconomic variables that had an independent and significant effect
      on mortality after controlling for age, sex and marital status.

PMID- 16084635
TI  - Caffeine and amphetamine produce cross-sensitization to nicotine-induced
      locomotor activity in mice.
AB  - Sensitization development is linked to the addictive potential of the drugs. The
      same mechanisms might play a role in sensitization development to the different
      addictive drugs. The aim of the study was to investigate the development of cross
      sensitization to caffeine and amphetamine in nicotine-induced locomotor
      sensitization in mice. Caffeine (2.5-20 mg/kg), amphetamine (1-16 mg/kg) or
      saline were injected to Swiss-Webster mice and locomotor activity was recorded
      for 30 min. Nicotine (0.5-2 mg/kg) or saline were injected to mice and locomotor
      activity was recorded for 30 min. Process was applied for 19 days, every other
      day (10 sessions). Caffeine (5 mg/kg), amphetamine (4 mg/kg) or saline were
      challenged to the different groups of nicotine-sensitized mice 2 days later on
      the last nicotine injection, and locomotor activity was recorded. Repetitive
      injections of nicotine (0.5-2 mg) produced locomotor sensitization in mice. After
      caffeine and amphetamine challenge injections, locomotor activity of the nicotine
      sensitized mice was found to be significantly higher than saline-pretreated mice.
      Saline challenge did not produce any significant effect in nicotine- or saline
      pretreated mice. Our results suggest that a cross-sensitization developed to both
      caffeine and amphetamine in nicotine-sensitized mice. In conclusion, similar
      central mechanisms may be responsible for the development of addiction to these
      substances.

PMID- 16084636
TI  - A 24-month dietary carcinogenicity study of DAG in mice.
AB  - This study evaluated the possible carcinogenic effects of DAG (diacylglycerol)
      oil when given in the diet at levels up to 6.0% for 24 months to mice. Dietary
      fat was provided by DAG and/or the control article, TG (triacylglycerol oil).
      Dietary concentrations (% DAG/% TG) were 0%/6.0% (TG control), 1.5%/4.5%,
      3.0%/3.0%, and 6.0%/0%. An additional control group received the standard rodent
      diet (fat content 4.5%). The clinical condition of the animals, ophthalmic
      findings, palpable mass occurrence, body weights and gross and histopathologic
      findings were unaffected by DAG in comparison to TG. The findings in DAG-treated
      groups were no different than those observed in the TG control group. The
      standard basal diet had 4.5% fat content. Both TG and/or DAG, when presented
      separately or together in the diet at a total fat level of 6.0%, resulted in some
      differences relative to the basal diet control (lower survival, higher body
      weights, lower food consumption, and higher incidences of macroscopic and
      microscopic findings), presumably related to the higher dietary fat content
      and/or the semi-purified diet. However, these parameters were similar in groups
      fed a diet with 6.0% dietary fat that was either DAG or TG. Thus, DAG at dietary
      concentrations up to 6.0% for 24 months produced no signs of systemic toxicity
      and had no effect on the incidence of neoplastic findings.

PMID- 16084637
TI  - Results of a 90-day safety assurance study with rats fed grain from corn rootworm
      protected corn.
AB  - The results of a 90-day rat feeding study with YieldGard (YieldGard Rootworm Corn
      is a registered trademark of Monsanto Technology, LLC.) Rootworm corn (MON 863)
      grain that is protected against feeding damage caused by corn rootworm larvae are
      presented. Corn rootworm-protection was accomplished through the introduction of
      a cry3Bb1 coding sequence into the corn genome for in planta production of a
      modified Cry3Bb1 protein from Bacillus thuringiensis. Grain from MON 863 and its
      near isogenic control were separately formulated into rodent diets at levels of
      11% and 33% (w/w) by Purina Mills, Inc. Additionally, six groups of rats were fed
      diets containing grain from different conventional (non-biotechnology-derived)
      reference varieties. The responses of rats fed diets containing MON 863 were
      compared to those of rats fed grain from conventional corn varieties. All diets
      were nutritionally balanced and conformed to Purina Mills, Inc. specifications
      for Certified LabDiet 5002. There were a total of 400 rats in the study divided
      into 10 groups of 20 rats/sex/group. Overall health, body weight gain, food
      consumption, clinical pathology parameters (hematology, blood chemistry,
      urinalysis), organ weights, gross and microscopic appearance of tissues were
      comparable between groups fed diets containing MON 863 and conventional corn
      varieties. This study complements extensive agronomic, compositional and farm
      animal feeding studies with MON 863 grain, confirming that it is as safe and
      nutritious as existing conventional corn varieties.

PMID- 16084638
TI  - A chronic dietary toxicity study of DAG (diacylglycerol) in Beagle dogs.
AB  - The potential chronic toxic effects of DAG (diacylglycerol) when administered
      orally for 12 months were evaluated in this dietary study in Beagle dogs. DAG is
      a cooking oil which contains >80% diglycerides, <20% triglycerides and 5%
      monoglycerides. For this study, a special diet was prepared with no dietary fat
      so that all of the dietary fat could be provided by DAG, at various
      concentrations together with a control oil. The control oil, TG
      (triacylglycerol), was prepared to contain >85% triglycerides, <10% diglycerides
      and 5% monoglycerides. The fatty acid composition for DAG and TG was closely
      matched. Dietary concentrations of 0% DAG/9.5% TG (TG control), 1.5% DAG/8.0% TG,
      5.5% DAG/4.0% TG, and 9.5% DAG/0% TG were presented daily, seven days per week,
      for 52 weeks. A second concurrent control group received the standard basal diet
      (Certified Canine LabDiet 5007, which has a fat content of 9.5%). The basal diet,
      control article-treated and DAG-treated groups each consisted of four male and
      four female dogs. Treatment was initiated in prejuvenile (2.5-month-old) dogs.
      Statistical evaluations compared the DAG-treated groups both to the basal diet
      and 9.5% TG control groups. The clinical condition of the animals, body weights,
      body weight gains and food consumption were unaffected by DAG. Hematology and
      urinalysis parameters were unaffected. No serum chemistry changes indicative of a
      toxic effect were observed. There were no effects noted on ECG data. No test
      article-related gross or histopathologic findings or changes in organ weights
      were observed. While there were no identifiable differences between the effects
      of TG and DAG, both caused some differences relative to the basal diet (lower
      food consumption, higher alkaline phosphatase, cholesterol and triglycerides).
      These differences were not toxicologically significant and were attributed to the
      differences in the diet rather than the fat source. Thus, DAG at dietary
      concentrations up to 9.5% for one year had no effect on normal canine growth and
      development, in comparison to TG.

PMID- 16084639
TI  - A 24-month dietary carcinogenicity study of DAG (diacylglycerol) in rats.
AB  - Toxicologic and carcinogenic effects of DAG (diacylglycerol) oil, administered in
      diet for 24 months to Crl:CD((R))(SD)-IGS BR rats, were evaluated using diet
      restricted and ad libitum-fed groups. All dietary fat (consistently 5.5%) was
      provided by DAG and/or the control article, TG (triacylglycerol) oil. Dietary
      concentrations (% DAG/% TG) were 0%/5.5%, 1%/4.5%, 2.75%/2.75% and 5.5%/0%.
      Separate groups were fed the 0%/5.5% and 5.5%/0% diets ad libitum. Another group
      received the standard rodent diet (fat content 4.5%) on the restricted feeding
      regimen. Clinical condition, ophthalmic findings, palpable mass occurrence, body
      composition, clinical pathology parameters and incidence of neoplastic lesions
      were unaffected by DAG in comparison to TG. Groups fed the 5.5% (DAG and/or TG)
      fat diet when compared to the 4.5% fat diet group displayed lower survival,
      higher body weights, organ weights, percent body fat, higher fat-related serum
      chemistry parameters, incidence of microscopic changes in the heart, kidneys,
      liver, bone marrow, spleen, and incidences of pituitary and mammary gland
      neoplasms. Parameters more affected in all the ad libitum groups than in the
      restricted diet groups (regardless of test article) fed the same diet included
      survival, body weights, body fat, fat-related serum chemistry parameters, and
      incidences of heart, kidney and liver microscopic changes. However, the DAG and
      TG ad libitum-fed groups were not different from one another. Thus, DAG-treated
      animals had no higher risk of carcinogenic effects than rats fed on similar
      feeding regimens with a diet in which all dietary fat came from TG.

PMID- 16084640
TI  - Fe(3+)-eta(2)-peroxo species in superoxide reductase from Treponema pallidum.
      Comparison with Desulfoarculus baarsii.
AB  - Superoxide reductases (SORs) are superoxide (O2-)-detoxifying enzymes that
      catalyse the reduction of O2- into hydrogen peroxide. Three different classes of
      SOR have been reported on the basis of the presence or not of an additional N
      terminal domain. They all share a similar active site, with an unusual non-heme
      Fe atom coordinated by four equatorial histidines and one axial cysteine
      residues. Crucial catalytic reaction intermediates of SOR are purported to be
      Fe(3+)-(hydro)peroxo species. Using resonance Raman spectroscopy, we compared the
      vibrational properties of the Fe3+ active site of two different classes of SOR,
      from Desulfoarculus baarsii and Treponema pallidum, along with their ferrocyanide
      and their peroxo complexes. In both species, rapid treatment with H2O2 results in
      the stabilization of a side-on high spin Fe(3+)-(eta(2)-OO) peroxo species.
      Comparison of these two peroxo species reveals significant differences in
      vibrational frequencies and bond strengths of the Fe-O2 (weaker) and O-O
      (stronger) bonds for the T. pallidum enzyme. Thus, the two peroxo adducts in
      these two SORs have different stabilities which are also seen to be correlated
      with differences in the Fe-S coordination strengths as gauged by the Fe-S
      vibrational frequencies. This was interpreted from structural variations in the
      two active sites, resulting in differences in the electron donating properties of
      the trans cysteine ligand. Our results suggest that the structural differences
      observed in the active site of different classes of SORs should be a determining
      factor for the rate of release of the iron-peroxo intermediate during enzymatic
      turnover.

PMID- 16084641
TI  - A 2-year follow-up study of alcohol consumption and risk of dementia.
AB  - BACKGROUND: This report focused on investigating the relationship between alcohol
      consumption and dementia in elderly people through prospective studies. METHODS:
      We conducted a 2-year follow-up study of elderly people from six communities in
      Chongqing, China. Dementia was detected using the Mini-Mental State Examination
      (MMSE) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R).
      The relationship between alcohol consumption and dementia was investigated using
      multiple logistic regression models, adjusting for the potential confounders age,
      sex, educational level and cigarette smoking. RESULTS: Light-to-moderate drinking
      was associated with a significantly lower risk of dementia compared with non
      drinking. Excessive drinking was related to a higher risk of dementia. The effect
      of light-to-moderate drinking seemed most prominent among vascular dementia, 0.63
      (0.55-0.72) for Alzheimer's disease, 0.31 (0.19-0.51) for vascular dementia and
      0.45 (0.12-1.69) for other dementia. In a model adjusting for confounding
      variables, a light-to-moderate intake of beer was associated with a significantly
      higher risk of dementia than a non-drinker of beer. For wine, a significantly
      lower risk of dementia existed for a light-to-moderate drinker. CONCLUSIONS:
      Light-to-moderate drinking was associated with a significantly lower risk of
      dementia compared with a non-drinker.

PMID- 16084642
TI  - Phox2B mutations and the Delta-Notch pathway in neuroblastoma.
AB  - We recently identified six neuroblastoma patients with constitutional or tumor
      specific mutations in the homeobox gene Phox2B. Phox2B controls part of the
      differentiation program of the sympathetic nervous system (SNS). Mice with a
      homozygous inactivation of Phox2B fail in the proper differentiation of the
      chromaffin lineage of the SNS. Phox2B regulates HASH1 which can control
      expression of genes of the Delta-Notch pathway. We previously showed that a
      subset of neuroblastoma cell lines highly expresses Delta-like 1 (Dlk1), which is
      a marker for the chromaffin lineage of the SNS. Notch3 is expressed in another
      subset of neuroblastoma cell lines and marks tumors from an alternative
      differentiation lineage. Phox2B is also related to the TrkA differentiation
      pathway in neuroblastoma. Here we will review the role of Phox2B in
      differentiation programs of the SNS and in neuroblastoma pathogenesis.

PMID- 16084643
TI  - Biosorption of Acid Red 274 (AR 274) on Enteromorpha prolifera in a batch system.
AB  - The biosorption of Acid Red 274 (AR 274) dye on Enteromorpha prolifera, a green
      algae grown on Mersin costs of the Mediterranean, Turkey, was studied as a
      function of initial pH, temperature, initial dye and biosorbent concentration.
      The experiments were conducted in a batch manner. The Langmuir and Freundlich
      isotherms were used for modelling the biosorption equilibrium. At optimum
      temperature 30 degrees C and initial pH 2.0-3.0, the Langmuir isotherm fits best
      to the experimental equilibrium data with a maximum monolayer coverage of 244
      mg/g. The equilibrium AR 274 concentration of the exit stream of a single batch
      was also obtained by using the experimental equilibrium curve and operating line
      graphically. The pseudosecond-order kinetic model and Weber-Morris model were
      applied to the experimental data and it was found that both the surface
      adsorption as well as intraparticle diffusion contribute to the actual adsorption
      process. The biosorption process follows a pseudosecond-order kinetics and
      activation energy was determined as -4.85 kJ/mol. Thermodynamic studies showed
      that the biosorption of AR 274 on E. prolifera is exothermic and spontaneous in
      nature.

PMID- 16084644
TI  - Transcriptional profiling of a mouse model for Lafora disease reveals
      dysregulation of genes involved in the expression and modification of proteins.
AB  - Lafora's progressive myoclonus epilepsy (Lafora disease: LD) is caused by
      mutations in the EPM2A or NHLRC1 gene, but cellular mechanisms of the
      pathogenesis remain unclear. In an attempt to understand and elucidate the
      disease pathway, we have investigated the global gene expression profile in a
      mouse model for LD that developed a phenotype similar to that observed in human
      patients, including presence of Lafora bodies, neurodegeneration and profound
      neurological disturbances. We found 62 differentially expressed genes in the
      Epm2a knockout mice brains. These genes encode factors involved in protein
      catabolism, phosphatase, transcription factors, and molecules involved in protein
      translation, and homeostasis. The two largest functional groups of mRNAs that
      showed altered expression were predicted to be involved in post-translational
      modification of proteins and transcriptional regulation, suggesting that defects
      in protein activity and/or turnover may be the key trigger in the pathophysiology
      of LD. Furthermore we show that changes in gene expression are not limited to
      brain and are seen in other organs that develop Lafora bodies. Our study may
      provide valuable insights into the pathophysiology of LD and may aid in
      developing potential therapeutic targets.

PMID- 16084646
TI  - Reversible inhibition of contractions of mammalian cardiomyocytes and of smooth
      muscle by the protistan parasite Leishmania major.
AB  - Myotropic neuropeptides have been isolated from vertebrates and invertebrates.
      Recently, a myoinhibitory peptide from the protist Leishmaniamajor was isolated,
      and its function in the sand fly vector was described. Similar lysates of
      cultured L. major were tested for their ability to inhibit contractions in
      mammalian cell and tissue preparations. L. major proteins (LMP) (34 microg/ml)
      completely stopped spontaneous contractions of cultured rat cardiomyocytes; cells
      resumed contracting after a saline wash. An application of 880 microg/ml LMP
      significantly decreased force of contractions (36%) in strips of guinea pig ileum
      precontracted with nicotine (p<0.01) but not with acetylcholine (p>0.01). Ileal
      strips rinsed with Tyrode's solution and again stimulated with nicotine
      contracted normally. Contractile force of ileal strips electrically stimulated
      with 40 V was reduced in a dose-dependent manner (30, 76, and 100%) (p<0.01) by
      increasing concentrations of LMP (220, 440, and 880 microg/ml). This ileal
      preparation resumed contracting after rinsing with Tyrode's solution. Oxytocin
      induced contractions of guinea pig uterine strips were reduced significantly in a
      dose-dependent manner (21 and 55%) (p<0.01) by increasing concentrations (170 and
      310 microg/ml) of LMP and resumed contracting normally after rinsing with
      Tyrode's solution. Modes of action for L. major myoinhibitory factors may include
      either decreasing Ca(2+) influx or increasing Ca(2+) efflux in susceptible
      muscle. Protistan-induced inotropism is discussed in light of exacerbating
      pathology of disease.

PMID- 16084645
TI  - Integration of engrafted Schwann cells into injured peripheral nerve: axonal
      association and nodal formation on regenerated axons.
AB  - Transplantation of myelin-forming cells can remyelinate axons, but little is
      known of the sodium channel organization of axons myelinated by donor cells.
      Sciatic nerve axons of female wild type mice were transected by a crush injury
      and Schwann cells (SCs) from green fluorescence protein (GFP)-expressing male
      mice were transplanted adjacent to the crush site. The male donor cells were
      identified by GFP fluorescence and fluorescence in situ hybridization (FISH) for
      Y chromosome. In nerves of GFP-expressing mice, GFP was observed in the axoplasm
      and in the cytoplasmic compartments of the Schwann cells, but not in the myelin.
      Following transplantation of GFP-SCs into crushed nerve of wild type mice, immuno
      electron microscopic analysis indicated that GFP was observed in the cytoplasmic
      compartments of engrafted Schwann cells which formed myelin. Nodal and paranodal
      regions of the axons myelinated by the GFP-SCs were identified by Na(v)1.6 sodium
      channel and Caspr immunostaining, respectively. Nuclear identification of the Y
      chromosome by FISH confirmed the donor origin of the myelin-forming cells. These
      results indicate that engrafted GFP-SCs participate in myelination of regenerated
      peripheral nerve fibers and that Na(v)1.6 sodium channel, which is the dominant
      sodium channel at normal nodes, is reconstituted on the regenerated axons.

PMID- 16084647
TI  - The bed nucleus of the stria terminalis in the Syrian hamster: subnuclei and
      connections of the posterior division.
AB  - The bed nucleus of the stria terminalis is a key part of a ring of cells
      extending between the centromedial amygdala and bed nucleus of the stria
      terminalis referred to as the extended amygdala. The present study describes the
      architecture of the bed nucleus of the stria terminalis and the connections of
      subnuclei in posterior bed nucleus of the stria terminalis. The hamster bed
      nucleus of the stria terminalis is readily allotted to anterior and posterior
      divisions separated by the fibers of the body of the anterior commissure. The
      anterior division has four subnuclei: anteromedial, anterointermediate,
      anterolateral, and anteroventral. Within the posterior division, there are three
      distinct regions: posteromedial, posterointermediate, and posterolateral. In
      hamsters, the posterior bed nucleus of the stria terminalis contributes to male
      sexual behavior, particularly chemoinvestigation. Moreover, the posterior bed
      nucleus of the stria terminalis is part of a neural circuit essential for mating,
      including the medial amygdaloid nucleus and medial preoptic area. The connections
      of bed nucleus of the stria terminalis, posteromedial part, bed nucleus of the
      stria terminalis, posterointermediate part and bed nucleus of the stria
      terminalis, posterolateral part were visualized by co-injection of anterograde
      (Phaseolus vulgaris leucoagglutinin) and retrograde (cholera toxin B) tract
      tracers. The bed nucleus of the stria terminalis, posterointermediate part and
      bed nucleus of the stria terminalis, posteromedial part have dense bidirectional
      connections with medial amygdaloid nucleus and cortical amygdala via the stria
      terminalis and ventral amygdalofugal pathway. These subnuclei also maintain
      bidirectional connections with steroid-concentrating areas including lateral
      septum, medial preoptic area, hypothalamus, and periaqueductal gray. The bed
      nucleus of the stria terminalis, posterointermediate part and bed nucleus of the
      stria terminalis, posteromedial part receive projections from the subiculum and
      send projections to deep mesencephalic nuclei. By contrast, the bed nucleus of
      the stria terminalis, posterolateral part is connected with the central amygdala,
      lateral hypothalamus, subthalamic nucleus, nucleus accumbens, substantia
      innominata, substantia nigra and thalamus. Thus, the bed nucleus of the stria
      terminalis, posterointermediate part and bed nucleus of the stria terminalis,
      posteromedial part have similar connections with areas involved in social
      behaviors. The bed nucleus of the stria terminalis, posterolateral part maintains
      connections with areas involved in motivational circuits. This supports the
      concept of distinct circuits within the extended amygdala which differentially
      link the centromedial amygdala and bed nucleus of the stria terminalis.

PMID- 16084648
TI  - PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel
      neuroprotectant, elicits its function in primary neuronal cultures by up
      regulating Bcl-2 expression.
AB  - Neurotoxicity in primary neurons was induced using hypoxia/hypoglycemia (H/H),
      veratridine (10microM), staurosporine (1microM) or glutamate (100microM), which
      resulted in 72%, 67%, 75% and 66% neuronal injury, respectively. 3-Aminopyridine
      2-carboxaldehyde thiosemicarbazone (PAN-811; 10microM; Panacea Pharmaceuticals,
      Gaithersburg, MD) pretreatment for 24 h provided maximal neuroprotection of 89%,
      42%, 47% and 89% against these toxicities, respectively. Glutamate or H/H
      treatment of cells increased cytosolic cytochrome c levels, which was blocked by
      pretreatment of cells with PAN-811. Pretreatment of neurons with PAN-811 produced
      a time-dependent increase in the protein level of Bcl-2, which was evident even
      after glutamate or H/H treatments. An up-regulation in the expression of the p53
      and Bax genes was also observed following exposure to these neurotoxic insults;
      however, this increase was not suppressed by PAN-811 pretreatment. Functional
      inhibition of Bcl-2 by HA14-1 reduced the neuroprotective efficacy of PAN-811.
      PAN-811 treatment also abolished glutamate or H/H-mediated internucleosomal DNA
      fragmentation.

PMID- 16084649
TI  - Effects of single and continuous administration of amyloid beta-peptide (25-35)
      on adenylyl cyclase activity and the somatostatinergic system in the rat frontal
      and parietal cortex.
AB  - It is unknown whether the amyloid beta-peptide (Abeta), a principal component
      found in extracellular neuritic plaques in the brain of patients with Alzheimer's
      disease (AD), is capable of altering adenylyl cyclase (AC) activity and the
      somatostatin (SRIF) receptor-effector system in the cerebral cortex of the
      patients. Therefore, the objective of this study was to investigate the effect of
      the beta fragment, beta (25-35), on AC activity and the somatostatinergic system
      in the rat frontoparietal cortex. A single dose of beta (25-35) (10microg)
      injected intracerebroventricularly significantly decreased the density of SRIF
      receptors (27.4%) and increased their affinity (32.2%) in the frontoparietal
      cortex. The inhibitory effect of SRIF on basal and forskolin (FK)-stimulated AC
      activity was significantly lower in the beta (25-35)-treated rats when compared
      with controls. beta (25-35) did not modify Gialpha1, Gialpha2 nor Gialpha3 levels
      in membranes from the frontoparietal cortex. Continuous infusion of the peptide
      induced a decrease in the SRIF receptor density in this brain area to a similar
      extent as that observed 14 days after the single administration of the peptide.
      Likewise, this treatment decreased the SRIF receptor density in the frontal
      cortex (15.3%) and parietal cortex (27.2%). This effect was accompanied by a
      decrease in the SRIF-mediated inhibition of FK-stimulated AC activity (from 41.6%
      to 25.6%) in the frontal cortex as well by a decrease in basal AC activity (from
      36.9% to 31.6%) and FK-stimulated AC activity (from 35.6% to 27.1%) in the
      parietal cortex. Continuous infusion of Abeta (25-35) had no effect on Gialpha1,
      Gialpha2 or Gialpha3 levels in membranes from frontal and parietal cortex.
      However, this treatment caused a decrease in SRIF-like immunoreactivity content
      in the parietal (38.9%) and frontal (20.4%) cortex. These results suggest that
      Abeta might be involved in the alterations of somatostatinergic system reported
      in AD.

PMID- 16084650
TI  - Memory consolidation and reconsolidation of an inhibitory avoidance task in mice:
      effects of a new different learning task.
AB  - CF-1 male mice were trained in an inhibitory avoidance task using a high
      footshock (1.2mA, 50Hz, 1 s) in order to reduce the influence of extinction on
      retention performance. A single session of 5 min exposure to a hole-board (nose
      poke behavior), either immediately after training or the first retention test
      (memory reactivation) impaired retention performance over two consecutive days.
      The effects were time-dependent since they were not observed when the exposure to
      the hole-board was delayed 3 h. When mice were habituated to the hole-board (5
      min/day, 5 days), and then trained in an inhibitory avoidance task, the
      immediately post-training or memory reactivation exposure to the hole-board did
      not modify retention performance over two consecutive days. The effects of the
      post-reactivation acute exposure to the hole-board were long-lasting (21 days).
      Reinstatement was not observed in our experimental conditions. The non
      spontaneous recovery of retention performance over 21-days and the lack of
      reinstatement, suggest that the impairment of retention performance observed was
      not probably due to a deficit in memory retrieval. These findings suggest that
      the exposure to a potential new learning situation impairs not only memory
      consolidation but also memory reconsolidation of the original learning task.

PMID- 16084651
TI  - Involvement of the retinohypothalamic tract in the photic-like effects of the
      serotonin agonist quipazine in the rat.
AB  - Light is the major synchronizer of the mammalian circadian pacemaker located in
      the suprachiasmatic nucleus. Photic information is perceived by the retina and
      conveyed to the suprachiasmatic nucleus either directly by the retinohypothalamic
      tract or indirectly by the intergeniculate leaflet and the geniculohypothalamic
      tract. In addition, serotonin has been shown to affect the suprachiasmatic
      nucleus by both direct and indirect serotonin projections from the raphe nuclei.
      Indeed, systemic as well as local administrations of the serotonin agonist
      quipazine in the region of the suprachiasmatic nucleus mimic the effects of light
      on the circadian system of rats, i.e. they induce phase-advances of the locomotor
      activity rhythm as well as c-FOS expression in the suprachiasmatic nucleus during
      late subjective night. The aim of this study was to localize the site(s) of
      action mediating those effects. Phase shifts of the locomotor activity rhythm as
      well as c-FOS expression in the suprachiasmatic nucleus after s.c. injection of
      quipazine (10 mg/kg) were assessed in Lewis rats, which had received either radio
      frequency lesions of the intergeniculate leaflet or infusions of the serotonin
      neurotoxin 5,7-dihydroxytryptamine into the suprachiasmatic nucleus (25 microg)
      or bilateral enucleation. Lesions of intergeniculate leaflet and serotonin
      afferents to the suprachiasmatic nucleus did not reduce the photic-like effects
      of quipazine, whereas bilateral enucleation and the subsequent degeneration of
      the retinohypothalamic tract abolished both the phase-shifting and the FOS
      inducing effects of quipazine. The results indicate that photic-like effects of
      quipazine are mediated via the retinohypothalamic tract.

PMID- 16084652
TI  - Facilitation of enkephalins-induced delta-opioid behavioral responses by chronic
      amisulpride treatment.
AB  - The endogenous opioid system is known to have a great influence on the
      dopaminergic system. Conversely, blockade of the dopaminergic system in D2
      receptor knock-out mice triggers an increase in enkephalin supporting the
      important physiological relationship between both systems. Therefore, the aim of
      this study was to investigate whether or not chronic treatment with the specific
      D2 antagonist amisulpride (20mg/kg, i.p., twice daily for 5 days) could lead to a
      facilitation of behavioral effects of enkephalins, protected from their enzymatic
      degradation by the dual inhibitor N-[(R,S)-2-benzyl-3[(S)(2-amino-4
      methylthio)butyl dithio]-1-oxopropyl]-l-phenylalanine benzyl ester (RB101)
      (5mg/kg, i.v.) in mice. RB101 induced an increase in locomotor activity,
      antidepressant-like effects in the forced swim test, and antinociceptive effects
      in the hot-plate test. Chronic treatment with amisulpride potentiated the action
      of RB101 and this effect seemed to be restricted to behavioral responses induced
      by opioids acting on delta-opioid receptors (locomotor activity and forced swim
      test). This was confirmed by the use of the selective delta-opioid receptor
      agonist, (+)-4-[alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3
      methoxybenzyl]-N,N-diethylbenzamide (SNC80; 2.5mg/kg, i.p.), and antagonist,
      naltrindole (5mg/kg, i.p.). Considering the involvement of delta-opioid receptors
      in mood regulation, the interaction between amisulpride and RB101 could lead to a
      new therapeutic approach in the treatment of some mood disorders.

PMID- 16084653
TI  - Sexually dimorphic expression of oxytocin binding sites in forebrain and spinal
      cord of the rat.
AB  - The central actions of oxytocin on reproduction-related functions and behaviors
      are strongly steroid-dependent and gender specific. This study characterizes
      sexual differences in the oxytocin binding site expression in forebrain and
      spinal cord of the rat. Using film autoradiography, we quantified the density of
      oxytocin binding sites in the ventromedial hypothalamic nucleus, the medial and
      central nuclei of the amygdala, the medial bed nucleus of the stria terminalis
      and the spinal cord dorsal horns both in adult male and female rats, and during
      development. In addition, neonatal castrated males and intact neonatal females
      treated with a single injection of testosterone (1 mg) were examined. Data showed
      a sexual dimorphism in the expression of oxytocin binding sites in the spinal
      cord dorsal horns and in restricted areas of the forebrain that are sensitive to
      gonadal steroids such as the ventromedial hypothalamic nucleus, but not in
      gonadal steroid insensitive sites such as the central nucleus of the amygdala.
      Adult males had higher oxytocin binding site densities in the ventromedial
      hypothalamic nucleus and dorsal horns than females. In the forebrain, but not in
      the dorsal horn, this sexual difference required a perinatal exposure to
      testosterone. Neonatal castration only abolished the sexual difference in the
      ventromedial hypothalamic nucleus of adults, but not in the dorsal horn.
      Furthermore, females that received a single injection of testosterone 1 day after
      birth showed significant increases in the density of oxytocin binding sites in
      the ventromedial hypothalamic nucleus, medial nucleus of the amygdala and medial
      bed nucleus of the stria terminalis. In addition, the findings suggest that the
      sexual difference in the ventromedial hypothalamic nucleus also requires gonadal
      hormones in adulthood. Our data support the hypothesis that sexually dimorphic
      oxytocin binding sites may contribute to the regulatory central actions of
      oxytocin in gender specific functions and behaviors such as nociception and
      reproduction.

PMID- 16084654
TI  - Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat
      sensory neurons.
AB  - We have localized cannabinoid receptor 2 protein in rat and mouse somatic sensory
      nervous system, using an antibody that recognizes mouse cannabinoid receptor 2.
      Little or no cannabinoid receptor 2 immunoreactivity was found in sections of
      naive rat or mouse dorsal root ganglia or spinal cord. This was in accord with
      the lack of detectable cannabinoid receptor 2 mRNA in (dorsal root ganglion)
      neurons by in situ hybridization experiments described in the literature.
      However, we could detect cannabinoid receptor 2 immunoreactivity following
      unilateral nerve damage-either by sciatic nerve section, or by spinal nerve
      ligation. It was localized to the superficial laminae of the dorsal horn of the
      spinal cord, ipsilateral to the nerve damage, coincident with the area of
      termination of damaged afferents which was marked by loss of isolectin B4
      binding. This upregulation was not seen in cannabinoid receptor 2 null mice. The
      cannabinoid receptor 2 protein in spinal cord appeared to be expressed on sensory
      neuron afferent terminals as it colocalized with two markers of damaged
      afferents, namely growth associated protein-43 and the neuropeptide galanin.
      Moreover, it did not colocalize with markers of activated microglial cells (OX
      42) or astroglial cells (glial fibrillary acidic protein) in rat spinal cord. In
      the peripheral nerve, accumulation of cannabinoid receptor 2 immunoreactivity was
      seen in nerve sections proximal, but not distal, to the ligation site, suggesting
      transport down the nerve from the cell bodies. Although convincing cannabinoid
      receptor 2 immunoreactivity was seen in neither uninjured nor injured dorsal root
      ganglion neuron cell bodies in tissue sections, expression was detectable in
      isolated, cultured neurons that had received a prior axotomy in vivo. This clear
      demonstration of CB(2) receptors on sensory neurons suggests an additional
      cellular target for CB(2) agonist induced analgesia, at least in neuropathic
      models.

PMID- 16084655
TI  - Recruitment of synapses in the neurosecretory process during long-term
      facilitation at the lobster neuromuscular junction.
AB  - We investigated long-term facilitation at the lobster neuromuscular synapse
      employing a combination of FM1-43 staining of synaptic vesicles, electron
      microscopy analysis, and electrical recordings of synaptic activity. Synaptic
      terminals were loaded with the fluorescent dye FM1-43 producing clusters of
      activity-dependent fluorescent spots. Electron microscopy analysis of synaptic
      ultrastructure suggested that fluorescent spots represent compartments of
      synaptic terminals filled with vesicles. Excitatory postsynaptic currents were
      recorded from the stained synaptic terminals using focal macropatch electrodes.
      Terminals were stained during the nerve stimulation at a low stimulation
      frequency (2, 5 or 10 Hz) before and after long-term facilitation was elicited by
      high-frequency stimulation (20 or 30 Hz for 5 min). We found that staining after
      long-term facilitation results in the appearance of new fluorescent spots, as
      well as in the increase in fluorescence of the spots that appeared before long
      term facilitation. This increase in fluorescence accounted for the increase in
      quantal release. Activation of individual fluorescent spots was found to be non
      uniform. In spite of overall increase in fluorescence, some synaptic compartments
      decreased their staining after long-term facilitation. Thus, our study
      demonstrates that long-term facilitation produces non-uniform activation of FM1
      43 uptake in synaptic compartments that correlates with the increase in quantal
      neurosecretion.

PMID- 16084656
TI  - Biophysical properties of the silent and activated rat sympathetic neuron
      following denervation.
AB  - A biophysical description of the denervated rat sympathetic neuron is reported,
      obtained by the two-electrode voltage-clamp technique in mature intact superior
      cervical ganglia in vitro. At membrane potential values negative to -50 mV, the
      normal, quiescent neuron displays voltage-dependent K and Cl conductances;
      following direct or synaptic stimulation (15Hz for 10 s), the neuron moves to a
      new resting state characterized by increased amplitude and voltage dependence of
      Cl conductance. Denervation produces two main effects: 1) resting Cl conductance
      gradually increases while its voltage-dependence decreases; by 30 days a high
      conductance resting state prevails, almost independent of membrane potential in
      the -50/-110 mV range; 2) the increase in amplitude and voltage-dependence of Cl
      conductance, produced by direct stimulation in control neurons, is less marked in
      denervated neurons, and is observed over an increasingly small range of membrane
      potentials. Thirty days after denervation, the prevailing high-conductance
      resting state appears virtually insensitive to changes in membrane potential and
      stimulation. Voltage-dependent potassium currents involved in spike
      electrogenesis (the delayed compound potassium current and the fast transient
      potassium current) exhibit an early drastic decrease in peak amplitude in the
      denervated neuron; the effect is largely reversed after 6 days. Remarkable
      changes in fast transient potassium current kinetics occur following denervation:
      the steady-state inactivation curve shifts by up to +15 mV toward positive
      potential and voltage sensitivity of inactivation removal becomes more steep. A
      comprehensive mathematical model of the denervated neuron is presented that fits
      the neuron behavior under current-clamp conditions. It confirms that neuronal
      excitability is tuned by the conductances (mostly chloride conductance) that
      control the resting membrane potential level, and by fast transient potassium
      current. Impairment of the latter reduces both inward threshold charge for firing
      and spike repolarization rate, and fast transient potassium current failure
      cancels the voltage dependence of both processes.

PMID- 16084657
TI  - Ultra-low-dose naloxone suppresses opioid tolerance, dependence and associated
      changes in mu opioid receptor-G protein coupling and Gbetagamma signaling.
AB  - Opiates produce analgesia by activating mu opioid receptor-linked inhibitory G
      protein signaling cascades and related ion channel interactions that suppress
      cellular activities by hyperpolarization. After chronic opiate exposure, an
      excitatory effect emerges contributing to analgesic tolerance and opioid-induced
      hyperalgesia. Ultra-low-dose opioid antagonist co-treatment blocks the excitatory
      effects of opiates in vitro, as well as opioid analgesic tolerance and
      dependence, as was demonstrated here with ultra-low-dose naloxone combined with
      morphine. While the molecular mechanism for the excitatory effects of opiates is
      unclear, a switch in the G protein coupling profile of the mu opioid receptor and
      adenylyl cyclase activation by Gbetagamma have both been suggested. Using CNS
      regions from rats chronically treated with vehicle, morphine, morphine+ultra-low
      dose naloxone or ultra-low-dose naloxone alone, we examined whether altered mu
      opioid receptor coupling to G proteins or adenylyl cyclase activation by
      Gbetagamma occurs after chronic opioid treatment. In morphine-naive rats, mu
      opioid receptors coupled to Go in striatum and to both Gi and Go in
      periaqueductal gray and spinal cord. Although chronic morphine decreased Gi/o
      coupling by mu opioid receptors, a pronounced coupling to Gs emerged coincident
      with a Gbetagamma interaction with adenylyl cyclase types II and IV. Co-treatment
      with ultra-low-dose naloxone attenuated both the chronic morphine-induced Gs
      coupling and the Gbetagamma signaling to adenylyl cyclase, while increasing Gi/o
      coupling toward or beyond vehicle control levels. These findings provide a
      molecular mechanism underpinning opioid tolerance and dependence and their
      attenuation by ultra-low-dose opioid antagonists.

PMID- 16084658
TI  - Calcium channels modulate nociceptive transmission in the trigeminal nucleus of
      the cat.
AB  - Clinical observations and genetic studies have suggested a role for high
      threshold voltage-dependent calcium channels (VDCCs) in the pathogenesis of
      migraine. This study investigated the role of P/Q-, L- and N-type VDCCs in post
      synaptic action potential generation in trigeminovascular nociceptive afferents
      in the trigeminocervical complex (TCC) of the cat in vivo. Trigeminovascular
      nociceptive afferents were identified in the TCC by electrical stimulation of the
      superior sagittal sinus. Forty-six cell bodies were identified by their response
      to microiontophoresis of l-glutamate and their bipolar action potential shape.
      Blockade of VDCCs was accomplished by microiontophoresis of omega-agatoxin IVa/TK
      (P/Q-), omega-conotoxin GVIa (N-) and calciseptine (L-type). Non-selective
      antagonism was studied using cadmium ions. Non-selective blockade of high
      threshold VDCC with cadmium resulted in a reduction in l-glutamate-evoked
      neuronal activity (P=0.01). Blockade of P/Q: TK- (P<0.001), IVA- (P=0.007), L-
      (P<0.001) and N-type (P<0.001) VDCCs resulted in significant reductions in post
      synaptic action potential generation in response to l-glutamate. High threshold
      VDCCs, including P/Q-, L- and N-type VDCCs, can therefore modulate nociceptive
      transmission in the trigeminocervical complex in vivo. We discuss the evidence to
      suggest a role for VDCCs in the pathophysiology of primary headache disorders,
      and how abnormalities of function may contribute to their pathogenesis.

PMID- 16084659
TI  - Nucleus accumbens nitric oxide immunoreactive interneurons receive nitric oxide
      and ventral subicular afferents in rats.
AB  - The nitric oxide generating neurons of the nucleus accumbens exert a powerful
      influence over striatal function, in addition, these nitrergic inputs are in a
      position to regulate the dopaminergic and glutamatergic inputs on striatal
      projection neurons. It was the aim of this study to establish the source of the
      glutamatergic drive to nitric oxide synthase interneurons of the nucleus
      accumbens. The nucleus accumbens nitric oxide-generating neurons receive
      asymmetrical, excitatory, presumably glutamatergic inputs. Possible sources of
      these inputs could be the limbic and cortical regions known to project to this
      area. To identify sources of the excitatory inputs to the nitric oxide synthase
      containing interneurons of the nucleus accumbens in the rat we first examined the
      ultrastructural morphology of asymmetrical synaptic specializations contacting
      nitric oxide synthase-immunohistochemically labeled interneurons in the nucleus
      accumbens. Neurons were selected from different regions of the nucleus accumbens,
      drawn using camera lucida, processed for electron microscopic analysis, and the
      boutons contacting nitric oxide synthase-labeled dendrites were photographed and
      correlated to the drawings. Using vesicle size as the criterion the source was
      predicted to be either the prefrontal cortex or the ventral subiculum of the
      hippocampus. To examine this prediction, a further study used anterograde tracing
      from both the prefrontal cortex and the ventral subiculum, and nitric oxide
      synthase immunohistochemistry with correlated light and electron microscopy.
      Based on appositions by anterogradely labeled fibers, selected nitric oxide
      synthase-labeled neurons within the nucleus accumbens, were examined with
      electron microscopic analysis. With this technique we confirmed the prediction
      that subicular afferent boutons make synaptic contact with nitric oxide synthase
      interneurons, and demonstrated anatomically that nitric oxide synthase boutons
      make synaptic contact with the dendritic arbors of nitric oxide synthase
      interneurons. We suggest that the subicular input may excite the nitric oxide
      synthase neurons synaptically, while the nitric oxide synthase-nitric oxide
      synthase interactions underlie a nitric oxide signaling network which propagates
      hippocampal information, and expands the hippocampus's influence on 'gating'
      information flow across the nucleus accumbens.

PMID- 16084660
TI  - Evidence for an intrinsic mechanism of antinociceptive tolerance within the
      ventrolateral periaqueductal gray of rats.
AB  - Repeated microinjections of morphine into the ventrolateral periaqueductal gray
      produce antinociceptive tolerance. This tolerance may be a direct effect of
      morphine on cells within the ventrolateral periaqueductal gray or may require
      activation of downstream structures such as the rostral ventromedial medulla or
      spinal cord. Experiment 1 examined whether tolerance develops when opioid
      receptors in the ventrolateral periaqueductal gray are blocked prior to repeated
      systemic morphine administration. Microinjections of naltrexone hydrochloride
      (1microg/0.4microl) into the ventrolateral periaqueductal gray blocked
      antinociception and significantly attenuated the development of antinociceptive
      tolerance produced from systemic morphine administration. Experiment 2 examined
      whether tolerance develops when the effects of morphine are isolated to the
      ventrolateral periaqueductal gray. This was accomplished by microinjecting
      morphine (5microg/0.4microl) into the ventrolateral periaqueductal gray while
      simultaneously blocking the descending output through the rostral ventromedial
      medulla. Inhibition of neurons within the rostral ventromedial medulla by
      microinjecting the GABA(A) agonist muscimol (10ng/0.5microl) blocked the
      antinociception produced by microinjection of morphine into the ventrolateral
      periaqueductal gray but did not block the development of tolerance. These data
      demonstrate that the ventrolateral periaqueductal gray is both necessary and
      sufficient to produce tolerance to the antinociceptive effect of morphine. The
      ventrolateral periaqueductal gray is necessary in that tolerance does not develop
      if opiate action within the ventrolateral periaqueductal gray is blocked
      (experiment 1). The ventrolateral periaqueductal gray is sufficient in that
      tolerance occurs even when morphine's effects are restricted to the ventrolateral
      periaqueductal gray (experiment 2).

PMID- 16084661
TI  - Differential expression of vesicular glutamate transporters by vagal afferent
      terminals in rat nucleus of the solitary tract: projections from the heart
      preferentially express vesicular glutamate transporter 1.
AB  - The central projections and neurochemistry of vagal afferent neurones supplying
      the heart in the rat were investigated by injecting cholera toxin B-subunit into
      the pericardium. Transganglionically transported cholera toxin B-subunit was
      visualized in the medulla oblongata in axons and varicosities that were
      predominantly aggregated in the dorsomedial, dorsolateral, ventrolateral and
      commissural subnuclei of the caudal nucleus of the solitary tract. Unilateral
      vagal section in control rats prevented cholera toxin B-subunit labeling on the
      ipsilateral side of the nucleus of the solitary tract. Fluorescent and electron
      microscopic dual labeling showed colocalization of immunoreactivity for vesicular
      glutamate transporter 1, but only rarely vesicular glutamate transporters 2 or 3
      with cholera toxin B-subunit in terminals in nucleus of the solitary tract,
      suggesting that cardiac vagal axons release glutamate as a neurotransmitter. In
      contrast, populations of vagal afferent fibers labeled by injection of cholera
      toxin B-subunit, tetra-methylrhodamine dextran or biotin dextran amine into the
      aortic nerve, stomach or nodose ganglion colocalized vesicular glutamate
      transporter 2 more frequently than vesicular glutamate transporter 1. The
      presence of other neurochemical markers of primary afferent neurones was examined
      in nucleus of the solitary tract axons and nodose ganglion cells labeled by
      pericardial cholera toxin B-subunit injections. Immunoreactivity for a 200-kDa
      neurofilament protein in many large, cholera toxin B-subunit-labeled nodose
      ganglion cells indicated that the cardiac afferent fibers labeled are mostly
      myelinated, whereas binding of Griffonia simplicifolia isolectin B4 to fewer
      small cholera toxin B-subunit-labeled ganglion cells suggested that tracer was
      also taken up by some non-myelinated axons. A few labeled nucleus of the solitary
      tract axons and ganglion cells were positive for substance P and calcitonin gene
      related peptide, which are considered as peptide markers of nociceptive afferent
      neurones. These data suggest that the population of cardiac vagal afferents
      labeled by pericardial cholera toxin B-subunit injection is neurochemically
      varied, which may be related to a functional heterogeneity of baroreceptive,
      chemoreceptive and nociceptive afferent fibers. A high proportion of cardiac
      neurones appear to be glutamatergic, but differ from other vagal afferents in
      expressing vesicular glutamate transporter 1.

PMID- 16084662
TI  - 17Beta-estradiol induced Ca2+ influx via L-type calcium channels activates the
      Src/ERK/cyclic-AMP response element binding protein signal pathway and BCL-2
      expression in rat hippocampal neurons: a potential initiation mechanism for
      estrogen-induced neuroprotection.
AB  - Our group and others have demonstrated that 17beta-estradiol (E2) induces
      neurotrophic and neuroprotective responses in hippocampal and cortical neurons
      which are dependent upon the Src/extracellular signal-regulated kinase (ERK)
      signaling pathways. The purpose of this study was to determine the upstream
      mechanism(s) that initiates the signaling cascade leading to E2-inducible
      neuroprotection. We tested the hypothesis that E2 activates rapid Ca(2+) influx
      in hippocampal neurons, which would lead to activation of the Src/ERK signaling
      cascade and up-regulation of Bcl-2 protein expression. Using fura-2 ratiometric
      Ca(2+) imaging, we demonstrated that E2 induced a rapid rise of intracellular
      Ca(2+) concentration ([Ca(2+)](i)) within minutes of exposure which was blocked
      by an L-type Ca(2+) channel antagonist. Inhibition of L-type Ca(2+) channels
      resulted in a loss of E2 activation of the Src/ERK cascade, activation of cyclic
      AMP response element binding protein (CREB) and subsequent increase in Bcl-2.
      Real-time intracellular Ca(2+) imaging combined with pERK immunofluorescence,
      demonstrated that E2 induced [Ca(2+)](i) was coincident with ERK activation in
      the same neuron. Small interfering RNA knockdown of CREB resulted in a loss of E2
      activation of CREB and subsequent E2-induced increase of Bcl-2 expression. We
      further demonstrated the presence of specific membrane E2 binding sites in
      hippocampal neurons. Together, these data indicate that E2-induced Ca(2+) influx
      via the L-type Ca(2+) channel is required for E2 activation of the
      Src/ERK/CREB/Bcl-2 signaling. Implications of these data for understanding
      estrogen action in brain and use of estrogen therapy for prevention of
      neurodegenerative disease are discussed.

PMID- 16084663
TI  - Gender and environmental effects on regional brain-derived neurotrophic factor
      expression after experimental traumatic brain injury.
AB  - Alterations in brain-derived neurotrophic factor expression have been reported in
      multiple brain regions acutely after traumatic brain injury, however neither
      injury nor post-injury environmental enrichment has been shown to affect
      hippocampal brain-derived neurotrophic factor gene expression in male rats
      chronically post-injury. Studies have demonstrated hormone-related
      neuroprotection for female rats after traumatic brain injury, and estrogen and
      exercise both influence brain-derived neurotrophic factor levels. Despite recent
      studies suggesting that exposure post-traumatic brain injury to environmental
      enrichment improves cognitive recovery in male rats, we have shown that
      environmental enrichment mediated improvements with spatial learning are gender
      specific and only positively affect males. Therefore the purpose of this study
      was to evaluate the effect of gender and environmental enrichment on chronic post
      injury cortical and hippocampal brain-derived neurotrophic factor protein
      expression. Sprague-Dawley male and cycling female rats were placed into
      environmental enrichment or standard housing after controlled cortical impact or
      sham surgery. Four weeks post-surgery, hippocampal and frontal cortex brain
      derived neurotrophic factor expression were examined using Western blot. Results
      revealed significant increases in brain-derived neurotrophic factor expression in
      the frontal cortex ipsilateral to injury for males (P=0.03). Environmental
      enrichment did not augment this effect. Neither environmental enrichment nor
      injury significantly affected cortical brain-derived neurotrophic factor
      expression for females. In the hippocampus ipsilateral to injury brain-derived
      neurotrophic factor expression for both males and females was half (49% and 51%
      respectively) of that observed in shams housed in the standard environment. For
      injured males, there was a trend in this region for environmental enrichment to
      restore brain-derived neurotrophic factor levels to sham values. However, there
      were robust increases in hippocampal brain-derived neurotrophic factor expression
      ipsilateral to the injury for injured females in environmental enrichment
      compared with both sham and injured females placed in standard housing
      (P<or=0.005). In the hippocampus contralateral to injury, there were also
      significant injury-related increases in brain-derived neurotrophic factor
      expression for females (P<or=0.05) that were not further augmented by
      environmental enrichment. These results show significant, region-specific gender
      differences in brain-derived neurotrophic factor expression with both injury and
      environmental enrichment that may be important for recovery. However, these data
      do not support a critical role for brain-derived neurotrophic factor in
      environmental enrichment mediated improvements with spatial learning.

PMID- 16084665
TI  - Long-term sleep apnea as a pathogenic factor for cell-mediated autoimmune
      disease.
AB  - BACKGROUND: Previous medical literature has shown that cell injury from hypoxia,
      such as that induced by sleep apnea, leads to hyperuricemia. Furthermore, a
      recent study has shown that when hyperuricemia reaches sufficient concentration
      to precipitate as monosodium urate, a T-cell immune response is triggered. The
      frequent repetition of this cell injury and immune response over a prolonged
      time, as would occur with long-term sleep apnea, may lead to the development,
      continuation, or aggravation of autoimmune disease. HYPOTHESIS: Long-term sleep
      apnea is hypothesized to be a pathogenic factor in the development of cell
      mediated autoimmune disease. Several corollaries are presented along with this
      general hypothesis. First, some of the diseases associated with sleep apnea may
      have an autoimmune etiology. Second, some autoimmune diseases not usually
      recognized to be associated with sleep apnea may indeed have that association.
      Third, resolving sleep apnea in some patients with autoimmune disease to remove
      that autoimmune stimulus may aid in deceleration, halt, or even reversal of the
      progress of the autoimmune disease. Fourth, because monosodium urate also causes
      gouty arthritis in some individuals, diagnosis of gout may allow for resolution
      of sleep apnea early enough to prevent autoimmune development. Fifth,
      allopurinol, which suppresses uric acid generation, may be an effective therapy
      for the remission or prevention of a number of autoimmune diseases. CONCLUSION:
      This hypothesis strengthens the evidence pointing to the danger of unresolved
      sleep apnea by a mechanism previously unrecognized, namely the risk of developing
      an autoimmune disease. As a result of this realization, new therapies may be
      adopted for the treatment and prevention of autoimmune disease, specifically,
      resolving sleep apnea and the use of allopurinol.

PMID- 16084664
TI  - Differential expression of arc mRNA and other plasticity-related genes induced by
      nicotine in adolescent rat forebrain.
AB  - Relatively little attention has been focused on mechanisms related to neural
      plasticity and drug abuse in adolescence, compared with abundant research using
      adult animal models. As smoking is typically initiated in adolescence, an
      important question to address is whether the adolescent brain responds
      differently to nicotine compared with the adult. To investigate this question, we
      examined the expression of a number of early response genes (arc, c-fos and NGFI
      B) that have been implicated in synaptic plasticity and addiction, following
      acute nicotine in adolescent and adult rats. Baseline expression of arc and c-fos
      was higher in adolescent brains compared with adults. Following acute nicotine
      treatment (0.1, 0.4mg/kg), we found a marked induction of arc mRNA in the
      prefrontal cortex of nicotine-treated adolescents compared with a less pronounced
      increase of arc in the adult. c-fos and NGFI-B were also upregulated by nicotine,
      but not in an age-related manner. In contrast, nicotine induced less arc, c-fos,
      and NGFI-B expression in the somatosensory cortex of adolescents compared with
      adults. A fourth gene, quinoid dihydropteridine reductase was expressed at lower
      levels in white matter of the adolescent forebrain compared with the adult, but
      was not affected by nicotine. These results suggest that in adolescence, the
      activity of specific early response genes is higher in brain regions critical for
      emotional regulation and decision-making. Further, nicotine affects key
      plasticity molecules in these areas in a manner different from the adult. Thus,
      adolescence may represent a neurobiologically vulnerable period with regard to
      nicotine exposure.

PMID- 16084666
TI  - High-dose zinc to terminate angina pectoris: a review and hypothesis for action
      by ICAM inhibition.
AB  - We reviewed the literature related to the effects of high-dose zinc in
      arteriosclerosis-induced angina pectoris. Lipid peroxidation and LDL oxidation
      are believed to be critical for arteriosclerosis, and consequently angina
      pectoris. Administration of biologically available zinc was a beneficial
      treatment in a significant percentage of patients with severely symptomatic,
      inoperable atherosclerotic disease. In these patients, there was no difference in
      zinc concentration between patients with and without atherosclerosis in whole
      blood, erythocytes or hair, but there was a major difference between normal aorta
      and diseased aortas (40.6 ppm zinc in normal aorta vs. 23.2 ppm zinc in
      atherosclerotic aorta, 40.6 ppm zinc in normal aorta vs. 19.4 ppm zinc in
      atherosclerotic aneurysm aorta, and no difference between normal and aneurysm
      aorta), although copper was low in aneurysm aorta. Medication with high-dose zinc
      sulfate to raise zinc serum concentrations from 95 to 177 microg/dl resulted in
      objective improvement in 12 of 16 of these patients, including a patient that
      also had Raynaud's disease. Long term environmental exposure to zinc resulted in
      a 40% reduction in the incidence of angina of effort compared to people not
      exposed to environmental zinc (P<0.01) and a 40% reduction in the incidence of
      probable ischemia in exercise (P<0.001). Lead had no effect while cadmium
      exposure resulted in more than tripling the incidence of angina of effort
      (P<0.001). The antioxidative action of zinc prevents oxidation of LDL cholesterol
      and consequently stops the main mechanism of atherogenesis. Zinc blocks calcium
      and its several actions on atherogenesis. Increased amounts of cytotoxic
      cytokines such as TNF-alpha, IL-beta and IL-8, often produced in the elderly, are
      blocked by high-dose zinc. We hypothesize that higher serum concentrations of LDL
      cholesterol resulting from administration of 300 mg of zinc per day is caused by
      a release of low density cholesterol from cardiovascular tissues, beneficially
      flushing it into the serum where it is readily observed, thus decreasing
      arteriosclerosis, increasing circulation, terminating angina pectoris and
      restoring more youthful cardiac function. Although prevention of cholesterol
      induced arteriosclerosis by zinc is predicted from findings related to oxidative
      stress and lipid peroxidation, removal of LDL might be attributable to action of
      ionic zinc on ICAM inhibition. In stark contrast to current practice, high-dose
      zinc should be considered as basic in the strategy of prophylaxis and therapy of
      the atherosclerosis process to terminate angina pectoris and restore youthful
      cardiac function.

PMID- 16084667
TI  - Differentiation therapy of cancer. Potential advantages over conventional
      therapeutic approaches targeting death of cancer/tumor cells.

PMID- 16084668
TI  - Mechanisms involved in the neural construction of a body-centered reference axis
      for extrapersonal directed movements. A hypothesis.
AB  - To localize objects in space, it is necessary to refer them to a set of
      coordinates that serve as a frame of reference. Advances in molecular aspects of
      evolutionary developmental biology reveal how axial coordinates are established
      in embryos. But we do not yet know how axes of reference are constructed by adult
      animals. The characteristics of epaxial musculature, spinal connectivity, and
      organization at the cortical level are reviewed. Although endowed with muscle
      spindles, epaxial muscles lack the monosynaptic but possess the tonic component
      of the stretch reflex. Motoneurons of epaxial muscles are devoid of recurrent
      inhibition and do not show crossed disynaptic inhibition. At motorsensory cortex
      (MSC), regions corresponding to the body axis receive somatosensory signals that
      always extend across the midline. Visual and vestibular input also converge in
      the zone corresponding to the body axis. This region is also endowed with a large
      number of callosal fibers that, by connecting the two halves of the body axis,
      may allow them to function and behave as a unity. In contrast, somatic signals
      from distal extremities are discrete, confined only to the contralateral MSC, and
      show short latency of responses. They do not receive either telereceptive or
      vestibular input. We propose that limb movements directed to extrapersonal space
      take place within a reference frame in which one of the axes is the result of
      integration at the MSC of telereceptive, proprio and somatosensory signals from
      the body. Vestibular input signals the effect of the force of gravity, providing
      directionality to the axis.

PMID- 16084669
TI  - T waves are independently generated in both right and left ventricles: the
      clinically recorded T is a summation of two separate repolarizations, and is thus
      always biventricular.
AB  - The T-wave of the electrocardiogram (ECG) is generated both from the left and the
      right ventricles of the heart. Each ventricle may produce a normal, an
      "ischemic", or a "secondary" T-wave, depending on segmental perfusion,
      intraventricular pressure, or QRS complex duration. The direction of the T-wave
      is determined by the particular inward rectifier potassium channels recruited by
      various layers and segments in the two ventricles. The observed T-wave in the
      clinical ECG is the summation of the left and right ventricular T waves, and is
      thus biventricular. Clinical observations in right bundle branch block (RBBB) and
      in right ventricular hypertensive states such as pulmonary embolism suggest that
      many ECG's interpreted as inferior or anterior left ventricular ischemia are in
      fact examples of abnormal potassium channel recruitment in the right ventricle.
      Consideration of the right ventricular component of the T-wave in every
      electrocardiographic interpretation improves diagnostic understanding and
      accuracy, as the possible right ventricular origin of observed anterior or
      superior T waves will not be overlooked.

PMID- 16084670
TI  - Thrombotic thrombocytopenic purpura: proposal of a new pathogenic mechanism
      involving Helicobacter pylori infection.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a severe, occlusive, thrombotic
      microangiopathy characterized by a systemic platelet aggregation, organ ischemia,
      profound thrombocytopenia and erythrocyte fragmentation. Recent observations have
      documented that a deficiency of a von Willebrand factor (VWF)-cleaving protease,
      termed ADAMTS13, that normally cleaves hyper-reactive unusually large VWF
      multimers into smaller and less adhesive VWF forms, may be responsible for many
      cases of TTP. Multiple mutations of the ADAMTS13 gene can result in ADAMTS13
      deficiency and cause congenital TTP, while autoantibodies neutralizing ADAMTS13
      protease activity have been associated with acquired TTP. However, in spite of
      the recent progresses in the pathophysiology of TTP, many aspects of this disease
      remain still controversial. In this study, basing on the laboratory results of a
      group of eight patients with an acquired form of TTP, an alternative pathogenic
      mechanism for TTP involving Helicobacter pylori infection is proposed. In fact,
      Helicobacter pylori, which has been recently implied in the pathogenesis of
      idiopathic thrombocytopenic purpura (ITP), could function as a triggering factor
      in TTP by inducing platelet aggregation through an interaction with VWF.

PMID- 16084671
TI  - Increased ratio of saturated to unsaturated C18 fatty acids in colonic
      adenocarcinoma: implications for cryotherapy and lipid raft function.
AB  - Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of
      human malignancies including colonic adenocarcinoma. Since FASE synthesizes only
      saturated fatty acids, we hypothesized that cancer cells have a greater
      proportion of long-chain saturated fatty acids. We studied and found an
      unequivocal increase in saturated C18 fatty acid (stearic acid) in colonic
      adenocarcinoma compared to adjacent normal colonic mucosa. The increase is even
      more striking when measured as a ratio of stearic acid to the unsaturated C18
      fatty acids (oleic acid and linoleic acid). This change in fatty acid composition
      of the cancer cells should significantly alter their physical and biological
      properties. The increase in relative proportion of saturated fatty acids should
      make the cancer cells more susceptible to cryodamage and measurement of fatty
      acid composition of cancer cells may help individualize the temperature for
      cryotherapy. Also, the lipid alterations may affect the structure and functions
      of lipid rafts, which may enable the cancer cells to affect signaling mechanisms
      such as those involved in cell growth and apoptosis. Dietary or therapeutic
      interventions targeting lipid rafts may thus be an option for cancer treatment.

PMID- 16084672
TI  - Trigeminal neuralgia is caused by maxillary and mandibular nerve entrapment:
      greater incidence of right-sided facial symptoms is due to the foramen rotundum
      and foramen ovale being narrower on the right side of the cranium.
AB  - Trigeminal neuralgia (TN) is the most important disease of the trigeminal nerve.
      Vascular compression of the dorsal root of the trigeminal nerve by aberrant loop
      of blood vessels is currently accepted as the most common cause of TN. The right
      side of the face is affected by TN twice as often as the left side, but there are
      no anatomical reasons for the blood vessels loop to be more frequent on the right
      side of the cranial fossa. Additionally, vascular compression in asymptomatic
      patients and in TN patients without aberrant blood vessels has been reported,
      thereby arguing against the idea that vascular compression alone is responsible
      for TN. Anatomical and radiological studies have shown that the rotundum and
      ovale foramens on the right side of the human cranium are significantly narrower
      than on the left side. The rotundum and ovale foramens are crossed by the
      maxillary and mandibular nerves, respectively, and are the nerves most affected
      in TN. Based on demographic and epidemiological data of TN patients, and on
      anatomical findings in the foramens, we hypothesized that entrapment of the
      maxillary and mandibular nerves when they cross the ovale and rotundum foramens
      is a primary cause of TN and accounts for the higher incidence of TN on the right
      sided.

PMID- 16084673
TI  - Do different portions of the boar ejaculate vary in their ability to sustain
      cryopreservation?
AB  - Previous studies have shown sperm quality post-cryopreservation differs depending
      on the fraction of the seminal plasma boar spermatozoa are fortuitously contained
      in. As such, spermatozoa contained in the first 10 mL of the sperm-rich fraction
      (portion I) have better sustained handling procedures (extension, handling and
      freezing/thawing) than those contained in the ulterior part of a fractionated
      ejaculate (second portion of the sperm-rich fraction and the post-spermatic
      fraction, portion II). However, those studies were performed using pooled
      samples. In the present study, individual ejaculates were used. Split ejaculates
      (portions I and II) from five boars were frozen and thawed using a conventional
      freezing protocol, followed by computer-assisted motility and morphology analysis
      (CASA and ASMA, respectively), as well as an Annexin-V assay for spermatozoa from
      each boar and ejaculate portion. Significant differences between portions were
      observed in all ASMA-derived variables, except in one boar. Also significant
      differences were observed between boars and ejaculate portions in sperm quality
      post-thaw. We identified, however, boars showing best results of motility and
      sperm membrane integrity post-thaw in portion I, while in other boar the best
      results was observed in portion II. It is concluded that the identification of
      the ejaculate portion more suitable to sustain cryopreservation in each
      individual boar may be a readily applicable and easy technique to diminish
      variation in sperm freezability among boars.

PMID- 16084674
TI  - Biochemical characterization and membrane fluidity of membranous vesicles
      isolated from boar seminal plasma.
AB  - Mammalian seminal plasma contains membranous vesicles (MV), which differ in
      composition and origin. Among these particles, human prostasomes and equine
      prostasome-like MV have been the most studied. The aim of the present work is to
      characterize the biochemical composition and membrane fluidity of MV isolated
      from boar seminal plasma. The MV from boar seminal plasma were isolated by
      ultracentrifugation and further purification by gel filtration on Sephadex G-200.
      The MV were examined by electron microscopy (EM), amount of cholesterol, total
      phospholipid, protein content, and phospholipid composition were analyzed.
      Membrane fluidity of MV and spermatozoa were estimated from the electron spin
      resonance (ESR) spectra of the 5-doxilstearic acid incorporated into the vesicle
      membranes by the order parameter (S). The S parameter gives a measure of degree
      of structural order in the membrane and is defined as the ratio of the spectral
      anisotropy in the membranes to the maximum anisotropy obtained in a rigidly
      oriented system. The S parameter takes into consideration that S = 1 for a rapid
      spin-label motion of about only one axis and S = 0 for a rapid isotropic motion.
      Intermediate S values between S = 0 and S = 1 represents the consequence of
      decreased membrane fluidity. The EM revealed the presence of bilaminar and
      multilaminar electron-dense vesicles. Cholesterol to phospholipid molar ratio
      from the isolated MV was 1.8. Phospholipid composition showed a predominance of
      sphingomyelin. The S parameter for porcine MV and for boar spermatozoa was 0.73
      +/- 0.02 and 0.644 +/- 0.008, respectively, with the S for MV being greater (p <
      0.001) than the S for spermatozoa. The high order for S found for boar MV was in
      agreement with the greater cholesterol/phospholipids ratio and the lesser ratio
      for phosphatidylcholine/sphingomyelin. Results obtained in the present work
      indicate that MV isolated from boar semen share many biochemical and
      morphological characteristics with equine prostasome-like MV and human
      prostasomes. The characteristics of the porcine MV of the seminal plasma,
      however, differed from those of boar sperm plasma membranes.

PMID- 16084675
TI  - Relation between reproductive, physiological, and immunological condition of
      Litopenaeus setiferus pre-adult males fed different dietary protein levels
      (Crustacea; Penaeidae).
AB  - The present study was designed to evaluate the effect of amount of dietary
      protein levels on blood indicators of protein metabolism and immune condition
      (blood protein, hemocyanin, osmotic pressure, and hemocytes concentrations), and
      reproductive capacity of pre-adult Litopenaeus setiferus males (F0). Assessments
      were made of the relationship between amount of dietary protein, immune
      condition, and reproductive condition of the shrimp during the maturation
      process. Three different diets, with different amounts of protein (DP; 35, 45,
      and 55%), were evaluated over 55 days and compared with shrimp that were from a
      baseline group before treatments were administrated. Osmotic pressure,
      hemocyanin, blood protein, and hemocytes were greater in shrimp from control
      ponds than those obtained of shrimp fed 35 and 45% DP and similar to that
      obtained in shrimp fed 55% DP, demonstrating that food in the control pond had a
      nutritional value to that obtained by feeding amounts of dietary protein beyond
      45%. Osmotic pressure, hemocyanin (Hc), blood protein (BP), and hemocytes were
      influenced by amount of DP with the physiology and immune system of shrimp being
      influenced by diet. At the same time, a maximum reproductive condition (measured
      as a proportion of normal cells of the total sperm cells) of shrimp males was
      observed in shrimp fed 45% DPL with lesser normal cells being present in shrimp
      fed 35 and 55% DPL. These results indicate that an immune reaction can occur in
      response to dietary protein with excess DP affecting several physiological
      functions included the sperm synthesis and sperm quality. Influence on hemocytes
      concentration in shrimp fed protein in excess could activate an attack on sperm
      cells in the vas deferens provoking lose of sperm quality in such conditions.
      Results indicate an optimal DP of 45 for maintaining the broodstock bank of L.
      setiferus.

PMID- 16084676
TI  - Maintaining contact with bucks does not induce refractoriness to the male effect
      in seasonally anestrous female goats.
AB  - A study was performed to determine if complete separation between sexes is a pre
      requisite to stimulate sexual activity of anovulatory female goats by male
      exposure in mid-anestrus when reproductive activity is greatly inhibited. The
      response to the male was studied in anovulatory goats which had either been in
      contact with bucks before the stimulation (n = 22; CONT), or totally isolated
      from bucks (n = 22; ISOL). At the time of male exposure, the bucks from the CONT
      groups were removed and females of both groups (CONT and ISOL) were divided into
      two subgroups (n = 11) exposed to novel bucks (n = 1 per subgroup), either in
      sexual rest (sexually inactive; SI) or in which sexual activity had been induced
      by a photoperiodic treatment (sexually active; SA). The sexual behavior of the SA
      bucks during the first 5 days of stimulation was greater than that of SI bucks (P
      < 0.01). Regardless of whether females had been (82%) or not (91%) exposed to
      bucks before teasing, most goats stimulated by SA males displayed estrous
      behavior and ovulation in the first 15 days following stimulation, whereas no
      female from the two subgroups exposed to SI bucks showed estrous behavior and
      only one of them ovulated (P < 0.02). These results indicate that previous
      isolation of seasonally anovulatory goats from bucks is not required to stimulate
      their reproductive activity by the male effect, if sexually active bucks are
      used.

PMID- 16084677
TI  - Intermittent versus indwelling urinary catheterization in older female patients.
AB  - OBJECTIVES: To compare the use of intermittent and indwelling catheterization in
      older female patients with urinary retention. METHODS: A randomized, 2-week
      prospective study in a geriatric rehabilitation ward. Female patients of age 65
      years and older with post-voiding residual urine volume (PVRU) persistently > or
      = 300 ml were randomly assigned to one of the two groups: intermittent
      catheterization (IMC group, n=36) and indwelling catheterization (IDC group,
      n=45). The primary outcome was the proportion of subjects being catheter-free and
      had a PVRU < 150 ml on day 14. The secondary outcomes were the time to become
      catheter-free and the rate of bacteriuria on day 14. RESULTS: Sixteen out of 27
      (59.3%) in the IMC group versus 27 out of 39 (69.2%) in the IDC group achieved
      the primary outcome on day 14 (P=.403) without significant difference in the
      PVRU. The IMC and IDC groups took a mean of 8.6+/-3.3 and 9.2+/-4.0 days to
      become catheter-free, respectively (P=.609). Fourteen out of 22 (63.6%) in the
      IMC group versus 21 out of 34 (61.8%) in the IDC group had bacteriuria on day 14
      (P=.888). CONCLUSION: Given the similar success rate of regaining bladder voiding
      function, the similar rate of bacteriuria and considering that the IMC group only
      underwent a median of 3 times of intermittent catheterization, we believe that
      the approach of intermittent urinary catheterization when required would be
      justified in managing elderly female urinary retention in rehabilitation ward as
      the presence of indwelling catheters would hinder rehabilitation and adversely
      affect patient quality of life.

PMID- 16084678
TI  - Protective effect of calcineurin inhibitors on acoustic injury of the cochlea.
AB  - This study examined the effect of immunosuppressants, cyclosporin A, FK506 and
      rapamycin on functional recovery of the cochlea after acoustic overexposure, in
      guinea pigs and mice. Thirty guinea pigs were exposed to a 2 kHz pure tone at 120
      dB SPL for 10 min. The compound action potential threshold shift induced by
      acoustic overexposure was examined. Twenty-five mice were exposed to a 4 kHz pure
      tone at 128 dB SPL for 4h. Auditory brainstem response was used to examine the
      hearing threshold shift. In both the guinea pig and mouse experiments,
      cyclosporin A and FK506, intraperitonally given just before acoustic
      overexposure, significantly decreased the hearing threshold shift one or two
      weeks after acoustic overexposure. However, neither rapamycin nor the FK506 and
      rapamycin combined treatment groups showed improvement of the threshold shift.
      The present findings suggest that these two calcineurin inhibitors have a
      protective effect against acoustic injury of the cochlea, whereas the non
      calcineurin inhibitor, rapamycin, not only has no effect against acoustic injury,
      but rather blocked the effect of FK506. This indicated a possible role of
      calcineurin against acoustic injury.

PMID- 16084679
TI  - "Zahraa", a Unani multicomponent herbal tea widely consumed in Syria: components
      of drug mixtures and alleged medicinal properties.
AB  - In Unani system of medicine, drugs consist of complex formulae with more than
      three components, for which, literature analysing these mixtures as they are sold
      in the market is scarce. In this paper, the main botanical components of the
      herbal tea known as "Zahraa" in Damascus, which contains between 6 and 14 species
      components is elucidated: Alcea damascena (Mout.) Mout. (Malvaceae), Aloysia
      triphylla (L'Herit.) Britt. (Malvaceae), Astragalus cf. amalecitanus Boiss.,
      Cercis siliquastrum L. subsp. hebecarpa (Bornm.) Yalt. and subsp. siliquastrum.
      (Leguminosae), Colutea cilicica Boiss. et Bal. in Boiss. (Leguminosae), Crataegus
      aronia (L.) Bosc. ex DC. (Rosaceae), Cytisopsis pseudocytisus (Boiss.) Fertig.
      (Leguminosae), Eleagnus angustifolia L. (Eleagnaceae), Equisetum telmateia Ehrh.
      (Equisetaceae), Helichrysum stoechas (L.) Moench. subsp. barrelieri (Ten.) Nyman.
      (Compositae), Matricaria recutita L. (Compositae), Mentha longifolia L. subsp.
      noeana (Boiss. ex. Briq.) Briq. (Labiatae), Mentha spicata L. subsp. condensata
      (Briq.) Greuter and Burdet (Labiatae), Micromeria myrtifolia Boiss. and Hohen. in
      Boiss. (Labiatae), Paronychia argentea Lam. (Caryophyllaceae), Phlomis syriaca
      Boiss. (Labiatae), Rosa damascena Mill. (Rosaceae), Salvia fruticosa Mill.
      (Labiatae), Sambucus nigra L. (Caprifoliaceae), Spartium junceum L.
      (Leguminosae), Zea mays L. (Gramineae).

PMID- 16084680
TI  - Analysis of Indian blue ballpoint pen inks tagged with rare-earth
      thenoyltrifluoroacetonates by inductively coupled plasma-mass spectrometry and
      instrumental neutron activation analysis.
AB  - Characterization and assessment of inks on sensitive documents for
      absolute/relative age determination is the challenging forensic problem in spite
      of practical difficulties. Tagging of ballpoint pen ink with suitable taggant(s)
      is a unique method to come out with definitive inferences on the detection of
      forgery in documents written with ballpoint pens. Selection of a proper taggant
      primarily depends on sensitivity of analytical determination and their absence in
      normal varieties of ink used for document writing. Rare-earth elements, from all
      technical considerations can be potential taggant(s) for inks. To ensure more
      compatibility with ink, 13 rare-earth thenoyltrifluoroacetonate chelates were
      prepared and characterized. The ballpoint pen inks were tagged with rare-earth
      thenoyltrifluoroacetonate chelates individually at about 1-100 ppm level
      depending on sensitivity of element under suitable optimized experimental
      conditions and instrumental sensitivity. Aliquots of such tagged ink having
      varying amounts of taggants were analyzed by ICP-MS and INAA. Satisfactory
      recoveries and a good linear relationship of intensity (signal) against
      concentrations/amounts were observed. Under the optimized experimental
      conditions, the detection limits were worked out. This study of tagging metal
      ions in combination with ICP-MS and NAA as an analytical tool can allow to draw
      various combination options based on different rare-earth chelates as suitable
      materials for tagging of ballpoint pen inks for absolute/relative age
      determination to aid in document related crime examination. The advantages and
      limitations of proposed analytical techniques are discussed.

PMID- 16084681
TI  - The role of sentinel lymph node biopsy in ductal carcinoma in situ.
AB  - AIM: To review the role of sentinel lymph node (SLN) biopsy in the surgical
      management of patients with ductal carcinoma in situ (DCIS). METHODS: A search
      was conducted of Medline and the National Library of Medicine to identify key
      articles concerning DCIS, SLN biopsy (SLNB) and axillary dissection. Further
      relevant articles were obtained from the references cited in the literature.
      RESULTS: Up to 20% of patients with a core biopsy diagnosis of DCIS will be later
      up-staged based on an invasive component identified on the excision specimen.
      Quality assurance in breast screening programmes requires minimally invasive pre
      operative diagnosis and also axillary sampling in the case of documented invasive
      disease. As an effective and validated procedure, SLNB represents a paradigm
      shift in the surgical management of the axilla for patients with invasive breast
      cancer. It remains undefined which, if any, subgroups of patients with DCIS
      should undergo SLNB. CONCLUSION: Axillary lymphadenectomy is an overtreatment for
      patients with DCIS. Performing a SLNB during the initial procedure may avoid a
      second operation in some DCIS patients who are diagnosed with occult invasive
      disease at their definitive operation. When predictors of hidden invasive disease
      are clarified by further study, SLNB may be used in the management of selected
      high-risk DCIS patients.

PMID- 16084682
TI  - The use of in situ hybridization and immunohistochemistry to study the
      pathogenesis of various Newcastle disease virus strains and recombinants in
      embryonated chicken eggs.
AB  - Avian paramyxovirus type 1, commonly referred to as Newcastle disease virus
      (NDV), is a serious pathogen of significant economic importance to the industry.
      To investigate the role of the fusion (F), hemagglutinin-neuraminidase (HN), and
      (P) phosphoprotein gene sequences in virulence, six strains of Newcastle disease
      virus (NDV) representing all pathotypes and seven recombinant strains created by
      reverse genetics were inoculated into 9-day-old chicken embryos. Tissues and
      chorioallantoic membranes (CAM) were harvested at 24-hour intervals post
      inoculation. Riboprobe in situ hybridization and immunohistochemistry highlighted
      distinct tissue tropisms among the viruses. Presence of F and/or HN from virulent
      viruses inserted into lentogenic backbones caused dissemination of virus in a
      manner similar to wild type virulent viruses. Disruption of P gene decreased
      dissemination of velogeinic infectious clones. It is concluded that each of these
      genes contributes to pathogenicity.

PMID- 16084683
TI  - Absence of complement receptor 3 results in reduced binding and ingestion of
      Mycobacterium tuberculosis but has no significant effect on the induction of
      reactive oxygen and nitrogen intermediates or on the survival of the bacteria in
      resident and interferon-gamma activated macrophages.
AB  - The interaction of host macrophage (Mphi) and Mycobacterium tuberculosis (Mtb) is
      mediated by cell surface receptors and is important in establishing intracellular
      infection. Mphis can kill invading organisms via reactive oxygen intermediates
      (ROI) and reactive nitrogen intermediates (RNI). Using a Complement Receptor 3
      (CR3) knockout mouse model we have examined whether the presence of CR3 affects
      the binding and uptake of viable Mtb by Mphis, the survival of the ingested
      bacteria and the induction of ROI and RNI during this interaction. We show that,
      although CR3 plays a role in the uptake of viable Mtb, the receptor plays no role
      in the subsequent survival of the bacteria. The finding holds true for resident
      Mphis and for interferon-gamma (IFN-gamma) activated Mphis, both in the absence
      and presence of serum opsonins. Activation of Mphi populations with IFN-gamma
      significantly inhibits the growth of Mtb in host Mphis and enhances the
      production of ROI and RNI. However, the presence of CR3 was not critical in any
      of these mechanisms. Furthermore, we demonstrate that the control of
      intracellular growth of Mtb in IFN-gamma activated Mphis is not mediated by a
      direct effect of RNI.

PMID- 16084684
TI  - Virulence of Burkholderia pseudomallei does not correlate with biofilm formation.
AB  - Burkholderia pseudomallei is the causative agent of melioidosis but currently the
      pathogenesis of the disease is still poorly understood. One of the virulent
      factors of gram-negative bacteria is the ability to produce biofilm to evade host
      defense. As B. pseudomallei has also been reported to develop the biofilm [1], in
      the present study, we therefore, quantified the biofilm formation in 50 strains
      of B. pseudomallei and compared with 50 strains of its avirulent counterpart
      Burkholderia thailandensis using a modified microtiter-plate test. The results
      showed that the quantity of biofilm produced by B. pseudomallei was statistically
      higher (P< 0.01) than that of B. thailandensis (means and SEs of the corrected
      OD630 were 2.17+/-0.29 and 0.59+/-0.05, respectively). Transmission electron
      micrographs of the B. pseudomallei strain with high biofilm formation exhibited
      microcolonies of bacterial cells surrounded by dense extracellular slime matrix
      comparing with only trace quantity in the low biofilm-producing strain or the
      biofilm mutants generated by Tn5-OT182 mutagenesis. However, no correlation could
      be observed between the biofilm formation and virulence, judging from the LD50
      values in BALB/c mice. The data obtained with these naturally occurring
      Burkholderia species and the biofilm mutants are incompatible with the
      possibility that the biofilm plays a role in the pathogenesis of B. pseudomallei
      infection.

PMID- 16084685
TI  - Human cord blood-derived neural stem cell line--possible implementation in
      studying neurotoxicity.
AB  - Neural stem cell line developed from human umbilical cord blood (HUCB-NSC)
      [Buzanska et al., 2003. Journal of Neurochemistry 85, 33] is an ethically
      uncontroversial source of stem cells, able to differentiate into neuronal,
      astrocytic and oligodendroglial lineages. Developmental fate decisions of HUCB
      NSC can be experimentally manipulated in vitro by the presence of trophic
      factors, mitogenes and neuromorphogenes, but can also be influenced by
      neurotoxins. In this report two-dimensional (2-D) and three-dimensional (3-D)
      HUCB-NSC cultures are introduced as useful models for testing developmental
      neurotoxicity. For 2-D culture models we established a standardized method for
      the assessment of the growth rate and cell differentiation in 96-well plates. The
      proliferative capacity of the HUCB-NSC was monitored by the MTT test while their
      ability to differentiate into neural-like cells by immunocytochemistry of beta
      tubulin III and MAP-2 for neurons, GFAP and S-100beta for astrocytes and GalC for
      oligodendrocytes. The 3-D culture of HUCB-NSC is represented by neurospheres.
      Proliferation and migration of the intermediate precursors from attached
      neurospheres are shown to be controlled and altered by various growth factors and
      further modulated by the extracellular matrix component-fibronectin. Thus,
      neurospheres derived from the HUCB-NSC line can represent a suitable model of the
      activation of dormant stem cells residing in their niche, and can be used for
      neurotoxic studies.

PMID- 16084686
TI  - Hope and coping in family members of patients with obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) affects approximately 2-4% of the adult
      population. Despite the practical and emotional demands of having a family member
      with OCD, few systematic attempts have been made to assess the coping strategies
      used by relatives of individuals with such diagnoses. In this study we examined
      the relationships between hope, coping strategies, and depressive symptoms in a
      heterogeneous sample of 67 spouses/primary caregivers of individuals with a
      history of OCD. In support of our hypotheses, hope was negatively related to
      depressive symptoms, symptom severity, and denial disengagement coping
      strategies, and positively related to active reframing and social support coping
      strategies. Active, Reframing, Social Support, and Religiosity were negatively
      related to depressive symptoms. Denial/Disengagement was positively associated
      with depressive symptoms. Coping mediated the relationship between hope and
      depressive symptoms. Given the importance of family members in treatment,
      clinical implications of these findings are discussed.

PMID- 16084687
TI  - Analysis of calcium-inducible genes in keratinocytes using suppression
      subtractive hybridization and cDNA microarray.
AB  - Terminal differentiation of skin keratinocytes is a vertically directed multistep
      process that is tightly controlled by the sequential expression of a variety of
      genes. To gain further insight into the molecular events involved in this
      process, we used suppression subtraction hybridization (SSH) and cDNA microarray
      analysis. Messenger RNAs were isolated from primary skin keratinocytes cultured
      in vitro after treatment with calcium and then SSH was performed. A total of 840
      cDNA clones were obtained from subtracted libraries, and these cDNA clones were
      used to make the microarray slides. Time-course cDNA microarray analysis (1, 3,
      7, and 14 days after calcium treatment) revealed the global gene expression
      profile during keratinocyte differentiation. Of the 840 genes tested, 290 showed
      a greater than twofold change in expression level at least once over four time
      points. The genes were clustered into six groups according to their expression
      pattern using self-organizing map analysis and showed the global feature of
      function-related regulation. The genes related to keratinocyte differentiation
      were markedly up-regulated by calcium treatment. In addition, a unique pattern of
      increase was seen in the expression of genes related to ribosomal proteins. On
      the other hand, transcripts involved in metabolism, DNA repair, transcription,
      and translation were generally down-regulated. These results demonstrate the
      complexity of the gene expression profile that contributes to the spatiotemporal
      regulation of keratinocyte differentiation.

PMID- 16084688
TI  - Insect psychoneuroimmunology: immune response reduces learning in protein starved
      bumblebees (Bombus terrestris).
AB  - It is well established in vertebrates that there are many intricate interactions
      between the immune system and the nervous system. Here, we present behavioural
      evidence indicating a link between the immune system and the nervous system in
      insects. We show that otherwise non-infected bumblebees whose immune systems were
      challenged by a non-pathogenic immunogenic elicitor (lipopolysaccharide) have
      reduced abilities to learn or recall a memory in a classical conditioning
      paradigm. There is evidence that protein is intricately involved as this immune
      induced reduction in memory only becomes apparent after the bees are deprived of
      pollen (their only protein sources).

PMID- 16084689
TI  - Increased nocturnal interleukin-6 excretion in patients with primary insomnia: a
      pilot study.
AB  - The aim of the present study was to investigate whether there is a difference in
      evening/nocturnal interleukin-6 (IL-6) serum excretion in patients with primary
      insomnia compared to controls. We hypothesized that in insomniac patients, the
      excretion of evening/nocturnal IL-6 is enhanced, like observed in aged adults and
      after sleep deprivation in healthy subjects. We studied IL-6 serum concentrations
      in 11 patients (two males and nine females) with primary insomnia and 11 age and
      gender-matched healthy controls. Sleep was monitored polysomnographically for
      three consecutive nights. The measurement of IL-6 (from 19:00 h to 09:00 h) in 2
      h intervals were performed prior to and during the last laboratory night.
      Polysomnographically determined sleep parameters and subjective ratings of sleep
      demonstrated clear-cut impairments of sleep in the insomniac group. Nocturnal IL
      6 secretion was significantly increased (p<.05) in insomniac patients for the
      whole measurement period (mean area under the curve+/-SD: 27.94+/-14.15 pg/ml x
      2h) compared to controls (16.70+/-7.64 pg/ml x 2h). Total IL-6 secretion
      correlated inversely with subjectively perceived sleep quality and amount of slow
      wave sleep in the insomniac patients. Amount of Wake Time correlated positively
      with IL-6 excretion in insomniacs. The results of the present study demonstrate
      significantly increased nocturnal IL-6 secretion in insomniacs. It might be
      speculated that chronic primary insomnia with polysomnographically documented
      sleep impairments activates the production of IL-6 analogous to sleep deprivation
      studies in healthy subjects. This might also implicate a higher risk for
      inflammatory and cardiovascular diseases in patients with chronic insomnia.

PMID- 16084690
TI  - High-throughput qualitative multiplex 5' nuclease assay using post-only PCR
      analysis.
AB  - Homogenous fluorescence PCR assays offer distinct advantages for qualitative
      testing and are gaining immense popularity in fields like diagnostic
      microbiology. To meet the demand of high-volume laboratories, we developed a
      protocol for qualitative multiplex 5' nuclease assays using post-only PCR
      analysis. This novel approach overcomes throughput problems encountered with the
      established methods for TaqMan detection on the ABI PRISM 7700 Sequence Detection
      system and permits off-site TaqMan PCR, which can be analyzed several days after
      the reactions are completed. We have validated this novel protocol using an assay
      for the identification of Bordetella pertussis against real-time and plate-read
      analysis methods and have shown that our proposed protocol produces no difference
      in qualitative calls.

PMID- 16084691
TI  - A SHPing tale: perspectives on the regulation of SHP-1 and SHP-2 tyrosine
      phosphatases by the C-terminal tail.
AB  - Protein tyrosine phosphorylation is a ubiquitous signalling mechanism and is
      regulated by a balance between the action of kinases and phosphatases. The SH2
      domain-containing phosphatases SHP-1 and SHP-2 are the best studied of the
      classical non-receptor tyrosine phosphatases, but it is intriguing that despite
      their close sequence and structural homology these two phosphatases play quite
      different cellular roles. In particular, whereas SHP-1 plays a largely negative
      signalling role suppressing cellular activation, SHP-2 plays a largely positive
      signalling role. Major sequence differences between the two molecules are
      apparent in the approximately 100 amino acid residues at the extreme C-terminus
      of the proteins, beyond the phosphatase catalytic domain. Here we review how the
      differences in the tails of these proteins may regulate their activities and
      explain some of their functional differences.

PMID- 16084692
TI  - Calcium-dependent regulation of NF-(kappa)B activation in cystic fibrosis airway
      epithelial cells.
AB  - Dysregulation of nuclear factor kappa B (NF-(kappa)B) and increased Ca(2+)
      signals have been reported in airway epithelial cells of patients with cystic
      fibrosis (CF). The hypothesis that Ca(2+) signaling may regulate NF-(kappa)B
      activation was tested in a CF bronchial epithelial cell line (IB3-1, CFTR
      genotype DeltaF508/W1282X) and compared to the CFTR-corrected epithelial cell
      line S9 using fluorescence microscopy to visualized in situ NF-(kappa)B
      activation at the single cell level. Upon stimulation with IL-1beta,we observed a
      slow but prolonged [Ca(2+)](i) increase (up to 10 min) in IB3-1 cells compared to
      S9 cells. The IL-1beta-induced [Ca(2+)](i) response was accompanied by an
      activation of NF-(kappa)B in IB3-1 but not in S9 cells. Pretreatment of IB3-1
      cells with the ER Ca(2+) pump inhibitor thapsigargin inhibited the IL-1beta
      induced [Ca(2+)](i) response. Treatment with either the calcium chelator BAPTA or
      an inhibitor of I(kappa)Balpha phosphorylation (digitoxin) led to a drastic
      [Ca(2+)](i) decrease accompanied by an inhibition of NF-(kappa)B activation of IL
      1beta-stimulated IB3-1 cells in comparison to untreated cells. In IB3-1 cells
      cultured at low temperature (26 degrees C) for 16 h, the IL-1beta-induced
      [Ca(2+)](i) response was inhibited and no significant NF-(kappa)B activation was
      observed. To our knowledge, this is the first report of visualization of the
      Ca(2+)-mediated activation of NF-(kappa)B in individual living airway epithelial
      cells. Our results support the concept that [Ca(2+)](i) is a key regulator of NF
      (kappa)B activation in CF airway epithelial cells.

PMID- 16084693
TI  - Long-term cosequences of intrahippocampal kainate injection in the Proechimys
      guyannensis rodent.
AB  - The Proechimys guyannensis (PG), a spiny rodent specie living in the Amazonian
      region has been recently studied as an animal model of anti-convulsant
      mechanisms. The PG was found to be resistant to the administration of the
      muscarinic cholinergic agonist pilocarpine or the amygdala kindling development.
      This study examined the susceptibility of this animal species to the
      intrahippocampal kainic acid (KA) injection. Electrographic, behavioral and
      neuropathological changes induced by intrahippocampal KA injections were
      analyzed. PG showed to be extremely sensitive to the acute effects of the KA
      injection. Although the EEG findings in PG rodents were similar to those
      typically obtained in Wistar rats the pattern of electrographic activity in PG
      animals was longer than in Wistar rats. Neuropathological examinations of PG
      brains that survived KA-induced SE revealed severe cell loss in CA1/CA3 areas of
      the hippocampus, an extensive cell dispersion in the hilus of DG at the injected
      site with mossy fiber sprouting in the dentate gyrus supragranular layer. None of
      PG animals presented spontaneous seizures during the 120 days of observation.
      These findings confirm our previous observation on the resistance of this animal
      specie to experimental models of limbic epilepsy.

PMID- 16084694
TI  - Individual changes in lamotrigine plasma concentrations during pregnancy.
AB  - Eleven pregnant women on lamotrigine (LTG) monotherapy were retrospectively
      reviewed. A significant decrease in the ratio of plasma LTG concentration-to-dose
      by 65.1% was observed during the second trimester (TM2) (p=0.0058) and by 65.8%
      during TM3 (p=0.0045) compared to pre-pregnancy values. Five patients experienced
      seizure deterioration during pregnancy. The pharmacokinetic changes display
      marked inter-patient variation, which stresses the importance of evaluating each
      woman individually by closely monitoring LTG concentrations until term.

PMID- 16084695
TI  - Genital automatisms in childhood partial seizures.
AB  - PURPOSE: To describe frequency and electroclinical characteristics as well as
      localizing and lateralizing value of childhood periictal genital automatisms
      (GAs). METHODS: Five-hundred-forty-one videotaped seizures of 109 consecutive
      patients <12 years with refractory partial epilepsy and postoperatively seizure
      free outcome were analyzed. Genital automatisms (scratching, fondling or grabbing
      of the genitals) were monitored by two independent investigators. RESULTS: Eight
      (four temporal, four extratemporal) patients (7%) showed GA at least once during
      20 (3.7%) seizures. Age of patients with GA was between 4.5 and 11.9 (mean 9.5+/
      2.4) years and was significantly higher than the age of children without GA
      (p=0.006). Boys showed GAs more frequently than girls (p=0.026). Genital
      automatisms appeared both ictally and postictally with a mean duration of 51s.
      They were unilateral (completed by one hand) in 18/20 seizures and were done by
      the hand ipsilateral to the seizure onset zone in 16/18 cases (p=0.001). Although
      consciousness was preserved during GA in 3/8 patients, neither periictal urinary
      urge nor penile erection was associated with it. CONCLUSIONS: Periictal GAs
      appear in school-age patients with a similar frequency to that in adults but
      almost lack in preschool children. Although the presence of childhood GA has
      neither localizing nor lateralizing value per se, the hand used for GA is more
      frequently ipsilateral to the seizure onset zone. The mechanisms for childhood
      GAs are not clear but probably different from those of adults.

PMID- 16084696
TI  - Schizophrenia and processing of facial emotions: sex matters.
AB  - The aim of this study was to examine sex differences in emotion processing in
      patients with schizophrenia and control subjects. To this end, 53 patients with
      schizophrenia (28 men and 25 women), and 42 controls (21 men and 21 women) were
      assessed with the use of a facial affect recognition morphing task. Accuracy and
      sensitivity scores were measured. Women performed better than men in labelling
      negative emotions. On the same task, patients performed worse than control
      subjects, irrespective of sex, although the largest degree of impairment was seen
      in male patients. In conclusion, emotion perception was disproportionally
      affected in men with schizophrenia relative to women. This may explain, in part,
      why women with schizophrenia are less impaired in social life than men suffering
      from this illness.

PMID- 16084697
TI  - Decreased caudal anterior cingulate gyrus volume and positive symptoms in
      schizophrenia.
AB  - The anterior cingulate gyrus is a heterogeneous region that has specialized
      subdivisions with respect to its cytoarchitecture, function and connectivity. The
      aim of this study was to examine the morphological changes of the caudal
      subdivision of the anterior cingulate gyrus in the context of the cortico
      striatal-thalamo-cortical circuitry of schizophrenia and their relationship to
      clinical symptoms. Accordingly, we measured the volumes of the caudal and rostral
      anterior cingulate gyrus, the orbitofrontal cortex, the caudate and the thalamus
      by magnetic resonance imaging in age- and sex-matched groups, which consisted of
      22 patients with schizophrenia and 22 normal volunteers. The clinical symptoms of
      schizophrenia patients were obtained using the Positive and Negative Syndrome
      Scale. Volumetric reduction of the right caudal anterior cingulate gyrus was
      observed in patients with schizophrenia as compared with the normal controls.
      Furthermore, a smaller volume of the caudal anterior cingulate gyrus was
      significantly correlated with more severe positive symptoms of schizophrenia.
      Thus, these findings suggest that a volumetric abnormality of the caudal anterior
      cingulate gyrus in schizophrenia may be related to positive symptoms and possibly
      involved in the pathophysiology of schizophrenia.

PMID- 16084698
TI  - The mechanism of lipopolysaccharide infiltration through HUVEC membrane surface
      in direct endotoxin injury.
AB  - In this study, the HUVEC's cellular biomechanical properties of HUVEC (elastic
      modulus K1, K2 and viscoefficient mu) were determined with micropipette
      aspiration system and analyzed after being directly damaged with
      lipopolysaccharide (LPS). The phospholipid compositions of HUVEC membrane were
      analyzed with high-performance capillary electrophoresis and PLA2 activity was
      determined to research the modification and metabolism of HUVEC membrane
      phospholipid. Infiltration of LPS on HUVEC membrane was studied by observation
      with confocal microscopy and fluorescent microscopy. Results showed that LPS
      direct injuring HUVEC can cause the changes of HUVEC biomechanical properties and
      membrane lipid contents; HUVEC directly damage by LPS could also activate HUVEC
      phospholipase A2 (PLA2), influencing membrane lipid metabolism; LPS could
      directly infiltrate and intercalate HUVEC membrane, causing and membrane contents
      variation. Based on these experimental results, the mechanism of
      lipopolysaccharide infiltration VEC membrane surface in direct LPS injury was
      studied and analyzed in view of the cellular biomechanical mechanism.

PMID- 16084699
TI  - Spray freeze drying to produce a stable Delta(9)-tetrahydrocannabinol containing
      inulin-based solid dispersion powder suitable for inhalation.
AB  - The purpose of this study is to investigate whether spray freeze drying produces
      an inhalable solid dispersion powder in which Delta(9)-tetrahydrocannabinol (THC)
      is stabilised. Solutions of THC and inulin in a mixture of tertiary butanol (TBA)
      and water were spray freeze dried. Drug loads varied from 4 to 30 wt.%. Various
      powder characteristics of the materials were determined. Stability of THC was
      determined and compared with freeze dried material. The powders, dispersed with
      an inhaler based on air classifier technology, were subjected to laser
      diffraction analysis and cascade impactor analysis. Highly porous particles
      having large specific surface areas (about 90 m(2)/g) were produced. At high drug
      loads, THC was more effectively stabilised by spray freeze drying than by freeze
      drying. Higher cooling rates during spray freeze drying result in improved
      incorporation. Fine particle fractions of up to 50% were generated indicating
      suitability for inhalation. It was concluded that spray freeze drying from a
      water-TBA mixture is a suitable process to include lipophilic drugs (THC) in
      inulin glass matrices. High cooling rates during the freezing process result in
      effective stabilisation of THC. The powders can be dispersed into aerosols with a
      particle size appropriate for inhalation.

PMID- 16084700
TI  - Homology, disruption and phenotypic analysis of CaGS Candida albicans gene
      induced during macrophage infection.
AB  - During macrophage infection Candida albicans expresses differentially several
      genes whose functions are associated with its survival strategy. Among others, we
      have isolated CaGS gene, which is homologous to SNF3, a glucose sensor of
      Saccharomyces cerevisiae. To elucidate its potential role during infection, CaGS
      has been disrupted and the resulting phenotype analyzed on different solid media.
      The null mutant lost the ability to form hyphae on a medium with low glucose
      concentration and serum. Furthermore, this mutant does not disrupt macrophage in
      in vitro infections. We believe that this putative glucose sensor is involved in
      hyphal development during macrophage infection.

PMID- 16084701
TI  - [Drugs news].

PMID- 16084702
TI  - [Central catheters and pericardial effusion: results of a multicentric
      retrospective study].
AB  - OBJECTIVE: To evaluate the use of neonatal central venous catheters (CVC) in 38
      french neonatal units and occurrence of pericardial effusion (PCE) over the past
      5 years. MATERIALS AND METHODS: We surveyed 38 units with a questionnaire and
      studied the cases of PCE in five units. RESULTS: Response rate was 89% (34/38).
      Accepted CVC tip positions were: junction of right atrium (RA) and vena cava (VC)
      76%, VC 58%, RA 11%. Fifty percent of the centers had been exposed to PCE. 16
      cases of PCE were studied. Median gestational age was 31 weeks (range: 26.1 to 40
      weeks). Median time from insertion: 3.2 days (range: 0.4-13.5). In all cases CVC
      tip was intracardiac at insertion with inadequate withdrawing in 13 cases. Sudden
      cardiac collapse was reported in eight cases, and unexplained cardiorespiratory
      instability in six cases. Echography showed PCE in 14 cases. One diagnosis was
      post-mortem. CVC was withdrawn in 12 patients and 13 underwent
      pericardiocentesis. Four patients died and two had neurological sequelae.
      CONCLUSION: PCE was associated with intracardiac CVC tip. The CVC tip should be
      controlled with radiography or echography outside the cardiac silhouette. PCE
      diagnosis must be considered in face of unexplained cardiovascular decompensation
      of neonate with CVC.

PMID- 16084703
TI  - [Clinical consequences of dioxins exposure during tooth development].
AB  - Commonly designed by the term "dioxins", polychlorinated aromatic hydrocarbons
      are environmental pollutants leading to several toxic effects during development
      and growth in embryo and child. The general consequences of dioxin exposure are
      particularly well-documented whereas only few data are mentioned by the experts
      concerning tooth development. However, studies performed in rodents have shown
      many disruptions during odontogenesis and enamel mineralisation. Moreover, recent
      epidemiological studies have demonstrated in human the incidence of dioxin
      exposure on enamel hypomineralisation and hypodontia. The aim of this review is
      to report recent data about consequences of dioxin exposure on tooth development,
      tooth being considered as a biological marker of potential dioxin poisoning.

PMID- 16084704
TI  - A model of motor control of the nematode C. elegans with neuronal circuits.
AB  - OBJECTIVE: Living organisms have mechanisms to adapt to various conditions of
      external environments. If we can realize these mechanisms on the computer, it may
      be possible to apply methods of biological and biomimetic adaptation to the
      engineering of artificial machines. This paper focuses on the nematode
      Caenorhabditis elegans (C. elegans), which has a relatively simple structure and
      is one of the most studied multicellular organisms. We aim to develop its
      computer model, artificial C. elegans, to analyze control mechanisms with respect
      to motion. Although C. elegans processes many kinds of external stimuli, we
      focused on gentle touch stimulation. METHODS: The proposed model consists of a
      neuronal circuit model for motor control that responds to gentle touch stimuli
      and a kinematic model of the body for movement. All parameters included in the
      neuronal circuit model are adjusted by using the real-coded genetic algorithm.
      Also, the neuronal oscillator model is employed in the body model to generate the
      sinusoidal movement. The motion velocity of the body model is controlled by the
      neuronal circuit model so as to correspond to the touch stimuli that are received
      in sensory neurons. CONCLUSION: The computer simulations confirmed that the
      proposed model is capable of realizing motor control similar to that of the
      actual organism qualitatively. By using the artificial organism it may be
      possible to clarify or predict some characteristics that cannot be measured in
      actual experiments. With the recent development of computer technology, such a
      computational analysis becomes a real possibility. The artificial C. elegans will
      contribute for studies in experimental biology in future, although it is still
      developing at present.

PMID- 16084705
TI  - Fuzzy attributes of a DNA complex: development of a fuzzy inference engine for
      codon-"junk" codon delineation.
AB  - OBJECTIVE: The present study is concerned with the need that exists in
      bioinformatics to identify and delineate overlapping codon and noncodon
      structures in a deoxyribonucleic acid (DNA) complex so as to ascertain the
      boundary of separation between them. Codons refer to those parts in a DNA complex
      encoded towards forming a desired set of proteins. Also coexist in the DNA
      structure noncodons (or "junk" codons), whose functions are not so well defined.
      Such codon and noncodon parts (at least over some sections of a DNA chain) may
      conform to diffused (overlapping) states exhibiting sharpless boundaries with
      indistinctive statistics of occurrence of their constituents. Such overlapping
      mix of codon and noncodon entities constitutes a (fuzzy) universe with
      information constituent having a fuzzy structure, which can only be identified in
      descriptive norms with characteristic membership of belonging to certain
      attributes. Hence, this work is directed to develop a fuzzy inference engine
      (FIE), which delineates the fuzzy codon-noncodon parts. METHODS AND MATERIAL:
      Relevant algorithms developed for the fuzzy inference in question are based on
      information-theoretic (IT) considerations applied to symbolic as well as binary
      sequence data representing the DNA. Pseudocodes, as needed are furnished.
      RESULTS: Simulated studies using human and other bacterial codon statistics are
      presented to illustrate the efficacy of the approach pursued. The outcome of the
      study is illustrated via tabulated results and graphs depicting the delineation
      sought. CONCLUSION: The results signify the success of IT-approach pursued in
      delineating imprecise codon/noncodon boundaries. The FIE applies both for human
      and bacterial codon statistics.

PMID- 16084706
TI  - Efficient RNAi-based gene family knockdown via set cover optimization.
AB  - OBJECTIVE: We address the problem of selecting an efficient set of initiator
      molecules (siRNAs) for RNA interference (RNAi)-based gene family knockdown
      experiments. Our goal is to select a minimal set of siRNAs that (a) cover a
      targeted gene family or a specified subset of it, (b) do not cover any untargeted
      genes, and (c) are individually highly effective at inducing knockdown. METHODS
      AND MATERIAL: We give two formalizations of the gene family knockdown problem.
      First, we show that the problem, minimizing the number of siRNAs required to
      knock down a family of genes, is NP-Hard via a reduction to the set cover
      problem. Second, we generalize the basic problem to incorporate additional
      biological constraints and optimality criteria. To solve the resulting set-cover
      variants, we modify the classical branch-and-bound algorithm to include some of
      these biological criteria. We find that in many typical cases these constraints
      reduce the search space enough that we are able to compute exact minimal siRNA
      covers within reasonable time. For larger cases, we propose a probabilistic
      greedy algorithm for finding minimal siRNA covers efficiently. We apply our
      methods to two different gene families, the FREP genes from Biomphalaria glabrata
      and the olfactory genes from Caenorhabditis elegans. RESULTS AND CONCLUSION: Our
      computational results on real biological data show that the probabilistic greedy
      algorithm produces siRNA covers as good as the branch-and-bound algorithm in most
      cases. Both algorithms return minimal siRNA covers with high predicted
      probability that the selected siRNAs will be effective at inducing knockdown. We
      also examine the role of "off-target" interactions: the constraint of avoiding
      covering untargeted genes can, in some cases, substantially increase the
      complexity of the resulting solution. Overall, we find that in many common cases
      our approach significantly reduces the number of siRNAs required in gene family
      knockdown experiments, as compared to knocking down genes independently.

PMID- 16084707
TI  - In vitro parameters of donor-antigen-specific tolerance.
AB  - Donor-antigen-specific tolerance to the allograft is increasingly considered a
      reachable goal in the field of transplantation. As our understanding of the
      processes that govern donor-specific tolerance increases, so must our
      understanding of ways to detect this state of affairs. Unfortunately, this is not
      a straightforward procedure, as the mechanisms which govern tolerance are
      multiple and varied. Previously, the mixed lymphocyte reaction was used as
      standard to detect unresponsiveness. This approach is not valid for detecting
      tolerance because it only measures both direct pathway, naive and memory
      responses, whereas the indirect pathway and 'pure' memory responses are more
      informative parameters for detecting tolerance. Techniques, such as the trans
      vivo delayed-type hypersensitivity assay, ELISPOT and antigen-specific HLA
      tetramer analysis address this problem, and the numbers of cell subsets, such as
      dendritic cells and NKT cells, can also aid us in detecting donor-antigen
      specific tolerance.

PMID- 16084708
TI  - Immunogenetics of viral infections.
AB  - The HLA class I and II genes encode molecules that lie at the heart of the
      acquired immune response against infectious diseases. Associations between these
      polymorphic loci and genetically complex infectious diseases have been
      historically elusive, in contrast to the more obvious HLA associations with
      autoimmune diseases. High resolution molecular typing of large, clinically well
      defined cohorts has begun to uncover evidence for the influence of HLA diversity
      on diseases of viral etiology, such as those caused by HIV-1, hepatitis B virus,
      hepatitis C virus and human papilloma virus. Combinations of HLA and KIR also
      appear to affect outcome to viral infection, supporting a role for HLA class I
      diversity in the innate immune response in addition to the acquired immune
      response.

PMID- 16084709
TI  - Extending options for highly sensitized patients to receive a suitable kidney
      graft.
AB  - Highly sensitized patients (anti-HLA) on the kidney waiting list wait longer for
      a suitable crossmatch negative organ. At the moment there are two strategies to
      enhance transplantation of these patients. One approach is the determination of
      acceptable HLA mismatches and application of this knowledge for the selection of
      crossmatch negative donors, and the second is the desensitization of patients
      with intravenous immunoglobulin-based protocols to enable transplantation of an
      organ from a donor towards which antibodies were originally present. Both
      approaches have advantages and disadvantages and are only successful in a
      proportion of the patients. The optimal solution is an integrated strategy
      whereby desensitization is used for those patients for whom the acceptable
      mismatch approach is not successful.

PMID- 16084710
TI  - Transplantation: changing dogmas in clinical transplantation immunology.

PMID- 16084711
TI  - The aging innate immune system.
AB  - Advanced age is associated with a breakdown of the epithelial barriers of the
      skin, lung and gastrointestinal tract, which enables invasion of delicate mucosal
      tissues by pathogenic organisms. Thus, there is an increased challenge for the
      innate immune system in aged subjects, as the portal of pathogen entry becomes
      more readily disturbed. Because of the number of aging baby boomers and the added
      environmental stresses that bombard the immune system on a daily basis, gaining
      an understanding of the functional integrity of the innate immune system in aged
      subjects is of paramount importance. Evidence suggests that macrophages play a
      central role in both innate and adaptive immune responses. Intrinsic, as well as
      extrinsic (environmental), factors dictate macrophage function. In aged subjects,
      the influence of extrinsic factors becomes increasingly more important. This may
      override the innate immune balance--pro- versus anti-inflammatory signals--thus
      yielding an inappropriate (either inadequate or overabundant) response when the
      system is challenged.

PMID- 16084712
TI  - Fetal-maternal microchimerism: impact on hematopoietic stem cell transplantation.
AB  - Reciprocal cell traffic between mother and fetus during pregnancy gives rise to
      postpartum fetal-maternal lymphohematopoietic microchimerism, which is frequently
      detected in blood or tissue from healthy individuals. Although such
      microchimerism has been implicated in the pathogenesis of autoimmune diseases and
      tissue repair, recent clinical experiences have suggested the association of
      microchimerism with acquired immunologic hyporesponsiveness to non-inherited
      maternal HLA antigens (NIMAs) or inherited paternal HLA antigens (IPAs); T cell
      replete HLA-haploidentical hematopoietic stem cell transplantation from a
      microchimeric IPA/NIMA-mismatched donor confers relatively lower incidence of
      severe graft-versus-host disease. The underlying mechanisms by which fetal
      maternal microchimerism contributes to IPA/NIMA-specific tolerance are still
      elusive, although emerging experimental evidence suggests an involvement of the
      central deletion of IPA/NIMA-reactive T cells, the induction of peripheral
      regulatory T cells, and affinity-dependent modulation of NIMA-reactive B cells.

PMID- 16084713
TI  - Designing a purification process for chromium-, copper- and arsenic-contaminated
      wood.
AB  - The disposal of chromated copper arsenate (CCA)-treated wood is becoming a
      serious problem in many countries due to increasing levels of contamination by
      the hazardous elements, chromium, copper and arsenic. The present experiment was
      conducted as a preliminary step toward one-step solvent extraction of CCA-treated
      wood. Because chromium, copper and arsenic have different chemical
      characteristics, it is best to consider them separately prior to designing a one
      step extraction process. As a basis, various two-step extraction processes were
      first designed and tested experimentally to determine feasibility. Among these
      combinations, the treatment combining oxalic acid as the 1st step and a sodium
      oxalate solution under acidic conditions (pH 3.2) as the 2nd step was found to be
      an effective way of extracting CCA elements from treated wood. Extraction
      efficiency reached 100% for arsenic and chromium and 95.8% for copper after a 3-h
      sodium oxalate treatment, following a 1-h pre-extraction process with oxalic
      acid. On the other hand, the same combination under alkaline conditions (pH 11.2)
      during the 2nd step was ineffective for copper removal, indicating that pH plays
      an important role in complexation with sodium oxalate solution. The present
      results suggest that the extraction of CCA elements using a combination of oxalic
      acid and acidic sodium oxalate solution is a promising basis for application to a
      one-step extraction method.

PMID- 16084714
TI  - Human neuroblastoma (SH-SY5Y) cell culture and differentiation in 3-D collagen
      hydrogels for cell-based biosensing.
AB  - Cell-based three-dimensional systems are desirable in the field of high
      throughput screening assays due to their potential similarity to in vivo
      environment. We have used SH-SY5Y human neuroblastoma cells cultured in 3-D
      collagen hydrogel, confocal microscopy and immunofluorescence staining, to assess
      the merit of the system as a functional, cell-based biosensor. Our results show
      differences between 2-D and 3-D resting membrane potential development profile
      upon differentiation. There was no statistically significant difference in SH
      SY5Y proliferation rate between 2-D monolayer and 3-D collagen culture formats. A
      large percentage of cells (2-D, 91.30% and 3-D, 84.93%) did not develop resting
      membrane potential value equal to or lower than -40 mV; instead cells exhibited a
      heterogeneous resting membrane potential distribution. In response to high K(+)
      (50 mM) depolarization, 3-D cells were less responsive in terms of increase in
      intracellular Ca(2+), in comparison to 2-D cells, supporting the hypothesis that
      2-D cell calcium dynamics may be exaggerated. L-Type Ca(2+) expression levels
      based on staining results was inconsistent with Bay K 8644 channel activation
      results, strongly suggesting that either the majority of the channels were non
      functional or could not be activated by Bay K 8644. In general, the results in
      this study confirm the depolarization-induced differences in intracellular
      calcium release when cultured using a 2-D versus a 3-D matrix.

PMID- 16084715
TI  - Bacterial sensors based on Acidithiobacillus ferrooxidans Part II. Cr(VI)
      determination.
AB  - The aerobic acidophilic bacterium Acidithiobacillus ferrooxidans oxidizes Fe(2+)
      and S(2)O(3)(2-) ions by consuming oxygen. An amperometric biosensor was designed
      including an oxygen probe as transducer and a recognition element immobilized by
      a suitable home-made membrane. This biosensor was used for the indirect
      amperometric determination of Cr(2)O(7)(2-) ions owing to methods based on a
      mediator (Fe(2+)) or titration. Using the mediator, the biosensor response versus
      Cr(2)O(7)(2-) was linear up to 0.4 mmol L(-1), with a response time of,
      respectively, 51 s (2 x 10(-5) mol L(-1) Cr(2)O(7)(2-)) and 61 s (6 x 10(-5) mol
      L(-1) Cr(2)O(7)(2-)). The method sensitivity was 816 microA L mol(-1). Response
      time and measurement sensitivity depended on membrane material and technique for
      biomass immobilization. For example, their values were 90 s-200 microA L mol(-1)
      when using a glass-felt membrane and 540 s-4.95 microA L mol(-1) with a carbon
      felt one to determine a concentration of 2 x 10(-5) mol L(-1) Cr(2)O(7)(2-). For
      the titration method, the biosensor is used to determine the equivalence point.
      The relative error of quantitative analysis was lower than 5%.

PMID- 16084716
TI  - How to make pancreatic beta cells--prospects for cell therapy in diabetes.
AB  - One promising approach for the cure of diabetes is the replacement of lost
      insulin-expressing beta cells by cell or regenerative therapy. The recent
      development of an effective islet transplantation procedure has focused attention
      on the limiting supply of beta cells. Various sources for new beta cells are
      therefore being considered, including embryonic stem cells, adult stem cells and
      transdifferentiation of certain types of differentiated cells, so far with
      limited success. The major physiological mechanism for adult beta cell formation
      was recently shown to be beta cell proliferation. This finding underscores the
      potential use of terminally differentiated beta cells as a starting material for
      enhancement of beta cell mass.

PMID- 16084717
TI  - Anthocyans from fruits and vegetables--does bright colour signal cancer
      chemopreventive activity?
AB  - Consumption of fruits and berries has been associated with decreased risk of
      developing cancer. The most abundant flavonoid constituents of fruits and berries
      are anthocyans (i.e. anthocyanins, glycosides, and their aglycons,
      anthocyanidins) that cause intense colouration. In this review, we describe
      epidemiological evidence hinting at the cancer preventive activity of anthocyan
      containing foods in humans, results of chemoprevention studies in rodent models
      with anthocyans or anthocyan-containing fruit/vegetable extracts, and
      pharmacological properties of anthocyans. Anthocyanidins have been shown to
      inhibit malignant cell survival and confound many oncogenic signalling events in
      the 10(-6)-10(-4) M concentration range. Studies of the pharmacokinetics of
      anthocyanins after their consumption as single agents, anthocyanin mixtures or
      berry extracts suggest that anthocyanins reach levels of 10(-8)-10(-7) M in human
      blood. It is unclear whether such concentrations are sufficient to explain
      anticarcinogenic effects, and whether anthocyanins exert chemopreventive efficacy
      themselves, or if they need to undergo hydrolysis to their aglyconic
      counterparts. The currently available literature provides tantalising hints of
      the potential usefulness of anthocyans or anthocyan mixtures as cancer
      chemopreventive interventions. Nevertheless further studies are necessary to help
      adjudge the propitiousness of their clinical development.

PMID- 16084718
TI  - How good are rodent models of carcinogenesis in predicting efficacy in humans? A
      systematic review and meta-analysis of colon chemoprevention in rats, mice and
      men.
AB  - Tumours in rodent and human colon share many histological and genetic features.
      To know if rodent models of colon carcinogenesis are good predictors of
      chemopreventive efficacy in humans, we conducted a meta-analysis of aspirin, beta
      carotene, calcium, and wheat bran studies. Controlled intervention studies of
      adenoma recurrence in human volunteers were compared with chemoprevention studies
      of carcinogen-induced tumours in rats, and of polyps in Min (Apc(+/-)) mice: 6714
      volunteers, 3911 rats and 458 mice were included in the meta-analyses. Difference
      between models was small since most global relative risks were between 0.76 and
      1.00. A closer look showed that carcinogen-induced rat studies matched human
      trials for aspirin, calcium, carotene, and were compatible for wheat bran. Min
      mice results were compatible with human results for aspirin, but discordant for
      calcium and wheat bran (no carotene study). These few results suggest that rodent
      models roughly predict effect in humans, but the prediction is not accurate for
      all agents. Based on three cases only, the carcinogen-induced rat model seems
      better than the Min mouse model. However, rodent studies are useful to screen
      potential chemopreventive agents, and to study mechanisms of carcinogenesis and
      chemoprevention.

PMID- 16084719
TI  - Night work and breast cancer risk: a systematic review and meta-analysis.
AB  - The association between occupations that involve night shift work (a surrogate
      for exposure to light at night with subsequent melatonin suppression) and breast
      cancer risk is uncertain. We therefore conducted a systematic review and meta
      analysis of observational studies to assess the effects of night work on breast
      cancer risk. Data sources were MEDLINE from January 1960 to January 2005, experts
      in the field, bibliographies, and abstracts. Search terms included night work
      terms, flight personnel terms, cancer terms, and risk terms. Independent data
      extraction by two authors using standardised forms was performed. The method of
      DerSimonian and Laird was used to derive combined estimates and Egger's; and Begg
      and Mazumdar's tests for publication bias were conducted. Based on 13 studies,
      including seven studies of airline cabin crew and six studies of other night
      shift workers, the aggregate estimate for all studies combined was 1.48 (95% CI,
      1.36-1.61), with a similar significant elevation of breast cancer risk among
      female airline cabin crew (standardised incidence ratio (SIR), 1.44; 95% CI, 1.26
      1.65), and female night workers (relative risk (RR), 1.51; 95% CI, 1.36-1.68)
      separately. We found some evidence suggesting confounding due to incomplete
      adjustment for breast cancer risk factors, with smaller effects in the studies
      that more completely adjusted for reproductive history and other confounding
      factors. Egger's and Begg and Mazumdar's tests for publication bias showed no
      significant asymmetry (P>0.05). Studies on night shift work and breast cancer
      risk collectively show an increased breast cancer risk among women. Publication
      bias is unlikely to have influenced the results.

PMID- 16084720
TI  - Acetylenic TACE inhibitors. Part 2: SAR of six-membered cyclic sulfonamide
      hydroxamates.
AB  - The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a
      butynyloxy P1' group was explored. In particular, compound 5k has excellent in
      vitro potency against TACE enzyme and in cells, and oral activity in an in vivo
      model of TNF-alpha production and a collagen-induced arthritis model.

PMID- 16084721
TI  - Isolation, structure elucidation, preparation, and biological properties of
      neolambertellin.
AB  - Neolambertellin (4), a novel biosynthetic congener of lambertellol and
      lambertellin, was isolated. The structure was confirmed by successful preparation
      from lambertellol A, which involves a rearrangement of spiro-butenolide moiety.

PMID- 16084722
TI  - Boro-norleucine as a P1 residue for the design of selective and potent DPP7
      inhibitors.
AB  - Dipeptide-based inhibitors with C-substituted (alkyl or aminoalkyl) alpha-amino
      acids in the P2 position and boro-norleucine (boro-Nle) in the P1 position were
      synthesized. Relative to boro-proline, boro-Nle as a P1 residue was shown able to
      significantly dial out DPP4, FAP, DPP8, and DPP9 activity. Dab-boro-Nle (4g)
      proved to be the most selective and potent DPP7 inhibitor with a DPP7 IC50 value
      of 480 pM.

PMID- 16084723
TI  - DNA electroporation in vivo targets mature fibres in dystrophic mdx muscle.
AB  - Non-viral gene transfer into skeletal muscle is enhanced by electroporation and
      myotoxin preconditioning of muscle following plasmid injection. We investigated
      in vivo delivery of naked DNA to mdx mouse muscle, utilising enhanced green
      fluorescent protein reporter vector (pEGFP) and a corrective nucleic acid to
      promote targeted corrective gene conversion at the mutant mdx mouse dystrophin
      (DMDmdx) locus. Electroporation, myoablation with bupivacaine and a combined
      protocol, were applied to mdx muscle. We report up to 90% EGFP expression in
      electroporated mdx tibialis anterior muscle. Muscles preconditioned with
      bupivacaine showed low transgene expression with or without EP. Single EGFP+ve
      muscle fibre explants showed EGFP expression in mature fibres in preference to
      satellite cells. We observed a two-fold increase (P<0.005; t) in dystrophin
      protein, accompanied by wild-type (wt) DMD transcript in muscles injected with
      corrective nucleic acid over contralateral saline-injected TAs. By targeting the
      muscle fibres in preference to the satellite cells, plasmid-bourne transgenes
      delivered to dystrophic muscle will not penetrate the regenerative component of
      muscle. Whether in the context of targeted corrective gene conversion or
      therapeutic non-viral transgenes, under these conditions periodic re
      administration will be required to promote phenotypic benefits in dystrophic
      muscle.

PMID- 16084724
TI  - Analysis of the kinesin superfamily: insights into structure and function.
AB  - Kinesin superfamily proteins (KIFs) are key players or 'hub' proteins in the
      intracellular transport system, which is essential for cellular function and
      morphology. The KIF superfamily is also the first large protein family in mammals
      whose constituents have been completely identified and confirmed both in silico
      and in vivo. Numerous studies have revealed the structures and functions of
      individual family members; however, the relationships between members or a
      perspective of the whole superfamily structure until recently remained elusive.
      Here, we present a comprehensive summary based on a large, systematic
      phylogenetic analysis of the kinesin superfamily. All available sequences in
      public databases, including genomic information from all model organisms, were
      analyzed to yield the most complete phylogenetic kinesin tree thus far,
      comprising 14 families. This comprehensive classification builds on the recently
      proposed standardized nomenclature for kinesins and allows systematic analysis of
      the structural and functional relationships within the kinesin superfamily.

PMID- 16084725
TI  - Structure-activity studies of uptake and phototoxicity with heavy-chalcogen
      analogues of tetramethylrosamine in vitro in chemosensitive and multidrug
      resistant cells.
AB  - Several thio and seleno analogues of tetramethylrosamine (TMR) were prepared.
      Thio derivatives of TMR have absorption maxima near 570 nm, while seleno
      derivatives of TMR have absorption maxima near 580 nm. The 3- or 4-N,N
      dimethylaminophenyl substituent in the 9-position greatly increases internal
      conversion, which lowers quantum yields for fluorescence and the generation of
      singlet oxygen. Thio and seleno analogues of TMR are effective photosensitizers
      against chemosensitive AUXB1 cells in vitro and against multidrug-resistant
      CR1R12 cells in vitro, which have been treated with verapamil. The CR1R12 cells
      accumulated significantly lower concentrations of the photosensitizers relative
      to the AUXB1 cells presumably due to the expression of P-glycoprotein (Pgp) in
      the CR1R12 cells. Following treatment with 5 x 10(-5) M verapamil, the uptake in
      CR1R12 cells of several fluorescent thio analogues of TMR is comparable to that
      observed for the chemosensitive AUXB1 cells.

PMID- 16084726
TI  - Preparation and anti-inflammatory activities of diarylheptanoid and
      diarylheptylamine analogs.
AB  - Seven diarylheptylamine (12a-g) and four diarylheptanoid analogs (3-5, 9),
      structurally related to the natural anti-inflammatory agent oregonin (1), have
      been prepared from curcumin (2) for evaluation of their activity against the
      expression of iNOS and COX-2. Diarylheptylamine 12b and diarylheptanoid analogs
      can inhibit iNOS and COX-2 responses of LPS, although less potently than 1. These
      compounds, however, possess stronger potency than 1 against COX-2-derived PGE2
      formation, of which hexahydrocurcumin (4) is the most potent one with an IC50
      value of 0.7 microM.

PMID- 16084727
TI  - Water-soluble chitosan derivatives as a BACE1 inhibitor.
AB  - BACE1 (the beta-site APP-cleaving enzyme) inhibitory activities of water-soluble
      chitosan derivatives substituted with aminoethyl, dimethylaminoethyl and
      diethylaminoethyl groups were investigated. AE-chitosan (90%) prepared from 90%
      deacetylated chitosan showed the strongest BACE1 inhibitory activity than those
      of other derivatives. The inhibitory pattern was found to be non-competitive by
      Dixon plot, and the value of the inhibition constant (K(i)) was 85 microg/mL.

PMID- 16084728
TI  - New neoclerodane diterpenoids isolated from the leaves of Salvia divinorum and
      their binding affinities for human kappa opioid receptors.
AB  - Bioactivity-guided fractionation of the leaves of Salvia divinorum has resulted
      in the isolation of three new neoclerodane diterpenoids: divinatorin D (1),
      divinatorin E (2), and salvinorin G (3), together with 10 known terpenoids,
      divinatorin C (4), hardwickiic acid (5), salvinorin-A (6), -B (7), -C (8), -D
      (9), -E (10), and -F (11), presqualene alcohol (12), and (E)-phytol (13). The
      structures of these three new compounds were characterized by spectroscopic
      methods. All these compounds were evaluated for their binding affinities to the
      human kappa opioid receptors. In comparison with divinatorin D (1), divinatorin E
      (2), and salvinorin G (3), salvinorin A (6) is still the most potent kappa
      agonist.

PMID- 16084729
TI  - Core-modified porphyrins. Part 5: Electronic effects on photophysical and
      biological properties in vitro.
AB  - 21,23-Dithiaporphyrins 2-11 were prepared as analogues of 5,20-diphenyl-10,15
      bis(4-carboxylatomethoxy)phenyl-21,23-dithiaporphyrin 1 to examine the impact of
      electronic properties at the 5- and 20-meso-positions. The effects of the
      electronic properties at the meso-rings were not significant with respect to
      absorption spectra, quantum yields for the generation of singlet oxygen and for
      fluorescence. While some differences were noted in the n-octanol/pH 7.4 buffer
      partition coefficient, log D(7.4), among the compounds, log D(7.4) did not
      critically influence the cellular uptake or phototoxicity. None of the
      dithiaporphyrins 1-11 displayed dark toxicity at concentrations up to 1 x 10(-5)
      M. Once irradiated with 5 J cm(-2) of 350-750 nm light, five porphyrins 2, 3, 5,
      6, and 8 killed over 80% of R3230AC rat mammary adenocarcinoma cells at 5 x 10(
      7) M photosensitizer. Among these five, compound 3 bearing 5-phenyl and 20-(4
      fluorophenyl) substituents was the most potent photosensitizer toward R3230AC
      cells showing 67% cell kill at 1 x 10(-7) M 3. Bulky substituents at the 5- and
      20-positions gave photosensitizers with minimal phototoxicity.

PMID- 16084730
TI  - Truncated wild-type SOD1 and FALS-linked mutant SOD1 cause neural cell death in
      the chick embryo spinal cord.
AB  - Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial
      (FALS), and approximately 25% of FALS cases are caused by mutations in superoxide
      dismutase-1 (SOD1). Mutant (MT) SOD1 kills motor neurons because of the mutant
      protein's toxicity; however, the basis for toxicity is unknown. We electroporated
      wild-type (WT), truncated WT or MTSOD1 expression constructs into the chick
      embryo spinal cord. MTSOD1 and truncated WTSOD1 (as small as 36 amino acid
      residues in length) aggregated in the cytoplasm of cells and caused cell death.
      These results suggest that MTSOD1 and truncated WTSOD1 lead to neural cell death
      because of misfolding, and that SOD1 peptides, possibly as a result of
      proteolytic digestion of MTSOD, play a role in FALS pathogenesis. Electroporation
      of the chick embryo spinal cord is a useful system in which to investigate
      neurodegenerative diseases because it provides efficient delivery of genes into
      neural cells in situ within a living organism.

PMID- 16084731
TI  - Amygdaloid kindled seizures can induce functional and pathological changes in
      thymus of rat: role of the sympathetic nervous system.
AB  - The present study sought to determine the effects of long-term kindled seizures
      of the basal amygdala upon immune function in rat, utilizing the thymus, as a
      principal target for study. Histopathology from kindled Sprague-Dawley rats
      revealed the presence of epithelial cell thymoma in 70% of these rats. The
      results revealed an increased rate of apoptosis and proliferation in thymic
      epithelial cells. Analysis of thymocytes indicated a decrease in the ratio of CD4
      to CD8 positive T cells and reduced proliferative response to T-cell mitogens. To
      determine whether these effects were mediated through the sympathetic nervous
      system, animals were treated with guanethidine, which blocked the development of
      epithelial cell thymomas, while mifepristone treatment, employed to determine the
      possible role of the hypothalamic-pituitary axis, was ineffective in attenuating
      thymoma development. Thus, the present study demonstrated that functional and
      pathological changes in the thymus during kindled seizures are mediated through
      the sympathetic nervous system.

PMID- 16084732
TI  - Functional reinnervation from remaining DA terminals induced by GDNF lentivirus
      in a rat model of early Parkinson's disease.
AB  - Glial cell-line derived neurotrophic factor (GDNF) is a good candidate agent for
      restoring functional reinnervation and/or neuroprotection of dopamine (DA)
      nigrostriatal system and thus for the treatment of Parkinson's disease (PD).
      Viral delivery is currently the most likely in vivo strategy for delivery of the
      therapeutic protein into the brain for treatment of neurological diseases.
      However, one of the important unresolved issues for this strategy is the
      threshold number of DA nigral neurons and/or of striatal DA terminals necessary
      for optimal benefit from GDNF therapy. In this study, we examined the
      intrastriatal neurotrophic effects of long-term GDNF delivery using a lentiviral
      vector in a new rat model of early PD. Lenti-GDNF was injected into the striatum
      4 weeks after partial substantia nigra pars compacta 6-hydroxydopamine-induced
      lesion. Striatal denervation was evaluated by assessing tyrosine hydroxylase
      positive DA fiber density and corroborated by testing motor deficit by means of a
      staircase test. GDNF treatment restored complete striatal DA innervation in the
      previously denervated area and this was associated with significant behavioral
      improvements.

PMID- 16084733
TI  - Structural and functional MRI following 4-aminopyridine-induced seizures: a
      comparative imaging and anatomical study.
AB  - Structural and functional MRI was used in conjunction with computerized electron
      microscopy morphometry to study changes 2 h, 24 h and 3 days after 4
      aminopyridine-induced seizures lasting 2 h in rats. T2 (relaxation time) values
      showed changes throughout the cerebral cortex, hippocampus, amygdala and medial
      thalamus, with a different temporal progression, showing a complete recovery only
      after 3 days. Two hours after seizures, the apparent diffusion coefficient was
      decreased throughout the brain compared to control animals, and a further
      decrease was evident 24 h after seizures. This was followed by a complete
      recovery at 3 days post-seizures. Functional MRI was performed using regional
      cerebral blood volume (rCBV) maps. The rCBV was increased shortly after
      convulsions (2 h) in all structures investigated, with a significant return to
      baseline values in the parietal cortex and hippocampus, but not in the medial
      thalamic nuclei, 24 h after seizure onset. No rCBV alterations were detected 3
      days after seizures. Electron microscopy of tissue samples of parietal neocortex
      and hippocampus revealed prominent astrocytic swelling 2 h post-convulsions which
      decreased thereafter gradually. In conclusion, this experiment reports for the
      first time structural and functional brain alterations, lasting several hours, in
      4-aminopyridine-treated rats after seizure onset. MRI approach combined with
      histological and ultrastructural analysis provided a clarification of the
      mechanisms involved in the brain acute response to ictal activity.

PMID- 16084734
TI  - Degeneration of respiratory motor neurons in the SOD1 G93A transgenic rat model
      of ALS.
AB  - The transgenic mutant superoxide dismutase (SOD1) mice and rats have been
      important tools in attempting to understand motor neuron pathology and
      degeneration but the mechanism behind death in this model has not been studied.
      We studied the electrophysiologic and pathologic properties of the cervical motor
      neurons and phrenic nerves in mutant SOD1 rats and demonstrated motor neuron
      loss, progressive reduction of phrenic nerve compound muscle action potential
      amplitudes, phrenic nerve fiber loss, and diaphragm atrophy suggesting
      respiratory insufficiency as a significant contributing factor leading to SOD1
      rat death. Unlike previous observations suggesting that a dying-back process may
      be occurring in the mouse model of the disease, we did not observe differences
      between proximal and distal axon loss in phrenic nerves of SOD1 rats. This may
      reflect a unique feature of respiratory motor neuron biology or may be related to
      the relatively rapid course of decline in the rat model when compared with the
      mouse SOD1 model. Significant motor neuron loss was also noted in the lumbosacral
      spinal cord with relative sparing of motor neurons in the cranial nuclei. Taken
      together, these data suggest that respiratory motor neuron loss results in
      significant electrophysiologic changes and diaphragmatic atrophy. These changes
      may play a significant role resulting in death of these animals.

PMID- 16084735
TI  - Use of comprehensive geriatric assessment in older cancer patients:
      recommendations from the task force on CGA of the International Society of
      Geriatric Oncology (SIOG).
AB  - BACKGROUND: As more and more cancers occur in elderly people, oncologists are
      increasingly confronted with the necessity of integrating geriatric parameters in
      the treatment of their patients. METHODS: The International Society of Geriatric
      Oncology (SIOG) created a task force to review the evidence on the use of a
      comprehensive geriatric assessment (CGA) in cancer patients. A systematic review
      of the evidence was conducted. RESULTS: Several biological and clinical
      correlates of aging have been identified. Their relative weight and clinical
      usefulness is still poorly defined. There is strong evidence that a CGA detects
      many problems missed by a regular assessment in general geriatric and in cancer
      patients. There is also strong evidence that a CGA improves function and reduces
      hospitalization in the elderly. There is heterogeneous evidence that it improves
      survival and that it is cost-effective. There is corroborative evidence from a
      few studies conducted in cancer patients. Screening tools exist and were
      successfully used in settings such as the emergency room, but globally were
      poorly tested. The article contains recommendations for the use of CGA in
      research and clinical care for older cancer patients. CONCLUSIONS: A CGA, with or
      without screening, and with follow-up, should be used in older cancer patients,
      in order to detect unaddressed problems, improve their functional status, and
      possibly their survival. The task force cannot recommend any specific tool or
      approach above others at this point and general geriatric experience should be
      used.

PMID- 16084736
TI  - Validation of the inactivant binary ethylenimine for inactivating rabies virus
      for veterinary rabies vaccine production.
AB  - The rabies vaccine is produced by inactivation of rabies virus propagated on
      BHK21 cells. In the rabies inactivation process, BEI is added at a final
      concentration of 1.6 mM to the viral harvest at 37 degrees C, followed by a
      second dose of BEI at 24 h post-inactivation. Inactivation was confirmed by the
      mice innocuity test and tissue culture amplification test as per B.P (Vet) 2004.
      Validation of test procedure is essential as per cGMP requirement. The dose of
      BEI was validated by using lower and higher concentrations of BEI in inactivation
      process. The study indicated that BEI at a lower concentration (0.4 mM) was able
      to inactivate the rabies virus within 30 h and the routine concentration (1.6 mM)
      of BEI is effective in inactivating rabies virus within 18 h. The amplification
      test used for confirming the inactivation of the live virus was validated by
      spiking the sample with different dilutions of pretitrated live rabies virus. The
      test revealed that the amplification method is sensitive to detect live rabies
      virus if present in the inactivated sample. The validation of BEI as an
      inactivant and the amplification test are discussed.

PMID- 16084737
TI  - Transcallosal inhibition in chronic subcortical stroke.
AB  - Movements of the paretic hand in patients with chronic subcortical stroke are
      associated with high interhemispheric inhibition (IHI) targeting the motor cortex
      in the lesioned hemisphere relative to healthy controls. The purpose of this
      investigation was to determine whether this abnormality also involves IHI
      operating during movements of the non-paretic hand. Here, we studied IHI in the
      process of generation of voluntary index finger movements by the paretic and non
      paretic hands in a simple reaction time paradigm in a group of patients with
      chronic subcortical stroke. With movements of the non-paretic index finger, IHI
      targeting the contralateral primary motor cortex ((c)M1) decreased progressively
      to turn into facilitation at around movement onset, similar to healthy controls.
      In contrast, movements of the paretic index finger resulted in significantly
      deeper inhibition at all premovement timings relative to the non-paretic hand. In
      conclusion, these results document a deeper premovement IHI with paretic than non
      paretic hand movements of patients with chronic subcortical stroke, a possible
      mechanism underlying deficits in motor control.

PMID- 16084738
TI  - Diffusion tensor imaging in chronic head injury survivors: correlations with
      learning and memory indices.
AB  - Diffusion tensor imaging (DTI) provides a unique insight into the cellular
      integrity of the brain. While conventional magnetic resonance imaging
      underestimates the extent of pathology following closed head injury, diffusion
      weighted imaging has been shown to more accurately delineate the extent of
      cerebral damage. There have only been a few case studies of DTI in chronic head
      injury survivors. This study used DTI to investigate changes in anisotropy and
      diffusivity in survivors of head injury at least 6 months after their injury. The
      relationship between cognition and diffusion abnormality was also investigated.
      The voxel-based analysis revealed significant bilateral decreases in anisotropy,
      in major white matter tracts and association fibers in the temporal, frontal,
      parietal and occipital lobes. Statistically significant increases in diffusivity
      were also found in widespread areas of the cortex. A significant positive
      correlation was found between diffusivity and impairment of learning and memory
      in the left posterior cingulate, left hippocampal formation and left temporal,
      frontal and occipital cortex. The common pattern of abnormality despite
      heterogeneous injury mechanism and lesion location in the group suggests that
      these cellular changes reflect secondary insults. The importance of diffusion
      abnormalities in head injury outcome is emphasized by the significant correlation
      between a learning and memory index and diffusivity in areas known to subserve
      this cognitive function.

PMID- 16084739
TI  - Incidental effects of emotional valence in single word processing: an fMRI study.
AB  - The present study aimed at identifying the neural responses associated with the
      incidental processing of the emotional valence of single words using event
      related functional magnetic resonance imaging (fMRI). Twenty right-handed
      participants performed a visual lexical decision task, discriminating between
      nouns and orthographically and phonologically legal nonwords. Positive, neutral
      and negative word categories were matched for frequency, number and frequency of
      orthographic neighbors, number of letters and imageability. Response times and
      accuracy data differed significantly between positive and neutral, and positive
      and negative words respectively, thus, replicating the findings of a pilot study.
      Words showed distributed, mainly left hemisphere activations, indicating
      involvement of a neural network responsible for semantic word knowledge. The
      neuroimaging data further revealed areas in left orbitofrontal gyrus and
      bilateral inferior frontal gyrus with greater activation to emotional than to
      neutral words. These brain regions are known to be involved in processing
      semantic and emotional information. Furthermore, distinct activations associated
      with positive words were observed in bilateral middle temporal and superior
      frontal gyrus, known to support semantic retrieval, and a distributed network,
      namely anterior and posterior cingulate gyrus, lingual gyrus and hippocampus when
      comparing positive and negative words. The latter areas were previously
      associated with explicit and not incidental processing of the emotional meaning
      of words and emotional memory retrieval. Thus, the results are discussed in
      relation to models of processing semantic and episodic emotional information.

PMID- 16084740
TI  - Enduring representational plasticity after somatosensory stimulation.
AB  - Somatosensory stimulation (SS), leading to increases in motor cortical
      excitability, influences motor performance in patients with brain lesions like
      stroke. The mechanisms by which SS modulates motor function are incompletely
      understood. Here, we used functional magnetic resonance imaging (fMRI, blood
      oxygenation-level-dependent (BOLD), and perfusion imagings simultaneously
      acquired in a 3 T magnet) to assess the effects of SS on thumb-movement-related
      activation in three regions of interest (ROI) in the motor network: primary motor
      cortex (M1), primary somatosensory cortex (S1), and dorsal premotor cortex (PMd)
      in healthy volunteers. Scans were obtained in different sessions before and after
      2-h electrical stimulation applied to the median nerve at the wrist (MNS), to the
      skin overlying the shoulder deltoid muscle (DMS), and in the absence of
      stimulation (NOSTIM) in a counterbalanced design. We found that baseline
      perfusion intensity was comparable within and across sessions. MNS but not DMS
      nor NOSTIM led to an increase in signal intensity and number of voxels activated
      by performance of median nerve-innervated thumb movements in M1, S1, and PMd for
      up to 60 min. Task-related fMRI activation changes were most prominent in M1
      followed by S1 and to a lesser extent in PMd. MNS elicited a displacement of the
      center of gravity for the thumb movement representation towards the other finger
      representations within S1. These results indicate that MNS leads to an expansion
      of the thumb representation towards other finger representations within S1, a
      form of plasticity that may underlie the influence of SS on motor cortical
      function, possibly supporting beneficial effects on motor control.

PMID- 16084741
TI  - Neuroanatomical differences between mouse strains as shown by high-resolution 3D
      MRI.
AB  - The search for new mouse models of human disease requires a sensitive metric to
      make three-dimensional (3D) anatomical comparisons in a rapid and quantifiable
      manner. This is especially true in the brain, where changes in complex shapes
      such as the hippocampus and ventricles are difficult to assess with 2D histology.
      Here, we report that the 3D neuroanatomy of three strains of mice (129S1/SvImJ,
      C57/Bl6, and CD1) is significantly different from one another. Using image co
      registration, we 'morphed' together nine brains of each strain scanned by
      magnetic resonance imaging at (60 microm)3 resolution to synthesize an average
      image. We applied three methods of comparison. First, we used visual inspection
      and graphically examined the standard deviation of the variability in each
      strain. Second, we annotated 42 neural structures and compared their volumes
      across the strains. Third, we assessed significant local deviations in volume and
      displacement between the two inbred strains, independent of prior anatomical
      knowledge.

PMID- 16084742
TI  - Frequency of provocative factors in epileptic patients admitted for seizures: a
      prospective study in Singapore.
AB  - Intractable epilepsy is commonly believed to be the main cause of uncontrolled
      seizures and hospitalization in epileptic patients. We study frequency and types
      of potential provocative factors in epileptic patients admitted with seizures,
      and suggest methods to decrease seizure occurrence and hospitalization. Over 6
      months we prospectively studied all epileptic patients hospitalized for seizures.
      A structured interview and laboratory investigations were used to determine type
      and number of potential seizure precipitants. Precipitants thought to be
      avoidable through actions taken by the patient or physicians were termed
      potentially preventable provocative factors (PPPF). Patients' awareness and
      knowledge of seizure precipitants were also assessed. Three quarters of all
      seizures leading to admission were associated with PPPF, the commonest being non
      compliance (71%), sub-therapeutic doses of antiepileptic drugs (26%) and sleep
      deprivation (9%). Only one patient had intractable epilepsy. Patients' knowledge
      of seizure precipitants was poor. The majority of hospital admissions for
      seizures in epileptic patients are associated with potentially preventable causes
      amenable to education programmes. Patient education involving epilepsy nurse
      educators may play an important role in decreasing seizure occurrence and
      possibly unnecessary hospital admissions.

PMID- 16084743
TI  - Genetic network during neural crest induction: from cell specification to cell
      survival.
AB  - The concerted action of extracellular signals such as BMP, Wnt, FGF, RA and Notch
      activate a genetic program required to transform a naive ectodermal cell into a
      neural crest cell. In this review we will analyze the extracellular signals and
      the network of transcription factors that are required for this transformation.
      We will propose the division of this complex network of factors in two main
      steps: an initial cell specification step followed by a maintenance or cell
      survival step.

PMID- 16084744
TI  - Determining a helical protein structure using peptide pixels.
AB  - The residual dipolar coupling-periodicity planarity correlation makes it possible
      to determine peptide plane orientations in regular periodic protein secondary
      structure elements. Each peptide plane orientation represents a "pixel" of
      protein structure, and is expressed in terms of three angles referred to as tilt,
      phase, and pitch angles. In this report, we present the novel "3P" (periodicity,
      planarity, and pixels) method that allows one to determine secondary and tertiary
      structure of alpha-helical proteins. We demonstrate the 3P method by determining
      the structure of domain 1 of the receptor-associated protein (RAP) to a backbone
      accuracy of 1.0 Angstrom using RDCs measured in a single alignment medium,
      together with a minimal number of NOE distance restraints, using a new Xplor-NIH
      module.

PMID- 16084745
TI  - Medical negligence: Can doctors and nurses still rely on the doctrine that they
      know best?
AB  - It is questionable today as to whether doctors know what is in the patient's best
      interest when it comes to delivering health care. This is further highlighted by
      changes in English law where the previously sound Bolam test has come under
      scrutiny as expert witness testimony is being contested in terms of its
      defensibility. Hence the Bolitho case has questioned the authenticity of expert
      knowledge in view of the Bolam test to the extent that opinion amongst expert
      groups may not in fact be based on sound current knowledge. As such this then has
      implications on the outcome of future litigations because expert opinion may well
      be open to scrutiny and logicality. Therefore, this article will discuss the
      development of medical negligence litigation since the inception of the Bolam
      test as a defence in medical law. It will also discuss Lord Woolf's warning to
      medical professionals that the courts would no longer apply a deferential
      'Doctors knows best' doctrine in negligence cases. It will particularly look at
      the Bolam test and discuss whether this standing alone is a good enough defence
      in medical negligence.

PMID- 16084746
TI  - Sexually transmitted infection and blood-borne virus screening in juvenile
      correctional facilities: a review of the literature and recommendations for
      Australian centres.
AB  - BACKGROUND: Juveniles in custody are disproportionately affected by sexually
      transmitted infections (STI) and blood-borne viruses (BBV) due to high rates of
      risk behaviours. METHODS: A literature review was undertaken with the aim of
      providing evidence-based recommendations on STI/BBV screening in Australian
      juvenile correctional facilities. Relevant research was identified using
      Premedline and Medline databases, followed by a manual search of reference lists
      in relevant articles identified in the database search. A total of 36 relevant
      publications were identified and reviewed. RESULTS: STI/BBV knowledge in
      incarcerated youth is poor and accompanied by high rates of sexual and blood
      borne risk behaviours. The prevalence of these infections is considerable. High
      rates of asymptomatic gonococcal and chlamydial infections exist, which can be
      easily diagnosed on self-collected specimens using new nucleic acid amplification
      technology. HIV infections are rare although continued vigilance is needed in
      view of substantial risk factors for infection. Hepatitis C prevalence is high,
      although much lower than that of adult prisoners, signifying a possible window of
      opportunity for Hepatitis C prevention. Many remain at risk of Hepatitis B, and
      it is important to assess the need for vaccination in this group. CONCLUSION:
      Screening for STI/BBV in incarcerated juveniles is of major public health
      importance and all individuals should be offered screening in conjunction with
      risk-reduction education during their admission to juvenile detention centres.

PMID- 16084747
TI  - Is sudden death with vitamin C deficiency caused by lack of carnitine?
AB  - We investigated the effect of carnitine supplementation during vitamin C (ASC)
      deficiency by measuring the levels of ASC and carnitine in plasma and cardiac
      muscle cells (CMC), and histological analysis with electron microscopy. The
      levels of carnitine were significantly decreased in ASC-deficient rats in plasma
      and the heart than those in the control. In carnitine supplemented ASC-deficient
      rats, a significant increase of carnitine levels were observed in both plasma and
      heart. The number of lipid droplets significantly increased in the ASC-deficient
      rats compared to the control rats, but did not increase in carnitine supplemented
      rats. These results indicate that ASC deficiency causes a generalized
      mitochondrial abnormality and accumulation of lipid droplets in CMC as observed
      in carnitine deficiency, and supplementation of carnitine prevented these changes
      even in the presence of ASC deficiency.

PMID- 16084748
TI  - HPLC-DAD for analysis of different classes of drugs in plasma.
AB  - A solid-phase extraction technique and HPLC-DAD method for drug screening in
      plasma were developed. This analytical method extracts and tests a number of
      drugs of different classes. The method includes; an acidic and basic Solid Phase
      Extraction (SPE) of plasma with C18 cartridges, a gradient elution of a modified
      cyano column with acidic buffer/acetonitrile eluent and a photodiode array
      ultraviolet (UV) detection. The drug screening procedure applied uses retention
      index and UV spectral data for the identification of compounds, may be
      appropriate in particular laboratory settings.

PMID- 16084749
TI  - Exercise therapy for low back pain: a small-scale exploratory survey of current
      physiotherapy practice in the Republic of Ireland acute hospital setting.
AB  - A small-scale exploratory cross-sectional survey investigated the current use of
      a range of exercise therapy approaches for low back pain (LBP) by outpatient
      physiotherapists in the acute hospital setting in the Republic of Ireland, where
      the majority of publicly funded treatment is delivered. Of the 120 postal
      questionnaires distributed to 24 physiotherapy departments, 87 were returned
      (72.5% response rate). The results showed specific spinal stabilization exercises
      were the most popular exercise therapy for acute (39%; n = 35) and chronic (51%;
      n = 48) LBP, followed by the McKenzie approach (acute LBP (ALBP) 35.6%; n = 32:
      chronic LBP (CLBP) 17%; n = 16), and abdominal exercise (ALBP 11.1%; n = 10: CLBP
      9.6%; n = 9). The most popular forms of exercise therapy used by outpatient
      physiotherapists in acute hospital settings in Ireland lack support from evidence
      based clinical guidelines, and further large-scale high quality randomized
      controlled trials of these approaches are warranted. Further research should also
      establish the use of exercise therapy and attitudes to clinical guidelines of
      physiotherapists in other countries and healthcare settings.

PMID- 16084750
TI  - Muscle glutamine depletion in the intensive care unit.
AB  - Glutamine is primarily synthesized in skeletal muscle and enables transfer of
      nitrogen to splanchnic tissues, kidneys and immune system. Discrepancy between
      increasing rates of glutamine utilization at whole body level and relative
      impairment of de novo synthesis in skeletal muscle leads to systemic glutamine
      deficiency and characterizes critical illness. Glutamine depletion at whole body
      level may contribute to gut, liver and immune system disfunctions, whereas its
      intramuscular deficiency may directly contribute to lean body mass loss. Severe
      intramuscular glutamine depletion also develops because of outward transport
      system upregulation, which is not counteracted by increased de novo synthesis.
      The negative impact of systemic glutamine depletion on critically ill patients is
      suggested both by the association between a lower plasma glutamine concentration
      and poor outcome and by a clear clinical benefit after glutamine supplementation.
      Enteral glutamine administration preferentially increases glutamine disposal in
      splanchnic tissues, whereas parenteral supplementation provides glutamine to the
      whole organism. Nonetheless, systemic administration was ineffective in
      preventing muscle depletion, due to a relative inability of skeletal muscle to
      seize glutamine from the bloodstream. Intramuscular glutamine depletion could be
      potentially counteracted by promoting de novo glutamine synthesis with
      pharmacological or nutritional interventions.

PMID- 16084751
TI  - Sequence- and position-dependent tagging protects extracellular-regulated kinase
      3 protein from 26S proteasome-mediated degradation.
AB  - Extracellular-regulated kinase 3, an atypical member of the mitogen-activated
      protein kinase subfamily of extracellular-regulated kinases, was originally
      identified in 1991. Little is known about the biochemical properties, regulation,
      and biological functions of this protein kinase, partially due to the unstable
      nature of endogenous and low ectopical expression level of the protein. Here, we
      report that a single C-terminal c-myc tag increases the half-life of ectopic
      expressed tagged extracellular-regulated kinase 3 approximately four times
      compared to the reported 30 min half-life time for the endogenous protein and
      ectopic expressed extracellular-regulated kinase 3 deprived of its c-myc tag.
      These findings indicate that this C-terminal tag stabilizes the extracellular
      regulated kinase 3. The stabilizing effect of the C-terminal c-myc tag is
      observed in all cell types tested, but is position- and tag sequence-dependent as
      neither N-terminal c-myc tag nor C-terminal HA tag stabilize the protein. The c
      myc tag on extracellular-regulated kinase 3 did not interfere with its kinase
      activity, nor did it abrogate its ability to interacts with its bona fide
      substrate mitogen-activated protein kinase-activated protein kinase 5, indicating
      that tagging did not alter the known biological properties of the protein.
      Stabilization of the tagged extracellular-regulated kinase 3 protein probably
      results from reduced ubiquitination. In conclusion, position and sequence
      specific tagging should provide an easy and useful tool to generate a more stable
      protein that can functionally substitute the endogenous unstable protein. A
      stabilized variant may facilitate studies on the biological role of the protein.

PMID- 16084752
TI  - Eotaxin-3/CCL26 gene expression in intestinal epithelial cells is up-regulated by
      interleukin-4 and interleukin-13 via the signal transducer and activator of
      transcription 6.
AB  - Several inflammatory processes of the bowel are characterized by an accumulation
      of eosinophils at sites of inflammation. The mechanisms that govern mucosal
      infiltration with eosinophils are not fully understood. Eotaxin-3/CCL-26 belongs
      to a family of CC chemokines, which are potent chemoattractants for eosinophils.
      In this study, we hypothesized that intestinal epithelial cells could release
      eotaxin-3. We demonstrate that the T helper 2 type cytokines interleukin-4 or
      interleukin-13 increase eotaxin-3 mRNA levels and eotaxin-3 protein expression in
      the human intestinal epithelial cell lines HT-29 CL.19A and T84 in a dose
      dependent manner. Addition of actinomycin-D prior to interleukin-4/-13
      stimulation led to decreases in eotaxin-3 mRNA levels similar to those observed
      in controls without interleukin-4/-13. Interleukin-4 and interleukin-13 activated
      signal transducer and activator of transcription 6 which was found to bind the
      two canonical signal transducer and activator of transcription 6 binding sites
      located in the eotaxin-3 promoter. Experiments with the eotaxin-3 promoter
      luciferase constructs revealed that the most proximal signal transducer and
      activator of transcription 6 binding site located between positions -62 and -71
      relative to the transcriptional start was necessary for full eotaxin-3 promoter
      activity. Importantly, we present evidence that the signal transducer and
      activator of transcription 6 is necessary and sufficient for interleukin-4 or
      interleukin-13 mediated eotaxin-3 gene up-regulation using HT-29 CL.19A cells
      expressing a dominant-negative signal transducer and activator of transcription
      6. Overall, these results demonstrate that epithelial eotaxin-3 is up-regulated
      in the context of a T helper 2 mediated inflammatory bowel disease via the signal
      transducer and activator of transcription 6, thus suggesting that the intestinal
      epithelium actively participates in the recruitment of eosinophils at the site of
      inflammation.

PMID- 16084753
TI  - Plant gamma-thionins: novel insights on the mechanism of action of a multi
      functional class of defense proteins.
AB  - This review focuses on the first plant defense protein class described in
      literature, with growth inhibition activity toward pathogens. These peptides were
      named gamma-thionins or defensins, which are small proteins that can be
      classified into four main subtypes according to their specific functions. Gamma
      thionins are small cationic peptides with different and special abilities. They
      are able to inhibit digestive enzymes or act against bacteria and/or fungi.
      Current research in this area focuses particularly these two last targets, being
      the natural crop plant defenses improved through the use of transgenic
      technology. Here, we will compare primary and tertiary structures of gamma
      thionins and also will analyze their similarities to scorpion toxins and insect
      defensins. This last comparison offers some hypothesis for gamma-thionins
      mechanisms of action against certain pathogens. This specific area has benefited
      from the recent determination of many gamma-thionin structures. Furthermore, we
      also summarize molecular interactions between plant gamma-thionins and fungi
      receptors, which include membrane proteins and lipids, shedding some light over
      pathogen resistance. Researches on gamma-thionins targets could help on plant
      genetic improvement for production of increased resistance toward pathogens.
      Thus, positive results recently obtained for transgenic plants and future
      prospects in the area are also approached. Finally, gamma-thionins activity has
      also been studied for future drug development, capable of inhibit tumor cell
      growth in human beings.

PMID- 16084754
TI  - Toxoplasma gondii: microneme protein MIC2.
AB  - The phylum Apicomplexa contains parasites responsible for a variety of diseases
      including malaria, cryptosporidiosis, and toxoplasmosis. One of the common
      features of these parasites is that they contain a set of apical organelles whose
      sequential secretion is required for the invasion of host cells. Microneme
      proteins are the main adhesins involved in the attachment to the host cell
      surface by apicomplexans. The microneme protein MIC2, produced by Toxoplasma
      gondii, is conserved in apicomplexans and serves as a model to understand the
      first steps of invasion by the phylum. New data about the structure-function
      relationship of MIC2 reinforce the critical role of this protein in the
      successful invasion of cells by Toxoplasma and reveal potential therapeutic
      targets that may be used to control toxoplasmosis.

PMID- 16084755
TI  - Oral malignancies following HSCT: graft versus host disease and other risk
      factors.
AB  - Allogenic hematopoietic stem cell transplantation (HSCT), a procedure that is
      widely used in the treatment of a large number of malignant and non-malignant
      hematological diseases, is still associated with a wide range of complications,
      one of the most important of which is graft versus host disease (GVHD). The
      patients undergoing allogenic HSCT are also at high risk of developing secondary
      neoplasms, particularly leukemias and lymphomas. Solid tumors are less frequent,
      and the incidence appears to increase over time; the most frequent solid tumors
      are squamous cell carcinomas. We found that almost all studies of solid cancers
      occurring after transplantation are based on relatively small numbers of cases
      which have been monitored for short periods, and little information is available
      on individual cancers. In particular, reports of oral cancers in HSCT are very
      few. Potential risk factors associated with the development of secondary solid
      cancers after HSCT have been well described. They include graft versus host
      disease (GVHD), preoperative regimens, with either radio-chemotherapy or
      chemotherapy alone, conditioning regimes, immunosuppressive GVHD prophylaxis,
      viral infection and chronic stimulation as a result of viral antigens, antigenic
      stimulation from histocompatibility differences between recipient and donor,
      primary diagnosis, interaction of any of these factors with genetic
      predisposition, and other factors such as sex and age. All patients treated with
      HSCT should therefore be closely followed over the long term with the aim of
      identifying the onset of secondary tumors as early as possible.

PMID- 16084756
TI  - Use of Comet assay to assess DNA damage in patients infected by Helicobacter
      pylori: comparisons between visual and image analyses.
AB  - Studies of DNA damage in gastric epithelial cells of Helicobacter pylori (H.
      pylori)-infected patients are conflicting, possibly due to different methods used
      for scoring DNA damage by Comet assay. Therefore, we compared the sensitivity of
      visual microscopic analysis (arbitrary units-scores and comets%) and image
      analysis system (tail moment), in the gastric epithelial cells from the antrum
      and corpus of 122 H. pylori-infected and 32 non-infected patients. The
      feasibility of cryopreserved peripheral blood lymphocytes and whole-blood cells
      for DNA damage biomonitoring was also investigated. In the antrum, the levels of
      DNA damage were significantly higher in H. pylori-infected patients with
      gastritis than in non-infected patients with normal mucosa, when evaluated by
      image analysis system, arbitrary units and comets%. In the corpus, the comets%
      was not sufficiently sensitive to detect the difference between H. pylori
      infected patients with gastritis and non-infected patients with normal mucosa.
      The image analysis system was sensitive enough to detect differences between non
      infected patients and H. pylori-infected patients with mild gastritis and between
      infected patients with moderate and severe gastritis, in both antrum and corpus,
      while arbitrary units and comets% were unable to detect these differences. In
      cryopreserved peripheral blood lymphocytes, the levels of DNA damage (tail
      moment) were significantly higher in H. pylori-infected patients with moderate
      and severe gastritis than in non-infected patients. Overall, our results indicate
      that the image analysis system is more sensitive and adequate to measure the
      levels of DNA damage in gastric epithelial cells than the other methods assayed.

PMID- 16084757
TI  - Learning outcomes in medical informatics: comparison of a WebCT course with
      ordinary web site learning material.
AB  - OBJECTIVE: The purpose of this study is to compare whether students' learning
      outcomes would be better in a designed learning environment (WebCT) than in a
      conventional web site (WWW) with similar course material but without special
      learning tools. CONTEXT: Third-year medical students in an introductory course on
      medical informatics at the University of Helsinki, Finland. METHODS: Students
      were randomly assigned to a WebCT group (n=39) and a WWW group (n=46). The
      students in the WebCT group utilized the course material in general discussion
      groups, special discussions about lectures, quizzes and students' own notes. The
      WWW group had access only to the course material. The learning outcome was
      assessed by administering an on-line examination and the learning experience of
      the students was assessed by an on-line quiz. RESULTS: The course grade was
      significantly higher in the WebCT group as compared to the WWW group. This
      finding was more prominent among females. The students of the WebCT group also
      experienced significantly more improvement in collaboration with the use of
      computers than the students in the WWW group. CONCLUSIONS: Based on our results,
      web-based learning seems to be more effective when students are provided with
      specially designed learning tools.

PMID- 16084758
TI  - Obese subjects with heart failure have lower N-terminal pro-brain natriuretic
      peptide plasma levels irrespective of aetiology.
AB  - N-terminal pro-brain natriuretic peptide (NT-proBNP) may be useful in the
      diagnosis of heart failure and ventricular dysfunction. Obesity is an independent
      cardiovascular risk factor. The purpose of this study was to measure NT-proBNP
      plasma levels in obese and non-obese subjects with heart failure and to compare
      levels in subjects with ischaemic and dilated aetiology. In this study, obese
      subjects had 63% lower NT-proBNP plasma levels than non-obese subjects (p <
      0.01). In multivariate analysis, BMI was inversely associated with NT-proBNP
      plasma levels (p < 0.05) and a 17% decrease in natriuretic peptide levels was
      attributed to obesity (p < 0.036). When we analyzed data according to the
      aetiology of heart failure, we found that both groups (ischaemic and dilated) had
      a 65% decrease in NT-proBNP plasma levels in obese subjects compared to non-obese
      subjects.

PMID- 16084759
TI  - The Modification of Diet in Renal Disease (MDRD) equations provide valid
      estimations of glomerular filtration rates in patients with advanced heart
      failure.
AB  - BACKGROUND: Glomerular filtration rate (GFR) has major prognostic implications in
      heart failure. Our objective was to validate the MDRD prediction equations for
      GFR in patients with advanced heart failure, and to compare their predictive
      performance to that of the Cockcroft-Gault (CG) equation. METHODS: We analysed
      GFR in 45 patients referred for heart transplantation evaluation. 51Cr-EDTA
      measured GFR was compared to GFR estimates obtained by MDRD1 and MDRD2 equations,
      CG equation using actual body weight, and ideal body weight. Regression analyses
      and Pearson correlations were performed, and Bland and Altman plots were drawn.
      ROC curves were obtained to illustrate each equation's ability to predict a GFR
      less than 60 ml/min/1.73 m2 (moderate renal impairment). RESULTS: Patients had a
      mean age of 52 years, and 69% were in NYHA class III. The mean EDTA-measured GFR
      was 46.9+/-17.2 ml/min/1.73 m2. The MDRD1 equation provided the best predictive
      model (narrowest limits of agreement; r = 0.766, p < 0.001), and the highest
      performance in predicting a GFR less than 60 ml/min/1.73 m2 (area under curve:
      0.901). CONCLUSIONS: MDRD equations, especially MDRD1, adequately predict GFR in
      advanced heart failure, with higher accuracy than the CG equation. MDRD1 also has
      higher performance in predicting a GFR less than 60 ml/min/1.73 m2.

PMID- 16084760
TI  - Progressive left ventricular hypertrophy after withdrawal of long-term ACE
      inhibition following experimental myocardial infarction.
AB  - BACKGROUND: Although discontinuation of chronic ACE inhibitor (ACEi) therapy
      after myocardial infarction (MI) is common in clinical practice, some clinical
      studies reported an increased incidence of ischemia-related events after
      withdrawal. To further address this issue, we assessed hemodynamic, neurohormonal
      and vascular consequences of withdrawing long-term ACEi treatment after
      experimental MI. METHODS: Rats were subjected to coronary ligation to induce MI,
      and received quinapril (15 mg/kg/day) from 2 weeks to 14 months post-MI.
      Subsequently, surviving rats were randomized to sacrifice at 0, 4, and 6 weeks
      after ACEi withdrawal. Rats were studied for signs of heart failure, hemodynamics
      and cardiac function, neurohormones, and vascular edothelial function. RESULTS:
      After discontinuation of ACEi treatment, plasma aldosterone levels increased
      between 0-4 weeks without further increment thereafter, suggesting persistent
      RAAS activation. Acetylcholine-induced aortic relaxation was impaired at 4 and 6
      weeks, indicating rapid and sustained development of endothelial vasodilator
      dysfunction after withdrawal. Moreover, 24% of the rats developed heart failure
      signs (edema, dyspnea), and 3 rats died, all within 4 weeks after withdrawal.
      Significantly increased N-ANP levels and lung weights at 4, but not at 6 weeks
      suggest a transient volume overload. Finally, LV/body weight ratios significantly
      increased between 0-4 as well as 4-6 weeks, indicating progressive LV
      hypertrophy. CONCLUSIONS: The observed alterations after withdrawing long-term
      post-MI quinapril treatment in the present study may account for an increased
      risk for ischemic events. Thus, our findings highlight the potentially harmful
      effects associated with abrupt discontinuation of long-term post-MI ACE
      inhibition, and imply careful clinical consideration in this matter.

PMID- 16084761
TI  - The relevance of comorbidities for heart failure treatment in primary care: A
      European survey.
AB  - AIM: To assess the impact of comorbidities on chronic heart failure (CHF)
      therapy. METHODS: The IMPROVEMENT-HF survey included 11,062 patients from 100
      primary care practices in 14 European countries. The influence of patient
      characteristics on drug regimes was assessed with multinomial logistical
      regression. RESULTS: Combined drug regimes were given to 48% of CHF patients,
      consisting of 2.2 drugs on average. Patient characteristics accounted for 35%,
      42% and 10% of the variance in one-, two- and three-drug regimes, respectively.
      Myocardial infarction (MI), atrial fibrillation (AF), diabetes, hypertension, and
      lung disease influenced prescribing most. AF made all combinations containing
      beta-blockers more likely. Thus for single drug regimes, MI increased the
      likelihood for non-recommended beta-blocker monotherapy (OR 1.3; 95% CI 1.2-1.4),
      while for combination therapy recommended regimes were most likely. For both
      hypertension and diabetes, ACE-inhibitors were the most likely single drug, while
      the most likely second drugs were beta-blockers in hypertension and digoxin in
      diabetes. CONCLUSIONS: Patient characteristics have a clear impact on prescribing
      in European primary care. Up to 56% of drug regimes were rational taking patient
      characteristics into account. Situations of insufficient prescribing, such as
      patients post MI, need to be addressed specifically.

PMID- 16084762
TI  - Short-term effects of levosimendan and prostaglandin E1 on hemodynamic parameters
      and B-type natriuretic peptide levels in patients with decompensated chronic
      heart failure.
AB  - BACKGROUND: Both levosimendan and prostaglandin E1 (PGE1) have beneficial effects
      on hemodynamic parameters and outcome compared to dobutamine in decompensated
      chronic heart failure (CHF). AIMS: We compared short-term effects of levosimendan
      versus PGE1 on hemodynamic parameters and B-type natriuretic peptide levels (BNP)
      in patients with decompensated CHF. METHODS AND RESULTS: 73 patients (cardiac
      index < 2.5 L/min/m2, pulmonary capillary wedge pressure (PCP) >15 mmHg) with
      decompensated CHF were randomised to treatment with either a 24 h-infusion of
      levosimendan (n=38) or a chronic infusion of PGE1 (n = 35). Hemodynamic
      parameters and BNP were measured at baseline, 24 and 48 h, BNP levels were also
      measured after 1 week. Baseline characteristics including concomitant medication
      were similar in both groups. Levosimendan and PGE1 increased cardiac output (CO)
      after 24 and 48 h. Levosimendan increased CO twice as much as PGE1 (24 h:
      Levosimendan +1.1 +/- 0.1 L/min, PGE1 +0.6 +/- 0.1 L/min, p < 0.001). Both drugs
      produced a comparable reduction in PCP and pulmonary artery pressure after 24 and
      48 h. Levosimendan decreased BNP by 28% after 24 h and 22% after 48 h, but
      effects disappeared after 1 week. In contrast, PGE1 decreased BNP by 15% after 48
      h (no change at 24 h), but a decrease of 20% was sustained at 1 week.
      CONCLUSIONS: The differential beneficial effects of levosimendan (greater
      increase in CO) and PGE1 (sustained decrease in BNP) may have a potential impact
      on clinical outcome.

PMID- 16084763
TI  - Antidepressant medication use and restless legs syndrome in patients presenting
      with insomnia.
AB  - BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is a movement disorder that
      frequently results in significant complaints of insomnia. Based on published case
      reports, it is commonly believed that RLS can be caused or exacerbated by
      antidepressant agents, thus complicating the treatment of depressed patients who
      are already prone to sleep disturbances. However, there are no systematic studies
      demonstrating an association between the clinical diagnosis of RLS and the use of
      antidepressant medication. PATIENTS AND METHODS: Retrospective chart review of
      200 consecutive patients presenting for evaluation of sleep initiation insomnia
      at an accredited freestanding sleep disorders center that is part of an
      integrated health care system. RESULTS: Mean age (+/-SD) of patients was 51.1+/
      14.8 years; 60% were women. Fifty-six percent carried a diagnosis of depression,
      38% were being treated with antidepressant medication at presentation and 45% met
      clinical diagnostic criteria for RLS. There were no statistical associations,
      either by chi(2) analysis or odds ratios, between RLS and antidepressant use or
      use of any specific class of antidepressant. Positive associations with RLS were
      found for patients receiving treatment for hypothyroidism and those taking
      estrogens; a significant negative association was found for patients receiving
      beta adrenergic antagonists. CONCLUSIONS: Although there are anecdotal reports of
      antidepressant use causing or exacerbating RLS, systematic study of this issue
      fails to corroborate an association.

PMID- 16084764
TI  - Hypersomnolence and increased REM sleep with low cerebrospinal fluid hypocretin
      level in a patient after removal of craniopharyngioma.
AB  - Here we report a hypersomnolent girl with extensive hypothalamic damage after
      removal of a craniopharyngioma. The presence of a short sleep latency, sleep
      onset REM periods during a multiple sleep latency test (MSLT) and negative HLA
      DQB1*0602 typing suggested a diagnosis of symptomatic narcolepsy. Low
      cerebrospinal fluid hypocretin-1 level indicated destruction of hypocretin
      producing neurons in the hypothalamus. An increased amount of REM sleep and a
      lack of REM sleep cyclicity documented by all-night polysomnography were
      different findings from previous reports of hypocretin-deficient idiopathic
      symptomatic narcolepsy. A more global hypothalamic lesion demonstrated by brain
      magnetic resonance imaging (MRI) after surgery seemed to cause marked
      disinhibition of REM sleep as well as hypersomnolence in this patient.

PMID- 16084765
TI  - Daytime sleepiness is not increased in mild to moderate multiple sclerosis: a
      pupillographic study.
AB  - BACKGROUND: Daytime sleepiness has been described in multiple sclerosis (MS); a
      combination of MS and narcolepsy has also been observed in a few case reports. In
      this study, we investigated daytime sleepiness in a general sample of MS patients
      compared to healthy controls with the pupillographic sleepiness test (PST) and
      the Epworth and Stanford sleepiness scales (ESS, SSS). METHODS: A PST was
      performed in consecutive MS patients and controls. Additionally, a questionnaire
      including the ESS and the SSS was applied. RESULTS: Sixty-one MS patients (29 men
      and 32 women, age 34.5+/-8.3 years, mean disease duration 7.4+/-6.6 years,
      expanded disability status scale (EDSS) 1.7+/-1.2 (mean +/- sd)) and 42 age
      matched controls (13 men and 29 women, age 36.9+/-12.9 years) participated in
      this study. In the MS group, the pupillary unrest index (PUI) was 5.0+/-2.0, the
      ESS 7.4+/-3.5 and the SSS 2.4+/-1.2, whereas in the control group, the PUI was
      4.7+/-1.8, the ESS 8.4+/-4.0 and the SSS 2.4+/-1.2 (mean +/- sd). These
      differences were not significant. No correlation was found between PUI and the
      ESS or the SSS. Furthermore, no correlation was found between EDSS and sleepiness
      measured by PUI, ESS and SSS. CONCLUSION: In a general sample of MS patients with
      mild to moderate disease, there was no evidence for overall increased daytime
      sleepiness compared to healthy controls.

PMID- 16084766
TI  - Current challenges in antimicrobial chemotherapy: the impact of extended-spectrum
      beta-lactamases and metallo-beta-lactamases on the treatment of resistant Gram
      negative pathogens.
AB  - Gram-negative bacteria that produce extended-spectrum- and metallo-beta
      lactamases are being discovered at an alarming rate, while the development of new
      antimicrobial agents has almost ground to a standstill. A body of experience
      exists with the detection and treatment of extended-spectrum beta-lactamase
      producing organisms (Klebsiella pneumoniae and Escherichia coli), suggesting that
      knowledge of their existence and dissemination might have an impact on
      therapeutic choices and patient outcomes via targeted empirical antimicrobial
      selection and infection control practices. It is unclear whether the same mandate
      exists for the detection of metallo-beta-lactamases. As dictated by local
      susceptibility patterns, in many settings worldwide empirical therapy in serious
      nosocomial infections now requires the use of carbapenems alone or in combination
      with a second antibiotic that is also effective against Gram-negative pathogens;
      colistin is advocated as the empirical drug of choice in the setting of multidrug
      resistant Pseudomonas aeruginosa infections, although high doses of beta-lactams
      might prove to be effective.

PMID- 16084767
TI  - Microdialysis for in vivo pharmacokinetic/pharmacodynamic characterization of
      anti-infective drugs.
AB  - Inadequate tissue penetration of antibiotics can lead to therapeutic failure and
      bacterial resistance. Pharmacokinetic evaluation of antibiotics should therefore
      be based on tissue rather than serum concentrations. Over several years, tissue
      concentration data obtained by methods such as tissue biopsies have flawed the
      correct interpretation of antibiotic tissue distribution. Microdialysis--a semi
      invasive catheter-based sampling technique--has been employed for the in vivo
      measurement of antibiotic tissue pharmacokinetics. Owing to selective access to
      the target site for most anti-infective drugs, microdialysis satisfies regulatory
      requirements for pharmacokinetic distribution studies and might become a
      reference technique for tissue distribution studies in the near future.
      Furthermore, microdialysis might contribute to the definition of meaningful
      surrogate markers for antibiotic efficiency during drug development.

PMID- 16084768
TI  - Predicting the future Streptococcus pneumoniae resistance landscape.
AB  - Streptococcus pneumoniae resistance to antibiotics is considered a public health
      problem, and yet the link between year-to-year increases in resistance and
      antimicrobial consumption has been difficult to prove. Mathematical models and
      epidemiological studies have shown that there is no linear relationship between
      consumption and resistance, and that increasing resistance is caused by the
      removal of susceptible strains from the population. Pneumococcal conjugate
      vaccine has also been shown to have an impact over resistance. A model that
      relates resistance with the cumulative consumption of antibiotics over time
      explains low resistance rates in countries such as Germany and plateaus in
      resistance in the US. Moreover, understanding this temporal relationship allows
      us to predict that if the cumulative consumption stabilizes so will the
      resistance rates.

PMID- 16084769
TI  - Prospects and challenges of developing new agents for tough Gram-negatives.
AB  - Historically, the medical profession has been successful in treating most
      bacterial infections in humans with synthetic second- and third-generation
      antibiotics. Recently, the prospects for continued success have dimmed with the
      increase in multidrug-resistant stains of bacteria. Infections caused by the Gram
      negative bacteria Pseudomonas aeruginosa and Acinetobacter spp. in particular
      have increased in frequency and severity, and become progressively more difficult
      to treat. Contributors to disease severity include chronic infections due to
      mutator strains, persister cells and biofilms. The worst-case scenario of
      infections susceptible only to toxic polymixins is now a reality. The need to
      address the treatment of multidrug-resistant pathogens with innovative
      combination approaches and/or novel antibacterial agents is occurring in the
      context of reduced investment in antimicrobial drug discovery by the
      pharmaceutical industry.

PMID- 16084770
TI  - Current drug development portfolio for antimalarial therapies.
AB  - In response to the emergence of parasite drug resistance to currently deployed
      antimalarials, the scientific community, in partnership with the pharmaceutical
      industry and public organizations, has fashioned an antimalarial drug development
      portfolio for the sustained development and registration of safe, effective and
      cheap antimalarial medicines. The management of this portfolio is being driven by
      MMV (Medicines for Malaria Venture), with a number of projects recently reaching
      the clinical end of this drug development pipeline.

PMID- 16084771
TI  - Awakening gene therapy with Sleeping Beauty transposons.
AB  - Sleeping Beauty transposons have the potential for use as chromosome-integrating
      vectors for non-viral gene therapy. Recent preclinical data from mouse models for
      human genetic disorders have shown efficacy for the Sleeping Beauty transposon
      system in the treatment of hemophilia, tyrosinemia type I, junctional
      epidermolysis bullosa and type 1 diabetes. Methods have also been developed to
      deliver Sleeping Beauty transposons to the lung, liver and tumors for treatments
      for cystic fibrosis, cardiovascular and metabolic diseases, and cancer. Recent
      studies characterizing site selection for integration and insertional mutagenesis
      indicate that the Sleeping Beauty transposon system may be a safer alternative
      than viral approaches for gene therapy.

PMID- 16084772
TI  - Research strategies for the treatment of biothreats.
AB  - Whether it is a layperson in the street or a politician in the Senate, there is
      widespread fear over the consequences of biothreats. In response to these fears,
      a wide range of treatments has been developed. These include antibiotics
      (conventional and unconventional uses), nucleic acids (analogues, antisense,
      ribozymes and DNAzymes), immunomodulators, antibodies, bacteriophage therapy and
      micro-encapsulation. Furthermore, there are often additional benefits when these
      therapeutics are used in combination, rather than alone. Although there has been
      much investment in therapeutics against a terrorist threat for reasons of
      national security, there are likely to be far greater benefits and applications
      on domestic and world health.

PMID- 16084773
TI  - FcgammaRIIa is a target for modulation by TNFalpha in human neutrophils.
AB  - Activation of neutrophils by the interaction of immune complexes with Fc gamma
      receptors (FcgammaR) is amplified in tumor necrosis factor-alpha (TNFalpha)
      primed cells, whereas interleukin-10 (IL-10) has been reported to suppress
      cytokine-mediated neutrophil activation. We examined whether the expression and
      function of FcgammaR in human neutrophils is modulated by TNFalpha and IL-10 in
      vitro, and whether FcgammaRIIa expression is altered following treatment with the
      TNFalpha inhibitor infliximab in rheumatoid arthritis (RA) patients in vivo.
      TNFalpha treatment induced upregulation of expression and function of the major
      activating Fc receptor, FcgammaRIIa, in neutrophils from healthy donors.
      Unexpectedly, treatment with IL-10 led to gain of FcgammaRIIa function in
      TNFalpha-primed neutrophils. In neutrophils from RA patients initiating
      infliximab therapy and followed longitudinally through consecutive treatments,
      FcgammaRIIa protein decreased during the course of TNFalpha blockade, indicating
      that FcgammaRIIa is a target of TNFalpha modulation in human neutrophils in vivo.

PMID- 16084774
TI  - A cellular screening assay to test the ability of PKR to induce cell death in
      mammalian cells.
AB  - Long double-stranded RNA (>30 bp), usually expressed in cells infected with RNA
      viruses, triggers antiviral responses that induce apoptosis of the infected
      cells. PKR can be selectively activated in glioblastoma cells by in situ
      generation of dsRNA following introduction of antisense RNA complementary to an
      RNA expressed specifically in these cells. Harnessing PKR for the selective
      killing of cancer cells is potentially a powerful strategy for treating cancer,
      but we were unable to induce apoptosis by this approach in a T cell lymphoma. We
      therefore established a cellular screening assay to test the ability of PKR to
      induce death in cell lines, especially those originating from human cancers. This
      "PKR killing screen" is based on the infection of cells with an adenoviral vector
      encoding GyrB-PKR, followed by coumermycin treatment. Cancers represented by cell
      lines in which PKR activation leads to cell death are good candidates for the
      dsRNA killing approach, using antisense to RNA molecules specifically expressed
      in these cells. The PKR killing screen may also serve as a tool for exploring PKR
      signaling and other related pathways, by identifying new cases in which PKR
      signaling is inhibited or impaired.

PMID- 16084775
TI  - Male germ-line cells are at risk following direct-injection retroviral-mediated
      gene transfer in utero.
AB  - The recent observation of vector sequences in the semen of men undergoing
      clinical gene therapy for hemophilia has highlighted the need to evaluate the
      risk of inadvertent germ-line transduction in a clinically relevant animal model.
      In the present study, we used three different approaches to investigate whether
      the germ line is at risk of inadvertent alteration following in utero retroviral
      gene transfer in the clinically relevant, random-bred sheep model. First, we
      conducted breeding studies. All organs from the 10 resultant offspring were
      devoid of proviral DNA, suggesting that the germ line had not been altered. As a
      second approach, we performed PCR on gradient-enriched, forensically purified
      sperm cells from in utero-transduced rams. The purified sperm cells from 6 of 19
      of these rams were PCR positive for provirus, providing compelling evidence that
      the germ line had been transduced. As a third approach, we performed
      immunohistochemistry on sections of the testis from in utero-transduced sheep.
      Numerous somatic cells and very low levels of germ cells within the male
      reproductive tissues were transduced. In conclusion, our analysis on over 3 x
      10(9) sperm cells suggests that the direct-injection approach employed in these
      studies may result in the inadvertent transduction of very low numbers of male
      germ cells.

PMID- 16084776
TI  - Design and baseline characteristics of the osteoporotic fractures in men (MrOS)
      study--a large observational study of the determinants of fracture in older men.
AB  - Very little information is available to direct the prevention or management of
      osteoporosis in men. The Osteoporotic Fractures in Men (MrOS) Study is a
      prospective cohort study designed to examine the extent to which fracture risk is
      related to bone mass, bone geometry, lifestyle, anthropometric and neuromuscular
      measures, and fall propensity, as well as to determine how fractures affect
      quality of life in men. The study is also designed to understand how osteoporosis
      is related to prostate disease. At baseline, participants completed
      questionnaires regarding medical history, medications, physical activity, diet,
      alcohol intake, and cigarette smoking. Objective measures of anthropometric,
      neuromuscular, vision, strength, and cognitive variables were obtained. Skeletal
      assessments included DEXA, calcaneal ultrasound, and vertebral radiographs.
      Vertebral and proximal femoral QCT was performed on a subset (65%). Serum, urine,
      and DNA specimens were collected. After the baseline assessments, a questionnaire
      is mailed to participants every 4 months to ascertain incident falls, fractures,
      prostate cancer, and deaths. After an average of 4.5 years, participants are
      scheduled to return for a second comprehensive visit. Men were eligible if > or
      =65 years. 5995 men enrolled with a mean (+/-SD) age of 73.7 (+/-5.9) years, 11%
      of which were minorities. Most rated their health as good/excellent. Few were
      current smokers, although 59% had smoked previously, and 35% reported no alcohol
      intake, while 47% consumed at least 2 drinks per week. The mean (range) body mass
      index was 26.9 kg/m2 (17-56). A non-traumatic fracture after age 50 was reported
      by 17% of the cohort. The MrOS cohort should provide valuable information
      concerning the determinants of fracture in men and should help set the stage for
      the development of effective methods to identify those at risk.

PMID- 16084777
TI  - Medical cost analysis: application to colorectal cancer data from the SEER
      Medicare database.
AB  - Incompleteness is a key feature of most survival data. Numerous well established
      statistical methodologies and algorithms exist for analyzing life or failure time
      data. However, induced censorship invalidates the use of those standard analytic
      tools for some survival-type data such as medical costs. In this paper, some
      valid methods currently available for analyzing censored medical cost data are
      reviewed. Some cautionary findings under different assumptions are envisioned
      through application to medical costs from colorectal cancer patients. Cost
      analysis should be suitably planned and carefully interpreted under various
      meaningful scenarios even with judiciously selected statistical methods. This
      approach would be greatly helpful to policy makers who seek to prioritize health
      care expenditures and to assess the elements of resource use.

PMID- 16084778
TI  - Age-related neuropathology, cognitive decline, and Alzheimer's disease.
AB  - In the last 20 years, there have been tremendous strides made in the
      understanding of the molecular and cellular processes that occur during brain
      aging, as well as our understanding of age-related disorders of the central
      nervous system (CNS). Aging is associated with a decline in cognitive
      performance, and is the biggest risk factor for the development of Alzheimer's
      disease (AD), although the underlying basis for both of these observations is
      poorly defined. Both normal aging and AD are associated with overlapping and
      increased levels of pathology. Numerous reports have now linked elevations in
      pathology as potential mediators of cognitive decline in the elderly, with most
      studies focusing on the role of AD-related pathology. However, it is important to
      point out that there are numerous other pathological features observed in the
      aging brain including corpora amylacea, argyrophilic grains, neuromelanin, and
      lipofuscin. In this review, I discuss the decreased cognitive performance
      observed during normal aging, the potential for pathology to alter neuronal
      function and neuronal viability during normal brain aging, and the potential for
      common pathologies to either inhibit or promote the development of age-related
      disorders such as AD.

PMID- 16084779
TI  - FT-IR approaches on amyloid fibril structure.
AB  - This review treats recent achievements of Fourier-transform infrared absorption
      spectroscopy on protein science, especially on amyloid fibril structure. It
      includes the brief explanation of theoretical background, description of related
      techniques, and recent applications to analysis of fibril structure. Concerns to
      theoretical background, successful analysis of Amide I in terms of transition
      dipole coupling between the C=O oscillators in peptide main chain has been
      described. The theory enables us to estimate a content of secondary structure in
      a protein. Related experimental techniques such as linear dichroism measurement,
      application of microscope, and isotope labeling, are introduced. The linear
      dichroism measurement brings direct information on molecular orientation,
      microscope enables to treat a well-prepared particle, and isotope-label technique
      allows our structural discussion with one-residue resolution. Application of IR
      absorption spectroscopy and related techniques on amyloid fibril structure is
      reviewed. The model obtained is compared with protein native structure.

PMID- 16084780
TI  - The three-dimensional structure of beta2 microglobulin: results from X-ray
      crystallography.
AB  - beta2-microglobulin, the light chain component of the major histocompatibility
      complex I, is involved in the development of DRA, an amyloid deposition disease
      occurring in man. Specifically, the beta2-microglobulin component, dissociated
      form the complex heavy chain, gives rise to amyloidogenic deposits in the joints
      of patients exposed to long dialysis periods. beta2-microglobulin three
      dimensional structure is based on an antiparallel beta-barrel fold, with
      immunoglobulin domain topology, displaying structural flexibility in the crystal
      and NMR structures so fare determined. The structural bases of amyloidogenic
      potential in beta2-microglobulin can be related to local unfolding, to the
      tendency to aggregate laterally through non-compensated beta-strands, and partly
      also to its trend towards N-terminal proteolytic degradation. Such trends emerge
      quite clearly from inspection of a limited number of crystal structures of beta2
      microglobulin as an isolated chain, separated form the major histocompatibility
      complex I heavy chain.

PMID- 16084781
TI  - Kinetic analysis of the polymerization and depolymerization of beta(2)
      microglobulin-related amyloid fibrils in vitro.
AB  - beta(2)-Microglobulin-related (Abeta(2)M) amyloidosis is a serious complication
      in patients on long-term dialysis, and partial unfolding of beta(2)-microglobulin
      (beta(2)-m) is believed to be prerequisite to its assembly into Abeta(2)M amyloid
      fibrils. Many kinds of amyloid-associated molecules (e.g., apolipoprotein E
      (apoE), glycosaminoglycans (GAGs), proteoglycans (PGs)) may contribute to the
      development of Abeta(2)M amyloidosis. The formation of Abeta(2)M amyloid fibrils
      in vitro was first observed at low pH (2.0-3.0). Very recently, low
      concentrations of 2,2,2-trifluoroethanol (TFE) and the sub-micellar concentration
      of sodium dodecyl sulfate, a model for anionic phospholipids, have been reported
      to cause the extension of Abeta(2)M amyloid fibrils at a neutral pH, inducing
      partial unfolding of beta(2)-m and stabilization of the fibrils. Moreover, apoE,
      GAGs and PGs were found to stabilize Abeta(2)M amyloid fibrils at a neutral pH,
      forming a stable complex with the fibrils. Some GAGs, especially heparin enhanced
      the fibril extension in the presence of TFE at a neutral pH. Some PGs, especially
      biglycan also induced the polymerization of acid-denatured beta(2)-m. These
      findings are consistent with the hypothesis that in vivo, specific molecules that
      affect the conformation and stability of beta(2)-m and amyloid fibrils will have
      significant effects on the deposition of Abeta(2)M amyloid fibrils.

PMID- 16084782
TI  - San Francisco pedestrian injury surveillance: mapping, under-reporting, and
      injury severity in police and hospital records.
AB  - GOALS: Police reports of severely injured pedestrians help identify hazardous
      traffic areas in San Francisco, but they under-report non-fatal collisions. We
      set out to: identify injured pedestrians who were missing from police collision
      reports, see what biases exist in injury reporting and assess the utility of
      broad categories of police severe injury (including fatal) for mapping and
      analysis. METHODS: We linked data on injured pedestrians from police collision
      reports listed in the Statewide Integrated Traffic Reporting System (SWITRS, n =
      1991) with records of pedestrians treated at San Francisco General Hospital
      (SFGH, n = 1323) for 2000 and 2001. Data were analyzed using bivariate
      statistics, logistic regression and mapping. RESULTS: : We found that police
      collision reports underestimated the number of injured pedestrians by 21%
      (531/2442). Pedestrians treated at SFGH who were African-American were less
      likely then whites (odds ratio = 0.55, p-value < or= 0.01), and females were more
      likely than males (odds ratio = 1.5, p-value < or = 0.01) to have a police
      collision report. Over 70% of pedestrians deemed by the police to have a severe
      injury received treatment at SFGH, regardless of the collision's distance from
      SFGH. The sensitivity of a police-designated severe injury (including fatal) was
      69% and the specificity was 89% when compared with a known SFGH assessment. But,
      sensitivity declined when we included pedestrians without a SFGH record.
      CONCLUSION: Though collision reports have demonstrated limitations, broad
      categories of police severity may be sensitive enough to map locations where
      numerous severe injuries occur, for timely countermeasure selection.

PMID- 16084783
TI  - Application of the extended RSA models in studies of particle deposition at
      partially covered surfaces.
AB  - This paper reviews the application of the extended random sequential adsorption
      (RSA) approaches to the modeling of colloid-particle deposition (irreversible
      adsorption) on surfaces precovered with smaller particles. Hard (noninteracting)
      particle systems are discussed first. We report on the numerical simulations we
      performed to determine the available surface function, jamming coverage, and pair
      correlation function of the larger particles. We demonstrate the effect of the
      particle size ratio and the small particle surface coverage. We found that the
      numerical results were in reasonable agreement with the formula stemming from the
      scaled-particle theory in 2D with a modification for the sphere geometry. Next,
      we discuss three approximate models of adsorption allowing electrostatic
      interaction of colloid particles at a charged interface, employing a many-body
      superposition approximation. We describe two approaches of the effective hard
      particle approximation next. We demonstrate the application of the effective hard
      particle concept to the bimodal systems and present the effect of electrolyte
      concentration on the effective particle size ratio. We present the numerical
      results obtained from the theoretical models of soft-particle adsorption at
      precovered surfaces. We used the effective hard-particle approximation to
      determine the corresponding simpler systems of particles, namely the system of
      hard spheres and the system of hard discs at equilibrium. We performed numerical
      computations to determine the effective minimum particle surface-to-surface
      distance, available surface function, jamming coverage, and pair-correlation
      function of the larger particles at various electrolyte ionic strengths and
      particle size ratios. The numerical results obtained in the low-surface coverage
      limit were in good agreement with the formula stemming from the scaled-particle
      theory with a modification for the sphere geometry and electrostatic interaction.
      We compared the results of numerical computations of the effective minimum
      particle surface-to-surface distance obtained using the 2D, 3D, and curvilinear
      trajectory model. The results obtained with the 3D and curvilinear trajectory
      models indicate that large-particle/substrate attractive interaction
      significantly reduces the kinetic barrier to large, charged-particle adsorption
      at a surface precovered with small, like-charged particles. The available surface
      function and jamming-coverage values predicted using the simplified 3D and the
      more sophisticated curvilinear trajectory models are similar, while the results
      obtained with the 2D model differ significantly. The pair-correlation function
      suggests different structures of monolayers obtained with the three models.
      Unlike the three models of the electrostatic interaction, both effective hard
      particle approximations give almost identical results. Results of this research
      clearly suggest that the extended RSA approaches can fruitfully be exploited for
      numerical simulations of colloid-particle adsorption at precovered surfaces,
      allowing the investigation of both hard and soft-particle systems.

PMID- 16084784
TI  - Fixed dilated pupil after penetrating keratoplasty for macular corneal dystrophy
      and keratoconus.
AB  - PURPOSE: To identify predisposed eyes, risk factors, and protective measures and
      to evaluate methods of treatment for fixed dilated pupil after penetrating
      keratoplasty (PKP) for macular corneal dystrophy (MCD) and keratoconus. DESIGN:
      Retrospective observational case series. METHODS: A retrospective review was
      conducted of the charts of 195 patients who had PKP for MCD and of 1800 patients
      who had PKP for keratoconus at the King Khaled Eye Specialist Hospital in Riyadh,
      Saudi Arabia. The review included an evaluation of the preoperative and
      intraoperative data and the postoperative course. In addition, clinical
      examinations at the last visit and photographs of the cornea, pupil, iris, and
      lens were analyzed. RESULTS: Twenty-one eyes of 18 patients had fixed dilated
      pupil after PKP; 15 eyes of 12 patients had MCD, and six eyes of six patients had
      keratoconus. A rise in intraocular pressure (IOP) during the procedure was seen
      in five patients (23.8%). Fixed dilated pupil was documented on the first and
      second postoperative days and the second postoperative week in 17 (80.9%), one
      (4.8%), and three (14.3%) eyes, respectively. Six eyes (28.6%) of six patients
      had severe eye inflammation. Only one eye (4.8%) regained partial reactivity of
      the pupil on follow-up visits. Seven eyes (33.3%) experienced lens changes; nine
      eyes (42.8%) had elevated IOP on the first postoperative day, and none of the
      eyes had chronic glaucoma. CONCLUSION: Inflammatory and multifactorial pathologic
      condition can cause fixed pupil after PKP. Atropine use, keratoconus, and high
      IOP are not constant findings in this syndrome. Awareness of the risk factors of
      fixed dilated pupil will help prevent against its occurrence.

PMID- 16084785
TI  - Genome-wide scan for myopia in the Old Order Amish.
AB  - PURPOSE: To identify myopia susceptibility genes influencing common myopia in 34
      Old Order Amish families, a genetically well-defined founder population. DESIGN:
      A prospective study of families with myopia consisting of a minimum of two
      individuals affected with myopia. METHODS: Extended families consisting of at
      least two siblings affected with myopia were ascertained. A genome-wide linkage
      scan using 387 markers was conducted by the Center for Inherited Disease Research
      (CIDR). Linkage analyses were conducted with parametric (autosomal dominant,
      fixed penetrance model) and nonparametric methods. Model-free linkage analysis
      was also performed maximizing over penetrance and over dominance (that is,
      fitting a wide range of both dominant and recessive models). RESULTS: Under the
      fixed penetrance model, the maximum two-point heterogeneity LOD score (HLOD) was
      1.59 at D20S451 and the maximum multipoint HLOD was 1.92 at D6S1021. The
      nonparametric maximum multipoint (NPL) at D3S2427 had a P-value of .0005. Under
      the model-free analysis, multipoint heterogeneity LOD scores of 2.03 were
      observed on both chromosomes 8 (under a recessive model between D8S1130 and
      D8S1106) and X (under a recessive model between DXS6800 and DXS6789). Reanalyses
      of chromosomes 3, 6, 8, 20, and X using the best penetrance models resulted in
      maximum multipoint HLODs of 1.84 at D3S3053; 1.84 at D3S2427; 2.04 at D8S1130;
      and 2.34 at DXS6800. CONCLUSIONS: The locus on chromosome 8p23 independently
      confirms a report by Hammond and associates mapping a myopia quantitative trait
      loci (QTL) to this region.

PMID- 16084786
TI  - Primary viscocanalostomy for juvenile open-angle glaucoma.
AB  - PURPOSE: To evaluate the efficacy and safety of primary viscocanalostomy for
      medically uncontrolled juvenile open-angle glaucoma (JOAG). DESIGN: Prospective,
      noncomparative, interventional case-series study. METHODS: The study included 20
      eyes of 20 consecutive patients with medically uncontrolled JOAG who were treated
      by viscocanalostomy at one institution. No surgical or laser procedure preceded
      viscocanalostomy. Surgical outcome was defined as an overall success by the
      following criteria: no visual field deterioration, no optic-neuropathy
      progression, postoperative intraocular pressure IOP < or =20 mm Hg, and IOP
      reduction > or =30% compared with baseline values with or without medication.
      When medications were not required, success was defined as complete. Cases that
      did not fulfill the aforementioned criteria and cases in which a surgical
      revision or further goniopuncture was performed were defined as a failure.
      RESULTS: Gender distribution was similar. Fourteen eyes belonged to the white
      race; five eyes belonged to the black race, and one eye belonged to Arab
      ethnicity. Mean age (+/-SD) at operation was 33.77 +/- 6.16 years, with the mean
      preoperative IOP (+/-SD) at 22.9 +/- 4.77 mm Hg. Thirty-six months after
      operation, 16 cases (80%) were considered an overall success. In 11 cases (55%),
      success was complete. Four cases (20%) were considered failures. No serious
      complications were documented either during or after operation. In two cases
      (10%), we documented a spontaneously reabsorbed microhyphema. Trabeculo-Descemet
      membrane microperforation occurred in two cases (10%). In two other cases (10%),
      Trabeculo-Descemet-membrane perforation occurred and was accompanied by iris
      prolapse that needed peripheral iridectomy. CONCLUSION: Primary viscocanalostomy
      can efficiently and safely reduce intraocular pressure in cases of medically
      uncontrolled JOAG and provide a rational alternative to conventional surgical
      modalities.

PMID- 16084787
TI  - Effect of full tendon transposition augmented with posterior intermuscular suture
      for paralytic strabismus.
AB  - PURPOSE: To evaluate the results of the full rectus muscle transposition
      augmented with a posterior intermuscular suture for paralytic strabismus. DESIGN:
      Single-center, retrospective, interventional case series. METHODS: This study
      retrospectively reviewed the medical records from November 1994 to September 2004
      of 16 patients who underwent the full tendon transposition that was augmented
      with posterior intermuscular suture for paralytic strabismus. This series
      evaluated the results of a single transposition surgery; five patients had
      previous nontransposition strabismus surgery. The following data were analyzed
      before and after the operation: (1) the angle of deviation in the primary
      position, (2) the presence of diplopia in the primary position, (3) the binocular
      single visual fields, (4) the presence of an abnormal head posture, (5) the
      motility of the affected eye, and (6) the procedure that was performed. RESULTS:
      The preoperative angle of deviation in the primary position was 59 +/- 22 prism
      diopter (prism diopter; range, 30 to 115 prism diopter) compared with 17 +/- 12
      prism diopter (range, -10 to 40 prism diopter) after the operation. The
      preoperative binocular single visual fields improved from 0 degrees to 60 +/- 25
      degrees (range, 0 to 90 degrees) after the operation. Diplopia in the primary
      position was resolved in 11 patients (69%) after the operation. There were no
      complications such as scleral perforation, unwanted vertical deviations, or
      anterior segment ischemia in any of the cases during the procedure and
      postoperative follow-up. CONCLUSION: Full tendon transposition that is augmented
      with a posterior intermuscular suture is an effective procedure that results in
      improved ocular alignment in patients with paralytic strabismus and has a
      favorable complication profile.

PMID- 16084788
TI  - Vitronectin: a possible determinant of adenovirus type 19 tropism for human
      corneal epithelium.
AB  - PURPOSE: Adenoviruses typically demonstrate specific tissue tropisms, as in the
      association of Ad19 with epidemic keratoconjunctivitis. We sought to determine
      factors that might influence the apparent tropism of Ad19 for the cornea. DESIGN:
      Laboratory investigation. METHODS: Adenovirus serotypes Ad2, 5, 9, 10, 11, 13,
      and 19 were compared for their capacity to replicate in human corneal epithelial
      cells (HCECs) in culture. Organotypically cultured human corneas were infected
      with Ad19 or Ad2, and viral titers were compared after 7 days. Replication of
      both viruses was compared in HCECs cultured on various extracellular matrices.
      Western blot analysis and immunohistochemistry were applied to human donor
      corneas and HCECs. RESULTS: One week after infection of HCEC monolayer cultures,
      Ad2 titers were significantly higher than any of the other viruses tested (P
      <.05). In organotypic corneal cultures, Ad19 titers were significantly higher
      than Ad2 (P = .0003). Ad2 replication in HCECs equaled or exceeded that of Ad19
      on all extracellular matrices except vitronectin, where Ad2 replication was
      reduced and Ad19 replication enhanced (P <.0001). Vitronectin was detected by
      immunohistochemistry within the corneal epithelial basement membranes of human
      donor corneas. Increased alpha(v) integrin expression and greater tyrosine kinase
      phosphorylation in HCECs cultured on vitronectin were demonstrated by Western
      blot analysis. CONCLUSIONS: In vitro, vitronectin enhances growth of Ad19,
      possibly by up-regulation of receptor alpha(v) integrins and increased activity
      of tyrosine kinases necessary for adenoviral internalization. We hypothesize that
      differential tissue tropisms for adenoviruses may derive in part from tissue
      specific extracellular matrix expression.

PMID- 16084789
TI  - The use of Surgi Wrap in delayed adjustable strabismus surgery.
AB  - PURPOSE: To determine the effect of Surgi Wrap (MacroPore Biosurgery, Inc, San
      Diego, California, USA) in delayed adjustable strabismus surgery. DESIGN: An
      animal study. METHODS: A prospective, masked-observer, controlled study was
      performed in rabbits. Forty-eight eyes of 24 rabbits were divided into two
      groups. After recession of the superior rectus muscle (SRM), Surgi Wrap was
      applied beneath and over the SRM in the Surgi Wrap group, and no barrier was
      applied in the control group. Delayed adjustment was performed once on each
      superior rectus muscle at 1, 2, and 3 weeks after surgery by a masked observer.
      The possible length to adjust, the force required for the adjustment, and the
      degree of any adhesions were also evaluated. RESULTS: In the control group,
      adjustment was impossible in all of the five eyes at 1, 2, and 3 postoperative
      weeks, respectively. In the Surgi Wrap group, adjustment was possible in four of
      10 eyes at 1 week after surgery, in two of 10 eyes at 2 weeks after surgery, and
      in none of the 10 eyes at 3 weeks after surgery. CONCLUSION: The use of Surgi
      Wrap could delay adjustment in some of the eyes up to 1 or 2 weeks after surgery.
      Surgi Wrap could be helpful for short-term delayed adjustment in rabbit eyes.

PMID- 16084790
TI  - Macular hole development in fellow eyes of patients with unilateral macular hole.
AB  - PURPOSE: To determine the incidence of developing an idiopathic full-thickness
      macular hole in fellow eyes that have vitreofoveal attachments and perifoveal
      vitreous detachment in patients with unilateral idiopathic macular hole. DESIGN:
      Retrospective cross-sectional observational study. METHODS: The fellow eyes of
      201 patients with full-thickness macular holes were examined by optical coherence
      tomography (OCT). A subset of 58 fellow eyes with vitreofoveal attachments and
      perifoveal vitreous detachment was observed during follow-up, and the changes in
      the vitreofoveal attachment within 24 months from the initial OCT examination
      were investigated. RESULTS: In the 58 eyes, the vitreofoveal relationship changed
      in 27 eyes. Among the 27 eyes, three eyes developed a full-thickness macular
      hole, and the other 24 eyes developed a posterior vitreous detachment only over
      the fovea or a complete posterior vitreous detachment without macular hole
      formation. The vitreofoveal relationship did not change in 31 eyes during the 24
      month period. CONCLUSION: From an analysis of the changes in the vitreoretinal
      relationship identified by OCT, three (11%) of 27 fellow eyes in patients with
      unilateral idiopathic macular hole developed a full-thickness macular hole.

PMID- 16084791
TI  - [Internal herniation through a mesenteric defect after Roux-en-Y anastomosis].
AB  - We report a case of entire of small bowel necrosis due to internal herniation
      through a mesenteric rent around the Roux-en-Y anastomosis. For prevention of
      internal herniation around the Roux-en-Y limb, secure closing of the mesenteric
      is recommended. Nevertheless, the consequences of a mesenteric closing defect are
      rarely reported. Necrosis of the entire small has never been described yet.

PMID- 16084792
TI  - [The new therapies of the peritoneal carcinomatosis should induce new surgical
      attitudes].

PMID- 16084798
TI  - Possible role of superoxide dismutases in the yeast Saccharomyces cerevisiae
      under respiratory conditions.
AB  - We have analyzed the activity of antioxidant and tricarboxylic acid cycle enzymes
      as well as protein carbonyl content in budding yeast Saccharomyces cerevisiae
      cells grown in medium with glycerol using wild-strain cells and defective mutants
      in superoxide dismutases (SODs). The present report demonstrates that the
      activity of catalase, glucose-6-phosphate dehydrogenase, glutathione reductase,
      isocitrate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase, on
      average, was lower in the strains lacking SODs than that in the parental strain.
      On the other hand, under conditions used in this study, the content of carbonyl
      groups in proteins was relatively higher in the wild type as compared with SOD
      defective strains. It may be suggested that in vivo SOD can demonstrate
      protective as well as pro-oxidant properties, and the final result depends on
      particular conditions.

PMID- 16084799
TI  - Membrane association and activity of 15/16-membered peptide antibiotics:
      zervamicin IIB, ampullosporin A and antiamoebin I.
AB  - Permeabilization of the phospholipid membrane, induced by the antibiotic peptides
      zervamicin IIB (ZER), ampullosporin A (AMP) and antiamoebin I (ANT) was
      investigated in a vesicular model system. Membrane-perturbing properties of these
      15/16 residue peptides were examined by measuring the K(+) transport across
      phosphatidyl choline (PC) membrane and by dissipation of the transmembrane
      potential. The membrane activities are found to decrease in the order
      ZER>AMP>>ANT, which correlates with the sequence of their binding affinities. To
      follow the insertion of the N-terminal Trp residue of ZER and AMP, the
      environmental sensitivity of its fluorescence was explored as well as the
      fluorescence quenching by water-soluble (iodide) and membrane-bound (5- and 16
      doxyl stearic acids) quenchers. In contrast to AMP, the binding affinity of ZER
      as well as the depth of its Trp penetration is strongly influenced by the
      thickness of the membrane (diC(16:1)PC, diC(18:1)PC, C(16:0)/C(18:1)PC,
      diC(20:1)PC). In thin membranes, ZER shows a higher tendency to transmembrane
      alignment. In thick membranes, the in-plane surface association of these
      peptaibols results in a deeper insertion of the Trp residue of AMP which is in
      agreement with model calculations on the localization of both peptide molecules
      at the hydrophilic-hydrophobic interface. The observed differences between the
      membrane affinities/activities of the studied peptaibols are discussed in
      relation to their hydrophobic and amphipathic properties.

PMID- 16084800
TI  - Failure to complete a functional restoration program for chronic musculoskeletal
      disorders: a prospective 1-year outcome study.
AB  - OBJECTIVE: To compare comprehensively the likelihood of various socioeconomically
      relevant outcomes between functional restoration completers and noncompleters,
      while simultaneously identifying risk factors for noncompletion. DESIGN: A
      prospective cohort study of patients with chronic disabling occupational
      musculoskeletal disorders (CDOMD). SETTING: Chronic pain management facility.
      PARTICIPANTS: A total of 1440 patients with CDOMD were consecutively divided into
      2 groups-one with 303 patients who did not complete the prescribed treatment
      program (noncompleters [NC]) and a second with 1137 patients who did
      (completers). INTERVENTION: The Interdisciplinary Functional Restoration:
      Rehabilitation program. MAIN OUTCOME MEASURES: Validated questionnaires about
      pain, disability, and depression were added to results of a structured 1-year
      posttreatment telephone interview on socioeconomic outcomes covering work status,
      health utilization, recurrent injury claims, and resolution of financial
      disputes. RESULTS: The 1-year posttreatment socioeconomic outcomes were most
      striking. The NC group was 7 times more likely to have postrehabilitation surgery
      in the same area, and nearly 7 times more likely to have more than 30 visits to a
      new health provider in persistent health care-seeking efforts. The NC group also
      had only half the rates of work return and work retention, being 9.7 times less
      likely to have returned to any type of work, and 7 times less likely to have
      retained work at the end of the year. Regression analysis also revealed that work
      return, surgery in a compensable injured area, more health care utilization from
      a new provider, and more overall health care utilization (>30 visits) were most
      reliably predicted by whether the rehabilitation program was completed.
      CONCLUSIONS: This large prospective study determined that noncompleters of
      interdisciplinary tertiary rehabilitation for CDOMDs had comparatively poor
      socioeconomic outcomes in the year after discharge from treatment, especially on
      work status and health utilization outcomes. These outcomes are of great
      relevance to societal, medical, and indemnity costs and future worker
      productivity. Several risk factors of possible importance in identifying
      potential noncompleters early in the treatment program were identified that may
      yield more effective interventions tailored to maintain compliance and decrease
      the percentage of drop-outs.

PMID- 16084801
TI  - Initial psychometric assessment of a functional oral intake scale for dysphagia
      in stroke patients.
AB  - OBJECTIVE: To report on the development and psychometric evaluation of a clinical
      scale to document change in functional oral intake of food and liquid in stroke
      patients. DESIGN: Validity and reliability study. SETTING: Tertiary care,
      academic medical center, metropolitan stroke unit. PARTICIPANTS: Acute stroke
      patients (N=302). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Interrater reliability, validity, and sensitivity to change assessments were
      completed on a 7-point ordinal scale-the Functional Oral Intake Scale (FOIS)
      developed to document the functional level of oral intake of food and liquid in
      stroke patients. Interrater reliability was drawn from FOIS ratings applied to
      dietary information from patient medical charts. Consensual validity was
      estimated by rankings from judges against predefined scale scores. Criterion
      validity was evaluated by comparison to the Modified Rankin Scale, the Modified
      Barthel Index, and Mann Assessment of Swallowing Ability. Cross-validation was
      assessed via comparison to 2 physiologic measures of swallowing function. Change
      in functional oral intake over time was assessed descriptively by applying the
      scale to dietary information from a cohort of 302 acute stroke patients followed
      up for 6 months. RESULTS: Interrater reliability was high, with perfect agreement
      on 85% of ratings. Kappa statistics ranged from .86 to .91. Consensual validity
      was high (.90). Criterion validity was high at onset and 1 month poststroke.
      Significant associations were identified between the FOIS and stroke handicap
      scales. The FOIS was significantly associated with 2 physiologic measures of
      swallowing. Scores on the FOIS from the cohort of stroke patients showed a shift
      toward increased oral intake over a 6-month period. CONCLUSIONS: The FOIS had
      adequate reliability, validity, and sensitivity to change in functional oral
      intake. These findings suggest that the FOIS may be appropriate for estimating
      and documenting change in the functional eating abilities of stroke patients over
      time.

PMID- 16084802
TI  - Racial differences in activities of daily living limitation onset in older adults
      with arthritis: a national cohort study.
AB  - OBJECTIVE: To investigate factors that predict the onset of limitations in
      activities of daily living (ADLs) in adults 65 years old or older who have
      arthritis, in order to develop public health programs for minorities (African and
      Hispanic Americans) and white Americans. DESIGN: Longitudinal cohort study.
      SETTING: National probability sample. PARTICIPANTS: Older adults with arthritis
      (N=3541) who participated in the 1998 and 2000 Health and Retirement Study
      interviews and who had no baseline ADL limitations. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: Onset of ADL limitations was identified from
      reports of 1 or more ADL task limitations at 2-year follow-up. RESULTS: Onset is
      most frequent among African Americans (24.4%), followed by Hispanics (22.2%), and
      whites (16.9%). Race specific multivariate analysis showed that the strongest
      risk factor predicting onset of limitations across all racial and ethnic groups
      is physical limitations. Low household income was significant for older
      minorities but not for whites. Comorbid cardiovascular disease was a unique
      multivariate risk factor among African Americans. CONCLUSIONS: Physical
      limitation is a strong risk factor for ADL limitation onset that is shared by all
      racial and ethnic groups. Early identification and treatment of physical
      limitations may prevent the onset of ADL limitations and thus improve quality of
      life. Race specific public health interventions should be considered to reduce
      the development of ADL limitations among older adults with arthritis.

PMID- 16084803
TI  - The relative benefits of endurance and strength training on the metabolic factors
      and muscle function of people with type 2 diabetes mellitus.
AB  - OBJECTIVE: To compare the effects of a 4-month strength training (ST) versus
      aerobic endurance training (ET) program on metabolic control, muscle strength,
      and cardiovascular endurance in subjects with type 2 diabetes mellitus (T2D).
      DESIGN: Randomized controlled trial. SETTING: Large public tertiary hospital.
      PARTICIPANTS: Twenty-two T2D participants (11 men, 11 women; mean age +/-
      standard error, 56.2+/-1.1 y; diabetes duration, 8.8+/-3.5 y) were randomized
      into a 4-month ST program and 17 T2D participants (9 men, 8 women; mean age,
      57.9+/-1.4 y; diabetes duration, 9.2+/-1.7 y) into a 4-month ET program.
      INTERVENTIONS: ST (up to 6 sets per muscle group per week) and ET (with an
      intensity of maximal oxygen consumption of 60% and a volume beginning at 15 min
      and advancing to a maximum of 30 min 3x/wk) for 4 months. MAIN OUTCOME MEASURES:
      Laboratory tests included determinations of blood glucose, glycosylated
      hemoglobin (Hb A1c), insulin, and lipid assays. RESULTS: A significant decline in
      Hb A1c was only observed in the ST group (8.3%+/-1.7% to 7.1%+/-0.2%, P=.001).
      Blood glucose (204+/-16 mg/dL to 147+/-8 mg/dL, P<.001) and insulin resistance
      (9.11+/-1.51 to 7.15+/-1.15, P=.04) improved significantly in the ST group,
      whereas no significant changes were observed in the ET group. Baseline levels of
      total cholesterol (207+/-8 mg/dL to 184+/-7 mg/dL, P<.001), low-density
      lipoprotein cholesterol (120+/-8 mg/dL to 106+/-8 mg/dL, P=.001), and
      triglyceride levels (229+/-25 mg/dL to 150+/-15 mg/dL, P=.001) were significantly
      reduced and high-density lipoprotein cholesterol (43+/-3 mg/dL to 48+/-2 mg/dL,
      P=.004) was significantly increased in the ST group; in contrast, no such changes
      were seen in the ET group. CONCLUSIONS: ST was more effective than ET in
      improving glycemic control. With the added advantage of an improved lipid
      profile, we conclude that ST may play an important role in the treatment of T2D.

PMID- 16084804
TI  - The relation between annular disruption on computed tomography scan and pressure
      controlled diskography.
AB  - OBJECTIVE: To analyze the relation between annular disruption determined by
      computed tomography (CT) scan and diskographic findings using pressure-controlled
      manometric diskography. DESIGN: Cross-sectional using prospectively gathered
      data. SETTING: Ambulatory spine intervention unit. SPECIMENS: Two hundred seventy
      nine disks from 86 patients (55 men, 31 women) who were referred for diskography
      of suspected chronic diskogenic low back pain. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: The grade of annular disruption was rated using CT
      diskography and fluoroscopic imaging as follows: 0 (no disruption); 1 (extension
      into the inner third of the annulus); 2 (extension into the middle third of the
      annulus); 3 (extension into the outer third of the annulus); 4 (circumferential
      extension with a >30 degrees arc at the disk center); and 5 (contrast media
      leakage into the outer space). Diskography was performed via a pressure
      controlled manometric technique using an injection rate of .05 mL/s and a
      restricted total volume of 3.5 mL. Pain was rated on a 0 to 10 numeric rating
      scale (NRS). Criteria for symptomatic disks included provocation of patient
      concordant pain (NRS score, > or =6/10) at 50psi or less above opening pressure,
      with 3.5 mL or less of total volume. Symptomatic disks were classified as "low
      pressure sensitive" or "high pressure sensitive" based on the pressure level that
      evoked pain. Disks classified as low pressure sensitive required an NRS score of
      6 out of 10 or higher at 15 psi or less above opening pressure. Disks classified
      as high pressure sensitive required an NRS score of 6 out of 10 or higher at
      pressures within a range of 15 to 50 psi. RESULTS: The numbers of disks at each
      annular disruption grade were 19 (6.8%) at grade 0, 29 (10.4%) at grade 1, 35
      (12.5%) at grade 2, 42 (15.1%) at grade 3, 69 (24.7%) at grade 4, and 85 (30.5%)
      at grade 5. A total of 93 disks met the criteria for a symptomatic disk. The
      extent of annular disruption and the rate of symptomatic disks correlated
      significantly (P<.001). The highest symptomatic disk rate was observed in grade 4
      disks. Of 93 symptomatic disks, 88 (94.6%) showed annular disruption of grade 3
      or greater. Disks with grades 0 to 2 and grades 3 to 5 annular disruption
      differed significantly when the mean NRS relative to intradiskal pressure was
      compared (P<.001). Comparing the disk type of symptomatic disks at each annular
      disruption grade, there was a decreasing trend of low pressure sensitive disks
      relative to the extent of annular disruption (62.5% at grade 3, 39.4% at grade 4,
      34.2% at grade 5). CONCLUSIONS: Annular disruption reaching the outer annulus
      fibrosus is a key factor in pain generation. Disk morphology, including annular
      disruptions extending beyond the outer annulus, may permit increased diskography
      specificity.

PMID- 16084805
TI  - Gait analysis in a challenging environment differentiates between fallers and
      nonfallers among older patients with peripheral neuropathy.
AB  - OBJECTIVE: To identify differences in gait based on fall history among a group of
      older subjects with peripheral neuropathy (PN) in 2 environments: standard (SE)
      (smooth surface, normal lighting) and challenging (CE) (irregular surface, low
      lighting). DESIGN: Observational, case-control study of PN subjects with and
      without a history of falling in the previous year. SETTING: A biomechanical
      laboratory. PARTICIPANTS: Forty-two subjects (mean age, 64.7+/-9.8 y; 20 [47.6%]
      women), including 22 (52.4%) with a history of at least 1 fall in the previous
      year. INTERVENTION: Subjects walked in the SE and CE while kinematic data were
      obtained. MAIN OUTCOME MEASURES: Step width variability, step time variability,
      step width-to-step length ratio, step length, and step time and speed (with step
      length and speed normalized for height) in the SE and CE. RESULTS: In the SE,
      gait parameters of subjects with and without a history of falls did not differ
      significantly. However, in the CE, subjects with a history of falls had increased
      step time variability (P=.001). Moreover, significant interactions between
      environment and fall status were identified: in the CE, subjects with a history
      of falls had greater increases in step time variability (P=.010) and step width
      to-step length ratio (P=.009) and greater decreases in step length (P=.007) and
      speed (P=.045) than did subjects with no fall history. CONCLUSIONS: Analysis of
      gait in the CE and adjustment to the CE from the SE effectively identified gait
      characteristics associated with falls in an older PN population, whereas analysis
      of gait in the SE did not. PN-associated gait dysfunction is more sensitively
      detected on an irregular rather than on a flat surface.

PMID- 16084806
TI  - Use of ultrasound to increase effectiveness of isokinetic exercise for knee
      osteoarthritis.
AB  - OBJECTIVE: To investigate the effects of ultrasound (US) in isokinetic muscle
      strengthening exercises on functional status of patients with knee osteoarthritis
      (OA). DESIGN: Effectiveness of isokinetic muscle strengthening exercises for
      treatment of periarticular soft tissue disorders was compared with and without
      pulsed and continuous US. SETTING: Outpatient exercise program in a Taiwan
      medical university hospital. PARTICIPANTS: One hundred twenty subjects with
      bilateral knee OA (Altman grade II). INTERVENTION: Subjects were randomized
      sequentially into 1 of 4 groups. Group I received isokinetic muscular
      strengthening exercises, group II received isokinetic exercise and continuous US,
      group III received isokinetic exercise and pulsed US treatment, and group IV was
      the control group. MAIN OUTCOME MEASURES: Therapeutic effects of isokinetic
      exercise were evaluated by changes in ambulation speed and the Lequesne index. In
      addition, changes in knee range of motion (ROM), visual analog scale for pain,
      and muscle peak torques during knee flexion and extension were compared.
      Compliance in each group was recorded. RESULTS: Each treated group had increased
      muscle peak torques and significantly reduced pain and disability after treatment
      and at follow-up. However, only patients in groups II and III had significant
      improvement in ROM and ambulation speed after treatment. Fewer participants in
      group III discontinued treatment due to knee pain during exercise. Patients in
      group III also showed the greatest increase in walking speed and decrease in
      disability after treatment and at follow-up. Gains in muscular strength in 60
      degrees /s angular velocity peak torques were also noted in groups II and III.
      However, group III showed the greatest muscular strength gains with 180 degrees
      /s angular velocity peak torques after treatment and follow-up. CONCLUSIONS: US
      treatment could increase the effectiveness of isokinetic exercise for functional
      improvement of knee OA, and pulsed ultrasound has a greater effect than
      continuous US.

PMID- 16084807
TI  - Reduced ambulatory activity after stroke: the role of balance, gait, and
      cardiovascular fitness.
AB  - OBJECTIVES: To determine ambulatory activity in a sample of community-dwelling
      people with chronic hemiparetic stroke and to examine whether deficits in balance
      and gait and cardiovascular and metabolic fitness are key determinants of
      ambulatory activity levels. DESIGN: Descriptive correlational. SETTING: Home and
      community. PARTICIPANTS: Twenty-eight men and 22 women (N=50) over the age 45
      years with more than 6 months of hemiparetic gait after ischemic stroke.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Ambulatory activity (total
      daily step activity), mobility deficit severity (Berg Balance Scale [BBS] scores,
      timed 10-m walks), and cardiovascular fitness (energy costs of hemiparetic gait,
      peak exercise capacity [VO2peak]). RESULTS: Mean ambulatory activity profiles
      were extremely low (2837 steps/d vs reported 5000-6000 steps/d in sedentary older
      adults). Ambulatory activity levels were strongly associated with BBS scores
      (r=.581, P<.001) and self-selected floor walking velocity (r=.554, P<.001).
      Participants also had profound cardiovascular deconditioning (mean VO2peak,
      11.7+/-2.8 mL.kg(-1).min(-1)). The energy costs of hemiparetic gait were high
      (8.7+/-1.7 mL.kg(-1).min(-1)), representing 76% of physiologic fitness reserve.
      Although the relationships of economy of gait and VO2peak to ambulatory activity
      was not statistically significant, both the VO2peak and the physiologic fitness
      reserve, as expressed by fractional utilization, were strongly related to balance
      (r=.374, P=.02; r=-.430, P< .01, respectively.) The BBS predicted 30% of the
      variance in ambulatory activity. CONCLUSIONS: Ambulatory activity levels and
      cardiovascular fitness in patients with chronic stroke are extremely low.
      Mobility deficits, particularly in balance, are associated with low ambulatory
      activity. Balance-related inactivity may be an important factor in
      deconditioning. Further studies are needed to better understand whether task
      oriented exercise enhances balance and whether increases in daily ambulatory
      activity yield improved cardiovascular fitness in chronic stroke survivors.

PMID- 16084808
TI  - The effectiveness of body weight-supported gait training and floor walking in
      patients with chronic stroke.
AB  - OBJECTIVE: To compare body weight-supported exercise on a gait trainer with
      walking exercise overground. DESIGN: Randomized controlled trial. SETTING:
      Rehabilitation hospital. PARTICIPANTS: Forty-five ambulatory patients with
      chronic stroke. INTERVENTIONS: Patients were randomized to 3 groups: (1) gait
      trainer exercise with functional electric stimulation (GTstim), (2) gait trainer
      exercise without stimulation (GT), and (3) walking overground (WALK). All
      patients practiced gait for 15 sessions during 3 weeks (each session, 20 min),
      and they received additional physiotherapy 55 minutes daily. MAIN OUTCOME
      MEASURES: Ten-meter walk test (10MWT), six-minute walk test (6MWT), lower-limb
      spasticity and muscle force, postural sway tests, Modified Motor Assessment Scale
      (MMAS), and FIM instrument scores were recorded before, during, and after the
      rehabilitation and at 6 months follow-up. RESULTS: The mean walking distance
      using the gait trainer was 6900+/-1200 m in the GTstim group and 6500+/-1700 m in
      GT group. In the WALK group, the distance was 4800+/-2800 m, which was less than
      the walking distance obtained in the GTstim group (P=.027). The body-weight
      support was individually reduced from 30% to 9% of the body weight over the
      course of the program. In the pooled 45 patients, the 10MWT (P<.001), 6MWT
      (P<.001), MMAS (P<.001), dynamic balance test time (P<.001), and test trip
      (P=.005) scores improved; however, no differences were found between the groups.
      CONCLUSIONS: Both the body weight-supported training and walking exercise
      training programs resulted in faster gait after the intensive rehabilitation
      program. Patients' motor performance remained improved at the follow-up.

PMID- 16084809
TI  - A trial of neuropsychologic rehabilitation in mild-spectrum traumatic brain
      injury.
AB  - OBJECTIVE: To test the effectiveness of a neuropsychologic rehabilitation program
      consisting of psychotherapy and cognitive remediation in the treatment of the
      affective and neuropsychologic sequelae of mild-spectrum traumatic brain injury
      (TBI). DESIGN: Single-blind randomized, wait-listed controlled trial, with
      repeated measures and multiple baselines. SETTING: Outpatient clinic in northern
      New Jersey. PARTICIPANTS: Twenty persons with persisting complaints after mild
      and moderate TBI (11 in treatment group, 9 controls). INTERVENTIONS: The
      experimental group received both 50 minutes of individual cognitive-behavioral
      psychotherapy and 50 minutes of individual cognitive remediation, 3 times a week
      for 11 weeks. The control group was wait-listed and received treatment after
      conclusion of follow-up. MAIN OUTCOME MEASURES: Symptom Check List-90R General
      Symptom Index, plus scales of depression, anxiety, coping, attention, and
      neuropsychologic functioning. RESULTS: Compared with the control group, the
      treatment group showed significantly improved emotional functioning, including
      lessened anxiety and depression. Most significant improvements in emotional
      distress were noted at 1 month and 3 months posttreatment. Performance on a
      measure of divided auditory attention also improved, but no changes were noted in
      community integration scores. CONCLUSIONS: Cognitive behavioral psychotherapy and
      cognitive remediation appear to diminish psychologic distress and improve
      cognitive functioning among community-living persons with mild and moderate TBI.

PMID- 16084810
TI  - The longitudinal relation between physical capacity and wheelchair skill
      performance during inpatient rehabilitation of people with spinal cord injury.
AB  - OBJECTIVE: To study the longitudinal relation between physical capacity and
      wheelchair skill performance in subjects with spinal cord injury (SCI) during
      rehabilitation. DESIGN: Observational prospective cohort study. Measurements were
      taken 3 times during subjects' rehabilitation. SETTING: Eight rehabilitation
      centers in the Netherlands. PARTICIPANTS: Ninety-seven subjects with SCI.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Parameters of physical
      capacity were upper-extremity muscle strength (manual muscle test [MMT] sum
      score), peak oxygen uptake, and peak power output (POpeak). The Wheelchair
      Circuit consists of 8 wheelchair skills and results in 3 test scores: ability,
      performance time, and physical strain. RESULTS: POpeak was related to all 3
      scores of the Wheelchair Circuit, and the MMT sum score was related to the
      ability score and the performance time score. The results indicate that (1)
      subjects with higher values of POpeak and/or the MMT sum score had better scores
      on the Wheelchair Circuit than subjects with lower values and (2) when a subject
      increased his/her POpeak and/or MMT sum score, this was associated with better
      wheelchair skill scores. CONCLUSIONS: There is a significant longitudinal
      relation between wheelchair skill performance and POpeak and MMT sum score during
      the rehabilitation of people with SCI. To optimize wheelchair skill performance,
      attention should be directed toward manual wheelchair exercise training and
      strength training of the upper body.

PMID- 16084811
TI  - Ventilation efficiency and pulmonary function after a wheelchair interval
      training program in subjects with recent spinal cord injury.
AB  - OBJECTIVE: To study the effect of a wheelchair interval-training program on the
      ventilatory function of subjects with recent spinal cord injury (SCI). DESIGN:
      Evaluation trial before and after a training program. SETTING: Center of
      reeducation and university hospital. PARTICIPANTS: Six subjects (5 men, 1 woman)
      hospitalized after a recent SCI. INTERVENTION: On a wheelchair ergometer,
      subjects with SCI performed 30 minutes of interval training 3 times a week for 6
      weeks. The training program was part of their reeducation program. MAIN OUTCOME
      MEASURES: Spirometric values at rest and dynamic ventilatory responses were
      studied before and after this training program with a spirometric test, a maximal
      exercise test that increased by 5W every 2 minutes, and a submaximal test.
      RESULTS: Spirometric values at rest did not change after training. At maximal
      exercise, peak ventilation (Vepeak, 7.5%), peak breathing frequency (f peak) (
      13.4%), peak tidal volume (Vtpeak +28.9%), and the ventilatory reserve (12.9%)
      improved after training. The oxygen cost of Ve decreased significantly (-20%)
      after training. We observed for the wheelchair tests that, at the same workload
      after training, Ve and f decreased and Vt increased. CONCLUSIONS: After 6 weeks
      of our interval-training program in subjects with recent SCI, the increase of Vt
      and the decrease of oxygen cost of Ve indicated better ventilatory efficiency.

PMID- 16084812
TI  - Patients' and relatives' reports of disturbances 9 months after stroke:
      subjective changes in physical functioning, cognition, emotion, and behavior.
AB  - OBJECTIVE: To quantify the frequency of physical, cognitive, emotional, and
      behavioral changes as reported by patients and relatives after a stroke and to
      determine their degree of agreement. DESIGN: Follow-up study of 172 stroke
      patients to a mean of 9.8 months poststroke and 143 relatives interviewed
      separately with a questionnaire. SETTING: Home-based stroke patients.
      PARTICIPANTS: The 172 patients (107 men, 68 women) were a subset of 229 patients
      enrolled in a previous study. Their mean age +/- standard deviation was 55.3+/
      10.9 years (age range, 18-70 y). Other participants were 143 relatives (mostly
      spouses; 43 men, 100 women) had a mean age of 52.4+/-12.2 years. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURE: Structured interview using a questionnaire.
      RESULTS: The overall percentage of frequency of different disturbances was
      comparable between patients' and relatives' reports. However, the degree of
      agreement between patients and their relatives tended to be low. Several possible
      explanations for this finding are considered, including the potential role of
      residuals of anosognosia in this stroke population. CONCLUSIONS: Educating
      families and rehabilitation specialists about the frequency of disturbances and
      possible reasons for different opinions between patients and families may provide
      useful information for therapeutic interventions.

PMID- 16084813
TI  - Disability and quality of life in Canadian aboriginal and non-aboriginal diabetic
      lower-extremity amputees.
AB  - OBJECTIVE: To compare and contrast disability and quality of life (QOL) in
      Aboriginal and non-Aboriginal subjects with diabetes who had lower-extremity
      amputation (LEA) and were living in urban and rural communities in Canada.
      DESIGN: Descriptive study using an interviewer-administered questionnaire and
      hospital medical record review. SETTING: Tertiary care center. PARTICIPANTS:
      Forty-four diabetic subjects (minimum age, 18 y) not receiving dialysis,
      including 21 Aboriginal (8 urban, 13 rural) and 23 non-Aboriginal (16 urban, 7
      rural) subjects. Subjects were living in their current residence and had
      undergone LEA above the level of the ankle 6 months or more before interview.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Qualitative and
      quantitative data about symptoms, impairment, and QOL. RESULTS: Aboriginal
      subjects were younger than non-Aboriginal subjects at the time of diabetes
      diagnosis (Aboriginal, 42+/-10 y; non-Aboriginal, 52+/-14 y; P<.005) and first
      major LEA (Aboriginal, 57+/-7 y; non-Aboriginal, 64+/-11 y; P<.015). All subjects
      received rehabilitation after amputation. More rural non-Aboriginal subjects
      (83%) used their prosthesis both in and outside the home for all movements than
      other subjects (P<.048). Rural non-Aboriginal subjects had the lowest and urban
      non-Aboriginal subjects had the highest frequency of walking-aid use outside the
      home. Assistance with personal care was required by a minority of subjects, but
      assistance with daily housework was required by the majority of subjects.
      Qualitative analysis revealed that participants were, in most cases, comfortable
      with their postamputation life. CONCLUSIONS: Although the majority of
      participants in this study generally felt satisfied with their current status,
      major functional changes were noted after LEA that had a large negative impact on
      QOL.

PMID- 16084814
TI  - Decreased muscle strength and mobility of the neck in patients with rheumatoid
      arthritis and atlantoaxial disorders.
AB  - OBJECTIVE: To compare neck muscle strength and mobility of the cervical spine in
      rheumatoid arthritis (RA) patients with and without atlantoaxial (AA) disorders
      (anterior atlantoaxial subluxation [AAS], AA impaction). DESIGN: Clinical cross
      sectional study. SETTING: Outpatient rheumatology and rehabilitation clinics in a
      Finnish hospital. PARTICIPANTS: Patients with RA (N=124; mean age +/- standard
      deviation, 62+/-12y [corrected]) on a waiting list for orthopedic surgery. Thirty
      (24%) patients presented with AA disorders (16 with anterior AAS, 8 with AA
      impaction, 6 with a combination of anterior AAS and AA impaction). INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Neck function was measured by isometric
      neck strength and mobility tests, neck pain by a visual analog scale, erosion of
      the hands and feet by radiography, and the patients' function by the Health
      Assessment Questionnaire (HAQ). RESULTS: Maximal neck muscle strength against
      flexion, extension, and rotation was lower in patients with AA disorders compared
      with the other patients in both women (P=.012) and men (P=.017). Mobility was
      lowest in the AA impaction group in all measured directions (P<.001). Peripheral
      erosive disease was more frequent in the group with AA disorders. They also had
      longer disease duration and were more disabled (HAQ) than the other patients.
      CONCLUSIONS: Neck muscle strength is significantly decreased in patients with AA
      disorders. Mobility of the cervical spine is most limited in patients with AA
      impaction, but can be normal in cases with solitary anterior AAS.

PMID- 16084815
TI  - Assessing arm and hand function after stroke: a validity test of the hierarchical
      scoring system used in the motor assessment scale for stroke.
AB  - OBJECTIVE: To evaluate the validity of the scoring hierarchy for the 3 upper-limb
      items on the Motor Assessment Scale (MAS). DESIGN: Application of Rasch analysis
      to 3 independent measurement scales, each representing the upper-arm function,
      hand movements, and advanced hand activities items of the MAS. SETTING: Inpatient
      and outpatient occupational therapy (OT) programs in a department of
      rehabilitation of an urban hospital center. PARTICIPANTS: One hundred patients
      (67 men, 33 women; average age, 54.3+/-14.4 y; average time since stroke onset,
      104 d) attending OT for stroke rehabilitation. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURE: The MAS for stroke (upper-arm function, hand movements, and
      advanced hand activities sections). RESULTS: Rasch analysis provided support for
      the validity of hierarchical scoring criteria for the upper-arm scale. This
      analysis, however, identified inconsistencies in the hierarchical scoring
      criteria for the hand function and advanced hand activities scales and, when
      considering measurement error, only small differences in difficulty level between
      several behavioral criteria. CONCLUSIONS: The findings lead to suggestions for
      changes in the behavioral criteria hierarchy for upper-limb items on the MAS and
      highlight the importance of using statistical analyses to test the validity of
      proposed hierarchies of behavioral criteria in functional assessments.

PMID- 16084816
TI  - Test-retest reliability, validity, and sensitivity of the Chedoke arm and hand
      activity inventory: a new measure of upper-limb function for survivors of stroke.
AB  - OBJECTIVES: To estimate the test-retest reliability and validity of the Chedoke
      Arm and Hand Activity Inventory (CAHAI) and to test whether the CAHAI was more
      sensitive to change in upper-limb function than the Impairment Inventory of the
      Chedoke-McMaster Stroke Assessment (CMSA) and the Action Research Arm Test
      (ARAT). DESIGN: Construct validation process. SETTING: Inpatient/outpatient
      rehabilitation facilities. PARTICIPANTS: Stratified sample of 39 survivors of
      stroke: 24 early (mean age, 71.4 y; mean days poststroke, 27.3) and 15 chronic
      (mean age, 64.0 y; mean days poststroke, 101.7). INTERVENTION: Regular therapy.
      MAIN OUTCOME MEASURES: Intraclass correlation coefficients (ICCs), receiver
      operating characteristic (ROC), standard error of measurement, and correlation
      coefficients. RESULTS: High interrater reliability was established with an ICC of
      .98 (95% confidence interval [CI], .96-.99). The minimal detectable change score
      was 6.3 CAHAI points. Higher correlations were obtained between the CAHAI and the
      ARAT and CMSA scores compared with the CMSA shoulder pain scores (1-sided,
      P=.001). Areas under the ROC curves were as follows: CAHAI, .95 (95% CI, 0.87
      1.00); CMSA, .76 (95% CI, .61-.92); and ARAT, .88 (95% CI, 0.76-1.00).
      CONCLUSIONS: High interrater reliability and convergent and discriminant cross
      sectional validity were established for the CAHAI. The CAHAI is more sensitive to
      clinically important change than the ARAT.

PMID- 16084817
TI  - Choice-based evaluation for the improvement of upper-extremity function compared
      with other impairments in tetraplegia.
AB  - OBJECTIVES: To assess preference of reconstructive treatment of upper extremities
      in subjects with tetraplegia compared with preference of treatment of 3 other
      impairments and to determine the effect of subjects' characteristics on
      preference of upper-extremity reconstruction. DESIGN: Survey. SETTING: Two
      specialized spinal cord injury centers in the Netherlands. PARTICIPANTS: A
      consecutive sample of 47 patients with tetraplegia in stable condition.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The quality weight of 5
      tetraplegic health states determined with the time trade-off technique and
      expressed as a single value (the "utility") on a scale between 0 (worst possible
      situation) and 1 (best possible situation). RESULTS: The response rate was 92%.
      The utility of tetraplegia +/- standard deviation was .57+/-.30. The utilities of
      tetraplegia without impairment in one of the following functions were .69+/-.33
      for sexuality, .69+/-.33 for standing/walking, .63+/-.31 for bladder and bowel
      function, and .65+/-.32 for upper-extremity function. The differences between
      these utilities and the utility of tetraplegia were significant (P<.05). No
      significant differences were found between the utilities of the impairments.
      Improvement of a specific impairment contributed between 14% and 28% to the
      potential overall gain in the tetraplegic health state utility. CONCLUSIONS: The
      combination of impairments determines the low utility of the tetraplegic health
      state. No priority for improvement of any of the investigated impairments was
      found. This emphasizes the need for the meticulous selection of patients for
      treatment of specific conditions. Further research should try to determine the
      crucial factors in the decision-making process of patients for specific
      interventions.

PMID- 16084818
TI  - Dyspnea during daily activities in chronic spinal cord injury.
AB  - OBJECTIVE: To assess factors associated with breathlessness in chronic spinal
      cord injury (SCI) during daily activities. DESIGN: Cross-sectional survey.
      SETTINGS: Veterans Affairs SCI service and the community. PARTICIPANTS: Four
      hundred forty-one participants 1 or more years post-SCI, and without acute
      illness, were recruited between 1994 and 2003 and were categorized according to
      their ability to walk unassisted, walk with an aid, or to move about by either
      hand-propelled wheelchair or motorized wheelchair (MWC). INTERVENTIONS:
      Assessment of injury extent, respiratory symptoms, cigarette smoking, comorbid
      medical conditions, and spirometry. MAIN OUTCOME MEASURES: Breathlessness during
      talking, eating, or dressing. RESULTS: Breathlessness was more common in MWC
      users (20/85 users, 24%) than in nonusers (20/356, 6%). The main activity
      associated with breathlessness in 15 MWC users was talking (18%). In MWC users,
      the risk of breathlessness was related to lifetime cigarette smoking (odds ratio
      [OR]=1.02; 95% confidence interval [CI], 1.00-1.03 per pack year), and reports of
      chronic cough (OR=7.8; 95% CI, 2.0-32.7), and wheeze (OR=3.5; 95% CI, 1.04-13.6).
      SCI level, percentage of predicted forced vital capacity and forced expiratory
      volume in 1 second, and maximal inspiratory pressures were not related to
      breathlessness. CONCLUSIONS: Breathlessness during selected daily activities
      (most commonly talking) was greatest in SCI participants who were most impaired
      with regard to mobility and was associated with reports of coughing, wheezing,
      and cigarette smoking.

PMID- 16084819
TI  - A pilot study to explore the predictive validity of 4 measures of falls risk in
      frail elderly patients.
AB  - OBJECTIVES: To test the hypothesis that scores on 4 falls risk measures will
      differ significantly in patients reporting recurrent falls compared with those
      who do not; and to explore the validity of each measure to predict such falls
      status. DESIGN: A convenience sample was tested to establish the sensitivity and
      specificity of the Functional Reach Test, Timed Up & Go test, one-leg stance test
      (OLST), and balance subsection of the Performance Oriented Mobility Assessment (B
      POMA). A 12-month retrospective falls history was used to identify recurrent
      fallers. SETTING: A day hospital for the elderly. PARTICIPANTS: Convenience
      sample of 30 day hospital patients. The inclusion criteria were: ability to rise
      from a chair and walk 6m; no severe cognitive impairment or blindness; age 65
      years or older. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Scores on
      the 4 tests and retrospective falls histories. RESULTS: Scores on the B-POMA and
      OLST showed significant differences between fallers and nonfallers (P<.05). An
      OLST time of 1.02 seconds or less (odds ratio [OR]=15.2; 95% confidence interval
      [CI], 1.72-133.95) and B-POMA score of 11 or less (OR=18.5; 95% CI, 2.05-167.79)
      were predictive of day hospital patients having a history of recurrent falls.
      CONCLUSIONS: OLST and B-POMA both have potential as screening tools for risk of
      falls, but this observation requires confirmation in a prospective study.

PMID- 16084820
TI  - The timed up & go test: its reliability and association with lower-limb
      impairments and locomotor capacities in people with chronic stroke.
AB  - OBJECTIVES: To examine test-retest reliability of the Timed Up & Go (TUG) test,
      its ability to differentiate subjects with chronic stroke from healthy elderly
      subjects, and its associations with ankle plantarflexor spasticity, ankle muscle
      strength, gait performance, and distance walked in 6 minutes in subjects with
      chronic stroke. DESIGN: Cross-sectional study. SETTING: University-based
      rehabilitation center in Hong Kong, China. PARTICIPANTS: Ten healthy elderly
      subjects and 11 subjects with chronic stroke. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Time taken to complete the TUG test was recorded. Plantarflexor
      spasticity and ankle muscle strength were assessed, respectively, by the
      Composite Spasticity Scale and a load-cell together with electromyography. Gait
      parameters and walking endurance were measured respectively by walkway system
      (GAITRite II) and 6-minute walk test. Intraclass correlation coefficients (ICCs)
      were calculated as measures of reliability, and all correlation analyses were
      conducted using Spearman correlation coefficients. RESULTS: The TUG test showed
      excellent reliability (ICC>.95). Subjects with chronic stroke had significantly
      more spastic and weaker plantarflexors, slower walking speeds, and poorer walking
      endurance when compared with healthy elderly subjects (all P<.003). The strength
      of the affected ankle plantarflexors (rho=-.860, P<.01), gait parameters (rho
      range, .620-.900; P<.05), and walking endurance (rho=-.960, P<.01) correlated
      with TUG scores. CONCLUSIONS: The TUG scores were reliable, were able to
      differentiate the patients from the healthy elderly subjects, and correlated well
      with plantarflexor strength, gait performance, and walking endurance in subjects
      with chronic stroke.

PMID- 16084821
TI  - Reliability of biomechanical spasticity measurements at the elbow of people
      poststroke.
AB  - OBJECTIVE: To determine the minimum number of measurements required to obtain a
      reliable estimate of upper-extremity spasticity using biomechanic assessment
      across multiple testing trials and dates. DESIGN: Single-center, longitudinal
      study with repeated measurements of spastic upper-extremity torque measures taken
      1 week apart. SETTING: A hospital-based laboratory with an isokinetic testing
      system. PARTICIPANTS: Sixteen subjects more than 6 months poststroke with upper
      extremity spasticity. INTERVENTION: Elbow flexor hypertonia was assessed with a
      custom-made manipulandum attached to a 6-axis load cell and a Biodex System 3
      isokinetic testing machine. Movements into extension were imposed at 4 speeds: 6
      degrees /s, 30 degrees /s, 60 degrees /s, and 90 degrees /s. MAIN OUTCOME
      MEASURES: The resistive torque and electromyographic response to these imposed
      movements were measured. The torque response at the slowest speed (6 degrees /s)
      was attributed solely to the passive elements of the elbow and was subtracted
      from the torque response at the higher speeds (30 degrees /s, 60 degrees /s, 90
      degrees /s), leaving only reflex torque. The reflex torques at 30 degrees /s, 60
      degrees /s, and 90 degrees /s were used for further analysis. Peak torque, peak
      joint stiffness, and onset angle of reflex torque responses were found;
      repeatability and daily variability of these measures were statistically
      examined. The variabilities due to the subject, test day, and trial number were
      computed. The overall reliability of each parameter at the 3 higher test speeds
      using different testing schemes was also calculated. RESULTS: Ninety percent
      reliability in the measurement of all parameters was obtained after at least 2
      days of testing during which 3 tests a day were performed. The variability in
      between-subjects measurements was at least 4 times greater than the intertrial
      variability when testing at the highest speeds; daily variability that was up to
      50% of the intersubject variability was also observed. The biomechanic measures
      correlated well with the Ashworth Scale (Spearman rho=.84, P<.005), a clinical
      measure of hypertonia. CONCLUSIONS: We recommend at least 2 test dates to account
      for the daily variability in the spastic reflex response and to ensure reliable
      spasticity measurements.

PMID- 16084822
TI  - The use of a portable muscle tone measurement device to measure the effects of
      botulinum toxin type a on elbow flexor spasticity.
AB  - OBJECTIVE: To use a portable muscle tone assessment device to measure spasticity
      after a botulinum toxin type A (BTX-A) injection. DESIGN: Before-after trial.
      SETTING: Hospital. PARTICIPANTS: Ten chronic stroke patients with upper-limb
      spasticity. INTERVENTION: BTX-A was injected in the biceps brachii. MAIN OUTCOME
      MEASURES: The biomechanic parameters, viscous component, and averaged viscosity
      derived from the acquired reactive resistance and angular displacements, as well
      as the reflex electromyographic threshold of biceps brachii, were used for
      spasticity evaluation. RESULTS: A statistically significant decrease in averaged
      viscosity and a significant increase in reflex electromyographic threshold
      (P<.05) both indicated reduction in spasticity owing to BTX-A intervention. There
      was no clear reflex electromyographic activity detected at lower stretch
      frequencies. CONCLUSIONS: Our portable design allows for the convenient use of
      the device for quantifying spasticity in clinics. All quantitative measurements
      suggest that BTX-A decreases spasticity within 2 weeks of injection. Our portable
      muscle tone measurement device may be useful for the clinical assessment of elbow
      flexor spasticity.

PMID- 16084823
TI  - The effect of wearing a wrist splint on shoulder kinematics during object
      manipulation.
AB  - OBJECTIVES: To test the hypotheses that (1) wearing a flexible wrist splint while
      taking an object from a box increases known postural risk factors for shoulder
      disorders and (2) that the height of the front of the box modulates the effect on
      shoulder kinematics of wearing a wrist splint. DESIGN: A controlled laboratory
      experiment with 2 factors (splint wearing, box height). SETTING: Human
      performance laboratory. PARTICIPANTS: Ten consecutive healthy volunteers (5 men,
      5 women; age range, 19-32 y). INTERVENTIONS: Experimental manipulation of wrist
      immobilization and box height. MAIN OUTCOME MEASURES: Humeral plane of elevation,
      humeral elevation, and humeral axial rotation. RESULTS: Wearing a wrist splint
      increased the maximum humeral elevation angle (P<.001), and the height of the
      barrier also increased the maximum humeral elevation angle (P<.001). The average
      difference in maximum humeral elevation between the splint and the no splint
      conditions was 6.8 degrees . CONCLUSIONS: Wearing a wrist splint while performing
      a job that requires removing objects from a box can increase risk factors for
      shoulder disorders. Workplace analysis should be performed to avoid secondary
      injuries before a patient wearing a wrist splint returns to work.

PMID- 16084824
TI  - Norms for 15- to 34-year-olds for different versions of the finger-to-nose test.
AB  - OBJECTIVES: To develop norms for the time to execute different versions of the
      finger-to-nose test (FNT) and to determine the effects of different testing
      procedures on performance in people aged 15 to 34 years. DESIGN: Cross-sectional.
      SETTING: Research center. PARTICIPANTS: Healthy subjects (149 men, 148 women; age
      range, 15-34 y) participated, and 36 men and 36 women were included in each of
      the 4 age categories studied (15-19 y, 20-24 y, 25-29 y, 30-34 y). Participants
      performed, in random order, 5 forms of the test in 2 positions (sitting, supine)
      with the right and left upper limbs (ULs). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURE: Time (in seconds) to complete 5 cycles of movement. RESULTS:
      Test version and side of UL were found to affect performances; right-sided
      performances were faster than left-sided. Performances did not vary significantly
      (P>.001) with sex or among age categories; therefore, the results are presented
      for the group. Mean performances varied from 3.44 to 4.29 seconds. Subsequent
      analysis of variance (with data for each UL) showed main effects for testing
      position (sitting > lying) and eye condition (eyes open > eyes closed). Versions
      were strongly interrelated (.85<r<.98). CONCLUSIONS: Norms for the time to
      execute different FNT versions were developed for both ULs for healthy people
      ages 15 to 34 years.

PMID- 16084825
TI  - Intra- and intersubject reliability of abductor pollicis brevis muscle motor map
      characteristics with transcranial magnetic stimulation.
AB  - OBJECTIVE: To determine consistency in motor maps of the abductor pollicis brevis
      (APB) muscle using transcranial magnetic stimulation (TMS) with conventional and
      close-spaced surface electrode recording placements. DESIGN: Nonrandom
      convenience sample. SETTING: TMS laboratory. PARTICIPANTS: Eleven participants
      without any known neurologic disorders. INTERVENTIONS: The left hemisphere of
      right-hand-dominant subjects was mapped using TMS at each of 2 sessions,
      separated by 1 to 8 weeks. MAIN OUTCOME MEASURES: Measurements at each session
      included the resting motor threshold, active site locations and average motor
      response amplitude for active sites, normalized map volume, and center of gravity
      (COG) for both electrode array configurations. RESULTS: The normalized map volume
      was larger for the conventional electrode placement than for the close electrode
      placement (4.23 cm2 vs 3.44 cm2, P=.010). Resting motor threshold was higher for
      the close-spaced than for the conventional-spaced electrodes (48.36% vs 46.59%,
      P=.028). No statistical difference was found between sessions and within
      electrode placements for the normalized map volume, for resting motor threshold,
      or for the mean motor amplitude of the most active site for each map. No
      statistical difference was observed for the COG distance between electrode
      placements. CONCLUSIONS: This study revealed differences between close-spaced and
      conventional-spaced surface electrode placement for TMS motor map volumes and for
      resting motor thresholds. The motor maps for the APB muscle were reliably
      reproducible between sessions for each electrode array.

PMID- 16084826
TI  - Gait evaluation of an automatic stance-control knee orthosis in a patient with
      postpoliomyelitis.
AB  - OBJECTIVE: To determine gait differences in a subject ambulating with a knee
      ankle-foot orthosis (KAFO) with a locked knee joint versus an automatic stance
      control knee joint. DESIGN: Single-subject crossover design. SETTING: Tertiary
      rehabilitation facility with a motion analysis laboratory. PARTICIPANT: A 61-year
      old ambulatory male volunteer with postpoliomyelitis walking with a stance
      control KAFO. INTERVENTIONS: Instrumented gait analysis and Physiological Cost
      Index in the locked knee and stance-control modes. MAIN OUTCOME MEASURE:
      Differences in gait parameters. RESULTS: On the braced limb, stance-control mode
      showed a near-normal knee flexion wave in swing, reduced pelvic retraction and
      rotational excursion, and improved hip power generation. On the nonbraced limb,
      the stance-control mode allowed elimination of vaulting, reduction in abnormal
      ankle and hip power generation, increased knee power absorption, and more typical
      quadriceps activation. There was a trend toward improved energy efficiency in the
      stance-control mode. CONCLUSIONS: Use of a stance-control knee joint in a KAFO
      appears to improve gait biomechanics and improve energy efficiency compared with
      a locked knee.

PMID- 16084827
TI  - Evidence-based cognitive rehabilitation: updated review of the literature from
      1998 through 2002.
AB  - OBJECTIVE: To update the previous evidence-based recommendations of the Brain
      Injury Interdisciplinary Special Interest Group of the American Congress of
      Rehabilitation Medicine for cognitive rehabilitation of people with traumatic
      brain injury (TBI) and stroke, based on a systematic review of the literature
      from 1998 through 2002. DATA SOURCES: PubMed and Infotrieve literature searches
      were conducted using the terms attention, awareness, cognition, communication,
      executive, language, memory, perception, problem solving, and reasoning combined
      with each of the terms rehabilitation, remediation, and training. Reference lists
      from identified articles were reviewed and a bibliography listing 312 articles
      was compiled. STUDY SELECTION: One hundred eighteen articles were initially
      selected for inclusion. Thirty-one studies were excluded after detailed review.
      Excluded articles included 14 studies without data, 6 duplicate publications or
      follow-up studies, 5 nontreatment studies, 4 reviews, and 2 case studies
      involving diagnoses other than TBI or stroke. DATA EXTRACTION: Articles were
      assigned to 1 of 7 categories reflecting the primary area of intervention:
      attention; visual perception; apraxia; language and communication; memory;
      executive functioning, problem solving and awareness; and comprehensive-holistic
      cognitive rehabilitation. Articles were abstracted and levels of evidence
      determined using specific criteria. DATA SYNTHESIS: Of the 87 studies evaluated,
      17 were rated as class I, 8 as class II, and 62 as class III. Evidence within
      each area of intervention was synthesized and recommendations for practice
      standards, practice guidelines, and practice options were made. CONCLUSIONS:
      There is substantial evidence to support cognitive-linguistic therapies for
      people with language deficits after left hemisphere stroke. New evidence supports
      training for apraxia after left hemisphere stroke. The evidence supports
      visuospatial rehabilitation for deficits associated with visual neglect after
      right hemisphere stroke. There is substantial evidence to support cognitive
      rehabilitation for people with TBI, including strategy training for mild memory
      impairment, strategy training for postacute attention deficits, and interventions
      for functional communication deficits. The overall analysis of 47 treatment
      comparisons, based on class I studies included in the current and previous
      review, reveals a differential benefit in favor of cognitive rehabilitation in 37
      of 47 (78.7%) comparisons, with no comparison demonstrating a benefit in favor of
      the alternative treatment condition. Future research should move beyond the
      simple question of whether cognitive rehabilitation is effective, and examine the
      therapy factors and patient characteristics that optimize the clinical outcomes
      of cognitive rehabilitation.

PMID- 16084828
TI  - The course of functional status and muscle strength in patients with late-onset
      sequelae of poliomyelitis: a systematic review.
AB  - OBJECTIVES: To review systematically studies of late-onset polio sequelae on the
      course of functional status and muscle strength over time and to identify
      prognostic factors of change. DATA SOURCES: We conducted a computerized
      literature search up to July 2004 in MEDLINE, EMBASE, CINAHL, Web of Science,
      PsychInfo, and the Cochrane controlled trial register using the key words:
      postpolio, postpoliomyelitis, postpoliomyelitis syndrome, post poliomyelitis
      muscular atrophy, and poliomyelitis. STUDY SELECTION: Reports were selected by 1
      reviewer if the study involved subjects with a history of poliomyelitis, the
      outcome measures described functional status or muscle strength, and follow-up
      was for at least 6 months. DATA EXTRACTION: Studies were summarized with regard
      to population, design, sample size, outcome measures, results, and methodologic
      scores. Overlap in populations between studies was checked. DATA SYNTHESIS: Of 71
      potentially relevant studies, 19 were included (2 on functional status, 15 on
      muscle strength, 2 on both muscle strength and functional status). Two studies on
      the course of functional status had sufficient quality and reported inconsistent
      results. Four studies on the course of muscle strength had sufficient quality.
      Two studies reported a decline in strength and 2 reported no change. Decline in
      strength was only reported in studies with a follow-up period longer than 2
      years. One study reported extent of paresis as a prognostic factor for change in
      perceived physical mobility. CONCLUSIONS: Conclusions cannot be drawn from the
      literature with regard to the functional course or prognostic factors in late
      onset polio sequelae. The rate of decline in muscle strength is slow, and
      prognostic factors have not yet been identified. Long-term follow-up studies with
      unselected study populations and age-matched controls are needed, with specific
      focus on prognostic factors.

PMID- 16084829
TI  - Pectoral nerve conduction studies: technique in healthy subjects and evaluation
      of brachial plexopathy.
AB  - OBJECTIVE: To define the optimal nerve conduction study (NCS) technique of the
      pectoral nerves and evaluate its clinical utility. DESIGN: Prospective
      electrophysiologic study with healthy controls. SETTING: Electrophysiologic
      laboratory in a large general hospital. PARTICIPANTS: Thirty healthy controls and
      10 patients with cervical root or brachial plexus pathologies. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: Correlation of pectoral NCS with
      electromyography and magnetic resonance imaging. RESULTS: For pectoral NCS, the
      mean values +/- standard deviation of onset latency, amplitude, and interside
      amplitude ratio (ratio of smaller over larger amplitude) were 2.01+/-0.22 ms,
      11.75+/-2.21 mV, and .95+/-.04 mV, respectively. Subject age correlated
      significantly with both onset latency (r=.46, P<.001) and amplitude (r=-.34,
      P<.008). All 5 patients with brachial plexopathy had amplitude ratios below the
      normal limit of controls (.87). However, this was not seen for all 5 patients
      with cervical spondylotic radiculopathy. CONCLUSIONS: The pectoral NCS technique
      is feasible in healthy subjects. It is useful when differentiating brachial
      plexopathy from cervical root lesions.

PMID- 16084830
TI  - Cortical reorganization of hand motor function to primary sensory cortex in
      hemiparetic patients with a primary motor cortex infarct.
AB  - OBJECTIVE: To show cortical reorganization in hemiparetic patients with a primary
      motor cortex (M1) infarct including the precentral knob by using functional
      magnetic resonance imaging (fMRI). DESIGN: Case-control. SETTING: Outpatient
      clinics in the rehabilitation department of a university hospital. PARTICIPANTS:
      Two stroke patients and 20 control subjects. INTERVENTIONS: By using fMRI, we
      evaluated the hand motor function of 2 hemiparetic stroke patients, who had made
      some recovery from complete paralysis of the affected hand, and 20 control
      subjects. MAIN OUTCOME MEASURES: fMRI was performed by using the blood oxygen
      level-dependent technique at 1.5 T with a standard head coil. The motor task
      paradigm consisted of hand grasp-release movements. RESULTS: The contralateral
      primary sensorimotor cortex was activated by the hand movements of the control
      subjects and of the unaffected side of the 2 patients. Only the contralateral
      (infarct side) primary sensory cortex (S1) was activated by the movements of the
      affected hand of the 2 patients, a result that was not observed in the control
      subjects or with the unaffected hand in the stroke patients. CONCLUSIONS: The
      hand motor function associated with the infarcted M1 in our patients was
      reorganized into the S1. These results suggest cortical reorganization in
      patients with an M1 infarct.

PMID- 16084831
TI  - Deinococcus radiodurans strain R1 contains N6-methyladenine in its genome.
AB  - Methylation of DNA is known to be involved in DNA repair mechanisms in bacteria.
      Deinococcus radiodurans strain R1 on exposure to high radiation undergoes
      significant DNA damage, which is repaired without mutations. However, the
      presence of modified nucleotides has not been reported in its genome. We report
      here the detection of N6-methyladenine in the genome of D. radiodurans strain R1
      using immunochemical techniques. This N6-methyladenine is not a part of GATC
      restriction-modification system. D. radiodurans cell extract also exhibited a DNA
      adenine methyltransferase activity which was reduced in the early post
      irradiation recovery phase.

PMID- 16084832
TI  - Hyperglycemia-induced activation of human T-lymphocytes with de novo emergence of
      insulin receptors and generation of reactive oxygen species.
AB  - Upon activation by phytohemagglutine (PHA), T-lymphocytes (T-cells) express
      receptors for growth factors, insulin, IGF-1 and IL2 and become insulin
      sensitive. Diabetic ketoacidosis (DKA) is associated with in vivo emergence of
      these growth factor receptors without incubation with PHA. As DKA consists of
      multiple metabolic alterations, in addition to hyperglycemia, we investigated the
      in vitro effect of different concentrations of glucose (5, 15, and 30 mM) in
      isolated CD4 of human T-cells at various time intervals (0, 24, 48, and 72 h).
      Hyperglycemia, but not euglycemia, resulted in de novo emergence of growth factor
      receptors in a dose- and time-dependent fashion. The activation was also
      associated with incremental changes in GLUT 4, IRS-1, proinflammatory cytokines,
      and oxidative stress components. We propose that activation of T-cells with
      development of insulin receptors in hyperglycemic conditions may serve as a
      mechanism for control of glucose entry into these cells, thus, protecting them
      against glucose toxicity.

PMID- 16084833
TI  - Molecular identification of wheat endoxylanase inhibitor TAXI-II and the
      determinants of its inhibition specificity.
AB  - Wheat grains contain Triticum aestivum xylanase inhibitor (TAXI) proteins which
      inhibit microbial xylanases, some of which are used in cereal based food
      industries. These inhibitors may play a role in plant defence. Among the TAXI
      isoforms described so far, TAXI-II displays a deviating inhibition specificity
      pattern. Here, we report on the molecular identity of TAXI-II and the basis of
      its inhibition specificity. Three candidate TAXI-II encoding sequences were
      isolated and recombinantly expressed in Pichia pastoris. To identify TAXI-II, the
      resulting proteins were tested against glycoside hydrolase family (GHF) 11
      xylanases of Aspergillus niger (ANX) and Bacillus subtilis (BSX). One of these
      proteins (rTAXI-IB) inhibited both enzymes, like natural TAXI-I. The other
      candidates (rTAXI-IIA and rTAXI-IIB) showed an inhibition pattern typical for
      natural TAXI-II, only clearly inhibiting BSX. Comparative analysis of these
      highly similar sequences with distinct inhibition activity patterns, combined
      with information on the structural basis for ANX inhibition by TAXI-I [S. Sansen,
      C.J. De Ranter, K. Gebruers, K. Brijs, C.M. Courtin, J.A. Delcour, A. Rabijns,
      Structural basis for inhibition of Aspergillus niger xylanase by Triticum
      aestivum xylanase inhibitor-I, J. Biol. Chem. 279 (2004) 36022-36028], indicated
      a crucial role for Pro294 of TAXI-IIA and Gln376 of TAXI-IIB in determining the
      reduced inhibition activity towards ANX. Consequently, single point mutants rTAXI
      IIA[P294L] and rTAXI-IIB[Q376H], both displaying the Leu/His combination
      corresponding to TAXI-I, were able to inhibit ANX. These results show that TAXI
      II inhibition specificity bears on the identity of two key residues at positions
      294 and 376, which are involved in the interaction at the -2 glycon subsite and
      the active site of GHF 11, respectively.

PMID- 16084834
TI  - An artificial electron donor supported catalytic cycle of Pseudomonas putida
      cytochrome P450cam.
AB  - Putidaredoxin (PdX), the physiological effector of cytochrome P450cam (P450cam),
      serves to gate electron transfer into oxy-P450cam during the catalytic cycle of
      the enzyme. Redox-linked structural changes in PdX are necessary for the
      effective P450cam turnover reaction. PdX is believed to be difficult to be
      replaced by an artificial electron donor in the reaction pathway of P450cam. We
      demonstrate that the catalytic cycle of wild-type P450cam can be supported in the
      presence of an artificial reductant, potassium ferrocyanide. Upon rapid mixing of
      ferrocyanide ion with P450cam, we observed an intermediate with spectral features
      characteristic of compound I. The rate constant for the formation of compound I
      in the presence of ferrocyanide supported reaction cycle was found to be
      comparable to the ones observed for H2O2 supported compound I formation in wild
      type P450cam, but was much lower than those observed for classical peroxidases.
      The results presented in this paper form the first kinetic analysis of this
      intermediate for an artificial electron-driven P450cam catalytic pathway in
      solution.

PMID- 16084835
TI  - A structural study towards the understanding of the interactions of SoxY, SoxZ,
      and SoxB, leading to the oxidation of sulfur anions via the novel global sulfur
      oxidizing (sox) operon.
AB  - Microbial redox reactions of inorganic sulfur compounds, mainly the sulfur
      anions, are one of the vital reactions responsible for the environmental sulfur
      balance. These reactions are mediated by phylogenetically diverse prokaryotes,
      which also take part in the extraction of metal ions from their sulfur containing
      ores. The sulfur oxidizing gene cluster (sox) of alpha-Proteobacteria comprises
      of at least 16 genes, forming two transcriptional units, viz., soxSRT and
      soxVWXYZABCDEFGH. SoxY is known to be a sulfur covalently binding protein, which
      binds sulfur anions (such as sulfate) to form SoxY-thiocysteine-S-sulfate, the
      first covalently bound sulfur adduct in the novel global sulfur anion oxidation
      cycle. SoxZ, a sulfur compound chelating protein, binds to SoxY forming a complex
      to which SoxB, a sulfate thiol-esterase, binds and ultimately cleaves the sulfur
      adduct. We employed homology modeling to construct the three-dimensional
      structures of the SoxY, SoxZ, and SoxB from Paracoccus pantotrophus. With the
      help of docking and molecular dynamics studies we have identified the residues of
      SoxY, SoxZ, and SoxB involved in the interaction. The probable mechanisms of the
      binding of SoxY with sulfate as well as the removal of sulfate from the SoxYZ
      complex are also established. Our study provides a rational basis to illustrate
      the molecular mechanism of the biochemistry of sulfur anion oxidation reactions
      by these industrially important organisms.

PMID- 16084836
TI  - Development of a bi-cistronic baculovirus expression vector by the Rhopalosiphum
      padi virus 5' internal ribosome entry site.
AB  - A bi-cistronic baculovirus transfer vector was constructed based on the 5'UTR
      internal ribosome entry site (IRES) of the Rhopalosiphum padi virus (RhPV).
      Recombinant baculoviruses containing the red fluorescent protein gene and green
      fluorescent protein gene flanking the RhPV 5'UTR IRES can simultaneously produce
      dual fluorescence in recombinant virus-infected Spodoptera frugiperda 21 cells
      (Sf21) under the control of a polyhedrin promoter. Quantization by fluorescence
      spectrophotometry of the fluorescent proteins produced in Sf21 cells indicated
      that the translational efficacy of the RhPV 5'UTR IRES was about 3-fold weaker
      than cap-dependent translation. We also demonstrated that recombinant
      baculoviruses containing the human interferon-gamma gene (IFN-gamma) and green
      fluorescent protein gene flanking the RhPV 5'UTR IRES can produce IFN-gamma
      proteins as well as green fluorescent proteins. These results suggest that the
      RhPV IRES can be used in the development of bi-cistronic baculovirus expression
      vectors for production of heterologous multiprotein complexes or can be combined
      with selection markers to facilitate applications of baculovirus expression
      systems.

PMID- 16084837
TI  - The effects of UCP-1 polymorphisms on obesity phenotypes among Korean female
      subjects.
AB  - Three SNPs of UCP-1 including A-3826G, A-1766G, and Ala64Thr (G+1068A) were
      genotyped among 453 overweight Korean female subjects recruited from an obesity
      clinic. Four common haplotypes with frequency greater than 0.04 were constructed
      with three SNPs. For an accurate evaluation of the effects of UCP-1 polymorphism
      on body fat accumulation, all subjects were tested using computerized tomography
      to measure the cross-sectional fat tissue areas at abdominal and distal part of
      the body. By statistical analyses, ht4[GAA] showed a significant association with
      decreased abdominal fat tissue area (P=0.02, dominant model), fat tissue area at
      thigh (P=0.008, dominant model), body fat mass (P=0.002, dominant model), and
      waist-to-hip ratio (P=0.01, dominant model). In addition, ht3[GAG] was associated
      with the accelerated reduction of waist-to-hip ratio and body fat mass by very
      low calorie diet among subjects who finished one-month-weight control program
      (P=0.05-0.006).

PMID- 16084838
TI  - Mood disorders in the medically ill: scientific review and recommendations.
AB  - OBJECTIVE: The purpose of this review is to assess the relationship between mood
      disorders and development, course, and associated morbidity and mortality of
      selected medical illnesses, review evidence for treatment, and determine needs in
      clinical practice and research. DATA SOURCES: Data were culled from the 2002
      Depression and Bipolar Support Alliance Conference proceedings and a literature
      review addressing prevalence, risk factors, diagnosis, and treatment. This review
      also considered the experience of primary and specialty care providers, policy
      analysts, and patient advocates. The review and recommendations reflect the
      expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of
      epidemiology and mechanistic studies were included, as were open-label and
      randomized, controlled trials on treatment of depression in patients with medical
      comorbidities. Data on study design, population, and results were extracted for
      review of evidence that includes tables of prevalence and pharmacological
      treatment. The effect of depression and bipolar disorder on selected medical
      comorbidities was assessed, and recommendations for practice, research, and
      policy were developed. CONCLUSIONS: A growing body of evidence suggests that
      biological mechanisms underlie a bidirectional link between mood disorders and
      many medical illnesses. In addition, there is evidence to suggest that mood
      disorders affect the course of medical illnesses. Further prospective studies are
      warranted.

PMID- 16084839
TI  - Anterior cingulate activation and error processing during interferon-alpha
      treatment.
AB  - BACKGROUND: There has been increasing interest in the role of immunologic
      processes, notably cytokines, in the development of behavioral alterations,
      especially in medically ill patients. Interferon (IFN)-alpha is notorious for
      causing behavioral symptoms, including depression, fatigue, and cognitive
      dysfunction, and has been used to investigate the effects of cytokines on the
      brain. METHODS: In the present study we assessed the effects of low-dose IFN
      alpha on brain activity, using functional magnetic resonance imaging during a
      task of visuospatial attention in patients infected with hepatitis C virus (HCV).
      RESULTS: Despite endorsing symptoms of impaired concentration and fatigue, IFN
      alpha-treated patients (n = 10) exhibited task performance and activation of
      parietal and occipital brain regions similar to that seen in HCV-infected control
      subjects (n = 11). Interestingly, however, in contrast to control subjects, IFN
      alpha-treated patients exhibited significant activation in the dorsal part of the
      anterior cingulate cortex (ACC), which highly correlated with the number of task
      related errors. No such correlation was found in control subjects. CONCLUSIONS:
      Consistent with the role of the ACC in conflict monitoring, ACC activation during
      IFN-alpha administration suggests that cytokines might increase processing
      conflict or reduce the threshold for conflict detection, thereby signaling the
      need to exert greater mental effort to maintain performance. Such alterations in
      ACC activity might in turn contribute to cytokine-induced behavioral changes.

PMID- 16084840
TI  - Cortical magnetic resonance imaging findings in familial pediatric bipolar
      disorder.
AB  - BACKGROUND: Morphometric magnetic resonance imaging (MRI) studies of pediatric
      bipolar disorder (BD) have not reported on gray matter volumes but have reported
      increased lateral ventricular size and presence of white matter hyperintensities
      (WMH). We studied gray matter volume, ventricular-to-brain ratios (VBR), and
      number of WMH in patients with familial, pediatric BD compared with control
      subjects. METHODS: Twenty subjects with BD (aged 14.6 +/- 2.8 years; 4 female)
      according to the Washington University in St. Louis Kiddie Schedule for Affective
      Disorders and Schizophrenia, each with a parent with BD, and 20 age-, gender-,
      and intelligence quotient-matched healthy control subjects (aged 14.1 +/- 2.8
      years; 4 female) were scanned at 3 T. Most subjects were taking psychotropic
      medications. A high-resolution T1-weighted spoiled gradient echo three
      dimensional MRI sequence was analyzed by BrainImage for volumetric measurements,
      and T2-weighted images were read by a neuroradiologist to determine presence of
      WMH. RESULTS: After covarying for age and total brain volume, there were no
      significant differences between subjects with BD and control subjects in volume
      of cerebral (p = .09) or prefrontal gray matter (p = .34). Subjects with BD did
      not have elevated numbers of WMH or greater VBR when compared with control
      subjects. CONCLUSIONS: Children and adolescents with familial BD do not seem to
      have decreased cerebral grey matter or increased numbers of WMH, dissimilar to
      findings in adults with BD. Gray matter decreases and development of WMH might be
      later sequelae of BD or unique to adult-onset BD.

PMID- 16084841
TI  - Prenatal anxiety predicts individual differences in cortisol in pre-adolescent
      children.
AB  - BACKGROUND: Animal studies suggest that prenatal stress is associated with long
      term disturbance in hypothalamic-pituitary-adrenal (HPA) axis function, but
      evidence in humans is lacking. This study examined the long-term association
      between prenatal anxiety and measures of diurnal cortisol at age 10 years.
      METHODS: Measures of cortisol were collected at awakening, 30 min after
      awakening, and at 4 pm and 9 pm on 3 consecutive days in a sample of 10-year-olds
      (n = 74) from the Avon Longitudinal Study of Parents and Children, a prospective
      longitudinal cohort study of mothers and children on whom measures of anxiety and
      depression were collected in pregnancy and the postpartum period. Analyses
      examined the links between symptoms of prenatal anxiety and multiple indicators
      of cortisol, an index of HPA axis functioning. RESULTS: Prenatal anxiety was
      significantly associated with individual differences in awakening and afternoon
      cortisol after accounting for obstetric and sociodemographic risk (partial
      correlations were .32 and .25, p < .05). The effect for awakening cortisol
      remained significant after controlling for multiple postnatal assessments of
      maternal anxiety and depression. CONCLUSIONS: This study provides the first human
      evidence that prenatal anxiety might have lasting effects on HPA axis functioning
      in the child and that prenatal anxiety might constitute a mechanism for an
      increased vulnerability to psychopathology in children and adolescents.

PMID- 16084842
TI  - Phosphorylation of 9-beta-D-arabinofuranosylguanine monophosphate by Drosophila
      melanogaster guanylate kinase.
AB  - Nucleoside monophosphate kinases have an important role in the synthesis of
      nucleotides that are required for cellular metabolism. These enzymes are also
      important for the phosphorylation of nucleoside- and nucleotide analogs used in
      cancer and anti-viral therapy. We report the cDNA cloning and characterization of
      a 23 kDa guanylate kinase from Drosophila melanogaster (Dm-GUK). The predicted
      amino acid sequence was 58% identical to the human guanylate kinase and the
      enzyme was shown to phosphorylate GMP and dGMP with ATP as phosphate donor. The
      monophosphates of the deoxyguanosine analogs 2',2'-difluorodeoxyguanosine (dFdG)
      and 9-beta-D-arabinofuranosylguanine (araG) were also shown to be phosphorylated
      by the enzyme. We used the enzyme to reconstitute the complete in vitro three
      step phosphorylation pathway for the conversion of dGuo and araG to the
      corresponding triphosphates.

PMID- 16084844
TI  - Successful bridging strategy based on ICH E5 guideline for drugs approved in
      Japan.

PMID- 16084845
TI  - A commentary on the American Society for Clinical Pharmacology and Therapeutics
      position statement on dietary supplement safety and regulation.

PMID- 16084846
TI  - Placental transfer of antiretroviral drugs.

PMID- 16084847
TI  - Functional role of P-glycoprotein in the human blood-placental barrier.
AB  - OBJECTIVE: In vitro and animal experiments suggest that P-glycoprotein forms a
      functional barrier between maternal and fetal blood circulation in the placenta,
      thus protecting the fetus from exposure to xenobiotics during pregnancy. In this
      study we aimed to characterize the role of P-glycoprotein in the blood-placental
      barrier by use of dually perfused human placenta. METHODS: Twenty-eight human
      placentas were obtained after delivery, and both the maternal side and the fetal
      side were perfused for 2 hours. Saquinavir was used as a probe drug for P
      glycoprotein-dependent active transfer, and PSC833 (valspodar) or GG918 was used
      as an inhibitor of P-glycoprotein function in a maternal-to-fetal and fetal-to
      maternal perfusion setting. Genotyping for ABCB1 (C3435T and G2677A/T)
      polymorphism and quantification of P-glycoprotein expression were done for each
      placenta. RESULTS: The fetal-to-maternal transfer of saquinavir was 108-fold
      higher (P = .003) compared with transfer from the maternal to the fetal
      direction. Preperfusion with PSC833 increased the placental transfer of
      saquinavir by 7.9-fold (P < .001), and preperfusion with GG918 increased it by
      6.2-fold (P < .001). The end-perfusion transfer (percentage) of saquinavir at 120
      minutes was 11-fold (P < .001) and 6-fold (P < .001) higher in placentas
      preperfused with PSC833 and GG918, respectively, compared with control. However,
      PSC833 had no effect on the transfer of saquinavir from the fetal to the maternal
      direction (P = .79). P-glycoprotein expression was correlated with the PSC833
      induced change in the saquinavir transfer (r = 0.75, P = .086). ABCB1
      polymorphism did not affect the PSC833- or GG918-induced change in the saquinavir
      transfer. CONCLUSIONS: P-glycoprotein has a major functional role in the human
      blood-placental barrier but a negligible role in the removal of substances from
      the fetal circulation to maternal blood. Pharmacologic blockade of P-glycoprotein
      function can lead to disruption of the blood-placental barrier and increase the
      transfer of P-glycoprotein substrates to the fetal side by several-fold, which
      may be a noteworthy mechanism for teratogenicity.

PMID- 16084848
TI  - Intracellular and plasma pharmacokinetics of nevirapine in human immunodeficiency
      virus-infected individuals.
AB  - BACKGROUND AND OBJECTIVE: Plasma concentrations of nevirapine have been linked to
      human immunodeficiency virus (HIV) treatment outcome. However, because the site
      of action of nevirapine is within HIV-infected cells, intracellular
      concentrations may better relate to antiviral exposure. Investigation of factors
      that alter the intracellular pharmacokinetics of nevirapine may also aid in our
      understanding of therapeutic failure. Our objective was to determine
      intracellular (or cell-associated) nevirapine concentrations over the full dosing
      interval and to relate protein binding and P-glycoprotein (P-gp) expression to
      intracellular exposure. METHODS: Plasma and peripheral blood mononuclear cells
      were isolated from blood samples taken from 10 HIV-infected patients at 0, 2, 4,
      8, and 12 hours after dosing. Intracellular and plasma (total and unbound)
      concentrations were determined by liquid chromatography-tandem mass spectrometry,
      and the ratios of intracellular to total plasma exposure (area under the
      concentration-time curves) were calculated. P-gp expression was measured by flow
      cytometry. RESULTS: The median intracellular accumulation ratio was 0.005 (range,
      0.001-0.054) and remained unchanged over the dosing interval. There was an
      association between higher plasma concentrations and lower cellular
      concentrations of nevirapine (total r(2) = 0.62, P = .007). There was no
      relationship between percent unbound nevirapine and intracellular nevirapine.
      There was a correlation between higher plasma nevirapine exposure and higher P-gp
      expression (r(2) = 0.77, P = .03), whereas intracellular nevirapine exposure
      decreased with higher P-gp expression (r(2) = 0.62, P = .01). CONCLUSIONS: The
      intracellular accumulation of nevirapine was low, did not change over the dosing
      interval, and was not related to protein binding. In this small study, cells with
      higher P-gp expression had lower cellular concentrations of nevirapine. Further
      studies are required to explore the influx and efflux transporter profile of this
      drug.

PMID- 16084849
TI  - Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel
      blockers.
AB  - BACKGROUND: Hypertension is an important modifiable cardiac risk factor in human
      immunodeficiency virus (HIV)-infected patients. Calcium channel blockers are
      substrates of cytochrome P450 3A and are commonly prescribed for hypertension. We
      evaluated potential bidirectional pharmacokinetic interactions between calcium
      channel blockers and coadministered indinavir and ritonavir. METHODS: Healthy HIV
      seronegative subjects received 120 mg diltiazem daily or 5 mg amlodipine daily
      for days 1 to 7 and 20 to 26. All subjects received 100 mg ritonavir and 800 mg
      indinavir every 12 hours on days 8 to 26. Twenty-four-hour pharmacokinetic
      collection was performed on days 7 and 26, with 12-hour collection on day 19.
      RESULTS: Indinavir plus ritonavir increased the median amlodipine area under the
      curve from 0 to 24 hours (AUC) by 89.8%, from 122 to 230 ng.h/mL (n = 18, P <
      .0001), and increased the median diltiazem AUC by 26.5%, from 800 to 1060 ng.h/mL
      (n = 13, P = .06). Of 13 subjects, 2 (15%) had greater than 4-fold increases in
      diltiazem AUC. Desacetyldiltiazem AUC increased by 102.2% (P = .001), and
      desmethyldiltiazem AUC decreased by 27.4% (P = .01). Neither amlodipine nor
      diltiazem affected steady-state AUCs of the protease inhibitors. No serious
      cardiovascular adverse effects were observed. CONCLUSIONS: Indinavir plus
      ritonavir increases the AUCs of both amlodipine and diltiazem, which may result
      in an increased response. If coadministration is indicated, amlodipine or
      diltiazem should be initiated at low doses with careful titration to response and
      side effects.

PMID- 16084850
TI  - Rifampin markedly decreases and gemfibrozil increases the plasma concentrations
      of atorvastatin and its metabolites.
AB  - BACKGROUND: The pharmacokinetic interactions of the widely used statin
      atorvastatin with fibrates and enzyme inducers are not known. Therefore we
      studied the effects of rifampin (INN, rifampicin) and gemfibrozil on the
      pharmacokinetics of atorvastatin. METHODS: Two randomized crossover studies were
      conducted. In study 1, 10 healthy volunteers took 600 mg rifampin or placebo once
      daily for 5 days. On day 6, they ingested a single 40-mg dose of atorvastatin. In
      study 2, 10 healthy volunteers took 600 mg gemfibrozil or placebo twice daily for
      5 days. On day 3, they ingested a single 20-mg dose of atorvastatin. Plasma
      concentrations of atorvastatin (in nanograms per milliliter) and its metabolites
      (in arbitrary units) were measured by liquid chromatography-tandem mass
      spectrometry up to 48 to 72 hours after dosing. RESULTS: Rifampin reduced the
      total area under the plasma concentration-time curve (AUC) of unchanged
      atorvastatin (acid) by 80% (95% confidence interval [CI], 73% to 84%; P < .001),
      that of the active metabolites 2-hydroxyatorvastatin acid by 43% (95% CI, 29% to
      51%; P < .001) and 4-hydroxyatorvastatin acid by 81% (95% CI, 74% to 84%; P <
      .001), and that of their lactones by 93% (95% CI, 90% to 95%), by 61% (95% CI,
      50% to 69%), and by 76% (95% CI, 70% to 81%), respectively (P < .001). The peak
      plasma concentration of 2-hydroxyatorvastatin acid was increased by 68% (95% CI,
      21% to 127%; P = .005) by rifampin. Rifampin shortened (P < .001) the half-lives
      of atorvastatin (by 74%; 95% CI, 67% to 81%) and its metabolites, for example,
      atorvastatin lactone (by 82%; 95% CI, 80% to 85%) and 2-hydroxyatorvastatin acid
      (by 70%; 95% CI, 64% to 78%). Gemfibrozil increased the AUC of atorvastatin (by
      24%; 95% CI, -1% to 50%; P =.059), 2-hydroxyatorvastatin acid (by 51%; 95% CI,
      28% to 70%; P < .001) and its lactone (by 29%; 95% CI, 13% to 53%; P =.003), and
      4-hydroxyatorvastatin acid (by 82%; 95% CI, 60% to 126%; P < .001) and its
      lactone (by 28%; 95% CI, 15% to 51%; P =.001). The half-lives of atorvastatin and
      its lactone metabolites were slightly shortened by gemfibrozil (P < .05).
      CONCLUSIONS: Rifampin markedly decreases and gemfibrozil moderately increases the
      plasma concentrations of atorvastatin and its metabolites. It is advisable to
      increase the dosage of atorvastatin and preferable to administer it in the
      evening to guarantee adequate concentrations during the nighttime rapid
      cholesterol synthesis when rifampin or other potent inducers of cytochrome P450
      3A4 are coadministered. Care is warranted, and only low doses of atorvastatin
      should be used if coadministration with gemfibrozil is needed.

PMID- 16084851
TI  - Pharmacodynamic analysis of tacrolimus and cyclosporine in living-donor liver
      transplant patients.
AB  - BACKGROUND: The calcineurin inhibitors tacrolimus and cyclosporine (INN,
      ciclosporin) have been widely used to prevent allograft rejection after
      transplantation. We investigated pharmacodynamic properties of the 2 drugs and
      their clinical relevance in liver transplantation. METHODS: Forty de novo living
      donor liver transplant patients participated in this study, and they were treated
      with either tacrolimus (N = 30) or cyclosporine (N = 10). We simultaneously
      measured blood drug concentrations and calcineurin phosphatase activity in
      peripheral blood mononuclear cells during the first 14 postoperative days.
      Nephrotoxicity and acute rejection were also examined in relation to the blood
      drug concentrations and calcineurin activity. RESULTS: Calcineurin activity was
      only partially inhibited by tacrolimus concentrations greater than 20 ng/mL,
      although it could be almost completely inhibited by cyclosporine concentrations
      greater than 700 ng/mL. According to a maximum effect model, the population mean
      estimates of the EC(50) (blood concentration that yields a half-maximal effect)
      for tacrolimus and cyclosporine were 26.4 ng/mL (95% confidence interval [CI],
      15.7-37.1 ng/mL) and 200 ng/mL (95% CI, 127-274 ng/mL), respectively. Patients
      with nephrotoxicity in both groups had significantly higher trough concentrations
      compared with those without this adverse event. In addition, patients with acute
      rejection in the tacrolimus group had significantly lower trough concentrations
      and higher calcineurin activity than those without a rejection episode.
      CONCLUSIONS: The inhibitory effects on calcineurin activity in peripheral blood
      mononuclear cells differed between tacrolimus and cyclosporine in living-donor
      liver transplant patients. Pharmacodynamic assessment in combination with blood
      concentration monitoring may be useful for determining the individual therapeutic
      range of tacrolimus and cyclosporine.

PMID- 16084852
TI  - Influence of functional haplotypes in the drug transporter gene ABCB1 on central
      nervous system drug distribution in humans.
AB  - BACKGROUND AND OBJECTIVE: Single nucleotide polymorphisms in the human multidrug
      resistance gene ABCB1 have been reported to be associated with altered expression
      and function of P-glycoprotein, an efflux transporter, expressed at the blood
      brain barrier. To test whether certain ABCB1 haplotypes contribute to
      interindividual differences in central nervous system drug distribution, brain
      distribution of a model P-glycoprotein substrate, the calcium channel inhibitor
      verapamil, was measured by positron emission tomography (PET) in 2 groups of
      healthy volunteers. METHODS: Ten homozygous carriers (cases) of the TTT haplotype
      (3435T, 1236T, and 2677T) and 10 controls homozygous for the wild-type CGC
      haplotype (3435C, 2677G, and 1236C) were administered a mean intravenous bolus of
      412 +/- 114 MBq carbon 11-labeled verapamil containing less than 15 nmol of
      unlabeled verapamil. PET imaging of brain tissue and venous blood sampling were
      performed for 1 hour after dosing. RESULTS: As a measure of brain penetration,
      the ratio of PET area under the time-radioactivity curve (AUC) to plasma AUC was
      calculated from time-radioactivity curves, with a mean ratio of 1.1 +/- 0.3 (SD)
      (95% confidence interval, 0.9-1.3) for cases and 1.1 +/- 0.2 (95% confidence
      interval, 0.9-1.2) for controls, respectively (P = .96). Mean brain AUC values
      were 31.2 +/- 3.9 and 35.7 +/- 5.7 for the TTT and CGC haplotype, respectively (P
      = .11). Plasma AUCs were not significantly different. CONCLUSION: No difference
      in the brain distribution of [(11)C]verapamil could be detected in healthy
      volunteers differing in ABCB1 haplotypes.

PMID- 16084853
TI  - Effect of itraconazole on the pharmacokinetics and pharmacodynamics of
      fexofenadine in relation to the MDR1 genetic polymorphism.
AB  - OBJECTIVE: Our objective was to evaluate the effect of itraconazole, a P
      glycoprotein inhibitor, on the pharmacokinetics and pharmacodynamics of
      fexofenadine, a P-glycoprotein substrate, in relation to the multidrug resistance
      1 gene (MDR1) G2677T/C3435T haplotype. METHODS: A single oral dose of 180 mg
      fexofenadine was administered to 7 healthy subjects with the 2677GG/3435CC (G/C)
      haplotype and 7 with the 2677TT/3435TT (T/T) haplotype. One hour before the
      fexofenadine dose, either 200 mg itraconazole or placebo was administered to the
      subjects in a double-blinded, randomized, crossover manner with a 2-week washout
      period. Histamine-induced wheal and flare reactions were measured to assess the
      effects on the antihistamine response. RESULTS: In the placebo phase,
      pharmacokinetic parameters of fexofenadine showed no statistically significant
      difference between 2 MDR1 haplotypes; the area under the curve from time 0 to
      infinity (AUC(0-infinity)) of fexofenadine in the T/T and G/C groups was 5194.0
      +/- 1910.8 and 4040.4 +/- 1832.2 ng.mL(-1).h(-1), respectively (P = .271), and
      the oral clearance (CL/F) was 530.9 +/- 191.1 and 806.0 +/- 355.3 mL.h(-1).kg(
      1), respectively (P = .096). The disposition of itraconazole, a substrate of P
      glycoprotein, was not significantly different between the 2 haplotypes. After
      itraconazole pretreatment, however, the differences in fexofenadine
      pharmacokinetics became statistically significant; the mean fexofenadine AUC(0
      infinity) in the T/T group was significantly higher than that in the G/C group
      (15,630.6 +/- 5070.0 and 9252.9 +/- 2044.1 ng/mL.h, respectively; P = .007), and
      CL/F of the T/T subjects was lower than that of the G/C subjects (167.0 +/- 33.3
      and 292.3 +/- 42.2 mL.h(-1).kg(-1), respectively; P < .001). Itraconazole
      pretreatment caused more than a 3-fold increase in the peak concentration of
      fexofenadine and the area under the curve to 6 hours compared with the placebo
      phase. This resulted in a significantly higher suppression of the histamine
      induced wheal and flare reactions in the itraconazole pretreatment phase compared
      with those in the placebo phase. CONCLUSION: The effect of MDR1 G2677T/C3435T
      haplotypes on fexofenadine disposition are magnified in the presence of
      itraconazole. Itraconazole pretreatment significantly altered the disposition of
      fexofenadine and thus its peripheral antihistamine effects.

PMID- 16084854
TI  - Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor
      gamma2 gene on rosiglitazone response in type 2 diabetes.
AB  - OBJECTIVE: The aim of this study was to examine the effects of the Pro12Ala
      polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma2 gene
      on the response to rosiglitazone in patients with type 2 diabetes mellitus.
      METHODS: A total of 198 patients with type 2 diabetes mellitus were treated with
      rosiglitazone (4 mg/d) for 12 weeks without a change in previous medications. All
      patients were genotyped for the PPARgamma2 Pro12Ala polymorphism. RESULTS: The
      Ala12 allele frequency was 0.04. Of the 198 patients, 183 had the Pro12Pro
      genotype and 15 had the Pro12Ala genotype. The Ala12Ala genotype was not
      observed. The decrease in fasting plasma glucose level was significantly greater
      in subjects with the Ala12 allele than in those without the allele (50.6 +/- 27.8
      mg/dL versus 24.3 +/- 41.9 mg/dL, P = .026). In addition, the decrease in
      hemoglobin A(1c) level was significantly greater in subjects with the Ala12
      allele than in those without the allele (1.41% +/- 1.47% versus 0.57% +/- 1.16%,
      P = .015). There was a significant difference in the response rate to
      rosiglitazone treatment between the Pro12Pro group and the Pro12Ala variant group
      (43.72% versus 86.67%, P = .002). CONCLUSION: Patients with the Pro12Ala genotype
      in the PPARgamma2 gene had a better therapeutic response to rosiglitazone than
      did patients with the Pro12Pro genotype. The genetic variations in the PPARgamma2
      gene can affect the response to rosiglitazone treatment in patients with type 2
      diabetes mellitus.

PMID- 16084855
TI  - Effect of left prefrontal repetitive transcranial magnetic stimulation on food
      craving.
AB  - BACKGROUND: Dysfunction of the prefrontal cortex is implicated in craving for
      drugs and food. This study explores the effect of prefrontal cortex stimulation
      on food craving. METHODS: In a randomized double-blind parallel group study, 28
      women, who reported frequent cravings for food were exposed to foods that
      typically elicit strong cravings before and after a single session of real or
      sham 10-Hz repetitive transcranial magnetic stimulation to the left dorsolateral
      prefrontal cortex at an intensity of 110% individual motor threshold. RESULTS:
      Self-reported food craving during exposure to the experimental foods remained
      stable before and after real stimulation compared with sham stimulation in which
      cravings increased over the experimental session. Consumption of snack foods
      within a 5-min period after stimulation did not differ between groups.
      CONCLUSIONS: Prefrontal stimulation inhibits the development of craving. A longer
      period of observation is necessary to establish whether there is an effect on
      food consumption.

PMID- 16084856
TI  - Global-local visual processing in schizophrenia: evidence for an early visual
      processing deficit.
AB  - BACKGROUND: Abnormalities in early-stage visual processing might contribute to
      observed higher neurocognitive deficits in schizophrenia, but to date no clear
      link has been established. Schizophrenia has been associated with deficits in the
      magnocellular visual pathway, suggesting a relative bias for processing elemental
      (local) as opposed to configural (global) aspects of a hierarchical stimulus;
      however, global-local paradigm studies in schizophrenia have yielded mixed
      results. METHODS: In the current study, global-local and event-related potential
      (ERP) procedures were concomitantly used to assess temporal and spatial
      characteristics of hierarchical visual stimulus processing abnormalities.
      RESULTS: Patients (n = 24) had slower and less accurate responses to global
      stimuli than a healthy comparison group (n = 29). They exhibited a marked
      decrement in N150 ERP amplitude, which correlated with speed of response to
      global stimuli. They also failed to show an augmented P300 response to local
      stimuli. CONCLUSIONS: Behavioral and physiological data are consistent and
      support a global visual processing deficit in schizophrenia. This is manifest at
      a relatively early stage of visual processing and might relate to physiological
      disturbances in areas V3/V3a of the extrastriate cortex.

PMID- 16084857
TI  - Monitoring the effects of chronic alcohol consumption and abstinence on brain
      metabolism: a longitudinal proton magnetic resonance spectroscopy study.
AB  - BACKGROUND: This study focused on metabolic brain alterations in recently
      detoxified alcohol-dependent patients (S1) and their possible reversibility after
      3 (S2) and 6 months (S3) of abstinence. METHODS: Thirty-three alcohol-dependent
      patients and 30 healthy control subjects were studied with multislice proton
      magnetic resonance spectroscopic imaging (echo time = 135 msec at 1.5 T at three
      time points). RESULTS: In the patient group, we found that choline-containing
      compounds (Ch) in three frontal and cerebellar subregions at S1 were
      significantly below normal, whereas N-acetyl aspartate (NAA) differences did not
      reach significance but showed a trend toward below-normal values in frontal white
      matter. Abstinent patients showed a significant increase of Ch in all subregions
      at S2. At S3, no further significant metabolite changes in abstinent patients
      compared with S2 could be detected. No significant increase of NAA could be
      detected at follow-up. CONCLUSIONS: The increase of the Ch signal in the follow
      up measurement after 3 months in abstinent alcohol-dependent patients supports
      the hypotheses of an alcohol- or alcohol detoxification-induced altered cerebral
      metabolism of lipids in membranes or myelin, which seems to be reversible with
      duration of alcohol abstinence.

PMID- 16084858
TI  - Functional neuroanatomy of body shape perception in healthy and eating-disordered
      women.
AB  - BACKGROUND: Abnormalities in perception and evaluation of body shape are a
      hallmark of eating disorders. METHODS: Brain responses to line drawings of
      underweight, normal weight, and overweight female bodies were measured with
      functional magnetic resonance imaging in 9 women with bulimia nervosa, 13 with
      anorexia nervosa, and 18 healthy women. Participants rated the stimuli for fear
      and disgust. RESULTS: In the three groups, the lateral fusiform gyrus, inferior
      parietal cortex, and lateral prefrontal cortex were activated in response to body
      shapes compared with the control condition (drawings of houses). The responses in
      the lateral fusiform gyrus and in the parietal cortex were less strong in
      patients with eating disorders compared with healthy control subjects. Patients
      with eating disorders rated the body shapes in all weight categories as more
      aversive than did healthy women. In the group with eating disorders, the aversion
      ratings correlated positively with activity in the right medial apical prefrontal
      cortex. CONCLUSIONS: Processing of female body shapes engages a distributed
      neural network, parts of which are underactive in women with eating disorders.
      The considerable variability in subjective emotional reaction to body shapes in
      patients with eating disorders is associated with differential activity in the
      prefrontal cortex.

PMID- 16084859
TI  - Heterogeneity of irritability in attention-deficit/hyperactivity disorder
      subjects with and without mood disorders.
AB  - BACKGROUND: We hypothesized that irritability is a heterogeneous symptom
      distinguished by severity and that attending to this heterogeneity would impact
      the relationship between irritability and bipolar disorder. METHODS: A total of
      274 ADHD children were administered the Kiddie Schedule for Affective Disorders
      and Schizophrenia (Epidemiologic Version) structured diagnostic interview. Three
      measures of irritability were identified: oppositional defiant disorder (ODD)
      type irritability, mad/cranky irritability, and super-angry/grouchy/cranky
      irritability. Subjects were stratified as having bipolar disorder (n = 30),
      unipolar depression (n = 100), and no history of depression or bipolar disorder
      (non-mood-disordered, n = 144). RESULTS: Oppositional defiant disorder-type
      irritability was very common in all ADHD subjects, was the least impairing, and
      did not increase the risk of mood disorder. Mad/cranky irritability was common in
      only ADHD children with a mood disorder, was more impairing than the ODD-type
      irritability, and was predictive of unipolar depression. Super
      angry/grouchy/cranky irritability was common only in ADHD children with bipolar
      disorder, was the most impairing, and was predictive of both unipolar depression
      and bipolar disorder. Two percent of the subjects with ODD-type irritability
      only, 6% of subjects with mad/cranky irritability, and 46% of subjects with super
      angry/grouchy/cranky irritability were diagnosed with bipolar disorder.
      CONCLUSIONS: These results challenge the conclusion that irritability is
      necessarily a poor diagnostic indicator of bipolar disorder in children.

PMID- 16084860
TI  - Reduced anterior cingulate glutamate in pediatric major depression: a magnetic
      resonance spectroscopy study.
AB  - BACKGROUND: Anterior cingulate cortex has been implicated in the pathogenesis of
      major depressive disorder (MDD). With single voxel proton magnetic resonance
      spectroscopy, we reported reductions in anterior cingulate glutamatergic
      concentrations (grouped value of glutamate and glutamine) in 14 pediatric MDD
      patients versus 14 case-matched healthy control subjects. These changes might
      reflect a change in glutamate, glutamine, or their combination. METHODS: Fitting
      to individually quantify anterior cingulate glutamate and glutamine was performed
      in these subjects with a new basis set created from data acquired on a 1.5 Tesla
      General Electric Signa (GE Healthcare, Waukesha, Wisconsin) magnetic resonance
      imaging scanner with LCModel (Version 6.1-0; Max-Planck-Institute, Gottingen,
      Germany). RESULTS: Reduced anterior cingulate glutamate was observed in MDD
      patients versus control subjects (8.79 +/- 1.68 vs. 11.46 +/- 1.55, respectively,
      p = .0002; 23% decrease). Anterior cingulate glutamine did not differ
      significantly between patients with MDD and control subjects. CONCLUSIONS: These
      findings provide confirmatory evidence of anterior cingulate glutamate
      alterations in pediatric MDD.

PMID- 16084861
TI  - Novel concepts of human chorionic gonadotropin: reproductive system interactions
      and potential in the management of infertility.
AB  - OBJECTIVE: To extensively review the scientific literature on the potential sites
      of hCG action and the role of this hormone on reproductive processes not
      necessarily related to the classic hCG functions of supporting early pregnancy.
      DESIGN: Review of the international scientific literature and the authors'
      personal research experience in this area. RESULT(S): The LH/hCG receptor has an
      almost ubiquitous distribution in reproductive organs, thus suggesting that the
      actions of hCG might be more extensive than previously thought. Independently of
      FSH, low-dose hCG can support development and maturation of larger ovarian
      follicles that have acquired granulosa cells LH/hCG receptors, potentially
      providing effective and safer ovulation induction regimens. Human chorionic
      gonadotropin seems to be capable of improving uterine receptivity by enhancing
      endometrial quality and stromal fibroblast function. Furthermore, through its
      actions on insulin-like growth factor binding protein-1 and vascular endothelial
      growth factor, hCG might stimulate endometrial angiogenesis and growth and extend
      the implantation window, thus making pregnancy more likely. CONCLUSION(S):
      Mounting evidence indicates that hCG could be mediating relevant actions
      enhancing fertility and the efficacy of therapeutic procedures used in the
      management of infertility. Greater understanding of the physiologic roles that
      hCG plays in human reproduction might suggest novel clinical applications for
      this traditional hormone of pregnancy.

PMID- 16084862
TI  - Long-term effects of hormone therapy on skin rigidity and wrinkles.
AB  - OBJECTIVE: To evaluate the effects of long-term hormone therapy (HT) on skin
      rigidity and wrinkling. DESIGN: Single blinded cross-sectional analysis. SETTING:
      Academic medical center. PATIENT(S): Sixty-five long-term HT users who underwent
      menopause at least 5 years before evaluation and who have either consistently
      used HT or have never used HT. INTERVENTION(S): Visual assessment of severity of
      wrinkles at 11 facial locations using the Lemperle scale by a plastic surgeon
      blinded to HT use. Measurement of skin rigidity at the cheek and forehead with a
      durometer. MAIN OUTCOME MEASURE(S): Lemperle wrinkle score and skin rigidity.
      RESULT(S): Twenty women met inclusion criteria. Eleven women who had not used HT
      were compared to nine long-term HT users. Demographics including age, race, sun
      exposure, sunscreen use, tobacco use, and skin type were similar. Rigidity was
      significantly decreased in HT users compared to nonusers at both the cheek (1.1
      vs. 2.7) and forehead (20 vs. 29). Average wrinkle scores were lower in hormone
      users than in nonhormone users (1.5 vs. 2.2). CONCLUSION(S): Long-term
      postmenopausal HT users have more elastic skin and less severe wrinkling than
      women who never used HT, suggesting that hormone therapy may have cosmetic
      benefits.

PMID- 16084863
TI  - A dermatologist's opinion on hormone therapy and skin aging.
AB  - The Taylor et al. study in this issue suggests that long-term hormone replacement
      therapy helps prevent skin aging. All patients interested in preventing skin
      aging should regularly use sunscreens, retinoids, and oral or topical
      antioxidants.

PMID- 16084864
TI  - Topical and oral estrogens revisited for antiaging purposes.
AB  - Topical and oral estrogens are beneficial in maintaining skin firmness and
      elasticity in postmenopausal women. The positive cutaneous effects of estrogen
      were overlooked in the Women's Health Initiative trial.

PMID- 16084865
TI  - Prevention during the menopause is critical for good health: skin studies support
      protracted hormone therapy.
AB  - Estrogen replacement therapy maintains the skin. Similar effects must be
      investigated in other organ systems.

PMID- 16084867
TI  - Failure of the emergency contraceptive levonorgestrel and the risk of adverse
      effects in pregnancy and on fetal development: an observational cohort study.
AB  - OBJECTIVE: To determine pregnancy and neonatal outcome after the failure of
      levonorgestrel as an emergency contraceptive. DESIGN: A retrospective
      observational cohort study. SETTING: Telephone consultations concerning
      reproductive risk factors conducted by Telefono Rosso-Teratology Information
      Service, Catholic University of Sacred Heart, Rome, Italy. PATIENT(S): Women
      exposed to levonorgestrel (36 cases) compared with a control group (80 cases).
      INTERVENTION(S): Teratological counseling. MAIN OUTCOME MEASURE(S): The rate of
      congenital anomalies, the prepartum or peripartum complications, and the
      pregnancy outcomes. RESULT(S): Twenty-five exposed newborns with length and
      weight identical to that of the control group were shown to be without increased
      risk of congenital malformation. No statistical differences were observed in
      terms of spontaneous or legal abortion and pregnancy and neonatal complications,
      and there was no ectopic pregnancy in either group. CONCLUSION(S): Although the
      sample size was small, in our experience, the failure of levonorgestrel as an
      emergency contraceptive was not associated with an increased risk of major
      congenital malformations, prepartum or peripartum complications, or an adverse
      pregnancy outcome.

PMID- 16084868
TI  - Anastrazole and oral contraceptives: a novel treatment for endometriosis.
AB  - OBJECTIVE: To establish the use of aromatase inhibitors as a therapeutic option
      for endometriosis. DESIGN: Prospective open-label Food and Drug Administration
      phase 2 trial with Institutional Review Board approval. SETTING: Outpatient
      tertiary care centers. PATIENT(S): Fifteen premenopausal patients with documented
      refractory endometriosis and chronic pelvic pain. INTERVENTION(S): After a 1
      month washout of endometriosis hormone therapies, women took 1 mg anastrazole
      (Arimidex; AstraZeneca, Wilmington, DE) and one tablet of 20 microg ethinyl
      estradiol/0.1 mg levonorgestrel (Alesse; Wyeth, Madison, NJ) daily for 6 months.
      MAIN OUTCOME MEASURE(S): An analog pain scale recorded pelvic pain in daily
      diaries and surveys at baseline and after each treatment month. Side effects,
      blood counts, liver and renal function tests, cholesterol levels, and bone
      density were monitored. RESULT(S): Fourteen of 15 patients achieved significant
      pain reduction. Median pain scores decreased 55% after 6 months, while mean pain
      scores decreased 40%. Pain reduction comparing each treatment month to baseline
      achieved statistical significance. Average pain scores began dropping after only
      1 treatment month and continued decreasing each additional month. No organ system
      experienced adverse effects. Estradiol levels were suppressed during treatment.
      Side effects were mild and improved over time. CONCLUSION(S): Fourteen of 15
      patients with refractory endometriosis achieved significant pain relief using
      anastrazole and 20 microg ethinyl estradiol/0.1 mg levonorgestrel with minimal
      side effects. This treatment for endometriosis is a promising new modality that
      warrants further investigation.

PMID- 16084869
TI  - Increased dioxin-like compounds in the serum of women with peritoneal
      endometriosis and deep endometriotic (adenomyotic) nodules.
AB  - OBJECTIVE: To investigate the possible association between the body burden of
      dioxin-like compounds and endometriotic disease. DESIGN: Case-control study.
      SETTING: Gynecology ward in a university hospital. PATIENT(S): Seventy-one women
      with peritoneal endometriosis (n = 25) or deep endometriotic (adenomyotic)
      nodules (n = 25) and controls (n = 21). INTERVENTION(S): Collection of 200 mL of
      blood (fasted) and face-to-face interview. MAIN OUTCOME MEASURE(S): Assessment of
      dioxin (PCDD), furan (PCDF), and dioxin-like PCB serum concentrations (picograms
      toxic equivalent [TEQ]/g lipids). RESULT(S): Age and body mass index were traced
      by linear multiple regression as determinants of total TEQ levels. After
      standardization for these variables (30 years and 22.5 kg/m2), the mean TEQ
      levels were 24.21 (controls), 30.62 (peritoneal endometriosis), and 37.60 (deep
      endometriotic [adenomyotic] nodules) pg TEQ/g lipids. Logistic regression
      analysis indicated a significantly increased risk of deep endometriotic
      (adenomyotic) nodules (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.4
      7.6) for an increment of 10 pg in total TEQ levels/g lipids. An increased risk
      was also found for peritoneal endometriosis (OR, 1.9; 95% CI, 0.9-3.8) for total
      TEQ levels and for dioxins alone (OR, 3.2; 95% CI, 1.0-9.9). CONCLUSION(S): The
      results provide the first epidemiological evidence of an association between
      increased PCDD/PCDF and PCB body burden and endometriosis.

PMID- 16084870
TI  - Evaluating the role of exogenous luteinizing hormone in poor responders
      undergoing in vitro fertilization with gonadotropin-releasing hormone
      antagonists.
AB  - OBJECTIVE: To evaluate the importance of exogenous LH in poor responders
      undergoing IVF with GnRH antagonists. DESIGN: Retrospective cohort study.
      SETTING: University-based IVF center. PATIENT(S): All patients with a history of
      poor response to ovarian stimulation undergoing IVF with GnRH antagonists between
      September 2000 and August 2001. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Clinical pregnancy rates. RESULT(S): Two hundred forty GnRH-antagonist cycles
      were initiated in poor responders. One hundred fifty-three progressed to oocyte
      retrieval. Seventy-five patients received recombinant FSH (Rec) for ovarian
      stimulation, and 66 received hMG in combination with Rec. In patients aged <40
      years, there were no significant differences in amount and duration of treatment,
      number of oocytes retrieved, and number of embryos between treatment groups. In
      patients aged > or =40 years, significantly fewer oocytes were retrieved in
      groups who received exogenous LH in their stimulation, resulting in significantly
      fewer fertilized embryos. Implantation and clinical pregnancy rates did not
      differ by treatment group. CONCLUSION(S): In poor responders undergoing IVF with
      GnRH antagonists, outcomes are comparable whether stimulation is achieved in the
      presence or absence of supplemental LH. Exogenous LH does not appear to be
      necessary to achieve pregnancy in these challenging patients and may be
      detrimental to older patients with a history of poor response.

PMID- 16084871
TI  - Preimplantation genetic diagnosis for aneuploidy screening in women older than 37
      years.
AB  - OBJECTIVE: To provide background information about the average aneuploidy and
      implantation rates of older patients after IVF with preimplantation genetic
      diagnosis for aneuploidy screening (PGD-AS) when the patients are subdivided into
      age categories; and to compare pregnancy outcome data after PGD-AS in this group
      of patients with a similar control group. DESIGN: Retrospective clinical study.
      SETTING: Patients in an academic reproductive medicine unit. PATIENT(S): All
      patients 37 years or older who had PGD-AS between October 1999 and December 2003
      and all pregnant patients 37 years or older who had IVF/intracytoplasmic sperm
      injection without PGD-AS during the same period of time. INTERVENTION(S): IVF
      with PGD-AS. MAIN OUTCOME MEASURE(S): Aneuploidy rate, miscarriage rate, live
      birth rate, implantation rate, multiple pregnancy rate, and prenatal testing.
      RESULT(S): Three hundred ninety-four PGD-AS cycles of patients between 37 and 46
      years of age were analyzed. The aneuploidy rate gradually increased with age. The
      implantation rate remained similar over all age groups. There was a trend to a
      lower miscarriage and multiple pregnancy rate in the PGD-AS group and a higher
      delivery/live birth rate. There were five elective terminations of pregnancy
      after prenatal testing and three late miscarriages due to prenatal testing in the
      control group. CONCLUSION(S): Preimplantation genetic diagnosis for aneuploidy
      screening can give valuable information to older patients concerning the reason
      why their IVF cycles are unsuccessful and whether it is worthwhile to continue
      IVF treatment, and it can help patients to avoid the emotional trauma that can
      occur after prenatal testing during the second trimester of pregnancy.

PMID- 16084872
TI  - High rates of embryo wastage with use of assisted reproductive technology: a look
      at the trends between 1995 and 2001 in the United States.
AB  - OBJECTIVE: To determine what percentage of embryos achieved through assisted
      reproductive technology (ART) do not result in a live birth and to examine the
      relationships among the number of embryos transferred, infants delivered, and
      embryos wasted. DESIGN: Retrospective correlational study of the U.S. summary
      data of ART results for the years of 1995-2001. PATIENTS: Fertility clinics
      reporting data to the Society of Assisted Reproductive Technology (SART).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Statistics for ART cycles using
      fresh, nondonor eggs and embryos were derived, and the percentage of embryos
      wasted each year was calculated. Trends over time were evaluated for percent
      embryos wasted, the average number of embryos transferred, and the delivery per
      transfer rate. Correlations between these variables were analyzed. RESULT(S): The
      percentage of embryos transferred that did not produce a live birth was 90.8 in
      1995 and decreased to 84.9 in 2001. This trend significantly correlated with a
      reduction in the number of embryos transferred (from 3.9 to 3.1) and with an
      improvement in delivery rate per transfer (25% to 33.4%). CONCLUSION(S): The vast
      majority of embryos produced in vitro and transferred fail to develop into an
      infant, supporting the concept that only a small fraction of embryos has the
      capacity to become a live birth. Clinicians should strive to reduce embryonic
      wastage without an adverse effect on delivery rates by perfecting methods of
      ovarian stimulation and embryo screening, and by transferring fewer embryos.

PMID- 16084873
TI  - Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years
      and older with a history of recurrent miscarriages.
AB  - OBJECTIVE: To determine whether preimplantation genetic diagnosis (PGD) and
      transfer of euploid embryos would decrease spontaneous abortion rates in
      recurrent miscarriage (RM) patients. DESIGN: Controlled clinical study. SETTING:
      In vitro fertilization centers and PGD reference laboratory. PATIENT(S):
      Recurrent-miscarriage patients with three or more prior lost pregnancies with no
      known etiology. INTERVENTION(S): Biopsy of a single blastomere from each day 3
      embryo, followed by fluorescence in situ hybridization analysis. MAIN OUTCOME
      MEASURE(S): The rate of spontaneous abortions in RM subjects undergoing PGD were
      compared with [1] their own a priori expectations and [2] a comparison group of
      women undergoing PGD for advanced maternal age (> or =35 years). RESULT(S):
      Before PGD, RM patients had lost 87% (262/301) of their pregnancies, with an
      expected loss rate of 36.5%. After, they only lost 16.7% pregnancies. This
      difference was mostly due to reduction in pregnancy loss in the > or =35-years
      age subgroup, to 12% from an expected 44.5%. CONCLUSION(S): Preimplantation
      genetic diagnosis aneuploidy screening has a beneficial effect on pregnancy
      outcome in RM couples, especially those in which the woman is aged > or =35
      years. Our data indicate that PGD reduces the risk of miscarriage in RM patients
      to baseline levels.

PMID- 16084874
TI  - Diploid-aneuploid mosaicism in human embryos cultured to the blastocyst stage.
AB  - OBJECTIVE: To examine diploid-aneuploid mosaicism in human in vitro cultured
      blastocysts. DESIGN: A laboratory study on spare blastocysts from an IVF program.
      SETTING: University hospital laboratory. PATIENTS(S): Forty-three couples
      undergoing IVF or intracytoplasmic sperm injection. INTERVENTION(S): Ninety-one
      blastocysts were spread for fluorescence in situ hybridization using the HCl
      Tween 20 method. A total of 6,664 nuclei were analyzed for aneuploidy using
      fluorescent DNA probes specific to chromosomes 2, 7, and 18. MAIN OUTCOME
      MEASURE(S): The proportion of aneuploid cells within each blastocyst. RESULTS(S):
      The incidence of diploid-aneuploid mosaicism among 91 blastocysts examined was
      17.6%. All of the mosaic blastocysts were abnormal for only one of the three
      chromosomes tested, with the incidence of involvement of chromosomes 2, 7, and 18
      being 3.3%, 8.8%, and 5.5%, respectively. The majority of the mosaic blastocysts
      had low proportions of aneuploid cells. Ten of the 16 (62.5%) affected
      blastocysts were of morphology compatible with implantation. CONCLUSION(S): A
      considerable proportion of human IVF blastocysts show a form of mosaicism that
      has been observed in fetal and placental tissues. This mosaicism often arises at
      the final stage of preimplantation development in vitro and is present in
      blastocysts of morphology compatible with implantation.

PMID- 16084875
TI  - Association of abnormal morphology and altered gene expression in human
      preimplantation embryos.
AB  - OBJECTIVE: We set out to characterize the expression of nine genes in human
      preimplantation embryos and determine whether abnormal morphology is associated
      with altered gene activity. DESIGN: Reverse transcription and real-time
      polymerase chain reaction were used to quantify the expression of multiple genes
      in each embryo. The genes studied have various important cellular roles (e.g.,
      cell cycle regulation, DNA repair, and apoptosis). SETTING: Research laboratory
      working closely with a clinical IVF practice. PATIENT(S): Over 50 embryos were
      donated by infertile patients (various etiologies). Among these, all major stages
      of preimplantation development and a variety of common morphologic abnormalities
      were represented. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quantification
      of mRNA transcripts. RESULT(S): We detected an association between certain forms
      of abnormal morphology and disturbances of gene activity. Cellular fragmentation
      was associated with altered expression of several genes, including TP53,
      suggesting that fragmenting blastomeres are suffering stress of a type monitored
      by p53, possibly as a consequence of suboptimal culture conditions.
      CONCLUSION(S): Appropriate gene expression is vital for the regulation of
      metabolic pathways and key developmental events. Our data indicates a possible
      causal relationship between changes in gene expression and the formation of
      clinically relevant abnormal embryo morphologies. We hypothesize that embryos
      with expression profiles characteristic of good morphology and appropriate for
      their developmental stage have the greatest potential for implantation. If
      confirmed, this could lead to a new generation of preimplantation genetic
      diagnosis (PGD) tests for assessing embryo viability and predicting implantation
      potential.

PMID- 16084876
TI  - Redefining the relationship between sperm deoxyribonucleic acid fragmentation as
      measured by the sperm chromatin structure assay and outcomes of assisted
      reproductive techniques.
AB  - OBJECTIVE: To test the hypothesis that couples with sperm chromatin structure
      assay (SCSA) DNA fragmentation index (DFI) values >27% would not achieve
      pregnancy with assisted reproductive techniques (ART) and to investigate how DFI
      and high DNA stainability (HDS), as measured by the SCSA, affect fertilization,
      cleavage, implantation, and pregnancy rates in IVF cycles. DESIGN: Prospective
      clinical study. SETTING: Academic human reproduction laboratory. PATIENT(S): One
      hundred couples undergoing IVF with conventional insemination or intracytoplasmic
      sperm injection. INTERVENTION(S): Testing with SCSA was performed by SCSA
      Diagnostics (Brookings, South Dakota) on a semen aliquot taken from ejaculate
      used for ART. MAIN OUTCOME MEASURE(S): Relating total DFI and HDS to conventional
      semen parameters and cycle-specific outcomes after ART. RESULT(S): Nine of
      nineteen couples achieved clinical pregnancy when DFI was > or =27%, and 2 of 22
      couples achieved clinical pregnancy when DFI was < or =9%. One of nine couples
      achieved clinical pregnancy with HDS >17%. The DFI was negatively correlated with
      sperm density (r = -0.23, P<.03) and motility (r = -0.55, P<.00), and HDS was
      negatively correlated with sperm density (r = -0.37, P<.00). CONCLUSION(S): Sperm
      chromatin structure assay failed to identify elevated DFI thresholds for negative
      pregnancy outcome after ART. Patients with low DFI (< or =9%) were least likely
      to become pregnant, which is also contradictory to SCSA marketing, which states
      that DFIs of < or =15% have excellent fertility potential. Patients with HDS > or
      =17% had low pregnancy rates, indicating decreased fertility potential, which
      deserves further investigation. Larger studies are necessary to confirm that low
      DFI is associated with decreased fertility and, if proved, might redefine the use
      of the SCSA in evaluating infertility.

PMID- 16084877
TI  - Fluorescence in situ hybridization sperm analysis of six translocation carriers
      provides evidence of an interchromosomal effect.
AB  - OBJECTIVE: To investigate the existence of an interchromosomal effect in balanced
      reciprocal translocation carriers and to evaluate their risk of having an
      affected child or repeated spontaneous abortions. DESIGN: Analysis of chromosomal
      sperm content by fluorescence in situ hybridization (FISH) using probes for
      chromosomes 1, 15, 16, 17, 18, X, and Y. SETTING: University hospital.
      PATIENT(S): Six male carriers of balanced chromosome rearrangements, one with
      normal sperm parameters and five with oligoasthenoteratozoospermia, and seven
      fertile controls. INTERVENTION(S): Fluorescence in situ hybridization for
      chromosomal enumeration on sperm samples. MAIN OUTCOME MEASURE(S): Rate of disomy
      for the studied chromosomes. RESULT(S): A total of 123,842 spermatozoa were
      scored (82,181 for controls and 41,661 for patients). For each patient, at least
      one chromosome studied presented a significantly increased rate of disomy. One
      patient showed a clear interchromosomal effect for at least three of the six
      chromosomes studied. Disomy rates were statistically significantly and inversely
      correlated with the total progressive motility of spermatozoa. CONCLUSION(S): The
      observed interchromosomal effect seems to be translocation, patient, and
      chromosome dependent. Variable effects were observed, according to the chromosome
      studied. When we looked at patients carrying the same translocation, the level of
      disomy rate was variable and affected different chromosomes.

PMID- 16084878
TI  - Prior oral contraception and postmenopausal fracture: a Women's Health Initiative
      observational cohort study.
AB  - OBJECTIVE: To test for the possible association of past oral contraceptive (OC)
      use and incident fracture after menopause. DESIGN: A prospective cohort of 93,725
      postmenopausal women. SETTING: Forty Women's Health Initiative (WHI) clinical
      centers across the United States. PATIENT(S): Ethnically diverse 93,725 volunteer
      postmenopausal women, 50 to 79 years old. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): The main outcome was self-reported incident first fracture assessed
      prospectively by annual questionnaire. RESULT(S): The adjusted relative hazard
      (HR) for fracture among past OC users was 1.07 (95% CI, 1.01-1.15). Among women
      without any postmenopausal hormone treatment, past OC use for < or =5 years led
      to an HR of 1.15 (95% CI, 1.04-1.27) and for past OC use >5 years led to an HR of
      1.09 (95% CI, 0.97-1.23) compared with never users. CONCLUSION(S): This study
      does not support the idea that past OC use protects against later fracture.

PMID- 16084879
TI  - Effect of different preparations of hormone therapy on lipid and glucose
      metabolism, coagulation factors, and bone mineral density in overweight and obese
      postmenopausal women.
AB  - OBJECTIVE: To determine the effects of different preparations of hormone therapy
      (HT) on lipid and glucose metabolism, coagulation factors, and bone mineral
      density (BMD) in overweight and obese postmenopausal women. DESIGN: A randomized,
      nonblinded, controlled study. SETTING: Karadeniz Technical University, Department
      of Obstetrics and Gynecology. PATIENT(S): A total of 352 overweight and obese
      (body mass index >25 kg/m2) postmenopausal women. INTERVENTION(S): Ninety women
      received 2.5 mg of tibolone; 84 received 2 mg of E2 plus 1 mg of norethisterone
      acetate (E2/NETA); 90 received 0.625 mg of conjugated equine estrogen plus 2.5 mg
      of medroxyprogesterone acetate (CEE/MPA); and 88 did not receive any menopausal
      therapy (control). MAIN OUTCOME MEASURE(S): At baseline and after 6 months of
      treatment, we measured total cholesterol, triglyceride, high-density lipoprotein
      cholesterol (HDL), low-density lipoprotein cholesterol (LDL), insulin, glucose,
      factor VII, factor VIII, von Willebrand factor, antithrombin III, protein S,
      protein C, fibrinogen, and BMD at the lumbar spine L1-L4. RESULT(S): There were
      no statistically significant differences among the groups for any variables at
      baseline. After 6 months of treatment, the three regimens decreased total
      cholesterol, triglyceride, LDL, and fibrinogen; E2/NETA and CEE/MPA increased
      HDL, and tibolone decreased HDL; higher insulin concentrations were found in the
      control and tibolone groups. Body mass index, HDL, fibrinogen levels, and L1-L4
      BMD were independent factors in the prediction of HT use. CONCLUSION(S): Body
      mass index, HDL, fibrinogen levels and L1-L4 BMD were independent factors in the
      prediction of HT use. Treatment with tibolone, E2/NETA, and CEE/MPA resulted in
      minimal improvement in lumbar spine BMD but had a beneficial effect on the
      procoagulation system, with minimal changes in glucose metabolism after 6 months
      of therapy.

PMID- 16084880
TI  - Efficacy of low-dose human chorionic gonadotropin alone to complete controlled
      ovarian stimulation.
AB  - OBJECTIVE: To prove that low-dose hCG alone can be clinically used to replace FSH
      containing gonadotropins to complete controlled ovarian hyperstimulation (COH).
      DESIGN: Controlled, prospective, randomized study. SETTING: Academic center.
      PATIENT(S): Infertile patients who are candidates for assisted reproduction.
      INTERVENTION(S): Patients received [1] recombinant FSH or hMG throughout COH
      (group A); [2] ovarian priming with recombinant FSH/hMG followed by low-dose hCG
      (200 IU/day) alone (group B). MAIN OUTCOME MEASURE(S): Medication consumption;
      daily serum and follicular fluid (FF) measurements of LH, FSH, hCG, E2, P, T, and
      androstenedione (A); number and size of follicles; intracytoplasmic sperm
      injection (ICSI) outcome. RESULT(S): In group B: [1] duration and dose of
      recombinant FSH/hMG administration were reduced; [2] preovulatory serum hCG, E2,
      and T were higher, whereas FSH was lower; [3] FF hCG, E2, T levels, and E2/T,
      E2/A, and E2/P ratios were higher, whereas A was lower; [4] small but not large
      preovulatory follicles were reduced; [5] fertilization rates were higher; and [6]
      serum and FF P levels, and ICSI outcome did not differ. CONCLUSION(S): Low-dose
      hCG alone in the late COH stages: [1] reduced recombinant FSH/hMG consumption
      whereas ICSI outcome was comparable to traditional COH regimens; [2] stimulated
      follicle growth and maturation independent of FSH administration; [3] was
      associated with a reduced number of small preovulatory follicles; [4] did not
      cause premature luteinization; [5] resulted in a more estrogenic intrafollicular
      environment.

PMID- 16084881
TI  - Comparison of a gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist
      flare-up regimen in poor responders undergoing ovarian stimulation.
AB  - OBJECTIVE: To compare the efficacy of flare-up and GnRH-antagonist treatment in
      poor-responder patients. DESIGN: Randomized prospective study. SETTING: Assisted
      reproduction center. PATIENT(S): Fifty-five poor-responder patients undergoing
      intracytoplasmic sperm injection (ICSI). INTERVENTION(S): Thirty patients
      received GnRH agonist on the 1st day of menstruation, followed by exogenous
      gonadotropins from the 2nd day. Twenty-five patients received exogenous
      gonadotropins starting on the second day of menstruation, followed by GnRH
      antagonist when the leading follicle reached 14 mm in diameter. MAIN OUTCOME
      MEASURE(S): The total dose of FSH administered during the ovarian stimulation, as
      well as the number of mature oocytes retrieved, embryo quality, fertilization,
      implantation, and pregnancy rates were evaluated. RESULT(S): The number of
      ampules and units of FSH administered were significantly less in the flare-up
      than in the antagonistic group. The numbers of mature oocytes retrieved and of
      top-quality embryos transferred were significantly greater in the flare-up than
      in the GnRH-antagonist group. The fertilization rate (84% vs. 63%) was
      significantly higher in the flare-up than in the GnRH-antagonist group. The
      implantation and pregnancy rate were similar in the two groups. CONCLUSION(S):
      The flare-up protocol appears to be more effective than the GnRH-antagonist
      protocol in terms of mature oocytes retrieved, fertilization rate, and top
      quality embryos transferred in poor-responder patients.

PMID- 16084882
TI  - Association of Gly972Arg variant of insulin receptor substrate-1 with metabolic
      features in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To examine the prevalence and the effects of Gly972Arg (G972A) variant
      of insulin receptor substrate-1 (IRS-1) in women with polycystic ovary syndrome
      (PCOS). DESIGN: Controlled clinical study. SETTING: An academic clinical research
      center. PATIENT(S): Sixty women with PCOS and 60 control women matched for age.
      INTERVENTION(S): Biometric measures, metabolic and hormonal measures, genetic
      analyses. MAIN OUTCOME MEASURE(S): Serum androgens, glucose, and insulin were
      measured. Blood leukocytes were used for genetic analyses. RESULT(S): The G972A
      variant was encountered more often in women with PCOS. The G972A carriers were
      more obese than their counterparts, had higher fasting insulin levels, and were
      more insulin-resistant. However, androgen levels did not differ on the basis of
      IRS-1 genotype. CONCLUSION(S): We observed that the G972A variant of IRS-1 was
      more prevalent in women with PCOS, and that it had important metabolic effects
      without having a direct effect on the androgen levels. However, the G972A variant
      of IRS-1 may modulate reproduction by lowering sex hormone-binding globulin in
      both healthy women and women with PCOS.

PMID- 16084883
TI  - Ovarian size and blood flow in women with polycystic ovary syndrome and their
      correlations with endocrine parameters.
AB  - OBJECTIVE: To determine how common polycystic ovarian morphology may be in women
      given the clinical diagnosis of polycystic ovary syndrome (PCOS) based on chronic
      anovulation and hyperandrogenism and whether certain hormonal factors correlate
      with ovarian morphology and blood flow. DESIGN: Prospective study. SETTING: Two
      academic endocrinology centers in Italy. PATIENT(S): Three hundred twenty-six
      women with PCOS and 50 age-matched and weight-matched ovulatory women.
      INTERVENTION(S): Ultrasound assessment of ovarian morphology in patients and
      controls and ovarian blood flow and fasting hormone levels in a subset of 50
      patients and matched controls. MAIN OUTCOME MEASURE(S): Ovarian morphological
      assessments, ovarian blood flow by pulsatility index (PI) and resistance index
      (RI), and measurements of gonadotropins, estrogen, sex hormone-binding globulin,
      androgens, inhibin B, glucose, and insulin. RESULT(S): Using strict ultrasound
      criteria, 195 woman (60%) had enlarged ovaries, 135 (35%) had normal ovarian size
      but characteristic morphology, and 16 (5%) had normal size and morphology.
      Ovarian blood flow was increased (reduced PI and RI) in PCOS. All hormonal
      parameters were elevated in PCOS. Ovarian size correlated only with insulin and a
      measure of insulin resistance. Ovarian blood flow correlated positively with
      insulin, T, free T, and E2 but not with luteinizing hormone. Inhibin B showed a
      negative correlation with ovarian blood flow. CONCLUSION(S): When a clinical
      diagnosis of PCOS was made, virtually all women were found to have characteristic
      ovarian morphology. Insulin correlated with increased ovarian size as well as
      with increased blood flow. Blood flow also correlated positively with sex
      steroids but negatively with inhibin B.

PMID- 16084884
TI  - Treatment preferences and trade-offs for ovulation induction in clomiphene
      citrate-resistant patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate patient preferences and trade-offs for laparoscopic
      electrocautery of the ovaries relative to ovulation induction with recombinant
      FSH (rFSH) in patients with clomiphene citrate (CC)-resistant polycystic ovary
      syndrome (PCOS). DESIGN: Assessment of preferences and trade-offs in a randomized
      controlled trial. SETTING: Academic hospital. PATIENT(S): Thirty-two CC-resistant
      patients with PCOS who had been randomly assigned to either laparoscopic
      electrocautery of the ovaries or ovulation induction with rFSH and 32 control
      patients with PCOS under treatment with CC. INTERVENTION(S): Preference for
      laparoscopic electrocautery relative to rFSH was established during an interview.
      Trade-offs between treatment burden and effectiveness were evaluated by varying
      hypothetical pregnancy rates after laparoscopic electrocautery until patients
      switched in their initial preference. MAIN OUTCOME MEASURE(S): Preference for
      laparoscopic electrocautery of the ovaries; trade-off between burden and
      effectiveness of treatment. RESULT(S): The majority of the patients would prefer
      electrocautery of the ovaries over ovulation induction with rFSH if both
      treatment strategies resulted in similar pregnancy rates. However, most patients
      were willing to trade off their preference for increased effectiveness: the
      percentage of patients who preferred electrocautery over rFSH sharply declined
      when the difference in hypothetical pregnancy rates was more than 5% in favor of
      rFSH. CONCLUSION(S): Patients with polycystic ovary syndrome are well able to
      express an informed preference for laparoscopic electrocautery of the ovaries or
      ovulation induction with rFHS. Preferences are guided by features of the
      respective treatments but seem to be dominated by their effectiveness and safety.

PMID- 16084885
TI  - Assisted conception is a risk factor for postnatal mood disturbance and early
      parenting difficulties.
AB  - OBJECTIVE: To investigate whether assisted conception is associated with an
      increased risk of admission to a residential early parenting program for
      treatment of maternal mood disorder or infant feeding or sleeping disorders in
      the postpartum year. DESIGN: Systematic audit of consecutive medical records.
      SETTING: Masada Private Hospital Mother Baby Unit (MPHMBU), Melbourne, Australia.
      PATIENT(S): Medical records of all mother-infant dyads admitted to MPHMBU between
      July 2000 and August 2002. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Modes
      of conception and delivery of index infant, maternal and infant age on admission,
      multiplicity of birth, infant birth weight, and Edinburgh Postnatal Depression
      Scale scores. RESULT(S): A total of 745 records were audited, and mode of
      conception was recorded in 526 (70.6%) of records. Overall 6% (45/745) of the
      admitted infants had been conceived through assisted reproductive technologies
      compared with 1.52% in the general population (relative risk 4.0; 95% confidence
      interval, 3.0-5.4). Mothers who had conceived with assisted reproductive
      technologies were older and more likely to have had cesarean and multiple births
      than those who conceived spontaneously. CONCLUSIONS: Assisted conception appears
      to be associated with a significantly increased rate of early parenting
      difficulties. Women who experience assisted conception may require additional
      support before and after their babies are born.

PMID- 16084886
TI  - Parents' conceptualization of their frozen embryos complicates the disposition
      decision.
AB  - OBJECTIVE: To ascertain what couples think about their embryos and how they
      approach making a decision about disposition in light of the fact that the
      disposition of unused frozen embryos has significant implications for medical
      research and embryo donation. DESIGN: Ethnographic qualitative interview study.
      SETTING: Academic research environment. PATIENT(S): Fifty-eight couples who had
      conceived using a donor oocyte and had at least one frozen embryo in storage.
      MAIN OUTCOME MEASURE(S): Tape-recorded interviews with 58 wives and 37 husbands
      were transcribed and analyzed for emergent themes. RESULT(S): With an average of
      7.1 embryos per couple, after an average of 4.2 years of storage, 72% of couples
      with frozen embryos had not reached a disposition decision. Most couples had not
      anticipated or appreciated the consequences of having surplus embryos. Parents
      variously conceptualized frozen embryos as biologic tissue, living entities,
      "virtual" children having interests that must be considered and protected,
      siblings of their living children, genetic or psychological "insurance policies,"
      and symbolic reminders of their past infertility. CONCLUSION(S): The disposition
      decision is not only a significant and frequently unresolved issue for couples
      with stored frozen embryos, but their deeply personal conceptualizations of their
      embryos contributes to their ambivalence, uncertainty, and difficulty in reaching
      a decision.

PMID- 16084887
TI  - One last chance for pregnancy: a review of 2,705 in vitro fertilization cycles
      initiated in women age 40 years and above.
AB  - OBJECTIVE: To describe live birth rates and predictors of success in 1-year age
      increments for women > or =40 years when initiating assisted reproductive
      technologies (ART). DESIGN: Retrospective database analysis. SETTING: A large
      university-affiliated infertility center. PATIENT(S): One thousand two hundred
      sixty-three women undergoing 2,705 ART cycles at age 40 or above.
      INTERVENTION(S): Couples undergoing ART. MAIN OUTCOME MEASURE(S): Pregnancy and
      live birth rates per cycle start were determined based on 1-year increments in
      women aged > or =40. Predictors of success, including number of embryos
      transferred, number of fetal heartbeats, availability of embryos for
      cryopreservation, and cycle day 3 FSH levels, were analyzed. RESULT(S): The
      overall live birth rate per cycle start was 9.7%. Cumulative live birth rates in
      women ranged from 28.4% if starting ART at age 40 to 0 by age 46. The overall
      spontaneous abortion rate was 32.6% (range, 23.9%-66.7%). Higher pregnancy rates
      were predicted by the greater number of embryos available for transfer, by the
      availability of excess embryos for cryopreservation, and by the presence of two
      fetal heartbeats on ultrasound. The outcome of the first IVF cycle did not
      predict the outcome of subsequent cycles. CONCLUSION(S): Assisted reproductive
      technology has a reasonable chance for success (>5%) up until the end of the
      forty-third year. Twins on initial ultrasound, large numbers of embryos available
      for transfer, and the presence of excess embryos for cryopreservation predict
      higher live birth rates.

PMID- 16084888
TI  - Single-nucleotide polymorphisms in the promoter region influence the expression
      of the human follicle-stimulating hormone receptor.
AB  - OBJECTIVE: To characterize novel single-nucleotide polymorphisms (SNPs) in the
      human FSH receptor (FSHR) promoter region. DESIGN: Retrospective and basic
      research study. SETTING: University hospital. PATIENTS: Women (202 from Germany
      and 55 from Indonesia) with male or tubal factor infertility undergoing
      controlled ovarian stimulation for IVF treatment. INTERVENTIONS: None. MAIN
      OUTCOME MEASURE(S): Frequency, distribution, and correlation with clinical data
      of the SNPs. Dual luciferase assays and electrophoretic mobility shift assays
      (EMSA). RESULT(S): We identified two SNPs and three mutations in the promoter
      region of the human FSHR which could be allocated to positions -29, -37, -114, 
      123, and -138 upstream of the translational initiation codon. One SNP showed a
      high incidence (-29: 44%, n = 202), but no correlation with basal FSH serum
      levels or ovarian response with the SNP at position -29 was found. Luciferase
      reporter assays, using pGL3 vector constructs, showed that mutations at positions
      -37 and -138 lead to significantly higher promoter activity. EMSA indicate that
      putative binding sites for transcription factors are affected by the SNPs.
      CONCLUSIONS: The newly identified SNPs do not seem to influence clinical
      parameters substantially, but modulate expression of the FSHR via changes in
      transcription factor binding sites.

PMID- 16084889
TI  - Analysis of the AhR, ARNT, and AhRR gene polymorphisms: genetic contribution to
      endometriosis susceptibility and severity.
AB  - OBJECTIVE: To explore whether polymorphisms in AhR, ARNT, and AhRR contribute to
      endometriosis susceptibility and severity. DESIGN: Case control study. SETTING:
      Hospital. PATIENT(S): One hundred thirty-eight Japanese women with or without
      endometriosis, diagnosed endoscopically. INTERVENTION(S): Endoscopic laparoscopy,
      with blood samples for genotyping obtained before the laparoscopic examination
      for genomic DNA extraction from peripheral leukocytes. MAIN OUTCOME MEASURE(S):
      AhR, ARNT, and AhRR polymorphisms were genotyped using real-time polymerase chain
      reaction (PCR) analysis. Odds ratios and 95% confidence intervals were calculated
      for AhR, ARNT, and AhRR genotypes to evaluate the risk of endometriosis.
      Associations between these polymorphisms and stage of endometriosis were also
      examined. RESULT(S): The C/G + G/G genotypes at codon 185 of AhRR showed a
      statistically significant association with risk of endometriosis (adjusted odds
      ratio, 2.53; 95% confidence interval, 1.16-5.55). Furthermore, a statistically
      significant trend associated the C/G + G/G genotypes with the clinical stage of
      endometriosis. No statistically significant association was observed between AhR
      codon 554 or ARNT codon 189 polymorphisms and endometriosis. CONCLUSION(S): AhRR
      codon 185 polymorphism was associated with susceptibility to and severity of
      endometriosis in Japanese women.

PMID- 16084890
TI  - Effects of aromatase inhibitors on proliferation and apoptosis in eutopic
      endometrial cell cultures from patients with endometriosis.
AB  - OBJECTIVE: To study the effect of letrozole (Let) and anastrozole (Anas) on
      apoptosis and cell proliferation in epithelial endometrial cells (EEC) from
      patients with endometriosis (EDT). DESIGN: Prospective study. SETTING: Research
      institute and clinical fertility center. PATIENT(S): Eighteen women with
      untreated EDT. INTERVENTION(S): Biopsy specimens of eutopic endometrium were
      obtained from all subjects. Apoptosis and cell proliferation were examined in EEC
      after incubation with Let or Anas. MAIN OUTCOME MEASURE(S): Percentage of
      apoptotic cells (ApC) was evaluated by the acridine orange-ethidium bromide
      technique; cell proliferation was assessed by 3H-thymidine incorporation.
      RESULT(S): Treatment with Let 10 nM and Let 100 nM enhanced values of ApC in
      cultures from EDT patients. Epithelial endometrial cells treated with Anas 100 nM
      or Anas 500 nM showed a statistically significant induction on apoptosis levels.
      Cultures treated with Let 1 nM or Anas 50 nM did not show any significant
      differences in ApC levels compared with basal conditions. 3H-Thymidine uptake was
      down regulated by Let 10 nM and Let 100 nM. Similarly, Anas 100 nM and Anas 500
      nM showed a significantly lower degree of cell proliferation in EEC. Lower
      concentrations of Let and Anas did not induce any significant change in cell
      proliferation rates. CONCLUSION(S): Our results show that Let and Anas produced a
      significant and positive effect on apoptosis and cell proliferation on EEC from
      EDT patients. These findings support the further investigation of aromatase
      inhibitors as a treatment option in EDT.

PMID- 16084891
TI  - Strong expression of steroid sulfatase in human cumulus cells in patients with
      endometriosis.
AB  - OBJECTIVE: To investigate the localization and expression of steroid sulfatase
      (STS) in cumulus cells obtained from subjects with and without endometriosis.
      DESIGN: Case-control study. SETTING: In vitro fertilization program at the Showa
      University School of Medicine. PATIENT(S): Cumulus cells (142 samples) were
      obtained from 49 patients for whom IVF was indicated. Some of these samples were
      taken from cases complicated by endometriosis (35 samples), polycystic ovary
      syndrome (PCOS; 16 samples), or latent hyperprolactinemia (16 samples).
      INTERVENTION(S): Immunohistochemical staining for STS. Measurement of STS mRNA
      expression by real-time polymerase chain reaction (PCR). MAIN OUTCOME MEASURE(S):
      Expression of STS mRNA and localization of STS. RESULT(S): Steroid sulfatase was
      localized in the cytoplasm of the cumulus cells, and expression of STS mRNA was
      observed. The expression level of STS mRNA from patients with endometriosis was
      significantly higher (11.8-fold) than that of patients without endometriosis.
      CONCLUSION(S): These results suggest a local steroidal regulation mechanism in
      cumulus cells. Although the physiological role of STS in cumulus cells remains
      unclear, STS may be involved in the quality of eggs in patients with
      endometriosis.

PMID- 16084892
TI  - Protective effect of vascular endothelial growth factor on histologic changes in
      testicular ischemia-reperfusion injury.
AB  - OBJECTIVE: To evaluate the efficacy of vascular endothelial growth factor (VEGF)
      on long-term histologic damage in testicular ischemia-reperfusion injury. DESIGN:
      Controlled experimental study using rats. SETTING: University of Mersin School of
      Medicine, Mersin, Turkey. ANIMAL(S): Sixteen adult male Wistar rats.
      INTERVENTION(S): Five rats underwent 2 hours of testicular torsion. Six rats
      received VEGF injection into the testis before detorsion. Five rats underwent
      sham operation. MAIN OUTCOME MEASURE(S): Mean seminiferous tubular diameter
      (MSTD), germinal epithelial cell thickness (GECT), mean testicular biopsy score
      (MTBS), and apoptosis (caspase-3-positive cells). RESULT(S): Testicular torsion
      detorsion caused a significant decrease in MSTD, GECT, and MTBS and a significant
      increase in the mean value of caspase-3-positive cells in ipsilateral testes but
      not in the contralateral testes. The MSTD, GECT, and MTBS of the ipsilateral
      testes were significantly higher in the group treated with VEGF than in the
      torsion-detorsion group. The animals treated with VEGF had a significant decrease
      in the mean value of ipsilateral testicular caspase-3-positive cells compared
      with the torsion-detorsion group. CONCLUSION(S): Vascular endothelial growth
      factor might have a role in testicular damage caused by ischemia-reperfusion.
      Administering VEGF before reperfusion might have the potential to decrease the
      long-term histologic damage after testicular torsion.

PMID- 16084893
TI  - Expression profile of the tumorigenic factors associated with tumor size and sex
      steroid hormone status in uterine leiomyomata.
AB  - OBJECTIVE: To use tissue microarray in combination with dendrogram cluster
      analysis to characterize some potential tumorigenic factors in association with
      tumor size and sex steroid hormone status in uterine leiomyomata. DESIGN:
      Expression analysis of 21 selected potential tumorigenic factors in 60 patients
      with uterine leiomyomata. SETTING: University clinical research laboratory.
      PATIENT(S): Hysterectomy specimens from 60 patients with uterine leiomyomata of
      different ages and tumor sizes. INTERVENTION(S): Tissue cores from normal
      myometrium and leiomyomata were examined by immunohistochemistry. MAIN OUTCOME
      MEASURE(S): Semiquantitative immunointensity was scored and analyzed by net gain
      and loss between normal myometrium and leiomyomata and integrated into dendrogram
      cluster tree view. RESULT(S): We found that upregulation of estrogen and
      progesterone receptors was reverse associated with tumor size. Upregulation of
      some factors (HMGA2, sex steroid receptor cofactors, proteins in insulin pathway,
      and CD24) were identified in a group of patients in their later forties, were
      associated with large fibroids, and were weakly affected by the SSH status
      (illustrated by endometrial phases and menopause). Downregulation of tuberin and
      glucocorticoid receptor was mostly isolated in a second group of women at their
      late reproductive age. CONCLUSION(S): Analyses of the sex steroid hormone
      receptors and the nonsex steroid hormone factors in leiomyomata and the matched
      myometrium showed different expression patterns in different tumor sizes and
      patients' ages. A group of patients in their late forties with the larger
      leiomyomata contributes largely by upregulation of nonsex steroid hormone
      factors. Adenomyosis is a protective factor preventing large leiomyomata.

PMID- 16084894
TI  - Effect of 17 beta-estradiol, progesterone, synthetic progestins, tibolone, and
      tibolone metabolites on vascular endothelial growth factor mRNA in breast cancer
      cells.
AB  - OBJECTIVE: To determine the effect of 17beta-estradiol, progesterone,
      medroxyprogesterone acetate, levonorgestrel, norethindrone, tibolone, and
      tibolone metabolites on vascular endothelial growth factor (VEGF) isoforms 121
      and 165 mRNA in two breast cancer cell lines, MCF-7 (estrogen receptor rich) and
      T47-D (progesterone receptor rich), in vitro. DESIGN: Prospective basic research
      study. SETTING: Basic research laboratory. PATIENT(S): None. INTERVENTION(S): MCF
      7 and T47-D cells were cultured to 80% confluence in vitro. After 24 hours'
      incubation in serum-free media, 1.0, 0.1, and 0.01 microM of 17beta-estradiol,
      tibolone, 3alpha-hydroxytibolone and 3beta-hydroxytibolone were added to MCF-7
      cells. Progesterone, medroxyprogesterone acetate, levonorgestrel, norethindrone,
      and Delta4 tibolone at 1.0, 0.1, and 0.01 microM were added to T47-D cells. The
      cells plus steroids were incubated for a further 24 hours. MAIN OUTCOME
      MEASURE(S): Isolation and identification of VEGF isoforms 121 and 165 using
      semiquantitative polymerase chain reaction, gel electrophoresis, with cyclophilin
      as an internal control. RESULT(S): 17beta-estradiol, tibolone, 3alpha
      hydroxytibolone, and 3beta-hydroxytibolone had no effect on VEGF mRNA in MCF-7
      cells. Progesterone, medroxyprogesterone acetate, levonorgestrel, and
      norethindrone increased VEGF mRNA in T47-D cells. Delta4-Tibolone also increased
      VEGF mRNA but to a lesser extent than the progestogens. CONCLUSION(S): 17beta
      estradiol, tibolone, and tibolone hydroxy-metabolites had no effect on VEGF mRNA
      in MCF-7 cells. Progesterone and progestins increased VEGF mRNA in T47-D breast
      cancer cells, but Delta4-tibolone was less effective than progestogens on this
      angiogenic gene in the T-47 D cells. This differential effect may be related to
      breast cancer growth.

PMID- 16084895
TI  - Time course of pelvic endometriotic lesion revascularization in a nude mouse
      model.
AB  - OBJECTIVE: To assess the timing of endometrial lesion revascularization in a
      murine model. DESIGN: Prospective experimental study. SETTING: An academic
      research environment. ANIMAL(S): Twenty-six nude mice. INTERVENTION(S):
      Endometriosis was induced in mice by intraperitoneal deposition of human
      menstrual endometrium. Endometrial implants were recovered on days 1, 3, 5, 8,
      10, 15, and 21 after implantation. MAIN OUTCOME MEASURE(S): Sections from the
      endometrial implants were immunostained with species-specific antiplatelet
      endothelial cell adhesion molecule-1 (PECAM-1) antibodies and vessels of murine
      and human origin were counted. RESULT(S): Endothelial cells of human origin in
      the implant progressively disappeared between day 3 and day 10. Seventy-eight
      percent of the vessel sections were positive for human PECAM-1 on day 5, 40.1% on
      day 8, and only 14.1% on day 10. However, there was a marked increase in murine
      PECAM-1-expressing vessels in endometrial stroma between day 5 (1.4%) and day 8
      (68.0%), 10 (69.5%), and 15 (87.2%). CONCLUSION(S): Our study demonstrates that
      PECAM-1 is a reliable endothelial cell marker to evaluate the role of
      angiogenesis in the nude mouse model. It also indicates that revascularization of
      human endometrial implants occurs between 5 and 8 days after implantation and
      involves the disappearance of native graft vessels, coinciding with the invasion
      of the interface and then the stroma by murine vessels.

PMID- 16084896
TI  - Three dimensional/four dimensional ultrasound-guided embryo transfer using the
      maximal implantation potential point.
AB  - OBJECTIVE: To evaluate the use of maximal implantation potential (MIP) point in
      conjunction with a 3D/4D ultrasound in order to facilitate embryo transfers and
      potentially improve pregnancy rate. DESIGN: Retrospective, observational study.
      SETTING: IVF Center. PATIENT(S): Between October 1, 2002, and August 27, 2004,
      1,222 patients who underwent 3D/4D-ultrasound guided embryo transfers.
      INTERVENTION(S): Ultrasound-guided embryo transfer using a 3D/4D ultrasound
      machine and the MIP point. MAIN OUTCOME MEASURE(S): Procedure feasibility with
      improved visibility. RESULT(S): Embryo transfers were performed at the MIP point
      and the pregnancy rate was 36.66% (average patient age, 37.6 years). Physicians
      reported improved visualization and a greater accuracy in the placement of
      embryos within the uterine cavity. CONCLUSION(S): The MIP point can be
      immediately identified and individualized for each patient. Embryo transfers at
      the MIP were associated with good implantation and pregnancy rates.

PMID- 16084897
TI  - Confirmation of Essure microinsert tubal coil placement with conventional and
      volume-contrast imaging three-dimensional ultrasound.
AB  - OBJECTIVE: To determine the accuracy of ultrasound in the assessment of proximal
      fallopian tube positioning of the Essure microinsert coil 3 months after
      postprocedure. DESIGN: Prospective cohort study (Canadian Task Force
      classification II-2). SETTING: Reproductive-age women in a tertiary care
      hospital. PATIENT(S): Reproductive-age women presenting with a request for
      permanent contraception. INTERVENTION(S): Hysteroscopic sterilization with the
      Essure microinsert coil and conventional or volume-contrast three-dimensional
      (3D) ultrasound imaging 3 months after the procedure. MAIN OUTCOME MEASURE(S):
      Coil position on ultrasound. RESULT(S): Forty-eight of the 50 patients had
      successful placement of the Essure coils, and three patients required a second
      attempt on one tube. Conventional or volume-contrast (3D) ultrasound showed
      proper positioning of the coils within the proximal fallopian tube in 42 women
      (84%); five women (10%) required hysterosalpingogram to show appropriate
      positioning. Two patients (4%) required laparoscopic tubal sterilization, and one
      patient (2%) was lost to follow-up. CONCLUSION(S): Transvaginal ultrasound is an
      acceptable method of confirming proper placement of the Essure microinsert coil
      within the proximal fallopian tube 3 months after the procedure.

PMID- 16084898
TI  - Interleukin-2 receptor beta (IL-2R beta)-627*C homozygote but not IL-12R beta 1
      codon 378 or IL-18 105 polymorphism is associated with higher susceptibility to
      endometriosis.
AB  - Interleukin (IL)-2 R-627*C homozygote and C allele are related to higher
      susceptibility to endometriosis. Interleukin-12Rbeta1 codon 378 and IL-18 105
      gene polymorphisms are not correlated with endometriosis development.

PMID- 16084899
TI  - Optimizing incubation conditions for the preservation of sperm motility in
      processed semen samples.
AB  - To determine the optimal conditions to maintain sperm motility and viability for
      prolonged periods, semen specimens were processed and cultured in different
      temperature and conditions. We conclude that processing of semen and incubation
      of sperm in protein-supplemented N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic
      acid (HEPES) human tubal fluid medium at room temperature best preserved
      viability and motility of sperm.

PMID- 16084900
TI  - Miscarriage in India: a population-based study.
AB  - This study estimated birth order-specific miscarriage rates and characterized the
      influence of maternal age using the complete birth history of 90,303 ever-married
      women from the 1998-2000 Indian National Family Health Survey. Rates of
      miscarriage in India were low in association with early childbearing, whereas
      birth order as well as age substantially influenced miscarriage risk.

PMID- 16084901
TI  - Role of the AZFd locus in spermatogenesis.
AB  - To determine the prevalence of Y-chromosome microdeletions among infertile men
      and to correlate the clinical presentation of the men with specific deletions,
      microdeletion analysis in 53 infertile men (30 nonobstructive azoospermic, 23
      severely oligozoospermic patients), and 100 age-matched, fathered normospermic
      men who had fathered children was performed by the multiplex PCR with 18
      different Y-chromosome-specific STS primer sets, spanning the AZFa, AZFb, AZFd,
      and AZFc regions. Detection of the same locus deletion of the AZFd region in
      three cases indicated the possible importance of the genes located in this region
      in spermatogenesis.

PMID- 16084902
TI  - Epidemiologic aspects of postpartum pituitary hypofunction (Sheehan's syndrome).
AB  - Two hundred seventy-nine (3.20%) of the 8,730 parous females aged 20-39 years and
      124 (4.18%) of 2,970 parous females aged 40 years or older who were screened were
      suspected to have Sheehan's syndrome; 115 and 55 of these females in the two age
      groups were fully evaluated, and 98 and 51 of them, respectively, were proven to
      have Sheehan's syndrome. At these rates, the projected number of women with
      Sheehan's syndrome among a total population of parous females aged > or =20 years
      (12,32,827, as per census data) would be 38,691 in the Kashmir valley of the
      Indian subcontinent.

PMID- 16084903
TI  - Predictivity of uterine artery, arcuate artery, and intraovarian artery Doppler
      indices measured on the day of human chorionic gonadotropin injection on
      pregnancy outcomes.
AB  - The uterine, arcuate, and intraovarian blood flow measurements by transvaginal
      color doppler ultrasonography on the day of hCG injection in 46 women undergoing
      treatment by IVF at Aegean University Family Planning and Infertility Research
      and Treatment Center were evaluated. In the pregnant group, average uterine and
      arcuate arteries blood flow resistance values were lower than those in
      nonpregnant women.

PMID- 16084904
TI  - Vaginal azithromycin and misoprostol before surgical abortion.
AB  - Vaginally administered oral azithromycin tablets and specially formulated
      azithromycin and misoprostol vaginal pessaries achieved tissue levels
      significantly higher than those required to treat chlamydial infection.

PMID- 16084905
TI  - Long-term effects of cryopreservation on human spermatozoa.
AB  - We evaluated the long-term effects of cryopreservation on spermatozoa of men with
      testicular cancer, lymphoma, and benign conditions. No statistically significant
      decrease in semen parameters was noted. Duration of follow-up was up to 5 years
      and mean follow-up was 2 years.

PMID- 16084906
TI  - Serum luteinizing hormone levels are markedly increased and significantly
      correlated with Delta 4-androstenedione levels in lean women with polycystic
      ovary syndrome.
AB  - Lean women with polycystic ovary syndrome have markedly increased serum
      luteinizing hormone levels, which are significantly correlated with Delta(4)
      androstenedione levels but not directly linked to insulin resistance.

PMID- 16084908
TI  - The challenges of analyzing cost-effectiveness with a computer model.

PMID- 16084909
TI  - Hot clues to the etiology of Mayer-Rokitansky-Kuster-Hauser syndrome?

PMID- 16084911
TI  - Hot clues to the etiology of Mayer-Rokitansky-Kuster-Hauser syndrome?

PMID- 16084912
TI  - The diagnosis of premenarcheal endometriosis.

PMID- 16084914
TI  - Delays in sperm processing--impact?

PMID- 16084915
TI  - Local control of blood loss.

PMID- 16084918
TI  - Estrogen and progesterone do not activate Fos in AVPV or LHRH neurons in male
      rats.
AB  - In rodents, females but not males, in response to escalating levels of estrogen,
      express a luteinizing hormone (LH) surge that is prompted by a surge in
      luteinizing hormone-releasing hormone (LHRH). It cannot take place if estrogen
      sensitive afferents located in the anteroventral periventricular nucleus (AVPV)
      are either absent or disabled. Males appear to lack the ability to exhibit an LH
      surge, but it is unclear what level of the CNS contributes to this dimorphic
      response. This study was conducted to determine whether estrogen followed by
      progesterone treatment (E + P) of gonadectomized males evokes Fos activation in
      LHRH and AVPV neurons as it does in females. The results indicated that,
      consistent with the males' inability to express an LH surge in response to E + P
      treatment, LHRH and AVPV neurons in males failed to show increased Fos
      activation. Examination of neuron nuclear antigen (NeuN, a neuron-specific
      marker), estrogen receptor (ERalpha) and progesterone receptor (PR) neurons in
      AVPV neurons indicated that, while essentially all the neurons of the caudal AVPV
      in males and females are steroid responsive, the male possessed half the number
      of steroid responsive neurons within the caudal AVPV (where activation of Fos is
      maximal in females) compared to the female. Together, these data indicate that
      the male lacks a substantial population of steroid receptive AVPV neurons and is
      unable to respond to the presence of E and P and activate either AVPV or LHRH
      neurons.

PMID- 16084919
TI  - Effect of foot bathing on distal-proximal skin temperature gradient in elders.
AB  - Increased distal (foot)-proximal (abdominal) skin temperature gradient (DPG) has
      been associated with better sleep initiation. Warm foot bath can affect distal
      skin temperature to change DPG. However, the optimum water temperature and
      duration necessary to raise DPG has not been established. This study explored the
      effects of 1-h foot bathing at two water temperatures of 40 and 41 degrees C,
      respectively, on DPG in Taiwanese elders (n=6, ages 60-73 years). Each subject's
      feet and legs were immersed in a temperature-controlled water tub to 20 cm above
      the ankles for 60 min in each of two water temperatures. Oral, abdominal, and
      foot temperatures were taken during (at 10-min intervals), and after (at 1-min
      intervals) foot bathing. DPG was calculated by subtracting abdominal temperature
      from foot temperature. Results showed the value of DPG was significantly
      increased in the 10th min bathing at both water temperatures and maintained above
      0 degrees C. DPG gradually declined after bathing at both water temperatures. The
      value of DPG with 41 degrees C water was slightly higher than 40 degrees C. All
      subjects tolerated both bathing temperatures well for 1h. Both 40 and 41 degrees
      C foot bathing for 1h can increase the DPG and may be an effective way to affect
      whole body skin blood flow and trigger heat dissipation.

PMID- 16084920
TI  - Effectiveness of a discharge-planning pilot program for orthopedic patients in
      Taiwan.
AB  - The purpose of this pilot project was to establish a discharge-planning model and
      evaluate its effectiveness. Orthopedic patients who scored 7 or above on a high
      risk screening form were recruited for the project. Case managers served as
      discharge planners, and handled the following procedures: screening of patients,
      drawing up of the discharge plan, providing pre-discharge instructions,
      coordinating resources and services, and telephone follow-up. Results showed that
      discharge planning improved both the completion rate of pre-discharge
      instructions and patient satisfaction with discharge planning. It is suggested
      that, in future research, experimental studies could be used to examine the
      effectiveness of discharge planning. The study showed the importance of dedicated
      case managers for improving the effectiveness of discharge planning.

PMID- 16084921
TI  - Children's voices: qualitative data from the 'Barretstown studies'.
AB  - This paper describes the experiences of children (7-16 years) affected by life
      threatening illness, attending a therapeutic recreation programme. In total, 240
      children completed self-report questionnaires prior to the programme, with
      decreased response rates at follow-up. This paper focuses on children's responses
      to open-ended questions. The main findings showed that children's expectations
      focused on the activities and social interactions they were looking forward to,
      while some were concerned about being away from home. Also two-thirds felt that
      they had acquired personal and social functioning skills. These findings are
      discussed in relation to the value of qualitatively accessing children's views
      and experiences.

PMID- 16084922
TI  - Managing fear of falling: Taiwanese elders' perspective.
AB  - The purpose of this study is to explore the underlying theoretical framework of
      managing fear of falling (FOF) among elders. A grounded theory approach was used.
      A purposive sample of 25 community-dwelling elders who admitted FOF was
      interviewed. Theoretical sampling was used to saturate the emergent concepts.
      Analysis of audiotaped interview transcripts generated a managing FOF process.
      Managing FOF is a dynamic process with consequences that are impacted by the
      level and which strategies are used with satisfaction by the elderly and
      supported by family/significant others. The study findings suggest that
      understanding the process of managing FOF from the perspective of elders is a
      significant first step in assisting them to prevent from falling.

PMID- 16084923
TI  - Reasons for leaving nursing care and improvements needed for considering a
      return: a study among Swedish nursing personnel.
AB  - Based on two research projects in Sweden during the 1990s, the aim of this study
      was to identify former nursing personnel's main reasons for leaving nursing care,
      and to find out under what circumstances they would consider returning. Two open
      ended questions in a questionnaire were analysed. The results showed that
      different aspects of working conditions, mainly working schedule, management and
      status of profession were the dominating reasons both for leaving and considering
      a return. The findings indicate that interventions required for retaining
      personnel in nursing care need to be addressed both at the political and at the
      local level.

PMID- 16084924
TI  - Risky procedures by nurses in hospitals: problems and (contemplated) refusals of
      orders by physicians, and views of physicians and nurses.
AB  - Occurrence of problems with, refusals of orders and contemplated refusals of
      orders for risky procedures by nurses in Dutch hospitals and views on the safety
      of performance was studied using postal questionnaires (600 physicians and 3200
      nurses, response 60-71%). Of the respondents, 11-30% experienced problems with
      and (contemplated) refusals of orders for risky procedures in the previous 12
      months. Gynaecologists and internists most frequently mentioned problems
      concerning the practical performance of the procedure (44% and 30%,
      respectively). The reason for a problem or a contemplated refusal most frequently
      given by nurses was that they disagreed with the medication policy (34% and 35%,
      respectively). The reason for a refusal most frequently given by the
      gynaecologists, internists and nurses was that the nurses themselves were of the
      opinion that they did not have the necessary authorisation (95%, 67%, and 62%,
      respectively). With regard to certain procedures, the views of professionals are
      more strict than the current legal regulations.

PMID- 16084925
TI  - Can a facilitated programme promote effective multidisciplinary audit in
      secondary care teams? An exploratory trial.
AB  - This 24-month exploratory study evaluated whether a 6-month programme supported
      by a trained external facilitator was feasible, acceptable and led to the
      adoption of a multidisciplinary approach to audit by secondary care staff.
      Undertaken in five acute hospital sites in the East Midlands UK, 22
      multidisciplinary teams were randomised to either an intervention or control arm.
      Employing mixed methods, a range of outcomes, including collaborative behaviour,
      was measured. The intervention was feasible and acceptable to staff. Involvement
      in the facilitated programme had a positive impact on self-reported knowledge
      (P=0.000 post-intervention and at 4-months follow-up), skills (P=0.000 post
      intervention and P=0.02 at 4-months follow-up) and attitudes (P<0.01 post
      intervention), appeared to have some influence on improving self-reported (P<0.05
      post-intervention) and observed collaborative behaviour (P=0.01) and led to
      better quality audit resulting in measurable improvements to care. Improved
      collaborative behaviour may have resulted from an increase in assertive behaviour
      by nurses. Research to test approaches to support teams to work effectively
      together is currently hampered by a lack of suitable research instruments and
      needs addressing before main (phase 111) trials are undertaken.

PMID- 16084926
TI  - The disciplinary code for nurses and its contribution to the quality of nursing
      care in the Netherlands.
AB  - AIM: To obtain insight into the contribution of the disciplinary code for nurses
      to monitoring the quality of nursing care in the Netherlands. METHODS: Complaints
      dealt with in the period 1998-2001 were studied. Questionnaires were sent to 3200
      nurses (71%), all 388 members of the disciplinary boards (89%) and 43 lawyers
      (65%). RESULTS: There was an increase in the number of nurses who were accused
      (20 in 1998, 12 in 1999, 54 in 2000, and 56 in 2001) and also in the annual
      percentages of sanctions imposed (0% in 1998, 8% in 1999, 13% in 2000 and 16% in
      2001). The disciplinary code appears to be an important corrective instrument for
      serious professional misconduct.

PMID- 16084927
TI  - A critical review of the inter-relationship between skin vulnerability and
      urinary incontinence and related nursing intervention.
AB  - The literature reveals there has been limited critical discussion of the inter
      relationship between urinary incontinence, the vulnerability of the skin and the
      clinical implications. This paper critically re-examines the literature to
      identify and apply relevant scientific principles and evidence to inform
      effective intervention. It includes background on the structure, function and
      disruption to the skin's barrier. The implications for fundamental and largely
      taken-for-granted nursing practices, such as washing the skin, are examined. The
      current state of knowledge is analysed, specifying the types of evidence
      available and its weaknesses, highlighting implications for a research agenda.

PMID- 16084929
TI  - Spitz naevi presenting as pyogenic granulomata.

PMID- 16084930
TI  - Oro-nasal fistula development and velopharyngeal insufficiency following primary
      cleft palate surgery--an audit of 148 children born between 1985 and 1997.
AB  - We present an audit of primary cleft palate surgery in our unit including rates
      of two important post-operative complications. Multidisciplinary audit clinics
      ran from March 1998 to April 2002 to follow up all local patients with a cleft
      lip or palate who had undergone primary palatal surgery in our unit. One hundred
      and forty eight patients were studied. Patient ages at follow-up ranged from 3
      years and 10 months to 17 years and 4 months. Two surgeons performed the primary
      surgery. One hundred and twenty eight Wardill-Kilner and 20 Von Langenbeck
      repairs were performed. We found a 4.7% rate of oro-nasal fistula development
      requiring surgical closure, and a 26.4% rate of velopharyngeal insufficiency
      (VPI) requiring subsequent pharyngoplasty. We noted that the type of cleft
      involved affected the rate of VPI, 16% of patients with unilateral cleft lip and
      palate versus 29.2% of patients with a solitary cleft palate requiring secondary
      surgery. Outcome of surgery was determined by a 'Cleft Audit Protocol for Speech'
      (CAPS) speech therapy assessment at follow-up clinics. Only 14.9% of all patients
      assessed demonstrated any degree of hypernasality. Our results compare favourably
      with other recent studies including the Clinical Standards Advisory Group (CSAG)
      report into treatment of children with cleft lip and palate.

PMID- 16084931
TI  - Group II mGluR-induced long term depression in the dentate gyrus in vivo is NMDA
      receptor-independent and does not require protein synthesis.
AB  - Long term depression (LTD) can be induced by low frequency stimulation (LFS) as
      well as by agonist activation of neurotransmitter receptors. Group II
      metabotropic glutamate receptors (mGluRs) play an essential role in the
      regulation of electrically-induced LTD in the hippocampus in vivo: LTD is
      inhibited by antagonists, and enhanced by agonists of group II mGluRs. Here we
      investigated induction of LTD by activation of group II mGluRs as well as the
      cellular mechanisms which might mediate group II mGluR-induced LTD. Rats were
      implanted with electrodes to enable chronic measurement of evoked potentials from
      medial perforant path-dentate gyrus synapses. Drug application was made through a
      cannula implanted into the ipsilateral cerebral ventricle. LTD could be induced
      by agonist activation of either group II mGluRs, or the group II mGluR subtype,
      mGluR3. Both, group II mGluR-induced LTD and mGluR3-induced LTD were not
      abolished by mRNA/protein synthesis inhibition. Furthermore, mGluR3-induced LTD
      was not inhibited by NMDA receptor antagonists or altered by L-type voltage-gated
      calcium channel blockers. Our data suggest that sole activation of group II
      mGluRs can mediate LTD in vivo. Intriguingly, this form of LTD is not dependent
      on protein synthesis or activation of NMDA receptors.

PMID- 16084932
TI  - Differential roles of mGlu8 receptors in the regulation of glutamate and gamma
      aminobutyric acid release at periaqueductal grey level.
AB  - We investigated the role of group III metabotropic glutamate (mGlu) receptors on
      glutamate and GABA releases at the periaqueductal grey (PAG) level by using in
      vivo microdialysis in rats. Intra-PAG perfusion of either L-(+)-2-amino-4
      phosphonobutyric acid (L-AP4, 100-300 microM), (RS)-4-phosphonophenylglycine
      ((RS)-PPG, 100-300 microM) selective agonists of group III mGlu receptors, or (S)
      3,4-dicarboxyphenylglycine ((S)-3,4-DCPG, 50-100 microM), a selective agonist of
      mGlu8 receptor, increased glutamate and decreased GABA extracellular
      concentrations. (RS)-alpha-methylserine-O-phosphate (MSOP, 0.5 mM), a selective
      group III receptor antagonist, perfused in combination with (S)-3,4-DCPG, L-AP4
      or (RS)-PPG, antagonised the effects induced by these agonists on both
      extracellular glutamate and GABA values. alpha-Methyl-3-methyl-4
      phosphonophenylglycine (UBP1112, 300 microM), a group III mGlu receptor
      antagonist, perfused in combination with (RS)-PPG or (S)-3,4-DCPG, antagonised
      the effects induced by these agonists. Intra-PAG perfusion with forskolin (100
      microM), an activator of adenylate cyclase, increased dialysate glutamate and
      GABA levels. Moreover, intra-PAG perfusion with N-[2-(p-bromocinnamyl
      amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89) (100 microM), a
      protein kinase (PKA) inhibitor, abolished the effect of (S)-3,4-DCPG on both
      glutamate and GABA releases. H-89, per se, did not modify glutamate release but
      reduced extracellular GABA value at the higher dosage used (200 microM). These
      data suggest that group III mGlu receptors in the PAG modulate the releases of
      glutamate and GABA conversely. In particular, both the facilitation of glutamate
      and the inhibition of GABA releases require the participation of coupling to
      adenylate cyclase and the subsequent activation of the PKA pathway.

PMID- 16084933
TI  - Structure of the O-polysaccharide and serological studies of the
      lipopolysaccharide of Proteus mirabilis 2002.
AB  - The structure of the O-polysaccharide of the lipopolysaccharide of Proteus
      mirabilis 2002 was elucidated by chemical methods and 1H and 13C NMR
      spectroscopy. It was found that the polysaccharide consists of branched
      pentasaccharide repeating units having the following structure: [structure in
      text]. The O-polysaccharide of P. mirabilis 2002 has a common tetrasaccharide
      fragment with that of P. mirabilis 52/57 from serogroup O29, and the
      lipopolysaccharides of the two strains are serologically related. Therefore,
      based on the structural and serological data, we propose to classify P. mirabilis
      2002 into the Proteus O29 serogroup as a subgroup O29a,29b.

PMID- 16084934
TI  - Construction of chimeric cyclodextrin glucanotransferases from Bacillus circulans
      A11 and Paenibacillus macerans IAM1243 and analysis of their product specificity.
AB  - Three DNA fragments of 7919 base pairs containing genes for beta-cyclodextrin
      glucanotransferase (CGTase, EC 2.4.1.19), an iron III dicitrate transport protein
      like protein and a partial coding sequence for putative ferrichrome ABC
      transporter from Bacillus circulans A11 were cloned and sequenced (GenBank
      Accession AF302787). The DNA sequence contained a CGTase open reading frame of
      2139 base pairs, which encoded a polypeptide of 713 amino acid residues. The
      signal peptide constituted the N-terminal 27 amino acid residues. The amino acid
      sequence was highly homologous to that of Bacillus sp. 1011 with 98.7% identity.
      The cloned CGTase gene contained its own promoter that directed the expression of
      the gene in Escherichia coli host cells. Chimeric construction against the alpha
      CGTase from B. macerans IAM1243 was carried out by means of three created
      restriction sites, XhoI, SpeI, and MfeI, introduced by mutagenesis in between
      domains A/B and C, C and D, and D and E, respectively, and the NdeI site within
      the domains A/B. The various chimeras with different combinations of domains and
      part of domains A/B were analyzed for their dextrinizing and CD-forming
      activities. Their activities were of three groups: chimeras with no dextrinizing
      and cyclization activities, chimeras with only dextrinizing activity, and
      chimeras with both dextrinizing and cyclization activities. Two chimeras in the
      latter group showed altered product specificity. The results located the amino
      acid segment essential for the product specificity at the C-terminal half of
      domains A/B. Further, the function of domains C and D in positioning domain E in
      the correct orientation and proximity to domains A/B is implicated.

PMID- 16084935
TI  - Comparative structural analysis of 5,6,7,9-tetra-O-acetyl-4,8-anhydro-1,3-dideoxy
      D-glycero-L-gluco-nonulose and its 1-O-acetylated analog, 1,2,3,4,6-penta-O
      acetyl-beta-D-galactopyranose using X-ray crystallography.
AB  - Comparative X-ray diffraction analysis of 5,6,7,9-tetra-O-acetyl-4,8-anhydro-1,3
      dideoxy-D-glycero-L-gluco-nonulose (1) and a structurally related analog,
      1,2,3,4,6-penta-O-acetyl-beta-D-galactopyranose (2), are reported. Both crystals
      have one molecule in the unit cell and the pyranose rings in both exist in the
      4C1 conformation.

PMID- 16084937
TI  - Translational medicine in genetic familial diseases: from the autopsy room to the
      molecular bench and vice versa.

PMID- 16084938
TI  - IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of
      the lung.
AB  - The association between IgG4 dysregulation and inflammatory pseudotumor (IPT) was
      first reported in sclerosing pancreatitis. Recently, we described IPTs of the
      liver and breast, into both of which many IgG4-positive plasma cells had
      infiltrated. In this study, we examined the clinical and histological features of
      9 cases of IPT (histologically corresponding to plasma cell granuloma) of the
      lung with an emphasis on IgG4-positive plasma cell infiltration. The lesions were
      characterized histologically by dense lymphoplasmacytic infiltrates intermixed
      with fibrosis and, in some cases, prominent eosinophilic infiltration, irregular
      narrowing of bronchioles entrapped in nodules, and an interstitial pneumonia
      pattern at the boundaries of nodules. Obliterative phlebitis was easily found in
      all cases, and 5 lesions also had obliterative arteritis. Immunostaining revealed
      many IgG4-positive plasma cells diffusely distributed within nodules, and the
      ratios of IgG4-positive to other plasma cells were extraordinarily high. Of the 9
      patients, 8 underwent surgical treatment and in 1 patient, lesion was diagnosed
      on transbronchial biopsy and effectively treated with corticosteroid. Two cases
      were associated with chronic sclerosing sialadenitis or lymphadenopathy, in which
      many IgG4-positive plasma cells were also identified by immunostaining. The
      clinicopathologic similarities between IPT of the lung and sclerosing
      pancreatitis suggest that IgG4-related immunopathologic processes might be
      involved in the pathogenesis of the pulmonary lesions.

PMID- 16084939
TI  - Thyroid transcription factor 1 expression in small cell carcinoma of the urinary
      bladder: an immunohistochemical profile of 44 cases.
AB  - Small cell carcinoma of the urinary bladder is a rare and aggressive tumor
      resembling small cell carcinoma of the lung. Thyroid transcription factor 1 (TTF
      1) expression is common in small cell carcinomas arising in the lung. However,
      studies of its expression in extrapulmonary small cell carcinomas have yielded
      varying results. Because information concerning the immunohistochemical profile
      of small cell carcinoma of the urinary bladder is limited, we investigated the
      immunoreactivity of this tumor to a battery of antibodies in a series of 44
      cases. Using 5-mum sections cut from paraffin-embedded tissue blocks,
      immunohistochemistry was performed to detect TTF-1, cytokeratin (CK) 7, CK20, and
      uroplakin antigenicity in 44 cases of small cell carcinoma of the urinary
      bladder. None of the patients had primary lung tumors. The TTF-1
      immunohistochemical stain showed nuclear positivity in 17 cases (39%). Positive
      immunostaining for CK7 was observed in 26 cases (59%). There was no positive
      staining with either CK20 or uroplakin. There was no correlation between TTF-1
      expression and survival (P = .27). In addition, TTF-1 expression did not
      correlate with clinicopathological characteristics, including age (P = .74), sex
      (P = .53), smoking history (P = .96), clinical stage (P = .10), pathological T
      stage (P = .50), lymph node metastasis (P = .40), and distant metastasis (P =
      .58). In summary, TTF-1 expression in small cell carcinoma of the urinary bladder
      was found in 39% of the tumors, demonstrating that this marker is expressed in
      small cell carcinomas other than those of pulmonary origin. Small cell carcinoma
      of the urinary bladder is positive for CK7 immunostaining in 59% of cases
      consistent with its origin from urothelium. Unlike urothelial carcinoma,
      expression of CK20 and uroplakin in small cell carcinoma of the urinary bladder
      is consistently negative, and thus, these stains do not appear to be useful in
      the diagnosis of this neoplasm. TTF-1 positivity is not a significant prognostic
      factor in small cell carcinoma of the urinary bladder.

PMID- 16084940
TI  - Poly(adenosine diphosphate-ribose) polymerase 1 expression in malignant melanomas
      from photoexposed areas of the head and neck region.
AB  - The family of the poly(adenosine diphosphate-ribose) polymerase (PARP) proteins
      is directly involved in genomic stability, DNA repair, and apoptosis by DNA
      damage. In this study, we evaluated the role of PARP-1 in melanoma and its
      prognostic importance. We studied by immunohistochemistry and Western blot
      analysis PARP-1 expression in a selected series of 80 primary melanoma of the
      head and neck region. The results were correlated with tumor thickness and
      patient's outcome. A follow-up of at least 3 years was available. Fifteen cases
      of benign melanocytic nevi were used as controls. Normal melanocytes showed only
      scattered, focal nuclear positivity and were considered as negative for PARP-1
      expression by immunohistochemistry (score, 0). Thirty cases of melanoma (37.5%)
      showed nuclear expression of PARP-1 in both radial and vertical growth phases.
      Western blot analysis showed the presence of a high signal for full-length PARP-1
      only in the cases with high immunohistochemical (nuclear) expression of protein
      (score, ++/+++) in both radial and vertical growth phase. A significant
      correlation was present between PARP-1 expression in vertical growth phase and
      the thickness of tumor lesion (P = .014); all but one tumor measuring less than
      0.75 mm showed no or low PARP-1 expression. No correlation was found between PARP
      1 expression in radial growth phase and tumor thickness (P = .38, data not
      shown). These data suggest that PARP-1 overexpression is a potential novel
      molecular marker of aggressive cutaneous malignant melanoma and a direct
      correlation between PARP-1-mediated inhibition of the apoptosis and biologic
      behavior of cutaneous malignant melanoma.

PMID- 16084941
TI  - Neuroendocrine differentiation in extrahepatic bile duct carcinomas and its
      prognostic significance.
AB  - Neuroendocrine differentiation is known to be one of the prognostic factors in
      many carcinomas. However, the characteristics of neuroendocrine differentiation
      are not well elucidated in extrahepatic bile duct (EBD) carcinomas. One hundred
      ninety-four cases of EBD carcinomas were analyzed using immunohistochemistry with
      synaptophysin and chromogranin. The tumors were graded as degree 0, 1, and 2 when
      the positive tumor cells were 5% or less, 6% to 25%, and 26% or more,
      respectively. Immunohistochemical results were compared with clinicopathologic
      variables and survival rate. Synaptophysin and chromogranin were positive in 54
      (27.8%) and 74 (38.1%) cases, respectively. Thirty-four cases (17.5%) were
      positive for both synaptophysin and chromogranin, 20 (10.3%) and 40 cases (20.6%)
      were positive only for synaptophysin and for chromogranin, respectively, and 100
      cases (51.6%) were negative for both markers. There was a significant survival
      difference between overall synaptophysin-positive (median, 27 months) and
      synaptophysin-negative (38 months) groups (P < .05). However, there was no
      survival difference between chromogranin-positive and chromogranin-negative
      groups. There was a significant survival difference between the dual-positive
      expression to synaptophysin and chromogranin group (median, 21 months) and the
      dual-negative expression group (median, 35 months; P < .05). In summary,
      synaptophysin expression was an important prognostic factor because synaptophysin
      positive cases showed a worse prognosis than synaptophysin-negative cases. The
      more tumor cells expressed chromogranin, the poorer the survival. Therefore,
      immunohistochemical studies for neuroendocrine differentiation may be helpful in
      routine pathological examinations for evaluating the survival and the prognosis
      of patients with EBD carcinomas.

PMID- 16084942
TI  - Fascin-1 expression in papillary and invasive urothelial carcinomas of the
      urinary bladder.
AB  - Fascin-1 is an actin-bundling protein that plays an important role in cell
      motility and adhesion. The level of fascin-1 is low or undetectable in normal
      epithelial cells. However, overexpression is reported in transformed epithelial
      cells and in several common types of carcinomas [Bioessays. 2002;24:359-361]. Up
      regulation of fascin-1 is associated with higher grades and with aggressive
      tumors with poorer prognoses. We found no report on the role or the protein
      expression of fascin-1 in urothelial carcinomas (UCs) of the urinary bladder. In
      this study, we examined by immunohistochemistry the expression of fascin-1 in the
      normal human transitional epithelium, benign vesical lesions, and different types
      of UCs. We found no detectable fascin-1 in the normal transitional epithelium.
      There was no increase of fascin-1 expression in cystitis cystica, cystitis
      glandularis, nephrogenic adenoma (n = 10), inverted papilloma (n = 5), and
      classic exophytic papilloma (n = 4) or in adjacent transitional epithelia
      associated with these conditions. Patchy or diffusely weak fascin-1 expression
      was observed in 42% (5/12) of superficial papillary UCs (Ta), and 95% (19/20) of
      invasive UCs (T2 or higher) demonstrated diffuse strong staining for fascin-1.
      The microinvasive foci in the lamina propria of UC (T1, n = 8) were also positive
      for fascin-1, although they were not as strongly stained as in the deeply
      invasive tumors. Interestingly, the neoplastic cells in the tips of microinvasive
      carcinomas were distinctly positive for fascin-1. There were significant numbers
      of fascin-1-positive cells (>50% of the neoplastic cells) in UCs in situ (n =
      10). These findings suggest an association between increased fascin-1 expression
      and increased invasiveness of carcinomas in the urinary bladder.

PMID- 16084943
TI  - Epstein-Barr virus is associated with all histological subtypes of Hodgkin
      lymphoma in Vietnamese children with special emphasis on the entity of lymphocyte
      predominance subtype.
AB  - Early acquisition of Epstein-Barr virus (EBV) infection is prevalent in
      developing countries. We studied infectious mononucleosis (IM) and the subtypes
      of Hodgkin lymphoma (HL) with the status of EBV infection in Vietnamese children.
      Among the 46 cases of HL, the male-to-female ratio was 38:8, and the mean age at
      presentation was 6.6 years. Similar to the subtype distribution in developed
      countries, cases were classified as nodular sclerosis (NSHL) subtype in 56.5% (n
      = 26), mixed cellularity (MCHL) in 23.9% (n = 11), lymphocyte-rich classic
      (LRCHL) in 8.7% (n = 4), lymphocyte depletion (LDHL) subtype in 4.4% (n = 2), and
      nodular lymphocyte predominance (NLPHL) subtype in 6.5% (n = 3). However, in situ
      hybridization for EBV-encoded RNA revealed that the tumor cells were positive in
      93.2% (41/44) of cases, including all 3 cases of nodular lymphocyte predominance
      HL. Expression of CD20 on Reed-Sternberg cells could be demonstrated in 17%
      (7/42) of classic HL. The high incidence of EBV in these cases of HL was
      correlated with an earlier mean age of presentation of primary EBV infection (ie,
      IM), at 5.3 years, in this patient population, compared with an average of 15 to
      19 years reported in developed countries. This study demonstrates that in an area
      with an earlier mean age of onset of EBV infection, nearly all cases of pediatric
      HL, including all histological patterns, may be related to EBV infection. The
      association of NLPHL with EBV is unusual, and the literature is reviewed and
      discussed.

PMID- 16084944
TI  - The effect of tissue fixation and processing on breast cancer size.
AB  - Precise measurement of an invasive breast cancer is crucial for pathological
      staging and subsequent patient management. Formalin fixation and histological
      processing may change tissue size, but there is no agreement on which state of
      the specimen, fresh or fixed, should be used for final tumor measurement. To
      determine the influence of fixation and processing on breast tumor size, a
      specific 1-dimensional measurement from 50 invasive breast tumors was recorded in
      fresh, fixed, and processed/mounted states. Tumors varied in maximum measured
      dimension from 4 to 20 mm and contained 10% to 90% estimated fibrous tissue
      (mean, 52.8%). In 96% of cases, there was no difference in measured size between
      fresh and fixed states. After final processing and mounting, a decrease in size
      from initial fresh measurement was noted in 40% of cases (mean difference, 2.4
      mm; maximum difference, 7 mm). In 9 cases (18%), the measured size increased by a
      maximum of 3 mm (mean, 1.7 mm) after processing/mounting. Twenty-one cases (42%)
      showed no change in measurement during the entire fixation and processing
      protocol. Increases in measured size were attributed largely to tissue expansion
      during histological sectioning/mounting. One can arguably measure the size of an
      invasive breast cancer from either the fresh or fixed state without affecting
      accuracy, but caution should be exercised in relying solely on the microscopic
      measurements.

PMID- 16084945
TI  - Juvenile sudden death in a family with polymorphic ventricular arrhythmias caused
      by a novel RyR2 gene mutation: evidence of specific morphological substrates.
AB  - We report on a family with a history of sudden death and effort-induced
      polymorphic ventricular arrhythmias. The index case was a 17-year-old boy who
      died suddenly and at postmortem had evidence of fibrofatty replacement in the
      right ventricular free wall, consistent with arrhythmogenic right ventricular
      cardiomyopathy, as well as calcium phosphate deposits within the myocytes. A
      molecular genetics investigation carried out in the paraffin-embedded myocardium
      of the subject and in blood samples of family members disclosed a missense
      mutation in exon 3 (230C-->T; A77V) of the cardiac ryanodine receptor type 2
      gene. The carriers showed effort-induced polymorphic ventricular tachycardia in
      the setting of normal resting electrocardiogram and trivial echocardiographic
      abnormalities, consistent with catecholaminergic polymorphic ventricular
      tachycardia. The observation of both arrhythmogenic right ventricular
      cardiomyopathy type 2 and catecholaminergic polymorphic ventricular tachycardia
      in the same family suggests that the two entities might correspond to different
      degrees of phenotypic expression of the same disease. This experience underscores
      the importance of a precise autopsy diagnosis in the case of sudden cardiac
      death, including molecular genetics, and the mission of pathologists to guide
      further clinical investigation of family members.

PMID- 16084946
TI  - PTEN expression in non-small-cell lung cancer: evaluating its relation to tumor
      characteristics, allelic loss, and epigenetic alteration.
AB  - The tumor suppressor PTEN encodes a lipid phosphatase that negatively regulates
      the phosphatidylinositol 3-kinase/AKT cell survival pathway. Mutations of this
      gene are common in brain, prostate, endometrial, and gastric cancers but occur
      rarely in non-small-cell lung cancer (NSCLC), although the PTEN protein is often
      lost in lung tumors. We have studied hypermethylation of the PTEN promoter, loss
      of heterozygosity (LOH) at microsatellites in chromosome 10q23 (surrounding and
      intragenic to the PTEN locus), and hypermethylation of PTEN's highly homologous
      pseudogene, PTENP1, and their association with PTEN protein loss in a surgical
      case series study of primary NSCLC. PTEN protein expression was reduced or lost
      in 74% (86/117) of tumors, with loss occurring more often in well to moderately
      differentiated tumors. In squamous cell carcinomas, PTEN loss occurred
      significantly more often in early-stage (stage I or II) disease. PTEN protein
      loss also occurred more frequently in tumors with low to no aberrant TP53
      staining. Methylation of PTEN occurred in 26% (39/151) of tumors, and LOH at
      10q23 was rare, occurring in only 19% (17/90) of informative tumors. Neither
      methylation nor LOH was a significant predictor of PTEN protein expression,
      although LOH occurred exclusively in early-stage disease. In NSCLC, loss of PTEN
      protein expression occurs frequently, although the mechanism responsible for loss
      is not clearly attributable to deletion or epigenetic silencing. PTEN loss may
      also be a favorable prognostic marker, although further studies are needed to
      confirm this finding.

PMID- 16084947
TI  - Correlation of AIB1 overexpression with advanced clinical stage of human
      colorectal carcinoma.
AB  - AIB1, a member of the steroid receptor coactivator 1 family, has been cloned on
      20q12 and is a candidate oncogene in human breast cancer. It is commonly
      amplified and overexpressed in several types of human cancers. In this study, we
      examined the expression of AIB1, as related to clinicopathologic features, in 85
      human colorectal cancers (CRCs). The status of the number of AIB1 copies, p53
      expression, and DNA ploidy was also analyzed. The overexpression of AIB1 was
      detected in 35% of CRCs. Amplification of AIB1 was observed in 10% of CRCs. In
      addition, the overexpression of AIB1 was observed more frequently in CRCs in
      later clinical stages (T3 N1 M0/T3 N0 2M1), compared with that in T3 N0 M0 stage
      (P < .05). These results suggest that overexpression of AIB1 might provide a
      selective advantage for the developmental growth and/or progression of subsets of
      CRCs. In addition, a significant correlation (P < .05) of overexpression of AIB1
      with p53 overexpression as well as with aneuploid DNA content was observed in
      these CRCs. The overexpression of p53 was also correlated significantly with CRC
      DNA ploidy (P < .05). Furthermore, there was a substantial population of CRCs
      showing overexpression of both AIB1 and p53 protein and all had aneuploid DNA
      content; most of these were in the later clinical stage. These findings suggest a
      possible convergence of AIB1 with a pathway involving p53, which might induce
      chromosomal instability and affect the clinical phenotype of a subset of CRCs.

PMID- 16084948
TI  - CD10 and BCL6 expression in the diagnosis of angioimmunoblastic T-cell lymphoma:
      utility of detecting CD10+ T cells by flow cytometry.
AB  - Angioimmunoblastic T-cell lymphoma (AITCL) is a histologically distinct and
      relatively common subtype of T-cell lymphoma. Although the putative normal cell
      counterpart is a mature CD4+ T cell, the precise cell of origin remains elusive.
      We evaluated cases with a diagnosis of AITCL to determine the specificity and
      utility of CD10 coexpression, particularly by flow cytometry (FCM), in
      facilitating this diagnosis. Coexpression of BCL6 was also assessed. Eight AITCL
      cases were evaluated histologically, immunohistochemically, and by 4-color FCM.
      Four cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS),
      were also analyzed. The lymphoma cells in all 8 AITCL cases were CD4+, CD45RO+ T
      cells, with classic extrafollicular meshworks of CD21/CD23/CD35+ follicular
      dendritic cells. Furthermore, all cases of AITCL cases contained interfollicular
      CD10+ cells by immunohistochemistry, and increased coexpression of CD10 on T
      cells was also detected in 6 of 8 cases by FCM. CD10 coexpression was not
      observed in all 4 PTCL-NOS cases. Although not specific for AITCL, increased
      numbers of BCL6+ cells were seen in AITCL as compared with PTCL-NOS. Double
      immunohistochemistry performed on an AITCL case with high numbers of BCL6+ cells
      highlighted coexpression of BCL6 and CD4 on the same cells. The finding suggests
      that AITCL may be a neoplasm of (possibly intrafollicular) CD10+, BCL6+, and CD4+
      memory T cells. Although our series is small, our results suggest that CD10
      coexpression may be a useful discriminant, particularly if the differential
      diagnosis is PTCL-NOS, and demonstrate that this can be determined by FCM.

PMID- 16084949
TI  - Is loss of heterozygosity at 9q22.3 (PTCH gene) and 19p13.3 (STK11 gene) involved
      in the pathogenesis of ovarian stromal tumors?
AB  - Some ovarian fibromas and rare fibrosarcomas are associated with Gorlin syndrome,
      which is caused by mutation in the human homologue of Drosophila patched gene
      (PTCH), localized on chromosome 9q22.3. The relationship between PTCH gene and
      sporadic ovarian tumors in the thecoma-fibroma group has not been well
      characterized. On the other hand, we have recently described loss of
      heterozygosity (LOH) at 19p13.3 in 2 sporadic fibromas with sex-cord elements. We
      have analyzed DNA from 8 fibromas, 6 cellular fibromas, 2 fibrothecomas, 9
      luteinized thecomas, and 2 fibrosarcomas of the ovary for LOH at 9q22.3 and
      19p13.3, using polymerase chain reaction amplification for 10 microsatellite
      markers. LOH at 9q22.3 was detected in 4 (67%) of 6 cellular fibromas, with the
      highest frequency at microsatellite marker D9S15, which localizes proximal to the
      PTCH gene. Of 9 luteinized thecomas, 2 (22%) also exhibited LOH at 9q22.3 with 3
      microsatellite markers other than D9S15. Allelic losses were not detected in any
      fibroma, fibrothecoma, or fibrosarcoma. LOH at 19p13.3 was found in 2 (25%) of 8
      fibromas, 3 (50%) of 6 cellular fibromas, and 1 (11%) of 9 luteinized thecomas.
      None of the 2 fibrothecomas or 2 fibrosarcomas showed LOH at 19p13.3. LOH at both
      9p22.3 and 19p13.3 was observed in 3 (50%) of 6 cellular fibromas, but not in
      luteinized thecomas. The results indicate that (1) LOH at both PTCH gene and
      STK11 gene is relatively frequent in cellular fibromas; (2) approximately a
      quarter of luteinized thecomas exhibited LOH of the PTCH gene; in both neoplasms,
      cellular fibromas and luteinized thecomas, LOH may play a role in their
      pathogenesis; and (3) sporadic cellular fibromas may arise through similar
      genetic pathways as cases of Gorlin syndrome.

PMID- 16084950
TI  - Expression and cellular localization of vascular endothelial growth factor A and
      its receptors in acute and chronic leukemias: an immunohistochemical study.
AB  - We aimed to study the expression of phosphorylated vascular endothelial growth
      factor receptor 2 (pVEGFR-2), a membrane-bound tyrosine kinase receptor to
      vascular endothelial growth factor, in 76 cases of leukemia and nonneoplastic
      myeloproliferative disease and in 8 reactive bone marrows. The microvessel
      density (MVD) and the expression of both pVEGFR-2 and its ligand, VEGFA, were
      evaluated in these cases. We used archival cases and immunohistochemistry with a
      monoclonal antibody generated by us to the autophosphorylation sites in the
      cytoplasmic tail of VEGFR-2 and von Willebrand factor antibody to evaluate MVD.
      Our results demonstrate increased expression of this phosphorylated receptor in
      the neoplastic cells in acute myeloid and lymphoblastic leukemias. This
      correlated with increased MVD and VEGFA expression by the neoplastic cells.
      Interestingly, there was nuclear relocation of this receptor in these diseases.
      This raises the possibility that pVEGFR-2 may be involved in the transcriptional
      regulation of these leukemias. Small molecule inhibitors to this receptor may
      therefore be a useful adjunct in the therapy for these diseases.

PMID- 16084951
TI  - Differential expression of cyclin D3 in ALK+ and ALK- anaplastic large cell
      lymphoma.
AB  - As defined in the World Health Organization classification, anaplastic large cell
      lymphoma (ALCL) is a distinct type of non-Hodgkin lymphoma of T/null cell
      lineage, a subset of which is associated with translocations involving 2p23
      resulting in expression of anaplastic lymphoma kinase (ALK). The most common
      translocation, the t(2;5)(p23;q35), results in expression of nucleophosmin (NPM)
      ALK. NPM-ALK has been shown to activate signal transducer and activator of
      transcription (STAT) 3, a transcriptional regulator of cyclin D3. In this study,
      we assessed cyclin D3 expression in 2 ALK+ ALCL cell lines (Karpas 299 and SU
      DHL1) and 1 ALK- ALCL cell line (Mac2A) by Western blot analysis. We also
      assessed cyclin D3 expression in 52 ALCL tumors (32 ALK+, 20 ALK-) by
      immunohistochemistry using tissue microarrays. These results were compared with
      phosphorylated (activated) STAT3 (pSTAT3) expression. Both ALK+ ALCL cell lines,
      but not the ALK- ALCL cell line, expressed cyclin D3 and pSTAT3. Cyclin D3 was
      expressed in 25 (78%) of 32 ALK+ ALCL tumors and in 4 (20%) of 20 ALK- ALCL
      tumors (P < .001, Fisher exact test ). In ALK+ ALCL tumors, the mean percentage
      of cyclin D3-positive tumor cells was 40.6% compared with 5.1% in ALK- ALCL
      tumors (P < .001, Mann-Whitney U test). The percentages of cyclin D3-positive and
      pSTAT3-positive tumor cells were positively correlated (Spearman R = 0.35, P =
      .036). We conclude that cyclin D3 is differentially expressed in ALK+ and ALK-
      ALCL and that high expression levels of cyclin D3 in ALK+ ALCL may be
      attributable to STAT3 activation.

PMID- 16084952
TI  - Tissues from population-based cancer registries: a novel approach to increasing
      research potential.
AB  - Population-based cancer registries, such as those included in the Surveillance,
      Epidemiology, and End-Results (SEER) Program, offer tremendous research potential
      beyond traditional surveillance activities. We describe the expansion of SEER
      registries to gather formalin-fixed, paraffin-embedded tissue from cancer
      patients on a population basis. Population-based tissue banks have the advantage
      of providing an unbiased sampling frame for evaluating the public health impact
      of genes or protein targets that may be used for therapeutic or diagnostic
      purposes in defined communities. Such repositories provide a unique resource for
      testing new molecular classification schemes for cancer, validating new biologic
      markers of malignancy, prognosis and progression, assessing therapeutic targets,
      and measuring allele frequencies of cancer-associated genetic polymorphisms or
      germline mutations in representative samples. The assembly of tissue microarrays
      will allow for the use of rapid, large-scale protein-expression profiling of
      tumor samples while limiting depletion of this valuable resource. Access to
      biologic specimens through SEER registries will provide researchers with
      demographic, clinical, and risk factor information on cancer patients with
      assured data quality and completeness. Clinical outcome data, such as disease
      free survival, can be correlated with previously validated prognostic markers.
      Furthermore, the anonymity of the study subject can be protected through rigorous
      standards of confidentiality. SEER-based tissue resources represent a step
      forward in true, population-based tissue repositories of tumors from US patients
      and may serve as a foundation for molecular epidemiology studies of cancer in
      this country.

PMID- 16084953
TI  - Differential expression of p63 isotypes (DeltaN and TA) in salivary gland
      neoplasms: biological and diagnostic implications.
AB  - To determine the association between the expression of p63 gene isoforms (TA and
      DeltaN) and salivary gland tumorigenesis, we performed reverse transcription
      polymerase chain reaction analysis of these markers in 71 benign and malignant
      salivary gland neoplasms. The results were correlated with the expression of
      Notch ligand JAG1 gene and the clinicopathologic features and the full-length p63
      protein expression by immunohistochemistry. Both p63 isoforms were either
      negative or weakly expressed in normal salivary gland tissues. TAp63 was highly
      expressed in most benign tumors and was either negative or weakly positive in
      most carcinomas. Conversely, DeltaNp63 was negative or faintly positive in most
      benign neoplasms and was highly expressed in adenoid cystic, mucoepidermoid, and
      myoepithelial carcinomas. Immunohistochemical analysis using anti-full-length p63
      protein showed ubiquitous nuclear staining in basal and myoepithelial cells in
      both benign and malignant neoplasms. JAG1 was expressed in most benign and
      malignant tumors and did not correlate with p63 isoforms expression. We conclude
      that (1) p63 isoforms are differentially expressed in most benign and malignant
      tumors and may play distinct biological roles in certain salivary gland
      neoplasms; (2) p63 immunostaining do not correlate with the isoforms expression;
      and (3) isoform-specific antibodies are required for better cellular localization
      and biological correlations.

PMID- 16084954
TI  - Prognostic significance of expressions of cell-cycle regulatory proteins in
      gastrointestinal stromal tumor and the relevance of the risk grade.
AB  - Gastrointestinal stromal tumors (GISTs) have a wide spectrum of biologic behavior
      ranging from benign to malignant. Risk grading based on tumor size and mitotic
      counts has been proposed in an effort to predict the adverse outcome of GIST in
      the literature so far. Recent molecular studies have reported the prognostic
      values of several parameters, including alteration of cell-cycle regulators. The
      aim of this study was to elucidate the prognostic values of risk grade and
      alterations of cell-cycle-related proteins, including Ki-67, cyclin A, cyclin B1,
      cyclin D1, cyclin E, p16, p21, p27, p53, cdc2, and cdk2, in addition to the
      conventional factors. Eighty cases of primary c-kit-positive GISTs were
      classified into 2 cases of very-low-risk grade, 20 cases of low-risk grade, 25
      cases of intermediate-risk grade, and 33 cases of high-risk grade. The risk grade
      was correlated with the presence of metastases and/or recurrence. A high level of
      Ki-67 and cyclin A expression was correlated with risk grade (P = .0027 and
      .0441, respectively). Overexpression of G2-M regulators, such as cyclin A, cyclin
      B1, and cdc2, was associated with the Ki-67 labeling index (LI) (P = .0007,
      .0475, and .0040, respectively). According to univariate analysis, tumor grade
      (high risk), tumor size (> or =5 cm), mitotic counts (> or =5/50 high-power
      fields), Ki-67 LI (> or =4.92%), cyclin A LI (> or =1.61%), and cdc2 LI (> or
      =1.25%) were all found to be significantly associated with a shorter period of
      disease-free survival (P = .0001, .0270, .0004, .0001, .0001, and .0011,
      respectively). According to multivariate analysis, both high Ki-67 LI and high
      risk grade were found to be significantly associated with a shorter period of
      disease-free survival (P = .0083 and .0246, respectively). In conclusion, our
      results strongly support the hypothesis that Ki-67 LI and risk grade are useful
      for predicting the aggressive biologic behavior of GISTs. Furthermore, alteration
      of G2-M regulators, such as cyclin A, cyclin B1, and cdc2, is also a useful
      marker for predicting aggressive behavior and play an important role, at least in
      part, in the cell proliferation of GIST.

PMID- 16084955
TI  - Well-differentiated extraosseous chondrosarcoma of the foot with pulmonary
      metastases.
AB  - We report a case of a 38-year-old man with a well-differentiated extraosseous
      chondrosarcoma of the foot. This case is unusual because the tumor originated in
      the soft tissues of the foot and developed pulmonary metastases. It is also
      interesting to note that at the time of recurrence 8 years later, the lesion
      invaded the third metatarsophalangeal joint and adjacent bones. Well
      differentiated chondrosarcoma resembling hyaline cartilage, primary in soft
      tissue, is a rare histological type, and only a few cases have been reported in
      the foot. The patient is alive and well 4.5 years after resection of the foot
      tumor and partial resection of the lung metastases.

PMID- 16084956
TI  - Multilocular thymic cyst associated with follicular hyperplasia:
      clinicopathologic study of 4 resected cases.
AB  - We report here 4 cases of multilocular thymic cysts (MTCs) with reactive lymphoid
      follicular hyperplasia. They were admitted to our hospital to examine anterior
      mediastinal masses demonstrated on chest computed tomographic scans. Three
      patients presented high-grade intermittent fever, and 2 patients were associated
      with Sjogren syndrome with elevated serum antinuclear antibody levels. All
      patients were subjected to extended thymectomy. Interestingly, their fever
      disappeared immediately after surgery. Histologically, the lesions were
      characterized by several cystic spaces separated by various thick walls with
      dense lymphoid tissue containing large reactive germinal centers. The inner cyst
      walls were lined by flattened cuboidal epithelia in some portions. Columnar
      epithelia with focal cilia were partially observed in 2 cases. These pathological
      findings led to a diagnosis of MTCs that were thought to result from cystic
      transformation of medullary duct derivatives by acquired inflammatory processes.
      The pathological findings, together with clinical courses of our cases, suggest
      that inflammation accompanied by autoimmune diseases may play, in part, an
      important role in the development of MTCs.

PMID- 16084957
TI  - Globular hepatic amyloid: a diagnostic peculiarity that bears clinical
      significance.
AB  - Hepatic amyloid deposition in the form of globular inclusions is a rare
      occurrence. Only 24 such cases have been reported to date. Its clinical and
      pathological significance are undefined. Unawareness of such a pattern can cause
      diagnostic confusion. We herein describe a case of globular hepatic amyloid in a
      patient with a B-cell lymphoma and chronic hepatitis C. The findings in our case
      support the literature data in that (1) it is often an incidental finding during
      workup for other coexisting conditions and (2) its morphology is peculiar but can
      be recognized with ease if one is aware of its existence. Our case also provides
      new insights into this condition. First, it represents the first nonautopsy case
      to demonstrate that globular hepatic amyloid is an indication of systemic
      amyloidosis, thus emphasizing the clinical importance of the recognition of this
      condition. Second, in our case, there was a coexisting B-cell lymphoma, the
      constituent cells of which showed immunoglobulin lambda light chain restriction,
      and patient's serum lambda light chain was elevated. However, light chain
      restriction was not demonstrated in the globular inclusions, and there was no
      evidence of monoclonal gammopathy by serum electrophoresis. Whether
      immunoglobulin light-chain abnormality played a causal role in this condition is
      to be determined.

PMID- 16084958
TI  - Persistent Yersinia pestis antigens in ischemic tissues of a patient with
      septicemic plague.
AB  - In November 2002, a couple from New Mexico traveled to New York where both had
      fever and unilateral inguinal adenopathy. The husband was in septic shock when he
      sought medical care and was admitted to an intensive care unit, where he
      developed ischemic necrosis of his feet which later required bilateral
      amputation. Yersinia pestis was grown from his blood. Immunohistochemical assays
      using anti-Y pestis antibodies demonstrated multiple bacteria and granular
      antigens in and around vessels of the ischemic amputation tissues obtained 20
      days after initiation of antibiotics; however, no evidence of Y pestis was
      present in viable tissues. Immunohistochemical evidence of Y pestis inside
      vessels of gangrenous feet in this patient underscores the importance of adequate
      excision of necrotic or partially necrotic tissues because antibiotics cannot be
      effectively delivered to necrotic and poorly perfused tissues.

PMID- 16084959
TI  - Disseminating anaplastic brainstem oligodendroglioma associated with allelic loss
      in the tumor suppressor candidate region D19S246 of chromosome 19 mimicking an
      inflammatory central nervous system disease in a 9-year-old boy.
AB  - We report the case of a 9-year-old boy clinically presenting with severe
      headache, vomiting, head retroflexion, nystagmus, and ataxia. Magnetic resonance
      imaging showed brainstem enlargement leading to the diagnosis of an inflammatory
      process. In addition, the clinical picture, a monocytic cerebrospinal fluid
      pleocytosis with elevated protein and lactate and serum IgM antibodies to
      Mycoplasma pneumoniae favored this diagnosis. Subsequently, corticosteroid
      treatment rapidly improved clinical symptoms, and lesions declined in subsequent
      neuroradiological examinations. However, 2 months later, fulminant disease
      progression led to brain death. Final neuroradiological examination favored
      meningoencephalitis. The autopsy revealed brain swelling and brainstem softening
      with a superficial gelatinous mass extending along the spinal cord. Finally, a
      disseminating anaplastic oligodendroglioma with allelic loss of the D19S246 tumor
      suppressor candidate locus of chromosome 19 was diagnosed. To our knowledge, this
      is the first case of a disseminating anaplastic brainstem oligodendroglioma
      associated with this specific allelic loss occurring in childhood.

PMID- 16084960
TI  - Claudin expression in breast tumors.

PMID- 16084962
TI  - New considerations for IGFBP-3 determination in human serum.

PMID- 16084963
TI  - Integrating spatio-temporal information in environmental monitoring data--a
      visualization approach applied to moss data.
AB  - Large-scale environmental monitoring data being sparse and collected on irregular
      grids, which may differ from year to year, are difficult to analyse and present.
      The traditional techniques from statistics and Geographic Information Systems
      (GIS) may not be useful given the often relatively small sample size combined
      with varying sampling density. In this study, the freeware visualization package
      XmdvTool was used for integration and exploration of monitoring data from three
      surveys of terrestrial mosses. Data on contents of Cu, Ni, Pb, V and Zn in mosses
      within an area of 300x300 km in southern Sweden, sampled in 1985 (177 samples),
      1990 (156 samples) and 1995 (188 samples), were integrated and visualized using
      parallel coordinate and scatterplot display techniques. Several interesting
      findings about multi-element composition of samples, as well as changing temporal
      trends in the relations of five metals were made during interactive visual
      discovery. Visualization techniques for high-dimensional data may have
      limitations considering, for example, number of variables, ranges of data values,
      and spatial scales. Nevertheless, interactive data manipulation tools encourage
      the process of visual exploration, and the unique way of integrating spatial,
      temporal and multi-element components of moss data provided visual insights that
      are not possible to gain with traditional analysis tools.

PMID- 16084964
TI  - An inexact fuzzy two-stage stochastic model for quantifying the efficiency of
      nonpoint source effluent trading under uncertainty.
AB  - Reduction of nonpoint source (NPS) pollution from agricultural lands is a major
      concern in most countries. One method to reduce NPS pollution is through land
      retirement programs. This method, however, may result in enormous economic costs
      especially when large sums of croplands need to be retired. To reduce the cost,
      effluent trading can be employed to couple with land retirement programs.
      However, the trading efforts can also become inefficient due to various
      uncertainties existing in stochastic, interval, and fuzzy formats in agricultural
      systems. Thus, it is desired to develop improved methods to effectively quantify
      the efficiency of potential trading efforts by considering those uncertainties.
      In this respect, this paper presents an inexact fuzzy two-stage stochastic
      programming model to tackle such problems. The proposed model can facilitate
      decision-making to implement trading efforts for agricultural NPS pollution
      reduction through land retirement programs. The applicability of the model is
      demonstrated through a hypothetical effluent trading program within a
      subcatchment of the Lake Tai Basin in China. The study results indicate that the
      efficiency of the trading program is significantly influenced by precipitation
      amount, agricultural activities, and level of discharge limits of pollutants. The
      results also show that the trading program will be more effective for low
      precipitation years and with stricter discharge limits.

PMID- 16084965
TI  - Use of starch and potato peel waste for perchlorate bioreduction in water.
AB  - The cost of carbon substrates for microbial reduction of perchlorate (ClO(4)(-))
      is central to the success and competitiveness of a sustainable bioremediation
      strategy for ClO(4)(-). This study explored the potential application of starch
      in combination with an amylolytic bacterial consortia and potato peel waste for
      ClO(4)(-) bioreduction. We obtained a potent amylolytic bacterial consortium that
      consisted of a Citrobacter sp. S4, Streptomyces sp. S2, Flavobacterium sp. S6,
      Pseudoxanthomonas sp. S5, Streptomyces sp. S7, and an Aeromonas sp. S8 identified
      by 16S rDNA sequencing. ClO(4)(-) concentration substantially decreased in
      purified starch medium inoculated with the amylolytic bacterial consortium and
      Dechlorosoma sp. perclace. Potato peel waste supported ClO(4)(-) reduction by
      perclace with the rate of ClO(4)(-) reduction being dependent on the amount of
      potato peels. Over 90% ClO(4)(-) removal was achieved in 4 days in a single time
      point experiment with 2% (w/v) potato peels waste. ClO(4)(-) reduction in a non
      sterile 0.5% potato peel media inoculated with perclace occurred with an initial
      concentration of 10.14+/-0.04 mg L(-1) to 2.87+/-0.4 mg L(-1) (71.7% reduction)
      within 5 days. ClO(4)(-) was not detected in the cultures in 6 days. In a non
      sterile 0.5% potato media without perclace, ClO(4)(-) depletion occurred slowly
      from an initial value of 9.99+/-0.15 mg L(-1) to 6.33+/-0.43 mg L(-1) (36.63%
      reduction) in 5 days. Thereafter, ClO(4)(-) was rapidly degraded achieving 77.1%
      reduction in 7 days and not detected in 9 days. No susbstantial reduction of
      ClO(4)(-) was observed in the sterile potato peel media without perclace in 7
      days. Redox potential of the potato peel cultures was favorable for ClO(4)(-)
      reduction, decreasing to as low as -294 mV in 24 h. Sugar levels remained very
      low in cultures effectively reducing ClO(4)(-) and was substantially higher in
      sterilized controls. Our results indicate that potato peel waste in combination
      with amylolytic microorganisms and Dechlorosoma sp. perclace can be economically
      used to achieve complete ClO(4)(-) removal from water.

PMID- 16084966
TI  - Comparative biomonitoring of leachates from hazardous solid waste of two
      industries using Allium test.
AB  - Hazardous industrial wastes are inevitable source of environmental pollution.
      Leachates from these wastes might contaminate the origins of potable water and
      affect human health. The study was carried out to determine the possible
      genotoxic effects of leachates from solid waste of a metal and dye industry using
      the Allium cepa chromosome aberrations assay. The 10% leachates were prepared
      from solid wastes obtained from both the industries and examined for the presence
      of heavy metal content and genotoxicity. To simulate the field and laboratory
      conditions, A. cepa bulbs were exposed through soil and aqueous medium for 48 h
      to 2.5-10% leachates. The results revealed that both metal waste leachate (MWL)
      and dye waste leachate (DWL) contained high concentrations of chromium, nickel
      and iron that significantly induced cytogenetic alterations. Significant
      inhibition of mitotic index (MI), inductions of chromosomal/mitotic aberrations
      (CA/MA) and micronuclei (MN) formation were found in all experimental groups
      exposed to MWL and DWL. The effects observed were concentration dependent and the
      frequency of aberrations was higher with treatment of MWL than DWL. The MI was
      severely inhibited at 10% aqueous exposure it was 4.59+/-0.69 (P<0.001) in MWL
      and almost half to that induced by DWL that was 8.62+/-0.69 (P<0.05). Significant
      frequency of CA/MA and MN induced by MWL was 14.21 (P<0.001) and 0.33 (P<0.001)
      whereas CA/MA and MN induced by DWL was 7.81 (P<0.001) and 0.13 (P<0.05) in the
      aqueous medium. The investigations inferred that abnormalities caused by MWL were
      higher than DWL both in soil and aqueous media. These toxic responses may have
      relied on raised heavy metal concentrations of metal-based than dye industrial
      wastes.

PMID- 16084967
TI  - Effect of alkaline pH and associated Zn on the concentration and total uptake of
      Cd by lettuce: comparison with predictions from the CLEA model.
AB  - An eight-fold underestimate of the potential Cd exposure to humans via ingestion
      of lettuce grown in moderately alkaline soil has been measured experimentally.
      Current models of Cd uptake by leafy vegetables, which are used in risk
      assessment (e.g. CLEA in UK) predict higher concentration factors in acid than in
      alkaline soils. Experimental evidence shows that Cd uptake, although it decreases
      with increasing pH from acid to neutral soils, increases again in alkaline soils,
      confirming recent finding from other workers. The concentration of Zn in the soil
      also significantly affects the uptake of Cd, although this is not included in the
      current prediction models either. The effect of Zn on the uptake of Cd by plants
      is greater in slightly alkaline soils (pH 7.7) than in slightly acidic or neutral
      soils. High concentrations of Zn in soil (1000 mg/kg), which are often associated
      with elevated Cd levels, further increase the Cd concentration factor to values
      12 times higher than that predicted by the CLEA model. This is due in part to the
      effect of the high soil Zn on reducing the above-ground biomass of the plants.

PMID- 16084968
TI  - Mapping risk of cadmium and lead contamination to human health in soils of
      Central Iran.
AB  - In order to map Cd and Pb contamination in the soils of the region of Isfahan,
      Central Iran, we performed indicator kriging on a set of 255 topsoil samples (0
      20 cm) gathered irregularly from an area of 6800 km(2). The measured Cd
      concentrations exceeded the Swiss guide value in more than 80% of the samples
      whereas Pb concentrations exceeded the respective guide value only in 2% of the
      samples. Based on the simulated conditional distribution functions, the
      probability of exceeding the concentration of Cd and Pb from the specific
      threshold was computed. The results indicated that in most parts of the region
      the probability of contamination by Cd is very large (>0.95) whereas it is small
      (<0.5) for Pb. Based on a misclassification analysis, we chose the probability of
      0.45 as optimum probability threshold to delineate the polluted from unpolluted
      areas for Cd. In addition, we performed a loss analysis to separate risks to
      human health from potential losses due to remediation costs. Based on this
      analysis a probability threshold of 0.8 was found to be the optimum threshold for
      the classification of polluted and unpolluted areas in the case of Cd. Health
      risks were found to be larger in the western parts of the region.
      Misclassification analysis was sufficient for risk mapping for Pb as its
      concentration did not reach risk levels for human health. A probability of 0.7
      for Pb was found to be the optimum threshold for the delineation of polluted and
      unpolluted lands.

PMID- 16084969
TI  - Use of temporal/seasonal- and size-dependent bioaerosol data to characterize the
      contribution of outdoor fungi to residential exposures.
AB  - With the use of published temporal/seasonal and particle size distribution of
      outdoor bioaerosol data and meteorological information in the subtropical
      climate, we characterized the airborne fungal concentration
      indoor/outdoor/personal exposure relationships in a wind-induced naturally
      ventilated residence. We applied a size-dependent indoor/outdoor ratio model
      coupled with a compartmental lung model based on a hygroscopic growth factor as a
      function of relative humidity on aerodynamic diameter and concentration of fungal
      spores. The higher indoor airborne fungal concentrations occurred in early
      morning and late afternoon in which median values were 699.29 and 626.20 CFU m(
      3) in summer as well as 138.71 and 99.01 CFU m(-3) in winter, respectively, at 2
      am and 8 pm. In the absence of indoor sources, summer has higher mean
      indoor/outdoor ratios of airborne fungal concentration (0.29-0.58) than that in
      winter (0.12-0.16). Lung region of extrathoracic (ET) has higher fungal
      concentration lung/indoor ratios (0.7-0.8) than that in bronchial (BB; 0.41
      0.60), bronchiolar (bb; 0.12-0.40), and alveolar-interstitial (AI); 0.01-0.24)
      regions. The highest airborne fungal deposition dose (95th-percentile is 4600
      CFU) occurred in 11 pm-5 am in region AI in that the 95th-percentile fungal
      deposition rate was 0.22 CFU s(-1).

PMID- 16084970
TI  - Urinary 1-hydroxypyrene in children living in city and rural residences in
      Denmark.
AB  - AIMS: The present study aims to assess the biological uptake in children of
      polycyclic aromatic hydrocarbons measured as 1-hydroxypyrene in urine from
      children living in city and rural residences. METHODS: 103 children living in
      Copenhagen and 101 children living in rural residences of Denmark collected urine
      samples Monday to Friday morning. Each day, the family filled in a printed diary
      that included questions about the time and activity patterns of the child.
      Multiple regression analyses were used to identify predictors of the excreted 1
      hydroxypyrene level. RESULTS: During the week, the children excreted on average
      0.07 [95% CI: 0.01-0.41] mumol urinary 1-hydroxypyrene per mol creatinine.
      Children living in urban residences excreted 0.02 [95% CI: 0.01-0.05] mumol more
      1-hydroxypyrene than children living in rural residences. This was confirmed in
      the multiple regression analysis showing a 29% (95% CI: 2-64%) higher excretion
      among urban children than rural children. Moreover, the regression analysis
      showed that for each hour per day spent outside the children excreted 58% (1.58
      [1.22-2.03]) more 1-hydroxypyrene in urine. CONCLUSION: The present study
      indicates that children living in urban residences are more exposed to PAH than
      children living in rural residences. Time spent outdoors increased the excretion
      of 1-hydroxypyrene, which was most evident among urban children. Higher
      concentrations of ambient air pollution in urban areas may explain this finding.
      No influence of environmental tobacco smoke, cooking habits, and heating
      facilities was detected.

PMID- 16084971
TI  - Blood lead levels in lactating cows reared around polluted localities; transfer
      of lead into milk.
AB  - Lead is pervasive environmental pollutant with potential public health hazard as
      a contaminant of food from animal origin. The present study examines the blood
      and milk lead level in animals reared in areas around different industrial
      activities and to find out correlation between blood and milk lead levels in
      lactating cows. Blood and milk samples (n=149) were collected from animals reared
      around steel processing unit (n=22), lead-zinc smelter (n=21), aluminum
      processing plant (n=25), rock phosphate mining area cum phosphate fertilizer
      plant (n=21), coal mining areas (n=46) and closed lead but functional zinc
      smelter (n=14). Samples were also collected from randomly chosen 52 lactating
      cows reared in non-polluted areas to serve as controls. Significantly (P<0.05)
      higher blood lead level was recorded in animals reared around lead-zinc smelting
      factories followed by closed lead but functional zinc smelter, aluminum
      processing unit and steel manufacturing plant, as compared to values recorded for
      control animals. The highest milk lead level (0.84+/-0.11 microg/ml) was detected
      in animals reared in the vicinity of lead-zinc smelting unit followed by aluminum
      processing plant and steel processing unit. Analysis of correlation between blood
      lead levels and lead excretion in milk through sorting the blood lead values into
      nine different ranges irrespective of site of collection of samples (n=201)
      revealed significant correlation (r=0.469 at P<0.01) between blood and milk lead
      concentrations. The lactating cows with blood lead levels above 0.20 microg/ml
      (Groups 5 to 9) had significantly (P<0.05) higher milk lead excretion than those
      with blood lead levels from non-detectable to 0.20 microg/ml (Groups 1 to 4).
      Pearson correlation analysis between blood and milk lead concentrations in 122
      animals with blood lead <or=0.20 microg/ml showed non-significant correlation
      (r=0.030 at P<0.05) but a significant correlation was observed between these two
      parameters with blood lead level above >0.20 microg/ml indicating that the
      excretion of lead through milk increases with the increase in blood lead level
      above 0.20 microg/ml.

PMID- 16084972
TI  - Variations of Cd/Pb and Zn/Pb ratios in Taipei aerosols reflecting long-range
      transport or local pollution emissions.
AB  - Along with windblown dust, large quantities of pollutants are annually brought
      out of continental China by the westerlies in winter and spring; thereafter, they
      are partly subjected to transport by northeastern monsoon winds to Taiwan. To
      characterize the heavy metal composition differences between long-range
      transported and local aerosols and to evaluate metal contributions from long
      range transported aerosols during the northeastern monsoon season, both PM(10)
      and PM(2.5) aerosols collected from Taipei, Taiwan from February 2002 to March
      2003 were analyzed for three selected heavy metals, namely Pb, Cd and Zn using
      ICP-MS. Monthly patterns show that Pb concentrations in winter (62 ng/m(3)) were
      over two times higher than those in the other seasons, which is attributed to
      long-range transport from areas under development in China. Low Cd/Pb (0.017) and
      Zn/Pb (1.82) ratios were measured in aerosols collected during the Asian dust
      period, in which the ambient aerosols consisted predominantly of long-range
      transported pollutants. By contrast, high Cd/Pb (0.030) and Zn/Pb (3.44) ratios
      were observed during the summer monsoon season, in which aerosols were dominated
      by local pollutant emissions. Cd/Pb and Zn/Pb ratios appear to be successfully
      applied to identify the pollutants originating principally from the long-range
      transport or from local emissions. In addition, by assuming that a significant
      fraction of heavy metals associated with coarse airborne dust have settled to the
      sea prior to reaching Taiwan in spring, a mechanism is suggested to explain why
      higher anthropogenic metal concentrations occurred in winter than those in dust
      rich spring.

PMID- 16084973
TI  - Sorption and redox processes controlling arsenic fate and transport in a stream
      impacted by acid mine drainage.
AB  - Reigous acid creek originating from the Carnoules tailings impoundment supplies
      high concentrations of arsenic under soluble (up to approximately 4 mg/l) and
      particulate (up to 150 mgAs/g) phases to the Amous river, situated at the
      drainage basin of the Rhone river (Southern France). The metalloid is present as
      As(III) (>95%) in Reigous creek water while As(V) predominates (50-80%) in the
      solid phase, i.e. schwertmannite. At the confluence between acid (pH<5) creek and
      alkaline Amous river, As(III) concentrations decrease ten-fold through dilution
      and formation of As-rich ferrihydrite (As/Fe=0.02-0.1) containing 10-30% As(III).
      However, these attenuation processes are not efficient in the summer heatwave of
      2003 since As concentrations in Amous river water (>or=20 microg/l) and As/Fe
      ratios in particulate matter (>or=0.07) are closed to those of Reigous creek
      (<or=22 microg/l and <or=0.02, respectively) or even higher. Downstream the
      confluence, processes involved in the transport of aqueous As along Amous river
      flowpath vary seasonally. Arsenic is transported conservatively in the aqueous
      phase away from the confluence in the cooler months; thus, dilution by unpolluted
      tributaries is the only process that decreases As concentrations. However,
      As(III) is rapidly oxidized and As(V) remains in solution. In contrast, during
      the warm season, desorption from As-rich sediment occurs which results in an
      increase of As(V) and As(III) concentrations along Amous river flow until they
      reach up to approximately 20 microg/l each. Therefore, Amous river seems not to
      be totally recovered from mine-related arsenic contamination after 3.5 km and may
      affect freshwater resources further downstream.

PMID- 16084974
TI  - Fine particle number and mass concentration measurements in urban Indian
      households.
AB  - Fine particle number concentration (D(p)>10 nm, cm(-3)), mass concentrations
      (approximation of PM(2.5), microg m(-3)) and indoor/outdoor number concentration
      ratio (I/O) measurements have been conducted for the first time in 11 urban
      households in India, 2002. The results indicate remarkable high indoor number and
      mass concentrations and I/O number concentration ratios caused by cooking.
      Besides cooking stoves that used liquefied petroleum gas (LPG) or kerosene as the
      main fuel, high indoor concentrations can be explained by poor ventilation
      systems. Particle number concentrations of more than 300,000 cm(-3) and mass
      concentrations of more than 1000 microg m(-3) were detected in some cases. When
      the number and mass concentrations during cooking times were statistically
      compared, a correlation coefficient r>0.50 was observed in 63% of the households.
      Some households used other fuels like wood and dung cakes along with the main
      fuel, but also other living activities influenced the concentrations. In some
      areas, outdoor combustion processes had a negative impact on indoor air quality.
      The maximum concentrations observed in most cases were due to indoor combustion
      sources. Reduction of exposure risk and health effects caused by poor indoor air
      in urban Indian households is possible by improving indoor ventilation and
      reducing penetration of outdoor particles.

PMID- 16084975
TI  - Characteristics of PCDD/F congener distributions in gas/particulate phases and
      emissions from two municipal solid waste incinerators in Taiwan.
AB  - Partitioning of PCDD/F (polychlorinated dibenzo-p-dioxins and polychlorinated
      dibenzofuran) congeners between gaseous and particulate phases and removal
      efficiencies of the existing air pollution control devices (APCDs) for PCDD/Fs at
      two large-scale municipal waste incinerators (MWIs) in Taiwan are evaluated via
      stack sampling and analysis. Two MWIs investigated are equipped with activated
      carbon injection (ACI) and selective catalytic reduction system (SCR) as major
      PCDD/F control devices, respectively. The average PCDD/F concentrations of stack
      gases are 2.35 and 1.49 ng/N m(3), and the international toxic equivalent
      quantity (TEQ) are 0.17 and 0.043 ng TEQ/N m(3) in MWI-A and MWI-B, respectively.
      The average removal efficiency of PCDD/Fs achieved with ACI+BF (bag filters)
      reaches 95% (MWI-A) while that achieved with the WS (wet scrubber)+SCR system
      reaches 99% (MWI-B). The results obtained on gas/particulate partitioning in flue
      gases indicate that particulate-phase PCDD/Fs accounted for 27.7% and 24.7% of
      the total PCDD/F concentrations at the outlets of cyclone (CY) and electrostatic
      precipitator (EP) for MWI-A and MWI-B, respectively. But the gas/particulate
      partitioning in flue gas after PCDD/Fs control devices is quite different in two
      MWIs. This study also indicates that total 2,3,7,8-substituted PCDD/F discharges
      are 142.3 microg TEQ/ton waste for MWI-A and 98.6 microg TEQ/ton waste for MWI-B,
      respectively.

PMID- 16084976
TI  - Influence of in-tunnel environment to in-bus air quality and thermal condition in
      Hong Kong.
AB  - In this study, the potential exposure of bus commuters to significant air
      parameters (CO(2), CO and RSP) and thermal environment (air temperature and
      relative humidity) when buses traveled through tunnels in Hong Kong was
      investigated. It was found that air-conditioned buses provided a better commuting
      environment than non-air-conditioned buses. The blate increasing trend was found
      on air-conditioned buses as the in-bus air parameters concentration levels rose
      slowly throughout the traveling process. In contrast, the in-bus environment
      varied rapidly on non-air-conditioned buses as it depended on the out-bus
      environment. The measured in-bus CO concentration was 2.9 ppm on air-conditioned
      buses, while it was 4.6 ppm (even reaching the highest level at 12.0 ppm) on non
      air-conditioned buses. Considering the in-bus thermal environment, air
      conditioned buses provided thermally comfortable cabins (about 24 degrees C and
      59% of relative humidity). However, on non-air-conditioned buses, the thermal
      environment varied with the out-bus environment. The mean in-bus air temperature
      was about 34 degrees C and 66% of relative humidity, and the in-bus air
      temperature varied between 29 and 38 degrees C. Also, the lower-deck to upper
      deck air parameters concentration ratios indicated that the vertical dispersion
      of air pollutants in tunnels influenced non-air-conditioned buses as higher air
      parameters concentration levels were obtained on the lower-deck cabins.

PMID- 16084977
TI  - Soil, water, and pasture enrichment of antimony and arsenic within a coastal
      floodplain system.
AB  - Moderate levels of enrichment with environmental contaminants, such as arsenic
      (As) and antimony (Sb), have received less attention than gross contamination
      related to obvious point sources of pollution. Within the Macleay floodplain of
      north-eastern NSW it was found that approximately 90% of the floodplain is
      enriched in As and Sb, and 6-8% of the floodplain contains As and Sb levels
      greater than current Australian soil environmental investigation levels.
      Variation in surface and depth distributions indicated flood deposition of As and
      Sb across major environmental floodplain environments, with highest accumulation
      in modern swamp depositional environments. The soil enrichment was reflected by
      pasture uptake (up to 6.4 and 2.2 mg kg(-1) for As and Sb, respectively) and
      elevated surface water concentrations (up to 10 and 21 times drinking guideline
      values and 2.9 and 6.9 times freshwater trigger values for protection of 95% of
      species for As and Sb, respectively) of these metalloids. Significant
      relationships between pasture and total soil levels imply higher relative
      availability than is typical at grossly contaminated sites. Implications for
      metalloid mobility and availability in acid sulfate soil environments in the
      floodplain are discussed.

PMID- 16084978
TI  - Effect of watershed parameters on mercury distribution in different environmental
      compartments in the Mobile Alabama River Basin, USA.
AB  - Total mercury (THg) and mono-methylmercury (MeHg) levels in water, sediment, and
      largemouth bass (LMB) (Micropterus salmoides) were investigated at 52 sites
      draining contrasting land use/land cover and habitat types within the Mobile
      Alabama River Basin (MARB). Aqueous THg was positively associated with iron-rich
      suspended particles and highest in catchments impacted by agriculture. Sediment
      THg was positively associated with sediment organic mater and iron content, with
      the highest levels observed in smaller catchments influenced by wetlands,
      followed by those impacted by agriculture or mixed forest, agriculture, and
      wetlands. The lowest sediment THg levels were observed in main river channels,
      except for reaches impacted by coal mining. Sediment MeHg levels were a positive
      function of sediment THg and organic matter and aqueous nutrient levels. The
      highest levels occurred in agricultural catchments and those impacted by elevated
      sulfate levels associated with coal mining. Aqueous MeHg concentrations in main
      river channels were as high as those in smaller catchments impacted by
      agriculture or wetlands, suggesting these areas were sources to rivers. Elevated
      Hg levels in some LMB were observed across all types of land use and land cover,
      but factors such as shallow water depth, larger wetland catchment surface area,
      low aqueous potassium levels, and higher Chl a concentrations were associated
      with higher Hg burdens, particularly in the Coastal Plain province. It is
      suggested that the observed large variability in LMB Hg burdens is linked to fish
      displacement by anglers, differences in food web structure, and sediment
      biogeochemistry, with surficial sediment iron oxides buffering the flux of MeHg
      from sediments to deeper water pelagic food webs.

PMID- 16084979
TI  - First approach of a method to assess water quality for arid climate bay in the
      Gulf of California.
AB  - This work proposes a water quality model based on the pooled effects of nitrate,
      nitrite, ammonium, and orthophosphate concentration as the main causatives of
      environmental water quality changes. One of the main characteristics of the model
      is assigning an environmental weight for each variable (zeta(i)) according to
      threshold concentrations of nutrients capable of inducing water changes
      condition. The model validation demonstrated adequate sensitivity to different
      data arrangements; as observed in an arid climate bay, showing annual
      stratification resulting in a variable content in nitrogen-forms and phosphorous.
      The model can be continuously calibrated over time by adding more N and P data to
      specific nutrient functions, and tested on sites with high NO(3), NO(2) or NH(4)
      concentrations.

PMID- 16084980
TI  - Use of mineral magnetic concentration data as a particle size proxy: a case study
      using marine, estuarine and fluvial sediments in the Carmarthen Bay area, South
      Wales, U.K.
AB  - Compositional (non-magnetic) data can correlate strongly with particle size,
      which deems it appropriate as a particle size proxy and, therefore, a reliable
      means of normalising analytical data for particle size effects. Previous studies
      suggest magnetic concentration parameters represent an alternative means of
      normalising for these effects and, given the speed, low-cost and sensitivity of
      the measurements may, therefore, offer some advantages over other compositional
      signals. In this work, contemporary sediments from a range of depositional
      environments have been analysed with regard to their mineral magnetic
      concentration and textural characteristics, to observe if the strength and nature
      of the relationship identified in previous studies is universal. Our data shows
      magnetic parameters (chi(LF), chi(ARM) and SIRM) possess contrasting
      relationships with standard textural parameters for sediment samples collected
      from marine (Carmarthen Bay), estuarine (Gwendraeth Estuary) and fluvial (Rivers
      Gwendraeth Fach and Gwendraeth Fawr) settings. Magnetic concentrations of
      sediments from both the marine and estuarine environments are highly influenced
      by the magnetic contribution of finer particle sizes; Gwendraeth Fawr River
      sediments are influenced by the magnetic contribution of coarser particle sizes,
      while sediments from the Gwendraeth Fach River are not influenced significantly
      by any variations in textural properties. These results indicate mineral magnetic
      measurements have considerable potential as a particle size proxy for particular
      sedimentary environments, which in certain instances could be useful for
      geochemical, sediment transport, and sediment provenance studies. However, the
      data also highlight the importance of fully determining the nature of the
      relationship between sediment particle size and magnetic properties before
      applying mineral magnetic data as a particle size proxy.

PMID- 16084981
TI  - Assessing contamination levels of Laguna Lake sediments (Philippines) using a
      contact assay with zebrafish (Danio rerio) embryos.
AB  - The present study investigated the suitability of a sediment contact assay using
      zebrafish (Danio rerio) embryos to evaluate the degree of lake sediment
      contamination. As endpoints, developmental parameters (mortality, abnormality,
      heart rate, and hatching rate) as well as stress protein responses (hsp 70
      levels) in the developing embryos were recorded during a 96-h exposure.
      Fertilized zebrafish eggs were exposed to both the whole as well as organic
      extract concentrations prepared from collected sediments from 5 sites along
      Laguna Lake, Philippines. Compared to whole sediment exposure, more severe
      embryotoxic and teratogenic responses were elicited in embryos exposed to organic
      extracts. However, since whole sediment-exposed embryos also revealed significant
      developmental defects, this exposure phase served as the more realistic exposure
      scenario in our study. Weak to strong upregulation of hsp 70 levels was also
      registered among embryos exposed to both whole sediments and organic extracts.
      The observed embryotoxic and proteotoxic responses by zebrafish embryos to Laguna
      Lake sediment exposures were discussed in relation to the analyzed contaminants
      in the sediments (heavy metals, PAHs (perylene), solvent). Overall, the present
      study points out that the sediment contact assay with zebrafish embryos offers a
      practicable and highly sensitive bioassay for the general assessment of sediment
      toxicity.

PMID- 16084982
TI  - A methodology to estimate benzene concentrations in a town through a traffic
      model.
AB  - In this work an approach is presented that describes the changes of benzene
      concentration in the air, in relation with the special traffic characteristics of
      a road. The dominant input parameters of the model are traffic density and the
      vehicle's type distribution according to seven main categories characterized by
      different emission factors. The dispersion approach used is a semi-empirical
      relationship that apart from emission rates requires also wind speed and the
      direction, as well as the geometrical characteristics of the road. The
      methodology was validated for Ioannina, a Greek medium sized town with special
      traffic and geographic characteristics presenting high atmospheric pollution
      values. It is found that the benzene concentrations estimated by the methodology
      are in a very good agreement with the measurements.

PMID- 16084983
TI  - Anthropogenic impacts on mercury concentrations and nitrogen and carbon isotope
      ratios in fish muscle tissue of the Truckee River watershed, Nevada, USA.
AB  - The lower Truckee River originates at Lake Tahoe, California/Nevada (NV), USA and
      ends in the terminal water body, Pyramid Lake, NV. The river has minimal
      anthropogenic inputs of contaminants until it encounters the cities of Reno and
      Sparks, NV, and receives inflows from Steamboat Creek (SBC). SBC originates at
      Washoe Lake, NV, where there were approximately six mills that used mercury for
      gold and silver amalgamation in the late 1800s. Since then, mercury has been
      distributed down the creek to the Truckee River. In addition, SBC receives
      agricultural and urban nonpoint source pollution, and treated effluent from the
      Reno-Sparks water reclamation facility. Fish muscle tissue was collected from
      different species in SBC and the Truckee River and analyzed for mercury and
      stable isotopes. Nitrogen (delta(15)N) and carbon (delta(13)C) isotopic values in
      these tissues provide insight as to fish food resources and help to explain their
      relative Hg concentrations. Mercury concentrations, and delta(15)N and delta(13)C
      values in fish muscle from the Truckee River, collected below the SBC confluence,
      were significantly different than that found in fish collected upstream. Mercury
      concentrations in fish tissue collected below the confluence for all but three
      fish sampled were significantly greater (0.1 to 0.65 microg/g wet wt.) than that
      measured in the tissue collected above the confluence (0.02 to 0.1 microg/g).
      Delta(15)N and delta(13)C isotopic values of fish muscle collected from the river
      below the confluence were higher and lower, respectively, than that measured in
      fish collected up river, most likely reflecting wastewater inputs. The impact of
      SBC inputs on muscle tissue isotope values declined down river whereas the impact
      due to Hg inputs showed the opposite trend.

PMID- 16084984
TI  - Neopterin concentrations in blood donors differ between AB0 blood group
      phenotypes.
AB  - OBJECTIVES: Neopterin is produced by human monocyte-derived macrophages upon
      stimulation with interferon-gamma and is therefore a sensitive indicator for
      cellular immune activation. Common factors like age, diastolic blood pressure,
      body mass index, or smoking habits were found to be associated with neopterin
      concentrations in humans. DESIGN AND METHODS: In order to find possible genetic
      determinants which might influence neopterin production, we investigated 8288
      consecutive blood donors after exclusion of samples suspicious of infections.
      RESULTS: Donors with blood group phenotype 0 had moderately, but significantly (P
      < 0.0001) higher neopterin concentrations (mean +/- SD: 6.94 +/- 1.52 nmol/L)
      than those with phenotype A (6.75 +/- 1.50 nmol/L), phenotype B (6.73 +/- 1.48
      nmol/L), and phenotype AB (6.68 +/- 1.57 nmol/L). CONCLUSIONS: Neopterin levels
      are higher in donors with blood group phenotype 0 than in other phenotypes. Data
      point to a genetic background of different neopterin concentrations. However,
      alterations of neopterin levels were much less expressed than the changes known
      to occur during diseases with an activated immune response.

PMID- 16084985
TI  - A proactive community laboratory and the management of diabetes.

PMID- 16085008
TI  - "Gap guidance" of fibroblasts and epithelial cells by discontinuous edged
      surfaces.
AB  - Cell adhesion, shape, and directed migration are some of the fundamental
      processes underlying tissue development and organization. The setting of
      geometric limits on cellular behavior has led to the hypothesis that a continuous
      edge is required to elongate a cell and guide its direction of movement. The aim
      of this study was to examine the validity of this hypothesis by examining the
      response of human gingival fibroblasts and periodontal ligament epithelial cells,
      to microfabricated surfaces that incorporate discontinuous edges. Cell response
      was assessed through spreading, morphology, cytoskeletal organization, and time
      lapse microscopy, on substrata with a pattern of repeated open boxes with gaps at
      the corners. Fibroblasts attached and spread within 6 h, adopting either a
      square, triangular, or diagonally elongated morphology. Epithelial cells took
      longer to adhere, but were observed to adopt morphologies similar to those of the
      fibroblasts. Addition of colcemid or cytochalasin-D attenuated the orientation
      and alignment of both fibroblasts and epithelial cells. Fibroblasts and
      epithelial cell migration was guided diagonally in their movement through gaps in
      the square pattern, demonstrating that a continuous edge is not a prerequisite
      for guided cell migration.

PMID- 16085009
TI  - Focus on molecules: cellular retinaldehyde-binding protein (CRALBP).

PMID- 16085011
TI  - A comparative review of classification systems in myelodysplastic syndromes
      (MDS).
AB  - Reliable classification and prognostic scoring systems for myelodysplastic
      syndromes (MDS) are needed to facilitate medically appropriate treatment and
      management decisions. The French-American-British (FAB) classification scheme for
      MDS was described in 1982 and has become the reference standard for subsequent
      MDS classification schemes. The FAB classification system divides MDS into five
      subgroups, based mainly on morphologic criteria and the percentage of myeloblasts
      in bone marrow (BM). More recently, the increasing availability of BM
      cytogenetics, immunologic markers, and molecular genetics has provided important
      information for staging, prognosis, and treatment of MDS. A World Health
      Organization panel incorporated this new diagnostic information into a revised
      classification system that modified the FAB criteria while retaining most of its
      basic features. The major changes included the creation of additional categories
      (eg, 5q- syndrome), distinction of unilineage from multilineage dysplasias in the
      refractory anemias, and subdivision of the heterogeneous refractory anemias with
      excess blasts into two categories based on BM blast percentage. Additionally,
      some MDS subtypes were removed or merged with other myeloid disorders into newly
      created categories. In independent validations, the World Health Organization
      revisions were shown to provide more-homogeneous subgroups of patients and
      greater prognostic power compared with the FAB system, although controversies
      remain. The International Prognostic Scoring System combines blast percentage,
      karyotype, and number of cytopenias to generate a scoring system that reliably
      estimates survival and risk of transformation to acute myeloid leukemia for
      patients with MDS. This universally accepted scoring system is often combined
      with FAB or World Health Organization morphologic criteria to provide a more
      complete clinical picture and the most accurate prognostic assessment possible.
      As more is learned about the pathogenesis of MDS at the molecular level, it is
      anticipated that these classification and scoring systems will continue to evolve
      to incorporate the new information.

PMID- 16085012
TI  - Response assessments in low-risk and high-risk myelodysplastic syndromes (MDS).
AB  - The myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic
      disorders that differ with regard to etiology, pathologic and clinical features,
      treatment, and outcomes. MDS are chronic, progressive diseases that may be
      broadly categorized into early phase ("low-risk") and late-phase ("high-risk")
      groups based on prognostic criteria and the differential pathologic and
      cytogenetic features that drive the MDS phenotype in these disease phases.
      Consequently, the goals for treatment and management options also differ for low
      risk MDS compared with high-risk MDS. Alleviation of disease-related
      complications, including transfusion requirements, and hematologic improvement
      are key treatment goals in low-risk MDS. In contrast, altering the natural
      history of disease, including improvements in overall survival and progression
      free survival, are the most important treatment goals in high-risk MDS. To
      address the heterogeneity of MDS in patient populations enrolled in clinical
      trials and to resolve problems resulting from variability in the quality and
      quantity of responses to treatment, the International Working Group has developed
      standardized response criteria for MDS that are relevant for both low-risk and
      high-risk categories. The application of the standardized International Working
      Group response criteria in clinical trials is enabling the comparison of results
      from various clinical trials in MDS. Furthermore, the International Working Group
      response criteria provide an important framework for clinical development of new
      treatments options that may be particularly appropriate for specific MDS subsets.

PMID- 16085013
TI  - Treatment strategies and issues in low/intermediate-1-risk myelodysplastic
      syndrome (MDS) patients.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of progressive bone
      marrow neoplastic disorders associated with increased risk for transformation to
      acute leukemia. Hallmarks of MDS are peripheral blood cytopenias (especially
      anemia), frequently with hypercellular bone marrow, and dysplastic changes in one
      or more hematopoietic lineages. The wide variation in clinical presentation has
      confounded treatment strategies and hindered the development of new therapies.
      However, improved classification and prognostic systems are providing a more
      refined stratification of patients, helping to guide treatment and management
      decisions as well as to appropriately select patients for clinical trials.
      Patients with International Prognostic Scoring System classifications of low- and
      intermediate-1 (Low/Int-1) risk are considered to have "low-risk" MDS. These
      patients are primarily treated with low-intensity supportive care, especially red
      blood cell transfusions, to treat their symptoms and maintain their quality of
      life. In small subsets of Low/Int-1-risk patients with MDS, hematopoietic
      cytokines or antithymocyte globulin may reduce transfusion requirements. The
      drawbacks to these treatments are high failure rates, even with improved
      predictive models, and the high cost of cytokines. Regardless of risk category, a
      patient's age and existing comorbidities must be factored into treatment
      decisions. It is anticipated that trials with new and investigational agents may
      soon provide definitive treatments for patients with Low/Int-1-risk MDS when used
      alone or in conjunction with supportive measures.

PMID- 16085014
TI  - IMiDs: a novel class of immunomodulators.
AB  - IMiDs are structural and functional analogues of thalidomide that represent a
      promising new class of immunomodulators for treatment of a variety of
      inflammatory, autoimmune, and neoplastic diseases. The discovery of the
      antiangiogenic and T-cell co-stimulatory functions of IMiD compounds has led to
      the investigation of these agents for treatment of hematologic neoplasms such as
      multiple myeloma and myelodysplastic syndromes, as well as certain solid tumors.
      The second-generation IMiDs, such as lenalidomide and CC-4047, exhibited a
      greatly enhanced potency for immunomodulation and antiangiogenesis in nonclinical
      studies when compared with the parent compound, thalidomide. In clinical studies,
      the IMiDs appear to have reduced sedative and neurotoxicity effects, which are
      often associated with long-term thalidomide dosing. The precise mechanism of
      action of IMiDs in the treatment of specific diseases is not entirely clear and
      may differ for various diseases depending on their underlying pathobiologies.
      Although IMiDs have similar effects on inflammatory cytokine secretion, T-cell
      modulation, angiogenesis, and expression of adhesion molecules, each IMiD has a
      unique potency profile for these activities, which may ultimately indicate
      selective applicability of specific IMiDs for distinct diseases and conditions.
      Clinical trials of lenalidomide, the primary second-generation IMiD, have shown
      clinical benefits in both myelodysplastic syndrome and multiple myeloma and a
      better safety profile than that of thalidomide, with no evidence of
      teratogenicity. It is anticipated that lenalidomide and other IMiD compounds will
      become important alternatives to thalidomide because of their more potent anti
      inflammatory and anticancer properties, as well as their improved side-effect
      profiles.

PMID- 16085015
TI  - Emerging data on IMiDs in the treatment of myelodysplastic syndromes (MDS).
AB  - Myelodysplastic syndromes (MDS) encompass a spectrum of clinically diverse
      hematopoietic stem cell malignancies for which there are few treatment options.
      These disorders display remarkable heterogeneity in their hematologic and
      pathologic features, with a wide-ranging natural history. Complex interactions
      between the affected clone and the bone marrow microenvironment drive the
      pathogenesis and progression of MDS, resulting in ineffective hematopoiesis,
      blast accumulation, and a variable predisposition for progression to acute
      leukemia. For early stage, lower-risk patients with MDS, the mainstay of therapy
      is supportive care, especially red blood cell transfusions, to alleviate the
      symptoms of anemia. However, these interventions do not target the underlying
      pathobiology of disease and have questionable impact on the natural disease
      course. Dysregulated inflammatory, apoptotic, and angiogenic cytokines play major
      roles in the pathobiology of MDS and represent attractive therapeutic targets.
      Lenalidomide is an orally bioavailable analogue of thalidomide with more potent
      immunomodulatory, antiangiogenic, and antitumor activities than the parent
      compound and with a better safety profile. In nonclinical studies, the effects of
      lenalidomide include potentiation of clonogenic response to erythropoietin,
      activation of integrin-mediated adhesion, cell cycle arrest, sensitization to
      apoptotic signals, and abrogation of cellular response to receptor-initiated
      trophic signals. These effects have the potential to impact survival and
      apoptosis of erythropoietic progenitor cells and their progeny. Data from
      clinical trials of lenalidomide in MDS have shown erythropoietic- and cytogenetic
      remitting activities that frequently result in transfusion independence,
      particularly in patients with 5q- deletion and lower-risk MDS. Decreases in
      microvessel density in bone marrow specimens from responding patients provide
      supportive evidence of an antiangiogenic effect in MDS. Adverse effects, most
      commonly myelosuppression, are generally manageable with dose reduction and
      growth factor support. Multicenter phase II and III studies are under way to
      further assess the erythroid and cytogenetic response rates in distinct subtypes
      of MDS, including 5q- deletion, and to optimize its clinical application.

PMID- 16085016
TI  - Cortical modulation of neuronal activity in the cat's lateral geniculate and
      perigeniculate nuclei.
AB  - The cortico-thalamic influence on spontaneous and visually evoked activity of
      single cells in the dorsal lateral geniculate (LGN) and perigeniculate (PGN)
      nuclei were examined in unanesthetized cats with pretrigeminal brainstem
      transections by means of reversible cooling of cortical areas 17 and 18. The
      spatio-temporal characteristic of cells' RFs was tested with light spot randomly
      presented at different points along the receptive field axis. The cessation of
      cortical input decreased spontaneous activity of most of the LGN cells (64%; as
      compared to 36% with increased background firing). Similarly, their visually
      evoked responses were reduced (70% cells; compared to 24% with increased
      response) and extent of central excitatory domains diminished. In contrast, the
      majority of PGN neurons increased their spontaneous activity (62%; compared to
      38% with decreased firing rate). Cortical cooling resulted also in a decrease of
      the ON and OFF central responses of most PGN cells (55%; as compared to 20% with
      increased responses). The described effects were more pronounced within the
      population of cells in X than in Y pathway. Although the removal of descending
      cortical excitation disturbed the balance of activity within the network of
      thalamic cells the gain of the geniculate relay was preserved. We conclude that
      the main role exerted by the cortico-thalamic pathway serves facilitation of the
      ascending retino-cortical flow of visual information at the level of lateral
      geniculate nucleus.

PMID- 16085017
TI  - Apoptotic signals within the basal forebrain cholinergic neurons in Alzheimer's
      disease.
AB  - A relatively early and substantial loss of basal forebrain cholinergic neurons is
      a constant feature of Alzheimer's disease (AD). However, the mechanisms that
      contribute to the selective vulnerability of these neurons are not fully
      delineated. In the present series of experiments, we determined the possible
      contribution of apoptotic processes and other pathologic cascades to the
      degeneration of the cholinergic neurons of the nucleus basalis of Meynert (NBM)
      in AD. In contrast to neurons in the frontal cortex which showed prominent DNA
      fragmentation as detected by the TUNEL method, no DNA fragmentation was observed
      within the NBM in any of the AD or normal brains. Similarly, immunoreactivity for
      the apoptotic signals Fas, Fas-ligand, Bax, Bcl-x, caspase-8, caspase-9 and
      caspase-3 was absent from the NBM of AD and control brains. In contrast, a
      substantial subpopulation of cholinergic neurons within the NBM in AD displayed
      prominent immunoreactivity for the apoptotic signal Fas-associated death domain
      (FADD) in the form of tangles. FADD immunoreactivity was also present in
      dystrophic neurites. FADD-positive tangle-like structures were localized in
      neurons which contained immunoreactivity for the cholinergic marker choline
      acetyltransferase (ChAT) and the low affinity neurotrophin receptor p75NTR. While
      many of the NBM cholinergic neurons in control brains contained immunoreactivity
      for the calcium binding protein calbindin-D28K (CB), the NBM neurons in AD
      displayed a substantial loss of CB immunoreactivity. Importantly, most of FADD
      immunoreactive cholinergic neurons were devoid of CB immunoreactivity, and,
      conversely, most CB-positive cholinergic neurons had no FADD immunoreactivity.
      FADD immunoreactivity within the basal forebrain was colocalized with
      phosphorylated tau immunoreactive tangles and dystrophic neurites. In contrast,
      FADD immunoreactivity did not appear to be related to the primarily diffuse
      amyloid-beta deposits intermingled between cholinergic neurons in AD NBM.
      Finally, many CD68-positive microglia were observed surrounding the NBM
      cholinergic neurons in AD. In conclusion, the findings of the present study
      indicate that, while the FADD apoptotic signaling pathway may be triggered within
      the basal forebrain cholinergic neurons in AD, the apoptotic cascade is most
      likely aborted as no DNA fragmentation was detected and the executioner caspase-3
      was not up-regulated within these neurons. The findings also suggest possible
      relationships between loss of CB, FADD expression and phosphorylation of tau
      within the basal forebrain cholinergic neurons in AD.

PMID- 16085019
TI  - Maternal infection and adverse fetal and neonatal outcomes.
AB  - Adverse pregnancy outcomes can follow direct placental, fetal, or neonatal
      infection, or preterm birth associated with vaginal, cervical, intrauterine, or
      even nonpelvic infections. These latter infections appear to be associated with
      the majority of very early preterm births, and may explain some of the long-term
      neurologic damage associated with preterm birth. Bacterial vaginosis and its
      associated intrauterine infections likely contribute far more to the overall
      burden of adverse pregnancy outcomes than the more classical perinatal infections
      such as rubella and syphilis.

PMID- 16085020
TI  - Pathophysiology of preterm birth: emerging concepts of maternal infection.
AB  - Preterm birth remains a significant health concern. Maternal reproductive
      infections such as bacterial vaginosis pose increased risk for preterm birth,
      although treatment of bacterial vaginosis has not proven to be universally
      effective in preterm birth prevention. Maternal oral infection such as clinical
      periodontal disease has also been identified as a risk factor for preterm birth,
      and pilot data suggest that oral treatment interventions undertaken during
      pregnancy may reduce preterm birth risk.

PMID- 16085021
TI  - Preterm labor, preterm premature rupture of membranes, and chorioamnionitis.
AB  - In this article, the author reviews the etiology and biochemical links between
      infection and preterm birth, the problem of preterm birth, and the management of
      infection-related risks of preterm birth. The management section reviews current
      opinions regarding prophylactic antibiotic therapy in the prevention of preterm
      birth, adjunctive antibiotic therapy in the treatment of preterm labor with and
      without rupture of membranes, and antibiotic therapy of intra-amniotic infection
      (clinical chorioamnionitis, IAI). Finally, the article reviews the risk of
      neurodevelopmental handicap potentially associated with IAI.

PMID- 16085022
TI  - Prevention of neonatal sepsis.
AB  - Neonatal sepsis is a leading infectious cause of infant mortality. While use of
      intrapartum antibiotic prophylaxis in the United States has led to dramatic
      declines in perinatal sepsis caused by the bacteria group B streptococcus,
      interventions to prevent perinatal sepsis due to other causes have not yet been
      clearly defined. This article synthesizes information on neonatal sepsis disease
      burden, trends, and risk factors and reviews current and potential approaches to
      neonatal sepsis prevention.

PMID- 16085023
TI  - Bacterial vaginosis in pregnancy: diagnosis, screening, and management.
AB  - Bacterial vaginosis is the most common lower genital tract infection among women
      of reproductive age. It has been associated with a number of significant
      obstetric and gynecologic complications, such as preterm labor and delivery,
      preterm premature rupture of membranes, spontaneous abortion, chorioamnionitis,
      postpartum endometritis, postcesarean delivery wound infections, postsurgical
      infections, and subclinical pelvic inflammatory disease. This article focuses on
      bacterial vaginosis in pregnancy, and discusses approaches to diagnosis,
      screening, and management.

PMID- 16085024
TI  - Treatment of sexually transmitted infections in pregnancy.
AB  - Sexually transmitted infections remain a major public health concern in the
      United States. An estimated 19 million infections occur each year. The economic
      burden imposed by sexually transmitted infections is impressive: direct medical
      costs have been estimated as high as 15.5 billion US dollars annually. Sexually
      transmitted infections are relatively common during pregnancy, especially in
      indigent, urban populations. Education, screening, treatment, and prevention are
      important components of prenatal care for women at increased risk for these
      infections. Treatment of these sexually transmitted infections is clearly
      associated with improved pregnancy outcome and reductions in perinatal mortality.

PMID- 16085025
TI  - Herpes simplex virus in pregnancy: new concepts in prevention and management.
AB  - Genital herpes simplex virus (HSV) infection is one of the most common viral
      sexually transmitted diseases in the United States. It is estimated that 45
      million adolescents and adults are infected with genital HSV. Most genital herpes
      infections in the United States are caused by HSV type 2 (HSV-2), and 25% to 30%
      of women of reproductive age have HSV-2 antibodies. What is more striking is that
      genital herpes is frequently under-recognized, and that only 5% to 10% of these
      women have a history of genital herpes. Because such a small percentage of women
      are aware of being infected with HSV, the risk of maternal transmission of this
      virus to the fetus or newborn is a significant health issue.

PMID- 16085026
TI  - Human herpes viruses in pregnancy: cytomegalovirus, Epstein-Barr virus, and
      varicella zoster virus.
AB  - Viruses of the human herpesvirus family can have profound effects on pregnancy.
      Primary maternal infection with cytomegalovirus (CMV) and varicella during
      pregnancy has been associated with fetal abnormalities and neonatal disease.
      Public awareness of the role of cytomegalovirus in the etiology of developmental
      disorders and chronic disabilities needs to increase. With time, we may see new
      interventions for treatment of infected pregnant women and prevention of long
      term effects. Attention must be focused on development of a safe and effective
      vaccine. With the introduction of an efficacious varicella vaccine, the rate of
      varicella in pregnancy is expected to decrease dramatically. Physicians caring
      for women have the opportunity to prevent the complications of varicella by
      identifying and vaccinating susceptible women.

PMID- 16085027
TI  - Diagnosis and management of human parvovirus B19 infection.
AB  - Parvovirus B19 is a common infection in children occurring in winter and spring
      months that can affect pregnant women and their unborn fetuses. Adverse fetal
      sequelae may include red blood cell aplasia due to bone marrow suppression,
      anemia, myocarditis, nonimmune hydrops, and fetal death. Fortunately, several
      noninvasive testing schemes are available to assess the fetus, and invasive
      testing is reserved for fetuses with marked anemia.

PMID- 16085028
TI  - Diagnosis and management of toxoplasmosis.
AB  - This article discusses the diagnosis and management of toxoplasmosis. Congenital
      toxoplasmosis continues to be a tragic outcome of a preventable and treatable
      infection. Education of patients, physicians and health policy makers on the
      primary and secondary preventive measures of the disease, and their execution,
      will undoubtedly result in lower incidence, morbidity, and mortality rates from
      congenital disease due to Toxoplasma gondii.

PMID- 16085029
TI  - Influenza and pneumonia in pregnancy.
AB  - Influenza is a significant cause of morbidity and mortality from febrile
      respiratory illness worldwide. Influenza in pregnant women has historically been
      associated with a higher rate of morbidity and mortality. Pneumonia is the sixth
      leading cause of death in the United States, and it is the number one cause of
      death from an infectious disease. Although pregnant women do not get pneumonia
      more often than nonpregnant women, it can result in greater morbidity and
      mortality because of the physiologic adaptations of pregnancy. Pregnant patients
      who have either of these conditions require a higher level of surveillance and
      intervention.

PMID- 16085030
TI  - Tuberculosis in pregnancy.
AB  - There were approximately 2 million deaths worldwide from tuberculosis in 1997,
      98% of them in developing countries. Factors implicated in the resurgence of
      tuberculosis in the United States in the late 80s and early 90s included
      increased immigration from countries with high prevalence, HIV infection,
      emergence of resistant strains, poverty, homelessness, drug abuse, and a decline
      in tuberculosis-related health services. With better control programs, cases
      began to decrease in 1993. In 1998, 18,361 cases of tuberculosis (6.8 per 100,000
      population) were reported to the US Centers for Disease Control and Prevention
      (CDC), a 31% decrease from 1992. Pregnancy is not thought to change the course of
      tuberculosis; however, tuberculosis poses a risk to the pregnant woman and her
      fetus.

PMID- 16085031
TI  - Urinary tract infections in pregnancy.
AB  - Urinary tract infections occur commonly in pregnancy. Bacterial colonization may
      occur in the lower and upper urinary tract, and is facilitated by the normal
      physiologic changes of pregnancy. Asymptomatic bacteriuria, cystitis, and
      pyelonephritis each pose a serious threat to the mother and fetus. Optimal
      treatment regimens and preventative strategies continue to be investigated.

PMID- 16085032
TI  - Emerging infections and pregnancy: West Nile virus, monkeypox, severe acute
      respiratory syndrome, and bioterrorism.
AB  - As new infectious diseases, such as West Nile virus, monkeypox, and severe acute
      respiratory syndrome (SARS) are recognized in the United States, there are
      critical questions about how these infectious diseases will affect pregnant women
      and their infants. In addition, the implications of bioterrorist attacks for
      exposed pregnant women need to be considered. In this article, the authors
      address the following questions for a number of infectious disease threats: (1)
      does pregnancy affect the clinical course of these novel infectious diseases?,
      (2) what are the implications for prophylaxis and treatment of exposed or
      infected pregnant women?, and (3) are these novel infectious diseases transmitted
      during pregnancy, labor and delivery, or breastfeeding?

PMID- 16085033
TI  - Epidural analgesia for labor pain and its relationship to fever.
AB  - The association between labor epidural and maternal fever is well established.
      The direct effect of epidural on maternal temperature appears due to its
      interference with heat dissipation and rarely results in overt fever. This effect
      is unlikely to adversely affect the fetus, the majority of women in labor do not
      appear to be at risk, and the full ramification of the fever is not yet well
      understood. Thus it seems unreasonable to avoid labor epidurals due to the risk
      of fever. Epidural analgesia remains one of the most effective forms of pain
      relief in labor and is a reasonable option for most women.

PMID- 16085034
TI  - The use of radiographic modalities to diagnose infection in pregnancy.
AB  - The usefulness of sonography, plain film, CT, and MRI in diagnosing infections in
      pregnancy is discussed. Imaging modality choices for specific clinical
      indications in pregnancy are reviewed. The overall safety of most techniques in
      pregnancy is emphasized.

PMID- 16085035
TI  - Postpartum endometritis.
AB  - Postpartum endometritis or a surgical site infection should be suspected if the
      patient develops an elevated oral temperature, 100.4 degrees F or higher, with an
      associated tachycardia following the procedure. A tachycardia paralleling the
      temperature strongly indicates infection. A thorough examination should be
      performed. Patients failing to respond to initial antibiotic therapy should be
      thoroughly evaluated for the possible emergence of a resistant bacterium or the
      development of an abscess or septic pelvic thrombosis. Antibiotic therapy should
      be continued until the patient is afebrile for 24 to 48 hours, the white blood
      cell count returns to normal, and the patient is tolerating oral liquids and
      solids, and ambulating without difficulty.

PMID- 16085036
TI  - Trypanosoma cruzi: chemotherapeutic effects of clomipramine in mice infected with
      an isolate obtained from an endemic area.
AB  - The susceptibility of Trypanosoma cruzi strains to nifurtimox and benznidazole
      has been investigated and resistant strains have been described. Some tricyclic
      drugs are lethal for trypomastigote and epimastigote forms of T. cruzi (Tulahuen
      strain) and prevent the disease in mice. We investigated whether clomipramine, a
      tricyclic antidepressant drug with anti-trypanothione reductase and anti
      calmodulin effects, could be effective in treating Albino Swiss mice infected
      with trypomastigotes of a new T. cruzi isolate from a chronic patient from an
      endemic area of Argentina in two different treatment schedules. Both treatment
      schedules were effective in reducing electrocardiographic changes and preventing
      myocardial structural damage. The cardiac beta-receptors low affinity was
      compensated for by an increment in their density. This probably maintained
      cardiac function since 70% of the mice survived for more than 2 years even though
      anti-cruzipain titers remained high. These results demonstrate that clomipramine,
      clinically used as a neuroleptic, could be a promising trypanocidal agent for the
      treatment of Chagas' disease.

PMID- 16085037
TI  - The current molecular phylogeny of Eutherian mammals challenges previous
      interpretations of placental evolution.
AB  - Based on histology, the placentae of eutherians are currently grouped in
      epitheliochorial, endotheliochorial and haemochorial placentae. In a haeckelian
      sense, the epitheliochorial contact with marked histiotrophic feeding by uterine
      milk is generally considered as primitive, especially since similar contacts
      exist in Marsupials. In contrast, the more intimate endotheliochorial and
      haemochorial contact, facilitating haemotrophic nutrition, is interpreted as a
      derived state. A cladistic analysis based on the phylogenetic relationships
      established by molecular analyses reveals that the basic clades are all
      characterized by an endotheliochorial or haemochorial placenta, and that the
      epitheliochorial placenta evolved at least three times in a convergent manner.
      This evolution may be explained by the fact that the epitheliochorial placenta in
      eutherians is more efficient in nutritional transfer (flow rate by exchange
      surface). Moreover, this arrangement may confer an advantage to the mother who
      can probably reduce the degree of manipulation by a genetically imprinted embryo.

PMID- 16085038
TI  - Placentation in an American mole, Scalopus aquaticus.
AB  - In 1938 Mossman reported that epitheliochorial placentation occurred in an
      insectivore, the Eastern mole. This led to a radical change in his thinking about
      placental evolution, yet 40 years would pass before the appearance of a
      definitive description. Unpublished papers in the Mossman Collection at the
      University of Wisconsin Zoological Museum tell a fascinating story about this
      delay. The Scalopus material was studied by Mossman's graduate student, M.R.N.
      Prasad, who concluded that the placenta was initially endotheliochorial and that
      subsequent re-epithelialization of the uterus led to the definitive
      epitheliochorial condition. Mossman withheld publication of these findings
      pending electron microscopic studies. The definitive publication described the
      ultrastructure of the interhaemal region. Although based on a single specimen,
      this seemed to justify the conclusion that an epitheliochorial condition was
      maintained throughout gestation. These findings are discussed in relation to
      subsequent work on the European mole and current thinking about placental
      evolution.

PMID- 16085039
TI  - Evaluation of housekeeping genes in placental comparative expression studies.
AB  - Preeclampsia and diabetes are complications of pregnancy that contribute to
      maternal and perinatal mortality worldwide. Results emerging from molecular
      studies of placentae may elucidate etiologically important genomic alterations.
      Appropriate application of real time reverse transcription (RT) PCR in
      comparative gene expression studies requires endogenous housekeeping genes to
      normalize between sample variations. Ideal housekeeping genes must have stable
      tissue expression, but few have been specifically studied in the placenta. We
      sought to identify candidate control genes by analyzing seven functionally
      distinct housekeeping genes (B2M, GAPDH, HMBS, HPRT, SDHA, TBP, YWHAZ) for their
      expression stability and level in the placenta. mRNA isolated from 20 placentae
      was analyzed for gene expression using RT-PCR. Expression stability (M) was
      assessed using normalization strategies previously used for other tissues. TBP
      and SDHA were the most stable, with an average expression stability of M = 0.43,
      followed by YWHAZ (M = 0.44) > HPRT (M = 0.53) > HMBS (M = 0.57) > GAPDH (M =
      0.61) > B2M (M = 0.69). The genes tested ranged in abundance, with an
      approximately 300-fold increase from the lowest (HMBS) to the highest (B2M). By
      using TBP, SDHA and YWHAZ, with greater expression stability than those
      housekeeping genes commonly used in placenta studies, gene expression profile
      comparisons will have more sensitivity and specificity.

PMID- 16085040
TI  - Characterisation of long term cat placental explant cultures: uptake of taurine
      by system beta.
AB  - Dietary taurine is essential for cats and deficiency during pregnancy may lead to
      abortion, growth restriction or impaired neurological function of kittens. We
      previously described Na(+)- and Cl(-)-dependent taurine transport by system beta
      in fragments of freshly isolated cat placenta [Champion EE, Bailey SJ, Glazier
      JD, Jones CJP, Mann SJ, Rawlings JM, et al. Taurine uptake into cat placental
      tissue fragments. Placenta 2001;22:A.42]. Here we evaluate long term culture of
      cat placental explants as a model for the future study of chronic nutrient
      regulation of amino acid transport in this species. The cat placental explants
      displayed (i) Na(+)-dependent [(3)H]taurine uptake and (ii) taurine transporter
      protein on day 7 of culture, as observed in fresh cat placental fragments. The
      explants had preserved the ability to secrete PGF(2alpha) hormone until day 11 of
      culture and remained morphologically largely intact until day 7 of culture. This
      model of placental explant culture will provide an important in vitro method for
      the study of chronic regulation of amino acid transport in the cat.

PMID- 16085041
TI  - Interaction of Jar choriocarcinoma cells with endothelial cell monolayers.
AB  - During human pregnancy the uterine spiral arteries are invaded by placental
      trophoblasts which replace the endothelial cells that line the non-pregnant
      spiral arteries and transform these vessels into large-bore conduits enabling
      adequate perfusion of the placenta with maternal blood. Failure of this process
      may predispose to preeclampsia and fetal growth restriction [Brosens I, Robertson
      WB, Dixon HG. The physiological response of the vessels of the placental bed to
      normal pregnancy. Journal of Pathology and Bacteriology 1967;93:569-79; Khong TY,
      De Wolf F, Robertson WB, Brosens I. Inadequate maternal vascular response to
      placentation in pregnancies complicated by pre-eclampsia and by small-for
      gestational age infants. British Journal of Obstetrics and Gynaecology
      1986;93:1049-59]. There is a paucity of data on the role of maternal endothelial
      cells in this process. In this study we investigated the cellular interactions
      between trophoblast-derived Jar cells and endothelial cells (HUVECs and HMEC-1).
      The effect of coculturing Jar cells with endothelial cell monolayers was
      determined by confocal microscopy, DNA fragmentation assay and flow cytometry. We
      demonstrated that Jar cells migrate into focal areas in endothelial cell
      monolayers, where they induce endothelial cell death and, then phagocytose the
      dead endothelial cells. Our results suggest that endothelial cells may not simply
      be passive targets for invading trophoblasts during the remodeling of the spiral
      arteries.

PMID- 16085042
TI  - Localisation of glucose transport in the ruminant placenta: implications for
      sequential use of transporter isoforms.
AB  - The facilitative glucose transporters 1 and 3 are the major routes for glucose
      transport across placental membranes. Using light and electron microscope
      immunocytochemistry on acrylic sections this study shows a similar pattern of
      expression from mid to late pregnancy in all four ruminants examined [cow, deer,
      ewe and goat]. GT1 and GT3 are localised on different membrane layers of the
      synepitheliochorial placental barrier and glucose must utilise both isoforms
      sequentially to pass from the maternal to fetal circulations. It is suggested
      that this arrangement is designed to support the high glucose utilisation by the
      multilayered placenta in the ruminant.

PMID- 16085043
TI  - Equilibrative nucleoside transporter 2 is expressed in human umbilical vein
      endothelium, but is not involved in the inhibition of adenosine transport induced
      by hyperglycaemia.
AB  - Human equilibrative, Na(+)-independent nucleoside transport is mediated by
      membrane proteins sensitive (system es, hENT1) or insensitive (system ei, hENT2)
      to nitrobenzylthioinosine (NBMPR). Gestational diabetes and elevated
      extracellular concentrations of D-glucose reduce adenosine transport in human
      umbilical vein endothelium (HUVEC). We studied hENT2 and hENT1 expression in
      HUVEC, and the effect of D-glucose on their activity and expression in HUVEC
      preincubated with 25 mM D-glucose (24 h). hENT2 and hENT1 mRNA were quantified by
      real-time reverse transcription polymerase chain reaction, and their proteins
      were detected by Western blotting. hENT2 and hENT1 proteins are co-expressed in
      HUVEC and are located at the plasma membrane, however, hENT2 was mainly
      cytoplasmatic and perinuclear in location. D-Glucose reduced hENT1 and hENT2 mRNA
      expression, but only hENT1 protein abundance at the plasma membrane. Adenosine
      transport was inhibited by D-glucose and NMBPR (1 microM) in intact cells and
      membrane vesicles. Hypoxanthine inhibited adenosine transport in the absence or
      in the presence of 1 microM NBMPR. D-Glucose reduced NBMPR maximal binding in
      intact cells, membrane vesicles, and plasma membrane fractions. In conclusion,
      the present study demonstrates that hENT2 and hENT1 are co-expressed in HUVEC,
      and even when adenosine transport is also mediated by hENT2, the hENT2-mediated
      transport activity is not involved in the d-glucose-induced down-regulation of
      total adenosine transport.

PMID- 16085044
TI  - Glucocorticoids inhibit placental cytokines from cultured normal and preeclamptic
      placental explants.
AB  - Glucocorticoids are used in pregnancy to enhance fetal lung maturity as well as
      to ameliorate antepartum and postpartum HELLP (hemolysis, elevated liver enzymes,
      and low platelet count) syndrome, but it is not clear if glucocorticoids can
      modulate placental cytokine production. The aim of this study is to examine the
      effect of glucocorticoids at equivalent doses used for fetal lung maturity on
      placental tissue production of cytokines (IL-10, IL-6 and TNF-alpha). Placental
      biopsies were taken from the decidual surface of term placentas of normal
      pregnancy (n = 5) and preeclampsia (n = 5). Villous explants were cultured with
      increasing concentrations of glucocorticoids (betamethasone and methyl
      prednisolone, 0.0025 microM, 0.25 microM and 25 microM). The dose effect of
      glucocorticoids on cytokines (TNF-alpha, IL-6 and IL-10) production was examined
      using ELISA. There was a stepwise reduction of TNF-alpha (23.6-97.5% reduction)
      and IL-6 (13.7-71% reduction) with increasing doses of betamethasone and methyl
      prednisolone from placentas of women with preeclampsia and normal pregnancy.
      However, IL-10 was not altered in conditioned medium by increasing doses of
      glucocorticoids. Our data suggest that the ratio of pro-inflammatory to anti
      inflammatory cytokine (Th1/Th2) is potentially altered by exogenous
      glucocorticoids. These changes have a favourable effect on the ratio in
      preeclampsia with a reduction in the potentially vascular active pro-inflammatory
      cytokines but without altering or decreasing the necessary anti-inflammatory
      cytokine IL-10 production in placental tissue.

PMID- 16085045
TI  - Monocyte chemotactic protein-1 expression is increased in human gestational
      tissues during term and preterm labor.
AB  - OBJECTIVE: Microarray analysis was used to characterize the labor-selective
      transcriptome of the human myometrium during labor. One highly up-regulated
      transcript, monocyte chemotactic protein-1 (MCP-1), was further characterized.
      METHODS: Expression of MCP-1 was evaluated in the myometrium, the placenta, the
      gestational membranes (GM) and the amniotic fluid (AF) by real time RT-PCR,
      Northern blot analysis and ELISA. The level of immunoreactive (IR) MCP-1 content
      of primary myometrial cultures treated with inflammatory cytokines was quantified
      by ELISA. RESULTS: Up-regulation of the myometrial MCP-1 transcript in term
      laboring patients was demonstrated by microarray and confirmed by real time (RT)
      PCR and Northern blot analysis. Increased MCP-1 transcripts were demonstrated in
      GM during term labor. The IR content of myometrial MCP-1 was increased during
      term labor and in the AF from patients experiencing preterm delivery. Levels of
      IR MCP-1 increased in myometrial cultures in response to interleukin 1-beta.
      CONCLUSION: The expression of myometrial MCP-1 was significantly increased during
      term labor and was similarly increased in vitro in response to interleukin 1
      beta, a pro-inflammatory substance known to play a role in preterm birth. The
      increased IR content of MCP-1 within the AF preceding preterm delivery may render
      this protein a useful predictor of preterm birth.

PMID- 16085046
TI  - Maternal origin of inflammatory leukocytes in preterm fetal membranes, shown by
      fluorescence in situ hybridisation.
AB  - The aim of this study was to determine the maternal or fetal origin of
      inflammatory leukocytes in fetal membranes from cases of chorioamnionitis. Fetal
      membranes were collected from male preterm infants and chorioamnionitis was
      diagnosed histologically. Fluorescence in situ hybridisation for X and Y
      chromosomes was used to determine the gender of infiltrating leukocytes in the
      chorion and amnion. Leukocytes, trophoblast and mesenchymal cells were identified
      using immunohistochemistry for CD45, cytokeratin-7 and vimentin, respectively.
      Leukocytes present in the chorion and amnion were labelled XX, indicating
      maternal origin, and these cells were immunoreactive for the leukocyte marker
      CD45 but not for vimentin or cytokeratin-7. All other cells in the chorion and
      amnion were labelled XY and of fetal origin. The results indicated that maternal
      leukocytes invade the amnion and chorion in chorioamnionitis and we suggest that
      this is part of the maternal inflammatory response to intrauterine infection.

PMID- 16085047
TI  - Experimental transplantation study for possible transformation of bone marrow
      cells in the mouse placenta.
AB  - The aim of the present study is to establish a mouse model of the transplantation
      of bone marrow cells into the placenta in mid-gestation. The mononuclear fraction
      of bone marrow cells was isolated by Ficoll gradient centrifugation from the
      femur bones of C57BL/6 green fluorescent protein (GFP) gene transgenic (Tg) mice.
      After intraperitoneal injection of pentobarbital sodium, the abdominal cavities
      of pregnant non-Tg (C57BL/6 or ICR) mice were opened at 9.5 days postcoitum
      (dpc). The mononuclear fraction of bone marrow cells from Tg mice (3-5 x
      10(5)cells/3 microl) was directly injected into the placental portion of the
      pregnant uterus, at a depth of approximately 3 mm, using a 31-gauge injector. The
      placenta was sampled at 14.5 dpc. Confocal laser scanning microscopic analysis of
      the serial sections of the sampled placenta (150-250 sections/placenta) was
      carried out to detect GFP-positive cells and to assess immunostaining for
      cytokeratin, CD34, p57(Kip2) and prolactin. Most pregnant mice survived until
      sampling of the placenta at 14.5-18.5 dpc (88.9% for C57BL6 and 100% for ICR).
      The survival rate of fetuses from mice in which the placenta was transplanted
      with GFP-positive bone marrow cells was approximately 50%. A small population
      (0.154%) of injected bone marrow cells was retained in the placental tissue.
      Immunohistochemically, cytokeratin, CD34 and p57(Kip2) were positively stained in
      0.062%, 4.5% and 2.1% of GFP-positive cells, respectively, while prolactin was
      not positive in any of the cells examined. GFP-positive bone marrow cells were
      successfully transplanted to the murine placenta. Future investigations of the
      specific antigens in bone marrow cells retained in the placenta may enable a
      better understanding of the local regulation of placental development.

PMID- 16085048
TI  - Intercellular fusion of BeWo.

PMID- 16085049
TI  - Testosterone increases display behaviors but does not stimulate growth of adult
      plumage in male golden-collared manakins (Manacus vitellinus).
AB  - In order to attract females, male golden-collared manakins gather in leks and
      perform a complex display consisting of acrobatics accompanied by loud
      "wingsnapping". During this display, males show off their yellow beard and
      yellow, black, and green plumage that is striking in comparison to the dull green
      plumage of young males and females. We investigated the role of testosterone (T)
      in activating the display of manakins and in stimulating the growth of the adult
      male plumage. T regulates song, copulation, and territorial aggression in
      temperate species. In tropical species, however, T levels can be relatively low
      year round, which has raised questions about the involvement of T in courtship
      display and male aggression in these species. In neither temperate nor tropical
      species has the role of hormones in the shift from juvenile to adult plumage been
      well studied. Therefore, we implanted green-plumaged birds and adult males with
      either a T pellet or an inert pellet (controls) and observed the display
      behaviors of these birds in the field and in captivity. In captive birds, we also
      plucked feathers from sexually dimorphic regions and observed color and
      regeneration rate of new feathers. We found that birds implanted with T increased
      several display behaviors compared to controls. All plucked feathers grew back
      the same color as prior to treatment; however, we observed some differences in
      feather growth rate between T-treated birds and controls.

PMID- 16085050
TI  - Acid sensing ionic channels: modulation by redox reagents.
AB  - Acid-sensing ion channels (ASICs) are widely expressed in mammalian sensory
      neurons and supposedly play a role in nociception and acid sensing. In the course
      of functioning the redox status of the tissue is subjected to changes. Using
      whole-cell patch-clamp/concentration clamp techniques we have investigated the
      effect of redox reagents on the ASIC-like currents in the sensory ganglia and
      hippocampal neurons of rat. The reducing agent dithiothreitol (DTT), when applied
      in the concentrations 1-2 mM, reversibly potentiates proton-activated currents,
      while the oxidizing reagent 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) causes
      their inhibition. The EC50 and Hill coefficient for the activation of ASIC-like
      currents by protons are not affected by DTT. Redox modulation of proton-activated
      currents is independent on the membrane potential and on the level of pH used for
      the current activation. The endogenous antioxidant tripeptide glutathione (its
      reduced form, g-l-glutamyl-l-cysteinyl-glycine, GSH) also potentiates proton
      activated currents. Our results indicate that ASIC-like currents are susceptible
      to regulation by redox agents.

PMID- 16085051
TI  - Cation-independent mannose 6-phosphate and 78 kDa receptors for lysosomal enzyme
      targeting are located in different cell compartments.
AB  - The distribution of the cation-independent mannose 6-phosphate and 78 kDa
      receptors was studied in postnuclear subcellular fractions from two rat liver
      cell lines. ELISA assays revealed that the mannose 6-phosphate receptor is
      enriched in the light buoyant Percoll fractions that contain Golgi structures and
      early endosomes. Most of the 78 kDa receptor is localized in a heavy fraction at
      the bottom of the Percoll gradient and smaller amounts in the endosomal
      fractions. The high-density compartment is denser than lysosomes, contains LAMP2
      but not LIMPII or acid hydrolases, and is not disrupted with glycyl-l
      phenylalanine 2-naphthylamide, a substrate for cathepsin C that selectively
      disrupts lysosomes. Immunofluorescence microscopy studies indicate no
      colocalization of the 78 kDa receptor with the mannose 6-phosphate receptor or
      LIMPII. Mannose 6-phosphate-independent endocytosed beta-glucuronidase was found
      in the lysosomal, the early and late endosomal fractions. These fractions were
      immunoadsorbed in columns containing antibodies against the 78 kDa receptor. Only
      the endocytosed beta-glucuronidase present in the early and late endosomal
      fractions is associated to immunoadsorbed vesicles. In these vesicles, LAMP2 was
      detected but no LIMPII or the mannose 6-phosphate receptor. Results obtained
      suggest that the 78 kDa receptor is found along the endocytic pathway, but in
      vesicles different from the cation-independent mannose 6-phosphate receptor.

PMID- 16085052
TI  - Effector-induced Syk-mediated phosphorylation in human erythrocytes.
AB  - Band 3 (AE1), the most prominent polypeptide of the human erythrocyte membrane,
      becomes heavily tyrosine phosphorylated following treatment of intact cells with
      protein tyrosine phosphatase inhibitors such as diamide, pervanadate, vanadate,
      or N-ethylmaleimide (NEM). The mechanism underlying this tyrosine phosphorylation
      is thought to involve the sequential action of two protein tyrosine kinases, Syk
      (p72syk) and Lyn (p53/56lyn). While Lyn catalysed phosphorylation appears to be
      strictly dependent on prior phosphorylation of Tyr8 and 21 of band 3 by Syk,
      little is known about the mechanism of induction of Syk phosphorylation. Data
      presented here show that both the fraction of Syk that associates with the
      membrane and the extent of phosphorylation of band 3 differ in response to the
      above inhibitors. While diamide and NEM stimulate syk translocation to the
      membrane during their induction of band 3 tyrosine phosphorylation, pervanadate
      and vanadate induce no change in kinase distribution. Moreover, diamide and NEM
      induced Syk recruitment to the membrane are phosphotyrosine independent and
      involve their preferential association with Triton X-100-insoluble membrane
      skeletons. Together these data reveal a complex process controlling the
      association and catalytic activity of protein tyrosine kinases syk and lyn with
      the human erythrocyte membrane.

PMID- 16085053
TI  - CCAAT/enhancer binding protein alpha maintains the ability of insulin-stimulated
      GLUT4 translocation in 3T3-C2 fibroblastic cells.
AB  - In 3T3-L1 preadipocytes, hormonal induction causes adipose conversion and
      facilitates the expression of insulin-sensitive glucose transporter, GLUT4.
      Evidence has accumulated that, in 3T3-L1 preadipocytes, the formation of GLUT4
      storage vesicle and its translocation to plasma membrane precede both lipid
      accumulation and expression of GLUT4 and C/EBPalpha, a key transcription factor
      for adipose differentiation. On the other hand, 3T3-C2 fibroblastic cells, a
      subline of 3T3-L1, follow adipogenic process till mitotic clonal expansion stage
      (2 days after hormonal induction), but do not proceed to terminal differentiation
      stage (8 days after the induction), resulting in a lack of adipose conversion and
      GLUT4 expression. Here we show that, when myc-tagged GLUT4 was retrovirally
      expressed in 3T3-C2 cells, insulin-stimulated GLUT4 translocation did occur on
      day 2 after the induction. On day 8 after the induction, however, neither GLUT4
      translocation nor the expression of C/EBPalpha was observed. We also created 3T3
      C2 cells stably expressing both myc-tagged GLUT4 and C/EBPalpha, demonstrating
      that co-expressed cells showed insulin-stimulated GLUT4 translocation on day 8
      after the induction, as well as adipose conversion coupling with PPARgamma
      expression. Our results provide evidence that C/EBPalpha has the potential to
      maintain the ability of insulin-stimulated GLUT4 translocation in C/EBPalpha
      deficient 3T3-C2 fibroblastic cells.

PMID- 16085054
TI  - Regulation of Bcl-2 and Bcl-xL anti-apoptotic protein expression by nuclear
      receptor PXR in primary cultures of human and rat hepatocytes.
AB  - The pregnane X receptor (PXR) plays a major role in the protection of the body by
      regulating the genes involved in the metabolism and elimination of potentially
      toxic xeno- and endobiotics. We previously described that PXR activator
      dexamethasone protects hepatocytes from spontaneous apoptosis. We hypothesise a
      PXR-dependent co-regulation process between detoxication and programmed cell
      death. Using primary cultured human and rat hepatocytes, we investigated to
      determine if PXR is implicated in the regulation of Bcl-2 and Bcl-xL, two crucial
      apoptosis inhibitors. In the present study we demonstrated that the treatment of
      primary cultured hepatocytes with PXR agonists increased hepatocyte viability and
      protects them from staurosporine-induced apoptosis. The anti-apoptotic capacity
      of PXR activation was correlated with Bcl-2 and Bcl-xL induction at both the
      transcriptional and protein levels in man and rats, respectively. The inhibition
      of PXR expression by antisense oligonucleotide abolished PXR activators Bcl-xL
      induction. Accordingly, PXR overexpression in HepG2 cells led to bcl-2 induction
      upon clotrimazole treatment and protects cells against Fas-induced apoptosis. Our
      results demonstrate that PXR expression is required for Bcl-2 and Bcl-xL up
      regulation upon PXR activators treatment in human and rat hepatocytes. They also
      suggest that PXR may protect the liver against chemicals by simultaneously
      regulating detoxication and the apoptotic pathway.

PMID- 16085055
TI  - Regulation of the release and function of tumor cell-derived soluble CD44.
AB  - CD44, a major receptor for glycosaminoglycan hyaluronan (HA), is a broadly
      distributed cell surface glycoprotein implicated in multiple functions, including
      tumor growth and dissemination. The affinity of surface CD44 for HA is subject to
      regulation at several levels. CD44 is found in multiple phases, including as an
      integral transmembrane protein and as soluble fragment of the extracellular
      domain found in the circulation and other body fluids. Transmembrane CD44 and its
      ability to interact with HA have been a focus of numerous studies in the past,
      but the function of soluble CD44 remains obscure. Interestingly, malignant
      diseases are often associated with an increase in the plasma level of CD44. The
      delineation of the HA binding capacity of tumor-derived soluble CD44 is an
      important step toward understanding the biological function of this molecule. In
      this study, we demonstrate that tumor cells activated to bind HA by cytokines
      rapidly release CD44 upon treatment with phorbol ester (PMA). The affinity for HA
      of the soluble CD44 released in response to PMA varied depending on the cytokine
      pretreatment. These results suggest that the function of tumor-derived soluble
      CD44, like the transmembrane form of the receptor, can be regulated.

PMID- 16085056
TI  - Y+ and y+ L arginine transporters in neuronal cells expressing tyrosine
      hydroxylase.
AB  - Arginine is a semi-essential amino acid that serves as sole substrate for enzymes
      involved in diverse cell processes including redox balance via nitric oxide
      synthase (NOS) and cell proliferation via arginase. Neurons that express nNOS
      require intracellular arginine to generate nitric oxide (NO). Using a TH+
      neuronal cell line (CAD cells), we show that neuronal NO production is largely
      dependent on extracellular arginine. Although a small intracellular pool exists
      in CAD cells, the lack of mRNA for argininosuccinate synthase (AS), a rate
      limiting enzyme for arginine recycling, suggests that intracellular pools are not
      re-supplied by this mechanism in this sub-class of neurons. Rather, arginine is
      taken up from the extracellular media by two primary transport systems, the y+
      and the y+ L systems. The expression of CAT1, CAT3, y+ LAT1 and y+ LAT2 mRNAs
      supports the presence of each system. CAD cell arginine transport is depressed by
      increased extracellular K+ levels and demonstrates that variations in membrane
      potential control neuronal arginine uptake. Short term exposure to the oxidizing
      agents, rotenone and Angeli's salt, but not FeSO4, increases arginine transport.
      The regulation of arginine uptake by physiological factors suggests that arginine
      supply adapts in a moment-to-moment fashion to the changing needs of the neuron.

PMID- 16085057
TI  - Alsin is partially associated with centrosome in human cells.
AB  - Mutations in the ALS2 gene has recently been linked to cases of juvenile
      amyotrophic lateral sclerosis, juvenile primary lateral sclerosis and ascending
      hereditary spastic paralysis. All reported mutations predict the production of
      truncated forms of Alsin suggesting a loss of function mechanism for these motor
      neuron disorders. Here we used the tetracycline-regulated expression system to
      overexpress the full-length and truncated forms of Alsin in different cell lines.
      Alsin overexpression caused severe phenotypic changes in monkey COS-7 cells
      including the enlargement and accumulation of early endosomes, impairment of
      mitochondria trafficking and fragmentation of the Golgi apparatus. Our results
      further demonstrate the requirement of the Alsin VPS9 domain for occurrence of
      the vacuolation process and the role of Alsin as a guanine nucleotide exchange
      factor for Rab5. Transfected human SW13 cells exhibited an unexpected centrosomal
      localization for Alsin that was linked to the presence of the c-terminal part of
      the protein. Immunofluorescence staining revealed a colocalization of Alsin with
      the centrosomal markers gamma-tubulin and A kinase anchoring protein (AKAP-450).
      Similar results were obtained with human LA-N-2 and SK-N-SH neuronal cells.
      Moreover endogenous Alsin was detected in a centrosome preparation purified from
      human cortical brain. Considering the crucial role of centrosome in the
      production of microtubules required for intracellular transport, these findings
      are of potential relevance for unravelling the disease mechanisms linked to Alsin
      mutations.

PMID- 16085058
TI  - Bcl-xL/Bax ratio is altered by IFNgamma in TNFalpha- but not in TRAIL-induced
      apoptosis in colon cancer cell line.
AB  - Apoptosis is a crucial mechanism to eliminate harmful cells in which growth
      factors and cytokines are key regulators. In HT29-D4 cells, a model of human
      colon carcinoma, IFNgamma presensitization is essential to induce an apoptotic
      response to TNFalpha whereas it only slightly enhances TRAIL-induced apoptosis.
      To compare the transcriptional profiles induced by TNFalpha and TRAIL and their
      regulation by IFNgamma, we optimized a cDNA array analysis on targeted signaling
      pathways and confirmed the gene expression modulations by comparative RT-PCR.
      Although the two TNFSF ligands induced a same strong up-expression of pro
      apoptotic Bax gene, the expression of anti-apoptotic Bcl-xL gene was more
      strongly up-regulated in TNFalpha- than in TRAIL-stimulated cells. Thus, TRAIL
      but not TNFalpha induced apoptotic mitochondrial cascade as highlighted by
      cytochrome c release into cytosol. IFNgamma presensitization of TRAIL-stimulated
      cells did not induce any change in cytochrome c release, suggesting that the
      increase of IFNgamma/TRAIL-induced apoptosis is independent of this pathway. In
      contrast, IFNgamma pretreatment prevented Bcl-xL gene up-expression in TNFalpha
      stimulated cells and allowed cytochrome c release. Thus, we hypothesize that the
      Bcl-xL/Bax ratio can block the apoptotic response in TNFalpha-stimulated cells
      but allows cell death initiation when it is altered by a crosstalk between
      IFNgamma presensitization and TNFalpha induced signalings.

PMID- 16085059
TI  - Effects of agmatine accumulation in human colon carcinoma cells on polyamine
      metabolism, DNA synthesis and the cell cycle.
AB  - Putrescine, spermidine and spermine are low molecular polycations that play
      important roles in cell growth and cell cycle progression of normal and malignant
      cells. Agmatine (1-amino-4-guanidobutane), another polyamine formed through
      arginine decarboxylation, has been reported to act as an antiproliferative agent
      in several non-intestinal mammalian cell models. Using the human colon
      adenocarcinoma HT-29 Glc(-/+) cell line, we demonstrate that agmatine, which
      markedly accumulated inside the cells without being metabolised, exerted a strong
      cytostatic effect with an IC50 close to 2 mM. Agmatine decreased the rate of L
      ornithine decarboxylation and induced a 70% down-regulation of ornithine
      decarboxylase (ODC) expression. Agmatine caused a marked decrease in putrescine
      and spermidine cell contents, an increase in the N1-acetylspermidine level
      without altering the spermine pool. We show that agmatine induced the
      accumulation of cells in the S and G2/M phases, reduced the rate of DNA synthesis
      and decreased cyclin A and B1 expression. We conclude that the anti-metabolic
      action of agmatine on HT-29 cells is mediated by a reduction in polyamine
      biosynthesis and induction in polyamine degradation. The decrease in
      intracellular polyamine contents, the reduced rate of DNA synthesis and the cell
      accumulation in the S phase are discussed from a causal perspective.

PMID- 16085060
TI  - Aluminum exposure affects transferrin-dependent and -independent iron uptake by
      K562 cells.
AB  - Aluminum (Al) and iron (Fe) share several physicochemical characteristics and
      they both bind to transferrin (Tf), entering the cell via Tf receptors (TfR).
      Previously, we found similar values of affinity constant for the binding of TfR
      to Tf carrying either Al or Fe. The competitive interaction between both metals
      prevented normal Fe incorporation into K562 cells and triggered the upregulation
      of Fe transport. In the present work we demonstrated that Al modified Fe uptake
      without affecting the expression of Tf receptors. Both TfR and TfR2 mRNA levels,
      evaluated by RT-PCR, and TfR antigenic sites, analyzed by flow cytometry, were
      found unchanged after Al exposure. In turn, Al did induce upregulation of non-Tf
      bound Fe (NTBI) uptake. This modulation was not due to intracellular Fe decrease
      since NTBI transport proved not to be regulated by Fe depletion. Unlike its
      behavior in the presence of Tf, Al was unable to compete with NTBI uptake,
      suggesting that both metals do not share the same alternative transport pathway.
      We propose that Al interference with TfR-mediated Fe incorporation might trigger
      the upregulation of NTBI uptake, an adaptation aimed at incorporating the
      essential metal required for cellular metabolism without allowing the
      simultaneous access of a potentially toxic metal.

PMID- 16085061
TI  - Thyroid cancer in pregnancy.
AB  - OBJECTIVE: To compare stage at diagnosis, treatment and survival among pregnant
      women with thyroid cancer to non-pregnant women with thyroid cancer, and to
      assess the impact of treatment on maternal and perinatal outcomes. METHODS: A
      database containing maternal and newborn discharge records linked to the
      California Cancer Registry was queried to obtain information on all thyroid
      cancers from 1991-1999. Women with thyroid cancer occurring during pregnancy were
      compared to age-matched non-pregnant women with thyroid cancer. RESULTS: 595
      cases of thyroid cancers were identified (129 antepartum and 466 postpartum).
      About 64% of thyroid cancers were diagnosed at stage 2 among pregnant women
      versus 58% among non-pregnant controls. The odds of thyroid cancer were 1.5 times
      higher among Asian/Pacific Islanders than among Non-Hispanic White women.
      Pregnancy had no significant effect on mortality after diagnosis of thyroid
      cancer. Thyroidectomy during pregnancy was not associated with adverse maternal
      or neonatal outcomes. CONCLUSIONS: Thyroid cancer discovered during or after
      pregnancy does not appear to have a significant impact on the prognosis of the
      disease.

PMID- 16085062
TI  - The relationship between age and carotid artery intima-media thickness,
      hemoglobin A1c in nondiabetic, healthy geriatric population.
AB  - The aim of the study was to investigate a casual relationship between age and
      carotid artery intima-media thickness (IMT) and hemoglobin A1c (HbA1c) levels and
      to assess the effects of possible risk factors in healthy nondiabetic elderly.
      Seventy-two healthy, well-educated, nondiabetic, healthy elderlies (mean age:
      71.5+/-5.01 years; 43 male, 29 female) were enrolled in the study. Comprehensive
      assessments including a battery of psychosocial and functional performance tests
      were performed to all subjects. All of them were also asked about health
      prevention topics including exercise, dietary habits, smoking, vaccination,
      cholesterol screening, etc. Carotid artery IMT was measured by ultrasound. Blood
      samples were obtained for fasting glucose, HbA1c, cholesterol, triglyceride and
      fibrinogen. The mean carotid artery IMT was 0.94+/-0.13 mm and the mean HbA1c
      level was 5.29+/-0.65 mg/dl. There was no significant correlation between age and
      carotid artery IMT (r(s)=0.15), HbA1c levels (r(s)=-0.08) and other possible
      atherosclerosis risk factors. Also there was no correlation between carotid
      artery IMT and HbA1c levels (r(s)=0.14). Our data indicated that the carotid
      artery IMT, HbA1c and age are not associated in a geriatric healthy, well
      educated population. Comparative studies done on the elderly who do not benefit
      from preventive health care programs are needed to establish if preventive health
      care measures and risk factor modification are important in the elderly age
      group.

PMID- 16085063
TI  - Lack of association of cathepsin D genetic polymorphism with Alzheimer's disease
      in Koreans.
AB  - Cathepsin D (CatD) is a good candidate susceptibility marker for Alzheimer's
      disease (AD), since it was found to be involved in the processing of the amyloid
      precursor protein and the formation of the hyperphosphorylated tau. And recently,
      a CatD genetic polymorphism was found to be associated with the risk of
      Alzheimer's disease (AD) in a German population. However, the CatD T-AD
      association has not been replicated in a series of the successive independent
      studies in other races. Therefore, we determined CatD genotypes to examine the
      possible association of the CatD polymorphism with AD in Koreans. We failed to
      find significant association between the CatD T allele and AD. In addition, the
      CatD T--AD association was not significant regardless of the age at onset or the
      occurrence of the apolipoprotein epsilon4 allele. However, we cannot exclude the
      possible contribution of the CatD in the development of AD, since the power of
      the present study was not high enough because of low allelic frequency of the
      CatD T in Koreans and small sample size. In conclusion, the association between
      the CatD genetic polymorphism and AD was not found in Koreans, although it waits
      for further replication in an extended sample.

PMID- 16085064
TI  - Caregivers' expectations and care receivers' competence Lawton's ecological model
      of adaptation and aging revisited.
AB  - Drawing upon Lawton's ecological model of adaptation and old age, this study
      analyses the implications of the degree of adjustment (congruence) between the
      self-assessed functional capacity of 33 community-dwelling elderly care receivers
      and their functional capacity as assessed by their respective family caregivers
      (N=33), for the adaptation of the elderly and for their caregivers' feelings of
      burden, defined as their perception of how the caregiving activity is affecting
      their physical, psychological and social well-being. Three groups were set up on
      the basis of the level of congruence between caregivers' and care receivers'
      reports: high capacity attribution, coincidental capacity attribution, and low
      capacity attribution groups. No group differences were found in the care
      receivers' level of functional independence as perceived by their caregivers and
      as assessed by the Katz Index and the Instrumental Activities of Daily Living
      scale. However, the results showed differences between the three groups in
      relation to both the care receivers' adaptation when viewed in terms of their
      psychological well-being and self-efficacy. Differences between the caregivers'
      perceived sense of burden and their perception of their relatives' independence
      were also found. As proposed by the Lawton model, the results support the
      psychological benefits, both for the caregiver and the care receiver, of an
      appropriate balance between the socio-environmental demands (caregivers'
      expectations regarding care receivers' competence) and the capacity of the
      individual.

PMID- 16085065
TI  - Frailty, morbidity and survival.
AB  - Frailty, as a reflection of decreased physical reserve rather than disability, is
      assessed by various functional tests rather than by specific disease burden. We
      investigated association of measures of frailty to disease outcomes and survival
      in a population-based study of Midwestern adults. The markers of frailty we
      evaluated were: time to walk a measured course (gait-time), handgrip strength,
      peak respiratory flow rate, ability to stand from a sitting position without
      using arms, and best corrected visual acuity. A history of cardiovascular
      disease, cancer, and hypertension were obtained. Data were collected at the third
      examination (1998--2000) of the Beaver Dam Eye Study cohort (n=2962). Follow-up
      for mortality occurred up to 412 years after the 1998--2000 examinations. Markers
      of frailty were significantly associated with age. Values in the highest quartile
      (slowest) of gait-time, lowest quartile of peak expiratory flow rate, lowest
      quartile of handgrip strength, inability to stand from sitting in one try (those
      not in a wheelchair), and visual impairment were combined in an index to denote a
      general description of frailty. The range of the index was 0 (no frailty) to 5
      (maximum frailty). Greater frailty was significantly associated with
      cardiovascular disease and hypertension. Frailty was associated with poorer
      survival over an interval of 412 years after adjusting for age, sex,
      hypertension, diabetes, and cardiovascular disease. Greater frailty was
      associated with greater likelihood of concurrent medical conditions and with
      decreased survival.

PMID- 16085066
TI  - Effect of diet and red wine consumption on serum total antioxidant capacity
      (TAC), dehydroepiandrosterone-sulphate (DHEAS) and insulin-like growth factor-1
      (IGF-1) in Italian centenarians.
AB  - The traditional mediterranean diet is associated with a hope for longer survival.
      It has also been shown that the red wine possesses a protective effect against
      the oxidative stress. We studied TAC, the DHEAS and the IGF-1 in a group of 26
      healthy centenarians, 17 women and 9 men, of the age range of 100--105 years.
      Furthermore, we analyzed also serum urate and bilirubin levels between drinkers
      and abstainers. Most of centenarian subjects have been moderate wine consumers
      (<500 ml/day of red wine). These subjects were subdivided as follows: (i) Group
      A: those who had maintained the style of their dietary habits as compared to the
      previous years (n=3 males, 10 females); (ii) Group B: those who actually consumed
      a diet being deficient compared to that of the previous years, but remained
      moderate drinkers of red wine (n=3 males, 4 females); and (iii) Group C: those
      who actually consumed a diet being deficient compared to that of the previous
      years, and at the same time, were abstainers in wine consumption (n=3 males, 3
      females). The results show that in men three of the studied parameters decreased
      from Group A to C to considerable extents, as follows (mean+/-S.D.). TAC: 302.4+/
      32.3; 142.0+/-24.1 and 96.4+/-20.1 micromol/l; DHEAS: 3.35+/-0.81; 2.52+/-0.18
      and 1.34+/-0.14 micromol/l; IGF-1: 85.7+/-6.7; 76.6+/-6.7 and 65.6+/-2.6 ng/ml,
      respectively. For the same parameters, the results in the women were: TAC:
      258.4+/-12.2; 182.1+/-14.0 and 107.6+/-10.0 micromol/l; DHEAS: 3.85+/-0.16;
      2.34+/-0.19 and 2.05+/-0.04 micromol/l; IGF-1: 89.7+/-6.7; 76.6+/-4.7 and 64.2+/
      2.7 ng/ml, respectively. We did not find any significant difference in the other
      serum parameters between drinkers (n=14) and abstainers (n=3) (urate: 267.6+/
      52.9, and 289.5+/-80.1; bilirubin: 9.81+/-4.29 and 7.18+/-2.89 micromol/l,
      respectively). Our data suggest that the deteriorated diet caused a reduction of
      TAC, DHEAS and IGF-1 in the centenarians. However, red vine consumption exerted a
      protective effect against this trend, even if this protection is not reaching
      statistical significance in some cases (in men), which is due most probably to
      the lower number of male subjects in the study.

PMID- 16085067
TI  - Influence of behavioral and psychological symptoms of dementia (BPSD) and
      environment of care on caregivers' burden.
AB  - With increasing population of older adults in need of care, caregiver's burden is
      becoming a major concern. We investigated the relative contributions of BPSD of
      care recipients, caregiver's background and the care environment to caregiver's
      burden assessed by using Zarit burden interview (ZBI). Among BPSD, inability of
      finding the way home, inability of managing money and fecal incontinence were the
      most difficult symptoms to cope with. A path analysis, by which we constructed a
      network model to clarify the contributions of the factors examined to the
      caregiver's burden, indicated that the severity of dementia, the feeling of
      "would rather die than be in the same condition" and the physical pain of the
      caregivers showed great direct influences on the score of the ZBI. In conclusion,
      we clarified kinetic and dynamic interactions of factors affecting caregiver's
      burden by using a path analysis. The model indicates that the caregiver's burden
      can be affected not merely by the illness of the care recipients but by the
      caregiver's background and the care environment.

PMID- 16085068
TI  - Determinants of the subjective functional outcome of total joint arthroplasty.
AB  - The aim of the study is three-fold: (i) to analyze association between early
      subjective functional outcome of total joint arthroplasty (TJA) and patient
      related risk factors; (ii) to evaluate the six-month subjective functional
      outcome of TJA as compared with subjective functional status of non-operated
      outpatients; (iii) to evaluate TJA self-perceived amelioration rates compared to
      the status of an age-matched sample from a general medical practice. A
      prospective consecutive study was performed upon 100 elderly inpatients with
      recent primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) for
      osteoarthritis. Interviews on preoperative status and short-term outcome were
      performed at admission and six months after surgical intervention with Western
      Ontario and MacMasters Universities Osteoarthritis Index (WOMAC). One hundred
      aged-matched consecutive outpatients were screened for osteoarthritis and
      interviewed with the same questionnaire in a single session. Differences between
      baseline and follow-up scores were evident and statistically significant for both
      TJA groups, although THA patients showed more improvement. The comparison between
      TJA patients at baseline and age-matched osteoarthritis outpatients highlighted
      less impairment among outpatients. The situation reversed six months after the
      intervention. Objective functional outcome of post-operative rehabilitation has
      not revealed predictive value for the six-month outcome of TJA in terms of self
      perceived functional status. Logistic regression analysis indicated that
      preoperative status was the only significant predictor of higher WOMAC scores six
      months after TJA. The survey confirms the early benefit of THA or TKA for
      osteoarthritis, but a less favorable subjective functional outcome is expected at
      six months when preoperative subjective functional status is severely
      compromised.

PMID- 16085069
TI  - Self-perceived distress and self-perceived functional recovery after recent total
      hip and knee arthroplasty.
AB  - The research was aimed at verifying whether psychological distress and depression
      are associated to reduced functional improvement following arthroplasty. Thirty
      six patients with total knee arthroplasty (TKA) and 36 patients total hip
      arthroplasty (THA) were enrolled at the beginning of their rehabilitation. The
      mean age in TKA patients was 71.3+/-7.8 years (S.D.). The mean age in THA
      patients was 67.9+/-8.4 years. The Western Ontario and MacMasters Universities
      Osteoarthritis Index (WOMAC) and the Hospital Anxiety and Depression (HAD) were
      applied. Forty-four percent of THA and 58% of TKA showed over-threshold HAD
      scores at admission. The proportion was even higher considering HAD-Depression
      sub-scale, where 55% of THA and 61% of TKA patients had over-threshold scores.
      Lack of depression prompted better functional outcome in TKA. The effect of
      depression on TKA functional improvement was still significant after adjusting
      for age and sex. No association was found for THA patients. In order to maximize
      rehabilitation benefit it is then suggested that patients with recent TKA
      intervention are screened for distress and depression at admission and that
      psychological symptoms are treated if over-threshold.

PMID- 16085070
TI  - Colon resection in elderly patients: comparison of data of a single surgical
      department with collective data from the Czech Republic.
AB  - Colorectal cancer is predominantly a disease of elderly people, since over 70% of
      cases occur in those aged 65 years or older. Clinicians have to frequently decide
      whether major surgery is justified in elderly patients with a limited life
      expectancy. Our retrospective study was aimed to compare outcomes of primary
      surgery for colorectal cancer in the elderly patient population. The evaluated
      data were collected from the 1st Department of Surgery, Charles University, and
      from all over the Czech Republic. Patients were divided into three groups: the
      young-old (21-59 years), the older-old (60-69 years), and the oldest-old (>69
      years) patients. In the collective data the youngest and the oldest groups differ
      significantly in the rate of early postoperative complications (12.3% versus
      17.6%, p<0.001). The number of complications associated with the emergency
      procedures was twice as high compared to elective surgery in all groups
      (p<0.001). There was no correlation between age and length of hospital stay in
      the single surgery department. These data suggest that major oncology procedures
      may be undertaken in older patients in whom operative risk is reasonable, with
      acceptable rates of complications.

PMID- 16085071
TI  - Alcohol abuse and dependence in elderly emergency department patients.
AB  - Although elderly people are particularly vulnerable to the adverse effects of
      alcohol, alcohol use disorders in late life have received relatively little
      attention in the literature. Our objectives were to assess the prevalence of
      alcohol use disorders (abuse and dependence), the medical profile and
      psychosocial characteristics in elderly people visiting emergency department
      (ED). A cohort of 2405 patients aged over 60 who came to the ED of a university
      hospital during a 3-month period was studied. Alcohol use disorder diagnosis (DSM
      IV), medical profile and social characteristics were collected from retrospective
      review of patient files. The data derived from 128 patients (mean age, 69.8+/-6.8
      years; 87% males) with alcohol use disorders and 128 non-alcoholic controls. The
      prevalence of current alcohol use disorder was 5.3%. The most common current
      alcohol-induced disorders were alcohol intoxication and alcohol-induced mood
      disorder. Social factors associated with alcohol use disorders were being
      homeless, living alone, being divorced and never married. Falls and delirium were
      frequent ED admission circumstances in elderly drinkers. Drinkers more commonly
      presented with gastrointestinal disorders. In conclusion, alcohol use disorders
      among older patients admitted in ED are common and occur more frequently among
      men. Falls and delirium are the main ED admission circumstances in elderly
      drinkers. Alcohol use disorders are also associated with gastrointestinal
      problems.

PMID- 16085072
TI  - Gender differences in platform measures of balance in rural community-dwelling
      elders.
AB  - The purpose of this study was to establish the age-related reference values of
      the platform measures of balance, which would serve as a baseline for comparing
      the postural insecurity of patients, and to clarify the characteristics of
      balance in community-dwelling elders. A total of 343 participants consisting of
      107 males and 236 females, aged 55--83 years, were investigated in this study.
      The movement of the center of pressure (COP) was measured using a stable force
      platform to quantify postural stability. The examination was performed twice,
      each lasting for 30s, under open-eyes and closed-eyes conditions. In both
      genders, the movement of the COP showed a significant increase with age. Males
      showed a stronger positive correlation between age and platform measures and
      significantly higher levels of amplitude when compared with females. The movement
      of the COP increased under closed-eyes condition, particularly in males. The
      characteristics of balance differed between the genders. That is, males swayed
      more under both open-eyes and closed-eyes conditions, and were more influenced by
      visual deprivation than females.

PMID- 16085073
TI  - Bubble-test method for synthetic and bovine vascular material.
AB  - A measurement system has been designed and constructed at NIST for the study of
      the mechanical properties of synthetic and bovine vascular materials. The
      measurement technique was validated on latex, where good agreement was found with
      the Neo-Hookean model. Measurements were also made on expanded
      polytetrafluoroethylene, which is commonly used for vascular grafts. The
      measurements of this material were carried out over a pressure range greater than
      would be seen in vivo. However, the strains were still small enough to
      effectively apply the Neo-Hookean model to these data.

PMID- 16085074
TI  - Should tendon and aponeurosis be considered in series?
AB  - Fibres, aponeuroses, and tendons are often considered mechanically "in series" in
      skeletal muscles. This notion has led to oversimplified calculations of fibre
      forces from tendon forces, to incorrect derivations of constitutive laws for
      aponeuroses, and to misinterpretations of the recovery of elastic energy in
      stretch-shortening cycles of muscles. Here, we demonstrate theoretically, using
      examples of increasing complexity, that tendon and aponeurosis are not in series
      in a muscle fibre-aponeurosis-tendon complex. We then demonstrate that assuming
      the tendon and aponeurosis to be in series can lead to the appearance of
      mechanical work creation in these passive viscoelastic structures, a result that
      is mechanically impossible. Finally, we explain the mechanical role of the
      incompressible muscle matrix in force transmission from fibres to aponeuroses and
      tendon, and emphasize that incompressibility necessitates the introduction of
      extra forces necessary to maintain this constraint. Unfortunately, this
      requirement eliminates, for all but the simplest cases, a theoretical approach of
      muscle modeling based on intuitive free-body diagrams.

PMID- 16085075
TI  - Bone-implant interface shear modulus and ultimate stress in a transcortical
      rabbit model of open-pore Ti6Al4V implants.
AB  - This experimental study on laser-textured implants aimed to evaluate periimplant
      bone elasticity and ultimate stress of the bone-implant interface in a rabbit
      femur model. After randomization, two cylindrical Ti6Al4V samples (3.5 mm wide,
      5.5 mm long) were transcortically implanted in each femur of 15 female New
      Zealand White Rabbits. Polished implants had been laser-textured with 100, 200,
      and 300 microm diameter pores, and another corundum blasted implant was
      additionally textured with 200 microm pores. Twelve weeks into the experiment, a
      modified push-out test was performed. The median shear modulus indicating the
      elasticity of the periimplant bone was 41.12 MPa for the proximal implant
      location and 25.38 MPa for the distal, without evidence for significant
      differences between implant types. Taking into account the median ultimate shear
      stress for 200 microm implants with and without corundum blasting, no significant
      difference could be demonstrated. However, for blasted 200 microm implants a
      statistically significant (p<0.025) relative gain in ultimate shear stress of 41%
      and 17% was proven in comparison with 100 and 300 microm implants, respectively.
      Non-blasted 200 microm implants reached 48% relative gain in respect of 100
      microm samples.

PMID- 16085076
TI  - Double-step registration of in vivo stereophotogrammetry with both in vitro 6
      DOFs electrogoniometry and CT medical imaging.
AB  - Standard registration techniques of bone morphology to motion analysis data often
      lead to unsatisfactory motion simulation because of discrepancies during the
      location of anatomical landmarks in the datasets. This paper describes an
      iterative registration method of a three-dimensional (3D) skeletal model with
      both 6 degrees-of-freedom joint kinematics and standard motion analysis data. The
      method is demonstrated in this paper on the lower limb. The method includes two
      steps. A primary registration allowed synchronization of in vitro kinematics of
      the knee and ankle joints using flexion/extension angles from in vivo gait
      analysis. Results from primary registration were then improved by a so-called
      advanced registration, which integrated external constraints obtained from
      experimental gait pre-knowledge. One cadaver specimen was analyzed to obtain both
      joint kinematics of knee and ankle joints using 3D electrogoniometry, and 3D bone
      morphology from medical imaging data. These data were registered with motion
      analysis data from a volunteer during the execution of locomotor tasks. Computer
      graphics output was implemented to visualize the results for a motion of sitting
      on a chair. Final registration results allowed the observation of both in vivo
      motion data and joint kinematics from the synchronized specimen data. The method
      improved interpretation of gait analysis data, thanks to the combination of
      realistic 3D bone models and joint mechanism. This method should be of interest
      both for research in gait analysis and medical education. Validation of the
      overall method was performed using RMS of the differences between bone poses
      estimated after registration and original data from motion analysis.

PMID- 16085078
TI  - Packed uniform sphere model for solids: interstitial access opening sizes and
      pressure deficiencies for wetting liquids with comparison to reported
      experimental results.
AB  - Mathematical relationships have been developed to describe the pressure
      deficiencies required for drainage and removal of wetting liquids through the
      access openings to the interstitial void space for a model comprised of uniform
      packed solid spheres. Access openings and associated pressure deficiencies are
      defined in terms of the packing and radius of the spheres, using a circular arc
      approximation for the liquid-vapor portion of the perimeter of the opening. This
      allows determination of equivalent particle radius rather than equivalent
      cylindrical pore radius within a porous solid sample by use of standard pressure,
      porosity and desorption data. For a known particle size and porosity, it allows
      comparison and prediction of drainage of wetting liquids and pressures required
      for removal of the liquid from compacted materials and collections of random
      packed spherical particles. Comparisons are made to experimental packing of
      spheres. Sorption isotherms for a volatile wetting liquid are presented, covering
      the access to the interstitial void space, the pendular liquid ring between
      adjacent touching spheres and the monolayer surface area. The larger size of the
      interstitial void space compared to the size of the access opening leads to lower
      imbibition pressures and hysteresis for both volatile and nonvolatile wetting
      liquids. The relationship to mercury porosimetry and the adjustment for contact
      angles other than 0 degrees and 180 degrees are discussed.

PMID- 16085079
TI  - Designing of the centers for adsorption of bile acids on a silica surface.
AB  - Silicas chemically modified with attached aminopropyl, imidazolyl, and
      trimethylsilyl groups, with adsorptive and coordinative grafted hemin were
      synthesized. Adsorption of some bile acids on the surface of hydroxylated silica,
      synthesized siliceous adsorbents and cholestyramine has been studied. It was
      found that the main contribution to the total adsorption is caused by
      electrostatic attraction between anions of bile acids and positively charged
      sites of the surface of modified silica and also by dispersion interactions
      between steroid skeleton of bile acids and functional groups of modified silicon
      dioxides. It was established that the kinetic parameters of adsorption and
      adsorptive capacity for all investigated siliceous adsorbents exceed similar
      characteristics for cholestyramine. The best of synthesized adsorbents is hemin
      containing adsorbent IX, and the sequence of increase in its adsorptive capacity
      in relation to bile acids corresponds to the following series: I < III < II, IV <
      VI < V < VIII < VII < IX.

PMID- 16085080
TI  - An approach to fouling characterization of an ion-exchange membrane using current
      voltage relation and electrical impedance spectroscopy.
AB  - Fouling phenomena of an anion-exchange membrane by bovine serum albumin (BSA)
      were investigated using current-voltage relation and electrical impedance
      spectroscopy (EIS) in this study. Electrochemical parameters of the Neosepta CMX
      cation- and AMX anion-exchange membrane (Tokuyama Corp., Japan) such as limiting
      current density (LCD), transport number, plateau length, and fraction of the
      conducting phase were measured. Fraction of the conducting phase of the ion
      exchange membranes, calculated from the modified Sand equation, played an
      important role in determining the electrochemical parameters in the presence of
      foulants such as BSA. Fraction of the conducting phase of the AMX membrane
      significantly decreased in the presence of BSA. Two distinguishable slopes were
      observed in the over-LCD region of the current-voltage (I-V) curve, indicating
      the change of resistance. To further elucidate the phenomena, the electrical
      impedance spectroscopic study was carried out using the offset alternating
      current. It was found that the negatively charged loose fouling layer changed to
      the dense deposited BSA on the surface of the AMX membrane occurring along with
      enhanced water dissociation phenomena at the surface of the fouled AMX membrane
      at a higher current density. This result was confirmed by water dissociation
      experiments in a six-compartment electrodialysis cell.

PMID- 16085081
TI  - Adsorption of Basic Yellow 28 from aqueous solutions with clinoptilolite and
      amberlite.
AB  - The objective of this study was to investigate the adsorption of Basic Yellow 28
      that is a cationic dye on clinoptilolite and amberlite XAD-4. Both equilibrium
      and batch rate adsorption in aqueous solutions of the dyestuff were investigated.
      Adsorption rate data were analysed using the pseudo-first order kinetic model of
      Lagergren and the pseudo-second order model to determine adsorption rate
      constants at 20, 30 and 40 degrees C. The adsorption equilibrium data were
      analysed using various adsorption isotherm models and the results have shown that
      adsorption behaviour of Basic Yellow 28 by clinoptilolite and amberlite could be
      described by either Langmuir or Freundlich models. Langmuir adsorption isotherm
      constants corresponding to adsorption capacity, Q(0), were found to be 59.6, 52.9
      and 56.7 mg/g for clinoptilolite at 20, 30 and 40 degrees C, respectively. Lower
      adsorption capacities for Basic Yellow 28 on amberlite were obtained. The
      increase of adsorption rate constants with an increase in temperature for BY 28
      adsorption on amberlite indicated chemisorption with dissociation and increased
      availability of sites due to higher penetration of adsorbing molecules into the
      pores.

PMID- 16085082
TI  - Coating of silica sand with aluminosilicate clay.
AB  - The objective of this work was to coat aluminosilicate clays on an inert silica
      support, and to characterize the properties and stability of the clay-silica
      coating. Two polymers, polyacrylamide (PAM) and polyvinyl alcohol (PVA), were
      used to bind kaolinite, illite, and smectite onto silica grains. The clay-polymer
      composites were studied by X-ray diffraction, FTIR, and electrophoretic mobility.
      Clay coatings on silica grains were characterized by mass coverage, scanning
      electron microscopy, specific surface area, and pH stability. Silica sand was
      successfully coated with clays by using the two polymers, but with PVA, the clay
      coating had a greater mass coverage and was more stable against pH variations.
      Less polymer was needed for the clay coating using PVA as compared to using PAM.
      Clay-polymer complexes and pure clay minerals had similar cation exchange
      capacities and electrophoretic mobilities, indicating that overall surface charge
      of the clays was little affected by the polymers. Some decrease in hydrophilicity
      was observed for illite and smectite when clays where coated with the polymers.
      The methodology reported here allows the generation of a clay-based porous
      matrix, with hydraulic properties that can be varied by adjusting the grain size
      of the inert silica support.

PMID- 16085083
TI  - Electrostatic potential and electroosmotic flow in a cylindrical capillary filled
      with symmetric electrolyte: analytic solutions in thin double layer
      approximation.
AB  - The electrostatic potential in a capillary filled with electrolyte is derived by
      solving the nonlinear Poisson-Boltzmann equation using the method of matched
      asymptotic expansions. This approach allows obtaining an analytical result for
      arbitrary high wall potential if the double layer thickness is smaller than the
      capillary radius. The derived expression for the electrostatic potential is
      compared to numerical solutions of the Poisson-Boltzmann equation and it is shown
      that the agreement is excellent for capillaries with radii greater or equal to
      four times the electrical double layer thickness. The knowledge of the
      electrostatic potential distribution inside the capillary enables the derivation
      of the electroosmotic velocity flow profile in an analytical form. The obtained
      results are applicable to capillaries with radii ranging from nanometers to
      micrometers depending on the ionic strength of the solution.

PMID- 16085084
TI  - A new surface structural approach to ion adsorption: tracing the location of
      electrolyte ions.
AB  - Electrolyte ions differ in size leading to the possibility that the distance of
      closest approach to a charged surface differs for different ions. So far, ions
      bound as outersphere complexes have been treated as point charges present at one
      or two electrostatic plane(s). However, in a multicomponent system, each
      electrolyte ion may have its own distance of approach and corresponding
      electrostatic plane with an ion-specific capacitance. It is preferable to make
      the capacitance of the compact part of the double layer a general characteristic
      of the solid-solution interface. A new surface structural approach is presented
      that may account for variation in size of electrolyte ions. In this approach, the
      location of the charge of the outersphere surface complexes is described using
      the concept of charge distribution in which the ion charge is allowed to be
      distributed over two electrostatic planes. It was shown that the concept can
      successfully describe the pH dependent proton binding and the shift in the
      isoelectric point (IEP) in the presence of variety of monovalent electrolyte
      ions, including Li(+), Na(+), K(+), Cs(+), Cl(-), NO(-)(3), and ClO(-)(4) with a
      common set of parameters. The new concept also sheds more light on the degree of
      hydration of the ions when present as outersphere complexes. Interpretation of
      the charge distribution values obtained shows that Cl(-) ions are located
      relatively close to the surface. The large alkali ions K(+), Cs(+), and Rb(+) are
      at the largest distance. Li(+), Na(+), NO(-)(3), and ClO(-)(4) are present at
      intermediate positions.

PMID- 16085085
TI  - Ternary systems of nonionic surfactant Brij 35, water and various simple
      alcohols: Structural investigations by small-angle X-ray scattering and dynamic
      light scattering.
AB  - Structural properties of ternary systems composed of nonionic surfactant dodecyl
      poly(ethylene oxide-23) ether (C12E23, commercial name: Brij 35), water and
      various alcohols from ethanol to 1-decanol have been investigated using small
      angle X-ray scattering (SAXS) and dynamic light scattering (DLS) techniques. All
      measurements were performed at the temperature 25 degrees C. SAXS experimental
      data were put on absolute scale using water as a secondary standard. The data of
      water-rich mixtures at low to moderate surfactant concentrations were evaluated
      using the generalized indirect Fourier transformation method (GIFT), which is
      based on the simultaneous determination of the intra- and inter-particle
      scattering contributions. In this way, the size and the shape of interacting
      scattering particles in real space could be deduced. The systems with a
      relatively low surfactant concentration (5 mass%) were studied most extensively.
      In these cases, the water-rich regions of the phase diagrams could be
      investigated into more detail, since in the alcohol-rich regions problems with
      the GIFT evaluation of the SAXS data were encountered. The presented results
      demonstrate the level of structural details that can be obtained on the basis of
      scattering methods and point out the specific stages of data evaluation and
      interpretation where one must be extremely precautious. As such they reveal the
      inner structuration of the complex ternary systems of our present interest. In
      parallel, they also indicate that the longer chain alcohols actually behave as
      real oil phases in the studied systems, as one might expect, and also confirm the
      well-known properties of different short to medium chain alcohols that act as co
      solvents and/or co-surfactants in microemulsion systems depending on their chain
      length.

PMID- 16085086
TI  - Modification of fibrous silicates surfaces with organic derivatives: an infrared
      spectroscopic study.
AB  - This contribution explores the interaction of the fibrous silicates,
      palygorskite, sepiolite and chrysotile with a wide range of organic agents.
      Infrared spectroscopy (IR) methods are essential for the characterization of
      solid surfaces and for the investigation of the kind of bonds formed between the
      surface of these silicates and the organic moieties. Thus, when sepiolite or
      palygorskite are treated, e.g., with polyurethanes, alcohols, isocyanates, amines
      or pyridines, specific SiNHC or SiOC bonds are derived from the linkage of the
      differently located OH groups in these fibrous silicates with the organic
      moieties. On the other hand, more stable, covalent SiOSiC bondings are formed
      when the fibrous silicates, especially chrysotile, are reacted with
      heterofunctional silylating agents like chlorosilanes or ethoxysilanes carrying,
      alkyl, alkenyl or aryl groups. Such reactions may occur in the presence or
      absence of HCl. An absorption band at 960 cm(-1)--which we assigned to SiOH
      groups--is detected only in the presence of HCl. The evolution of this band is
      related to the degree of grafting of the organic radicals with the silanol groups
      of the silicates. HCl-generated silanol groups are the main bridges for the
      coupling of organosilyl groups on chrysotile and other silicates by covalent
      bonding, leading the way to the preparation of interesting new materials,
      including fibrous sheet polymers.

PMID- 16085087
TI  - Nutrient absorption by Aphidius ervi larvae.
AB  - It is well documented that in the model system Aphidius ervi Haliday
      (Hymenoptera, Braconidae)/Acyrthosiphon pisum (Harris) (Homoptera, Aphididae)
      host regulation by the parasitoid larva induces in the aphid haemolymph major
      changes of the titer of nutritional compounds such as proteins, acylglycerols and
      free amino acids, in order to meet the stage-specific demands of the developing
      larva. Since little is known about how the larva absorbs these mobilized
      nutritional resources, nutrient absorption by larval stages of A. ervi was
      studied. In 2nd instar larvae, leucine was ten-fold accumulated in the haemocoel,
      and tyrosine and glutamine two-fold. Glucose and fructose were readily absorbed
      and fructose was extensively metabolized by larval tissues. In 3rd instars, the
      presence of a number of larvae that did not ingest the incubation medium enabled
      us to determine the respective amounts of substrate absorbed by the epidermis and
      the midgut. An accumulation of leucine in the haemocoel was observed only when
      midgut cells were involved in absorption, while the amino acid concentration
      within body fluids never exceeded that of the incubation medium when the uptake
      was performed only by epidermal cells. The immunofluorescence analysis, the
      mutual inhibition exerted on labeled glucose or fructose uptakes by a 100-fold
      excess of the sugars and the strong inhibition of uptakes induced by 0.2mM
      cytochalasin B support the expression of facilitative GLUT2-like transporters in
      the apical and basal cell membranes of midgut epithelial cells. Taken together,
      these results prove that both midgut and epidermis are involved in nutrient
      absorption throughout the parasitoid development, that GLUT2 transporters are
      responsible for glucose and fructose uptakes and that the chemical gradient that
      favors the passive influx of the two sugars is maintained by their conversion to
      other substrates.

PMID- 16085089
TI  - Transcranial ultrasound angiography (T USA): a new approach for contrast specific
      imaging of intracranial arteries.
AB  - The goal was to develop an ultrasound contrast agent-specific imaging mode that
      offers an angiography-like view of the intracranial arteries and enables lower
      mechanical index MI settings compared to conventional transcranial duplex
      sonography. We studied 12 patients with transcranial ultrasound angiography (t
      USA) via the temporal bone window after an IV bolus injection of a
      perfluorocarbon-based microbubble contrast agent (Imagent). The aim was to
      display the intracranial vessel segments of the middle cerebral artery (M1, M2
      and M3), the anterior cerebral artery (A1 and A2), the posterior cerebral artery
      (P1, P2 and P3) and the internal carotid artery (C1/2 and C3/4). t USA is a B
      mode phase inversion imaging technique that uses wideband harmonic signals for
      image generation. We demonstrate, in this report, that t USA provides detailed
      anatomical display at native B-mode spatial resolution with fewer artifacts,
      yielding improved delineation of intracranial vessels that are in the 1- to 2-mm
      range.

PMID- 16085090
TI  - Semiquantitative analysis of ultrasonic cerebral perfusion imaging.
AB  - The bolus kinetic in ultrasonic cerebral perfusion imaging is the most favored
      data acquisition and processing technique. However, there has not yet been
      convincing evidence for the potential to (semi-) quantitatively describe
      perfusion. Aim of this study was to determine the intraindividual range of
      relevant perfusion parameters to describe individual physiological cutoff scores.
      In 20 healthy volunteers, cerebral perfusion was evaluated using the bilateral
      approach with phase inversion harmonic imaging and the bolus kinetic. Relevant
      parameters (time-to-peak intensity, TPI; peak width, PW) were derived in 14
      regions-of-interest in both hemispheres. The median and quartile deviation (QD)
      of these values were individually calculated. Within the 20 individuals, the mean
      QD of TPI was 0.68 s, and there was no case in which any TPI exceeded the mean
      more than 2 s. With PW, the mean QD was 1.2 s, and the mean was not exceeded by
      more than 6 s. Intraindividual perfusion parameters, especially TPI, show a
      considerable small range. Thus, the bolus kinetic derives reliable
      semiquantitative information once intraindividual comparison can be accomplished.
      We therefore propose that bilateral examination with the unaffected hemisphere as
      referential region should be performed in acute stroke. Future studies have to
      evaluate the potential of this approach of discriminating ischemia and
      hypoperfusion in the affected hemisphere.

PMID- 16085091
TI  - Hypoechoic areas on ultrasound images of atheroma are not always diagnostic of
      fatty plaque.
AB  - Atherosclerotic plaques in ultrasound (US) images may have bright areas
      suggestive of fibrous plaque and hypoechoic areas that are often interpreted as
      fatty plaque. The current study was designed to test the hypothesis that fibrous
      tissue in atherosclerotic plaques will be hyperechoic or hypoechoic, depending on
      collagen fiber morphology. Twelve segments of aortic arch containing
      atherosclerotic plaques obtained from cadavers were imaged with an 8-MHz US
      transducer, then sectioned, stained with picrosirius red and examined with
      polarized light microscopy. There were 12 bright areas that contained
      predominantly thick collagen fibers. Two areas were anechoic, with predominantly
      thin collagen fibers. There were 11 hypoechoic areas; six of these contained thin
      fibers and five contained no collagen on polarized light microscopy, suggesting
      fat or thrombus. We conclude that fibrous aortic plaques consisting of
      predominantly thin fibers appear hypoechoic or anechoic on US images and,
      therefore, may be indistinguishable from fatty plaques.

PMID- 16085092
TI  - Fatty changes as a misleading factor in the evaluation with ultrasound of
      superficial lymph nodes.
AB  - The object of this paper was to investigate lipoplastic lymphadenopathy in
      superficial locations with ultrasound. We selected 110 patients with a total
      number of 247 nodes with a central hyperechoic area extended for more than one
      third of the transverse diameter. We considered gender, age, body mass index
      (BMI), and associated disease such as thyroid disorders and diabetes. For each
      lymph node, we measured the long:short axis ratio and the parenchyma:fat (P:F)
      ratio. Differences between mean P:F ratio in diabetic and nondiabetic patients
      were significant (p=0.045). Mean P:F ratio was negatively related to BMI (r=0.62,
      p=0.015) and age (r=0.54, p=0.024). All of the nodes examined with a mean P:F
      ratio <or= 1.2 (58) were found in patients older than 72 y and with a BMI higher
      than 27.8. Fatty involution may mimic a macrometastasis at palpation and may
      cause difficulties in US detection.

PMID- 16085093
TI  - Fetal hemodynamics evaluated by Doppler velocimetry in the second half of
      pregnancy.
AB  - The objective of our study was to assess fetal hemodynamics by Doppler
      velocimetry during the second half of pregnancy. We carried out a longitudinal
      study on 33 normal fetuses between the 22nd and 38th weeks of gestation. Doppler
      velocimetry was performed in the aorta, suprarenal (SRA) and infrarenal (IRA)
      segments, middle cerebral artery (MCA) and umbilical artery (UA), on the basis of
      fetal peak systolic velocity (SV), end-diastolic velocity (DV) and resistance
      index (RI). We used a sample volume of 1 mm, a wall filter of 50 to 100 Hz, a 5
      degrees to 19 degrees insonation angle in the MCA and UA, and below 60 degrees in
      the SRA and IRA. Between the 22nd and 38th weeks of gestation, SV and DV
      increased in all fetal arteries (p<0.05), but SV decreased in the UA from 52.5 to
      46.2 cm/s between the 34th and 38th gestational weeks (p<0.05). The RI was
      unchanged in the SRA and throughout most of the gestational weeks in the IRA
      (p>0.05), but decreased from 0.69 to 0.56 in the UA (p<0.05). In the MCA, it
      decreased from 0.85 to 0.75 between the 26th and 38th gestational weeks (p<0.05).
      In conclusion, the volume of blood flow in the fetal organs necessary for their
      development is related to increased SV and DV and to decreased RI. The Doppler
      velocimetry measurements for normal fetuses could be compared with those for
      fetuses in high-risk pregnancies.

PMID- 16085094
TI  - Doppler echocardiography flow-velocity image analysis for patients with atrial
      fibrillation.
AB  - Currently, Doppler echocardiography analysis is performed manually. An automated
      method that analyzes the Doppler signal can potentially improve accuracy and
      result in a powerful tool for noninvasive evaluation of cardiac hemodynamics,
      especially for patients with atrial fibrillation, where multiple samples are
      needed to obtain an accurate averaged measurement. The aim of this study was to
      develop an automated method for Doppler analysis based on image processing and
      computer vision algorithms. Images were obtained from the mitral valve and the
      tricuspid valve Doppler tracings from 45 patients, 20 with normal sinus rhythm
      and 25 with atrial fibrillation. The proposed algorithm automatically detects the
      maximal velocity envelope of the spectral Doppler ultrasound tracings. Averaged
      values for the time velocity integral, peak mitral inflow velocity and peak
      tricuspid regurgitation velocity were calculated for multiple beats available in
      a single screen frame. Measurements extracted automatically from the maximal
      velocity envelope were compared to measurements obtained manually by two expert
      technicians. High linear correlation (r) was found between the automatically- and
      the manually-extracted parameters (0.95 < r < 0.99). A smaller variation was
      found in most cases between the manually-calculated average beat and the
      automated average beat (bias value between 3.8% and 5.2%) than between the
      manually-calculated average beat and the selection of a representative beat (bias
      value between 6.2% and -2.6%). The newly-developed automated method offers a new,
      accurate and reliable clinical tool, particularly for the assessment of patients
      with irregular heart rate.

PMID- 16085095
TI  - Monitoring structural changes in cells with high-frequency ultrasound signal
      statistics.
AB  - We investigate the use of signal envelope statistics to monitor and quantify
      structural changes during cell death using an in vitro cell model. Using a f/2.35
      transducer (center frequency 20 MHz), ultrasound backscatter data were obtained
      from pellets of acute myeloid leukemia cells treated with a DNA-intercolating
      chemotherapy drug, as well as from pellets formed with mixtures of treated and
      untreated cells. Simulations of signals from pellets of mixtures of cells were
      generated as a summation of point scatterers. The signal envelope statistics were
      examined by fitting the Rayleigh and generalized gamma distributions. The fit
      parameters of the generalized gamma distribution showed sensitivity to structural
      changes in the cells. The scale parameter showed a 200% increase (p<0.05) between
      untreated and cells treated for 24 h. The shape parameter showed a 50% increase
      (p<0.05) over 24 h. Experimental results showed reasonable agreement with
      simulations. The results indicate that high-frequency ultrasound signal
      statistics can be used to monitor structural changes within a very low percentage
      of treated cells in a population, raising the possibility of using this technique
      in vivo.

PMID- 16085096
TI  - Empirical mode decomposition and tissue harmonic imaging.
AB  - Empirical mode decomposition (EMD) is a relatively new technique used in the
      analysis of nonlinear and nonstationary time series. Previous signal-processing
      methods used for medical ultrasound have been based on the assumption of a linear
      time-invariant system. More recently, the technique of tissue harmonic imaging
      (THI) has become prevalent. This technique relies on the nonlinear propagation of
      the sound wave through the medium to disperse the signal energy into the harmonic
      frequencies of the transmitted signal. In this paper, results are presented from
      using EMD to process received ultrasound echo signals that have passed through
      nonlinear media. The Hilbert spectrum is used to demonstrate an interpretation of
      the physical process underlying THI that is based on the concept of intrawave
      frequency modulation, rather then the spreading of signal energy into harmonic
      frequencies. The technique of EMD is shown to be able to produce superior results
      to the bandpass filtering method of THI, even when the band width of the
      transducer was such that the second harmonic would be suppressed.

PMID- 16085097
TI  - Absolute measurement of ultrasonic backscatter from single microbubbles.
AB  - Good quality acoustical experiments are needed to measure microbubble behavior.
      An absolute calibration of the transmitted ultrasound field is possible using a
      calibrated hydrophone, but characterization of the received ultrasound beam is a
      more elaborate process and is not described in the literature. A new system based
      on a hydrodynamically focused flow has been used to measure echoes from single
      microbubbles at well specified positions in the ultrasonic field. An experimental
      set-up was built around a commercial scanner (Sonos 5500, Philips Medical
      Systems) to measure the scatter from solid spheres with radii between 30 to 60
      microm. The behavior of these linear scatterers is accurately predicted by theory
      and software was produced to incorporate a simulation of the experimental
      conditions. The calibration of a phased array transducer was achieved by
      quantifying the receiver's spectral sensitivity for the range of receive
      frequencies (1.2 to 4.5 MHz). Examples of echoes from the microbubble agent
      Definity are used to illustrate the implementation of the calibration technique.

PMID- 16085098
TI  - Effects of beam steering in pulsed-wave ultrasound velocity estimation.
AB  - Experimental and computer simulation methods have been used to investigate the
      significance of beam steering as a potential source of error in pulsed-wave flow
      velocity estimation. By simulating a typical linear-array transducer system as
      used for spectral flow estimation, it is shown that beam steering can cause an
      angle offset resulting in a change in the effective beam-flow angle. This offset
      primarily depends on the F-number and the nominal steering angle. For example, at
      an F-number of 3 and a beam-flow angle of 70 degrees , the velocity error changed
      from -5% to + 5% when the steering angle changed from -20 degrees to + 20 degrees
      . Much higher errors can occur at higher beam-flow angles, with smaller F-numbers
      and greater steering. Our experimental study used a clinical ultrasound system, a
      tissue-mimicking phantom and a pulsatile waveform to determine peak flow velocity
      errors for various steering and beam-flow angles. These errors were found to be
      consistent with our simulation results.

PMID- 16085099
TI  - A phantom with reduced complexity for spatial 3-D ultrasound calibration.
AB  - The design of a new phantom for 3-D ultrasound calibration is presented. The
      phantom provides a viable alternative to existing phantoms that are significantly
      more complex and require high precision fabrication. The phantom, referred to as
      a "plane-of-wires" phantom, consists of two wires mounted at the same fixed
      height above the bottom of a water tank. Data collection for calibration involved
      rotating and translating the phantom so that the wires remained in a single plane
      parallel to the tank bottom. The mean reconstruction accuracy of the plane-of
      wires calibration is 0.66 mm at a mean depth of 12.3 mm, with a precision of 1.23
      mm at the same mean depth. The calibration was used to determine the volume of a
      cube with known volume with an error of 2.51%. The calibration performance
      achieved is comparable with that of existing approaches.

PMID- 16085100
TI  - Comparison of calibration methods for spatial tracking of a 3-D ultrasound probe.
AB  - Real-time 3-D ultrasound (US) is a new-generation US system that uses a dedicated
      probe to create volume data sets instead of standard 2-D cross-sectional images.
      For applications in image-guided surgery and radiation therapy, a position
      tracker is added to the probe so that the volumes can be located in space.
      Calibration plays a critical role in determining the overall accuracy of an US
      volume-tracking system. In this paper, three calibration methods are developed
      specifically for 3-D probes. The three methods are based on a IXI-shaped wire
      phantom, a cube phantom and a stylus. The performance of each method was
      evaluated in terms of calibration reproducibility, point accuracy and
      reconstruction accuracy by distance measurement. The mean errors in the
      reproducibility tests were 1.50 mm (IXI-wire), 1.16 mm (cube) and 5.13 mm
      (stylus). The root mean square errors of the point accuracy measure were 2.15 mm
      (IXI-wire), 4.91 mm (cube) and 2.36 mm (stylus). The root mean square errors of
      the reconstruction accuracy by distance measure were 1.52 mm (IXI-wire), 1.59 mm
      (cube) and 1.85 mm (stylus). Overall, the IXI-wire phantom achieved the best
      results.

PMID- 16085101
TI  - Investigation of parametric spectral estimation techniques for elasticity
      imaging.
AB  - Several autoregressive (AR) and autoregressive moving average (ARMA) parametric
      spectral estimators were evaluated for use in tissue strain estimation. Using
      both 1-D simulations and in vitro phantom experiments, the performance of these
      parametric spectral strain estimators were compared against both a nonparametric
      discrete Fourier transform (DFT) spectral strain estimator and a coherent
      elastographic technique. Parametric spectral estimator model orders were selected
      based on a modified strain filter approach. This technique illustrated the trade
      offs between different signal-processing parameters and a strain estimator
      performance measure, namely the area under the strain filter (using applied
      strain dynamic range of 0.1 to 50%). The Yule-Walker AR spectral strain estimator
      outperformed all other parametric methods evaluated, but failed to outperform the
      DFT-based approach. Furthermore, both these spectral strain-estimation techniques
      exhibit an elastographic signal-to-noise ratio (SNR(e)) and strain estimation
      dynamic range not achievable using conventional elastography without global
      stretching.

PMID- 16085102
TI  - Acoustic cavitation in phacoemulsification and the role of antioxidants.
AB  - Cataract surgery by phacoemulsification generates acoustic cavitation, resulting
      in formation of reactive oxygen species. The aim of this study was to establish
      the mechanism of damage by phacoemulsification in an in vitro setting simulating
      cataract surgery and to assess the protective effects of water-soluble
      antioxidants. Electron paramagnetic resonance spectroscopy was used to analyze
      generation of radicals in an intraocular irrigating solution by
      phacoemulsification instrumentation, operating at an ultrasonic frequency range
      of 40--60 kHz. Hydroxyl radicals were generated by phacoemulsification under
      conditions simulating cataract surgery. The effects of water-soluble antioxidants
      in the irrigating solution on the amounts of radicals were evaluated by electron
      paramagnetic resonance spectroscopy. The water-soluble antioxidant glutathione,
      applied in either oxidized or reduced form, decreased hydroxyl radicals
      concentration measured in the sonicated medium. The effective concentrations of
      oxidized and reduced glutathione in irrigating solution that significantly
      eliminate the hydroxyl radical signal were determined in the range of 10(-3)-10(
      2) M. Antioxidants should be applied clinically to reduce damage to the corneal
      endothelium induced by phacoemulsification, thereby improving biosafety.

PMID- 16085103
TI  - Involvement of adenosine 5'-triphosphate in ultrasound-induced fracture repair.
AB  - Ultrasound (US) accelerates fracture healing; however, the mechanism of this
      effect remains unclear. Adenosine 5'-triphosphate (ATP) stimulates bone
      remodeling and is released constitutively from intact osteoblasts; this is a
      process that is enhanced after mechanical stimulation. We hypothesized that ATP
      release from osteoblasts is increased after US stimulation and that this leads to
      accelerated fracture healing. US was applied to SaOS-2 human osteoblasts and the
      concentration of ATP in the cell culture medium was determined. Cell
      proliferation and gene expression were subsequently investigated. Increased
      concentrations of ATP were detected in the culture medium of US-treated cells and
      both ATP and US stimulation caused increased receptor activator of nuclear factor
      kappa B ligand (RANKL), decreased osteoprotegerin expression and increased cell
      proliferation by SaOS-2 cells. These findings indicate that US causes ATP release
      by osteoblasts in vitro and that this may contribute to accelerated fracture
      healing by enhancing osteoblast proliferation and increasing RANKL expression and
      decreasing osteoprotegerin expression by osteoblasts to promote
      osteoclastogenesis.

PMID- 16085104
TI  - Metabolic clearance of the antioxidant ascorbic acid in surgical patients.
AB  - BACKGROUND: A reduction of plasma ascorbic acid concentration in the post
      operative period has been well documented and is associated with an increase in
      post-operative complications. The underlying reason for the decreased
      concentration of ascorbic acid in the plasma is not clear. However, only an
      increased post-operative requirement for ascorbic acid would justify a
      substitution. Therefore, we investigated the pre-operative and post-operative
      metabolic clearance of ascorbic acid. MATERIALS AND METHODS: We calculated the
      metabolic clearance subsequent to intravenous bolus injection of 6 mg ascorbic
      acid/kg body weight in 15 patients before and after they underwent major
      maxillofacial surgery. Blood samples were taken before and 5, 15, 30, 45, 60, 90,
      120, and 240 min after administration of ascorbic acid before and after the
      operation. Urine was collected. Ascorbic acid in plasma and urine was analyzed
      using a high performance liquid chromatographic technique. RESULTS: The pre
      operative metabolic clearance was 7.6 +/- 2.22 l/h (mean +/- SD), increasing
      significantly to 12.1 +/- 4.87 l/h on the first post-operative day (P < 0.001).
      Doses of approximately 1150 mg ascorbic acid would be necessary to compensate for
      the observed loss and to raise plasma ascorbic acid to high normal values.
      CONCLUSIONS: There is a significantly increased post-operative metabolic
      clearance of ascorbic acid that might be considered when framing future dose
      recommendations in post-operative patients.

PMID- 16085105
TI  - Risk taking and tolerance of uncertainty: implications for surgeons.
AB  - BACKGROUND: Adherence to evidence-based adverse outcome prevention techniques is
      a critical factor in providing high-quality patient care, but many of these
      interventions are not used by physicians. It is unclear if surgeons' risk
      attitudes and reactions to uncertainty influence their use of these or other
      interventions. MATERIALS AND METHODS: A systematic review of the literature was
      conducted to identify studies evaluating the effects of physicians' risk
      attitudes, reactions to uncertainty or ambiguity, and personality traits on
      clinical decision making. RESULTS: A variety of instruments to assess risk
      attitude and reactions to uncertainty have been developed and tested among
      physicians involved in critical care and emergency medicine. Scoring systems
      distinguish risk averse and risk seeking practitioners. In many studies, these
      characteristics were related to clinical decision making in situations of
      uncertainty. For example, among patients evaluated in the emergency room for
      chest pain, "risk-seeking" physicians admitted significantly fewer patients who
      did not have acute myocardial infarction than risk-avoiding physicians (29% and
      47% of patients admitted, respectively). In contrast, risk-seeking physicians
      were no more likely to discharge a patient who eventually was found to have an
      acute myocardial infarction. CONCLUSIONS: There are very limited data on the
      extent to which surgical decision making is linked to risk taking behavior and
      "comfort with uncertainty". Understanding the behaviors, attitudes and beliefs
      that make up surgical "judgment" remains a challenge for those interested in
      influencing behavior.

PMID- 16085106
TI  - Alternative pathways as mechanism for the negative effects associated with
      overexpression of superoxide dismutase.
AB  - One of the most important antioxidant enzymes is superoxide dismutase (SOD),
      which catalyses the dismutation of superoxide radicals to hydrogen peroxide. The
      enzyme plays an important role in diseases like trisomy 21 and also in theories
      of the mechanisms of aging. But instead of being beneficial, intensified
      oxidative stress is associated with the increased expression of SOD and also
      studies on bacteria and transgenic animals show that high levels of SOD actually
      lead to increased lipid peroxidation and hypersensitivity to oxidative stress.
      Using mathematical models we investigate the question how overexpression of SOD
      can lead to increased oxidative stress, although it is an antioxidant enzyme. We
      consider the following possibilities that have been proposed in the literature:
      (i) Reaction of H(2)O(2) with CuZnSOD leading to hydroxyl radical formation. (ii)
      Superoxide radicals might reduce membrane damage by acting as radical chain
      breaker. (iii) While detoxifying superoxide radicals SOD cycles between a reduced
      and oxidized state. At low superoxide levels the intermediates might interact
      with other redox partners and increase the superoxide reductase (SOR) activity of
      SOD. This short-circuiting of the SOD cycle could lead to an increased hydrogen
      peroxide production. We find that only one of the proposed mechanisms is under
      certain circumstances able to explain the increased oxidative stress caused by
      SOD. But furthermore we identified an additional mechanism that is of more
      general nature and might be a common basis for the experimental findings. We call
      it the alternative pathway mechanism.

PMID- 16085107
TI  - Epidemiology and disease-control under gene-for-gene plant-pathogen interaction.
AB  - An introduction of disease-resistant variety of a crop plant often leads to the
      development of a virulent race in pathogen species that restores the
      pathogenicity to the resistant crop. This often makes disease control of crop
      plants extremely difficult. In this paper, we theoretically explore the optimal
      'multiline' control, which makes use of several different resistant varieties,
      that minimizes the expected degree of crop damages caused by epidemic outbreaks
      of the pathogen. We examine both single-locus and two-locus gene-for-gene (GFG)
      systems for the compatibility relationship between host genotypes and pathogen
      genotypes, in which host haplotype has either susceptible or resistant allele in
      each resistance locus, and the pathogen haplotype has either avirulent or
      virulent allele in the corresponding virulence locus. We then study the optimal
      planting strategy of host resistant genotypes based on standard epidemiological
      dynamics with pathogen spore stages. The most striking result of our single-locus
      GFG model is that there exists an intermediate optimum mixing ratio for the
      susceptible and resistant crops that maximizes the final yield, in spite of the
      fact that the susceptible crop has no use to fight against either avirulent or
      virulent race of the pathogen. The intermediate mixture is optimum except when
      the initial pathogen spore population in the season consists exclusively of the
      virulent race. The optimal proportion of resistant crops is approximately 1/R(0),
      where R(0) is the basic reproductive ratio of pathogen--the rest (the vast
      majority if R(0) is large) of crops should be the susceptible genotype. By mixing
      susceptible and resistant crops, we can force the pathogen races to compete with
      each other for their available hosts. This competition between avirulent and
      virulent races prevents the fatal outbreak of the virulent race (the super-race)
      that can infect all the host genotypes. In the two-locus GFG control, there again
      exists the optimal mixing ratio for the fraction of universally susceptible
      genotype and the total fraction of various resistant genotypes, with the ratio
      close to 1/R(0).

PMID- 16085108
TI  - Does foraging adaptation create the positive complexity-stability relationship in
      realistic food-web structure?
AB  - The adaptive food-web hypothesis suggests that an adaptive foraging switch
      inverses the classically negative complexity-stability relationships of food webs
      into positive ones, providing a possible resolution for the long-standing paradox
      of how populations persist in a complex natural food web. However, its
      applicability to natural ecosystems has been questioned, because the positive
      relationship does not emerge when a niche model, a realistic "benchmark" of food
      web models, is used. I hypothesize that, in the niche model, increasing
      connectance influences the fraction of basal species to destabilize the system
      and this masks the inversion of the negative complexity-stability relationship in
      the presence of adaptive foraging. A model analysis shows that, if this
      confounding effect is eliminated, then, even in a niche model, a population is
      more likely to persist in a more complex food web. This result supports the
      robustness of adaptive food-web hypothesis and reveals the condition in which the
      hypothesis should be tested.

PMID- 16085109
TI  - Role of potassium lateral diffusion in non-synaptic epilepsy: a computational
      study.
AB  - An increase of extracellular potassium ion concentration can result in neuronal
      hyperexcitability, and thus contribute to non-synaptic epileptiform activity. It
      has been shown that potassium lateral diffusion alone is sufficient for
      synchronization in the low-calcium epilepsy in-vitro model. However, it is not
      yet known whether the lateral diffusion can, by itself, induce seizure activity.
      We hypothesize that spontaneous sustained neuronal activity can be generated by
      potassium coupling between neurons. To test this hypothesis, neuronal simulations
      with 2-cell or 4-cell models were used. Each model neuron was embedded in a bath
      of K+ and surrounded by interstitial space. Interstitial potassium concentration
      was regulated by both K+-pump and glial buffer mechanisms. Simulations performed
      with two coupled neurons with parameter values within physiological range show
      that, without chemical and electrical synapses, potassium lateral diffusion alone
      can generate and synchronize zero-Ca2+ non-synaptic epileptiform activity.
      Simulations performed with a network of four zero-Ca2+ CA1 pyramidal neurons
      modeled in zero-calcium conditions also show that spontaneous sustained activity
      can propagate by potassium lateral diffusion alone with a velocity of
      approximately 0.93 mm/sec. This diffusion model used for the simulations is based
      on physiological parameters, is robust for various kinetics, and is able to
      reproduce both the spontaneous triplet bursting of non-synaptic activity and
      speed of propagation in low-Ca2+ non-synaptic epilepsy experiments. These
      simulations suggest that potassium lateral diffusion can play an important role
      in the synchronization and generation on non-synaptic epilepsy.

PMID- 16085110
TI  - Benthic invasive pests in Uruguay: a new problem or an old one recently
      perceived?

PMID- 16085111
TI  - Inter- and intra-annual variations of Pb/Ca ratios in clam shells (Mercenaria
      mercenaria): a record of anthropogenic lead pollution?
AB  - In this study, we re-assess the use of bivalve shells as a proxy of lead
      pollution. Previous studies have stressed that shells display little variability
      compared to soft tissues and thus are better for pollution biomonitoring.
      However, in this manuscript we illustrate that there is large inter- and intra
      annual Pb variability between shells of the clam Mercenaria mercenaria collected
      in North Carolina, USA. Therefore, year to year, as well as intra-annual
      variations in Pb/Ca ratios should be interpreted with caution. Despite this
      variability, we were able to obtain an annual Pb chronology from 1949 to 2002
      using 11 shells collected at different times which clearly exhibited the late
      1970's peak in Pb from leaded gasoline use. This indicates that when enough
      specimens are pooled together, bivalve shells can be used to reconstruct large,
      long term changes in environmental Pb concentrations. Our data compare well with
      other studies of aragonite clams from sites with low regional lead pollution.
      From this we conclude that the Cape Lookout region of North Carolina has not
      received extensive pollution over the 1949-2002 period. The Pb concentration in
      shells growing in the 1949-1976 period was not significantly different from those
      growing in the 1982-2002 period, although other proxies suggest that the 1949
      1976 period should be considerably higher. Therefore, our data suggest that there
      is still a modern low-level source of Pb in the coastal North Carolina
      environment.

PMID- 16085112
TI  - Introduction: matrix biology in the 21st century. From a static-rheological role
      to a dynamic-signaling function.
AB  - These introductory remarks contain a succinct reminder of the developmental
      history of matrix biology, from the descriptive biochemistry of connective
      tissues to the up to date cell biology of extracellular matrices. The rapid
      growth of this discipline makes it prohibitive to give a complete coverage of
      recent results on all aspects of matrix biology and pathology. The articles in
      this special issue concern several of the ECM-macromolecules and some of their
      functional characteristics. No space remained for reviews on matrix related
      pathologies. As a partial compensation some recent aspects of cell-cell and cell
      matrix interactions in malignant growth are mentioned in this introduction.

PMID- 16085113
TI  - Hyaluronan metabolism: a major paradox in cancer biology.
AB  - Paradoxically, both hyaluronan (HA) and hyaluronidases, the enzymes that
      eliminate HA, can correlate with cancer progression. Levels of HA on the surface
      of tumor cells are indicators of poor outcome. Certain hyaluronidases, products
      of tumor suppressor genes eliminated in the course of tumor spread, are used
      clinically in anti-cancer chemotherapy regimens. Such information would indicate
      that cancer progression is inhibited by hyaluronidase. Yet progression of certain
      cancers correlates with levels of hyaluronidase activity. An attempt is made here
      to understand such apparent contradictions by examining details of HA metabolism.
      Anabolic and catabolic pathways are comprised of the HA synthases and
      hyaluronidases, respectively. There are several enzymes that synthesize HA, each
      under a different control mechanism, generating products of differing polymer
      size. The hyaluronidases degrade HA in step-wise fashion, the polymer decreasing
      in size in quantum steps, each size-specific polymer having a different
      biological activity. Superimposed on these are the potent hyaluronidase
      inhibitors, about which very little is known. These components of HA metabolism
      are reviewed here for possible roles in supporting or suppressing malignant
      transformation, growth, invasion and metastatic spread of tumors. Such a
      systematic approach may reveal mechanisms used in the course of cancer
      progression, resolve some of the apparent disparities, render new prognostic
      markers, and provide new targets for therapeutic intervention.

PMID- 16085114
TI  - The dissection of human tropoelastin: from the molecular structure to the self
      assembly to the elasticity mechanism.
AB  - After a historical introduction the authors describe their most recent results on
      the structure, assembly and elasticity of elastin. Recent results obtained by
      analyzing the conformation of polypeptide sequences encoded by the single exons
      of human tropoelastin demonstrated the presence of labile conformations such as
      poly-proline II helix (PPII) and beta-turns whose stability is strongly dependent
      on the microenvironment. Stable, periodic structures, such as alpha-helices, are
      only present in the poly-alanine cross-linking domains. These findings give a
      strong experimental basis to the understanding of the molecular mechanism of
      elasticity of elastin. In particular, they strongly support the description of
      the native relaxed state of the protein in terms of trans-conformational
      equilibria between extended and folded structures as previously proposed [Int. J.
      Biochem. Cell. Biol. 31 (1999) 261]. The same polypeptide sequences have been
      analyzed for their ability to coacervate and to self-assembly. Although the great
      majority of them were shown to be able to adopt more or less organized
      structures, only a few were indeed able to coacervate. Studies carried out by
      transmission electron microscopy showed the polypeptides to adopt a variety of
      supramolecular structures going from a filamentous organization (typical of
      elastin) to amyloid-like fibers. On the whole, the results obtained gave
      significant insight to the roles played by specific polypeptide sequences in self
      assembly and possibly in elasticity.

PMID- 16085115
TI  - Cellular interactions with elastin.
AB  - Elastin is a key structural component of the extracellular matrix. Tropoelastin
      is the soluble precursor of elastin. In addition to providing elastic recoil to
      various tissues such as the aorta and lung, elastin, tropoelastin and elastin
      degradation products are able to influence cell function and promote cellular
      responses. These responses include chemotaxis, proliferation and cell adhesion.
      The interaction of elastin products with cells has been attributed to the elastin
      receptor. However, additional cell-surface receptors have also been identified.
      These include G protein-coupled receptors and integrins. The potential roles of
      these receptors in cell-elastin interactions, with particular focus on elastin
      formation are discussed.

PMID- 16085116
TI  - Cell-elastin interaction and signaling.
AB  - Matrix biology expanded its sphere of interest over the recent decades from its
      original rheological-morphological functions to incorporate control of cell
      phenotype during development and maturation. Aging and age-related pathologies
      are accompanied by matrix remodeling, loss of phenotypic traits as during
      atherogenesis or tumor growth. Most of these recently discovered functions are
      related to signaling by matrix components to cells through cell-membrane
      receptors. Some of the signaling molecules are produced by proteolytic
      degradation of macromolecules of the extracellular matrix. Such peptides
      (matrikins or matricryptins) exhibit biological functions absent in the native
      molecule from which these peptides were derived. Some of these novel activities
      are potentially harmful and appear to be involved in the age-dependent
      alterations of tissue structure and functions as well as in related pathologies.

PMID- 16085117
TI  - Fibronectin type II (FnII)-like modules regulate gelatinase A activity.
AB  - Gelatinase A, a member of the matrix metalloproteinase family, contains three
      fibronectin type II (FnII)-like modules that are inserted within its catalytic
      domain. These FnII modules, defined as exosites, play an essential role in
      targeting the enzyme to matrix macromolecules, a process which can down-regulate
      membrane-type metalloproteinase-driven progelatinase A activation. The
      exosite/substrate-directed gelatinase inhibitors has been proposed as an
      alternative approach to disappointing active site-directed inhibitors, to control
      gelatinase A activity. In preliminary experiments, we evidenced that long-chain
      unsaturated fatty acids could bind preferentially to the first FnII module of
      gelatinase A. This interaction inhibits the activity of this enzyme towards
      proteins (type I gelatin and collagen) and an octapeptide substrate, with K(i) in
      the micromolar range. Since gelatinase A-catalyzed matrix proteolysis might
      display a positive or negative influence (depending on the substrate cleaved),
      the design of exosite-specific compounds for noncatalytic targeting of gelatinase
      A would necessitate an extensive degradomic analysis.

PMID- 16085118
TI  - Effect of procyanidolic oligomers of Vitis vinifera on the biosynthesis and
      excretion of corneal glycosaminoglycans.
AB  - Glycosaminoglycans (GAG) as hyaluronan and proteoglycans (PG) as dermatan sulfate
      (DSPG) and keratan sulfate (KSPG) play important role in the structure and
      physiological functions of cornea. Several corneal pathologies are associated
      with qualitative and quantitative alterations of GAG and/or PG biosynthesis. For
      these reasons we investigated the effect of procyanidolic oligomers (PCO) on the
      biosynthesis and excretion of GAG-s in bovine corneal explant cultures. This was
      accomplished by the determination of their chemical components, hexoses,
      hexosamines and uronic acids as well as the incorporation of (35)S-sulfate in the
      presence and without PCO in the culture medium. In presence of 1 mg/ml PCO total
      hexoses, hexosamines and uronic acids increased at 5 and 24 h of incubation,
      hexoses less than the two other components. Stimulation of biosynthesis concerned
      essentially the uronic acid containing GAG-s, DS and hyaluronan. (35)S-sulfate
      incorporation decreased in presence of PCO, showing a decreased sulfation of GAG
      s. The most striking effect was however the strongly increased excretion of
      neosynthesized GAG-s in the culture medium. This effect could be beneficial in
      decreasing corneal hydration in inflammatory conditions, together with the
      previously demonstrated protection of corneal macromolecules against proteolytic
      degradation.

PMID- 16085119
TI  - Elastin peptides induced oxidation of LDL by phagocytic cells.
AB  - The degradation products of one of the major component of vascular wall, elastin,
      have several important biological activities. Elastin peptides (KE) are mostly
      generated during vascular aging and the atherosclerotic process. They induce free
      radical and proteases production from cells, which are the major components of
      the atherosclerotic process. In the present study, we investigated whether the
      interaction between elastin peptides and neutrophils as well as monocytes
      contributes to low density lipoproteins (LDL) oxidation, being one of the most
      important initiator of the chronic inflammatory process contributing to the
      development of atherosclerosis. Here, we present data on the link between the
      elastin degradation products and LDL oxidation by the chemotactically attracted
      neutrophils and monocytes. The KE as well as the active epitope, the hexapeptide
      VGVAPG is able, in a differential concentration and time dependence, to induce
      the oxidation of LDL. KE is able to induce via the production of free radicals by
      neutrophils the oxidation of LDL very rapidly and in higher concentration
      compared to monocytes. These effects of KE are occurring through the stimulation
      of the 67 kDa elastin-laminin receptor (ELR), as demonstrated by the uncoupling
      effect of lactose. In our present study, the HDL was able to decrease the LDL
      oxidation by KE. This is a new mechanism by which elastin peptides might
      participate in the initiation and progression of the atherosclerotic process.

PMID- 16085120
TI  - MMP-type endopeptidase activity in the cornea. Its evolution during organ culture
      storage at the Eye Bank. Effect of hyaluronan.
AB  - About 46% of total corneas obtained from donors in the French Eye Bank cannot be
      grafted for several reasons as loss of endothelium or other. Corneal cells
      express proteolytic enzymes, essentially matrix metallo-proteinase MMP-2 and MMP
      9. In presence of hyaluronan and some other GAG-s their activity increases as
      could be shown on keratocyte cultures. Hyaluronan concentration increases during
      in vitro preservation and can represent a serious hazard for corneal
      conservation. The control of MMP-release and activation might well be one of the
      factors involved in graft deterioration. We could show however that only a slight
      fraction (< or =12%) of total, relatively high endopeptidase activity of the
      cornea is released in the media during storing. It appears therefore that most of
      the proteolytic activity determined in corneal extracts remains confined to the
      stroma and might not represent an important risk for preservation, at least for
      the endothelium.

PMID- 16085121
TI  - The collagen superfamily: from the extracellular matrix to the cell membrane.
AB  - The collagen superfamily is highly complex and shows a remarkable diversity in
      molecular and supramolecular organization, tissue distribution and function.
      However, all its members share a common structural feature, the presence of at
      least one triple-helical domain, which corresponds to a number of (Gly-X-Y)n
      repeats (X being frequently proline and Y hydroxyproline) in the amino acid
      sequence. Several sub-families have been determined according to sequence
      homologies and to similarities in the structural organization and supramolecular
      assembly. In the present review, we focus on the newly described fibrillar
      collagens, fibrillar-associated collagens with interrupted triple helix, membrane
      collagens and multiplexins. Recent advances in the characterization of proteins
      containing triple-helical domains but not referred to as collagens are also
      discussed.

PMID- 16085122
TI  - Decreased circulating elastin peptide levels in humans with sepsis.
AB  - OBJECTIVE: Sepsis is a potentially life-threatening medical condition induced by
      viral, bacterial or fungal infection, which is characterized by systemic
      inflammation, hypotension and vasodilation that can lead to cardiovascular
      collapse. Increased activity of elastases, enzymes which degrade the
      extracellular matrix components including elastin, has been demonstrated in
      plasma of septic patients. Since elastin peptides (EP), by binding to an elastin
      laminin receptor on vascular endothelial and smooth muscle cells, induce dose
      dependent vasodilation, we hypothesized that elevated circulating EP could
      contribute to the vasodilation that occurs in septic patients. MATERIALS AND
      METHODS: Blood for measurement of EP was collected from not-septic and septic
      patients admitted to the intensive care unit (ICU), as well as from healthy
      subjects. Plasma EP concentrations were measured using a competitive ELISA
      technique. RESULTS: The plasma EP level in the septic patients was approximately
      half that of the not-septic patients and the healthy controls, with similar EP
      levels in the latter two groups. There was no apparent association between EP
      levels and age or gender in any of the groups. CONCLUSIONS: Plasma EP levels were
      actually decreased in septic patients, possibly indicating that the balance
      between EP production vs. elimination favors elimination. This result further
      suggests that circulating EP may not be important in the development of the
      vasodilation and hypotension that occurs in septic shock. Alternatively, however,
      increased degradation of EP by elastase or other enzymes could lead to the
      appearance of biologically active EP, which may not be recognized by the ELISA
      assay.

PMID- 16085123
TI  - Lysyl oxidase in development, aging and pathologies of the skin.
AB  - Lysyl oxidase (LOX) is a copper- and lysyl-tyrosyl cofactor containing amine
      oxidase that has been known to play a critical role in the catalysis of lysine
      derived crosslinks in extracellular matrix (ECM) proteins in the dermis. Changes
      in the composition and crosslinked state of the ECM and alterations in LOX
      synthesis and activity are known to be associated with aging and a range of
      acquired and heritable skin disorders. It has been assumed until recently that
      the LOX-related changes in the skin are mediated through the catalytic activity
      of LOX. However, work by several laboratories over the last few years has shown
      that LOX is a multifunctional protein. In this review we discuss the regulation
      of expression, localization and activation of LOX in the normal developing and
      adult skin, and alterations in LOX expression and activity associated with skin
      aging and senescence, and in pathological conditions, including wound healing,
      fibrosis, hypertrophic scarring, keloids, scleroderma, and diabetic skin. We
      further evaluate the role of LOX in skin ECM changes associated with the normal
      aging process and with these pathological states. In addition to collagen and
      elastin cross-linkages, regulatory and activation mechanisms and cell type
      specific LOX interactions may contribute to a range of novel intra- and
      extracellular LOX functions that appear critical determinants of the cellular
      microenvironment in the normal skin and in these skin disorders.

PMID- 16085124
TI  - A buccal cell model comet assay: development and evaluation for human
      biomonitoring and nutritional studies.
AB  - The comet assay is a widely used biomonitoring tool for DNA damage. The most
      commonly used cells in human studies are lymphocytes. There is an urgent need to
      find an alternative target human cell that can be collected from normal subjects
      with minimal invasion. There are some reports of buccal cells, collected easily
      from the inside of the mouth, being used in studies of DNA damage and repair, and
      these were of interest. However, our preliminary studies following the published
      protocol showed that buccal cells sustained massive damage and disintegrated at
      the high pH [O. Ostling, K.J. Johanson. Microelectrophoretic study of radiation
      induced DNA damages in individual mammalian cells. Biochem. Biophys. Res. Commun.
      123 (1984) 291-298] used, but that at lower pH were extremely resistant to lysis,
      an essential step in the comet assay. Therefore, the aims of this study were to
      develop a protocol than enabled buccal cell lysis and DNA damage testing in the
      comet assay, and to use the model to evaluate the potential use of the buccal
      cell model in human biomonitoring and nutritional study. Specifically, we aimed
      to investigate intra- and inter-individual differences in buccal cell DNA damage
      (as strand breaks), the effect of in vitro exposure to both a standard oxidant
      challenge and antioxidant treatment, as well as in situ exposure to an
      antioxidant-rich beverage and supplementation-related effects using a carotenoid
      rich food. Successful lysis was achieved using 0.25% trypsin for 30 min followed
      by proteinase K (1mg/ml) treatment for 60 min. When this procedure was performed
      on cells pre-embedded in agarose on a microscope slide, followed by
      electrophoresis (in 0.01 M NaOH, 1mM EDTA, pH 9.1, 18 min at 12 V), a
      satisfactory comet image was obtained, though inter-individual variation was
      quite wide. Pre-lysis exposure of cells to a standard oxidant challenge (induced
      by H2O2) increased DNA strand breaks in a dose related manner, and incubation of
      cells in Trolox (a water soluble Vitamin E analogue) conferred significant
      protection (P<0.05) against subsequent oxidant challenge. Exposure of buccal cell
      in situ (i.e. in the mouth) to antioxidant-rich green tea led to an acute
      decrease in basal DNA strand breaks. In a controlled human intervention trial,
      buccal cells from 14 subjects after 28 days' supplementation with a carotenoid
      rich berry (Fructus barbarum L.) showed a small but statistically significant
      (P<0.05) decrease in DNA strand breaks. These data indicate that this buccal cell
      comet assay is a feasible and potentially useful alternative tool to the usual
      lymphocyte model in human biomonitoring and nutritional work.

PMID- 16085125
TI  - Antioxidants prevent oxidative DNA damage and cellular transformation elicited by
      the over-expression of c-MYC.
AB  - Reactive oxygen species (ROS)-induced genomic damage may have important
      consequences in the initiation and progression of cancer. Deregulated expression
      of the proto-oncogene c-MYC is associated with intracellular oxidative stress and
      increased DNA damage. However, the protective role of antioxidants such as
      Vitamin C against MYC-induced genomic damage has not been fully investigated. In
      a variety of cell lines, we show that ectopic MYC over-expression results in the
      elevation of intracellular ROS levels and a concomitant increase in oxidative DNA
      damage, as assessed by levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG)
      in the genomic DNA. Loading cells with ascorbic acid (AA) relieved MYC-elicited
      intracellular oxidative stress and conferred genomic protection. A
      mitochondrially targeted Vitamin E analog, TPPB, also protected cells from MYC
      elicited oxidative DNA damage, suggesting the involvement of mitochondria in
      increased ROS production. We found that deregulated MYC expression resulted in
      the attenuation of intracellular glutathione levels, which was reversed by
      loading cells with Vitamin C. Additionally, cells over-expressing MYC had
      elevated levels of intracellular superoxide, which was significantly quenched by
      Vitamin C or the selective superoxide quencher, Tiron. Consequently, Vitamin C
      and other antioxidants protected cells from MYC-induced cellular transformation.
      Our studies implicate a role for ROS, and superoxide in particular, in MYC
      elicited oxidative DNA damage and cellular transformation, and point to a
      pharmacological role of antioxidants in cancer chemoprevention.

PMID- 16085126
TI  - Oxidative stress-induced DNA damage by particulate air pollution.
AB  - Exposure to ambient air particulate matter (PM) is associated with pulmonary and
      cardiovascular diseases and cancer. The mechanisms of PM-induced health effects
      are believed to involve inflammation and oxidative stress. The oxidative stress
      mediated by PM may arise from direct generation of reactive oxygen species from
      the surface of particles, soluble compounds such as transition metals or organic
      compounds, altered function of mitochondria or NADPH-oxidase, and activation of
      inflammatory cells capable of generating ROS and reactive nitrogen species.
      Resulting oxidative DNA damage may be implicated in cancer risk and may serve as
      marker for oxidative stress relevant for other ailments caused by particulate air
      pollution. There is overwhelming evidence from animal experimental models, cell
      culture experiments, and cell free systems that exposure to diesel exhaust and
      diesel exhaust particles causes oxidative DNA damage. Similarly, various
      preparations of ambient air PM induce oxidative DNA damage in in vitro systems,
      whereas in vivo studies are scarce. Studies with various model/surrogate particle
      preparations, such as carbon black, suggest that the surface area is the most
      important determinant of effect for ultrafine particles (diameter less than 100
      nm), whereas chemical composition may be more important for larger particles. The
      knowledge concerning mechanisms of action of PM has prompted the use of markers
      of oxidative stress and DNA damage for human biomonitoring in relation to ambient
      air. By means of personal monitoring and biomarkers a few studies have attempted
      to characterize individual exposure, explore mechanisms and identify significant
      sources to size fractions of ambient air PM with respect to relevant biological
      effects. In these studies guanine oxidation in DNA has been correlated with
      exposure to PM(2.5) and ultrafine particles outdoor and indoor. Oxidative stress
      induced DNA damage appears to an important mechanism of action of urban
      particulate air pollution. Related biomarkers and personal monitoring may be
      useful tools for risk characterization.

PMID- 16085127
TI  - A mouse model of the fragile gene FHIT: From carcinogenesis to gene therapy and
      cancer prevention.
AB  - Mouse models of tumor suppressors are increasingly useful to investigate
      biomedical aspects of cancer genetics. Some tumor suppressor genes are located at
      common fragile sites that are specific chromosomal regions highly susceptible to
      DNA lesions. The tumor suppressor gene FHIT, at the fragile site FRA3B, is the
      first fragile gene with a developed and characterized mouse knockout model. The
      human gene FHIT is frequently deleted in cancers and cancer cell lines of many
      epithelial tissues, and Fhit protein is absent or reduced in most cancers. The
      mouse Fhit ortholog is also located at a common fragile site, Fra14A2 on murine
      chromosome 14, and sustains homozygous deletions in murine cancer cell lines. The
      Fhit knockout mouse is, therefore, an adequate model to study human FHIT
      function. To establish an animal model and to explore the role of FHIT in
      tumorigenesis, we have developed a mouse strain carrying one or two inactivated
      Fhit alleles. Insights into Fhit mouse genetics that have emerged in the last 7
      years, and are reviewed in the present article, allowed for development of new
      tools in carcinogenesis and gene delivery studies.

PMID- 16085128
TI  - Evaluative conditioning is intact after unilateral resection of the anterior
      temporal lobe in humans.
AB  - Several lesion and functional imaging studies conducted in animals and humans
      suggest that structures within the amygdaloid nuclear complex (ANC) are important
      for the occurrence of fear conditioning. Whether this brain structure is also
      critical for evaluative conditioning, has been investigated less frequently. In
      the current experiment, a group of participants with unilateral resection of the
      anterior temporal lobe and a control group received a differential evaluative
      flavor-taste conditioning task. In the pre-acquisition phase, two fruit flavors
      (the conditioned stimuli (CSs)) were presented and participants were instructed
      to evaluate both. In the subsequent acquisition phase, one of these fruit flavors
      (CS+) was presented together with a bad tasting substance Tween20 (polysorbate
      20, the US), while the other flavor (CS-) was never paired with Tween20. Finally,
      in the post-acquisition phase, the two flavors were presented again without
      Tween20 and participants were asked to evaluate both of them for a last time. The
      control group as well as the lesion group rated the CS+ in the post-acquisition
      phase less favorable than in the pre-acquisition phase, while the ratings of the
      CS- remained the same in both phases. We clearly demonstrated evaluative
      conditioning in both test groups. Because the lesion group had still one intact
      ANC it would be premature, however, to conclude that the ANC is not involved in
      evaluative conditioning. We conclude that despite evidence for impaired fear
      conditioning, unilateral damage to the ANC does not impair evaluative
      conditioning.

PMID- 16085129
TI  - Social inhibition of seasonal fattening in wild and captive gray mouse lemurs.
AB  - Due to their differential reproductive investment, males and females often
      exhibit high differences in energy management. The main hypothesis tested in this
      study is that short photoperiod-induced fattening in the small primate Microcebus
      murinus is strongly affected by social cues. Short photoperiod-induced changes in
      body mass, lean mass and thyroid hormone T4 plasma levels measurements were
      investigated in wild and captive animals. Individual housing showed that both
      males and females are able to fatten. Fattening was associated with a slight
      increase of lean mass that reached a plateau after 3 weeks. In contrast, social
      grouping led to an inhibition of fattening, even when direct interactions were
      prevented. This social inhibition was mainly observed in males, especially when
      housed with females, suggesting that their low weight gain in the wild is due to
      female dominance. Accordingly, wild and captive animals of both sexes exhibited a
      decrease in T4 plasma levels, revealing a decrease in energy expenditure.
      Moreover, testis recrudescence observed after 20 weeks of short photoperiod
      exposure did not lead to any inhibition of fattening, indicating that males take
      advantage of female hibernation late in the dry season to fatten and use their
      fat reserves for the mating competition. Therefore, seasonal fattening may be
      used by females to prepare for hibernation and by males to prepare for the mating
      competition.

PMID- 16085130
TI  - Effect of breakfast composition on cognitive processes in elementary school
      children.
AB  - The relationship between breakfast composition and cognitive performance was
      examined in elementary school children. Two experiments compared the effects of
      two common U.S. breakfast foods and no breakfast on children's cognition. Using a
      within-participant design, once a week for 3 weeks, children consumed one of two
      breakfasts or no breakfast and then completed a battery of cognitive tests. The
      two breakfasts were instant oatmeal and ready-to-eat cereal, which were similar
      in energy, but differed in macronutrient composition, processing characteristics,
      effects on digestion and metabolism, and glycemic score. Results with 9 to 11
      year-olds replicated previous findings showing that breakfast intake enhances
      cognitive performance, particularly on tasks requiring processing of a complex
      visual display. The results extend previous findings by showing differential
      effects of breakfast type. Boys and girls showed enhanced spatial memory and
      girls showed improved short-term memory after consuming oatmeal. Results with 6
      to 8 year-olds also showed effects of breakfast type. Younger children had better
      spatial memory and better auditory attention and girls exhibited better short
      term memory after consuming oatmeal. Due to compositional differences in protein
      and fiber content, glycemic scores, and rate of digestion, oatmeal may provide a
      slower and more sustained energy source and consequently result in cognitive
      enhancement compared to low-fiber high glycemic ready-to-eat cereal. These
      results have important practical implications, suggesting the importance of what
      children consume for breakfast before school.

PMID- 16085131
TI  - Characterization of polymorphic solid-state changes using variable temperature X
      ray powder diffraction.
AB  - The aim of this study was to use variable temperature X-ray powder diffraction
      (VT-XRPD) to understand the solid-state changes in the pharmaceutical materials
      during heating. The model compounds studied were sulfathiazole, theophylline and
      nitrofurantoin. This study showed that the polymorph form of sulfathiazole
      SUTHAZ01 was very stable and SUTHAZ02 changed as a function of temperature to
      SUTHAZ01. Theophylline monohydrate changed via its metastable form to its
      anhydrous form during heating and nitrofurantoin monohydrate changed via
      amorphous form to its anhydrous form during heating. The crystallinity of
      SUTHAZ01, SUTHAZ02 and theophylline monohydrate were very high and stable.
      Nitrofurantoin monohydrate was also very crystalline at room temperature but
      during heating at lower temperatures the crystallinity decreased and started to
      increase strongly at the temperature where the sample had changed to the
      anhydrous form. The average crystallite size of sulfathiazole samples varied only
      a little during heating. The average crystallite size of both theophylline and
      nitrofurantoin monohydrate decreased during heating. However, the average
      crystallite size of nitrofurantoin monohydrate returned back to starting size at
      higher temperatures. These analyses showed that VT-XRPD can be used to
      effectively characterize polymorphic changes during heating.

PMID- 16085132
TI  - Direct high-performance liquid chromatographic analysis of D-tocopheryl acid
      succinate and derivatives.
AB  - A method of analysis of a Vitamin E derivative D-tocopheryl acid succinate (TS)
      in biological fluids and commercially available products is necessary to study
      the kinetics of in vitro and in vivo metabolism, tissue distribution, and content
      uniformity. A simple and inexpensive high-performance liquid chromatographic
      method was developed for the direct determination of D-tocopheryl acid succinate
      in commercially available products, rat serum, and rat tissues. This method can
      also be applied to the determination of 15 Vitamin E derivatives. Rat serum (0.1
      ml) was extracted with sodium dodecyl sulfate, ethanol, hexane, and then dried
      under nitrogen gas after addition of the internal standard, DL-alpha-tocopherol
      acetate. Separation was achieved on a C18 column with UV detection at 205 nm. The
      calibration curve for D-tocopheryl acid succinate was linear ranging from 0.025
      to 100 microg/ml. The mean extraction efficiency was >92%. Precision of the assay
      was <5% (CV), and was within 5% at the limit of quantitation (0.025 microg/ml).
      Bias of the assay was lower than 5%, and was within 5% at the limit of
      quantitation. The assay was applied successfully to the serum and tissue
      distribution of D-tocopheryl acid succinate in rats, various Vitamin E
      derivatives, and content uniformity in commercially available products containing
      D-tocopheryl acid succinate.

PMID- 16085133
TI  - Characterization of impurities in semi-synthetic vinorelbine bitartrate by HPLC
      MS with mass spectrometric shift technique.
AB  - A simple and sensitive method of high-performance liquid chromatography coupled
      with electrospray ionization mass spectrometry (HPLC/ESI-MS) was developed to
      separate and identify impurities in semi-synthetic vinorelbine bitartrate sample.
      The analytical HPLC was carried out on a reversed-phase C8 column using 0.02 M
      ammonium formicate buffer (pH 4.2) and methanol (46:54, v/v) as mobile phase at a
      flow rate of 0.8 ml/min at room temperature and a UV detection at 267 nm. The on
      line HPLC/ESI-MS/MS was performed using ion trap analyzer in positive ion mode.
      Applying mass spectrometric shift technique to HPLC/ESI-MS/MS analysis, four
      impurities were identified as 18'-O-demethylvinorelbine (impurity-1), 6'-N
      methylvinorelbine (impurity-2), 23-O-demethylvinoreline (impurity-3) and 17
      bromovinorelbine (impurity-4), respectively, in investigated vinorelbine
      bitartrate sample. The four impurities, in which the impurity-1 was not reported
      as the semi-synthetic process impurity for vinorelbine bitartrate elsewhere, were
      isolated by preparative high-performance liquid chromatography. Their structures
      were further confirmed by means of 1D and 2D NMR spectra. Structural elucidation
      by spectral data was discussed.

PMID- 16085134
TI  - Differentiation of Swertia Mussotii Franch from Artemisiae Capillaris Herba by
      capillary electrophoresis with electrochemical detection.
AB  - A high-performance capillary electrophoresis (CE) with electrochemical detection
      (ED) method is developed for differentiation of Swertia Mussotii Franch from
      Artemisiae Capillaris Herba in this work. Swertia Mussotii Franch contains a
      great deal of swertiamarin and mangiferin that are not present in Artemisiae
      Capillaris Herba, whereas Artemisiae Capillaris Herba consists of abundant
      chlorogentic acid. Therefore, determining their swertiamarin, mangiferin and
      chlorogentic acid contents can differentiate these two crude herbs. Operated in a
      wall-jet configuration, a 300 microm diameter carbon-disk electrode was used as
      the working electrode, which exhibits good response at +1000 mV (versus SCE) for
      the three analytes. With a separation voltage of 14 kV, the three analytes were
      separated within 14 min in a 52 cm length capillary in 50 mmol/l borax buffer (pH
      9.2). The system was demonstrated good stability and reproducibility with an
      R.S.D. of less than 5% for both migration time and peak current. This method was
      successfully used to analyze and identify the crude herbs with satisfactory assay
      results.

PMID- 16085135
TI  - A validated spectrofluorimetric method for determination of some psychoactive
      drugs.
AB  - Five psychoactive drugs namely, chlorpromazine HCl, thioridazine HCl,
      clomipramine HCl, imipramine HCl and desipramine HCl were analyzed by a simple
      spectrofluorimetric method. The method is based on oxidation of the studied drugs
      using cerium(IV) in presence of sulphuric acid and monitoring the fluorescence of
      the formed cerium(III) at lambda(ex.) = 254 nm and lambda(em.) = 355 nm. All
      variables affecting the reaction conditions such as; cerium(IV) concentration,
      sulphuric acid concentration, heating time, temperature and dilution solvents
      were carefully studied. The effect of potential interference due to common
      ingredients as glucose, sucrose, lactose, citric acid and propylene glycol were
      investigated. A validation study of the proposed method was carried out according
      to USP 2002. Beer's law was obeyed for all the studied drugs in the concentration
      range of 0.05-1.3 microg/ml. Limits of detection range was 0.035-0.038 microg/ml
      and limits of quantitation of 0.116-0.125 microg/ml were obtained. The method was
      successfully applied for the assay of the studied drugs in pure form and in
      pharmaceutical dosage forms. Results were compared with official methods. The t-
      and F-values were calculated and compared with the theoretical values, which
      indicate high accuracy and good precision of the proposed method.

PMID- 16085136
TI  - Stereospecific high-performance liquid chromatographic analysis of naringenin in
      urine.
AB  - A method of analysis of naringenin [(+/-)-4',5,7-trihydroxyflavanone] in
      biological fluids is necessary to study the kinetics of in vitro and in vivo
      metabolism, tissue distribution in fruits and humans. A simple high-performance
      liquid chromatographic method was developed for simultaneous determination of
      naringenin enantiomers in rat and human urine. Urine (0.1 ml) was precipitated
      with cold acetonitrile after addition of the internal standard, daidzein.
      Separation was achieved on a Chiralcel OD-RH column with UV detection at 292 nm.
      The calibration curves were linear ranging from 0.5 to 100 microg/ml for each
      enantiomer. The mean extraction efficiency was >99%. Precision of the assay was
      <9.4% (CV), and was within 5.4% at the limit of quantitation (0.5 microg/ml).
      Bias of the assay was lower than 16%, and was within 15% at the limit of
      quantitation. The assay was applied successfully to the urinary excretion of
      naringenin in rats and humans.

PMID- 16085137
TI  - Sensitive HPLC method for quantitation of paclitaxel (Genexol in biological
      samples with application to preclinical pharmacokinetics and biodistribution.
AB  - A sensitive, specific and reproducible HPLC method has been developed and
      validated for the quantitative determination of paclitaxel in plasma, tissues and
      tumor of mice. Tissue specimens including liver, kidneys, spleen, lungs, heart
      and tumor were separately homogenized in bovine serum albumin (BSA, 40 g/l) in
      water. Plasma or tissue homogenates (0.1 ml) containing paclitaxel and internal
      standard (dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxy biphenyl-2',2'
      dicarboxylate (DDB), I.S.) were extracted by ethyl acetate (10 ml). A 4.6 mm x
      250 mm ODS column was used to separate the components in biological samples with
      UV detection at 227 nm and gradient system was applied to a quantitation of
      paclitaxel consisting of acetonitrile-deionized water. The I.S. and paclitaxel
      were eluted at 13.7 and 18.0 min, respectively, and no interfering peaks were
      observed. Linear relationships (r(2) > 0.999) were obtained between the peak
      height ratios and the corresponding biological sample concentrations over the
      range of 0.1-20 microg/ml. The average intra- and inter-day variations (% R.S.D.s
      and % deviations) of the assay for biological samples were less than 10%. The LOD
      and LOQ were 5 and 10 ng/ml, respectively, for paclitaxel using a microsample
      volume (100 microl) of plasma sample. This HPLC method has been successfully
      applied for the determination of paclitaxel in pharmacokinetic and
      biodistribution study in after administration of 50 mg equivalent paclitaxel/kg
      dose of paclitaxel-loaded polymeric micelle and 20 mg equivalent paclitaxel/kg
      dose of Taxol to female SPF C57BL/6 mice.

PMID- 16085138
TI  - Voltammetric study of interaction between polymers (PEI and TMO) and pDNA on a
      hanging mercury drop electrode.
AB  - Electrochemical DNA biosensors can become a powerful tool for the investigation
      of potent changes on the plasmid DNA structure caused by polymers used as non
      viral vectors in gene delivery. Trimethylated chitosan oligomer (TMO) and
      polyethylenimine (PEI), offering biocompatibility, low immunogenicity and minimal
      cytotoxicity, are being studied as model non-viral carriers. The information
      obtained is intended to serve as a basis for developing a new analytical system
      for the study of the effect of any physically or chemically synthesized polymer
      on DNA structure.

PMID- 16085139
TI  - Decreased mucin concentrations in tear fluids of contact lens wearers.
AB  - Characteristics of tear-film may be influenced by contact lens wear, because
      contact lenses present the habitual, direct rubbing action of the lids upon the
      covered ocular surface and may cause changes of tear-film. In the present paper,
      influence of contact lens on proteins in tear samples was studied using
      carbohydrates attached to the protein as a marker. We found that N
      acetylneuraminic acid (Neu5Ac) was significantly decreased in tear samples of
      volunteers wearing contact lens (wearing, 86.1 +/- 57.7 nmol/ml; normal, 190.2 +/
      121.9 nmol/ml). Analysis by polyacrylamide gel electrophoresis demonstrated that
      the amounts of major proteins in tear fluids, such as lactoferrin and secretory
      immunoglobulin A were not changed upon wearing contact lenses. In contrast,
      cellulose acetate membrane electrophoresis revealed that mucin band in tear
      samples from contact lens wearers showed significant decrease as examined by
      lectin staining.

PMID- 16085140
TI  - Mechanism of interaction of the non-steroidal antiinflammatory drugs meloxicam
      and nimesulide with serum albumin.
AB  - The mechanism of interaction of the non-steroidal antiinflammatory drugs
      meloxicam and nimesulide with human and bovine serum albumin has been studied
      using fluorescence spectroscopy. There was only one high affinity site on serum
      albumin for both the drugs with association constants of the order of 10(5).
      Negative enthalpy (DeltaH(0)) and positive entropy (DeltaS(0)) values in the case
      of both meloxicam and nimesulide showed that both hydrogen bonding and
      hydrophobic interactions play a role in the binding of these drugs. Binding
      studies in the presence of the hydrophobic probe 1-anilinonaphthalene-8-sulfonate
      (ANS) showed that the binding of meloxicam and nimesulide to serum albumin
      involves predominantly hydrophobic interactions. Stern-Volmer analysis of the
      quenching data showed that quenching is highly efficient and that the tryptophan
      residues in hydrophobic regions of the proteins are fully exposed to the drugs.
      Thus these drugs are bound to albumin by hydrophobic interactions as well as
      hydrogen bonding at a site, which is close to the tryptophan residues. An
      increase of the pH and ionic strength caused an increase in the concentration of
      free drug, although the effect was not very significant.

PMID- 16085141
TI  - Some properties of the interaction between 2,2'-diselenadibenzoic acid and serum
      albumins.
AB  - The binding of 2,2'-diselenadibenzoic acid to bovine serum albumin (BSA) and
      human serum albumin (HSA) was studied by using fluorescence spectroscopy. The
      measurement was performed in Tris-HCl buffer aqueous medium at pH = 7.40. The
      quenching constant at 303 K was (3.277 +/- 0.046) x 10(13) L mol(-1) s(-1) for
      BSA, and (3.946 +/- 0.002) x 10(12) L mol(-1) s(-1) for HSA. Decreased quenching
      was observed in association with increased temperature. Our findings show that
      the observed binding constant is dependent on the ionic strength of the medium.
      It is said that electrostatic interactions play a role in the binding of 2,2'
      diselenadibenzoic acid to serum albumin, in addition to the hydrophobic
      association. The decrease of the linearity of S-V plot demonstrates reduced
      binding of ligand to the protein in the presence of anionic surfactants such as
      sodium dodecyl sulfate (SDS), which indicates that 2,2'-diselenadibenzoic acid
      most likely binds to the hydrophobic pockets within sub-domain IIA of serum
      albumin, the same site as SDS.

PMID- 16085142
TI  - A fast and sensitive liquid chromatographic-tandem mass spectrometric method for
      assay of lorazepam and application to pharmacokinetic analysis.
AB  - A fast and sensitive method of coupled high-performance liquid chromatography
      electrospray tandem mass spectrometry for the assay of lorazepam in human plasma
      was developed. Plasma samples were simply treated with acetonitrile to
      precipitate and remove proteins and the isolated supernatants were directly
      injected into the HPLC/MS/MS system. Chromatographic separation was performed on
      a Zorbax C(18) (100 x 2.1 mm I.D.) column with a 65:35 (v/v) mixed solution of
      acetonitrile and 10mM aqueous formic acid being used as mobile phase. With
      diazepam as an internal standard, quantification was performed by selected
      reaction ion monitoring of the transitions of m/z 321--> m/z 275 for lorazepam
      and m/z 285--> m/z 193 for the internal standard. The assay was validated in the
      concentration range of 0.71-71.3 ng/ml in human plasma. A detection limit of 0.10
      ng/ml for lorazepam was achieved, and inter- and intra-run precisions of better
      than 4.4% (R.S.D.) were observed. The developed method has been successfully
      applied for pharmacokinetic study of the drug in man.

PMID- 16085143
TI  - Determination of the relative amounts of three crystal forms of a benzimidazole
      drug in complex finished formulations by FT-Raman spectroscopy.
AB  - A 5% (m/m) premix for animal use was quantitatively characterized for the
      polymorph composition of its benzimidazole drug substance. Raman spectra of
      reference samples (pure polymorphs A, B and C in lactose at a concentration of
      5%, m/m) were compared with the spectra of benzimidazole samples with a known
      polymorph composition and with the spectra of uncharacterized premixes. The raw
      intensities of 78 selected wavenumbers were vector-normalized and application of
      stepwise linear regression models estimated the relative quantities of the
      benzimidazole-drug polymorphs A, B and C in the different samples. Modelling
      results of the samples with known polymorph composition were in compliance with
      the expected concentrations, validating the proposed methodology. The
      benzimidazole drug substance in the premixes was predominantly polymorph B.
      Although statistically not significant, some traces of polymorph A could not be
      ruled out. Similar analyses were performed to evaluate the solid-state stability
      of the benzimidazole drug substance in another drug formulation, i.e. a
      suspension-emulsion. Suspension-emulsions originally determined as containing
      polymorph B benzimidazole drug substance were stored for 12 months at 25 degrees
      C/60%RH. FT-Raman spectroscopy revealed that no polymorph transformations
      occurred during this storage.

PMID- 16085144
TI  - Separation and determination of pseudoephedrine, dextromethorphan,
      diphenhydramine and chlorpheniramine in cold medicines by nonaqueous capillary
      electrophoresis.
AB  - An easy, rapid and simple nonaqueous capillary electrophoresis (NACE) method was
      developed for the identification and determination of four basic nitrogenous
      compounds, i.e. pseudoephedrine (PE), dextromethorphan (DXM), diphenhydramine
      (DHM) and chlorpheniramine (CLP). The most suitable running buffer was composed
      of 40 mM ammonium acetate, 10% acetonitrile (ACN) in methanol with a fused-silica
      capillary column (47 cm x 75 microm i.d.), 25 kV applied voltage and 25 degrees C
      capillary temperature. The calibration curves revealed linear relationships
      between the peak area for each analyte and its concentration (correlation
      coefficients: 0.9993 for PE, 0.9971 for DXM, 0.9991 for DHM, and 0.9995 for CLP,
      respectively). The relative standard deviations of the migration time and peak
      area of the four compounds were 0.37, 3.90, 0.73 and 0.68, and 2.80, 3.50, 1.60
      and 3.70%, respectively. The method was successfully applied to determine the
      four compounds in five cold medicines, the recoveries of the four constituents
      ranging between 91 and 109%.

PMID- 16085145
TI  - Electroanalytical study of the antidepressant sertraline.
AB  - A flow injection square wave cathodic stripping voltammetric method has been
      developed for the determination of sertraline in a pharmaceutical preparation.
      The method shows linearity between peak current intensity and sertraline
      concentration for the interval between 0.20 x 10(-6) and 1.20 x 10(-6) mol L(-1).
      Limits of detection and quantification were found to be 1.5 x 10(-7) and 5.0 x 10
      (-7) mol L(-1), respectively. Up to 70 samples per hour can be analysed with a
      good precision (R.S.D. = 2.5%). The proposed method was successfully applied to
      the determination of sertraline in a commercial product. In the voltammetric
      determination of sertraline in flow, a high sample rate is obtained at reduced
      costs, opening the possibility to compete with the chromatographic methods
      generally used for this analysis.

PMID- 16085146
TI  - A new method for the analysis of amikacin using 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate (AQC) derivatization and high-performance liquid
      chromatography with UV-detection.
AB  - A simple and sensitive reversed-phase liquid chromatographic method has been
      developed for the determination of amikacin (AMK) by derivatization. The method
      is based on the pre-column derivatization of AMK with 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate (AQC). The derivatization reaction proceeds in
      aqueous solution at room temperature with a borate buffer of pH 8.0. The
      formation of the corresponding derivative of AMK is instantaneous and it is
      stable for more than 36 h. Detection was performed by UV-absorption instead of
      fluorescence. Several factors influencing the derivatization reaction yields were
      studied and optimized. The system offered the following analytical parameters:
      limit of detection (LOD) of 0.068 micro g ml(-1) (3sigma), linear correlation
      coefficient of 0.9998 and linear range response from 2 to 50 microg ml(-1). The
      precision of the method was <1%. As a preliminary application, the method has
      been successfully applied to the amikacin determination in parenteral
      pharmaceutical formulations.

PMID- 16085147
TI  - Determination of thalidomide by high performance liquid chromatography: plasma
      pharmacokinetic studies in the rat.
AB  - A sensitive and simple high performance liquid chromatography (HPLC) method was
      developed and validated for the determination of thalidomide in rat plasma.
      Chromatography was accomplished with a reversed-phase Hypersil C18 column. Mobile
      phase consisted of acetonitrile-10 mM ammonium acetate buffer (pH 5.50) (28:72,
      v/v), at a flow rate of 0.8 ml/min. Thalidomide was monitored by ultraviolet
      detector at 220 nm and it gave a linear response as a function of concentration
      over 0.02-50 microM. The limit of quantitation in rat plasma was 0.50 ng (0.02
      microM plasma concentration) with an aliquot of 20 microl. Results from a 3-day
      validation study indicated that this method allows for simple and rapid
      quantitation of thalidomide with excellent accuracy and reliability. Using this
      validated assay, the effect of coadministered irinotecan (CPT-11) on the plasma
      pharmacokinetics of thalidomide in rats was determined. Coadministration of CPT
      11 (intravenously, 60 mg/kg) increased the maximum plasma concentration (C(max))
      and area under the plasma concentration-time curve (AUC(0-10h)) of thalidomide by
      32.29 and 11.66%, respectively, as compared to the control, but none of the
      effect of CPT-11 was of statistical significance (P > 0.05). Concomitant CPT-11
      also caused a 10.04% decrease in plasma clearance (CL) and 14.51% decrease in
      volume of distribution (V(d)) (P > 0.05). These results suggest that
      coadministered CPT-11 did not significantly alter the plasma pharmacokinetics of
      thalidomide in rats. Further studies are warranted to explore the pharmacokinetic
      and pharmacodynamic interactions between CPT-11 and thalidomide.

PMID- 16085148
TI  - Fluorometric assay of tiopronin based on inhibition of multienzyme redox system.
AB  - In this paper, a simple and sensitive fluorimetric method for the determination
      of tiopronin (N-(2-mercaptopropionyl)-glycine) is proposed. The method is based
      on the strong inhibitory effect of tiopronin on the multienzyme redox system of
      hemoglobin, nicotinamide adenine dinucleotide (NADH) and H(2)O(2), in which the
      intrinsic fluorescence of NADH was employed as the detection signal. The
      calibration graph is linear in the range 6.13 x 10(-7) to 6.13 x 10(-6) M with a
      detection limit of 1.65 x 10(-7) M and the relative standard deviation of 2.02%.
      Kinetics in the pseudo-first-order conditions was investigated by stopped-flow
      spectrofluorometry and the inhibition mechanism of tiopronin was verified of the
      competitive type.

PMID- 16085149
TI  - Shelf lives of aseptically prepared medicines--stability of
      piperacillin/tazobactam in PVC and non-PVC bags.
AB  - Parenteral aseptic preparations of piperacillin/tazobactam are used frequently in
      hospitals, but there is limited published information on their stability in
      polyvinyl chloride (PVC) and polyolefine laminate (non-PVC). The purpose of this
      study was to evaluate the stability in these containers and to determine the
      optimum validated shelf life so that the formulations may be prepared in bulk in
      appropriately licensed facilities. In the first study, the stability of
      piperacillin/tazobactam 45 mg/ml was determined in polyvinyl chloride and
      polyolefine laminate bags in 0.9% (w/v) sodium chloride at 7 degrees C, 25
      degrees C/60% relative humidity (RH) and room temperature in the light (RTL) with
      storage up to 41 days for PVC bags and 98 days for non-PVC bags. In the second
      study, the stability of piperacillin/tazobactam 45 mg/ml was determined in non
      PVC bags in a buffered sodium chloride formulation at 7 degrees C, 25 degrees
      C/60% RH and RTL with storage up to 201 days. Samples from each admixture were
      analysed for piperacillin concentration, tazobactam concentration and appearance
      of decomposition products by stability indicating high-performance liquid
      chromatography (HPLC). The pH and appearance of solution and container were also
      monitored. Shelf lives were calculated using the maximum rate method. Tazocin was
      found to be stable in 0.9% (w/v) sodium chloride in PVC bags for up to 5 days at
      7 degrees C and 4 days at both 25 degrees C and RTL. In non-PVC bags, it was
      stable for 17, 4 and 3 days, respectively. It was stable in the buffered sodium
      chloride formulation in non-PVC bags for up to 58 days at 7 degrees C, 10 days at
      25 degrees C and 7 days at RTL.

PMID- 16085150
TI  - Lower levels of occupation, income and education are strongly associated with a
      longer smoking duration: multivariate results from the 2001 Australian National
      Drug Strategy Survey.
AB  - OBJECTIVE: Our aim was to investigate the association of socio-economic status
      (SES) with duration of smoking among ever smokers. STUDY DESIGN: We used a
      subsample of ever smokers (n = 9973) aged 18+ years from the 2001 National Drug
      Strategy Household Survey (conducted by the Australian Institute of Health and
      Welfare), which involved a multistage area sample and mainly self-administered
      questionnaires. METHODS: The outcome was smoking duration from onset to
      cessation. We used survival analysis to predict smoking duration. RESULTS:
      Results showed that smoking duration from onset to cessation was 14% longer for
      blue-collar workers than for professionals. Respondents who earned under 300 US
      dollars/week smoked for 38% longer than those earning 800 US dollars+/week.
      Individuals with less than 10 years of education smoked for 13% longer than those
      with 12+ years of education. CONCLUSIONS: Smokers from lower social strata smoke
      for much longer durations. This finding and the fact that smoking increases the
      likelihood of financial stress suggest that lower SES smokers who experience
      financial stress are more likely to suffer a longer period of compromised living
      standards than their counterparts in the higher strata. The financial and health
      burdens of smoking coupled with social inequalities in smoking behaviour suggest
      that smoking may exacerbate social class differences in health and standards of
      living. Thus, targeting smoking among disadvantaged groups would not only
      represent a public health policy but also a social policy to reduce social
      inequalities.

PMID- 16085151
TI  - Intimate partner violence: forms, consequences and preparedness to act as
      perceived by healthcare staff and district and community leaders in a rural
      district in northern Vietnam.
AB  - OBJECTIVES: A qualitative study was conducted among healthcare staff and district
      and community leaders in May and June 2002 to describe their perceptions of
      violence occurring between intimate partners. It focused on male violence towards
      females, and its forms, consequences and preparedness to act in a rural setting
      in Vietnam. METHODS: Twenty men and 20 women were strategically selected for
      focus group discussions and a phenomenographic approach was employed. FINDINGS:
      Violence was described not only as physical but also, primarily, as affecting
      women's mental health status. Mental violence was exemplified as verbally
      offending, ignoring or humiliating a woman. Sexual abuse was mentioned less
      frequently. IPV was considered to be a private matter, occurring in the home away
      from relatives, neighbours and the local community. Only very serious cases would
      seek health care. Divorce and deteriorating family finances were reported as
      serious consequences, not least for the children. Local reconciliation groups,
      comprised of trusted community members, played a role in mediating, while health
      professionals were found to be uninformed about prevalence rates and reluctant to
      intervene. CONCLUSIONS: Gender-based violence needs to receive attention from
      policy makers, and effective advocacy programmes are needed at all levels. In
      Vietnam, partner violence against women seems to be recognized at Government
      level. At community level, Women's Union staff and local reconciliation groups
      are prepared to act. However, the subject is surrounded by silence. We found that
      healthcare workers exhibited a lack of understanding of violence against women as
      a health problem in their own working environment.

PMID- 16085152
TI  - Factors affecting the uptake of cardiac rehabilitation services in a rural
      locality.
AB  - INTRODUCTION: A number of studies have investigated factors affecting uptake of
      cardiac rehabilitation services. However, little information on factors affecting
      uptake of services in rural localities is available. STUDY DESIGN: A cross
      sectional survey. METHODS: A survey of patients eligible for cardiac
      rehabilitation was undertaken to investigate uptake of services. The effects of
      individual and geographic factors on service utilization were explored. RESULTS:
      Utilization rates for cardiac rehabilitation services within the South
      Staffordshire locality are low, with 59.3% of eligible patients invited to attend
      cardiac rehabilitation services following discharge from hospital, 38.6%
      attending and 22.5% completing the programme. Two factors were independently
      associated with low service utilization. Patients under the age of 65 years are
      1.90 [95% confidence intervals (CI) 1.01-3.65] times more likely to complete
      rehabilitation than patients aged over 65 years, and women are only 0.48 (95% CI
      0.22-1.03) times as likely as men to complete rehabilitation. The major reported
      barrier to utilization of services was access. This included problems with public
      transport, parking and the time and location of classes. Access and medical
      problems were significantly higher in older people and may have contributed to
      their low overall completion rate. Electoral ward deprivation, geographical
      access score, living in an urban or rural electoral ward, electoral ward of
      residence and provider were not significantly associated with service
      utilization. CONCLUSIONS: Overall, utilization rates were low. No geographical
      factors were associated with uptake of services, although the possible effect may
      have been mediated by the relative affluence of the locality. Two individual
      factors, age and sex, were most likely to influence uptake.

PMID- 16085153
TI  - Involvement of opioidergic and alpha2-adrenergic mechanisms in the central
      analgesic effects of non-steroidal anti-inflammatory drugs in sheep.
AB  - The level within the central nervous system where non-steroidal anti-inflammatory
      drugs (NSAIDs) produce analgesia and the mechanisms by which they mediate this
      effect are still uncertain. This study assessed the central analgesic effects of
      ketoprofen, phenylbutazone, salicylic acid and tolfenamic acid in sheep implanted
      with indwelling intrathecal (i.t.) catheters and submitted to mechanical noxious
      stimulation. The sheep received i.t. cumulative concentrations (0.375-200 microM;
      100 microL) as well as a single intravenous (i.v.) dose (3, 8, 10 and 2 mg/kg,
      respectively) of each NSAID. The sheep were also given i.t. naloxone (5.49 mM;
      100 microL) and atipamezole (4.03 mM; 100 microL) prior to i.v. ketoprofen. None
      of the i.t. NSAIDs increased mechanical thresholds. Intravenously, only
      ketoprofen and tolfenamic acid raised the pain thresholds. The hypoalgesic effect
      of i.v. ketoprofen was prevented by i.t. naloxone or atipamezole. Although NSAIDs
      had no direct effect on the spinal cord, their analgesic action appeared to be
      spinally mediated.

PMID- 16085154
TI  - Correlation between a proteolytic method and a radioimmunoassay for porcine serum
      pepsinogen concentrations.
AB  - The measurement of serum pepsinogen concentrations by enzymatic method and
      immunoassay provides diagnostic values and should be helpful in the detection of
      gastric diseases related to a rise of blood pepsinogen. In the present study, the
      correlation between a conventional enzymatic method and a recently developed
      radioimmunoassay (RIA) for serum pepsinogen A was investigated. A total of 123
      sera samples of porcine foetuses (n = 28), adult healthy pigs (n = 56), pigs with
      parakeratosis (n = 25) and pigs with ulceration of the pars oesophagea (n = 14)
      were tested. Overall, there was a slight correlation between the two methods (r =
      0.60). In relation to individual animal groups, the correlations (r) were 0.39
      (P>0.05), 0.74 (P<0.001), 0.19 (P>0.05) and 0.34 (P>0.05) in foetuses, healthy
      pigs, pigs with parakeratosis and pigs with ulcers, respectively. In both
      methods, pepsinogen concentrations (means+/-SE) were significantly higher
      (P<0.05) in pigs with parakeratosis (1778 +/- 86.00 mUTyr/L; 690 +/- 53.00 ng/mL)
      and in pigs with ulcers (2026 +/- 153.00 mUTyr/L; 1747 +/- 94.00 ng/mL) when
      compared to healthy pigs (935 +/- 58.00 mUTyr/L; 275 +/- 35.00 ng/mL). The
      proteolytic method gave a significant increased activity (P<0.05) in foetuses
      (1150 +/- 82.00 mUTyr/L) vs. (935 +/- 58.00 mUTyr/L) in healthy adult pigs,
      indicating an additional proteolytic activity in the sera of foetuses or
      neonates.

PMID- 16085157
TI  - Osteoporosis and measurement of bone mass in children and adolescents.
AB  - Osteoporosis increasingly is recognized as a pediatric concern. Fragility
      fractures occur in children and adolescents with genetic disorders and those with
      a variety of chronic diseases. Others may not fracture in childhood but reach
      adulthood with a reduced peak bone mass and increased lifelong risk of
      osteoporosis. This article reviews the indications for pediatric bone density
      testing, the strengths and limitations of densitometry methods, and the
      challenges of interpreting the results. The goals are to demystify the
      densitometry report and to clarify the role of bone density tests in assessing
      and managing skeletal health in children.

PMID- 16085158
TI  - Rickets and vitamin D deficiency in children and adolescents.
AB  - This article discusses the pathogenesis, epidemiology, prevention, and treatment
      of nutritional rickets in children, highlighting the roles of exclusive
      breastfeeding and low dietary calcium intakes in its pathogenesis. The worldwide
      nature of the problem is described. Preventive strategies are discussed, and
      various treatment options are provided.

PMID- 16085159
TI  - Inhaled steroids for children: effects on growth, bone, and adrenal function.
AB  - Inhaled corticosteroids are the first-line therapy for persistent asthma in
      children. Major safety concerns of long-term inhaled corticosteroid therapy
      include suppression of adrenal function and impaired growth and bone development.
      Proper interpretation of inhaled corticosteroid safety requires knowledge of
      differences among various drug devices. Dosage, type of inhaler device used,
      patient technique, and characteristics of the individual drug influence systemic
      effects of inhaled corticosteroids. Systemic side effects can occur when
      continuous high-dose treatment is required for severe asthma or when prescribed
      dosage is excessive and compliance is unusually good. Recent studies confirm that
      benefits of inhaled corticosteroids outweigh potential adverse effects and the
      risks associated with poorly controlled asthma.

PMID- 16085160
TI  - Idiopathic short stature.
AB  - The diagnostic term, idiopathic short stature, has emerged over the past 30 years
      and refers to children with short stature of unknown etiology. Controversy exists
      regarding the scope of the diagnosis and options for its treatment. This article
      reviews origins of the diagnosis idiopathic short stature and current diagnostic
      criteria, scientific advances in delineating etiologies of idiopathic short
      stature, management options, and implications of management decisions for child
      health.

PMID- 16085161
TI  - Diagnostic and therapeutic advances in growth hormone insensitivity.
AB  - Diagnostic and therapeutic advances in growth hormone insensitivity (GHI) have
      occurred principally in two areas: the molecular characterization of patients
      with GHI and treatment with recombinant human insulin like growth factor-I (IGF
      I). This article discusses the current status of molecular diagnosis across the
      spectrum of the disorder. Treatment with recombinant human IGF-I in classical
      cases is summarized, and potential new targets for treatment are discussed
      together with the potential for therapy using the newly developed compound
      recombinant human IGF-I/IGF binding protein-3.

PMID- 16085162
TI  - Endocrine and metabolic consequences of intrauterine growth retardation.
AB  - Size at birth and early infancy growth rates have been linked to long-term risks
      for diseases, such as type 2 diabetes and cardiovascular disease. These
      associations could be explained by permanent programming of metabolic responses
      and selective survival of those genetically predisposed to such adaptations.
      These epidemiologic associations may also affect long-term disease risk in short
      small-for-gestational age children, who are often treated with growth hormone.
      Study of the mechanisms and genetic factors involved in the association between
      small size at birth, rapid postnatal weight gain, and adult disease may promote
      the early identification of subjects with the highest disease risk and new
      opportunities to develop targeted early interventions.

PMID- 16085163
TI  - Regulation and disorders of pubertal timing.
AB  - Disorders of pubertal timing are common and challenging problems for pediatric
      endocrinologists. Early or late puberty can have immediate effects on a child's
      psychosocial well-being and may have long-term effects on adult stature. Much is
      known about the regulation of the hypothalamic-pituitary-gonadal axis, but the
      triggers of pubertal onset in the general population remain elusive. This article
      reviews recent data suggesting a possible shift in the age of pubertal onset;
      current knowledge regarding factors that regulate the onset of puberty; and the
      etiologies, diagnosis, and treatment of precocious and delayed puberty.

PMID- 16085164
TI  - Hormonal and metabolic consequences of childhood obesity.
AB  - It is apparent that chronic illnesses such as type 2 diabetes and cardiovascular
      disease originate in childhood. Obesity in childhood and adolescence hastens
      their development, enhances their rates of progression, increases the risks of
      severe complications, and if persistent, reduces life expectancy.

PMID- 16085165
TI  - Type 2 diabetes in children and youth.
AB  - The number of children and youth diagnosed with type 2 diabetes has increased
      dramatically over the last decade. Much still needs to be learned about why this
      epidemic is occurring presently with regard to other environmental factors that
      might promote insulin resistance and beta-cell failure. The TODAY trial will help
      to determine the best treatment strategies to improve glycemia, reduce
      complications, and ameliorate insulin resistance and beta-cell failure. As type 2
      diabetes emerges as a worldwide public health problem, improved care for affected
      youth must be coupled with a focus on prevention.

PMID- 16085167
TI  - Oral contraceptives and the management of hyperandrogenism-polycystic ovary
      syndrome in adolescents.
AB  - Appropriate management of polycystic ovary syndrome in adolescents depends on
      recognizing the syndrome, which can have a variety of presenting complaints and
      must be differentiated from other causes of hyperandrogenism, as well as not
      dismissed as "normal adolescence." Oral contraceptives have long been considered
      the first line of treatment by obstetrician/gynecologists and have many
      advantages in treating the aspects of PCOS that are most bothersome to teens.
      Because of the potential risk for cardiovascular disease, early diagnosis and
      management may be helpful in minimizing the risk of the early metabolic
      correlates of adult disease.

PMID- 16085166
TI  - Polycystic ovary syndrome in adolescence.
AB  - Polycystic ovary syndrome (PCOS) is a syndrome of variable combinations of
      menstrual irregularity, hirsutism or acne, and obesity. It can be diagnosed in
      adolescence and has early childhood antecedents. PCOS is the single most common
      endocrine cause of an ovulatory infertility and a major risk factor for the
      metabolic syndrome and, in turn, development of type 2 diabetes mellitus in
      women. Thus, it appears that PCOS increases a woman's risk of developing
      cardiovascular disease. Therefore, identifying girls at risk for PCOS and
      implementing treatment early in the development of PCOS may be an effective means
      of preventing some of the long-term complications associated with this syndrome.
      This article reviews the definition, clinical features, diagnosis, and treatment
      of PCOS.

PMID- 16085168
TI  - Thyroid nodules and cancers in children.
AB  - Thyroid nodules are clinically evident in approximately 1% of children and about
      30% of these are malignant. In addition to requiring appropriate surgery, thyroid
      hormone replacement in and follow-up monitoring of patients who are members of
      families with tumor syndromes must be studied for other components of these
      syndromes.

PMID- 16085169
TI  - Diagnostic imaging of the thyroid and adrenal glands in childhood.
AB  - This article reviews the clinical utility of modern imaging techniques,
      particularly ultrasound (US), CT, and MRI in children with disorders of the
      thyroid and adrenal glands. Radionuclide scanning is the modality of choice in
      making the anatomic diagnosis in neonates with congenital hypothyroidism, while
      US is most useful in defining nodular thyroid disease. CT and MRI of the thyroid
      tend to be limited to defining the extent of thyroid carcinoma. Adrenal US is an
      essential step in the differential diagnosis of ambiguous genitalia or salt
      losing crises in the newborn, while CT and MRI are more useful in defining the
      anatomy of the adrenals in older children with tumors or diffuse hyperplasia of
      the glands.

PMID- 16085170
TI  - Endocrine late effects of cancer treatment.
AB  - Endocrinopathies are significant consequences of the treatment of childhood
      cancers. The risk of developing these adverse events is related to the underlying
      disease and its treatment with cytotoxic agents and radiation therapy. This
      article reviews hypothalamic-pituitary, thyroid, and gonadal dysfunction, as well
      as osteopenia-osteoporosis and obesity.

PMID- 16085171
TI  - Intersexed states: diagnosis and management.
AB  - Traditional guidelines for the care of intersexed patients have been questioned
      by dissatisfied adult intersexed patients. The controversy surrounding this issue
      comes from a handful of highly publicized intersexed cases with poor outcomes,
      representing a minority of the intersexed population, which serve as an
      appropriate call to reassess this difficult issue. Re-evaluation of management
      strategies must acknowledge the complaints of those who oppose the traditional
      management paradigm and address scientific and surgical advancements and the
      roles they should play. This article reviews these issues, attempts to formulate
      a contemporary approach, and acknowledges the gaps that remain in our knowledge.

PMID- 16085172
TI  - Public-private partnerships: an overview.
AB  - The development and marketing of medicines needed specifically to combat diseases
      of the developing world are commercially unattractive because the populations
      concerned are among the poorest on earth. Partnerships which bring together
      pharmaceutical companies, academics, not-for-profit organizations,
      philanthropists, governmental and inter-governmental agencies are an increasingly
      popular solution. These partnerships result in a complementarity of skills and
      resources that can accelerate the development and delivery of new medicines to
      those in need. Over the last 10 years or so, these public-private partnerships
      (PPPs) have grown significantly in number and diversity. However, they tend to
      cluster into two main groups: those dealing with product development (PD PPPs),
      and those concerned with improving the access of new medicines to target
      populations (Access PPPs). The Initiative on Public-Private Partnerships for
      Health was set up four years ago to monitor the performance of these new
      partnerships. After a series of studies of Access PPPs, it concluded that they
      provide significant benefits with very few side effects, particularly in the case
      of tropical diseases.

PMID- 16085173
TI  - Low prevalence of Plasmodium falciparum infection among asymptomatic individuals
      in a highland area of Kenya.
AB  - In areas of highly seasonal Plasmodium falciparum transmission, the presence of a
      large reservoir of persistently infected but asymptomatic individuals in the dry
      season leads to predictable increases in the incidence of clinical malaria in the
      rainy season. Highland areas, by contrast, are prone to unpredictable epidemics
      of malaria. To determine the importance of persistent asymptomatic infection in
      highland areas, we assessed asymptomatic individuals in the highland area of
      Kipsamoite, Kenya for the presence of P. falciparum blood-stage infection by
      microscopy and PCR. Five sample collections were performed during rainy and dry
      seasons over a 31-month period. The final collection was obtained at the start of
      a rainy season epidemic. Asymptomatic parasitemia was infrequent, ranging from
      1.3 to 8.1% by microscopy and 5.9 to 14.5% by PCR testing. Microscopy had low
      sensitivity (22.2-54.8%) but excellent specificity (95.4-100%) in comparison to
      PCR testing. Frequency of asymptomatic parasitemia did not differ by age.
      Gametocyte prevalence was <1% in all periods, except at the start of the
      epidemic, when it increased to 5.3%. In this epidemic-prone highland area, inter
      epidemic periods are characterized by low frequencies of asymptomatically
      infected individuals. Increases in gametocyte prevalence may be an early
      indicator of impending outbreaks.

PMID- 16085174
TI  - TB: a partnership for the benefit of research and community.
AB  - A public-private partnership (PPP) involving Stellenbosch University in South
      Africa and GlaxoSmithKline (GSK) has benefited both research and a local
      community where tuberculosis (TB) is endemic. The venture, part of GSK's Action
      TB programme, enabled the University's Desmond Tutu TB Centre to establish an
      epidemiological field site in two suburbs of Cape Town where the annual risk of
      TB infection is 3.5%. Collaboration between the centre and GSK focused on the
      development of a surrogate marker model able to predict patient outcome with
      relative accuracy. Such models may be useful tools for diagnosis/prognosis and
      for shortening clinical trials of novel TB agents. Other research findings
      stemming from the Action TB partnership suggest that exogenous reinfection is
      responsible for the majority of relapse cases and that adults often have
      infection with multiple strains. The local community has been empowered by the
      implementation of the Directly Observed Treatment, Short-course (DOTS) programme
      and benefited from improved education about health in general and TB in
      particular. The centre has also provided employment for many local people in
      field work and other roles. Meanwhile, national and international publicity about
      the centre's work has aided in generating the essential political will to
      allocate resources and shape healthcare priorities, benefiting this impoverished
      community.

PMID- 16085175
TI  - Drug discovery and beyond: the role of public-private partnerships in improving
      access to new malaria medicines.
AB  - Traditional pharmaceutical research and development (R&D) strategy has failed to
      address the desperate need for new antimalarial drugs. The populations affected
      are too poor to attract commercially-driven R&D. Over the last few years, a new
      model, the public-private partnership for product development, has radically
      changed the antimalarial R&D landscape. The partnerships bring together academic
      and industry expertise with funding from governmental, philanthropic and
      charitable sources. The Medicines for Malaria Venture, a not-for-profit
      foundation based in Geneva, aims to develop new antimalarials for developing
      countries through public-private partnership. It is currently managing a
      portfolio of around 20 projects at various stages of development. However, as in
      all drug R&D, some of these projects will fail. The portfolio approach helps to
      maximize the chances of success, but there are obvious challenges, including
      financial and managerial ones. Proactive management of the two vital interfaces
      in the drug supply chain is important for success. Upstream, basic research must
      be aligned with translational research in order to ensure a continuous supply of
      leads into the development pipeline. Meanwhile, downstream, drug discovery and
      development must be aligned with access to ensure optimal health impact. All
      stages require partnership, sustainable financing and the engagement of disease
      endemic countries. The recent G8 report on Africa has lent support to mechanisms
      aimed at improving health and achieving the Millenium Development Goals.

PMID- 16085176
TI  - Mitochondria superoxide dismutase mimetic inhibits peroxide-induced oxidative
      damage and apoptosis: role of mitochondrial superoxide.
AB  - The purpose of this study was to test the hypothesis whether Mito-carboxy proxyl
      (Mito-CP), a mitochondria-targeted nitroxide, inhibits peroxide-induced oxidative
      stress and apoptosis in bovine aortic endothelial cells (BAEC). Glucose/glucose
      oxidase (Glu/GO)-induced oxidative stress was monitored by
      dichlorodihydrofluorescein oxidation catalyzed by intracellular H(2)O(2) and
      transferrin receptor-mediated iron transported into cells. Pretreatment of BAECs
      with Mito-CP significantly diminished H(2)O(2)- and lipid peroxide-induced
      intracellular formation of dichlorofluorescene and protein oxidation. Electron
      paramagnetic resonance (EPR) studies confirmed the selective accumulation of Mito
      CP into the mitochondria. Mito-CP inhibited the cytochrome c release and caspase
      3 activation in cells treated with peroxides. Mito-CP inhibited both H(2)O(2)-
      and lipid peroxide-induced inactivation of complex I and aconitase,
      overexpression of transferrin receptor (TfR), and mitochondrial uptake of (55)Fe,
      while restoring the mitochondrial membrane potential and proteasomal activity. In
      contrast, the "untargeted" carboxy proxyl (CP) nitroxide probe did not protect
      the cells from peroxide-induced oxidative stress and apoptosis. However, both CP
      and Mito-CP inhibited superoxide-induced cytochrome c reduction to the same
      extent in a xanthine/xanthine oxidase system. We conclude that selective uptake
      of Mito-CP into the mitochondria is responsible for inhibiting peroxide-mediated
      Tf-Fe uptake and apoptosis and restoration of the proteasomal function.

PMID- 16085177
TI  - Oxidative stress levels are raised in chronic fatigue syndrome and are associated
      with clinical symptoms.
AB  - The aetiology of chronic fatigue syndrome (CFS) is unknown; however, recent
      evidence suggests excessive free radical (FR) generation may be involved. This
      study investigated for the first time levels of 8-iso-prostaglandin-F(2 alpha)
      isoprostanes alongside other plasma markers of oxidative stress in CFS patients
      and control subjects. Forty-seven patients (18 males, 29 females, mean age 48 [19
      -63] years) who fulfilled the Centres for Disease Control classification for CFS
      and 34 healthy volunteers (13 males, 21 females, 46 [19--63] years) were enrolled
      in the study. The CFS patients were divided into two groups; one group had
      previously defined cardiovascular (CV) risk factors of obesity and hypertension
      (group 1) and the second were normotensive and nonobese (group 2). Patients had
      significantly increased levels of isoprostanes (group 1, P=0.007; group 2,
      P=0.03, unpaired t test compared to controls) and oxidised low-density
      lipoproteins (group 2, P=0.02) indicative of a FR attack on lipids. CFS patients
      also had significantly lower high-density lipoproteins (group 1, P=0.011; group
      2, P=0.005). CFS symptoms correlated with isoprostane levels, but only in group 2
      low CV risk CFS patients (isoprostanes correlated with; total symptom score
      P=0.005; joint pain P=0.002; postexertional malaise P=0.027, Pearson). This is
      the first time that raised levels of the gold standard measure of in vivo
      oxidative stress (isoprostanes) and their association with CFS symptoms have been
      reported.

PMID- 16085178
TI  - NADPH oxidase and apoptosis in cerulein-stimulated pancreatic acinar AR42J cells.
AB  - Apoptosis linked to oxidative stress has been implicated in pancreatitis. We
      investigated whether NADPH oxidase mediates apoptosis in cerulein-stimulated
      pancreatic acinar AR42J cells. We report here that cerulein treatment resulted in
      the activation of NADPH oxidase, as determined by ROS production, translocation
      of cytosolic subunits p 47(phox) and p 67(phox) to the membrane, and interaction
      between NADPH oxidase subunits. Cerulein induced Ca(2+) oscillation, the
      expression of apoptotic genes p53 and bax, and apoptotic indices (DNA
      fragmentation, TUNEL staining, caspase 3 activity, decrease in cell viability) in
      AR42J cells. Treatment with a Ca(2+) chelator, BAPTA-AM, or transfection with
      antisense oligonucleotides for NADPH oxidase subunits p22(phox) and p 47(phox)
      inhibited cerulein-induced ROS production, translocation of NADPH oxidase
      cytosolic subunits p 47(phox) and p 67(phox) to the membrane, and the expression
      of apoptotic genes and apoptotic indices, as compared to the cells without
      treatment and those transfected with the corresponding sense oligonucleotides.
      These results indicate that NADPH oxidase may mediate ROS-induced apoptosis in
      pancreatic acinar cells in a Ca(2+)-dependent manner.

PMID- 16085179
TI  - Nitric oxide- and superoxide-dependent mitochondrial signaling in endotoxin
      induced apoptosis in the rostral ventrolateral medulla of rats.
AB  - This study evaluated the hypothesis that the repertoire of cellular events that
      underlie circulatory fatality during endotoxemia may entail mitochondrial
      respiratory enzyme dysfunction, followed by the release of cytochrome c to the
      cytosol that triggers the activation of caspase cascades, leading to apoptotic
      cell death in the rostral ventrolateral medulla (RVLM) where sympathetic premotor
      neurons responsible for maintaining vasomotor tone are located. In adult Sprague
      Dawley rats maintained under propofol anesthesia, nucleosomal DNA fragmentation
      was detected in the RVLM in a temporal profile that coincided positively with the
      progression of cardiovascular depression during experimental endotoxemia induced
      by Escherichia coli lipopolysaccharide (LPS). LPS also induced nitric oxide (NO)
      and superoxide (O(2)(-)) production, depressed mitochondrial Complex I and IV
      activity, promoted the release of cytochrome c from mitochondria to cytosol,
      upregulated the cytosolic expression of activated caspase-9 and -3, or increased
      caspase-3 enzyme activity in the RVLM. Microinjection bilaterally into the RVLM
      of an inducible nitric oxide synthase (iNOS) blocker, S-methylisothiourea, or a
      superoxide dismutase mimetic, Tempol, significantly blunted these apoptotic
      cellular events and antagonized the cardiovascular depression during endotoxemia.
      We conclude that caspase-dependent apoptotic cell death that results from NO- and
      O(2)(-)-associated mitochondrial signaling in the RVLM may underlie fatal
      cardiovascular depression during endotoxemia.

PMID- 16085180
TI  - Effects of N-acetylcysteine on ethanol-induced hepatotoxicity in rats fed via
      total enteral nutrition.
AB  - The effects of the dietary antioxidant N-acetylcysteine (NAC) on alcoholic liver
      damage were examined in a total enteral nutrition (TEN) model of ethanol toxicity
      in which liver pathology occurs in the absence of endotoxemia. Ethanol treatment
      resulted in steatosis, inflammatory infiltrates, occasional foci of necrosis, and
      elevated ALT in the absence of increased expression of the endotoxin receptor CD
      14, a marker of Kupffer cell activation by LPS. In addition, ethanol treatment
      induced CYP 2 E1 and increased TNFalpha and TGFbeta mRNA expression accompanied
      by suppressed hepatic IL-4 mRNA expression. Ethanol treatment also resulted in
      the hepatic accumulation of malondialdehyde (MDA) and hydroxynonenal (HNE)
      protein adducts, decreased antioxidant capacity, and increased antibody titers
      toward serum hydroxyethyl radical (HER), MDA, and HNE adducts. NAC treatment
      increased cytosolic antioxidant capacity, abolished ethanol-induced lipid
      peroxidation, and inhibited the formation of antibodies toward HNE and HER
      adducts without interfering with CYP 2 E1 induction. NAC also decreased ethanol
      induced ALT release and inflammation and prevented significant loss of hepatic
      GSH content. However, the improvement in necrosis score and reduction of TNFalpha
      mRNA elevation did not reach statistical significance. Although a direct
      correlation was observed among hepatic MDA and HNE adduct content and TNFalpha
      mRNA expression, inflammation, and necrosis scores, no correlation was observed
      between oxidative stress markers or TNFalpha and steatosis score. These data
      suggest that ethanol-induced oxidative stress can contribute to inflammation and
      liver injury even in the absence of Kupffer cell activation by endotoxemia.

PMID- 16085181
TI  - Role of reactive oxygen species in zinc deficiency-induced hepatic stellate cell
      activation.
AB  - We previously reported that zinc deficiency caused a reduction in intracellular
      glutathione at 8 h after the addition of zinc chelator, diethylenetriamine
      pentaacetic acid (DTPA), compared with control levels in rat hepatic stellate
      cells. In this study, we investigated the role of reactive oxygen species and
      glutathione on the mechanism of zinc deficiency-induced hepatic stellate cell
      activation, via assessing collagen synthesis. Isolated hepatic stellate cells
      were incubated with or without DTPA. Type I collagen expression in hepatic
      stellate cells was detected by immunohistochemistry, and then quantification of
      the intensity of type I collagen expression was analyzed using a computer with
      NIH image. Intracellular glutathione was measured using HPLC. H(2)O(2) release
      from hepatic stellate cells into the overlying medium was assayed using a
      fluorimetric method. H(2)O(2) release by DTPA-treated hepatic stellate cells
      significantly increased from 4 h, but returned to control levels after zinc
      supplementation. When catalase was added to the culture at 6 h after the addition
      of DTPA, the staining for type I collagen was as weak as at control levels.
      Diphenyliodonium chloride, the inhibitor of NADPH oxidase, produced a marked
      reduction in zinc deficiency-induced H(2)O(2) release. The results of this study
      show that the depletion of intracellular glutathione levels triggers a
      progression of collagen synthesis in zinc deficient-hepatic stellate cells and
      this depletion may be induced by the stimulation of cellular production of
      H(2)O(2).

PMID- 16085182
TI  - Mitochondrial dysfunction in choline deficiency-induced apoptosis in cultured rat
      hepatocytes.
AB  - Our recent studies have demonstrated that generation of ROS is associated with
      choline deficiency (CD)-induced apoptosis in CWSV-1 cells, an immortalized rat
      hepatocyte that becomes tumorigenic by stepwise culturing in decreasing levels of
      choline. In the present study, we investigated the effect of CD on loss of
      mitochondrial membrane potential (MMP), using the JC-1 probe by FASCAN assay. Our
      data demonstrate that MMP in CD-cultured cells was decreased in a time- and dose
      dependent manner and that significant disruption occurred at 24 h, relative to
      high choline (HC, 70 microM) cultured cells. In order to investigate further the
      relationship among the CD-induced ROS, MMP collapse, and apoptosis, we examined
      the effects of different inhibitors on ROS production, MMP disruption, and
      apoptosis in CD or HC-cultured CWSV-1 cells. These data indicate that the
      disruption of MMP is an upstream event in CD-induced apoptosis, and mitochondrial
      dysfunction plays a key role in mediating CD-induced apoptosis in CWSV-1 cells.

PMID- 16085183
TI  - Intracellular generation of reactive oxygen species by contracting skeletal
      muscle cells.
AB  - The aim of this work was to examine the intracellular generation of reactive
      oxygen species in skeletal muscle cells at rest and during and following a period
      of contractile activity. Intracellular generation of reactive oxygen species was
      examined directly in skeletal muscle myotubes using 2',7'
      dichlorodihydrofluorescein (DCFH) as an intracellular probe. Preliminary
      experiments confirmed that DCFH located to the myotubes but was readily
      photoxidizable during repeated intracellular fluorescence measurements and
      strategies to minimize this were developed. The rate of oxidation of DCFH did not
      change significantly over 30 min in resting myotubes, but was increased by
      approximately 4-fold during 10 min of repetitive, electrically stimulated
      contractile activity. This increased rate was maintained over 10 min following
      the end of the contraction protocol. DCF fluorescence was distributed evenly
      throughout the myotube with no evidence of accumulation at any specific
      intracellular sites or localization to mitochondria. The rise in DCF fluorescence
      was effectively abolished by treatment of the myotubes with the intracellular
      superoxide scavenger, Tiron. Thus these data appear to represent the first direct
      demonstration of a rise in intracellular oxidant activity during contractile
      activity in skeletal muscle myotubes and indicate that superoxide, generated from
      intracellular sites, is the ultimate source of oxidant(s) responsible for the
      DCFH oxidation.

PMID- 16085184
TI  - Role of Smac/DIABLO in hydrogen peroxide-induced apoptosis in C2C12 myogenic
      cells.
AB  - Smac/DIABLO was recently identified as a protein released from mitochondria in
      response to apoptotic stimuli which promotes apoptosis by antagonizing inhibitors
      of apoptosis proteins. Furthermore, Smac/DIABLO plays an important regulatory
      role in the sensitization of cancer cells to both immune-and drug-induced
      apoptosis. However, little is known about the role of Smac/DIABLO in hydrogen
      peroxide (H(2)O(2))-induced apoptosis of C2C12 myogenic cells. In this study,
      Hoechst 33258 staining was used to examine cell morphological changes and to
      quantitate apoptotic nuclei. DNA fragmentation was observed by agarose gel
      electrophoresis. Intracellular translocation of Smac/DIABLO from mitochondria to
      the cytoplasm was observed by Western blotting. Activities of caspase-3 and
      caspase-9 were assayed by colorimetry and Western blotting. Full-length
      Smac/DIABLO cDNA and antisense phosphorothioate oligonucleotides against
      Smac/DIABLO were transiently transfected into C2C12 myogenic cells and
      Smac/DIABLO protein levels were analyzed by Western blotting. The results showed
      that: (1) H(2)O(2) (0.5 mmol/L) resulted in a marked release of Smac/DIABLO from
      mitochondria to cytoplasm 1 h after treatment, activation of caspase-3 and
      caspase-9 4 h after treatment, and specific morphological changes of apoptosis 24
      h after treatment; (2) overexpression of Smac/DIABLO in C2C12 cells significantly
      enhanced H(2)O(2)-induced apoptosis and the activation of caspase-3 and caspase-9
      (P<0.05). (3) Antisense phosphorothioate oligonucleotides against Smac/DIABLO
      markedly inhibited de novo synthesis of Smac/DIABLO and this effect was
      accompanied by decreased apoptosis and activation of caspase-3 and caspase-9
      induced by H(2)O(2) (P<0.05). These data demonstrate that H(2)O(2) could result
      in apoptosis of C2C12 myogenic cells, and that release of Smac/DIABLO from
      mitochondria to cytoplasm and the subsequent activation of caspase-9 and caspase
      3 played important roles in H(2)O(2)-induced apoptosis in C2C12 myogenic cells.

PMID- 16085185
TI  - Apples increase nitric oxide production by human saliva at the acidic pH of the
      stomach: a new biological function for polyphenols with a catechol group?
AB  - Dietary inorganic nitrate is secreted in saliva and reduced to nitrite by
      bacterial flora. At the acidic pH of the stomach nitrite is present as nitrous
      acid in equilibrium with nitric oxide (*NO), and other nitrogen oxides with
      nitrating and nitrosating activity. *NO in the stomach exerts several beneficial
      effects, but nitrosating/nitrating species have been implicated as a possible
      cause of epithelial neoplasia at the gastroesophageal junction. We investigated
      the effects of apple extracts on *NO release by human saliva at pH 2. A water
      extract obtained from apple homogenate increased *NO release caused by
      acidification of saliva. Data show that polyphenols were responsible for this
      activity, with chlorogenic acid and (+)-catechin the most active and concentrated
      species. However, ferulic acid, a hydroxycinnamic acid with only one aromatic
      hydroxyl group, did not increase *NO release. Fructose, the most representative
      sugar in apples, was also inactive. Interestingly, ascorbic acid in saliva
      induced a SCN(-)-enhanced burst of *NO but, unlike apple, the release was
      transient. The simultaneous addition of ascorbic acid and apple extract caused a
      burst of *NO followed by the increased steady-state level characteristic of
      saliva containing apple extract. Chlorogenic acid and (+)-catechin, but not
      ferulic acid, formed o-semiquinone radicals and nitrated polyphenols, suggesting
      the scavenging of *NO(2) by o-semiquinones. Our results propose that some apple
      polyphenols not only inhibit nitrosation/nitration but also promote *NO bio
      availabilty at the gastric level, a previously unappreciated function.

PMID- 16085186
TI  - Protective effect of green tea polyphenols on the SH-SY5Y cells against 6-OHDA
      induced apoptosis through ROS-NO pathway.
AB  - Green tea polyphenols (GTP) are thought to help prevent oxidative stress-related
      diseases, such as cancer, cardiovascular disease, neurodegenerative disease, and
      aging. We here investigate the protective mechanisms of GTP on SH-SY5Y cells
      against apoptosis induced by the pro-parkinsonian neurotoxin 6-hydroxydopamine (6
      OHDA). GTP rescued the changes in condensed nuclear and apoptotic bodies,
      attenuated 6-OHDA-induced early apoptosis, prevented the decrease in
      mitochondrial membrane potential, and suppressed accumulation of reactive oxygen
      species (ROS) and of intracellular free Ca(2+). GTP also counteracted the 6-OHDA
      induced nitric oxide increase and overexpression of nNOS and iNOS, and decreased
      the level of protein-bound 3-nitrotyrosine (3-NT). In addition, GTP inhibited the
      autooxidation of 6-OHDA and scavenged oxygen free radicals in a dose- and time
      dependent manner. Our results show that the protective effects of GTP on SH-SY5Y
      cells are mediated, at least in part, by controlling the ROS-NO pathway.

PMID- 16085187
TI  - Inhibition of thioredoxin reductase but not of glutathione reductase by the major
      classes of alkylating and platinum-containing anticancer compounds.
AB  - Mammalian thioredoxin reductase (TrxR) is important for cell proliferation,
      antioxidant defense, and redox signaling. Together with glutathione reductase
      (GR) it is the main enzyme providing reducing equivalents to many cellular
      processes. GR and TrxR are flavoproteins of the same enzyme family, but only the
      latter is a selenoprotein. With the active site containing selenocysteine, TrxR
      may catalyze reduction of a wide range of substrates, but can at the same time
      easily be targeted by electrophilic compounds due to the extraordinarily high
      reactivity of a selenolate moiety. Here we addressed the inhibition of the enzyme
      by major anticancer alkylating agents and platinum-containing compounds and we
      compared it to that of GR. We confirmed prior studies suggesting that the
      nitrosourea carmustine can inhibit both GR and TrxR. We next found, however, that
      nitrogen mustards (chlorambucil and melphalan) and alkyl sulfonates (busulfan)
      efficiently inhibited TrxR while these compounds, surprisingly, did not inhibit
      GR. Inhibitions were concentration and time dependent and apparently
      irreversible. Anticancer anthracyclines (daunorubicin and doxorubicin) were, in
      contrast to the alkylating agents, not inhibitors but poor substrates of TrxR. We
      also found that TrxR, but not GR, was efficiently inhibited by both cisplatin,
      its monohydrated complex, and oxaliplatin. Carboplatin, in contrast, could not
      inhibit any of the two enzymes. These findings lead us to conclude that
      representative compounds of the major classes of clinically used anticancer
      alkylating agents and most platinum compounds may easily target TrxR, but not GR.
      The TrxR inhibition should thereby be considered as a factor that may contribute
      to the cytotoxicity seen upon clinical use of these drugs.

PMID- 16085188
TI  - Widening the window of persistence in seasonal pathogen-host systems.
AB  - Local instability of exploiter-victim systems is well-known in both theory and in
      nature. Victims can be too sparse to support exploiter reproduction (under
      exploitation) or they can be too readily driven to extinction (over
      exploitation). Exploiters of seasonal resources face the additional challenge of
      surviving periods when victims are rare or unavailable. We formulate a fully
      stochastic model of highly seasonal pathogen-host dynamics and explore the
      interactions between an entomopathogenic nematode and its lepidopteran host. Our
      model suggests that if nematode populations experience the high rates of
      mortality predicted by short-term laboratory experiments, the paired threats of
      under- and over-exploitation should preclude the long-term persistence of this
      exploiter-victim system. We measured nematode mortality rates in the field and
      found that long-term mortality is lower than that predicted by short-term
      experiments. Incorporation of this new data into our model produces long-term
      persistence of local nematode populations across a range of initial nematode
      densities.

PMID- 16085189
TI  - Systematic reviews of diagnostic accuracy studies require study by study
      examination: first for heterogeneity, and then for sources of heterogeneity.

PMID- 16085190
TI  - Searching one or two databases was insufficient for meta-analysis of
      observational studies.
AB  - OBJECTIVE: To address methodologic issues in searching for observational studies
      by presenting database search methods and results. STUDY DESIGN AND SETTING:
      Results of two literature searches for publications reporting on observational
      studies of alcohol consumption and the risk of breast cancer and large bowel
      cancer were compared, to evaluate the sensitivity of various bibliographic
      databases and search strategies, including hand-searching reviews and meta
      analyses. RESULTS: The target sensitivity of 90% of publications in the breast
      cancer search was achieved by starting with Medline, then adding Biosis, Embase,
      and SCI EXPANDED-SSCI, which provided a total of 72 (91%) of the 79 relevant
      publications. To reach a similar 89% sensitivity for large bowel cancer, at least
      Biosis, Dissertation Abstracts Online, Embase, ETOH, and Medline had to be
      searched, with the addition of hand search of reviews and meta-analyses.
      CONCLUSION: Limiting a search to one or two databases when conducting meta
      analyses of observational studies will not provide a thorough summary of the
      existing literature. The findings support recommendations to implement a
      comprehensive search of electronic databases and the reference lists of recent
      review articles and meta-analyses.

PMID- 16085191
TI  - The performance of tests of publication bias and other sample size effects in
      systematic reviews of diagnostic test accuracy was assessed.
AB  - BACKGROUND AND OBJECTIVE: Publication bias and other sample size effects are
      issues for meta-analyses of test accuracy, as for randomized trials. We
      investigate limitations of standard funnel plots and tests when applied to meta
      analyses of test accuracy and look for improved methods. METHODS: Type I and type
      II error rates for existing and alternative tests of sample size effects were
      estimated and compared in simulated meta-analyses of test accuracy. RESULTS: Type
      I error rates for the Begg, Egger, and Macaskill tests are inflated for typical
      diagnostic odds ratios (DOR), when disease prevalence differs from 50% and when
      thresholds favor sensitivity over specificity or vice versa. Regression and
      correlation tests based on functions of effective sample size are valid, if
      occasionally conservative, tests for sample size effects. Empirical evidence
      suggests that they have adequate power to be useful tests. When DORs are
      heterogeneous, however, all tests of funnel plot asymmetry have low power.
      CONCLUSION: Existing tests that use standard errors of odds ratios are likely to
      be seriously misleading if applied to meta-analyses of test accuracy. The
      effective sample size funnel plot and associated regression test of asymmetry
      should be used to detect publication bias and other sample size related effects.

PMID- 16085192
TI  - In an empirical evaluation of the funnel plot, researchers could not visually
      identify publication bias.
AB  - BACKGROUND AND OBJECTIVE: Publication bias and related biases can lead to overly
      optimistic conclusions in systematic reviews. The funnel plot, which is
      frequently used to detect such biases, has not yet been subjected to empirical
      evaluation as a visual tool. We sought to determine whether researchers can
      correctly identify publication bias from visual inspection of funnel plots in
      typical-size systematic reviews. METHODS: A questionnaire with funnel plots
      containing 10 studies each (the median number in medical meta-analyses) was
      completed by 41 medical researchers, including clinical research fellows in a
      meta-analysis class, faculty in clinical care research, and experienced
      systematic reviewers. RESULTS: On average, participants correctly identified
      52.5% (95% CI 50.6-54.4%) of the plots as being affected or unaffected by
      publication bias. The weighted mean percent correct, which adjusted for the fact
      that asymmetric plots are more likely to occur in the presence of publication
      bias, was also low (48.3 to 62.8%, depending on the presence or absence of
      publication bias and heterogeneous study effects). CONCLUSION: Researchers who
      assess for publication bias using the funnel plot may be misled by its shape.
      Authors and readers of systematic reviews need to be aware of the limitations of
      the funnel plot.

PMID- 16085193
TI  - Scoring based on item response theory did not alter the measurement ability of
      EORTC QLQ-C30 scales.
AB  - BACKGROUND AND OBJECTIVES: Most health-related quality-of-life questionnaires
      include multi-item scales. Scale scores are usually estimated as simple sums of
      the item scores. However, scoring procedures utilizing more information from the
      items might improve measurement abilities, and thereby reduce the needed sample
      sizes. We investigated whether item response theory (IRT)-based scoring improved
      the measurement abilities of the EORTC QLQ-C30 physical functioning, emotional
      functioning, and fatigue scales. METHODS: Using a database of 13,010 subjects we
      estimated the relative validities of IRT scoring compared to sum scoring of the
      scales. RESULTS: The mean relative validities were 1.04 (physical), 1.03
      (emotional), and 0.97 (fatigue). None of these were significantly larger than 1.
      Thus, no gain in measurement abilities using IRT scoring was found for these
      scales. Possible explanations include that the items in the scales are not
      constructed for IRT scoring and that the scales are relatively short. CONCLUSION:
      IRT scoring of the three longest EORTC QLQ-C30 scales did not improve measurement
      abilities compared to the traditional sum scoring of the scales.

PMID- 16085194
TI  - Clinical comorbidity was specific to disease pathology, psychologic distress, and
      somatic symptom amplification.
AB  - OBJECTIVE: To test the hypothesis that disease pathology, psychologic distress,
      and somatic symptom amplification separately influence health care use by
      investigating the patterns of comorbidity in patients with diabetes, anxiety, and
      upper respiratory tract infection (URTI), respectively. METHODS: Adult diabetes
      (n=4,365), anxiety (13,421), and URTI (9,854) cases, and 15,000 randomly selected
      controls were identified from a 1-year national survey of general practice
      consultations. Comorbidity was based on a standard clinical morbidity
      classification used by general practitioners in actual consultations. RESULTS: In
      case-control analyses of 122 morbidities, the number of significant comorbid
      associations (P<.01) for diabetes was 30, anxiety was 72, and URTI was 49. These
      associations showed significant heterogeneity in the odds ratios estimated using
      Cochran's Q and I2 statistic, both between case groups and within each case
      group. Diabetes associations were stronger with peripheral vascular disease (odds
      ratio 2.7), candidiasis (2.5), cataract (2.4), obesity (2.2), and hypertension
      (1.7); anxiety with depressive disorder (4.1), affective psychosis (4.0),
      adjustment reaction (3.2), functional gastrointestinal disorders (2.5) and
      general symptoms (2.5); and URTI with nonspecific blood findings (5.5),
      bronchitis (5.2), and injury (3.5). CONCLUSION: Our study shows patterns of
      clinical comorbidity specific to the case conditions that supports the hypothesis
      that different mechanisms (disease pathology, psychologic distress, and somatic
      symptom amplification) operate to influence consultation behavior and
      comorbidity.

PMID- 16085195
TI  - Ensuring high accuracy of data abstracted from patient charts: the use of a
      standardized medical record as a training tool.
AB  - BACKGROUND AND OBJECTIVE: The quality and integrity of information is pivotal to
      the validity and reliability of inferences drawn in research. The aim of this
      study is to demonstrate that standardized medical records can be used as a data
      abstraction training tool and a quality control measure to assess the validity of
      medical record data abstraction. METHODS: Sixteen hospitals participating in a
      large multicenter study completed standardized data abstraction forms for three
      representative patient charts, one in each of the clinical areas of postoperative
      critical care and trauma, cardiac surgery, and repair of hip fracture. The
      completed forms were then compared to an established gold standard. RESULTS: The
      mean level of accuracy of the completed data abstraction forms in each of the
      above three clinical areas were 91.8, 77.5, and 91.5%, respectively. Missing data
      accounted for 19% of all discrepancies between the abstracted information and the
      gold standard. If queries and amendments were made by the study's coordinating
      center, the mean level of accuracy increased to 94.5, 82.5, and 92.9%,
      respectively. CONCLUSION: The present study stressed the need for quality control
      measures in abstracting information from medical records to ensure the accuracy
      and completeness of the data abstracted.

PMID- 16085196
TI  - Measures of adherence based on self-report exhibited poor agreement with those
      based on pharmacy records.
AB  - OBJECTIVE: To assess the level of agreement between a self-reported measure of
      adherence with prescribed drug and a measure of adherence based on pharmacy data.
      METHODS: During an in-home interview, people aged 65+ were asked to report all
      prescription drugs they had taken in the preceding month. For each drug, a four
      item questionnaire was used to determine self-reported adherence. In the pharmacy
      records, each drug that had been filled at least four times was analyzed, and the
      percentage of days with the drug available was calculated. Two types of adherence
      were studied: (1) adherence by individual, and (2) adherence by drug. The level
      of agreement was assessed using kappa (kappa) statistics and proportions of
      agreement. RESULTS: We compared the adherence measures among 189 individuals (880
      drugs). Among all, 90 individuals (48%) self-reported adherence, whereas 95
      individuals (50%) were adherent according to the records. The level of agreement
      between these two measures was slight (kappa=0.16 [95% CI: 0.02-0.30]).
      Individuals self-reported to be adherent for 81% of the drugs, while pharmacy
      records showed adherence for 83% of them (kappa=0.13 [95% CI: 0.05-0.20]).
      CONCLUSION: Self-reported measures of adherence exhibited poor agreement with
      those based on pharmacy records.

PMID- 16085197
TI  - Risks and benefits of population-based genetic testing for Mendelian subsets of
      common diseases were examined using the example of colorectal cancer risk.
AB  - OBJECTIVE: Genetic testing for adult-onset, common diseases is becoming more
      commonplace in clinical medicine. We modeled the proportions of hypothetic
      populations that would potentially benefit or suffer harm from widespread
      predisposition testing. METHODS: Using the traditional two-by-two table from the
      discipline of epidemiology, we modeled three hypothetic populations using the
      example of genetic testing for hereditary colorectal cancer in three groups: the
      general population, a genetically increased-risk population, and a population at
      increased risk due to nongenetic factors. RESULTS: We demonstrate that the
      potential benefits are increased and risks are reduced when testing is limited to
      those at increased genetic risk when compared with testing in the general
      population. Where disease incidence is increased due to nongenetic factors,
      genetic testing has the potential to detract from the detection and reduction of
      other potentially important risk factors. CONCLUSION: While targeted testing can
      benefit those truly at increased risk, broadly applied genetic testing can do
      more harm than good.

PMID- 16085198
TI  - The use of additional imaging increased specificity and decreased sensitivity in
      screening mammography.
AB  - BACKGROUND AND OBJECTIVES: To examine the use of additional imaging after
      standard mammographic screening views to better understand the value of these
      additional testing in improving accuracy. MATERIALS AND METHODS: Statewide
      population data on screening mammography were used to report accuracy measures at
      screening and after additional imaging tests. Pathology data from biopsies
      performed within 1 year following the screening mammogram were used to determine
      cancer outcome (489 in situ and invasive cancers). Pathologic and population
      characteristics of women receiving different types of imaging were assessed by
      chi-square or t-tests. Similar tests compared women with the same imaging and
      differing outcomes. RESULTS: Of 77,799 women with screening mammograms 9.9% had
      additional imaging. Additional imaging reduced false positives from 7,765
      (100/1,000 mammograms) to 1,112 (14/1,000 mammograms). The majority of false
      negatives (82%) occurred in women receiving only screening views, and additional
      imaging increased the number of false negatives from 82 (1/1,000 mammograms) to
      115 (1.5/1,000 mammograms). CONCLUSION: Additional imaging can reduce unnecessary
      biopsy but at the cost of some additional false negatives. Additional imaging's
      potential for improving the sensitivity of screening is limited because most
      missed cancers occur in women who do not have additional imaging.

PMID- 16085199
TI  - A risk score predicted coronary heart disease and stroke in a Chinese cohort.
AB  - BACKGROUND AND OBJECTIVE: This article aims to address two issues: first, whether
      risk scores derived from Caucasian cohorts can accurately predict coronary heart
      disease (CHD) in a Chinese population; second, derivation and validation of a new
      risk prediction score for cardiovascular disease (CVD) from a Chinese cohort.
      METHODS: A cohort of 4,400 male steelworkers (18-74 years old) recruited between
      1974-1980 was followed up for an average 13.5 years. A Cox model was used to
      predict 10 year risk of CHD, ischemic, and hemorrhagic stroke based on blood
      pressure, age, total cholesterol, body mass index, and smoking status. RESULTS:
      The prediction rule from the European Recommendations greatly overestimates the
      risk of CHD in Orientals. The new models had good predictive ability, with the
      area under receiver operating characteristic curves (AUCs area) in the derivation
      set being 0.76, 0.72, and 0.82 for CHD, ischemic, and hemorrhagic stroke
      separately; AUCs in the validation set were equally good, at 0.76, 0.78, and
      0.82, respectively. CONCLUSION: The risk stratification rules derived from
      Caucasian cohorts overestimates the CHD risk in Orientals, and we derive a
      specific risk stratification rule for CHD, ischemic and hemorrhagic stroke for
      Chinese men.

PMID- 16085200
TI  - Initial nonresponders had an increased response rate after repeated questionnaire
      mailings.
AB  - BACKGROUND AND OBJECTIVE: There is a growing evidence base on methods to improve
      response rates in surveys among patients. This study aimed to determine the
      additional effect of two intensive follow-up procedures compared to a simple
      follow-up procedure. METHODS: Randomized controlled trial that compared repeated
      mailing of the questionnaire and a request to explain nonparticipation with a
      simple reminder card. The study population comprised 955 elderly adults
      registered with 26 general practitioners in The Netherlands. RESULTS: A total of
      530 adults (56%) returned the questionnaire within 3 weeks and a total of 640
      (67%) after follow-up. Repeated mailing of the questionnaire had additional
      effect compared to the simple reminder card in the group of initial nonresponders
      (relative risk=1.60, 95% confidence interval: 1.11-2.31), but not regarding the
      overall response rate. A request to explain nonparticipation did not have
      additional effect. CONCLUSION: Repeated mailing of the questionnaire increased
      the effectiveness of follow-up among initial nonresponders.

PMID- 16085201
TI  - The near-miss maternal morbidity scoring system was tested in a clinical setting
      in Brazil.

PMID- 16085203
TI  - Obstetric intervention to shorten gestational duration is better decided based on
      conventional measures of gestational age-specific mortality without calculating
      fetuses at risk.

PMID- 16085205
TI  - Inhalation pharmacokinetics of ethylbenzene in B6C3F1 mice.
AB  - The objective of the present study was to characterize the inhalation
      pharmacokinetics of ethylbenzene (EB) in male and female B6C3F1 mice following
      single and repeated exposures. Initially, groups of 28 male and female mice were
      exposed for 4 h to 75, 200, 500, or 1000 ppm in order to determine potential non
      linearity in the kinetics of EB. Then, groups of male and female mice were
      exposed for 6 h to 75 ppm and 750 ppm (corresponding to the NTP exposures) for 1
      or 7 consecutive days, to evaluate whether EB kinetics was altered during
      repeated exposures, The maximal blood concentration (Cmax; mean+/-SD, n=4)
      observed in female mice at the end of a 4-h exposure to 75, 200, 500, and 1000
      ppm was 0.53+/-0.18, 2.26+/-0.38, 19.17+/-2.74, and 82.36+/-16.66 mg/L,
      respectively. The areas under the concentration vs. time curve (AUCs) following 4
      h exposure to 75, 200, 500, and 1000 ppm were 88.5, 414.0, 3612.2, and 19,104.1
      mg/L/min, respectively, in female mice, and 116.7, 425.7, 3148.3, and 16,039.1
      mg/L/min in male mice. The comparison of Cmax and the kinetic profile of EB in
      mice exposed to 75 ppm suggests that they are similar between 1-day and 7-day
      exposures. However, at 750 ppm, the rate of EB elimination would appear to be
      greater after repeated exposures than single exposure, the pattern being evident
      in both male and female mice. Overall, the single and repeated exposure
      pharmacokinetic data collected in the present study suggest that EB kinetics is
      saturable at exposure concentrations exceeding 500 ppm (and therefore at 750 ppm
      used in the NTP mouse cancer bioassay) but is in the linear range at the lower
      concentration used in the bioassay (75 ppm). These data suggest that
      consideration of the nature and magnitude of non-linear kinetics and induction of
      metabolism during repeated exposures is essential for the conduct of a
      scientifically sound analysis of EB cancer dose-response data collected in B6C3F1
      mice.

PMID- 16085206
TI  - Competence to give informed consent in acute psychosis is associated with
      symptoms rather than diagnosis.
AB  - To investigate the association between competence to give informed consent to
      treatment, specific symptomology and diagnostic category, 110 inpatients
      diagnosed with DSM-IV acute schizophrenia (n = 64), schizoaffective disorder (n =
      25) and bipolar affective disorder (n = 21) were interviewed using the MacArthur
      Competence Assessment Tool for Treatment (MacCAT-T) and the Positive and Negative
      Syndrome Scale (PANSS). Results indicated no significant difference in competence
      between the three disorders. Elevated positive, cognitive and excitement PANSS
      factor scores had lower MacCAT-T scores. Further analyses indicated symptoms that
      impair cognition; particularly, conceptual disorganisation and poor attention
      were most consistently related to poor performance on competence tests.

PMID- 16085207
TI  - Cognitive predictors of psychosocial functioning outcome in schizophrenia: a
      follow-up study of subjects participating in a rehabilitation program.
AB  - The aims of this prospective study were to explore in subjects with psychosis
      participating in a rehabilitation program whether cognitive performances at
      baseline predicted (i) psychosocial functioning over a 15-16 month follow-up;
      (ii) improvement in psychosocial functioning over the rehabilitation program.
      Visuo-spatial tests from the Cambridge Neuropsychological Test Automated Battery
      (CANTAB) were administered to assess cognitive performance in 55 subjects with
      schizophrenia spectrum disorders who completed a rehabilitation program. The
      Multnomah Community Ability Scale (MCAS) was used to measure dimensions of
      community functioning. One subscale of the Client's Assessment of Strengths,
      Interests, and Goals (CASIG) provided a measure of subjective quality of life
      (QoL). Improvement was defined as a 15% or more increase in psychosocial scores
      between baseline and follow-up. Worse baseline sustained attention predicted
      better self-rated quality of life, and better baseline visual memory predicted
      better community functioning over the rehabilitation follow-up period, in
      particular, higher autonomy in activities of daily living, and less physical and
      psychiatric symptoms that could interfere with rehabilitation. Baseline cognitive
      performances predicted community functioning improvement during the follow-up
      period: visual memory predicted improvement in daily living autonomy and in
      social competence; sustained attention predicted improvement in behavioral
      problems (such as medication compliance, collaboration with treatment providers
      or impulse control) and social competence; planning performances predicted
      improvement in social competence. These cognitive functions could be specifically
      targeted in a rehabilitation program aimed at enhancing functioning in those
      particular dimensions.

PMID- 16085208
TI  - Activation of cellular functions in macrophages by venom secretory Asp-49 and Lys
      49 phospholipases A(2).
AB  - The in vitro effects of myotoxin III (MT-III), an Asp-49 catalytically-active
      phospholipase A(2), and myotoxin II (MT-II), a catalytically-inactive Lys-49
      variant, isolated from Bothrops asper snake venom, on phagocytosis and production
      of hydrogen peroxide (H(2)O(2)) by thioglycollate-elicited macrophages were
      investigated. MT-II and MT-III were cytotoxic to mouse peritoneal macrophages at
      concentrations higher than 25 microg/ml. At non-cytotoxic concentrations, MT-II
      stimulated Fcgamma, complement, mannose and beta-glucan receptors-mediated
      phagocytosis, whereas MT-III stimulated only the mannose and beta-glucan
      receptors-mediated phagocytosis. Moreover, both myotoxins induced the release of
      H(2)O(2) by thioglycollate-elicited macrophages, MT-III being the most potent
      stimulator. MT-II induced the release of H(2)O(2) only at a concentration of 3.2
      microg/ml (130% increment) while MT-III induced this effect at all concentrations
      tested (0.5-2.5 microg/ml; average of 206% increment). It is concluded that, at
      non-cytotoxic concentrations, MT-II and MT-III activate defense mechanisms in
      macrophages up regulating phagocytosis, mainly via mannose and beta-glucan
      receptors, and the respiratory burst.

PMID- 16085209
TI  - Study of an outbreak of ciguatera fish poisoning in Hong Kong.
AB  - Ciguatera fish poisoning (CFP) has been a significant and increasing public
      health problem in Hong Kong since 1980s. With growing demand for imported live
      coral fishes, the number of people who suffered from this disease has also been
      increasing. An outbreak of CFP in 2004 was the second most prominent in record as
      compared with the most significant one that occurred in 1998. In 2004, out of a
      total of 823 reported food poisoning outbreaks involving 3159 persons, 65
      incidents (7.9%) affecting 247 people (7.8%) were attributed to CFP. Validated
      mouse bioassay analysis of surveillance samples revealed that seven samples (13%)
      were confirmed to be contaminated with ciguatoxins (CTXs). Typical symptoms of
      CTXs were found in mice injected with 20mg of fish extracts. The causative fishes
      included Cheilinus undulatus, Epinephelus coioides, Plectropomus areolatus, and
      Plectropomus leopardus. Most of these CTX-positive samples analyzed had only
      trace amounts of CTXs in their extract, except a C. undulatus sample which
      contained a mice lethal dose (2.5MU/20mg ether extract). This fish species was
      also the major origin of coral fish that caused clusters of CFP in the last
      quarter of 2004. Cigua-Check analysis of 20 flesh grains from seven CTX-positive
      fishes, previously confirmed as CTX-positive samples by mouse bioassay, showed
      that 50% of flesh grains were CTX contaminated.

PMID- 16085210
TI  - Etiology of community acquired pneumonia among adult patients requiring
      hospitalization in Taiwan.
AB  - BACKGROUND: There has not been a comprehensive multi-center study investigating
      the microbial profile of community acquired pneumonia (CAP) in Taiwan. METHODS: A
      prospective study of adult CAP patients requiring hospitalization between
      December 2001 and April 2002 was carried out in 13 hospitals in Taiwan. Etiology
      was determined based on laboratory data from blood and sputum cultures plus
      serology from paired serum and urine antigen detection tests. RESULTS: Etiology
      was assigned to 99 (58.9%) of the 168 patients having the most complete data for
      etiology determination, with mixed infection in 21 (12.5%) patients. More than
      half (51.8%) of the patients were>60 years and 63.7% of the patients were males.
      The most common etiologic agent was Streptococcus pneumoniae (40, 23.8%), the
      majority (60%, 24 cases) of which was detected by positive urine antigen test.
      Other common agents included Mycoplasma pneumoniae (24, 14.3%), Chlamydia
      pneumoniae (12, 7.1%), Influenza A virus (11, 6.5%), Klebsiella pneumoniae (8,
      4.8%) and Haemophilus influenzae (8, 4.8%). The prevalence of S. pneumoniae and
      M. pneumoniae was highest in patients>60 years (25/87, 28.7%), and<44 years
      (12/59, 19%), respectively; while K. pneumoniae comprised a larger proportion
      (4/22, 18%) in the 45-59 years group. CONCLUSIONS: S. pneumoniae was the most
      common etiology agent in adult patients hospitalized due to CAP in Taiwan and the
      spectrum of other major pathogens was similar to studies conducted elsewhere in
      the world. Empiric treatment recommendations developed in other parts of the
      world may be appropriately adapted for local use after taking into account local
      resistance profiles. Our data also support the recommendation that urine antigen
      test be added as an adjunct to adult CAP etiology diagnosis protocol.

PMID- 16085211
TI  - Early physiotherapy in the respiratory intensive care unit.
AB  - Physiotherapy is an integral part of the management of patients in respiratory
      intensive care units (RICUs). The most important aim in this area is to enhance
      the overall patient's functional capacity and to restore his/her respiratory and
      physical independence, thus decreasing the risks of bed rest associated
      complications. This article is a review of evidence-based effectiveness of
      weaning practices and physiotherapy treatment for patients with respiratory
      insufficiency in a RICU. Literature searches were performed using general and
      specialty databases with appropriate keywords. The evidence for applying a
      weaning process and physiotherapy techniques in these patients has been described
      according to their individual rationale and efficacy. The growing number of
      patients treated in RICUs all over the world makes this non pharmacological
      approach both welcome and interesting. However, to date, there are only strong
      recommendations concerning the evidence-based strategies to speed weaning. Early
      physiotherapy may be effective in ICU: however, most techniques (postures, limb
      exercise and percussion/vibration in particular) need to be further studied in a
      large population. Evidence supporting physiotherapy intervention is limited as
      there are no studies examining the specific effects of interventions on long-term
      outcome.

PMID- 16085212
TI  - Repeatability of standardised nasal nitric oxide measurements in healthy and
      asthmatic adults and children.
AB  - Several nasal nitric oxide (NO) measurement techniques have been described, but
      there is not a widespread measurement technique for measurement of nasal NO. In
      this study we evaluated the repeatability of one technique of nasal NO
      measurements using the nasal application of the NIOX system. METHODS: Three nasal
      NO measurements (NIOX Nitric Oxide Monitoring System, Aerocrine, Sweden) were
      made on a single occasion in 22 healthy subjects and 27 patients with asthma,
      aged 5-69 years. Nasal NO was sampled during breath hold from one nostril at a
      flow rate of 5 ml/s. RESULTS: The repeatability of nasal NO assessed by the
      coefficient of variation (CV) was 12.5% (95% Confidence interval (CI) 11.0-14.7%)
      for the total population. Healthy adults had a significantly better repeatability
      than healthy children (P<0.008). The mean NO level for the total population was
      837 ppb. The mean NO levels in children were lower than in the adults (751 and
      897 ppb, respectively). The mean breath hold length needed to obtain a steady NO
      plateau for all subject categories combined was 20.4+/-6.01 s. The average number
      of attempts needed to obtain three approved NO measurements was 5.4 (range 3-13)
      for the total population. There were no significant differences between the
      different subject categories. When using two measurements per session instead of
      three, the overall CV was 10.5% (95% CI 8.8-13.1%). Most subjects found the
      measurements easy to perform and all of them would accept to do the examination
      as a routine. CONCLUSIONS: Nasal NO measurements in NIOX may provide a useful
      reliable clinical tool to assess and monitor upper airways in different diseases,
      for example PCD and rhinitis, and are acceptable by both healthy and asthmatic
      adults and children, as a part of their routine visit to a physician.

PMID- 16085213
TI  - Essential roles of angiotensin II in vascular endothelial growth factor
      expression in sleep apnea syndrome.
AB  - BACKGROUND: Hypoxia-induced endothelial cell dysfunction has been implicated in
      increased cardiovascular disease associated with obstructive sleep apnea syndrome
      (OSAS). OSAS mediates hypertension by stimulating angiotensin II (Ang II)
      production. Hypoxia and Ang II are the major stimuli of vascular endothelial
      growth factor (VEGF), which is a potent angiogenic cytokine and also contributes
      to the atherogenic process itself. METHODS AND RESULTS: We observed serum Ang II
      and VEGF levels and peripheral blood mononuclear cell (PBMC) and neutrophil VEGF
      expression. Compared to controls, subjects with OSAS had significantly increased
      levels of serum Ang II and VEGF and VEGF mRNA expression in their leukocytes. To
      examine whether Ang II stimulates VEGF expression in OSAS, we treated PBMCs
      obtained from control subjects with Ang II and with an Ang II receptor type 1
      (AT(1)) blocker, olmesartan. We observed an increased expression of VEGF in the
      Ang II-stimulated PBMCs and decreased in VEGF mRNA and protein expression in the
      PBMCs treated with olmesartan. CONCLUSIONS: These findings suggest that the Ang
      II-AT(1) receptors pathway potentially are involved in OSAS and VEGF-induced
      vascularity and that endothelial dysfunction might be linked to this change in
      Ang II activity within leukocytes of OSAS patients.

PMID- 16085214
TI  - Validation of a new method to measure hydrogen peroxide in exhaled breath
      condensate.
AB  - Inflammatory processes in the lung can or will elicit oxidative stress. The
      degree of oxidative stress can be determined by measuring hydrogen peroxide
      (H(2)O(2)) concentration in exhaled breath condensate (EBC) but the methods to
      measure H(2)O(2) are all rather time consuming and only reliable and/or accurate
      in the hand of skilled technicians in a dedicated laboratory. We tested a new
      commercial device (Ecocheck), developed to offer a less time-consuming method to
      measure H(2)O(2). We validated this new method according the NCCLS EP10-A2
      protocol. The validation shows that the imprecision in the low range is high
      (28.4%) and declines with higher concentrations of H(2)O(2) (up to 6.6%). The
      Ecocheck is "an easy to use" measuring device for routine measurements getting
      quick results without the need for skilled technicians to determine H(2)O(2)
      concentrations.

PMID- 16085215
TI  - Is maternal smoking more determinant than paternal smoking on the respiratory
      symptoms of young children?
AB  - BACKGROUND: It is generally accepted that maternal smoking has more detrimental
      effects than paternal smoking on the respiratory health of children. The
      objective of this study was to assess the effects of postnatal exposure due to
      the smoking behaviour by father and mother in the home, and prenatal exposure
      from maternal smoking during pregnancy, on the respiratory symptoms in children.
      METHODS: The parents of 484 children, aged 3-6 years, completed a questionnaire
      about smoking and respiratory symptoms in children. Bivariate and logistic
      regression analyses were used to examine the associated factors with respiratory
      symptoms. RESULTS: The final model of logistic regression analysis showed that
      prenatal exposure by maternal smoking during pregnancy increased the risk of
      wheezing with colds (adjusted OR=2.00, 95% CI:1.13-3.55) with respect to those
      children whose mothers reported no smoking during pregnancy. Postnatal exposure
      by maternal smoking in the home, in the presence of the child, increased the risk
      of cough with phlegm (adjusted OR=2.79, 95% CI:1.23-6.30) with respect to those
      children whose mothers did not smoke in their presence. Paternal smoking was
      associated with wheezing and cough in the bivariate analysis, but did not remain
      significant in the multivariate analysis. CONCLUSIONS: Our results underline a
      greater influence of exposure to maternal smoking (prenatal and postnatal) than
      postnatal paternal smoking on the development of respiratory symptoms in young
      children.

PMID- 16085216
TI  - Comparison of BALF concentrations of ENA-78 and IP10 in patients with idiopathic
      pulmonary fibrosis and nonspecific interstitial pneumonia.
AB  - BACKGROUND: Epithelial neutrophil-activating peptide 78 (ENA-78) and interferon
      gamma-inducible protein 10 (IP10) belong to the CXC chemokine family and are
      considered to be important factors in idiopathic pulmonary fibrosis (IPF).
      Idiopathic nonspecific interstitial pneumonia (NSIP) and IPF are the two largest
      subsets of idiopathic interstitial pneumonias (IIP). In patients with NSIP, the
      prognosis is generally good compared with IPF. Therefore, the pathogenesis of
      NSIP seems to be different from that of IPF, but this remains unclear. The aim of
      the present study was to evaluate the contribution of ENA-78 and IP10 in the two
      diseases. METHODS: We measured the levels of ENA-78 and IP10 in serum and
      bronchoalveolar lavage fluid (BALF) of patients with IPF (n=17), idiopathic NSIP
      (n=10) and healthy subjects (n=12) by enzyme-linked immunosorbent assays.
      RESULTS: The level of ENA-78 in BALF was significantly higher in IPF patients
      than in NSIP patients and controls. Serum levels of ENA-78 and BALF levels of
      IP10 in NSIP patients were significantly higher than in patients with IPF and
      controls. In BALF of patients with NSIP, IP10 level significantly correlated with
      the absolute number of lymphocytes. In IPF patients, BALF IP10 levels also
      correlated with the proportion of lymphocytes in BALF. CONCLUSION: Our results
      show distinct profiles of CXC chemokines in IPF and NSIP, and suggest that these
      chemokines play an important role in inflammatory cell recruitment into the lung
      in patients with IIP.

PMID- 16085217
TI  - Prevalence of psychiatric morbidity in a difficult asthma population:
      relationship to asthma outcome.
AB  - INTRODUCTION: Psychiatric morbidity appears common in fatal and near-fatal asthma
      and may be a factor in difficult to control asthmatic subjects. We examined the
      prevalence of psychiatric morbidity (using psychiatric interview) in a cohort of
      sequentially referred poorly controlled asthmatics and related this to (a) asthma
      outcome (b) assessing chest physician opinion and (c) Hospital Anxiety Depression
      Scale (HADS). METHODS: Patients were evaluated using a systematic evaluation
      protocol to identify and manage all co-morbidity. Psychiatric assessment was
      performed by experienced liaison psychiatrists and ICD10 diagnosis and treatment
      programme assigned. Subjects completed HADS at presentation and follow-up. Asthma
      was managed according to BTS/SIGN Guidelines. RESULTS: Of 65 subjects who
      attended for psychiatric interview, 32 (49%) had an ICD10 diagnosis, (6 (9%)
      previously identified) with depression most common (59%). Physician assessment
      had poor discrimination for psychiatric illness. Anxiety scores (13.4+/-0.8 vs.
      8.5+/-0.7) and depression scores (10.2+/-0.7 vs. 4.8+/-0.5) scores were
      significantly higher in subjects with ICD10 diagnosis (P<0.001), who were also
      more likely to be current smokers (P<0.01). HADS had a poor positive predictive
      value for psychiatric illness but a good negative predictive value for
      depression. There was no relationship between ICD10 diagnosis and asthma outcome.
      Subjects identified as therapy-resistant asthma after systematic evaluation, had
      significantly lower depression scores after treatment (P<0.05). CONCLUSION: In
      difficult asthmatics, there is a high prevalence of undiagnosed psychiatric
      morbidity, with depression being particularly prevalent. A simple screening
      questionnaire such as HADS, has a high false positive rate when compared to
      psychiatric interview, but may be useful in excluding depressive illness. There
      appears to be little association between identification and management of co
      existent psychiatry morbidity and asthma outcome.

PMID- 16085218
TI  - Spontaneous pneumomediastinum long-term follow-up.
AB  - BACKGROUND: Spontaneous pneumomediastinum (SP) is a rare disorder. METHODS: The
      objective of this study is to examine a series of patients treated during 19
      years, analyzing risk, clinical, and diagnostic factors as well as treatment and
      long-term follow-up. MATERIALS AND METHODS: A descriptive, retrospective study
      was done from 1984 to 2003 on 32 patients admitted to the hospital with SP.
      RESULTS: The average age was 21.4+/-6.1 years, 24 (75%) males. 34.4% had
      developed some strain before arriving at the hospital. Nine of the cases were
      asthmatic (28.1%) and another nine were smokers (28.1%). The most frequent
      complaint was thoracic pain, 25 (78.1%). In the physical examination,
      subcutaneous cervical emphysema was observed in 25 patients (78.1%). A simple X
      ray of the thorax was used in the diagnosis of 32 cases. In two patients,
      radiological signs of pneumothorax were discovered. An esophagogram was done on
      two patients but there were no significant findings. All of the cases were
      treated conservatively. The average hospital stay was 3.2+/-1.6 days. No relapses
      were noted in the follow-ups. CONCLUSION: SP is an entity that evolves correctly
      without treatment and has no long-term relapses. Once other occasionally
      associated entities are ruled out, outpatient management can be employed.

PMID- 16085219
TI  - Surfactant protein gene expressions for detection of lung carcinoma cells in
      peripheral blood.
AB  - BACKGROUND: Inflow of tumor cells to circulation is an essential step for
      metastasis of primary tumors. To know its state may contribute to therapeutic
      strategy. However, methodology to detect lung carcinoma cells floating in
      peripheral blood has not been established. Pulmonary surfactant protein (SP)-A,
      SP-C and Clara cells-10 kd protein (CC10) are specific to the lung and often
      expressed in primary lung carcinomas. We evaluated the worth of these gene
      expressions for the detection of carcinoma cells in peripheral blood. METHODS:
      The expressions in 5 ml of venous blood were tested by RT-PCR. Ninety-nine
      patients with non-small cell lung carcinoma (NSCLC) and 17 with small cell lung
      carcinoma (SCLC) were compared to 13 with secondary lung tumor, 48 with non
      malignant respiratory diseases and 19 healthy volunteers. RESULTS: The mRNA
      expressions of SP-A and SP-C were completely specific to NSCLC when compared to
      SCLC and secondary lung tumors. All of the healthy volunteers and patients with
      non-malignant respiratory diseases showed negative for these mRNA expressions,
      except for one sample. The positive rate of SP-A, SP-C and CC10 mRNA in patients
      with NSCLC was 33.3%, 14.1%, 3.3%, respectively. The rates of SP-A and SP-C mRNA
      were higher than that (11.1%) in CEA mRNA. The increased positive rate of mRNA of
      SP-A and SP-C was significantly dependent on the clinical stage and the existence
      of distant metastasis. CONCLUSION: These results demonstrate that the detection
      of mRNA of SP-A and SP-C would give clinicians valuable information suggesting
      the presence of blood-floating carcinoma cells as a step toward metastasis.

PMID- 16085220
TI  - Effect of tumor necrosis factor antagonism on allergen-mediated asthmatic airway
      inflammation.
AB  - OBJECTIVE: To assess whether tumor necrosis factor (TNF) antagonism can attenuate
      eosinophilic airway inflammation in patients with mild-to-moderate allergic
      asthma. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING:
      National Institutes of Health (NIH) Clinical Center. PATIENTS: Twenty-six
      patients with mild-to-moderate allergic asthma, receiving only inhaled beta-2
      agonists, who demonstrated both an early and late phase response to inhalational
      allergen challenge. INTERVENTION: Injection of a soluble TNF receptor (TNFR:Fc,
      etanercept, Enbrel) or placebo, 25mg subcutaneously, twice weekly for 2 weeks,
      followed by a bronchoscopic segmental allergen challenge. MEASUREMENTS: The
      primary outcome measure was whether TNFR:Fc can access the lung and inhibit TNF
      bioactivity. Secondary outcome measures included pulmonary eosinophilia, Th2-type
      cytokines, and airway hyperresponsiveness. RESULTS: Anti-TNF therapy was
      associated with transient hemiplegia in one patient, which resulted in suspension
      of the study. Data from the 21 participants who completed the study were
      analyzed. Following treatment, patients receiving anti-TNF therapy had
      significantly increased TNFR2 levels in epithelial lining fluid (ELF) (P<0.001),
      consistent with delivery of TNFR:Fc to the lung. TNF antagonism did not attenuate
      pulmonary eosinophilia and was associated with an increase in ELF IL-4 levels
      (P=0.033) at 24h following segmental allergen challenge. TNF antagonism was not
      associated with a change in airway hyperresponsiveness to methacholine.
      CONCLUSIONS: TNF antagonism may not be effective for preventing allergen-mediated
      eosinophilic airway inflammation in mild-to-moderate asthmatics. Transient
      hemiplegia, which may mimic an evolving stroke, may be a potential toxicity of
      anti-TNF therapy.

PMID- 16085221
TI  - Etiology and prognostic significance of massive pleural effusions.
AB  - It has been stated that malignancy is the most common aetiology of massive
      pleural effusions. To determine the most frequent causes of massive pleural
      effusions and to assess the diagnostic yield of different diagnostic procedures
      and survival, we prospectively studied 1084 patients with pleural effusion.
      Massive pleural effusions were identified in 121 of 1084 patients (11.2%).
      Compared with non-massive pleural effusions, massive pleural effusions were
      significantly more likely to be malignant (53.7% vs. 38.3%, P=0.03) or secondary
      to cirrhosis (9.9% vs. 2.6%, P=0.0000). On the other hand, massive pleural
      effusions were significantly less likely to be secondary to infection (10.7% vs.
      19.2%, P=0.003) or congestive heart failure (0.8% vs. 6.7%, P=0.03). There was a
      significant increase in the yield of diagnostic studies in patients with massive
      malignant pleural effusions (56.9% for cytological studies and 36.9% for
      biopsies). On the other hand, there was no difference in the diagnostic yield of
      microbiological and histological studies in the group of tuberculous pleural
      effusions. In our study population, patients with non-massive malignant pleural
      effusions had a significantly better survival than those with massive malignant
      pleural effusions, with a median survival of 8 months (95% confidence interval, 7
      9) compared with 5 months (95% confidence interval, 4-6) (P=0.0009). We conclude
      that malignancy is the most common cause of a massive exudative effusion. Massive
      malignant pleural effusions are associated with worse survival, independent of
      age and histologic subgroup, than are non-massive malignant pleural effusions.

PMID- 16085222
TI  - Incipient stage of pulmonary Langerhans-cell histiocytosis complicated with
      pulmonary tuberculosis was examined by high-resolution computed tomography.
AB  - A 29-year-old man with a smoking history of 20 pack years was diagnosed with
      tuberculosis because Mycobacterium tuberculosis was detected in his gastric
      juice. His chest radiograph showed multiple nodular opacities on left upper lobe.
      He was treated with anti-tuberculosis drugs in our hospital. Six months after the
      therapy, he began to complain of dry cough and shortness of breath on exertion.
      Chest radiograph showed reticular opacities in both upper and middle lung fields.
      Multiple thick- and thin-walled bizarre-shaped cysts and ill-defined
      centrilobular opacities were seen mainly in upper and mid-lungs on high
      resolution computed tomography (HRCT). He was diagnosed with pulmonary Langerhans
      cell histiocytosis (PLCH) by transbronchial lung biopsy specimens from right
      upper lobe. HRCT findings before the treatment of tuberculosis were
      retrospectively examined. Several small thin-walled centrilobular cysts were
      scattered in the right upper and middle lung fields without apparent nodular
      lesions. We must consider the possibility of PLCH when these findings are
      detected on HRCT.

PMID- 16085223
TI  - An unusual presentation of hydatid cyst within the soft tissues of the back: re
      investigation of the undiagnosed lung opacity.
AB  - BACKGROUND: Echinococcosis is a zoonotic infection, affecting humans in a
      characteristic geographic distribution. The disease most commonly involves the
      liver and the lung and a soft tissue localization is very rare. METHODS: A case
      of a 68-year-old man, who presented with a cystic lesion on his back, which was
      presumed to be a lipoma or a sebaceous cyst. Surgical excision of the lesion was
      performed. RESULTS: Histopathology revealed a hydatid cyst and with further
      investigations, we identified the nature of a previously undiagnosed opacity in
      the right lung field. Although the patient previously presented with symptoms of
      hydatid cyst rupture (productive cough with haemoptysis), echinococcosis was not
      under consideration. CONCLUSIONS: This unusual case serves to demonstrate that
      echinococcosis, though rare, should be considered in the differential diagnosis
      of cystic lesions in every anatomic location, especially when they occur in
      endemic areas. We overview the diagnosis and treatment of this parasitic
      infection.

PMID- 16085224
TI  - A hypersensitivity pneumonitis case complicated with acute respiratory distress
      syndrome after bronchoscopy.

PMID- 16085225
TI  - A rare complication of pneumonectomy: diagnosis made by a literature search.
AB  - This case describes platypnoea-orthodeoxia syndrome in a patient 2 months after a
      right pneumonectomy for adenocarcinoma of the lung. The patient complained of
      platypnoea (breathlessness in the upright position) and was noted to have
      orthodeoxia (arterial desaturation on standing) on clinical examination. This was
      due to anatomical changes after the pneumonectomy that resulted in direct blood
      flow from the inferior vena cava through a previously unrecognised atrial septal
      defect into the left atrium. The closure of this right to left shunt with an
      Amplatzer occluder produced immediate and striking symptomatic relief in the
      patient. The authors had no previous experience of this very rare complication of
      pneumonectomy. The diagnosis was made after a literature search using
      PubMed/Medline, underlining the direct clinical benefit provided by these
      databases.

PMID- 16085226
TI  - RNA interference directed to CDK2 inhibits HIV-1 transcription.
AB  - We previously reported that cell cycle-dependent kinase 2 (CDK2) is required for
      human immunodeficiency virus-1 (HIV-1) Tat-dependent transcription in vitro. In
      the present study, CDK2-specific RNA interference in cultured HEK293T cells
      inhibited CDK2 expression and Tat-induced HIV-1 transcription from non-integrated
      HIV-1 promoter but not basal HIV-1 transcription or transcription from CMV or
      beta-actin promoters. Also, CDK2-specific RNA interference inhibited Tat-induced
      transcription from the integrated HIV-1 promoter in HeLa-CD4-LTR-beta-gal cells
      and potently blocked TNFalpha-induced HIV-1 viral replication in OM10.1 cells.
      CDK2-specific RNA interference did not have an effect on cell cycle progression,
      but it augmented TNFalpha-induced apoptosis of OM10.1 cells. Our results indicate
      that CDK2 participates in Tat-mediated HIV-1 transcription and may serve as a
      potential therapeutic target.

PMID- 16085227
TI  - Identification of regions of the Beet mild curly top virus (family Geminiviridae)
      capsid protein involved in systemic infection, virion formation and leafhopper
      transmission.
AB  - Plant viruses in the genus Curtovirus (family Geminiviridae) are vectored by the
      beet leafhopper (Circulifer tenellus) and cause curly top disease in a wide range
      of dicotyledonous plants. An infectious clone of an isolate of Beet mild curly
      top virus (BMCTV-[W4]), associated with an outbreak of curly top in pepper and
      tomato crops, was characterized and used to investigate the role of the capsid
      protein (CP) in viral biology and pathogenesis. Frameshift mutations were
      introduced into the overlapping CP and V2 genes, and a series of CP alanine
      scanning mutations were generated. All mutants replicated in tobacco protoplasts
      or systemically infected plants, consistent with these gene products not being
      required for viral DNA replication. The CP frameshift mutant and most C-terminal
      alanine scanning mutants did not systemically infect Nicotiana benthamiana plants
      or form detectable virions, and were not leafhopper-transmitted. In contrast,
      most N-terminal alanine scanning mutants systemically infected N. benthamiana and
      induced disease symptoms, formed virions and were leafhopper-transmissible; thus,
      these substitution mutations did not significantly alter the functional
      properties of this region. One N-terminal mutant (CP49-51) systemically infected
      N. benthamiana, but did not form detectable virions; whereas another (CP25-28)
      systemically infected N. benthamiana and formed virions, but was not insect
      transmissible. These mutants may reveal regions involved in virus movement
      through the plant and/or leafhopper vector. Together, these results indicate an
      important role for virions in systemic infection (long-distance movement) and
      insect transmission, and strongly suggest that virions are the form in which
      BMCTV moves, long distance, in the phloem.

PMID- 16085228
TI  - A cell-free system for the synthesis of Sindbis virus subgenomic RNA: importance
      of the concentration of the initiating NTP.
AB  - We describe here an in vitro system for template-dependent initiation and
      synthesis of a Sindbis virus (SV) subgenomic (SG) RNA transcript. The critical
      components of this system were (1) a minus-strand promoter-template corresponding
      to the region of the SV genome from nt 7441 to nt 7772 (-157 to +175 relative to
      the SG RNA transcription initiation site at nt 7598), and (2) a p15 fraction from
      cells infected with recombinant vaccinia viruses expressing the SV nonstructural
      proteins, P123 and nsP4 (the nsP2 coding region in P123 contained a mutation
      which results in more rapid than normal processing of P123). Our data indicate
      that the SG RNA transcript is of the expected size, of positive polarity, and is
      initiated at the expected site. Changing the +1 nt from A to G, U, or C resulted
      in decreased synthesis of the SG RNA transcript. However, in each case,
      increasing the concentration of the initiating NTP restored synthesis of the
      transcript to the wild-type level. This is the first demonstration of an in vitro
      synthesis of an alphavirus SG RNA transcript which is dependent on the addition
      of an exogenous promoter-template. As such, it will make possible new approaches
      for learning how the synthesis of SG RNA is regulated.

PMID- 16085229
TI  - Eye movements when reading disappearing text: the importance of the word to the
      right of fixation.
AB  - In a series of experiments, the currently fixated word (word n) and/or the word
      to the right of fixation (word n+1) either disappeared or was masked during
      readers' eye fixations. Consistent with prior research, when only word n
      disappeared or was masked, there was little disruption to reading. However, when
      word n+1 either disappeared or was masked (either at the onset of fixation on
      word n or after 60 ms), there was considerable disruption to reading. Independent
      of whether word n and/or word n+1 disappeared or was masked, there were robust
      frequency effects on the fixation on word n. These results not only confirm the
      robust influence of cognitive/linguistic processing on fixation times in reading,
      but also again confirm the importance of preprocessing the word to the right of
      fixation for fluent reading.

PMID- 16085230
TI  - SELDI-TOF-MS: the proteomics and bioinformatics approaches in the diagnosis of
      breast cancer.
AB  - Breast cancer has never had any good serum tumor markers. Therefore, we developed
      and evaluated a proteomics approach to searching for new biomarkers and building
      diagnostic models. SELDI-TOF-MS ProteinChip was used to detect the serum protein
      patterns of 49 breast cancer patients, 51 patients with benign breast diseases,
      and 33 healthy women. The diagnostic models were developed and validated using
      bioinformatics tools such as artificial neural networks and discriminant
      analysis. In total, four models were built and their sensitivities and
      specificities were satisfactory. The abilities of these models to diagnose stage
      I breast cancer were not worse than for stages II-IV (P>0.05). Four candidate
      biomarkers of breast cancer were found. The high sensitivity and specificity
      achieved by this method show great potential for the early detection of breast
      cancer and facilitation of discovering new and improved biomarkers.

PMID- 16085231
TI  - Hyperplasia, reduced E-cadherin expression, and developmental arrest in mammary
      glands oxidatively stressed by loss of mitochondrial superoxide dismutase.
AB  - To investigate the dysregulating effect of excess oxidative stress on mammary
      gland development, mammary anlage from newborn female mice with normal (+/+) or
      absent (null, -/-) manganese superoxide dismutase (SOD2) were excised and
      implanted under the renal capsule of normal host female nude mice with/without
      concurrent estrogen supplementation. After 30 days the transplanted glands were
      excised for wholemount, microscopic and immunohistochemical evaluation. In
      contrast to the normal growth and maturation of transplanted SOD2+/+ glands, SOD2
      /- glands showed arrested development, reduced ductal outgrowth and branching,
      and absent lumen. These hypomorphic SOD2-/- ducts contained hyperplastic
      epithelium with increased Ki-67 labelling, loss of E-cadherin expression, and
      disorganized p63 and cytokeratin (K)-14 expressing basal and myoepithelial
      components. Estrogen treatment failed to upregulate progesterone receptor or
      normalize development. These findings suggest that excess oxidative stress from
      loss of SOD2 function can arrest mammary gland maturation and induce hyperplastic
      epithelium with early premalignant features.

PMID- 16085232
TI  - BRCA1 and BRCA2 germ-line mutations and oral contraceptives: to use or not to
      use.
AB  - Approximately 10% of the cases of breast cancer and invasive ovarian cancer are
      hereditary, occurring predominantly in women with germ-line mutations in the
      BRCA1 or BRCA2 gene. In deciding whether women with germ-line mutations in the
      BRCA1 gene should use oral contraceptives a possible increase in the risk of
      breast cancer needs to be weighed against the convenience of this means of birth
      control and its potential to reduce the risk of ovarian cancer. In women with
      BRCA2 mutations, oral contraceptive use has not been associated with an increased
      risk of breast cancer and does have the potential to reduce the risk of ovarian
      cancer. Prophylactic surgical options and intensified surveillance should, of
      course, be discussed with these patients.

PMID- 16085233
TI  - Categorizing breast mammographic density: intra- and interobserver
      reproducibility of BI-RADS density categories.
AB  - The inter- and intraobserver agreement (kappa-statistic) in reporting according
      to Breast Imaging Reporting and Data System (BI-RADS((R))) breast density
      categories was tested in 12 dedicated breast radiologists reading a digitized set
      of 100 two-view mammograms. Average intraobserver agreement was substantial
      (kappa=0.71, range 0.32-0.88) on a four-grade scale (D1/D2/D3/D4) and almost
      perfect (kappa=0.81, range 0.62-1.00) on a two-grade scale (D1-2/D3-4). Average
      interobserver agreement was moderate (kappa=0.54, range 0.02-0.77) on a four
      grade scale and substantial (kappa=0.71, range 0.31-0.88) on a two-grade scale.
      Major disagreement was found for intermediate categories (D2=0.25, D3=0.28).
      Categorization of breast density according to BI-RADS is feasible and consistency
      is good within readers and reasonable between readers. Interobserver
      inconsistency does occur, and checking the adoption of proper criteria through a
      proficiency test and appropriate training might be useful. As inconsistency is
      probably due to erroneous perception of classification criteria, standard sets of
      reference images should be made available for training.

PMID- 16085234
TI  - The Western Australian gestational breast cancer project: a population-based
      study of the incidence, management and outcomes.
AB  - This descriptive population-based study estimates the incidence, and describes
      the management and outcomes for women diagnosed with gestational breast cancer
      (GBC) aged 15-44 years in Western Australia between January 1982 and December
      2000. Gestational breast cancer accounted for 6.25% of breast cancers in Western
      Australian women less than 45 years of age, and complicated 23.6 per 100,000
      pregnancies. Two thirds were diagnosed postpartum and a third while pregnant. The
      median time from first symptom to diagnosis was less than four weeks. Women
      diagnosed during pregnancy were more likely to have a pregnancy termination. Over
      50% of women were lymph node positive and those diagnosed postpartum were more
      likely to have a mastectomy. Five-year survival was better than reported
      previously (73%). The incidence of GBC was lower than previously reported.
      Significant differences in pregnancy outcome and management exist between the
      pregnant and postpartum groups.

PMID- 16085235
TI  - Histopathological and cell biological characteristics of ductal carcinoma in situ
      (DCIS) of the breast-a comparison between the primary DCIS and subsequent
      ipsilateral and contralateral tumours.
AB  - The rate of ipsilateral local recurrence after ductal carcinoma in situ (DCIS)
      varies (between 5% and 30%) and depends on the type of operation (mastectomy vs.
      breast-conserving operation), and whether postoperative radiotherapy has been
      used. Ipsilateral local recurrence can either emanate from the primary lesion or
      be a new primary tumour. Contralateral lesions may also develop after DCIS. We
      compared histopathological and cell biological characteristics in 37 subsequent
      ipsilateral tumours (25 DCIS and 12 invasive cancers) and 13 subsequent
      contralateral invasive breast cancers with their corresponding primary DCIS. The
      histopathological parameters were re-evaluated and the cell biological factors
      were analysed using conventional immunohistochemical techniques in paraffin
      embedded material. The concordance rate for high grade (nuclear grade 3) vs. non
      high grade (nuclear grades 1+2) between the primary DCIS and the subsequent
      ipsilateral tumour was higher than between the primary DCIS and the subsequent
      contralateral invasive cancer (68% vs. 31%). Similar patterns in the concordance
      rates between the primary DCIS and ipsilateral vs. contralateral tumours were
      also found in the oestrogen receptor status (83% vs. 50%) and the progesterone
      receptor status (87% vs. 58%). The pattern persisted in the other factors
      examined (p53, c-erbB2, bcl-2 and Ki67), although it was less pronounced. The
      overall high rate of concordance in the characteristics between the primary DCIS
      and the subsequent ipsilateral tumours suggests that, in most cases, they
      represent true local recurrences. Subsequent contralateral tumours are more
      likely to be new primary cancers.

PMID- 16085236
TI  - Selective use of post-mastectomy flap irradiation in high-risk breast cancer
      patients.
AB  - The incidence of local recurrence after mastectomy can be reduced by chest wall
      radiotherapy. However, only a minority of patients are at substantial risk. No UK
      national guidelines exist for the use of mastectomy flap radiotherapy. This study
      evaluated a protocol, whereby only high-risk patients were treated with post
      mastectomy flap radiotherapy; identified histologically by grade, vascular
      invasion and nodal status. All women treated by simple mastectomy for invasive
      breast cancer at the Nottingham Breast Unit from January 1993 to December 1995
      were studied (n=292). Postoperative flap radiotherapy was given to 147 high-risk
      women (50.3%). Median follow-up was 76 months. Overall, 12 women (4.1%) developed
      a chest wall recurrence; six were single spot recurrences and the remaining six
      were either multiple spot (n=3) or field change (field change dermal invasion,
      n=3). The chest wall recurrence rate was 2.7% in those treated with radiotherapy.
      A low rate of local recurrence has been achieved with selective use of mastectomy
      flap radiotherapy.

PMID- 16085237
TI  - Docetaxel and cisplatin combination chemotherapy in metastatic breast cancer
      patients with previous exposure to anthracyclines.
AB  - We evaluated the efficacy and safety of the combination of docetaxel and
      cisplatin in metastatic breast cancer (MBC) patients previously treated with
      anthracycline-containing regimens. Between June 1999 and December 2002, 50 female
      MBC patients (median age 43 years; range 29-64) received docetaxel 75 mg/m(2) and
      cisplatin 75 mg/m(2) on day 1 of each 4-week cycle. A total of 226 cycles (median
      four cycles per patient) were administered as first-line (23 patients) or second
      line (27 patients) treatment. Five patients (10%) achieved a complete response
      (CR) and 15 (30%) had partial responses (PR), giving an overall response rate of
      40% (95% CI, 26.4 approximately 53.6%). The median duration of response was 6.1
      months (range, 2.3 approximately 29.2(+) months). With a median follow-up of 15.9
      months, median time to progression was 6.2 months (range 1 approximately 22.5(+)
      months). Toxicities included grades III and IV neutropenia in nine (18%) and ten
      (20%) patients, respectively, and febrile neutropenia in seven patients (14%). In
      conclusion, our data show that docetaxel plus cisplatin is effective with the
      manageable toxicity profile in MBC patients previously treated with
      anthracyclines.

PMID- 16085238
TI  - The impact of the physician on the accrual to randomized clinical trials in
      patients with primary operable breast cancer.
AB  - Randomized clinical trials (RCT) are the best way to define optimal treatment,
      but the accrual rates for hardly any trials have been reported. We analyzed
      retrospectively the participation of patients in eight phase III multicenter
      RTCs. Out of a total of 738 patients treated in a single institution for operable
      breast cancer over a 3-year period, 455 patients (62%) were eligible for at least
      one of the ongoing trials. Overall, 81% of the patients were informed and 47% of
      the eligible patients consented to participate. The accrual was 100% to a study
      with an aggressive combined modality treatment arm for patients with a poor
      prognosis. A low accrual rate was seen in two trials: 6% in the "elderly" trial
      comparing tamoxifen only with mastectomy and 10% to the "axilla" trial comparing
      surgery with radiotherapy to the axilla. The clinicians failed to inform most of
      these patients about the two trials. In the literature seven of the eight trials
      were reported; two of them (29%) failed to accrue enough patients.

PMID- 16085239
TI  - Intracystic papillary carcinoma of the breast in a male patient diagnosed by core
      needle biopsy: a case report.
AB  - We report a case of intracystic papillary carcinoma (IPC) of the breast in a 71
      year-old man in whom diagnosis was made by core needle biopsy. He came to our
      hospital complaining of a left subareolar mass. Imaging diagnosis was a cyst with
      an intracystic component. Since aspiration biopsy cytology was interpreted as a
      borderline lesion, the decision was made to proceed with core needle biopsy.
      Pathological examination of the specimen revealed the intracystic component to be
      non-invasive papillary carcinoma. So the patient underwent simple mastectomy
      without axillary node biopsy. From the final pathological result, no invasion was
      identified.

PMID- 16085240
TI  - Is complete axillary lymph node dissection neccessary in T1 stage invasive pure
      tubular carcinomas of the breast?
AB  - The purpose of this study was to evaluate the frequency of axillary lymph node
      metastasis in invasive pure (not mixed) tubular carcinomas of the breast and to
      compare our results to other series published in the literature. We analyzed 16
      cases of pure tubular carcinoma measuring 2 cm or less in diameter from our
      database from 1988 to 2004 diagnosed in lumpectomy and mastectomy specimens with
      associated axillary lymph node dissection. Histopathologic features were reviewed
      in all patients. In all cases, no axillary lymph node metastasis was observed
      (0%). These data slightly differ from the results of some studies recently
      published in the literature, in which the overall nodal involvement in pure
      tubular carcinomas ranges from 0% to 20%. We conclude that in invasive pure
      tubular carcinomas of the breast measuring less than 2 cm in diameter, complete
      axillary lymph node dissection should be avoided, and we propose a sentinel lymph
      node analysis instead.

PMID- 16085241
TI  - Tumour size distribution in mammography screening.
AB  - Many mammography screening programmes have not been able to show higher
      percentages of small invasive cancers detected at subsequent screens than at
      initial screens. This has been a matter of serious concern as it contradicts the
      very theory of screening. Based on data from the county of Fyn, Denmark we
      evaluated the distribution based on point estimates, as well as on the entire
      tumour size distribution. The programme changed the amount of tumours less than
      15 or 20 mm, but did not change the amount of tumours less than 10 mm. We
      evaluated the entire tumour size distribution and found that screen number was
      the only significant factor, implying that the number of screens changed the
      tumour size distribution. We recommend that the entire tumour size distribution
      is used to evaluate the ability of a programme to detect small breast cancers,
      instead of only point estimates as has previously been the practice.

PMID- 16085242
TI  - Effects of sulfate on anaerobic chloroethene degradation by an enriched culture
      under transient and steady-state hydrogen supply.
AB  - Complete anaerobic dechlorination of chlorinated solvents such as trichloroethene
      (TCE) is essential for bioremediation of chloroethene-contaminated sites. We
      studied the influence of sulfate on microbial dechlorination of TCE to ethene
      both under transient and steady-state conditions, encompassing the range of
      hydrogen (H2) levels commonly found at contaminated sites. The results show that
      sulfate at a concentration of 2.5 mM limits microbial dechlorination by a mixed
      anaerobic culture by reducing the rate under steady-state hydrogen supply (a few
      nM H2), implying a H2 limited dechlorination. Conversely, sulfate did not affect
      dechlorination when rapid fermentation of lactate resulted in transient buildup
      of H2 to levels around two orders of magnitude higher compared to steady-state
      conditions. This has important implications both for optimizing culture
      conditions for dehalogenating microorganisms and for the efficiency of cleanup
      strategies. Our findings may contribute to the understanding and bioremediation
      of chloroethene contaminated environments containing sulfate.

PMID- 16085243
TI  - Hyperthermia after cardiac surgery: mechanism and importance.

PMID- 16085244
TI  - Postoperative hyperthermia following off-pump versus on-pump coronary artery
      bypass surgery.
AB  - OBJECTIVE: Hyperthermia is common in the first 24 hours following coronary artery
      bypass graft surgery (CABG) with cardiopulmonary bypass (CPB). An inflammatory
      response to CPB is often implicated in the pathophysiology of this fever. Unlike
      CABG with CPB, the temperature pattern after off-pump CABG (OPCAB), where CPB is
      avoided, has not yet been described. The purpose of this study was to describe
      the postoperative temperature pattern following OPCAB and to compare it with that
      following on-pump cardiac surgery. DESIGN: Retrospective, observational study.
      SETTING: Tertiary care university hospital. PARTICIPANTS: Consenting patients
      undergoing CABG or OPCAB procedures. INTERVENTIONS: Observational. MEASUREMENTS
      AND MAIN RESULTS: Of the CABG patients, 89% had temperature elevations above 38
      degrees C, versus 44% of the OPCAB patients (P = 0.04). Peak body temperature was
      higher in the on-pump patients (CABG 38.5 degrees C +/- 0.4 degrees C versus
      OPCAB 37.9 degrees C +/- 0.5 degrees C; P = 0.002), as was the area under the
      curve for temperatures greater than 38 degrees C (CABG 1.6 +/- 1.7 degrees C/hr
      versus OPCAB 0.4 +/- 1.2 degrees C/hr; P = 0.02). CONCLUSIONS: Off-pump CABG
      surgery patients experience less hyperthermia compared with on-pump CABG
      patients. The reasons for a lower incidence and severity of hyperthermia after
      OPCAB surgery are not known, but may be related to a reduced inflammatory
      response.

PMID- 16085245
TI  - Infectious complications after cardiac surgery: lack of association with fresh
      frozen plasma or platelet transfusions.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of perioperative
      transfusion of platelets and fresh frozen plasma (FFP) on infection rates after
      cardiac surgery. DESIGN: Retrospective study comparing infection rates after
      cardiac surgery among patients receiving combinations of packed red blood cells
      (PRBCs), platelets, and FFP. SETTING: Tertiary care university teaching hospital.
      PARTICIPANTS: All elective primary coronary artery bypass (CABG) surgery patients
      from July 1995 to January 1998 before introduction of leukocyte-reduced blood
      products. INTERVENTIONS: Multivariate logistic and linear regression models were
      applied to identify clinical risk factors for postoperative infection and to
      determine the relationship between perioperative administration of PRBCs,
      platelets, and FFP with postoperative infection. MEASUREMENTS AND MAIN RESULTS:
      Transfusion of PRBCs, diabetes, age, preoperative hematocrit, and the duration of
      cardiopulmonary bypass were significantly associated with postoperative
      infection; platelet or FFP transfusion added no additional risk to PRBC
      transfusion alone. CONCLUSIONS: Infectious complications in a population of adult
      primary CABG surgery patients were not increased by transfusion of platelets or
      FFP. It is PRBC transfusion that confers an increased risk of postoperative
      infection in this population.

PMID- 16085246
TI  - Active infectious endocarditis: postoperative outcome.
AB  - OBJECTIVE: Many changes have occurred in the natural history and the management
      of active infectious endocarditis (AIE) in recent years. Therefore, the records
      of patients admitted in a tertiary care specialized hospital presenting with the
      Duke criteria were reviewed. METHODS: Adults operated on to treat AIE were
      included during a 3-year period. Patients presenting with AIE associated with a
      pacemaker were not included. Bacteriologic investigations included blood
      cultures, intraoperative samplings (including polymerase chain reaction), and
      serologies. Clinical and bacteriologic factors associated with hospital mortality
      were studied by univariate regression analysis (p < 0.05). RESULTS: Ninety-eight
      of 164 patients (60%) admitted with the diagnosis of AIE underwent valvular
      surgery. The duration between the beginning of AIE and surgery was 23 +/- 16
      (mean +/- standard deviation) days. Only 45 patients had a previous history of
      valvular disease. Seventy-two patients presented with aortic and 41 with mitral
      valve AIE. Fifty suffered from embolic events. Streptococcus species were
      responsible in 64 cases (23 were Streptococcus bovis) and Staphylococcus species
      in 24 cases. Death occurred postoperatively in 19 patients. The factors
      associated with fatal outcome were preoperative hemodynamic instability, age,
      Parsonnet and Simplified Acute Physiology Score II scores, diabetes mellitus,
      preexisting valvulopathy, antiarrhythmic treatment, hypoalbuminemia, renal
      dysfunction, duration of extracorporeal circulation, and red cell allogeneic
      transfusions. The type of bacteria did not influence mortality. The mean
      intensive care unit and hospital stays were 10 and 39 days, respectively. Eleven
      patients suffered from neurologic sequelae; 2 years later, 2 of them presented
      with severe deficit and 1 had died. CONCLUSIONS: AIE necessitating cardiac
      surgery should be considered as a severe and resource-consuming disease.

PMID- 16085247
TI  - Clinical experience with polyclonal IgM-enriched immunoglobulins in a group of
      patients affected by sepsis after cardiac surgery.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficiency, in terms of
      decreasing overall mortality (primary endpoint), of an immunoglobulin M (IgM)
      enriched, polyclonal intravenous immunoglobulin preparation (IVIg) (Pentaglobin;
      Biotest AG, Dreieich, Germany) in the treatment of a group of patients affected
      by sepsis after cardiac surgery. A secondary endpoint was to evaluate which
      subgroup, on the basis of the infectious state when the patient enrolled, could
      benefit the most from the treatment. Another secondary endpoint was the
      evaluation of an improvement in the severity score or in other variables such as
      Glasgow Coma Scale; arterial pressure (systolic, average, and diastolic); heart
      rate; central venous pressure; cardiac index; respiratory rate; PaO(2), F(I)O(2),
      and the ratio of PaO(2) to F(I)O(2); pH, base excess, and bicarbonate; C reactive
      protein and leukocytes; platelets, prothrombin time, partial thromboplastin time,
      fibrinogen, and anti-thrombin III; creatinine; and bilirubin. DESIGN:
      Retrospective case-controlled study. SETTING: Cardiovascular intensive care unit
      of a university hospital. PARTICIPANTS: Sixty-six patients who developed sepsis
      in the postoperative period after cardiac surgery were admitted to the
      cardiovascular intensive care unit from June 1, 2001, to June 30, 2003: 30
      patients (45.5%) had valvular surgery, 18 (27.5%) had myocardial
      revascularization, 14 (21%) had thoracic aorta surgery, and 4 (6%) had other
      surgery. INTERVENTIONS: From the 66 patients diagnosed with sepsis, 22 patients
      (IVIg group) received IgM-enriched immunoglobulins in addition to the
      conventional therapy, whereas the other 44 patients (control group) were treated
      only with conventional therapy. The decision as to whether or not to administer
      the immunoglobulins was made by physicians in the intensive care unit.
      MEASUREMENTS AND MAIN RESULTS: Of the 66 patients, 8 patients (3 from the IVIg
      group and 5 from the control group) had sepsis, 47 patients (15 from the IVIg
      group and 32 from the control group) had severe sepsis, and 11 patients had
      septic shock (4 from the IVIg group and 7 from the control group). The overall
      mortality rate was 31.8% without significant differences between groups (22.7%
      IVIg group v 36.4% control group, p = not significant). Among the 47 patients
      affected by severe sepsis, those from the control group had a mortality rate
      significantly higher than that of the IVIg group (12/32 [37.5%] v 1/15 [6.6%], p
      = 0.036 [2-sided Fisher exact test]). The 70-day survival rate was significantly
      higher in the IVIg group than in the control group (log-rank test, p < 0.04). No
      significant differences were found between study groups in Acute Physiology and
      Chronic Health Evaluation II or SOFA scores. CONCLUSIONS: The polyclonal IgM
      enriched immunoglobulins did not significantly reduce the mortality rate in the
      overall study population. However, in the subgroup of patients with severe
      sepsis, they improved the survival rate significantly.

PMID- 16085248
TI  - Major clinical outcomes in adults undergoing thoracic aortic surgery requiring
      deep hypothermic circulatory arrest: quantification of organ-based perioperative
      outcome and detection of opportunities for perioperative intervention.
AB  - OBJECTIVE: The purpose of this study was to describe clinical outcome after adult
      thoracic aortic surgery requiring standardized deep hypothermic circulatory
      arrest (DHCA), to determine mortality and length of stay, neurologic outcome,
      cardiorespiratory outcome, and hemostatic and renal outcome after DHCA. DESIGN:
      Retrospective and observational. SETTING: Cardiothoracic operating rooms and
      intensive care unit (ICU). PARTICIPANTS: All adults requiring thoracic aortic
      repair with DHCA. INTERVENTIONS: None. The study was observational. MAIN RESULTS:
      The cohort size was 110. All patients received an antifibrinolytic. The mortality
      rate was 8.2%. The mean length of stay was 6.8 days (ICU) and 14.0 days
      (hospital). The incidence of stroke was 8.1% and postoperative delirium was
      10.9%. The rate of postoperative atrial fibrillation was 43.6%; 19.1% required
      postoperative mechanical ventilation longer than 72 hours. Chest tube drainage
      was 931 mL for the first 24 hours. Postoperative dialysis was required in 1.8% of
      patients. Renal dysfunction occurred in 40% to 50% of patients, depending on the
      definition. CONCLUSIONS: The protocol for DHCA at the authors' institution is
      associated with superior or equivalent perioperative outcomes to those reported
      in the literature. This study identified the need for further quantification of
      the clinical outcomes after DHCA in order to prioritize outcome-based hypothesis
      driven prospective intervention in DHCA.

PMID- 16085249
TI  - Antifibrinolytic use and bleeding during surgery on the descending thoracic
      aorta: a multivariate analysis.
AB  - OBJECTIVES: The purpose of this study was to determine the potential benefit of
      antifibrinolytic (AF) therapy in improving hemostasis in descending aortic
      surgery in which extracorporeal distal perfusion is used. DESIGN: Retrospective
      database study. SETTING: University hospital. PARTICIPANTS: Seventy-two patients
      who underwent descending thoracic or thoracoabdominal aortic replacement during
      the period from January 1993 through December 1996 when the use of AF therapy was
      emerging. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Seventy-two records
      met criteria for inclusion. The use of AF therapy had no significant effect on
      any bleeding or transfusion outcome in any model. Excessive chest tube drainage
      postoperatively was independently associated with repeat surgery and
      intraoperative hypothermia. The risk of receiving a red blood cell (RBC)
      transfusion was independently predicted by low preoperative hemoglobin and age >
      or =65 years. Cross-clamp was an independent predictor of receiving a transfusion
      of non-RBC products (p = 0.03). CONCLUSIONS: The authors could not show a
      beneficial effect of AF therapy on bleeding and transfusion, although current
      practice shows that this therapy continues to be used. Because heterogeneity of
      patient population exists and bias cannot be completely excluded, a prospective
      investigation evaluating efficacy and safety in this population is warranted.

PMID- 16085250
TI  - Effects of hemodilution, blood loss, and consumption on hemostatic factor levels
      during cardiopulmonary bypass.
AB  - OBJECTIVES: The purpose of this study was to determine quantitatively the effects
      of consumption, hemodilution, and blood loss on coagulation and fibrinolytic
      factor levels during cardiopulmonary bypass. DESIGN: A combination of measured
      levels of prothrombin, antithrombin, fibrinogen, plasminogen, and antiplasmin
      along with their activation markers F1.2, thrombin-antithrombin complex,
      fibrinopeptide A, plasmin-antiplasmin complex, and D-dimer were used with a
      computer model of each patient's vascular and hemostatic systems to estimate the
      cardiopulmonary bypass-associated loss of each factor because of hemodilution,
      blood loss, and consumption. SETTING: University hospital. PARTICIPANTS: Nine
      patients undergoing coronary artery bypass graft surgery. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: At baseline, it was estimated that on average 2%,
      3%, and 25%, respectively, of the baseline liver secretion of plasminogen,
      prothrombin,and fibrinogen were consumed by activation of these proteins. During
      cardiopulmonary bypass, thrombin and plasmin generation were increased, whereas
      fibrin generation was decreased because of heparin. Compared with baseline,
      hemodilution during cardiopulmonary bypass resulted in an average 35% +/- 7%
      decrease in the concentration of coagulation and fibrinolytic proteins, whereas
      blood loss was responsible for an average 6% +/- 5% decrease in these proteins.
      Blood loss varied substantially among patients, resulting in <1% to 14% decreases
      in hemostatic protein levels. On average, consumption because of activation
      resulted in less than a 1% drop in the concentration of coagulation and
      fibrinolytic factors during cardiopulmonary bypass. CONCLUSIONS: Hemodilution is
      the primary cause of the drop in coagulation and fibrinolytic proteins during
      routine cardiopulmonary bypass, followed by blood loss, whereas consumption
      accounts for less than a 1% drop in most patients.

PMID- 16085251
TI  - Comparison of lumbar epidural tramadol and lumbar epidural morphine for pain
      relief after thoracotomy: a repeated-dose study.
AB  - OBJECTIVE: The purpose of this study was to compare lumbar epidural morphine and
      lumbar epidural tramadol with respect to onset and duration of analgesia,
      analgesic efficacy, and drug-related side effects after muscle-sparing
      thoracotomy. DESIGN: Prospective, randomized, double-blind, clinical study.
      SETTING: Single university hospital. PARTICIPANTS: Forty patients who underwent
      elective muscle-sparing thoracotomy. INTERVENTIONS: Before anesthesia induction,
      an epidural catheter was placed in the L2-3 or L3-4 interspace using the loss-of
      resistance technique. On arrival at the intensive care unit, patients were
      randomized to receive doses of either 100 mg of tramadol (group T) or 4 mg of
      morphine (group M) via the lumbar epidural catheter. Each dose was diluted in 10
      mL of normal saline. On awakening from anesthesia, if the patient's pain score on
      a 0- to 100-mm visual analog scale was above 40 mm, the initial epidural drug
      dose was administered. The initial injection in each case was taken as time 0.
      Subsequent pain scores above 40 mm were considered indications for epidural
      dosing; each patient was allowed 2 doses in the first 12 hours postoperatively
      and 2 more in the second 12 hours. MEASUREMENTS AND MAIN RESULTS: The groups'
      analgesia onset times were similar, but duration of analgesia was significantly
      shorter in group T than in group M (p < 0.01). There were no differences between
      the groups with respect to pain scores at rest or during coughing at any of the
      time points investigated. Sedation scores were lower in group T than in group M
      at 1, 2, 3, 4, and 8 hours (p value range, 0.0001-0.05). Compared with group T,
      group M showed significantly greater drops in arterial oxygen tension from
      baseline at 3, 4, 8, and 12 hours (p value range, 0.0001-0.05). The group means
      for arterial carbon dioxide tension and respiratory rate were similar at all time
      points investigated. CONCLUSION: The study revealed that the quality of analgesia
      achieved with repeated doses of lumbar epidural tramadol after muscle-sparing
      thoracotomy is comparable to that achieved with repeated doses of lumbar epidural
      morphine. Compared with morphine, lumbar epidural tramadol results in less
      sedation and a less-pronounced decrease in oxygenation.

PMID- 16085252
TI  - Acetaminophen decreases early post-thoracotomy ipsilateral shoulder pain in
      patients with thoracic epidural analgesia: a double-blind placebo-controlled
      study.
AB  - OBJECTIVE: Despite effective epidural analgesia, up to 85% of post-thoracotomy
      patients complain of moderate-to-severe ipsilateral shoulder pain. This study
      assessed the efficacy of acetaminophen in decreasing postoperative shoulder pain
      after a thoracotomy. DESIGN: Double-blind randomized and placebo-controlled
      study. SETTING: University medical center. PARTICIPANTS: 65 patients.
      INTERVENTION: Patients were randomized into 2 groups; 31 patients received
      acetaminophen (group A), and 34 patients received a placebo (group P). After
      induction of anesthesia, patients received either a loading dose of
      acetaminophen, 1000 mg intrarectally, or a placebo suppository. Thereafter,
      acetaminophen, 650 mg, or a placebo, was administered intrarectally every 4 hours
      for 48 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Postoperative pain
      at the surgical site and shoulder pain were assessed separately every 4 hours for
      48 hours using a numerical rating scale (NRS). Rescue analgesia for severe
      shoulder pain (NRS > 7) consisted of subcutaneous hydromorphone. Sixty-three
      patients experienced shoulder pain (97% prevalence). Demographic and
      intraoperative data were similar between the 2 groups. Average NRS for shoulder
      pain was higher in group P compared with group A at 8, 12, and 16 hours
      postoperatively (3.1 +/- 2.9, 2.6 +/- 2.6, 2.3 +/- 2.4 vs 1.8 +/- 2.6, 1.2 +/-
      1.5, 1.3 +/- 1.8; P < 0.05). The total dose of hydromorphone did not differ
      between the 2 groups at 16, 24, and 48 hours. CONCLUSION: Acetaminophen decreases
      post-thoracotomy ipsilateral shoulder pain when given preemptively and regularly
      during the first 48 hours postoperatively in patients who received thoracic
      epidural analgesia.

PMID- 16085253
TI  - Patterns of changes in arterial PO2 during one-lung ventilation: a comparison
      between patients with severe pulmonary emphysema and patients with preserved lung
      function.
AB  - OBJECTIVES: One-lung ventilation (OLV) during thoracoscopic surgery is associated
      with a significant decline in arterial PO(2) in patients with severe pulmonary
      emphysema and patients with preserved lung function. The authors hypothesized
      that patterns of arterial PO(2) changes are different in these 2 patient groups.
      DESIGN: Prospective nonrandomized study. SETTING: University hospital.
      PARTICIPANTS: Twenty-five patients undergoing thoracoscopic interventions: 16
      with severe pulmonary emphysema and 9 patients without emphysema. INTERVENTIONS:
      Continuous arterial blood gas measurement (PaO(2), PaCO(2), pHa) during OLV of
      the left lung in left lateral position using the Paratrend 7 blood gas monitoring
      system (PT7; Pfizer Hospital Products Group, High Wycombe, UK). MAIN RESULTS: The
      decrease of PaO(2) was delayed in patients with severe emphysema. Steady state
      (defined as DeltaPaO(2) <7.5 mmHg/min) was reached after 18 +/- 4 minutes
      compared with 11 +/- 3 minutes (mean +/- standard deviation) in patients with
      normal lung function (p = 0.0002). PaO(2) values at steady state were comparable
      (p = 0.49); the pattern of changes in PaO(2) for the first 15 minutes of left
      sided OLV was significantly different between the groups (p = 0.0004). The
      difference of predicted versus measured PaO(2) at steady state was -48 +/- 160
      mmHg for patients with emphysema and -51 +/- 60 mmHg for patients with normal
      lung function (p = 0.019). CONCLUSION: During OLV, oxygenation is better
      preserved for a longer period of time in patients with severe pulmonary emphysema
      as compared with patients with normal lung function. In contrast to patients
      without emphysema, prediction of oxygenation during OLV for the individual
      patient with emphysema is unreliable because of large interindividual
      differences.

PMID- 16085254
TI  - Monitoring oxygenator expiratory isoflurane concentrations and the bispectral
      index to guide isoflurane requirements during cardiopulmonary bypass.
AB  - OBJECTIVE: The purpose of this study was to measure the changes in isoflurane
      requirements during the rewarming phase of cardiopulmonary bypass with moderate
      hypothermia. DESIGN: An observational study. SETTING: University hospital, single
      center. PARTICIPANTS: Forty patients undergoing elective coronary artery bypass
      surgery with cardiopulmonary bypass. INTERVENTIONS: Isoflurane requirements were
      quantified by measuring the concentrations in the oxygenator expiratory gas.
      Anesthesia was guided by bispectral index monitoring. MEASUREMENTS AND MAIN
      RESULTS: Isoflurane concentrations required to maintain the bispectral index
      between 40 and 50 during the rewarming phase of cardiopulmonary bypass were
      measured. There was a progressive increase in expiratory isoflurane requirements
      during rewarming from 30 degrees C to 37 degrees C, with a Pearson correlation
      coefficient of 0.78. There was a significant difference in the concentration
      required at 30 degrees C (0.41% +/- 0.14%) compared with 37 degrees C (1.00% +/-
      0.12%). CONCLUSION: Isoflurane requirements are reduced during hypothermic
      cardiopulmonary bypass. Monitoring anesthetic concentrations in the oxygenator
      expiratory gas may be a useful adjunct to monitoring the depth of anesthesia.

PMID- 16085255
TI  - Xenon and the inflammatory response to cardiopulmonary bypass in the rat.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of xenon on
      the inflammatory response to cardiopulmonary bypass. DESIGN: Prospective,
      randomized experimental study. SETTING: University research laboratory.
      PARTICIPANTS: Sprague-Dawley rats. INTERVENTIONS: After surgical preparation,
      rats were randomly divided into 4 groups: (1) SHAM rats were cannulated but did
      not undergo cardiopulmonary bypass; (2) cardiopulmonary bypass rats were
      subjected to 60 minutes of cardiopulmonary bypass using an oxygenator receiving a
      30% O(2), 65% N(2), and 5% CO(2) gas mixture; (3) MK801 rats received MK801 (0.15
      mg/kg intravenous) 15 minutes before 60 minutes of cardiopulmonary bypass with
      the same gas mixture; and (4) xenon rats underwent 60 minutes of cardiopulmonary
      bypass receiving a 30% O(2), 60% xenon, 5% N(2), and 5% CO(2) gas mixture.
      MEASUREMENTS AND MAIN RESULTS: All bypass groups showed elevations in both
      cytokines compared with the SHAM-operated group. However, the inflammatory
      response to cardiopulmonary bypass in the group receiving xenon was no different
      from the other bypass groups. CONCLUSIONS: Xenon appears to have no effect on the
      inflammatory response to cardiopulmonary bypass, making its previously described
      neuroprotective effect during cardiopulmonary bypass likely independent of any
      inflammation modulation.

PMID- 16085256
TI  - Patients with positive preoperative stress tests undergoing vascular surgery.
AB  - OBJECTIVE: To examine the perioperative cardiac morbidity and mortality in
      patients undergoing major vascular surgery with beta-blockade after a positive
      stress test or cardiac catheterization. DESIGN: Retrospective review of a quality
      assurance database. SETTING: A university teaching hospital. PARTICIPANTS: A
      consecutive series of 31 patients undergoing peripheral vascular or aortic
      surgery after a positive stress test or catheterization between November 2001 and
      September 2003. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: All 31
      patients had a preoperative positive stress test and/or cardiac catheterization,
      with 12 having multiple areas at risk for myocardial ischemia. None had an
      intervening coronary revascularization. Twenty-seven had at least one of the
      intermediate clinical predictors as defined by the American College of Cardiology
      and 7 had a left ventricular ejection fraction < 40%. Twenty-three patients had
      been on a beta-blocker and continued on it, while the remainder started on it de
      novo perioperatively. None of the patients suffered from myocardial infarction,
      congestive heart failure, or cardiac death perioperatively. CONCLUSIONS: This
      case series reports on the authors' experience with patients undergoing high-risk
      vascular surgery after a positive stress test or catheterization, but without an
      intervening coronary intervention. All patients received perioperative beta
      blockade and had a very low adverse cardiac event rate. With reduction of adverse
      events by beta-blockade, the likelihood of a positive event may be reduced and
      the utility of the test in risk stratification may be questioned.

PMID- 16085257
TI  - Normothermic cardiopulmonary bypass in a patient with moyamoya disease.

PMID- 16085258
TI  - Cardiopulmonary bypass support for percutaneous coronary interventions: what the
      anesthesiologist needs to know.

PMID- 16085259
TI  - Sepsis from insidious pacemaker infection and unsuspected tricuspid valve
      endocarditis: the importance of transesophageal echocardiography in guiding
      explantation strategy.

PMID- 16085260
TI  - Infected atrial myxoma presenting with septic shock.

PMID- 16085261
TI  - Tension hydrothorax: a near-fatal complication of central venous catheterization.

PMID- 16085262
TI  - Intraoperative diagnosis of a ruptured intra-aortic balloon in a child undergoing
      thoracic surgery.

PMID- 16085263
TI  - The utility of dobutamine stress echocardiography for perioperative and long-term
      cardiac risk assessment.

PMID- 16085264
TI  - Case 4--2005. Utility of transesophageal echocardiography in the diagnosis of a
      previously undetected atrial septal aneurysm with shunt.

PMID- 16085265
TI  - Pro: Carotid angioplasty and stenting will be the first-line interventional
      therapy for stroke prevention in patients with extracranial carotid occlusive
      disease.

PMID- 16085266
TI  - Con: Carotid endarterectomy is the present and future gold standard for stroke
      prevention.

PMID- 16085267
TI  - Intraoperative oxygen desaturation and electrocardiographic changes in a patient
      with Hanhart syndrome.

PMID- 16085268
TI  - What happened during the insertion of a superior vena cava cannula and pulmonary
      artery catheter for minimally invasive robot-assisted cardiac surgery?

PMID- 16085269
TI  - An infrequent case of fire in the operating room during open surgery of a
      tracheobronchopleural fistula.

PMID- 16085270
TI  - Spontaneous contralateral pneumothorax: an unusual cause of respiratory distress
      after pneumonectomy.

PMID- 16085271
TI  - Why blue blushed.

PMID- 16085272
TI  - A modified landmark-guided technique for cannulation of the internal jugular vein
      in pediatric patients: a preliminary report.

PMID- 16085273
TI  - One-lung isolation using a double-balloon blocker technique.

PMID- 16085274
TI  - Allium cepa derived EROD as a potential biomarker for the presence of certain
      pesticides in water.
AB  - Allium cepa root length inhibition test is a well recommended bioassay for the
      evaluation of the toxicity of various polluted waters. The utility of EROD (7
      ethoxy resorufin O-deethylase) as a potential biomarker of pesticide pollution
      was investigated using the Allium cepa system. Onion bulbs exposed to model water
      samples containing any of the six pesticides viz. 2,4-D, HCB, malathion,
      carbaryl, DDT and endosulphan were analyzed for EROD activity. The pesticide
      treatment resulted in the enhanced activity of the enzyme, with carbaryl and HCB
      causing 63- and 53-fold induction respectively with respect to the control at a
      dose of 1.2 ppb. The industrial wastewater samples from Ghaziabad city of
      Northern India resulted in about a 68-fold rise in the EROD activity, whereas the
      Aligarh samples did not exhibit any change within the statistical limit. These
      results suggest the presence of the test pesticides in the Ghaziabad sample and
      their absence in the Aligarh sample. Pesticide analysis in the test water samples
      by HPLC supported this to a large extent. Presence of cycloheximide in the test
      system brought down the EROD activity, equal to that of control, suggesting the
      de novo synthesis of the enzyme following the exposure of Allium cepa to
      pesticides. These studies suggest that the Allium cepa derived EROD can act as a
      potential biomarker of certain pesticides since even 1ppb of total/individual
      pesticides brought about >10-fold induction of EROD. We recommend the assay of
      EROD in the Allium cepa system as a presumptive test for the detection of these
      pesticides before using analytical techniques like HPLC.

PMID- 16085275
TI  - Ammonia emissions from the composting of different organic wastes. Dependency on
      process temperature.
AB  - Ammonia emissions were quantified for the laboratory-scale composting of three
      typical organic wastes with medium nitrogen content: organic fraction of
      municipal solid wastes, raw sludge and anaerobically digested sludge; and the
      composting of two wastes with high nitrogen content: animal by-products from
      slaughterhouses and partially hydrolysed hair from the leather industry. All the
      wastes were mixed with the proper amount of bulking agent. Ammonia emitted in the
      composting of the five wastes investigated revealed a strong dependence on
      temperature, with a distinct pattern found in ammonia emissions for each waste in
      the thermophilic first stage of composting (exponential increase of ammonia
      emitted when increasing temperature) than that of the mesophilic final stage
      (linear increase of ammonia emissions when increasing temperature). As composting
      needs high temperatures to ensure the sanitisation of compost and ammonia
      emissions are one of the main environmental impacts associated to composting and
      responsible for obtaining compost with a low agronomical quality, it is proposed
      that sanitisation is conducted after the first stage in large-scale composting
      facilities by a proper temperature control. CAPSULE: Ammonia emission pattern and
      correlation with process temperature are presented for the composting process of
      different organic wastes.

PMID- 16085276
TI  - New evidences for old biomarkers: effects of several xenobiotics on EROD and AChE
      activities in Zebra mussel (Dreissena polymorpha).
AB  - The biomarker approach is widely used both in vertebrates and invertebrates for
      environmental biomonitoring, because it can supply an integrated response for
      multi-xenobiotics contamination. However, the use of biomarkers requires the
      identification of every possible variation that can influence the biochemical
      response, because ecosystems are generally subject to a mixture of pollutants,
      which can create additive, opposite or competitive effects. In recent years,
      there has been considerable interest in the use of biomarkers within marine
      bivalves, while very few data are available for freshwater molluscs. The aim of
      this research was to investigate changes on EROD and AChE activities in the
      freshwater bivalve Zebra mussel (Dreissena polymorpha) exposed to different
      pollutants (Arochlor 1260, CB 153 and 126, pp'DDT, chlorpyrifos, carbaryl) at
      laboratory conditions, in order to standardize the analytical procedures and to
      highlight eventual interferences on enzyme activities. Chemical concentrations in
      the mussel soft tissues were analyzed by GC/MS-MS. Main results showed a
      significant induction of EROD activity when mussels were exposed to 100 ng/l of
      PCB mixture of Arochlor 1260 and dioxin-like CB 126, but this congener showed
      also a clear competitive inhibition after 48 h of exposure. Surprisingly, pp'DDT
      determined a significant decrease of basal EROD activity after only 24 h of
      exposure, even if it was not possible to discriminate between the effect of the
      parent compound and that of its metabolites (DDD, DDE). We also found an
      interaction between the organophosphate insecticide chlorpyrifos, which does not
      directly decrease the AChE activity, and terbutilazine. This herbicide increased
      the biotransformation of the organophosphate compound to its oxidized metabolite
      (oxon), a much stronger AChE inhibitor. The possible use of the oxime Pyridine-2
      Aldoxime Methochloride (2-PAM) to bring back the catalytic activity to basal
      levels was also demonstrated.

PMID- 16085277
TI  - Copper and zinc induction of lipid peroxidation and effects on antioxidant enzyme
      activities in the microalga Pavlova viridis (Prymnesiophyceae).
AB  - The metal-induced lipid peroxidation and response of antioxidative enzymes have
      been investigated in the marine microalga Pavlova viridis to understand the
      mechanisms of metal resistance in algal cells. We have analyzed superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) activities and
      glutathione (GSH) contents in microalgal cells grown at different concentrations
      of copper and zinc. In response to each metal, lipid peroxidation was enhanced
      with the increase of concentrations, as an indication of the oxidative damage
      caused by metal concentration assayed in the microalgae cells. Exposure of P.
      viridis to the two metals caused changes in enzyme activities in a different
      manner, depending on the metal assayed: after copper treatments, total SOD
      activity was enhanced, while it was reduced after zinc exposure. Copper and zinc
      stimulated the activities of CAT and GSH whereas GPX showed a remarkable increase
      in activity in response to copper treatments and decrease after zinc treatments.
      These results suggest that an activation of some antioxidant enzymes was enhanced
      to counteract the oxidative stress induced by the two metals.

PMID- 16085278
TI  - A 3D quantitative comparison of trapezium and trapezoid relative articular and
      nonarticular surface areas in modern humans and great apes.
AB  - The structure and functions of the modern human hand are critical components of
      what distinguishes Homo sapiens from the great apes (Gorilla, Pan, and Pongo). In
      this study, attention is focused on the trapezium and trapezoid, the two most
      lateral bones of the distal carpal row, in the four extant hominid genera,
      representing the first time they have been quantified and analyzed together as a
      morphological-functional complex. Our objective is to quantify the relative
      articular and nonarticular surface areas of these two bones and to test whether
      modern humans exhibit significant shape differences from the great apes, as
      predicted by previous qualitative analyses and the functional demands of
      differing manipulative and locomotor strategies. Modern humans were predicted to
      show larger relative first metacarpal and scaphoid surfaces on the trapezium
      because of the regular recruitment of the thumb during manipulative behaviors;
      alternatively, great apes were predicted to show larger relative second
      metacarpal and scaphoid surfaces on the trapezoid because of the functional
      demands on the hands during locomotor behaviors. Modern humans were also expected
      to exhibit larger relative mutual joint surfaces between the trapezoid and
      adjacent carpals than do the great apes because of assumed transverse loads
      generated by the functional demands of the modern human power grip. Using 3D bone
      models acquired through laser digitizing, the relative articular and nonarticular
      areas on each bone are quantified and compared. Multivariate analyses of these
      data clearly distinguish modern humans from the great apes. In total, the
      observed differences between modern humans and the great apes support
      morphological predictions based on the fact that this region of the human wrist
      is no longer involved in weight-bearing during locomotor behavior and is instead
      recruited solely for manipulative behaviors. The results provide the beginnings
      of a 3D comparative standard against which further extant and fossil primate
      wrist bones can be compared within the contexts of manipulative and locomotor
      behaviors.

PMID- 16085279
TI  - The rise of the hominids as an adaptive shift in fallback foods: plant
      underground storage organs (USOs) and australopith origins.
AB  - We propose that a key change in the evolution of hominids from the last common
      ancestor shared with chimpanzees was the substitution of plant underground
      storage organs (USOs) for herbaceous vegetation as fallback foods. Four kinds of
      evidence support this hypothesis: (1) dental and masticatory adaptations of
      hominids in comparison with the African apes; (2) changes in australopith
      dentition in the fossil record; (3) paleoecological evidence for the expansion of
      USO-rich habitats in the late Miocene; and (4) the co-occurrence of hominid
      fossils with root-eating rodents. We suggest that some of the patterning in the
      early hominid fossil record, such as the existence of gracile and robust
      australopiths, may be understood in reference to this adaptive shift in the use
      of fallback foods. Our hypothesis implicates fallback foods as a critical
      limiting factor with far-reaching evolutionary effects. This complements the more
      common focus on adaptations to preferred foods, such as fruit and meat, in
      hominid evolution.

PMID- 16085280
TI  - PCBs in sediments and the coastal food web near a local contaminant source in
      Saglek Bay, Labrador.
AB  - Polychlorinated biphenyls (PCBs) were measured in marine sediments and the
      coastal food web in Saglek Bay, Labrador, to investigate the influence of a local
      PCB source. Saglek Bay has been the site of a military radar station since the
      late 1950s and there was PCB-contaminated soil at a beach prior to cleanup in
      1997-1999. PCB concentrations in marine sediments during 1997-1999 ranged from
      0.24 to 62000 ng/g (dry weight) and decreased exponentially with distance from
      the contaminated beach. Given this gradient, spatial trends of PCBs in the food
      web were examined over four zones, according to distance from the contaminated
      beach: within 1.5 km--zone one, 1.5-4.5 km--zone two, 4.5-7.5 km--zone three, and
      greater than 7.5 km--zone four. PCB concentrations in a bottom-feeding fish
      (shorthorn sculpin, Myoxocephalus scorpius), decreased significantly from zone
      one to zone two, three, four, and distant Labrador reference sites. PCB
      concentrations in the eggs of a diving seabird (black guillemot, Cepphus grylle)
      were as high as 48000 ng/g during 1997-1999 and average concentrations in zones
      one and two were 84 and 13 times higher than in zone four. Marine invertebrates
      closely reflected the concentrations of PCBs in the associated sediment. In
      contrast to the benthic-based food web, anadromous arctic char (Salvelinus
      alpinus) showed no evidence of PCB accumulation from the contaminated sediments.
      Relatively high PCB concentrations were discovered in some great black-backed
      gulls (Larus marinus) and ringed seals (Phoca hispida) but appear to relate more
      to their high trophic level than sampling location. Those species that fed on or
      near the seabed and had limited foraging ranges were strongly influenced by the
      local contamination. Total PCB concentrations in the benthic-based food web were
      significantly higher than background levels for a distance of at least 7.5 km
      from the contaminated beach. This area is small in the context of widely
      distributed contamination from long-range transport but the area's high
      concentrations are comparable to levels associated with adverse effects
      elsewhere. Our findings should be useful to better assess the environmental
      impacts of PCB contamination at other coastal sites in the Arctic.

PMID- 16085282
TI  - Changes associated with the aging face.
AB  - The demand for facial plastic surgery has increased dramatically in recent years
      as persons from all socioeconomic levels and age groups have become interested in
      facial rejuvenation. As the population ages, the demand for esthetic surgery in
      the elderly will increase at an even greater rate. Before the surgeon begins to
      learn specific techniques in facial plastic surgery, he or she should have a
      thorough understanding of the anatomy of the aging face. Safe and effective
      esthetic surgery is possible only when the anatomic changes associated with the
      aging face are appreciated by the surgeon and patient.

PMID- 16085283
TI  - Patient selection for aging face surgery.
AB  - All surgeons have their individual style and approach to patient selection;
      however, some fundamental principles are helpful in guiding this process. This
      discussion outlines some of the principles that the author has found helpful in
      approaching the aging face consultation.

PMID- 16085284
TI  - Evolution of rhytidectomy techniques.
AB  - Rhytidectomy techniques have advanced greatly since their inception a century
      ago. Today, a rich array of procedures is available, ranging from limited and
      minimally invasive approaches to extensive dissections. The evolution of
      rhytidectomy is outlined herein, along with a review of the relative indications
      and advantages of commonly practiced procedures.

PMID- 16085285
TI  - Experience with percutaneous suspension of the malar fat pad for midface
      rejuvenation.
AB  - Repositioning of the ptotic malar fat pad represents a key element of midface
      rejuvenation. Traditional face-lifting techniques have been minimally effective
      in correcting the midface changes commonly seen in aging. Many candidates,
      especially younger patients, desire procedures that have rapid recovery times
      with reduced risk and the absence of visible incisions. Percutaneous suspension
      of the malar fat pad to reposition it in a more youthful position is a minimally
      invasive technique producing a long lasting elevation that would be a welcomed
      addition to midface rejuvenation.

PMID- 16085286
TI  - Pitfalls of midface surgery.
AB  - The endoscopic forehead midface lift is perhaps the most powerful tool has been
      made available to the facial aesthetic surgeon in the last 10 years. Although
      this technique can reap the greatest rewards, it is also fraught with the
      greatest peril. A difficult dissection, prolonged period of edema, and numerous
      other pitfalls have tempered enthusiasm among facial aesthetic surgeons for this
      powerful technique. Nonetheless, the midface lift can be performed both safely
      and effectively. Through careful analysis of the pitfalls of midface surgery, one
      can adopt principles that help prevent or minimize potential complications. Such
      an approach can maximize the surgical benefit to the patient and lessen the
      anxiety surrounding the procedure for the patient and surgeon alike.

PMID- 16085287
TI  - The extended minimal incision approach to midface rejuvenation.
AB  - Recent major advancements in comprehensive facial rejuvenation have focused on
      management of midfacial aging. Multiple techniques have been described to treat
      the aging midface; the mere nature of so many approaches is evidence that no one
      technique has prevailed. Although the nasolabial region remains a challenge to
      correct, the approach described herein provides comprehensive rejuvenation of the
      midface, lateral brow, and jawline. The technique is performed via a minimal
      incision brow-lift approach and has been performed (with minor modifications) by
      the senior author in more than 650 patients over the past 9 years. The technique
      has proven to be safe, reliable, and effective.

PMID- 16085288
TI  - SMAS facelift techniques to minimize stigmata of surgery.
AB  - Patients seeking facial rejuvenation surgery are commonly concerned about their
      postoperative appearance. Their anxiety is expressed in the form of general
      statements about looking too different, not themselves, or being recognized for
      having had "something done." Typically, these reservations are the result of
      scars or deformities seen in a public figure, relative, or passerby. The more
      recognizable stigmata of facial rejuvenation surgery include unnatural hairlines,
      tragal distortions, ear lobule deformities, irregular neck contours, and an
      overall look of being lifted. The specific techniques and philosophy to prevent
      these stigmata are presented herein in a problem-specific format.

PMID- 16085289
TI  - Deep plane face-lift.
AB  - The deep plane face-lift is a safe and reliable technique for treatment of the
      aging face. It affords improvement in the lower face and midface. The use of
      fibrin glue in the face-lift has improved the healing and recovery of patients.

PMID- 16085290
TI  - Male face-lift.
AB  - Middle-aged men represent an emerging group expressing an interest in facial
      rejuvenation procedures. One must understand the complex differences in
      motivation, psychosocial factors, and aspects associated with anatomy and facial
      aging that are unique to men. To maximize postoperative results and increase
      patient satisfaction, the facial plastic surgeon must adjust perioperative
      management and surgical techniques when performing a male face-lift.

PMID- 16085291
TI  - Submentoplasty.
AB  - Aging changes to the anterior neck can produce skin laxity, accumulation of
      submental fat, platysmal banding, and ptosis of the underlying neck structures.
      To rejuvenate the cervicomental region, the surgeon must accurately diagnose the
      anatomic irregularities and make appropriate recommendations for surgical
      correction. Because there are wide variations of anterior neck anatomy among
      individuals, it is necessary to "customize" the surgery in this area for each
      patient by employing single isolated procedures or multiple techniques. A
      stepwise approach in the management of the submentum can facilitate this goal and
      guide the surgeon in selecting the appropriate procedures for each individual.

PMID- 16085292
TI  - Complications of rhytidectomy.
AB  - Complications after rhytidectomy can be distressing for the patient and surgeon.
      Although meticulous surgical technique and a complete understanding of the causes
      of adverse outcomes can minimize the risk for severe complications, an open and
      honest rapport with the patient when complications do occur is essential for
      effective management. This article discusses the likely etiologies of face-lift
      complications, techniques to prevent them, and helpful treatments when
      complications occur.

PMID- 16085293
TI  - Placental site trophoblastic tumour: clinical features and management.
AB  - OBJECTIVE: To describe the clinical features, treatment and outcome of all
      consecutive patients with placental site trophoblastic tumour (PSTT) treated at
      the Sheffield Trophoblast Centre and to compare these findings to other reports.
      METHOD: All cases of PSTT on the Sheffield Trophoblastic Tumour Centre database
      from 1984 to 2004 were reviewed. Data obtained included age at diagnosis,
      antecedent pregnancy (AP), interval from antecedent pregnancy until diagnosis,
      presenting features, presenting serum human chorionic gonadotrophin hormone (hCG)
      level, number and sites of metastases, treatment received, outcome and follow-up.
      RESULTS: Seventeen patients with PSTT were identified from the database which
      incorporates a total of 7489 cases of trophoblastic disease. Fourteen (70.6%)
      were more than 30 years old at presentation; 5 were over 40. The median interval
      from pregnancy to diagnosis was 18 months (range 6 months to 22 years). The
      outcome of antecedent pregnancy was a female in 11 out of the 13 patients where
      the sex was known. Eleven (70.6%) of patients presented with irregular vaginal
      bleeding, with or without a preceding period of amenorrhoea. All 8 patients with
      non-metastatic (Stage I) disease were alive and well after hysterectomy (6),
      chemotherapy alone (1) or hysterectomy and chemotherapy (1) whereas only 4 of 9
      patients with metastatic (Stage III/IV) disease were alive and well after
      treatment with chemotherapy and hysterectomy. CONCLUSION: PSTT is rare and
      accounts for 0.23% cases of gestational trophoblastic disease referred to this
      centre. It has a variety of presenting features and its course is unpredictable.
      Metastatic involvement and antecedent pregnancy interval greater than 4 years are
      poor prognostic factors. Hysterectomy is the primary mode of treatment in the
      majority of cases. However, chemotherapy can still play a major role when
      curative surgery is not feasible.

PMID- 16085294
TI  - The curative effect of a second curettage in persistent trophoblastic disease: a
      retrospective cohort survey.
AB  - OBJECTIVE: To assess the curative effect of a second curettage in patients with
      low-risk Persistent Trophoblastic Disease (PTD) after molar pregnancy. METHODS: A
      retrospective cohort survey was performed on 2122 patients registered with the
      Dutch Central Registry for Hydatidiform Moles between 1987 and 2003. Of these,
      422 patients developed PTD. For various reasons, 128 patients were excluded. The
      study group comprised 85 patients with, according to the Dutch guidelines, low
      risk PTD who underwent a second therapeutic curettage as a part of the treatment
      for PTD. The control group consisted of 209 patients with low-risk PTD who did
      not undergo a second curettage. Patients in the study and control group were
      classified for high/low-risk PTD according to the internationally accepted FIGO
      2000 guidelines. Primary outcome measures were the need for chemotherapy and if
      applicable, the number of chemotherapy courses. RESULTS: After second curettage,
      eight out of 85 patients (9.4%) did not need additional chemotherapy which
      significantly differs from the 209 patients in the control group who all needed
      chemotherapy (P < 0.001). A debulking effect of the second curettage was
      observed: a median of 6 courses (interquartile range 3 courses) in the control
      group versus 5 courses (interquartile range 3 courses) in the study group (P =
      0.036). Four out of the 85 (4.8%) patients with a second curettage had a major
      complication (uterine perforation or hemorrhage), which was managed
      conservatively. CONCLUSION: A second curettage cured 9.4% of patients with PTD in
      this historical cohort and reduces the number of courses of chemotherapy. A
      second curettage seems to benefit only a limited number of patients with PTD. A
      randomized controlled prospective trial is needed to confirm this observation.

PMID- 16085295
TI  - Prevention of adhesion formation after radical oophorectomy using a sodium
      hyaluronate-carboxymethylcellulose (HA-CMC) barrier.
AB  - OBJECTIVES: To evaluate the efficacy of a hyaluronate-carboxymethylcellulose (HA
      CMC) barrier for prevention of pelvic adhesion formation in women undergoing
      primary cytoreductive surgery with radical oophorectomy for locally advanced
      epithelial cancer. METHODS: Between 3/1/01 and 3/1/02, all patients undergoing
      primary surgery for locally advanced FIGO Stage III-IV epithelial ovarian cancer
      were prospectively offered study enrollment. Radical oophorectomy (en bloc
      rectosigmoid colectomy) with total pelvic peritonectomy was performed as
      clinically indicated. Intestinal continuity was reestablished via stapled
      anastomosis following complete cytoreduction of pelvic disease. The entire pelvic
      peritoneal defect was covered with subdivided sheets of HA-CMC (6.5 cm x 5.0 cm)
      using a 'quilting' technique. The abdominal wall incision site was not treated
      with adhesion preventive measures. At second-look surgery, four-quadrant pelvic
      (treated area) and abdominal wall (untreated internal control) adhesion scores
      were assigned using a previously validated scoring system. Statistical analysis
      for differences in mean pelvic and abdominal wall adhesion scores was performed
      using Student's t test. RESULTS: Fourteen patients satisfied all inclusion
      criteria. Abdominal wall adhesions were noted in 92.9% of patients. In the
      pelvis, the dorsal peritoneal surfaces were the most common sites of adhesion
      formation (42.9%). Overall, the mean pelvic (treated) adhesion score was
      statistically significantly lower (0.91, SD +/- 1.04) than the mean abdominal
      wall (untreated control) score (5.56, SD +/- 4.55, P = 0.02). There were no
      instances of intestinal anastomotic leak, and no peri-operative complications
      directly attributable to HA-CMC were observed. CONCLUSIONS: Placement of a HA-CMC
      barrier is associated with a significant reduction in the extent and density of
      pelvic adhesion formation following radical oophorectomy and pelvic peritonectomy
      for locally advanced epithelial ovarian cancer.

PMID- 16085296
TI  - Estrogen-priming can enhance progesterone's anti-seizure effects in part by
      increasing hippocampal levels of allopregnanolone.
AB  - Estrogen can be proconvulsant, while progesterone and its metabolite
      allopregnanolone typically have anti-seizure effects. We investigated whether
      estrogen-priming also has anti-seizure effects by altering progesterone's
      metabolism to allopregnanolone, or levels of brain-derived neurotrophic factor
      (BDNF), in the hippocampus. Two experiments investigated effects of different
      estrogen-priming regimen (Experiment 1--10 microg; Experiment 2--2 microg) on
      pentylenetetrazole (PTZ)-induced seizures and levels of estrogen, progesterone
      and allopregnanolone in plasma and hippocampus. In Experiment 1, ovariectomized
      (ovx) rats were administered sesame oil vehicle or 10 microg 17beta-estrogen at
      hour 0. Forty-four hours later, progesterone (500 microg; s.c.) or vehicle was
      administered. At hour 47, PTZ (70 mg/kg i.p.) was administered. For Experiment 2,
      a similar protocol was used except that ovx rats were administered vehicle or 2
      microg 17beta-estradiol at hours 0 and 24. Progesterone, alone or in conjunction
      with either 10 or 2 microg estrogen-priming, tended to increase the latency to,
      and significantly reduced the number of, tonic seizures and elevated levels of
      progestins in hippocampus and plasma. Two, but not 10, micrograms of estrogen
      alone had anti-seizure effects and increased levels of allopregnanolone in the
      hippocampus. BDNF levels in the hippocampus were increased by estrogen-priming,
      but reduced by progesterone administration. Thus, estrogen may have anti-seizure
      effects by enhancing formation of allopregnanolone.

PMID- 16085297
TI  - Fertility after deep intra-uterine artificial insemination of concentrated low
      volume boar semen doses.
AB  - Boar semen can be successfully frozen - highly packed - in small containers
      (medium-straw, MS or MiniFlatPack, MFP). The use of deep intra-uterine artificial
      insemination (DIU-AI) can make possible the deposition of small volumes of this
      thawed, non re-extended semen deeply intra-uterine, close to the sperm reservoir.
      The present experiments studied the fertility achieved after single or double DIU
      AI per oestrus, with special attention to the interval between AI and spontaneous
      ovulation. Semen from two boars of proven fertility was frozen in MS or MFP
      holding 1 x 10(9) total spermatozoa. Multiparous (2-5 parity, n=42) crossbred
      sows were checked for oestrous behaviour after weaning and the occurrence of
      spontaneous ovulation was checked with transrectal ultrasonography (TUS) to
      establish the mean interval between onset of oestrus (OO) and ovulation which was
      found to be when approximately 2/3 of the oestrus period has passed. The sows
      were, in the following standing oestrus, subjected to DIU-AI using thawed semen
      from either MS (n=20) or MFP (n=22), inseminated without further re-extension.
      The sows were randomly allotted to one of three groups: (1) single DIU-AI 8 h
      before expected ovulation (control group, n=19); (2) single DIU-AI 4 h before
      expected ovulation (treatment group S, n=15); and (3) double DIU-AI 12 and 4 h
      before expected ovulation (treatment group D, n=8). Occurrence of spontaneous
      ovulation was confirmed by TUS, performed as during the first oestrous period and
      used to determine the real interval of DIU-AI and ovulation. Pregnancy was also
      confirmed by TUS 28 days after OO in those sows not returning to oestrus. These
      sows were slaughtered (30-45 days of pregnancy), and the appearance of the
      reproductive tract and ovaries, the number of live and dead foetuses, of
      implantation sites and of corpora lutea (CL) were recorded. Sows (n=9) returning
      to oestrus ("open") were re-inseminated (either once [n=4] or twice [n=5]) the
      following oestrus with either MFP (n=5) or MS (n=4) and slaughtered 12-14 h post
      ovulation for recovery of tubal oocytes and of spermatozoa from the uterotubal
      junctions (sperm reservoir), to assess the degree of effectiveness of sperm
      transport. Post-thaw sperm motility was 44.3+/-3.21% in MFP and 42.8+/-0.72% for
      MS (LSmean+/-S.E.M., n.s.), and did not significantly change from thawing to AI.
      The DIU-AI could be performed in all sows, but insertion was difficult (slow >5
      min) in 5/42 sows. Four of these sows returned to oestrus. Pregnancy rate
      averaged 35% (group D: 25%, group S: 40%, control: 36%, n.s.). The interval
      between DIU-AIs and spontaneous ovulation varied largely, ranging from -13 to -3
      h for group C, for group S from -11 to +3 h and for group D from -17 to -4 h.
      Pregnancy rates were clearly related to the interval DIU-AI and ovulation, being
      highest (60%, 12/20) when AI occurred between 8 and 4 h before spontaneous (not
      expected) ovulation. The number of implantation sites ranged 6-22 (n.s. among
      groups), and the number of alive foetuses 2-11 (n.s. among groups). Implantation
      rate (total number of implantations/CL) ranged 48.0-69.7% being highest in the D
      group (P<0.05). The examination of the "open" sows slaughtered 12-14 h post
      ovulation revealed few recovered oocytes were fertilized (approximately 10%).
      Only 40% of oocytes had spermatozoa bound to the zona pellucida, not more than
      two spermatozoa per oocyte. Moreover, low sperm numbers (approximately 4000) were
      found in the sperm reservoirs (UTJs), irrespective of using single or double DIU
      AI (n.s.). The highest values (P<0.05) for these variables were recorded when DIU
      AI (either single or double [second AI]) occurred 4-8 h before ovulation,
      especially when MFP-semen was used (P<0.05). IN CONCLUSION: (1) DIU-AI can be
      easily performed in most sows; (2) pregnancies can be obtained by the DIU-AI of
      low volumes of highly concentrated frozen-thawed boar semen, once or twice during
      oestrus, but fertility is still low, probably owing to an unsatisfactory sperm
      transport when expected and real ovulation differ; and (3) fertility is related
      to the interval DIU-AI and ovulation which should be -8 to -4 h of spontaneous
      ovulation and to the package, MFP having shown better results in vivo. The
      results stress the need for careful, and frequent, control of oestrus signs.

PMID- 16085298
TI  - Relationship between heat stress during the peri-implantation period and early
      fetal loss in dairy cattle.
AB  - The aim of the present study was to establish whether temperature-humidity index
      values, as a measure of heat comfort, from Days 1 to 40 of gestation could be
      associated with the pregnancy loss rate in high producing dairy cows. Data from
      1391 pregnancies were recorded. Pregnancy was diagnosed by transrectal
      ultrasonography between Days 34 and 45, and again 90 days after insemination.
      Pregnancy loss was assumed when the second pregnancy diagnosis on Day 90 proved
      negative and was registered in 7.8% (108/1391) of pregnancies. Mean and maximum
      temperature-humidity index values were established for each cow for Days 0 (day
      of insemination), 1, 2 and 3 after insemination, and averages established for
      Days 0-3, 0-10, 11-20, 21-30 and 31-40 after insemination. Cow and management
      variables previously found to be significantly correlated with the early fetal
      loss in the same geographical area were also recorded. The relative contribution
      of each factor to the probability of pregnancy loss was determined using logistic
      regression models. Based on the odds ratio, a strong association with pregnancy
      loss of the factors warm period of pregnancy (warm period-May to September versus
      cool-October to April), twin pregnancy (as negative factors: odds ratios 3.1 and
      3.4, respectively) and an additional corpus luteum (as a positive factor: odds
      ratio 0.32) was confirmed. The likelihood of pregnancy loss increased by a factor
      of 1.05 for each additional unit of the mean maximum temperature-humidity index
      from Days 21 to 30 of gestation. Logistic regression analysis revealed no
      significant effects of temperature-humidity index values for the remaining
      gestation periods. Our results indicate that heat stress can compromise the
      success of gestation during the peri-implantation period, such that high
      temperature-humidity index values for the period 21-30 days of gestation are a
      risk factor for subsequent early fetal loss.

PMID- 16085299
TI  - From intersubject variability in clinical syndromes to anatomical variability.

PMID- 16085300
TI  - Reference assignment: using language breakdown to choose between theoretical
      approaches.
AB  - We report results of an experimental study with Dutch agrammatic aphasics that
      investigated their ability to interpret pronominal elements in transitive clauses
      and Exceptional Case Marking constructions (ECM). Using the obtained experimental
      results as a tool, we distinguish between three competing linguistic theories
      that aim at determining principles responsible for pronoun distribution:
      Government and Binding (Chomsky, 1981), Reflexivity (Reinhart & Reuland, 1993),
      and Primitives of Binding (Reuland, 2001). The obtained results are inconsistent
      with Government and Binding, but consistent with the latter two theories. We
      further show that the Primitives of Binding framework most naturally explains our
      results. Our proposal is based on the different performance demonstrated by
      patients in transitive clauses and ECM constructions, in combination with the
      often-made claim in the literature regarding the limitation of processing
      resources in this population (e.g., Haarmann and Kolk, 1991, Haarmann and Kolk,
      1994 and Zurif et al., 1993, among others).

PMID- 16085301
TI  - Factors involved in the development of polymerization shrinkage stress in resin
      composites: a systematic review.
AB  - OBJECTIVES: Polymerization shrinkage stress of resin-composite materials may have
      a negative impact on the clinical performance of bonded restorations. The purpose
      of this systematic review is to discuss the primary factors involved with
      polymerization shrinkage stress development. DATA: According to the current
      literature, polymerization stress of resin composites is determined by their
      volumetric shrinkage, viscoelastic behavior and by restrictions imposed to
      polymerization shrinkage. Therefore, the material's composition, its degree of
      conversion and reaction kinetics become aspects of interest, together with the
      confinement and compliance of the cavity preparation. SOURCES: Information
      provided in this review was based on original scientific research published in
      Dental, Chemistry and Biomaterials journals. Textbooks on Chemistry and Dental
      Materials were also referenced for basic concepts. CONCLUSIONS: Shrinkage stress
      development must be considered a multi-factorial phenomenon. Therefore, accessing
      the specific contribution of volumetric shrinkage, viscoelastic behavior,
      reaction kinetics and local conditions on stress magnitude seems impractical.
      Some of the restorative techniques aiming at stress reduction have limited
      applicability, because their efficiency varies depending upon the materials
      employed. Due to an intense research activity over the years, the understanding
      of this matter has increased remarkably, leading to the development of new
      restorative techniques and materials that may help minimize this problem.

PMID- 16085302
TI  - Microtensile bond strength of different components of core veneered all-ceramic
      restorations.
AB  - OBJECTIVES: The present study aims to evaluate the core-veneer bond strength and
      the cohesive strength of the components of three commercial layered all-ceramic
      systems. Two surface treatments for the core surface finish and different
      veneering ceramics with different thermal expansion coefficients (TEC) were
      applied. The selected systems were two CAD-CAM ceramics; Cercon and Vita Mark II
      and one pressable system; (IPS)Empress 2 for layering technique. METHODS:
      Standardized core specimens were fabricated according to the manufacturer's
      instructions, or polished with 1200 siliconcarbide polishing paper. The core
      specimens were veneered with either its manufacturer's veneer or an experimental
      veneer with higher TEC. The obtained micro-bars were subjected to the
      microtensile bond strength test. The obtained data were analyzed using one and
      two-way ANOVA. A finite element analysis (FEA) model of the test setup was
      analyzed. Scanning Electron Microscopy (SEM) was carried out at the fracture
      surface. RESULTS: The core materials were significantly stronger than the
      veneering materials and the layered core-veneer specimens of which the results
      were statistically comparable. Polishing the core surfaces did not have an effect
      on the core-veneer bond strength. Experimental veneer with higher TEC resulted in
      massive fractures in both the core and veneering material. SEM and FEA
      demonstrated fracture pattern and mechanism of failure. SIGNIFICANCE: The core
      veneer bond strength is one of the weakest links of layered all-ceramic
      restorations and has a significant role in their success. To exploit fully the
      high strength of zirconium oxide cores, further research work is needed to
      improve its bond with its corresponding veneering material.

PMID- 16085303
TI  - Evaluation of blending effect of composites related to restoration size.
AB  - OBJECTIVE: It has been clinically observed that color differences between teeth
      and some restorations are smaller than if they are viewed in isolation. The
      objective was to evaluate in vitro the influence of restoration size, initial
      color difference and translucency on blending effect (BE) of resin composites.
      METHODS: Specimens were made of two composites (2CS, n = 5). The outer ring (D=10
      mm, 2-mm thick) was made of Palfique Estelite (PE, C2 shade), while the inner
      composites (D = 2-, 4-, and 6-mm, 2-mm thick) were PE and Esthet-X (EX, A2 and B2
      shades of both materials). Single-composite specimens (1CS) of all five shades (D
      = 10 mm, 2-mm thick, n = 5, batch) were made as well. Visual color assessments
      were done by six observers using a 1-5 scale. The BE were calculated as a
      difference in visual scores between corresponding 2CS and 1CS. 1CS were
      additionally evaluated using a spectrophotometer (D55, 10 degrees). Intra-and
      inter-observer agreements were tested. RESULTS: The blending effect for
      comparisons of PE/A2 for 2-, 4- and 6-mm inner composite was 2.7, 1.7, and 1.7,
      respectively. Lower values were recorded for PE/B2 (1.7, 1.2, and 1.1), EX/A2
      (0.3), 0.0, and 0.1) and EX/B2 (-0.2, -0.1, and -0.1). The correlation
      coefficient (r) among BE for 2-, 4-, and 6-mm inner composite (2CS) and deltaE*
      among batch shades and PE/C2 (1CS) were 0.98, 0.95, and 0.97, respectively.
      SIGNIFICANCE: Discovering and quantifying mechanisms of color shift of dental
      materials towards color of surrounding teeth may improve the esthetics of
      restorations and simplify shade matching.

PMID- 16085304
TI  - The frictional coefficients and associated wear resistance of novel low-shrink
      resin-based composites.
AB  - OBJECTIVES: Frictional forces play a major role in the oral wear process of
      dental resin-based composites (RBCs) and it would be of interest to consider how
      the energy from friction is dissipated at the material surface. Consequently, the
      micromechanical wear properties of conventional methacrylate compared with novel
      oxirane RBCs were assessed. METHOD: The frictional coefficient (mu), volume loss
      and Vickers hardness number (VHN) of oxirane (EXL596 and H1) and methacrylate
      RBCs (Z100 and Filtek Z250) were evaluated. Archard's wear equation was
      implemented to obtain the wear coefficient (K) and expressed as a 'fraction of
      friction' (K/micro) to indicate the dissipation of frictional energy that
      resulted in wear. Scanning electron microscopy (SEM) was used to qualitatively
      asses the wear facets of each RBC following 50000-cycles. RESULTS: The mean
      frictional coefficients observed between the oxirane and methacrylate RBCs were
      not significantly different (P > 0.05). However, the volume loss of EXL596 and H1
      (5.9 +/- 0.4 and 4.7 +/- 0.3 x 10(-2) mm(3)) was significantly increased compared
      with Z100 and Filtek Z250 (1.7 +/- 0.2 and 2.3 +/- 0.3 x 10(-2) mm(3)). The VHN
      of EXL596 and H1 was either significantly greater (P = 0.021) or similar (P =
      0.089) to Filtek Z250, respectively. An increase in K/micro was reported for
      EXL596 and H1 (34.7 +/- 4.1 and 22.8+ /- 2.4 x 10(-4)) compared with Z100 and
      Filtek Z250 (8.50 +/- 0.7 x 10(-4) and 8.62 +/- 1.0 x 10(-4)) (P < 0.05). SEM
      images of the oxirane RBCs exhibited increased surface fatigue and delamination
      of the surface layers compared with the methacrylate RBC specimens following
      50,000-cycles. CONCLUSION: The significant decrease in wear resistance of the
      oxirane compared with methacrylate RBCs was unexpected since frictional
      coefficients and/or surface hardness were statistically similar. The decreased
      wear resistance of EXL596 and H1 compared with Z100 and Filtek Z250 was further
      explained by the increase in K/micro from wear theory and the associated increase
      in surface fatigue identified from SEM. The simplistic testing procedure combined
      with SEM utilized in the current investigation provided a greater insight into
      the wear mechanism by considering the effect of frictional energy at the specimen
      surface which may benefit the development of improved wear resistance for
      experimental RBC materials.

PMID- 16085305
TI  - A pilot study of a simple photon migration model for predicting depth of cure in
      dental composite.
AB  - OBJECTIVES: The purpose of this study was to build a photo migration model to
      calculate the radiant exposure (irradiancextime) in dental composite and to
      relate the radiant exposure with extent of cure using polymer kinetics models.
      METHODS: A composite (Z100, Shade A2) cylinder (21 mm diameter by 15 mm deep) was
      cured with a tungsten-halogen lamp emitting 600 mW/cm2, 1 mm above the composite
      for 60s. For each of the 2x1 mm grids along the longitudinal cross section
      (diameter versus depth), the degree of conversion (DC) and hardness (KHN) were
      measured to construct the curing extent distribution. The inverse adding-doubling
      method was used to characterize the optical properties of the composite for the
      Monte Carlo model simulating the photon propagation within the composite
      cylinder. The calculated radiant exposure (H) distribution along the cross
      section was related to the curing extent DC/DC(max) distribution and fitted with
      two polymer curing kinetics models, the exponential model DC=DC(max)[1
      exp((ln0.5)H/H(dc)(50%))] and Racz's model [Formula: see text] , where H(dc)(50%)
      is a fitting parameter representing the threshold for 50% of the maximum curing
      level. RESULTS AND SIGNIFICANCE: The absorption and scattering coefficients of
      uncured composite were higher than that of cured composite at wavelengths between
      420 and 520 nm. A roughly hemi-spheric distribution of radiant exposure in the
      Monte Carlo simulation result was comparable with the curing profiles determined
      by both DC and KHN. The relationship between DC (or KHN) and H agreed with the
      Racz model (r2=0.95) and the exponential model (r2=0.93). The H(dc)(50%) was
      1.5(0.1), equal for the two models (P<0.05). The estimated radiant exposure
      threshold for 80% of the maximum curing level was between 3.8 and 8.8 J/cm2. The
      simulation results verify that the radiant exposure extends to a greater depth
      and width for composite with lower absorption and scattering coefficients. Given
      the optical properties and the geometry of the composite, and the spectrum and
      the geometry of the light source, the Monte Carlo simulation can accurately
      describe the radiant exposure distribution in a composite material to predict the
      extent of cure.

PMID- 16085306
TI  - Binary immobilization of tyrosinase by using alginate gel beads and
      poly(acrylamide-co-acrylic acid) hydrogels.
AB  - The use of the immobilized and the stable enzymes has immense potential in the
      enzymatic analysis of clinical, industrial and environmental samples. However,
      their widespread uses are limited due to the high cost of their production. In
      this study, binary immobilization of tyrosinase by using Ca-alginate and
      poly(acrylamide-co-acrylic acid) [P(AAm-co-AA)] was investigated. Maximum
      reaction rate (Vmax) and Michaelis-Menten constant (Km) were determined for the
      free and binary immobilized enzymes. The effects of pH, temperature, storage
      stability, reuse number and thermal stability on the free and immobilized
      tyrosinase were also examined. For the free and binary immobilized enzymes on Ca
      alginate and P(AAm-co-AA), optimum pH was found to be 7 and 5, respectively.
      Optimum temperature of the free and immobilized enzymes was observed to be 30 and
      35 degrees C, respectively. Reuse number, storage and thermal stability of the
      free tyrosinase were increased by a result of binary immobilization.

PMID- 16085307
TI  - Enthalpy relaxation of gelatin in the glassy state.
AB  - The enthalpy relaxation during the ageing of gelatin in the glassy state was
      studied for partially crystalline or amorphous materials at different water
      contents and ageing temperatures. The extent and rate of this relaxation
      associated with physical ageing were found to increase when the shifted
      temperature parameter (Ta-Tg) increased. This parameter was able to account for
      the effects of structure and water content (through Tg) and ageing temperature
      (Ta).

PMID- 16085308
TI  - Anisotropy and oxidative resistance of highly crosslinked UHMWPE after
      deformation processing by solid-state ram extrusion.
AB  - Solid-state deformation processing is a promising technique for modifying the
      physical and mechanical properties of highly crosslinked ultra-high molecular
      weight polyethylene (UHMWPE) beyond simple thermal treatment cycles that have
      been employed previously. This study evaluates anisotropy and oxidative
      resistance in a novel, radiation crosslinked (50 kGy) UHMWPE material (ArComXL:
      Biomet, Inc., Warsaw, IN), incorporating solid-state, deformation processing by
      extrusion below the melt transition for application in total hip arthroplasty.
      Tensile, compression, and small punch tests were conducted to evaluate the
      material properties in the three principal axes of the resulting material.
      Furthermore, short-term oxidative resistance was evaluated using Fourier
      transform infrared spectroscopy and the small punch test in conjunction with
      accelerated shelf aging protocols. The results of this testing indicate that the
      material is anisotropic, with significantly enhanced strength oriented along the
      long axis of the rod. For certain other properties, the magnitude of the
      anisotropy was relatively slight, especially in the elastic regime, in which only
      a 20% difference was noted between the long axis of the rod and the orthogonal,
      radial direction. The highly crosslinked material contains detectable free
      radicals, at a concentration that is 90% less than control, gamma inert
      sterilized UHMWPE. An unexpected finding of this study was evidence of oxidative
      stability of the deformation-processed material, even after 4 weeks of
      accelerated aging in a pressure vessel containing five atmospheres of oxygen
      (ASTM F2003), which resulted in macroscopic embrittlement of the control
      material. The oxidative stability observed in ArComXL suggests that the
      deformation-processed material may be suitable for air-permeable packaging and
      gas sterilization, which has thus far been reserved for remelted highly
      crosslinked UHMWPE.

PMID- 16085309
TI  - Calcium signaling and synaptic modulation: regulation of endocannabinoid-mediated
      synaptic modulation by calcium.
AB  - Postsynaptic Ca2+ signal influences synaptic transmission through multiple
      mechanisms. Some of them involve retrograde messengers that are released from
      postsynaptic neurons in a Ca2+-dependent manner and modulate transmitter release
      through activation of presynaptic receptors. Recent studies have revealed
      essential roles of endocannabinoids in retrograde modulation of synaptic
      transmission. Endocannabinoid release is induced by either postsynaptic Ca2+
      elevation alone or activation of postsynaptic Gq/11-coupled receptors with or
      without Ca2+ elevation. The former pathway is independent of phospholipase Cbeta
      (PLCbeta) and requires a large Ca2+ elevation to a micromolar range. The latter
      pathway requires PLCbeta and is facilitated by a moderate Ca2+ elevation to a
      submicromolar range. This facilitation is caused by Ca2+-dependency of receptor
      driven PLCbeta activation. The released endocannabinoids then activate
      presynaptic cannabinoid receptor type 1 (CB1), and suppress transmitter release
      from presynaptic terminals. Both CB1 receptors and Gq/11-coupled receptors are
      widely distributed in the brain. Thus, the endocannabinoid-mediated retrograde
      modulation may be an important and widespread mechanism in the brain, by which
      postsynaptic events including Gq/11-coupled receptor activation and Ca2+
      elevation can retrogradely influence presynaptic function.

PMID- 16085310
TI  - Cytotoxic effect of a lipophilic alkylating agent after incorporation into low
      density lipoprotein or emulsions: studies in human leukemic cells.
AB  - The use of low density lipoprotein (LDL) as drug carrier in acute myeloblastic
      leukemia chemotherapy is attractive due to high LDL uptake by leukemic cells.
      Lipid-based formulations, such as liposomes or microemulsions are promising
      alternatives. In the current study, we incorporated N-trifluoroacetyl-adriamycin
      14-valerate (AD32), a lipophilic derivative of daunorubicin (DNR), and WB4291, a
      lipophilic alkylating agent, into LDL or lipid microemulsions and evaluated their
      cytotoxic activities towards leukemic cell lines using as references DNR and
      melphalan. The incorporation of AD32 into LDL or emulsion resulted in complexes
      with poor cytotoxicity. WB4291-LDL and WB4291-emulsion exerted, on the other
      hand, promising cytotoxic effects towards parental and resistant K562 and HL60
      cell lines.

PMID- 16085311
TI  - Die hard: a blend of freezing and fleeing as a dynamic defense--implications for
      the control of defensive behavior.
AB  - Freezing, fleeing or fighting back are general defensive responses in many taxa.
      These defenses are mutually exclusive, since a prey cannot simultaneously flee
      and fight, or freeze and flee. Each of these defenses by itself is rudimentary
      and probably cannot provide a completely effective means to elude predation.
      Freezing is efficient only if employed before the prey is spotted by the
      predator, otherwise the prey becomes a stationary, easy to catch target. In
      fleeing, the prey can move directly away and maximize its distance from the
      predator, move toward the predator to confine it to a single clashing point, or
      dodge sideways to evade the attack. Prey can also run in a straight path that is
      efficient against slow or distant predators, or in a zigzag path that is
      efficient when a raptor is close or fast. In all, freezing and fleeing constitute
      together a complex and flexible defensive response, and are probably controlled
      by different motor systems that are inter-connected to allow fast switching
      between these behaviors, as required for an effective and versatile response.

PMID- 16085312
TI  - The effects of predator odors in mammalian prey species: a review of field and
      laboratory studies.
AB  - Prey species show specific adaptations that allow recognition, avoidance and
      defense against predators. For many mammalian species this includes sensitivity
      towards predator-derived odors. The typical sources of such odors include
      predator skin and fur, urine, feces and anal gland secretions. Avoidance of
      predator odors has been observed in many mammalian prey species including rats,
      mice, voles, deer, rabbits, gophers, hedgehogs, possums and sheep. Field and
      laboratory studies show that predator odors have distinctive behavioral effects
      which include (1) inhibition of activity, (2) suppression of non-defensive
      behaviors such as foraging, feeding and grooming, and (3) shifts to habitats or
      secure locations where such odors are not present. The repellent effect of
      predator odors in the field may sometimes be of practical use in the protection
      of crops and natural resources, although not all attempts at this have been
      successful. The failure of some studies to obtain repellent effects with predator
      odors may relate to (1) mismatches between the predator odors and prey species
      employed, (2) strain and individual differences in sensitivity to predator odors,
      and (3) the use of predator odors that have low efficacy. In this regard, a small
      number of recent studies have suggested that skin and fur-derived predator odors
      may have a more profound lasting effect on prey species than those derived from
      urine or feces. Predator odors can have powerful effects on the endocrine system
      including a suppression of testosterone and increased levels of stress hormones
      such as corticosterone and ACTH. Inhibitory effects of predator odors on
      reproductive behavior have been demonstrated, and these are particularly
      prevalent in female rodent species. Pregnant female rodents exposed to predator
      odors may give birth to smaller litters while exposure to predator odors during
      early life can hinder normal development. Recent research is starting to uncover
      the neural circuitry activated by predator odors, leading to hypotheses about how
      such activation leads to observable effects on reproduction, foraging and
      feeding.

PMID- 16085313
TI  - Acoustic characteristics of air puff-induced 22-kHz alarm calls in direct
      recordings.
AB  - Alarm calls were induced in adult Wistar rats by an air puff. Emitted calls were
      digitized and directly recorded on a computer hard drive. The long-duration 22
      kHz calls were emitted almost exclusively in series. Initial calls in the series
      tended to have the longest durations, higher frequency range, and the highest
      degree of frequency modulation, as compared to other calls. The frequency
      modulation always appeared as a downward sweep and seemed to represent a tuning
      of individual calls to a 3 kHz communicatory band. Regardless of the maximum
      frequency, rats always reached approximately the same minimum frequency, common
      to all calls. Thus, the broader was the frequency range of a given call, the
      longer the call duration. It is postulated, therefore, that rats emit 22-kHz
      calls at the minimum possible ultrasonic frequency they are able to produce,
      which is synonymous with peak frequency. It is further postulated that production
      of alarm calls in series, with long call duration and the invariably low
      ultrasonic frequency, maximizes successful communication in dangerous situations.
      Exceptions to this rule were observed immediately following air puffs, suggesting
      that acoustic parameters of the initial calls may differ from the alarming
      properties of the remaining 22-kHz calls.

PMID- 16085314
TI  - Scenes from the museum: the hermaphrodite monkey and stage management at La
      Specola.
AB  - How can a natural history collection be turned into an instrument of public
      education? What should an institution serving such a purpose look like? Everyday
      scenes from the Royal Museum of Physics and Natural History in Florence, founded
      in 1775, highlight the practical problems with transforming a museum in such a
      fashion. Naturalists employed at the Royal Museum took measures to control both
      its "frontstage" (the public exhibition) and its "backstage" (the offices and
      workshops) in an effort to secure the integrity of the educational and scientific
      mission of the new institution.

PMID- 16085315
TI  - Effects of renal failure on drug transport and metabolism.
AB  - Renal failure not only alters the renal elimination, but also the non-renal
      disposition of drugs that are extensively metabolized by the liver. Although
      reduced metabolic enzyme activity in some cases can be responsible for the
      reduced drug clearance, alterations in the transporter systems may also be
      involved in the process. With the development of renal failure, the renal
      secretion of organic ions mediated by organic anion transporters (OATs) and
      organic cation transporters (OCTs) is decreased. 3-Carboxy-4-methyl-5-propyl-2
      furanpropanoic acid (CMPF) and other organic anionic uremic toxins may directly
      inhibit the renal excretion of various drugs and endogenous organic acids by
      competitively inhibiting OATs. In addition, the expression of OAT1 and OCT2 was
      reduced in chronic renal failure (CRF) rats. Renal failure also impairs the liver
      uptake of drugs and organic anions, such as bromosulphophthalein (BSP),
      indocyanine green (ICG), and thyroxine, where organic anion transport
      polypeptides (OATPs) are the major transporters. Most previous studies have been
      done in animals or cell culture, very often in rat models, but these are presumed
      to reflect the presentation of advanced renal disease in humans as well. Recent
      studies demonstrate that the uremic toxins CMPF and indoxyl sulfate (IS) can
      directly inhibit rOatp2 and hOATP-C in hepatocytes. The protein content of the
      liver uptake transporters Oatp1, 2, and 4 were significantly decreased in CRF
      rats. Decreased activity of the intestinal efflux transporter, P-glycoprotein (P
      gp), was also observed in CRF rats, with no significant change of protein
      content, suggesting that uremic toxins may suppress P-gp function. However,
      increased protein levels of multidrug resistance-associated protein (MRP) 2 in
      the kidney and MRP3 in the liver were found in CRF rats, suggesting an adaptive
      response that may serve as a protective mechanism. Increases in drug areas under
      the curve (AUCs) in subjects with advanced renal disease for drugs that are not
      renally excreted are consistent with uremic toxin effects on either intestinal or
      hepatic cell transporters, metabolizing enzymes, or both. In conclusion,
      alterations of drug transporters, as well as metabolic enzymes, in patients with
      renal failure can be responsible for reduced drug clearance.

PMID- 16085316
TI  - In situ measurement of neuronal nitric oxide synthase activity in the spinal cord
      by NADPH-diaphorase histochemistry.
AB  - NADPH-diaphorase (NADPH-d) histochemistry has provided a simple method to stain
      neuronal nitric oxide synthase (nNOS)-containing neurons in the central nervous
      system. In the spinal cord, NO formation following activation of N-methyl-D
      asparate (NMDA) receptors plays a crucial role in nociceptive processing. To
      investigate the molecular mechanisms, we attempted to evaluate nNOS activity in
      situ using isolated intact spinal cord preparation and NADPH-d histochemistry.
      NADPH-d activity in the superficial layer of the spinal cord increased gradually
      with ages from P10 to P30 and NMDA enhanced the NADPH-d staining in a time- and
      concentration-dependent manner. The NMDA-stimulated NADPH-d staining was
      inhibited by NMDA receptor antagonists, but not by non-NMDA and metabotropic
      glutamate receptor antagonists. The NADPH-d staining showed a pronounced
      stereospecificity for beta-NADPH and completely suppressed by
      dichlorophenolindophenol, an artificial electron acceptor. NMDA-evoked NO
      formation in the spinal cord was confirmed by the fluorescent NO indicator
      diaminofluorescein-FM (DAF-FM). These results demonstrate that NADPH-d activity
      in the superficial spinal cord is ascribed to nNOS activity and is dependent on
      NMDA. A combination of isolated intact spinal cord preparations and NADPH-d
      histochemistry may provide a unique system to elucidate biochemical and molecular
      mechanisms for nNOS activation in the spinal cord.

PMID- 16085317
TI  - Efficient spike-sorting of multi-state neurons using inter-spike intervals
      information.
AB  - We demonstrate the efficacy of a new spike-sorting method based on a Markov chain
      Monte Carlo (MCMC) algorithm by applying it to real data recorded from Purkinje
      cells (PCs) in young rat cerebellar slices. This algorithm is unique in its
      capability to estimate and make use of the firing statistics as well as the spike
      amplitude dynamics of the recorded neurons. PCs exhibit multiple discharge
      states, giving rise to multi-modal inter-spike interval (ISI) histograms and to
      correlations between successive ISIs. The amplitude of the spikes generated by a
      PC in an "active" state decreases, a feature typical of many neurons from both
      vertebrates and invertebrates. These two features constitute a major and
      recurrent problem for all the presently available spike-sorting methods. We first
      show that a hidden Markov model with three log-normal states provides a flexible
      and satisfying description of the complex firing of single PCs. We then
      incorporate this model into our previous MCMC based spike-sorting algorithm
      [Pouzat C, Delescluse M, Viot P, Diebolt J. Improved spike-sorting by modeling
      firing statistics and burst-dependent spike amplitude attenuation: a Markov chain
      Monte Carlo approach. J Neurophysiol 2004;91:2910-28] and test this new algorithm
      on multi-unit recordings of bursting PCs. We show that our method successfully
      classifies the bursty spike trains fired by PCs by using an independent single
      unit recording from a patch-clamp pipette.

PMID- 16085318
TI  - ELISA methods to measure cholinergic markers and nerve growth factor receptors in
      cortex, hippocampus, prefrontal cortex, and basal forebrain from rat brain.
AB  - The central cholinergic system has a fundamental role in normal cognitive
      function, and in diseases that exhibit cognitive dysfunction. The purpose of this
      study was to design ELISA methods to measure proteins that have essential
      functions in the central cholinergic system. We were particularly interested in
      quantifying proteins that respond directly or indirectly to nerve growth factor
      (NGF). ELISAs offer advantages over Western blot analyses and other methods, such
      as increased sensitivity, decreased assay variability, increased efficiency, and
      decreased cost. We developed indirect ELISA methods for: choline
      acetyltransferase (ChAT); the vesicular acetylcholine transporter (VAChT); the
      high affinity choline transporter (HACT/CHT); TrkA, the high affinity NGF
      receptor; the p75 neurotrophin receptor (p75(NTR)). A sandwich ELISA was
      developed to measure tyrosine-phosphorylated TrkA in brain lysates. We used these
      ELISAs to compare levels of the above proteins in important memory-related brain
      regions--basal forebrain, hippocampus, cortex, and prefrontal cortex--from old
      and young rats. We identified age-related differences in the levels of the
      aforementioned proteins (e.g., VAChT and HACT/CHT in hippocampus). Thus, these
      ELISA methods should be particularly useful for comparing the effects of age,
      disease, drugs, and toxicants on brain levels of key cholinergic and growth
      factor-related proteins.

PMID- 16085319
TI  - Prenatal stress may increase vulnerability to life events: comparison with the
      effects of prenatal dexamethasone.
AB  - Prenatal stress has been associated with a variety of alterations in the
      offspring. The presented observations suggest that rather than causing changes in
      the offspring per se, prenatal stress may increase the organism's vulnerability
      to aversive life events. Offspring of rat dams stressed gestationally by chronic
      mild stress (CMS, a variable schedule of different stressors) or dexamethasone
      (DEX, a synthetic glucocorticoid, i.e., a pharmacological stressor) was tested
      for reactivity by testing their acoustic startle response (ASR). Two subsets of
      offspring were tested. One was experimentally naive at the time of ASR testing,
      whereas the other had been through blood sampling for assessment of the hormonal
      stress response to restraint, 3 months previously. Both prenatal CMS and
      dexamethasone increased ASR in the offspring compared to controls, but only in
      prenatally stressed offspring that had been blood sampled 3 months previously. In
      conclusion, similarity of the effects of maternal gestational exposure to a
      regular stress schedule and of exposure to a synthetic glucocorticoid suggests
      that maternal glucocorticoids may be a determining factor for changes in the
      regulatory mechanisms of the acoustic startle response. Further, a single
      aversive life event showed capable of changing the reactivity of prenatally
      stressed offspring, whereas offspring of dams going through a less stressful
      gestation was largely unaffected by this event. This suggests that circumstances
      dating back to the very beginning of life affect the individual's sensitivity
      towards experiences in life after birth. The prenatal environment may thus form
      part of the explanation of the considerable individual variation in the
      development of psychopathology.

PMID- 16085320
TI  - Chronic rhinosinusitis in congenital craniofacial malformations.
AB  - OBJECTIVES: To review developmental abnormalities and iatrogenic alterations in
      sinus anatomy that may predispose patients with congenital craniofacial
      malformations to chronic rhinosinusitis. STUDY DESIGN: Retrospective study.
      METHODS: Seven patients with craniofacial malformations who were surgically
      treated by the senior author were included in the study. All were diagnosed with
      chronic rhinosinusitis refractory to medical management. Four patients had
      undergone previous corrective craniofacial surgery, and three of these patients
      developed iatrogenic sinus disease. Demographic data, diagnoses and anatomical
      abnormalities were included. RESULTS: Abnormal sinus anatomy was present in all
      patients, most commonly skull base abnormalities and dehiscent lamina papyracea.
      All patients underwent successful endoscopic surgical management (n = 7) for
      their chronic rhinosinusitis. Two patients had adjuvant external procedures.
      There were no complications and no recurrences after a mean follow up time of 15
      months. CONCLUSIONS: Otolaryngologists should be aware of the possibility of
      chronic rhinosinusitis in patients with craniofacial malformations. Careful
      preoperative evaluation of radiographic studies should be performed as most of
      these patients will have abnormal sinus anatomy. In addition, patients who
      undergo surgery to correct their craniofacial malformations are susceptible to
      altered sinus anatomy that may predispose them to the development of iatrogenic
      chronic rhinosinusitis.

PMID- 16085321
TI  - Primary lacrimal sac non-Hodgkin's lymphoma in a child.
AB  - Primary lacrimal sac lymphoma is extremely rare in children. To our knowledge,
      only two previous cases have been reported in the literature. Here, we report the
      case of a 9-year-old girl with primary lacrimal sac lymphoma who has recurrent
      mass.

PMID- 16085322
TI  - Ten-year outcome of newborn hearing screening in Austria.
AB  - OBJECTIVE: Current health care standards recommend that congenital hearing loss
      be confirmed before age three months and intervened for before age six months.
      This study evaluated to what extent the Austrian universal neonatal hearing
      screening (UNHS) program achieves this goal. The Austrian UNHS program is a
      hospital-based, two-stage screen based on transient oto-acoustic emissions, as
      promoted in 1995 in a position paper of the Austrian ENT Society. METHODS:
      Retrospective chart review and data analysis. All Austrian institutions engaged
      in the diagnosis and treatment of childhood hearing loss were requested to
      provide their data on children with permanent congenital sensorineural hearing
      impairment registered since 1990. Children who had undergone hearing screening,
      were compared to those who had not. Main outcome measures were age at
      confirmation of and age at intervention for the hearing loss. In each group, the
      percentage of children, whose hearing loss was confirmed by age three months, and
      intervened for by age six months, was determined. RESULTS: Data from 321 hearing
      impaired children were useable. Of these children, 167 were screened and 154 were
      not. At age three months, a hearing loss was diagnosed in 35% of screened
      children, but in only 2% of unscreened. These percentages rose to 69% and 6%,
      respectively, at age six months and to 81% and 12%, respectively, at age one
      year. Intervention mostly started within less than one month after diagnosis. At
      age six months, 61% of screened children, but only 4% of unscreened children, had
      undergone intervention. CONCLUSIONS: Hearing screening enormously increases the
      number of early-detected children. However, in quite a few screened children
      hearing loss is neither confirmed within three months after birth, nor intervened
      for within six months after birth. Reasons for the delay must be paid attention
      in order to warrant that UNHS can be as effective as possible.

PMID- 16085324
TI  - Different MRI findings for normal elderly and very mild Alzheimer's disease in a
      community: implications for clinical practice the Tajiri Project.
AB  - To investigate magnetic resonance imaging (MRI) findings of very mild dementia,
      485 participants were randomly selected in a community. Three hundred and forty
      participants were of Clinical Dementia Rating (CDR) 0 (healthy), 113 were of CDR
      0.5 (questionable dementia), and 32 were of CDR 1 and 2 (including 20 Alzheimer's
      disease, AD). Cortical atrophy, white matter lesion, etc., were visually
      assessed. We found that each part of the brain showed atrophy in older adults for
      CDR 0. For CDR 0.5, the relationships between MRI findings and age were weaker,
      and for AD, there were no such relationship. Atrophy related with dementia
      severity was found to be limited to the lateral and medial temporal lobes. For
      CDR 0.5, amygdala atrophy was the only finding indicating CDR effect but no age
      effect. The amygdala or anterior entorhinal atrophy is important for
      discriminating very mild dementia from normal elderly.

PMID- 16085325
TI  - Plasma triglycerides, an independent predictor of cardiovascular disease in men:
      a prospective study based on a population with prevalent metabolic syndrome.
AB  - BACKGROUND AND METHODS: We aimed to assess whether fasting plasma triglycerides
      independently predicted future fatal and nonfatal cardiovascular disease (CVD) in
      a population having a high prevalence of the metabolic syndrome. In the Turkish
      Adult Risk Factor Study, a population-based survey, 2682 men and women 20 years
      of age or over with fasting triglyceride values available and free of CVD at
      baseline examination in 1990, were prospectively followed up till 2003/04.
      Triglyceride concentrations were measured by the enzymatic dry chemistry method
      and stratified into sex-specific quintiles. Information on the mode of death was
      obtained from first-degree relatives and/or health personnel of local health
      office. Diagnosis of coronary heart disease and stroke among survivors was based
      on history, physical examination of the cardiovascular system and Minnesota
      coding of resting electrocardiograms. A total of 120 fatal and 221 new nonfatal
      CVD occurred among adults (mean age 43+/-14) during a mean 9.3 years of follow
      up. RESULTS: CVD was significantly and independently predicted by the top versus
      the bottom fasting triglyceride quintile in logistic regression analyses when
      adjusted for age, sex, BMI, systolic blood pressure, total cholesterol, lipid
      lowering medication, status of smoking and of glucose regulation (relative risk
      [RR] in men and all adults 2.38 and 1.79, respectively, p both <0.02). This
      corresponded to hazard ratios (HR) of 1.43 in men and 1.28 in men and women
      combined. Adjustment for HDL-cholesterol instead of total cholesterol in the same
      model gave also significant HRs corresponding to 1.42 in men and 1.32 in sexes
      combined. CONCLUSIONS: Fasting triglycerides are predictive of future CVD among
      men with an HR of 1.4, independent of age, diabetes, lipid-lowering medication,
      traditional risk factors including total cholesterol or HDL-C, in a population in
      which metabolic syndrome prevails. A modest independent risk increment in women
      did not reach significance.

PMID- 16085326
TI  - Myocardial infarction redefined: impact on case-load and outcome of patients with
      suspected acute coronary syndrome and nondiagnostic ECG at presentation.
AB  - Risk stratification of chest pain (CP) is still debated. Objective of this study
      was to evaluate the performance of a risk stratification model for patients with
      suspected acute coronary syndrome (ACS) and nondiagnostic ECG at presentation, in
      whom the occurrence of myocardial infarction was either diagnosed following
      traditional (t-MI) or the recently redefined (r-MI) criteria. First-line 6-h work
      up categorized 3068 patients with suspected ACS and nondiagnostic ECG into low
      risk for short-term coronary events, intermediate-risk who entered second-line
      work-up, and high-risk. Intermediate-risk patients with positive second-line work
      up and high-risk patients were considered for urgent coronary angiography.
      Angina, non-fatal MI, sudden death, and revascularization constituted composite
      end-point (CE) for in-hospital and 6-month outcome. ACS incidence was 16%; r-MI
      increased by 62% the diagnosis of MI over t-MI. Among 2024 discharged low-risk
      patients, 12 (0.6%) had non-fatal CE at 6 months. ACS was diagnosed in 19% of 503
      intermediate-risk and 96% of 389 high-risk patients. Among ACS patients, in
      hospital CE occurred in 14% of t-MI, 7% of r-MI, and 9% of unstable angina (UA)
      patients (t-MI vs. r-MI and t-MI vs. UA: p<0.05, for both); 6-month CE occurred
      in 23%, 16% and 12% of t-MI, r-MI and UA, respectively (t-MI vs. UA: p<005).
      Sensitivity, specificity and accuracy were high both for diagnostic (97%, 98%,
      99%, respectively) and treatment (83%, 98%, 97%, respectively) strategy. Risk
      stratification, and categorization according to traditional or redefined MI and
      UA criteria allow safe allocation of resources in CP patients with suspected ACS
      and nondiagnostic ECG at presentation because outcome is accurately predicted.

PMID- 16085327
TI  - Improved methods for the cultivation of the chemolithoautotrophic bacterium
      Nitrosomonas europaea.
AB  - The chemolithoautotrophic nitrifier Nitrosomonas europaea is useful for
      biotechnological processes such as bioremediation of toxic chemicals, as well as
      playing an essential role in the global nitrogen cycle. To successfully apply
      this bacterium in biotechnology, large quantities of active cells need to be
      produced. In this paper we demonstrate improved methods for mass cultivation of
      N. europaea. A doubling in the final cell density to 30 mg dry wt l(-1) was
      achieved with a fed-batch culture technique using ammonium bicarbonate or sodium
      bicarbonate for pH control. The cells displayed high ammonia oxidizing activity
      in excess of 20 mmol g(-1) dry wt h(-1). Continuous culture under energy limited
      growth conditions (<0.1 mM residual ammonium) in a bench scale bioreactor using a
      microfiltration membrane for high cell recycle produced final culture densities
      greater than 350 mg dry wt l(-1). This system allowed operator controlled
      culturing of cells under excess substrate as well as energy limited growth
      conditions with a maximum ammonium oxidation potential in excess of 250 mmol g(
      1) dry wt h(-1).

PMID- 16085328
TI  - Polyamino acids as synthetic enzymes: mechanism, applications and relevance to
      prebiotic catalysis.
AB  - Polyamino acids, such as polyleucine, behave as synthetic enzymes in the
      asymmetric epoxidation of chalcone and other electron-deficient alkenes (the
      Julia-Colonna reaction). The influences of reaction conditions, of the molecular
      structure of the catalysts and of the scaling-up of the process on the
      enantioselectivity of the reaction have been determined. The kinetics and
      mechanism have been investigated using a soluble PEG-polyleucine conjugate, which
      behaves in a similar way to an enzyme, showing saturation kinetics for both
      chalcone and HOO-. Enantioselective catalysis is achieved with peptides with as
      few as five residues and scalemic catalysts show high chiral amplification. Here,
      we discuss the relevance of these-enzyme like catalysts to prebiotic processes,
      such as the role of small peptides in the formation of optically active
      cyanohydrins.

PMID- 16085323
TI  - Gene discovery in Plasmodium vivax through sequencing of ESTs from mixed blood
      stages.
AB  - Despite the significance of Plasmodium vivax as the most widespread human malaria
      parasite and a major public health problem, gene expression in this parasite is
      poorly understood. To accelerate gene discovery and facilitate the annotation
      phase of the P. vivax genome project, we have undertaken a transcriptome approach
      to study gene expression in the mixed blood stages of a P. vivax field isolate.
      Using a cDNA library constructed from purified blood stages, we have obtained
      single-pass sequences for approximately 21,500 expressed sequence tags (ESTs),
      the largest number of transcript tags obtained so far for this species. Cluster
      analysis revealed that the library is highly redundant, resulting in 5407
      clusters. Clustered ESTs were searched against public protein databases for
      functional annotation, and more than one-third showed a significant match, the
      majority of these to Plasmodium falciparum proteins. The most abundant clusters
      were to genes encoding ribosomal proteins and proteins involved in metabolism,
      consistent with the predominance of trophozoites in the field isolate sample. In
      spite of the scarcity of other parasite stages in the field isolate, we could
      identify genes that are expressed in rings, schizonts and gametocytes. This study
      should facilitate our understanding of the gene expression in P. vivax asexual
      stages and provide valuable data for gene prediction and annotation of the P.
      vivax genome sequence.

PMID- 16085329
TI  - Prevalence of pigs infected by Salmonella Typhimurium at slaughter after an
      enterocolitis outbreak.
AB  - A cross-sectional study was performed to estimate the prevalence of slaughter
      pigs infected by Salmonella typhimurium after an enterocolitis outbreak in a
      commercial pig farm, which was characterised by diarrhoea during the growing
      phase. Anatomopathological and histopathological findings were suggestive of
      salmonellosis, which was further confirmed by isolation of S. typhimurium from
      organs and faeces samples from diseased animals. Ileocolic lymph nodes were
      aseptically collected from 43 pigs during slaughter procedures. The estimated
      prevalence of Salmonella-infected pigs was 53.48% [confidence interval (CI):
      42.94:64.02%]. This finding demonstrates that the carriage of S. typhimurium at
      slaughter might be high if pigs originate from a batch previously affected by
      Salmonella-enterocolitis outbreak at the pre-harvest pork production chain.

PMID- 16085330
TI  - Use of a culture-independent molecular method to study the ecology of Yersinia
      spp. in food.
AB  - A culture-independent method for the direct detection in food of Yersinia spp.
      was developed in this study. It is based on the amplification of a 359 bp PCR
      product from the RNA polymerase beta-subunit gene (rpoB) and subsequent analysis
      by denaturing gradient gel electrophoresis (DGGE). Direct detection of Yersinia
      spp. by PCR-DGGE was carried out in ready-to-eat vegetables and the results
      compared with the results of the traditional, culture-dependent method. The DGGE
      profiles were determined to be species-specific. As a matter of fact, Yersinia
      enterocolitica, Yersinia intermedia, Yersinia frederiskenii and Yersinia
      kristensenii showed differential migrations in the gels. Moreover, Y.
      enterocolitica serotypes O:3, O:5 and O:9 were distinguishable, as well. Only for
      a limited number of traditionally isolated strains, the biochemical and molecular
      identification agree. In particular, an overestimation of Y. enterocolitica, as
      determined biochemically, was observed. Finally when the protocol was applied to
      27 food samples, a good correlation was obtained when the results of traditional
      and direct methods were analyzed. The molecular method was able to identify Y.
      enterocolitica, not detected by plating analysis. However, for 4 samples, that,
      by plating analysis, were determined to contain Yersinia spp., no PCR product
      could be obtained after enrichment, probably due to low numbers of target cells,
      thereby not allowing the possibility to perform DGGE analysis. The protocol
      described here represents a reliable tool for the detection of Yersinia spp. in
      food, which can be used to obtain the needed results faster than with traditional
      culturing methods.

PMID- 16085331
TI  - Rational selection of Leuconostoc strains for mixed starters based on the
      physiological biodiversity found in raw milk fermentations.
AB  - The technological abilities of eleven wild Leuconostoc strains isolated from
      artisanal Afuega'l Pitu cheese, a homemade acid-coagulated cheese from raw milk
      from Asturias (northern Spain), were studied in order to test their potential
      application as components of dairy starters. Metabolic activity, production of
      flavour compounds, resistance to NaCl, acid, nisin and freezing, as well as
      genetic biodiversity were investigated. Marked differences among all tested
      strains reflected the existing biodiversity in naturally fermented products.
      After evaluation of their performance, strains IPLA567 and IPLA979 revealed the
      best properties to be used use in mixed dairy starter cultures. These two strains
      were able to ferment lactose and galactose and produced larger amounts of lactic
      acid than the others. Moreover, they showed high tolerance levels to NaCl, acid
      and nisin, although their resistance to freezing was slightly lower than the
      other strains. This study evidences the fact that natural environments can be
      considered as a proper source of new strains, which may help the dairy industry
      to widen their fermented products range.

PMID- 16085332
TI  - An in vitro evaluation of PCL-TCP composites as delivery systems for platelet
      rich plasma.
AB  - In this study, we first investigated the in vitro degradation properties of
      biodegradable, bioresorbable polycaprolactone-20% tricalcium phosphate (PCL-TCP)
      composites immersed in simulated body fluid (SBF) and phosphate buffered saline
      (PBS). Then, the release profiles of the growth factors present in platelet-rich
      plasma (PRP) loaded onto the composites incubated in SBF and PBS were compared.
      Composites immersed in both buffers showed water uptake of 13.7%+/-0.75 at day 1,
      followed by a constant uptake of 12.1%+/-0.3 until day 12. Henceforth the water
      uptake declined for SBF- and increased for PBS-soaked composites. The weight loss
      data did not reveal any trend. SBF- and PBS-soaked samples displayed 1-2% weight
      loss for 2 and 5 of the ten time points measured respectively. The original
      protein retention (PR) of the composites was 49.1%+/-1.50. After immersion in SBF
      and PBS for 4 weeks, the PR was augmented to 88.5%+/-1.40 and 69.1%+/-1.40
      correspondingly. PRP after activation contained 164.7+/-24.8, 194+/-43 and 18.3+/
      4.75 ng/ml of TGF-beta1, PDGF-BB and IGF-1. Microscopic analysis verified the
      attachment of PRP to the rods and pores of the composites. Interestingly, the
      buffers played an important role in determining the release profiles of TGF and
      PDGF. Firstly, PBS-soaked composites manifested a tri-phasic burst-like profile
      that was absent in SBF. Secondly, SBF-soaked composites experienced delayed
      release of the growth factors and total release was not achieved (64.4% for TGF
      and 60.5% for PDGF), whereas total release was realized for PBS-soaked
      composites. Lastly, release profiles from SBF-soaked composites were growth
      factor mediated in terms of their amounts and sizes. This was not observed for
      PBS-soaked composites. IGF-1, on the other hand, exhibited a progressive
      reduction in levels over the entire experimental period for both buffers. The
      mechanisms of release were theorized to be a combination of diffusion,
      degradation and bioactivity. Since SBF is analogous to our body fluids in terms
      of its ionic constituents, we expect the elution profiles derived from SBF-soaked
      samples to more accurately emulate the in vivo situation. In conclusion, this
      study has deemed PCL-TCP composites as suitable delivery systems for platelet
      rich plasma.

PMID- 16085333
TI  - Adenosine monophosphate-activated protein kinase and nitric oxide in rat
      steatotic liver transplantation.
AB  - BACKGROUND/AIMS: Hepatic steatosis is a risk factor for transplantation. We
      examined the role of AMP-activated protein kinase (AMPK) and nitric oxide (NO) in
      the benefits of preconditioning in steatotic liver transplantation. METHODS:
      Steatotic liver transplantation with or without preconditioning was induced in
      Zucker rats. The activities of AMPK and NO synthase (NOS) were measured and
      altered pharmacologically. RESULTS: Preconditioning or AMPK activation with
      aminoimidazole-4-carboxamide ribonucleoside (AICAR) increased AMPK and
      constitutive NOS activities and protected against lipid peroxidation,
      nitrotyrosine formation and hepatic injury in both grafts. Inhibition of AMPK
      activity removed the benefits of preconditioning. NO synthesis inhibition
      abolished the benefits of preconditioning or AICAR. Therefore, preconditioning or
      AICAR, through AMPK activation, may induce NO synthesis, thus protecting against
      hepatic injury in both steatotic and non-steatotic liver transplantation. In non
      steatotic grafts, NO donors simulated the benefits of preconditioning. However,
      in steatotic grafts, NO supplementation was ineffective. CONCLUSIONS: These
      results indicate (a) a potential relationship between AMPK and NO in the benefits
      of preconditioning in steatotic liver transplantation, (b) AICAR as a new
      phamacological strategy in steatotic liver transplantation and (c) a differential
      effect of NO supplementation in both grafts.

PMID- 16085334
TI  - Neutral endopeptidase (EC 3.4.24.11) in cirrhotic liver: a new target to treat
      portal hypertension?
AB  - BACKGROUND/AIMS: In liver cirrhosis atrial natriuretic peptide (ANP) decreases
      portal vascular resistance and tributary flow. The enzyme neutral endopeptidase
      (NEP) degrades ANP and bradykinin and generates endothelin-1 from big-endothelin.
      We determined the effects of NEP inhibition by candoxatrilat on hormonal status,
      liver function and arterial and portal pressures in rats with CCl4-induced
      cirrhosis. METHODS: Two groups of seven control rats received 1 ml 5% glucose
      solution alone or containing 10 mg/kg candoxatrilat; three groups of 10 ascitic
      cirrhotic rats received placebo, 5 or 10 mg/kg candoxatrilat. NEP protein
      concentration and immunostaining were analyzed in normal and cirrhotic livers.
      RESULTS: In cirrhotic rats 10 mg/kg candoxatrilat significantly increased steady
      state indocyanine green clearance (a parameter reflecting liver plasma flow)
      (P<0.01), decreased portal pressure (P<0.01), had no effect on arterial pressure
      and plasma renin activity but increased ANP plasma levels (P<0.05) and urinary
      excretions (P<0.01) of ANP and cGMP. In the cytosol fraction of rat cirrhotic
      livers a 280% increase in NEP content was found (P<0.01), chiefly localized in
      desmin-positive myofibroblast-like cells of fibrous septa. CONCLUSIONS:
      Candoxatrilat has few effects on systemic hemodynamics and hormonal status; its
      portal hypotensive action depends on effects exerted on intrahepatic vascular
      resistance.

PMID- 16085335
TI  - Adenovirus-mediated overexpression of the activin betaC subunit accelerates liver
      regeneration in partially hepatectomized rats.
AB  - BACKGROUND/AIMS: The expression level of the activin betaC subunit is high in
      normal liver and reduces after partial hepatectomy, but its function is
      controversial. METHODS: To determine the role of the betaC subunit during liver
      regeneration, we overexpressed the betaC subunit gene in the liver by infusing
      adenovirus vector encoding the flag-tagged betaC subunit into the portal vein.
      Adenovirus vector encoding the beta-galactosidase was also infused as a control.
      Seventy percent hepatectomy was performed 4 days after the infection. RESULTS:
      Approximately 20% of hepatocytes expressed the flag-tagged betaC subunit at the
      time of hepatectomy and approximately 50% of hepatocytes expressed the betaC
      subunit 3 days after hepatectomy. In betaC-infected liver, bromodeoxyuridine
      labeling was significantly greater at 24 and 48 h after partial hepatectomy
      compared with the control liver. Consistent with this observation, the liver
      regeneration rate was significantly greater in betaC-transfected liver at 72 and
      96 h after hepatectomy. Many of the bromodeoxyuridine-positive nuclei were
      observed in or by the betaC-transfected hepatocytes. CONCLUSIONS: These results
      indicate that liver regeneration is accelerated in betaC-overexpressing liver.
      The betaC subunit may function to promote replication of hepatocytes during liver
      regeneration.

PMID- 16085336
TI  - Monitoring groundwater contamination and delineating source zones at industrial
      sites: uncertainty analyses using integral pumping tests.
AB  - Field-scale characterisations of contaminant plumes in groundwater, as well as
      source zone delineations, are associated with uncertainties that can be
      considerable. A major source of uncertainty in environmental datasets is due to
      variability of sampling results, as a direct consequence of the heterogeneity of
      environmental matrices. We develop a methodology for quantifying uncertainties in
      field-scale mass flow and average concentration estimations, using integral
      pumping tests (IPTs), where the contaminant concentration is measured as a
      function of time in a pumping well. This procedure increases the sampling volume
      and reduces the effect of small-scale variability that may bias point-scale
      measurements. In particular, using IPTs, the interpolation uncertainty of
      conventional point-scale measurements is transformed to a quantifiable
      uncertainty related to the (unknown) plume position relative to the pumping well.
      We show that this plume position uncertainty generally influenced the predicted
      mass flows and average concentrations (of acenapthene, benzene and CHCs) to a
      greater extent than a boundary condition uncertainty related to the local water
      balance, considering 19 control planes at a highly heterogeneous industrial site
      in southwest Germany. Furthermore, large (order of magnitude) uncertainties only
      occurred if the conditions were strongly heterogeneous in the nearest vicinity of
      the well. We also develop a consistent methodology for an assessment of the
      combined effect of uncertainty in hydraulic conditions and uncertainty in
      reactive transport parameters for delimiting of both contaminant source zones and
      zones absent of source, based on (downgradient) IPTs.

PMID- 16085337
TI  - Ion selectivity of scorpion toxin-induced pores in cardiac myocytes.
AB  - The lytic activity of parabutoporin (PP) and opistoporin 1 (OP1) on mammalian and
      bacterial membranes have been described. We investigated pore-formation and ion
      selectivity in cardiac myocytes by measuring the whole cell leak current by means
      of the patch clamp technique. Pore formation was observed as the induction of
      leak currents. Ion selectivity of the pores was indicated by the shift of the
      reversal potential (E(rev)) upon substitution of intra- and extra-cellular ions.
      Results were compared with the effect of gramicidin A (gramA). PP and OP1 induced
      a fluctuating leak current and indicate non-selectivity of PP-induced pores. PP-
      and OP1-induced pores are between 1.38 and 1.78 nm in diameter.

PMID- 16085338
TI  - Axonal degeneration affects muscle density in older men and women.
AB  - Using data from InCHIANTI, a prospective population-based survey of older
      persons, we examined the relationship of peroneal nerve conduction velocity (NCV,
      a measure of nerve myelination) and compound muscle action potential (CMAP, a
      measure of axonal degeneration) with calf muscle mass and density, two
      complementary measures of sarcopenia. NCV and CMAP were assessed by surface
      electroneurography of the right peroneal nerve conducted in 1162 participants,
      515 men and 647 women, age 21-96 years, free of major neurological diseases.
      Cross-sectional muscle area and calf muscle density were measured using
      peripheral quantitative computerized tomography (pQCT). Both nerve and muscle
      parameters declined with age although in most cases the decline was not linear.
      In both sexes, CMAP, but not NCV, was independently and significantly associated
      with calf muscle density. These findings suggest that intrinsic changes in the
      muscle tissue are partially caused by a reduction in the number of motor axons.

PMID- 16085339
TI  - Cerebrospinal fluid tau and beta-amyloid in Alzheimer patients, disease controls
      and an age-matched random sample.
AB  - We prospectively evaluated the diagnostic accuracy of cerebrospinal fluid (CSF)
      beta-amyloid1-42 (Abeta42), -total-tau (tau) and -phosphorylated-tau181 (p
      tau181) as measured by sandwich ELISAs in the clinical routine of a community
      state hospital to discriminate between patients with Alzheimer's disease (AD),
      healthy controls (HC), non-AD-dementias, a group composed of various psychiatric
      disorders (non-AD-dementias, mental diseases) and an age-matched random sample
      (RS) (total N=219). By comparing patients with AD to HC as reference, tau
      revealed sensitivity (sens)/specificity (spec) of 88%/80%, p-tau(181) 88%/80%,
      tau/Abeta42-ratio 81%/85% and phospho-tau(181)/Abeta42-ratio 81%/78%.
      Discriminative power between HC and all dementias under investigation was
      estimated lower for tau (78%/77%) and p-tau(181) (73%/79%). Relative to patients
      with AD, ROC analysis for the RS revealed highest sens/spec for p-tau181
      (79%/77%) and p-tau181/Abeta42 ratio (78%/75%). Differentiation between AD versus
      a group made of patients with various psychiatric disorders was optimised by
      using CSF-p-tau181 (80%/77%). Under clinical routine conditions current CSF
      biomarkers show a substantial capacity to discriminate between AD and HC as
      reference and to mark off AD patients from RS and heterogeneous diagnostic groups
      composed of non-AD dementias and other psychiatric conditions. Despite a residual
      substantial overlap between the groups, we conclude that current CSF markers are
      well suited to support AD-related diagnostic procedures in every-day clinics.

PMID- 16085340
TI  - Vaccination of newborn mice induces a strong protective immune response against
      respiratory and genital challenges with Chlamydia trachomatis.
AB  - Chlamydia trachomatis infections can occur early in life and may result in long
      term sequelae. To assess the feasibility of implementing a vaccine in newborns,
      groups of 2-day-old BALB/c mice were immunized intranasally (i.n.) with 1x10(4)
      inclusion forming units (IFU) of C. trachomatis mouse pneumonitis (MoPn). As a
      control, newborn mice were sham-immunized i.n. with minimal essential medium. In
      the vaccinated animals, strong Chlamydia-specific humoral and cell-mediated
      immune responses were observed. Six weeks after immunization, mice were
      challenged with MoPn i.n. or intravaginally (i.vag.). For the i.n. challenge,
      mice were inoculated with 10(4) or 10(5)IFU of MoPn per mouse, and in the case of
      the i.vag. challenge, each animal received 10(6)IFU. By day 10 post-infection
      (p.i.), the vaccinated mice challenged i.n. with 10(4)IFU, had gained an average
      of 6.7+/-1% of their body weight. In contrast, the sham-immunized mice had lost
      14.9+/-1% of their weight (P<0.05). The mean number of IFU/lungs in the
      vaccinated animals was 800+/-300, while for the sham-immunized mice was 211+/
      49x10(6) (P<0.05). Significant differences between the Chlamydia-vaccinated and
      the sham-immunized mice were also found in the groups challenged with 10(5)IFU.
      In the mice challenged i.vag., a significant decrease in the number of mice with
      positive cultures, and the intensity and duration of vaginal shedding was noted
      in the vaccinated mice compared to the sham-immunized mice (P<0.05). In
      conclusion, these results indicate that vaccination of neonatal mice can result
      in a protective response against a subsequent pulmonary or genital challenge with
      Chlamydia.

PMID- 16085341
TI  - DNA vaccination of macaques by a full-genome SHIV plasmid that has an IL-2 gene
      and produces non-infectious virus particles.
AB  - We previously reported that a mutant full-sized plasmid DNA vaccine regime in
      macaques was effective against a homologous challenge [Akahata W, Ido E, Shimada
      T, Katsuyama K, Yamamoto H, Uesaka H, et al. DNA vaccination of macaques by a
      full genome HIV-1 plasmid which produces non-infectious virus particles. Virology
      2000;275:116-24; Akahata W, Ido E, Akiyama H, Uesaka H, Enose Y, Horiuchi R, et
      al. DNA vaccination of macaques by a full genome SHIV-1 plasmid that produces non
      infectious virus particles. J Gen Virol 2003;84:2237-44]. In this study, to
      evaluate the DNA vaccination regime against a heterologous challenge, a novel
      plasmid named pSHIV-ZF1*IL-2 was constructed. Four monkeys were intramuscularly
      and intradermally injected four times with the pSHIV-ZF1*IL-2. Vaccinated monkeys
      were intravenously challenged with a highly pathogenic, heterologous SHIV at 11
      weeks post vaccination. All the vaccinated monkeys suppressed the challenge virus
      rapidly under the detectable level by 16 weeks post challenge. One vaccinated
      monkey was protected from a loss of CD4+ T cells. These results suggest pSHIV
      ZF1*IL-2 alone seems partially effective even against a challenge with a
      heterologous, pathogenic virus.

PMID- 16085342
TI  - Process development for a Cuban cholera vaccine based on the attenuated strain
      Vibrio cholerae 638.
AB  - Genetically modified Vibrio cholerae strain 638 (biotype El Tor, serotype Ogawa)
      has previously been shown to be immunogenic in animal models and in human trials.
      Our objective in the work reported herein was to describe the process development
      methods for the production of the 638 attenuated cholera vaccine. Cell seed bank,
      culture of biomass, lyophilization and final formulation were processes were
      developed. The results show kinetics of culture that fulfils a logistical model.
      The microbiological properties, colonizing capability, immunogenicity and non
      toxigenicity of the final product were indistinguishable from the properties of
      the working seed lot. We conclude that the non-reactogenic, immunogenic and
      protective strain 638 is robust and can withstand the fermentation processes
      required for large-scale production of a vaccine.

PMID- 16085343
TI  - Magnetic resonance imaging in the diagnosis of glomus tumours of the hand.
AB  - This paper studies the sensitivity, specificity and predictive values of MRI in
      the diagnosis of glomus tumours of the hand and investigates the final diagnosis
      and outcome in cases with false positive or negative imaging tests. A total of 42
      cases with the clinical diagnosis of a glomus tumour were included in the study.
      All patients underwent MRI and the results of MRI were correlated with the final
      histological diagnosis of the excised lesion. MRI had a sensitivity of 90%, a
      specificity of 50%, a positive predictive value of 97% and a negative predictive
      value of 20%. The four cases in which the MRI was negative all proved
      histologically to be glomus tumours. All four tumours were small (2-3mm in
      diameter) and the lack of delineation of the lesions by MRI was attributed to
      their small size. Despite negative MRIs, surgical exploration identified the
      glomus tumours. Based on the results of the current study and the cost of MRI,
      the senior author has stopped ordering pre-operative MRIs in patients clinically
      diagnosed with a glomus tumour.

PMID- 16085344
TI  - Illnesses you have to fight to get: facts as forces in uncertain, emergent
      illnesses.
AB  - Chronic fatigue syndrome and multiple chemical sensitivity are two clusters of
      illnesses that are pervaded by medical, social and political uncertainty. This
      article examines how facts are talked about and experienced in struggles over
      these emergent, contested illnesses in the US. Based principally on a large
      archive of internet newsgroup postings, and also on fieldwork and on published
      debates, it finds that (1) sufferers describe their experiences of being denied
      healthcare and legitimacy through bureaucratic categories of exclusion as
      dependent upon their lack of biological facts; (2) institutions manage these
      exclusions rhetorically through exploiting the open-endedness of science to deny
      efficacy to new facts; (3) collective patient action responds by archiving the
      systematic nature of these exclusions and developing counter-tactics. The result
      is the maintenance of these very expensive struggles for all involved.

PMID- 16085345
TI  - Volunteer human subjects' understandings of their participation in a biomedical
      research experiment.
AB  - The paper focuses on how volunteer human subjects in research understand their
      own participation in experimentation. We ask how they view their own role, the
      experimental setting, and how they articulate their understanding of the
      researcher-subject relationship. The empirical basis of the study is participant
      observation and qualitative semi-structures interviews with volunteers in an
      experimental setting far removed from the more commonly studied randomised
      control trial (RCT), namely, the early stage testing of a prototype instrument
      for breast imaging. Analysis of this empirical data leads us to conclude that
      research subjects do not conform solely to one or other of the models of the
      researcher-subject relationship suggested in the literature. Rather, the
      interaction needs to be considered as a social situation which volunteer subjects
      actively negotiate in real time. They move through multiple roles and identities
      as part of the navigation through unfamiliar social territory, in order to
      establish a relationship in which they can feel socially comfortable and
      appropriately valued.

PMID- 16085346
TI  - Immunization in India 1993-1999: wealth, gender, and regional inequalities
      revisited.
AB  - Previously published evidence from the 1992-1993 Indian National Family and
      Health Survey (NFHS) on the state of childhood immunization showed the importance
      of analyzing immunization outcomes beyond national averages. Reported total
      system failure (no immunization for all) in some low performance areas suggested
      that improvements in immunization levels may come with a worsening of the
      distribution of immunization based on wealth. In this paper, using the second
      wave of the NFHS (1998-1999), we take a new snapshot of the situation and compare
      it to 1992-1993, focusing on heterogeneities between states, rural-urban
      differentials, gender differentials, and more specifically on wealth-related
      inequalities. To assess whether improvements in overall immunization rates
      (levels) were accompanied by distributional improvements, or conversely, whether
      inequalities were reduced at the expense of overall achievement, we use a
      recently developed methodology to calculate an inequality-adjusted achievement
      index that captures performance both in terms of efficiency (change in levels)
      and equity (distribution by wealth quintiles) for each of the 17 largest Indian
      states. Comparing 1992-1993 to 1998-1999 achievements using different degrees of
      "inequality aversion" provides no evidence that distributional improvements occur
      at the expense of overall performance.

PMID- 16085347
TI  - Caffeic acid phenethyl ester (CAPE) prevents transformation of human cells by
      arsenite (As) and suppresses growth of As-transformed cells.
AB  - Recent evidence suggests that inflammatory cytokines and growth factors
      contribute to arsenite (As)-induced human carcinogenesis. We investigated the
      expression of inflammatory cytokine mRNAs during the transformation process
      induced by chronic As exposure in non-tumorigenic human osteogenic sarcoma (N
      HOS) cells using gene arrays, and results were confirmed by RT-PCR and protein
      arrays. Caffeic acid phenethyl ester (CAPE), a naturally occurring
      immunomodulating agent, was used to evaluate the role of inflammatory factors in
      the process of As-mediated N-HOS cell transformation and in As-transformed HOS
      (AsT-HOS) cells. We found that an 8-week continuous exposure of N-HOS to 0.3
      microM arsenite resulted in HOS cell transformation. That exposure also caused
      substantial decreases in inflammatory cytokine mRNAs, such as interleukin (IL) IL
      1alpha, IL-2, IL-8, IL-18, MCP-1, TGF-beta2, and TNF-alpha, while it increased c
      jun mRNA in a time-dependent manner. Co-incubation of N-HOS with As and CAPE (0.5
      2.5 microM) prevented As-mediated declines in cytokine mRNAs in the co-treated
      cells, as well as their transformation to anchorage independence, while it caused
      decreases in c-jun mRNA. CAPE (up to 10 microM) had no effect on growth of N-HOS
      cells. However, CAPE (1-10 microM) treatment of AsT-HOS cells inhibited cell
      growth, induced cell cycle G2/M arrest, and triggered apoptosis, accompanied by
      changes in cytokine gene expression, as well as decreases in cyclin B1 and cdc2
      abundance. Resveratrol (RV) and (-)(.) epigallocatechin gallate (EGCG),
      preventive agents present in grapes and green tea, respectively, induced similar
      changes in AsT-HOS cell growth but required much higher doses than CAPE to cause
      50% growth arrest (<2.5 microM CAPE versus 25 microM RV or 50 microM EGCG).
      Overall, our findings suggest that inflammatory cytokines play an important role
      in the suppressive effects of CAPE on As-induced cell transformation and in the
      selective cytotoxicity of CAPE to As-transformed HOS cells.

PMID- 16085348
TI  - dl-alpha-lipoic acid ameliorates cyclophosphamide induced cardiac mitochondrial
      injury.
AB  - Mitochondria play a central role in heart metabolism and function. Administration
      of antineoplastic drug cyclophosphamide (CP) adversely affects the heart
      mitochondria which may result in cardiotoxicity. The present study is aimed at
      evaluating the role of lipoic acid (LA) in CP induced myocardial injury. Male
      albino rats of Wistar strain were used for the study. CP was administered as a
      single intraperitoneal injection (200 mg/kg BW). A decrease in the activities of
      TCA cycle enzymes such as succinate dehydrogenase, malate dehydrogenase and
      isocitrate dehydrogenase was noted in CP treated rats. Simultaneously there was a
      decrease in the activities of mitochondrial complexes of electron transport
      chain. Decrease in the activities of these enzymes suggests a loss in
      mitochondrial function and integrity. Ultrastuctural observations were also in
      agreement with the above abnormal changes. Loss of myofilaments and damage of
      mitochondrial cristae revealed the cytotoxic effect of CP. The supplementation of
      LA (25 mg/kg BW) restored the above abnormalities to near normalcy. The study
      brings out the importance of LA in improving the mitochondrial function in
      cardiac cells after CP administration.

PMID- 16085349
TI  - Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level
      in plasma and brain of ischemic stroke model.
AB  - We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the
      levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression
      of nuclear factor kappa B (NF-kappaB) during experimental focal cerebral
      ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were
      administered to 80 Sprague-Dawley rats [3-AB group; 5 rats for plasma sampling,
      35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40,
      respectively), respectively, 10 min before the occlusion of the left middle
      cerebral artery (MCAo) for 2 h. Infarct volume was measured by TTC staining, the
      serial levels of plasma and brain MMP-9 were measured by zymography just before
      and 2, 4, 8, 24, 48, and 72 h after MCAo, brain NF-kappaB activity was determined
      by Western blotting, and neutrophil infiltration was evaluated by assessing
      myeloperoxidase activity. Compared with control group, the levels of plasma and
      brain MMP-9, brain NF-kappaB, and MPO activities were significantly reduced in 3
      AB group at each time point (p<0.05). Plasma MMP-9 increased maximally at 4h and
      then decreased rapidly, brain MMP-9 increased maximally at 24 h and persisted
      until 72 h, and NF-kappaB increased maximally at 24h and then decreased slowly in
      both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF
      kappaB and the infiltration of neutrophils in ischemic stroke.

PMID- 16085350
TI  - The optimisation of the initial viscosity of an encapsulated glass-ionomer
      restorative following different mechanical mixing regimes.
AB  - OBJECTIVES: An optimisation of the mixing ratio of an encapsulated glass-ionomer
      restorative in terms of compressive strength, working characteristics and pore
      distribution following mechanical mixing with different mixing machines was
      undertaken. METHODS: Mean compressive fracture strengths, standard deviations and
      associated Weibull Moduli (m) were determined from series of 30 encapsulated
      specimens with varying powder/liquid mixing ratios. Working characteristics were
      assessed using an oscillating rheometer and scanning electron microscopy and
      image analysis was used to investigate the influence of the mixing ratios and
      mixing regime on the pore distribution. RESULTS: Cement mixing regime or reducing
      the powder/liquid mixing ratio did not have any significant influence on the
      compressive strength. Utilising the one-way ANOVA and Tukey test comparisons at
      P<0.05 the cement manipulation regime significantly increased the compressive
      strength on increasing the powder content of the capsule by 10% (G110) when a
      combination of rotational and centrifugal action rather than vibration were
      employed. Utilising a Rotomix at a powder content of G110 was beneficial in
      reducing porosity levels within the restorative investigated compared with a
      conventional mixing machine. Increasing the powder content reduced the working
      characteristics regardless of the mixing regime. SIGNIFICANCE: The increased
      reliability of encapsulated restoratives reported in the literature following
      mixing with a combination of rotational and centrifugal compared with vibrational
      action was only evident when the powder content of the restorative under
      investigation was increased by 10%. The finding suggests that the initial
      viscosity of the cement mass of the Ketac Fil Plus Aplicap as supplied by the
      manufacturer may not have been optimised.

PMID- 16085351
TI  - A novel butyrylcholinesterase from serum of Leporinus macrocephalus, a
      Neotropical fish.
AB  - We show here that serum of piaussu, a Neotropical characin fish, has the highest
      butyrylcholinesterase activity so far described for humans and fish. To clarify
      whether this cholinesterase could protect piaussu against anticholinesterase
      pesticides by scavenging organophosphates, we purified it 1700-fold, with a yield
      of 80%. Augmenting concentrations (from 0.01 to 20 mM) of butyrylthiocholine
      activated it. The pure enzyme was highly inhibited by chlorpyriphos-oxon
      (ki=10,434x10(6) M-1 min-1) and by the specific butyrylcholinesterase inhibitor,
      isoOMPA (ki=45.7x10(6) M-1 min-1). Electrophoresis of total serum and 2-D
      electrophoresis of the purified cholinesterase showed that some enzyme molecules
      could circulate in piaussu serum as heterogeneously glycosylated dimers. The
      enzyme's N-terminal sequence was similar to sequences found for
      butyrylcholinesterase from sera of other vertebrates. Altogether, our data
      present a novel butyrylcholinesterase with the potential of protecting a fish
      from poisoning by organophosphates.

PMID- 16085352
TI  - Resolution of the structure of the allergenic and antifungal banana fruit
      thaumatin-like protein at 1.7-A.
AB  - The structure of a thaumatin-like protein from banana (Musa acuminata) fruit, an
      allergen with antifungal properties, was solved at 1.7-A-resolution, by X-ray
      crystallography. Though the banana protein exhibits a very similar overall fold
      as thaumatin it markedly differs from the sweet-tasting protein by the presence
      of a surface exposed electronegative cleft. Due to the presence of this
      electronegative cleft, the banana thaumatin-like protein (Ban-TLP) acquires a
      strong (local) electronegative character that eventually explains the observed
      antifungal activity. Our structural analysis also revealed the presence of
      conserved residues of exposed epitopic determinants that are presumably
      responsible for the allergenic properties of banana fruit towards susceptible
      individuals, and provided evidence that the Ban-TLP shares some structurally
      highly conserved IgE-binding epitopes with thaumatin-like proteins from fruits or
      pollen from other plants. In addition, some overlap was detected between the
      predicted IgE-binding epitopes of the Ban-TLP and IgE-binding epitopes previously
      identified in the mountain cedar Jun a 3 TLP aeroallergen. The presence of these
      common epitopes offers a molecular basis for the cross-reactivity between
      aeroallergens and fruit allergens.

PMID- 16085353
TI  - Traumatic haemo-pneumothorax or intubation of right main bronchus?

PMID- 16085354
TI  - Neural regulation of bone and the skeletal effects of serotonin (5
      hydroxytryptamine).
AB  - There is increasing evidence for a contribution of the neural system to the
      regulation of bone metabolism. The skeleton is richly innervated by both
      sympathetic and sensory neurons. While these nerves serve sensory and vascular
      functions, they are also being found to influence bone cell activities. The most
      convincing evidence for this has been provided by studies into the skeletal
      effects of the hormone leptin, which has been shown to centrally regulate bone
      mass, and through studies into the skeletal effects of hypothalamic neuropeptide
      Y2 and Y4 receptors. This paper discusses recent evidence for the neural
      regulation of bone metabolism and, in particular, the potential role of the
      neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Recent studies have
      demonstrated the presence of functional pathways in bone for both responding to
      and regulating the uptake of 5-HT. This is of high clinical relevance given the
      role of the serotonergic system in affective disorders, and the wide use of
      pharmacological agents that target the 5-HT system to manage these disorders.
      Initial data suggest that exposure to these agents at different stages during the
      lifespan may have significant effects on the skeleton.

PMID- 16085355
TI  - Lack of correlation between leptin receptor expression and PI3-K/Akt signaling
      pathway proteins immunostaining in endometrioid-type endometrial carcinomas.
AB  - A number of studies published recently focused on the putative role of leptin in
      the pathogenesis of various primary human malignancies. Current study was aimed
      at investigating ObR, PI3-kinase, phospho-Akt kinase and PTEN proteins expression
      in forty-five primary human endometrioid-type endometrial carcinomas (EC). ObR
      immunostaining was detected in 21 of 45 (47%) ECs, presented in almost 60% of
      well- and moderately-differentiated tumors compared to only 17% of poorly
      differentiated neoplasms (P<0.05). Semi-quantitative histological score (H-score)
      ObR values were inversely correlated with patients' body mass index (R=-0.35;
      P=0.019). ObR expression was significantly higher in normal weight compared to
      overweight and obese patients (P=0.024). All slides displayed intense PI3-kinase
      immunoreactivity, whereas phospho-Akt kinase expression was reported in 96% (43
      out of 45) cases. Fifteen (33%) ECs were negative for PTEN expression, nine (20%)
      showed heterogeneous immunostaining pattern, whereas 21 (47%) were PTEN-positive.
      There was a trend towards a higher phospho-Akt kinase intensity immunostaining in
      PTEN-negative compared to PTEN-positive cases, but the difference was not
      significant. There was no significant association between each PI3-K/Akt
      signaling pathway proteins immunostaining in endometrioid-type ECs. In
      conclusion, ObR expression is associated with histological grading and the weight
      of women affected by EC. The components of PI3-K/Akt kinase signaling pathway are
      expressed in most of the primary endometrioid-type endometrial neoplasms.

PMID- 16085356
TI  - The roles of Chk 1 and Chk 2 in hypoxia and reoxygenation.
AB  - Both Chk 1 and Chk 2 are critically important checkpoint kinases. Chk 1 is an
      essential gene that is required for normal cell division and Chk 2 has been found
      to be mutated in an ever-growing list of human malignancies. Our recent studies
      indicate that both Chk 1 and Chk 2 have roles to play in the physiological stress
      of hypoxia/reoxygenation. Loss or inhibition of either kinase sensitizes cells to
      hypoxia/reoxygenation indicating that either or both could represent significant
      therapeutic targets.

PMID- 16085357
TI  - Elevated phosphorylation of Chk1 and decreased phosphorylation of Chk2 are
      associated with abrogation of G2/M checkpoint control during transformation of
      Syrian hamster embryo (SHE) cells by Malachite green.
AB  - Malachite green (MG), consisting of green crystals with a metallic lustre, is
      highly soluble in water, cytotoxic to various mammalian cells and also acts as a
      liver tumor promoter. In view of its industrial importance and possible exposure
      to human beings, MG poses a potential environmental health hazard. We have
      earlier reported the malignant transformation of Syrian hamster embryo (SHE)
      cells in primary culture by MG. In this study, we have studied the ability of MG
      to cause DNA damage, cell cycle arrest in mimosine synchronised and the possible
      roles of Chk1, Chk2, Cdc2, Cdc25C, 14-3-3 and Cyclin B1 in control and MG
      transformed SHE cells in order to understand the differential mechanisms
      associated with G2/M checkpoint control. Exposure of MG to control and
      transformed cells causes DNA damage. Flow cytometric analysis of mimosine
      synchronised cells when exposed to MG showed an increase of G2/M phase in control
      cells whereas no such accumulation of cells at the G2/M phase was observed in
      response to MG in transformed cells. Western blots of phosphoactive forms of Chk1
      and Chk2 cells showed opposing levels. Control cells treated with MG showed a
      decrease in Chk1 and increase in Chk2, whereas the transformed cells treated with
      MG showed an increase in Chk1 and decrease in Chk2. Also a decrease in Cdc25C, 14
      3-3 and Cyclin B1 was observed in MG treated transformed cells, whereas MG
      treated control cells showed elevated levels. Stabilization of the proteins seems
      to be the possible mechanism. The present study indicates elevated
      phosphorylation of Chk1 and decreased phosphorylation of Chk2 and decreased
      levels of Cyclin B1 are the critical changes associated with abrogation of G2/M
      checkpoint control during transformation of SHE cells by MG.

PMID- 16085358
TI  - Degradation of 17beta-estradiol and bisphenol A in aqueous medium by using ozone
      and ozone/UV techniques.
AB  - Decomposition and complete degradation of two endocrine disrupters, namely 17beta
      estradiol (E2) and bisphenol A (BPA) in aqueous medium by using ozone (O3) only
      and O3/UV advanced oxidation techniques (AOT) has been studied. The efficiency of
      the O3 systems used were determined based on the initial conversion and complete
      degradation of the substrates. Within the limits of the O3 dosages used, coupling
      of UV decreased the O3 consumption by 22.5% in converting the same amount of E2.
      Also the time to convert the same amount of E2 was considerably decreased. It was
      observed that there is no significant difference in O3 amount consumed for
      complete conversion of BPA by O3 and O3/UV systems. However, when O3 dosage
      decreased the amount of BPA conversion exhibits significant differences between
      two processes. The intermediate products formed during the oxidation of E2 were
      determined to be formed by oxidation of aromatic side of E2 with O3/*OH radical.

PMID- 16085359
TI  - Effects of inactivation of serotonergic neurons of the median raphe nucleus on
      learning and performance of contextual fear conditioning.
AB  - Several studies have shown that the median raphe nucleus (MRN) is involved in
      anxiety. However, no study assessed the role of 5-HT mechanisms of MRN in both
      freezing and fear-potentiated startle (FPS) within a single form of conditioned
      learning. In this work we examined the effects of neurotoxic lesions of the MRN
      with NMDA on freezing and FPS of rats submitted to a contextual fear conditioning
      paradigm, in which they were tested in the same chamber where they received foot
      shocks 24 h before. Compared to controls NMDA-injected rats showed a reduction of
      freezing and FPS in response to contextual cues. Next, we examined the effects of
      stimulation of 5-HT1A somatodendritic autoreceptors of the MRN with local
      injections of 8-OH-DPAT either before training or testing sessions conducted 2 or
      24 h post-conditioning. Pre-training injections of 8-OH-DPAT intra-MRN reduced
      both freezing and FPS whereas post-training injections reduced only freezing to
      the aversive context without changing the FPS. Thus, freezing is easily disrupted
      by post-training MRN injections of 8-OH-DPAT while memory for FPS remained
      unchanged. It is proposed that the consolidation of contextual conditioned fear
      promoting freezing takes place through a slow mechanism of transference of
      information through 5-HT mechanisms of the MRN-hippocampus pathway. On the other
      hand, a rapid fear conditioning process operates for FPS, probably through other
      pathways.

PMID- 16085360
TI  - C3a expressed in the central nervous system protects against LPS-induced shock.
AB  - Complement is implicated in the pathogenesis of inflammatory disorders of the
      central nervous system (CNS), like multiple sclerosis, Alzheimer's disease, and
      trauma. The anaphylatoxins C3a and C5a are thought to be the major contributors
      to complement-mediated inflammation in the CNS, likely mediating their effects
      via their ability to attract and activate leukocytes and common capacity to
      augment inflammation. For example, in experimental autoimmune encephalomyelitis,
      the animal model of multiple sclerosis, CNS-specific expression of C3a in
      C3a/GFAP transgenic mice renders them prone to massive cellular infiltration of
      the CNS and increases their mortality. In contrast, other studies have suggested
      that C3a can function in an anti-inflammatory fashion in the CNS, by inducing
      neurotrophin production and preventing NMDA-mediated neurotoxicity. To further
      investigate the seemingly paradoxical role of C3a in acute inflammation of the
      brain, we studied the pathogenesis of endotoxin shock in C3a/GFAP transgenic, C3a
      receptor-deficient (C3aR-/-) and C3a/GFAPxC3aR-/- mutant mice. Here we report
      that C3a/GFAP mice were significantly more resistant to endotoxin-induced
      lethality than wild-type and C3aR-/- mice. Surprisingly, C3a/GFAPxC3aR-/- hybrids
      were also significantly protected, indicating that C3a exerts its protective anti
      inflammatory effect either directly or via an as yet unidentified non-canonical
      C3aR.

PMID- 16085361
TI  - Modulation of delayed rectifier potassium channels by alpha1-adrenergic
      activation via protein kinase C zeta and p62 in PC12 cells.
AB  - When PC12 cells are exposed to nerve growth factor (NGF), they extend neurites
      and express autonomic ganglion cell properties. We have previously shown that NGF
      is capable of inducing p62 expression, enabling the formation of the protein
      kinase C zeta (PKCzeta)-p62-Kvbeta (beta-subunit of delayed rectifier K+ channel)
      complex, a Kv channel-modulating complex. The formation of this complex results
      in the shifting of the Kv channel activation curve to the left via PKCzeta
      activity. During the experiments, we noted that PC12 cells in a high-density
      culture exhibited a Kv channel activation curve shift similar to that observed in
      the NGF-treated cells. Therefore, we hypothesized that catecholamines released
      from PC12 cells may induce p62 expression. In order to test this idea, cells in a
      low-density culture were treated for 24h with norepinephrine (NE). In these
      cells, we noted a leftward shift of the activation curve. The presence of the
      alpha1-adrenergic antagonist specifically prevented the effects of NE. Pre
      treatment of the low-density cells with alpha1-agonists induced changes similar
      to those associated with NE, confirming that NE modulates Kv channels via the
      alpha1-adrenergic receptor. NE's effects were blocked by treatment with PKCzeta
      specific inhibitors. Using Western blotting, we observed increased levels of p62
      expression in both the high-density cells and the NE-treated low-density cells.
      These results suggest that locally secreted NE induces an increase in p62
      expression, and also exerts a modulatory effect on Kv channels via the PKCzeta
      p62-Kvbeta channel modulating complex.

PMID- 16085362
TI  - Lack of interaction between orexinergic and alpha2-adrenergic neuronal systems in
      rat cerebrocortical slices.
AB  - Orexinergic and norepinephrinergic alpha2-adrenoceptor expressing neurons
      contribute to the regulation of the sleep-wakefulness cycle. In the present
      study, we have examined a possible interaction between orexinergic and alpha2
      adrenergic systems in orexin-A (100 nM)- and K+ (25 mM)-evoked norepinephrine
      release from slices of rat cerebrocortex. In this tissue norepinephrinergic
      neurons are predominantly innervated via the locus coeruleus. Clonidine
      concentration-dependently inhibited K+-evoked norepinephrine release with pIC50
      (Imax) of 6.44+/-0.38 (48.8+/-6.9%). A selective orexin-1 receptor antagonist, SB
      334867 was ineffective. SB-334867 concentration-dependently inhibited orexin A
      evoked norepinephrine release with pIC50 (Imax) of 6.05+/-0.14 (86.4+/-5.4%);
      clonidine (alpha2-agonist) was ineffective. In contrast, yohimbine reversed the
      inhibitory effects of clonidine (1 microM) on K+-evoked norepinephrine release
      with pIC50 (Imax) of 6.50+/-0.34 (77.6+/-10.9%); orexin A was ineffective. The
      present data suggest a lack of interaction between orexinergic and alpha2
      adrenergic neurons in rat cerebral cortex.

PMID- 16085363
TI  - Cocaine alters catalase activity in prefrontal cortex and striatum of mice.
AB  - Catalase is one of the enzymes that convert hydrogen peroxide (H2O2) to H2O
      presenting a protective role against free radicals. In this study, catalase
      activity was determined in homogenates of striatum (ST) and prefrontal cortex
      (PFC) in order to examine the participation of oxidative stress (OS) on cocaine
      actions in mice brain. Male Swiss mice were injected (i.p.) with cocaine at low
      (10 and 30 mg/kg) and high doses (90 mg/kg), and observed for 1 h. After cocaine
      overdose (90 mg/kg) some animals presented only status epilepticus (SE) while
      others died after seizures. These animals were dissected and divided in two
      groups, SE and death. Catalase activity was also determined after pretreatment
      with the anticonvulsant drug, diazepam, alone or injected before cocaine 90
      mg/kg, and after seizures induced by a high dose of bupropion, a known inhibitor
      of NE and DA reuptake used for comparison. Results showed a decrease in catalase
      activity of the PFC and ST after SE and death induced by cocaine and bupropion
      overdoses. Cocaine at low doses decreased the enzyme activity only in ST.
      Diazepam treatment alone and before cocaine overdose did not interfere with
      catalase activity. This reduction in catalase activity may reflect an increase in
      H2O2 content in PFC and ST. Previous data reports that H2O2 inhibits dopamine
      transporter activity, suggesting that the decrease in catalase activity may
      potentiate the toxic mechanism of drugs that inhibit monoamines reuptake. As far
      as we know, this is the first report showing an involvement of OS in the
      cocaine's central mechanism of action.

PMID- 16085364
TI  - Six-month prophylactic efficacy of moxidectin sustained release (SR) injectable
      for dogs against experimental heartworm infection in growing puppies.
AB  - The purpose of this study was to assess the efficacy of moxidectin sustained
      release injectable for dogs (moxidectin SR, Fort Dodge Animal Health) in
      protecting growing puppies from experimental infection with the heartworm,
      Dirofilaria immitis, six months after treatment. The study involved 27 puppies,
      approximately 12 weeks of age at the beginning of the study, with nine puppies in
      each of three size classes. The small breed class included eight Pekingese and
      one purpose-bred small breed mongrel; the medium breed class included nine
      purpose-bred mongrels, and the large breed class included nine puppies with an
      anticipated adult weight >or=30-35 kg. Both genders were included with no attempt
      made to have equal numbers of male and female puppies. Puppies were blocked by
      weight within each size class and randomly assigned to three treatment groups of
      nine dogs. On Day 0, pups in two groups were injected subcutaneously with
      moxidectin SR, dosed to deliver 0.17 mg moxidectin/kg b.w. The third group was
      injected with sterile saline. Personnel making observations were blinded to the
      treatment status of the animals. Following treatment, puppies were observed for
      signs of adverse local and systemic reactions. Puppy weights and serum moxidectin
      levels were also monitored. On Day 180, puppies in all treatment groups were
      inoculated subcutaneously with 50 third-stage larvae of D. immitis. On Days 348
      and 349, puppies were euthanatized and necropsied. Hearts and lungs were examined
      for adult heartworms. All animals in the saline control group were infected with
      an arithmetic mean of 39.22 adult heartworms each. Seventeen of 18 dogs in the
      moxidectin SR-treated groups were uninfected. One treated puppy was infected with
      a single adult heartworm. This infected individual was from the large breed size
      class and had the second highest percent increase in body weight. Based on
      arithmetic means, the heartworm recovery from all treated puppies represents a
      99.86% reduction relative to the saline control. There were no adverse local or
      systemic reactions to treatment in any animal.

PMID- 16085365
TI  - Interaction between copper oxide wire particles and Duddingtonia flagrans in
      lambs.
AB  - An experiment was completed to determine if copper oxide wire particles (COWP)
      had any effect on the activity of the nematode-trapping fungus Duddingtonia
      flagrans in growing lambs. COWP has been used recently as a dewormer in small
      ruminants because of nematode resistance to anthelmintics. D. flagrans has been
      used to control free-living stages of parasitic nematodes in livestock. Katahdin
      and Dorper lambs, 4 months of age, were administered no or 4 g COWP (n=24/dose)
      in early October 2003. Haemonchus contortus was the predominant gastrointestinal
      parasite during the trial, which was acquired naturally from pasture. Half the
      lambs from each COWP group were supplemented with corn/soybean meal with or
      without D. flagrans for 35 days. Fecal egg counts (FEC) and packed cell volume
      (PCV) were determined weekly between days 0 (day of COWP administration) and 35.
      Feces from lambs in each treatment group were pooled and three replicates per
      group were cultured for 14 days at room temperature. Larvae (L3) were identified
      and counted per gram of feces cultured. Treatment with COWP was effective in
      decreasing FEC, which remained low compared with FEC from lambs not treated with
      COWP. This led to an increase in PCV in these lambs (COWP x day, P<0.001). Number
      of larvae was decreased in feces from lambs treated with COWP and D. flagrans
      between days 14 and 35 compared to the other groups of lambs (COWP x D. flagrans
      x day, P<0.003). Percentage of larvae identified as H. contortus decreased in
      feces collected from lambs treated with COWP and D. flagrans between days 14 and
      28 compared with other treatments (COWP x D. flagrans x day, P<0.05). Other
      trichostrongyles were present and remained less than 7% in feces collected from
      control lambs. There was no adverse effect of COWP on the ability of D. flagrans
      to trap residual larvae after COWP treatment. With fewer eggs being excreted due
      to the effect of copper on H. contortus, and the additional larval reducing
      effect exerted by the nematode destroying fungus D. flagrans, the expected result
      would be a much lower larval challenge on pasture when these two tools are used
      together in a sustainable control strategy.

PMID- 16085366
TI  - Changes in HIV risk behaviors among patients receiving combined pharmacological
      and behavioral interventions for heroin and cocaine dependence.
AB  - Cocaine use is associated with injecting and sexual HIV risk behaviors. This
      study was a randomized controlled trial of behavioral interventions for cocaine
      dependence and HIV risk behaviors among dually (cocaine and heroin) dependent
      outpatients. Methadone maintenance was augmented with cognitive-behavioral
      therapy (CBT), contingency management (CM), both (CBT+CM), or neither. The study
      sample (n=81) was 52% female, 70% African American, and 37.9+/-7.0 years old.
      Proportions reporting HIV risk behaviors at intake were: 96.3% (78/81) injection
      drug use, 56.8% (46/81) sharing needles, 30.9% (25/81) unprotected sex, 28.4%
      (23/81) trading sex for money or drugs. Proportions who no longer reported
      behaviors at study exit were: 51.3% (40/78) injection drug use, 91.3% (42/46)
      sharing needles, 88% (22/25) unprotected sex, 91.3% (21/23) trading sex for money
      or drugs. Participants receiving CBT+CM were more likely to report cessation of
      unprotected sex relative to control (OR=5.44, 95% CI 1.14-26.0, p=0.034) but this
      effect was no longer significant after adjusting for drug-negative urines. These
      results suggest broad beneficial effects of methadone maintenance augmented with
      behavioral interventions for reducing HIV risk behaviors.

PMID- 16085367
TI  - Add Alzheimer's to the list of sleep apnea consequences.

PMID- 16085368
TI  - Do tissue levels of autoantigenic aminoacyl-tRNA synthetase predict clinical
      disease?
AB  - The etiologies of most autoimmune diseases are not completely understood.
      Aminoacyl-tRNA synthetases (AARS) are a family of heterogenous enzymes
      responsible for protein synthesis and whose secondary functions include a role in
      autoimmune myositis. A subset of patients with idiopathic inflammatory myopathies
      demonstrate autoantibody against specific cytoplasmic AARS and the human
      asparaginyl-tRNA synthetase (AsnRS) has been shown to be a potent chemokine that
      interacts with CCR3 chemokine receptors. One way in which a chemotactic
      cytoplasmic enzyme might contribute to tissue inflammation is if it were abundant
      in a specific injured tissue and thereby released to the microenvironment at
      times of cellular damage. To test this hypothesis, the relative levels of AsnRS
      mRNA were studied in six human tissues. A 1.6 kbF RNA probe identified highly
      variable levels of the corresponding mRNA in Northern blot analysis of human
      lung, brain, heart, skeletal muscle, pancreas and liver. The highest levels of
      signal were noted in muscle and pancreas. Polyclonal antibody raised against
      recombinant human AsnRS identified abundant antigenic material in the pancreas,
      in particular in islet cells. Thus, the local abundance of an endogenous pro
      inflammatory autoantigen may provide one explanation for perpetuation or
      exacerbation of tissue specific immune-mediated pathologies.

PMID- 16085369
TI  - Characterization of the IgA1 protease from the Brazilian purpuric fever strain
      F3031 of Haemophilus influenzae biogroup aegyptius.
AB  - Brazilian purpuric fever is a severe vascular disease caused by an invasive clone
      of Haemophilus influenzae biogroup aegyptius, which normally causes self-limiting
      eye infections. A previous genome subtraction procedure resulted in the isolation
      of a DNA fragment, which encodes a putative IgA1 protease, specific to the F3031
      Brazilian purpuric fever type strain. Cloning and sequencing of the entire F3031
      iga1 gene showed that the subtracted DNA fragment encompasses the iga1 region
      encoding the active site and the cleavage specificity determinant of the protein,
      which are different from the cognate regions of the proteases produced by other
      H. influenzae strains. Western and IgA cleavage assays together with clustering
      analysis showed that the F3031 IgA1 protease is most similar to the type 2
      proteases produced by H. influenzae type c and e strains. Analysis of the
      promoter region of the F3031 iga1 gene revealed the presence of Fur binding
      sites. However, real-time PCR analysis and transcriptional fusion assays showed
      that the expression of iga1 is not regulated by iron or hemin under the
      conditions tested.

PMID- 16085370
TI  - Methanotrophic populations in estuarine sediment from Newport Bay, California.
AB  - Methanotrophic populations have been studied in Newport Bay estuary, Southern
      California. Environmental clone banks were generated for 16S rRNA genes specific
      to methanotrophs and for a diagnostic functional gene, pmoA, encoding a conserved
      subunit of the particulate methane monooxygenase. These clone banks contained
      sequences specific to types I and II methanotrophs typically found in aquatic
      environments including freshwater lake and soda lake sediments, aquifers and rice
      paddies. However, a group of clones that were divergent (93% identity) from known
      methanotrophic 16S rRNA genes but represented in 16S rRNA gene libraries from
      other aquatic environments were detected. A group of pmoA sequences divergent
      (83% identity) from extant methanotrophs and not previously represented in any
      environmental clone libraries, were also detected. It is concluded that this
      environment contains significant methanotroph diversity and that some of these
      may represent novel groups of methanotrophic bacteria.

PMID- 16085371
TI  - Synergistic biofilm formation by Treponema denticola and Porphyromonas
      gingivalis.
AB  - Biofilm formation is an important step in the etiology of periodontal diseases.
      In this study, in vitro biofilm formation by Treponema denticola and
      Porphyromonas gingivalis 381 displayed synergistic effects. Confocal microscopy
      demonstrated that P. gingivalis attaches to the substratum first as a primary
      colonizer followed by coaggregation with T. denticola to form a mixed biofilm.
      The T. denticola flagella mutant as well as the cytoplasmic filament mutant were
      shown to be essential for biofilm formation as well as coaggregation with P.
      gingivalis. The major fimbriae and Arg-gingipain B of P. gingivalis also play
      important roles in biofilm formation with T. denticola.

PMID- 16085372
TI  - 2-micron circle plasmids do not reduce yeast life span.
AB  - Extrachromosomal rDNA circles (ERCs) and recombinant origin-containing plasmids
      (ARS-plasmids) are thought to reduce replicative life span in the budding yeast
      Saccharomyces cerevisiae due to their accumulation in yeast cells by an
      asymmetric inheritance process known as mother cell bias. Most commonly used
      laboratory yeast strains contain the naturally occurring, high copy number 2
      micron circle plasmid. 2-micron plasmids are known to exhibit stable mitotic
      inheritance, unlike ARS-plasmids and ERCs, but the fidelity of inheritance during
      replicative aging and cell senescence has not been studied. This raises the
      question: do 2-micron circles reduce replicative life span? To address this
      question we have used a convenient method to cure laboratory yeast strains of the
      2-micron plasmid. We find no difference in the replicative life spans of
      otherwise isogenic cir+ and cir0 strains, with and without the 2-micron plasmid.
      Consistent with this, we find that 2-micron circles do not accumulate in old
      yeast cells. These findings indicate that naturally occurring levels of 2-micron
      plasmids do not adversely affect life span, and that accumulation due to
      asymmetric inheritance is required for reduction of replicative life span by DNA
      episomes.

PMID- 16085373
TI  - Endocrine and metabolic programming during intrauterine development.
AB  - In humans, low birth weight is associated with an increased risk of metabolic
      dysfunction in adult life. Many of these metabolic disorders have an endocrine
      origin and are accompanied by abnormal hormone concentrations. This has led to
      the hypothesis that adult metabolic disease arises in utero as a result of
      programming of key endocrine systems during suboptimal intrauterine conditions
      associated with fetal growth retardation. This review examines the experimental
      evidence for prenatal endocrine programming with particular emphasis on endocrine
      axes involved in growth and metabolism, namely, the hypothalamic-pituitary
      adrenal axis, the endocrine pancreas and the somatotrophic axis. It also
      considers how changes in these endocrine systems contribute to the programming of
      metabolism in later life.

PMID- 16085374
TI  - Pharmacokinetics of antivirals in neonate.
AB  - BACKGROUND: About 1000 neonates with HIV infection are born every day worldwide.
      The antiviral therapy for newborn infants is a real necessity. Pharmacokinetics
      is an important contribution to therapy and no review has been published on the
      pharmacokinetics of antivirals in neonates up to now. AIMS: This article provides
      a review on the pharmacokinetics of antivirals in the neonate. The
      pharmacokinetic parameters in the neonate are compared with those of the adult,
      and when possible, the pharmacokinetic parameters were compared in neonates of
      different ages. RESULTS: Zidovudine is the antiviral with the largest amount of
      information on its pharmacokinetics. The clearance (Cl; l/h/kg) of zidovudine is
      0.15 (premature), 0.34 (1 day), 0.69 (7 days), 0.65 (< or =14 days), 1.14 (>14
      days) and 1.56 (adult). t(1/2) (h) of zidovudine is 7.2 (premature), 4.2 (1 day),
      4.0 (7 days), 3.1 (< or =14 days), 1.9 (>14 days) and 1.1 (adult). Zidovudine is
      mainly eliminated by conjugation with glucuronic acid and glucuronosyl
      transferase develops postnatally. Cl of lamivudine is 0.19 (1 day), 0.32 (7 days)
      and 0.30 (adult) and the Cl (l/h/m2) of didanosine is 65 (1 day) and 271 (7
      days). A greater volume of distribution (Vd) has been observed in the neonate
      compared with the adult for nelfinavir, nevirapine and pleconaril. CONCLUSIONS:
      The pharmacokinetic parameters of antivirals differ in the neonate and in the
      adult. The Cl is reduced and t(1/2) is increased in the neonate compared with the
      adult for zidovudine, lamivudine and ganciclovir. t(max) is generally greater in
      the neonate than in the adult due to reduced absorption rate in the neonate. The
      Vd of nelfinavir, nevirapine and pleconaril is greater in the newborn than in the
      adult. The neonate is a developing organism and the pharmacokinetic parameters of
      antivirals vary during the first weeks of life.

PMID- 16085375
TI  - Evidence of genetic regulation of fetal longitudinal growth.
AB  - BACKGROUND: Genetic as well as environmental factors are important determinants
      of fetal growth but there have been few studies of the influence of paternal
      factors on fetal growth. AIM: To study the influence of paternal anthropometry on
      detailed measurements of offspring at birth. DESIGN: A prospective cohort study
      involving biochemistry, and anthropometry, of mothers and fathers at 28 weeks
      gestation, and detailed anthropometry of children within 24 h of birth. SUBJECTS:
      567 White Caucasian singleton, non-diabetic, full term pregnancies recruited from
      central Exeter, UK. RESULTS: Paternal height, but not paternal BMI, was
      correlated with birth weight (r = 0.19) and with birth length (r = 0.33). This
      was independent of potential confounders and maternal height. All measurements of
      fetal skeletal growth including crown-rump, knee-heel and head circumference were
      associated with paternal height. Maternal height showed similar correlations with
      birth weight (r = 0.18) and birth length (r = 0.26). Maternal BMI was correlated
      with birth weight (r = 0.27) and birth length (r = 0.15). In a multifactorial
      analysis 38% of the variance in fetal height could be explained by gestation,
      sex, paternal height, maternal height, maternal glucose, maternal BMI, parity and
      maternal smoking. CONCLUSION: Paternal height has an independent influence on
      size at birth. This predominantly influences length and skeletal growth of the
      baby. In contrast to maternal obesity the degree of paternal obesity does not
      influence birth weight. This work suggests that there is genetic regulation of
      skeletal growth while the maternal environment predominantly alters the adiposity
      of the fetus.

PMID- 16085376
TI  - A comparison of the effects of equine luteinizing hormone (eLH), equine growth
      hormone (eGH) and human recombinant insulin-like growth factor (hrIGF-I) on
      steroid production in cultured equine Leydig cells during sexual maturation.
AB  - There are several hormones and local testicular factors involved in the
      initiation and control of steroidogenesis and spermatogenesis during puberty. GH
      and its mediator, IGF-I, increase substantially during puberty, and in addition
      to LH, these growth-promoting hormones can have direct effects upon testicular
      function. The objective of this work was to investigate the effects of eLH, eGH
      and hrIGF-I upon Leydig cells derived from testes of colts and stallions
      representing different stages of development. Testes were obtained from 48 light
      horse colts and stallions at the time of routine castration, horses were
      categorized according to age group (prepubertal, pubertal and postpubertal) and a
      Leydig cell enriched preparation was utilized for cell culture. Cells derived
      from all 48 horses were treated with doses of eLH, and a subset of 21 horses
      received doses of eGH and hrIGF-I. Cells were plated at a concentration of 1 x
      10(6) cells/ml and incubated for 24 h at 32 degrees C. Production of testosterone
      and estradiol was measured by validated RIA. Leydig cells from prepubertal colts
      secreted greater basal amounts of testosterone but lesser basal amounts of
      estradiol compared with the other age groups (p < 0.001). Pubertal stallions
      exhibited the greatest relative response to eLH (p < 0.05). Neither eGH nor hrIGF
      I elicited a steroidogenic response over baseline concentrations in any of the
      three age groups.

PMID- 16085377
TI  - Anti-ulcerogenic activity of some plants used in folk medicine of Pinarbasi
      (Kayseri, Turkey).
AB  - Several ethnomedicinal plant remedies used in Pinarbasi, Kayseri, in particular
      those which are used for the treatment of several peptic ulcer symptoms such as
      stomach ache, heartburn, etc. were selected for evaluation of their anti
      ulcerogenic potential. In order to confirm the claimed activities, decoctions
      were prepared from aerial parts of Malva neglecta Wallr. (Malvaceae), leaves of
      Potentilla reptans L. (Rosaceae), fruits of Rumex patientia L. (Polygonaceae),
      aerial parts of Sanguisorba minor Scop. ssp. muricata (Spach) Briq. (Rosaceae),
      aerial parts of Sideritis caesarea Duman, Aytac&Baser (Lamiaceae), and flowers of
      Verbascum cheiranthifolium Boiss var. cheiranthifolium (Scrophulariaceae)
      according to their described folkloric applications. Pharmacological experiments
      clearly demonstrated that the extracts of all plants given orally showed
      significant gastric protection against the ethanol-induced gastric ulcer model in
      rats. Furthermore, healing effects were also confirmed through histopathological
      examination.

PMID- 16085378
TI  - Hepatoprotective activity of Thunbergia laurifolia Linn extract in rats treated
      with ethanol: in vitro and in vivo studies.
AB  - Primary cultures of rat hepatocyte and rats were used as the in vitro and in vivo
      models to evaluate the hepatoprotective activity of aqueous extract from
      Thunbergia laurifolia (TLE). Ethanol was selected as hepatotoxin. Silymarin (SL)
      was the reference hepatoprotective agent. In the in vitro study, MTT reduction
      assay and release of transaminases (ALT and AST) were the criteria for cell
      viability. Primary cultures of rat hepatocyte (24 h culturing) were treated with
      ethanol (96 microl/ml) and various concentrations of TLE (2.5, 5.0, 7.5 and 10.0
      mg/ml) or SL (1, 2 and 3 mg/ml) for 2 h. Ethanol decreased MTT (%) nearly by
      half. Both TLE and SL increased MTT reduction and brought MTT (%) back to normal.
      Ethanol induced release of ALT and AST was also reduced by TLE (2.5 and 5.0
      mg/ml) and SL (1 mg/ml). In the in vivo study, serum transaminases, serum
      triglyceride (STg) together with hepatic triglyceride (HTg) and histopathological
      examination were the criteria for evidences of liver injury. Ethanol (4 g/(kg
      day), po for 14 days) caused the increase in ALT, AST, HTg and centrilobular
      hydropic degeneration of hepatocytes. TLE at 25 mg/(kg day), po, or SL at 5
      mg/(kg day), po, for 7 days after ethanol enhanced liver cell recovery by
      bringing HTg, ALT and/or AST back to normal. These results suggest that TLE and
      SL possess the hepatoprotective activity against ethanol induced liver injury in
      both primary cultures of rat hepatocyte and rats.

PMID- 16085379
TI  - Anthelmintic activity of Calotropis procera (Ait.) Ait. F. flowers in sheep.
AB  - The anthelmintic activity of Calotropis (C.) procera flowers in comparison with
      levamisole was evaluated through in vitro and in vivo studies. In vitro studies
      revealed anthelmintic effects (P<0.05) of crude aqueous (CAE) and crude
      methanolic extracts (CME) of Calotropis procera flowers on live Haemonchus (H.)
      contortus as evident from their mortality or temporary paralysis. For in vivo
      studies, Calotropis procera flowers were administered as crude powder (CP), CAE
      and CME to sheep naturally infected with mixed species of gastrointestinal
      nematodes. Egg count percent reduction (ECR) was recorded as 88.4 and 77.8% in
      sheep treated with CAE and CP at 3gkg(-1) body weight on day 7 and 10 post
      treatment (PT), respectively. CME was least effective resulting in 20.9%
      reduction in ECR on day 7 PT. It was found that Calotropis procera flowers
      possess good anthelmintic activity against nematodes, yet it was lower than that
      exhibited by levamisole (97.8-100%). It is suggested that further research on
      large scale be carried out involving a large number of animals, doses higher than
      those used in the current study, identification of active principles, and
      standardization of dose and toxicity studies for drug development.

PMID- 16085380
TI  - Lifelong heterogeneity in fecundity is insufficient to explain late-life
      fecundity plateaus in Drosophila melanogaster.
AB  - Previous studies have demonstrated that fecundity, like mortality, plateaus at
      late ages in cohorts of Drosophila melanogaster. Although evolutionary theory can
      explain the decline and plateau in cohort fecundity at late ages, it is
      conceivable that lifelong heterogeneity in individual female fecundity is
      producing these plateaus. For example, consistently more fecund females may die
      at earlier ages, leaving only females that always laid a low number of eggs
      preponderant at later ages. We simulated fecundity within a cohort, assuming the
      two phenotypes described above, and tested these predictions by measuring age of
      death and age-specific fecundity for individual females from three large cohorts.
      We statistically tested whether there was enough lifelong heterogeneity in
      fecundity to produce a late-life plateau by testing whether early female
      fecundity could predict whether that female would live to lay eggs after the
      onset of the population fecundity plateau. Our results indicate that
      heterogeneity in fecundity is not lifelong and thus not likely to cause late-life
      fecundity plateaus. Because lifelong heterogeneity models for fecundity are based
      on the same underlying assumptions as heterogeneity models for late-life
      mortality rates, our test of this hypothesis is also an experimental test of
      lifelong heterogeneity models of late life generally.

PMID- 16085381
TI  - MRI findings of Wernicke encephalopathy revisited due to hunger strike.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the
      characteristic magnetic resonance imaging (MRI) findings among a group of
      patients who presented with Wernicke encephalopathy (WE) due to the neurological
      complications of a long-term hunger strike (HS). METHODS: MRI studies also
      including the fluid-attenuated inversion recovery (FLAIR) sequence and diffusion
      weighted imaging (DWI) of six male patients with WE aged from 25 to 38 years
      (mean age 31 years) were evaluated. RESULTS: In all subjects, T2-weighted
      sequences, FLAIR and DWI revealed a signal hyperintensity within the
      posteromedial thalami and surrounding the third ventricle. In particular, on
      coronal images, the hyperintense areas around the third ventricle showed a
      suggestive "double wing" configuration. We observed an increased signal on proton
      density and T2-weighted images in the mamillary bodies of three patients. Four
      patients demonstrated additional hyperintensities within the periaqueductal
      region and/or the tectal plate. At least one lesion area in five of six patients
      demonstrated contrast enhancement. CONCLUSION: The consistent imaging findings of
      our study suggest that MRI is a reliable means of diagnosing WE. Acute WE is
      sometimes underdiagnosed, yet early diagnosis and treatment of WE is crucial in
      order to avoid persistent brain damage. MRI, including postcontrast T1-weighted
      imaging, DWI beneath standardized T2-weighted imaging, and FLAIR sequences may
      prove to be a valuable adjunct to clinical diagnosis and to provide additional
      information in acute and/or subacute WE.

PMID- 16085382
TI  - Polymorphisms associated with the DAZ genes on the human Y chromosome.
AB  - The human Y chromosome is unique in that it does not engage in pairing and
      crossing over during meiosis for most of its length. Y chromosome microdeletions,
      a frequent finding in infertile men, thus occur through intrachromosomal
      recombination, either within a single chromatid or between sister chromatids. A
      recently identified polymorphism associated with increased risk for spermatogenic
      failure, the gr/gr deletion, removes two of the four Deleted in Azoospermia (DAZ)
      genes in the AZFc region on the Y-chromosome long arm. We found the likely
      reciprocal duplication product of gr/gr deletion in 5 (6%) of 82 males using a
      novel DNA-blot hybridization strategy and confirmed the presence of six DAZ genes
      in three cases by FISH analysis. Additional polymorphisms identified within the
      DAZ repeat regions of the DAZ genes indicate that sister chromatid exchange plays
      a significant role in the genesis of deletions, duplications, and polymorphisms
      of the Y chromosome.

PMID- 16085383
TI  - Non-homogenous neural networks with chaotic recursive nodes: connectivity and
      multi-assemblies structures in recursive processing elements architectures.
AB  - This paper addresses recurrent neural architectures based on bifurcating nodes
      that exhibit chaotic dynamics, with local dynamics defined by first order
      parametric recursions. In the studied architectures, logistic recursive nodes
      interact through parametric coupling, they self organize, and the network evolves
      to global spatio-temporal period-2 attractors that encode stored patterns. The
      performance of associative memories arrangements is measured through the average
      error in pattern recovery, under several levels of prompting noise. The impact of
      the synaptic connections magnitude on architecture performance is analyzed in
      detail, through pattern recovery performance measures and basin of attraction
      characterization. The importance of a planned choice of the synaptic connections
      scale in RPEs architectures is shown. A strategy for minimizing pattern recovery
      degradation when the number of stored patterns increases is developed.
      Experimental results show the success of such strategy. Mechanisms for allowing
      the studied associative networks to deal with asynchronous changes in input
      patterns, and tools for the interconnection between different associative
      assemblies are developed. Finally, coupling in heterogeneous assemblies with
      diverse recursive maps is analyzed, and the associated synaptic connections are
      equated.

PMID- 16085384
TI  - Neural dynamics of psychotherapy: what modeling might tell us about us.
AB  - A neural network theory is proposed for some of the effects of verbal
      psychotherapy in individuals who are not seriously disturbed but seeking to
      function more effectively. The network theories are built on a combination of the
      supervised ARTMAP network and competitive attractor dynamics. The modeling
      exercise leads to some guidelines for psychotherapists that involve both
      cognitive and emotional reinforcement in a climate closer to skill learning than
      to medical treatment.

PMID- 16085385
TI  - Efficient streaming text clustering.
AB  - Clustering data streams has been a new research topic, recently emerged from many
      real data mining applications, and has attracted a lot of research attention.
      However, there is little work on clustering high-dimensional streaming text data.
      This paper combines an efficient online spherical k-means (OSKM) algorithm with
      an existing scalable clustering strategy to achieve fast and adaptive clustering
      of text streams. The OSKM algorithm modifies the spherical k-means (SPKM)
      algorithm, using online update (for cluster centroids) based on the well-known
      Winner-Take-All competitive learning. It has been shown to be as efficient as
      SPKM, but much superior in clustering quality. The scalable clustering strategy
      was previously developed to deal with very large databases that cannot fit into a
      limited memory and that are too expensive to read/scan multiple times. Using the
      strategy, one keeps only sufficient statistics for history data to retain (part
      of) the contribution of history data and to accommodate the limited memory. To
      make the proposed clustering algorithm adaptive to data streams, we introduce a
      forgetting factor that applies exponential decay to the importance of history
      data. The older a set of text documents, the less weight they carry. Our
      experimental results demonstrate the efficiency of the proposed algorithm and
      reveal an intuitive and an interesting fact for clustering text streams-one needs
      to forget to be adaptive.

PMID- 16085386
TI  - Dynamical systems and cognitive linguistics: toward an active morphodynamical
      semantics.
AB  - We propose a novel dynamical system approach to cognitive linguistics based on
      cellular automata and spiking neural networks. How can the same relationship 'in'
      apply to containers as different as 'box', 'tree' or 'bowl'? Our objective is to
      categorize the infinite diversity of schematic visual scenes into a small set of
      grammatical elements and elucidate the topology of language. Gestalt-inspired
      semantic studies have shown that spatial prepositions such as 'in' or 'above' are
      neutral toward the shape and size of objects. We suggest that this invariance can
      be explained by introducing morphodynamical transforms, which erase image details
      and create virtual structures or singularities (boundaries, skeleton), and call
      this paradigm 'active semantics'. Singularities arise from a large-scale lattice
      of coupled excitable units exhibiting spatiotemporal pattern formation, in
      particular traveling waves. This work addresses the crucial cognitive mechanisms
      of spatial schematization and categorization at the interface between vision and
      language and anchors them to expansion processes such as activity diffusion or
      wave propagation.

PMID- 16085387
TI  - Constructing Bayesian formulations of sparse kernel learning methods.
AB  - We present here a simple technique that simplifies the construction of Bayesian
      treatments of a variety of sparse kernel learning algorithms. An incomplete
      Cholesky factorisation is employed to modify the dual parameter space, such that
      the Gaussian prior over the dual model parameters is whitened. The regularisation
      term then corresponds to the usual weight-decay regulariser, allowing the
      Bayesian analysis to proceed via the evidence framework of MacKay. There is in
      addition a useful by-product associated with the incomplete Cholesky
      factorisation algorithm, it also identifies a subset of the training data forming
      an approximate basis for the entire dataset in the kernel-induced feature space,
      resulting in a sparse model. Bayesian treatments of the kernel ridge regression
      (KRR) algorithm, with both constant and heteroscedastic (input dependent)
      variance structures, and kernel logistic regression (KLR) are provided as
      illustrative examples of the proposed method, which we hope will be more widely
      applicable.

PMID- 16085388
TI  - Ovarian cancer diagnosis by hippocampus and neocortex-inspired learning memory
      structures.
AB  - Early detection and accurate staging of ovarian cancer are the keys to improving
      survival rate. However, at present there is no single diagnosis modality that is
      sufficiently sensitive. DNA microarray analysis is an emerging technique that has
      potential for ameliorating the hardship in early detection and staging of ovarian
      disease. However, microarray data is ultra-huge and difficult to analyze. Hence,
      computational intelligence methods are often utilized to assist in the diagnosis
      and analysis process. Fuzzy Neural Networks (FNN) are more suitable for this task
      as FNN provides not only the accuracy, but also the interpretability of its
      reasoning process. Hippocampus-inspired Complementary Learning FNN (CLFNN) is
      able to rapidly derive fuzzy sets and formulate fuzzy rules. CLFNN uses positive
      and negative learning, and hence it reduces the effect of the curse of
      dimensionality and is capable of modeling the dynamics of the problem space with
      relatively good classification performance. One of its successors, a hybrid of
      complementary hippocampal learning and associative neocortical learning called
      Pseudo Associative Complementary Learning (PACL), is a structure that seeks to
      functionally model the memory consolidation process. Both PACL and CLFNN have
      human-like reasoning that allows physicians to examine their computation using
      familiar terms. They can construct intuitive fuzzy rules autonomously to justify
      their reasoning, which is important to generate trust among the users. Hence,
      CLFNN and PACL are applied as a diagnostic decision support system in ovarian
      cancer diagnosis. The experimental results are encouraging.

PMID- 16085389
TI  - A comparative study of autoregressive neural network hybrids.
AB  - Many researchers have argued that combining many models for forecasting gives
      better estimates than single time series models. For example, a hybrid
      architecture comprising an autoregressive integrated moving average model (ARIMA)
      and a neural network is a well-known technique that has recently been shown to
      give better forecasts by taking advantage of each model's capabilities. However,
      this assumption carries the danger of underestimating the relationship between
      the model's linear and non-linear components, particularly by assuming that
      individual forecasting techniques are appropriate, say, for modeling the
      residuals. In this paper, we show that such combinations do not necessarily
      outperform individual forecasts. On the contrary, we show that the combined
      forecast can underperform significantly compared to its constituents'
      performances. We demonstrate this using nine data sets, autoregressive linear and
      time-delay neural network models.

PMID- 16085390
TI  - Worsening of psychotic symptoms in schizophrenia with addition of lamotrigine: a
      case report.

PMID- 16085392
TI  - Genomic instability in basal cell carcinomas.

PMID- 16085391
TI  - IFN-gamma regulates the expression of B7-H1 in dermal fibroblast cells.
AB  - BACKGROUND: Programmed cell death ligand 1 (B7-H1) was recently cloned in antigen
      presenting cells (APCs) and represents a third member of the B7 family. Thus, B7
      H1 may be a novel target for clinical intervention in human inflammatory disease.
      OBJECTIVE: The aim of this study is to investigate the signal transduction
      mechanism and transcriptional regulation of B7-H1 expression in human dermal
      fibroblasts. METHODS: We performed reverse transcription PCR (RT-PCR) for the
      detection of mRNA expression, luciferase reporter assays with B7-H1 promoter
      constructs, and Western blot analysis. RESULTS: From RT-PCR analysis, IFN-gamma
      can induce the expression of B7-H1 mRNA in dermal fibroblast. This expression is
      similar to the results of luciferase reporter assay with B7-H1 promoter. Western
      blot analysis and EMSA revealed that NF-kappaB transcription factors mediate the
      induction of B7-H1 expression via the transient phosphorylation of ERK1/2 and
      PI3K when cells are stimulated by IFN-gamma. Also, Specific destruction of the NF
      kappaB binding site abolished the induction of the promoter activity by IFN
      gamma. CONCLUSION: Our data not only provides the first evidence to demonstrate
      that dermal fibroblast express the B7-H1 mRNA in the process of skin
      inflammation, but also suggests the involvement of NF-kappaB and MAPK and PI3K,
      that may play some important roles in inflammation process in human skin
      diseases.

PMID- 16085393
TI  - rdlA, a new gene encoding a rhodanese-like protein in Halanaerobium congolense
      and other thiosulfate-reducing anaerobes.
AB  - The recently described anaerobic moderately halophilic bacterium Halanaerobium
      congolense has been shown to reduce thiosulfate and sulfur-but not sulfate-into
      sulfide. When cultivated in the presence of thiosulfate as terminal electron
      acceptor, H. congolense possesses a highly active thiosulfate:cyanide sulfur
      transferase activity (rhodanese-like enzyme). A gene library of H. congolense
      (DSM 11287T) was constructed, and a 3.1-kb Sau3A DNA that encompassed a
      thiosulfate:cyanide sulfur-transferase-encoding gene was isolated in Escherichia
      coli. This fragment contains 2 orfs, which were separately subcloned in E. coli.
      The 900-bp gene encoding the rhodanese-like protein was named rdlA. RdlA differs
      from other known rhodanese-like proteins by having two potential catalytic sites,
      one N-terminal and one C-terminal, both harboring a cysteine. The two putative
      active sites are preceded by a highly-conserved region of unknown function.
      Closely related genes were also characterized in other thiosulfate-reducing non
      sulfate-reducing anaerobes belonging to phylogenetically distant microorganisms,
      thus suggesting that RdlA is of importance in the mechanism of thiosulfate
      reduction by numerous members of the domain Bacteria.

PMID- 16085394
TI  - Prevotella massiliensis sp. nov. isolated from human blood.
AB  - We report a bacterial isolate (Marseille isolate) recovered from the blood of a
      patient hospitalized in an intensive care unit, presenting with severe trauma,
      fever and mechanical ventilation. Colonies appeared at 37 degrees C on blood agar
      after 72 h incubation. This isolate was a strictly anaerobic, Gram-negative rod
      phenotypically related to other Prevotella species described to date: non-motile,
      catalase-negative, oxidase-positive, non-glucose fermenting, resistant to
      vancomycin and susceptible to kanamycin. Cells exhibited a trilamellar membrane
      under electron microscopy. The fatty acid methyl ester profile was marginally
      related to that of Clostridium botulinum group A (distance: 26.27%) and
      Bifidobacterium bifidum GC subgroup B (distance: 26.38%). 16S rRNA gene sequence
      similarity was 90.0% with that of Prevotella oris and 89.1% with that of
      Prevotella melaninogenica. Partial rpoB gene sequence similarity was 84.5 and
      86.4% with P. oris and P. melaninogenica, respectively. According to current
      standards, phenotypic traits, 16S rRNA and rpoB gene sequence analyses indicated
      that the Marseille isolate belonged to a previously unrecognized species of the
      genus Prevotella, and we propose classifying it in the new taxon "Prevotella
      massiliensis" sp. nov.

PMID- 16085395
TI  - Sakacin P non-producing Lactobacillus sakei strains contain homologues of the
      sakacin P gene cluster.
AB  - Some strains of Lactobacillus sakei are known to produce the bacteriocin sakacin
      P, encoded by the spp gene cluster. In strains unable to produce sakacin P, spp
      homologues were observed. The analysis of 15 strains not producing sakacin P
      revealed that all contained a region corresponding to a part of sppKR encoding
      the regulatory elements for sakacin P production. In some strains homologues of
      sppE and sppT, responsible for sakacin P transport, and the sakacin P structural
      gene sppA and its immunity gene spiA, were also present. The sequence of the
      chromosomal spp-related gene cluster was determined in two non-producing strains:
      L. sakei Lb790 and L. sakei 23K. The L. sakei Lb790 spp gene cluster encompasses
      genes homologous to sppK, sppR, sppT and sppE. In L. sakei 23K, only sppK and
      sppR homologues were present. The sppK homologues appeared non-functional as they
      contained mutations and/or an insertion element. In addition to the spp
      homologues, several small putative genes were found in the gene clusters of the
      two strains. Some were similar in both strains, and their organization suggests a
      mosaic structure resulting from successive rearrangements. Transcriptional
      analysis showed that the genes of the L. sakei Lb790 spp cluster were expressed
      when genes encoding an operative sakacin P regulatory system were introduced in
      this strain, thus complementing the inactive sppK gene. Expression experiments
      also suggested that some of the spp homologues maintained their function in non
      producing strains.

PMID- 16085396
TI  - Tyrosine phosphatase MptpA of Mycobacterium tuberculosis inhibits phagocytosis
      and increases actin polymerization in macrophages.
AB  - Protein tyrosine phosphatases from several microorganisms have been shown to play
      a role as virulence factors by modifying the phosphorylation/dephosphorylation
      equilibrium in cells of their host. Two tyrosine phosphatases, MptpA and MptpB,
      secreted by Mycobacterium tuberculosis, have been identified. Expression of MptpA
      is upregulated upon infection of monocytes, but its role in host cells has not
      been elucidated. A eukaryotic expression vector containing the mptpA cDNA has
      been transfected into macrophages. We report that MptpA reduced phagocytosis of
      mycobacteria, opsonized zymosan or zymosan, but had no effect on phagocytosis of
      IgG-coated particles. We also noted that the presence of F-actin at the surface
      of phagosomes containing opsonized zymosan was significantly increased in cells
      expressing MptpA. In the presence of recombinant MptpA, the process of actin
      polymerization at the surface of isolated phagosomes was increased; this was not
      the case in the presence of the phosphatase-dead mutant MptpA(C11S). MptpA had no
      effect when IgG-coated particles were present inside isolated phagosomes. These
      results indicate that, like other tyrosine phosphatases of pathogens, MptpA plays
      a role in phagocytosis and actin polymerization. However, MptpA had no effect on
      IgG particles, suggesting that its putative substrate(s) is not linked to the
      signaling pathways of Fcgamma receptors.

PMID- 16085397
TI  - Characterization of microorganisms isolated from lignite excavated from the
      Zahorie coal mine (southwestern Slovakia).
AB  - Microorganisms were isolated from lignite freshly excavated in the Zahorie coal
      mine (southwestern Slovakia) under conditions excluding contamination with either
      soil or air-borne microorganisms. The isolates represented both Prokarya and
      Eukarya (fungi). All were able to grow on standard media, although some
      microorganisms were unstable and became extinct during storage of coal samples.
      Bacteria belonged to the genera Bacillus, Staphylococcus, and Rhodococcus,
      according to both morphological criteria and ITS sequences. Several bacterial
      isolates were resistant to antibiotics. The presence of anaerobic bacteria was
      also documented, although they have not yet been identified. Fungal isolates were
      typified by using their ITS sequences. They belonged to the genera Trichoderma
      (Hypocrea), Penicillium, Epicoccum, Metarhizium (Cordyceps), and Cladosporium.
      Several fungi produced compounds with antibiotic action against standard
      bacterial strains. The evidence for the presence of microorganisms in native
      lignite was obtained by means of fluorescence microscopy, scanning electron
      microscopy, and electron microprobe analysis. Results demonstrated that
      microorganisms were able to survive in the low-rank coal over a long time period.

PMID- 16085398
TI  - Effect of Fusarium verticillioides on maize-root-associated Burkholderia
      cenocepacia populations.
AB  - Burkholderia cepacia complex (Bcc) bacteria are naturally present in the
      rhizosphere of several crop plants and have been found to antagonize a wide range
      of important plant pathogens. In this study, we evaluated the effect of the
      pathogenic fungus Fusarium verticillioides on Bcc populations recovered from the
      roots of Zea mays plants. Maize plants were cultivated under greenhouse
      conditions and bacterial colonies were randomly isolated from distinct root
      portions of Fusarium-treated and control plants. We obtained a total of 120 Bcc
      isolates which all belonged to the species Burkholderia cenocepacia, a species of
      the Bcc widely distributed in natural habitats such as the rhizosphere of several
      crop plants. Results obtained revealed that the presence of the plant pathogen F.
      verticillioides had an effect at the root colonization level of B. cenocepacia
      populations, since an increase in indigenous B. cenocepacia bacteria was found in
      the rhizospheres of maize plants grown in infested soil, compared to the
      rhizospheres of control plants. The analysis of diversity indices as well as the
      investigation of genetic polymorphism of B. cenocepacia strains, isolated from
      Fusarium-treated and control root portions, revealed greater genetic variability
      in the presence of F. verticillioides, especially in the terminal root system
      portion. Finally, all B. cenocepacia isolates were also tested for in vitro
      inhibition of F. verticillioides growth as a functional property. Our results
      revealed that all B. cenocepacia isolates were able to restrict in vitro fungal
      growth, suggesting that there was no relationship between genetic polymorphism
      and biocontrol traits.

PMID- 16085399
TI  - Adsorption of hydrophobin proteins at hydrophobic and hydrophilic interfaces.
AB  - The surface activity of two hydrophobin proteins, HFBII and SC3, at the solid
      liquid, liquid-liquid and liquid-vapor interface has been investigated.
      Hydrophobins are fungal proteins that are known to adsorb and affect the physico
      chemical properties of an interface. In this study, the surface activity was
      determined by measuring the interaction of hydrophobin molecules with various
      liquids, solid particles and films that are commonly used or produced in
      industrial processes. We found that a very low concentration of hydrophobin is
      required to facilitate the wet-in of hydrophobic solid particles, such as Teflon,
      into aqueous solutions. It is also capable of stabilizing aqueous dispersions of
      Kevlar nanopulp, reversing the wettability of hydrophobic films and stabilizing
      polyunsaturated fatty acid (PUFA) oil-in-water emulsions.

PMID- 16085400
TI  - Population pharmacokinetic modeling for enterohepatic recirculation in Rhesus
      monkey.
AB  - Enterohepatic recirculation (EHR) occurs via biliary excretion and intestinal
      reabsorption of a drug. Drug recycling through EHR can lead to a change in
      pharmacokinetic (PK) properties, such as reduced clearance (CL), extended half
      life (T(1/2)) and increased plasma exposure (AUC). As a result, EHR may prolong
      the pharmacological effect of drugs. In the present study, the compound (Cpd A)
      was found to exhibit EHR in Rhesus monkeys associated with a reduction in CL
      (from 3.8 to 0.33 Lh(-1), IV; from 2.3 to 0.4 Lh(-1), PO), and an increase in
      T(1/2) (from 0.9 to 18 h, IV) and in AUC (from 1.5 to 17.4 microg h/mL, IV; from
      2.8 to 16.3 microg h/mL, PO), by comparing the PK in the monkeys via the
      interruption of EHR (bile-duct cannulation) with that in the intact monkeys. A
      population four-compartment model was constructed based on recirculation loops
      incorporating all possible inputs (bile secretion, a lag-time model for gall
      bladder emptying, routes and amounts of a single dose administration) to fully
      evaluate the EHR of Cpd A. The plasma concentrations versus time profiles
      predicted from the model had a good fit to the values observed in the subjects
      and were further simulated with 90% confidence interval to demonstrate its
      utility. Thus, the model could be applied as a useful tool to evaluate the drugs
      or compounds that undergo EHR in different species.

PMID- 16085401
TI  - [Spontaneous pneumothorax and azygos lobe in a child].

PMID- 16085402
TI  - A landmark extraction method for protein 2DE gel images based on multi
      dimensional clustering.
AB  - OBJECTIVE: Two-dimensional electrophoresis (2DE) is a separation technique that
      can identify target proteins existing in a tissue. Its result is represented by a
      gel image that displays an individual protein in a tissue as a spot. However,
      because the technique suffers from low reproducibility, a user should manually
      annotate landmark spots on each gel image to analyze the spots of different
      images together. This operation is an error-prone and tedious job. For this
      reason, this paper proposes a method of extracting landmark spots automatically
      by using a data mining technique. METHOD AND MATERIAL: A landmark profile which
      summarizes the characteristics of landmark spots in a set of training gel images
      of the same tissue is generated by extracting the common properties of the
      landmark spots. On the basis of the landmark profile, candidate landmark spots in
      a new gel image of the same tissue are identified, and final landmark spots are
      determined by the well-known A* search algorithm. RESULT AND CONCLUSIONS: The
      performance of the proposed method is analyzed through a series of experiments in
      order to identify its various characteristics.

PMID- 16085403
TI  - Non-HLA immunogenetics in hematopoietic stem cell transplantation.
AB  - Hematopoietic stem cell transplantation (HSCT) provides a unique environment in
      which to evaluate the role of immunogenetics of both the donor and the recipient
      to success of the procedure. The central role of HLA matching in HSCT has been
      established; however, recipients of allogeneic HSCT incur the risk of graft
      versus host disease (GVHD) even when the donor is a sibling who shares the major
      histocompatibility genes. Therefore, the perfect HLA match does not represent the
      optimal genetic make up. Other genetic systems operate and affect the various
      outcomes of HSCT, including GVHD, infections, transplant-related mortality, and
      overall survival. Minor histocompatibility antigens contribute to the control of
      GVHD as well as graft versus leukaemia reactions. In addition, genes controlling
      inflammatory processes, including cytokines, chemokines and their receptors, can
      modulate GVHD, and genes from both arms of the immune response (innate and
      adaptive) are strong candidates for susceptibility factors to infections in
      allogenic transplantation.

PMID- 16085405
TI  - KIR matching in hematopoietic stem cell transplantation.
AB  - Although the key role of MHC-restricted T lymphocytes in hematopoietic stem cell
      transplantation (HSCT) has been known for a long time, recent data have focused
      on complementary or alternative effector cell populations, and in particular on
      NK cells. Spontaneously generated NK cell alloreactivity from stem cell grafts
      involves specific interactions between NK receptors, including killer
      immunoglobulin-like receptors (KIRs) and their MHC class I ligands. The combined
      effects of HLA and KIR polymorphic genes might explain discrepancies in the
      impact of donor-recipient matching observed in HSCT.

PMID- 16085406
TI  - Immunogenetics today: HLA, MHC and much more.

PMID- 16085407
TI  - HLA genomics in the third millennium.
AB  - The MHC region contains several unique characteristics that set it apart as the
      most important region in the vertebrate genome in relation to disease. Recent
      data fit with the long-held view that the polymorphism of this region is driven
      by resistance to infection, although this is not yet proven. Interestingly, the
      MHC gene complex is associated with most, if not all, of the common autoimmune
      conditions. It has been difficult to identify the precise MHC genes associated
      with infection and autoimmunity, mainly because of the strong linkage
      disequilibrium over the region. Over the past few years, tools have been
      developed in an attempt to overcome these problems, including multiple fully
      sequenced MHC haplotypes, which have led to high-density hapmaps. In conjunction
      with large well-documented patient/control groups and sophisticated statistical
      methods these advances are starting to provide a comprehensive view of the
      genetics of the HLA region and disease susceptibility.

PMID- 16085408
TI  - Affinity-selected filamentous bacteriophage as a probe for acoustic wave
      biodetectors of Salmonella typhimurium.
AB  - Proof-in-concept biosensors were prepared for the rapid detection of Salmonella
      typhimurium in solution, based on affinity-selected filamentous phage prepared as
      probes physically adsorbed to piezoelectric transducers. Quantitative deposition
      studies indicated that approximately 3 x 10(10)phage particles/cm(2) could be
      irreversibly adsorbed for 1 h at room temperature to prepare working biosensors.
      The quality of phage deposition was monitored by fluorescent microscopy. Specific
      bacterial binding resulted in resonance frequency changes of prepared sensors,
      which were evaluated using linear regression analysis. Sensors possessed a rapid
      response time of <180 s, had a low-detection limit of 10(2)cells/ml and were
      linear over a range of 10(1)-10(7)cells/ml with a sensitivity of 10.9 Hz per
      order of magnitude of S. typhimurium concentration. Viscosity effects due to
      increasing bacterial concentration and non-specific binding were not significant
      to the piezoelectric platform as confirmed by dose-response analysis. Phage
      bacterial binding was confirmed by fluorescence and scanning electron microscopy.
      Overall, phage may constitute effective bioreceptors for use with analytical
      platforms for detecting and monitoring bacterial agents, including use in food
      products and possibly biological warfare applications.

PMID- 16085409
TI  - Quartz crystal microbalance bioaffinity sensor for biotin based on mixed self
      assembled monolayers and metastable molecular complex receptor.
AB  - A quartz crystal microbalance (QCM) sensor was proposed for the detection of
      small molecule biotin based on the mixed self-assembled monolayer (SAM) of thiols
      on gold substrate and the bioaffinity difference between an analyte (biotin) and
      an analogue compound (HABA) in binding avidin. Avidin formed a metastable complex
      with 2-[(4-hydroxyphenyl)azo]benzoic acid (HABA) immobilized on the crystal
      surface. When the sensor contacts a sample solution containing biotin, the avidin
      was released from the sensor surface to form a more stable complex with biotin in
      solution. The frequency change recorded is proportional to the desorbed mass of
      avidin, and there is a clear mathematic relationship between the frequency change
      and the biotin concentration. The use of mixed SAMs allows the stable attachment
      of bioreceptor molecules on the QCM, and enhances the amount of the immobilized
      molecules on the QCM, as a longer "space arm" in the mixed SAMs makes this
      monolayer membrane more accessible to capture the immobilized molecules. The
      proposed bioaffinity sensor has nice response to biotin in the range of 0.017
      1.67 microg/mL. The sensor could be regenerated under very mild conditions simply
      by reimmersion of the sensor into a biotin solution to desorb the surplus avidin.

PMID- 16085410
TI  - Epigenetic inheritance in Arabidopsis: selective silence.
AB  - Eukaryotic organisms have the remarkable ability to inherit states of gene
      activity without altering the underlying DNA sequence. This epigenetic
      inheritance can persist over thousands of years, providing an alternative to
      genetic mutations as a substrate for natural selection. Epigenetic inheritance
      might be propagated by differences in DNA methylation, post-translational histone
      modifications, and deposition of histone variants. Mounting evidence also
      indicates that small interfering RNA (siRNA)-mediated mechanisms play central
      roles in setting up and maintaining states of gene activity. Much of the
      epigenetic machinery of many organisms, including Arabidopsis, appears to be
      directed at silencing viruses and transposable elements, with epigenetic
      regulation of endogenous genes being mostly derived from such processes.

PMID- 16085411
TI  - Vitamin D compounds in leukemia.
AB  - The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3
      [1,25(OH)(2)D3,] possess in vitro multiple anti-cancer activities including
      growth arrest, induction of apoptosis and differentiation of a variety of
      different types of malignant cells. However, its use as a therapeutic agent is
      hindered by its calcemic effects. Analogs of 1,25(OH)(2)D3 have enhanced anti
      tumor activity, with reduced calcemic effects. However, limited clinical studies
      using vitamin D compounds have not yet achieved major clinical success.
      Nevertheless, pre-clinical studies suggest that the combination of either
      1,25(OH)(2)D3 or its analogs with other agents can have additive or synergistic
      anti-cancer activities, suggesting future clinical studies.

PMID- 16085412
TI  - First QSAR report on FSH receptor antagonistic activity: quantitative
      investigations on physico-chemical and structural features among 6-amino-4
      phenyltetrahydroquinoline derivatives.
AB  - A quantitative attempt has been made to correlate the structure-activity
      relationship (SAR) among the recently reported 6-amino-4
      phenyltetrahydroquinoline derivatives as antagonists for the Gs-protein-coupled
      human follicle-stimulating hormone (FSH) receptor. The compounds used for the
      present study have been reported to show high antagonistic efficacy in vitro
      using a CHO-hFSHR(luc) assay. Our QSAR investigations revealed a hydrophobic type
      of interactions between these ligands and the FSH receptor, hence confirming the
      presence of a lipophilic pocket on the active site of the target structure. The
      positive coefficient of ClogP variable in our derived QSAR model suggests that
      more hydrophobic ligands are crucial for their FSH receptor antagonistic
      efficacy. In exploring the structural requirements among these congeners, we
      found an amide linkage as conducive to their FSH receptor antagonistic activity.
      Also, an unsubstituted 4-phenyl ring of the tetrahydroquinoline scaffold is
      favorable for their FSH receptor antagonistic activity. The results discussed
      herein could be useful in understanding the nature of interactions of these newly
      identified ligands as FSH receptor antagonists and in designing more potent
      ligands based on this novel 6-amino-4-phenyltetrahydroquinoline scaffold.

PMID- 16085413
TI  - Synthesis and cytotoxic activity of platinum complex immobilized by branched
      polyethylene glycol.
AB  - Two-arm branched mPEG (monomethoxy-polyethylene glycol) with different molecular
      weights (M(n)=4000, 6000, 9400) was synthesized and used as carrier for
      immobilization of cisplatin [cis-diammine(dichloro)platinum (II), CDDP]. As a
      contrast, CDDP modified with linear mPEGs was also synthesized. All these
      polymeric drugs modified with branched mPEG are water soluble and show higher
      cytotoxic activity against C6 human breast cancer cells than cisplatin modified
      with linear mPEG with the same molecular weight. All the polymeric CDDP showed a
      much lower toxicity than the CDDP.

PMID- 16085414
TI  - Identification of ortho-amino benzamides and nicotinamides as MCHr1 antagonists.
AB  - Several potent and efficacious MCHr1 antagonists containing an ortho-amino
      benzamide or nicotinamide chemotype have been identified, exemplified by 28 and
      50.

PMID- 16085415
TI  - Novel, selective indole-based ECE inhibitors: lead optimization via solid-phase
      and classical synthesis.
AB  - A novel class of indole-based endothelin-converting enzyme (ECE) inhibitors was
      identified by high throughput screening. We report systematic optimization of
      this compound class by means of classical and solid-phase chemistry. Optimized
      compounds with a bisarylamide side chain at the 2-position of the indole skeleton
      exhibit low-nanomolar activity on ECE.

PMID- 16085416
TI  - Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors
      of DPP4, FAP, and DPP7.
AB  - The structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives
      against three dipeptidyl peptidases (DPPs) was studied. In a series of N
      cycloalkyl analogs, DPP4 and fibroblast activation protein-alpha (FAP) optimally
      preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly
      alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro
      resulted in a significant decrease in potency against all the three DPPs.

PMID- 16085417
TI  - A short history of the World Muscle Society.

PMID- 16085418
TI  - The severity, outcome and challenges of breast cancer in Nigeria.
AB  - Breast cancer is a very common disease in Nigeria. It is often associated with a
      poor prognosis for a variety of reasons. This study was designed to investigate
      the challenges, severity, outcome and factors influencing the outcome of the
      management of breast cancer in a Nigerian Teaching Hospital with a view to
      finding ways to improve the current dismal outlook for patients with the disease.
      The clinical records of patients seen with breast cancer over an 8-year period
      (1996-2003) in the two units of the Teaching hospital were reviewed. The two
      units serve the urban, semi-urban and rural communities of some parts of
      southwestern Nigeria. Two hundred and twelve patients with breast cancer were
      seen over the 8-year period of the study. The mean age was 48 years (23-85
      years). There were 211 female and one male. One hundred and three patients
      (48.7%) had either postprimary or tertiary education. A proportion of 66.7% were
      premenopausal, 79.2% had pregnancy early in life and were multi-parous. These
      also gave a history of prolonged breast-feeding of their children. The tumour was
      self-detected in 195 (92%). The mean duration of symptoms was 11.2 months (9 days
      7 years). Pain in 100 patients (47%) was the most common symptom and the cancer
      was in the left breast in 113 (53.3%). Localized cancer was in the upper outer
      quadrant in 85 (40%), whereas the whole breast was involved in 55 patients (26%).
      Loco-regional features of advanced cancer were seen in 157 patients (74%). The
      tumour was fungating in 83 (39%) and there was clinical evidence of systemic
      metastasis in 28 patients (13%). One hundred and seventy-four (80.6%) patients
      had advanced disease (stages 3 and 4). Definitive surgery was possible in 185
      patients (87.3%), neoadjuvant chemotherapy was required in 65 (30.6%),
      postoperative adjuvant chemotherapy in 178 (84%; drug combinations were CMF
      cyclophosphamide, methotrexate, 5-fluorouracil, CMFP-CMF plus prednisone, and CAF
      cyclophosphamide, adriamycin, 5-fluorouracil), tamoxifen was administered in all
      the patients. Only 70 (33.2%) patients were known to have received radiotherapy
      among those referred to the Radiotherapy unit, with associated fair treatment
      compliance after surgery. Outpatient clinic attendance was also very poor, only
      27 (12.7%) were still being seen in the clinic, 83 patients (39%) were known to
      be dead and 102 patients were lost to follow-up. The mean follow-up period was
      8.4 months (1 week-6 years). In conclusion, breast cancer is very common in our
      area of practice in Nigeria; the majority of our patients were young and
      premenopausal women presenting in the advanced stages of cancer. Treatment
      compliance was very poor. The majority of the patients were dead or lost to
      follow-up within a year of diagnosis.

PMID- 16085419
TI  - Validation of a histamine H3 receptor model through structure-activity
      relationships for classical H3 antagonists.
AB  - Histamine H(3) receptor is a G protein-coupled receptor whose activation inhibits
      the synthesis and release of histamine and other neurotransmitters from nerve
      endings and is involved in the modulation of different central nervous system
      functions. H(3) antagonists have been proposed for their potential usefulness in
      diseases characterized by impaired neurotransmission and they have demonstrated
      beneficial effects on learning and food intake in animal models. In the present
      work, a 3D model of the rat histamine H(3) receptor, built by comparative
      modeling from the crystallographic coordinates of bovine rhodopsin, is presented
      with the discussion of its ability to predict the potency of known and new H(3)
      antagonists. A putative binding site for classical, imidazole-derived H(3)
      antagonists was identified by molecular docking. Comparison with a known
      pharmacophore model and the binding affinity of a new rigid H(3) antagonist
      (compound 1, pK(i)=8.02) allowed the characterization of a binding scheme which
      could also account for the different affinities observed in a recently reported
      series of potent H(3) antagonists, characterized by a 2-aminobenzimidazole
      moiety. Molecular dynamics simulations were employed to assess the stability and
      reliability of the proposed binding mode. Two new conformationally constrained
      benzimidazole derivatives were prepared and their binding affinity was tested on
      rat brain membranes; compound 9, designed to reproduce the conformation of a
      known potent H(3) antagonist, showed higher potency than compound 8, as expected
      from the binding scheme hypothesized.

PMID- 16085420
TI  - Polyelectrolytes as new matrices for secondary ion mass spectrometry.
AB  - Significant enhancements in ion yields in time-of-flight secondary ion mass
      spectrometry (TOF-SIMS) are observed when water-soluble analytes are mixed with a
      polyelectrolyte, e.g., poly(diallyldimethylammonium chloride) or poly(sodium 4
      styrenesulfonate), and then deposited in the layer-by-layer method on a surface.
      This previously unobserved effect is demonstrated for 5-chloro-8-methoxyquinoline
      appended diaza-18-crown-6, 5-(2-aminoethoxy)methyl-5-chloro-8-methoxyquinoline
      appended diaza-18-crown-6, acridine, 9-anthracenecarboxylic acid, and
      ferrocenecarboxylic acid. By optical ellipsometry film thicknesses range from ca.
      5-20 angstroms. X-ray photoelectron spectroscopy shows significantly less analyte
      in the polyelectrolyte-analyte films than in the neat analytes. However, TOF-SIMS
      generally shows significant enhancements in ion yields from the polyelectrolyte
      films compared with either the neat compounds or the compounds solubilized with
      acid or base and then dried on a surface. These significant enhancements in ion
      yields also appear to extend to analyte fragments and cationized molecular
      species. Some enhancement is also observed for dried droplets of analytes mixed
      with a polyelectrolyte on surfaces.

PMID- 16085421
TI  - Electrospray mass spectrometry for the direct accurate mass measurement of
      ligands in complex with the retinoid X receptor alpha ligand binding domain.
AB  - Accurate mass measurements are often used in the structural determination of
      unknown compounds of low molecular mass (i.e., below approximately 500 Da).
      Recently, it has been shown that accurate mass measurements also can be made on
      small denatured proteins (i.e., M(r), approximately 17,000) to confirm their
      amino acid composition and identify the presence of isoforms. In the current
      report, we present nondenaturing electrospray (ES) mass spectrometry data on the
      direct accurate mass measurement of ligands in complex with the retinoid X
      receptor ligand binding domain (RXR LBD; M(r) 31,370.92). Average mass errors
      were below 0.198 Da, 6.3 ppm (standard deviation [SD], 0.146; n = 10) for low
      affinity fatty acid agonists analyzed in complex with the RXR LBD. Protein
      consumption was less than 15 pmol, with fatty acid ligands present at
      concentrations corresponding to their median effective concentration value (low
      micromolar, determined in transfection assays). Although determination of fatty
      acid mass was only sufficiently accurate to give nominal mass values,
      measurements were of sufficient accuracy to assign fatty acid chain length,
      degree of unsaturation, or cyclization. Using 17beta-estradiol as a control, the
      ability to observe specific ligand binding is shown for both high- and low
      affinity RXRalpha agonists. In addition, binding of a novel synthetic receptor
      agonist XCT0315908 to the RXRalpha LBD is reported. This compound showed a high
      degree of complex formation, and the receptor-ligand complex could be mass
      measured with an average mass error of -0.024 Da, 0.8 ppm (SD, 0.092; n = 9).
      Thus, specific binding of both nanomolar and micromolar affinity ligands to a
      nuclear receptor LBD can be directly observed using nondenaturing ES mass
      spectrometry and accurate mass measurements additionally can be made on intact
      complexes in the same experiment. This methodology also is applicable when
      ligands are present as components of mixtures.

PMID- 16085422
TI  - Analysis of p300 acetyltransferase substrate specificity by MALDI TOF mass
      spectrometry.
AB  - Acetyltransferase enzymes target specific lysine residues in substrate proteins.
      While the list of histone and nonhistone substrates is growing, the mechanisms of
      substrate selection remain unclear. Here, we describe a mass spectrometric
      approach to examine the site selection of the acetyltransferase p300 in the HIV-1
      protein Tat. Tat is acetylated by p300 at a single lysine (K50) within its basic
      RNA-binding domain. To determine the sequence requirements for K50 recognition
      within this domain, we synthesized mixtures of "degenerated" Tat peptides, in
      which one of the surrounding residues was substituted by all proteinogenic amino
      acids. Peptide mixtures were assembled based on nonoverlapping peptide masses and
      acetylated by p300 in a standard in vitro acetylation reaction. Analysis by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      identified amino acid substitutions that prevented acetylation by p300. This
      approach represents a fast and comprehensive screening method that was applied to
      the six surrounding residues of K50 in Tat. It can be applied to any known
      acetyltransferase substrate and might help to define consensus recognition
      sequences for individual acetyltransferase enzymes.

PMID- 16085423
TI  - Microplate filtration assay for nicotinamide release from NAD using a boronic
      acid resin.
AB  - We describe a microplate-based assay for NAD-dependent Class III histone
      deacetylases (also known as SIRTs) that measures the enzyme-catalyzed release of
      nicotinamide from radiolabeled NAD, using a boronic acid resin to selectively
      capture the NAD. This method avoids the need for fluorogenic or radiolabeled
      peptides or separation of the reaction products using solvent extraction. The
      protocol reported here is rapid and uses commercially available materials. The
      use of a simple microplate filtration device allows for the simultaneous
      processing of 96 samples, facilitating enzyme kinetic analyses and inhibition
      studies. Furthermore, monitoring nicotinamide release rather than peptide
      deacetylation obviates the need for chemical modification of protein and peptide
      substrates. This assay is applicable to SIRTs and other enzymes that cleave
      nicotinamide from NAD.

PMID- 16085424
TI  - Assays for mechanistic investigations of protein/histone acetyltransferases.
AB  - Protein/histone acetyltransferases (PATs/HATs) have been implicated in a number
      of cellular functions including gene regulation, DNA synthesis, and repair. This
      paper reviews methods that can be used to quantitatively determine the activity
      and ultimately the catalytic/kinetic mechanism of PAT/HATs in vitro. Two methods
      will be described in detail. The first method is a filter-binding assay that
      measures the transfer of radiolabeled acetate from acetyl-CoA to protein. The
      second method is a continuous, spectroscopic, enzyme-coupled assay that links the
      PAT/HAT reaction to the reduction of NAD+ by pyruvate or alpha-ketoglutarate
      dehydrogenase. Both methods are highly applicable in determining steady-state
      reaction rates, and obtaining the kinetic constants Vmax, Km, and V/K from
      substrate saturation curves. We describe a new application of the filter-binding
      assay to determine the kinetic parameters for HATs using low concentrations of
      nucleosomal substrates.

PMID- 16085425
TI  - In nucleo enzymatic assays for the identification and characterization of histone
      modifying activities.
AB  - The impact of histone phosphorylation, acetylation, and methylation onto
      transcription and various other cellular DNA-mediated processes is now well
      established. Numerous histone modification marks, specific sites carrying
      particular post-translational modifications, have been described and analyzed in
      detail. Whereas, many methods for the study of histone post-translational
      modifications involve sophisticated equipment and techniques, we describe the
      revival of a very simple procedure for the analysis of histone modifications and
      histone modifying enzymes, which is derived from experiments first carried out
      several decades ago. This method is based on the isolation of cell nuclei
      containing intact chromatin structures that are then incubated with defined
      enzymatic substrates of histone modifying enzymes. We provide quick protocols for
      the isolation of nuclei from yeast and mammalian cells and give basic procedures
      for the phosphorylation, acetylation, and methylation of histones (and other
      proteins) using these subcellular sources that can be carried out in any
      laboratory. Simple methods for the analysis of histone modifications using these
      assays are discussed.

PMID- 16085426
TI  - Low doses of alcohol substantially decrease glucose metabolism in the human
      brain.
AB  - Moderate doses of alcohol decrease glucose metabolism in the human brain, which
      has been interpreted to reflect alcohol-induced decreases in brain activity.
      Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg
      and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the human
      brain. Twenty healthy control subjects were tested using positron emission
      tomography (PET) and FDG after placebo and after acute oral administration of
      either 0.25 g/kg, or 0.5 g/kg of alcohol, administered over 40 min. Both doses of
      alcohol significantly decreased whole-brain glucose metabolism (10% and 23%
      respectively). The responses differed between doses; whereas the 0.25 g/kg dose
      predominantly reduced metabolism in cortical regions, the 0.5 g/kg dose reduced
      metabolism in cortical as well as subcortical regions (i.e. cerebellum,
      mesencephalon, basal ganglia and thalamus). These doses of alcohol did not
      significantly change the scores in cognitive performance, which contrasts with
      our previous results showing that a 13% reduction in brain metabolism by
      lorazepam was associated with significant impairment in performance on the same
      battery of cognitive tests. This seemingly paradoxical finding raises the
      possibility that the large brain metabolic decrements during alcohol intoxication
      could reflect a shift in the substrate for energy utilization, particularly in
      light of new evidence that blood-borne acetate, which is markedly increased
      during intoxication, is a substrate for energy production by the brain.

PMID- 16085427
TI  - Empirical comparison of maximal voxel and non-isotropic adjusted cluster extent
      results in a voxel-based morphometry study of comorbid learning disability with
      schizophrenia.
AB  - We present an empirical comparison of cluster extent and maximal voxel results in
      a voxel-based morphometry (VBM) study of brain structure. The cluster extents are
      adjusted for underlying deviation from uniform smoothness. We implement this
      comparison on a four-group cohort that has previously shown evidence of a neuro
      developmental component in schizophrenia (Moorhead, T.W.J., Job, D.E., Whalley,
      H.C., Sanderson, T.L., Johnstone, E.C. and Lawrie, S.M. 2004. Voxel-based
      morphometry of comorbid schizophrenia and learning disability: analyses in
      normalized and native spaces using parametric and nonparametric statistical
      methods. NeuroImage 22: 188-202.). We find that adjusted cluster extent results
      provide information on the nature of deficits that occur in the schizophrenia
      affected groups, and these important structural differences are not all shown in
      maximal voxel results. The maximal voxel and cluster extent results are corrected
      for multiple comparisons using Random Fields (RF) methods. In order to apply the
      cluster extent measures, we propose a post-hoc method for determining the primary
      threshold in the analysis. Unadjusted cluster extent results are reported, for
      these, no allowance is made for non-isotropic smoothness, and comparison with the
      adjusted extent results shows that the unadjusted results can be either
      conservative or anti-conservative depending upon the underlying tissue
      distributions.

PMID- 16085428
TI  - The cerebral control of speech tempo: opposite relationship between speaking rate
      and BOLD signal changes at striatal and cerebellar structures.
AB  - So far, only sparse data on the cerebral organization of speech motor control are
      available. In order to further delineate the neural basis of articulatory
      functions, fMRI measurements were performed during self-paced syllable
      repetitions at six different frequencies (2-6 Hz). Bilateral hemodynamic main
      effects, calculated across all syllable rates considered, emerged within
      sensorimotor cortex, putamen, thalamus and cerebellum. At the level of the
      caudatum and the anterior insula, activation was found restricted to the left
      side. The computation of rate-to-response functions of the BOLD signal revealed a
      negative linear relationship between syllable frequency and response magnitude
      within the striatum whereas cortical areas and cerebellar hemispheres exhibited
      an opposite activation pattern. Dysarthric patients with basal ganglia disorders
      show unimpaired or even accelerated speaking rate whereas, in contrast,
      cerebellar dysfunctions give rise to slowed speech tempo which does not fall
      below a rate of about 3 Hz. The observed rate-to-response profiles of the BOLD
      signal thus might help to elucidate the pathophysiological mechanisms of
      dysarthric deficits in central motor disorders.

PMID- 16085429
TI  - A molecular timescale for caviomorph rodents (Mammalia, Hystricognathi).

PMID- 16085430
TI  - Phylogeography of Mabuya maculilabris (Reptilia) from Sao Tome Island (Gulf of
      Guinea) inferred from mtDNA sequences.
AB  - The pattern of genetic variation of the lizard Mabuya maculilabris from Sao Tome
      Island (Gulf of Guinea) was investigated using a combination of three
      mitochondrial DNA gene fragments. Forty-eight haplotypes were recovered among 66
      individuals covering the whole island. The genealogy inferred from the most
      parsimonious network of haplotypes allows us to detect two main and long branches
      departing from the putative group of oldest haplotypes. The tips of these
      branches exhibit star-like phylogenies, which may indicate of recently expanded
      populations, most probably from a small number of founders. A nested clade
      analysis suggests a complex pattern of past events that gave rise to the extant
      geographical pattern found in the haplotype distribution: past and allopatric
      fragmentation, range expansion, restricted gene flow and long-distance dispersal.
      These results are consistent with the complex geological history of the island
      where important volcanic activity with extensive lava flows has occurred during
      several periods. Mismatch-distribution analysis and AMOVA also support these
      conclusions. Substantial genetic structuring among these lizards was detected as
      well as high levels of differentiation between the southern edge populations
      (particularly those from the Rolas Islet) and the remaining ones. However,
      variation is low relative to the geological age of the island. Our results
      indicate that patterns of variation observed in reptiles in other oceanic islands
      are not indicative of those observed in the islands of the Gulf of Guinea.

PMID- 16085431
TI  - Lower level relationships in the mushroom genus Cortinarius (Basidiomycota,
      Agaricales): a comparison of RPB1, RPB2, and ITS phylogenies.
AB  - We sampled and analyzed approximately 2900bp across the three loci from 54 taxa
      belonging to a taxonomically difficult group of Cortinarius subgenus Phlegmacium.
      The combined analyses of ITS and variable regions of RPB1 and RPB2 greatly
      increase the resolution and nodal support for phylogenies of these closely
      related species belonging to clades that until now have proven very difficult to
      resolve with the ribosomal markers, nLSU and ITS. We present the first study of
      the utility of variable regions of the genes encoding the two largest subunits of
      RNA polymerase II (RPB1 and RPB2) for inferring the phylogeny of mushroom-forming
      fungi in combination with and compared to the widely used ribosomal marker ITS.
      The studied region of RPB1 contains an intron of the size and variability of ITS
      along with many variable positions in coding regions. Though almost entirely
      coding, the studied region of RPB2 is more variable than ITS. Both RNA polymerase
      II genes were alignable across all taxa. Our results indicate that several
      sections of Cortinarius need redefinition, and that several taxa treated at
      subspecific and varietal level should be treated at specific level. We suggest a
      new section for the two species, C. caesiocortinatus and C. prasinocyaneus, which
      constitute a well-supported separate lineage. We speculate that sequence
      information from RNA polymerase II genes have the potential for resolving
      phylogenetic problems at several levels of the diverse and taxonomically very
      challenging genus Cortinarius.

PMID- 16085432
TI  - Molecular systematics of the endemic Leptaxini (Gastropoda: Pulmonata) on the
      Azores islands.
AB  - The Azorean representatives of the Leptaxini (Pulmonata) are single island
      endemics, where a high-spired shell distinguishes the monotypic genus Helixena
      from two slightly different low-spired forms within Leptaxis (azorica and
      caldeirarum type). We studied the evolutionary history of putative taxa and the
      three shell-types using 12 allozyme loci and sequences of nuclear (ITS-1 and ITS
      2) and mitochondrial DNA (COI and 16S rRNA). While little variation was found in
      both ITS genes, allozyme and mtDNA divergence was among the highest reported for
      pulmonate land snails. Generally, phylogeographic patterns are indicative of
      allopatric differentiation via the successive colonization of (younger) islands,
      while a major role for adaptive evolution is not supported. The azorica shell
      type is monophyletic and has no common history with other sympatric shell-types
      on the same islands. The (ambiguous) position of Helixena sanctaemariae makes
      Leptaxis paraphyletic on the Azores and possibly also the caldeirarum shell-type.
      Helixena can therefore not be distinguished as a separate genus on the Azores.
      Following a lineage-based concept, representatives on all (ancient) islands
      should be considered distinct species.

PMID- 16085433
TI  - Generation of embryoid bodies from mouse embryonic stem cells cultured on STO
      feeder cells.
AB  - Embryoid bodies, which are similar to post-implantation egg-cylinder stage
      embryos, provide a model for the study of embryo development and stem cell
      differentiation. We describe here a novel method for generating embryoid bodies
      from murine embryonic stem (ES) cells cultured on the STO feeder layer. The ES
      cells grew into compact aggregates in the first 3 days of coculture, then became
      simple embryoid bodies (EBs) possessing primitive endoderm on the outer layer.
      They finally turned into cystic embryoid bodies after being transferred to Petri
      dishes for 1-3 days. Evaluation of the EBs in terms of morphology and
      differentiating potential indicates that they were typical in structure and could
      generate cells derived from the three germ layers. The results show that embryoid
      bodies can form not only in suspension culture but also directly from ES cells
      cultured on the STO feeder layer.

PMID- 16085434
TI  - Cellular organisation and differentiation of organelles in pre-meiotic rice
      anthers.
AB  - Pre-meiotic cellular organisation of rice anthers has a great significance in
      pollen formation. We have used a combination of confocal laser and transmission
      electron microscopy (TEM) to characterise and differentiate organelles in pre
      meiotic rice anthers. Along with the characteristic organelles in the cytoplasm
      the epidermal cells of the pre-meiotic rice anther are coated on their outer
      surface by a conspicuous bi-lamellate cuticle. Chloroplasts of the endothecium
      contain immature grana, thylakoids and also starch granules. These plastids
      clearly contain photosynthetic pigments as shown by autofluorescence in confocal
      microscope studies. Both confocal and TEM studies reveal clusters of mitochondria
      in the middle layer. The tapetum contains electron opaque ribosomes, bundles of
      mitochondria and plastids. The nuclei of the tapetum occupy a large volume of the
      cytoplasm indicating the onset of mitotic prophase. Intense Rhodamine 123
      staining reveals that a major portion of the structurally indistinguishable
      organelles that were seen throughout the densely ribosomic cytoplasm of
      sporogenous cells are mitochondria.

PMID- 16085435
TI  - Modulation of smooth muscle cell function: morphological evidence for a
      contractile to synthetic transition in the rat ventral prostate after castration.
AB  - In this study, we evaluated the involvement of rat ventral prostate smooth muscle
      cells (SMC) in secretory activity and whether this function is modulated after
      castration. Cell morphology was examined at both light and electron microscopy
      levels and the organelles involved in secretory function were labeled by the zinc
      iodide-osmium (ZIO) method at the ultrastructural level and their volume density
      was determined by stereology. Castration resulted in marked changes of the SMC,
      which adopted a spinous aspect and abandoned the layered arrangement observed in
      the prostates of non-castrated rats. The volume density of ZIO reactive
      organelles increased progressively after castration, reaching significantly
      higher levels 21 days after castration. Since previous studies have demonstrated
      that SMC express SMC markers (even 21 days after castration) and are able to
      respond to adrenergic stimulation, we concluded that differentiated SMC are able
      to shift from a predominantly contractile to a more synthetic phenotype without
      changing their differentiation status.

PMID- 16085436
TI  - A prospective study of cutaneous nerve injury following long saphenous vein
      surgery.
AB  - OBJECTIVES: The aim of this study was to identify the incidence and distribution
      of nerve damage in patients undergoing primary venous surgery. METHODS: Patients
      undergoing primary great saphenous vein surgery between February and November
      2003 were enrolled. In all cases the great saphenous vein was 'flush' ligated at
      the sapheno-femoral junction and stripped to the knee by inversion without using
      a stripper head; multiple phlebectomies were performed using an Oesch hook. A
      vascular nurse followed up patients 6 weeks post-operatively. Those reporting
      altered sensation and/or pain were examined by a doctor to provide an objective
      assessment of any neurological damage. These patients were again followed up by
      telephone at 6 and 12 months. RESULTS: Sixty-three limbs from 54 patients were
      enrolled. Numbness or paraesthesia was identified in 17 (27%) limbs at 6 week
      follow-up. 11 (17%) limbs were affected below the knee and 7 (11%) limbs were
      affected at the thigh or groin. One of the limbs was affected above and below the
      knee. Of these 17 limbs there was resolution in six limbs at 6 months and nine
      limbs at 12 months. Two patients with persistent nerve lesions regretted
      undergoing surgery. Patients undergoing bilateral surgery were more likely to
      report abnormal sensation (chi(2) test, p=0.006). There was no significant
      difference between the incidence of nerve injury for consultant, SpR or SHO as
      first operator (chi(2) test, p=0.9). CONCLUSION: This study demonstrates the
      frequency of nerve injury during primary great saphenous vein surgery. It will be
      useful for clinicians providing informed consent and may provide a benchmark for
      comparison with newer techniques.

PMID- 16085437
TI  - Analgesic efficacy and safety of intravenous paracetamol (acetaminophen)
      administered as a 2 g starting dose following third molar surgery.
AB  - BACKGROUND: The recommended dose for intravenous (IV) paracetamol injection in
      adults is 1g, however pharmacokinetic and pharmacodynamic findings suggest that a
      better analgesia could be obtained with a 2 g starting dose. METHODS: A single
      centre, randomised, double-blind, placebo-controlled, 3-parallel group study was
      performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2 g.
      Following third molar surgery, patients reporting moderate to severe pain
      received a single 15-min infusion of either IV paracetamol 2 g, IV paracetamol 1g
      or placebo. Efficacy and safety were evaluated over 8 h. Laboratory tests were
      performed before and 48 h after drug administration. RESULTS: Two hundred and
      ninety seven patients (132 = IV paracetamol 2g; 132 = IV paracetamol 1g; 33 =
      placebo) were randomised and completed the study. The summed pain relief over 6h
      (TOTPAR6) was significantly superior with IV paracetamol 2 g as compared to IV
      paracetamol 1g and placebo (p < 0.0001). Pain relief scores of IV paracetamol 2g
      were significantly superior to IV paracetamol 1g and to placebo from T30' to T8h
      (p < 0.0001). Median duration of analgesia was significantly longer following IV
      paracetamol 2 g compared to IV paracetamol 1g and placebo (p < 0.0001). Adverse
      events occurred with the same frequency in the 3 treatment groups. No clinically
      significant changes from baseline were observed for vital signs or laboratory
      tests. CONCLUSION: The analgesic efficacy of a 2 g starting dose of IV
      paracetamol was superior over the recommended dose of 1g in terms of magnitude
      and duration of analgesic effect for postoperative pain following third molar
      surgery, with no significant difference between groups regarding safety.

PMID- 16085438
TI  - Bayesian estimation of Karplus parameters and torsion angles from three-bond
      scalar couplings constants.
AB  - We apply Bayesian inference to analyze three-bond scalar coupling constants in an
      objective and consistent way. The Karplus curve and a Gaussian error law are used
      to model scalar coupling measurements. By applying Bayes' theorem, we obtain a
      probability distribution for all unknowns, i.e., the torsion angles, the Karplus
      parameters, and the standard deviation of the Gaussian. We infer all these
      unknowns from scalar coupling data using Markov chain Monte Carlo sampling and
      analytically derive a probability distribution that only involves the torsion
      angles.

PMID- 16085439
TI  - Ontogeny of cardiovascular control in zebrafish (Danio rerio): effects of
      developmental environment.
AB  - The goal of this symposium paper was to identify and quantify developmental
      plasticity in the onset of cardiovascular responses in the zebrafish.
      Developmental plasticity was induced by altering the developmental environment in
      one of three ways: (1) by developing zebrafish in a constant current of 5 body
      lengths per second, (2) by developing zebrafish at a colder temperature (20
      degrees C), and (3) by developing zebrafish in severe hypoxia (DO=0.8 mg/L).
      Early morphological development was significantly affected by each of the
      treatment environments with hypoxia slowing development the most and producing
      the highest variation in measurements. Development in constant water current did
      not significantly affect the timing onset of cardiovascular responses to the
      pharmacological agents applied. Development at 20 degrees C significantly delayed
      the onset of all cardiovascular responses measured by 2-3 days. Development in
      hypoxia, however, not only delayed onset of all cardiovascular responses, but
      also shifted the onset relative to the developmental program. Hypoxia clearly has
      a profound affect on the onset of cardiovascular regulation and it will take many
      more studies to elucidate the mechanisms by which hypoxia is having its effect.
      Furthermore, long term studies are also needed to assess whether the plasticity
      measured in this study is adaptive in the evolutionary sense.

PMID- 16085440
TI  - Why are some mitochondria more powerful than others: insights from comparisons of
      muscle mitochondria from three terrestrial vertebrates.
AB  - We studied the molecular composition of muscle mitochondria to evaluate whether
      the contents of cytochromes or adenine nucleotide translocase (ANT) or
      phospholipid acyl compositions reflect differences in mitochondrial oxidative
      capacities. We isolated mitochondria from three vertebrates of similar size and
      preferred temperature, the rat (Rattus norvegicus), the cane toad (Bufo marinus)
      and the bearded dragon lizard (Pogona vitticeps). Mitochondrial oxidative
      capacities were higher in rats and cane toads than in bearded dragon, whether
      rates were expressed relative to protein, cytochromes or ANT. Inter-specific
      differences were least pronounced when rates were expressed relative to
      cytochrome A, a component of cytochrome C oxidase (CCO), or ANT. In mitochondria
      from rat and cane toad, cytochrome A was more abundant than C followed by B and
      then C(1), while in bearded dragon mitochondria, the cytochromes were present in
      roughly equal levels. Analysis of correlations between mitochondrial oxidative
      capacities and macromolecular components revealed that cytochrome A explained at
      least half of the intra- and inter-specific variability in substrate oxidation
      rates. ANT levels were an excellent correlate of state 3 rates while phospholipid
      contents were correlated with state 4 rates. As the % poly-unsaturation and the %
      20:4n-6 in mitochondrial phospholipids were equivalent in toads and rats, and
      exceeded the levels in lizards, they may contribute to the inter-specific
      differences in oxidative capacities. We suggest that the numbers of CCO and ANT
      together with the poly-unsaturation of phospholipids explain the higher oxidative
      capacities in muscle mitochondria from rats and cane toads.

PMID- 16085441
TI  - Staphylococcus capitis endocarditis due to a transvenous endocardial pacemaker
      infection: case report and review of Staphylococcus capitis endocarditis.
AB  - OBJECTIVES: Newer microbiologic methods to determine the species of coagulase
      negative staphylococci (CoNS) have evolved which have shown that most
      endocarditis due to CoNS is caused by Staphylococcus epidermidis, and far fewer
      by Staphylococcus warneri and Staphylococcus lugdunensis. METHODS: The recent
      opportunity to successfully treat a patient with methicillin-resistant
      Staphylococcus capitis endocarditis secondary to an infected transvenous
      pacemaker led to a review of the literature relating to S. capitis endocarditis.
      RESULTS: Thirteen previously recorded patients were identified. Twelve (86%)
      patients were male. Ten had endocarditis associated with a native valve, two with
      prosthetic valves and one with a transvenous pacemaker. Mortality was low in all
      14 cases (including this case report) with only two deaths; one in a patient with
      a native valve and the other with a prosthetic valve. Four of the isolates were
      methicillin resistant but sensitive to vancomycin, which was used in the
      treatment of eight patients. Those patients with prosthetic cardiac devices
      appear to do better when the devices are surgically removed. CONCLUSIONS: CoNS as
      a cause of endocarditis appears to be increasing and the current ability to
      determine the species of these organisms should elicit the epidemiology, clinical
      characteristics and biomolecular mechanisms involved in the induction of valvular
      disease.

PMID- 16085442
TI  - Ochronotic rheumatism in Algeria: clinical, radiological, biological and
      molecular studies--a case study of 14 patients in 11 families.
AB  - OBJECTIVES: To confirm alkaptonuria and ochronotic arthropathy diagnosis by
      mutation screening of the homogentisate 1,2-dioxygenase (HGD) gene. Try to
      establish a genotype-phenotype correlation in the five subjects with a molecular
      study on HGD gene. METHODS: We report 14 alkaptonuria cases (10 men and four
      women) in 11 Algerian families. Consanguineous matings were evidenced in only
      three families (F = 1/16). Molecular analysis was performed by sequencing genomic
      DNA in order to identify the mutations of the HGD gene. RESULTS: Alkaptonuria was
      always confirmed by urinary homogentisic acid determination. Four different
      mutations of the HGD gene were found: an homozygous missense mutation,
      Serine189Isoleucine in two sisters with a mild phenotype; an homozygous splice
      site mutation (IVS1-1G > A) in a man with a severe phenotype (death at 61 years
      old from renal failure); a silent mutation, Alanine470Alanine at the heterozygous
      state in a man with a mild phenotype; a 'G' deletion at the position c.819 which
      causes a frameshift after Gly217(Gly217fs) that runs into a stop codon at c. 850.
      This mutation is novel and was found in heterozygosis in a woman with a mild
      phenotype. CONCLUSIONS: The two homozygous mutations were associated,
      respectively, with a severe and a mild phenotype but no genotype-phenotype
      correlation could be found.

PMID- 16085443
TI  - Veillonella discitis. A case report.

PMID- 16085444
TI  - Necrobiotic xanthogranuloma with multiple myeloma. Case report and pathogenic
      hypotheses.

PMID- 16085445
TI  - Challenge-based instruction in biomedical engineering: a scalable method to
      increase the efficiency and effectiveness of teaching and learning in biomedical
      engineering.
AB  - Vanderbilt University, Northwestern University, the University of Texas and the
      Harvard/MIT Health Sciences Technology Program have collaborated since 1999 to
      develop means to improve bioengineering education. This effort, funded by the
      National Science Foundation as the VaNTH Engineering Research Center in
      Bioengineering Educational Technologies, has sought a synthesis of learning
      science, learning technology, assessment and the domains of bioengineering in
      order to improve learning by bioengineering students. Research has shown that
      bioengineering educational materials may be designed to emphasize challenges that
      engage the student and, when coupled with a learning cycle and appropriate
      technologies, can lead to improvements in instruction.

PMID- 16085446
TI  - Three-dimensional finite element modeling of ligaments: technical aspects.
AB  - The objective of this paper is to describe strategies for addressing technical
      aspects of the computational modeling of ligaments with the finite element (FE)
      method. Strategies for FE modeling of ligament mechanics are described,
      differentiating between whole-joint models and models of individual ligaments.
      Common approaches to obtain three-dimensional ligament geometry are reviewed,
      with an emphasis on techniques that rely on volumetric medical image data.
      Considerations for the three-dimensional constitutive modeling of ligaments are
      reviewed in the context of ligament composition and structure. A novel approach
      to apply in situ strain to FE models of ligaments is described, and test problems
      are presented that demonstrate the efficacy of the approach. Approaches for the
      verification and validation of ligament FE models are outlined. The paper
      concludes with a discussion of future research directions.

PMID- 16085447
TI  - Fulminant hepatic failure following halothane anaesthesia.
AB  - The forensic pathologist is responsible for determining the cause, manner and
      approximate time of death and injury. After recording the detailed description of
      the external and internal appearances, a short summary should be offered of the
      major positive findings and their relationship to the cause of death. In many
      cases this will be obvious, however when the findings are less clear-cut, or are
      multiple, then the alternatives should be discussed detailing the possible
      sequence of events and interpreting the findings in concluding the cause of
      death. It is essential to causally connect the autopsy findings to the cause of
      death. We present a case report wherein a person who sustained avulsion injury to
      his left hand in an industrial accident, died due to, fulminant hepatitis,
      hepatic encephalopathy and acute renal failure, having undergone six operations
      under general anesthesia with halothane during his stay in the hospital.

PMID- 16085448
TI  - Obesity: the role of hypothalamic AMP-activated protein kinase in body weight
      regulation.
AB  - Obesity is rapidly increasing and is of great public health concern worldwide.
      Although there have been remarkable developments in obesity research over the
      past 10 years, the molecular mechanism of obesity is still not completely
      understood. Body weight results from the balance between food intake and energy
      expenditure. Recent studies have found that hypothalamic AMP-activated protein
      kinase plays a key role in regulating these processes. Leptin, insulin, glucose
      and alpha-lipoic acid have been shown to reduce food intake by lowering
      hypothalamic AMP-activated protein kinase activity, whereas ghrelin and glucose
      depletion increase food intake by increasing hypothalamic AMP-activated protein
      kinase activity. In addition, this enzyme plays a role in the central regulation
      of energy expenditure. These findings indicate that hypothalamic AMP-activated
      protein kinase is an important signal molecule, which integrates nutritional and
      hormonal signals and modulates feeding behavior and energy expenditure.

PMID- 16085449
TI  - Chloroplast outer membrane protein targeting and insertion.
AB  - Proteins in the chloroplast outer envelope membrane are nuclear encoded and post
      translationally targeted to the chloroplast. The targeting and membrane insertion
      of these proteins is not well understood. Although early work suggested
      otherwise, the best-studied outer membrane proteins (OMPs) use both proteins
      within the chloroplast and NTPs for insertion. There have been conflicting
      reports in the field regarding protein targeting and insertion, which have
      probably arisen because of differences in experimental methodology and different
      interpretations of reduction (versus abolition) of integration. This review
      summarizes what is known to date about the mechanism of chloroplast OMP
      targeting.

PMID- 16085450
TI  - Computational models of collective behavior.
AB  - Computational models of human collective behavior offer promise in providing
      quantitative and empirically verifiable accounts of how individual decisions lead
      to the emergence of group-level organizations. Agent-based models (ABMs) describe
      interactions among individual agents and their environment, and provide a process
      oriented alternative to descriptive mathematical models. Recent ABMs provide
      compelling accounts of group pattern formation, contagion and cooperation, and
      can be used to predict, manipulate and improve upon collective behavior. ABMs
      overcome an assumption that underlies much of cognitive science--that the
      individual is the crucial unit of cognition. The alternative advocated here is
      that individuals participate in collective organizations that they might not
      understand or even perceive, and that these organizations affect and are affected
      by individual behavior.

PMID- 16085451
TI  - Essential prerequisites to the safe and effective widespread roll-out of e
      working in healthcare.
AB  - Health informatics applications are advocated in many setting in many countries,
      with convincing logic as to their likely benefits. But at present these visions
      are being projected to rapid enforced implementation without the necessary
      foundations of: empirical evidence, beta piloting or replication studies,
      appreciation of the magnitude of change for health professionals and systems in
      electronic working compared to paper-based systems. This is creating legal and
      ethical risks that are largely avoidable, all for lack of post-piloting study and
      adequate evidence-based preparation. Instead, roll-out should be facilitated by
      developing good implementation practice based on empirical evidence from beta
      sites, to cover the following aspects: evidence, evaluation, equipment,
      education, empowerment. e-Working is an essential technology to support modern
      healthcare delivery. It needs to be as evidence-based as any other health care
      technology, but at present policy and parsimony are forcing it to fall short of
      these standards, thus generating unethical risks.

PMID- 16085452
TI  - Visualizing nursing workforce distribution: policy evaluation using geographic
      information systems.
AB  - Health services literature suggests that geographic information systems (GIS) are
      useful policy evaluation tools when policy success is dependent on location.
      Nursing workforce distribution is an inherently local issue and nursing shortages
      present serious concerns for local, state and national governments. In 1991,
      Missouri enacted a nurse recruitment and retention policy targeting underserved
      (HPSA-designated) counties. Following Institutional Review Board approval, policy
      effectiveness was explored using a combination of GIS data visualization, spatial
      and classic statistics. Results of both data visualization and statistical
      methods do not demonstrate an expected trend of decreasing group differences
      between HPSA and non-HPSA-designated counties over time. Only two of the five
      time periods studied had significant group differences. Between 1993 and 1995,
      the loss in nurse to population ratios in HPSA counties was significant (U=1020,
      p<0.001); however, between 1999 and 2001, the growth in nurse to population ratio
      changes in HPSA counties was significant (U=1032, p=0.001). The GIS data
      visualization and statistical techniques performed suggest that current policy
      definitions of underserved areas may not be effective in defining areas of
      nursing shortages and the existing policy implementation may not be achieving the
      stated goals.

PMID- 16085453
TI  - Distributed modules for text annotation and IE applied to the biomedical domain.
AB  - Biological databases contain facts from scientific literature that have been
      curated by hand to ensure high quality. Curation is time-consuming and can be
      supported by information extraction methods. We present a server software
      infrastructure which allows to easily plug in modules to identify biologically
      interesting pieces of text to be then presented in a web interface to the
      curator. There are modules which identify UniProt, UMLS and GO terminology, gene
      and protein names, mutations and protein-protein interactions. UniProt, UMLS and
      GO concepts are automatically linked to the original source. The module for
      mutations is based on syntax patterns and the one for protein-protein
      interactions relies on chunk parsing. All modules work as separate servers
      possibly distributed on different machines and can be combined into processing
      pipelines as necessary. Communication is based on XML annotated text streams,
      each server processing the XML elements it is designed for, and possibly adding
      more information in the form of XML annotation. The server and the underlying
      software are available to the public.

PMID- 16085454
TI  - The significance of cognitive modeling in building healthcare interfaces.
AB  - BACKGROUND: Although there are many reasons that widespread adoption of
      healthcare information systems has not transpired, one reason is a failure to
      take into account the cognitive needs of the users. AIM: To understand the
      cognitive needs of nurses and physicians and determine how these needs should
      influence the design of healthcare interfaces. DESIGN OF STUDY: A qualitative and
      quantitative study that compares how nurses and physicians comprehend patient
      information. SETTING: Twenty-four registered nurses and twenty-four physicians
      working in the specialties of gastrointestinal or internal medicine. METHODS:
      Each clinician reviewed two mock electronic medical records and summarized the
      cases using a think-aloud protocol. All verbalizations were coded for medical and
      conceptual information. RESULTS: The nurses included a larger mean proportion
      (p<0.001) of recalls than did the physicians. As compared to the nurses, the
      physicians included a statistically significant (p<0.001) larger mean proportion
      of inferences, conditional statements, and interventions. The nurses concentrated
      on functional problems, whereas the physicians focused on diagnosis, treatment,
      and management. CONCLUSION: The main cognitive differences between the physicians
      and the nurses are explained through the differences in their practice models.
      Therefore, healthcare IT must develop separate interfaces for each discipline to
      address their unique needs.

PMID- 16085455
TI  - The peroxisome proliferator-activated receptor-gamma agonist, pioglitazone,
      inhibits fat accumulation and fibrosis in the livers of rats fed a choline
      deficient, l-amino acid-defined diet.
AB  - Administration of a choline-deficient, l-amino acid-defined (CDAA) diet to rats
      causes steatohepatitis, hepatic fibrosis, and hepatocellular carcinoma, a
      pathology similar to that observed in non-alcoholic steatohepatitis (NASH). The
      aim of this study was to evaluate if a peroxisome proliferator-activated receptor
      (PPAR)-gamma agonist, pioglitazone (PGZ), could ameliorate CDAA diet-induced
      fatty liver and cirrhosis. Rats were fed a CDAA diet for 1 week and were given
      the CDAA diet for an additional week with or without PGZ (2-week model). Also,
      after administration of the CDAA diet for 12 weeks, rats were administered the
      CDAA diet for an additional 4 weeks with or without PGZ (16-week model). The CDAA
      diet, administered for either one or 12 weeks, induced fatty liver or cirrhosis
      with up-regulation of hepatic PPAR-gamma expression, respectively. In the 2-week
      model, rats treated with PGZ for 1 week demonstrated significantly lower hepatic
      triglyceride content and serum levels of tumor necrosis factor-alpha. In the 16
      week model, treatment for 4 weeks with PGZ ameliorated hepatic fibrosis with a
      decrease in the expression of procollagen, alpha-smooth muscle actin, and
      transforming growth factor-beta1 in comparison to rats without PGZ. These results
      suggest that PPAR-gamma agonist is a potential therapeutic modality to treat
      NASH.

PMID- 16085456
TI  - Impaired left ventricular relaxation in type 2 diabetic rats is related to
      myocardial accumulation of N(epsilon)-(carboxymethyl) lysine.
AB  - Myocardial dysfunction in the absence of myocardial ischemia is frequent in
      patients with diabetes mellitus but the underlying pathomechanism is unclear. We
      investigated whether accumulation of advanced glycation end products (AGEs) in
      the diabetic myocardium is related to its functional abnormalities. In 11 male
      homozygous Zucker diabetic fatty rats (ZDF/Gmi-fa/fa) aged 37 weeks (OBESE) and
      11 non-obese, non-diabetic littermates (LEAN), we measured left ventricular
      function (pressure-volume catheter) and levels of N(epsilon)-(carboxymethyl)
      lysine (CML), a prototypical AGE, in serum and the left ventricle (competitive
      enzyme linked immuno-assay). Overt diabetes mellitus (HbA1c > 9%) was present in
      all OBESE animals but not in LEAN. Systolic left ventricular function was not
      different between the groups, but the markers of left ventricular relaxation,
      dP/dt(min) and the relaxation constant tau, were impaired in OBESE. In parallel,
      CML levels were increased in serum (273 +/- 15 vs. 197 +/- 10 ng/ml, p<0.05) and
      in the left ventricle (18.4 +/- 1.1 vs. 12.5 +/- 2.0 ng/mg protein, p < 0.05) in
      OBESE compared to LEAN. There was a linear correlation between tau and the left
      ventricular CML levels (r = 0.65; p < 0.05). We conclude that type 2 diabetes is
      associated with predominant left ventricular diastolic dysfunction. Myocardial
      accumulation of advanced glycation end products may contribute to relaxation
      abnormalities in type 2 diabetes.

PMID- 16085457
TI  - Development of transgenic tobacco plants overexpressing maize glutathione S
      transferase I for chloroacetanilide herbicides phytoremediation.
AB  - Glutathione S-transferases (GSTs, EC 2.5.1.18) are a multigene family of
      detoxification enzymes that biotransform a wide variety of endogenous and
      exogenous electrophilic substrates, including herbicides. The isozyme GST I from
      maize exhibits significant catalytic activity for the chloroacetanilide herbicide
      alachlor and appears to be involved in its detoxifying process. To establish the
      in planta ability of GST I to detoxify from alachlor, transgenesis studies were
      carried out. The gene gstI-6His, which encodes for 6His-tagged GST I, was used
      for the construction of a binary vector suitable for genetic engineering of
      tobacco plants (Nicotiana tabacum). Through biolistic method transgenic tobacco
      plants were obtained. Integration of gstI-6His gene in transgenic tobacco plants
      genome was confirmed by polymerase chain reaction and Southern blot
      hybridization. The expression of active GST I was established by Western blot
      analysis, using anti-6His antibody, and by direct purification of 6-His tagged
      GST I on Ni-NTA agarose. Primary transformed plants harboring the gstI-6His gene
      were transferred to MS medium supplemented with alachlor and their phenotype was
      evaluated. The transgenic plants showed substantially higher tolerance to
      alachlor compared to non-transgenic plants in terms of root, leaves and vigorous
      development. These transgenic plants are potentially useful biotechnological
      tools for the development of phytoremediation system for the degradation of
      herbicide pollutants in agricultural fields.

PMID- 16085458
TI  - Gender differences in the presentation of subjects with restless legs syndrome.
AB  - BACKGROUND AND PURPOSE: To better understand the origin of the disproportionate
      number of women in previous treatment studies of patients with restless legs
      syndrome (RLS). PATIENTS AND METHODS: We conducted a survey in a self-selected
      group of patients who responded to print and radio recruiting advertisements
      regarding a clinical trial for RLS. Subjects completed a questionnaire which
      solicited information on presenting features of RLS, sleep-related symptoms, co
      morbidities and family history. RESULTS: A total of 158 (63% female) subjects
      with a mean age of 49 (+/-16) years fulfilled the criteria for putative diagnosis
      of RLS and participated in the study. There was no gender bias as far as duration
      of RLS, incidence of family history, number of affected days per week, or
      severity of daytime sleepiness was concerned. There was a subtle gender bias in
      sleep-related symptoms (involuntary movements when awake, sleep onset
      difficulties and frequent wakings at night) where a disproportionately high
      number of women subjects presented with all three symptoms. For any one symptom,
      or any pair of symptoms, there were no gender differences. Women also were more
      likely to present with co-existent hypothyroidism. Both male and female subjects
      were more likely to recall female relatives affected with RLS. CONCLUSIONS:
      Gender differences associated with symptom load, co-morbidities of RLS and
      possible patterns of inheritance may contribute to increased numbers of women
      presenting for treatment of RLS.

PMID- 16085459
TI  - Global sleep dissatisfaction for the assessment of insomnia severity in the
      general population of Portugal.
AB  - BACKGROUND AND PURPOSE: This study examines the prevalence and associated factors
      of insomnia symptoms and sleep dissatisfaction in the general population of
      Portugal. PATIENTS AND METHODS: We interviewed by telephone 1858 participants
      aged 18 years or older and representative of the general population of Portugal
      using the Sleep-EVAL system. Participation rate was 83%. The questionnaire
      included the assessment of sleep habits, insomnia symptomatology according to DSM
      IV and ICSD classifications, associated and sleep/mental disorders and daytime
      consequences. RESULTS: Insomnia symptoms occurring at least 3 nights per week
      were reported by 28.1% of the sample and global sleep dissatisfaction (GSD) by
      10.1%. Difficulty maintaining sleep was the most frequent symptom (21.0%); 29.4%
      of subjects with insomnia symptoms reported GSD. Daytime consequences, medical
      consultations for sleep and use of sleep medication were at least 2 times more
      frequent among subjects with insomnia symptoms and GSD compared to subjects with
      insomnia symptoms without GSD; insomnia diagnoses were also more frequent in the
      GSD group. CONCLUSIONS: The results show a severity gradation among subjects with
      only 1 insomnia symptom, those with 2 or 3 insomnia symptoms but without GSD and
      those with at least 1 insomnia symptom and GSD. Specific sleep or psychiatric
      disorders were identified for the majority of GSD subjects (86%); this rate
      dropped to 50.6% when only 1 insomnia symptom without GSD was reported. GSD
      appeared to be a good indicator of the presence of a sleep or psychiatric
      disorder and a good discriminator of the severity of sleep disturbances among
      subjects with insomnia symptoms.

PMID- 16085460
TI  - The lived experience post-autologous haemopoietic stem cell transplant (HSCT): a
      phenomenological study.

PMID- 16085461
TI  - Splicing intervention for Duchenne muscular dystrophy.
AB  - The manipulation of pre-mRNA to alter gene transcript splicing patterns offers
      considerable potential for many genetic disorders. In particular, the targeted
      removal of one or more exons from a gene transcript can skip over, or compensate
      for, disease-causing mutations. Duchenne muscular dystrophy (DMD), the most
      common and severe form of muscular dystrophy, is one such disorder that could
      benefit from this strategy. Splicing modulation can convert a DMD phenotype into
      the less severe allelic Becker-like phenotype. Recent studies using antisense
      oligonucleotide-targeted exon skipping to induce near normal dystrophin in vivo
      in animal models, and in vitro in DMD cell lines, highlight the promise of this
      approach. On the basis of these successes, human clinical trials could be
      realized in the near future.

PMID- 16085462
TI  - Emerging therapies for polycystic kidney disease.
AB  - Polycystic kidney diseases are the most common, monogenetic, inherited diseases
      in humans. Numerous human genes or gene loci are associated with a renal cystic
      phenotype. Currently, there are no treatments available to slow the development
      of renal cystic pathology; however, animal studies have identified several
      potential approaches to intervene in the disease process. The most advanced
      therapy is the use of vasopressin V(2) receptor antagonists, which reduce renal
      cAMP, a known promoter of renal cystic enlargement. Other therapies under study
      include the use of c-myc antisense oligonucleotides and epidermal growth factor
      receptor tyrosine kinase inhibitors. Considering the diverse genes that cause
      renal cysts and the multiorgan involvement of these diseases, multiple
      therapeutic approaches will eventually be necessary to treat these diseases.

PMID- 16085463
TI  - Oncolytic adenovirus expressing a p53 variant resistant to degradation by HPV E6
      protein exhibits potent and selective replication in cervical cancer.
AB  - Rationale in the development of novel treatment strategies for HPV-associated
      cancers is targeting on the basis of the presence of HPV in (pre)malignant cells.
      Here, we designed a new conditionally replicating adenovirus (CRAd) for selective
      and effective oncolytic replication in HPV-containing cells. As the backbone, we
      used the CRAd AdCB016, which replicates selectively in cells expressing HPV E6
      and E7 proteins. To enhance its oncolytic potency, we armed AdCB016 with p53
      variant mp53(268N), which is resistant to HPV E6-mediated degradation. The new
      CRAd AdCB016-mp53(268N) was analyzed for its lytic replication properties in
      cervical carcinoma cell lines, HPV-immortalized keratinocyte cell lines
      representing dysplastic cells, and primary human keratinocytes. AdCB016
      mp53(268N) exhibited 10- to 1000-fold greater efficacy than AdCB016 on high-risk
      HPV-positive cervical carcinoma cells and HPV-immortalized keratinocytes.
      Importantly, infection with AdCB016-mp53(268N) did not affect primary
      nonmalignant human keratinocytes. This favorable efficacy and safety profile was
      confirmed in organotypic raft cultures. Our findings suggest that AdCB016
      mp53(268N) is a promising new agent for treatment of HPV-associated human
      cancers.

PMID- 16085464
TI  - Efficient hepatic delivery and expression from a recombinant adeno-associated
      virus 8 pseudotyped alpha1-antitrypsin vector.
AB  - alpha1-Antitrypsin (AAT) deficiency is a single-gene disorder in which a mutation
      in the AAT (approved symbol SERPINA1) gene (PI*Z) leads to misfolding of the
      protein, loss of the protective antiprotease effect of AAT for the lungs, and a
      toxic effect on hepatocytes. Optimal therapy for AAT deficiency will require a
      high percentage of hepatocyte transduction to be effective for liver and lung
      disease. Recently, rAAV genomes pseudotyped with capsids from serotypes 7 and 8
      showed efficient hepatic transduction. We hypothesized that upon portal vein
      injection to target hepatocytes, serotype 8 would better transduce target cells
      and therefore express hAAT in both a greater percentage of cells and greater
      amounts. AAV2 and pseudotyped vectors for serotypes 1, 5, and 8 carrying the
      human AAT transgene were injected at 1 x 10(10) particle doses into C57Bl/6 mice.
      Circulating hAAT from AAV2/8-injected animals showed a 2-log advantage over AAV2
      and 3-log increase over AAV2/1 and 5 for the 24-week study. Most significantly,
      up to 40% of total liver cells stained positive for the transgene in AAV2/8
      subjects while remaining primarily episomal. Therefore, pseudotyped AAV8 provides
      a vehicle to infect a high percentage of hepatocytes stably and thereby express
      therapeutic molecules to modify AAT PiZ transcripts.

PMID- 16085465
TI  - Ischemic heart disease in renal transplant candidates: towards non-invasive
      approaches for preoperative risk stratification.
AB  - This editorial refers to the paper of R. Sharma et al. entitled "Dobutamine
      stress echocardiography and cardiac troponin T for the detection of significant
      coronary artery disease and predicting outcome in renal transplant candidates".
      The editorial discusses different strategies for cardiac risk assessment in
      patients with end-stage renal disease undergoing renal transplantation.

PMID- 16085466
TI  - Overview of recruitment for the osteoporotic fractures in men study (MrOS).
AB  - Large, long term research studies present recruitment challenges that can be met
      with collaborative approaches to identify and enroll participants. The
      Osteoporotic Fractures in Men Study (MrOS), a multi-center observational study
      designed to determine risk factors for osteoporosis, fractures and prostate
      cancer in older men, recruited 5995 participants over a 25-month period.
      Enrolling a cohort that represented the race and age distribution of each
      community, and developing interest in an older male cohort about a condition
      commonly thought of as a "women's disease," were major recruitment challenges.
      During the start-up phase, recruitment challenges and strategies were analyzed
      and collective approaches were developed to address ways to motivate the target
      population. Key methods included mailings using community and provider contact
      lists; regional and senior newspaper advertisements; and presentations targeted
      to seniors. Sites used a centrally developed recruitment brochure. Response to
      mass mailings at some sites surpassed 10-15% and appointment show rates averaged
      above 85%. The final number enrolled in MrOS was 5% more than the original
      recruitment goal of 5700. Minority recruitment was enhanced through the use of
      the Health Care Financing Administration and other databases that allowed for
      targeted recruitment. Overall, minority enrollment was approximately 10.56% of
      the cohort (244 African American, 191 Asian). Men age>80 were enthusiastic and
      represent about 18% of enrollees. Through a coordinated approach of developing
      and refining recruitment strategies and materials, sites were able to adapt their
      original strategies and complete recruitment ahead of schedule.

PMID- 16085467
TI  - The evolution of late life.
AB  - Late life is a distinct phase of life characterized by a cessation in the
      deterioration of survivorship and fecundity characteristic of normal aging.
      Several theories have been proposed to explain non-aging at late ages,
      specifically with regards to late-life mortality-rate plateaus. All such theories
      must be compatible with formal evolutionary theory and experimental findings.
      Here, we develop a critique of theories of late life based on evolutionary
      biology.

PMID- 16085468
TI  - The mechanism of base excision repair in Chlamydiophila pneumoniae.
AB  - Repair of damaged DNA is of great importance in maintaining genome integrity, and
      there are several pathways for repair of damaged DNA in almost all organisms.
      Base excision repair (BER) is a main process for repairing DNA carrying slightly
      damaged bases. Several proteins are required for BER; these include DNA
      glycosylases, AP endonuclease, DNA polymerase, and DNA ligase. In some bacteria
      the single-stranded specific exonuclease, RecJ, is also involved in BER. In this
      research, six Chlamydiophila pneumoniae (C. pneumoniae) genes, encoding uracil
      DNA glycosylase (CpUDG), endonuclease IV (CpEndoIV), DNA polymerase I
      (CpDNApolI), endonuclease III (CpEndoIII), single-stranded specific exonuclease
      RecJ (CpRecJ), and DNA ligase (CpDNALig), were inserted into the expression
      vector pET28a. All proteins, except for CpDNALig, were successfully expressed in
      E. coli, and purified proteins were characterized in vitro. C. pneumoniae BER was
      reconstituted in vitro with CpUDG, CpEndoIV, CpDNApolI and E. coli DNA ligase
      (EcDNALig). After uracil removal by CpUDG, the AP site could be repaired by two
      BER pathways that involved in the replacement of either one (short patch BER) or
      multiple nucleotides (long patch BER) at the lesion site. CpEndoIII promoted
      short patch BER via its 5'-deoxyribophosphodiesterase (5'-dRPase) activity, while
      CpRecJ had little effect on short patch BER. The flap structure generated during
      DNA extension could be removed by the 5'-exonuclease activity of CpDNApolI. Based
      on these observations, we propose a probable mechanism for BER in C. pneumoniae.

PMID- 16085469
TI  - Estimation of pK(a) values using microchip capillary electrophoresis and indirect
      fluorescence detection.
AB  - Microchip capillary electrophoresis (CE), coupled with indirect fluorescence
      detection was investigated for estimating the pK(a) values of non-fluorescent
      compounds. The CE method is based on the differences in electrophoretic mobility
      of the analyte as a function of the pH of the running buffer. Nine compounds were
      tested, including several of pharmaceutical importance, with pK(a) values from
      10.3 to 4.6. All buffers contained 5-TAMRA as the fluorescent probe for indirect
      detection. Calculated pK(a) values agreed well with literature values obtained by
      traditional methods, differing not more than 0.2 from the literature value. The
      current work on single lane chips demonstrates the principle of microchip CE with
      indirect detection as a viable method for estimating pK(a) values. However,
      increased throughput will be required using a multilane chip to enable the
      approach to be used practically.

PMID- 16085470
TI  - Calorimetric and spectroscopic investigations of the thermal denaturation of wild
      type nitrite reductase.
AB  - Nitrite reductase (NiR) is a multicopper protein, with a trimeric structure
      containing two types of copper site: type 1 is present in each subunit whereas
      type 2 is localized at the subunits interface. The paper reports on the thermal
      behaviour of wild type NiR from Alcaligenes faecalis S-6. The temperature-induced
      changes of the copper centres are characterized by optical spectroscopy and
      electron paramagnetic resonance spectroscopy, and by establishing the thermal
      stability by differential scanning calorimetry. The calorimetric profile of the
      enzyme shows a single endothermic peak with maximum heat absorption at T(m)
      approximately 100 degrees C, revealing an exceptional thermal stability. The
      thermal transition is irreversible and the scan rate dependence of the
      calorimetric trace indicates that the denaturation of NiR is kinetically
      controlled. The divergence of the activation energy values determined by
      different methods is used as a criterion for the inapplicability of the one-step
      irreversible model. The best fit of the DSC profiles is obtained when the
      classical Lumry-Eyring model, N<-->U-->F, is considered. The simulation results
      indicate that the irreversible step prevails on the reversible one. Moreover, it
      is found that the conformational changes within the type-1 copper environments
      precede the denaturation of the whole protein. No evidence of protein
      dissociation within the temperature range investigated was observed.

PMID- 16085471
TI  - Is adjuvant therapy with three-dimensional conformal irradiation combined with
      capecitabine (Xeloda) for gastric cancer effective?

PMID- 16085472
TI  - Increased expression of interleukin-6 by vasoactive intestinal peptide is
      associated with regulation of CREB, AP-1 and C/EBP, but not NF-kappaB, in mouse
      calvarial osteoblasts.
AB  - Interleukin-6 (IL-6), and the related cytokines IL-11, leukemia inhibitory factor
      (LIF) and oncostatin M (OSM), are potent stimulators of osteoclastic bone
      resorption. In the present study, we have addressed the possibility that the
      neuropeptide vasoactive intestinal peptide (VIP) may regulate the production of
      and/or sensitivity to the IL-6 family of cytokines in mouse calvarial
      osteoblasts. VIP stimulated IL-6 mRNA expression and protein release in a time-
      and concentration-dependent manner, whereas mRNA expression of the IL-6 receptor,
      as well as mRNA expressions of IL-11, LIF, OSM and their cognate receptors, were
      unaffected by VIP. In cells transfected with the IL-6 promoter coupled to
      luciferase, VIP increased transcriptional activity. The effects of VIP were
      shared by the related neuropeptide PACAP-38, belonging to the same superfamily of
      neuropeptides, whereas secretin did not have any effect, indicating that the
      effects were mediated by VPAC2 receptors. The effects of VIP were potentiated by
      the cyclic AMP phosphodiesterase inhibitor rolipram and mimicked by forskolin,
      indicating the involvement of the cyclic AMP/protein kinase A pathway. This was
      further demonstrated by the facts that the stimulatory effect of VIP on
      luciferase activity could be reversed by the PKA inhibitors H-89 and KT5720 and
      was mimicked by cyclic AMP analogues selective for PKA, but not by those
      selective for Epac. In addition, VIP enhanced the phosphorylation of CREB, as
      assessed by both immunocytochemical analysis and Western blot. The DNA binding
      activity of nuclear extracts to C/EBP was increased by VIP, whereas binding to AP
      1 was decreased. In contrast, DNA binding to NF-kappaB, as well as nuclear
      translocation of NF-kappaB and C/EBP, were unaffected by VIP. The mRNA
      expressions of C/EBPbeta, C/EBPdelta, C/EBPgamma, c-Jun, JunB, c-Fos, Fra-1 and
      IkappaBalpha and protein level of IkappaBalpha were all unaffected by VIP. These
      observations, together, demonstrate that VIP stimulates IL-6 production in
      osteoblasts by a mechanism likely to be mediated by VPAC2 receptors and dependent
      on cyclic AMP/protein kinase A/CREB activation and also involving the
      transcription factors C/EBP and AP-1.

PMID- 16085473
TI  - The inflammasome.

PMID- 16085474
TI  - T regulatory cells.

PMID- 16085475
TI  - The vestibular system.

PMID- 16085476
TI  - DDT resistance in flies carries no cost.

PMID- 16085477
TI  - Evolution of the extinct Sabretooths and the American cheetah-like cat.

PMID- 16085478
TI  - Asymmetric division: a kinesin for spindle positioning.
AB  - The meiotic spindles of animal eggs move to extremely asymmetric positions, close
      to the cell cortex. A recent paper has identified a motor complex that may move
      the meiotic spindle toward the cortex in Caenorhabditis elegans eggs.

PMID- 16085479
TI  - Guard cells: transcription factors regulate stomatal movements.
AB  - Recent work shows that transcription factors are necessary for stomatal movements
      in plants. Different members of the plant-specific R2R3-MYB transcription factor
      family are required for mediating stomatal opening in response to light and
      stomatal closure in response to darkness.

PMID- 16085480
TI  - Division-plane positioning: microtubules strike back.
AB  - Two groups have recently developed physical techniques to manipulate the position
      of the nucleus in fission yeast. Their studies reveal how microtubules confine
      the nucleus to the cell center, and indicate how the position of the cleavage
      plane during cell division is coordinated with that of the nucleus.

PMID- 16085481
TI  - Ecology: linking species diversity and genetic diversity.
AB  - Although there is a great deal of interest in the biological diversity of species
      and of genes, it is only recently that researchers have begun to investigate the
      processes that exert parallel influences on these different levels of diversity.

PMID- 16085482
TI  - Swarming motility: it better be wet.
AB  - When grown on a soft agar surface in a rich medium, cells of Salmonella
      typhimurium elongate, produce extra flagella and move over the surface in a
      coordinated manner. In mutants with defects in the chemotaxis signaling pathway,
      the agar plates remain dry and the cells' flagella are short. Recent work shows
      that the anti-sigma factor controlling late-gene flagellar synthesis is secreted
      less by flagella when things are dry: the flagellum senses wetness.

PMID- 16085483
TI  - Germ cells: sex and repression in mice.
AB  - The mouse Blimp1 gene encodes a transcriptional repressor that is essential for B
      cell development. Recent studies have shown that the Blimp1 protein also plays a
      critical role in the specification of mouse primordial germ cells.

PMID- 16085484
TI  - MicroRNAs: Loquacious speaks out.
AB  - In Drosophila, Dicer-2 requires the double-stranded RNA binding protein R2D2, to
      mediate the assembly of short interfering RNAs into the RNA-induced silencing
      complex. New data show that Dicer-1 also requires a double-stranded RNA binding
      protein called Loquacious for efficient microRNA-mediated gene silencing.

PMID- 16085485
TI  - Cell division: SIN, cytokinesis and ethanol dependency.
AB  - A novel mutant screen in fission yeast has identified the 'ethanol dependent'
      protein etd1p as a potential link between the septation initiation network (SIN),
      which initiates cytokinesis, and the actomyosin contractile ring that drives
      separation of the two daughter cells at the end of mitosis.

PMID- 16085486
TI  - Sox9 is essential for outer root sheath differentiation and the formation of the
      hair stem cell compartment.
AB  - BACKGROUND: The mammalian hair represents an unparalleled model system to
      understand both developmental processes and stem cell biology. The hair follicle
      consists of several concentric epithelial sheaths with the outer root sheath
      (ORS) forming the outermost layer. Functionally, the ORS has been implicated in
      the migration of hair stem cells from the stem cell niche toward the hair bulb.
      However, factors required for the differentiation of this critical cell lineage
      remain to be identified. Here, we describe an unexpected role of the HMG-box
      containing gene Sox9 in hair development. RESULTS: Sox9 expression can be first
      detected in the epithelial component of the hair placode but then becomes
      restricted to the outer root sheath (ORS) and the hair stem cell compartment
      (bulge). Using tissue-specific inactivation of Sox9, we demonstrate that this
      gene serves a crucial role in hair differentiation and that skin deleted for Sox9
      lacks external hair. Strikingly, the ORS acquires epidermal characteristics with
      ectopic expression of GATA3. Moreover, Sox9 knock hair show severe proliferative
      defects and the stem cell niche never forms. Finally, we show that Sox9
      expression depends on sonic hedgehog (Shh) signaling and demonstrate
      overexpression in skin tumors in mouse and man. CONCLUSIONS: We conclude that
      although Sox9 is dispensable for hair induction, it directs differentiation of
      the ORS and is required for the formation of the hair stem cell compartment. Our
      genetic analysis places Sox9 in a molecular cascade downstream of sonic hedgehog
      and suggests that this gene is involved in basal cell carcinoma.

PMID- 16085487
TI  - Temperature synchronization of the Drosophila circadian clock.
AB  - BACKGROUND: Circadian clocks are synchronized by both light:dark cycles and by
      temperature fluctuations. Although it has long been known that temperature cycles
      can robustly entrain Drosophila locomotor rhythms, nothing is known about the
      molecular mechanisms involved. RESULTS: We show here that temperature cycles
      induce synchronized behavioral rhythms and oscillations of the clock proteins
      PERIOD and TIMELESS in constant light, a situation that normally leads to
      molecular and behavioral arrhythmicity. We show that expression of the Drosophila
      clock gene period can be entrained by temperature cycles in cultured body parts
      and isolated brains. Further, we show that the phospholipase C encoded by the
      norpA gene contributes to thermal entrainment, suggesting that a receptor-coupled
      transduction cascade signals temperature changes to the circadian clock. We
      initiated the further genetic dissection of temperature-entrainment and isolated
      the novel Drosophila mutation nocte, which is defective in molecular and
      behavioral entrainment by temperature cycles but synchronizes normally to
      light:dark cycles. CONCLUSIONS: We conclude that temperature synchronization of
      the circadian clock is a tissue-autonomous process that is able to override the
      arrhythmia-inducing effects of constant light. Our data suggest that it involves
      a cell-autonomous signal-transduction cascade from a thermal receptor to the
      circadian clock. This process includes the function of phospholipase C and the
      product specified by the novel mutation nocte.

PMID- 16085488
TI  - Saccharomyces cerevisiae Rad9 acts as a Mec1 adaptor to allow Rad53 activation.
AB  - BACKGROUND: The DNA damage checkpoint is a protein kinase-based signaling system
      that detects and signals physical alterations in DNA. Despite having identified
      many components of this signaling cascade, the exact mechanisms by which
      checkpoint kinases are activated after DNA damage, as well as the role of the
      checkpoint mediators, remain poorly understood. RESULTS: To elucidate the
      mechanisms that underlie the MEC1 and RAD9-dependent activation of Rad53, the
      Saccharomyces cerevisiae ortholog of Chk2, we mapped and characterized in vivo
      phosphorylation sites present on Rad53 after DNA damage by mass spectrometry. We
      find that Rad53 requires for its activation multisite phosphorylation on a number
      of typical and atypical Mec1 phosphorylation sites, thus confirming that Rad53 is
      a direct target of Mec1, the mammalian ATR homolog. Moreover, by using
      biochemical reconstitution experiments, we demonstrate that efficient and direct
      phosphorylation of Rad53 by Mec1 is only observed in the presence of purified
      Rad9, the archetypal checkpoint mediator. We find that the stimulatory activity
      of Rad9 requires a phospho- and FHA-dependent interaction with Rad53, which
      allows Rad53 to be recognized as a substrate for Mec1. CONCLUSIONS: Our results
      indicate that Rad9 acts as a bona fide signaling adaptor that enables Rad53
      phosphorylation by Mec1. Given the high degree of conservation of checkpoint
      signaling in eukaryotes, we propose that one of the critical functions of
      checkpoint mediators such as MDC1, 53BP1, or Brca1 is to act as PIKK adaptors
      during the DNA damage response.

PMID- 16085489
TI  - The 14-3-3 protein rad24p modulates function of the cdc14p family phosphatase
      clp1p/flp1p in fission yeast.
AB  - Schizosaccharomyces pombe cells divide through the use of an actomyosin-based
      contractile ring. In response to perturbation of the actomyosin ring, S. pombe
      cells delay in a "cytokinesis-competent" state characterized by continuous repair
      and maintenance of the actomyosin ring and a G2 delay. This checkpoint mechanism
      requires the function of the Cdc14p-family phosphatase Clp1p/Flp1p and the
      septation initiation network (SIN). In response to cytokinetic defects, Clp1p,
      normally nucleolar in interphase, is retained in the cytoplasm until completion
      of cell division in a SIN-dependent manner. Here, we show that a phosphorylated
      form of Clp1p binds the 14-3-3 protein Rad24p and is retained in the cytoplasm in
      a Rad24p-dependent manner in response to cytokinesis defects. This physical
      interaction depends on the function of the SIN component, Sid2p. In the absence
      of Rad24p, cells are unable to maintain SIN signaling and lose viability upon
      mild cytokinetic stress. The requirement of Rad24p in this checkpoint is bypassed
      by ectopic activation of the SIN. Furthermore, SIN-dependent nuclear exclusion of
      Clp1p is dependent on Rad24p function. We conclude that Rad24p-mediated
      cytoplasmic retention of Clp1p/Flp1p is important for cell viability upon stress
      to the division apparatus.

PMID- 16085490
TI  - Distinct nuclear and cytoplasmic functions of the S. pombe Cdc14-like phosphatase
      Clp1p/Flp1p and a role for nuclear shuttling in its regulation.
AB  - Cdc14-like phosphatases regulate a variety of cell cycle events by
      dephosphorylating CDK sites. Their cell cycle-dependent changes in localization
      may be important to carry out distinct functions. Work in budding and fission
      yeast suggested that Cdc14-like phosphatases are inhibited by nucleolar
      sequestration. In S. cerevisiae, Cdc14p is released from the nucleolus by the
      FEAR network and Cdk1, whereas the S. pombe CDC14-like phosphatase Clp1p (also
      known as Flp1p) is released at mitotic entry by an unknown mechanism. The mitotic
      exit network (MEN) in S. cerevisiae and its homologous network, the septation
      initiation network (SIN), in S. pombe act through an unknown mechanism to keep
      the phosphatase out of the nucleolus in late mitosis. SIN-dependent cytoplasmic
      maintenance of Clp1p is thought to be essential for the cytokinesis checkpoint,
      which blocks further rounds of nuclear division until cytokinesis is completed.
      By targeting Clp1p to the nucleus or the cytoplasm, we demonstrate distinct
      functions for these pools of Clp1p in chromosome segregation and cytokinesis,
      respectively. Our results further suggest that the SIN does not keep Clp1p out of
      the nucleolus by regulating nucleolar affinity, as proposed for S. cerevisiae
      Cdc14p, but instead, Clp1p may be regulated by nuclear import/export.

PMID- 16085491
TI  - Vestibular reafference shapes voluntary movement.
AB  - The vestibular organs in the inner ear are commonly thought of as sensors that
      serve balance, gaze control, and higher spatial functions such as navigation.
      Here, we investigate their role in the online control of voluntary movements. The
      central nervous system uses sensory feedback information during movement to
      detect and correct errors as they develop. Vestibular organs signal three
      dimensional head rotations and translations and so could provide error
      information for body movements that transport the head in space. To test this, we
      electrically stimulated human vestibular nerves during a goal-directed voluntary
      tilt of the trunk. The stimulating current waveform was made identical to the
      angular velocity profile of the head in the roll plane. With this, we could
      proportionally increase or decrease the rate of vestibular nerve firing, as if
      the head were rotating faster or slower than it actually was. In comparison to
      movements performed without stimulation, subjects tilted their trunk faster and
      further or slower and less far, depending upon the polarity of the stimulus. The
      response was negligible when identical stimulus waveforms were replayed to
      stationary subjects. We conclude that the brain uses vestibular information for
      online error correction of planned body-movement trajectories.

PMID- 16085492
TI  - Homologous recombination rescues mismatch-repair-dependent cytotoxicity of S(N)1
      type methylating agents in S. cerevisiae.
AB  - Resistance of mammalian cells to S(N)1-type methylating agents such as N-methyl
      N'-nitro-N-nitrosoguanidine (MNNG) generally arises through increased expression
      of methylguanine methyltransferase (MGMT), which reverts the cytotoxic O(6)
      methylguanine ((Me)G) to guanine, or through inactivation of the mismatch repair
      (MMR) system, which triggers cell death through aberrant processing of (Me)G/T
      mispairs generated during DNA replication when MGMT capacity is exceeded. Given
      that MMR and (Me)G-detoxifying proteins are functionally conserved through
      evolution, and that MMR-deficient Escherichia coli dam(-) strains are also
      resistant to MNNG, the finding that MMR status did not affect the sensitivity of
      Saccharomyces cerevisiae to MNNG was unexpected. Because (Me)G residues in DNA
      trigger homologous recombination (HR), we wondered whether the efficient HR in S.
      cerevisiae might alleviate the cytotoxic effects of (Me)G processing. We now show
      that HR inactivation sensitizes S. cerevisiae to MNNG and that, as in human
      cells, defects in the MMR genes MLH1 and MSH2 rescue this sensitivity.
      Inactivation of the EXO1 gene, which encodes the only exonuclease implicated in
      MMR to date, failed to rescue the hypersensitivity, which implies that scExo1 is
      not involved in the processing of (Me)G residues by the S. cerevisiae MMR system.

PMID- 16085493
TI  - PIP2 hydrolysis and calcium release are required for cytokinesis in Drosophila
      spermatocytes.
AB  - The role of calcium (Ca(2+)) in cytokinesis is controversial, and the precise
      pathways that lead to its release during cleavage are not well understood. Ca(2+)
      is released from intracellular stores by binding of inositol trisphosphate (IP3)
      to the IP3 receptor (IP3R), yet no clear role in cytokinesis has been established
      for the precursor of IP3, phosphatidylinositol 4,5-bisphosphate (PIP2). Here,
      using transgenic flies expressing PLCdelta-PH-GFP, which specifically binds PIP2,
      we identify PIP2 in the plasma membrane and cleavage furrows of dividing
      Drosophila melanogaster spermatocytes, and we establish that this phospholipid is
      required for continued ingression but not for initiation of cytokinesis. In
      addition, by inhibiting phospholipase C, we show that PIP2 must be hydrolyzed to
      maintain cleavage furrow stability. Using an IP3R antagonist and a Ca(2+)
      chelator to examine the roles of IP3R and Ca(2+) in cytokinesis, we demonstrate
      that both of these factors are required for cleavage furrow stability, although
      Ca(2+) is dispensable for cleavage plane specification and initiation of
      furrowing. Strikingly, providing cells with Ca(2+) obviates the need to hydrolyze
      PIP2. Thus, PIP2, PIP2 hydrolysis, and Ca(2+) are required for the normal
      progression of cytokinesis in these cells.

PMID- 16085494
TI  - PtdIns(4,5)P2 functions at the cleavage furrow during cytokinesis.
AB  - Phosphoinositides play important roles in regulating the cytoskeleton and vesicle
      trafficking, potentially important processes at the cleavage furrow. However, it
      remains unclear which, if any, of the phosphoinositides play a role during
      cytokinesis. A systematic analysis to determine if any of the phosphoinositides
      might be present or of functional importance at the cleavage furrow has not been
      published. Several studies hint at a possible role for one or more
      phosphoinositides at the cleavage furrow. The best of these are genetic data
      identifying mutations in phosphoinositide-modifying enzymes (a PtdIns(4)P-5
      kinase in S. pombe and a PI-4-kinase in D. melanogaster) that interfere with
      cytokinesis. The genetic nature of these experiments leaves questions as to how
      direct may be their contribution to cytokinesis. Here we show that a single
      phosphoinositide, PtdIns(4,5)P2, specifically accumulates at the furrow.
      Interference with PtdIns(4,5)P2 interferes with adhesion of the plasma membrane
      to the contractile ring at the furrow. Finally, four distinct interventions to
      specifically interfere with PtdIns(4,5)P2 each impair cytokinesis. We conclude
      that PtdIns(4,5)P2 is present at the cleavage furrow and is required for normal
      cytokinesis at least in part because of a role in adhesion between the
      contractile ring and the plasma membrane.

PMID- 16085495
TI  - The homeobox transcription factor even-skipped regulates netrin-receptor
      expression to control dorsal motor-axon projections in Drosophila.
AB  - Homeobox transcription-factor codes control motor-neuron subtype identity and
      dorsal versus ventral axon guidance in both vertebrate and invertebrate nervous
      systems; however, the specific axon guidance-receptors that are regulated by
      these transcription factors to control pathfinding are poorly defined. In
      Drosophila, the Even-skipped (Eve) transcription factor specifies dorsal motor
      axon projection through the regulation of unidentified guidance molecules. The
      Netrins and their attractive and repulsive receptors DCC and Unc-5, respectively,
      define important conserved cue and receptor families that control growth-cone
      guidance. In Drosophila, the Netrins and frazzled (the fly homolog of DCC)
      contribute to motor-axon guidance. Here, using genetics and single-cell mRNA
      expression analysis, we show that expression and requirement of different Netrin
      receptor combinations correlate with distinct dorsal and ventral motor-axon
      projections in Drosophila. Mis-expression of eve dorsalizes ventral axons in part
      through the upregulation of Unc-5, whereas loss of eve function in two dorsally
      projecting motor neurons results in aberrant axon projections and a failure to
      express Unc-5. Our results support a functional link between the expression of
      distinct Netrin receptor combinations and the transcriptional control of dorsal
      motor-axon guidance.

PMID- 16085497
TI  - Evidence for a global Wolbachia replacement in Drosophila melanogaster.
AB  - Wolbachia are maternally inherited intracellular alpha-Proteobacteria found in
      numerous arthropod and filarial nematode species. They influence the biology of
      their hosts in many ways. In some cases, they act as obligate mutualists and are
      required for the normal development and reproduction of the host. They are best
      known, however, for the various reproductive parasitism traits that they can
      generate in infected hosts. These include cytoplasmic incompatibility (CI)
      between individuals of different infection status, the parthenogenetic production
      of females, the selective killing of male embryos, and the feminization of
      genetic males. Wolbachia infections of Drosophila melanogaster are extremely
      common in both wild populations and long-term laboratory stocks. Utilizing the
      newly completed genome sequence of Wolbachia pipientis wMel, we have identified a
      number of polymorphic markers that can be used to discriminate among five
      different Wolbachia variants within what was previously thought to be the single
      clonal infection of D. melanogaster. Analysis of long-term lab stocks together
      with wild-caught flies indicates that one of these variants has replaced the
      others globally within the last century. This is the first report of a global
      replacement of a Wolbachia strain in an insect host species. The sweep is at odds
      with current theory that cannot explain how Wolbachia can invade this host
      species given the observed cytoplasmic incompatibility characteristics of
      Wolbachia infections in D. melanogaster in the field.

PMID- 16085496
TI  - Cik1 targets the minus-end kinesin depolymerase kar3 to microtubule plus ends.
AB  - Kar3, a Saccharomyces cerevisiae Kinesin-14, is essential for karyogamy and
      meiosis I but also has specific functions during vegetative growth. For its
      various roles, Kar3 forms a heterodimer with either Cik1 or Vik1, both of which
      are noncatalytic polypeptides. Here, we present the first biochemical
      characterization of Kar3Cik1, the kinesin motor that is essential for karyogamy.
      Kar3Cik1 depolymerizes microtubules from the plus end and promotes robust minus
      end-directed microtubule gliding. Immunolocalization studies show that Kar3Cik1
      binds preferentially to one end of the microtubule, whereas the Kar3 motor
      domain, in the absence of Cik1, exhibits significantly higher microtubule lattice
      binding. Kar3Cik1-promoted microtubule depolymerization requires ATP turnover,
      and the kinetics fit a single exponential function. The disassembly mechanism is
      not microtubule catastrophe like that induced by the MCAK Kinesin-13s. Soluble
      tubulin does not activate the ATPase activity of Kar3Cik1, and there is no
      evidence of Kar3Cik1(.)tubulin complex formation as observed for MCAK. These
      results reveal a novel mechanism to regulate microtubule depolymerization. We
      propose that Cik1 targets Kar3 to the microtubule plus end. Kar3Cik1 then uses
      its minus-end-directed force to depolymerize microtubules from the plus end, with
      each tubulin-subunit release event tightly coupled to one ATP turnover.

PMID- 16085498
TI  - The PHD finger/bromodomain of NoRC interacts with acetylated histone H4K16 and is
      sufficient for rDNA silencing.
AB  - The SNF2h-containing chromatin-remodeling complex NoRC is responsible for
      silencing a fraction of mammalian rRNA genes (rDNA). NoRC silences transcription
      by establishing heterochromatic features-including DNA methylation,
      hypoacetylation of histone H4, and methylation of H3K9-at the rDNA promoter [].
      We have investigated the mechanism of NoRC-mediated rDNA silencing and show that
      binding of the bromodomain of TIP5, the large subunit of NoRC, to acetylated
      nucleosomes is a prerequisite for NoRC function. A point mutation within the
      bromodomain impairs the association of NoRC with chromatin, prevents
      heterochromatin formation, and abolishes transcriptional repression. Moreover,
      the association of NoRC with chromatin requires acetylation of histone H4 at
      lysine 16 (acH4K16), and binding to acH4K16 is required for subsequent
      deacetylation of H4K5, H4K8, and H4K12, indicating that acetylation of H4K16
      plays an active role in NoRC-mediated heterochromatin formation. The bromodomain
      cooperates with an adjacent PHD finger to recruit HDAC1, DNMT1, DNMT3, and SNF2h
      to rDNA. If specifically targeted to the rDNA promoter, the PHD
      finger/bromodomain is capable of establishing heterochromatic features and rDNA
      silencing. Thus, the PHD finger/bromodomain represents an autonomous unit that
      binds to acH4K16 and coordinates the chain of events that establish the repressed
      state of rDNA.

PMID- 16085500
TI  - Does nicotine do what we think it does? A meta-analytic review of the subjective
      effects of nicotine in nasal spray and intravenous studies with smokers and
      nonsmokers.
AB  - We conducted a meta-analysis of placebo-controlled laboratory studies of the
      subjective effects of nicotine. A total of 15 studies (11 with nasal spray, four
      with intravenous administration) with smokers and six studies (all with nasal
      spray) with never-smokers were included. Studies of other routes of
      administration (e.g., smoked tobacco) were not included because of insufficient
      numbers of available effect sizes. Meta-analysis results indicated that nicotine
      increased vigor for smokers but increased fatigue for never-smokers. Nicotine
      increased head rush for both smokers and never-smokers. In studies of smokers
      only, nicotine also increased ratings of drug high and drug liking. Contrary to
      expectations, nicotine decreased relaxation and increased tension/jitteriness for
      both smokers and never-smokers. Dose-response relationships were most clearly
      observed for head rush and drug high. Considerable variability was found across
      studies for a given nicotine dose and route of administration. Implications of
      the current findings about the role of subjective effects in nicotine
      reinforcement and self-administration are discussed along with commentary on
      methodological issues and recommendations for future studies.

PMID- 16085501
TI  - Adverse effects of pharmacological therapy for nicotine addiction in smokers
      following a smoking cessation program.
AB  - This multicenter, community-based, prospective, longitudinal study evaluated the
      safety of nicotine replacement therapy (NRT), bupropion, and combined therapy of
      NRT and bupropion for smokers seeking to quit, when these therapies were used
      under real-world conditions following a smoking cessation program. Participants
      were smokers aged 18 years or older who attended five smoking cessation clinics.
      Evaluations were made at 15, 30, 60, and 90 days. We investigated the possible
      existence of adverse effects as well as the severity of each adverse effect and
      its influence on the treatment course. The study included 904 smokers: 370
      received NRT, 413 received bupropion, and 121 received combined therapy. At 15,
      30, 60, and 90 days, adverse effects were reported by 43.8%, 33.1%, 22.3%, and
      5.7% of subjects, respectively. Adverse effects were significantly more frequent
      in subjects receiving combined therapy or bupropion alone than in NRT-treated
      subjects at the 15-, 30-, and 60-day follow-ups. A total of 83 smokers (9.3%)
      withdrew from treatment and 116 (12.8%) stopped temporarily because of adverse
      effects. No differences were found in the percentages of discontinuation among
      the different treatment options. Adverse effects rarely were severe (n=10).
      Nevertheless, 41 subjects (4.5%) discontinued drug therapy indefinitely and 55
      (6.1%) discontinued it temporarily because of mild adverse effects.
      Pharmacological therapies for smoking cessation are safe as long as they are
      appropriately prescribed and supervised by clinicians according to clinical
      practice guidelines. Adverse effects are primarily mild. Nonetheless, mild
      adverse effects may be perceived by patients as a serious enough problem to cause
      them to discontinue treatment.

PMID- 16085502
TI  - The nicotine market: an attempt to estimate the nicotine intake from various
      sources and the total nicotine consumption in some countries.
AB  - Tobacco--particularly smoked products--has been associated with great harm and
      growing public disapproval and can be expected to suffer in the marketplace. This
      situation has created opportunities for other less harmful nicotine-containing
      products such as smokeless tobacco and nicotine replacement products, which are
      gaining public support. Little is known about the level of nicotine intake in our
      society. Tobacco sales are known, but how much nicotine is extracted and actually
      absorbed by users is largely unknown. The present study is a first attempt to
      estimate uptake of nicotine from tobacco and nicotine replacement products and to
      map nicotine consumption in a few countries, with special emphasis on Sweden.
      Relevant pharmacokinetic studies for three types of nicotine-containing products
      (cigarettes, smokeless tobacco, and nicotine replacement products) were analyzed
      for bioavailable nicotine. Estimates of nicotine intake from each category were
      made. These were then multiplied by the amount consumed in the respective
      countries. Tobacco consumption statistics were usually from official records of
      taxed sales. In Sweden about 54% of all nicotine intake comes from smoked
      sources, 45% from nonsmoked tobacco, and 1.3% from nicotine replacement products.
      For men, 63% of the nicotine consumed comes from nonsmoked tobacco. Per-capita
      nicotine intake per year for adults aged 15 years or older is 3,321 mg for
      Austria, 3,043 mg for Sweden, 3,014 mg for Denmark, 2,955 mg for the United
      States, 2,244 mg for Norway, and 2,023 mg for Finland. Compared with cigarette
      smokers, snus users seem to have a somewhat higher daily intake (34 mg vs. 25
      mg). The cleanest nicotine products, nicotine replacement products, represent a
      negligible part (about 1%) of the total nicotine consumption in most countries.

PMID- 16085503
TI  - The types of regular cigarette smokers: a latent class analysis.
AB  - The present study sought to refine cigarette smoking exposure by examining
      whether individuals with a history of regular cigarette smoking could be
      classified into meaningful subgroups based on their smoking habits, nicotine
      dependence, and quit attempts. Data were obtained from 3,025 male and female
      twins aged 22-59 years who participated in two longitudinal studies based on the
      Virginia Twin Registry. Latent class analysis was used to identify the number and
      nature of subgroups of smokers reporting similar smoking habits based on 18
      characteristics. Estimates of prevalence for different classes of smoking were
      obtained along with expected frequencies of endorsements for each smoking
      behavior by class. Distributions of demographic characteristics, psychopathology,
      and personality were examined as external validators. The results demonstrated
      considerable heterogeneity and revealed eight classes of smokers who differed in
      their degree of nicotine dependence, cessation attempts, and ability to quit
      smoking. Smoking classes ranged from individuals who were all former smokers with
      low nicotine dependence who attempted to quit once and were successful, to
      individuals who were all current smokers with little desire to quit, to
      individuals with high nicotine dependence with multiple quit attempts, only a
      subset of which were successful. Estimates of prevalence for each class were 9%
      20%. Our findings support the idea that regular cigarette smokers are highly
      heterogeneous and highlight the need for smoking exposure refinement in future
      studies. Acknowledging the complexity of cigarette smoking and classifying
      smokers into more specific subgroups based on their smoking behavior in future
      studies will enable more accurate evaluation of disease etiology and risk and
      could lead to more appropriate smoking cessation interventions.

PMID- 16085504
TI  - Dopamine receptor (DRD2) genotype-dependent effects of nicotine on attention and
      distraction during rapid visual information processing.
AB  - The effects of nicotine, distractor type, and dopamine type-2 receptor (DRD2)
      genotype on rapid visual information processing (RVIP) task performance were
      assessed in habitual smokers. Four RVIP tasks differed in terms of distractor
      location (central vs. peripheral) and distractor type (numeric vs. emotional).
      Each participant performed each of the tasks on two different days, once while
      wearing an active nicotine patch and once while wearing a placebo patch. Overall,
      the nicotine patch produced more accurate detection of and faster reaction times
      to target sequences; however, these effects varied with distractor type and
      genotype. Nicotine speeded reaction time more with left-visual-field (LVF) than
      right-visual-field (RVF) emotional distractors but speeded reaction time more
      with RVF than LVF numeric distractors, especially when the distractor digit
      matched the target sequence in terms of numeric oddness or evenness. Nicotine
      tended to facilitate performance more in individuals with at least one A1 allele
      than in homozygous A2A2 individuals, especially with numeric distractors
      presented to the left hemisphere. Nicotine tended to reduce distraction by
      negative stimuli more than other types of stimuli. Few gender differences were
      observed. The overall pattern of results was consistent with the view that
      nicotine modulates selective attention or subsequent information processing in a
      manner that depends partly on the emotional versus numeric nature of task
      distractors, DRD2 genotype, and the brain hemisphere that initially processes the
      distractors (visual field of distractor).

PMID- 16085505
TI  - Television viewing and age at smoking initiation: does a relationship exist
      between higher levels of television viewing and earlier onset of smoking?
AB  - This cross-sectional study of children assessed the association between
      television viewing and age at smoking initiation, using self-reports administered
      by research assistants in schools. Participants were 909 students in their first
      and fourth years of secondary education in a random sample of 15 secondary
      schools in Flanders, Belgium, who had smoked at least one cigarette. The main
      outcome measure was age at smoking initiation. The independent variable was
      weekly television viewing volume. Gender, educational level, parental smoking,
      and peer smoking were the control variables. The relationship between television
      viewing and age at smoking initiation was significant. Higher levels of
      television viewing were related to earlier onset of smoking behavior in
      adolescents. The relationship of television viewing with age at smoking
      initiation was stronger than that of peer smoking, parental smoking, and gender.
      For each hour of television viewing per day, the average smoking initiation age
      decreased by 60 days. Heavier television viewers start smoking at an earlier age.
      Two possible explanations for this relationship are suggested. Social learning
      theory suggests that actors and actresses serve as behavioral role models for
      heavy viewers. Cultivation theory suggests that exposure to positive messages
      influences smoking attitudes. Further research should examine whether the
      relationship is causal and whether television acts as a provider of smoking role
      models or whether it influences smoking attitudes.

PMID- 16085506
TI  - The relationship of smoking cessation to sociodemographic characteristics,
      smoking intensity, and tobacco control policies.
AB  - The present study examined the relationship between recent smoking cessation
      activities and sociodemographic characteristics, smoking intensity, and tobacco
      control policies among daily smokers in the United States. The study used the
      U.S. Current Population Survey 1998-1999 Tobacco Use Supplement, supplemented
      with information on state-level tobacco control policies. The sample was limited
      to individuals aged 25 years or older who were smoking daily 1 year ago. We
      estimated frequencies and multivariate logistic equations for making a quit
      attempt and remaining abstinent at least 3 months. These measures were related to
      demographic characteristics, smoking intensity, and tobacco control policies.
      Younger, higher socioeconomic status (SES), and less intense (fewer cigarettes
      per day) daily smokers were more likely to make quit attempts, but the likelihood
      of remaining abstinent for those making a quit attempt was greater for older,
      higher SES, and heavy daily smokers. We found evidence that cessation behaviors
      were related to higher cigarette prices and the presence of state-level
      media/comprehensive campaigns, but less clear evidence exists for an association
      with bans restricting workplace smoking. The results indicate that certain types
      of smokers are more likely to attempt to quit and to have success and that the
      characteristics of these smokers differ. Price policies can have an important
      role in helping daily smokers to quit. Further research is needed regarding the
      role of quantity smoked.

PMID- 16085507
TI  - Steady-state nicotine plasma levels following use of four different types of
      Swedish snus compared with 2-mg Nicorette chewing gum: a crossover study.
AB  - The present study evaluated nicotine plasma levels achieved following 1 day's
      regular use of four commonly used brands of Swedish portion snus and 2-mg
      Nicorette chewing gum. The study also estimated the amount of sodium chloride
      extracted from each snus sachet to identify potential risks for exacerbation of
      heart failure and hypertension with the use of Swedish snus. Extracted dose of
      nicotine, area under the venous plasma concentration-time curve (AUC), maximum
      plasma nicotine concentration (Cmax) of the last (12th) dosing interval, and the
      Cmax and AUC ratios versus Nicorette were calculated. Relative bioavailable dose
      was calculated using AUC of 2-mg Nicorette gum as the reference. The mean
      extracted nicotine doses were 2.74+/-0.80, 1.55+/-0.68, 2.00+/-0.56, and 1.08+/
      0.94 mg/sachet for General, Catch Licorice, Catch Mini, and Catch Dry Mini snus,
      respectively. The approximate bioavailable dose of nicotine from snus was 40%-60%
      of the extracted dose. The steady-state nicotine plasma concentration-time curve
      for the weakest brand, Catch Dry Mini portion snus, did not differ significantly
      from that of the 2-mg Nicorette gum. The AUC and Cmax for Catch Licorice 1 g and
      Catch Mini 0.5 g portion snus were twice those for the 2-mg Nicorette gum; for
      the strongest brand, General, these values were 2(1/2) times those for Nicorette
      gum. The differences in AUC and Cmax versus the 2-mg Nicorette gum were
      statistically significant (p=.020). Nicotine plasma levels with General portion
      snus were sustained at higher levels than current nicotine replacement therapy
      products, peaking at 29.0+/-8.5 ng/ml, and more closely mimicking cigarette
      smokers' nicotine plasma levels. The risks of aggravation of heart failure and
      hypertension with respect to increased salt load from the use of snus appeared to
      be negligible.

PMID- 16085508
TI  - Recruitment of physician offices for an office-based adolescent smoking cessation
      study.
AB  - Physician office settings play an important role in tobacco cessation
      intervention. However, few tobacco cessation trials are conducted at these sites,
      in part because of the many challenges associated with recruiting community
      physician offices into research. The present study identified and implemented
      strategies for recruiting physician offices into a randomized clinical trial of
      tobacco screening and cessation interventions with adolescent patients. A total
      of 30 community physicians participated in focus groups to elicit their
      perceptions of facilitators of and barriers to initial engagement of physician
      practices and the subsequent enrollment of the practices in long-term research
      projects. Physicians identified facilitators such as (a) the involvement of
      office staff in the recruitment process and (b) on-site presentations of the
      study's background and aims. Some of the barriers identified were time commitment
      concerns and the lack of incentives in exchange for participation. These focus
      group findings were then integrated with theory-based and empirically driven
      recruitment strategies for a 12-month randomized tobacco intervention trial with
      adolescent patients. Of 185 office practices approached to participate (screened
      from a pool of 273 practices), 103 agreed to on-site presentations of the study.
      Subsequently, almost all of the practices (101) that received the presentation
      agreed to enroll in the study. Conclusions are that (a) recruitment is a
      multicomponent process, (b) the processes of communication, engagement, and
      enrollment must be carefully planned and implemented to achieve maximal results,
      and (c) the development of effective strategies for recruiting health care
      provider practices presents an important infrastructure for testing adolescent
      smoking cessation interventions.

PMID- 16085509
TI  - A twin-sibling study of tobacco use in adolescence: etiology of individual
      differences and extreme scores.
AB  - A database is emerging that examines the relative contributions of genes and the
      environment to the etiology of smoking in adolescence. We present analyses
      derived from a genetically informative subsample of sibling pairs (monozygotic
      and dizygotic twins, full siblings, and half-siblings) participating in two waves
      of the National Longitudinal Study of Adolescent Health to estimate these
      parameters on both individual differences in smoking and extreme levels of
      smoking. Evidence indicated both genetic and shared environmental influences on
      high levels of smoking frequency, as well as on individual differences in
      smoking. No notable gender differences in these parameters emerged. Shared
      environmental effects were especially notable for high levels of smoking
      frequency and significantly greater than those found for individual differences.
      These findings were compatible with prior studies of both adolescent and adult
      smoking and reinforce the importance of familial influences on high levels of
      smoking frequency in adolescence.

PMID- 16085510
TI  - Subjective and physiological responses to smoking cues in smokers with
      schizophrenia.
AB  - The prevalence of smoking is high among people with schizophrenia. Although
      several research groups are developing smoking treatments for these smokers,
      abstinence rates to date have been modest. Methodological tools such as cue
      exposure are useful in clinical research with smokers in general, but the value
      of these paradigms with smokers with schizophrenia has yet to be established. The
      aim of the present study was to determine the subjective and physiological
      effects of exposure to in vivo smoking cues in smokers with schizophrenia. A
      total of 25 heavy smokers with schizophrenia or schizoaffective disorder were
      assessed while nonabstinent and after 2-hr smoking abstinence. Urge to smoke,
      mood, nicotine withdrawal symptoms, heart rate, and blood pressure were measured
      during a precue relaxation period, after exposure to neutral cues, and after
      exposure to smoking cues. Results indicate that both exposure to smoking cues and
      brief abstinence increased urge levels, nicotine withdrawal symptom levels, and
      negative affect. Abstinence did not amplify the effects of cues on urges or other
      cue reactivity measures. These results indicate that smoking cue reactivity
      laboratory models may be useful for investigating potential smoking treatments
      for, or neurobiological contributions to, smoking behavior in smokers with
      schizophrenia.

PMID- 16085511
TI  - Prevalence and correlates of lifetime smokeless tobacco use in female military
      recruits.
AB  - Although considerable research has been conducted on smokeless tobacco (ST) use
      in males, much less is known about the characteristics of female ST users. The
      present study examined the prevalence and correlates of lifetime ST use among
      female Air Force recruits (N=9,087). Participants were surveyed during Basic
      Military Training regarding their history of tobacco use and other health risk
      behaviors. Although the prevalence of current ST use was low (<1%; n=34), 6.6%
      (n=599) had tried ST. Multivariate logistic regression analysis indicated that
      lifetime ST use was related to ethnicity, with Native Americans and Whites being
      most likely to have tried ST. Additional correlates of lifetime ST use included
      post-high-school education (OR=1.26, 95% CI=1.03-1.55); weekly acts of road rage
      (OR=1.48, 95% CI=1.06-2.06); frequent arguing (OR=1.71, 95% CI=1.18-2.48); daily
      or near-daily alcohol consumption (OR=1.71, 95% CI=1.03-2.82); current cigarette
      use (OR=3.80, 95% CI=2.42-5.94); and experimental use of cigars (OR=4.01, 95%
      CI=3.22-5.01), pipes (OR=2.23, 95% CI=1.64-3.03), and clove cigarettes (OR=1.23,
      95% CI=1.01-1.49), all of which were associated with an increased likelihood of
      ST use. Results suggest that female recruits who have ever used ST engage in a
      variety of risk behaviors including use of other tobacco products and alcohol, as
      well as additional harmful behaviors.

PMID- 16085512
TI  - Determination of carcinogenic tobacco-specific nitrosamines in mainstream smoke
      from U.S.-brand and non-U.S.-brand cigarettes from 14 countries.
AB  - Tobacco-specific nitrosamines (TSNAs) comprise one of the major classes of
      carcinogenic compounds in mainstream cigarette smoke. As part of collaborative
      efforts between the World Health Organization and the U.S. Centers for Disease
      Control and Prevention (CDC) to reduce tobacco use and resulting disease, the CDC
      examined carcinogenic TSNA levels from cigarettes obtained from selected
      countries around the world. Using a modern, high-throughput liquid
      chromatography/mass spectrometry/mass spectrometry method under stringent quality
      control protocols, we determined the carcinogenic TSNA levels in mainstream smoke
      from a globally marketed brand, Marlboro, and from local top-selling cigarette
      brands from 14 countries. The levels of carcinogenic TSNAs in mainstream smoke
      collected using a 35-ml puff volume, 60-s puff interval, and 2-s puff duration
      correlated well (R=0.79, p<.0001) with previously reported levels in the
      corresponding tobacco filler. Marlboro cigarettes purchased in 10 countries had
      significantly higher carcinogenic TSNA levels in mainstream smoke than did local
      brand cigarettes from the same country. In only one country, Brazil, were the
      carcinogenic TSNA levels in mainstream smoke from Marlboro cigarettes
      significantly lower than in the locally popular brand. However, carcinogenic TSNA
      levels in mainstream smoke from Brazilian Marlboro cigarettes were usually lower
      than those in mainstream smoke from the Marlboros purchased in the other 13
      countries, suggesting a reason for the difference. The wide range of mainstream
      smoke carcinogenic TSNA levels measured in the present study (8.7-312
      ng/cigarette) suggest that manufacturers can lower the carcinogenic TSNA levels
      and that, for similar filter ventilation, carcinogenic TSNA levels in the tobacco
      filler of a cigarette are a useful indicator of the corresponding levels in
      mainstream smoke.

PMID- 16085513
TI  - Preliminary evidence of the association between the history of childhood
      attention-deficit/hyperactivity disorder and smoking treatment failure.
AB  - Smoking rates are elevated among individuals with attention-deficit/hyperactivity
      disorder (ADHD). The association of ADHD diagnosis and smoking treatment outcome
      has not been examined. The present study examined abstinence rates among 428
      adult smokers participating in two randomized controlled trials. Treatments
      included nicotine replacement, antidepressants, and psychological interventions.
      Childhood ADHD was assessed retrospectively by diagnostic interview. In a
      survival analysis, ADHD status predicted time to relapse after controlling for
      gender, history of depression, and baseline smoking variables. Only 1 of 47
      participants with a history of childhood ADHD remained abstinent by week 52,
      compared with 18% of those who had no history of childhood ADHD (adjusted
      OR=0.36, 95% CI=0.28-0.45). The current findings provide preliminary evidence for
      an association between childhood ADHD and smoking cessation treatment failure.
      Further investigation is warranted.

PMID- 16085514
TI  - Characteristics of low-level smokers.
AB  - Average daily cigarette consumption has decreased, and some evidence suggests
      that the rate of "some day" smoking has increased; however, relatively little is
      known about low-level smokers. The present analysis describes and compares low
      level versus heavier smokers, using cross-sectional and longitudinal data. Data
      from the Community Intervention Trial for Smoking Cessation (COMMIT) were used in
      this analysis. Population-based cross-sectional tobacco use telephone surveys
      were performed in 22 North American communities in 1988 and 1993, and the
      prevalence and characteristics of low-level smoking and reasons for quitting are
      reported from the 1993 prevalence survey. In addition, a cohort of 6,603 smokers
      was identified in 1988 and interviewed again in 1993 and 2001 to assess patterns
      of low-level smoking over time and its association with smoking cessation. In
      1988, 7.6% were low-level smokers; in 1993, 10.7% were low-level smokers.
      Compared with heavier smokers, low-level smokers were more likely to be female,
      older, not married, Black or Hispanic; to have a 4-year college degree; to have
      no other adult smokers in the household; and to wait longer in the day to have
      their first cigarette. Low-level smokers also were less likely to report trying
      to quit because of the expense of smoking or physician advice to quit. They were
      more likely to try to quit because of trying to set a good example; concern for
      second-hand smoke; and factors such as bad breath, smell, or the taste of
      smoking. Those who smoked full-priced premium brands and who worked in a
      completely smoke-free worksite were more likely to be low-level smokers. Compared
      with heavier smokers, low-level smokers had similar rates of making a future quit
      attempt, lower use rates of nicotine replacement therapy, and higher cessation
      rates. Low-level smokers may be a growing segment of the smoker population and
      have different characteristics, health risks, and intervention needs compared
      with their heavier smoking counterparts.

PMID- 16085515
TI  - Smokeless tobacco topography and toxin exposure.
AB  - This study examined the relationship between oral smokeless tobacco (ST)
      topographical measures and biomarkers of tobacco and carcinogen exposure. During
      2 weeks of baseline ad libitum ST use, 54 male participants (mean age=32.1+/-7.5
      years) were required to record the time each dip was placed in and removed from
      their mouths. Urine samples were collected twice during baseline and analyzed for
      nicotine, cotinine, and their glucuronides (total nicotine and total cotinine)
      and for metabolites of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its
      glucuronides (total NNAL). The results suggest that frequency and duration
      measures of ST use (p<.01 to p<.001), particularly total dip duration, are
      significantly correlated with total cotinine, total nicotine, and total NNAL.
      These results suggest that how long a ST user has tobacco in his mouth is most
      predictive of tobacco toxin exposure.

PMID- 16085516
TI  - Smoking policies in U.S. outpatient drug treatment facilities.
AB  - Most drug treatment patients smoke cigarettes, and some facilities are beginning
      to help patients quit. Facility smoking policies can help or hinder this effort.
      The present study describes smoking policies in outpatient drug treatment. It is
      a secondary analysis of a survey on smoking cessation treatment in outpatient
      methadone maintenance facilities in the United States. One clinic leader (a
      medical director, head nurse, or clinic director) from each of the 697 U.S.
      facilities was invited to participate in the study. Main outcome measures
      included whether clinics had a written smoking policy as well as the types of
      indoor and outdoor policies in place for patients and staff. A total of 408 (59%)
      of U.S. clinics responded. Most clinics (73%) had a written smoking policy for
      patients, and more (82%) had written policies for staff. Over 90% banned indoor
      smoking by staff and patients. Few totally banned outdoor smoking. Approximately
      half in some way restricted where patients (48%) and staff (55%) smoke outdoors.
      Compared with clinics that did not treat nicotine dependence, significantly more
      clinics that treated nicotine dependence had written policies on smoking and
      restricted outdoor smoking for patients and staff. Likewise, many public clinics
      and those affiliated with hospitals had outdoor smoking restrictions for patients
      and staff. Drug treatment facilities routinely ban alcohol use and drug dealing
      on their grounds. Only 1 in 10 ban smoking. Outpatient facilities should restrict
      or ban outdoor tobacco use in order to remain consistent with their mission and
      avoid sabotaging clinic efforts to treat, and patient and staff efforts to stop,
      smoking.

PMID- 16085517
TI  - Formal learning theory and nicotine dependence: response to Balfour.

PMID- 16085520
TI  - Nortriptyline for smoking cessation: a review.
AB  - This article reviews the efficacy of nortriptyline for smoking cessation based on
      a meta-analysis of the Cochrane Library. Six placebo-controlled trials have shown
      nortriptyline (75-100 mg) doubles quit rates (OR = 2.1). Between 4% and 12% of
      smokers dropped out because of adverse events, but no serious adverse events
      occurred. The efficacy of nortriptyline did not appear to be related to its
      antidepressant actions. Nortriptyline is an efficacious aid to smoking cessation
      with a magnitude of effect similar to that for bupropion and nicotine replacement
      therapies. Whether nortriptyline produces serious side effects at these doses in
      healthy, nondepressed smokers remains unclear because it has been tested in only
      500 smokers. The finding that nortriptyline and bupropion are effective for
      smoking cessation but that selective serotonin-reuptake inhibitors are not
      suggests that dopaminergic or adrenergic, but not serotonergic, activity is
      important for cessation efficacy. Until further studies can verify a low
      incidence of significant adverse events, nortriptyline should be a second-line
      treatment for smoking cessation.

PMID- 16085521
TI  - Parental smoking cessation and children's smoking: mediation by antismoking
      actions.
AB  - The present study investigated whether parents' antismoking actions mediated the
      prospective relationship between parental smoking cessation and children's
      smoking. Smoking status of parents (predictor) was assessed when their children
      were in 3rd grade, parental antismoking actions (mediators) were assessed when
      their children were in 11th grade, and children's smoking status (outcome) was
      assessed when they were in 12th grade. In 20 Washington state school districts,
      data were collected from 1,600 children (49% female, 91% White) and from their
      parents. Results showed that children's odds of daily smoking were reduced by 39%
      (95% CI = 24%-51%) for those whose parents had quit smoking, compared with those
      whose parents were current smokers. Asking to sit in nonsmoking sections of
      public establishments was a significant (p<.01) mediator that explained 64% of
      the association between parental smoking cessation and children's smoking.
      However, not allowing smoking in the home and asking others not to smoke around
      them were not significant mediators (p = .10, and p = .06, respectively). In
      conclusion, asking to sit in a nonsmoking section of a public establishment
      substantially mediates the relationship between parental smoking cessation and
      children's smoking.

PMID- 16085522
TI  - Tobacco use and readiness to quit smoking in low-income HIV-infected persons.
AB  - The study aim was to identify covariates of smoking status and readiness to quit
      that encompassed key sociodemographic and health status variables, health-related
      quality of life, drug use and unprotected sex, and tobacco use variables in a
      cohort of low-income persons living with HIV. We also examined the impact of HIV
      diagnosis on smoking cessation. The sample (N = 428) was mostly male (59%) and
      Black (53%) or Hispanic (30%), and had a high school education or less (87%).
      Mean age was 40 years. Two-thirds of participants were current smokers, 19%
      former smokers, and 16% never smokers. Current smokers smoked a mean of 16
      cigarettes/day for 22 years; 42% were in the precontemplation stage of readiness
      to quit smoking, 40% were contemplators, and 18% were in preparation. Most
      current smokers (81%) reported receiving medical advice to quit smoking.
      Multivariate logistic regression analyses indicated that current smokers,
      compared with former smokers, were more likely to use illicit drugs, perceive a
      lower health risk for continued smoking, and report less pain. Current smokers,
      compared with nonsmokers (former and never smokers), were more likely to report
      greater illicit drug use in their lifetime, current illicit drug use, and less
      pain. A multiple linear regression indicated that greater current illicit drug
      use, greater emotional distress, and a lower number of quit attempts were
      associated with lower stage of readiness to quit smoking. These findings confirm
      a high prevalence of smoking among HIV-infected persons and suggest a complex
      interplay among drug use, pain, and emotional distress that impact smoking status
      and, among smokers, readiness to quit. Tobacco control programs for HIV-infected
      persons should build motivation to quit smoking and address salient barriers to
      cessation--such as comorbid drug use, emotional distress, pain, and access to and
      coverage for treatment--and should educate smokers regarding the HIV-specific
      health benefits of cessation.

PMID- 16085523
TI  - Characterization of measured menthol in 48 U.S. cigarette sub-brands.
AB  - More than 25% of cigarettes sold in the United States are branded as mentholated,
      and these cigarettes are smoked disproportionately among populations with
      disparate tobacco-related health outcomes. This study is the first (independent
      of the tobacco industry) to report menthol for 48 popular commercially available
      mentholated cigarette sub-brands. The dependent variable "menthol per cigarette"
      was obtained by gas chromatography-mass spectrometer assay, whereas average per
      cigarette milligram weight of tobacco filler ("tobacco per cigarette") was
      determined gravimetrically. Pearson's correlations assessed associations among
      continuous variables. Analyses of variance assessed mean differences on the
      independent variables of interest: manufacturer, brand family, industry
      descriptors of length (100 mm and King [85 mm]) and label (ultralight, light,
      medium/mild, and regular/full flavor), and a category constructed by the authors
      of exclusively menthol brand families (those without a non-menthol offering;
      Kool, Newport, and Salem) versus others (GPC, Camel, and Marlboro). Results
      showed menthol per cigarette and menthol per tobacco (i.e., milligrams of menthol
      per gram of tobacco filler) to be significantly greater in cigarettes labeled
      with industry descriptors of ultralight or light, belying the common consumer
      perception that "light" means less. Menthol per cigarette and tobacco per
      cigarette were significantly greater in 100-mm compared with 85-mm cigarettes.
      The study results are consistent with prior research that suggests menthol may be
      used to offset reductions in smoke delivery or impact and to facilitate
      compensatory smoke inhalation behaviors in smokers of cigarettes with reduced
      machine-measured smoke delivery. Tobacco manufacturers should be required by
      federal or other regulatory agencies to report the amount of menthol added to
      cigarettes.

PMID- 16085524
TI  - The return to smoking: 1-year relapse trajectories among female smokers.
AB  - Research has demonstrated that a lapse in cigarette abstinence often leads
      smokers to fully relapse (i.e., return to daily smoking). However, patterns of
      smoking resumption beyond the point at which relapse occurs have not been
      examined in systematic follow-up studies. Daily cigarette intake data for 108
      female adult smokers who participated in a smoking cessation trial were recorded
      at several points during the 365 days following the participants' quit date. SAS
      Proc Traj, a group-based mixture modeling procedure, was used to determine
      cigarette-use trajectories over time (i.e., patterns of smoking resumption). Over
      the 365 days, 27% of the sample maintained abstinence. Among the 73% who
      relapsed, four distinct trajectories emerged: low-level users (8% of the overall
      sample), moderate users (17%), slow-returners (15%), and quick-returners (33%). A
      few individual characteristics differentiated these groups. Overall, the findings
      illustrate that, after relapsing, smokers do not follow a unitary course of
      smoking resumption; rather, they exhibit more variable resumption patterns than
      previously assumed.

PMID- 16085525
TI  - U.K. general practitioners' beliefs, attitudes, and reported prescribing of
      nicotine replacement therapy in pregnancy.
AB  - Clinical guidelines recommend that U.K. health professionals prescribe NRT in
      pregnancy. The present study was conducted to determine (a) general
      practitioners' confidence in their ability to deliver a range of smoking
      cessation interventions, including NRT, in pregnancy, (b) the frequency with
      which general practitioners recall prescribing NRT in pregnancy, and (c) the
      factors that influence general practitioners to prescribe NRT in pregnancy. We
      conducted a mail survey of 368 general practitioners (family physicians) working
      in four districts of Nottingham, England (response rate = 68.6%). Some 27.1% of
      respondents recalled prescribing NRT to pregnant women (9.2% were unsure).
      General practitioners were less confident about their ability to prescribe NRT in
      pregnancy than they were of their ability to deliver other simple smoking
      cessation interventions in pregnancy. Most general practitioners (62%) believed
      NRT to be effective in pregnancy and safer than smoking (70%), but fewer (45%)
      believed NRT to be safe in pregnancy per se. Multiple logistic regression
      demonstrated that general practitioners who believed NRT use in pregnancy was
      safer than smoking were most likely to recall having prescribed it, OR = 4.94,
      95% CI = 1.31-18.71. Many general practitioners were unsure about the safety of
      NRT in pregnancy, which may explain their relatively low confidence in their
      ability to prescribe NRT in pregnancy, compared with other interventions. The key
      factor influencing general practitioners' prescribing decisions was a belief that
      NRT use in pregnancy was likely to be safer than smoking. Empirical evidence
      about the safety and efficacy of NRT use in pregnancy is required to inform
      general practitioners' decisions about prescribing NRT to pregnant women who
      smoke.

PMID- 16085526
TI  - Over-the-counter availability of nicotine replacement therapy and smoking
      cessation.
AB  - In 1996, the FDA approved over-the-counter (OTC) availability of nicotine gum and
      two brands of nicotine skin patches. Little is known about how this
      reclassification has influenced the effectiveness and use of nicotine replacement
      therapy (NRT) and whether it has been a public health benefit. Data for the
      present study came from a prospective cohort study of 1,639 adult smokers
      surveyed by telephone in 1993, as part of the National Cancer Institute's
      Community Intervention Trial for Smoking Cessation (COMMIT), and resurveyed in
      2001. NRT-assisted quit rates, NRT use rates, and the characteristics of NRT
      users were calculated before and after the 1996 OTC reclassification. Also
      calculated was the percentage of NRT users who quit by year. Results are
      presented for patch and gum separately and combined. OTC NRT use rates were lower
      for Hispanics and higher for those with no desire to quit at baseline. The quit
      rate decreased for patch-assisted quit attempts after OTC reclassification (22.5%
      to 18.5%, p = .05), but it did not change for gum-assisted quit attempts (11.9%
      to 10.5%, p = .54). NRT use rates increased for both patch and gum by about 60%
      following reclassification. A greater percentage of gum users had quit in the
      post-OTC period than in the pre-OTC period (9.7% vs. 14.6%, p = .05). Long-term
      quit rates in patch users were similar in both periods. Insurance coverage of NRT
      and concurrent attendance in a stop smoking clinic decreased for both patch- and
      gum-assisted attempts in the post-OTC period. The results suggest that OTC
      reclassification may have contributed to the increased use of NRT, compared with
      the pre-OTC period, whereas the efficacy for quitting decreased slightly for
      those using nicotine patch and remained about the same for those using the gum.

PMID- 16085527
TI  - Active and passive smoking and blood lead levels in U.S. adults: data from the
      Third National Health and Nutrition Examination Survey.
AB  - Lead is a component of tobacco and tobacco smoke. We examined the relationship
      between current, former, and passive smoking and blood lead levels in a
      nationally representative sample of 16,458 U.S. adults, aged 17 years or older,
      who participated in the Third National Health and Nutrition Examination Survey
      (1988-1994). We used linear and logistic regression modeling, adjusting for known
      covariates, to determine the relationship between smoking and blood lead levels.
      Geometric mean blood lead levels were 1.8 microg/dl, 2.1 microg/dl, and 2.3
      microg/dl in never-smokers with no, low, and high cotinine levels, respectively.
      Levels were 2.9 microg/dl in former smokers and 3.5 microg/dl in current smokers.
      The adjusted linear regression model showed that geometric mean blood lead levels
      were 30% higher (95% CI = 24%-36%) in adults with high cotinine levels than they
      were in those with no detectable cotinine. Active and passive smoking is
      associated with increased blood lead levels in U.S. adults.

PMID- 16085528
TI  - Interventions to increase use of nicotine gum: a randomized, controlled, single
      blind trial.
AB  - Medication noncompliance with smoking cessation pharmacotherapies is a
      significant problem in both research and clinical settings. This randomized,
      controlled, single-blind study compared three single-session psychological
      interventions to increase use of nicotine gum during a 15-day treatment period. A
      total of 97 adult smokers were randomized to receive standard treatment (ST, n =
      31), brief feedback (BF, n = 32) plus ST, or contingency management (CM; i.e.,
      payment for chewing at least 12 pieces/day on 10 of 15 intervention days, n = 34)
      plus ST and BF. Only the CM condition led to significantly greater average daily
      gum use (pieces/day: ST, 6.17; BF, 7.81; CM, 10.17 [p values <.05]) and higher
      rates of compliance (ST, 13.6%; BF, 25.2%; CM, 65.6% [p values <.001]). No
      differences were observed in smoking abstinence, nicotine withdrawal, or urinary
      cotinine as a function of treatment. Implications of the present findings are
      discussed, including application to clinical trials and extension to real-world
      use of nicotine gum.

PMID- 16085529
TI  - The influence of gender, race, and menthol content on tobacco exposure measures.
AB  - Research has suggested that race, gender, and menthol cigarette use influence
      tobacco-smoke exposure measures and smoking-related disease risk. For example, a
      high proportion of Black smokers prefer menthol cigarettes and, despite smoking
      fewer cigarettes per day (CPD) than do Whites, tend to have higher cotinine
      levels. Additionally, Black males are more at risk for smoking-related lung
      cancer. High cotinine levels and smoking menthol cigarettes may lead to higher
      toxin intake, which contributes to increased disease risk. We explored the
      relationship between tobacco exposure variables (i.e., cotinine, CPD, carbon
      monoxide [CO], nicotine content, and nicotine dependence) with respect to race,
      gender, and menthol content in a sample of 307 smokers recruited from the greater
      Boston area to participate in a smoking cessation treatment trial. The pattern of
      correlations between tobacco exposure measures and cotinine showed a consistently
      positive correlation between cotinine and CO in all smokers and a correlation
      between cotinine and CPD in those who smoked nonmenthol cigarettes. Cotinine and
      CPD correlations varied by gender and race among menthol cigarette smokers.
      Consistently, we found a significant gender x race x menthol interaction on
      salivary cotinine level as well as cotinine/CPD ratio. These findings suggest
      that the relationship between number of cigarettes consumed and salivary cotinine
      is more complex than previously believed. It is not sufficient to look at race
      alone; researchers and clinicians need to look at race and gender concurrently,
      as well as type of cigarette consumed.

PMID- 16085530
TI  - Scientific analysis of second-hand smoke by the tobacco industry, 1929-1972.
AB  - The 1972 U.S. surgeon general's report The Health Consequences of Smoking was the
      first to include a warning about exposure to second-hand smoke. Because the
      tobacco industry has a record of withholding the results of their research from
      the public, we searched the internal tobacco industry documents and compared
      internal industry research on second-hand smoke to what the industry published in
      the open scientific literature through 1972. We found chemical analyses, sensory
      evaluations, and discussions of sidestream cigarette smoke (the smoke emitted by
      the cigarette between puffs, the main component of second-hand smoke), beginning
      in 1929. American Tobacco Company research in the 1930s indicated that, compared
      with mainstream smoke, sidestream smoke was produced in larger quantities and
      contained, per cigarette, 2 times more nicotine and 12 times more ammonia.
      Research funded by the Tobacco Industry Research Committee in the 1950s revealed
      that sidestream smoke contained, per unit cigarette, higher concentrations of
      carcinogenic polycyclic aromatic hydrocarbons, per unit mass, including four
      times more 3,4 benzopyrene. In 1956 and 1957, respectively, Philip Morris and R.
      J. Reynolds also began to research sidestream smoke. In 1961, Philip Morris began
      to do sensory evaluation and modification of sidestream odor during product
      development. This sensory evaluation of sidestream smoke was the first biological
      testing of sidestream smoke by a tobacco company. Prior to the release of the
      1972 U.S. surgeon general's report, the tobacco industry published the majority
      of its findings in the open scientific literature and does not appear to have
      perceived second-hand smoke as a threat to human health.

PMID- 16085531
TI  - Adolescents' smoking expectancies: psychometric properties and prediction of
      behavior change.
AB  - Outcome expectancies have been related to smoking behavior among adults, but less
      attention has been given to expectancies about smoking among adolescents at
      differing levels of smoking experience. The present study reports the
      psychometric properties and predictive validity of a brief expectancy scale
      across two samples of adolescents. Sample 1 (N = 349) consisted of high school
      students (54% female) who were regular smokers enrolled in a cessation program.
      Sample 2 (N = 273) consisted of 8th- and 10th-grade early experimenters (54%
      female) involved in a natural history study of smoking trajectories. In both
      samples, a principal component analysis of a 13-item expectancy scale yielded
      four factors (taste, weight control, boredom relief, and negative affect
      management), each with high internal consistency (coefficient alphas >.77) and
      accounting for 73% and 80% of the total variance for each sample, respectively.
      Expectancies were significantly higher among current smokers than among early
      initiators. In Sample 1, boredom relief and weight management expectancies
      predicted smoking status 6 months later. In Sample 2, students whose smoking
      increased over 18 months had higher overall expectancies at baseline compared
      with those who tried smoking and did not escalate. These findings support the
      predictive validity of expectancies in predicting escalation and cessation.
      Implications for the importance of expectancies in understanding adolescent
      smoking behavior are considered.

PMID- 16085532
TI  - How do smokers control their cigarette expenditures?
AB  - When faced with high cigarette prices, smokers can potentially control cigarette
      expenditures by limiting consumption or seeking cheaper cigarettes. The present
      study examined both these options and whether the use of price-minimizing
      strategies (the second option) could counteract a further price increase without
      smokers having to reduce consumption. Data for 5,109 smokers who purchased
      manufactured cigarettes were from the 2002 cross-sectional, population-based,
      random-digit-dialed California Tobacco Survey. We used logistic regression to
      examine which smokers used consumption-limiting or price-minimizing strategies,
      and multiple linear regression to determine how much price-minimizing strategies
      reduced the average price paid per pack. Overall, 32.3% of California smokers
      said they limited consumption and 74.1% used at least one of the five price
      minimizing strategies identified: choosing cheaper retail outlets (61.1%), using
      promotional offers (35.2%), choosing cheaper brands (28.7%), purchasing by the
      carton (27.7%), and using low-tax or nontaxed sources (6.3%). Different groups of
      smokers used different strategies. Except for the use of promotional offers, all
      price-minimizing strategies significantly reduced the price paid per pack. Carton
      purchasers saved 1.01 US dollars/pack, and those buying from low-tax or nontaxed
      sources saved 1.23 US dollars/pack. However, pack buyers were reluctant to
      purchase cartons, mostly because they thought they might smoke too much, or
      because they considered the upfront cost unaffordable. The average California
      smoker could potentially save 0.33-0.66 US dollars/pack or 6.00-12.00 US
      dollars/month by using other price-minimizing strategies. Reducing consumption by
      3 cigarettes/day could save a smoker 18.00 US dollars/month. Whereas price
      minimizing strategies appeared to save money, cutting consumption could save even
      more. Thus further substantial tax increases would likely have the desired
      effect.

PMID- 16085534
TI  - Abstracts of the 6th European Conference of SRNT Europe, Tubingen, Germany, 6-9
      October 2004.

PMID- 16085537
TI  - The antiphospholipid syndrome.
AB  - Antiphospholipid syndrome is an autoimmune disorder characterized by the
      association between antiphospholipid antibodies and venous or arterial thrombosis
      or obstetric complications. In spite of the recent progresses, many aspects of
      this disease remain unclear. In this review, we briefly focus on the most
      important advances in the pathophysiology, diagnosis and treatment of this
      condition.

PMID- 16085533
TI  - Instructed smoking expectancy modulates cue-elicited neural activity: a
      preliminary study.
AB  - In recent years, research applying functional neuroimaging to the study of cue
      elicited drug craving has emerged. This research has begun to identify a
      distributed system of brain activity during drug craving. A review of this
      literature suggested that expectations regarding the opportunity to use a drug
      affected the pattern of neural responses elicited by drug cues. Using functional
      magnetic resonance imaging (fMRI), we examined the effects of smoking expectancy
      on the neural response to neutral (e.g., roll of tape) and smoking-related (a
      cigarette) stimuli in male cigarette smokers deprived of nicotine for 8 hr. As
      predicted, several brain regions (e.g., the anterior cingulate cortex) exhibited
      differential activation during cigarette versus neutral cue exposure. Moreover,
      we found that subregions of the prefrontal cortex (i.e., ventromedial,
      ventrolateral, and dorsolateral prefrontal cortices) showed cue-elicited
      activation that was modulated by smoking expectancy. These results highlight the
      importance of perceived drug use opportunity in the neurobiological response to
      drug cues.

PMID- 16085538
TI  - Fondaparinux: a potential new therapy for HIT.
AB  - Heparin has been the mainstay of treatment and prevention of venous and arterial
      thromboembolism for many years. Its use, however, is associated with a serious
      and potentially fatal immunological drug reaction termed heparin-induced
      thrombocytopenia (HIT). Current treatment consists of discontinuing heparin
      therapy and the administration of an alternate anticoagulant (e.g. danaparoid,
      lepirudin, bivalirudin or argatroban). Fondaparinux is a novel synthetic heparin
      pentasaccharide capable of inhibiting factor Xa via the action of antithrombin
      (AT) but devoid of anti-factor IIa (thrombin) activity. Although the drug is
      identical in structure to the pentasaccharide domain found on unfractionated
      heparin (UH), it is too small to be recognized by the majority of heparin
      reactive antibodies. It is theoretically an excellent candidate agent for the
      treatment of HIT. Currently, fondaparinux is licensed for orthopaedic venous
      thromboprophylaxis but not for the treatment of HIT. Successes in the use of
      fondaparinux in the treatment of HIT, as demonstrated in recent published case
      reports, warrant further study in larger controlled trials for this indication.

PMID- 16085539
TI  - Cytomegalovirus-induced thrombocytopenia in an immunocompetent adult effectively
      treated with intravenous immunoglobulin: a case report and review.
AB  - The authors report the case of an 80-year-old male patient who presented with
      colitis and severe thrombocytopenia. The work-up revealed concurrent
      cytomegalovirus infection. After failure of prednisone, a single infusion of high
      dose intravenous immunoglobulin produced a rapid and sustained response.
      Seventeen cases from the world literature are reviewed. Corticosteroids seem
      effective in about one third of cases. In those who do not respond, splenectomy
      is relatively ineffective and more specific anti-CMV treatment with ganciclovir
      is of unproven efficacy and toxic, in view of the relatively favourable long term
      outcome the authors recommend intravenous immunoglobulin in cases of severe
      bleeding or when the platelet level is under 10 x 10(9) l.

PMID- 16085540
TI  - Gene expression profiling in the myelodysplastic syndromes.
AB  - The myelodysplastic syndromes (MDS) are a heterogeneous group of haematopoietic
      malignancies, characterized by blood cytopenias, ineffective hematopoiesis and
      hypercellular bone marrow. Several genetic alterations have been reported in MDS
      but these are not MDS-specific and the underlying molecular causes of the disease
      remain poorly understood. Gene expression microarray technology allows the
      simultaneous parallel analysis of many thousands of genes and has already
      provided novel insights into cancer pathogenesis. In this review we discuss the
      results of several recent studies which utilize the enormous power of microarray
      technology for the study of MDS. Several exciting findings have emerged from
      these early studies that highlight the potential of this technology to further
      our understanding of the molecular pathogenesis of this disorder. It is clear,
      however, that these findings should be confirmed in larger sets of MDS patients.

PMID- 16085541
TI  - Donor hematopoietic cells from transgenic mice that express GFP are immunogenic
      in immunocompetent recipients.
AB  - OBJECTIVE: To study the immunogenicity of hematopoietic cells marked with green
      fluorescence protein (GFP) while avoiding the potentially confounding effects of
      viral gene transduction, marked cells from GFP+ transgenic mice were tracked
      after transplantation into unconditioned immunocompetent recipients. MATERIALS
      AND METHODS: Marrow was harvested from GFP+ transgenic mice that had been crossed
      onto a BALB/cByJ background. Unconditioned marrow transplantation involved
      infusion of sex-matched or sex-mismatched cells into female BALB/cByJ hosts.
      Engraftment and contribution to circulating nucleated blood cells were compared
      to recipients of donor cells that were not GFP-marked. Donor cells were detected
      by flow cytometry (GFP) and fluorescence in situ hybridization (FISH) for Y
      chromosome sequences. RESULTS: Donor cells from mice of the same genetic
      background that did not express GFP were detected for more than four-weeks in
      unconditioned recipients. In contrast, GFP-marked cells in the blood peaked at
      one-week, declined to undetectable levels by two-weeks and were not detected in
      the marrow at sacrifice. In sex-mismatched studies, detection of male GFP+ donor
      cells by FISH yielded levels similar to those observed by flow cytometry, in
      contrast to the levels detected for many weeks in mice infused with male cells
      that did not express GFP. In immunocompetent recipients immunized with irradiated
      GFP-expressing cells, rechallenge with GFP+ cells resulted in the accelerated
      loss of donor cells. CONCLUSION: Donor marrow cells from GFP+ transgenic mice
      were lost after infusion into unconditioned immunocompetent mice and
      sensitization studies infer an immunologic mechanism. These results are similar
      to studies of virally transduced cells. Thus, infusion of cells with optimum
      engraftment potential could not compensate for the loss of donor cells due to
      immunogenicity.

PMID- 16085542
TI  - Recent thymic output function in patients with hematological malignancy.
AB  - Thymic function is important for the generation of T-cell diversity in the
      periphery of both children and adults during both health and disease. Until
      recently, thymic function could not be monitored, as a consequence of the absence
      of adequate technology to differentiate recent thymic emigrants (RTEs) from naive
      T cells. The generation of TCR diversity occurs in the thymus through
      recombination of gene segments encoding the variable parts of the TCR alpha and
      beta chains. During these processes, by-products of the rearrangements are
      generated in the form of signal joint T-cell receptor excision circles (sjTRECs).
      As sjTRECs are stable extrachromosomal DNA fragments, they are not replicated
      during mitosis and thus diluted with each round of cell division, and are
      therefore most frequent in naive T cells that have recently left the thymus,
      their quantification is actually considered as a valuable tool to estimate thymic
      function. Therefore, quantitative sjTRECs content have been recently used to
      assess thymic output during both health and disease. In this review, we summarize
      recent data on the recent thymic output function feature in patients with
      hematological malignancy and the immune reconstitution after stem cell
      transplantation and we also characterize factors that may improve the thymic
      output function.

PMID- 16085543
TI  - KDR and Sema3 genes expression in bone marrow stromal cells and hematopoietic
      cells from leukemia patients and normal individuals.
AB  - Kinase domain receptor (KDR) and Semaphorin3 (Sema3) have a functional
      relationship and are expressed in human bone marrow (BM). We cultured in vitro
      bone marrow stromal cells (BMSCs) and collected nonadherent cells from patients
      with acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), acute
      lymphoblastic leukemia (ALL) and normal individuals. Reverse transcriptase
      polymerase chain reaction enzyme-linked immunosorbent assay (RT-PCR-ELISA) was
      performed to examine KDR and Sema3 genes expression, using beta2 microglobulin as
      an internal reference. KDR expression ratio in normal control BMSCs (97.0%,
      32/33) was higher than in its corresponding nonadherent cells (70.8%, 17/24). KDR
      expression levels in ALL BMSCs and AML nonadherent cells were significantly
      higher than in normal controls. Sema3 expression ratios in nonadherent cells from
      AML (78.6%, 11/14) and CML (71.4%, 10/14) were both significantly lower than in
      normal control (100%, 27/27), its expression levels were also significantly lower
      than in normal control. Sema3 expression level in normal BMSCs was significantly
      lower than in nonadherent cells. Sema3 and KDR genes expression levels displayed
      a significantly positive correlation in normal control and ALL nonadherent cells
      (r=0.703, P=0.002; r=0.999, P=0.001). These results suggests that KDR may play a
      critical role in sustaining the hematopoietic microenvironment due to its high
      expression, and that KDR may be involved in pathogenesis of AML and ALL. Sema3
      could also sustain the survival of hematopoietic cells with its high expression,
      while Sema3 gene expression may be inhibited in AML and CML.

PMID- 16085544
TI  - Vincristine resistance development in lymphoblastoid cells under conditions of
      selective P-glycoprotein inhibition.
AB  - Most studies looking at the reversal of drug resistance in hematological
      malignancies have focused on the blockade of P-glycoprotein (Pgp) pump activity,
      as one of the more important proteins involved in cell resistance to the
      chemotherapeutic agents used. In model experiments using the IM-9 lymphoblastoid
      cell line cultured with increasing doses of vincristine (Vcr) in the presence or
      absence of the Pgp blocker cyclosporin A (CsA) we established two Vcr resistant
      sublines. By measuring Pgp expression in target cells, and the activity and
      sensitivity to cytostatics we believe that our results suggest the presence of
      other mechanisms involved in cell resistance to xenobiotics and that these
      mechanisms should be considered in the development of clinical trials designed to
      overcome drug resistance.

PMID- 16085545
TI  - Clonogenic growth patterns correlate with chemotherapy response in acute myeloid
      leukaemia.
AB  - Cytosine arabinoside and anthracycline-containing regimens induce remission in
      upwards of 60% of previously untreated patients with adult acute myeloid
      leukaemia (AML). Despite this, in addition to primary drug resistance, the
      majority of these patients relapse. Reliable methods for uniformly recognising
      these two subgroups at presentation do not exist and therefore a further attempt
      has been made to relate in vitro toxicity, using a clonogenic assay, to clinical
      outcome. In 10 normal controls and 12 chemotherapy naive cases, mononuclear cells
      harvested by density gradient separation were re-suspended at a concentration of
      2 x 10(5)/ml and quadruplicates of 250 microl per well cultured in methycellulose
      containing foetal calf serum and phytohaemagglutinin stimulated leucocyte
      conditioned medium. Cell kill was determined for cytosine arabinoside,
      daunorubicin and etoposide either singly or in combination using both a pulsed
      and continuous exposure. Aggregates were scored after seven days and three
      distinct patterns recognised. The patients all received the same drugs in a
      standard protocol and achievement of complete remission correlated with growth
      pattern. The survival of normal marrow colony-forming cells or GM-CFUc and the
      leukemic equivalent designated L-CFUc were assessed and a sensitivity index (SI)
      determined as a ratio of these two values in which more reproducible results were
      found when the drug was continuously present. It is concluded that the
      microculture technique is feasible and clearly demonstrates chemotherapy effect
      but no correlation was demonstrated with clinical outcome. This is a negative
      pilot study and, as a means of recognising drug sensitivity or resistance, should
      be discarded in favour of currently available molecular techniques.

PMID- 16085546
TI  - Low turnover bone disease in Egyptian children with acute leukemia.
AB  - The aim of this work was to study bone turnover markers, calcium homeostasis and
      bone mineral density (BMD) in children with acute leukemia at diagnosis, after
      induction chemotherapy, and during maintenance therapy to delineate abnormalities
      present. After evaluation of L2-L4 BMD using dual-energy X-ray absorptiometry in
      patients with acute myeloid and lymphoid leukemia at presentation and after
      treatment, the results were compared to 352 healthy age- and sex-matched Egyptian
      controls. Calcium homeostasis parameters and bone turnover biochemical markers
      (serum osteocalcin and urinary deoxypyridinoline) were also assayed and the
      results were compared to 12 healthy age- and sex-matched controls. Osteopenia was
      observed at diagnosis and during treatment in patients with acute leukemia. At
      diagnosis osteopenia was observed in 27 patients (62.8%): 10 (23.3%) had non
      severe osteopenia and 17 (39.5%) had severe osteopenia. This low BMD persisted in
      those who were followed up. Parathyroid hormone (PTH) (pg/ml) levels demonstrated
      non significant differences between children with acute leukemia at different
      stages of therapy and controls, while, 25 (OH) D3 (ng/ml) was significantly lower
      in acute leukemia patients at different stages of therapy compared to controls
      (p<0.001). Osteocalcin (ng/ml) is significantly lower in patients at different
      stages of the disease compared to controls (p<0.001) but there was no significant
      difference between patients at different stages of therapy. Deoxy-pyridoline
      cross links showed non-significant difference between the different types of
      acute leukemia and with controls. Osteopenia is a significant problem in children
      with acute leukemia at presentation and after chemotherapy. Osteopenia in acute
      leukemia appears to be of the low turnover type (decreased osteoblastic activity
      and decreased bone mineralization).

PMID- 16085547
TI  - Tc99m-sestaMIBI uptake in nonsecretory multiple myeloma.
AB  - Staging and monitoring of multiple myeloma (MM) is mainly based on monoclonal
      component quantification; the absence of such a parameter renders difficult
      follow up of patients with nonsecretory MM (nsMM). In this study our aims were to
      determine the specificity and sensitivity of Tc99m-sestaMIBI scintigraphy at
      diagnosis and during follow up of nsMM patients. Nine nsMM patients were
      prospectively studied at diagnosis and during treatment for a mean time of 33
      months (range: 12-65+). Tc99m-sestaMIBI (MIBI) scintigraphy was compared to
      conventional imaging (CI: X ray with CAT or NMR details) at diagnosis and during
      follow up. At diagnosis, CI and MIBI were concordant in three patients; CI showed
      more focal lesions than MIBI in four patients, while MIBI revealed more focal
      lesions than CI in two patients. During the follow up, MIBI uptake was normal in
      the four patients who achieved remission. Five patients did not achieve
      remission: CI and MIBI were concordant in three, while MIBI was falsely negative
      in two patients. In conclusion, Tc99m-sestaMIBI scintigraphy has high sensitivity
      (no false positive cases) and 78% specificity (2/9 false negative cases) in
      tracing active nsMM lesions; it should be considered complementary to CI for
      monitoring this rare disease.

PMID- 16085548
TI  - Divalent metal transporter 1.
AB  - In the last few years, the field of iron metabolism has exploded with the
      discovery of many new proteins including ferroportin, hephaestin, hepcidin,
      duodenal cytochrome b and the topic of this review, divalent metal ion
      transporter 1 (DMT1). DMT1 functions in transport of ferrous iron, and some, but
      not all divalent metal ions across the plasma membrane and/or out of the
      endosomal compartment. DMT1 mRNA has been found in every cell type in which it
      has been sought and its structure is highly conserved in evolution with similar
      proteins expressed in plants, insects, microorganisms and vertebrate animals.
      Rodents with defects in iron absorption and utilization were identified long
      before it was determined that the defect was due to a single nucleotide mutation
      in DMT1. Study of these animals reveals that transport of iron and other divalent
      metal ions by DMT1 is pH dependent, but the exact manner in which pH exerts its
      effect is unknown. The structure of the DMT1 gene is complex. Alternative usage
      of 3' exons, results in forms with and without iron responsive elements (IREs),
      while alternative usage of 5' exons and less well defined products of alternative
      splicing results in an array of isoforms with incompletely defined function.
      Expression of some isoforms is tissue specific and appears to affect subcellular
      targeting of the protein. At least one signal for DMT1 expression appears to be
      intracellular iron status, however, other, as yet undefined signals may also
      contribute to DMT1 expression. Interestingly, DMT1 function may differ subtly
      between humans and other animals; the spontaneous DMT1 mutation found in mice and
      rats appears to limit iron uptake in the intestine and iron utilization in red
      cell precursors, whereas the only known human mutation has its primary effect on
      iron utilization by erythroid cells. The importance of DMT1 function at the level
      of the whole organism and the individual cell and mechanisms of its regulation on
      a molecular scale are only beginning to be understood; an appreciation of these
      process will lead to an understanding of the role of iron in various cellular
      processes and improved treatments for both anemia and iron-overload.

PMID- 16085549
TI  - Skin rash in a patient who underwent allogeneic bone marrow transplatation for
      AML.

PMID- 16085550
TI  - Anti-CD 40 monoclonal antibody.
AB  - Normal, bi-directional interactions between CD 40 and its natural ligand CD 154
      (CD 40 ligand) are central to the generation of both T cell-dependent, humoral
      immune responses and cytotoxic T-cell responses. CD 40 is expressed on a broad
      range of hematological and epithelial malignancies. The development of monoclonal
      antibodies directed against CD 40 allows effective targeting of malignant cells
      through multiple mechanisms that include the recruitment of immune effector
      mechanisms such as complement-dependent cytotoxicity and antibody-dependent
      cellular cytotoxicity, direct anti-proliferative effects on neoplastic cells and,
      importantly, by the activation of tumor-targeted cellular cytotoxicity. This
      review provides the background to the early clinical trial data that are now
      beginning to emerge for this potentially exciting new treatment approach.

PMID- 16085551
TI  - CD 33 as a target of therapy in acute myeloid leukemia: current status and future
      perspectives.
AB  - CD 33 is a myeloid cell surface antigen that is expressed on blast cells in acute
      myeloid leukemia (AML) in a majority of all patients regardless of age or subtype
      of disease. The antigen is also expressed on leukemic stem cells in many cases,
      but is not expressed on normal hematopoietic stem cells. In an attempt to improve
      therapy in AML, a CD 33-targeted drug has been developed. The drug, gemtucumab
      ozogamicin (GO; Mylotarg), consists of a humanized CD 33 antibody (hP 67.6), a pH
      dependent linker, and a highly potent chemotherapy agent, calicheamicin 1,2,
      dimethyl hydrazine dichloride. Based on its clinical activity, GO has been
      approved for application in chemotherapy-refractory AML in various countries and
      is effective as a mono-substance as well as in combination with conventional
      chemotherapy. However, despite high efficacy and a certain specificity for
      leukemic (as opposed to normal) stem cells, the drug does not work in all
      patients, and can produce significant side-effects, including veno-occlusive
      disease (VOD), especially in patients who undergo stem cell transplantation.
      These side-effects have to be balanced against the benefit of GO therapy in
      patients with relapsed or refractory AML.

PMID- 16085552
TI  - The importance of the telomere and telomerase system in hematological
      malignancies.
AB  - Telomeres are specialized chromosomal end structures composed of repeat TTAGGG
      sequences in humans. They shorten with each cell division and thus serve as the
      "mitotic clock" of the cell. One of their main functions is the maintenance of
      chromosomal integrity and their excessive shortening is associated with DNA
      instability. Telomerase, a unique reverse transcriptase, is inactive in most
      somatic human cells and is up-regulated in most cancer cells. Recently, the
      biology of the telomere/telomerase system has attracted much attention because of
      its possible role in carcinogenesis and aging. In this article we review the
      biology of this system and its relevance to normal and malignant hematopoietic
      cells. The biological, diagnostic and prognostic value of telomere/telomerase
      biology is discussed, as well as its potential future applications in cancer
      therapeutics.

PMID- 16085553
TI  - Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.
AB  - Malignant pleural effusion (MPE) in multiple myeloma (MM) is rare. Approximately
      80 cases have been reported. To delineate optimal treatment and prognostic
      variables in these patients, we reviewed 11 MM patients with MPE. MPE developed
      at median of 12 months from diagnosis of MM. All the patients had high-risk
      disease based on complex karyotypic abnormalities including deletions of
      chromosome-13 (n=9), elevated beta-2 microglobulin (B2M) (n=9), high C-reactive
      protein (CRP) (n=8), high plasma cell labeling index (n=5) or high LDH (n=5). A
      significant increase in B2M, LDH, and CRP was observed at the onset of MPE. The
      initial diagnosis of MPE was based on positive cytology (n=9), pleural fluid
      cIg/DNA (n=9) or pleural fluid cytogenetics (n=4). Pleural tissue infiltration
      was found on pleural biopsy and autopsy in one patient each. Systemic
      chemotherapy comprising dexamethasone, cyclophosphamide, etoposide and cisplatin
      (DCEP) (n=7) and pleurodesis (n=7) were effective in resolving MPE but survival
      was short. High dose chemotherapy with peripheral blood stem cell support for MPE
      in six patients conferred no clear survival advantage. These patients died at
      median of four months from onset of MPE. Patients with bone marrow complex
      karyotypic abnormalities including deletion-13 (n=9) had a shorter (median--18
      months) overall survival compared to patients with normal cytogenetics (median-
      38 months). MPE in patients with MM is often associated with high-risk disease
      including deletion 13 chromosomal abnormality and heralds a poor prognosis
      despite aggressive local and systemic treatment.

PMID- 16085554
TI  - Haemopoietic progenitor cell transplantation in patients with previous history of
      invasive fungal infection.
AB  - The aim of this retrospective study conducted between H.U. Marques de Valdecilla
      (Spain) and the Royal Marsden NHS Trust (UK) was to analyse the outcome of
      patients who underwent haemopoietic progenitor cell transplantation (HPCT) after
      a previous history of Invasive fungal infections (IFI). This study includes 27
      patients (15 autologous, 12 allogeneic). The diagnosis of IFI was
      microbiologically proven in 21 cases and only radiologically in six. Pre-HPCT
      treatment included intravenous antifungals in all and surgical excision in eight
      cases. All patients received post-HPCT antifungal prophylaxis. Median time from
      diagnosis of IFI to HPCT was 131 days. At median follow-up of 193 days, three
      patients (two allogeneic, one autologous) had relapse of IFI resulting in death
      in all cases. One of them had received TBI and two were receiving treatment for
      graft versus host disease. Each patient was receiving a different form of
      prophylaxis. Overall, seven patients are alive and disease-free. Ten patients
      died from disease progression and 10 from transplant-related toxicity, including
      IFI. In our experience, the risk of post-HPCT reactivation of a previous IFI is
      low (11%), so IFI should not be an absolute contraindication for HPCT. The
      combination of aggressive antifungal treatment for IFI and antifungal prophylaxis
      throughout HPCT reduces the probability of reactivation.

PMID- 16085555
TI  - Respiratory failure after stem cell transplantation: improved outcome with non
      invasive ventilation.
AB  - We retrospectively analyzed the efficacy of non-invasive ventilation in 35
      patients with acute hypoxemic respiratory failure after autologous or allogeneic
      stem cell transplantation (SCT). Non-invasive ventilation was delivered by a
      standard face mask or helmet. Decisions to intubate were made according to
      standard criteria. Between 1993 and 2003, 836 patients underwent an autologous or
      allogeneic bone marrow or SCT. Eighty-two patients developed respiratory failure.
      Of these, 47 patients were initially intubated and mechanically ventilated. None
      of these patients survived. Thirty-five patients initially underwent non-invasive
      ventilation at the bone marrow transplant unit. Seven of these patients survived
      and were discharged from the hospital (20%). Eleven of the 35 (31%) patients
      improved within the first 4 h of non-invasive ventilation with respect to
      oxygenation and were regarded as responders. Seven of these patients survived to
      hospital discharge (64%), while all non-responders died (P<0.001). In all
      survivors, the partial pressure of arterial oxygen (PaO2) improved after the
      initiation of non-invasive ventilation. In non-survivors, PaO2 improved in only 4
      of 28 patients (17%) (P<0.0001). Non-invasive ventilation in patients with acute
      respiratory failure after SCT could improve prognosis in a carefully selected
      group of patients.

PMID- 16085556
TI  - Serial measurement of serum C-reactive protein levels can identify patients at
      risk for severe complications following autologous stem cell transplantation.
AB  - The value of serum C-reactive protein (CRP) levels as a predictor of
      complications in neutropenic patients needs to be further defined. We sought to
      identify an association between severe complications and daily CRP levels
      measured in 104 multiple myeloma patients during the 3 week period following high
      dose melphalan and autologous transplant. Significantly higher mean CRP levels
      and CRP velocity of increase were observed among patients with severe
      complications. A cut-off point of 100 mg/l (CRP levels) and 15 mg/l/day (CRP
      velocity) identified patients likely to suffer severe complications with 86 and
      75% sensitivity, respectively. Prospective validation of this model is currently
      underway.

PMID- 16085557
TI  - Brief report: practicability and safety of amphotericin B deoxycholate as
      continuous infusion in neutropenic patients with hematological malignancies.
AB  - Fungal infections are a major cause of morbidity and mortality in patients with
      hematological malignancies. Candida and Aspergillus species are the most
      important opportunistic fungal pathogens in this patient population. Amphotericin
      B is the treatment of choice, but its administration is often hampered by severe
      side-effects, which may be reduced by continuous infusion of this drug. We
      describe 17 consecutive patients with hematological malignancies, suffering from
      fever of unknown origin with possible fungal infections, treated with
      amphotericin B as continuous infusion compared with a control group of 10
      patients treated with conventional rapid infusion of amphotericin B over 2 - 6 h.
      No acute side-effects or severe nephrotoxicity were observed during continuous
      infusion of amphotericin B. Target doses were reached faster in patients with
      continuous infusion of amphotericin B than in patients with rapid infusion. We
      conclude that continuous infusion of amphotericin B is safe in neutropenic
      patients with hematological malignancies.

PMID- 16085558
TI  - Disseminated intravascular coagulation complicating acute lymphoblastic leukemia:
      a study of childhood and adult cases.
AB  - A high incidence of disseminated intravascular coagulation (DIC) in adult
      patients with acute lymphoblastic leukemia (ALL) is reported. However, studies
      comprising both childhood and adult patients are sparse and the clinical
      relevance of DIC in ALL patients has been a conflicting issue. Coagulation
      profiles at presentation and within seven days after starting remission-induction
      therapy of 44 childhood and 51 adult ALL patients were studied. At presentation,
      two childhood (5%) and 11 adult (22%) patients had DIC (p<0.05). After starting
      therapy, four of 27 childhood (15%) and 14 of 33 adult (42%) patients screened
      for coagulopathy developed DIC (p<0.05). Overall, six of the 44 children (14%)
      and 25 of the 51 adults (49%) were complicated with DIC (p<0.001). In the adult
      cases, DIC was more frequently complicated with FAB subtype L2 than L1 (p<0.05).
      All hemorrhages seen in the childhood cases were minor hemorrhages. In the adult
      patients, two patients with DIC had WHO grade 3 hemorrhage and the other
      hemorrhagic complications were minor hemorrhages. While milder induction
      therapies starting with corticosteroid given for childhood cases should be taken
      into consideration when comparing the incidences of DIC after therapy, the
      findings indicated that childhood and adult ALL may differ in the procoagulant
      characteristics. Morphological distinction between L1 and L2 appears to have
      relevance in the procoagulant activity in adult ALL. DIC complicating ALL is
      generally mild, however, sometimes causes severe hemorrhages in adults.

PMID- 16085559
TI  - Serum Ca 125 levels in children with acute leukemia and lymphoma.
AB  - Ca 125 is a tumor marker for the diagnosis and monitoring of ovarian carcinoma.
      We investigated serum Ca 125 levels in 44 children with leukemia and 59 children
      with lymphoma at initial presentation and 4 weeks after chemotherapy. Serum Ca
      125 levels were measured chemilumimetrically with a sandwich enzyme-linked
      immunosorbent assay. The incidence of elevated serum Ca 125 levels was
      significantly higher in children with leukemia (14 children) and lymphoma (26
      children) than in the healthy children (2 children). In the patients with non
      Hodgkin's lymphoma (NHL) who had abdominal involvement and/or serous membrane
      involvement (ascides, pleural, pericardial effusion) at presentation, serum Ca
      125 levels were significantly higher than in the patients without abdominal
      and/or serosal involvement. Serum Ca 125 levels were impressively increased in
      the patients with Burkitt's lymphoma (BL) in whom abdominal and/or serous
      membrane involvement were observed more frequently than the other types of
      lymphoma. The increased serum Ca 125 levels in the patients returned to normal 4
      weeks after chemotherapy when they achieved complete remission. In conclusion,
      serum Ca 125 seems to be a good indicator for serous membrane involvement and it
      seems to be a promising tumor marker in the assessment of therapeutic response in
      children with leukemia and NHL.

PMID- 16085560
TI  - Secondary hematological malignancies after breast cancer chemotherapy.
AB  - According to several reports, the 10 year incidence of secondary acute
      myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after systemic
      chemotherapy is approximately 1.5%. The cumulative risk increases by 0.25--1% for
      the first 8 years after treatment. We have reported only 6 cases of hematological
      malignancies (0.3%) after breast cancer chemotherapy in our institute. We
      detected 2 cases of secondary AML and 1 case of MDS, 19, 52 and 12 months,
      respectively, after systemic chemotherapy for breast cancer. Published data on
      the occurrence of secondary hematological malignancies other than AML or MDS in
      this setting are scarce. We encountered diffuse large B-cell lymphoma,
      angioimmunoblastic lymphoma and mantle cell lymphoma as secondary hematological
      malignancies after systemic chemotherapy for breast cancer.

PMID- 16085561
TI  - Non-Hodgkin's lymphoma presenting as a breast mass in patients with HIV
      infection: a report of three cases.
AB  - Breast involvement with non-Hodgkin's lymphoma (NHL) is rare. Patients with AIDS
      have an increased incidence of NHL, often with high-grade histology, extranodal
      presentation and aggressive clinical course. Lymphoma of the breast in patients
      with HIV-1 infection has not been reported. We reviewed our tumor registry
      database of all AIDS-associated NHL and report on the clinical presentation and
      long-term outcome of 3 patients with AIDS who presented with lymphomatous
      involvement of the breast.

PMID- 16085562
TI  - Allergic reaction to chlorambucil in chronic lymphocytic leukemia presenting with
      fever and lymphadenopathy.
AB  - Chronic lymphocytic leukemia (CLL) is commonly treated with the alkylating agent
      chlorambucil. Allergic reactions to this chemotherapy are rare. Previous reports
      include urticaria, angioedema, rashes, toxic epidermal necrolysis, drug fever and
      one case of immune hemolytic anemia. We report 2 cases that had the identical
      symptoms of acute onset of high fever and progressive lymphadenopathy. These
      symptoms disappeared with conservative management. Neither of the patients were
      treated for infection or disease progression. When the patients were rechallenged
      with chlorambucil, identical reactions recurred. There was no cross-reactivity
      with the alkylating agent cyclophosphamide or other types of chemotherapy. This
      type of reaction to chlorambucil has not been described previously. It is
      important to recognize this as an allergic reaction. These reactions could be
      confused with the onset of infection, progression of disease or even a Richter's
      transformation.

PMID- 16085563
TI  - Troglitazone overcomes doxorubicin-resistance in resistant K562 leukemia cells.
AB  - Human myeloid leukemia cells become resistant to doxorubicin (DOX) treatment and
      this resistance is correlated with an increased glyoxalase 1 (GLO1) expression.
      Troglitazone (TRG) is an anti-diabetic thiazolidinedione drug previously used to
      treat insulin-resistance in Type 2 diabetes. We previously showed that TRG down
      regulates GLO1 gene expression in a number of cell types and reasoned that TRG
      might be a useful adjunct therapy to overcome DOX resistance. Here we show that
      TRG treatment overcomes the resistance to DOX in the DOX-resistant K562 human
      leukemia cells. Higher doses of TRG were found to alter histone H3:H2B ratios
      with a decreased ratio in DOX-sensitive and increased ratio in DOX-resistant
      lines. Furthermore, phosphorylated H3 was seen in DOX-resistant but not in DOX
      sensitive cells. We conclude that the downstream effect of TRG in DOX-resistant
      cells may be interference with normal cell cycle events leading to genomic
      instability. Our data suggest that TRG may be a useful adjunct therapy in
      circumventing drug resistance in K562 leukemia cells.

PMID- 16085564
TI  - The death receptor pathway is not involved in alloreactive T-cell induced
      mitochondrial membrane permeability.
AB  - Elimination of tumor cells by cytotoxic T lymphocytes (CTL) is mediated by two
      major pathways: the granule exocytosis and the death receptor pathway, transduced
      by Fas, TNF and TRAIL. The usage of these distinct pathways in the alloreactive
      setting across major and minor HLA barriers still remains controversial. We
      generated CTLs against allogeneic Epstein-Barr virus (EBV)-transformed cell lines
      (LCL) from HLA-unmatched healthy donors and assessed their cytotoxicity by flow
      cytometrically measuring mitochondrial membrane permeability (MMP) of target
      cells. Mitochondrial apoptosis induced by CTL was abrogated by selectively
      inhibiting the granule exocytosis-mediated pathway with Concanamycin A (CMA).
      Conversely, apoptosis was not decreased in the presence of the caspase 8
      inhibitor IETD, which is specific for all death receptor pathways. In general,
      caspases were not involved in MMP as shown using the pan-caspase inhibitor zVAD.
      This effector mechanism was preserved when using purified CD4 + and CD8 + T
      lymphocyte subsets to generate CTL. We further showed, that death receptor
      signalling was not used as a salvage mechanism when granule exocytosis was
      inhibited even at longer incubation times sufficient for slow kinetic death
      receptor caspase signalling. Our results clearly demonstrate that mitochondrial
      apoptosis induced by human alloreactive CTLs is mainly mediated by granule
      exocytosis but not by death receptor caspase dependent pathways. Furthermore, the
      granule exocytosis pathway does not require caspases to induce MMP.

PMID- 16085565
TI  - Sustained molecular remission by non-myeloablative stem cell transplantation
      after autologous hematopoietic stem cell transplantation in a patient with
      multiple myeloma.
AB  - Multiple myeloma (MM) is refractory to conventional chemotherapy. To achieve a
      sustained complete remission, we performed planned non-myeloablative allogeneic
      stem cell transplantation (NST) after autologous hematopoietic stem cell
      transplantation (HSCT) in a patient with stage III MM. Autologous HSCT was
      performed using high-dose melphalan after conventional chemotherapy, followed by
      NST from an HLA-identical sibling using low-dose total body irradiation (200 cGy)
      for conditioning. Cyclosporine and mycophenolate mofetil were used for graft-vs
      host disease (GVHD) prophylaxis. Acute GVHD was transiently seen in the skin and
      intestine, while, in addition, mild chronic GVHD was seen in the oral mucosa and
      skin. Complete donor chimerism was achieved and the disappearance of tumor
      derived monoclonal B cells was confirmed based on an analysis of immunoglobulin
      light chain messenger signals on day 156 when chronic GVHD occurred. The clinical
      course in this case strongly suggested the existence of a graft-vs-myeloma
      effect.

PMID- 16085566
TI  - Congenital MLL-positive B-cell acute lymphoblastic leukemia (B-ALL) switched
      lineage at relapse to acute myelocytic leukemia (AML) with persistent t(4;11) and
      t(1;6) translocations and JH gene rearrangement.
AB  - Congenital acute leukemia is a rare form of childhood leukemia, in which lineage
      conversion at relapse is very rarely reported. Here we describe a case of
      congenital B-cell acute lymphoblastic leukemia (B-ALL) with t(4;11) and t(1;6)
      translocations, which at relapse underwent a switch to monocytic lineage with
      persistence of the original cytogenetic translocations and clonal rearrangement
      of the JH gene. Similar to the other described cases of congenital acute leukemia
      with lineage conversion, our case had a MLL gene rearrangement and followed an
      aggressive clinical course.

PMID- 16085567
TI  - Successful treatment of hairy cell leukemia variant with rituximab.
AB  - Hairy cell leukemia (HCL) variant is a rare low-grade B-cell disorder affecting
      the elderly or middle-aged population with features intermediate between those of
      HCL and prolymphocytic leukemia. Unlike HCL, it is resistant to most conventional
      treatment. We report a case of a 53-year-old man who had refractory
      thrombocytopenia and lymphocytosis for 8 years. Investigations and analysis of
      spleen and bone marrow revealed a diagnosis of HCL variant. He opted for
      treatment with rituximab, a chimeric monoclonal antibody targeting CD 20. There
      was complete recovery of his full blood count and a bone marrow biopsy performed
      3 months post-treatment showed complete remission. This is, to our knowledge, the
      first reported patient with HCL variant for whom treatment with rituximab was
      successful, and this treatment needs further investigation.

PMID- 16085568
TI  - Secondary B-cell acute lymphoblastic leukemia following Wilms' tumor: clinical
      and in vitro chemosensitivity studies.
AB  - We report the clinical features and in vitro chemosensitivity assay findings of a
      13-year-old girl who developed secondary B-cell acute lymphoblastic leukemia
      (ALL) 7 years after a diagnosis of Wilms' tumor. The patient was treated using
      the Berlin - Frankfurt - Muenster (BFM) ALL chemotherapy protocol with poor
      response to initial therapy before succumbing to sepsis. An in vitro
      chemosensitivity assay on her peripheral blood lymphoblasts was performed while
      she was undergoing induction therapy and showed a high level of resistance to
      drugs commonly used for ALL therapy, e.g. steroids, anthracyclines, vincristine
      and L-asparaginase. The mechanism of chemoresistance was not elicited, but was
      probably not related to P-glycoprotein (P-gp) over-expression. We believe that
      the in vitro chemosensitivity assay is a good indicator of cellular response to
      chemotherapy and may provide reliable information for the basis of the selection
      of drugs to be used for the treatment of similarly rare patients rather than
      relying on "standard" protocols.

PMID- 16085569
TI  - Bilateral primary orbital non-Hodgkin's lymphoma in a patient with scleroderma: a
      case report.
AB  - Orbital presentation of non-Hodgkin's Lymphoma (NHL) is uncommon but occurs both
      as the only site of disease and as a site of recurrence. Primary orbital NHLs are
      usually low-grade, and mostly extranodal marginal zone/mucosa associated lymphoid
      tissue B-cell neoplasms. They are commonly associated with chronic inflammatory
      conditions. The issue of bilaterality in orbital lymphoma is not very common. The
      onset of malignant lymphoproliferation may precede, follow, or exist
      simultaneously with scleroderma. Different treatment modalities were applied in
      orbital NHL such as surgery, radiation therapy, chemotherapy or both. We report a
      57-year-old man with scleroderma presenting with eyelid hernias who had biopsy
      proven marginal zone NHL, successfully treated with radiotherapy and combined
      chemotherapy, and also review the literature.

PMID- 16085570
TI  - Severe aplastic anemia associated with paroxysmal nocturnal hemoglobinuria and
      lymphoplasmacytic lymphoma.
AB  - An unusual case of aplastic anemia presenting in association with
      lymphoplasmacytic lymphoma and paroxysmal nocturnal hemoglobinuria is discussed.
      An insult to the hematological stem cell compartment may result in multiple
      pathological entities, potentially influencing our approach to the treatment of
      hematological clonal disorders.

PMID- 16085571
TI  - Synchronous mucosa-associated lymphoid tissue (MALT) lymphomas involving
      bilateral orbits and breasts: a rare clinical entity.
AB  - Primary orbital and primary breast lymphomas comprise very small subgroups of
      extranodal lymphomas. Clinical presentation at both these sites together is
      extremely rare. We describe a case of bilateral orbital and bilateral breast
      mucosa-associated lymphoid tissue (MALT) lymphomas with bilateral pre-auricular
      lymph nodal metastasis. The case history, staging and management for this unusual
      entity are discussed.

PMID- 16085573
TI  - Integration of morphological data sets for phylogenetic analysis of Amniota: the
      importance of integumentary characters and increased taxonomic sampling.
AB  - Several mutually exclusive hypotheses have been advanced to explain the
      phylogenetic position of turtles among amniotes. Traditional morphology-based
      analyses place turtles among extinct anapsids (reptiles with a solid skull roof),
      whereas more recent studies of both morphological and molecular data support an
      origin of turtles from within Diapsida (reptiles with a doubly fenestrated skull
      roof). Evaluation of these conflicting hypotheses has been hampered by
      nonoverlapping taxonomic samples and the exclusion of significant taxa from
      published analyses. Furthermore, although data from soft tissues and anatomical
      systems such as the integument may be particularly relevant to this problem, they
      are often excluded from large-scale analyses of morphological systematics. Here,
      conflicting hypotheses of turtle relationships are tested by (1) combining
      published data into a supermatrix of morphological characters to address issues
      of character conflict and missing data; (2) increasing taxonomic sampling by more
      than doubling the number of operational taxonomic units to test internal
      relationships within suprageneric ingroup taxa; and (3) increasing character
      sampling by approximately 25% by adding new data on the osteology and histology
      of the integument, an anatomical system that has been historically
      underrepresented in morphological systematics. The morphological data set
      assembled here represents the largest yet compiled for Amniota. Reevaluation of
      character data from prior studies of amniote phylogeny favors the hypothesis that
      turtles indeed have diapsid affinities. Addition of new ingroup taxa alone leads
      to a decrease in overall phylogenetic resolution, indicating that existing
      characters used for amniote phylogeny are insufficient to explain the evolution
      of more highly nested taxa. Incorporation of new data from the soft and osseous
      components of the integument, however, helps resolve relationships among both
      basal and highly nested amniote taxa. Analysis of a data set compiled from
      published sources and data original to this study supports monophyly of Amniota,
      Synapsida, Reptilia, Parareptilia, Eureptilia, Eosuchia, Diapsida, Neodiapsida,
      Sauria, Lepidosauria, and Archosauriformes, as well as several more highly nested
      divisions within the latter two clades. Turtles are here resolved as the sister
      taxon to a monophyletic Lepidosauria (squamates + Sphenodon), a novel
      phylogenetic position that nevertheless is consistent with recent molecular and
      morphological studies that have hypothesized diapsid affinities for this clade.

PMID- 16085574
TI  - Simultaneous statistical multiple alignment and phylogeny reconstruction.
AB  - Although the reconstruction of phylogenetic trees and the computation of multiple
      sequence alignments are highly interdependent, these two areas of research lead
      quite separate lives, the former often making use of stochastic modeling, whereas
      the latter normally does not. Despite the fact that reasonable insertion and
      deletion models for sequence pairs were already introduced more than 10 years
      ago, they have only recently been applied to multiple alignment and only in their
      simplest version. In this paper we present and discuss a strategy based on
      simulated annealing, which makes use of these models to infer a phylogenetic tree
      for a set of DNA or protein sequences together with the sequences'indel history,
      i.e., their multiple alignment augmented with information about the positioning
      of insertion and deletion events in the tree. Our method is also the first
      application of the TKF2 model in the context of multiple sequence alignment. We
      validate the method via simulations and illustrate it using a data set of primate
      mtDNA.

PMID- 16085575
TI  - Phylogenetic signal in bone microstructure of sauropsids.
AB  - In spite of the fact that the potential usefulness of bone histology in
      systematics has been discussed for over one and a half centuries, the presence of
      a phylogenetic signal in the variation of histological characters has rarely been
      assessed. A quantitative assessment of phylogenetic signal in bone histological
      characters could provide a justification for performing optimizations of these
      traits onto independently generated phylogenetic trees (as has been done in
      recent years). Here we present an investigation on the quantification of the
      phylogenetic signal in the following bone histological, microanatomical, and
      morphological traits in a sample of femora of 35 species of sauropsids: vascular
      density, vascular orientation, index of Haversian remodeling, cortical thickness,
      and cross-sectional area (bone size). For this purpose, we use two methods,
      regressions on distance matrices tested for significance using permutations (a
      Mantel test) and random tree length distribution. Within sauropsids, these bone
      microstructural traits have an optimal systematic value in archosaurs. In this
      taxon, a Mantel test shows that the phylogeny explains 81.8% of the variation of
      bone size and 86.2% of the variation of cortical thickness. In contrast, a Mantel
      test suggests that the phylogenetic signal in histological traits is weak:
      although the phylogeny explains 18.7% of the variation of vascular density in
      archosaurs, the phylogenetic signal is not significant either for vascular
      orientation or for the index of Haversian remodeling. However, Mantel tests seem
      to underestimate the proportion of variance of the dependent character explained
      by the phylogeny, as suggested by a PVR (phylogenetic eigenvector) analysis. We
      also deal with some complementary questions. First, we evaluate the functional
      dependence of bone vascular density on bone size by using phylogenetically
      independent contrasts. Second, we perform a variation partitioning analysis and
      show that the phylogenetic signal in bone vascular density is not a by-product of
      phylogentic signal in bone size. Finally, we analyze the evolution of cortical
      thickness in diapsids by using an optimization by squared change parsimony and
      discuss the functional significance of this character in terms of decreased
      buoyancy in crocodiles and mass saving in birds. These results are placed in the
      framework of the constructional morphology model, according to which the
      variation of a character in a clade has a historical (phylogenetic) component, a
      functional (adaptive) component, and a structural (architectural) component.

PMID- 16085576
TI  - Evolutionary rates analysis of Leguminosae implicates a rapid diversification of
      lineages during the tertiary.
AB  - Tertiary macrofossils of the flowering plant family Leguminosae (legumes) were
      used as time constraints to estimate ages of the earliest branching clades
      identified in separate plastid matK and rbcL gene phylogenies. Penalized
      likelihood rate smoothing was performed on sets of Bayesian likelihood trees
      generated with the AIC-selected GTR+ Gamma +I substitution model. Unequivocal
      legume fossils dating from the Recent continuously back to about 56 million years
      ago were used to fix the family stem clade at 60 million years (Ma), and at 1-Ma
      intervals back to 70 Ma. Specific fossils that showed distinctive combinations of
      apomorphic traits were used to constrain the minimum age of 12 specific internal
      nodes. These constraints were placed on stem rather than respective crown clades
      in order to bias for younger age estimates. Regardless, the mean age of the
      legume crown clade differs by only 1.0 to 2.5 Ma from the fixed age of the legume
      stem clade. Additionally, the oldest caesalpinioid, mimosoid, and papilionoid
      crown clades show approximately the same age range of 39 to 59 Ma. These findings
      all point to a rapid family-wide diversification, and predict few if any legume
      fossils prior to the Cenozoic. The range of the matK substitution rate, 2.1-24.6
      x 10(-10) substitutions per site per year, is higher than that of rbcL, 1.6- 8.6
      x 10(-10), and is accompanied by more uniform rate variation among codon
      positions. The matK and rbcL substitution rates are highly correlated across the
      legume family. For example, both loci have the slowest substitution rates among
      the mimosoids and the fastest rates among the millettioid legumes. This explains
      why groups such as the millettioids are amenable to species-level phylogenetic
      analysis with these loci, whereas other legume groups are not.

PMID- 16085577
TI  - CT in PET/CT: essential features of interpretation.

PMID- 16085578
TI  - When the heart loses its nerves...and how nuclear imaging helps to understand.

PMID- 16085579
TI  - Potential and pitfalls of therapy with alpha-particles.

PMID- 16085580
TI  - Quantification of left ventricular volumes and ejection fraction from gated 99mTc
      MIBI SPECT: MRI validation and comparison of the Emory Cardiac Tool Box with QGS
      and 4D-MSPECT.
AB  - The goal of this study was to validate the accuracy of the Emory Cardiac Tool Box
      (ECTB) in assessing left ventricular end-diastolic or end-systolic volume (EDV,
      ESV) and ejection fraction (LVEF) from gated (99m)Tc-methoxyisobutylisonitrile
      ((99m)Tc-MIBI) SPECT using cardiac MRI (cMRI) as a reference. Furthermore,
      software-specific characteristics of ECTB were analyzed in comparison with 4D
      MSPECT and Quantitative Gated SPECT (QGS) results (all relative to cMRI).
      METHODS: Seventy patients with suspected or known coronary artery disease were
      examined using gated (99m)Tc-MIBI SPECT (8 gates/cardiac cycle) 60 min after
      tracer injection at rest. EDV, ESV, and LVEF were calculated from gated (99m)Tc
      MIBI SPECT using ECTB, 4D-MSPECT, and QGS. Directly before or after gated SPECT,
      cMRI (20 gates/cardiac cycle) was performed as a reference. EDV, ESV, and LVEF
      were calculated using Simpson's rule. RESULTS: Correlation between results of
      gated (99m)Tc-MIBI SPECT and cMRI was high for EDV (R = 0.90 [ECTB], R = 0.88 [4D
      MSPECT], R = 0.92 [QGS]), ESV (R = 0.94 [ECTB], R = 0.96 [4D-MSPECT], R = 0.96
      [QGS]), and LVEF (R = 0.85 [ECTB], R = 0.87 [4D-MSPECT], R = 0.89 [QGS]). EDV
      (ECTB) did not differ significantly from cMRI, whereas 4D-MSPECT and QGS
      underestimated EDV significantly compared with cMRI (mean +/- SD: 131 +/- 43 mL
      [ECTB], 127 +/- 42 mL [4D-MSPECT], 120 +/- 38 mL [QGS], 137 +/- 36 mL [cMRI]).
      For ESV, only ECTB yielded values that were significantly lower than cMRI. For
      LVEF, ECTB and 4D-MSPECT values did not differ significantly from cMRI, whereas
      QGS values were significantly lower than cMRI (mean +/- SD: 62.7% +/- 13.7%
      [ECTB], 59.0% +/- 12.7% [4DM-SPECT], 53.2% +/- 11.5% [QGS], 60.6% +/- 13.9%
      [cMRI]). CONCLUSION: EDV, ESV, and LVEF as determined by ECTB, 4D-MSPECT, and QGS
      from gated (99m)Tc-MIBI SPECT agree over a wide range of clinically relevant
      values with cMRI. Nevertheless, any algorithm-inherent over- or underestimation
      of volumes and LVEF should be accounted for and an interchangeable use of
      different software packages should be avoided.

PMID- 16085581
TI  - Quantitative dynamic cardiac 82Rb PET using generalized factor and compartment
      analyses.
AB  - We have addressed 2 major challenges of (82)Rb cardiac PET, noninvasive
      estimation of an accurate input function and absolute quantitation of myocardial
      perfusion, using a generalized form of least-squares factor analysis of dynamic
      sequences (GFADS) and a novel compartment analysis approach. METHODS: Left and
      right ventricular (LV + RV) time-activity curves (TACs) were generated from 10
      rest/stress studies, and 30 myocardial TACs were modeled to cover a range of
      clinical values. Two-dimensional PET Monte Carlo simulations of the LV, RV,
      myocardium, and other organs were generated separately and combined using the
      above TACs to form 30 realistic dynamic (82)Rb studies. LV and RV TACs were
      estimated by GFADS and used as input to a 2-compartment kinetic analysis that
      estimates parametric maps of myocardial tissue extraction (k(1)) and egress
      (k(2)), as well as LV + RV contributions (f(v), r(v)), by orthogonal voxel
      grouping. In addition, 13 patients were injected with 2.22 +/- 0.19 GBq (60 +/- 5
      mCi) of (82)Rb and imaged dynamically for 6 min at rest and during dipyridamole
      stress. RESULTS: In Monte Carlo simulations, GFADS yielded estimates of the 3
      factors and corresponding factor images, with average errors of -4.2% +/- 6.3%,
      3.5% +/- 4.3%, and 2.0% +/- 5.5% in the LV, RV, and myocardial factor estimates,
      respectively. The estimates were significantly more accurate and robust to noise
      than those obtained using TACs based on manually drawn volumes of interest (P <
      0.01). The 2-compartment approach yielded accurate k(1), k(2), f(v), and r(v)
      parametric maps; the average error of estimates of k(1) was 6.8% +/- 3.6%. In all
      patient studies, our approach yielded robust estimates of k(1), k(2), f(v), and
      r(v), which correlated very well with the status of the subject and the
      catheterization results. CONCLUSION: Quantitative dynamic (82)Rb PET using
      generalized factor analysis of dynamic sequences and compartmental modeling
      yields estimates of parameters of absolute myocardial perfusion and kinetics with
      errors of <9%.

PMID- 16085582
TI  - Novel doppler assessment of intracoronary volumetric flow reserve: validation
      against PET in patients with or without flow-dependent vasodilation.
AB  - Volumetric blood flow (Q) determination requires simultaneous assessment of mean
      blood flow velocity and vessel cross-sectional area. At present, no method
      provides both values. Intracoronary Doppler-based assessment of coronary flow
      velocity reserve (CFVR) relies on average peak velocity (APV). Because this does
      not account for changes in velocity profile or vessel area usually occurring with
      flow-dependent vasodilation, results can be misleading. The aim of this clinical
      study was to validate against the current gold standard (measurement of
      myocardial perfusion reserve [MPR] by PET) a new, Doppler-based method for
      calculating coronary Q and coronary flow reserve (CFR). METHODS: Doppler-based
      intracoronary Q was measured with a proprietary guidewire device in a nonstenotic
      coronary artery at baseline and during adenosine-induced hyperemic flow (140
      mug/kg/min intravenously during 7 min). Three gate positions were assessed, of
      which 2 were lying within the vessel and 1 was intersecting the vessel. The
      zeroth (M(0)) and the first (M(1)) Doppler moments of the intersecting gate were
      used to calculate mean blood flow velocity (M(1)/M(0)) and vessel area (M(0)),
      and M(0) of the 2 proximal gates was used to correct for scattering and
      attenuation. CFR was calculated as hyperemic/resting flow with Q and compared
      with APV-derived CFVR and with the corresponding segmental MPR obtained with
      (15)O-labeled water and PET. RESULTS: Q (CFR, 2.60 +/- 1.07) correlated well with
      PET (MPR, 2.58 +/- 1.11) (r = 0.832, P < 0.005; Bland-Altman limits, -1.42 to
      1.09), whereas CFVR did not (r = 0.09, P = not statistically significant; Bland
      Altman limits, -3.36 to 2.24). However, in vessels without dilation, there was no
      difference between CFR, CFVR, and MPR. CONCLUSION: This procedure for
      intracoronary Q measurement using the proprietary Doppler guidewire system, which
      accounts for both changes in flow profile and changes in vessel area, allows
      invasive, accurate assessment of CFR even in the presence of flow-dependent
      vasodilation.

PMID- 16085583
TI  - Association of vascular 18F-FDG uptake with vascular calcification.
AB  - Both calcification and FDG uptake have been advocated as indicators of atheroma.
      Atheromas calcify as cells in the lesion undergo apoptosis and necrosis during
      evolution of the lesion and at the end stage of the lesion. FDG concentrates in
      lesions due to the relatively dense cellularity in regions of inflammation of
      active atheromas. This investigation examines the geographic relationship of
      focal vascular (18)F-FDG uptake, as a marker of atherosclerotic inflammation, to
      arterial calcification detected by contemporaneous CT. METHODS: We reviewed
      PET/CT images from 78 patients who were referred for tumor staging for the
      presence of vascular (18)F-FDG uptake and vascular calcification. Arterial wall
      (18)F-FDG accumulation greater than adjacent blood-pool activity was considered
      inflammation. Arterial attenuation of >130 Hounsfield units was considered
      calcification. Sites in the ascending and descending aorta, the carotid and iliac
      arteries, and the coronary territories were examined on the emission, CT, and
      fusion images on a point-by-point basis. When lesions were seen, we evaluated
      whether they were overlapping or discrete. RESULTS: The (18)F-FDG arterial
      distribution was consistent with established atherosclerotic topography, with
      increased uptake in the thoracic aorta, at the carotid bifurcation, and in the
      proximal coronary vessels. Arteries typically displayed a patchwork of normal
      vessel, focal inflammation, or calcification; inflammation and calcification
      overlapped in <2% of cases. Arterial inflammation preceded calcification, in
      terms of mean patient age. Coronary inflammation was more prevalent in patients
      with more cardiovascular risk factors. CONCLUSION: Vascular calcification and
      vascular metabolic activity rarely overlap, suggesting these findings represent
      different stages in the evolution of atheroma.

PMID- 16085584
TI  - Baseline/postnitrate tetrofosmin SPECT for myocardial viability assessment in
      patients with postischemic severe left ventricular dysfunction: new evidence from
      MRI.
AB  - The aim of this study was to compare (99m)Tc-tetrofosmin SPECT with contrast
      enhanced MRI (ceMRI), a new direct sign of myocardial fibrosis. METHODS: We
      studied 21 patients (age, 60 +/- 11 y; 19 male) with previous myocardial
      infarction and severe left ventricular dysfunction (ceMRI EF, 29% +/- 6%). All
      patients underwent resting and postnitrate (intravenous isosorbide dinitrate)
      (99m)Tc-tetrofosmin gated SPECT as well as ceMRI. Scintigraphic analysis was
      performed using quantitative perfusion SPECT (QPS), providing the percentage
      radiotracer uptake and defect severity in a 20-segment model. Hyperenhancement
      was defined by the increase of ceMRI signal intensity 20 min after intravenous
      injection of gadolinium-diethylenetriaminepentaacetic acid and its regional
      extension as the percentage of the total segment area. RESULTS: In ceMRI
      dysfunctional segments, the correlation between the extent of hyperenhancement
      and both (99m)Tc-tetrofosmin uptake and defect severity was significantly better
      after nitrate administration rather than at rest (P < 0.0001). Using a ceMRI
      cutoff below 40%, 102 of 196 (52%) segments were viable, whereas 94 (48%)
      segments were not viable. According to receiver-operating characteristic curve
      analysis, diagnostic accuracies were higher for postnitrate (99m)Tc-tetrofosmin
      uptake as well as perfusion defect severity than using resting data (0.84 vs.
      0.71, P < 0.001; 0.89 vs. 0.76, P < 0.001, respectively). CONCLUSION: After
      nitrate administration, (99m)Tc-tetrofosmin uptake and perfusion defect severity
      were closely related to ceMRI, demonstrating, in vivo, the existence of an
      inverse correlation between the transmural distribution of fibrosis and tracer
      delivery to the myocardium.

PMID- 16085585
TI  - Comparison of spiral multidetector CT angiography and myocardial perfusion
      imaging in the noninvasive detection of functionally relevant coronary artery
      lesions: first clinical experiences.
AB  - Compared with conventional coronary angiography, spiral multidetector CT (MDCT)
      angiography has delivered promising accuracy in the detection and validation of
      coronary lesions. Myocardial perfusion imaging (MPI) using SPECT is an
      established method for noninvasively assessing the functional significance of
      coronary stenoses and delivers valuable information for risk stratification. This
      retrospective analysis compared the accuracies of MDCT angiography and MPI in the
      detection of hemodynamically relevant lesions of the coronary arteries. METHODS:
      Twenty-five patients with suspected or known coronary artery disease were
      studied. Electrocardiographically gated MPI and 16-MDCT angiography were
      performed. Myocardial perfusion images were analyzed by 2 experienced observers,
      and reversible and fixed perfusion defects were detected and allocated to their
      corresponding coronary vessels. For the evaluation of MDCT angiography, image
      quality was determined, and lesions > or = 50% and luminal narrowing < 50% were
      visually assessed and characterized by 2 independent observers unaware of the
      results of MPI. RESULTS: Ninety-nine coronary vessels were analyzed, and the
      quality of MDCT angiography images was assessed for 330 coronary segments.
      Coronary artery diameter was interpretable for 231 (70%) of 330 segments, whereas
      in 99 (30%) of 330 segments, vessel diameter could not be evaluated because of
      heavy calcifications, blurring, motion artifacts, or intracoronary stents. MDCT
      angiography detected stenoses > or = 50% in 15 of 100 coronary arteries. Eight
      (53%) of 15 stenoses > or = 50% showed reversible or fixed perfusion defects in
      the corresponding myocardial areas on MPI. Sensitivity, specificity, and negative
      and positive predictive values were 100%, 87%, 100%, and 29%, respectively, for
      the ability of MDCT angiography to detect reversible perfusion defects in the
      corresponding myocardial areas. CONCLUSION: MDCT angiography detected myocardial
      ischemia, as defined by reversible perfusion defects on MPI, with a positive
      predictive value of 29% in a nonselected study cohort. Compared with MPI alone,
      MDCT angiography added important morphologic information, but MPI remains
      mandatory for evaluating the functional relevance of coronary artery lesions.

PMID- 16085587
TI  - Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors
      after treatment with 90Y-DOTATOC.
AB  - Therapy with [(90)Y-DOTA(0), Tyr(3)]-octreotide (DOTATOC, where DOTA =
      tetraazacyclododecane tetraacetic acid and TOC = D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr
      Cys)-Thr(ol)) is established for the treatment of metastatic neuroendocrine
      tumors. Nevertheless, many patients experience disease relapse, and further
      treatment may cause renal failure. Trials with (177)Lu-labeled somatostatin
      analogs showed less nephrotoxicity. We initiated a prospective study with (177)Lu
      DOTATOC in patients with relapsed neuroendocrine tumors after (90)Y-DOTATOC
      treatment. METHODS: Twenty-seven patients, pretreated with (90)Y-DOTATOC, were
      included. The mean time between the last treatment with (90)Y-DOTATOC and (177)Lu
      DOTATOC was 15.4 +/- 7.8 mo (SD). All patients were injected with 7,400 MBq of
      (177)Lu-DOTATOC. Restaging was performed after 8-12 wk. Hematotoxicity or renal
      toxicity of World Health Organization grade 1 or 2 was not an exclusion
      criterion. RESULTS: Creatinine levels increased significantly, from 66 +/- 14
      micromol/L to 100 +/- 44 micromol/L (P < 0.0001), after (90)Y-DOTATOC therapy.
      The mean hemoglobin level dropped from 131 +/- 14 to 117 +/- 13 g/L (P < 0.0001)
      after (90)Y-DOTATOC therapy. (177)Lu-DOTATOC therapy was well tolerated. No
      serious adverse events occurred. The mean absorbed doses were 413 +/- 159 mGy for
      the whole body, 3.1 +/- 1.5 Gy for the kidneys, and 61 +/- 5 mGy for the red
      marrow. After restaging, we found a partial remission in 2 patients, a minor
      response in 5 patients, stable disease in 12 patients, and progressive disease in
      8 patients. Mean hemoglobin and creatinine levels did not change significantly.
      CONCLUSION: (177)Lu-DOTATOC therapy in patients with relapse after (90)Y-DOTATOC
      treatment is feasible, safe, and efficacious. No serious adverse events occurred.

PMID- 16085586
TI  - SPECT of serotonin transporters using 123I-ADAM: optimal imaging time after bolus
      injection and long-term test-retest in healthy volunteers.
AB  - (123)I-ADAM (2-([2-([dimethylamino]methyl)phenyl]thio)-5-(123)I-iodophenylamine)
      has been recently proposed as a new serotonin transporter (SERT) ligand for
      SPECT. The objective of this study was to characterize (123)I-ADAM in healthy
      volunteers. (123)I-ADAM distribution in the normal brain, pseudoequilibrium
      interval after a single injection, normal specific uptake values, and long-term
      test-retest variability and reliability were investigated. METHODS: Ten healthy
      volunteers underwent 2 SPECT sessions under the same conditions 47.6 +/- 24.0 d
      apart. Scans were sequentially acquired from the time of (123)I-ADAM intravenous
      injection up to 12 h after injection. Regions of interest (ROIs) for cerebellum
      (C), midbrain, thalamus, striatum, mesial temporal region, and cortex were drawn
      on MR images and pasted to corresponding SPECT slices after coregistration.
      Specific uptake ratios (SURs) at pseudoequilibrium and the simplified reference
      tissue model (SRTM) methods were used for quantification. SURs were obtained as
      ([region - C]/C) at each time point. Test-retest variability and reliability
      (intraclass correlation coefficient [ICC]) were calculated. RESULTS: The highest
      (123)I-ADAM specific uptake was found in the midbrain and thalamus, followed by
      the striatum and mesial temporal region. Quantification results using SUR and
      SRTM were correlated with R = 0.93 (test) and R = 0.94 (retest). SURs remained
      stable in all regions from 4 to 6 h after injection. Using SUR, test-retest
      variability/ICC were 13% +/- 11%/0.74 in midbrain, 16% +/- 13%/0.63 in thalamus,
      19% +/- 18%/0.62 in striatum, and 22% +/- 19%/0.05 in mesial temporal region.
      CONCLUSION: (123)I-ADAM accumulates in cerebral regions with high known SERT
      density. The optimal imaging time for (123)I-ADAM SPECT quantification is
      suggested to be from 4 to 6 h after a single injection. Long-term test-retest
      variability and reliability found in the midbrain are comparable to that reported
      with other (123)I-labeled SPECT ligands. These results support the use of (123)I
      ADAM SPECT for SERT imaging after a single injection in humans.

PMID- 16085588
TI  - The F + 0 protocol for diuretic renography results in fewer interrupted studies
      due to voiding than the F - 15 protocol.
AB  - Timing of diuretic administration is not universally standardized in renography.
      Over the past year, our practice has changed from F-15 administration of
      furosemide to an F + 0 protocol. Therefore, we have retrospectively compared
      these 2 cohorts to assess if the shorter interval between diuretic administration
      and study completion in the F + 0 study results in a greater frequency of
      patients able to complete the subsequent 30-min dynamic acquisition without
      disruption due to voiding. METHODS: We identified 108 diuretic (99m)Tc
      mercaptoacetyltriglycine renograms performed in the previous 18-mo period. Three
      patients were given furosemide at 30 min after the radiopharmaceutical and were
      excluded. Twenty studies in children under 3 y of age were excluded from
      consideration because voiding is neither restricted in this age group nor does
      voiding into a diaper cause disruption. Forty milligrams of furosemide were
      administered to adults, whereas 0.5 mg/kg was given to children. In the first
      cohort of 56 studies, radiopharmaceutical was administered 15 min after
      furosemide (F-15), whereas, in the second cohort of 29 patients, it was
      administered immediately thereafter (F + 0). In all cases, patients were asked to
      void proximal to radiopharmaceutical injection. Dynamic images and renogram
      curves were inspected for evidence of interruption or voiding midstudy.
      Statistical significance was determined by a 1-tailed Fisher exact test for
      proportions, with P < 0.05. RESULTS: The F-15 and F+0 groups of patients were
      comparable in terms of age, sex, and diuretic amount. In 17 of the F-15 patients,
      renography was interrupted because of voiding (30%), whereas this occurred in
      only 3 of the F + 0 patients (10%). This difference was significant at the P =
      0.033 level. The mean time of voiding was 18.3 min (range, 12-25 min) for F-15
      patients and 16 min (range, 12-19 min) for the F + 0 group. CONCLUSION: The F + 0
      renal diuretic protocol is associated with a significantly lower rate of
      disruption because of voiding than the F-15 protocol, likely due to the shorter
      period between diuretic administration and study termination, which results in
      less bladder distention and discomfort. On the basis of these data, the F + 0
      protocol appears to be a more tolerable procedure.

PMID- 16085589
TI  - Synchronous primary neoplasms detected on 18F-FDG PET in staging of patients with
      esophageal cancer.
AB  - Because of improvements in diagnostic technology, the incidental detection of
      synchronous primary tumors during the preoperative work-up of patients with
      esophageal cancer has increased. The aim of this study was to determine the rate
      and clinical relevance of synchronous neoplasms seen on (18)F-FDG PET in staging
      of esophageal cancer. METHODS: From January 1996 to July 2004, 366 patients with
      biopsy-proven malignancy of the esophagus underwent (18)F-FDG PET for initial
      staging. This series of patients was retrospectively reviewed for the detection
      of synchronous primary neoplasms. RESULTS: Twenty synchronous primary neoplasms
      (5.5%) were identified in 366 patients. Eleven neoplasms were in the colorectum,
      5 in the kidney, 2 in the thyroid gland, 1 in the lung, and 1 in the gingiva. One
      of the thyroid lesions and the lung lesion were erroneously interpreted as
      metastases, leading to incorrect upstaging of the esophageal tumor. CONCLUSION:
      (18)F-FDG PET detected unexpected synchronous primary neoplasms in 5.5% of
      patients with esophageal cancer. Sites of pathologic (18)F-FDG uptake should be
      confirmed by dedicated additional investigations before treatment, because
      synchronous neoplasms may mimic metastases.

PMID- 16085590
TI  - 188Re-HDD/lipiodol for treatment of hepatocellular carcinoma: a feasibility study
      in patients with advanced cirrhosis.
AB  - This study aimed to investigate the feasibility of the intraarterial
      administration of 3.7 GBq (188)Re-4-hexadecyl-1-2,9,9-tetramethyl-4,7-diaza-1,10
      decanethiol/lipiodol ((188)Re-HDD/lipiodol) for treatment of hepatocellular
      carcinoma (HCC) in patients with moderately advanced cirrhosis. METHODS: Patients
      with HCC and underlying cirrhosis classified as Child-Pugh B in terms of severity
      were eligible. Whole-body scintigraphies were performed at 4 time points after
      injection. Absorbed doses to the various organs were calculated according to the
      MIRD formalism. Urine was collected for 52 h after injection. Toxicity was
      assessed until 6 wk after administration by means of the Common Toxicity Criteria
      for Adverse Events (version 3.0) scale. Responses were evaluated on MRI and by
      alpha-fetoprotein (AFP) monitoring. RESULTS: A mean activity +/- SD of 3.7 +/-
      0.2 GBq (188)Re-HDD/lipiodol was administered in the hepatic artery to 12
      patients; 36.2% +/- 5.7% of the activity was excreted in the urine 52 h after
      injection. The absorbed dose to the liver, lungs, kidney, and thyroid was 7.6 +/-
      2.9, 4.8 +/- 2.6, 0.8 +/- 0.7, and 0.2 +/- 0.1 Gy (mean +/- SD), respectively.
      Two weeks after administration, 6 of 12 patients had adverse events consisting of
      aggravations of preexisting laboratory changes (3 patients), fatigue (2
      patients), vomiting (1 patient), fever (1 patient), encephalopathy (1 patient),
      and ascites (1 patient). Toxicity assessment at week 6 revealed single cases of
      the worsening of hyperbilirubinemia, pleural effusion, thrombocytopenia, and
      dyspnea. Three patients dropped out of the study because of deterioration of
      their general condition. The response was assessable by MRI in 8 patients: 1
      patient with a partial response and 7 patients with stable disease were reported.
      Nine patients with an initially elevated AFP were evaluated. Stable AFP was
      recorded in 1 patient and 3 showed a reduction, whereas a considerable increase
      was observed in 5 patients. CONCLUSION: After the administration of 3.7 GBq
      (188)Re-HDD/lipiodol, half of the Child-Pugh B patients in the present study had
      a worsening of their general condition or aggravation of preexisting symptoms.
      This was associated with a rise in AFP in a considerable number of patients. In
      the future, administration of the radiopharmaceutical as close to the tumor
      feeding arteries as possible might avoid further deterioration of the liver
      function and show enhanced antitumoral activity.

PMID- 16085591
TI  - Biodistribution and pharmacokinetics of the alphavbeta3-selective tracer 18F
      galacto-RGD in cancer patients.
AB  - (18)F-Galacto-RGD has been developed for PET of alpha(v)beta(3) integrin
      expression, a receptor involved in, for example, angiogenesis and metastasis. Our
      aim was to study the kinetics and biodistribution of (18)F-Galacto-RGD in cancer
      patients. METHODS: Nineteen patients with metastases of malignant melanoma (n =
      7), sarcomas (n = 10), or osseous metastases (n = 2) were examined. After
      injection of 133-200 MBq (18)F-Galacto-RGD, 3 consecutive emission scans from the
      pelvis to the thorax or dynamic emission scans of the tumor over 60 min, followed
      by 1 static emission scan of the body, were acquired. Time-activity curves and
      standardized uptake values (SUVs) were derived by image region-of-interest
      analysis with image-based arterial input functions. Compartmental modeling was
      used to derive the distribution volume for muscle tissue and tumors. RESULTS:
      (18)F-Galacto-RGD showed rapid blood clearance and primarily renal excretion.
      SUVs in tumors ranged from 1.2 to 9.0. Tumor-to-blood and tumor-to-muscle ratios
      increased over time, with peak ratios of 3.1 +/- 2.0 and 7.7 +/- 4.3,
      respectively, at 72 min. The tumor kinetics were consistent with a 2-tissue
      compartment model with reversible specific binding. Distribution volume values
      were, on average, 4 times higher for tumor tissue (1.5 +/- 0.8) than those for
      muscle tissue (0.4 +/- 0.1). The data suggest that there was only minimal free
      and bound (specific or nonspecific) tracer in muscle tissue. CONCLUSION: (18)F
      Galacto-RGD demonstrates a highly favorable biodistribution in humans with
      specific receptor binding. Most important, this study shows that (18)F-Galacto
      RGD allows visualization of alpha(v)beta(3) expression in tumors with high
      contrast. Consequently, this tracer offers a new strategy for noninvasive
      monitoring of molecular processes and may supply helpful information for planning
      and controlling of therapeutic approaches targeting the alpha(v)beta(3) integrin.

PMID- 16085592
TI  - Comparison of different methods for delineation of 18F-FDG PET-positive tissue
      for target volume definition in radiotherapy of patients with non-Small cell lung
      cancer.
AB  - PET with (18)F-FDG ((18)F-FDG PET) is increasingly used in the definition of
      target volumes for radiotherapy, especially in patients with non-small cell lung
      cancer (NSCLC). In this context, the delineation of tumor contours is crucial and
      is currently done by different methods. This investigation compared the gross
      tumor volumes (GTVs) resulting from 4 methods used for this purpose in a set of
      clinical cases. METHODS: Data on the primary tumors of 25 patients with NSCLC
      were analyzed. They had (18)F-FDG PET during initial tumor staging. Thereafter,
      additional PET of the thorax in treatment position was done, followed by planning
      CT. CT and PET images were coregistered, and the data were then transferred to
      the treatment planning system (PS). Sets of 4 GTVs were generated for each case
      by 4 methods: visually (GTV(vis)), applying a threshold of 40% of the maximum
      standardized uptake value (SUV(max); GTV(40)), and using an isocontour of SUV =
      2.5 around the tumor (GTV(2.5)). By phantom measurements we determined an
      algorithm, which rendered the best fit comparing PET with CT volumes using tumor
      and background intensities at the PS. Using this method as the fourth approach,
      GTV(bg) was defined. A subset of the tumors was clearly delimitable by CT. Here,
      a GTV(CT) was determined. RESULTS: We found substantial differences between the 4
      methods of up to 41% of the GTV(vis). The differences correlated with SUV(max),
      tumor homogeneity, and lesion size. The volumes increased significantly from
      GTV(40) (mean 53.6 mL) < GTV(bg) (94.7 mL) < GTV(vis) (157.7 mL) and GTV(2.5)
      (164.6 mL). In inhomogeneous lesions, GTV(40) led to visually inadequate tumor
      coverage in 3 of 8 patients, whereas GTV(bg) led to intermediate, more
      satisfactory volumes. In contrast to all other GTVs, GTV(40) did not correlate
      with the GTV(CT). CONCLUSION: The different techniques of tumor contour
      definition by (18)F-FDG PET in radiotherapy planning lead to substantially
      different volumes, especially in patients with inhomogeneous tumors. Here, the
      GTV(40) does not appear to be suitable for target volume delineation. More
      complex methods, such as system-specific contrast-oriented algorithms for contour
      definition, should be further evaluated with special respect to patient data.

PMID- 16085593
TI  - Regional mu-opioid receptor binding in insular cortex is decreased in bulimia
      nervosa and correlates inversely with fasting behavior.
AB  - The endogenous opioid system of the brain has been implicated in feeding
      behavior. Abnormal repeated activation of this system may constitute a neural
      substrate for the compulsive eating behavior observed in bulimia nervosa. This
      study examined the binding potential of the brain mu-opioid receptor (mu-OR) in
      bulimia nervosa. METHODS: Eight women with bulimia nervosa and 8 female controls
      underwent brain MRI followed by (11)C-carfentanil PET. Voxel-based methods were
      used to assess group differences in mu-OR binding between controls and bulimic
      subjects and to correlate mu-OR binding with the frequency of recent self
      reported abnormal eating behaviors in bulimic subjects. RESULTS: mu-OR binding in
      the left insular cortex was less in bulimic subjects than in controls and
      correlated negatively with recent fasting behavior. CONCLUSION: Changes in mu-OR
      binding in the insula may be important in the pathogenesis or maintenance of the
      self-perpetuating behavioral cycle of bulimic subjects because the insula is the
      primary gustatory cortex and has repeatedly been implicated in the processing of
      the reward value of food.

PMID- 16085594
TI  - Clinically significant incidental findings on the unenhanced CT portion of PET/CT
      studies: frequency in 250 patients.
AB  - PET/CT technology is in rapid evolution. It remains unclear if the unenhanced CT
      portion, performed for attenuation correction and lesion localization, provides
      additional independent diagnostic information not apparent on PET alone. The
      objective of the current study was to evaluate the incremental added value and
      frequency of potentially clinically significant incidental findings from the
      independent reading of the unenhanced CT portion of PET/CT studies by an expert
      CT radiologist. METHODS: PET/CT was performed on 250 patients (123 men and 127
      women; mean age, 56.5 y) referred for clinical evaluation of known or suspected
      cancer. Unenhanced CT studies were read without knowledge of findings from PET
      and PET/CT fused images. Findings from unenhanced CT were considered clinically
      significant if they were not detected or explained by PET findings and were
      considered, after examination of all available clinical data, to clearly require
      additional work-up. Small pulmonary nodules < 7 mm were not considered to require
      immediate work-up. RESULTS: Unenhanced CT revealed potentially clinically
      significant incidental findings in 7 patients. Three patients had indeterminate
      renal lesions, 1 patient had a solid renal mass, 1 patient had sclerotic bone
      metastases (albeit inactive on PET), 1 patient had liver cirrhosis with portal
      hypertension, and 1 patient had a 5 cm abdominal aortic aneurysm. These findings
      were generally not detected on PET. CONCLUSION: Clinically significant findings
      from the unenhanced CT portion of PET/CT are relatively infrequent (3%) but could
      be serious enough to warrant major alterations in clinical management. Thus, we
      believe it is most appropriate for the CT portion to be interpreted by a
      physician skilled in CT interpretation with special attention to the lesions that
      PET alone can fail to detect.

PMID- 16085595
TI  - Imaging of malignant bone involvement by morphologic, scintigraphic, and hybrid
      modalities.
AB  - Detection of bone involvement is essential for optimal therapy of oncologic
      patients. The purpose of imaging is to identify early bone involvement, to
      determine the full extent of the skeletal disease, to assess the presence of
      accompanying complications-such as fractures and cord compression-and to monitor
      response to therapy. Detection of bone involvement by various imaging modalities
      is based on either direct visualization of tumor infiltration or detection of the
      reaction of bone to the malignant process. MRI can identify early involvement of
      bone marrow. CT, which depends mainly on bone destruction, provides detailed bone
      morphology. In nuclear medicine, uptake of (18)F-FDG is directly into tumor
      cells, thus allowing for early detection and monitoring the response to therapy
      of tumor sites in the marrow, bone, and soft tissue, whereas increased uptake of
      (18)F-fluoride and (99m)Tc-methylene diphosphonate reflects the osteoblastic
      reaction of bone to the presence of tumor cells. The hybrid techniques SPECT/CT
      and PET/CT, recently introduced into clinical practice, provide a better anatomic
      localization of scintigraphic findings and may improve the diagnostic accuracy of
      SPECT and PET in detecting malignant bone involvement. The current review
      discusses the basis for the detection of malignant bone involvement by various
      morphologic and scintigraphic imaging modalities and the advantages and the
      limitations of each. Special emphasize is placed on the newer integrated
      technique of PET/CT. The role of imaging in identifying bone involvement in
      different malignant diseases is also discussed.

PMID- 16085596
TI  - Regional 11C-hydroxyephedrine retention in hibernating myocardium: chronic
      inhomogeneity of sympathetic innervation in the absence of infarction.
AB  - We have previously shown that ex vivo counting of (131)I-metaiodobenzylguanidine
      can identify regional reductions in sympathetic norepinephrine uptake in pigs
      with hibernating myocardium. However, nonneuronal uptake limited relative
      differences between regions and would preclude accurate assessment with
      conventional imaging. We therefore hypothesized that the superior specificity of
      the positron-emitting isotope (11)C-hydroxyephedrine (HED) would facilitate the
      imaging of regional differences, and we designed this study to determine whether
      altered uptake of norepinephrine by sympathetic nerves in viable, dysfunctional
      myocardium can be imaged in vivo and to determine the temporal progression and
      stability of sympathetic dysinnervation in hibernating myocardium. METHODS: Pigs
      (n = 15) were chronically instrumented with a 1.5-mm stenosis of the left
      anterior descending coronary artery, a procedure that we have previously shown to
      produce viable chronically dysfunctional myocardium with reduced resting flow, or
      hibernating myocardium, after 3 mo. Physiologic studies and HED PET were
      performed 1-5 mo later with the animals in the closed-chest sedated state. One
      animal with a myocardial infarct was analyzed separately. RESULTS: After 3 mo,
      anterior hypokinesis developed (wall thickening, 32% +/- 4% vs. 60% +/- 4%, P <
      0.001), with reductions in resting flow (subendocardial flow, 0.81 +/- 0.11 vs.
      1.20 +/- 0.18 mL/min/g, P < 0.05) and a critical reduction in subendocardial flow
      reserve (subendocardial adenosine flow, 0.53 +/- 0.20 vs. 3.96 +/- 0.43 mL/min/g,
      P < 0.001). Extensive defects in HED uptake were found for hibernating
      myocardium, with regional retention approximately 50% lower than that in normally
      perfused remote myocardium (0.035 +/- 0.002 vs. 0.066 +/- 0.002 min(-1), P <
      0.001). Relative HED uptake (left anterior descending coronary artery/remote) was
      lower in chronically instrumented animals than in control animals (n = 4, P <
      0.001) and animals studied 1 mo after instrumentation (n = 2, P < 0.05). The
      regional reduction in sympathetic nerve function was persistent and unaltered for
      at least 2 mo after the development of hibernating myocardium. CONCLUSION:
      Hibernating myocardium is associated with persistent reductions in regional
      uptake of norepinephrine by sympathetic nerves. The inhomogeneity in sympathetic
      innervation in viable dysfunctional myocardium is similar to that occurring after
      myocardial infarction and may contribute to arrhythmic death in patients with
      ischemic cardiomyopathy.

PMID- 16085597
TI  - Quantitative assessment of regional alveolar ventilation and gas volume using 13N
      N2 washout and PET.
AB  - Measurement of alveolar volume (Va) and regional ventilation (a) is crucial to
      understanding the pathophysiology of acute lung injury and ventilator-induced
      lung injury. PET has previously been used as a noninvasive, quantitative method
      to assess a, but formal validation of this technique in experimental lung injury
      is lacking. This study aims to validate Va and a regional assessment with PET,
      using inhaled (13)N-N(2) in pigs. METHODS: Two normal and 2 oleic acid-injured
      pigs were tracheotomized, mechanically ventilated, and studied in 5 different
      levels of ventilation by changing respiratory rate. In each experimental
      condition, lungs were washed-in and then washed-out with (13)N-N(2) through an
      open circuit in the ventilator. Using this method, multiframe images were
      acquired with a dedicated PET camera. Regions of interest (ROIs) were drawn on
      each lung. Regional time-activity curves during washout were generated for each
      ROI and fitted to a mono- and a bicompartmental model. Validation of this method
      was performed in 2 ways. First, regional values of predicted Va (Va(emission))
      were compared with regional volume obtained independently from density analysis
      on a transmission scan (Va(trans)). Second, regional values of predicted a were
      summed in each animal during each experimental condition and compared with minute
      ventilation values set on the ventilator. RESULTS: The bicompartmental model best
      fitted the experimental values in normal (94.7% [62.2%-100.0%] (median
      [interquartile range]) of the ROIs) as well as in injured animals (90.7% [81.6%
      97.4%] of the ROIs) (P = 0.49). Va(emission) significantly correlated with
      Va(trans) (R(2) = 0.89, P < 0.001) but exceeded Va(trans) by 10%. Finally, a
      strongly and positively correlated with minute-ventilation in both normal (R(2) =
      0.96, P < 0.001) and injured (R(2) = 0.96, P < 0.001) animals. CONCLUSION:
      Measurement of (13)N-N(2) washout using PET is accurate to assess regional
      alveolar volume and ventilation during experimental acute lung injury.

PMID- 16085598
TI  - Synthesis and evaluation of dopamine D3 receptor antagonist 11C-GR218231 as PET
      tracer for P-glycoprotein.
AB  - While searching for a PET method to determine the density and occupancy of the
      dopamine D(3) receptor, we found evidence that suggested that the dopamine D(3)
      antagonist GR218231 could be a substrate of the P-glycoprotein efflux pump. P
      glycoprotein protects the brain against toxic substances and xenobiotics, but it
      also hampers the delivery of various drugs into the brain. In this study, we
      aimed to explore whether radiolabeled GR218231 could be applied as a PET tracer
      for monitoring P-glycoprotein activity in the blood-brain barrier. Such an
      imaging technique could be useful for the development of new drugs and novel
      strategies to deliver drugs to the brain and for identification of undesirable
      drug-drug interactions. METHODS: As a potential PET tracer, GR218231 was labeled
      with (11)C by reaction of the newly synthesized desmethyl precursor with (11)C
      methyl triflate. The biodistribution of (11)C-GR218231 was determined in rats. To
      assess specific binding to the dopamine D(3) receptor, blocking experiments with
      unlabeled GR218231 (0.2 and 2.5 mg/kg) were performed. To demonstrate the
      influence of P-glycoprotein on cerebral uptake of (11)C-GR218231, the efflux pump
      was modulated with 50 mg/kg cyclosporine A. The sensitivity of (11)C-GR218231 for
      P-glycoprotein modulation was assessed in dose-response studies, using escalating
      cyclosporine A dosages. RESULTS: (11)C-GR218231 was prepared in 53% +/- 8% decay
      corrected radiochemical yield and had a specific activity of 15 +/- 10
      GBq/micromol (mean +/- SD). Biodistribution studies in rats revealed a low and
      homogeneous uptake in the brain. Pretreatment of the animals with unlabeled
      GR218231 did not demonstrate any specific binding. Modulation of P-glycoprotein
      with cyclosporine A caused a 12-fold higher (11)C-GR218231 uptake in the brain,
      indicating that the low cerebral tracer uptake was caused by the P-glycoprotein
      efflux pump in the blood-brain barrier. Cyclosporine A dose-escalation studies
      showed a dose-dependent sigmoidal increase in (11)C-GR218231 uptake in brain and
      spleen (median effective dose [ED(50)], 23.3 +/- 0.6 and 38.4 +/- 2.4 mg/kg,
      respectively), whereas a dose-dependent decrease was observed in the pancreas
      (ED(50), 36.0 +/- 4.4 mg/kg). CONCLUSION: Although (11)C-GR218231 is unsuited for
      dopamine D(3) receptor imaging with PET, it appears to be an attractive PET
      tracer for visualization and quantification of P-glycoprotein activity in the
      blood-brain barrier.

PMID- 16085599
TI  - Radiopharmaceutical chemistry of targeted radiotherapeutics, Part 2: radiolytic
      effects of 211At alpha-particles influence N-succinimidyl 3-211AT-astatobenzoate
      synthesis.
AB  - A variety of promising targeted radiotherapeutics labeled with alpha-emitters
      have been developed. Clinical investigation of these radiopharmaceuticals
      requires the production of high activity levels, which can be hindered by alpha
      particle-mediated radiolytic effects on labeling chemistry. The purpose of this
      study was to investigate the effects of radiation dose on the synthesis of N
      succinimidyl 3-(211)At-astatobenzoate (SAB), a compound used in our clinical
      trials for labeling antibodies with alpha-particle-emitting (211)At. METHODS:
      Yields for the synthesis of SAB as a function of the radiation dose received by
      the reaction medium were determined. The variables studied included the
      radiohalogenation precursors N-succinimidyl 3-(tri-n-butylstannyl)benzoate
      (BuSTB) and N-succinimidyl 3-(trimethylstannyl)benzoate (MeSTB); the solvents
      chloroform, benzene, and methanol; and the addition of acetic acid and the
      oxidant N-chlorosuccinimide. The (211)At product spectra were determined from
      high-performance liquid chromatograms and then plotted against radiation dose.
      RESULTS: SAB production declined rapidly with increasing dose, consistent with
      the documented radiolytic decomposition of BuSTB and MeSTB in chloroform. Even
      though these tin precursors were not appreciably degraded in benzene, SAB could
      not be produced in this solvent; instead, highly lipophilic (211)At-labeled
      species were generated in nearly quantitative yields. Although a dose-dependent
      decline in SAB yield also was observed in methanol, both in the presence and in
      the absence of an oxidant, the results were better than those obtained with the
      other solvents. An unexpected observation was that SAB could be obtained at a
      yield of greater than 30% when the reaction was run in methanol without the
      addition of acetic acid or an oxidant; these 2 components previously were
      considered essential for astatodestannylation. CONCLUSION: Radiolytic factors can
      play an important role in the synthesis of clinical-level activities of (211)At
      labeled radiopharmaceuticals, necessitating the development of reaction
      conditions different from those that are used successfully at lower activity
      levels.

PMID- 16085601
TI  - Advantage of 188Re-radiopharmaceuticals in hepatocellular cancer and liver
      metastases.

PMID- 16085600
TI  - Blood-based red marrow dosimetry: where's the beef?

PMID- 16085602
TI  - Radioiodine therapy and pregnancy.

PMID- 16085603
TI  - Are validated questionnaires valid?

PMID- 16085604
TI  - Clinical outcome at a minimum of five years after reconstruction of the anterior
      cruciate ligament.
AB  - BACKGROUND: We are not aware of any previous studies in which independent
      measurements of function with validated outcome questionnaires such as the Knee
      Injury and Osteoarthritis Outcome Score and the International Knee Documentation
      Committee score were evaluated five years after reconstruction of the anterior
      cruciate ligament. We hypothesized that patient demographics, mechanism of
      injury, and intra-articular injuries and their treatment are factors associated
      with function five years after reconstruction of the anterior cruciate ligament.
      METHODS: A consecutive series of unilateral, arthroscopically assisted primary
      reconstructions of the anterior cruciate ligament performed by one surgeon using
      a patellar tendon graft was evaluated. Data on patient demographics, injury
      variables, and intra-articular lesions noted at the time of surgery were
      collected prospectively. Multivariable regression analysis was used to identify
      independent predictors of outcomes as measured with five questionnaires. RESULTS:
      Sixty-nine percent (217) of 314 knees with a reconstruction of the anterior
      cruciate ligament were followed for an average of 5.4 years. The average age at
      the time of the operation was twenty-seven years. Independent predictors of a
      worse outcome, which was measured with the overall Knee Injury and Osteoarthritis
      Outcome Score, the International Knee Documentation Committee score, the Lysholm
      score, and the Western Ontario and McMaster Universities Osteoarthritis Index
      score, included the patient's recollection of hearing or feeling a pop at the
      time of the injury, a weight gain of >15 lb (6.8 kg), and no change in
      educational level since the surgery. There was a lack of association between the
      outcome and either the occurrence or the form of treatment of a meniscal tear or
      chondromalacia of the articular cartilage. CONCLUSIONS: To our knowledge, we
      performed the first prospective cohort study to evaluate the prognosis following
      reconstruction of the anterior cruciate ligament by identifying significant
      associations between multiple variables and clinical outcomes as measured with
      validated questionnaires. The clinician can counsel patients about the
      intermediate-term functional outcomes of reconstructions of the anterior cruciate
      ligament on the basis of these findings. Suggestions regarding weight control and
      future education may improve intermediate-term outcomes.

PMID- 16085605
TI  - Comparison of internal fixation with total hip replacement for displaced femoral
      neck fractures. Randomized, controlled trial performed at four years.
AB  - BACKGROUND: Recent randomized, controlled trials performed at two years
      postoperatively have shown that a primary total hip replacement is superior to
      internal fixation for the treatment of a displaced femoral neck fracture in a
      relatively healthy, mentally competent, elderly patient. The primary aim of the
      present study was to evaluate the outcomes at four years. METHODS: One hundred
      and two patients (mean age, eighty years) who had an acute displaced femoral neck
      fracture were randomly allocated to be treated with total hip replacement or
      internal fixation. The inclusion criteria were an age of at least seventy years,
      absence of severe cognitive dysfunction, an independent living status, and the
      ability to walk independently. The main outcome measurements were hip
      complications, reoperations, hip function, and health-related quality of life.
      RESULTS: The mortality rate was 25% in both groups. At the forty-eight-month
      follow-up evaluation, the rate of hip complications was 4% in the patients
      treated with total hip replacement and 42% in those treated with internal
      fixation (p < 0.001) and the reoperation rates were 4% and 47%, respectively (p <
      0.001). The arthroplasty group had no additional hip complications or
      reoperations between the twenty-four and forty-eight-month follow-up visits. In
      the fixation group, the percentage of hip complications increased from 36% to 42%
      and the percentage of reoperations increased from 42% to 47% during the same
      period. The hip function was significantly better and the decline in health
      related quality of life was less pronounced in the arthroplasty group than it was
      in the fixation group at the four, twelve, and twenty-four-month follow-up
      evaluations. Ninety-seven percent of the patients in the arthroplasty group and
      57% of the patients in the fixation group who were available for follow-up at
      forty-eight months had no hip complications (p < 0.001). CONCLUSIONS: Compared
      with internal fixation, primary total hip replacement provides a better outcome
      for mentally competent elderly patients with a displaced femoral neck fracture.
      The complication and reoperation rates were significantly lower and hip function
      and health-related quality of life were at least as good at four years after the
      surgery.

PMID- 16085606
TI  - Accuracy of the Sauvegrain method in determining skeletal age during puberty.
AB  - BACKGROUND: The method of Sauvegrain et al. for the assessment of skeletal age
      from radiographs of the elbow is useful during the two years of the pubertal
      growth spurt. The purpose of this study was to determine the accuracy of the
      method and its value in pediatric orthopaedics. METHODS: The Sauvegrain method
      uses four anatomical landmarks of the elbow: the lateral condyle, trochlea,
      olecranon apophysis, and proximal radial epiphysis. It is based on a 27-point
      scoring system. The scores for these structures are summed, and a total score is
      determined. A graph is then used to determine the skeletal age. The method was
      evaluated by three independent observers who used it to assess skeletal age on
      anteroposterior and lateral radiographs of the left elbow of sixty boys and sixty
      girls and compared the results with assessments made with use of the Greulich and
      Pyle atlas on posteroanterior radiographs of the left hand and wrist. Skeletal
      age determinations were performed twice by each observer at a four-week interval.
      RESULTS: The skeletal age determination from radiographs of the elbow was more
      precise because a clear semiannual age determination was possible. On the basis
      of the rating by the observers, the Sauvegrain method presented excellent
      interobserver correlation (r = 0.93) and excellent reproducibility (r = 0.96).
      The correlation between the methods of Sauvegrain et al. and Greulich and Pyle
      was good (r = 0.85). Nevertheless, certain elbow growth centers showed an
      intermediate developmental morphology, which failed to correspond to the score
      described by Sauvegrain et al. This led to errors in the interpretation of data.
      We suggest an intermediate score for these cases, and we modified the original
      graph to make it more accurate. CONCLUSIONS: The modified method of Sauvegrain et
      al. is simple, reliable, and reproducible, and it complements the Greulich and
      Pyle atlas. In clinical practice, maturity can best be evaluated by associating
      skeletal age, annual growth rate, and secondary sexual characteristics.
      Therefore, this method is useful when major decisions such as the timing of
      epiphysiodesis or spinal arthrodesis are necessary during puberty.

PMID- 16085607
TI  - The Reverse Shoulder Prosthesis for glenohumeral arthritis associated with severe
      rotator cuff deficiency. A minimum two-year follow-up study of sixty patients.
AB  - BACKGROUND: Patients who have pain and dysfunction from glenohumeral arthritis
      associated with severe rotator cuff deficiency have few treatment options. The
      goal of this study was to retrospectively evaluate the short-term results of
      arthroplasty with use of the Reverse Shoulder Prosthesis in the management of
      this problem. METHODS: We report the results for sixty patients (sixty shoulders)
      with a rotator cuff deficiency and glenohumeral arthritis who were followed for a
      minimum of two years. Thirty-five patients had no previous shoulder surgery,
      whereas twenty-three had had either an open or arthroscopic rotator cuff repair,
      one had had a subacromial decompression, and one had had a biceps tendon repair.
      All patients were assessed preoperatively and postoperatively with the American
      Shoulder and Elbow Surgeons scoring system for pain and function and with visual
      analog scales for pain and function. They were also asked to rate their
      satisfaction with the outcome. The shoulder range of motion was measured
      preoperatively and postoperatively. RESULTS: The average age of the patients was
      seventy-one years. The average duration of follow-up was thirty-three months. All
      measures improved significantly (p < 0.0001). The mean total score on the
      American Shoulder and Elbow Surgeons system improved from 34.3 to 68.2; the mean
      function score, from 16.1 to 29.4; and the mean pain score, from 18.2 to 38.7.
      The score for function on the visual analog scale improved from 2.7 to 6.0, and
      the score for pain on the visual analog scale improved from 6.3 to 2.2. Forward
      flexion increased from 55.0 degrees to 105.1 degrees, and abduction increased
      from 41.4 degrees to 101.8 degrees. Forty-one of the sixty patients rated the
      outcome as good or excellent; sixteen were satisfied, and three were
      dissatisfied. There were a total of thirteen complications in ten patients (17%).
      Seven patients (12%) had eight failures, requiring revision surgery to another
      Reverse Shoulder Prosthesis in five patients (one shoulder had two revisions) and
      revision to a hemiarthroplasty in two patients because of deep infection.
      CONCLUSIONS: The data from this study suggest that arthroplasty with the Reverse
      Shoulder Prosthesis may be a viable treatment for patients with glenohumeral
      arthritis and a massive rotator cuff tear. However, future studies will be
      necessary to determine the longevity of the implant and whether it will provide
      continued improvement in function.

PMID- 16085608
TI  - UniSpacer arthroplasty of the knee.
AB  - BACKGROUND: The operative treatment of medial compartment knee arthritis is
      controversial. The purpose of the present study was to report the experience of a
      single surgeon with the UniSpacer arthroplasty for the treatment of isolated
      medial compartment arthritis of the knee. METHODS: From April 2002 through
      November 2002, thirty-seven UniSpacer arthroplasties were performed in thirty
      four patients for the treatment of arthritis that primarily involved the medial
      compartment of the knee. The Ahlback radiographic evaluation scale was used to
      grade the severity of arthritis; the mean preoperative score was 2.6 points for
      the medial compartment and 0.5 point for both the lateral and patellofemoral
      compartments. The study group included eighteen women (nineteen knees) and
      sixteen men (eighteen knees) who had a mean age of fifty-five years (range, forty
      two to seventy-five years) at the time of surgery. Twelve patients had had a
      previous arthroscopic meniscectomy. The mean preoperative Knee Society function
      score was 60 points (range, 40 to 80 points), and the mean preoperative Knee
      Society objective score was 62 points (range, 40 to 76 points). RESULTS: After a
      mean duration of follow-up of twenty-six months (range, twenty-four to twenty
      nine months), there were no excellent, ten good, fifteen fair, and twelve poor
      results. The mean postoperative total function score was 69 points (range, 40 to
      82 points), and the mean Knee Society objective score was 72 points (range, 45 to
      88 points). Six of the twelve poor results were in knees that had dislocation of
      the UniSpacer. All twelve knees were revised to a total knee arthroplasty.
      CONCLUSIONS: On the basis of this experience, we do not recommend UniSpacer
      arthroplasty for the treatment of degenerative arthritis of the medial
      compartment of the knee.

PMID- 16085609
TI  - The impact of diabetes on patient outcomes after ankle fracture.
AB  - BACKGROUND: Ankle fracture is one of the most common injuries treated by
      orthopaedic surgeons, and the presence of diabetes complicates treatment and
      recovery from this injury. Although a higher prevalence of adverse postoperative
      events has been found in small series of diabetic patients with an ankle
      fracture, we are not aware of any large national series with specific
      documentation of the outcomes following ankle fracture in patients with diabetes.
      METHODS: We analyzed data from the Nationwide Inpatient Sample database for the
      years 1988 through 2000. Information regarding the hospitalizations of 160,598
      adult patients with an ankle fracture who underwent subsequent surgical
      procedures was extracted from the database. Multiple linear and logistic
      regression models were used to ascertain whether patients with diabetes mellitus
      were more likely than patients without diabetes mellitus to die while in the
      hospital, to have in-hospital postoperative complications, to stay longer in the
      hospital, to have a higher incidence of non-routine discharge, and to have a
      higher total cost associated with the hospital stay. RESULTS: Significant
      increases in in-hospital mortality, the rate of in-hospital postoperative
      complications, the length of hospital stay, the rate of non-routine discharge,
      and the total charges were found in the diabetic patient group (p < 0.001).
      Specifically, we found that diabetic patients across all levels of fracture
      severity (closed unimalleolar, closed bimalleolar or trimalleolar, and dislocated
      or open fractures) stayed in the hospital for about one additional day (mean, 4.7
      compared with 3.6 days) and incurred more than dollar 2000 in increased charges
      (mean, dollar 12,898 compared with dollar 10,794). CONCLUSIONS: This nationally
      representative study of inpatients in the United States provides evidence that
      diabetic patients with an operatively treated ankle fracture are likely to have
      worse results than non-diabetic patients with regard to postoperative
      complications, mortality, rate of non-routine discharge, length of hospital stay,
      and total hospital charges.

PMID- 16085610
TI  - The functional outcomes of total knee arthroplasty.
AB  - BACKGROUND: As an elective procedure, total knee arthroplasty is under scrutiny
      to evaluate its cost-effectiveness. In this review, we examined the available
      literature on total knee arthroplasty to assess the evidence regarding factors
      associated with better functional outcomes. METHODS: A structured literature
      search of English-language databases was performed to identify studies of the
      functional outcomes of total knee arthroplasty that had been published between
      1995 and April 2003. Inclusion criteria were a study of primary total knee
      arthroplasty, more than 100 knees in the study, provision of baseline data and
      rating of postoperative outcomes with a standardized symptom scale, and an
      experimental or quasi-experimental study design. The abstracting form included a
      list of potential prognostic factors, including comorbidities, radiographic
      evidence of joint destruction, bone loss, integrity of the extensor mechanism,
      range of motion, alignment, tibiofemoral angle, and ligament integrity, as well
      as the characteristics of the operating surgeon, such as procedure volume and
      experience. RESULTS: Sixty-two studies met the criteria and were reviewed. Total
      knee arthroplasty was found to be associated with substantial functional
      improvement, with the effect sizes varying with the measure that was used.
      Physician-derived measures showed effect sizes of 2.35 and 3.91, whereas patient
      derived measures showed smaller effect sizes (1.27 and 1.62). Few investigators
      used multivariate models to identify associations between outcomes and patient
      characteristics. CONCLUSIONS: Total knee arthroplasty is a generally effective
      procedure, but the current English-language literature does not support specific
      recommendations about which patients are most likely to benefit from it.

PMID- 16085611
TI  - Pain dominates measurements of elbow function and health status.
AB  - BACKGROUND: Elbow function can be quantified with use of physician-based elbow
      rating systems and health status questionnaires. Our hypothesis was that pain has
      a strong influence on these scores, which overwhelms the influence of objective
      factors such as motion. METHODS: One hundred and four patients were evaluated, at
      a minimum of six months (average, forty-six months) after the latest surgery for
      an intra-articular fracture of the elbow, with use of three physician-based
      evaluation instruments (Mayo Elbow Performance Index [MEPI], Broberg and Morrey
      rating system, and American Shoulder and Elbow Surgeons Elbow Evaluation
      Instrument [ASES]), an upper-extremity-specific health status questionnaire
      (Disabilities of the Arm, Shoulder and Hand [DASH]), and a general health status
      questionnaire (Short Form-36 [SF-36]). Multivariate analysis of variance and
      regression modeling were used to identify the factors that account for the
      variability in scores derived with these measures-in other words, which factors
      have the strongest influence on the final score. RESULTS: Pain alone accounted
      for 66% of the variability in the MEPI scores, 59% of the variability in the
      Broberg and Morrey scores, and 57% of the variability in the ASES scores. Models
      that included other factors accounted for only slightly more variability (73%,
      79%, and 79%, respectively), and those that did not include pain accounted for
      only 22%, 41%, and 41% of the variability. Thirty-six percent of the variability
      in the DASH scores could be accounted for by pain alone, and 45% could be
      accounted for by pain and range of motion. Models not including pain accounted
      for only 17% of the variability in the DASH scores. CONCLUSIONS: Pain has a very
      strong influence on both physician-rated and patient-rated quantitative measures
      of elbow function. Consequently, these measures may be strongly influenced by the
      psychosocial aspects of illness that have a strong relationship with pain, and
      objective measures of elbow function such as mobility may be undervalued. It may
      be advisable to evaluate pain separately from objective measures of elbow
      function in physician-based elbow ratings.

PMID- 16085612
TI  - Cervicothoracic extension osteotomy for chin-on-chest deformity in ankylosing
      spondylitis.
AB  - BACKGROUND: Chin-on-chest deformity is a disabling manifestation of ankylosing
      spondylitis. Surgical treatment consists of extension osteotomy at the
      cervicothoracic junction. The purpose of this study was to characterize the
      clinical presentation of this deformity and to determine the long-term functional
      and radiographic outcomes of treatment. METHODS: The medical records and
      radiographs of all twenty-six patients treated with cervicothoracic extension
      osteotomy by one of us between 1976 and 2001 were retrospectively reviewed. Three
      patients died during the two-year-minimum follow-up period. The remaining twenty
      three patients were followed for an average of 4.5 years (range, two years to
      twenty-one years and ten months). RESULTS: The mean sagittal correction was 38
      degrees. Delayed union in two patients and additional cervical trauma in two
      others resulted in partial loss of the initial correction. Quadriplegia developed
      in one patient, who died as a result of subluxation at the osteotomy site. Five
      patients had irritation of the eighth cervical nerve root postoperatively.
      CONCLUSIONS: Extension osteotomy can reliably improve sagittal alignment and
      horizontal gaze as well as decrease neck pain, eating difficulties, and
      neurologic abnormalities. Internal fixation is recommended to prevent
      subluxation, delayed union, nonunion, loss of correction, or neurologic injury.
      There is a risk of death or catastrophic neurologic injury from the procedure.

PMID- 16085613
TI  - Subscapularis muscle function and structure after total shoulder replacement with
      lesser tuberosity osteotomy and repair.
AB  - BACKGROUND: Recent studies have suggested that tenotomy and repair of the
      subscapularis tendon carried out for anterior approaches to the shoulder can be
      followed by failure of the tendon repair and by changes resulting in permanent
      loss of subscapularis function. We hypothesized that release of the subscapularis
      with use of a superficial osteotomy of the lesser tuberosity followed by repair
      of the two opposing bone surfaces would lead to consistent bone-to-bone healing,
      which would be possible to monitor radiographically, and would lead to
      satisfactory clinical and structural outcomes. METHODS: Thirty-nine shoulders in
      thirty-six consecutive patients who, at an average age of fifty-seven years, had
      undergone total shoulder replacement through an anterior approach involving an
      osteotomy of the lesser tuberosity were evaluated at an average of thirty-nine
      months. Assessment included a standardized interview and physical examination,
      scoring according to the system described by Constant and Murley, and imaging
      with conventional radiography and computed tomography to assess healing of the
      osteotomy site and changes in the subscapularis. RESULTS: The osteotomized
      tuberosity fragment healed in an anatomical position in all shoulders, and no
      cuff tendon ruptures were observed. At the time of follow-up, thirty-three (89%)
      of thirty-seven shoulders evaluated with a belly-press test had a negative result
      and twenty-seven (75%) of thirty-six shoulders evaluated with a lift-off test had
      an unequivocally normal result. Fatty infiltration of the subscapularis muscle
      increased after the operation (p < 0.0001) and was at least stage two in eleven
      (32%) of thirty-four shoulders. The fatty infiltration had progressed by one
      stage in eight (24%) of the thirty-four shoulders, by two stages in five
      shoulders (15%), and by three stages in two shoulders (6%). CONCLUSIONS:
      Osteotomy of the lesser tuberosity provides an easy anterior approach for total
      shoulder replacement and is followed by consistent bone-to-bone healing, which
      can be monitored, and good subscapularis function. In the presence of documented
      anatomical healing of the osteotomy site, postoperative fatty infiltration of the
      subscapularis muscle remains unexplained and needs to be investigated further as
      it is associated with a poorer clinical outcome.

PMID- 16085614
TI  - The impact of infection after total hip arthroplasty on hospital and surgeon
      resource utilization.
AB  - BACKGROUND: Deep infection following total hip arthroplasty is a devastating
      complication for the patient and a costly one for patients, surgeons, hospitals,
      and payers. The purpose of this study was to compare revision total hip
      arthroplasty for infection, revision total hip arthroplasty for aseptic
      loosening, and primary total hip arthroplasty with respect to their impact on
      hospital and surgeon resource utilization and referral patterns to a tertiary
      care hospital. METHODS: Clinical, demographic, and economic data were obtained
      for twenty-five consecutive patients with an infection after a total hip
      replacement who underwent a two-stage revision arthroplasty (Group 1) performed
      by one of two surgeons, between March 2001 and December 2002, at a single
      institution. Similar data were collected during the same time-period for a cohort
      of twenty-five consecutive patients who underwent revision of both components
      because of aseptic loosening (Group 2) and twenty-five consecutive patients who
      underwent a primary hip arthroplasty (Group 3). Quantitative and categorical
      variables were compared among the groups. Referral patterns were examined by
      reviewing the primary diagnosis for all patients referred to our institution for
      a revision total hip arthroplasty during a five-year period. RESULTS: Revision
      procedures for infection were associated with longer operative time, more blood
      loss, and a higher number of complications compared with revisions for aseptic
      loosening or primary total hip arthroplasty (p < 0.02 for all). Revisions for
      infection were also associated with a higher total number of hospitalizations,
      total number of days in the hospital, total number of operations, total hospital
      costs, total outpatient visits, and total outpatient charges during the twelve
      month period following the index procedure (p < 0.001 for all). The incidence of
      referrals to our institution for a diagnosis of infection following total hip
      arthroplasty increased significantly over a five-year period (Spearman rank
      correlation, 1.0; p = 0.0083), while referral rates for revision for causes other
      than infection remained relatively constant (Spearman rank correlation, 0.500; p
      = 0.3910). CONCLUSIONS: The treatment of patients with an infection after a total
      hip arthroplasty is associated with significantly greater hospital and physician
      resource utilization compared with the treatment of patients who have a revision
      because of aseptic loosening or who have a primary total hip arthroplasty. We
      believe that the lack of incremental reimbursement associated with these
      procedures results in strong financial disincentives for physicians and hospitals
      to provide treatment for patients with an infection after a total hip
      arthroplasty.

PMID- 16085615
TI  - Arthroscopic osseous Bankart repair for chronic recurrent traumatic anterior
      glenohumeral instability.
AB  - BACKGROUND: A chronic osseous Bankart lesion has traditionally been treated with
      soft-tissue repair and/or open bone-grafting for a large glenoid defect. We
      developed an arthroscopic method of osseous reconstruction of the glenoid without
      bone-grafting. The purpose of this study was to evaluate the postoperative
      outcomes of our technique for chronic recurrent traumatic anterior glenohumeral
      instability. METHODS: A consecutive series of forty-two shoulders in forty-one
      patients with chronic recurrent traumatic glenohumeral instability underwent an
      arthroscopic osseous Bankart repair. All shoulders were evaluated preoperatively
      with three-dimensionally reconstructed computed tomography, which confirmed an
      osseous fragment at the anteroinferior portion of the glenoid. The average bone
      loss in the glenoid was 24.8% (range, 11.4% to 38.6%), and the average fragment
      size was 9.2% (range, 2.1% to 20.9%) of the glenoid fossa. In all shoulders, a
      displaced osseous fragment, firmly attached to the labroligamentous complex, was
      separated from the glenoid neck before reduction and fixation in the optimal
      position with use of suture anchors. All patients were assessed with use of the
      scoring systems of Rowe et al. and the University of California at Los Angeles
      preoperatively and at the final evaluation. RESULTS: The mean duration of follow
      up was thirty-four months. At that time, thirty-nine of the forty-two shoulders
      were rated as having a good or excellent result. The mean Rowe score improved
      from 33.6 points preoperatively to 94.3 points postoperatively (p < 0.01). The
      mean score on the University of California at Los Angeles system improved from
      20.5 points preoperatively to 33.6 points at the final evaluation (p < 0.01). The
      average passive external rotation was 75 degrees with the arm at the side and 93
      degrees with the arm at 90 degrees of abduction. Two patients had a reinjury.
      Eventually, thirty-five of thirty-seven patients who were active participants in
      sports returned to the sport they had played before the injury. CONCLUSIONS:
      Arthroscopic osseous Bankart repair with use of suture anchors yields a
      successful outcome even in shoulders with a chronic large glenoid defect.

PMID- 16085616
TI  - Operative treatment of tibial fractures in children: are elastic stable
      intramedullary nails an improvement over external fixation?
AB  - BACKGROUND: Operative treatment of tibial fractures in children requires implants
      that do not violate open physes while maintaining tibial length and alignment.
      Both elastic stable intramedullary nails and external fixation can be utilized.
      We retrospectively reviewed our experience with these two techniques to determine
      if one is superior to the other. METHODS: We retrospectively reviewed the
      operative records and trauma registries of three institutions within our hospital
      system and identified thirty-five consecutive patients with open physes who had
      undergone operative treatment of a tibial fracture between April 1997 and June
      2004. Four patients were excluded because they had been managed with locked
      intramedullary nails or with pins and plaster. Of the thirty-one remaining
      patients, sixteen had been managed with elastic stable intramedullary nails and
      fifteen had been managed with unilateral external fixation. The clinical and
      radiographic outcomes were compared. The functional outcomes were compared with
      use of the Pediatric Outcomes Data Collection Instrument. Complications related
      to treatment, such as malunion, delayed union, nonunion, infection, and the need
      for subsequent surgical treatment also were compared. RESULTS: Thirty-one
      patients with thirty-one operatively treated tibial fractures were available for
      evaluation. Fifteen patients had been managed with external fixation. Seven of
      these patients had a closed fracture, and eight had an open fracture. There were
      seven healing complications in this group, including two delayed unions, three
      nonunions, and two malunions. Sixteen patients had been managed with elastic
      stable intramedullary nailing. Eleven patients had a closed fracture, and five
      had an open fracture. The mean time to union for the intramedullary nailing group
      (seven weeks) was significantly shorter than that for the external fixation group
      (eighteen weeks) (p < 0.01). The functional outcomes for the intramedullary
      nailing group were significantly better than those for the external fixation
      group in the categories of pain, happiness, sports, and global function (the mean
      of the mean scores of the first four categories) (p < 0.01 for these
      comparisons). CONCLUSIONS: When surgical stabilization of tibial fractures in
      children is indicated, we believe that the preferred method of fixation is with
      elastic stable intramedullary nailing.

PMID- 16085617
TI  - Comparison of polyethylene wear associated with cobalt-chromium and zirconia
      heads after total hip replacement. A prospective, randomized study.
AB  - BACKGROUND: A ceramic femoral head is an alternative to a metal femoral head for
      the bearing surface of total hip arthroplasty. The purpose of this study was to
      compare polyethylene wear in patients who had undergone bilateral total hip
      arthroplasty with implants that differed only with regard to the material used
      for the femoral head: a zirconia head was used on one side, and a cobalt-chromium
      head was inserted on the contralateral side. METHODS: A prospective, randomized
      study was performed to evaluate the outcomes in fifty-two patients who had
      undergone sequential bilateral primary total hip replacement. A zirconia head was
      used in one hip, and a cobalt-chromium head was used in the other. There were
      forty-eight men and four women; the mean age at the time of surgery was 44.2
      years. The mean duration of follow-up was 7.1 years. Clinical and radiographic
      evaluations were performed preoperatively and at six weeks; three, six, and
      twelve months; and yearly postoperatively. Linear wear of the polyethylene liner
      was measured radiographically. Two femoral components with a zirconia head had
      aseptic loosening and were revised. The explanted heads were evaluated with use
      of interferometry, environmental scanning electron microscopy, and x-ray
      diffraction studies. RESULTS: The mean polyethylene wear rate was 0.08 mm/yr in
      association with the zirconia heads and 0.17 mm/yr in association with the cobalt
      chromium heads (p = 0.004). The mean amount of volumetric polyethylene wear was
      350.8 mm3 in association with the zirconia heads and 744.7 mm3 in association
      with the cobalt-chromium heads (p = 0.004). With regard to surface roughness, the
      Ra values of the two explanted zirconia heads were 15.87 and 17.35 nm and the Rpm
      values were 153.86 and 156.18 nm. Two identical zirconia heads that had not been
      implanted had Ra values of 5.31 and 5.48 nm and Rpm values of 65.27 and 66.35 nm.
      Four unimplanted cobalt-chromium heads that were identical to the ones implanted
      in this study had Ra values ranging between 25 and 50 nm and Rpm values ranging
      between 262.6 and 525.2 nm. Little phase transformation was noted in the two
      revised zirconia heads. CONCLUSIONS: The mean amount and rate of polyethylene
      wear were significantly lower in the hips with a zirconia head than they were in
      the hips with a cobalt-chromium head, presumably because the zirconia heads had a
      smoother articulating surface.

PMID- 16085618
TI  - Proximal femoral replacement for the treatment of periprosthetic fractures.
AB  - BACKGROUND: A periprosthetic fracture around the femoral component is a rare but
      potentially problematic complication after total hip arthroplasty. Reconstruction
      can be challenging, especially when severe bone stock deficiency is encountered.
      Proximal femoral replacement is one method of treating the severely deficient
      proximal part of the femur. The present report describes the outcomes of revision
      total hip arthroplasty with use of a proximal femoral replacement in a cohort of
      patients who had a Vancouver type-B3 periprosthetic fracture. METHODS: With use
      of a computerized institutional database, all patients in whom a Vancouver type
      B3 fracture (characterized by severe proximal bone deficiency and a loose femoral
      stem) had been treated with a proximal femoral replacement were identified. A
      modular femoral replacement with proximal porous coating had been used in all
      cases. The twenty-one patients who were identified had had a mean age of 78.3
      years (range, fifty-two to ninety years) at the time of the index operation. The
      clinical and radiographic records of these patients were reviewed. RESULTS: At
      the time of the latest follow-up (mean, 3.2 years), all but one of the patients
      were able to walk and had minimal to no pain. Complications included persistent
      wound drainage that was treated with incision and drainage (two hips),
      dislocation (two hips), refracture of the femur distal to the stem (one hip), and
      acetabular cage failure (one hip). CONCLUSIONS: Despite a relatively high
      complication rate, we believe that proximal femoral replacement is a viable
      option for the treatment of periprosthetic fractures in older patients with
      severe bone deficiency. If a proximal femoral replacement is used, the stability
      of the hip must be tested diligently intraoperatively and a constrained
      acetabular liner should be utilized if instability is encountered. In order to
      enhance the bone stock, the proximal part of the femur, however poor in quality,
      should be retained for reapproximation onto the implant.

PMID- 16085619
TI  - Rotator cuff repair in patients with rheumatoid arthritis.
AB  - BACKGROUND: Currently, there is very little information available regarding the
      results of rotator cuff repair in patients with rheumatoid arthritis. Therefore,
      we reviewed our experience to determine the results, the risk factors for an
      unsatisfactory outcome, and the rates of failure of this procedure. METHODS: We
      retrospectively reviewed the records of all patients with rheumatoid arthritis
      who had undergone repair of a rotator cuff tear at our institution from 1988 to
      2002. Twenty-three shoulders in twenty-one patients were identified. The median
      duration of follow-up for the twenty shoulders that did not require revision
      surgery was 9.7 years. Nine shoulders had a partial-thickness tear, and fourteen
      had a full-thickness tear. The shoulders were assessed with regard to pain,
      functional outcome, and overall patient satisfaction. RESULTS: Patients with both
      partial and full-thickness rotator cuff tears had significant improvements in
      terms of overall pain (p < 0.05) and satisfaction (p < 0.05). Patients who had
      undergone repair of a partial-thickness tear had improved active elevation (from
      155 degrees to 180 degrees; p = 0.03), whereas patients who had undergone repair
      of a full-thickness tear did not have improved elevation. Six of the fourteen
      shoulders with a full-thickness tear had an unsatisfactory result, whereas only
      two of the nine shoulders with a partial-thickness tear had an unsatisfactory
      result. CONCLUSIONS: Rotator cuff repair in patients with rheumatoid arthritis
      can be challenging. However, durable pain relief and patient satisfaction can be
      achieved. Functional gains should not be expected in patients with full-thickness
      rotator cuff tears. Repair of the rotator cuff in patients with rheumatoid
      arthritis can be undertaken when nonoperative measures for pain relief have
      failed.

PMID- 16085620
TI  - Ultrasound diagnosis of peroneal tendon tears. A surgical correlation.
AB  - BACKGROUND: Musculoskeletal ultrasound is an established diagnostic technique for
      the assessment of tendon injuries. The purpose of the present study was to
      determine whether ultrasound is effective for evaluating peroneal tendon
      injuries, with surgical findings used as the standard of reference. METHODS:
      Fifty-eight patients with a suspected peroneal tendon injury were prospectively
      evaluated with use of dynamic ultrasound. Twenty-five patients were found to have
      peroneal tendon tears and were managed operatively. Five patients with normal
      peroneal tendons on ultrasound examination also were managed operatively for
      other reasons and are included in the series as the peroneal tendons were
      inspected at the time of the procedure. Ultrasound and surgical criteria were
      used to grade the peroneal tendons on a scale from grade 0 (normal tendon) to
      grade III (tendon rupture). RESULTS: Of the sixty tendons that were evaluated
      operatively, twenty-five were found to be torn. The sensitivity, specificity, and
      accuracy of ultrasonography were 100%, 85%, and 90%, respectively. CONCLUSIONS:
      The use of dynamic ultrasound is effective for determining the presence or
      absence of a peroneal tendon tear and should be considered a first-line
      diagnostic tool.

PMID- 16085621
TI  - Revision of the acetabular component without cement after total hip arthroplasty.
      A concise follow-up, at fifteen to nineteen years, of a previous report.
AB  - We previously reported our results at a minimum of three and seven years after
      use of a porous-coated acetabular metal shell in a consecutive series of 138
      revision total hip arthroplasties. The current report presents the longer-term
      outcomes of these procedures, at fifteen to nineteen years postoperatively. A
      total of twenty metal shells (14%) underwent repeat revision. Seven of the repeat
      revisions were performed because of recurrent dislocation, seven were done at the
      time of femoral revision surgery, and six were done because of infection.
      Nineteen of the revised shells were well fixed, and one was aseptically loose. Of
      the sixty-seven hips in which the acetabular component survived for more than
      fifteen years after the index operation, two (3%) required a change of the
      modular acetabular liner because of wear or osteolysis. Nine (16%) of the fifty
      seven hips with at least fifteen years of radiographic follow-up had an
      osteolytic lesion of >1 cm in diameter. The fifteen-year survival rate of the
      metal shells, with failure defined as revision because of loosening or as
      radiographic evidence of loosening, was 97%. Revision total hip arthroplasty with
      this cementless acetabular component has been followed by excellent component
      survivorship at fifteen years; the most common reasons for repeat revision were
      recurrent dislocation and infection.

PMID- 16085622
TI  - Long-term persistence of disability following severe lower-limb trauma. Results
      of a seven-year follow-up.
AB  - BACKGROUND: A recent study demonstrated that patients treated with amputation and
      those treated with reconstruction had comparable functional outcomes at two years
      following limb-threatening trauma. The present study was designed to determine
      whether those outcomes improved after two years, and whether differences
      according to the type of treatment emerged. METHODS: Three hundred and ninety
      seven patients who had undergone amputation or reconstruction of the lower
      extremity were interviewed by telephone at an average of eighty-four months after
      the injury. Functional outcomes were assessed with use of the physical and
      psychosocial subscores of the Sickness Impact Profile (SIP) and were compared
      with similar scores obtained at twenty-four months. RESULTS: On the average,
      physical and psychosocial functioning deteriorated between twenty-four and eighty
      four months after the injury. At eighty-four months, one-half of the patients had
      a physical SIP subscore of > or = 10 points, which is indicative of substantial
      disability, and only 34.5% had a score typical of a general population of similar
      age and gender. There were few significant differences in the outcomes according
      to the type of treatment, with two exceptions. Compared with patients treated
      with reconstruction for a tibial shaft fracture, those with only a severe soft
      tissue injury of the leg were 3.1 times more likely to have a physical SIP
      subscore of 5 points (p < 0.05) and those treated with a through-the-knee
      amputation were 11.5 times more likely to have a physical subscore of 5 points (p
      < 0.05). There were no significant differences in the psychosocial outcomes
      according to treatment group. Patient characteristics that were significantly
      associated with poorer outcomes included older age, female gender, nonwhite race,
      lower education level, living in a poor household, current or previous smoking,
      low self-efficacy, poor self-reported health status before the injury, and
      involvement with the legal system in an effort to obtain disability payments.
      Except for age, predictors of poor outcome were similar at twenty-four and eighty
      four months after the injury. CONCLUSIONS: The results confirm previous
      conclusions that reconstruction for the treatment of injuries below the distal
      part of the femur typically results in functional outcomes equivalent to those of
      amputation. Regardless of the treatment option, however, long-term functional
      outcomes are poor. Priority should be given to efforts to improve post-acute-care
      services that address secondary conditions that compromise optimal recovery.

PMID- 16085623
TI  - Dislocation rate after hip hemiarthroplasty in patients with tumor-related
      conditions.
AB  - BACKGROUND: Hemiarthroplasty is frequently used to treat femoral neck
      insufficiency resulting from neoplastic disease in the proximal part of the
      femur. The authors of a recent study analyzed the dislocation rates following
      hemiarthroplasty but excluded patients with tumor involvement of the site of the
      surgery as they hypothesized that the dislocation rates would be markedly higher
      in such patients. The current study was performed to compare the dislocation rate
      following hemiarthroplasties performed in patients without tumor involvement with
      the rate following hemiarthroplasties in patients with tumor involvement of the
      surgical site. METHODS: Patients who had undergone hemiarthroplasty following
      resection of a tumor involving the proximal part of the femur were identified in
      a total joint registry, and the patients' charts were reviewed retrospectively to
      determine dislocation rates, preoperative conditions, and postoperative outcomes
      and treatments. Between 1974 and 2001, 1812 patients were treated with
      hemiarthroplasty for reasons other than tumor involvement and 320
      hemiarthroplasties were performed because of tumor-related conditions. The
      patients who were treated for a tumor-related condition were younger, and a
      higher proportion of them were men. RESULTS: The ten-year dislocation rate after
      the hemiarthroplasties performed for tumor-related conditions (10.9%) was higher
      than that following the hemiarthroplasties performed for non-tumor-related
      conditions (2.1%) (p = 0.002). The median time to dislocation in the patients
      with a tumor-related condition (twenty-four days) was shorter than that for the
      patients without tumor involvement (thirty-seven days). Preservation of the
      greater trochanter in patients with tumor involvement did not have a significant
      influence on the dislocation rate, but it showed a favorable trend toward
      decreasing that rate (hazard ratio = 3.5, p = 0.06). CONCLUSIONS: The short-term
      and long-term dislocation rates associated with hemiarthroplasties performed for
      a tumor-related condition at the site of the surgery were significantly higher
      than those associated with hemiarthroplasties performed for reasons other than
      tumor involvement. Preservation of the greater trochanter showed a trend toward
      decreasing the likelihood of dislocation following the hemiarthroplasty, and it
      was more influential than the level of resection and the extent of soft-tissue
      compromise. We think that preservation of the greater trochanter should be
      attempted when it is justifiable according to the principles of oncologic
      surgery.

PMID- 16085624
TI  - Clinical performance of a Durasul highly cross-linked polyethylene acetabular
      liner for total hip arthroplasty at five years.
AB  - BACKGROUND: Highly cross-linked polyethylene is currently the most common
      articulation surface used for total hip arthroplasty. The hypothesis of the
      present study was that the Durasul highly cross-linked polyethylene acetabular
      liner would have less wear at five years than would a conventional polyethylene
      liner used in association with the same total hip replacement system. METHODS:
      Forty-three consecutive patients (fifty hips) underwent total hip replacement
      with an uncemented titanium porous-coated metal cup and a Durasul liner that was
      mated with a 28-mm cobalt-chromium femoral head. Thirty-one patients (thirty
      seven hips) were followed for at least five years. Thirty-five other patients
      (thirty-seven hips) underwent total hip arthroplasty with the same system but
      with a conventional polyethylene liner, and these patients also were followed for
      five years. Clinical assessment was performed with use of the Harris hip score
      and a patient self-assessment examination. Radiographic analysis included
      measurements of acetabular component position, fixation, and osteolysis. Femoral
      head penetration of the Durasul liners was compared with that of the conventional
      liners. RESULTS: The clinical results as determined on the basis of Harris hip
      scores and patient self-assessment examinations did not differ between the
      Durasul group and the control group. The mean bedding-in penetration was 0.054 +/
      0.07 mm for the Durasul group and 0.059 +/- 0.154 mm for the control group. The
      subsequent penetration, with elimination of the bedding-in wear, resulted in a
      linear wear rate of 0.029 +/- 0.02 mm per year for the Durasul group, compared
      with 0.065 +/- 0.03 mm per year for the control group (p < 0.005). The annual
      penetration at one and five years was 0.074 mm and 0.011 mm, respectively, for
      the Durasul group, compared with 0.151 mm and 0.04 mm, respectively, for the
      control group. CONCLUSIONS: While the qualitative wear pattern of the highly
      cross-linked polyethylene liner was the same as that of the conventional
      polyethylene liner, the annual linear wear rate was 45% of that seen with the
      conventional polyethylene liner. Therefore, we believe that these early data
      support the continued use of this highly cross-linked polyethylene liner for
      total hip arthroplasty.

PMID- 16085625
TI  - Disappearance of a cervical spine chordoma after nonoperative treatment. A case
      report.

PMID- 16085626
TI  - Failure of fresh-frozen radial head allografts in the treatment of Essex-Lopresti
      injury. A report of four cases.

PMID- 16085627
TI  - Brachial plexus palsy after intramedullary fixation of a clavicular fracture. A
      report of three cases.

PMID- 16085628
TI  - Histopathologic analysis of human vertebral bodies after vertebral augmentation
      with polymethylmethacrylate with use of an inflatable bone tamp. A case report.

PMID- 16085629
TI  - Knee pain and swelling due to Crohn disease. A case report.

PMID- 16085630
TI  - Fibrous dysplasia. Pathophysiology, evaluation, and treatment.
AB  - Fibrous dysplasia is a common benign skeletal lesion that may involve one bone
      (monostotic) or multiple bones (polyostotic) and occurs throughout the skeleton
      with a predilection for the long bones, ribs, and craniofacial bones. The
      etiology of fibrous dysplasia has been linked to an activating mutation in the
      gene that encodes the alpha subunit of stimulatory G protein (G(s)alpha) located
      at 20q13.2-13.3. Most lesions are monostotic, asymptomatic, and identified
      incidentally and can be treated with clinical observation and patient education.
      Bisphosphonate therapy may help to improve function, decrease pain, and lower
      fracture risk in appropriately selected patients with fibrous dysplasia. Surgery
      is indicated for confirmatory biopsy, correction of deformity, prevention of
      pathologic fracture, and/or eradication of symptomatic lesions. The use of
      cortical grafts is preferred over cancellous grafts or bone-graft substitutes
      because of the superior physical qualities of remodeled cortical bone.

PMID- 16085631
TI  - Orthopaedic gifts.

PMID- 16085632
TI  - Anterior cruciate ligament reconstruction: bone-patellar tendon-bone compared
      with double semitendinosus and gracilis tendon grafts.

PMID- 16085633
TI  - Catastrophic complications of minimally invasive hip surgery.

PMID- 16085634
TI  - The effect of intra-articular methadone on postoperative pain following anterior
      cruciate ligament reconstruction.

PMID- 16085635
TI  - Radiologists' interpretations of magnetic resonance images of the knee.

PMID- 16085636
TI  - Ankle stress test for predicting the need for surgical fixation of isolated
      fibular fractures: statistical analysis.

PMID- 16085637
TI  - Distal femoral varus osteotomy for osteoarthritis of the knee.

PMID- 16085638
TI  - Long-term outcomes did not differ after resurfacing or nonresurfacing in total
      knee arthroplasty.

PMID- 16085639
TI  - Functional bracing was no better than nonbracing after anterior cruciate ligament
      repair.

PMID- 16085640
TI  - Early application of hip spica led to higher malunion rates in pediatric femoral
      fracture.

PMID- 16085641
TI  - What's new in spine surgery.

PMID- 16085642
TI  - Targeted intestinal overexpression of the immediate early gene tis7 in transgenic
      mice increases triglyceride absorption and adiposity.
AB  - Following loss of functional small bowel surface area due to surgical resection,
      the remnant gut undergoes an adaptive response characterized by increased crypt
      cell proliferation and enhanced villus height and crypt depth, resulting in
      augmented intestinal nutrient absorptive capacity. Previous studies showed that
      expression of the immediate early gene tis7 is markedly up-regulated in
      intestinal enterocytes during the adaptive response. To study its role in the
      enterocyte, transgenic mice were generated that specifically overexpress TIS7 in
      the gut. Nucleotides -596 to +21 of the rat liver fatty acid-binding protein
      promoter were used to direct abundant overexpression of TIS7 into small
      intestinal upper crypt and villus enterocytes. TIS7 transgenic mice had increased
      total body adiposity and decreased lean muscle mass compared with normal
      littermates. Oxygen consumption levels, body weight, surface area, and small
      bowel weight were decreased. On a high fat diet, transgenic mice exhibited a more
      rapid and proportionately greater gain in body weight with persistently elevated
      total body adiposity and increased hepatic fat accumulation. Bolus fat feeding
      resulted in a greater increase in serum triglyceride levels and an accelerated
      appearance of enterocytic, lamina propria, and hepatic fat. Changes in fat
      homeostasis were linked to increased expression of genes involved in enterocytic
      triglyceride metabolism and changes in growth with decreased insulin-like growth
      factor-1 expression. Thus, TIS7 overexpression in the intestine altered growth,
      metabolic rate, adiposity, and intestinal triglyceride absorption. These results
      suggest that TIS7 is a unique mediator of nutrient absorptive and metabolic
      adaptation following gut resection.

PMID- 16085643
TI  - Histidylated lipid-modified Sendai viral envelopes mediate enhanced membrane
      fusion and potentiate targeted gene delivery.
AB  - Recent studies have demonstrated that covalent grafting of a single histidine
      residue into a twin-chain aliphatic hydrocarbon compound enhances its endosome
      disrupting properties and thereby generates an excellent DNA transfection system.
      Significant increase in gene delivery efficiencies has thus been obtained by
      using endosome-disrupting multiple histidine functionalities in the molecular
      architecture of various cationic polymers. To take advantage of this unique
      feature, we have incorporated L-histidine (N,N-di-n-hexadecylamine) ethylamide
      (L(H)) in the membrane of hepatocyte-specific Sendai virosomes containing only
      the fusion protein (F-virosomes (Process for Producing a Targeted Gene (Sarkar,
      D. P., Ramani, K., Bora, R. S., Kumar, M., and Tyagi, S. K. (November 4, 1997) U.
      S. Patent 5,683,866))). Such L(H)-modified virosomal envelopes were four times
      more (p < 0.001) active in terms of fusion with its target cell membrane. On the
      other hand, the presence of L(H) in reconstituted influenza and vesicular
      stomatitis virus envelopes failed to enhance spike glycoprotein-induced membrane
      fusion with host cell membrane. Circular dichroism and limited proteolysis
      experiments with F-virosomes indicated that the presence of L(H) leads to
      conformational changes in the F protein. The molecular mechanism associated with
      the increased membrane fusion induced by L(H) has been addressed in the light of
      fusion-competent conformational change in F protein. Such enhancement of fusion
      resulted in a highly efficient gene delivery system specific for liver cells in
      culture and in whole animals.

PMID- 16085644
TI  - Death-associated protein kinase as a sensor of mitochondrial membrane potential:
      role of lysosome in mitochondrial toxin-induced cell death.
AB  - We have investigated here the mechanism of dephosphorylation and activation of
      death-associated protein kinase (DAPK) and the role of lysosome in neuroblastoma
      cells (SH-SY5Y) treated with mitochondrial toxins, such as MPP(+) and rotenone.
      Mitochondrial respiratory chain inhibitors and uncouplers decreased mitochondrial
      membrane potential leading to DAPK dephosphorylation and activation. The class
      III phosphoinositide 3-kinase inhibitors attenuated DAPK dephosphorylation
      induced by mitochondrial toxins. Complex I inhibition by mitochondrial toxins
      (e.g. MPP(+)) resulted in mitochondrial swelling and lysosome reduction.
      Inhibition of class III phosphoinositide 3-kinase attenuated MPP(+)-induced
      lysosome reduction and cell death. The role of DAPK as a sensor of mitochondrial
      membrane potential in mitochondrial diseases was addressed.

PMID- 16085645
TI  - Both rotor and stator subunits are necessary for efficient binding of F1 to F0 in
      functionally assembled Escherichia coli ATP synthase.
AB  - In F1F0-ATP synthase, the subunit b2delta complex comprises the peripheral stator
      bound to subunit a in F0 and to the alpha3beta3 hexamer of F1. During catalysis,
      ATP turnover is coupled via an elastic rotary mechanism to proton translocation.
      Thus, the stator has to withstand the generated rotor torque, which implies tight
      interactions of the stator and rotor subunits. To quantitatively characterize the
      contribution of the F0 subunits to the binding of F1 within the assembled
      holoenzyme, the isolated subunit b dimer, ab2 subcomplex, and fully assembled F0
      complex were specifically labeled with tetramethylrhodamine-5-maleimide at bCys64
      and functionally reconstituted into liposomes. Proteoliposomes were then titrated
      with increasing amounts of Cy5-maleimide-labeled F1 (at gammaCys106 and analyzed
      by single-molecule fluorescence resonance energy transfer. The data revealed F1
      dissociation constants of 2.7 nm for the binding of F0 and 9-10 nm for both the
      ab2 subcomplex and subunit b dimer. This indicates that both rotor and stator
      components of F0 contribute to F1 binding affinity in the assembled holoenzyme.
      The subunit c ring plays a crucial role in the binding of F1 to F0, whereas
      subunit a does not contribute significantly.

PMID- 16085647
TI  - JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin
      resistance in 3T3-L1 adipocytes.
AB  - Lipid infusion and high fat feeding are established causes of systemic and
      adipose tissue insulin resistance. In this study, we treated 3T3-L1 adipocytes
      with a mixture of free fatty acids (FFAs) to investigate the molecular mechanisms
      underlying fat-induced insulin resistance. FFA treatment impaired insulin
      receptor-mediated signal transduction and decreased insulin-stimulated GLUT4
      translocation and glucose transport. FFAs activated the stress/inflammatory
      kinases c-Jun N-terminal kinase (JNK) and IKKbeta, and the suppressor of cytokine
      signaling protein 3, increased secretion of the inflammatory cytokine tumor
      necrosis factor (TNF)-alpha, and decreased secretion of adiponectin into the
      medium. RNA interference-mediated down-regulation of JNK blocked JNK activation
      and prevented most of the FFA-induced defects in insulin action. Blockade of TNF
      alpha signaling with neutralizing antibodies to TNF-alpha or its receptors or
      with a dominant negative TNF-alpha peptide had a partial effect to inhibit FFA
      induced cellular insulin resistance. We found that JNK activation by FFAs was not
      inhibited by blocking TNF-alpha signaling, whereas the FFA-induced increase in
      TNF-alpha secretion was inhibited by RNA interference-mediated JNK knockdown.
      Together, these results indicate that 1) JNK can be activated by FFAs through TNF
      alpha-independent mechanisms, 2) activated JNK is a major contributor to FFA
      induced cellular insulin resistance, and 3) TNF-alpha is an autocrine/paracrine
      downstream effector of activated JNK that can also mediate insulin resistance.

PMID- 16085646
TI  - Physiological and receptor-selective retinoids modulate interferon gamma
      signaling by increasing the expression, nuclear localization, and functional
      activity of interferon regulatory factor-1.
AB  - Synergistic actions between all-trans-retinoic acid (atRA) and interferon gamma
      (IFNgamma) on modulation of cellular functions have been reported both in vitro
      and in vivo. However, the mechanism of atRA-mediated regulation of IFNgamma
      signaling is poorly understood. In this study, we have used the human lung
      epithelial cell line A549 to examine the effect of atRA on IFNgamma-induced
      expression of IFN regulatory factor-1 (IRF-1), an important transcription factor
      involved in cell growth and apoptosis, differentiation, and antiviral and
      antibacterial immune responses. At least 4 h of pretreatment with atRA followed
      by suboptimal concentrations of IFNgamma induced a faster, higher, and more
      stable expression of IRF-1 than IFNgamma alone. Actinomycin D completely blocked
      the induction of IRF-1 by the combination, suggesting regulation at the
      transcriptional level. Further, we found that activation of signal transducer and
      activator of transcription-1 was induced more dramatically by atRA and IFNgamma
      than by IFNgamma alone. Expression of IFNgamma receptor-1 on the cell surface was
      also increased upon atRA pretreatment. Experiments using receptor-selective
      retinoids revealed that ligands for retinoic acid receptor-alpha (RARalpha),
      including atRA, 9-cis-retinoic acid, and Am580, sequentially increased the levels
      of IFNgamma receptor-1, activated signal transducer and activator of
      transcription-1, and IRF-1 and that an RARalpha antagonist was able to inhibit
      the effects of atRA and Am580. In addition, atRA pretreatment affected the
      transcriptional functions of IFNgamma-induced IRF-1, increasing its nuclear
      localization and DNA binding activity as well as the transcript levels of IRF-1
      target genes. These results suggest that atRA, an RARalpha ligand, regulates
      IFNgamma-induced IRF-1 by affecting multiple components of the IFNgamma signaling
      pathway, from the plasma membrane to the nuclear transcription factors.

PMID- 16085648
TI  - Huntingtin associates with acidic phospholipids at the plasma membrane.
AB  - We have identified a domain in the N terminus of huntingtin that binds to
      membranes. A three-dimensional homology model of the structure of the binding
      domain predicts helical HEAT repeats, which emanate a positive electrostatic
      potential, consistent with a charge-based mechanism for membrane association. An
      amphipathic helix capable of inserting into pure lipid bilayers may serve to
      anchor huntingtin to the membrane. In cells, N-terminal huntingtin fragments
      targeted to regions of plasma membrane enriched in phosphatidylinositol 4,5
      bisphosphate, receptor bound-transferrin, and endogenous huntingtin. N-terminal
      huntingtin fragments with an expanded polyglutamine tract aberrantly localized to
      intracellular regions instead of plasma membrane. Our data support a new model in
      which huntingtin directly binds membranes through electrostatic interactions with
      acidic phospholipids.

PMID- 16085649
TI  - Electron transfer within complex II. Succinate:ubiquinone oxidoreductase of
      Escherichia coli.
AB  - Electron transfer within Escherichia coli succinate:ubiquinone oxidoreductase has
      been examined by the pulse radiolysis technique using spectrophotometric
      detection. Electrons have been introduced into the protein by the bimolecular
      reaction with quantified concentrations of the low potential N-methylnicotinamide
      radical at a rate constant of 7 x 10(8) M(-1) s(-1). Two redox-active centers in
      the protein are initially reduced, assigned as the high potential [3Fe-4S] center
      and the bound ubiquinone, followed by intramolecular equilibration with the b
      heme in both cases. Electron equilibration at 25 degrees C from the
      ubisemiquinone proceeds with an observed rate constant of 7,200 s(-1) and from
      the more distant [3Fe-4S] reduced center at a rate constant of 1,200 s(-1).
      Temperature dependence studies have revealed that both reactions have large free
      energies of activation, with deltaG(double dagger) values of +0.53 and +0.58 eV,
      respectively. Cumulative spectral changes, as well as accompanying decreases in
      the rates of intramolecular electron transfer, observed upon adding electrons to
      progressively reduced protein, indicate that 4 electrons must be introduced into
      the protein before the heme center is fully reduced. Overall, evidence is
      presented that the heme, far from being a bystander in the efficient transfer of
      reducing equivalents from succinate to the ubiquinone via the flavin-Fe/S
      centers, plays a pivotal role in providing a lower energy pathway for the
      transfer of an electron from the high potential [3Fe-4S] center to ubiquinone.

PMID- 16085650
TI  - Active-site peptide "fingerprinting" of glycosidases in complex mixtures by mass
      spectrometry. Discovery of a novel retaining beta-1,4-glycanase in Cellulomonas
      fimi.
AB  - New proteomics methods are required for targeting and identification of subsets
      of a proteome in an activity-based fashion. Here, we report the first gel-free,
      mass spectrometry-based strategy for mechanism-based profiling of retaining beta
      endoglycosidases in complex proteomes. Using a biotinylated, cleavable 2-deoxy-2
      fluoroxylobioside inactivator, we have isolated and identified the active-site
      peptides of target retaining beta-1,4-glycanases in systems of increasing
      complexity: pure enzymes, artificial proteomes, and the secreted proteome of the
      aerobic mesophilic soil bacterium Cellulomonas fimi. The active-site peptide of a
      new C. fimi beta-1,4-glycanase was identified in this manner, and the peptide
      sequence, which includes the catalytic nucleophile, is highly conserved among
      glycosidase family 10 members. The glycanase gene (GenBank accession number
      DQ146941) was cloned using inverse PCR techniques, and the protein was found to
      comprise a catalytic domain that shares approximately 70% sequence identity with
      those of xylanases from Streptomyces sp. and a family 2b carbohydrate-binding
      module. The new glycanase hydrolyzes natural and artificial xylo-configured
      substrates more efficiently than their cello-configured counterparts. It has a pH
      dependence very similar to that of known C. fimi retaining glycanases.

PMID- 16085651
TI  - Converting a {beta}-glycosidase into a {beta}-transglycosidase by directed
      evolution.
AB  - Directed evolution was applied to the beta-glycosidase of Thermus thermophilus in
      order to increase its ability to synthesize oligosaccharide by
      transglycosylation. Wild-type enzyme was able to transfer the glycosyl residue
      with a yield of 50% by self-condensation and of about 8% by transglycosylation on
      disaccharides without nitrophenyl at their reducing end. By using a simple
      screening procedure, we could produce mutant enzymes possessing a high
      transferase activity. In one step of random mutagenesis and in vitro
      recombination, the hydrolysis of substrates and of transglycosylation products
      was considerably reduced. For certain mutants, synthesis by self-condensation of
      nitrophenyl glycosides became nearly quantitative, whereas synthesis by
      transglycosylation on maltose and on cellobiose could reach 60 and 75%,
      respectively. Because the most efficient mutations, F401S and N282T, were located
      just in front of the subsite (-1), molecular modeling techniques were used to
      explain their effects on the synthesis reaction; we can suggest that
      repositioning of the glycone in the (-1) subsite together with a better fit of
      the acceptor in the (+1) subsite might favor the attack of a glycosyl acceptor in
      the mutant at the expense of water. Thus these new transglycosidases constitute
      an interesting alternative for the synthesis of oligosaccharides by using stable
      and accessible donor substrates.

PMID- 16085652
TI  - Structural analysis of Siah1-Siah-interacting protein interactions and insights
      into the assembly of an E3 ligase multiprotein complex.
AB  - Siah1 is the central component of a multiprotein E3 ubiquitin ligase complex that
      targets beta-catenin for destruction in response to p53 activation. The E3
      complex comprises, in addition to Siah1, Siah-interacting protein (SIP), the
      adaptor protein Skp1, and the F-box protein Ebi. Here we show that SIP engages
      Siah1 by means of two elements, both of which are required for mediating beta
      catenin destruction in cells. An N-terminal dimerization domain of SIP sits
      across the saddle-shaped upper surface of Siah1, with two extended legs packing
      against the sides of Siah1 by means of a consensus PXAXVXP motif that is common
      to a family of Siah-binding proteins. The C-terminal domain of SIP, which binds
      to Skp1, protrudes from the lower surface of Siah1, and we propose that this
      surface provides the scaffold for bringing substrate and the E2 enzyme into
      apposition in the functional complex.

PMID- 16085653
TI  - Mechanisms of statin-mediated inhibition of small G-protein function.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been
      reported to reduce the risk of Alzheimer disease. We have shown previously that
      statins inhibit a beta-amyloid (Abeta)-mediated inflammatory response through
      mechanisms independent of cholesterol reduction. Specifically, statins exert anti
      inflammatory actions through their ability to prevent the isoprenylation of
      members of the Rho family of small G-proteins, resulting in the functional
      inactivation of these G-proteins. We report that statin treatment of microglia
      results in perturbation of the cytoskeleton and morphological changes due to
      alteration in Rho family function. Statins also block Abeta-stimulated
      phagocytosis through inhibition of Rac action. Paradoxically, the statin-mediated
      inactivation of G-protein function was associated with increased GTP loading of
      Rac and RhoA, and this effect was observed in myeloid lineage cells and other
      cell types. Statin treatment disrupted the interaction of Rac with its negative
      regulator the Rho guanine nucleotide dissociation inhibitor (RhoGDI), an
      interaction that is dependent on protein isoprenylation. We propose that lack of
      negative regulation accounts for the increased GTP loading. Isoprenylation of Rac
      is also required for efficient interaction with the plasma membrane, and we
      report that statin treatment dramatically reduces the capacity of Rac to interact
      with membranes. These results suggest a mechanism by which statins inhibit the
      actions of Rho GTPases and attenuate Abeta-stimulated inflammation.

PMID- 16085654
TI  - Srs2 helicase of Saccharomyces cerevisiae selectively unwinds triplet repeat DNA.
AB  - Trinucleotide repeat expansions are the mutational cause of at least 15 genetic
      diseases. In vitro, single-stranded triplet repeat DNA forms highly stable
      hairpins, depending on repeat sequence, and a strong correlation exists between
      hairpin-forming ability and the risk of expansion in vivo. Hairpins are viewed,
      therefore, as likely mutagenic precursors to expansions. If a helicase unwinds
      the hairpin, it would be less likely to expand. Previous work indicated that
      yeast Srs2 DNA helicase selectively blocks expansions in vivo (Bhattacharyya, S.,
      and Lahue, R. S. (2004) Mol. Cell. Biol. 24, 7324-7330). For example, srs2
      mutants, including an ATPase-defective point mutant, exhibit substantially higher
      expansion rates than wild type controls. In contrast, mutation of another
      helicase gene, SGS1, had little effect on expansion rates. These findings
      prompted the idea that Srs2 might selectively unwind triplet repeat hairpins. In
      this study, DNA helicase assays were performed with purified Srs2, Sgs1, and
      Escherichia coli UvrD (DNA helicase II). Srs2 shows substantially faster
      unwinding than Sgs1 or UvrD on partial duplex substrates containing (CTG) x (CTG)
      sequences, provided that Srs2 encounters the triplet repeat DNA immediately on
      entering the duplex. Srs2 was also faster at unwinding (CAG) x (CAG)- and (CCG) x
      (CCG)-containing substrates and an intramolecular (CTG) x (CTG) hairpin. In
      contrast, all three enzymes unwind about equally well control substrates with
      either Watson-Crick base pairs or mismatched substrates with non-CNG repeats.
      Overall, the selective unwinding activity of Srs2 on triplet repeat hairpin DNA
      helps explain the genetic evidence that Srs2, not the RecQ homolog Sgs1, is a
      preferred helicase for preventing expansions.

PMID- 16085656
TI  - Characterization of phosphatidylinositol-specific phospholipase C (PI-PLC) from
      Lilium daviddi pollen.
AB  - The phosphatidylinositol-specific phospholipase C (PI-PLC) activity is detected
      in purified Lilium pollen protoplasts. Two PI-PLC full length cDNAs, LdPLC1 and
      LdPLC2, were isolated from pollen of Lilium daviddi. The amino acid sequences for
      the two PI-PLCs deduced from the two cDNA sequences contain X, Y catalytic motifs
      and C2 domains. Blast analysis shows that LdPLCs have 60-65% identities to the PI
      PLCs from other plant species. Both recombinant PI-PLCs proteins expressed in E.
      coli cells show the PIP(2)-hydrolyzing activity. The RT-PCR analysis shows that
      both of them are expressed in pollen grains, whereas expression level of LdPLC2
      is induced in germinating pollen. The exogenous purified calmodulin (CaM) is able
      to stimulate the activity of the PI-PLC when it is added into the pollen
      protoplast medium, while anti-CaM antibody suppresses the stimulation effect
      caused by exogenous CaM. PI-PLC activity is enhanced by G protein agonist cholera
      toxin and decreased by G protein antagonist pertussis toxin. Increasing in PI-PLC
      activity caused by exogenous purified CaM is also inhibited by pertussis toxin. A
      PI-PLC inhibitor, U-73122, inhibited the stimulation of PI-PLC activity caused by
      cholera toxin and it also leads to the decrease of [Ca(2+)](cyt) in pollen
      grains. Those results suggest that the PPI-PLC signaling pathway is present in
      Lilium daviddi pollen, and PI-PLC activity might be regulated by a heterotrimeric
      G protein and extracellular CaM.

PMID- 16085657
TI  - Stability constraints and protein evolution: the role of chain length,
      composition and disulfide bonds.
AB  - Stability of the native state is an essential requirement in protein evolution
      and design. Here we investigated the interplay between chain length and stability
      constraints using a simple model of protein folding and a statistical study of
      the Protein Data Bank. We distinguish two types of stability of the native state:
      with respect to the unfolded state (unfolding stability) and with respect to
      misfolded configurations (misfolding stability). Several contributions to
      stability are evaluated and their correlations are disentangled through principal
      components analysis, with the following main results. (1) We show that longer
      proteins can fulfil more easily the requirements of unfolding and misfolding
      stability, because they have a higher number of native interactions per residue.
      Consistently, in longer proteins native interactions are weaker and they are less
      optimized with respect to non-native interactions. (2) Stability against
      misfolding is negatively correlated with the strength of native interactions,
      which is related to hydrophobicity. Hence there is a trade-off between unfolding
      and misfolding stability. This trade-off is influenced by protein length: less
      hydrophobic sequences are observed in very long proteins. (3) The number of
      disulfide bonds is positively correlated with the deficit of free energy
      stabilizing the native state. Chain length and the number of disulfide bonds per
      residue are negatively correlated in proteins with short chains and uncorrelated
      in proteins with long chains. (4) The number of salt bridges per residue and per
      native contact increases with chain length. We interpret these observations as an
      indication that the constraints imposed by unfolding stability are less demanding
      in long proteins and they are further reduced by the competing requirement for
      stability against misfolding. In particular, disulfide bonds appear to be
      positively selected in short proteins, whereas they evolve in an effectively
      neutral way in long proteins.

PMID- 16085658
TI  - Single blind, randomised, comparative study of the Bug Buster kit and over the
      counter pediculicide treatments against head lice in the United Kingdom.
AB  - OBJECTIVE: To compare the effectiveness of the Bug Buster kit with a single
      treatment of over the counter pediculicides for eliminating head lice. DESIGN:
      Single blind, multicentre, randomised, comparative clinical study. SETTING: Four
      counties in England and one county in Scotland. PARTICIPANTS: 133 young people
      aged 2-15 years with head louse infestation: 56 were allocated to the Bug Buster
      kit and 70 to pediculicide treatment. INTERVENTIONS: Home use of proprietary
      pediculicides (organophosphate or pyrethroid) or the Bug Buster kit. MAIN OUTCOME
      MEASURE: Presence of head lice 2-4 days after end of treatment: day 5 for the
      pediculicides and day 15 for the Bug Buster kit. RESULTS: The cure rate using the
      Bug Buster kit was significantly greater than that for the pediculicides (57% v
      13%; relative risk 4.4, 95% confidence interval 2.3 to 8.5). Number needed to
      treat for the Bug Buster kit compared with the pediculicides was 2.26.
      CONCLUSION: The Bug Buster kit was the most effective over the counter treatment
      for head louse infestation in the community when compared with pediculicides.

PMID- 16085659
TI  - Inadvertent transgenesis by conventional ICSI in mice.
AB  - BACKGROUND: ICSI is a relatively new treatment for human male-related
      infertility, as well as an efficient method for the production of transgenic
      animals by injecting into the oocyte sperm previously incubated with foreign DNA.
      As semen samples collected in human infertility clinics are frequently
      contaminated with bacteria, one risk associated with the ICSI procedure is the
      injection of foreign, sperm-associated exogenous DNA into the oocyte, and the
      generation of transgenic offspring. METHODS: To analyse this possibility, ICSI
      was performed in mouse oocytes with frozen-thawed and Percoll-treated fresh sperm
      samples intentionally contaminated with plasmid EGFP-transformed E. coli bacteria
      or medium from which these bacteria were washed. Fertilized embryos were cultured
      in vitro until morula/blastocyst stage, transferred into pseudopregnant females,
      and at day 14, fetuses and reabsorptions were analysed by PCR for the genomic
      presence of integrated plasmid and/or bacterial DNA. RESULTS: Independently of
      the sperm pretreatment tested, transgenesis was produced. CONCLUSIONS:
      Inadvertent transgenesis by conventional ICSI is a possibility that should not be
      neglected. Particular precautions, such as full bacteriological semen
      examinations and effective antibiotic semen pretreatments, should be taken in
      human infertility clinics, in order to exclude the possibility of accidental
      transgenesis.

PMID- 16085660
TI  - Similar endometrial development in oocyte donors treated with either high- or
      standard-dose GnRH antagonist compared to treatment with a GnRH agonist or in
      natural cycles.
AB  - BACKGROUND: This descriptive study evaluates the impact on endometrial
      development of standard and high doses of a GnRH antagonist in stimulated cycles
      compared with GnRH agonist and natural cycles. METHODS: Thirty-one oocyte donors
      were treated with a combination of rFSH and 0.25 mg/day ganirelix (standard
      dose), 2 mg/day ganirelix (high dose) or 0.6 mg/day buserelin (long protocol).
      Vaginal progesterone (200 mg/day) was administered in the luteal phase.
      Endometrial biopsies were performed 2 and 7 days after HCG administration.
      Additional biopsies were carried out in a subset of 12 subjects, 2 and 7 days
      following the LH peak of their previous natural cycle. Biopsies were evaluated
      histologically and by scanning electron microscopy. Gene expression profiles were
      also studied. RESULTS: At HCG +2, all the parameters studied were similar in all
      the groups and comparable to those observed in the natural cycle. At HCG +7,
      endometrial dating, steroid receptors and the presence of pinopodes were
      comparable in both GnRH antagonist groups and in the natural cycle. In buserelin
      group, endometrial dating and pinopode expression suggested an arrested
      endometrial development. For window of implantation genes, expression patterns
      were closer to those in the natural cycle following standard- or high-dose
      ganirelix than after buserelin administration. CONCLUSION: No relevant alteration
      was observed in the endometrial development in the early and mid-luteal phases in
      women undergoing controlled ovarian stimulation for oocyte donation following
      daily treatment with a standard- or high-dose GnRH antagonist. In addition, the
      endometrial development after GnRH antagonist mimics the natural endometrium more
      closely than after GnRH agonist.

PMID- 16085661
TI  - Influence of different hormonal regimens on endometrial microvascular density and
      VEGF expression in women suffering from breakthrough bleeding.
AB  - BACKGROUND: The aim of this study was to quantify blood vessel density (BVD) and
      immunoreactive vascular endothelial growth factor (VEGF) levels in endometrial
      biopsies taken from women suffering breakthrough bleeding (BTB) under different
      exogenous hormonal regimes. METHODS: Endometrial biopsies from women in Melbourne
      with BTB were divided into four groups: combined-continuous hormone therapy (HT)
      (estrogen and progestin taken daily), cyclical HT (daily estrogen with progestin
      for 14 days each cycle), progestin-only, or no HT. Subjects from Barcelona were
      using the Mirena intrauterine levonorgestrel-releasing system for contraceptive
      purposes, with menstrual diaries for classification into four groups (amenorrhea,
      infrequent, regular and prolonged). Control biopsies from Melbourne were included
      in the study. Endometrial samples were immunostained for VEGF and blood vessel
      localization using an antibody to CD34. RESULTS: Results showed that BVD was
      significantly reduced in the progestin-only treated group compared with the other
      three treatment groups (P = 0.028). In addition, all four Mirena BTB groups had
      significantly reduced BVD compared with controls. Considerable heterogeneity was
      observed in VEGF immunostaining within and between individual samples with no
      major differences between HT or Mirena. CONCLUSION: These results provide strong
      evidence that unopposed progestins reduce endometrial BVD and that there is no
      link between VEGF immunostaining and BVD or BTB.

PMID- 16085662
TI  - Subclavian vein thrombosis following IVF and ovarian hyperstimulation: a case
      report.
AB  - Thromboembolic phenomena are a serious consequence of assisted reproductive
      technology. We present a case of upper extremity deep vein thrombosis (DVT) at 7
      weeks gestation following ovarian hyperstimulation syndrome (OHSS) and IVF. Three
      weeks after recovering from OHSS, the patient presented with left neck pain and
      swelling. Ultrasound revealed a thrombus in the left jugular vein and left
      subclavian vein. Low molecular weight heparin (LMWH) was initiated with symptom
      resolution within 1 week. The patient remained on LWMH throughout her pregnancy
      and delivered at term. A literature review showed 97 published cases of
      thromboembolism following ovulation induction. A majority of these cases was
      associated with OHSS and pregnancy and the site of involvement was predominantly
      in the upper extremity and neck. Infertility physicians and obstetricians should
      be aware of this complication and keep in mind that it may occur weeks after
      resolution of OHSS symptoms.

PMID- 16085663
TI  - Cycle-dependent expression of macrophage migration inhibitory factor in the human
      endometrium.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a multifunctional
      cytokine that was shown to promote angiogenesis and tissue remodelling. Our
      previous studies identified MIF as one of the principal bioactive molecules
      involved in endothelial cell proliferation released by ectopic endometrial cells.
      METHODS AND RESULTS: In the present study, we examined the expression of MIF in
      the human endometrium and found an interesting distribution and temporal pattern
      of expression throughout the menstrual cycle. Immunoreactive MIF was predominant
      in the glands and surface epithelium. Dual immunofluorescence analysis further
      identified endothelial cells, macrophages and T-lymphocytes as cells markedly
      expressing MIF in the stroma. Quantitative assessment of MIF protein showed a
      regulated cycle phase-dependent expression pattern. MIF expression increased in
      the late proliferative/early Secretory phase of the menstrual cycle was moderate
      during the receptive phase or what is commonly called the implantation window
      before increasing again at the end of the cycle. This pattern paralleled MIF mRNA
      expression determined by northern blot. CONCLUSION: The cycle phase-specific
      expression of MIF suggests a tight regulation and perhaps different roles for
      this factor in the reparative, reproductive and inflammatory-like processes that
      occur in human endometrium during every menstrual cycle.

PMID- 16085664
TI  - Hysteroscopic permanent tubal sterilization using a nitinol-dacron intratubal
      device without anaesthesia in the outpatient setting: procedure feasibility and
      effectiveness.
AB  - BACKGROUND: Hysteroscopic permanent tubal sterilization has recently been
      introduced, resulting in a non-invasive, safe and effective technique. The aim of
      this study was to assess the feasibility of outpatient hysteroscopic tubal
      sterilization using a nitinol-dacron intratubal device without anaesthesia and to
      assess patient procedure compliance. MATERIALS AND METHODS: We untertook a
      prospective study of 36 consecutive cases of outpatient hysteroscopic tubal
      sterilization using a nitinol-dacron intratubal device without anaesthesia. Tubal
      sterilization was performed by placing the device with the aid of a 5.2-mm
      continuous-flow operative hysteroscope. At the end of the procedure women were
      asked to rate the pain experienced on a visual analogue scale (VAS) (0, no
      discomfort to 100, severe discomfort). Successful device placement was assessed
      after 3 months by hysterosalpingography and diagnostic hysteroscopy. RESULTS:
      Successful bilateral placement was obtained in 32 patients (88.9%); in one (2.8%)
      the placement was monolateral; and in three (8.3%) the procedure failed. Mean
      operating time was 8.6 +/- 5.3 min. A mean VAS of 36.1 +/- 23.9 was recorded.
      CONCLUSIONS: The nitinol-dacron intratubal device is safe, appears to be
      effective long-term, is non-invasive and can be used in the outpatient setting
      without anaesthesia. Low-level discomfort was experienced by the patients.
      Limitations of its use include that it is not effective immediately, it is
      irreversible, it requires special equipment and training, and it is difficult to
      use in cases of uterine anomalies. We conclude that this method may be offered to
      all woman asking for permanent tubal sterilization, particularly those who refuse
      or have contraindications for anaesthesia.

PMID- 16085665
TI  - Sperm DNA fragmentation: threshold value in male fertility.
AB  - BACKGROUND: The extent of sperm DNA fragmentation, which can be measured by the
      TUNEL assay, is one of the determinants of male fertility. However, the clinical
      application of this test to in-vivo situations is difficult owing to the absence
      of a statistically validated threshold value. METHODS: The aim of this study was
      to compare the results of TUNEL assay applied to semen samples from men of proven
      fertility (n = 47) and patients from an infertile population (n = 66), in order
      to establish a discriminating threshold value. RESULTS: Infertile patients had a
      higher mean level of DNA fragmentation than men of proven fertility (40.9 +/-
      14.3% versus 13.1 +/- 7.3%, respectively; P < 0.001). The area under the receiver
      operating characteristics curve was 0.93 for 20% sperm DNA fragmentation. The
      calculated threshold value for TUNEL assay to distinguish between fertile
      controls and infertile men was 20%. At this threshold, specificity was 89.4 [95%
      confidence interval (CI) 83.7-95.1] and sensitivity was 96.9% (95% CI 93.8-100).
      The positive and negative predictive values of the 20% sperm DNA fragmentation
      threshold were high: 92.8% (95% CI 87.9-97.5) and 95.5% (95% CI 91.6-99.3),
      respectively. CONCLUSION: This study demonstrates that sperm DNA fragmentation,
      as measured by TUNEL assay, is a highly valuable indicator of male fertility.

PMID- 16085666
TI  - Metabolic syndrome in young Czech women with polycystic ovary syndrome.
AB  - METHODS: Sixty-nine young women with polycystic ovary syndrome (PCOS) [age 25.2+/
      4.7 years, with body mass index (BMI) 24.3 +/- 4.8 kg/m2; mean 6 SD] and 73 age
      matched healthy females (BMI 22.3 +/- 3.3 kg/m2; mean +/- SD) were evaluated for
      the occurrence of features of metabolic syndrome according to the Adult Treatment
      Panel III. RESULTS: Overt metabolic syndrome (the presence of three and more risk
      factors) was not more common in PCOS women (1/64, 1.6%) than in healthy controls
      (0/73, 0%). On the other hand, in nearly 50% of PCOS women isolated features of
      metabolic syndrome, most often a decrease in high-density lipoprotein (HDL)
      cholesterol, were found. Women with at least one feature of metabolic syndrome
      were, in comparison with women without any of these features, significantly more
      obese (P = 0.0001), with lower insulin sensitivity (P = 0.05). When comparing
      PCOS women according to the degree of insulin sensitivity, as determined by
      euglycaemic clamp, isolated features of metabolic syndrome were found in 8/17
      women above the upper quartile, compared with 11/16 women below the lower
      quartile of insulin sensitivity (P = 0.20). CONCLUSIONS: Overt metabolic syndrome
      is only rarely encountered in young Czech females affected by PCOS but its
      isolated features are relatively frequent, both in young PCOS patients and in age
      matched control women.

PMID- 16085667
TI  - Effects of the insecticide amitraz, an alpha2-adrenergic receptor agonist, on
      human luteinized granulosa cells.
AB  - BACKGROUND: Amitraz, an insecticide used to prevent tick and mite infestation of
      cattle, crops and dogs, is an alpha2-adrenergic receptor agonist that inhibits
      GnRH release and the ovulatory LH surge in rats. Noradrenalin, the physiological
      ligand for adrenergic receptors, inhibits progesterone production by IVF-derived
      granulosa cells, but the effects of amitraz are unknown. METHODS: Luteinized
      granulosa cells obtained from women undergoing ovarian stimulation were exposed
      to amitraz (1, 10, 50, 100 microg/ml) for 2-72 h, and to amitraz (50 microg/ml)
      +/- hCG or the specific alpha2-adrenergic receptor antagonist yohimbine, for 6 h.
      Cell numbers were determined by 3-(4, 5-dimethylthiazol-(2)-yl)-2, 5-diphenyl
      tetrazolium bromide(MTT) assay and hormone production by radioimmunoassay.
      RESULTS: Amitraz 10 microg/ml did not affect cell numbers or estrogen production,
      but reduced progesterone production to 58 +/- 8% (p < 0.01, 24 h, n = 6) of
      control values. Amitraz (100 microg/ml) was cytotoxic and caused a corresponding
      reduction in hormone production. Amitraz 50 microg/ml did not affect cell numbers
      or estrogen production, but reduced progesterone per cell production to 82 +/- 6%
      of control values after 6 h. This was prevented by 0.2 mmol/l yohimbine. Exposure
      to amitraz 50 microg/ml for 6 h exposure abolished hCG-stimulated progesterone
      production but not estrogen production. CONCLUSIONS: Amitraz inhibited basal and
      hCG-stimulated progesterone but not estrogen production. The inhibitory action of
      amitraz and its antagonism by yohimbine suggest that alpha2-adrenergic receptors
      are expressed by luteinized human granulosa cells.

PMID- 16085669
TI  - The susceptibility to growth-promoting antibiotics of Enterococcus faecium
      isolates from pigs and chickens in Europe.
AB  - OBJECTIVES: To establish the susceptibility of Enterococcus faecium isolates from
      pigs and chickens to antimicrobial growth promoters that either were or had been
      in use in the European Union. METHODS: Samples were taken at abattoirs in two
      successive years (mid-1998-mid-1999, year 1; mid-1999-mid-2000, year 2) from
      chickens (France, The Netherlands, Sweden, UK) and pigs (Denmark, The
      Netherlands, Spain, Sweden). E. faecium was isolated from faecal samples at
      national laboratories and sent to a central laboratory where MICs of avilamycin,
      avoparcin, bacitracin, flavophospholipol, spiramycin, tylosin and virginiamycin
      were determined. Microbiological breakpoints were allocated on the basis of MIC
      distributions, and comparison was made between host species, country of origin
      and year of sample. RESULTS: In total, 2567 isolates were obtained from chickens
      and 1742 from pigs. In all countries, resistance to avoparcin (banned in 1997)
      was uncommon, but resistance to bacitracin and flavophospholipol was common (and
      was probably largely intrinsic). The prevalence of resistance was similar in
      chicken and pig isolates, with the exception of avilamycin, to which resistance
      was commoner among chicken isolates. The removal of four compounds as growth
      promoters (bacitracin, spiramycin, tylosin, virginiamycin) between years 1 and 2
      appeared to result in a significant decrease in resistance to three of them
      spiramycin, tylosin and virginiamycin, with no change in resistance to
      bacitracin, but an increase in resistance to avilamycin (not discontinued).
      Associated resistance was shown between some of the compounds. CONCLUSIONS:
      Resistance prevalence declined rapidly following removal of growth promoters in
      pigs and chickens, suggesting that in the absence of selective pressure, a
      susceptible population began to replace phenotypically resistant strains.
      Associated resistance between different compounds, where seen, could have
      resulted from either shared resistance mechanisms or from carriage of resistance
      genes on the same plasmid. Multiresistance to streptogramins, macrolides and
      glycopeptides was rare.

PMID- 16085670
TI  - Divergent contractile and structural responses of the murine PKC-epsilon null
      pulmonary circulation to chronic hypoxia.
AB  - Loss of PKC-epsilon limits the magnitude of acute hypoxic pulmonary
      vasoconstriction (HPV) in the mouse. Therefore, we hypothesized that loss of PKC
      epsilon would decrease the contractile and/or structural response of the murine
      pulmonary circulation to chronic hypoxia (Hx). However, the pattern of lung
      vascular responses to chronic Hx may or may not be predicted by the acute HPV
      response. Adult PKC-epsilon wild-type (PKC-epsilon(+/+)), heterozygous null, and
      homozygous null (PKC-epsilon(-/-)) mice were exposed to normoxia or Hx for 5 wk.
      PKC-epsilon(-/-) mice actually had a greater increase in right ventricular (RV)
      systolic pressure, RV mass, and hematocrit in response to chronic Hx than PKC
      epsilon(+/+) mice. In contrast to the augmented PA pressure and RV hypertrophy,
      pulmonary vascular remodeling was increased less than expected (i.e., equal to
      PKC-epsilon(+/+) mice) in both the proximal and distal PKC-epsilon(-/-) pulmonary
      vasculature. The contribution of increased vascular tone to this pulmonary
      hypertension (PHTN) was assessed by measuring the acute vasodilator response to
      nitric oxide (NO). Acute inhalation of NO reversed the increased PA pressure in
      hypoxic PKC-epsilon(-/-) mice, implying that the exaggerated PHTN may be due to a
      relative deficiency in nitric oxide synthase (NOS). Despite the higher PA
      pressure, chronic Hx stimulated less of an increase in lung endothelial (e) and
      inducible (i) NOS expression in PKC-epsilon(-/-) than PKC-epsilon(+/+) mice. In
      contrast, expression of nNOS in PKC-epsilon(+/+) mice decreased in response to
      chronic Hx, while lung levels in PKC-epsilon(-/-) mice remained unchanged. In
      summary, loss of PKC-epsilon results in increased vascular tone, but not
      pulmonary vascular remodeling in response to chronic Hx. Blunting of Hx-induced
      eNOS and iNOS expression may contribute to the increased vascular tone. PKC
      epsilon appears to be an important signaling intermediate in the hypoxic
      regulation of each NOS isoform.

PMID- 16085671
TI  - Oxytocin-induced labor augments IL-1beta-stimulated lung fluid absorption in
      fetal guinea pig lungs.
AB  - We tested the hypothesis that oxytocin-induced labor augmented IL-1beta-induced/
      stimulated lung fluid absorption in preterm guinea pig fetuses. IL-1beta was
      administered subcutaneously daily to timed-pregnant guinea pigs for 3 days with
      and without simultaneous cortisol synthesis inhibition by metyrapone. At day 3,
      oxytocin was administered, and fetuses were delivered by abdominal hysterotomy at
      61 and by oxytocin-induced birth at 68 days gestation. Delivered fetuses were
      instilled with isosmolar 5% albumin into the lungs, and lung fluid movement was
      measured over 1 h by mass balance. Lung fluid absorption was induced in 61-day
      and stimulated in 68-day gestation lungs by IL-1beta. Labor induction by oxytocin
      augmented IL-1beta-induced/-stimulated lung fluid absorption. Metyrapone
      pretreatment did not affect oxytocin-induced/-stimulated lung fluid absorption,
      while completely blocking IL-1beta-induced/-stimulated fluid absorption. Fetal
      lung fluid absorption, when present, was always propranolol and amiloride
      sensitive, suggesting that beta-adrenoceptor stimulation and amiloride-sensitive
      sodium channels were critical for fluid absorption. Epithelial sodium channel and
      Na-K-ATPase subunit expressions were both increased by IL-1beta, but not further
      by oxytocin. Our results indicate that IL-1beta release into the maternal blood
      circulation positively affects lung maturation due to the IL-1beta-induced
      release of cortisol and thus prepares the lungs for the epinephrine surge
      associated with labor.

PMID- 16085672
TI  - Hypoxic pulmonary hypertension: role of superoxide and NADPH oxidase (gp91phox).
AB  - Chronic exposure to low-O2 tension induces pulmonary arterial hypertension (PAH),
      which is characterized by vascular remodeling and enhanced vasoreactivity. Recent
      evidence suggests that reactive oxygen species (ROS) may be involved in both
      processes. In this study, we critically examine the role superoxide and NADPH
      oxidase plays in the development of chronic hypoxic PAH. Chronic hypoxia (CH; 10%
      O2 for 3 wk) caused a significant increase in superoxide production in
      intrapulmonary arteries (IPA) of wild-type (WT) mice as measured by lucigenin
      enhanced chemiluminescence. The CH-induced increase in the generation of ROS was
      obliterated in NADPH oxidase (gp91phox) knockout (KO) mice, suggesting that NADPH
      oxidase was the major source of ROS. Importantly, pathological changes associated
      with CH-induced PAH (mean right ventricular pressure, medial wall thickening of
      small pulmonary arteries, and right heart hypertrophy) were completely abolished
      in NADPH oxidase (gp91phox) KO mice. CH potentiated vasoconstrictor responses of
      isolated IPAs to both 5-hydroxytryptamine (5-HT) and the thromboxane mimetic U
      46619. Administration of CuZn superoxide dismutase to isolated IPA significantly
      reduced CH-enhanced superoxide levels and reduced the CH-enhanced
      vasoconstriction to 5-HT and U-46619. Additionally, CH-enhanced superoxide
      production and vasoconstrictor activity seen in WT IPAs were markedly reduced in
      IPAs isolated from NADPH oxidase (gp91phox) KO mice. These results demonstrate a
      pivotal role for gp91phox-dependent superoxide production in the pathogenesis of
      CH-induced PAH.

PMID- 16085673
TI  - Nitrogen dioxide enhances allergic airway inflammation and hyperresponsiveness in
      the mouse.
AB  - In addition to being an air pollutant, NO2 is a potent inflammatory oxidant
      generated endogenously by myeloperoxidase and eosinophil peroxidase. In these
      studies, we sought to determine the effects of NO2 exposure on mice with ongoing
      allergic airway disease pathology. Mice were sensitized and challenged with the
      antigen ovalbumin (OVA) to generate airway inflammation and subsequently exposed
      to 5 or 25 ppm NO2 for 3 days or 5 days followed by a 20-day recovery period.
      Whereas 5 ppm NO2 elicited no pathological changes, inhalation of 25 ppm NO2
      alone induced acute lung injury, which peaked after 3 days and was characterized
      by increases in protein, LDH, and neutrophils recovered by BAL, as well as
      lesions within terminal bronchioles. Importantly, 25 ppm NO2 was also sufficient
      to cause AHR in mice, a cardinal feature of asthma. The inflammatory changes were
      ameliorated after 5 days of inhalation and completely resolved after 20 days of
      recovery after the 5-day inhalation. In contrast, in mice immunized and
      challenged with OVA, inhalation of 25 ppm NO2 caused a marked augmentation of
      eosinophilic inflammation and terminal bronchiolar lesions, which extended
      significantly into the alveoli. Moreover, 20 days postcessation of the 5-day 25
      ppm NO2 inhalation regimen, eosinophilic and neutrophilic inflammation, pulmonary
      lesions, and AHR were still present in mice immunized and challenged with OVA.
      Collectively, these observations suggest an important role for NO2 in airway
      pathologies associated with asthma, both in modulation of degree and duration of
      inflammatory response, as well as in induction of AHR.

PMID- 16085674
TI  - Macrolide antibiotics modulate ERK phosphorylation and IL-8 and GM-CSF production
      by human bronchial epithelial cells.
AB  - Macrolide antibiotics decrease proinflammatory cytokine production in airway
      cells from subjects with chronic airway inflammation. However, in subjects with
      chronic obstructive pulmonary disease, short-term azithromycin (AZM) therapy
      causes a transient early increase in the blood neutrophil oxidative burst
      followed by a decrease in inflammatory markers with longer administration. We
      studied the effects of clarithromycin (CAM) and AZM on proinflammatory cytokine
      production from normal human bronchial epithelial (NHBE) cells. CAM decreased IL
      8 over the first 6 h and then significantly increased interleukin (IL)-8 at 12-72
      h after exposure (P < 0.0001). AZM also increased IL-8 at 24 and 48 h, and CAM
      increased granulocyte-macrophage colony-stimulating factor at 48 h. In the
      presence of LPS, both CAM and AZM dose-dependently increased IL-8 secretion over
      24 h, but after 5 days of exposure to 10 microg/ml CAM there is suppression of IL
      8 (P < 0.001). PD-98059, an inhibitor of MAP kinase/ERK kinase, inhibited CAM
      induced IL-8 (P < 0.0001) and GM-CSF (P < 0.01) release. The p38 MAP kinase
      inhibitor SB-203580 increased CAM-induced IL-8 release (P < 0.001), and the c-jun
      NH2-terminal kinase inhibitor SP-600125 had no effect on IL-8. At 120 min and 6
      h, CAM increased phospho-ERK1/2 (pERK) but not phospho-p38 or phospho-JNK. Over
      the first 90 min, CAM at 10 microg/ml inhibited pERK and then increased pERK in
      parallel with measured IL-8 secretion. After daily CAM exposure for 5 days, both
      IL-8 and pERK returned to baseline. The p38 MAP kinase inhibitor, SB-203580
      increased ERK phosphorylation and IL-8 secretion. These results suggest that
      macrolide antibiotics can differentially modulate proinflammatory cytokine
      secretion in NHBE cells, in part through ERK.

PMID- 16085675
TI  - Gene transfer of CFTR to airway epithelia: low levels of expression are
      sufficient to correct Cl- transport and overexpression can generate basolateral
      CFTR.
AB  - Gene transfer of CFTR cDNA to airway epithelia is a promising approach to treat
      cystic fibrosis (CF). Most gene transfer vectors use strong viral promoters even
      though the endogenous CFTR promoter is very weak. To learn whether expressing
      CFTR at a low level in a fraction of cells would correct Cl(-) transport, we
      mixed freshly isolated wild-type and CF airway epithelial cells in varying
      proportions and generated differentiated epithelia. Epithelia with approximately
      20% wild-type cells generated approximately 70% the transepithelial Cl(-) current
      of epithelia containing 100% wild-type cells. These data were nearly identical to
      those previously obtained with CFTR expressed under control of a strong promoter
      in a CF epithelial cell line. We also tested high level CFTR expression using the
      very strong cytomegalovirus (CMV) promoter as well as the cytokeratin-18 (K18)
      promoter. In differentiated airway epithelia, the CMV promoter generated 50-fold
      more transgene expression than the K18 promoter, but the K18 promoter generated
      more transepithelial Cl(-) current at high vector doses. Using functional
      studies, we found that with marked overexpression, some CFTR channels were
      present in the basolateral membrane where they shunted Cl(-) flow, thereby
      reducing net transepithelial Cl(-) transport. These results suggest that very
      little CFTR is required in a fraction of CF epithelial cells to complement Cl(-)
      transport because transepithelial Cl(-) flow is limited at the basolateral
      membrane. Thus they suggest a broad leeway in promoter strength for correcting
      the CF gene transfer, although at very high expression levels CFTR may be
      mislocalized to the basolateral membrane.

PMID- 16085676
TI  - Mechanism of sudden cardiac death in pigs with viable chronically dysfunctional
      myocardium and ischemic cardiomyopathy.
AB  - Pigs with viable chronically dysfunctional myocardium and ischemic cardiomyopathy
      are at high risk of sudden cardiac death (SCD). We sought to identify the
      arrhythmic mechanism of SCD, the relation to changes in left ventricular (LV)
      function, and inducibility of malignant arrhythmias before SCD. Juvenile pigs (n
      = 72) were instrumented with chronic stenoses on proximal left anterior
      descending and circumflex arteries. Survival was only 29% 3 mo after
      instrumentation, and all deaths were sudden and without prodromal symptoms of
      heart failure. Triphenyltetrazolium chloride staining demonstrated necrosis in
      only nine animals averaging 2.3 +/- 0.9% of the LV, with no difference between
      SCD animals and survivors. Implantable loop recorders (n = 13) documented both
      ventricular fibrillation (n = 6) and bradyasystole (n = 2) as the arrhythmic
      mechanism of death. Although regional and global function were depressed
      [anteroseptal wall thickening 1.8 +/- 0.2 vs. 4.2 +/- 0.2 mm in Sham animals (P <
      0.001); fractional shortening 21 +/- 2 vs. 31 +/- 1% in Sham animals (P < 0.01)],
      there were no differences between SCD animals and survivors. LV mass increased in
      animals with ischemic cardiomyopathy and was greater in animals with SCD (4.0 +/-
      0.2 vs. 3.1 +/- 0.1 g/kg in survivors; P < 0.001). Serial programmed ventricular
      stimulation failed to induce any sustained arrhythmias. We conclude that pigs
      with viable dysfunctional myocardium and globally reduced LV function have a high
      rate of SCD with a spectrum of arrhythmias similar to patients with ischemic
      cardiomyopathy. The risk is independent of necrosis but appears to increase with
      LV hypertrophy. Like patients with ischemic cardiomyopathy, programmed
      stimulation is insensitive to predict SCD when viable dysfunctional myocardium is
      the pathological substrate.

PMID- 16085677
TI  - Noninvasive three-dimensional electrocardiographic imaging of ventricular
      activation sequence.
AB  - Imaging the myocardial activation sequence is critical for improved diagnosis and
      treatment of life-threatening cardiac arrhythmias. It is desirable to reveal the
      underlying cardiac electrical activity throughout the three-dimensional (3-D)
      myocardium (rather than just the endocardial or epicardial surface) from
      noninvasive body surface potential measurements. A new 3-D electrocardiographic
      imaging technique (3-DEIT) based on the boundary element method (BEM) and
      multiobjective nonlinear optimization has been applied to reconstruct the cardiac
      activation sequences from body surface potential maps. Ultrafast computerized
      tomography scanning was performed for subsequent construction of the torso and
      heart models. Experimental studies were then conducted, during left and right
      ventricular pacing, in which noninvasive assessment of ventricular activation
      sequence by means of 3-DEIT was performed simultaneously with 3-D intracardiac
      mapping (up to 200 intramural sites) using specially designed plunge-needle
      electrodes in closed-chest rabbits. Estimated activation sequences from 3-DEIT
      were in good agreement with those constructed from simultaneously recorded
      intracardiac electrograms in the same animals. Averaged over 100 paced beats
      (from a total of 10 pacing sites), total activation times were comparable (53.3
      +/- 8.1 vs. 49.8 +/- 5.2 ms), the localization error of site of initiation of
      activation was 5.73 +/- 1.77 mm, and the relative error between the estimated and
      measured activation sequences was 0.32 +/- 0.06. The present experimental results
      demonstrate that the 3-D paced ventricular activation sequence can be
      reconstructed by using noninvasive multisite body surface electrocardiographic
      measurements and imaging of heart-torso geometry. This new 3-D
      electrocardiographic imaging modality has the potential to guide catheter-based
      ablative interventions for the treatment of life-threatening cardiac arrhythmias.

PMID- 16085678
TI  - Depressed cardiac myofilament function in human diabetes mellitus.
AB  - Diabetes mellitus is associated with a distinct cardiomyopathy. Whether cardiac
      myofilament function is altered in human diabetes mellitus is unknown. Myocardial
      biopsies were obtained from seven diabetic patients and five control, nondiabetic
      patients undergoing coronary artery bypass surgery. Myofilament function was
      assessed by determination of the developed force-Ca2+ concentration relation in
      skinned cardiac cells from flash-frozen human biopsies. Separate control
      experiments revealed that flash freezing of biopsy specimens did not affect
      myofilament function. All patients in the diabetes mellitus cohort were
      classified as Type 2 diabetes mellitus patients, and most showed signs of
      diastolic dysfunction. Diabetes mellitus was associated with depressed
      myofilament function, that is, decreased Ca2+ sensitivity (29%, P < 0.05 vs.
      control) and a trend toward reduction of maximum Ca2+-saturated force (29%, P =
      0.08 vs. control). The slope of the force-Ca2+ concentration relation (Hill
      coefficient) was not affected by diabetes, however. We conclude that human
      diabetes mellitus is associated with decreased cardiac myofilament function.
      Depressed cardiac myofilament Ca2+ responsiveness may underlie the decreased
      ventricular function characteristic of human diabetic cardiomyopathy.

PMID- 16085679
TI  - Measuring surface potential components necessary for transmembrane current
      computation using microfabricated arrays.
AB  - This study was designed to test the feasibility of using microfabricated
      electrodes to record surface potentials with sufficiently fine spatial resolution
      to measure the potential gradients necessary for improved computation of
      transmembrane current density. To assess that feasibility, we recorded unipolar
      electrograms from perfused rabbit right ventricular free wall epicardium (n = 6)
      using electrode arrays that included 25-microm sensors fabricated onto a flexible
      substrate with 75-microm interelectrode spacing. Electrode spacing was therefore
      on the size scale of an individual myocyte. Signal conditioning adjacent to the
      sensors to control lead noise was achieved by routing traces from the electrodes
      to the back side of the substrate where buffer amplifiers were located. For
      comparison, recordings were also made using arrays built from chloridized silver
      wire electrodes of either 50-microm (fine wire) or 250-microm (coarse wire)
      diameters. Electrode separations were necessarily wider than with microfabricated
      arrays. Comparable signal-to-noise ratios (SNRs) of 21.2 +/- 2.2, 32.5 +/- 4.1,
      and 22.9 +/- 0.7 for electrograms recorded using microfabricated sensors (n =
      78), fine wires (n = 78), and coarse wires (n = 78), respectively, were found.
      High SNRs were maintained in bipolar electrograms assembled using spatial
      combinations of the unipolar electrograms necessary for the potential gradient
      measurements and in second-difference electrograms assembled using spatial
      combinations of the bipolar electrograms necessary for surface Laplacian (SL)
      measurements. Simulations incorporating a bidomain representation of tissue
      structure and a two-dimensional network of guinea pig myocytes prescribed
      following the Luo and Rudy dynamic membrane equations were completed using 12.5
      microm spatial resolution to assess contributions of electrode spacing to the
      potential gradient and SL measurements. In those simulations, increases in
      electrode separation from 12.5 to 75.0, 237.5, and 875.0 microm, which were
      separations comparable to the finest available with our microfabricated, fine
      wire, and coarse wire arrays, led to 10%, 42%, and 81% reductions in maximum
      potential gradients and 33%, 76%, and 96% reductions in peak-to-peak SLs.
      Maintenance of comparable SNRs for source electrograms was therefore important
      because microfabrication provides a highly attractive methods to achieve spatial
      resolutions necessary for improved computation of transmembrane current density.

PMID- 16085680
TI  - Mechanisms of homocysteine-induced oxidative stress.
AB  - Hyperhomocysteinemia decreases vascular reactivity and is associated with
      cardiovascular morbidity and mortality. However, pathogenic mechanisms that
      increase oxidative stress by homocysteine (Hcy) are unsubstantiated. The aim of
      this study was to examine the molecular mechanism by which Hcy triggers oxidative
      stress and reduces bioavailability of nitric oxide (NO) in cardiac microvascular
      endothelial cells (MVEC). MVEC were cultured for 0-24 h with 0-100 microM Hcy.
      Differential expression of protease-activated receptors (PARs), thioredoxin,
      NADPH oxidase, endothelial NO synthase, inducible NO synthase, neuronal NO
      synthase, and dimethylarginine-dimethylaminohydrolase (DDAH) were measured by
      real-time quantitative RT-PCR. Reactive oxygen species were measured by using a
      fluorescent probe, 2',7'-dichlorofluorescein diacetate. Levels of asymmetric
      dimethylarginine (ADMA) were measured by ELISA and NO levels by the Griess method
      in the cultured MVEC. There were no alterations in the basal NO levels with 0-100
      microM Hcy and 0-24 h of treatment. However, Hcy significantly induced inducible
      NO synthase and decreased endothelial NO synthase without altering neuronal NO
      synthase levels. There was significant accumulation of ADMA, in part because of
      reduced DDAH expression by Hcy in MVEC. Nitrotyrosine expression was increased
      significantly by Hcy. The results suggest that Hcy activates PAR-4, which induces
      production of reactive oxygen species by increasing NADPH oxidase and decreasing
      thioredoxin expression and reduces NO bioavailability in cultured MVEC by 1)
      increasing NO2-tyrosine formation and 2) accumulating ADMA by decreasing DDAH
      expression.

PMID- 16085681
TI  - Is hemoglobin in hemoglobin vesicles infused for isovolemic hemodilution
      necessary to improve oxygenation in critically ischemic hamster skin?
AB  - The aim of this study was to test the influence of hemoglobin, encapsulated in
      phospholipid vesicles as an oxygen carrier, given in the course of isovolemic
      hemodilution to improve oxygenation in critically ischemic hamster flap tissue.
      Capillary hemodynamics and macromolecular leakage were investigated with
      intravital microscopy and analyzed off-line with the CapImage software. Partial
      tissue oxygen tension was measured with fluorescence quenching electrodes. The
      occurrence of apoptosis was assessed with the terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling assay. Vesicles with (HbV) or without
      (V) encapsulated Hb were suspended in 6% hydroxyethyl starch (HES) used for the
      33% blood exchange. In the ischemic tissue, hemodilution led to an increase in
      functional capillary density by 31% for HES (P < 0.01 vs. other groups), 66% for
      V-HES, and 62% for HbV-HES (all P < 0.01 vs. control). Capillary diameters
      behaved inversely proportional to capillary microhemodynamics. The 20% increase
      in macromolecular leakage found over time in control animals was completely
      abolished in the vesicles groups (P < 0.01) but not with HES. Oxygen tension was
      improved from 10.7 to 16.0 mmHg after HbV-HES (P < 0.01 vs. baseline and other
      groups). Compared with the other groups, apoptosis was significantly reduced
      after HbV-HES (P < 0.01). We conclude that the encapsulation of Hb was essential
      to attenuate hypoxia and subsequent cell death in the critically ischemic tissue.
      However, the effect was partly attributed to the rheological changes exerted by
      the vesicles.

PMID- 16085682
TI  - Maternal smoking during pregnancy and offspring IQ.
AB  - BACKGROUND: Maternal smoking in pregnancy lowers birthweight. It is unclear,
      however, whether smoking during pregnancy lowers offspring IQ, and, if it does,
      whether it is through the smoking effect on fetal growth. METHOD: Representative
      samples of low birthweight (<2500 g) and normal birthweight children born in 1983
      85 from inner-city and suburban communities in southeast Michigan, USA were
      assessed at ages 6, 11, and 17, using Wechsler intelligence tests. Smoking during
      pregnancy was ascertained from mothers at the first assessment; and smoking at
      any time was ascertained at the first and second assessment. Generalized
      estimating equation models were used, with children's IQ at all three assessments
      as outcomes (n = 798). RESULTS: Without adjustment, offspring of mothers who
      smoked during pregnancy scored 6.8 IQ points lower than offspring of mothers who
      never smoked, on average. Low birthweight children scored 5.4 IQ points lower
      than normal birthweight children, on average. The statistical association of
      maternal smoking with offspring IQ was confounded by maternal characteristics,
      chiefly, maternal cognitive ability as measured by IQ and education; adjustment
      for these factors eliminated the association. By contrast, adjustment for
      maternal IQ and education as well as smoking during pregnancy had a negligible
      effect on the low birthweight-related IQ deficit. Low birthweight did not mediate
      the association of smoking and lowered IQ in offspring. CONCLUSION: Maternal
      smoking during pregnancy is a proxy for a matrix of vulnerabilities for adverse
      child cognitive development and has no direct causal effect on child's IQ. The
      relationship of low birthweight and IQ is independent of maternal smoking and
      maternal cognitive abilities.

PMID- 16085685
TI  - Infant sleeping position and sudden infant death syndrome: a systematic review.

PMID- 16085686
TI  - Fatal haemothorax following large-bore percutaneous cannulation before liver
      transplantation.
AB  - Percutaneous bypass catheters are routinely used for veno-venous bypass (VVBP)
      during orthotopic liver transplantation (OLT). The recognized risks include
      bleeding, injury of vascular and nerve structures and lymphatic leakage. We
      describe a case where there were difficulties during catheterization and the
      patient suffered a cardiac arrest on commencing VVBP. Post-mortem examination
      revealed the bypass catheter tip in the pleural space and a large right
      haemothorax. Possible mechanisms of vascular perforation and preventative
      measures are discussed.

PMID- 16085687
TI  - Stereotactic radiosurgery for brain oligometastases: good for some, better for
      all?
AB  - Brain metastasis is the commonest central nervous system neoplasm affecting 25%
      patients with cancer. Recursive Partitioning Analysis (RPA) is a reliable
      prognostic index for patients with brain metastases. In patients with
      oligometastases and good performance status, decision-making regarding
      stereotactic radiosurgery (SRS) boost, following whole brain radiation therapy
      (WBRT), is guided by patient preference, access to radiosurgical facility and
      institutional policy. Published data for this review was identified by a
      systematic search of MEDLINE, CANCERLIT and EMBASE databases from 1990 until the
      present date and was restricted to the English language using appropriate search
      terms. All three identified randomized controlled trials consistently showed that
      radiosurgery improves intracranial local control (Level I evidence). Survival
      benefit, however, is limited to a selected subset of patients (RPA class 1) only.
      More importantly, patients receiving SRS have significantly better performance
      scores and decreased steroid requirements resulting in improved health-related
      quality-of-life (HRQoL). There is no head-to-head comparison of radiosurgery with
      neurosurgery in resectable single metastasis. SRS is associated with an
      improvement in outcome. A trial of radiosurgery versus neurosurgery should be
      attempted to define better the role of SRS in resectable single metastasis.
      Formal HRQoL assessments should be incorporated as primary end points in future
      prospective trials.

PMID- 16085688
TI  - Cancer and aging: are there any differences in the information needs of elderly
      and younger patients? Results from an Italian observational study.

PMID- 16085689
TI  - Hormone receptors do not predict the HER2/neu status in all age groups of women
      with an operable breast cancer.
AB  - BACKGROUND: In breast cancer, there is an inverse relationship between HER2/neu
      overexpression and receptors for estrogen (ER) or progesterone (PR). Some
      clinical observations such as the age-related association between hormone
      receptors and tumour grade, which predicts HER2/neu overexpression, suggest an
      age-related relationship. PATIENTS AND METHODS: Our study population consisted of
      1362 consecutive women receiving primary surgery for non-metastatic invasive
      breast cancer. We compared the relationship between both hormone receptors and
      HER2/neu overexpression in different age groups taking other tumour
      characteristics into account. RESULTS: In a multivariate model, considering the
      overall group, a negative ER, a negative PR and a high tumour grade were
      predictive for HER2/neu overexpression (P <0.001). Considering 246 women aged <
      or =45 years, the only predictor for HER2/neu overexpression in this age category
      was a high tumour grade (P = 0.003). Considering the 1116 women aged >45 years,
      ER (P = 0.001), PR (P = 0.001) and tumour grade (P <0.001) were associated with
      HER2/neu (P <0.001). CONCLUSION: Our findings indicate that the association
      between ER, PR and HER2/neu overexpression varies with age. The hormone receptors
      are not an independent predictor for the HER2/neu status in young women while
      they are in elder patients.

PMID- 16085690
TI  - Increased risk of esophageal cancer after breast cancer.
AB  - BACKGROUND: Adjuvant radiation therapy for breast cancer has been related to
      excess esophageal cancer risk, but population-based data are scanty. PATIENTS AND
      METHODS: We considered esophageal cancer risk among 11 130 breast cancer patients
      diagnosed between 1974 and 2002 in the Swiss cantons of Vaud and Neuchatel, and
      followed-up to the end of 2002, for a total of 75 900 women-years at risk.
      RESULTS: Overall, 18 cases were observed compared with 8.9 expected,
      corresponding to a standardised incidence ratio (SIR) of 2.0 [95% confidence
      interval (CI) 1.2-3.2]. The SIR was 1.6 in the first 10 years after diagnosis and
      3.3 for >/=10 years after diagnosis, 2.3 for cases diagnosed between 1974 and
      1988 and 1.5 for those diagnosed after 1988, 2.3 (based on 15 cases) for squamous
      cell cancer and 1.3 (based on three cases) for adenocarcinomas, and 2.9 for the
      upper third, 2.3 for the middle third and 1.9 for the lower third of the
      esophagus. CONCLUSIONS: These data confirm an excess esophageal cancer risk
      following treatment for breast cancer which could not be explained by confounding
      of tobacco or alcohol alone. The excess risk tended to decrease for cases
      diagnosed after 1988, leaving open the issue of the risk of modern radiotherapy
      for breast cancer on esophageal cancer.

PMID- 16085691
TI  - Endocrine pancreatic tumors: factors correlated with survival.
AB  - BACKGROUND: The aim of this study was to evaluate the survival rate of patients
      with endocrine tumors of the pancreas, functioning or non-functioning, associated
      or not with MEN 1 syndrome. PATIENTS AND METHODS: Eighty-three patients with
      pancreatic endocrine tumors diagnosed in our department from 1978 to 2003 were
      studied. RESULTS: The study included 37 men (44.6%) and 46 women (55.4%). The
      median age of patients at diagnosis was 55 years (range 19-81 years). Fifty-two
      patients (62.7%) had non-functioning endocrine tumors, 16 (19.3%) had functioning
      endocrine tumors and 15 (18.1%) had MEN 1 disease with pancreatic involvement.
      Twenty-seven patients (32.5%) had liver metastases at the time of diagnosis,
      involvement of the lymph nodes was found in 47 out of 79 patients (59.5%). Forty
      patients (48.2%) had radical surgery, 20 (24.1%) had palliative surgery and 53
      were treated medically. The survival rate was significantly related to the
      presence of metastases, lymph node involvement, and the type of tumor and
      treatment. CONCLUSIONS: Tumor resection, the absence of liver and lymph node
      metastases, and the presence of MEN 1 syndrome are related to a better survival
      rate. Radical surgery continues to have a central role in the therapeutic
      approach to endocrine tumors of the pancreas.

PMID- 16085692
TI  - PS-341 and gemcitabine in patients with metastatic pancreatic adenocarcinoma: a
      North Central Cancer Treatment Group (NCCTG) randomized phase II study.
AB  - BACKGROUND: PS-341 is a proteasome inhibitor with preclinical activity in
      pancreatic cancer tumor models and synergistic activity with gemcitabine. This
      randomized phase II study determined the tumor response rate (RR) for PS-341
      alone and the 6-month survival and RR for the combination of gemcitabine and PS
      341 in patients with metastatic pancreatic adenocarcinoma. PATIENTS AND METHODS:
      Patients were randomized to receive 3-week cycles of either arm A: PS-341 1.5
      mg/m(2) i.v. bolus (over 3--5 s) on days 1, 4, 8 and 11 or arm B: PS-341 1.0
      mg/m(2) (same as arm A otherwise) plus gemcitabine 1,000 mg/m(2) i.v. on days 1
      and 8. Patients progressing on arm A were allowed to receive arm B treatment.
      RESULTS: Arm A: 42 evaluable patients were enrolled with a confirmed RR of 0%
      (95% CI 0% to 8%), median survival of 2.5 months (95% CI 2.0-3.3), and median
      time to progression (TTP) of 1.2 months (95% CI 1.1--1.3). Twelve of 43 evaluable
      patients (28%) experienced at least one grade 4+ AE. Arm B: 39 evaluable patients
      yielded a 6-month survival rate of 41% (16/39, 95% CI 29.8% to 67.0%), median
      survival of 4.8 months (95% CI 2.4--7.4), median TTP of 2.4 months (95% CI 1.5-
      3.1), and confirmed RR of 10% (4 partial responses/0 complete responses, 95% CI
      3% to 24%). Eleven of 43 evaluable patients (26%) experienced at least one grade
      4+ AE. One patient had grade 5 hypotension. CONCLUSION: The use of PS-341 alone
      or in combination with gemcitabine did not result in an overall survival and RR
      better than that expected for gemcitabine alone. Based on the lack of efficacy
      and the toxicity seen in our trial, there does not appear to be a role for PS-341
      in pancreatic adenocarcinoma with either of the schedules used in this trial.

PMID- 16085693
TI  - Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind,
      placebo controlled, crossover study.
AB  - BACKGROUND: Diabetic gastroparesis is a disabling condition with no consistently
      effective treatment. In animals, ghrelin increases gastric emptying and reverses
      postoperative ileus. We present the results of a double blind, placebo
      controlled, crossover study of ghrelin in gastric emptying in patients with
      diabetic gastroparesis. METHODS: Ten insulin requiring diabetic patients (five
      men, six type I) referred with symptoms indicative of gastroparesis received a
      two hour infusion of either ghrelin (5 pmol/kg/min) or saline on two occasions.
      Blood glucose was controlled by euglycaemic clamp. Gastric emptying rate (GER)
      was calculated by real time ultrasound following a test meal. Blood was sampled
      for ghrelin, growth hormone (GH), and pancreatic polypeptide (PP) levels.
      Cardiovagal neuropathy was assessed using the Mayo Clinic composite autonomic
      severity score (range 0 (normal)-3). RESULTS: Baseline ghrelin levels were mean
      445 (SEM 36) pmol/l. Ghrelin infusion achieved a peak plasma level of 2786 (188)
      pmol/l at 90 minutes, corresponding to a peak GH of 70.9 (19.8) pmol/l. Ghrelin
      increased gastric emptying in seven of 10 patients (30 (6)% to 43 (5)%; p =
      0.04). Impaired cardiovagal tone correlated inversely with peak postprandial PP
      values (p < 0.05) but did not correlate with GER. CONCLUSIONS: Ghrelin increases
      gastric emptying in patients with diabetic gastroparesis. This is independent of
      vagal tone. We propose that analogues of ghrelin may represent a new class of
      prokinetic agents.

PMID- 16085694
TI  - Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in
      colonic adenoma.
AB  - BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) expression in subepithelial
      macrophages of colorectal adenoma has been suggested as the first in a series of
      steps leading to colorectal tumorigenesis. We tested the hypothesis that
      chemokines released from human colorectal adenoma epithelium might be involved in
      COX-2 expression in macrophages of the lamina propria. METHODS: Endoscopic
      samples of sporadic colorectal adenomas were tested by enzyme linked
      immunosorbent assay for chemokines involved in macrophage chemotaxis.
      Localisation of adenoma macrophage chemoattractant protein 1 (MCP-1) and COX-2
      were determined by immunohistochemistry. The effects of MCP-1, in the presence or
      absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E(2) and
      vascular endothelial growth factor (VEGF) release, were examined in human
      macrophages isolated from peripheral blood. RESULTS: MCP-1 levels were markedly
      higher in adenoma with mild-moderate dysplasia (129.7 (19.9) pg/mg protein) and
      severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8
      (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins
      (MIP)-1alpha and MIP-1beta, and the chemokine regulated on activation of normal T
      cell expressed and secreted (RANTES) did not vary significantly between adenoma
      and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa
      increased significantly three hours after tissue cultivation in vitro. MCP-1
      immunoreactivity was restricted to the adenoma epithelium, with no reactivity
      seen in adjacent normal epithelial cells. MCP-1 stimulated COX-2 expression and
      PGE(2) and VEGF release in human macrophages. Celecoxib, a selective COX-2
      inhibitor, inhibited MCP-1-induced PGE(2) and VEGF release in macrophages.
      Addition of exogenous PGE(2) reversed this inhibitory effect on VEGF release,
      suggesting that MCP-1 in adenoma epithelial cells might be involved in COX-2
      expression and subsequent macrophage activation. CONCLUSIONS: MCP-1 in colorectal
      adenoma epithelial cells might be involved in macrophage migration and COX-2
      expression, leading to the subsequent development of colonic adenoma.

PMID- 16085695
TI  - Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene.
AB  - BACKGROUND: Cutis laxa is an acquired or inherited condition characterized by
      redundant, pendulous and inelastic skin. Autosomal dominant cutis laxa has been
      described as a benign disease with minor systemic involvement. OBJECTIVE: To
      report a family with autosomal dominant cutis laxa and a young girl with sporadic
      cutis laxa, both with variable expression of an aortic aneurysmal phenotype
      ranging from mild dilatation to severe aneurysm or aortic rupture. METHODS AND
      RESULTS: Histological evaluation of aortic aneurysmal specimens indicated
      classical hallmarks of medial degeneration, paucity of elastic fibres, and an
      absence of inflammatory or atherosclerotic lesions. Electron microscopy showed
      extracellular elastin deposits lacking microfibrillar elements. Direct sequencing
      of genomic amplimers detected defects in exon 30 of the elastin gene in affected
      individuals, but did not in 121 normal controls. The expression of mutant elastin
      mRNA forms was demonstrated by reverse transcriptase polymerase chain reaction
      analysis of cutis laxa fibroblasts. These mRNAs coded for multiple mutant
      tropoelastins, including C-terminally truncated and extended forms as well as for
      molecules lacking the constitutive exon 30. CONCLUSIONS: ELN mutations may cause
      severe aortic disease in patients with cutis laxa. Thus regular cardiac
      monitoring is necessary in this disease to avert fatal aortic rupture.

PMID- 16085696
TI  - Quantitative trait locus (QTL) isogenic recombinant analysis: a method for high
      resolution mapping of QTL within a single population.
AB  - In the quest for fine mapping quantitative trait loci (QTL) at a subcentimorgan
      scale, several methods that involve the construction of inbred lines and the
      generation of large progenies of such inbred lines have been developed (Complex
      Trait Consortium 2003). Here we present an alternative method that significantly
      speeds up QTL fine mapping by using one segregating population. As a first step,
      a rough mapping analysis is performed on a small part of the population. Once the
      QTL have been mapped to a chromosomal interval by standard procedures, a large
      population of 1000 plants or more is analyzed with markers flanking the defined
      QTL to select QTL isogenic recombinants (QIRs). QIRs bear a recombination event
      in the QTL interval of interest, while other QTL have the same homozygous
      genotype. Only these QIRs are subsequently phenotyped to fine map the QTL. By
      focusing at an early stage on the informative individuals in the population only,
      the efforts in population genotyping and phenotyping are significantly reduced as
      compared to prior methods. The principles of this approach are demonstrated by
      fine mapping an erucic acid QTL of rapeseed at a subcentimorgan scale.

PMID- 16085697
TI  - Genetic evidence that Drosophila frizzled controls planar cell polarity and
      Armadillo signaling by a common mechanism.
AB  - The frizzled (fz) gene in Drosophila controls two distinct signaling pathways: it
      directs the planar cell polarization (PCP) of epithelia and it regulates cell
      fate decisions through Armadillo (Arm) by acting as a receptor for the Wnt
      protein Wingless (Wg). With the exception of dishevelled (dsh), the genes
      functioning in these two pathways are distinct. We have taken a genetic approach,
      based on a series of new and existing fz alleles, for identifying individual
      amino acids required for PCP or Arm signaling. For each allele, we have attempted
      to quantify the strength of signaling by phenotypic measurements. For PCP
      signaling, the defect was measured by counting the number of cells secreting
      multiple hairs in the wing. We then examined each allele for its ability to
      participate in Arm signaling by the rescue of fz mutant embryos with maternally
      provided fz function. For both PCP and Arm signaling we observed a broad range of
      phenotypes, but for every allele there is a strong correlation between its
      phenotypic strength in each pathway. Therefore, even though the PCP and Arm
      signaling pathways are genetically distinct, the set of signaling-defective fz
      alleles affected both pathways to a similar extent. This suggests that fz
      controls these two different signaling activities by a common mechanism. In
      addition, this screen yielded a set of missense mutations that identify amino
      acids specifically required for fz signaling function.

PMID- 16085699
TI  - The gene doublesex of the fruit fly Anastrepha obliqua (Diptera, Tephritidae).
AB  - The gene doublesex of Anastrepha obliqua is composed of four instead of the usual
      six exons. It is transcribed in both sexes and its primary transcript undergoes
      sex-specific splicing, producing female Dsx(F) and male Dsx(M) proteins, which
      have in common the amino-terminal region but which differ at the carboxyl
      terminal region.

PMID- 16085698
TI  - Insertional polymorphism and antiquity of PDR1 retrotransposon insertions in
      pisum species.
AB  - Sequences flanking 73 insertions of the retrotransposon PDR1 have been
      characterized, together with an additional 270 flanking regions from one side
      alone, from a diverse collection of Pisum germ plasm. Most of the identified
      flanking sequences are repetitious DNAs but more than expected (7%) lie within
      nuclear gene protein-coding regions. The approximate age of 52 of the PDR1
      insertions has been determined by measuring sequence divergence among LTR pairs.
      These data show that PDR1 transpositions occurred within the last 5 MY, with a
      peak at 1-2.5 MYA. The insertional polymorphism of 68 insertions has been
      assessed across 47 selected Pisum accessions, representing the diversity of the
      genus. None of the insertions are fixed, showing that PDR1 insertions can persist
      in a polymorphic state for millions of years in Pisum. The insertional
      polymorphism data have been compared with the age estimations to ask what rules
      control the proliferation of PDR1 insertions in Pisum. Relatively recent
      insertions (< approximately 1.5 MYA) tend to be found in small subsets of the
      Pisum accessions set, "middle-aged" insertions (between approximately 1.5 and 2.5
      MYA) vary greatly in their occurrence, and older insertions (> approximately 2.5
      MYA) are mostly found in small subsets of Pisum. Finally, the average age
      estimate for PDR1 insertions, together with an existing data set for PDR1
      retrotransposon SSAP markers, has been used to derive an estimate of the
      effective population size for Pisum of approximately 7.5 x 10(5).

PMID- 16085700
TI  - Bias and precision in QST estimates: problems and some solutions.
AB  - Comparison of population differentiation in neutral marker genes and in genes
      coding quantitative traits by means of F(ST) and Q(ST) indexes has become
      commonplace practice. While the properties and estimation of F(ST) have been the
      subject of much interest, little is known about the precision and possible bias
      in Q(ST) estimates. Using both simulated and real data, we investigated the
      precision and bias in Q(ST) estimates and various methods of estimating the
      precision. We found that precision of Q(ST) estimates for typical data sets
      (i.e., with <20 populations) was poor. Of the methods for estimating the
      precision, a simulation method, a parametric bootstrap, and the Bayesian approach
      returned the most precise estimates of the confidence intervals.

PMID- 16085701
TI  - The relationship of nucleotide polymorphism, recombination rate and selection in
      wild tomato species.
AB  - We analyzed the effects of mating system and recombination rate on single
      nucleotide polymorphisms using 14 single-copy nuclear loci from single
      populations of five species of wild tomatoes (Solanum section Lycopersicon). The
      taxa investigated comprise two self-compatible (SC) and three self-incompatible
      (SI) species. The observed reduction in nucleotide diversity in the SC
      populations compared to the SI populations is much stronger than expected under
      the neutral effects of the mating system on effective population size.
      Importantly, outgroup sequences available for 11 of the 14 loci yield strong
      positive correlations between silent nucleotide diversity and silent divergence,
      indicative of marked among-locus differences in mutation rates and/or selective
      constraints. Furthermore, using a physical estimate of local recombination rates,
      we find that silent nucleotide diversity (but not divergence) is positively
      correlated with recombination rate in two of the SI species. However, this
      correlation is not nearly as strong as in other well-characterized species (in
      particular, Drosophila). We propose that nucleotide diversity in Lycopersicon is
      dominated mainly by differences in neutral mutation rates and/or selective
      constraints among loci, demographic processes (such as population subdivision),
      and background selection. In addition, we hypothesize that the soil seed bank
      plays an important role in the maintenance of the large genetic diversity in the
      SI species (in particular L. peruvianum).

PMID- 16085703
TI  - Maximum-likelihood estimation of coalescence times in genealogical trees.
AB  - We develop a method for maximum-likelihood estimation of coalescence times in
      genealogical trees, based on population genetics data. For this purpose, a
      Viterbi-type algorithm is constructed to maximize the joint likelihood of the
      coalescence times. Marginal confidence intervals for the coalescence times based
      on the profile likelihoods are also computed. Our method of finding MLEs and
      calculating C.I.'s appears to be more accurate than alternative numerical
      maximization methods, and maximum-likelihood inference appears to be more
      accurate than other existing model-free approaches to estimating coalescent
      times. We demonstrate the method on two different data sets: human Y chromosome
      DNA data and fungus DNA data.

PMID- 16085705
TI  - Polymorphisms in cinnamoyl CoA reductase (CCR) are associated with variation in
      microfibril angle in Eucalyptus spp.
AB  - Linkage disequilibrium (LD) mapping using natural populations results in higher
      resolution of marker-trait associations compared to family-based quantitative
      trait locus (QTL) studies. Depending on the extent of LD, it is possible to
      identify alleles within candidate genes associated with a trait. Analysis of a
      natural mutant in Arabidopsis has shown that mutations in cinnamoyl CoA reductase
      (CCR), a key lignin gene, affect physical properties of the secondary cell wall
      such as stiffness and strength. Using this gene, we tested whether LD mapping
      could identify alleles associated with microfibril angle (MFA), a wood quality
      trait affecting stiffness and strength of wood. We identified 25 common single
      nucleotide polymorphism (SNP) markers in the CCR gene in Eucalyptus nitens. Using
      single-marker and haplotype analyses in 290 trees from a E. nitens natural
      population, two haplotypes significantly associated with MFA were found. These
      results were confirmed in two full-sib families of E. nitens and Eucalyptus
      globulus. In an effort to understand the functional significance of the SNP
      markers, we sequenced the cDNA clones and identified an alternatively spliced
      variant from the significant haplotype region. This study demonstrates that LD
      mapping can be used to identify alleles associated with wood quality traits in
      natural populations of trees.

PMID- 16085704
TI  - Mcm10 is required for the maintenance of transcriptional silencing in
      Saccharomyces cerevisiae.
AB  - Mcm10 is an essential protein that participates in both the initiation and the
      elongation of DNA replication. In this study we demonstrate a role for Mcm10 in
      the maintenance of heterochromatic silencing at telomeres and HM loci of budding
      yeast. Two mcm10 mutants drastically reduce silencing of both URA3 and ADE2
      reporter genes integrated into these silent loci. When exposed to alpha-factor,
      mcm10 mutant cells display a "shmoo-cluster" phenotype associated with a defect
      in the maintenance of silencing. In addition, when combined with a defect in the
      establishment of silent chromatin, mcm10 mutants demonstrate a synergistic defect
      in HML silencing. Consistent with a direct silencing function, Mcm10p shows a two
      hybrid interaction with Sir2p and Sir3p that is destroyed by the mcm10-1 mutation
      and dependent on the C-terminal 108 amino acids. Tethering GBD-MCM10 to a
      defective HMR-E silencer is not sufficient to restore silencing. Furthermore,
      mutations in MCM10 inhibit the ability of GBD-SIR3 to restore silencing when
      tethered to a defective HMR-E. Suppressor mutations in MCM2, which suppress the
      temperature sensitivity of mcm10-1, fail to overcome the mcm10-1 silencing
      defect, suggesting that MCM10's role in transcriptional silencing may be separate
      from its essential functions in DNA replication.

PMID- 16085706
TI  - Using progenitor strain information to identify quantitative trait nucleotides in
      outbred mice.
AB  - We have developed a fast and economical strategy for dissecting the genetic
      architecture of quantitative trait loci at a molecular level. The method uses two
      pieces of information: mapping data from crosses that involve more than two
      inbred strains and sequence variants in the progenitor strains within the
      interval containing a quantitative trait locus (QTL). By testing whether the
      strain distribution pattern in the progenitor strains is consistent with the
      observed genetic effect of the QTL we can assign a probability that any sequence
      variant is a quantitative trait nucleotide (QTN). It is not necessary to genotype
      the animals except at a skeleton of markers; the genotypes at all other
      polymorphisms are estimated by a multipoint analysis. We apply the method to a
      4.8-Mb region on mouse chromosome 1 that contains a QTL influencing anxiety
      segregating in a heterogeneous stock and show that, under the assumption that a
      single QTN is present and lies in a region conserved between the human and mouse
      genomes, it is possible to reduce the number of variants likely to be the
      quantitative trait nucleotide from many thousands to <20.

PMID- 16085702
TI  - Molecular population genetics of accessory gland protein genes and testis
      expressed genes in Drosophila mojavensis and D. arizonae.
AB  - Molecular population genetic investigation of Drosophila male reproductive genes
      has focused primarily on melanogaster subgroup accessory gland protein genes
      (Acp's). Consistent with observations from male reproductive genes of numerous
      taxa, Acp's evolve more rapidly than nonreproductive genes. However, within the
      Drosophila genus, large data sets from additional types of male reproductive
      genes and from different species groups are lacking. Here we report findings from
      a molecular population genetics analysis of male reproductive genes of the
      repleta group species, Drosophila arizonae and D. mojavensis. We find that Acp's
      have dramatically higher average pairwise Ka/Ks (0.93) than testis-enriched genes
      (0.19) and previously reported melanogaster subgroup Acp's (0.42). Overall, 10 of
      19 Acp's have Ka/Ks > 1 either in nonpolarized analyses or in at least one
      lineage of polarized analyses. Of the nine Acp's for which outgroup data were
      available, average Ka/Ks was considerably higher in D. mojavensis (2.08) than in
      D. arizonae (0.87). Contrasts of polymorphism and divergence suggest that
      adaptive protein evolution at Acp's is more common in D. mojavensis than in D.
      arizonae.

PMID- 16085707
TI  - Unusual compactness of a polyproline type II structure.
AB  - Polyproline type II (PPII) helix has emerged recently as the dominant paradigm
      for describing the conformation of unfolded polypeptides. However, most
      experimental observables used to characterize unfolded proteins typically provide
      only short-range, sequence-local structural information that is both time- and
      ensemble-averaged, giving limited detail about the long-range structure of the
      chain. Here, we report a study of a long-range property: the radius of gyration
      of an alanine-based peptide, Ace-(diaminobutyric acid)2-(Ala)7-(ornithine)2-NH2.
      This molecule has previously been studied as a model for the unfolded state of
      proteins under folding conditions and is believed to adopt a PPII fold based on
      short-range techniques such as NMR and CD. By using synchrotron radiation and
      small-angle x-ray scattering, we have determined the radius of gyration of this
      peptide to be 7.4 +/- 0.5 angstroms, which is significantly less than the value
      expected from an ideal PPII helix in solution (13.1 angstroms). To further study
      this contradiction, we have used molecular dynamics simulations using six
      variants of the AMBER force field and the GROMOS 53A6 force field. However, in
      all cases, the simulated ensembles underestimate the PPII content while
      overestimating the experimental radius of gyration. The conformational model that
      we propose, based on our small angle x-ray scattering results and what is known
      about this molecule from before, is that of a very flexible, fluctuating
      structure that on the level of individual residues explores a wide basin around
      the ideal PPII geometry but is never, or only rarely, in the ideal extended PPII
      helical conformation.

PMID- 16085708
TI  - A genome-wide transcriptional analysis using Arabidopsis thaliana Affymetrix gene
      chips determined plant responses to phosphate deprivation.
AB  - Phosphorus, one of the essential elements for plants, is often a limiting
      nutrient because of its low availability and mobility in soils. Significant
      changes in plant morphology and biochemical processes are associated with
      phosphate (Pi) deficiency. However, the molecular bases of these responses to Pi
      deficiency are not thoroughly elucidated. Therefore, a comprehensive survey of
      global gene expression in response to Pi deprivation was done by using
      Arabidopsis thaliana whole genome Affymetrix gene chip (ATH1) to quantify the
      spatio-temporal variations in transcript abundance of 22,810 genes. The analysis
      revealed a coordinated induction and suppression of 612 and 254 Pi-responsive
      genes, respectively. The functional classification of some of these genes
      indicated their involvement in various metabolic pathways, ion transport, signal
      transduction, transcriptional regulation, and other processes related to growth
      and development. This study is a detailed analysis of Pi starvation-induced
      changes in gene expression of the entire genome of Arabidopsis correlated with
      biochemical processes. The results not only enhance our knowledge about molecular
      processes associated with Pi deficiency, but also facilitate the identification
      of key molecular determinants for improving Pi use by crop species.

PMID- 16085709
TI  - Ligand migration pathway and protein dynamics in myoglobin: a time-resolved
      crystallographic study on L29W MbCO.
AB  - By using time-resolved x-ray crystallography at room temperature, structural
      relaxations and ligand migration were examined in myoglobin (Mb) mutant L29W from
      nanoseconds to seconds after photodissociation of carbon monoxide (CO) from the
      heme iron by nanosecond laser pulses. The data were analyzed in terms of
      transient kinetics by fitting trial functions to integrated difference electron
      density values obtained from select structural moieties, thus allowing a
      quantitative description of the processes involved. The observed relaxations are
      linked to other investigations on protein dynamics. At the earliest times, the
      heme has already completely relaxed into its domed deoxy structure, and there is
      no photo-dissociated CO visible at the primary docking site. Initial relaxations
      of larger globin moieties are completed within several hundred nanoseconds. They
      influence the concomitant migration of photo-dissociated CO to the Xe1 site,
      where it appears at approximately 300 ns and leaves again at approximately 1.5
      ms. The extremely long residence time in Xe1 as compared with wild-type MbCO
      implies that, in the latter protein, the CO exits the protein from Xe1
      predominantly via the distal pocket. A well-defined deligated state is populated
      between approximately 2 micros and approximately 1 ms; its structure is very
      similar to the equilibrium deoxy structure. Between 1.5 and 20 ms, no CO is
      visible in the protein interior; it is either distributed among many sites within
      the protein or has escaped to the solvent. Finally, recombination at the heme
      iron occurs after >20 ms.

PMID- 16085710
TI  - Blood-testis barrier dynamics are regulated by an engagement/disengagement
      mechanism between tight and adherens junctions via peripheral adaptors.
AB  - In the mammalian testis, the blood-testis barrier (BTB), unlike the blood-brain
      and blood-retina barriers, is composed of coexisting tight junctions (TJs) and
      adherens junctions (AJs). Yet these junctions must open (or disassemble) to
      accommodate the migration of preleptotene and leptotene spermatocytes across the
      BTB during spermatogenesis while maintaining its integrity. In this report, we
      show that the BTB utilizes a unique "engagement" and "disengagement" mechanism to
      permit the disruption of AJ that facilitates germ cell movement without
      compromising the BTB integrity. For instance, both TJ (e.g., occludin and JAM-1)
      and AJ (e.g., N-cadherin) integral membrane proteins were colocalized to the same
      site at the BTB. Although these TJ- and AJ-integral membrane proteins did not
      physically interact with each other, they were structurally linked by means of
      peripheral adaptors (e.g., ZO-1 and alpha- and gamma-catenins). As such, these
      proteins are structurally "engaged" under physiological conditions to reinforce
      the BTB. When rats were exposed to Adjudin to induce AJ restructuring that
      eventually led to germ cell loss from the epithelium, this structural interaction
      between occludin and N-cadherin by means of their adaptors became "disengaged"
      while their protein levels were significantly induced. In short, when the
      epithelium is under assault, such as by Adjudin or plausibly at the time of germ
      cell migration across the BTB during spermatogenesis, the TJ- and AJ-integral
      membrane proteins can be disengaged. Thus, this mechanism is used by the testis
      to facilitate AJ restructuring to accommodate germ cell migration while
      maintaining the BTB integrity.

PMID- 16085711
TI  - Asynchronous extinction of late Quaternary sloths on continents and islands.
AB  - Whatever the cause, it is extraordinary that dozens of genera of large mammals
      became extinct during the late Quaternary throughout the Western Hemisphere,
      including 90% of the genera of the xenarthran suborder Phyllophaga (sloths).
      Radiocarbon dates directly on dung, bones, or other tissue of extinct sloths
      place their "last appearance" datum at approximately 11,000 radiocarbon years
      before present (yr BP) or slightly less in North America, approximately 10,500 yr
      BP in South America, and approximately 4,400 yr BP on West Indian islands. This
      asynchronous situation is not compatible with glacial-interglacial climate change
      forcing these extinctions, especially given the great elevational, latitudinal,
      and longitudinal variation of the sloth-bearing continental sites. Instead, the
      chronology of last appearance of extinct sloths, whether on continents or
      islands, more closely tracks the first arrival of people.

PMID- 16085712
TI  - The vast majority of bone-marrow-derived cells integrated into mdx muscle fibers
      are silent despite long-term engraftment.
AB  - Bone-marrow-derived cells can contribute nuclei to skeletal muscle fibers.
      However, serial sectioning of muscle in mdx mice implanted with GFP-labeled bone
      marrow reveals that only 20% of the donor nuclei chronically incorporated in
      muscle fibers show dystrophin (or GFP) expression, which is still higher than the
      expected frequency of "revertant" fibers, but there is no overall increase above
      controls over time. Obviously, the vast majority of incorporated nuclei either
      never or only temporarily turn on myogenic genes; also, incorporated nuclei
      eventually loose the activation of the beta-actin::GFP transgene. Consequently,
      we attempted to enhance the expression of dystrophin. In vivo application of the
      chromatin-modifying agents 5-azadeoxycytidine and phenylbutyrate as well as local
      damage by cardiotoxin injections caused a small increase in dystrophin-positive
      fibers without abolishing the appearance of "silent" nuclei. The results thus
      confirm that endogenous repair processes and epigenetic modifications on a small
      scale lead to dystrophin expression from donor nuclei. Both effects, however,
      remain below functionally significant levels.

PMID- 16085713
TI  - Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O
      GlcNAc in diabetes-associated erectile dysfunction.
AB  - Impaired endothelial nitric oxide synthase (eNOS) function is associated with
      erectile dysfunction in diabetes mellitus, but the exact molecular basis for the
      eNOS defect in the diabetic penis remains unclear. We investigated whether
      hyperglycemia increases O-GlcNAc modification of eNOS in the penis, preventing
      phosphorylation at the primary positive regulatory site on the enzyme and
      hampering mechanisms of the erectile response. Type I diabetes mellitus was
      induced in male rats by alloxan (140 mg/kg, i.p.). After 5 wk, the diabetic rat
      penis exhibited increased O-GlcNAc modification of eNOS and decreased eNOS
      phosphorylation at Ser-1177 at baseline compared with the control rat penis; eNOS
      phosphorylation at Thr-495, Ser-615, and Ser-633 was not affected. In addition,
      eNOS phosphorylation at Ser-1177 was impaired in the diabetic rat penis in
      response to penile blood flow (shear stress) elicited by electrical stimulation
      of the cavernous nerve (ES) and to recombinant human VEGF165. Phosphorylation of
      Akt, a mediator of shear stress-induced eNOS phosphorylation at Ser-1177, was
      decreased in the diabetic penis at baseline, but it was restored by ES. Erectile
      response to shear stress elicited by ES and to VEGF was decreased in diabetic
      compared with control rats. This work demonstrates that eNOS inactivation occurs
      in the diabetic penis by a glycosylation mechanism specifically at Ser-1177, by
      which the enzyme is rendered incapable of activation by fluid shear stress
      stimuli and VEGF signaling. In vivo penile erection paradigm supports the
      physiologic relevance of O-GlcNAc modification in vascular disorders associated
      with diabetes.

PMID- 16085716
TI  - Effects of simvastatin within two weeks on anti-inflammatory cytokine interleukin
      10 in patients with unstable angina.

PMID- 16085714
TI  - Caenorhabditis elegans CNK-1 promotes Raf activation but is not essential for
      Ras/Raf signaling.
AB  - Connector enhancer of Ksr (CNK) is a conserved multidomain protein essential for
      Ras signaling in Drosophila melanogaster and thought to be involved in Raf kinase
      activation. However, the precise role of CNK in Ras signaling is not known, and
      mammalian CNKs are proposed to have distinct functions. Caenorhabditis elegans
      has a single CNK homologue, cnk-1. Here, we describe the role of cnk-1 in C.
      elegans Ras signaling and its requirements for LIN-45 Raf activation. We find
      that cnk-1 positively regulates multiple Ras signaling events during development,
      but, unlike Drosophila CNK, cnk-1 does not appear to be essential for signaling.
      cnk-1 mutants appear to be normal but show cell-type-specific genetic
      interactions with mutations in two other Ras pathway scaffolds/adaptors ksr-1 and
      sur-8. Genetic epistasis using various activated LIN-45 Raf transgenes shows that
      CNK-1 promotes LIN-45 Raf activation at a step between the dephosphorylation of
      inhibitory sites in the regulatory domain and activating phosphorylation in the
      kinase domain. Our data are consistent with a model in which CNK promotes Raf
      phosphorylation/activation through membrane localization, oligomerization, or
      association with an activating kinase.

PMID- 16085717
TI  - The CAREGENE study: ACE gene I/D polymorphism and effect of physical training on
      aerobic power in coronary artery disease.

PMID- 16085715
TI  - Cyclin-dependent kinase (CDK) phosphorylation destabilizes somatic Wee1 via
      multiple pathways.
AB  - At the onset of M phase, the activity of somatic Wee1 (Wee1A), the inhibitory
      kinase for cyclin-dependent kinase (CDK), is down-regulated primarily through
      proteasome-dependent degradation after ubiquitination by the E3 ubiquitin ligase
      SCF(beta-TrCP). The F-box protein beta-TrCP (beta-transducin repeat-containing
      protein), the substrate recognition component of the ubiquitin ligase, binds to
      its substrates through a conserved binding motif (phosphodegron) containing two
      phosphoserines, DpSGXXpS. Although Wee1A lacks this motif, phosphorylation of
      serines 53 and 123 (S53 and S123) of Wee1A by polo-like kinase 1 (Plk1) and CDK,
      respectively, are required for binding to beta-TrCP. The sequence surrounding
      phosphorylated S53 (DpSAFQE) is similar to the conserved beta-TrCP-binding motif;
      however, the role of S123 phosphorylation (EEGFGSSpSPVK) in beta-TrCP binding was
      not elucidated. In the present study, we show that phosphorylation of S123
      (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three
      independent mechanisms. The pS123 not only directly interacted with basic
      residues in the WD40 repeat domain of beta-TrCP but also primed phosphorylation
      by two independent protein kinases, Plk1 and CK2 (formerly casein kinase 2), to
      create two phosphodegrons on Wee1A. In the case of Plk1, S123 phosphorylation
      created a polo box domain-binding motif (SpSP) on Wee1A to accelerate
      phosphorylation of S53 by Plk1. CK2 could phosphorylate S121, but only if S123
      was phosphorylated first, thereby generating the second beta-TrCP-binding site
      (EEGFGpS121). Using a specific inhibitor of CK2, we showed that the
      phosphorylation-dependent degradation of Wee1A is important for the proper onset
      of mitosis.

PMID- 16085718
TI  - Coronary microvascular dysfunction in male patients with Anderson-Fabry disease
      and the effect of treatment with alpha galactosidase A.
AB  - OBJECTIVE: To measure coronary flow reserve (CFR), an index of microvascular
      function, in Anderson-Fabry disease (AFD) at baseline and after enzyme
      replacement therapy (ERT). METHODS AND RESULTS: Mean (SD) myocardial blood flow
      (MBF) at rest and during hyperaemia (adenosine 140 microg/kg/min) was measured in
      10 male, non-smoking patients (53.8 (10.9) years, cholesterol 5.5 (1.3) mmol/l)
      and in 24 age matched male, non-smoking controls (52.0 (7.6) years, cholesterol
      4.5 (0.6) mmol/l) by positron emission tomography (PET). Resting and hyperaemic
      MBF and CFR (hyperaemic/resting MBF) were reduced in patients compared with
      controls (0.99 (0.17) v 1.17 (0.25) ml/g/min, p < 0.05; 1.37 (0.32) v 3.44 (0.78)
      ml/g/min, p < 0.0001; and 1.41 (0.39) v 3.03 (0.85), p < 0.0001, respectively).
      This coronary microvascular dysfunction was independent of cholesterol
      concentrations. PET was repeated in five patients after 10.1 (2.3) months of ERT;
      resting and hyperaemic MBF and CFR were unchanged after ERT (0.99 (0.16) v 0.99
      (0.16) ml/g/min; 1.56 (0.29) v 1.71 (0.3) ml/g/min; and 1.6 (0.37) v 1.74 (0.28),
      respectively; all not significant). CONCLUSIONS: The results of the present study
      show that patients with AFD have very abnormal coronary microvascular function.
      These preliminary data suggest that ERT has no effect on coronary microvascular
      dysfunction. Further work is necessary to determine whether treatment at an
      earlier stage in the course of the disease may improve coronary microvascular
      function in patients with AFD.

PMID- 16085719
TI  - Testing requirements for replacing the OTM rule.

PMID- 16085720
TI  - A year of progress: the RCVS annual general meeting.

PMID- 16085721
TI  - Origin and evolution of highly pathogenic H5N1 avian influenza in Asia.
AB  - Outbreaks of highly pathogenic avian influenza caused by H5N1 viruses were
      reported almost simultaneously in eight neighbouring Asian countries between
      December 2003 and January 2004, with a ninth reporting in August 2004, suggesting
      that the viruses had spread recently and rapidly. However, they had been detected
      widely in the region in domestic waterfowl and terrestrial poultry for several
      years before this, and the absence of widespread disease in the region before
      2003, apart from localised outbreaks in the Hong Kong Special Autonomous Region
      (SAR), is perplexing. Possible explanations include limited virus excretion by
      domestic waterfowl infected with H5N1, the confusion of avian influenza with
      other serious endemic diseases, the unsanctioned use of vaccines, and the under
      reporting of disease as a result of limited surveillance. There is some evidence
      that the excretion of the viruses by domestic ducks had increased by early 2004,
      and there is circumstantial evidence that they can be transmitted by wild birds.
      The migratory birds from which viruses have been isolated were usually sick or
      dead, suggesting that they would have had limited potential for carrying the
      viruses over long distances unless subclinical infections were prevalent.
      However, there is strong circumstantial evidence that wild birds can become
      infected from domestic poultry and potentially can exchange viruses when they
      share the same environment. Nevertheless, there is little reason to believe that
      wild birds have played a more significant role in spreading disease than trade
      through live bird markets and movement of domestic waterfowl. Asian H5N1 viruses
      were first detected in domestic geese in southern China in 1996. By 2000, their
      host range had extended to domestic ducks, which played a key role in the genesis
      of the 2003/04 outbreaks. The epidemic was not due to the introduction and spread
      of a single virus but was caused by multiple viruses which were genotypically
      linked to the Goose/GD/96 lineage via the haemagglutinin gene. The H5N1 viruses
      isolated from China, including the Hong Kong SAR, between 1999 and 2004 had a
      range of genotypes and considerable variability within genotypes. The rising
      incidence and widespread reporting of disease in 2003/04 can probably be
      attributed to the increasing spread of the viruses from existing reservoirs of
      infection in domestic waterfowl and live bird markets leading to greater
      environmental contamination. When countries in the region started to report
      disease in December 2003, others were alerted to the risk and disease
      surveillance and reporting improved. The H5N1 viruses have reportedly been
      eliminated from three of the nine countries that reported disease in 2003/04, but
      they could be extremely difficult to eradicate from the remaining countries,
      owing to the existence of populations and, possibly, production and marketing
      sectors, in which apparently normal birds harbour the viruses.

PMID- 16085722
TI  - Persistence of Salmonella Typhimurium DT120 in abattoir paddocks holding sheep.
AB  - In the summer of 1999 there was an outbreak of Salmonella Typhimurium DT120 in
      people in the north of England which was unusual in being sensitive to
      antimicrobial drugs. The outbreak was linked to mutton and lamb from a local
      abattoir, and attention focused on four holding paddocks used to retain sheep
      before slaughter. In November 1999, samples of soil and faeces were taken from
      these paddocks and samples of faeces were taken from the concrete race leading
      from them. Salmonella Typhimurium was isolated from 59 of the 100 samples.
      Between January 2000 and October 2000 seven visits were made to the abattoir at
      each of which 100 samples were taken from the paddocks and concrete race and
      examined for the presence of Salmonella. The paddocks remained heavily
      contaminated with S Typhimurium DT120 until April when there was a marked
      reduction in the recovery of the organism. By June the contamination was minimal
      and by August it had disappeared, and the organism was not recovered in September
      or October.

PMID- 16085724
TI  - Investigation of bovine viral diarrhoea virus-associated abortion in cattle
      vaccinated with inactivated vaccine.

PMID- 16085723
TI  - Japanese encephalitis in a racing thoroughbred gelding in Hong Kong.
AB  - A horse in Hong Kong that had been vaccinated against Japanese encephalitis
      suffered a pyrexic episode that culminated in a hyperexcitable state and self
      inflicted trauma. Japanese encephalitis was diagnosed on the basis of clinical,
      pathological and serological observations, and confirmed by the detection of
      genomic sequences of the virus in spinal cord tissue. Phylogenetic analyses of E
      gene and NS5-3'UTR sequences revealed divergent clustering of these segments with
      previously described genotypes, suggesting the possibility that the horse might
      have been infected with a recombinant between genotype I and genotype II viruses.
      Horses are considered to be dead-end hosts for the disease, but the occurrence of
      an infected horse in a population may have implications for the health status of
      the national herd. The effect that this case had on the horse industry in Hong
      Kong is discussed with specific reference to the movement of horses and the
      vaccination programme for Japanese encephalitis.

PMID- 16085725
TI  - Fungal rhinitis caused by Scedosporium apiospermum in a labrador retriever.

PMID- 16085726
TI  - Investigation of MRSA in small animal practice.

PMID- 16085727
TI  - Symptoms or signs?

PMID- 16085728
TI  - Tapeworm control in sheep.

PMID- 16085729
TI  - Implications of reversibility testing on prevalence and risk factors for chronic
      obstructive pulmonary disease: a community study.
AB  - BACKGROUND: The Global Initiative for Obstructive Lung Disease (GOLD) has defined
      chronic obstructive pulmonary disease (COPD) as a post-bronchodilator ratio of
      forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) of <0.7.
      In the first general population based study to apply post-bronchodilator values,
      the prevalence and predictors of GOLD defined COPD were assessed and the
      implications of beta2 agonist reversibility testing examined. METHODS: Based on a
      random population sample, 2235 subjects (77%) aged 26-82 years performed
      spirometric tests before and 15 minutes after inhaling 0.3 mg salbutamol.
      RESULTS: The prevalence of GOLD defined COPD was 7.0% (95% confidence interval
      (CI) 5.9 to 8.0). This estimate was 27% lower than COPD defined without
      bronchodilatation. One percent of the population had severe or very severe COPD.
      Compared with women, men had 3.1 (95% CI 2.1 to 4.8) times higher odds for COPD.
      Subjects with a smoking history of more than 20 pack years had an odds ratio (OR)
      of 6.2 (95% CI 3.4 to 11.0) for COPD relative to never-smokers, while subjects
      older than 75 years had an OR of 18.0 (95% CI 9.2 to 35.0) relative to those
      below 45 years. Subjects with primary education only had an OR of 2.8 (95% CI 1.4
      to 5.3) compared with those with university education. Subjects with body mass
      index (BMI) <20 kg/m2 were more likely than subjects with BMI 25-29.9 kg/m2 to
      have COPD (OR 2.4, 95% CI 1.1 to 5.3). The adjusted proportion of COPD
      attributable to smoking was 68%. CONCLUSIONS: These results indicate that
      community programmes on prevention of COPD should focus on anti-smoking,
      nutritional aspects, and socioeconomic conditions. The effect of beta2
      reversibility testing on prevalence estimates of COPD was substantial.

PMID- 16085730
TI  - Randomised crossover study of pressure and volume non-invasive ventilation in
      chest wall deformity.
AB  - BACKGROUND: Non-invasive ventilation is an established treatment for chronic
      respiratory failure due to chest wall deformity. There are few data available to
      inform the choice between volume and pressure ventilators. The aim of this study
      was to compare pressure and volume targeted ventilation in terms of diurnal
      arterial blood gas tensions, lung volumes, hypercapnic ventilatory responses,
      sleep quality, and effect on daytime function and health status when ventilators
      were carefully set to provide the same minute ventilation. METHODS: Thirteen
      patients with chest wall deformity underwent a 4 week single blind randomised
      crossover study using the Breas PV403 ventilator in either pressure or volume
      mode with assessments made at the end of each 4 week period. RESULTS: Minute
      ventilation at night was less than that set during the day with greater leakage
      for both modes of ventilation. There was more leakage with pressure than volume
      ventilation (13.8 (1.9) v 5.9 (1.0) l/min, p = 0.01). There were no significant
      differences in sleep quality, daytime arterial blood gas tensions, lung
      mechanics, ventilatory drive, health status or daytime functioning. CONCLUSIONS:
      These data suggest that pressure and volume ventilation are equivalent in terms
      of the effect on nocturnal and daytime physiology, and resulting daytime function
      and health status.

PMID- 16085731
TI  - Splenectomy and chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND: An increased prevalence of splenectomy has been reported in patients
      with idiopathic pulmonary arterial hypertension. Examination of small pulmonary
      arteries from these subjects has revealed multiple thrombotic lesions, suggesting
      that thrombosis may contribute to this condition. Based on these findings, we
      hypothesised that splenectomy could be a risk factor for chronic thromboembolic
      pulmonary hypertension (CTEPH), a condition defined by the absence of thrombus
      resolution after acute pulmonary embolism that causes sustained obstruction of
      the pulmonary arteries and subsequent pulmonary hypertension. METHODS: The
      medical history, clinical characteristics, thrombotic risk factors and
      haemodynamics of 257 patients referred for CTEPH between 1989 and 1999 were
      reviewed. In a case-control study the prevalence of splenectomy in patients with
      CTEPH was compared with that of patients evaluated during the same period for
      idiopathic pulmonary hypertension (n=276) or for lung transplantation in other
      chronic pulmonary conditions (n=180). RESULTS: In patients with CTEPH, 8.6% (95%
      CI 5.2 to 12.0) had a history of splenectomy compared with 2.5% (95% CI 0.7 to
      4.4) and 0.56% (95% CI 0 to 1.6) in cases of idiopathic pulmonary arterial
      hypertension and other chronic pulmonary conditions, respectively (p<0.01).
      CONCLUSION: Splenectomy may be a risk factor for chronic thromboembolic pulmonary
      hypertension.

PMID- 16085732
TI  - A novel treatment for symptomatic carotid dissection.

PMID- 16085733
TI  - Gastric epithelioid haemangioendothelioma: a rare cause of upper gastrointestinal
      bleeding.
AB  - Vascular tumours of the stomach are rare, representing 0.9%-3.3% of all gastric
      neoplasms. A 58 year old man was admitted as an emergency with a one day history
      of haematemesis and melaena. He underwent an emergency laparotomy for a tumour in
      the lesser curve of the stomach. The tumour showed the characteristic
      histological and immunohistochemical features of epithelioid
      haemangioendothelioma. Surgery in the form of wide excision seems to be the
      treatment of choice for this rare neoplasm. This case highlights the difficulty
      in diagnosing this rare tumour preoperatively and emphasises the need for long
      term follow up in view of its uncertain metastatic potential.

PMID- 16085734
TI  - A 30 month old child with changed sensorium.

PMID- 16085735
TI  - Swelling of volar aspect of the wrist.

PMID- 16085736
TI  - Does innate immune response defect underlie inflammatory bowel disease in the
      Asian population?

PMID- 16085737
TI  - Diabetes and ethnic minorities.
AB  - The global prevalence of diabetes for all age groups is estimated to be 2.8%.
      Type 2 diabetes accounts for at least 90% of diabetes worldwide. Diabetes
      incidence, prevalence, and disease progression varies by ethnic group. This
      review highlights unique aspects of the risk of developing diabetes, its
      overwhelming vascular complications, and their management mainly using data among
      South Asians and African-Caribbeans in the UK but also using non-UK data. It is
      concluded that although the origin of the ethnic differences in incidence need
      further clarification, many factors should be amenable to prevention and
      treatment in all ethnic groups worldwide.

PMID- 16085738
TI  - Diagnosis and management of chronic pancreatitis.
AB  - Chronic pancreatitis represents a condition that is challenging for clinicians
      secondary to the difficulty in making an accurate diagnosis and the less than
      satisfactory means of managing chronic pain. This review emphasises the various
      manifestations that patients with chronic pancreatitis may have and describes
      recent advances in medical and surgical therapy. It is probable that many
      patients with chronic abdominal pain are suffering from chronic pancreatitis that
      is not appreciated. As the pathophysiology of this disorder is better understood
      it is probable that the treatment will be more successful.

PMID- 16085739
TI  - Dermatology spot diagnosis.

PMID- 16085740
TI  - The approach to patients with "non-epileptic seizures".
AB  - Up to one fifth of patients who present to specialist clinics with seizures do
      not have epilepsy. The majority of such patients suffer from psychologically
      mediated episodes; dissociative seizures, often referred to as "non-epileptic
      seizures". This paper describes the diagnostic evaluation of seizure disorders,
      including clinical assessment and the role of special investigations. The organic
      and psychiatric imitators of epilepsy are outlined and findings on psychiatric
      assessment are reviewed. This group of patients often proves difficult to engage
      in appropriate treatment and an approach to explaining the diagnosis is
      described. As yet there are no controlled trials of treatment in this disorder
      but preliminary evidence suggests cognitive behavioural therapy is both a
      rational and promising way forward.

PMID- 16085741
TI  - Malaria in the post-genomics era: light at the end of the tunnel or just another
      train?
AB  - Malaria remains the third leading cause of death attributable to an infectious
      disease worldwide, with an estimated death toll of over 2 million per year,
      predominately in sub-Saharan Africa. The first serious attempt to eradicate this
      disease was unsuccessful, and 50 years later in 1998 a second programme coined
      "roll back malaria" was started. While this programme is at present unlikely to
      reach its stated aims, the completion of the genome sequencing projects on the
      human host, the mosquito vector, and the malaria parasite offers new hope. It is
      probable that the burden of disease caused by the most malignant form of the
      parasite Plasmodium falciparum can be, if not eliminated, then effectively
      suppressed within a generation through new and novel treatments aimed at all
      three arms of malaria control.

PMID- 16085742
TI  - Mechanisms underlying recovery of motor function after stroke.
AB  - Neurological damage, and stroke in particular, is the leading cause of long term
      disability worldwide. There is growing interest in the part that central nervous
      system reorganisation plays in recovery of function. Techniques such as
      functional magnetic resonance imaging and transcranial magnetic stimulation
      permit the non-invasive study of the working human brain, and suggest that
      functionally relevant adaptive changes occur in the human brain after focal
      damage. An understanding of how these changes are related to recovery will
      facilitate the development of novel therapeutic techniques that are based on
      neurobiological principles and that are designed to minimise impairment in
      appropriately targeted patients suffering from stroke.

PMID- 16085743
TI  - The heart and the oesophagus: intimate relations.
AB  - The close anatomical relations of the heart and oesophagus, and the similarity of
      symptoms attributable to disorders of either organ, often lead to diagnostic
      difficulty in patients with chest pain. A definitive diagnosis of non-cardiac
      chest pain attributable to oesophageal reflux or spasm is hampered, both by the
      need for prolonged ambulatory monitoring of pH, manometry, and endoscopy, and by
      the common occurrence of asymptomatic reflux and spasm, and the corresponding
      difficulty in linking an episode of reflux or spasm with an episode of pain.
      Moreover, some patients with non-cardiac chest pain and normal tests of
      oesophageal structure and function have centrally mediated hypersensitivity, both
      within and without the oesophagus. Rather than proceed with investigations, in
      the absence of symptoms to suggest structural disease of the oesophagus, it would
      be reasonable to attempt symptomatic treatment with a proton pump inhibitor or an
      antidepressant.

PMID- 16085744
TI  - Meeting the non-clinical education and training needs of new consultants.
AB  - This review highlights the non-clinical training needs of new consultants,
      identifying strategies for meeting these needs. Non-clinical activities are
      integral to the consultant's role and senior clinicians need training in these
      areas. Concerns over the quantity and quality of current provision are compounded
      by changes the European Working Time Directive and Modernising Medical Careers
      initiative will bring. Accelerated progression to senior level and reduction in
      time for training suggest a pressing need to respond to the needs of new
      consultants. Ad hoc initiatives in a range of healthcare contexts offer examples
      of how training needs may be met, including mentoring and continuing professional
      development schemes. A multi-professional strategy, incorporating elements of
      higher professional education in general practice and other NHS initiatives
      (particularly management/leadership training), may offer an appropriate framework
      within which to capitalise on existing opportunities. There are, however,
      resource implications that need to be addressed.

PMID- 16085745
TI  - Do weekend plan standard forms improve communication and influence quality of
      patient care?
AB  - Weekends are critical times in an inpatient stay, when daily review of patients
      is not routine and the usual team of doctors responsible for a patient's care is
      often not available. Communication between the patient's own doctors and the on
      call team is vital for continuity of care and to maintain patient safety. The
      provision and completeness of weekend plans was assessed before and after the
      introduction of a standard form. The introduction of the form led to a
      significant improvement in the proportion of notes containing a weekend plan and
      the proportion of notes containing a resuscitation decision (p<0.05), which will
      have a significant impact on patient care.

PMID- 16085746
TI  - Polymorphisms of CD14 gene and TLR4 gene are not associated with ulcerative
      colitis in Chinese patients.
AB  - BACKGROUND AND AIMS: Toll-like receptor 4 and CD14 are the components of the
      lipopolysaccharide receptor complex. The aim of this study was to investigate the
      associations between polymorphisms TLR4 Asp299Gly and CD14 C-260T and Chinese
      patients with ulcerative colitis (UC). METHODS: Using a polymerase chain reaction
      based restriction fragment length polymorphism, the study genotyped polymorphisms
      TLR4 Asp299Gly and CD14 C-260T in 114 patients with UC and 160 healthy controls
      in the Chinese Han population. Moreover a comparison was made with 170 healthy
      Dutch white subjects. RESULTS: No TLR4 Asp299Gly mutation was detected in any
      patients or healthy controls in the Chinese Han population, which was similar to
      Japanese subjects, but the mutation occurred in 10% of the Dutch white subjects.
      There were no significant differences of CD14 genotypes between healthy controls
      and the patients with UC.

PMID- 16085747
TI  - Clinical features and follow up of 302 patients with Mycobacterium kansasii
      pulmonary infection: a 50 year experience.
AB  - AIMS: To analyse clinical features and treatment outcomes of patients with
      pulmonary Mycobacterium kansasii infection treated at Hines VA Hospital between
      1952 and 1995, and followed up until 2003. FINDINGS: 302 patients were confirmed
      to have M kansasii pulmonary infection; diagnosis was not made until death in 2%.
      The average age was 50 years old; 76% were white; all were men. Productive cough,
      dyspnoea, and chest pain were common; 16% were asymptomatic. Right sided, apical
      or subapical, thin walled cavitary infiltrate was the characteristic radiological
      feature. Heavy smoking, chronic obstructive pulmonary disease, alcoholism, peptic
      ulcer disease, coronary artery disease, prior tuberculosis, psychosis, prior
      pneumonia, and immunocompromising conditions were prevalent. Average follow up
      was 10 years and 2 months. PPD was positive in 58% of 179 tested. Two thirds of
      the patients required only first line drugs. Fourteen per cent required surgical
      intervention, none after 1977. Spontaneous resolution occurred in 1%.
      Aspergillosis developed in 4%. Bronchogenic carcinoma coexisted with M kansasii
      infection in 6% and followed it in 4%. Extrapulmonary malignancy coexisted with
      the infection in 4% and followed it in 6%; most involved head and neck. Eleven
      per cent of 224 deaths were attributed to M kansasii. Outcomes were affected by
      comorbidity, treatment compliance, rifampicin use, and extent of infection.
      CONCLUSIONS: Prognosis of M kansasii pulmonary infection is good if diagnosed and
      treated early, together with control of underlying conditions. Clinicians should
      be aware of atypical radiological manifestations of the disease when coexisting
      with other pulmonary or immunocompromising conditions.

PMID- 16085748
TI  - Well leg compartment syndrome after pelvic and perineal surgery in the lithotomy
      position.
AB  - OBJECTIVE: Lower limb compartment syndrome after prolonged surgical procedures
      performed in the lithotomy position is a rare but potentially devastating
      complication. It is recognised after urological, colorectal, and gynaecological
      procedures. Sixteen cases of compartment syndrome after urological surgery have
      been reported. The objective of this study was to estimate the incidence of this
      complication in urological practice and identify risk factors for its
      development. DESIGN: A postal survey of UK consultant urologists was conducted.
      RESULTS: Replies were received from 261 consultants. In total there were 65 cases
      of compartment syndrome. Compartment syndrome occurred after radical cystectomy
      and urinary diversion in 51 cases and was rare in procedures lasting less than
      four hours. The incidence of compartment syndrome after cystectomy was estimated
      at around 1 in 500 cases. Risk factors for its development included perioperative
      blood loss, peripheral vascular disease, and obesity. CONCLUSIONS: Compartment
      syndrome after use of the lithotomy position may be more common than is generally
      appreciated and has been underreported in the past. All staff should be aware of
      this serious complication and adopt strategies for its avoidance.

PMID- 16085749
TI  - Laparoscopic colorectal surgery: learning curve and training implications.
AB  - AIMS: This paper is a review of experience of laparoscopic colorectal surgery at
      a district general hospital with particular emphasis on the learning curve and
      training implications. METHODS: All patients undergoing colorectal surgery where
      laparoscopy was attempted between March 1998 and October 2003 were included in
      this study. RESULTS: There were 80 patients of which 49 had malignancy. Twenty
      eight stomas and 52 bowel resections were performed laparoscopically. The
      conversion rate for bowel resection was 32% (decreasing from 38% to 44% to 22%).
      This was significant (p = 0.001) when compared with stoma formation (7%). The
      firm has support from a specialist registrar and staff grade surgeon. In 22% of
      cases, one of the middle grades was the principal operating surgeon, mainly
      laparoscopic mobilisation and stoma formation. Only 6% of resections were
      performed by the middle grades. Conversely, a middle grade was the main operating
      surgeon in 66% of open resections and 61% of stoma formations during the same
      period. There were in all two deaths and 14 postoperative complications. All
      patients who had laparoscopic resections for malignancy had clear resection
      margins. CONCLUSION: This audit highlights that there is a long learning curve in
      laparoscopic colorectal surgery with decrease in conversion rates with increasing
      experience. There is also a reduction in training opportunities in open surgery
      during the learning phase of the consultant, although this may be counterbalanced
      by the exposure to laparoscopic techniques. Laparoscopic colonic mobilisation, as
      a part of stoma formation, is a good starting point for specialist registrar
      training.

PMID- 16085750
TI  - Acanthosis nigricans: relation with type 2 diabetes mellitus, anthropometric
      variables, and body mass in Indians.
AB  - OBJECTIVE: To determine the prevalence of acanthosis nigricans (AN) in type 2
      diabetes mellitus (T2DM) and its correlation with various anthropometric
      measurements in Indians. METHODS: One hundred and fifty consecutive subjects with
      T2DM attending the diabetes clinic at a tertiary referral centre in North India
      were considered as cases and 150 age and sex matched healthy attendants of non
      diabetic subjects as controls. All the cases and controls were screened for the
      presence of AN and its severity. Anthropometric measurements of all of them were
      measured in standard method. Regression analysis was done to determine the
      association of AN with T2DM and various anthropometric measurements. RESULTS: The
      prevalence of AN in subjects with diabetes and healthy controls was 62.6% and 40%
      respectively, and this difference was significant (p<0.05). Body mass index (BMI)
      between cases and controls was comparable by chance. There was a statistically
      significant correlation of increasing severity of AN with increasing BMI, waist
      circumference, hip circumference, waist-hip ratio, skinfold thickness, and body
      fat percentage in diabetic patients. However, in regression analysis after
      considering all the confounding factors there was a significant correlation of
      AN, only with diabetes mellitus and BMI. CONCLUSIONS: Indians have high
      prevalence of AN and it is an independent cutaneous marker of both T2DM and BMI.

PMID- 16085751
TI  - Electrochemically directed synthesis of oligonucleotides for DNA microarray
      fabrication.
AB  - We demonstrate a new method for making oligonucleotide microarrays by synthesis
      in situ. The method uses conventional DNA synthesis chemistry with an
      electrochemical deblocking step. Acid is delivered to specific regions on a glass
      slide, thus allowing nucleotide addition only at chosen sites. The acid is
      produced by electrochemical oxidation controlled by an array of independent
      microelectrodes. Deblocking is complete in a few seconds, when competing side
      product reactions are minimal. We demonstrate the successful synthesis of 17mers
      and discrimination of single base pair mismatched hybrids. Features generated in
      this study are 40 mum wide, with sharply defined edges. The synthetic technique
      may be applicable to fabrication of other molecular arrays.

PMID- 16085752
TI  - Initiation of DNA replication at the human beta-globin 3' enhancer.
AB  - The origin of DNA replication in the human beta-globin gene contains an
      initiation region (IR) and two flanking auxiliary elements. Two replicator
      modules are located within the upstream auxiliary sequence and the IR core, but
      the functional sequences in the downstream auxiliary element are unknown. Here,
      we use a combination of benzoylated-naphthoylated DEAE (BND) cellulose
      purification and nascent strand abundance assays to show that replication
      initiation occurs at the beta-globin 3' enhancer on human chromosome 11 in the
      Hu11 hybrid murine erythroleukemia (MEL) cell line. To examine replicator
      function, 3' enhancer fragments were inserted into an ectopic site in MEL cells
      via an optimized FRT/EGFP-FLP integration system. These experiments demonstrate
      that the 1.6 kb downstream auxiliary element is a third replicator module called
      bGRep-E in erythroid cells. The minimal 260 bp 3' enhancer is required but not
      sufficient to initiate efficient replication, suggesting cooperation with
      adjacent sequences. The minimal 3' enhancer also cooperates with elements in an
      expressing HS3beta/gamma-globin construct to initiate replication. These data
      indicate that the beta-globin replicator has multiple initiation sites in three
      closely spaced replicator modules. We conclude that a mammalian enhancer can
      cooperate with adjacent sequences to create an efficient replicator module.

PMID- 16085753
TI  - Curved DNA molecules migrate anomalously slowly in free solution.
AB  - The electrophoretic mobility of a curved DNA restriction fragment taken from the
      VP1 gene in the SV40 minichromosome has been measured in polyacrylamide gels and
      free solution, using capillary electrophoresis. The 199 bp restriction fragment
      has an apparent bend angle of 46 +/- 2 degrees located at SV40 sequence position
      1922 +/- 2 bp [Lu Y.J., Weers B.D. and Stellwagen N. C. (2005) Biophys. J., 88,
      1191-1206]. The 'curvature module' surrounding the apparent bend center contains
      five unevenly spaced A- and T-tracts, which are responsible for the observed
      curvature. The parent 199 bp fragment and sequence mutants containing at least
      one A-tract in the curvature module migrate anomalously slowly in free solution,
      as well as in polyacrylamide gels. Hence, the anomalously slow mobilities
      observed for curved DNA molecules in polyacrylamide gels are due in part to their
      anomalously slow mobilities in free solution. Analysis of the gel and free
      solution mobility decrements indicates that each A- or T-tract contributes
      independently, but not equally, to the curvature of the 199 bp fragment and its A
      tract mutants. The relative contribution of each A- or T-tract to the observed
      curvature depends on its spacing with respect to the first A-tract in the
      curvature module.

PMID- 16085754
TI  - The Rhodomonas salina mitochondrial genome: bacteria-like operons, compact gene
      arrangement and complex repeat region.
AB  - To gain insight into the mitochondrial genome structure and gene content of a
      putatively ancestral group of eukaryotes, the cryptophytes, we sequenced the
      complete mitochondrial DNA of Rhodomonas salina. The 48 063 bp circular-mapping
      molecule codes for 2 rRNAs, 27 tRNAs and 40 proteins including 23 components of
      oxidative phosphorylation, 15 ribosomal proteins and two subunits of tat
      translocase. One potential protein (ORF161) is without assigned function. Only
      two introns occur in the genome; both are present within cox1 belong to group II
      and contain RT open reading frames. Primitive genome features include bacteria
      like rRNAs and tRNAs, ribosomal protein genes organized in large clusters
      resembling bacterial operons and the presence of the otherwise rare genes such as
      rps1 and tatA. The highly compact gene organization contrasts with the presence
      of a 4.7 kb long, repeat-containing intergenic region. Repeat motifs
      approximately 40-700 bp long occur up to 31 times, forming a complex repeat
      structure. Tandem repeats are the major arrangement but the region also includes
      a large, approximately 3 kb, inverted repeat and several potentially stable
      approximately 40-80 bp long hairpin structures. We provide evidence that the
      large repeat region is involved in replication and transcription initiation,
      predict a promoter motif that occurs in three locations and discuss two likely
      scenarios of how this highly structured repeat region might have evolved.

PMID- 16085755
TI  - Predicting specificity-determining residues in two large eukaryotic transcription
      factor families.
AB  - Certain amino acid residues in a protein, when mutated, change the protein's
      function. We present an improved method of finding these specificity-determining
      positions that uses all the protein sequence data available for a family of
      homologous proteins. We study in detail two families of eukaryotic transcription
      factors, basic leucine zippers and nuclear receptors, because of the large amount
      of sequences and experimental data available. These protein families also have a
      clear definition of functional specificity: DNA-binding specificity. We compare
      our results to three other methods, including the evolutionary trace algorithm
      and a method that depends on orthology relationships. All of the predictions are
      compared to the available mutational and crystallographic data. We find that our
      method provides superior predictions of the known specificity-determining
      residues and also predicts residue positions within these families that deserve
      further study for their roles in functional specificity.

PMID- 16085757
TI  - Short-term exposure of renal proximal tubules to gentamicin increases long-term
      multidrug resistance protein 2 (Abcc2) transport function and reduces
      nephrotoxicant sensitivity.
AB  - We previously showed that the function of renal multidrug resistance protein
      (Mrp) 2 (Abcc2) is reduced by endothelin (ET)-1 signaling through an ET(B)
      receptor, nitric-oxide synthase (NOS), cGMP, and protein kinase C and that this
      pathway was activated by several nephrotoxicants (Masereeuw et al., 2000; Terlouw
      et al., 2001; Notenboom et al., 2002, 2004). Here, we determined the long-term
      effects on Mrp2-mediated transport (luminal fluorescein methotrexate
      accumulation) of short-term (30 min) exposure to ET-1 and the aminoglycoside
      antibiotic, gentamicin. Our data show that over the 3 h following exposure,
      proximal tubules recovered fully from the initial decrease in Mrp2-mediated
      transport and that transport activity was not changed 9 h later. However, 24 h
      after exposure, luminal accumulation of an Mrp2 substrate had increased by 50%.
      Increased transport at 24 h was accompanied by an increased transporter protein
      content of the luminal plasma membrane as measured by immunostaining. Blocking ET
      1 signaling at the ET(B) receptor or downstream at NOS or guanylyl cyclase
      abolished both stimulation of transport and increased transporter expression.
      Thus, regardless of whether signaling was initiated by a short exposure to ET-1
      or to a nephrotoxicant, the time course of Mrp2 response to ET(B) signaling was
      the same and was multiphasic. Finally, when tubules were exposed to gentamicin
      for 30 min and removed to gentamicin-free medium for 24 h, they were less
      sensitive to acute gentamicin toxicity than paired controls not initially exposed
      to the drug. Thus, short-term exposure to ET-1 or gentamicin resulted in long
      term protection against a second insult.

PMID- 16085756
TI  - Kinetic resolution of bimolecular hybridization versus intramolecular folding in
      nucleic acids by surface plasmon resonance: application to G-quadruplex/duplex
      competition in human c-myc promoter.
AB  - The human oncogene c-myc is regulated by G-quadruplex formation within the
      nuclease hypersensitive element (NHE III(I)) in the c-myc promoter, making the
      quadruplex a strong anti-cancer target. With respect to this, the competing
      equilibrium between intramolecular quadruplex folding and bimolecular duplex
      formation is poorly understood and very few techniques have addressed this
      problem. We present a method for simultaneously determining the kinetic constants
      for G-quadruplex folding/unfolding and hybridization in the presence of the
      complementary strand from a single reaction using an optical biosensor based on
      surface plasmon resonance (SPR). Using this technique, we demonstrate for the
      first time that quadruplex formation in the c-myc promoter is favored at low
      strand concentrations. Our results indicate favorable quadruplex folding
      (equilibrium folding constant K(F) of 2.09 calculated from the kinetic
      parameters: folding rate constant, k(f) = 1.65 x 10(-2) s(-1) and unfolding rate
      constant, k(u) = 7.90 x 10(-3) s(-1)) in 150 mM K+. The hybridization rate
      constants detected concurrently gave a bimolecular association constant, k(a) =
      1.37 x 10(5) M(-1) s(-1) and dissociation constant, k(d) = 4.94 x 10(-5) s(-1).
      Interestingly, in the presence of Na+ we observed that G-quadruplex folding was
      unfavorable (K(F) = 0.54). Implication of our results on the c-myc transcription
      activation model is discussed in light of aberrant c-myc expression observed on
      destabilization of the G-quadruplex.

PMID- 16085758
TI  - Pharmacoproteomic effects of isoniazid, ethambutol, and N-geranyl-N'-(2
      adamantyl)ethane-1,2-diamine (SQ109) on Mycobacterium tuberculosis H37Rv.
AB  - The present study was aimed at fingerprinting pharmacoproteomic alterations of
      the Mycobacterium tuberculosis H37Rv strain induced by antitubercular drugs
      isoniazid (INH), ethambutol (EMB), and SQ109 [N-geranyl-N'-(2-adamantyl)ethane
      1,2-diamine, a novel 1,2-diamine-based EMB analog], providing new understanding
      of pharmacoproteomic mechanisms of each and exploring new drug targets. The three
      drugs produced significant down-regulation of 13 proteins, including immunogenic
      ModD, Mpt64, with proteins from the Pro-Glu family being inhibited the most.
      Alternatively, the three drugs up-regulated 17 proteins, including secreted
      antigenic proteins ESAT-6 and CFP-10. Among these, ESAT-6 and AphC were most
      affected by INH, whereas EMB had the greatest effect on ESAT-6. All three drugs
      produced only moderate up-regulation of aerobic and iron metabolism proteins,
      i.e., electron transfer flavoprotein Fix A and Fix B, and ferritin-like protein
      BfrB, suggesting that the interruption of microbacterial energy metabolism is not
      a primary mechanism of action. INH suppressed ATP-dependent DNA/RNA helicase, but
      up-regulated beta-ketoacyl-acyl carrier protein synthase. These effects may
      contribute to its bactericidal effects. In contrast, EMB and SQ109 did just the
      opposite: these drugs up-regulated the helicase and down-regulated the synthase.
      For most of the H37Rv proteins, similar pharmacoproteomic patterns were found for
      both EMB and SQ109. None of the drugs significantly regulated expression of
      chaperonins GroES, GroEL2, and Dnak, suggesting that these drugs do not affect
      chaperone-mediated nascent polypeptide folding and sorting. The present study
      identified proteins directly modulated by the actions of INH, EMB, and SQ109 and
      distinguished INH activity from the diamine antitubercular compounds that inhibit
      M. tuberculosis H37Rv.

PMID- 16085759
TI  - Despite similar anxiolytic potential, the 5-hydroxytryptamine 2C receptor
      antagonist SB-242084 [6-chloro-5-methyl-1-[2-(2-methylpyrid-3-yloxy)-pyrid-5-yl
      carbamoyl] indoline] and chlordiazepoxide produced differential effects on
      electroencephalogram power spectra.
AB  - Serious efforts have been made to develop anxiolytics with improved clinical
      utility and reduced side effects. 5-Hydroxytryptamine (5-HT)(2C) receptor
      antagonists are potential anxiolytics; however, their effects on vigilance are
      not well characterized. To compare the effects of benzodiazepines and subtype
      selective 5-HT(2C) receptor antagonists on anxiety, vigilance, and
      electroencephalogram (EEG) power density, social interaction test and polygraphic
      recordings were performed in male Sprague-Dawley rats after chlordiazepoxide
      (CDP; 4.0 mg/kg i.p.) and SB-242084 (6-chloro-5-methyl-1-[2-(2-methylpyrid-3
      yloxy)-pyrid-5-yl carbamoyl] indoline) (0.1, 0.3, and 1.0 mg/kg i.p.) treatment.
      CDP and SB-242084 (0.3 and 1.0 mg/kg) had similar anxiolytic effects. Spectral
      analysis of EEG in wakefulness (W) and paradoxical sleep (PS) showed an opposite
      effect on activity (5-9 Hz); it decreased after CDP, whereas it increased after
      SB-242084 (even at 0.1 mg/kg). In addition, CDP significantly decreased slow-wave
      activity (0.5-4 Hz) in deep slow-wave sleep (SWS-2) and increased power at
      frequencies above 12 Hz mainly in W and PS. A markedly increased intermediate
      stage of sleep was also found after CDP treatment. At the highest dose, SB-242084
      increased W and decreased SWS-2. In summary, low but potent anxiolytic doses of
      the subtype-selective 5-HT(2C) receptor antagonist SB-242084 did not affect
      vigilance states but caused an increased activity in W, raising the possibility
      of a cognitive-enhancing effect of the drug. In contrast, acute CDP
      administration, based on spectral analysis of the EEG, produced a more
      superficial sleep along with a decreased activity.

PMID- 16085760
TI  - Estrous cycle alters naphthalene metabolism in female mouse airways.
AB  - Previous studies have shown variability in naphthalene cytotoxicity, expression
      of CYP2F2 gene and protein, and naphthalene metabolism in random cycling female
      mice (NIH:Swiss). CYP2F2 metabolizes naphthalene to cytotoxic metabolites in
      lungs of mice. This study was designed to address the question: do hormonal
      changes associated with the estrous cycle alter metabolism of naphthalene in the
      lung? Adult virgin female mice were manipulated into defined stages of the
      reproductive cycle: estrus, proestrus, and noncycling. Cycling was confirmed by
      cytology on vaginal swabs. At specific cycle times, extrapulmonary (tracheal and
      bronchial) and intrapulmonary (bronchiolar) conducting airways were
      microdissected from the lung parenchyma and incubated with naphthalene, and the
      products of naphthalene metabolism were trapped and measured using high
      performance liquid chromatography. Circulating estradiol levels were measured at
      necropsy using an enzyme-linked immunosorbent assay. CYP2F2 gene expression was
      determined by airway level using real-time reverse transcription-polymerase chain
      reaction and did not vary by estrous cycle stage in intrapulmonary airways but
      did in extrapulmonary airways. Metabolism of naphthalene varied significantly by
      estrous cycle stage with the highest level of total metabolism occurring in
      proestrus (when estrogen is lowest) in intrapulmonary airways. Total activity and
      metabolite profiles in both extrapulmonary and intrapulmonary airways were
      affected by cycle stage. We conclude that the hormonal patterns associated with
      different stages of the estrous cycle 1) alter metabolism of naphthalene in the
      lungs of mice and 2) alter naphthalene metabolism differentially in
      extrapulmonary versus intrapulmonary airways.

PMID- 16085761
TI  - Diffusion of cholesterol and its precursors in lipid membranes studied by 1H
      pulsed field gradient magic angle spinning NMR.
AB  - Cholesterol content is critical for membrane functional properties. We studied
      the influence of cholesterol and its precursors desmosterol and lanosterol on
      lateral diffusion of phospholipids and sterols by1H pulsed field gradients (PFG)
      magic angle spinning (MAS) NMR spectroscopy. The high resolution of resonances
      afforded by MAS NMR permitted simultaneous diffusion measurements on 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and sterols. The cholesterol
      diffusion mirrored the DPPC behavior, but rates were slightly higher at all
      cholesterol concentrations. DPPC and cholesterol diffusion rates decreased and
      became cholesterol concentration dependent with the onset of liquid-ordered phase
      formation. The activation energies of diffusion in the coexistence region of
      liquid-ordered/liquid-disordered phases are higher by about a factor of 2
      compared to pure DPPC and to the pure liquid-ordered state formed at higher
      cholesterol concentrations. We assume that the higher activation energies are a
      reflection of lipid diffusion across domain boundaries. In lanosterol- and
      desmosterol-containing membranes, the DPPC and sterol diffusion coefficients are
      somewhat higher. Whereas the desmosterol rates are only slightly higher than
      those of DPPC, the lanosterol diffusion rates significantly exceed DPPC rates,
      indicating a weaker interaction between DPPC and lanosterol.

PMID- 16085762
TI  - Unfolding and extraction of a transmembrane alpha-helical peptide: dynamic force
      spectroscopy and molecular dynamics simulations.
AB  - An atomic force microscope (AFM) was used to visualize CWALP(19)23 peptides
      ((+)H(3)N-ACAGAWWLALALALALALALWWA-COO(-)) inserted in gel-phase DPPC and DSPC
      bilayers. The peptides assemble in stable linear structures and domains. A model
      for the organization of the peptides is given from AFM images and a 20 ns
      molecular dynamics (MD) simulation. Gold-coated AFM cantilevers were used to
      extract single peptides from the bilayer through covalent bonding to the cystein
      residue. Experimental and simulated force curves show two distinct force maxima.
      In the simulations these two maxima correspond to the extraction of the two pairs
      of tryptophan residues from the membrane. Unfolding of the peptide precedes
      extraction of the second distal set of tryptophans. To probe the energies
      involved, AFM force curves were obtained from 10 to 10(4) nm/s and MD force
      curves were simulated with 10(8)-10(11) nm/s pulling velocities (V). The velocity
      relationship with the force, F, was fitted to two fluctuation adhesive potential
      models. The first assumes the pulling produces a constant bias in the potential
      and predicts an F approximately ln (V) relationship. The second takes into
      account the ramped bias that the linker feels as it is being driven out of the
      adhesion complex and scales as F approximately (ln V)2/3.

PMID- 16085763
TI  - Structure of bacterial extracellular polymeric substances at different pH values
      as determined by SAXS.
AB  - Extracellular polymeric substances (EPS) play an important role in cell
      aggregation, cell adhesion, and biofilm formation, and protect cells from a
      hostile environment. The EPS was isolated by trichloroacetic acid/ethanol
      extraction from broth culture of a marine bacterium isolate. The EPS was composed
      of glucose and galactose as determined by HPLC and TLC; the protein content was
      on average 15 +/- 5% of EPS dry mass. The solution structure of EPS at different
      values of pH was revealed by small-angle x-ray scattering. Scattering curves of
      EPS solutions (0.4%, w/v) consistently showed two nearly linear log-log regions
      with slopes a and b in the q-ranges from 0.06 nm(-1) to 0.26 nm(-1), and from
      0.27 nm(-1) to 0.88 nm(-1), respectively. Slope a was sensitive to pH changes
      whereas slope b was not. The observed sensitivity to pH was not a consequence of
      ionic strength variation with pH, as checked by salt addition. The pH variation
      causes major rearrangements of EPS structure mainly at length scales above 24 nm.
      To get a better understanding of the pH effect on EPS structure, the original
      model proposed by Geissler was refined into a mathematical model that enabled
      fitting of the experimental scattering curves in the pH range from 0.7 to 11.0.
      The model describes EPS structure as a network of randomly coiled polymeric
      chains with denser domains of polymeric chains. The results obtained from the
      model indicate that dense domains increase in average size from 19 nm at pH 11.0
      to 52 nm at pH 0.7. The average distance between the polysaccharide chains at pH
      0.7 was 2.3 nm, which indicates a compact EPS structure. Swelling was found to be
      at a maximum around pH = 8.8, where the average distance between the chains was
      4.8 nm.

PMID- 16085764
TI  - Distinguishing modes of eukaryotic gradient sensing.
AB  - We develop a mathematical model of phosphoinositide-mediated gradient sensing
      that can be applied to chemotactic behavior in highly motile eukaryotic cells
      such as Dictyostelium and neutrophils. We generate four variants of our model by
      adjusting parameters that control the strengths of coupled positive feedbacks and
      the importance of molecules that translocate from the cytosol to the membrane.
      Each variant exhibits a qualitatively different mode of gradient sensing.
      Simulations of characteristic behaviors suggest that differences between the
      variants are most evident at transitions between efficient gradient detection and
      failure. Based on these results, we propose criteria to distinguish between
      possible modes of gradient sensing in real cells, where many biochemical
      parameters may be unknown. We also identify constraints on parameters required
      for efficient gradient detection. Finally, our analysis suggests how a cell might
      transition between responsiveness and nonresponsiveness, and between different
      modes of gradient sensing, by adjusting its biochemical parameters.

PMID- 16085765
TI  - Ligand-induced DNA condensation: choosing the model.
AB  - We test and compare different models for ligand-induced DNA condensation. Using
      14C-labeled spermidine3+, we measure the binding to condensed DNA at micromolar
      to molar polyamine concentrations. DNA aggregates at a critical polyamine
      concentration. Spermidine3+ binding becomes highly cooperative at the onset of
      aggregation. At higher concentrations, spermidine3+ binding to condensed DNA
      reaches a plateau with the degree of binding equal to 0.7 (NH(4+)/PO3-).
      Condensed DNA exists in a wide range of spermidine concentrations with the
      roughly constant degree of ligand binding. At greater concentrations, the degree
      of binding increases again. Further spermidine penetration between the double
      helices causes DNA resolubilization. We show that a simple two-state model
      without ligand-ligand interactions qualitatively predicts the reentrant
      aggregation-resolubilization behavior and the dependence on the ligand, Na+, and
      DNA concentrations. However, such models are inconsistent with the cooperative
      ligand binding to condensed DNA. Including the contact or long-range ligand
      ligand interactions improves the coincidence with the experiments, if binding to
      condensed DNA is slightly more cooperative than to the starting DNA. For example,
      in the contact interaction model it is equivalent to an additional McGhee-von
      Hippel cooperativity parameter of approximately 2. Possible physical mechanisms
      for the observed cooperativity of ligand binding are discussed.

PMID- 16085766
TI  - Optimizing oriented planar-supported lipid samples for solid-state protein NMR.
AB  - Sample orientation relative to the static magnetic field of an NMR spectrometer
      allows study of membrane proteins in the lipid bilayer setting. The
      straightforward preparation and handling of extremely thin mica substrates with
      consistent surface properties has prompted us to examine oriented phospholipid
      bilayer and hexagonal phases on mica. The spectral characteristics of oriented
      lipid samples formed on mica are as good as or better than those on glass. Nine
      solvents with varying dielectric constants were used to cast lipid films or for
      vesicle spreading; film characteristics were then compared, and static solid
      state 31P-NMR was used to characterize the degree of orientation of the hydrated
      lipid species. Lipids with four headgroup chemistries were tested: 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphoglycerol (POPG), 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA), and 1,2
      dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Solvent affected orientation of
      POPG, DOPA, and DOPE, but not POPC. Film characteristics varied with solvent,
      with ramifications for producing homogeneous oriented lipid samples. POPC was
      used to optimize the amount of lipid per substrate and compare hydration methods.
      POPG did not orient reproducibly, whereas POPG-POPC mixtures did. DOPA showed 1-2
      oriented states depending upon hydration level and deposition method. DOPE formed
      an oriented hexagonal phase that underwent a reversible temperature-induced phase
      transition to the oriented bilayer phase.

PMID- 16085767
TI  - Conductance and ion selectivity of a mesoscopic protein nanopore probed with
      cysteine scanning mutagenesis.
AB  - Nanometer-scale proteinaceous pores are the basis of ion and macromolecular
      transport in cells and organelles. Recent studies suggest that ion channels and
      synthetic nanopores may prove useful in biotechnological applications. To better
      understand the structure-function relationship of nanopores, we are studying the
      ion-conducting properties of channels formed by wild-type and genetically
      engineered versions of Staphylococcus aureus alpha-hemolysin (alphaHL)
      reconstituted into planar lipid bilayer membranes. Specifically, we measured the
      ion selectivities and current-voltage relationships of channels formed with 24
      different alphaHL point cysteine mutants before and after derivatizing the
      cysteines with positively and negatively charged sulfhydryl-specific reagents.
      Novel negative charges convert the selectivity of the channel from weakly anionic
      to strongly cationic, and new positive charges increase the anionic selectivity.
      However, the extent of these changes depends on the channel radius at the
      position of the novel charge (predominantly affects ion selectivity) or on the
      location of these charges along the longitudinal axis of the channel (mainly
      alters the conductance-voltage curve). The results suggest that the net charge of
      the pore wall is responsible for cation-anion selectivity of the alphaHL channel
      and that the charge at the pore entrances is the main factor that determines the
      shape of the conductance-voltage curves.

PMID- 16085768
TI  - Actinic light-energy dependence of proton release from bacteriorhodopsin.
AB  - Measuring the light-density (fluence) dependence of proton release from flash
      excited bacteriorhodopsin with two independent methods we found that the lifetime
      of proton release increases and the proton pumping activity, defined as a number
      of protons per number of photocycle, decreases with increasing fluence. An
      interpretation of these results, based on bending of purple membrane and
      electrical interaction among the proton release groups of bacteriorhodopsin
      trimer, is presented.

PMID- 16085769
TI  - Mismatch-induced DNA unbending upon duplex opening.
AB  - A DNA duplex can be torn open at a specific position by introducing a branch or
      bulge to create an asymmetric three-way junction (TWJ). The opened duplex
      manifests a bent conformation (bending angle approximately 60 degrees , relative
      to the unopened form), which leads to a dramatic decrease in gel electrophoretic
      mobility. In the presence of a basepair mismatch at the opening position, the DNA
      backbone becomes less bent and assumes a distorted T-shaped structure, resulting
      in an increase in polyacrylamide gel electrophoretic mobility. Both
      conformational changes are confirmed using fluorescence resonance energy transfer
      experiments and found to be similar to the signature conformational changes of
      DNA duplex upon MutS protein binding. Our results imply that some structural
      rearrangements essential for mismatch recognition are achievable without protein
      interference. The gel electrophoretic mobility data for DNA TWJs with and without
      base mismatches correlates well with rotational diffusivity, computed by taking
      into account the conformational change of TWJ induced by base mismatch.

PMID- 16085770
TI  - 1,2-diacyl-phosphatidylcholine flip-flop measured directly by sum-frequency
      vibrational spectroscopy.
AB  - Sum-frequency vibrational spectroscopy (SFVS) is used to measure the intrinsic
      rate of lipid flip-flop for 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC),
      1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-distearoyl-sn-glycero
      3-phosphocholine (DSPC) in planar-supported lipid bilayers (PSs). Asymmetric
      PSLBs were prepared using the Langmuir-Blodgett/Langmuir-Schaefer method by
      placing a perdeuterated lipid analog in one leaflet of the PSLB. SFVS was used to
      directly measure the asymmetric distribution of the native lipid within the
      membrane by measuring the decay in the CH3 v(s) intensity at 2875 cm(-1) with
      time and as a function of temperature. An average activation energy of 220 kJ/mol
      for the translocation of DMPC, DPPC, and DSPC was determined. A decrease in alkyl
      chain length resulted in a substantial increase in the rate of flip-flop
      manifested as an increase in the Arrhenius preexponential factor. The effect of
      lipid labeling was investigated by measuring the exchange of 1,2-dipalmitoyl-sn
      glycero-3-phosphoethanolamine-n,n-Dimethyl-n-(2',2',6',6'-tetramethyl-4'
      piperidyl) (TEMPO-DPPC). The rate of TEMPO-DPPC flip-flop was an order-of
      magnitude slower compared to DPPC. An activation energy of 79 kJ/mol was measured
      which is comparable to that previously measured by electron spin resonance. The
      results of this study illustrate how SFVS can be used to directly measure lipid
      flip-flop without the need for a fluorescent or spin-labeled lipid probe, which
      can significantly alter the rate of lipid translocation.

PMID- 16085771
TI  - The hydroxylamine reaction of sensory rhodopsin II: light-induced conformational
      alterations with C13=C14 nonisomerizable pigment.
AB  - Sensory rhodopsin II, a repellent phototaxis receptor from Natronomonas
      (Natronobacterium) pharaonis (NpSRII), forms a complex with its cognate
      transducer (NpHtrII). In micelles the two proteins form a 1:1 heterodimer,
      whereas in membranes they assemble to a 2:2 complex. Similarly to other retinal
      proteins, sensory rhodopsin II undergoes a bleaching reaction with hydroxylamine
      in the dark which is markedly catalyzed by light. The reaction involves cleavage
      of the protonated Schiff base bond which covalently connects the retinal
      chromophore to the protein. The light acceleration reflects protein conformation
      alterations, at least in the retinal binding site, and thus allows for detection
      of these changes in various conditions. In this work we have followed the
      hydroxylamine reaction at different temperatures with and without the cognate
      transducer. We have found that light irradiation reduces the activation energy of
      the hydroxylamine reaction as well as the frequency factor. A similar effect was
      found previously for bacteriorhodopsin. The interaction with the transducer
      altered the light effect both in detergent and membranes. The transducer
      interaction decreased the apparent light effect on the energy of activation and
      the frequency factor in detergent but increased it in membranes. In addition, we
      have employed an artificial pigment derived from a retinal analog in which the
      critical C13=C14 double bond is locked by a rigid ring structure preventing its
      isomerization. We have observed light enhancement of the reaction rate and
      reduction of the energy of activation as well as the frequency factor, despite
      the fact that this pigment does not experience C13=C14 double bond isomerization.
      It is suggested that retinal excited state polarization caused by light
      absorption of the "locked" pigment polarizes the protein and triggers relatively
      long-lived protein conformational alterations.

PMID- 16085773
TI  - Single-molecule spectroscopic determination of lac repressor-DNA loop
      conformation.
AB  - The Escherichia coli lactose repressor protein (LacI) provides a classic model
      for understanding protein-induced DNA looping. LacI has a C-terminal four-helix
      bundle tetramerization domain that may act as a flexible hinge. In previous work,
      several DNA constructs, each containing two lac operators bracketing a sequence
      induced bend, were designed to stabilize different possible looping geometries.
      The resulting hyperstable LacI-DNA loops exist as both a compact "closed" form
      with a V-shaped repressor and also a more "open" form with an extended hinge. The
      "9C14" construct was of particular interest because footprinting, electrophoretic
      mobility shift, and ring closure experiments suggested that it forms both
      geometries. Previous fluorescence resonance energy transfer (FRET) measurements
      gave an efficiency of energy transfer (ET) of 70%, confirming the existence of a
      closed form. These measurements could not determine whether open form or
      intermediate geometries are populated or the timescale of interconversion. We
      have now applied single-molecule FRET to Cy3, Cy5 double-labeled LacI-DNA loops
      diffusing freely in solution. By using multiple excitation wavelengths and by
      carefully examining the behavior of the zero-ET peak during titration with LacI,
      we show that the LacI-9C14 loop exists exclusively in a single closed form
      exhibiting essentially 100% ET.

PMID- 16085772
TI  - Intracellular and extracellular concentrations of Na+ modulate Mg2+ transport in
      rat ventricular myocytes.
AB  - Apparent free cytoplasmic concentrations of Mg2+ ([Mg2+]i) and Na+ ([Na+]i) were
      estimated in rat ventricular myocytes using fluorescent indicators, furaptra (mag
      fura-2) for Mg2+ and sodium-binding benzofuran isophthalate for Na+, at 25
      degrees C in Ca2+-free conditions. Analysis included corrections for the
      influence of Na+ on furaptra fluorescence found in vitro and in vivo. The
      myocytes were loaded with Mg2+ in a solution containing 24 mM Mg2+ either in the
      presence of 106 mM Na+ plus 1 mM ouabain (Na+ loading) or in the presence of only
      1.6 mM Na+ to deplete the cells of Na+ (Na+ depletion). The initial rate of
      decrease in [Mg2+]i from the Mg2+-loaded cells was estimated in the presence of
      140 mM Na+ and 1 mM Mg2+ as an index of the rate of extracellular Na+-dependent
      Mg2+ efflux. Average [Na+]i, when estimated from sodium-binding benzofuran
      isophthalate fluorescence in separate experiments, increased from 12 to 31 mM and
      47 mM after Na+ loading for 1 and 3 h, respectively, and decreased to
      approximately 0 mM after 3 h of Na+ depletion. The intracellular Na+ loading
      significantly reduced the initial rate of decrease in [Mg2+]i, on average, by 40%
      at 1 h and by 64% at 3 h, suggesting that the Mg2+ efflux was inhibited by
      intracellular Na+ with 50% inhibition at approximately 40 mM. A reduction of the
      rate of Mg2+ efflux was also observed when Na+ was introduced into the cells
      through the amphotericin B-perforated cell membrane (perforated patch-clamp
      technique) via a patch pipette that contained 130 mM Na+. When the cells were
      heavily loaded with Na+ with ouabain in combination with intracellular perfusion
      from the patch pipette containing 130 mM Na+, removal of extracellular Na+ caused
      an increase in [Mg2+]i, albeit at a very limited rate, which could be interpreted
      as reversal of the Mg2+ transport, i.e., Mg2+ influx driven by reversed Na+
      gradient. Extracellular Na+ dependence of the rate of Mg2+ efflux revealed that
      the Mg2+ efflux was activated by extracellular Na+ with half-maximal activation
      at 55 mM. These results contribute to a quantitative characterization of the Na+
      Mg2+ exchange in cardiac myocytes.

PMID- 16085774
TI  - Cav1.4 encodes a calcium channel with low open probability and unitary
      conductance.
AB  - When transiently expressed in tsA-201 cells, Ca(v)1.4 calcium channels support
      only modest whole-cell currents with unusually slow voltage-dependent
      inactivation kinetics. To examine the basis for this unique behavior we used cell
      attached patch single-channel recordings using 100 mM external barium as the
      charge carrier to determine the single-channel properties of Ca(v)1.4 and to
      compare them to those of the Ca(v)1.2. Ca(v)1.4 channel openings occurred
      infrequently and were of brief duration. Moreover, openings occurred throughout
      the duration of the test depolarization, indicating that the slow inactivation
      kinetics observed at the whole-cell level are caused by sustained channel
      activity. Ca(v)1.4 and Ca(v)1.2 channels displayed similar latencies to first
      opening. Because of the rare occurrence of events, the probability of opening
      could not be precisely determined but was estimated to be <0.015 over a voltage
      range of -20 to +20 mV. The single-channel conductance of Ca(v)1.4 channels was
      approximately 4 pS compared with approximately 20 pS for Ca(v)1.2 under the same
      experimental conditions. Additionally, in the absence of divalent cations,
      Ca(v)1.4 channels pass cesium ions with a single-channel conductance of
      approximately 21 pS. Although Ca(v)1.2 opening events were best described
      kinetically with two open time constants, Ca(v)1.4 open times were best described
      by a single time constant. BayK8644 slightly enhanced the single-channel
      conductance in addition to increasing the open time constant for Ca(v)1.4
      channels by approximately 45% without, however, causing the appearance of an
      additional slower gating mode. Overall, our data indicate that single Ca(v)1.4
      channels support only minute amounts of calcium entry, suggesting that large
      numbers of these channels are needed to allow for significant whole-cell current
      activity, and providing a mechanism to reduce noise in the visual system.

PMID- 16085775
TI  - Variable incidence angle fluorescence interference contrast microscopy for z
      imaging single objects.
AB  - Surface-generated structured illumination microscopies interrogate the position
      of fluorescently labeled objects near surfaces with nanometer resolution along
      the z axis. However, these techniques are either experimentally cumbersome or
      applicable to a limited set of experimental systems. We present a new type of
      surface-generated structured illumination fluorescence microscopy, variable
      incidence angle fluorescence interference contrast microscopy (VIA-FLIC), in
      which the fluorescent sample is assembled above a reflective Si surface and the
      incidence angle of excitation light is varied by placing annular photomasks with
      different radii in the aperture diaphragm plane of the microscope. The variation
      in incidence angle alters the interference pattern of excitation light, and hence
      the intensity of detected fluorescence. Quantitative VIA-FLIC is tested by using
      a set of fluorophore-containing supported membranes separated from the Si surface
      by SiO2 layers of variable thicknesses. The resulting fluorescence intensity
      versus incidence angle curves depends on the separation from the Si surface and
      when fit with an appropriate model yield precise SiO2 thicknesses that are
      accurate with respect to the known SiO2 thicknesses. Since only a simple
      modification to a standard epifluorescence microscope is required, VIA-FLIC
      offers a versatile method to produce z-reconstructions with high resolution for a
      wide range of biological systems.

PMID- 16085777
TI  - On the kinetics of adsorption and two-dimensional self-assembly of annexin A5 on
      supported lipid bilayers.
AB  - Annexin A5 is a protein that binds to membranes containing negatively charged
      phospholipids in a calcium-dependent manner. We previously found that annexin A5
      self-assembles into two-dimensional (2D) crystals on supported lipid bilayers
      (SLBs) formed on mica while a monolayer of disordered trimers is formed on SLBs
      on silica. Here, we investigated in detail and correlated the adsorption kinetics
      of annexin A5 on SLBs, supported on silica and on mica, with the protein's 2D
      self-assembly behavior. For this study, quartz crystal microbalance with
      dissipation monitoring and ellipsometry were combined with atomic force
      microscopy. We find, in agreement with previous studies, that the adsorption
      behavior is strongly dependent on the concentration of dioleoylphosphatidylserine
      (DOPS) in the SLB and the calcium concentration in solution. The adsorption
      kinetics of annexin A5 are similar on silica-SLBs and on mica-SLBs, when taking
      into account the difference in accessible DOPS between silica-SLBs and mica-SLBs.
      In contrast, 2D crystals of annexin A5 form readily on mica-SLBs, even at low
      protein coverage (< or =10%), whereas they are not found on silica-SLBs, except
      in a narrow range close to maximal coverage. These results enable us to construct
      the phase diagram for the membrane binding and the states of 2D organization of
      annexin A5. The protein binds to the membrane in two different fractions, one
      reversible and the other irreversible, at a given calcium concentration. The
      adsorption is determined by the interaction of protein monomers with the
      membrane. We propose that the local membrane environment, as defined by the
      presence of DOPS, DOPC, and calcium ions, controls the adsorption and
      reversibility of protein binding.

PMID- 16085778
TI  - Mild cognitive impairment.

PMID- 16085776
TI  - Morphology of the lamellipodium and organization of actin filaments at the
      leading edge of crawling cells.
AB  - Lamellipodium extension, incorporating actin filament dynamics and the cell
      membrane, is simulated in three dimensions. The actin filament network topology
      and the role of actin-associated proteins such as Arp2/3 are examined. We find
      that the orientational pattern of the filaments is in accord with the
      experimental data only if the spatial orientation of the Arp2/3 complex is
      restricted during each branching event. We hypothesize that branching occurs when
      Arp2/3 is bound to Wiskott-Aldrich syndrome protein (WASP), which is in turn
      bound to Cdc42 signaling complex; Arp2/3 binding geometry is restricted by the
      membrane-bound complex. Using mechanical and energetic arguments, we show that
      any membrane protein that is conical or trapezoidal in shape preferentially
      resides at the curved regions of the plasma membrane. We hypothesize that the
      transmembrane receptors involved in the recruitment of Cdc42/WASP complex has
      this property and concentrate at the leading edge. These features, combined with
      the mechanical properties of the cell membrane, explain why lamellipodium is a
      flat organelle.

PMID- 16085779
TI  - Current epidemiology of mild cognitive impairment and other predementia
      syndromes.
AB  - A variety of clinically-defined predementia syndromes, with differing diagnostic
      criteria and nomenclature, have been proposed to describe nondisabling
      symptomatic cognitive deficits arising in elderly persons. Incidence and
      prevalence of different predementia syndromes vary as a result of different
      diagnostic criteria, sampling, and assessment procedures. The incidence rates of
      all predementia syndromes increase with age and are higher in subjects with less
      education; but age, educational background, and gender are not consistently
      related to prevalence rates. There is particular interest in "Mild Cognitive
      Impairment (MCI)" because this predementia syndrome is thought to be a prodromal
      phase of Alzheimer disease (AD). Several studies have suggested that most
      patients who meet MCI criteria will progress to AD, but rates of conversion to AD
      and dementia vary widely among studies. Furthermore, MCI definition is less
      consistent in population-based studies than clinical studies, in which
      progression to AD is also more consistent. To clarify the sources of discrepant
      findings in the literature, this review summarizes existing epidemiological
      studies of the defined clinical predementia syndromes and their progression to
      dementia.

PMID- 16085780
TI  - Mild cognitive impairment.
AB  - Mild cognitive impairment (MCI) describes a state of cognitive functioning that
      is below defined norms, yet falls short of dementia in severity. It exists across
      a cognitive continuum with borders that are difficult to define precisely. Within
      our "graying" western societies, its prevalence increases with age. A number of
      subtypes of MCI, including age-associated memory impairment (AAMI), age
      associated cognitive decline (AACD), amnestic MCI (MCIa), and cognitive
      impairment not dementia (CIND) have contributed to our understanding of MCI.
      Recent efforts have been directed at developing a uniform diagnostic
      classification for MCI that reflects the maturation of knowledge about this
      state. There is considerable etiological and clinical heterogeneity within MCI;
      however, there is a unifying increased risk of progression to dementia. The
      diagnostic process for MCI involves assessment of multiple cognitive domains,
      with particular attention to episodic and semantic memory, while neuroimaging
      with structural MRI and PET both add to the diagnostic and prognostic evaluation
      of MCI. Although there are no pharmacological treatments at present that are
      capable of delaying the long-term progression of MCI to dementia, there is some
      evidence of short-term symptomatic benefits with acetylcholinesterase inhibitors.
      MCI is an important clinical problem, which clinicians can expect to face with
      increasing frequency. The essentials of management include a thorough assessment
      directed at etiological determination and counseling and judicious use of
      available therapeutics.

PMID- 16085781
TI  - Population-based study of medical comorbidity in early dementia and "cognitive
      impairment, no dementia (CIND)": association with functional and cognitive
      impairment: The Cache County Study.
AB  - OBJECTIVE: Authors investigated medical comorbidity in persons with dementia and
      "Cognitive Impairment, No Dementia" (CIND). METHODS: The Cache County Study is an
      ongoing population-based study of the epidemiology of dementia, the risk factors
      for conversion from CIND to dementia, and the progression of dementia. As part of
      the study's first incidence wave, persons with dementia (N=149), CIND (N=225), or
      without cognitive impairment (N=321) were identified and studied. Participants
      received comprehensive clinical evaluations and were rated on the General Medical
      Health Rating (GMHR), a global measure of seriousness of medical comorbidity.
      Participants and informants also completed the Mini-Mental State Exam and
      provided self-report information about comorbid medical conditions and
      functioning in activities of daily living. RESULTS: There were few differences in
      number or type of comorbid medical conditions between persons with CIND and
      dementia, but persons with dementia were prescribed more medications. Stroke was
      more common in dementia participants, but other illnesses common in old age were
      not significantly different across cognitive groups. Medical comorbidity was more
      serious in both dementia and CIND, such that both groups were less likely to have
      "little to no" comorbidity. Seriousness of medical comorbidity was significantly
      associated with worse day-to-day functioning and cognition. CONCLUSIONS: Persons
      with CIND and dementia have more serious medical comorbidity than comparable
      persons without cognitive impairment. This comorbidity may play a role in the
      progression of CIND and dementia. Future studies should investigate the role of
      medical comorbidity and its treatment on dementia onset or progression, as well
      as the mechanisms mediating its neuropathologic effects.

PMID- 16085782
TI  - Subjective memory complaints, white-matter lesions, depressive symptoms, and
      cognition in elderly patients.
AB  - OBJECTIVES: Subjective memory complaints (SMC) and cerebral white-matter lesions
      (WML) are very prevalent among elderly subjects, but their clinical significance
      is controversial. The authors sought to determine whether SMCs are related to
      WML, independently of the presence of depressive symptoms, which are known to be
      associated with both. The relationship between SMC and cognition was also
      examined. METHODS: This is a cross-sectional study on 60 elderly subjects without
      dementia. All subjects underwent FLAIR and T2-weighted axial MRI scans, a memory
      complaint questionnaire, a geriatric depression scale, and a comprehensive
      cognitive assessment. RESULTS: Multiple linear regression showed that although
      the best correlate of SMC was the severity of depressive symptoms, SMC and WML
      were strongly correlated. Objective cognitive performance was not significantly
      associated with SMC after adjusting for WML and mood. The presence of a history
      of late-onset depression was a strong correlate of WML severity, even after
      adjusting for age, gender, and education. CONCLUSIONS: Complaints of cognitive
      decline are significantly associated with the severity of WML, independently of
      level of cognition and depression.

PMID- 16085783
TI  - Cognitive status, depressive symptoms, and health status as predictors of
      functional disability among elderly persons with low-to-moderate education: The
      Faenza Community Aging Study.
AB  - OBJECTIVE: The authors examined the impact of very early dementia and symptoms of
      depression on functional disability in a community-based group of 216 elderly
      people with low-to-moderate education level. METHODS: The combined effect of very
      early dementia and symptoms of depression on functional disability was assessed
      with a logistic-regression model in which functional disability was the dependent
      variable. The same model was repeated with each item on the Instrumental
      Activities of Daily Living scale as the dependent variable. RESULTS: Very early
      dementia alone was strongly associated with functional disability, and this
      association tripled in subjects with both very early dementia and symptoms of
      depression. In fact, whereas subjects with very early dementia had an 11-fold
      higher risk than normal persons for disability, subjects with both very early
      dementia and symptoms of depression showed a 37-fold higher risk for functional
      dependence. CONCLUSIONS: Elderly people who suffer from very early dementia and
      who also have symptoms of depression are at very high risk for functional
      disability and have a great need for accurate diagnostic assessment. If
      confirmed, the results are relevant for prevention because people who suffer from
      very early dementia and have symptoms of depression may be a suitable target
      group for intervention before the development of severe disability.

PMID- 16085784
TI  - Effects of anxiety versus depression on cognition in later life.
AB  - OBJECTIVE: The authors investigated the relationship between anxiety and
      cognition in older persons, taking account of comorbid depression. METHODS: Data
      were used from the Longitudinal Aging Study Amsterdam (LASA), a large
      epidemiological study of 3,107 elderly citizens in The Netherlands. Anxiety and
      depression were measured with the Hospital Anxiety and Depression Scale-Anxiety
      subscale and the Center for Epidemiologic Studies-Depression Scale. In measuring
      cognitive performance, general cognitive functioning was measured by means of
      Mini-Mental State Exam, episodic memory was measured with the Auditory Verbal
      Learning Test (AVLT), fluid intelligence by using the RAVEN, and information
      processing speed by the coding task. Analysis of variance examined the
      association between anxiety symptoms and cognition in persons with and without
      depression. RESULTS: Main effects of anxiety symptoms were found for learning and
      delayed recall of the AVLT. Depression symptoms showed significant main effects
      on almost all cognitive performance tests. Mild anxiety symptoms were associated
      with better cognitive performance, whereas severe anxiety symptoms were
      negatively associated with cognitive functioning. In contrast, depressive
      symptoms showed a linear association with cognition; more depression was
      associated with worse cognition. CONCLUSION: This study suggests that anxiety has
      a curvilinear relationship with cognition. Depressive symptoms, however, were
      always negatively associated with cognitive performance.

PMID- 16085785
TI  - Impact of cognitive impairment on the phenomenology of geriatric depression.
AB  - OBJECTIVE: Dementia and depressive syndromes demonstrate substantial symptom
      overlap. As a result, it is challenging to differentiate depression symptoms from
      nonspecific symptoms of an underlying dementia syndrome. The author addressed the
      impact of cognitive impairment on the phenomenology of depression symptoms by
      determining whether more impaired patients were more likely to endorse certain
      self-report depressive symptoms independent of their underlying level of
      depression severity. METHODS: Author used data from 576 geriatric rehabilitation
      inpatients for MIMIC model analyses examining the impact of cognitive impairment
      on both depression severity and endorsement of symptom clusters. Depressive
      symptoms were measured with the Geriatric Depression Scale, and cognitive
      impairment was measured with the Mattis Dementia Rating Scale total score.
      RESULTS: The reliability (internal consistency) of self-reported depressive
      symptoms did not change as a function of cognitive impairment. More severe
      cognitive impairment was associated with greater depression severity but was also
      associated with two depression symptom clusters after controlling for underlying
      levels of depression severity. Patients who were more impaired endorsed greater
      social withdrawal and less psychomotor agitation, independent of their underlying
      depression severity. Level of cognitive impairment alone did not affect the
      endorsement of depressed mood and positive affect. CONCLUSIONS: Certain symptoms
      on depression inventories may be endorsed at a greater level by cognitively
      impaired patients, independent of their level of underlying depression severity.
      These symptoms may be nonspecific features of the underlying dementia syndrome
      and may not be specific to depressive episodes, but instead may represent other
      syndromes, such as apathy.

PMID- 16085786
TI  - Increased risk of attempted suicide among aging holocaust survivors.
AB  - OBJECTIVE: Suicide rates are higher in elderly persons than in those at other
      phase of the life-cycle. The majority of World War II (WWII) veterans and
      Holocaust survivors still define their war experiences as being the "most
      significant stressor" of their lives. Aging of survivors is frequently associated
      with depression, reactivation of traumatic syndromes, physical disorders, loss,
      and psychological distress, possibly increasing the risk of suicide. The aim of
      the present study was to investigate, among a large cohort of elderly Holocaust
      survivors, whether their WWII experiences confer an increased risk of suicidal
      behavior. METHODS: All medical records of elderly patients admitted to a
      psychiatric hospital in Israel during a 5-year period were retrospectively
      evaluated. Suicidal patients were compared with patients who had not attempted
      suicide. RESULTS: Of 921 eligible patients, 374 were Holocaust survivors; 135
      (14.6%) had attempted suicide in the month before admission. Ninety Holocaust
      survivors (24%) had attempted suicide, versus 45 of the 502 patients (8.2%) with
      no WWII experience. The risk of attempted suicide among Holocaust survivors was
      significantly increased. CONCLUSION: Although these findings are from a highly
      selected sample, we suggest that aging Holocaust survivors are at increased risk
      of attempting suicide. The growth of the elderly population, of whom many had had
      traumatic life experiences, emphasizes the need to implement preventive
      strategies so that suicidal risk may be contained.

PMID- 16085787
TI  - Emotional impact of exposure to terrorism among young-old and old-old Israeli
      citizens.
AB  - OBJECTIVE: Since September 2000, continuous terrorist attacks have exposed
      Israeli society to trauma, and the impact of these events on the mental health of
      the elderly Israeli population remains unclear. The authors sought to assess the
      prevalence of posttraumatic stress-related symptoms of distress, depression,
      optimism, self-efficacy, and sense of safety of the young-old and old-old Jewish
      population after 19 months of intense terrorism in Israel, in order to identify
      correlates of the psychological sequelae and compare symptoms and coping methods
      of these populations with those of younger adults. METHODS: Authors did a
      telephone survey using stratified sampling with a national sample of young-old
      (65-74 years old), old-old (>74 years old) and a comparison group of younger
      adults (18-64 years old). RESULTS: No difference was found in the level of
      exposure, traumatic stress symptoms, including probable PTSD, except for a
      nonsignificant tendency toward more depersonalization and emotional numbness in
      the elderly group, a tendency toward more sleeplessness, more re-experiencing of
      unwanted thoughts, hyperarousal, fewer avoidance symptoms, and less disengagement
      coping in the old-old group. Younger adults were found to be significantly more
      optimistic. Young-old and old-old people used cigarettes/alcohol and
      tranquilizers more often to cope with the situation, and old-old people who used
      disengagement-coping felt less helped by it. CONCLUSIONS: Young-old and old-old
      people do not differ significantly from the younger adult population with regard
      to their response to 19 months of intense and recurrent terrorism.

PMID- 16085788
TI  - Predictors of partial remission in older patients treated for major depression:
      the role of comorbid dysthymia.
AB  - OBJECTIVE: The authors studied demographic, clinical, social, and perceived
      health and well-being factors as predictors of partial remission in older
      patients treated for major depressive disorder (MDD). METHODS: The sample
      included 186 patients who met DSM-IV criteria for MDD and underwent naturalistic
      treatment. Remission status was determined by Montgomery-Asberg Depression Rating
      Scale score. Ordinal logistic-regression was used to model the relationship
      between predictors and remission on an ordinal scale. RESULTS: A total of 26.9%
      patients were in partial remission (score: 7-15), and 25.8% were not in remission
      (score: 16-60) 1 year after the index evaluation. In bivariate analyses, the odds
      of partial/no remission were significantly increased for those with comorbid MDD
      and dysthymia and for those with higher baseline depression scores, and decreased
      for those with higher perceived social support. Other factors potentially
      associated with outcome included number of mobility/IADL limitations, perceived
      stress, self-perceived health, life dissatisfaction, and heart trouble.
      Controlling for these potential confounders, comorbid MDD and dysthymia
      significantly predicted outcome. The effect of mobility/IADL limitations differed
      for those with comorbid dysthymia. CONCLUSIONS: Among older adults treated for
      MDD, factors predicting partial remission appear to be similar to those
      predicting no remission. Patients with comorbid MDD and dysthymia are at
      increased risk for poor outcome, and predictors may vary by dysthymia status.

PMID- 16085789
TI  - Comparison of olanzapine and risperidone in the treatment of psychosis and
      associated behavioral disturbances in patients with dementia.
AB  - OBJECTIVE: The authors compared efficacy of olanzapine versus placebo and
      risperidone as measured by the Neuropsychiatric Inventory and Clinical Global
      Impression-Severity of Psychosis scale in patients with dementia-related
      psychosis. METHODS: Patients with moderate-to-severe psychotic symptoms
      associated with dementia were recruited from outpatient or residential settings
      and randomly assigned to 10-week, double-blind, flexible-dose treatment with
      olanzapine (N=204; 2.5 mg-10 mg/day; mean: 5.2 mg/day), risperidone (N=196; 0.5
      mg-2 mg/day; mean: 1.0 mg/day) or placebo (N=94). RESULTS: Most measures of
      neuropsychiatric functioning improved in all treatment groups, including the
      placebo group, and no significant treatment differences occurred. Overall
      discontinuation was lowest in the placebo group, and the olanzapine group had a
      significantly higher incidence of discontinuation due to adverse events (16.2%)
      relative to placebo (3.2%) and risperidone (8.7%) groups. Treatment-emergent
      extrapyramidal symptoms were more numerous for risperidone- than placebo- or
      olanzapine-treated patients. Abnormally high prolactin levels occurred in 78.0%
      of risperidone patients, compared with 16.7% for olanzapine and 5.0% for placebo.
      The incidence of weight gain greater than 7% from baseline was higher in the
      olanzapine group relative to risperidone, but neither active-treatment group
      showed a statistical difference from placebo (1.1%). No other statistically
      significant and clinically relevant differences were seen for any other vital
      sign, electrocardiographic measure, or laboratory hematology and chemistry,
      including glucose, except for cholesterol, which decreased from baseline to
      endpoint in both active-treatment groups. CONCLUSIONS: Patients' neuropsychiatric
      functioning improved with olanzapine, risperidone, and placebo treatment. There
      was a substantial response in the placebo group, and no significant differences
      emerged among treatments.

PMID- 16085790
TI  - Subjective memory complaints with and without objective memory impairment:
      relationship with risk factors for dementia.
AB  - OBJECTIVE: The authors investigated the frequency distribution of well
      established risk factors for dementia--high plasma homocysteine and the
      apolipoprotein E epsilon4 allele (APOE epsilon4)--among older women with
      subjective memory complaints (SMC) but no cognitive impairment, and with mild
      cognitive impairment (MCI). METHODS: This was a cross-sectional, community-based
      study. RESULTS: Women with MCI had higher total plasma homocysteine than healthy
      comparison subjects. There was also a nonsignificant excess of APOE epsilon4
      carriers in the MCI than in the healthy group. Participants with SMC had higher
      depression and anxiety scores than healthy-comparison subjects, but did not
      differ from subjects in the healthy-comparison group in relation to their total
      plasma homocysteine and APOE epsilon4 distribution. CONCLUSIONS: MCI seems to be
      more closely related to well-established risk factors for dementia than is SMC.

PMID- 16085791
TI  - Predicting cognitive decline in healthy older adults.
AB  - OBJECTIVE: Authors performed a neuropsychological determination of which
      individuals in a group of community-dwelling, healthy elderly volunteers would
      develop cognitive decline. METHODS: A group of 155 volunteers reporting good
      memory and thinking participated in a prospective study over 4 years. Authors
      monitored cognitive functioning and incidence of Mild Cognitive Impairment
      (MCI)/Alzheimer disease (AD). RESULTS: Baseline assessment revealed a subgroup of
      participants with deficits in associative learning and naming; subsequent
      cognitive decline was more precipitous in these individuals, who also showed
      higher relative risk of MCI/AD. CONCLUSION: Cognitive measures may be useful in
      community and clinical dementia screening and applicable for identifying enriched
      samples for trials of anti-dementia treatments.

PMID- 16085792
TI  - Expression of ATP-sensitive K+ channel subunits during perinatal maturation in
      the mouse heart.
AB  - Prevailing data suggest that sarcolemmal ATP-sensitive (K(ATP)) channels in the
      adult heart consist of Kir6.2 and SUR2A subunits, but the expression of other
      K(ATP) channel subunits (including SUR1, SUR2B, and Kir6.1) is poorly defined.
      The situation is even less clear for the immature heart, which shows a remarkable
      resistance to hypoxia and metabolic stress. The hypoxia-induced action potential
      shortening and opening of sarcolemmal K(ATP) channels that occurs in adults is
      less prominent in the immature heart. This might be due in part to the different
      biophysical and pharmacological properties of K(ATP) channels of immature and
      adult K(ATP) channels. Because these properties are largely conferred by subunit
      composition, it is important to examine the relative expression levels of the
      various K(ATP) channel subunits during maturation. We therefore used RNAse
      protection assays, reverse transcription-PCR approaches, and Western blotting to
      characterize the mRNA and protein expression profiles of K(ATP) channel subunits
      in fetal, neonatal, and adult mouse heart. Our data indicate that each of the
      K(ATP) channel subunits (Kir6.1, Kir6.2, SUR1, SUR2A, and SUR2B) is expressed in
      the mouse heart at all of the developmental time points studied. However, the
      expression level of each of the subunits is low in the fetal heart and
      progressively increases with maturation. Each of the subunits seems to be
      expressed in ventricular myocytes with a subcellular expression pattern matching
      that found in the adult. Our data suggest that the K(ATP) channel composition may
      change during maturation, which has important implications for K(ATP) channel
      function in the developing heart.

PMID- 16085794
TI  - Correlation of augmented IL-8 production to premature chronic lung disease:
      implication of posttranscriptional regulation.
AB  - Despite that advances in neonatal medicine have significantly reduced the early
      mortality of premature infants, a considerable number of them are still prone to
      develop chronic lung disease (CLD) later. To find a method of early prevention,
      we investigated the efficacy of using certain early proinflammatory responses to
      predict the development of CLD. In the present study, 34 premature infants who
      required endotracheal intubation within 4 h of birth were recruited for analysis
      of IL-8, IL-10, and TNF-alpha levels in their bronchoalveolar lavage (BAL) fluid
      and blood. It was found that level of IL-8 but not TNF-alpha or IL-10 in initial
      BAL fluid was significantly correlated to neutrophils in the BAL and inversely
      correlated to the gestational age of prematurity. Elevation of IL-8 level in BAL
      on the first day of life was correlated to the development of CLD. Further
      studies showed that neonatal cord blood released significantly higher IL-8 but
      lower TNF-alpha levels after stimulation by endotoxin. The augmented IL-8 mRNA
      expression in cord blood was inhibited by actinomycin D but enhanced by
      cycloheximide, suggesting that IL-8 production is controlled by de novo
      transcriptional induction as well as posttranscriptional up-regulation of IL-8 by
      neonatal leukocytes, relating to the development of CLD. Thus, an appropriate
      modulation of initial IL-8 production in premature infants might be beneficial
      for the prevention of the development of CLD.

PMID- 16085793
TI  - Long-chain polyunsaturated fatty acids modulate lung inflammatory response
      induced by Pseudomonas aeruginosa in mice.
AB  - Polyunsaturated fatty acid (PUFA) immunomodulatory properties have been studied
      extensively in chronic infections. Few studies have focused on acute infection;
      thus, PUFA effects in a mouse model of Pseudomonas aeruginosa (PA)-induced lung
      injury were evaluated. C57BL/6 mice were randomized to be fed for 3 wk with an
      eicosapentaenoic acid (EPA) diet, an arachidonic acid (AA) diet, or a control
      diet [saturated fatty acids]. Lung injury was induced by intratracheal
      instillation of 10(7) CFU of PA per mouse. In each diet group, animals were
      studied either without or after PA-inducing lung injury. Evaluation criteria were
      early mortality; inflammatory response assessed with tumor necrosis factor-alpha
      (TNF-alpha), IL-1beta, IL-6 and IL-10 levels in bronchoalveolar lavage; lung
      injury evaluation; and extravascular lung water, assessed 24 h after the injury.
      After PA-induced lung injury, no difference in early mortality was observed; TNF
      alpha level was significantly higher in the EPA diet than in the other two diet
      groups. No difference for the other cytokines was found among the groups. Lung
      edema was also more important in the EPA group, consistent with the variations of
      TNF-alpha levels. Our study clearly shows that in PA-induced acute lung injury, n
      3 PUFA induces differences in the inflammatory response with a higher level of
      lung edema. Modulation of the inflammatory response with n-3 PUFA can influence
      the response to a bacterial challenge.

PMID- 16085795
TI  - Defect of N-glycosylation is not directly related to congenital disorder of
      glycosylation Ia fibroblast sensitivity to staurosporine-induced cell death.
AB  - Congenital disorder of glycosylation Ia (CDGIa) is an autosomal recessive disease
      that is caused by mutations in the gene PMM2 encoding phosphomannomutase, an
      enzyme that synthesizes mannose-1-phosphate, an important intermediate for the N
      glycan biosynthesis. Here, we investigated the susceptibility of CDGIa
      fibroblasts to cell death induction. CDGIa fibroblasts were more sensitive than
      control fibroblasts to staurosporine-induced apoptosis. Supplementation with
      mannose, which corrects N-glycosylation in CDGIa fibroblasts, did not abrogate
      their higher sensitivity to staurosporine. These results show that the
      sensitivity of CDGIa fibroblasts to apoptosis is not directly related to their
      defective N-glycosylation.

PMID- 16085796
TI  - Kinetic modeling of plasma leucine levels during continuous venovenous
      extracorporeal removal therapy in neonates with maple syrup urine disease.
AB  - A kinetic modeling of leucine plasma concentration changes is proposed to
      describe the plasma leucine reduction rate during continuous extracorporeal
      removal therapy (CECRT) in neonates with maple syrup urine disease. Data were
      obtained from seven neonates using a bicompartmental model for the best fitted
      curve of plasma leucine decrease during CECRT. During the first 3 h, leucine
      plasma levels decreased according to an exponential curve: [Leu](t) = [Leu](i) x
      0.95 x 10(-0.09t) where [Leu](t) is the leucine plasma level (mumol/L) at time t
      (h) during CECRT and [Leu](I) is the initial plasma level. From h 4 to the end of
      CECRT, a second exponential curve was observed: [Leu](t) = [Leu](i) x 0.74 x 10(
      0.05t). Plasma leucine levels obtained from three other neonates were similar to
      those predicted by the model. The apparent distribution volumes for leucine that
      correspond to the two exponential equations obtained were calculated from the
      leucine mass removal collected in the spent dialysate and ultrafiltrate. The
      distribution volume was 34 +/- 3% of body weight during the first 3 h of CECRT
      and 72 +/- 7% from h 4 to the end of CECRT. These figures are similar to known
      values for the extracellular water compartment and for total body water in the
      newborn. The findings suggest that leucine handling during CECRT is similar to
      that of nonprotein-bound small-molecular-weight solutes such as urea.

PMID- 16085798
TI  - Microbial diversity and its relationship to planetary protection.

PMID- 16085799
TI  - Comparison between cultured small-intestinal and fecal microbiotas in beagle
      dogs.
AB  - The microbiota of the small intestine is poorly known because of difficulties in
      sampling. In this study, we examined whether the organisms cultured from the
      jejunum and feces resemble each other. Small-intestinal fluid samples were
      collected from 22 beagle dogs with a permanent jejunal fistula in parallel with
      fecal samples. In addition, corresponding samples from seven of the dogs were
      collected during a 4-week period (days 4, 10, 14, and 28) to examine the
      stability of the microbiota. In the jejunal samples, aerobic/facultative and
      anaerobic bacteria were equally represented, whereas anaerobes dominated in the
      fecal samples. Despite lower numbers of bacteria in the jejunum (range, 10(2) to
      10(6) CFU/g) than in feces (range, 10(8) to 10(11) CFU/g), some microbial groups
      were more prevalent in the small intestine: staphylococci, 64% versus 36%;
      nonfermentative gram-negative rods, 27% versus 9%; and yeasts, 27% versus 5%,
      respectively. In contrast, part of the fecal dominant microbiota (bile-resistant
      Bacteroides spp., Clostridium hiranonis-like organisms, and lactobacilli) was
      practically absent in the jejunum. Many species were seldom isolated
      simultaneously from both sample types, regardless of their overall prevalence. In
      conclusion, the small intestine contains a few bacterial species at a time with
      vastly fluctuating counts, opposite to the results obtained for the colon, where
      the major bacterial groups remain relatively constant over time. Qualitative and
      quantitative differences between the corresponding jejunal and fecal samples
      indicate the inability of fecal samples to represent the microbiotas present in
      the upper gut.

PMID- 16085800
TI  - Halotolerant cyanobacterium Aphanothece halophytica contains NapA-type Na+/H+
      antiporters with novel ion specificity that are involved in salt tolerance at
      alkaline pH.
AB  - Aphanothece halophytica is a halotolerant alkaliphilic cyanobacterium which can
      grow at NaCl concentrations up to 3.0 M and at pH values up to 11. The genome
      sequence revealed that the cyanobacterium Synechocystis sp. strain PCC 6803
      contains five putative Na+/H+ antiporters, two of which are homologous to NhaP of
      Pseudomonas aeruginosa and three of which are homologous to NapA of Enterococcus
      hirae. The physiological and functional properties of NapA-type antiporters are
      largely unknown. One of NapA-type antiporters in Synechocystis sp. strain PCC
      6803 has been proposed to be essential for the survival of this organism. In this
      study, we examined the isolation and characterization of the homologous gene in
      Aphanothece halophytica. Two genes encoding polypeptides of the same size,
      designated Ap-napA1-1 and Ap-napA1-2, were isolated. Ap-NapA1-1 exhibited a
      higher level of homology to the Synechocystis ortholog (Syn-NapA1) than Ap-NapA1
      2 exhibited. Ap-NapA1-1, Ap-NapA1-2, and Syn-NapA1 complemented the salt
      sensitive phenotypes of an Escherichia coli mutant and exhibited strongly pH
      dependent Na+/H+ and Li+/H+ exchange activities (the highest activities were at
      alkaline pH), although the activities of Ap-NapA1-2 were significantly lower than
      the activities of the other polypeptides. Only one these polypeptides, Ap-NapA1
      2, complemented a K+ uptake-deficient E. coli mutant and exhibited K+ uptake
      activity. Mutagenesis experiments suggested the importance of Glu129, Asp225, and
      Asp226 in the putative transmembrane segment and Glu142 in the loop region for
      the activity. Overexpression of Ap-NapA1-1 in the freshwater cyanobacterium
      Synechococcus sp. strain PCC 7942 enhanced the salt tolerance of cells,
      especially at alkaline pH. These findings indicate that A. halophytica has two
      NapA1-type antiporters which exhibit different ion specificities and play an
      important role in salt tolerance at alkaline pH.

PMID- 16085801
TI  - Inhibition of Clostridium perfringens by a novel strain of Bacillus subtilis
      isolated from the gastrointestinal tracts of healthy chickens.
AB  - The objectives of this study were to isolate beneficial strains of microorganisms
      from the gastrointestinal tracts of healthy chickens and to screen them against
      Clostridium perfringens, a causative agent of necrotic enteritis in poultry. One
      of the bacteria isolated, a strain of Bacillus subtilis, was found to possess an
      anticlostridial factor that could inhibit the C. perfringens ATCC 13124 used in
      this study. The anticlostridial factor produced by B. subtilis PB6 was found to
      be fully or partially inactivated in the presence of pronase, trypsin, and
      pepsin. In contrast, the antimicrobial activity of the anticlostridial factor was
      not affected by treatment at 100 or 121 degrees C or by treatment with any of the
      organic solvents used in the study. The optimum growth temperature and optimum pH
      for production of the anticlostridial factor were 37 degrees C and 6.20,
      respectively. Using the mass spectroscopy-mass spectroscopy technique, the
      apparent molecular mass of the anticlostridial factor was estimated to be in the
      range from 960 to 983 Da. In terms of the antimicrobial spectrum, the
      anticlostridial factor was inhibitory toward various strains of C. perfringens
      implicated in necrotic enteritis in poultry, Clostridium difficile, Streptococcus
      pneumoniae, Campylobacter jejuni, and Campylobacter coli.

PMID- 16085802
TI  - Integration of signals through Crc and PtsN in catabolite repression of
      Pseudomonas putida TOL plasmid pWW0.
AB  - Toluene degradation in Pseudomonas putida KT2440 pWW0 plasmid is subjected to
      catabolite repression. Pu and P(S1) promoters of the pWW0 TOL plasmid are down
      regulated in vivo during exponential growth in rich medium. In cells growing on
      minimal medium, yeast extract (YE) addition mimics exponential-phase rich medium
      repression of these promoters. We have constructed and tested mutants in a series
      of global regulators described in Pseudomonas. We describe that a mutant in crc
      (catabolite repression control) partially relieves YE repression. Macroarray
      experiments show that crc transcription is strongly increased in the presence of
      YE, inversely correlated with TOL pathway expression. On the other hand, we have
      found that induced levels of expression from Pu and P(S) in the presence of YE
      are partially derepressed in a ptsN mutant of P. putida. PtsN but not Crc seems
      to directly interfere with XylR activation at target promoters. The effect of the
      double mutation in ptsN and crc is not the sum of the effects of each independent
      mutation and suggests that both regulators are elements of a common regulatory
      pathway. Basal expression levels from these promoters in the absence of inducer
      are still XylR dependent and are also repressed in the presence of yeast extract.
      Neither crc nor ptsN could relieve this repression.

PMID- 16085803
TI  - Metabolism of the aliphatic nitramine 4-nitro-2,4-diazabutanal by
      Methylobacterium sp. strain JS178.
AB  - The aliphatic nitramine 4-nitro-2,4-diazabutanal (NDAB; C2H5N3O3) is a ring
      cleavage metabolite that accumulates during the aerobic degradation of the
      energetic compound hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by various
      Rhodococcus spp. NDAB is also produced during the alkaline hydrolysis of either
      RDX or octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and during the
      photolysis of RDX. Traces of NDAB were observed in a soil sampled from an
      ammunition-manufacturing facility contaminated with both HMX and RDX, suggesting
      natural attenuation. In this study, we report the isolation of a soil bacterium
      that is able to degrade NDAB under aerobic conditions. The isolate is a pink
      pigmented facultative methylotroph affiliated with the genus Methylobacterium.
      The strain, named Methylobacterium sp. strain JS178, degrades NDAB as a sole
      nitrogen source, with concomitant growth and formation of 1 molar equivalent of
      nitrous oxide (N2O). Comparison of the growth yield of strain JS178 grown on
      NDAB, nitrite (NO2-), or ammonium (NH4+) as a nitrogen source revealed that 1 N
      equivalent is assimilated from each mole of NDAB, which completes the nitrogen
      mass balance. In radiotracer experiments, strain JS178 mineralized 1 C of the
      [14C]NDAB produced in situ from [14C]RDX by Rhodococcus sp. strain DN22. Studies
      on the regulation of NDAB degradation indicated that allantoin, an intermediate
      in the purine catabolic pathway and a central molecule in the storage and
      transport of nitrogen in plants, up-regulated the enzyme(s) involved in the
      degradation of the nitramine. The results reveal the potential for the sequential
      participation of rhodococci and methylobacteria to effect the complete
      degradation of RDX.

PMID- 16085805
TI  - Development and assessment of a real-time pcr assay for rapid and sensitive
      detection of a novel thermotolerant bacterium, Lactobacillus thermotolerans, in
      chicken feces.
AB  - A new real-time PCR assay was successfully developed using a TaqMan fluorescence
      probe for specific detection and enumeration of a novel bacterium, Lactobacillus
      thermotolerans, in chicken feces. The specific primers and probe were designed
      based on the L. thermotolerans 16S rRNA gene sequences, and these sequences were
      compared to those of all available 16S rRNA genes in the GenBank database. The
      assay, targeting 16S rRNA gene, was evaluated using DNA from a pure culture of L.
      thermotolerans, DNA from the closely related bacteria Lactobacillus mucosae DSM
      13345(T) and Lactobacillus fermentum JCM 1173(T), and DNA from other lactic acid
      bacteria in quantitative experiments. Serial dilutions of L. thermotolerans DNA
      were used as external standards for calibration. The minimum detection limit of
      this technique was 1.84 x 10(3) cells/ml of an L. thermotolerans pure culture.
      The assay was then applied to chicken feces in two different trials. In the first
      trial, the cell population was 10(4) cells/g feces on day 4 and 10(5) cells/g
      feces on days 11 to 18. However, cell populations of 10(6) to 10(7) cells/g feces
      were detected in the second trial. The total bacterial count, measured by 4',6
      diamidino-2-phenylindole (DAPI) staining, was approximately 10(11) cells/g feces.
      These results suggest that in general, L. thermotolerans is a normal member of
      the chicken gut microbiota, although it is present at relatively low levels in
      the feces.

PMID- 16085804
TI  - Impact of plant species and site on rhizosphere-associated fungi antagonistic to
      Verticillium dahliae kleb.
AB  - Fungi with antagonistic activity toward plant pathogens play an essential role in
      plant growth and health. To analyze the effects of the plant species and the site
      on the abundance and composition of fungi with antagonistic activity toward
      Verticillium dahliae, fungi were isolated from oilseed rape and strawberry
      rhizosphere and bulk soil from three different locations in Germany over two
      growing seasons. A total of 4,320 microfungi screened for in vitro antagonism
      toward Verticillium resulted in 911 active isolates. This high proportion of
      fungi antagonistic toward the pathogen V. dahliae was found for bulk and
      rhizosphere soil at all sites. A plant- and site-dependent specificity of the
      composition of antagonistic morphotypes and their genotypic diversity was found.
      The strawberry rhizosphere was characterized by preferential occurrence of
      Penicillium and Paecilomyces isolates and low numbers of morphotypes (n = 31) and
      species (n = 13), while Monographella isolates were most frequently obtained from
      the rhizosphere of oilseed rape, for which higher numbers of morphotypes (n = 41)
      and species (n = 17) were found. Trichoderma strains displayed high diversity in
      all soils, but a high degree of plant specificity was shown by BOX-PCR
      fingerprints. The diversity of rhizosphere-associated antagonists was lower than
      that of antagonists in bulk soil, suggesting that some fungi were specifically
      enriched in each rhizosphere. A broad spectrum of new Verticillium antagonists
      was identified, and the implications of the data for biocontrol applications are
      discussed.

PMID- 16085806
TI  - Use of enrichment culture for directed evolution of the Vibrio fluvialis JS17
      omega-transaminase, which is resistant to product inhibition by aliphatic
      ketones.
AB  - A novel high-throughput screening method that overcame product inhibition was
      used to isolate a mutant omega-transaminase from Vibrio fluvialis JS17. An enzyme
      library was generated using error-prone PCR mutagenesis and then enriched on
      minimal medium containing 2-aminoheptane as the sole nitrogen source and 2
      butanone as an inhibitory ketone. An identified mutant enzyme, omega-TAmla,
      showed significantly reduced product inhibition by aliphatic ketone. The product
      inhibition constants of the mutant with 2-butanone and 2-heptanone were 6- and
      4.5-fold higher than those of the wild type, respectively. Using omega-TAmla (50
      U/ml) overexpressed in Escherichia coli BL21, 150 mM 2-aminoheptane was
      successfully resolved to (R)-2-aminoheptane (enantiomeric excess, >99%) with 53%
      conversion with an enantioselectivity of >100.

PMID- 16085808
TI  - Study of adhesion and survival of lactobacilli and bifidobacteria on table olives
      with the aim of formulating a new probiotic food.
AB  - With the aim of developing new functional foods, a traditional product, the table
      olive, was used as a vehicle for incorporating probiotic bacterial species.
      Survival on table olives of Lactobacillus rhamnosus (three strains),
      Lactobacillus paracasei (two strains), Bifidobacterium bifidum (one strain), and
      Bifidobacterium longum (one strain) at room temperature was investigated. The
      results obtained using a selected olive sample demonstrated that bifidobacteria
      and one strain of L. rhamnosus (Lactobacillus GG) showed a good survival rate,
      with a recovery of about 10(6) CFU g(-1) after 30 days. The Lactobacillus GG
      population remained unvaried until the end of the experiment, while a slight
      decline (to about 10(5) CFU g(-1)) was observed for bifidobacteria. High
      viability, with more than 10(7) CFU g(-1), was observed throughout the 3-month
      experiment for L. paracasei IMPC2.1. This strain, selected for its potential
      probiotic characteristics and for its lengthy survival on olives, was used to
      validate table olives as a carrier for transporting bacterial cells into the
      human gastrointestinal tract. L. paracasei IMPC2.1 was recovered from fecal
      samples in four out of five volunteers fed 10 to 15 olives per day carrying about
      10(9) to 10(10) viable cells for 10 days.

PMID- 16085807
TI  - Characterization of an unusual cold-active beta-glucosidase belonging to family 3
      of the glycoside hydrolases from the psychrophilic isolate Paenibacillus sp.
      strain C7.
AB  - We selected for spore-forming psychrophilic bacteria able to use lactose as a
      carbon source and one isolate, designated Paenibacillus sp. strain C7, that was
      phylogenetically related to, but distinct from both Paenibacillus macquariensis
      and Paenibacillus antarcticus. Some Escherichia coli transformants obtained with
      genomic DNA from this isolate hydrolyzed X-Gal (5-bromo-4-chloro-3-indoyl-beta-D
      galactopyranoside) only below 30 degrees C, an indication of cold-active beta
      galactosidase activity. Sequencing of the cloned insert revealed an open reading
      frame encoding a 756-amino acid protein that, rather than belonging to a family
      typically known for beta-galactosidase activity, belonged to glycoside hydrolase
      family 3, a family of beta-glucosidases. Because of this unusual placement, the
      recombinant enzyme (BglY) was purified and characterized. Consistent with its
      classification, the enzyme had seven times greater activity with the glucoside
      substrate ONPGlu (o-nitrophenyl-beta-D-glucopyranoside) than with the galactoside
      substrate ONPGal (o-nitrophenyl-beta-D-galactopyranoside). In addition, the
      enzyme had, with ONPGlu, a thermal optimum around 30 to 35 degrees C, activity
      over a broad pH range (5.5 to 10.9), and an especially low Km (<0.003 mM).
      Further examination of substrate preference showed that the BglY enzyme also
      hydrolyzed other aryl-beta-glucosides such as helicin, MUG (4-methylumbelliferyl
      beta-D-glucopyranoside), esculin, indoxyl-beta-D-glucoside (a natural indigo
      precursor), and salicin, but had no activity with glucosidic disaccharides or
      lactose. These characteristics and substrate preferences make the BglY enzyme
      unique among the family 3 beta-glucosidases. The hydrolysis of a variety of aryl
      beta-glucosides suggests that the enzyme may allow the organism to use these
      substrates in the environment and that its low Km on indoxyl-beta-D-glucoside may
      make it useful for producing indigo.

PMID- 16085809
TI  - Role for HtrA in stress induction and virulence potential in Listeria
      monocytogenes.
AB  - In silico analysis of the Listeria monocytogenes genome revealed lmo0292, a gene
      predicted to encode a HtrA-like serine protease. A stable insertion mutant was
      constructed, revealing a requirement for htrA in the listerial response to heat,
      acid, and penicillin stress. Transcriptional analysis revealed that htrA is not
      induced in response to heat shock but is induced in response to low pH and
      penicillin G stress. Furthermore, htrA expression was shown to be dependent upon
      the LisRK two-component sensor-kinase, a system known to respond to changes in
      integrity of the cell envelope. In addition, we demonstrated that a second in
      frame start codon, upstream of that previously annotated for L. monocytogenes
      htrA, incorporating a putative signal sequence appears to influence virulence
      potential. Finally, a significant virulence defect was observed for the htrA
      mutant, indicating that this gene is required for full virulence in mice. Our
      findings suggest that L. monocytogenes lmo0292 encodes an HtrA-like serine
      protease that is not part of the classical heat shock response but is involved in
      stress responses and virulence.

PMID- 16085810
TI  - Naturally occurring DNA transfer system associated with membrane vesicles in
      cellulolytic Ruminococcus spp. of ruminal origin.
AB  - A genetic transformation system with similarities to those reported for gram
      negative bacteria was found to be associated with membrane vesicles of the
      ruminal cellulolytic genus Ruminococcus. Double-stranded DNA was recovered from
      the subcellular particulate fraction of all the cellulolytic ruminococci
      examined. Electron microscopy revealed that the only particles present resembled
      membrane vesicles. The likelihood that the DNA was associated with membrane
      vesicles (also known to contain cellulosomes) was further supported by the
      adherence of the particles associated with the subcellular DNA to cellulose
      powder added to culture filtrates. The particle-associated DNA comprised a
      population of linear molecules ranging in size from <20 kb to 49 kb (Ruminococcus
      sp. strain YE73) and from 23 kb to 90 kb (Ruminococcus albus AR67). Particle
      associated DNA from R. albus AR67 represented DNA derived from genomic DNA of the
      host bacterium having an almost identical HindIII digestion pattern and an
      identical 16S rRNA gene. Paradoxically, particle-associated DNA was refractory to
      digestion with EcoRI, while the genomic DNA was susceptible to extensive
      digestion, suggesting that there is differential restriction modification of
      genomic DNA and DNA exported from the cell. Transformation using the vesicle
      containing fraction of culture supernatant of Ruminococcus sp. strain YE71 was
      able to restore the ability to degrade crystalline cellulose to two mutants that
      were otherwise unable to do so. The ability was heritable and transferred to
      subsequent generations. It appears that membrane-associated transformation plays
      a role in lateral gene transfer in complex microbial ecosystems, such as the
      rumen.

PMID- 16085811
TI  - Functional importance of deletion mutant genotypes in an insect
      nucleopolyhedrovirus population.
AB  - A Nicaraguan isolate of a nucleopolyhedrovirus (SfNIC) that attacks the fall
      armyworm, Spodoptera frugiperda, survives as a mixture of nine genotypes (SfNIC A
      to I) that all present genomic deletions, except variant B (complete genotype).
      Sequencing of cloned restriction fragments revealed that genotypic variants lack
      between 5 and 16 of the open reading frames present in a contiguous sequence of
      18 kb of the SfNIC genome. The absence of oral infectivity of SfNIC-C and -D
      variants is related to the deletion of the pif and/or pif-2 gene, while that of
      SfNIC-G remains unexplained. The presence of open reading frame 10, homolog of
      Se030, also appeared to influence pathogenicity in certain variants. Previous
      studies demonstrated a significant positive interaction between genotypes B and
      C. We compared the median lethal concentration of single genotypes (A, B, C, D,
      and F) and co-occluded genotype mixtures (B+A, B+D, B+F, A+C, and F+C in a 3:1
      ratio). Mixtures B+A and B+D showed increased pathogenicity, although only B+D
      restored the activity of the mixture to that of the natural population. Mixtures
      of two deletion variants (A+C and F+C) did not show interactions in
      pathogenicity. We conclude that minority genotypes have an important influence on
      the overall pathogenicity of the population. These results clearly demonstrate
      the value of retaining genotypic diversity in virus-based bioinsecticides.

PMID- 16085812
TI  - Simultaneous display of multiple foreign peptides in the FliD capping and FliC
      filament proteins of the Escherichia coli flagellum.
AB  - The bacterial flagellum is composed of more than 20 different proteins. The
      filament, which constitutes the major extracellular part of the flagellum, is
      built up of approximately 20,000 FliC molecules that assemble at the growing
      distal end of the filament. A capping structure composed of five FliD molecules
      located at the tip of the filament promotes polymerization of FliC. Lack of FliD
      leads to release of the subunits into the growth medium. We show here that FliD
      can be successfully used in bacterial surface display. We tested various
      insertion sites in the capping protein, and the optimal region for display was at
      the variable region in FliD. Deletion and/or insertion at other sites resulted in
      decreased formation of flagella. We further developed the technique into a
      multihybrid display system in which three foreign peptides are simultaneously
      expressed within the same flagellum, i.e., D repeats of FnBPA from Staphylococcus
      aureus at the tip and fragments of YadA from Yersinia enterocolitica as well as
      SlpA from Lactobacillus crispatus along the filament. This technology can have
      biotechnological applications, e.g., in simultaneous delivery of several effector
      molecules.

PMID- 16085813
TI  - Bacteriophages may bias outcome of bacterial enrichment cultures.
AB  - Enrichment cultures are widely used for the isolation of bacteria in clinical,
      biotechnological, and environmental studies. However, competition, relative
      growth rates, or inhibitory effects may alter the outcome of enrichment cultures,
      causing the phenomenon known as enrichment bias. Bacteriophages are a major
      component in many microbial systems, and it abounds in natural settings. This
      abundance means that bacteriophages are likely to be present in many laboratory
      enrichment cultures. Our hypothesis was that bacteriophages present in the sample
      might bias the enriched subpopulation, since it can infect and lyse the target
      bacteria during the enrichment step once the bacteria reach a given density. Here
      we show that the presence of bacteriophages in Salmonella and Shigella enrichment
      cultures produced a significant reduction (more than 1 log unit) in the number of
      these bacteria compared with samples in which bacteriophages had been reduced by
      filtration through 0.45-microm non-protein-binding membranes. Furthermore, our
      data indicate that the Salmonella biotypes isolated after the enrichment culture
      change if bacteriophages are present, thus distorting the results of the
      analysis.

PMID- 16085814
TI  - Diel infection of a cyanobacterium by a contractile bacteriophage.
AB  - Light was found to strongly influence the infection of a freshwater
      cyanobacterium (Synechococcus elongatus PCC 7942) by a contractile DNA phage
      named AS-1. Phage progeny production was correlated with the amount of light in
      the laboratory and occurred in a diel pattern under natural light. At least one
      effect of light on AS-1 infection is at the level of adsorption.

PMID- 16085815
TI  - Correlation of biological activity and reactor performance in biofiltration of
      toluene with the fungus Paecilomyces variotii CBS115145.
AB  - A biofiltration system inoculated with the mold Paecilomyces variotii CBS115145
      showed a toluene elimination capacity (EC) of around 250 g/m3 of biofilter/h,
      which was higher than the values usually reported for bacteria. P. variotii
      assimilated m- and p-cresols but not the o isomer. Initial toluene hydroxylation
      occurred both on the methyl group and through the p-cresol pathway. These results
      were corroborated by detecting benzyl alcohol, benzaldehyde, and p-cresol as
      volatile intermediates. In liquid cultures with toluene as a substrate, the
      activity of toluene oxygenase (TO) was 5.6 nmol of O2/min/mg of biomass, and that
      of benzyl alcohol dehydrogenase was 16.2 nmol of NADH/min/mg of protein. Toluene
      biodegradation determined from the TO activity in the biofilter depended on the
      biomass distribution and the substrate concentration. The specific enzymatic
      activity decreased from 6.3 to 1.9 nmol of O2/min/mg of biomass along the
      reactor. Good agreement was found between the EC calculated from the TO activity
      and the EC measured on the biofilter. The results were confirmed by short-time
      biofiltration experiments. Average EC measured in different biofiltration
      experiments and EC calculated from the TO activity showed a linear relation,
      suggesting that in the biofilters, EC was limited by biological reaction. As the
      enzymatic activities of P. variotii were similar to those reported for bacteria,
      the high performance of the fungal biofilters can possibly be explained by the
      increased transfer of the hydrophobic compounds, including oxygen, from the gas
      phase to the mycelia, overcoming the transfer problems associated with the flat
      bacterial biofilms.

PMID- 16085816
TI  - Elucidation of a carotenoid biosynthesis gene cluster encoding a novel enzyme,
      2,2'-beta-hydroxylase, from Brevundimonas sp. strain SD212 and combinatorial
      biosynthesis of new or rare xanthophylls.
AB  - A carotenoid biosynthesis gene cluster mediating the production of 2
      hydroxyastaxanthin was isolated from the marine bacterium Brevundimonas sp.
      strain SD212 by using a common crtI sequence as the probe DNA. A sequence
      analysis revealed this cluster to contain 12 open reading frames (ORFs),
      including the 7 known genes, crtW, crtY, crtI, crtB, crtE, idi, and crtZ. The
      individual ORFs were functionally analyzed by complementation studies using
      Escherichia coli that accumulated various carotenoid precursors due to the
      presence of other bacterial crt genes. In addition to functionally identifying
      the known crt genes, we found that one (ORF11, named crtG) coded for a novel
      enzyme, carotenoid 2,2'-beta-hydroxylase, which showed intriguingly partial
      homology with animal sterol-C5-desaturase. When this crtG gene was introduced
      into E. coli accumulating zeaxanthin and canthaxanthin, the resulting
      transformants produced their 2-hydroxylated and 2,2'-dihydroxylated products
      which were structurally novel or rare xanthophylls, as determined by their
      nuclear magnetic resonance and high-performance liquid chromatography/photodiode
      array detector/atmospheric pressure chemical ionization mass spectrometry
      spectral data. The new carotenoid produced was suggested to have a strong
      inhibitory effect on lipid peroxidation.

PMID- 16085817
TI  - Expression of 3-ketoacyl-acyl carrier protein reductase (fabG) genes enhances
      production of polyhydroxyalkanoate copolymer from glucose in recombinant
      Escherichia coli JM109.
AB  - Polyhydroxyalkanoates (PHAs) are biologically produced polyesters that have
      potential application as biodegradable plastics. Especially important are the
      short-chain-length-medium-chain-length (SCL-MCL) PHA copolymers, which have
      properties ranging from thermoplastic to elastomeric, depending on the ratio of
      SCL to MCL monomers incorporated into the copolymer. Because of the potential
      wide range of applications for SCL-MCL PHA copolymers, it is important to develop
      and characterize metabolic pathways for SCL-MCL PHA production. In previous
      studies, coexpression of PHA synthase genes and the 3-ketoacyl-acyl carrier
      protein reductase gene (fabG) in recombinant Escherichia coli has been shown to
      enhance PHA production from related carbon sources such as fatty acids. In this
      study, a new fabG gene from Pseudomonas sp. 61-3 was cloned and its gene product
      characterized. Results indicate that the Pseudomonas sp. 61-3 and E. coli FabG
      proteins have different substrate specificities in vitro. The current study also
      presents the first evidence that coexpression of fabG genes from either E. coli
      or Pseudomonas sp. 61-3 with fabH(F87T) and PHA synthase genes can enhance the
      production of SCL-MCL PHA copolymers from nonrelated carbon sources. Differences
      in the substrate specificities of the FabG proteins were reflected in the monomer
      composition of the polymers produced by recombinant E. coli. SCL-MCL PHA
      copolymer isolated from a recombinant E. coli strain had improved physical
      properties compared to the SCL homopolymer poly-3-hydroxybutyrate. This study
      defines a pathway to produce SCL-MCL PHA copolymer from the fatty acid
      biosynthesis that may impact on PHA production in recombinant organisms.

PMID- 16085818
TI  - Effects of bacteria on Artemia franciscana cultured in different gnotobiotic
      environments.
AB  - The use of probiotics is receiving considerable attention as an alternative
      approach to control microbiota in aquaculture farms, especially in hatching
      facilities. However, application with consistent results is hampered by
      insufficient information on their modes of action. To investigate whether dead
      bacteria (allowing investigation of their nutritional effect) or live bacteria
      (allowing evaluation of their probiotic effect) have any beneficial effect
      towards Artemia franciscana and, subsequently, if live bacteria have probiotic
      effects beyond the effects observed with dead bacteria, a model system was
      employed using gnotobiotic Artemia as a test organism. Nauplii were cultured in
      the presence of 10 bacterial strains combined with four different major axenic
      live feeds (two strains of Saccharomyces cerevisiae and two strains of Dunaliella
      tertiolecta) differing in their nutritional values. In combination with poor- and
      medium-quality live feeds, dead bacteria exerted a strong effect on Artemia
      survival but a rather weak or no effect on individual length and constituted a
      maximum of only 5.9% of the total ash-free dry weight supplied. These effects
      were reduced or even disappeared when medium- to good-quality major feed sources
      were used, possibly due to improvements in the health status of Artemia. Some
      probiotic bacteria, such as GR 8 (Cytophaga spp.), improved (not always
      significantly) the performance of nauplii beyond the effect observed with dead
      bacteria, independently of the feed supplied. The present approach can be an
      excellent system to study the exact mode of action of bacteria, especially if
      combined with challenge tests or other types of analysis (e.g., transcriptome and
      proteonomic analysis).

PMID- 16085819
TI  - Discrimination of enterobacterial repetitive intergenic consensus PCR types of
      Campylobacter coli and Campylobacter jejuni by Fourier transform infrared
      spectroscopy.
AB  - Fourier transform infrared spectroscopy (FT-IR) has been used together with
      pattern recognition methodology to study isolates belonging to the species
      Campylobacter coli and Campylobacter jejuni and to compare FT-IR typing schemes
      with established genomic profiles based on enterobacterial repetitive intergenic
      consensus PCR (ERIC-PCR). Seventeen isolates were cultivated under standardized
      conditions for 2, 3, and 4 days to study variability and improve reproducibility.
      ERIC-PCR profiles and FT-IR spectra were obtained from strains belonging to the
      species Campylobacter coli and C. jejuni, normalized, and explored by
      hierarchical clustering and stepwise discriminant analysis. Strains could be
      differentiated by using mainly the first-derivative FT-IR spectral range, 1,200
      to 900 cm(-1) (described as the carbohydrate region). The reproducibility index
      varied depending on the ages of the cultures and on the spectral ranges
      investigated. Classification obtained by FT-IR spectroscopy provided valuable
      taxonomic information and was mostly in agreement with data from the genotypic
      method, ERIC-PCR. The classification functions obtained from the discriminant
      analysis allowed the identification of 98.72% of isolates from the validation
      set. FT-IR can serve as a valuable tool in the classification, identification,
      and typing of thermophilic Campylobacter isolates, and a number of types can be
      differentiated by means of FT-IR spectroscopy.

PMID- 16085821
TI  - Enhanced reactivity of Rhizopus oryzae lipase displayed on yeast cell surfaces in
      organic solvents: potential as a whole-cell biocatalyst in organic solvents.
AB  - Immobilization of enzymes on some solid supports has been used to stabilize
      enzymes in organic solvents. In this study, we evaluated applications of
      genetically immobilized Rhizopus oryzae lipase displayed on the cell surface of
      Saccharomyces cerevisiae in organic solvents and measured the catalytic activity
      of the displayed enzyme as a fusion protein with alpha-agglutinin. Compared to
      the activity of a commercial preparation of this lipase, the activity of the new
      preparation was 4.4 x 10(4)-fold higher in a hydrolysis reaction using p
      nitrophenyl palmitate and 3.8 x 10(4)-fold higher in an esterification reaction
      with palmitic acid and n-pentanol (0.2% H2O). Increased enzyme activity may occur
      because the lipase displayed on the yeast cell surface is stabilized by the cell
      wall. We used a combination of error-prone PCR and cell surface display to
      increase lipase activity. Of 7,000 colonies in a library of mutated lipases, 13
      formed a clear halo on plates containing 0.2% methyl palmitate. In organic
      solvents, the catalytic activity of 5/13 mutants was three- to sixfold higher
      than that of the original construct. Thus, yeast cells displaying the lipase can
      be used in organic solvents, and the lipase activity may be increased by a
      combination of protein engineering and display techniques. Thus, this immobilized
      lipase, which is more easily prepared and has higher activity than commercially
      available free and immobilized lipases, may be a practical alternative for the
      production of esters derived from fatty acids.

PMID- 16085822
TI  - Phosphate starvation-inducible gene ushA encodes a 5' nucleotidase required for
      growth of Corynebacterium glutamicum on media with nucleotides as the phosphorus
      source.
AB  - Phosphorus is an essential component of macromolecules, like DNA, and central
      metabolic intermediates, such as sugar phosphates, and bacteria possess enzymes
      and control mechanisms that provide an optimal supply of phosphorus from the
      environment. UDP-sugar hydrolases and 5' nucleotidases may play roles in signal
      transduction, as they do in mammals, in nucleotide salvage, as demonstrated for
      UshA of Escherichia coli, or in phosphorus metabolism. The Corynebacterium
      glutamicum gene ushA was found to encode a secreted enzyme which is active as a
      5' nucleotidase and a UDP-sugar hydrolase. This enzyme was synthesized and
      secreted into the medium when C. glutamicum was starved for inorganic phosphate.
      UshA was required for growth of C. glutamicum on AMP and UDP-glucose as sole
      sources of phosphorus. Thus, in contrast to UshA from E. coli, C. glutamicum UshA
      is an important component of the phosphate starvation response of this species
      and is necessary to access nucleotides and related compounds as sources of
      phosphorus.

PMID- 16085823
TI  - In vitro study of lipid biosynthesis in an anaerobically methane-oxidizing
      microbial mat.
AB  - The anaerobic oxidation of methane (AOM) is a key process in the global methane
      cycle, and the majority of methane formed in marine sediments is oxidized in this
      way. Here we present results of an in vitro 13CH4 labeling study (delta13CH4,
      approximately 5,400 per thousand) in which microorganisms that perform AOM in a
      microbial mat from the Black Sea were used. During 316 days of incubation, the
      13C uptake into the mat biomass increased steadily, and there were remarkable
      differences for individual bacterial and archaeal lipid compounds. The greatest
      shifts were observed for bacterial fatty acids (e.g., hexadec-11-enoic acid
      [16:1Delta11]; difference between the delta13C at the start and the end of the
      experiment [Deltadelta13C(start-end)], approximately 160 per thousand). In
      contrast, bacterial glycerol diethers exhibited only slight changes in delta13C
      (Deltadelta13C(start-end), approximately 10 per thousand). Differences were also
      found for individual archaeal lipids. Relatively high uptake of methane-derived
      carbon was observed for archaeol (Deltadelta13C(start-end), approximately 25 per
      thousand), a monounsaturated archaeol, and biphytanes, whereas for sn-2
      hydroxyarchaeol there was considerably less change in the delta13C
      (Deltadelta13C(start-end), approximately 2 per thousand). Moreover, an increase
      in the uptake of 13C for compounds with a higher number of double bonds within a
      suite of polyunsaturated 2,6,10,15,19-pentamethyleicosenes indicated that in
      methanotrophic archaea there is a biosynthetic pathway similar to that proposed
      for methanogenic archaea. The presence of group-specific biomarkers (for ANME-1
      and ANME-2 associations) and the observation that there were differences in 13C
      uptake into specific lipid compounds confirmed that multiple phylogenetically
      distinct microorganisms participate to various extents in biomass formation
      linked to AOM. However, the greater 13C uptake into the lipids of the sulfate
      reducing bacteria (SRB) than into the lipids of archaea supports the hypothesis
      that there is autotrophic growth of SRB on small methane-derived carbon compounds
      supplied by the methane oxidizers.

PMID- 16085824
TI  - First archaeal inorganic polyphosphate/ATP-dependent NAD kinase, from
      hyperthermophilic archaeon Pyrococcus horikoshii: cloning, expression, and
      characterization.
AB  - The gene (PH1074) encoding the NAD kinase of the hyperthermophilic archaeon
      Pyrococcus horikoshii was identified in the genome database, cloned, and
      functionally expressed in Escherichia coli. The recombinant enzyme was purified
      to homogeneity by heat treatment at 90 degrees C for 20 min and one successive
      HiTrap affinity chromatography step. The purified enzyme was easily precipitated
      by dialysis against phosphate buffer without NaCl and imidazole and was usually
      stored in buffer containing 0.5 M NaCl and 0.5 M imidazole to avoid
      precipitation. The molecular mass of the active enzyme was determined to be 145
      kDa by a gel filtration method, and the enzyme was composed of a tetramer of 37
      kDa subunits. The archaeal enzyme utilized several nucleoside triphosphates, such
      as GTP, CTP, UTP, and ITP, as well as ATP and inorganic polyphosphates [poly(P)]
      as phosphoryl donors for NAD phosphorylation. The enzyme utilized poly(P)27 (the
      average length of the phosphoryl chain was 27) as the most active inorganic
      polyphosphate for NAD phosphorylation. Thus, this enzyme is categorized as an
      inorganic polyphosphate/ATP-dependent NAD kinase. The enzyme was the most
      thermostable NAD kinase found to date: its activity was not lost by incubation at
      95 degrees C for 10 min. The enzyme showed classical Michaelis-Menten-type
      kinetics for NAD and ATP, but not for poly(P)27. The Km values for NAD were
      determined to be 0.30 and 0.40 mM when poly(P)27 and ATP, respectively, were used
      as the phosphoryl donors. The Km value for ATP was 0.29 mM, and the concentration
      of poly(P)27 which gave half of the maximum enzyme activity was 0.59 mM. The
      enzyme required several metal cations, such as Mg2+, Mn2+, or Ni2+, for its
      activity. The deduced amino acid sequence showed a low level of identity to those
      of E. coli ATP-dependent NAD kinase (31%) and the inorganic polyphosphate/ATP
      dependent NAD kinase of Mycobacterium tuberculosis (29%). This is the first
      description of the characteristics of a poly(P)/ATP-dependent NAD kinase from a
      hyperthermophilic archaeon.

PMID- 16085820
TI  - Phylogenetic characterization of a polychlorinated-dioxin- dechlorinating
      microbial community by use of microcosm studies.
AB  - Microcosms capable of reductive dechlorination of polychlorinated dibenzo-p
      dioxins/dibenzofurans (PCDD/Fs) were constructed in glass bottles by seeding them
      with a polluted river sediment and incubating them anaerobically with an organic
      medium. All of the PCDD/F congeners detected were equally reduced without the
      accumulation of significant amounts of less-chlorinated congeners as the
      intermediate or end products. Alternatively, large amounts of catechol and
      salicylic acid were produced in the upper aqueous phase. Thus, the dechlorination
      of PCDD/Fs and the oxidative degradation of the dechlorinated products seemed to
      take place simultaneously in the microcosm. Denaturing gel gradient
      electrophoresis and clone library analyses of PCR-amplified 16S rRNA genes from
      the microcosm showed that members of the phyla Firmicutes, Proteobacteria, and
      Bacteroidetes predominated. A significant number of Chloroflexi clones were also
      detected. Quantitative real-time PCR with specific primer sets showed that the
      16S rRNA genes of a putative dechlorinator, "Dehalococcoides," and its relatives
      accounted for 0.1% of the total rRNA gene copies of the microcosm. Most of the
      clones thus obtained formed a cluster distinct from the typical "Dehalococcoides"
      group. Quinone profiling indicated that ubiquinones accounted for 18 to 25% of
      the total quinone content, suggesting the coexistence and activity of ubiquinone
      containing aerobic bacteria. These results suggest that the apparent complete
      dechlorination of PCDD/Fs found in the microcosm was due to a combination of the
      dechlorinating activity of the "Dehalococcoides"-like organisms and the oxidative
      degradation of the dechlorinated products by aerobic bacteria with aromatic
      hydrocarbon dioxygenases.

PMID- 16085825
TI  - Secretion of human serum albumin by Kluyveromyces lactis overexpressing KlPDI1
      and KlERO1.
AB  - The control of protein conformation during translocation through the endoplasmic
      reticulum is often a bottleneck for heterologous protein production. The core
      pathway of the oxidative folding machinery includes two conserved proteins: Pdi1p
      and Ero1p. We increased the dosage of the genes encoding these proteins in the
      yeast Kluyveromyces lactis and evaluated the secretion of heterologous proteins.
      KlERO1, an orthologue of Saccharomyces cerevisiae ERO1, was cloned by functional
      complementation of the ts phenotype of an Scero1 mutant. The expression of KlERO1
      was induced by treatment of the cells with dithiothreitol and by overexpression
      of human serum albumin (HSA), a disulfide bond-rich protein. Duplication of
      either PDI1 or ERO1 led to a similar increase in HSA yield. Duplication of both
      genes accelerated the secretion of HSA and improved cell growth rate and yield.
      Increasing the dosage of KlERO1 did not affect the production of human
      interleukin 1beta, a protein that has no disulfide bridges. The results confirm
      that the ERO1 genes of S. cerevisiae and K. lactis are functionally similar even
      though portions of their coding sequence are quite different and the phenotypes
      of mutants overexpressing the genes differ. The marked effects of KlERO1 copy
      number on the expression of heterologous proteins with a high number of disulfide
      bridges suggests that control of KlERO1 and KlPDI1 is important for the
      production of high levels of heterologous proteins of this type.

PMID- 16085826
TI  - Responses of Baltic Sea ice and open-water natural bacterial communities to
      salinity change.
AB  - To investigate the responses of Baltic Sea wintertime bacterial communities to
      changing salinity (5 to 26 practical salinity units), an experimental study was
      conducted. Bacterial communities of Baltic seawater and sea ice from a coastal
      site in southwest Finland were used in two batch culture experiments run for 17
      or 18 days at 0 degrees C. Bacterial abundance, cell volume, and leucine and
      thymidine incorporation were measured during the experiments. The bacterial
      community structure was assessed using denaturing gradient gel electrophoresis
      (DGGE) of PCR-amplified partial 16S rRNA genes with sequencing of DGGE bands from
      initial communities and communities of day 10 or 13 of the experiment. The sea
      ice-derived bacterial community was metabolically more active than the open-water
      community at the start of the experiment. Ice-derived bacterial communities were
      able to adapt to salinity change with smaller effects on physiology and community
      structure, whereas in the open-water bacterial communities, the bacterial cell
      volume evolution, bacterial abundance, and community structure responses
      indicated the presence of salinity stress. The closest relatives for all eight
      partial 16S rRNA gene sequences obtained were either organisms found in polar sea
      ice and other cold habitats or those found in summertime Baltic seawater. All
      sequences except one were associated with the alpha- and gamma-proteobacteria or
      the Cytophaga-Flavobacterium-Bacteroides group. The overall physiological and
      community structure responses were parallel in ice-derived and open-water
      bacterial assemblages, which points to a linkage between community structure and
      physiology. These results support previous assumptions of the role of salinity
      fluctuation as a major selective factor shaping the sea ice bacterial community
      structure.

PMID- 16085827
TI  - Two rhizobial strains, Mesorhizobium loti MAFF303099 and Bradyrhizobium japonicum
      USDA110, encode haloalkane dehalogenases with novel structures and substrate
      specificities.
AB  - Haloalkane dehalogenases are key enzymes for the degradation of halogenated
      aliphatic pollutants. Two rhizobial strains, Mesorhizobium loti MAFF303099 and
      Bradyrhizobium japonicum USDA110, have open reading frames (ORFs), mlr5434 and
      blr1087, respectively, that encode putative haloalkane dehalogenase homologues.
      The crude extracts of Escherichia coli strains expressing mlr5434 and blr1087
      showed the ability to dehalogenate 18 halogenated compounds, indicating that
      these ORFs indeed encode haloalkane dehalogenases. Therefore, these ORFs were
      referred to as dmlA (dehalogenase from Mesorhizobium loti) and dbjA (dehalogenase
      from Bradyrhizobium japonicum), respectively. The principal component analysis of
      the substrate specificities of various haloalkane dehalogenases clearly showed
      that DbjA and DmlA constitute a novel substrate specificity class with
      extraordinarily high activity towards beta-methylated compounds. Comparison of
      the circular dichroism spectra of DbjA and other dehalogenases strongly suggested
      that DbjA contains more alpha-helices than the other dehalogenases. The
      dehalogenase activity of resting cells and Northern blot analyses both revealed
      that the dmlA and dbjA genes were expressed under normal culture conditions in
      MAFF303099 and USDA110 strain cells, respectively.

PMID- 16085828
TI  - Genetic characterization of accumulation of polyhydroxyalkanoate from styrene in
      Pseudomonas putida CA-3.
AB  - Pseudomonas putida CA-3 is capable of accumulating medium-chain-length
      polyhydroxyalkanoates (MCL-PHAs) when growing on the toxic pollutant styrene as
      the sole source of carbon and energy. In this study, we report on the molecular
      characterization of the metabolic pathways involved in this novel bioconversion.
      With a mini-Tn5 random mutagenesis approach, acetyl-coenzyme A (CoA) was
      identified as the end product of styrene metabolism in P. putida CA-3. Amplified
      flanking-region PCR was used to clone functionally expressed phenylacetyl-CoA
      catabolon genes upstream from the sty operon in P. putida CA-3, previously
      reported to generate acetyl-CoA moieties from the styrene catabolic intermediate,
      phenylacetyl-CoA. However, the essential involvement of a (non-phenylacetyl-CoA)
      catabolon-encoded 3-hydroxyacyl-CoA dehydrogenase is also reported. The link
      between de novo fatty acid synthesis and PHA monomer accumulation was
      investigated, and a functionally expressed 3-hydroxyacyl-acyl carrier protein-CoA
      transacylase (phaG) gene in P. putida CA-3 was identified. The deduced PhaG amino
      acid sequence shared >99% identity with a transacylase from P. putida KT2440,
      involved in 3-hydroxyacyl-CoA MCL-PHA monomer sequestration from de novo fatty
      acid synthesis under inorganic nutrient-limited conditions. Similarly, with P.
      putida CA-3, maximal phaG expression was observed only under nitrogen limitation,
      with concomitant PHA accumulation. Thus, beta-oxidation and fatty acid de novo
      synthesis appear to converge in the generation of MCL-PHA monomers from styrene
      in P. putida CA-3. Cloning and functional characterization of the pha locus,
      responsible for PHA polymerization/depolymerization is also reported and the
      significance and future prospects of this novel bioconversion are discussed.

PMID- 16085829
TI  - Correlation of phenotype with the genotype of egg-contaminating Salmonella
      enterica serovar Enteritidis.
AB  - The genotype of Salmonella enterica serovar Enteritidis was correlated with the
      phenotype using DNA-DNA microarray hybridization, ribotyping, and Phenotype
      MicroArray analysis to compare three strains that differed in colony morphology
      and phage type. No DNA hybridization differences were found between two phage
      type 13A (PT13A) strains that varied in biofilm formation; however, the ribotype
      patterns were different. Both PT13A strains had DNA sequences similar to that of
      bacteriophage Fels2, whereas the PT4 genome to which they were compared, as well
      as a PT4 field isolate, had a DNA sequence with some similarity to the
      bacteriophage ST64b sequence. Phenotype MicroArray analysis indicated that the
      two PT13A strains and the PT4 field isolate had similar respiratory activity
      profiles at 37 degrees C. However, the wild-type S. enterica serovar Enteritidis
      PT13A strain grew significantly better in 20% more of the 1,920 conditions tested
      when it was assayed at 25 degrees C than the biofilm-forming PT13A strain grew.
      Statistical analysis of the respiratory activity suggested that S. enterica
      serovar Enteritidis PT4 had a temperature-influenced dimorphic metabolism which
      at 25 degrees C somewhat resembled the profile of the biofilm-forming PT13A
      strain and that at 37 degrees C the metabolism was nearly identical to that of
      the wild-type PT13A strain. Although it is possible that lysogenic bacteriophage
      alter the balance of phage types on a farm either by lytic competition or by
      altering the metabolic processes of the host cell in subtle ways, the different
      physiologies of the S. enterica serovar Enteritidis strains correlated most
      closely with minor, rather than major, genomic changes. These results strongly
      suggest that the pandemic of egg-associated human salmonellosis that came into
      prominence in the 1980s is primarily an example of bacterial adaptive radiation
      that affects the safety of the food supply.

PMID- 16085830
TI  - Lactobacillus oligofermentans sp. nov., associated with spoilage of modified
      atmosphere-packaged poultry products.
AB  - Unidentified lactic acid bacterium (LAB) isolates which had mainly been detected
      in spoiled, marinated, modified atmosphere packaged (MAP) broiler meat products
      during two previous studies, were identified and analyzed for their phenotypic
      properties and the capability to produce biogenic amines. To establish the
      taxonomic position of these isolates, 16S rRNA gene sequence analysis, numerical
      analysis of ribopatterns, and DNA-DNA hybridization experiments were done.
      Unexpectedly for a meat-spoilage-associated LAB, the strains utilized glucose
      very weakly. According to the API 50 CHL test, arabinose and xylose were the only
      carbohydrates strongly fermented. None of the six strains tested for production
      of histamine, tyramine, tryptamine, phenylethylamine, putrescine, and cadaverine
      were able to produce these main meat-associated biogenic amines in vitro. The
      polyphasic taxonomy approach showed that these strains represent a new
      Lactobacillus species. The six isolates sequenced for the 16S rRNA encoding genes
      shared the highest similarity (95.0 to 96.3%) with the sequence of the
      Lactobacillus durianis type strain. In the phylogenetic tree, these isolates
      formed a distinct cluster within the Lactobacillus reuteri group, which also
      includes L. durianis. Numerical analyses of HindIII-EcoRI ribotypes placed all
      isolates together in a cluster with seven subclusters well separated from the L.
      reuteri group reference strains. The DNA-DNA hybridization levels between
      Lactobacillus sp. nov. isolates varied from 67 to 96%, and low hybridization
      levels (3 to 15%) were obtained with the L. durianis type strain confirming that
      these isolates belong to the same species different from L. durianis. The name
      Lactobacillus oligofermentans sp. nov. is proposed, with strain LMG 22743T (also
      known as DSM 15707T or AMKR18T) as the type strain.

PMID- 16085831
TI  - Expression of the psl operon in Pseudomonas aeruginosa PAO1 biofilms: PslA
      performs an essential function in biofilm formation.
AB  - The psl gene cluster, comprising 15 cotranscribed genes from Pseudomonas
      aeruginosa, was recently identified as being involved in exopolysaccharide
      biosynthesis and biofilm formation. In this study, we investigated the regulation
      of the psl gene cluster and the function of the first gene in this cluster, the
      pslA gene. PslA shows strong similarities to UDP-glucose lipid carriers. An
      isogenic marker-free pslA deletion mutant of P. aeruginosa PAO1 deficient in
      attachment and biofilm formation was used for complementation studies. The
      expression of only the pslA gene, comprising a coding region of 1,437 bp,
      restored the biofilm-forming phenotype of the wild type, indicating that PslA is
      required for biofilm formation by nonmucoid P. aeruginosa. The promoter region of
      the psl gene cluster, which encodes PslA-PslO, was identified by rapid
      amplification of cDNA 5' ends. Promoter assays using transcriptional fusions to
      lacZ and gfp indicated a constitutive expression of the psl cluster in planktonic
      cells and a highly regulated and localized expression in biofilms, respectively.
      Expression of the psl cluster in biofilms was almost exclusively found in the
      centers of microcolonies, as revealed by confocal laser scanning microscopy.
      These data suggest that constitutive expression of the psl operon enables
      efficient attachment to surfaces and that regulated localized psl operon
      expression is required for biofilm differentiation.

PMID- 16085832
TI  - Shewanella oneidensis MR-1 uses overlapping pathways for iron reduction at a
      distance and by direct contact under conditions relevant for Biofilms.
AB  - We developed a new method to measure iron reduction at a distance based on
      depositing Fe(III) (hydr)oxide within nanoporous glass beads. In this "Fe-bead"
      system, Shewanella oneidensis reduces at least 86.5% of the iron in the absence
      of direct contact. Biofilm formation accompanies Fe-bead reduction and is
      observable both macro- and microscopically. Fe-bead reduction is catalyzed by
      live cells adapted to anaerobic conditions, and maximal reduction rates require
      sustained protein synthesis. The amount of reactive ferric iron in the Fe-bead
      system is available in excess such that the rate of Fe-bead reduction is directly
      proportional to cell density; i.e., it is diffusion limited. Addition of either
      lysates prepared from anaerobic cells or exogenous electron shuttles stimulates
      Fe-bead reduction by S. oneidensis, but iron chelators or additional Fe(II) do
      not. Neither dissolved Fe(III) nor electron shuttling activity was detected in
      culture supernatants, implying that the mediator is retained within the biofilm
      matrix. Strains with mutations in omcB or mtrB show about 50% of the wild-type
      levels of reduction, while a cymA mutant shows less than 20% of the wild-type
      levels of reduction and a menF mutant shows insignificant reduction. The Fe-bead
      reduction defect of the menF mutant can be restored by addition of menaquinone,
      but menaquinone itself cannot stimulate Fe-bead reduction. Because the menF gene
      encodes the first committed step of menaquinone biosynthesis, no intermediates of
      the menaquinone biosynthetic pathway are used as diffusible mediators by this
      organism to promote iron reduction at a distance. CymA and menaquinone are
      required for both direct and indirect mineral reduction, whereas MtrB and OmcB
      contribute to but are not absolutely required for iron reduction at a distance.

PMID- 16085833
TI  - Expression of nitrite and nitric oxide reductases in free-living and plant
      associated Agrobacterium tumefaciens C58 cells.
AB  - A number of the bacteria that form associations with plants are denitrifiers. To
      learn more about how the association with plants affects expression of
      denitrification genes, the regulation of nitrite and nitric oxide reductases was
      investigated in Agrobacterium tumefaciens. Analysis of free-living cells revealed
      that expression of the genes encoding nitrite and nitric oxide reductases, nirK
      and nor, respectively, requires low-oxygen conditions, nitric oxide, and the
      transcriptional regulator NnrR. Expression of nor was monitored in plant
      associated bacteria using nor-gfp fusion expression. In root association
      experiments, only a small percentage of the attached cells were fluorescent, even
      when they were incubated under a nitrogen atmosphere. Inactivation of nirK had no
      significant effect on the ability of A. tumefaciens to bind to plant roots
      regardless of the oxygen tension, but it did decrease the occurrence of root
      associated fluorescent cells. When wild-type cells containing the gfp fusion were
      infiltrated into leaves, most cells eventually became fluorescent. The same
      result was obtained when a nirK mutant was used, suggesting that nitric oxide
      activated nor expression in the endophytic bacteria. Addition of a nitric oxide
      synthase inhibitor to block nitric oxide generation by the plant prevented gfp
      expression in infiltrated nitrite reductase mutants, demonstrating that plant
      derived nitric oxide can activate nor expression in infiltrated cells.

PMID- 16085834
TI  - Allophanate hydrolase, not urease, functions in bacterial cyanuric acid
      metabolism.
AB  - Growth substrates containing an s-triazine ring are typically metabolized by
      bacteria to liberate 3 mol of ammonia via the intermediate cyanuric acid. Over a
      25-year period, a number of original research papers and reviews have stated that
      cyanuric acid is metabolized in two steps to the 2-nitrogen intermediate urea. In
      the present study, allophanate, not urea, was shown to be the 2-nitrogen
      intermediate in cyanuric acid metabolism in all the bacteria examined. Six
      different experimental results supported this conclusion: (i) synthetic
      allophanate was shown to readily decarboxylate to form urea under acidic
      extraction and chromatography conditions used in previous studies; (ii) alkaline
      extraction methods were used to stabilize and detect allophanate in bacteria
      actively metabolizing cyanuric acid; (iii) the kinetic course of allophanate
      formation and disappearance was consistent with its being an intermediate in
      cyanuric acid metabolism, and no urea was observed in those experiments; (iv)
      protein extracts from cells grown on cyanuric acid contained allophanate
      hydrolase activity; (v) genes encoding the enzymes AtzE and AtzF, which produce
      and hydrolyze allophanate, respectively, were found in several cyanuric acid
      metabolizing bacteria; and (vi) TrzF, an AtzF homolog found in Enterobacter
      cloacae strain 99, was cloned, expressed in Escherichia coli, and shown to have
      allophanate hydrolase activity. In addition, we have observed that there are a
      large number of genes homologous to atzF and trzF distributed in phylogenetically
      distinct bacteria. In total, the data indicate that s-triazine metabolism in a
      broad class of bacteria proceeds through allophanate via allophanate hydrolase,
      rather than through urea using urease.

PMID- 16085835
TI  - Distribution of cryptosporidium genotypes in storm event water samples from three
      watersheds in New York.
AB  - To assess the source and public health significance of Cryptosporidium oocyst
      contamination in storm runoff, a PCR-restriction fragment length polymorphism
      technique based on the small-subunit rRNA gene was used in the analysis of 94
      storm water samples collected from the Malcolm Brook and N5 stream basins in New
      York over a 3-year period. The distribution of Cryptosporidium in this study was
      compared with the data obtained from 27 storm water samples from the Ashokan
      Brook in a previous study. These three watersheds represented different levels of
      human activity. Among the total of 121 samples analyzed from the three
      watersheds, 107 were PCR positive, 101 of which (94.4%) were linked to animal
      sources. In addition, C. hominis (W14) was detected in six samples collected from
      the Malcolm Brook over a 2-week period. Altogether, 22 Cryptosporidium species or
      genotypes were found in storm water samples from these three watersheds, only 11
      of which could be attributed to known species/groups of animals. Several
      Cryptosporidium spp. were commonly found in these three watersheds, including the
      W1 genotype from an unknown animal source, the W4 genotype from deer, and the W7
      genotype from muskrats. Some genotypes were found only in a particular watershed.
      Aliquots of 113 samples were also analyzed by the Environmental Protection Agency
      (EPA) Method 1623; 63 samples (55.7%) were positive for Cryptosporidium by
      microscopy, and 39 (78%) of the 50 microscopy-negative samples were positive by
      PCR. Results of this study demonstrate that molecular techniques can complement
      traditional detection methods by providing information on the source of
      contamination and the human-infective potential of Cryptosporidium oocysts found
      in water.

PMID- 16085836
TI  - Use of Saccharomyces cerevisiae BLYES expressing bacterial bioluminescence for
      rapid, sensitive detection of estrogenic compounds.
AB  - An estrogen-inducible bacterial lux-based bioluminescent reporter was developed
      in Saccharomyces cerevisiae for applications in chemical sensing and
      environmental assessment of estrogen disruptor activity. The strain, designated
      S. cerevisiae BLYES, was constructed by inserting tandem estrogen response
      elements between divergent yeast promoters GPD and ADH1 on pUTK401 (formerly
      pUA12B7) that constitutively express luxA and luxB to create pUTK407.
      Cotransformation of this plasmid with a second plasmid (pUTK404) containing the
      genes required for aldehyde synthesis (luxCDE) and FMN reduction (frp) yielded a
      bioluminescent bioreporter responsive to estrogen-disrupting compounds. For
      validation purposes, results with strain BLYES were compared to the colorimetric
      based estrogenic assay that uses the yeast lacZ reporter strain (YES). Strains
      BLYES and YES were exposed to 17beta-estradiol over the concentration range of
      1.2 x 10(-8) through 5.6 x 10(-12) M. Calculated 50% effective concentration
      values from the colorimetric and bioluminescence assays (n = 7) were similar at
      (4.4 +/- 1.1) x 10(-10) and (2.4 +/- 1.0) x 10(-10) M, respectively. The lower
      and upper limits of detection for each assay were also similar and were
      approximately 4.5 x 10(-11) to 2.8 x 10(-9) M. Bioluminescence was observed in as
      little as 1 h and reached its maximum in 6 h. In comparison, the YES assay
      required a minimum of 3 days for results. Strain BLYES fills the niche for rapid,
      high-throughput screening of estrogenic compounds and has the ability to be used
      for remote, near-real-time monitoring of estrogen-disrupting chemicals in the
      environment.

PMID- 16085837
TI  - Host species-specific metabolic fingerprint database for enterococci and
      Escherichia coli and its application to identify sources of fecal contamination
      in surface waters.
AB  - A metabolic fingerprint database of enterococci and Escherichia coli from 10 host
      groups of animals was developed to trace the sources of fecal contamination in
      surface waters. In all, 526 biochemical phenotypes (BPTs) of enterococci and 530
      E. coli BPTs were obtained from 4,057 enterococci and 3,728 E. coli isolates
      tested. Of these, 231 Enterococcus BPTs and 257 E. coli BPTs were found in
      multiple host groups. The remaining 295 Enterococcus BPTs and 273 E. coli BPTs
      were unique to individual host groups. The database was used to trace the sources
      of fecal contamination in a local creek. The mean diversities (Di) of enterococci
      (Di = 0.76 +/- 0.05) and E. coli (Di = 0.88 +/- 0.04) were high (maximum 1) in
      water samples, indicating diverse sources of fecal contamination. Overall, 71% of
      BPTs of enterococci and 67% of E. coli BPTs from water samples were identified as
      human and animal sources. Altogether, 248 Enterococcus BPTs and 282 E. coli BPTs
      were found in water samples. Among enterococci, 26 (10%) BPTs were identical to
      those of humans and 152 BPTs (61%) were identical to those of animals (animal
      BPTs). Among E. coli isolates, 36 (13%) BPTs were identical to those of humans
      and 151 (54%) BPTs were identical to those of animals. Of the animal BPTs, 101
      (66%) Enterococcus BPTs and 93 (62%) E. coli BPTs were also unique to individual
      animal groups. On the basis of these unique Enterococcus BPTs, chickens
      contributed 14% of contamination, followed by humans (10%), dogs (7%), and horses
      (6%). For E. coli, humans contributed 13% of contamination, followed by ducks
      (9%), cattle (7%), and chickens (6%). The developed metabolic fingerprint
      database was able to distinguish between human and animal sources as well as
      among animal species in the studied catchment.

PMID- 16085838
TI  - Identification and characterization of putative virulence genes and gene clusters
      in Aeromonas hydrophila PPD134/91.
AB  - Aeromonas hydrophila is a gram-negative opportunistic pathogen of animals and
      humans. The pathogenesis of A. hydrophila is multifactorial. Genomic subtraction
      and markers of genomic islands (GIs) were used to identify putative virulence
      genes in A. hydrophila PPD134/91. Two rounds of genomic subtraction led to the
      identification of 22 unique DNA fragments encoding 19 putative virulence factors
      and seven new open reading frames, which are commonly present in the eight
      virulence strains examined. In addition, four GIs were found, including O
      antigen, capsule, phage-associated, and type III secretion system (TTSS) gene
      clusters. These putative virulence genes and gene clusters were positioned on a
      physical map of A. hydrophila PPD134/91 to determine their genetic organization
      in this bacterium. Further in vivo study of insertion and deletion mutants showed
      that the TTSS may be one of the important virulence factors in A. hydrophila
      pathogenesis. Furthermore, deletions of multiple virulence factors such as S
      layer, serine protease, and metalloprotease also increased the 50% lethal dose to
      the same level as the TTSS mutation (about 1 log) in a blue gourami infection
      model. This observation sheds light on the multifactorial and concerted nature of
      pathogenicity in A. hydrophila. The large number of putative virulence genes
      identified in this study will form the basis for further investigation of this
      emerging pathogen and help to develop effective vaccines, diagnostics, and novel
      therapeutics.

PMID- 16085840
TI  - Isolation and characterization of a genetically tractable photoautotrophic Fe(II)
      oxidizing bacterium, Rhodopseudomonas palustris strain TIE-1.
AB  - We report the isolation and characterization of a phototrophic ferrous iron
      [Fe(II)]-oxidizing bacterium named TIE-1 that differs from other Fe(II)-oxidizing
      phototrophs in that it is genetically tractable. Under anaerobic conditions, TIE
      1 grows photoautotrophically with Fe(II), H2, or thiosulfate as the electron
      donor and photoheterotrophically with a variety of organic carbon sources. TIE-1
      also grows chemoheterotrophically in the dark. This isolate appears to be a new
      strain of the purple nonsulfur bacterial species Rhodopseudomonas palustris,
      based on physiological and phylogenetic analysis. Fe(II) oxidation is optimal at
      pH 6.5 to 6.9. The mineral products of Fe(II) oxidation are pH dependent: below
      pH 7.0 goethite (alpha-FeOOH) forms, and above pH 7.2 magnetite (Fe3O4) forms.
      TIE-1 forms colonies on agar plates and is sensitive to a variety of antibiotics.
      A hyperactive mariner transposon is capable of random insertion into the
      chromosome with a transposition frequency of approximately 10(-5). To identify
      components involved in phototrophic Fe(II) oxidation, mutants of TIE-1 were
      generated by transposon mutagenesis and screened for defects in Fe(II) oxidation
      in a cell suspension assay. Among approximately 12,000 mutants screened, 6 were
      identified that are specifically impaired in Fe(II) oxidation. Five of these
      mutants have independent disruptions in a gene that is predicted to encode an
      integral membrane protein that appears to be part of an ABC transport system; the
      sixth mutant has an insertion in a gene that is a homolog of CobS, an enzyme
      involved in cobalamin (vitamin B12) biosynthesis.

PMID- 16085841
TI  - Biodesulfurization of dibenzothiophene by microbial cells coated with magnetite
      nanoparticles.
AB  - Microbial cells of Pseudomonas delafieldii were coated with magnetic Fe3O4
      nanoparticles and then immobilized by external application of a magnetic field.
      Magnetic Fe3O4 nanoparticles were synthesized by a coprecipitation method
      followed by modification with ammonium oleate. The surface-modified Fe3O4
      nanoparticles were monodispersed in an aqueous solution and did not precipitate
      in over 18 months. Using transmission electron microscopy (TEM), the average size
      of the magnetic particles was found to be in the range from 10 to 15 nm. TEM
      cross section analysis of the cells showed further that the Fe3O4 nanoparticles
      were for the most part strongly absorbed by the surfaces of the cells and coated
      the cells. The coated cells had distinct superparamagnetic properties. The
      magnetization (delta(s)) was 8.39 emu.g(-1). The coated cells not only had the
      same desulfurizing activity as free cells but could also be reused more than five
      times. Compared to cells immobilized on Celite, the cells coated with Fe3O4
      nanoparticles had greater desulfurizing activity and operational stability.

PMID- 16085839
TI  - Characterization of botulinum progenitor toxins by mass spectrometry.
AB  - Botulinum toxin analysis has renewed importance. This study included the use of
      nanochromatography-nanoelectrospray-mass spectrometry/mass spectrometry to
      characterize the protein composition of botulinum progenitor toxins and to assign
      botulinum progenitor toxins to their proper serotype and strain by using
      currently available sequence information. Clostridium botulinum progenitor toxins
      from strains Hall, Okra, Stockholm, MDPH, Alaska, and Langeland and 89
      representing serotypes A through G, respectively, were reduced, alkylated,
      digested with trypsin, and identified by matching the processed product ion
      spectra of the tryptic peptides to proteins in accessible databases. All proteins
      known to be present in progenitor toxins from each serotype were identified.
      Additional proteins, including flagellins, ORF-X1, and neurotoxin binding
      protein, not previously reported to be associated with progenitor toxins, were
      present also in samples from several serotypes. Protein identification was used
      to assign toxins to a serotype and strain. Serotype assignments were accurate,
      and strain assignments were best when either sufficient nucleotide or amino acid
      sequence data were available. Minor difficulties were encountered using
      neurotoxin-associated protein identification for assigning serotype and strain.
      This study found that combined nanoscale chromatographic and mass spectrometric
      techniques can characterize C. botulinum progenitor toxin protein composition and
      that serotype/strain assignments based upon these proteins can provide accurate
      serotype and, in most instances, strain assignments using currently available
      information. Assignment accuracy will continue to improve as more
      nucleotide/amino acid sequence information becomes available for different
      botulinum strains.

PMID- 16085842
TI  - Chemobiosynthesis of novel 6-deoxyerythronolide B analogues by mutation of the
      loading module of 6-deoxyerythronolide B synthase 1.
AB  - Chemobiosynthesis (J. R. Jacobsen, C. R. Hutchinson, D. E. Cane, and C. Khosla,
      Science 277:367-369, 1997) is an important route for the production of polyketide
      analogues and has been used extensively for the production of analogues of 6
      deoxyerythronolide B (6-dEB). Here we describe a new route for chemobiosynthesis
      using a version of 6-deoxyerythronolide B synthase (DEBS) that lacks the loading
      module. When the engineered DEBS was expressed in both Escherichia coli and
      Streptomyces coelicolor and fed a variety of acyl-thioesters, several novel 15-R
      6-dEB analogues were produced. The simpler "monoketide" acyl-thioester substrates
      required for this route of 15-R-6-dEB chemobiosynthesis allow greater flexibility
      and provide a cost-effective alternative to diketide-thioester feeding to DEBS
      KS1(o) for the production of 15-R-6-dEB analogues. Moreover, the facile synthesis
      of the monoketide acyl-thioesters allowed investigation of alternative thioester
      carriers. Several alternatives to N-acetyl cysteamine were found to work
      efficiently, and one of these, methyl thioglycolate, was verified as a productive
      thioester carrier for mono- and diketide feeding in both E. coli and S.
      coelicolor.

PMID- 16085843
TI  - Concurrent quantitation of total campylobacter and total ciprofloxacin-resistant
      campylobacter loads in rinses from retail raw chicken carcasses from 2001 to 2003
      by direct plating at 42 degrees C.
AB  - This is the first report on the use of a normally lethal dose of ciprofloxacin in
      a Campylobacter agar medium to kill all ciprofloxacin-sensitive Campylobacter
      spp. but allow the selective isolation and quantitation of naturally occurring
      presumptive ciprofloxacin-resistant Campylobacter CFU in rinses from retail raw
      chicken carcasses (RTCC). Thermophilic-group total Campylobacter CFU and total
      ciprofloxacin-resistant Campylobacter CFU (irrespective of species) were
      concurrently quantified in rinses from RTCC by direct plating of centrifuged
      pellets from 10 or 50 ml out of 400-ml rinse subsamples concurrently on
      Campylobacter agar and ciprofloxacin-containing Campylobacter agar at 42 degrees
      C (detection limit = 0.90 log(10) CFU/carcass). For 2001, 2002, and 2003,
      countable Campylobacter CFU were recovered from 85%, 96%, and 57% of RTCC, while
      countable ciprofloxacin-resistant Campylobacter CFU were recovered from 60%, 59%,
      and 17.5% of RTCC, respectively. Total Campylobacter CFU loads in RTCC rinses
      ranged from 0.90 to 4.52, 0.90 to 4.58, and 0.90 to 4.48 log(10) CFU/carcass in
      2001, 2002, and 2003, respectively. Total ciprofloxacin-resistant Campylobacter
      CFU loads in RTCC rinses ranged from 0.90 to 4.06, 0.90 to 3.95, and 0.90 to 3.04
      log(10) CFU/carcass in 2001, 2002, and 2003, respectively. Overall, total
      Campylobacter loads of 0.90 to 2.0, 2 to 3, 3 to 4, 4 to 5 log(10) CFU/carcass,
      respectively, were recovered from 16%, 32%, 26%, and 5% of RTCC tested over the 2
      year sampling period. For the same period, total ciprofloxacin-resistant
      Campylobacter loads of 0.90 to 2.0, 2 to 3, 3 to 4, and 4 to 5 log(10)
      CFU/carcass, respectively, were recovered from 24%, 11%, 7%, and 0.2% of RTCC
      tested. There was a steady decline in total Campylobacter and total ciprofloxacin
      resistant Campylobacter loads in RTCC rinses from 2001/2002 to 2003.

PMID- 16085844
TI  - Isolation and characterization of a novel single-stranded RNA Virus infectious to
      a marine fungoid protist, Schizochytrium sp. (Thraustochytriaceae,
      Labyrinthulea).
AB  - Thraustochytrids are cosmopolitan osmoheterotrophic microorganisms that play
      important roles as decomposers, producers of polyunsaturated fatty acids, and
      pathogens of mollusks, especially in coastal ecosystems. SssRNAV, a novel single
      stranded RNA (ssRNA) virus infecting the marine fungoid protist Schizochytrium
      sp. (Labyrinthulea, Thraustochytriaceae) was isolated from the coastal water of
      Kobe Harbor, Japan, in July 2000, and its basic characteristics were examined.
      The virus particle is icosahedral, lacks a tail, and is ca. 25 nm in diameter.
      SssRNAV formed crystalline arrays and random assemblies within the cytoplasm of
      host cells, and it was also concentrated along the intracellular membrane
      structures. By means of one-step growth experiments, the lytic cycle and the
      burst size were estimated to be <8 h and 5.8 x 10(3) to 6.4 x 10(4) infectious
      units per host cell, respectively. SssRNAV had a single molecule of ssRNA that
      was approximately 10.2 kb long, three major proteins (37, 34, and 32 kDa), and
      two minor proteins (80 and 18 kDa). Although SssRNAV was considered to have some
      similarities with invertebrate viruses belonging to the family Dicistroviridae
      based on its partial nucleotide sequence, further genomic analysis is required to
      determine the detailed classification and nomenclature of SssRNAV. Our results
      indicate that viral infection is one of the significant factors controlling the
      dynamics of thraustochytrids and provide new insights into understanding the
      ecology of these organisms.

PMID- 16085845
TI  - Rapid detection of enteroviruses in small volumes of natural waters by real-time
      quantitative reverse transcriptase PCR.
AB  - Despite viral contamination of recreational waters, only bacterial, not viral,
      indicators are monitored routinely, due to a lack of rapid and cost-effective
      assays. We used negatively charged filters to capture enteroviruses from seawater
      and freshwater. Viral RNA was extracted using a commercial kit, and the viruses
      were quantified by real-time quantitative reverse transcriptase PCR (qRT-PCR).
      Poliovirus (6.6 to 330,000 virus particles/ml) was added to samples from
      watersheds in Los Angeles, California, and analysis showed that with 50-ml
      samples, a cellulose acetate/nitrate (HA) filter yielded final recovery of 51%
      (r2= 0.99) in fresh water and 23% (r2= 0.90) in seawater. However, for additions
      of low levels of virus (more likely to represent field samples; <10(4)
      enterovirus particles/ml), the recovery was lower and more variable, with HA
      being best in freshwater (17%, r2= 0.97) and the type GF/F glass filter having
      higher average recovery in seawater (GF/F, 17%; r2= 0.93; HA 12%, r2= 0.87). The
      optimized method was used with 1-liter field samples from two very different
      freshwater "creeks" that drain into Santa Monica Bay, California: Topanga Creek
      (TC), a relatively pristine mountain creek, and Ballona Creek (BC), a concrete
      lined urban storm drain. One TC site out of 10 and 2 BC sites out of 7 tested
      significantly positive for enteroviruses, with higher enterovirus concentrations
      in BC than in TC (ca. 10 to 25 versus 1 equivalent enterovirus particle/ml). The
      presented filtration-qRT-PCR approach is fast (<8 h from sampling to results),
      sensitive, and cost efficient and is promising for monitoring viral contamination
      in environmental water samples.

PMID- 16085846
TI  - Activation of the protein kinase C1 pathway upon continuous heat stress in
      Saccharomyces cerevisiae is triggered by an intracellular increase in osmolarity
      due to trehalose accumulation.
AB  - This paper reports on physiological and molecular responses of Saccharomyces
      cerevisiae to heat stress conditions. We observed that within a very narrow range
      of culture temperatures, a shift from exponential growth to growth arrest and
      ultimately to cell death occurred. A detailed analysis was carried out of the
      accumulation of trehalose and the activation of the protein kinase C1 (PKC1)
      (cell integrity) pathway in both glucose- and ethanol-grown cells upon
      temperature upshifts within this narrow range of growth temperatures. It was
      observed that the PKC1 pathway was hardly activated in a tps1 mutant that is
      unable to accumulate any trehalose. Furthermore, it was observed that an increase
      of the extracellular osmolarity during a continuous heat stress prevented the
      activation of the pathway. The results of these analyses support our hypothesis
      that under heat stress conditions the activation of the PKC1 pathway is triggered
      by an increase in intracellular osmolarity, due to the accumulation of trehalose,
      rather than by the increase in temperature as such.

PMID- 16085847
TI  - Low intraspecific diversity in a polynucleobacter subcluster population
      numerically dominating bacterioplankton of a freshwater pond.
AB  - Cultivation-dependent and -independent methods were combined to investigate the
      microdiversity of a Polynucleobacter subcluster population (Betaproteobacteria)
      numerically dominating the bacterioplankton of a small, humic freshwater pond.
      Complete coverage of the population by cultivation allowed the analysis of
      microdiversity beyond the phylogenetic resolution of ribosomal markers.
      Fluorescent in situ hybridization with two probes specific for the narrow
      subcluster C (PnecC bacteria) of the Polynucleobacter cluster revealed that this
      population contributed up to 60% to the total number of bacterioplankton cells.
      Microdiversity was investigated for a date at which the highest relative numbers
      of PnecC were observed. A clone library of fragments of the ribosomal operon (16S
      rRNA genes, complete 16S-23S internal transcribed spacer 1 [ITS1], partial 23S
      rRNA genes) amplified with universal bacterial primers was constructed. The
      library was stepwise screened for fragments from PnecC bacteria and for different
      ITS genotypes of PnecC bacteria. The isolated PnecC strains were characterized by
      sequencing of the 16S rRNA genes and the ITS1. Both the clone library and the
      established culture collection contained only the same three ITS genotypes, and
      one of them contributed 46% to the entire number of clones. Genomic
      fingerprinting of the isolates with several methods always resulted in the
      detection of only one fingerprint per ITS genotype. We conclude that a
      Polynucleobacter population with an extremely low intraspecific diversity and an
      uneven structure numerically dominated the bacterioplankton community in the
      investigated habitat. This low intraspecific diversity is in strong contrast to
      the high intraspecific diversities found in marine bacterial populations.

PMID- 16085848
TI  - Characterization of carbohydrate-binding cytochrome b562 from the white-rot
      fungus Phanerochaete chrysosporium.
AB  - cDNA encoding a hemoprotein similar to the cytochrome domain of extracellular
      flavocytochrome cellobiose dehydrogenase (CDH) was cloned from the white-rot
      fungus Phanerochaete chrysosporium. The deduced amino acid sequence implies that
      there is a two-domain structure consisting of an N-terminal cytochrome domain and
      a C-terminal family 1 carbohydrate-binding module (CBM1) but that the flavin
      containing domain of CDH is not present. The gene transcripts were observed in
      cultures in cellulose medium but not in cultures in glucose medium, suggesting
      that there is regulation by carbon catabolite repression. The gene was
      successfully overexpressed in Pichia pastoris, and the recombinant protein was
      designated carbohydrate-binding cytochrome b562 (CBCyt. b562). The resonance
      Raman spectrum suggested that the heme of CBCyt. b562 is 6-coordinated in both
      the ferric and ferrous states. Moreover, the redox potential measured by cyclic
      voltammetry was similar to that of the cytochrome domain of CDH. These results
      suggest that the redox characteristics may be similar to those of the cytochrome
      domain of CDH, and so CBCyt. b562 may have an electron transfer function. In a
      binding study with various carbohydrates, CBCyt. b562 was adsorbed with high
      affinity on both cellulose and chitin. As far as we know, this is the first
      example of a CBM1 connected to a domain without apparent catalytic activity for
      carbohydrate; this CBM1 may play a role in localization of the redox protein on
      the surface of cellulose or on the fungal sheath in vivo.

PMID- 16085849
TI  - Structure and topology of microbial communities in the major gut compartments of
      Melolontha melolontha larvae (Coleoptera: Scarabaeidae).
AB  - Physicochemical gut conditions and the composition and topology of the intestinal
      microbiota in the major gut compartments of the root-feeding larva of the
      European cockchafer (Melolontha melolontha) were studied. Axial and radial
      profiles of pH, O2, H2, and redox potential were measured with microsensors.
      Terminal restriction fragment length polymorphism (T-RFLP) analysis of bacterial
      16S rRNA genes in midgut samples of individual larvae revealed a simple but
      variable and probably nonspecific community structure. In contrast, the T-RFLP
      profiles of the hindgut samples were more diverse but highly similar, especially
      in the wall fraction, indicating the presence of a gut-specific community
      involved in digestion. While high acetate concentrations in the midgut and
      hindgut (34 and 15 mM) corroborated the presence of microbial fermentation in
      both compartments, methanogenesis was confined to the hindgut. Methanobrevibacter
      spp. were the only methanogens detected and were restricted to this compartment.
      Bacterial 16S rRNA gene clone libraries of the hindgut were dominated by clones
      related to the Clostridiales. Clones related to the Actinobacteria, Bacillales,
      Lactobacillales, and gamma-Proteobacteria were restricted to the lumen, whereas
      clones related to the beta- and delta-Proteobacteria were found only on the
      hindgut wall. Results of PCR-based analyses and fluorescence in situ
      hybridization of whole cells with group-specific oligonucleotide probes
      documented that Desulfovibrio-related bacteria comprise 10 to 15% of the
      bacterial community at the hindgut wall. The restriction of the sulfate-reducer
      specific adenosine-5'-phosphosulfate reductase gene apsA to DNA extracts of the
      hindgut wall in larvae from four other populations in Europe suggested that
      sulfate reducers generally colonize this habitat.

PMID- 16085850
TI  - Analysis of the hupSL operon of the nonheterocystous cyanobacterium Lyngbya
      majuscula CCAP 1446/4: regulation of transcription and expression under a light
      dark regimen.
AB  - This work presents the characterization of an uptake hydrogenase from a marine
      filamentous nonheterocystous cyanobacterium, Lyngbya majuscula CCAP 1446/4. The
      structural genes encoding the uptake hydrogenase (hupSL) were isolated and
      characterized, and regulatory sequences were identified upstream of hupS. In
      silico analysis highlighted various sets of long repetitive sequences within the
      hupSL intergenic region and downstream of hupL. The transcriptional regulator
      that operates global nitrogen control in cyanobacteria (NtcA) was shown to bind
      to the promoter region, indicating its involvement in the transcriptional
      regulation of hupSL. Under N2-fixing conditions and a 12-h light/12-h dark
      regime, H2 uptake activity was shown to follow a daily pattern with a clear
      maximum towards the end of the dark period, preceded by an increase in the
      transcript levels initiated in the end of the light phase. Novel antibodies
      directed against HupL of Lyngbya majuscula CCAP 1446/4 were used to monitor the
      protein levels throughout the 24-h period. The results suggest that protein
      turnover occurs, with degradation taking place during the light phase and de novo
      synthesis occurring during the dark phase, coinciding with the pattern of H2
      uptake. Taking into account our results and the established correlation between
      the uptake hydrogenase activity and N2 fixation in cyanobacteria, it seems
      probable that both processes are confined to the dark period in aerobically grown
      cells of Lyngbya majuscula CCAP 1446/4.

PMID- 16085851
TI  - Mycosubtilin overproduction by Bacillus subtilis BBG100 enhances the organism's
      antagonistic and biocontrol activities.
AB  - A Bacillus subtilis derivative was obtained from strain ATCC 6633 by replacement
      of the native promoter of the mycosubtilin operon by a constitutive promoter
      originating from the replication gene repU of the Staphylococcus aureus plasmid
      pUB110. The recombinant strain, designated BBG100, produced up to 15-fold more
      mycosubtilin than the wild type produced. The overproducing phenotype was related
      to enhancement of the antagonistic activities against several yeasts and
      pathogenic fungi. Hemolytic activities were also clearly increased in the
      modified strain. Mass spectrometry analyses of enriched mycosubtilin extracts
      showed similar patterns of lipopeptides for BBG100 and the wild type.
      Interestingly, these analyses also revealed a new form of mycosubtilin which was
      more easily detected in the BBG100 sample. When tested for its biocontrol
      potential, wild-type strain ATCC 6633 was almost ineffective for reducing a
      Pythium infection of tomato seedlings. However, treatment of seeds with the
      BBG100 overproducing strain resulted in a marked increase in the germination rate
      of seeds. This protective effect afforded by mycosubtilin overproduction was also
      visualized by the significantly greater fresh weight of emerging seedlings
      treated with BBG100 compared to controls or seedlings inoculated with the wild
      type strain.

PMID- 16085852
TI  - Involvement of a branched-chain aminotransferase in production of volatile sulfur
      compounds in Yarrowia lipolytica.
AB  - The enzymatic degradation of L-methionine and the subsequent formation of
      volatile sulfur compounds (VSCs) are essential for the development of the typical
      flavor in cheese. In the yeast Yarrowia lipolytica, the degradation of L
      methionine was accompanied by the formation of the transamination product 4
      methylthio-2-oxobutyric acid. A branched-chain aminotransferase gene (YlBCA1) of
      Y. lipolytica was amplified, and the L-methionine-degrading activity and the
      aminotransferase activity were measured in a genetically modified strain and
      compared to those of the parental strain. Our work shows that L-methionine
      degradation via transamination is involved in formation of VSCs in Y. lipolytica.

PMID- 16085853
TI  - Methanogen diversity evidenced by molecular characterization of methyl coenzyme M
      reductase A (mcrA) genes in hydrothermal sediments of the Guaymas Basin.
AB  - The methanogenic community in hydrothermally active sediments of Guaymas Basin
      (Gulf of California, Mexico) was analyzed by PCR amplification, cloning, and
      sequencing of methyl coenzyme M reductase (mcrA) and 16S rRNA genes. Members of
      the Methanomicrobiales and Methanosarcinales dominated the mcrA and 16S rRNA
      clone libraries from the upper 15 cm of the sediments. Within the H2/CO2- and
      formate-utilizing family Methanomicrobiales, two mcrA and 16S rRNA lineages were
      closely affiliated with cultured species of the genera Methanoculleus and
      Methanocorpusculum. The most frequently recovered mcrA PCR amplicons within the
      Methanomicrobiales did not branch with any cultured genera. Within the
      nutritionally versatile family Methanosarcinales, one 16S rRNA amplicon and most
      of the mcrA PCR amplicons were affiliated with the obligately acetate utilizing
      species Methanosaeta concilii. The mcrA clone libraries also included phylotypes
      related to the methyl-disproportionating genus Methanococcoides. However, two
      mcrA and two 16S rRNA lineages within the Methanosarcinales were unrelated to any
      cultured genus. Overall, the clone libraries indicate a diversified methanogen
      community that uses H2/CO2, formate, acetate, and methylated substrates.
      Phylogenetic affiliations of mcrA and 16S rRNA clones with thermophilic and
      nonthermophilic cultured isolates indicate a mixed mesophilic and thermophilic
      methanogen community in the surficial Guaymas sediments.

PMID- 16085854
TI  - Characterization of an inducible phenylserine aldolase from Pseudomonas putida 24
      1.
AB  - An inducible phenylserine aldolase (L-threo-3-phenylserine benzaldehyde-lyase, EC
      4.1.2.26), which catalyzes the cleavage of L-3-phenylserine to yield benzaldehyde
      and glycine, was purified to homogeneity from a crude extract of Pseudomonas
      putida 24-1 isolated from soil. The enzyme was a hexamer with the apparent
      subunit molecular mass of 38 kDa and contained 0.7 mol of pyridoxal 5' phosphate
      per mol of the subunit. The enzyme exhibited absorption maxima at 280 and 420 nm.
      The maximal activity was obtained at about pH 8.5. The enzyme acted on L-threo-3
      phenylserine (Km, 1.3 mM), l-erythro-3-phenylserine (Km, 4.6 mM), l-threonine
      (Km, 29 mM), and L-allo-threonine (Km, 22 mM). In the reverse reaction, threo-
      and erythro- forms of L-3-phenylserine were produced from benzaldehyde and
      glycine. The optimum pH for the reverse reaction was 7.5. The structural gene
      coding for the phenylserine aldolase from Pseudomonas putida 24-1 was cloned and
      overexpressed in Escherichia coli cells. The nucleotide sequence of the
      phenylserine aldolase gene encoded a peptide containing 357 amino acids with a
      calculated molecular mass of 37.4 kDa. The recombinant enzyme was purified and
      characterized. Site-directed mutagenesis experiments showed that replacement of
      K213 with Q resulted in a loss of the enzyme activity, with a disappearance of
      the absorption maximum at 420 nm. Thus, K213 of the enzyme probably functions as
      an essential catalytic residue, forming a Schiff base with pyridoxal 5'
      phosphate.

PMID- 16085855
TI  - Cadmium accumulation and DNA homology with metal resistance genes in sulfate
      reducing bacteria.
AB  - Cadmium resistance (0.1 to 1.0 mM) was studied in four pure and one mixed culture
      of sulfate-reducing bacteria (SRB). The growth of the bacteria was monitored with
      respect to carbon source (lactate) oxidation and sulfate reduction in the
      presence of various concentrations of cadmium chloride. Two strains Desulfovibrio
      desulfuricans DSM 1926 and Desulfococcus multivorans DSM 2059 showed the highest
      resistance to cadmium (0.5 mM). Transmission electron microscopy of the two
      strains showed intracellular and periplasmic accumulation of cadmium. Dot blot
      DNA hybridization using the probes for the smtAB, cadAC, and cadD genes indicated
      the presence of similar genetic determinants of heavy metal resistance in the SRB
      tested. DNA sequencing of the amplified DNA showed strong nucleotide homology in
      all the SRB strains with the known smtAB genes encoding synechococcal
      metallothioneins. Protein homology with the known heavy metal-translocating
      ATPases was also detected in the cloned amplified DNA of Desulfomicrobium
      norvegicum I1 and Desulfovibrio desulfuricans DSM 1926, suggesting the presence
      of multiple genetic mechanisms of metal resistance in the two strains.

PMID- 16085856
TI  - 16S rRNA sequences and differences in bacteria isolated from the Muztag Ata
      glacier at increasing depths.
AB  - Small subunit 16S rRNA sequences, growth temperatures, and phylogenetic
      relationships have been established for 129 bacterial isolates recovered under
      aerobic growth conditions from different regions of a 22-m ice core from the
      Muztag Ata Mountain glacier on the Pamirs Plateau (China). Only 11% were
      psychrophiles (grew at 2 degrees C or -2 degrees C up to approximately 20 degrees
      C), although the majority (82%) were psychrotolerant (grew at 2 degrees C or -2
      degrees C up to 37 degrees C). The majority of the isolates had 16S rRNA
      sequences similar to previously determined sequences, ranging from 85% to 100%
      identical to database sequences. Based on their 16S rRNA sequences, 42.6% of the
      isolates were high-G+C (HGC) gram-positive bacteria, 23.3% were gamma
      Proteobacteria, 14.7% were alpha-Proteobacteria, 14.7% were Flavobacteria, and
      4.7% were low-G+C (LGC) gram-positive bacteria. There were clear differences in
      the depth distribution, with Proteobacteria, HGC/Cytophaga-Flavobacterium
      Bacteroides (CFB), Proteobacteria, LGC/CFB/HGC, Cryobacterium psychrophilum,
      HGC/CFB, Proteobacteria/HGC/CFB, and HGC/CFB being the predominant isolates from
      ice that originated from 2.7 to 3.8, 6.2, 7.5, 8.3, 9.0, 9.7, 12.5, and 15.3 m
      below the surface, respectively. This layered distribution of bacterial isolates
      presumably reflects both differences in bacteria inhabiting the glacier's
      surface, differences in bacteria deposited serendipitously on the glacier's
      surface by wind and snowfall, and nutrient availability within the ice.

PMID- 16085857
TI  - Mobility of protozoa through narrow channels.
AB  - Microbes in the environment are profoundly affected by chemical and physical
      heterogeneities occurring on a spatial scale of millimeters to micrometers.
      Physical refuges are critical for maintaining stable bacterial populations in the
      presence of high predation pressure by protozoa. The effects of microscale
      heterogeneity, however, are difficult to replicate and observe using conventional
      experimental techniques. The objective of this research was to investigate the
      effect of spatial constraints on the mobility of six species of marine protozoa.
      Microfluidic devices were created with small channels similar in size to pore
      spaces in soil or sediment systems. Individuals from each species of protozoa
      tested were able to rapidly discover and move within these channels. The time
      required for locating the channel entrance from the source well increased with
      protozoan size and decreased with channel height. Protozoa of every species were
      able to pass constrictions with dimensions equal to or smaller than the
      individual's unconstrained cross-sectional area. Channel geometry was also an
      important factor affecting protozoan mobility. Linear rates of motion for various
      species of protozoa varied by channel size. In relatively wide channels, typical
      rates of motion were 300 to 500 microm s(-1) (or about 1 m per hour). As the
      channel dimensions decreased, however, motilities slowed more than an order of
      magnitude to 20 microm s(-1). Protozoa were consistently observed to exhibit
      several strategies for successfully traversing channel reductions. The empirical
      results and qualitative observations resulting from this research help define the
      physical limitations on protozoan grazing, a critical process affecting microbes
      in the environment.

PMID- 16085858
TI  - Diurnal variation of cell proliferation in three bacterial taxa from coastal
      North Sea waters.
AB  - Pulse-labeling with bromodeoxyuridine (BrdU) in combination with fluorescence in
      situ hybridization was applied to quantify the percentage of proliferating cells
      in coastal North Sea waters. In order to assess diurnal variability, we sampled
      eight or nine times, respectively, within 3 consecutive days at two seasons.
      Bacteria affiliated with the Roseobacter, SAR86, and NOR5 lineages constituted on
      average 19% +/- 3%, 8% +/- 2%, and 6% +/- 1% of all cells in May 2002 and 17% +/-
      3%, 10% +/- 2%, and 11% +/- 3% in August. The relative abundances of the three
      populations either remained stable, or they changed very gradually during the
      observation periods. On average, 38 and 39% of all Bacteria exhibited DNA de novo
      synthesis in May and August, respectively. The fractions of proliferating cells
      in bacteria of the SAR86 (May, 59%; August, 72%) and the Roseobacter (48 and 53%)
      lineages were significantly above the community average. A substantial cell
      proliferation of population NOR5 (34%) was only encountered in August,
      concomitant with a dinoflagellate bloom. Significant short-term fluctuations of
      DNA-synthesizing cells were observed in Roseobacter during May and in NOR5 during
      August, hinting at a pronounced (temporal or spatial) mesoscale patchiness of
      growth rates in these populations. Since the BrdU proliferation assay is
      susceptible to misinterpretation, we also modeled the expected number of labeled
      cells at increasing BrdU incubation times in a slowly growing bacterial
      population. We suggest that the absence of visible DNA synthesis in marine
      bacterioplankton cells after DNA pulse-labeling must not be interpreted as an
      indication of cell "inactivity."

PMID- 16085859
TI  - Critical factors influencing the occurrence of Vibrio cholerae in the environment
      of Bangladesh.
AB  - The occurrence of outbreaks of cholera in Africa in 1970 and in Latin America in
      1991, mainly in coastal communities, and the appearance of the new serotype
      Vibrio cholerae O139 in India and subsequently in Bangladesh have stimulated
      efforts to understand environmental factors influencing the growth and geographic
      distribution of epidemic Vibrio cholerae serotypes. Because of the severity of
      recent epidemics, cholera is now being considered by some infectious disease
      investigators as a "reemerging" disease, prompting new work on the ecology of
      vibrios. Epidemiological and ecological surveillance for cholera has been under
      way in four rural, geographically separated locations in Bangladesh for the past
      4 years, during which both clinical and environmental samples were collected at
      biweekly intervals. The clinical epidemiology portion of the research has been
      published (Sack et al., J. Infect. Dis. 187:96-101, 2003). The results of
      environmental sampling and analysis of the environmental and clinical data have
      revealed significant correlations of water temperature, water depth, rainfall,
      conductivity, and copepod counts with the occurrence of cholera toxin-producing
      bacteria (presumably V. cholerae). The lag periods between increases or decreases
      in units of factors, such as temperature and salinity, and occurrence of cholera
      correlate with biological parameters, e.g., plankton population blooms. The new
      information on the ecology of V. cholerae is proving useful in developing
      environmental models for the prediction of cholera epidemics.

PMID- 16085860
TI  - Elevated temperature enhances virulence of Erwinia carotovora subsp. carotovora
      strain EC153 to plants and stimulates production of the quorum sensing signal, N
      acyl homoserine lactone, and extracellular proteins.
AB  - Erwinia carotovora subsp. atroseptica, E. carotovora subsp. betavasculorum, and
      E. carotovora subsp. carotovora produce high levels of extracellular enzymes,
      such as pectate lyase (Pel), polygalacturonase (Peh), cellulase (Cel), and
      protease (Prt), and the quorum-sensing signal N-acyl-homoserine lactone (AHL) at
      28 degrees C. However, the production of these enzymes and AHL by these bacteria
      is severely inhibited during growth at elevated temperatures (31.2 degrees C for
      E. carotovora subsp. atroseptica and 34.5 degrees C for E. carotovora subsp.
      betavasculorum and most E. carotovora subsp. carotovora strains). At elevated
      temperatures these bacteria produce high levels of RsmA, an RNA binding protein
      that promotes RNA decay. E. carotovora subsp. carotovora strain EC153 is an
      exception in that it produces higher levels of Pel, Peh, Cel, and Prt at 34.5
      degrees C than at 28 degrees C. EC153 also causes extensive maceration of celery
      petioles and Chinese cabbage leaves at 34.5 degrees C, which correlates with a
      higher growth rate and higher levels of rRNA and AHL. The lack of pectinase
      production by E. carotovora subsp. carotovora strain Ecc71 at 34.5 degrees C
      limits the growth of this organism in plant tissues and consequently impairs its
      ability to cause tissue maceration. Comparative studies with ahlI (the gene
      encoding a putative AHL synthase), pel-1, and peh-1 transcripts documented that
      at 34.5 degrees C the RNAs are more stable in EC153 than in Ecc71. Our data
      reveal that overall metabolic activity, AHL levels, and mRNA stability are
      responsible for the higher levels of extracellular protein production and the
      enhanced virulence of EC153 at 34.5 degrees C compared to 28 degrees C.

PMID- 16085861
TI  - Molecular characterization of Korean Bacillus anthracis isolates by amplified
      fragment length polymorphism analysis and multilocus variable-number tandem
      repeat analysis.
AB  - We analyzed the genetic relationships and molecular characteristics of 34
      Bacillus anthracis isolates from soil and clinical samples in various regions of
      Korea and 17 related Bacillus species, using the amplified fragment length
      polymorphism (AFLP) and multilocus variable-number tandem repeat (MLVA)
      approaches. Triplicate AFLP profiles of these strains showed high reproducibility
      and identified 376 polymorphisms. AFLP phylogenetic analysis of B. anthracis
      isolates showed a high level of similarity, 0.93, and this monomorphic fragment
      profile proved to be useful to differentiate B. anthracis strains from other
      Bacillus species. The B. cereus group was separated from other Bacillus species
      at a level of similarity of 0.68. Among them, some B. cereus strains showed
      genetic interspersion with B. thuringiensis strains. The evolutionary pattern of
      nucleotide differences among B. anthracis strains with the eight MLVA markers
      showed nine MLVA types. Three MLVA types, M1 to M3, were pathogenic B. anthracis
      isolates and were assigned as new genotypes belonging to the A4 and B3 clusters,
      compared with 89 genotypes deduced from previous data. This indicates that
      differences in cluster prevalence and distribution may be influenced more by MLVA
      markers on two plasmids loci and human activity. Consequently, we suggest that
      the novel MLVA type may represent significant evidence for historic adaptation to
      environmental conditions of the Asian continent, particularly Korea. Therefore,
      MLVA techniques may be available for molecular monitoring on anthrax-release
      related bioterrorism and further study is required for the continuous
      epidemiological study of variable anthrax collections.

PMID- 16085862
TI  - Expression of 17 genes in Clostridium thermocellum ATCC 27405 during fermentation
      of cellulose or cellobiose in continuous culture.
AB  - Clostridium thermocellum is a thermophilic, anaerobic, cellulolytic bacterium
      that produces ethanol and acetic acid as major fermentation end products. The
      effect of growth conditions on gene expression in C. thermocellum ATCC 27405 was
      studied using cells grown in continuous culture under cellobiose or cellulose
      limitation over a approximately 10-fold range of dilution rates (0.013 to 0.16 h(
      1)). Fermentation product distribution displayed similar patterns in cellobiose-
      or cellulose-grown cultures, including substantial shifts in the proportion of
      ethanol and acetic acid with changes in growth rate. Expression of 17 genes
      involved or potentially involved in cellulose degradation, intracellular
      phosphorylation, catabolite repression, and fermentation end product formation
      was quantified by real-time PCR, with normalization to two calibrator genes (recA
      and the 16S rRNA gene) to determine relative expression. Thirteen genes displayed
      modest (fivefold or less) differences in expression with growth rate or substrate
      type: sdbA (cellulosomal scaffoldin-dockerin binding protein), cdp (cellodextrin
      phosphorylase), cbp (cellobiose phosphorylase), hydA (hydrogenase), ldh (lactate
      dehydrogenase), ack (acetate kinase), one putative type IV alcohol dehydrogenase,
      two putative cyclic AMP binding proteins, three putative Hpr-like proteins, and a
      putative Hpr serine kinase. By contrast, four genes displayed >10-fold-reduced
      levels of expression when grown on cellobiose at dilution rates of >0.05 h(-1):
      cipA (cellulosomal scaffolding protein), celS (exoglucanase), manA (mannanase),
      and a second type IV alcohol dehydrogenase. The data suggest that at least some
      cellulosomal components are transcriptionally regulated but that differences in
      expression with growth rate or among substrates do not directly account for
      observed changes in fermentation end product distribution.

PMID- 16085863
TI  - Genetic diversity of viable, injured, and dead fecal bacteria assessed by
      fluorescence-activated cell sorting and 16S rRNA gene analysis.
AB  - A novel approach combining a flow cytometric in situ viability assay with 16S
      rRNA gene analysis was used to study the relationship between diversity and
      activity of the fecal microbiota. Simultaneous staining with propidium iodide
      (PI) and SYTO BC provided clear discrimination between intact cells (49%),
      injured or damaged cells (19%), and dead cells (32%). The three subpopulations
      were sorted and characterized by denaturing gradient gel electrophoresis (DGGE)
      of 16S rRNA gene amplicons obtained from the total and bifidobacterial
      communities. This analysis revealed that not only the total community but also
      the distinct subpopulations are characteristic for each individual. Cloning and
      sequencing of the dominant bands of the DGGE patterns showed that most of clones
      retrieved from the live, injured, and dead fractions belonged to Clostridium
      coccoides, Clostridium leptum, and Bacteroides. We found that some of the
      butyrate-producing related bacteria, such as Eubacterium rectale and Eubacterium
      hallii, were obviously viable at the time of sampling. However, amplicons
      affiliated with Bacteroides and Ruminococcus obeum- and Eubacterium biforme-like
      bacteria, as well as Butyrivibrio crossotus, were obtained especially from the
      dead population. Furthermore, some bacterial clones were recovered from all
      sorted fractions, and this was especially noticeable for the Clostridium leptum
      cluster. The bifidobacterial phylotypes identified in total samples and sorted
      fractions were assigned to Bifidobacterium adolescentis, Bifidobacterium longum,
      Bifidobacterium infantis, Bifidobacterium pseudocatenulatum, and Bifidobacterium
      bifidum. Phylogenetic analysis of the live, dead, and injured cells revealed a
      remarkable physiological heterogeneity within these bacterial populations; B.
      longum and B. infantis were retrieved from all sorted fractions, while B.
      adolescentis was recovered mostly from the sorted dead fraction.

PMID- 16085864
TI  - Statistical analyses: possible reasons for unreliability of source tracking
      efforts.
AB  - Analyses for the presence of indicator organisms provide information on the
      microbiological quality of water. Indicator organisms recommended by the United
      States Environmental Protection Agency for monitoring the microbiological quality
      of water include Escherichia coli, a thermotolerant coliform found in the feces
      of warm-blooded animals. These bacteria can also be isolated from environmental
      sources such as the recreational and pristine waters of tropical rain forests in
      the absence of fecal contamination. In the present study, E. coli isolates were
      compared to E. coli K12 (ATCC 29425) by restriction fragment length polymorphism
      using pulsed-field gel electrophoresis. Theoretically, genomic DNA patterns
      generated by PFGE are highly specific for the different isolates of an organism
      and can be used to identify variability between environmental and fecal isolates.
      Our results indicate a different band pattern for almost every one of the E. coli
      isolates analyzed. Cluster analysis did not show any relations between isolates
      and their source of origin. Only the discriminant function analysis grouped the
      samples with the source of origin. The discrepancy observed between the cluster
      analysis and discriminant function analysis relies on their mathematical basis.
      Our validation analyses indicate the presence of an artifact (i.e., grouping of
      environmental versus fecal samples as a product of the statistical analyses used
      and not as a result of separation in terms of source of origin) in the
      classification results; therefore, the large genetic heterogeneity observed in
      these E. coli populations makes the grouping of isolates by source rather
      difficult, if not impossible.

PMID- 16085865
TI  - Study of Spanish grape mycobiota and ochratoxin A production by Isolates of
      Aspergillus tubingensis and other members of Aspergillus section Nigri.
AB  - The native mycobiota of five grape varieties grown in Spain has been studied.
      Four (Bobal, Tempranillo, Garnacha, and Monastrell) were red varieties and one
      (Moscatel) was white. The main fungal genera isolated were Alternaria,
      Cladosporium, and Aspergillus. The isolation frequency of Aspergillus spp.
      section Nigri in contaminated samples was 82%. Ochratoxin A (OTA) production was
      assessed using yeast extract-sucrose broth supplemented with 5% bee pollen.
      Cultures of 205 isolates from this section showed that 74.2% of Aspergillus
      carbonarius and 14.3% of Aspergillus tubingensis isolates produced OTA at levels
      ranging from 1.2 to 3,530 ng/ml and from 46.4 to 111.5 ng/ml, respectively. No
      Aspergillus niger isolate had the ability to produce this toxin under the
      conditions assayed. Identification of the A. niger aggregate isolates was based
      on PCR amplification of 5.8S rRNA genes and its two intergenic spacers, internal
      transcribed spacer 1 (ITS1) and ITS2, followed by digestion with restriction
      endonuclease RsaI of the PCR products. The restriction patterns were compared
      with those from strains of A. niger CECT 2807 and A. tubingensis CECT 20393, held
      at the Spanish Collection of Type Cultures. DNA sequencing of the ITS1-5.8S rRNA
      gene-ITS2 region of the OTA-producing isolates of A. tubingensis matched 99 to
      100% with the nucleotide sequence of strain A. tubingensis CBS 643.92. OTA
      determination was accomplished by liquid chromatography with fluorescence
      detection. OTA confirmation was carried out by liquid chromatography coupled to
      ion trap mass spectrometry. The results showed that there are significant
      differences with regard to the isolation frequency of ochratoxinogenic fungi in
      the different grape varieties. These differences were uncorrelated to berry
      color. The ability of A. tubingensis to produce OTA and the influence of grape
      variety on the occurrence of OTA-producing fungi in grapes are described in this
      report for the first time.

PMID- 16085866
TI  - Proteins encoded by Sphingomonas elodea ATCC 31461 rmlA and ugpG genes, involved
      in gellan gum biosynthesis, exhibit both dTDP- and UDP-glucose pyrophosphorylase
      activities.
AB  - The commercial gelling agent gellan is a heteropolysaccharide produced by
      Sphingomonas elodea ATCC 31461. In this work, we carried out the biochemical
      characterization of the enzyme encoded by the first gene (rmlA) of the rml 4-gene
      cluster present in the 18-gene cluster required for gellan biosynthesis (gel
      cluster). Based on sequence homology, the putative rml operon is presumably
      involved in the biosynthesis of dTDP-rhamnose, the sugar necessary for the
      incorporation of rhamnose in the gellan repeating unit. Heterologous RmlA was
      purified as a fused His6-RmlA protein from extracts prepared from Escherichia
      coli IPTG (isopropyl-beta-D-thiogalactopyranoside)-induced cells, and the protein
      was proven to exhibit dTDP-glucose pyrophosphorylase (Km of 12.0 microM for dTDP
      glucose) and UDP-glucose pyrophosphorylase (Km of 229.0 microM for UDP-glucose)
      activities in vitro. The N-terminal region of RmlA exhibits the motif G-X-G-T-R
      X2-P-X-T, which is highly conserved among bacterial XDP-sugar pyrophosphorylases.
      The motif E-E-K-P, with the conserved lysine residue (K163) predicted to be
      essential for glucose-1-phosphate binding, was observed. The S. elodea ATCC 31461
      UgpG protein, encoded by the ugpG gene which maps outside the gel cluster, was
      previously identified as the UDP-glucose pyrophosphorylase involved in the
      formation of UDP-glucose, also required for gellan synthesis. In this study, we
      demonstrate that UgpG also exhibits dTDP-glucose pyrophosphorylase activity in
      vitro and compare the kinetic parameters of the two proteins for both substrates.
      DNA sequencing of ugpG gene-adjacent regions and sequence similarity studies
      suggest that this gene maps with others involved in the formation of sugar
      nucleotides presumably required for the biosynthesis of another cell
      polysaccharide(s).

PMID- 16085867
TI  - Engineering of phenylacetaldehyde reductase for efficient substrate conversion in
      concentrated 2-propanol.
AB  - Phenylacetaldehyde reductase (PAR) is suitable for the conversion of various aryl
      ketones and 2-alkanones to corresponding chiral alcohols. 2-Propanol acts as a
      substrate solvent and hydrogen donor of coupled cofactor regeneration during the
      conversion of substrates catalyzed by PAR. To improve the conversion efficiency
      in high concentrations of substrate and 2-propanol, selection of a PAR mutant
      library and the subsequent rearrangement of mutations were attempted. With only a
      single selection round and following the manual combination of advantageous
      mutations, PAR was successfully adapted for the conversion of high concentrations
      of substrate with concentrated 2-propanol. This method will be widely applicable
      for the engineering of enzymes potentially valuable for industry.

PMID- 16085868
TI  - Suicide polymerase endonuclease restriction, a novel technique for enhancing PCR
      amplification of minor DNA templates.
AB  - PCR-based molecular analyses can be hindered by the presence of unwanted or
      dominant DNA templates that reduce or eliminate detection of alternate templates.
      We describe here a reaction in which such templates can be exclusively digested
      by endonuclease restriction, leaving all other DNAs unmodified. After such a
      modification, the digested template is no longer available for PCR amplification,
      while nontarget DNAs remain intact and can be amplified. We demonstrate the
      application of this method and use denaturing gradient gel electrophoresis to
      ascertain the removal of target DNA templates and the subsequent enhanced
      amplification of nondigested DNAs. Specifically, plastid 16S rRNA genes were
      exclusively digested from environmental DNA extracted from plant roots. In
      addition, pure culture and environmental DNA extracts were spiked with various
      amounts of genomic DNA extracted from Streptomyces spp., and selective
      restriction of the Streptomyces 16S rRNA genes via the suicide polymerase
      endonuclease restriction PCR method was employed to remove the amended DNA.

PMID- 16085869
TI  - Biological control of hog waste odor through stimulated microbial Fe(III)
      reduction.
AB  - Odor control and disposal of swine waste have inhibited expansion of swine
      production facilities throughout the United States. Swine waste odor is
      associated primarily with high concentrations of volatile fatty acids (VFAs).
      Here, we demonstrate that stimulated Fe(III) reduction in hog manure can rapidly
      remove the malodorous compounds and enhance methane production by 200%. As part
      of these studies, we enumerated the indigenous Fe(III)-reducing population in
      swine waste and identified members of the family Geobacteraceae as the dominant
      species. These organisms were present at concentrations as high as 2 x 10(5)
      cells g(-1). Several pure cultures of Fe(III) reducers, including Geobacter
      metallireducens, Geobacter humireducens, Geobacter sulfurreducens, Geobacter
      grbiciae, Geothrix fermentans, and Geovibrio ferrireducens, readily degraded some
      or all of the malodorous VFAs found in swine manure. In contrast, Shewanella
      algae did not degrade any of these compounds. We isolated an Fe(III) reducer,
      Geobacter strain NU, from materials collected from primary swine waste lagoons.
      This organism degraded all of the malodorous VFAs tested and readily grew in
      swine waste amended with Fe(III). When raw waste amended with Fe(III) was
      inoculated with strain NU, the VFA content rapidly decreased, corresponding with
      an almost complete removal of the odor. In contrast, the raw waste without
      Fe(III) or strain NU showed a marked increase in VFA content and a rapid pH drop.
      This study showed that Fe(III) supplementation combined with appropriate
      bioaugmentation provides a simple, cost-effective approach to deodorize and treat
      swine waste, removing a significant impediment to the expansion of pork
      production facilities.

PMID- 16085870
TI  - Regiospecificity of two multicomponent monooxygenases from Pseudomonas stutzeri
      OX1: molecular basis for catabolic adaptation of this microorganism to methylated
      aromatic compounds.
AB  - The pathways for degradation of aromatic hydrocarbons are constantly modified by
      a variety of genetic mechanisms. Genetic studies carried out with Pseudomonas
      stutzeri OX1 suggested that the tou operon coding for toluene o-xylene
      monooxygenase (ToMO) was recently recruited into a preexisting pathway that
      already possessed the ph operon coding for phenol hydroxylase (PH). This
      apparently resulted in a redundancy of enzymatic activities, because both enzymes
      are able to hydroxylate (methyl)benzenes to (methyl)catechols via the
      intermediate production of (methyl)phenols. We investigated the kinetics and
      regioselectivity of toluene and o-xylene oxidation using Escherichia coli cells
      expressing ToMO and PH complexes. Our data indicate that in the recombinant
      system the enzymes act sequentially and that their catalytic efficiency and
      regioselectivity optimize the degradation of toluene and o-xylene, both of which
      are growth substrates. The main product of toluene oxidation by ToMO is p-cresol,
      the best substrate for PH, which catalyzes its transformation to 4
      methylcatechol. The sequential action of the two enzymes on o-xylene leads, via
      the intermediate 3,4-dimethylphenol, to the exclusive production of 3,4
      dimethylcatechol, the only dimethylcatechol isomer that can serve as a carbon and
      energy source after further metabolic processing. Moreover, our data strongly
      support a metabolic explanation for the acquisition of the ToMO operon by P.
      stutzeri OX1. It is possible that using the two enzymes in a concerted fashion
      confers on the strain a selective advantage based on the ability of the
      microorganism to optimize the efficiency of the use of nonhydroxylated aromatic
      hydrocarbons, such as benzene, toluene, and o-xylene.

PMID- 16085871
TI  - Mutation of glutamic acid 103 of toluene o-xylene monooxygenase as a means to
      control the catabolic efficiency of a recombinant upper pathway for degradation
      of methylated aromatic compounds.
AB  - Toluene o-xylene monooxygenase (ToMO) and phenol hydroxylase (PH) of Pseudomonas
      stutzeri OX1 act sequentially in a recombinant upper pathway for the degradation
      of aromatic hydrocarbons. The catalytic efficiency and regioselectivity of these
      enzymes optimize the degradation of growth substrates like toluene and o-xylene.
      For example, the sequential monooxygenation of o-xylene by ToMO and PH leads to
      almost exclusive production of 3,4-dimethylcatechol (3,4-DMC), the only isomer
      that can be further metabolized by the P. stutzeri meta pathway. We investigated
      the possibility of producing ToMO mutants with modified regioselectivity compared
      with the regioselectivity of the wild-type protein in order to alter the ability
      of the recombinant upper pathway to produce methylcatechol isomers from toluene
      and to produce 3,4-DMC from o-xylene. The combination of mutant (E103G)-ToMO and
      PH increased the production of 4-methylcatechol from toluene and increased the
      formation of 3,4-DMC from o-xylene. These data strongly support the idea that the
      products and efficiency of the metabolic pathway can be controlled not only
      through mutations that increase the catalytic efficiency of the enzymes involved
      but also through tuning the substrate specificity and regioselectivity of the
      enzymes. These findings are crucial for the development of future metabolic
      engineering strategies.

PMID- 16085872
TI  - Cultivation of mesophilic soil crenarchaeotes in enrichment cultures from plant
      roots.
AB  - Because archaea are generally associated with extreme environments, detection of
      nonthermophilic members belonging to the archaeal division Crenarchaeota over the
      last decade was unexpected; they are surprisingly ubiquitous and abundant in
      nonextreme marine and terrestrial habitats. Metabolic characterization of these
      nonthermophilic crenarchaeotes has been impeded by their intractability toward
      isolation and growth in culture. From studies employing a combination of
      cultivation and molecular phylogenetic techniques (PCR-single-strand conformation
      polymorphism, sequence analysis of 16S rRNA genes, fluorescence in situ
      hybridization, and real-time PCR), we present evidence here that one of the two
      dominant phylotypes of Crenarchaeota that colonizes the roots of tomato plants
      grown in soil from a Wisconsin field is selectively enriched in mixed cultures
      amended with root extract. Clones recovered from enrichment cultures were found
      to group phylogenetically with sequences from clade C1b.A1. This work
      corroborates and extends our recent findings, indicating that the diversity of
      the crenarchaeal soil assemblage is influenced by the rhizosphere and that
      mesophilic soil crenarchaeotes are found associated with plant roots, and
      provides the first evidence for growth of nonthermophilic crenarchaeotes in
      culture.

PMID- 16085873
TI  - Nonpathogenic strains of Colletotrichum lindemuthianum trigger progressive bean
      defense responses during appressorium-mediated penetration.
AB  - The fungal bean pathogen Colletotrichum lindemuthianum differentiates appressoria
      in order to penetrate bean tissues. We showed that appressorium development in C.
      lindemuthianum can be divided into three stages, and we obtained three
      nonpathogenic strains, including one strain blocked at each developmental stage.
      H18 was blocked at the appressorium differentiation stage; i.e., no genuine
      appressoria were formed. H191 was blocked at the appressorium maturation stage;
      i.e., appressoria exhibited a pigmentation defect and developed only partial
      internal turgor pressure. H290 was impaired in appressorium function; i.e.,
      appressoria failed to penetrate into bean tissues. Furthermore, these strains
      could be further discriminated according to the bean defense responses that they
      induced. Surprisingly, appressorium maturation, but not appressorium function,
      was sufficient to induce most plant defense responses tested (superoxide ion
      production and strong induction of pathogenesis-related proteins). However,
      appressorium function (i.e., entry into the first host cell) was necessary for
      avirulence-mediated recognition of the fungus.

PMID- 16085874
TI  - Novel AroA with high tolerance to glyphosate, encoded by a gene of Pseudomonas
      putida 4G-1 isolated from an extremely polluted environment in China.
AB  - Glyphosate has been used globally as a safe herbicide for weed control. It
      inhibits 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase (AroA), which is a
      key enzyme in the aromatic amino acid biosynthetic pathway in microorganisms and
      plants. A Pseudomonas putida strain, 4G-1, was isolated from a soil heavily
      contaminated by glyphosate in China. Its AroA-encoding gene (aroA) has been
      cloned, sequenced, and expressed in Escherichia coli. Phylogenetic analysis
      revealed that this AroA belongs neither to class I nor to class II AroA enzymes.
      When compared with E. coli AroA, 4G-1 AroA shows similar values for K(m)[PEP],
      K(m)[S3P], and specific enzyme activity. Moreover, 4G-1 AroA exhibits high
      tolerance to glyphosate, which indicates a protein with a high potential for
      structural and functional studies of AroA in general and its potential usage for
      the generation of transgenic crops resistant to the herbicide.

PMID- 16085876
TI  - Single-nucleotide polymorphism phylotyping of Escherichia coli.
AB  - We describe a rapid and easily automated phylogenetic grouping technique based on
      analysis of bacterial genome single-nucleotide polymorphisms (SNPs). We selected
      13 SNPs derived from a complete sequence analysis of 11 essential genes
      previously used for multilocus sequence typing (MLST) of 30 Escherichia coli
      strains representing the genetic diversity of the species. The 13 SNPs were
      localized in five genes, trpA, trpB, putP, icdA, and polB, and were selected to
      allow recovery of the main phylogenetic groups (groups A, B1, E, D, and B2) and
      subgroups of the species. In the first step, we validated the SNP approach in
      silico by extracting SNP data from the complete sequences of the five genes for a
      panel of 65 pathogenic strains belonging to different E. coli pathovars, which
      were previously analyzed by MLST. In the second step, we determined these SNPs by
      dideoxy single-base extension of unlabeled oligonucleotide primers for a
      collection of 183 commensal and extraintestinal clinical E. coli isolates and
      compared the SNP phylotyping method to previous well-established typing methods.
      This SNP phylotyping method proved to be consistent with the other methods for
      assigning phylogenetic groups to the different E. coli strains. In contrast to
      the other typing methods, such as multilocus enzyme electrophoresis, ribotyping,
      or PCR phylotyping using the presence/absence of three genomic DNA fragments, the
      SNP typing method described here is derived from a solid phylogenetic analysis,
      and the results obtained by this method are more meaningful. Our results indicate
      that similar approaches may be used for a wide variety of bacterial species.

PMID- 16085875
TI  - Effect of pH on an in vitro model of gastric microbiota in enteral nutrition
      patients.
AB  - Patients with dysphagia due to oropharyngeal disease or cerebrovascular accident
      require long-term nutritional support via enteral feeding, which often results in
      microbial overgrowth in the upper gastrointestinal (GI) tract. Gastric acid is
      the primary innate defense mechanism in the stomach and has been assumed to
      provide an effective barrier to microbial colonization at pH values of <4. To
      evaluate the efficacy of gastric acid as a barrier to overgrowth, the microbiota
      of gastric and duodenal aspirates was assessed by culturing methods.
      Additionally, a fermentor-based model incorporating enteral nutrition tubing of
      the gastric microbiota of enteral nutrition (EN) patients was constructed to
      assess the effect of pH on the microbiota. Results showed that gastric acidity
      had a relatively small effect on the numbers of microorganisms recovered from
      intestinal aspirates but did influence microbiota composition. Similarly, at pH 3
      in the fermentor, a complex microbiota developed in the planktonic phase and in
      biofilms. The effect of pH on microbiota composition was similar in aspirates and
      in the fermentors. Candidas and lactobacilli were aciduric, while recoveries of
      Escherichia coli and Klebsiella pneumoniae decreased as pH was reduced, although
      both were still present in significant numbers at pH 3. Only Staphylococcus
      aureus and Bifidobacterium adolescentis persisted at higher pH values both in
      vitro and in vivo. Lactate and acetate were the main organic acids detected in
      both aspirates and fermentors. These data show that the simulator used in this
      investigation was capable of modeling the effects of environmental influences on
      the upper GI microbiota of EN patients and that gastric pH of <4 is not
      sufficient to prevent microbial overgrowth in these individuals.

PMID- 16085877
TI  - Culturability and coexistence of colony-forming and single-cell marine
      bacterioplankton.
AB  - Culturability and coexistence of bacterioplankton exhibiting different life
      strategies were investigated in the Baltic Sea and Skagerrak Sea. Bacterial
      numbers were estimated using a dilution-to-extinction culturing assay (DCA) and
      calculated as the most probable number, based on six different methods to detect
      bacterial growth in the DCA. Irrespective of the method used to detect growth,
      the fraction of multiplying cells never exceeded 10%, using the total count of
      4',6'-diamidino-2-phenylindole (DAPI)-stainable cells as a reference.
      Furthermore, the data also showed that non-colony-forming bacteria made up the
      majority of the viable cells, confirming molecular results showing dominance of
      non-colony-forming bacteria in clone libraries. The results obtained are in
      agreement with previous observations, indicating that bacterial assemblages in
      seawater are dominated by small, active subpopulations coexisting with a large
      group of inactive cells. The ratio of colony-forming to non-colony-forming
      bacteria was approximately 10 to 20 times higher in the brackish Baltic Sea than
      in the Skagerrak Sea. These two sea areas differ in (for example) their levels of
      bacterial production, dissolved organic carbon, and salinity. We suggest that the
      relative importance of colony-forming versus non-colony-forming bacterioplankton
      may be linked to environmental characteristics.

PMID- 16085878
TI  - Optically transparent porous medium for nondestructive studies of microbial
      biofilm architecture and transport dynamics.
AB  - We describe a novel and noninvasive, microscopy-based method for visualizing the
      structure and dynamics of microbial biofilms, individual fluorescent microbial
      cells, and inorganic colloids within a model porous medium. Biofilms growing in
      flow cells packed with granules of an amorphous fluoropolymer could be visualized
      as a consequence of refractive index matching between the solid fluoropolymer
      grains and the aqueous immersion medium. In conjunction with the capabilities of
      confocal microscopy for nondestructive optical sectioning, the use of amorphous
      fluoropolymers as a solid matrix permits observation of organisms and dynamic
      processes to a depth of 2 to 3 mm, whereas sediment biofilms growing in sand
      filled flow cells can only be visualized in the region adjacent to the flow cell
      wall. This method differs fundamentally from other refractive index-matching
      applications in that optical transparency was achieved by matching a solid phase
      to water (and not vice versa), thereby permitting real-time microscopic studies
      of particulate-containing, low-refractive-index media such as biological and
      chromatographic systems.

PMID- 16085879
TI  - Characterization of colony morphology variants isolated from Pseudomonas
      aeruginosa biofilms.
AB  - In this study, we report the isolation of small, rough, strongly cohesive colony
      morphology variants from aging Pseudomonas aeruginosa PAO1 biofilms. Similar to
      many of the P. aeruginosa colony morphology variants previously described in the
      literature, these variants autoaggregate in liquid culture and hyperadhere to
      solid surfaces. They also exhibit increased hydrophobicity and reduced motility
      compared to the wild-type parent strain. Despite the similarities in appearance
      of our colony morphology variant isolates on solid medium, the isolates showed a
      range of responses in various phenotypic assays. These variants form biofilms
      with significant three-dimensional structure and more biomass than the wild-type
      parent. To further explore the nature of the variants, their transcriptional
      profiles were evaluated. The variants generally showed increased expression of
      the psl and pel loci, which have been previously implicated in the adherence of
      P. aeruginosa to solid surfaces. When a mutation in the psl locus was introduced
      into a colony morphology variant, the colony morphology was only partially
      affected, but hyperadherence and autoaggregation were lost. Finally, similar
      colony morphology variants were found in isolates from cystic fibrosis patients.
      These variants displayed many of the same characteristics as the laboratory
      variants, suggesting a link between laboratory and cystic fibrosis biofilms.

PMID- 16085881
TI  - Aphid-symbiotic bacteria cultured in insect cell lines.
AB  - The cells and tissues of many aphids contain bacteria known as "secondary
      symbionts," which under specific environmental circumstances may be beneficial to
      the host insect. Such symbiotic bacteria are traditionally described as
      intractable to cultivation in vitro. Here we show that two types of aphid
      secondary symbionts, known informally as T type and U type, can be cultured and
      maintained in three insect cell lines. The identities of the cultured bacteria
      were confirmed by PCR with sequencing of 16S rRNA gene fragments and fluorescence
      in situ hybridization. In cell lines infected with bacteria derived from aphids
      harboring both T type and U type, the U type persisted, while the T type was
      lost. We suggest that the two bacteria persist in aphids because competition
      between them is limited by differences in tropism for insect tissues or cell
      types. The culture of these bacteria in insect cell lines provides a new and
      unique research opportunity, offering a source of unibacterial material for
      genomic studies and a model system to investigate the interactions between animal
      cells and bacteria. We propose the provisional taxon names "Candidatus
      Consessoris aphidicola" for T type and "Candidatus Adiaceo aphidicola" for U
      type.

PMID- 16085880
TI  - Composition and structure of microbial communities from stromatolites of Hamelin
      Pool in Shark Bay, Western Australia.
AB  - Stromatolites, organosedimentary structures formed by microbial activity, are
      found throughout the geological record and are important markers of biological
      history. More conspicuous in the past, stromatolites occur today in a few shallow
      marine environments, including Hamelin Pool in Shark Bay, Western Australia.
      Hamelin Pool stromatolites often have been considered contemporary analogs to
      ancient stromatolites, yet little is known about the microbial communities that
      build them. We used DNA-based molecular phylogenetic methods that do not require
      cultivation to study the microbial diversity of an irregular stromatolite and of
      the surface and interior of a domal stromatolite. To identify the constituents of
      the stromatolite communities, small subunit rRNA genes were amplified by PCR from
      community genomic DNA with universal primers, cloned, sequenced, and compared to
      known rRNA genes. The communities were highly diverse and novel. The average
      sequence identity of Hamelin Pool sequences compared to the >200,000 known rRNA
      sequences was only approximately 92%. Clone libraries were approximately 90%
      bacterial and approximately 10% archaeal, and eucaryotic rRNA genes were not
      detected in the libraries. The most abundant sequences were representative of
      novel proteobacteria (approximately 28%), planctomycetes ( approximately 17%),
      and actinobacteria (approximately 14%). Sequences representative of
      cyanobacteria, long considered to dominate these communities, comprised <5% of
      clones. Approximately 10% of the sequences were most closely related to those of
      alpha-proteobacterial anoxygenic phototrophs. These results provide a framework
      for understanding the kinds of organisms that build contemporary stromatolites,
      their ecology, and their relevance to stromatolites preserved in the geological
      record.

PMID- 16085882
TI  - Metagenomic analysis reveals diverse polyketide synthase gene clusters in
      microorganisms associated with the marine sponge Discodermia dissoluta.
AB  - Sponge-associated bacteria are thought to produce many novel bioactive compounds,
      including polyketides. PCR amplification of ketosynthase domains of type I
      modular polyketide synthases (PKS) from the microbial community of the marine
      sponge Discodermia dissoluta revealed great diversity and a novel group of sponge
      specific PKS ketosynthase domains. Metagenomic libraries totaling more than four
      gigabases of bacterial genomes associated with this sponge were screened for type
      I modular PKS gene clusters. More than 90% of the clones in total sponge DNA
      libraries represented bacterial DNA inserts, and 0.7% harbored PKS genes. The
      majority of the PKS hybridizing clones carried small PKS clusters of one to three
      modules, although some clones encoded large multimodular PKSs (more than five
      modules). The most abundant large modular PKS appeared to be encoded by a
      bacterial symbiont that made up < 1% of the sponge community. Sequencing of this
      PKS revealed 14 modules that, if expressed and active, is predicted to produce a
      multimethyl-branched fatty acid reminiscent of mycobacterial lipid components.
      Metagenomic libraries made from fractions enriched for unicellular or filamentous
      bacteria differed significantly, with the latter containing numerous nonribosomal
      peptide synthetase (NRPS) and mixed NRPS-PKS gene clusters. The filamentous
      bacterial community of D. dissoluta consists mainly of Entotheonella spp., an
      unculturable sponge-specific taxon previously implicated in the biosynthesis of
      bioactive peptides.

PMID- 16085884
TI  - Isolation and characterization of Aspergillus oryzae vacuolar protein sorting
      mutants.
AB  - The vacuolar protein sorting (vps) system in the filamentous fungus Aspergillus
      oryzae, which has unique cell polarity and the ability to secrete large amounts
      of proteins, was evaluated by using mutants that missort vacuolar proteins into
      the medium. Vacuolar carboxypeptidase Y (CPY) fused with enhanced green
      fluorescent protein (EGFP) was used as a vacuolar marker. Twenty dfc (dim EGFP
      fluorescence in conidia) mutants with reduced intracellular EGFP fluorescence in
      conidia were isolated by fluorescence-activated cell sorting from approximately
      20,000 UV-treated conidia. Similarly, 22 hfm (hyper-EGFP fluorescence released
      into the medium) mutants with increased extracellular EGFP fluorescence were
      isolated by using a fluorescence microplate reader from approximately 20,000 UV
      treated conidia. The dfc and hfm mutant phenotypes were pH dependent, and
      missorting of CPY-EGFP could vary by 10- to 40-fold depending on the ambient pH.
      At pH 5.5, the dfc-14 and hfm-4 mutants had an abnormal hyphal morphology that is
      consistent with fragmentation of vacuoles and defects in cell polarity. In
      contrast, the hyphal and vacuolar morphology of the dfc-14 and hfm-4 mutants was
      normal at pH 8.0, although CPY-EGFP accumulated in perivacuolar dot-like
      structures similar to the class E compartments in Saccharomyces cerevisiae vps
      mutants. In hfm-21, CPY-EGFP localized at the Spitzenkorper when the mutant was
      grown at pH 8.0 but not in vacuoles, suggesting that hfm-21 may transport CPY
      EGFP via a novel pathway that involves the Spitzenkorper. Correlations between
      vacuolar protein sorting, pH response, and cell polarity are reported for the
      first time for filamentous fungi.

PMID- 16085883
TI  - Adhesion of Vibrio cholerae to granular starches.
AB  - Cholera is a severe diarrheal disease caused by specific serogroups of Vibrio
      cholerae that are pathogenic to humans. Cholera can become epidemic and deadly
      without adequate medical care. Appropriate rehydration therapy can reduce the
      mortality rate from as much as 50% of the affected individuals to <1%. Thus, oral
      rehydration therapy (ORT) is an important measure in the treatment of this
      disease. To further reduce the symptoms associated with cholera, improvements in
      oral rehydration solution (ORS) by starch incorporation were suggested. Here, we
      report that V. cholerae adheres to starch granules incorporated in ORS. Adhesion
      of 98% of the cells was observed within 2 min when cornstarch granules were used.
      Other starches showed varied adhesion rates, indicating that starch source and
      composition play an important role in the interaction of V. cholerae and starch
      granules. Sugars metabolized by V. cholerae showed a repressive effect on the
      adhesion process. The possible mechanisms involved are discussed. Comparing V.
      cholerae adhesion with the adhesion of other pathogens suggests the involvement
      of starch degradation capabilities. This adhesion to granular starch can be used
      to improve ORT.

PMID- 16085885
TI  - Insights into the biosynthesis of the benzoquinone ansamycins geldanamycin and
      herbimycin, obtained by gene sequencing and disruption.
AB  - Geldanamycin and the closely related herbimycins A, B, and C were the first
      benzoquinone ansamycins to be extensively studied for their antitumor properties
      as small-molecule inhibitors of the Hsp90 protein chaperone complex. These
      compounds are produced by two different Streptomyces hygroscopicus strains and
      have the same modular polyketide synthase (PKS)-derived carbon skeleton but
      different substitution patterns at C-11, C-15, and C-17. To set the stage for
      structural modification by genetic engineering, we previously identified the gene
      cluster responsible for geldanamycin biosynthesis. We have now cloned and
      sequenced a 115-kb segment of the herbimycin biosynthetic gene cluster from S.
      hygroscopicus AM 3672, including the genes for the PKS and most of the post-PKS
      tailoring enzymes. The similarities and differences between the gene clusters and
      biosynthetic pathways for these closely related ansamycins are interpreted with
      support from the results of gene inactivation experiments. In addition, the
      organization and functions of genes involved in the biosynthesis of the 3-amino-5
      hydroxybenzoic acid (AHBA) starter unit and the post-PKS modifications of
      progeldanamycin were assessed by inactivating the subclusters of AHBA
      biosynthetic genes and two oxygenase genes (gdmM and gdmL) that were proposed to
      be involved in formation of the geldanamycin benzoquinoid system. A resulting
      novel geldanamycin analog, KOS-1806, was isolated and characterized.

PMID- 16085886
TI  - Escherichia coli K1's capsule is a barrier to bacteriophage T7.
AB  - Escherichia coli strains that produce the K1 polysaccharide capsule have long
      been associated with pathogenesis. This capsule is believed to increase the
      cell's invasiveness, allowing the bacteria to avoid phagocytosis and inactivation
      by complement. It is also recognized as a receptor by some phages, such as K1F
      and K1-5, which have virion-associated enzymes that degrade the polysaccharide.
      In this report we show that expression of the K1 capsule in E. coli physically
      blocks infection by T7, a phage that recognizes lipopolysaccharide as the primary
      receptor. Enzymatic removal of the K1 antigen from the cell allows T7 to adsorb
      and replicate. This observation suggests that the capsule plays an important role
      as a defense against some phages that recognize structures beneath it and that
      the K1-specific phages evolved to counter this physical barrier.

PMID- 16085887
TI  - Presence and characterization of a mosaic genomic island which distinguishes
      sorbitol-fermenting enterohemorrhagic Escherichia coli O157:H- from E. coli
      O157:H7.
AB  - A mosaic genomic island comprising Shigella resistance locus (SRL) sequences
      flanked by segments of Escherichia coli O157:H7 strain EDL933 O islands 43, 81,
      and 82 was identified in sorbitol-fermenting (SF) enterohemorrhagic Escherichia
      coli (EHEC) O157:H(-) strain 493/89. This mosaic island is absent from strain
      EDL933. PCR targeting the SRL-related sequence is a useful tool to distinguish SF
      EHEC O157:H(-) from EHEC O157:H7.

PMID- 16085889
TI  - Correlation of Campylobacter bacteriophage with reduced presence of hosts in
      broiler chicken ceca.
AB  - Campylobacter jejuni and Campylobacter-specific bacteriophage were enumerated
      from broiler chicken ceca selected from 90 United Kingdom flocks (n = 205). C.
      jejuni counts in the presence of bacteriophage (mean log(10) 5.1 CFU/g) were
      associated with a significant (P < 0.001) reduction compared to samples with
      Campylobacter alone (mean log(10) 6.9 CFU/g).

PMID- 16085888
TI  - Novel approach to quantitative detection of specific rRNA in a microbial
      community, using catalytic DNA.
AB  - We developed a novel method for the quantitative detection of the 16S rRNA of a
      specific bacterial species in the microbial community by using deoxyribozyme
      (DNAzyme), which possesses the catalytic function to cleave RNA in a sequence
      specific manner. A mixture of heterogeneous 16S rRNA containing the target 16S
      rRNA was incubated with a species-specific DNAzyme. The cleaved target 16S rRNA
      was separated from the intact 16S rRNA by electrophoresis, and then their amounts
      were compared for the quantitative detection of target 16S rRNA. This method was
      used to determine the abundance of the 16S rRNA of a filamentous bacterium,
      Sphaerotilus natans, in activated sludge, which is a microbial mixture used in
      wastewater treatment systems. The result indicated that this DNAzyme-based
      approach would be applicable to actual microbial communities.

PMID- 16085890
TI  - Multilocus simple sequence repeat markers for differentiating strains and
      evaluating genetic diversity of Xylella fastidiosa.
AB  - A genome-wide search was performed to identify simple sequence repeat (SSR) loci
      among the available sequence databases from four strains of Xylella fastidiosa
      (strains causing Pierce's disease, citrus variegated chlorosis, almond leaf
      scorch, and oleander leaf scorch). Thirty-four SSR loci were selected for SSR
      primer design and were validated in PCR experiments. These multilocus SSR
      primers, distributed across the X. fastidiosa genome, clearly differentiated and
      clustered X. fastidiosa strains collected from grape, almond, citrus, and
      oleander. They are well suited for differentiating strains and studying X.
      fastidiosa epidemiology and population genetics.

PMID- 16085891
TI  - Fluorophore-labeled primers improve the sensitivity, versatility, and
      normalization of denaturing gradient gel electrophoresis.
AB  - Denaturing gradient gel electrophoresis (DGGE) is widely used in microbial
      ecology. We tested the effect of fluorophore-labeled primers on DGGE band
      migration, sensitivity, and normalization. The fluorophores Cy5 and Cy3 did not
      visibly alter DGGE fingerprints; however, 6-carboxyfluorescein retarded band
      migration. Fluorophore modification improved the sensitivity of DGGE fingerprint
      detection and facilitated normalization of samples from multiple gels by the
      application of intralane standards.

PMID- 16085892
TI  - Insertional inactivation of determinants for Mg2+ and Co2+ transport as a tool
      for screening recombinant Lactococcus species clones.
AB  - Insertional inactivation of the plasmid-encoded determinants for Mg(2+) and
      Co(2+) transport, orf18/corA, provides a tool for screening recombinant clones in
      Lactococcus, based on the observation that overexpression of orf18/corA results
      in cell growth inhibition on certain concentrations of CoCl(2). The lacticin 3147
      immunity gene, ltnI, was used to insertionally inactivate orf18/corA. The
      resulting clones were capable of growth on concentrations of CoCl(2) that were
      inhibitory to the parent strain. Since only 3 of 17 lactococcal starters
      naturally harbor corA, the system has potential as a screen for selecting
      recombinant lactococcal clones.

PMID- 16085893
TI  - Habits of magnetosome crystals in coccoid magnetotactic bacteria.
AB  - High-resolution transmission electron microscopy and electron holography were
      used to study the habits of exceptionally large magnetite crystals in coccoid
      magnetotactic bacteria. In addition to the crystal habits, the crystallographic
      positioning of successive crystals in the magnetosome chain appears to be under
      strict biological control.

PMID- 16085894
TI  - Identification of acyl-homoserine lactone signal molecules produced by
      Nitrosomonas europaea strain Schmidt.
AB  - Nitrosomonas europaea strain Schmidt produces at least three acyl homoserine
      lactone (AHL) signal molecules: C(6)-homoserine lactone (HSL), C(8)-HSL, and
      C(10)-HSL. These compounds were identified in extracts of chemostat culture
      effluent by three independent methods. The concentrations of AHL in effluent were
      low (0.4 to 2.2 nM) but within the range known to induce AHL-responsive systems.
      The absence of LuxI and LuxM homologs from the genome of N. europaea strain
      Schmidt suggested that AHL synthesis occurs by an alternate pathway, possibly
      mediated by an HdtS homolog. To the best of our knowledge, the present report is
      the first to document the types and levels of AHLs produced by N. europaea.

PMID- 16085895
TI  - Transcriptome-based identification of the Sinorhizobium meliloti NodD1 regulon.
AB  - The NodD1 regulon of Sinorhizobium meliloti was determined through the analysis
      of the S. meliloti transcriptome in response to the plant flavone luteolin and
      the overexpression of nodD1. Nine new genes regulated by both NodD1 and luteolin
      were identified, demonstrating that NodD1 controls few functions behind
      nodulation in S. meliloti.

PMID- 16085896
TI  - Development of a plasmid-mediated reporter system for in vivo monitoring of gene
      expression in the archaeon Methanosarcina acetivorans.
AB  - A plasmid-based gene reporter system has been developed to construct lacZ gene
      fusions for monitoring intrinsic promoter expression in Methanosarcina
      acetivorans. Constructs transform with high efficiency that can be readily
      screened by color selection on plates and exhibit a consistent copy number on
      different substrates negating the need for gene copy normalization. Expression of
      the CO dehydrogenase-acetyl coenzyme A synthase promoter fusion to lacZ revealed
      18- to 54-fold down-regulation in cells grown on methylotrophic substrates
      compared with acetate-grown cells, which is up to an order of magnitude greater
      than the range of regulation previously reported by enzyme activity assays. This
      system complements and expands the current techniques for studying genetics of
      the methanosarcinal Archaea by providing a rapid method for monitoring and
      quantifying gene expression.

PMID- 16085897
TI  - Development of PCR assays targeting genes in O-antigen gene clusters for
      detection and identification of Escherichia coli O45 and O55 serogroups.
AB  - The Escherichia coli O45 O-antigen gene cluster of strain O45:H2 96-3285 was
      sequenced, and conventional (singleplex), multiplex, and real-time PCR assays
      were designed to amplify regions in the wzx (O-antigen flippase) and wzy (O
      antigen polymerase) genes. In addition, PCR assays targeting the E. coli O55 wzx
      and wzy genes were designed based on previously published sequences. PCR assays
      targeting E. coli O45 showed 100% specificity for this serogroup, whereas by PCR
      assays specific for E. coli O55, 97/102 strains serotyped as E. coli O55 were
      positive for wzx and 98/102 for wzy. Multiplex PCR assays targeting the E. coli
      O45 and the E. coli O55 wzx and wzy genes were used to detect the organisms in
      fecal samples spiked at levels of 10(6) and 10(8) CFU/0.2 g feces. Thus, the PCR
      assays can be used to detect and identify E. coli serogroups O45 and O55.

PMID- 16085898
TI  - Genetic analysis of two bile salt hydrolase activities in Lactobacillus
      acidophilus NCFM.
AB  - Two genes, bshA and bshB, encoding bile salt hydrolase enzymes (EC 3.5.1.24) were
      identified in the genome sequence of Lactobacillus acidophilus NCFM. Targeted
      inactivation of these genes via chromosomal insertion of an integration vector
      demonstrated different substrate specificities for these two enzymes.

PMID- 16085899
TI  - Distribution of the ermG gene among bacterial isolates from porcine intestinal
      contents.
AB  - The ermG gene was first found in the soil bacterium Bacillus sphaericus. More
      recently, it was found in several human intestinal Bacteroides species. We report
      here the first finding of ermG genes in gram-positive bacteria isolated from
      porcine feces and from under-barn manure pits used to store porcine wastes. The
      porcine ermG sequences were identical to the sequence of the B. sphaericus ermG
      gene except that six of the seven ermG-containing strains contained an insertion
      sequence element insertion in the C-terminal end of the gene. The porcine ermG
      genes were found in three different gram-positive genera, an indication that it
      is possible that the gene is being spread by horizontal gene transfer. A segment
      of a Bacteroides conjugative transposon that carries an ermG gene cross
      hybridized with DNA from six of the seven porcine isolates, but the restriction
      patterns in the porcine strains were different from that of the Bacteroides
      conjugative transposon.

PMID- 16085900
TI  - Identification of genes involved in cytochrome c biogenesis in Shewanella
      oneidensis, using a modified mariner transposon.
AB  - A modified mariner transposon, miniHimar RB1, was generated to mutagenize cells
      of the metal-reducing bacterium Shewanella oneidensis. The use of this transposon
      led to the isolation of stable mutants and allowed rapid identification of
      disrupted genes. Fifty-eight mutants, including BG104 and BG148 with transposon
      insertions in the cytochrome c maturation genes ccmC and ccmF1, respectively,
      were analyzed. Both mutants were deficient in anaerobic respiration and
      cytochrome c production.

PMID- 16085901
TI  - Farnesol concentrations required to block germ tube formation in Candida albicans
      in the presence and absence of serum.
AB  - Concentrations of (E,E)-farnesol needed to inhibit germ tube formation were
      determined for Candida albicans strains A72 and SC5314 by using six different
      conditions known to trigger germination. For defined media, 1 to 2 microM
      farnesol was sufficient. However, with serum at 2 to 20%, up to 250 microM
      farnesol was required. Farnesol blocked germ tube formation but did not block
      elongation of existing germ tubes.

PMID- 16085902
TI  - Molecular serotyping of Escherichia coli O26:H11.
AB  - Serotyping is the foundation of pathogenic Escherichia coli diagnostics; however,
      few laboratories have this capacity. We developed a molecular serotyping protocol
      that targets, genetically, the same somatic and flagellar antigens of E. coli
      O26:H11 used in traditional serotyping. It correctly serotypes strains untypeable
      by traditional methods, affording primary laboratories serotyping capabilities.

PMID- 16085903
TI  - Specificity of a Bacteroides thetaiotaomicron marker for human feces.
AB  - A bacterial primer set, known to produce a 542-bp amplicon specific for
      Bacteroides thetaiotaomicron, generated this product in PCR with 1 ng of
      extracted DNA from 92% of 25 human fecal samples, 100% of 20 sewage samples, and
      16% of 31 dog fecal samples. The marker was not detected in 1 ng of fecal DNA
      from 61 cows, 35 horses, 44 pigs, 24 chickens, 29 turkeys, and 17 geese.

PMID- 16085904
TI  - Phagocytic activity in human immunodeficiency virus type 1 infection.

PMID- 16085905
TI  - Role of thromboxane A2 in the induction of apoptosis of immature thymocytes by
      lipopolysaccharide.
AB  - Lipopolysaccharide (LPS) causes apoptotic deletion of CD4(+) CD8(+) thymocytes, a
      phenomenon that has been linked to immune dysfunction and poor survival during
      sepsis. Given the abundance of thromboxane-prostanoid (TP) receptors in CD4(+)
      CD8(+) thymocytes and in vitro evidence that thromboxane A(2) (TXA(2)) causes
      apoptosis of these cells, we tested whether enhanced generation of TXA(2) plays a
      role in LPS-induced thymocyte apoptosis. Mice injected with 50 micro LPS
      intraperitoneally displayed a marked increase in generation of TXA(2) and
      prostaglandin E(2) in the thymus as well as apoptotic deletion of CD4(+) CD8(+)
      thymocytes. Administration of indomethacin or rofecoxib inhibited prostanoid
      synthesis but did not affect thymocyte death. In contrast, thymocyte apoptosis in
      response to LPS was significantly attenuated in TP-deficient mice. These studies
      indicate that TXA(2) mediates a portion of apoptotic thymocyte death caused by
      LPS. The absence of an effect of global inhibition of prostanoid synthesis
      suggests a complex role for prostanoids in this model.

PMID- 16085906
TI  - Production of a recombinant major inner capsid protein for serological detection
      of epizootic hemorrhagic disease virus.
AB  - Constructs of the major core protein, designated VP7, from epizootic hemorrhagic
      disease virus (EHDV) type 1 were made by amino- or carboxyl-terminal fusion of a
      six-histidine residue tag to the VP7-1 gene. The resulting fusion proteins were
      produced in a baculovirus expression system and purified by a rapid, one-step
      procedure using nickel-nitrilotriacetic acid technology. A high level of VP7-1
      protein expression was detected with the N-terminal six-histidine tag fusion
      construct and was comparable to the level of expression observed with an untagged
      VP7-1 Bam construct. In contrast, the inclusion of a six-histidine tag at the C
      terminus adversely affected protein expression. The antigenicity of the N
      terminal six-histidine tag EHDV VP7-1 product was identical to that observed with
      the native virus antigen and untagged EHDV VP7-1 recombinant protein, as
      determined by reactivity with EHDV specific antibodies in an enzyme-linked
      immunosorbent assay (ELISA) and Western blot. The high production and purity
      levels that can be attained for the N-terminal six-histidine tag VP7-1 protein
      and its reactivity with EHDV-specific sera in a competitive ELISA make it a
      suitable assay reagent.

PMID- 16085907
TI  - Critical evaluation of urine-based PCR assay for diagnosis of Lyme borreliosis.
AB  - Many approaches were made in recent years to establish urine PCR as a diagnostic
      tool for Lyme borreliosis, but results are contradictory. In the present study, a
      standardized protocol spiking urine from healthy donors with a defined amount of
      whole Borrelia or Borrelia DNA was established. The development of a nested real
      time PCR targeting ospA enabled a highly sensitive and quantitative analysis of
      these samples. We show the following. (i) Storage of spiked urine samples for up
      to 6 months at--20 degrees C had no negative effect on spike recovery. (ii)
      Centrifugation of 10 ml of urine at 40,000 x g for 30 min resulted in a
      concentration of both spikes, i.e., whole Borrelia and DNA. (iii) The inhibition
      of DNA spike recovery in 48% (11 of 23 samples) of urine samples tested could be
      attributed to nuclease activity. This was abrogated by alkalizing the urine or by
      working with the samples on ice. Despite optimized conditions, analysis of urine
      samples of 12 patients with erythema migrans, the clinical stage considered to be
      associated with the highest bacterial load, revealed a positive result in only
      one sample. All 12 samples were negative by an alternative PCR targeting
      flagellin. The results of our study support doubts that urine is a suitable
      material for diagnosis of Lyme borreliosis.

PMID- 16085908
TI  - Modification of rapid human immunodeficiency virus (HIV) antibody assay protocols
      for detecting recent HIV seroconversion.
AB  - Assay protocols of three rapid human immunodeficiency virus (HIV) assays,
      OraQuick-1/2, SeroStrip-1/2, and Determine-1/2, were modified to detect recent
      HIV seroconversion using a higher dilution of serum specimens. Optimal
      predilution of specimens resulted in negative test results during early periods
      of seroconversion (about 6 months), when antibody levels were low. A total of 269
      seropositive specimens from routine HIV type 1 testing and from commercial
      sources (low-titer and seroconversion panels) were tested, and results were
      recorded as negative (score=0) or positive using intensity scores from 0.5 (weak
      positive) to 4 (strongly positive). The same specimens were previously tested by
      a less sensitive (LS) enzyme immunoassay (EIA), Abbott 3A 11-LS, and were
      classified as recent or long-term infections based on the standardized optical
      density (SOD) cutoff of 0.75. Overall concordance of >94% was observed between 3A
      11-LS and modified rapid tests (RT-LSs) for detecting and distinguishing recent
      HIV seroconversion from long-term HIV infection (kappa statistics=0.894 to
      0.901). Moreover, intensity scores on RT-LSs correlated well with median 3A 11-LS
      SOD values (R(2)>0.98). Our results indicate that rapid HIV tests can be modified
      to detect recent seroconversion with results comparable to those from less
      sensitive EIA.

PMID- 16085909
TI  - Noninfectious virus-like particle antigen for detection of swine vesicular
      disease virus antibodies in pigs by enzyme-linked immunosorbent assay.
AB  - An inactivated SVDV antigen is used in current enzyme-linked immunosorbent assays
      (ELISAs) for the detection of antibodies to swine vesicular disease virus (SVDV).
      To develop a noninfectious recombinant alternative, we produced SVDV-like
      particles (VLPs) morphologically and antigenically resembling authentic SVDV
      particles by using a dual baculovirus recombinant, which expresses simultaneously
      the P1 and 3CD protein genes of SVDV under different promoters. Antigenic
      differences between recombinant VLPs and SVDV particles were not statistically
      significant in results obtained with a 5B7-ELISA kit, indicating that the VLPs
      could be used in the place of SVDV antigen in ELISA kits. We developed a blocking
      ELISA using the VLPs and SVDV-specific neutralizing monoclonal antibody 3H10 (VLP
      ELISA) for detection of SVDV serum antibodies in pigs. The VLP-ELISA showed a
      high specificity of 99.9% when tested with pig sera that are negative for SVDV
      neutralization (n=1,041). When tested using sera (n=186) collected periodically
      from pigs (n=19) with experimental infection with each of three different strains
      of SVDV, the VLP-ELISA detected SVDV serum antibodies as early as 3 days
      postinfection and continued to detect the antibodies from all infected pigs until
      termination of the experiments (up to 121 days postinfection). This test
      performance was similar to that of the gold standard virus neutralization test
      and indicates that the VLP-ELISA is a highly specific and sensitive method for
      the detection of SVDV serum antibodies in pigs. This is the first report of the
      production and diagnostic application of recombinant VLPs of SVDV. Further
      potential uses of the VLPs are discussed.

PMID- 16085910
TI  - Naturally acquired antibodies against four Enterococcus faecalis capsular
      polysaccharides in healthy human sera.
AB  - Healthy human sera (HHS) contain naturally acquired enterococcal antibodies which
      promote neutrophil-mediated killing. The target antigens remain unknown. The
      present study used a capsular polysaccharide (CPS)-enzyme-linked immunosorbent
      assay (ELISA) to investigate whether the HHS antibodies of 12 healthy donors
      bound to the CPS of four E. faecalis serotypes (CPS-A to CPS-D) and then employed
      an opsonic-killing assay to determine if these antibodies mediated phagocyte
      dependent killing. All HHS contained immunoglobulin G (IgG) and IgM antibodies
      directed against capsular polysaccharides of the four serotypes. Absorption of
      the sera with homologous and heterologous strains showed a majority of antibodies
      to be cross-reactive among the prototype strains. The susceptibility of the four
      prototype strains to opsonic killing varied. Opsonic killing of CPS-A and CPS-B
      strains was significantly higher than killing of CPS-C and CPS-D strains.
      Absorption studies revealed that the opsonic killing of HHS was only partially
      type specific, with cross-reactivity between CPS-A and CPS-B strains and between
      CPS-C and CPS-D strains. These data indicate that healthy individuals possess
      opsonic antibodies specific for CPS-A and CPS-B but only low titers of opsonic
      antibodies against CPS-C and CPS-D. Titers of opsonic antibodies did not
      correlate with antibody titers measured by ELISA. Whether this lack of
      correlation is due to the low frequency of opsonic antibodies or to increased
      resistance to the opsonophagocytic killing of some serotypes remains to be
      determined.

PMID- 16085911
TI  - Borrelia burgdorferi BmpA, BmpB, and BmpD proteins are expressed in human
      infection and contribute to P39 immunoblot reactivity in patients with Lyme
      disease.
AB  - The Bmp proteins are a paralogous family of chromosomally encoded Borrelia
      burgdorferi lipoproteins. They have similar predicted immunogenicities and
      similar electrophoretic mobilities by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. P39 reactivity against Borrelia burgdorferi lysate in
      immunoblots of Lyme disease patients has long been identified with reactivity to
      BmpA, but responses to other Bmp proteins have not been examined. To determine if
      patients with Lyme disease developed such responses, immunoglobulin G (IgG) anti
      Bmp reactivity in patient and control sera was studied by using soluble
      recombinant Bmp (rBmp) proteins expressed in Escherichia coli. Although some
      patient sera contained IgG immunoblot and immunodot reactivities against all four
      Bmp proteins, analysis of IgG anti-Bmp fine specificity by a competitive enzyme
      linked immunosorbent assay with graded doses of soluble homologous and
      heterologous rBmp proteins showed that only the responses to BmpA, BmpB, and BmpD
      were specific. This suggests that at least three of the four Bmp proteins are
      expressed by B. burgdorferi in infected patients and that specific antibodies to
      them are likely to be present in the P39 band in some patients.

PMID- 16085912
TI  - Prevalence and clinical significance of immunoglobulin A antibodies against
      tissue transglutaminase in patients with diverse chronic liver diseases.
AB  - The prevalence of celiac disease (CD) and the prevalence and clinical
      significance of anti-tissue transglutaminase (tTG) antibodies (tTGAbs) in a large
      series of patients with chronic liver diseases were assessed. We studied 738
      patients (462 with chronic viral hepatitis, 117 with autoimmune liver diseases,
      113 with alcoholic or nonalcoholic fatty liver disease, and 46 with other liver
      disorders) and 1,350 healthy controls (HC). Immunoglobulin A (IgA) tTGAbs were
      measured by enzyme-linked immunosorbent assay and a microsphere-based flow
      cytometric assay. Positive sera were investigated for IgA antiendomysial
      antibodies (EmA). IgA tTGAb-positive subjects were invited to undergo a small
      intestinal biopsy and HLA-DQ allele typing. Four of 1,350 HC (0.3%) tested
      tTGAb(+) EmA(+) and underwent a biopsy (CD confirmation in all). Four of 738
      liver disease patients tested tTGAbs(+) EmA(+) (0.54%; not statistically
      significant). Two were HCV infected (1.24%; not statistically significant), and
      two had transaminasemia of unknown origin. Forty-three patients tested tTGAbs(+)
      EmA(-) (5.8%; P<0.001 compared to HC). Inhibition experiments verified the
      existence of specific IgA anti-tTG reactivity. Twenty-six of 43 patients
      underwent a biopsy (all negative for CD). Binary logistic regression analysis
      revealed age (P=0.008), cirrhosis (P=0.004), alkaline phosphatase (P=0.026), and
      antinuclear antibodies (P=0.012) as independent risk factors for tTGAb reactivity
      among the patients. It was concluded that CD prevalence is the same in HC and
      patients with chronic liver diseases. The prevalence of tTGAbs is higher in
      hepatic patients compared to HC, but their specificity for CD diagnosis in this
      group of patients is low. tTGAbs in patients appear to be associated with the
      presence of autoimmunity, cirrhosis, and cholestasis, irrespective of the origin
      of the liver disease.

PMID- 16085913
TI  - Lipoprotein-dependent and -independent immune responses to spirochetal infection.
AB  - In this study, we used the epidermal suction blister technique, in conjunction
      with multiparameter flow cytometry, to analyze the cellular and cytokine
      responses elicited by intradermal injection of human volunteers with synthetic
      analogs for spirochetal lipoproteins and compared the responses to findings
      previously reported from patients with erythema migrans (EM). Compared with
      peripheral blood (PB), lipopeptides derived from the N termini of the Borrelia
      burgdorferi outer surface protein C and the 17-kDa lipoprotein of Treponema
      pallidum (OspC-L and 17-L, respectively) elicited infiltrates enriched in
      monocytes/macrophages and dendritic cells (DCs) but also containing substantial
      percentages of neutrophils and T cells. Monocytoid (CD11c(+)) and plasmacytoid
      (CD11c(-)) DCs were selectively recruited to the skin in ratios similar to those
      in PB, but only the former expressed the activation/maturation surface markers
      CD80, CD83, and DC-SIGN. Monocytes/macrophages and monocytoid DCs, but not
      plasmacytoid DCs, displayed significant increases in surface expression of Toll
      like receptor 1 (TLR1), TLR2, and TLR4. Staining for CD45RO and CD27 revealed
      that lipopeptides preferentially recruited antigen-experienced T-cell subsets;
      despite their lack of antigenicity, these agonists induced marked T-cell
      activation, as evidenced by surface expression of CD69, CD25, and CD71.
      Lipopeptides also induced significant increases in interleukin 12 (IL-12), IL-10,
      gamma interferon, and most notably IL-6 without corresponding increases in serum
      levels of these cytokines. Although lipopeptides and EM lesional infiltrates
      shared many similarities, differences were noted in a number of immunologic
      parameters. These studies have provided in situ evidence for a prominent
      "lipoprotein effect" during human infection while at the same time helping to
      pinpoint aspects of the cutaneous response that are uniquely driven by
      spirochetal pathogens.

PMID- 16085914
TI  - Optimization and validation of a multiplexed luminex assay to quantify antibodies
      to neutralizing epitopes on human papillomaviruses 6, 11, 16, and 18.
AB  - A human papillomavirus (HPV) multiplexed competitive Luminex immunoassay first
      described by Opalka et al. (D. Opalka, C. E. Lachman, S. A. MacMullen, K. U.
      Jansen, J. F. Smith, N. Chirmule, and M. T. Esser, Clin. Diagn. Lab. Immunol.
      10:108--15, 2003) was optimized and validated for use in epidemiology studies and
      vaccine clinical trials. Optimization increased both the analytical sensitivity
      and the clinical specificity of the assay to more effectively discriminate the
      low-titer antibody response of HPV-infected persons from noninfected individuals.
      The characteristics of the assay that were optimized included monoclonal antibody
      (MAb) specificity, scaling up the conjugation of virus-like particles (VLPs) to
      microspheres, VLP concentration, MAb concentration, sample matrix, sample
      dilution, incubation time, heat inactivation of sample sera, and detergent
      effects on assay buffer. The assay was automated by use of a TECAN Genesis
      Workstation, thus improving assay throughput, reproducibility, and operator
      safety. Following optimization, the assay was validated using several distinct
      serum panels from individuals determined to be at low and high risk for HPV
      infection. The validated assay was then used to determine the clinical serostatus
      cutoff. This high-throughput assay has proven useful for performing epidemiology
      studies and evaluating the efficacy of prophylactic HPV vaccines.

PMID- 16085915
TI  - Interlaboratory standardization of the measurement of serum bactericidal activity
      by using human complement against meningococcal serogroup b, strain 44/76-SL,
      before and after vaccination with the Norwegian MenBvac outer membrane vesicle
      vaccine.
AB  - There is currently no standardized serum bactericidal antibody (SBA) assay for
      evaluating immune responses to meningococcal outer membrane vesicle or protein
      vaccines. Four laboratories, Manchester Health Protection Agency (MC HPA), New
      Zealand Institute of Environmental Science and Research Limited (NZ ESR),
      Norwegian Institute of Public Health (NIPH), and Chiron Vaccines (Chiron),
      measured SBA titers in the same panel of human sera (n=76) from laboratory staff
      (n=21) vaccinated with MenBvac. Blood samples were collected prevaccination,
      prior to each of the three doses of MenBvac given at 6-week intervals, and 6
      weeks following the third dose. Initial results showed a number of discrepancies
      in results between the four participating laboratories. The greatest effect on
      titers appeared to be due to differences among laboratories in the maintenance of
      the meningococcal serogroup B test strain, 44/76-SL. A repeat study was conducted
      using the same frozen isolate (meningococcal serogroup B test strain 44/76-SL),
      freshly distributed to all four laboratories. Using SBA titers from the tilt
      method for all samples, and using MC HPA as the comparator, the results were as
      follows for NZ ESR, NIPH, and Chiron, respectively, using log(10) titers:
      correlation coefficients (r) were 0.966, 0.967, and 0.936; intercepts were 0.08,
      0.15, and 0.17; and slopes were 0.930, 0.851, and 0.891. In both prevaccination
      and postvaccination samples from 15 subjects assayed by all four laboratories,
      similar increases in SBA (fourfold or greater) were observed (for 11, 11, 9, and
      9 subjects for MC HPA, NZ ESR, NIPH, and Chiron, respectively), and similar
      percentages of subjects with SBA titers of>or=4 p revaccination and 6 weeks
      following each dose were found. The SBA assay has been harmonized between the
      four different laboratories with good agreement on seroconversion rates, n-fold
      changes in titers, and percentages of subjects with SBA titers of >or=4.

PMID- 16085916
TI  - Seroreactivity to and avidity for recombinant antigens in toxoplasmosis.
AB  - To improve serodiagnostic methods for the diagnosis of acute toxoplasmosis during
      pregnancy, a new test system has been developed and evaluated based on the use of
      recombinant antigens. Five recombinant Toxoplasma gondii antigens (ROP1, MAG1,
      SAG1, GRA7, and GRA8) were cloned in Escherichia coli, purified, and applied
      directly onto nitrocellulose membranes in a line assay (recomLine Toxoplasma). A
      panel of 102 sera from 25 pregnant women with supposed recent toxoplasmosis and
      from two symptomatic children was compared to a panel of 71 sera from individuals
      with past infection. Both panels were analyzed using a recombinant line assay for
      immunoglobulin G (IgG), IgM, and IgA antibodies and a reference enzyme-linked
      immunosorbent assay. Within the IgM-positive samples, antibodies against ROP1
      were predominant regardless of the infection state. In IgG analysis a
      characteristic antibody pattern was found for very recent infections. This
      pattern changed to a different one during the time course of infection:
      antibodies against GRA7 and GRA8 were characteristic for very early IgG, whereas
      antibodies against SAG1 and MAG1 appeared significantly later. These results were
      further confirmed by determination of the IgG antibody avidity for every single
      recombinant antigen. In the time course of infection, IgG antibodies against the
      early recognized antigens matured significantly earlier than those directed
      against the later antigens did. The IgA patterns did not give reliable
      information about the infection time points. The data revealed that the
      recombinant line assay provides valuable information on the actual state of
      infection, especially during the early infection time points.

PMID- 16085917
TI  - Lymphocyte proliferation responses induced to broadly reactive Th peptides did
      not protect against equine infectious anemia virus challenge.
AB  - The effect of immunization with five lipopeptides, three containing T-helper (Th)
      epitopes and two with both Th and cytotoxic T-lymphocyte (CTL) epitopes, on
      equine infectious anemia virus (EIAV) challenge was evaluated. Peripheral blood
      mononuclear cells from EIAV lipopeptide-immunized horses had significant
      proliferative responses to Th peptides compared with those preimmunization, and
      the responses were attributed to significant responses to peptides Gag from
      positions 221 to 245 (Gag 221-245), Gag 250-269, and Pol 326-347; however, there
      were no consistent CTL responses. The significant proliferative responses in the
      EIAV lipopeptide-immunized horses allowed testing of the hypothesis that Th
      responses to immunization would enhance Th and CTL responses following EIAV
      challenge and lessen the viral load and the severity of clinical disease. The
      EIAV lipopeptide-immunized group did have a significant increase in proliferative
      responses to Th peptides 1 week after virus challenge, whereas the control group
      did not. Two weeks after challenge, a significant CTL response to virus-infected
      cell targets occurred in the EIAV lipopeptide-immunized group compared to that in
      the control group. These Th and CTL responses did not significantly alter either
      the number of viral RNA copies/ml or disease severity. Thus, lipopeptide-induced
      proliferative responses and enhanced Th and CTL responses early after virus
      challenge were unable to control challenge virus load and clinical disease.

PMID- 16085918
TI  - Cytokine expression in pediatric Helicobacter pylori infection.
AB  - Helicobacter pylori infection is one of the most common gastrointestinal
      infections worldwide and almost invariably causes chronic gastritis in the
      infected host. A predominant Th1 profile has been demonstrated in H. pylori
      infected mucosa from adults, but no previous study has evaluated in situ cytokine
      expression in children. We therefore examined expression of proinflammatory, anti
      inflammatory, and regulatory cytokines by immunohistochemistry in cryopreserved
      antral biopsy specimens from 10 H. pylori-infected and 10 uninfected children and
      correlated expression of cytokines with histology scores. Concomitant expression
      of interleukin-8 (IL-8), gamma interferon (IFN-gamma), IL-4, transforming growth
      factor beta, and tumor necrosis factor alpha was seen in 8/10 H. pylori-infected
      cases and in 5/10 noninfected cases; all H. pylori-infected subjects showed
      staining for at least two of the cytokines. The proportion of epithelial cytokine
      specific staining did not differ significantly between the groups, either in
      surface or glandular epithelium. Furthermore, no significant differences were
      noticed between intraepithelial or lamina propria lymphocyte staining in the
      groups. There was, however, a tendency of higher numbers of IFN-gamma- and IL-8
      positive cells in the H. pylori-infected group. IFN-gamma and IL-8 lamina propria
      lymphocyte expression correlated significantly with antrum chronic inflammation,
      but there was no correlation between histology scores and epithelial cytokine
      expression. When the same techniques were used, the cytokine response appeared to
      be smaller in H. pylori-infected children than in adults, and there was no clear
      Th1 dominance. These results therefore suggest a different mucosal
      immunopathology in children. It remains to be determined whether the gastric
      immune response is downregulated in children with H. pylori infection and whether
      this is relevant to the outcome of infection.

PMID- 16085919
TI  - Patterns of CD8 T-cell epitopes within the human papillomavirus type 16 (HPV 16)
      E6 protein among young women whose HPV 16 infection has become undetectable.
AB  - The patterns of CD8 T-cell epitopes recognized within the E6 protein in women who
      had cleared their human papillomavirus 16 infection were examined. T-cell lines
      were established using autologous dendritic cells infected with a recombinant
      vaccinia virus. Evidence of potential antigenic epitopes was shown in 8 of 23
      (34.8%) women.

PMID- 16085920
TI  - Comparison of Microcapillary Cytometry Technology and Flow Cytometry for CD4+ and
      CD8+ T-Cell Estimation.
AB  - An alternative technology for the estimation of T cells based on a microcapillary
      technique (Guava Technologies, Hayward, CA) was compared to FACSCount (Becton
      Dickinson, San Jose, CA). Samples from 51 human immunodeficiency virus-infected
      and 21 healthy individuals were tested. The correlation (r) of the two systems
      for CD4(+) T cells was 0.994, and the coefficient of variation was 6.5%,
      establishing equable performance between the two technologies.

PMID- 16085921
TI  - Evaluation of three influenza A and B rapid antigen detection kits--update.

PMID- 16085922
TI  - National billing codes announced for pharmacists' clinical services.

PMID- 16085923
TI  - Pharmacy clinic offers glimpse into future Medicare service.

PMID- 16085924
TI  - Medicare Part D creates challenges for safety-net providers and law enforcement.

PMID- 16085925
TI  - Money matters in infection control policy.

PMID- 16085926
TI  - Increasing medication access for the uninsured and underinsured.

PMID- 16085927
TI  - Continuity of care: a basis for professional unity in pharmacy.

PMID- 16085928
TI  - Searching for excellence in leadership transformation.

PMID- 16085929
TI  - Treatment of electrolyte disorders in adult patients in the intensive care unit.
AB  - PURPOSE: The treatment of electrolyte disorders in adult patients in the
      intensive care unit (ICU), including guidelines for correcting specific
      electrolyte disorders, is reviewed. SUMMARY: Electrolytes are involved in many
      metabolic and homeostatic functions. Electrolyte disorders are common in adult
      patients in the ICU and have been associated with increased morbidity and
      mortality, as has the improper treatment of electrolyte disorders. A limited
      number of prospective, randomized, controlled studies have been conducted
      evaluating the optimal treatment of electrolyte disorders. Recommendations for
      treatment of electrolyte disorders in adult patients in the ICU are provided
      based on these studies, as well as case reports, expert opinion, and clinical
      experience. The etiologies of and treatments for hyponatremia hypotonic and
      hypernatremia (hypovolemic, isovolemic, and hypervolemic), hypokalemia and
      hyperkalemia, hypophosphatemia and hyperphosphatemia, hypocalcemia and
      hypercalcemia, and hypomagnesemia and hypermagnesemia are discussed, and
      equations for determining the proper dosages for adult patients in the ICU are
      provided. Treatment is often empirical, based on published literature, expert
      recommendations, and the patient's response to the initial treatment. Actual
      electrolyte correction requires individual adjustment based on the patient's
      clinical condition and response to therapy. Clinicians should be knowledgeable
      about electrolyte homeostasis and the underlying pathophysiology of electrolyte
      disorders in order to provide the optimal therapy to patients. CONCLUSION:
      Treatment of electrolyte disorders is often empirical, based on published
      literature, expert opinion and recommendations, and patient's response to the
      initial treatment. Clinicians should be knowledgeable about electrolyte
      homeostasis and the underlying pathophysiology of electrolyte disorders to
      provide optimal therapy for patients.

PMID- 16085930
TI  - Use of specific indicators to detect warfarin-related adverse events.
AB  - PURPOSE: The use of specific indicators, or "triggers," to identify adverse drug
      events (ADEs) associated with warfarin therapy is described. SUMMARY: Automated
      triggers provided by laboratory and pharmacy data were used to identify potential
      ADEs associated with warfarin therapy among patients treated in the emergency
      room or admitted to six community hospitals between July 2002 and December 2003.
      The triggers consisted of an International Normalized Ratio (INR) of greater than
      3.0 and pharmacy orders for vitamin K. Pharmacists reviewed the triggers monthly
      for clinical determination of ADEs during preintervention and postintervention
      periods. Interventions consisted of staff education and real-time adjustments in
      therapy. A 39% overall reduction in ADEs occurred between the preintervention and
      postintervention periods. Harmful ADEs declined by 70%. CONCLUSION: INRs of
      greater than 3.0 and vitamin K administration appeared to be reliable indicators
      of warfarin-associated ADEs, and detection with these indicators appeared to
      reduce ADEs when combined with appropriate interventions.

PMID- 16085931
TI  - Guggulipid use in hyperlipidemia: case report and review of the literature.

PMID- 16085932
TI  - A novel, evolutionarily conserved protein phosphatase complex involved in
      cisplatin sensitivity.
AB  - Using a combination of tandem affinity purification tagging and mass
      spectrometry, we characterized a novel, evolutionarily conserved protein
      phosphatase 4 (PP4)-containing complex (PP4cs, protein phosphatase 4, cisplatin
      sensitive complex) that plays a critical role in the eukaryotic DNA damage
      response. PP4cs is comprised of the catalytic subunit PP4C; a known regulatory
      subunit, PP4R2; and a novel protein that we termed PP4R3. The Saccharomyces
      cerevisiae PP4R3 ortholog Psy2 was identified previously in a screen for
      sensitivity to the DNA-damaging agent and anticancer drug cisplatin. We
      demonstrated that deletion of any of the PP4cs complex orthologs in S. cerevisiae
      elicited cisplatin hypersensitivity. Furthermore human PP4R3 complemented the
      yeast psy2 deletion, and Drosophila melanogaster lacking functional PP4R3 (flfl)
      exhibited cisplatin hypersensitivity, suggesting a highly conserved role for
      PP4cs in DNA damage repair. Finally we found that PP4R3 may target PP4cs to the
      DNA damage repair machinery at least in part via an interaction with Rad53
      (CHK2).

PMID- 16085933
TI  - The essential light chain N-terminal extension alters force and fiber kinetics in
      mouse cardiac muscle.
AB  - The functional significance of the actin-binding region at the N terminus of the
      cardiac myosin essential light chain (ELC) remains elusive. In a previous
      experiment, the endogenous ventricular ELC was replaced with a protein containing
      a 10-amino acid deletion at positions 5-14 (ELC1vDelta5-14, referred to as
      1vDelta5-14), a region that interacts with actin. 1vDelta5-14 mice showed no
      discernable mutant phenotype in skinned ventricular strips. However, because the
      myofilament lattice swells upon skinning, the mutant phenotype may have been
      concealed by the inability of the ELC to reach the actin-binding site. Using the
      same mouse model, we repeated earlier measurements and performed additional
      experiments on skinned strips osmotically compressed to the intact lattice
      spacing as determined by x-ray diffraction. 1vDelta5-14 mice exhibited decreased
      maximum isometric tension without a change in calcium sensitivity. The decreased
      force was most evident in 5-6-month-old mice compared with 13-15-month-old mice
      and may account for the greater ventricular wall thickness in young 1vDelta5-14
      mice compared with age-matched controls. No differences were observed in unloaded
      shortening velocity at maximum calcium activation. However, 1vDelta5-14 mice
      exhibited a significant difference in the frequency at which minimum complex
      modulus amplitude occurred, indicating a change in cross-bridge kinetics. We
      hypothesize that the ELC N-terminal extension interaction with actin inhibits the
      reversal of the power stroke, thereby increasing isometric force. Our results
      strongly suggest that an interaction between residues 5-14 of the ELC N terminus
      and the C-terminal residues of actin enhances cardiac performance.

PMID- 16085934
TI  - Redefining the role of the endogenous XAP2 and C-terminal hsp70-interacting
      protein on the endogenous Ah receptors expressed in mouse and rat cell lines.
AB  - Studies using transient expression systems have implicated the XAP2 protein in
      the control of aryl hydrocarbon receptor (AHR) stability and subcellular
      location. Thus, studies were performed in cell lines that expressed endogenous
      rat or mouse Ah(b-1) (C57BL/6) or Ah(b-2) (C3H) AHRs with similar levels of
      endogenous XAP2. Unliganded rat and mouse Ah(b-2) receptor complexes associated
      with reduced levels of XAP2 and exhibited dynamic nucleocytoplasmic shuttling in
      comparison with Ah(b-1) receptors. Rat and mouse Ah(b-2) receptors also exhibited
      a greater magnitude of ligand-induced degradation than Ah(b-1) receptors. Small
      interfering RNA reduction of endogenous XAP2 by >80% had minimal impact on the
      level of Ah(b-2) receptors but resulted in a 25-30% reduction of Ah(b-1)
      receptors. XAP2 reduction resulted in increased susceptibility of the Ah(b-1)
      receptor to ligand-induced degradation yet produced higher levels of endogenous
      CYP1A1 induction. Stable expression of the Ah(b-2) receptor in the C57BL/6
      background resulted in a protein with reduced association with XAP2, dynamic
      nucleocytoplasmic shuttling, and increased levels of ligand-induced degradation.
      Small interfering RNA reduction of endogenous XAP2 in a C-terminal hsp70
      interacting protein knockout mouse cell line, exhibited a 25-30% reduction in the
      level of endogenous Ah(b-1) AHR and showed high levels of ligand-induced
      degradation. Thus, endogenous XAP2 exerts a negative function on a small fraction
      of the endogenous Ah(b-1) receptor complex but appears to have a minimal impact
      on endogenous rat or Ah(b-2) receptors. This implies that the analysis of the AHR
      mediated signaling via rat and mouse Ah(b-2) receptors may better represent the
      physiology of this signal transduction pathway.

PMID- 16085936
TI  - A PIN1 family gene, OsPIN1, involved in auxin-dependent adventitious root
      emergence and tillering in rice.
AB  - Auxin transport affects a variety of important growth and developmental processes
      in plants, including the regulation of shoot and root branching. The asymmetrical
      localization of auxin influx and efflux carriers within the plasma membrane
      establishes the auxin gradient and facilitates its transport. REH1, a rice EIR1
      (Arabidopsis ethylene insensitive root 1)-like gene, is a putative auxin efflux
      carrier. Phylogenetic analysis of 32 members of the PIN family, taken from across
      different species, showed that in terms of evolutionary relationship, OsPIN1 is
      closer to the PIN1 family than to the PIN2 family. It is, therefore, renamed as
      OsPIN1 in this study. OsPIN1 was expressed in the vascular tissues and root
      primordial in a manner similar to AtPIN1. Adventitious root emergence and
      development were significantly inhibited in the OsPIN1 RNA interference (RNAi)
      transgenic plants, which was similar to the phenotype of NPA (N-1
      naphthylphalamic acid, an auxin-transport inhibitor)-treated wild-type plants.
      alpha-naphthylacetic acid (alpha-NAA) treatment was able to rescue the mutated
      phenotypes occurring in the RNAi plants. Overexpression or suppression of the
      OsPIN1 expression through a transgenic approach resulted in changes of tiller
      numbers and shoot/root ratio. Taken together, these data suggest that OsPIN1
      plays an important role in auxin-dependent adventitious root emergence and
      tillering.

PMID- 16085935
TI  - Structural and mutational analyses of the molecular interactions between the
      catalytic domain of factor XIa and the Kunitz protease inhibitor domain of
      protease nexin 2.
AB  - Factor XIa (FXIa) is a serine protease important for initiating the intrinsic
      pathway of blood coagulation. Protease nexin 2 (PN2) is a Kunitz-type protease
      inhibitor secreted by activated platelets and a physiologically important
      inhibitor of FXIa. Inhibition of FXIa by PN2 requires interactions between the
      two proteins that are confined to the catalytic domain of the enzyme and the
      Kunitz protease inhibitor (KPI) domain of PN2. Recombinant PN2KPI and a mutant
      form of the FXI catalytic domain (FXIac) were expressed in yeast, purified to
      homogeneity, co-crystallized, and the structure of the complex was solved at 2.6
      angstroms (Protein Data Bank code 1ZJD). In this complex, PN2KPI has a
      characteristic, disulfide-stabilized double loop structure that fits into the
      FXIac active site. To determine the contributions of residues within PN2KPI to
      its inhibitory activity, selected point mutations in PN2KPI loop 1 11TGPCRAMISR20
      and loop 2 34FYGGC38 were tested for their ability to inhibit FXIa. The P1 site
      mutation R15A completely abolished its ability to inhibit FXIa. IC50 values for
      the wild type protein and the remaining mutants were as follows: PN2KPI WT, 1.28
      nM; P13A, 5.92 nM; M17A, 1.62 nM; S19A, 1.86 nM; R20A, 5.67 nM; F34A, 9.85 nM.
      The IC50 values for the M17A and S19A mutants were not significantly different
      from those obtained with wild type PN2KPI. These functional studies and activated
      partial thromboplastin time analysis validate predictions made from the PN2KPI
      FXIac co-crystal structure and implicate PN2KPI residues, in descending order of
      importance, Arg15, Phe34, Pro13, and Arg20 in FXIa inhibition by PN2KPI.

PMID- 16085937
TI  - Bronchial CD8 cell infiltrate and lung function decline in asthma.
AB  - RATIONALE: Patients with asthma have an accelerated decline in lung function,
      which can lead to irreversible airway obstruction. It is generally assumed that
      this is related to specific aspects of airway inflammation and/or remodeling.
      OBJECTIVE: We investigated the prognostic significance of bronchial eosinophil
      and CD8+ cell counts and subepithelial reticular layer thickness for the
      subsequent decline in lung function in patients with asthma after 7.5 years of
      follow-up. METHODS: In a prospective study, pre- and post-bronchodilator lung
      function (FEV1) was measured at baseline, and after 2 years and 7.5 years in 32
      patients with asthma. Annual decline in lung function after 7.5 years of follow
      up was related to type and severity of airway inflammation and remodeling in
      bronchial biopsies, which were taken at baseline and at Year 2. RESULTS: Annual
      decline in post-bronchodilator FEV1 (mean [SD], 46.6 [53.4] ml/year) was
      significantly larger than the decline in prebronchodilator FEV1 (mean [SD], 27.5
      [62.5] ml/year), indicating loss in reversibility. Although annual fall in post
      bronchodilator FEV1 was not related to thickness of the reticular layer or to
      eosinophil counts in bronchial biopsies, there was a significant correlation with
      CD8+ T cells (r=-0.39, p=0.032). Analyzing the biopsies taken at Year 2, the
      significant association between annual fall in post-bronchodilator FEV1 and CD8
      cells could independently be confirmed (r=-0.39, p=0.036). CONCLUSION: The
      outcome of asthma, as determined by the annual decline in FEV1, can be predicted
      by the bronchial CD8+ cell infiltrate. This suggests that the inflammatory
      phenotype in asthma has prognostic relevance, which may require phenotype
      specific therapeutic strategies.

PMID- 16085938
TI  - Geriatric failure to thrive.

PMID- 16085939
TI  - Prevalence of malnutrition and risk factors in geriatric patients of a
      convalescent and rehabilitation hospital.
AB  - OBJECTIVES: To investigate the prevalence and risk factors of malnutrition in
      geriatric patients admitted to a convalescent and rehabilitation hospital.
      DESIGN: Cross-sectional study. SETTING: Regional hospital, Hong Kong. PATIENTS: A
      total of 120 patients (aged 60 years or older) referred to Tung Wah Eastern
      Hospital. MAIN OUTCOME MEASURES: Anthropometric, biochemical, and haematological
      parameters were measured for nutritional assessment. Malnutrition was defined as
      a body mass index of lower than 18.5 kg/m(2) and serum albumin level of lower
      than 35 g/L. The clinical outcomes of patients were also recorded. The predictive
      value of the Chinese Mini Nutritional Assessment as a nutritional screening tool
      was assessed. Potential risk factors associated with malnutrition were evaluated
      according to established protocols. RESULTS: The mean age of patients was 80.3
      years (standard deviation, 7.4 years), and the mean body mass index was 21.9
      kg/m(2) (standard deviation, 4.4 kg/m(2)). The prevalence of malnutrition was
      16.7%. The age distribution of malnourished patients (mean, 86.2 years; standard
      deviation, 7.0 years; n=20) was significantly different to those nourished (mean,
      79.1 years; standard deviation, 6.9 years; n=100) [P=0.0001]. Mortality was also
      higher in malnourished patients (25%) than nourished patients (4%) [P=0.001].
      Based on the Chinese Mini Nutritional Assessment, 16.9% of patients were
      classified as malnourished (cut-off value, 18.5). The Chinese Mini Nutritional
      Assessment was useful as a screening tool to exclude patients who were not
      malnourished, ie it had a high negative predictive value (95%). Being totally
      dependent for the performance of activities of daily living, living in a home for
      the elderly, and being chair- or bed-bound posed a significantly increased risk
      of malnutrition. The presence of mental depression (geriatric depression scale
      score of 8 or higher), moderately or severely impaired cognitive function
      (abbreviated mental test score of lower than 7), or polypharmacy (five
      medications or more) did not significantly affect risk of malnutrition.
      CONCLUSIONS: Malnutrition was common in the geriatric patients studied and was
      associated with an increased mortality. The Chinese Mini Nutritional Assessment
      was a useful screening tool to exclude malnutrition. Significant risk factors of
      malnutrition were total dependence, living in a home for the elderly, and being
      chair- or bed-bound.

PMID- 16085940
TI  - Chromosomal abnormalities and FMR1 gene premutation in Chinese women with
      premature menopause.
AB  - OBJECTIVE: To study the prevalence of chromosomal abnormalities and FMR1 gene
      premutation in Chinese women with premature menopause in Hong Kong. DESIGN:
      Retrospective study. SETTING: Clinical Genetic Service, Hong Kong. PARTICIPANTS:
      Chinese women with premature menopause referred for cytogenetic study from
      January 1983 to November 2003. MAIN OUTCOME MEASURES: Chromosomal abnormalities,
      FMR1 gene premutation. RESULTS: Chromosomal abnormalities were present in 15.6%
      of Chinese women who suffered premature menopause. X-chromosome abnormality was
      involved in over 80% of cases. FMR1 gene premutation was present in 0.86% of 116
      cases screened for this abnormality. The predominance of X-chromosome abnormality
      accounted for the shorter stature, younger menopausal age, and higher prevalence
      of dysmorphic features among the cytogenetically abnormal patients. However, on
      logistic regression, no clinical feature was significantly correlated with
      cytogenetic abnormality. CONCLUSIONS: The prevalence of chromosomal abnormalities
      among Hong Kong Chinese women who suffer premature menopause was comparable with
      that of Caucasian and Chinese populations elsewhere. Because clinical features
      are poor predictors of cytogenetic abnormality, a pragmatic approach to screening
      is advocated. The carrier rate of fragile X premutation in these women appeared
      lower than that of Caucasians. Nevertheless, a search for FMR1 gene premutation,
      in addition to conventional chromosomal study, has important implication for
      prenatal diagnosis and fertility management for the extended family.

PMID- 16085941
TI  - Medullary thyroid carcinoma in Hong Kong Chinese patients.
AB  - OBJECTIVE: To study the clinical parameters and treatment outcome of medullary
      thyroid carcinoma in Hong Kong Chinese patients. DESIGN: Retrospective study.
      SETTING: Regional oncology unit, Hong Kong. PATIENTS: Patients with medullary
      thyroid carcinoma who were identified among 1656 patients with thyroid
      malignancies seen in a single institute in Hong Kong from January 1960 to June
      2003. MAIN OUTCOME MEASURES: Ten-year cause-specific survival, locoregional
      failure-free survival, and distant metastasis failure-free survival. RESULTS:
      Twenty-two (1.3%) patients with medullary thyroid carcinoma were identified. The
      mean age at diagnosis was 43.7 (standard deviation, 16.5) years. The sex ratio
      was 1:1. The 10-year cause-specific survival, locoregional failure-free survival,
      and distant metastasis failure-free survival were 75.4%, 82.0%, and 62.4%,
      respectively. Lymph node metastasis was present in seven (31.8%) patients at
      diagnosis. Distant metastasis developed in nine (40.9%) patients: lung, 3
      (13.6%); bone, 5 (22.7%); liver, 2 (9.1%); mediastinum, 4 (18.2%). Seven (31.8%)
      patients died of distant metastasis. Mediastinal (n=3) and bone metastases (n=3)
      were important causes of death. Genetic study confirmed multiple endocrine
      neoplasia type 2A in 3 (25.0%) of 12 patients who all had bilateral and
      multifocal diseases. Younger age (<45 years) was associated with better survival,
      better locoregional control, and less distant metastasis. Patients with pT1N0
      disease (n=3) had an excellent prognosis: all were disease-free following total
      thyroidectomy. Among eight patients who received external radiation therapy,
      seven achieved good locoregional control. In seven patients with lymph node
      metastasis, external radiation therapy gave 100% (4/4) locoregional control
      compared with 33.3% (1/3) in those without external radiation therapy.
      Chemotherapy using dacarbazine and 5-fluorouracil was tried in three patients
      with poor response. CONCLUSIONS: Early stage (T1N0) medullary thyroid carcinoma
      is associated with a very good prognosis. Postoperative external radiation
      therapy can achieve good locoregional control in patients with lymph node
      metastasis or locally advanced disease.

PMID- 16085942
TI  - Idiopathic macular hole surgery in Chinese patients: a randomised study to
      compare indocyanine green-assisted internal limiting membrane peeling with no
      internal limiting membrane peeling.
AB  - OBJECTIVE: To compare the anatomical and visual outcomes of primary idiopathic
      macular hole surgery using indocyanine green-assisted internal limiting membrane
      peeling versus no internal limiting membrane peeling. DESIGN: Prospective
      randomised controlled clinical trial. SETTING: University teaching hospital, Hong
      Kong. PATIENTS: Fifty-one eyes of 49 Chinese patients with primary idiopathic
      macular hole were studied. INTERVENTIONS: Patients were randomised to undergo
      pars plana vitrectomy with indocyanine green-assisted internal limiting membrane
      peeling (26 eyes) or surgery without internal limiting membrane peeling (25
      eyes). Perfluorocarbon gas was used in all cases as internal tamponade. MAIN
      OUTCOME MEASURES: Primary macular hole closure rate and best-corrected visual
      acuity. RESULTS: The mean follow-up duration was 12 months (range, 6-23 months).
      Respectively to the indocyanine green-assisted internal limiting membrane peeling
      group and non-internal limiting membrane peeling group, the primary anatomical
      closure rate was 92.3% and 32.0% (P<0.001), whereas improvement in best-corrected
      visual acuity was 3.7 and 1.5 lines (P=0.002). More eyes in the first group
      (84.6%) had improvement of 2 or more lines of best-corrected visual acuity after
      surgery than in the second group (32.0%) [P<0.001]. Multivariate logistic
      regression showed indocyanine green-assisted internal limiting membrane peeling
      was the only significant predictor for primary closure of the macular hole
      (adjusted odds ratio=30.8). CONCLUSION: Indocyanine green-assisted internal
      limiting membrane peeling in idiopathic macular hole surgery results in
      significantly better anatomical and visual outcomes compared with non-internal
      limiting membrane peeling in Chinese patients.

PMID- 16085943
TI  - Cytogenetic analysis of patients with primary and secondary amenorrhoea in Hong
      Kong: retrospective study.
AB  - OBJECTIVE: To estimate the incidence and type of chromosomal abnormalities in
      patients with primary and secondary amenorrhoea in Hong Kong. DESIGN: Cytogenetic
      analysis and retrospective review. SETTING: Clinical Genetic Service, Department
      of Health, Hong Kong. PATIENTS: Case records of 549 patients with either primary
      (n=237) or secondary (n=312) amenorrhoea referred to the Clinical Genetic Service
      from 1 January 1991 to 30 April 2002 were reviewed. All these patients with
      amenorrhoea would have karyotyping (G banding) performed. MAIN OUTCOME MEASURES:
      Clinical characteristics of patients, and incidence and type of chromosomal
      abnormalities in the local population. RESULTS: Sex chromosome anomaly was found
      in 24.5% and 9.9%, respectively, of women with primary and secondary amenorrhoea.
      In those with primary amenorrhoea, male karyotype was identified in 8.4% and X
      chromosome abnormalities in 16.0%. CONCLUSION: The incidence of chromosomal
      abnormalities in women with amenorrhoea is similar to that reported in the
      literature. Chromosomal abnormalities are identified often enough to warrant
      karyotyping of all women with amenorrhoea.

PMID- 16085944
TI  - Primary care of patients with sexually transmitted diseases or genitourinary
      symptoms in Hong Kong.
AB  - OBJECTIVES: To determine the adequacy of care received from general practitioners
      by patients with sexually transmitted diseases or genitourinary symptoms. DESIGN:
      Prospective study. SETTING: Hong Kong. PARTICIPANTS: Diagnoses and drug data
      obtained from logbooks submitted by doctors studying for the Diploma in Family
      Medicine and candidates for Fellowship examinations between 1999 and 2002. MAIN
      OUTCOME MEASURES: Diagnosis or symptom of a sexually transmitted disease and
      prescribed treatment. RESULTS: Sexually transmitted diseases and genitourinary
      symptoms accounted for 1.1% of the workload of these community doctors in Hong
      Kong. The majority of patients were young adult males. The overall standard of
      treatment was inadequate: both multi-pharmacy and inappropriate treatment was
      common; in up to 30% of cases, doctors ignored local or international guidelines.
      CONCLUSION: Primary care doctors play an important role in the diagnosis and
      management of sexually transmitted diseases or genitourinary symptoms in Hong
      Kong. A high index of suspicion should be maintained and continuing education
      made available if doctors are to provide an equally high standard of care.

PMID- 16085945
TI  - Genetic markers for retinitis pigmentosa.
AB  - OBJECTIVE: To review recent advances in the molecular genetics of retinitis
      pigmentosa with emphasis on the development of genetic markers that aids
      diagnosis and prognosis. DATA SOURCES AND EXTRACTION: Literature search of
      MEDLINE from 1988 to 2005 using the following key words: 'retinitis pigmentosa',
      'rhodopsin', 'RP1', 'RPGR', and 'genetic counseling'. References of two genes-
      RHO and RP1--causing retinitis pigmentosa in the Chinese population were
      reviewed. STUDY SELECTION: Literature and data related to genetic markers for
      retinitis pigmentosa. DATA SYNTHESIS: The genetics of retinitis pigmentosa is
      complex. It can be sporadic or familial, with heterogeneous transmission modes.
      Retinitis pigmentosa is associated with nearly 40 chromosomal loci, where 32
      candidate genes have been identified. A large number of mutations are known to
      cause retinitis pigmentosa. But no single mutation alone accounts for more than
      10% of unrelated retinitis pigmentosa patients. Genetic tests for retinitis
      pigmentosa require screening for a consort of mutations in a large number of
      genes. High throughput screening technology such as denaturing high performance
      liquid chromatography and automated DNA sequencing should make such tests
      feasible. CONCLUSIONS: Rapid developments in the understanding of the genetics of
      retinitis pigmentosa have helped to establish genetic tests of clinical value.
      The complex mode of inheritance nonetheless makes genetic counselling difficult,
      even in the presence of positive genetic screening results.

PMID- 16085946
TI  - Induced sputum in childhood asthma.
AB  - Asthma is characterised by variable degrees of airway obstruction, airway hyper
      responsiveness, and chronic airway inflammation. Current guidelines emphasise
      that inhaled corticosteroid treatment is the mainstay of asthma therapy because
      it targets the underlying airway inflammation. It is prudent to use the lowest
      possible dose of inhaled corticosteroid compatible with good asthma control. In
      clinical practice, the use of or the reduction of inhaled corticosteroid dosage
      is based on symptoms and lung function, both of which have been shown to have a
      poor correlation with airway inflammation. The use of induced sputum as a marker
      of airway inflammation improves asthma monitoring and optimises treatment in
      adults. This review discusses the technique of sputum induction, its clinical
      application, and our experience of its use in asthmatic children.

PMID- 16085947
TI  - Recurrent variceal bleeding in a young woman.
AB  - Congenital hepatic fibrosis is an uncommon fibrocystic disorder affecting the
      intrahepatic bile ducts. It has autosomal recessive inheritance. The main
      consequence of this condition is portal hypertension and it is often misdiagnosed
      as cirrhosis. Patients with congenital hepatic fibrosis usually present during
      childhood or early adolescence with oesophageal variceal bleeding. Portosystemic
      shunt surgery is the treatment of choice for these patients as the risk of
      postoperative hepatic encephalopathy is low. We report a patient with congenital
      hepatic fibrosis who presented with oesophageal variceal bleeding at the age of
      16 years, initially misdiagnosed as having cryptogenic liver cirrhosis. The
      patient experienced two further episodes of oesophageal variceal bleeding in
      subsequent years. She eventually underwent portosystemic shunt surgery. One year
      after the operation, the shunt remained patent on Doppler ultrasonography, and
      there had been no further episodes of variceal bleeding post-surgery.

PMID- 16085948
TI  - Partial rhombencephalosynapsis and Chiari II malformation.
AB  - We report a rare case of partial rhombencephalosynapsis coexistent with Chiari II
      malformation in a 6-year-old girl and discuss the features of these entities on
      magnetic resonance imaging.

PMID- 16085949
TI  - Benign metastasising leiomyoma: a rare but possible cause of bilateral pulmonary
      nodules in Chinese patients.
AB  - We report three cases of benign metastasising leiomyoma, which is a rare cause of
      multiple lung nodules, in three Hong Kong Chinese females. One patient presented
      with pleuritic chest pain, another was asymptomatic, while the last presented
      with haemoptysis. All three patients had previously undergone surgical resection
      of uterine leiomyomas. Multiple lung nodules mimicking lung metastases were
      demonstrated on chest radiographs, and all three diagnoses were obtained from
      lung biopsies. Hormonal therapy was given to two patients with variable
      responses. To the best of our knowledge, this is the first report of benign
      metastasising leiomyoma in Hong Kong Chinese population. It highlights the
      importance of considering this rare and benign disease in premenopausal females
      presenting with multiple lung nodules.

PMID- 16085950
TI  - Necrotic cardiac haemangioma masquerading as sepsis with disseminated
      intravascular coagulation.
AB  - Cardiac haemangiomas are exceptionally rare benign vascular tumours. We report a
      case of cardiac haemangioma presenting with pyrexia of unknown origin and
      clinical features simulating sepsis with disseminated intravascular coagulation.
      The clinical course was complicated by systemic embolism.

PMID- 16085951
TI  - Jehovah's Witnesses and surgery.

PMID- 16085952
TI  - Use of Pediatric Index of Mortality (PIM) and the Pediatric Risk of Mortality
      (PRISM) III-24 for prediction of mortality.

PMID- 16085954
TI  - Legal recognition of advance refusal.

PMID- 16085955
TI  - [The significance of cardiac symptoms in patients referred to pediatric
      cardiology outpatient clinics].
AB  - OBJECTIVE: To determine the significance of cardiac symptoms in patients referred
      to paediatric cardiology outpatient clinics. MATERIAL AND METHODS: All patients
      above l month of age referred to paediatric cardiac outpatient clinics between 01
      Apr-2004 and 31-Dec-2004. Data was collected prospectively in Internet data base.
      Patients were divided into 3 groups: patients referred by paediatricians to
      regional paediatric cardiology outpatient clinic (group 1, N=3383), patients
      referred to Academic Paediatric Cardiac outpatient clinics by paediatricians
      (group 2, N= 7461) and by cardiologists (group 2a, N=793). RESULTS: Average age
      of patients was 6.4 +/- 5.8 years. The most common reasons for referral included
      cardiac murmur, chest pain, syncope, earlier diagnosed congenital heart disease
      (CHD). The proportion of patients referred by cardiologists and paediatricians
      because of murmur was 30% vs 56%, arrhythmia 12.6% vs 8% and CHD 44% vs 8%. The
      percentage of the significant cardiac pathology in all groups (l/ 2/ 2a) was
      38/35/76; in patients with chest pain -- 9/18/0; with syncope -- 56/70/80; with
      murmur -- 19/21/43; with CHD -- 68/69/93 and with arrhythmia -- 57/80/92.
      CONCLUSIONS: l. There were no significant differences between patients referred
      by paediatricians from regional and academic outpatient cardiology clinics. 2.
      Isolated cardiac symptoms such as chest pain, cardiac murmur and syncope were
      caused by significant cardiac pathology only in about 1/5 cases. 3. Cardiac
      murmur was the most common reason for referral to cardiac outpatient clinic in
      younger patients, in older group syncope and arrhythmia were more frequent.

PMID- 16085956
TI  - [Assessment of cardiac function in fetuses with intrauterine growth retardation
      using the Tei Index].
AB  - The aim of the study was to evaluate cardiac function in foetuses with IUGR,
      using the Tei Index. MATERIAL AND METHODS: Prenatal echocardiographic examination
      was performed in 64 foetuses with intrauterine growth retardation between 25-27,
      30-32, and 34-37 weeks of gestation. The control group included 30 healthy
      foetuses. Flow velocity waveforms of mitral and tricuspid valve and flow velocity
      waveforms of the aortic and pulmonic valves were obtained. The Tei Index for left
      and right ventricle was calculated. The heart rate was measured in all foetuses.
      RESULTS: The Tei Index for left ventricle in foetuses with intrauterine growth
      retardation was significantly higher than in healthy foetuses (25-27 hbd - 0.6
      vs. 0.58; p<0.05: 30-32 hbd -0.59 vs. 0.52; p<0.05: 34-36 hbd - 0.58 vs. 0.48;
      p<0.001). The Tei Index for right ventricle was also significantly higher in
      foetuses with intrauterine growth retardation than in the control group. The Tei
      Index decreased gradually with advancing gestational age and is independent of
      heart rate. CONCLUSIONS: l. Foetuses with intrauterine growth retardation have
      abnormal cardiac function in later part of gestation. 2. The Tei Index may be
      applied to evaluate cardiac function in foetuses.

PMID- 16085957
TI  - [Early one-stage repair of tetralogy of Fallot].
AB  - OBJECTIVE: To evaluate the outcome after early, primary repair of Tetralogy of
      Fallot (TOF) in children under 6 months of age. METHODS: 74 infants, who
      underwent repair of TOF between 1992 and 2003, aged from 1.5 to 6 months, were
      investigated. 32 (43%) patients were cyanotic, 14 (18%) had anoxemic spells. Most
      of them were qualified for surgical procedure by echocardiographic study only, 26
      patients required cardiac catheterisation. Two had balloon angioplasty prior to
      primary repair. None of them underwent initial palliation. Mean follow-up was 4.9
      years (1 -9.5 years). RESULTS: 71 children survived and they were in good
      condition. 3 patients died (mortality 3.6%). One child required reoperation.
      Transannular patch (TAP) was inserted in 66% of patients. Right ventricular
      outflow tract obstruction (RVOTO) more than 40 mmHg occurred in 2 infants.
      Moderate pulmonary insufficiency was present in 38 infants (25%). None of the
      patients had QRS complex longer than 140 msec. CONCLUSIONS: Early one-stage
      repair of TOF was achieved with low mortality rate and low risk for reoperation
      (1.5%). It eliminates initial palliation and drug therapy.

PMID- 16085958
TI  - [Comparison of lipid and lipoprotein(a) metabolism in blood serum and the
      thickness of common carotid artery (intima-media thickness complex-- IMT), in
      children from families at risk for cardiovascular disease and in families without
      risk].
AB  - THE AIM: The aim of the study was to compare selected parameters of lipid and
      lipoprotein metabolism in blood serum and the thickness of common carotid artery
      wall (intima-media thickness complex -- IMT) in children from families at risk
      for circulatory system disease in their history and in families without this
      risk. MATERIAL AND METHODS: The study included 18 children aged 2-3 years from
      families with circulatory system disease in their history. The control group was
      composed of 16 children aged 2-3 years from families without that risk. In all of
      the subjects concentrations of triglycerides, total cholesterol and its
      fractions: LDL, VLDL, HDL and of lipoprotein(a) in blood serum were determined.
      The intima-media thickness (IMT) measurement in children was made with
      ultrasonographic method. RESULTS: The concentration of triglycerides, VLDL
      cholesterol and lipoprotein(a) had the highest value in the blood serum of the
      children from the families with circulatory system disease in their history as
      compared to the levels of the children from families without that risk and the
      differences were statistically significant (p<0.05). The mean values of IMT in
      children from families with positive history were higher than in children in the
      control group, but these differences were not statistically significant.
      CONCLUSIONS: The appearance of lipid metabolism disorders and higher lipoprotein
      concentration in children from families with circulatory system disease in their
      history allows us to conclude that the children from those families constitute a
      high risk group. Lipid profile should be periodically controlled in those
      children. Moreover, in justifiable cases atherosclerosis changes indexes should
      be controlled as well. However; IMT examination of the carotid artery, as a non
      invasion method, can be a very useful method in tracing the early development of
      atherosclerosis changes in children's vessels, especially in children from
      families with circulatory system disease in their history.

PMID- 16085959
TI  - [Kawasaki disease in children--9 years experience].
AB  - PURPOSE: The aim of the study was assessment of the course and treatment of
      Kawasaki disease on the basis of own experience. MATERIAL AND METHODS: Between
      November 1995 and December 2004 Kawasaki disease (KD) was diagnosed in 30
      patients, (20 boys, 10 girls). The median age in acute stage was 20 months (range
      1-96 months). Patients were divided into 4 groups (gr) according to changes in
      coronary arteries (CA). Group 1 (N=13) without CA aneurysms (CAA), group II (N=5)
      with small (<5mm) CAA. Group III (N=5) with medium (5-8mm) CAA, group IV (N=7)
      with giant (>8mm) CAA. Echocardiographic examination was performed in all
      patients. In echocardiographic examination the following were observed: CAA and
      valvar insufficiency in 15 patients, left ventricle enlargement in 3 patients,
      pericardial effusion in 6 patients. The treatment was intravenous immunoglobulin
      and aspirin in all patients, steroid treatment in 2 patients methylprednisolone,
      in 2 patients prednisone, in l patient hydrocortisone. The anti-inflammatory
      treatment was started after 10 days of illness in 66.7% of patients. Thrombi in
      CAA were treated in 6 patients, the treatment was: in all tissue - type
      plasminogen activator iv and intracoronary in 2 patients; heparin in all;
      enoxaparine in 3 patients; abciximab in 2 patients; acenocumarol and aspirin in
      all. Coronary angiographies were performed in 2 patients in acute stage of
      disease for thrombolytic therapy and in 4 patients during follow-up. Myocardial
      perfusion was assessed in SPECT (Single Photon Emission Computed Tomography) in 6
      patients. Two children with giant CAA died during the first 8 months of acute
      stage (6.7%), 2 patients we lost from follow-up. 26 patients are in follow-up.
      RESULTS: during anti-inflammatory treatment (immunoglobulin, aspirin, steroid
      treatment) loss of fever, normalization of inflammatory markers, and no side
      effect, were observed except for 1 patient treated with methylprednosolone with
      thrombi in CAA during treatment and no side effects during treatment. During the
      follow-up period CAA regressed in 5 patients (35.7%), CAA became smaller in 7
      patients (50%), CAA were the same in 2 patients (14.3%). Changes in
      echocardiographic examination: valvar insufficiency, left ventricle enlargement,
      pericardial effusion, disappeared during follow-up. Perfusion defects were
      observed in 4 patients in SPECT. In coronary angiography changes were observed in
      coronary arteries in 4 patients. CONCLUSIONS: 1. Kawasaki disease was diagnosed
      in 66.7% children after 10 days of illness. 2. Coronary artery aneurysms were
      found in 56.6% treated children. 3. Regression of CAA was observed in 37.5%
      patients mainly with small CAA. They became smaller in 50% cases mainly with
      medium and giant CAA. 4. Mortality rate was 6.7% and concerned children with
      giant CAA; they died during the first 8 months of illness. 5. Thrombolytic
      treatment of thrombi in CAA (rt-PA, heparin, enoxaparine, abciximab,
      acenocumarol, aspirin) was safe and successful. 6. In all patients with medium
      and giant CAA in the acute stage, changes were observed in echocardiographic,
      angiographic examination and myocardial perfusion during follow-up.

PMID- 16085960
TI  - [Clinical picture and molecular analysis in a familial case of Nail-Patella
      Syndrome--identification of a new mutation in LMX1B gene].
AB  - The Nail-Patella Syndrome (NPS) (OMIM: 161200) is an autosomal dominant disorder
      characterized by skeletal malformations, such as: patellar aplasia/ hypoplasia,
      iliac horns on X-ray as well as nail dysplasia, renal and ocular abnormalities.
      Mutations in the gene encoding transcription factor LMX1B, mapped on the long arm
      of chromosome 9 (9q34), are responsible for the clinical phenotype of NPS. A
      familial case (in the mother and her son) of Nail-Patella Syndrome is presented
      here. DNA analysis has shown a new missense mutation in exon 5 of LMX1B gene
      (745C-G) leading to a change of glutamine into glutamic acid (Q245E) in the coded
      protein. Characteristic clinical features, seen in both patients, are discussed
      within the context of molecular analysis results.

PMID- 16085961
TI  - [Superoxide dismutase in children with juvenile idiopathic arthritis].
AB  - The use or antioxidants as drugs that may control the inflammatory process
      recently has become widely studied in adults. One of the most important
      components or antioxidant barrier in humans is enzyme superoxide dismutase.
      Experimental treatment with superoxide dismutase proved to be effective in
      animals. THE AIM of the present study was to estimate the activity of superoxide
      dismutase (SOD) in patients with rheumatoid disease of childhood -- juvenile
      idiopathic arthritis and to analyse it in different clinical aspects of the
      disease including its activity, course and time of duration. MATERIAL AND
      METHODS: A group of 70 children with juvenile idiopathic arthritis, age from 3 to
      18 years, patients of Rheumatologic Hospital in Sopot was examined in years 1996
      2001. Juvenile idiopathic arthritis was diagnosed according to the International
      League Against Rheumatism classification (Durban 1997). The control group
      consisted of 29 healthy children age from 3 to 18 years. Superoxide dismutase
      activity was determined in full, heparinised blood with the use of
      spectrophotometric method or Randox. The study was accepted by the Local
      Committee of Ethics. RESULTS: A statistically significant increase in superoxide
      dismutase activity was found in group of children with juvenile idiopathic
      arthritis compared to the control group. In the polyarticular form of disease the
      activity of superoxide dismutase was also significantly higher than in the
      control group. CONCLUSIONS: In course of juvenile idiopathic arthritis,
      differently from rheumatoid arthritis of adults, superoxide dismutase activity
      seems to be stimulated in the majority of cases, so the treatment with exogenous
      superoxide dismutase may not be effective.

PMID- 16085962
TI  - [Diagnostic value of thermography and endothelin concentration in serum of
      children with Raynaud's Syndrome].
AB  - OBJECTIVE: The primary Raynaud's Syndrome may occur in pubescent children, the
      secondary is connected with connective tissue diseases. The aim of this study was
      to evaluate the diagnostic value of thermography and endothelin concentration in
      patients with Raynaud's Syndrome (RS). MATERIAL AND METHODS: 49 patients aged 11
      to 18 years with clinical symptoms of RS and 12 healthy children participated in
      the study. 17 patients had secondary and 32 primary RS. Thermography was
      conducted in all children. Vasomotor disturbances were diagnosed by Doppler
      ultrasonography. Palm temperature measurements were taken in room temperature
      before, directly after the cooling test and 4 minutes later. ET-1 serum
      concentration was tested by ELISA. RESULTS: The mean palm temperatures after the
      cooling test were significantly lower than in control group. (26.28 +/- 3.13C vs
      30.26 +/- 1.11C p<0.001). There was no difference between primary and secondary
      RS. After cooling, the palm temperatures were statistically lower than before the
      test in all children (primary RS -19.56 +/- 1.68; secondary RS -18.7 +/- 1.02;
      control group -- 18.98 +/- 0.39). The warming up speed of palm after 4 minutes
      from the cooling test was similar in investigated and control groups. There was
      no statistically significant difference in the mean concentration values of ET-1
      in sera of children with RS and the control group (1.62 +/- 0.86 pg/ml vs 1.27 +/
      0.4 pg/ml). CONCLUSIONS: 1. Thermographic estimation of palm temperatures in
      children with RS is a good diagnostic method of vasomotor disturbances. 2. Assay
      of ET-1 serum levels seem not to have significant diagnostic value.

PMID- 16085963
TI  - [The role of insulin secretion and insulin resistance in the clinical course of
      newly diagnosed diabetes mellitus in children].
AB  - BACKGROUND: The prevailing type of diabetes in Caucasian children and adolescents
      is type l. Insulin resistance resulting from decreased physical activity and
      obesity may account for the rising incidence of type l and type 2 diabetes
      mellitus in this group. AIM: To estimate the role of insulin secretion and
      insulin resistance in the clinical course of new onset type l diabetes mellitus
      in children and adolescents. MATERIALS AND METHODS: 58 patients aged 7.6-17.9
      years, underwent investigations within the first 7 days after diabetes mellitus
      diagnosis. In 56 individuals type l and in 2 - type 2, was diagnosed. Insulin
      secretion was estimated by measurement of the serum C-peptide concentration in
      glucagon test while the Euglycemic-hyperinsulinemic clamp was performed to assess
      insulin resistance. HbA1c, glycemia and pH were examined. Body mass index (BMI)
      and the required daily dose of insulin (DDI) were calculated. RESULTS: In
      patients with diabetes C-peptide level was 0.03-1.5 pmol/ml. Index M ranged from
      1.5 to 13.09 mg/kg/min. The hyperbolic relation was observed between C-peptide
      level and index M (r=0.62). There was a positive correlation between age at
      diabetes onset and C-peptide level (r=0.25) and negative with index M (r=-0.59).
      C-peptide level and index M correlated with body mass index (r=0.58; r=0.59;
      respectively). A relationship between glycemia and C-peptide level (r=-0.42) and
      index M (r=0.26) was found. Correlation between HbA1c and C-peptide level (r=
      0,42; p=0.001) and index M (r=0.3) was observed. Dose of insulin correlated with
      C-peptide level (r=-0,2). CONCLUSIONS: In children with newly diagnosed diabetes
      mellitus a great variability of insulin secretion and insulin resistance was
      observed and a hyberbolic function between them. There was a relationship between
      insulin secretion and insulin resistance with age at onset and obesity. C-peptide
      level mainly determined HbA1c, glycaemia, pH and the needed dose of insulin.

PMID- 16085964
TI  - Meningococcemia update vaccination and chemoprophylaxis.

PMID- 16085965
TI  - Predictors of fatality in neonates requiring mechanical ventilation.
AB  - OBJECTIVE: To evaluate initial arterial blood gas, pulmonary pressures, pulmonary
      mechanics (compliance and resistance), pulmonary volumes, oxygenation indices and
      serum carotenoid levels as predictors of fatality in mechanically ventilated
      neonates. DESIGN: Cross Sectional. SETTING: Referral neonatal unit of a teaching
      hospital. SUBJECTS: 83 mechanically ventilated outborn neonates. METHODS: 83
      neonates consecutively put on mechanical ventilator from March to December 2001
      were enrolled in the study. The mechanical ventilator used was pressure limited
      time cycled ventilator with facility for online measurement of volumes and
      pulmonary mechanics. Arterial blood gas after half an hour of initiation of
      mechanical ventilation and initial pulmonary pressures, pulmonary compliance,
      resistance and duration of mechanical ventilation were recorded in a pre
      structured proforma. Initial serum carotenoid levels were also measured using
      spectrophotometric method. The neonates were regularly followed up for outcome.
      Multiple logistic regression analysis was done to find out the predictors of
      fatality for those variables that were significantly associated with outcome on
      univariate analysis. RESULTS: On univariate analysis weight ( < 2000 g),
      gestational age <34 weeks, pH <7.3, duration of mechanical ventilation <72 hours,
      a/A <0.25, compliance <1 mL/cmH2O, fraction of inspired oxygen (FiO2) >60%,
      oxygenation index >10, AaDO2 >250 and serum carotenoid levels < 100 microg/dL
      were significantly associated with fatality in neonates requiring mechanical
      ventilation. However, on multiple regression analysis only FiO2, gestational age
      and serum carotenoids < 100 microg/dL were found to be independent predictors of
      fatality. CONCLUSIONS: Initial FiO2 > 60%, gestational age <34 weeks and initial
      serum carotenoid levels < 100 microg/dL were independent predictors of fatality
      in neonatal mechanical ventilation. Even in a setting with high fatality rates,
      high risk of mortality in mechanically ventilated neonates can be identified.

PMID- 16085966
TI  - Understanding and addressing childhood immunization coverage in urban slums.
AB  - The National Population Policy (2000) aims at complete protection of all children
      against vaccine preventable diseases by 2010. Urban poor, many residing in slums,
      comprise about one fourth of India's 285 million urban population. 60% of the
      children aged 12-23 months in urban India are fully immunized; coverage among
      urban poor children is a dismal 43%. The inter state variations of immunization
      coverage in urban areas, reveals a service coverage gap which calls for a rethink
      on resource allocation and strengthening processes to improve immunization
      coverage amongst urban poor. Debilitating environmental conditions and high
      population density in slums expedite disease transmission. Comparisons of urban
      rural disease incidence indicate a particular urban risk for vaccine preventable
      diseases. This paper attempts to understand the current scenario and challenges
      in improving immunization coverage in urban slums; immunization being one of the
      most successful public health interventions of the past century. It also
      discusses possible mechanisms for effectively reaching the often left out urban
      poor. Coordinated activities by the multitude of providers, accurate information
      based outreach, effective monitoring and community enablement to demand quality
      services are critical for improving utilization of immunization services by a
      heterogeneous urban poor population.

PMID- 16085967
TI  - Infections related to vascular catheters in a pediatric intensive care unit.
AB  - We determined the rate and risk factors for colonization of 103 peripheral
      intravenous catheter and 32 central venous catheters. 52.5% peripheral catheters
      had colonization. Common organisms isolated were Pseudomonas (33.3%) and
      coagulase negative Staphylococci (29.6%). Colonization was higher in catheters
      inserted in the lower limb. Overall 62.5% of the central catheters were
      colonized, chiefly by coagulase negative Staphylococci, Pseudomonas and Candida.
      All central catheters in place for more than 11 days were colonized. Subclavian
      vein catheters had a higher rate (68.2%) of colonization in comparison to femoral
      vein insertions (40%). We conclude that upper limb placements are preferable to
      lower limbs when using peripheral lines. Changing peripheral intravenous
      catheters every 48 hours and central venous catheters every 10 days may decrease
      the rate of colonization.

PMID- 16085968
TI  - Behavioral problems in children with Down syndrome.
AB  - Forty consecutive children with Down syndrome were included as the Study Group
      (SG). The Control Group (CG) consisted of forty children attending the
      immunization clinic in pediatric OPD. Behavior Screening Questionnaire (BSQ) was
      used to screen the study groups as well as their siblings and control group for
      behavioral problems. The assessment of parental attitudes was done on Attitude
      Screening Questionnaire which includes 2 separate questionnaire for mother and
      father. Twenty two children (55%) with Down's syndrome showed behavioral problems
      as compared to 5 (12.5%) in control group. Children with Down's syndrome showed
      behavioral problems related to all the spheres (feeding, socialization, toilet
      training and sleep) as compared to control group. Mothers showed highly indulgent
      attitude as related to feeding to nearly total neglect as related to
      socialization and toilet training whereas in Paternal Attitude Screening
      Questionnaire, there was total neglect in all the spheres as compared to control
      group. There is higher prevalence of psychiatric disorders in children with
      Down's syndrome and their siblings.

PMID- 16085969
TI  - Polymerase chain reaction in rapid diagnosis of neonatal sepsis.
AB  - In a prospective study a total of hundred neonates who fulfilled the American
      College of Obstetrics and Gynecology's (ACOG) criteria for probable sepsis
      admitted to NICU of tertiary care armed forces hospital were investigated for
      evidence of sepsis. The investigation protocol included sepsis screen, blood
      culture and 1 mL of venous blood for molecular analysis by polymerase chain
      reaction (PCR) for bacterial DNA component encoding 16 s RNA in all cases. 100
      newborns with probable sepsis were studied to evaluate the molecular diagnosis of
      sepsis using PCR amplification of 16 S RNA in newborns with risk factors for
      sepsis or those who have clinical evidence of sepsis. We compared the results of
      PCR with blood culture and other markers of sepsis screen (total leucocyte count
      (TLC), absolute neutrophil count (ANC), immature/total neutrophil count ratio
      (I/T ratio), peripheral blood smear, micro ESR and C reactive protein (CRP).
      Controls consisted of 30 normal healthy newborns with no overt evidence of
      sepsis. Sepsis screen was positive in 24 (24%) of cases in study group with
      sensitivity and specificity of 100% and 83.5% respectively. Blood culture was
      positive in 09(9%t) with sensitivity of 69.2% and specificity of 100%. PCR was
      positive in 13(13%) of cases (9% are both blood culture and sepsis screen
      positive and 4% are positive by sepsis screen); the sensitivity of PCR was 100%
      and specificity was 95.6%. Blood culture is the most reliable method for
      diagnosis of neonatal sepsis. Polymerase chain reaction is useful and superior to
      blood culture for early diagnosis of sepsis in neonates.

PMID- 16085970
TI  - Identification of Chlamydia trachomatis with polymerase chain reaction in middle
      ear fluid in otitis media with effusion.
AB  - In this study, 78 middle ear aspiration samples from 59 children between the ages
      of 2 14 who have undergone myringotomy under general anesthesia were included.
      The presence of DNA genome of Chlamydia trachomatis was analyzed with polymerase
      chain reaction in the aspiration material. The relationship between the nature of
      the effusion fluid and the presence of Chlamydia trachomatis was investigated. Of
      the seventy eight middle ear effusions, 26 (33.3%) were serous, 31 were (39.7%)
      mucoid and 21 (26.9%) were sero mucoid in nature. Chlamydia trachomatis DNA
      genome was identified in seven (8.9%) effusion samples. Of these, three were
      mucoid (42.8%), three were serous (42.8%) and one was sero mucoid (14.2%) in
      character. We think that during the bacteriological analyses carried out for the
      cases of otitis media with effusion, Chlamydia trachomatis should be taken into
      consideration both at the time of diagnosis and the treatment.

PMID- 16085971
TI  - Evaluation of the use of DMSA in culture positive UTI and culture negative acute
      pyelonephritis.
AB  - This prospective study was done to assess the frequency of acute pyelonephritis
      (APN) in febrile children with positive urine culture as documented by Tc99m DMSA
      scintigraphy (DMSA) and the frequency of vesicoureteric reflux (VUR) in these
      children. Secondly, to determine the frequency of APN, in febrile children with
      supportive evidence for UTI but with negative urine culture, as documented by
      DMSA and frequency of VUR in them. Thirdly to stress the utility of DMSA to
      diagnose APN in urine culture negative febrile children and to suggest DMSA as a
      clinical tool in evaluation of fever of unknown origin (FUO). This study included
      42 children with positive urine culture and 26 children with negative urine
      culture who had supportive evidence of UTI as determined by the predetermined
      criteria and diagnosed to have APN by DMSA. All of them had ultrasonogram (USG),
      DMSA and voiding cystourethrogram (VCU). They were followed up for a minimum
      period of 6 months. Out of the 42 children with positive urine culture 92.9% had
      features of APN in the DMSA of whom 82.1% had vesicoureteric relux (VUR). The
      DMSA was abnormal in 26 children with negative urine culture, of whom 65.4% had
      VUR. Ultrasound suggestive of parenchymal change was observed in 47.6% in the
      culture positive group and 65.4% in the culture negative group. In conclusion, it
      is suggested, that DMSA is a useful investigation for the diagnosis of APN in
      febrile UTI. DMSA is indicated in febrile children with negative urine culture
      but with supportive evidence of UTI and in FUO. An abnormal DMSA is a strong
      indication for work up for VUR.

PMID- 16085972
TI  - Prevalence of childhood and adolescent disabilities in rural Nepal.
AB  - The study aimed to determine the number of children and young people reported as
      having a disability by family members, and to classify impairments leading to
      disability. A Cross-sectional census was conducted of all households in 24 rural
      geopolitical units of Makwanpur district, Nepal. Heads of household were asked
      about family members under the age of 20 with disability. Such members were
      resident in 733 of 28,376 households, a household prevalence of 2.58%. 829 people
      under the age of 20 were reported as having a disability, a population prevalence
      of 0.95%. The commonest functional impairments reported were motor and the
      commonest anatomical impairments involved the limbs. More males with disability
      were identified than females.

PMID- 16085973
TI  - G 6 PD deficiency induced hemolysis in diabetic twins.
AB  - We report hemolysis due to glucose-6-phosphate dehydrogenase (G-6-PD) deficiency
      in two Egyptian monozygotic brothers, at the onset of diabetes type 1. Hemolysis
      occurred following the treatment of hyperglycemia and ketoacidosis (one twin). It
      was related to unknown G-6-PD deficiency. The fall in glucose availability after
      the treatment of hyper glycemia is proposed as a possible etiology for hemolysis.

PMID- 16085974
TI  - Anterior urethral valves.
AB  - Posterior urethral valves (PUV) are the most frequent cause of obstructive
      uropathy in boys. Rarer causes of obstructive uropathy include bladder
      diverticulae, meatal stenosis and urethral or bladder stones. Anterior urethral
      valves are rare causes of urinary obstruction in boys and are ten times less
      frequent than PUV in the literature(1-6). This paper highlights our experience
      with 5 patients with anterior urethral valves.

PMID- 16085975
TI  - Freeman-Sheldon syndrome.

PMID- 16085976
TI  - Complete penoscrotal transposition.

PMID- 16085977
TI  - Branding: a harmful practice.

PMID- 16085978
TI  - Enteroaggregative Escherichia coli diarrhea in Manipal.

PMID- 16085979
TI  - Validity of the shake test to identify the frozen damaged vaccine vials.

PMID- 16085980
TI  - Massive lipoblastoma foot.

PMID- 16085981
TI  - Primary lymphedema in a four year old boy.

PMID- 16085982
TI  - Polio eradication: let us face the facts and accept the reality.

PMID- 16085983
TI  - Bilateral communicating intralobar pulmonary sequestration.

PMID- 16085984
TI  - Analgesic effects of breastfeeding on heel lancing.

PMID- 16085985
TI  - Tobacco use among school students in India: the need for behavioral change.

PMID- 16085986
TI  - Diagnosing adrenal dysfunction in thalassemic children: a note of caution.

PMID- 16085988
TI  - Role of shunt surgery in pediatric tubercular meningitis with hydrocephalus.

PMID- 16085990
TI  - "Meaning-making" in language and biology.
AB  - The linguistic metaphor in biology adheres to a representational theory that
      seeks similarities between pre-given domains. The point of departure of this
      paper is the generative and nonrepresentational conception of metaphor. This
      paper argues that by adopting the nonrepresentational conception of metaphor,
      meaning-making may be the appropriate perspective for understanding biological
      systems. In both cases (the linguistic and the biological), boundary conditions
      between different levels of organization use micro-level disorganization to
      create macro-level organization.

PMID- 16085991
TI  - Ethical issues in animal cloning.
AB  - The issue of human reproductive cloning has recently received a great deal
      attention in public discourse. Bioethicists, policy makers, and the media have
      been quick to identify the key ethical issues involved in human reproductive
      cloning and to argue, almost unanimously, for an international ban on such
      attempts. Meanwhile, scientists have proceeded with extensive research agendas in
      the cloning of animals. Despite this research, there has been little public
      discussion of the ethical issues raised by animal cloning projects. Polling data
      show that the public is decidedly against the cloning of animals. To understand
      the public's reaction and fill the void of reasoned debate about the issue, we
      need to review the possible objections to animal cloning and assess the merits of
      the anti-animal cloning stance. Some objections to animal cloning (e.g., the
      impact of cloning on the population of unwanted animals) can be easily addressed,
      while others (e.g., the health of cloned animals) require more serious attention
      by the public and policy makers.

PMID- 16085992
TI  - Meeting threats to global health: a call for American leadership.
AB  - Although the application of major biomedical advances has yielded spectacular
      results for individual health, there has been little improvement in the health of
      whole populations. There is a "back to the future" irony in the fact that at the
      inception of the 21st century, the eruption and spread of a multitude of "old"
      and "new" infectious diseases has become the most serious global threat to the
      health of humankind. At this historical juncture, the United States is the
      country with the most potential for favorably influencing global health and
      health care. Although there are historical, cultural, economic, and political
      factors that impede the United States from rising to this challenge, there is
      both a moral imperative and a rational long-term self-interest basis for the U.S.
      medical profession and government to exercise leadership in facing the health
      challenges of tragic and genocidal proportions that threaten everyone in an
      increasingly interdependent world.

PMID- 16085993
TI  - Was Darwin a creationist?
AB  - Throughout the Origin of Species, Darwin contrasts his theory of natural
      selection with the theory that God independently created each species. This makes
      it seem as though the Origin offers a scientific alternative to a theological
      worldview. A few months after the Origin appeared, however, the eminent anatomist
      Richard Owen published a review that pointed out the theological assumptions of
      Darwin's theory. Owen worked in the tradition of rational morphology, within
      which one might suggest that evolution occurs by processes that are continuous
      with those by which life arises from matter; in contrast, Darwin rested his
      account of life's origins on the notion that God created one or a few life forms
      upon which natural selection could act. Owen argued that Darwin's reliance on God
      to explain the origins of life makes his version of evolution no less
      supernatural than the special creationist that Darwin criticizes: although Darwin
      limits God to one or a few acts of creation, he still relies upon God to explain
      life's existence.

PMID- 16085994
TI  - Hugh Ross's curious lymphocyte experiments.
AB  - It is now almost 100 years since Hugh Campbell Ross began his experiments on
      white blood cells and cancer. By suspending peripheral blood cells in a solution
      of agar gel, he was able to observe changes in them provoked by various natural
      and artificial substances, which he named auxetics, kinetics, or augmentors,
      depending on the effects they produced. After his early experience he focused his
      attention particularly on lymphocytes in peripheral blood samples; he claimed to
      have observed rapid division in them, although at that time they were looked upon
      as end cells without a future. He contended that his results challenged what had
      become the orthodox view of the role of the nucleus in mitosis, asserting that
      cytologists had been led astray by relying on examination of fixed, dead
      structures. When doubt was cast on his claim to have induced cell division, his
      brother Ronald, Nobel laureate in physiology or medicine, came to his defense,
      but to no avail, and although he continued his experiments for a number of years
      they were quietly forgotten. Fifty years later the occurrence of mitotic division
      of peripheral blood lymphocytes was established beyond any doubt by Nowell and
      Hirschhorn.

PMID- 16085995
TI  - The emergence of multiple sclerosis, 1870-1950: a puzzle of historical
      epidemiology.
AB  - In 1868, Jean-Martin Charcot identified multiple sclerosis (MS) as a distinct
      nosological entity. By 1870, American neurologists became aware of the "new"
      disease and began to diagnose cases in the United States. For the next 50 years,
      however, American physicians thought it was a rare condition. From 1920 to 1950,
      this perception changed dramatically; by 1950, neurologists considered it among
      the most common neurological diseases in America. The increasing prevalence of MS
      between 1920 and 1950 can largely be explained as an effect of an increase in the
      number of trained neurologists, urbanization, a changed ecology of disease, and
      altered concepts of gender and disease. Physicians recognized MS more frequently
      because over time there were more neurologists who had the skills necessary to
      make the difficult diagnosis, and because patients were more likely to be seen by
      a trained neurologist. Significant numbers of patients with MS had been
      misdiagnosed with other diseases such as hysteria and neurosyphilis; over time,
      they were increasingly diagnosed correctly.

PMID- 16085996
TI  - The bells are ringing: tinnitus in their own words.
AB  - Tinnitus, commonly known as "ringing in the ears," is the perception of a ringing
      noise or other sound within the head when none exists. It is a malady that
      affects millions, so its occurrence among the famous comes as no surprise.
      Beginning with Pliny the Elder, who coined the term, this essay describes the
      travails of a dozen well-known subjects afflicted with this disorder, through
      several centuries, principally in their own words. For some it was a burden to be
      endured; for others, it was unendurable. Suggested remedies were many and oft
      times strange; cure, even now, is nonexistent.

PMID- 16085997
TI  - A psychiatrist's life and the emerging of her creative eye.

PMID- 16085998
TI  - Why birdsong is sometimes like music.
AB  - The sounds and songs of birds have inspired the musical compositions of numerous
      cultures throughout the globe. This article examines a variety of compositions
      from Western music that feature birdsong and explores the concept of birds as
      both vocalists and instrumentalists. The concept of birds as composers is then
      developed-how they use rhythmic variations, pitch relationships, and combinations
      of notes similar to those found in music-and the theory that birds create
      variation in their songs partially to avoid monotony is considered. Various
      families of birds that borrow sounds from other species are surveyed, in
      particular the European starling (Sturnus vulgaris), which may have inspired a
      Mozart composition. We conclude that the fusion of avian bioacoustics and the
      study of birdsong in music may function as a conservation tool, raising the
      awareness of humans and stimulating future generations to save for posterity what
      remains of the natural world.

PMID- 16086001
TI  - The changing academic medical center.

PMID- 16086003
TI  - The epps factor: how brains trumped bigotry.

PMID- 16086004
TI  - Medications, rationing, and health care: the role of pharmacists in bridging the
      gap.

PMID- 16086005
TI  - Donated care programs: a stopgap measure or a long-run alternative to health
      insurance?
AB  - In the absence of broad federal health care reform, interest has grown in local
      solutions to the problem of providing health care to the uninsured. Community
      based donated medical care models have emerged as one alternative. We examine the
      early experience of a donated care program in southern Maine called CarePartners.
      Although such programs are often viewed as a short-term solution for those
      temporarily without health insurance, we find that CarePartners served a
      different role for many individuals. While clearly a stopgap measure for some
      enrollees, CarePartners appears to be a longer-term means for getting access to
      care for most enrollees.

PMID- 16086006
TI  - Reducing disparities in dental care for low-income Hispanic children.
AB  - Using a social ecological model, this study examined the influences of socio
      demographic factors, mother's attitudes, financial barriers, and the health care
      delivery system on the use of dental services for 4-8 year-old Hispanic children.
      Initiating dental care during the preschool years was significantly related to
      the mothers' beliefs and her social network's beliefs in the value of preventive
      dental care. The mother was almost four times more likely to continue the care if
      she believed that dentist visits would keep the child's teeth healthy. Extended
      clinic hours in the evenings also increased the likelihood of the mother's return
      to the dentist to continue child's care. It was not the mother's attitudes but
      provider availability, dental insurance (including Medicaid) and family income
      that were related to frequency of planned visits. The study findings can be used
      in improving access to care and reducing barriers for low-income, urban Hispanic
      children.

PMID- 16086007
TI  - Periods of unmanaged care in Medicaid managed care.
AB  - Churning in Medicaid has been long recognized as a problem leading to breaks in
      coverage. Tenure in Medicaid managed care has received less attention. Recent
      reports indicate that children's tenures in health plans are far shorter than
      tenures in Medicaid itself, but explanations for the difference are not given. In
      the research reported here, we conducted case studies in five states to determine
      difference in tenure and reasons for the difference. Our investigation showed
      that children were enrolled in Medicaid two to four months longer than in
      specific Medicaid health plans. The major reasons for the gap were retroactive
      enrollment in Medicaid and delays in selecting a health plan. Frequent and
      burdensome Medicaid renewal processes exacerbate the problem, resulting in breaks
      in enrollment and the need to reenroll. The task of managing the care of Medicaid
      children is difficult without adequate tenures in health plans.

PMID- 16086008
TI  - Uninsured adults aged 65 years and older: is their health at risk?
AB  - Some U.S. adults aged 65 years and older lack health care coverage. As a result,
      they may have unmet health needs and be vulnerable to excess morbidity and
      mortality. Due to their small numbers, little data on them exist. We used data
      from the 1996-2000 Behavioral Risk Factor Surveillance System, an ongoing
      telephone survey operated by the state health departments with assistance from
      the Centers for Disease Control and Prevention, to examine a representative
      sample of adults 65 years old and older. We found that blacks and Hispanics were
      disproportionately represented among uninsured older adults. Compared with their
      insured counterparts, the uninsured elderly experienced cost barriers to needed
      care, lacked receipt of an annual checkup, and did not receive preventive health
      screenings. Given the projected growth of the elderly population, particularly
      among blacks and Hispanics, it is crucial to ensure all older adults have access
      to preventive health services.

PMID- 16086009
TI  - The financial impact of interim and prospective payment systems on home health
      providers in rural communities.
AB  - The objective of the study was to examine the financial impact of the interim
      payment system and prospective payment system (PPS) on home health agencies
      (HHAs) in rural communities. Data sources used included a survey of
      administrators in all rural HHAs in Pennsylvania and financial and utilization
      data provided by 10 rural HHAs in Northwest Pennsylvania. The results of survey
      showed that, under the PPS, 40% of the HHAs reported financial vulnerability and
      24% expressed concern that the fiscal uncertainties arising from the PPS
      threatened their continued operation. Two prospective analyses were conducted to
      examine how HHAs would be further affected by payment rate changes implemented in
      October 2002 and April 2003. The Medicare margin in rural Pennsylvania was 23.3%
      during the period from October 2000 to June 2002. This margin was slightly higher
      than the free-standing home health Medicare margin (21.6%) reported in analyses
      conducted by the Medicare Payment Advisory Commission (MedPac). However, this
      Medicare margin did not include hospital-based HHAs. The payment rate changes
      implemented in 2002 and 2003 would increase the proportion of care episodes that
      incur financial losses, assuming service provision remains constant. As of April
      2003, the proportion of all episodes with loss would rise to 46.9%, the
      proportion of low-utilization payment adjustment (LUPA) episodes with loss would
      rise to 91.1%, and the proportion of non-LUPA episodes with loss would rise to
      40.2%. New payment mechanisms are profoundly affecting the finances of rural HHAs
      and the use of home health services by Medicare beneficiaries.

PMID- 16086010
TI  - The impact of welfare reforms, health, and insurance status on welfare
      recipients' health care access.
AB  - This study explores ways in which welfare reforms have affected utilization of
      four health services (physician visits, hospital care, prescription medication,
      and dentist visits) and the impact of health insurance on these services. A
      secondary data analysis of a nationally representative sample of 1,259 non
      elderly adult current and former welfare recipients shows that use of health
      services is significantly affected by state-specific welfare policy, health
      insurance, and race/ethnicity, when other variables are controlled. More
      restrictive state welfare policies were variously associated with lower
      likelihood of using dental care, visiting a physician and using prescriptions.
      Non-Hispanic whites in the sample were more likely than members of other
      racial/ethnic groups to use prescriptions; Hispanics were less likely than non
      Hispanic whites to visit physicians or dentists. The proportion of respondents
      reporting fair or poor health was three times as great as the estimated
      proportion of non-elderly adults reporting fair or poor health in the general
      population. Policy implications are discussed.

PMID- 16086013
TI  - A GTPase-activating protein controls Rab5 function in endocytic trafficking.
AB  - Rab-family GTPases are conserved regulators of membrane trafficking that cycle
      between inactive GDP-bound and activated GTP-bound states. A key determinant of
      Rab function is the lifetime of the GTP-bound state. As Rabs have a low intrinsic
      rate of GTP hydrolysis, this process is under the control of GTP-hydrolysis
      activating proteins (GAPs). Due to the large number of Rabs and GAPs that are
      encoded by the human genome, it has proven difficult to assign specific
      functional relationships to these proteins. Here, we identify a Rab5-specific GAP
      (RabGAP-5), and show that RN-Tre (previously described as a Rab5 GAP) acts on
      Rab41. RabGAP-5 overexpression triggers a loss of the Rab5 effector EEA1 from
      endosomes and blocks endocytic trafficking. By contrast, depletion of RabGAP-5
      results in increased endosome size, more endosome-associated EEA1, and disrupts
      the trafficking of EGF and LAMP1. RabGAP-5 therefore limits the amount of
      activated Rab5, and thereby regulates trafficking through endosomes.

PMID- 16086014
TI  - Epimutation of the telomeric imprinting center region on chromosome 11p15 in
      Silver-Russell syndrome.
AB  - Silver-Russell syndrome (SRS, OMIM 180860) is a congenital disorder characterized
      by severe intrauterine and postnatal growth retardation, dysmorphic facial
      features and body asymmetry. SRS is genetically heterogenous with maternal
      uniparental disomy with respect to chromosome 7 occurring in approximately 10% of
      affected individuals. Given the crucial role of the 11p15 imprinted region in the
      control of fetal growth, we hypothesized that dysregulation of genes at 11p15
      might be involved in syndromic intrauterine growth retardation. We identified an
      epimutation (demethylation) in the telomeric imprinting center region ICR1 of the
      11p15 region in several individuals with clinically typical SRS. This epigenetic
      defect is associated with, and probably responsible for, relaxation of imprinting
      and biallelic expression of H19 and downregulation of IGF2. These findings
      provide new insight into the pathogenesis of SRS and strongly suggest that the
      11p15 imprinted region, in addition to those of 7p11.2-p13 and 7q31-qter, is
      involved in SRS.

PMID- 16086015
TI  - Intragenic tandem repeats generate functional variability.
AB  - Tandemly repeated DNA sequences are highly dynamic components of genomes. Most
      repeats are in intergenic regions, but some are in coding sequences or
      pseudogenes. In humans, expansion of intragenic triplet repeats is associated
      with various diseases, including Huntington chorea and fragile X syndrome. The
      persistence of intragenic repeats in genomes suggests that there is a
      compensating benefit. Here we show that in the genome of Saccharomyces
      cerevisiae, most genes containing intragenic repeats encode cell-wall proteins.
      The repeats trigger frequent recombination events in the gene or between the gene
      and a pseudogene, causing expansion and contraction in the gene size. This size
      variation creates quantitative alterations in phenotypes (e.g., adhesion,
      flocculation or biofilm formation). We propose that variation in intragenic
      repeat number provides the functional diversity of cell surface antigens that, in
      fungi and other pathogens, allows rapid adaptation to the environment and elusion
      of the host immune system.

PMID- 16086016
TI  - Contributions of low molecule number and chromosomal positioning to stochastic
      gene expression.
AB  - The presence of low-copy-number regulators and switch-like signal propagation in
      regulatory networks are expected to increase noise in cellular processes. We
      developed a noise amplifier that detects fluctuations in the level of low
      abundance mRNAs in yeast. The observed fluctuations are not due to the low number
      of molecules expressed from a gene per se but originate in the random, rare
      events of gene activation. The frequency of these events and the correlation
      between stochastic expressions of genes in a single cell depend on the
      positioning of the genes along the chromosomes. Transcriptional regulators
      produced by such random expression propagate noise to their target genes.

PMID- 16086017
TI  - The Jak-STAT signaling pathway is required but not sufficient for the antiviral
      response of drosophila.
AB  - The response of drosophila to bacterial and fungal infections involves two
      signaling pathways, Toll and Imd, which both activate members of the
      transcription factor NF-kappaB family. Here we have studied the global
      transcriptional response of flies to infection with drosophila C virus. Viral
      infection induced a set of genes distinct from those regulated by the Toll or Imd
      pathways and triggered a signal transducer and activator of transcription (STAT)
      DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch
      was involved in the control of the viral load in infected flies and was required
      but not sufficient for the induction of some virus-regulated genes. Our results
      indicate that in addition to Toll and Imd, a third, evolutionary conserved innate
      immunity pathway functions in drosophila and counters viral infection.

PMID- 16086018
TI  - Function of NKG2D in natural killer cell-mediated rejection of mouse bone marrow
      grafts.
AB  - Irradiation-resistant natural killer (NK) cells in an F(1) recipient can reject
      parental bone marrow, and host NK cells can also prevent engraftment of
      allogeneic bone marrow. We show here that repopulating bone marrow cells in
      certain mouse strains expressed retinoic acid early inducible 1 proteins, which
      are ligands for the activating NKG2D NK cell receptor. Treatment with a
      neutralizing antibody to NKG2D prevented rejection of parental BALB/c bone marrow
      in (C57BL/6 x BALB/c) F(1) recipients and allowed engraftment of allogeneic
      BALB.B bone marrow in C57BL/6 recipients. Additionally, bone marrow from C57BL/6
      mice transgenic for retinoic acid early inducible 1epsilon was rejected by
      syngeneic mice but was accepted after treatment with antibody to NKG2D. If other
      stem cells or tissues upregulate expression of NKG2D ligands after
      transplantation, NKG2D may contribute to graft rejection in immunocompetent
      hosts.

PMID- 16086019
TI  - Immune evasion by a staphylococcal complement inhibitor that acts on C3
      convertases.
AB  - The complement system is pivotal in host defense but also contributes to tissue
      injury in several diseases. The assembly of C3 convertases (C4b2a and C3bBb) is a
      prerequisite for complement activation. The convertases catalyze C3b deposition
      on activator surfaces. Here we describe the identification of staphylococcal
      complement inhibitor, an excreted 9.8-kilodalton protein that blocks human
      complement by specific interaction with C4b2a and C3bBb. Staphylococcal
      complement inhibitor bound and stabilized C3 convertases, interfering with
      additional C3b deposition through the classical, lectin and alternative
      complement pathways. This led to a substantial decrease in phagocytosis and
      killing of Staphylococcus aureus by human neutrophils. As a highly active and
      small soluble protein that acts exclusively on surfaces, staphylococcal
      complement inhibitor may represent a promising anti-inflammatory molecule.

PMID- 16086020
TI  - On-demand release of corrosion-inhibiting ions from amorphous Al-Co-Ce alloys.
AB  - Controlled release technologies are often used to supply chemicals or drugs at
      given rates. Release often occurs on contact with solution. However, some
      applications, such as corrosion protection, require containment of the active
      species in a reservoir and their slow release when needed. Conductive polymers
      have been used as reservoirs for corrosion inhibitors whose triggered release
      occurs by galvanic reduction or ion exchange. This work shows one of the first
      examples of pH-controlled release of corrosion-inhibiting ions from an amorphous
      metallic coating where the pH change that triggers release is a consequence of
      the onset of corrosion. This corrosion-inhibition strategy provides further
      corrosion protection beyond the traditional roles of barrier and sacrificial
      cathodic protection using a metal coating. For instance, zinc galvanizing
      provides sacrificial cathodic protection and acts as a barrier, but does not
      supply inhibitor ions. In the coating described here, protection of an underlying
      structural alloy exposed at coating defects is demonstrated by inhibitor ion
      release in addition to barrier function and sacrificial cathodic protection.

PMID- 16086021
TI  - Quantitative equivalence between polymer nanocomposites and thin polymer films.
AB  - The thermomechanical responses of polymers, which provide limitations to their
      practical use, are favourably altered by the addition of trace amounts of a
      nanofiller. However, the resulting changes in polymer properties are poorly
      understood, primarily due to the non-uniform spatial distribution of
      nanoparticles. Here we show that the thermomechanical properties of 'polymer
      nanocomposites' are quantitatively equivalent to the well-documented case of
      planar polymer films. We quantify this equivalence by drawing a direct analogy
      between film thickness and an appropriate experimental interparticle spacing. We
      show that the changes in glass-transition temperature with decreasing
      interparticle spacing for two filler surface treatments are quantitatively
      equivalent to the corresponding thin-film data with a non-wetting and a wetting
      polymer-particle interface. Our results offer new insights into the role of
      confinement on the glass transition, and we conclude that the mere presence of
      regions of modified mobility in the vicinity of the particle surfaces, that is, a
      simple two-layer model, is insufficient to explain our results. Rather, we
      conjecture that the glass-transition process requires that the interphase regions
      surrounding different particles interact.

PMID- 16086022
TI  - Polymer hollow particles with controllable holes in their surfaces.
AB  - Colloidal particles with hollow interiors play important roles in
      microencapsulation-a process that has found widespread use in applications such
      as controlled release of drugs, cosmetics, inks, pigments or chemical reagents;
      protection of biologically active species; and removal of pollutants. The hollow
      particles are most commonly prepared by coating the surfaces of colloidal
      templates with thin layers of the desired material (or its precursor), followed
      by selective removal of the templates by means of calcination or chemical
      etching. This simple and straightforward approach works for a variety of
      materials that include polymers, ceramics, composites and metals. For polymers,
      methods such as emulsion polymerization, phase separation, crosslinking of
      micelles and self-assembly have also been demonstrated for generating hollow
      structures. However, diffusion through these closed shells with pores <10 nm is
      often a slow process. To solve this problem, macroporous capsules have been
      fabricated by organizing colloids around liquid droplets to form colloidosomes or
      by controlling the mixing of liquid droplets. Here we report the preparation of
      another class of macroporous capsules-polymer shells with controllable holes in
      their surfaces. After loading of functional materials, the holes can be closed by
      means of thermal annealing or solvent treatment.

PMID- 16086023
TI  - Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte
      progenitor maturation.
AB  - Demyelination is the hallmark of numerous neurodegenerative conditions, including
      multiple sclerosis. Oligodendrocyte progenitors (OPCs), which normally mature
      into myelin-forming oligodendrocytes, are typically present around demyelinated
      lesions but do not remyelinate affected axons. Here, we find that the
      glycosaminoglycan hyaluronan accumulates in demyelinated lesions from individuals
      with multiple sclerosis and in mice with experimental autoimmune
      encephalomyelitis. A high molecular weight (HMW) form of hyaluronan synthesized
      by astrocytes accumulates in chronic demyelinated lesions. This form of
      hyaluronan inhibits remyelination after lysolecithin-induced white matter
      demyelination. OPCs accrue and do not mature into myelin-forming cells in
      demyelinating lesions where HMW hyaluronan is present. Furthermore, the addition
      of HMW hyaluronan to OPC cultures reversibly inhibits progenitor-cell maturation,
      whereas degrading hyaluronan in astrocyte-OPC cocultures promotes oligodendrocyte
      maturation. HMW hyaluronan may therefore contribute substantially to
      remyelination failure by preventing the maturation of OPCs that are recruited to
      demyelinating lesions.

PMID- 16086024
TI  - Multiple diagnostic techniques identify previously vaccinated individuals with
      protective immunity against monkeypox.
AB  - Approximately 50% of the US population received smallpox vaccinations before
      routine immunization ceased in 1972 for civilians and in 1990 for military
      personnel. Several studies have shown long-term immunity after smallpox
      vaccination, but skepticism remains as to whether this will translate into full
      protection against the onset of orthopoxvirus-induced disease. The US monkeypox
      outbreak of 2003 provided the opportunity to examine this issue. Using
      independent and internally validated diagnostic approaches with >or=95%
      sensitivity and >or=90% specificity for detecting clinical monkeypox infection,
      we identified three previously unreported cases of monkeypox in preimmune
      individuals at 13, 29 and 48 years after smallpox vaccination. These individuals
      were unaware that they had been infected because they were spared any
      recognizable disease symptoms. Together, this shows that the US monkeypox
      outbreak was larger than previously realized and, more importantly, shows that
      cross-protective antiviral immunity against West African monkeypox can
      potentially be maintained for decades after smallpox vaccination.

PMID- 16086025
TI  - Chromatin remodeling through directional DNA translocation from an internal
      nucleosomal site.
AB  - The RSC chromatin remodeler contains Sth1, an ATP-dependent DNA translocase. On
      DNA substrates, RSC/Sth1 tracks along one strand of the duplex with a 3' --> 5'
      polarity and a tracking requirement of one base, properties that may enable
      directional DNA translocation on nucleosomes. The binding of RSC or Sth1 elicits
      a DNase I-hypersensitive site approximately two DNA turns from the nucleosomal
      dyad, and the binding of Sth1 requires intact DNA at this location. Results with
      various nucleosome substrates suggest that RSC/Sth1 remains at a fixed position
      on the histone octamer and that Sth1 conducts directional DNA translocation from
      a location about two turns from the nucleosomal dyad, drawing in DNA from one
      side of the nucleosome and pumping it toward the other. These studies suggest
      that nucleosome mobilization involves directional DNA translocation initiating
      from a fixed internal site on the nucleosome.

PMID- 16086026
TI  - Regulated degradation of replication-dependent histone mRNAs requires both ATR
      and Upf1.
AB  - Eukaryotic cells coordinately regulate histone and DNA synthesis. In mammalian
      cells, most of the regulation of histone synthesis occurs post-transcriptionally
      by regulating the concentrations of histone mRNA. As cells enter S phase, histone
      mRNA levels increase, and at the end of S phase they are rapidly degraded.
      Moreover, inhibition of DNA synthesis causes rapid degradation of histone mRNAs.
      Replication-dependent histone mRNAs are the only metazoan mRNAs that are not
      polyadenylated. Instead, they end with a conserved stem-loop structure, which is
      the only cis-acting element required for coupling regulation of histone mRNA half
      life with DNA synthesis. Here we show that regulated degradation of histone mRNAs
      requires Upf1, a key regulator of the nonsense-mediated decay pathway, and ATR, a
      key regulator of the DNA damage checkpoint pathway activated during replication
      stress.

PMID- 16086027
TI  - Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and
      methoxsalen.
AB  - Human microsomal cytochrome P450 2A6 (CYP2A6) contributes extensively to nicotine
      detoxication but also activates tobacco-specific procarcinogens to mutagenic
      products. The CYP2A6 structure shows a compact, hydrophobic active site with one
      hydrogen bond donor, Asn297, that orients coumarin for regioselective oxidation.
      The inhibitor methoxsalen effectively fills the active site cavity without
      substantially perturbing the structure. The structure should aid the design of
      inhibitors to reduce smoking and tobacco-related cancers.

PMID- 16086031
TI  - The role of p38 MAPK activation in auranofin-induced apoptosis of human
      promyelocytic leukaemia HL-60 cells.
AB  - In a previous study, we reported an antileukaemic activity of auranofin (AF),
      demonstrating its dual effects: on the induction of apoptotic cell death and its
      synergistic action with retinoic acid on cell differentiation. In this study, we
      investigated the downstream signalling events of AF-induced apoptosis to
      determine the molecular mechanisms of AF activity. Treatment of HL-60 cells with
      AF induced apoptosis in a concentration- and time-dependent manner. Western blot
      analysis showed that AF-induced apoptosis was accompanied by the activation of
      caspase-8, caspase-9, and caspase-3, and the release of cytochrome c from the
      mitochondria. The phosphorylation and kinase activities of p38 mitogen-activated
      protein kinase (p38 MAPK) increased gradually until 12 h after AF (2 microM)
      treatment, and p38 MAPK was also activated concentration-dependently.
      Pretreatment with SB203580, a specific inhibitor of p38 MAPK, significantly
      blocked DNA fragmentation and the cleavage of procaspase-8, procaspase-3, and
      poly-ADP-ribose polymerase (PARP), whereas SB203580 alone had no effect. Reactive
      oxygen species (ROS) were also detected within 1 h after AF treatment, and the
      antioxidant N-acetyl-L-cysteine (NAC) effectively protected the cells from
      apoptosis by inhibiting the phosphorylation of p38 MAPK and the activation of
      caspases. These results suggest that ROS generation and the subsequent activation
      of p38 MAPK are essential for the proapoptotic effects of AF in human
      promyelocytic leukaemia HL-60 cells.

PMID- 16086030
TI  - Induction of central signalling pathways and select functional effects in human
      platelets by beta-boswellic acid.
AB  - We have recently shown that in polymorphonuclear leukocytes, 11-keto boswellic
      acids (KBAs) induce Ca2+ mobilisation and activation of mitogen-activated protein
      kinases (MAPK). Here we addressed the effects of BAs on central signalling
      pathways in human platelets and on various platelet functions. We found that beta
      BA (10 microM), the 11-methylene analogue of KBA, caused a pronounced
      mobilisation of Ca2+ from internal stores and induced the phosphorylation of p38
      MAPK, extracellular signal-regulated kinase (ERK)2, and Akt. These effects of
      beta-BA were concentration dependent, and the magnitude of the responses was
      comparable to those obtained after platelet stimulation with thrombin or
      collagen. Based on inhibitor studies, beta-BA triggers Ca2+ mobilisation via the
      phospholipase (PL)C/inositol-1,4,5-trisphosphate pathway, and involves Src family
      kinase signalling. Investigation of platelet functions revealed that beta-BA (>
      or =10 microM) strongly stimulates the platelet-induced generation of thrombin in
      an ex-vivo in-vitro model, the liberation of arachidonic acid (AA), and induces
      platelet aggregation in a Ca2+-dependent manner. In contrast to beta-BA, the 11
      keto-BAs (KBA or AKBA) evoke only moderate Ca2+ mobilisation and activate p38
      MAPK, but fail to induce phosphorylation of ERK2 or Akt, and do not cause
      aggregation or significant generation of thrombin. In summary, beta-BA potently
      induces Ca2+ mobilisation as well as the activation of pivotal protein kinases,
      and elicits functional platelet responses such as thrombin generation, liberation
      of AA, and aggregation.

PMID- 16086032
TI  - Abolition of chondral mineralization by group III metabotropic glutamate
      receptors expressed in rodent cartilage.
AB  - 1 Previous studies have demonstrated the functional expression by osteoblasts of
      glutamate (Glu) signaling machineries responsible for the stimulation of cell
      proliferation and differentiation in bone, while there is no information
      available on the expression of the Glu signaling system by cartilage to date. 2
      In cultured mouse embryonic metatarsals isolated before vascularization, chondral
      mineralization was almost completely inhibited in the presence of the group III
      metabotropic Glu receptor (mGluR) agonist L-(1)-2-amino-4-phosphonobutyrate (L
      AP4) in a manner sensitive to an antagonist, with the total length being
      unchanged. 3 A group II mGluR agonist was similarly more effective in inhibiting
      the mineralization than a group I mGluR agonist, while none of ionotropic GluR
      agonists drastically affected the mineralization. 4 Both histological and in situ
      hybridization analyses revealed that L-AP4 specifically inhibited chondral
      mineralization, without apoptotic cell death, in cultured metatarsals. 5 In
      addition to the constitutive expression of mRNA for particular mGluRs in both
      cultured mouse metatarsals and rat costal chondrocytes, L-AP4 significantly
      inhibited the accumulation of cyclic AMP by forskolin and parathyroid hormone in
      a manner sensitive to a group III mGluR antagonist in cultured chondrocytes. 6
      Moreover, L-AP4 drastically inhibited the expression of osteopontin mRNA in both
      cultured metatarsals and chondrocytes. 7 These results suggest that Glu may at
      least in part play a role as a signal mediator in mechanisms associated with
      chondral mineralization through the group III mGluR subtype functionally
      expressed by chondrocytes in rodent cartilage.

PMID- 16086033
TI  - The neurochemical and behavioral effects of the novel cholinesterase-monoamine
      oxidase inhibitor, ladostigil, in response to L-dopa and L-tryptophan, in rats.
AB  - The novel drugs, ladostigil (TV3326) and TV3279, are R and S isomers,
      respectively, derived from a combination of the carbamate cholinesterase (ChE)
      inhibitor, rivastigmine, and the pharmacophore of the monoamine oxidase (MAO) B
      inhibitor, rasagiline. They were developed for the treatment of comorbidity of
      dementia with Parkinsonism. In the present study, we determined the effects of
      these drugs on both aminergic neurotransmitter levels and motor behavioral
      activity in naive and in L-dopa- or L-tryptophan-induced rats. Chronic treatment
      of rats with ladostigil (52 mg kg(-1) for 21 days) inhibited hippocampal and
      striatal MAO A and B activities by >90%, increased striatal levels of dopamine
      and serotonin, and inhibited striatal ChE activity by approximately 50%. Chronic
      TV3279 (26 mg kg(-1) for 21 days) similarly inhibited approximately 50% of
      striatal ChE activity, but did not affect MAO activity or amine levels. In sharp
      contrast to the inductive effect of the MAO A/B inhibitor, tranylcypromine (TCP),
      on stereotyped hyperactivity in response to L-dopa (50 mg kg(-1)) or L-tryptophan
      (100 mg kg(-1)), ladostigil completely inhibited these behavioral hyperactivity
      syndromes. Accordingly, acute rivastigmine (2 mg kg(-1)) and chronic TV3279
      abolished the ability of TCP to initiate L-dopa-induced hyperactivity, while
      scopolamine (0.5 mg kg(-1)) reversed the inhibitory effect of chronic ladostigil
      on L-dopa-induced hyperactivity, suggesting that ladostigil may attenuate
      successive locomotion by activating central cholinergic muscarinic
      receptors.Finally, while chronic ladostigil administration to naive rats resulted
      in preserved spontaneous motor behavior, acute treatment with ladostigil
      decreased motor performance, compared to control animals. In contrast, chronic as
      well as acute treatments with TV3279 reduced spontaneous motor activity. Thus,
      the aminergic potentiation by ladostigil may counteract its cholinergic
      inhibitory effect on spontaneous motor behavior. Our results suggest that
      potentiation of both aminergic and cholinergic transmission systems by ladostigil
      contributes equally to motor behavior performance, which is substantially
      impaired in comorbidity of dementia with Parkinsonism including dementia with
      Lewy bodies (DLB).

PMID- 16086034
TI  - Intracellular pathways triggered by the selective FLT-1-agonist placental growth
      factor in vascular smooth muscle cells exposed to hypoxia.
AB  - We have previously shown that hypoxia makes vascular smooth muscle cells (VSMCs)
      responsive to placental growth factor (PlGF) through the induction of functional
      fms-like tyrosine kinase (Flt-1) receptors. The aim of this study was to
      investigate the molecular mechanisms involved in the PlGF effects on
      proliferation and contraction of VSMCs previously exposed to hypoxia (3% O2). In
      cultured rat VSMCs exposed to hypoxia, PlGF increased the phosphorylation of
      protein kinase B (Akt), p38 and STAT3; activation of STAT3 was higher than that
      of other kinases. In agreement with this finding, the proliferation of hypoxia
      treated VSMCs in response to PlGF was significantly impaired by the p38 and the
      phosphatidylinositol 3-kinase inhibitors SB202190 and LY294002, respectively, and
      was almost completely prevented by AG490, a janus tyrosine kinase (JAK)/signal
      transducer and activator of transcription (STAT) inhibitor. Since hypoxia was
      able to reverse the vasorelaxant effect of PlGF into a vasoconstrictor response,
      the mechanism of this latter effect was also investigated. Significant Flt-1
      activity was measured in isolated preparations from rat aorta exposed to hypoxia.
      Inhibitors of mitogen-activated protein kinase kinase, Akt and STAT3 induced a
      modest inhibition of the vasoconstrictor response to PlGF, while the p38
      inhibitor SB202190 markedly impaired the PlGF-induced contractile response. These
      effects were selectively mediated by Flt-1 without any involvement of foetal
      liver kinase-1 receptors. These data are the first evidence that different
      intracellular pathways activated by Flt-1 receptor in VSMCs are involved in
      diverse biological effects of PlGF: while mitogen activated protein kinase
      kinase/extracellular signal regulated kinase(1/2) and JAK/STAT play a role in
      VSMC proliferation, p38 is involved in VSMC contraction. These findings may
      highlight the role of PlGF in vascular pathology.

PMID- 16086035
TI  - Clathrin-independent internalization of the human histamine H1-receptor in CHO-K1
      cells.
AB  - The aim of the present study was to investigate the cellular pathway involved in
      histamine-stimulated internalization of the human H1-receptor in CHO-K1 cells
      expressing N-terminal myc-tagged H1-receptor (Myc-H1) or N-terminal myc-C
      terminal green fluorescent protein (Myc-GFP H1) versions of the receptor. Studies
      of 3H-mepyramine binding and histamine-stimulated 3H-inositol phosphate
      accumulation in these cells showed that the Myc-H1 and Myc-GFP H1-receptors had
      identical pharmacology to the wild-type H1-receptor. The Myc-H1-receptor was
      rapidly internalized in CHO-K1 cells following stimulation with histamine (0.1
      mM). This response occurred within 15 min, and could be prevented by the
      quaternary H1-receptor antagonist alpha-pirdonium. Similar data were obtained
      with the Myc-GFP H1-receptors. Internalization of the Myc-GFP H1-receptor was
      maintained in the absence of extracellular calcium and was not inhibited by the
      CAM kinase II inhibitor KN-62 (10 microM). Phorbol dibutyrate, an activator of
      protein kinase C, was also able to stimulate internalization of the H1-receptor.
      However, inhibition or downregulation of protein kinase C (which significantly
      modified histamine-stimulated inositol phosphate responses) was without effect on
      the internalization of the H1-receptor stimulated by histamine. Hypertonic
      sucrose did not prevent histamine-induced internalization of the Myc-GFP H1
      receptor, but was able to attenuate internalization of transferrin via clathrin
      mediated endocytosis in the same cells. In contrast, preincubation of cells with
      filipin or nystatin, which disrupts caveolae and lipid rafts, completely
      inhibited the histamine-induced internalization of the Myc-GFP H1-receptor, but
      was without effect on the sequestration of transferrin. The H1-receptor and
      cholera toxin subunit B were colocalized under resting conditions at the cell
      surface. Immunohistochemical studies with an antibody to caveolin-1 confirmed
      that this protein was also localized predominantly to the plasma membrane.
      However, following stimulation of CHO-Myc-GFP H1 cells with histamine, there was
      no evidence for internalization of caveolin-1 in parallel with the H1-receptor.
      These data provide strong evidence that the H1-receptor is internalized via a
      clathrin-independent mechanism and most likely involves lipid rafts.

PMID- 16086036
TI  - Neuroprotective effect of paeoniflorin on cerebral ischemic rat by activating
      adenosine A1 receptor in a manner different from its classical agonists.
AB  - The effects of paeoniflorin (PF), a compound isolated from Paeony radix, on
      neurological impairment and histologically measured infarction volume following
      transient and permanent focal ischemia were examined in Sprague-Dawley rats. In
      transient ischemia model, rats were subjected to a 1.5-h occlusion of the middle
      cerebral artery (MCA). The administration of PF (2.5 and 5 mg kg(-1), s.c.)
      produced a dose-dependent decrease in both neurological impairment and the
      histologically measured infarction volume. Similar results were also obtained
      when PF (2.5, 5, and 10 mg kg(-1), s.c.) was given in permanent ischemia model.
      The neuroprotective effect of PF (10 mg kg(-1), s.c.) was abolished by
      pretreatment of DPCPX (0.25 mg kg(-1), s.c.), a selective adenosine A1 receptor
      (A1R) antagonist. PF (10, 40, and 160 mg kg(-1), i.v.) had no effect on mean
      arterial pressure (MAP) and heart rates (HR) in the conscious rat. Additionally,
      PF (10(-3) mol l(-1)) had no effect on noradrenaline- (NA-) or high K+
      concentration-induced contractions of isolated rabbit primary artery. In
      competitive binding experiments, PF did not compete with the binding of
      [3H]DPCPX, but displaced the binding of [3H]NECA to the membrane preparation of
      rat cerebral cortex. This binding manner was distinguished from the classical A1R
      agonists. The results demonstrated that activation of A1R might be involved in PF
      induced neuroprotection in cerebral ischemia in rat. However, PF had no 'well
      known' cardiovascular side effects of classical A1R agonists. The results suggest
      that PF might have the potential therapeutic value as an anti-stroke drug.

PMID- 16086038
TI  - Photodynamic therapy with verteporfin for juxtafoveal choroidal
      neovascularisation secondary to pathological myopia.

PMID- 16086037
TI  - Mechanisms of xenon- and isoflurane-induced preconditioning - a potential link to
      the cytoskeleton via the MAPKAPK-2/HSP27 pathway.
AB  - We previously demonstrated that the anesthetic gas xenon exerts cardioprotection
      by preconditioning in vivo via activation of protein kinase C (PKC)-epsilon and
      p38 mitogen-activated protein kinase (MAPK). P38 MAPK interacts with the actin
      cytoskeleton via the MAPK-activated protein kinase-2 (MAPKAPK-2) and heat-shock
      protein 27 (HSP27). The present study further elucidated the underlying molecular
      mechanism of xenon-induced preconditioning (Xe-PC) by focusing on a potential
      link of xenon to the cytoskeleton. Anesthetized rats received either xenon (Xe
      PC, n = 6) or the volatile anesthetic isoflurane (Iso-PC, n = 6) during three 5
      min periods interspersed with two 5-min and one final 10-min washout period.
      Control rats (n = 6) remained untreated for 45 min. Additional rats were either
      pretreated with the PKC inhibitor Calphostin C (0.1 mg kg(-1)) or with the p38
      MAPK inhibitor SB203580 (1 mg kg(-1)) with and without anesthetic preconditioning
      (each, n = 6). Hearts were excised for immunohistochemistry of F-actin fibers and
      phosphorylated HSP27. Phosphorylation of MAPKAPK-2 and HSP27 were assessed by
      Western blot. HSP27 and actin colocalization were investigated by co
      immunoprecipitation. Xe-PC induced phosphorylation of MAPKAPK-2 (control 1.0 +/-
      0.2 vs Xe-PC 1.6 +/- 0.1, P < 0.05) and HSP27 (control 5.0 +/- 0.5 vs Xe-PC 9.8
      +/- 1.0, P < 0.001). Both effects were blocked by Calphostin C and SB203580. Xe
      PC enhanced translocation of HSP27 to the particulate fraction and increased F
      actin polymerization. F-actin and pHSP27 were colocalized after Xe-PC. Xe-PC
      activates MAPKAPK-2 and HSP27 downstream of PKC and p38 MAPK. These data link Xe
      PC to the cytoskeleton, revealing new insights into the mechanisms of Xe-PC in
      vivo.

PMID- 16086039
TI  - Anti-TNF-alpha therapy for uveitis: Behcet and beyond.

PMID- 16086041
TI  - Rhabdomyolysis after concomitant use of cyclosporine and simvastatin in a patient
      transplanted for multiple myeloma.

PMID- 16086042
TI  - Donor cell-derived myelodysplastic syndrome in a patient 7 years after unrelated
      allogeneic HLA-mismatched transplantation for Ph+ chronic myeloid leukemia.

PMID- 16086043
TI  - A safety evaluation of drotrecogin alfa (activated) in hematopoietic stem cell
      transplant patients with severe sepsis: lessons in clinical research.
AB  - We conducted an open-label, multicenter, single-arm clinical trial to investigate
      the safety and efficacy of drotrecogin alfa (activated) (Drot AA) in
      hematopoietic stem cell transplant (HSCT) patients with severe sepsis. Drot AA
      was administered as a continuous i.v. infusion of 24 microg/kg/h for 96 h. The
      target enrollment was 250 patients in 15-20 transplant centers over a 2-year
      period (March 2003-March 2005). However, after only 10 months, in December 2003,
      the trial was stopped due to a low enrollment of seven patients at three of the
      15 sites that were open for accrual. Six of the seven patients completed the drug
      infusion. Two patients experienced serious bleeding events. The first patient
      developed a nonfatal diffuse alveolar hemorrhage 2 days after study-drug
      completion. The second patient had severe coagulopathy and developed a fatal
      intracranial hemorrhage on the third day of drug infusion. Three of the seven
      patients were alive 100 days after the HSCT. The slow enrollment rate was
      attributed to changes in transplant preparatory regimens, enhancements in
      antimicrobial prophylactic protocols and the use of antimicrobial-coated
      catheters. The small number of patients in this report precludes a definitive
      assessment of the safety and efficacy of Drot AA in HSCT patients.

PMID- 16086044
TI  - Characteristics and correlates of cognitive functioning following bone marrow
      transplantation.
AB  - Patients who undergo bone marrow transplantation (BMT) often report cognitive
      problems following treatment. This study used cognitive tests and a self-report
      measure of subjective cognitive complaints to determine (1) the rate of objective
      cognitive impairment in a sample of 65 BMT patients, and (2) the correspondence
      of patients' cognitive complaints to their actual cognitive performance. At 6
      months following BMT, patients were assessed in seven cognitive domains-
      attention, verbal learning, verbal memory, visual memory, simple executive
      function, complex executive function, and psychomotor speed. Cognitive complaints
      were likewise assessed. In all, 51% had at least mild impairment (-1 standard
      deviation (s.d.) below published norms) in one or more cognitive domains, with
      28% demonstrating moderate-to-severe impairment (-2 s.d.). Older patients and
      patients with lower IQ were more likely to score in the impaired range on
      objective cognitive tests, with males and the less educated showing trends toward
      scores in the impaired range. Younger patients made significantly more cognitive
      complaints. Total cognitive complaints were unrelated to average cognitive
      performance, and complaints in specific cognitive domains were largely unrelated
      to objective performance on corresponding domains. Findings suggest that patients
      who complain about their cognitive performance following BMT differ from those
      who experience actual deficits.

PMID- 16086045
TI  - Change in stem cell source for hematopoietic stem cell transplantation (HSCT) in
      Europe: a report of the EBMT activity survey 2003.
AB  - This EBMT activity survey presents the status of hematopoietic stem cell
      transplantation (HSCT) in Europe 2003 and focuses on changes in stem cell source
      over the last decade. There were 21 028 first HSCT, 7091 allogeneic (34%), 13 937
      autologous (66%) and 4179 additional re- or multiple transplants reported from
      597 centers in 42 European countries in the year 2003. Main indications were
      leukemias (6613 (31%; 78% allogeneic)); lymphomas (11 571 (55%; 93% autologous));
      solid tumors (1792 (9%; 92% autologous)) and nonmalignant disorders (898 (5%; 93%
      allogeneic)). In 1991, the vast majority of autologous and all allogeneic HSCT
      were still bone marrow (BM) transplants. Stem cell source changed rapidly to
      peripheral blood (PB) for autologous HSCT between 1992 and 1996. In 2003, 97% of
      autologous HSCT were PB derived. The change to PB for allogeneic HSCT followed 3
      years later and occurred at a lower rate. In 2003, 65% of all allogeneic HSCT
      were PB derived. The change in stem cell source was not homogeneous. It was
      associated with donor type, main diagnosis, disease stage and it differed between
      European countries. In 2003, bone marrow remains a significant source of stem
      cells in some European countries for autologous HSCT and for nonmalignant
      disorders in allogeneic HSCT.

PMID- 16086046
TI  - A double-blind randomized placebo-controlled study of oral glutamine in the
      prevention of mucositis in children undergoing hematopoietic stem cell
      transplantation: a pediatric blood and marrow transplant consortium study.
AB  - Severe mucositis is a common cause of morbidity in hematopoietic stem cell
      transplant (HSCT) recipients. Glutamine has been shown to reduce mucositis in
      children receiving chemotherapy. Patients were randomized in a double-blind
      manner to receive glutamine or glycine at a dose of 2 g/m(2)/dose (maximum dose 4
      g) twice daily until 28 days post transplant or discharge if sooner. Mucositis
      was graded by use of a modified Walsh scale. A total of 120 children were
      evaluable: 57 children received glutamine and 63 received glycine. The mean
      mucositis score was 3.0+/-0.3 vs 3.9+/-0.4 (P=0.07) in the glutamine and glycine
      groups, respectively. The glutamine group demonstrated a reduction in mean number
      of days of intravenous narcotics use (12.1+/-1.5 vs 19.3+/-2.8 in the glycine
      group, P=0.03) and total parenteral nutrition (17.3+/-1.7 vs 27.3+/-3.6 in
      glycine group, P=0.01). There was no statistically significant difference in
      toxicity between the two groups. Glutamine appears to be safe and beneficial in
      reducing the severity of mucositis. Strong consideration should be given to
      include oral glutamine supplementation as a routine part of supportive care of
      SCT patients.

PMID- 16086047
TI  - [Epidemiological study on reduced folate carrier gene(RFC1 A80G) polymorphism and
      other risk factors of neural tube defects].
AB  - OBJECTIVE: To study the reduced folate carrier gene (RFC1) A80G polymorphism and
      other factors influence on children with neural tube defects (NTDs) and provide
      the epidemiological evidence for finding genetic marker of NTDs. METHODS:
      RFC1(A80G) genotypes were detected using polymerase chain reaction-restriction
      fragment length polymorphism (RFLP-PCR) for blood DNA of 104 trios with NTDs
      affected by child, and the 100 control families without child-affected by any
      birth defects. We performed the analysis of multifactors logistic regression for
      RFC1 genotypes and other factors in order to investigate the RFC1 genotype of the
      nuclear families and maternal periconceptional folic acid supplementation
      influence on NTDs independently. Transmission/disequilibrium test (TDT) for the
      RFC1 genotype of NTDs and control pedigree were carried out. RESULTS: The RFC1 G
      allele frequency of children with NTDs (64.42%) was higher than that of the
      control children (52.53%), and there was the significant difference between them
      (chi(2)=5.9198, P<0.05). We observed that the infants of the GG genotype were
      associated with a 2.56-fold increased risk of NTDs when compared with the AA
      genotype (95% CI=1.04-6.36), The risk of mothers who did not take folic acid for
      having an NTDs-affected infants was 7.69 (95% CI=2.86-21.75). There were
      significant differences between cases and controls in the other risk factors,
      such as paternal age (> or =30), maternal fever during the early pregnancy, the
      history of maternal spontaneous abortion. In the logistic regression analysis, of
      multifactors the three factors, for example, the offspring of the RFC1 GG
      genotype (OR=2.91, 95% CI=1.35-6.30), maternal periconceptional folic acid
      supplementation (OR=4.32, 95% CI=1.62-11.55), maternal fever during the early
      pregnancy, had the statistic significance for the risk of NTDs. There was the
      evidence of an association between G allele and the risk of the maternal having a
      child with NTDs (OR=1.56, 95% CI=1.07-2.28) in TDT analysis. CONCLUSION: Our
      findings indicate that the RFC1 genotype (GG) is a possible susceptible gene
      marker for an increased NTDs risk in this Chinese population, and there is a
      potential influence on the risk of NTDs in maternal periconceptional folic acid
      supplementation, and maternal fever during the early pregnancy.

PMID- 16086048
TI  - [In utero ethanol exposure alters the mitochondrial protein expression of fetal
      mouse cerebrum].
AB  - OBJECTIVE: To probe the effect of prenatal ethanol exposure on the mitochondrial
      protein expression in fetal mouse cerebrum. METHODS: Pregnant CD-1 mice were
      given 5.0 g/kg ethanol intragastrically from pregnant days (PD) 6-15. Fetal
      cerebral mitochondria were isolated on PD 18. The overall mitochondrial protein
      was applied to two-dimensional gel electrophoresis. Differentially expressed
      protein spots were cut off and identified by matrix-assisted laser desorption
      ionization time-of-flight (MALDI-TOF) mass spectrometry. Activities of
      respiratory chain complex IV (72.3%+/-4.6% of control) and ATP synthase, and ATP
      content in the fetal cerebral cells were measured. RESULTS: Expressions of some
      constructional and functional proteins were altered by in utero ethanol exposure.
      Activities of respiratory chain complex IV and ATP synthase (80.3%+/-5.1% of
      control) were both decreased. ATP content (67.9%+/-3.9% of control) in the
      cerebral cells was reduced in the in utero ethanol exposure fetuses. CONCLUSION:
      In utero ethanol exposure affects the mitochondrial protein expression of fetal
      mouse cerebrum, even in the tissue without obvious morphological malformations,
      which may be a possible mechanism of behavioral defects found in children with
      prenatal ethanol exposure.

PMID- 16086049
TI  - [Impaired islet beta-cell function and insulin resistance in adult male rats born
      with intrauterine growth retardation].
AB  - OBJECTIVE: To investigate the islet beta-cell function and insulin sensitivity in
      adult male rats born intrauterine growth retardation caused by uterine placenta
      insufficiency. METHODS: Bilateral uterine artery ligation (UAL) was performed on
      day 17 of gestation in the pregnant Wistar rats; sham-operated pregnant rats
      served as controls. The birth weights of the offspring in the UAL group were
      below the mean values of the birth weights of the control group more than 2SD,
      defined as IUGR. The tests were done in the adult male offspring (n=9 for each
      group). The glucose tolerance test was processed and Modified Beta-Cell function
      Index (MBCI) was calculated to evaluating the islet beta-cell endocrine function.
      Hyperinsulinemic-euglycemic clamp, the gold standard method to test the insulin
      resistance in the peripheral tissue was performed and insulin induced glucose
      infusion rate (GIR) was used to evaluate the insulin sensitivity. RESULTS: (1)
      Though the mean birth weight of the newborn in the UAL group (4.49+/-0.56) g is
      much more than two standard deviations below the mean weight of that of the
      control group (6.16+/-0.30) g, P<0.001. The body weights of the UAL adult male
      offspring (382+/-37.51) g were significantly higher than those of the control
      group(339+/-24.06) g, P<0.01; (2) During a glucose tolerance test, the glucose
      levels of the UAL adult offspring [0 min, (3.96 +/-0.25) mmol/L; 30 min, (6.61+/
      0.57) mmol/L; 60 min, (7.34+/-0.47) mmol/L; 120 min, (6.27+/-0.37) mmol/L] were
      significant higher than those of the controls [0 min, (3.56+/-0.22) mmol/L; 30
      min, (5.74+/-0.32) mmol/L; 60 min, (5.89+/-0.29) mmol/L; 120 min, (3.89+/-0.25)
      mmol/L], P<0.05. The peak of insulin secretion is delayed and the insulin level
      at 120 min (84.65+/-11.79) mU/L is much higher than that of the controls (50.01+/
      7.43) mU/L, P<0.05. MBCI values in the UAL adult male offspring (26.42+/-5.59) is
      significantly lower than those of in the control group (55.88+/-10.20), P<0.001.
      (3) The GIR in UAL adult offspring [16.86+/-1.59 mg/(kg . min)] is significantly
      lower than that of control group [20.35+/-2.38 mg/(kg . min)], P<0.05.
      CONCLUSION: The adult male rats born intrauterine growth retardation are prone to
      be obesity. The impaired islet beta-cell function and insulin resistance would be
      the risk factors for the development of type 2 diabetes mellitus.

PMID- 16086050
TI  - [Treatment of refractory and relapsed acute lymphocytic leukemia in adults].
AB  - OBJECTIVE: To analyze on the efficacy and toxicity of fludarabine and teniposide
      + mitoxantrone (MIT) regimens on treating refractory and relapsed acute
      lymphocytic leukemia in adult patients. METHODS: Teniposide 100 mg/d, 5-7 d, MIT
      10 mg/d, 2 d and fludarabine regimens [Flu 30 mg/(m(2) . d), 3- 5 d, Cytarabine
      (Ara-c )1-2 g/(m(2) . d), 5 d; Flu 50 mg/d, 5 d, Ara-c 200 mg/d, 5 d, MIT 4 mg/d,
      4 d] were used to treat 42 cases of adults with refractory and relapsed acute
      lymphocytic leukemia(ALL). G-CSF 5 microg/(kg . d) were used when WBC<1.0 x
      10(9)/L. RESULTS: In both the regimens fludarabine and VM (teniposide + MIT), the
      complete remission (CR) rate was 45% versus 31.8% (P>0.05); the median
      neutropenia began 6 days after the regimens arresting and lasting 10 versus 7.5
      days, P>0.05; thrombocytopenia begin at time of 10 versus 6.5 days (P<0.05) after
      the regimens arresting and lasting 6 versus 10 days (P>0.05). Fludarabine regimen
      had less non-haematological toxic effect than that of VM. CONCLUSION: Compared
      with VM, Fludarabine regimen was a very effective alternative treatment for CR
      induction in adult patients with refractory and relapsed ALL and low toxicity.

PMID- 16086051
TI  - [Repairing brachial plexus root avulsion by nerve transfer].
AB  - OBJECTIVE: To summarize the experience of surgical treatment of brachial plexus
      root avulsion and to discuss the operations for different of types brachial
      plexus root avulsion. METHODS: We enrolled 18 cases of brachial plexus root
      avulsion with different surgical treatment by nerve transfer from October, 1998
      to September, 2002. The follow-up time between 2 years 2 months to 5 years 8
      months, the mean time being 3 years 10 months. RESULTS: The 18 patients were
      followed up more than 2 years. Of the 16 patients who lost shoulder abduction 11
      had recovered to more than grade 3 strength of supraspinatus muscle; 4 had
      recovered to more than grade 3 strength of deltoid muscle. Of the 16 patients who
      lost elbow flexor function 14 had recovered to more than grade 3 strength of
      biceps muscle. Of the 6 patients who lost wrist and finger flexion, 2 had
      recovered to more than grade 3 strength in flexion of wrist and fingers. Of the 4
      patients who lost radial nerve function, 3 had recovered to more than grade 3
      strength of extend elbow and finger. All of them had recovered grade 3 strength
      of extend wrist. CONCLUSION: Accurate diagnosis, early operation and refine
      manipulation are key factors for functional recovery in transferring nerve
      treatment for brachial plexus root avulsion. Different methods should be selected
      according to the types of brachial plexus avulsion. All injured nerves should be
      repaired for young patients.

PMID- 16086052
TI  - [Protein expression profilings of polycystic ovary syndrome].
AB  - OBJECTIVE: To screen out serum protein profiling of polycystic ovary
      syndrome(PCOS) by surface-enhanced laser desorption/ionization time of flight
      mass spectrometry (SELDI-TOF MS) for discovering the discriminatory proteins.
      METHODS: Thirty one women with PCOS and thirty healthy women were detected by
      Weak Cation Exchange(WCX2)chip. ProteinChip reader and Biomarker Wizard software
      from Ciphergen Inc were combined with a bioinformatics method (support vector
      machines, SVM ) to analyze protein fingerprinting. RESULTS: There were 4 proteins
      which were obviously different between the PCOS group and the control. Three of
      them were up-regulated, and one down-regulated. To set up a analysis model by SVM
      using the 4 proteins could successfully distinguish between PCOS and the normal
      control. The corresponding sensitivity, specificity and positive predict value
      were 86.7%, 83.3%, 87.2%, respectively. CONCLUSION: Using ProteinChip technology
      can screen out serum discriminatory proteins quickly and efficiently. Combined
      with SVM, an optimal fingerprinting model has been set up, which can easily
      predict PCOS. In disease state of PCOS, there are significant variations which
      consist of four proteins. To investigate those four discriminatory proteins,
      especially the protein m/z 6 628 may be of benefit to pathogenic study and the
      development of biomarkers for PCOS.

PMID- 16086053
TI  - [Application of two dimensional electrophoresis,western blot and mass spectrum to
      screen markers of endometriosis].
AB  - OBJECTIVE: To find out markers of endometriosis. METHODS: The two dimensional gel
      images of proteins extracted from eutopic endometrium from endometriosis patients
      and controls were analyzed by software Phoretix 2D,and the proteins expressed
      differently were identified primarily by query of data base. The proteins
      extracted from ectopic endometrium of ovarian endometriosis were transferred from
      two dimensional gel onto nitrocellulose membranes, followed by incubation with
      sera from women with and without endometriosis. Analyzed by MALDI-TOF-MS, the
      proteins hybridized differently were identified through their Peptide Mass
      Footprints. RESULTS: Having compared the reproducible two dimensional gel images
      of proteins from eutopic endometrium of women with and without endometriosis,we
      obtained 11 proteins expressed differently. Through Western Blot technique,we
      found three proteins hybridized differently which were identified as vimentin,
      beta-actin and ATP synthase beta subunit respectively. CONCLUSION: The protein
      expression spectra of eutopic endometrium from patients with endometriosis are
      significantly different from those of the controls, and the anti-endometrial
      autoantibodies against vimentin, beta-actin and ATP synthase beta subunit may be
      induced.

PMID- 16086054
TI  - [The effects of sulindac on the pathology of colorectal remnant polyps of
      familial adenomatous polyposis (FAP) patients].
AB  - OBJECTIVE: To evaluate the long-term effectiveness of sulindac on the pathology
      of colorectal adenomas of familial adenomatous polyposis (FAP) patients. METHODS:
      FAP patients were treated with sulindac 400 mg per day. The change of colorectal
      polyps was assessed every 3 months in the first year. After the significant
      regression of colorectal polyps was achieved, sulindac was used to maintain the
      effects. The patients received colonoscopy examination regularly. Biopsies of
      remnant polyps and other lesions were obtained. The type and dysplasia grade of
      biopsies were evaluated and compared with baseline. RESULTS: Before the study,
      90.8% of adenoma biopsies were tubular, while 9.2% was tubulovillous adenoma. The
      dysplasia of grades I, II and III were 42.1%, 45.6% and 12.3%, respectively.
      After sulindac treatment, 99.8% of adenoma biopsies were tubular, while 0.2%
      tubulovillous adenoma. There was significant difference compared with baseline
      (P<0.01). The dysplasia of grades I, II and III were 55.8%, 41.8% and 2.4%
      respectively, which had significant difference with baseline (P<0.01). Minor flat
      elevation and erythema were found during the treatment, in which approximately
      65% was adenoma. CONCLUSION: Long-term use of sulindac seems to be effective in
      reducing dysplasia grade and tubulovillous adenoma of retained colorectal adenoma
      of FAP patients. Minor flat elevation and erythema may be the lesions appearing
      during the regression of adenoma.

PMID- 16086055
TI  - [Anti-endothelial cell antibodies(AECA) are associated with disease activity of
      propylthiouracil induced antineutrophil cytoplasmic antibody (ANCA) positive
      vasculitis].
AB  - OBJECTIVE: To investigate the prevalence of anti-endothelial cell
      antibodies(AECA) and its possible role in the pathogenesis of propylthiouracil
      (PTU) induced ANCA positive vasculitis. METHODS: Sera from 11 patients with PTU
      induced ANCA positive vasculitis and 10 patients with PTU induced ANCA but
      without clinical vasculitis were studied. Soluble proteins from in vitro cultured
      human umbilical vein endothelial cells were used as antigens and immunoblotting
      technique was performed to identify the specific target antigens. RESULTS: In
      patients with PTU induced ANCA positive vasculitis group, 10 of the 11 patients
      in active phase were AECA positive and 7 of the 10 patients turned to negative in
      remission. AECA consisted of a group of heterogeneous antibodies. In patients
      with ANCA positive but without vasculitis, none was AECA positive. CONCLUSION:
      AECAs recognizing a variety of antigens could be found in sera from patients with
      PTU induced ANCA positive vasculitis and they had a much closer association with
      vasculitic disease activity compared with ANCA.

PMID- 16086056
TI  - [Hypoxia stimulates expression of connective tissue growth factor through p38
      signaling pathway in human renal interstitial fibroblasts].
AB  - OBJECTIVE: To assess the expression of connective tissue growth factor (CTGF),
      and relevant mechanism for the regulation of CTGF expression by hypoxia in human
      renal interstitial fibroblast. METHODS: A human renal interstitial fibroblast
      cell line TK173 was treated under hypoxia (1% O(2)) or nomoxia (21% O(2))
      condition. The expressions of HIF1-alpha, hypoxia marker protein, and CTGF
      protein were analyzed by Western blotting. RT-PCR was carried out to measure the
      levels of CTGF mRNA. The activations of MAPKs (ERK, JNK, p38) signaling pathways
      were assessed at different time points (30 min, 1 h, 6 h, and 12 h ), and the
      changes of CTGF expression were detected after the inhibitors of activation of
      MAPKs were applied, respectively. RESULTS: The expression of HIF-1alpha protein
      appeared in cells under hypoxia for 6 h. The expressions of CTGF protein were up
      regulated in TK173 cells under hypoxia for 12 h, reached the peak levels in 2
      folds of normoxia group cells for 24 h, and return to the levels of control cells
      by 48 h. The levels of CTGF mRNA were elevated in cells under hypoxia for 1 h,
      significantly increased at 6 h (6.6+/-1.0, P=0.000 2), and returned to the levels
      of normoxia group cells by 24 h. Activations of ERK1/2, JNK and p38 were seen in
      hypoxic cells. Activation of ERK1/2 and JNK were occurred as early as at 10 min,
      and reached the peak levels at 1 h, while the peak levels of activated JNK were
      seen at 30 min, then the levels of activated ERK1/2, p38, and JNK were all
      declined at 6 h, back to the baseline levels at 12 h. Blockade of ERK activation
      with PD98059, and blockade of JNK activation with SP600125 did not suppress
      hypoxia-induced expression of CTGF protein, whereas blockade of p38 MARK
      activation with SB203580 abolished hypoxia-induced expressions of CTGF protein
      and CTGF mRNA. CONCLUSION: Hypoxia could stimulate the expression of CTGF in
      human renal interstitial fibroblast through the activation of p38 MARK signaling
      pathway.

PMID- 16086057
TI  - [Effects of low molecular weight heparin on vascular endothelial growth factor
      expression of early diabetic nephropathy].
AB  - OBJECTIVE: To investigate the effects of low molecular weight heparin (LMWH) on
      vascular endothelial growth factor (VEGF) expression of early diabetic
      nephropathy. METHODS: Ninety-five male SD rats were randomly divided into three
      groups: normal control rats, STZ-induced diabetic rats and diabetic rats treated
      with LMWH. The renal tissues were subjected to immunohistochemical staining after
      1, 2, 4, 6, and 8 weeks' treatment respectively to quantify the VEGF expression.
      RESULTS: Immunohistochemical staining demonstrated an increasing in VEGF positive
      cells in diabetic rats. It was found that there were significant differences in
      VEGF staining intensity between diabetic rats and normal control rats and between
      LMWH treated rats and untreated diabetic rats after two weeks treatment.
      CONCLUSION: The inhibition of VEGF expression may be one of the mechanisms of
      LMWH's renal protective effects on early diabetic nephropathy.

PMID- 16086058
TI  - [Hypoxia/reoxygenation induced endoplasmic reticulum stress in cultured neonatal
      rat cardiomyocyte].
AB  - OBJECTIVE: To investigate the effect of hypoxia/reoxygenation on endoplasmic
      reticulum stress in cultured neonatal rat cardiomyocytes. METHODS: Neonatal rat
      cardiac myocytes in primary culture were exposed to hypoxia for 5.5 hours and
      subsequently reoxygenation for 2-24 hours. Western blot and RT-PCR were applied
      to monitor the expression change of GRP78 (glucose regulated protein 78). 2-deoxy
      D-glucose (2-DG) was the positive control of this study. Then Western blot and RT
      PCR were used to examine the expression of GRP78. RESULTS: Cell viability was
      decreased obviously after hypoxia/reoxygenation. Compared with untreated cells,
      the GRP78 content of the cells had increased significantly in the
      hypoxia/reoxygenation cells. The level of GRP78 protein and mRNA elevated from
      the points of 2 hours to 24 hours after reoxygenation, and increased most
      obviously at the point of 4 hours after reoxygenation. (4 hours: protein level
      142% of the control, mRNA level 200%). 2-DG could induce the increasing
      expression of GRP78 in a concentration-dependent manner from 10-50 mmol/L.
      CONCLUSION: Hypoxia/reperfusion can induce endoplasmic reticulum stress in rat
      cardiomyocytes.

PMID- 16086059
TI  - [Roles of endogenous carbon monoxide in vasorelaxation disorder of femoral artery
      in diabetic rats].
AB  - OBJECTIVE: To explore the effects of CO on femoral vasorelaxation in diabetic
      rats. METHODS: Using isolated vascular ring tension detecting technique,
      cumulative relaxation responses of femoral arteries to 10(-8) - 10(-4) mol/L
      acetylcholine (ACh) were measured. The content of COHb in blood was detected.
      RESULTS: Diabetic animals expressed lower weight [(249.38+/-7.58) g] than control
      rats [(345.83+/-12.14) g , P<0.01]. The blood sugar levels in diabetic rats
      [(20.28+/-0.35) mmol/L] were significantly higher than that in control rats
      [(5.56+/-0.19) mmol/L]. In addition,diabetic animals demonstrated elevated blood
      pressure [(118.75+/-8.33) mm Hg] after 4 weeks, (132.43+/-10.98) mm Hg after 8
      weeks, (139.0+/-10.41) mm Hg after 12 weeks compared with control (108.43+/-4.18)
      mm Hg, P<0.01, 1 mm Hg=0.133 kPa] in a time-dependent manner. The COHb content in
      the blood was decreased in 4 weeks [(1.50%+/-0.21%) vs (2.50%+/-0.61%)], and
      restored to normal in 8 weeks and 12 weeks in diabetic rats. The dose cumulative
      vasorelaxation-response to ACh in diabetic rats was diminished (63.46%+/-2.48%
      after 4 weeks; 69.76%+/-7.61% after 8 weeks; 49.37%+/-4.74% after 12 weeks
      compared with control 96.81%+/-3.15%). Treatment with hemin did not affect
      weight, blood sugar and blood pressure in diabetic rats, markedly increased the
      COHb content in the blood (3.20%+/-0.73%, P<0.01) and improved the vasorelaxation
      disturbance of femoral arteries (69.76%+/-7.60%, P<0.01) in diabetic rats. While
      administration with ZnPP-IX could inhibit the production of COHb (0.93%+/-0.35%),
      and worse the hypertension [(130.84+/- 8.56) mm Hg] and aggravate the
      vasorelaxation disturbance (37.70%+/-5.65%) vs diabetes (63.46%+/-2.48%) in
      diabetic rats. CONCLUSION: The results suggested that the decrease of blood CO in
      early stage of diabetic rats were related to the vasorelaxation disorder of
      femoral arteries, and that lead to hypertension in diabetic rats,which may be one
      of the important mechanisms of diabetes company hypertension.

PMID- 16086060
TI  - [Changes of leukotriene B4 in chronic obstructive pulmonary disease and effects
      of theophylline on leukotriene B4].
AB  - OBJECTIVE: To investigate the changes of leukotriene B4 (LTB4) in both the
      airways and the blood circulation in an animal model of chronic obstructive
      pulmonary disease (COPD) and the effects of theophylline on LTB4. METHODS: Thirty
      two male Wistar rats were divided into four groups by random number meter: Group
      A (normal controls), group B (COPD), group C (smoking+low dose theophylline), and
      group D (smoking+high dose theophylline ), with 8 rats in each group. Pulmonary
      functions of the rats were assessed, and pathological changes of airways were
      scored. Cell counts and cell differentiation in bronchoalveolar lavage fluid
      (BALF) were also performed. Concentrations of IL-8 and LTB4 in BALF, plasma and
      lung tissue were measured by enzyme-linked immunosorbent assay (ELISA) and enzyme
      immunoassay (EIA). RESULTS: LTB4 concentrations in BALF of COPD rats increased
      significantly as compared with the normal controls, and positively correlated
      with the percentage of neutrophil and IL-8 in BALF (r=0.794, 0.863; P=0.007,
      0.012), and negatively correlated with peak expiratory flow (PEF) (r=-0.718,
      P=0.028). Positive correlations were also found between levels of LTB4 in BALF
      and the scores of inflammatory cell infiltration of COPD rats (r=0.836, P=0.036).
      Treatment with theophylline decreased the percentage of neutrophil and the
      concentrations of LTB4 in BALF of the COPD rats, attenuated the pathological
      changes of small airways, such as airway occlusion, goblet-cell metaplasia,
      inflammatory cell infiltration, and fibrosis and smooth muscle proliferation. The
      effect was more significant on goblet-cell metaplasia and inflammatory cell
      infiltration in the high dose group. However theophylline had little effect on
      PEF. CONCLUSION: Our results suggest that LTB4 is involved in airway inflammation
      in COPD. Theophylline is effective in decreasing the levels of LTB4 in BALF of
      COPD rats, reducing the percentage of neutrophil, and attenuating pathological
      changes of small airways.

PMID- 16086061
TI  - [Inhibitory effects of protease inhibitor on endotoxin-induced acute lung injury
      in rats].
AB  - OBJECTIVE: To investigate the effects of protease inhibitor on lipopolysaccharide
      induced acute lung injury in rats and its possible mechanisms. METHODS: Thirty
      two male Wister rats, weighting 250-270 g, were divided into four groups
      randomly. C, normal controls (n=8); A: acute lung injury group (n=8), receiving
      intravenous endotoxin (lipopolysaccharide O55:B5, LPS 5 mg/kg); V, low-dose group
      (n=8), U, high-dose intervention group (n=8, receiving Ulinastatin 50,000 U/kg
      and 100,000 U/kg respectively and LPS 5 mg/kg). The specimens were collected 2
      hours later, We observed the following changes: blood gas analysis, the lung
      wet/dry weight ratio, the pulmonary vascular permeability, histological
      manifestations, lung tissue myeloperoxidase activity, plasma endothelin-1, lung
      tissue malonaldehyde and conjugated-diene. RESULTS: Compared with Group C, the
      lungs of the rats in Group A had significant hyperemia and spotted hemorrhage.
      The inflammatory granulocyte infiltrating, diffused alveolar septum thickening
      and spotted hemorrhage were observed in pathological examinations. The lung
      wet/dry weight ratio and Evans Blue content (per gram) increased significantly in
      group A [(5.41+/-0.06), (27.64+/-2.48) microg] compared with group C [(4.95+/
      0.08), (12.99+/-2.83) microg], in the intervention groups (U: 5.0+/-0.05, 19.47+/
      2.09; V: 4.98+/-0.06, 21.44+/-3.12) however the difference was not significant
      between the intervention groups; The plasma endothelin-1 and lung tissue
      myeloperoxidase activity increased significantly in group A [(948.23+/-103.45)
      u/g, (152.90+/-8.41) u/g] compared with group C [(729.38+/-88.64) u/g ],
      [(54.62+/-15.49) u/g] but intervention groups [U: (633.27+/-93.27) u/g, (119.40+/
      11.32) u/g; V: (671.87+/-105.45) u/g, (129.55+/-9.57) u/g] decreased
      significantly compared with group A, no significant difference between
      intervention groups; lung tissue Lipid-peroxide (malonaldehyde, MDA and
      conjugated-diene, C-diene) increased significantly in group A [MDA: (73.95+/
      4.62) nmol/g; C-diene: (10.96+/-0.81) nmol/g] compared with group C [MDA:
      (39.65+/-6.21) nmol/g; C-diene: (3.34+/-0.51) nmol/g], intervention groups [U:
      MDA: (51.26+/-5.56) nmol/g, C-diene: (7.59+/-0.84) nmol/g; V: MDA: (59.87+/-4.62)
      nmol/g, C-diene: (8.79+/-0.45) nmol/g] decreased significantly compared with
      group A. MDA decreased significantly in group U compared with group V.
      CONCLUSION: The protease inhibitor, Ulinastatin, may decrease inflammatory
      reaction and further decrease lung damage induced by LPS in rats, all indicating
      protection of protease inhibitor against acute lung injury.

PMID- 16086062
TI  - [Conversion of human umbilical cord blood-derived cells into hepatocyte-like
      cells in a culture system mimicking hepatic injury].
AB  - OBJECTIVE: To explore the effect of the microenvironment induced by damaged mouse
      hepatic cells on the conversion of human umbilical cord blood-derived cells into
      hepatocyte-like cells. METHODS: A hepatic injury-like microenvironment was
      mimicked using carbon tetrachloride damaged mouse hepatic cells, where
      mononuclear cells (MNC) from human umbilical cord blood were cultured in a
      compartment separated by trans-well membrane. Histochemical staining, reversed
      transcription-polymerase chain reaction (RT-PCR) and gene sequencing were
      performed for the information on the conversion of human umbilical cord blood
      MNC. RESULTS: A number of PAS positive stained cells in MNC co-cultured with
      damaged mouse hepatic cells were observed after 72 h. Cells expressing mature
      hepatocyte markers, human albumin (hALB) and human GATA-4 (hGATA-4) mRNA were
      detected by RT-PCR, which was further confirmed with sequencing. Relevant control
      groups, MNC co-cultured with normal mouse hepatic cells and MNC cultured alone
      remained negative. CONCLUSION: The culture system using damaged mouse hepatic
      cells as stimulator could be a potential in vitro system for the conversion of
      human umbilical cord blood-derived cells into hepatocyte-like cells.

PMID- 16086063
TI  - [Organotypic cerebral slice culture and the course of neuronal development in
      it].
AB  - OBJECTIVE: To establish a method of organotypic cerebral culture. So as to pave
      the way for building some neurodegenerative disease models. METHODS: Organotypic
      cerebral cultures were prepared from prefrontal brain of neonatal SD rats. After
      culturing 7 to 14 days, 3 weeks, 4 weeks and 8 weeks, respectively, cerebral
      slices were fixed, dehydrated and sectioned in cryostat. The sections proceeded
      with Nissl staining and neurofilament high molecular weight (NFH)
      immunohistochemical staining. The difference was observed between controls and
      cultured slices using normal rats as controls. RESULTS: Nissl staining showed
      that pyramidal neurons in cultured slices were increased in volume and lightened
      in staining. The delaminating construction was clear from 1 to 4 weeks after
      culturing. In cultured slices, immunohistochemical staining showed that NFH
      positive pyramidal cells appeared on layer V on the tenth day and on both layers
      V and III after culturing 12 days. In the control group, NFH positive pyramidal
      cells appeared on layer V in 5-day-old rats, and appeared on both layers V and
      III in over 3-week-old rats. In cultured cerebral slices, the number of pyramidal
      neurons on layer V in M1 area was invariable from 12 days to 2 months.
      CONCLUSION: Orgaotypic cerebral culture can be used to study postnatal
      development for neocortex and build some in vitro models for neurodegenerative
      diseases.

PMID- 16086064
TI  - [Clinical analysis of primary biliary cirrhosis: a report of 42 cases].
AB  - OBJECTIVE: To study the clinical features of primary biliary cirrhosis (PBC) in
      order to facilitate cognition of the disease. METHODS: Clinical data of 42
      patients clinically and/or histologically diagnosed with PBC were reviewed. Anti
      mitochondrial antibody (AMA) negative/positive patients as well as the patients
      who were/were not associated with Sjogren Syndrome (SS) were compared in terms of
      clinical, biochemical and immunological features. RESULTS: Among the 42 patients,
      78.6% (33/42) of the cases were females; the mean age at diagnosis was (61.1+/
      10.8) years. The most frequent symptoms were fatigue. Serum alkaline phosphatase
      (ALP), gamma-glutamyltranspeptidase (gamma-GT) and total bile acid (TBA) levels
      were markedly elevated in the majority of the patients, whereas ALT and AST
      levels were mildly to moderately elevated. Thirty-one patients had a total
      bilirubin (TBil) level above normal. The levels of TBil and prothrombin time had
      positive correlationship with years of the course (P=0.000, r=0.696; P=0.005,
      r=0.424), whereas serum albumin level had negative correlationship with years of
      the course (P=0.002, r=-0.462). Thirty-seven patients had elevated serum IgM and
      34 patients were AMA/AMA-M(2) positive. AMA negative and AMA positive patients
      were similar in terms of clinical manifestations and liver biochemistries
      findings. Serum IgM and IgA levels were significantly lower, whereas total
      cholesterol level was higher in AMA negative patients when compared with AMA
      positive cases. Fifteen cases were associated with SS, which were similar in
      terms of clinical, biochemical and immunological features when compared with the
      PBC patients were not associated with SS. CONCLUSION: PBC is mostly found in
      middle aged and old women. Elevated serum ALP, TBA and gamma-GT levels together
      with positive AMA/AMA-M(2) can help to diagnose PBC. AMA negative PBC patients
      are characterized by relatively lower serum IgM and IgA levels and higher total
      cholesterol level. PBC patients who are associated with SS have not substantial
      differences in the clinical, biochemical and immunological spectra of the
      disease.

PMID- 16086065
TI  - [In situ hybridization analysis of mRNA expression of 5-Hydroxytryptamine4
      receptor in intestinal mucosa mast cells].
AB  - OBJECTIVE: To verify 5-HT(4) receptor mRNA expression in intestinal mucosa mast
      cells (IMMC). METHODS: IMMC was isolated from the whole intestines of normal rats
      by collagenase digestion and purified by percoll. In situ hybridization was
      performed to detect the expression of 5-HT(4) receptor mRNA in IMMC. RESULTS:
      Evidently positive staining was shown in the cytoplasm of IMMC. CONCLUSION: We
      have verified the expression of 5-HT(4) receptor mRNA in IMMC for the first time
      and provided evidence for further research.

PMID- 16086066
TI  - [Preoperative clinical features and surgical results of congenital cataract].
AB  - OBJECTIVE: To evaluate the relationship between preoperative nystagmus and visual
      outcome of congenital cataract surgery. METHODS: Retrospective review of 81
      patients (84 eyes) who underwent surgery for cataract was conducted,in which 7
      cases of unilateral cataract and 3 of bilateral cataract were associated with
      preoperative nystagmus. All patients lacked other structural ocular defects or
      neurologic abnormalities and were old enough to cooperate with recognition visual
      acuity testing. Outcome parameters studied were best-corrected postoperative
      visual acuity of the eyes. RESULTS: Best corrected postoperative visual acuity of
      the nystagmus eyes was 0.05 or worse in 3 (23%, 3/13), between 0.05 and 0.3 in 9
      (69%, 9/13), and 0.3 or better in 1 (8%, 1/13). Best corrected visual acuity of
      the eyes without nystagmus was 0.05 or worse in 6 (8%), between 0.05 and 0.3 in
      24 (34%), and 0.3 or better in 41 (58%) h. There was a statistical significance
      of preoperative visual acuity compared to postoperative visual acuity in cataract
      with (P= 0.04) or without nystagmus. The great statistical significance was shown
      in the improvement of visual acuity between the patients with nystagmus and
      without nystagmus. CONCLUSION: Preoperative nystagmus in children with cataract
      does not preclude visual improvement, but may predict a poorer visual acuity
      outcome after cataract surgery. In these patients a decision must be made as to
      whether or not surgical intervention for the cataract would be worthwhile at this
      stage.

PMID- 16086067
TI  - [The antitumor activity of Shuang-Xi-Zuo-Wan-1 in C57/BL mice].
AB  - OBJECTIVE: To detect the antitumor activity of Shuang-Xi-Zuo-Wan-1(Eb), a novel
      organoselenium compound, in C57/BL mice transplanted with Lewis lung cancer(LLC).
      METHODS: The LLC transplanted C57/BL mice model was established,and the mice were
      randomly divided into four groups, including high dose Eb group (25.0 mg/kg), low
      dose Eb group (12.5 mg/kg), positive control group (DDP, 2.0 mg/kg) and negative
      control group (solvent). Each group had twelve mice. Intraperitoneal injections
      (ip.) of four pharmaceuticals were performed once a day through the abdominal
      wall separately, from the second to the eighth days after cancer was
      transplanted. On the eleventh day, six mice of each group were killed and the
      influences of Eb on growth speed, size, weight, invasion, inhibitory rate,
      proliferation index and apoptosis rate of LLC were observed and calculated. The
      remaining mice were fed till all of them died naturally and the average survival
      time of each group was calculated. RESULTS: Eb could inhibit the growth and
      infiltration of LLC (the cancer inhibitory rate of high does Eb was 80.31%)
      obviously and prolong the average survival time of these with mice cancer. After
      being given Eb, the nuclear of the cancer cell concentrated and the fission phase
      cells reduced. In addition,the number of apoptosis cancer cells increased.
      CONCLUSION: The novel organoselenium compound Eb has antitumor activity in vivo.
      It can inhibit the growth and infiltration of LLC in mice, and induce the
      apoptosis of cancer cells.

PMID- 16086068
TI  - [Preliminary study of treatment mechanism and stability in deep overbite
      malocclusion with hyperdivergent and hypodivergent skeletal pattern].
AB  - OBJECTIVE: Comparison of structural characteristic changes between deep overbite
      malocclusions with hyper- and hypodivergent skeletal pattern during treatment and
      follow-up stages. To discuss the difference between both in treatment mechanism
      and characteristic of relapse. METHODS: 59 cases out of 162 finished patients
      with deep overbite malocclusion followed for more than 2 years, selected from
      orthodontic clinic in school of stomatology Peking University, were filtered by
      cephalometrics (MP-SN>40 degrees or <29 degrees)and then two groups were formed.
      The hyperdivergent group (MP-SN>40 degrees) comprised 10 cases and the
      hypodivergent group (MP-SN<29 degrees) comprised 9 cases. Measurements and
      statistics were performed upon the two groups. RESULTS: After orthodontic
      treatment, the hyperdivergent group exhibited the extrusions of upper and lower
      molars [U6-PP increased from (10.69+/- 2.10)mm to (12.91+/-2.19)mm; L6-MP
      increased from (17.34+/-2.73)mm to (20.86+/-3.08)mm]. As to the skeletal change,
      a decrease of ANB angle from (5.86+/- 1.34) degrees to (4.62+/-1.67) degrees and
      NA-PA angle from (11.99+/-3.74) degrees to (8.76+/-4.45) degrees reflecting the
      sagittal change tendency from skeletal Class II to Class I. In vertical
      direction, the ratio of Ar-Go/ANS-Me increased from (0.58+/-0.03) to (0.62+/
      0.05). Compared with the hyperdivergent group, the hypodivergent one only showed
      the extrusion of lower molars after treatment. The stability of overbite didn't
      show any statistically significant difference between two groups during the
      follow-up stage. Also in this stage the change of overbite in the hyperdivergent
      group was mainly due to the lingual inclination of upper incisors during the
      treatment stage and in the hypodivergent group it was due to the molar extrusion
      during treatment. CONCLUSION: The ramus showed great potential of growth in the
      hyperdivergent group during the treatment stage, which maintained the inclination
      of mandibular plane. The relapse of overbite was correlated with the changes of
      teeth during the treatment and follow-up stages.

PMID- 16086069
TI  - [Expressions of PDCD5 and p53 in oral leukoplakia and oral squamous cell
      carcinoma].
AB  - OBJECTIVE: To study the relationship of the expressions of new apoptosis-related
      gene PDCD5 and p53 in oral normal mucosa, oral leukoplakia and oral squamous cell
      carcinoma. METHODS: The expressions of PDCD5 and p53 were observed separately in
      17 samples of oral normal mucosa, 60 of oral leukoplakia, and 30 of oral squamous
      cell carcinoma by Immunohistochemical means. RESULTS: PDCD5 positive rate in oral
      normal mucosa was 88.2%, in oral leukoplakia was 63.3%, and in oral squamous cell
      carcinoma was 30%. P53 positive rate in oral normal mucosa was 0, in oral
      leukoplakia was 31.7%, and in oral squamous cell carcinoma was 60%. There was a
      negative relationship between PDCD5 SII and P53 SII in every lesion. CONCLUSION:
      It suggests that both PDCD5 and p53 could be used as molecular markers of
      carcinogenesis for oral epithelium.

PMID- 16086070
TI  - [Effect of TNF-alpha on murine osteoclast differentiation].
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of TNF-alpha
      on osteoclast differentiation in primary murine bone marrow cell culture with and
      without RANKL. METHODS: M-CSF-dependent bone marrow cells were isolated from 5-6
      weeks old mice, and cultured in the presence of M-CSF (25 microg/L) with
      different concentrations of TNF-alpha (0, 1, 10, 100 microg/L) for 5 days, the
      formation of TRAP(+) multinucleated cells was observed. These cells were also
      cultured in the presence of both RANKL (30 microg/L) and M-CSF (25 microg/L) with
      or without 10 microg/L TNF-alpha for 4, 5, 6 and 9 days. The number of TRAP(+)
      multinucleated cells and resorption pits on dentine slices were counted under
      light microscope. RESULTS: In the absence of RANKL, TNF-alpha was unable to
      induce osteoclast formation from murine bone marrow precursors. In the presence
      of RANKL, TNF-alpha augmented osteoclastogenesis and bone resorption, and this
      effect occurred only on the early stage. CONCLUSION: TNF-alpha enhances RANKL
      induced osteoclast formation and function, but cannot substitute for RANKL. TNF
      alpha stimulates osteoclast differentiation, but not survival.

PMID- 16086071
TI  - [Preliminary exploration of the influence factors of degenerate oligonucleotide
      primered PCR of genome DNA].
AB  - OBJECTIVE: To explore the influence factors of the degenerate oligonucleotide
      primered PCR(DOP-PCR). METHODS: Genome DNA template from the mouse single oocyte
      or liver tissue were used to perform DOP-PCR. DOP-PCR was carried out with
      templates of different origin, different gradient dilution, with or without low
      melting point gel purified to wipe off the small fragment that might interfere
      with the following analysis, and then PCR of gene FTCD and CBS were carried out
      to evaluate the influence of these factors on the amplification efficiency and
      specificity. RESULTS: Compared with genome DNA template from mouse liver, the
      template from single oocyte had the same efficiency and specificity but a minor
      yield and different gradient dilution of DNA template had no effect on the
      efficiency and specificity. Furthermore, there was a higher specificity in the
      low melting point gel-purified DOP-PCR product than in untreated ones.
      CONCLUSION: We have got a satisfactory result and increased specificity from DOP
      PCR product purified with the low melting point gel. Single oocyte of mice could
      be used for further investigation of special genes detection by DOP-PCR and of an
      optimization in the yield of the products.

PMID- 16086072
TI  - [Recent advances in the diagnosis and treatment of lysosomal storage diseases].
AB  - Lysosomal storage diseases are a group of genetic disorders that result from the
      defect in lysosomal function. Signs and symptoms are variable, it is difficult to
      diagnose this group of disease merely by the clinical manifestation. The
      diagnosis usually is made by measuring the activity of the corresponding enzyme.
      Gene mutational analysis is useful for the diagnosis of some of the lysosome
      storage diseases. The treatment has focused on the replacement of the defective
      enzyme responsible for the disease and the hematopoietic stem cell
      transplantation. Both of them have achieved exciting outcomes in some of the
      diseases.

PMID- 16086073
TI  - [Progress in National Institutes of Health roadmap initiatives].
AB  - National Institutes of Health (NIH) released the biomedical research project NIH
      Roadmap Initiatives, including 3 themes, new pathways to discovery, research
      teams of the future, and re-engineering the clinical research enterprise. The
      purpose of the project is to catalyze to transform our new scientific knowledge
      into tangible benefits for people. Now, mostly of the project have begin to carry
      into practice.

PMID- 16086074
TI  - Probiotics, prebiotics and antioxidants as functional foods.
AB  - The term "functional foods" comprises some bacterial strains and products of
      plant and animal origin containing physiologically active compounds beneficial
      for human health and reducing the risk of chronic diseases. Among the best known
      functional compounds probiotics, prebiotics and natural antioxidants should be
      given as examples. These substances can be obtained by biotechnological methods
      and by extraction from plant or animal tissues.

PMID- 16086075
TI  - Molecular modelling of membrane activity of amphotericin B, a polyene macrolide
      antifungal antibiotic.
AB  - Amphotericin B (AmB) is a well known polyene macrolide antibiotic used to treat
      systemic fungal infections. Despite its toxicity AmB is still regarded as a life
      saving drug. The lack of adequate knowledge of the AmB mechanism of action is a
      serious obstacle to efficient development of new less toxic derivatives.
      Complementary to various experimental approaches, computational chemistry methods
      were used to study AmB mechanism of action. A programme lasting for a decade,
      that was run by our group covered studies of: i) molecular properties of AmB and
      its membrane targets, ii) structure and properties of AmB membrane channels, and
      iii) interaction of AmB with the membrane.

PMID- 16086076
TI  - Kinetic analysis of the transient phase and steady state of open multicyclic
      enzyme cascades.
AB  - This paper presents a kinetic analysis of the whole reaction course, i.e. of both
      the transient phase and the steady state, of open multicyclic enzyme cascade
      systems. Equations for fractional modifications are obtained which are valid for
      the whole reaction course. The steady state expressions for the fractional
      modifications were derived from the latter equations since they are not
      restricted to the condition of rapid equilibrium. Finally, the validity of our
      results is discussed and tested by numerical integration. Apart from the
      intrinsic value of knowing the kinetic behaviour of any of the species involved
      in any open multicyclic enzyme cascade, the kinetic analysis presented here can
      be the basis of future contributions concerning open multicyclic enzyme cascades
      which require the knowledge of their time course equations (e.g. evaluation of
      the time needed to reach the steady state, suggestion of kinetic data analysis,
      etc.), analogous to those already carried out for open bicyclic cascades.

PMID- 16086077
TI  - A subset of the follicular variant of papillary thyroid carcinoma harbors the
      PAX8-PPARgamma translocation.
AB  - The occurrence of the PAX8-PPARgamma fusion gene is thought to be restricted to
      follicular tumors (adenomas and carcinomas) of the thyroid (FTA and FTC). Using
      interphase fluorescent in situ hybridization (FISH), together with recombinant
      tissue-type polymerase chain reaction (RT-PCR) and immunohistochemistry, we
      detected the PAX8-PPARgamma translocation in 4 of 8 cases of the follicular
      variant of papillary thyroid carcinoma (FVPTC) exclusively or almost exclusively
      (>95%) composed of follicles. The 4 tumors with the translocation were larger and
      apparently more invasive than the remaining tumors, but the series is too small
      to allow a statistically meaningful comparison of the data. Our findings show
      that follicular thyroid carcinoma (PTC) may also harbor the PAX8-PPARgamma fusion
      gene and indicate that a subset of FVPTC shares some molecular features of FTA
      and FTC.

PMID- 16086078
TI  - Simultaneous bilateral breast carcinomas: a category with frequent coexpression
      of HER-2 and ER-alpha, high Ki-67 and bcl-2, and low p53.
AB  - The aim of this study was to evaluate clinicopathological characteristics and
      immunophenotypes of simultaneous bilateral adenocarcinomas of the breast and
      their axillary metastases. Immunohistochemical analysis and in situ hybridization
      were performed using formalin-fixed/paraffin-embedded tissues. In total, 15
      primary and 9 metastatic tumors from 8 patients were evaluated. The expression of
      estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), Ki 67, p53, bcl
      2, and bax were evaluated by immunohistochemistry. Her2 gene amplification was
      evaluated by chromogenic in situ hybridization (CISH). Four patients were younger
      that 40 years of age (mean 47 years). Six patients had pleomorphic lobular
      carcinoma in 1 breast. Four of these had invasive ductal carcinoma in the
      contralateral breast. One patient had atypical medullary carcinoma in both
      breasts and 1 patient had atypical medullary carcinoma in 1 breast and
      pleomorphic lobular carcinoma in the other. The phenotype of the primary tumors
      and corresponding metastatic tumors was similar for the expression of ER-alpha
      (p=0.001), PR (p=0.03), and HER-2 (p=0.018). While strong coexpression of HER-2
      and ER-alpha is exceptional in hereditary breast carcinoma and sporadic breast
      carcinoma, 6/8 (75%) patients in this study had tumors with strong coexpression
      of HER-2 and ER-alpha. P53 protein expression was found in only 2/15 (13%)
      primary tumors, which is in contrast to BRCA1-related hereditary bilateral breast
      carcinomas, which often express p53 protein. Most of the patients presented with
      axillary metastases and had very aggressive course. Characteristically, the
      tumors showed high levels of expression of ER-alpha and Her2 amplification, were
      bcl-2 positive, and had high Ki-67 fraction. However, in patients with atypical
      medullary carcinoma there was no expression of ER-alpha or amplification of Her
      2.

PMID- 16086079
TI  - The fast-track biopsy (FTB): description of a rapid histology and
      immunohistochemistry method for evaluation of preoperative breast core biopsies.
AB  - Thirty-six core breast biopsies from 32 patients were paraffin embedded by use of
      an automated microwave processor. In addition, a quick immunohistochemical method
      was used in selected cases. The quality of the hematoxylin and eosin (H&E) slides
      was very satisfactory, as were also the immunohistochemical stains for ER, PR,
      and Ki67 when compared to those obtained with the use of a conventional automated
      immunostainer. The time required to process the tissue to the final H&E stage
      averaged 2 hours 52 minutes, and the immunohistochemical method required 90 to
      100 minutes. This procedure, which we named "fast-track biopsy'' (FTB), is quick
      enough to be competitive with FNAC (fine-needle aspiration biopsy) in terms of
      turnaround-times. The superiority of core biopsy over FNA in terms of the
      morphologic information provided is widely acknowledged, the only major argument
      currently mentioned in favor of FNAC being the shorter duration of the procedure.
      With the advent of FTB, it would appear that even this last remaining advantage
      has been erased.

PMID- 16086080
TI  - Identification of mislabeled specimen by molecular methods: case report and
      review.
AB  - Specimen misidentification is a common cause of errors in surgical pathology. We
      report a case where bone-marrow biopsies from patients of different genders were
      mislabeled and molecular methods were applied to resolve the identity. A short
      tandem repeat (STR)-polymerase chain reaction-based assay, commonly used in
      paternity testing, was employed in an attempt to assign the correct identity to
      the specimens. However, the specimens had been processed by decalcification and
      the DNA yield was poor. One of the markers in the assay is the non-STR amelogenin
      locus that distinguishes the X and Y chromosomes. This amelogenin marker results
      in a product of low molecular weight, enabling unequivocal resolution of identity
      despite a poor DNA yield. The prevalence of errors in pathology due to specimen
      misidentifications is reviewed.

PMID- 16086081
TI  - Comparative histologic assessment of proctocolectomy specimens from Japanese and
      American patients with ulcerative colitis with or without dysplasia.
AB  - There have been no reports of histologic differences in ulcerative colitis (UC)
      between Japanese and American patients. We therefore compared histology in
      proctocolectomy resection specimens between Japanese patients with UC (19 cases
      with and 21 without dysplasia) at the Kitasato University East Hospital and
      American patients with UC (21 cases with and 24 without dysplasia) at the
      University of Washington Medical Center. In cases of UC with, but not without
      dysplasia, cryptitis (p = 0.010) and epithelial apoptosis (p < 0.001) in the
      nondysplastic mucosa were more frequently observed in Japanese than in American
      cases, whereas lamina propria fibrosis was more prominent in American
      counterparts (p = 0.008). In patients with UC with dysplasia, the duration of
      disease was significantly longer in American than in Japanese patients (median,
      17 vs 14 years, respectively; p = 0.038). This might, in part, explain the
      histologic variation. Another possibility for the differences is that the
      preoperative medications may have differed in the populations.

PMID- 16086082
TI  - Reactive lymphoid hyperplasia of the lymph nodes with giant follicles: a
      clinicopathologic study of 14 Japanese cases, with special reference to Epstein
      Barr virus infection.
AB  - To clarify the clinicopathologic and immunohistochemical features of reactive
      lymphoid hyperplasia with giant follicles (RHGF) among Japanese, 14 patients were
      studied. The subjects consisted of 9 males and 5 females, ranging in age from 9
      to 61 years, with a mean age of 30 years and a median age of 24 years. None of
      the patients exhibited systemic symptoms. The affected lymph nodes were located
      in the head and neck area except in 1 case. At the time of lymph node biopsy, 1
      patient was diagnosed as having acute infectious mononucleosis (IM) and 2
      patients had a recent history of acute IM. One each with myelogenous leukemia or
      diffuse large B-cell lymphoma had a history of peripheral blood stem cell
      transplantation. There were no recurrences during follow-up periods ranging from
      3 to 50 months. Histologically, 14 lesions were characterized by numerous
      enlarged, coalescing lymphoid follicles with distortion rather than effacement of
      the lymph node architecture. By in situ hybridization, Epstein-Barr virus (EBV)
      genomes were demonstrated in 5 (36%) of 14 cases. The present study indicates
      that a portion of RHGF appears to represent a histologic finding of acute IM.
      Moreover, as previously stated, RHGF should be differentiated from follicular
      lymphoma, particularly the floral variant.

PMID- 16086083
TI  - Distribution of Epstein-Barr virus in systemic rheumatic disease (rheumatoid
      arthritis, systemic lupus erythematosus, dermatomyositis) with associated
      lymphadenopathy: a study of 49 cases.
AB  - Among systemic rheumatic diseases (SRDs), lymphadenopathy is frequently found in
      patients with rheumatoid arthritis (RA) and systemic lupus erythematous (SLE).
      Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) may
      occur in patients following methotrexate therapy for RA and dermatomyositis (DM).
      However, little is known about the distribution of EBV in reactive LPDs in
      patients with SRDs who had no history of methotrexate therapy. We analyzed 49
      such patients (SLE=25, RA=23, DM=1) for the presence and distribution of EBV+
      cells using Epstein-Barr virus (EBV)-encoded small RNA (EBER) specific in situ
      hybridization. A positive signal for EBERs was identified in 9 (SLE=5, RA=4)
      (18%) of 49 cases, and 3 main distribution patterns of EBER+cells could be
      delineated: pattern A, more than 500 EBER-positive cells were located in the
      germinal centers as well as interfollicular area (SLE=2); pattern B, EBER + cells
      were located in a few germinal centers (RA=2); and pattern C, up to 100 EBER+
      cells were located in the interfollicular area (SLE=3, RA=2). Recent EBV
      infection may be a cause of lymph node lesion in only 2 cases of patients with
      pattern A. However, the pathognomonic significance of pattern B and pattern C
      EBER + cell distribution patterns still remains unclear. Our study indicates that
      the underlying immune deficits of patients with SRDs may also play an important
      role in the development of EBV-associated LPDs in SRDs, as previously suggested
      by several authors.

PMID- 16086084
TI  - Images in pathology. Melanotic oncocytic metaplasia of the nasopharynx.

PMID- 16086085
TI  - Images in pathology. "Digital'' lung metastasis of a renal oncocytoma.

PMID- 16086086
TI  - Regressed cutaneous malignant melanoma mimicking lymphoma: a potential diagnostic
      pitfall.
AB  - We report 2 cases of partially regressed malignant melanoma in which the brisk
      lymphocytic response closely resembled mycosis fungoides in 1 case and nodular
      sclerosing Hodgkin lymphoma in the other. Striking epidermotropism was present in
      both cases. The lymphocytes were predominantly of T8 cytotoxic subtype, and
      oligoclonal T-cell expansion was detected in 1 of the cases. The scanty residual
      melanoma cells were highlighted with HMB45 and S100 protein. We highlight the
      features of regression in melanoma that may lead to an erroneous diagnosis of
      lymphoma and discuss the finding of oligoclonal T-cell expansion in regressed
      melanocytic lesions.

PMID- 16086087
TI  - Rosai-Dorfman disease: successful long-term results by combination chemotherapy
      with prednisone, 6-mercaptopurine, methotrexate, and vinblastine: a case report.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML), also known as Rosai
      Dorfman disease (RDD), is a rare clinicopathologic entity of unknown etiology.
      The majority of patients do not require treatment, demonstrating spontaneous
      resolution or stable disease. However, in some cases the disorder runs a
      progressive course and/or threatens vital structures and functions, which
      dictates some form of intervention. It is not clear what constitutes the best
      approach for those cases. We report on a girl with an extensive and progressive
      form of the disease who was cured with combination chemotherapy, showing no
      evidence of recurrence after a follow-up of 5.5 years.

PMID- 16086088
TI  - Granular cell tumor of the thyroid: a case report.
AB  - We report a rare case of granular cell tumor (GCT) arising within the thyroid
      parenchyma. The differential diagnosis of GCT in thyroid includes all
      oncocytic/Hurthle cell lesions of the thyroid, medullary carcinoma and
      metastasis. The classic histomorphologic features and immunohistochemistry are
      helpful in arriving at the correct diagnosis.

PMID- 16086089
TI  - Pigmented mucoepidermoid carcinoma of the oral cavity: a case report.
AB  - Melanocytes are normally present in the oral mucosa, but unlike the skin,
      melanocytic colonization and pigmentation of nonmelanocytic tumors rarely occur.
      A case of pigmented mucoepidermoid carcinoma (MEC) in a 36-year-old woman is
      reported. On H&E-stained sections, brownish granules were seen in intermediate
      and epidermoid neoplastic elements and in elongated or dendritic cells showing
      histologic and immunohistochemical features of melanocytes. Ultrastructurally
      numerous epithelial cells contained large aggregates of melanin granules, a
      feature suggestive of phagocytosis. In addition small individual melanin granules
      were observed at the external border of the epithelial cell membrane. These
      features suggest that melanocytes colonized the MEC and that neoplastic cells may
      phagocytose the granules, similarly to what occurs with epidermal melanocytes.
      The phenomenon of melanocyte colonization of nonmelanocytic tumors should be
      taken into consideration in dealing with pigmented lesions of the oral cavity.

PMID- 16086090
TI  - Mediastinal germ cell tumor associated with histiocytic sarcoma of spleen: case
      report of an unusual association.
AB  - We present an unusual association of mediastinal germ cell tumor containing
      seminoma and angiosarcoma components and splenic histiocytic sarcoma. A 15-year
      old boy presented with chest pain. Histopathologically, an anterior mediastinal
      mass contained typical seminoma, immature teratoma, embryonal carcinoma,
      angiosarcoma, yolk sac tumor, and polyembryoma. An abdominal ultrasonogram
      revealed a huge splenomegaly with multiple ill-defined low echogenic nodules, 1
      month after the second cycle of chemotherapy. Histopathologically, large, round
      to-oval tumor cells with abundant eosinophilic cytoplasm often contained
      eccentrically placed nuclei with vesicular chromatin and an irregular nuclear
      membrane. The tumor cells were immunoreactive for CD68, CD31, and CD4. The
      cytogenetic results showed deletion of the long arm of chromosome 5 and trisomy
      8. This lesion might have been on the pathway of multistep tumorigenesis toward a
      final leukemia.

PMID- 16086091
TI  - Primary angiolipoma of the thyroid gland: a case report.
AB  - We report a case of an angiolipoma involving the thyroid gland of a 74-year-old
      woman. The patient presented with a multinodular goiter that was surgically
      removed. Gross examination of the specimen revealed an intrathyroidal well
      circumscribed nodule that microscopically showed the typical features of an
      angiolipoma. There was no evidence of extrathyroidal extension, necrosis, or
      atypia. To our knowledge, this is the first reported case of a primary
      angiolipoma of the thyroid gland.

PMID- 16086093
TI  - Elevated carbon dioxide increases nectar production in Epilobium angustifolium L.
AB  - Effects of elevated CO2 and nutrient availability on nectar production and onset
      of flowering in five different seed families (genotypes) of Epilobium
      angustifolium were investigated in a greenhouse experiment. Elevated CO2
      significantly increased nectar production per day (+51%, p < 0.01), total sugar
      per flower (+41%, p < 0.05), amino acid concentration (+65%, p < 0.05) and total
      amino acids per flower (+192%, p < 0.001). All other parameters tested, i.e.,
      nectar sugar concentration, proportion of glucose/fructose and proportion of
      sucrose/(glucose + fructose), were not significantly affected by elevated CO2
      and/or fertilization. However, elevated CO2 caused a marginally significant trend
      for earlier flowering in highly fertilized plants. No significant family x CO2
      interaction was found in any of the tested parameters, but the response in nectar
      production varied considerably among seed families (+10 to +104%) and was
      significantly positive in two of the five seed families investigated. Our results
      are not consistent with earlier studies on effects of elevated CO2 on nectar
      production and flowering phenology in other plant species. It seems, on the other
      hand, that CO2 effects on nectar production are specific to species and genotype.
      Hence, no general conclusions about effects of elevated CO2 on these floral
      traits can be drawn at present, but it must be cautioned that elevated CO2 might
      not only increase floral rewards as in E. angustifolium, but might also lead to
      shifts or even disruptions in fine-tuned plant-pollinator interactions.

PMID- 16086094
TI  - Basic fibroblast growth factor improves trabecular bone connectivity and bone
      strength in the lumbar vertebral body of osteopenic rats.
AB  - Recently, basic fibroblast growth factor (bFGF) has been found to increase
      trabecular bone mass and connectivity in the proximal tibial metaphyses (PTM) in
      osteopenic rats. The purpose of this study was to determine the bone anabolic
      effects of bFGF in the lumbar vertebral body (LVB), a less loaded skeletal site
      with a lower rate of bone turnover than the PTM. Six-month old female Sprague
      Dawley rats were ovariectomized (OVX) or sham-operated and untreated for 8 weeks
      to induce osteopenia. Then group 1 (sham) and group 2 (OVX) were treated
      subcutaneously (s.c.) with vehicle, and OVXed groups 3 and 4 were treated s.c.
      with PTH [hPTH (1-34) at 40 microg/kg, 5x/week] and bFGF (1 mg/kg, 5x/week),
      respectively, for 8 weeks. At sacrifice, the fifth LVB was removed, subjected to
      micro-CT for determination of trabecular bone structure and then processed for
      histomorphometry to assess bone turnover. The sixth LVB was used for mechanical
      compression testing (MTS, Bionix 858). The data were analyzed with the Kruskal
      Wallis test followed by post-hoc testing as needed. After 16 weeks of estrogen
      deficiency, there were significant reductions in vertebral trabecular bone volume
      and trabecular thickness. Treatment with either bFGF or hPTH (1-34) increased
      BV/TV in OVX animals. Human PTH (1-34)-treated animals had significant increases
      in trabecular (48%) and cortical thickness (30%) and bone strength [maximum load
      (53%) and work to failure (175%)] compared to OVX + Vehicle animals. Treatment of
      osteopenic rats with bFGF increased bone volume (15%), trabecular thickness
      (13%), maximum load (45%) and work to failure (140%) compared to OVX + Vehicle
      animals (all P <0.05). Basic FGF increased trabecular bone volume in the lumbar
      vertebral body of osteopenic rats by restoring trabecular number, thickness and
      connectivity density. Also, bFGF improved bone mechanical properties (maximum
      force and work to failure) compared to the OVX + Vehicle group. Therefore,
      increasing the number, thickness and connections of the trabeculae contributes to
      increased bone strength in this small animal model of osteoporosis.

PMID- 16086096
TI  - Interferon-alpha plus capecitabine and thalidomide in patients with metastatic
      renal cell carcinoma: a pilot study.
AB  - PURPOSE: To assess the activity and toxicity of interferon-alpha (IFN-alpha),
      capecitabine, and thalidomide in patients with metastatic renal cell carcinoma
      (MRCC). PATIENTS AND METHODS: Twenty-seven patients were enrolled in a pilot
      study to receive oral capecitabine 1,900 mg/m2/day in 2 daily doses, 2 weeks on,
      l week off; daily subcutaneous IFN-alpha 1 mIU without interruption; and daily
      oral thalidomide 200 mg/day for the first seven days, then escalated to 400
      mg/day without interruption. Dosages were reduced for toxicity as necessary.
      RESULTS: Two patients discontinued treatment during the first week of the study,
      leaving 25 patients evaluable. There were 5 (20%) partial responses (PRs), 1 (4%)
      minor response (MR), 6 (24%) cases of stable disease (SD) > or = 6 months, and 13
      (52%) cases of progressive disease (PD). The interval from first response to
      disease progression varied from 0-23 months: 17 patients progressed in 0-6
      months; 4 progressed in 7-12 months; and 4 progressed in 12-24 months. Median
      survival was > 22 months, 14 months, and 1 month, respectively, for patients with
      PR, SD, and PD. Grade 3/4 toxicities consisted of hand-foot syndrome, neuropathy,
      fatigue, anemia, and deep venous thrombosis were common. CONCLUSION: This study
      demonstrates antitumor activity of combination IFN-alpha/capecitabine/thalidomide
      in MRCC. The 20% PR rate was notable, as the patient population had advanced
      disease and inferior performance status. Treatment was generally well tolerated,
      and further research is warranted to explore the efficacy of this combination for
      treating MRCC.

PMID- 16086097
TI  - Pre-irradiation 9-amino [20s] camptothecin (9-AC) in patients with newly
      diagnosed glioblastoma multiforme.
AB  - PURPOSE: To evaluate the efficacy of 9-amino [20s] camptothecin (9-AC) given
      before radiation therapy to patients with newly diagnosed glioblastoma multiforme
      (GBM). METHODS: Eligible patients had newly diagnosed GBM who had residual
      measurable contrast-enhancing tumor. The trial was a phase 2 trial of 9-AC at
      1100 microg/m2 /24 h infused over 72 h every two weeks for up to six cycles in
      patients with newly diagnosed GBM before radiation therapy. RESULTS: Fourteen
      patients entered the study and all were evaluable. All of the patients had
      progressive disease by imaging criteria after at least two cycles of 9-AC (1
      month). The median overall survival was 7.5 months (range 1.5-18 months). The
      most common adverse event was transient lymphopenia (grade 3-4). One patient
      developed grade 4 neutropenic fever that resolved after three days of diagnosis.
      CONCLUSIONS: 9-AC lacks activity against glioblastoma multiforme (GBM). Further
      studies looking at the efficacy of 9-AC in GBM may be futile.

PMID- 16086098
TI  - Changing distribution of group A rotavirus G-types and genetic analysis of G9
      circulating in Japan.
AB  - A total of 1,797 fecal specimens from infants and children with acute
      gastroenteritis in Japan from July 2000 to June 2003 were tested for group A
      rotavirus by ELISA, RT-PCR, RNA-PAGE and latex agglutination methods. Of these,
      439 were found to be positive for group A rotavirus and this presented 24.4%. In
      2000-2001, G1 was the most prevalent (45.5%) followed by G2 (32.5%), G3 (12.3%),
      G9 (5.9%) and G4 (2.6%). However, G2 was found predominant with 40% in the
      following year (2001-2002). Interestingly, G9 had a rapid increase of infection
      up to 17.8%. In 2002-2003, G3 dominated over other G-types with 34%. Another
      interesting feature of the study was the demonstration of great genetic diversity
      among G9 strains in Japan. Worth of note was the first prevalence pattern of
      rotavirus G-types with an increase of G2, G3 as well as G9 and a decrease of G1
      during the 20 year-survey of rotavirus infection in Japan.

PMID- 16086099
TI  - Infectious bursal disease virus recovery from Vero cells transfected with RNA
      transcripts is enhanced by expression of the structural proteins in trans.
AB  - Positive sense RNA transcripts of infectious bursal disease (IBD) virus genome
      segments A and B have previously been shown to be infectious. In this study we
      demonstrate that recovery of IBD virus from the transfection of Vero cells with
      positive sense RNA transcripts of genome segments A and B was enhanced by
      expression of the viral structural proteins VP2 with VP3 or by expression of
      viral polyprotein VP243 from DNA plasmids in trans. Expression of individual
      viral proteins VP2, VP3, or VP4 alone from DNA plasmids did not enhance IBD virus
      recovery. Earliest virus recovery from transfection of positive sense RNA
      transcripts of genomic segments A and B was at 36 h and mean titers were 10(1.8)
      pfu/ml. IBD virus was recovered 6 hours after transfection in cells concurrently
      expressing either VP2 with VP3 or VP243 and mean titers were 10(8.5) pfu/ml or
      10(9.2) pfu/ml, respectively. Likewise, expression of the viral polyprotein from
      DNA plasmid increased the permissiveness of Vero cells for infection with non
      culture adapted IBD virus. The titer of recovered non-culture adapted virus from
      10(3.3) pfu/ml to 10(10.3) pfu/ml with expression of the viral polyprotein. This
      report is the first to describe a reverse genetics model for IBD virus with high
      efficiency of virus recovery for non-culture adapted strains.

PMID- 16086100
TI  - Characterization of resistance in transgenic Nicotiana benthamiana encoding N
      terminal deletion and assembly mutants of the tobacco etch potyvirus coat
      protein.
AB  - The resistance of transgenic Nicotiana benthamiana plants encoding wild type,
      truncated and point mutants of the tobacco etch virus (TEV) coat protein (CP) was
      analyzed. After R1 plants from 45 transgenic lines were challenged with TEV, six
      percent of the lines exhibited high resistance, 38% exhibited low resistance, and
      the remainder were susceptible. The phenomenon of recovery and delay in symptom
      development was observed in 65% and 56% of the resistant and susceptible lines,
      respectively. Plants containing genes that encode sequences of two assembly
      deficient mutants of TEV-CPDelta1-63 exhibited resistance to infection,
      suggesting that self-assembly of the CP is not responsible for resistance. Highly
      resistant lines accumulated low levels of transgene mRNA and non-detectable
      amounts of protein, and tissues accumulated lower amounts of transgene mRNA
      following recovery than before infection. In addition, co-suppression of
      replication of a recombinant tobamovirus containing the TEV-CPDelta1-63 sequence
      was observed in several lines, suggesting homology-dependent degradation of RNA,
      most likely through induction of post-transcriptional gene silencing. Plants not
      exhibiting high resistance via gene silencing exhibited moderate levels of
      resistance that is attributed to and/or affected by the CP molecule.

PMID- 16086101
TI  - Anaerobic induction of adherence to laminin in Lactobacillus gasseri strains by
      contact with solid surface.
AB  - The effect of growth conditions on adhesion was studied in six species belonging
      to Lactobacillus acidophilus homology groups. Namely, 17 strains including 6
      fresh isolates of L. gasseri from human feces were assessed for their adherence
      to immobilized fibronectin, laminin, and type IV collagen. These extracellular
      matrix proteins were used as a model of damaged intestinal mucosa. When the
      bacteria were grown on MRS agar under anaerobic conditions, all eight L. gasseri
      strains and one L. johnsonii strain showed strong adhesiveness to laminin, but
      not when grown in static MRS broth. A similar pattern was observed in four L.
      gasseri strains in terms of adherence to fibronectin. No L. gasseri or L.
      johnsonii strains exhibited adhesion to type IV collagen under either growth
      condition. Adhesion of L. acidophilus, L. crispatus, L. amylovorus, and L.
      gallinarum was not affected by the growth conditions. Although protease treatment
      of L. gasseri cells abolished the adhesion, periodate oxidation of the cells
      increased it except in one strain. The adherence of L. gasseri cells was
      diminished by periodate and alpha-mannosidase treatments of immobilized laminin.
      The above results suggest that mannose-specific proteinaceous adhesion can be
      induced in L. gasseri by contact with a mucosal surface in the anaerobic
      intestinal lumen.

PMID- 16086102
TI  - Comparison of the antimicrobial adhesion potential of human body fluid
      glycoconjugates using fucose-binding lectin (PA-IIL) of Pseudomonas aeruginosa
      and Ulex europaeus lectin (UEA-I).
AB  - Pseudomonas aeruginosa produces a fucose-binding lectin (PA-IIL) which strongly
      binds to human cells. This lectin was shown to be highly sensitive to inhibition
      by fucose-bearing human milk glycoproteins. Since the glycans of these
      glycoproteins mimic human cell receptors, they may function as decoys in blocking
      lectin-dependent pathogen adhesion to the host cells. Human saliva and seminal
      fluid also contain such compounds, and body fluids of individuals who are
      "secretors" express additional fucosylated (alpha 1,2) residues. The latter are
      selectively detected by Ulex europaeus lectin UEA-I. The aim of the present
      research was to compare the PA-IIL and UEA-I interactions with human salivas and
      seminal fluids of "secretors" and "nonsecretors" with those obtained with the
      respective milks. Using hemagglutination inhibition and Western blot analyses, we
      showed that PA-IIL interactions with the saliva and seminal fluid glycoproteins
      were somewhat weaker than those obtained with the milk and that "nonsecretor"
      body fluids were not less efficient than those of "secretors" in PA-IIL blocking.
      UEA-I, which interacted only with the "secretors" glycoproteins, was most
      sensitive to those of the seminal fluids.

PMID- 16086103
TI  - Berberine inhibits arylamine N-acetyltransferase activity and gene expression in
      Salmonella typhi.
AB  - The effects of berberine on growth, arylamine N-acetyltransferase (NAT) activity,
      and gene expression in Salmonella Typhi (Typhi) were described. The growth
      inhibition of Typhi was determined by measuring absorbance by optical density (OD
      at 650 nm). The NAT activity was determined by measuring the levels of 2
      aminofluorene (AF) and N-acetyl-2-aminofluorene (AAF) by high-performance liquid
      chromatography. The results demonstrated that 24-h berberine treatment decreased
      bacteria growth and amounts of AAF in Typhi. Western blotting and flow cytometry
      were used for examining the levels of NAT after bacteria were cotreated with or
      without various concentrations of berberine, and results indicated that berberine
      decreased the levels of NAT in Typhi. Polymerase chain reaction was used for
      examining the gene expression of NAT (mRNA NAT), and results indicated that
      berberine affects mRNA NAT1 expression in Typhi.

PMID- 16086104
TI  - Unusual accumulation of demethylspheroidene in anaerobic-phototrophic growth of
      crtA-deleted mutants of Rhodovulum sulfidophilum.
AB  - Rhodovulum sulfidophilum produces carotenoids in the spheroidene pathway.
      Spheroidene monooxygenase, CrtA, catalyzes the conversion of spheroidene to
      spheroidenone. crtA-deleted mutants of R. sulfidophilum did not produce
      spheroidenone and demethylspheroidenone. In these mutants, the ratio of
      demethylspheroidene to spheroidene increased with exposure to light. One mutant
      exhibiting a spheroidene-predominant phenotype did not grow under anaerobic-light
      conditions and was devoid of bacteriochlorophyll a, even under semiaerobic-light
      conditions There was no difference in the growth of the mutants under aerobic
      dark conditions. These data suggest that demethylspheroidene is important for
      photosynthesis in R. sulfidophilum.

PMID- 16086105
TI  - Construction, expression, and characterization of a thermostable xylanase.
AB  - A hybrid gene, btx, encoding a thermostable xylanase, Btx, was constructed by
      substituting the 31 N-terminal amino acid residues of the Thermomonospora fusca
      xylanase A (TfxA) for the corresponding region of 22 amino acid residues of the
      Bacillus subtilis xylanase A (BsxA). The btx gene was expressed in Escherichia
      coli BL21. The halo size produced by xylanase Btx on a Remanzol brilliant blue R
      (RBB) xylan plate at 60 degrees C and pH 6.0 was larger than those of BsxA and
      TfxA. The molecular weight of Btx was 22 kDa. Temperature and pH optima for Btx
      were at 50-60 degrees C and 6.0, respectively. Btx showed activity over 80% over
      a pH range of 5.0-9.0, which was wider than that of BsxA, and was also more acid
      resistant than TfxA. Btx exhibited significant thermostability compared with
      BsxA. The results show the importance of the N-terminal sequence of TfxA in
      thermostability.

PMID- 16086106
TI  - MonoADP-ribosylation of the NAD+-dependent alcohol dehydrogenase from Entamoeba
      histolytica.
AB  - The human parasite Entamoeba histolytica is an amitochondrial protozoan whose
      metabolism depends on glucose fermentation. Among the metabolic enzymes
      absolutely required for amoeba growth is the NAD+-dependent alcohol dehydrogenase
      (EhADH2). The polymeric form of EhADH2 was sedimented at 160,000 g, and in this
      fraction we observed [32P]-labeling of a 96-kDa protein under mono-ADP
      ribosylation conditions with [32P]NAD+. The [32P]-labeled protein had the same
      molecular weight as the EhADH2 monomer. Because of the importance of monoADP
      ribosylation in the regulation of many physiological processes, the aim of this
      study was to determine whether EhADH2 is ADP-ribosylated, and what would be the
      consequence of this modification on its alcohol and aldehyde dehydrogenase
      enzymatic activities. This study describes the ADP-ribosylation of EhADH2. This
      modification did not have an effect on the enzymatic activities, but it may
      regulate other functions of EhADH2.

PMID- 16086107
TI  - Degradation of chlorophenols using pentachlorophenol-degrading bacteria
      Sphingomonas chlorophenolica in a batch reactor.
AB  - Chlorophenols are common environmental contaminants that have been used as the
      major component in wide-spectrum biocides in industry and agriculture. Many
      chlorophenols tend to persist in the environment and may become public health
      hazards. This research studied the ability of the pentachlorophenol (PCP)
      degrading bacterium Sphingomonas chlorophenolica to degrade and dechlorinate
      other chlorophenols. In addition, the characteristics of S. chlorophenolica were
      also investigated. When S. chlorophenolica cells were preincubated with PCP, the
      lag phase PCP degradation periods became shorter and the PCP concentrations that
      could be removed became higher. S. chlorophenolica was able to completely degrade
      2,3,6-trichlorophenol (2,3,6-TCP), 2,4,6-trichlorophenol (2,4,6-TCP), 2,3,4,6
      tetrachlorophenol (2,3,4,6-TeCP), and PCP within 38.1, 15.1, 11.8, and 11.8 h,
      and to release concentrations of 50.1, 60.9, 63.7, and 58.5 mg/L chloride at the
      same period of time. In the presence of supplementary carbon sources, the PCP
      removal efficiency increased with the presence of glucose or pyruvate. However,
      the removal efficiency of 75 mg/L 2,4-dichlorophenol did not increase with
      supplemental carbon sources.

PMID- 16086108
TI  - A histomorphometric study of cortical bone of the iliac crest in patients treated
      with glucocorticoids.
AB  - The effects of glucocorticoids on cancellous bone remodeling and structure are
      well documented but there are no reported histomorphometric studies in human
      cortical bone in glucocorticoid-treated patients. We have performed a
      histomorphometric analysis of iliac crest cortical bone in 14 patients treated
      with glucocorticoids, 9 females and 5 males, aged 18 to 48 years (34.1 +/- 7
      years) (mean +/- standard deviation [SD]). The underlying disease was cystic
      fibrosis in 8 patients; asthma 3; and nephrotic syndrome; Crohn disease and
      inflammatory pseudotumor of the liver in one patient each. Results were compared
      with an age-matched control group of 10 premenopausal women and 4 men aged 22 to
      38 years (30.1 +/- 4.8 years) who were not, however matched for underlying
      disease. Cortical bone indices were assessed by image analysis. Cortical width
      and area were similar in the two groups. However, cortical porosity, Haversian
      canal number, and density were higher in patients treated with glucocorticoids
      compared with controls (8.4 +/- 8.9% vs. 5.1 +/- 3.9%; P = 0.03) (45.9 +/- 23.2
      vs. 31.9 +/- 24.4; P =0.003) (13.7 +/- 9.4 vs. 6.7 +/- 3.3/mm2; P = 0.00005).
      Haversian canal area did not differ significantly between groups. The mean wall
      width of the osteons, bone formation rate (microm2/microm/day) and mineral
      apposition rate (microm/day) were lower in treated patients compared to controls
      (48.8 +/- 7.1 microm vs. 59.8 +/- 12.9 microm; P = 0.01) (0.056 +/- 0.040 vs.
      0.095 +/- 0.058; P = 0.05) and (0.59 +/- 0.12 vs. 0.75 +/- 0.11; P = 0.002). The
      proportion of canals with an eroded surface was lower in the treated compared
      with the control group, although this difference was not statistically
      significant. These results demonstrate that cortical porosity is increased in
      patients treated with long-term glucocorticoid therapy, due mainly to an increase
      in the number rather than size of Haversian canals. This may be because of
      increased bone resorption during the early stages of glucocorticoid therapy, in
      combination with long-term impairment of bone formation. Effects of the
      underlying disease on bone remodeling may also contributed to these changes and
      could not be excluded in the present study; since control subjects were not
      matched in terms of disease status.

PMID- 16086109
TI  - Mapping and modeling the biogeochemical cycling of turf grasses in the United
      States.
AB  - Turf grasses are ubiquitous in the urban landscape of the United States and are
      often associated with various types of environmental impacts, especially on water
      resources, yet there have been limited efforts to quantify their total surface
      and ecosystem functioning, such as their total impact on the continental water
      budget and potential net ecosystem exchange (NEE). In this study, relating turf
      grass area to an estimate of fractional impervious surface area, it was
      calculated that potentially 163,800 km2 (+/- 35,850 km2) of land are cultivated
      with turf grasses in the continental United States, an area three times larger
      than that of any irrigated crop. Using the Biome-BGC ecosystem process model, the
      growth of warm-season and cool-season turf grasses was modeled at a number of
      sites across the 48 conterminous states under different management scenarios,
      simulating potential carbon and water fluxes as if the entire turf surface was to
      be managed like a well-maintained lawn. The results indicate that well-watered
      and fertilized turf grasses act as a carbon sink. The potential NEE that could
      derive from the total surface potentially under turf (up to 17 Tg C/yr with the
      simulated scenarios) would require up to 695 to 900 liters of water per person
      per day, depending on the modeled water irrigation practices, suggesting that
      outdoor water conservation practices such as xeriscaping and irrigation with
      recycled waste-water may need to be extended as many municipalities continue to
      face increasing pressures on freshwater.

PMID- 16086110
TI  - Cervical leptomeningeal and intramedullary metastasis of a cerebral PNET in an
      adult.

PMID- 16086111
TI  - Multi-focal gliosarcoma: a case report and review of the literature.
AB  - Gliosarcoma (GS) is an uncommon malignant brain tumor with biphasic tissue
      pattern consisted of both glial and sarcomatous components. It usually occurs in
      adult population of middle age. We report a rare case of multi-focal GS that was
      initially interpreted as metastases of extra-cranial tumor. The histological
      examination revealed the biphasic pattern of a GS. The patient was treated with
      postoperative external radiation therapy and had poor prognosis. To our knowledge
      this is the second published case of GS with multi-focal presentation. In this
      study we also review the literature on clinicopathological aspects of GS.

PMID- 16086112
TI  - Combined razoxane and radiotherapy for melanoma brain metastases. a retrospective
      analysis.
AB  - We retrospectively compared the efficacy of razoxane and radiotherapy with
      radiotherapy alone or in combination with a non-razoxane based medication in
      patients with melanoma brain metastases. From 19 assessable patients receiving
      whole brain irradiation with or without a boost (mean total dose 40.5 Gy) for
      measurable brain metastases, 8 patients underwent an additional razoxane therapy
      with 125 mg per os twice daily started 5 days before radiotherapy and given
      throughout the whole radiation period. The median razoxane dose was 6.25 g (range
      3.2-8.0 g). Endpoints included radiation response rates, median survival time and
      1-year survival rates. To generate reliable prognostic parameters for this non
      randomized study population, the Score Index for Stereotactic Radiosurgery and
      the Radiation Therapy Oncology Group Recursive Partitioning Analysis score were
      applied. Radiotherapy with razoxane led to higher response rates (62% vs. 27%)
      and a lower percentage of progressive disease (12.5% vs. 36%) if compared with
      radiotherapy alone or with a non-razoxane based medication. This combination was
      associated with a longer median survival (5 months vs. 2.2 months; P=0.052) and a
      1-year survival rate of 37.5% vs. 0% (P=0.027). Both treatment groups belonged to
      similar prognosis subsets. The treatment was well tolerated. Taken together our
      data support the therapeutic concept of a combined razoxane radiation therapy in
      melanoma patients with brain metastases. The favorable treatment effects are
      probably due to the radiosensitizing and the cytorallentaric mode of action of
      razoxane. Since the patient numbers are low, confirmatory studies are certainly
      necessary.

PMID- 16086113
TI  - An international forum for discussion of gastric cancer is needed, particularly
      now.

PMID- 16086114
TI  - Laparoscopic surgery for GIST: too soon to decide.

PMID- 16086115
TI  - Risk factors for pancreas-related abscess after total gastrectomy.
AB  - BACKGROUND: European clinical trials of gastrectomy have shown that pancreas
      related complications are the major cause of mortality. The aim of this study was
      to determine the risk factors for pancreas-related abscess after gastrectomy and
      to evaluate the effects of the abscess on postoperative mortality. METHODS:
      Between 1992 and 1999, 663 consecutive patients with gastric carcinoma underwent
      total gastrectomy. Data from these patients were analyzed, to identify the
      predictors of pancreas-related abscess caused by pancreatic juice leakage, by a
      multiple logistic regression model. RESULTS: On multivariate analysis, increasing
      age (P = 0.018) and body mass index (P = 0.006) were independent preoperative
      risk factors. Dissection along the distal splenic artery was an intraoperative
      risk factor. The hazard ratios were increased 9.13-fold (P = 0.000) with a
      pancreas-preserving operation and 16.72-fold (P = 0.000) by distal
      pancreatectomy. Patients with the abscess had a higher postoperative mortality
      rate (P = 0.008), and a higher re-operation rate (P < 0.001) than patients
      without the abscess. CONCLUSION: Pancreas-related abscess is more likely to occur
      in older, obese patients undergoing node dissection along the distal splenic
      artery. Abscess formation is associated with a higher mortality and re-operation
      rate. Spleen preservation should be evaluated in Japan.

PMID- 16086116
TI  - Prognostic significance of intraperitoneal cancer cells in gastric carcinoma:
      detection of cytokeratin 20 mRNA in peritoneal washes, in addition to detection
      of carcinoembryonic antigen.
AB  - BACKGROUND: In patients with gastric cancer, the presence of gastric cancer cells
      in the peritoneal cavity detected by cytologic examination, is a significant
      prognostic factor. A more sensitive, reverse transcriptase-polymerase chain
      reaction (RT-PCR) technique, amplifying carcinoembryonic antigen (CEA), was
      introduced as a new detection system, but produced some false-positive results. A
      search for other molecular markers is ongoing. METHODS: Peritoneal washes were
      obtained from 195 patients with gastric carcinoma during surgery. Cytokeratin 20
      (CK20) mRNA levels were quantified, in addition to those of CEA, using the
      LightCycler, and the feasibility of CK20 as a target was evaluated. RESULTS: CK20
      was limited, in terms of sensitivity, for detecting disseminated cancer cells
      (sensitivity, 63%; specificity, 91%; positive predictive value, 70%; and negative
      predictive value, 88%). Multimarker analysis was performed, in which samples
      positive for either CK20 or CEA mRNA were considered to be positive for cancer
      cells. Multivariate analysis identified the multimarker analysis as a significant
      independent prognostic determinant. CONCLUSION: CK20 RT-PCR produced information
      that could add a significant impact to the knowledge obtained by CEA RT-PCR,
      although detection by CK20 alone was not sufficiently sensitive to replace CEA in
      the detection system.

PMID- 16086117
TI  - Indications for gastrectomy after incomplete EMR for early gastric cancer.
AB  - BACKGROUND: Although the number of patients with early gastric cancer (EGC)
      treated by endoscopic mucosal resection (EMR) has increased, the appropriate
      strategy for treating those with incomplete resection has not been established.
      METHODS: This study analyzed 726 cases of EGC in patients treated by EMR between
      1991 and 2000, in order to clarify the en-bloc and complete resection rates. We
      classified patients with incomplete resection into four groups according to the
      estimated risk of residual cancer or lymph node (LN) metastasis, determined from
      pathological findings of EMR specimens. We then analyzed 45 patients with EGC
      treated surgically after incomplete EMR, with the aim of eliciting the risk of
      residual cancer and LN metastasis. RESULTS: Of the 726 patients, 529 (72.9%) had
      an en-bloc resection, while 378 (52.1%) had a complete resection. Three hundred
      and nine patients were found to have mucosal cancer and lateral cut-end-positive
      status with no LN metastasis (group A). In this group, 18 patients (5.8%) had
      residual cancer, with the lesions in the majority of patients being limited to
      the mucosal layer. Group B consisted of 14 patients with differentiated and
      submucosal (sm1) depth cancers, with 1 patient having residual cancer and 2
      patients having LN metastasis. Fifteen patients were classified as group C, with
      sm2 or greater and vertical cut end-negative status, with 2 showing residual
      cancer and 1 showing LN metastasis. Group D included 10 patients with vertical
      cut end-positive status. Four of these patients had residual cancer while 1 had
      LN metastasis. CONCLUSION: We recommend that patients in group A should have
      close follow-up or endoscopic treatment, while those in groups B, C, or D should
      be treated by gastrectomy associated with LN dissection.

PMID- 16086118
TI  - VEGF significance in peritoneal recurrence from gastric cancer.
AB  - BACKGROUND: In gastric cancer, the management of peritoneal dissemination in the
      Peritoneal cavity is extremely important; however, peritoneal dissemination in
      the final stage of gastric cancer remains untreatable. Peritoneal dissemination
      involves several steps, including tumor-cell attachment, invasion, and growth in
      the peritoneum. Many cytokines, growth factors, matrix metalloproteinases (MMPs),
      and angiogenic factors play important roles in these steps. So far, few studies
      have investigated the correlation, if any, between peritoneal dissemination and
      the angiogenic factor, vascular endothelial growth factor (VEGF). METHODS:
      Immunohistochemical staining, using the avidin-biotin peroxidase complex method,
      was performed on slides of surgical specimens from 40 patients with stage II
      gastric cancer with serosal invasion, who underwent surgery at our hospital
      between 1990 and 2000. Anti-human VEGF rabbit polyclonal IgG was used as the
      primary antibody. VEGF expression was classified in one of four categories
      depending on the percentage of tumor-cell staining (P). VEGF expression was also
      classified in one of three categories depending on the staining intensity (I).
      The VEGF expression score was calculated as P x I. RESULTS: There were ten
      patients with peritoneal recurrence. Of these, seven had macroscopic type-4
      scirrhous-type gastric carcinoma. In the immunohistochemical study, the VEGF
      score of patients with peritoneal recurrence was 9.40 +/- 2.46; on the other
      hand, that of patients without peritoneal recurrence was 3.47 +/- 2.36. The VEGF
      score of patients with peritoneal recurrence was significantly higher than that
      of patients without peritoneal recurrence. In patients with macroscopic type 4,
      the VEGF score of those with peritoneal recurrence was 9.14 +/- 2.19, while on
      the other hand, that of the patients without peritoneal recurrence was 3.80 +/-
      3.03. The VEGF score of these patients with peritoneal recurrence was
      significantly higher than that of those without peritoneal recurrence. The
      survival rate in the VEGF low-expression group was significantly higher than that
      in the VEGF high-expression group. Multivariate analysis showed that the VEGF
      score was a significant parameter of peritoneal recurrence. CONCLUSION: These
      results suggested that VEGF was correlated with peritoneal metastasis from
      gastric cancer, and that VEGF was a useful indicator of peritoneal recurrence.

PMID- 16086119
TI  - Microsatellite instability is linked to loss of hMLH1 expression in advanced
      gastric cancers: lack of a relationship with the histological type and phenotype.
AB  - BACKGROUND: It has been suggested that the prevalence of microsatellite
      instability (MSI) is high in intramucosal differentiated gastric cancers with
      gastric foveolar phenotypic expression, and that these tumors are prone to lose
      their glandular structures and progress to undifferentiated-type lesions. To test
      this hypothesis, we examined the relationships among human MutL homologue 1
      (hMLH1) expression (which is linked to MSI), the phenotype, and the histological
      type in patients with advanced and intramucosal gastric cancer. METHODS: We
      analyzed hMLH1 expression by immunohistochemistry in 70 advanced and 30
      intramucosal gastric cancers with histological evaluation and assessment of the
      phenotype, and Cdx2 expression determined by immunohistochemistry. The MSI status
      was also examined in 20 cases. RESULTS: Thirteen (18.6%) advanced and 5 (16.7%)
      intramucosal gastric cancers were judged to be hMLH1-negative. In the advanced
      cases, no association was observed between the histological type and the
      phenotype and loss of hMLH1. In the intramucosal cases, MUC5AC expression was
      observed in all 5 hMLH1-negative differentiated-type cancers. However, no hMLH1
      negative lesions were detected in the intramucosal undifferentiated cancers
      (0/14; P < 0.05 vs differentiated types). In the advanced cases, MSI-positivity
      (MSI +) and loss of hMLH1 expression did correlate (P < 0.0001), while no
      association was observed between MSI +, histological type, and phenotype.
      CONCLUSION: Our data support the hypothesis that, phenotypically, some MSI
      positive differentiated gastric cancers of gastric foveolar phenotypic expression
      may easily change, from gastric to intestinal phenotypic expression, also
      changing, histologically, from differentiated to undifferentiated type with
      progression.

PMID- 16086120
TI  - Gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor.
AB  - We report a case of adenosquamous carcinoma of the stomach that produced
      granulocyte-colony stimulating factor (G-CSF). The patient, who had an admission
      diagnosis of advanced gastric cancer, had marked leukocytosis without evidence of
      infection. After leukemia and metastatic leukemoid reaction were excluded by bone
      marrow examination, a G-CSF-producing cancer was suspected as the cause of the
      abnormally elevated serum G-CSF level. The resected stomach tumor was
      histologically diagnosed as adenosquamous carcinoma; positive expression of G-CSF
      by tumor cells was shown with immunohistochemical detection, which confirmed the
      preoperative diagnosis. Recurrent disease in the liver and lymph nodes,
      accompanied by leukocytosis and re-elevation of serum G-CSF, developed just 3
      months after the curative gastrectomy and adjuvant chemotherapy. All of the
      recurrent disease was resected, restoring normal levels of serum G-CSF. The
      patient survived for almost 2 years after the initial surgery with extensive
      chemotherapy, including weekly treatment with paclitaxel, before finally
      succumbing to liver failure secondary to extensive liver metastasis.

PMID- 16086121
TI  - Primary gastric choriocarcinoma: two case reports and a pooled analysis of 53
      cases.
AB  - Primary gastric choriocarcinoma (PGC) is a rare tumor. In total, approximately
      140 cases of PGC have been reported in the international medical literature.
      However, the clinical behavior, tumor characteristics, and prognostic parameters
      of PGC have not been clearly described. We conducted a pooled analysis to clarify
      the tumor characteristics and prognostic parameters in 53 patients with PGCs,
      including 2 patients treated at our hospital. The following variables were
      examined as potential prognostic factors: (1) sex, (2) age, (3) depth of
      invasion, (4) size, (5) histology, (6) nodal metastasis, (7) distant lymph node
      metastasis, (8) synchronous liver metastasis, (9) residual tumor, and (10)
      chemotherapy (not given or given). Univariate and multivariate analyses showed
      that the presence of residual tumor and synchronous liver metastasis and the
      absence of chemotherapy were significantly associated with an increased hazard
      rate (HR) of short overall survival (OS). Pooled analysis, including the two
      patients with PGC treated at our facility, demonstrated that the presence of a
      curative operation and chemotherapy, and the absence of synchronous liver
      metastasis were the strongest indicators of a favorable clinical course in
      patients with PGC.

PMID- 16086122
TI  - Hand-assisted laparoscopic surgery for a large gastrointestinal stromal tumor of
      the stomach.
AB  - We report two cases of large gastrointestinal stromal tumor (GIST) of the stomach
      that were successfully treated by hand-assisted laparoscopic surgery (HALS). Two
      patients, a 56-year-old woman and a 60-year-old man, were admitted to our
      department for the treatment of a large submucosal tumor of the stomach. After
      gastrointestinal endoscopy, ultrasonography, computed tomography, and magnetic
      resonance imaging, we suspected that the masses, measuring 7.0 cm and 8.0 cm in
      diameter, respectively, were GISTs in the stomach. However, preoperatively, we
      could not rule out the possibility of malignant neoplasms, because they had been
      bleeding or gradually growing. Hand-assisted laparoscopic wedge resection was
      safely performed for the diagnosis and treatment of the submucosal tumor of the
      stomach. The immunohistochemical diagnosis in both patients was GIST of the
      stomach with intermediate-grade malignancy. HALS may be a good indication for
      large GISTs of the stomach that are difficult to diagnose preoperatively, whether
      they are malignant or benign, because it is safe and minimally invasive,
      promoting rapid recovery.

PMID- 16086123
TI  - Metastatic breast cancer presenting as linitis plastica of the stomach.
AB  - Early detection and treatment of breast cancer, leading to longer survival, has
      revealed the natural history of this disease process. Linitis plastica of the
      stomach is a potential long-term sequela of metastatic breast cancer. Here we
      present a case of metastatic breast cancer presenting as linitis plastica, as
      well as the treatment algorithm for this rare clinical entity. The world
      literature describes a clear pattern of linitis plastica for metastatic
      infiltrating lobular breast cancer and a discrete nodular pattern for
      infiltrating ductal cancer, in regard to metastasis to the stomach. To our
      knowledge, this is the first case of infiltrating ductal cancer presenting as
      linitis plastica of the stomach.

PMID- 16086124
TI  - Aggressive G-CSF-producing gastric cancer complicated by lung and brain
      abscesses, mimicking metastases.
AB  - A 57-year-old Japanese man had type II c gastric cancer with marked lymph node
      metastases associated with leukocytosis and elevated granulocyte colony
      stimulating factor (G-CSF). Total gastrectomy and distal pancreatectomy with
      lymph node dissection were performed. Although the primary lesion was negative
      for G-CSF by histopathological immunostaining, a highly increased G-CSF m-RNA
      level, measured using reverse transcriptase-polymerase chain reaction in frozen
      sections, led to a diagnosis of G-CSF-producing gastric cancer. The leukocytes
      and G-CSF decreased immediately after surgery. He then had an intraabdominal
      recurrence, and was diagnosed with multiple tumors in his lung and brain, with
      abnormally elevated leukocytes and greatly increased G-CSF; he died 4 months
      after the surgery. Autopsy showed intraabdominal recurrence of cancer, with no
      metastases to the lung or brain, but with multiple brain and lung abscesses. We
      speculate that the excessively increased neutrophils induced by G-CSF infiltrated
      the lung and brain and formed abscesses, mimicking metastases.

PMID- 16086125
TI  - Gastric cancer invading the pancreas.

PMID- 16086126
TI  - Evidence-based medicine and medicine-based evidence.

PMID- 16086127
TI  - Modern psychophysical tests to assess olfactory function.
AB  - The sense of smell significantly contributes to quality of life. In recent years
      much progress has been made in understanding the biochemistry, physiology and
      pathology of the human olfactory system. Olfactory disorders may arise not only
      from upper airway phlogosis but also from neurodegenerative disease. Hyposmia may
      precede motor signs in Parkinson's disease and cognitive deficit in Alzheimer's
      disease. These findings suggest the complementary role of olfactory tests in the
      diagnosis and management of neurodegenerative diseases. In this report we present
      a review of modern olfactory tests and their clinical applications. Although
      rarely employed in routine clinical practice, the olfactory test evaluates the
      ability of odour identification and is a useful diagnostic tool for olfaction
      evaluation. Olfactory screening tests are also available. In this work we
      strongly recommend the importance of an ENT evaluation before the test
      administration and dissuade from a self-administration of an olfactory test.

PMID- 16086128
TI  - Olfactory screening test in mild cognitive impairment.
AB  - Mild cognitive impairment (MCI) is a transient status between physiologic ageing
      and dementia. Each year more than 12% of subjects with MCI develop Alzheimer's
      disease. This study evaluated the presence of an olfactory deficit in amnesic MCI
      (aMCI) patients. Twenty-nine patients diagnosed with aMCI and a homogeneous
      control group of 29 subjects were enrolled in the study. Olfactory function was
      assessed by the Sniffin' Sticks Screening Test (SSST) and the Mini Mental State
      Examination, the Clinical Dementia Rating, the Geriatric Depression Scale and the
      Mental Deterioration Battery were used to evaluate the neurocognitive status.
      aMCI patients showed a significant impairment of their olfactory identification
      compared to controls (SSST score: 8.3+/-2.1 vs. 10.8+/-0.9; p<0.001). These
      results suggest that olfactory tests should be part of the diagnostic
      armamentarium of pre-clinical dementia. A long-term follow up might confirm the
      olfactory identification function as an early and reliable marker in the
      diagnosis of pre-clinical dementia.

PMID- 16086129
TI  - Temporal gradients for media-mediated memory: Italian norms.
AB  - Temporal gradient (TG), i.e., differential recall of recent and old memories, is
      a well known feature of amnesia. A recent study provided evidence of a classical
      TG for media-mediated events in elderly healthy people, showing that they recall
      remote events significantly better than recent ones, while a reverse TG, i.e.,
      better recall of more recent events, was demonstrated in younger normal subjects.
      In the present study we present normative data which, using the same test, allow
      evaluation of TG in single cases and their qualification as classical or reverse.
      The normative procedure was also applied to a small sample of subjects with
      probable Alzheimer's disease or mild cognitive impairment. Norms for TG may be
      helpful not only to assess healthy people's performance, but also to judge any
      apparent TG in pathological subjects.

PMID- 16086130
TI  - Olanzapine therapy in hallucinatory visions related to Bonnet syndrome.
AB  - Charles Bonnet syndrome (CBS) is characterised by the triad of complex visual
      hallucinations, ocular pathology causing visual deterioration and preserved
      cognitive status. We report a case of a 62-year-old man with a brief history of
      visual hallucinations. The patient complained of amaurosis with optic nerve
      atrophy in his left eye and a severe impairment of visual acuity in the right and
      suddenly experienced complex, vivid, elaborate and coloured visual hallucinations
      persisting long after eye closure and stopping during sleep. The patient
      maintained his insight, criticising these visions as unreal and felt distressed
      by them. Hallucination onset was 3 days before hospital admission. No cognitive
      impairment and no diseases apart from prostatic adenoma treated with alpha-lythic
      therapy were reported. Neurological examination and neuroimaging data were
      normal. Therapy with olanzapine (OLZ) 5 mg/day led to a progressive clearance of
      visual hallucinations in seven days and was gradually reduced and withdrawn.
      Three months later the visions reappeared and OLZ 5 mg/day yielded a persisting
      remission so that at the follow-up examination after 1 year on therapy the
      patient is still asymptomatic. To date, no established treatment for CBS is
      stated and in some patients the hallucinations fade spontaneously; in our case an
      antipsychotic therapy with OLZ was effective while generally anticonvulsant drugs
      with different mechanism of action such as carbamazepine, valproate and
      gabapentin are proposed.

PMID- 16086131
TI  - Lung involvement in Niemann-Pick disease type C1: improvement with
      bronchoalveolar lavage.
AB  - Progressive lung infiltration is a major cause of death in Niemann-Pick disease
      type A and B (NPA, NPB) and in the recently defined type C2. In type C1 (NPC1),
      the main manifestations are neurological. We report a patient with a classic,
      neurological, late infantile form of NPC1 disease, carrying the mutation P474L
      and the variant I642M in the NPC1 gene, who suffered recurrent respiratory
      manifestations. Bronchoalveolar lavage of a lung segment due to deteriorating
      respiratory condition revealed many foamy macrophages and was followed by an
      improvement in symptoms. Pneumopathy may therefore be considered a feature of
      NPC1 disease for which a partial bronchoalveolar lavage could be a useful
      treatment.

PMID- 16086132
TI  - An unusual case of insomnia associated with Whipple encephalopathy: first case
      reported from Greece.
AB  - Whipple disease is a relapsing systemic illness caused by Tropheryma whippelii.
      Central nervous system involvement occurs in 5%-40% of all patients. Hypothalamic
      manifestations occur in 31% of Whipple encephalopathy, including polydipsia,
      hyperphagia, change in libido and insomnia. We report a case of a 48-year-old man
      with severe insomnia, depression, dementia, dysarthria, myoclonic movements of
      the limbs and ophthalmoplegia. The diagnosis of Whipple encephalopathy was
      confirmed by PCR analysis of blood and faeces. He received a full dose of
      antibiotic treatment. Despite clinical improvement, resolution of the lesions
      detected in MRI scan of the brain and negative results of the PCR in blood,
      faeces and cerebrospinal fluid six months later, insomnia persisted and finally
      subsided after the administration of carbamazepine (600 mg/day). Our case
      supports the finding that carbamazepine might be useful in the treatment of
      insomnia associated with Whipple encephalopathy.

PMID- 16086133
TI  - Fibrous dysplasia in combination with aneurysmal bone cyst presenting as a
      subarachnoid haemorrhage.
AB  - Fibrous dysplasia (FD) is a rare tumour, representing 2.5% of all bone tumours
      and 7% of benign tumours. Aneurysmal bone cyst (ABC) is also an uncommon
      pathology, usually associated with a secondary vascular lesion consisting of an
      arteriovenous malformation. In this article, we relate a case report of a young
      female with a rare combination of FD with aneurysmal bone cyst presenting as a
      subarachnoid haemorrhage (SAH). Despite the possibility of clinical treatment of
      these lesions, this report demonstrates that symptomatic lesions may be
      successfully managed by surgical resection. The authors' opinion is that this
      treatment should be individualised depending on particularities of each case,
      such as localisation of the lesion, biopsy results and image exams features. We
      also present a critical literature review of diagnostic methods and therapeutical
      options for both ABC and FD, with emphasis on controversial topics surrounding
      these issues.

PMID- 16086134
TI  - The structured assessment of depression in brain-damaged individuals: translation
      and validation study of the Italian version.
AB  - The aim of this study was to translate the structured assessment of depression in
      brain-damaged individuals (SADBD) questionnaire into the Italian language,
      validate, and test reliability and validity of the Italian version. Consecutive
      patients with stroke were screened in the Department of Neurology, Avogadro
      University in Novara and the Department of Neurorehabilitation, Maugeri
      Foundation, Veruno, Italy. Thirty patients were included in the study. The
      internal consistency ranged between 0.78 and 0.87. The intra-rater test-retest
      reliability was 0.93 for BDIderived items and 0.82 for HRSD-derived items; while
      the inter-rater test-retest reliability was 0.94 for BDI-derived items and 0.93
      for HRSD-derived items. Correlation between the SADBD diagnosis made by the
      physician and the nurse was 0.51; correlation between caregiver and physician
      diagnosis was 0.60. The Italian version of the SADBD was demonstrated to be
      acceptable, reliable and a valid measure of depression in patients with stroke.

PMID- 16086135
TI  - Telling about the stolen mind.
AB  - Art forms (music, painting, sculpture, literature and theatre) are essential
      components in all social and human contexts. The role of art, in this case of
      theatre, is to express a visual event that aims to help the spectator identify
      himself/herself in the characters. The play presented here is "A...come non so"
      and shows the characteristic aspects of Alzheimer's disease from the first stage
      of the disease to the last stage: amnesia, aphasia, agnosia and apraxia. It tells
      the story of Carlo Pontercoli, a gerontologist and specialist in cardiovascular
      disease, who, while writing his paper on "The elderly and sexuality", manifests
      the first signs of the disease that killed his mother not so long before. The
      monologue aims to be a new contribution to the whole understanding of the
      problems concerning Alzheimer's disease through observation and visual
      communication of those problems.

PMID- 16086136
TI  - Ehlers-Danlos syndrome in the parturient: an uncommon disorder--common dilemma in
      the delivery room.
AB  - DESCRIPTION: Ehlers-Danlos syndrome (EDS) is a rare genetically transmitted
      connective tissue disorder, non-specific to pregnancy. CONCLUSION: Because of
      multi-organ involvement and the varied presentations of this disease, no uniform
      obstetric and anesthetic recommendations regarding the peripartum care of these
      parturients can be made.

PMID- 16086137
TI  - [Disaster medical response concerns us all].
AB  - The flood disaster in the region of the Oder and Elbe Rivers or the disaster in
      Eschede, Kaprun, or Ramstein make us aware that disasters not only occur in
      distant regions of the world but also in our latitudes. They do not follow any
      rules; no one can predict the location, time, or type of a disaster. However,
      this lack of concrete predictability should not lead to our being unprepared to
      respond to catastrophic events. Detailed examination and analysis of medical and
      organizational activities involved in past disasters reveal that these types of
      incidents always entail similar medical and logistic consequences. Dealing with
      disasters necessitates cooperation between numerous organizations and people.
      This requires clearly structured facilities for information, communication, and
      decision making as well as a well-defined process flow. In addition to basic
      planning and practicing of these processes for medical management of catastrophes
      such as searching for and rescuing victims, triage, performing life-saving
      emergency procedures, definitive medical treatment, and transfer of patients
      establishing structures for disaster preparedness is indispensable to meet the
      demands of mass cases of ill or wounded individuals.

PMID- 16086138
TI  - [Chronic pain in everyday medical routine].
AB  - Acute or chronic pain are the most frequent reasons to seek medical help.
      Primarily acute pain is a symptom and warning sign. However, insufficient
      treatment of acute pain may induce a change to a chronic long lasting pain
      illness. Therefore a consequent immediate treatment is essential. Chronic pain is
      a bio-psycho-social illness. In this situation pharmacotherapy or any other
      monotherapy alone is no longer effective. Interdisciplinary treatment is needed.
      Effective treatment of acute pain to prevent from long lasting pain episodes is
      an essential and the only way to prevent from enormous financial consequences of
      chronic pain.

PMID- 16086139
TI  - [Mechanisms in the development of pain. Key issue in the periphery].
AB  - The interaction between neurons, tissue cells and inflammatory cells is of major
      importance for the development of pain in the periphery. In this interaction a
      variety of inhibitory and activating circuits has been identified in recent
      years. In addition to the receptors for classical inflammatory mediators on the
      sensory terminals like bradykinin, axonal ion channels have been identified as
      major modulators of pain and sensitization apart from their traditional role in
      conduction of action potentials. Sensitization of spinal nociceptive processing
      is crucial for the expansion of pain beyond the initially injured site and
      contributes to chronic pain. Learning processes and extinction of aversive memory
      are of major importance for the development, but also the therapy of chronic pain
      states.

PMID- 16086140
TI  - Visceral fat and beta cell function in non-diabetic humans.
AB  - AIMS/HYPOTHESIS: Preferential visceral adipose tissue (VAT) accumulation has been
      clearly associated with insulin resistance. In contrast, the impact of visceral
      obesity on beta cell function is controversial. METHODS: In 62 non-diabetic women
      and men (age 24-69 years, BMI 21-39 kg/m2), we measured VAT and subcutaneous
      adipose tissue (SAT) fat mass by magnetic resonance imaging. We also measured
      insulin secretion and beta cell function by C-peptide deconvolution and
      physiological modelling of data from a frequently sampled, 75-g, 3-h OGTT,
      respectively. RESULTS: VAT (range 0.1-3.1 kg) was strongly related to sex, age
      and BMI; SAT was related to sex and BMI. Controlling for sex, age, BMI and SAT by
      multivariate analysis, excess VAT was associated with a clinical phenotype
      comprising higher plasma glucose levels, BP, heart rate and serum transaminases.
      The corresponding metabolic phenotype consisted of insulin resistance (partial r=
      0.38) and hyperinsulinaemia (partial r=0.29). The latter, however, was
      appropriate for the degree of insulin resistance regardless of obesity and
      abdominal fat distribution. Moreover, none of the model-derived parameters
      describing beta cell function (glucose sensitivity, rate sensitivity and
      potentiation) was independently associated with excess VAT.
      CONCLUSIONS/INTERPRETATION: In non-diabetic Caucasian adults of either sex,
      preferential visceral fat deposition in itself is part of an insulin-resistant
      phenotype. The insulin secretory response to a physiological challenge is
      increased to fully compensate for the insulin resistance, but the dynamics of
      beta cell function (glucose sensitivity, rate sensitivity and potentiation) are
      largely preserved.

PMID- 16086141
TI  - Short-term visual deprivation alters neural processing of tactile form.
AB  - Blindness is known to alter the responsiveness of visual cortex. Recently,
      reversible visual deprivation by blindfolding has been shown to affect non-visual
      abilities as well as visual cortical function. Here we investigated the effect of
      2 h of blindfolding on cerebral cortical activation patterns during tactile form
      perception, using functional magnetic resonance imaging. Two form tasks were
      used, one requiring discrimination of global stimulus form and the other,
      detection of a gap in a bar. Blindfolded subjects showed significant deactivation
      during these tasks in regions that are intermediate in the hierarchy of visual
      shape processing: probable V3A and ventral intraparietal sulcus (vIPS). These
      regions lacked signal changes in controls. There were also task-specific
      increases in activation in blindfolded relative to control subjects, favoring the
      form over the gap task, along the IPS and in regions of frontal and temporal
      cortex. We also found alterations of functional connectivity that corresponded to
      the activity differences, with the emergence of correlated activity between the
      vIPS and V3A in blindfolded subjects. We conclude that blindfolding sighted
      individuals for a 2-h period induces significant changes in the neural processing
      of tactile form, probably reflecting short-term neural plasticity.

PMID- 16086142
TI  - Integration of visual and tactile stimuli: top-down influences require time.
AB  - In a visuotactile congruency task, a distracting flash of light presented near a
      tactile target can influence speeded judgments of tactile location. Localization
      of the tactile target is more rapid when the elevation of the visual distractor
      is congruent with the tactile stimulus than when it is incongruent. The goal of
      the present study was to examine the degree of control that can be exerted on the
      process proposed to integrate the visual and tactile stimuli. To this end, the
      proportion of spatially congruent items was manipulated across blocks of trials.
      A robust congruency effect was observed across three experiments. There was no
      effect of proportion congruency (varied between 75 and 11% congruent) when the
      visual event was presented only 30 ms prior to the tactile event. When this lead
      time was increased to 100 ms there was a significant increase in the congruency
      effect, for errors, in the high proportion congruent conditions (experiment 3).
      We conclude that with sufficient lead-time, top-down influence can be exerted in
      this task, however, when presented at near simultaneity, visuotactile integration
      is independent of top-down effects.

PMID- 16086143
TI  - Biasing the brain's attentional set: II. effects of selective intersensory
      attentional deployments on subsequent sensory processing.
AB  - This study used high-density mapping of human event-related potentials to examine
      the brain activity associated with selective information processing when subjects
      were cued on a trial-by-trial basis to perform a discrimination in either the
      visual or auditory modality. On each trial, word-cues (S1) instructed subjects to
      attend to features within one sensory-modality of an impending compound auditory
      visual stimulus (S2) that arrived approximately 1-second following the cue.
      Subjects made a discrimination within the cued modality of the S2 stimulus. The
      spatio-temporal patterns of activity in response to the compound S2 stimulus were
      examined as a function of the sensory modality being attended. The earliest
      effects of intersensory attention on visual processing were seen subsequent to
      the initial activation of visual cortex, beginning at 80 ms and continuing into
      the P1 and N1 components of the visual ERP. The scalp-topography of this earliest
      modulation was consistent with modulation of activity in ventral visual stream
      areas. Thus, the locus of effects on visual S2 processing differed from the
      anticipatory parieto-occipital biasing activity that preceded S2 presentation.
      This pattern of effects strongly suggests that the anticipatory activity
      (following the cue) associated with sustaining the focus of attention during
      intersensory attention, at least in the context of this paradigm, does not
      operate as a simple gain mechanism in early visual sensory areas. Rather,
      attentional biasing can operate through a higher-order process whereby parieto
      occipital cortices influence the subsequent flow of visual processing in the
      ventral stream.

PMID- 16086144
TI  - Biasing the brain's attentional set: I. cue driven deployments of intersensory
      selective attention.
AB  - Brain activity associated with directing attention to one of two possible sensory
      modalities was examined using high-density mapping of human event-related
      potentials. The deployment of selective attention was based on visually presented
      symbolic cue-words instructing subjects on a trial-by-trial basis, which sensory
      modality to attend. We measured the spatio-temporal pattern of activation in the
      approximately 1 second period between the cue-instruction and a subsequent
      compound auditory-visual imperative stimulus. This allowed us to assess the flow
      of processing across brain regions involved in deploying and sustaining inter
      sensory selective attention, prior to the actual selective processing of the
      compound audio-visual target stimulus. Activity over frontal and parietal areas
      showed sensory specific increases in activation during the early part of the
      anticipatory period (~230 ms), probably representing the activation of fronto
      parietal attentional deployment systems for top-down control of attention. In the
      later period preceding the arrival of the "to-be-attended" stimulus, sustained
      differential activity was seen over fronto-central regions and parieto-occipital
      regions, suggesting the maintenance of sensory-specific biased attentional states
      that would allow for subsequent selective processing. Although there was clear
      sensory biasing in this late sustained period, it was also clear that both
      sensory systems were being prepared during the cue-target period. These late
      sensory-specific biasing effects were also accompanied by sustained activations
      over frontal cortices that also showed both common and sensory specific
      activation patterns, suggesting that maintenance of the biased state includes top
      down inputs from generators in frontal cortices, some of which are sensory
      specific regions. These data support extensive interactions between sensory,
      parietal and frontal regions during processing of cue information, deployment of
      attention, and maintenance of the focus of attention in anticipation of impending
      attentionally relevant input.

PMID- 16086145
TI  - Influence of expiratory flow-limitation during exercise on systemic oxygen
      delivery in humans.
AB  - To determine the effects of exercise with expiratory flow-limitation (EFL) on
      systemic O(2) delivery, seven normal subjects performed incremental exercise with
      and without EFL at approximately 0.8 l s(-1) (imposed by a Starling resistor in
      the expiratory line) to determine maximal power output under control (W'(max,c))
      and EFL (W'(max,e)) conditions. W'(max,e) was 62.5% of W'(max,c), and EFL
      exercise caused a significant fall in the ventilatory threshold. In a third test,
      after exercising at W'(max,e) without EFL for 4 min, EFL was imposed; exercise
      continued for 4 more minutes or until exhaustion. O(2) consumption (V'(O)(2)) was
      measured breath-by-breath for the last 90 s of control, and for the first 90 s of
      EFL exercise. Assuming that the arterio-mixed venous O(2) content remained
      constant immediately after EFL imposition, we used V'(O)(2) as a measure of
      cardiac output (Q'(c)). Q'(c) was also calculated by the pulse contour method
      with blood pressure measured continuously by a photo-plethysmographic device.
      Both sets of data showed a decrease of Q'(c) due to a decrease in stroke volume
      by 10% (p < 0.001 for V'(O)(2)) with EFL and remained decreased for the full 90
      s. Concurrently, arterial O(2) saturation decreased by 5%, abdominal, pleural and
      alveolar pressures increased, and duty cycle decreased by 43%. We conclude that
      this combination of events led to a decrease in venous return secondary to high
      expiratory pressures, and a decreased duty cycle which decreased O(2) delivery to
      working muscles by approximately 15%.

PMID- 16086146
TI  - Effect of joint angle on mechanomyographic amplitude during unfused and fused
      tetani in the human biceps brachii muscle.
AB  - The influence of muscle length-dependent changes in contractile properties on the
      mechanomyogram (MMG) was investigated during evoked contractions of the biceps
      brachii muscle. The biceps of nine healthy subjects was stimulated by single
      twitches, unfused (10 Hz), and fused (30 Hz) frequencies at elbow joint angles of
      75, 90, 105, 120, 135, and 150 degrees. During evoked contractions, the
      longitudinal movement was estimated by the fluctuation of torque signal, and the
      lateral movement was detected by MMG. Contraction time and half relaxation time
      were calculated from the single twitches. For repetitive stimulations, followed
      by eliminating DC component from torque signals, the root mean square values
      calculated from the torque and MMG signals, which were torque fluctuation and RMS
      MMG, respectively. For the 10 Hz stimulation condition, reductions in the torque
      fluctuation and RMS-MMG were concomitantly observed with increasing elbow angle,
      and there was a significant correlation between the torque fluctuation and RMS
      MMG. On the other hand, for 30 Hz stimulation, there were no significant
      differences in the torque fluctuation and RMS-MMG over all elbow angles, and no
      significant correlation between the two parameters. Moreover, the torque
      fluctuation and RMS-MMG for 10 Hz stimulation were correlated with the
      contraction time and half relaxation time obtained at each elbow angle, while
      there were no correlations for the 30 Hz condition. These data suggest that MMG
      could be a reliable tool to study the development of fusion and the changes in
      muscle contractile properties during repetitive unfused contractions.

PMID- 16086147
TI  - Testing knee extension and flexion strength at different ranges of motion: an
      isokinetic and electromyographic study.
AB  - The main objective of this study was to explore the mechanical and electrical
      output of thigh muscles derived from a range of motion (RoM) of 90 degrees (0-90
      degrees flexion, LR) and the three successive RoMs: 0-30 degrees (SR1), 30-60
      degrees (SR2) and 60-90 degrees (SR3). Thirteen men took part in the study. In
      view of the torque-velocity relationship and in order to render the test
      conditions as equivalent as possible, LR was tested at 90 degrees /s while the
      corresponding velocity for all SRs was 30 degrees /s. The findings indicated very
      good agreement between LR and SR2 in terms of absolute strength (particularly the
      concentric), within muscle eccentric to concentric strength ratios, between
      muscles (agonist to antagonist) strength ratios and the normalized IEMG
      (expressed in muV/Nm). An agreement was also noted between the mean eccentric
      peak torque of the knee flexors at LR and SR1 and between the mean eccentric peak
      torque of the knee extensors at LR and SR3. However, in general there was a
      lesser agreement between LR and SR1 or SR3. It is suggested that testing thigh
      muscles in the middle sector of knee motion (SR2) yields strength and EMG data
      that are close and well correlated with those derived from testing the knee along
      the commonly used (0-90 degrees ) RoM.

PMID- 16086148
TI  - Baroreflex sensitivity assessment and heart rate variability: relation to
      maneuver and technique.
AB  - In the present study, we examined two baroreflex sensitivity (BRS) issues that
      remain uncertain: the differences among diverse BRS assessment techniques and the
      association between BRS and vagal outflow. Accordingly, the electrocardiogram and
      non-invasive arterial pressure were recorded in 27 healthy subjects, during
      supine with and without controlled breathing, standing, exercise, and recovery
      conditions. Vagal outflow was estimated by heart rate variability indexes,
      whereas BRS was computed by alpha-coefficient, transfer function, complex
      demodulation in low- and high-frequency bands, and by sequence technique. Our
      results indicated that only supine maneuvers showed significantly greater BRS
      values over the high frequency than in the low-frequency band. For maneuvers at
      the same frequency region, supine conditions presented a larger number of
      significant differences among techniques. The plots between BRS and vagal
      measures depicted a funnel-shaped relationship with significant log-log
      correlations (r=0.880-0.958). Very short latencies between systolic pressure and
      RR interval series in high-frequency band and strong log-log correlations between
      frequency bands were found. Higher variability among different baroreflex
      measurements was associated with higher level of vagal outflow. Methodological
      assumptions for each technique seem affected by non-baroreflex variation sources,
      and a modified responsiveness of vagal motoneurons due to distinct stimulation
      levels for each maneuver was suggested. Thus, highest vagal outflows corresponded
      to greatest BRS values, with maximum respiratory effect for the high-frequency
      band values. In conclusion, BRS values and differences across the tested
      techniques were strongly related to the vagal outflow induced by the maneuvers.

PMID- 16086149
TI  - [Safety-relevant performance of patients on chronic opioid therapy].
AB  - AIM: Is there a difference in performance and psychomotor function between
      patients on chronic opioid therapy and healthy controls and which factors
      influence the performance of the patients? METHODS: A total of 80 patients and
      243 healthy controls were investigated with computer-based tests concerning
      concentration, coordination, reaction time, vigilance, and perception. RESULTS:
      The patients' results were worse in the test for concentration and better in the
      test for coordination than the results of the healthy controls. The results in
      the tests for reaction time, vigilance, and perception did not significantly
      differ between the two groups. Patients receiving an antidepressant in addition
      to the opioid were worse in the test for concentration than patients without
      antidepressant. Patients older than 50 years were impaired in four of five tests,
      and patients driving a car within the last 12 months had better results than
      patients without driving experience. Pain intensity, dose of opioid, mental
      feeling and side effects did not influence the results of the patients.
      CONCLUSION: Psychomotor function and performance are not inevitably impaired in
      patients receiving opioids for pain therapy, but the ranges in the results
      prevent general conclusions. Performance and driving ability must be evaluated
      individually.

PMID- 16086150
TI  - Color vision of the budgerigar (Melopsittacus undulatus): hue matches,
      tetrachromacy, and intensity discrimination.
AB  - Budgerigars, Melopsittacus undulatus, were trained to discriminate monochromatic
      lights from mixtures of two comparison lights. The addition of small amounts of
      UV (365 nm) to blue or yellow lights dramatically changed the color for the
      birds. Hue matches showed the birds to be dichromatic both at long wavelengths
      (only P565 and P508 active) and at short wavelengths (only P370 and P445 active
      because of screening of P508 and P565 by cone oil droplets). In mid-spectrum
      (only P445 and P508 active), a hue match was achieved, but the results were more
      complicated because two opponent neural processes were activated. All observed
      hue matches were in quantitative agreement with calculations of relative quantum
      catch in the pairs of participating single cones and point to the presence of a
      minimum of three opponent neural processes. For the hue matches at mid- and short
      wavelengths, the calculations also predict peak values of absorbance of the cone
      oil droplets associated with P508 and P445. Relative intensity of the training
      light affected difficult matches at long but not short wavelengths, likely due to
      achromatic signals from the double cones. With suitable training, birds could
      make intensity discriminations at short wavelengths, where the double cones have
      diminished sensitivity.

PMID- 16086151
TI  - Moderate approach to the antenatally diagnosed unilateral ureteropelvic junction
      obstruction: experience with 93 patients.
AB  - To evaluate the results of the treatment in patients with antenatally detected
      unilateral ureteropelvic junction obstruction. Ninety-three patients were
      analyzed according to the radiologic and scintigraphic findings and mode of the
      treatment. Fifty-eight patients were treated surgically while 29 patients were
      followed conservatively. All patients were reevaluated at the first year of the
      treatment with diuretic renogram (DR). Follow-up procedure was finished at first
      postoperative year in surgically treated patients, while mean follow-up duration
      was 14.9+/-6.9 months for the conservatively treated group. In the operated
      group, pelvic diameter was greater than 20 mm on ultrasound and overall rate of
      mean split renal function was 38.65+/-9.55% on DR and 39.65+/-12.55% at first
      postoperative year. In the conservatively treated group, mean split renal
      function was 46.17+/-3.42 at the beginning and 47.48+/-4.00 at first year of
      follow-up. Sixty-three percent of the patients underwent pyeloplasty while 83% of
      them were showing obstructive pattern on DR. We believed that surgery should be
      done in renal units which showed pelvic diameter greater than 20 mm and less than
      40% of split renal function, while others might be followed conservatively, with
      or without an obstructive pattern on DR.

PMID- 16086152
TI  - Human scalp dermal papilla and fibrous sheath cells have a different expression
      profile of matrix metalloproteinases in vitro when compared to scalp dermal
      fibroblasts.
AB  - The dermal papilla is a cluster of specialised mesenchymal cells at the bottom of
      the mammalian hair follicle, embedded in a loose extracellular matrix. These
      cells have the capability to induce and support hair growth via close epithelial
      mesenchymal interactions with the keratinocytes surrounding the hair matrix. The
      extracellular matrix of the dermal papilla differs markedly from the
      interfollicular matrix and plays a key role in the maintenance of hair growth. In
      this study we investigated the expression pattern and activity of matrix
      metalloproteinases (MMP) and their tissue inhibitor in in vitro cultures of cells
      derived from scalp dermal papilla and fibrous sheath. Expression and activity of
      MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2 and MT1-MMP were analysed in those
      cells cultured in contact with one of the relevant protein component of the
      dermal matrix, collagen type I as well as in monolayer. Zymographic analysis
      showed activation of MMP-2 in all cells grown in three-dimensional collagen
      lattices whereas MMP-9 was activated only in three-dimensional collagen cultures
      of dermal fibroblasts and weakly in follicular cells. Expression of MMP-1, TIMP
      1, TIMP-2 and MT1-MMP was similar in all cells, in both culture conditions,
      whereas expression of MMP-3 was absent in dermal papilla cells. In addition to a
      series of reported morphological and functional differences between dermal
      fibroblasts and the dermal mesenchyme-derived cells of the hair follicle, we
      reported differences in MMP expression in dermal papilla and fibrous sheath cells
      within the mesenchymal population of the hair follicle.

PMID- 16086153
TI  - Transforming growth factor-beta1 mediated up-regulation of lysyl oxidase in the
      kidneys of hereditary nephrotic mouse with chronic renal fibrosis.
AB  - Lysyl oxidase (LOX), an extracellular enzyme, plays a key role in the post
      translational modification of collagens and elastin, catalyzing inter- and intra
      crosslinking reactions. Because the crosslinked extracellular matrices (ECMs) are
      highly resistant to degradative enzymes, it is considered that the over
      expression of LOX may cause severe fibrotic degeneration. In the present study,
      we addressed the role of LOX-mediated crosslinking in chronic renal
      tubulointerstitial fibrosis using an animal model of hereditary nephrotic
      syndrome, the Institute of Cancer Research (ICR)-derived glomerulonephritis
      (ICGN) mouse. Ribonuclease protection assay (RPA) revealed that LOX mRNA
      expression was up-regulated in the kidneys of ICGN mice as compared with control
      ICR mice. High-level expression of LOX and transforming growth factor (TGF)-beta1
      (an up-regulator of LOX) mRNA was detected in tubular epithelial cells of ICGN
      mouse kidneys by in situ hybridization. Type-I and -III collagens, major
      substrates for LOX, were accumulated in tubulointerstitium of ICGN mouse kidneys.
      The present findings imply that TGF-beta1 up-regulates the production of LOX in
      tubular epithelial cells of ICGN mouse kidneys, and the excessive LOX acts on
      interstitial collagens and catalyzes crosslinking reactions. As a result, the
      highly crosslinked collagens induce an irreversible progression of chronic renal
      tubulointerstitial fibrosis in the kidneys of ICGN mice.

PMID- 16086155
TI  - [An uncommon tumor of the external nose].

PMID- 16086156
TI  - [IMOLA -- a new larynx model for surgical training. Education in transoral laser
      microsurgery of the upper airways].
AB  - BACKGROUND: Education in laser microsurgery is generally acquired under the
      supervision of an experienced surgeon. During training phases, however, increased
      complication rates may occur. Viable models for training are therefore important.
      METHODS: Larynx models should be anatomically accurate in size, form and texture,
      and be able to simulate normal as well as pathological findings. RESULTS: The
      main component is gelatin. Elasticity and thermal qualities can be modified by
      additives. We have been able to develop a synthetic larynx model for CO(2)-laser
      surgery that closely resembles the physical and tactile qualities of human
      tissue. Further modification of the material produced cutting characteristics for
      CO(2)-laser similar to human tissue. CONCLUSION: The new larynx model allows the
      simulation of typical surgical situations. Surgeons in training can practice even
      difficult surgical procedures at low costs and without putting patients at risk,
      before carrying out the procedure on patients.

PMID- 16086157
TI  - Effects of SEA0400 and KB-R7943 on Na+/Ca2+ exchange current and L-type Ca2+
      current in canine ventricular cardiomyocytes.
AB  - SEA0400 and KB-R7943 are compounds synthesised to block transsarcolemmal Na+/Ca2+
      exchange current (I(Na/Ca)); however, they have also been shown to inhibit L-type
      Ca2+ current (I(Ca)). The potential value of these compounds depends critically
      on their relative selectivity for I(Na/Ca) over I(Ca). In the present work,
      therefore, the concentration-dependent effects of SEA0400 and KB-R7943 on
      I(Na/Ca) and I(Ca) were studied and compared in canine ventricular cardiomyocytes
      using the whole-cell configuration of the patch clamp technique. SEA0400 and KB
      R7943 decreased I(Na/Ca) in a concentration-dependent manner, having EC50 values
      of 111+/-43 nM and 3.35+/-0.82 microM, when suppressing inward currents, while
      the respective EC50 values were estimated at 108+/-18 nM and 4.74+/-0.69 microM
      in the case of outward current block. SEA0400 and KB-R7943 also blocked I(Ca),
      having comparable EC50 values (3.6 microM and 3.2 microM, respectively). At
      higher concentrations (10 microM) both drugs accelerated inactivation of I(Ca),
      retarded recovery from inactivation and shifted the voltage dependence of
      inactivation towards more negative voltages. The voltage dependence of activation
      was slightly modified by SEA0400, but not by KB-R7943. Based on the relatively
      good selectivity of submicromolar concentrations of SEA0400--but not KB-R7943-
      for I(Na/Ca) over I(Ca), SEA0400 appears to be a suitable tool to study the role
      of I(Na/Ca) in Ca2+ handling in canine cardiac cells. At concentrations higher
      than 1 microM, however, I(Ca) is progressively suppressed by the compound.

PMID- 16086158
TI  - Localized persistent pulmonary interstitial emphysema in a preterm infant in the
      absence of mechanical ventilation.
AB  - Localized persistent pulmonary interstitial emphysema has rarely been reported in
      preterm infants in the absence of utilization of mechanical ventilation or
      continuous positive airway pressure. The relative rarity of this condition might
      preclude rendering of the correct diagnosis, making patients susceptible to
      unnecessary surgery and increased morbidity and mortality associated with such
      intervention. We present a preterm infant who developed respiratory distress and
      radiographic findings of pulmonary interstitial emphysema on the first day after
      birth, prior to receiving continuous positive airway pressure or mechanical
      ventilation. It is important for radiologists to consider localized persistent
      pulmonary interstitial emphysema in the differential diagnosis of cystic lung
      lesions in preterm infants, even in the absence of mechanical ventilation. In
      cases where there is uncertainty, CT imaging can be useful in making the correct
      diagnosis.

PMID- 16086159
TI  - Extent of myocardial non-compaction: comparison between MRI and echocardiographic
      evaluation.
AB  - BACKGROUND: Non-compaction of the left ventricular myocardium is an important
      cause of cardiomyopathy. There is no clear consensus about its diagnostic
      criteria or the diagnostic test of choice. MRI is increasingly used in the
      pediatric cardiac field because of its superior and objective image quality.
      OBJECTIVE: To compare the echocardiographic and MRI findings in four patients
      with recently diagnosed ventricular non-compaction. MATERIALS AND METHODS: We
      compared the extent of myocardial involvement shown at MRI and echocardiography
      in four individuals, two patients with echocardiographic diagnosis of left
      ventricular non-compaction, and two family members of one of the patients.
      RESULTS: In all patients, MRI showed wider area of involvement than
      echocardiography. A definite diagnosis was entertained in only two patients by
      echocardiography but in all by MRI. Cine imaging was diagnostic of the disease in
      all patients. Black-blood pool imaging with double-inversion recovery sequence
      also helped to visualize the abnormal areas by showing slow flow artifacts in the
      four- and two-chamber images. CONCLUSION: MRI provided better delineation of the
      extent of the abnormal trabeculation in patients with non-compaction of the left
      ventricular myocardium. It was particularly useful when the myocardial
      involvement was subtle, as in the asymptomatic family members.

PMID- 16086160
TI  - Tracer development and hybrid imaging.

PMID- 16086161
TI  - Absorbed whole-body doses from whole-body CT scan examinations: can the
      observations relating to screening of healthy individuals be extrapolated to the
      use of whole-body CT in PET/CT hybrid machines?

PMID- 16086162
TI  - Viral evasion of the MHC class I antigen-processing machinery.
AB  - In their adaptation to the immune system in vertebrates, viruses have been forced
      to evolve elaborate strategies for evading the host's immune response. To ensure
      life-long persistence in the host, herpes viruses, adenoviruses and retroviruses
      have exploited multiple cellular pathways for their purpose, including the class
      I antigen-processing machinery. Attractive and prominent targets for viral
      attacks are the proteasome complex, the transporter associated with antigen
      processing, and MHC class I molecules. This review briefly outlines the different
      mechanisms of viral interference with the antigen-presentation pathway.

PMID- 16086163
TI  - Sleep symptoms and clinical markers of illness in patients with heart failure.
AB  - The purpose of this study was to survey patients with heart failure (HF) for
      sleep symptoms using a standardized questionnaire and correlate symptoms with
      conventional markers of clinical status. A self-report paper questionnaire was
      offered to patients presenting to a tertiary care HF clinic. Symptoms were
      grouped according to "risk" categories and correlated with routine clinical
      information. One hundred six (52.7% of 201 with all data) respondents had a high
      pretest probability for sleep apnea syndrome. Sixty three (31.3%) reported
      symptoms suggesting the presence of chronic insomnia; seven (3.5%) and eight (4%)
      reported symptoms of narcolepsy and restless legs syndrome, respectively. High
      risk respondents for sleep apnea had a higher body mass index (p<0.001), were
      younger (p<0.05), and had a higher ejection fraction (p<0.05). The odds ratio
      (confidence interval) for paroxysmal nocturnal dyspnea (PND) to a complaint of
      sleepiness was 1.99 (1.1-3.6) and to a complaint of insomnia was 3.5 (1.8-6.5).
      In men, complaints of sleepiness in patients with PND were correlated, 4.47 (1.9
      10.3), as was a correlation to high pretest probability for sleep apnea, 2.47
      (1.1-5.5). There were no correlation of New York Heart Association status
      classification to high risk for sleep apnea, but a complaint of insomnia tended
      to occur with worsening functional status (p<0.05). There was only modest
      correlation of self-reported symptoms as elicited by a questionnaire and risk for
      sleep disorders with common clinical assessments for HF. Such collection of
      symptoms might be useful in establishing guidelines for routine sleep testing or
      as an adjunct to clinical trials.

PMID- 16086165
TI  - Host physiological condition regulates parasitic plant performance: Arceuthobium
      vaginatum subsp. cryptopodum on Pinus ponderosa.
AB  - Much research has focused on effects of plant parasites on host-plant physiology
      and growth, but little is known about effects of host physiological condition on
      parasite growth. Using the parasitic dwarf mistletoe Arceuthobium vaginatum
      subsp. cryptopodum (Viscaceae) and its host Pinus ponderosa, we investigated
      whether changes in host physiological condition influenced mistletoe shoot
      development in northern Arizona forests. We conducted two studies in two
      consecutive years and used forest thinning (i.e., competitive release) to
      manipulate host physiological condition. We removed dwarf mistletoe shoots in
      April, before the onset of the growing season, and measured the amount of
      regrowth in the first season after forest thinning (Study I: n=38 trees; Study
      II: n=35 trees). Thinning increased tree uptake of water and carbon in both
      studies, but had no effect on leaf N concentration or delta13C. Mistletoe shoot
      growth was greater on trees with high uptake of water and carbon in thinned
      stands than trees with low uptake in unthinned stands. These findings show that
      increased resource uptake by host trees increases resources to these
      heterotrophic dwarf mistletoes, and links mistletoe performance to changes in
      host physiological condition.

PMID- 16086166
TI  - Partitioning mechanisms of predator interference in different habitats.
AB  - Prey are often consumed by multiple predator species. Predation rates on shared
      prey species measured in isolation often do not combine additively due to
      interference or facilitation among the predator species. Furthermore, the
      strength of predator interactions and resulting prey mortality may change with
      habitat type. We experimentally examined predation on amphipods in rock and algal
      habitats by two species of intertidal crabs, Hemigrapsus sanguineus (top
      predators) and Carcinus maenas (intermediate predators). Algae provided a safer
      habitat for amphipods when they were exposed to only a single predator species.
      When both predator species were present, mortality of amphipods was less than
      additive in both habitats. However, amphipod mortality was reduced more in rock
      than algal habitat because intermediate predators were less protected in rock
      habitat and were increasingly targeted by omnivorous top predators. We found that
      prey mortality in general was reduced by (1) altered foraging behavior of
      intermediate predators in the presence of top predators, (2) top predators
      switching to foraging on intermediate predators rather than shared prey, and (3)
      density reduction of intermediate predators. The relative importance of these
      three mechanisms was the same in both habitats; however, the magnitude of each
      was greater in rock habitat. Our study demonstrates that the strength of specific
      mechanisms of interference between top and intermediate predators can be
      quantified but cautions that these results may be habitat specific.

PMID- 16086167
TI  - Mechanisms of selectivity in a nocturnal fish: a lack of active prey choice.
AB  - Fish that feed on individual zooplankton usually exhibit strong selectivity for
      large prey. Such selectivity can result from the predator's active choice of
      larger prey or from differential encounter rate due to lower detectability of
      small prey, or both. In diurnal fishes, selectivity is thought to be determined
      mostly by active choice. In spite of a lack of direct observations, active choice
      is also considered the prevailing mechanism of prey selectivity in nocturnal
      fishes. Our objective was to resolve this mechanism in the highly selective,
      nocturnal zooplanktivorous fish Apogon annularis. Laboratory experiments
      indicated that the fish's encounter rate with small prey was lower than that with
      large prey and that its selectivity became stronger with decreasing light
      intensity. Feeding efficiency, defined as the ratio between feeding and encounter
      rates, ranged 41-89% and was positively correlated with prey size. When feeding
      on a mixture of prey sizes, the fish fed on each size group at a rate similar to
      that of its feeding on the respective size alone, indicating that selectivity in
      A. annularis was due to size-dependent encounter rate and differential feeding
      efficiency. A low visual acuity in A. annularis, as inferred from its inability
      to detect small prey (<0.9 mm in length), together with the low abundance of
      large zooplankton in situ, can explain the dominance of differential encounter
      over active choice in this nocturnal coral-reef fish.

PMID- 16086168
TI  - Indirect interaction between two native thistles mediated by an invasive exotic
      floral herbivore.
AB  - Spatial and temporal variation in insect floral herbivory is common and often
      important. Yet, the determinants of such variation remain incompletely
      understood. Using 12 years of flowering data and 4 years of biweekly insect
      counts, we evaluated four hypotheses to explain variation in damage by the
      Eurasian flower head weevil, Rhinocyllus conicus, to the native North American
      wavyleaf thistle, Cirsium undulatum. The four factors hypothesized to influence
      weevil impact were variations in climate, weevil abundance, phenological
      synchrony, and number of flower heads available, either on wavyleaf thistle or on
      the other cooccurring, acquired native host plant (Platte thistle, Cirsium
      canescens), or on both. Climate did not contribute significantly to an
      explanation of variation in R. conicus damage to wavyleaf thistle. However,
      climate did influence weevil synchrony with wavyleaf flower head initiation, and
      phenological synchrony was important in determining R. conicus oviposition levels
      on wavyleaf thistle. The earlier R. conicus was active, the less it oviposited on
      wavyleaf thistle, even when weevils were abundant. Neither weevil abundance nor
      availability of wavyleaf flower heads predicted R. conicus egg load. Instead, the
      strongest predictor of R. conicus egg load on wavyleaf thistle was the
      availability of flower heads on Platte thistle, the more common, earlier
      flowering native thistle in the sand prairie. Egg load on wavyleaf thistle
      decreased as the number of Platte thistle flower heads at a site increased. Thus,
      wavyleaf thistle experienced associational defense in the presence of flowering
      by its now declining native congener, Platte thistle. These results demonstrate
      that prediction of damage to a native plant by an exotic insect may require
      knowledge of both likely phenological synchrony and total resource availability
      to the herbivore, including resources provided by other nontarget native species.

PMID- 16086169
TI  - [Utilizing optical coherence tomography (OCT) for visualization of urothelial
      diseases of the urinary bladder].
AB  - PURPOSE: The technique of optical coherence tomography (OCT) has significantly
      improved over the last few years. This new diagnostic procedure allows imaging of
      tissue structure of the bladder wall during cystoscopy with high resolution.
      MATERIALS AND METHODS: The penetration depth of OCT is limited to 2.5 mm. The
      resolution is approximately 15 microm. Fifty patients with different clinical
      conditions of the bladder were examined. Altogether 488 OCT images were
      generated. RESULTS: OCT of normal bladder mucosa clearly shows a differentiation
      between urothelium, lamina propria, and smooth muscle. Cystitis and metaplasia
      are characterized by blurring of the laminated structure and thickening of the
      epithelial layer. In malignant areas there is complete loss of the regular
      layered tissue structure. CONCLUSION: OCT improves the diagnosis of flat lesions
      of the urothelium. It has the potential for facilitating intraoperative staging
      of malignant areas in the bladder.

PMID- 16086170
TI  - [Modern ultrasound technologies and their application in pediatric urinary tract
      imaging].
AB  - In children ultrasound plays a central role in the diagnostic imaging of the
      urinary tract. It is used most frequently and as a primary diagnostic option.
      Consequently, innovations in ultrasound technology and ultrasound contrast media
      have major impact on pediatric urosonography. Harmonic imaging is a modality that
      produces artifact-free images with high resolution. It has been shown that
      harmonic imaging is superior to fundamental mode in many urosonographic
      indications. Color Doppler is an established imaging modality, but its
      application for diagnosis of stones in the urinary tract, especially in children,
      is relatively new. The so-called twinkling sign, a color Doppler artifact at the
      site where one normally expects the acoustic shadow to be, enhances the
      conspicuity of the stone. A further development is three-dimensional (3D)
      ultrasound. It offers better volume measurement of the bladder and kidneys than
      2D ultrasound. Contrast-enhanced voiding urosonography has already proven to be a
      valuable alternative in the diagnosis of vesicoureteral reflux. Thus, a
      significant decrease of radiation exposure has become possible as it replaces the
      radiological methods. With the introduction of contrast-specific ultrasound
      imaging modalities, further improvements in voiding urosonography are emerging.

PMID- 16086171
TI  - Serological and molecular diversity in the cattle MHC class I region.
AB  - Information on major histocompatibility complex (MHC) diversity in cattle is
      important to aid our understanding of immune responses and may contribute to
      maintenance of healthy cattle populations. Equally, understanding the mechanisms
      involved in generating this diversity may shed light on the complex nature of
      mammalian MHC evolution. The aim of this study was to assess molecular and
      serological variation within cattle MHC class I molecules and to study the
      mechanisms generating diversity. To address this aim, sequence variation was
      examined in 12 serologically assigned alleles from three putative loci and
      correlated with monoclonal antibody (mAb) binding data. The results demonstrate
      that both alloantisera and mAbs often fail to distinguish gene products that
      differ by a significant number of amino acids. Conversely, some mAbs could
      distinguish alleles differing by only one or two amino acids. Examination of the
      sequences demonstrates sharing of motifs between alleles, some encoded at
      distinct loci, supporting the occurrence of interlocus recombination within the
      cattle MHC class I region. The implications of this for MHC sequence diversity,
      and functional capability, are discussed.

PMID- 16086172
TI  - Reliability of statistical associations between genes and disease.
AB  - Many statistical associations between a disease and alleles of specific genes
      have proven to be irreproducible. In part, this irreproducibility can be
      attributed to a lack of replication before publication and the fact that, until
      recently, the relationship between statistical significance and various measures
      of reproducibility was not widely understood. This review proposes a
      classification system, the Better Associations for Disease and GEnes (BADGE)
      system, for describing genetic associations. The BADGE classes, first class
      through fifth class, are based on the P value of the association. A first-class
      association, with P < 2 x 10(-7), is expected to be reproducible even in the
      absence of other evidence supporting the association. A fifth-class association
      corresponds to conventional statistical significance (P < 5 x 10(-2)), which
      provides almost no assurance of reproducibility. Three intervening classes,
      described as second-, third-, and fourth-class associations, are defined by P
      values separated by factors of 20 or 25 from these extremes.

PMID- 16086173
TI  - Common silent mutations in all types of hereditary complement C1q deficiencies.
AB  - Hereditary complete deficiency of complement component C1q is a rare genetic
      disorder that is associated with severe recurrent infections and a high
      prevalence of lupus-erythematosus-like symptoms. In the past, several single
      nucleotide polymorphisms have been identified in all three genes coding for the
      C1q A, B, and C chains. These point mutations which either lead to termination
      codons, frameshift, or amino acid exchanges were thought to be responsible for
      these defects as no other nonsense or missense mutations were found. As a result
      of the aberrations, either a nonfunctional C1q antigen is present or no C1q
      protein is detectable in the patients' sera. Screening 46 individuals from seven
      families with different forms of C1q deficiencies identified a homologous silent
      mutation at position Gly70 (GGG > GGA) of the C1q A gene of all 11 C1q-deficient
      patients. A high number of family members that were heterozygous for the coding
      mutations carried the silent mutation in the homozygous (18%) or heterozygous
      (36%) state. In addition to the Gly70 mutation in the A gene, another homozygous
      silent mutation (C gene at position Pro14, CCT >CCC) was detected in all C1q
      deficient patients.

PMID- 16086174
TI  - Characterization of Toll-like receptor 3 gene in rainbow trout (Oncorhynchus
      mykiss).
AB  - Antiviral immunity in fish is not well understood. In mammals, Toll-like receptor
      (TLR) 3 is involved in double-stranded RNA recognition and host immune response
      activation. Here, we report the first identification of a rainbow trout TLR3
      ortholog (rtTLR3), its genomic structure, and mRNA regulation. Six exons and five
      introns were identified from bacterial artificial chromosome (BAC) and expressed
      sequence tag (EST) sequencing, and this genomic organization is similar to
      mammalian and fish TLR3 genes. The putative 913 amino acid protein has a
      Toll/interleukin (IL)-1R (TIR) domain, a transmembrane domain, and leucine-rich
      repeats. In healthy trout, rtTLR3 is highly expressed in the liver, pyloric ceca,
      intestine, spleen, and anterior and trunk kidney tissues. To investigate whether
      rtTLR3 is involved in antiviral immunity, transcriptional regulation in vivo was
      examined by quantitative real-time polymerase chain reaction (PCR) after poly
      inosinic:cytidylic (I:C) and infectious hematopoietic necrosis virus (IHNV)
      treatments. TLR3 mRNA expression peaked 1 day after poly (I:C) injection of live
      animals, while the peak of gene expression after live IHNV challenge was observed
      on day 3. In vitro stimulation of rainbow trout anterior kidney leukocytes with
      poly (I:C) also enhanced rtTLR3 expression. Up-regulation was specific to viral
      challenge as there was no significant up-regulation of rtTLR3 mRNA levels in the
      spleen and a modest down-regulation in the anterior kidney after bath challenge
      with a gram-negative bacterial trout pathogen, Yersinia ruckeri. The sequence
      conservation of trout TLR3 and mRNA regulation after poly (I:C) or RNA virus
      exposures strongly suggest a role for trout TLR3 in antiviral immunity.

PMID- 16086175
TI  - Isolation and characterization of drought-related trehalose 6-phosphate-synthase
      gene from cultivated cotton (Gossypium hirsutum L.).
AB  - Due to the important role of cotton drought-tolerant varieties and the reported
      involvement in this trait of trehalose-6-phosphate-synthase, the respective gene
      (TPS) was isolated and characterized from cultivated cotton, Gossypium hirsutum
      (ZETA 2 cultivar), using a chromosome-walking technique. TPS has three exons
      comprising the coding region. Southern blot analysis indicated that the Gossypium
      genomes (A and D) contain a single copy of TPS per genome. In addition, the
      expression of this gene was studied in different plant tissues. Plants of the
      Australian cotton variety Siokra L23, known for its drought tolerance, were
      subjected to drought stress (using PEG 6,000 solution, for 4 h during the dark
      period of the day and for four consecutive days); leaves, stems and roots were
      collected after the end of the stress period. Total extracted RNA was examined
      for the presence of transcripts, in the above-mentioned tissues of stressed and
      well-watered plants, by reverse transcription-polymerase chain reaction (RT-PCR).
      The expression levels, determined semi-quantitatively, indicated that the gene
      was expressed in all plant tissues under both water availability conditions.
      However, increased expression levels of TPS were observed mainly in stressed
      leaves and roots compared to those of the well-watered control. This finding is
      in agreement with the fact that TPS participates in trehalose biosynthesis, known
      for its participation in stress signal transduction in higher plants.

PMID- 16086176
TI  - A gene locus for progressive familial heart block type II (PFHBII) maps to
      chromosome 1q32.2-q32.3.
AB  - Cardiac conduction defects that are associated with dilated cardiomyopathy (DCM)
      are generally considered to be sporadic clinical entities, although familial
      forms of disorders with these clinical features have been identified in a number
      of families in different countries. An autosomal dominant cardiac disorder
      characterised by conduction abnormalities and DCM, termed progressive familial
      heart block type II (PFHBII) (OMIM 140400), has been described in a South African
      Caucasian family of Northern European descent. Known candidate loci for isolated
      conduction disorders, isolated DCM and conduction disorders complicated by DCM
      were excluded from disease causation in this family by linkage analysis, with the
      exception of the DCM-associated (CMD1D) locus on chromosome 1q32, where a maximum
      multipoint lod score of 3.7 in the interval between D1S3753 and D1S414, was
      generated. This region encompassed the troponin T gene (TNNT2), however, genetic
      fine mapping and haplotype analysis excluded TNNT2 as cause of PFHBII and placed
      the disease-causative gene within a 3.9 cM (2.85 Mb) interval, flanked by D1S70
      and D1S505. Analysis of KCNH1, KIAA0205, LAMB3 and PPP2R5A, which map within the
      critical interval, indicated that the PFHBII-causative mutation does not lie
      within the coding regions or splice junctions of these plausible candidate genes.
      The data indicate the existence of a novel locus involved in the pathogenesis of
      cardiac conduction abnormalities and DCM.

PMID- 16086177
TI  - Evaluation of lacrimal fluid as an alternative for monitoring glucose in
      critically ill patients.
AB  - OBJECTIVE: This study evaluated the use of lacrimal fluid glucose concentrations
      as a minimally invasive, alternative sampling strategy for monitoring glucose
      concentrations in surgical/trauma ICU patients. DESIGN AND SETTING: Prospective,
      paired sample study in an adult surgical/trauma ICU. PATIENTS: Patients receiving
      subcutaneous or intravenous insulin requiring routine capillary blood glucose
      measurements. Patients receiving ocular lubricants, artificial tears, or
      routinely administered ophthalmic medications and patients with facial injuries
      were excluded. INTERVENTIONS: Lacrimal fluid was collected using glass capillary
      tube placed near the cul-de-sac of the eye. Capillary blood glucose was
      determined using a bedside glucose meter as per routine ICU care. MEASUREMENTS
      AND RESULTS: Lacrimal fluid glucose concentration was analyzed using high
      performance liquid chromatography with pulse amperometric detection. Forty-four
      paired samples from five patients were analyzed. Pearson correlation between
      lacrimal fluid (microM) and blood glucose (mM) concentrations and the
      proportional change from baseline revealed no significant associations. Due to
      the very poor association, enrollment was discontinued after five patients.
      CONCLUSIONS: Lacrimal fluid and blood glucose concentrations were poorly
      correlated, suggesting that the former is not a reliable alternative to blood
      glucose monitoring in surgical/trauma ICU patients requiring insulin therapy.

PMID- 16086179
TI  - Validation of portal vein flow measurement by color flow Doppler sonography in a
      porcine model of septic shock.
AB  - OBJECTIVE: To compare portal vein flow values gained by color flow Doppler
      sonography with simultaneously derived data from an ultrasound transit time flow
      probe. DESIGN: Repeated, simultaneous flow measurements were performed in a
      prospective study investigating the effect of various drugs on hepatosplanchnic
      perfusion and energy balance in a long-term model of stable, hyperdynamic
      endotoxin shock. SETTING: Investigational animal laboratory. SUBJECTS: Domestic
      pigs. INTERVENTIONS: Alterations in respirator setting were studied with regard
      to their effect on the quality of color flow Doppler data in comparison to flow
      probe data. Additional experiments included variation in PEEP level in
      conjunction with volume resuscitation. MEASUREMENTS AND RESULTS: Respiratory
      rates of 14-18/min led to color Doppler flow values consistently 20-40% above
      simultaneously measured flow probe data. Temporary apnea led to enhanced
      agreement of data. Reduction in respiratory rate to 8/min with increase in tidal
      volume consistently led to color Doppler data within 10% of the corresponding
      flow probe values. CONCLUSIONS: A short-term period of respirator-dependent,
      constant portal vein inflow enables color Doppler sonography to detect correct
      values in a clinically relevant setting of hyperdynamic endotoxin shock.

PMID- 16086178
TI  - Statin therapy prior to ICU admission: protection against infection or a severity
      marker?
AB  - OBJECTIVE: Examine the impact of previous statin therapy on hospital mortality
      and whether it is due to a protective effect against ICU-acquired infections.
      DESIGN AND SETTING: Cohort comparison study by retrospective chart-based analysis
      in a 26-bed, university-affiliated, medical-surgical ICU. PATIENTS: We analyzed
      data from 438 patients at high risk of ICU-acquired infections, i.e., those
      receiving mechanical ventilation for more than 96 h, 38 (8.7%) of whom had been
      treated with statins prior to and during ICU admission. MEASUREMENTS AND RESULTS:
      We recorded clinical characteristics, number and type of ICU-acquired infections,
      and ICU and hospital mortality. Statin-treated patients were older (71.7+/-8.3
      vs. 61.5+/-18.3 years), but differences in predicted mortality risk by APACHE II
      (39.5+/-24.7 vs. 35.8+/-24.3%) did not reach statistical significance. The ICU
      acquired infection rate in statin-treated patients was nonsignificantly lower
      (29% vs. 38%) and delayed (median 12 vs.10 days), without differences regarding
      the source of infections. Nevertheless, hospital mortality was significantly
      higher in statin-treated patients (61% vs. 42%), even after adjustment for APACHE
      II predicted risk (observed/expected ratio 1.53 vs. 1.17). CONCLUSIONS: Statin
      therapy is associated with worse outcome, probably because underlying clinical
      conditions are insufficiently considered in mortality predictors. Its presumed
      protective effect against ICU infections remains unconfirmed.

PMID- 16086180
TI  - Anaplastic large-cell lymphoma primarily infiltrating femoral muscles.

PMID- 16086181
TI  - Value of axial and coronal maximum intensity projection (MIP) images in the
      detection of pulmonary nodules by multislice spiral CT: comparison with axial 1
      mm and 5-mm slices.
AB  - The purpose of this study was to investigate the diagnostic accuracy of non
      overlapping 10-mm axial and coronal maximum intensity projections (MIP) in
      comparison with standard axial 1-mm and 5-mm slices in the detection of pulmonary
      nodules. Sixty patients with suspected nodules who underwent multislice spiral CT
      of the chest were evaluated. Axial 1-mm and 5-mm slices as well as non
      overlapping 10-mm axial/coronal MIPs were interpreted independently by three
      blinded radiologists. After initial review, a retrospective consensus session was
      performed for agreement on final nodule counts using the axial 1-mm slices as
      gold standard. Small nodules of less than 5 mm in size were most accurately
      detected by the axial MIPs. Receiver operating characteristic (ROC) analysis of
      these small nodules showed that 5-mm slices were not capable of a statistically
      significant differentiation of nodules from other focal lesions in two observers
      (p=0.034 and p=0.012, respectively) whereas 1-mm slices and coronal/axial MIPs
      did allow a statistically significant differentiation in all observers (p<0.001).
      Nodules larger than 5 mm were equally well depicted with all modalities. Non
      overlapping 10-mm axial MIPs improve the accuracy in the detection of small
      pulmonary nodules.

PMID- 16086182
TI  - Adrenal glands in beta-thalassemia major: magnetic resonance (MR) imaging
      features and correlation with iron stores.
AB  - This study aimed at describing the magnetic resonance (MR) imaging features of
      the adrenal glands in beta-thalassemic patients and at investigating the relation
      between adrenal and hepatic siderosis. Adrenal signal intensity (SI) was
      retrospectively assessed on abdominal MR studies of 35 patients with beta
      thalassemia major undergoing quantification of hepatic siderosis and 12 healthy
      controls, using T1-(120/4/90), intermediate-(120/4/20), and T2*-(120/15/20)
      weighted GRE sequences. Adrenal SI was graded as grade 0 (normal SI on all
      sequences), grade 1 (hypointensity on T2* alone), or grade 2 (hypointensity on at
      least T2*). Adrenal size was measured in the thalassemic patients and compared
      with normative data. Liver-to-muscle (L/M) SI ratios, expressing hepatic
      siderosis, were estimated on each sequence. Serum ferritin levels were recorded.
      Adrenal hypointensity (grades 1 and 2) was noted in 24/35 (68.6%) patients. L/M
      ratios correlated significantly with adrenal SI in all sequences. Patients with
      grade 1 and grade 2 adrenal SI had significantly decreased L/M ratios compared
      with grade 0. Serum ferritin correlated significantly with L/M values but not
      with adrenal SI. Adrenal size was within normal limits. Diffuse hypointensity in
      normal-sized adrenals is a common MR finding in beta-thalassemic patients and
      correlates with the degree of hepatic siderosis.

PMID- 16086184
TI  - The Gem interacting protein (GMIP) gene is associated with major depressive
      disorder.
AB  - Major depressive disorder (MDD) is a mood disorder with a significant heritable
      component. Structural neuronal impairment has been considered to be implicated in
      MDD, as it leads to brain morphological alterations such as hippocampal atrophy.
      The Gem interacting protein, GMIP, is a novel Rho GTPase-activating protein known
      to play important roles in neurite growth and axonal guidance. We examined the
      GMIP gene for possible association in a Japanese sample of 164 patients with MDD
      and 164 controls matched for sex. We found a significant association with MDD for
      one single nucleotide polymorphism (SNP) (-525G/A) located on the 5'-upstream
      region of the GMIP gene (p=0.039, odds ratio 1.66, 95% CI 1.05-2.69) and stronger
      evidence for association in a multimarker haplotype analysis (p=0.004). We then
      performed a promoter-luciferase reporter assay; the promoter activity for -525A
      allele, which was in excess in the MDD patients, was significantly decreased
      compared with the -525G allele in transient transfection experiments using three
      types of cell lines. Our results suggest that genetic variations in the GMIP gene
      can confer susceptibility to MDD, and the associated promoter SNP might play a
      role in the transcriptional regulation of the GMIP gene. Further study needs to
      be undertaken to validate the association between the GMIP gene and MDD.

PMID- 16086183
TI  - Apoptosis in infectious disease: how bacteria interfere with the apoptotic
      apparatus.
AB  - Cell death by apoptosis is a common response of a human cell to many extrinsic
      stimuli. A cell's sensitivity to apoptotic triggers is affected by its activation
      and differentiation status. Bacteria are recognised by cellular receptors and
      elicit a multitude of signal transduction events that can, among other effects,
      alter the cell's response towards apoptotic stimuli. Many different bacteria and
      bacterial products have been recognised as agents that can act in this way and
      either induce or inhibit cell death. Besides these common and, as we argue,
      indirect activities, chlamydiae have been described to have a more specific
      capacity. These specialists of intracellular life can directly attack the host
      cell's apoptotic pathway. Here, we will attempt to structure the field of
      bacterial inhibition of apoptosis and discuss recent advancements in our
      knowledge of how chlamydiae interfere with the host cell's capacity to undergo
      apoptosis.

PMID- 16086185
TI  - X-linked creatine transporter deficiency: clinical description of a patient with
      a novel SLC6A8 gene mutation.
AB  - Creatine transporter deficiency is an X-linked disorder characterized by mental
      retardation and language delay. The authors report a patient affected by creatine
      transport deficiency caused by a novel mutation in the SLC6A8 gene. Impairment in
      social interaction represents a consistent clinical finding in the few cases
      described to date and may be a diagnostic clue for creatine transporter
      deficiency in males affected by mental retardation, seizures, and language
      impairment.

PMID- 16086186
TI  - Differential expression of splice variant and wild-type parkin in sporadic
      Parkinson's disease.
AB  - BACKGROUND: Altered splicing of parkin under cellular stress could lead to
      changes in gene expression and altered protein activity. The causative role of
      parkin in sporadic Parkinson's disease (PD) is unknown. OBJECTIVES: We described
      a parkin splice variant (SV) in the substantia nigra and leukocytes of sporadic
      PD patients. Using a case control methodology, we investigated the exon 4 SV
      (E4SV) and wild-type parkin expression in the leukocytes of sporadic PD patients
      and healthy individuals. METHODS/RESULTS: We identified a parkin E4SV in the
      substantia nigra and leukocytes of sporadic PD patients and controls by reverse
      transcriptase-polymerase chain reaction (PCR). The exon 4 (122 bp) deletion
      resulted in a reading frame shift over the junction of exons 3-5 and a stop codon
      (tga) 17 bp downstream from exon 3. The translated truncated protein was
      associated with a total loss of the two-RING finger functional domain. Utilizing
      TaqMan real-time PCR with probes located across the junction of exons 3-4 or 3-5,
      we demonstrated an over-expression of E4SV/wild-type parkin ratio in the
      leukocytes of sporadic PD patients compared to age-, gender-, and race-matched
      controls (p<0.0005). A multivariate regression analysis demonstrated that the
      ratio of E4SV/wild-type parkin expression increased with age in PD patients, but
      this was not observed in the controls (p<0.0005). CONCLUSION: The relative
      expression of E4SV/wild type parkin was increased in sporadic PD compared to
      healthy controls. Based on our observations, further functional studies to
      determine the pathophysiologic role of E4SV in sporadic PD patients will be of
      importance.

PMID- 16086187
TI  - A global resource for computational chemistry.
AB  - A modular distributable system has been built for high-throughput computation of
      molecular structures and properties. It has been used to process 250,000
      compounds from the NCI database and to make the results searchable by structures
      and properties. The IUPAC/NIST InChI specification and algorithm has been used to
      index the structures and enforce integrity during computation. A number of novel
      features of the PM5 Hamiltonian were identified as a result of the high
      throughput approach. The system and the data can be redistributed and reused and
      promote the value of computed data as a primary chemical resource.

PMID- 16086188
TI  - The cost of being an omnivore: mandible wear from plant feeding in a true bug.
AB  - Evolutionary and ecological transitions from carnivorous to omnivorous feeding
      may be constrained by the ability of the animal to cope with disparate types of
      foods, even if preadaptations for such behaviour exist. The omnivorous true bug,
      Dicyphus hesperus (Hemiptera: Miridae) requires both animals (small, soft-bodied
      insects) and plants in its diet and obtains the majority of its dietary and
      metabolic water from plant feeding. Serrations on the lateral margins of the
      mandibular stylets wear with age, and this wear is exacerbated when the insects
      feed on plants compared to those provided free water and no plants. D. hesperus
      that feed on plants attack fewer prey but consumed similar amounts of prey tissue
      compared to individuals that were provided free water. Although others have shown
      mandible wear for plant-chewing animals we show for the first time that plant
      feeding can impose similar wear on plant-piercing animals as well.

PMID- 16086190
TI  - Instability helps virtual flies to mate.
AB  - In this paper we perform a bifurcation analysis for a discrete time dynamical
      system, describing the behavior of a virtual fly, developed by Boddeker and
      Egelhaaf (2003). Like real blowflies, the virtual counterparts exhibit a
      dichotomous behavior: they catch small targets but follow big objects at a
      constant distance. We consider this model for targets on linear and on circular
      trajectories. Then we transform the system into a ''frozen'' form, such that the
      position of the target is fixed. It turns out that the loss of stability of a
      fixed point in the frozen system due to a Neimark-Sacker bifurcation, explains
      the dichotomous behavior of the virtual fly.

PMID- 16086189
TI  - Insufficiency risk of esophagojejunal anastomosis after total abdominal
      gastrectomy for gastric carcinoma.
AB  - BACKGROUND: The outcome and quality of surgical treatment in gastric cancer are
      closely associated with specific postoperative morbidity and mortality, in
      addition to an oncosurgically adequate resection status. In this context, a
      preventive concept of decreasing the insufficiency rate of esophageal anastomosis
      may have a great impact. METHOD: Over a time period of 12 months (from 1 January
      2002 to 31 December 2002), 1,199 patients (from 80 East German hospitals) with
      gastric carcinoma, carcinoma of the esophagogastral junction, or gastrointestinal
      stroma tumor (GIST) were enrolled in this prospective multicenter observational
      study with the aim of evaluating their early postoperative outcome. By means of a
      logistic regression analysis, independent variables, which alter significantly
      the healing of esophagojejunal anastomosis, were determined; in addition, their
      clinical impact on preventive management to lower the insufficiency rate of
      esophageal anastomosis was investigated. RESULTS: In 1,139 patients, histological
      investigation revealed gastric carcinoma. Out of these patients, 1,031 subjects
      underwent surgical intervention (90.5%) and 891 individuals underwent resection
      (86.4%). In 813 patients, radical resection (subtotal resection and gastrectomy)
      was executed (78.9%), whereas in 726 cases, R(0) resection was achieved (81.5%).
      Gastrectomy was the preferred procedure in 649 patients, resulting in a
      gastrectomy rate of 62.9% relating to all patients who underwent operation
      (curative and palliative intention, 80.3% and 19.7%, respectively). The
      insufficiency rate of esophagojejunal anastomosis was 5.7% (37/649). Neither the
      comparison between the various procedures for the reconstruction of the
      esophagojejunal passage and anastomosing techniques after gastrectomy nor that
      between gastrectomies with curative and palliative intention revealed any
      significant difference. Dysphagia and gastric outlet syndrome due to a stenosis
      were determined as independent variables by a logistic regression analysis of all
      preoperative and intraoperative variables. In all patients with gastric
      carcinoma, both parameters were recorded in 9.9% (113/1,139) and 6.7% (76/1,139),
      respectively. CONCLUSION: Dysphagia and gastric stenosis, which significantly
      influence the healing of esophagojejunal anastomosis after gastrectomy, are
      considered characteristics of an advanced tumor growth and a pretherapeutic lack
      of an adequate nutrition. This emphasizes the necessity of an early diagnosis of
      gastric cancer in order to lower perioperative morbidity. In addition, dysphagia
      is commonly associated with an obstruction of the upper gastrointestinal tract,
      which can lead to nutritional deficits, and thus deserves specific care during
      preventive management.

PMID- 16086192
TI  - [Influence of physical activity on human health].
AB  - The lack of physical activity -- frequently associated with malnutrition -- has
      led to a dramatic increase of so-called diseases of civilization in industrial
      nations. Hereby -- apart from the cardiovascular diseases -- in particular
      disorders of carbohydrate and lipid metabolism as well as the musculoskeletal
      system are included. Physical inactivity can be considered a proven risk factor
      for these diseases. Children and adolescents are increasingly affected. In the
      development of effective preventive strategies, the enhancement of
      physical/sportive activities in everyday life as well as with in the framework of
      systematic health-orientated training plays a central role. This is confirmed by
      an abundance of scientific studies indicating that regular physical activity has
      anenormous potential with regard to the physical and psychological health
      maintenance in all life phases. The underlying biological mechanisms are complex
      and affect almost all human organic systems. Yet, the health benefit is
      critically dependent upon the form, duration and intensity. Endurance-orientated
      activities such as walking, running, cycling etc. performed at a moderate
      intensity, exercised at least 2 days a week for a duration of 30-60 min, are
      recommended. This should be supplemented by moderate strength training comprising
      all relevant muscle groups. An early commencement of regular, continuous,
      lifelong physical activities is particularly effective and can be, thus,
      recommended from a health-orientated perspective.

PMID- 16086193
TI  - [Exercise therapy as a therapeutic concept].
AB  - Lack of exercise is a primary cause for today's level of morbidity and mortality
      in the Western world. Thus, exercise as a therapeutic modality has an important
      role. Beneficial effects of exercise have been extensively documented,
      specifically in primary and secondary prevention of coronary heart disease (CHD),
      diabetes mellitus, hypertension, disorders of fat metabolism, heart
      insufficiency, cancer, etc. A regular (at least 3 x per week) endurance training
      program of 30-40 min duration at an intensity of 65-70% of VO(2)max involving
      large muscle groups is recommended. The specific exercise activity can also
      positively affect individuals with orthopedic disease patterns, i.e.,
      osteoporosis, back pain, postoperative rehabilitation, etc. Endurance strength
      training in the form of sequential training involving approx. 8-10 different
      exercises for the most important muscle groups 2 x per week is a suitable
      exercise therapy. One to three sets with 8-12 repetitions per exercise should be
      performed until volitional exhaustion of the trained muscle groups among healthy
      adults and 15-20 repetitions among older and cardiac patients. Apart from a
      positive effect on the locomotor system, this type of strength training has
      positive effects on CHD, diabetes mellitus, and cancer.

PMID- 16086194
TI  - [Sports medicine in Germany].
AB  - Sports medicine covers many different aspects, ranging from clinical specialties,
      such as internal medicine, orthopedics or pediatrics to physiology and sports
      sciences. The requirements for sports medicine evolve mainly from exercise
      physiology (elite, leisure and health oriented physical activity), orthopedics
      and traumatology as well as from preventive and rehabilitative issues. In the new
      German curriculum, sports medicine is defined as a subspecialty. Historically,
      sports medicine in Germany has a federal structure with a governing body
      (Deutsche Gesellschaft fur Sportmedizin und Pravention). Due to these facts,
      University Departments of Sports Medicine (which vary greatly in size and
      performance) are either attached to Medical or non-Medical Faculties, such as
      Sports Sciences. In medical schools, sports medicine can be selected as an
      elective subject. However, the main part of teaching sports medicine is covered
      by Sports Science Faculties. In an international context, the strength of German
      sports medicine is its clinical orientation and close cooperation with the sport
      itself, especially high-performance sports. In the future, like in the Anglo-
      American countries, sports medicine in Germany will play a major role in health
      prevention and rehabilitation.

PMID- 16086195
TI  - [Fitness of children--children's health].
AB  - Results of health studies on children and adolescents show clearly their physical
      and psychosocial impairments. Stress, social isolation, familial strains, false
      diet behaviour and above all a lack of activity play a major role as risk factors
      for the health of children. Closely connected to the last-named risk factor, lack
      of activity, is the physical performance or fitness of children and adolescents.
      The findings on physical performance of children and adolescents are still
      heterogeneous. This situation is primarily due to the difficulties in comparing
      the data because of the application of different test procedures as well as the
      different determinations of critical values for "noticeable problems" - thus a
      clear agreement about what test achievements are good or not good is hardly
      possible. Despite these methodological difficulties one can note that literature
      reviews from Bos, Dordel and Gaschler as well as different studies support the
      assumption that the physical performance of children and adolescents has
      decreased in the last two decades. From 1975 until 2000 the difference in ability
      amounts to about 10%, whereas the regression in ability can be seen the plainest
      in course endurance and flexibility, for both boys and girls. In fact physical
      performance and physical fitness are basic health resources. Through the
      fortification of the cardiovascular system, stabilisation of the retaining and
      motion apparatus and the economization of motion executions, physical fitness is
      an important protection against metabolic risks, psychosomatic disorders and
      diseases as well as accidents.

PMID- 16086196
TI  - [Youth sport--youth health. An overview of the current state of research].
AB  - This article presents the current state of research about both the physical
      activity of young people in Germany and its potential effects on health and
      health behaviour. The extent to which adolescents are physically active in their
      leisure time and in sports clubs has been on an unchangingly high level for
      approximately 25 years. More than 80% of them are physically active at least once
      a week and almost every second adolescent is a member in a sports club. The
      findings available do not corroborate the popular belief that the lack of
      physical activity is increasing. All in all, the state of national and
      international research about the interrelationship between sport and health in
      youth age is highly insufficient and inconsistent. Cross-sectional studies show -
      with overall weak correlations -- that physically active young people stand out
      from non-active young people in most parameters, e.g. physical and psychosocial
      health resources, risk factors, complaints, subjective health status, tobacco
      consumption. The comparisons of health relevant behaviour, e.g. accidents, eating
      disorders and alcohol consumption, work to the disadvantage of physically active
      people. So far, the few existing longitudinal studies do not verify systematic
      effects on physical and psychosocial health resources, subjective health and
      health behaviour. However, some international studies show slight effects on the
      risk-factor profile; these effects may well last up to adult age. While the
      comparison of physically active and non-active subjects shows only weak
      correlations, somewhat distinct effects are displayed if physical activity is
      defined in a more differentiated way (frequency, duration, competition
      orientation, kinds of sport).

PMID- 16086197
TI  - [Running as the people's exercise. A brief statement].
AB  - Exercises, especially running, are the most effective measures to protect against
      the wellknown diseases caused by today's lifestyle. The following brief statement
      will focus on the benefits of running.

PMID- 16086198
TI  - [Crossing borders. The motivation of extreme sportsmen].
AB  - In his article "Crossing borders -- the motivation of extreme sportsmen" the
      author gets systematically to the bottom of the question of why extreme sportsmen
      voluntarily take risks and endanger themselves. Within the scope of a
      representative sampling 217 extreme sportsmen -- from the fields of mountain
      biking, trekking and free climbing, canoyning, river rafting and deep sea diving,
      paragliding, parachuting, bungee jumping and survival training -- give
      information about their personal motives. What fascinates them? The attraction of
      risk? The search for sensation? Or the drop out of everyday life? And what comes
      afterwards? Does in the end the whole life become an extreme sport? Fact is: they
      live extremely, because they want to move beyond well-trodden paths. To escape
      the boredom of everyday life they are searching for the kick, the thrill, the no
      limit experience. It's about calculated risk between altitude flight and deep sea
      adventure.

PMID- 16086199
TI  - [Nurturing fair play in competitive sports. Results from a study on competitively
      oriented youth soccer].
AB  - Apologists of sports praise them as an ideal way to prevent addiction and
      violence. Sports critics see it rather as a socialization authority on the morals
      of the fair foul. This contradiction was investigated based on an examination of
      fairness behaviour and fairness education in youth soccer as well as the question
      of the connection between sports and violence and the preventive possibilities of
      sports. Our results point to differences in understanding fairness according to
      age, sex and primarily performance/success orientation. Teenagers learn al ready
      at the latest in the C youth that it is important and right in the interest of
      success to break rules. Thus it applies that the more distinctive the success
      orientation, the more in formal and formal fair play degenerate into fictitious
      action morals of competitive sport and make way for morals of the "fair foul".
      The coaches play an important, even quite obviously the central role as
      socialization agents. In stead of learning fairness, the opposite is often
      conveyed to many young people in the organizations. However, our examinations
      also show that coach es can positively influence both fairness understanding and
      fairness behaviour of young footballers. Coach es are thus challenged as role
      models to exemplify fair play by their own actions.

PMID- 16086200
TI  - [Benefits of sport activity in adulthood. A longitudinal study over 10 years].
AB  - This article deals with the question of which longitudinal effect physical
      activity at the adult age can have on physical fitness and on people's subjective
      as well as objective state of health. Are persons who are regularly and
      continuously physically active healthier and fitter than people beginning
      physical activity at a later age, or than those who have never been physically
      active at all? The results of the presented longitudinal study, run over a time
      range of 10 years, with subjects at the middle and later adult age, show that on
      average physical fitness and subjective health decline with in the analysed time
      range, but positive effects of physical activity do exist. These show up in a
      decelerated decline. The constant sportsmen benefit most here, but also a late
      start with physical activity can improve and stabilize physical fitness and
      health. Anyway, former physical activity is no guarantee for lifelong fitness and
      health. The group of the dropouts registers large degradations in both variables
      after quitting physical activity.

PMID- 16086201
TI  - [Physical activity, sport and successful aging].
AB  - The reasons for the increasing significance of physical activity and sports in
      the aging process and in higher ages are related to the socio-economic
      background. The biocultural context of the socio-demographic development, the
      understanding of sport for the elderly and successful aging is dealt with
      comprehensively. The main focus of the contribution is on the relationship
      between physical activity and life expectancy, physical fitness level, and
      cognitive and psychical health.

PMID- 16086202
TI  - [Effects of exercise in chronically ill patients. Examples from oncology and
      neurology].
AB  - Epidemiologic studies increasingly have demonstrated a correlation between
      physical inactivity and certain chronic diseases. Already in the 1970s exercise
      programs for cardiovascular patients were established, whereas in other severe
      chronic illnesses such as breast cancer or multiple sclerosis exposure to
      physical stress seemed to be a contraindication. Today there is a grow ing body
      of evidence demonstrating positive physical as well as psychic effects of
      exercise training in patients with these diseases. These studies are summarized
      and complementary studies of our group are described in more detail. In patients
      with breast cancer we were able to demonstrate persistent psychosocial effects
      even 1 year after completion of the training program. In patients with multiple
      sclerosis we could confirm an induction of neurotrophic factors in trained
      individuals. Correspondingly, there is accumulating evidence showing positive
      effects of exercise on cognitive function, especially in the aged. Potential
      pathophysiological pathways regarding a progression to dementia are presented.
      Consequently exercise programs could play a pivotal role in the prevention and
      therapy of the cognitive decline in the aged in an aging society.

PMID- 16086203
TI  - [Physical training in the treatment of psychological disorders].
AB  - Numerous studies in healthy volunteers have demonstrated positive psychological
      effects of regular aerobic exercise, such as reduction of anxiety or depressive
      symptoms, in crease of self-esteem and improved stress management. There is also
      solid evidence that regular exercise is associated with therapeutic effects in
      psychiatric patients suffering from depressive and possibly other psychiatric
      disorders. The present article reviews the relevant literature and summarizes
      neurobiological effects of exercise, which might play a role in the effectiveness
      of therapeutic exercise. For instance, there is experimental evidence that
      regular exercise induces a downregulation of certain central serotonergic
      receptors, which play an important role in the pathogenesis of anxiety and
      depression. The last part of the article focuses on the practical aspects of how
      exercise programs can be utilized in the treatment of psychiatric disorders.

PMID- 16086204
TI  - [Cardiovascular risks in sports].
AB  - Cardiovascular diseases are responsible for about 50% of total mortality in
      Germany. Regular physical activity is associated with a reduction in
      cardiovascular morbidity and mortality in the long term, both in primary and
      secondary prevention. Prospective epidemiological studies have shown that both
      moderate and intensive physical activity have a positive effect on cardiovascular
      risk. Even physical activity begun during middle age or later leads to a
      reduction in cardiovascular risk. However, during and immediately after an acute
      episode of physical activity, there is an increased risk of acute coronary
      events. Particularly untrained persons with an existing coronary heart disease
      are at risk for an event. Even in physically fit persons, the risk is increased
      during and after acute physical activity. Regular physical activity, however, is
      an important protective factor and reduces the risk of coronary events during
      acute strenuous exercise. Despite the increased risk during acute episodes of
      physical activity, regular physical activity is an important ingredient in the
      prevention of cardiovascular and other diseases. Current guidelines, therefore,
      recommend regular physical activity.

PMID- 16086205
TI  - [Sports injuries and overuse syndromes].
AB  - The benefit of regularly performed physical activity as a fundamental component
      of a healthy lifestyle is uncontradicted. The number of persons who participate
      in sports in Germany is approximately more than 40 million people, whereof 27.5
      million are organised in sport associations. Every year 1.5-2 million sports
      injuries occur in Germany, which represent 25-30% of all accidents. The costs for
      treatment amount to a total of 1.5 billion euros. It is estimated that 80% of all
      sports injuries could be prevented if training and competition were performed
      correctly. The patterns and risk of injuries differ between particular sport
      disciplines and are therefore difficult to estimate. Knowledge of specific injury
      risks is indispensable for prevention of sports injuries. Furthermore this
      knowledge facilitates both sports physicians' diagnosis and therapy and guidance
      of the patient. In this review epidemiological data of sport traumatology are
      surveyed, patterns of injuries of particular sports are described in detail and
      prevention strategies are given. In a separate section specifics of sports
      injuries in children are discussed.

PMID- 16086206
TI  - [Efficient killing of anthrax spores using aqueous and alcoholic peracetic acid
      solutions].
AB  - We analysed the sporicidal effect of different concentrations of aqueous and
      alcoholic peracetic acid (PAA) solutions on anthrax spores in suspension and germ
      carrier tests. In activation of anthrax spores in suspension assays was achieved
      in less than 2 min using 1% PAA solution and in less than 3 min using 0.5% PAA
      solution, respectively. In contrast, in germ carrier as says, a test under
      practical conditions, spores on 38% of the germ carriers survived treatment with
      1% PAA solution for 15 min. The use of PAA in 80% ethyl alcohol outclassed the
      sporicidal effect of aqueous PAA solutions in both suspension and germ carrier
      assays. Anthrax spores on 14% of germ carriers tested survived 30 min of
      treatment with a 1% aqueous PAA solution. In contrast anthrax spores were
      reliably inactivated under the same test procedure using a 1% alcoholic PAA
      solution for 30 min. The proven enhancement of the sporicidal effect of alcoholic
      PAA solutions should be kept in mind when using disinfectants in practice. In
      further surveys we will optimise the test conditions.

PMID- 16086210
TI  - Long-term survival of patients with gallbladder cancer detected during or after
      laparoscopic cholecystectomy.
AB  - Little evidence is available regarding long-term survival of patients with
      gallbladder cancer that is discovered at the time of laparoscopic cholecystectomy
      (LC). Therefore the present study was performed to evaluate long-term outcomes of
      this disease. Of 1546 patients who underwent LC for benign gallbladder disease
      between January 1992 and January 2002, 8 patients (0.5%) had cancers that were
      found during or after LC. The median follow-up period was 55 months (range: 36
      142 months). The gallbladder was resected without perforation in all cases.
      During surgery there was a suspicion of malignancy in 6 of 8 cases. Frozen
      section analysis showed that 2 had TNM stage Tis tumors, 2 had T1a tumors, and 2
      had T2 tumors. Two patients with T2 tumors were immediately converted to extended
      cholecystectomy. The final pathology revealed another 2 tumors, and demonstrated
      that 3 patients had Tis tumors, 3 had T1a tumors, and 2 had T2N0M0 tumors. None
      of the patients underwent additional surgery. All patients survived with no
      evidence of recurrence during the median follow-up of 55 months. In conclusion,
      before and during LC, we have not overlooked T2 or more advanced tumor, which
      requires additional procedures for curative resection. This might result in good
      survival. We consider that an intensive preoperative work-up and meticulous
      inspection of the opened gallbladder should be mandatory to detect gallbladder
      cancer in patients who undergo LC. At present, this is not routinely practiced.

PMID- 16086211
TI  - Ex vivo sentinel lymph node study for rectal adenocarcinoma: preliminary study.
AB  - Intraoperative sentinel lymph node (SLN) detection has been reported for colon
      cancer, but no study has focused on rectal cancer. Only an ex vivo technique can
      be performed easily in this location. We evaluated SLN detection using blue dye
      injection in patients with rectal adenocarcinoma. This prospective study included
      31 patients. Preoperative radiotherapy (45 Gy) was done in 15 cases. After
      proctectomy the surgical specimen was examined in the operating room. Submucosal
      peritumoral injections were done. One to three SLNs were retrieved. The SLNs were
      sectioned at three levels and examined histologically and then, if negative by
      hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC). There were 7
      abdominoperineal resections, 12 colorectal anastomoses, 11 coloanal anastomoses,
      and 1 Hartmann procedure. The median number of lymph nodes harvested was 21 (7
      38). A SLN was identified in 30 cases (feasibility 97%). The mean number of SLNs
      was 2 (0-3). A micrometastasis was discovered in 3 of 23 pNO cases when H&E was
      used on multisection levels, thus changing the stage to pN1. Each time the only
      positive lymph node was the SLN. IHC evaluation did not change the result, as
      only isolated tumor cells were discovered in one case. Only four of seven N+
      patients had a positive SLN, resulting in a false-negative rate of 43%. Ex vivo
      detection of SLNs is possible for rectal cancer and is a simple technique.
      Classic analysis using H&E remains the gold standard. However, SLNs detection can
      change the tumor stage by upstaging nearly 15% of the tumors from T2-3N0 to T2-3
      N+.

PMID- 16086212
TI  - Abdominal angina in patients with a midgut carcinoid, a sign of severe pathology.
AB  - In 36 consecutive patients with a foregut carcinoid with extensive local tumor
      growth and liver metastases with a carcinoid syndrome, six patients had
      complaints of postprandial abdominal pain and attacks of subileus based on
      segmental intestinal ischemia. A diagnosis of abdominal angina was supported by a
      positive response to nitroglycerin in two and ischemia of the ileum demonstrated
      by angiography in two other patients. Complaints were reduced in all patients
      after surgery. Histopathology of the resected small bowel specimens showed
      elastic vascular sclerosis in three patients and ischemic changes in three other
      patients, confirming the clinical diagnosis. Resection of ischemic bowel can
      provide relief in patients with segmental intestinal ischemia caused by carcinoid
      induced vascular sclerosis.

PMID- 16086213
TI  - When is curative gastrectomy justified for gastric cancer with positive
      peritoneal lavage cytology but negative macroscopic peritoneal implant?
AB  - For gastric cancer patients who have no peritoneal seeding at a macroscopic level
      but positive results in the peritoneal lavage cytology (PLC), the prognostic
      benefit expected by surgical resection is still controversial. During the period
      1975-1994 as series of 417 consecutive patients without distant organ metastases
      underwent surgical resection for gastric cancer that had invaded the subserosal
      or deeper layers of the stomach wall. Immediately after laparotomy, the pouch of
      Douglas was washed with 100 ml of physiologic saline solution, and the fluid was
      collected for cytologic examination (four slide glasses) using Giemsa and
      Papanicolaou staining methods. According to the macroscopic (P) and cytologic
      (Cyt) results, the 417 patients were classified into three groups: P(+) (n = 97);
      P(-)/Cyt(+) (n = 25); and P(-)/Cyt(-) (n = 295). Their 3-year survival rates
      after surgical resection were 4%, 24%, and 48%, respectively (p = 0.0001: P(
      )/Cyt(+) vs. P(-)/Cyt(-); p = 0.0018: P(-)/Cyt(+) vs. P(+). Among the 25 P(
      )/Cyt(+) patients, postoperative survival was not associated with the T stage, N
      stage, cellular atypism, or cluster formation but with the number of cancer cells
      per slide during PLC. The 3-year survival rate was 35% for the subgroup with
      fewer than 10 cancer cells per slide (17 patients) and 0% for the other subgroup
      with 10 or more cancer cells per slide (8 patients) (p = 0.017). For P(-)/Cyt(+)
      patients, who represent a subgroup of gastric cancer patients with an
      intermediate survival rate between the P(-)/Cyt(-) and P(+) patients, the number
      of cancer cells observed during PLC offers a potent prognostic indicator for the
      gastrectomy.

PMID- 16086214
TI  - Prevalence of prothrombotic abnormalities in patients with acute mesenteric
      ischemia.
AB  - Acute mesenteric ischemia (AMI) is a rare condition that may be associated with a
      variety of congenital prothrombotic disorders (PDs). The purpose of this study
      was to assess the prevalence of these disorders in 28 AMI patients compared with
      103 healthy individuals from the northeastern region of Turkey. They were
      screened for protein C, antithrombin III, and protein S deficiencies; and gene
      analysis was performed using the polymerase chain reaction. A PD was revealed in
      16 (57%) patients and 33 (32%) controls (p = 0.020). Factor V Leiden (FVL),
      prothrombin G20210A mutation, and TT677 homozygous mutation of
      methylenetetrahydrofolate reductase was detected in 10 (36%) patients versus 16
      (15%) controls (p = 0.035), 3 (11%) patients versus 10 (9%) controls (p = 1.00),
      and 1 (3%) patient versus no controls, respectively. Consistent with caucasian
      ethnic groups, there was high prevalence of PDs, especially FVL; and these
      abnormalities might be a significant predisposing factor in the pathogenesis of
      AMI.

PMID- 16086216
TI  - Should we deny surgery for malignant hepato-pancreatico-biliary tumors to elderly
      patients?
AB  - Malignant hepato-pancreatico-biliary (HPB) tumors have their highest incidence
      within the sixth to eighth decades of life. The aging of the world population has
      resulted in a dramatic increase in the number of elderly patients considered for
      resection of malignant HPB tumors. Because elderly patients are more likely to
      have more co-morbidities, cognitive impairment, and decreased life expectancy,
      the benefit and appropriateness of these procedures must be scrutinized for
      geriatric patients. Therefore, many surgeons have compared the perioperative and
      long-term outcome of hepatic and pancreatic resections for elderly and younger
      patients. In most series the elderly population was defined by an age of 70 years
      or older. The results demonstrate that hepatic resection for hepatocellular
      carcinoma and colorectal liver metastases can be safely performed in well
      selected elderly patients with long-term outcome comparable to younger patients.
      Similar findings are also reported for pancreatic resection in elderly patients
      with either ampullary or pancreatic cancer. Although the survival benefit of
      pancreatico-duodenectomy is limited in all age groups, the absence of competitive
      therapy justifies this procedure as the sole curative option in younger as well
      as older patients. Data on resection of gallbladder cancer and hilar bile duct
      cancer in the elderly are sparse, but there is evidence from large series on
      resection of these types of tumors that advanced age per se is not a risk factor
      for reduced outcome. Therefore, surgical options should not be denied to elderly
      patients with a malignant HPB tumor, and the evaluation should include surgeons
      expert in HPB surgery.

PMID- 16086218
TI  - Evaluation of the paradoxical sphincter contraction by a strain/squeeze index in
      constipated patients.
AB  - PURPOSE: One finding in patients with constipation is the paradoxical
      puborectalis contraction, i.e. , activation of the sphincter muscles during
      straining instead of relaxation. The aims of this study were to evaluate the
      importance of needle placement in sphincter-electromyography and to evaluate a
      strain/squeeze index in constipated patients and control subjects. METHODS: We
      investigated consecutively 194 constipated patients and 16 control subjects with
      integrated electromyography during straining and squeezing and calculated a
      strain/squeeze index. The examination was performed in the puborectalis and in
      the external anal sphincter muscle through hook-electrodes. RESULTS: There was a
      strong correlation between indices in the puborectalis muscle and in the external
      anal sphincter muscle (r = 0.70-0.80, P < 0.001). Forty-seven patients (24
      percent) had a mean index of greater than 50 compared with none in the control
      group (P = 0.01). Mean overall index in patients was 24 (range, 0-306) vs. 18
      (range, 0-45) in controls (P = 0.12). Patients with an index greater than 50 had
      impaired rectal evacuation (P < 0.001), increased threshold for urge (P < 0.05),
      and tended to have fewer stools (P = 0.06). CONCLUSION: Quantification of
      paradoxical contraction in the puborectalis and external anal sphincter with a
      strain/squeeze index differentiates patients in whom paradoxical activity may be
      a cause of constipation. An index above 50 may be of pathologic significance.
      Correlations between activity in the puborectalis and external anal sphincter
      muscle were strong which suggests that investigation in one of them is
      sufficient.

PMID- 16086219
TI  - Laparoscopic vs. open colectomies in octogenarians: a case-matched control study.
AB  - PURPOSE: The aim of this study was to define any benefits in terms of early
      outcome for laparoscopic colectomy in patients over 80 years old compared with
      open colectomy. METHODS: Sixty-one patients undergoing laparoscopic colectomy for
      colorectal cancer were matched to 61 open colectomy patients for gender, age,
      year of surgery, site of cancer, and comorbidity on admission. Independence
      status on admission and at discharge from the hospital was also evaluated.
      RESULTS: Mean (standard deviation) age was 82.3 (3.5) years in the laparoscopy
      group and 83.1 (3.3) years in the open group. Conversion rate was 6.1 percent.
      Operative time was 49 minutes longer in the laparoscopy group (P = 0.001). The
      overall mortality rate was 2.4 percent. The morbidity rate was 21.5 percent in
      the laparoscopy group and 31.1 percent in the open group (P = 0.30). Patients in
      the laparoscopy group had a faster recovery of bowel function (P = 0.01) and a
      significant reduction of the mean length of hospital stay (9.8 vs. 12.9 days for
      the open group, P = 0.001). Laparoscopy allowed a better preservation of
      postoperative independence status compared with the that of the open group (P =
      0.02). CONCLUSION: Laparoscopic colectomy for cancer in octogenarians is safe and
      beneficial including preservation of postoperative independence and a reduction
      of length of hospital stay.

PMID- 16086220
TI  - A defunctioning ileostomy does not prevent clinical anastomotic leak after a low
      anterior resection: a prospective, comparative study.
AB  - PURPOSE: Defunctioning ileostomy or colostomy is still routinely performed after
      low anterior resection in the belief that diverting the fecal stream will prevent
      anastomotic dehiscence. However, an ileostomy is not without morbidity for the
      patient. This study aims to determine if a diverting stoma is really necessary
      after a low anastomosis. METHODS: All low or ultralow anterior resections done in
      this department were performed by consultant-grade surgeons in a standardized
      manner. The patients were all monitored closely after surgery for clinical signs
      of an anastomotic leak. There were 1078 patients who underwent elective low or
      ultralow anterior resections in a ten-year period between 1994 and 2004. Twelve
      of them were irradiated before surgery; they were excluded from the study. During
      a seven-month period from February 2004 through August 2004, 324 patients who
      underwent such procedures were not defunctioned. These were compared with 742
      patients who were previously defunctioned with a proximal stoma. The results were
      analyzed using the Pearson chi-squared test. RESULTS: Thirteen (4 percent)
      patients who were not defunctioned developed a clinical anastomotic leak, whereas
      the leak rate for those who were defunctioned was 3.8 percent. There was no
      statistical difference demonstrated. Ninety-five percent of patients who
      developed a leak required surgical intervention; the remaining 5 percent could be
      dealt with by radiologic drainage. The overall mortality rate for anastomotic
      leak in this department is 7.3 percent. CONCLUSION: A diverting stoma does not
      reduce postoperative anastomotic leak rate. Rather, it reduces the otherwise
      catastrophic effects of an anastomotic leak such as fecal peritonitis and
      septicemia. An ileostomy carries certain morbidity and also adds to the cost of
      the entire operation. Therefore, it should not be performed routinely. Instead,
      it should be performed selectively in patients with poorly prepared bowels,
      coupled with a distal limb washout, and in patients with significant
      comorbidities who can ill afford the complications of a leak.

PMID- 16086221
TI  - Limitations of barium enema performed as an adjunct to incomplete colonoscopy.
AB  - PURPOSE: Colonoscopy is believed to be inadequate in 4 to 24 percent of
      procedures. Barium enema often is utilized to complete the examination. In
      radiology literature, a successful barium enema in this setting requires only
      that the cecum has been reached. In this study, completion barium enema was
      assessed for both completeness and quality of proximal visualization. METHODS:
      The charts of 16,216 patients undergoing colonoscopy at Saint Vincent Health
      Center from July 1995 to July 2003 were reviewed to identify patients who
      underwent barium enema within six months of an incomplete colonoscopy. Incomplete
      colonoscopies were audited for history of previous abdominal/pelvic surgery,
      level of colon attained, and apparent reasons for failure. Corresponding barium
      enema reports were evaluated in a similar fashion. RESULTS: In 485 patients (2.9
      percent), colonoscopy was incomplete. One hundred eighteen patients underwent
      barium enema after incomplete colonoscopy. In these patients, sharp angulation
      (42 percent) or redundancy/looping (31 percent) most often limited endoscopy.
      Among the barium enema studies, 91 (77 percent) were technically adequate. Twenty
      seven studies were suboptimal (poor preparation/intolerance = 7, redundancy = 6,
      poor filling = 6, stricture/narrowing = 6, severe diverticulosis = 2). Two
      patients demonstrated additional polyps. There was no correlation between reasons
      for endoscopic failure and inadequacy of barium enema. Completeness of barium
      enema was not affected by previous pelvic surgery. Immediate barium enema was no
      less complete than a delayed study. CONCLUSIONS: The reliability of barium enema
      after incomplete colonoscopy is less than previously reported.

PMID- 16086222
TI  - Medical vs. surgical management of thrombosed external hemorrhoids.

PMID- 16086223
TI  - Technique and long-term results of intersphincteric resection for low rectal
      cancer.
AB  - PURPOSE: Intersphincteric resection of low rectal tumors is a surgical technique
      extending rectal resection into the intersphincteric space. This procedure is
      performed by a synchronous abdominoperineal approach with mesorectal excision and
      excision of the entire or part of the internal sphincter. This study was designed
      to evaluate the long-term results of this method focused on continence function
      and oncologic results. METHODS: From 1984 to 2000, a total of 121 patients were
      operated on. The patients were evaluated prospectively according to a detailed
      preoperative and postoperative program. RESULTS: One hundred seventeen patients
      had rectal cancers, two had dysplastic villous adenomas, and two had carcinoid
      tumors. Cancers were staged according to the Dukes classification (Stage A in 41
      percent, Stage B in 28 percent, and Stage C in 31 percent; median distance from
      the anal margin, 3 (range, 1-5) cm). Postoperative complications were: one death
      because of pulmonary embolism, 5.1 percent developed an anastomotic fistula, one
      patient had a fistula to the bladder requiring reoperation, one patient with
      ileus needed relaparotomy as well as one for intra-abdominal hemorrhage and a
      small-bowel fistula. One patient developed a fistula after closing the protective
      colostomy. Five patients developed late strictures of the coloanal anastomosis.
      After a median follow-up of 72.86 months, 5.3 percent of patients developed local
      recurrence. The continence status was satisfactory with 16 patients (13.7
      percent) showing continence for solid stool only, and 1 patient (0.8 percent)
      showing episodes of incontinence. A transient problem was a high stool frequency
      after closure of the protective stoma. CONCLUSIONS: Intersphincteric resection is
      a valuable procedure for sphincter-saving rectal surgery. We showed that this
      technique has satisfactory long-term results in functional and oncologic
      respects. An important prerequisite is a careful preoperative evaluation of local
      tumor spread with rectal magnetic resonance imaging excluding infiltration of the
      external sphincter.

PMID- 16086224
TI  - Gastrointestinal involvement of posttransplant lymphoproliferative disorder in
      lung transplant recipients: report of a case.
AB  - PURPOSE: Lymphoproliferative disorder is a well-recognized complication of lung
      transplantation. Risk factors include Epstein-Barr virus infection and
      immunosuppression. The gastrointestinal manifestations of post-transplant
      lymphoproliferative disorder in lung transplant recipients have not been fully
      characterized. METHODS: Case presentation and 16 previously reported cases of
      post-transplant lymphoproliferative disorder with gastrointestinal involvement
      are reviewed. RESULTS: Patient ages ranged from 25 to 65 (median, 52) years.
      Median time from lung transplantation to onset of posttransplant
      lymphoproliferative disorder was 36 (range, 1-109) months; 35 percent of cases
      (6/17) occurred within 18 months; Eighty-eight percent of patients (15/17) had
      positive Epstein-Barr virus serology before transplantation. In five patients (29
      percent), the posttransplant lymphoproliferative disorder also involved sites
      other than the gastrointestinal tract. The most common gastrointestinal site of
      posttransplant lymphoproliferative disorder was the colon, followed by the small
      intestine and stomach. Clinical features included abdominal pain, nausea, and
      bloody diarrhea. Diagnosis was based on typical pathologic changes on
      gastrointestinal tract biopsy obtained mainly by colonoscopy. Treatment included
      a reduction in the immunosuppressive regimen in 15 of 17 cases (88 percent) and
      surgical resection in 10 (59 percent). One patient was untreated. Seven of 16
      patients (44 percent) responded to treatment and 9 patients died. Median time
      from onset of posttransplant lymphoproliferative disorder to death was 70 (range,
      10-85) days. CONCLUSIONS: Posttransplant lymphoproliferative disorder with
      gastrointestinal involvement is a unique entity that should be considered in all
      Epstein-Barr-Virus-positive lung transplant recipients who present with abdominal
      symptoms. Although immunosuppressive modulation and resection can lead to
      remission, the risk of death is 50 percent.

PMID- 16086225
TI  - VeloceGenomics: an accelerated in vivo drug discovery approach to rapidly predict
      the biologic, drug-like activity of compounds, proteins, or genes.
AB  - PURPOSE: The aim of this study is to test the predictive power of in vivo
      multiorgan RNA expression profiling in identifying the biologic activity of
      molecules. METHODS: Animals were treated with compound A or B. At the end of the
      treatment period, in vivo multiorgan microarray-based gene expression data were
      collected. Investigators masked to the identity of the compounds analyzed the
      transcriptome signatures to define the molecular pathways affected by treatment
      and to hypothesize the biologic activity and potential therapeutic indications of
      the blinded compounds. RESULTS: For compound A, G-protein-coupled receptors and
      factors associated with cell growth were affected-growth hormone/insulin-like
      growth factor-1, glucagon/insulin axes, and general somatomedin-like activity.
      Deblinding showed the compound to be a somatostatin analog, SOM230, confirming
      the accuracy of the predicted biologic activity. For compound B, components of
      the inflammatory cascade potentially mediated by lipopolysaccharide, tumor
      necrosis factor, or proinflammatory cytokines were affected. The gene expression
      signatures were most consistent with an interleukin-6 family activity. Deblinding
      revealed that compound B was leukemia inhibitory factor. CONCLUSIONS:
      VeloceGenomics is a strategy of coupling in vivo compound testing with genomic
      technologies. The process enables prediction of the mechanism of action and,
      coupled with other relevant data, prediction of the suitability of compounds for
      advancement in the drug development process.

PMID- 16086226
TI  - Alteration of the pharmacokinetics of COL-3, a matrix metalloproteinase
      inhibitor, due to acute gastrointestinal toxicity of doxorubicin.
AB  - PURPOSE: Combination of COL-3, a matrix metalloproteinase inhibitor, and
      doxorubicin (DOX) might be a promising anticancer regimen. The present study was
      to examine the potential pharmacokinetic interactions and toxicity profile
      following their coadministration in rats. METHODS: Normal rats were treated with
      single agent or different combinations with oral or intravenous COL-3 and DOX,
      and the bile-duct cannulated (BDC) rats received oral COL-3 plus DOX. In a
      separate disposition study, the effects of DOX on the biliary, urinary, and fecal
      excretion of COL-3 were examined. In addition, the effects of DOX on in vitro
      protein binding, metabolism, and transport of COL-3 across Caco-2 monolayers were
      investigated. RESULTS: COL-3 did not affect the pharmacokinetics of DOX in rats.
      However, treatment with DOX significantly decreased the oral absorption, and
      prolonged the elimination, of COL-3 in the normal rats, but not in the BDC rats.
      DOX did not alter the biliary and urinary excretion of COL-3, but significantly
      decreased the fecal excretion of COL-3. DOX significantly enhanced the
      basolateral to apical flux of COL-3 across Caco-2 monolayers, but had no apparent
      effects on the protein binding and metabolism of COL-3. The combination of DOX
      with oral COL-3 did not significantly (p > 0.05) increase the acute diarrhea
      score and intestinal damage compared to rats receiving DOX alone. CONCLUSIONS:
      These results indicated that DOX altered the oral absorption and elimination of
      COL-3, largely resulting from gastrointestinal toxicity caused by biliary
      excretion of DOX. Further studies are required to explore the efficacy and
      optimized dosage regimen of this promising combination.

PMID- 16086227
TI  - Cost-effectiveness of positron emission tomography in breast cancer.
AB  - PURPOSE: In this study, we used quantitative decision tree modeling to assess the
      cost-effectiveness of a positron emission tomography (PET)-based management
      scenario for breast cancer in Canada. PROCEDURES: Two patient management
      scenarios were compared (with and without PET). A metaanalysis of studies for the
      accuracy of PET in staging breast cancer was conducted. Life expectancies were
      calculated. Management costs were determined from previous cost-effective
      analyses, management costs from our institutions, and recently published Canadian
      cost estimates of various procedures. RESULTS: A cost savings of $695 per person
      is expected for the PET strategy, with an increase in life expectancy (7.4 days),
      when compared with the non-PET strategy. This cost savings remained in favor of
      the PET strategy when subjected to a sensitivity analysis. CONCLUSIONS: The use
      of a PET management strategy for the staging of breast cancer is expected to
      remain economically viable in Canada under various economic conditions.

PMID- 16086228
TI  - Welcomed triplets following gestation with retained intrauterine device.
AB  - Multiple gestations with concurrent intrauterine devices (IUDs) are rare events.
      We handled the case of a woman who discovered she was pregnant with triplets
      after the 12th week of gestation. Upon the mother's request the IUD was removed
      immediately and the pregnancy led a normal course until the planned caeserean
      delivery of three baby girls. This is the first report of triplet births after an
      early sharing occupancy of the narrow uterine cavity with an IUD. Such a
      gestation upon discovery should not automatically be presumed undesirable.
      Especially when faith issues are predominant such cases may end with satisfied
      parents as demonstrated in this case.

PMID- 16086229
TI  - Jewish gynecologists in Germany in the first half of the twentieth century.
AB  - The political changes in Germany of 1933 led to discrimination, expulsion and
      emigration of Jewish doctors. This article addresses the memory of gynecologists
      who were eminent physicians or made fundamental discoveries. Short biographies of
      Ludwig Fraenkel, Selmar Aschheim, Bernhard Zondek, Ludwig Adler, Robert Meyer and
      Paul Ferdinand Strassmann highlight their work and their links to the
      Gynecological Society in Berlin and to the German Society of Gynecology, the
      foundation of the latter being inspired by Wilhelm Alexander Freund from
      Strasbourg.

PMID- 16086230
TI  - Role of the beta1-integrin subunit in the adhesion, extravasation and migration
      of T24 human bladder carcinoma cells.
AB  - The abilities of tumor cells to extravasate from the blood vessel system and to
      migrate through the connective tissue are prerequisites in metastasis formation.
      Both processes are chiefly mediated by integrins, which mediate both cell-cell
      and cell-matrix interactions. We investigated the role of integrin subunits in
      the adhesion, extravasation and migration of the highly invasive human bladder
      carcinoma cell line T24. Here we show that inhibition of the beta(1)-integrin
      subunit using the specific beta(1)-integrin blocking antibody 4B4 significantly
      reduces the adhesion to HUVEC and transmigratory activity of T24 cells. The
      blockade of the beta(1)-integrin subunit also resulted in a significantly reduced
      locomotory activity of T24 cells. A detailed cell migration analysis on a single
      cell level revealed that blockade of the beta(1)-integrin subunit leads to an
      altered migration pattern of single cells but does not influence migration per
      se. Migration parameters such as time active, velocity and distance migrated were
      significantly reduced as compared to untreated control cells. Our observations
      strongly suggest a central role for the beta(1)-integrin subunit in forming the
      cell-cell and cell-matrix bonds necessary for adhesion, extravasation and
      migration.

PMID- 16086231
TI  - The identification of chromosome abnormalities associated with the invasive
      phenotype of uveal melanoma in vitro.
AB  - Tumour cell cultures are often highly heterogeneous, containing sub-populations
      of cells with differing characteristics. To identify chromosome abnormalities
      that are associated with the invasive phenotype, we isolated highly invasive
      uveal melanoma cell populations using the Transwell assay. Using this invasion
      assay, invasive sub-populations of primary uveal melanoma short-term cultures,
      and an established cell line, were specifically isolated. A series of sequential
      assays were undertaken to enrich the invasive population, and the enhanced
      invasive ability was confirmed by Transwell invasion assay. Chromosome
      abnormalities in invasive and parental cells were identified by karyotyping and
      confirmed by comparative genome hybridisation. Invasive sub-populations of uveal
      melanoma cells were isolated from 3 uveal melanoma short term cultures and a
      uveal melanoma cell line. In all cases, invasive sub-populations had either
      acquired additional chromosome abnormalities to those present in the parental
      cell line, or other abnormalities present in the parental lines were lost. In the
      established cell line (SOM 157), invasive cells were characterised by widespread
      chromosomal instability, frequent telomere associations and additional copies of
      chromosome 20. The invasive phenotype of SOM 196 associated with the presence of
      a derivative chromosome 5, der(5)t(5;11)(q35;q12) whilst a translocation
      t(17;20)(q12;q13) was predominant amongst non-invasive cells. In two additional
      cultures, deletions on chromosome 6q were associated with reduced invasive
      ability. In conclusion, highly invasive populations of uveal melanoma cells
      demonstrate chromosomal abnormalities that differ from non-invasive cells. These
      include chromosome instability and abnormalities of chromosome 20, observations
      echoing those seen in metastatic uveal melanoma.

PMID- 16086232
TI  - Upregulated MT1-MMP/TIMP-2 axis in the TSU-Pr1-B1/B2 model of metastatic
      progression in transitional cell carcinoma of the bladder.
AB  - Muscle invasive transitional cell carcinoma (TCC) of the bladder is associated
      with a high frequency of metastasis, resulting in poor prognosis for patients
      presenting with this disease. Models that capture and demonstrate step-wise
      enhancement of elements of the human metastatic cascade on a similar genetic
      background are useful research tools. We have utilized the transitional cell
      carcinoma cell line TSU-Pr1 to develop an in vivo experimental model of bladder
      TCC metastasis. TSU-Pr1 cells were inoculated into the left cardiac ventricle of
      SCID mice and the development of bone metastases was monitored using high
      resolution X-ray. Tumor tissue from a single bone lesion was excised and cultured
      in vitro to generate the TSU-Pr1-B1 subline. This cycle was repeated with the TSU
      Pr1-B1 cells to generate the successive subline TSU-Pr1-B2. DNA profiling and
      karyotype analysis confirmed the genetic relationship of these three cell lines.
      In vitro, the growth rate of these cell lines was not significantly different.
      However, following intracardiac inoculation TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2
      exhibited increasing metastatic potential with a concomitant decrease in time to
      the onset of radiologically detectable metastatic bone lesions. Significant
      elevations in the levels of mRNA expression of the matrix metalloproteases (MMPs)
      membrane type 1-MMP (MT1-MMP), MT2-MMP and MMP-9, and their inhibitor, tissue
      inhibitor of metalloprotease-2 (TIMP-2), across the progressively metastatic cell
      lines, were detected by quantitative PCR. Given the role of MT1-MMP and TIMP-2 in
      MMP-2 activation, and the upregulation of MMP-9, these data suggest an important
      role for matrix remodeling, particularly basement membrane, in this progression.
      The TSU-Pr1-B1/B2 model holds promise for further identification of important
      molecules.

PMID- 16086233
TI  - The transition to the metastatic phenotype of rat lymphoma cells involves up
      regulation of IL-10 receptor expression and IL-10 secretion.
AB  - Interleukin 10 (IL-10) is a Th2 anti-inflammatory cytokine that participates in
      the regulation of the immune response at several levels. Its production has been
      implicated in the immunosuppression frequently observed in tumor bearing hosts.
      The broad spectrum of IL-10 biologic activities is mediated by its binding to its
      cognate receptor (IL-10R). We have already demonstrated the overproduction of IL
      10 by B-cell lymphoma tumor bearing rats and, also, that IL-10 could act as a
      growth factor for metastatic cells. Considering the importance to unravel each
      feature of the complex biology of metastasis, the goal of the present study was
      to investigate the expression of IL-10 receptor (IL-10R), at mRNA and protein
      level, in primary tumor and metastatic cells from a rat B-cell lymphoma, along
      with the production of IL-10 by both tumor cell types. Our results indicate that
      IL-10, besides its immunoregulatory effect, would act as an autocrine growth
      factor for cells with metastatic phenotype. Also, the up-regulation of IL-10 and
      IL-10R expression would be part of the transition from primary tumor to the
      metastatic phenotype.

PMID- 16086234
TI  - Establishment and characterization of three novel human gastric cancer cell lines
      with differentiated intestinal phenotype derived from liver metastasis.
AB  - Gastric cancers with liver metastasis are fatal diseases with rapid progression
      and poor patient outcome. To date, however, the molecular basis of their growth
      and metastasis remains essentially unknown, largely because of the presence of
      few available gastric cancer cell lines established from liver metastasis. In the
      present study, we developed two novel cultured cell lines (designated GLM-1 and
      GLM-2) and one transplantable line in nude mice (designated GLM-3) derived from
      liver metastasis of gastric cancer patients. These GLM cell lines share unique
      biological features such as differentiation, growth and metastasis. They form
      moderately differentiated tumors with CD10 positive and MUC2 negative intestinal
      absorptive phenotype when injected into nude mice. Their growth is stimulated by
      EGF and TGF-alpha in vitro like other gastric cancer cell lines. However, GLM
      cells differ from conventional gastric cancer cell lines in their high apoptotic
      rate, even in the absence of apoptosis inducing stimuli as revealed by Caspase3/7
      assay and the TUNEL method. This apoptosis is further enhanced by
      phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), but not by MEK1/2
      inhibitor (U0126), indicating the strong dependency of their survival on PI3K/Akt
      pathway rather than MAPK pathway, the major downstream signaling pathways of
      EGFR. GLM-1 cells can metastasize to the liver after intrasplenic injection, and
      GLM-3 cells have spontaneous lung metastatic potential after subcutaneous
      transplantation, respectively. These results indicate that the GLM series are the
      first cell lines reflecting the intestinal-type differentiated adenocarcinoma, a
      major subtype of gastric cancer with liver metastasis. Therefore, they would be
      excellent models for understanding the mechanism of metastatic growth and the
      development of a new molecular targeting therapy for gastric cancer with liver
      metastasis.

PMID- 16086235
TI  - Benzo-[a]-pyrene increases invasion in MDA-MB-231 breast cancer cells via
      increased COX-II expression and prostaglandin E2 (PGE2) output.
AB  - Benzo-[a]-pyrene (B[a]P), a carcinogenic component of cigarette smoke, has been
      shown to increase both COX-II expression and prostaglandin output in vascular
      smooth muscle and oral epithelial cells. In addition, invasive breast cancer
      cells have been reported to over express COX-II and PGE(2). Therefore, the
      objective of this study was to quantify the effect of increasing B[a]P
      concentrations on COX-II expression, PGE(2) output, and invasion using MDA-MB-231
      cells, an invasive estrogen unresponsive breast cancer cell line. B[a]P
      significantly increased invasion in MDA-MB-231 cells at concentrations greater
      than 4 x 10(-8) M. Treatment of MDA-MB-231 cells with Vomitoxin (a selective COX
      II inducer) enhanced invasion whereas co-treatment with NS398 (a selective COX-II
      inhibitor) attenuated B[a]P-induced invasion in MDA-MB-231 cells.
      Immunohistochemical staining and Western blots demonstrated a significant B[a]P
      treatment-induced increase in both the number of COX-II immunopositive MDA-MB-231
      cells and COX-II protein levels. Moreover, B[a]P-treatment induced a profound (46
      fold) increase in PGE(2) production by MDA-MB-231 cells. The aryl hydrocarbon
      receptor (AhR) antagonists resveratrol (RES) and alpha-naphthaflavone (alpha-NF)
      had no effect on their own, whereas B[a]P-induced invasion was significantly
      inhibited by co-treatment with RES and alpha-NF. Our data demonstrate that B[a]P
      induced changes in invasion are mediated through augmented COX-II expression and
      PGE(2) production involving an AhR regulated pathway. Moreover, these results
      suggest a potential role for the AhR signalling pathway in breast cancer
      invasion.

PMID- 16086236
TI  - Trefoil factor family-3 is associated with aggressive behavior of colon cancer
      cells.
AB  - BACKGROUND AND AIM: Trefoil factor family 3 (TFF3) is expressed by intestinal
      epithelial cells and it mainly functions to protect the mucosa from injury.
      Expression of TFF3 has been correlated with a poor prognosis in patients with
      cancer, but little is known about whether TFF3 directly contributes to the
      malignant behavior of cancer cells. The present study was conducted to determine
      whether TFF3 expression contributes to the malignant behavior of cancer cells in
      vitro and in vivo. METHODS: Two subclones of a metastatic rat colorectal cancer
      cell line, demonstrated previously to manifest aggressive (LN cells) and non
      aggressive (LP cells) growth in vivo, were analyzed for expression of TFF3 and
      tested in assays of cancer cell migration, invasion, and apoptosis in vitro, and
      mortality in vivo. RESULTS: The aggressive LN cell line endogenously expressed
      TFF3 and supported the transcription of a TFF3 promoter-driven reporter
      construct, whereas the non-aggressive LP cell line did not express TFF3. LN cells
      demonstrated enhanced migration, invasion, and less apoptosis compared to LP
      cells. Transfecting TFF3 into LP cells enhanced their ability to migrate, invade,
      block apoptosis, and behave more aggressively in vivo, thereby resembling the
      phenotype of LN cells. CONCLUSIONS: In rat colon cancer cells, both endogenous
      and constitutive expression of TFF3 correlates with an aggressive phenotype.
      These data provide direct evidence that TFF3 contributes to the malignant
      behavior of cancer cells.

PMID- 16086237
TI  - Distinct and opposite roles for SH2 and SH3 domains of v-src in embryo survival
      and hemangiosarcoma formation.
AB  - The cellular proto-oncogene c-src is thought to be involved in formation,
      progression, and metastasis of a variety of tumor cell types, although its exact
      role during tumor cell genesis is not well defined. v-src, the viral oncogene
      counterpart of c-src, causes metastatic sarcomas, hemorrhagic disease, and
      hemangiosarcomas in chicken embryos and, thus, can be used as a constitutively
      activated form of src for experimentally-induced tumorigenesis. Here, we used
      retroviral vectors to express wild-type v-src or SH2 or SH3 domain-deleted forms
      (DeltaSH2 or DeltaSH3) to determine if different pathogenic effects resulted.
      Vectors were injected into early chick embryo midbrain ventricles and embryos
      were sacrificed at various ages up to embryonic day (E) 18. Retroviral expression
      of all forms of v-src resulted in transformation of pial connective tissue cells
      into large, rounded abnormal-appearing cells. Surprisingly, all forms of v-src
      were lethal. The v-src retrovirus was lethal and killed most embryos by E15 with
      the development of hemangiosarcomas over the injection site between E10-E12. The
      DeltaSH3 retrovirus was the most deadly, killing most embryos by E12, however, it
      never resulted in hemangiosarcoma formation. The DeltaSH2 retrovirus injected
      embryos survived longer than v-src or DeltaSH3 embryos, and some of these embryos
      also developed large hemangiosarcomas over the injection site between E13 and
      E18. These results demonstrate that the src SH2 domain is required to be fully
      lethal, whereas the presence of the SH3 domain attenuated lethality. Furthermore,
      the formation of hemangiosarcomas absolutely required the presence of the src SH3
      domain and to some extent required the SH2 domain. This implicates distinct and
      opposite roles for SH2 and SH3 domains of src and their cellular binding partners
      in tumorigenesis and hemorrhagic disease.

PMID- 16086238
TI  - Statistical kinematics of axillary nodal metastases in breast carcinoma.
AB  - The number of involved lymph nodes in individuals with breast cancer is highly
      variable, and of both prognostic and therapeutic importance. A statistical
      description for the frequency distribution of the numbers of involved nodes in an
      affected population could potentially reveal mechanisms of axillary metastasis,
      and eventually facilitate predictive models for tumor control and axillary
      sampling. A meta-analysis of 15 studies involving 24,757 axillary dissections was
      performed, including conventional dissections, sentinel node dissections and
      studies of occult metastases. Frequency histograms for the numbers of involved
      axillary lymph nodes from the populations were tested for clustering and they
      were fitted, as a first approximation, to a negative binomial distribution.
      Although the number of involved nodes per individual was quite variable, some
      individuals sustained more involved nodes than could be expected from a random
      (Poisson) distribution. The negative binomial distribution, however, provided
      acceptable descriptions for the distributions of involved nodes in all
      populations studied. Two mechanisms could explain these observations: (1) an
      apparent contagion model, where involved nodes seeded further nodal metastases,
      and (2) a spurious contagion model where the number of involved nodes per
      individual was randomly (Poisson) distributed and population heterogeneity
      accounted for the more severe cases. Both models were consistent with the
      hypothesis that the nodal metastasis is a chance event, with the probability of
      involvement greatest for nodes contiguous to the primary tumor and proportioned
      by lymphatic flow.

PMID- 16086240
TI  - Design and expression of oligomeric fibronectin fusion protein: a strategy for
      enhancing cell adhesion activity.
AB  - Cell adhesion to extracellular matrices, including fibronectin, results in
      clustering of integrins in focal adhesions. To promote the clustering of
      fibronectin and thus enhance its activity at the sites of focal adhesion
      formation, we have engineered a fusion protein containing recombinant fibronectin
      fragment (hFN) connected to the tetramerization helix domain of lac repressor for
      oligomeric assembly. Purified Lac-hFN fusion protein exhibited significant
      increase of cell adhesion and proliferation of GF cells compared with hFN alone
      (p < 0.05).

PMID- 16086239
TI  - An orthotopic model of lung cancer to analyze primary and metastatic NSCLC growth
      in integrin alpha1-null mice.
AB  - The role of matrix metalloproteinase (MMP)9 in lung cancer progression is
      controversial. MMP9 promotes local tumor progression and distant metastasis in
      mouse models by enhancing extracellular matrix degradation, releasing VEGF from
      extracellular matrix and promoting vascular pericyte recruitment. Furthermore,
      increased plasma MMP9 expression levels in human subjects with metastatic non
      small cell lung cancer (NSCLC) inversely correlates with survival. In contrast,
      MMP9 can benefit the host by generating inhibitors of endothelial cell
      proliferation such as angiostatin and NC1 domains of collagen IV. To better
      understand the role of host MMP9 on the primary growth and metastatic potential
      of NSCLC, we performed an orthotopic model of NSLC in integrin alpha1-null mice
      (a genetic model for increased MMP9). In these mice we observed decreased number,
      size and vascularization of primary NSCLC tumors when compared to wild type
      controls. In addition, decreased number and size of NSCLC-derived metastases were
      evident in the alpha1-null mice. Furthermore, pharmacological inhibition of MMPs
      in the alpha1-null mice at the time of tumor cell injection resulted in an
      increase in the number of both primary and metastatic lung cancer as compared to
      untreated mice, suggesting that primary growth and metastases of NSCLC are
      worsened by the early inhibition of MMPs. In conclusion, although MMP9 may
      potentially promote tumor growth and metastasis, production of MMP-dependent anti
      angiogenic factors seems to override these effects and protects the host from
      NSCL growth and progression.

PMID- 16086241
TI  - Cloning and characterization of a bile salt hydrolase (bsh) from Bifidobacterium
      adolescentis.
AB  - A gene coding for bile salt hydrolase (BSH) from Bifidobacterium adolescentis was
      cloned and expressed in Escherichia coli, and the nucleotide sequence was
      determined. The BSH of E. coli transformants was produced intracellularly in the
      absence of bile salts. A unique bsh promoter (P(bsh)) sequence was identified by
      using a Neural Network Promoter Prediction (NNPP, version 2.2). In spite of their
      high-level sequence homology with other bsh genes in the Bifidobacterium species,
      their genetic organization surrounding the bsh gene and their promoter sequences
      are different depending on the species.

PMID- 16086242
TI  - Development of a murine prostatespecific 2-in-1 inducible bicistronic expression
      vector.
AB  - Transgenic research often suffers from the lack of strong tissue specific
      promoters and the lack of suitable antibodies for transgene detection. We have
      now constructed a novel prostate specific 2-in-1 Tetracycline-off (Tet-off),
      bicistronic expression vector, designated PbTetOIE, for transgenic research. The
      vector allows potent induction as well as inducible suppression of transgene
      expression in the prostate epithelial cells, and also allows the detection of
      transgene expression at the cellular level through the detection of the internal
      enhanced green fluorescent protein (EGFP) downstream of the transgene.

PMID- 16086243
TI  - Inhibition of Colorado potato beetle larvae by a locust proteinase inhibitor
      peptide expressed in potato.
AB  - The cDNA for a 73-mer peptide containing two locust serine proteinase inhibitors
      was cloned, fused to the constitutive CaMV35S promoter and introduced into potato
      by Agrobacterium-mediated transformation. From 23 independent transgenic lines,
      three with high mRNA level and proteinase inhibitory activity were propagated in
      vitro and transferred to pots. The peptide from the leaves was identified by its
      N-terminal sequence and by K(i) values against chymotrypsin and trypsin. Colorado
      potato beetle larvae reared on transgenic plants grew slightly but significantly
      more slowly than those on control plants. This supports the notion that
      expression of multifunctional proteinase inhibitors of insect origin might be a
      good strategy to improve insect resistance in plants.

PMID- 16086244
TI  - Ganoderic acid produced from submerged culture of Ganoderma lucidum induces cell
      cycle arrest and cytotoxicity in human hepatoma cell line BEL7402.
AB  - Ganoderic acid (GA), produced by submerged culture of Ganoderma lucidum, at 500
      microg/ml, caused nearly a 70% inhibition of the growth of human hepatoma cell
      line BEL7402 but not of a normal human liver cell line L02. Flow cytometry
      analyses showed that GA blocked the BEL7402 cell cycle at the transition from G(1
      )to S phase.

PMID- 16086245
TI  - Induced accumulation of oleanolic acid and ursolic acid in cell suspension
      cultures of Uncaria tomentosa.
AB  - Increasing sucrose from 20 to 50 g l(-1) in Uncaria tomentosa cell suspension
      cultures enhanced ursolic acid and oleanolic acid production from 129 +/- 61 to
      553 +/- 193 microg g(-1) cell dry wt. The maximal concentration of both
      triterpenes (1680 +/- 39 microg g(-1) cell dry wt) was 8 days after elicitation
      by jasmonic acid, while yeast extract or citrus pectin treatments produced 1189
      +/- 20 or 1120 +/- 26 microg g(-1) cell dry wt, respectively. The ratio of
      ursolic acid:oleanolic acid was constant at 70:30.

PMID- 16086246
TI  - Isolation and characterization of a white rot fungus Bjerkandera sp. strain
      capable of oxidizing phenanthrene.
AB  - Strain BOL13 was selected from 18 fungal strains isolated from an oil-spill
      contaminated site in Oruro, Bolivia. It was identified as a basidiomycete with
      high homology to Bjerkandera. The fungus degraded 100 mg phenanthrene l(-1) at
      0.17 mg l(-1) d(-1) at 30 degrees C at pH 7. During phenanthrene degradation, a
      maximum manganese peroxidase activity of 100-120 U l(-1) was measured after 10
      days of incubation. The ability of Bjerkandera sp. to produce lignin-modifying
      enzymes and to oxidize phenanthrene under various pH and temperature conditions
      was confirmed.

PMID- 16086247
TI  - Cloning and characterization of the gene encoding phosphoketolase in Leuconostoc
      mesenteroides isolated from kimchi.
AB  - The gene encoding phosphoketolase, which is 2749 bp long and contains 814 amino
      acid polypeptides with a total molecular mass of 91.9 kDa, was cloned from
      Leuconostoc mesenteroides C7 (LMC7) and expressed in Escherichia coli. It
      exhibited a homology of >58% with phosphoketolases from other lactic acid
      bacteria. The phosphoketolase of LMC7 belongs to the xylulose 5-phosphate
      (X5P)/fructose 6-phosphate (F6P) phosphoketolase (Xfp) family, which is an enzyme
      with dual specificity for X5P and F6P. The members of this family contain typical
      thiamin pyrophosphate (TPP) binding sites as reported for other TPP-dependent
      enzymes, and several highly conserved regions as signature patterns for
      phosphoketolases. The plasmid pGPK containing the Xfp gene (xfp) exhibits
      phosphoketolase activity in E. coli. The specific activities of the enzyme from
      E. coli BL21 and E. coli EC101 harboring xfp were 0.28 and 0.14 units/mg,
      respectively. They both exhibited a 1.5-fold increase in the production of acetic
      acid from acetyl phosphate compared with their corresponding original strain.

PMID- 16086248
TI  - alpha,omega-Dicarboxylic acid accumulation by acyl-CoA oxidase deficient mutants
      of Yarrowia lipolytica.
AB  - alpha,omega-Dicarboxylic acid accumulation from alkanes and alkane degradation
      intermediates was investigated using Yarrowia lipolytica wild type strain W29 as
      well as a double, a triple and a quadruple POX-deleted strains. Six genes, POX1
      through POX6, encode six acyl-CoA oxidase isozymes in Y. lipolytica. All the
      strains accumulated dodecanedioic acid (5-20 mg ml(-1)) from the diterminal
      functionalised 1,12-dodecane diol and 12-hydroxdodecanoic acid. The quadruple
      deleted strain was the only strain that was able to accumulate dioic acids from
      C16 alkanol and monocarboxylic acid as well as from C12, C14 and C16 alkanes
      (maximum 8 mg ml(-1) from dodecane).

PMID- 16086249
TI  - Characteristics of fed-batch cultures of recombinant Escherichia coli containing
      human-like collagen cDNA at different specific growth rates.
AB  - Fed-batch cultures of recombinant Escherichia coli BL21 for producing human-like
      collagen were performed at different specific growth rates (0.1 approximately
      0.25 h(-1)) before induction and at a constant value of 0.05 h(-1) after
      induction by the method of pseudo-exponential feeding. Although the final biomass
      (around 69 g l(-1)) was almost the same in all fed-batch cultures, the highest
      product concentration (13.6 g l(-1)) was achieved at the specific growth rate of
      0.15 h(-1) and the lowest (9.6 g l(-1)) at 0.25 h(-1). The mean productivity of
      human-like collagen was the highest at 0.15 h(-1) (0.57 g l(-1)h(-1)) and the
      lowest at 0.1 h(-1) (0.35 g l(-1 )h(-1)). In the phase before induction, the cell
      yield coefficient (Y(X/S)) decreased when the specific growth rate increased,
      while the formation of acetic acid increased upto 2.5 g l(-1) at 0.25 h(-1). The
      mean product yield coefficient (Y(P/S)) also decreased with specific growth rate
      increasing. The respiration quotient (RQ) increased slightly with specific growth
      rate increasing before induction, and the mean value of RQ was around 72%. The
      optimum growth rate for human-like collagen production was 0.15 approximately 0.2
      h(-1).

PMID- 16086250
TI  - De-repression and comparison of oil-water separation activity of the
      dibenzothiophene desulfurizing bacterium, Mycobacterium sp. G3.
AB  - Expression of the desulfurization genes (dsz) in Mycobacterium sp. G3 is
      repressed by sulfate, which is the product of biodesulfurization. An expression
      clone, pSMTABC, was constructed by placing the dsz genes downstream of the hsp60
      promoter and the constructed plasmid was electroporated into G3. The recombinant
      strain G3-1 desulfurized dibenzothiophene in the presence of 0.5 mM: sulfate
      while the Dsz phenotype was completely repressed in the wild-type strain.
      However, there was no significant increase in the amount of desulfurization
      enzymes in G3-1. In addition, G3 had superior separation of diesel oil-water
      separation activity compared to E. coli, which is superior to desulfurizing
      rhodococci.

PMID- 16086251
TI  - Simultaneous detection of double-stranded RNA-induced protein kinase and its
      specific mRNA by single cell analysis.
AB  - Fluorescent in situ hybridization was combined with flow cytometry to detect the
      expression of the double-stranded-RNA-induced protein kinase (PKR) in single
      cells. Labeled anti-sense oligonucleotide was used to target the specific mRNA
      while the protein was targeted with an antibody. It was demonstrated that the PKR
      mRNA signal could be protected through a lengthy immunostaining procedure. The
      expression pattern of the PKR-mRNA with respect to DNA content was shown to be
      comparable to that of 18S ribosomal RNA.

PMID- 16086253
TI  - The putative lipase, AF1763, from Archaeoglobus fulgidusis is a carboxylesterase
      with a very high pH optimum.
AB  - The open reading frame AF1763, annotated as a putative lipase gene (lipA) of the
      hyperthermophilic archaeon, Archaeoglobus fulgidus DSM 4304, was cloned and over
      expressed in E. coli. A sequence analysis of LipA and the investigation of a
      truncated enzyme implied a special function of the C-terminal part of LipA. The
      substrate spectrum of the enzyme suggested that LipA is a carboxylesterase rather
      than a canonical lipase. The enzyme showed optimal activity at 70 degrees C and
      between pH 10 and 11, which is among the most alkaline pH range detected for
      hydrolases.

PMID- 16086254
TI  - Stimulation of human hair growth by the recombinant human keratinocyte growth
      factor-2 (KGF-2).
AB  - Keratinocyte growth factor-2 (KGF-2) is found in dermal papilla fibroblasts and
      its receptor, fibroblast growth factor receptor 2 (FGFR2), in the neighboring
      outer root sheath of keratinocytes. Administration of recombinant human KGF-2
      (rhKGF-2) at 10 ng ml(-1) significantly stimulated human hair-follicle cell
      proliferation in organ culture (26-35%). Thus, rhKGF-2 is a promising therapeutic
      agent to stimulate human hair growth.

PMID- 16086255
TI  - Enzymatic biobleaching of two recalcitrant paper dyes with horseradish and
      soybean peroxidase.
AB  - A stilbene dye (Direct Yellow 11) and a methine dye, Basazol 46L, recalcitrant to
      common chemical bleaches, were treated with horseradish and soybean peroxidases.
      Both enzymes were effective at chromophore removal. When compared to laccase in
      combination with a mediator (ABTS), soybean peroxidase was more effective at
      oxidative dye removal, especially for the methine dye.

PMID- 16086256
TI  - Screening of catalytically active microorganisms for the synthesis of 6-modified
      purine nucleosides.
AB  - Modified nucleosides can be prepared by microbial transglycosylation from cheaper
      nucleoside precursors using free or immobilised whole cells. An efficient
      screening method to find transglycosylation activity in microorganisms was
      developed for the synthesis of 6-modified purine nucleosides, such as 6-chloro-,
      6-methoxy-, 6-iodo- and 6-mercaptopurine ribonucleoside. Out of 100
      microorganisms screened, Bacillus stearothermophilus ATCC 12980 was the best for
      this purpose.

PMID- 16086257
TI  - Transformation of ginsenosides Rb1 and Re from Panax ginseng by food
      microorganisms.
AB  - Ginsenosides Rb1 and Re, respectively belonging to the major protopanaxadiol and
      protopanaxatriol ginsenosides, were transformed using cell-free extracts from
      food microorganisms. Rb1 was transformed into compound K via Rd and F2 by
      Bifidobacterium sp. Int57, Bif. sp. SJ32, Aspergillus niger and A. usamii.
      Lactobacillus delbrueckii, and Leuconostoc paramesenteroides transformed Rb1 into
      Rh2 via Rd and F2. Bifidobacterium sp. SH5 transformed Rb1 into F2 via Rd. Re was
      transformed into Rh1 via Rg2 by Bif. sp. Int57 and Bif. sp. SJ32. A. niger
      transformed Re into Rh1 via Rg1. A. usamii transformed Re into Rg2.
      Transformation of Rb1 proceeded at a higher rate and needed less amount of
      enzymes than that of Re. Taken together, these processes would allow a specific
      bioconversion process possible to obtain specific ginsenosides using an
      appropriate combination of ginsenoside substrates and specific microbial enzymes.

PMID- 16086258
TI  - Nitrification and denitrification in high-strength ammonium by Alcaligenes
      faecalis.
AB  - Alcaligenes faecalis sp. No. 4, that has the ability of heterotrophic
      nitrification and aerobic denitrification in high-strength ammonium at about 1200
      mg-N/l, converted about one-half of removed NH4+-N to intracellular nitrogen and
      nitrified only 3% of the removed NH4+. From the nitrogen balance, 40-50% of
      removed NH4+-N was estimated to be denitrified. Production of N2 was confirmed by
      GC-MS and 90% of denitrified products was N2. The maximum ammonium removal rate,
      29 mg-N/l h and its denitrification rate in aerated batch experiments, were 5-40
      times higher than those of other bacteria with the same ability.

PMID- 16086259
TI  - Lycopene-epsilon-cyclase pre-mRNA is alternatively spliced in Cara Cara navel
      orange (Citrus sinensis Osbeck).
AB  - Lycopene-epsilon-cyclase is one of the key enzymes related to alpha-carotene
      metabolism in plants. A full-length cDNA of 1300 bp encoding lycopene-epsilon
      cyclase (Lyce) was generated from Cara Cara navel orange, a unique navel orange
      containing both lycopene and beta-carotene in its pulp, with little or no alpha
      carotene. The gene had a 14 bp nucleotides deletion and caused a terminal
      mutation. DNA sequence corresponding to the deletion region revealed that two
      repeats of 6 bp (AGGTGT) were flanking the region in both Cara Cara and its
      original variety, Washington navel oranges, but a 2 bp (AT) insertion was only
      found in Cara Cara which explain the alternative splicing character of the gene.

PMID- 16086260
TI  - Pilot-scale fermentation and purification of the recombinant allophycocyanin over
      expressed in Escherichia coli.
AB  - A recombinant allophycocyanin (rAPC), used for treatment of tumors, has been
      expressed in E. coli which was grown in glucose fed-batch culture in a 30 l
      fermentor. Recombinant allophycocyanin was purified from soluble E. coli cell
      lysate using hydrophobic interaction chromatography followed by chromatography
      using amylose affinity column. The purity of product was greater than 98% and
      yielded an average of 5.5 g kg(-1) dry cells. Recombinant allophycocyanin
      significantly inhibited H22 hepatoma (p ( 0.01) in mice with inhibition rates
      ranging from 36% to 62% with doses from 6.25 to 50 mg kg(-1) d(-1).

PMID- 16086261
TI  - Regioselective enzymatic synthesis of non-steroidal anti-inflammatory drugs
      containing glucose in organic media.
AB  - Enzymatic transesterification of glucose with the vinyl ester of non-steroidal
      anti-inflammatory drugs (NSAIDs) was in organic media performed for synthesis of
      novel NSAIDs-glucose conjugates. Glucose was regioselectively acylated at the 6
      hydroxyl group. The indomethacin-glucose conjugate and ketoprofen-glucose
      conjugate were produced by the catalysis of alkaline protease from Bacillus
      subtilis in the respective yields of 42% (over 48 h) and 63% (over 40 h). The
      etodolac-glucose conjugate was obtained in 26% yield (over 144 h) by lipase from
      Candida antarctica.

PMID- 16086262
TI  - Biotransformation of alpha-santonin by cell suspension cultures of five plants.
AB  - Cell suspension cultures of five plants (Catharanthus roseus, Ginkgo biloba,
      Platycodon grandiflorum, Taxus cuspidata, Phytolacca asinosa) were employed to
      bioconvert the eudesmanolide compound, alpha-santonin. Reactions occurring were
      hydroxylation (C-1, C-11 and C-15), reduction of the double bond [1(2) or 3(4)],
      rearrangment of the eudesmanolide skeleton to a guaianolide skeleton and lactone
      ring hydrolysis. Four new compounds were identified.

PMID- 16086263
TI  - Characterization of a novel phosphoinositide-specific phospholipase C from Zea
      mays and its expression in Escherichia coli.
AB  - A cDNA encoding a phosphoinositide-specific phospholipase C (PI-PLC) has been
      isolated from Zea mays by screening a cDNA library. The cDNA, designated ZmPLC,
      encodes a polypeptide of 586 amino acids, containing the catalytic X, Y and C2
      domains found in all PI-PLCs from plants. Northern blot analysis showed that the
      expression of the ZmPLC gene in roots is up-regulated under conditions of high
      salt, dehydration, cold or low osmotic stress conditions. Recombinant ZmPLC
      protein was expressed in Esch- erichia coli, purified and used to produce
      polyclonal antibody, this polyclonal antibody is important for further studies to
      assess the ultimate function of the ZmPLC gene in plants.

PMID- 16086264
TI  - A Pitfall of the 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4
      sulfophenyl)-2H-tetrazolium (MTS) assay due to evaporation in wells on the edge
      of a 96 well plate.
AB  - The 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H
      tetrazolium (MTS) calorimetric assay is replacing the traditional 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as a fast, one
      step assay of cell viability. We have observed that evaporation of the outer
      wells of a 96 well plate increases the absorbancy by 52% compared to the inner
      wells. Filling the outer 2 rows of wells with media and replacement of the media
      prior to addition of the MTS reagent will, however, correct this inaccuracy.

PMID- 16086266
TI  - Does pulsatile urea excretion serve as a social signal in the gulf toadfish
      Opsanus beta?
AB  - This study evaluated the hypothesis that the pulsatile excretion of urea by
      toadfish could serve as a social signal. In the first experiment, physiological
      parameters were measured in pairs of dominant and subordinate toadfish.
      Subordinate toadfish had elevated concentrations of circulating plasma cortisol,
      an effect maintained even after cannulation. In the second experiment, one fish
      of a pair was injected with 14C-urea, and the occurrence of urea pulses during
      social encounters was documented. Social status did not influence the order of
      pulsing, that is, whether a dominant or subordinate fish pulsed first during a
      social encounter. However, in seven out of eight pairs, both toadfish pulsed
      within 2 h of each other, indicating some form of communication between fish. In
      the third and final experiment, the response of toadfish to urea (natural or
      synthetic) was observed. There was a tendency for toadfish to avoid synthetic
      urea but there was no apparent behavioural response to water containing toadfish
      urea. Pulsing events do not appear to play an integral role during social
      encounters as previously hypothesised, but the close timing of pulses in toadfish
      pairs suggests some transfer of information.

PMID- 16086267
TI  - Mutation analysis of small heat-shock protein 22 gene in Chinese patients with
      Charcot-Marie-Tooth disease.
AB  - OBJECTIVE: To study the characteristics of the mutation of small heat-shock
      protein 22 (HSP22) gene in Chinese patients with Charcot-Marie-Tooth (CMT)
      disease. METHODS: A CMT2L proband with 423(G--> T) mutation in HSP22 gene had
      been studied and reported by the present authors. In this study, mutation
      analysis of HSP22 gene was performed using polymerase chain reaction and DNA
      direct sequencing in 114 CMT probands. RESULTS: In the 114 CMT probands, a 582(C-
      > T)(T194T)samesense mutation was found in two unrelated families. CONCLUSION:
      The rate of HSP22 gene mutation in Chinese patients with CMT is as low as
      0.87%(1/115).

PMID- 16086268
TI  - Effects of preimplantation embryos on expressions of DNA methyltransferase 1 in
      mouse oviduct epithelial cells.
AB  - OBJECTIVE: To investigate the effects of mouse preimplantation embryos on the
      expressions of DNA methyltransferase 1(Dnmt1) of mouse oviduct epithelial cells.
      METHODS: The histological location of Dnmt1 protein was detected by
      immunohistochemical staining and the expression levels of Dnmt1 mRNA and protein
      in mouse oviduct were assayed by real-time reverse transcription-PCR(RT-PCR) and
      Western blotting in both pregnant and pseudopregnant mice at the 2-cell, 4-cell
      and 8-cell stages. RESULTS: The expressions of Dnmt1 protein were mainly located
      in the epithelial cells of mouse oviduct. It was found that during all three
      stages, the expression levels of Dnmt1 mRNA in the epithelial cells of the
      pregnant mice were significantly lower than those in the pseudopregnant mice (P<
      0.05), and the level of Dnmt1 protein expression in the pregnant mice was
      significantly decreased as compared with that in pseudopregnant mice at the 4
      cell stage. CONCLUSION: Expressions of both Dnmt1 mRNA and protein in the
      epithelial cells of mouse oviduct could be regulated by mouse preimplantation
      embryos, which might play an important role in the expression changes of some
      genes in oviduct epithelial cells during the preimplantation period.

PMID- 16086269
TI  - Sequence analysis of the mitochondrial genome from a large family with maternally
      inherited nonsyndromic deafness.
AB  - OBJECTIVE: To ascertain whether other variations coexist with 1555(A--> G)
      mutation in the mitochondrial DNA and may aggravate the severity of hearing loss
      or increase the penetrance of 1555(A--> G) mutation in a large family with
      maternally inherited nonsyndromic deafness in Huaiyin, Jiangsu province. METHODS:
      PCR-restriction fragment length polymorphism (PCR-RFLP) was used to screen both
      the nt1555 and the nt7445 of the mitochondrial DNA from 27 maternal members in
      the core family; and then the mitochondrial genomes from two maternal members,
      and the 12S rRNA genes MTRNR1 and tRNA-Ser(UCN) gene MTTS1 from the others, were
      amplified by PCR-RFLP and were sequenced. RESULTS: 1555(A--> G) mutation in the
      mitochondrial DNA was reverified to be one of the major factors which cause
      maternally inherited nonsyndromic deafness and the cosegregation of 955-960(insC)
      and 1555(A--> G) was present in this family. Moreover, 7449 (insG), a novel
      homoplasmic mutation in the tRNA-Ser(UCN) gene, was found to co-exist with 1555(A
      -> G) mutation in two maternal members. CONCLUSION: The cosegregation of 955
      960(insC) and 1555(A--> G) implies that 955-960(insC) may synergistically cause
      hearing loss in the presence of an 1555(A--> G) mutation, serving as an
      aggravating factor to enhance the sensitivity to aminoglycosides, and may
      sometimes increase the penetrance of 1555(A--> G) mutation.

PMID- 16086270
TI  - A novel mutation in the FOXL2 gene in a Chinese family with blepharophimosis,
      ptosis, and epicanthus inversus syndrome.
AB  - OBJECTIVE: To screen mutations in the forkhead transcriptional factor 2 gene
      (FOXL2) in six Chinese families with blepharophimosis, ptosis, and epicanthus
      inversus syndrome(BPES). METHODS: PCR amplification and direct sequencing of the
      FOXL2 coding region in genomic DNA were performed in affected patients and 80
      healthy controls. BLAST analysis of the sequence was made on Internet. RESULTS: A
      novel 951-953(delC) was found in the two affected patients of a Chinese family
      with BPES. No mutations were found in the healthy controls. The 951-953(delC) may
      cause a frameshift mutation after codon 238 that exists downstream of the
      forkhead domain, resulting in the production of truncated proteins. CONCLUSION:
      These findings indicated that the 951-953(delC) deletion mutation in the two
      patients resulted in truncated proteins and hence led to their BPES. To the
      authors' knowledge, the 951-953(delC) in FOXL2 has not been previously reported.

PMID- 16086271
TI  - Molecular analysis of SLC26A4 gene in a Chinese deafness family.
AB  - OBJECTIVE: To identify the pathogenic gene for a non-syndromic hearing loss
      family. METHODS: Mutation analysis was carried out by polymerase chain reaction
      and direct sequencing of all exons of SLC26A4 (solute carrier family 26, member
      4) gene. RESULTS: Compound heterozygous mutations N392Y and S448X were detected
      in the proband of the family, heterozygous mutation S448X was detected in the
      father, heterozygous mutation N392Y was detected in the mother. CONCLUSION: The
      proband's hearing loss resulted from the compound heterozygous mutations N392Y
      and S448X for SLC26A4 gene.

PMID- 16086272
TI  - Polymorphism of the D4Z4 locus associated with facioscapulohumeral muscular
      dystrophy 1A in Shanghai population.
AB  - OBJECTIVE: To investigate the D4Z4 repeats on chromosome 4q35 in normal
      individuals in Shanghai and analysis the polymorphism of the D4Z4 locus. METHODS:
      The length of D4Z4 repeats on chromosome 4q35 in 191 normal individuals in
      Shanghai was determined by pulsed-field gel electrophoresis and Southern blotting
      after double digestion with Eco RI and Bln I. The number of short D4Z4 repeats
      was counted after partial digestion with Kpn I. RESULTS: Among 191 normal
      individuals in Shanghai, seventeen showed the size of D4Z4 fragments ranged from
      22 to 34 kb, i.e. 8.9% of individuals had fewer numbers of D4Z4 repeats. Of these
      17 individuals, sixteen showed the short D4Z4 fragment on chromosome 4q35, and
      one low D4Z4 fragment was correlated to 4q35--> 10q26 translocation. CONCLUSION:
      The frequency of individuals having fewer numbers of D4Z4 repeats on chromosome
      4q35 in Shanghai population is higher than that in Caucasian population although
      the short D4Z4 fragment on chromosome 4q35 is associated with facioscapulohumeral
      muscular dystrophy. These findings suggest that other factors may also contribute
      to facioscapulohumeral muscular dystrophy.

PMID- 16086273
TI  - Effect of caspase 9 related signaling molecules on the apoptosis of human
      vascular endothelial cell induced by homocysteine.
AB  - OBJECTIVE: To understand the role of mitochondria associated signaling pathway in
      the apoptosis of human vascular endothelial cell induced by homocysteine (Hcy).
      METHODS: The mRNA and protein expression levels of the up-stream signaling
      molecules of caspase 3, Bcl 2, caspase 9, and cytosolic cytochrome-c, were
      investigated. The in vitro cultured human umbilical vein endothelial cells with
      homocysteine at different concentrations were incubated for 24 h. The expressions
      of Bcl 2 and caspase 9 at mRNA and protein levels were analyzed by reverse
      transcription-polymerase chain reaction(RT-PCR) and Western blot. Cytochrome-c in
      cytoplasm was also detected by Western blot. RESULTS: The expression levels of
      three signaling molecules were all down-regulated by homocysteine at both mRNA
      and protein levels in a dose-dependent manner. CONCLUSION: Homocysteine could
      affect the formation of apoptosome through repressing the expression of Bcl 2
      gene and release of cytochrome-c from mitochondria. Decreasing of apoptosome
      could disturb the activation of caspase 9. The results also indicate that the
      mitochondria pathway is not the major signaling pathway involved in Hcy-induced
      apoptosis.

PMID- 16086274
TI  - Study on the relationship between G1057D variants of IRS2 gene and obese T2DM in
      Chinese Han subjects.
AB  - OBJECTIVE: To investigate the relationship between the G1057D variants of insulin
      receptor substrate-2(IRS2) gene and type 2 diabetes mellitus (T2DM) in subjects.
      METHODS: Four hundred and thirty-nine Chinese Han subjects, including 218
      patients with T2DM and 221 normal controls, were selected from the Hans in the
      Liaoning area, and each group was divided into two subgroups according to body
      mass index. The G1057D variants of IRS2 were detected by polymerase chain
      reaction-restriction fragment length polymorphism(PCR-RFLP) and their
      relationships with T2DM were analyzed. RESULTS: (1) The frequency of G1057D
      variant was 29% in all subjects. The frequency of DD genotype was significantly
      lower in non-obese DM group than in non-obese control group. The Logistic
      regression analysis showed that the odds ratio of DD genotype was 0.265. The
      frequency of DD genotype was significantly higher in obese DM group than in obese
      control group. The Logistic regression analysis showed that the odds ratio of DD
      genotype was 3.991. (2) In the non-obese control group, the FPG and 2hCP of DD
      genotypes were lower than those of GG genotypes (P< 0.05, P< 0.01), the HOMA-B of
      DD genotypes was higher than that of GG genotype (P< 0.01). In the non-obese DM
      group, the waistline/hip ratio (WHR) of DD genotypes was higher than that of GG
      genotypes(P< 0.01). In the obese DM group, the WHR, HOMA-IR, 2hPG, 2hINS and 2hCP
      levels of DD genotypes were higher than those of GG genotypes, while the level of
      HOMA-B of DD genotypes was lower than that of GG genotypes. In the obese control
      group, the WHR, HOMA-IR, 2hPG, 2hINS and 2hCP levels of DD genotype were higher
      than those of GG genotype, and the HOMA-B level of DD genotype was lower than
      that of GG genotypes (P< 0.05). CONCLUSION: The relationships between G1057D
      variants of IRS2 and T2DM are mediated by obesity.

PMID- 16086275
TI  - Closely linked polymorphic marker: successful application in preimplantation
      genetic diagnosis for beta-thalassemia.
AB  - OBJECTIVE: To evaluate the applicability of the polymorphic marker closely linked
      with beta-globin gene for the preimplantation genetic diagnosis (PGD) in couples
      at risk of having child with beta-thalassemia. METHODS: Single cell multiplex
      nested PCR which coamplifies the beta-globin gene and the closely linked
      polymorphic marker, HumTHO1 gene, was applied in six clinical PGD cycles for four
      couples with beta-thalassemia. RESULTS: In six clinical PGD cycles, a total of 44
      embryos were biopsied and 44 blastomeres were obtained. Forty-one blastomeres
      were amplified and thirty-five embryos were given definite diagnoses. Fourteen
      embryos were transferred back to the uterus of the patients and one pregnancy
      went on well and ended with one live healthy birth, which confirmed the results
      of PGD. The average amplification efficiency of single blastomere was 89.7% and
      the average allele drop-out(ADO) rate was 14.4%. The coamplification of HumTHO1
      could help to detect the existence of ADO and contamination. CONCLUSION: This is
      the first report on unaffected pregnancy resulting from PGD using multiplex
      nested PCR in China. The simultaneous amplification of polymorphic marker closely
      linked to beta-globin gene(HumTHO1) could help to resist the risk of misdiagnosis
      in PGD caused by ADO and contamination.

PMID- 16086276
TI  - A novel RPGR gene mutation in a Chinese family with X-linked dominant retinitis
      pigmentosa.
AB  - OBJECTIVE: To report a novel mutation in RPGR gene in a Chinese family with X
      linked dominant retinitis pigmentosa(XLRP). METHODS: Genetic linkage analysis was
      performed on the known genetic loci for XLRP with a panel of polymorphic markers,
      then the mutations were identified by single-strand conformation
      polymorphism(SSCP) and direct sequencing. RESULTS: Significant two-point Lod
      score was generated using marker DXS8025 (Zmax=2.4, theta =0). The disease gene
      locus was confined to Xp21.1 with further analysis of genetic linkage and
      haplotype. Mutations screening of RPGR gene in this family revealed a GA deletion
      at ORF15+483-484 which caused the open reading frameshift. This novel mutation co
      segregated with the affected members of the pedigree, but it was not present in
      the unaffected relatives. CONCLUSION: The above finding expands the spectrum of
      RPGR mutations causing XLRP in Chinese family and is useful for further genetic
      consultation and genetic diagnosis.

PMID- 16086277
TI  - [Therapy of Duchenne muscular dystrophy with umbilical cord blood stem cell
      transplantation].
AB  - OBJECTIVE: To analyze a Duchenne muscular dystrophy(DMD) patient's muscular
      regeneration, dystrophin expression and locomotive variation before and after he
      underwent umbilical cord blood stem cell transplantation in order to assess the
      therapeutic effect. METHODS: A 12-year-old DMD boy who could not walk for 3 years
      was confirmed by gene analysis and dystrophin protein immune test on his muscle.
      He had no other chronic disease. By HLA matching, a piece of umbilical cord blood
      stem cell with 6 HLA sites matching to the boy was found in Guangdong Umbilical
      Cord Blood Bank. The number of the nucleated cells of the umbilical cord blood
      stem cell was 24.08x 10(8). After pretreatment for the DMD boy with busulfan,
      cyclophosphamide and rabbit anti-human thymocyte globulin, the allergenic cord
      blood stem cells were transplanted into him by intravenous injection. Cyclosporin
      A, methylprednisolone, MMF, prostaglandin E1 and ganciclovir were given after the
      transplantation. At the same time, Gran, the granulocytic cell stimulating
      factor, and gamma globulin were administered. The biochemistry profile including
      serum creatine kinase (CK), the reconstruction of blood making, the deletion exon
      of DMD gene, the regenerating muscles, the dystrophin protein expression, and the
      locomotive function of the DMD boy were tested regularly. RESULTS: (1) The white
      blood cells (WBC) of peripheral blood decreased gradually to zero after
      pretreatment. In a period of 15 days after transplantation, the neutrophil
      increased to 0.5x 10(9)/L; at 25 days, WBC increased to normal level. Blood
      platelet was more than 20x 10(9)/L at 22 days. The hemoglobin rose to 85-100 g/L.
      At 140 days, sternal puncture revealed the rapid growth of neutrophil, blood
      platelet and hemoglobin. (2)At 140 days, the blood type of the DMD boy
      transformed from type O to type AB (the donor's blood type being AB). There was
      no grafe versus host reaction. (3) At 18, 30, 43, 55, 74 and 233 days after
      transplantation, the PCR-short tandem repeat test of the boy's peripheral blood
      DNA showed that his genotype was completely the same as the donor's. The results
      of PCR-short tandem repeat tests of the bone marrow cells DNA by sternal puncture
      at 140, 183 and 235 days were the same as those of the blood DNA. (4) At 60 days,
      DMD gene analysis by PCR showed that the defected DMD gene (exon 19 deletion) had
      been corrected by the umbilical cord stem cells transplantation. (5) At 75 days,
      the biopsy of calf muscle showed there were myoblast cells and muscular tubes
      growing. The dystrophin expressions were weak, but a few of them were strong. DNA
      analysis showed that the donor's gene DNA accounted for 1%-13%. At 126 days,
      obviously increased dystrophin positive muscular fibers of the boy were found.
      The donor's fibers rose to 2.5%-25%. (6) The serum CK of the boy declined from
      5735 U/L to 274 U/L. (7) At 100 days, physical examination revealed improvement
      in his arms and legs. CONCLUSION: The therapy of Duchenne muscular dystrophy with
      allogeneic umbilical cord blood hematopoietic stem cell transplantation may reset
      up the blood-making function, decrease the serum CK level, restore the dystrophin
      in muscles, and improve the locomotive function of the DMD boy. These data
      suggest that the allogeneic umbilical cord blood hematopoietic stem cell
      transplantation may benefit the DMD boys.

PMID- 16086278
TI  - [Association of TNFA polymorphisms with the outcomes of HBV infection].
AB  - OBJECTIVE: To explore whether the TNFA promoter single nucleotide polymorphisms
      (SNPs) are associated with the outcomes of hepatitis B virus(HBV) infection in
      Chinese Han population. METHODS: One hundred and forty-eight self-limited HBV
      infection subjects and 207 chronic hepatitis B patients were recruited.
      Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      sequence specific primer-PCR(PCR-SSP) were used to detect the SNPs of five sites
      in TNFA promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency
      distributions of genotypes and haplotypes in different groups were analyzed by
      EPI and EH programs. RESULTS: The frequencies of -238GG genotype in chronic
      hepatitis B patients were significantly higher than that in self-limited
      infection subjects (P=0.02). The frequencies of -857TT genotype in chronic
      hepatitis B patients were clearly lower than that in self-limited infection
      subjects (P=0.02). Haplotypic frequencies of GGCCT (-238/-308/-857/-863/-1031) in
      chronic hepatitis B patients was significantly lower than that in self-limited
      infection subjects (P=0.03), and the frequencies of haplotype GGCAT or GGTAT in
      chronic hepatitis B patients were clearly higher than those in self-limited
      infection subjects (P=0.0001; P=0.004). CONCLUSION: TNFA promoter polymorphisms
      are important host genetic factors affecting the outcomes of HBV infection.

PMID- 16086279
TI  - [Study on the mechanism of oocyte aneuploidy by spectral karyotyping].
AB  - OBJECTIVE: To establish the method of detecting oocyte aneuploidy by spectral
      karyotyping (SKY). METHODS: The unfertilized oocytes were fixed 1-2 days after
      oocyte retrieval. Spectral karyotyping was performed according to the protocol.
      RESULTS: 64% of oocytes were normal, 36% of oocytes were aneuploidy, of which 22%
      were due to nondisjunction and 14% unbalanced predivision. CONCLUSION: SKY is an
      effective method for detecting oocyte aneuploidy. Both nondisjunction and
      unbalanced predivision are involved in oocyte aneuploidy formation.

PMID- 16086280
TI  - [Association of two exonic genetic polymorphisms in the DNA repair gene XPC with
      risk of lung cancer in Chinese population].
AB  - OBJECTIVE: To explore the relationship between two exonic polymorphisms of DNA
      repair gene XPC and the susceptibility to lung cancer. METHODS: Genotypes were
      determined by the primer introduced restriction analysis-PCR(PIRA-PCR) and the
      PCR-restriction fragment length polymorphism(PCR-RFLP) approaches, respectively,
      in 320 histologically-confirmed lung cancer cases and 322 age and sex frequency
      matched cancer-free controls. RESULTS: Multivariate logistic regression analysis
      revealed that individuals carrying at least one 499Val variant allele (Ala/Val +
      Val/Val genotypes) had a significantly increased risk for lung cancer (adjusted
      OR=1.54; 95%CI: 1.11-2.14), compared with the wild-type genotype (499Ala/Ala).
      Furthermore, individuals with both putative risk genotypes had a significantly
      higher risk (adjusted OR=2.55; 95%CI: 1.45-4.52), compared with those with both
      wild-genotypes. In addition, a potential super multiplicative gene-environment
      interaction between Ala499Val genotypes and smoking on lung cancer risk was
      unveiled. The odds ratios of lung cancer for individuals with both putative risk
      genotypes were 2.63 (95%CI=1.23-5.62) in nonsmokers and 7.36 (95%CI=3.19-17.0) in
      smokers, respectively. CONCLUSION: These findings support the hypothesis that
      these two XPC variants may contribute to the risk of developing lung cancer.

PMID- 16086281
TI  - [Functional analysis of novel mutations in PAX9 associated with familial
      oligodontia].
AB  - OBJECTIVE: To gain new insights into the molecular pathogenesis of the 109(InsG)
      and 139(C--> T) mutations and their roles in familial oligodontia. METHODS: The
      region of PAX9 paired domain (PAX9PD) was amplified and the expression plasmids
      were constructed in pGEXlambda -1T by PCR-based cloning. PAX9PD proteins were
      prepared on the basis of GST instruction. The binding of wild type and two novely
      mutant PAX9 paired domain to double-stranded DNA targets were analyzed by gel
      mobility shift assay. RESULTS: Wild type PAX9PD protein bind to the high affinity
      paired domain recognition sequences, CD19-2(A-ins) and Pax6CON, the 109(InsG) and
      139(C--> T) mutant PAX9PD protein were unable to bind to these cognate DNA
      binding sites. CONCLUSION: The functional defects in DNA binding of mutant
      109(InsG) PAX9 and 139(C--> T) PAX9, as well as loss-of-function of PAX9 most
      likely result in its haploinsufficiency during the patterning of dentition and
      the subsequent loss of posterior teeth.

PMID- 16086282
TI  - [Study on polymorphisms of CYP3A5 gene and their clinical role].
AB  - OBJECTIVE: To investigate the polymorphisms of CYP3A5 gene in Chinese population
      and the association between CYP3A5 genotypes and their clinical functions.
      METHODS: CYP3A5 gene varisances were detected in 180 samples using denaturing
      high-performance liquid chromatography(DHPLC), and CsA concentrations in 12 of
      180 samples from hemopoietic stem cell transplant recipients were monitored by a
      commercial fluorescence polarization immunoassay. The data were analyzed by a
      statistical software. RESULTS: In the 180 samples, there was only one allelic
      variant CYP3A5*3 with a frequency of 76.1% (274/360), and there were three CYP3A5
      genotypes, namely CYP3A5*1/*1, CYP3A5*1/*3 and CYP3A5*3/*3 with frequencies of
      5.6%, 36.7% and 57.8% respectively. Also, there were significant differences in
      CsA concentrations, including standardized trough concentrations C(0) and two
      hour peak concentrations C(2), between CYP3A5 CYP3A5*1/*1 and CYP3A5*1/*3 found
      in 12 hemopoietic stem cell transplant recipients, and both C(0) and C(2) in
      CYP3A5*1/*1 were lower than those in CYP3A5*1/*3. CONCLUSION: CYP3A5*3 is the
      primary allelic variant in Chinese population. CYP3A5 genotypes are closely
      associated with blood CsA concentrations in hemopoietic stem cell transplant
      recipients, and CYP3A5*1/*1 requires a larger CsA dose to maintain the same blood
      concentration than does CYP3A5*1/*1. CYP3A5 genotyping by DHPLC may predict
      recipients' phenotype and CsA dose requirement.

PMID- 16086283
TI  - [Recombination within the human leucocyte antigen].
AB  - Understanding with greater clearness the characteristics of recombination within
      the human leucocyte antigen(HLA) is of deep significance to gaining an insight
      into the evolutionary process of shaping HLA allelic diversity and ultimately the
      human resistance against diverse pathogens. Family studies and statistical
      analysis of recombination have provided estimations of recombination fractions
      across the major histocompatibility complex and have identified the potential
      recombination hotspots. Other characteristics such as haplotype specificity and
      sequence motifs have been intensively studied. The recombination fractions,
      hotspots and other characters are reviewed in this paper.

PMID- 16086284
TI  - [Suppression of enhanced green fluorescent protein expression in cells by RNA
      interference].
AB  - OBJECTIVE: To evaluate the role of RNA interference (RNAi) in silencing the
      enhanced green fluorescent protein (eGFP) expression in 293T and Mel cells.
      METHODS: Nested-PCR was used to amplify H1 promoter from human 293T cells for
      driving RNAi synthesis. RNAi vectors (TR1) for silencing the eGFP expression was
      constructed. The eGFP vector and RNAi vector (TR1) were then co-transfected into
      the 293T and Mel cells, in which the silencing effect on eGFP expression was
      investigated by fluorescence microscopy, reverse transcription-PCR(RT-PCR),
      fluorescence-assited cell sorting(FACS) analysis and real-time RT-PCR. RESULTS:
      RNAi could effectively reduce more than 50 percent of eGFP expression in 293T
      cells as well as in Mel cells. CONCLUSION: The RNAi vector constructed in this
      way paper can effectively inhibit eGFP expression in cells.

PMID- 16086285
TI  - [Marker chromosome analysis in Chinese patients with Turner syndrome by
      fluorescence in situ hybridization].
AB  - OBJECTIVE: To identify the origin of marker chromosome of patients with Turner
      syndrome, and to provide the information for genetic counseling and treatment.
      METHODS: The karyotypes of 32 patients with Turner syndrome from 2001 to 2003 at
      the Center for Diagnosis of Genetic Metabolic Diseases were reviewed. Metaphase
      chromosome analyses of peripheral blood lymphocytes, G-band and C-band were
      performed using standard methods. Fluorescence in situ hybridization (FISH) was
      performed to identify the origin of marker chromosome by using two probes: sex
      determining region Y (SRY) for band region Yp11.3 and chromosome enumeration
      probe for X(CEPX) for band region Xp11.1-q11.1. RESULTS: 3/32(9.4%) patients with
      Turner syndrome had marker chromosome, the karyotype being 45,X/46,X,mar. Among
      the 3 marker chromosomes, 2 originated from chromosome X or Y, as identified by
      the FISH. The origin of the third marker chromosome could not be identified by
      CEPX and SRY probes. CONCLUSION: The presence of a marker chromosome in Turner
      syndrome generally implicates a sex chromosome origin. It may also originate from
      a non-sex chromosome. Therefore, it is necessary to apply X and Y probes
      simultaneously for marker chromosome detection in Turner patients with monosomy
      X.

PMID- 16086286
TI  - [Tetrahydrobiopterin loading test in differential diagnosis among
      hyperphenylalaninemia patients].
AB  - OBJECTIVE: To perform tetrahydrobiopterin (BH(4)) loading test and to further
      understand its usefulness in differential diagnosis among
      hyperphenylalaninemia(HPA) patients. METHODS: BH(4) loading test was carried out
      in 73 HPA patients, including the positive cases unveiled by neonatal screening
      and the clinically suspected cases. These patients, 47 males and 26 females, were
      at a mean age of 1.93 months. BH(4) (20 mg/kg) loading test was performed in all
      patients, and a combined phenylalanine (Phe)(100 mg/kg) and BH(4) loading test
      was performed among the patient who had a basic blood Phe concentration less than
      600 micro mol/L. The urine pterine profile analysis and the dihydropteridine
      reductase activity in dry blood filter spot were tested simultaneously. RESULTS:
      During BH(4) loading test or combined Phe and BH(4) loading test, the patients
      with classic phenylketonuria showed no response to BH(4), the patients with
      moderate HPA caused by Phe hydroxylase deficiency decreased 32.8% of blood Phe
      level and the patients with BH(4) deficiency showed a prompt reduction in blood
      Phe level and it decreased to normal level at 4 h and lasted until 24 h. Twenty
      two cases were diagnosed as classic phenylketonuria, 39 were moderate
      phenylketonuria and 12 were BH(4) deficiency. CONCLUSION: Hyperphenylalaninemia
      may be caused by deficiency of Phe hydroxylase or by deficiency of co-factor
      BH(4). Early diagnosis is important. BH(4) loading test is a safe and fast test
      in vivo. It is sensitive, easy-to-do, and is highly useful in differential
      diagnosis for suspected cases of HPA.

PMID- 16086287
TI  - [Transmission disequilibrium analysis of 1137-1140 Del GTGA frameshift mutation
      within the KCNN3 gene and schizophrenia based on family trios].
AB  - OBJECTIVE: To investigate the relationship between 1137-1140 Del GTGA in exon 1
      at KCNN3 gene and schizophrenia. METHODS: The study included 289 subjects
      (affected 107; unaffected 182) from 95 schizophrenic trios. All subjects were
      collected from Han Chinese in south China and genotyped for 1137-1140 Del GTGA in
      KCNN3 using PCR and restriction endonuclease Dde I. All the affected patients met
      the CCMD-II-R criteria for schizophrenia. The haplotype-based haplotype relative
      risk(HHRR) and transmission/disequilibrium test(TDT) analyses were done in 95
      schizophrenic trios. RESULTS: Comparative analysis on the distribution of alleles
      between the affected and unaffected parents(87 family trios) showed no
      significant difference(X(2)=0.253, P> 0.05). HHRR showed that KCNN3 gene alleles
      transmitted to the patients were not different from that of the non-transmitted
      parental alleles(X(2)=0.042, P> 0.05). TDT revealed that A(2) alleles were not
      preferentially transmitted to schizophrenic patients(X(2)=3.000, P=0.0833).
      CONCLUSION: In this study a lower frequency for 1137-1140 Del homozygote of KCNN3
      gene was observed, and the HHRR and TDT analyses suggested that the 1137-1140 Del
      alleles of KCNN3 gene be unlikely to confer susceptibility to schizophrenia.

PMID- 16086288
TI  - [Application of reverse transcription-multiplex nested PCR to detect MLL
      rearrangement in AML-M4/M5].
AB  - OBJECTIVE: To explore the value of reverse transcription-multiplex nested PCR in
      detecting MLL rearrangement in lzAML-M4/M5. METHODS: Bone marrow chromosome
      preparation was made using direct method or short-term culture. Karyotypic
      analysis was carried out by R-banding technique. Five common MLL fusion genes and
      MLL partial tandem duplication in 40 AML cases, including 12 M4 and 28 M5 were
      detected by reverse transcription(RT)-multiplex nested PCR. RESULTS: R-banding
      karyotypic analysis revealed 11q23 translocation including t(6;11)(q27;q23),
      t(9;11)(p21;q23), t(11;17)(q23;q21) and t(11;19)(q23;p13.1) in 7 cases. MLL
      rearrangements consisting of MLL/AF6 (1 case), MLL/AF9 (1 case), MLL/AF17 (2
      cases), MLL/ELL (2 cases) and MLL partial tandem duplication(2 cases) were
      detected in 8 cases by RT-multiplex nested PCR. Among 8 cases with MLL
      rearrangement, 6 were chromosome translocation, 2 were MLL partial tandem
      duplication. CONCLUSION: RT-multiplex nested PCR is a powerful technique in the
      detection of MLL rearrangement for tentativelly diagnosed AML-M4/M5.

PMID- 16086289
TI  - [Association of Xba I, Pvu II, and Bst U I polymorphisms of estrogen receptor
      alpha gene with bone mass in men].
AB  - OBJECTIVE: To investigate the association of polymorphism in estrogen receptor
      alpha (ER-alpha ) gene with bone mineral density(BMD) in men. METHODS: The ER
      alpha Xba I, Pvu II and Bst UI genotypes were determined by PCR-restriction
      fragment length polymorphism (RFLP) in 388 unrelated healthy men who were 46-80
      years old and were of Han nationalities in Shanghai city. Bone mineral densities
      (BMD, g/cm(2)) at lumbar spines 1-4 (L(1-4)) and at any sites of proximal femur,
      including femoral neck (Neck), trochanter (Troch) and Ward's triangle (Ward's)
      were measured by duel-energy X-ray absorptiometry. RESULTS: The frequencies
      distribution of Xba I and Pvu II alleles and genotypes in this cohort all
      followed the Hardy-Weinberg equilibrium. No Bst UI polymorphic site in ER-alpha
      gene was found in total samples. All subjects were of BB genotype. No significant
      association was found between Xba I genotype and BMD at any skeleton sites. The
      significant association was found between Pvu II genotype and BMD at L(1-4) and
      Ward's triangle site (P< 0.05). Compared against men with PP and pp genotype, men
      with Pp genotype had significantly higher mean BMD at L(1-4) and Ward's triangle
      site (P< 0.05). CONCLUSION: This study suggests that Bst UI polymorphism in ER
      alpha gene may be absent or rare in Chinese Han population. Pvu II polymorphism
      possibly influences the loss of trabecular bone mass in old men.

PMID- 16086290
TI  - [Analysis of 994(G--> T) mutation in the plasma platelet-activating factor
      acetylhydrolase gene in the patients with cerebral infarction].
AB  - OBJECTIVE: To investigate the relationship between plasma platelet-activating
      factor acetylhydrolase (PAF-AH) gene 994(G--> T) mutation in exon 9 and the
      patients with cerebral infarction in Chinese Hans. METHODS: The authors conducted
      a case-control study including 108 patients in three groups (atherosclerotic
      cerebral infarction group, lacunar infarction group and cerebral embolism group)
      and 215 normal subjects as controls. Genomic DNA was analyzed for the mutant
      allele by a specific polymerase chain reaction. RESULTS: The frequency of the
      mutant genotype in the 102 patients with cerebral infarction was 35.19%(32.41%
      heterozygotes and 2.78% homozygotes), and was 38.10%(34.92% heterozygotes and
      3.18% homozygotes) in the atherosclerotic cerebral infarction group, being all
      significantly higher than the control group's 20.46% (18.60% heterozygotes and
      1.86% homozygotes)(P< 0.01); however, the frequencies of the mutant genotype in
      the lacunar infarction group and cerebral embolism group were 32.35% (29.41%
      heterozygotes and 2.94% homozygotes) and 27.27% (27.27% heterozygotes and 0
      homozygotes) respectively, being not statistically different from those of the
      controls (P> 0.05). CONCLUSION: These findings show that the 994(G--> T) mutation
      of plasma PAF-AH gene may be an independent risk for atherosclerotic cerebral
      infarction, but not for lacunar infarction.

PMID- 16086291
TI  - [Study on the relationship between polymorphisms of peroxisome proliferators
      activated receptor-gamma coactivator-1alpha gene and type 2 diabetes in Shanghai
      Hans in China].
AB  - OBJECTIVE: To observe the association between single nucleotide polymorphism
      (SNP) of peroxisome proliferators-activated receptor-gamma coactivator-1alpha
      (PGC-1alpha ) gene and type 2 diabetes mellitus(T2DM). METHODS: Four common SNPs
      of PGC-1alpha gene were genotyped with polymerase chain reaction-restriction
      fragment length polymorphism(PCR-RFLP) and then analyzed with transmission
      disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 69
      T2DM pedigrees (310 individuals). Furthermore, the authors performed a case
      control study to genotype Gly482Ser in 156 patients with T2DM and 111 normal
      glucose tolerance people without family history. RESULTS: (1)There were no
      positive results in four variances in TDT-STDT analysis(P> 0.05). (2)The
      Gly482Ser exhibited a significant difference between the two groups. GA genotype
      carriers were at increased risk for T2DM (OR=1.85), and there was statistically
      significant difference in the allele frequency between the case and control
      groups(P=0.046). (3) The subjects with GG genotype at position Gly482Ser had a
      higher HDL-C and lower LDL-C and TG levels when compared against those with GA+AA
      genotype in the control group without family history(P=0.043,lzP=0.046, P=0.037
      respectively). CONCLUSION: This study suggested that the PGC-1alpha gene might be
      implicated in the pathogenesis of T2DM. But the studied SNPs in PGC-1alpha gene
      may not be major susceptibility ones of T2DM mellitus in Han people of Shanghai.

PMID- 16086292
TI  - [Nine polymorphisms of fibrinogen gene and their association with plasma
      fibrinogen levels in Hainan Han population].
AB  - OBJECTIVE: To investigate the allelic frequencies of polymorphisms of alpha Taq I
      and beta Bcl I, Hinf I A/C, 448 G/A, beta BsmA I G/C, +1689T/G, -148C/T, -249C/T,
      -455G/A in Hainan Han population and their association with plasma fibrinogen
      level. METHODS: Turbidmetric assay was used to measure plasma fibrinogen level of
      two hundred and thirty-eight healthy individuals. The genotypes were
      characterized by PCR-RFLP and sequence analysis. The relationships between the
      genotypes and plasma fibrinogen levels were analyzed by t test and ANOVA.
      RESULTS: The frequencies of the rare alleles of alpha Taq I and beta Bcl I, Hinf
      I A/C, 448 G/A, beta BsmA I G/C, +1689T/G, -148C/T, -249C/T, -455G/A
      polymorphisms were 0.445, 0.239, 0.134, 0.235, 0.273, 0.241, 0.265, 0.441, 0.254
      respectively. In the general population, the plasma fibrinogen level is
      significantly higher in the groups of genotypes -455GA and AA, -148CT and TT,
      alpha Taq I T1T1 than in the group of wild types(P=0.004, 0.015 and 0.043
      respectively). In the men, plasma fibrinogen level is significantly higher in the
      groups of genotypes -455GA and AA, -148CT and TT, alpha Taq I T1T1, alpha Taq I
      T1T2 than in the group of wild types(P=0.001, 0.023, 0.003 and 0.032
      respectively). In the women, no significant genotype association with plasma
      fibrinogen level was detected. CONCLUSION: There was linkage disequilibrium
      between the fibrinogen gene loci. The beta -455G/A beta 448G/A, alpha Fg Taq I
      polymorphisms were associated with the difference in plasma fibrinogen in men. A(
      455), T(-148) and alpha Taq I T1 alleles were associated with higher fibrinogen
      levels.

PMID- 16086293
TI  - [Polymorphism of apolipoprotein E gene and natural longevity in the Xinjiang
      Uighur people: an association study].
AB  - OBJECTIVE: To explore the distribution of polymorphisms of apolipoprotein E(apoE)
      gene and its relation to natural longevity in the Xinjiang Uighur people.
      METHODS: Using polymerase chain reaction-restriction fragment length
      polymorphism(PCR-RFLP), the authors obtained data from centenarians(n=42), 90
      year-old people (n=102), 65-70-year-old people (n=70) and controls(n=53).
      RESULTS: The frequencies of apoE genotypes epsilon 3/4, epsilon 3/3 and epsilon
      2/3 were 2.4%, 69.0% and 23.8% respectively in the centenarian group, and the
      frequencies of their epsilon 4, epsilon 3 and epsilon 2 alleles were 1.2%, 82.1%
      and 16.7%. The frequencies of genotype epsilon 3/4 and epsilon 4, epsilon 3
      allele in the centenarian group were significantly lower than those in
      controls(P< 0.01), whereas the frequencies of genotype epsilon 2/3 and epsilon 2
      allele in the centenarian group were significantly higher than those in
      controls(P< 0.01). Longevity was noted to be positively correlated with epsilon 2
      and negatively correlated with epsilon 4. CONCLUSION: This relationship reflects
      a genetic influence on differential survival and may point to pleiotropic age
      dependent effects on longevity.

PMID- 16086294
TI  - [Analysis on HLA haplotypes of loci HLA-A, -B, and -DRB1 in northwest Chinese Han
      population].
AB  - OBJECTIVE: To investigate HLA-A, -B and -DRB1 allele and HLA-A-B, B-DRB1, A-B
      DRB1 haplotype frequencies in the northwest Chinese Han population. METHODS: The
      authors investigated the HLA-A, -B, -DRB1 allele and haplotype in a northwest
      Chinese Han population based on 62 families and 101 individuals by use of PCR
      sequence specific oligonucleotide probes(PCR-SSOP) DNA typing methods. RESULTS:
      Fifteen alleles for the locus HLA-A, 28 alleles for the HLA-B locus and 13
      alleles for the HLA-DRB1 were detected. The results showed that the most frequent
      HLA alleles found were A02 (0.3244), B13 (0.1200), and DRB1*15 (0.1400). Allele
      frequencies of more than 10% for HLA antigens were A02, A11, A24, B13, B15, B40,
      DRB1*04, DRB1*07, DRB1*09, DRB1*15. In the analysis of HLA haplotypes, 122 kinds
      of HLA-A-B haplotypes and 147 kinds HLA-B-DRB1 haplotypes were found. Two hundred
      and seventy-eight kinds of HLA-A-B-DRB1 haplotypes were found, comprising
      61.78%(278/450) of total theoretical haplotypes. Eighty-three kinds of HLA-A-B
      DRB1 haplotypes were shown to have at least two same haplotypes, comprising
      18.44%(83/450) of total theoretical haplotypes. The most common HLA-A-B-DRB1
      haplotypes were A30-B13-DRB1*07, A02-B46-DRB1*09, A01-B37-DRB1*10, A24-B15
      DRB1*15, A02-B46-DRB1*08, A33-B58-DRB1*03. CONCLUSION: The data can be used for
      the estimation of the probability of finding haplotypically identical, related or
      unrelated bone marrow donor for an individual patient, and forensic and paternity
      tests to estimate the frequency of a DNA profile or anthropologic research.

PMID- 16086295
TI  - [HLA class I and II polymorphism and haplotypes in Guangdong Han population].
AB  - OBJECTIVE: To analyze the polymorphism and haplotypes of HLA class I and II in
      Guangdong Han population and detect the HLA-A, B, Cw and DRB1 allele frequencies.
      METHODS: An auto semi-quantitative PCR-sequence speacific oligonucleotide
      probe(PCR-SSOP) method was adopted in exploring the HLA-A, B, Cw and DRB1
      genotypes of the samples from 160 bone marrow donors. RESULTS: Twelve HLA-A, 23
      B, 11 Cw and 13 DRB1 alleles were obtained. A total of 9 HLA-A-B, 20 Cw-B, 7 A
      Cw, and 8 A-DRB1, 9 B-DRB1, 10 Cw-DRB1 haplotypes were found. CONCLUSION: HLA
      class I and II alleles in Guangdong Han population have plenty of polymorphisms.
      The haplotype distribution possesses territory characteristic.

PMID- 16086296
TI  - [Distribution of genotype and allele frequencies of dopamine D4 receptor gene 48
      bp variable number tandem repeat polymorphism in Chinese Han population in
      Hunan].
AB  - OBJECTIVE: To investigate the distribution of genotype and allele frequencies of
      the dopamine D4 receptor(DRD4) gene exon 3 48 bp variable number of tandem
      repeats polymorphism in Hunan Han population. METHODS: The genotype and alleles
      of 304 healthy persons were examined with polymerase chain reaction, denaturing
      polyacrylamide gel electrophoresis and silver staining. RESULTS: Seven alleles
      and twelve genotypes were found. The most common allele was allele 5 with a
      frequency of 70.6%. There was statistically significant difference in allele
      distribution between the Hunan Han population and the Han population of other
      regions such as Shanghai, Beijing and Sichuan in China (P< 0.05). Different
      allele frequency distributions were observed when compared to other ethnic
      populations such as Japanese, American, Mexican, and Italian (P< 0.05).
      CONCLUSION: The distributions of allele of DRD4 gene exhibit regional and ethnic
      heterogeneity.

PMID- 16086297
TI  - [Genetic polymorphism of D6S477, D9S1118, D18S865, D19S400, and D20S161 short
      tandem repeat loci in Qingdao Han population].
AB  - OBJECTIVE: To illuminate the preliminary genotype and allele frequency
      distribution of D6S477 and the other four short tandem repeat(STR) loci in
      Chinese Han population in Qingdao area and to probe the possibility of their
      genetic application. METHODS: Two hundred ACD-blood specimens were collected from
      the unrelated individuals in Qingdao. The DNA samples were extracted with Chelex
      method and were amplified by polymerase chain reaction technique. The PCR
      products were analyzed by polyacrylamide gel electrophoresis and displayed using
      silver staining. RESULTS: The authors obtained the allele frequency distribution
      and preliminary genotype of D6S477, D9S1118, D18S865, D19S400 and D20S161 STR
      loci. No deviation from Hardy-Weinberg equilibrium was observed in the five loci.
      CONCLUSION: All the five loci have higher chance of exclusion and discriminating
      power, and they will be useful markers for researches in genetics.

PMID- 16086298
TI  - Fast spin-echo for multiple mouse magnetic resonance phenotyping.
AB  - High-resolution magnetic resonance imaging is emerging as a powerful tool for
      phenotyping mice in biologic studies of genetic expression, development, and
      disease progression. In several applications, notably random mutagenesis trials,
      large cohorts of mice must be examined for abnormalities that may occur in any
      part of the body. In the aim of establishing a protocol for imaging multiple mice
      simultaneously in a standardized high-throughput fashion, this study investigates
      variations of a three-dimensional fast spin-echo sequence that implements driven
      equilibrium, modified refocusing, and partial excitation pulses. Sequence
      variations are compared by simulated and experimental measurements in phantoms
      and mice. Results indicate that when using a short repetition time (TR<or=T1) a
      sequence employing a partial excitation tip angle provides both improved signal
      and good T2 contrast compared with standard fast spin-echo imaging. This sequence
      is used to simultaneously acquire four live mouse head images at 100 microm
      isotropic resolution with a scan time under 3 h at 7 T.

PMID- 16086299
TI  - Magnetic resonance imaging assessment of myocardial elastic modulus and viscosity
      using displacement imaging and phase-contrast velocity mapping.
AB  - Approximately half of patients experiencing congestive heart failure present with
      a normal left ventricular ejection fraction. Perturbations in material properties
      affecting ventricular pressure/volume relationships likely play an important role
      in the "stiff heart syndrome" yet noninvasive tools permitting the accurate
      assessment of myocardial elasticity are extremely limited. We developed an MRI
      based technique to examine regional left ventricular stress/strain relationships
      by incorporating displacement-encoding with stimulated-echoes (DENSE) and phase
      contrast (PC) velocity mapping and compared regional elastic moduli (EM) and
      viscous delay time constants (VDTCs) (N=10) with immediate postmortem direct
      strain gauge measurements (N=8) and global chamber compliance (literature) in
      normal dogs. EMs by MRI were significantly greater in papillary muscle columns
      when compared with lateral wall and septal locations by MRI (7.59+/-1.65 versus
      3.40+/-0.87 versus 2.55+/-0.93 kPa, P<0.0001) and were in agreement with direct
      strain gauge measurements (3.78+/-0.93 and 2.96+/-0.88 kPa for the lateral wall
      and the septum, P=ns for both versus MRI). MRI-determined VDTCs were similar in
      the three regions (VDTC=-1.15+/-12.37 versus 3.04+/-7.25 versus 4.17+/-5.76 ms,
      P=ns) and did not differ from lateral and septal wall strain gauge assessment
      (VDTC=3.09+/-0.40 and 4.57+/-1.86 ms, P=ns for both versus MRI). Viscoelastic
      measurements obtained in six normal volunteers demonstrated the feasibility of
      this technique in humans. Noninvasive, regional assessment of myocardial
      stiffness using DENSE and PC velocity mapping techniques is accurate in a canine
      model and feasible in humans.

PMID- 16086300
TI  - Simultaneous spin-echo refocusing.
AB  - A new approach to spin-echo imaging is presented in which the 180 degrees RF
      pulse refocuses two or more spin-echoes at different positions in the readout
      period. When simultaneous echo refocusing (SER) is implemented using multiple 180
      degrees pulses, an undesirable mixing of stimulated echoes and primary echoes
      from different slices can occur. A novel periodic gradient spoiler scheme
      eliminates this potential source of artifacts without spoiling the correctly
      timed stimulated echoes, which, similar to RARE (TSE) sequences, add coherently
      to the primary echoes. Comparisons show equivalent artifact elimination using
      phase cycling, periodic spoiling, and a previously developed spoiling scheme for
      non-Carr-Purcell-Meiboom-Gill sequences. A comparison of head images at 1.5 T
      acquired with SER-TSE and conventional TSE T1-weighted sequences show no
      degradation in image quality nor SNR. T2-weighted imaging is not achievable with
      the current implementation, but possible solutions are proposed. The proposed
      technique might prove especially beneficial at higher field strengths, where the
      reduced number of refocusing pulses for multislice SER-TSE decreases RF power
      deposition. SER spin-echo imaging offers an approach that is very different from
      low flip angle imaging to mitigate RF heating limitations in high-field clinical
      imaging.

PMID- 16086301
TI  - Simultaneous water and lipid suppression for in vivo brain spectroscopy in
      humans.
AB  - A method to achieve simultaneous water and lipid suppression is described. The
      key feature of the new dual suppression technique is the use of the well-known
      hyperbolic secant (HS) waveform as a 90 degrees saturation pulse. Two HS pulses
      with opposite frequency offsets are employed either sequentially or
      simultaneously to saturate resonance frequencies corresponding to water and
      lipid, while leaving the target spins untouched. The excitation bandwidth is
      controlled by the frequency sweep and offset of each pulse, while varying the
      pulse length controls the transition bandwidth. An example of the use of the dual
      saturation method in in vivo magnetic resonance spectroscopic imaging of the
      human brain is presented.

PMID- 16086302
TI  - Whole-body magnetic resonance imaging featuring moving table continuous data
      acquisition with high-precision position feedback.
AB  - A novel setup for whole-body MR imaging with moving table continuous data
      acquisition has been developed and evaluated. The setup features a manually
      positioned moving table platform with integrated phased-array surface
      radiofrequency coils. A high-precision laser position sensor was integrated into
      the system to provide real-time positional data that were used to compensate for
      nonlinear manual table translation. This setup enables continuous 2D and 3D whole
      body data acquisition during table movement with surface coil image quality. The
      concept has been successfully evaluated with whole-body steady-state free
      precession (TrueFISP) anatomic imaging in five healthy volunteers. Seamless
      coronal and sagittal slices of continually acquired whole-body data during table
      movement were accurately reconstructed. The proposed strategy is potentially
      useful for a variety of applications, including whole-body metastasis screening,
      whole-body MR angiography, large field-of-view imaging in short bore systems, and
      for moving table applications during MR-guided interventions.

PMID- 16086303
TI  - Hemispherical gradient coils for magnetic resonance imaging.
AB  - Hemispherical gradient coils offer an open geometry that is well suited to
      imaging of the human brain. The windings of a hemispherical gradient coil are on
      average closer to the target region than those of a comparable cylindrical coil,
      and consequently hemispherical coils can produce higher efficiency at fixed
      inductance. The mathematical formalism needed for the design of hemispherical
      gradient coils is described here, including expressions relating the current
      distribution on the hemisphere to the magnetic field generated, as well as the
      stored energy and power dissipation. In addition, expressions for the torque
      experienced by the current distribution in the presence of the main magnetic
      field have been derived and used to develop an approach allowing the design of
      torque-balanced, hemispherical transverse gradient coils. Hemispherical coil
      designs suitable for brain imaging are presented and shown to have improved
      performance compared with their cylindrical counterparts. Small, prototype,
      hemispherical z- and x-gradient coils have been constructed and tested in phase
      mapping experiments at 3 T. The experimental results show good agreement with
      theoretical predictions, validating the mathematical expressions used in the coil
      design process. The formalism also allows the design of coils wound on a complete
      spherical surface, and the performance of such coils is additionally described
      here.

PMID- 16086304
TI  - Recovery of phase inconsistencies in continuously moving table extended field of
      view magnetic resonance imaging acquisitions.
AB  - MR images formed using extended FOV continuously moving table data acquisition
      can have signal falloff and loss of lateral spatial resolution at localized,
      periodic positions along the direction of table motion. In this work we identify
      the origin of these artifacts and provide a means for correction. The artifacts
      are due to a mismatch of the phase of signals acquired from contiguous sampling
      fields of view and are most pronounced when the central k-space views are being
      sampled. Correction can be performed using the phase information from a
      periodically sampled central view to adjust the phase of all other views of that
      view cycle, making the net phase uniform across each axial plane. Results from
      experimental phantom and contrast-enhanced peripheral MRA studies show that the
      correction technique substantially eliminates the artifact for a variety of phase
      encode orders.

PMID- 16086305
TI  - NMR measurements of gaseous sulfur hexafluoride (SF6) to probe the cross-linking
      of EPDM rubber.
AB  - The effects of embedding gaseous SF6 into EPDM rubber were investigated using NMR
      methods. It was found that observed sorption and desorption processes follow the
      behavior of the dual mode sorption model. A strong correlation was found between
      EPDM cross-linking and transversal relaxation time of embedded SF6. EPDM samples
      with different cross-link densities, preliminarily determined by 1H transversal
      relaxation using the Gotlib model and Litvinov's method, were investigated using
      embedded SF6. The sensitivity of the 19F transversal relaxation rate of SF6 to
      the EPDM cross-link density variation was found to be at least 10 times higher
      than for 1H in the polymer chain. First experiments on probing the swelling
      effects in EPDM due to its contact with polar liquids have been performed.

PMID- 16086306
TI  - Fetal oxygen tension promotes tenascin-C-dependent lung branching morphogenesis.
AB  - Tenascin-C (TN-C) is a mesenchyme-derived extracellular matrix (ECM) glycoprotein
      required for fetal lung branching morphogenesis. Given that the low oxygen (O(2))
      environment of the fetus is also essential for normal lung branching
      morphogenesis, we determined whether fetal O(2) tension supports this process by
      promoting TN-C expression. Initial studies showed that 15-day fetal rat lung
      explants cultured for 2 days at 3% O(2) not only branched well, but they also
      expressed higher levels of TN-C when compared to lungs maintained at 21% O(2),
      which branched poorly. Antisense oligonucleotide studies demonstrated that TN-C
      produced in response to 3% O(2) was essential for lung branching morphogenesis.
      As well, exogenous TN-C protein was shown to promote branching of lung epithelial
      rudiments cultured at 21% O(2). Because ECM-degrading proteinases are capable of
      catabolizing TN-C protein, we reasoned that 3% O(2) might promote TN-C deposition
      by limiting the activity of these enzymes within the fetal lung. Consistent with
      this idea, gelatin zymography showed that the activity of a 72-kDa gelatinase,
      identified as matrix metalloproteinase-2 (MMP-2), was lower at 3% O(2) vs. 21%
      O(2). Furthermore, pharmacologic inhibition of MMP-2 activity in fetal lung
      explants cultured at 21% O(2) resulted in increased TN-C deposition within the
      mesenchyme, as well as enhanced branching morphogenesis. Collectively, these
      studies indicate that fetal O(2) tension promotes TN-C-dependent lung epithelial
      branching morphogenesis by limiting the proteolytic turnover of this ECM
      component within the adjacent mesenchyme.

PMID- 16086307
TI  - Full-brain T1 mapping through inversion recovery fast spin echo imaging with time
      efficient slice ordering.
AB  - Brain T1 mapping has important clinical applications in detecting brain
      disorders. Conventional T1 mapping techniques are usually based on inversion
      recovery spin echo (IRSE) imaging or its more time-efficient counterpart
      inversion recovery fast spin echo (IRFSE) imaging because they can deliver good
      image quality. Multiple inversion times are required to accurately estimate T1
      over a wide range of values. Without acquisition optimization, both the IRSE and
      the IRFSE T1 mapping techniques require long scan times to image the whole brain.
      To reduce the scan time and maintain the quality of the T1 maps, we propose a new
      full-brain T1 mapping pulse sequence based on a multislice inversion recovery
      fast spin echo imaging using a time-efficient slice ordering technique.

PMID- 16086308
TI  - Factor XI deficiency database: an interactive web database of mutations,
      phenotypes, and structural analysis tools.
AB  - Factor XI (FXI) is the zymogen of a serine protease enzyme in the intrinsic
      pathway of blood coagulation and is an important factor in the creation of a
      stable fibrin clot. Deficiency of FXI leads to an injury-related bleeding
      disorder and is remarkable for the lack of correlation between bleeding symptoms
      and FXI coagulant activity (FXI:C). The FXI protein is composed of five domains:
      four tandem repeat domains of approximately 80 residues known as Apple (Ap)
      domains, and the catalytic serine protease (Sp) domain. A total of 65 mutations
      throughout the FXI gene (F11) have been reported in FXI deficient patients. An
      interactive web database of these mutations has been created (www.FactorXI.org)
      that integrates the phenotypic data with genetic data and structural homology
      models for the five FXI domains. The database provides a central repository for
      all reported genetic alterations within F11. With the use of recently developed
      visualization tools, each mutation can be highlighted on the structural models of
      the FXI domains together with an appropriate survey of patient data, such as
      FXI:C levels and FXI antigen levels. The database also enables new F11 mutations
      to be interpreted. The interactive design of this database will lead to a more
      comprehensive comparative understanding of the genetic factors that influence
      bleeding risk.

PMID- 16086309
TI  - Worldwide haplotype diversity and coding sequence variation at human bitter taste
      receptor loci.
AB  - Bitter taste perception in humans is mediated by receptors encoded by 25 genes
      that together comprise the TAS2R (or T2R) gene family. The ability to identify
      the ligand(s) for each of these receptors is dependent on understanding allelic
      variation in TAS2R genes, which may have a significant effect on ligand
      recognition. To investigate the extent of coding variation among TAS2R alleles,
      we performed a comprehensive evaluation of sequence and haplotype variation in
      the human bitter taste receptor gene repertoire. We found that these genes
      exhibit substantial coding sequence diversity. In a worldwide population sample
      of 55 individuals, we found an average of 4.2 variant amino acid positions per
      gene. In aggregate, the 24 genes analyzed here, along with the
      phenylthiocarbamide (PTC) receptor gene analyzed previously, specify 151
      different protein coding haplotypes. Analyses of the ratio of synonymous and
      nonsynonymous nucleotide substitutions using the Ka/Ks ratio revealed an excess
      of amino acid substitutions relative to most other genes examined to date (Ka/Ks
      = 0.94). In addition, comparisons with more than 1,500 other genes revealed that
      levels of diversity in the TAS2R genes were significantly greater than expected
      (pi = 0.11%; p < 0.01), as were levels of differentiation among continental
      populations (FST = 0.22; p < 0.05). These diversity patterns indicate that
      unusually high levels of allelic variation are found within TAS2R loci and that
      human populations differ appreciably with respect to TAS2R allele frequencies.
      Diversity in the TAS2R genes may be accounted for by natural selection, which may
      have favored alleles responsive to toxic, bitter compounds found in plants. These
      findings are consistent with the view that different alleles of the TAS2R genes
      encode receptors that recognize different ligands, and suggest that the
      haplotypes we have identified will be important in studies of receptor-ligand
      recognition.

PMID- 16086310
TI  - Dynamics and unexpected localization of the plakin binding protein, kazrin, in
      mouse eggs and early embryos.
AB  - The cell uses the cytoskeleton in virtually every aspect of cell survival and
      function. One primary function of the cytoskeleton is to connect to and stabilize
      intercellular junctions. To accomplish this task, microtubules, actin filaments,
      and intermediate filaments utilize cytolinker proteins, which physically bind the
      cytoskeletal filament to the core proteins of the adhesion junction. The plakin
      family of linker proteins have been in the spotlight recently as critical
      components for embryo survival and, when mutated, the cause of diseases such as
      muscular dystrophy and cardiomyopathies. Here, we reveal the dynamics of a
      recently discovered plakin binding protein, kazrin (kaz), during early mouse
      development. Kaz was originally found in adult tissues, primarily epidermis,
      linking periplakin to the plasma membrane and colocalizing with desmoplakin in
      desmosomes. Using reverse transcriptase-polymerase chain reaction, Western blots,
      and confocal microscopy, we found kaz in unfertilized eggs associated with the
      spindle apparatus and cytoskeletal sheets. As quickly as 5 min after egg
      activation, kaz relocates to a diffuse peri-spindle position, followed 20-30 min
      later by clear localization to the presumptive cytokinetic ring. Before the
      blastocyst stage of development, kaz associates with the nuclear matrix in a cell
      cycle-dependent manner, and also associates with the cytoplasmic actin
      cytoskeleton. After blastocyst formation, kaz localization and potential
      function(s) become highly complex as it is found associating with cell-cell
      junctions, the cytoskeleton, and nucleus. Postimplantation stages of development
      reveal that kaz retains a multifunctional, tissue-specific role as it is detected
      at diverse locations in various embryonic tissue types.

PMID- 16086311
TI  - Homodyne reconstruction and IDEAL water-fat decomposition.
AB  - Multipoint water-fat separation methods have received renewed interest because
      they provide uniform separation of water and fat despite the presence of B0 and
      B1 field inhomogeneities. Unfortunately, full-resolution reconstruction of
      partial k-space acquisitions has been incompatible with these methods.
      Conventional homodyne reconstruction and related algorithms are commonly used to
      reconstruct partial k-space data sets by exploiting the Hermitian symmetry of k
      space in order to maximize the spatial resolution of the image. In doing so,
      however, all phase information of the image is lost. The phase information of
      complex source images used in a water-fat separation acquisition is necessary to
      decompose water from fat. In this work, homodyne imaging is combined with the
      IDEAL (iterative decomposition of water and fat with echo asymmetry and least
      squares estimation) method to reconstruct full resolution water and fat images
      free of blurring. This method is extended to multicoil steady-state free
      precession and fast spin-echo applications and examples are shown.

PMID- 16086312
TI  - Microdeletions and microinsertions causing human genetic disease: common
      mechanisms of mutagenesis and the role of local DNA sequence complexity.
AB  - In the Human Gene Mutation Database (www.hgmd.org), microdeletions and
      microinsertions causing inherited disease (both defined as involving < or = 20 bp
      of DNA) account for 8,399 (17%) and 3,345 (7%) logged mutations, in 940 and 668
      genes, respectively. A positive correlation was noted between the microdeletion
      and microinsertion frequencies for 564 genes for which both microdeletions and
      microinsertions are reported in HGMD, consistent with the view that the
      propensity of a given gene/sequence to undergo microdeletion is related to its
      propensity to undergo microinsertion. While microdeletions and microinsertions of
      1 bp constitute respectively 48% and 66% of the corresponding totals, the
      relative frequency of the remaining lesions correlates negatively with the length
      of the DNA sequence deleted or inserted. Many of the microdeletions and
      microinsertions of more than 1 bp are potentially explicable in terms of slippage
      mutagenesis, involving the addition or removal of one copy of a mono-, di-, or
      trinucleotide tandem repeat. The frequency of in-frame 3-bp and 6-bp
      microinsertions and microdeletions was, however, found to be significantly lower
      than that of mutations of other lengths, suggesting that some of these in-frame
      lesions may not have come to clinical attention. Various sequence motifs were
      found to be over-represented in the vicinity of both microinsertions and
      microdeletions, including the heptanucleotide CCCCCTG that shares homology with
      the complement of the 8-bp human minisatellite conserved sequence/chi-like
      element (GCWGGWGG). The previously reported indel hotspot GTAAGT and its
      complement ACTTAC were also found to be overrepresented in the vicinity of both
      microinsertions and microdeletions, thereby providing a first example of a
      mutational hotspot that is common to different types of gene lesion. Other motifs
      overrepresented in the vicinity of microdeletions and microinsertions included
      DNA polymerase pause sites and topoisomerase cleavage sites. Several novel
      microdeletion/microinsertion hotspots were noted and some of these exhibited
      sufficient similarity to one another to justify terming them "super-hotspot"
      motifs. Analysis of sequence complexity also demonstrated that a combination of
      slipped mispairing mediated by direct repeats, and secondary structure formation
      promoted by symmetric elements, can account for the majority of microdeletions
      and microinsertions. Thus, microinsertions and microdeletions exhibit strong
      similarities in terms of the characteristics of their flanking DNA sequences,
      implying that they are generated by very similar underlying mechanisms.

PMID- 16086313
TI  - Strong bias in the location of functional promoter polymorphisms.
AB  - A considerable proportion of heritable human phenotypic variation is thought to
      result from altered gene expression. Unfortunately, it is currently impossible to
      use bioinformatic analysis to discriminate between DNA sequence variants that are
      likely to influence gene expression and those that are not. In an attempt to
      define some of the characteristics of promoter polymorphisms with functional
      effects on gene expression, we examined 674 haplotypes representing 247 unique
      gene promoters using a standardized reporter gene assay system. Sequence variants
      that altered gene expression by 1.5-fold or more were strongly biased toward a
      location in the core and proximal promoter regions, 50% being within the first
      100 bases 5' to the transcription start site. No bias was seen in the allele
      frequencies of functional and nonfunctional sequence variants. Only 33% of the
      functional variants were found in known consensus transcription factor binding
      sequences or motifs, which suggests that either there are many unknown
      transcription factor binding motifs or other, unknown mechanisms are involved.
      The genes with functional polymorphisms that are reported here for the first time
      include AGTRL2, CAT, CHRNA5, CTSG, CYP2D6, DLD, ERCC1, GABRA1, GABRP, HNRPH3,
      HIP1, IGKV1-9, KCNJ15, KCNK6, KLK1, MSMB, MYOC, NPY2R, NOTCH4, ORM2, PEDF,
      PTPRCAP, ST16 (IL24), SULT1A1, and TSHR.

PMID- 16086314
TI  - Continuous ASL (CASL) perfusion MRI with an array coil and parallel imaging at
      3T.
AB  - The purpose of this work was to assess the feasibility and efficacy of using an
      array coil and parallel imaging in continuous arterial spin labeling (CASL)
      perfusion MRI. An 8-channel receive-only array head coil was used in conjunction
      with a surrounding detunable volume transmit coil. The signal to noise ratio
      (SNR), temporal stability, cerebral blood flow (CBF), and perfusion image
      coverage were measured from steady state CASL scans using: a standard volume
      coil, array coil, and array coil with 2- and 3-fold accelerated parallel imaging.
      Compared to the standard volume coil, the array coil provided 3 times the average
      SNR increase and higher temporal stability for the perfusion weighted images,
      even with threefold acceleration. Although perfusion images of the array coil
      were affected by the inhomogeneous coil sensitivities, this effect was invisible
      in the quantitative CBF images, which showed highly reproducible perfusion values
      compared to the standard volume coil. The unfolding distortions of parallel
      imaging were suppressed in the perfusion images by pairwise subtraction, though
      they sharply degraded the raw EPI images. Moreover, parallel imaging provided the
      potential of acquiring more slices due to the shortened acquisition time and
      improved coverage in brain regions with high static field inhomogeneity. Such
      results highlight the potential utility of array coils and parallel imaging in
      ASL perfusion MRI.

PMID- 16086315
TI  - Scanning of genetic effects of alcohol metabolism gene (ADH1B and ADH1C)
      polymorphisms on the risk of alcoholism.
AB  - Alcoholism is a multifactorial and polygenic disorder involving complex gene-to
      gene and gene-to-environment interactions. Alcohol metabolism is one of the
      biological determinants that could significantly be influenced by genetic
      polymorphisms in alcohol-metabolism genes. These genetic polymorphisms are
      believed to influence drinking behavior and development of alcoholism. Direct DNA
      sequencing of whole ADH1B and ADH1C genes revealed 36 sequence variants,
      including six nonsynonymous and 14 novel polymorphisms. Seventeen polymorphisms
      among them were selected for genotyping in a larger study (n = 352) based on
      linkage disequilibria (LDs) among SNPs, locations, and frequencies. Hardy
      Weinberg equilibrium (HWE) analyses of polymorphisms revealed severe deviations
      only in alcoholics, which strongly suggest that a selection bias (or pressure)
      may be involved. The analyses of genotype distribution in alcoholics (n = 106)
      and normal controls (n = 246) showed dramatic associations with the risk of
      alcoholism. Fourteen polymorphisms in ADH1C and ADH1B showed a series of
      different strengths of association and magnitudes of risk. Based on referent and
      subgroup analysis, it was strongly suggested that the genetic effects come from
      the ADH1B*47Arg/*47Arg genotype, and that the positive signals from other sites
      are just tracking the genetic effect of ADH1B His47Arg. In this article we
      present summaries of previous studies and of the present study, to give an
      overview of the worldwide effects of ADH1B His47Arg on the risk of alcoholism.
      The information derived from this study could be valuable for understanding the
      genetic factors involved in the risk of alcoholism and facilitate further
      investigation in other ethnic groups.

PMID- 16086316
TI  - Achieving sufficient spectral bandwidth for volumetric 1H echo-planar
      spectroscopic imaging at 4 Tesla.
AB  - Complete coverage of the in vivo proton metabolite spectrum, including downfield
      resonances, requires a spectral bandwidth of approximately 9 ppm. Spectral
      bandwidth of in vivo echo-planar spectroscopic imaging (EPSI) is primarily
      limited by gradient strength of the oscillating readout gradient, gradient slew
      rate, and limits on peripheral nerve stimulation for human subjects. Furthermore,
      conventional EPSI reconstruction, which utilizes even and odd readout echoes
      separately, makes use of only half the spectral bandwidth. In order to regain
      full spectral bandwidth in EPSI, it has previously been suggested to apply an
      interlaced Fourier transform (iFT), which uses even and odd echoes
      simultaneously. However, this method has not been thoroughly analyzed regarding
      its usefulness for in vivo 3D EPSI. In this Note, limitations of the iFT method
      are discussed and an alternative, cyclic spectral unwrapping, is proposed, which
      is based on prior knowledge of typical in vivo spectral patterns.

PMID- 16086317
TI  - Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations
      in ABCC6.
AB  - Pseudoxanthoma elasticum (PXE) is a systemic heritable disorder that affects the
      elastic tissue in the skin, eye, and cardiovascular system. Mutations in the
      ABCC6 gene cause PXE. We performed a mutation screen in ABCC6 using haplotype
      analysis in conjunction with direct sequencing to achieve a mutation detection
      rate of 97%. This screen consisted of 170 PXE chromosomes in 81 families, and
      detected 59 distinct mutations (32 missense, eight nonsense, and six likely
      splice-site point mutations; one small insertion; and seven small and five large
      deletions). Forty-three of these mutations are novel variants, which increases
      the total number of PXE mutations to 121. While most mutations are rare, three
      nonsense mutations, a splice donor site mutation, and the large deletion
      comprising exons 23-29 (c.2996_4208del) were identified as relatively frequent
      PXE mutations at 26%, 5%, 3.5%, 3%, and 11%, respectively. Chromosomal
      haplotyping with two proximal and two distal polymorphic markers flanking ABCC6
      demonstrated that most chromosomes that carry these relatively frequent PXE
      mutations have related haplotypes specific for these mutations, which suggests
      that these chromosomes originate from single founder mutations. The types of
      mutations found support loss-of-function as the molecular mechanism for the PXE
      phenotype. In 76 of the 81 families, the affected individuals were either
      homozygous for the same mutation or compound heterozygous for two mutations. In
      the remaining five families with one uncovered mutation, affected showed allelic
      compound heterozygosity for the cosegregating PXE haplotype. This demonstrates
      pseudo-dominance as the relevant inheritance mechanism, since disease
      transmission to the next generation always requires one mutant allelic variant
      from each parent. In contrast to other previous clinical and molecular claims,
      our results show evidence only for recessive PXE. This has profound consequences
      for the genetic counseling of families with PXE.

PMID- 16086318
TI  - Spectrum of molecular defects and mutation detection rate in patients with severe
      hemophilia A.
AB  - Hemophilia A is the most frequently occurring X-linked bleeding disorder,
      affecting one to two out of 10,000 males worldwide. Various types of mutations in
      the F8 gene are causative for this condition. It is well known that the most
      common mutation in severely affected patients is the intron 22 inversion, which
      accounts for about 45% of cases with F8 residual activity of less than 1%.
      Therefore, the aim of the present study was to determine the spectrum and
      distribution of mutations in the F8 gene in a large group of patients with severe
      hemophilia A who previously tested negative for the common intron 22 inversion.
      Here we report on a mutation analysis of 86 patients collected under the above
      mentioned criterion. The pathogenic molecular defect was identified in all
      patients, and thus our detection rate was virtually 100%. Thirty-four of the
      identified mutations are described for the first time. The newly detected amino
      acid substitutions were scored for potential gross or local conformational
      changes and influence on molecular stability for every single F8 domain with
      available structures, using homology modeling.

PMID- 16086319
TI  - T1, T2 relaxation and magnetization transfer in tissue at 3T.
AB  - T1, T2, and magnetization transfer (MT) measurements were performed in vitro at 3
      T and 37 degrees C on a variety of tissues: mouse liver, muscle, and heart; rat
      spinal cord and kidney; bovine optic nerve, cartilage, and white and gray matter;
      and human blood. The MR parameters were compared to those at 1.5 T. As expected,
      the T2 relaxation time constants and quantitative MT parameters (MT exchange
      rate, R, macromolecular pool fraction, M0B, and macromolecular T2 relaxation
      time, T2B) at 3 T were similar to those at 1.5 T. The T1 relaxation time values,
      however, for all measured tissues increased significantly with field strength.
      Consequently, the phenomenological MT parameter, magnetization transfer ratio,
      MTR, was lower by approximately 2 to 10%. Collectively, these results provide a
      useful reference for optimization of pulse sequence parameters for MRI at 3 T.

PMID- 16086320
TI  - Cell death during germ band inversion, dorsal closure, and nervous system
      development in the spider Cupiennius salei.
AB  - Cell death is an important feature in the development of animals, because it is
      one possibility for the embryo to control cell number in developing tissues and
      thereby determine the form of a growing organ. In Drosophila, cell death has been
      shown to be involved in the shaping of many different organs of the embryo. We
      have used terminal deoxynucleotidyl transferase-mediated dUTP-digoxygenin nick
      end labeling (TUNEL) and an antibody against the activated form of caspase-3 to
      visualize cell death in the spider Cupiennius salei. We find that similar to
      Drosophila, massive cell death occurs during the development of the nervous
      system, suggesting that this is an ancestral feature in the arthropods. We also
      detect cell death during leg development, most probably related to the formation
      of tarsal sensory organs. No cell death seems to be required for germ band
      segmentation. Most importantly, we find that cell death has a role in germ band
      inversion, a morphogenetic event unique to spiders that involves epithelial
      fission ventrally and tissue fusion dorsally. Our data show that germ band
      inversion involves cell death to facilitate the ventral splitting of the germ
      band, as well as the epithelial fusion during dorsal closure.

PMID- 16086321
TI  - Processing of radial fast spin-echo data for obtaining T2 estimates from a single
      k-space data set.
AB  - Radially acquired fast spin-echo data can be processed to obtain T2-weighted
      images and a T2 map from a single k-space data set. The general approach is to
      use data at a specific TE (or narrow TE range) in the center of k-space and data
      at other TE values in the outer part of k-space. With this method high-resolution
      T2-weighted images and T2 maps are obtained in a time efficient manner. The
      mixing of TE data, however, introduces errors in the T2-weighted images and T2
      maps that affect the accuracy of the T2 estimates. In this work, various k-space
      data processing methods for reconstructing T2-weighted images and T2 maps from a
      single radial fast spin-echo k-space data set are analyzed in terms of the
      accuracy of T2 estimates. The analysis is focused on the effect of image
      artifacts, object dependency, and noise on the T2 estimates. Results are
      presented in computer-generated phantoms and in vivo.

PMID- 16086322
TI  - The 5' region of the MSH2 gene involved in hereditary non-polyposis colorectal
      cancer contains a high density of recombinogenic sequences.
AB  - MSH2 rearrangements are involved in approximately 10% of hereditary non-polyposis
      colorectal cancer (HNPCC) families, and in most of the rearrangements, exon 1 is
      deleted. We scanned by quantitative multiplex polymerase chain reaction (PCR) of
      short fluorescent fragments (QMPSF) 200 kb of genomic sequences upstream of the
      MSH2 transcription initiation site in 21 HNPCC families with exon 1 deletions.
      This QMPSF scan revealed 12 distinct 5' breakpoints located up to 200 kb upstream
      of the MSH2 transcription initiation site. Sequencing analysis of the rearranged
      allele in 17 families revealed that most of the deletions (15/17) resulted from
      homologous Alu-mediated recombination. QMPSF and sequencing analysis in these 21
      families led us to detect the presence of 20 distinct 5' breakpoints. In 14 out
      of 15 Alu-mediated recombinations, we found, either within the identical region
      in which the recombination had probably occurred or in its vicinity, the 26-bp
      Alu core sequence containing the recombinogenic Chi-like motif. Compared to the
      equivalent regions of other human genes, the MSH2 upstream region was found to
      contain a high density of Alu repeats (30% within 228 kb and 43% within 50 kb),
      most of which belong to the old Alu S subfamilies. In conclusion, this study
      demonstrates the heterogeneity of the breakpoints within the MSH2 upstream region
      and reveals the remarkable density of recombinogenic Alu sequences in this
      region.

PMID- 16086323
TI  - Reorganization of actin cytoskeleton by FRIED, a Frizzled-8 associated protein
      tyrosine phosphatase.
AB  - Frizzled receptors transduce signals from the extracellular Wnt ligands through
      multiple signaling pathways that affect cytoskeletal organization and regulate
      gene expression. Direct intracellular mediators of Frizzled signaling are largely
      unknown. We identified FRIED (Frizzled interaction and ectoderm defects) by its
      association with the C-terminal PDZ-binding motif of Xenopus Frizzled 8. FRIED
      contains an N-terminal KIND domain, a FERM domain, six PDZ domains, and a
      tyrosine phosphatase domain, being similar in structure to the protein tyrosine
      phosphatase PTP-BAS/PTP-BL. We report that FRIED proteins with the FERM domain
      localize to the apical cortex and can inhibit Wnt8-mediated, but not beta-catenin
      mediated, secondary axis induction in Xenopus embryos, suggesting a specific
      interaction with Wnt signaling. A FRIED construct containing the FERM domain
      induced reorganization of pigment granules and cortical actin in Xenopus
      ectoderm. Wnt5a suppressed the depigmentation of ectoderm triggered by FRIED,
      demonstrating that Wnt5a and FRIED functionally interact to regulate the
      cytoskeletal organization. Our data are consistent with the possibility that
      FRIED functions by modulating Rac1 activity. We propose that FRIED is an adaptor
      protein that serves as a molecular link between Wnt signaling and actin
      cytoskeleton.

PMID- 16086324
TI  - Comparison of yield and genotyping performance of multiple displacement
      amplification and OmniPlex whole genome amplified DNA generated from multiple DNA
      sources.
AB  - The promise of whole genome amplification (WGA) is that genomic DNA (gDNA)
      quantity will not limit molecular genetic analyses. Multiple displacement
      amplification (MDA) and the OmniPlex PCR-based WGA protocols were evaluated using
      4 and 5 ng of input gDNA from 60 gDNA samples from three tissue sources
      (mouthwash, buffy coat, and lymphoblast). WGA DNA (wgaDNA) yield and genotyping
      performance were evaluated using genotypes determined from gDNA and wgaDNA using
      the AmpFlSTR Identifiler assay and N = 49 TaqMan SNP assays. Short tandem repeat
      (STR) and SNP genotyping completion and concordance rates were significantly
      reduced with wgaDNA from all WGA methods compared with gDNA. OmniPlex wgaDNA
      exhibited a greater reduction in genotyping performance than MDA wgaDNA. Reduced
      wgaDNA genotyping performance was due to allelic (all protocols) and locus
      (OmniPlex) amplification bias leading to heterozygote and locus dropout,
      respectively, and %GC sequence content (%GC) was significantly correlated with
      TaqMan assay performance. Lymphoblast wgaDNA exhibited higher yield (OmniPlex),
      buffy coat wgaDNA exhibited higher STR genotyping completion (MDA), whereas
      mouthwash wgaDNA exhibited higher SNP genotyping discordance (MDA). Genotyping of
      wgaDNA generated from < or = 5 ng gDNA, e.g., from archaeological, forensic,
      prenatal diagnostic, or pathology samples, may require additional genotyping
      validation with gDNA and/or more sophisticated analysis of genotypes
      incorporating observed reductions in genotyping performance.

PMID- 16086325
TI  - Gaucher mutation N188S is associated with myoclonic epilepsy.
AB  - The recent article by Montfort et al. [2004] reported a functional analysis of 13
      glucocerebrosidase alleles, including mutation N188S, which they considered to be
      a "very mild mutation" or "modifier variant." Our clinical experience with
      patients carrying this mutation and preliminary protein modeling data lead us to
      dispute this conclusion.

PMID- 16086329
TI  - PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders.
AB  - Diseases of the Zellweger spectrum represent a major subgroup of the peroxisome
      biogenesis disorders, a group of autosomal-recessive diseases that are
      characterized by widespread tissue pathology, including neurodegeneration. The
      Zellweger spectrum represents a clinical continuum, with Zellweger syndrome (ZS)
      having the most severe phenotype, and neonatal adrenoleukodystrophy (NALD) and
      infantile Refsum disease (IRD) having progressively milder phenotypes. Mutations
      in the PEX1 gene, which encodes a 143-kDa AAA ATPase protein required for
      peroxisome biogenesis, are the most common cause of the Zellweger spectrum
      diseases. The PEX1 mutations identified to date comprise insertions, deletions,
      nonsense, missense, and splice site mutations. Mutations that produce premature
      truncation codons (PTCs) are distributed throughout the PEX1 gene, whereas the
      majority of missense mutations segregate with the two essential AAA domains of
      the PEX1 protein. Severity at the two ends of the Zellweger spectrum correlates
      broadly with mutation type and impact (i.e., the severe ZS correlates with PTCs
      on both alleles, and the milder phenotypes correlate with missense mutations),
      but exceptions to these general correlations exist. This article provides an
      overview of the currently known PEX1 mutations, and includes, when necessary,
      revised mutation nomenclature and genotype-phenotype correlations that may be
      useful for clinical diagnosis.

PMID- 16086330
TI  - Understanding and optimizing the amplitude modulated control for multiple-slice
      continuous arterial spin labeling.
AB  - Multiple-slice perfusion imaging by continuous arterial spin labeling (CASL) is
      made possible by amplitude modulation (AM) of the labeling RF pulse, but
      perfusion sensitivity is reduced relative to the single-slice technique. A
      computer model of the Bloch equations for velocity driven adiabatic fast passage
      was developed to elucidate the compromised sensitivity to perfusion of the AM
      control technique for CASL. Calculations were performed over ranges of RF pulse
      amplitude, B1; magnetic field gradient, G; phase, phi, and frequency, f, of the
      modulation function; velocity, v, and relaxation times, T1 and T2, of blood. It
      was found that unless f>2piB1, phi determines the performance of the AM control;
      excessively high B1 or v reduces the efficiency of the AM control; and T1
      relaxation dominates if f is too great. In vivo, in rat brain (n=5) at 2.35 T,
      the sensitivity of the AM technique to perfusion was 70% of the sensitivity of
      single-slice CASL.

PMID- 16086331
TI  - Isolation and characterization of the laure olfactory behavioral mutant in the
      zebrafish, Danio rerio.
AB  - To initiate a genetic analysis of olfactory development and function in the
      zebrafish, Danio rerio, we developed a behavioral genetic screen for mutations
      affecting the olfactory sensory system. First, we characterized olfactory
      responses of wild-type zebrafish to various odors. We found that 3-day-old
      juvenile zebrafish reacted to the amino acid L-cysteine with an aversive
      behavioral response. We isolated one mutant, laure (lre), which showed no
      aversive behavioral response to L-cysteine at 3 days of development, and carried
      out a preliminary characterization of this mutant's defects. We found that lre
      mutant fish were also defective in their response to L-serine and L-alanine, but
      not to taurocholic acid, as young adults. In addition, lre mutant fish had
      significantly fewer primary olfactory sensory neurons than normal, and the axons
      of these neurons did not form the characteristic axon termination pattern in the
      developing olfactory bulb. Nevertheless, the olfactory epithelium of lre mutant
      fish showed normal or near normal electrophysiological responses to several
      odorants. Our data suggest that the behavioral defects observed in the lre mutant
      result from the disruption of the developing olfactory sensory neurons and their
      axonal connections within the olfactory bulb. The isolation of the lre mutant
      shows that our behavior-based screen represents a viable approach for carrying
      out a genetic dissection of olfactory behaviors in this vertebrate model system.

PMID- 16086332
TI  - Induction of apoptosis involving multiple pathways is a primary response to
      cyclin A1-deficiency in male meiosis.
AB  - The meiotic arrest in male mice null for the cyclin A1 gene (Ccna1) was
      associated with apoptosis of spermatocytes. To determine whether the apoptosis in
      spermatocytes was triggered in response to the arrest at G2/M phase, as opposed
      to being a secondary response to overall disruption of spermatogenesis, we
      examined testes during the first wave of spermatogenesis by terminal
      deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling
      (TUNEL) staining. We observed enhanced apoptosis coinciding with the arrest point
      in postnatal day 22 tubules, with no overt degeneration. Along with activation of
      caspase-3, an increase in the levels and change of subcellular localization of
      Bax protein was observed in cyclin A1-deficient spermatocytes, which coincided
      with the detection of apoptosis. As p53 is implicated in the activation of Bax
      mediated cell death, we generated mice lacking both cyclin A1 and p53. Although
      the absence of p53 did not rescue the meiotic arrest, there was a decrease in the
      number of apoptotic cells in the double-mutant testes. This finding suggested
      that p53 may be involved in the process by which the arrested germ cells are
      removed from the seminiferous tubules but that other pathways function as well to
      ensure removal of the arrested spermatocytes.

PMID- 16086333
TI  - Experimental and computational studies of intracomplex reactions in Mg+(primary,
      secondary alkylamine) complexes induced by photoexcitation of Mg+.
AB  - We report herein a comprehensive study of photoinduced reactions in complexes of
      Mg+ with primary (n-propyl- and isopropylamine) and secondary amines (dipropyl-
      and diisopropylamine) in the spectral range of 230-440 nm. Similar to the methyl-
      and ethylamine complexes studied previously, N-H bond activation of these
      complexes is very unfavorable. Instead, the C(alpha)-C, C-N, and C(alpha)-H bond
      cleavage photoproducts are observed after photoexcitation of the Mg+ complexes
      (3(2)P<--3(2)S). For Mg+(primary amine) complexes, for example, Mg+-NH2CH2CH2CH3,
      and Mg+-NH2CH(CH3)2, the photoproducts resulting from C(alpha)--C rupture prevail
      after P(z) and charge-transfer excitations, whereas the Mg+ photofragment is
      predominant upon P(x,y) excitation. However, with further N-alkyl substitution,
      as in Mg+(secondary amine) complexes, for example, Mg+-NH(CH2CH2CH3)2 and Mg+
      NH[CH(CH3)2]2, a novel intracomplex C-C coupling photoreaction dominates on
      P(x,y) excitation of Mg+, which is believed to arise from Mg+* insertion into the
      C-N bond. With P(z) and charge-transfer excitation, the Mg-R elimination
      photoproducts, arising from C(alpha)-C bond cleavage, predominate. The energetics
      and possible mechanisms of the intracomplex photoreactions are analyzed in detail
      with the help of extensive quantum mechanics calculations.

PMID- 16086334
TI  - Bifunctional organometallic catalysts involving proton transfer or hydrogen
      bonding.
AB  - Inspired by the cooperativity displayed by metalloenzymes, bifunctional
      organometallic complexes featuring pendant basic functional groups are designed
      and evaluated as catalysts in reactions for which enzymes are not suited. Anti
      Markovnikov hydration of terminal alkynes is the focus, as are hydrogen bonding
      and proton transfer facilitated by the pendant groups.

PMID- 16086335
TI  - Charge-shift bonding--a class of electron-pair bonds that emerges from valence
      bond theory and is supported by the electron localization function approach.
AB  - This paper deals with a central paradigm of chemistry, the electron-pair bond.
      Valence bond (VB) theory and electron-localization function (ELF) calculations of
      21 single bonds demonstrate that along the two classical bond families of
      covalent and ionic bonds, there exists a class of charge-shift bonds (CS bonds)
      in which the fluctuation of the electron pair density plays a dominant role. In
      VB theory, CS bonding manifests by way of a large covalent-ionic resonance
      energy, RE(CS), and in ELF by a depleted basin population with large variances
      (fluctuations). CS bonding is shown to be a fundamental mechanism that is
      necessary to satisfy the equilibrium condition, namely the virial ratio of the
      kinetic and potential energy contributions to the bond energy. The paper defines
      the atomic propensity and territory for CS bonding: Atoms (fragments) that are
      prone to CS bonding are compact electronegative and/or lone-pair-rich species. As
      such, the territory of CS bonding transcends considerations of static charge
      distribution, and involves: a) homopolar bonds of heteroatoms with zero static
      ionicity, b) heteropolar sigma and pi bonds of the electronegative and/or
      electron-pair-rich elements among themselves and to other atoms (e.g., the higher
      metalloids, Si, Ge, Sn, etc), c) all hypercoordinate molecules. Several
      experimental manifestations of charge-shift bonding are discussed, such as
      depleted bonding density, the rarity of ionic chemistry of silicon in condensed
      phases, and the high barriers of halogen-transfer reactions as compared to
      hydrogen-transfers.

PMID- 16086336
TI  - Two-photon dyes containing heterocyclic rings with enhanced photostability.
AB  - A series of donor-pi-donor derivatives containing phenyl, naphthyl, and anthryl
      groups as the pi-center and heterocyclic rings as the conjugation bridge have
      been synthesized and their one- and two-photon spectroscopic properties and
      photostability were determined. These compounds show bathochromic shifts in the
      absorption and emission spectra, larger two-photon cross-section, and enhanced
      photostability in comparison to their open-chain analogues. In addition, a
      convenient method for the qualitative photostability measurement is proposed.

PMID- 16086337
TI  - Organolanthanide-mediated intermolecular hydroamination of 1,3-dienes:
      mechanistic insights from a computational exploration of diverse mechanistic
      pathways for the stereoselective hydroamination of 1,3-butadiene with a primary
      amine supported by an ansa-neodymocene-based catalyst.
AB  - The complete catalytic reaction course for the organolanthanide-mediated
      intermolecular hydroamination of 1,3-butadiene and n-propylamine by an
      archetypical [Me2Si(eta5-Me4C5)2NdCH(SiMe3)2] precatalyst was critically
      scrutinized by employing a reliable gradient-corrected DFT method. A free-energy
      profile of the overall reaction is presented that is based on the thorough
      characterization of all crucial elementary steps for a tentative catalytic cycle.
      A computationally verified, revised mechanistic scenario is proposed which is
      consistent with the experimentally derived empirical rate law and accounts for
      crucial experimental observations. It involves kinetically mobile reactant
      association/dissociation equilibria and facile, reversible intermolecular diene
      insertion into the Nd-amido bond, linked to turnover-limiting protonolysis of the
      eta3-butenyl-Nd functionality. The computationally predicted effective kinetics
      (Delta(tot) = 11.3 kcal mol(-1), Delta(tot) = -35.7 e.u.) are in reasonably good
      agreement with experimental data for the thoroughly studied hydroamination of
      alkynes. The thermodynamic and kinetic factors that determine the almost complete
      regio- and stereoselectivity of the mechanistically diverse intermolecular 1,3
      diene hydroamination have been unraveled. The present computational study
      complements experiments because it allows, first, a more detailed understanding
      and a consistent rationalization of the experimental results for the
      hydroamination of 1,3-dienes and primary amines and, second, enhances the
      insights into general mechanistic aspects of organolanthanide-mediated
      intermolecular hydroamination.

PMID- 16086338
TI  - Boron as a bridging ligand.
AB  - The Lewis acidity of [(eta5-C5R5)Fe(CO)2(BX2)] (1: R = H, X = Cl) and the robust
      nature of the constituent Fe--B bond have been demonstrated by reaction with 4
      methylpyridine to yield the corresponding Lewis acid-base adduct. These
      properties have subsequently been utilised in the construction of heterodinuclear
      bridging borylene, bridging boryl and mu(2)-boride complexes from analogues 3 (R
      = Me, X = Br) and 5 (R = Me, X = Cl). All the bimetallic species so formed
      exhibited unprecedented coordination modes for boron.

PMID- 16086339
TI  - A photoactive molecular triad as a nanoscale power supply for a supramolecular
      machine.
AB  - A tetrathiafulvalene-porphyrin-fullerene (TTF-P-C(60)) molecular triad, which
      generates electrical current by harnessing light energy when self-assembled onto
      gold electrodes, has been developed. The triad, composed of three unique
      electroactive components, namely, 1) an electron-donating TTF unit, 2) a
      chromophoric porphyrin unit, and 3) an electron-accepting C(60) unit, has been
      synthesized in a modular fashion. A disulfide-based anchoring group was tagged to
      the TTF end of the molecule in order to allow its self-assembly on gold surfaces.
      The surface coverage by the triad in a self-assembled monolayer (SAM) was
      estimated to be 1.4 nm(2) per molecule, a density which is consistent with
      hexagonal close-packing of the spherical C(60) component (diameter approximately
      1 nm). In a closed electronic circuit, a triad-SAM functionalized working
      electrode generates a switchable photocurrent of approximately 1.5 microA cm(-2)
      when irradiated with a 413 nm Kr-ion laser, a wavelength which is close to the
      porphyrin chromophore's absorption maximum peak at 420 nm. The electrical energy
      generated by the triad at the expense of the light energy is ultimately exploited
      to drive a supramolecular machine in the form of a [2]pseudorotaxane comprised of
      a pi-electron-deficient tetracationic cyclobis(paraquat-p-phenylene) (CBPQT(4+))
      cyclophane and a pi-electron-rich 1,5-bis[(2-hydroxyethoxy) ethoxy]naphthalene
      (BHEEN) thread. The redox-induced dethreading of the CBPQT(4+) cyclophane from
      the BHEEN thread can be monitored by measuring the increase in the fluorescence
      intensity of the BHEEN unit. A gradual increase in the fluorescence intensity of
      the BHEEN unit concomitant with the photocurrent generation, even at a potential
      (0 V) much lower than that required (-300 mV) for the direct reduction of the
      CBPQT(4+) unit, confirms that the dethreading process is driven by the
      photocurrent generated by the triad-SAM.

PMID- 16086340
TI  - Interplay between intra- and interligand charge transfer with variation of the
      axial N-heterocyclic ligand in osmium(II) pyridylpyrazolate complexes: extensive
      color tuning by phosphorescent solvatochromism.
AB  - The rational design and syntheses of a new series of Os(II) complexes with
      formula [Os(fppz)(2)(CO)(L)] (1: L=4-dimethylaminopyridine; 2: L = pyridine; 3: L
      = 4,4'-bipyridine; 4: L = pyridazine; 5: L = 4-cyanopyridine), bearing two (2
      pyridyl)pyrazolate ligands (fppz) together with one carbonyl and one N
      heterocyclic ligand at the axial positions are reported. Single-crystal X-ray
      diffraction studies of, for example, 2 reveal a distorted octahedral geometry in
      which both fppz ligands reside in the equatorial plane with a trans configuration
      and adopt a bent arrangement at the metal center with a dihedral angle of
      approximately 23 degrees , while the carbonyl and pyridine ligands are located at
      the axial positions. Variation of the axial N-heterocyclic ligand leads to
      remarkable changes in the photophysical properties as the energy gap and hence
      the phosphorescence peak wavelength can be tuned. For complexes 1 and 2 the
      solvent-polarity-independent phosphorescence originates from a combination of
      intraligand (3)pi-pi* ((3)ILCT) and metal-to-ligand charge transfer transitions
      ((3)MLCT). In sharp contrast, as supported by cyclic voltammetry measurements and
      theoretical calculations, complexes 3--5 exhibit mainly ligand-to-ligand charge
      transfer (LLCT) transitions, resulting in a large dipolar change. The
      phosphorescence of complexes 3--5 thus exhibits a strong dependence on the
      polarity of the solvent, being shifted for example, from 560 (in C(6)H(12)) to
      665 nm (in CH(3)CN) and from 603 (in C(6)H(12)) to 710 nm (in CH(3)CN) for
      complexes 3 and 5, respectively. The results clearly demonstrate that a simple,
      straightforward derivatization of the axial N-heterocyclic ligand drastically
      alters the excitation properties per se from intraligand charge transfer (ILCT)
      to LLCT transitions. The latter exhibit remarkable LLCT phosphorescence
      solvatochromism so that a broad range of color tunability can be achieved.

PMID- 16086341
TI  - Polyamorphism in silicon nanocrystals under pressure.

PMID- 16086342
TI  - Dual-scale modeling of benzene adsorption onto Ni(111) and Au(111) surfaces in
      explicit water.
AB  - We present a multiscale modeling approach for studying interactions of organic
      molecules with metal surfaces in explicit water. The approach is based on
      combining adsorption energies of isolated molecules on transition metal surfaces
      calculated by ab initio density functional methods and classical molecular
      dynamics simulations using atomistically detailed force fields. The interaction
      of benzene with Ni(111) and Au(111) surfaces was studied. It is shown that a
      strong affinity of water for the hydrophilic surfaces makes benzene adsorption on
      Au thermodynamically unfavorable, while on Ni there is no preference. The work
      presented here serves as a first step in modeling the interactions of larger
      organic molecules with metal surfaces.

PMID- 16086343
TI  - Generalized hybrid-orbital method for combining density functional theory with
      molecular mechanicals.
AB  - The generalized hybrid orbital (GHO) method has previously been formulated for
      combining molecular mechanics with various levels of quantum mechanics, in
      particular semiempirical neglect of diatomic differential overlap theory, ab
      initio Hartree-Fock theory, and self-consistent charge density functional tight
      binding theory. To include electron-correlation effects accurately and
      efficiently in GHO calculations, we extend the GHO method to density functional
      theory in the generalized-gradient approximation and hybrid density functional
      theory (denoted by GHO-DFT and GHO-HDFT, respectively) using Gaussian-type
      orbitals as basis functions. In the proposed GHO-(H)DFT formalism, charge
      densities in auxiliary hybrid orbitals are included to calculate the total
      electron density. The orthonormality constraints involving the auxiliary Kohn
      Sham orbitals are satisfied by carrying out the hybridization in terms of a set
      of Lowdin symmetrically orthogonalized atomic basis functions. Analytical
      gradients are formulated for GHO-(H)DFT by incorporating additional forces
      associated with GHO basis transformations. Scaling parameters are introduced for
      some of the one-electron integrals and are optimized to obtain the correct
      charges and geometry near the QM/MM boundary region. The GHO-(H)DFT method based
      on the generalized gradient approach (GGA) (BLYP and mPWPW91) and HDFT methods
      (B3 LYP, mPW1PW91, and MPW1 K) is tested-for geometries and atomic charges
      against a set of small molecules. The following quantities are tested: 1) the C-
      C stretch potential in ethane, 2) the torsional barrier for internal rotation
      around the central C--C bond in n-butane, 3) proton affinities for a set of
      alcohols, amines, thiols, and acids, 4) the conformational energies of alanine
      dipeptide, and 5) the barrier height of the hydrogen-atom transfer between n
      C4H10 and n-C4H9, where the reaction center is described at the MPW1 K/6-31G(d)
      level of theory.

PMID- 16086344
TI  - Density of configurational states from first-principles calculations: the phase
      diagram of Al-Na surface alloys.
AB  - The structural phases of Al(x)Na(1-x) surface alloys have been investigated
      theoretically and experimentally. We describe the system using a lattice-gas
      Hamiltonian, determined from density functional theory, together with Monte Carlo
      (MC) calculations. The obtained phase diagram reproduces the experiment on a
      quantitative level. From calculation of the (configurational) density of states
      by the recently introduced Wang-Landau MC algorithm, we derive thermodynamic
      quantities, such as the free energy and entropy, which are not directly
      accessible from conventional MC simulations. We accurately reproduce the
      stoichiometry, as well as the temperature at which an order-disorder phase
      transition occurs, and demonstrate the crucial role, and magnitude, of the
      configurational entropy.

PMID- 16086345
TI  - Orbital magnetization in extended systems.
AB  - While the orbital magnetic dipole moment of any finite sample is well-defined, it
      becomes ill-defined in the thermodynamic limit as a result of the unboundedness
      of the position operator. Effects due to surface currents and to bulk
      magnetization are not easily disentangled. The corresponding electrical problem,
      where surface charges and bulk polarization appear as entangled, was solved about
      a decade ago by the modern theory of polarization, based on a Berry phase. We
      follow a similar path here, making progress toward a bulk expression for the
      orbital magnetization in an insulator represented by a lattice-periodic
      Hamiltonian with broken time-reversal symmetry. We therefore limit ourselves to
      the case where the macroscopic (i.e. cell-averaged) magnetic field vanishes. We
      derive an expression for the contribution to the magnetization arising from the
      circulating currents internal to the bulk Wannier functions, and then transform
      to obtain a Brillouin zone integral involving the occupied Bloch orbitals. A
      version suitable for practical implementation in discretized reciprocal space is
      also derived, and the gauge invariance of both versions is explicitly shown.
      However, tests on a tight-binding model indicate the presence of additional edge
      currents, and it remains to be determined whether these can be related to the
      bulk band structure.

PMID- 16086346
TI  - Car-Parrinello molecular dynamics on massively parallel computers.

PMID- 16086347
TI  - Models of putative (AH)G(AH)G nucleobase quartets.

PMID- 16086348
TI  - Modeling the anodic half-cell of a low-temperature coal fuel cell.

PMID- 16086349
TI  - PbTe nanorods by sonoelectrochemistry.

PMID- 16086350
TI  - A functional assay for heparin in serum using a designed synthetic receptor.

PMID- 16086351
TI  - Energetics and mechanism of a room-temperature catalytic process for ammonia
      synthesis (Schrock cycle): comparison with biological nitrogen fixation.

PMID- 16086352
TI  - Photo-cross-coupling reaction of electron-rich aryl chlorides and aryl esters
      with alkynes: a metal-free alkynylation.

PMID- 16086353
TI  - Stereoselective synthesis of highly substituted cyclopentenones through [4+1]
      annulations of trialkylsilyl vinyl ketenes with alpha-benzotriazolyl
      organolithium compounds.

PMID- 16086355
TI  - From concentration profiles to polymer osmotic equations of state.

PMID- 16086354
TI  - Efficient one-step synthesis of biologically related lariat RNAs by a
      deoxyribozyme.

PMID- 16086356
TI  - Intermolecular electronic excitation transfer in a confined space: a first
      principles study.
AB  - The process of intermolecular electronic excitation transfer (EET) in a
      monodimensional supramolecular arrangement of molecules in confined space has
      been modelled and investigated by means of first-principles molecular dynamics
      simulations. The chosen model system consists of a wire of chlorine molecules
      hosted in the noncrossing channels of the zeolite bikitaite. The time evolution
      of the system in its first excited singlet state has been described by the
      restricted open shell Kohn-Sham formalism. Simulation results have highlighted
      that excitation, initially localized on a guest molecule, is transferred to an
      adjacent moiety in the molecular wire on the picosecond scale via a collision
      induced Dexter-type short range EET. Analysis of the modifications of the
      electronic structure of the system brought about by EET has given insight into
      the microscopic details of the process.

PMID- 16086357
TI  - Car-Parrinello molecular dynamics study of a blue-shifted intermolecular weak
      hydrogen-bond system.

PMID- 16086358
TI  - Excited-state dynamics and coupled proton-electron transfer of Guanine.

PMID- 16086359
TI  - Localization of Apaf1 gene expression in the early development of the mouse by
      means of in situ reverse transcriptase-polymerase chain reaction.
AB  - Apoptosis is an essential ubiquitous process that controls the duration of the
      life span of cells, thus playing a crucial role in morphogenetic, histogenetic,
      and phylogenetic developmental processes. Apaf1 (apoptosis protease activating
      factor 1) is one of the central mediators of the intrinsic apoptotic pathway and
      a part of the apoptosome, which activates procaspase-3 and promotes cell death.
      Gene knockout of Apaf1 in mice leads to late embryonic lethality with
      malformations such as the persistence of interdigital webs and hyperplasia of
      brain and retina. Therefore, Apaf1 is generally believed to play a crucial role
      in developmental apoptosis and have a widespread expression. However, its pattern
      of expression in early development remains unknown. To specify whether Apaf1
      indeed plays this key role, we investigated the pattern of gene expression for
      Apaf1 in mouse embryos on day 7, 9, and 12 of development. Our results show, that
      gene expression for Apaf1 first occurs within the embryo between day 7 and 9 of
      development, becoming more widespread toward day 12 and then includes structures,
      such as yolk sac, mesenchyme, cartilage, heart anlage, otic vesicle, peridermis,
      and anlagen of the spinal ganglia and vertebral bodies. Our results also show
      that gene expression for Apaf1 is not ubiquitous in early mouse development. This
      finding indicates that cell death processes are independent of or less dependent
      on Apaf1 during this time. Of interest, an active gene expression for Apaf1 is
      also present in organ anlagen such as heart or intestine, in which no obvious
      phenotype is seen after Apaf1 deletion. This finding suggests a possible role for
      Apaf1 in such anlagen as a putative alternative compensatory pathway, which could
      be switched on in the case of defects in the mediators that are normally involved
      in such organs.

PMID- 16086360
TI  - SALL4 mutations in Okihiro syndrome (Duane-radial ray syndrome), acro-renal
      ocular syndrome, and related disorders.
AB  - Okihiro/Duane-radial ray syndrome (DRRS) is an autosomal dominant condition
      characterized by radial ray defects and Duane anomaly (a form of strabismus).
      Other abnormalities reported in this condition are anal, renal, cardiac, ear, and
      foot malformations, and hearing loss. The disease is the result of a mutation in
      the SALL4 gene, a human gene related to the developmental regulator spalt (sal)
      of Drosophila melanogaster. SALL4 mutations may also cause acro-renal-ocular
      syndrome (AROS), which differs from DRRS by the presence of structural eye
      anomalies, and phenotypes similar to thalidomide embryopathy and Holt-Oram
      syndrome (HOS). The SALL4 gene product is a zinc finger protein that is thought
      to act as a transcription factor. It contains three highly conserved C2H2 double
      zinc finger domains, which are evenly distributed. A single C2H2 motif is
      attached to the second domain, and at the amino terminus SALL4 contains a C2HC
      motif. Seventeen of the 22 SALL4 mutations known to date (five of which are
      presented here for the first time) are located in exon 2, and five are located in
      exon 3. These are nonsense mutations, short duplications, and short deletions.
      All of the mutations lead to preterminal stop codons and are thought to cause the
      phenotype via haploinsufficiency. This assumption is supported by the detection
      of six larger deletions involving the whole gene or single exons. This article
      summarizes the current knowledge about SALL4 defects and associated syndromes,
      and describes the clinical distinctions with similar phenotypes caused by other
      gene defects.

PMID- 16086361
TI  - Development of ultra short-acting muscle relaxant agents: history, research
      strategies, and challenges.
AB  - Author has reviewed the literature and his own work related to the chemistry,
      pharmacology, and clinical aspects of new muscle relaxants. Emphasis has been
      placed on the basic science concepts and technologies (e.g. structure-activity
      relationships, nicotinic receptor pharmacology, and investigation of side
      effects) behind the development of rapidly and short acting nondepolarizing
      muscle relaxants.

PMID- 16086362
TI  - Broadband multicoil imaging using multiple demodulation hardware: a feasibility
      study.
AB  - Multiple receiver-coil data collection is an effective approach to reduce scan
      time. There are many parallel imaging techniques that reduce scan time using
      multiple receiver coils. One of these methods, partially parallel imaging with
      localized sensitivities (PILS), utilizes the localized sensitivity of each coil.
      The advantages of PILS over other parallel imaging methods include the simplicity
      of the algorithm, good signal-to-noise ratio (SNR) properties, and the fact that
      there is no additional complexity involved in applying the algorithm to arbitrary
      k-space trajectories. This PILS method can be further improved to provide truly
      parallel broadband imaging with the use of multiple-demodulation hardware. By
      customizing the demodulation based on each coil's location, the k-space sampling
      rate can be chosen based on each coil's localized sensitivity region along the
      readout direction. A simulated demodulation of data from 2D Fourier transform
      (FT) and spiral trajectories is shown to demonstrate the method's feasibility.

PMID- 16086363
TI  - Biexponential parameterization of diffusion and T2 relaxation decay curves in a
      rat muscle edema model: decay curve components and water compartments.
AB  - Quantitative T2 relaxation and diffusion imaging studies of a rat muscle edema
      model were performed in order to determine the effects of intra- and
      extracellular water compartmentation on the respective decay curves. The right
      hind paw of rats was injected with a carrageenan solution to generate edematous
      muscle. A Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence was used to acquire
      T2 relaxation decay curves from both paws. A line scan diffusion imaging (LSDI)
      sequence was then used to acquire diffusion decay curves from the same paws over
      a wide b-factor range. Measurements were made from both edematous muscle (EM) and
      control muscle (CM). The EM and CM T2 relaxation decay curves were best fit with
      biexponential functions. The fraction of the fast T2 component dropped
      dramatically from approximately 0.95 in CM to 0.45 in EM, consistent with a water
      compartmentation model in which the fast and slow T2 components reflect intra-
      and extracellular water, respectively. Both CM and EM diffusion decay curves
      required biexponential fitting functions, and the diffusion coefficients of the
      fast and slow components were substantially larger in EM than CM. The fraction of
      the fast diffusion component, however, was not radically altered between CM and
      EM conditions (0.84 versus 0.89 for CM versus EM). Assuming a model in which
      intra- and extracellular water compartments are responsible for the fast and slow
      T2-decay components and for the slow and fast diffusion decay components,
      respectively, leads to fractional sizes of the diffusion components that are not
      supported by experiment. We conclude that intra- and extracellular water
      compartmentation is a reasonable interpretation for the two T2-decay components
      in both CM and EM but that other factors, such as restricted diffusion and/or
      alternate forms of water compartmentation like surface versus volume water, most
      probably have profound influences on the precise shapes of the diffusion decay
      curves, a complete understanding of which will require significant theoretical
      work.

PMID- 16086364
TI  - Effects of fexofenadine and hydroxyzine on brake reaction time during car-driving
      with cellular phone use.
AB  - Antihistamines are a mainstay treatment for allergic rhinitis; however, many
      older agents cause adverse events, including sedation and central nervous system
      (CNS) impairment. Research has shown sedating effects of antihistamines on
      driving; currently, no known study has examined whether cellular phone usage
      while driving further compounds impairment in individuals administered
      antihistamines. The aim of this study was to examine this endpoint. In a
      randomized, double-blind, placebo-controlled, three-way crossover study, healthy
      volunteers received fexofenadine HCl 120 mg, hydroxyzine HCl 30 mg and placebo.
      Brake reaction time (BRT) was used to examine driving performance across four
      conditions: driving only; driving while completing simple calculations; complex
      calculations; and conversing on a cellular phone. Subjective sedation assessments
      were also conducted. Brake reaction time with and without cellular phone usage in
      fexofenadine-treated subjects did not differ significantly from placebo in any
      condition. In contrast, hydroxyzine-treated subjects were significantly more
      sedated and had slower BRTs, suggesting slower hazard recognition and brake
      application, compared with the fexofenadine and placebo groups in all conditions.
      Importantly, cellular phone operation was an additive factor, increasing BRTs in
      hydroxyzine-treated volunteers. Fexofenadine did not impair CNS function in
      subjects involved in a divided attention task of driving and cellular phone
      operation.

PMID- 16086365
TI  - UMD (Universal Mutation Database): 2005 update.
AB  - With the completion of the Human Genome Project, our vision of human genetic
      diseases has changed. The cloning of new disease-causing genes can now be
      performed in silico, and thousands of mutations are being identified in
      diagnostic and research laboratories yearly. Knowledge about these mutations and
      their association with clinical and biological data is essential for clinicians,
      geneticists, and researchers. To collect and analyze these data, we developed a
      generic software called Universal Mutation Databases (UMD) to create locus
      specific databases. Here we report the new release (September 2004) of this
      freely available tool (www.umd.be), which allows the creation of LSDBs for
      virtually any gene and includes a large set of new analysis tools. We have
      implemented new features to integrate noncoding sequences, clinical data,
      pictures, monoclonal antibodies, and polymorphic markers (SNPs). Today the UMD
      retains all specifically designed tools to analyze mutations at the molecular
      level, as well as new sets of routines to search for genotype-phenotype
      correlations. We also created specific tools for infrequent mutations such as
      gross deletions and duplications, and deep intronic mutations. A large set of
      dedicated tools are now available for intronic mutations, including methods to
      calculate the consensus values (CVs) of potential splice sites and to search for
      exonic splicing enhancer (ESE) motifs. In addition, we have created specific
      routines to help researchers design new therapeutic strategies, such as exon
      skipping, aminoglycoside read-through of stop codons, or monoclonal antibody
      selection and epitope scanning for gene therapy.

PMID- 16086366
TI  - Role for CXCR2 and CXCL1 on glia in multiple sclerosis.
AB  - As part of a need to understand myelin repair mechanisms, molecular pathways
      underlying oligodendrocyte behavior and central nervous system (CNS)
      remyelination are currently key topics in multiple sclerosis (MS). In the present
      study, we report expression of a chemoattractant receptor of the immune system,
      the chemokine receptor, CXCR2, on normal and proliferating oligodendrocytes in
      active MS lesions. Proliferating oligodendrocytes were occasionally associated
      with reactive astrocytes positive for CXCL1 (GRO-alpha), the ligand for CXCR2.
      CXCL1 expression was not seen on astrocytes in control and normal CNS tissue,
      while CXCR2 expression was constitutive on oligodendrocytes. At the functional
      level, following stimulation with the proinflammatory cytokine, interleukin-1beta
      (IL-1beta), we found high-level synthesis of CXCL1 by human fetal astrocytes in
      vitro. In contrast, human oligodendrocytes in culture expressed the receptor,
      CXCR2, constitutively. We propose that the concurrence of CXCR2 on
      oligodendrocytes and induced CXCL1 on hypertrophic astrocytes in MS provides a
      novel mechanism for recruitment of oligodendrocytes to areas of damage, an
      essential prerequisite for lesion repair in this devastating human condition.

PMID- 16086367
TI  - Magnetic resonance imaging of cardiomyocyte apoptosis with a novel magneto
      optical nanoparticle.
AB  - The ability to image cardiomyocyte apoptosis in vivo with high-resolution MRI
      could facilitate the development of novel cardioprotective therapies. The
      sensitivity of the novel nanoparticle AnxCLIO-Cy5.5 for cardiomyocyte apoptosis
      was thus compared in vitro to that of annexin V-FITC and showed a high degree of
      colocalization. MRI was then performed, following transient coronary artery (LAD)
      occlusion, in five mice given AnxCLIO-Cy5.5 and in four mice given an identical
      dose (2 mg Fe/kg) of CLIO-Cy5.5. MR signal intensity and myocardial T2* were
      evaluated, in vivo, in hypokinetic regions of myocardium in the LAD distribution.
      Ex vivo fluorescence imaging was performed to confirm the in vivo findings.
      Myocardial T2* was significantly lower in the mice given AnxCLIO-Cy5.5 (8.1
      versus 13.2 ms, P<0.01), and fluorescence target to background ratio was
      significantly higher (2.1 versus 1.1, P<0.01). This study thus demonstrates the
      feasibility of obtaining high-resolution MR images of cardiomyocyte apoptosis in
      vivo with the novel nanoparticle, AnxCLIO-Cy5.5.

PMID- 16086368
TI  - 19F MR imaging of ventilation and diffusion in excised lungs.
AB  - Perfluorinated gases, particularly C2F6, are potentially suitable alternatives to
      hyperpolarized noble gases for pulmonary airspace spin density and diffusion MRI.
      This work focuses mainly on 19F imaging of C2F6 gas in healthy and emphysematous
      explanted lungs, avoiding regulatory issues of human in vivo measurements. Three
      dimensional gradient echo and spin echo spin density images of human lungs can be
      made in 10 s with adequate signal-to-noise, demonstrating the feasibility for
      breathing dynamics to be captured during a succession of short breath holds. As
      expected, the spin echo images have much smaller susceptibility artifacts than
      the gradient echo images. 19F and 3He images of the same lungs are compared. The
      apparent diffusion coefficient (ADC) of C2F6 is sensitive to restrictions imposed
      by the lung microstructure: the average ADC is measured to be 0.018 cm2/s in
      healthy lungs versus 0.031 cm2/s in emphysematous lungs at a diffusion time
      Delta=2.2 ms. The low free diffusivity of pure C2F6 (D0=0.033 cm2/s) places it in
      a regime where the ADC measurement allows the surface-to-volume ratio to be
      determined in each voxel, a potentially valuable quantitative characterization of
      regional lung tissue destruction in emphysema.

PMID- 16086369
TI  - Transverse relaxation of cells labeled with magnetic nanoparticles.
AB  - We describe the NMR relaxation properties of magnetically labeled cells. The
      cells are labeled with magnetic nanoparticles (SPIO, USPIO), which generate
      susceptibility contrast. The geometry of the labeled cells and the surrounding
      tissue is considered. We assume that the magnetic nanoparticles accumulate to
      form a magnetic core of radius RC inside the cell. The correlation time tau,
      which describes the motion of spins around this core, is analyzed. Using the
      strong collision approach, explicit expressions are derived for the transverse
      relaxation rate R2* for tissue containing labeled cells as a function of the core
      radius, the diffusion coefficient, and the concentration of the nanoparticles.
      The predictions of this model agree well with numerical simulations and
      experimental data.

PMID- 16086371
TI  - Stable expression of EBERs in immortalized nasopharyngeal epithelial cells
      confers resistance to apoptotic stress.
AB  - Epstein-Barr virus (EBV) infection is closely associated with the development of
      nasopharyngeal carcinoma (NPC). The EBV-encoded RNAs (EBERs) are the most
      abundant EBV transcripts (about 10(7) copies per cell) in EBV infected cells.
      However, the cellular function of EBER expression, particularly in nasopharyngeal
      epithelial cells, remains poorly understood. EBERs acquire secondary structures
      analogous to double-stranded RNA (dsRNA) and may bind to the double-stranded RNA
      dependent protein kinase (PKR) and interfere with its function. Activation of PKR
      involves autophosphorylation resulting in protein synthesis inhibition and
      cellular apoptosis. Induction of cellular apoptosis by activation of PKR may be
      an antiviral response adopted by virally infected cells. We have examined the
      functional properties of EBER expression in an immortalized nasopharyngeal
      epithelial cell line (NP69). Expression of EBERs was achieved by transfecting the
      NP69 cells with an EBER-expressing plasmid, pESK10. The EBER-expressing NP69
      cells attained a higher growth rate compared to cells transfected with control
      plasmid (pcDNA3). However, the EBER-expressing NP69 cells did not form colonies
      in soft agar and were non-tumorigenic in nude mice. To investigate if EBERs may
      protect the nasopharyngeal epithelial cells from apoptotic insults, we treated
      the EBER-expressing NP69 cells with a dsRNA analogue, poly(I).poly(C) (pIC), to
      activate PKR in cells and examined for their responses. Lower level of PKR
      phosphorylation and elevation of Bcl-2 were observed in EBER-expressing NP69
      cells. In addition, other apoptotic markers including the cleaved forms of
      caspase-3 and poly(ADP)ribose polymerase (PARP) were found to be lower in EBER
      expressing NP69 cells after treatment with pIC. Lower phosphorylation levels of
      p38 MAPK (mitogen-activated protein kinase) and c-jun were also observed in EBER
      expressing NP cells. Our results suggest that EBER expression may confer an
      apoptotic-resistant phenotype in immortalized nasopharyngeal epithelial cells.

PMID- 16086372
TI  - Resolution and reproducibility of BOLD and perfusion functional MRI at 3.0 Tesla.
AB  - Visual and somatosensory activation studies were performed on normal subjects to
      compare the spatial discrimination and reproducibility between functional MRI
      (fMRI) methods based on blood oxygen level-dependent (BOLD) and perfusion
      contrast. To allow simultaneous measurement of BOLD and perfusion contrast, a
      dedicated MRI acquisition technique was developed. Repeated experiments of
      sensory stimulation of single digits of the right hand showed an average
      variability of activation amplitude of 25% for BOLD data, and a significantly
      lower variability of 21% for perfusion data. No significant difference in the
      variability of the locus of activity was observed between the BOLD and perfusion
      data. In somatotopy experiments, digits II and V were subjected to passive
      sensory stimulation. Both the BOLD and perfusion data showed substantial overlap
      in the activation patterns from the two digits. In a retinotopy study, two
      stimuli were alternated to excite different patches of V1. Again there was
      substantial overlap between the activation patterns from both stimuli, although
      the perfusion performed somewhat better than the BOLD method. Particularly for
      the visual studies, the overlap in activation patterns was more than expected
      based on the fine-scale retinotopic mapping of cortical activity, suggesting that
      both BOLD and perfusion contrast mechanisms contribute substantially to the point
      spread function (PSF).

PMID- 16086373
TI  - Role of PI3K/Akt signaling in insulin-like growth factor-1 (IGF-1) skin tumor
      promotion.
AB  - Overexpression of human IGF-1 with the bovine keratin 5 (BK5) promoter (BK5.IGF-1
      transgenic mice) induces persistent epidermal hyperplasia and leads to
      spontaneous skin tumor formation. In previous work, PI3K and Akt activities were
      found to be elevated in the epidermis of BK5.IGF-1 transgenic mice compared to
      nontransgenic littermates. In the present study, we examined the importance of
      the PI3K/Akt signaling pathway in mediating the skin phenotype and the skin tumor
      promoting action of IGF-1 in these mice. Western blot analyses with epidermal
      lysates showed that signaling components downstream of PI3K/Akt were altered in
      epidermis of BK5.IGF-1 mice. Increased phosphorylation of GSK-3 (Ser(9/21)),
      TSC2(Thr(1462)), and mTOR(Ser(2448)) was observed. In addition,
      hypophosphorylation and increased protein levels of beta-catenin were observed in
      the epidermis of BK5.IGF-1 mice. These data suggested that components downstream
      of Akt might be affected, including cell cycle machinery in the epidermis of
      BK5.IGF-1 mice. Protein levels of cyclins (D1, E, A), E2F1, and E2F4 were all
      elevated in the epidermis of BK5.IGF-1 mice. Also, immunoprecipitation
      experiments demonstrated an increase in cdk4/cyclin D1 and cdk2/cyclin E complex
      formation, suggesting increased cdk activity in the epidermis of transgenic mice.
      In further studies, the PI3K inhibitor, LY294002, significantly blocked IGF-1
      mediated epidermal proliferation and skin tumor promotion in DMBA-initiated
      BK5.IGF-1 mice. In addition, inhibition of PI3K/Akt with LY294002 reversed many
      of the cell cycle related changes observed in untreated transgenic animals.
      Collectively, the current results supported the hypothesis that elevated PI3K/Akt
      activity and subsequent activation of one or more downstream effector pathways
      contributed significantly to the tumor promoting action of IGF-1 in the epidermis
      of BK5.IGF-1 mice.

PMID- 16086375
TI  - Methylguanine methyltransferase activity deficiency in immature rat mammary
      epithelial cells parallels increased carcinogenic susceptibility.
AB  - The prepubertal breast is more susceptible than the mature breast to the
      carcinogenic effects of ionizing radiation, and potentially to cigarette smoke
      and alkylating chemotherapeutics. Mammary epithelial cells (MECs) from sexually
      immature (3-week (wk)-old) Fischer 344 rats were more sensitive than mature (8-wk
      old) rats to the carcinogenic, lethal, and mutagenic effects of N-nitroso-N
      methylurea (NMU). The work reported here was undertaken to better define this age
      specific susceptibility of the mammary gland to NMU. Using the alkaline comet
      assay, it was found that MECs from immature but not mature rats displayed an
      increase in single-strand DNA breaks or alkali-labile lesions 2 h following NMU
      treatment. Hoechst staining indicated apoptosis was not responsible for the
      increase. Inhibition of methylguanine methyltransferase (MGMT) did not affect
      immature MECs but caused mature MECs to recapitulate the immature response to
      NMU. Direct measurement of MGMT activity revealed that immature MECs are
      significantly deficient in MGMT activity relative to mature MECs. MECs had the
      lowest MGMT activity of all organs tested. Immature kidneys, which preferentially
      developed nephroblastomas after NMU treatment, also displayed significantly lower
      MGMT activity than mature kidneys. These results suggest that age-related
      differences in MGMT activity may play a significant role in age-differential
      susceptibility to rat mammary gland and kidney carcinogenesis, and argue the
      importance of extending these studies to humans. They also provide a mechanistic
      basis for studying, as potentially initiating events in breast cancer, exposures
      of prepubertal girls to alkylating agents, to which humans are exposed in
      cigarette smoke, the diet, and as chemotherapy.

PMID- 16086382
TI  - Identification of an X-linked locus modifying mouse skin tumor susceptibility.
AB  - The enhancing effect of overexpression of an ornithine decarboxylase (Odc)
      transgene on skin tumor susceptibility can be modified by genetic loci present in
      several inbred mouse strains. The BALB/cJ strain is among the most resistant
      strains so far examined; tumor multiplicity following 7,12
      dimethylbenz(a)anthracene (DMBA) treatment is reduced by 90% when the K6/ODC
      transgene is expressed on a BALB/cJ background versus the susceptible C57BL/6J
      background. Further, transgenic BALB/cJ males developed more tumors than females,
      indicating the presence of sex-dependent modifier pathway. Analysis of 263 F2
      intercross mice revealed significant linkage of markers on the X chromosome to
      tumor multiplicity. This analyses as well as a similar genome-wide scan of 136
      backcross mice found evidence for other modifier loci on chromosomes 4, 6, and
      17. Identification of these modifier genes should reveal the effector pathways
      responsive to Odc overexpression that mediate susceptibility to skin
      tumorigenesis.

PMID- 16086384
TI  - XXII International Conference on Yeast Genetics and Molecular Biology,
      Bratislava, Slovak Republic. Abstracts.

PMID- 16086389
TI  - Phylogenetic analysis of family 6 glycoside hydrolases.
AB  - Multiple sequence alignment separates members of glycoside hydrolase Family 6
      into eight subfamilies: one of mainly actinobacterial endoglucanases (EGs), one
      of ascomycotal EGs, one of chytridiomycotal EGs and cellobiohydrolases (CBHs),
      one of actinobacterial and proteobacterial CBHs, one of chytridiomycotal CBHs,
      two of ascomycotal CBHs, and one of basidiomycotal CBHs. Each also has some
      proteins of unknown function. Multiple sequence alignment also extends to all of
      Family 6 the observation that lengths of loops that form the active-site tunnel
      in CBHs vary among subfamilies, and along with loop conformations, determine
      enzyme function.

PMID- 16086393
TI  - Gracile bones, periostal appositions, hypomineralization of the cranial vault,
      and mental retardation in brothers: milder variant of osteocraniostenosis or new
      syndrome?
AB  - We report on two brothers with ossification anomalies of membranous and cranial
      bones, remodeling defect of long bones leading to dense, overtubulated, narrow
      diaphyses, metaphyseal flare, periostal hyperosotosis that increased during the
      first months of life, thoracic dystrophy and severe hypotonia. One boy had
      hypospadias and cleft palate. Follow-up of the surviving boy documented
      progressive osteopenia, slow healing of the periostal anomalies, liver
      angiomatosis, mental and motor delay, thoracic deformity, delay in tooth
      eruption, and progressive microcephaly with enlargement of the cerebral
      ventricles. This disorder shares some traits with osteocraniostenosis, but lacks
      the cranial deformity and acromelic micromelia of the latter, in which periostal
      anomalies are not described. The syndrome reported here may represent a milder
      form of osteocraniostenosis, or a new entity belonging to the same "family."
      Genealogical data are consistent with AR or XLR inheritance. No mutations were
      found in the coding sequence of filamin A.

PMID- 16086394
TI  - Marshall-Smith syndrome: natural history and evidence of an osteochondrodysplasia
      with connective tissue abnormalities.
AB  - The Marshall-Smith syndrome (MSS) is a distinct malformation syndrome
      characterized by accelerated skeletal maturation, relative failure to thrive,
      respiratory difficulties, mental retardation, and unusual facies, including
      prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and
      micrognathia. At least 33 cases have been reported in the literature, mostly as
      single case reports or small series. The purpose of the present study is to
      report on the clinical findings and natural history of MSS in five children and
      to review the features of three others previously reported, with particular
      attention to the skeletal and connective tissue findings. Our study demonstrates
      an increased rate of nontraumatic fractures and other bony and connective tissue
      abnormalities that support the hypothesis that MSS should be considered an
      osteochondrodysplasia. In addition, long-term survival beyond infancy is possible
      if respiratory problems are expectantly and aggressively managed.

PMID- 16086395
TI  - Mutation analysis of the HDAC 1, 2, 8 and CDKL5 genes in Rett syndrome patients
      without mutations in MECP2.
AB  - Mutations in the MECP2 gene are found in only 80% of patients with Rett syndrome
      (RTT). Therefore other genes have to be involved in the pathogenesis of RTT. By
      using our defined diagnostic criteria we first re-evaluated 50 girls with
      possible RTT in whom the sequencing of the MECP2 gene had not revealed any
      mutations. Only 15 of theses patients fulfilled all criteria for RTT and could be
      considered to have classical RTT. In eight of these, further molecular analyses
      revealed large deletions of the MECP2 gene. In the remaining seven girls we then
      analyzed the genes HDAC1, HDAC2, and HDAC8 that encode for the histone
      deacetylases 1, 2, and 8 which interact with MeCP2 and are essential for its
      function. Although these histone deacetylase genes have been considered as good
      candidate genes for RTT our molecular analysis of these genes did not detect any
      mutations. Because recently mutations in CDKL5 were reported in patients with
      RTT, we included this gene in our analysis but failed to detect any mutations. We
      conclude that only a subgroup of girls with possible RTT and no detectable
      mutation in the sequencing of the MECP2 gene do really have classical RTT. In
      many of those large MECP2 gene deletions can be detected by further analysis. The
      genes HDAC1, HDAC2, and HDAC8 do not seem to play a role in the pathogenesis of
      RTT and at least in our subgroup no mutations in the CDKL5 gene were detected.

PMID- 16086396
TI  - The outcome of diagnostic studies on the etiology of mental retardation:
      considerations on the classification of the causes.
AB  - In the different studies on the etiology of mental retardation (MR), a diagnosis
      has been reached in a remarkably variable proportion of cases. This is due to
      differences in methodology (population examined, age of the patients, degree of
      MR, time and protocol of investigation, expertise), method of classification
      (according to timing of defect, type of defect or both), and, in particular the
      different use of the term diagnosis. The latter varies with the employed criteria
      (causal vs. pathomorphological vs. pathophysiological), with the degree of
      exclusiveness (single cause vs. multifactorial/predisposing background factors)
      and particularly with the degree of implied certainty (definite vs. provisional).
      All these factors contribute to the fact that in general, the results of
      different clinical studies on the etiology of MR are not strictly comparable and
      cannot be pooled. A dynamic method of classification is proposed which combines
      both time of occurrence and type of defect, and includes the degree of certainty
      of a diagnosis. The method allows identification of patients which need follow-up
      and reconsideration of their cases.

PMID- 16086399
TI  - Astroglial cells in the central nervous system of the adult brown anole lizard,
      Anolis sagrei, revealed by intermediate filament immunohistochemistry.
AB  - We analyzed the distribution of intermediate filament molecular markers, glial
      fibrillary acidic protein (GFAP), and vimentin in the brain and spinal cord of
      the adult brown anole lizard, Anolis sagrei. The GFAP immunoreactivity is strong
      and the positive structures are basically represented by fibers of different
      lengths and thicknesses which are arranged in a regular radial pattern throughout
      the central nervous system. In the brain regions that have a thicker neural wall,
      the radial orientation is not so evident as in the thinner areas. These fibers
      emerge from radial ependymoglia (tanycytes) whose cell bodies are generally GFAP
      immunopositive. The glial fibers give rise to endfeet that are apposed to the
      subpial surface and to blood vessel walls. In the spinal cord, the optic tectum
      and the lateroventral regions of the mesencephalon and medulla oblongata, star
      shaped astrocytes coexist with radial structures. Vimentin-immunoreactive
      structures are absent in the brain and spinal cord. In A. sagrei the
      immunohistochemical response of the astroglial intermediate filaments appears
      typical of a mature astroglial cell lineage, since they fundamentally express
      GFAP immunoreactivity. A Western-blot analysis reveals a GFAP-positive single
      band, common to the different nervous areas. This immunohistochemical study shows
      that the star-shaped astrocytes have a different distribution in saurians and
      while the glial pattern of A. sagrei is more evolved than in urodeles it remains
      immature as compared with crocodilians, avians, and mammals. This condition
      suggests that reptiles represent a fundamental step in the phylogenetic evolution
      of the vertebrate glial cells.

PMID- 16086405
TI  - Sperm structure and phylogeny of Astigmata.
AB  - The Astigmata, a large and variable group, is still a subject of taxonomic
      dispute. Particularly, their origin from ancestors of the lower oribatid mites
      (e.g., Malaconothroidea) seems well documented by many lines of evidence. The
      structure of spermatozoa has been successfully applied to phylogenetic
      investigations in many animal groups. The aim of our study was to provide new
      data on spermatozoon structure in Astigmata and to consider its appropriateness
      in phylogenetic studies. The study reveals information on spermatozoa in 17
      species of Astigmata (11 species studied for the first time) extending our
      knowledge to 18 species (one species known only from the literature) representing
      12 families and 7 superfamilies. Spermatozoa have the same basic structure in all
      species: cells are multiform and the chromatin forms thin threads embedded
      directly in the cytoplasm; the acrosome is absent. The cytoplasm in most species
      contains electron-dense lamellae, varying in both number and arrangement within
      the cell. In Sarcoptoidea, electron-dense tubules in contact with lamellae
      margins were also observed in Psoroptidae (Psoroptes equi), whereas in two
      representatives of Sarcoptidae (Notoedres cati and Sarcoptes scabiei), only
      electron-dense tubules were found. In two species, Canestrinia sellnicki
      (Canestrinioidea: Canestriniidae) and Scutulanyssus obscurus (Analgoidea:
      Pteronyssidae), neither lamellae nor tubules were present. The mitochondria in a
      spermatozoon are usually gathered at the cell periphery and their structure is
      usually modified to form so-called mitochondrial derivatives. The chromatin
      threads are an autapomorphy strongly supporting the monophyly of Astigmata. As
      spermatozoa vary considerably between species in Astigmata, we deduce that sperm
      structure may be useful for phylogenetic analyses within the group. Several
      conclusions concerning the affinities within Astigmata are presented.
      Spermatology seems to be unhelpful, however, in questions on the origin of
      Astigmata (particularly for Astigmata-Oribatida relationships), since their sperm
      do not possess synapomorphies with sperm of the remaining groups of Acariformes,
      i.e., Endeostigmata, Prostigmata, and Oribatida.

PMID- 16086406
TI  - Development and growth of long bones in European water frogs (Amphibia: Anura:
      Ranidae), with remarks on age determination.
AB  - Differentiation and development of long bones were studied in European water
      frogs: Rana lessonae, R. ridibunda, and R. esculenta. The study included
      premetamorphic larvae (Gosner Stage 40) to frogs that were 5 years old. Femora,
      metatarsal bones, and proximal phalanges of the hindlimb exhibit the same pattern
      of periosteal bone differentiation and the same pattern of growth. Longitudinal
      and radial growth of these bones was studied by examination of the diaphyses and
      epiphyses, particularly where the edge of periosteal bone is inserted into the
      epiphysis. The periosteum seems to be responsible for both longitudinal and
      radial growth. Investigation of the formation, length, and arrangement of lines
      of arrested growth reveals that the first line is present only in the middle 25
      35% of the length of the diaphysis of an adult bone; therefore, only the central
      portion of the diaphysis should be used for age estimation in
      skeletochronological studies. Comparison of the shapes and histological
      structures of epiphyses in the femur, metatarsal bones, and phalanges revealed
      that epiphyseal cartilages are composed of an inner and outer part. The inner
      metaphyseal cartilage has distinct zones and plugs the end of the periosteal bone
      cylinder; its role in longitudinal growth is questioned. The outer epiphyseal
      cartilage is composed of articular cartilages proper, in addition to lateral
      articular cartilages. Differences in the symmetry of the lateral articular
      cartilages of distal epiphyses of the femur and toes may reflect adaptations to
      different kinds of movements at the knee and in the foot.

PMID- 16086407
TI  - Fetus with interstitial del(5)(p13.1p14.2) diagnosed postnatally with Cornelia de
      Lange syndrome.

PMID- 16086408
TI  - p53 Pathway dysfunction in primary childhood ependymomas.
AB  - BACKGROUND: Childhood ependymoma remains a major therapeutic challenge despite
      surgery, chemotherapy, and irradiation. We hypothesized that p53 function might
      be abrogated in ependymomas and implicated in their resistance to anti-cancer
      therapy. PROCEDURE: Primary ependymomas at diagnosis or relapse from 24 children
      were analyzed for p53 pathway, using a functional assay in yeast, RT-PCR, Western
      blot analysis, and/or immunohistochemistry for TP53 mutation, p14(ARF) deletion
      and promoter hypermethylation, MDM2 and PAX5 expression, respectively. p53
      mediated response to radiation-induced DNA damage was evaluated using Western
      blot and flow cytometry analysis in two ependymoma xenograft models, IGREP37 and
      IGREP83, derived from primary anaplastic childhood ependymomas. RESULTS: No TP53,
      MDM2, p14(ARF), PAX5 gene abnormalities were detected in the primary ependymomas
      tumors and xenografts tested. Interestingly, despite the lack of these
      abnormalities, p53 induced p21-mediated G(1) growth arrest in response to
      irradiation was altered in the IGREP37 xenograft tumors. Although irradiation
      induced necrosis and apoptotic cell death, IGREP37 tumors were moderately
      sensitive to radiation therapy in vivo. In contrast, irradiation yielded
      significant tumor growth delays and tumor regressions in the p53 functional
      IGREP83 xenografts. CONCLUSION: Alterations in p53-mediated growth arrest in
      ependymomas might be implicated in the radio-resistance of these tumors and
      demand further evaluation.

PMID- 16086409
TI  - Atypical teratoid rhabdoid tumor in a child with neurofibromatosis 1.

PMID- 16086410
TI  - Toxicity profile of delayed high dose sodium thiosulfate in children treated with
      carboplatin in conjunction with blood-brain-barrier disruption.
AB  - PURPOSE: To assess the safety of delayed high dose intravenous (i.v.) sodium
      thiosulfate (STS) in a case series of 12 children with malignant brain tumors who
      were treated with intraarterial (i.a.) carboplatin in conjunction with blood
      brain-barrier disruption (BBBD). METHODS: Twelve children ages 17 months-12 years
      underwent a total of 132 BBBD chemotherapy treatments and also received delayed
      high dose STS (i.v.). Dose 1 of STS (10-16 g/m(2)) was administered 2 or 4 hr
      after carboplatin, and a second STS dose was administered 4 hr after dose 1 if
      the child had impaired baseline hearing. Toxicity data were graded in accordance
      with the National Cancer Institute Common Toxicity Criteria (Version 2).
      Audiologic monitoring to evaluate the otoprotective potential of STS was
      performed on 11 children. Ototoxicity was defined in accordance with the American
      Speech-Language-Hearing Association (ASHA) criteria. Baseline and end of
      treatment hearing status were graded using Brock's criteria. RESULTS: Nausea and
      vomiting were well controlled with anti-emetics administered approximately 30 min
      prior to STS infusion. Analogous to results in adult patients, there was mild
      transient hypernatremia and a trend for improved protection from ototoxicity in
      children who received STS delayed to 4 hr post-treatment versus 2 hr. Tumor
      responses were seen in heavily pre-treated patients with relatively chemo
      resistant tumors, suggesting that STS did not protect the tumor from platinum
      cytotoxicity. CONCLUSION: High dose STS is well tolerated in children under 12
      years of age. Further studies of STS in children are warranted to assess
      otoprotection and the impact of STS on platinum mediated efficacy.

PMID- 16086411
TI  - Multidisciplinary management of head and neck sarcomas.
AB  - BACKGROUND: Head and neck sarcomas are extremely rare. This article reviews the
      management and outcomes in a multidisciplinary clinic. METHODS: The records of 41
      male and 19 female patients (mean age, 50 years) were reviewed. Forty percent
      underwent surgical resection only, 35% underwent surgery and adjuvant therapy,
      and 25% underwent radiotherapy and/or chemotherapy without surgery. Seventy-one
      percent had complete histologic clearance. RESULTS: The mean follow-up was 3
      years and 10 months, with an overall 5-year survival rate of 60%. Completeness of
      surgical excision was highly significant in determining 5-year local control (p <
      .025), and the addition of adjuvant radiotherapy had a major effect on local
      control, but only if complete surgical clearance had been achieved (p < .025). As
      expected, patients with more aggressive tumors had a significantly poorer overall
      prognosis, and achieving local control led to an enhanced 5-year survival (p <
      .025). CONCLUSION: These tumors are best managed in multidisciplinary clinics,
      and the mainstay of treatment is wide local excision and planned postoperative
      adjuvant radiotherapy.

PMID- 16086412
TI  - Presence of a tracheotomy tube and aspiration status in early, postsurgical head
      and neck cancer patients.
AB  - BACKGROUND: We sought to investigate the effects, if any, that the presence of a
      tracheotomy tube has on aspiration status in early, postsurgical head and neck
      cancer patients. METHODS: Twenty-two consecutive adult, postoperative head and
      neck cancer patients were prospectively evaluated with fiberoptic endoscopic
      evaluation of swallowing (FEES) under three conditions: (1) tracheotomy tube
      present, (2) tracheotomy tube removed and tracheostoma covered with gauze sponge;
      and (3) tracheotomy tube removed and tracheostoma left open and uncovered. For
      each condition, the endoscope was first inserted transnasally to determine
      aspiration status during FEES and then inserted through the tracheostoma to
      corroborate aspiration status by examining the distal trachea inferiorly to the
      carina. Three experienced examiners determined aspiration status under each
      condition and endoscope placement. RESULTS: There was 100% agreement on
      aspiration status between FEES results and endoscopic examination through the
      tracheostoma. Specifically, 13 of 22 patients (59%) swallowed successfully and
      nine of 22 (41%) aspirated. There was also 100% agreement on aspiration status
      for tracheotomy tube present, decannulation and tracheostoma covered by gauze
      sponge, and decannulation and tracheostoma left open and uncovered. CONCLUSIONS:
      Neither presence of a tracheotomy tube nor decannulation affected aspiration
      status in early, postsurgical head and neck cancer patients. The clinical
      impressions that a tracheotomy or tracheotomy tube increases aspiration risk or
      that decannulation results in improved swallowing function are not supported.
      Rather, need for a tracheotomy indicates comorbidities (eg, respiratory failure,
      trauma, stroke, advanced age, reduced functional reserve, and medications used to
      treat the critically ill) that by themselves predispose patients for dysphagia
      and aspiration.

PMID- 16086413
TI  - Neoadjuvant chemotherapy for squamous cell carcinoma of the oral tongue in young
      adults: a case series.
AB  - BACKGROUND: Squamous cell carcinoma of the oral tongue (SCCOT) in the young
      population has emerged as a growing worldwide health problem. Standard therapies,
      consisting primarily of surgery with possible adjuvant radiotherapy, have
      resulted in only modest improvements in survival in recent decades, whereas the
      treatments for SCCOT continue to impair oral function. With the increased use and
      improved functional results of neoadjuvant chemotherapy in the treatment of
      squamous cell carcinoma of other upper aerodigestive tract sites, we have
      reviewed our experience with neoadjuvant chemotherapy in young patients with
      SCCOT. METHODS: A retrospective review was conducted of all patients younger than
      45 years (N = 49) with previously untreated SCCOT evaluated at a comprehensive
      cancer center from July 1995 to August 2001. Charts were reviewed to obtain
      demographic data, comorbidities, nutritional status, tumor status, treatment and
      response information, and follow-up data. RESULTS: Fifteen patients were
      identified who received neoadjuvant chemotherapy with taxane-based regimens
      before undergoing glossectomy and neck dissection. Thirteen of these patients
      (87%) exhibited stage III or IV disease at presentation, and all exhibited at
      least a partial response at the primary site. Pathologically positive nodes were
      identified in only six patients (40%), although 13 (87%) had clinically or
      radiographically suspicious nodes at presentation. Adjuvant radiation therapy was
      administered to seven patients (47%). With a median follow-up of 39 months, no
      patient has had local or regional recurrence, although three patients (20%) have
      had distant metastases develop; one patient with an isolated distant metastasis
      was successfully salvaged with radiation. By comparison during the same period,
      34 young adult patients with SCCOT were treated with surgery with or without
      postoperative radiotherapy but without the use of chemotherapy. Although these
      patients had lower T classifications (18% vs 67% T3/T4; p = .0007), incidence of
      nodal metastases (15% vs 87% N+; p < .0001), and overall disease stage (24% vs
      87% stage III/IV; p < .0001) than the neoadjuvant chemotherapy group, the overall
      survival (82%), disease-specific survival (88%), and recurrence-free survival
      (82%) of the surgery-first group was similar to that of the neoadjuvant
      chemotherapy group (87%, 87%, and 80%, respectively). CONCLUSIONS: This
      retrospective investigation demonstrates that neoadjuvant chemotherapy with
      taxane-based regimens may play a role in the successful treatment of SCCOT in
      young adult patients. Ultimately, this treatment plan may lead to improved
      functional outcomes in young patients with SCCOT by allowing function-sparing
      surgery and avoiding postoperative radiotherapy, without sacrificing disease
      control and survival, but a prospective trial is needed. We have initiated a
      prospective clinical trial to further investigate the impact of neoadjuvant
      chemotherapy in patients younger than 50 with SCCOT.

PMID- 16086414
TI  - Swallow physiology in patients with trach cuff inflated or deflated: a
      retrospective study.
AB  - BACKGROUND: Past research has suggested that medical diagnosis and trach cuff
      conditions may contribute to swallow physiology changes in patients with
      tracheostomy. This study attempts to investigate the differences in swallow
      physiology between patients with trach cuff-inflated and trach cuff-deflated
      conditions with respect to four medical diagnostic categories: neuromuscular
      disorder, head and neck cancer, respiratory diseases, and general medical
      diagnosis. METHODS: Retrospective database analysis of videofluoroscopic study
      results in 623 patients with tracheostomies with trach cuff-inflated or cuff
      deflated conditions. Swallow disorders were examined for each patient. RESULTS:
      The frequencies of reduced laryngeal elevation and silent aspiration were found
      to be significantly higher in the cuff-inflated condition than the cuff-deflated
      condition. Significant swallow physiology changes were also found to be
      significantly different among various medical diagnostic categories. CONCLUSIONS:
      It is important to evaluate changes in swallow physiology under both the trach
      cuff-inflated and cuff-deflated conditions to fully assess swallow function.

PMID- 16086415
TI  - Prognostic indicators for survival in head and neck squamous cell carcinomas:
      analysis of a series of 621 cases.
AB  - BACKGROUND: We sought to study the influence of pT classification, pN status,
      tumor volume, and number of lymph nodes invaded on survival of patients with head
      and neck cancers to improve therapeutic indications. METHODS: This was a
      retrospective study of 621 consecutive patients treated from 1990 to 1997 by a
      single team. RESULTS: In univariate analysis, pT classification (p < .0001), pN
      status (p < .0001), capsule rupture (p < .0001), the number of lymph nodes
      invaded (0, 1-3, 4-9, > or =10) (p < .0001), and the tumor volume (p < .0001)
      were significantly associated with overall survival. A Cox model identified as
      independent prognostic indicators age (p < .0001), pT classification (p < .0001),
      and pN status (p < .0001). CONCLUSIONS: Not only pT classification and pN status
      but also the number of the lymph nodes invaded and the tumor volume should be
      considered as essential prognostic indicators, and any clinical trial developed
      should stratify accordingly.

PMID- 16086416
TI  - ALK-positive plasmablastic B-cell lymphoma with the clathrin-ALK gene
      rearrangement.

PMID- 16086417
TI  - Solitary bone plasmocytoma of the spine in an adolescent.
AB  - Solitary plasmocytoma (SP) represent only about 5% of plasma cell neoplasia. Most
      patients have generalized disease, that is, multiple myeloma (MM). Solitary bone
      plasmocytoma (SBP) is a localized plasma cell tumor and is a very rare disease in
      young patients. We reported here, a case of SPB in a 14-year-old girl with a 10
      year disease-free survival after an aggressive treatment. The relationship of SBP
      to MM continues to be controversial. Recommendations on the diagnosis and
      management of SBP in adults, based on a literature search and consensus of expert
      opinion, were recently published on behalf of the Guidelines Working Group of the
      United Kingdom Myeloma Forum 1. MRI of the spine is necessary to assess local
      disease. Radiotherapy with doses of 45-50 Gy is the recommended treatment and
      gives a high rate of local control (83-96%). Chemotherapy remains controversial
      in contrast to MM, in which intensive chemotherapy with autologous bone marrow
      transplantation (ABMT) is widely accepted. At the present time, considering the
      good prognosis of patients with a normal MRI at diagnosis and a complete
      disappearance of the M protein after radiotherapy, we believe that ABMT should be
      reserved for relapse or primary therapeutic failure.

PMID- 16086418
TI  - Cell sheet detachment affects the extracellular matrix: a surface science study
      comparing thermal liftoff, enzymatic, and mechanical methods.
AB  - This work compares the removal of bovine aortic endothelial cell (BAEC)
      monolayers via 1) low-temperature liftoff from a "smart polymer," plasma
      polymerized poly(N-isopropyl acrylamide) (ppNIPAM), 2) enzymatic digestion, and
      3) mechanical dissociation from ppNIPAM surfaces. We examine the surfaces after
      cell removal by using X-ray photoelectron spectroscopy (XPS), time-of-flight
      secondary ion mass spectrometry (ToF-SIMS), immunostaining, and cell adhesion
      assay. Immunoassay results indicate that low-temperature liftoff nondestructively
      harvests the cell sheet and most of the underlying extracellular matrix (ECM),
      whereas enzymatic digestion and mechanical dissociation are damaging to both the
      cells and ECM. XPS results indicate that amide and alcohol groups attributed to
      proteins in the ECM are present on postliftoff surfaces. Principal component
      analysis (PCA) of ToF-SIMS data indicates that molecular ion fragments of amino
      acids are present on postliftoff surfaces. Finally, a cell adhesion assay seeding
      new cells on surfaces from which an initial layer of cells was removed via each
      of the three methods indicates that liftoff and mechanical dissociation leave
      behind surfaces that better promote cell adhesion. We conclude that the removal
      of BAEC cells via low-temperature liftoff from ppNIPAM-treated surfaces is less
      damaging to the ECM proteins remaining at the surface than the other methods.

PMID- 16086419
TI  - Surface modification of gold and quantum dot nanoparticles with chitosan for
      bioapplications.
AB  - Gold (Au) and quantum dot (QD) nanoparticles, which have been extensively used in
      many fields, were encapsulated with a natural polymer, chitosan, to improve their
      biocompatibility. Characterization was performed using ultraviolet-visible,
      dynamic light scattering, atomic force microscopy, and transmission electron
      microscope analyses. It was found that a Au/chitosan ratio of 1:1 and smaller
      produced chitosan-encapsulated Au nanoparticles of a sufficiently small size, and
      this result was then applied in the chitosan encapsulation of QDs. The
      biocompatibility of both types of nanoparticles was assessed in cell culture
      studies using HT29 human colon carcinoma and NIH 3T3 mouse fibroblast cells. MTT
      and trypan blue exclusion assays revealed that both chitosan-encapsulated Au
      nanoparticles and QDs exhibited improved biocompatibility over their bare,
      nonencapsulated counterparts. Therefore, this study showed that chitosan could be
      used to encapsulate both Au nanoparticles and QDs in order to enhance their
      biocompatibility. The approaches developed in this study can also be extended to
      other nanoparticles for bioapplications as well.

PMID- 16086420
TI  - Pulmonary function in long-term survivors of pediatric hematopoietic cell
      transplantation.
AB  - BACKGROUND: The purpose of this study was to determine the prevalence of
      pulmonary dysfunction in pediatric hematopoietic cell transplant (HCT) survivors
      and to identify associated risk factors. PROCEDURE: In a cross-sectional study,
      patients surviving at least 5 years after pediatric HCT were requested to undergo
      pulmonary function testing (PFT). Risk factors for restrictive lung disease (RLD)
      and obstructive lung disease (OLD) were analyzed using multivariate analysis.
      RESULTS: Among 472 patients contacted, 260 (55%) participated and 215 were
      selected for analysis. These patients were transplanted at a median age of 8.3
      (0.3-18.0) years; 175 for hematologic malignancies and 40 for non-malignant
      diseases. The preparative regimens for 133 patients included fractionated TBI
      (FTBI), 29 single-fraction TBI (SFTBI), and 53 non-TBI regimens. PFT was
      performed at a median of 10 (5.0-27.5) years after HCT. Forty percent of patients
      had either RLD or OLD (28% RLD, 9% OLD, 3% mixed RLD/OLD) and at least 15% had an
      isolated low-DLCO. Moderate-to-severe impairment was present in 45% of patients
      with RLD or OLD. In multivariate analysis, risk factors associated with RLD
      included transplant regimen, transplant diagnosis, scleroderma/contracture, and
      donor relation. Patients treated with SFTBI had the highest risk of RLD. Risk
      factors for OLD included chronic graft-versus-host disease, transplant regimen,
      and time after HCT. Patients surviving 20 or more years after HCT had the highest
      risk of OLD. CONCLUSIONS: Fifty-five percent of long-term pediatric HCT survivors
      had pulmonary dysfunction. These findings stress the need for long-term follow-up
      to detect pulmonary dysfunction.

PMID- 16086421
TI  - How low is too low? Use of cluster analysis to define low levels of
      mercaptopurine metabolites.
AB  - BACKGROUND: To group patients receiving treatment for acute lymphoblastic
      leukemia (ALL) according to their oral mercaptopurine (6-MP) metabolite levels
      and to establish cut-off points to screen for potential poor clinical outcome.
      PROCEDURE: Methodological study using 6-MP metabolite levels from 48 adolescent
      ALL patients enrolled in a multicenter adherence study. Cluster analysis was the
      primary analytical technique. We used two validation methods (a split-sampling
      and a simulation technique) for validating the results. RESULTS: Four clusters
      were retained in our initial analysis using our first group of patients (n = 27).
      Three clusters (labeled 1, 2, and 4) exhibited the expected negative correlation
      between the two metabolites, that is, "high" values of one were associated with
      "low" values of the other. One cluster (labeled 3) had "low" levels for both TGN
      and MMP. Five of the 27 adolescents had their 6-MP "held" during the study. Post
      hoc examination of the results revealed that all five grouped in Cluster 3 during
      the time that their medications were stopped, but grouped in other clusters at
      other times. The median ANC was highest in Cluster 3, consistent with low
      therapeutic drug levels. Parameters were reproducible with both validation
      methods. Values below the respective 75th centile for both TGN and MMP in Cluster
      3 for the complete sample (n = 48) are suggested as representing a potentially
      higher risk for relapse. CONCLUSIONS: This study provides an objective method for
      identifying patients at risk for treatment failure due to suboptimal 6-MP
      therapy; the clinical significance of this approach should be examined in future
      studies.

PMID- 16086422
TI  - Childhood ITP: 12 months follow-up data from the prospective registry I of the
      Intercontinental Childhood ITP Study Group (ICIS).
AB  - BACKGROUND: Acute and chronic idiopathic thrombocytopenic purpura (ITP) is
      traditionally based on the duration of thrombocytopenia at the cut-off point of 6
      months after diagnosis. Registry I evaluated the diagnosis, definition,
      management, and follow-up of childhood ITP. This report focuses on children with
      thrombocytopenia persisting more than 6 months. PROCEDURE: Data were collected by
      questionnaires to the physicians caring for children with ITP, at diagnosis, 6,
      and 12 months later. Data were compared regarding initial features and follow-up
      with emphasis on children with persistent thrombocytopenia, and those with ITP
      who recovered their platelet counts between 7 and 12 months from diagnosis.
      RESULTS: At 12 months from diagnosis, 79 of 308 (25.6%) evaluable children
      recovered from ITP and 229 had ongoing ITP. Children with recovered ITP were
      younger than children with ongoing ITP (P = 0.043) and exhibited a lower
      frequency of bleeding symptoms during the first 6 months after diagnosis (P =
      0.018). Frequency of hospitalization, bone marrow aspiration, and drug treatment
      differed regionally. CONCLUSIONS: The high rate of recovery from ITP between 7 to
      12 months demonstrates, that the cut-off point of 6 months for the definition of
      chronic ITP does not adequately differentiate chronic from acute ITP. The
      majority of children with ITP have variable time to recovery with gradual
      improvement of platelet counts and disappearance of bleeding signs. ITP is a
      heterogeneous disorder with a diverse natural history and diverse pattern of
      treatment response.

PMID- 16086423
TI  - Cancer in adolescents and young adults aged 15-24 years: a report from the North
      of England young person's malignant disease registry, UK.
AB  - BACKGROUND: Descriptions of population-based data have rarely been published
      specifically for adolescents and young adults with cancer. PROCEDURE: Data on
      young adults (15-24 years) diagnosed with cancer in the North of England from
      1968 to 1997 were obtained from the Northern Region Young Person's Malignant
      Disease Registry. Temporal changes in incidence and survival rates were
      investigated. RESULTS: There were 2,329 first cancers diagnosed over the study
      period (M:F 1.22:1). Overall age standardized incidence was 174 cases per million
      15-24 years old, per year, 190 for males and 157 for females. The most common
      cancers in young adults were Hodgkin disease (19%), carcinomas (15%), central
      nervous system tumors (14%), germ cell tumors (13%), and leukemia (11%).
      Comparing incidence for 1968-1977 with 1988-1997 there were significant increases
      in the incidence of bone tumors (rate ratio 1.72, 95% CI 1.10-2.68), testicular
      tumors (rate ratio 1.64, 95% CI 1.16-2.32), thyroid cancer (rate ratio 2.63, 95%
      CI 1.37-5.02), and malignant melanoma (rate ratio 2.04, 95% CI 1.36-3.08).
      Survival rates improved significantly (P < 0.001) over the study period; 5-year
      survival rates over the three time periods 1968-1977, 1978-1987, 1988-1997 for
      all cancers were 45% (95% CI 41%-49%), 62% (95% CI 58%-65%), and 74% (95% CI 71%
      77%) respectively. CONCLUSIONS: Survival rates improved and there were
      significant increases in incidence for specific cancers in young adults in the
      North of England. Further research is required to identify the reasons for
      changing incidence and to investigate the late effects of treatment among
      survivors.

PMID- 16086424
TI  - Identification of a 2-cM minimal deletion at 6q16.3-21 in childhood acute
      lymphoblastic leukemia in China.

PMID- 16086425
TI  - Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma.
AB  - BACKGROUND: Survivors of Hodgkin lymphoma and other patients who receive neck
      irradiation are at increased risk of thyroid cancer. Ultrasonography provides an
      inexpensive and non-invasive method of thyroid screening, but the clinical
      significance of thyroid nodules detected by ultrasound screening is uncertain.
      PROCEDURE: We reviewed the demographics, clinical characteristics, method of
      detection, and outcome of patients who developed thyroid nodules after treatment
      for pediatric Hodgkin lymphoma at our institution. One radiologist reviewed all
      imaging studies. RESULTS: Sixty-seven children treated for Hodgkin lymphoma from
      1962 to 2001 developed thyroid nodules. The study group represented 9,024 person
      years of follow-up after the diagnosis of Hodgkin lymphoma and 581 person-years
      after diagnosis of a thyroid nodule. A median of 10.5 years (range, 0.2-24.8
      years) elapsed between the diagnoses of Hodgkin lymphoma and thyroid nodule(s).
      All but one patient had received neck irradiation for Hodgkin lymphoma, with a
      median thyroid radiation dose of 35 Gy (range, 12-45 Gy). Thyroid nodules were
      found to be malignant in seven patients (10%), at a median of 16.2 years (range,
      8.4-23.7 years) after diagnosis of Hodgkin lymphoma. Only one malignancy was
      found through screening ultrasonography. All patients with thyroid cancer
      remained disease-free at 0.4-16.2 years of follow-up. CONCLUSIONS: Thyroid
      nodules are common in Hodgkin lymphoma survivors treated with neck irradiation,
      but the majority of these lesions have an indolent clinical course and do not
      undergo malignant transformation. Only patients with a palpable mass or clinical
      symptoms need more extensive evaluation, including Doppler-flow ultrasonography
      and fine-needle aspiration.

PMID- 16086426
TI  - Post-transplant multiple myeloma in a pediatric renal transplant patient.
AB  - Post-transplant lymphoproliferative disease (PTLD) is a well-recognized
      complication of the intense immunosuppression required in solid organ and bone
      marrow transplant recipients. The clinical presentation is varied and can range
      from a benign infectious mononucleosis-like syndrome to malignant lymphoma. PTLD
      manifesting as multiple myeloma occurs rarely. We report the unique occurrence of
      Epstein-Barr virus (EBV)-associated post-transplant multiple myeloma in a 16-year
      old male. In contrast to previously described cases of PTLD-myeloma type, this
      patient was very young, had a clear association with EBV, and an indolent
      clinical course.

PMID- 16086427
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy with tumefactive
      central demyelination.
AB  - A 46-year-old man with a 1-year history of distal paresthesias and mild distal
      weakness subacutely developed paralysis of the left hand. Electrodiagnostic
      evaluation revealed a demyelinating peripheral neuropathy that met criteria for
      chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Magnetic
      resonance imaging of the brain revealed a mass that enhanced with contrast, but
      revealed focal myelin loss with intense macrophage activity and axonal
      preservation on biopsy. The mass and hand weakness improved following steroid
      therapy. The combination of CIDP and central demyelination with mass effect
      broadens the spectrum of demyelinating disease in association with CIDP.

PMID- 16086428
TI  - Dysregulation of memory-related proteins in the hippocampus of aged rats and
      their relation with cognitive impairment.
AB  - In the present experiments, we used conditioned fear to study whether changes in
      expression or functional state of proteins known to be involved in hippocampal
      learning could suggest correlation with age-related memory deficits. We focused
      on both alterations constitutively present in the hippocampus of aged rats and
      alterations related to different learning responses. Our results point at the
      dysregulation of the phosphorylation state of CREB in the hippocampus of aged
      rats as a primary biochemical correlate of their impaired memory. Other proteins,
      known to be important for various steps of memory formation and consolidation and
      linked to CREB, are to some extent altered in their constitutive expression or in
      the response to learning in the aged hippocampus. In particular, phosphorylated
      CREB and Arc, a protein functionally related to CREB in memory consolidation, are
      both present at constitutively higher levels in the hippocampus of aged rats, but
      they are not susceptible to the learning-related up-regulation occurring in young
      adults. Two other CREB-regulated proteins involved in memory consolidation, the
      neurotrophin BDNF and the transcription factor C/EBPbeta, are expressed at
      similar levels in the hippocampus of young-adult and aged rats, but their
      response to conditioned fear learning appears dysregulated by aging. Calcineurin,
      a protein phosphatase having CREB among its substrates and whose expression
      negatively correlates with learning, is more expressed in the hippocampus of aged
      rats. However, while calcineurin expression decreases in the hippocampus of young
      adults after learning, no changes are observed in the hippocampus of aged,
      learning-impaired rats.

PMID- 16086429
TI  - Competitive interactions between endogenous LTD and LTP in the hippocampus
      underlie the storage of emotional memories and stress-induced amnesia.
AB  - This speculative review serves two purposes. First, it as an extension of the
      ideas we developed in a previous review (Diamond et al., Hippocampus, 2004;14:281
      291), and second, it is a rebuttal to Abraham's (Hippocampus, 2004;14:675-676)
      critique of that review. We had speculated on the functional significance of the
      finding that post-training LTP induction produces retrograde amnesia. We noted
      the similarities between the findings that strong tetanizing stimulation can
      produce LTP and retrograde amnesia, and that a strong emotional experience can
      produce a long-lasting memory and retrograde amnesia, as well. The commonalities
      between LTP induction and emotional learning provided the basis of our hypothesis
      that an emotional experience generates endogenous LTD/depotentiation, which
      reverses synaptic plasticity formed during previous learning experiences, and
      endogenous LTP, which underlies the storage of new information. Abraham raised
      several concerns with our review, including the criticism that our speculation
      "falters because there is no evidence that stress causes LTD or depotentiation,"
      and that research on stress and hippocampus has "failed to report any LTP-like
      changes." Abraham's points are well-taken because stress, in isolation, does not
      appear to generate long-lasting changes in baseline measures of hippocampal
      excitability. Here, within the context of a reply to Abraham's critique, we have
      provided a review of the literature on the influence of stress, novelty, fear
      conditioning, and the retrieval of emotional memories on cognitive and
      physiological measures of hippocampal functioning. An emphasis of this review is
      our hypothesis that endogenous forms of depotentiation, LTD and LTP are generated
      only when arousing experiences occur in conjunction with memory-related
      activation of the hippocampus and amygdala. We conclude with speculation that
      interactions among the different forms of endogenous plasticity underlie a form
      of competition by synapses and memories for access to retrieval resources.

PMID- 16086430
TI  - Late coil displacement after interventional closure of a perimembranous
      ventricular septal defect: a case report.
AB  - Muscular and perimembranous ventricular septal defects can be closed with nitinol
      plugs or spiral coils. Displacement and embolization of the device are well known
      complications that usually occur during or early after the procedure. We present
      the case of a 12-year-old boy with asymptomatic coil displacement detected at a
      routine examination 5 months after closure of a perimembranous ventricular septal
      defect.

PMID- 16086431
TI  - Design-based stereological analysis of the lung parenchymal architecture and
      alveolar type II cells in surfactant protein A and D double deficient mice.
AB  - Alveolar epithelial type II cells synthesize and secrete surfactant. The
      surfactant-associated proteins A and D (SP-A and SP-D), members of the collectin
      protein family, participate in pulmonary immune defense, modulation of
      inflammation, and surfactant metabolism. Both proteins are known to have
      overlapping as well as distinct functions. The present study provides a design
      based stereological analysis of adult mice deficient in both SP-A and SP-D (A(
      )D(-)) with special emphasis on parameters characterizing alveolar architecture
      and surfactant-producing type II cells. Compared to wild-type, A(-)D(-) mice have
      fewer and larger alveoli, an increase in the number and size of type II cells, as
      well as more numerous and larger alveolar macrophages. More surfactant-storing
      lamellar bodies are seen in type II cells, leading to a threefold increase in the
      total volume of lamellar bodies per lung, but the mean volume of a single
      lamellar body remains constant. These results demonstrate that chronic deficiency
      of SP-A and SP-D in mice leads to parenchymal remodeling, type II cell
      hyperplasia and hypertrophy, and disturbed intracellular surfactant metabolism.
      The design-based stereological approach presented here provides a framework for
      the quantitative lung structure analysis in gene-manipulated mice as well as in
      human lung disease.

PMID- 16086432
TI  - Vitamin A storage in hepatic stellate cells in the regenerating rat liver: with
      special reference to zonal heterogeneity.
AB  - Under physiological conditions, hepatic stellate cells (HSCs) within liver
      lobules store about 80% of the total body vitamin A in lipid droplets in their
      cytoplasm, and these cells show zonal heterogeneity in terms of vitamin A-storing
      capacity. Vitamin A is essential for the growth and differentiation of cells, and
      it is well known that liver cells including HSCs show a remarkable growth
      capacity after partial hepatectomy (PHx). However, the status of vitamin A
      storage in HSCs in the liver regeneration is not yet known. Therefore, we
      conducted the present study to examine vitamin A storage in these cells during
      liver regeneration. Morphometry at the electron microscopic level, fluorescence
      microscopy for vitamin A autofluorescence, and immunofluorescence microscopy for
      desmin and alpha-smooth muscle actin (alpha-SMA) were performed on sections of
      liver from male Wistar strain rats at various times after the animal had been
      subjected to 70% PHx. The mean area of vitamin A-storing lipid droplets per HSC
      gradually decreased toward 3 days after PHx, and then returned to normal within
      14 days after it. However, the heterogeneity of vitamin A-storing lipid droplet
      area per HSC within the hepatic lobule disappeared after PHx and did not return
      to normal by 14 days thereafter, even though the liver volume had returned to
      normal. These results suggest that HSCs alter their vitamin A-storing capacity
      during liver regeneration and that the recovery of vitamin A homeostasis requires
      a much longer time than that for liver volume.

PMID- 16086433
TI  - Adult and developmental myosin heavy chain isoforms in soleus muscle of aging
      Fischer Brown Norway rat.
AB  - Fiber type shifts in aging skeletal muscle have been studied with myofibrillar
      ATPase histochemistry and gel electrophoresis, but less commonly with
      immunohistochemistry. Immunohistochemical study of myosin heavy chains (MHCs) in
      single myofibers yields additional information about aged skeletal muscle.
      Furthermore, many studies of aging rodent skeletal muscle have been performed on
      fast-MHC-predominant muscle and in several different strains. The aim of this
      study was to evaluate immunohistochemically MHC characteristics in the slow-MHC
      predominant soleus muscle in the Fischer Brown Norway F1 hybrid aging rat (FBN).
      Three age groups of FBN rats were studied: 12 months, 30 months, and 36 months.
      Soleus muscles were excised, quick-frozen, and stained immunohistochemically for
      slow, fast, developmental, and neonatal MHC isoforms. Cross-sections were
      evaluated for the number and cross-sectional areas of fibers expressing each
      isoform. Single myofibers in soleus muscles of the aged rats showed significantly
      greater amounts of coexpression of slow and fast MHC than did younger animals.
      This change began by 30 months of age, but did not reach statistical significance
      until 36 months of age. The soleus from 36-month-old rats also expressed greater
      amounts of developmental MHC than did the other groups. These developmental MHC
      positive myofibers also coexpressed either slow or slow and fast MHC. The age
      related increase in MHC coexpression of slow with fast isoforms may indicate a
      fiber type shift suggestive of denervation that outpaces reinnervation. The
      developmental MHC-positive fibers provide evidence of ongoing myofiber remodeling
      in the oldest rats in the midst of the fiber degeneration of aging.

PMID- 16086434
TI  - Association of increased type I collagen expression and relative stromal
      overgrowth in mouse epididymis neonatally exposed to diethylstilbestrol.
AB  - The aim of this study was to investigate the molecular changes that underlie
      morphological changes in the epididymis following neonatal exposure to potent
      synthetic estrogen, namely diethylstilbestrol (DES). Newborn male mice were
      subcutaneously injected with DES or endogenous estrogen, namely 17 beta-estradiol
      (E2) (5 microg/mouse/day), for the first 5 days. At the age of 2, 4, and 8 weeks,
      epididymides of the mice were dissected. Characteristic morphological
      abnormality, such as relative stromal overgrowth, was observed at the age of 2
      weeks in the epididymis of DES-treated mice, but not in E2-treated mice.
      Microarray and real-time RT-PCR analyses revealed that the expression levels of
      procollagen type I alpha 1 (col1a1) and col1a2 genes were markedly upregulated at
      the age of 2 weeks in the epididymis of DES-treated mice in comparison with the
      control. Western blot analysis revealed that type I collagen protein expression
      level in epididymis of DES-treated mice was elevated at the age of 2 weeks. In
      situ hybridization analysis revealed that the signals of col1a1 mRNA were
      detected similarly throughout the stromal tissue of epididymis at the age of 2
      weeks in control and DES- and E2-treated mice. The gene expression level of
      epididymal type III collagen (col3a1), which is found in many stromal connective
      tissues as well as type I collagen, did not change at the age of 2 weeks in all
      groups. These results suggest that the increased type I collagen expression is
      associated with the relative stromal overgrowth in the epididymis of DES-treated
      mice.

PMID- 16086435
TI  - Image retrieval with principal component analysis for breast cancer diagnosis on
      various ultrasonic systems.
AB  - OBJECTIVES: We present a computer-aided diagnostic (CAD) system with textural
      features and image retrieval strategies for classifying benign and malignant
      breast tumors on various ultrasonic systems. Effective applications of CAD have
      used different types of texture analysis. Nevertheless, most approaches performed
      in a specific ultrasonic machine do not indicate whether the technique functions
      satisfactorily for other ultrasonic systems. This study evaluated a series of
      pathologically proven breast tumors using various ultrasonic systems. METHODS:
      Altogether, 600 ultrasound images of solid breast nodules comprising 230
      malignant and 370 benign tumors were investigated. All ultrasound images were
      acquired from four diverse ultrasonic systems. The suspicious tumor area in the
      ultrasound image was manually chosen as the region-of-interest (ROI) subimage.
      Textural features extracted from the ROI subimage are supported in classifying
      the breast tumor as benign or malignant. However, the textural feature always
      behaves as a high-dimensional vector. In practice, high-dimensional vectors are
      unsatisfactory at differentiating breast tumors. This study applied the principal
      component analysis (PCA) to project the original textural features into a lower
      dimensional principal vector that summarized the original textural information.
      The image retrieval techniques were employed to differentiate breast tumors,
      according to the similarities of the principal vectors. The query ROI subimages
      were identified as malignant or benign tumors according to characteristics of
      retrieved images from the ultrasound image database. RESULTS: Using the proposed
      CAD system, historical cases could be directly added into the database without a
      retraining program. The area under the receiver-operating characteristics curve
      for the system was 0.970+/-0.006. CONCLUSION: The CAD system identified solid
      breast nodules with comparatively high accuracy in the different ultrasound
      systems investigated.

PMID- 16086436
TI  - Multicontrast MRI of remyelination in the central nervous system.
AB  - Although magnetic resonance imaging (MRI) represents the most sensitive tool for
      the detection of white matter abnormalities in patients with multiple sclerosis
      (MS), the heterogeneity of MS placques severely hampers the elucidation of
      specific pathophysiological processes. In order to identify putative MRI markers
      for de- and remyelination, we employed the cuprizone mouse model which leads to a
      selective and reversible demyelination of the corpus callosum with little or no
      axonal damage. Apart from histopathology, animals were studied with high
      resolution three-dimensional MRI in vivo using multiple contrasts. While
      individual MRI findings significantly correlated with electron microscopy, the
      differentiation of regions with normal, demyelinated or remyelinated white matter
      by one contrast alone was less specific than by histology or electron microscopy.
      However, an accurate MRI prediction of the in vivo myelin status was achieved by
      a discriminant function analysis using a combination of T1, T2 and magnetization
      transfer contrast. With a correct assignment of 95% of all animals examined, the
      procedure will allow for the survey of new therapeutic approaches aiming at
      improved remyelination.

PMID- 16086437
TI  - Prenatal diagnosis of del(9)(p24): a sex reverse case.
AB  - BACKGROUND: We report on a fetus with sex reversal and del(9)(p24) consequent to
      a malsegregation of a maternal balanced complex translocation involving
      chromosomes 7, 9 and 11. METHODS: Fluorescence in situ hybridization (FISH) was
      performed in order to verify the presence of the SRY gene and the absence of
      DMRT1 and DMRT2 genes located in 9p24.3 region and frequently associated with sex
      reversal. RESULTS AND CONCLUSIONS: The prenatal karyotype revealed an unbalanced
      male fetus. The postmortem examination showed a malformed fetus with female
      external genitalia. Lack of DMRT1-2 genes established by FISH.

PMID- 16086438
TI  - Expression of NOX1, a superoxide-generating NADPH oxidase, in colon cancer and
      inflammatory bowel disease.
AB  - Reactive oxygen species (ROS) are at the centre of many physiological and
      pathological processes. NOX1, a ROS-producing NADPH oxidase, is highly expressed
      in the colon but its function in colonic physiology or pathology is still poorly
      understood. It has been suggested to play a role in host defence, but also in
      cell growth and possibly malignant transformation. In this study we characterized
      NOX1 expression in human colon samples derived from healthy control subjects and
      patients with colon cancer or inflammatory bowel disease (IBD). NOX1 mRNA
      expression was assessed by dot-blot hybridization, real-time PCR and in situ
      hybridization, using samples derived from surgical specimens from patients
      undergoing colon resection. In normal tissues, NOX1 expression was low in the
      ileum, intermediate in the right colon, and high in the left colon (p = 0.0056
      right vs. left colon). NOX1 mRNA levels were not influenced by factors linked to
      colon tumourigenesis, such as age or sex. Moreover, there was no statistical
      difference in NOX1 expression between samples derived from adenomas, well
      differentiated or poorly differentiated colon adenocarcinomas. At a cellular
      level, NOX1 was highly expressed in colon epithelial cells, both within the
      crypts and on the luminal surface. In addition, a population of lymphocytes,
      particularly in the appendix, showed NOX1 expression. Lymphocytes in lesions of
      Crohn's disease and ulcerative colitis were also strongly positive for NOX1. In
      conclusion, NOX1 is an enzyme that is constitutively expressed in colon
      epithelium and is not associated with tumourigenesis. Its distribution in crypts
      and on the luminal surface, as well as its left-to-right gradient in the colon,
      suggests a role in host defence function. In addition to the known epithelial
      localization, we define lymphocytes as a novel site of NOX1 expression, where it
      may potentially be involved in the pathogenesis of inflammatory bowel diseases.

PMID- 16086441
TI  - Borinium, borenium, and boronium ions: synthesis, reactivity, and applications.
AB  - Boron cations are elusive and highly electrophilic species that play a key role
      in the chemistry of boron. Despite early interest in the chemistry of boron
      cations, until recently they have largely remained chemical curiosities. However,
      hints at harnessing their potential as potent electrophiles have begun to appear
      and developments in weakly coordinating anion technology suggest that this is an
      area of research that is ripe for exploration. It has been nearly 20 years since
      the last major review on boron cations; herein we summarize the progress in the
      area since that time.

PMID- 16086443
TI  - Prediction of pregnancy complications by first-trimester maternal serum PAPP-A
      and free beta-hCG and with second-trimester uterine artery Doppler.
AB  - BACKGROUND: Previous studies have shown an association between low first
      trimester maternal serum free beta-hCG and PAPP-A and subsequent development of
      pregnancy complications. Similarly, uterine artery Doppler in the late second
      trimester has shown that high impedance to flow is associated with increased risk
      for preeclampsia and fetal growth restriction. The objective of this study is to
      determine whether there is an association between the maternal serum
      concentration of PAPP-A and free beta-hCG at 11-13(+6) weeks with the uterine
      artery pulsatility index (PI) at 22-24 weeks, and secondly, to compare the
      screening characteristics of the two methods in the prediction of adverse
      pregnancy outcome. METHODS: Maternal serum PAPP-A and free beta-hCG at 11-13(+6)
      weeks and uterine artery PI at 22-24 weeks were measured in 4390 women with
      singleton pregnancies. Pregnancies with chromosomal defects or fetal anomalies
      were excluded. The biochemical and Doppler measurements were compared between
      those with normal outcome and those resulting in spontaneous preterm delivery,
      pre-eclampsia and fetal growth restriction (FGR). Detection rates using a
      combination of the biochemical and Doppler measurements were investigated.
      RESULTS: In the pregnancies resulting in pre-eclampsia (n = 64) and FGR (n =
      172), the median PAPP-A was lower (0.844 and 0.813 MoM), the median uterine
      artery mean PI was higher (1.56 and 1.18) but the median free betahCG was not
      significantly different (0.923 and 0.933 MoM) than in the normal outcome group.
      In the preterm delivery group (n = 159), the median free beta-hCG (0.944 MoM) and
      uterine artery mean PI (1.06) were not significantly different from normal but
      the median PAPP-A (0.928 MoM) was significantly lower than normal. In screening
      for pre-eclampsia, the detection rate, for a 5% false-positive rate, was 14.1%
      for PAPP-A, 54.7% for uterine artery mean PI and 62.1% for a combination of PAPP
      A and uterine artery mean PI. CONCLUSION: Maternal serum PAPP-A at 11-13(+6) of
      gestation is significantly lower in adverse pregnancy outcomes. The combination
      of first trimester serum PAPP-A and uterine artery mean PI at 22-24 weeks
      improves the screening efficacy for the prediction of pre-eclampsia.

PMID- 16086444
TI  - Expression and localization of Reg IV in human neoplastic and non-neoplastic
      tissues: Reg IV expression is associated with intestinal and neuroendocrine
      differentiation in gastric adenocarcinoma.
AB  - Regenerating islet-derived family, member 4 (Reg IV) is a candidate marker for
      cancer and inflammatory bowel disease. In the present study, immunohistochemical
      analysis of Reg IV was performed in various human neoplastic (n = 289) and non
      neoplastic tissues. In the stomach, foveolar epithelium was negative for Reg IV,
      whereas goblet cells of intestinal metaplasia and neuroendocrine cells at the
      base of intestinal metaplasia expressed Reg IV. Neuroendocrine cells of the small
      intestine and colon showed strong expression of Reg IV, whereas goblet cells of
      the small intestine and colon showed weak or no expression of Reg IV. Insulin
      producing beta cells of the endocrine pancreas were positive for Reg IV. Among
      143 gastric adenocarcinomas, Reg IV expression was detected in 42 (29.4%) and was
      associated with both the intestinal mucin phenotype and neuroendocrine
      differentiation. No association was found between Reg IV expression and clinical
      characteristics such as tumour stage and patient prognosis. Of 36 colorectal
      adenocarcinomas, 13 (36.1%) were positive for Reg IV, which was associated with
      tumour stage (p = 0.0379, Fisher's exact test). Expression of Reg IV was detected
      in 14 (93.3%) of 15 colorectal carcinoid tumours. Reg IV expression was also
      detected in 5 (21.7%) of 23 ductal adenocarcinomas of the pancreas. In contrast,
      lung cancers (n = 30) and breast cancers (n = 30) did not express Reg IV. This is
      the first immunohistochemical analysis of the expression and distribution of Reg
      IV protein in human tumours. These data suggest that Reg IV is expressed by
      gastrointestinal and pancreatic tumours, including adenocarcinomas and carcinoid
      tumours, and that Reg IV is associated with intestinal and neuroendocrine
      differentiation of the stomach and gastric carcinoma.

PMID- 16086445
TI  - Chemiluminescence of iron-chlorophyllin.
AB  - The iron-chlorophyllin complex was found to be chemiluminescent (CL) in an
      acetonitrile (22%)/water mixed solvent. In the presence of hydrogen peroxide,
      when iron-chlorophyllin was added to the mixed solvent, a sharp CL signal
      immediately appeared. Also, analysis of the absorption spectra revealed
      decomposition of iron-chlorophyllin (based on decrease in absorbance at 396 nm),
      hence iron-chlorophyllin is the CL substance. Moreover, the CL intensity
      decreased in the presence of potassium thiocyanate (KSCN), indicating that the
      axial coordinative position of iron-chlorophyllin acts as a point of catalytic
      activation. In addition, when fluorophores were present with iron-chlorophyllin
      CL, their CL intensity values were similar to or greater than that of the well
      known trichlorophenylperoxalate ester (TCPO) CL. Thus, during the decomposition
      reaction of iron-chlorophyllin, the latter transfers its energy to the coexisting
      fluorophores. Moreover, since the decomposed compound in this CL reaction had a
      fluorescence, it was found that the iron-chlorophyllin also functions as an
      energy donor. Therefore, the iron-chlorophyllin complex acts not only as a CL
      substance, but also as a catalyst and energy donor in the reaction.

PMID- 16086446
TI  - An individual approach.

PMID- 16086447
TI  - On firm foundations.

PMID- 16086448
TI  - Trends in biomass and metal sequestration associated with reeds and algae at
      Wheal Jane Biorem pilot passive treatment plant.
AB  - An assessment of the rate of biomass production both of the reeds in the aerobic
      cells and the algae in the rock filters, which form the final stage in the series
      of treatment cells, has been undertaken. The biomass production for the reeds was
      found to be highest for the lime-dosed anoxic limestone drain system, but even
      this was very low in comparison to values reported for natural and constructed
      wetlands. The algal coverage of each lagoon was relatively homogeneous, with no
      significant difference between the three systems studied. However, too many
      unknown factors suggest that further study is required. The metal uptake was
      higher in the roots than the stems, although no variation between cells of
      systems was detectable, and the difference was not as marked as reported by other
      workers. The metal concentrations in the debris samples were markedly higher than
      the roots of the reeds. The values for Fe, Al and As were several orders of
      magnitude larger than the influent minewater. Further study is required here, but
      this appears to be a key component in the function of the reeds. The lime-dosed
      system rock filter showed the highest Fe removal rate but the lowest Mn removal
      rate. Some possible mechanisms are discussed in the paper, but further
      investigation would be required to test these hypotheses.

PMID- 16086449
TI  - Hereditary fructose intolerance.

PMID- 16086450
TI  - Risk factors differ according to same-sex and opposite-sex interest.
AB  - Are risk behaviours in adolescence differentiated according to same-sex vs
      opposite-sex interest? For all respondents a five-point scale of interest in each
      sex used information from both of the first two in-home waves of the National
      Longitudinal Study of Adolescent Health (Add Health). Logistic regression
      predicted the probability of experiencing each risk behaviour from the same-sex
      and opposite-sex interest scores. Same-sex interests have more effect on
      emotional risk, and opposite-sex interests have more effect on substance use.
      Nevertheless, all risk variables except boys' depression are responsive to both
      same-sex and opposite-sex interest. The same-sex interest component of risk is
      attributed to the emotional strain of living with an anomalous sex interest in a
      heterosexual society.

PMID- 16086451
TI  - Hexahydro-1,3,5-trinitro-1,3,5-triazine transformation by biologically reduced
      ferrihydrite: evolution of Fe mineralogy, surface area, and reaction rates.
AB  - Microbial respiration of Fe(III) oxides has been shown to produce reduced Fe
      phases that are capable of transforming a variety of oxidized contaminants.
      Little data, however, are available on how these Fe phases evolve over time and
      how this evolution may affect their ability to reduce contaminants. Here,the
      evolution and reactivity of biologically reduced ferrihydrite were monitored over
      a period of 14 months. Solids were collected from a culture of Geobacter
      metallireducens (GS-15) thatwas incubated with ferrihydrite (as the electron
      acceptor) for 0, 7, 10, 20, 75, and 400 days. Mineralogical composition and
      surface area of the biologically reduced solids were characterized using
      Mossbauer spectroscopy, X-ray diffraction, and BET with N2 adsorption. By day 10,
      ferrihydrite began to transform, and a nanoparticle magnetite/maghemite phase, as
      well as two ferrous phases, was observed. One of the ferrous phases was
      identified as siderite, whereas the other could not be positively identified.
      Likely candidates, however, include Fe(OH)2(s) or an adsorbed Fe(II) species.
      Over the next few months, ferrihydrite was completely reduced and evolved into a
      mixture containing about 70% magnetite/maghemite, 19% siderite, and 11% of the
      second Fe(II) phase. The effect of incubation time on the reactivity of the
      biologically reduced solids was evaluated by measuring the kinetics of hexahydro
      1,3,5-trinitro-1,3,5-triazine (RDX) transformation. The only products observed
      were the three reduced nitroso products. Rate coefficients (k) for RDX
      transformation were dramatically influenced by incubation time with half-lives of
      about 1 month observed in the presence of solids incubated for 10 and 20 days, 3
      months with solids incubated for 75 days, and negligible removal with solids
      incubated for 400 days. The loss of reactivity was not directly correlated to any
      one mineralogical variable but may be due to particle size or surface chemistry
      changes in the reactive Fe phase or to cell die-off and the accumulation of cell
      lysis products after consumption of the electron acceptor. The dramatic effect of
      incubation time on the rate of RDX removal highlights a potential limitation of
      studying complex systems, as we have here, in batch reactors and suggests that
      incubation time is an important variable to consider when measuring and comparing
      rates of contaminant reduction.

PMID- 16086452
TI  - Link between chemotactic response to Ni2+ and its adsorption onto the Escherichia
      coli cell surface.
AB  - Bacterial chemotaxis is of medical, biological, and geological significance.
      Despite its importance, current chemotaxis measurements fail to account for the
      speciation of the chemical effector and the protonation state of the bacterial
      surface. We hypothesize that adsorption of Ni2+ onto the surface of Escherichia
      coli can influence its effective concentration and therefore influence its
      ability to induce a repellent response. By measuring repellent response at
      different pH values, the influence of Ni2+ adsorption on chemotaxis was assessed.
      In addition, we tested the effect of different Ni2+ chelating agents. Our data
      indicate that adsorption reactions influence the chemotactic response to Ni2+. We
      use potentiometric titration and Ni2+ adsorption experiments to develop and
      constrain a thermodynamic model capable of quantifying the concentration of Ni2+
      at the bacteria/solution interface. Results from this model predict that the
      concentration of adsorbed Ni2+ is linearly proportional to the magnitude of the
      chemotactic response in E. coli. If adsorption is linked to chemotaxis in other
      cases, then chemotactic responses in realistic settings depend on a number of
      environmental factors such as pH, competing binding agents (e.g., aqueous organic
      acids, natural organic matter, mineral surfaces, etc.), and ionic strength. Our
      modeling approach quantifies adsorbed species on bacterial surfaces and may be
      used to predict the responses of different species to a variety of
      chemoeffectors. Our data suggest that specified changes in environmental
      conditions can be used to tune chemotactic responses in natural biological and
      geological settings.

PMID- 16086453
TI  - Biochemical reaction network modeling: predicting metabolism of organic chemical
      mixtures.
AB  - All organisms are exposed to multiple xenobiotics, through food, environmental
      contamination, and drugs. These xenobiotics often undergo biotransformation, a
      complex process that plays a critical role in xenobiotic elimination or
      bioactivation to toxic metabolites. Here we describe the results of a new
      computer-based simulation tool that predicts metabolites from exposure to
      multiple chemicals and interconnects their metabolic pathways, using four common
      drinking water pollutants (trichloroethylene, perchloroethylene,
      methylchloroform, and chloroform) as a test case. The simulation tool
      interconnected the metabolic pathways for these compounds, predicted reactive
      intermediates, such as epoxides and acid chlorides, and uncovered points in the
      metabolic pathways where typical endogenous compounds, such as glutathione or
      carbon dioxide, are consumed or generated. Moreover, novel metabolites, not
      previously reported, were predicted via this methodology. Metabolite prediction
      is based on a reaction-mechanism-based methodology, which applies fundamental
      organic and enzyme chemistry. The tool can be used to (a) complement experimental
      studies of chemical mixtures, (b) aid in risk assessment, and (c) help understand
      the effects of complex chemical mixtures. Our results indicate that this tool is
      useful for predictive xenobiotic metabolomics, providing new and important
      insights into metabolites and the interrelationship between diverse chemicals
      that hitherto may have remained unnoticed.

PMID- 16086454
TI  - [Chromatin remodeling by RNA polymerase II].
AB  - Tight compaction of eukaryotic DNA in chromatin having several levels of
      organization results in formation of a structure that is barely accessible to
      regulatory protein complexes and enzymes such as DNA-and RNA-polymerases. To deal
      with this intricate chromatin organization, numerous chromatin remodeling
      mechanisms operating at various levels of chromatin structure were developed.
      Recently it has become apparent that numerous intranuclear processes of DNA
      metabolism (such as transcription, repair etc.) are often regulated at the level
      of chromatin remodeling. The mechanisms of chromatin remodeling and its
      regulation are beginning to emerge. Thus the histone octamer has a remarkable
      ability to survive action of various processive enzymes, such as DNA- and RNA
      polymerases, as well as ATP-dependent remodelers. Here we discuss the mechanisms
      of chromatin remodeling during transcription with primary focus on chromatin
      remodeling by transcribing Pol II.

PMID- 16086455
TI  - The dreaded impact factor is back to haunt us!

PMID- 16086456
TI  - Prevention and control of influenza. Recommendations of the Advisory Committee on
      Immunization Practices (ACIP).
AB  - This report updates the 2004 recommendations by the Advisory Committee on
      Immunization Practices (ACIP) regarding the use of influenza vaccine and
      antiviral agents (CDC. Prevention and control of influenza: recommendations of
      the Advisory Committee on Immunization Practices [ACIP]. MMWR 2004;53[No. RR-6]:1
      40). The 2005 recommendations include new or updated information regarding 1)
      vaccination of persons with conditions leading to compromise of the respiratory
      system; 2) vaccination of health-care workers; 3) clarification of the role of
      live, attenuated influenza vaccine (LAIV) in vaccine shortage situations; 4) the
      2005-06 trivalent vaccine virus strains: A/California/7/2004 (H3N2)-like, A/New
      Caledonia/20/99 (H1N1)-like, and B/Shanghai/361/2002-like antigens (for the
      A/California/7/2004 [H3N2]-like antigen, manufacturers may use the antigenically
      equivalent A/New York/55/2004 virus, and for the B/Shanghai/361/2002-like
      antigen, manufacturers may use the antigenically equivalent B/Jilin/20/2003 virus
      or B/Jiangsu/10/2003 virus); and 5) the assessment of vaccine supply, timing of
      influenza vaccination, and prioritization of inactivated vaccine in shortage
      situations. A link to this report and other information can be accessed at
      http://www.cdc.gov/flu.

PMID- 16086457
TI  - Amicus brief: In the matter of Baby M.

PMID- 16086458
TI  - Business ethics, law, and the corporate use of laboratory animals.

PMID- 16086459
TI  - Psychiatric and chemical dependency treatment of minors: the myth of voluntary
      treatment and the capacity to consent.

PMID- 16086460
TI  - Childhood competence and autonomy.

PMID- 16086461
TI  - Two ships passing in the night: an interpretavist review of the White-Stevens
      colloquy on Roe v. Wade.

PMID- 16086462
TI  - Should a hunger-striking prisoner be allowed to die?

PMID- 16086463
TI  - A question of property rights in the human body.

PMID- 16086464
TI  - Redefining the moment of death: implications on sustaining life.

PMID- 16086465
TI  - Involuntary civil commitment of the mentally ill: a system in need of change.

PMID- 16086466
TI  - The biotechnology revolution and its regulatory evolution.

PMID- 16086467
TI  - Language of publication restrictions in systematic reviews gave different results
      depending on whether the intervention was conventional or complementary.
AB  - OBJECTIVE: To assess whether language of publication restrictions impact the
      estimates of an intervention's effectiveness, whether such impact is similar for
      conventional medicine and complementary medicine interventions, and whether the
      results are influenced by publication bias and statistical heterogeneity. STUDY
      DESIGN AND SETTING: We set out to examine the extent to which including reports
      of randomized controlled trials (RCTs) in languages other than English (LOE)
      influences the results of systematic reviews, using a broad dataset of 42
      language-inclusive systematic reviews, involving 662 RCTs, including both
      conventional medicine (CM) and complementary and alternative medicine (CAM)
      interventions. RESULTS: For CM interventions, language-restricted systematic
      reviews, compared with language-inclusive ones, did not introduce biased results,
      in terms of estimates of intervention effectiveness (random effects ration of
      odds rations ROR=1.02; 95% CI=0.83-1.26). For CAM interventions, however,
      language-restricted systematic reviews resulted in a 63% smaller protective
      effect estimate than language-inclusive reviews (random effects ROR=1.63; 95%
      CI=1.03-2.60). CONCLUSION: Language restrictions do not change the results of CM
      systematic reviews but do substantially alter the results of CAM systematic
      reviews. These findings are robust even after sensitivity analyses, and do not
      appear to be influenced by statistical heterogeneity and publication bias.

PMID- 16086468
TI  - A surrogate mother contract to bear a child.

PMID- 16086469
TI  - Legal and policy implications of recent advances in prenatal diagnosis and fetal
      therapy.

PMID- 16086470
TI  - The competent child's preference in clinical medical decisions: a proposal for
      its consideration.

PMID- 16086471
TI  - Parents, judges, and a minor's abortion decisions: third party participation and
      the evolution of a judicial alternative.

PMID- 16086472
TI  - The razor's edge of human bonding: artificial fathers and surrogate mothers.

PMID- 16086473
TI  - Family law I: abortion.

PMID- 16086474
TI  - The right to privacy: Roe v. Wade revisited.

PMID- 16086475
TI  - In a quasi-simultaneous assessment, imprecise cholesterol monitoring and
      screening tests were improved.
AB  - OBJECTIVE: To calibrate Reflotron-measured capillary total cholesterol (cTC)
      relative to a laboratory-measured venous total cholesterol (vTC) criterion
      standard for monitoring and screening hypercholesterolemia. STUDY DESIGN AND
      SETTING: Quasi-simultaneous assessment in 1999-2002 of Reflotron cTC and
      laboratory vTC in a random sample of 4,269 adult residents of Geneva, Switzerland
      (calibration development subsample n=3,067; validation subsample n=1,172), by
      means of bias, precision, correlation, sensitivity, and false positive percentage
      (calculated as 100-specificity) analyses of Reflotron cTC vs. laboratory vTC
      measures for predicting hypercholesterolemia. RESULTS: Total bias was small (
      0.26 mmol/L), but there was substantial negative drift in Reflotron cTC (annual
      biases +0.08, -0.17, -0.27, and -0.60 mmol/L in 1999-2002). Overall, 57% of
      Reflotron cTC measurements for 894 hypercholesterolemic patients underestimated
      laboratory vTC (2%, 57%, 71%, and 98% in 1999-2002). Prior to calibration,
      sensitivity was 73% for the development and 35% for the validation subsample,
      with false positive at 4% (development) and 0.1% (validation). After calibration,
      sensitivity was 78% for the development and 37% for the validation subsample,
      with false positive at 5% (development) and 0.2% (validation). Using 95% upper
      prediction limits (UPL) for individual vTC values increased sensitivity to 99%
      and 83% and false positive percentage to 30% and 7% for the development and
      validation subsamples, respectively. CONCLUSION: Crude results of Reflotron
      measured cTC have poor sensitivity. Instead, 95% UPL can be used for monitoring
      and screening. Simply adding 0.8 mmol/L to a patient's observed Reflotron cTC
      value provides a very good approximation to the 95% UPL.

PMID- 16086476
TI  - Genesis retold: legal issues raised by the cryopreservation of preimplantation
      human embryos.

PMID- 16086477
TI  - Assisted suicide and the competent terminally ill: on ordinary treatments and
      extraordinary policies.

PMID- 16086478
TI  - The conflict between reason and will in the legislation of surrogate motherhood.

PMID- 16086479
TI  - Sterilisation of the intellectually disabled: the need for legislative reform.
AB  - This article examines the recent decision of the Full Court of the Family Court
      in Re Marion dealing with the question of sterilisation of intellectually
      disabled minors and in particular, the question of whether a parent or guardian
      can lawfully consent to a sterilisation operation upon an intellectually disabled
      minor or whether court approval is required before such an operation can lawfully
      be performed. The article goes on to critically examine legislation in force in
      various Australian jurisdictions concerning involuntary sterilisations and
      substituted consent as well as legislative reforms that have been proposed in
      this area.

PMID- 16086481
TI  - Gender bias in health care: a life or death issue for women with coronary heart
      disease.

PMID- 16086480
TI  - The application of traditional criminal law to misappropriation of gametic
      materials.

PMID- 16086482
TI  - The Casey undue burden standard: problems predicted and encountered, and the
      split over the Salerno test.

PMID- 16086483
TI  - Surveys of Norwegian youth indicated that breast feeding reduced subsequent risk
      of obesity.
AB  - BACKGROUND AND OBJECTIVE: Breast-feeding protects against overweight in
      childhood, while it is uncertain if it is protective against adolescent and adult
      overweight. The objective of this study was to examine whether having been breast
      fed protects against adolescent and adult overweight and obesity. METHODS:
      Participants in the Oslo Youth study examined in 1979/1981 (n=635, mean age 13.1
      years) and in 1999. Weight and height were measured in 1979/1981 and self
      reported in 1999. Breast-feeding information was provided by the parents in
      1979/1981. Potential confounders adjusted for included parents' body mass index
      and education, mother's smoking habits, participants' physical activity, smoking
      status, education and energy intake. RESULTS: Comparing those having been breast
      fed more than 3 months with those never breast fed, the adjusted odds ratios (95%
      confidence interval [CI]) between the two groups were 0.27 (0.13-0.56) for being
      overweight and 0.15 (0.03-0.72) for being obese in adolescent. In adulthood, the
      corresponding odds ratios were 0.64 (0.33-1.26) and 0.34 (0.12-1.01),
      respectively. CONCLUSION: Breast feeding during infancy appears to protect
      against adolescent overweight and obesity, while the effect on adult weight
      status is weaker. With increasing age, the impact of any protective physiologic
      mechanisms of breast feeding seen earlier in life tends to diminish.

PMID- 16086484
TI  - Constructing competence: formulating standards of legal competence to make
      medical decisions.

PMID- 16086485
TI  - Physician-assisted suicide: a "right" reserved for only the competent?

PMID- 16086486
TI  - Life after death: preservation of the immortal seed.
AB  - In today's brave new world, women who suffer the loss of their husband or lover
      can call upon medical science to create a souvenir baby. The rights of the
      decedent over his genetic material and the rights of the child who is created
      therefrom are the subject of an evolving legal process. This Essay examines
      legal, moral and ethical issues which arise from post-mortem artificial
      insemination. It discusses the attendant conflicts of procreative rights,
      finality of probate, psychological issues, international law, and recent cases.
      Ultimately, comprehensive legislation must be enacted to address these issues.

PMID- 16086487
TI  - The need to know versus the right to know: privacy of patient medical data in an
      information-based society.
AB  - "Whatever, in connection with my professional practice, or not in connection with
      it, I see or hear, in the life of men, which ought not to be spoken of abroad, I
      will not divulge, as reckoning that all such should be kept secret."(1)
      "Safeguards to privacy in individual health care information are imperative to
      preserve the health care delivery relationship and the integrity of the patient
      record."(2) As early as the fourth and fifth centuries B.C., Hippocrates
      contemplated the importance of medical information to the care and treatment of
      patients. His oath suggests that privacy of a patient's medical information
      creates the foundation upon which a patient reposes trust in his or her
      physician. While defining the earliest version of the physician-patient
      privilege, the oath does not envision the extent of modern day access to
      healthcare information. A patient's relationship with the modern healthcare
      delivery system often includes a team of physicians, nurses, and other clinical
      support personnel. This relationship extends beyond direct caregivers and may
      include healthcare administrators, payor organizations, and persons unfamiliar
      with a patient's identity, such as researchers and public health officials.
      Accessing a patient's medical information links these participants to the
      patient's healthcare delivery relationship. The Hippocratic Oath does not
      contemplate such broad access, nor does it contemplate the emerging privacy
      crisis resulting from the application of computer technology to medical record
      storage and retrieval. The combination of broad access, individual privacy
      rights, and computer technology requires a rethinking of measures designed to
      protect the realities of the modern medical information society.

PMID- 16086488
TI  - HIV-positive medical practitioners: legal and ethical obligations to disclose.

PMID- 16086489
TI  - Physician gag clauses--the hypocrisy of the Hippocratic Oath.

PMID- 16086490
TI  - AIDS-related risks in the health care setting: HIV testing of health care workers
      and patients.
AB  - Do patients and health care workers have the legal right to know each other's HIV
      status? Professor Flanagan argues that they do not. Given that with appropriate
      precautions the risk of transmitting HIV in the health care setting is extremely
      small and that the discriminatory consequences of HIV disclosure can be extremely
      high, it is suggested that the right of a patient or a health care worker not to
      disclose their HIV status must outweigh the other's "right to know."

PMID- 16086491
TI  - Two hit hypothesis for temporal lobe epilepsy.

PMID- 16086492
TI  - Parkinson's vaccine on trial.

PMID- 16086493
TI  - New mechanism for inclusion formation in neurodegeneration.

PMID- 16086494
TI  - Anchorless prion protein forms plaques.

PMID- 16086495
TI  - Remote memory: a neuroanatomical puzzle?

PMID- 16086496
TI  - Can gene therapy take the pain away?

PMID- 16086497
TI  - Channelopathy linked to epilepsy and paroxysmal dyskinesia.

PMID- 16086498
TI  - Protein instability and altered folding associated with ALS.

PMID- 16086499
TI  - But, why do we shoot horses?: an analysis of the right to die and euthanasia.

PMID- 16086500
TI  - The state's unqualified interest in preserving life: a critique of the
      formulations of life's sanctity in Washington v. Glucksberg.

PMID- 16086501
TI  - The importance of total number of sentinel lymph nodes in patients with stage N0
      cutaneous melanoma.
AB  - Staging of malignant melanoma now relies routinely on the sentinel node (SN)
      technique. On average, 2.1 SNs are removed per patient. Nevertheless, despite the
      success of the SN technique, approximately 10% of patients with negative SNs
      experience metastatic recurrence. Because a prior theoretical analysis using
      Poisson and Bayes probability models suggested that limited sampling of SNs could
      cause false-negative results, we undertook this study to see whether the subset
      of patients with negative SN and only 1 or 2 nodes examined have a shorter time
      to recurrence than patients with 3 or more nodes examined and found to be
      negative. Our study cases comprised 178 melanoma cases with SN biopsy: positive
      SN, 47; negative SN and fewer than 3 nodes examined, 68; and negative SN and more
      than 2 nodes examined, 63. Patients with negative SNs and fewer than 3 examined
      had disease-free survival intermediate between patients with positive SNs and
      those with negative SNs and more than 2 examined (P = .013). These results
      suggest that among patients with negative SNs, those with fewer than 3 nodes
      examined have greater risk for recurrence.

PMID- 16086502
TI  - A case study of new textualism in state courts: Doe v. Marselle and the
      confidentiality of HIV-related information.

PMID- 16086503
TI  - Surrogacy: the case for  full contractual enforcement.

PMID- 16086504
TI  - Inappropriate statistics in coagulation collection tube comparison study.

PMID- 16086505
TI  - Coercion and mental health treatment.

PMID- 16086506
TI  - An intimate passing: restoring the role of family and religion in dying.

PMID- 16086507
TI  - This is who will die when doctors are allowed to kill their patients.

PMID- 16086508
TI  - Can the right to autonomy be resuscitated after Glucksberg?

PMID- 16086509
TI  - Contraception or incarceration: what's wrong with this picture?

PMID- 16086510
TI  - Assisted suicide: the state versus the people.

PMID- 16086511
TI  - Healthcare surrogacy laws: implications for gay and lesbian families.

PMID- 16086512
TI  - Controlling the reproductive rights of impoverished women: is this the way to
      "reform" welfare?

PMID- 16086513
TI  - Fetal tissue research: state regulation of the donation of aborted fetuses
      without the consent of the "mother".

PMID- 16086514
TI  - Right to die--court requires clear and convincing evidence of persistent
      vegetative patient's intent to terminate life-sustaining procedures; Health Care
      Decisions Act of 1993 casts new light on outcome.

PMID- 16086515
TI  - Forced abortions and involuntary sterilization in China: are the victims of
      coercive population control measures eligible for asylum in the United States?
AB  - This Article discusses the propriety of granting political asylum to Chinese
      citizens fleeing China's coercive population control policy. It argues that China
      is persecuting some of its citizens through its population control policy and
      that the United States should grant asylum to those who have been persecuted or
      who have a genuine fear of future persecution.

PMID- 16086516
TI  - Whose life is it anyway?: an analysis and commentary on the emerging law of
      physician-assisted suicide.

PMID- 16086517
TI  - State AIDS-related legislation in the 1990s: adopting a language of hope which
      affirms life.

PMID- 16086518
TI  - Recognizing a fundamental liberty interest protecting the right to die: an
      analysis of statutes which criminalize or legalize physician-assisted suicide.
AB  - Physician-assisted suicide is one of the most controversial issues in society
      today. We live in an age where medical technology has developed so fast and so
      far that those who would have swiftly succumbed to deadly diseases in the not too
      distant past are now living, or, rather, being kept alive long past the point of
      meaningful existence. Although everyone sympathizes with the painful plight of
      the terminally ill, the specter of physician-assisted suicide gives many pause,
      and rightfully so: one need only think of the carbon monoxide contraption in the
      back of Dr. Death's infamous van to realize that society must address the issue
      of the right to die. Is there any solution to this great debate? In this note,
      Mr. William Tarnow passionately answers in the affirmative. Mr. Tarnow analyzes
      the constitutionality of state statutes which either criminalize or legalize
      physician-assisted suicide under both the Due Process and Equal Protection
      Clauses of the Constitution of the United States. The note also considers the
      case law, largely from the federal Ninth Circuit Court of Appeals, invalidating
      and upholding such statutes under the Constitution. Arguing that there is indeed
      a constitutional liberty interest in physician-assisted suicide, Mr. Tarnow
      concludes by suggesting that state legislatures can and must create legislation
      that legalizes physician-assisted suicide and passes constitutional muster.

PMID- 16086520
TI  - A plea for the enforceability of gestational surrogacy contracts.

PMID- 16086519
TI  - The worst of both worlds?: parental involvement requirements and the privacy
      rights of mature minors.

PMID- 16086521
TI  - Adding constitutional depravation to untimely death: South Dakota's living will
      pregnancy provision.
AB  - In 1991, the South Dakota Legislature enacted a living will statute. Included is
      a pregnancy provision that prevents pregnant women from obtaining the full
      benefit of the statute. A South Dakota Attorney General's opinion was released
      discussing the conflict of laws problems posed by the statute. That opinion,
      however, did not address the more important question of the constitutionality of
      the pregnancy provision. This comment analyzes the pregnancy provision under the
      Due Process, Equal Protection, and the Establishment Clauses and concludes that
      South Dakota's pregnancy provision is unconstitutional under all three doctrines.

PMID- 16086522
TI  - Justiciability--waiving for the flag: should informed consent rules apply in the
      context of military emergencies?

PMID- 16086523
TI  - Euthanasia and death with dignity: still poised on the fulcrum of homicide.
AB  - This article questions whether the law of homicide is an appropriate mechanism to
      adjudicate the humanitarian issues involved in voluntary euthanasia; particularly
      where painful protracted dying appears inherently more harmful than euthanasia.
      The author suggests that even if euthanasia can provide death with dignity this
      will not be achieved while the law requires the undignified criminalisation of
      the practitioner.

PMID- 16086524
TI  - The right to assisted suicide in Washington and Oregon: the courts won't allow a
      northwest passage.

PMID- 16086525
TI  - Constitutional considerations underlie Missouri's expansion of fetal rights
      within its wrongful death statute.

PMID- 16086526
TI  - Renewed compassion for the dying in Compassion in Dying v. State of Washington.

PMID- 16086527
TI  - Tragic choices: state discretion over organ transplant funding for Medicaid
      recipients.

PMID- 16086528
TI  - The Supreme Court's decision to recognize a psychotherapist privilege in Jaffee
      v. Redmond, 116 S. Ct. 1923 (1996): the meaning of "experience and the role of
      "reason" under Federal Rule of Evidence 501.

PMID- 16086529
TI  - When the surgeon has HIV: what to tell patients about the risk of exposure and
      the risk of transmission.

PMID- 16086530
TI  - Prescription rates and diagnostic patterns are stable: a comparison of high-,
      medium- and low-prescribing primary care physicians treating community-acquired
      respiratory tract infections.
AB  - The objective was to study prescription practices of primary care physicians in
      prescribing antibiotics for community-acquired respiratory tract infections.
      Design was time series analysis and cross-sectional survey. The setting was 30
      community primary health care centres. A case report form was completed for 3478
      patient consultations treated by 198 office-based primary care physicians. Main
      outcome measures were: classification of diagnoses of respiratory tract
      infections made by each physician; number of antibiotic prescriptions related to
      these diagnoses; each physician's mean weekly number of antibiotic prescriptions
      during 6 months before and after the survey. Patients' risk (odds ratio: OR) to
      receive an antibiotic prescription from the high and medium prescribers was 5.81
      (95% confidence interval [CI] 4.85-6.96) and 2.41 (95% CI 2.04-2.86), compared to
      low prescribers. High and medium prescribers made more diagnoses of otitis media
      (OR 2.07, 95% CI 1.70-2.53 and 1.85, 95% CI 1.51-2.26, respectively) and fewer
      diagnoses of unspecified upper respiratory tract infection (OR 0.32, 95% CI 0.26
      0.38 and 0.57, 95% CI 0.48-0.68, respectively) than low prescribers. The rank of
      the prescription rate of high, medium and low prescriber groups remained the same
      for all diagnoses except pneumonia. In addition, the annual rank between high,
      medium and low prescriber groups remained stable; high group prescribed more
      antibiotics during the year than medium group, which prescribed more than low
      prescriber group.

PMID- 16086531
TI  - Specialty hospitals: can general hospitals compete?
AB  - The rapid increase in specialty cardiac, surgical, and orthopedic hospitals has
      captured the attention of general hospitals and policymakers. Although the number
      of specialty hospitals remains small in absolute terms, their entry into certain
      health care markets has fueled arguments about the rules of "fair" competition
      among health care providers. To allow the smoke to clear, Congress effectively
      stalled the growth in new specialty hospitals by temporarily prohibiting
      physicians from referring Medicare or Medicaid patients to specialty hospitals in
      which they had an ownership interest. During this 18-month moratorium, which
      expired June 8, 2005, two mandated studies of specialty hospitals provided
      information to help assess their potential effect on health care delivery. This
      issue brief discusses the research on specialty hospitals, including their
      payments under Medicare's hospital inpatient payment system, the quality and cost
      of care they deliver, their effect on general hospitals and on overall health
      care delivery, and the regulatory and legal environment in which they have
      proliferated. It concludes with open issues concerning physician self-referral
      and the role of general hospitals in providing a range of health care services.

PMID- 16086532
TI  - Effect of meditation on ultraweak photon emission from hands and forehead.
AB  - BACKGROUND: Various physiologic and biochemical shifts can follow meditation.
      Meditation has been implicated in impacting free radical activity. Ultraweak
      photon emission (UPE, biophoton emission) is a constituent of the metabolic
      processes in a living system. Spectral analysis showed the characteristics of
      radical reactions. OBJECTIVES: Recording and analysing photon emission in 5
      subjects before, during and after meditation. METHODS: UPE in 5 subjects who
      meditated in sitting or supine positions was recorded in a darkroom utilising a
      photomultiplier designed for manipulation in three directions. RESULTS: Data
      indicated that UPE changes after meditation. In 1 subject with high pre
      meditation values, UPE decreased during meditation and remained low in the
      postmeditation phase. In the other subjects, only a slight decrease in photon
      emission was found, but commonly a decrease was observed in the kurtosis and
      skewness values of the photon count distribution. A second set of data on photon
      emission from the hands before and after meditation was collected from 2
      subjects. These data were characterised by the Fano factor, F(T), i.e. variance
      over mean of the number of photoelectrons observed within observation time T. All
      data were compared to surrogate data sets which were constructed by random
      shuffling of the data sets. In the pre-meditation period, F(T) increased with
      observation time, significantly at time windows >6 s. No such effect was found
      after meditation, when F(T) was in the range of the surrogate data set.
      CONCLUSIONS: The data support the hypothesis that human photon emission can be
      influenced by meditation. Data from time series recordings suggest that this non
      invasive tool for monitoring radical reactions during meditation is useful to
      characterise the effect of meditation. Fano factor analysis demonstrated that the
      time series before meditation do not represent a simple Poisson process. Instead,
      UPE has characteristics of a fractal process, showing long-range correlations.
      The effect of meditation waives out this coherence phenomenon, suggesting a
      weaker and less ordered structure of UPE. In general, meditation seems to
      influence the complex interactions of oxidative and anti-oxidative reactions
      which regulate photon emission. The reason for the statistical changes between
      pre- and post-meditation measurements remains unclear and demands further
      examination.

PMID- 16086533
TI  - High society: drugs, mental health, and the history of psychiatry.

PMID- 16086534
TI  - Listening to the past: history, psychiatry, and anxiety.
AB  - This article explores the history of psychiatry and the rise of biological
      psychiatry and suggests ways in which the study of history can shed light on
      current psychiatric practice and debate. Focusing on anxiolytics (meprobomate in
      the 1950s and benzodiazepines in the 1960s, 1970s, and 1980s) as a case study in
      the development of psychopharmacology, it shows how social and political factors
      converged to popularize and later stigmatize outpatient treatments for anxiety.
      The importance of social context in the creation of new therapeutic paradigms in
      modern psychiatry suggests the need to take into account a broad range of
      historical variables to understand how modern psychopharmacology has emerged and
      how particular treatments for disorders have been developed, diffused, and
      assessed.

PMID- 16086535
TI  - Flashback: psychiatric experimentation with LSD in historical perspective.
AB  - In the popular mind, d-lysergic acid diethylamide (LSD) research in psychiatry
      has long been associated with the CIA-funded experiments conducted by Ewen
      Cameron at the Allen Memorial Institute in Montreal, Quebec. Despite this
      reputation, a host of medical researchers in the post World War II era explored
      LSD for its potential therapeutic value. Some of the most widespread trials in
      the Western world occurred in Saskatchewan, under the direction of psychiatrists
      Humphry Osmond (in Weyburn) and Abram Hoffer (in Saskatoon). These medical
      researchers were first drawn to LSD because of its ability to produce a "model
      psychosis." Their experiments with the drug that Osmond was to famously describe
      as a "psychedelic" led them to hypothesize and promote the biochemical nature of
      schizophrenia. This brief paper examines the early trials in Saskatchewan,
      drawing on hospital records, interviews with former research subjects, and the
      private papers of Hoffer and Osmond. It demonstrates that, far from being fringe
      medical research, these LSD trials represented a fruitful, and indeed
      encouraging, branch of psychiatric research occurring alongside more famous and
      successful trials of the first generation of psychopharmacological agents, such
      as chlropromazine and imipramine. Ultimately, these LSD experiments failed for 2
      reasons, one scientific and the other cultural. First, in the 1950s and early
      1960s, the scientific parameters of clinical trials shifted to necessitate
      randomized controlled trials, which the Saskatchewan researchers had failed to
      construct. Second, as LSD became increasingly associated with student riots,
      antiwar demonstrations, and the counterculture, governments intervened to
      criminalize the drug, restricting and then terminating formal medical research
      into its potential therapeutic effects.

PMID- 16086536
TI  - Cost-utility of 2 maintenance treatments for older adults with depression who
      responded to a course of electroconvulsive therapy: results from a decision
      analytic model.
AB  - OBJECTIVE: The prevalence of major depressive disorder (MDD) in community
      dwelling elderly populations is 1% to 3%. After initial treatment of the acute
      phase of depression, only about 25% to 30% of elderly patients remain well after
      1 to 3 years of follow-up. Previous studies suggested that patients who received
      maintenance electroconvulsive therapy (MECT) demonstrated lower relapse rates, a
      better subjective sense of well-being, and lower health care costs at 12-month
      follow-up. This study provides a cost-utility analysis of 2 maintenance
      treatments for recurrent depression in elderly patients. METHOD: We used a Markov
      decision model to compare maintenance pharmacotherapy (MPT) with MECT in a
      theoretical cohort of elderly individuals with MDD who responded to an initial
      course of ECT. We estimated total costs and total quality-adjusted life years
      (QALYs) for each strategy as well as the cost per QALY. RESULTS: The model
      produced a cost per patient of dollar 436,102 for MPT and dollar 281,356 for
      MECT. The MPT strategy yielded 7.55 QALYs and the MECT strategy yielded 11.43
      QALYs. Therefore, MPT cost dollar 57,762 per QALY and MECT cost dollar 24,616 per
      QALY. CONCLUSION: Our model suggests that MECT may be more cost-effective than
      MPT in the maintenance treatment of older adults with depression who have
      responded to a course of acute ETC.

PMID- 16086537
TI  - Population-based use of mental health services and patterns of delivery among
      family physicians, 1992 to 2001.
AB  - OBJECTIVE: To examine 9-year rates of family physician (FP) and psychiatrist use,
      as well as patterns of mental health services delivery by FPs. METHOD: We used
      population-based data from Winnipeg, Manitoba, to construct mutually exclusive
      cohorts of adults treated for major or minor mental health disorders in fiscal
      years 1992-1993 to 2000-2001. For each year, we measured patterns of use in this
      population and patterns of mental health practice among FPs. RESULTS: The
      treatment prevalence rate was 224 per 1000 in 2000-2001 and 174 per 1000 in 1992
      1993, and the rates for major and minor mental health disorders increased over
      the 9-year period by 15% and 31%, respectively. In 2000-2001, 92% of adults
      treated for mental illness saw at least one FP, and 45% saw an FP but no
      psychiatrist. Adults with major or minor mental health disorders visited an FP on
      average 9.1 and 6.9 times yearly, respectively, and FP visit rates remained
      relatively stable. There was a gradient in use by socioeconomic status: adults
      from communities with lower socioeconomic status had the highest rates of use. By
      2000-2001, 24% of FPs billed for services related to psychosocial conditions as
      often as they did for the most frequent conditions seen in primary care.
      CONCLUSION: Between 1992-1993 and 2000-2001, the study population's patterns of
      FP and psychiatrist use remained relatively stable. In more recent years, FPs
      provided more mental health services than in previous years; this related to
      increased treatment prevalence rather than to increases in use per adult. FPs
      played a major role in the provision of mental health care.

PMID- 16086538
TI  - SCL-90-R and 16PF profiles of senior high school students with excessive internet
      use.
AB  - OBJECTIVE: To investigate the psychiatric symptomatology and personality
      characteristics of Korean senior high school students considered to use the
      Internet to excess. METHOD: We administered a questionnaire packet to students
      that included 4 measures. These measures included a questionnaire on Internet use
      patterns during the previous month, the Internet Addiction Test (IAT), the
      Symptom Checklist-90-R (SCL-90-R), and the Sixteen Personality Factor
      Questionnaire (16PF). A total of 328 students, aged 15 to 19 years, participated
      in the study. RESULTS: Students were divided into 4 Internet user groups
      according to their IAT total scores: nonusers (n = 59, 18.0%), minimal users (n =
      155, 47.3%), moderate users (n = 98, 29.9%), and excessive users (n = 16, 4.9%).
      The SCL-90-R showed that the excessive users group, when compared with the other
      groups in this study, reported the highest levels of symptomatology. The 16PF
      also revealed that excessive users were easily affected by feeling, emotionally
      less stable, imaginative, absorbed in thought, self-sufficient, experimenting,
      and preferred their own decisions. CONCLUSIONS: This study suggests that senior
      high school students who use the Internet to excess report and subsequently
      exhibit significantly more psychiatric symptoms than students who use the
      Internet less frequently. In addition, excessive users appear to have a
      distinctive personality profile when compared with nonusers, minimal, and
      moderate users.

PMID- 16086539
TI  - Open-label adjunctive topiramate in the treatment of unstable bipolar disorder.
AB  - OBJECTIVE: To assess open-label adjunctive topiramate in the treatment of
      outpatients with unstable bipolar disorder (BD). METHOD: Outpatients with DSM-IV
      defined BD (I or II) exhibiting mood instability were enrolled in this 16-week,
      open-label, multicentre study. Topiramate was added to existing mood stabilizers
      and other psychotropic treatments. The primary effectiveness measure was the
      Clinical Global Impression of Severity (CGI-S) scale; other scales included the
      Young Mania Rating Scale (YMRS) and the Montgomery-Asberg Depression Rating Scale
      (MADRS). Safety assessments included monitoring adverse events, measuring tremor,
      monitoring vital signs and weight, and laboratory indices. We also evaluated
      patient satisfaction with treatment. RESULTS: A total of 109 patients were
      enrolled. Intent-to-treat analysis showed significant improvement from baseline
      in the CGI-S, YMRS, and MADRS, starting at Week 2 (P < 0.001), with further
      accrual of benefit between Week 2 and Week 16 (P < 0.001). The mean modal dosage
      of topiramate during the stable dosing period was 180 mg daily. There was a mean
      1.8 kg decrease in patient weight from topiramate initiation to Week 16 (P <
      0.001). Topiramate was well tolerated by most patients; 11% withdrew from the
      study owing to adverse events. We noted a significant reduction in the mean
      severity score for preexisting tremor by Week 8 of treatment (P < 0.005); no
      notable changes in vital signs were observed. At Week 16, 50% of the patients
      were "completely satisfied" with topiramate treatment. CONCLUSIONS: Adjunctive
      topiramate treatment can reduce the severity of manic and depressive symptoms, as
      well as reducing tremor and weight in outpatients with BD I or II.

PMID- 16086540
TI  - [Obsessive-compulsive symptoms treatment in: schizophrenia].
AB  - Obsessive-compulsive symptoms (OCSs) frequently occur in schizophrenia and seem
      to worsen prognosis. Many case studies suggest that OCSs appear or worsen with an
      atypical antipsychotic agent treatment (that is, with risperidone, olanzapine,
      and clozapine). Therefore, family or personal history of OCS should be
      investigated before initiating such treatment, and OCS onset should be monitored
      during treatment. Clozapine is involved in most such cases. When OCSs appear with
      clozapine, dosage can be reduced and a serotonin reuptake inhibitor treatment
      added. Current studies suggest that patients with schizophrenia and OCSs should
      benefit from treatment with an antipsychotic and an antiobsessive medication. Two
      controlled trials deal with OCS treatment in schizophrenia: the first, with
      clomipramine; and the second, with fluvoxamine. Both have proven their efficacy,
      but these trials include a small number of patients with heterogeneous
      characteristics.

PMID- 16086541
TI  - Spontaneous parkinsonism in antipsychotic-naive patients with first-episode
      psychosis.
AB  - OBJECTIVE: The purpose of this study was to establish rates of spontaneous
      parkinsonism (SP) among the different types of psychosis. We hypothesized that
      the rate would be higher among persons with affective symptoms. METHODS: We
      included in the study consecutive patients admitted to a first-episode psychosis
      intervention program. We recorded sociodemographic data from interviews with
      patients and caregivers and from medical records. We used the Simpson-Angus
      Rating Scale at baseline to assess parkinsonism and a diagnosis of SP was
      established if the Simpson-Angus score was > or = 0.3. RESULTS: A total of 174
      patients were examined; of these, only 4 (2.3%; 2 Chinese women, 1 Chinese man,
      and 1 Malay man) had SP. There was a significant difference in the rates of SP in
      patients with affective psychosis and schizoaffective disorder, compared with
      those with nonaffective psychoses (15.4% vs 1.2%; chi2 = 10.7, P = 0.001). The 2
      groups did not differ significantly in age, duration of untreated psychosis, or
      sex distribution. CONCLUSIONS: The rate of SP in Asian patients with first
      episode psychosis was low, and it was significantly higher in those with
      affective symptoms.

PMID- 16086542
TI  - PET/CT in oncology: a major technology for cancer care.
AB  - PET-CT can image tumor metabolism, proliferation, hypoxia, and apoptosis with
      precise anatomic image fusion and will become an essential tool in the management
      of patients with cancer by its ability to assess the extent and severity of
      disease and treatment response. F-18 fluoro-2-deoxy-D-glucose (FDG) is the most
      frequently used radiopharmaceautical today and new F-18 labeled ligands are under
      development. It has changed dramatically the management of numerous cancers such
      brain tumors, head and neck cancers, thyroid cancer, parathyroid cancer, lung
      cancer, esophageal cancer, lymphoma, pancreatic cancer, colorectal cancer, and
      many others. Its utility for non-cancerous conditions is also gradually
      established. In this article the basic technology, the ligands available for
      routine clinical applications, and expected developments in the near future will
      be addressed. PET-CT will be used with increasing frequency and will become
      progressively used as a surrogate marker for disease response. Novel ligands,
      labeled with F-18, will further increase the clinical utility of this technology.

PMID- 16086543
TI  - FDG-PET in head and neck, and thyroid cancer.
AB  - FDG-PET has become a standard clinical imaging modality in patients with head and
      neck cancer. It contributes valuable information in localizing a primary tumor in
      patients with neck nodal metastases from an unknown primary, in the staging of
      primary head and neck cancer, and in the detection of recurrent disease. In
      addition, FDG-PET provides independent prognostic information in patients with
      newly diagnosed and recurrent head and neck cancer. PET-CT improves lesion
      localization and accuracy of FDG-PET and is strongly recommended in patients with
      head and neck cancer. After thyroidectomy, FDG-PET has proven useful in patients
      with clinical or serological evidence of recurrent or metastatic thyroid
      carcinoma but negative whole body iodine scan. PET shows metastatic disease in up
      to 90% of these patients, thereby providing a rational basis for further studies
      and therapy. In patients with medullary thyroid cancer with elevated calcitonin
      levels following thyroidectomy, FDG-PET has a sensitivity of 70-75% for
      localizing metastatic disease. Occasionally incidental intense FDG uptake is
      observed in the thyroid gland on whole-body PET studies performed for other
      indications. Although diffuse FDG uptake usually indicates thyroiditis, focal
      uptake has been related to thyroid cancer in 25-50% of cases and should therefore
      be evaluated further if a proven malignancy would cause a change in patient
      management.

PMID- 16086544
TI  - PET in lung cancer.
AB  - Accurate tumor staging is essential for choosing the appropriate treatment
      strategy in patients with lung cancer. It has already been shown that FDG-PET is
      highly accurate in classifying lung nodules as benign or malignant. Integrated
      PET-CT enables the exact matching of focal abnormalities on PET to anatomic
      structures on CT. PET-CT is superior in diagnostic accuracy for T staging and
      differentiation between tumor and peritumoral atelectasis. PET has also proved to
      be a very effective staging modality for mediastinal nodal staging. It has been
      demonstrated to assist mediastinoscopy to reveal additional mediastinal disease
      in 6% of patients. PET detects unexpected extrathoracic metastases in 10-20% of
      patients and changes therapeutic management in about 20% of patients. A very high
      accuracy of FDG-PET in distinguishing recurrent disease from benign treatment
      effects has been shown. Patients should be evaluated after a minimum of 2 months
      after completion of therapy. FDG-PET can be clinically used for selecting biopsy
      sites. At our institution PET-CT has become the standard imaging modality for
      staging patients with lung cancer. Although not all tumors take up FDG, other
      radiotracers are being studied to expand the utility of PET-CT. PET-CT offers
      many opportunities for the patients, the clinicians, and the researchers. PET-CT
      has the potential to become the most efficient oncologic examination in the near
      future.

PMID- 16086545
TI  - PET/CT in non-small-cell lung cancer: value of respiratory-gated PET.
AB  - The use of PET in the staging of patients with NSCLC is cost-effective, mainly
      due to a reduction in the number of futile operations. The addition of SUVmax to
      pathologic tumor size identifies a subgroup of patients at highest risk for death
      as a result of recurrent disease after resection. Tumor staging is more accurate
      with PET-CT than with CT alone or with PET alone. The greatest source of error in
      accurate localization and quantification on PET or PET-CT in lung cancer is
      respiratory motion. At MSKCC respiratory-gated PET (RGPET) is used in treatment
      planning. The lesion in the gated image is smaller in diameter than in the
      ungated image. Respiratory-correlated dynamic PET (RCDPET) can be considered an
      alternative method to RGPET. RCDPET shows very accurate local co-registration
      that can be used to make an attenuation correction and obtain an SUV. Gating
      gives a much clearer picture resulting in more than a one-third increase in the
      quantification. The SUV of lung lesions must be re-evaluated based on these
      techniques. This development will have important implications in areas such as
      the liver for controlling respiratory motion, which is a major problem in terms
      of lesion detection. We have successfully taken the first step in an attempt to
      correct for respiratory motion artifacts in PET imaging of lung lesions. (Chang

PMID- 16086546
TI  - Role of PET in lymphoma.
AB  - In Hodgkin's lymphoma (HL), PET imaging should be performed in all patients,
      particularly in stage I or II disease where change in staging will alter
      management. For aggressive Non-Hodgkin's lymphoma (NHL), PET imaging is valuable
      to provide a baseline for response evaluation. For indolent NHL, it is concluded
      that PET imaging is not generally indicated. For HL, a negative FDG-PET scan is
      highly indicative of long-term, disease-free survival and is particularly useful
      in the presence of residual CT mass. For aggressive NHL, a positive FDG-PET scan
      is predictive of disease persistence or recurrence. There is a significant
      incidence of false-negative FDG-PET scans, which in most cases means minimal
      residual disease that cannot be detected by the current instrumentation. For both
      NHL and aggressive HL, early assessment of response appears to be predictive of
      long-term outcome. Optimal time of FDG-PET scan during therapy needs to be
      determined. For indolent NHL, the high rate of false-negative FDG-PET scans
      raises questions to its clinical role in response evaluation. FDG-PET and PET-CT
      improve primary staging and restaging of lymphomas. Metabolic imaging will be the
      standard technology for assessment of therapy with documented prognostic value.
      Imaging during therapy may be valuable to individualize therapeutic protocols and
      to define chemosensitivity of tumor tissue. Minimal residual disease cannot be
      detected with current imaging devices.

PMID- 16086547
TI  - Comparison of referral and non-referral hypertensive disorders during pregnancy:
      an analysis of 271 consecutive cases at a tertiary hospital.
AB  - BACKGROUND: This retrospective cohort study analyzed the clinical manifestations
      in patients with preeclampsia and eclampsia, assessed the risk factors compared
      to the severity of hypertensive disorders on maternal and perinatal morbidity,
      and mortality between the referral and non-referral patients. METHODS: 271
      pregnant women with preeclampsia and eclampsia were assessed (1993 to 1997). Chi
      square analysis was used for the comparison of categorical variables, and the
      comparison of the two independent variables of proportions in estimation of
      confidence intervals and calculated odds ratio of the referral and non-referral
      groups. Multivariate logistic regression was used for adjusting potential
      confounding risk factors. RESULTS: Of the 271 patients included in this study, 71
      (26.2%) patients were referrals from other hospitals. Most of the 62 (87.3%)
      referral patients were transferred during the period 21 and 37 weeks of
      gestation. Univariate analysis revealed that referral patients with hypertensive
      disorder were significantly associated with SBP > or =180, DBP > or =105, severe
      preclampsia, haemolysis, elevated liver enzymes, low platelets (HELLP), emergency
      C/S, maternal complications, and low birth weight babies, as well as poor Apgar
      score. Multivariate logistic regression analyses revealed that the risk factors
      identified to be significantly associated with increased risk of referral
      patients included: diastolic blood pressure above 105 mmHg (adjusted odds ratio,
      2.09; 95 percent confidence interval, 1.06 to 4.13; P = 0.034), severe
      preeclampsia (adjusted odds ratio, 3.46; 95 percent confidence interval, 1.76 to
      6.81; P < 0.001), eclampsia (adjusted odds ratio, 2.77; 95 percent confidence
      interval, 0.92 to 8.35; P = 0.071), HELLP syndrome (adjusted odds ratio, 18.81;
      95 percent confidence interval, 2.14 to 164.99; P = 0.008). CONCLUSION: The
      significant factors associated with the referral patients with hypertensive
      disorders were severe preeclampsia, HELLP, and eclampsia. Lack of prenatal care
      was the major avoidable factor found in referral and high risk patients. Time
      constraints relating to referral patients and the appropriateness of patient
      centered care for patient safety and better quality of health care need further
      investigation on national and multi-center clinical trials.

PMID- 16086549
TI  - Use of a galeopericranial flap for the reconstruction of anterior cranial base
      defects.
AB  - BACKGROUND: To evaluate the efficacy of using a galeopericranial flap for
      reconstruction of anterior cranial base defects. METHODS: In Linkou Chang Gung
      Memorial Hospital from February 1994 to November 2003, 25 patients who had tumors
      of the skull base underwent craniofacial resection, and a galeopericranial flap
      was used to reconstruct the anterior cranial base defect. The galeopericranial
      flap was developed and based on at least 1 side of the supraorbital or
      supratrochlear arteries and veins; it was only raised from the scalp after the
      tumor had been removed. It was then turned inwardly and intracranially and was
      transposed to lie between the skull base bone and the dura. No free skin or bone
      grafts were used. RESULTS: Two patients experienced flap failure, and salvage was
      subsequently performed using a free vastus lateralis flap for skull base repair.
      Thus, the flap failure rate was 8% (2/25). CONCLUSIONS: The delicate nature and
      great pliability of a galeopericranial flap make it unique and competent for
      reconstructions of anterior skull base defects. Its ready availability, valid
      strength, and sufficient axial blood supply provide a satisfactory barrier for
      isolating the cranial cavity from the underlying respiratory tract, with minimal
      morbidity and mortality.

PMID- 16086548
TI  - Prognostic significance of intratumoral natural killer cells in primary resected
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: Natural killer (NK) cells are important effector cells in the defense
      against tumors. The present study retrospectively examines the intratumoral NK
      cells in primary resected esophageal squamous cell carcinoma (ESCC) and the
      correlation between the patient' outcome and the intratumoral NK cells
      infiltration. METHODS: Immunohistochemistry was used to analyze the intratumoral
      NK cell infiltration in 38 archival specimens from patients with primary resected
      ESCC. RESULTS: According to the cut-off point of the staining for intratumoral NK
      cell infiltration, 14 (37%) cases had high level infiltration and 24 (63%) low.
      The 5-year survival of patients with high level NK infiltration was significantly
      better than that of patients with a low level of NK infiltration (p < 0.01).
      Multivariate analysis did not show NK cell infiltration to be a significant
      prognostic factor. CONCLUSIONS: Intratumoral NK cell infiltration is associated
      with a favorable outcome in ESCC. Intratumoral NK cell infiltration might be used
      as a variable with prognostic value in primary resected ESCC.

PMID- 16086550
TI  - Motor control in patients with incomplete spinal cord injuries and various
      voluntary movement capabilities.
AB  - BACKGROUND: In this study, we attempted to verify the hypothesis that further
      improvements in volitional movement of patients with a spinal cord injury would
      diminish and ultimately suppress the segmental responses, while enhancing the
      supraspinal inhibitory influence. METHODS: Eleven patients with an incomplete
      spinal cord injury and partial preservation of motor function (ASIS grades C and
      D) were recruited. Their lower limbs were evaluated using polyelectromyography
      (PEMG) during voluntary movements, reinforcement maneuvers, tonic vibratory
      reflex, passive stretch reflex, irradiation of the passive stretch reflex
      (PSRirrad), and plantar reflex suppression. RESULTS: The reinforcement maneuver
      response, tonic vibratory response, passive stretch reflex, and PSRirrad were
      most active in limbs with partially preserved volitional movement, but for which
      patients were still incapable of lifting their heel off the examination table. In
      contrast, plantar reflex suppression was strongest in limbs with partially
      preserved volitional movement, for which patients were capable of lifting the
      heel off the examination table. CONCLUSIONS: Supraspinal inhibitory effects were
      most active in those limbs which were capable of lifting the heel off the
      examination table, compared to limbs with partially preserved volitional activity
      but without visible movement or which were incapable of lifting the heel off the
      examination table. The capability for volitional activity paralleled the
      supraspinal inhibitory effects.

PMID- 16086551
TI  - Adenoid cystic carcinoma of the trachea: a report of seven cases and literature
      review.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) of the trachea is rare. The clinical
      manifestations, natural history, and responses to therapy differ from those of
      other malignant tracheal tumors. METHOD: In this retrospective study, we examined
      pathological records of patients in the Department of Pathology at Chang Gung
      Memorial Hospital from 1990 through 2002. There were five male patients and two
      female patients with ages that ranged from 21 to 55 years. For these seven
      patients the clinical manifestations and period from initial symptoms to
      diagnosis, treatment and outcome are presented. RESULTS: Hemoptysis,
      nonproductive cough, dyspnea, chest pain and weight loss were the frequent early
      manifestations. Five patients had tumors in the lower area of the trachea, two
      had tumors in the upper area of the trachea. In a patient with the tumor in the
      upper area of the trachea, the tumor involved the cricoid ring, larynx, and
      subglottic area. In one patient with the tumor in the lower area of the trachea,
      the tumor invaded the right lower lobe of the lung. The longest survival time was
      more than 10 years. CONCLUSIONS: ACC is a rare primary tracheal malignancy. The
      time from first symptoms to diagnosis varied, ranging from weeks to more than 1
      year. Complete surgical resection provides the patient with the best chance of
      prolonged survival or even complete remission.

PMID- 16086552
TI  - Phenylalanine 4-monooxygenase and the S-oxidation of S-carboxymethyl-L-cysteine
      in HepG2 cells.
AB  - The role of phenylalanine 4-monooxygenase (PAH) in the S-oxidation of S
      carboxymethyl-L-cysteine (SCMC) in the rat has now been well established in rat
      cytosolic fractions in vitro. However, the role of PAH in the S-oxidation of SCMC
      in human cytosolic fractions or hepatocytes has yet to be investigated. The aim
      of this investigation was to analyse the kinetic parameters of PAH oxidation of
      both L-phenylalanine (Phe) and SCMC in the human HepG2 cell line in order to
      investigate the use of these cells as a model for the cellular regulation of SCMC
      S-oxidation. The experimentally determined Km and V(max) were 7.14 +/- 0.32 mM
      and 0.85 +/- 0.32 nmole Tyr formed min(-1) x mg protein(-1) using Phe as
      substrate. For SCMC the values were 25.24 +/- 5.91 mM and 0.79 +/- 0.09 nmole
      SCMC (RIS) S-oxides formed min(-1) x mg protein(-1). The experimentally
      determined Km and V(max) for the cofactor BH4 were 6.81 +/- 0.21 microM and 0.41
      +/- 0.004 nmole Tyr formed min(-1) x mg protein(-1) for Phe and 7.24 +/- 0.19
      microM and 0.42 +/- 0.002 nmole SCMC (R/S) S-oxides formed min(-1) x mg protein(
      1) for SCMC. The use of various PAH inhibitors confirmed that HepG2 cells
      contained PAH and that the enzyme was capable of converting SCMC to its (R) and
      (S) S-oxide metabolites in an in vitro PAH assay. Thus HepG2 cells have become a
      useful additional tool for the investigation of the cellular regulation of PAH in
      the S-oxidation of SCMC.

PMID- 16086553
TI  - Preventing hepatocyte oxidative stress cytotoxicity with Mangifera indica L.
      extract (Vimang).
AB  - Vimang is an aqueous extract of Mangifera indica used in Cuba to improve the
      quality of life in patients suffering from inflammatory diseases. In the present
      study we evaluated the effects of Vimang at preventing reactive oxygen species
      (ROS) formation and lipid peroxidation in intact isolated rat hepatocytes. Vimang
      at 20, 50 and 100 microg/ml inhibited hepatocyte ROS formation induced by glucose
      glucose oxidase. Hepatocyte cytotoxicity and lipid peroxidation induced by cumene
      hydroperoxide was also inhibited by Vimang in a dose and time dependent manner at
      the same concentration. Vimang also inhibited superoxide radical formation by
      xanthine oxidase and hypoxanthine. The superoxide radical scavenging and
      antioxidant activity of the Vimang extract was likely related to its gallates,
      catechins and mangiferin content. To our knowledge, this is the first report of
      cytoprotective antioxidant effects of Vimang in cellular oxidative stress models.

PMID- 16086554
TI  - Beta1- or beta2-blockers to improve hemodynamics following endotracheal
      adrenaline administration.
AB  - BACKGROUND: The recommended dose for endotracheal adrenaline (0.02 mg/kg) causes
      a pronounced initial decrease in diastolic blood pressure which is detrimental at
      the initial phase of cardiopulmonary resuscitation. This effect was previously
      attributed to an early and preferential stimulation of the beta-adrenergic
      receptors causing vasodilatation unopposed by an alpha-adrenergic
      vasoconstriction. We hypothesized that inhibition of the beta2-adrenoreceptors is
      responsible for prevention of the deleterious initial decrease in blood pressure
      that takes place following endotracheal administration of adrenaline. METHODS:
      Adrenaline (0.02 mg/kg) diluted with normal saline (5 ml) was injected into the
      endobronchial tree of anesthetized dogs 3 min following pretreatment with the non
      selective beta-blocker propranolol, selective beta1-blocker metoprolol (0.1
      mg/kg, i.v.), or without pre-treatment. Heart rate, blood pressure and arterial
      blood gases were monitored. RESULTS: The selective beta-blocker metoprolol was
      almost as effective as the non-selective beta-blocker propranolol in attenuating
      the initial decrease in blood pressure following endotracheally administered
      adrenaline, a phenomenon that was previously attributed to inhibition of beta
      adrenoreceptors. CONCLUSIONS: The outcome of this study might be explained by a
      dose-related loss of cardioselectivity of metoprolol. Further studies are
      warranted to refine the pharmacological means to abort the initial blood pressure
      lowering effect of endotracheally administered adrenaline.

PMID- 16086555
TI  - Involvement of nitric oxide in clonidine-induced spinal analgesia.
AB  - BACKGROUND: The chronic pain relieving effects following spinal administration of
      clonidine are probably connected to alpha2-adrenoreceptor-induced augmented
      synthesis of nitric oxide (NO) in the spinal cord. In contrast, when acute pain
      is considered, the possible role of NO is still speculative. The aim of the
      present study was to explore the role of NO in acute pain relief following
      intraspinal administration of clonidine. METHODS: We used the mouse tail-flick
      model of acute pain. Spinal injections of the following agents and their
      combinations were administered: clonidine, L-arginine (NO precursor), the NO
      production inhibitor nitro-L-arginine-methyl ester (L-NAME), the NO antagonist
      methylene blue (MB) and nitroglycerine (NO releasing agent). RESULTS: A 95%
      analgesic response was achieved with 2.0 microg clonidine. L-Arginine produced
      analgesia, and L-arginine administration followed by clonidine resulted in a
      pronounced synergistic analgesic effect. This synergistic effect was attenuated
      by L-NAME. Pre-treatment with MB decreased and nitroglycerine administration did
      not affect the clonidine-induced analgesia. CONCLUSIONS: NO may be involved in
      the mediation of the acute pain relieving effects of intraspinally administered
      clonidine. Further research is warranted to establish the potential benefits and
      possibility for incorporation of NO promoting agents in therapeutic regional pain
      regimens.

PMID- 16086556
TI  - Cerebroventricular injection of clonidine causes analgesia mediated by a nitrogen
      pathway.
AB  - Whereas neuroaxially administered clonidine produces analgesia partially mediated
      by alpha2-adrenoceptor-induced augmented synthesis of nitric oxide (NO), the
      central mechanisms by which clonidine produces its antinociceptive effects are
      still speculative. We used the tail-flick model of acute pain in mice to further
      explore the role of NO in mediating clonidine-induced central analgesia.
      Cerebroventricular administration of the following agents was studied: clonidine,
      L-arginine (NO precursor), the NO production inhibitor nitro-L-arginine-methyl
      ester (L-NAME), the NO antagonist methylene blue (MB), and nitroglycerine (NO
      releasing agent). Analgesic response was achieved with clonidine and L-arginine.
      Simultaneous administration of L-arginine and clonidine produced no additive
      analgesic effect. Prior administration of L-NAME or MB partially abolished the
      clonidine-induced analgesic effect, whereas nitroglycerine administration did not
      affect it. NO may be involved in the mediation of the central antinociceptive
      effects of clonidine. Further investigation is necessary to determine the
      possible role of NO-promoting agents in analgesia when co-administered with
      clonidine.

PMID- 16086557
TI  - Susceptibility to some antifungal drugs of vaginal lactobacilli isolated from
      healthy women.
AB  - Samples were taken from the lateral vaginal wall of 19 healthy women.
      Lactobacilli were isolated from ten of these women. Fifty-eight Lactobacillus
      isolates were identified as L. gasseri, L. vaginalis, L. acidophilus, L.
      delbrueckii spp. lactis, L. crispatus, L. plantarum, L. cellobiosus, L. jensenii,
      L. salivarius, L. curvatus, L. brevis and L. oris. The inhibitory effect of
      isoconazole and oxiconazole in 0.2, 0.1 and 0.05 microg/ml concentrations on 58
      Lactobacillus spp. and Candida albicans (AJD 180) were investigated, using an
      agar diffusion method. Although both antifungal drugs showed a large inhibitory
      effect on C. albicans, oxiconazole had a very low inhibitory effect on
      Lactobacillus isolates. The natural resistance of lactobacilli to anti-fungal
      drugs may enable the development of an antifungal drug(s)/ probiotic combination
      for antifungal activity and lactobacilli replacement therapy.

PMID- 16086558
TI  - Treatment with granulocyte colony-stimulating factor for mobilization of bone
      marrow cells in patients with acute myocardial infarction.
AB  - BACKGROUND: This study was undertaken to evaluate the hypothesis that treatment
      with granulocyte colony-stimulating factor (G-CSF) to mobilize bone marrow cells
      (BMCs) is feasible and safe and promotes neovascularization and myocardial
      function in patients with acute myocardial infarction. METHODS: Fourteen patients
      in the treatment group and 9 patients in the control group were enrolled in this
      prospective, nonrandomized, open-label study. Forty-eight hours after successful
      recanalization and stent implantation, the patients of the treatment group
      received 10 microg/kg body weight per day G-CSF subcutaneously for mean treatment
      duration of 7.0 +/- 1.0 days. Nine patients fulfilled the entry criteria but
      refused participation and served therefore as control group. In both groups,
      regional wall motion and perfusion was evaluated with electrocardiogram-gated
      sestamibi single-photon emission computed tomography imaging and ejection
      fraction with radionuclidventriculography before discharge and after 3 months.
      RESULTS: No severe side effects of G-CSF treatment were observed. There was a
      significant improvement of the regional wall motion and perfusion within the
      treatment group (P < .0001) and between the treatment and control group (P < .05
      and P < .01, respectively). Ejection fraction in the treatment group increased
      from 0.40 +/- 0.11 to 0.48 +/- 0.13 (P < .01), whereas in the control group,
      ejection fraction increased from 0.40 +/- 0.13 to 0.43 +/- 0.13 (P = .049). A
      control angiography of the treatment group after 12.4 +/- 6.6 months showed an in
      stent restenosis in 1 patient. CONCLUSION: In patients with acute myocardial
      infarction, treatment with G-CSF to mobilize BMCs is feasible and safe and seems
      to be effective under clinical conditions. The therapeutic effect might be
      attributed to BMC-associated promotion of myocardial regeneration and
      neovascularization.

PMID- 16086559
TI  - Latin American randomized trial of balloon angioplasty versus coronary stenting
      in diabetic patients with small vessel reference size (Latin American Small
      Vessel [LASMAL II] Trial): immediate and long-term results.
AB  - Percutaneous coronary interventions (PCIs) in diabetic patients with small
      reference diameter vessels remain an important challenge in interventional
      cardiology because it is associated with increased complications and restenosis
      rates. Plain old balloon angioplasty (POBA) has limited efficacy in patients with
      lesions in small vessels. Although coronary stenting (stent) has been
      demonstrated to improve both immediate and long-term results after coronary
      intervention, small reference diameter is a strong predictor of restenosis after
      stent implantation. Thus, the question of how to best treat diabetic patients
      with lesions in small reference diameter remains unanswered. The purpose of this
      international and multicenter study was to compare the incidence of angiographic
      restenosis between percutaneous transluminal coronary angioplasty (PTCA) and
      stent in diabetic patients undergoing PCI of small reference diameter vessels
      using a specially designed phosphoryl choline (PC)-coated stent for small
      vessels. The patient population comprised of 220 diabetic patients with lesions
      in small reference diameter (< 2.9 mm but > 2.0 mm) that were randomized into two
      different PCI strategies: PTCA with provisional stenting (n = 109) versus stent
      (n = 111). In the PTCA arm, 26 patients (24%) crossed over to stent during the
      initial procedure; glycoproteins IIb to IIIa was used in 40.5% of patients in
      both groups. During initial procedure and at 30 days, both strategies of
      revascularitation had similar clinical success and acute complications. During
      long-term follow-up, even though requirements of target vessel revascularization
      and incidence of major adverse cardiovascular event were similar with both
      techniques, angiographic binary restenosis (45% with PTCA and 28% with stents, P
      = .047), net gain (0.74 mm with POBA and 0.94 mm with stents, P = .008), and
      freedom from target vessel failure (66% with POBA and 81.2% with stents, P =
      .013) were significantly improved when diabetic patients were initially treated
      with stent therapy. In summary, in diabetic patients with small coronary
      arteries, the use of a coronary PC coated stent as a primary device during
      percutaneous interventions was associated with better angiographic and long-term
      outcome.

PMID- 16086561
TI  - Arthroscopic excision of a painful bipartite patella fragment.
AB  - Bipartite patella, although usually asymptomatic, can become a source of
      persistent pain following injury. When nonoperative treatments such as
      physiotherapy and rest fail to produce any resolution in the symptoms, surgery is
      usually performed. This may include excision of the painful fragment, lateral
      retinacular release, or detachment of the vastus lateralis insertion, generally
      performed as open surgical procedures. In the case of vastus lateralis release,
      however, there has been recent report of statistically better results using an
      arthroscopic technique. Furthermore, open partial patellectomy has been
      criticized as being invasive and at times requiring long postoperative
      rehabilitation. We describe the case of a 26-year-old man who presented with a
      painful bipartite patella fragment that had not responded symptomatically to
      nonsurgical treatment. The painful fragment was removed arthroscopically as a day
      case under a general anesthetic. This was carried out through 3 portals and
      involved the use of a combination of probe, periosteal elevator, and arthroscopic
      shaver. Using this technique, we were able to minimize the surgical trauma
      associated with an open surgical procedure. The early result of this case
      encourages the use of an arthroscopic technique for partial patellectomy in the
      surgical treatment of a bipartite patella.

PMID- 16086560
TI  - Unsatisfactory clinical results of meniscal repair using the meniscus arrow.
AB  - PURPOSE: The all-inside technique using the Meniscus Arrow (Bionx Implants,
      Malvern, PA) has become a popular method for repairing meniscal tears. The few
      published clinical studies have been promising. The present study, with longer
      follow-up and larger numbers, does not show encouraging results. The clinical
      efficacy, failure rate, and associated complications of meniscal repair using the
      Meniscus Arrow with a minimum follow-up of 3 years are described. TYPE OF STUDY:
      Consecutive case series. METHODS: We studied 60 consecutive meniscal repairs in
      57 patients (average age, 27 years) using exclusively the Meniscus Arrow. Follow
      up averaged 54 months (range, 36 to 70 months). The anterior cruciate ligament
      (ACL) was intact in 12 knees (12 repairs), whereas 42 patients (45 repairs)
      underwent concomitant ACL reconstruction. One patient (2 repairs) had
      radiofrequency shrinkage of the ACL and another patient (1 repair) underwent
      concomitant arthroscopic fixation of a tibial eminence fracture. RESULTS:
      Seventeen of 60 repairs (28%) were documented as failures by repeat arthroscopy
      or magnetic resonance imaging; 5 of 12 repairs (42%) performed in knees with an
      intact ACL failed; and 9 of 45 menisci (20%) repaired in conjunction with an ACL
      reconstruction also failed. The remaining 3 failures occurred in knees with
      unsuccessful ACL procedures. The type of meniscus tear and the postoperative
      rehabilitation regimen were also factors that influenced the success rate in this
      study. Fifteen patients (26%) underwent a second operation because of persistent
      postoperative symptoms. One patient, whose repair failed, deferred a repeat
      operation after sustaining a postoperative pulmonary embolism. CONCLUSIONS:
      Contrary to previously published studies that reported good clinical results,
      this series revealed a 28% failure rate with significant postoperative
      complications, such as chondral scoring, fixator breakage, and postoperative
      joint-line irritation. This study has raised concerns about the continued liberal
      use of the Bionx Meniscus Arrow, leading the authors to abandon its use for
      repairing meniscal tears. LEVEL OF EVIDENCE: Level IV.

PMID- 16086562
TI  - Osteochondral allograft transplantation for treatment of glenohumeral
      instability.
AB  - The intimate contact between articular surfaces of the humeral head and glenoid
      labrum contribute to glenohumeral stability. When the articular surface area of
      these 2 surfaces is decreased, as with the presence of a bony Bankart lesion or
      an engaging Hill-Sachs lesion, the shoulder is more prone to dislocation.
      Although osteochondral allograft transplantation has become widely popular for
      the treatment of osteochondral defects of the knee, it is less used for treating
      bony defects of the humeral head. We present a case in which a 16-year-old male
      athlete with multiple anterior shoulder dislocations underwent arthroscopic
      repair of a Bankart lesion. His arthroscopic repair ultimately failed and on
      subsequent magnetic resonance imaging he was found to have a large, engaging Hill
      Sachs defect. He underwent arthroscopic osteochondral allograft transplantation
      to correct the humeral head bony deformity. As of the 1-year follow-up, the
      patient has had no recurrences and had returned to his normal level of activity.

PMID- 16086563
TI  - Autologous osteochondral transplantation for simple cyst in the patella.
AB  - Treatment options for chondral and osteochondral defects of the patella have been
      few and results have been inconsistent at best. Autologous osteochondral
      transplantation presents a new way to revisit these patellar defects. We report
      the case of a young female softball player with a simple cyst in the patella and
      an osteochondral defect that serves as the indication for autograft osteochondral
      transplantation.

PMID- 16086564
TI  - Fixation of a talar osteochondral fracture with cyanoacrylate glue.
AB  - Cyanoacrylate glue was invented by Ardis in 1949 and was first used in surgery in
      1959 by Coover. By further modifications, a nonhistotoxic form, butyl-2
      cyanoacrylate, which had strong tissue binding properties even in nondry
      environments, was developed. Its use in the fixation of fractures and osteotomies
      is still under investigation and has had promising results in treatment of
      craniofacial and mandibular injuries. We fixed a talar osteochondral fracture
      with cyanoacrylate. After 3 months, magnetic resonance imaging showed an
      anatomically reduced and intact chondral surface. The clinical result was
      excellent. We believe cyanoacrylate glue may form an alternative means of
      fixation for osteochondral and, possibly, for chondral fractures.

PMID- 16086565
TI  - The peashooter device: an invaluable tool for bone grafting during revision
      anterior cruciate ligament surgery.
AB  - Anterior cruciate ligament (ACL) reconstruction is a commonly performed surgery.
      Despite the improved technique and understanding of the rehabilitation rationale,
      the long-term success rate of good or excellent results is 75% to 90%. That
      leaves 10% to 25% of reconstructed ACLs with unsatisfactory results. Certainly,
      revision ACL surgery is not required in every patient. It should be
      individualized according to symptoms, objective findings, and the expectations of
      the patients. Revision of a failed ACL reconstruction may be carried out either
      as a single-stage procedure or a staged procedure. A staged procedure is
      recommended in cases of tunnel enlargement and/or removal of the implants and the
      failed graft, which leaves large bone defects. Bone grafting of the tibial bone
      tunnel defect is usually not a problem. On the other hand, grafting the femoral
      bone tunnel defect can present a challenge. It is important to place enough bone
      graft into the femoral tunnel securely and tightly so that bone incorporation
      takes place before the second-stage surgery, when the new tunnel can be drilled
      and the new ligament graft placed. We describe a simple technique using the
      elasticity and transparent properties of a chest drain, which effectively
      delivers the bone graft to the femoral tunnel defect. We name it the "peashooter
      device."

PMID- 16086566
TI  - Suture holes in anterior cruciate ligament bone-patellar tendon-bone grafts.
AB  - Anterior cruciate ligament reconstruction with a bone-patellar tendon-bone graft
      is a common and technically demanding surgery. Traditional preparation of the
      femoral bone plug includes 2 transcortical holes with leading sutures to pull the
      graft into the knee. The pull of the sutures and patellar tendon are not colinear
      with the bone plug and femoral socket. The bone plug tilts, thus impairing
      passage into the femoral socket. A new preparation technique was devised that, by
      changing the location of the suture holes, decreases graft tilting and improves
      passage. In our study, traditional and new techniques of femoral bone plug
      preparation were investigated by force diagramming and then graft modeling. Bone
      plug tilting was caused by the trailing pull of the patellar tendon eccentric to
      the plug and socket. By preparing the femoral bone plug with a diametric,
      transverse trailing suture hole, the plug became colinear with the femoral socket
      for easier passage. The new technique was then surgically implemented with
      straighter and faster graft passage.

PMID- 16086567
TI  - Development and application of an inside-to-out drill bit for anterior cruciate
      ligament reconstruction.
AB  - We report a novel drilling device for anterior cruciate ligament (ACL)
      reconstruction that has been developed. We invented a special inside-to-out drill
      bit that can make a bone socket in an inside-to-out fashion. A blade at the tip
      of a 4.5-mm diameter drill bit closes when the drill bit is in orthograde
      rotation, but the blade opens when the drill bit is in reverse rotation. The
      special drill bit is introduced into the joint through a 4.5-mm diameter bone
      tunnel rotating the bit in the orthograde direction. Then the drill bit is
      switched to reverse rotation and is pulled backward so that it bores the bone
      from the inside out. We have used this special drill bit in treating 31 ACL
      injured knees and have experienced no problems or complications with the
      procedure.

PMID- 16086568
TI  - Simple solution for failure of trailing sutures when using the EndoButton in
      anterior cruciate ligament reconstruction: the "Rescue Rein".
AB  - In this article, we introduce the technique of adding a second suture in the
      distal hole of the EndoButton. This suture, the "Rescue Rein," is kept with the
      graft and is a simple solution for recovering the graft during anterior cruciate
      ligament reconstruction when the EndoButton becomes jammed within the femoral
      tunnel and the trailing sutures cannot be removed.

PMID- 16086569
TI  - The HU knot: a new sliding knot for arthroscopic surgery.
AB  - Sliding knots are commonly used in arthroscopic knot tying. The Surgical knot as
      a hand-tied knot is very secure. We found that the Surgical knot could be used as
      a sliding knot. We have modified the Surgical knot to include a self-locking
      loop. A new sliding knot for arthroscopic surgery, the HU knot, is described. By
      tensioning the loop strand, the self-locking loop creates a snug knot without
      sliding backward. The HU knot provides great security.

PMID- 16086570
TI  - Suprascapular nerve block for shoulder arthroscopy.
AB  - The suprascapular nerve (SSN) originates from the C5 and C6 nerve roots and
      provides sensation for the posterior shoulder capsule, acromioclavicular joint,
      subacromial bursa, and coracoclavicular ligament. Blocking it provides pre
      emptive anesthesia, decreased intraoperative pain, and postoperative pain relief
      in shoulder arthroscopy. Under general anesthesia, 25 mL of 0.5% bupivacaine is
      injected by a spinal needle placed 1 cm medial to the convergence of the spine
      and clavicle, angling toward the coracoid. At a depth of 3 to 4 cm, the needle
      strikes the scapula body. The surgeon probes with the needle anteriorly until the
      scapula is no longer felt, then moves the needle back posteriorly until the bone
      is felt again. This places the needle at the coracoid base in the supraspinatus
      fossa where the SSN curves around the coracoid and heads to the glenohumeral
      joint. At this point, the anesthetic is injected, "flooding" the SSN location. In
      addition to the SSN block, other pain-control procedures should be performed,
      including bupivacaine injection of all portals and an intra-articular injection
      of morphine sulfate at the end of the procedure. The SSN block is an effective
      technique and can reduce postoperative medication needs and allow earlier patient
      discharge from the surgery center.

PMID- 16086571
TI  - Complete subscapularis tendon visualization and axillary nerve identification by
      arthroscopic technique.
AB  - The authors explain how one can view the greatest part of the subscapularis
      tendon from the subacromial aspect. From the articular aspect, it is possible to
      see only about one third of its entire surface. We also describe the standardized
      surgical technique used to obtain this visualization. To visualize the greatest
      possible surface of the tendon, it is necessary to make a trip to the subacromial
      space starting from the coracoacromial ligament, which leads us to the key
      structure: the coracoid. Having reached the coracoid, one goes further, following
      the conjoined tendon under which the subscapularis tendon is located. This last
      part of the trip takes place in a dark and potentially dangerous area because of
      its proximity to noble structures. In fact, the axillary nerve is easily
      identified on the way. Arthroscopic visualization of the greatest part of the
      subscapularis tendon is possible from the subacromial space. The technique is
      standard and follows a well-defined path. The exploration and conquest of this
      dark space through arthroscopy can open new frontiers both in knowledge and
      treatment.

PMID- 16086572
TI  - Arthroscopic treatment of acute and chronic acromioclavicular joint dislocation.
AB  - This article presents an all-arthroscopic technique for coracoclavicular ligament
      reconstruction by ligamentoplasty after acute or chronic acromioclavicular joint
      dislocation. A coracoacromial ligament transfer is done to reconstruct the torn
      coracoclavicular ligaments, similar to open surgery. The coracoacromial ligament
      is dissected from the undersurface of the acromion and is reinserted on the
      inferior clavicle by transosseous suture fixation. Additional wire or screw
      stabilization may be used. With this method, we achieve a very satisfactory
      reduction of the dislocated acromioclavicular joint.

PMID- 16086573
TI  - Fertility after B-Lynch suture and hypogastric artery ligation.
AB  - OBJECTIVE: To report a case of successful pregnancy after hypogastric artery
      ligation and the B-Lynch brace suturing technique. DESIGN: Case report. SETTING:
      Education and research hospital. PATIENT(S): A 22-year-old woman, whose first
      pregnancy was terminated by cesarean section owing to abruptio placenta and
      intrauterine fetal demise diagnosed at the 26th week of gestation, referred to
      our clinic for uterine atony. INTERVENTION(S): Hypogastric artery ligation and
      the B-Lynch brace suturing technique. MAIN OUTCOME MEASURE(S): Clinical pregnancy
      and live birth. RESULT(S): Two years after the surgery, the patient conceived
      spontaneously and delivered a healthy infant after an uneventful pregnancy.
      CONCLUSION(S): This is the first reported case of successful pregnancy after
      hypogastric artery ligation and B-Lynch suturing technique. This life-saving
      therapeutic option for severe postpartum hemorrhage appears to be a safe
      procedure that does not impair subsequent fertility and pregnancy outcomes. The B
      Lynch suturing technique seems to be simple and has the capability of preserving
      the uterus; therefore it may be considered as the first-line surgical treatment
      for uterine atony before considering hysterectomy.

PMID- 16086574
TI  - Maternal and female fetal virilization caused by pregnancy luteomas.
AB  - OBJECTIVE: To present the maternal and female fetal virilization caused by
      excessive androgen secretion of pregnancy luteomas. DESIGN: Case report. SETTING:
      University-based teaching hospital. PATIENT(S): A nulligravida woman suffering
      from bilateral hydronephrosis and recurrent acute pyelonephritis caused by
      bilateral solid ovarian tumors presented virilization during the third trimester.
      Without prompt surgical intervention, the maternal hyperandrogenemia returned to
      a normal level and regression of bilateral ovarian tumors occurred spontaneously
      after a female fetus with clitoral hypertrophy and temporal hyperandrogenemia was
      delivered. In spite of lacking histology, the clinical course is compared to that
      of pregnancy luteomas. INTERVENTION(S): Noninvasive imaging assessment. MAIN
      OUTCOME MEASURE(S): Maternal and female fetal virilization. RESULT(S): Regression
      of androgen-secreting pregnancy luteomas and hyperandrogenism during the
      puerperium but apparent female fetal clitoral hypertrophy. CONCLUSION(S): The
      maternal and female fetal virilization was caused by exaggerating androgen
      secretion of bilateral ovarian solid tumors. Spontaneous regression of ovarian
      tumors and hyperandrogenemia during the puerperium is the natural course of
      pregnancy luteomas, not true neoplasms.

PMID- 16086575
TI  - Stabilization and regression of a recurrent desmoid tumor with the antiestrogen
      toremifene.
AB  - OBJECTIVE: To report a case of a pelvic desmoid tumor that was treated with the
      antiestrogen toremifene after a failed attempt at surgical excision. DESIGN: Case
      report. SETTING: University reproductive endocrine practice. PATIENT(S): A
      reproductive-aged woman with a recurrent desmoid tumor. INTERVENTION(S): After
      surgical excision of a desmoid tumor that presented during childbirth, subsequent
      recurrence resulted in the use of toremifene for tumor stabilization. MAIN
      OUTCOME MEASURE(S): Magnetic resonance imaging was used to monitor desmoid tumor
      size. RESULT(S): One year after postsurgical recurrence of the desmoid tumor, the
      patient began treatment with the antiestrogen toremifene. Tumor stabilization and
      regression with symptomatic relief was observed. Nine years of antiestrogen use
      revealed no progression in tumor size or patient symptoms. After the patient
      demonstrated perimenopausal symptoms, toremifene administration was discontinued
      without a return of symptoms or tumor growth after 3 years. CONCLUSION(S): Our
      case demonstrates that toremifene is a safe and effective therapy that can be
      used for the stabilization and regression of desmoid tumors. An antiestrogen
      should be considered as adjuvant therapy after surgery and as a first-line
      treatment with disease recurrence. Discontinuation of antiestrogen therapy was
      shown to be done safely after the patient started to show signs of decreased
      endogenous estrogen production.

PMID- 16086576
TI  - Safe resectoscopic evacuation of a 10-week viable cervical pregnancy after
      transfemoral bilateral uterine artery embolization.
AB  - OBJECTIVE: To describe therapy of a 10.5-week viable cervical pregnancy. DESIGN:
      Case report. SETTING: An academic medical center. PATIENT(S): A 38-year-old women
      with cervical pregnancy. INTERVENTION(S): Transfemoral bilateral uterine artery
      embolization followed by resectoscopic evacuation of the gestational products.
      MAIN OUTCOME MEASURE(S): Resolution of products of conception and serum beta-hCG
      levels. RESULT(S): Successful outcome with minimal maternal morbidity and
      preservation of the uterus. CONCLUSION(S): Uterine artery embolotherapy followed
      by resectoscopic evacuation of cervical pregnancy minimized morbidity and
      preserved the uterus.

PMID- 16086577
TI  - Foldamers with hybrid biological and synthetic sequences as selective DNA
      fluorescent probes.
AB  - Foldable polymers with alternating single-strand deoxyribonucleic acid (ssDNA)
      and planar fluorescent organic chromophores can self-organize into folded
      nanostructures and hence are hybrid foldamers with biological sequences and
      synthetic properties. The biological sequence provides highly specific molecular
      recognition properties, while the physical properties of synthetic chromophores
      offer sensitive fluorescence detection. In this paper, we describe that rational
      designed hybrid foldamers exhibit potential in the detection of polynucleotides.
      Under strictly controlled laboratory conditions, fluorescence measurements
      indicate that configuration change due to binding of polynucleotides with one or
      two mismatched bases can be readily distinguished. These results shed light on
      the design and construction of nanostructured foldamers with actuator and sensory
      properties, which may find important applications as biological probes.

PMID- 16086578
TI  - Structural basis for antagonism by suramin of heparin binding to vaccinia
      complement protein.
AB  - Suramin is a competitive inhibitor of heparin binding to many proteins, including
      viral envelope proteins, protein tyrosine phosphatases, and fibroblast growth
      factors (FGFs). It has been clinically evaluated as a potential therapeutic in
      treatment of cancers caused by unregulated angiogenesis, triggered by FGFs.
      Although it has shown clinical promise in treatment of several cancers, suramin
      has many undesirable side effects. There is currently no experimental structure
      that reveals the molecular interactions responsible for suramin inhibition of
      heparin binding, which could be of potential use in structure-assisted design of
      improved analogues of suramin. We report the structure of suramin, in complex
      with the heparin-binding site of vaccinia virus complement control protein (VCP),
      which interacts with heparin in a geometrically similar manner to many FGFs. The
      larger than anticipated flexibility of suramin manifested in this structure, and
      other details of VCP-suramin interactions, might provide useful structural
      information for interpreting interactions of suramin with many proteins.

PMID- 16086579
TI  - Helix switching of a key active-site residue in the cytochrome cbb3 oxidases.
AB  - In the respiratory chains of mitochondria and many aerobic prokaryotes, heme
      copper oxidases are the terminal enzymes that couple the reduction of molecular
      oxygen to proton pumping, contributing to the protonmotive force. The cbb(3)
      oxidases belong to the superfamily of enzymes that includes all of the heme
      copper oxidases. Sequence analysis indicates that the cbb(3) oxidases are missing
      an active-site tyrosine residue that is absolutely conserved in all other known
      heme-copper oxidases. In the other heme-copper oxidases, this tyrosine is known
      to be subject to an unusual post-translational modification and to play a
      critical role in the catalytic mechanism. The absence of this tyrosine in the
      cbb(3) oxidases raises the possibility that the cbb(3) oxidases utilize a
      different catalytic mechanism from that of the other members of the superfamily.
      Using homology modeling, quantum chemistry, and molecular dynamics, a model of
      the structure of subunit I of a cbb(3) oxidase (Vibrio cholerae) was constructed.
      The model predicts that a tyrosine residue structurally analogous to the active
      site tyrosine in other oxidases is present in the cbb(3) oxidases but that the
      tyrosine originates from a different transmembrane helix within the protein. The
      predicted active-site tyrosine is conserved in the sequences of all of the known
      cbb(3) oxidases. Mutagenesis of the tyrosine to phenylalanine in the V. cholerae
      oxidase resulted in a fully assembled enzyme with nativelike structure but
      lacking catalytic activity. These findings strongly suggest that all of the heme
      copper oxidases utilize the same catalytic mechanism and provide an unusual
      example in which a critical active-site residue originates from different places
      within the primary sequence for different members of the same superfamily.

PMID- 16086580
TI  - Reconstitution of a defunct glycolytic pathway via recruitment of ambiguous sugar
      kinases.
AB  - During a recent investigation of the persistence of substrate ambiguity in
      contemporary enzymes, we identified three distinct ambiguous sugar kinases
      embedded within the modern Escherichia coli genome [Miller, B. G., and Raines, R.
      T. (2004) Biochemistry 43, 6387-6392]. These catalysts are the YajF, YcfX, and
      NanK polypeptides, all of which possess rudimentary glucokinase activities. Here,
      we report on the discovery of a fourth bacterial kinase with ambiguous substrate
      specificity. AlsK phosphorylates the glucose epimer, d-allose, with a k(cat)/K(m)
      value of 6.5 x 10(4) M(-)(1) s(-)(1). AlsK also phosphorylates d-glucose, with a
      k(cat)/K(m) value that is 10(5)-fold lower than the k(cat)/K(m) value displayed
      by native E. coli glucokinase. Overexpression of the alsK gene relieves the
      auxotrophy of a glucokinase-deficient bacterium, demonstrating that weak
      enzymatic activities derived from ambiguous catalysts can provide organisms with
      elaborated metabolic capacities. To explore how ambiguous catalysts are recruited
      to provide new functions, we placed the glucokinase-deficient bacterium under
      selection for growth at the expense of glucose. Under these conditions, the
      bacterium acquires a spontaneous mutation in the putative promoter region of the
      yajF gene, a locus previously shown to encode a sugar kinase with relaxed
      substrate specificity. The point mutation regenerates a consensus sigma(70)
      promoter sequence that leads to a 94-fold increase in the level of yajF
      expression. This increase provides sufficient glucokinase activity for
      reconstitution of the defunct glycolytic pathway of the bacterial auxotroph. Our
      current findings indicate that ambiguous enzymatic activities continue to play an
      important role in the evolution of new metabolic pathways, and provide insight
      into the molecular mechanisms that facilitate the recruitment of such catalysts
      during periods of natural selection.

PMID- 16086581
TI  - Functional interactions of Raf and MEK with Jun-N-terminal kinase (JNK) result in
      a positive feedback loop on the oncogenic Ras signaling pathway.
AB  - In previous studies we have found that oncogenic (Val 12)-ras-p21 induces Xenopus
      laevis oocyte maturation that is selectively blocked by two ras-p21 peptides, 35
      47, also called PNC-7, that blocks its interaction with raf, and 96-110, also
      called PNC-2, that blocks its interaction with jun-N-terminal kinase (JNK). Each
      peptide blocks activation of both JNK and MAP kinase (MAPK or ERK) suggesting
      interaction between the raf-MEK-ERK and JNK-jun pathways. We further found that
      dominant negative raf blocks JNK induction of oocyte maturation, again suggesting
      cross-talk between pathways. In this study, we have undertaken to determine where
      these points of cross-talk occur. First, we have immunoprecipitated injected Val
      12-Ha-ras-p21 from oocytes and found that a complex forms between ras-p21 raf,
      MEK, MAPK, and JNK. Co-injection of either peptide, but not a control peptide,
      causes diminished binding of ras-p21, raf, and JNK. Thus, one site of interaction
      is cooperative binding of Val 12-ras-p21 to raf and JNK. Second, we have injected
      JNK, c-raf, and MEK into oocytes alone and in the presence of raf and MEK
      inhibitors and found that JNK activation is independent of the raf-MEK-MAPK
      pathway but that activated JNK activates raf, allowing for activation of ERK.
      Furthermore, we have found that constitutively activated MEK activates JNK. We
      have corroborated these findings in studies with isolated protein components from
      a human astrocyte (U-251) cell line; that is, JNK phosphorylates raf but not the
      reverse; MEK phosphorylates JNK but not the reverse. We further have found that
      JNK does not phosphorylate MAPK and that MAPK does not phosphorylate JNK. The
      stress-inducing agent, anisomycin, causes activation of JNK, raf, MEK, and ERK in
      this cell line; activation of JNK is not inhibitable by the MEK inhibitor, U0126,
      while activation of raf, MEK, and ERK are blocked by this agent. These results
      suggest that activated JNK can, in turn, activate not only jun but also raf that,
      in turn, activates MEK that can then cross-activate JNK in a positive feedback
      loop.

PMID- 16086582
TI  - Modulation of the membrane orientation and secondary structure of the C-terminal
      domains of Bak and Bcl-2 by lipids.
AB  - Infrared spectroscopy was used to study the secondary structure of peptides which
      imitate the amino acid sequences of the C-terminal domains of the pro-apoptotic
      protein Bak (Bak-C) and the anti-apoptotic protein Bcl-2 (Bcl-2-C) when
      incorporated into different lipid vesicles. Whereas beta-pleated sheet was the
      predominant type of secondary structure of Bak-C in the absence of membranes, the
      same peptide adopted different structures depending on lipid composition when
      incorporated into membranes, with the predominance of the alpha-helical structure
      in the case of DMPC and other phospholipids, such as POPC and POPG. However, beta
      pleated sheet was the predominant structure in other membranes containing
      phospholipids with longer fatty acyl chains and cholesterol, as well as in a
      mixture which imitates the composition of the outer mitochondrial membrane (OMM).
      Similarly, Bcl-2-C adopted a structure with a predominance of intermolecularly
      bound pleated beta-sheet in the absence of membranes, with alpha-helix as the
      main component in the presence of DMPC and POPG, but intermolecular beta-sheet in
      the presence of EYPC and cholesterol. Using ATR-IR, it was found that the
      orientation of the alpha-helical components of both domains was nearly
      perpendicular to the plane of the membrane in the presence of DMPC membranes, but
      not in EYPC or OMM membranes. (2)H NMR spectroscopy of DMPC-d(54) confirmed the
      transmembrane disposition of the domains, revealing that they broadened the phase
      transition temperature, although the order parameter of the C-D bonds was not
      affected, as might have been expected for intrinsic peptides. When all these
      results are taken together, it was concluded that the domains only form
      transmembrane helices in membranes of reduced thickness and that hydrophobic
      mismatching occurs in thicker membranes, as happens in the membrane imitating the
      composition of the OMM, where the peptides were partially located outside the
      membranes.

PMID- 16086583
TI  - Amino-terminally truncated Abeta peptide species are the main component of cotton
      wool plaques.
AB  - Cotton wool plaques (CWPs) are round lesions that lack a central amyloid core.
      CWPs have been observed in individuals affected by early-onset familial Alzheimer
      disease (FAD) associated with mutations in the presenilin 1 (PSEN1) gene. Here we
      present the characterization of the amyloid-beta (Abeta) peptides deposited in
      the brain of an individual affected by FAD carrying the novel missense (V261I)
      mutation in the PSEN1 gene. Matrix-assisted laser desorption ionization time-of
      flight mass spectrometry was used to determine the Abeta peptide species present
      in the cerebral and cerebellar cortices, in leptomeningeal vessels, and in CWPs
      isolated by laser microdissection (LMD). Our results indicate that amino
      terminally truncated Abeta peptide species ending at residues 42 and 43 are the
      main Abeta peptides deposited in brain parenchyma and LMD-CWPs in association
      with the PSEN1 V261I mutation. Full-length Abeta1-42 and Abeta1-43 peptide
      species were underrepresented. CWPs were not found to be associated with vessels
      and did not contain Abeta1-40 peptides, the main component of the vascular
      deposits. Although Abeta deposits were present mostly in the form of CWPs in the
      cerebral cortex and as diffuse deposits in the cerebellar cortex, a similar array
      of amino-terminally truncated Abeta peptide species was seen in both cases. The
      biochemical data support the concept that parenchymal and vascular amyloid
      deposits are associated with a different array of Abeta peptide species. The
      generation and parenchymal deposition of highly insoluble amino-terminally
      truncated Abeta peptides may play an important role in the pathogenesis of AD and
      must be taken into consideration in developing new diagnostic and therapeutic
      strategies.

PMID- 16086584
TI  - Binding of madindoline A to the extracellular domain of gp130.
AB  - Elevated levels of IL-6 and IL-11 are associated with multiple myeloma,
      rheumatoid arthritis, hypercalcemia, cancer cachexia, and Castleman's disease.
      Madindoline A (MadA), isolated from Streptomyces nitrosporeus K93-0711,
      specifically inhibits the growth of IL-6- and IL-11-dependent cell lines, most
      likely by interfering with the homodimerization of gp130. This raises the
      possibility that MadA can be used as a model compound for the development of
      novel chemotherapeutic agents. In this report, we demonstrate that the binding of
      MadA to gp130 is specific and noncovalent, and displays a relatively low
      affinity. Furthermore, we show that the tricyclic 3a-hydroxytetrahydrofuro[2,3
      b]indole (HFI) moiety of MadA alone is not sufficient for binding. Matrix-bound
      MadA precipitates a protein composed of the extracellular domain of gp130 fused
      to the Fc region of the immunoglobulin heavy chain. Binding is inhibited in a
      dose-dependent manner by preincubation with free MadA. The K(D) for binding of
      MadA to gp130 is 288 microM, as determined by surface plasmon resonance (SPR)
      based biosensor analysis. The HFI portion of MadA does not bind to gp130 in
      either affinity precipitation or SPR analyses. Finally, MadA, but not the HFI
      portion, inhibits IL-6-dependent Stat3 tyrosine phosphorylation in HepG2 cells.

PMID- 16086585
TI  - Formation of a long-lived photoproduct with a deprotonated Schiff base in
      proteorhodopsin, and its enhancement by mutation of Asp227.
AB  - Proteorhodopsin, a retinal protein of marine proteobacteria similar to
      bacteriorhodopsin of the archaea, is a light-driven proton pump. Absorption of a
      light quantum initiates a reaction cycle (turnover time of ca. 50 ms), which
      includes photoisomerization of the retinal from the all-trans to the 13-cis form
      and transient deprotonation of the retinal Schiff base, followed by recovery of
      the initial state. We report here that in addition to this fast cyclic
      conversion, illumination at high pH results in accumulation of a long-lived
      photoproduct absorbing at 362 nm. This photoconversion is much more efficient in
      the D227N mutant in which the anionic Asp227, which together with Asp97
      constitutes the Schiff base counterion, is replaced with a neutral residue. Upon
      illumination at pH 8.5, most of the D227N pigment is converted to the 362 nm
      species, with a quantum efficiency of ca. 0.2. The pK(a) for this transition in
      the wild type is 9.6, but decreased to 7.5 after mutation of Asp227. The short
      wavelength of the absorption maximum of the photoproduct indicates that it has a
      deprotonated Schiff base. In the dark, this photoproduct is converted back to the
      initial pigment with a time constant of 30 min (in D227N, at pH 8.5), but it can
      be reconverted more rapidly by illumination with near-UV light. Experiments with
      "locked" retinal analogues which selectively exclude rotation around either the
      C9=C10, C11=C12, or C13=C14 bond show that formation of the 362 nm species
      involves isomerization around the C13=C14 bond. In agreement with this, retinal
      extraction indicates that the 362 nm photoproduct is 13-cis whereas the initial
      state is predominantly all-trans. A rapid shift of the pH from 8.5 to 4 greatly
      accelerates thermal reconversion of the 362 nm species to the initial pigment,
      suggesting that its recovery involving the thermal isomerization of the
      chromophore is controlled by ionizable residues, primarily the Schiff base and
      Asp97. The transformation to the long-lived 362 nm photoproduct is apparently a
      side reaction of the photocycle, a response to high pH, caused by alteration of
      the normal reprotonation and reisomerization pathway of the Schiff base.

PMID- 16086586
TI  - Aromatase reaction of 3-deoxyandrogens: steric mode of the C-19 oxygenation and
      cleavage of the C10-C19 bond by human placental aromatase.
AB  - Aromatase is a cytochrome P-450 enzyme complex that catalyzes the conversion of
      androst-4-ene-3,17-dione (AD) to estrone and formic acid through three sequential
      oxygenations of the 19-methyl group. To gain insight into the catalytic function
      of aromatase as well as the mechanism of the hitherto uncertain third oxygenation
      step, we focused on the aromatase-catalyzed 19-oxygenation of 3-deoxyandrogens: 3
      deoxy-AD (1), which is a very powerful competitive inhibitor but poor substrate
      of aromatase, and its 5-ene isomer 4, which is a good competitive inhibitor and
      effective substrate of the enzyme. In incubations of their 19S-(3)H-labeled 19
      hydroxy derivatives 2 and 5 and the corresponding 19R-(3)H isomers with human
      placental microsomes in the presence of NADPH under air, the radioactivity was
      liberated in both water and formic acid. The productions of (3)H(2)O and (3)HCOOH
      were blocked by the substrate AD or the inhibitor 4-hydroxy-AD, indicating that
      these productions are due to a catalytic function of aromatase. A comparison of
      the (3)H(2)O production from S-(3)H substrates 2 and 5 with that from the
      corresponding R-(3)H isomers revealed that the 19-pro-R hydrogen atom was
      stereospecifically (pro-R:pro-S = 100:0) removed in the conversion of 5-ene
      substrate 5 into the 19-oxo product 6, whereas 75:25 stereoselectivity for the
      loss of the pro-R and pro-S hydrogen atoms was observed in the oxygenation of the
      other substrate, 2. The present results reveal that human placental aromatase
      catalyzes three sequential oxygenations at C-19 of 3-deoxyandrogens 1 and 4 to
      cause the cleavage of the C(10)-C(19) bond through their 19-hydroxy (2 and 5) and
      19-oxo (3 and 6) intermediates, respectively, where there is a difference in the
      stereochemistry between the two androgens in the second 19-hydroxylation. It is
      implied that the aromatase-catalyzed 19-oxygenation of 5-ene steroid 4 but not
      the 4-ene isomer 1 would proceed in the same steric mechanism as that involved in
      the AD aromatization.

PMID- 16086587
TI  - Aggregates of the chlorophyll-binding protein IsiA (CP43') dissipate energy in
      cyanobacteria.
AB  - In many natural habitats, growth of cyanobacteria may be limited by a low
      concentration of iron. Cyanobacteria respond to this condition by expressing a
      number of iron-stress-inducible genes, of which the isiA gene encodes a
      chlorophyll-binding protein known as IsiA or CP43'. IsiA monomers assemble into
      ring-shaped polymers that encircle trimeric or monomeric photosystem I (PSI), or
      are present in supercomplexes without PSI, in particular upon prolonged iron
      starvation. In this report, we present steady-state and time-resolved
      fluorescence measurements of isolated IsiA aggregates that have been purified
      from an iron-starved psaFJ-minus mutant of Synechocystis PCC 6803. We show that
      these aggregates have a fluorescence quantum yield of approximately 2% compared
      to that of chlorophyll a in acetone, and that the dominating fluorescence
      lifetimes are 66 and 210 ps, more than 1 order of magnitude shorter than that of
      free chlorophyll a. Comparison of the temperature dependence of the fluorescence
      yields and spectra of the isolated aggregates and of the cells from which they
      were obtained suggests that these aggregates occur naturally in the iron-starved
      cells. We suggest that IsiA aggregates protect cyanobacterial cells against the
      deleterious effects of light.

PMID- 16086588
TI  - Substrate discrimination by the human GTP fucose pyrophosphorylase.
AB  - GTP-l-fucose pyrophosphorylase (GFPP, E. C. 2.7.7.30) catalyzes the reversible
      condensation of guanosine triphosphate and beta-l-fucose-1-phosphate to form the
      nucleotide-sugar GDP-beta-l-fucose. The enzyme functions primarily in the
      mammalian liver and kidney to salvage free l-fucose during the breakdown of
      glycolipids and glycoproteins. The mechanism by which this protein discriminates
      between substrate and nonsubstrate molecules has been elucidated for the first
      time in this study. The ability of GFPP to form nucleotide-sugars from a series
      of base-, ribose-, phosphate-, and hexose-modified precursor molecules has
      revealed that the enzyme active site senses a series of substrate substituents
      that drive substrate/nonsubstrate discrimination. These substituents alter the
      ability of the precursor molecule to interact with the enzyme, as measured by
      either changes in the Michaelis constant, K(m), the binding affinity, K(a), or
      through changes in enzymatic turnover, k(cat). In this work, the combined
      substrate binding and enzyme analysis has revealed that the nature of the purine
      base is the major determinant in substrate specificity, followed by the nature of
      the hexose-1-P, and finally by the ribose moiety. Binding is enthalpy-driven and
      does not involve proton transfer. For the majority of nucleotide-sugar analogues,
      binding to GFPP is entropically unfavorable; however, surprisingly, a few of the
      substrate analogues tested bind to GFPP with a favorable entropic term.

PMID- 16086589
TI  - Enzymes of the last steps of chlorophyll biosynthesis: modification of the
      substrate structure helps to understand the topology of the active centers.
AB  - Enzymes catalyzing two of the late steps of chlorophyll biosynthesis are
      NADPH:protochlorophyllide oxidoreductase (POR), responsible for the light
      dependent reduction of protochlorophyllide to chlorophyllide, and chlorophyll
      synthase that catalyses the esterification of chlorophyllide to chlorophyll.
      Inhibitors of these enzymes are of interest as potential herbicides. Both enzymes
      presumably form a complex, and the question arose whether chlorophyll synthase
      can react with chlorophyllide while it is still bound to POR. Here, we describe
      the chemical modification of protochlorophyllides and chlorophyllides with space
      filling substituents at rings A, B, and E of the tetrapyrrole macrocycle and the
      reactivity of the modified substrates. Both enzymes tolerate the large and
      flexible phenylamino substituent at ring B, indicating that ring B points toward
      the enzyme surface while the substrate is bound. On the basis of the standard
      compound zinc protopheophorbide a (100% activity), the 7(1)-phenylamino
      derivative shows a comparable activity (83%) with POR that is higher than that of
      the parent formyl derivative zinc protopheophorbide b (58% activity). In
      contrast, the 3(1)-phenylamino derivative is less active (12%) than the parent
      formyl compound zinc protopheophorbide d (49% activity), indicating that the
      binding pocket leaves less space around ring A than around ring B. Almost no
      space must be left around ring E because substitution of the 13(2)-carboxymethyl
      ester (100% activity) by the 13(2)-carboxyethyl ester reduces the activity to
      0.2%. Chlorophyll synthase leaves somewhat more space around ring E on the A side
      of the tetrapyrrole in the binding pocket; substitution of the 13(2)-proton (100%
      activity) by a methoxy group (53% activity) and an ethoxy group (11% activity) is
      tolerated to a certain extent, while the carbomethoxy group in this position is
      not accepted. Opening of ring E to a chlorin e6 dimethylester is tolerated (39%
      activity), while the large benzylamide residue at this site leads to the loss of
      activity. We conclude that the tetrapyrroles bind to both enzymes in the same
      direction: rings C, D, and E are oriented to the interior of the binding cleft,
      and rings A and B are oriented to the surface of the enzyme; this excludes
      simultaneous binding to both enzymes.

PMID- 16086590
TI  - Thermodynamic stability of RNA structures formed by CNG trinucleotide repeats.
      Implication for prediction of RNA structure.
AB  - Trinucleotide repeat expansion diseases (TREDs) are correlated with elongation of
      CNG DNA and RNA repeats to pathological level. This paper shows, for the first
      time, complete data concerning thermodynamic stabilities of RNA with CNG
      trinucleotide repeats. Our studies include the stability of oligoribonucleotides
      composed of two to seven of CAG, CCG, CGG, and CUG repeats. The thermodynamic
      parameters of helix propagation correlated with the presence of multiple N-N
      mismatches within CNG RNA duplexes were also determined. Moreover, the total
      stability of CNG RNA hairpins, as well as the contribution of trinucleotide
      repeats placed only in the stem or loop regions, was evaluated. The improved
      thermodynamic parameters allow to predict much more accurately the thermodynamic
      stabilities and structures of CNG RNAs.

PMID- 16086591
TI  - Reversible equilibrium unfolding of triosephosphate isomerase from Trypanosoma
      cruzi in guanidinium hydrochloride involves stable dimeric and monomeric
      intermediates.
AB  - The reversible guanidinium hydrochloride-induced unfolding of Trypanosoma cruzi
      triosephosphate isomerase (TcTIM) was characterized under equilibrium conditions.
      The catalytic activity was followed as a native homodimeric functional probe.
      Circular dichroism, intrinsic fluorescence, and size-exclusion chromatography
      were used as secondary, tertiary, and quaternary structural probes, respectively.
      The change in ANS fluorescence intensity with increasing denaturant
      concentrations was also determined. The results show that two stable
      intermediates exist in the transition from the homodimeric native enzyme to the
      unfolded monomers: one (N(2*)) is a slightly more expanded, non-native, and
      active dimer, and the other is a partially expanded monomer (M) that binds ANS.
      Spectroscopic and activity data were used to reach a thermodynamic
      characterization. The results indicate that the Gibbs free energies for the
      partial reactions are 4.5 (N(2) <==> N(2*)), 65.8 (N(2*) <==> 2M), and 17.8
      kJ/mol (M <==> U). It appears that TcTIM monomers are more stable than those
      found for other TIM species (except yeast TIM), where monomer stability is only
      marginal. These results are compared with those for the guanidinium hydrochloride
      induced denaturation of TIM from different species, where despite the functional
      and three-dimensional similarities, a remarkable heterogeneity exists in the
      unfolding pathways.

PMID- 16086592
TI  - Oligomerization of the human ABC transporter ABCG2: evaluation of the native
      protein and chimeric dimers.
AB  - Human ABCG2, a member of the ATP binding cassette (ABC) transporter superfamily,
      is overexpressed in numerous multidrug-resistant cells in culture. Localized to
      the plasma membrane, ABCG2 contains six transmembrane segments and one nucleotide
      binding domain (NBD) and is thought to function as a dimer or higher order
      oligomer. Chimeric fusion proteins containing two ABCG2 proteins joined either
      with or without a flexible linker peptide were expressed at the plasma membrane
      and maintained drug transport activity. Expression of an ABCG2 variant mutated in
      a conserved residue in the Walker B motif of the NBD (D210N) resulted in a non
      functional protein expressed at the cell surface. Expression of an ABCG2 chimeric
      dimer containing the D210N mutation in the first ABCG2 resulted in a dominant
      negative phenotype, as the protein was expressed at the surface but was not
      functional. Using a bifunctional photoaffinity nucleotide analogue and a non
      membrane-permeable cysteine-specific chemical cross-linking agent, a dimer is the
      predominant form of oligomerized ABCG2 under our assay conditions. Furthermore,
      these experiments demonstrated that the dimer interface includes, but may not be
      limited to, interactions between residues in each monomeric NBD and separate
      disulfide interactions between the cysteines in the third extracellular loop of
      each monomer. By changing all three extracellular cysteines to alanine, we showed
      that although extracellular disulfide bonds may exist between monomers, they are
      not essential for ABCG2 localization, transport activity, or prazosin-stimulated
      ATPase activity. Together, these data suggest that ABCG2 functions as a dimer,
      but do not exclude functional higher order oligomers.

PMID- 16086593
TI  - Allosterism in membrane binding: a common motif of the annexins?
AB  - Annexins are a family of proteins generally described as Ca(2+)-dependent for
      phospholipid binding. Yet, annexins have a wide variety of binding behaviors and
      conformational states, some of which are lipid-dependent and Ca(2+)-independent.
      We present a model that captures the cation and phospholipid binding behavior of
      the highly conserved core of the annexins. Experimental data for annexins A4 and
      A5, which have short N-termini, were globally modeled to gain an understanding of
      how the lipid-binding affinity of the conserved protein core is modulated.
      Analysis of the binding behavior was achieved through use of the lanthanide
      Tb(3+) as a Ca(2+) analogue. Binding isotherms were determined experimentally
      from the quenching of the intrinsic fluorescence of annexins A4 and A5 by Tb(3+)
      in the presence or absence of membranes. In the presence of lipid, the affinity
      of annexin for cation increases, and the binding isotherms change from hyperbolic
      to weakly sigmoidal. This behavior was modeled by isotherms derived from
      microscopic binding partition functions. The change from hyperbolic to sigmoidal
      binding occurs because of an allosteric transition from the annexin solution
      state to its membrane-associated state. Protein binding to lipid bilayers renders
      cation binding by annexins cooperative. The two annexin states denote two
      affinities of the protein for cation, one in the absence and another in the
      presence of membrane. In the framework of this model, we discuss membrane binding
      as well as the influence of the N-terminus in modifying the annexin cation
      binding affinity by changing the probability of the protein to undergo the
      postulated two-state transition.

PMID- 16086594
TI  - The acute phase protein haptoglobin is a mammalian extracellular chaperone with
      an action similar to clusterin.
AB  - Haptoglobin (Hp) is an acidic glycoprotein present in most body fluids of humans
      and other mammals. Although the functions of Hp are not yet fully understood, the
      available evidence indicates that it is likely to play an important role in
      suppressing inflammatory responses. Some earlier work suggested that Hp might be
      a newly identified member of a small group of extracellular chaperones found at
      significant levels in human body fluids. Previously, the only well-characterized
      member of this group was clusterin, which shares functional similarities with the
      small heat-shock proteins. We report here that Hp specifically inhibited the
      precipitation of a variety of proteins induced by either heat or oxidation,
      including proteins in unfractionated human serum. We also show that, like
      clusterin, Hp (i) inhibits the precipitation of stressed proteins by forming
      solubilized high molecular weight complexes with them, (ii) cannot protect
      enzymes from heat-induced loss of function, and (iii) lacks ATPase activity and
      the ability to independently refold proteins following stresses. Furthermore, we
      show that Hp has maximum chaperone activity at mildly alkaline pH and, unlike
      clusterin, does not undergo significant changes in oligomerization state
      coincident with pH-induced changes in chaperone activity. Our results raise the
      possibility that Hp may exert an anti-inflammatory action in vivo by inhibiting
      the inappropriate self-association of "damaged" (misfolded) extracellular
      proteins.

PMID- 16086595
TI  - Two-dimensional measurement of proton T1rho relaxation in unlabeled proteins:
      mobility changes in alpha-bungarotoxin upon binding of an acetylcholine receptor
      peptide.
AB  - A method for the measurement of proton T(1)(rho) relaxation times in unlabeled
      proteins is described using a variable spin-lock pulse after the initial
      nonselective 90 degrees excitation in a HOHAHA pulse sequence. The experiment is
      applied to alpha-bungarotoxin (alpha-BTX) and its complex with a 25-residue
      peptide derived from the acetylcholine receptor (AChR) alpha-subunit. A good
      correlation between high T(1)(rho) values and increased local motion is revealed.
      In the free form, toxin residues associated with receptor binding according to
      the NMR structure of the alpha-BTX complex with an AChR peptide and the model for
      alpha-BTX with the AChR [Samson, A. O., et al. (2002) Neuron 35, 319-332] display
      high mobility. When the AChR peptide binds, a decrease in the relaxation times
      and the level of motion of residues involved in binding of the receptor alpha
      subunit is exhibited, while residues implicated in binding gamma- and delta
      subunits retain their mobility. In addition, the quantitative T(1)(rho)
      measurements enable us to corroborate the mapping of boundaries of the AChR
      determinant strongly interacting with the toxin [Samson, A. O., et al. (2001)
      Biochemistry 40, 5464-5473] and can similarly be applied to other protein
      complexes in which peptides represent one of the two interacting proteins. The
      presented method is advantageous because of its simplicity, generality, and time
      efficiency and paves the way for future investigation of proton relaxation rates
      in small unlabeled proteins.

PMID- 16086596
TI  - Targeting the distal lung in asthma: do inhaled corticosteroids treat all areas
      of inflammation?
AB  - Inflammation of the distal lung, which consists of the small airways (internal
      diameter <2 mm) and alveolar tissue, is an important feature of the asthma
      clinical syndrome comprising airway inflammation, airway hyperresponsiveness and
      bronchodilator-responsive expiratory airflow limitation. Support for this
      assertion is derived from histologic studies which have demonstrated evidence of
      inflammation in this anatomic compartment, along with additional studies, which
      have elucidated the radiologic and physiologic correlates of distal lung
      inflammation. Delivering inhaled drugs to this area is challenging and is
      dependent on a number of drug- and delivery device-related factors, as well as on
      a patient's inhaler technique and bronchial anatomy. Newer chlorofluorocarbon
      free formulations of inhaled corticosteroids such as hydrofluoroalkane propelled
      metered-dose inhalers and dry powder inhalers appear to have certain advantages
      with regard to drug delivery that facilitate improved drug delivery to the distal
      lung. Mounting evidence indicates that recognition and treatment of distal lung
      inflammation may be key components of appropriate asthma pharmacotherapy.

PMID- 16086597
TI  - Short-course antimicrobial therapy for community-acquired pneumonia.
AB  - Management of community-acquired pneumonia (CAP) remains surprisingly
      controversial. Optimal duration of antimicrobial therapy reflects one of the open
      questions due to the lack of sufficient randomized clinical trial data. Recently,
      there have been efforts to rationalize antimicrobial therapy of this disease.
      Trials addressing the issue of short-course antimicrobial therapy for CAP have
      revealed no adverse outcomes with a treatment duration of 5 days when compared
      with conventional courses of 7-10 days. There is accumulating evidence that a
      shorter duration of antimicrobial therapy may have benefits in patients with CAP,
      as it might enhance compliance, decrease the development of antimicrobial
      resistance, decrease the incidence and shorten the duration of adverse drug
      effects, reduce treatment costs and improve patient satisfaction with therapy.
      Nevertheless, remaining questions regarding the influence of patient selection,
      disease severity or choice of antimicrobial for short-course therapy indicate the
      need for further randomized controlled clinical trials in this area of research.
      This article summarizes current evidence for short-course therapy in patients
      with CAP and draws conclusions for clinical practice.

PMID- 16086598
TI  - Airway biofilms: implications for pathogenesis and therapy of respiratory tract
      infections.
AB  - The differentiation of bacterial biofilms in the airway environment, the
      pathogenesis of airway biofilm, and possible therapeutic methods are discussed.
      Biofilm diseases that characteristically involve the respiratory system include
      cystic fibrosis (CF), diffuse panbronchiolitis (DPB), and bronchiectasia with
      Pseudomonas aeruginosa (P. aeruginosa) infection. There is evidence to suggest
      that almost all strains of P. aeruginosa have the genetic capacity to synthesize
      alginate, a main matrix of biofilms, when ecological conditions are unfavorable
      for their survival. The bacteria inside the mature biofilm show increased
      resistance to both antibacterials and phagocytic cells, express fewer virulence
      factors because of their stationary state of growth, and are less stimulatory to
      the mucosa because of the 'sandwich binding'. These factors facilitate both the
      colonization of bacteria and their extended survival even under unfavorable
      conditions. Since the biofilm limits colonization to a latent form, the clinical
      symptoms in this situation are unremarkable. However, the clinical progression of
      both CF and DPB proceeds in two characteristic directions. The first is an acute
      exacerbation caused by planktonic bacteria that have germinated from the biofilm.
      The second is a slow progression of disease that is induced by harmful immune
      reactions. The harmful reactions are mediated by alginate, which induces antigen
      antibody reactions around the airways, as well as formation of circulating immune
      complexes that are deposited on lung tissue. Furthermore, the highest titer of
      bacterial permeability increasing anti-neutrophil cytoplasmic autoantibodies (BPI
      ANCA) is observed in association with highly impaired pulmonary function in
      patients with CF and DPB, as well as in patients with a lengthy period of
      colonization with P. aeruginosa. BPI-ANCA subsequently makes chronic airway
      infection even more intractable. The long-term use of 14- or 15-ring membered
      macrolides results in a favorable clinical outcome for patients with DPB and in
      some patients with CF. In the last 10 years, an increasing number of studies have
      reported secondary actions of macrolides that include effects on both airway and
      phagocytic cells, as well as an anti-biofilm activity. The 14- or 15-ring
      membered macrolides inhibit: (i) the alginate production from P. aeruginosa; (ii)
      the antibody reaction to alginate, which leads to a decrease in the immune
      complex formation; and (iii) the activation of the autoinducer 3-O-C12-homoserine
      lactone and subsequent expression of lasI and rhlI in quorum sensing systems in
      P. aeruginosa. These anti-biofilm actions of macrolides may represent their basic
      mechanisms of action on airway biofilm disease.

PMID- 16086599
TI  - Anti-inflammatory medications for cystic fibrosis lung disease: selecting the
      most appropriate agent.
AB  - The lung disease of cystic fibrosis (CF) is characterized by a self-sustaining
      cycle of airway obstruction, infection, and inflammation. Therapies aimed at
      decreasing the inflammatory response represent a relatively new strategy for
      treatment. Attention has focused primarily upon the therapeutic potential of
      corticosteroids and NSAIDs. Although beneficial, the use of systemic
      corticosteroids is limited by their unacceptable adverse effects. It is unclear
      if inhaled corticosteroids are a viable alternative, although their use in CF has
      dramatically increased in recent years. High-dose ibuprofen has been shown to
      slow progression of CF lung disease, but its use has not been widely adopted
      despite a favorable risk-benefit profile. Thus, other anti-inflammatory
      approaches are under investigation. Since the inflammatory response can be
      triggered by many stimuli and since the pathways activated by these stimuli
      produce many mediators, there are a plethora of targets for anti-inflammatory
      therapeutics. Specific antibodies, receptor antagonists, and counter-regulatory
      cytokines, such as interleukin (IL)-10 and interferon-gamma, inhibit the pro
      inflammatory mediators responsible for the damaging inflammation in the CF
      airway, including tumor necrosis factor-alpha, IL-1beta and IL-8. Studies of
      molecules that modulate intracellular signaling cascades that lead to the
      production of inflammatory mediators, are underway in CF. For patients with
      established disease, recent and projected advances in therapies that are directed
      at neutrophil products, such as DNase, antioxidants, and protease inhibitors,
      hold great promise for limiting the consequences of the inflammatory response. To
      optimize anti-inflammatory therapy, it is necessary to understand the mechanism
      of action of these agents in the CF lung to determine which agents will be most
      beneficial, and to determine which therapies should be initiated at what age and
      stage of lung disease. Hope remains that correction of the abnormal CF
      transmembrane conductance regulator protein or gene replacement therapy will be
      curative. However, correction of the basic defect must also correct the
      dysregulated inflammatory response in order to be effective. Until those
      therapies aimed at repairing the basic defect are realized, limiting the effects
      of the inflammatory process will be important in slowing the decline in lung
      function and thus prolonging survival in patients with CF.

PMID- 16086600
TI  - The role of tiotropium bromide, a long-acting anticholinergic bronchodilator, in
      the management of COPD.
AB  - Bronchodilator therapy forms the mainstay of treatment for symptomatic patients
      with COPD. Long-acting bronchodilators, which maintain sustained airway patency
      over a 24-hour period, represent an advance in therapy. Tiotropium bromide is a
      new long-acting inhaled anticholinergic agent with superior pharmacodynamic
      properties compared with the short-acting anticholinergic, ipratropium bromide.
      Tiotropium bromide has been consistently shown to have a greater impact than
      ipratropium bromide on clinically important outcome measures such as health
      status. The mechanisms of clinical benefit with tiotropium bromide are
      multifactorial, but improved airway function, which enhances lung emptying and
      allows sustained deflation of over-inflated lungs, appears to explain
      improvements in dyspnea and exercise endurance in COPD. Inhaled tiotropium
      bromide therapy has also been associated with reduction in acute exacerbations of
      COPD as well as reduced hospitalizations. The safety profile of tiotropium
      bromide is impressive: dry mouth is the most common adverse event and rarely
      necessitates termination of the drug. No tachyphylaxis to tiotropium bromide has
      been demonstrated in clinical trials lasting up to 1 year. There is preliminary
      information that the combination of long-acting anticholinergics and long-acting
      beta2-adrenoceptor agonists provides additive physiological and clinical
      benefits. According to recent international guidelines, long-acting
      bronchodilators should be considered early in the management of symptomatic
      patients with COPD in order to achieve effective symptom alleviation and
      reduction in activity limitation. Tiotropium bromide, because of its once-daily
      administration and its established efficacy and tolerability profile, has emerged
      as an attractive therapeutic option for this condition.

PMID- 16086601
TI  - Efficacy and safety of an oral formulation of cetirizine and prolonged-release
      pseudoephedrine versus budesonide nasal spray in the management of nasal
      congestion in allergic rhinitis.
AB  - INTRODUCTION: The aim of this study was to compare the decongestant properties
      and tolerability of oral cetirizine and pseudoephedrine in a prolonged release
      form with those of nasal (aqueous spray) budesonide. METHODS: Thirty-six
      individuals experiencing allergic rhinitis to house dustmites (HDM) participated
      in a study according to a randomized, crossover, two-period, two-treatment design
      with at least a 2-week washout period between treatments. In each period of 4
      consecutive days, medications were taken twice daily. On day 1, immediately after
      the first intake of medication, individuals were exposed to HDM extract in the
      Vienna Challenge Chamber (VCC) for 5 hours. The primary efficacy parameter was
      nasal congestion, assessed by active anterior rhinomanometry and rating of nasal
      cavity photos. RESULTS: Rhinomanometry and nasal cavity photos both indicated
      that cetirizine/pseudoephedrine efficacy was statistically superior to budesonide
      in the management of nasal congestion during VCC sessions. The efficacy of
      cetirizine/pseudoephedrine was similar to that of budesonide from the end of day
      1 up to day 4 when individuals were exposed to their natural environment post
      exposure to the aeroallergens. This study confirms the efficacy of
      cetirizine/pseudoephedrine and budesonide in the management of nasal congestion
      associated with allergic rhinitis. Both medications were well-tolerated.
      Cetirizine/pseudoephedrine was more effective than budesonide during HDM
      exposure, whereas budesonide became as effective as cetirizine/pseudoephedrine
      several hours post exposure to the allergens.

PMID- 16086602
TI  - A preference evaluation study comparing the sensory attributes of mometasone
      furoate and fluticasone propionate nasal sprays by patients with allergic
      rhinitis.
AB  - OBJECTIVE: Data on intranasal corticosteroids suggest that individual product
      attributes may influence patient preference for therapy in allergic rhinitis. The
      study objective was to compare product sensory attributes and their impact upon
      patient preference for scent-free mometasone furoate nasal spray (MFNS) versus
      fluticasone propionate nasal spray (FPNS) in patients with symptomatic allergic
      rhinitis. METHODS: In a double-blind, crossover study, 100 patients were
      randomized to MFNS microg followed by FPNS 200 microg, or vice versa. Patients
      rated the study drugs by completing an individual product sensory attributes
      questionnaire at the end of each period of drug administration. An overall
      sensory preference questionnaire was completed following crossover. RESULTS: A
      significantly greater number of patients preferred MFNS to FPNS (p < 0.05). MFNS
      was superior for a number of individual sensory attributes based on mean patient
      ratings: significantly fewer patients perceived scent/odor (immediately and 2
      minutes after drug administration; p < 0.001), taste (immediately after drug
      administration; p = 0.002), and after-taste (2 minutes after drug administration;
      p = 0.007) with MFNS compared with FPNS. Similarly, product sensory attribute
      preference data demonstrated that twice the number of patients preferred MFNS to
      FPNS for scent/odor (p = 0.0005), immediate taste (p = 0.005), and after-taste (p
      = 0.005). Fifty-four percent of patients said they would choose a prescription
      for MFNS compared with 33% for FPNS (p = 0.03). In addition, 47% of patients
      would be more likely to comply (use daily as directed) with MFNS compared with
      25% with FPNS (p = 0.03). CONCLUSION: Several individual sensory attributes of
      MFNS were rated significantly superior to FPNS. Overall, based on the tested
      sensory attributes, patients preferred MFNS to FPNS therapy for the treatment of
      allergic rhinitis.

PMID- 16086603
TI  - The effect of gender on one-day-old infants' behavior and heart rate responses to
      music decibel level.
AB  - The purpose of this study was to examine gender differences among full term
      infants' responses to music played at a range of decibel levels. These responses
      were measured by physiological data (heart rate) and behavioral data (behavior
      state score). All subjects (N = 36) were healthy, 24-48 hours old, and had passed
      a hearing screening at the time of testing. Heart rate and behavior state were
      recorded as male (n = 18) and female (n = 18) subjects listened to alternating 3
      minute periods of silence and music for 21 minutes. The music--an excerpt of an
      instrumental lullaby--was presented via small speakers placed on either side of
      each subject's head and played at three different loudness levels: 55-60 dB, 65
      70 dB, and 75-80 dB. Heart rate was measured using a pulse oximeter with a Y
      sensor attached to each subject's great toe, and behavior state was measured
      using a scale adapted from the Neonatal Behavioral Assessment Scale (Brazelton &
      Nugent, 1995). A two-way analysis of variance with repeated measures computed for
      both order and gender found no significant difference in heart rate or behavior
      state during the three loudness levels. Possible reasons for this lack of
      difference include enjoyment of the music regardless of intensity or physical
      inability to discriminate between the different levels.

PMID- 16086604
TI  - Cancer patients' interest and preferences for music therapy.
AB  - The reason for lack of routine integration of music therapy into healthcare may
      be that patients are not comfortable being involved in a music therapy
      intervention. Therefore, the goal of this study was to examine cancer patients'
      interest in and preferences for using 2 types of music therapy interventions,
      music-making and music listening. Sixty-five patients completed the Music
      Interest Survey in addition to standardized measures of coping, affect, anxiety,
      and fatigue. Results suggest adult cancer patients are interested in music
      therapy, especially music listening. Patient interest and preference were
      associated with negative affect, anxiety, age, perceived intervention-specific
      benefits, barriers, and self-efficacy. Findings highlight the need for a
      comprehensive assessment of patient needs and preferences prior to intervention.

PMID- 16086605
TI  - Preservice teachers' predictions, perceptions, and actual assessment of students
      with special needs in secondary general music.
AB  - The purpose of the current study was to examine preservice teachers' predictions
      and perceptions of students with special needs' level of mastery of specific
      music education concepts and actual grades achieved by these students using
      alternative assessments and testing accommodations within two subpopulations:
      students with emotional and/or behavior disorders, and students with acute
      cognitive delays. The preservice teachers predicted students within the EDBD
      class would achieve a significantly higher level of mastery of the music concepts
      than students within the ACD classroom. After the field experience, however, the
      preservice teachers perceptions of all students' level of mastery increased from
      predictions scores overall. Additionally, pre-service teachers were able to
      execute testing accommodations and implement successful alternative assessments
      which gave empirical data on the students' level of mastery of the music
      education concepts within the curriculum. Finally, there was no correlation
      between how the preservice teachers thought students would perform, how they
      thought the students performed, and how the students actually performed based on
      assessment data.

PMID- 16086606
TI  - Personality and music preferences: the influence of personality traits on
      preferences regarding musical elements.
AB  - The purpose of this scientific study was to determine how personality traits, as
      classified by Cattell, influence preferences regarding musical elements. The
      subject group consisted of 145 students, male and female, chosen at random from
      different Polish universities. For the purpose of determining their personality
      traits the participants completed the 16PF Questionnaire (Cattell, Saunders, &
      Stice, 1957; Russel & Karol, 1993), in its Polish adaptation by Choynowski
      (Nowakowska, 1970). The participants' musical preferences were determined by
      their completing a Questionnaire of Musical Preferences (specifically created for
      the purposes of this research), in which respondents indicated their favorite
      piece of music. Next, on the basis of the Questionnaire of Musical Preferences, a
      list of the works of music chosen by the participants was compiled. All pieces
      were collected on CDs and analyzed to separate out their basic musical elements.
      The statistical analysis shows that some personality traits: Liveliness (Factor
      F), Social Boldness (Factor H), Vigilance (Factor L), Openness to Change (Factor
      Q1), Extraversion (a general factor) have an influence on preferences regarding
      musical elements. Important in the subjects' musical preferences were found to be
      those musical elements having stimulative value and the ability to regulate the
      need for stimulation. These are: tempo, rhythm in relation to metrical basis,
      number of melodic themes, sound voluminosity, and meter.

PMID- 16086608
TI  - The temporal requirements for insulin signaling during development in Drosophila.
AB  - Recent studies have indicated that the insulin-signaling pathway controls body
      and organ size in Drosophila, and most metazoans, by signaling nutritional
      conditions to the growing organs. The temporal requirements for insulin signaling
      during development are, however, unknown. Using a temperature-sensitive insulin
      receptor (Inr) mutation in Drosophila, we show that the developmental
      requirements for Inr activity are organ specific and vary in time. Early in
      development, before larvae reach the "critical size" (the size at which they
      commit to metamorphosis and can complete development without further feeding),
      Inr activity influences total development time but not final body and organ size.
      After critical size, Inr activity no longer affects total development time but
      does influence final body and organ size. Final body size is affected by Inr
      activity from critical size until pupariation, whereas final organ size is
      sensitive to Inr activity from critical size until early pupal development. In
      addition, different organs show different sensitivities to changes in Inr
      activity for different periods of development, implicating the insulin pathway in
      the control of organ allometry. The reduction in Inr activity is accompanied by a
      two-fold increase in free-sugar levels, similar to the effect of reduced insulin
      signaling in mammals. Finally, we find that varying the magnitude of Inr activity
      has different effects on cell size and cell number in the fly wing, providing a
      potential linkage between the mode of action of insulin signaling and the
      distinct downstream controls of cell size and number. We present a model that
      incorporates the effects of the insulin-signaling pathway into the Drosophila
      life cycle. We hypothesize that the insulin-signaling pathway controls such
      diverse effects as total developmental time, total body size and organ size
      through its effects on the rate of cell growth, and proliferation in different
      organs.

PMID- 16086609
TI  - Antidepressant exposure may protect against decrement in frontal gray matter
      volumes in geriatric depression.
AB  - OBJECTIVES: Depressed elderly patients with and without antidepressant exposure
      were compared to normal controls to examine the effects of prior antidepressant
      exposure on regional brain gray matter volumes using magnetic resonance imaging
      (MRI). METHOD: The study was conducted from October 1999 to January 2003.
      Patients and controls were closely matched by age and education. They underwent
      comprehensive neuropsychiatric and physical examinations. Measures of the total
      frontal lobe and the frontal gray and white matter volumes corrected by the
      intracranial volume were obtained using MRI, together with clinical measures of
      medical burden. Historical information about prior exposure to antidepressant
      drugs was collected using multiple information sources. The groups were compared
      using multivariate analyses of covariance, controlling for age, sex, and medical
      burden. RESULTS: The study sample comprised 41 patients who met the DSM-IV
      criteria for major depressive disorder (32 women; 11 antidepressant exposure and
      30 drug-naive; mean age 70.5 years) and 41 controls (20 women; mean age 72.2
      years). In the multivariate analysis, the depressed group had smaller corrected
      orbitofrontal cortex (OFC) total and gray matter volumes compared to the controls
      (p < .01). However, depressed patients with prior antidepressant exposure had
      larger OFC gray matter volumes compared to drug-naive depressed patients, but
      smaller than those in normal controls (p = .005). This effect was not explained
      by the group differences in sex ratio, age at onset of depression, or the number
      or duration of depressive episodes. CONCLUSIONS: We observed larger OFC regional
      volumes in depressed patients exposed to antidepressants compared to the drug
      naive depressed subjects, but smaller than those in age-matched controls.
      Antidepressant exposure may protect against gray matter loss in geriatric
      depression.

PMID- 16086610
TI  - Clinical utility of magnetic resonance imaging radiographs for suspected organic
      syndromes in adult psychiatry.
AB  - OBJECTIVE: In psychiatric practice, adult patients are most commonly referred for
      magnetic resonance imaging (MRI) to screen for suspected organic medical diseases
      of the central nervous system that can mimic psychiatric syndromes. We identified
      the most common signs and symptoms prompting MRIs to establish the predictive
      value of these signs and symptoms for clinically pertinent organic syndromes.
      METHOD: This study was a retrospective chart review of psychiatric patients at
      the Veterans Affairs Greater Los Angeles Health Care Center (Los Angeles, Calif.)
      who were referred for MRI of the brain between 1996 and 2002. Patients referred
      for evaluation of dementia were excluded. The specific indications leading
      clinicians to obtain MRI were identified and grouped. In order to offset the
      uncertain significance of many MRI findings, for this study, the predictive value
      of each indication was calculated based on the percentage of patients in whom
      clinical management changed in response to MRI findings rather than on the
      percentage with any abnormal MRI results. RESULTS: Of 253 patients who had MRIs,
      38 (15%) incurred some degree of treatment modification as a result of MRI
      findings, including 6 patients in whom MRI identified a medical condition that
      became the focus of treatment. Six indications appeared most likely to prompt
      clinicians to obtain MRIs. Because pertinent results were associated with each of
      these indications, statistical evaluation did not reveal significant differences
      in their predictive values (chi(2) = 4.32, df = 5, p = .505). CONCLUSIONS: Unlike
      prior studies showing no value to screening radioimaging, this study shows MRI
      can be a useful screening test among patients suspected of having organic
      psychiatric disorders and that the common indications for MRI employed at one
      institution were predictive.

PMID- 16086611
TI  - Remission rates following antidepressant therapy with bupropion or selective
      serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized
      controlled trials.
AB  - BACKGROUND: Although it is widely believed that the various classes of
      antidepressants are equally effective, clinically meaningful differences may be
      obscured in individual studies because of a lack of statistical power. The
      present report describes a meta-analysis of original data from a complete set of
      studies comparing the norepinephrine/dopamine reuptake inhibitor (NDRI) bupropion
      with selective serotonin reuptake inhibitors (SSRIs; sertraline, fluoxetine, or
      paroxetine). METHOD: Individual patient data were pooled from a complete set of 7
      randomized, double-blind studies comparing bupropion (N = 732) with SSRIs
      (fluoxetine, N = 339; sertraline, N = 343; paroxetine, N = 49) in outpatients
      with major depressive disorder (DSM-III-R or DSM-IV); 4 studies included placebo
      (N = 512). Response and remission rates were compared at week 8 or endpoint in
      both the intent-to-treat sample, using the last-observation-carried-forward
      (LOCF) method to account for attrition, and the observed cases. Tolerability
      data, including incidence of sexual side effects, were also compared. RESULTS:
      The LOCF response and remission rates for the bupropion (62% and 47%) and SSRI
      (63% and 47%) groups were similar; both active therapies were superior to placebo
      (51% and 36%; all comparisons, p < .001). The same pattern of results was
      demonstrated on the observed cases analyses. Although bupropion and SSRIs were
      generally well tolerated, SSRI therapy resulted in significantly higher rates of
      sexual side effects as compared to both bupropion and placebo. SSRIs were also
      associated with more somnolence and diarrhea, and bupropion was associated with
      more dry mouth. CONCLUSION: Bupropion and the SSRIs were equivalently effective
      and, overall, both treatments were well tolerated. The principal difference
      between these treatments was that sexual dysfunction commonly complicated SSRI
      therapy, whereas treatment with bupropion caused no more sexual dysfunction than
      placebo.

PMID- 16086612
TI  - Association between pain and depression among older adults in Europe: results
      from the Aged in Home Care (AdHOC) project: a cross-sectional study.
AB  - OBJECTIVE: To assess the association between pain and depression in a population
      of older adults. METHOD: We conducted a cross-sectional study using data from the
      Aged in Home Care (AdHOC) database, which contains information on older adults
      receiving home care services in 11 European countries from 2001 to 2003. Pain was
      defined as any type of pain or discomfort manifested over the 7 days preceding
      the assessment. Depression was defined as a score >or= 3 on the Minimum Data Set
      Depression Rating Scale. RESULTS: Mean age of 3976 subjects entering the study
      was 82.3 years, and 2948 (74.1%) were women. Of the total sample, 2380 subjects
      presented with pain (59.9%), but its prevalence differed substantially among
      countries. Depression was diagnosed in 181 (11.3%) of the 1596 participants
      without pain and in 464 (19.5%) of the 2380 participants with pain (p < .001).
      After adjusting for potential confounders, pain was significantly associated with
      depression (odds ratio [OR] 1.76, 95% confidence interval [CI] = 1.43 to 2.17).
      This association seemed to be modified by sex. Compared to male participants
      without pain, women with pain were significantly more likely to present with
      depression (OR = 1.77; 95% CI = 1.29 to 2.42), while no significant difference
      was observed for women without pain (OR = 0.86; 95% CI = 0.61 to 1.22) and men
      with pain (OR = 1.24; 95% CI = 0.86 to 1.79). Among women, the association of
      pain and depression became progressively more pronounced as pain severity, pain
      frequency, and number of painful sites increased. CONCLUSION: This study
      documented that in a large sample of older adults living in the community, pain
      is associated with depression, especially among women.

PMID- 16086613
TI  - Improved sleep continuity and increased slow wave sleep and REM latency during
      ziprasidone treatment: a randomized, controlled, crossover trial of 12 healthy
      male subjects.
AB  - OBJECTIVE: Ziprasidone, an atypical antipsychotic, is a potent dopamine (D(2))
      and serotonin (5-HT(2A/C)) receptor blocker, has agonistic properties at the 5
      HT(1A) receptor, and blocks serotonin and norepinephrine reuptake. These
      transmitter systems are closely related to the regulation of sleep. METHOD: The
      aim of this double-blind, placebo-controlled, randomized, crossover study was to
      investigate the effects of ziprasidone on polysomnographic sleep structure and
      subjective sleep quality. Twelve healthy male subjects were randomly assigned to
      receive ziprasidone 40 mg or placebo for 2 sessions each composed of 2
      consecutive nights (night 1, standard sleep conditions; night 2, acoustic stress)
      5 days apart. Treatment was administered orally 2 hours before bedtime. The study
      was conducted from April 2004 to July 2004. RESULTS: Ziprasidone significantly
      increased total sleep time, sleep efficiency, percentage of sleep stage 2, and
      slow wave sleep; decreased the number of awakenings; and significantly affected
      tonic and phasic REM sleep parameters, i.e., it decreased percentage of REM and
      REM density and profoundly increased REM latency. CONCLUSION: Ziprasidone's
      effects on the sleep profile are somehow opposite to what is known about sleep of
      depressed patients (e.g., disturbances of sleep continuity, a reduciton of slow
      wave sleep, and a disinhibition of REM sleep). Its REM sleep-suppressing
      properties resemble those of most, although not all, antidepressants and may be
      clinically relevant. The drug also demonstrates sleep-consolidating properties
      under both standard routine and acoustic stress conditions. These effects are
      most likely related to ziprasidone's 5-HT(2C) antagonism, 5-HT(1A) agonism, and
      serotonin and norepinephrine reuptake inhibition.

PMID- 16086614
TI  - A trial of compliance therapy in outpatients with schizophrenia or
      schizoaffective disorder.
AB  - OBJECTIVE: To evaluate the efficacy of compliance therapy when delivered to
      outpatients with schizophrenia or schizoaffective disorder. METHOD: Thirty
      patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) were
      recruited from urban psychiatric outpatient clinics in an open trial of
      compliance therapy. Compliance therapy is a cognitive/psychoeducational approach
      consisting of 4 to 6 sessions lasting 30 to 60 minutes each. The primary outcome
      was electronically measured antipsychotic medication adherence. Adherence data
      were analyzed for effects during an initial treatment period (month -1 to month
      +1) and a subsequent 5-month follow-up period. Secondary outcome measures
      included clinician and patient ratings of adherence, symptoms, insight, and
      attitudes to medication treatment. Data were collected from August 2001 to
      January 2004. RESULTS: Compliance therapy was not associated with improvements in
      antipsychotic medication adherence. Patient ratings of adherence improved during
      the month -1 to month +1 period, but not in the subsequent 5-month follow-up. A
      diagnosis of schizoaffective disorder was associated with poorer adherence than
      was a diagnosis of schizophrenia during the month -1 to month +1 period. A higher
      degree of insight at baseline (end of month -1) was associated with greater
      adherence in the 5-month follow-up period. Symptoms, insight, and attitudes to
      medication treatment did not change significantly during the study. CONCLUSION:
      In this uncontrolled trial, outpatients with schizophrenia or schizoaffective
      disorder did not benefit from compliance therapy.

PMID- 16086615
TI  - Clinical and demographic features of atypical depression in outpatients with
      major depressive disorder: preliminary findings from STAR*D.
AB  - OBJECTIVE: To determine the frequency and demographic and clinical
      characteristics of depression with atypical features in a broadly representative
      sample of outpatients. METHOD: Data derived from the first 1500 patients with DSM
      IV major depressive disorder enrolled in the Sequenced Treatment Alternatives to
      Relieve Depression trial at 41 primary care and nonresearch psychiatric
      outpatient clinics. An algorithm based on the 30-item Inventory of Depressive
      Symptomatology-Clinician Rating (IDS-C30) determined presence or absence of
      depression with atypical features. Odds ratios determined whether a variety of
      demographic and clinical parameters differed between patients meeting and not
      meeting atypical criteria. RESULTS: Over 18% of the sample met criteria for
      atypical features based on items from the IDS-C30. The atypical group was more
      likely to be female and have an earlier age at onset, greater comorbidity with
      anxiety symptoms, and greater symptom severity compared with the nonatypical
      group. CONCLUSION: Previously identified features of atypical depression were
      confirmed in this large and broadly representative, nonresearch clinical
      population.

PMID- 16086616
TI  - Topiramate add-on in treatment-resistant schizophrenia: a randomized, double
      blind, placebo-controlled, crossover trial.
AB  - OBJECTIVE: We tested the hypothesis that topiramate is more effective than
      placebo in reducing symptoms in patients with treatment-resistant schizophrenia
      when combined with ongoing antipsychotic medication. METHOD: Twenty-six
      hospitalized treatment-resistant patients with chronic DSM-IV-diagnosed
      schizophrenia participated in a randomized, double-blind, placebo-controlled
      trial in which 300 mg/day of topiramate was gradually added to their ongoing
      treatment (clozapine, olanzapine, risperidone, or quetiapine) over two 12-week
      crossover treatment periods. Data were collected from April 2003 to November
      2003. RESULTS: In intention-to-treat analysis, topiramate was more effective than
      placebo in reducing Positive and Negative Syndrome Scale general psychopathologic
      symptoms (effect size = 0.7, p = .021), whereas no significant improvement was
      observed in positive or negative symptoms. CONCLUSION: Glutamate antagonist
      topiramate may be an effective adjuvant treatment in reducing general
      psychopathologic symptoms in patients with schizophrenia resistant to treatment
      with second-generation antipsychotics.

PMID- 16086617
TI  - Symptomatic remission in patients with bipolar mania: results from a double
      blind, placebo-controlled trial of risperidone monotherapy.
AB  - BACKGROUND: The purpose of this analysis was to assess rates of symptomatic
      remission in patients with bipolar mania receiving risperidone in a double-blind,
      parallel-group, multicenter, placebo-controlled trial conducted in India. METHOD:
      Two hundred ninety-one adult patients who met DSM-IV criteria for bipolar I
      disorder manic or mixed episode were randomly assigned to flexible doses of
      risperidone (1-6 mg/day, N = 146) or placebo (N = 145) for up to 3 weeks. An
      entry Young Mania Rating Scale (YMRS) score of >or= 20 was required at trial
      screening and baseline. Remission was defined as achieving and maintaining a YMRS
      score <or= 8 for the remainder of the trial or until censor. Time to first onset
      of remission was assessed using Cox proportional hazards model. Presence or
      absence of remission was analyzed using logistic regression. Data were collected
      from March 2001 to December 2001. RESULTS: Of the 291 patients randomly assigned
      to treatment, 290 received at least 1 postbaseline assessment and were included
      in the analysis. The patients' mean YMRS score at baseline was 37.2 +/- 7.9.
      Remission was achieved by 42% of patients in the risperidone group and 13% of
      patients in the placebo group. After adjusting for psychosis, baseline YMRS
      score, sex, number of mood cycles in the previous year, and treatment, the odds
      of remission for patients receiving risperidone was 5.6 (95% CI = 3.0 to 10.4;
      chi(2) = 29.9, p < .0001). Similarly, the adjusted hazard of remission for the
      risperidone patients was 4.0 (95% CI = 2.3 to 6.8; chi(2) = 25.9, p < .0001).
      CONCLUSION: A significant proportion of acutely manic patients receiving
      risperidone monotherapy achieved symptomatic remission within 3 weeks.

PMID- 16086618
TI  - Response and relapse in patients with schizophrenia treated with olanzapine,
      risperidone, quetiapine, or haloperidol: 12-month follow-up of the
      Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study.
AB  - OBJECTIVE: The primary aim of this study was to compare the effectiveness of 12
      months' treatment with olanzapine, risperidone, quetiapine, or haloperidol in
      preventing relapse of schizophrenia. The study also examined other measures of
      clinical effectiveness and tolerability. METHOD: Outpatients with schizophrenia
      (ICD-10 or DSM-IV), who initiated or changed antipsychotic treatment, entered
      this 3-year, naturalistic, prospective, observational study between November 2000
      and December 2001. At baseline, subsets of patients were prescribed monotherapy
      with olanzapine (N = 3222), risperidone (N = 1116), quetiapine (N = 189), or
      haloperidol (N = 256). Patients remaining on monotherapy were assessed using the
      Clinical Global Impression-Schizophrenia scale. Relapse rate was determined from
      the responder subset. Treatment patterns, patient perception of treatment
      compliance, substance and alcohol intake patterns, and treatment tolerability
      were recorded. Results are based on 12-month treatment data. RESULTS: Compared to
      haloperidol-treated patients, olanzapine- and risperidone-treated patients had
      approximately 3 to 4 times higher odds of response at 12 months (p <or= .001) and
      6 times lower odds of relapse (p <or= .001 for olanzapine-treated patients).
      Among patients treated with atypical antipsychotics, olanzapine- and risperidone
      treated patients had lower odds of relapse (although the difference was not
      significant at p <or= .001) and significantly higher odds of response (p <or=
      .001) compared to quetiapine-treated patients. The tolerability profile generally
      favored the atypical antipsychotics over haloperidol. CONCLUSION: These interim
      results support the findings of randomized controlled trials and verify that in
      this naturalistic study, patients treated with olanzapine or risperidone
      monotherapy were less likely to experience relapse than patients who received
      haloperidol. The clinical effectiveness and tolerability profile varied
      significantly between the atypical antipsychotics.

PMID- 16086619
TI  - Posttraumatic stress disorder among Israeli ex-prisoners of war 18 and 30 years
      after release.
AB  - BACKGROUND: The psychological responses to captivity were measured in a sample of
      former prisoners of war (POWs) 18 and 30 years after release from captivity.
      METHOD: 209 Israeli veterans of the 1973 Yom Kippur War (103 ex-POWs and 106
      controls) who had taken part in a previous study conducted in 1991 participated
      in the current study conducted in 2003. The study assessed current rates of
      posttraumatic stress disorder (PTSD), changes in PTSD over time, and the
      contribution of captivity severity (objective and subjective), sociode-mographic
      variables, and psychological appraisal and coping with captivity to predicting
      PTSD using standardized self-report questionnaires. RESULTS: Twenty-three percent
      of the ex-POWs met PTSD criteria and were 10 times more likely than controls to
      experience deterioration in their psychological condition in the 12-year interval
      between the 2 assessments. Almost 20% of ex-POWs who did not meet PTSD criteria
      in 1991 met criteria in the current assessment, in comparison to almost 1% of the
      controls. Current PTSD was predicted by younger age at the time of captivity, by
      loss of emotional control and higher subjective appraisal of suffering in
      captivity, and by a greater number of PTSD symptoms in the 1991 assessment.
      CONCLUSION: It is important to follow up and offer treatment to former POWs.
      Special attention should be paid to those who lost emotional control in captivity
      and to those who felt that the conditions of their captivity were severe.

PMID- 16086620
TI  - An open study of triiodothyronine augmentation of selective serotonin reuptake
      inhibitors in treatment-resistant major depressive disorder.
AB  - OBJECTIVE: In an open trial, we investigated the efficacy of triiodothyronine
      (T(3)) adjuvant to selective serotonin reuptake inhibitors (SSRIs) in subjects
      with major depressive disorder (MDD) resistant to SSRI treatment. METHOD: Twenty
      subjects who met DSM-IV criteria for MDD (mean +/- SD age = 44.3 +/- 10.3 years;
      55% [N = 11] women) and had failed to respond to a course of treatment of at
      least 8 weeks with an SSRI antidepressant were enrolled in a 4-week open-label
      augmentation treatment with T(3) 50 microg/day. Atypical and melancholic sub
      types of MDD were diagnosed using Structured Clinical Interview for DSM-IV Axis I
      Disorders criteria. We administered the 17-item Hamilton Rating Scale for
      Depression (HAM-D-17) 4 times during the study (which was conducted between 2001
      and 2003). RESULTS: During T(3) augmentation, the severity of depression
      decreased from an initial mean +/- SD HAM-D-17 score of 20.5 +/- 3.6 to a final
      HAM-D-17 score of 14.0 +/- 7.1 (p < .001). Seven subjects (35.0%) were treatment
      responders (HAM-D-17 reduction >or= 50%), and 6 subjects (30.0%) achieved
      clinical remission (final HAM-D-17 <or= 7). The 5 subjects with atypical
      depression experienced significantly (p < .01) greater clinical improvement
      (final HAM-D-17 scores 6.6 +/- 1.8 vs. 16.4 +/- 4.5), and higher rates of
      treatment response (100% [5/5] vs. 13.3% [2/15]) and remission (80.0% [4/5] vs.
      13.3% [2/15]), compared to subjects with nonatypical MDD. The 8 subjects with
      melancholic MDD experienced significantly (p < .05) greater depression severity
      at the end of the study compared to nonmelancholic MDD subjects (final HAM-D-17
      scores = 18.3 +/- 6.6 vs. 11.1 +/- 6.1). CONCLUSION: Triiodothyronine
      augmentation of SSRIs may be a promising treatment strategy in SSRI-resistant
      MDD, particularly in subjects with the atypical MDD subtype.

PMID- 16086621
TI  - Predictors of remission after electroconvulsive therapy in unipolar major
      depression.
AB  - CONTEXT: Electroconvulsive therapy (ECT) is the most effective biological
      treatment for major depression. However, there is little agreement about
      clinically useful predictors of acute ECT outcomes. OBJECTIVE: To assess whether
      age, sex, burden of comorbid physical illness, age at onset, history of
      recurrence, episode duration, chronic depression or comorbid dysthymia,
      melancholic features, episode severity, and medication resistance are predictors
      of remission after an acute course of ECT. DESIGN: We performed an analysis using
      data gathered prospectively in 328 patients with unipolar major depression
      (according to Research Diagnostic Criteria) treated with ECT. The study was
      conducted from 1993 through 1999. Patients had a pretreatment score of 21 or
      higher on the 24-item Hamilton Rating Scale for Depression (HAM-D). Treatment
      history was assessed using the Antidepressant Treatment History Form. Remission
      was defined as a 24-item HAM-D score of 10 or less and a 60% or more relative
      reduction of the HAM-D score. RESULTS: On univariate logistic regression,
      statistically significant predictors of nonremission were chronic
      depression/dysthymia, medication resistance, longer episode duration, and younger
      age. On backward elimination logistic regression, only medication resistance (OR
      = 1.67, 95% CI = 1.05 to 2.67) and chronic depression/ dysthymia (OR = 1.84, 95%
      CI = 1.06 to 3.21) were statistically significant predictors of nonremission.
      CONCLUSIONS: In patients with major depression, lower rates of remission after
      acute ECT are associated with medication resistance and chronicity, but not with
      age or burden of physical illness.

PMID- 16086622
TI  - Mood alterations during interferon-alfa therapy in patients with chronic
      hepatitis C: evidence for an overlap between manic/hypomanic and depressive
      symptoms.
AB  - BACKGROUND: Psychiatric side effects are common during interferon-alfa (IFN-alfa)
      therapy and often responsible for early treatment discontinuation, thus limiting
      its therapeutic potential. Depression is considered the hallmark of these side
      effects. However, irritability, anger/hostility, and manic/hypomanic episodes
      have also been reported, suggesting that these symptoms are important features of
      IFN-alfa-induced neuropsychiatric side effects. OBJECTIVE: The aim of this
      prospective study was to use item-by-item analysis to thoroughly characterize
      neuropsychiatric symptoms occurring during early IFN-alfa therapy in a large
      cohort of patients with chronic hepatitis C. METHOD: Ninety-three previously IFN
      alfa-naive patients treated with pegylated IFN-alfa plus ribavirin for chronic
      hepatitis C were studied. Neuropsychiatric assessments were conducted before
      initiation and after weeks 4 and 12 of antiviral therapy. They included the Mini
      International Neuropsychiatric Interview, the 10-item Montgomery-Asberg
      Depression Rating Scale, the State-Trait Anxiety Inventory, and the Brief Fatigue
      Inventory. RESULTS: Psychiatric events occurred in 30 patients (32%). They
      consisted of mood disorders in all cases: mania in 3 cases (10%), irritable
      hypomania in 15 cases (50%), and depressive mixed states in 12 cases (40%).
      Neurovegetative symptoms appeared within 4 weeks in most patients. In patients
      who developed mood disorders, sadness and depressive thoughts were present but
      minimal in severity. In contrast, inner tension and anxiety symptoms increased
      significantly over time only in these patients. CONCLUSIONS: Our results suggest
      that IFN-alfa-induced mood disorders are common and consist of an overlap between
      depressive and manic symptoms rather than a mere depression. The impact of such
      findings on therapeutic management should be investigated.

PMID- 16086623
TI  - Behavioral treatment of obesity in patients taking antipsychotic medications.
AB  - OBJECTIVE: Antipsychotic medications are associated with weight gain and
      metabolic dysregulation, yet little is known about the management of obesity
      among individuals with severe and persistent mental illness. Thus we sought to
      evaluate the potential utility of a behavioral weight control program for this
      population. METHOD: Outpatients receiving psychiatric care at a university
      medical center who had a body mass index (BMI; weight in kg/[height in m](2))
      >or= 30 and were currently taking antipsychotic medication participated in a 12
      week group behavioral weight control program. A medical chart review was
      conducted for each participant's body weight over the 10 months prior to
      beginning the program. A multiple baseline design was used to determine the
      impact of the intervention on BMI through 12-month posttreatment follow-up. We
      also assessed self-reported eating behavior, physical activity, and health
      related quality of life. Data were collected from October 2000 to July 2003.
      RESULTS: Among 35 patients who began the program, 29 (83%) completed treatment,
      with mean (+/- SD) weight loss of 5.04 (+/- 7.52) pounds (p = .001) and
      improvements in eating, activity, and quality of life. At 3-month posttreatment
      follow-up (N = 27; 77%), total mean weight loss was 7.14 (+/- 11.47) pounds (p =
      .003). Results of a longitudinal model based on general estimating equations
      indicated that, relative to the pretreatment period, BMI decreased significantly
      during treatment and remained stable through 12-month posttreatment follow-up.
      CONCLUSION: Behavioral weight control is a promising approach to the treatment of
      obesity among outpatients taking antipsychotic medications, but longer and more
      robust interventions are needed.

PMID- 16086624
TI  - Symptom clusters as predictors of late response to antidepressant treatment.
AB  - OBJECTIVE: While there is some indication from studies in the acute phase of
      antidepressant treatment that there are differences in the timing of improvement
      in symptoms, relatively little work has explored the patterns of change for
      specific symptom clusters and the predictability of these changes to signal
      eventual response during the acute phase of treatment. This article investigates
      the use of clusters of symptoms on the 17-item Hamilton Rating Scale for
      Depression (HAM-D-17) to define the pattern of late response versus nonresponse
      to antidepressant medication. METHOD: Using principal component analysis, the HAM
      D-17 was divided into 4 symptom clusters (mood, sleep/psychic anxiety, appetite,
      and somatic anxiety/weight). Data for 996 patients with major depressive disorder
      (DSM-III-R criteria), who participated in a 12-week acute phase study with
      nefazodone, were subjected to a post hoc analysis of changes in symptom cluster
      scores. Patients were divided into 3 groups: early responders (< 4 weeks), late
      responders (4-12 weeks), and nonresponders (> 12 weeks) as defined by < 50%
      reduction in HAM-D-17 scores from baseline. The late-responder and nonresponder
      groups were subjected to the principal component analysis. Data were collected
      from October 1992 to November 1994. RESULTS: There were significant differences
      in the pattern of symptom change on the mood cluster (weeks 3-4) (p < .0001), the
      sleep/psychic anxiety cluster (weeks 3-4) (p < .003), and the somatic
      anxiety/weight cluster (weeks 3-4) (p < .01) for the late responders compared to
      the nonresponders. Using change scores, a discriminant function analysis
      correctly assigned 127 of the 182 late responders and 85 of the 133
      nonresponders, or 70% of the late responders and 64% of the nonresponders, to
      their final response groups. CONCLUSION: Monitoring changes in symptom clusters
      from the HAM-D-17 during this crucial early stage (first 4 weeks) can be used to
      distinguish late responders (after week 4) from nonresponders. Successful
      identification of nonresponders based on symptom cluster change in the first 4
      weeks would facilitate a shortening of an ineffective treatment trial and allow
      for necessary changes in treatment strategy, helping physicians more closely
      follow treatment guidelines.

PMID- 16086625
TI  - Increased risk of cerebrovascular adverse events and death in elderly demented
      patients treated with atypical antipsychotics: what's a clinician to do?

PMID- 16086626
TI  - Possible bipolar nature of irritability in major depressive disorder.

PMID- 16086627
TI  - Consensus development conference on antipsychotic drugs and obesity and diabetes:
      response to consensus statement.

PMID- 16086629
TI  - Antipsychotic-induced sexual dysfunction and the strength of the evidence.

PMID- 16086632
TI  - It looks like "bradyphylaxis" to me.

PMID- 16086634
TI  - Potential therapeutic role of peroxisome proliferator activated receptor-gamma
      agonists in psoriasis.
AB  - Psoriasis is a chronic inflammatory condition affecting 1 - 3% of the world's
      population. Despite the availability of several agents, therapeutic options
      remain limited. With a better understanding of the pathophysiology of psoriasis,
      several potential therapeutic targets have been identified. Peroxisome
      proliferator activated receptors have been shown to play a role in cutaneous
      homeostasis. This review focuses on the potential therapeutic role of peroxisome
      proliferator activated receptor-gamma agonists in psoriasis and the possibility
      for the future prospects.

PMID- 16086633
TI  - Niche-independent symmetrical self-renewal of a mammalian tissue stem cell.
AB  - Pluripotent mouse embryonic stem (ES) cells multiply in simple monoculture by
      symmetrical divisions. In vivo, however, stem cells are generally thought to
      depend on specialised cellular microenvironments and to undergo predominantly
      asymmetric divisions. Ex vivo expansion of pure populations of tissue stem cells
      has proven elusive. Neural progenitor cells are propagated in combination with
      differentiating progeny in floating clusters called neurospheres. The proportion
      of stem cells in neurospheres is low, however, and they cannot be directly
      observed or interrogated. Here we demonstrate that the complex neurosphere
      environment is dispensable for stem cell maintenance, and that the combination of
      fibroblast growth factor 2 (FGF-2) and epidermal growth factor (EGF) is
      sufficient for derivation and continuous expansion by symmetrical division of
      pure cultures of neural stem (NS) cells. NS cells were derived first from mouse
      ES cells. Neural lineage induction was followed by growth factor addition in
      basal culture media. In the presence of only EGF and FGF-2, resulting NS cells
      proliferate continuously, are diploid, and clonogenic. After prolonged expansion,
      they remain able to differentiate efficiently into neurons and astrocytes in
      vitro and upon transplantation into the adult brain. Colonies generated from
      single NS cells all produce neurons upon growth factor withdrawal. NS cells
      uniformly express morphological, cell biological, and molecular features of
      radial glia, developmental precursors of neurons and glia. Consistent with this
      profile, adherent NS cell lines can readily be established from foetal mouse
      brain. Similar NS cells can be generated from human ES cells and human foetal
      brain. The extrinsic factors EGF plus FGF-2 are sufficient to sustain pure
      symmetrical self-renewing divisions of NS cells. The resultant cultures
      constitute the first known example of tissue-specific stem cells that can be
      propagated without accompanying differentiation. These homogenous cultures will
      enable delineation of molecular mechanisms that define a tissue-specific stem
      cell and allow direct comparison with pluripotent ES cells.

PMID- 16086635
TI  - Personalised medicine for cancer: from drug development into clinical practice.
AB  - Personalised management of cancer means the prescription of specific therapeutics
      that are best suited for an individual patient and the type of tumour. Molecular
      diagnostics influences cancer management in several ways that aid
      personalisation. These technologies are enabling the classification of cancer,
      using molecular profiles, as a basis for more effective personalised therapies.
      Using microarrays, classification of a cancer based on the gene expression
      profile is important for personalising cancer therapy. Molecular imaging, such as
      by positron emission tomography, enables determination of tumour response to drug
      action at the molecular level. The combination of diagnostics with therapeutics-
      an important feature of personalised cancer therapy--is facilitated by the use of
      monoclonal antibodies and nanobiotechnology. Development of drug resistance--an
      important problem in cancer management--varies according to the anticancer agent,
      type of tumour and individual patient. There are no universal strategies to
      overcome drug resistance in cancer. Various efforts to deal with this problem
      should be tailored to each patient, and examples are given in this review. A
      better understanding of cancer biology will facilitate rational drug discovery
      for cancer, by linking the various pathways involved to targeted therapies.
      Oncoproteomics will play an important role in the development of personalised
      cancer therapy. Use of pharmacogenomic technologies in early clinical trials is
      enabling rapid assessment of the efficacy of anticancer agents, and reducing the
      time of drug development. Application of pharmacogenetics will reduce the adverse
      effect of anticancer drugs. Cell/gene therapies, cancer vaccines and RNA
      interference will facilitate the development of personalised cancer therapy.

PMID- 16086637
TI  - Advances in male hormone substitution therapy.
AB  - Increased awareness of the clinical diagnosis of male hypogonadism has resulted
      in the wider use of androgen substitution therapy. Clinical signs and symptoms
      together with a low serum testosterone level confirm the diagnosis of male
      hypogonadism. Androgen replacement results in improved sexual function, mood,
      muscle mass and bone density in most hypogonadal men. Such benefits must be
      assessed against potential risks. In older men, the potential risks of androgen
      treatment of hypogonadism are not known. Many delivery systems for androgen
      substitution are now available; the preparation chosen depends on the choice of
      the patient and his physician. Selective androgen receptor modulators offer
      tissue selective biological effects and the possibility of attaining maximum
      efficacy and minimum adverse effects.

PMID- 16086636
TI  - Neoadjuvant systemic therapy for breast cancer: an overview and review of recent
      clinical trials.
AB  - Neoadjuvant chemotherapy (NAC) is long established as part of the multi-modality
      management of locally advanced breast cancer or inflammatory breast cancer,
      leading to significantly improved outcome. Numerous recent studies have compared
      the use of anthracycline-based NAC with adjuvant chemotherapy in earlier-stage
      disease, and have shown equivalent disease-free and overall survival rates with
      increased breast conservation rates. These studies have also shown that a
      pathological complete response after NAC is associated with improved long-term
      outcome. More recently, the taxanes have been introduced into clinical trials of
      NAC with increased overall and pCR rates. However, there is no evidence that the
      addition of taxanes to neoadjuvant anthracycline-based chemotherapy significantly
      improves long-term disease free survival or overall survival. This paper reviews
      these trials, as well as trials of dose-dense and trastuzumab-containing NAC
      regimens. The review discusses the potential for NAC to replace prolonged
      adjuvant trials in the assessment of new therapeutic agents (using pathological
      complete response as a surrogate for long-term outcome), to be used as an in vivo
      chemosensitivity assay to guide further treatment, and to identify molecular
      markers that correlate with tumour sensitivity or resistance to chemotherapeutic
      agents so that the treatment of patients can be individualised.

PMID- 16086638
TI  - Reducing risk of cardiovascular events in noncardiac surgery.
AB  - Cardiac adverse events are a major cause of complications in noncardiac surgery.
      The benefit of preventive coronary artery revascularisation in stable patients
      before noncardiac surgery has recently been clarified: in the short-term there is
      no reduction in the number of postoperative myocardial infarction, deaths or
      hospital length of stay. Coronary artery revascularisation should be limited to
      these patients who have a well-defined need for the procedure, independent of the
      need of noncardiac surgery. Optimising medical therapy remains the best option
      for reducing perioperative complications in stable patients: the addition of
      statin therapy in candidates for noncardiac surgery with known or strongly
      suspected coronary disease may be conceived. There is compelling evidence for the
      use of beta-blockers in reducing cardiac risk. This review presents the studies
      that support the beneficial effect of beta-blockers, pharmacological effects and
      some practical aspects in noncardiac surgery. In the management of most of these
      patients, the use of beta-blockers can aid in the avoidance of a preoperative
      stress test. The remaining problem to solve is the cost-effective identification
      of the small group of patients in which the protective effect of beta-blocker
      therapy is insufficient and a cardiac revascularisation should be considered.

PMID- 16086639
TI  - Haemophilia B: Christmas disease.
AB  - Haemophilia B is an inherited bleeding disorder associated with a deficiency of
      coagulation factor IX. The hallmark of the severe phenotype is recurrent and
      spontaneous bleeding into joints, which can lead to joint deformity and arthritis
      at an early age. Recombinant factor IX is now increasingly regarded as the
      treatment of choice because it does not transmit human pathogens. All patients in
      the UK now receive this product exclusively. Conventional treatment now consists
      of the administration of recombinant factor IX concentrate on a prophylactic
      basis to prevent bleeds and, hence, minimise disability in the long term. Trials
      of gene therapy are also underway, but these are in the very early stages and
      will not be a realistic option for at least another 20 years.

PMID- 16086640
TI  - Short-term medical management of hydrocephalus.
AB  - Hydrocephalus is an excess accumulation of cerebrospinal fluid in or around the
      brain that can be produced by a broad spectrum of disorders. It can develop at
      any age and its incidence is increasing, both in infants and adults. Although the
      standard treatment of hydrocephalus is cerebrospinal fluid shunting, there are
      certain circumstances in which medical treatment, alone or in combination with
      shunting, has been suggested as an alternative. This review aims to present and
      discuss the indications for pharmacological treatment in the medical management
      of hydrocephalus, and the drugs most frequently used. Carbonic anhydrase
      inhibitors, loop diuretic agents, osmotic agents and fibrinolytic therapy are
      discussed. The most suitable drug seems to be acetazolamide, alone or in
      combination with furosemide. At present, osmotic agents are no longer used in the
      treatment of hydrocephalus. Fibrinolytic therapy administered directly into the
      ventricular system may not avoid the need for shunt placement, but may help in
      the management of hydrocephalus by preventing or reducing the rate of catheter
      obstruction and accelerating clot resolution.

PMID- 16086641
TI  - Treatment of focal segmental glomerulosclerosis.
AB  - Focal segmental glomerulosclerosis (FSGS) is not a disease, but a lesion
      affecting the podocyte. Secondary FSGS may be due to a host of various factors,
      and patients are rarely nephrotic, requiring symptomatic treatment only. The best
      prognostic feature of nephrotic FSGS is its response to corticosteroids. Some
      forms are most likely of immunological origin, relapse in a renal transplant and
      justify immunosuppressive treatment. In a growing number of cases, genetic
      profiling of molecules that contribute to the podocyte slit diaphragm
      permselectivity to albumin has identified defects that do not represent
      indications for immunosuppression. In the other forms, corticosteroids and
      cyclosporin A (CsA) remain the mainstay of treatment, with better efficacy when
      CsA is associated with steroids. The renal tolerability of CsA is reasonably good
      when the dosage is low. CsA dependency is not constant. Alkylating agents are
      reluctantly indicated in steroid-sensitive forms, which are rare. They are mostly
      ineffective in steroid-resistant forms. Tacrolimus seems a promising therapy with
      low toxicity, but it is usual for dependency on the drug to occur. Sirolimus
      seems to be ineffective. Azathioprine is not considered indicated, despite rare
      reports with favourable results, which would deserve further controlled trials.
      Recent publications indicate that mycophenolate mofetil might usefully find a
      place in the treatment. Plasmapheresis is of no avail outside the special case of
      relapse in a transplanted kidney. Immunoabsorption of the elusive substance that
      causes the nephrotic syndrome and its relapse on a transplant has not led to
      practical treatment options.

PMID- 16086642
TI  - Controlling sialorrhoea: a review of available treatment options.
AB  - Sialorrhoea (drooling or excessive salivation) is a common symptom of many
      neurological diseases (e.g., amyotropic lateral sclerosis, cerebral palsy and
      Parkinson's disease) and otolaryngologic diseases (tumours of upper aerodigestive
      tract). It is mostly caused by poor oral and facial muscle control in patients
      with swallowing dysfunction (secondary sialorrhoea). However, some cases of
      sialorrhoea are due to hypersecretion of saliva. These cases represent so-called
      primary sialorrhoea.

PMID- 16086643
TI  - Docetaxel/trastuzumab combination therapy for the treatment of breast cancer.
AB  - Trastuzumab is a humanised monoclonal antibody that targets the extra cellular
      domain of human epidermal growth factor receptor-2 (HER-2), which is
      overexpressed in approximately 20% of human breast cancers. Clinical benefit has
      been shown in breast cancer patients with HER-2 amplification or overexpression
      when trastuzumab is used alone or in combination with chemotherapy. Docetaxel is
      one of the most potent chemotherapy agents in the treatment of patients with
      metastatic and early-stage breast cancer. The rationale for combining these two
      drugs is based not only on preclinical synergic data, but also on expanding
      clinical results. This article reviews the results of trials investigating this
      two-drug combination, as well as the triple combinations including docetaxel and
      trastuzumab with platinum salts. These combinations appear to be amongst the most
      active therapies for the treatment of patients with HER-2-positive breast cancer
      in metastatic and potentially adjuvant settings.

PMID- 16086644
TI  - Review of atazanavir: a novel HIV protease inhibitor.
AB  - Atazanavir is a novel and potent protease inhibitor that differs from other
      protease inhibitors because of its good gastrointestinal tolerability, once-daily
      dosing, low pill burden and it does not seem to cause insulin resistance or lipid
      elevations in short-term use. Atazanavir produces an increase in indirect
      bilirubin levels, which is not related to hepatotoxicity. The incidence of
      atazanavir-related hyperbilirubinaemia does not seem to be increased in hepatitis
      B or C coinfection. I50L is atazanavir's signature mutation. It has been shown in
      previously treated patients that resistance is likely when three or more protease
      inhibitor resistance-related primary mutations are present.

PMID- 16086645
TI  - Lopinavir/ritonavir in the treatment of human immunodeficiency virus infection.
AB  - The importance of combination antiretroviral therapy in HIV-infection has been
      well established. However, many available agents suffer shortcomings that limit
      their clinical value, including adverse effects, difficult dosing requirements
      and rapid development of resistance. Lopinavir/ritonavir (Kaletra) is a member of
      the protease inhibitor class, specifically designed to address some of these
      deficits. The drug is a coformulation of lopinavir with low-dose ritonavir,
      exploiting a favourable drug-drug interaction between the two that yields
      sustained increases in plasma levels of lopinavir. In large-scale clinical
      trials, lopinavir/ritonavir has demonstrated superior therapeutic efficacy when
      compared with other protease inhibitors. It exerts potent antiviral activity in
      both treatment-naive and experienced patients with an acceptable incidence of
      adverse effects. De novo development of resistance has not been described in
      large clinical trials with patients naive to antiretroviral therapy.
      Lopinavir/ritonavir has recently been approved for once-daily dosing in
      antiretroviral-naive patients.

PMID- 16086646
TI  - An update of irbesartan and renin-angiotensin system blockade in diabetic
      nephropathy.
AB  - Type 2 diabetes is a chief cause of pathologies such as cardiovascular disease,
      nephropathy and retinopathy, and its prevalence is increasing worldwide.
      Development of renal disease can be slowed by tight glycaemic control and
      treatment of associated hypertension with angiotensin-converting enzyme
      inhibition, as The Diabetes Control and Complications Trial and the UK
      Prospective Diabetes Study have demonstrated. Recent clinical trials have
      supported the use of angiotensin II receptor antagonists in the treatment of
      diabetic nephropathy, resulting in the approval of new therapeutic indications in
      the US and Europe. The main goal of this review is to demonstrate how results
      from the Programme for Irbesartan Mortality and Morbidity Evaluation and other
      recent studies, based on the effects of renin-angiotensin system blockade, can be
      appropriate in clinical practice, thus displaying benefits of irbesartan therapy
      at any stage of renal disease in diabetics.

PMID- 16086647
TI  - Relating statin therapy to C-reactive protein levels.
AB  - Inflammation is pivotal in atherosclerosis, and C-reactive protein (CRP) is an
      inflammatory marker that predicts cardiovascular events. The Reversal of
      Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial compared the
      standard lowering of low-density lipoprotein (LDL)-cholesterol with pravastatin
      40 mg/day, with the intense lowering of LDL-cholesterol with atorvastatin 80
      mg/day on atheroma volume in patients with coronary artery disease, and showed
      that the atheroma progressed by 2.7% in the pravastatin group, and remained
      unchanged in the atorvastatin group. At 18 months follow-up, the CRP levels were
      reduced from a baseline level of 2.8 mg/l to 1.8 mg/l by atorvastatin, whereas
      pravastatin had little effect, and there was a good correlation between both the
      ultrasonographic progression of disease and the reduction in CRP levels. The
      Pravastatin or Atorvastatin Evaluation and Infection Therapy--Thrombolysis in
      Myocardial Infarction 22 (PROVE IT-TIMI 22) trial compared the long-term effects
      of the standard lowering of LDL-cholesterol with pravastatin, with the intense
      lowering of LDL-cholesterol with atorvastatin in patients with an acute coronary
      syndrome. The primary end point was the first of death, myocardial infarction,
      unstable angina requiring hospitalisation, revascularisation or stroke, and, at
      the end of 2 years, was greater in the pravastatin than the atorvastatin group
      (26.3 versus 22.4%, respectively). Patients with CRP levels of 2 mg/l had lower
      rates of recurrent myocardial infarction or death from coronary causes than
      patients with higher levels. Further analysis should be undertaken to assess
      cardiovascular risk at different levels of CRP, including assessing
      cardiovascular risk at different levels in men and women. Definitive results
      about the importance of lowering CRP levels are not likely to be obtained until
      the results of the Justification for Use of Statins in Primary Prevention, an
      Intervention Trial in Evaluating Rosuvastatin (JUPITER) study are published.

PMID- 16086650
TI  - Treatment of dyslipidaemia in HIV-infected persons.
AB  - Accumulating evidence suggests that HIV-infected individuals have an increased
      risk of cardiovascular events. This risk seems to be at least partially mediated
      by dyslipidaemia, which is related to the use of highly active antiretroviral
      therapy (HAART). As HIV-infected individuals live longer due to HAART, their
      cardiovascular risk will invariably increase. Because HAART is likely to be used
      indefinitely, HAART-related dyslipidaemia has emerged as a major cardiovascular
      concern. This article summarises the evaluation of dyslipidaemia and
      cardiovascular risk in HIV-infected individuals, the potential pathophysiological
      and genetic mechanisms involved in HAART-related dyslipidaemia and the current
      treatment approaches. In general, dyslipidaemia is evaluated and treated as in
      HIV-negative persons. The first step is cardiovascular risk assessment and the
      determination of target lipid levels. A healthier lifestyle and, in particular,
      smoking cessation should be promoted. Lowering levels of low-density lipoprotein
      cholesterol (or, in the setting of significant hypertriglyceridaemia, non-high
      density lipoprotein cholesterol) is the primary target of intervention. Switching
      HAART to a more lipid-favourable regimen should be considered if this does not
      jeopardise virological control. Many patients will need lipid-lowering drug
      therapy. Appropriate low-density lipoprotein cholesterol target levels may be
      more difficult to reach than in the HIV-negative population, and the potential
      for drug interactions when using lipid-lowering agents together with HAART needs
      to be considered. The identification of HAART strategies with no or minimal
      metabolic toxicity, and the identification of the safest and most efficacious
      lipid-lowering therapies for HIV-infected individuals with dyslipidaemia are
      important research goals.

PMID- 16086651
TI  - Neonatal candidiasis: prophylaxis and treatment.
AB  - The incidence of candidiasis has risen in neonatal intensive care units as
      advances in medical therapy have allowed for increased survival of extremely
      preterm neonates. The mortality of candidiasis has been reported to be 20% by
      several multi-centre studies. Definitive guidance for prophylaxis and treatment
      is hindered by lack of large, multi-centre, randomised controlled trials.
      Systemic prophylaxis is currently not recommended for any neonatal population,
      and amphotericin B deoxycholate continues to be used as first-line therapy for
      the treatment of invasive disease.

PMID- 16086652
TI  - Echinocandins: role in antifungal therapy, 2005.
AB  - Novel therapies to treat invasive fungal infections have revolutionised the care
      of patients with candidiasis, aspergillosis and other less common fungal
      infections. Physicians in the twenty first century have access to safer versions
      of conventional drugs (i.e., lipid amphotericin B products), extended-spectrum
      versions of established drugs (i.e., voriconazole), as well as a new class of
      antifungal agents; the echinocandins. The increased number of options in the
      antifungal armamentarium is well timed, as the incidence of both invasive
      candidiasis and invasive aspergillosis, and the financial burden associated with
      these infections, have increased significantly in the past several decades. The
      increasing incidence of fungal infections has risen in parallel with the increase
      in critically ill and immunocompromised patients. Candida is the fourth most
      common bloodstream isolate, approximately 50% of which are non-albicans species.
      Estimates suggest there to be 9.8 episodes of invasive candidiasis per 1000
      admissions to surgical intensive care units, with attributable mortality at 30%
      and cost per episode of US44,000 dollars. The burden of candidiasis is even
      higher in the paediatric population, with Candida being the second most common
      bloodstream infection. The increase in non-albicans candidiasis mandates the
      introduction of new antifungal agents capable of treating these often azole
      resistant isolates. In addition, there has been a rise in the incidence of
      invasive aspergillosis, the most common invasive mould infection following
      haematopoietic stem cell transplantation, with an estimated incidence of 10 -
      20%. The mortality associated with invasive aspergillosis has increased by 357%
      since 1980. Unfortunately, the overall survival rate among patients treated with
      amphotericin B, and even voriconazole, remains suboptimal, as evidenced by the
      failure of treatment in 47% of patients in the landmark voriconazole versus
      amphotericin B trial. Given the increasing incidence and suboptimal outcomes of
      these serious fungal infections, novel therapies represent an opportunity for
      significant advancement in clinical care. The current challenge is to discover
      the optimal place for the echinocandins in the treatment of invasive fungal
      infections.

PMID- 16086653
TI  - New agents for the prevention of opportunistic infections in haematopoietic stem
      cell transplant recipients.
AB  - Over the past three decades, autologous and allogeneic haematopoietic stem cell
      transplants (HSCTs) have become effective treatments for a variety of malignant
      and nonmalignant conditions. Patients who undergo HSCT receive high doses of
      chemotherapy and/or radiation that induce a prolonged period of profound
      immunodeficiency, placing them at high risk for infection from a panoply of
      opportunistic organisms. Although supportive treatment for these patients has
      markedly improved, 10-20% of allogeneic HSCT recipients will ultimately succumb
      to infection. Joint guidelines to prevent opportunistic infection were released
      in 2000 by the Centers for Disease Control, the Infectious Diseases Society of
      America, and the American Society of Blood and Marrow Transplantation; however,
      treatment decisions for these patients are often based on limited studies or
      depend on institution-specific transplant protocols and antibiotic resistance
      patterns. This paper will discuss new agents for preventing bacterial, fungal and
      viral infections in HSCT recipients.

PMID- 16086654
TI  - Update on antimicrobial agents: new indications of older agents.
AB  - The discovery of newly recognised pathogens and the emergence of antimicrobial
      resistance have led to the development of new antimicrobial agents or to new
      indications for older agents. The indications have continued to increase because
      of new discoveries on the older agents' antimicrobial and non-antimicrobial
      activities. Macrolides and tetracyclines have received attention for their non
      antimicrobial properties and potential use in chronic inflammatory disorders.
      Doxycycline, minocycline and trimethoprim-sulfamethoxazole regained interest for
      their activity against methicillin-resistant Staphylococcus aureus, whereas
      colistin has regained interest for its activity against multiple drug-resistant,
      Gram-negative pathogens (i.e., Pseudomonas aeruginosa). Despite the recent
      development of new antimicrobial agents, older and less costly agents maintain an
      important role today in the treatment of infectious diseases.

PMID- 16086655
TI  - Combination therapy versus single agent chemotherapy in non-small cell lung
      cancer.
AB  - There is proven evidence of improved symptom control with platinum-based
      chemotherapy in the palliation of non-small cell lung cancer, and small but
      definite improvements in progression-free and overall survival when compared with
      best supportive care. The newer chemotherapy agents vinorelbine, gemcitabine,
      docetaxel and paclitaxel all have single agent activity, and in combination with
      cisplatin these provide superior quality of life and/or survival compared with
      the single agents, albeit with some increase in haematological toxicity. Doublet
      chemotherapy consisting of a new agent combined with platinum, cisplatin by
      preference where tolerated, has become the standard of care for advanced disease.
      The use of a functional assessment of fitness, rather than chronological age
      alone, is appropriate in the treatment of elderly patients. Although in this
      group there is evidence that doublets are superior to single agents, treatment
      should be undertaken with caution. In the second line setting where patients are
      unlikely to tolerate combination therapy, single agents have proven superiority
      over best supportive care. Patients with poor performance status (PS2) without
      comorbidity may tolerate combination therapy, but currently available evidence is
      insufficient to allow a definitive recommendation for combination or single-agent
      chemotherapy.

PMID- 16086656
TI  - Angiogenesis inhibitors in the treatment of cancer.
AB  - The field of cancer research has seen a marked shift in the past decade towards
      the exploration and development of non-conventional antitumour agents. One of the
      most widely studied approaches to therapy during this period has been that of
      antiangiogenesis. The published clinical trials and subsequent FDA approval (in
      February 2004) of the anti-vascular endothelial growth factor (VEGF) monoclonal
      antibody bevacizumab (Avastin, Genentech) for the treatment of colorectal cancer
      marked a milestone for antiangiogenesis therapy. Currently, preclinical and
      clinical research involving therapeutic targeting of VEGF and other mediators of
      angiogenesis continues in multiple tumour types. In addition to colorectal
      cancer, angiogenesis inhibitors are being investigated in the treatment of renal
      cell carcinoma, head and neck carcinoma, lung cancer, breast cancer, prostate
      cancer, and a variety of haematological malignancies. This article will discuss
      the background of antiangiogenesis research, preclinical and clinical data
      relating to the use of bevacizumab in the treatment of colorectal cancer, other
      completed clinical trials involving antiangiogenesis agents, and the potential
      future utility of these agents in the treatment of malignancy.

PMID- 16086657
TI  - Antiemetic therapy in cancer: an update.
AB  - Although nausea and vomiting are widely recognised as two of the most distressing
      symptoms of cytotoxic therapy, there is still concern over the adequate control
      of these symptoms in the cancer population. Recently updated Antiemetic Consensus
      Guidelines recommend the prophylactic treatment of all patients at moderate-to
      high risk of experiencing nausea and vomiting following chemotherapy and
      radiotherapy. It is important that these guidelines are fully adhered to;
      however, when considering which antiemetic regimen is most appropriate in an
      individual patient, it is also important to consider individual patient-related
      factors. In addition, certain patient groups, such as the young or the elderly,
      may be in need of specific consideration due to age-related factors that may
      influence treatment decisions.

PMID- 16086658
TI  - A review of acitretin, a systemic retinoid for the treatment of psoriasis.
AB  - Acitretin is a second-generation, systemic retinoid that has been approved for
      the treatment of psoriasis since 1997. It can be considered one of the treatments
      of choice for pustular and erythrodermic psoriasis. However, the efficacy of
      acitretin as a monotherapy for plaque psoriasis is less, although it is often
      used in combination therapy with other systemic psoriasis therapies, especially
      ultraviolet B or psoralen plus ultraviolet A phototherapy, to increase efficacy.
      Such combination treatments may potentially minimise toxicity by using lower
      doses of each of the two agents. All systemic retinoids are potent teratogens.
      The most common side effects are mucocutanous effects such as cheilitis and hair
      loss, which are dose-dependent. Acitretin is not immunosuppressive, is generally
      safe for long-term use and has no time limit restrictions, which makes it useful
      in combination therapy and for maintenance therapy.

PMID- 16086659
TI  - Clobetasol propionate foam in the treatment of psoriasis.
AB  - Psoriasis is a common, chronic, distressing skin disorder that frequently affects
      the scalp, skin, nails and joints. Despite treatment, many patients suffer from
      unremitting disease and decreased quality of life. Scalp-type psoriasis is
      particularly difficult to treat. Although topical corticosteroids are the
      mainstay of therapy for moderate-to-severe disease, patients frequently object to
      the messiness and unfavourable cosmetic appearance of topical treatments. In this
      context, foam vehicles, which have the advantage of minimal residue and increased
      ease of application, have emerged as novel alternatives to traditional creams,
      ointments and solutions. Clobetasol propionate foam 0.05% (OLUX, Connetics
      Corporation), a high potency topical steroid, has been shown to alleviate
      symptoms of several dermatological conditions, including scalp and body
      psoriasis, improve disease severity and increase quality of life. Dose should be
      limited to 50 g/week, given the risk of adrenal suppression. Because patient
      preference is an important determinant of medication efficacy in clinical
      practice, clobetasol foam is a useful new formulation in the treatment of
      psoriasis and other skin conditions.

PMID- 16086660
TI  - Somatropin for the treatment of short bowel syndrome in adults.
AB  - Somatropin (rDNA origin) injection (Zorbtive) is a highly purified preparation of
      human growth hormone (GH) produced from a mammalian cell line by recombinant DNA
      technology. It is the only human GH approved for the treatment of short bowel
      syndrome in patients receiving specialised nutritional support. The process of
      intestinal adaptation begins immediately after surgery and continues for 2-3
      years. During this period, the bowel begins to increase fluid and nutrient
      absorption. Under the influence of tropic factors, such as GH, intestinal
      adaptation is enhanced. Supplying a therapeutic regimen of GH, optimised diet and
      glutamine supplementation for 4 weeks to patients with short bowel syndrome who
      are dependent on parenteral nutrition, has been shown to reduce their long-term
      requirements for parenteral nutrition.

PMID- 16086661
TI  - Nebido: a long-acting injectable testosterone for the treatment of male
      hypogonadism.
AB  - Over the last six decades, tremendous strides have been made in the development
      of safe, efficacious and 'patient-friendly' modalities of testosterone
      replacement therapy in men. The most recent forms of androgen replacement that
      are in widespread use include testosterone patch and gel. These preparations are
      convenient in their use and deliver a physiological amount of testosterone.
      Although these transdermal preparations are gaining popularity, many hypogonadal
      men still receive treatment with intramuscular esters. Testosterone enanthate
      remains the most commonly prescribed ester. Although testosterone esters are
      efficacious in terms of improving bone and muscle mass, they possess unfavourable
      pharmacokinetics that result in fluctuations in the mood, energy and sexual
      function of patients. Furthermore, these esters need to be injected every 2-4
      weeks. Hence, there has been a need to develop long-acting esters that can be
      administered infrequently and deliver a physiological amount of testosterone
      without major fluctuations. Recently, injectable testosterone undecanoate
      (Nebido) has become available in Europe and will soon be marketed in south
      America, Asia and Australia. In this paper, the structure, pharmacokinetics,
      efficacy and side-effect profile of testosterone undecanoate will be reviewed and
      also compared with other existing testosterone esters.

PMID- 16086662
TI  - CLARITY about the use of clopidogrel in patients with acute coronary syndromes
      and myocardial infarction.
AB  - Clopidogrel was shown to have added benefits to aspirin in patients with acute
      coronary syndromes without ST-segment elevation in the Clopidogrel in Unstable
      Angina to Prevent Recurrent Events (CURE) trial. The cost in CURE was estimated
      to be US442 dollars greater in the clopidogrel group and the incremental cost
      effectiveness ratio (incremental cost/life-year gained) was US6318 dollars.
      Clopidogrel has also recently been shown to have added benefits to aspirin in
      patients with myocardial infarction with ST-segment elevation in the Clopidogrel
      as Adjunctive Reperfusion Therapy (CLARITY)--Thrombolysis in Myocardial
      Infarction (TIMI) 28 study. The primary efficacy composite end point in CLARITY
      was an occluded infarct-related artery, death from any cause prior to
      angiography, or recurrent myocardial infarction, and this end point occurred less
      in the clopidogrel group (15%, 262 of 1752 patients) than placebo group (21.7%,
      377 of 1739 patients). This difference was predominantly due to a reduction in
      the occluded infarct-related artery, which occurred in less of the clopidogrel
      (11.7%) than placebo group (18.4%). There was also a reduction in urgent
      revascularisations in the clopidogrel group of CLARITY. Thus, clopidogrel is
      effective and cost effective in acute coronary syndromes, and is also beneficial
      in patients with myocardial infarction with ST-segment elevation.

PMID- 16086663
TI  - 18th International Conference on Antiviral Research.
AB  - The 18th International Conference on Antiviral Research (ICAR) was held at the
      Princess Sofia Hotel in Barcelona, Spain, from 11th-14th April, 2005. This is a
      yearly international meeting sponsored by the International Society for Antiviral
      Research (ISAR). The current president of ISAR is John A Secrest 3rd of the
      Southern Research Institute. The scientific programme committee was chaired by
      John C Drach from the University of Michigan. ISAR was founded in 1987 to
      exchange prepublication basic, applied and clinical information on the
      development of antiviral, chemical and biological agents as well as to promote
      collaborative research. The ISAR has had a major role in the significant advances
      of the past decade in the reduction of the societal burdens of viral diseases by
      the focus of ICAR on the discovery and clinical application of antiviral agents.
      The 18th ICAR was organised as a series of focus presentations on specific viral
      groups consisting of oral and poster presentations of original research findings.
      In addition, the conference included plenary speakers, award presentations, a
      minisymposium on bioterrorism, and a satellite symposium on clinical antiviral
      drug developments. The size of the conference (> 50 oral and 250 poster
      presentations) necessitates limitation to the most noteworthy in the judgment of
      this reviewer. The current membership of the ISAR is approximately 700 with
      approximately 50% the membership in attendance.

PMID- 16086666
TI  - Distinct structure and activity recoveries reveal differences in metal binding
      between mammalian and Escherichia coli alkaline phosphatases.
AB  - The amino acids involved in the coordination of two Zn2+ ions and one Mg2+ ion in
      the active site are well conserved from EAP (Escherichia coli alkaline
      phosphatase) to BIAP (bovine intestinal alkaline phosphatase), whereas most of
      their surrounding residues are different. To verify the consequences of this
      heterology on their specific activities, we compared the activity and structure
      recoveries of the metal-free forms (apo) of EAP and of BIAP. In the present
      study, we found that although the sensitivities of EAP and BIAP to ions remained
      similar, significant differences in dimeric structure stability of apo-enzymes
      were observed between EAP and BIAP, as well as in the kinetics of their activity
      and secondary structure recoveries. After mild chelation inactive apo-EAP was
      monomeric under mild denaturing conditions, whereas inactive apo-BIAP remained
      dimeric, indicating that the monomer-monomer contact was stronger in the
      mammalian enzyme. Dimeric apo-EAP (0.45 microM, corresponding to 4 units/ml)
      recovered approx. 80% of its initial activity after 3 min incubation in an
      optimal recovery medium containing 5 microM Zn2+ and 5 mM Mg2+, whereas dimeric
      apo-BIAP (0.016 microM, corresponding to 4 units/ml) recovered 80% of its native
      activity after 6 h incubation in an optimal recovery medium containing 0.5 microM
      Zn2+ and 5 mM Mg2+. Small and different secondary structure changes were also
      observed during activity recoveries of apo-BIAP and apo-EAP, which were not in
      parallel with the activity recoveries, suggesting that distinct and subtle
      structural changes are required for their optimal activity recoveries.

PMID- 16086667
TI  - The kinetics of oxidation of GSH by protein radicals.
AB  - Current studies provide evidence that proteins are initial targets of ROS
      (reactive oxygen species) in biological systems and that the damaged proteins can
      in turn damage other cell constituents. This study was designed to test the
      possibility that protein radicals generated by ROS can oxidize GSH and assess the
      probability of this reaction in vivo by measurement of the rate constant of this
      reaction. Lysozyme radicals were generated by hydroxyl and azide radicals in
      steady-state gamma ray radiolysis. In the absence of dioxygen, a range of protein
      carbon-centred amino acid radicals were produced by the hydroxyl radicals, and
      defined tryptophan radicals by the azide radicals. In the presence of dioxygen,
      each carbon-centred radical was converted to a protein peroxyl radical. Each of
      the peroxyl radicals was able to oxidize a molecule of GSH, regardless of its
      location in the protein. The peroxyl radicals were 10 and 20 times more effective
      GSH oxidants than the carbon-centred radicals produced randomly in the lysozyme,
      or the defined tryptophan lysozyme radicals respectively. We obtained for the
      first time the rate constant of reaction between a protein free-radical and GSH.
      Lysozyme tryptophan carbon radicals generated by nanosecond pulse radiolysis and
      flash photolysis oxidized GSH with a rate constant of (1.05+/-0.05)x10(5) M(-1) x
      s(-1). Overall, the results are consistent with the hypothesis that protein
      radicals may be important intermediates in the pathway linking oxidative stress
      and damage in living organisms and emphasize the strongly enhancing role of
      dioxygen in this process.

PMID- 16086668
TI  - Polyclonal antibodies inhibit the glycation-induced inactivation of bovine Cu,Zn
      superoxide dismutase.
AB  - In vitro incubation of bovine Cu,Zn-SOD (Cu,Zn-superoxide dismutase) with
      glucose, ribose or fructose results in a remarkable inactivation of the enzyme.
      There was a progressive decrease in enzyme activity on incubation with glucose
      and, at the end of 7 days, only 26% of the initial activity remained. The
      inactivation was accompanied by a parallel decrease in the amount of protein
      detectable on gels after SDS/PAGE. Reaction of the sugars with SOD was
      ascertained using an immunoblot assay in which sugar-incubated SOD was
      derivatized with 2,4-dinitrophenylhydrazine and allowed to react with the
      dinitrophenol-specific antibody. Affinity purified antibodies from the sera of
      rabbits immunized with bovine SOD were highly effective in restricting the
      inactivation of the enzyme induced by glucose, ribose or fructose.

PMID- 16086669
TI  - The G0/G1 switch gene 2 is a novel PPAR target gene.
AB  - PPARs (peroxisome-proliferator-activated receptors) alpha, beta/delta and gamma
      are a group of transcription factors that are involved in numerous processes,
      including lipid metabolism and adipogenesis. By comparing liver mRNAs of wild
      type and PPARalpha-null mice using microarrays, a novel putative target gene of
      PPARalpha, G0S2 (G0/G1 switch gene 2), was identified. Hepatic expression of G0S2
      was up-regulated by fasting and by the PPARalpha agonist Wy14643 in a PPARalpha
      dependent manner. Surprisingly, the G0S2 mRNA level was highest in brown and
      white adipose tissue and was greatly up-regulated during mouse 3T3-L1 and human
      SGBS (Simpson-Golabi-Behmel syndrome) adipogenesis. Transactivation, gel shift
      and chromatin immunoprecipitation assays indicated that G0S2 is a direct
      PPARgamma and probable PPARalpha target gene with a functional PPRE (PPAR
      responsive element) in its promoter. Up-regulation of G0S2 mRNA seemed to be
      specific for adipogenesis, and was not observed during osteogenesis or
      myogenesis. In 3T3-L1 fibroblasts, expression of G0S2 was associated with growth
      arrest, which is required for 3T3-L1 adipogenesis. Together, these data indicate
      that G0S2 is a novel target gene of PPARs that may be involved in adipocyte
      differentiation.

PMID- 16086670
TI  - Human T-cell lymphotropic virus type I-transformed T-cells have a partial defect
      in ceramide synthesis in response to N-(4-hydroxyphenyl)retinamide.
AB  - Treatment with the synthetic retinoid HPR [N-(4-hydroxyphenyl)-retinamide] causes
      growth arrest and apoptosis in HTLV-I (human T-cell lymphotropic virus type-I)
      positive and HTLV-I-negative malignant T-cells. It was observed that HPR-mediated
      growth inhibition was associated with ceramide accumulation only in HTLV-I
      negative cells. The aim of the present study was to investigate the mechanism by
      which HPR differentially regulates ceramide metabolism in HTLV-I-negative and
      HTLV-I-positive malignant T-cells. Clinically achievable concentrations of HPR
      caused early dose-dependent increases in ceramide levels only in HTLV-I-negative
      cells and preceded HPR-induced growth suppression. HPR induced de novo synthesis
      of ceramide in HTLV-I-negative, but not in HTLV-I-positive, cells. Blocking
      ceramide glucosylation in HTLV-I-positive cells, which leads to accumulation of
      endogenous ceramide, rendered these cells more sensitive to HPR. Exogenous cell
      permeant ceramides that function partially by generating endogenous ceramide
      induced growth suppression in all tested malignant lymphocytes, were consistently
      found to be less effective in HTLV-I-positive cells confirming their defect in de
      novo ceramide synthesis. Owing to its multipotent activities, the HTLV-I-encoded
      Tax protein was suspected to inhibit ceramide synthesis. Tax-transfected Molt-4
      and HELA cells were less sensitive to HPR and C6-ceramide mediated growth
      inhibition respectively and produced lower levels of endogenous ceramide.
      Together, these results indicate that HTLV-I-positive cells are defective in de
      novo synthesis of ceramide and that therapeutic modalities that bypass this
      defect are more likely to be successful.

PMID- 16086672
TI  - Urgency: the key to defining the overactive bladder.

PMID- 16086671
TI  - Triosephosphate isomerase deficiency: consequences of an inherited mutation at
      mRNA, protein and metabolic levels.
AB  - Triosephosphate isomerase (TPI) deficiency is a unique glycolytic enzymopathy
      coupled with neurodegeneration. Two Hungarian compound heterozygote brothers
      inherited the same TPI mutations (F240L and E145Stop), but only the younger one
      suffers from neurodegeneration. In the present study, we determined the kinetic
      parameters of key glycolytic enzymes including the mutant TPI for rational
      modelling of erythrocyte glycolysis. We found that a low TPI activity in the
      mutant cells (lower than predicted from the protein level and specific activity
      of the purified recombinant enzyme) is coupled with an increase in the activities
      of glycolytic kinases. The modelling rendered it possible to establish the steady
      state flux of the glycolysis and metabolite concentrations, which was not
      possible experimentally due to the inactivation of the mutant TPI and other
      enzymes during the pre-steady state. Our results showed that the flux was 2.5
      fold higher and the concentration of DHAP (dihydroxyacetone phosphate) and
      fructose 1,6-bisphosphate increased 40- and 5-fold respectively in the
      erythrocytes of the patient compared with the control. Although the rapid
      equilibration of triosephosphates is not achieved, the energy state of the cells
      is not 'sick' due to the activation of key regulatory enzymes. In lymphocytes of
      the two brothers, the TPI activity was also lower (20%) than that of controls;
      however, the remaining activity was high enough to maintain the rapid
      equilibration of triosephosphates; consequently, no accumulation of DHAP occurs,
      as judged by our experimental and computational data. Interestingly, we found
      significant differences in the mRNA levels of the brothers for TPI and some
      other, apparently unrelated, proteins. One of them is the prolyl oligopeptidase,
      the activity decrease of which has been reported in well-characterized
      neurodegenerative diseases. We found that the peptidase activity of the affected
      brother was reduced by 30% compared with that of his neurologically intact
      brother.

PMID- 16086673
TI  - Epidemiology of nocturia.
AB  - The incidence of nocturia episodes increases with age and is associated with
      interrupted sleep and distress. There are no large differences in the incidence
      of nocturia between men and women, but young women tend to have it more
      frequently than young men, and very old men have it more often than very old
      women. The International Continence Society has defined nocturia as 'the number
      of voids recorded during a night's sleep: each void is preceded and followed by
      sleep.' This simple and useful definition should facilitate further
      epidemiological study of nocturia. Although there are many direct prevalence
      studies of nocturia, there is a great need for more advanced analytical
      epidemiological data on risk factors and comorbidity. Clinicians should question
      patients about nocturia and should consider this symptom in a broader sense than
      in its traditional association with benign prostatic obstruction in men and
      incontinence in women. There are several classic studies of nocturia. The nature
      of future epidemiological research will depend on the resolution of several
      methodological issues. Further evaluation of nocturia is warranted because of its
      high incidence among the general adult population.

PMID- 16086676
TI  - A developing view of the origins of urgency: the importance of animal models.
AB  - Although caution should be used when applying animal data to human physiology, if
      care is taken to differentiate between general principles and complications of
      detail, particular to the species being examined, then experimentation on animal
      models can reveal basic phenomena in the bladder that offer clues to the origin
      of urgency. Recent data from the whole isolated bladder of guinea pigs showed
      unexpected complexities in autonomous activity during the filling phase of the
      micturition cycle: small, transient increases in intravesical pressure were
      associated with propagating waves of contractile activity and localized stretches
      of bladder wall. This complex, coordinated activity suggests that there are
      mechanisms within the bladder wall devoted specifically to generating phasic
      activity. Thus, there appear to be two systems controlling detrusor contractions:
      one associated with overall contractions similar to the micturition contraction
      and the other generating phasic activity. The mechanisms generating the phasic
      activity appear to be the point of complex integration of both excitatory and
      inhibitory inputs. There is evidence that local activity in the bladder wall
      generates afferent discharge, which probably contributes to bladder sensations.
      Animal data suggest a novel motor/sensory system incorporating contractile
      (motor) events, which cause stretches resulting in activation of afferent nerves
      (sensory). The motor element of this system appears to be controlled in a highly
      complex fashion such that the amplitude and frequency of the motor activity can
      be modulated by a variety of inputs. This raises the possibility that the
      sensitivity of the system informing the central nervous system, and thus
      awareness of the bladder's state during the micturition cycle, can be
      manipulated, possibly via novel drugs targeted at areas involved in overactive
      bladder, including urgency incontinence.

PMID- 16086677
TI  - Objective measurement of bladder sensation: use of a new patient-activated device
      and response to neuromodulation.
AB  - Detrusor overactivity is the primary objective focus of most investigations into
      the diagnosis and management of patients with urgency incontinence. Patients with
      an overactive bladder are characteristically troubled by subjective sensations of
      bladder fullness and urinary urgency, and frequently void at low bladder volumes
      attained before noticeable detrusor overactivity occurs. Bladder sensations are
      therefore crucial to understanding voiding patterns and symptoms, but little
      progress has been made in objectively describing the range of these sensations,
      and adequate information is lacking about their response to neuromodulation.
      Towards this end, a keypad 'urge score' device was designed to measure sensations
      during bladder filling. This patient-activated device gathers information about
      patient perceptions of bladder filling and the successive stages of increasing
      bladder sensation, without prompting or intervention by the investigator. The
      accuracy of the 'urge keypad' during filling cystometrography was validated in
      patients with urgency incontinence, and compared with data abstracted from
      patient voiding diaries. The device provides reliable and repeatable measures of
      different bladder sensations, with excellent, statistically significant
      consistency between bladder volumes and corresponding levels of sensation.
      Subsequently, it was shown that the sensation of urgency can be suppressed by
      neuromodulation in most patients tested; this suppression occurs with
      improvements in bladder capacity and voided volumes. It is therefore suggested
      that urodynamics with concurrent sensory evaluation may offer a more useful
      assessment tool for selecting those patients for therapies such as
      neuromodulation who present predominantly with the symptom of urgency.

PMID- 16086679
TI  - Health-related consequences of overactive bladder: an economic perspective.
AB  - About 34 million people in the USA have an overactive bladder (OAB), a condition
      characterized by urinary urgency, with or without urinary incontinence, and
      usually frequency and nocturia. This condition is associated with increased
      health risks (e.g. urinary tract infection, falls and fall-related injuries,
      including broken bones), as well as admission to nursing homes and prolonged
      hospital stays. The annual costs associated with OAB in the community setting are
      >9 billion dollars, including 2.9 billion dollars for diagnosis and treatment,
      1.5 billion dollars for routine care, 3.9 billion dollars for treatment of health
      related consequences, and 841 million dollars in lost productivity. These cost
      patterns raise the possibility that treating OAB at an early stage may both
      improve patient care and minimize overall use of healthcare resources. However,
      before a thorough economic analysis of OAB can be undertaken, more data are
      needed about the long-term costs and the pathogenesis of OAB-related conditions.

PMID- 16086681
TI  - Characterization of glial cell line-derived neurotrophic factor family receptor
      alpha-1 in peripheral nerve Schwann cells.
AB  - Glial cell line-derived neurotrophic factor (GDNF) family receptor alpha-1
      (GFRalpha-1) is a receptor component of GDNF that associates with and activates
      the tyrosine kinase receptor Ret. To further understand GDNF and its receptor
      system in the PNS, we first characterized the expression of GFRalpha-1 in bovine
      peripheral nerve in vivo. GFRalpha-1 immunoreactivity was localized adjacent to
      the outermost layer of myelin sheath, as well as in the endoneurium and axoplasm.
      In a fractionation study, GFRalpha-1 was recovered mostly in the soluble
      fraction, although a small amount was recovered in the membrane fraction. A
      substantial amount of GFRalpha-1 in the membrane fraction was extractable by
      detergent and alkaline conditions. To further clarify the expression of GFRalpha
      1 in Schwann cells, we examined cultured rat Schwann cells and the Schwannoma
      cell line RT4. Schwann cells expressed GFRalpha-1 in both the soluble/cytosolic
      and membrane fractions, and the membrane form of GFRalpha-1 was expressed at the
      outer surface of the Schwann cell plasma membrane. We also confirmed the
      secretion of the soluble form of GFRalpha-1 from Schwannoma cells in a metabolic
      labeling experiment. These data contribute to our knowledge of the production,
      expression and functions of GFRalpha-1 in the PNS.

PMID- 16086682
TI  - APP substitutions V715F and L720P alter PS1 conformation and differentially
      affect Abeta and AICD generation.
AB  - The 37-43 amino acid Abeta peptide is the principal component of beta-amyloid
      deposits in Alzheimer's disease (AD) brain, and is derived by serial proteolysis
      of the amyloid precursor protein (APP) by beta- and gamma-secretase. gamma
      Secretase also cleaves APP at Val50 in the Abeta numbering (epsilon cleavage),
      resulting in the release of a fragment called APP intracellular domain (AICD).
      The aim of this study was to determine whether amino acid substitutions in the
      APP transmembrane domain differentially affect Abeta and AICD generation. We
      found that the APPV715F substitution, which has been previously shown to
      dramatically decrease Abeta40 and Abeta42 while increasing Abeta38 levels, does
      not affect in vitro generation of AICD. Furthermore, we found that the APPL720P
      substitution, which has been previously shown to prevent in vitro generation of
      AICD, completely prevents Abeta generation. Using a fluorescence resonance energy
      transfer (FRET) method, we next found that both the APPV715F and APPL720P
      substitutions significantly increase the distance between the N- and C-terminus
      of presenilin 1 (PS1), which has been proposed to contain the catalytic site of
      gamma-secretase. In conclusion, both APPV715F and APPL720P change PS1
      conformation with differential effects on Abeta and AICD production.

PMID- 16086683
TI  - Modulation of the cannabinoid CB2 receptor in microglial cells in response to
      inflammatory stimuli.
AB  - The cannabinoid system is known to be important in neuronal regulation, but is
      also capable of modulating immune function. Although the CNS resident microglial
      cells have been shown to express the CB2 subtype of cannabinoid receptor during
      non-immune-mediated pathological conditions, little is known about the expression
      of the cannabinoid system during immune-mediated CNS pathology. To examine this
      question, we measured CB2 receptor mRNA expression in the CNS of mice with
      experimental autoimmune encephalomyelitis (EAE) and, by real-time PCR, found a
      100-fold increase in CB2 receptor mRNA expression during EAE onset. We next
      determined whether microglial cells specifically express the CB2 receptor during
      EAE, and found that activated microglial cells expressed 10-fold more CB2
      receptor than microglia in the resting state. To determine the signals required
      for the up-regulation of the CB2 receptor, we cultured microglial cells with
      combinations of gamma-interferon (IFN-gamma) and granulocyte) macrophage-colony
      stimulating factor (GM-CSF), which both promote microglial cell activation and
      are expressed in the CNS during EAE, and found that they synergized, resulting in
      an eight to 10-fold increase in the CB2 receptor. We found no difference in the
      amount of the CB2 receptor ligand, 2-arachidonylglycerol (2-AG), in the spinal
      cord during EAE. These data demonstrate that microglial cell activation is
      accompanied by CB2 receptor up-regulation, suggesting that this receptor plays an
      important role in microglial cell function in the CNS during autoimmune-induced
      inflammation.

PMID- 16086684
TI  - Methamphetamine-induced inhibition of mitochondrial complex II: roles of
      glutamate and peroxynitrite.
AB  - High-dose methamphetamine (METH) is associated with long-term deficits in
      dopaminergic systems. Although the mechanism(s) which contributes to these
      deficits is not known, glutamate and peroxynitrite are likely to play a role.
      These factors are hypothesized to inhibit mitochondrial function, increasing the
      free radical burden and decreasing neuronal energy supplies. Previous studies
      suggest a role for the mitochondrial electron transport chain (ETC) in mediating
      toxicity of METH. The purpose of the present studies was to determine whether
      METH administration selectively inhibits complex II of the ETC in rats. High-dose
      METH administration (10 mg/kg every 2 h x 4) rapidly (within 1 h) decreased
      complex II (succinate dehydrogenase) activity by approximately 20-30%. In
      addition, decreased activity of complex II-III, but not complex I-III, of the
      mitochondrial ETC was also observed 24 h after METH. This inhibition was not due
      to direct inhibition by METH or METH-induced hyperthermia and was specific to
      striatal brain regions. METH-induced decreases in complex II-III were prevented
      by MK-801 and the peroxynitrite scavenger 5,10,15,20-tetrakis (2,4,6-trimethyl
      3,5-sulphonatophenyl) porphinato iron III. These findings provide the first
      evidence that METH administration, via glutamate receptor activation and
      peroxynitrite formation, selectively alters a specific site of the ETC.

PMID- 16086686
TI  - Mass spectrometric analysis reveals changes in phospholipid, neutral sphingolipid
      and sulfatide molecular species in progressive epilepsy with mental retardation,
      EPMR, brain: a case study.
AB  - Progressive epilepsy with mental retardation, EPMR, belongs to a group of
      inherited neurodegenerative disorders, the neuronal ceroid lipofuscinoses. The
      CLN8 gene that underlies EPMR encodes a novel transmembrane protein that
      localizes to the endoplasmic reticulum (ER) and ER-Golgi intermediate
      compartment. Recently, CLN8 was linked to a large eukaryotic protein family of
      TLC (TRAM, Lag1, CLN8) domain homologues with postulated functions in lipid
      synthesis, transport or sensing. By using liquid chromatography/mass spectrometry
      we analysed molecular species of major phosholipid and simple sphingolipid
      classes from cerebral samples of two EPMR patients representing a progressive and
      advanced state of the disease. The progressive state brain showed reduced levels
      of ceramide, galactosyl- and lactosylceramide and sulfatide as well as a decrease
      in long fatty acyl chain containing molecular species within these classes. Among
      glycerophospholipid classes, an increase in species containing polyunsaturated
      acyl chains was detected especially in phosphatidylserines and
      phosphatidylethanolamines. By contrast, saturated and monounsaturated species
      were overrepresented among phosphatidylserine, phosphatidylethanolamine and
      phosphatidylinositol classes in the advanced state sample. The observed changes
      in brain sphingo- and phospholipid molecular profiles may result in altered
      membrane stability, lipid peroxidation, vesicular trafficking or
      neurotransmission and thus may contribute to the progression of the molecular
      pathogenesis of EPMR.

PMID- 16086687
TI  - Leptin induces a novel form of NMDA receptor-dependent long-term depression.
AB  - It is becoming apparent that the hormone leptin plays an important role in
      modulating hippocampal function. Indeed, leptin enhances NMDA receptor activation
      and promotes hippocampal long-term potentiation (LTP). Furthermore, obese rodents
      with dysfunctional leptin receptors display impairments in hippocampal synaptic
      plasticity. Here we demonstrate that under conditions of enhanced excitability
      (evoked in Mg2+-free medium or following blockade of GABA(A) receptors), leptin
      induces a novel form of long-term depression (LTD) in area CA1 of the
      hippocampus. Leptin-induced LTD was markedly attenuated in the presence of D-(-)
      2-Amino-5-Phosphonopentanoic acid (D-AP5), suggesting that it is dependent on the
      synaptic activation of NMDA receptors. In addition, low-frequency stimulus-evoked
      LTD occluded the effects of leptin. In contrast, metabotropic glutamate receptors
      (mGluRs) did not contribute to leptin-induced LTD as mGluR antagonists failed to
      either prevent or reverse this process. The signalling mechanisms underlying
      leptin-induced LTD were independent of the Ras-Raf-mitogen-activated protein
      kinase signalling pathway, but were markedly enhanced following inhibition of
      either phosphoinositide 3-kinase or protein phosphatases 1 and 2A. These data
      indicate that under conditions of enhanced excitability, leptin induces a novel
      form of homosynaptic LTD, which further underscores the proposed key role for
      this hormone in modulating NMDA receptor-dependent hippocampal synaptic
      plasticity.

PMID- 16086688
TI  - Identification, expression and functional characterization of the GRAL gene.
AB  - The glial cell line-derived neurotrophic factor (GDNF) family is a group of
      neurotrophic factors with diverse biological functions. Members of the GDNF
      family exert their functions by interacting with a specific GDNF family receptor
      alpha (GFRalpha) and activation of the cRET. Here we report the identification
      and characterization of GDNF receptor-alpha-like (GRAL) gene. Sequence analysis
      indicated that GRAL is a distant homolog of the GFRalpha family, with 30% of its
      amino acid sequence identical to that of GFRalpha-3. There are two splice
      variants of GRAL: the full-length form (GRAL-A) represented by a 2080 bp mRNA and
      a short form (GRAL-B) represented by a 1833 bp mRNA. In adult mouse, GRAL
      transcripts have been found primarily in the CNS. In the developing mouse brain,
      the mRNA level of GRAL in the cerebrocortex and hippocampus reached a maximum at
      birth and declined afterwards. GRAL-A protein was localized predominantly in the
      plasma membrane. Overexpression of GRAL-A protected PC12 cells and cultured
      hippocampal neurons from serum starvation-induced cell apoptosis. The
      neuroprotective effect of GRAL was associated with marked inhibition of the Jun-N
      terminal kinase signaling pathway. Our results suggest that GRAL belongs to a
      superfamily of GFRalpha and might take part in neuroprotection and brain
      development.

PMID- 16086689
TI  - Astrocytes as antigen-presenting cells: expression of IL-12/IL-23.
AB  - Interleukin-12 (IL-12, p70) a heterodimeric cytokine of p40 and p35 subunits,
      important for Th1-type immune responses, has been attributed a prominent role in
      multiple sclerosis (MS) and its animal model, experimental autoimmune
      encephalomyelitis (EAE). Recently, the related heterodimeric cytokine, IL-23,
      composed of the same p40 subunit as IL-12 and a unique p19 subunit, was shown to
      be involved in Th1 responses and EAE. We investigated whether astrocytes and
      microglia, CNS cells with antigen-presenting cell (APC) function can present
      antigen to myelin basic protein (MBP)-reactive T cells, and whether this
      presentation is blocked with antibodies against IL-12/IL-23p40. Interferon (IFN)
      gamma-treated APC induced proliferation of MBP-reactive T cells. Anti-IL-12/IL
      23p40 antibodies blocked this proliferation. These results support and extend our
      previous observation that astrocytes and microglia produce IL-12/IL-23p40.
      Moreover, we show that stimulated astrocytes and microglia produce biologically
      active IL-12p70. Because IL-12 and IL-23 share p40, we wanted to determine
      whether astrocytes also express IL-12p35 and IL-23p19, as microglia were already
      shown to express them. Astrocytes expressed IL-12p35 mRNA constitutively, and IL
      23 p19 after stimulation. Thus, astrocytes, under inflammatory conditions,
      express all subunits of IL-12/IL-23. Their ability to present antigen to
      encephalitogenic T cells can be blocked by neutralizing anti-IL-12/IL-23p40
      antibodies.

PMID- 16086690
TI  - Regulation of expression of the novel IL-1 receptor family members in the mouse
      brain.
AB  - Members of the interleukin-1 (IL-1) family of cytokines are key mediators in the
      regulation of host defence responses and the development of inflammation in
      response to acute and chronic injury to the brain. Two major agonists, IL-1alpha
      and IL-1beta, bind to a membrane receptor complex composed of the type-1 IL-1
      receptor (IL-1RI) and the accessory protein (IL-1RAcP). The discovery of new
      orphan members of the IL-1 receptor superfamily (including ST2/T1, IL-1Rrp2,
      TIGIRR1 and -2, SIGGIR, IL-18Ralpha and IL-18Rbeta) has increased speculation
      that alternative IL-1 ligands signalling pathways exist in the brain. We
      demonstrate here that all the IL-1R-like orphan receptors are expressed by many
      brain cell types including astrocytes, microglia, oligodendrocytic progenitor
      cells and neurons. IL-18Rbeta expression was significantly increased in response
      to treatment of mixed glia with bacterial lipopolysaccharide (LPS) in vitro,
      whereas expression of IL-1Rrp2 and TIGIRR1 was reduced. Furthermore, IL-18Rbeta,
      IL-1Rrp2, but not TIGIRR1 expression, was increased in the brain in vivo in
      response to peripheral administration of LPS or middle cerebral artery occlusion
      (MCA). These results suggest possible roles for newly identified members of the
      IL-1 receptor family in CNS diseases.

PMID- 16086699
TI  - Progenitor cell injury after irradiation to the developing brain can be modulated
      by mild hypothermia or hyperthermia.
AB  - Ionizing radiation induced acute cell death in the dentate gyrus subgranular zone
      (SGZ) and the subventricular zone (SVZ). Hypomyelination was also observed. The
      effects of mild hypothermia and hyperthermia for 4 h after irradiation (IR) were
      studied in postnatal day 9 rats. One hemisphere was irradiated with a single dose
      of 8 Gy and animals were randomized to normothermia (rectal temperature 36
      degrees C for 4 h), hypothermia (32 degrees C for 4 h) or hyperthermia (39
      degrees C for 4 h). Cellular injury, e.g. chromatin condensation and
      nitrotyrosine formation, appeared to proceed faster when the body temperature was
      higher. Caspase-3 activation was more pronounced in the hyperthermia group and
      nuclear translocation of p53 was less pronounced in the hypothermia group 6 h
      after IR. In the SVZ the loss of nestin-positive progenitors was more pronounced
      (48%) and the size was smaller (45%) in the hyperthermia group 7 days post-IR.
      Myelination was not different after hypo- or hyperthermia. This is the first
      report to demonstrate that hypothermia may be beneficial and that hyperthermia
      may aggravate the adverse side-effects after radiation therapy to the developing
      brain.

PMID- 16086701
TI  - Glial cell line-derived neurotrophic factor-induced signaling in Schwann cells.
AB  - Glial cell line-derived neurotrophic factor (GDNF), a known survival factor for
      neurons, has recently been shown to stimulate the migration of Schwann cells
      (SCs) and to enhance myelination. GDNF exerts its biological effects by
      activating the Ret tyrosine kinase in the presence of
      glycosylphosphatidylinositol-linked receptor, GDNF family receptor (GFR) alpha1.
      In Ret-negative cells, the alternative transmembrane coreceptor is the 140-kDa
      isoform of neural cell adhesion molecule (NCAM) associated with a non-receptor
      tyrosine kinase Fyn. We confirmed that GDNF, GFRalpha1 and NCAM are expressed in
      neonatal rat SCs. We found that GDNF induces an increase in the partitioning of
      NCAM and heparan sulfate proteoglycan agrin into lipid rafts and that heparinase
      inhibits GDNF-signaling in SCs. In addition to activation of extracellular signal
      regulated kinases, and phosphorylation of cAMP response element binding protein,
      we found that cAMP-dependent protein kinase A and protein kinase C are involved
      in GDNF-mediated signaling in SCs. Although GDNF did not promote the
      differentiation of purified SCs into the myelinating phenotype, it enhanced
      myelination in neuron-SC cocultures. We conclude that GDNF utilizes NCAM
      signaling pathways to regulate SC function prior to myelination and at early
      stages of myelin formation.

PMID- 16086702
TI  - Impaired bolus transit across the esophagogastric junction in postfundoplication
      dysphagia.
AB  - OBJECTIVES: This study assessed the effect of fundoplication on liquid and solid
      bolus transit across the esophagogastric junction (EGJ) in relation to EGJ
      dynamics and dysphagia. METHODS: Twelve patients with gastro-esophageal reflux
      disease (GERD) were studied before and after fundoplication. Concurrent high
      resolution EGJ manometry and fluoroscopy were performed whilst swallowing liquid
      barium and a solid bolus. The EGJ transit time, EGJ opening duration, transit
      efficacy, and EGJ relaxation were measured. During the test symptoms of dysphagia
      were scored using a visual analog scale. RESULTS: The minimal opening aperture at
      fluoroscopy was located at the manometric EGJ in all subjects. Fundoplication
      markedly reduced the EGJ opening diameter from 1.0 +/- 0.1 to 0.6 +/- 0.1 cm (p <
      0.01) and rendered deglutative EGJ relaxation incomplete. After fundoplication, a
      higher intrabolus pressure was found (p < 0.05) associated with a reduced axial
      bolus length (p < 0.001). EGJ transit time increased from 6.9 +/- 0.9 to 9.8 +/-
      1.0 s for liquids (p < 0.01) and from 2.8 +/- 0.5 to 5.8 +/- 0.8 s (p < 0.01) for
      solids after fundoplication. No relation between EGJ transit and dysphagia scores
      was observed before fundoplication. In contrast, EGJ transit time significantly
      correlated with dysphagia scores both during liquid (r = 0.84; p < 0.01) and
      solid (r = 0.69; p < 0.05) bolus transit following fundoplication. CONCLUSIONS:
      Fundoplication patients exhibit a restricted hiatal opening and an incomplete
      deglutative EGJ relaxation. To facilitate EGJ transit despite these altered EGJ
      dynamics a higher intrabolus pressure is created by augmented bolus compression.
      Fundoplication increases EGJ transit time, the degree of which is associated with
      postoperative dysphagia.

PMID- 16086703
TI  - A nationwide study of mortality associated with hospital admission due to severe
      gastrointestinal events and those associated with nonsteroidal antiinflammatory
      drug use.
AB  - BACKGROUND: The worst outcome of gastrointestinal complications is death. Data
      regarding those associated with nonsteroidal antiinflammatory drug (NSAID) or
      aspirin use are scarce. AIM: To determine mortality associated with hospital
      admission due to major gastrointestinal (GI) events and NSAID/aspirin use.
      METHODS: The study was based on actual count of deaths from two different data
      sets from 2001. Study 1 was carried out in 26 general hospitals serving 7,901,198
      people. Study 2 used a database from 197 general hospitals, representative of the
      269 hospitals in the Spanish National Health System. Information regarding
      gastrointestinal complications and deaths was obtained throughout the Minimum
      Basic Data Set (CIE-9-MC) provided by participating hospitals. Deaths attributed
      to NSAID/aspirin use were estimated on the basis of prospectively collected data
      from hospitals of study 1. RESULTS: The incidence of hospital admission due to
      major GI events of the entire (upper and lower) gastrointestinal tract was 121.9
      events/100,000 persons/year, but those related to the upper GI tract were six
      times more frequent. Mortality rate was 5.57% (95% CI = 4.9-6.7), and 5.62% (95%
      CI = 4.8-6.8) in study 1 and study 2, respectively. Death rate attributed to
      NSAID/aspirin use was between 21.0 and 24.8 cases/million people, respectively,
      or 15.3 deaths/100,000 NSAID/aspirin users. Up to one-third of all NSAID/aspirin
      deaths can be attributed to low-dose aspirin use. CONCLUSION: Mortality rates
      associated with either major upper or lower GI events are similar but upper GI
      events were more frequent. Deaths attributed to NSAID/ASA use were high but
      previous reports may have provided an overestimate and one-third of them can be
      due to low-dose aspirin use.

PMID- 16086704
TI  - Seven versus ten days of rabeprazole triple therapy for Helicobacter pylori
      eradication: a multicenter randomized trial.
AB  - BACKGROUND: Ten-day triple therapy is somewhat more effective than 7-day
      treatment for curing Helicobacter pylori infection. Recent studies have suggested
      that rabeprazole-a proton pump inhibitor with fast onset of acid inhibition-could
      raise the efficacy of 7-day therapies to the levels obtained with 10-day
      treatment. OBJECTIVE: To compare the efficacy of 7- and 10-day rabeprazole-based
      triple therapy for H. pylori eradication. PATIENTS AND METHODS: Four hundred and
      fifty-eight patients were randomized to 7 or 10 days of triple therapy, including
      rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1 g, all twice a day.
      Cure rates were evaluated by urea breath test. RESULTS: Two hundred and thirty
      seven patients received 7-day and 221 received 10-day therapy. Groups were
      comparable in terms of demographic variables. Intention to treat cure rates were
      73.8% (95% CI: 67-79%) for 7-day and 79.6% (95%: CI:74-85%) for 10-day therapy
      (p= 0.09). Per-protocol cure rates were 81.8% (95% CI:76-86%) and 89.3% (95% CI:
      84-93%), p= 0.02, respectively. Cure rates were similar in peptic ulcer patients
      but in subjects without ulcer they were clearly lower for 7-day therapy:
      66%versus 77% by intention to treat (p= 0.08) and 73%versus 91% in the per
      protocol analysis (p= 0.004). Side effects and compliance in the two groups were
      comparable. CONCLUSIONS: Seven- and 10-day triple therapies seem equally
      efficient in peptic ulcer patients. In contrast, 7-day therapy is significantly
      less effective in nonulcer dyspepsia patients. Ten-day therapy, therefore, seems
      preferable when treating nonulcer patients.

PMID- 16086705
TI  - Mechanoreceptors of the proximal stomach and perception of gastric distension.
AB  - OBJECTIVES: To assess the role of tension receptors in gastric perception by
      pharmacologically modifying gastric contractile activity during isovolumetric
      distensions of the proximal stomach with the hypothesis that relaxation decreased
      perception and contraction increased it. METHODS: Fourteen healthy subjects
      underwent two 30-min isovolumetric (75% of the threshold volume for discomfort)
      distensions using a barostat. During the second distension, either gastric
      relaxation was induced by intravenous (i.v.) glucagon 4.8 microg/kg bolus plus
      9.6 microg/kg per h or contraction by i.v. erythromycin 3 mg/kg. Hunger and
      fullness were assessed with a 100-mm analog scale before and at 15 and 30 min
      during each distension. RESULTS: Glucagon decreased baseline intrabag pressure
      (8.4 +/- 1.0 vs 10.7 +/- 1.3 mmHg; p < 0.05) and abolished the pressure waves (0
      vs 16.7 +/- 2.3) when compared with placebo, whereas erythromycin increased
      baseline pressure (13.2 +/- 1.0 vs 11.9 +/- 0.9 mmHg; p < 0.05) and the rate of
      pressure waves (31.7 +/- 5.4 vs 20.5 +/- 3.1; p < 0.05). Fullness increased (p <
      0.05) during distension, but it was unaffected by either of the drugs: Delta
      score (i.e., score during distension--baseline score) of 38 +/- 10 mm (glucagon)
      versus 22 +/- 10 (placebo) and 24 +/- 17 mm (erythromycin) versus 36 +/- 14
      (placebo) at 15 min. Similar observation were made at 30 min. Hunger was
      influenced neither by distension nor by any of the two drugs consistently.
      CONCLUSIONS: Our data do not support a prominent role of tension receptors of the
      proximal stomach on perception of fullness, suggesting that stretch, that is,
      volume, is the more relevant stimulus.

PMID- 16086706
TI  - Impact of Helicobacter pylori infection on gastric and plasma ghrelin dynamics in
      humans.
AB  - OBJECTIVES: There are contradictory reports on the relationship between
      Helicobacter pylori and circulating ghrelin. We sought to clarify the influence
      of H. pylori infection on gastric and plasma ghrelin dynamics in humans. METHODS:
      Using endoscopic biopsies from the corpus of 56 H. pylori-infected patients and
      25 uninfected subjects, ghrelin mRNA expression levels and gastric ghrelin
      peptide contents were measured by real-time polymerase chain reaction and
      radioimmunoassay, respectively. We also measured plasma ghrelin concentrations
      and analyzed the numbers of ghrelin immunoreactive cells in the fundic gland
      area. Fifty-one patients with H. pylori infection were treated with a 7-day
      triple therapy consisting of lansoprazole, clarithromycin, and amoxicillin.
      RESULTS: The gastric ghrelin mRNA expression level of H. pylori-positive patients
      (1.64 +/- 1.27 in arbitrary units) was significantly lower than in H. pylori
      negative subjects (4.87 +/- 4.1, p < 0.0001). A similar trend was noted for
      ghrelin peptide contents (31.2 +/- 27.5 vs 81.2 +/- 64.1 ng/mg protein,
      respectively, p < 0.0001). There was no significant difference in the number of
      ghrelin immunoreactive cells/mm(2) in terms of H. plyori status. Plasma ghrelin
      concentrations in H. pylori-infected patients (144.6 +/- 7.8.8 fmol/ml) were
      significantly lower than in uninfected subjects (196.1 +/- 97.2, p < 0.05) and
      increased following cure of the infection. Plasma ghrelin levels correlated
      positively with the expression levels of ghrelin mRNA (r = 0.583, p < 0.0001) and
      peptide products (r = 0.574, p < 0.0001). There was a significant stepwise
      decrease in gastric ghrelin mRNA expression (p < 0.05), peptide contents (p <
      0.01) and density of ghrelin immunoreactive cells (p < 0.05) with progression of
      histological severity of glandular atrophy in the corpus. The histological
      severity of chronic inflammation also negatively influenced the ghrelin mRNA
      expression (p < 0.001) and peptide production (p < 0.005). CONCLUSIONS: H. pylori
      infection has a negative impact on gastric and plasma ghrelin dynamics. Chronic
      inflammatory and atrophic changes associated with the infection may affect
      gastric ghrelin biosynthesis and contribute to the low circulating levels.

PMID- 16086707
TI  - Bravo capsule placement in the gastric cardia: a novel method for analysis of
      proximal stomach acid environment.
AB  - BACKGROUND: Intragastric pH monitoring is currently done using catheter-based pH
      systems. This study assessed the feasibility of proximal intragastric pH
      recording with the Bravo wireless pH monitoring system using novel methodology.
      METHODS: Nine asymptomatic volunteers and 9 symptomatic patients were studied.
      One pH capsule was positioned under direct endoscopic visualization so that the
      device straddled the squamocolumnar junction (SCJ) with the attachment well
      positioned on squamous mucosa and the pH electrode 1.5-2 cm distal to the SCJ. A
      second capsule was placed 6 cm proximal to the SCJ. The signal from each capsule
      was recorded by a separate receiver synchronized for time. RESULTS: Successful
      placement and interpretable recording for >42 h from both pH capsules was
      achieved in 16 (88%) of 18 subjects. Data capture were 98.3% in the cardia and
      97.7% in the esophagus. Two failures occurred due to premature capsule detachment
      (one esophageal and one gastric). The acid environment in the cardia was similar
      in asymptomatic controls and symptomatic patients and exhibited less meal-related
      buffering than is typical of more distal intragastric recordings. In addition,
      nadir gastric cardia pH was almost always less than nadir esophageal pH during
      reflux events. CONCLUSIONS: Twenty-four hour gastric cardia pH monitoring is
      feasible with the Bravo system and can be added to esophageal pH monitoring to
      assess concomitant cardia acidity. Instantaneous cardia pH defines the potential
      nadir esophageal pH during reflux events.

PMID- 16086708
TI  - Safety of wireless capsule endoscopy in patients with implantable cardiac
      defibrillators.
AB  - OBJECTIVES: Wireless video capsule endoscopy (CE) is a new technology that allows
      visualization of the entire small intestinal mucosa. It is indicated for the
      evaluation of obscure gastrointestinal bleeding (OGIB) and other disorders of the
      small intestine. Studies to date suggest that CE is safe and associated with few
      adverse events. A concern, which has not been studied, is the potential effect of
      CE on implanted cardiac devices such as implantable cardiac defibrillators (ICD)
      and other electromedical devices. We previously found CE to be safe in patients
      with cardiac pacemakers. The primary aim of this study was to evaluate the safety
      of CE in patients with ICDs who were being evaluated for OGIB. In addition, a
      secondary aim of the study was to determine whether ICDs had any effect on the
      images captured by CE. METHODS: Patients referred for the evaluation of OGIB and
      who also had an ICD were enrolled into the study after informed consent. Five
      consecutive patients (four females and one male; mean age: 72 yr; range: 60-81
      yr) with ICDs were studied. All patients had transvenous endocardial ICDs located
      in the chest. Prior to CE, patients had a baseline electrocardiogram (ECG) and
      ICD interrogation. Thereafter, CE was performed in a hospital setting with
      telemetry monitoring performed simultaneously. A post-procedure ICD interrogation
      was carried out to evaluate changes in programmed parameters. A cardiologist and
      ICD nurse specialist together reviewed both the telemetry monitor and the post
      procedure ICD interrogation on each patient. When CE studies were reviewed,
      observations pertaining to technical difficulties and interference with video
      imaging were documented. RESULTS: No arrhythmia or other adverse cardiac events
      were noted during capsule transmission. No interference by the ICD on the CE
      video images was seen. CONCLUSIONS: CE was performed safely in these five
      patients with ICDs, and was not associated with any adverse cardiac events. ICDs
      also do not appear to interfere with video capsule imaging.

PMID- 16086709
TI  - Capsule endoscopy versus standard tests in influencing management of obscure
      digestive bleeding: results from a German multicenter trial.
AB  - BACKGROUND: Capsule endoscopy (CE) is a new modality for obscure digestive
      bleeding (OBD), but little is known about its influence on management and
      outcome. PATIENTS AND METHODS: Fifty-six patients (male/female 26/30; mean age 63
      yr) with ODB, and negative upper and lower gastrointestinal (GI) endoscopy were
      included in this multicenter study. The diagnostic yield of CE was compared to
      three other tests (OT: push enteroscopy, enteroclysis, angiography), and patients
      were followed up for at least 6 months. Parameters were analyzed that led to
      major management changes such as surgical or endoscopic intervention or specific
      medical therapy, as well as their correlation to further bleeding. RESULTS: CE
      had a diagnostic yield higher than OT (68% vs 38%). Major management changes and
      an improvement in bleeding activity were observed in 21 and 44 patients,
      respectively. The number and type of positive findings on CE were associated with
      significant management changes (p < 0.05). The number of positive findings
      detected by CE as well as by OT correlated with further bleeding episodes (p <
      0.05). However, clinical parameters (lowest hemoglobin (Hb) value, number of
      blood transfusions) were also significantly associated with outcome. Diagnoses of
      specific diseases (tumor, Crohn, NSAID ulcer) by CE led to a favorable outcome in
      64% of cases, whereas negative CE cases were associated with no further bleeding
      in 80%. CONCLUSION: CE helps with management decisions and can replace other more
      complex and risky standard tests. Nevertheless, clinical parameters are equally
      important for predicting further bleeding and should also be used to decide on
      further management.

PMID- 16086710
TI  - Endoscopic ultrasound guided therapy of benign and malignant biliary obstruction:
      a case series.
AB  - OBJECTIVES: Endoscopic retrograde cholangiography is an established method for
      treatment of common bile duct stones as well as for palliation of patients with
      malignant pancreaticobiliary strictures. It may be unsuccessful in the presence
      of a complex peripapillary diverticulum, prior surgery, obstructing tumor,
      papillary stenosis, or impacted stones. Percutaneous transhepatic biliary
      drainage and surgery are alternative methods with a higher morbidity and
      mortality in these cases. Recently, endoscopic ultrasound (EUS) guided biliary
      stent placement has been described in patients with malignant biliary
      obstruction. We describe our experience with this method that was also used for
      the treatment of cholangiolithiasis for the first time. METHODS: The EUS guided
      transduodenal puncture of the common bile duct with stent placement was performed
      in 5 patients. In 2 of these patients, the stents were removed after several
      weeks and common bile duct stones were extracted. In another patient with
      gastrectomy, the left intrahepatic bile duct was punctured transjejunally and a
      metal stent was introduced transhepatically to bridge a distal common bile duct
      stenosis. RESULTS: Biliary decompression was successful in all 6 patients. No
      immediate complications occurred. One patient developed a subacute phlegmonous
      cholecystitis. CONCLUSIONS: Interventional EUS guided biliary drainage is a new
      technique that allows drainage of the biliary system in benign and malignant
      diseases when the bile duct is inaccessible by conventional ERCP.

PMID- 16086711
TI  - Hepatitis B virus DNA integration in hepatocellular carcinoma after interferon
      induced disappearance of hepatitis C virus.
AB  - OBJECTIVES: Hepatocellular carcinoma (HCC) has been reported in patients in whom
      hepatitis C virus (HCV) was eliminated by interferon (IFN) therapy. We examined
      the pathogenesis of HCC in patients with sustained viral response. METHODS:
      Operable HCC developed in 7 of 342 patients cured of HCV infection by IFN
      monotherapy. No patient abused alcohol or had diabetes mellitus or obesity.
      Resected specimens of HCC were histologically evaluated. DNA extracted from HCC
      was examined by polymerase chain reaction (PCR) to locate hepatitis B virus (HBV)
      DNA. HBV integration sites in human genome were identified by cassette-ligation
      mediated PCR. RESULTS: HBV DNA was not amplified in serum samples from any of the
      seven patients with HCC and was found in liver in four patients. In the latter
      four patients, HBV DNA was integrated into the human genome of HCC. In two of
      these patients, covalently closed circular HBV (cccHBV) was also detected. The
      patients with HBV DNA integration were free of HCV for more than 3 yr. In two of
      the three patients without HBV DNA integration, the surrounding liver showed
      cirrhosis. The liver of HCC with HBV DNA integration had not progressed to
      cirrhosis. Three of the four tumors with HBV integration had one integration site
      each, located at chromosomes 11q12, 11q22-23, and 22q11, respectively. The other
      tumor had two integration sites, situated at chromosomes 11q13 and 14q32. At
      chromosome 11q12, HBV DNA was integrated into protein-coding genome, the function
      of which remains unclear. CONCLUSION: Integrated HBV DNA may play a role in
      hepatocarcinogenesis after the clearance of HCV by IFN treatment.

PMID- 16086712
TI  - UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with
      hepatocellular carcinoma risk and onset age.
AB  - OBJECTIVES: It has been demonstrated that the UDP-glucuronosyltransferase (UGT)
      1A7*3 allele is a risk factor for hepatocellular carcinoma (HCC) in German and
      Japanese populations. In this study, therefore, we evaluated the association
      between UGT1A7 genetic polymorphisms and HCC risk in southern Taiwan, where
      hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are endemic.
      METHODS: The 217 HCC patients and 291 controls enrolled in this case-control
      study were genotyped for UGT1A7 polymorphisms using polymerase chain reaction
      restriction fragment length polymorphism. RESULTS: Univariate logistic regression
      analysis revealed that presence of UGT1A7*2 and *3 alleles was associated with
      HCC risk [odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.04
      approximately 2.16 and OR = 1.73, 95% CI: 1.19 approximately 2.52, respectively].
      Multiple logistic regression analysis demonstrated that significant independent
      risk factors for HCC were male gender (OR = 2.53, 95% CI: 1.42 approximately
      4.52), HBV infection (OR = 13.73, 95% CI: 8.04 approximately 23.46), HCV
      infection (OR = 83.93, 95% CI: 37.01 approximately 190.32), and low-activity
      UGT1A7 genotype [high/low (H/L) genotype: OR = 1.93, 95% CI: 1.12 approximately
      3.32; low/low (L/L) genotype: OR = 3.06, 95% CI: 1.50 approximately 6.24]. For
      male HCC patients, significantly earlier onset age was observed for those bearing
      the UGT1A7 low-activity genotype as opposed to those with the high-activity
      analogue (median age: 50 vs 59 yr; p < 0.05). CONCLUSIONS: An inverse dose
      response relationship was demonstrated between the detoxifying activity of the
      UGT1A7 genotypes and HCC. Of the male HCC patients, median onset age for those
      carrying an UGT1A7 low-activity genotype was 9 yr lower than those bearing the
      high-activity variant.

PMID- 16086713
TI  - Comparison of the usefulness of three staging systems for hepatocellular
      carcinoma (CLIP, BCLC, and JIS) in Japan.
AB  - OBJECTIVES: We retrospectively compared the usefulness of three different staging
      systems for hepatocellular carcinoma (HCC), the Cancer of the Liver Italian
      Program (CLIP) scoring system, the Barcelona Clinic Liver Cancer (BCLC)
      classification system, and the Japan Integrated Staging (JIS) system, in terms of
      patient distribution and survival rates. METHODS: Subjects were 1,508 patients
      diagnosed as having initial HCC during the period of 1976-2003. The disease was
      staged in all patients by means of the three staging systems, and the
      distribution of patients across stages and associated survival rates were
      compared between systems. In addition, comparisons were made on the basis of the
      time of diagnosis: 1976-1990 (n = 497) and 1991-2003 (n = 1,011). RESULTS:
      Patients were evenly distributed across stages within each staging system, and
      survival rates differed between stages except for BCLC C and D. During the period
      1991-2003, when HCCs were smaller at diagnosis, JIS system is in particular
      yielded even distribution of patient across stages and marked differences in
      survival rates. CONCLUSIONS: Overall, the CLIP and the JIS scoring systems proved
      to be suitable for patients in Japan with HCC. The CLIP staging systems proved to
      be more suitable before 1991. In contrast, the JIS system was the most suitable
      after 1990, when early detection and early treatment of HCC became common. The
      JIS system is, therefore, the appropriate system in this era of early detection
      and treatment of HCC.

PMID- 16086714
TI  - Prospective multicenter study of eligibility for antiviral therapy among 4,084
      U.S. veterans with chronic hepatitis C virus infection.
AB  - BACKGROUND: Many veterans may not be candidates for hepatitis C virus (HCV)
      treatment due to contraindications to therapy. The aims of this study were to
      determine the proportion of HCV-infected veterans who were eligible for
      interferon alfa and ribavirin therapy and to evaluate barriers to HCV treatment.
      METHODS: We prospectively enrolled 4,084 veterans who were referred for HCV
      treatment over a 1-yr period at 24 Veterans Affairs (VA) Medical Centers.
      Treatment candidacy was assessed using standardized criteria and the opinion of
      the treating clinician. RESULTS: Overall, 32.2% (95% CI, 30.8-33.7%) were
      candidates for HCV treatment according to standardized criteria, whereas 40.7%
      (95% CI, 39.2-42.3%) were candidates in the opinion of the treating clinician.
      Multivariable analysis identified ongoing substance abuse (OR = 17.68; 95% CI,
      12.24-25.53), comorbid medical disease (OR = 9.62; 95% CI, 6.85-13.50),
      psychiatric disease (OR = 9.45; 95% CI, 6.70-13.32), and advanced liver disease
      (OR = 8.43; 95% CI, 4.42-16.06) as the strongest predictors of not being a
      treatment candidate. Among patients who were considered treatment candidates,
      76.2% (95% CI, 74.0-78.3%) agreed to be treated and multivariable analysis showed
      that persons >/=50 yr of age (OR = 1.37; 95% CI, 1.07-1.76) and those with >50
      lifetime sexual partners (OR = 1.44; 95% CI, 1.08-1.93) were more likely to
      decline treatment. CONCLUSIONS: The majority of veteran patients are not suitable
      candidates for HCV treatment because of substance abuse, psychiatric disease, and
      comorbid medical disease, and many who are candidates decline therapy.
      Multidisciplinary collaboration is needed to overcome barriers to HCV therapy in
      this population.

PMID- 16086715
TI  - Budesonide for maintenance of remission in patients with Crohn's disease in
      medically induced remission: a predetermined pooled analysis of four randomized,
      double-blind, placebo-controlled trials.
AB  - OBJECTIVES: To evaluate the efficacy and safety of oral budesonide for
      maintenance of remission in patients with mild to moderately active Crohn's
      disease (CD) of the ileum and/or ascending colon. METHODS: Four double-blind,
      placebo-controlled trials with identical protocols were combined according to a
      predetermined analysis plan. Three hundred eighty patients with CD in medically
      induced remission (CD activity index [CDAI]< or =150) were randomized to receive
      oral budesonide 3 mg, 6 mg, or placebo daily for 12 months. The primary outcome
      measure was time to relapse (increase in CDAI of 60 points above baseline and
      >150). RESULTS: The median time to relapse was 268, 170, and 154 days for
      budesonide 6 mg, budesonide 3 mg, and placebo groups, respectively (p= 0.0072).
      The frequency of adverse events and glucocorticosteroid side effects were similar
      in all groups. CONCLUSION: Budesonide 6 mg/day is effective for prolonging time
      to relapse and for significantly reducing rates of relapse at 3 and 6 months but
      not 12 months in patients with CD in medically induced remission.

PMID- 16086716
TI  - Depletion of immunoglobulin M memory B cells is associated with splenic
      hypofunction in inflammatory bowel disease.
AB  - OBJECTIVES: IgM memory B cells that are responsible for the protection against
      infections by encapsulated bacteria, require the spleen for their generation
      and/or survival. Since the association between inflammatory bowel disease and
      functional hyposplenism is well described, our aim was to verify whether IgM
      memory B cells mirror the reduced splenic function in Crohn's disease and
      ulcerative colitis patients. METHODS: Peripheral blood samples were obtained from
      32 Crohn's disease and 29 ulcerative colitis patients, 33 healthy controls, and
      27 splenectomized patients. Perendoscopic intestinal biopsies were also collected
      from 15 of 32 Crohn's disease patients, 14 of 29 ulcerative colitis patients and
      13 of 33 control subjects. Counting of erythrocytes with membrane abnormalities
      (pitted red cells) was used as an indicator of splenic function and flow
      cytometry was performed to analyze both peripheral and mucosal B cells. RESULTS:
      Twelve of 32 Crohn's disease patients and 13 of 29 ulcerative colitis patients
      had pitted red cell values >4% and were considered to be hyposplenic. In
      inflammatory bowel disease patients circulating IgM memory B cells were
      significantly lower than in control subjects. We observed a significant inverse
      correlation between the frequency of circulating IgM memory B cell and the pitted
      red cell values in inflammatory bowel disease patients with hyposplenism. To
      exclude the possibility that the reduction of circulating IgM memory B cells
      reflected their recruitment in the inflamed bowel mucosa, lamina propria B-cell
      populations were also characterized. We found that the frequency of IgM memory B
      cells was similar in the blood and in the lamina propria of the same patient.
      CONCLUSIONS: Our findings show that peripheral IgM memory B cells are reduced in
      inflammatory bowel disease patients and this defect seems to be related to the
      impairment of splenic function.

PMID- 16086717
TI  - Heightened responses to stressors in patients with inflammatory bowel disease.
AB  - OBJECTIVES: Several studies suggest that stressful situations (stressors) worsen
      the course of inflammatory bowel disease (IBD), but the mechanism is not known.
      Based on several lines of evidence, we hypothesized that psychosocial stress
      activates the brain-gut axis (BGA) and mucosal mast cells (MC), and activated MC
      produce proinflammatory cytokines. To test this hypothesis, we determined whether
      stressor-induced activation of BGA is exaggerated in IBD patients. METHODS:
      Stress was induced in 15 IBD patients who were in remission (inactive IBD) and in
      seven controls by a widely used stressor, the cold pressor test (CPT), daily for
      five consecutive days. Induction of stress was confirmed objectively by
      measurement of stress hormones (serum cortisol and ACTH), and hemodynamic
      parameters and subjectively by questionnaire. Activation of the BGA by this
      stressor was assessed by evaluating colonic mucosal MC histology and
      degranulation, using electron microscopy (EM). The effects of the stressor on the
      intestinal mucosa were assessed by changes in inflammatory cell histology,
      epithelial mitochondria (EM), and oxidative tissue injury (assays for protein
      oxidation). RESULTS: In both study groups, the stressor resulted in (1) increased
      levels of stress hormones, (2) the expected changes in hemodynamic parameters,
      (3) activation and degranulation of MC, (4) mitochondrial damage to epithelial
      cells, and (5) mucosal protein oxidation. These changes were more marked in IBD
      patients. CONCLUSIONS: The heightened response to the stressors and the greater
      epithelial damage in IBD patients suggests that stress-induced activation of the
      BGA and of mucosal MC is important in the initiation and/or flare up of IBD.

PMID- 16086718
TI  - Colorectal cancer screening in HIV-infected patients 50 years of age and older:
      missed opportunities for prevention.
AB  - OBJECTIVES: Although human immunodeficiency virus (HIV)-infected patients are now
      living longer, there are no published data on colorectal cancer (CRC) screening
      in this population. We hypothesized that HIV-infected patients were less likely
      to be screened for CRC compared to patients without HIV. METHODS: Consecutive HIV
      infected patients > or =50 yr old seen in our outpatient clinic from 1/1/01 to
      6/30/02 were identified. For each HIV-infected patient, we selected one age- and
      gender-matched control subject without HIV infection who was seen during the same
      time period. The electronic medical records were reviewed to determine the
      proportion of patients that had a fecal occult blood test (FOBT), flexible
      sigmoidoscopy, air-contrast barium enema (ACBE), or colonoscopy. RESULTS: During
      the 18-month study period, 538 HIV-infected outpatients were seen and 302 (56.1%)
      were > or =50 yr old. Despite significantly more visits with their primary care
      provider, HIV-infected patients were less likely to have ever had at least one
      CRC screening test (55.6%vs 77.8%, p < 0.001). The proportion of HIV-infected
      patients who ever had a FOBT (43.0%vs 66.6%, p < 0.001), flexible sigmoidoscopy
      (5.3%vs 17.5%, p < 0.001), ACBE (2.6%vs 7.9%, p= 0.004), or colonoscopy (17.2%vs
      27.5%, p= 0.002) was significantly lower than in control subjects. In addition,
      HIV-infected patients were significantly less likely to be up-to-date with at
      least one CRC screening test according to current guidelines (49.3%vs 65.6%, p <
      0.001). CONCLUSIONS: A substantial number of HIV-infected patients are > or =50
      yr of age and CRC screening is underutilized in this population. Public health
      strategies to improve CRC screening in HIV-infected patients are needed.

PMID- 16086719
TI  - Cholecystectomy and the risk of colorectal cancer.
AB  - OBJECTIVES: Cholecystectomy has been implicated as a possible risk factor for
      colorectal cancer. However, the clinical evidence and the underlying mechanism
      for this association are still inconclusive. We conducted a population-based
      study to further clarify this association. METHODS: We conducted a retrospective
      cohort study among all patients aged 40 yr or older in the General Practice
      Research Database from the United Kingdom. We excluded patients with <1 yr of
      colorectal cancer-free database follow-up as well as those patients who developed
      colorectal cancer within 1 yr after their cholecystectomies. Crude and adjusted
      incidence rate ratios (IRRs) were determined using Poisson regression. RESULTS:
      The incidence rate of colorectal cancer among cholecystectomy patients (n =
      55,960) was 119 (95% CI: 106-133) per 100,000 person-years, compared to 86 (95%
      CI: 83-90) per 100,000 person-years among patients without a cholecystectomy (n =
      574,668). Among the covariates examined, only sex and age were significant
      confounders and were included in the adjusted analyses. The adjusted IRR of
      colorectal cancer associated with cholecystectomy was 1.32 (95% CI: 1.16-1.48, p
      < 0.001). The positive association was present for colon cancer (adjusted IRR
      1.51, 95% CI: 1.30-1.74, p < 0.001), but not for rectal cancer (adjusted IRR
      1.00, 95% CI: 0.85-1.17, p= 0.99). The pattern of association was similar in men
      versus women. A similar association with colon cancer was observed for
      cholelithiasis. CONCLUSIONS: Cholecystectomy is associated with a modestly
      increased risk of colon cancer but not for rectal cancer. Lithogenic bile could
      be the underlying mechanism.

PMID- 16086720
TI  - Validation of a clinical prediction rule for severe acute lower intestinal
      bleeding.
AB  - OBJECTIVES: Acute lower intestinal bleeding is a heterogeneous disorder and
      identification of high-risk patients is challenging. We previously
      retrospectively identified predictors of severity in patients with acute lower
      intestinal bleeding. The aim of this study was to prospectively validate a
      clinical prediction rule for severe acute lower intestinal bleeding. METHODS:
      This was a prospective, observational cohort study of consecutive patients
      admitted to an academic, tertiary care or a community-based teaching hospital for
      management of acute lower intestinal bleeding. Data were collected on seven
      previously identified predictors of severe bleeding: heart rate > or = 100/min,
      systolic blood pressure < or = 115 mmHg, syncope, nontender abdominal exam,
      rectal bleeding in the first 4 h of evaluation, aspirin use, and >2 comorbid
      conditions. Severe bleeding was defined as transfusion of > or =2 units of red
      blood cells, and/or a decrease in hematocrit of > or =20% in the first 24 h,
      and/or recurrent rectal bleeding after 24 h of stability (accompanied by a
      further decrease in hematocrit of > or =20%, and/or additional blood
      transfusions, and/or readmission for acute lower intestinal bleeding within 1 wk
      of discharge). Patients were stratified into 3 risk groups according to the
      previously developed prediction rule: low (no risk factors), moderate (1-3 risk
      factors), and high (>3 risk factors). RESULTS: A total of 275 patients with acute
      lower intestinal bleeding were identified. The risk of severe bleeding in each
      risk category was similar in the validation and derivation cohorts (p values
      >0.05): low risk 6%versus 9%, moderate risk 43%versus 43%, and high risk
      79%versus 84%. The area under the receiver operating characteristic curve was
      0.754 for the validation cohort and 0.761 for the derivation cohort. The
      magnitude of the risk score was significantly correlated with major clinical
      outcomes including surgery, death, blood transfusions, and length of stay.
      CONCLUSION: We have developed and prospectively validated a clinical prediction
      rule for acute severe lower intestinal bleeding. This prediction rule could
      improve the triage of patients to appropriate levels of care and interventions,
      and guide a more standardized approach to acute lower intestinal bleeding.

PMID- 16086721
TI  - Nosocomial antibiotic-associated diarrhea associated with enterotoxin-producing
      strains of methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVES: The aim of this study is to present new evidence that enterotoxin
      producing strains of methicillin-resistant Staphylococcus aureus may cause
      nosocomial antibiotic-associated diarrhea. METHODS: We conducted a prospective
      study that utilized standard methods to exclude other bacterial, parasitic, and
      viral pathogens as causes of nosocomial diarrhea in patients with heavy growth of
      methicillin-resistant S. aureus in their stool. Staphylococcal enterotoxin assays
      were performed on S. aureus strains recovered from patients' stools and on stool
      specimens from affected patients. Retrospective cohort studies compared the
      severity of diarrhea in patients with methicillin-resistant S. aureus-associated
      diarrhea with that of patients whose stool did not contain the organism and with
      patients colonized or infected with enterotoxin-negative methicillin-resistant S.
      aureus strains. RESULTS: During an 18-month period, 11 patients had nosocomial
      antibiotic-associated diarrhea associated with enterotoxin-producing strains of
      methicillin-resistant S. aureus. Other common bacterial, parasitic, and viral
      pathogens were excluded. S. aureus strains from the 11 patients produced
      staphylococcal enterotoxin A, A and B, or D. Eighty-nine percent of patients had
      the same enterotoxin(s) in stool specimens as produced by the strain recovered
      from their stool. Case patients had a greater number of days of diarrhea than
      patients without methicillin-resistant S. aureus in their stool (p < 0.001), or
      randomly selected patients colonized or infected with enterotoxin-negative
      methicillin-resistant S. aureus (p < 0.001). CONCLUSIONS: Our findings provide
      evidence that enterotoxin-producing strains of methicillin-resistant S. aureus
      may cause nosocomial antibiotic-associated diarrhea. Greater recognition of this
      disease should result in more rapid and appropriate treatment of affected
      patients.

PMID- 16086722
TI  - Matrix metalloproteinases expression correlates with survival in patients with
      esophageal squamous cell carcinoma.
AB  - OBJECTIVES: The matrix metalloproteinases (MMPs) are a family of zinc-dependent
      endopeptidases capable of degrading the extracellular matrix and play important
      roles in malignancies. We evaluated the expression of four MMPs in esophageal
      squamous cell carcinoma (ESCC), and assessed the association between MMP
      expression and clinicopathologic characteristics and disease-free survival time.
      METHODS: We evaluated MMP1, MMP7, MMP9, and MMP13 expression in tissues from 208
      patients with ESCC using immunohistochemistry (IHC), and correlated MMP
      expression to clinicopathologic characteristics and disease-free survival time.
      To confirm MMP9 expression at different levels, we simultaneously performed RT
      PCR, Western blotting, and IHC on tissues from a separate cohort of 23 patients
      with ESCC. RESULTS: IHC analysis showed that 63.0%, 41.8%, 49.0%, and 32.2% of
      208 ESCC samples were positive for MMP1, MMP7, MMP9, and MMP13, respectively.
      MMPs were strongly expressed in the cytoplasm of cancer cells, especially in the
      invasive margin, and weakly expressed in stromal cells. No immunostaining was
      detected in non-cancerous esophageal mucosa. MMP9 expression was positively
      associated with poor tumor cell differentiation (p= 0.001), vessel permeation (p=
      0.027), and lymph node metastasis (p= 0.027). MMP9 expression was a negative,
      independent predictor of disease-free survival time (Hazard ratio, 1.470; 95% CI,
      1.105 approximately 1.955; p= 0.008). The expression of MMP7 (median survival
      time: 23 months for MMP7 positive patients, >77 months for MMP7 negative
      patients; p= 0.001) and MMP13 (median survival time: 18 months for MMP13 positive
      patients, 39 months for MMP13 negative patients; p= 0.014) correlated negatively
      with disease-free survival in relatively early stage ESCC patients. Co-expression
      of MMP7, MMP9, and MMP13 in relatively early stage ESCC samples identified
      patients with a poor prognosis (13 months median survival time) compared to those
      lacking MMP7, MMP9, and MMP13 expression (58 months median survival time, p <
      0.001). CONCLUSIONS: MMP9 expression is a negative, independent prognostic factor
      in ESCC and correlates with tumor cell differentiation, vessel permeation, and
      lymph node metastasis. MMP7, MMP9, and MMP13 may function in early stage ESCC,
      and their co-expression predicts poor outcome for relatively early stage ESCC
      patients.

PMID- 16086723
TI  - Antireflux surgery outcomes in pediatric gastroesophageal reflux disease.
AB  - OBJECTIVES: Antireflux surgery is performed frequently in children with
      gastroesophageal reflux disease (GERD). Few comparative studies exist which
      assess the indications for and short- or long-term outcome of open Nissen
      fundoplication (ONF) and laparoscopic Nissen fundoplication (LNF) for pediatric
      GERD. We investigated the frequency of reoperation and factors that might
      influence its occurrence. METHODS: We performed a retrospective, follow up cohort
      study of all children </=5 years, who underwent LNF or ONF at our institution
      from January 1, 1997 to December 31, 2002, where five pediatric surgeons perform
      fundoplication. Mean follow up time was 36.2 months. The following information
      was obtained: surgical indications, hospital course data, and long-term surgical
      outcomes. Data were analyzed using univariate and multiple logistic regressions.
      RESULTS: Overall, 456 (150 [32.9%] ONF vs. 306 [67.1%] LNF) cases were analyzed.
      Reoperation was performed in 55 (12.06%), LNF 43 (14.05%), and ONF 12 (8%). The
      mean interim to reoperation for LNF was 11 months compared to 17 months for ONF
      (p= 0.007). The reoperation rate at 12 and 24 months were 10.5%, 13.4% and 4%,
      6.7% respectively, when LNF was compared to ONF (p= 0.01). The multivariate
      analysis showed that initial LNF and prematurity were the main predictors for
      reoperation. CONCLUSIONS: The majority of reoperations for both LNF and ONF
      occurred in the first year after initial operation; LNF had a significantly
      higher reoperation rate than ONF. The probability of reoperation for LNF and ONF
      increases with the presence of comorbidities, especially prematurity and chronic
      respiratory conditions.

PMID- 16086724
TI  - The epidemiology of childhood recurrent abdominal pain in Western countries: a
      systematic review.
AB  - OBJECTIVE: Recurrent abdominal pain (RAP) of childhood is a common problem
      encountered by clinicians. The aim of this study was to systematically review
      published literature about the prevalence, incidence, natural history, and co
      morbid conditions of childhood RAP in western countries. METHODS: A computer
      assisted search of MEDLINE, EMBASE, and Current Contents/Science Edition
      databases was performed. Study selection criteria included: (1) United States and
      European population and school-based samples of children; (2) diagnostic criteria
      of RAP; and (3) published in full manuscript form in English. Data were
      extracted, tabulated, and presented in descriptive form. RESULT: The prevalence
      of RAP ranged from 0.3 to 19% (median 8.4; IQR 2.3-14.7). Published studies in
      children demonstrate a higher prevalence of RAP in females, with the highest
      prevalence of symptoms between 4 and 6 yr and early adolescence. Identified
      studies demonstrated associations between RAP and the child's familial and
      socioeconomic environment. In addition, childhood RAP was reported to be
      associated with psychological co-morbidity in childhood and adulthood.
      Population/school-based studies have not, however, established the incidence of
      this disorder, what features predict long-standing symptoms, or whether RAP is a
      risk factor for adult functional bowel disorders. CONCLUSION: RAP is a common
      complaint of childhood with associated familial, psychological, and co-morbid
      conditions. Epidemiologic studies of RAP in children may offer information on the
      evolution of functional bowel disorders through the lifespan.

PMID- 16086725
TI  - Colchicine for primary biliary cirrhosis: a Cochrane Hepato-Biliary Group
      systematic review of randomized clinical trials.
AB  - OBJECTIVES: Colchicine is used for patients with primary biliary cirrhosis due to
      its immunomodulatory and antifibrotic potential. The results from randomized
      clinical trials have, however, been inconsistent. We conducted a systematical
      review to evaluate the effect of colchicine for primary biliary cirrhosis.
      METHODS: We identified randomized clinical trials comparing colchicine with
      placebo/no intervention. We analyzed effects by fixed and random effects model.
      We investigated heterogeneity by subgroup and sensitivity analyses. RESULTS: We
      included 10 trials involving 631 patients, four of which were high-quality
      trials. No significant differences were detected between colchicine and
      placebo/no intervention regarding mortality (relative risk (RR), 1.21; 95%
      confidence interval (CI), 0.71-2.06), mortality or liver transplantation (RR =
      1.00; 95% CI, 0.67-1.49), liver complications, liver biochemical variables, liver
      histology, or adverse events. Regarding mortality, an extreme case analysis
      favoring colchicine did not demonstrate beneficial effects of colchicine, whereas
      an extreme case analysis favoring placebo/no intervention demonstrated a
      detrimental effect of colchicine (RR = 2.28; 95% CI, 1.17-4.44). The number of
      patients without improvement of pruritus significantly decreased in the
      colchicine group (RR = 0.75; 95% CI, 0.65-0.87). However, this estimate was based
      on only 156 patients from three trials. CONCLUSIONS: There is insufficient
      evidence to support the use of colchicine for patients with primary biliary
      cirrhosis. As we are unable to exclude a risk of increased mortality, we
      recommend to use colchicine only in randomized clinical trials.

PMID- 16086727
TI  - ASGE versus EPAGE versus diagnostic yield: a level playing field, please!

PMID- 16086728
TI  - Esophageal pH monitoring on PPI therapy: removing the blinders.

PMID- 16086729
TI  - Lack of financial benefit of inpatient percutaneous endoscopic gastrostomy tube
      placement.

PMID- 16086731
TI  - Sildenafil-associated hepatotoxicity.

PMID- 16086732
TI  - GI tuberculosis and histoplasmosis in an HIV (+) patient presenting with lower GI
      bleeding.

PMID- 16086733
TI  - Safety of high doses of mesalazine during pregnancy.

PMID- 16086734
TI  - Toxic epidermal necrolysis: current evidence, practical management and future
      directions.
AB  - Toxic epidermal necrolysis (TEN) is a rare disorder characterized by extensive
      epidermal death. Almost all cases appear to be caused by an idiosyncratic drug
      reaction. Proposed pathogenic mechanisms are conflicting, and the evidence for
      the benefits of individual treatments is inadequate, and in some cases
      contradictory. The mortality rate remains high. We review the literature
      pertaining to the pathogenesis of TEN and drug reactions in general. The
      rationale for therapeutic interventions, together with reported evidence of
      efficacy, are considered. We present a composite model of TEN, based on previous
      work and suggested pathogeneses of TEN, mechanisms of drug reactions and reported
      cytotoxic lymphocyte (CTL) cytolytic pathways. In this system, TEN, like some
      other cutaneous drug eruptions, is an HLA class I-restricted, specific drug
      sensitivity, resulting in clonal expansion of CD8+ CTLs. Cytotoxicity is mediated
      by CTL granzyme and possibly death receptor (DR) ligand (DR-L), probably Fas
      ligand (FasL). Particular to TEN, there is then an amplification sequence
      involving further DR-L expression. FasL is likely to be particularly important
      but tumour necrosis factor (TNF) may well contribute, via the TNF receptor 1 (TNF
      R1) death pathway. Alternatively, we suggest the possibility of upregulation of
      an antiapoptotic TNF-R1-nuclear factor kappaB pathway, which would proscribe
      treatments which downregulate this pathway. None of the published data on
      individual treatment efficacies is sufficiently strong to suggest a definitive
      single treatment. Currently a multifaceted regimen appears indicated, targeting
      various likely intermediary mechanisms, including elimination of residual drug,
      immunosuppression, inhibition of DR pathways, general antiapoptotic strategies,
      and aggressive supportive care. Particular attention has been directed at
      avoiding potential conflicts between different treatments and avoiding agents
      that theoretically might have a net proapoptotic rather than antiapoptotic
      effect. Nursing on a specialized unit is of paramount importance.

PMID- 16086735
TI  - Thalidomide: dermatological indications, mechanisms of action and side-effects.
AB  - Thalidomide was first introduced in the 1950s as a sedative but was quickly
      removed from the market after it was linked to cases of severe birth defects.
      However, it has since made a remarkable comeback for the U.S. Food and Drug
      Administration-approved use in the treatment of erythema nodosum leprosum.
      Further, it has shown its effectiveness in unresponsive dermatological conditions
      such as actinic prurigo, adult Langerhans cell histiocytosis, aphthous
      stomatitis, Behcet's syndrome, graft-versus-host disease, cutaneous sarcoidosis,
      erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi
      sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis,
      pyoderma gangrenosum and uraemic pruritus. This article reviews the history,
      pharmacology, mechanism of action, clinical uses and adverse effects of
      thalidomide.

PMID- 16086736
TI  - Multiple tissue kallikrein mRNA and protein expression in normal skin and skin
      diseases.
AB  - BACKGROUND: Human tissue kallikreins are a gene family (KLK1-KLK15) encoding for
      15 secretory serine proteases (hK1-hK15). Two tissue kallikrein proteins, hK5 and
      hK7, were previously found in the stratum corneum (SC), stratum granulosum (SG)
      and appendages. hK8 was also shown to be secreted via lamellar granules and
      numerous KLK mRNAs were previously identified. KLKs are believed to be
      responsible for desquamation of corneocytes and sebum, sweat and hair maturation.
      OBJECTIVES: To demonstrate immunohistochemically the expression of hK6, hK8 and
      hK13 in normal skin tissue and to show an increased cell number expressing
      kallikrein mRNAs and proteins in psoriasis vulgaris (PV) and atopic dermatitis
      (AD). METHODS: Samples of normal, PV and AD skin were obtained. hK6-, hK8- and
      hK13-specific antibodies were produced and used for immunohistochemical analysis.
      Multiple KLK mRNAs were synthesized and used for in situ hybridization study.
      RESULTS: Three other hKs, namely hK6, hK8 and hK13, were immunohistochemically
      identified as new skin serine proteases in the whole SC, SG, sebaceous glands,
      eccrine sweat glands, hair follicles and nerves. We also demonstrated an
      increased number of cells expressing KLK mRNAs and hKs in PV and AD. In PV, KLK
      mRNAs/hKs were predominantly expressed in the upper epidermis. In AD, hK
      distribution was rather diffuse and expanded into the lower epidermis.
      CONCLUSIONS: The colocalization of various hKs seems to be essential for the
      regulation of serine protease activity in skin and for steady desquamation and
      skin barrier function. Moreover, the increased number of cells expressing
      multiple KLK mRNA and hK in PV and AD could be a clue to elucidate their
      pathogenesis.

PMID- 16086737
TI  - Role of breast tumour kinase in the in vitro differentiation of HaCaT cells.
AB  - BACKGROUND: Breast tumour kinase (BRK) is a newly identified non-receptor protein
      tyrosine kinase from a metastatic breast tumour. Its biological functions are
      still under extensive investigation. The mouse homologue Sik (Src-related
      intestinal kinase) has been implicated in mouse keratinocyte differentiation;
      however, not much is known about the functions of BRK in human cutaneous biology.
      OBJECTIVES: Using HaCaT cells as an experimental model, to explore the mutual
      relationships between BRK and differentiation of human keratinocytes. METHODS:
      Archival paraffin blocks of normal and pathological skin were retrieved for
      examining the in vivo distribution of BRK. Its expression and subcellular
      localization were examined via indirect immunofluorescence, and quantitative
      changes were analysed by Northern and Western blots. The kinase activity of BRK
      was determined by its autophosphorylation and phosphorylation of exogenous
      substrate in the in vitro kinase assay. Using a retroviral infection method, we
      established stably transfected HaCaT cells expressing vector, wild-type BRK or a
      kinase-defective mutant (K219M). Expression of the differentiation marker keratin
      10 (K10) was compared among these cells using semiquantitative reverse
      transcription-polymerase chain reaction. Results Histochemical examination showed
      that BRK was expressed exclusively in suprabasal keratinocytes. Its distribution
      was both cytoplasmic and intranuclear. An enhanced regional suprabasal expression
      pattern was observed in the confluent areas of cell cultures. The expression of
      BRK transcript and protein was up-regulated in prolonged confluence culture in a
      serum-dependent manner. Its kinase activity was activated shortly after the
      addition of calcium and ionomycin and returned to the basal level within 30 min.
      Overexpression of wild-type BRK moderately promoted the expression of K10
      transcript while the kinase-defective BRK mutant exerted a prominent suppressive
      effect. CONCLUSIONS: The in vivo distribution of BRK and its up-regulation during
      in vitro differentiation of HaCaT cells, together with the activation of its
      kinase activity by calcium/ionomycin and its influence on K10 expression, all
      indicate a role for BRK in the complex process of keratinocyte differentiation.

PMID- 16086738
TI  - Comparative genomic hybridization in extramammary Paget's disease.
AB  - BACKGROUND: Extramammary Paget's disease (EMPD) is a distinct skin cancer of
      unknown histogenesis. Data from genome-wide surveys for chromosomal aberrations
      in EMPD are limited. OBJECTIVES: To identify chromosomal aberrations that are
      present in EMPD. METHODS: Fifteen cases of EMPD were analysed by comparative
      genomic hybridization (CGH). We used pooled DNA CGH, instead of studying a single
      sample. In addition, immunohistochemistry was performed for detection of androgen
      receptor (AR). RESULTS: The most recurrent change was amplification at
      chromosomes Xcent-q21 and 19, and loss at 10q24-qter. In addition, expression of
      AR, located in chromosome X, was found in six cases. CONCLUSIONS: Results suggest
      that AR may play a role in EMPD tumorigenesis.

PMID- 16086739
TI  - Keloid-derived fibroblasts show increased secretion of factors involved in
      collagen turnover and depend on matrix metalloproteinase for migration.
AB  - BACKGROUND: A keloid is a specific skin lesion that expands beyond the boundaries
      of the original injury as it heals. Histologically, it is characterized by the
      excessive accumulation of collagen. However, the reasons for the expansion and
      the invasive nature of keloids remain unknown. OBJECTIVES: We evaluated collagen
      degradation and migration by cultured keloid fibroblasts based on the assumption
      that these variables were of functional relevance to the expanding and invasive
      nature of keloid lesions. METHODS: Collagen production was investigated by the
      detection of type 1 collagen (procollagen type 1C peptide: P1P). Matrix
      metalloproteinase (MMP)-1 (interstitial collagenase) and MMP-2 (gelatinase-A),
      were investigated as elements of the collagen degradation system. Enzyme
      immunoassays were performed to measure the production of P1P, MMP-1, MMP-2, and
      tissue inhibitor of metalloproteinase (TIMP)-1. To assess the production of MMP-2
      its gelatinolytic activity was measured by zymography using gelatin-containing
      gels. The participation of transforming growth factor-beta1 (TGF-beta1) in the
      production and degradation of collagen was also investigated. Finally, the
      migratory activity of keloid fibroblasts was evaluated using a colony dispersion
      assay. RESULTS: The production of type 1 collagen, MMP-1, MMP-2, and TIMP-1 by
      keloid fibroblasts was 3-fold, 6-fold, 2.4-fold, and 2-fold greater than that of
      normal dermal fibroblasts, respectively. Production of P1P was increased when TGF
      beta1 was added to cultures of keloid fibroblasts, while it was decreased when
      anti-TGF-beta1 antibody was added to the cultures. In contrast, the production of
      MMP-1 was decreased by the addition of TGF-beta1 to cultured keloid fibroblasts,
      while it was increased when anti-TGF-beta1 antibody was added to the cultures.
      The production of MMP-2 increased after treatment with TGF-beta1, but did not
      change significantly when anti-TGF-beta1 antibody was added to the cultures.
      Production of TIMP-1 did not change significantly when either TGF-beta1 or anti
      TGF-beta1 antibody was added to the cultures. Keloid fibroblasts showed a 2.5
      fold increase of migratory activity compared with normal dermal fibroblasts,
      while the migratory activity of these fibroblasts was reduced to the control
      level by treatment with a broad-spectrum MMP inhibitor (GM 6001). CONCLUSIONS:
      Cultured keloid fibroblasts showed increased production of collagen and MMPs, and
      TGF-beta1 played a role in this regulation of production. In addition, increased
      production of MMPs had a role in the high migratory activity of cultured keloid
      fibroblasts.

PMID- 16086740
TI  - Differential expression of nitric oxide synthases in human scalp epidermal and
      hair follicle pigmentary units: implications for regulation of melanogenesis.
AB  - BACKGROUND: Nitric oxide (NO) is a ubiquitous gaseous lipophilic molecule
      generated from the conversion of L-arginine to L-citrulline by the NO synthases
      (NOSs). Ultraviolet radiation (UVR)-induced NO production appears to stimulate
      epidermal melanogenesis. However, given their relative protection from UVR, it is
      unclear whether NO plays a similar role in hair bulb melanocytes. OBJECTIVES: We
      aimed to identify the expression profiles of the NOS isoforms endothelial NOS
      (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) and of phosphorylated eNOS
      and nitrotyrosine within the epidermal and follicular melanin units of normal
      human haired scalp during the hair growth cycle. METHODS: This study employed
      single and double immunohistochemical and immunofluorescence staining techniques
      using haired scalp from 10 healthy individuals (six women and four men). RESULTS:
      Melanocytes in the basal layer of the epidermis expressed eNOS, nNOS and
      nitrotyrosine. By contrast, melanogenically active melanocytes of the anagen hair
      bulb were wholly negative for these markers. However, other follicular
      melanocytes not actively involved in pigment production, including
      undifferentiated melanocytes located in the outer root sheath and melanocytes
      surviving the apoptosis-driven hair follicle (HF) regression during
      catagen/telogen, expressed eNOS, nNOS and nitrotyrosine. While iNOS was only
      weakly expressed in the basal layer of the human epidermis, it was highly
      expressed in keratinocytes of the inner root sheath (IRS), where it colocalized
      with trichohyalin, a differentiation-associated protein of the IRS that requires
      enzyme-catalysed conversion of arginine to citrulline. CONCLUSIONS: The NOS
      isoforms and nitrotyrosine are differentially expressed in different cutaneous
      melanocyte subpopulations. Results of this study suggest a possible role for
      eNOS, nNOS, iNOS and nitrotyrosine in melanocyte biology, particularly with
      respect to melanogenesis and melanocyte survival during HF regression. Another
      example of possible NO involvement in HF biology is the postsynthetic
      modification of trichohyalin in differentiating keratinocytes of the IRS. These
      results suggest that NO may influence several aspects of HF biology.

PMID- 16086741
TI  - Hereditary mucoepithelial dysplasia: clinical, ultrastructural and genetic study
      of eight patients and literature review.
AB  - BACKGROUND: Hereditary mucoepithelial dysplasia is a dominantly inherited
      disease, mainly characterized by chronic mucosal lesions associated with
      keratitis, non-scarring alopecia, keratosis pilaris and perineal intertrigo.
      Since the original report by Witkop, this condition has been considered to be a
      disorder of desmosome/gap junction formation, but there has been no ex vivo
      investigation of these components using genetic and immunolabelling techniques.
      OBJECTIVES: To perform light and immunoelectron microscopic studies, and partial
      genetic analysis on five patients in a family and three sporadic cases and to
      point out similarities of this rare disorder with chronic mucocutaneous
      candidiasis and other follicular keratosis syndromes, i.e. ichthyosis
      follicularis-alopecia-photophobia (IFAP), keratitis-ichthyosis-deafness (KID) and
      Siemens syndromes. METHODS: Biopsies from the involved oral mucosa and armpit
      skin of patient 1 were prepared for standard histopathology, electron microscopy
      and immunocytochemistry. Microsatellite genotyping was performed in three
      affected family members. Direct sequencing after polymerase chain reaction
      amplification of the entire coding region was performed. RESULTS: A 14-year-old
      male had recurrent keratitis, widespread keratosis pilaris, perineal intertrigo,
      hypotrichosis and oral mucosal involvement. A similar phenotype was noted in four
      members of his family and in three sporadic cases. Histological examination of
      oral mucosa and skin samples showed a psoriasiform pattern, dyskeratotic features
      and cytoplasmic vacuoles. Expression of connexins (Cx), desmosomal, adherens
      junction and cytoskeleton proteins (Cx 26, 32 and 43, desmogleins 1 and 2,
      plakoglobin, desmoplakins I-II, plakophilin 1, beta-catenin, E-cadherin,
      keratins, beta-tubulin, vimentin and actin) was normal. Ultrastructural studies
      showed a reduced number of desmosomes. Dyskeratotic cells exhibited internalized
      gap junctions, long filamentous inclusions reactive with antikeratin antibodies,
      and bundles of perinuclear fibres resembling clear tonofilaments. Genetic
      analysis in the studied family excluded the desmosomal cadherins in chromosome
      18q12 as candidate genes. CONCLUSIONS: A diagnosis of hereditary mucoepithelial
      dysplasia should be strongly suggested by the triad of non-scarring alopecia,
      well-demarcated erythema of oral mucosa and psoriasiform perineal rash, after
      exclusion of the clinically related follicular keratosis syndromes. Defective
      expression of cytoskeleton elements and/or a modification of mechanisms
      regulating junction-cytoskeleton assembly may be primarily responsible for
      impaired epithelial cohesion.

PMID- 16086742
TI  - Functional properties of the stratum corneum in patients with diabetes mellitus:
      similarities to senile xerosis.
AB  - BACKGROUND: Although diabetes mellitus is known to induce many pathophysiological
      changes in the skin, none of the earlier studies has focused on the state of the
      stratum corneum (SC) in patients with diabetes. In our previous report on a
      diabetic mouse model, we described a decreased SC hydration state and
      abnormalities in the function of the sebaceous gland together with a normally
      retained barrier function of the SC. OBJECTIVES: To examine the functional
      changes of the SC in patients with diabetes. METHODS: The following values were
      measured in 49 patients with diabetes: fasting plasma glucose (FPG) and
      haemoglobin A1c (HbA1c); skin surface lipid level on the forehead; and high
      frequency conductance (HFC) and transepidermal water loss (TEWL) of the SC of the
      volar forearm and extensor surface of the lower leg. These functions of the SC
      were compared in two pairs of patient groups, i.e. between groups with high and
      low FPG, and between groups with high and low HbA1c. RESULTS: The HFC levels on
      the extensor leg and volar forearm were significantly lower in the group with
      high FPG (FPG > 110 mg dL(-1)) than in the group with low FPG (FPG < 110 mg dL(
      1)), although TEWL values were almost the same in these two groups. The skin
      surface lipids on the forehead were significantly lower in the former than in the
      latter. The HFC did not differ significantly between the group with high HbA1c
      (HbA1c > 5.8%) and the group with low HbA1c (HbA1c < 5.8%), whereas the TEWL of
      the volar forearm was slightly lower in the former than in the latter.
      CONCLUSIONS: These new results as well as our earlier results with diabetic mice
      suggest that patients with diabetes mellitus tend to show a reduced hydration
      state of the SC together with decreased sebaceous gland activity, without any
      impairment of the SC barrier function.

PMID- 16086743
TI  - Circulating CD8+ lymphocytes, white blood cells, and survival in patients with
      mycosis fungoides.
AB  - BACKGROUND: There is a need for reliable, easily measurable laboratory markers
      that may help dermatologists to predict the course of mycosis fungoides (MF) when
      they first evaluate their patients. OBJECTIVES: Our objective was to identify
      clinical, haematological or immunological parameters as predictors of mortality
      in patients with MF. METHODS: We conducted a retrospective study on a prevalent
      cohort of 124 patients with MF hospitalized at IDI-IRCCS, Rome, Italy, from 1983
      to 2001. We calculated the proportion of patients surviving (Kaplan-Meier product
      limit estimates) 5 and 10 years after first hospital admission, and hazard ratios
      (HR) from the Cox proportional hazards model. RESULTS: Patients' survival was
      linked to age and staging (lower survival in older patients and in patients with
      staging IIB-IV). Higher numbers of white blood cells (WBC) and neutrophils, lower
      numbers of CD8+ lymphocytes, low haematocrit and lower levels of albumin were
      significantly associated with a lower survival probability. When simultaneously
      accounting for age and staging, CD8+ [HR = 3.02, 95% confidence interval (CI)
      1.01-9.07 for CD8+ < 250 vs. > or = 600 cells microL(-1)] and WBC (HR = 2.59, 95%
      CI 0.96-6.96 for WBC > or = 9000 vs. < 6000 cells microL(-1)) were associated
      with survival. In addition, we observed an exceedingly high risk of death (HR =
      12.40, 95% CI 3.11-49.43) for patients with a combination of WBC > or = 9000 and
      CD8+ < 600 cells microL(-1) vs. WBC < 9000 and CD8+ > or = 600 cells microL(-1)).
      CONCLUSIONS: The measurement of CD8+ cells and WBC in MF seems to be a promising
      criterion to predict survival, and possibly to support treatment decisions and
      inclusion of patients in randomized controlled trials.

PMID- 16086744
TI  - Thyroid autoimmunity in chronic urticaria.
AB  - BACKGROUND: Chronic urticaria (CU) is an autoimmune process in some patients. An
      association between CU and autoimmune thyroid disease has also previously been
      proposed. Our group has identified functionally significant histamine-releasing
      autoantibodies in one subset of CU patients (subset 1), predicted by positive
      autologous intradermal serum tests and positive histamine release from donor
      basophil leucocytes in vitro. Sera from a second subset of patients (subset 2),
      all of whom had positive autologous intradermal serum tests, failed to release
      histamine from donor basophils. A final disease subset (subset 3) has no
      identifiable skin reactivity (negative autologous serum skin test) or in vitro
      histamine releasing activity. OBJECTIVES: In order to examine further the
      possible relationships between thyroid autoimmunity, thyroid dysfunction and CU,
      we have examined thyroid autoantibodies and thyroid-stimulating hormone (TSH)
      levels (an indirect measure of thyroid dysfunction) in the three CU subsets.
      PATIENTS/METHODS: We studied 182 patients (69% female), of whom 90 had a positive
      autologous intradermal serum test. RESULTS: Eighteen skin test-positive and four
      skin test-negative patients had thyroid microsomal antibodies (TMA). TSH outside
      the normal range was found in 13 skin test-positive and one skin test-negative
      patient. These findings represent clustering of TMA positivity [risk ratio (RR)
      4.06, 95% confidence interval (CI) 1.56-10.6] and of abnormal thyroid function
      (RR 15.5, CI 2.07-11.6) among the skin test-positive patients. However, in the
      overall study group an elevated TSH was present in seven patients (3.8%, CI 1.6
      7.8) comparable to the 5% expected prevalence in the community. Thyroglobulin
      antibodies (TGA) were present in two of 182 patients. CONCLUSIONS: There were
      significant differences between skin test-positive and skin test-negative
      patients with regard to autoimmune thyroid disease. Evidence for autoimmune
      thyroid disease and abnormal thyroid function was largely found among the skin
      test-positive patients, supporting the theory of an autoimmune aetiology in this
      group.

PMID- 16086745
TI  - A systematic review of placebo-controlled randomized clinical trials of
      treatments used in oral lichen planus.
AB  - BACKGROUND: Oral lichen planus (OLP) is one of the commoner conditions seen in
      oral medicine clinics. Current treatments are palliative rather than curative.
      Numerous treatments have been tried but many have not been evaluated in
      randomized controlled trials (RCTs). OBJECTIVES: To review the effectiveness and
      safety of any therapy compared with placebo for the treatment of symptomatic OLP.
      METHODS: A systematic review of 11 RCTs, totalling 223 patients was done. The
      main outcome measures used were improvement of signs (erythema, reticulation,
      ulceration) and symptoms (pain, discomfort) usually after 8 weeks of therapy.
      RESULTS: Eleven interventions were grouped into four therapeutic classes (topical
      ciclosporins, topical or systemic retinoids, topical steroids and phototherapy)
      for comparison. No therapy was replicated exactly. Trials recording the same
      outcomes in each therapeutic class were pooled. The largest number of pooled
      trials was four. Small odds ratios with very wide confidence intervals indicating
      statistically significant but imprecisely known treatment benefits were seen in
      all but one trial. Only systemic agents were associated with treatment
      toxicities; all other side-effects were mild and mainly local. CONCLUSIONS: The
      results are tempered by the small study sizes, lack of replication, lack of
      standardized outcome measures and the very high likelihood of publication bias.
      Therefore this review provides only circumstantial evidence for the superiority
      of the assessed interventions over placebo for the palliation of symptomatic OLP.
      There is a need for larger placebo-controlled RCTs with carefully selected and
      standardized outcome measures.

PMID- 16086746
TI  - The double-RNA-specific adenosine deaminase (DSRAD) gene in dyschromatosis
      symmetrica hereditaria patients: two novel mutations and one previously
      described.
AB  - BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH, MIM 127400) is an
      autosomal dominant pigmentary genodermatosis. Pathogenic mutations in the double
      RNA-specific adenosine deaminase (DSRAD) gene encoding an RNA editing enzyme have
      recently been identified. OBJECTIVES: To identify gene mutations of DSRAD in
      Chinese patients with DSH. METHODS: Three unrelated Chinese patients with DSH
      were subjected to mutation detection in DSRAD. Two had family histories of DSH.
      All the coding exons and their flanking sequences were amplified and sequenced.
      RESULTS: All three patients had heterozygous mutations including one non-sense,
      one frameshift and one missense mutation in DSRAD. CONCLUSIONS: Two novel
      mutations, c.3169delC (p.L1057fs) and c.3247C-->T (p.R1083C), and one recurrent
      mutation c.1420C-->T (p.R474X), were found in this series of Chinese patients
      with DSH.

PMID- 16086747
TI  - Psoriasis in Norway as observed in a population-based Norwegian twin panel.
AB  - BACKGROUND: Psoriasis is a chronic T-cell-mediated immunological skin disease.
      The occurrence of the disease appears to differ with geography and ethnicity.
      There is a need for epidemiological data obtained from defined population-based
      studies, and the sex-specific differences observed in the natural history of the
      disease require more attention. OBJECTIVES: To describe the occurrence and risk
      of psoriasis in Norway by age and sex. PATIENTS/METHODS: A population-based
      health survey was conducted in 1998 in Norwegian twins aged 19-31 years. The
      present study is based upon the self-reported history of psoriasis among the 8045
      questionnaire responders. RESULTS: Altogether, 334 (4.2%) reported a positive
      history of psoriasis. There were no sex differences in the overall prevalence
      rates, but significantly higher point-prevalences emerged in females in the
      teenage-year intervals. A fairly linear increase in incidence rates by every 4
      year age-interval peaked at a lower age in females. The mean age at onset was
      also significantly lower in females (14.8 years) than in males (17.3 years). The
      absolute risk of developing psoriasis appeared higher for females across the
      entire age range. However, by the age of 31 the cumulative risks were similar in
      females and males (0.056 and 0.053, respectively). CONCLUSIONS: In this
      historical cohort of Norwegian twins, we find a high prevalence of psoriasis in
      congruence with previously reported data among whites in north-western Europe. We
      have found sex-specific characteristics in point-prevalences and incidence rates
      which may contribute to the understanding of the earlier age at onset of the
      disease in females.

PMID- 16086748
TI  - A comparison between criteria for diagnosing atopic eczema in infants.
AB  - BACKGROUND: Epidemiological studies have shown different estimates of the
      frequency of atopic eczema (AE) in children. This may be explained by several
      factors including variations in the definition of AE, study design, age of study
      group, and the possibility of a changed perception of atopic diseases. The role
      of IgE sensitization in AE is a matter of debate. OBJECTIVES: To determine the
      prevalence and cumulative incidence of AE in a group of unselected infants
      followed prospectively from birth to 18 months of age using different diagnostic
      criteria; to evaluate the agreement between criteria; and to describe the
      association between atopic heredity and postnatal sensitization, respectively,
      and the development of AE according to the different diagnostic criteria.
      METHODS: During a 1-year period a consecutive series of 1095 newborns and their
      parents were approached at the maternity ward at the Odense University Hospital,
      Denmark and a cohort of 562 newborns was established. Infants were examined and
      followed prospectively from birth and at 3, 6, 9, 12 and 18 months of age. AE was
      diagnosed using four different criteria, the Hanifin and Rajka criteria, the
      Schultz-Larsen criteria, the Danish Allergy Research Centre (DARC) criteria
      developed for this study and doctor-diagnosed visible eczema with typical
      morphology and atopic distribution. Additionally, the U.K. diagnostic criteria
      based on a questionnaire were used at 1 year of age. Agreement between the four
      criteria was analysed at each time point and over time, and agreement between the
      four criteria and the U.K. questionnaire criteria was analysed. RESULTS: The
      cumulative 1-year prevalence of AE using the Hanifin and Rajka criteria was 9.8%
      (95% confidence interval, CI 7-13%), for the Schultz-Larsen criteria it was 7.5%
      (95% CI 5-10%), for the DARC criteria 8.2% (95% CI 6-11%), for visible eczema
      12.2% (95% CI 9-16%) and for the U.K. criteria 7.5% (95% CI 5-10%). The pairwise
      agreement between criteria showed good agreement, with rates varying between 93%
      and 97% and kappa scores between 0.6 and 0.8. Agreement analysis of diagnoses
      between the four criteria demonstrated that cumulative incidences showed better
      agreement than point prevalence values. CONCLUSIONS: Agreement between different
      criteria for diagnosing AE was acceptable, but the mild cases constituted a
      diagnostic problem, although they were in the minority. Repeated examinations
      gave better agreement between diagnostic criteria than just one examination.
      Atopic heredity was less predictive for AE than sensitization to common food and
      inhalant allergens in early childhood.

PMID- 16086749
TI  - Serum antidiuretic hormone is elevated in relation to the increase in average
      total body transepidermal water loss in severe atopic dermatitis.
AB  - BACKGROUND: While elevation of antidiuretic hormone (ADH) (arginine vasopressin)
      levels in the serum has been reported in severe atopic dermatitis (AD), the cause
      is as yet unexplained. On the other hand, transepidermal water loss (TEWL) is
      known to increase in the damaged skin due to AD. OBJECTIVES: As ADH increases as
      a result of dehydration of the body, this study examined whether the high ADH
      level in severe AD is a reaction to the increased water loss through the entire
      body skin surface area. METHODS: Forty-eight patients of different ages and with
      various degrees of AD along with six age- and sex-matched control persons were
      the study subjects. Using a quick responsive evaporimeter, an average total body
      TEWL (ATEWL) value was obtained for each subject. Laboratory tests including ADH,
      serum lactate dehydrogenase (LDH) and peripheral blood eosinophil count (EOS)
      were also performed. Clinical severity grading was made globally. The relevancy
      of this grading was empirically demonstrated by its statistically significant
      relation to LDH and EOS which are commonly known as appropriate gauges for AD
      severity. Results ATEWL was observed to be significantly greater in patients with
      AD of at least moderate severity than in normal controls, and ADH was
      significantly greater in patients with severe and very severe AD. Both ATEWL and
      ADH showed a significant relation to AD severity. Finally, a significant
      correlation was found between ADH and ATEWL. CONCLUSIONS: It is possible that
      elevated ADH is at least in part a reaction to increased ATEWL.

PMID- 16086750
TI  - Analysis of para-phenylenediamine allergic patients in relation to strength of
      patch test reaction.
AB  - BACKGROUND: Despite having a positive patch test reaction to para
      phenylenediamine (PPD), some patients continue to dye their hair, while others
      are forced to give up or abandon this practice. This difference in patient
      behaviour could be due to the degree of sensitization. OBJECTIVES: To establish
      whether the ability to continue dyeing hair in PPD allergic patients is related
      to the strength of patch test reaction. To note differences in other clinical
      features in relation to the strength of patch test reaction. METHODS: We analysed
      retrospectively the patch test records of 400 sequential PPD-positive patients
      for the strength of patch test reaction (+, ++, +++) and different clinical
      features. Data were analysed using Cochran-Mantel-Haenszel chi2 tests. RESULTS:
      There was a strong linear relationship between the strength of patch test
      reaction and continuation with hair dyeing. Patients were more likely to report a
      history of hair dye reaction with increasing strength of patch test reaction.
      There was no difference in strength of patch test reaction in relation to age,
      site of rash, occupation (hairdressing) or history of atopic eczema. Overall
      concomitant reactivity with related aromatic amine allergens (benzocaine, N
      isopropyl-N-phenyl-para-phenylenediamine, para-aminobenzoic acid) was infrequent.
      CONCLUSIONS: Patients with stronger patch test reactions (++, +++) are more
      likely to have a clear history of reacting to hair dye and are less likely to
      still be dyeing their hair.

PMID- 16086751
TI  - The usefulness of clonality for the detection of cases clinically and/or
      histopathologically not recognized as cutaneous T-cell lymphoma.
AB  - BACKGROUND: The determination of clonality has proven to be a useful adjunct to
      the diagnosis of cutaneous lymphocytic infiltrates. It is considered particularly
      helpful for the distinction of mycosis fungoides (MF) and inflammatory
      dermatoses. OBJECTIVES: To verify the sensitivity of the polymerase chain
      reaction (PCR)-heteroduplex analysis of T-cell receptor gamma-chain gene
      (TCRgamma) rearrangements in patients with MF and to establish whether a
      clinicopathological re-evaluation of lesions previously unclassified or
      considered to be non-neoplastic entities but found to be monoclonal allowed the
      recognition of additional cases of MF. METHODS: Included in the study were 116
      patients, seen at our Institute from April 2002 to September 2003 and tested for
      TCRgamma rearrangements. Thirty-six patients were affected by clinically and
      histopathologically proven MF, while the remaining 80 cases had not been
      classified or had been classified as non-neoplastic entities. The sensitivity of
      the molecular analysis was determined on the basis of the results obtained in the
      36 patients with MF. The 29 cases of the second series of patients found to be
      monoclonal were clinically and histopathologically re-evaluated. RESULTS: Clonal
      rearrangements were found in 87.5% of patients with plaque stage MF and in 20% of
      those with patch stage MF. The clinicopathological re-evaluation allowed us to
      reclassify 15 of 29 monoclonal cases of the second series of patients as MF.
      CONCLUSIONS: The study showed that the PCR-heteroduplex technique can determine a
      high percentage of monoclonality only in plaque stage MF. However, in spite of
      the low sensitivity of the method, several cases previously unrecognized could be
      reclassified as MF when their clinical and histopathological features were re
      evaluated taking into account the clonality of the lymphocytic infiltrate.

PMID- 16086752
TI  - The development of a preference-based measure of health in children with atopic
      dermatitis.
AB  - BACKGROUND: Outcomes of health care interventions can be measured in many
      different ways, but there has been growing interest in the role that quality
      adjusted life-years (QALYs) can play in informing priorities in health care.
      While existing generic preference-based measures can be used to obtain QALYs,
      these measures may often be inappropriate for some conditions such as atopic
      dermatitis (AD). These measures are also usually developed for adults and may not
      capture the domains pertinent to children. OBJECTIVES: To develop a preference
      based quality-of-life measure for use in children with AD. METHODS: Items
      generated from interviews conducted with parents of children with AD were used to
      form a health state classification system that gives 16 unique health states. One
      hundred and fifty members of the general population were interviewed to derive
      preference weights for these states, following the methods used in the valuation
      of the Health Utilities Index 2 (HUI 2). Each person valued 10 health states
      using the standard gamble technique. The primary analysis was the estimation of
      mean health state values for each of the 16 states. RESULTS: Mean values across
      the 16 health states range from 0.36 (SD = 0.36) for the worst state to 0.84 (SD
      = 0.19) on a scale from zero to one, where zero is for health states thought to
      be as bad as being dead and one is for perfect health. There was some support for
      the validity of the values from the fact that the values were logically
      consistent with the ordering of the health state classification system.
      CONCLUSIONS: These results show the perceived importance of the defined health
      states of childhood AD to the general population. The resultant health state
      classification and values can be used to calculate QALYs for use in assessing the
      cost-effectiveness of interventions for children with AD.

PMID- 16086753
TI  - Sunscreens and melanoma: the future looks bright.
AB  - BACKGROUND: Meta-analyses of observational case-control studies have demonstrated
      no association between sunscreen use and the development of malignant melanoma.
      OBJECTIVES: To examine whether this observation is to be expected given the
      period during which the case-control studies were conducted, the sunscreens
      prevalent at that time, and how sunscreen is used and applied in practice. To
      predict whether modern sunscreens are likely to be effective as a preventative
      agent in melanoma. METHODS: The protection against solar ultraviolet radiation
      delivered by sunscreens available prior to the early 1990s (when the data used in
      most published case-control studies were collected) was estimated by combining
      their absorption properties with the amount applied in a way reflecting common
      usage. Similar estimates were made for the protection offered by modern
      sunscreens. RESULTS: It is not surprising that case-control studies have failed
      to find any association between sunscreen use and the risk of melanoma when
      consideration is given to the sunscreens in common usage at the time and the way
      in which sunscreen is applied in practice. Modern high Sun Protection Factor,
      broad-spectrum sunscreens, on the other hand, can be expected to be an effective
      measure in helping to prevent melanoma compared with sunscreens typical of those
      used 10-20 years ago. CONCLUSIONS: It is reasonable to suppose that the
      improvement in performance of modern sunscreens will lead to a worthwhile benefit
      as a preventative agent against melanoma, although these benefits may not be seen
      for several decades.

PMID- 16086755
TI  - Topical pimecrolimus in the treatment of genital lichen planus: a prospective
      case series.
AB  - BACKGROUND: A potent topical steroid is the conventional therapy for genital
      lichen planus (GLP). Side-effects or steroid resistance can be encountered and
      second-line therapy such as topical tacrolimus may be required. In our experience
      tacrolimus may be poorly tolerated in genital skin because of a burning
      sensation. In addition, there is impairment of Langerhans cell function, raising
      concerns about its long-term use. These adverse effects may not be as marked with
      pimecrolimus. To our knowledge, pimecrolimus has not been used in the treatment
      of GLP. OBJECTIVES: To assess the efficacy and tolerability of topical
      pimecrolimus in the treatment of GLP. METHODS: Eleven women with GLP were
      recruited: 10 had erosive vulval disease and one had classical lichen planus of
      perianal skin. Ten patients had poor disease control, and despite using topical
      steroids appropriately, two of these also had steroid-related side-effects in
      adjacent unaffected skin. The eleventh patient had adequate disease control but
      marked steroid atrophy. Topical pimecrolimus 1% cream (Elidel cream; Novartis,
      Camberley, U.K.) was applied twice daily to affected areas. Patients were
      followed up between 4 and 6 weeks later. They remain under regular review and at
      the time of writing mean follow-up is 5.2 months (range 2-10). RESULTS: Nine
      patients (82%) tolerated pimecrolimus, including three patients previously
      intolerant of tacrolimus. These nine patients showed a clinical response at 4-6
      weeks: two showed a complete response with no residual disease activity visible
      and seven had a partial response. With longer follow-up, six (55%) of the women
      had a complete response and three (27%) were considered to have a partial
      response. Eight patients noted symptomatic improvement and one felt that her
      symptoms were the same as with steroid use. Two patients (18%) with erosive
      lichen planus were unable to tolerate pimecrolimus due to local irritation.
      CONCLUSIONS: We have found that topical pimecrolimus 1% cream is an effective
      treatment for GLP. Local irritation can limit its use, but it may be better
      tolerated than topical tacrolimus: three of our complete responders had
      previously been intolerant of tacrolimus. Topical pimecrolimus may be a valuable
      second-line treatment for patients with steroid-related side-effects or steroid
      resistant GLP.

PMID- 16086754
TI  - Role of antiretroviral therapies in mucocutaneous manifestations in HIV-infected
      children over a period of two decades.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection causes a severe cellular
      immunodeficiency, which results in a greater susceptibility to infectious,
      inflammatory and malignant conditions. Among these, pathologies of the skin seem
      to be those most frequently observed in HIV+ patients. However, there are few
      reports on how antiretroviral therapy affects skin disorders in HIV-infected
      children. OBJECTIVE: To study the incidence and prevalence of skin disorders in a
      cohort of HIV-infected children, in relation to the antiviral therapy
      [nontreated, monotherapy, combined therapy and highly active antiretroviral
      therapy (HAART)] received, and their impact on immunological and virological
      markers. The treatments were those available in different calendar periods in the
      history of antiviral treatment. MATERIALS AND METHODS: A retrospective,
      observational study in a cohort of 210 HIV-infected children was carried out.
      These children were followed up every 3 months throughout 22 years. The viral
      load (HIV RNA copies mL(-1)) was quantified using reverse transcriptase
      polymerase chain reaction and the viral phenotype of HIV-1 isolates was
      determined by in vitro culture. T-lymphocyte subsets in peripheral blood were
      quantified by flow cytometry. RESULTS: Mucocutaneous manifestations were
      diagnosed in 17% of the untreated infected children. Of the treated children in
      different treatment periods, 22% in the monotherapy period, 25% in the combined
      therapy period but only 10% on HAART had some type of mucocutaneous
      manifestation, concordant with a higher number of CD4+ T cells, a lower viral
      load and less cytopathic virus in the last group. Mucocutaneous manifestations of
      infectious aetiology were most frequently observed; they were detected in 13% of
      the children during the first calendar period (untreated children), 16% during
      the second and third periods (monotherapy and combined therapy) and only 5% in
      the last period (HAART). Interestingly, syncytium-inducing virus was present in
      69% of all children with mucocutaneous manifestations of infectious aetiology.
      CONCLUSION: Only in the last calendar period (HAART) was a significant decrease
      observed in the prevalence of mucocutaneous manifestations with HIV infection
      associated with an increase in CD4+ T cells. In addition, we found a strong
      association between children who had mucocutaneous manifestations with an
      infectious aetiology and a more cytopathic (X4/SI) viral phenotype.

PMID- 16086756
TI  - Treatment of acne with topical antibiotics: lessons from clinical studies.
AB  - BACKGROUND: Over the past 20 years, major concerns have been repeatedly expressed
      over antibiotic-resistant acne in Europe and in the U.S.A. However, the clinical
      significance of these resistance patterns is poorly defined so that topical
      antibiotics remain one of the cornerstones of acne management. OBJECTIVES: To
      determine whether we are facing decreased efficacy of topical formulations of
      erythromycin and clindamycin in clinical trials of therapeutic interventions for
      acne. METHODS: To review systematically the results of the clinical trials
      investigating topical formulations of erythromycin and clindamycin for the
      treatment of inflammatory acne and to establish whether or not there is a
      decrease in the efficacy of these topical antibiotic formulations since their
      widespread introduction in the mid 1970s. RESULTS: Of the 50 eligible controlled
      trials identified using a systematic electronic database search strategy, 45
      (90%) incorporated a lesion count, making comparison across trials possible.
      Analysis of clinical studies investigating the effect of topical erythromycin in
      acne patients indicates a significant decrease in the effect of this antibiotic
      on inflammatory and noninflammatory lesion count over time (r = -2.140, P = 0.001
      and r = -2.032, P = 0.001, respectively). Efficacy of topical clindamycin
      remained stable during the study period. CONCLUSIONS: There is a gradual decrease
      in the efficacy of topical erythromycin in clinical trials of therapeutic
      intervention for acne, which is probably related to the development of antibiotic
      resistant propionibacteria.

PMID- 16086757
TI  - Cutaneous side-effects of transdermal iontophoresis with and without surfactant
      pretreatment: a single-blinded, randomized controlled trial.
AB  - BACKGROUND: Iontophoresis, a method that facilitates drug transport across skin
      by an external electrical field, offers the possibility for long-term transdermal
      delivery of compounds in a well-controlled manner. In general, the literature
      supports the contention that iontophoresis is a safe procedure. However, there
      are important medical issues concerning the epidermal and dermal effects of
      iontophoresis that have not been extensively investigated. Specific and strictly
      controlled studies on the dermal effect of iontophoresis are scarce. OBJECTIVES:
      The aim of this study was to investigate the cutaneous side-effects of
      transdermal iontophoresis application in healthy human volunteers. METHODS: This
      was a single-blinded, randomized and parallel design study. In one group (n=12)
      subjects were treated nonocclusively with a surfactant formulation followed by
      iontophoresis (3-h application at a current density of 250 microA cm(-2)). In
      another group (n=12) iontophoresis alone was performed. No drug was included in
      these studies. The corresponding passive treatments served as controls.
      Noninvasive methods including sensation record, transepidermal water loss (TEWL),
      skin colour and the visual scoring were used to assess cutaneous effects.
      RESULTS: Tingling and itching were commonly experienced in the first 30 min of
      the current application. Iontophoresis in combination with the pretreatment
      induced significant increases in TEWL values and in skin redness, and resulted in
      slight to mild erythema and oedema compared with the control. Compared with the
      iontophoresis alone, the presence of surfactant pretreatment caused slightly more
      skin irritation (erythema and oedema) but did not further disturb the skin
      barrier function. CONCLUSIONS: The transdermal iontophoresis challenges the skin
      barrier function and induces transient mild skin irritation, but does not cause
      any permanent damage to the skin when applied for 3 h at a current density of
      0.25 mA cm(-2).

PMID- 16086758
TI  - Enzyme-linked immunosorbent assay for detection of peptide-specific human
      antidesmoplakin autoantibodies.
AB  - BACKGROUND: Autoantibodies directed against desmoplakin (Dp) I and II have
      recently been characterized in a subset of patients with severe erythema
      multiforme (EM), a recurrent inflammatory skin disease with a broad spectrum of
      clinical manifestations. These autoantibodies recognize a peptide epitope
      localized within the extreme end of the carboxy terminal domain of Dp responsible
      for the assembly of keratin filaments to the desmosomal plaque. Using dot blot
      analysis with overlapping synthetic peptides, the binding epitope YSYSYS has been
      identified. OBJECTIVES: To establish an enzyme-linked immunosorbent assay (ELISA)
      for detection of peptide-specific anti-Dp autoantibodies in sera of patients with
      EM. METHODS: A synthetic peptide containing the respective amino acid sequence
      was used as matrix for ELISA plates. Serum samples from patients with known EM
      and peptide-specific anti-Dp autoantibodies verified by immunoblotting,
      immunoprecipitation and epitope mapping were used. RESULTS: Establishing an index
      value of 42.0, 25 of 25 serum samples from five patients with peptide-specific
      anti-Dp autoantibodies were positive in the ELISA. From control sera, none of 31
      bullous disease sera and only one (1.2%) of 83 normal human sera were positive.
      CONCLUSIONS: These data show that the ELISA presented in this study represents a
      sensitive and highly specific tool for the detection of peptide-specific anti-Dp
      autoantibodies in patients with EM.

PMID- 16086759
TI  - Adverse cutaneous reactions to anakinra in patients with rheumatoid arthritis:
      clinicopathological study of five patients.
AB  - BACKGROUND: Anakinra, a recombinant human form of interleukin-1 receptor
      antagonist, is used to treat patients with active rheumatoid arthritis (RA).
      OBJECTIVES: To report five patients with cutaneous adverse drug reactions due to
      anakinra and to evaluate the histopathological and immunohistochemical findings
      with the aim of understanding the possible mechanisms involved. METHODS: Five
      patients of a series of 10 patients with RA undergoing treatment with anakinra in
      a clinical trial presented inflammatory lesions at the anakinra injection sites.
      In each case, clinical features were recorded and skin biopsy specimens were
      obtained. In one patient sequential biopsy specimens were obtained from skin
      lesions at different stages of development. Tissue sections of the biopsy
      specimens were stained with haematoxylin and eosin and May-Grunwald-Giemsa, and
      were immunoreacted with antibodies to leucocyte common antigen, CD68, CD3,
      CD45RO, CD20 and CD45RA. RESULTS: The onset of reaction was within the first
      month of treatment and appeared as well-defined erythema and oedema involving the
      injection sites. In two patients the treatment had to be discontinued because of
      the skin reaction, and in one patient it was associated with systemic
      involvement. All biopsy specimens exhibited marked dermal oedema and a lichenoid
      dermal infiltrate composed mainly of lymphomononuclear cells with prominent
      populations of eosinophils and large CD68+ dermal macrophages and an increase in
      the number of mast cells, which were spindle shaped in a significant proportion.
      CONCLUSIONS: Cutaneous toxicity is a frequent, usually well-tolerated
      complication of treatment with anakinra in patients with RA, although in some
      cases it can be associated with systemic involvement. The most relevant
      histopathological findings include dermal oedema and a lichenoid, perivascular
      and periadnexal predominantly lymphomononuclear infiltrate, with many eosinophils
      and the presence of enlarged CD68+ macrophages. These findings resemble those
      seen in skin reactions in patients receiving chemotherapy and colony-stimulating
      factors. We also found an increase in mast cell numbers that could be a specific
      effect of anakinra.

PMID- 16086760
TI  - Annual incidence and mortality of bullous pemphigoid in the Grampian Region of
      North-east Scotland.
AB  - BACKGROUND: Data on the annual incidence of bullous pemphigoid (BP) in the U.K.
      are scarce. OBJECTIVES: To estimate the annual incidence of BP in Grampian Region
      (North-east Scotland) and to assess the causes of mortality in this cohort of
      patients. METHODS: Details were obtained of all patients with a diagnosis of BP
      recorded in the database of the Pathology Department, Aberdeen Royal Infirmary
      between January 1991 and December 2001. Community Health Index population data
      were obtained from the Grampian Health Board and the annual incidence and age-
      and sex-specific incidence were calculated. Mortality data were obtained from the
      Patient Administration System and causes of death obtained from the Office of the
      Registrar for Births and Deaths for Scotland. RESULTS: Eighty-three patients met
      criteria for diagnosis of BP. The annual incidence of BP in Grampian region was
      estimated to be 14 cases per million per year. There was a clear and marked rise
      in the incidence in patients over the age of 80 years. Forty-eight per cent of
      patients with BP died within 2 years of diagnosis. The all-cause age-standardized
      mortality ratio was 576%. When compared with cause-specific mortality in the
      Grampian population over 60 years of age, respiratory disease accounted for a
      higher than expected number of deaths in our cohort of patients with BP (odds
      ratio 5.3, 95% confidence interval 3.0-9.4). CONCLUSIONS: North-east Scotland
      appears to have a relatively high incidence of BP when compared with incidence
      rates in continental Europe. The mortality rate in patients with BP is
      considerable, especially within the first 2 years of diagnosis.

PMID- 16086761
TI  - The first case of cutaneous mucormycosis caused by Rhizopus azygosporus.
AB  - A rapidly enlarging leg ulcer appeared in a 54-year-old woman with systemic lupus
      erythematosus receiving aggressive immunosuppressive therapy. Skin biopsy
      revealed proliferation of hyphae in the midst of a neutrophilic abscess. Culture
      yielded Rhizopus azygosporus. As no organ involvement was detected by thorough
      examination, the patient was diagnosed as having primary cutaneous mucormycosis.
      Although intravenous amphotericin B therapy seemed to be very effective, it had
      to be discontinued due to nephrotoxicity. She unfortunately died of subsequent
      disseminated fungal infection and cerebral infarction in which the primary cause
      could not be determined. Minimum inhibitory concentrations of several antifungal
      drugs to the isolate were examined and amphotericin B proved to be the only agent
      that may potentially reach the effective plasma concentration. This is the first
      case report of cutaneous mucormycosis caused by R. azygosporus.

PMID- 16086762
TI  - Elastosis perforans serpiginosa-like pseudoxanthoma elasticum in a child with
      severe Moya Moya disease.
AB  - A 2-year-old girl with Moya Moya disease who had relapsing cerebrovascular
      strokes presented with loose skin folds, 'chicken' skin appearance and
      perforating elastosis serpiginosa-like lesions in the genitocrural region.
      Histologically, calcified material perforating the epidermis and adjacent short
      curled and mineralized elastic fibres suggested a variant of pseudoxanthoma
      elasticum (PXE). As PXE is known to be caused by various mutations in the
      transmembrane transporter ABCC6 gene, we hypothesized that a novel ABCC6 mutation
      may underlie this unique combination of PXE and elastopathic vascular damage.
      Therefore, the complete ABCC6 coding region of the patient and her parents was
      screened for genetic alterations. No bona fide disease-causing mutation of ABCC6
      could be found in the child and in her parents. However, two novel allelic amino
      acid substitutions (Arg1273Lys and Glu1293Lys; exon 27) were found in the girl
      and her father, localized in close proximity to the region that codes for the
      functionally critical second nucleotide-binding fold of ABCC6. Although a causal
      involvement of these amino acid substitutions could not be proven based on this
      study, both heterozygote substitutions may possibly have interacted with other
      undetected recessive maternal ABCC6 changes in the child. To the best of our
      knowledge, this is the first report of an association between early-onset PXE and
      severe Moya Moya syndrome possibly related to ABCC6 changes.

PMID- 16086763
TI  - Bullous delayed pressure urticaria: pathogenic role for eosinophilic
      granulocytes?
AB  - Bullous delayed pressure urticaria (DPU) is a rare variant of DPU. Treatment of
      DPU is difficult and the underlying pathogenic mechanism of DPU remains elusive.
      We report a 72-year-old man with DPU and associated chronic urticaria as well as
      delayed urticarial dermographism. Pressure challenge gave rise to a deep weal
      covered by multiple vesicles and bullae after 24 h. Histological examination of a
      skin biopsy specimen obtained 24 h after pressure challenge demonstrated
      intraepidermal bullae filled with eosinophils accompanied by a dense,
      predominantly eosinophilic infiltrate in the dermis. Whereas the numbers and
      morphology of mast cells were unaltered, the extracellular deposition of
      eosinophil cationic protein revealed evidence for eosinophil activation.
      Concomitantly, both CD4+ and CD8+ T lymphocytes were present in the infiltrate
      and expressed interleukin 5. As bullous DPU may represent the maximal variant of
      DPU, the investigation of the cellular infiltrate and the chemokines/cytokines
      released may reveal potential pathogenic mechanisms. A possible effector role of
      eosinophilic granulocytes, T-cell subsets and mast cells is discussed.

PMID- 16086764
TI  - Cold urticaria; disease course and outcome--an investigation of 85 patients
      before and after therapy.

PMID- 16086765
TI  - Docetaxel-induced recall dermatitis on previous laser treatment sites.

PMID- 16086766
TI  - Cyclophosphamide-dexamethasone pulsed therapy for treatment of recalcitrant
      necrobiotic xanthogranuloma with paraproteinemia and ocular involvement.

PMID- 16086767
TI  - Successful treatment of recalcitrant acrodermatitis continua of Hallopeau with
      adalimumab and acitretin.

PMID- 16086768
TI  - Inpatient compliance of topical applications.

PMID- 16086769
TI  - Rapid control of therapy-refractory pemphigus vulgaris by treatment with the
      tumour necrosis factor-alpha inhibitor infliximab.

PMID- 16086770
TI  - Long-standing remission of recalcitrant juvenile pemphigus vulgaris after
      adjuvant therapy with rituximab.

PMID- 16086771
TI  - Generalized cowpox infection probably transmitted from a rat.

PMID- 16086772
TI  - More skin cancer detected from nonurgent referrals.

PMID- 16086773
TI  - High local interleukin 5 production in granuloma faciale (eosinophilicum): role
      of clonally expanded skin-specific CD4+ cells.

PMID- 16086774
TI  - Vulval adenosis associated with toxic epidermal necrolysis.

PMID- 16086776
TI  - Who should treat patients with primary melanoma?

PMID- 16086777
TI  - The place of botulinum toxin type A in the treatment of focal hyperhidrosis.

PMID- 16086778
TI  - A new type of erythrokeratoderma, or KLICK syndrome?

PMID- 16086781
TI  - Evidence for a role of type I interferons in the pathogenesis of dermatomyositis.

PMID- 16086784
TI  - Radioisotopic reflections.
AB  - The transfusion of radiolabeled red cells and platelets (PLTs) allows for the
      accurate determination of in vivo recovery and survival after subjecting the
      cells to an experimental collection, processing, or storage system. The
      techniques utilized in these protocols have undergone refinement over the past
      several decades, and these improvements have reduced interlaboratory variability
      and improved the accuracy of the techniques. At present, the field is evolving
      toward new applications of these radiolabeling techniques, including, for PLTs,
      the use of freshly collected autologous PLTs as the standard-setting PLTs against
      which the "test" PLTs can be compared. The contribution of the National Blood
      Foundation in supporting research in these fields is acknowledged with
      appreciation because its efforts have helped advance not only the science
      involved but also the scientists engaged in this research.

PMID- 16086785
TI  - Deleterious clinical effects of transfusion immunomodulation: proven beyond a
      reasonable doubt.

PMID- 16086786
TI  - The impact of the National Blood Foundation.

PMID- 16086787
TI  - Control of immune responses induced by the transfer of allogeneic white blood
      cells during transfusion.

PMID- 16086788
TI  - Transforming growth factor-beta1, Th1 responses, and autoimmune liver disease.
AB  - Transforming growth factor-beta1 (TGF-beta1) is released during the storage of
      blood components, particularly platelet concentrates, and transfusion recipients
      are exposed to high levels of TGF-beta1. Because TGF-beta1 is one of the most
      potent immunosuppressive cytokines known, understanding the immunobiologic
      functions of TGF-beta1 may be relevant for understanding the immunobiologic
      effects of transfusion. Our laboratory studies the biologic effects of TGF-beta1
      in the immune system. Mice deficient in TGF-beta1 spontaneously develop
      autoimmunity, confirming the important role of this cytokinean an immune
      regulator. A few years ago, my laboratory made the observation that genetic
      background strongly affects the phenotype of TGF-beta1-/- mice. TGF-beta1-/- mice
      on the BALB/c background rapidly develop an aggressive T-cell-mediated hepatitis,
      whereas TGF-beta1-/- mice on the 129/CF-1 background do not. In this review, I
      summarize findings published or in press from our laboratory on disease
      pathogenesis in TGF-beta1-/- mice and then discuss some of the exciting (as-yet
      unpublished) directions our laboratory is currently taking.

PMID- 16086789
TI  - Studies of thrombotic thrombocytopenic purpura: the role of the AABB Research
      Foundation grant.

PMID- 16086790
TI  - From an early National Blood Foundation award to our ongoing studies in fetal and
      neonatal alloimmune thrombocytopenia.

PMID- 16086791
TI  - The importance of National Blood Foundation funding.
AB  - The research award that I received from the National Blood Foundation (NBF) was
      very important to me early in my career for several reasons. The funding itself
      was important for performing the experiments proposed, and the data obtained have
      played a role in much of the research that has been performed in my laboratory
      since that time. Also, receiving the award was a very important vote of
      confidence by the grant review committee at an early time in my career as an
      independent research scientist. Finally, because it is essential that a junior
      faculty member secure independent research funding, receiving this award from the
      NBF also represented a critical step in my career. The work that was funded by
      the NBF has led my laboratory down many new avenues of research, all of which
      have been exciting and rewarding.

PMID- 16086792
TI  - Assessment of the correlation of platelet morphology with in vivo recovery and
      survival.
AB  - BACKGROUND: There is continuing interest in the development of in vitro tests
      evaluating the in vivo function, recovery, and survival of platelets stored for
      transfusion. A recent forum concluded that no completely reliable test exists,
      although discoid morphology indicates a platelet's good health. We evaluated a
      novel device, the NAPSAC (Noninvasive Assessment of Platelet Shape and
      Concentration), designed to determine noninvasively the proportion of discoid
      platelets in a stored concentrate, as well as platelet concentration. STUDY
      DESIGN AND METHODS: Twenty-eight plateletapheresis concentrates stored 24 hours
      in PL-146 were evaluated. Percent discoid platelet results were correlated with
      radiolabeled autologous recovery and survival performed using 111Indium
      oxyquinoline and calculated using linear (L) and multiple-hit (M) models. pH of 8
      concentrates was raised at the end of storage with 6N NaOH. Platelet
      concentration measured by NAPSAC and Coulter Thrombocounter C was compared in 256
      plateletapheresis products. RESULTS: Percent discoid platelets at 24 hours did
      not correlate significantly with platelet recovery or survival (recovery L =
      0.29, M = 0.28; survival L = 0.16, M = 0.03). Raising the pH (mean 6.38 to 6.94)
      resulted in a significant increase in percent discoid platelets (21% to 41%).
      Platelet concentration values for both methods studied were linearly correlated
      with a slope of 1.01 +/- 0.03, r = 0.81. CONCLUSION: Percent discoid platelets
      was not predictive of posttransfusion platelet recovery or survival. The results
      suggest that non-discoid platelets may survive posttransfusion and even revert to
      discoid shape, since raising the pH approximately doubled the percent of discoid
      platelets. The NAPSAC was shown to be a reliable instrument for noninvasively
      determining platelet concentration in PL-146 concentrates.

PMID- 16086793
TI  - Protective human immunity as a vaccine discovery tool for falciparum malaria.
AB  - BACKGROUND: Plasmodium falciparum malaria remains a leading cause of morbidity
      and mortality in developing countries, and malaria-associated severe anemia is
      the major factor driving the high transfusion requirements in pediatric
      populations living in endemic areas. STUDY DESIGN AND METHODS: In this report, we
      identify and evaluate the targets of naturally acquired protective antibody
      responses in a cohort of n = 143 male volunteers residing in a P. falciparum
      holoendemic area of western Kenya. Volunteers were drug-cured of current malaria
      infection, blood was collected 2 weeks after treatment, and blood smears were
      collected weekly for 18 weeks. We identified and pooled plasma from the 10 most
      resistant (RP) and the 7 most susceptible individuals (SP) and utilized these
      pools in a differential screen of a P. falciparum cDNA expression library. We
      screened 550,000 clones and identified 7 clones that were uniquely recognized by
      RP but not by SP. Two clones encoded a C-terminal region polypeptide from rhoptry
      associated membrane antigen (RAMA-pr), a recently described rhoptry-associated
      membrane antigen. RESULTS: We measured RAMA-pr antibody levels in plasma obtained
      2 weeks after treatment. Individuals with detectable immunoglobulin G(1) anti
      RAMA-pr (n = 24) had fewer positive blood films (p < 0.003) and 43 percent lower
      density of parasitemia (p < 0.02) than individuals with undetectable (n = 115)
      antibody levels. CONCLUSION: RAMA-pr is a rationally identified vaccine candidate
      preferentially recognized by antibodies produced by humans with a high level of
      naturally acquired resistance to P. falciparum infection. Our results demonstrate
      that naturally acquired protective antibody responses are useful tools to
      identify vaccine candidates for falciparum malaria.

PMID- 16086794
TI  - Mechanisms of human immunodeficiency virus-1 latency.

PMID- 16086795
TI  - Complexities of the Dombrock blood group system revealed.
AB  - The Do(a) antigen was discovered after I began my career in immunohematology and
      I have been fortunate to be involved in several fascinating discoveries in the
      Dombrock blood group system. The Do(a) antigen and its antithetical antigen,
      Do(b), have a prevalence that makes them useful as genetic markers. The paucity
      of reliable anti-Do(a) and anti-Do(b) has prevented this potential from being
      realized; however, our ability to type for DO alleles at the DNA level has made
      it possible to test cohorts from different populations. In 1992, the Dombrock
      blood group system was expanded to include three phenotypically related antigens,
      Gy(a), Hy, and Jo(a), when it was discovered that the Gy(a-) phenotype was the
      null of the Dombrock system. Based on the knowledge that the Dombrock
      glycoprotein is attached to the RBC membrane via a glycosylphosphatidylinositol
      linkage and subsequent to the assignment of the corresponding gene to the short
      arm of chromosome 12, expressed sequence tags from terminally differentiating
      human erythroid cells were analyzed in silico to identify the DO gene. This
      allowed determination of the molecular basis of the various Do phenotypes and the
      realization that DO is identical to the gene encoding a mono-ADP
      ribosyltransferase, ART4. No enzymatic activity in RBCs has been demonstrated and
      the function of this glycoprotein, on the outside surface of RBCs, has yet to be
      determined. This review is a synthesis of our current knowledge of the Dombrock
      blood group system.

PMID- 16086796
TI  - Developing phage display tools for use in transfusion medicine.

PMID- 16086797
TI  - The role of endothelial activation in the pathogenesis of transfusion-related
      acute lung injury.

PMID- 16086798
TI  - Deciphering the function of the Rh family of proteins.

PMID- 16086800
TI  - International relevance.

PMID- 16086801
TI  - End of life care: a discursive analysis of specialist palliative care nursing.
AB  - AIM: The aim of this paper is to consider alternative approaches to service
      delivery for patients with chronic life-limiting illnesses other than cancer. It
      will also discuss the issues that arise when considering specialist palliative
      care services within a broader public health context in the United Kingdom.
      BACKGROUND: Contemporary specialist palliative care in the United Kingdom can be
      said to have two main client groups: the majority are people with a diagnosis of
      cancer, and a minority are those with a number of other chronic illnesses. From
      the evidence to date, patients dying from chronic, non-malignant disease
      experience a considerable number of unmet needs in terms of symptom control and
      psychosocial support. Although debates in the literature over the last decade
      have challenged the focus of specialist palliative care services on patients with
      a cancer diagnosis, only a minority of those with other chronic illnesses receive
      specialist palliative care services. DISCUSSION: Current models of specialist
      palliative care may not be the most appropriate for addressing the complex
      problems experienced by the many patients with a non-cancer diagnosis. We suggest
      that care should be structured around patient problems, viewing specialist
      palliative care as a service for those with complex end of life symptoms or
      problems. A role for innovative nurse-led care is proposed. CONCLUSION: Reframing
      the approach to specialist palliative care in the United Kingdom will require
      great effort on the part of all health and social care professionals, not least
      nurses. Critical and creative thinking are prerequisites to the development of
      new models of working. We suggest that a more coherent approach to research and
      education is required, in particular strategies that explore how patients and
      nurses can work together in exploring experiences of illness in order to develop
      more proactive approaches to care.

PMID- 16086799
TI  - Development of complement therapeutics for inhibition of immune-mediated red cell
      destruction.
AB  - A major objective of my National Blood Foundation (NBF)-funded proposal was to
      produce recombinant soluble forms of a complement regulatory protein called
      complement receptor 1 (CR1) that carries the Knops blood group system antigens to
      perform antibody neutralization studies. By generating these recombinant
      proteins, we were able to inhibit several Knops antibodies in patient serum
      samples, thereby demonstrating their usefulness for clinical use. Interestingly,
      the recombinant CR1 proteins generated through NBF funding were also found to
      strongly reduce complement-mediated red cell destruction in a mouse hemolytic
      transfusion model. In this review, I will outline our NBF-funded studies, give an
      overview of recent advances from our group and others in the development of
      complement therapeutics, and highlight their potential use in the transfusion
      medicine setting.

PMID- 16086802
TI  - Chinese nurses' use of non-pharmacological methods in children's postoperative
      pain relief.
AB  - AIM: This paper reports a study describing Chinese nurses' use of non
      pharmacological methods for relieving 6- to 12-year-old children's postoperative
      pain and factors related to this. BACKGROUND: Non-pharmacological methods are
      stated to be effective in relieving children's postoperative pain when used
      independently or in conjunction with medication. However, little is known about
      the use of these methods by Chinese nurses. METHODS: A questionnaire survey was
      carried out in 2002 with a convenience sample of 187 nurses working at 12
      surgical wards in five hospitals of Fujian Province, China. A Likert-type
      instrument was used, and the average response rate was 98%. Descriptive
      statistics and content analysis were used to analyse the data. RESULTS: The most
      commonly used non-pharmacological methods were giving preparatory information,
      comforting/reassurance, creating a comfortable environment, distraction, and
      positioning. Positive reinforcement and helping with daily activities were used
      less often, and transcutaneous electrical nerve stimulation was not used at all.
      Many nurse background factors were statistically significantly related to their
      use of pain alleviation methods. Furthermore, many factors limited their use of
      non-pharmacological methods, the most common being that there were too few nurses
      for the work that had to be done, followed by nurses' lack of knowledge about
      pain management. CONCLUSIONS: While Chinese nurses used versatile non
      pharmacological methods in school-aged children's postoperative pain relief,
      there remains a need for more education about pain management and for more
      frequent use of these methods in clinical care.

PMID- 16086803
TI  - Practice nurses and older people: a case management approach to care.
AB  - AIM: This paper reports on aspects of a study designed to answer the research
      questions: (i) To what extent do practice nurses use the five cyclical elements
      of a case management approach when caring for people aged over 75 years? (ii)
      What determines or deters practice nurses' use of the cyclical elements of a case
      management approach in caring for older people? BACKGROUND: Case management is an
      approach that uses a cyclical process of assessment, planning, implementation,
      monitoring and evaluation to provide systematic proactive care to people with
      complex health and social care needs. In England, specialist practice nurse case
      managers for older people have been piloted in ten primary care trusts and the
      posts are to be implemented nationally by 2008. No baseline work has, however,
      considered the applicability of developing the existing generalist practice nurse
      workforce. METHOD: A 26-item structured postal questionnaire was used to explore
      both practice nurses' use of a case management approach when working with older
      people, and what factors influenced the care provided. A random sample of 500
      practice nurses was selected from the Royal College of Nursing Practice Nurse
      Association member database. RESULTS: A 45% response rate was achieved. Practice
      nurses assessed, planned and implemented care, but reviewing medication
      opportunistically and evaluating the care were uncommon. A case management
      approach was significantly (P = 0.005) more likely to be used in on-going
      management activities than in one-off treatment room care. Practice nurses with
      postregistration education in district nursing were significantly (P = 0.016)
      more likely to refer patients to social care services. Lack of time and the
      central role of the general practitioner were the main reasons for not
      incorporating case management into practice. CONCLUSIONS. The extent to which
      practice nurses used elements of a case management approach was highly variable
      and influenced by individual professional expertise, the nature of the
      consultation and the practice nurse's position in the general practice.

PMID- 16086804
TI  - Stress in women with postpartum depression: a phenomenological study.
AB  - AIM: The aim of this paper is to report a study of the lived experience of
      postpartum stress among depressed Hong Kong Chinese mothers. BACKGROUND: Research
      consistently relates postpartum stress to the mood and well-being of mothers
      during the postpartum period. While several studies have used questionnaires to
      assess the stress levels of mothers or have identified stressors by asking them
      to list stressful events, the existing literature lacks in-depth information on
      the lived experience of postpartum stress from the perspective of the depressed
      mother. METHODS: The study adopted a phenomenological approach with a purposive
      sample of 11 depressed Hong Kong Chinese mothers at around the sixth postpartum
      month. In-depth interviews were conducted in Cantonese and focused on the stress
      the mothers experienced during the postpartum period up to the time of the
      interview. The data were collected in 2000. RESULTS: Living in a metropolitan
      city under the mixed and sometimes conflicting influences of cultures from the
      East and the West, Hong Kong Chinese mothers face a unique set of challenges
      which, if not properly managed, may cause stress and/or depression in the
      postpartum period. We identified five major postpartum stress themes amongst this
      group of women: parenting competence, the expectation-experience gap, baby-minder
      arrangements, childcare demands, and conflict with culture and tradition.
      CONCLUSIONS: Health care staff should give anticipatory guidance to mothers and
      their spouses about the culturally prescribed set of rules that proved stressful.
      Antenatal education classes need to enhanced, and support is needed to help this
      population of women manage and overcome the challenges in the postpartum period.

PMID- 16086805
TI  - Decision-making tree for women considering hysterectomy.
AB  - AIMS: This paper reports on a study carried out to establish a decision tree
      model to describe how women in Taiwan make the decision whether or not to have a
      hysterectomy. In addition, we examined the predictability of the decision-tree
      model. BACKGROUND: Hysterectomy is the second most common surgical procedure
      performed worldwide. Medical professionals believe that the operation can relieve
      pain and prevent cervical cancer, thus improving a woman's quality of life. While
      most physicians advise hysterectomy even for benign uterine conditions, feminists
      decry the belief that the uterus has no purpose, believing that it is an
      important symbol of womanhood. METHODS: The study was conducted in two phases.
      Phase I, the model development phase, was carried out to generalize data from a
      qualitative study of 14 women and to establish a tree model outlining their
      decision to proceed with hysterectomy. The second phase was the model prediction
      phase that applied inductive and deductive methods to data analysis and
      development of the decision-tree model. The model tree was then tested with 18
      women who were deciding whether or not to undergo hysterectomy. Using the
      decision-making tree, we studied the women's thought processes and analysed their
      primary concerns. The study was carried out in 1999-2001. RESULTS: The study
      determined 13 criteria that Taiwanese women use when deciding about having a
      hysterectomy. Developed in accordance with Gladwin's methodology, the model tree
      successfully predicted 90% of decisions whether or not to have a hysterectomy.
      CONCLUSIONS: Nurses working in gynaecological services should understand how
      women decide to undergo hysterectomy so that the proper counselling and follow-up
      can be provided. With further testing, our decision tree may help in this
      process.

PMID- 16086806
TI  - Nursing and cancer support groups.
AB  - AIM: The aim of this paper is to review the evidence on the effectiveness of
      support groups by reporting a meta-analysis of randomized controlled trials
      evaluating support groups for patients with cancer. BACKGROUND: One of the most
      important nursing aims is to give patients with cancer emotional support and
      strengthen their adaptation to the disease. According to the literature, support
      groups for these patients are beneficial. METHODS: Original studies from 14
      databases published during the past 20 years in peer review journals were
      selected. Twenty studies with a randomized clinical trial design constituted the
      final meta-analysis sample. Methodological quality of the selected articles was
      checked using the Jadad Scale and the Checklist of Consort Statement. Demographic
      data were analysed using the SPSS program, and the heterogeneity calculation and
      effect size were analysed using the Rev-Man 4-.1-Metaview program. FINDINGS: The
      results indicate that participation in a support group is associated with
      significant improvements in a patient's emotional state (depression and anxiety),
      illness adaptation, quality of life, and marital relationships. CONCLUSION:
      Support group participation for patients with cancer has a positive impact in
      various areas. Nurses should promote participation as a crucial part of their
      care.

PMID- 16086807
TI  - Women, men and coronary heart disease: a review of the qualitative literature.
AB  - AIM: This paper presents a review of the qualitative literature which examines
      the experiences of patients with coronary heart disease. The paper also assesses
      whether the experiences of both female and male patients are reflected in the
      literature and summarizes key themes. BACKGROUND: Understanding patients'
      experiences of their illness is important for coronary heart disease prevention
      and education. Qualitative methods are particularly suited to eliciting patients'
      detailed understandings and perceptions of illness. As much previous research has
      been 'gender neutral', this review pays particular attention to gender. METHODS:
      Published papers from 60 qualitative studies were identified for the review
      through searches in MEDLINE, EMBASE, CINAHL, PREMEDLINE, PsychINFO, Social
      Sciences Citation Index and Web of Science using keywords related to coronary
      heart disease. FINDINGS: Early qualitative studies of patients with coronary
      heart disease were conducted almost exclusively with men, and tended to
      generalize from 'male' experience to 'human' experience. By the late 1990s this
      pattern had changed, with the majority of studies including women and many being
      conducted with solely female samples. However, many studies that include both
      male and female coronary heart disease patients still do not have a specific
      gender focus. Key themes in the literature include interpreting symptoms and
      seeking help, belief about coronary 'candidates' and relationships with health
      professionals. The influence of social roles is important: many female patients
      have difficulties reconciling family responsibilities and medical advice, while
      male patients worry about being absent from work. CONCLUSIONS: There is a need
      for studies that compare the experiences of men and women. There is also an
      urgent need for work that takes masculinity and gender roles into account when
      exploring the experiences of men with coronary heart disease.

PMID- 16086808
TI  - Use of complex adaptive systems metaphor to achieve professional and
      organizational change.
AB  - AIM: This paper uses the experiences of a programme designed to bring about
      change in performance of public health nurses (health visitors and school nurses)
      in an inner city primary care trust, to explore the issues of professional and
      organizational change in health care organizations. BACKGROUND: The United
      Kingdom government has given increasing emphasis to programmes of modernization
      within the National Health Service. A central facet of this policy shift has been
      an expectation of behaviour and practice change by health care professionals.
      METHODS: Change was brought about through use of a Complex Adaptive Systems
      approach. This enabled change to be seen as an inclusive, evolving and
      unpredictable process rather one which is linear and mechanistic. The paper
      examines in detail how the use of concepts and metaphors associated with Complex
      Adaptive Systems influenced the development of the programme, its implementation
      and outcomes. FINDINGS: The programme resulted in extensive change in
      professional behaviour, service delivery and transformational change in the
      organizational structures and processes of the employing organization. This gave
      greater opportunities for experimentation and innovation, leading to new
      developments in service delivery, but also meant higher levels of uncertainty,
      responsibility, decision-making and risk management for practitioners.
      CONCLUSION: Using a Complex Adaptive Systems approach was helpful for developing
      alternative views of change and for understanding why and how some aspects of
      change were more successful than others. Its use encouraged the confrontation of
      some long-standing assumptions about change and service delivery patterns in the
      National Health Service, and the process exposed challenging tensions within the
      Service. The consequent destabilising of organizational and professional norms
      resulted in considerable emotional impacts for practitioners, an area which was
      found to be underplayed within the Complex Adaptive Systems literature. A Complex
      Adaptive Systems approach can support change, in particular a recognition and
      understanding of the emergence of unexpected structures, patterns and processes.
      The approach can support nurses to change their behaviour and innovate, but
      requires high levels of accountability, individual and professional creativity.

PMID- 16086809
TI  - The skill mix practice model for nursing: measuring outcome.
AB  - AIM: This paper reports a study examining the outcome of personnel costs and
      quality of care after implementing the skill mix practice model for nursing.
      BACKGROUND: In response to ever-tightening government budgets and changes in
      health insurance reimbursement, it may be necessary for hospitals to reassess
      their practice models to remain competitive and maintain quality of care. METHOD:
      Using a pre- and post-test quasi-experimental design with questionnaires,
      participants were recruited at a teaching hospital in Taiwan. Questions were
      included on both patient satisfaction with nursing care and nurse satisfaction
      with nursing aides. The data were collected in 2003. RESULTS: The cost of
      implementing the skill mix practice model with 22 nurses and seven nursing aides
      was 2.7% lower than when only using 25 nurses. In addition, there was a
      statistically significant difference in patient satisfaction and in nurse
      satisfaction with the performance of the aides. There was no statistically
      significant difference in the pre- and post-test outcome measures of both the
      incidence of falls and the medication error rate. CONCLUSION: To decrease costs
      and increase quality of care, the skill mix practice model is worthy of
      consideration for clinical nursing care. This study presents an investigation of
      the first hospital implementation of the skill mix practice model for nursing in
      Taiwan, and the results of which can serve as a reference model for hospital
      nursing practice reform.

PMID- 16086810
TI  - The ethics of relation: public health nurses and child protection clients.
AB  - AIM: The aim of this paper is to show how a framework of relational ethics may be
      used in establishing trusting relationships with at-risk families. BACKGROUND:
      Public health nurses have historically carried out assessment and monitoring of
      parenting within the family home, particularly with at-risk families. In this
      role, they are placed in the position of simultaneously supporting and policing
      the family. A trusting relationship may be difficult to develop if parents feel
      threatened by the surveillance aspect of home visiting and the threat of action
      (such as removal of children) being taken against the family. DISCUSSION:
      Development of optimal trust relationships may be a challenge when families are
      experiencing powerlessness and oppression. The four themes of relational ethics-
      mutual respect, engaged interaction, embodiment and creating environment--provide
      a framework for developing trusting relationships with families. CONCLUSION: It
      is possible to have a moral and trusting relationship with at-risk families, but
      this needs to based on critical self-reflection by nurses and mutually respectful
      nurse-family relations.

PMID- 16086811
TI  - Adapt or adopt: developing and transgressing the methodological boundaries of
      grounded theory.
AB  - AIMS: While acknowledging that there is an existing debate regarding the nature
      of grounded theory, the aim of this paper is to highlight a number of common and
      key areas/issues where adaptation/adoption of Glaserian grounded theory in
      nursing-related studies often occurs. These issues are: the differences between
      conceptual description and conceptual theory; beginning the study with a 'general
      wonderment' or a more defined research question; establishing the credibility of
      the theory; identifying a basic psycho-social process and emerging vs. forcing.
      BACKGROUND: Since the development and introduction of grounded theory in 1967,
      the number of studies, in a wide range of disciplines including nursing, that
      purport to be using a grounded theory method has grown enormously. While Glaser
      and Strauss acknowledged then that it was entirely appropriate for the
      methodology to evolve and develop, some of the studies that claim to be based on
      grounded theory methodology share little methodological similarity, and at times,
      bear only a passing resemblance to Glaserian grounded theory. DISCUSSION: Some
      methodological transgressions in papers that purport to be grounded theory
      studies are such that it would be inaccurate to term the resulting method
      grounded theory at all. Instead such studies are more accurately thought of as a
      form of qualitative data analysis. Such transgressions include a study that has
      no evidence of conceptualization; one that does not identify a basic psycho
      social process; and one that moves from 'emerging' to 'forcing'. Other
      methodological adaptations of grounded theory, such as beginning the study with
      more than a general wonderment and broadening the approach to establishing the
      credibility of the theory, are more in keeping with Glaser and Strauss' position
      on the evolution of the method. In such cases, it is necessary to distinguish
      such methods from 'pure' Glaserian grounded theory, and it would be prudent and
      methodologically accurate to describe the resulting method as 'modified' grounded
      theory.

PMID- 16086816
TI  - Glomerular structural changes in pregnant, diabetic, and pregnant-diabetic rats.
AB  - Kidneys enlarge both during pregnancy and in diabetes. The enlargement and
      morphology of glomeruli was studied during pregnancy and in diabetes in order to
      examine possible similarities, differences, and interactions in the growth in
      these conditions. Morphometric investigations were performed on glomeruli in
      pregnant rats, in rats with 2 weeks' diabetes, and in pregnant-diabetic rats.
      Kidneys were enlarged 22% in the midterm pregnant rats compared with controls,
      74% in diabetic rats, and a further 21% in pregnant-diabetic rats. Glomerular
      volume was enlarged by 26% during midterm pregnancy in normal animals. Diabetes
      induced an enlargement in glomerular volume of 58% and a further 18% in midterm
      diabetic animals due to pregnancy. Within the glomerulus, pregnancy in normal
      animals induced minor non-significant changes. Diabetes induced significant
      increase in several parameters: mesangial volume and cell volume, capillary and
      glomerular basement membrane volume, capillary wall surface area, foot process
      width, filtration slit length, and nuclear number. Pregnancy in diabetic animals
      induced no significant additional changes. In conclusion, kidney enlargement in
      pregnancy shows very few glomerular changes in either normal or diabetic animals.
      Enlargement of glomeruli in diabetes involves hypertrophy and hyperplasia
      concurrent with several morphological changes within the glomerulus.

PMID- 16086817
TI  - Histopathological grading of laryngectomy specimens.
AB  - A material comprising 118 laryngectomy specimens, prepared by whole organ serial
      sectioning, was analyzed to determine the prognostic significance of
      histopathological tumor grading. No statistically significant association could
      be demonstrated between grading and a number of clinical and histopathological
      variables, including pathological staging, lymph node metastases or recurrence
      rate. The study supports the contention that the prognostic value of
      histopathological grading of laryngeal squamous cell carcinoma remains uncertain
      and unproven. Serial sections of the whole organ, processed by routine laboratory
      techniques, remain important for studying tumor extension but do not contribute
      to establishing histopathological grading as a significant prognostic parameter.

PMID- 16086818
TI  - Porcine humoral immune responses to multiple injections of murine monoclonal
      antibodies.
AB  - In humans and cattle, multiple injections of murine monoclonal antibodies (m
      mAbs) induce anti-mouse antibody responses. The objectives of the present study
      were to investigate whether a similar response could be seen when pigs were
      subjected to m-mAb therapy, and to study the kinetics of such a response. In two
      separate animal experiments, long-term treatment was performed with m-mAbs at low
      dose levels and therapeutic levels, respectively. Two specific m-mAbs that
      recognized cognate antigen in the pigs (CD4 and CD8 surface antigens on T
      lymphocytes) and two irrelevant control m-mAbs having no cognate antigen in the
      pigs were used. Enzyme-linked immunosorbent assays (ELISA) were used to
      quantitate the circulating m-mAbs, as well as the induced pig anti-mouse
      antibodies (PAMA), in serum samples from m-mAb-treated pigs. As expected, we
      generally saw vigorous PAMA responses within 10 days after the start of m-mAb
      treatment with the specific m-mAbs. However, the different mAbs showed striking
      differences in the kinetics and levels of PAMA responses, differences that might
      be ascribed to the m-mAb formulation and epitope specificity. In conclusion,
      treatment of pigs with m-mAbs against T-cell surface antigens induced rapid PAMA
      responses. This may influence and possibly decrease the effect of the m-mAb
      treatment by narrowing the time period where m-mAbs can efficiently be used for
      cell depletion.

PMID- 16086819
TI  - Effect of temporin A modifications on its cytotoxicity and antimicrobial
      activity.
AB  - Temporin A (TA), a short alpha-helical antimicrobial peptide isolated from the
      skin of the frog Rana temporaria, is effective against a broad spectrum of Gram
      positive bacteria, including methicillin-resistant Staphylococcus aureus and
      vancomycin-resistant Enterococcus faecium strains. TA interacts directly with the
      cell membrane of the microorganism and it has been reported to be non-toxic to
      erythrocytes at concentrations that are antimicrobial. Less is known about the
      effects on the viability and growth of nucleated eukaryotic cells. In this study
      we have tested antibacterial and growth-inhibitory properties of TA, its dimeric
      analogue (TAd), and all-L (TAL L512) and all-D (TAD L512) enantiomeric
      derivatives of modified TA towards S. aureus and cultured human keratinocytes,
      respectively. All molecules were antibacterial at concentrations from 1.5 microM
      to 10 microM. In keratinocyte cultures, TAD L512, as well as TAd, showed
      cytotoxicity. The original TA and TAL L512 did not affect the viability of the
      cells at their bacteriolytic concentrations. The growth of keratinocytes in low-
      and high-calcium media was only slightly inhibited by temporins at concentrations
      which were antibacterial to S. aureus. This suggests that original TA and its
      modification, TAL L512, are promising molecules against multiresistant bacterial
      infections.

PMID- 16086820
TI  - Ultrastructure and chromogranin A immunogold labelling of ECL cell carcinoids.
AB  - Poorly differentiated neuroendocrine cells can be difficult to recognise.
      Sensitive methods are needed to label cells that have lost their ultrastructural
      features and have reduced concentrations of neuroendocrine markers. In gastric
      neoplasms, enterochromaffin-like cells might dedifferentiate and lose their
      characteristic granules and secretory vesicles, making detection of such cells
      increasingly difficult. However, chromogranin A (CgA) immunogold labelling could
      provide sensitive and specific detection of gastric neuroendocrine cells. We
      present ultrastructural findings, CgA immunogold labelling as well as
      conventional immunohistochemical findings of two human enterochromaffin-like cell
      carcinoids. Electron-dense granules of poorly differentiated cells were less
      intensely labelled than granules in well-differentiated cells. Granules with
      atypical shape as well as punctuate granules previously found in neuroendocrine
      neoplasms were also CgA labelled. The CgA labelling efficacy after antigen
      retrieval in an alkaline solution was higher after heating in an autoclave at 135
      degrees C compared to a microwave at 100 degrees C for both granules and
      secretory vesicles without significant deterioration of the ultrastructure. In
      conclusion, the use of CgA immunogold labelling could ensure a specific
      classification of cells with neuroendocrine granules and be a supplement to
      immunohistochemical examination of poorly differentiated tumours.

PMID- 16086821
TI  - Trimethylamine and trimethylamine oxide levels in normal women and women with
      bacterial vaginosis reflect a local metabolism in vaginal secretion as compared
      to urine.
AB  - The smell of rotten fish is one of the characteristics of bacterial vaginosis
      (BV), and is due to trimethylamine (TMA). Trimethylamine can be found in human
      urine, although most of it occurs as the nonvolatile oxide (TMAO) form. The
      fraction TMA/TMAO can be expected to be the same in different body fluids if no
      local production of TMA occurs. In women with BV, TMAO in the vaginal fluid is
      expected to be chemically reduced by the local bacterial flora to the much more
      odorous TMA. We have therefore studied the local vaginal production of TMA in
      vaginal secretion compared to the general TMA-TMAO metabolism that was measured
      in urine using gas chromatography. Both vaginal fluid and random urine samples
      were collected from women, with and without BV, attending a Swedish clinic for
      sexually transmitted diseases, and these samples were analyzed for TMA and TMAO.
      The results show that a local production of TMA occurs in the vagina that is not
      part of the general metabolism of TMA-TMAO.

PMID- 16086822
TI  - Aerococcus urinae: polyphasic characterization of the species.
AB  - A polyphasic characterization of Aerococcus urinae is presented. In this study
      the intraspecies relationships between 26 strains of varying geographical origin
      were examined by phenotypic tests, ribotyping and multilocus enzyme
      electrophoresis. The results demonstrated two main phenotypic patterns that could
      be distinguished in tests for hydrolysis of aesculin, and acid production from
      amygdalin and salicin. Strains were either negative (n=19) or positive (n=6) in
      these tests. One strain had a deviating pattern. Heterogeneity within the 19
      pattern I strains was demonstrated especially by phenotypic tests (acid
      production from ribose, mannitol, sorbitol, sucrose and D-arabitol) and by
      multilocus enzyme electrophoresis. However, DNA sequence analysis of the 16S rRNA
      (n=7) and gyrB genes (n=3) from strains representing the two main patterns showed
      no variation in sequences among strains. Comparison of A. urinae and
      representatives of related taxa by 16S rDNA sequence analysis showed that the
      taxon is related to, but distinct from, other Aerococcus spp.

PMID- 16086823
TI  - Profiles of NK, NKT cell activation and cytokine production following vaccination
      against hepatitis B.
AB  - Human natural killer (NK) cells (CD56+ CD3-) represent crucial components of the
      innate immune system especially against viral infections and because their
      activation can modulate the outcome of the adaptive immune response. NKT cells
      (CD56+CD3+), a lymphocyte T population characterized by expression of surface
      markers of NK cells, are known to be abundant in the liver and their activation
      could be associated with hepatic injury. Using three-color flow cytometry to
      measure surface receptors and intracellular cytokines, we have explored early
      activation signals and cytokine production in NK and NKT cells within a group of
      hepatitis B vaccinated and non-vaccinated individuals. A specific increase of the
      CD56bright cell population, the activation receptor CD69 and IFN-gamma, was
      observed in NK cells following incubation with recombinant HBsAg in responders to
      vaccination. Comparable results were observed in NKT cells showing an increment
      of CD69, CD25, IL-2 and IFN-gamma expression in responder subjects. These
      parameters were statistically diminished in non-responder individuals (p<0.05) in
      both groups of cells. These results demonstrate a diminished activation of these
      cells in non-responders to the vaccine, suggesting that NK and NKT cells play an
      important role in the immune response following hepatitis B vaccination.

PMID- 16086824
TI  - Genetic diversity of bovine viral diarrhoea viruses (BVDV) in Denmark during a 10
      year eradication period.
AB  - A 243 base-pair fragment of the 5'- untranslated region (5'-UTR) of bovine viral
      diarrhoea virus (BVDV) was RT-PCR amplified from tissue samples (after one
      passage) or from plasma collected from Danish cattle in 1962 (1), 1993 (7), or in
      2002-03 (28) when BVD was almost extinct as a result of a 6-year eradication
      programme. The PCR products were sequenced and phylogenetically analysed. All 36
      samples were BVDV species 1 (BVDV-1), 29 sequences belonged to the BVDV 1d
      subtype, 6 to the BVDV 1b subtype, and one sequence to the BVDV 1e subtype. While
      all samples from 1993 and 1962 were of 1d subtype, the samples collected in 2002
      2003 belonged to 1d (22 samples), 1b (5 samples) and 1e (1 sample) subtypes. In
      five herds, materials from two animals were obtained for PCR analysis. In four of
      five herds the sequences of the two viruses were identical, but in one herd the
      obtained sequences belonged to two different subtypes. Routine analysis detected
      11 PI calves older than 2 months of age. For early detection of infected calves
      it is recommended that antigen ELISA be replaced by PCR detection. Here we
      present the first sequence analysis of Danish BVDV strains.

PMID- 16086825
TI  - High prostate cancer mortality in Norway: influence of Cancer Registry
      information?
AB  - Norway has among the highest prostate cancer mortality rates in the world. The
      aim of the present project was to assess whether this can be explained by the
      unique routine procedure of information transfer from the Cancer Registry of
      Norway (CR) to the Norwegian Cause of Death Registry (COD Registry). Norwegian
      prostate cancer patients deceased during 1996 were identified (n=2012). The
      information basis of the official mortality statistics was reviewed by two
      physicians, who independently identified the underlying cause of death, primarily
      prostate cancer or not, supplemented by consensus of two other physicians. The
      coding was done in two steps; first without, then with CR information. Project
      physicians identified 1063 deaths from prostate cancer as compared to the
      official number of 1161, with discrepancy as to prostate cancer death in 126
      deceased. Information from the CR increased the project's age-adjusted (world
      standard population) prostate cancer mortality rate by less than 1% (from 22.7 to
      22.9 per 100,000). In conclusion, the high rates of prostate cancer mortality in
      Norway could not be explained by information transfer from the CR to the COD
      Registry.

PMID- 16086826
TI  - Pulmonary adenocarcinoma with micropapillary component: an immunohistochemical
      study. Case report.
AB  - Micropapillary carcinoma has been described in various organs, including the
      breast, urinary bladder, ovary and lung. We here present a case of pulmonary
      micropapillary carcinoma in a 72-year-old Japanese man who died of respiratory
      failure and septic shock, following which autopsy was performed. A mass measuring
      2.5 x 2.5 x 2.5 cm was observed in the left lower lobe of the lung. The tumor
      showed moderately differentiated papillary adenocarcinoma with a focal
      micropapillary component. Carcinomatous lymphangiosis was also observed in the
      left lung and metastatic lesions were observed in the bilateral lung, liver,
      vertebra, muscle layer of the urinary bladder, right adrenal gland, spleen and
      lymph nodes. The micropapillary component was predominant at some metastatic
      sites. Immunohistochemically, both the adenocarcinoma and micropapillary
      components were positive for cytokeratin (CK) 7, CK19, TTF (thyroid transcription
      factor)-1, carcinoembryonic antigen (CEA) and surfactant apoprotein A (SP-A), and
      negative for CK20, estrogen receptor, progesterone receptor, uroplakin III, and
      CA125. The invasive area of the conventional adenocarcinoma component contained a
      large number of myofibroblasts, whereas the stroma of the micropapillary
      component contained a small number of myofibroblasts. However, no myofibroblasts
      were observed in the stroma of the central core of the non-invasive
      micropapillary carcinoma. Several lymphatic invasions by neoplastic cells were
      identified in the peripheral area of the micropapillary component using D2-40
      antibody. The immunohistochemical profile may be helpful in determining the
      primary location of the neoplasm containing micropapillary features.
      Myofibroblasts are present in the stroma of the invasive neoplastic nests in the
      micropapillary component as well as the conventional adenocarcinoma component,
      and D2-40 monoclonal antibody may be useful for evaluating the lymphatic invasion
      of pulmonary micropapillary carcinoma.

PMID- 16086827
TI  - Atraumatic rupture of the spleen associated with hemophagocytic syndrome and
      isolated splenic peliosis. Case report.
AB  - Atraumatic rupture of the spleen is an uncommon condition that may be associated
      with various etiologies. The hemophagocytic syndrome (HS) and isolated splenic
      peliosis are two rare conditions, each of which has previously been described in
      association with splenic rupture. We describe a unique case of atraumatic splenic
      rupture in which concurrent HS and splenic peliosis were diagnosed following
      splenectomy. Given that both these rare conditions have probably caused the
      splenic rupture, a possible association between these entities is discussed.

PMID- 16086828
TI  - Reactive hyperplasia with giant follicles in lymph node lesions from systemic
      lupus erythematosus patients. Report of three cases.
AB  - Lymph node enlargement is common in active systemic lupus erythematosus (SLE), a
      disease that is characterized by well-defined clinical criteria. Histologically,
      although lymphadenopathy associated with SLE exhibits marked histological
      diversity and occasionally shows atypical lymphoproliferative disorders, there
      has not been any description of the histopathological features of reactive lymph
      node hyperplasia with giant follicles (RHGF). We here report three such cases.
      The subjects were a 23-year-old Japanese female, a 44-year-old Japanese female
      and a 49-year-old Japanese male. All three patients initially presented with
      systemic lymphadenopathy. They also had systemic symptoms and abnormal laboratory
      findings indicating active disease, although two patients did not fulfill the
      diagnostic criteria for SLE at lymph node biopsy. Histologically, three lesions
      were characterized by numerous enlarged, coalescing lymphoid follicles with
      distortion rather than effacement of the lymph node architecture. By in situ
      hybridization, Epstein-Barr virus (EBV) genomes were demonstrated in two cases.
      The present three cases indicate that lymphadenopathy associated with SLE
      representing RFGH should be differentiated from the early stage of HIV-related
      lymphadenopathy as well as follicular lymphoma, particularly the floral variant.
      The authors would like to stress that the RHGF which is described in the present
      study should be listed in the pathohistology of SLE lymphadenopathy.

PMID- 16086829
TI  - Nonspecific granulomatous prostatitis with calculous ductal ectasia and extensive
      Paneth cell-like epithelial metaplasia. Case report.
AB  - We present a case of nonspecific granulomatous prostatitis in combination with
      calculous ductal ectasia and extensive epithelial Paneth cell-like metaplasia in
      a TURP-specimen. Our report highlights the importance of calculous ductal
      obstruction and stasis of secretions in the etiopathogenesis of this type of
      prostatitis. The observed extensive Paneth cell-like metaplastic change in
      adjacent epithelial cells most likely represents a phenotypic adaptive mechanism
      directed against foreign antigens and nondegradable lipids in the stagnant
      intraluminal debris.

PMID- 16086831
TI  - A comparative review of estimates of the proportion unchanged genes and the false
      discovery rate.
AB  - BACKGROUND: In the analysis of microarray data one generally produces a vector of
      p-values that for each gene give the likelihood of obtaining equally strong
      evidence of change by pure chance. The distribution of these p-values is a
      mixture of two components corresponding to the changed genes and the unchanged
      ones. The focus of this article is how to estimate the proportion unchanged and
      the false discovery rate (FDR) and how to make inferences based on these
      concepts. Six published methods for estimating the proportion unchanged genes are
      reviewed, two alternatives are presented, and all are tested on both simulated
      and real data. All estimates but one make do without any parametric assumptions
      concerning the distributions of the p-values. Furthermore, the estimation and use
      of the FDR and the closely related q-value is illustrated with examples. Five
      published estimates of the FDR and one new are presented and tested.
      Implementations in R code are available. RESULTS: A simulation model based on the
      distribution of real microarray data plus two real data sets were used to assess
      the methods. The proposed alternative methods for estimating the proportion
      unchanged fared very well, and gave evidence of low bias and very low variance.
      Different methods perform well depending upon whether there are few or many
      regulated genes. Furthermore, the methods for estimating FDR showed a varying
      performance, and were sometimes misleading. The new method had a very low error.
      CONCLUSION: The concept of the q-value or false discovery rate is useful in
      practical research, despite some theoretical and practical shortcomings. However,
      it seems possible to challenge the performance of the published methods, and
      there is likely scope for further developing the estimates of the FDR. The new
      methods provide the scientist with more options to choose a suitable method for
      any particular experiment. The article advocates the use of the conjoint
      information regarding false positive and negative rates as well as the proportion
      unchanged when identifying changed genes.

PMID- 16086832
TI  - Anti-Fas mAb-induced apoptosis and cytolysis of airway tissue eosinophils
      aggravates rather than resolves established inflammation.
AB  - BACKGROUND: Fas receptor-mediated eosinophil apoptosis is currently forwarded as
      a mechanism resolving asthma-like inflammation. This view is based on
      observations in vitro and in airway lumen with unknown translatability to airway
      tissues in vivo. In fact, apoptotic eosinophils have not been detected in human
      diseased airway tissues whereas cytolytic eosinophils abound and constitute a
      major mode of degranulation of these cells. Also, Fas receptor stimulation may
      bypass the apoptotic pathway and directly evoke cytolysis of non-apoptotic cells.
      We thus hypothesized that effects of anti-Fas mAb in vivo may include both
      apoptosis and cytolysis of eosinophils and, hence, that established eosinophilic
      inflammation may not resolve by this treatment. METHODS: Weeklong daily allergen
      challenges of sensitized mice were followed by airway administration of anti-Fas
      mAb. BAL was performed and airway-pulmonary tissues were examined using light and
      electron microscopy. Lung tissue analysis for CC-chemokines, apoptosis, mucus
      production and plasma exudation (fibrinogen) were performed. RESULTS: Anti-Fas
      mAb evoked apoptosis of 28% and cytolysis of 4% of eosinophils present in
      allergen-challenged airway tissues. Furthermore, a majority of the apoptotic
      eosinophils remained unengulfed and eventually exhibited secondary necrosis. A
      striking histopathology far beyond the allergic inflammation developed and
      included degranulated eosinophils, neutrophilia, epithelial derangement, plasma
      exudation, mucus-plasma plugs, and inducement of 6 CC-chemokines. In animals
      without eosinophilia anti-Fas evoked no inflammatory response. CONCLUSION: An
      efficient inducer of eosinophil apoptosis in airway tissues in vivo, anti-Fas mAb
      evoked unprecedented asthma-like inflammation in mouse allergic airways. This
      outcome may partly reflect the ability of anti-Fas to evoke direct cytolysis of
      non-apoptotic eosinophils in airway tissues. Additionally, since most apoptotic
      tissue eosinophils progressed into the pro-inflammatory cellular fate of
      secondary necrosis this may also explain the aggravated inflammation. Our data
      indicate that Fas receptor mediated eosinophil apoptosis in airway tissues in
      vivo may cause severe disease exacerbation due to direct cytolysis and secondary
      necrosis of eosinophils.

PMID- 16086833
TI  - Epidemiologic study of chronic hepatitis B virus infection in male volunteer
      blood donors in Karachi, Pakistan.
AB  - BACKGROUND: The magnitude of chronic infection with hepatitis B virus (HBV)
      varies substantially between the countries. A better understanding of incidence
      and/ or prevalence of HBV infection and associated risk factors provides insight
      into the transmission of this infection in the community. The purpose of this
      investigation was to estimate the prevalence of and to identify the risk factors
      associated with chronic infection with HBV, as assessed by HBV surface antigen
      (HBsAg) positivity, in asymptomatic volunteer male blood donors in Karachi,
      Pakistan. METHODS: Consecutive blood donations made at the two large blood banks
      between January 1, 1998 and December 31, 2002 were assessed to estimate the
      prevalence of HBsAg positivity. To evaluate the potential risk factors, a case
      control study design was implemented; cases (HBsAg positives) and controls (HBsAg
      negatives), were recruited between October 15, 2001 and March 15, 2002. A pre
      tested structured questionnaire was administered through trained interviewers to
      collect the data on hypothesized risk factors for HBV infection. Sera were tested
      for HBsAg using commercially available kits for enzyme linked Immunosorbant assay
      III. RESULTS: HBsAg prevalence in the male volunteer blood donors was 2.0 %
      (7048/351309). Multivariate logistic regression analysis showed that after
      adjusting for age and ethnicity, cases were significantly more likely than
      controls to have received dental treatment from un-qualified dental care provider
      (adjusted odds ratio (OR) = 9.8; 95% confidence interval (CI): 2.1, 46.1), have
      received 1-5 injections (adjusted OR = 3.3; 95% CI: 1.1, 9.6), more than 5
      injections (adjusted OR = 1.4; 95% CI: 1.4, 12.7) during the last five years or
      have received injection through a glass syringe (adjusted OR = 9.4; 95% CI: 2.6,
      34.3). Injury resulted in bleeding during shaving from barbers (adjusted OR =
      2.3; 95% CI: 1.1, 4.8) was also significant predictor of HBsAg positivity.
      CONCLUSION: Prevalence of HBsAg positivity in the male volunteer blood donors in
      Karachi was 2%. Infection control measures in health-care settings including safe
      injection practices and proper sterilization techniques of medical instruments
      and education of barbers about the significance of sterilization of their
      instruments may reduce the burden of HBV infection in this and similar settings.
      There is also an urgent need of developing locally relevant guidelines for
      counseling and management of HBsAg positive blood donors.

PMID- 16086834
TI  - Case-control study on analgesics and nephropathy (SAN): protocol.
AB  - BACKGROUND: The association between intake of non-phenacetin-containing
      analgesics and the occurrence of chronic renal failure is still controversially
      discussed. A new epidemiologic study was planned and conducted in Germany and
      Austria. METHODS/DESIGN: The objective of the international, multicenter case
      control study was to evaluate the association between end-stage renal disease
      (ESRD) and use of non-phenacetin-containing analgesics with particular emphasis
      on combined formulations. A targeted sample of 1000 new (incident) dialysis
      patients, aged less than 50 years, was planned to recruit between January 1, 2001
      and December 31, 2004. The age limit was chosen to avoid contamination of the
      study population with phenacetin-containing analgesics to the extent possible.
      Four control subjects per ESRD case, matched by age, sex, and region were
      selected from the population living in the region the case came from. Lifetime
      exposure to analgesics and potential renal risk factors were recorded in a single
      face-to-face interview. A set of aids was introduced to reinforce the memory of
      study participants. A standardized, pre-tested interview questionnaire
      (participants), a medical documentation sheet (physicians in dialysis centres), a
      logbook for all activities (dialysis centres) were used to collect the necessary
      data. Quality management consisted of the standardized procedures, (re-) training
      and supervision of interviewers, regular checks of all incoming data for
      completeness and plausibility. The study is scientifically independent and
      governed by a international Scientific Advisory Committee that bridged the gap
      between the sponsoring companies and the investigators. Also other advisory
      groups assisted the managing committee of the study. All relevant German and
      Austrian nephrological associations supported the study, and the study design was
      carefully reviewed and approved by the Kidney Foundation of Germany. DISCUSSION:
      The study is expected to answer the main research question by end 2005. There is
      however a high potential for various biases that we tried to address with
      adequate measure. One limitation however cannot be overcome: The methodologically
      needed age-limitation of the study will make it not easy to generalize the
      results to age groups over 50 years. It might be suggested to repeat the study
      for persons over 50 years in 10 years when contamination with phenacetin use
      early in life is likely to be outgrown.

PMID- 16086835
TI  - Screening and identification of differentially expressed transcripts in
      circulating cells of prostate cancer patients using suppression subtractive
      hybridization.
AB  - BACKGROUND: Tumor metastasis and changes in host immunosurveillance are important
      components in cancer development. Tumor cell invasion into the bloodstream is an
      essential step for systemic metastasis. Currently, the detection of tumor cells
      in the circulation is mainly dependent upon the utilization of known epithelial
      cell markers. However, expression of these molecules is not limited to cancer
      patients; healthy people also have a small number of epithelial cells in their
      circulation. Utilizing these markers to detect circulating tumor cells (CTCs)
      cannot adequately explain the mechanisms of tumor cell survival or their
      development of metastatic potential in peripheral blood. The immune system can
      also evolve along with the cancer, actually promoting or selecting the outgrowth
      of tumor variants. Unfortunately, both metastasis and immunosurveillance remain
      mysterious and are debatable because we have yet to define the molecules that
      participate in these processes. We are interested in identifying the existence of
      expressed genes, or mRNA species, that are specifically associated with
      circulating cells of cancer-bearing patients using prostate cancer (PCa) as a
      model. RESULTS: We established two comprehensive subtracted cDNA libraries using
      a molecular technique called suppression subtractive hybridization. This
      technique selectively amplifies transcripts that are specifically expressed in
      circulating cells of either PCa patients or healthy men. Following sequencing
      reaction, we showed that 17 out of 23 (73.9%) sequenced clones did not match any
      mRNAs in the GenBank database. This result suggests that genes associated with
      alterations in circulating cells of cancer-bearing patients are largely unknown.
      Semi-quantitative RT-PCR confirmed that two genes are up-regulated in circulating
      cells of PCa patients, whereas another two genes are down-regulated in the same
      patients. CONCLUSION: The comprehensive gene expression analysis is capable of
      identifying differentially expressed genes in circulating cells of healthy men
      and PCa patients. We did not attempt to enrich specific cell types in this study
      because phenotypes of CTCs and subsets of leukocytes participating in
      immunosurveillance remain largely unknown. Continuous studies of these
      differentially expressed genes will eventually lead us to understand the
      mechanisms involved in tumor metastasis and immune modulation during cancer
      development.

PMID- 16086836
TI  - High frequency of the IVS2-2A>G DNA sequence variation in SLC26A5, encoding the
      cochlear motor protein prestin, precludes its involvement in hereditary hearing
      loss.
AB  - BACKGROUND: Cochlear outer hair cells change their length in response to
      variations in membrane potential. This capability, called electromotility, is
      believed to enable the sensitivity and frequency selectivity of the mammalian
      cochlea. Prestin is a transmembrane protein required for electromotility.
      Homozygous prestin knockout mice are profoundly hearing impaired. In humans, a
      single nucleotide change in SLC26A5, encoding prestin, has been reported in
      association with hearing loss. This DNA sequence variation, IVS2-2A>G, occurs in
      the exon 3 splice acceptor site and is expected to abolish splicing of exon 3.
      METHODS: To further explore the relationship between hearing loss and the IVS2
      2A>G transition, and assess allele frequency, genomic DNA from hearing impaired
      and control subjects was analyzed by DNA sequencing. SLC26A5 genomic DNA
      sequences from human, chimp, rat, mouse, zebrafish and fruit fly were aligned and
      compared for evolutionary conservation of the exon 3 splice acceptor site.
      Alternative splice acceptor sites within intron 2 of human SLC26A5 were sought
      using a splice site prediction program from the Berkeley Drosophila Genome
      Project. RESULTS: The IVS2-2A>G variant was found in a heterozygous state in 4 of
      74 hearing impaired subjects of Hispanic, Caucasian or uncertain ethnicity and 4
      of 150 Hispanic or Caucasian controls (p = 0.45). The IVS2-2A>G variant was not
      found in 106 subjects of Asian or African American descent. No homozygous
      subjects were identified (n = 330). Sequence alignment of SLC26A5 orthologs
      demonstrated that the A nucleotide at position IVS2-2 is invariant among several
      eukaryotic species. Sequence analysis also revealed five potential alternative
      splice acceptor sites in intron 2 of human SLC26A5. CONCLUSION: These data
      suggest that the IVS2-2A>G variant may not occur more frequently in hearing
      impaired subjects than in controls. The identification of five potential
      alternative splice acceptor sites in intron 2 of human SLC26A5 suggests a
      potential mechanism by which expression of prestin might be maintained in cells
      carrying the SLC26A5 IVS2-2A>G DNA sequence variation. Additional studies are
      needed to evaluate the effect of the IVS2-2A>G transition on splicing of SLC26A5
      transcripts and characterize the hearing status of individuals homozygous for the
      IVS2-2A>G variant.

PMID- 16086837
TI  - The tissue micro-array data exchange specification: a web based experience
      browsing imported data.
AB  - BACKGROUND: The AIDS and Cancer Specimen Resource (ACSR) is an HIV/AIDS tissue
      bank consortium sponsored by the National Cancer Institute (NCI) Division of
      Cancer Treatment and Diagnosis (DCTD). The ACSR offers to approved researchers
      HIV infected biologic samples and uninfected control tissues including tissue
      cores in micro-arrays (TMA) accompanied by de-identified clinical data.
      Researchers interested in the type and quality of TMA tissue cores and the
      associated clinical data need an efficient method for viewing available TMA
      materials. Because each of the tissue samples within a TMA has separate data
      including a core tissue digital image and clinical data, an organized, standard
      approach to producing, navigating and publishing such data is necessary. The
      Association for Pathology Informatics (API) extensible mark-up language (XML) TMA
      data exchange specification (TMA DES) proposed in April 2003 provides a common
      format for TMA data. Exporting TMA data into the proposed format offers an
      opportunity to implement the API TMA DES. Using our public BrowseTMA tool, we
      created a web site that organizes and cross references TMA lists, digital
      "virtual slide" images, TMA DES export data, linked legends and clinical details
      for researchers. Microsoft Excel and Microsoft Word are used to convert tabular
      clinical data and produce an XML file in the TMA DES format. The BrowseTMA tool
      contains Extensible Stylesheet Language Transformation (XSLT) scripts that
      convert XML data into Hyper-Text Mark-up Language (HTML) web pages with
      hyperlinks automatically added to allow rapid navigation. RESULTS: Block lists,
      virtual slide images, legends, clinical details and exports have been placed on
      the ACSR web site for 14 blocks with 1623 cores of 2.0, 1.0 and 0.6 mm sizes. Our
      virtual microscope can be used to view and annotate these TMA images. Researchers
      can readily navigate from TMA block lists to TMA legends and to clinical details
      for a selected tissue core. Exports for 11 blocks with 3812 cores from three
      other institutions were processed with the BrowseTMA tool. Fifty common data
      elements (CDE) from the TMA DES were used and 42 more created for site-specific
      data. Researchers can download TMA clinical data in the TMA DES format.
      CONCLUSION: Virtual TMAs with clinical data can be viewed on the Internet by
      interested researchers using the BrowseTMA tool. We have organized our approach
      to producing, sorting, navigating and publishing TMA information to facilitate
      such review. We have converted Excel TMA data into TMA DES XML, and imported it
      and TMA DES XML from another institution into BrowseTMA to produce web pages that
      allow us to browse through the merged data. We proposed enhancements to the TMA
      DES as a result of this experience. We implemented improvements to the API TMA
      DES as a result of using exported data from several institutions. A document type
      definition was written for the API TMA DES (that optionally includes proposed
      enhancements). Independent validators can be used to check exports against the
      DTD (with or without the proposed enhancements). Linking tissue core images to
      readily navigable clinical data greatly improves the value of the TMA.

PMID- 16086838
TI  - Repeated high doses of avermectins cause prolonged sterilisation, but do not
      kill, Onchocerca ochengi adult worms in African cattle.
AB  - BACKGROUND: Ivermectin (Mectizan, Merck and CO. Inc.) is being widely used in the
      control of human onchocerciasis (Onchoverca volvulus) because of its potent
      effect on microfilariae. Human studies have suggested that, at the standard dose
      of 150 microg/kg an annual treatment schedule of ivermectin reversibly interferes
      with female worm fertility but is not macrofilaricidal. Because of the importance
      of determining whether ivermectin could be macrofilaricidal, the efficacy of high
      and prolonged doses of ivermectin and a related avermectin, doramectin, were
      investigated in cattle infected with O. ochengi. METHODS: Drugs with potential
      macrofilaricidal activity, were screened for the treatment of human
      onchocerciasis, using natural infections of O. ochengi in African cattle. Three
      groups of 3 cows were either treated at monthly intervals (7 treatments) with
      ivermectin (Ivomec, Merck and Co. Inc.) at 500 microg/kg or doramectin (Dectamax,
      Pfizer) at 500 microg/kg or not treated as controls. Intradermal nodules were
      removed at 6 monthly intervals and adult worms were examined for signs of drug
      activity. RESULTS: There was no significant decline in nodule diameter, the
      motility of male and female worms, nor in male and female viability as determined
      by the ability to reduce tetrazolium, compared with controls, at any time up to
      24 months from the start of treatments (mpt). Embryogenesis, however, was
      abrogated by treatment, which was seen as an accumulation of dead and dying intra
      uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in
      treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf
      were found in the skin of some treated animals and a few female worms were
      starting to produce multi-cellular embryonic stages. Follow-up of the doramectin
      treated group at 36 mpt showed that mf densities had still only regained a small
      proportion of their pre-treatment levels. CONCLUSION: These results have
      important implications for onchocerciasis control in the field. They suggest that
      ivermectin given at repeated high does may sterilise O. volvulus female worms for
      prolonged periods but is unlikely to kill them. This supports the view that
      control programmes may need to continue treatments with ivermectin for a period
      of decades and highlights the need to urgently identify new marcofiliaricidal
      compounds.

PMID- 16086839
TI  - Treatment of osteoarthritis of the knee with a topical diclofenac solution: a
      randomised controlled, 6-week trial [ISRCTN53366886].
AB  - BACKGROUND: Topical NSAIDs have been proven to relieve the symptoms of
      osteoarthritis (OA) in short-term studies (2 weeks). To justify its chronic use,
      efficacy of a topical NSAID over a longer term of study should be demonstrated.
      The efficacy and safety of a topical diclofenac solution over a 6-week treatment
      course in symptomatic primary OA of the knee was investigated. METHODS: 216 men
      and women, age 40-85 years, with radiologically confirmed primary OA of the knee
      and a flare of pain at baseline following discontinuation of prior therapy were
      enrolled into this double-blind study. Participants applied either a topical
      diclofenac solution (Pennsaid) or vehicle control solution (carrier with no
      diclofenac); 40 drops 4 times daily directly to the painful knee(s), without
      massage, for 6 weeks. Pre-planned primary efficacy outcome measures included the
      core continuous variables pain relief and improved physical function measured by
      the Western Ontario and McMaster Universities (WOMAC) LK3.1 OA Index, and
      improved patient global assessment (PGA). Secondary efficacy measure was reduced
      stiffness. Safety assessments included adverse events and vital signs. RESULTS:
      The topical diclofenac group had a significantly greater mean change in score
      (final minus baseline) compared to the vehicle control group for pain (-5.2 vs. 
      3.3, p = 0.003), physical function (-13.4 vs. -6.9, p = 0.001), PGA (-1.3 vs. 
      0.7, p = 0.0001) and stiffness (-1.8 vs. -0.9, p = 0.002). The mean difference
      between treatment arms (95% confidence interval [CI]) was 1.9 (0.7 to 3.2), 6.5
      (2.5 to 10.5), 0.6 (0.2 to 0.9), and 0.9 (0.3 to 1.4), respectively. Safety
      analyses showed that topical diclofenac caused skin irritation, mostly minor
      local skin dryness, in 42/107 (39%), leading to discontinuation of treatment in
      5/107 (5%) participants. CONCLUSION: This topical diclofenac solution
      demonstrated relief at 6 weeks of the symptoms of primary osteoarthritis of the
      knee.

PMID- 16086840
TI  - Expression of transforming growth factor-beta-1 and p27Kip1 in pancreatic
      adenocarcinomas: relation with cell-cycle-associated proteins and
      clinicopathologic characteristics.
AB  - BACKGROUND: The purpose of our study was to investigate the immunohistochemical
      expression of TGF-beta1 and p27 in pancreatic adenocarcinomas and to compare the
      findings with the clinicopathological features and survival. We also aimed to
      evaluate the expression of TGF-beta1 and p27 in the context of other cell cycle
      and proliferation markers such as cyclin D1 and Ki-67. METHODS: We examined TGF
      beta1 and p27 expression immunohistochemically in 63 cases of invasive ductal
      adenocarcinoma of the pancreas. Standard streptavidin-biotin immunperoxidase
      method was used for immunostaining and the stained slides were examined
      microscopically using semiquantitative criteria. RESULTS: TGF-beta1 stained the
      cytoplasms of the tumor cells in 43 cases [68.3%]. There was a statistically
      significant difference among TGF-beta1 staining scores in terms of
      clinicopathologic factors such as blood vessel invasion, stage and distant
      metastasis [p < 0.05]. Of the 63 tumors evaluated 23 [36.5%] were positive for
      p27 within the nucleus. An inverse correlation was found between p27
      immunoreactivity and grade [p < 0.05]. But no significant correlation was found
      between p27 and other parameters. Among the patients with survival data 27
      patients had RO resections and these cases were considered in survival analysis.
      In the univariate analysis, neither TGF-beta1 nor p27 expression was related with
      patient survival. CONCLUSION: Our findings suggest that in pancreatic carcinoma,
      TGF-beta1 expression is related to tumor growth and metastasis. But it is not
      associated with cell cycle proteins. p27 expression is reduced in pancreatic
      adenocarcinomas and decreased protein levels of p27 may play a role in the
      differentiation of pancreatic cancer.

PMID- 16086841
TI  - Genomic multiple sequence alignments: refinement using a genetic algorithm.
AB  - BACKGROUND: Genomic sequence data cannot be fully appreciated in isolation.
      Comparative genomics--the practice of comparing genomic sequences from different
      species--plays an increasingly important role in understanding the genotypic
      differences between species that result in phenotypic differences as well as in
      revealing patterns of evolutionary relationships. One of the major challenges in
      comparative genomics is producing a high-quality alignment between two or more
      related genomic sequences. In recent years, a number of tools have been developed
      for aligning large genomic sequences. Most utilize heuristic strategies to
      identify a series of strong sequence similarities, which are then used as anchors
      to align the regions between the anchor points. The resulting alignment is
      globally correct, but in many cases is suboptimal locally. We describe a new
      program, GenAlignRefine, which improves the overall quality of global multiple
      alignments by using a genetic algorithm to improve local regions of alignment.
      Regions of low quality are identified, realigned using the program T-Coffee, and
      then refined using a genetic algorithm. Because a better COFFEE (Consistency
      based Objective Function For alignmEnt Evaluation) score generally reflects
      greater alignment quality, the algorithm searches for an alignment that yields a
      better COFFEE score. To improve the intrinsic slowness of the genetic algorithm,
      GenAlignRefine was implemented as a parallel, cluster-based program. RESULTS: We
      tested the GenAlignRefine algorithm by running it on a Linux cluster to refine
      sequences from a simulation, as well as refine a multiple alignment of 15
      Orthopoxvirus genomic sequences approximately 260,000 nucleotides in length that
      initially had been aligned by Multi-LAGAN. It took approximately 150 minutes for
      a 40-processor Linux cluster to optimize some 200 fuzzy (poorly aligned) regions
      of the orthopoxvirus alignment. Overall sequence identity increased only
      slightly; but significantly, this occurred at the same time that the overall
      alignment length decreased--through the removal of gaps--by approximately 200
      gapped regions representing roughly 1,300 gaps. CONCLUSION: We have implemented a
      genetic algorithm in parallel mode to optimize multiple genomic sequence
      alignments initially generated by various alignment tools. Benchmarking
      experiments showed that the refinement algorithm improved genomic sequence
      alignments within a reasonable period of time.

PMID- 16086842
TI  - A quest for therapeutic antigens in bone and soft tissue sarcoma.
AB  - Over the past three decades, there have been remarkable advances in the treatment
      of bone and soft tissue sarcomas. These include the introduction of adjuvant
      chemotherapy, establishment of guidelines for adequate surgical margins, and the
      development of post-excision reconstruction. There have also been advances in the
      field of immunotherapy against bone and soft tissue sarcomas, which,
      unfortunately, have received less attention. However, lack of progress in
      chemotherapy-based treatments for bone and soft tissue sarcomas has reignited
      interest in immunotherapeutic approaches. Here we summarize current progress in
      the immunotherapy of bone and soft tissue sarcomas including the strategies
      utilized to identify tumor-associated antigens, and the design of clinical
      trials.

PMID- 16086843
TI  - Attention demanding tasks during treadmill walking reduce step width variability
      in young adults.
AB  - BACKGROUND: The variability of step time and step width is associated with falls
      by older adults. Further, step time is significantly influenced when performing
      attention demanding tasks while walking. Without exception, step time variability
      has been reported to increase in normal and pathologically aging older adults.
      Because of the role of step width in managing frontal plane dynamic stability,
      documenting the influence of attention-demanding tasks on step width variability
      may provide insight to events that can disturb dynamic stability during
      locomotion and increase fall risk. Preliminary evidence suggests performance of
      an attention demanding task significantly decreases step width variability of
      young adults walking on a treadmill. The purpose of the present study was to
      confirm or refute this finding by characterizing the extent and direction of the
      effects of a widely used attention demanding task (Stroop test) on the step width
      variability of young adults walking on a motorized treadmill. METHODS: Fifteen
      healthy young adults walked on a motorized treadmill at a self-selected velocity
      for 10 minutes under two conditions; without performing an attention demanding
      task and while performing the Stroop test. Step width of continuous and
      consecutive steps during the collection was derived from the data recorded using
      a motion capture system. Step width variability was computed as the standard
      deviation of all recorded steps. RESULTS: Step width decreased four percent
      during performance of the Stroop test but the effect was not significant (p =
      0.10). In contrast, the 16 percent decrease in step width variability during the
      Stroop test condition was significant (p = 0.029). CONCLUSION: The results
      support those of our previous work in which a different attention demanding task
      also decreased step width variability of young subjects while walking on a
      treadmill. The decreased step width variability observed while performing an
      attention demanding task during treadmill walking may reflect a voluntary gait
      adaptation toward a more conservative gait pattern emphasizing frontal plane
      control of the trunk. Extension of the experimental paradigm to older adults and
      mechanistic approaches to link step width variability to dynamic stability, and
      falls, in a cause-effect manner are necessary.

PMID- 16086845
TI  - Physiology engages with functional genomics - at last.
AB  - A report on the XXXV International Congress of Physiological Sciences, held
      together with Experimental Biology 2005, San Diego, USA, 31 March - 6 April 2005.

PMID- 16086844
TI  - Endothelial cell injury by high glucose and heparanase is prevented by insulin,
      heparin and basic fibroblast growth factor.
AB  - BACKGROUND: Uncontrolled hyperglycemia is the main risk factor in the development
      of diabetic vascular complications. The endothelial cells are the first cells
      targeted by hyperglycemia. The mechanism of endothelial injury by high glucose is
      still poorly understood. Heparanase production, induced by hyperglycemia, and
      subsequent degradation of heparan sulfate may contribute to endothelial injury.
      Little is known about endothelial injury by heparanase and possible means of
      preventing this injury. OBJECTIVES: To determine if high glucose as well as
      heparanase cause endothelial cell injury and if insulin, heparin and bFGF protect
      cells from this injury. METHODS: Cultured porcine aortic endothelial cells were
      treated with high glucose (30 mM) and/or insulin (1 U/ml) and/or heparin (0.5
      microg/ml) and /or basic fibroblast growth factor (bFGF) (1 ng/ml) for seven
      days. Cells were also treated with heparinase I (0.3 U/ml, the in vitro surrogate
      heparanase), plus insulin, heparin and bFGF for two days in serum free medium.
      Endothelial cell injury was evaluated by determining the number of live cells per
      culture and lactate dehydrogenase (LDH) release into medium expressed as
      percentage of control. RESULTS: A significant decrease in live cell number and
      increase in LDH release was found in endothelial cells treated with high glucose
      or heparinase I. Insulin and/or heparin and/or bFGF prevented these changes and
      thus protected cells from injury by high glucose or heparinase I. The protective
      ability of heparin and bFGF alone or in combination was more evident in cells
      damaged with heparinase I than high glucose. CONCLUSION: Endothelial cells
      injured by high glucose or heparinase I are protected by a combination of
      insulin, heparin and bFGF, although protection by heparin and/or bFGF was
      variable.

PMID- 16086846
TI  - Genomic mapping of RNA polymerase II reveals sites of co-transcriptional
      regulation in human cells.
AB  - BACKGROUND: Transcription by RNA polymerase II is regulated at many steps
      including initiation, promoter release, elongation and termination. Accumulation
      of RNA polymerase II at particular locations across genes can be indicative of
      sites of regulation. RNA polymerase II is thought to accumulate at the promoter
      and at sites of co-transcriptional alternative splicing where the rate of RNA
      synthesis slows. RESULTS: To further understand transcriptional regulation at a
      global level, we determined the distribution of RNA polymerase II within regions
      of the human genome designated by the ENCODE project. Hypophosphorylated RNA
      polymerase II localizes almost exclusively to 5' ends of genes. On the other
      hand, localization of total RNA polymerase II reveals a variety of distinct
      landscapes across many genes with 74% of the observed enriched locations at
      exons. RNA polymerase II accumulates at many annotated constitutively spliced
      exons, but is biased for alternatively spliced exons. Finally, RNA polymerase II
      is also observed at locations not in gene regions. CONCLUSION: Localizing RNA
      polymerase II across many millions of base pairs in the human genome identifies
      novel sites of transcription and provides insights into the regulation of
      transcription elongation. These data indicate that RNA polymerase II accumulates
      most often at exons during transcription. Thus, a major factor of transcription
      elongation control in mammalian cells is the coordination of transcription and
      pre-mRNA processing to define exons.

PMID- 16086847
TI  - The molecular portrait of in vitro growth by meta-analysis of gene-expression
      profiles.
AB  - BACKGROUND: Cell lines as model systems of tumors and tissues are essential in
      molecular biology, although they only approximate the properties of in vivo cells
      in tissues. Cell lines have been selected under in vitro conditions for a long
      period of time, affecting many specific cellular pathways and processes. RESULTS:
      To identify the transcriptional changes caused by long term in vitro selection,
      we performed a gene-expression meta-analysis and compared 60 tumor cell lines (of
      nine tissue origins) to 135 human tissue and 176 tumor tissue samples. Using
      significance analysis of microarrays we demonstrated that cell lines showed
      statistically significant differential expression of approximately 30% of the
      approximately 7,000 genes investigated compared to the tissues. Most of the
      differences were associated with the higher proliferation rate and the disrupted
      tissue organization in vitro. Thus, genes involved in cell-cycle progression,
      macromolecule processing and turnover, and energy metabolism were upregulated in
      cell lines, whereas cell adhesion molecules and membrane signaling proteins were
      downregulated. CONCLUSION: Detailed molecular understanding of how cells adapt to
      the in vitro environment is important, as it will both increase our understanding
      of tissue organization and result in a refined molecular portrait of
      proliferation. It will further indicate when to use immortalized cell lines, or
      when it is necessary to instead use three-dimensional cultures, primary cell
      cultures or tissue biopsies.

PMID- 16086848
TI  - Evolution of selenium utilization traits.
AB  - BACKGROUND: The essential trace element selenium is used in a wide variety of
      biological processes. Selenocysteine (Sec), the 21st amino acid, is co
      translationally incorporated into a restricted set of proteins. It is encoded by
      an UGA codon with the help of tRNASec (SelC), Sec-specific elongation factor
      (SelB) and a cis-acting mRNA structure (SECIS element). In addition, Sec synthase
      (SelA) and selenophosphate synthetase (SelD) are involved in the biosynthesis of
      Sec on the tRNASec. Selenium is also found in the form of 2-selenouridine, a
      modified base present in the wobble position of certain tRNAs, whose synthesis is
      catalyzed by YbbB using selenophosphate as a precursor. RESULTS: We analyzed
      completely sequenced genomes for occurrence of the selA, B, C, D and ybbB genes.
      We found that selB and selC are gene signatures for the Sec-decoding trait.
      However, selD is also present in organisms that do not utilize Sec, and shows
      association with either selA, B, C and/or ybbB. Thus, selD defines the overall
      selenium utilization. A global species map of Sec-decoding and 2-selenouridine
      synthesis traits is provided based on the presence/absence pattern of selenium
      utilization genes. The phylogenies of these genes were inferred and compared to
      organismal phylogenies, which identified horizontal gene transfer (HGT) events
      involving both traits. CONCLUSION: These results provide evidence for the ancient
      origin of these traits, their independent maintenance, and a highly dynamic
      evolutionary process that can be explained as the result of speciation,
      differential gene loss and HGT. The latter demonstrated that the loss of these
      traits is not irreversible as previously thought.

PMID- 16086849
TI  - Patterns of intron sequence evolution in Drosophila are dependent upon length and
      GC content.
AB  - BACKGROUND: Introns comprise a large fraction of eukaryotic genomes, yet little
      is known about their functional significance. Regulatory elements have been
      mapped to some introns, though these are believed to account for only a small
      fraction of genome wide intronic DNA. No consistent patterns have emerged from
      studies that have investigated general levels of evolutionary constraint in
      introns. RESULTS: We examine the relationship between intron length and levels of
      evolutionary constraint by analyzing inter-specific divergence at 225 intron
      fragments in Drosophila melanogaster and Drosophila simulans, sampled from a
      broad distribution of intron lengths. We document a strongly negative correlation
      between intron length and divergence. Interestingly, we also find that divergence
      in introns is negatively correlated with GC content. This relationship does not
      account for the correlation between intron length and divergence, however, and
      may simply reflect local variation in mutational rates or biases. CONCLUSION:
      Short introns make up only a small fraction of total intronic DNA in the genome.
      Our finding that long introns evolve more slowly than average implies that, while
      the majority of introns in the Drosophila genome may experience little or no
      selective constraint, most intronic DNA in the genome is likely to be evolving
      under considerable constraint. Our results suggest that functional elements may
      be ubiquitous within longer introns and that these introns may have a more
      general role in regulating gene expression than previously appreciated. Our
      finding that GC content and divergence are negatively correlated in introns has
      important implications for the interpretation of the correlation between
      divergence and levels of codon bias observed in Drosophila.

PMID- 16086850
TI  - The Dictyostelium genome encodes numerous RasGEFs with multiple biological roles.
AB  - BACKGROUND: Dictyostelium discoideum is a eukaryote with a simple lifestyle and a
      relatively small genome whose sequence has been fully determined. It is widely
      used for studies on cell signaling, movement and multicellular development. Ras
      guanine-nucleotide exchange factors (RasGEFs) are the proteins that activate Ras
      and thus lie near the top of many signaling pathways. They are particularly
      important for signaling in development and chemotaxis in many organisms,
      including Dictyostelium. RESULTS: We have searched the genome for sequences
      encoding RasGEFs. Despite its relative simplicity, we find that the Dictyostelium
      genome encodes at least 25 RasGEFs, with a few other genes encoding only parts of
      the RasGEF consensus domains. All appear to be expressed at some point in
      development. The 25 genes include a wide variety of domain structures, most of
      which have not been seen in other organisms. The LisH domain, which is associated
      with microtubule binding, is seen particularly frequently; other domains that
      confer interactions with the cytoskeleton are also common. Disruption of a sample
      of the novel genes reveals that many have clear phenotypes, including altered
      morphology and defects in chemotaxis, slug phototaxis and thermotaxis.
      CONCLUSION: These results suggest that the unexpectedly large number of RasGEF
      genes reflects an evolutionary expansion of the range of Ras signaling rather
      than functional redundancy or the presence of multiple pseudogenes.

PMID- 16086851
TI  - Tandem repeat copy-number variation in protein-coding regions of human genes.
AB  - BACKGROUND: Tandem repeat variation in protein-coding regions will alter protein
      length and may introduce frameshifts. Tandem repeat variants are associated with
      variation in pathogenicity in bacteria and with human disease. We characterized
      tandem repeat polymorphism in human proteins, using the UniGene database, and
      tested whether these were associated with host defense roles. RESULTS: Protein
      coding tandem repeat copy-number polymorphisms were detected in 249 tandem
      repeats found in 218 UniGene clusters; observed length differences ranged from 2
      to 144 nucleotides, with unit copy lengths ranging from 2 to 57. This
      corresponded to 1.59% (218/13,749) of proteins investigated carrying detectable
      polymorphisms in the copy-number of protein-coding tandem repeats. We found no
      evidence that tandem repeat copy-number polymorphism was significantly elevated
      in defense-response proteins (p = 0.882). An association with the Gene Ontology
      term 'protein-binding' remained significant after covariate adjustment and
      correction for multiple testing. Combining this analysis with previous
      experimental evaluations of tandem repeat polymorphism, we estimate the
      approximate mean frequency of tandem repeat polymorphisms in human proteins to be
      6%. Because 13.9% of the polymorphisms were not a multiple of three nucleotides,
      up to 1% of proteins may contain frameshifting tandem repeat polymorphisms.
      CONCLUSION: Around 1 in 20 human proteins are likely to contain tandem repeat
      copy-number polymorphisms within coding regions. Such polymorphisms are not more
      frequent among defense-response proteins; their prevalence among protein-binding
      proteins may reflect lower selective constraints on their structural
      modification. The impact of frameshifting and longer copy-number variants on
      protein function and disease merits further investigation.

PMID- 16086852
TI  - Evidence for a second class of S-adenosylmethionine riboswitches and other
      regulatory RNA motifs in alpha-proteobacteria.
AB  - BACKGROUND: Riboswitches are RNA elements in the 5' untranslated leaders of
      bacterial mRNAs that directly sense the levels of specific metabolites with a
      structurally conserved aptamer domain to regulate expression of downstream genes.
      Riboswitches are most common in the genomes of low GC Gram-positive bacteria (for
      example, Bacillus subtilis contains examples of all known riboswitches), and some
      riboswitch classes seem to be restricted to this group. RESULTS: We used
      comparative sequence analysis and structural probing to identify five RNA
      elements (serC, speF, suhB, ybhL, and metA) that reside in the intergenic regions
      of Agrobacterium tumefaciens and many other alpha-proteobacteria. One of these,
      the metA motif, is found upstream of methionine biosynthesis genes and binds S
      adenosylmethionine (SAM). This natural aptamer most likely functions as a SAM
      riboswitch (SAM-II) with a consensus sequence and structure that is distinct from
      the class of SAM riboswitches (SAM-I) predominantly found in Gram-positive
      bacteria. The minimal functional SAM-II aptamer consists of fewer than 70
      nucleotides, which form a single stem and a pseudoknot. Despite its simple
      architecture and lower affinity for SAM, the SAM-II aptamer strongly
      discriminates against related compounds. CONCLUSION: SAM-II is the only
      metabolite-binding riboswitch class identified so far that is not found in Gram
      positive bacteria, and its existence demonstrates that biological systems can use
      multiple RNA structures to sense a single chemical compound. The two SAM
      riboswitches might be 'RNA World' relics that were selectively retained in
      certain bacterial lineages or new motifs that have emerged since the divergence
      of the major bacterial groups.

PMID- 16086853
TI  - MicroRNA profiling of the murine hematopoietic system.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of recently discovered noncoding RNA
      genes that post-transcriptionally regulate gene expression. It is becoming clear
      that miRNAs play an important role in the regulation of gene expression during
      development. However, in mammals, expression data are principally based on whole
      tissue analysis and are still very incomplete. RESULTS: We used oligonucleotide
      arrays to analyze miRNA expression in the murine hematopoietic system.
      Complementary oligonucleotides capable of hybridizing to 181 miRNAs were
      immobilized on a membrane and probed with radiolabeled RNA derived from low
      molecular weight fractions of total RNA from several different hematopoietic and
      neuronal cells. This method allowed us to analyze cell type-specific patterns of
      miRNA expression and to identify miRNAs that might be important for cell lineage
      specification and/or cell effector functions. CONCLUSION: This is the first
      report of systematic miRNA gene profiling in cells of the hematopoietic system.
      As expected, miRNA expression patterns were very different between hematopoietic
      and non-hematopoietic cells, with further subtle differences observed within the
      hematopoietic group. Interestingly, the most pronounced similarities were
      observed among fully differentiated effector cells (Th1 and Th2 lymphocytes and
      mast cells) and precursors at comparable stages of differentiation (double
      negative thymocytes and pro-B cells), suggesting that in addition to regulating
      the process of commitment to particular cellular lineages, miRNAs might have an
      important general role in the mechanism of cell differentiation and maintenance
      of cell identity.

PMID- 16086855
TI  - The life aquatic.
AB  - If we want to know for sure whether there was, or still is, life on Mars, we have
      to send people there.

PMID- 16086854
TI  - Genome-wide promoter extraction and analysis in human, mouse, and rat.
AB  - Large-scale and high-throughput genomics research needs reliable and
      comprehensive genome-wide promoter annotation resources. We have conducted a
      systematic investigation on how to improve mammalian promoter prediction by
      incorporating both transcript and conservation information. This enabled us to
      build a better multispecies promoter annotation pipeline and hence to create
      CSHLmpd (Cold Spring Harbor Laboratory Mammalian Promoter Database) for the
      biomedical research community, which can act as a starting reference system for
      more refined functional annotations.

PMID- 16086856
TI  - Datasets for evolutionary comparative genomics.
AB  - Many decisions about genome sequencing projects are directed by perceived gaps in
      the tree of life, or towards model organisms. With the goal of a better
      understanding of biology through the lens of evolution, however, there are
      additional genomes that are worth sequencing. One such rationale for whole-genome
      sequencing is discussed here, along with other important strategies for
      understanding the phenotypic divergence of species.

PMID- 16086857
TI  - The SET-domain protein superfamily: protein lysine methyltransferases.
AB  - The SET-domain protein methyltransferase superfamily includes all but one of the
      proteins known to methylate histones on lysine. Histone methylation is important
      in the regulation of chromatin and gene expression.

PMID- 16086858
TI  - Cytological profiling: providing more haystacks for chemists' needles.
AB  - Conventional high-throughput 'chemical genetic' screening seeks to identify small
      molecule inhibitors of a specific protein or pathway. A recent study describes
      how unbiased screening of cellular morphology, followed by affinity purification
      to identify targets of compounds with interesting effects, can lead to the
      identification of novel inhibitors.

PMID- 16086859
TI  - Metagenomics for studying unculturable microorganisms: cutting the Gordian knot.
AB  - More than 99% of prokaryotes in the environment cannot be cultured in the
      laboratory, a phenomenon that limits our understanding of microbial physiology,
      genetics, and community ecology. One way around this problem is metagenomics, the
      culture-independent cloning and analysis of microbial DNA extracted directly from
      an environmental sample. Recent advances in shotgun sequencing and computational
      methods for genome assembly have advanced the field of metagenomics to provide
      glimpses into the life of uncultured microorganisms.

PMID- 16086860
TI  - Fungal biology reaps the benefit of genomics.
AB  - A report on the 23rd Fungal Genetics Conference, Pacific Grove, USA, 15-20 March
      2005.

PMID- 16086861
TI  - Human genome research enters a new phase.
AB  - A report on HGM2005, the tenth annual Human Genome Meeting, Kyoto, Japan, 18-21
      April 2005.

PMID- 16086862
TI  - Systems biology: where it's at in 2005.
AB  - A report on the joint Keystone Symposia on Systems and Biology and Proteomics and
      Bioinformatics, Keystone, USA, 8-13 April 2005.

PMID- 16086864
TI  - [Herpes simplex virus type 1 thymidine kinase/ganciclovir (HSV(1)-TK/GCV) system
      as an effective "in vivo death switch" of live tumor vaccines].
AB  - BACKGROUND & OBJECTIVE: Live tumor vaccines could achieve better
      immunotherapeutic effects than irradiated tumor vaccines; however, the
      tumorigenicity is the crucial drawback incurred by the current procedures for
      vaccine preparation. This study was to explore the application of herpes simplex
      virus type 1 thymidine kinase/ganciclovir (HSV1-TK/GCV) system as "in vivo death
      switch" to control the survival status of cancer vaccines under certain
      circumstances. METHODS: Suicide gene HSV(1)-TK was transferred into ovarian
      cancer cell line NuTu-19 with a retrovirus vector, followed by G418 selection to
      obtain HSV(1)-TK-transfected NuTu-19 cells (NuTu-19/TK). Dendritic cells (DCs)
      derived from Fischer344 rat bone marrow were fused with NuTu-19/TK cells to
      construct live tumor vaccine FC/TK. The expression of HSV(1)-TK in FC/TK cells
      was determined by reverse transcription-polymerase chain reaction (RT-PCR) and
      Western blot. The cytotoxic efficacy of GCV on FC/TK cells was evaluated by XTT
      assay. The apoptosis of FC/TK cells was analyzed by flow cytometry and
      Hoechst33258 staining after GCV treatment. Rats were vaccinated with FC/TK cells
      and divided into 2 groups: GCV group (5 rats) were intraperitoneally treated with
      GCV for 7 days, control group (5 rats) were treated with normal saline. The
      tumorigenesis and tumor metastasis in the rats were observed 90 days after
      inoculation. RESULTS: HSV1-TK was specifically expressed in FC/TK cells. GCV
      showed in vitro cytotoxicity to FC/TK cells in a dose-dependent manner, and
      86.25% of the FC/TK cells were killed by GCV at a concentration of 100 microg/ml;
      the apoptosis rate of FC/TK cells was over 80%, and apoptotic morphology,
      including cell shrinkage, chromatin condensation, was observed. In the rat
      models, the tumor was developed at the injection site in 3 rats of control group,
      while no tumor was observed in the rats of GCV group. CONCLUSION: HSV(1)-TK/GCV
      could act as the "death switch" of tumor vaccines by triggering apoptosis of
      tumor vaccines both in vitro and in vivo.

PMID- 16086865
TI  - [Correlation of polymeric immunoglobulin receptor gene polymorphisms to
      susceptibility of nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Polymeric immunoglobulin receptor (pIgR) gene plays a
      central role in immune response, and is closely related to Epstein-Barr virus
      (EBV) infection. Therefore, it is an ideal candidate gene for research on genetic
      susceptibility of nasopharyngeal carcinoma (NPC). This study was designed to
      explore correlation of pIgR gene polymorphisms to genetic susceptibility of NPC.
      METHODS: Four single nucleotide polymorphisms (SNPs) within the exon regions of
      pIgR were detected by polymerase chain reaction (PCR); pIgR was genotyped in 528
      NPC patients and 408 healthy individuals in the Cantonese population to analyze
      frequencies of its allelic genes. RESULTS: Differences in frequencies of the 4
      SNPs between NPC patients and healthy controls were not significant (P > 0.05).
      All subjects were categorized into 2 groups by age of 45uof the subjects in age
      of < or =45 group, the frequency of minor allele T of SNP C8880T was
      significantly higher in NPC patients than in healthy controls (7% vs. 4%, P <
      0.05). Individuals carried allele T suffered higher risk of NPC (odds
      ratio=1.84). CONCLUSION: SNP C8880T of pIgR is related with NPC susceptibility;
      pIgR gene may be associated to risk of NPC development.

PMID- 16086866
TI  - [Epidermal growth factor receptor mutation in Chinese patients with non-small
      cell lung cancer].
AB  - BACKGROUND & OBJECTIVE: Recent studies showed that somatic mutations in epidermal
      growth factor receptor (EGFR) tyrosine kinase (TK) domain are associated with
      sensitivity of non-small cell lung cancer(NSCLC) to TK inhibitor gefitinib. The
      mutations, including in-frame deletions at exon 19 and substitutions at exon 18
      or exon 21, cluster around ATP-binding pocket of TK domain. The frequency of
      mutations are higher in Japanese patients than in American patients. This study
      was to analyze EGFR mutations in Chinese patients with NSCLC. METHODS: From Jun.
      to Oct. 2004, fresh specimens of lung cancer and corresponding normal lung tissue
      were collected from 52 consecutive NSCLC patients (39 men and 13 women) treated
      in Cancer Center of Sun Yat-sen University. All patients had not received
      treatment of gefitinib. DNA was extracted from the 52 specimens. Exons 19 and 21
      were amplified by polymerase chain reaction (PCR), and sequenced and analyzed
      from both sense and antisense directions. RESULTS: Somatic mutations in TK domain
      of EGFR in tumors were identified from 10 of the 52 (19.2%) patients, including 7
      cases of in-frame deletion in exon 19 and 3 cases of amino acid substitution in
      exon 21. Mutation rate was significantly higher in adenocarcinoma, adeno-squamous
      carcinoma, and bronchioloalveolar cancer than in squamous cell carcinoma [26.1%
      (6/23), 40.0% (2/5), and 50.0% (2/4) vs. 0 (0/20), P=0.025], and significantly
      higher in non-smokers than in smokers [41.8% (7/17) vs. 8.6% (3/35), P=0.009].
      Mutation rate in women was similar to that in men [23.1% (3/13) vs. 18.0% (7/39),
      P=0.697]. CONCLUSION: EGFR mutation rate in Chinese NSCLC patients is similar to
      that in Japanese patients, and is obviously higher than that in Caucasian
      population.

PMID- 16086867
TI  - [Correlation of HERG K+ channel protein expression to chemosensitivity of tumor
      cells to doxorubicin and its modulation by erythromycin].
AB  - BACKGROUND & OBJECTIVE: Previous studies have found that HERG, a kind of K(+)
      channel protein, is expressed in some cancers, but its expression is weak or lost
      in normal tissues. This study was to investigate HERG expression in various
      cancer cell lines, its correlation with chemosensitivity of cancer cells to
      doxorubicin, and its biochemical modulation. METHODS: HERG expression in human
      colon carcinoma cell line HT-29, human breast carcinoma cell line MCF-7, human
      lung carcinoma cell line A549, and human high-metastatic giant cell lung
      carcinoma cell line PG was analyzed by Western blot. After transfection of herg
      gene, the cytotoxicity of doxorubicin, erythromycin (a HERG K+ channel blocker),
      or doxorubicin in combination with erythromycin to cancer cells was analyzed by
      MTT assay. Intracellular content of doxorubicin was observed under fluorescent
      microscope. RESULTS: HERG protein level was higher in HT-29, MCF-7, and PG cells
      than in A549 cells. A549 cells were more sensitive to doxorubicin than HT-29
      cells. The 50% inhibitory concentration (IC(50)) of doxorubicin was obviously
      higher in herg-transfected A549 cells than in parent A549 cells. Erythromycin
      obviously suppressed the growth of HT-29 cells, and showed synergic cytotoxicity
      with doxorubicin to HT-29 cells. There is no difference in intracellular
      doxorubicin content among herg-transfected A549 cells, pCDNA3.1-transfected A549
      cells, and parent A549 cells. CONCLUSIONS: HERG expression might negatively
      correlate with the chemosensitivity of tumor cells to doxorubicin. Erythromycin
      may act as a modulator, and has synergic effect with doxorubicin. HERG may serve
      as a molecular marker and modulating target for individualized cancer therapy.

PMID- 16086868
TI  - [Inhibitory effect of sodium butyrate on 1,2-dimethylhydrazine-induced
      tumorigenesis of colorectal cancer in mice].
AB  - BACKGROUND & OBJECTIVE: In vitro studies proved that sodium butyrate (NaB) could
      stimulate cell differentiation, inhibit cell proliferation, and induce cell
      apoptosis in various tumors. This study was to evaluate the preventive effects of
      coloclysis of NaB on 1,2-dimethylhydrazine (DMH)-induced tumorigenesis of
      colorectal cancer in mice. METHODS: The mice of Kunming species were divided into
      5 groups and received relevant treatments: DMH alone group (with subcutaneous
      injection of 30 mg/kg of DMH weekly for 11 weeks), control (normal saline, NS)
      group, DMH plus low dose of NaB (1.25 mol/kg, 24-week coloclysis) group, DMH plus
      high dose of NaB (2.5 mol/kg, 24-week coloclysis) group, and high dose of NaB
      group. The mice were killed in batches at the 12th, 18th, and 24th weeks of
      carcinoma induction separately. The incidence of colorectal tumor in each group
      was observed. Meanwhile, the general condition, body weight increasing, liver and
      renal functions, and pathologic changes of liver, kidney, lungs, and pancreas of
      the mice in DMH plus high dose of NaB group were also observed. RESULTS: No tumor
      was observed at the 12th week in each group. At the 18th week, the tumor
      incidence was significantly higher in DMH alone group and DMH plus low dose of
      NaB group than in DMH plus high dose of NaB group (58.3%, and 25.0% vs. 0, P <
      0.01). At the 24th week, the tumor incidence was 95.0% in DMH alone group, 45.0%
      in DMH plus low dose of NaB group, and 15.0% in DMH plus high dose of NaB group;
      the differences among the 3 groups were significant (P=0.01, P < 0.01). No tumor
      was observed in control group and high dose of NaB group. There was no difference
      in the general condition, body weight increasing, and liver and renal functions
      of the mice between control group and high dose of NaB group (P > 0.05); no
      pathologic changes in liver, kidney, lungs, and pancreas were observed in the
      mice in high dose of NaB group. CONCLUSION: NaB could inhibit DMH-induced
      tumorigenesis of colorectal cancer in mice with no obvious toxicity.

PMID- 16086869
TI  - [Antitumor and anti-angiogenic effects of manumycin on human hepatocellular
      carcinoma HepG2 xenografts in nude mice].
AB  - BACKGROUND & OBJECTIVE: Farnesyl-transferase inhibitor manumycin has in vitro and
      in vivo antitumor effects on pancreatic cancer, colon cancer, and anaplastic
      thyroid carcinoma. Our previous experiments showed that manumycin could inhibit
      proliferation pathway and survival pathway in human hepatocellular carcinoma
      HepG2 cells in vitro. This study was to examine the antitumor and anti-angiogenic
      effects of manumycin on HepG2 xenografts in nude mice. METHODS: The xenografts
      derived from HepG2 cells were established in BALB/C nude mice. Inoculated mice
      were randomly divided into normal saline (NS) group, positive control
      (cyclophosphamide, CTX, 25 mg/kg) group, negative control (0.1% Me2SO, 20 ml/kg)
      group, low dose munumycin (2.5 mg/kg) group, and high dose munumycin (5 mg/kg)
      group. Tumor volume was measured in nude mice bearing xenografts. Microvessel
      density (MVD) was observed by immunohistochemistry. Protein levels of vascular
      endothelial growth factor (VEGF) and b-fibroblast growth factor (b-FGF) were
      determined by Western blot; mRNA level of VEGF was analyzed using reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: The mean tumor volume
      ratio of nude mice xenograft (V/V(0)) was significantly lower in low dose
      manumycin group and high dose manumycin group than in negative control group
      (0.68+/-0.09 and 0.59+/-0.04 vs. 1.38+/-0.21, P < 0.01). MVD was significantly
      lower in manumycin-treated groups than in control group (P < 0.01). Manumycin
      significantly down-regulated protein level of VEGF in HepG2 cells and HepG2
      xenografts, and mRNA level of VEGF in HepG2 xenografts, but didn't affect protein
      level of b-FGF. CONCLUSIONS: Manumycin could inhibit the growth of human
      hepatocellular carcinoma HepG2 xenografts in nude mice. The down-regulation of
      VEGF expression and the inhibition of angiogenesis might play a key role in the
      anti-neoplastic effect of manumycin.

PMID- 16086870
TI  - [Antitumor effect of diallyl disulfide on human gastric cancer MGC803 cells
      xenograft in nude mice].
AB  - BACKGROUND & OBJECTIVE: Diallyl disulfide (DADS) can inhibit growth of various
      cancer cell lines in vitro, but little is known about its in vivo antitumor
      effect. This study was designed to investigate effect of DADS on growth of human
      gastric carcinoma MGC803 cells xenograft in BALB/C nude mice. METHODS: MGC803
      cells, with or without 1-day treatment of DADS (30 mg/L), were subcutaneously
      transplanted into the right axial regions of nude mice. The xenograft tumor
      growth in mice was observed after in vitro treatment or intraperitoneal injection
      of DADS. Proliferating cell nuclear antigen (PCNA) expression was detected by
      Western blot. RESULTS: No xenograft tumor was observed in the nude mice
      inoculated with DADS-treated MGC803 cells. When injected with 50, 100, and 200
      mg/kg of DADS, the inhibition rate of tumor growth in the nude mice inoculated
      with untreated MGC803 cells were 27.8%, 66.1%, and 73.0%; the expression of PCNA
      was inhibited. CONCLUSION: DADS could suppress incidence of human gastric
      carcinoma xenograft in BALB/C nude mice, and inhibit growth of transplanted
      tumor.

PMID- 16086871
TI  - [Effect of RNAi-mediated survivin gene silencing on apoptosis of ovarian cancer
      cell lines SKOV3 and SKOV3/ADM].
AB  - BACKGROUND & OBJECTIVE: RNA interference (RNAi) has been widely used in tumor
      gene therapy, antivirus, and gene drug selection. Survivin gene is highly
      expressed in ovarian cancer cell line SKOV3 and drug-resistant cell line
      SKOV3/ADM, and is an ideal target of gene therapy for ovarian cancer. This study
      was to explore effect of RNAi-mediated Survivin gene silencing on apoptosis of
      SKOV3 and SKOV3/ADM cells. METHODS: Recombinant plasmid pshRNA-Survivin was
      transfected into SKOV3 and SKOV3/ADM cells. The expression of Survivin was
      detected by semi-quantitative reverse transcription-polymerase chain reaction (RT
      PCR) and Western blot. The apoptosis of SKOV3 and SKOV3/ADM cells after
      transfection were evaluated by AO/EB dyeing, TUNEL, and flow cytometry. RESULTS:
      After transfection of pshRNA-Survivin, mRNA and protein levels of Survivin gene
      in SKOV3 and SKOV3/ADM cells were obviously reduced; the apoptosis of SKOV3 and
      SKOV3/ADM cells were significantly higher in transfection group than in control
      group (P0.01); 48 h after transfection, the apoptosis rate was 14.05% in SKOV3
      cells, and 21.02% in SKOV3/ADM cells, no obvious apoptosis was detected in
      control cells. CONCLUSION: pshRNA-Survivin could reduce the expression of
      Survivin gene, and induce apoptosis of SKOV3 and SKOV3/ADM cells.

PMID- 16086872
TI  - [Effect of inhibiting survivin expression with antisense oligodeoxynucleotides on
      sensitivity of hepatocellular carcinoma cell lines HepG2 and HepG2/ADM to
      adriamycin].
AB  - BACKGROUND & OBJECTIVE: Survivin deserves attention as a selective target for
      cancer therapy because it is silenced in differentiated adult tissues, but is
      expressed in a variety of human tumors, and is involved in tumorigenesis and
      chemoresistance. Antisense oligodeoxynucleotides (ASODN) can be used to inhibit
      the expression of survivin to induce apoptosis or enhance chemosensitivity of
      tumor cells. This study was to investigate the effect of inhibiting survivin
      expression with ASODN on sensitivity of hepatocellular carcinoma cell lines HepG2
      and HepG2/ADM to Adriamycin (ADM). METHODS: The expression of survivin in HepG2
      and HepG2/ADM cells was detected by reverse transcription-polymerase chain
      reaction (RT-PCR) and Western blot. Sensitivities of HepG2 and HepG2/ADM cells to
      ASODN and ADM were detected by MTT assay. ASODN was transfected into HepG2 and
      HepG2/ADM cells; expression of survivin was detected by RT-PCR. Synergetic
      effects of low concentrations of ASODN and subtoxic concentrations of ADM on
      HepG2 and HepG2/ADM cells were detected by isobolography. The expression of
      active Caspase-3 and cell apoptosis were evaluated by flow cytometry. RESULTS:
      mRNA level of survivin in HepG2/ADM cells was 15 folds as that in HepG2 cells;
      protein level of Survivin in HepG2/ADM cells was 18 folds as that in HepG2 cells.
      Both HepG2 and HepG2/ADM cells were sensitive to ASODN-mediated cytotoxicity in a
      concentration-dependent manner. The 50% inhibitory concentration (IC(50)) of
      ASODN was 317.90 nmol/L for HepG2 cells, and 480.74 nmol/L for HepG2/ADM cells.
      The maximal cytotoxicity was observed at 500 nmol/L of ASODN; the inhibitory rate
      was 71.10% in HepG2 cells, and 53.67% in HepG2/ADM cells. The IC(50) of ADM was
      0.36 microg/ml for HepG2 cells, and 2.12 microg/ml for HepG2/ADM cells; the
      resistance index was 6. ASODN efficiently down-regulated mRNA level of survivin
      in both cell lines in a concentration-dependent manner. For HepG2 cells, with the
      IC(50) of 271.93 nmol/L, the maximal effect of ASODN was achieved at a
      concentration of 400 nmol/L, at which mRNA level of survivin was down-regulated
      by 69.12%; for HepG2/ADM cells, with the IC(50) of 365.72 nmol/L, its maximal
      effect was achieved at a concentration of 400 nmol/L, at which mRNA level of
      survivin was down-regulated by 60.01%. ASODN in combination with ADM
      synergetically enhanced sensitivity of HepG2 cells to ADM by 6 folds, and
      HepG2/ADM cells by 4 folds. Combination treatment of ASODN and ADM gradually
      enhanced activity of Caspase-3 and cell apoptosis in a concentration-dependent
      manner, and resulted in caspase-dependent cell death in HepG2/ADM cells.
      CONCLUSION: Inhibiting survivin expression with ASODN could sensitize
      hepatocellular carcinoma cells to ADM, and the combination of ASODN and ADM may
      be a reasonable approach for clinical treatment of ADM-resistant hepatocellular
      carcinoma.

PMID- 16086873
TI  - [Synergetic cytotoxicity of cisplatin and etoposide to leukemia cell line K562
      and its mechanism].
AB  - BACKGROUND & OBJECTIVE: Etoposide (VP-16) is one of the most common chemotherapy
      drugs, but its usage is limited by drug resistance. Some researches on solid
      tumors show that cisplatin (DDP) have synergetic effect with VP-16. This study
      was to evaluate synergetic cytotoxicity of VP-16 and DDP to leukemia cell line
      K562, and explore the mechanism. METHODS: K562 cells were treated with VP-16 (0
      or 5 microg/ml) and DDP (0, 0.3, 3, 15, or 30 microg/ml) in different combination
      patterns. Inhibitory effect of VP-16 and DDP on survival of K562 cells was
      measured by MTT assay. Cell apoptosis was evaluated by AO/EB double fluorescent
      labeling. The expression of topoisomerase (TOPO) II alpha and II beta, and
      transcription factor Sp1 and Sp3 were measured by semi-quantitive reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: MTT
      assay showed significant synergetic cytotoxicity of VP-16 and DDP. VP-16 in
      combination with DDP obviously enhanced cell apoptosis. RT-PCR showed that DDP
      significantly up-regulated the expression of TOPO II and Sp1 in concentration
      dependent manners (TOPO II alpha, II beta, and Sp1 were up-regulated by 36%, 25%,
      and 75% of control, respectively, when treated with 30 microg/ml of DDP), and
      down-regulated Sp3 by 49% of control; VP-16 (5 microg/ml) down-regulated TOPO II
      alpha by 71.9%, and up-regulated Sp3 by 14%; VP-16 (5 microg/ml) in combination
      with DDP (30 microg/ml) up-regulated TOPO II alpha by 83%, II beta by 11%, and
      Sp1 by 58% when compared with using VP-16 alone (but the levels were lower than
      using DDP alone), and down-regulated Sp3 by 61.3% when compared with using DDP
      alone. Western blot showed similar results to RT-PCR. CONCLUSION: Through up
      regulating TOPO II, DDP could enhance the chemotherapeutic effect of VP-16 on
      K562 cells by provide more target enzyme to act on.

PMID- 16086874
TI  - [Effect of HBV X gene transfection on octreotide-inhibited growth of
      hepatocellular carcinoma cell line HepG2].
AB  - BACKGROUND & OBJECTIVE: In vitro and in vivo experiments have shown that
      octreotide, a kind of somatostatin analogue, could inhibit hepatocellular
      carcinoma (HCC) growth. However, its clinical efficacy is unsatisfactoryu the
      reason is unclear. This study was to investigate if some characters of HCC cells
      transfected with hepatitis B virus (HBV) x gene have altered their response to
      octreotide, and explore the possible mechanisms. METHODS: The proliferation of
      HCC cell lines HepG2 and HepG2x (with HBV x gene transfection) was measured by
      (3)H-thymidine incorporation into DNA. Immunocytochemistry was used to detect the
      expression of proliferating cell nuclear antigen (PCNA) in tumor cells. Annexin-V
      and TUNEL in situ assays were used to detect apoptotic cells. The expressions of
      extracellular signal-regulated kinase (ERK-1/ERK-2) and somatostatin receptors
      (SSTR-2, SSTR-3, SSTR-5) were measured with Western blot. RESULTS: At the
      concentration of 1 x 10(-5) - 1 x 10(-9) mol/L, octreotide significantly
      inhibited (3)H-TdR incorporation into HepG2 cells in a dose-dependent manner (r=
      0.917, P < 0.01) and PCNA expression, and greatly enhanced the apoptosis of HepG2
      cells either in Annexin V positive rate [control vs. octrotide=(1.18+/-0.13)% vs.
      (14.20+/-2.57)%, P < 0.05] or TUNEL apoptotic index [control vs. octrotide=(3.6+/
      0.9)% vs. (18.8+/-3.3)%, P < 0.05]. However, no such response happened in HepG2x
      cells when treated with octrotide or octrotide plus lamivudine. The expressions
      of SSTR-2 and SSTR-5 were significantly lower in HepG2x cells than in HepG2 cells
      (P < 0.01); the expressions of ERK-1 and ERK-2 were significantly higher in
      HepG2x cells than in HepG2 cells (P < 0.05). Octreotide didn't inhibit ERKs
      expression in HepG2x cells. CONCLUSION: The down-regulated expression of SSTR-2
      and SSTR-5, due to HBV x gene transfection, result in decreased growth inhibitory
      effects of octreotide on HepG2x cells.

PMID- 16086875
TI  - [Antitumor effects of ring-closed and ring-opened hydroxycamptothecin on oral
      squamous carcinoma cell line Tca8113].
AB  - BACKGROUND & OBJECTIVE: The antitumor effect of hydroxycamptothecin (HCPT)
      closely relates with its lactone form (including ring-closed form and ring-opened
      form), but the antitumor effects of ring-closed HCPT (C-HCPT) and ring-opened
      HCPT (O-HCPT) remain controversial. Researches have showed that O-HCPT has
      obvious in vitro and in vivo antitumor effects on oral squamous cell carcinoma.
      This study was to compare the antitumor effects of C-HCPT and O-HCPT on oral
      squamous carcinoma cell line Tca8113, and explore the mechanisms. METHODS:
      Tca8113 cells and its xenografts in BALB/C nude mice were treated with C-HCPT and
      O-HCPT. The cytotoxicity of HCPT was measured by MTT assay. Cell cycle was
      detected by flow cytometry. The growth state of Tca8113 cells xenografts was
      observedu the tumor doubling time and inhibition rate were calculated. The
      concentration of total HCPT in plasma and tumor tissue was quantitated by high
      performance liquid chromatography (HPLC); the pharmacokinetic parameters were
      estimated. RESULTS: C-HCPT and O-HCPT showed similar cytotoxicity effects on
      Tca8113 cells in vitro. Low concentration of HCPT (< 1 micromol/L) arrested cell
      cycle of Tca8113 cells at S phase and G(2)/M phase; high concentration of HCPT
      (100 micromol/L) obviously induced apoptosis of Tca8113 cells. Compared with
      control group, the xenografts of HCPT-treated group grew slowly, and the tumor
      doubling time was prolonged. The tumor inhibition rates were 69.6% (3 mg/kg of O
      HCPT), 65.0% (3 mg/kg of C-HCPT), and 74.1% (10 mg/kg of O-HCPT), respectively.
      The plasma AUC was 2.66 microg . h . ml(-1) for C-HCPT (10 mg/kg) and 0.42 microg
      . h . ml(-1) for O-HCPT (10 mg/kg). HCPT could be detected in tumor tissue. No
      obvious toxicity was observed in 3 mg/kg of HCPT group; obvious gastrointestinal
      reaction was observed in 10 mg/kg of O-HCPT group; all nude mice in 10 mg/kg of C
      HCPT group died 2 days after treatment. CONCLUSIONS: Both C-HCPT and O-HCPT have
      strong in vitro and in vivo cytotoxic effects on Tca8113 cells, which relate to
      cell cycle arrest and cell apoptosis inducement. Cytotoxicity of C-HCPT is more
      severe than that of O-HCPT.

PMID- 16086876
TI  - [Reverse effect of genetically modified adenovirus H101 on drug-resistance of
      A549/DDP cells to cisplatin].
AB  - BACKGROUND & OBJECTIVE: Multidrug resistance is one of the main causes of
      treatment failure of chemotherapy. Reversal agents may be used to reverse drug
      resistance. To date, no appropriate reversal agent is used clinically. This study
      was to evaluate reverse effect of genetically modified adenovirus H101 on drug
      resistance of A549/DDP cells to cisplatin (DDP), and to explore its mechanisms.
      METHODS: Lung adenocarcinoma cell line A549 and its DDP-resistant cell line
      A549/DDP were treated with DDP and H101. Reverse effect of H101 on drug
      resistance of A549/DDP to DDP was tested by MTT assay. The levels of cellular
      multidrug resistant protein 1 (MRP1), glutathione-S-transferase (GST), and
      topoisomerase-II (TOPO-II) were detected by flow cytometry (FCM). The level of
      intracellular glutathione (GSH) was measured by fluorescence-Coomassie light blue
      method. The intracellular concentration of platinum was measured by atomic
      absorption spectrometry. RESULTS: The resistance index of A549/DDP cells to DDP
      was 14.3. After infection of H101, the 50% inhibitory concentration (IC(50)) of
      DDP to A549/DDP cells reduced from 352.4 micromol/L to 61.6 micromol/L by 5.7
      folds. Protein levels of GST and TOPO-II were higher in A549/DDP cells than in
      A549 cells, which were markedly decreased in A549/DDP cells after infection of
      H101. No MRP1 protein was detected in both A549 cells and A549/DDP cells.
      Intracellular amount of GSH in A549/DDP cells was 2 times higher than that in
      A549 cells, which was significantly decreased after infection of H101. The
      concentration of platinum in A549 cells was 3 times higher than that in A549/DDP
      cells. After infection of H101, the concentration of platinum in A549 cells had
      no significant change, but that in A549/DDP cells was significantly increased.
      CONCLUSION: H101 may reverse drug-resistance of A549/DDP cells to DDP through
      down-regulating GST and TOPO-IIand increasing intracellular cumulation of
      platinum.

PMID- 16086877
TI  - [Efficacy of gefitinib on Chinese patients with locally advanced or metastatic
      non-small cell lung cancer: a clinical trial].
AB  - BACKGROUND & OBJECTIVE: Gefitinib, a selective inhibitor of epidermal growth
      factor receptor (EGFR) tyrosine kinase, has been approved to be used in treatment
      of locally advanced or metastatic non-small cell lung cancer (NSCLC) in many
      countries. This study, a multicenter clinical trial, was designed to evaluate the
      efficacy of gefitinib on Chinese patients with locally advanced or metastatic
      NSCLC after failure of previous chemotherapy, and explore its safety. METHODS: A
      total of 159 pathologically-confirmed NSCLC patients were enrolled. Gefitinib was
      orally administered 250 mg once daily until disease progression or the occurrence
      of intolerable toxicity. RESULTS: The objective response rate was 27.0%; the
      disease control rate was 54.1%. The median progression-free survival time was 97
      days; the median overall survival time was 10.0 months; the 1-year survival rate
      was 44%. The most common drug-related adverse events were rash (44.0%), pruritus
      (15.7%), and diarrhea (10.1%), and most of them were grade 1-2 events with no
      need of further treatment. CONCLUSION: Gefitinib is effective and safe in
      treating Chinese patients with locally advanced or metastatic NSCLC after failure
      of previous chemotherapy.

PMID- 16086878
TI  - [A randomized trial of docetaxol plus cisplatin versus gemzar plus cisplatin in
      treating advanced non-small cell lung cancer].
AB  - BACKGROUND & OBJECTIVE: Treating advanced non-small cell lung cancer (NSCLC) is
      difficult. The response rate (RR) of NSCLC patients to traditional chemotherapy
      regimen is about 40%. Now the RR has been improved with application of new drugs,
      such as taxol, docetaxal, and gemzar. This randomized trial was designed to
      determine treatment efficacies of docetaxol plus cisplatin and gemzar plus
      cisplatin on advanced NSCLC, and observe their cytotoxicities. METHODS: A total
      of 43 advanced NSCLC patients were randomized into 2 groups, 22 in TP group
      (docetaxol plus cisplatin) and 21 in GP group (gemzar plus cisplatin), and
      received relevant treatments. The RR, time to progression (TTP), mean survival
      time (MST), and 1- and 2-year survival rates of the patients were analyzed.
      RESULTS: The RR was 45.4% in TP group with 1 case of complete remission (CR) and
      9 cases of partial remission (PR), and 42.9% in GP group with 9 cases of PR. The
      TTP was 4.6 months in TP group, and 4.7 months in GP group; the MST was 10.6
      months in TP group [95% confidence interval (CI), 9.3-11.3 months], and 11.3
      months in GP group (95% CI, 6.8-14.8 months). The 1- and 2-year survival rates
      were 38.1% and 15.3% in TP group, and 34.1% and 11.2% in GP group. The
      differences of RR and survival rate between the 2 groups were not significant
      (P=0.71, P=0.89). The major cytotoxicity of TP was leukopeniau the major
      cytotoxicities of GP group were fatigue and thrombocytopenia. All adverse
      reactions were tolerable. CONCLUSION: TP and GP regimens may enhance the
      remission rate of NSCLC patients with tolerable adverse reaction, and improve the
      short-term survival rate, but the differences in treatment efficacies of TP and
      GP groups are not significant.

PMID- 16086879
TI  - [Efficacy of NO regimen and NP regimen on advanced non-small cell lung cancer: a
      prospective randomized trial].
AB  - BACKGROUND & OBJECTIVE: Oxaliplatin (LOHP) is an effective drug in treatment of
      non-small cell lung cancer (NSCLC) with mild toxicities to gastrointestinal
      tract, kidney, and bone marrow. Cisplatin (DDP) plus vinorelbine (NVB) constitute
      the first-line regimen (NP regimen) for NSCLC. This study was to compare the
      short-term response, long-term outcome, and adverse events between advanced NSCLC
      patients received NO regimen (LOHP plus NVB) and NP regimen. METHODS: A total of
      90 patients with advanced NSCLC were randomized into NO group (58 patients, 25
      mg/m(2) of NVB, day 1 and day 8; 130 mg/m(2) of LOHP, day 1) and NP group (32
      patients, 25 mg/m(2) of NVB, day 1 and day 8; 50 mg/m(2) of DDP, day 2 and day
      3). The short-term response, long-term outcome, adverse events, and survival
      status of the 2 groups were observed. RESULTS: The response rates were 33.33% in
      NO group, and 35.48% in NP group, but no significant difference was detected
      between the 2 groups (P > 0.05). The clinical benefit response rate was
      significantly higher in NO group than in NP group (80.70% vs. 64.52%, P < 0.05).
      The median time to progression (TTP) was 17 weeks in NO group, and 15 weeks in NP
      group; the median time of remission was 21 weeks in NO group, and 19 weeks in NP
      group; the median survival time was 39 weeks in NO group, and 37 weeks in NP
      group; the 1-year survival rate was 37.93% in NO group, and 31.25% in NP group.
      No significant differences were detected between the 2 groups. The incidence
      rates of phlebitis and grade I-II peripheral neuritis were significantly higher
      in NO group than in NP group (77.59% vs. 50.00%, P<0.01; 43.10% vs. 15.63%,
      P<0.01). The incidence rate of grade III-IV nausea/vomiting was significantly
      higher in NP group than in NO group (31.25% vs. 3.45%, P<0.05). CONCLUSIONS: The
      efficacy of NO regimen on advanced NSCLC is similar to that of NP regimen, but
      the clinical benefit response rate is higher in NO group than in NP group. In
      short, NO regimen may be recommended as the first-line chemotherapy regimen for
      advanced NSCLC.

PMID- 16086880
TI  - [Selecting postoperative chemotherapy regimen and optimizing therapy cycle for
      stage II-IV ovarian epithelial carcinoma].
AB  - BACKGROUND & OBJECTIVE: The postoperative chemotherapy for ovarian epithelial
      carcinoma need to be improved. This study was conducted to seek suitable
      chemotherapy for patients with stage II-IV ovarian epithelial carcinoma. METHODS:
      The records of 325 patients with stage II-IV ovarian epithelial carcinoma,
      received different postoperative chemotherapy (HCBP, CP, CBP, or CAP) regimens
      for different cycles from Jan. 1986 to Dec. 2000 in our cancer center, were
      analyzed retrospectively. The treatment outcome and prognosis of these patients
      were analyzed. RESULTS: The 5-year survival rate of the patients received HCBP
      regimen was significantly higher than those of the patients received CP, CBP, or
      CAP regimens (84.3% vs. 43.0%, P=0.008; 46.1%, P=0.016; and 40.0%, P=0.002). The
      incidence of chemotherapy-related complications was significantly lower in the
      patients received CP regimen than in the patients received HCBP, CBP, or CAP
      regimens (76.0% vs. 91.3%, P=0.015; 88.2%, P=0.043; and 87.7%, P=0.038). The 5
      year survival rates of the patients received more than 6 or 5-6 cycles were
      significantly higher than that of the patients received less than 5 cycles (56.2%
      or 59.5% vs. 35.1%, P< 0.001). The incidences of chemotherapy-related
      complications in such patients were 89.6%, 81.1%, and 82.8% (P=0.214),
      respectively. CONCLUSIONS: We recommend 5-6 cycles of CP-based chemotherapy
      regimens for stage II-IV ovarian epithelial carcinoma. Prolonging the duration of
      each chemotherapy cycle might achieve good prognosis.

PMID- 16086881
TI  - [Preventive efficacies of china-made tropisetron hydrochloride and Navoban on
      chemotherapy-induced nausea and vomiting: a randomized controlled clinical
      trial].
AB  - BACKGROUND & OBJECTIVE: Navoban (import tropisetron hydrochloride) can
      effectively prevent chemotherapy-induced nausea and vomiting; however, it is too
      expensive to be used extensively in clinic. This study was designed to compare
      the antiemetic efficacies and side effects of China-made tropisetron
      hydrochloride with Navoban. METHODS: A multicenter and randomized controlled
      trial was carried out. A total of 132 cancer patients were randomized into 2
      groups and received 5 mg of China-made tropisetron hydrochloride (group A, 66
      patients) or Navoban (group B, 66 patients) intravenously before cisplatin- or
      adriamycin-based chemotherapy. The gastrointestinal reactions induced by
      chemotherapy and side effects of the antiemetics were recorded within 7 days
      after chemotherapy. RESULTS: Acute nausea was prevented completely in 48.5% of
      the patients in group A and in 43.8% of group B; acute vomiting was prevented
      completely in 69.7% of the patients in group A and in 67.2% of group B. Delayed
      nausea was prevented completely in 25.8% of the patients in group A and in 28.1%
      of group B; delayed vomiting was prevented completely in 47.0% of the patients in
      group A and in 51.6% of group B. No significant differences in complete control
      of nausea and vomiting showed between group A and group B (P > 0.05). Both
      antiemetic regimens were well tolerated, and no difference in adverse events
      between the 2 groups was observed (P > 0.05). CONCLUSION: China-made tropisetron
      hydrochloride is as effective as Navoban in the prevention of chemotherapy
      induced nausea and vomiting, and only causes mild, infrequent side effects.

PMID- 16086882
TI  - [Impact of dose delivery of postoperative first-line chemotherapy on prognosis of
      stage III C epithelial ovarian carcinoma].
AB  - BACKGROUND & OBJECTIVE: Chemotherapy, which includes selecting appropriate drugs
      and suitable dose, is necessary to advanced ovarian carcinoma. Whether dose
      delivery affects prognosis of ovarian cancer is controversial. This study was to
      investigate the impact of dose delivery of postoperative first-line chemotherapy
      on prognosis of stage III C epithelial ovarian carcinoma. METHODS: Clinical data
      of 47 stage III C epithelial ovarian carcinoma patients, treated with cisplatin
      based adjuvant first-line chemotherapy, were retrospectively analyzed. The
      relative cumulative dose (CD) and dose intensity (DI) were calculated for each
      drug and for all drugs combined (namely overall CD and overall DI). The impact of
      dose delivery on progression-free survival (PFS) and overall survival (OS) was
      analyzed. RESULTS: Median overall CD was 0.76, and median overall DI was 0.53;
      the median CD of cisplatin was 0.78, and the median DI of cisplatin was 0.57; the
      median CD of paclitaxel was 0.81, and the median DI of paclitaxel was 0.51. Dose
      delivery had no impact on PFS and OS of the patients. However, in non-paclitaxel
      chemotherapy subgroup, the higher overall CD, or CD for cisplatin, or DI for
      cisplatin, the longer PFS (P=0.01, P=0.03, P=0.01) and OS (P=0.01, P=0.04,
      P=0.01); in paclitaxel chemotherapy subgroup, dose delivery had no impact on PFS
      and OS. In suboptimal surgery subgroup (residual disease of > 2 cm), the higher
      DI for cisplatin, the longer PFS; the higher overall CD, or DI for cisplatin, the
      longer OS. In optimal surgery subgroup (residual disease of < or =2 cm), dose
      delivery had no impact on PFS and OS. Residual disease was the only independent
      prognostic factor of epithelial ovarian carcinoma. CONCLUSIONS: The dose delivery
      below standard level may influence survival of the patients with residual disease
      of > 2 cm or treated by non-paclitaxel chemotherapy. The diameter of residual
      disease is the independent prognostic factor of epithelial ovarian carcinoma.

PMID- 16086883
TI  - [Expression of glycoprotein 90K in non-Hodgkin's lymphoma and its clinical
      significance].
AB  - BACKGROUND & OBJECTIVE: 90K, a kind of secretory glycoprotein, is related to
      prognosis of some tumors. So far, little is reported on its relation to prognosis
      of non-Hodgkin's lymphoma (NHL). This study was to explore the 90K expression in
      naive NHL tissues and its clinical significance. METHODS: 90K expression in 110
      specimens of NHL was detected by immunohistochemistryu its correlations to short
      term treatment efficacy of CHOP regimen and long-term survival of the patients
      were analyzed retrospectively. RESULTS: Of the 110 NHL specimens, 36 (32.7%)
      showed negative expression of 90K, 27 (24.5%) showed weak expression, 17 (15.5%)
      showed fairly strong expression, and 30 (27.3%) showed strong expression; the
      positive rate of 90K in NHL tissue was 67.3%. 90K expression had no correlation
      to gender, age, IPI and other clinicopathologic characteristics. All patients
      received treatment of standard CHOP regimen; the response (complete remission and
      partial remission) rate was significantly higher in low 90K expression (negative
      and weak expression) group than in high 90K expression (fairly strong and strong
      expression) group [82.5% (52/63) vs. 65.2% (30/46), P=0.039], but 90K expression
      had no correlation to long-term survival (P > 0.05). CONCLUSIONS: 90K expression
      may be applied to predict short-term efficacy of CHOP regimen on NHL. However,
      whether 90K could become a prognostic tumor marker of NHL needs further research.

PMID- 16086884
TI  - [Expression of MUC1 gene and MDR1 gene in non-M3 subtype acute leukemia and their
      correlations to clinical treatment efficacy].
AB  - BACKGROUND & OBJECTIVE: Mucin 1 (MUC1) gene is expressed in various tumors, and
      overexpressed in acute leukemia. This study was to evaluate the expression of
      MUC1 gene and multidrug-resistance protein-1 (MDR1) gene in non-M3 subtype acute
      leukemia and their correlations to clinical treatment efficacy. METHODS: The
      expression of MUC1 and MDR1 genes were measured in 34 patients with non-M3
      subtype acute leukemia by reverse transcription-polymerase chain reaction (RT
      PCR); their correlations to clinical treatment efficacy were observed. RESULTS:
      The positive rate of MUC1 gene in the 34 patients was 50.0%, and the positive
      rate of MDR1 gene was 29.4%. The positive rate of MDR1 was significantly higher
      in MUC1-positive patients than in MUC1-negative patients (52.9% vs. 5.9%,
      P=0.003). Complete remission (CR) rate was significantly higher in MUC1-negative
      patients than in MUC1-positive patients (94.1% vs. 52.9%, P<0.01). CR rate was
      significantly higher in MDR1-negative patients than in MDR1-positive patients
      (91.7% vs. 50.0%, P<0.05). In 9 patients with positive expression of both MUC1
      and MDR1, the CR rate was 55.6%; while in 16 patients with negative expression of
      both MUC1 and MDR1, the CR rate was 100%. CONCLUSIONS: The non-M3 subtype acute
      leukemia patients with positive expression of MUC1 have high positive rate of
      MDR1. The patients with negative expression of both MUC1 and MDR1 have high CR.
      Co-detection of MUC1 gene and MDR1 gene can predict treatment efficacy on non-M3
      subtype acute leukemia.

PMID- 16086885
TI  - [Expression of lung resistance protein and multidrug resistance-associated
      protein in naive childhood acute leukemia and their clinical significance].
AB  - BACKGROUND & OBJECTIVE: Previous studies revealed that lung resistance protein
      (LRP) and multidrug resistance-associated protein (MRP) relate to drug resistance
      of childhood leukemia, which is not caused by only one mechanism. This study was
      to evaluate the expression of LRP and MRP genes in childhood leukemia and their
      correlation. METHODS: The expression of LRP and MRP in 38 children with acute
      leukemia and 6 healthy children were measured with reverse transcription
      polymerase chain reaction (RT-PCR); their clinical significance was analyzed
      according to complete remission (CR) rate of the patients after chemotherapy.
      RESULTS: CR rate of the 38 patients was 68.4%. LRP was expressed in 11 of the 38
      patients, and didn't express in healthy controls; CR rate was significantly lower
      in LRP-positive patients than in LRP-negative patients (27.3% vs. 85.2%, P <
      0.05). MRP was overexpressed in 21 of the 38 patients; CR rate was significantly
      lower in MRP-positive patients than in MRP-negative patients (47.6% vs. 94.1%, P
      < 0.05). The positive rate of LRP was significantly lower in acute lymphoblastic
      leukemia (ALL) than in acute nonlymphocytic leukemia (ANLL) [18.5% (5/27) vs.
      45.5% (6/11), P < 0.05]; however, the positive rate of MRP was 59.3% (16/27) in
      ALL, and 45.5% (5/11) in ANLL (P > 0.05). The positive rate of MRP was 28.6% in
      LRP-positive patients, and 29.4% in LRP-negative patients; there was no
      correlation between LRP and MRP. CONCLUSION: Childhood acute leukemia patients
      with overexpression of LRP and MRP suffer severe disease and achieve low
      remission rateu lower remission rate of childhood ANLL patients may relate to LRP
      expression.

PMID- 16086886
TI  - [Application of adenosine triphosphate tumor chemosensitive assay system to
      individual chemotherapy for hepatocellular carcinoma].
AB  - BACKGROUND & OBJECTIVE: Present chemotherapy for hepatocellular carcinoma (HCC)
      is not effective. To improve the effect of chemotherapy, in vitro chemo-drug
      sensitive testing system, adenosine triphosphate tumor chemosensitive assay (ATP
      TCA) system, was used to evaluate efficacies of chemotherapeutic drugs, and to
      guide clinical individual chemotherapy for HCC patients. METHODS: ATP-TCA system
      was applied to test efficacies of 5-fluorouracil (5-FU), mitomycin (MMC),
      cisplatin (DDP), oxaliplatin (OXA), epirubicin (EPI), gemcitabine (GEM),
      irinotecan (CPT-11), etoposide (VP-16), and paclitaxel (PTX) on 50 HCC samples.
      Twenty-three HCC patients received ATP-TCA-directed chemotherapy (ATP-TCA group)u
      20 HCC patients received surgery and routine treatments (control group). Clinical
      outcomes of these patients were observed for 162 weeks. RESULTS: The assessable
      rate of ATP-TCA result is 90.8%. In the 50 samples, the sensitive (moderate to
      high degree) rates were 46% to PTX, 44% to CPT-11, 36% to GEM, 14% to MMC, 12% to
      EPI, 8% to DDP, 6% to VP-16, 6% to OXA, and 4% to 5-FU, respectively. In clinical
      trial, at the research end-point, no significant differences were found in
      partial remission (PR), complete remission (CR), stable disease (SD), and
      mortality between ATP-TCA group and control group (P > 0.05), but progression
      disease (PD) rate was significantly higher in control group than in ATP-TCA group
      (60.00% vs.13.04%, P=0.003); significant differences were found in overall
      response rate (ORR) (60.86% vs. 30.00%, P =0.043), overall survival (OS) (78.91
      weeks vs. 27.21 weeks, P=0.006), and progress-free survival (PFS) (30.52 weeks
      vs. 4.78 weeks, P=0.005) between ATP-TCA group and control group. CONCLUSIONS:
      ATP-TCA system might be useful in evaluating the efficacy of chemotherapeutic
      drugs on HCC samples, and in planning individualized chemotherapy regimen for HCC
      patients. PTX, CPT-11 and GEM might be potential drugs for the treatment of HCC.
      ATP-TCA-guided chemotherapy might prolong survival time of HCC patients.

PMID- 16086887
TI  - [Preparation and release efficiency of polylactic acid nanoparticle].
AB  - BACKGROUND & OBJECTIVE: As a new drug delivery carrier, medical nanoparticle (NP)
      appears to be very promising and are widely studied. Compare with microparticle,
      nanoparticle possesses several advantages, such as ultramicroscopic size, could
      be ingested by the cells after crossing the tissue matrix, and can penetrate the
      arterial wall and cross the blood-brain barrier. This study was to prepare
      polylactic acid (PLA) nanoparticle, and observe its morphology, diameter,
      structure, surface elements, and ability of in vitro drug release. METHODS: The
      biodegradable PLA was used as the carrier, and 5-fluorouracil (5-FU) was used as
      the model drug. 5-FU-PLA nanoparticle (5-FU-PLA-NP) was prepared by matrix and
      ultrasound emulsification. Morphology of 5-FU-PLA-NP was observed under scanning
      electron microscope; its surface elements were detected by X ray photoelectron
      spectroscopyu its drug loading (DL), embedding ratio (ER), and ability of in
      vitro drug release were assessed by ultraviolet spectroscopy. RESULTS: The
      nanoparticle was uniformly spherical with average diameter of (191+/-17) nm, DL
      of 15.2%, and ER of 45.6%. The nanoparticle showed sustained release character in
      the experiment of in vitro drug release: the cumulative drug release rate in
      analog body fluid was 94.3% at the 10th day. CONCLUSION: PLA-NP may serve as a
      carrier of 5-FU, and can change the pharmacokinetics of 5-FU, slower down drug
      release; 5-FU-PLA-NP can be prepared as intravenous injection, and may prolong
      the in vivo circulation time of 5-FU, so as to play more efficient antitumor
      effects.

PMID- 16086888
TI  - [Advancement of biotherapy for malignant lymphoma].
AB  - In the past 30 years, the incidence of lymphoma was increasing. Although it is
      very sensitive to chemotherapy, and many new cytotoxic drugs and chemotherapy
      regimens have emerged, the 5-year survival rate of lymphome patients is only 40%
      50%. With the development of immunology, the importance of biotherapy evoked more
      and more attention, and have became an important composition in the treatment of
      lymphoma. The most widely used biotherapy methods are listed as follows:
      monoclonal antibody, radioimmunotherapy, adoptive immunotherapy, active
      immunotherapy, gene therapy targeting Bcl-2, and targeted chemotherapy. Using
      these biotherapy methods in combination with other treatment methods reasonably
      will help to improve the short-term and long-term results of lymphoma.

PMID- 16086889
TI  - [Correlation of bone marrow stromal cells to leukemia and its research
      advancement in gene therapy for leukemia].
AB  - Bone marrow stromal cells (BMSCs) have a pluripotent characteristic, and can be
      readily isolated and expanded in vitro. After in vivo transplantation, BMSCs can
      home to blood marrow, and survive for a long time by self-renewing. They can
      influence the biological characteristics of leukemia cells from several aspects,
      and participate in the outbreak process and pathologic process of leukemia. BMSCs
      with normal functions have direct antitumur effects on leukemic cells. They can
      regulate the immunity remarkably. Genetically engineered BMSCs can deliver target
      therapeutic proteins over sufficient time after in vivo transplantation. Thus,
      BMSCs are considered to be an ideal therapeutic cell vehicle and target cells in
      the gene therapy for leukemia. Interferons, a cytokines family, are capable of
      producing multiplex biological effects, and have remarkable curative effects on
      hair cell leukemia and chronic myelogenous leukemia. Here we reviewed the
      possibility and perspective of molecular target therapy for leukemia by
      interferons-modified BMSCs.

PMID- 16086890
TI  - Outbreak of travel-related pontiac fever among hotel guests illustrating the need
      for better diagnostic tests.
AB  - BACKGROUND: Pontiac fever (PF), a legionellosis with influenza-like symptoms and
      high attack rates, is rarely reported. Travel-related outbreaks can elude
      detection because infected persons are often widely removed geographically from
      the transmission source before illness onset. Thirty-one persons staying at an
      Illinois hotel during August 9 to 11, 2002, reported influenza-like symptoms to
      local health departments within 24 to 48 hours of checkout. We investigated to
      identify the cause and source of illness to guide control measures. METHODS:
      Hotel water samples were collected for culture. A telephone questionnaire
      detailing illness symptoms and exposures was administered to all who were guests
      at the hotel from August 9 to 15 (n = 380). A case was defined as onset of fever,
      headache, and myalgia in a guest in the 14 days following the hotel stay. Patient
      sera were tested by hemagglutination assay for antibodies to Legionella species.
      RESULTS: Among 204 questionnaire respondents from 15 states and Canada, 50 met
      the case definition. Among persons exposed to the swimming pool/whirlpool spa
      area, 63% (47 of 75) became ill versus 3% (3 of 110) of unexposed persons
      (relative risk 23.0, 95% CI 7.4-71.1). Illness risk increased with increasing
      time exposed to the pool/spa. Approximately 95 to 115 bathers per day, two to
      three times above the usual number, used the spa during August 9 to 11. Three
      Legionella species, L. dumoffii, L. maceachernii, and L. micdadei, were isolated
      from spa filter backwash cultures. Two of 15 ill persons with acute- and
      convalescent-phase sera had a greater than fourfold rise in antibody titer to L.
      micdadei. CONCLUSIONS: PF was associated with exposure to a hotel pool/spa area.
      Heavy bather usage likely contributed to a decreased effectiveness of the
      disinfectant in the whirlpool spa, possibly promoting bacterial aerosolization.
      Linking case information from many states is essential in identifying and
      eliminating the source of disease transmission in travel-related outbreaks of PF.
      Clinicians should be aware of PF in the differential diagnosis of patients with
      influenza-like symptoms following recent travel, particularly with exposure to a
      communal-use whirlpool spa.

PMID- 16086891
TI  - Evaluation of yellow fever vaccination centers in Canada.
AB  - BACKGROUND: Health Canada regulates the designation of yellow fever vaccination
      centers (YFVCs) in Canada to ensure a national standard in the safe, effective,
      and appropriate use of yellow fever vaccine for Canadian travelers. The process
      for the designation of YFVC has evolved over the years, particularly with the
      development and implementation of specific criteria for designation. Standardized
      site visits in 1999 to 2001 demonstrated that noncompliance with the criteria
      jeopardized the objectives of the federal program. METHODS: A pilot evaluation
      questionnaire was developed and tested in seven YFVCs. The results provided the
      data necessary to appropriately adapt the questionnaire for on-site evaluations.
      The final questionnaire captured graded data on professional training, reference
      sources, services provided, and physical facilities and supplies. A minimum of
      60% was needed to pass the evaluation. The YFVCs were given individual feedback
      on their results and the opportunity to comply with standards. RESULTS: During
      the period of 2000 to 2001, 183 YFVCs were in operation in Canada. A random
      sample of 69 YFVCs were visited and evaluated for compliance to the circulated
      criteria. Fifty-two (75%) of the YFVCs received satisfactory results (range 70%
      and higher), and specific remedial recommendations were made to 8 (12%) clinics
      with a borderline result (range 60-69%). Nine (13%) of the YFVCs failed (range 0
      59%) the evaluation, with consequences ranging from notification of the
      infractions in writing to decertification. CONCLUSIONS: Although a majority of
      YFVCs met the evaluation criteria, a significant percentage (25%) of
      unsatisfactory and borderline compliance with Health Canada's criteria for
      designation of YFVCs means that there is a need for greater clarity and
      communication of the criteria and inspections for designated centers. To ensure
      that previously designated YFVCs and centers seeking designation consistently
      fulfill all the requirements, Health Canada is developing new methodologies of
      evaluation. The authors anticipate that all new and existing YFVCs will fully
      comply with the objective and specific criteria for designation.

PMID- 16086892
TI  - Higher venous bicarbonate concentration associated with hypoxemia, not acute
      mountain sickness, after ascent to moderate altitude.
AB  - BACKGROUND: The pathophysiology underlying acute mountain sickness (AMS) and
      excessive hypoxemia at high altitudes is not fully understood. Previous work by
      our group has demonstrated a significant association between urinary measures of
      dehydration and bicarbonate retention in subjects developing excessive hypoxemia
      and AMS at high altitudes. To further characterize these findings, we returned to
      our original testing site to examine the hypothesis that subjects with lower
      levels of oxygen saturation and/or AMS would possess higher levels of venous
      bicarbonate. METHODS: Medical history inquiry, clinical examination, Lake Louise
      scoring, and the collection of venous levels of bicarbonate concentration and
      base excess were performed on 52 lowland-dwelling persons after they completed a
      religious pilgrimage in the Nepal Himalayas to approximately 4,250 m. RESULTS:
      Oxygen saturation levels were strongly and inversely correlated with serum levels
      of venous bicarbonate and base excess, whereas AMS and Lake Louise scores were
      not associated with these measures of alkalosis. CONCLUSIONS: Our data suggest an
      association between measures of serum bicarbonate anion retention and decreasing
      oxygen saturation. Our data do not demonstrate an association between AMS or Lake
      Louise scores and measures of serum bicarbonate level. We propose that excessive
      hypoxemia at high altitudes may be associated with a compromised ability of the
      kidney to metabolically compensate for an altitude-induced hypocapnic alkalosis.

PMID- 16086893
TI  - Respiratory syndrome and respiratory tract infections in foreign-born and
      national travelers hospitalized with fever in Italy.
AB  - BACKGROUND: We measured frequency and epidemiologic, clinical, and hematochemical
      variables associated with respiratory tract infections (RTIs) in foreign-born and
      national patients hospitalized with fever with a history of international travel,
      and compared the final diagnosis of RTI with the presence of a respiratory
      syndrome (RS) at presentation. METHODS: A prospective, multicenter, observational
      study was conducted at tertiary care hospitals in Northern Italy from September
      1998 to December 2000. RESULTS: A final diagnosis of RTI was obtained in 40 cases
      (7.8%), 27 (67.5%) with lower RTI and 13 (32.5%) with upper RTI. The most common
      RTIs were pneumonia (35%) and pulmonary tuberculosis (15%). A white blood cell
      count > or = 10,000 and an erythrocyte sedimentation rate > or = 20 mm/h were
      independently associated with a final diagnosis of RTI; onset of symptoms at > or
      = 16 days and > or = 75% neutrophils were independently associated with lower
      RTI. An RS was identified in 51 (9.9%) of 515 travelers. Sensitivity,
      specificity, and positive and negative predictive values of a diagnosis of RS for
      a final diagnosis of RTI were 67.5%, 94.9%, 52.9%, and 97.2%, respectively.
      CONCLUSIONS: Pneumonia and pulmonary tuberculosis were frequent among foreign
      born and national travelers with fever admitted to a tertiary care hospital. Half
      of the pneumonia cases did not present with an RS at first clinical examination.

PMID- 16086894
TI  - Risk of travel-associated typhoid and paratyphoid fevers in various regions.
AB  - BACKGROUND: Although enteric fever (typhoid and paratyphoid fevers) is a major
      global public health problem, comparable data on the risks of contracting travel
      associated enteric fever in various regions of the world are scarce. METHODS:
      From the Swedish database on notifiable communicable diseases, we retrieved all
      case records from 1997 to 2003 on typhoid and paratyphoid fevers. The data set
      was compared with data on travel patterns obtained from a comprehensive travel
      database with information from interviews with more than 16,000 Swedish residents
      with recent overnight travel outside Sweden. RESULTS: The overall risk of being
      notified with enteric fever after travel was 0.42 in 100,000 travelers. The
      highest risk for typhoid fever was seen in travelers from India and neighboring
      countries (41.7 in 100,000), the Middle East (5.91 in 100,000), and Central
      Africa (3.33 in 100,000), whereas the risk was comparatively low in East Asia
      (0.24 in 100,000). Almost the same risk areas stood out for paratyphoid fever:
      India and neighbors (37.5 in 100,000), the Middle East (3.64 in 100,000), and
      East Africa (3.33 in 100,000). The epidemiology of paratyphoid fever was
      considerably affected by a large outbreak of paratyphoid B in a Turkish tourist
      resort in 1999. The youngest children were at highest risk for typhoid fever
      (odds ratio 44.2), whereas youths ages 7 to 18 years were at highest risk for
      paratyphoid fever (odds ratio 9.7). CONCLUSIONS: Detailed risk data for enteric
      fever after travel could form the basis for travel advice. Vaccination against
      typhoid fever should always be considered for travelers to the Indian
      subcontinent, the Middle East, and Africa but should not routinely be given to
      travelers to the Malay Peninsula.

PMID- 16086895
TI  - Drug abuse in travelers to southeast Asia: an on-site study.
AB  - BACKGROUND: Drug abuse constitutes a major sociomedical problem throughout the
      world. A unique subgroup with a higher potential of drug abuse are young
      travelers to Southeast Asia. Less than a handful of studies have focused on this
      population, and even fewer have been carried out on site. Our aim was to
      characterize the phenomenon of drug abuse among Israelis and other nationals, and
      to define risk factors that would predict which travelers are prone to abusing
      drugs. METHODS: Data was collected through questionnaires that were distributed
      in Southeast Asia to 430 travelers. Medical students administered the
      questionnaires across India, Thailand, Nepal, Vietnam, and Laos during 2002 and
      2003. RESULTS: Questionnaires from 231 Israelis and 199 other nationals (mostly
      from the United Kingdom, Sweden, Australia, and Germany) were analyzed. These
      travelers had a mean age of 25.3 years. We found that 54.3% of the travelers
      abused drugs during the trip. Israelis (66.2%) abused drugs more frequently than
      did non-Israelis (40.7%, p < .001). Males abused drugs significantly more than
      females did, as did secular more than religious people; however, those with an
      academic degree abused drugs less than others. For 23.5% of the Israelis, the
      trip was their first encounter with drugs. Of the entire cohort, 72% abused
      cannabis products, and most of them (49.6%) did it on daily basis. The use of
      "hard" drugs (eg, lysergic acid diethylamide) was more common among non-Israelis
      than among the Israelis (37% and 20%, respectively; p < .006). Much higher rates
      of drug abuse (70.1%) were found in India than in other Southeast Asian
      countries. Logistic regression identified that prior use of drugs, Israeli
      nationality, travel to India, cigarette smoking, and traveling alone were
      significant predictors of drug abuse. CONCLUSIONS: There is a disturbingly high
      rate of drug abuse in travelers to certain Southeast Asian countries, both among
      Israeli and other nationals. For many youngsters, this is their first encounter
      with drugs, and many plan to continue abusing drugs upon their repatriation.
      Travelers to Southeast Asia should be a major target group for primary,
      preventive, antidrug campaigns worldwide.

PMID- 16086896
TI  - Malaria prophylaxis for aircrew: safety of atovaquone/proguanil in healthy
      volunteers under aircraft cabin pressure conditions.
AB  - BACKGROUND: Because malaria in endemic areas presents a serious threat to the
      health of aircrew, optimal prevention is important. An effective and safe
      prophylactic antimalarial drug is needed. The combination of 250 mg atovaquone
      with 100 mg proguanil HCl (atovaquone/proguanil, or A/P) has shown good
      prophylactic efficacy and tolerance for prevention of falciparum malaria.
      However, medication for use by aircrew on duty is subject to approval by national
      and international aviation authorities, who require convincing evidence that the
      treatment has no negative effects on the flight performance of crews. The purpose
      of the present study was to evaluate the risk of detrimental effects of
      atovaquone/proguanil on flight-related performance and alertness in healthy
      subjects under conditions of aircraft cabin pressure. METHODS: A randomized,
      double-blind crossover study was conducted in which 24 subjects were enrolled to
      use A/P and placebo, each in a 14-day prophylactic dosing regimen with a 21-day
      washout phase. Vigilance, alertness, complex information processing, and
      sleepiness were assessed in a hypobaric chamber at 75.2 kPa, which equals the
      lower limit of commercial aircraft cabin pressure. Furthermore, duration and
      quality of sleep at home were recorded during the 14 days of drug administration.
      RESULTS: Twenty-two subjects completed the study. No significant differences were
      found between the effects of placebo and A/P on vigilance, alertness, complex
      information processing, sleep duration and quality, and the occurrence of adverse
      effects. CONCLUSIONS: In-flight performance and alertness of aircrew will not be
      affected by the prophylactic use of A/P during a period of 14 days.

PMID- 16086897
TI  - Who needs drug prophylaxis against malaria? My personal view.
AB  - A long tradition of successful malaria prophylaxis with chloroquine led to a
      dogma that drug prophylaxis should be given regardless of risk as soon as a
      traveler entered endemic areas. This prevailed also when resistance to
      chloroquine and adverse effects of alternatives became a problem. A cost/benefit
      analysis of the risk for malaria versus risk for adverse effects and cost of the
      recommended drug is not uniformly applied and drug prophylaxis is still advocated
      even when the risk for severe adverse effects greatly exceeds the risk for
      malaria, which is unethical.

PMID- 16086898
TI  - Imported malaria in an HIV-positive traveler: a case report with a fatal outcome.
AB  - We report a fatal case of malaria in an HIV-coinfected nonimmune traveler. The
      primary cause of death is discussed. The importance of prevention of malaria in
      nonimmune travelers is stressed. Prevention of malaria in nonimmune travelers
      should be regarded as a priority area for clinical practice and operational
      research.

PMID- 16086899
TI  - Cystic echinococcosis of the liver associated with repeated international travels
      to endemic areas.
AB  - Cystic echinococcosis (CE) is increasingly seen in immigrants from endemic areas
      to Western countries; however, it is rarely reported in short-term travels to
      endemic areas. This is partly because the echinococcal cyst typically grows
      slowly and may long remain clinically silent. We describe a case of cystic
      echinococcosis in a man born and living in a nonendemic urban area in North Italy
      that was acquired during a period of frequent travels in highly endemic
      countries.

PMID- 16086900
TI  - Nodular skin lesion in a returning traveler.
AB  - As tropical countries become common travelers' destinations, more and more
      returning travelers are expected to present with cutaneous lesions secondary to
      myiasis. The skin lesion starts as a small red papule and gradually enlarges to
      become a furuncle. Familiarity with the characteristic clinical presentation and
      proper management would avoid an unnecessary diagnostic work-up and therapeutic
      intervention, including surgery and the use of antibiotics.

PMID- 16086901
TI  - Acute subdural hemorrhage while traveling by bus: a risk factor in the elderly?
AB  - A 71-year-old man was delivered to our emergency department by an intercity bus.
      About 4 hours into a journey, he had complained of a headache to his wife. After
      one more hour, she noted a change in his level of alertness and notified the bus
      driver. A computed tomography scan of the head showed a subdural hemorrhage.

PMID- 16086902
TI  - Air travel and cardiovascular disease.

PMID- 16086906
TI  - Comparison of end normal inspiration and expiration for gated intensity modulated
      radiation therapy (IMRT) of lung cancer.
AB  - BACKGROUND AND PURPOSE: Gated delivery of radiation during part of the
      respiration cycle may improve the treatment of lung cancer with intensity
      modulated radiation therapy (IMRT). In terms of the respiration phase for gated
      treatment, normal end-expiration (EE) is more stable but normal end-inspiration
      (EI) increases lung volume. We compare the relative merit of using EI and EE in
      gated IMRT for sparing normal lung tissue. PATIENTS AND METHODS: Ten patients
      received EI and EE respiration-triggered CT scans in the treatment position. An
      IMRT plan for a prescription dose of 70 Gy was generated for each patient and at
      each respiration phase. The optimization constraints included target dose
      uniformity, less than 35% of the total lung receiving 20 Gy or more and maximum
      cord dose <or=45 Gy. We compared planning target volume (PTV) coverage, mean lung
      dose, percentage of total lung receiving 20 Gy or more (V(20)) and lung normal
      tissue complication probability (NTCP). RESULTS: For 9 of the 10 patients, cord
      and lung doses were acceptable and PTV coverage was similar for EE and EI, with
      lung sparing was equal to or slightly better at EI than at EE. For the 10th
      patient, lung sparing at EI was significantly better. Patient averaged mean lung
      dose was 15.4 Gy (range: 7.1-20.4) at EI and 16.3 Gy (range: 6.9-21.9) at EE. The
      average V(20) was 23.8% (range: 13-36.4) at EI and 25.3% (range: 13-37.3) at EE.
      The average NTCP at EI was 8 versus 12% at EE. CONCLUSIONS: Dosimetric indices of
      lung protection for IMRT plans at EI are better than at EE. For 9 out of the 10
      patients in our study, this difference is small. Thus other factors such as
      reproducibility, reliability and duty cycle at normal end expiration may be more
      critical for selecting treatment breathing phase.

PMID- 16086907
TI  - Radiotherapy planning for lung cancer: slow CTs allow the drawing of tighter
      margins.
AB  - BACKGROUND AND PURPOSE: Evaluation of the use of planning CTs with slow
      revolution time (4s/slice; 'slow CTs') in the planning procedure of radiotherapy
      for lung cancer patients in comparison to commonly used 'fast' planning CTs;
      impact on margin assessment of planning target volume (PTV) design. PATIENTS AND
      METHODS: Eighteen lung cancer patients (six upper, lower lobe and central tumors,
      respectively) have been scanned each by three series of slow CTs and one fast CT
      (spiral CT). Patients have been freely breathing. The largest transversal tumor
      diameters in slow and fast CTs have been measured. Tumor edge positions have been
      determined for six spatial directions in all slices of the three slow CT series.
      RESULTS: Slow CTs show larger dimensions of the visible tumor than fast CTs. The
      median difference of the diameter for all tumors is 2mm (range 0-4mm). Slow CTs
      deliver constant depictions of lung tumors within a range of 1.6mm in all
      directions. This margin is considered to be sufficient to compensate for tumor
      movements by respiration and cardiovascular motions (internal margin). A margin
      of 7 mm added to the GTV of a single slow CT series to draw the PTV is proposed.
      CONCLUSIONS: Slow planning CTs show larger, but highly constant depictions of
      lung tumors in comparison to conventional fast CT scanning, yielding an integral
      delineation of almost all positions of the moving tumors. Thus the use of slow
      planning CTs enables the drawing of tighter margins in external beam treatment
      planning of lung cancer.

PMID- 16086908
TI  - Concomitant boost radiotherapy with concurrent weekly cisplatin in advanced head
      and neck cancers: a phase II trial.
AB  - BACKGROUND AND PURPOSE: To determine the safety and efficacy of concomitant boost
      radiotherapy (CBRT) with concurrent cisplatin chemotherapy (CT) in advanced head
      and neck cancers. PATIENTS AND METHODS: Between February 2000 and June 2001, 95
      previously untreated patients of advanced head and neck cancers were treated with
      CBRT and concurrent cisplatin CT. CBRT consisted of: phase I--44 Gy/22fx/4.5
      weeks, phase IIa--16 Gy/8fx/1.5 weeks and phase IIb--10 Gy/8fx (delivered as a
      second daily fraction after a gap of 6h along with phase IIa). CT (cisplatin 35
      mg/m(2)) was administered weekly usually preceding CBRT by an hour. RESULTS: The
      median follow-up was 39 months (range 8-50 months). CBRT compliance (70 Gy in 40
      44 days) was seen in 66% (63/95). Six cycles of CT was delivered in 73% (69/95).
      Acute grade III/IV mucosal toxicity was seen in 79% and resulted, on average, in
      a total weight loss of 7.9 kg from a mean pretreatment weight of 51 kg.
      Nasogastric tube placements were required in 26% (25/95) for an average duration
      of 19.3 days. Grade III leucopenia was seen in 2%. Mortality during and within 30
      days of treatment was seen in 14% (13/95). Crude incidence of late subcutaneous
      fibrosis (grade III) was 21% (12/57) and a case of mandibular necrosis and
      thyroid cartilage necrosis each were seen. Initial loco regional disease
      clearance was seen in 59% (56/95) and the Kaplan-Meier estimates of 3-year loco
      regional control rate and overall survival were 25% (median 7 months, 95% C.I. 3
      11) and 27% (median 12 months, 95% C.I. 8-16), respectively. CONCLUSIONS: On
      present evidence, in the settings of a developing country, CBRT with concurrent
      cisplatin cannot be recommended as primary therapy in advanced head and neck
      cancers without formal comparison with other treatment modalities.

PMID- 16086909
TI  - Paclitaxel, cisplatin, 5-fluorouracil and radiotherapy in the management of
      advanced squamous cell carcinoma of the head and neck: a phase II trial.
AB  - Aim of the present study was to test, activity and toxicity of a rapidly
      alternating chemoradiation (paclitaxel based) in 31 patients with unresectable,
      locally advanced or recurrent after surgery, head and neck cancer. Three-year
      overall survival and progression-free survival were 61.4 and 73.7%, respectively.
      Main side effects remain a major problem.

PMID- 16086910
TI  - Towards equity in turbulent Europe ESTRO, European cooperation and the European
      Commission.

PMID- 16086911
TI  - The bright but ephemeral life of a rainbow: a chronicle of seventeen years of
      intensive ESTRO-EU cooperation.

PMID- 16086912
TI  - 20 Gy versus 44 Gy supplemental beam radiation with Pd-103 prostate
      brachytherapy: preliminary biochemical outcomes from a prospective randomized
      multi-center trial.
AB  - BACKGROUND AND PURPOSE: While favorable results are achieved with combined
      modality irradiation, there has never been a rigorous study of the need for
      supplemental beam. The study reported here compares clinical outcomes with
      substantially different external beam radiation doses. Similar to classic
      randomized Wilm's tumor studies from the 1980s, the intention of the trial design
      was to decrementally test the need for beam radiation. PATIENTS AND METHODS: As
      of June 2000, 165 of a planned 600 patients with 1997 AJC clinical stage T1c-T2a
      prostatic carcinoma, Gleason grade 7-10 and/or PSA 10-20 ng/ml, were treated on a
      randomized protocol comparing 44 versus 20 Gy pre-implant supplemental beam
      radiation, combined with Pd-103, 90 versus 115 Gy, respectively (NIST-1999).
      Freedom from biochemical failure was defined as a serum PSA</=0.5 ng/ml at last
      follow-up. Patients were censored at last follow-up if their serum PSA was still
      decreasing. Patients whose serum PSA nadired at a value >0.5 ng/ml were scored as
      failures at the time at which their PSA nadired. The follow-up period for non
      failing patients ranged from 0.5 to 4.9 years (median: 2.9 years). Accrual of 566
      patients was achieved in October 2004. The study was closed at that time because
      of slowing accrual, due in part to the findings reported here. RESULTS: The
      overall actuarial freedom from biochemical progression at 3 years is 85%, with 59
      patients followed beyond 3 years. A total of 21 patients have developed
      biochemical failure, 12 treated with 20 Gy and nine treated with 44 Gy. There
      were no clinically evident local failures. The actuarial biochemical freedom-from
      failure rate at 3 years was 83% for 20 Gy patients versus 88% for 44 Gy patients
      (P=0.64). For 112 patients with a pre-treatment PSA<10 ng/ml, the 3-year freedom
      from progression was 84% in patients receiving 20 Gy beam radiation versus 94% in
      those who received 44 Gy beam (P=0.16). For 47 patients with a pre-treatment
      PSA>10 ng/ml, the 3-year freedom from progression was 82% in patients receiving
      20 Gy beam radiation versus 72% in those who received 44 Gy beam (P=0.38).
      CONCLUSIONS: The randomized data presented here suggests that the likelihood of
      biochemical cure is similar with standard (44 Gy) or lower dose (20 Gy)
      supplemental beam radiation. Since the biological effect of 20 Gy external beam
      radiation is likely to be small, we interpret these preliminary results to
      suggest that supplemental beam radiation is unnecessary, in the setting of a high
      degree of prostate coverage by the brachytherapy prescription dose. With closure
      of this study, we have begun treating intermediate and high risk patients on a
      prospective randomized comparison of Pd-103 with 20 versus 0 Gy supplemental beam
      radiation.

PMID- 16086913
TI  - Anatomy-based inverse planning dose optimization in HDR prostate implant: a
      toxicity study.
AB  - BACKGROUND AND PURPOSE: The aim of this study is to evaluate the acute and late
      complications in patients who have received HDR implant boost using inverse
      planning, and to determine dose volume correlations. PATIENTS AND METHODS:
      Between September 1999 and October 2002, 44 patients with locally advanced
      prostate cancer (PSA>/=10 ng/ml, and/or Gleason score>/=7, and/or Stage T2c or
      higher) were treated with 40-45 Gy external pelvic field followed by 2--3
      fraction of inverse-planned HDR implant boost (6--9.5 Gy /fraction). Median
      follow-up time was 1.7 years with 81.8% of patients who had at least 12 months of
      follow up (range 8.6--42.5. Acute and late morbidity data were collected and
      graded according to RTOG criteria. Questionnaires were used to collect prostate
      related measures of quality of life, and international prostate symptom score
      (IPSS) before and after treatment. Dose-volume histograms for prostate, urethra,
      bladder, penis bulb and rectum were analyzed. RESULTS: The median patient age was
      64 years. Of these, 32% were in the high risk group, and 61% in the intermediate
      risk group. 3 patients (7%) had no adverse prognostic factors. A single grade 3
      GU acute toxicity was reported but no grade 3--4 acute GI toxicity. No grade 3--4
      late GU or GI toxicity was reported. Acute (late) grade 2 urinary and rectal
      symptoms were reported in 31.8 (11.4%) and 4.6% (4.6%) of patients, respectively.
      A trend for predicting acute GU toxicity is seen for total HDR dose of more than
      18 Gy (OR=3.6, 95%CI=[0.96--13.5], P=0.058). The evolution of toxicity is
      presented for acute and late GU/GI toxicity. Erectile dysfunction occurs in
      approximately 27% of patients who were not on hormonal deprivation, but may be
      taking sildenafil. The IPSS peaked on averaged 6 weeks post-implant and returned
      to the baseline at a median of 6 months. CONCLUSIONS: Inverse-planned HDR
      brachytherapy is a viable option to deliver higher dose to the prostate as a
      boost without increasing GU or rectal complication. Further HDR dose escalation
      to the prostate is feasible.

PMID- 16086914
TI  - Phase II study of vitamin E and pentoxifylline in patients with late side effects
      of pelvic radiotherapy.
AB  - BACKGROUND AND PURPOSE: Radiation-induced tissue fibrosis is a common adverse
      effect of curative treatment for pelvic cancer. Pilot studies testing alpha
      tocopherol and pentoxifylline provide evidence of clinical regression of
      superficial radiation fibrosis after radiotherapy. PATIENTS AND METHODS: Twenty
      seven eligible research volunteers with a minimum of one grade 3 or 4 disability
      (LENT SOMA) due to previous radiotherapy were entered into the study. Volunteers
      were given dl-alpha tocopheryl acetate 500 mg twice a day orally plus
      pentoxifylline 400mg twice a day orally over a period of 6 months. Clinical
      assessment of late side effects recorded using LENT SOMA scales was selected as
      the primary endpoint, taken at baseline and at 6 and 12 months post-registration.
      Patient self-assessment of function and quality of life was assessed as a
      secondary endpoint using the EORTC QLQ-C30 core questionnaire and the EORTC QLQ
      CR38 pelvic module. Magnetic resonance imaging was undertaken in 13/23 evaluable
      volunteers before and after 6 months of therapy. RESULTS: At 12 months post
      registration there were 4 out of 23 responders. At 6 months post-registration
      there was a statistically significant improvement (i.e. reduction) in the median
      of the LENT SOMA summed scores in all areas assessed apart from 'male sexual
      dysfunction', 'vulva' and 'vagina' which were unchanged at 6 months. The median
      total LENT SOMA score at baseline and 6 months was 49 and 34, respectively, with
      a median change in total LENT SOMA score between baseline and 6 months of 9 (IQR
      7-18) (P<0.001). The maximum LENT SOMA scores improved over the study period,
      with a total number of 82 maximum grade 3 or 4 normal tissue scores at baseline
      (median of four complications per person) reduced to a total number of 67 maximum
      grade 3 or 4 scores at 6 months post-registration (median of 3 complications per
      person), i.e. a median reduction in severe complications of one per person. LENT
      SOMA scores at 12 months were similar to those observed at 6 month suggesting no
      further improvement nor deterioration in late side effects. These findings were,
      however, not reflected in the patient self-assessment of function and quality of
      life, raising question about the possibility of observer bias in recording LENT
      SOMA scores. No significant changes were reported on magnetic resonance images at
      6 months from baseline. CONCLUSIONS: Despite only seeing four a priori defined
      responders in this pilot study testing dl-alpha tocopheryl acetate plus
      pentoxifylline in patients suffering complications of pelvic radiotherapy,
      changes in LENT SOMA scores suggest beneficial effects. However, we are not
      convinced that these effects are real, since no significant changes in symptoms
      and functional status were recorded by detailed prospective patient self
      assessments.

PMID- 16086915
TI  - Towards evidence-based guidelines for radiotherapy infrastructure and staffing
      needs in Europe: the ESTRO QUARTS project.
AB  - BACKGROUND AND PURPOSE: Adequate and equitable access to radiotherapy (RT) must
      be a reasonable health care goal for the EU. However, there are large variations
      among the EU countries and even regional variations within countries in the
      provision of RT. In this report, we combine the best available evidence on the
      indications for RT with national epidemiological data to arrive at estimates for
      the appropriate level of RT infrastructure in the 25 EU countries. PATIENTS AND
      METHODS: Data from three systematic overviews of the best available evidence for
      the indication for RT in 23 main cancer types are combined with epidemiological
      data from the EUCAN and GLOBOCAN databases on the crude incidence of each of
      these cancers in the 25 EU countries. Together with published benchmarks for
      accelerator throughput this allows estimation of the number of linear
      accelerators per million people required to facilitate appropriate RT utilization
      rates in each country. Where possible, the estimates are compared with the
      detailed data available from Sweden. RESULTS: The crude incidence of the main
      cancer types shows large variation among the 25 EU countries. This reflects in
      part differences in exposure to aetiological risk factors and partly differences
      among the countries in population age structure. Correspondingly, the estimate of
      the required number of linear accelerators per million people showed considerable
      variation: ranging from 4.0 in Cyprus to 8.1 in Hungary. The average for the 25
      countries was 5.9 per million people. These estimates were compared with
      available national guidelines and actual data on RT infrastructure and large
      shortfalls were found in many countries. Implications for health economics and
      capacity planning are briefly discussed. CONCLUSIONS: The QUARTS project has
      developed a model that establishes a direct and transparent link between
      epidemiological data and indications for RT based on the best available evidence.
      Comparison of the model estimates with current levels of RT infrastructure has
      revealed major inequalities in provision of RT in the 25 EU countries.
      Continuation of this study is recommended as a way of improving RT provision on
      rational grounds throughout the European community and as a model for health care
      planning in the EU.

PMID- 16086916
TI  - The vulnerable endothelium: priming the vascular endothelium for thrombosis with
      unfractionated heparin: biologic plausibility for observations from the Superior
      Yield of the New Strategy of Enoxaparin, Revascularization and GlYcoprotein
      IIb/IIIa Inhibitors (SYNERGY) trial.

PMID- 16086917
TI  - Biopsychosocial experiences of adults with congenital heart disease: review of
      the literature.
AB  - BACKGROUND: Approximately 1% of all newborns display some form of congenital
      heart disease (CHD). Successful medical and surgical management of CHD has
      allowed 85% of these children to survive into adulthood and produced a new set of
      challenges for both patients and doctors with an emphasis on quality of life and
      psychosocial functioning. METHODS: The current paper has 3 aims: (1) to summarize
      the research literature examining the emotional adjustment among this population,
      (2) to detail the psychological, social, and quality-of-life factors that might
      result in an increased risk of psychological maladjustment, and (3) to provide
      clinical management strategies to optimize health outcomes. RESULTS: Current
      empirical evidence has suggested that compared with same aged reference norms in
      US studies, adults with CHD had scores indicative of worse emotional functioning
      as assessed by both clinical interviews and self-report measures. Similar
      European studies have generally not demonstrated such differences. Additional
      research suggests that areas of functioning that may be particularly affected
      include neurocognitive functioning, body image, social and peer relationships,
      and mild delays in developmental functioning. CONCLUSIONS: These studies suggest
      that patients with CHD are successfully engaging in full adult responsibilities
      and roles but do experience specific psychosocial challenges that may impact
      emotional functioning, self-perception, and peer relationships. Lifestyle
      considerations in young adulthood are significant and impinge on pregnancy
      considerations and exercise capabilities. Clinical management strategies include
      increased awareness and dialogue between patients with CHD and physicians
      regarding psychosocial concerns.

PMID- 16086918
TI  - Methodological design for economic evaluation in Public Access Defibrillation
      (PAD) trial.
AB  - OBJECTIVE: Our objective is to describe the rationale and methods for the
      economic analysis of the PAD trial. The objective of this analysis is to assess
      whether automated external defibrillators (AEDs) use by lay responders is good
      value for money. METHODS: Design. This economic evaluation is being conducted
      concurrently with a randomized trial of (a) control--training to recognize
      arrest, access 911, and administer cardiopulmonary resuscitation (CPR) while
      awaiting arrival of emergency medical services providers versus (b) intervention-
      training to recognize arrest, access 911, administer CPR, and use an AED while
      awaiting emergency medical services providers. Lay responders in either group
      were trained to deliver the study intervention. Population. Participating sites
      identified distinct units with a population of at least 250 people aged > or = 50
      years. Outcome. The primary economic outcome is the incremental cost
      effectiveness ratio of intervention versus control. RESULTS: Nine hundred ninety
      three units including 1260 public and residential locations were randomized.
      There were 30 survivors in the intervention group and 15 in the control group (P
      = .03). Sampling will identify program and health care costs. A societal
      perspective will be adopted. Incremental cost effectiveness will be estimated by
      using bootstrapping and decision analytic modeling. CONCLUSION: The study will
      demonstrate whether defibrillation by lay responders improves outcomes at
      reasonable cost. If so, then the thousands of lives will be improved annually. If
      not, then limited resources can be invested in other interventions. Our methods
      also provide a framework for economic evaluations of other interventions for
      acute cardiovascular events.

PMID- 16086919
TI  - Blood glucose: a strong risk factor for mortality in nondiabetic patients with
      cardiovascular disease.
AB  - BACKGROUND: The prognostic significance of blood glucose (BG) for nondiabetic
      patients in a stable chronic phase of cardiovascular disease (CVD) has been
      sparsely investigated, especially for glucose within the normal range. In
      particular, it is unknown if for these patients there is a graded relation of
      mortality to glucose or if there is a lower threshold. METHODS: We used the
      Framingham Heart Study 30-year data to determine 2-year all-cause, cardiovascular
      mortality (CVM), and non-CVM risk adjusted for age, sex, and typical
      cardiovascular risk factors (systolic blood pressure, total cholesterol, body
      mass index, cigarette smoking, and use of antihypertensive drugs) by levels of
      random whole BG for non-glucose-intolerant subjects (glucose intolerance includes
      diabetes mellitus) with existing CVD. RESULTS: There were steep graded relations
      of 2-year all-cause, CVM, and non-CVM to BG throughout the normal and subdiabetic
      range with no evidence of a lower threshold. Two-year mortality continuously
      increased from 2.99% at the bottom of the normal range (BG = 60 [plasma
      equivalent = 67] mg/dL) to 7.23% at the top of the normal range (89 [plasma
      equivalent = 100] mg/dL) (a 2.42-fold increase) and then continued to further
      continuously increase, reaching 11.38% at 119 [plasma equivalent = 133] mg/dL,
      the top of the glucose range considered (P for trend < .0001). There were
      analogous steep increases for CVM and non-CVM. CONCLUSIONS: Blood glucose, even
      within the normal range, is a strong independent predictor of 2-year all-cause,
      CVM, and non-CVM in nondiabetic subjects with CVD and therefore of prognostic
      significance for these high-risk patients.

PMID- 16086920
TI  - Left ventricular ejection fraction to predict early mortality in patients with
      non-ST-segment elevation acute coronary syndromes.
AB  - BACKGROUND: Improvement in risk stratification of patients with non-ST-segment
      elevation acute coronary syndrome (ACS) is a gateway to a more judicious
      treatment. This study examines whether the routine determination of left
      ventricular ejection fraction (EF) adds significant prognostic information to
      currently recommended stratifiers. METHODS: Several predictors of inhospital
      mortality were prospectively characterized in a registry study of 1104
      consecutive patients, for whom an EF was determined, who were admitted for an
      ACS. Multiple regression models were constructed using currently recommended
      clinical, electrocardiographic, and blood marker stratifiers, and values of EF
      were incorporated into the models. RESULTS: Age, ST-segment shifts, elevation of
      cardiac markers, and the Thrombolysis in Myocardial Infarction (TIMI) risk score
      all predicted mortality (P < .0001). Adding EF into the model improved the
      prediction of mortality (C statistic 0.73 vs 0.67). The odds of death increased
      by a factor of 1.042 for each 1% decrement in EF. By receiver operating curves,
      an EF cutoff of 48% provided the best predictive value. Mortality rates were 3.3
      times higher within each TIMI risk score stratum in patients with an EF of 48% or
      lower as compared with those with higher. CONCLUSIONS: The TIMI risk score
      predicts inhospital mortality in a broad population of patients with ACS. The
      further consideration of EF adds significant prognostic information.

PMID- 16086921
TI  - A randomized trial comparing clopidogrel versus ticlopidine therapy in patients
      undergoing infarct artery stenting for acute myocardial infarction with abciximab
      as adjunctive therapy.
AB  - AIM: To evaluate the impact of a clopidogrel therapy on the effectiveness of
      myocardial reperfusion in patients with ST-segment elevation acute myocardial
      infarction (AMI) undergoing routine infarct-related artery (IRA) stent
      implantation and receiving routine abciximab therapy. BACKGROUND: Inflammatory
      processes after mechanical restoration of flow in AMI play a central role in
      decreasing the effectiveness of reperfusion at microcirculatory level. Several
      studies suggest that clopidogrel may exert a protective effect against adverse
      cardiovascular events by virtue of its anti-inflammatory properties. METHODS: A
      total of 133 patients with a first ST-elevation AMI were randomized to
      clopidogrel (600-mg loading dose before IRA stenting followed by 75 mg daily, n =
      66) or ticlopidine (500 mg before IRA stenting followed by 250 mg twice daily, n
      = 67). The primary end point was scintigraphic infarct size at 1 month. The
      secondary end points were ST-segment elevation resolution within 3 hours of
      procedure and 1-month clinical outcome, as a composite of death, reinfarction,
      target vessel revascularization, and stroke within 1 month of the index
      procedure. RESULTS: The 1-month technetium 99m sestamibi scintigraphy revealed
      similar infarct size (16.2% +/- 14.6% vs 15.0% +/- 14.1%, P = .703) and severity
      (0.48 +/- 0.18 vs 0.49 +/- 0.15, P = .592) in the clopidogrel group as compared
      with the ticlopidine group. Three-hour ST-segment resolution rate was similar in
      the 2 study groups (86% vs 89%, P = .642). At 1 month, there was no difference in
      major cardiovascular adverse event rate (3% vs 3%, P = .988). Discontinuation of
      thienopiridine therapy within the first month occurred in no patient randomized
      to clopidogrel and in 3 (4.5%) patients randomized to ticlopidine (P = .082).
      CONCLUSION: Clopidogrel has no impact on the effectiveness of myocardial
      reperfusion in patients with AMI treated routinely with stenting and abciximab.
      However, clopidogrel, administered as a 600-mg loading dose followed by 75 mg
      daily, is safe and at least as effective as the standard ticlopidine therapy in
      this subgroup of patients.

PMID- 16086922
TI  - Heart disease epidemic in Pakistan: women and men at equal risk.
AB  - OBJECTIVE: We conducted this study to determine the prevalence of coronary artery
      disease (CAD) and its risk factors in Karachi, Pakistan. BACKGROUND: Migrant
      South Asians residing in the West have one of the highest rates of CAD in the
      world. Estimates of disease in nonmigrant populations are conflicting. METHODS:
      We conducted a population-based cross-sectional survey on 320 randomly selected
      adults aged > or = 40 years. Coronary artery disease was defined as the composite
      outcome of (1) abnormalities indicative of definite or probable CAD based on the
      Minnesota classification of electrocardiogram or (2) past history of heart
      attack. RESULTS: The overall prevalence of CAD (95% CI) was 26.9% (22.3%-32.0%):
      23.7% (17.8%-30.9%) in men vs 30.0% (23.4-37.5%) in women (P = .12). Risks did
      not differ substantially by age group. The factors (odds ratio, 95% CI)
      independently associated with CAD were current tobacco use (2.12, 1.21-3.73),
      systolic blood pressure (1.08, 1.02-1.15, for each 5 mm Hg increase), and
      proteinuria (2.49, 1.04-5.95). Coronary artery disease odds for women vs men
      (1.38, 0.84-2.62) increased to 1.60 (0.93-2.75), when adjusted for key risk
      factors. CONCLUSIONS: One in 4 middle-aged adults in Pakistan has prevalent CAD.
      Risks are uniformly high in the young and in women. Concerted efforts are needed
      to prevent the epidemic of cardiovascular disease in South Asia, focusing on
      hypertension, diabetes, smoking, and dyslipidemia.

PMID- 16086923
TI  - Association between cardiac troponin T elevation and angioscopic morphology of
      culprit lesion in patients with non-ST-segment elevation acute coronary syndrome.
AB  - BACKGROUND: It is well known that cardiac troponin T (TnT) elevation on admission
      indicates a high-risk subgroup among patients with non-ST-segment elevation acute
      coronary syndrome (NSEACS). Although the mechanism of TnT elevation is speculated
      to be the microthromboembolism from unstable plaques, it has not been clarified.
      The aim of this study is to clarify the association between the serum TnT
      elevation and the angioscopically evaluated morphology of culprit lesion in the
      patients with NSEACS. METHODS: Among 113 patients with NSEACS who had significant
      coronary stenosis, 62 patients with successful angioscopic examination were
      prospectively and consecutively enrolled from October 2001 to August 2002.
      Patients were divided into 2 groups according to the serum TnT level measured
      before percutaneous coronary intervention: TnT-positive or TnT-negative group.
      Thrombus and plaque color at culprit lesion were evaluated by angioscopy and were
      compared between the groups. Plaque color was determined as yellow or white, and
      thrombus as none, small, or large. Three different definitions for TnT-positive
      (> or =0.1, > or =0.03, and > or =0.01 ng/mL) were used and the sensitivity and
      specificity for detecting thrombus was compared. RESULTS: Prevalence of thrombus,
      large thrombus, and yellow plaque were all higher in TnT-positive than in TnT
      negative group for 3 different cutoff values of TnT. Angiographic slow-flow
      occurred more frequently after percutaneous coronary intervention in TnT-positive
      than in TnT-negative group for 3 different cutoff values of TnT.
      Sensitivity/specificity of detecting large thrombus were 33%/100%, 44%/91%, and
      56%/83% when TnT-positive was defined as TnT > or = 0.1, > or =0.03, and > or
      =0.01 ng/mL, respectively. CONCLUSIONS: Serum TnT level was significantly
      associated with the prevalence of thrombus and yellow plaque at the culprit
      lesions of NSEACS. Troponin T, when positive was defined as > or =0.01 ng/mL,
      still have a high specificity for detecting intracoronary thrombus.

PMID- 16086924
TI  - Symptoms and type of symptom onset in acute coronary syndrome in relation to ST
      elevation, sex, age, and a history of diabetes.
AB  - BACKGROUND: Various efforts to reduce patient delay in acute coronary syndrome
      (ACS) have had limited success. One reason might be a misinterpretation of the
      symptoms of ACS. The aim of this study was therefore to explore the
      characteristics and severity of symptoms among patients with an ACS in overall
      terms and in relation to the type of ACS, sex, age, and diabetes. METHODS: A
      total of 1939 patients at 11 hospitals in Sweden answered a questionnaire
      containing questions relating to the localization and intensity of symptoms, the
      presence of associated symptoms, the characteristics and experience of
      pain/symptoms, and the type of symptom onset. RESULTS: Patients with ST elevation
      differed from those without by more frequently having associated symptoms. They
      had higher pain/discomfort intensity and more frequently had pain with abrupt
      onset reaching maximum intensity within minutes. However, this type of symptom
      onset was only seen in less than half the patients with ST elevation and only 1
      in 5 fulfilled all the criteria usually associated with a severe heart attack.
      Women differed from men in a few respects. They more frequently reported
      pain/discomfort in the neck or jaw and back, vomiting, and scored their
      pain/discomfort slightly higher than men. Differences between age groups were
      minor and there was no difference between patients with and without diabetes.
      CONCLUSIONS: The most striking finding was the low proportion of patients with
      the type of symptoms that are commonly associated with ACS. This is important for
      the planning of educational campaigns/programs to reduce patient delay.

PMID- 16086925
TI  - Candidate gene susceptibility variants predict intermediate end points but not
      angiographic coronary artery disease.
AB  - BACKGROUND: Moderate-sized studies have suggested that variants of candidate
      genes can influence laboratory markers of coronary artery disease (CAD), but
      whether they predict parallel changes in clinical CAD risk is unknown. METHODS:
      We studied a single nucleotide polymorphism (SNP) from each of the 5 candidate
      genes for intermediate (laboratory) and clinical (angiographic CAD) end points in
      a large cohort of patients. The 5 gene SNPs were cholesteryl ester transfer
      protein (CETP) TaqIB (N = 3219), ATP-binding cassette (ABCA1) G596A (N = 3302),
      lipoprotein lipase (LPL) HindIII (N = 909), plasminogen activator inhibitor, type
      1 (PAI1), 4G/5G (N = 1142), and hepatic lipase (HL) C-541T (N = 4704).
      Intermediate outcomes were high-density lipoprotein cholesterol (HDL-C) and
      triglycerides (TGs). Cases had 1- to 3-vessel CAD (> or = 70% stenosis); controls
      had angiographically normal coronaries. RESULTS: Cholesteryl ester transfer
      protein predicted HDL (mean, B1B1 35.0 mg/dL, B2B2 38.6 mg/dL; P < .001) but not
      CAD (B1B1 74%, B2B2 70%; adjusted P = .35, odds ratio [OR] = 0.89). ABCA1
      predicted HDL (mean, GG = 36.4 mg/dL, AA = 39.2 mg/dL; P = .02) but not CAD (GG
      74%, AA 75%; adjusted P = .96, OR = 0.99). HL predicted HDL (CC 37.1 mg/dL, TT
      40.9 mg/dL; P = .002) but not CAD (CC 71%, TT 68%, adjusted P = .66, OR = 0.94).
      LPL predicted TG (median: [++] 134, [--] 98 mg/dL; P < .001) but not CAD ([++]
      79%, [--] 79%; adjusted P = .99, OR = 1.00). PAI1 predicted TG (median, 4G4G 130
      mg/dL, 5G5G 148 mg/dL; P = .16), but not CAD (4G4G 77%, 5G5G 76%; adjusted P =
      .62, OR = 1.11). CONCLUSIONS: Five SNPs predicted differences in risk-related
      lipids but not angiographic CAD. These discrepancies suggest that genetic
      determinants of CAD are complex and intermediate phenotypes are poor surrogates.
      These findings have important implications for future directions in genetic
      research.

PMID- 16086926
TI  - Reproducibility of nitrate-stimulated tilt testing in patients with suspected
      vasovagal syncope and a healthy control group.
AB  - OBJECTIVE: Nitrate-stimulated tilt testing may be used to diagnose vasovagal
      syncope or to guide therapy. To date, the reproducibility of the test in patients
      with clinically suspected vasovagal syncope and healthy controls is undetermined.
      A high reproducibility is a prerequisite for correct interpretation of the test
      result. This study investigates the reproducibility of a nitrate-stimulated tilt
      test in patients with clinically suspected vasovagal syncope and a healthy
      control group. METHODS AND RESULTS: We studied 43 patients (24 women, 19 men)
      with a typical history of vasovagal syncope and 18 healthy controls (3 women, 15
      men). We used a combined tilt protocol with a 30-minute passive and 15-minute
      nitrate-stimulated phase. The second tilt test was performed 16 +/- 12 days after
      the first. In both patients and controls, overall positive tilt responses were
      reproduced in the second test in 100%. In contrast to this, the reproducibility
      of an overall negative test was 50% in patients but 93% in controls. Overall
      hemodynamic responses to tilt were reproducible in 80%. CONCLUSION: Nitrate
      stimulated tilt testing in both patients with suspected vasovagal syncope and
      controls has an excellent reproducibility of positive results but a moderate
      reproducibility of negative results. Importantly, these results are still valid
      at a repeat interval of 2 weeks and longer. These data suggest that in patients
      with suspected vasovagal syncope, a nitrate-stimulated tilt test may provide a
      suitable tool to evaluate the efficacy of a therapeutic approach.

PMID- 16086927
TI  - Effect of angiotensin-converting enzyme or vasopeptidase inhibition on
      ventricular size and function in patients with heart failure: the Omapatrilat
      Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE)
      echocardiographic study.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition attenuates ventricular
      remodeling and improves ventricular function in heart failure patients.
      Vasopeptidase inhibition has shown similar effects in experimental models.
      OBJECTIVES: The OVERTURE echocardiographic study was designed to test the
      hypothesis that the vasopeptidase inhibitor omapatrilat would attenuate
      ventricular remodeling and improve ventricular function to a greater extent than
      an ACE inhibitor. METHODS: Three hundred twenty-one patients with heart failure
      (New York Heart Association class > or = 2) were included in the OVERTURE
      echocardiographic substudy and were randomized to receive enalapril (10 mg twice
      a day) or omapatrilat (40 mg every day). Echocardiograms were performed at
      baseline and at 1 year (n = 214). Left ventricular size was estimated by
      summation of ventricular areas in apical and short-axis views and by calculation
      of ventricular volumes. Ejection fraction was calculated from ventricular
      volumes. RESULTS: Combined diastolic and systolic areas and volumes decreased
      significantly (mean diastolic area change -8.36 cm2, 95% CI -9.4 to -7.3 cm2;
      mean systolic change -8.4 cm2, 95% CI -9.5 to -7.3 cm2), and ejection fractions
      increased significantly (3.6%, 95% CI 2.6% to 4.6%) in both treatment groups from
      baseline to 1 year. There were no differences in the magnitude of improvement in
      ventricular size or function based on treatment assignment. Patients who died or
      were hospitalized for heart failure subsequent to the final assessment
      demonstrated the least degree of reverse remodeling. CONCLUSION: Ventricular size
      and function improved similarly after 1 year with ACE or vasopeptidase inhibition
      in patients with heart failure. Reverse remodeling was associated with improved
      outcome.

PMID- 16086928
TI  - Impact of pregnancy-related heart failure on humoral immunity: clinical relevance
      of G3-subclass immunoglobulins in peripartum cardiomyopathy.
AB  - BACKGROUND: The impact and clinical relevance of pregnancy-related heart failure
      (HF) on humoral immunity are not known. Heart failure is often characterized by
      immunoglobulins (Ig) that differ in subclass profile with etiology. Subclass
      immunoglobulins differ in the biologic information they confer in disease.
      Therefore, given that progressive gestation is associated with immunologic
      incompetence, we sought to study the relative impact of pregnancy-related onset
      of HF on humoral immunity. METHODS: Immunoglobulins (class G and subclasses G1,
      G2, G3) against cardiac myosin were evaluated in 47 patients with peripartum
      cardiomyopathy (PPCM) from different global regions: South Africa (n = 15),
      Mozambique (n = 9), and Haiti (n = 23) and compared with healthy mothers and
      patients with idiopathic dilated cardiomyopathy (DCM). C-reactive protein, tumor
      necrosis factor-alpha, and Fas-Apo-1 were also studied in PPCMs. RESULTS: All
      PPCM groups were similar in Ig profiles. The immunoglobulins, frequencies and
      reactivities, were markedly and nonselectively raised in PPCM patients compared
      with DCM. Immunoglobulin frequencies in PPCMs, Haiti: G1 58%, G2 66%, G3 54%;
      Mozambique: G1 77%, G2 66%, G3 66%; and South Africa: G1 47%, G2 53%, G3 53%,
      were higher compared with DCMs from South Africa (n = 24): G1 8%, G2 8%, G3 21%,
      or the United Kingdom (n = 68): G1 10%, G2 8.8%, G3 22% (P < .0001). Hence,
      unlike the selective up-regulation of immunoglobulins of the G3 subclass (IgG3s)
      in DCM, class G and all subclass immunoglobulins were raised in PPCM. Of the
      serological variables, IgG3s (immunoglobulins with proinflammatory
      characteristics) discriminated NYHA functional status at diagnosis. IgG3-positive
      patients were in a higher NYHA class at initial presentation (P < .05).
      CONCLUSIONS: Immunoglobulin subclass profiles in patients with HF differ with
      etiology. Unlike DCM, the impact of pregnancy-related HF on humoral immunity is
      not subclass-restricted. However, raised levels of IgG3s may be of prognostic
      value in clinical PPCM.

PMID- 16086929
TI  - Walking may be related to less vascular stiffness in the Activity Counseling
      Trial (ACT).
AB  - BACKGROUND: The ACT was a clinical trial of various patient education and
      counseling interventions to increase physical activity in sedentary primary care
      populations. It provided the opportunity to measure the effect of increasing
      physical activity on aortic pulse wave velocity (APWV), a measure of vascular
      stiffness, in a relatively healthy middle-aged population. The effects of the
      interventions, as well as the impact of walking and correlates such as older age
      and maximal oxygen uptake (VO2max), on APWV were assessed. METHODS: The
      participants in this study were a subset of the 874 persons recruited for the
      ACT. Information about self-reported physical activity and disease status was
      collected at baseline (464 persons), 6-month (528 persons), and 24-month (555
      persons) intervals. Physiological measures included APWV, systolic blood
      pressure, and other correlates. RESULTS: In multivariate analyses, the various
      treatment arms did not have a significant effect on APWV. However, walking in
      hours per day was associated with slower APWV times or less stiffness (P = .03).
      This was significant for women and consistent but not significant for men. In
      addition, age, clinic site, race, systolic blood pressure, and VO2max were
      independently associated with APWV. CONCLUSIONS: Increased walking frequency over
      a 24-month period was predictive of reduced vascular stiffness in ACT. The more
      significant result for walking frequency in women than in men might be caused by
      the presence of a low Vo2max or physical activity threshold for an effect of
      walking on APWV, which most women achieved but most men had surpassed at the
      start of the study. Although needing confirmation because this was a secondary
      analysis, modest physical activity may have a beneficial effect on large vessel
      structure.

PMID- 16086930
TI  - Patterns of inflammation associated with peripheral arterial disease: the
      InCHIANTI study.
AB  - OBJECTIVE: To determine whether peripheral arterial disease is associated with
      high circulating levels of pro-inflammatory cytokines, independent of
      confounders. METHODS: Participants were 955 men and women aged 60 years and older
      representative of the population in 2 Italian communities (107 with peripheral
      arterial disease). Measurements included the ankle brachial index, comorbidities,
      total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels, and
      these inflammatory factors: albumin, alpha-2 macroglobulin, C-reactive protein,
      fibrinogen, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-6, IL-6
      receptor, IL-10, IL-18, tumor necrosis factor alpha, and transforming growth
      factor beta. RESULTS: Adjusting for age, sex, body mass index, smoking,
      comorbidities, HDL-C, and total cholesterol, participants with peripheral
      arterial disease had higher levels of IL-1 receptor antagonist (147.97 vs 131.24
      pg/mL, P = .002), IL-6 (1.65 vs 1.37 pg/mL, P = .026), fibrinogen (362.49 vs
      345.50 mg/dL, P = .039), and C-reactive protein (3.18 vs 2.56 mg/dL, P = .043)
      compared with those without peripheral arterial disease. These associations were
      attenuated after additional adjustment for physical activity. CONCLUSION: In a
      community population, peripheral arterial disease is associated with increased
      circulating levels of IL-6, IL-1 receptor antagonist, fibrinogen, and C-reactive
      protein compared to persons without peripheral arterial disease. Further study is
      needed to determine whether reducing levels of certain inflammatory factors
      lowers the incidence and progression of peripheral arterial disease.

PMID- 16086931
TI  - The benefit of cholesterol-lowering medications after coronary revascularization:
      a population study.
AB  - BACKGROUND: In clinical trials, cholesterol-lowering medications have been proven
      to decrease mortality and morbidity and are strongly recommended as secondary
      prevention in patients with established coronary artery disease. In routine
      practice, the translation of these benefits to elderly patients with recent
      coronary revascularization is less well known. METHODS: Using the provincial
      computerized administrative databases of the Regie de l'Assurance Maladie du
      Quebec, we identified all elderly patients (>65 years old) in Quebec, Canada,
      discharged alive after a coronary revascularization procedure (percutaneous
      coronary intervention or coronary artery bypass graft) between April 1, 1995, and
      December 31, 1997, and determined the percentage fulfilling prescriptions for
      cholesterol-lowering drug therapy. Time-dependent multivariable models examined
      the clinical end points of total mortality, acute myocardial infarctions, and
      repeat coronary revascularizations as a function of cholesterol-lowering drug
      exposure. Patients were followed up until death or December 31, 1999. RESULTS: We
      identified 11958 elderly patients who had a coronary revascularization between
      April 1, 1995, and December 31, 1997. During an average 3-year follow-up, users
      of cholesterol-lowering medications had a decreased risk of death [hazard ratio
      (HR) 0.66, 95% CI 0.45-0.96] or myocardial infarction (HR 0.77, 95% CI 0.54-1.11)
      but no reduction in repeat revascularizations (HR 1.06, 95% CI 0.88-1.28).
      CONCLUSIONS: In this population-based study of recently revascularized elderly
      patients, we observed health benefits associated with the use of cholesterol
      lowering medications of similar size to those seen in randomized clinical trials.
      The translation of these benefits from clinical trials to a nonselected
      population of revascularized patients emphasizes the importance of this aspect of
      secondary prevention in clinical practice.

PMID- 16086932
TI  - Plasma low-density lipoprotein reduction and structural effects on coronary
      atherosclerotic plaques by atorvastatin as clinically assessed with intravascular
      ultrasound radio-frequency signal analysis: a randomized prospective study.
AB  - BACKGROUND: Plaque stabilization by statins is important for reduction of
      cardiovascular events but has not been demonstrated enough in vivo. We examined
      whether statins clinically alter the structure of coronary atherosclerotic
      plaques using intravascular ultrasound (IVUS) radio-frequency (RF) signal
      analysis. METHODS: Fifty consecutive patients undergoing percutaneous coronary
      intervention were enrolled. Intravascular ultrasound radio-frequency signals were
      acquired from non-percutaneous coronary intervention-targeted echolucent plaques.
      The patients were randomly assigned into 2 groups: group S (n = 25) taking
      atorvastatin 10 mg/d and group C (n = 25) as control. After 6-month follow-up,
      IVUS-RF signals were sampled at the same plaque sites. Several regions of
      interest were placed on each plaque. Intravascular ultrasound radio-frequency
      parameters were blindly calculated in all regions of interests (group S, n = 148;
      group C, n = 191). Targeted plaque volumes were also measured. Those data were
      compared between baseline and follow-up. RESULTS: In group S after 6 months,
      plasma low-density lipoprotein level was significantly decreased (133 +/- 13 to
      87 +/- 29 mg/dL, P < .0001), integrated backscatter of IVUS-RF signals was
      substantially increased (-53.8 +/- 4.5 to -51.2 +/- 4.9 dB, P < .0001), and
      plaque volume was significantly reduced, whereas no change was demonstrated in
      group C. CONCLUSIONS: These results suggest that statins alter properties as well
      as volumes of coronary plaques within 6 months, which may be related to plasma
      low-density lipoprotein reduction. Intravascular ultrasound radio-frequency
      signal analysis may be useful to evaluate the effects of drugs on stabilization
      of coronary atherosclerotic plaques.

PMID- 16086933
TI  - Left Atrial Appendage Occlusion Study (LAAOS): results of a randomized controlled
      pilot study of left atrial appendage occlusion during coronary bypass surgery in
      patients at risk for stroke.
AB  - AIM: This pilot study assessed the safety and efficacy of left atrial appendage
      (LAA) occlusion, performed at the time of coronary artery bypass grafting (CABG).
      METHODS AND RESULTS: At the time of CABG, 77 patients with risk factors for
      stroke were randomized to LAA occlusion or control. The LAA was occluded using
      sutures or a stapling device. Completeness of occlusion was assessed with
      transesophageal echocardiography. There were no significant differences in
      cardiopulmonary bypass duration, perioperative heart failure, atrial
      fibrillation, or bleeding between the 2 groups. During surgery, there were 9
      appendage tears, all of which were repaired easily with sutures. Among patients
      having a postoperative transesophageal echocardiography, complete occlusion of
      the LAA was achieved in 45% (5/11) of cases using sutures and in 72% (24/33)
      using a stapler, P = .14. The rate of LAA occlusion by individual surgeons
      increased from 43% (9/21) to 87% (20/23) after performing 4 cases (P = .0001).
      After a mean follow-up of 13 +/- 7 months, 2.6% of patients had thromboembolic
      events. CONCLUSIONS: LAA occlusion at the time of CABG is safe. The rate of
      complete occlusion improves, to acceptable levels, with increased experience and
      the use of a stapling device. A large trial is needed to determine if LAA
      occlusion prevents stroke.

PMID- 16086934
TI  - Regional myocardial velocities and isovolumic contraction acceleration before and
      after device closure of atrial septal defects: a color tissue Doppler study.
AB  - BACKGROUND: The study analyzed the effect of atrial septal defect (ASD) device
      closure on regional wall motion in the right (RV) and left ventricles (LV) using
      color tissue Doppler imaging (TDI). Atrial septal defect closure results in acute
      volume unloading of the RV. For unknown reasons, some patients develop acute left
      sided heart failure postintervention. METHODS: Color TDI was performed in 39
      pediatric ASD and 75 age-matched controls. Regional wall motion in 5 LV and 1 RV
      segment were analyzed before, immediately after, and 24 hours after
      interventional ASD closure. Off-line postprocessing of echocardiographic data was
      used to determine myocardial velocities and acceleration during isovolumic
      contraction (IVA). Isovolumic contraction acceleration is the slope of the
      upstroke of the isovolumic contraction wave (IVA = peak velocity/acceleration
      time). RESULTS: At baseline, patients with ASD had significantly higher RV
      systolic velocities than controls. Isovolumic contraction acceleration was
      similar in patients with ASD and controls. In the catheterization laboratory
      postintervention, conventional function parameters remained stable but systolic
      myocardial velocities decreased significantly in all segments. Diastolic
      velocities fell in LV segments but not in the RV. In contrast to velocities, IVA
      was stable during ASD device closure. On follow-up at 24 hours, myocardial
      velocities had normalized. CONCLUSIONS: Device closure of ASD results to an acute
      transient decrease of regional myocardial velocities in the LV and RV, whereas
      the load-insensitive marker isovolumic acceleration remained stable. Therefore,
      the velocity changes may represent a response to altered left and right
      ventricular loading conditions. Color TDI is a sensitive tool to analyze
      ventricular mechanics.

PMID- 16086935
TI  - Impact of vitamin E and C supplementation on serum adhesion molecules in chronic
      degenerative aortic stenosis: a randomized controlled trial.
AB  - BACKGROUND: An inflammatory component has been identified in degenerative aortic
      stenosis (AS). The combination of vitamins E and C has been shown to have anti
      inflammatory properties. The aim of this study was to determine the impact of the
      combination of vitamins C and E or vitamin C only on serum levels of cell
      adhesion molecules and C-reactive protein in patients with chronic degenerative
      AS, with or without concomitant coronary artery disease. METHODS AND RESULTS: One
      hundred patients with asymptomatic or mildly symptomatic moderate AS were
      randomized in 2:2:1 format in an open-label trial. Forty-one patients received
      vitamin E (400 IU) and vitamin C (1000 mg) daily, 39 patients received vitamin C
      (1000 mg) only, and 20 patients were followed as controls. Serum intracellular
      adhesion molecule (ICAM-1), E selectin, P selectin, vascular-cellular adhesion
      molecule (VCAM-1), C-reactive protein, and alpha-tocopherol (vitamin E) were
      measured by enzyme-linked immunosorbent assay at baseline and 6 months
      postsupplementation. Half of the patients from each of the 2 active groups were
      followed for further 6 months to determine any changes after cessation of
      therapy. In the vitamin E and C, group there was reduction in serum ICAM-1 (298
      +/- 12 to 272 +/- 12 ng/mL at 6 months, P = .0015) with a return to base line 6
      months after cessation of therapy. In the vitamin C only group, there was a
      reduction in serum P selectin (134 +/- 10 to 118 +/- 10 ng/mL at 6 months, P =
      .033). All the inflammatory markers were unchanged in control group over 6 months
      of follow-up. CONCLUSION: Vitamin E and C supplementation had modest anti
      inflammatory effect in chronic degenerative AS. The clinical relevance of this
      would require further clarification.

PMID- 16086936
TI  - Can we reliably predict long-term mortality after exercise testing? An external
      validation.
AB  - OBJECTIVE: The aim of the study was to derive and externally validate a mortality
      prediction rule for patients undergoing exercise testing. BACKGROUND: The
      prognostic value of exercise testing is increasingly appreciated. However, global
      prognosis estimates ideally should account for numerous routinely obtained
      variables, including demographics, risk factors, resting electrocardiogram, and
      multiple exercise test measures. METHODS: A prediction rule was derived by
      parametric hazards modeling on a derivation set of 46047 Cleveland Clinic
      patients (age 55 +/- 11 years, 67% male) who had no history of heart failure,
      valve disease, or atrial fibrillation. Twenty-two variables covering
      demographics, risk factors, exercise hemodynamics, and electrocardiogram findings
      at rest and during exercise were considered. The resulting model included 16
      variables and was tested on 4981 patients (age 50 +/- 12 years, 55% male) who
      underwent exercise testing at West Virginia University. RESULTS: In the
      derivation cohort there were 3173 deaths during a mean of 7 years of follow-up,
      whereas in the validation cohort there were 180 deaths during a mean of 5 years
      of follow-up. Comparisons of predicted and observed death rates showed very good
      agreement among all patients across all spectrums of risk, as well as among
      prespecified high-risk subgroups. Model discrimination was also good, with c
      statistic of c = 0.79 in the derivation group and c = 0.81 in the validation
      cohort. CONCLUSIONS: We have externally validated a mortality prediction rule for
      patients undergoing exercise testing and confirmed its accuracy among a wide
      spectrum of patients.

PMID- 16086937
TI  - Coronary venous imaging with electron beam computed tomographic angiography:
      three-dimensional mapping and relationship with coronary arteries.
AB  - BACKGROUND: The coronary venous system can provide vascular access for diagnostic
      and therapeutic procedures. Visualization of the coronary veins and their
      relationship to other cardiac structures may play an important role in
      facilitating these procedures. We sought to assess the ability of electron beam
      computed tomographic angiography (EBCTA) to characterize 3-dimensional (3-D)
      coronary venous anatomy. METHODS: Two hundred thirty-one consecutive EBCTA
      coronary studies were analyzed. The coronary venous system was mapped and
      analyzed using 2- and 3-D images with definition of diameter and angulations of
      branch vessels and distance from CS os. RESULTS: The coronary sinus (CS), great
      cardiac, middle cardiac, left ventricular (LV) anterior interventricular, LV
      marginal, LV posterior, left atrial, and right atrial veins were visualized in
      100%, 100%, 100%, 100%, 78%, 81%, 6%, and 8% of the studies, respectively, with
      definition of diameter and angulations of branch vessels and distance from CS os.
      There was a significant linear correlation between CS diameter and right atrial
      end systolic volume (R = 0.244, n = 81, P < .05). No significant correlation
      existed between CS os diameter and other cardiac size or function parameters. The
      3-D spatial arrangements between the coronary veins and the coronary arteries in
      relation to the epicardium were able to be defined, on the basis of the vessel
      closer to the epicardium in overlapping segments. CONCLUSIONS: EBCTA can provide
      3-D visualization of most components of the coronary venous system and definition
      of the spatial relationships with coronary arteries. EBCTA may potentially serve
      as a useful noninvasive tool for coronary venous imaging for procedures involving
      coronary veins, such as resynchronization therapy.

PMID- 16086938
TI  - Resource use, costs, and quality of life among patients in the multinational
      Valsartan in Acute Myocardial Infarction Trial (VALIANT).
AB  - BACKGROUND: In a multinational clinical trial, valsartan was statistically not
      inferior to captopril in reducing mortality and cardiovascular morbidity after
      myocardial infarction (MI) in patients with signs of heart failure and/or left
      ventricular dysfunction. We conducted a prospective economic evaluation to
      compare within-trial resource use, costs, and quality of life in patients
      receiving valsartan, captopril, or both after MI. METHODS: We assigned country
      specific unit costs to resource use data for 14703 patients and measured health
      related quality of life in a subset of 4524 patients. We used the nonparametric
      bootstrap method to compare rates of resource use and costs, and a piecewise
      linear mixed-effects regression analysis to compare longitudinal measures of
      quality of life. RESULTS: There were no significant differences in rates of
      resource use between the valsartan and captopril groups. During an average follow
      up of 2 years, total costs for patients receiving valsartan were significantly
      higher than for patients receiving captopril (USD 14103 vs USD 13038; 95% CI USD
      369-USD 1875). The cost differential was caused primarily by the cost of the
      study medications (USD 1056 for valsartan vs USD 165 for captopril; 95% CI USD
      867 to USD 912). Quality of life did not differ significantly between groups.
      CONCLUSIONS: For most patients at high risk after MI, the availability of generic
      captopril confers a cost advantage over valsartan because of lower medication
      costs. The difference will be smaller or nonexistent in settings where brand-name
      ACE inhibitors are prescribed.

PMID- 16086939
TI  - Inhospital and 1-year mortality of patients who develop worsening renal function
      following acute ST-elevation myocardial infarction.
AB  - BACKGROUND: Recent studies have emphasized the prognostic value of baseline
      creatinine or estimated creatinine clearance in the setting of acute coronary
      syndromes. However, the prevalence and prognostic significance of worsening renal
      function (WRF) in patients with acute ST-elevation myocardial infarction are
      unknown. METHODS: We studied 1038 patients presenting with acute ST-elevation
      infarction. WRF was defined as an increase of > or =0.5 mg/dL in creatinine level
      at any point during hospital stay. The relation between WRF and subsequent
      inhospital and 1-year mortality was analyzed by use of multivariate logistic
      regression and Cox proportional hazards models, respectively, controlling for
      covariates. RESULTS: WRF occurred in 98 (9.6%) patients during hospital stay.
      Baseline renal dysfunction (calculated glomerular filtration rate <60 mL/min) and
      WRF were strong independent predictors of inhospital mortality (adjusted odds
      ratios 2.8, 95% CI 1.3-5.9; and 11.4, 95% CI 6.6-19.5, respectively). In a Cox
      multivariate analysis, both baseline renal dysfunction (adjusted hazard ratio
      2.8, 95% CI 1.6-4.9) and WRF (adjusted hazard ratio 7.2, 95% CI 4.9-10.4)
      remained independent predictors of 1-year mortality. WRF provided incremental
      prognostic value toward the prediction of 1-year mortality when added to clinical
      risk predictors and baseline renal function. The increased mortality associated
      with impaired baseline renal function was largely caused by events occurring in
      patients with WRF. CONCLUSION: WRF occurring during admission for ST-elevation
      myocardial infarction is a powerful and independent predictor of inhospital and 1
      year mortality. Small elevations of serum creatinine may serve as a simple marker
      to identify patients at a very high risk.

PMID- 16086940
TI  - Effect of lesion length on fractional flow reserve in intermediate coronary
      lesions.
AB  - BACKGROUND: Fractional flow reserve (FFR) has become a gold standard in
      physiological assessment of coronary artery stenosis. An FFR < 0.75 is considered
      as a reliable physiological parameter indicating functionally significant lesion.
      Lesion length (LL) may affect the translesional hemodynamics. However, the effect
      of LL on FFR has not been adequately assessed. We sought to evaluate the effect
      of LL on FFR in patients with angiographically intermediate coronary artery
      disease. METHODS: We performed FFR measurements by pressure guidewire in 63
      intermediate-grade lesions (63 patients) by visual assessment. Lesion length and
      percent diameter stenosis (%DS) at the lesion site were determined by performing
      off-line quantitative coronary angiography analysis. RESULTS: Overall, there was
      a moderate inverse correlation between FFR and %DS (r = -0.55, P < .001). In
      addition, there was a weak inverse correlation between LL and FFR (r = -0.31, P <
      .001). Using a receiver operating characteristic curve analysis, an LL > or = 10
      mm was identified as the best cutoff value for predicting an FFR < 0.75
      (sensitivity 95%, specificity 66%, positive predictive power 48%, and negative
      predictive power 97%). The correlation between FFR and %DS was significantly
      improved for LL > or = 10 mm, as compared with LL < 10 mm (r = -0.78, P < .001; r
      = 0.16, P = NS; respectively). Similar improvement with LL was also observed for
      intermediate lesions by quantitative coronary angiography (%DS 50%-70%; r = 0.19,
      P = NS for LL < 10 mm; r = -0.74, P < .001 for LL > or = 10 mm). CONCLUSIONS:
      This study demonstrates that LL differentially affects the correlation between
      the functional assessment (FFR) and the "anatomic" severity (%DS) of coronary
      lesions and suggests that LL has a significant impact on the physiological
      significance of intermediate-grade coronary lesions.

PMID- 16086941
TI  - Inflammatory response after intervention assessed by serial C-reactive protein
      measurements correlates with restenosis in patients treated with coronary
      stenting.
AB  - OBJECTIVES: We hypothesized that a higher degree of inflammatory response to
      coronary stenting, as measured by the change in C-reactive protein (CRP) levels
      after intervention in patients with stable or unstable angina, would be related
      to a higher risk of in-stent restenosis. METHODS: We studied 1800 consecutive
      patients with stable or unstable angina treated with coronary stenting. C
      reactive protein levels were serially measured before and after the intervention.
      The difference (Delta) between highest CRP values after intervention and CRP
      values before intervention was calculated. Patients were grouped into tertiles
      according to DeltaCRP values. The primary end point was angiographic restenosis
      (diameter stenosis > or = 50% at 6-month angiography). The secondary end point
      was clinical restenosis, defined as target vessel revascularization performed in
      the presence of angiographic restenosis and symptoms or signs of ischemia.
      RESULTS: No relationship was found between CRP values at baseline and
      angiographic restenosis (P = .88). On the other hand, the change between baseline
      and peak postintervention CRP values strongly correlated with angiographic
      restenosis (30.5% in the upper tertile with DeltaCRP values >11.8 mg/L, 25.3% in
      the middle tertile with DeltaCRP values 3.0-11.8 mg/L, and 21.5% in the lower
      tertile with DeltaCRP values < 3.0 mg/L, P = .002) as well as with clinical
      restenosis (P = .01). Patients in the upper tertile had the highest risk of
      restenosis even after adjustment for other covariates. CONCLUSIONS: The
      inflammatory response to coronary stenting as assessed by the change in CRP
      correlates with the development of in-stent restenosis. These findings provide
      strong support for the role of inflammation in restenosis.

PMID- 16086942
TI  - Sirolimus-eluting stent implantation and beta-irradiation for the treatment of in
      stent restenotic lesions: comparison of underlying mechanisms of acute gain and
      late loss as assessed by volumetric intravascular ultrasound.
AB  - BACKGROUND: The aim of the study was to compare the angioplasty mechanisms of
      drug (sirolimus)-eluting stent (DES) implantation and vascular brachytherapy
      (VBT) for the treatment of in-stent restenosis (ISR) as assessed by intravascular
      ultrasound (IVUS). METHODS: We performed IVUS in 53 patients (28 DES, 25 VBT)
      before and after angioplasty of ISR and at 6-month follow-up. Cross-sectional
      areas of the external elastic membrane, the stent, and the lumen were measured.
      Plaque + media, peristent plaque, and intimal hyperplasia areas were calculated,
      respectively. RESULTS: Clinical and IVUS baseline characteristics did not differ
      between groups at baseline. After the index procedure, the lumen at the stent
      site was smaller in the DES group (DES 6.7 +/- 2.0 mm2 vs VBT 7.5 +/- 2.2 mm2, P
      = .042). Because of less intimal hyperplasia (DES 0.2 +/- 0.5 mm2 vs VBT 0.7 +/-
      0.7 mm2, P = .043), the lumen dimensions revealed no difference between groups at
      follow-up (DES 6.5 +/- 2.3 mm2 vs VBT 6.8 +/- 2.2 mm2, P = .374). At the
      reference site, the index procedure led to a similar increase of plaque + media
      (DES 0.9 +/- 0.9 mm2 vs VBT 0.6 +/- 1.2 mm2, P = .150). At follow-up, the plaque
      + media was significantly smaller in the DES group (DES 8.0 +/- 6.6 mm2 vs VBT
      9.9 +/- 7.8 mm2, P = .013). CONCLUSIONS: Drug-eluting stent for the treatment of
      ISR more effectively inhibits neointima formation when compared with VBT. Yet
      insufficient stent expansion might be a reason for device failure and should be
      avoided. At the reference site, lumen loss by an increased plaque burden, as has
      been well recognized following VBT, is not present with DES.

PMID- 16086944
TI  - Tractional cystoid macular edema: a subtle variant of the vitreomacular traction
      syndrome.
AB  - PURPOSE: To describe clinical characteristics and treatment outcomes in a series
      of patients with tractional cystoid macular edema, a subtle variant of the
      vitreomacular traction syndrome. DESIGN: Retrospective, uncontrolled,
      observational, and interventional case series. METHODS:  PATIENT POPULATION: Ten
      consecutive patients (11 eyes) with multicystoid foveolar thickening caused by
      localized perifoveal vitreous detachment. EXPERIMENTAL PROCEDURES: Slit-lamp
      biomicroscopy and fluorescein angiography; confirmation of vitreomacular
      relationship with B-scan ultrasonography, optical coherence tomography (OCT), or
      both. Vitrectomy with peeling of posterior hyaloid in 8 eyes with pretreatment
      visual acuity <or=20/60. MAIN OUTCOME MEASURES: Visual acuity and resolution of
      cystoid macular edema at final follow-up. RESULTS: The median age of symptom
      onset was 71 years (range 48-81 years). Shallow perifoveal vitreous detachment
      was detectable on biomicroscopy in 8 of 11 eyes (73%) and with ultrasound and OCT
      in all eyes. Fluorescein angiography revealed no leakage from perifoveal
      capillaries in 8 eyes (73%). After a mean postoperative follow-up of 26.0 months
      (range 3-84 months), the final visual acuity had improved by 2 or more Snellen
      lines and measured 20/40 or better in 8 (100%) of 8 operated eyes. Cystoid foveal
      thickening resolved in all operated eyes. CONCLUSION: Subtle, localized
      perifoveal vitreous detachment may cause anterior traction on the foveola,
      resulting in multicystoid foveal thickening without macular hole formation or
      capillary leakage. OCT and ultrasound imaging are useful in detecting the
      detached posterior hyaloid when clinically invisible. Foveal thickening resolves
      and visual acuity typically improves after the relief of vitreofoveolar traction.

PMID- 16086943
TI  - Impact of smoking status on outcomes of primary coronary intervention for acute
      myocardial infarction--the smoker's paradox revisited.
AB  - OBJECTIVES: We sought to determine the relationship between cigarette smoking and
      outcomes after mechanical reperfusion therapy in acute myocardial infarction
      (AMI). BACKGROUND: Prior studies have found that smokers with AMI have lower
      mortality rates and a more favorable response to fibrinolytic therapy than
      nonsmokers. The impact of cigarette smoking in patients undergoing primary
      percutaneous coronary intervention has not been examined. METHODS: In the
      CADILLAC trial, 2082 patients with AMI were randomized to percutaneous
      transluminal coronary angioplasty +/- abciximab versus stenting +/- abciximab.
      Data on smoking status were prospectively collected and follow-up continued for 1
      year. RESULTS: At the time of presentation, 638 (31%) patients had never smoked,
      546 (26%) were former smokers, and 898 (45%) were currently smoking. In
      comparison to nonsmokers, current smokers were younger, more often men, and less
      frequently had diabetes, hypertension, prior AMI, and triple-vessel coronary
      disease. Procedural success rates were unrelated to smoking status. Mortality was
      lowest in current smokers, intermediate in former smokers, and highest in
      nonsmokers at 30 days (1.3% vs 1.7% vs 3.5%, respectively, P = .02) and 1 year
      (2.9% vs 3.7% vs 6.6%, P = .0008). After multivariate correction for differences
      in baseline variables, however, current smoking status was no longer protective
      from late mortality (hazard ratio 0.96, 95% CI 0.52-1.76, P = .89). CONCLUSIONS:
      The "smoker's paradox" extends to patients undergoing primary PCI for AMI, with
      increased survival seen in current smokers, an effect entirely explained by
      differences in baseline risk and not smoking status per se. The deleterious
      effects of smoking are expressed in the occurrence of AMI nearly a decade earlier
      than in nonsmokers, with similar age-adjusted risk, mandating intensive primary
      and secondary cigarette-cessation efforts.

PMID- 16086945
TI  - Involution of retinopathy of prematurity after laser treatment: factors
      associated with development of retinal detachment.
AB  - PURPOSE: To identify specific features during the process of involution of
      retinopathy of prematurity after treatment at threshold that are associated with
      development of a retinal detachment. DESIGN: Retrospective case series. METHODS:
      The evolution of retinal detachments over time was analyzed retrospectively in
      262 treated eyes of 138 infants. Specific features hypothesized to be associated
      with development of a retinal detachment were analyzed, including vitreous
      organization defined as clinically important, active stage 3 disease and active
      plus disease more than 21 days after treatment, and vitreous hemorrhage defined
      as clinically important. RESULTS: A retinal detachment developed in 36 (13.7%) of
      262 eyes. Vitreous organization meeting our clinically important definition was
      associated with a 31-fold (confidence interval [CI] 5.37-183.63; P < .0001) and
      13-fold (CI 2.97-58.59; P < .0001) increase in the odds for retinal detachment
      for right and left eyes, respectively. Vitreous hemorrhage defined as clinically
      important was associated with a 38-fold (CI 2.69-551.19; P = .007) and 15-fold
      (CI 1.65-144.12; P = .02) increase in the odds for retinal detachment for right
      and left eyes, respectively. The timing of retinal detachment relative to
      vitreous hemorrhage was not determined. Prolonged activity of Stage 3 disease or
      plus disease more than 21 days after treatment was not associated with
      development of a retinal detachment. CONCLUSIONS: Clinically important vitreous
      organization and vitreous hemorrhage were predictive for development of a retinal
      detachment. Evaluation of preemptive reintervention strategies for eyes at
      highest risk for developing a retinal detachment may be reasonable.

PMID- 16086946
TI  - Efficacy and safety of a fixed combination of travoprost 0.004%/timolol 0.5%
      ophthalmic solution once daily for open-angle glaucoma or ocular hypertension.
AB  - PURPOSE: To compare the efficacy of a fixed combination of travoprost
      0.004%/timolol 0.5% every day in the morning with a concomitant regimen of
      timolol 0.5% every day in the morning, plus travoprost 0.004% every day in the
      evening; and timolol 0.5% twice daily on the intraocular pressure (IOP) of
      subjects with open-angle glaucoma or ocular hypertension over 3 months. DESIGN:
      Prospective, randomized, double-masked, parallel-group, active-controlled,
      multicenter trial. METHODS: Patients comprised adult subjects (n = 403) of either
      gender with open-angle glaucoma or ocular hypertension in at least one eye. To
      qualify, the IOP had to be between 22 to 36 mm Hg in the same eye at two
      consecutive eligibility visits. The primary outcome variable was IOP measured
      with a Goldmann applanation tonometer. RESULTS: Mean IOP ranged from 16.2 to 17.4
      mm Hg with the combination travoprost/timolol compared with 15.4 to 16.8 mm Hg in
      the concomitant travoprost + timolol group, from baselines of 23.1 to 25.6 mm Hg
      and 22.9 to 25.0 mm Hg, respectively. The fixed combination of travoprost/timolol
      significantly lowered IOP by 7 to 9 mm, similar to the IOP reductions observed
      with concomitant therapy. The most frequent ocular adverse event was hyperemia
      that occurred in 14.3% and 23.4% of subjects treated with travoprost/timolol
      combination and concomitant travoprost + timolol, respectively. CONCLUSIONS:
      Travoprost/timolol combination produces greater IOP reductions than the positive
      control, timolol 0.5%, and reductions that were similar to concomitant travoprost
      + timolol. This study demonstrates that the fixed combination of
      travoprost/timolol produces significant and clinically relevant reductions of IOP
      in a once-daily dosing regimen.

PMID- 16086947
TI  - Pathogenesis of macular edema with branch retinal vein occlusion and intraocular
      levels of vascular endothelial growth factor and interleukin-6.
AB  - PURPOSE: To determine whether correlations between vascular endothelial growth
      factor (VEGF) or interleukin-6 (IL-6) contribute to the pathogenesis of macular
      edema in eyes of patients with branch retinal vein occlusion (BRVO). DESIGN:
      Retrospective case-control study. METHODS: Nineteen patients with macular edema
      with BRVO and seven patients with non-ischemic ocular disease (control group)
      were studied. The degree of retinal ischemia was evaluated in terms of the area
      of capillary non-perfusion, and the severity of macular edema was examined by
      optical coherence tomography. Aqueous humor samples were obtained at the time of
      combined vitrectomy and cataract surgery, and VEGF and IL-6 levels in aqueous
      humor and plasma were determined by enzyme-linked immunosorbent assay. RESULTS:
      Aqueous levels of VEGF (351 +/- 273 pg/ml) and IL-6 (7.10 +/- 6.51 pg/ml) were
      significantly elevated in patients with BRVO compared with the control patients
      (119 +/- 38.7 pg/ml and 2.27 +/- 1.11 pg/ml, respectively) (P = .0017 and P =
      .0052, respectively). Aqueous level of VEGF was significantly correlated with
      that of IL-6 (P = .0396), and aqueous levels of VEGF and IL-6 were correlated
      with the size of the BRVO non-perfused area (P < .0001 and P = .0331,
      respectively). Aqueous level of VEGF was correlated with the severity of macular
      edema (P = .0306). CONCLUSIONS: VEGF and IL-6 may be involved in the pathogenesis
      of macular edema with BRVO. The increase in these cytokines might be used as a
      unique index of BRVO, through which we can determine the severity of the ischemic
      condition as being in a quiescent state or an exacerbation of macular edema.

PMID- 16086948
TI  - Splendore-Hoeppli phenomenon in the conjunctiva: immunohistochemical analysis.
AB  - PURPOSE: To present two cases of conjunctival lesions exhibiting the Splendore
      Hoeppli phenomenon, each with different immunohistochemical findings. DESIGN:
      Interventional case reports. METHODS: Two young males with conjunctival lesions
      underwent biopsy. Demographic data and timing of biopsy were extracted from the
      charts. The biopsy specimens were formalin fixed and paraffin embedded for light
      microscopy. Immunohistochemical staining using the peroxidase method was carried
      out on each for IgG, IgM, IgA, the C3 component of complement, and eosinophilic
      major basic protein. MAIN OUTCOME MEASURES: Presence of positive or negative
      staining for the various antigens. RESULTS: Both biopsy specimens exhibited the
      Splendore-Hoeppli phenomenon, a morphologically unique process consisting of an
      amorphous, eosinophilic material surrounded by epithelioid histiocytes,
      multinucleated giant cells, lymphocytes, and eosinophils. Two staining patterns
      were seen. One revealed predominately immunoglobulin deposition, whereas the
      other revealed primarily eosinophilic major basic protein. This is the first
      instance we are aware of in which eosinophilic major basic protein was the
      predominate finding in an ocular specimen. CONCLUSION: The composition of
      Splendore-Hoeppli phenomenon material varies and may be related to various
      factors, including timing of biopsy and prior treatment.

PMID- 16086949
TI  - The tube versus trabeculectomy study: design and baseline characteristics of
      study patients.
AB  - PURPOSE: The Tube Versus Trabeculectomy (TVT) Study will compare the safety and
      efficacy of nonvalved tube shunt surgery to trabeculectomy with mitomycin C in
      patients with previous intraocular surgery. DESIGN: Multicenter randomized
      clinical trial. METHODS:  SETTING: 17 Clinical Centers. STUDY POPULATION:
      Patients 18 to 85 years of age who have undergone previous trabeculectomy,
      cataract extraction with intraocular lens implantation, or both and have
      inadequately controlled glaucoma with intraocular pressure (IOP) >or=18 mm Hg and
      <or=40 mm Hg on tolerated medical therapy. INTERVENTIONS: Study patients were
      randomized to undergo placement of a 350-mm(2) Baerveldt glaucoma implant or
      trabeculectomy with mitomycin C (0.4 mg/ml for 4 minutes). MAIN OUTCOME MEASURES:
      IOP, complication rates, visual acuity, visual field, quality of life,
      reoperations for glaucoma, and need for supplemental medical therapy. RESULTS: A
      total of 212 patients were enrolled between October 1999 and April 2004. The age
      of the study population was 71.0 +/- 10.4 years (mean +/- SD), and 53% were
      women. The baseline IOP was 25.3 +/- 5.3 mm Hg (mean +/- SD). There were no
      significant differences in the demographic and ocular characteristics between the
      2 treatment groups. CONCLUSIONS: Practice patterns vary in the surgical
      management of glaucoma, and there are differing opinions among glaucoma surgeons
      regarding the preferred surgical approach in patients who have undergone previous
      cataract extraction and/or failed filtering surgery. Forthcoming data from the
      TVT Study should provide valuable information comparing two surgical procedures
      commonly used in this patient population.

PMID- 16086950
TI  - The science and marketing of dietary supplements.

PMID- 16086951
TI  - Survival analysis of conjunctival limbal grafts and amniotic membrane
      transplantation in eyes with total limbal stem cell deficiency.

PMID- 16086952
TI  - Non-invasive measurement of intraocular pressure by near-infrared spectroscopy.
AB  - PURPOSE: To assess a new non-contact method for non-invasive measurement of
      intraocular pressure (IOP) using near-infrared spectroscopy. DESIGN: Experimental
      study. METHODS: Eleven porcine eyes were cannulated into the anterior chamber by
      a needle connected with a water column. Measuring the near-infrared spectrum in
      diffuse reflectance out of the anterior chamber by near-infrared spectroscopy,
      IOP was determined and compared with the height of the water column which was
      varied between 0 cm and 100 cm. RESULTS: In total, 363 near-infrared
      spectrometric measurement values were obtained. Correlating the near-infrared
      spectrometric measurements with the height of the water column showed a
      relationship with a correlation coefficient of r(2) = .858 and a steepness of the
      regression line of .96. CONCLUSIONS: The results of the present pilot study
      suggest that near-infrared spectrometric tonometry may present a new technology
      for non-invasive and non-contact IOP measurement.

PMID- 16086953
TI  - Diamond burr treatment of poor vision from anterior basement membrane dystrophy.
AB  - PURPOSE: To determine the outcome of patients with decreased vision associated
      with anterior basement membrane dystrophy (ABMD) managed with diamond burr (DB)
      polishing. DESIGN: Retrospective nonrandomized case series. METHODS: A chart
      review of all patients with ABMD who underwent epithelial debridement and DB
      polishing to treat visual disturbances resulting from corneal epithelial
      irregularity was performed. RESULTS: Ten patients' charts were analyzed. The mean
      age was 57.4 years. DB treatment was performed in 13 eyes. The average
      preoperative BCVA was 0.40 (20/50). At the last follow-up (mean 21.8 months) the
      average visual acuity of these patients was 0.88 (20/23), significantly better
      than pre-operative readings (P < .001). There was no recurrence of dystrophic
      changes in the treatment zone seen with the slit lamp during the follow-up
      period. CONCLUSIONS: In this study, DB polishing was shown to be an effective and
      safe treatment for decreased vision caused by to ABMD over an average follow-up
      of 21.8 months.

PMID- 16086955
TI  - Photodynamic therapy for choroidal neovascularization on late-onset fundus
      flavimaculatus.
AB  - PURPOSE: To report the features of three consecutive cases of patients affected
      with late-onset fundus flavimaculatus (FFM) complicated with choroidal new
      vessels (CNV) and treated with photodynamic therapy (PDT). DESIGN: Retrospective
      interventional case series. METHODS: Three unrelated women (70- to 74-year-old)
      presented with unilateral decrease of central vision. Diagnosis of FFM and
      unilateral CNV was made after fundus examination and fluorescein angiography
      (FA). PDT was performed on the basis of FA features. RESULTS: One to three PDTs
      were needed for the treatment of CNV. At the end of follow-up (15-24 months), no
      leakage was present and visual acuity was improved in these three cases.
      CONCLUSIONS: Occurrence of CNV is a rare event in FFM. In these three eyes, PDT
      successfully stopped the progression of CNV and blocked leakage. We suggest
      considering PDT as a treatment for CNV in patients affected with FFM.

PMID- 16086954
TI  - Simultaneous choroidal tuberculoma and epididymo-orchitis caused by Mycobacterium
      tuberculosis.
AB  - PURPOSE: To report positive polymerase chain reaction (PCR) for Mycobacterium
      tuberculosis from the vitreous and epididymal fluid in a patient of choroidal
      tuberculoma and epididymitis. DESIGN: Interventional case report. METHODS: 
      SETTING: Institutional setting. intervention: Vitreous and epididymal fluid tap
      subjected to PCR for primer IS 6110 sequence specific for M. tuberculosis.
      Purification of DNA product and sequencing on an automated DNA sequencer.
      Institution of antitubercular therapy. MAIN OUTCOME MEASURE: Matching of sequence
      with NCBI's data bank response to antitubercular therapy. RESULTS: DNA products
      from vitreous and epidiymal fluid matched with IS 6110 sequence of M.
      tuberculosis. Choroidal granuloma and epididymitis responded to antitubercular
      therapy. CONCLUSIONS: Simultaneous choroidal tuberculoma and epididymitis
      resulted from an infection by M. tuberculosis, and both matched with IS 6110
      sequence of M. tuberculosis.

PMID- 16086956
TI  - The value of visual evoked potentials in the evaluation of periorbital
      hemangiomas.
AB  - PURPOSE: To present a case of a child with an extensive facial hemangioma in whom
      the suspicion of intracranial involvement was raised by visual evoked potential
      (VEP) evaluation. DESIGN: Observational case report. METHODS: VEP analysis was
      performed using flash and pattern stimuli to determine whether treatment
      intervention other than occlusion therapy was needed. RESULTS: VEP analysis
      indicated a marked transoccipital asymmetry in the flash and pattern VEP
      suggestive of right hemispheric dysfunction. Neuroimaging showed intracranial
      extension of the hemangioma. CONCLUSION: The VEP evaluation is a noninvasive
      technique performed in the awake child. This case highlights the usefulness of
      VEP analysis in the management of extensive periocular capillary hemangiomas and
      its use as a modality to identify potential intracranial involvement. Large
      plaquelike facial capillary hemangiomas may have possible underlying dural
      involvement suggestive of PHACES syndrome.

PMID- 16086957
TI  - Spontaneous rip of the retinal pigment epithelium with a macular hole in
      neovascular age-related macular degeneration.
AB  - PURPOSE: To report a case of retinal pigment epithelial tear associated with a
      macular hole in a patient with neovascular age-related macular degeneration
      (AMD). DESIGN: Observational case report. METHODS: An 87-year-old woman with AMD
      related fibrovascular pigment epithelial detachment associated with vision loss
      was followed with sequential fundus photography, fluorescein angiography, and
      optical coherence tomography for 8 months. RESULTS: The detachment developed into
      a retinal pigment epithelium tear with macular hole formation. The temporal
      evolution of the lesion and optical coherence tomography findings suggested that
      the retinal pigment epithelium tear led to stretching forces along the posterior
      surface of the neurosensory retina with secondary foveal dehiscence. CONCLUSION:
      Macular hole formation is one mechanism by which retinal pigment epithelium tears
      may cause vision loss in AMD.

PMID- 16086958
TI  - Dynamic contour tonometry for intraocular pressure measurement.
AB  - PURPOSE: To compare dynamic contour tonometry as a new method for intraocular
      pressure measurement with Goldmann applanation tonometry. DESIGN: Clinical
      observational study. METHODS: The study included 176 eyes of 126 subjects (39
      eyes with open-angle glaucoma, 137 normal eyes) and consisted of 528 dynamic
      contour measurements and 352 Goldmann tonometry measurements. Corneal pachymetry
      measurements were additionally performed. RESULTS: Mean dynamic contour
      tonometric measurements (18.71 +/- 5.90 mm Hg) were significantly (P < .001)
      higher than mean applanation tonometric values (16.98 +/- 5.86 mm Hg),
      correlating significantly with each other (r(2) = .905, P < .001). The slope of
      the regression line was 0.95. Correlation with central corneal thickness was
      significant for applanation tonometry (P = .036), while dynamic contour tonometry
      was statistically independent of corneal thickness (P = .32). CONCLUSIONS: For
      measurement of intraocular pressure, dynamic contour tonometry may offer a new
      technology, which, compared with applanation tonometry, may show a lower
      dependence on central corneal thickness.

PMID- 16086959
TI  - Selective staining of the internal limiting membrane using the sequential
      intraoperative instillation of whole blood followed by indocyanine green dye.
AB  - PURPOSE: To reduce the retention of indocyanine green (ICG) on the retina by
      selectively staining the internal limiting membrane (ILM) with whole blood during
      ICG-assisted ILM peeling. DESIGN: Interventional, non-comparative, prospective
      case series. METHODS: Autologous whole blood was applied to cover the macular
      area and selectively removed to expose the area needed to be stained. ICG
      solution (1 mg/ml) diluted in glucose 5% was used to selectively stain the
      macular area. The stained ILM was removed completely. RESULTS: We studied 22
      patients with macular holes, eight with macular pucker and four with diabetic
      macular edemas. The ILM was selectively stained successfully by ICG with whole
      blood. One month after surgery, we found no autofluorescence in the posterior
      pole by infrared-sensitive camera. CONCLUSIONS: Autologous whole blood can help
      to achieve the goal of selectively staining ILM, further reducing the retention
      of ICG. It may further reduce ICG toxic effects.

PMID- 16086960
TI  - Corneal toxicity and inflammation secondary to retained perfluorodecalin.
AB  - PURPOSE: To describe a case with bullous keratopathy and anterior segment
      inflammation associated with heavy liquids. DESIGN: Observational case report.
      METHODS: Review of clinical and histopathologic changes. RESULTS: A 65-year-old
      patient underwent a pars plana vitrectomy for a rhegmatogenous retinal
      detachment. Perfluorodecalin was used as a temporary retinal tamponade. After
      surgery, bubbles of heavy liquid were noted in the anterior chamber. Fifteen
      months later, severe corneal edema developed, associated with corneal
      vascularization and keratic precipitates. Removal of heavy liquid through a
      paracentesis was attempted but the cornea remained edematous, and a penetrating
      keratoplasty was performed. In the histopathologic examination inflammatory
      changes from retention of perfluorodecalin were observed. There was a
      decompensated cornea with florid bullous keratopathy, inflammatory infiltration
      with vascularization, and deposition of perfluorodecalin within keratocytes and
      perivascular macrophages. CONCLUSION: Presence of heavy liquids in the anterior
      chamber may be associated with an intense inflammatory response and corneal
      decompensation.

PMID- 16086961
TI  - Ciliary body thickness increases with increasing axial myopia.
AB  - PURPOSE: To assess the relationship between ciliary body thickness and refractive
      error. DESIGN: Prospective observational case series. METHODS: We enrolled 75
      eyes of 75 patients with no history of intraocular surgery or use of anti
      glaucoma medication. Axial length was measured by A-scan ultrasonography. Ciliary
      body thickness (CBT) was measured by two masked observers on radial-section
      images of the temporal corneoscleral limbus, acquired with ultrasound
      biomicroscopy (UBM) at 2 and 3 mm posterior to the scleral spur (CBT2 and CBT3,
      respectively). RESULTS: Refractive error was inversely correlated with CBT2 and
      CBT3 (r = -.64 and r = -.52, P < .0001, respectively). Axial length was
      correlated with CBT (r = .66 and r = .57, P < .0001, for CBT2 and CBT3,
      respectively). CONCLUSION: CBT increases with increasing myopia and axial length.

PMID- 16086962
TI  - Canalicular and nasolacrimal duct blockage: an ocular side effect associated with
      the antineoplastic drug S-1.
AB  - PURPOSE: To report canalicular stenosis as a side effect of the new
      antineoplastic agent S-1. DESIGN: Interventional case series. METHODS: Three
      patients who received S-1 for treatment of gastrointestinal cancer at a tertiary
      cancer center were evaluated and treated for epiphora. RESULTS: Two patients were
      found to have severe canalicular stenosis and nasolacrimal duct blockage after
      approximately 6 months of S-1 therapy. One patient underwent
      dacryocystorhinostomy with silicone tube placement on one side and
      dacryocystorhinostomy and Pyrex glass tube placement on the other side. The other
      patient declined a surgical intervention. One additional patient with epiphora
      had punctal stenosis early in the course of S-1 therapy. His epiphora resolved
      after probing and irrigation and 4 weeks of topical corticosteroid therapy.
      CONCLUSIONS: Canalicular and nasolacrimal duct blockage is a previously
      unreported side effect of S-1 and should be recognized and treated at its
      earliest possible stage so that complete closure of the canaliculi can be
      avoided.

PMID- 16086964
TI  - Measurement of scleral thickness in uveal effusion syndrome.
AB  - PURPOSE: To measure scleral thickness in patients with and without uveal effusion
      syndrome using ultrasound biomicroscopy (UBM) and magnetic resonance imaging
      (MRI). DESIGN: Prospective case-control study. METHODS: UBM was used to measure
      scleral thickness in five subjects with uveal effusion syndrome and five matched
      controls. We also used MRI to measure scleral thickness in three subjects.
      RESULTS: The mean thicknesses for eyes with uveal effusion syndrome versus
      control eyes were 0.65 +/- 0.08 mm and 0.55 +/- 0.05 mm, respectively (mean
      difference 0.10, P value = .13). MRI measurements of three subjects showed
      abnormally thick sclera but were imprecise. CONCLUSIONS: UBM can be used to
      measure scleral thickness, and our results support the finding that patients with
      uveal effusion syndrome have abnormally thick sclera. Compared with MRI, UBM may
      be a more accurate and precise method of measuring scleral thickness. UBM can be
      a useful adjunctive test in the management of uveal effusion syndrome.

PMID- 16086963
TI  - Bilateral orbital tumor as initial presenting sign in human T-cell leukemia virus
      1 associated adult T-cell leukemia/lymphoma.
AB  - PURPOSE: To report a case of human T-cell leukemia virus type1 (HTLV-1)
      associated adult T-cell leukemia/lymphoma (ATLL) whose initial sign was
      exophthalmos. DESIGN: Case report. METHODS: A 64-year-old Japanese man presented
      with exophthalmos and choroidal folds of the right eye without general symptoms
      and received ophthalmologic and laboratory examination, magnetic resonance
      imaging (MRI), and orbital biopsy. RESULTS: Antibodies against HTLV-1 were
      extremely high but atypical lymphocytes were not present in the peripheral blood.
      MRI showed multiple tumorous lesions in both orbits. Orbital biopsy revealed an
      orbital mass that consisted of atypical lymphocytes originally from T cells and
      established the diagnosis of lymphoadenopathy type of ATLL. CONCLUSION: Although
      ocular involvement by ATLL is extremely rare, ATLL can first present in the
      orbit, and only the results of a biopsy can provide definitive information for
      its diagnosis.

PMID- 16086965
TI  - Surgical management of traumatic macular hole-related retinal detachment.
AB  - PURPOSE: To investigate the clinical characteristics and surgical outcome of
      traumatic macular hole-related retinal detachment. DESIGN: Retrospective,
      interventional case series. METHODS: Eight eyes of eight patients with traumatic
      macular hole-related retinal detachment underwent vitrectomy combined with gas
      tamponade, either initially or subsequently. Anatomic re-attachment of the
      retina, closure of traumatic macular hole, and visual outcome were measured.
      RESULTS: Successful retinal re-attachment was achieved in seven eyes (87.5%), and
      the macular hole was successfully closed in all eyes (100%). Improved vision
      after the surgery was noted in five eyes (62.5%), whereas three eyes (37.5%)
      displayed no change. CONCLUSIONS: Vitrectomy combined with gas tamponade appears
      to give an effective anatomic re-attachment rate for traumatic macular hole
      related retinal detachment. The presence of peripheral retinal breaks, vitreous
      hemorrhage, or the extent of retinal detachment has no discernible significant
      influence on closure rate of macular hole and retinal re-attachment rate.

PMID- 16086966
TI  - Bilateral sequential photodynamic therapy for sub-retinal neovascularization with
      type 2A parafoveal telangiectasis.
AB  - PURPOSE: To report the results of repeated bilateral sequential photodynamic
      therapy (PDT) with verteporfin for sub-retinal neovascularization associated with
      parafoveal telengiectasia. DESIGN: Interventional case series. METHODS: Three
      patients (minimum of 6-month follow-up) were analyzed after bilateral sequential
      PDT for parafoveal telengiectasia-associated sub-retinal neovascularization.
      RESULTS: Mean age was 53.3 +/- 2.1 years. Mean and median follow-up duration were
      12.3 and 10 months, respectively. Mean initial Early Treatment of Diabetic
      Retinopathy Study chart letter acuity was 30.6 in right eyes and 19 in left eyes,
      and at month 6, it was 30.6 in right eyes and 22.3 in left eyes. All patients
      received bilateral treatment three times; one eye received a fourth treatment.
      The greatest linear diameter was between 2310 and 5400 microm. CONCLUSION: PDT is
      a viable treatment for sub-retinal neovascularization associated with parafoveal
      telengiectasia. Bilateral sequential treatment is a convenient way to treat
      bilateral disease.

PMID- 16086967
TI  - B-Cells in ocular adnexal lymphoproliferative lesions express B-cell attracting
      chemokine 1 (CXCL13).
AB  - PURPOSE: The homeostatic chemokine, B cell attracting chemokine 1 (CXCL13), has
      been implicated in the pathogenesis of lymphocyte-mediated diseases. We
      investigated the cellular expression of this chemokine in the spectrum of ocular
      adnexal lymphoproliferative lesions. DESIGN: Laboratory investigation. METHODS:
      CXCL13 expression in paraffin-embedded adnexal biopsy specimens was determined by
      indirect immunohistochemistry with antigen retrieval. RESULTS: In 15 of 16 biopsy
      specimens, including reactive lymphoid hyperplasia (n = 7), atypical lymphoid
      hyperplasia (n = 3), and B cell lymphoma (n = 6), CXCL13 was detected. CD20
      positive B-cells, as well as dendritic cells and endothelial cells, expressed the
      chemokine. CONCLUSIONS: B-cells in ocular adnexal lymphoproliferative lesions
      demonstrate expression of CXCL13, a chemokine that may participate in tumor
      pathogenesis and is a potential target for novel therapies.

PMID- 16086969
TI  - Complications following ex-press glaucoma shunt implantation.
AB  - PURPOSE: To report post-operative course and complications in patients who
      underwent Ex-Press glaucoma shunt placement. DESIGN: Small case series. METHODS:
      Four patients were referred for management following Ex-Press shunt implantation.
      Patients underwent complete ophthalmologic evaluation and were appropriately
      managed. RESULTS: Of the four patients, two had inadequate control of intraocular
      pressure related to bleb failure caused by subconjunctival scar tissue formation.
      One patient experienced suprachoroidal hemorrhage 5 days after shunt placement
      followed a year later with conjunctival erosion and shunt rim exposure.
      Endophthalmitis from conjunctival erosion over the Ex-Press shunt rim was
      observed in one patient. CONCLUSION: Patients with subconjunctival implantation
      of the Ex-Press shunt should be monitored closely for possible conjunctival
      erosion that can lead to endophthalmitis and failure from fibrosis.

PMID- 16086968
TI  - Carcinosarcoma of the lacrimal gland arising from a pleomorphic adenoma.
AB  - PURPOSE: To report a case of the lacrimal gland tumor diagnosed as carcinosarcoma
      (true mixed tumor) arising from a pleomorphic adenoma. DESIGN: Interventional
      case report. METHODS: An 80-year-old Japanese woman was referred with a well
      circumscribed tumor in the lacrimal fossa. RESULTS: The tumor was excised, but
      the deepest portion remained because of heavy bleeding. Histopathologically, the
      tumor consisted of osteosarcomatous cells. No epithelial or myoepithelial
      component was identified by immunohistochemistry. Two months later, the tumor
      progressed further and was excised completely with lateral orbitotomy. The tumor
      consisted primarily of osteosarcomatous component but also had epithelial
      components including carcinoma and pleomorphic adenoma. Examinations did not
      detect local recurrence and metastasis at 10 post-operative months. CONCLUSION:
      The tumor was diagnosed as true carcinosarcoma of the lacrimal gland arising from
      a pleomorphic adenoma. When lacrimal gland tumors containing sarcomatous
      components are encountered, carcinosarcoma should be included in the differential
      diagnosis.

PMID- 16086970
TI  - Accommodative intraocular lens tilting.
AB  - PURPOSE: To report an unusual complication of accommodative intraocular lens
      (IOL) implantation after clear lens extraction for hyperopia correction. DESIGN:
      Observational case report. METHOD: A 48-year-old woman underwent clear lens
      exchange for the correction of moderate hyperopia. A Crystalens Model AT-45
      Accommodating Posterior Chamber IOL (AT-45 IOL) was implanted to allow optimal
      distance and near vision. At the 3-week follow-up appointment, she complained of
      monocular diplopia. Ocular examination showed an increased astigmatism, causing
      decreased visual acuity. Scheimpflug Pentacam Image and Wave Front Analysis
      supported the diagnosis of IOL tilting. RESULTS: IOL repositioning was
      unsuccessful because of fibrosis of the haptics. It was necessary to replace AT
      45 IOL with a monofocal acrylic sulcus-fixated IOL. CONCLUSION: Control of
      capsular fibrosis should be a major concern, especially in this type of IOL.
      Accommodating IOL exchange appears to be a safe alternative to manage this
      complication.

PMID- 16086971
TI  - Chart documentation by general physicians of the glaucoma medications taken by
      their patients.
AB  - PURPOSE: To estimate the frequency of documentation of glaucoma medications by
      primary care physicians. DESIGN: Cross-sectional, observational study. METHODS:
      The general medical records of 100 patients of one glaucoma specialist were
      reviewed. We recorded whether the mention of eyedrops appeared in the medical
      record. RESULTS: The median number of glaucoma medications used was 2.5 (range 1
      to 5). Fifty-five (55%, 95% confidence interval: 45%-65%) of the medical records
      of the primary physicians mentioned eyedrops. Alpha-agonists were statistically
      less frequently documented (13%) in the general medical record than beta
      adrenergic blockers (47%) and prostaglandins (44%). CONCLUSION: Almost half of
      the charts of these primary physicians had no documentation of any eyedrop use by
      their patients with glaucoma. An important step in reducing drug-induced side
      effects and interactions with other medications would be better recognition by
      primary physicians of the ophthalmic drugs used by their patients.

PMID- 16086972
TI  - Testing distance stereoacuity with the Frisby-Davis 2 (FD2) test.

PMID- 16086974
TI  - Twice-yearly exams unnecessary for patients taking quetiapine.

PMID- 16086976
TI  - Evaluation of image artifact produced by optical coherence tomography of retinal
      pathology.

PMID- 16086977
TI  - Automated measurements of retinal thickness with optical coherence tomography.

PMID- 16086979
TI  - The clinical effectiveness of cognitive behaviour therapy: outcome for a large
      sample of adults treated in routine practice.
AB  - There is increasing interest in questions about how far the demonstrated efficacy
      of psychological therapies in research trials can be translated into clinical
      effectiveness in routine practice. This paper summarises outcome data from
      several hundred patients treated with CBT in routine clinical practice in a
      National Health Service psychology service, and compares their outcomes with some
      of the published research. Although the data have flaws common in ordinary
      clinical practice (no untreated controls, missing data, uncontrolled
      pharmacotherapy, etc.), the analyses suggest that CBT in this context is an
      effective treatment, albeit with probably not quite such good results as it
      achieves in research trials. Using clinical significance statistics on
      standardised measures, about half of the sample reliably improved over a course
      of therapy, including about a third who recovered to normal range.

PMID- 16086980
TI  - Offspring of anxious parents: reactivity, habituation, and anxiety-proneness.
AB  - Reactivity and habituation patterns were examined in the offspring of anxious and
      non-anxious parents. Although no differences emerged for magnitude of response to
      either fear-relevant visual or auditory stimuli, offspring of anxious parents
      displayed significantly more electrodermal activity during resting baseline and
      during the inter-trial intervals of these stimulus presentations. Differences
      also were observed for the number of children per group achieving habituation to
      the fear-relevant visual and auditory stimuli, where offspring of anxious parents
      were less likely to habituate to either stimuli. The same pattern of group
      differences emerged after excluding children diagnosed with an anxiety disorder,
      indicating that even offspring of anxious parents who did not have an anxiety
      disorder differ from offspring of normal controls with respect to their pattern
      of psychophysiological reactivity. It is hypothesized that these features might
      serve as an indication of anxiety proneness and risk for the development of
      anxiety disorders.

PMID- 16086981
TI  - Preliminary evidence for an emotion dysregulation model of generalized anxiety
      disorder.
AB  - Three studies provide preliminary support for an emotion dysregulation model of
      generalized anxiety disorder (GAD). In study 1, students with GAD reported
      heightened intensity of emotions, poorer understanding of emotions, greater
      negative reactivity to emotional experience, and less ability to self-soothe
      after negative emotions than controls. A composite emotion regulation score
      significantly predicted the presence of GAD, after controlling for worry,
      anxiety, and depressive symptoms. In study 2, these findings were largely
      replicated with a clinical sample. In study 3, students with GAD, but not
      controls, displayed greater increases in self-reported physiological symptoms
      after listening to emotion-inducing music than after neutral mood induction.
      Further, GAD participants had more difficulty managing their emotional reactions.
      Implications for GAD and psychopathology in general are discussed.

PMID- 16086982
TI  - Does coping predict CO2-induced panic in patients with panic disorder?
AB  - Patients with panic disorder (PD) show maladaptive coping but the role of coping
      in the pathogenesis of panic is unclear. This study examined general coping and
      panic-specific coping as predictors of fear responding to CO2 inhalation.
      Subjective and physiological responses including panic attacks were assessed in
      45 patients with PD and 45 matched nonclinical controls. Measures of coping were
      the primary predictors used in the analyses. Consistent with other reports,
      patients with PD reported increased emotion-focused coping and there was an
      association between emotion-focused coping and subjective reactivity. However,
      only panic-specific coping predicted panic attacks in response to the CO2
      challenge.

PMID- 16086983
TI  - Treatment of panic disorder: live therapy vs. self-help via the Internet.
AB  - A randomized trial was conducted comparing 10 individual weekly sessions of
      cognitive behaviour therapy for panic disorder (PD) with or without agoraphobia
      with a 10-module self-help program on the Internet. After confirming the PD
      diagnosis with an in-person structured clinical interview (SCID) 49 participants
      were randomized. Overall, the results suggest that Internet-administered self
      help plus minimal therapist contact via e-mail can be equally effective as
      traditional individual cognitive behaviour therapy. Composite within-group effect
      sizes were high in both groups, while the between-group effect size was small
      (Cohen's d=16). One-year follow-up confirmed the results, with a within-group
      effect size of Cohen's d=0.80 for the Internet group and d=0.93 for the live
      group. The results from this study generally provide evidence to support the
      continued use and development of Internet-distributed self-help programs.

PMID- 16086984
TI  - Acceptance-based treatment for persons with complex, long standing chronic pain:
      a preliminary analysis of treatment outcome in comparison to a waiting phase.
AB  - The concept of acceptance is receiving increased attention as an alternate
      approach to the suffering that is often associated with persistent and disabling
      pain. This approach differs from established treatments in that it does not
      principally focus on reducing pain, but on reducing the distressing and disabling
      influences of pain as they concern important areas in patients' lives. The
      present analyses represent a preliminary evaluation of an acceptance-based
      approach to chronic pain within an interdisciplinary treatment program. One
      hundred and eight patients with complex chronic pain conditions completed
      treatment and provided data for the current study. Treatment was conducted in a 3
      or 4-week residential or hospital-based format. It included a number of exposure
      based, experiential, and other behavior change methods focused on increasing (a)
      engagement in daily activity regardless of pain and (b) willingness to have pain
      present without responding to it. Significant improvements in emotional, social,
      and physical functioning, and healthcare use were demonstrated following
      treatment. The majority of improvements continued at 3-months post-treatment.
      Improvements in most outcomes during treatment were correlated with increases in
      acceptance, supporting the proposed process of treatment.

PMID- 16086985
TI  - Effects of varied-stimulus exposure on overpredictions of pain and behavioural
      performance in low back pain patients.
AB  - The main objective of the present study was to investigate the benefits of
      exposure to a variety of movements versus exposure to the same movements on
      overprediction of pain and behavioural performance on a final behavioural test in
      a sample of chronic low back pain (CLBP) patients. Eighty-four CLBP patients were
      requested to perform four behavioural tests. Patients were assigned to two
      experimental conditions. The final behavioural test was the same for all
      patients. The first three behavioural tests consisted of three different
      movements in condition 1 and of three times the same movement in condition 2.
      During each behavioural test, baseline pain, expected pain and experienced pain
      were recorded. Furthermore, the peak torque and the variability of the produced
      muscle strength during the final behavioural test were assessed. Replicating and
      extending previous research, we found that patients overpredicted pain during a
      threatening behavioural test. Furthermore, pain-related fear and pain
      catastrophizing showed to be unique predictors of the peak torque of the final
      behavioural test. No support was found for our hypothesis that varied exposure
      facilitates generalization of exposure effects. Possible reasons for the failure
      to find an advantageous effect of varied-stimulus exposure and ideas for future
      research are discussed.

PMID- 16086986
TI  - Feared identity and obsessive-compulsive disorder.
AB  - We tested predictions from cognitive-behavioural theory that people with
      obsessive-compulsive disorder (OCD) regard their intrusions as revealing
      unacceptable aspects of their character. We compared an OCD sample with anxious
      controls (AC) and non-anxious controls (NAC) on a measure of the extent to which
      intrusions led to negative inferences about the self, assessed the discrepancy
      between their actual and feared self, and recorded the traits making up the
      feared self. The OCD sample did not differ from AC on self-discrepancies, but did
      differ from both control groups on the measure of negative inferences about the
      self. In addition, the feared self of the OCD sample was significantly more
      likely to consist of bad and immoral traits.

PMID- 16086987
TI  - Threat interpretation in anxious children and their mothers: comparison with
      nonclinical children and the effects of treatment.
AB  - Interpretation biases towards threat play a prominent role in cognitive theories
      of anxiety, and have been identified amongst highly anxious adults and children.
      Little is known, however, about the development of these cognitive biases
      although family processes have been implicated. The current study investigated
      the nature of threat interpretation of anxious children and their mothers through
      (i) comparison of a clinic and non-clinic population, (ii) analysis of individual
      differences; and (iii) pre- and post-treatment comparisons. Participants were 27
      children with a primary anxiety disorder and 33 children from a non-clinic
      population and their mothers. Children and mothers completed self-report measures
      of anxiety and indicated their most likely interpretation of ambiguous scenarios.
      Clinic and non-clinical groups differed significantly on measures of threat
      interpretation. Furthermore, mothers' and children's threat interpretation
      correlated significantly. Following treatment for child anxiety, both children
      and their mothers reported a reduction in threat interpretation.

PMID- 16086988
TI  - Amnesia, traumatic brain injury, and posttraumatic stress disorder: a
      methodological inquiry.
AB  - This study explored the relationship between mild traumatic brain injury (MTBI),
      amnesia, and posttraumatic stress disorder (PTSD). MTBI status and amnesia for
      the event were assessed in 307 consecutive admissions to a Level 1 Trauma Center.
      Amnesia did not always occur concurrently with MTBI: 18% of those with MTBI had
      full recall and over half had partial recall of the event. Just over 10% of
      participants developed PTSD by 12 months post-injury, with prevalence comparable
      across MTBI and non-MTBI groups. Non-significant differences in incidence of PTSD
      were apparent between those with full recall (9%), partial recall (14%) and no
      recall (7%). These data highlight the fact that PTSD may develop following trauma
      despite amnesia for the event, and illustrate the importance in both clinical and
      research settings of carefully examining the extent of amnesia.

PMID- 16086989
TI  - Nerve fibre and sensory end organ density in the epidermis and papillary dermis
      of the human hand.
AB  - Quantification of sensory recovery after peripheral nerve surgery is difficult
      and no accurate techniques are available at present. Quantification of
      reinnervated skin has been used experimentally, and in some clinical studies, but
      the lack of knowledge about the normal sensory distribution has been a problem.
      The purpose of this study was, therefore, to map the density of sensory end
      organs, nerve fibres and free nerve endings in the glabrous skin of the human
      hand. Skin biopsies were taken from patients undergoing acute and elective hand
      surgery. Nerve fibres were stained in the epidermis and papillary dermis and
      quantified in five sites on the palm of the hand, using protein gene product 9.5
      immunoreactivity-a panneuronal marker. The finger tip skin was found to have more
      than twice the nerve fibre density in the papillary dermis than the skin of the
      palm, and the number of Meissner corpuscles in the finger tip was also higher
      than in the palm. We found a reduction in innervation density with increasing age
      in the dermis, however, that was not the case for the epidermis. The innervation
      of the epidermis showed high interindividual variability and unlike the papillary
      dermis did not display any pattern of distribution in the hand.

PMID- 16086990
TI  - Do basal cell carcinomas recur after complete conventional surgical excision?
AB  - For 1378 patients treated in the 11 years 1988-1998 by conventional excision of
      1635 basal cell carcinomas, 1516 first index lesions were histologically
      completely excised. All patients having more than one BCC excised were identified
      from the data base from 1988 to 2003 to give minimum 5 years follow for last
      treated primary lesions in 1998. Measured clearance margins around the initial
      lesions at or near sites of presumptive recurrent lesions were noted and the
      lesions recorded photographically. All incompletely excised lesions whether or
      not re-excised were excluded. The median age for all patients was 70 years. Over
      minimum 5 years follow up, six patients developed nine subsequent lesions
      contiguous with the scar or graft repair of primary index lesion excision site
      (probable recurrences). The median interval to recurrence was 41 months (4 months
      8 years 10 months), with median lateral clearance margin around the primary
      tumour of 2 mm (0.3-6.8 mm). A further nine patients developed 11 new lesions
      near (within 1cm of) the scar or graft of primary index lesion excision site
      (possible recurrences). The median interval to recurrence was 59 months (1 year-8
      years 6 months). The median lateral clearance margin around the primary tumour
      was 4.1 mm (0.8-5.8 mm). For the two groups combined the maximum recurrence rate
      expressed as a percentage of index lesions was 1.3% (20/1516). Two thirds of
      possible and probable recurrences occurred in the temple and forehead, although
      these sites represented only 22% of all lesions, which may rather suggest new
      lesions in an area of field change as opposed to residual disease. The measured
      clearance margins reported here perhaps suggest that some original lesions may
      well have been completely excised primarily and many 'recurrences' were new
      primaries. These figures indicate there is a low order of probability for the
      incidence of recurrent basal cell carcinoma during minimum 5 years follow period
      after conventional surgical excision and conventional histological assessment of
      tumour resection margins.

PMID- 16086991
TI  - Use of the vertical rectus abdominis myocutaneous flap after abdominoplasty.
AB  - A vertical rectus abdominis myocutaneous flap was used to provide cover for a
      recurrent angiosarcoma in the abdominal skin. Of note, the patient had 9 years
      previously undergone formal abdominoplasty to allow closure following excision of
      the primary tumour. This flap is normally reliant on myocutaneous perforators
      originating from the deep epigastric system, which are divided during
      abdominoplasty. Despite this, the flap survived well, implying that a new blood
      supply had formed during the intervening years. This flap can, therefore, be
      considered a possible option in reconstructive cases where other options are
      limited, despite a preceding abdominoplasty. In the future because of the
      increasingly common occurrence of abdominoplasty in young females, this procedure
      may need to be considered.

PMID- 16086992
TI  - The sandwich omental flap for abdominal wall defect reconstruction.
AB  - We present a case of a large full thickness abdominal wall defect following
      excision of a huge basal cell carcinoma, uniquely reconstructed with a sandwich
      omental flap, vicryl/prolene (vypro II) mesh and split thickness skin graft.

PMID- 16086993
TI  - Pseudocyst formation after abdominal liposuction-extravasations of Morel-Lavallee
      on MR images.
AB  - A swelling of the abdominal wall in a 27-year-old woman after undergoing
      liposuction is described. Pseudocyst of Morel-Lavallee was located within the
      abdominal fascia and removed by surgery. MRI showed a non-homogenous mass with
      hyper intense fluid level and septations in T2-weighted images. We speculated
      that MRI can be used to guide the treatment (conservative or surgical). The
      literature concerning liposuction is reviewed.

PMID- 16086994
TI  - Skeletal muscle metastasis from malignant melanoma.
AB  - Malignant melanomas commonly metastasise to skin, subcutaneous tissue and lymph
      nodes. Skeletal muscle metastases from malignant neoplasms are uncommon. There
      have been very few reports of malignant melanoma metastasising to skeletal
      muscle. We report a case of malignant melanoma metastasis in the thigh
      musculature in a young female patient.

PMID- 16086995
TI  - Heterotopic nasopharyngeal brain tissue associated with cleft palate.
AB  - Heterotopic brain tissue in a cleft palate is a very rare developmental anomaly.
      We present the eighth case reported worldwide with a review of the literature and
      suggestions on the management of this unusual condition.

PMID- 16086996
TI  - Spontaneous regression of a rare tumour in a child: angiolymphoid hyperplasia
      with eosinophilia of the hand: case report and review of the literature.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign,
      idiopathic vasculoproliferative condition manifested by multiple or solitary
      subcutaneous nodules, usually in the head and neck region of young adults. It is
      very rare in the extremities especially in the hands. Although recurrence is
      common, surgical excision is still regarded as the treatment of choice. We report
      an 11-year-old girl with histologically confirmed ALHE on the dorsum of her left
      hand, which underwent complete spontaneous regression within 10 weeks.
      Angiolymphoid hyperplasia is a benign disease and it is important to recognise
      this condition so that early superficial lesions can be observed for 3-6 months
      pending spontaneous regression.

PMID- 16086997
TI  - Acute exacerbation of macroglossia.
AB  - We report the case of a large venous malformation of the tongue, preventing the
      patient from being able to contain it within the oral cavity. The extent of the
      malformation precluded a complete surgical excision. The immediate problems were;
      impending airway compromise, inability to speak, eat or drink, severe discomfort
      due to exposure-induced dryness and an embarrassing spectacle. This case
      demonstrates that even malformations considered to be incurable may be managed
      appropriately.

PMID- 16087000
TI  - Recent advances and future perspectives in the management of lung cancer.

PMID- 16087001
TI  - First record of Pseudomyicola spinosus in Argopecten ventricosus in Baja
      California, Mexico.
AB  - This is the first record of the copepod Pseudomyicola spinosus in the scallop
      Argopecten ventricosus in northwestern Mexico, and describes: (1) the known
      annual prevalence and intensity of this copepod on scallops from culture sites
      (Gulf of California) and natural populations (Pacific coast), (2) the
      histopathological effects caused on the soft tissues of scallops, and (3) the
      relationship between prevalence and intensity records and environmental
      parameters. The copepod was present throughout the period of investigation,
      showing similar prevalence and ratio of copepod to scallop patterns in both
      cultured scallops and wild specimens from natural habitats. Highest prevalence
      and ratio values were detected in summer-autumn at both sites, probably because
      scallops showed a weak condition from the combined effects of spawning,
      reabsorption of residual gametes, and high temperature. The condition index of A.
      ventricosus showed a significant correlation with the presence of the copepod in
      Magdalena Bay (-0.67). P. spinosus was observed in the gills of scallops,
      producing alterations or rupture of filaments, and in the stomach, causing
      detachment and loss of the epithelium. No relationship between copepod
      infestation with temperature, salinity, chlorophyll, and seston were found during
      the investigation. Although P. spinosus was present year-round at both sites, no
      association between infestation and scallop mortalities was detected.

PMID- 16087002
TI  - Effect of two strains of Flavescence doree phytoplasma on the survival and
      fecundity of the experimental leafhopper vector Euscelidius variegatus
      Kirschbaum.
AB  - We have investigated the influence on longevity and fecundity of Flavescence
      doree phytoplasma (FDP), the agent of a grapevine yellows disease, in the
      experimental vector Euscelidius variegatus Kirschbaum. Late instar nymphs were
      exposed to one or the other of two strains of FDP (FD92 and FD2000) by feeding on
      infected broad bean (Vicia faba L.) or on healthy broad bean or maize (Zea mays
      L.) for an acquisition access period of 13 days. Detection of FDP in individual
      insects was done with PCR assays and revealed that almost all exposed leafhoppers
      had acquired FDP, for both FD92 and FD2000 strains. FDP infection significantly
      reduced the life span of males and females (ANOVA of the quartiles of survival
      distribution and Weibull scale parameter). FDP-exposed females produced
      significantly fewer nymphs. The two FDP strains had similar effects on reduction
      of survival and fecundity of leafhoppers. There was no significant differences in
      longevity of E. variegatus males exposed to FD broad bean than held on healthy
      broad bean or maize, but female survival and fecundity were reduced when they fed
      on maize versus healthy broad bean.

PMID- 16087003
TI  - Ascosphaera aggregata contamination on alfalfa leafcutting bees in a loose cell
      incubation system.
AB  - The alfalfa leafcutting bee, a solitary bee used to pollinate alfalfa seed crops,
      is seriously affected by chalkbrood, a larval disease caused by the fungus
      Ascosphaera aggregata. One attempt to control the disease includes removing nests
      from the nesting boards (the "loose cell" system). We report here that adults
      emerging from the loose cells are heavily contaminated with A. aggregata spores.
      The contamination levels are not as high as previously reported for bees emerging
      directly from the boards, but they are still a likely focus for disease spread
      and may need to be targeted in chalkbrood control strategies.

PMID- 16087004
TI  - Laboratory bioassays of entomopathogenic fungi for control of Delia radicum (L.)
      larvae.
AB  - Laboratory soil bioassays were performed at economic field rates for in-furrow
      (3.85 x 10(6)spores/g dry soil) and broadcast (3.85 x 10(5)spores/g dry soil)
      applications with three isolates of Metarhizium anisopliae (F52, ATCC62176, and
      ARSEF5520) and one isolate of Beauveria bassiana (GHA). All isolates tested were
      infective to second instar Delia radicum (L.). The conditionally registered M.
      anisopliae isolate (F52) performed best killing an average of 85 and 72% of D.
      radicum larvae at the high and low concentration, respectively. The mean LC50 and
      LC95 of F52 against second instar D. radicum was 2.7 x 10(6) and 1.8 x
      10(8)spores/g dry soil, respectively. The use of F52 in an integrated management
      program is discussed.

PMID- 16087005
TI  - Qualitative assessment of surface topography of XeCl laser etched Ni-Cr alloy.
AB  - OBJECTIVES: The aims of this study were to compare the mode of debonding
      (adhesive or cohesive) of laser-etched Ni-Cr alloy (Wiron 99) to a standard
      sandblasting technique, and to a combination of sandblasting and laser etching.
      The etched surfaces were examined using optical and electron microscopy
      techniques. METHODS: Five groups of randomly allocated Ni-Cr cylinders were
      prepared: Group I-sandblasted; Groups II-IV-laser etched at three fluences (3.0,
      4.0 and 4.9 J/cm2), Group V-combination sandblasting and laser etching (4.0
      J/cm2). Within groups specimens were bonded into pairs (N=8) with composite
      luting cement (Panavia 21) prior to tensile debonding. Optical and scanning
      electron microscopy were performed both prior to and following debonding.
      RESULTS: An oxide layer was observed on sample surfaces before surface
      preparation by lasing or abrasion. Sandblasting removed the oxidation layer,
      which low and medium laser fluences alone failed to fully ablate. The highest
      (4.9 J/cm2) laser fluence melted the surface of the Ni-Cr alloy, covering the
      oxidation layer. A combination of sandblasting and lasing at 4.0 J/cm2 allowed
      full removal of the surface oxidation layer due to abrasion, followed by
      roughening of the surface with the laser. This resulted in greater mean tensile
      debonding strengths [Murray, A, Attrill, D, Dickinson, M. Dent Mater, 2004, In
      press] and a tendency for cohesive rather than adhesive interface failures.
      Groups I-IV underwent partial adhesive failure at both surfaces. Group V, in the
      main, underwent cohesive failure with a layer of adhesive remaining on both
      surfaces. SIGNIFICANCE: Laser etching of Ni-Cr alloy in combination with
      sandblasting optimises bonding to composite luting agents, resulting in a high
      proportion of cohesive failures when compared to sandblasting or lasing alone.

PMID- 16087007
TI  - A simple and valuable approach for measuring customer satisfaction.
AB  - OBJECTIVE: To determine the financial impact of poor customer satisfaction and
      the value of information gained from using a 1-question customer-satisfaction
      survey in a medical setting. STUDY DESIGN AND SETTING: A single-question customer
      satisfaction survey was collected from customers presenting to an academic
      otolaryngology head and neck surgery outpatient clinic. RESULTS: The overall
      response rate was 25%, overall net promoter score was 67.3%, lowest net promoter
      score occurred on Wednesday and Friday, overall net potential referrals were 872,
      and potential lost revenue from dissatisfied customers equaled US 2.3 million
      dollars. CONCLUSION: A single-question customer-satisfaction survey may help
      identify areas of customer dissatisfaction that lead to a significant source of
      lost revenue. SIGNIFICANCE: The competitive forces in today's health care
      environment require medical practices to address issues related to customer
      satisfaction.

PMID- 16087008
TI  - Symptom and disease severity differences between nasal septal deviation and
      chronic rhinosinusitis.
AB  - OBJECTIVE: To determine whether patients with chronic rhinosinusitis (CRS)
      exhibit more severe sinonasal symptom scores as compared with patients with nasal
      septal deviation (NSD) alone. METHODS: Two patient cohorts were prospectively
      identified: patients undergoing surgery for NSD alone and those undergoing
      endoscopic sinus surgery for CRS without NSD. Patients in the NSD group were
      required to have normal paranasal sinus CT scans, whereas patients in the CRS
      group were required to have radiographic evidence of CRS. All patients completed
      the Rhinosinusitis Symptom Inventory (RSI). Statistical comparisons were
      conducted between cohorts with respect to RSI symptom domains and medical
      resource utilization. RESULTS: A total of 42 patients were identified in the NSD
      group (mean age, 40.8 years) and 155 patients were identified in the CRS group
      (mean age, 44.9). Patients with CRS demonstrated higher severity scores for the
      nasal symptom domains (60.3 [CRS] versus 53.9 [NSD], P = 0.037). Oropharyngeal
      symptoms and total symptoms were also worse for the CRS group versus the NSD
      group (29.8 versus 23.1, P = 0.014 and 43.0 versus 37.0, P = 0.030). Facial and
      systemic symptom scores did not differ between groups. Patients with CRS
      demonstrated significantly higher utilization rates for topical nasal steroids
      (21.2 versus 12.2 weeks, P = 0.006) and oral antibiotics (7.9 weeks versus 2.1
      weeks, P < 0.001), but not for oral antihistamines (P = 0.420). CONCLUSIONS:
      Although patients with CRS manifest higher sinonasal symptom scores than patients
      with NSD alone, differentiating these 2 diagnoses on the basis of symptoms alone
      is difficult. These data suggest that as a disease process, CRS confers a
      significant disease burden with more significant negative symptom impact.

PMID- 16087009
TI  - Unilateral opacification of paranasal sinus CT scans.
AB  - OBJECTIVES: The aim of study was to describe the histopathology in patients with
      unilateral sinus opacification and to identify variables that may predict
      neoplastic pathology. STUDY DESIGN: A retrospective review of paranasal sinus CT
      scans performed between 2000 and 2003 was conducted to identify patients with
      unilateral sinus opacification. RESULTS: Twenty-eight of 1118 CT scans showed
      unilateral sinus opacification. Twelve patients had neoplastic disease, 13 had
      inflammatory disease. Nasal discharge was more common in inflammatory than
      neoplastic disease (P = 0.009). A polyp or mass lesion was more common on
      nasendoscopy in neoplastic than inflammatory disease (P = 0.01). Bony erosion was
      only identified in malignant disease. CONCLUSION: A wide variety of pathologies
      present with unilateral sinus opacification on CT scanning. In our series,
      neoplastic disease was more associated with a visible polyp or mass lesion and
      less with nasal discharge. Bony erosion on CT scan was only seen in malignant
      disease. Histologic confirmation remains obligatory for diagnosis.

PMID- 16087010
TI  - Prevalence of pus in radiologically diseased sinuses in patients undergoing
      surgery for chronic rhinosinusitis.
AB  - OBJECTIVE: To establish the prevalence of pus in radiologically diseased sinuses
      in patients undergoing sinus surgery and to correlate this with the bacterial
      load in the sinuses. STUDY DESIGN AND SETTING: A prospective study performed on
      adult patients with the diagnosis of chronic sinusitis undergoing endoscopic
      sinus surgery at an Adelaide group of academic hospitals. In 45 consecutive and
      unselected patients, a radiologically diseased sinus was surgically opened, and a
      specially designed suction aspirator was placed into the sinus under endoscopic
      control. These aspirates were Gram stained and cultured to quantify the
      polymorphonuclear neutrophil count, bacterial flora, and bacterial colony count.
      The CT scans of all patients were graded by using the Lund-Mackay scoring system.
      RESULTS: A variety of bacteria, most commonly staphylococci, were cultured from a
      radiologically diseased sinus in 88% of patients. There was no correlation
      between the bacterial colony count and presence of pus, and only 11% of patients
      had microscopic evidence of inflammation in sinus aspirates. There was no
      correlation between the Lund-Mackay CT score and the presence of pus in the
      sinus. CONCLUSIONS: The majority of patients undergoing surgery for chronic
      sinusitis did not have a purulent exudate, and there was no correlation with the
      bacterial load. The usefulness of antibiotics in the treatment of chronic
      rhinosinusitis, in the absence of macroscopic pus, is questionable.

PMID- 16087011
TI  - Orbital decompression in graves' ophthalmopathy by medial and lateral wall
      removal.
AB  - OBJECTIVE: The objective of this study is to describe a technique for balanced
      orbital decompression and to analyze the results. METHODS AND MATERIALS: We
      conducted a retrospective study of 140 patients (276 orbits). Orbital
      decompression was carried out by removal of the medial orbital wall by
      ethmoidectomy and complete removal of the lateral wall by bringing out the entire
      sphenoid wing together with part of the zygomatic bone down to the inferior
      orbital fissure. RESULTS: One hundred thirty-six patients underwent bilateral
      decompression, 4 patients underwent monolateral decompression. Proptosis was
      reduced on average by 5.3 mm; 28 (20%) patients showed onset or worsening of
      diplopia. CONCLUSIONS: Medial and lateral approach allows a balanced orbital
      decompression. As some patients may present different degrees of proptosis and
      visual impairment, we stress the importance of carefully weighing the
      preoperative conditions of the individual patient when choosing the surgical
      approach.

PMID- 16087012
TI  - What is the relationship between chronic sinus disease and isolated nasal septal
      deviation?
AB  - OBJECTIVE: The aim of this retrospective study is to examine the role of isolated
      nasal septal deviation (NSD) in the pathogenesis of chronic rhinosinusitis (CRS).
      STUDY DESIGN AND SETTING: The interaction between isolated NSD and chronic sinus
      disease were retrospectively evaluated in 1452 patients. Out of 1452 patients,
      152 patients were included in the study. Patients with anatomical variants other
      than NSD were excluded from the study. Patients with NSD were enrolled in the
      study group and patients without NSD were enrolled in the control group. RESULTS:
      There was no statistically significant difference between NSD group and non-NSD
      group with respect to the CRS. CONCLUSIONS: The mild to moderate degree of NSD
      was not a risk factor for chronic sinus disease. Only gross deviation of the
      nasal septum itself is a risk factor for the development of CRS. SIGNIFICANCE:
      Excluding the subjects with ostiomeatal anatomic variations has differentiated
      this study from the previously reported researches (isolated NSD).

PMID- 16087013
TI  - Efficacy and safety of a novel, single-dose azithromycin microsphere formulation
      versus 10 days of levofloxacin for the treatment of acute bacterial sinusitis in
      adults.
AB  - OBJECTIVE: To compare the efficacy and safety of a single 2.0-g dose of a novel
      azithromycin microsphere formulation with that of 10 days of levofloxacin, 500
      mg/d, when used to treat adults with uncomplicated acute bacterial maxillary
      sinusitis (ABS). STUDY DESIGN AND SETTING: An international, multicenter,
      randomized, double-blind, double-dummy trial. Eligible outpatients > or =18 years
      of age with clinical and radiographic evidence of ABS underwent maxillary sinus
      aspiration before randomization. Primary endpoint was clinical efficacy at the
      test-of-cure visit (day 17-24). RESULTS: Clinical success rates were 94.5%
      (242/256) in azithromycin-microspheres-treated patients and 92.8% (233/251) in
      the levofloxacin group. In patients with documented Streptococcus pneumoniae,
      Haemophilus influenzae, or Moraxella catarrhalis, clinical cure rates were 97.3%
      (36/37), 96.3% (26/27), and 100% (8/8), respectively, for the azithromycin group
      and 92.3% (36/39), 100% (30/30), and 90.9% (10/11), respectively, for the
      levofloxacin group. CONCLUSIONS: Single-dose azithromycin microspheres provided
      clinical and bacteriologic efficacy and safety comparable to 10 days of
      levofloxacin. SIGNIFICANCE: A novel microsphere formulation of azithromycin given
      as a single dose was safe and effective for the treatment of ABS.

PMID- 16087014
TI  - Editorial commentary: dilemma in trial design: do current study designs
      adequately evaluate effectiveness antibiotic in ABRS?

PMID- 16087015
TI  - Does hydrogen peroxide mouthwash improve the outcome of secondary post
      tonsillectomy bleed? A 10-year review.
AB  - OBJECTIVE: To determine whether hydrogen peroxide (H(2)O(2)) mouthwash influences
      the outcome of secondary post-tonsillectomy hemorrhage in children. STUDY DESIGN:
      Ten-year retrospective study of all children with secondary post-tonsillectomy
      hemorrhage. SETTING: Tertiary otolaryngology center. RESULTS: Of the 156
      patients, 59 received H(2)O(2) and 97 did not. All patients received broad
      spectrum intravenous antibiotics. The average rehospitalization duration due to
      hemorrhage was 1.7 days (H(2)O(2) group) and 1.6 days (control group). In the
      H(2)O(2) group, 8.5% required surgery, compared with 10.3% in the control group.
      Further hemorrhage episodes requiring readmission occurred in 3.4% of the
      H(2)O(2) group and 3.1% of controls. There was no difference between the 2 groups
      in rehospitalization duration (P = 0.49), rate of surgical intervention (P =
      0.85), and rate of readmission with further hemorrhage (P = 0.92). CONCLUSION:
      Hydrogen peroxide mouthwash does not improve the outcome of secondary post
      tonsillectomy hemorrhage in pediatric patients. SIGNIFICANCE: This study does not
      support the common practice of treating post-tonsillectomy hemorrhage with
      H(2)O(2).

PMID- 16087016
TI  - Penicillin reduces eustachian tube gland tissue changes in acute otitis media.
AB  - OBJECTIVE: The volume of the mucous paratubal glands and the number of the mucus
      producing goblet cells in the middle ear and Eustachian tube (ET) are increased
      after experimental acute otitis media (AOM). The present investigation examines a
      potential effect of penicillin on the changes in goblet cell density and gland
      structures of the ET during and after AOM. STUDY DESIGN: Middle ear inoculation
      of Streptococcus pneumoniae in 50 rats. Two days later, 25 rats were given
      penicillin V as one daily dose for 5 days. Twenty-five rats received no
      treatment. Five animals from each group were sacrificed on days 4, 8, 16, 90, and
      180. The ET was dissected and decalcified, followed by paraffin embedding, serial
      transverse sectioning, and PAS/alcian blue staining. The goblet cell density and
      the paratubal gland composition and volume were determined in every 20th section,
      using a light microscope. RESULTS: Penicillin reduced the increase of goblet cell
      density from day 8 and through 6 months, whereas the increase of the paratubal
      mucous gland volume was unaffected by treatment. CONCLUSION: We conclude that
      penicillin reduces the increase of ET goblet cell density during and after acute
      otitis media, whereas the paratubal gland volume remains unaffected. An increased
      mucosal secretory capacity and indicated excessive secretion of mucus may
      contribute to the deteriorated ET function found after AOM and thus predispose,
      sustain, or aggravate middle ear disease. This may be prevented by penicillin
      treatment.

PMID- 16087017
TI  - Transpalatal advancement pharyngoplasty outcomes compared with
      uvulopalatopharygoplasty.
AB  - OBJECTIVE: Uvulopalatopharyngoplasty (UPPP) success rates in patients classified
      with Friedman stage 3 is reported as 8%. Surgical failure may result from
      persistent obstruction at the palate, which may be addressed by pharyngoplasty
      with palatal advancement (PA). The effectiveness of PA versus UPPP was evaluated
      by using polysomnographic outcomes in a retrospective cohort of patients
      classified with Friedman stage 3. METHODS: Surgical records were reviewed for PA
      (n = 47) and UPPP (n = 124). Clinical records were reviewed and reclassified by
      Friedman stage. Respiratory data were collected from overnight polysomnography.
      Statistical analysis was conducted of continuous variables (ANOVA), categorical
      variables (chi2), and adjusted odds ratios by using logistic regression. RESULTS:
      PA (n = 30) and UPPP (n = 44) did not differ in baseline apnea hypopnea index
      (AHI), age, or BMI. Both PA (48.3 +/- 24.6 to 19.8 +/- 16.8 events per hour, P <
      0.000) and UPPP (47.9 +/- 30.0 to 30.9 +/- 24.2 events per hour, P < 0.000)
      improved with surgery. In the PA group, final AHI was lower (17.1 +/- 30.1 versus
      28.5 +/- 25.6, P < 0.04) and postoperative change was greater (30.9 +/- 24.2
      versus 19.8 +/- 16.8, P < 0.02). For patients with Friedman stage 3, odds ratio
      of having an AHI of <20 events per hour and a greater than 50% reduction with PA
      compared with UPPP was 3.80 (95% CI, 1.41-10.29, P < 0.013). Adjusted for age,
      body mass index, preoperative apnea severity, and tongue-base surgery, OR was
      5.77 (95% CI of 1.80-17.98). CONCLUSIONS: Polysomnographic outcomes using AHI
      support the use of palatopharyngoplasty using palatal advancement as an effective
      treatment of obstructive sleep apnea. PA may offer benefit over UPPP alone in
      patients classified with Friedman stage 3.

PMID- 16087018
TI  - Tongue base suspension combined with UPPP in severe OSA patients.
AB  - OBJECTIVE: Tongue base surgery in the severe OSA patients may improve the success
      of uvulopalatopharyngoplasty (UPPP) as the collapse is multilevel. The aim of
      this study was to evaluate the long-term objective and subjective effectiveness
      of the minimally invasive tongue base suspension combined with UPPP in severe OSA
      patients. STUDY DESIGN AND SETTING: We conducted a retrospective analysis of 22
      OSA patients undergoing UPPP and the tongue base suspension for the treatment of
      severe OSA. RESULTS: Twenty-two men who had their preoperative and postoperative
      polysomnography had a 54% reduction in the preoperative Respiratory Disturbance
      Index (RDI), from 47.50 +/- 15.74 to a level of 17.31 +/- 14.17. The standard
      surgical cure rate which is a >50% reduction in the RDI and a postoperative RDI
      of <20 events/hour was 81.81%. All patients had some degree of subjective
      improvement in their snoring, daytime sleepiness, and the Epworth sleepiness
      scale. CONCLUSIONS: The tongue base suspension combined with UPPP has been shown
      to reduce RDI better than UPPP alone. This minimally invasive technique is highly
      successful at 81.81% when combined with UPPP in the severe OSA patients with
      multilevel airway collapse. SIGNIFICANCE: This study shows the benefits of
      minimally invasive tongue base suspension combined with UPPP in severe
      obstructive sleep apnea syndrome.

PMID- 16087019
TI  - Radiofrequency versus injection snoreplasty in simple snoring.
AB  - OBJECTIVE: To compare the efficacy and tolerance of controlled temperature
      radiofrequency (RF) and injection snoreplasty (IS) for the treatment of simple
      snoring. STUDY DESIGN: The study was a nonrandomized, prospective study conducted
      on 70 simple snorers. Efficacy of the operations was subjectively evaluated by
      the bed partners and after 6 weeks of the last treatment. Tolerance was evaluated
      by the patient during first 10 postoperative days. Postoperative pain and
      discomfort level were assessed. RESULTS: Satisfaction in terms of snoring
      severity was reported by 87.5% of the cases with RF and by 76.7% of the patients
      with IS. Discomfort levels also were similar for both groups CONCLUSIONS:
      Controlled-temperature RF and IS were both effective on snoring and well
      tolerated by the patients. This allows retreatments if necessary.

PMID- 16087020
TI  - Anatomic analysis of the Genial Bone Advancement Trephine System's effectiveness
      at capturing the genial tubercle and its muscular attachments.
AB  - OBJECTIVE: The Genial Bone Advancement Trephine (GBAT) System (Stryker Leibinger
      Inc, Kalamazoo, MI) is a 1-step system that advances the genial tubercle for
      treatment of retrolingual obstruction in obstructive sleep apnea. The purpose of
      this project was to anatomically analyze the effectiveness of the GBAT System to
      capture the genial tubercle and its muscular attachments in the circular
      trephine. METHODS: Eight cadaveric heads (ages 54-89 years; 3 female and 5 male)
      were examined, and Panorex radiographs (Stryker Leibinger Inc, Kalamazoo, MI)
      were obtained. Seven specimens were selected on the basis of mandibular height
      and dentition to undergo the procedure. The procedure was performed using the
      GBAT system with the 14-mm trephine according to the stepwise instructions. The
      mandibles were dissected, and analysis of the location of the osteotomy with
      respect to the genial tubercle, genioglossus muscles, geniohyoid muscles, and
      mandibular dentition was performed. RESULTS: All 7 of the specimens had complete
      capture of the genial tubercle. The mean percentage of the genioglossus muscle
      captured in the circular trephine was 85% (50%-100%). All specimens had
      preservation of the posterior muscle fibers. The mean percentage of the
      geniohyoid muscle captured was 78% (15%-100%). No tooth roots were transected or
      contained in the bone plug. CONCLUSIONS: The GBAT System is an effective 1-step
      system for capturing and advancing the genial tubercle and its muscular
      attachments in the treatment of OSA.

PMID- 16087021
TI  - Physiologic model of oropharyngeal swallowing revisited.
AB  - OBJECTIVE: The purposes of this investigation were to determine whether the
      temporal onsets of swallow events segment into oral and pharyngeal phases, to
      test the interdependence of temporal onsets of swallow events, and to determine
      the influence of age on total swallow duration. STUDY DESIGN AND SETTING: The
      onsets of swallowing and respiratory measures were studied in 76 healthy normal
      individuals. RESULTS: Confirmatory factor analysis revealed a 2-factor solution
      but did not support the hypothesized 2-phase structure (ie, oral and pharyngeal).
      Two of the onsets, apnea onset and apnea offset, formed a single factor that
      explained 12.6% of the variation among the 11 onset times. The other 9 onsets
      formed a second factor that explained 66.4% of the variation. Age accounted for
      modest variation in total swallow duration. CONCLUSIONS: The two factors,
      oropharyngeal and respiratory, explained 79% of the variation among the 11 onset
      times. SIGNIFICANCE: This finding speaks to the overlap between the initiation of
      oral and pharyngeal components of swallowing in adults and highlights the
      artificiality of separating the swallowing continuum into isolated phases.

PMID- 16087022
TI  - Bilateral congenital vocal cord paralysis: a 16-year institutional review.
AB  - OBJECTIVE: To review the management and outcome of bilateral congenital true
      vocal cord paralysis in 22 patients treated over a 16-year period and to review
      the role of tracheostomy in these patients. DESIGN: Retrospective chart review.
      SETTING: Pediatric tertiary hospital. PATIENTS: Twenty-two pediatric patients
      diagnosed with bilateral congenital true vocal cord paralysis. INTERVENTIONS:
      Flexible or rigid diagnostic evaluation, tracheostomy, and vocal cord
      lateralization procedures. MAIN OUTCOMES MEASURES: Vocal cord recovery and
      decannulation. RESULTS: With a mean follow up of 50 months, 15 of 22 patients
      (68%) with bilateral vocal cord paralysis required tracheostomy for airway
      securement. Of the 15 tracheotomized patients, 10 were successfully decannulated
      (8 had spontaneous recovery, whereas 2 required lateralization procedures).
      Eleven of these patients with tracheostomy had comorbid factors, including
      neurologic abnormalities (midbrain/brainstem dysgenesis, Arnold-Chiari
      malformation, global hypotonia, and developmental delay). Of the 7 patients not
      requiring tracheostomy, 6 recovered vocal cord function (86%). CONCLUSION: In our
      series of 22 patients with bilateral vocal cord paralysis, 14 had spontaneous
      recovery of function. Patients managed with tracheostomy were noted to have a
      high incidence of comorbid factors. In this series, recovery rates were found to
      be higher in nontracheostomized patients than in tracheostomized patients.
      Patients can be carefully selected for observation versus tracheostomy at the
      time of diagnosis based on underlying medical conditions.

PMID- 16087023
TI  - Pediatric tracheotomies in an Asian population: the Singapore experience.
AB  - OBJECTIVE: Over the past 2 decades, tracheotomy in children and infants has
      evolved from a primarily emergent procedure for upper airway obstruction into a
      semielective procedure for airway access in assisted ventilation. We present a 12
      year retrospective review of tracheotomies performed in the pediatric population
      in Singapore. STUDY DESIGN AND SETTING: We reviewed all tracheotomies performed
      in children below the age of 16 years in 2 tertiary pediatric medical centers in
      Singapore from January 1991 to December 2003. Indications for surgery are
      reviewed, and outcomes in terms of morbidity rate, mortality rate, postoperative
      rehabilitation, and duration of decannulation process were analyzed. RESULTS:
      Tracheotomies were performed in 48 children during the study period. The mean age
      of patients was 3.24 years, with ages ranging from 16 days to 14 years. Sixty
      three percent of tracheotomies were done within the 1st year of life. The chief
      indication was airway access for assisted ventilation. The overall complication
      rate was 31%. There were 13 attempts at decannulation, with 9 successes. No
      tracheotomy-related deaths occurred. CONCLUSION: Tracheotomy is a relatively safe
      procedure in children and infants. Lower decannulation rates and the evolving
      role of tracheotomy for early access in assisted ventilation permits earlier
      discharge with tracheotomy in situ.

PMID- 16087024
TI  - Intratympanic steroid injection for treatment of idiopathic sudden hearing loss.
AB  - OBJECTIVE: To conduct a clinical trial of intratympanic steroid injection for
      idiopathic sudden sensorineural hearing loss in subjects who failed oral steroid
      therapy. STUDY DESIGN AND SETTING: Open-label methylprednisolone injection
      clinical trial in a tertiary neurotologic referral center. Twenty subjects (14
      males; 6 females) received 4 injections within a 2-week period (4 days apart).
      Hearing, dizziness, and tinnitus were evaluated before and after treatment.
      RESULTS: There were no serious unexpected adverse events and 2 types of expected
      adverse events (tympanic membrane perforation, nausea after injection). No
      increases in dizziness or tinnitus lasting longer than 24 hours were observed
      after injections. One of 20 (5%) improved to near-normal hearing. In addition,
      there was statistically significant improvement in 4-frequency pure-tone average
      and speech discrimination score at 1 month after treatment. CONCLUSION: Four
      intratympanic injections of methylprednisolone improved pure-tone average or
      speech discrimination scores for a subset of sudden hearing loss subjects that
      failed to benefit from oral steroids. SIGNIFICANCE: A clinical trial of
      intratympanic injections for idiopathic sudden hearing loss was successfully
      completed and promising results were found.

PMID- 16087025
TI  - Spectrum of middle and inner ear abnormalities in infants with congenital heart
      defects.
AB  - OBJECTIVE: To evaluate temporal bone histopathology in infants with congenital
      heart defects (CHD). STUDY DESIGN AND SETTING: A retrospective review of our
      temporal bone collection was conducted to identify temporal bones acquired from
      infants with CHD. Subjects were divided into nonsyndromic and syndromic CHD
      groups. The presence of temporal bone abnormalities and the incidence of
      abnormalities that may result in hearing impairment were determined. RESULTS:
      Thirty-eight temporal bones obtained from 16 infants with nonsyndromic CHD and 4
      with syndromic CHD were evaluated. Nonsyndromic CHD cases had abnormalities such
      as a mesenchymal remnant, malformed stapes, persistent stapedial artery, shallow
      round window, dehiscent facial nerve canal, short cochlea, strial basophilic
      deposits, deformity of the spiral ligament, bulging Reissner's membrane,
      hypoplastic lateral semicircular canal, and cupular deposits. Syndromic CHD cases
      had abnormalities including narrow round window niche, facial canal dehiscence,
      strial basophilic deposits and cysts, and outer hair cell loss. Middle and inner
      ear abnormalities that may impair hearing were observed in 6 subjects with
      nonsyndromic CHD and in 1 subject with syndromic CHD. CONCLUSIONS: A wide variety
      of temporal bone defects were documented in infants with CHD. Congenital middle
      and inner ear abnormalities should be anticipated in the hearing assessment and
      otologic surgery of infants with CHD.

PMID- 16087026
TI  - Standard anesthetic technique for middle ear surgical procedures: a comparison of
      desflurane and sevoflurane.
AB  - OBJECTIVE: This study was designed to compare desflurane and sevoflurane
      anesthesia for middle ear microsurgery. STUDY DESIGN: One hundred healthy adults
      undergoing middle ear surgery were assigned to receive either desflurane or
      sevoflurane as their anesthetic. Intraoperative hemodynamics and BIS numbers were
      recorded. Hemodynamics, pain, nausea/vomiting, discharge readiness, and other
      parameters were compared postoperatively and 24 hours later. RESULTS: No
      intraoperative differences were noted except in BIS scores which trended lower
      with desflurane. PACU blood pressures were higher after desflurane but pain
      scores, nausea/vomiting, rescue anti-emetics, recovery scores, and discharge
      times were similar. A significant difference was noted in anesthetic costs
      (desflurane > sevoflurane), and in patients with the lowest BIS scores associated
      with more nausea/vomiting. CONCLUSIONS: Both anesthetics may be used for ototic
      surgery but propofol anesthesia should still be considered in patients with a
      history of emetic sequelae. SIGNIFICANCE: Short-acting inhalational anesthetics
      produce excellent operating conditions and reduce costs for otologic surgery.

PMID- 16087027
TI  - Cochlear implant magnet displacement with minor head trauma.
AB  - OBJECTIVES: Manufacturers have introduced cochlear implants (CIs) with removable
      magnets to allow for magnetic resonance imaging after placement. The purpose of
      this study was to describe magnet displacement as a new CI complication and to
      suggest a possible treatment option to prevent its recurrence. STUDY DESIGN:
      Retrospective case series. METHODS: The records of 3 young males who experienced
      CI magnet dislodgement were reviewed and compared against records from the
      institutional implant database. RESULTS: Magnet displacement was observed only in
      young males (14% of male children) who received CI with removable magnets. This
      occurred 13-14 months after CI placement. Magnets were replaced under general
      anesthesia, and the scalp was bolstered with a dermal allograft. Recurrent magnet
      dislodgement was encountered in 1 patient, 6 months later. CONCLUSIONS: Magnet
      displacement may be a relatively common complication after minor head trauma in
      pediatric patients with certain CIs that have removable magnets.

PMID- 16087028
TI  - Diagnosis and management of lateral semicircular canal benign paroxysmal
      positional vertigo.
AB  - OBJECTIVE: Describe the diagnosis, treatment, and outcome of a group of 20
      patients with lateral semicircular canal benign paroxysmal positional vertigo
      (LSC-BPPV). STUDY DESIGN AND SETTING: Retrospective review of 20 patients with
      LSC-BPPV (10 with geotropic and 10 with apogeotropic nystagmus) presenting to a
      tertiary balance center. Diagnosis was confirmed with infrared nystagmography in
      Dix-Hallpike positioning tests and supine positional tests. Patients were treated
      with one or more particle repositioning maneuvers. RESULTS: Addition of supine
      positional nystagmus tests to Dix-Hallpike positioning testing improves
      sensitivity in the diagnosis of LSC-BPPV. Treatment outcomes in the apogeotropic
      LSC-BPPV group were poorer than the geotropic LSC-BPPV group. SIGNIFICANCE:
      Adding supine positional testing to routine vestibular diagnostic testing will
      increase the identification of LSC-BPPV. Apogeotropic LSC-BPPV is more
      challenging to treat.

PMID- 16087029
TI  - Dexamethasone inner ear perfusion by intratympanic injection in unilateral
      Meniere's disease: a two-year prospective, placebo-controlled, double-blind,
      randomized trial.
AB  - OBJECTIVE: To investigate the efficacy of dexamethasone inner ear perfusion by
      intratympanic injection in hearing loss, tinnitus, aural fullness, and vertigo in
      the treatment of unilateral Meniere's disease and compare it with the control
      group. STUDY DESIGN AND SETTING: A prospective, randomized, double-blind study
      with 2-year follow-up comparing changes secondary to dexamethasone inner ear
      perfusion versus placebo consisting of saline solution. PATIENTS: Twenty-two
      patients having definite Meniere's disease as outlined by the 1995 American
      Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and
      Equilibrium. All the patients were older than 18 years of age and were not
      receiving any other form of treatment with steroids for their Meniere's disease.
      METHOD: Five consecutive daily intratympanic injections of dexamethasone or
      placebo to the involved ear. RESULTS: In the dexamethasone group at 2-year follow
      up, complete control of vertigo (class A) was achieved in 9 of 11 patients (82%)
      and substantial control of vertigo (class B) in the remaining 2 patients (18%.)
      In the control group only 7 of 11 patients (64%) finished the 2-year follow-up
      because in the other 4 patients (36%) we had to give another treatment for the
      continuing vertigo and thus they were classified as failure (class F.) From the 7
      patients who have finished the follow-up of 2 years in the control group, 4
      patients (57%) achieved class A, 2 patients (29%) achieved class C, and 1 patient
      (14%) class F. CONCLUSIONS: Dexamethasone (4 mg/mL) inner ear perfusion in a
      group of patients with unilateral Meniere's disease (Shea's stage III) showed 82%
      of complete control of vertigo over placebo (57%). There was also a subjective
      improvement in tinnitus (48%), hearing loss (35%), and aural fullness (48%) in
      the dexamethasone group compared with 20%, 10%, and 20% respectively in the
      control group.

PMID- 16087030
TI  - Local anesthesia for middle ear surgery.
AB  - The adequacy of anesthesia and comfort during surgery was assessed for 100
      consecutive patients undergoing middle ear surgery using local anesthesia, both
      by the patients themselves and by the surgeon. The possibility of inducing an
      iatrogenic facial weakness was also evaluated. Both the surgeon and the majority
      of patients were pleased with the quality of anesthesia and little adverse
      effects occurred as a consequence of local anesthesia itself.

PMID- 16087031
TI  - Visual loss as the initial symptom of squamous cell carcinoma of the tongue.

PMID- 16087032
TI  - Iatrogenic Brown's syndrome during endoscopic sinus surgery with powered
      instruments.

PMID- 16087033
TI  - Endoscopic repair of a hypopharyngeal laceration in a professional sword
      swallower.

PMID- 16087034
TI  - Malignant chondroid syringoma of the face: a first reported case.

PMID- 16087035
TI  - Human papilloma virus papilloma masquerading as adenoid hypertrophy.

PMID- 16087036
TI  - Proteolysis of beta-trace Protein?

PMID- 16087038
TI  - [First case in the world of autoreplantation of a limb associated with oral
      administration of an immunosupressant agent (FK 506-Tacrolimus)].
AB  - This is the case of the replantation of the upper limb of a sixty year old woman.
      The nature of the traumatism is an avulsion of the upper limb, at the junction of
      the middle third and the lower third of the humerus, which has a very bad
      prognosis. The originality of this report is the administration of Tacrolimus
      (immunosuppressive molecule) in an autotransplant. Tracolimus stimulates the
      nerve growing back, as already demonstrated in the animal and the fetus. In this
      preliminary report, the use of Tacrolimus over one year showed exceptional
      results. Indeed, the autors noticed clinical signs of intrinsic reinervation of
      the hand in the territory of the ulnar and median nerve. This has been confirmed
      with the use of electromyography. This is, as far as we know, the first
      observation of such results with adults and when the level of amputation is
      located so high. The authors think that the use of Tacrolimus should be tested in
      numerous cases of nerve lesions with bad prognosis such as high ulnar nerve
      lesions, serious plexus suffering or even in spinal cord trauma.

PMID- 16087039
TI  - [Extensor digitorum brevis muscle flap: its help in coverage of distal foot
      defects. Report of six cases].
AB  - From January 1997 to march 2002, six extensor digitorum brevis muscle flaps have
      been used in four women and two men. Their ages were between five and 65-years
      old. The defects were localised in the hallux in three cases, the dorsum of foot
      in one case, the other toes in one case and the external border of foot in one
      case. The defects were secondary to burn retraction in four cases, secondary to
      trauma in one case and secondary to osteomyelitis in another case. All the flaps
      were elevated on the distal dorsalis pedis artery with a retrograde flow. With an
      average of four years follow-up, all defects covered were very satisfying and
      there is no functional sequellae.

PMID- 16087040
TI  - [The palmar nail syndrome. Case report].
AB  - The congenital ectopic nail is very rare and usually present as an ectopic
      abnormal nail alongside the normal fingernail. Ridder described in 1992 the
      "congenital palmar nail syndrome" sharing a palmar ectopic nail, a loss of
      flexion and a small distal phalanx on x-ray. We report a case of a congenital
      palmar nail syndrome of both little fingers on a boy 13 years old.

PMID- 16087041
TI  - [Complex polydactyly of the limbs: mirror foot. Report of two cases and review of
      literature].
AB  - Polydactyly is the most common congenital limb anomaly occurring both as an
      isolated defect or as part of a syndrome. However mirror foot is an exceptional
      abnormality (14 cases reported). The authors describe two sporadic cases of
      mirror foot. The first case presents a mirror polydactyly of the left foot, an
      hexadactyly of the right foot and a central polysyndactyly of both hands. The
      second case presents a mirror polydactyly of both feet. Mirror foot is a very
      rare defect. Both sporadic and familiar cases have been reported. This
      malformation can affect one or both feet. Some cases are associated with other
      congenital anomalies. The definition of mirror foot is warying according to the
      authors and the review of literature shows an important variability in the
      patterns of mirror polydactyly. Mirror duplication of hands and feet result of
      aberrant positioning of the zone of polarizing activity in relation to the apical
      ectodermal ridge during limb bud development. Different genes encoding limb
      pattern have been described.

PMID- 16087042
TI  - [Four-layer laryngotracheoplasty to repair an anterior tracheal wall defect
      induced by a Montgomery T-tube].
AB  - A 37-year old patient was referred in 2000 for reconstruction of the anterior
      tracheal wall eroded by a Montgomery T-tube. A four-layer laryngotracheoplasty
      was proposed to the patient. The endotracheal plane was reconstructed by a
      bilateral random pattern quadrangular skin hinge flap raised from both sides of
      the defect. The chondral plane was realized with conchal cartilage. This
      cartilage graft was covered with an inferiorly based sternocleidomastoid flap.
      The fourth layer was a mesh split-thickness skin graft. Satisfactory and lasting
      results were observed during a three-year follow-up. Few articles deal
      specifically with tracheal reconstruction after anterior wall erosion induced by
      a Montgomery-T tube. We found no mention of the described four-layer flap in the
      literature.

PMID- 16087044
TI  - A comparison of methods for alignment of NMR peaks in the context of cluster
      analysis.
AB  - This paper compares the performance of two recently developed algorithms and
      methods for peak alignment of first-order NMR data of complex biological samples.
      The NMR spectra of such samples exhibit variations in peak position and peak
      shape due to variations in the sample matrix and to instrumental instabilities.
      The first method comprises an alignment of spectral segments with linear
      interpolation and shift correction to accommodate correspondence between a target
      and a test spectrum by a beam search or genetic algorithm. The second method is
      based on peak picking and needle vector representation of the NMR data with
      subsequent breadth-first search to establish shift corrections between the target
      and the test spectrum. The two proposed peak alignment methods and their
      respective merits are discussed for a real metabonomics application. Both
      alignment methods have been shown to enhance the interpretability of the
      resulting multivariate models, thereby increasing the prospect of detecting and
      following the onset of subtle biological changes reflected in the NMR data.

PMID- 16087045
TI  - Multivariate analysis of nuclear magnetic resonance data--characterization of
      critical drug substance quality of gentamicin sulfate.
AB  - Fourteen gentamicin sulfate lots collected from international markets showed high
      quantities of impurities (approximately 30% of studied lots). 1H NMR spectroscopy
      as a primary analytical method was applied in order to validate the
      quantification results obtained from micellar electrokinetic chromatography
      method (MEKC). In this study, 1H NMR data of 46 gentamicin sulfate drug substance
      lots were used to classify the lots by means of principal component analysis
      (PCA) of 14 1H NMR-signals in the 5.0-6.0 ppm region. Three main groups could be
      classified: high purity (3 lots), average quality (28 lots) and low purity (14
      lots); one lot proved to be atypical. The 14 normalized signal heights in the 5.0
      6.0 ppm region are predictive for purity quality according to a partial least
      squares (PLS)-model with sum of all impurities as Y-variable (measured by MEKC).

PMID- 16087046
TI  - NMR assays for carbohydrate-based vaccines.
AB  - Antibodies against the cell surface carbohydrates of many microbial pathogens
      protect against infection. This was initially exploited by the development of
      purified polysaccharide vaccines, but glycoconjugate vaccines, in which the cell
      surface carbohydrate of a microbial pathogen is covalently attached to an
      appropriate carrier protein, are proving the most effective means to generate
      this protective immunity. Carbohydrate-based vaccines against Haemophilus
      influenzae Type b, Neisseria meningitidis, Streptococcus pneumoniae and
      Salmonella enterica serotype Typhi (S. Typhi) are already licensed, and many
      similar products are in various stages of development. For many of these
      vaccines, biological assays are not available or are inappropriate and NMR
      spectroscopy is proving a valuable tool for the characterisation and quality
      control of existing and novel products. This review highlights some of the areas
      in which NMR spectroscopy is currently used, and where further developments may
      be expected.

PMID- 16087047
TI  - Quantitative NMR in synthetic and combinatorial chemistry.
AB  - The applications of quantitative NMR to synthetic organic chemistry are reviewed
      with taking into account both the small libraries (100-150 compounds) and the
      single, well-characterized substance. The precision and accuracy which are
      obtained with state of the art instrumentation--both around 1%--rival with other
      classical tools of quantitative analytics, and qNMR does not require a specific
      method setup or a standard of the same substance. This characteristic makes it
      the method of choice in an environment where many different molecules are
      investigated and reliable quantification is required. NMR may effectively replace
      other standard characterization tools, such as CHNS analysis, or even complex,
      multi-determination results as commonly required for the assessment of absolute
      purity or strength of a substance, when no specific standard is available.
      Finally, because of the high precision and intrinsic accuracy, quantitative NMR
      appears the ideal reference method for the validation of other, more rapid,
      generic techniques for quantitative analysis.

PMID- 16087048
TI  - 1H, 13C, 15N NMR analysis of sildenafil base and citrate (Viagra) in solution,
      solid state and pharmaceutical dosage forms.
AB  - Sildenafil citrate (SC) (Viagra) and sildenafil base in pure form are easily and
      unequivocally characterized by multinuclear NMR spectroscopy. Analysis of
      chemical shifts indicates that: (i) N6-H forms intramolecular hydrogen bonds,
      (ii) N25 is protonated in the salt and (iii) intermolecular OH...N hydrogen bonds
      involving N2 and N4 are present in the solid sildenafil citrate. 13C CPMAS NMR
      method has been proposed for the identification and quantitation of Viagra in its
      pharmaceutical formulations.

PMID- 16087049
TI  - Fluorine-19 or phosphorus-31 NMR spectroscopy: a suitable analytical technique
      for quantitative in vitro metabolic studies of fluorinated or phosphorylated
      drugs.
AB  - Fluorine-19 or phosphorus-31 NMR (19F NMR or 31P NMR) spectroscopy provides a
      highly specific tool for identification of fluorine- or phosphorus-containing
      drugs and their metabolites in biological media as well as a suitable analytical
      technique for their absolute quantification. This article focuses on the
      application of in vitro 19F or 31P NMR to the quantitative metabolic studies of
      some fluoropyrimidine or oxazaphosphorine drugs in clinical use. The first part
      presents an overview of the advantages (non-destructive and non-selective direct
      quantitative study of the biological matrices) and limitations (expensive cost of
      the spectrometers, limited mass or concentration sensitivity) of NMR
      spectroscopy. The second part deals with the criteria to be considered for
      successful quantification by NMR (uniform excitation over the entire spectral
      width of the spectrum, resonance signals properly characterised by taking into
      account T1 values and avoiding NOE enhancements, optimisation of the data
      processing, choice of a suitable standard reference). The third and fourth parts
      report some examples of quantification of 5-fluorouracil, its prodrug
      capecitabine, 5-fluorocytosine and their metabolites in bulk solutions
      (biofluids, tissue extracts, perfusates and culture media) and heterogeneous
      media (excised tissues and packed intact cells) as well as cyclophosphamide and
      ifosfamide in biofluids. These two parts emphasise the high potential of in vitro
      19F or 31P NMR for absolute quantification, in a single run, of all the fluorine-
      or phosphorus-containing species in the matrices analysed. The limit of
      quantification in bulk solutions is 1-3 microM for 19F NMR and approximately 10
      microM for 31P NMR. In heterogeneous media analysed with 19F NMR, it is 2-5 nmol
      in excised tissues and cell pellets.

PMID- 16087050
TI  - Microcoil nuclear magnetic resonance spectroscopy.
AB  - In comparison with most analytical chemistry techniques, nuclear magnetic
      resonance has an intrinsically low sensitivity, and many potential applications
      are therefore precluded by the limited available quantity of certain types of
      sample. In recent years, there has been a trend, both commercial and academic,
      towards miniaturization of the receiver coil in order to increase the mass
      sensitivity of NMR measurements. These small coils have also proved very useful
      in coupling NMR detection with commonly used microseparation techniques. A
      further development enabled by small detectors is parallel data acquisition from
      many samples simultaneously, made possible by incorporating multiple receiver
      coils into a single NMR probehead. This review article summarizes recent
      developments and applications of "microcoil" NMR spectroscopy.

PMID- 16087051
TI  - Hyphenation of capillary high-performance liquid chromatography to microcoil
      magnetic resonance spectroscopy--determination of various carotenoids in a small
      sized spinach sample.
AB  - The development of miniaturized hyphenated systems such as capillary high
      performance liquid chromatography--and nuclear magnetic resonance spectroscopy
      (HPLC-NMR) remains challenging in the field of structure elucidation. In
      combination with a highly specific sample preparation technique, matrix solid
      phase dispersion (MSPD), and a highly selective C30 reverse phase HPLC-NMR
      enables the identification of small amounts of natural compounds. Here, the
      investigation of five carotenoids in a standard solution and two carotenoids from
      a spinach sample demonstrate the potential of this new development. The
      separation of the carotenoids is performed with self-packed fused-silica
      capillaries with a binary solvent gradient consisting of acetone and water. The
      miniaturized system allows the use of fully deuterated solvents for on-line HPLC
      NMR coupling. The 1H NMR spectra of the various carotenoids obtained in stopped
      flow mode gave a high signal-to-noise ratio with a sample amount in the low
      nanogram range. All necessary parameters for structure elucidation such as
      multiplet structure, coupling constants and integration values can be detected
      unambiguously.

PMID- 16087052
TI  - Migraine and recurrent epistaxis in children.
AB  - Recurrent epistaxis is a common pediatric problem with uncertain etiology in most
      cases. We observed frequent complaints, or history of epistaxis in children with
      migraine. The aim of this study was to determine whether there is an association
      between epistaxis and migraine in children. A detailed questionnaire was used to
      conduct a study of 45 consecutive patients, ages 6-11 years, with migraine,
      diagnosed according to the 1997 proposed pediatric revisions to the International
      Headache Society criteria; the patients were evaluated in our Pediatric Neurology
      Clinic. Control subjects consisted of 64 children without recurrent headaches,
      matched as a group for age and sex, and drawn as a convenient sample from two
      general pediatric practices and an elementary school. Sixteen (36%) of 45
      patients with migraine had epistaxis as compared with 7 (11%) of 64 control
      subjects (odds ratio = 4.5; 95% confidence interval 1.6-12.1; P = 0.002).
      Epistaxis began an average of 3 years before migraine with similar
      characteristics to idiopathic epistaxis in habitual nose-bleeders, such as onset
      in early childhood, high incidence in sleep, and family history of epistaxis.
      This study demonstrates a significant association between migraine and recurrent
      epistaxis in children. Recurrent epistaxis increased the odds of migraine more
      than fourfold. Moreover, these data raise the question of whether epistaxis may
      represent a precursor to childhood migraine. The two disorders may share a common
      pathogenesis, and a prospective, longitudinal study is required to define further
      the relationship between them.

PMID- 16087053
TI  - Thiamine-responsive congenital lactic acidosis: clinical and biochemical studies.
AB  - We studied six infants with thiamine-responsive congenital lactic acidosis and
      normal pyruvate dehydrogenase complex activity in vitro, through clinical and
      biochemical analysis. In addition to elevated lactate and pyruvate levels, the
      data revealed increased urinary excretion of alpha-ketoglutarate, alpha
      ketoadipate, and branched chain ketoacids, indicating functional impairment of
      thiamine-requiring enzymes, such as pyruvate dehydrogenase complex, alpha
      ketoglutarate dehydrogenase complex, alpha-ketoadipate dehydrogenase, and
      branched chain amino acid dehydrogenase. The metabolism of thiamine has not been
      investigated in patients with thiamine-responsive congenital lactic acidosis. We
      evaluated two specific transport systems, THTR-1 (SLC19A2) and THTR-2 (SLC19A3),
      and a pyrophosphorylating enzyme of thiamine, thiamine pyrophosphokinase (hTPK
      1), in addition to pyruvate dehydrogenase complex and alpha-ketoglutarate
      dehydrogenase complex activity; no abnormality was found. Although the clinical
      features of thiamine-responsive congenital lactic acidosis are heterogeneous and
      clinical responses to thiamine administration vary, we emphasize the importance
      of early diagnosis and initiation of thiamine therapy before the occurrence of
      permanent brain damage. Careful monitoring of lactate and pyruvate would be
      useful in determining thiamine dosage.

PMID- 16087054
TI  - Cytokines involved in CNS manifestations caused by Mycoplasma pneumoniae.
AB  - Mycoplasma pneumoniae sometimes causes central nervous system manifestations,
      which may involve the host immune response, as the organism does not directly
      damage neural cells, or release toxins. Therefore we measured the levels of
      interleukin-6, interleukin-8, interleukin-18, interferon-gamma, tumor necrosis
      factor-alpha, and transforming growth factor-beta1 in serum and cerebrospinal
      fluid samples from patients who manifested central nervous system manifestations
      during acute M. pneumoniae infection. The subjects were nine patients with early
      onset encephalitis (central nervous system disease onset within 7 days from the
      onset of fever), four with late-onset encephalitis (onset at 8 days or later),
      three with encephalitis but without fever, and three with aseptic meningitis.
      Intrathecal elevations of interleukin-6 and interleukin-8 in all four types of
      central nervous system manifestations, and of interleukin-18 in late-onset
      encephalitis were observed. None of the cerebrospinal fluid samples contained
      detectable levels of interferon-gamma, tumor necrosis factor-alpha, or
      transforming growth factor-beta1. In conclusion, interleukin-6, interleukin-8,
      and interleukin-18 might be involved in the inflammatory process leading to the
      central nervous system manifestations caused by M. pneumoniae.

PMID- 16087055
TI  - Epilepsy and intrathecal baclofen therapy in children with cerebral palsy.
AB  - The objective of this study was to analyze the relationship between epilepsy and
      intrathecal baclofen by investigating a consecutive sample of 150 children with
      cerebral palsy or spasticity of cerebral origin who underwent intrathecal
      baclofen. The medical charts of the 150 children were retrospectively reviewed. A
      series of 100 children with cerebral palsy, operated on other procedures, was
      reviewed as a control group. Forty percent of the 150 children had epilepsy
      before intrathecal baclofen pump implantation; 13.3% had a decrease in seizure
      frequency after intrathecal baclofen, while two children worsened and one child
      had seizures ex novo. We conclude that in children with spasticity of cerebral
      origin, intrathecal baclofen does not seem to aggravate or induce seizure
      activity.

PMID- 16087056
TI  - ABCD1 gene mutations in Chinese patients with X-linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy is a neurodegenerative disorder caused by mutations
      in the adrenoleukodystrophy (ALD) protein gene ABCD1. This study used direct
      sequencing of genomic polymerase chain reaction products to perform mutational
      analysis of ABCD1 in 34 unrelated Chinese X-linked adrenoleukodystrophy patients
      and 27 of their maternal relatives. Thirty-two different mutations were
      identified in 34 patients. Most of the mutations (62.5%, 20/32) were missense
      mutations, six of which are novel. One novel single nucleotide polymorphism,
      c.1047 C>A, was also found in three patients and their mothers, which can also be
      observed in 1 of 120 normal control alleles. Two synonymous mutations (p.L516L
      and p.V349V) appeared in two unrelated patients, and no other mutations were
      evident after screening the gene's 10 exons. Seventeen of the probands' mothers
      were found to be heterozygous for the same mutations present in their sons' ABCD1
      gene. Eight of the 10 screened sisters and cousins were identified as carriers.
      There were no hot spot mutations in the ABCD1 gene of Chinese patients with X
      linked adrenoleukodystrophy. However, over half of the mutations (19/34) were
      located in exon 1 and exon 6, suggesting possible hot exons. No obvious
      relationship between genotype and phenotype was observed.

PMID- 16087057
TI  - Cerebrospinal fluid ACTH and cortisol in opsoclonus-myoclonus: effect of therapy.
AB  - Opsoclonus-myoclonus syndrome is one of a few corticotropin (ACTH)-responsive
      central nervous system disorders of childhood. We measured cerebrospinal fluid
      ACTH and cortisol in 69 children with opsoclonus-myoclonus and 25 age- and sex
      matched control subjects to determine endogenous levels and look for hypothesized
      differential hormonal effects of ACTH and corticosteroid treatment. Cerebrospinal
      fluid cortisol was 10-fold higher with ACTH treatment (n = 26), but was unchanged
      with oral steroid treatment (n = 18) or no treatment (n = 25). It was
      significantly higher in children receiving daily high-dose ACTH than alternate
      day ACTH. In ACTH-treated children, cerebrospinal fluid and serum cortisol were
      highly correlated (r = 0.96, P = 0.0001), with a mean ratio of cerebrospinal
      fluid to serum cortisol of approximately 1:10. Cerebrospinal fluid ACTH
      concentration did not differ significantly between untreated opsoclonus-myoclonus
      and control subjects but was lower with ACTH (-29%) or steroid treatment (-36%),
      suggesting feedback inhibition of ACTH release. These data delineate differences
      in the central effects of ACTH and corticosteroid therapy, as well as between
      high and low ACTH doses, and support the integrity of the brain-adrenal axis in
      pediatric opsoclonus-myoclonus.

PMID- 16087058
TI  - Incomplete alpha coma pattern in a child.
AB  - Only 19 cases of alpha coma pattern in the pediatric age group had been reported.
      Recently the concept of reactivity has been included in the definition of alpha
      coma. Electroencephalography reveals reactivity to painful stimuli in incomplete
      alpha coma. In adults, this pattern has a better prognosis than the complete
      pattern with no reactivity. A 5-year-old child had coma secondary to hypoxic
      brain damage after surgery. His electroencephalogram documented an incomplete
      alpha coma pattern. He remained in a vegetative state. This study is the first
      report of a child with incomplete alpha pattern documented on
      electroencephalogram.

PMID- 16087059
TI  - A case with quadriparetic cerebral palsy and cyanosis: congenital
      methemoglobinemia.
AB  - The recessive form of congenital methemoglobinemia, caused by a defect of
      nicotinamide adenine dinucleotide-cytb5 reductase enzyme (cytb5r), is a rare
      disorder clinically presenting with cyanosis. Two different forms of recessive
      congenital methemoglobinemia have been described: In type I, cyanosis is the only
      major symptom and enzyme deficiency is restricted to erythrocytes. In type II,
      observed in 10-15% of all patients, enzyme deficiency occurs in the entire body
      and cyanosis is associated with severe, progressive neurologic impairment. This
      report presents a 10-year-old female with recessive congenital methemoglobinemia
      type II. She was admitted with quadriparetic cerebral palsy, mental retardation,
      convulsions, swallowing difficulty, and cyanosis. Etiology of cyanosis was not
      clarified exactly but was readily but erroneously attributed to uncontrolled,
      repetitive convulsions and aspiration of excessive oral secretions. Her
      methemoglobin level was measured as 51%, and a diagnosis of congenital
      methemoglobinemia was established. Oral ascorbic acid 500 mg/day was initiated.
      She responded well to therapy. Interestingly, neurologic deficits improved after
      ascorbic acid treatment. In conclusion, cyanosis and repetitive convulsions
      associated with neurologic deficits may be explained by congenital
      methemoglobinemia, a potentially treatable condition.

PMID- 16087060
TI  - Idiopathic unilateral paralysis of the palate in childhood.
AB  - Idiopathic soft palate paralysis is an isolated clinical entity of unknown cause.
      Typical clinical features are sudden onset, rhinolalia, and nasal escape of
      fluids from the ipsilateral nostril. The disorder affects mainly male children at
      the ages of 2 to 3 years and resolves spontaneously. This report presents a 5
      year-old female with the rare disorder and discusses its probable
      physiopathologic mechanisms.

PMID- 16087061
TI  - Early onset of ataxia in a child with a pathogenic SCA8 allele.
AB  - This case report describes a child with an expanded CTA/CTG repeat in one allele
      of the spinocerebellar ataxia 8 gene. This patient presented with ataxia at a
      much earlier age than is typical for patients with this condition. This unique
      patient further highlights the complexity of the role that this molecular defect
      plays in the onset and course of the disease.

PMID- 16087062
TI  - Clinical and histologic changes in the follow-up of a congenital myopathy.
AB  - A 19-year-old woman was born with congenital hypotonia, generalized weakness, and
      dysmorphic features. A muscle biopsy performed at age 18 months found that type I
      fibers were smaller and more numerous than type II fibers, and she was diagnosed
      with congenital fiber type disproportion. She grew up with moderate motor
      impairment, but after a stationary period her weakness progressed gradually and
      she developed a severe ophthalmoplegia. When she was 18 years old a second muscle
      biopsy still indicated the predominance of type I fibers but also the presence of
      central nuclei and strong oxidative enzyme activity in the center of most of the
      fibers; this was compatible with centronuclear myopathy. The diagnostic
      reconsideration raises questions about the pathogenesis of these diseases and the
      recognition of congenital fiber type disproportion as a distinct nosologic
      entity.

PMID- 16087063
TI  - EEG evaluation of fixation-off sensitivity in eyelid myoclonia with absences.
AB  - A 14-year-old female of moderately retarded intelligence exhibited frequent
      seizures of eyelid myoclonia with absences. Video-electroencephalographic
      recording revealed that slow eye closure was followed by eyelid myoclonia with
      absence seizures and that paroxysmal burst activities in the occipital region
      always preceded generalized spike-wave discharges. Paroxysmal burst activities
      were induced not only by slow eye closure but also by fixation-off, wearing
      Frenzel glasses. We speculate that the sensitivity to fixation-off in the
      occipital lobe is one of the triggering mechanisms in eyelid myoclonia with
      absences.

PMID- 16087064
TI  - Familial arachnoid cysts.
AB  - Arachnoid cysts are a relatively common incidental finding on neuroimaging
      studies of the brain. Although most cases are sporadic, there have been some
      reports of arachnoid cysts in several members of the same family. This report
      describes two additional families with three members affected in each one. Both
      families had members with arachnoid cysts in two consecutive generations. In one
      of the families, arachnoid cysts were associated with a deletion in the long arm
      of chromosome 16, an association not described previously. These descriptions
      suggest that in some cases arachnoid cysts may have a genetic basis.

PMID- 16087066
TI  - Paralytic ileus in a MELAS patient mimicking MNGIE.

PMID- 16087067
TI  - Developmental and behavioral effects of acrylamide in Fischer 344 rats.
AB  - Human exposures to acrylamide (ACR), a known neurotoxicant, can occur via a
      variety of substances, including cigarette smoke and the ingestion of certain
      carbohydrate-based foods cooked at high temperatures. In this study, Fischer 344
      sperm plug-positive female rats were treated daily with ACR (0, 0.5, 1.0, 2.5,
      5.0 or 10.0 mg/kg/day) by gavage beginning on gestation day 7. Dosing of dams
      ended when litters were born; pups received daily gavage at the same dose as
      their dam from postnatal day (PND) 1 through PND22. Pups were tested using a
      battery of behavioral assessments from PNDs 4-22. Statistically significant
      decreases in body weight were observed in pups exposed to ACR at doses as low as
      1.0 mg/kg/day (treatmentxday; repeated measures ANOVA, P<0.0001). No
      statistically significant differences among treatment groups were observed in
      righting reflex, forelimb hang, or open field measures of activity. Statistically
      significant effects of ACR were observed at the 10 mg/kg/day dose on negative
      geotaxis performance (P<0.01) and a linear trend in fall-time latencies on
      Rotarod performance on PNDs 21-22 (P<0.05), with higher doses producing shorter
      latencies. These results suggest that ACR exposure produces deficits in
      development and motor coordination that are observable before weaning.

PMID- 16087068
TI  - Reappraisal of somatosensory disorders in methylmercury poisoning.
AB  - The first well-documented methylmercury (MeHg) poisoning by consumption of fish
      arose in Minamata, Japan in 1953. MeHg had dispersed from Minamata to the
      Shiranui Sea. The temporal changes in MeHg in the umbilical cords indicate that
      residents living around that Sea had been exposed to low-dose MeHg through fish
      consumption for about 20 years (at least from 1950 to 1968). They have complained
      of paresthesia at the distal parts of the extremities and around the lip even 30
      years after the cessation of exposure to anthropogenic MeHg. The thresholds of
      touch and two-point discrimination of those residents and Minamata disease (MD)
      patients were examined using the quantifiable instruments. They could perceive
      the stimulation of touch although their touch thresholds significantly increased
      in comparison to those of the control people. Their touch thresholds increased at
      the proximal extremities and the trunks as well as at the distal extremities. The
      evenly distributed increases at both distal and proximal parts revealed that the
      persistent somatosensory disturbances were not caused by the injuries to their
      peripheral nerves. The thresholds of two-point discrimination, which are
      associated with the function of the somatosensory cortex, increased at both
      forefingers and the lip in both groups. Taking into consideration that, the
      apraxia limb kinetics, astereognosis and disorder of active sensation, which are
      all associated with damage to the somatosensory cortex, were detected, it is
      proposed that the persisting somatosensory disorders after discontinuation of
      exposure to MeHg were induced by diffuse damage to the somatosensory cortex.

PMID- 16087069
TI  - Clinical applications of surface electromyography in neuromuscular disorders.
AB  - Surface electromyography (SEMG) is still rarely used in clinical settings for the
      detection and analysis of myoelectric signals. The electromyographic signal
      detected on the skin surface includes information from a greater proportion of
      the muscle of interest than conventional clinical EMG, acquired using needle
      electrodes. SEMG is therefore more representative than the localised, and thus
      very selective needle EMG signals currently used. However, both reliability and
      interpretation of surface EMG need to be questioned. This review looks at the
      studies concerned with the characterisation of neuromuscular pathologies using
      EMG parameters. After introducing principles and limitations of surface EMG, an
      overview of the main results obtained in clinical settings is presented and
      discussed. There is a particular focus on high spatial resolution surface EMG as
      it is currently the best compromise between the selectivity of needle EMG and the
      representative nature of classical SEMG. Several perspectives are proposed that
      underline the fact that surface EMG is an evolving discipline and should be
      worthy of a place in routine clinical examinations.

PMID- 16087070
TI  - Impaired corticolingual pathways in patients with or without dysarthria after
      acute monohemispheric stroke.
AB  - The occurrence of dysarthria is not infrequent in stroke but little is known
      about its pathophysiology. The aims of the present study were to assess the
      central motor innervation of the tongue in normal adults using transcranial
      magnetic stimulation (TMS) and to compare this with that seen in stroke patients
      with or without dysarthria. The study included 46 patients with acute
      monohemispheric stroke due to occlusion of the territory of the middle cerebral
      artery as documented by CT brain scan (26 patients with dysarthria and 20
      patients without dysarthria). Forty-five (age and sex matched) normal volunteers
      served as controls. Corticolingual pathways were assessed for each subject after
      TMS of each hemisphere. TMS over the motor cortex of healthy subjects elicited
      consistent ipsilateral and contralateral lingual responses. The ipsilateral
      response was usually smaller and approximately 73% of the amplitude of the
      contralateral response. The cross talk between the two halves of the tongue as
      estimated after unilateral electrical stimulation of hypoglossal nerve gave a
      contra/ipsi ratio of 36%, which was significantly smaller than the ratio seen
      after cortical stimulation (CL). For the patients, with or without dysarthria,
      motor evoked potential (MEP) latencies (ipsilateral and contralateral) were
      significantly prolonged after stimulation of affected hemisphere compared with
      the non-affected hemisphere or the control group (P< 0.001). MEP amplitudes were
      significantly smaller in hemiplegic patients with dysarthria compared to patients
      without dysarthria. In patients without dysarthria stimulation of the unaffected
      hemisphere tended to evoke responses that were of similar size on both sides.
      There were no significant associations between neurophysiological parameters and
      side of infarction. We conclude that interruption of the corticolingual pathways
      is frequent in stroke patients with or without dysarthria. The ability of
      unaffected hemisphere to evoke responses in the side contralateral to the lesion
      may relate to the absence or presence of dysarthria.

PMID- 16087071
TI  - Late event-related potentials and movement complexity in young adults with Down
      syndrome.
AB  - OBJECTIVES: Through event-related potential (ERP) recording, to better understand
      the perceptive-motor slowness in adults with Down syndrome (DS); in particular,
      to assess whether motor preparation influences the speed of allocation of
      perceptual attention as reflected by the P3 latency. PATIENTS AND METHODS: ERPs
      were obtained in adults with and without DS through an auditory oddball paradigm
      under a passive and two active (simple vs. complex motor response) conditions.
      Reaction times (RTs) were recorded in the two active conditions. RESULTS: There
      was no influence of movement complexity on either RT or P3b latency in the
      control group. In the DS group, RT was delayed under simple vs. complex
      conditions whereas P3b latency was not affected. N2a and N2b were often missing
      in DS individuals. CONCLUSION: Motor preparation processes per se rather than
      interaction with perceptual attention could be defective in individuals with DS
      when the motor component of the response is minimal.

PMID- 16087072
TI  - Laser evoked potentials and carbamazepine in epileptic patients.
AB  - AIMS OF THE STUDY: Nerve conduction studies have demonstrated that carbamazepine
      (CBZ), as well as other antiepileptic drugs (AEDs), can affect peripheral nerve
      conduction; reports on conventional somatosensory evoked potentials and CBZ are
      controversial. In a previous study, assessing laser-evoked potentials (LEPs) in
      CBZ-treated patients with idiopathic trigeminal neuralgia, we found that LEPs
      were dampened even after stimulation of the non-painful side, with a strong
      correlation between LEP latency and daily CBZ dose. No other study investigated
      the influence of AEDs on LEPs. In order to clarify the effect of CBZ on LEPs we
      sought possible LEP changes in epileptic patients taking CBZ. MATERIALS AND
      METHODS: We studied LEPs after trigeminal and hand CO(2)-laser stimulation in 20
      patients with epilepsy taking CBZ and 20 age-matched controls. RESULTS: Although
      the trigeminal LEP mean latency was slightly longer in epileptic patients
      (P=0.11), we did not find significant differences between epileptic patients and
      controls for any LEP data. LEP data did not correlate with the daily CBZ dose,
      CBZ blood concentration, or duration of therapy (P>0.3). CONCLUSION: The lack of
      a CBZ-induced dampening of LEPs suggests that small-fibre pathways, compared to
      large-fibre, might be less susceptible to AED's toxic effect. Although the TN
      patients in our previous study were older than the epileptic patients in the
      present study, a possible combined effect induced by drug and age in patients
      with TN is unlikely because LEP latency is reportedly unaffected by age. The CBZ
      induced effect in patients with trigeminal neuralgia is possibly related to
      pathophysiological changes specific to this disease.

PMID- 16087073
TI  - Automatic evaluation of the exteroceptive suppression of the temporalis muscle
      activity.
AB  - AIM: To set up a reliable automated method of allowing to identify the ES1 and
      ES2 periods of exteroceptive suppression of the temporal muscle (EST), thereby
      reducing their intra- and inter-individual variability. MATERIALS AND METHODS:
      Analyses were performed in 79 healthy subjects with strict inclusion and
      exclusion criteria. Each individual underwent two separate examinations 1 week
      apart. Activity of the left and right temporal muscles was recorded in response
      to unilateral stimulation of the left and right labial commissures. Wave forms
      were successively rectified, averaged, and filtered; the intersections of the
      resulting curve with values corresponding to 50%, 60%, 70%, 75%, and 80% of the
      control period (20 ms preanalysis time) were automatically determined. RESULTS:
      All subjects reached a 80% level of attenuation for ES2. The values of ES2
      durations were normally distributed. The mean ES1 and ES2 durations didn't vary
      between the two recording session, and there was a good individual
      reproducibility from one session to the other. Though relatively high, the inter
      individual variability was slightly lower in the second than in the first
      session. CONCLUSIONS: Computed analysis of EST may contribute to decrease inter-
      and intra-individual test variability. Letting patient habituate through a first
      recording session could increase test sensitivity, too. The obtained values for
      ES2 duration are normally distributed and well-reproducible at both the
      population and individual level. We suggest taking into account both ES2 duration
      and level of attenuation.

PMID- 16087075
TI  - CT screening for lung cancer: past and ongoing studies.
AB  - It has been widely recognized that the oft-quoted randomized clinical trials
      (RCTs) of lung cancer screening by chest radiography--studies that were
      interpreted as showing no benefit--were seriously flawed. We begin by describing
      the shortcomings of these trials and presenting an analysis of the problems
      typically encountered in performing RCTs in this area. Screening for lung cancer
      using computed tomography (CT) has shown that CT offers great superiority over
      chest radiography in diagnosing small lung cancers in the three studies that
      performed both CT and chest radiography on all patients. The Early Lung Cancer
      Action Project (ELCAP), showed that false-positive results can be kept reasonably
      low and are much less common on repeat screening, and that CT screening can be
      managed with no notable excess of percutaneous or surgical biopsies when
      following a well-defined regimen of screening. This regimen details the
      parameters of the initial CT, the definition of a positive result, and the
      subsequent work-up of positive results. Following the updated International (I)
      ELCAP protocol, it has been further found that (1) the frequency of positive
      results is low: 15% for the baseline cycle of screening and 6% for the subsequent
      cycles. (2) The frequency of screen-diagnoses as compared with all diagnoses is
      97% or higher. (3) The relative frequency of presurgical Stage I is well over
      80%; the median diameter of the screen-diagnosed cases on repeat screening is 8
      mm (versus 15 mm at baseline screening). (4) A high percentage of the screen
      diagnosed cases were genuine cancers which led to death if not treated. (5) The
      estimated 8-year cure rate for resected baseline screen-diagnosed lung cancers
      without evidence of lymph node metastases is 95% and for resected annual repeat
      cancers is 98%. (6) CT screening appears to be highly cost-effective. These
      preliminary results of CT screening suggests that the cure rate of screen
      diagnosed lung cancer, using the I-ELCAP regimen of screening, may be over 70% as
      compared with that of usual care of 10% and that of chest radiographic screening
      of 20%.

PMID- 16087076
TI  - Implication of the CT characteristics of subcentimeter pulmonary nodules.
AB  - Screening by low-dose helical computed tomography (CT) detects many small
      pulmonary nodules less than 1 cm in diameter. Pulmonary nodules can be
      practically classified into three types by their CT appearance: pure ground-glass
      opacity (GGO), GGO with a solid central component, and solid nodule. Ground-glass
      opacity on thin-section CT is considered to most commonly represent focal
      bronchoalveolar carcinoma. However, one-third of pure GGOs represent atypical
      adenomatous hyperplasia. Noguchi has classified small adenocarcinomas into
      pathological subtypes (A through F) that appear to have clinical significance.
      Noguchi types D-F can be differentiated from types A, B, and C by CT findings-
      however, CT does not appear to be able to reliably distinguish D-F lesions and
      squamous cell carcinoma from benign tumors. The rate of obtaining a correct
      preoperative diagnosis on the basis of CT findings was significantly elevated
      after we instituted a program of preoperative evaluation based on defined thin
      section CT characteristics of small nodules. Although emerging data suggest that
      limited resection for malignant lesions 10 mm or less may be appropriate,
      particularly for Noguchi types A-C, this remains controversial.

PMID- 16087077
TI  - Is there a role for PET in the evaluation of subcentimeter pulmonary nodules?
AB  - There are little published data available at this time to determine the
      appropriate role of positron emission tomography (PET) in the evaluation of
      subcentimeter pulmonary nodules. The sensitivity for malignancy is lower in these
      smaller lesions, while one would expect the specificity to be higher. Given that
      the resolution of current generation PET scanners is only 5 to 6 mm, one will be
      very unlikely to gain useful information from PET for a lesion below 5 mm. For
      lesions 5 to 10 mm in size, useful information might be gained from PET in those
      deemed intermediate risk by CT criteria, but this remains to be established. A
      positive PET in a small, intermediate risk lesion might push one toward
      biopsy/excision, though a negative PET in such a lesion must be considered to
      provide no information whatsoever. Even with advances in PET technologies in the
      future, we feel it is unlikely that PET will evolve a major role in the
      evaluation of the subcentimeter nodule.

PMID- 16087078
TI  - A proposed diagnostic approach to the patient with the subcentimeter pulmonary
      nodule: techniques that facilitate video-assisted thoracic surgery excision.
AB  - This article describes a diagnostic approach to the management of subcentimeter
      pulmonary nodules and delineates the contribution the chest surgeon brings to
      clinical decision making. This includes clinical experience and knowledge of
      nodule accessibility to thoracoscopic excisional biopsy based on the anticipated
      localization technique to be used. Characteristics of the ideal localization
      technique are discussed. Different localization techniques are then described,
      and their respective advantages and disadvantages are discussed. These techniques
      include intraoperative finger and instrument localization, preoperative
      radiologically placed hooks and coils, intraoperative ultrasonography, and
      preoperative placement of radiotracer markers.

PMID- 16087079
TI  - Bronchioloalveolar carcinoma in small pulmonary nodules: clinical relevance.
AB  - Increased use of chest computed tomography (CT) as well as improvements in CT
      resolution has led to increased detection of subcentimeter pulmonary nodules.
      Although the majority of these nodules are benign in etiology, a subset will
      harbor bronchioloalveolar carcinoma. The diagnosis of malignancy in this setting
      can be challenging to radiologists, surgeons, and occasionally pathologists as
      well. The challenge is compounded by a lack of knowledge about the natural course
      of these lesions--specifically, whether they represent life-threatening
      aggressive malignancies or indolent lesions of little or no consequence. Given
      the relative infrequency of these abnormalities, it will be essential to
      establish a sufficiently large database, to organize multi-institutional
      registries, and to collaborate on correlative studies. Only in this way will we
      be able to determine the clinical and molecular characteristics of these lesions
      and thus hopefully gain insight into their clinical relevance.

PMID- 16087080
TI  - Sublobar resection for the subcentimeter pulmonary nodule.
AB  - Several studies have demonstrated an increased local recurrence rate with
      sublobar resection (SR) when compared with lobar resection for the treatment of
      non-small-cell lung cancer (NSCLC). Therefore, lobectomy has remained the gold
      standard therapy for NSCLC with lesser resection reserved as a compromise
      operation for high-risk patients. The increased identification of small NSCLC
      tumors by CT scan is leading many surgeons to question the appropriateness of
      lobectomy for these tumors. There has been increasing interest by many surgeons
      to use SR as intentional therapy for patients with small peripheral NSCLC. This
      article reviews the recent literature and evidence supporting intentional SR for
      NSCLC. Although lobectomy should continue to be regarded as the procedure of
      choice for NSCLC, we believe that a subset of patients with favorable
      characteristics may be appropriately treated with intentional SR as long as good
      assessment of nodal involvement is made. Future investigation is required to
      better define when SR is appropriate.

PMID- 16087081
TI  - Radiofrequency ablation: emerging therapy for the small pulmonary nodule?
AB  - Traditional approaches to small pulmonary nodules have ranged from serial
      radiographic surveillance to transthoracic needle aspiration to surgical
      resection for diagnosis. Once the diagnosis of non-small-cell lung cancer is
      secured, lobectomy remains the gold standard treatment. Nevertheless, advances in
      image-guided technology and radiofrequency thermal ablation techniques have
      allowed for diagnostic sampling of lesions with concomitant therapeutic thermal
      ablation. The role these techniques will play in the treatment of patients with
      primary lung cancer remains undefined. This review (1) examines the basic
      technology of radiofrequency ablation; (2) provides an update on current clinical
      experience with this technique; and (3) explores the role of radiofrequency
      ablation in the treatment scheme of patients with non-small-cell lung cancer.

PMID- 16087083
TI  - Treatment of coarctation and late complications in the adult.
AB  - This article discusses coarctation of the aorta in the adult. Effective
      treatments for coarctation have come from surgery since 1945 and from
      interventional cardiology since 1982. Long-term outcome data are available only
      for surgical approaches. Thirty-year survival rate is 72% to 82%. Complications
      include recoarctation or residual coarctation, hypertension, aneurysms at the
      repair site, spinal cord injury. Other sequelae include bicuspid aortic valve
      disease, ascending aortic aneurysm, premature coronary disease, and infective
      endocarditis or endarteritis. Interventional catheter therapy is now the
      preferred therapy for recurrent coarctation, when the anatomy permits and
      necessary skills are available. Its use in native or unoperated coarctation is
      less well established. Treatment may be with balloon angioplasty alone or with a
      stent. Outcomes are good in skilled hands, but residual or recurrent coarctation
      with resultant hypertension and repair site aneurysms can occur. Catheter
      treatment can cause death from aortic rupture and dissection, but mortality
      compares favorably with surgery if coarctation is recurrent, and perhaps for
      initial treatment.

PMID- 16087084
TI  - Management of the valve and ascending aorta in adults with bicuspid aortic valve
      disease.
AB  - Bicuspid aortic valve (BAV) disease is the most common congenital cardiac
      malformation, being present in 1% to 2% of the population. It is heritable and is
      three to four times more likely to occur in men. The pathogenesis of BAV disease
      is unknown. Bicuspid valves progress to aortic stenosis or insufficiency in the
      majority of patients. BAV disease is associated with several anomalies of the
      aorta including coarctation, aneurysm formation, and dissection. Several lines of
      evidence suggest that aortic complications are caused by the same underlying
      factor that causes BAV disease, rather than being a consequence of turbulent
      blood flow through a stenotic valve. Several different surgical options exist for
      patients with BAV disease depending on the age of presentation and the size and
      appearance of the aorta. We herein describe our surgical management of the aortic
      valve and ascending aorta in patients with BAV disease.

PMID- 16087085
TI  - Surgical management of Ebstein's anomaly in the adult.
AB  - Ebstein's anomaly is a rare cardiac malformation that affects the tricuspid
      valve, right ventricle, and right atrioventricular junction. These anatomical and
      functional abnormalities cause important tricuspid regurgitation that results in
      right atrial and right ventricular dilatation and atrial and ventricular
      arrhythmias. Diagnosis is made by echocardiography. Operation includes tricuspid
      valve repair or replacement, closure of any interatrial communications, and
      appropriate antiarrhythmia procedures. Repair of Ebstein's anomaly eliminates
      right-to-left intracardiac shunting, improves exercise tolerance and functional
      class, and reduces supraventricular arrhythmias. In addition, quality of life and
      longevity are improved.

PMID- 16087086
TI  - Late complications of repair of tetralogy of Fallot and indications for pulmonary
      valve replacement.
AB  - With increasing follow-up of patients after surgical repair of tetralogy of
      Fallot, the long-term complications of chronic pulmonary regurgitation (PR),
      ventricular dilation, electrical inhomogeneity and myocardial scarring are
      becoming apparent. In this article we review the existing literature regarding
      the deleterious effects of chronic PR in these patients and the current data
      regarding the timing and mode of intervention.

PMID- 16087087
TI  - Management of the failing systemic right ventricle.
AB  - Conditions in which the right ventricle serves as the systemic pumping chamber
      are frequently complicated by the development of right ventricular failure and
      tricuspid valve regurgitation. The right ventricle is the systemic ventricle in
      conditions of ventriculoarterial discordance with atrioventricular concordance
      (transposition of the great arteries) or with atrioventricular discordance
      (congenitally corrected transposition of the great arteries). Concerns regarding
      actual or potential systemic right ventricular failure in these cases may lead to
      surgical evaluation and treatment designed to reestablish the left ventricle as
      the systemic pump. In cases where the left ventricle has prolonged exposure to
      low pressures in the pulmonary circulation, the left ventricle must be
      "retrained" to assume a systemic pressure load. Anatomic repair, with or without
      a preparatory period of left ventricular retraining, is a consideration for three
      clinically relevant scenarios: (1) patients with transposition of the great
      arteries after an atrial level switch (Senning or Mustard procedure), (2)
      patients with congenitally corrected transposition who are unoperated or who have
      undergone physiologic ("classic") repair, and (3) unoperated patients with
      transposition who present after the neonatal period.

PMID- 16087088
TI  - Extracardiac Fontan conversion, cryoablation, and pacemaker placement for
      patients with a failed Fontan.
AB  - OBJECTIVE: We review our experience with Fontan conversion and cryoablation in
      patients with an atriopulmonary Fontan in low cardiac output from arrhythmia or
      venous obstruction, including two patients with protein losing enteropathy.
      METHODS: Fifteen patients (mean age 25.0 +/- 8.4 years) underwent extracardiac
      Fontan conversion, cryoablation, and pacemaker placement between November 1999
      and December 2004. Twelve patients were in NYHA class III and three were in NYHA
      class IV. Twelve had clinically important intraatrial reentry tachycardia
      refractory to medical therapy. RESULTS: Follow-up was between 2 and 62 months
      (mean 38.4 +/- 17.7). One death occurred at seven days after surgery due to
      sepsis and multisystem organ failure. The second death occurred at five days from
      myocardial depression following surgery. One patient with PLE preoperatively died
      to malnutrition and sepsis on POD number 52. The second patient with protein
      losing enteropathy had improved NYHA classification, cessation of albumin
      transfusions, and a normal stool alpha antitrypsin level (down from 4.1 mg/g
      preoperatively). All surviving patients improved NYHA classification to class I
      or II. Sustained arrhythmias could not be induced in any patient. One patient had
      recurrence of intraatrial reentrant tachycardia eleven months postoperatively
      that required electrical cardioversion and is currently well controlled on one
      medication. The other patients are not on any antiarrhythmic medical therapy.
      CONCLUSION: Extracardiac Fontan, cryoablation, and pacemaker placement reduced
      atrial arrhythmias and improved NYHA classification. In selected patients, this
      operation offers improvement in clinical outcome and is an alternative to
      transplantation. Protein losing enteropathy may not be a contraindication to
      performing Fontan conversion with cryoablation.

PMID- 16087089
TI  - Optical scanning and breast cancer.

PMID- 16087090
TI  - Interobserver and intraobserver variability in the assessment of pulmonary nodule
      size on CT using film and computer display methods.
AB  - RATIONALE AND OBJECTIVES: A critical element in determining biologic behavior of
      pulmonary nodules is volume and temporal volume change. We evaluate variability
      in nodule volume among readers and measuring methods. MATERIALS AND METHODS: 55
      small (<2 cm) lung nodules were measured in long- and short-axis dimensions
      independently by 4 radiologists, using 3 methods: 1) hard copy, 2) GE Advantage
      Windows workstation (GE Healthcare, Milwaukee, WI), 3) Siemens IMACS workstation
      (Siemens Medical Systems, Iselan, NJ). Nodule margin was recorded as smooth,
      lobulated, or spiculated. Volume was calculated from diameter measurements.
      Variability in nodule volume was evaluated within each reader, between readers,
      and across measurement tools. RESULTS: Mean nodule short-axis diameter was 5.3
      mm; mean long-axis diameter 7.2 mm. There was statistically significant variation
      among readers and measurement method for nodule volume. Volume was significantly
      larger using hard-copy measurements (51.9%-54.1% variation; P < .0001) than
      either workstation, and not different between workstations. There was greater
      intraobserver variability in volume using the hard-copy method, and no difference
      between workstation methods. Volumes based on measurements from one reader were
      consistently lower than those from other readers (P = < .001, .003, and .02);
      volume was consistently larger for another reader (P < .0001, .03, and .12).
      Reader agreement for nodule margin was good to excellent. CONCLUSION:
      Considerable interobserver and intraobserver variability in measuring nodules
      exists using hard-copy and computer tools. Since a small change in diameter
      indicates a much larger change in volume, this may be significant when using
      early repeat CT to follow small pulmonary nodules. Computer-aided diagnostic
      tools that reproducibly measure nodule volume are strongly needed.

PMID- 16087091
TI  - Multimodality computerized diagnosis of breast lesions using mammography and
      sonography.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study is to investigate the use of
      computer-extracted features of lesions imaged by means of two modalities,
      mammography and breast ultrasound, in the computerized classification of breast
      lesions. MATERIAL AND METHODS: We performed computerized analysis on a database
      of 97 patients with a total of 100 lesions (40 malignant, 40 benign solid, and 20
      cystic lesions). Mammograms and ultrasound images were available for these breast
      lesions. There was an average of three mammographic images and two ultrasound
      images per lesion. Based on seed points indicated by a radiologist, the computer
      automatically segmented lesions from the parenchymal background and automatically
      extracted a set of characteristic features for each lesion. For each feature, its
      value averaged over all images pertaining to a given lesion was input to a
      Bayesian neural network for classification. We also investigated different
      approaches to combine image-based features into this by-lesion analysis. In that
      analysis, mean, maximum, and minimum feature values were considered for all
      images representing a lesion. We considered performance by using a leave-one
      lesion-out approach, based on image features from mammography alone (two to five
      features), ultrasound alone (three to four features), and a combination of
      features from both modalities (three to five features total). RESULTS: For the
      classification task of distinguishing cancer from other abnormalities in a lesion
      based analysis by using a single modality, areas under the receiver operating
      characteristic curves (A(z) values) increased significantly when the computer
      selected the manner (mean, minimum, or maximum) in which image-based features
      were combined into lesion-based features. The highest performance was found for
      lesion-based analysis and automated feature selection from mean, maximum, and
      minimum values of features from both modalities (resulting in a total of four
      features being used). That A(z) value for the task of distinguishing cancer was
      0.92, showing a statistically significant increase over that achieved with
      features from either mammography or ultrasound alone. CONCLUSION: Computerized
      classification of cancer significantly improved when lesion features from both
      modalities were combined. Classification performance depended on specific methods
      for combining features from multiple images per lesion. These results are
      encouraging and warrant further exploration of computerized methods for
      multimodality imaging.

PMID- 16087092
TI  - Management of patients with "ex vacuo" pneumothorax after thoracentesis.
AB  - RATIONALE AND OBJECTIVES: To determine clinical outcome in patients who developed
      "ex vacuo" pneumothorax following thoracentesis and to assess the benefit of
      chest tube placement for this complication. MATERIALS AND METHODS: We
      retrospectively reviewed records of 282 patients who underwent 437 thoracenteses
      at a single institution during a 6-year period. We identified 34 patients (12.1%)
      who developed a pneumothorax following 39 thoracenteses (8.8%) and then
      identified a subset of patients with pneumothorax "ex vacuo" defined as a
      moderate to large hydropneumothorax or small pneumothorax persisting for more
      than 3 days. Patient charts were reviewed to document the treatment strategy
      employed and subsequent clinical outcome, which included length of hospital stay,
      resolution of pneumothorax, reaccumulation of pleural effusion, and overall
      survival. RESULTS: Ten patients developed "ex vacuo" pneumothroax following
      thoracentesis. None complained of significant worsening of symptoms following
      thoracentesis. Seven patients were treated by observation alone and 3 patients
      underwent tube thorocostomy. A decrease in size of the pneumothorax was observed
      in only 3 patients, none of whom had a chest tube placed. Effusion completely
      reaccumulated in 7 patients. All 10 patients died during the follow-up period;
      the mean survival was 157 days (range: 13-402 days). Survival among patients
      treated by observation was 191.4 days versus 71.7 days for patients receiving
      chest tubes. CONCLUSION: Life expectancy for most patients who develop "ex vacuo"
      pneumothorax following therapeutic thoracentesis is short (<6 months). Chest tube
      placement is not necessary in asymptomatic patients and is unlikely to provide
      clinical benefit.

PMID- 16087093
TI  - Accuracy of computed tomography attenuation values in the characterization of
      pleural fluid: an ROC study.
AB  - RATIONALE AND OBJECTIVES: To assess the accuracy of computed tomography (CT) in
      characterizing pleural fluid based on attenuation values. MATERIALS AND METHODS:
      Protocol was approved by the local institutional review board and informed
      consent was waived. We retrospectively analyzed 145 pleural effusions of 145
      patients (mean/standard deviation age: 60.7/15.9 years; 69 females) who underwent
      CT of the thorax and diagnostic thoracentesis within 7 days of each other.
      Effusions were classified as transudates or exudates using laboratory markers
      based on Light's criteria. The mean Hounsfield units (HU) of an effusion was
      determined by a region of interest on the three slices with the greatest
      anteroposterior diameter. A receiver operating characteristic curve was
      constructed to determine threshold values for classification on the basis of mean
      HU and to examine overall accuracy, using the area under the curve (A(z)).
      RESULTS: Of the 101 exudates and 44 transudates, the mean attenuation of exudates
      (17.1 HU/standard deviation 4.4) was significantly higher than transudates (12.5
      HU/6.3), (P < .001). There was a modest but significant positive relationship
      between mean HU and laboratory markers, with the strongest relationship with
      pleural/serum protein (r = 0.57, P < .001) and total pleural protein (r = 0.56, P
      < .001). The overall accuracy of attenuation values for identifying exudates was
      moderate, Az = 0.775, standard error = 0.039, with the largest limitation being
      the overlap with transudates in the 10-20 HU range, which constituted 66%
      (90/145) of the total effusions measured. CONCLUSION: Although the mean
      attenuation of exudates is significantly higher than transudates, the clinical
      use of CT numbers to characterize pleural fluid is not recommended, as their
      accuracy is only moderate. Moreover, there is a notable overlap in attenuation
      values between transudates and exudates for a majority of effusions.

PMID- 16087094
TI  - Intravertebral cleft sign on fat-suppressed contrast-enhanced MR: correlation
      with cement distribution pattern on percutaneous vertebroplasty.
AB  - RATIONALE AND OBJECTIVES: Filling intravertebral clefts during percutaneous
      vertebroplasty (PVP) is considered to be important for optimal pain control. It
      is often difficult to detect clefts on non-contrast MR and some fractures show a
      solid pattern distribution of injected cement without a cleft sign on non
      contrast MR. In this study, we evaluated usefulness of fat-suppressed contrast
      enhanced MR to predict a solid pattern distribution of injected cement on PVP.
      MATERIALS AND METHODS: Twenty-six patients with 35 vertebral compression
      fractures due to osteoporosis were studied. We performed sagittal T1-weighted, T2
      weighted and fat-suppressed contrast-enhanced T1-weighted images prior to PVP.
      First we evaluated the presence of fluid-filled or gas-containing clefts on non
      contrast MR. Next we evaluated contrast-enhanced MR of the same vertebrae for the
      presence of cleft-shaped unenhanced areas within the diffuse enhancement area. We
      correlated MR findings with cement distribution patterns of injected cement.
      RESULTS: Based on MR findings, 35 osteoporotic fractures were divided into 3
      types. Type 1 (11 fractures, 31%): There were no clefts on non-contrast MR and no
      unenhanced areas on contrast-enhanced MR; Type 2 (13, 37%): There were no clefts
      on non-contrast MR but there were unenhanced areas on contrast-enhanced MR; Type
      3 (13, 37%): There were clefts on non-contrast MR and unenhanced areas on
      contrast-enhanced MR. Of 35 osteoporotic fractures, thirteen vertebral fractures
      (37%) were noted to contain clefts on non-contrast MR, while 24 vertebral
      fractures (69%) contained unenhanced areas on contrast-enhanced MR. Cement
      distributed as a solid pattern within clefts or unenhanced areas in all fractures
      with them. CONCLUSION: Fat-suppressed contrast-enhanced MR is useful to predict a
      solid pattern distribution of injected cement prior to PVP.

PMID- 16087095
TI  - Enterprise-wide PACS: beyond radiology, an architecture to manage all medical
      images.
AB  - RATIONALE AND OBJECTIVES: Picture archiving and communication systems (PACS) have
      the vocation to manage all medical images acquired within the hospital. To
      address the various situations encountered in the imaging specialties, the
      traditional architecture used for the radiology department has to evolve.
      MATERIALS AND METHODS: We present our preliminarily results toward an enterprise
      wide PACS intended to support all kind of image production in medicine, from
      biomolecular images to whole-body pictures. Our solution is based on an existing
      radiologic PACS system from which images are distributed through an electronic
      patient record to all care facilities. This platform is enriched with a flexible
      integration framework supporting digital image communication in medicine (DICOM)
      and DICOM-XML formats. In addition, a generic workflow engine highly customizable
      is used to drive work processes. RESULTS: Echocardiology; hematology; ear, nose,
      and throat; and dermatology, including wounds, follow-up is the first implemented
      extensions outside of radiology. CONCLUSION: We also propose a global strategy
      for further developments based on three possible architectures for an enterprise
      wide PACS.

PMID- 16087096
TI  - Projection extension for region of interest imaging in cone-beam CT.
AB  - RATIONALE AND OBJECTIVES: For 3D X-ray imaging during interventions, changes of
      the imaged object are often restricted to a small part of the field of view,
      suggesting region of interest (ROI) imaging by irradiating this area only. In
      this article, we present a novel method for extension of truncated projections in
      order to avoid truncation artifacts in C-arm based 3D ROI imaging. MATERIALS AND
      METHODS: The method makes use of prior knowledge by combining forward projections
      of a previously acquired, nontruncated 3D reference image with the truncated ROI
      projections. Rigid registration between the two datasets is achieved by using a
      technique based on local cross-correlation. To account for a gray value mismatch
      between the two data sets due to, e.g., differing beam quality and different
      contributions of scattered radiation, a linear gray level transformation is
      applied to the forward-projected reference data. RESULTS: The performance of
      different gray value transformation schemes is systematically assessed by means
      of numerical simulations. For various simulated scenarios, the best performing
      transformation has been identified, providing practical guidelines for selecting
      a scheme depending on the origin of the gray-level mismatch. Experiments prove
      the high performance of the developed method. CONCLUSION: The presented technique
      enables almost artifact-free 3D ROI imaging during interventions. This actually
      allows for repeated scans at low dose and enables intraprocedural imaging of
      large objects even with a small detector. However, applicability of the method is
      limited to scenarios where direct access to a reference image, e.g., a prior CT
      scan, is available.

PMID- 16087097
TI  - CAD-aided mammogram training.
AB  - RATIONALE AND OBJECTIVES: Although computer-aided detection (CAD) improves the
      diagnosis rate of early breast cancer, it has not been well integrated into
      radiology residency and technician training program. Moreover, CAD performance
      studies ignore the reader's training and experience with CAD. The purpose of this
      study was to investigate whether CAD training via a cognitive-perceptual based
      hypermedia program has effects on the performance studies of mammogram reading.
      MATERIALS AND METHODS: Three observers read a pretest set of 80 breast cancer
      cases (43 negative, 23 benign, and 14 malignant cancer cases). During 4 weeks'
      training, the observers used a hypermedia instructional program in CAD-aided
      mammography interpretation. The program includes modules of CAD attention
      focusing schemes, CAD procedural knowledge, and case-based simulations in
      mammography interpretation in consensus with CAD. By the end of the fourth week
      of the training, they reviewed a posttest set of cases. Data were analyzed with
      multireader, multicase receiver operating characteristic methods. RESULTS: Three
      readers performed better in mammogram reading after training in CAD knowledge
      than they did before CAD training. CAD training and experience improved the
      performance of CAD-aided mammography interpretation. CONCLUSION: A statistically
      significant difference was found in each observer's performance in CAD-aided
      mammogram reading before and after the training. CAD training will influence the
      perception, recognition, and interpretation of early breast cancer and CAD
      performance studies. Furthermore, the young generation of radiologic
      professionals can have more training in various attention-focusing features,
      declarative knowledge, procedural knowledge, and conditional knowledge of CAD and
      incorporate them into their knowledge base and strategic processing for the
      purpose of improving the accuracy of mammography interpretation performance.

PMID- 16087098
TI  - Toward atlas-assisted automatic interpretation of MRI morphological brain scans
      in the presence of tumor.
AB  - RATIONALE AND OBJECTIVES: Determination of distorted brain anatomy surrounding a
      tumor causing a mass effect is much more difficult than interpretation of normal
      brain scans, particularly because this distortion is not easily predictable a
      tumor may be located in any place and vary substantially in size, shape, and
      radiological appearance. The objective of our work is to provide a qualitative
      means for rapid estimation of brain anatomy distorted by tumor. MATERIALS AND
      METHODS: Toward achieving this objective, we use an electronic and deformable
      brain atlas of gross anatomy along with a fast atlas-to-data warping technique.
      The deformed atlas determines the distorted anatomy surrounding a tumor and can
      be used for structure labeling (naming). The warping algorithm uses the Talairach
      transformation followed by three-dimensional nonlinear tumor deformation based on
      a geometric assumption that the tumor, delineated on radiological images,
      compresses its surrounding tissues radially. RESULTS: The approach is implemented
      and a dedicated application is developed. It processes the data automatically in
      five steps: (1) load data, (2) set the Talairach landmarks and perform the
      Talairach transformation, (3) segment the tumor, (4) warp the scan nonlinearly in
      three dimensions, and (5) explore the scan. The approach is very fast, and a
      magnetic resonance imaging scan is processed in 10-15 seconds on a standard
      personal computer. It is fully automatic and gives the user control over the
      entire process. CONCLUSION: Despite its limitations in modeling and validation,
      this practical solution provides a rapid and potentially useful qualitative
      assessment of anatomy deformed by a mass effect tumor.

PMID- 16087101
TI  - Radiofrequency ablation for common atrial flutter using an 8-mm tip catheter and
      up to 150 W.
AB  - The formation of bi-directional block in atrial flutter can be adversely affected
      by problems with the delivery of effective energy related to isthmus anatomy and
      contact. Higher energies can produce larger and more effective lesions. The
      optimum setting for power delivery using temperature controlled ablation has not
      been established, with the maximum reported being 100 W. This is a retrospective
      review of the first 50 new cases assessing the efficacy and safety of using
      temperature controlled (60-65 degrees C) flutter ablation with an 8mm tip
      electrode catheter and up to 150 W. All cases had either typical flutter alone
      (34%) or predominant flutter as the indication, no combined procedures were
      included. Acute procedural success was 94% and long-term success of 88%. Median
      number of ablations required was 11 (interquartile range 10-19), median procedure
      time 120 min (IQR 102-164), fluoroscopy time 22 min (IQR 17-36), radiation dose
      17 Gy cm(2) (IQR 10-27), median number of lines 1 (IQR 1-2). Six patients
      achieved 150 W, but 42 achieved >100 W (median watts 142 W, IQR 104-147).
      Patients (12%) experienced an uncomplicated pop during the procedure. None
      experienced a significant complication. There were three late relapses. The
      setting of 150 W maximum delivered energy in temperature regulated ablation
      allowed higher energies (>100 W) to be delivered in most patients. This resulted
      in acute and long-term success rates that compare well with the literature but is
      associated with a 12% rate of pop. Subsequent to this series our 54th patient
      sustained a pop due to high energy ablation that resulted in perforation and
      tamponade, from which there was survival.

PMID- 16087102
TI  - Atrial flutter: Watch and control?

PMID- 16087103
TI  - Increased resting heart rate following radiofrequency catheter ablation for
      atrial fibrillation.
AB  - AIM: Sinus tachycardia has been observed following radiofrequency (RF) catheter
      ablation for various kinds of supraventricular tachycardia. This study is aimed
      at determining the occurrence of changes in sinus-rhythm heart rate (HR) after
      pulmonary vein (PV) isolation in patients with paroxysmal/persistent atrial
      fibrillation (AF), prospectively. METHODS: Patients with a history of AF
      underwent segmental or circumferential isolation of the PVs. A total of 62
      consecutive patients, mean age 55 +/- 10, was included. Clinical evaluation was
      performed before and one, three, six, nine, and 12 months following the
      procedure. RESULTS: Following PV isolation, the mean HR significantly increased
      from 58 +/- 10 bpm at baseline to 67 +/- 12 bpm at one month, 71 +/- 13 bpm at
      three months, 69 +/- 12 bpm at six months, 69 +/- 13 at nine months, and 70 +/-
      13 at 12 months follow-up. The ablation success significantly correlated with the
      increase in HR at one month follow-up. In three patients the mean HR increased >
      25 bpm resulting in symptoms necessitating therapy with rate-controlling drugs.
      CONCLUSION: PV isolation in patients with AF may result in increased HR, which
      positively correlated with the ablation success. This change does not seem to
      resolve spontaneously after a follow-up of 12 months. Approximately 5% of
      patients may develop symptoms due to an increased HR, necessitating treatment
      with rate-controlling drugs.

PMID- 16087104
TI  - Complete pulmonary vein isolation guided by three-dimensional electroanatomical
      mapping for the treatment of paroxysmal atrial fibrillation in patients with
      hypertrophic obstructive cardiomyopathy.
AB  - AIMS: Evaluation of the clinical outcome of patients with hypertrophic
      obstructive cardiomyopathy (HOCM) and paroxysmal atrial fibrillation (AF) treated
      with complete pulmonary vein (PV) isolation guided by three-dimensional (3-D)
      electroanatomical (EA) mapping. METHODS: Circumferential radiofrequency (RF)
      ablation and continuous circular lesions (CCLs) around the left and right-sided
      PVs were performed in 4 highly symptomatic patients (2 males; age 57.5 +/- 8.3
      years) with HOCM and anti-arrhythmic drug (AAD) refractory paroxysmal AF.
      Ablation was guided by 3-D EA mapping combined with conventional circumferential
      PV mapping. The endpoints of the ablation were defined as: (1) absence of all PV
      spikes documented with the two Lasso catheters within the ipsilateral PVs; and
      (2) no recurrence of the PV spikes within all PVs following intravenous
      administration of adenosine. RESULTS: The ablation endpoints were achieved in all
      patients. A repeat ablation was performed in one patient due to repetitive atrial
      tachycardia, 1 month after the initial procedure. During a follow-up of 5.8 +/-
      2.7 months, all patients are free of AF recurrence. Short episodes of symptomatic
      AT were documented after the repeat procedure, and were well controlled with oral
      amiodarone in the patient. No procedure-related complications were observed.
      CONCLUSION: The present study demonstrates that complete isolation of ipsilateral
      PVs guided by 3-D EA mapping is potentially effective for the treatment of highly
      symptomatic, drug refractory paroxysmal AF in patients with HOCM.

PMID- 16087105
TI  - Coronary sinus mapping to differentiate left versus right ventricular outflow
      tract tachycardias.
AB  - Outflow tract ventricular tachycardia (OT-VT) can originate from several
      different segments of the outflow tract. Various ECG criteria have been proposed
      for localization of OT-VTs. We present two patients, one with left and one with
      right OT-VT. We used local ventricular electrograms in the coronary sinus to
      localize the focus of the OT-VT. Mapping of local ventricular electrograms in the
      coronary sinus may be a simple and effective method for differentiating right
      versus left ventricular outflow tract tachycardias. However, the diagnostic value
      and precision of this method should be evaluated in a series of patients before
      its implementation in the OT-VT ablation decision algorithm.

PMID- 16087106
TI  - Sustained ventricular tachycardia induced by dobutamine stress echocardiography:
      a prospective study.
AB  - AIMS: To investigate the prognostic significance and electrophysiological
      characteristics of dobutamine stress echo (DSE)-induced sustained monomorphic
      ventricular tachycardia (VT). METHODS: In our department, 3022 DSE studies were
      carried out on 2688 patients, aged 54.7 +/- 11.8 years, over a 3.5 year period.
      Patients with DSE-induced VT were studied by means of coronary angiography and
      electrophysiological testing, and were followed-up for 17.8 +/- 9.3 months.
      RESULTS: During DSE, nine patients (0.3%) developed sustained monomorphic VT.
      Four patients had coronary artery disease, one developed spontaneous right
      coronary artery (RCA) dissection during DSE, one patient had peripartum
      cardiomyopathy and the remainder had normal coronary arteries. Logistic
      regression analysis did not identify clinical parameters such as left ventricular
      ejection fraction, documentation of an ischaemic response or the presence of non
      viable myocardial segments during DSE, that could predict the occurrence of DSE
      induced VT. Monomorphic VT was inducible by electrophysiological testing in two
      patients with CAD and reduced LVEF. During follow-up, only these two patients
      developed VT. CONCLUSION: Sustained monomorphic VT is a rare complication of DSE,
      with no predictive value for the identification of patients with coronary artery
      disease and no prognostic significance in patients with normal coronary arteries.
      No predictors of its occurrence were identified.

PMID- 16087107
TI  - Is the activation potential of Mahaim pathway always a fast potential?
      Implication for radiofrequency catheter ablation.
AB  - INTRODUCTION: Accessory pathways (AP) exhibiting Mahaim physiology are amenable
      to radiofrequency (RF) catheter ablation. The recording of an AP potential is an
      excellent guide for selection of ablation site. The purpose of this study is to
      determine whether the pathway potential is always a fast potential. METHODS: Ten
      patients (six females, mean age, 30 +/- 12 years) with preexcited tachycardias
      involving a Mahaim pathway underwent electrophysiological study and subsequent
      attempts at RF ablation. Mahaim potentials (M-potential) recorded at the site of
      successful ablation were reviewed and classified by at least two reviewers.
      RESULTS: In all patients, Mahaim pathways were characterized as atriofascicular
      types. The M-potential was fast in seven patients (group one), and slow in the
      remaining patients (group two). All group two patients had a history of prior
      failed ablation. Atrial electrograms were recorded closer to the QRS onset in
      group one. Atrium to fast M-potential (42 +/- 15 ms) was shorter than atrium to
      slow M-potential (83 +/- 12 ms, P = 0.03) but M-potentials were recorded with
      similar distance before local ventricular electrogram (P = NS). Ablation was
      successful in all patients with mean of 2.9 +/- 1.4 RF applications per patient.
      Ablation data were similar between the two groups (P = NS). No complications
      occurred. During 12 months of follow-up, no recurrence was observed. CONCLUSION:
      Our results illustrated that the activation potential of Mahaim pathways is not
      always a fast potential. One-third of Mahaim pathways can be mapped and ablated
      when the slow type of M-potential was used as a target for ablation. We also
      confirmed high efficacy of catheter ablation of Mahaim pathways guided by
      activation potentials.

PMID- 16087108
TI  - Electrocardiographic predictors of Brugada type response during Na channel
      blockade challenge.
AB  - AIM: To identify ECG predictors of Brugada type response during Na channel
      blockade challenge. METHODS: We studied prospectively 103 patients (M = 76, 45 +/
      13 years) in whom ECGs were collected during ajmaline challenge. ECG recordings
      included the high right precordial leads (-2V(1) and -2V(2)). A positive response
      was defined by a >0.2 mV J point or ST segment elevation and a down-sloping
      pattern of the ST segment in at least one right precordial lead. RESULTS:
      Ajmaline challenge was positive in 48 (47%) of the 103 cases. Baseline J wave
      elevation was greater in -2V(1) (0.077 +/- 0.078 mV vs. 0.038 +/- 0.046 mV, P =
      0.003) and -2V(2) (0.149 +/- 0.103 mV vs. 0.043 +/- 0.088 mV, P < 0.001) in cases
      with a subsequent positive response. In contrast, ST segment elevation and T wave
      amplitudes were reduced in V(1), V(2) and V(3). Logistic regression showed that J
      wave elevation in -2V(2) and decreased T wave amplitude in V(3) at baseline were
      independent predictors of a positive response. Baseline J wave elevation >0.16 mV
      in -2V(2) had a specificity of 100%, a sensitivity of 40%, a positive predictive
      value of 100% and a negative predictive value of 28%. CONCLUSION: J wave
      elevation >0.16 mV in -2V(2) was the strongest predictor of a Brugada type
      response to Na channel blockade challenge when Brugada syndrome was suspected on
      a baseline ECG.

PMID- 16087109
TI  - Rate stabilization by right ventricular apex or His bundle pacing in patients
      with atrial fibrillation.
AB  - AIMS: In patients with atrial fibrillation right ventricular pacing can block
      antegrade conduction at pacing intervals longer than the shortest spontaneous R-R
      interval, causing the stabilization of ventricular rhythm. In this study the
      effects of pacing at two sites were compared in order to evaluate the role of
      conduction times in determining the stabilization of ventricular rhythm. METHODS:
      In eight patients with permanent atrial fibrillation, the ventricular rate was
      recorded before and during pacing at the right ventricular apex and the His
      bundle with different cycle lengths. RESULTS: In all patients, we obtained a
      reduction in spontaneous QRS complexes with respect to those anticipated at
      pacing rates slightly above the spontaneous mean rate, and the ventricular rhythm
      stabilized at pacing intervals longer than the spontaneous shortest R-R
      intervals. Between pacing sites we did not observe any difference in the
      reduction in spontaneous beats and the cycle stabilizing the rhythm. Moreover,
      simulation of the interaction between antegrade and retrograde impulses in a
      computer model confirmed that results obtained by pacing at the His bundle cannot
      be readily explained as a consequence of conduction delays. CONCLUSION: This
      study suggests that the lag introduced by the His-Purkinje conduction cannot
      explain, as proposed, the stabilization of ventricular rhythm observed in
      patients with atrial fibrillation and right ventricular pacing.

PMID- 16087110
TI  - Cerebral blood flow during supine rest and the first minute of head-up tilt in
      patients with orthostatic intolerance.
AB  - AIM: To assess the cerebral blood flow velocity during the first minute of head
      up tilt in patients with postural tachycardia syndrome (POTS) or neurally
      mediated reflex syncope compared with patients with dizziness. METHODS: We
      evaluated 120 patients selected from 470 patients who underwent head-up tilt
      testing: 40 with POTS, 40 with typical neurally-mediated reflex syncope and 40
      who complained of dizziness with no history of loss of consciousness and a
      negative head-up tilt test (with and without isosorbide). Transcranial Doppler
      sonography of the middle cerebral artery, heart rate and brachial blood pressure
      were recorded during a 70 degrees head-up tilt test. RESULTS: During both
      baseline in supine position and the first minute of upright tilt, patients with
      postural tachycardia syndrome showed higher heart rate and cerebral blood flow
      velocity than patients with dizziness and patients with neurally-mediated reflex
      syncope (P < 0.05, ANOVA), but no significant difference was observed on the
      Gosling's pulsatility index. CONCLUSION: Patients with POTS have an autonomic
      dysfunction that is not triggered by upright posture but is accentuated by it.

PMID- 16087111
TI  - Psychiatric profile, quality of life and risk of syncopal recurrence in patients
      with tilt-induced vasovagal syncope.
AB  - AIM: The aim of this study was to investigate the prevalence of psychiatric
      disorders and quality of life (QoL) in patients with tilt-induced vasovagal
      syncope and no other comorbidities, and their relationship with the syncopal
      burden and the risk of recurrence. METHODS: We studied 61 patients with recurrent
      syncope and positive tilt testing. Controls consisted of 61 sex- and age-matched
      healthy subjects. Psychiatric diagnoses were formulated on the basis of a
      structured interview and the Minnesota Multiphase Personality Inventory-2
      questionnaire. QoL was assessed by means of the Short-Form Health Survey
      questionnaire. Patients were followed up for at least 1 year. RESULTS: The
      presence of psychiatric disorders was higher among patients than controls (71%
      vs. 23%, P < 0.001), with a prevalence of anxiety (28% vs. 5%), mood (18% vs.
      3%), and somatization disorders (29% vs. 3%). The scores of all the QoL scales
      were statistically lower in patients than controls. An inverse correlation was
      found between QoL scale scores and syncopal burden. The presence of psychiatric
      disorders was predictive of syncopal recurrence during follow-up. CONCLUSION:
      Psychiatric disorders are common in patients with tilt-induced vasovagal syncope,
      and seem to predict the risk of recurrence. QoL is impaired in these patients,
      and is inversely correlated with the syncopal burden.

PMID- 16087112
TI  - Familial vasovagal syncope.
AB  - Vasovagal syncope (VVS) is a common clinical problem characterized by transient
      episodes of loss of consciousness due to abnormal autonomic activity. This paper
      describes two groups of monozygotic twins, from different families, affected by
      VVS and a family with several members with this condition. Their clinical
      characteristics, haemodynamic response to tilt, treatment, and outcome are
      described.

PMID- 16087113
TI  - The coronary sinus conduit function: anatomical study (relationship to adjacent
      structures).
AB  - BACKGROUND: The mitral valve annulus (MVA) is anchored antero-medially to the
      aorta. Dilatation of the MVA primarily affects its postero-lateral aspect, which
      is related to the coronary sinus (CS). The CS and its tributaries have been used
      for pacing the left ventricle in patients with intractable heart failure. The aim
      of this study was to determine anatomical relations between the CS and its
      adjacent structures in 40 adult normal cadaveric heart specimens. METHODS: In 32
      specimens, longitudinal sections were made along the free circumference of the
      MVA in 6 separate regions, 36 degrees between each, with the 0 degree marked by a
      line joining the centre of the CS ostium and that of the MV. In each section, the
      relations of the CS to the circumflex artery and the MVA were determined. CS
      diameter and its distance from the endocardium, just below the MVA, were also
      measured by a digital calliper. RESULTS: The great cardiac vein (GCV) diameter is
      5.6 +/- 1.6 mm. As it leaves the interventricular groove, it curves to the left
      forming the base of the triangle of "Brocq and Mouchet" with the two branches of
      the left coronary artery, having a triple relationship with the circumflex
      artery. It then continues as the CS (diameter 9.3 +/- 5.3 mm) in the inferior
      atrioventricular groove. The end part of the GCV crosses superficial to the left
      circumflex artery at the level of the left marginal vein. The shortest distance
      between the wall of the CS and the endocardium adjacent to the MVA at the level
      of the anterolateral commissure is 5.2 +/- 1.6 mm, i.e. beyond the Vieussens
      valve. Thus, together with the CS the great cardiac vein, form a semicircular
      venous channel at the postero-lateral aspect of the MVA. In 37/40 hearts, this
      venous channel arches upwards in its middle part to be in direct contact with the
      left atrium. CONCLUSION: This study demonstrates an intimate proximity between
      the coronary sinus, at its beginning and end, and the mitral valve annulus. It
      also highlights the close relationship between the great cardiac vein, the
      annulus and the left ventricular free wall. Assessing the same relationship using
      the currently available imaging techniques should aid in the successful
      cannulation of the coronary sinus for various cardiological interventions.

PMID- 16087114
TI  - Brady-tachy syndrome: rapid atrial pacing efficacy in preventing atrial
      fibrillation recurrence assessed by reliable electrograms: the prefib pilot
      study.
AB  - AIMS: Recent studies have tested different atrial pacing rates, modes, and sites
      for preventing atrial fibrillation (AF) recurrence. Present generation pacemakers
      offer reliable electrograms (EGMs) storage for optimizing the arrhythmia
      diagnosis. Based on these EGMs, the study objective was to assess the rate of AF
      recurrence at two different pacing rates. METHODS: Thirty patients suffering
      exclusively from symptomatic brady-tachy syndrome (BTS) resistant to > or =2
      drugs, were implanted with a DDDR pacemaker. After a 5-days observation period,
      the DDD pacing rate was randomly programmed at 60 bpm (-15 bpm hysteresis) or at
      80 bpm for 12 weeks. The two sequences were crossed over at the end of this fixed
      period or when earlier symptomatic AF recurred. Antiarrhythmics were maintained.
      Stored EGMs of > or =4 s duration identified all AF recurrence. RESULTS: Thirty
      patients (17 males, 77.2 +/- 8.1 years old) were included. One patient withdrew
      prematurely for severe heart failure associated with AF recurrence and rapid
      ventricular response. For the remainder of the 29 patients, fast atrial pacing
      neither provoked symptoms nor haemodynamic change. AF recurred in 16 patients
      paced at 60 (-15) bpm (mean time: 29 days; range 1-61) and in 9 patients paced at
      80 bpm (mean time: 55 days; range 5-83) (P < 0.05). AF recurrence was
      asymptomatic in 50% of patients. CONCLUSIONS: These results confirm that rapid
      atrial pacing is 1) significantly effective for preventing AF recurrence in
      symptomatic BTS patients, and 2) haemodynamically well tolerated.

PMID- 16087115
TI  - Biventricular pacing in a patient with ventilatory and inotropic dependant heart
      failure following coronary artery by-pass surgery.
AB  - Resynchronisation of intra- and interventricular conduction delay by
      biventricular pacing has become a proven therapy for selected heart failure
      patients. We present a case of biventricular pacing, used with great success, as
      a 'bail out' for a patient with refractory congestive heart failure following by
      pass surgery.

PMID- 16087116
TI  - Anticoagulation in atrial fibrillation and flutter.
AB  - Atrial fibrillation and atrial flutter are important risk factors for stroke.
      Based on a literature search, pathogenesis of thromboembolism, risk assessment in
      patients, efficacy of anticoagulation therapy and its alternatives are discussed.
      Special emphasis is put on issues like paroxysmal atrial fibrillation, atrial
      flutter and anticoagulation surrounding catheter ablation and cardioversion. A
      strategy for anticoagulation around the time of pulmonary vein ablation is
      suggested.

PMID- 16087117
TI  - Prediction of maintenance of sinus rhythm after electrical cardioversion of
      atrial fibrillation by non-deterministic modelling.
AB  - AIMS: Atrial fibrillation (AF) is the most common rhythm disorder. Because of the
      high recurrence rate of AF after cardioversion and because of potential side
      effects of electrical cardioversion, it is clinically important to predict
      persistence of sinus rhythm after electrical cardioversion before it is
      attempted. The aim of our study was the development of a mathematical model by
      "genetic" programming (GP), a non-deterministic modelling technique, which would
      predict maintenance of sinus rhythm after electrical cardioversion of persistent
      AF. PATIENTS AND METHODS: Ninety-seven patients with persistent AF lasting more
      than 48h, undergoing the first attempt at transthoracic cardioversion were
      included in this prospective study. Persistence of AF before the cardioversion
      attempt, amiodarone treatment, left atrial dimension, mean, standard deviation
      and approximate entropy of ECG R-R intervals were collected. The data of 53
      patients were randomly selected from the database and used for GP modelling; the
      other 44 data sets were used for model testing. RESULTS: In 23 patients sinus
      rhythm persisted at 3 months. In the other 21 patients sinus rhythm was not
      achieved or its duration was less than 3 months. The model developed by GP failed
      to predict maintenance of sinus rhythm at 3 months in one patient and in six
      patients falsely predicted maintenance of sinus rhythm. Positive and negative
      likelihood ratios of the model for testing data were 4.32 and 0.05, respectively.
      Using this model 15 of 21 (71.4%) cardioversions not resulting in sinus rhythm at
      3 months would have been avoided, whereas 22 of 23 (95.6%) cardioversions
      resulting in sinus rhythm at 3 months would have been administered. CONCLUSION:
      This model developed by GP, including clinical data, ECG data from the time
      domain and nonlinear dynamics can predict maintenance of sinus rhythm. Further
      research is needed to explore its utility in the present or an expanded form.

PMID- 16087118
TI  - Identification of hepatitis B virus X gene mutation in Hong Kong patients with
      hepatocellular carcinoma.
AB  - BACKGROUND: Chronic infection by hepatitis B virus (HBV) is the leading cause of
      hepatocellular carcinoma (HCC) in man. The viral transactivator HBV X (HBx) gene
      plays a critical role in the molecular pathogenesis of HBV-related HCC.
      OBJECTIVES: The aim of this study was to investigate whether there were
      particular HBx mutations associated with the Chinese Hong Kong patients with HCC.
      STUDY DESIGN: We have examined HBx in 113 tumor tissue samples from patients with
      HCC and 48 serum samples from the same group. In addition, we also examined the
      expression of HBx protein and the index of apoptotic cell death in tumor tissues
      of HCC. The entire coding region of HBx gene from the sample was sequenced and
      aligned with the published HBx gene sequence. RESULTS AND CONCLUSIONS: We have
      identified total 54 different types of mutations in HBx gene. HBx mutations
      occurred in a very high percentage of samples tested. Mutation of HBx was found
      in 95.2% and 95.3% of the tumor tissue and serum samples, respectively. Most of
      samples contained more than one type of the mutation. Relative risk analysis
      indicated that the mutations in 12 sites of tissue HBx and nine sites of serum
      HBx were highly associated with HCC, suggesting a potential role of these mutants
      in carcinogenesis. An insert mutation at position 204: Insert 204AGGCCC, was
      always found to co-exist with point mutations at 260 (G-->A) and 264 (G/C/T-->A).
      Furthermore, this particular pattern of HBx mutation was most frequently
      detected. Immunochemical staining of HBx protein revealed that the nuclear
      localization of HBx protein in hepatocytes of tumor tissues was highly associated
      with this particular pattern of HBx mutation. In conclusion, HBx mutation occurs
      frequently in HCC samples tested and a sample usually has multiple types of
      mutations. A special pattern of insert at 204 and point mutations at 260 and 264
      was identified, and it appears to be associated with the nuclear localization of
      HBx protein. The development of multiple types of mutations in a given sample may
      contribute to the process of multiple steps in hepatocarcinogenesis.

PMID- 16087119
TI  - Characterisation of rotavirus strains among hospitalised and non-hospitalised
      children in Guinea-Bissau, 2002 A high frequency of mixed infections with
      serotype G8.
AB  - BACKGROUND: In a previous community-based cohort study in Guinea-Bissau from 1996
      to 1998, characterisation of rotavirus strains showed a high frequency of less
      common genotypes such as G8 and G9 and a high proportion of mixed infections.
      OBJECTIVES AND STUDY DESIGN: In the present study, we examined the prevalence of
      rotavirus genotypes among 81 hospitalised and 23 non-hospitalised Guinean
      children with rotavirus associated diarrhoea during the 2002 seasonal rotavirus
      outbreak. G- and P-types were determined in a two-step procedure using reverse
      transcription followed by a standard multiplex PCR. The multiplex PCR for G-types
      was furthermore supplemented with a single locus PCR including the MW8 primer for
      the G8-genotype. RESULTS: The dual infection G2/P[4]P[6] (24%) appeared to be the
      most frequent cause of rotavirus infections followed by G2P[4] (19%), G2P[6]
      (16%) and G8P[6] (13%). Overall 38% of the infections were mixed and 18% of the
      samples had the genotype G8. However, by subjecting all samples and not only the
      strains, which according to the standard multiplex PCR procedure were non
      typeable, to a single locus G8-PCR, we found that the genotype G8 appeared in 62%
      of the infections, either as a single G-strain or in combination with other G
      types, especially G2. Including these results, more than 63% of infections
      emerged as mixed. Neither genotype (including the presence of G8) nor the
      presence of mixed infections, seem to influence the severity of the rotavirus
      infection. CONCLUSION: We found a high frequency of mixed infections especially
      due to G8-genotypes, which might have implications for development of rotavirus
      vaccine candidates for use in Africa. Our results do not suggest that a single
      genotype is associated with severity, but the present study is based on a modest
      number of samples and results should be interpreted with caution.

PMID- 16087120
TI  - First external quality assurance of antibody diagnostic for SARS-new coronavirus.
AB  - To confirm an infection with the new coronavirus (SARS-CoV) causing the severe
      acute respiratory syndrome (SARS) diagnostic assays for detection of SARS-CoV
      specific antibody are necessary. To evaluate the diagnostic performance of
      laboratories an external quality assurance (EQA) study was performed in 2004.
      Participating laboratories (9/20) correctly detected anti-SARS antibodies in
      serum samples without false positive results in an immunofluorescence assay. In
      contrast, only 4/13 laboratories detected most of the anti-SARS antibody positive
      samples without false positive results using enzyme immunoassays (EIA) and/or
      immunoblot. The overall results clearly demonstrate that serological diagnosis of
      SARS-CoV remains at an early stage of development, with further technical
      improvements required, particularly with respect to the use of SARS specific
      EIAs.

PMID- 16087121
TI  - Epstein-Barr virus encoded BALF1 gene is transcribed in Burkitt's lymphoma cell
      lines and in nasopharyngeal carcinoma's biopsies.
AB  - BACKGROUND: The Epstein-Barr virus (EBV) encodes two anti-apoptotic cellular Bcl2
      homologs, BALF1 and BHRF1. BHRF1 has an anti-apoptotic activity but is rarely
      expressed in nasopharyngeal carcinoma (NPC). However, BALF1 is not yet well
      characterized. OBJECTIVES: The objective of the study was to characterize BALF1
      gene. First, the search of its transcriptional expression in EBV-positive B cell
      lines, EBV-positive Burkitt's lymphoma's cell lines and nasopharyngeal
      carcinoma's biopsies. Second, the examination of its anti-apoptotic activity in
      serum dependent assays. STUDY DESIGN: We first analysed the transcriptional
      expression of BALF1 by reverse transcriptase DNA polymerase chain reaction (RT
      PCR) method. For the analysis of its anti-apoptotic activity, we transfected
      NIH3T3 cells with pBABE-BALF1 expression plasmid and studied serum dependence of
      these transfectants. RESULTS: BALF1 expression was detected in the latent stage
      and increased more significantly during the lytic phase in IgG-treated AKATA and
      TPA-SB-treated P3HR1-TK negative cell lines. As its expression was not affected
      by the inhibitor of viral DNA synthesis, this gene does not belong to late gene
      family. When analysed its transcription in Burkitt's lymphoma (BL)-derived cell
      lines and NPC biopsies, all BL-derived cell lines and more than 80% of NPC
      biopsies transcribed this gene. The study of serum dependence of BALF1
      transfected NIH3T3 cells showed: with 10% of serum, BALF1 transfectants grew
      significantly more higher cell density than vector alone transfected NIH3T3 cell
      lines and with 1% of serum, BALF1 transfectants were capable of growing, but with
      about 40% reduced rate in comparison with those with 10% serum, while vector
      alone transfected NIH3T3 cells could not almost grow. CONCLUSION: BALF1 gene was
      transcribed in EBV-associated tumor cells. BALF1 could render cells to serum
      independent. These results suggest that BALF1 gene could play its role in EBV
      oncogenesis.

PMID- 16087122
TI  - A phage-displayed cyclic peptide that interacts tightly with the immunodominant
      region of hepatitis B surface antigen.
AB  - The surface antigen (HBsAg) of hepatitis B virus (HBV) is highly conformational
      and generally evokes protective humoral immune response in human. A disulfide
      constrained random heptapeptide library displayed on the coat protein III of
      filamentous bacteriophage M13 was employed to select specific ligands that
      interact with HBsAg subtype ad. Fusion phages carrying the amino acid sequence
      ETGAKPH and other related sequences were isolated. The binding site of peptide
      ETGAKPH was located on the immunodominant region of HBsAg. An equilibrium binding
      assay in solution showed that the phage binds tightly to HBsAg with a relative
      dissociation constant (KDrel) of 2.9+/-0.9 nM. The phage bearing this peptide has
      the potential to be used as a diagnostic reagent and two assays for detecting
      HBsAg in blood samples are described.

PMID- 16087123
TI  - Comparison of GB virus C, HIV, and HCV infection markers in hemophiliacs exposed
      to non-inactivated or inactivated factor concentrates.
AB  - BACKGROUND: Until the mandatory introduction of viral inactivation techniques of
      blood plasma products in the early 1980s many recipients of these products were
      infected with various viral pathogens. OBJECTIVES: To determine the rate of
      transmission of GB virus C/hepatitis G virus (GBV-C/HGV) HCV, and HIV through non
      virus-inactivated clotting factor concentrates in hemophiliacs, as well as the
      relation between amount of administered clotting factor and risk for GBV-C/HGV
      infection. STUDY DESIGN: In this cross-sectional study, we determined
      retrospectively the rates of infection markers for GBV-C/HGV, HCV, and HIV in a
      German cohort of hemophiliacs treated with documented amounts of non-virus
      inactivated clotting factor concentrates (group A) and in a second group of
      hemophiliacs who were treated exclusively with virus-inactivated clotting factor
      (group B). The presence of anti-virus antibodies was determined by ELISA. Viral
      RNA was detected by RT-PCR. Markers for viral infections were compared to amounts
      of administered non-virus-inactivated clotting factor. RESULTS: Among
      hemophiliacs treated with documented amounts of non-virus-inactivated clotting
      factor the prevalence for GBV-C/HGV, HCV, and HIV was 40.3%, 98.6%, and 56.3%,
      respectively. In contrast to HIV, the rate of GBV-C/HGV infections did not
      increase with increasing amounts of consumed non-inactivated clotting factor.
      Even in the subgroup of heavily treated hemophiliacs the rate of GBV-C/HGV
      infection markers did not exceed 45%. CONCLUSIONS: The amount of non-virus
      inactivated clotting factor is not predictive for the risk of GBV-C/HGV infection
      in hemophiliacs. Despite repeated parenteral exposure more than 55% of
      hemophiliacs were not infected with GBV-C/HGV. Our findings indicate a high
      frequency of host factors preventing parenteral transmission of GBV-C/HGV.

PMID- 16087124
TI  - Human parainfluenza virus type 4 infections: a report of 20 cases from 1998 to
      2002.
AB  - BACKGROUND: Human Parainfluenza Viruses (HPIV) type 4 are responsible for
      respiratory infections. Unlike HPIV types 1-3, they are associated with mild
      infections and appear to be infrequent. Thus, they often go undetected. STUDY
      DESIGN: From 1998 to 2002, in 20 respiratory samples of hospitalised patient, we
      isolated viruses presenting a large syncytial cytopathic effect when inoculated
      on LLC-MK2 cells. Most of the patients (16/20) were young infants and all of them
      presented with respiratory infections. RESULTS: We detected 18 cases during
      autumn and winter, 1 case during spring and 1 during summer. We could not
      identify these viruses using the panel of routine assays. Samples were then
      analysed by specific HPIV 4 RT-PCR and IF assays. All the samples were scored
      positive with both methods. CONCLUSION: We conclude that HPIV 4 infections are
      probably underestimated. Their role in viral respiratory infections should be
      carefully investigated using techniques adapted to their detection and culture.

PMID- 16087125
TI  - Specific and quantitative detection of human polyomaviruses BKV, JCV, and SV40 by
      real time PCR.
AB  - BACKGROUND: The polyomaviruses that infect humans, BK virus (BKV), JC virus
      (JCV), and simian virus 40 (SV40), typically establish subclinical persistent
      infections. However, reactivation of these viruses in immunocompromised hosts is
      associated with renal nephropathy and hemorrhagic cystitis (HC) caused by BKV and
      with progressive multifocal leukoencephalopathy (PML) caused by JCV.
      Additionally, SV40 is associated with several types of human cancers including
      primary brain and bone cancers, mesotheliomas, and non-Hodgkin's lymphoma.
      Advancements in detection of these viruses may contribute to improved diagnosis
      and treatment of affected patients. OBJECTIVE: To develop sensitive and specific
      real time quantitative polymerase chain reaction (RQ-PCR) assays for the
      detection of T-antigen DNA sequences of the human polyomaviruses BKV, JCV, and
      SV40 using the ABI Prism 7000 Sequence Detection System. STUDY DESIGN: Assays for
      absolute quantification of the viral T-ag sequences were designed and the
      sensitivity and specificity were evaluated. A quantitative assay to measure the
      single copy human RNAse P gene was also developed and evaluated in order to
      normalize viral gene copy numbers to cell numbers. RESULTS: Quantification of the
      target genes is sensitive and specific over a 7 log dynamic range. Ten copies
      each of the viral and cellular genes are reproducibly and accurately detected.
      The sensitivity of detection of the RQ-PCR assays is increased 10- to 100-fold
      compared to conventional PCR and agarose gel protocols. The primers and probes
      used to detect the viral genes are specific for each virus and there is no cross
      reactivity within the dynamic range of the standard dilutions. The sensitivity of
      detection for these assays is not reduced in human cellular extracts; however,
      different DNA extraction protocols may affect quantification. CONCLUSION: These
      assays provide a technique for rapid and specific quantification of polyomavirus
      genomes per cell in human samples.

PMID- 16087126
TI  - Characterization of soluble FAS, FAS ligand and tumour necrosis factor-alpha in
      patients with chronic HCV infection.
AB  - BACKGROUND: There are limited reports on the role of the cell surface receptor
      Fas and its ligand molecule in mediating apoptosis during infection with the
      hepatitis C virus (HCV). OBJECTIVES: The aims of this study were (1) to assess
      the susceptibility of the Fas antigen expressed on peripheral blood mononuclear
      cells to Fas ligand-induced-death in patients with chronic HCV infection and (2)
      to investigate the correlation between the plasma levels of soluble Fas (sFas),
      soluble Fas ligand (sFasL), tumour necrosis factor-alpha (TNF-alpha), alanine
      amino transferase (ALT), and HCV viral load. STUDY DESIGN: The susceptibility of
      peripheral blood mononuclear cells from 17 subjects with chronic HCV infection to
      Fas ligand induced cell death was assessed using a water soluble tetrazolium
      assay. The plasma levels of associated markers such as sFas, sFasL, and TNF-alpha
      were quantified using immunoassays. ALT values were obtained from hospital
      records. Viral loads were quantified using a commercially available quantitative
      assay--the Amplicor Monitor (version 2.0). Controls for comparison included a
      group of healthy individuals and individuals infected with the human
      immunodeficiency virus 1. RESULTS: The percentage of cell death induced in
      hepatitis C virus infected individuals was lower than that seen in the healthy
      control group. Patients infected with HCV had higher average values of sFas and
      TNF-alpha as compared to both control groups. Plasma levels of sFas in patients
      with chronic HCV infection showed significant positive correlations to ALT and
      TNF-alpha levels. TNF-alpha levels also showed a significant positive correlation
      with ALT levels. CONCLUSIONS: PBMC in HCV infection exhibit decreased
      susceptibility to Fas ligand induced cell death. This may signify a means by
      which HCV escapes immune surveillance. This phenomenon merits further
      investigation. The strong correlations observed between plasma sFas, ALT and TNF
      alpha suggest a potential role for these markers as an alternative to an invasive
      liver biopsy.

PMID- 16087127
TI  - Exploring symptoms in chronic heart failure.
AB  - Symptoms in patients with chronic heart failure (CHF) are the cry for help,
      reflecting not only the physical aspects of the disease but the impact on
      lifestyle, anxiety, depression and expectations of the patient. Studies
      consistently show a difference in patients' self-assessed functional
      classification compared to investigator reported NYHA classification. Moreover,
      patient self-assessed symptoms have recently been shown to independently predict
      hospitalisation and mortality over 5 years. Recognition of symptoms and
      appreciation of their importance justifies the use of a structured assessment in
      order to provide optimal medical care for patients with CHF. A model of how to
      structure symptom assessment equally with signs is presented in this paper.

PMID- 16087128
TI  - Surgical left ventricular remodeling in heart failure.
AB  - The high mortality and morbidity of patients in terminal heart failure are a
      therapeutic challenge to modern medicine. Surgically, cardiac transplantation is
      an excellent treatment for many patients. However, lack of donors combined with
      an increasing number of patients has led to the search for other surgical
      strategies. Patients with symptomatic large left ventricular aneurysms have been
      treated with resection of the aneurysm and closure of the left ventricle either
      directly (linear closure, first reported by Cooley) or by implantation of a patch
      (endoventricular patch plasty or Dor procedure). Akinetic areas of the left
      ventricle have also been successfully treated by the latter method. According to
      the law of Laplace, large dilated ventricles have increased wall tension and thus
      increased oxygen consumption. Based on this fact, Batista and coworkers have
      reduced the volume of enlarged left ventricles in patients in terminal heart
      failure by removing a wedge of myocardium from the apex of the heart towards the
      base of the left ventricular free wall. Although a favorable outcome has been
      reported in selected patients, this method is currently not recommended for
      treatment of heart failure because of high surgical failure rates. The present
      paper reviews some of the relevant literature regarding surgical left ventricular
      remodeling in heart failure. Two new techniques (Myosplint and CorCap cardiac
      support device) are also briefly described.

PMID- 16087130
TI  - Left ventricular SERCA2a gene down-regulation does not parallel ANP gene up
      regulation during post-MI remodelling in rats.
AB  - BACKGROUND: In most animal models of chronic hemodynamic overload of the left
      ventricle (LV) as well as in human end stage heart failure, the sarcoplasmic
      reticulum (SR) Ca2+-ATPase (SERCA2a) mRNA levels are decreased in parallel with
      increased atrial natriuretic peptide (ANP) mRNA levels. The situation in the
      remote myocardium following myocardial infarction (MI) is unclear. AIMS: (1) To
      examine SERCA2a mRNA levels in the non-infarcted LV myocardium of rats at the
      chronic stage of experimental MI and (2) To examine whether a negative linear
      correlation exists between SERCA2a and ANP mRNA levels in this model. METHODS:
      Anesthetized adult male Wistar rats underwent left coronary artery ligation or
      sham operation. Three months later, the rats were divided into three groups: sham
      operated rats (sham, n=21), HF-free rats with MI (non-failing (NF)-MI, n=29) and
      rats with both MI and HF (congestive heart failure (CHF)-MI, n=14). LV
      remodelling and function were assessed by echocardiography and hemodynamic
      measurements. SERCA2a and ANP mRNA levels were determined by Northern and dot
      blot analysis with specific cDNA probes. RESULTS: LV SERCA2a mRNA levels varied
      markedly in sham-operated rats (0.9-1.8). Mean ANP mRNA level increased markedly
      and mean SERCA2a mRNA level decreased moderately in the remote myocardium. In
      some NF-MI rats, SERCA2a mRNA levels were higher than those in some sham
      controls. Whereas ANP mRNA levels correlated well with MI severity (r2=0.79,
      p<0.001), this was not the case for SERCA2a mRNA levels (r2=0.42, p<0.01). We
      found no negative correlation between ANP and SERCA2a mRNA levels. CONCLUSION:
      SERCA2a gene down-regulation in the non-infarcted myocardium of rats with MI does
      not correlate with ANP gene up-regulation, suggesting that the two genes are not
      antithetically regulated.

PMID- 16087129
TI  - Practical recommendations for the use of ACE inhibitors, beta-blockers,
      aldosterone antagonists and angiotensin receptor blockers in heart failure:
      putting guidelines into practice.
AB  - Surveys of prescribing patterns in both hospitals and primary care have usually
      shown delays in translating the evidence from clinical trials of pharmacological
      agents into clinical practice, thereby denying patients with heart failure (HF)
      the benefits of drug treatments proven to improve well-being and prolong life.
      This may be due to unfamiliarity with the evidence-base for these therapies, the
      clinical guidelines recommending the use of these treatments or both, as well as
      concerns regarding adverse events. ACE inhibitors have long been the cornerstone
      of therapy for systolic HF irrespective of aetiology. Recent trials have now
      shown that treatment with beta-blockers, aldosterone antagonists and angiotensin
      receptor blockers also leads to substantial improvements in outcome. In order to
      accelerate the safe uptake of these treatments and to ensure that all eligible
      patients receive the most appropriate medications, a clear and concise set of
      clinical recommendations has been prepared by a group of clinicians with
      practical expertise in the management of HF. The objective of these
      recommendations is to provide practical guidance for non-specialists, in order to
      increase the use of evidenced based therapy for HF. These practical
      recommendations are meant to serve as a supplement to, rather than replacement
      of, existing HF guidelines.

PMID- 16087131
TI  - C-reactive protein co-expresses with tumor necrosis factor-alpha in the
      myocardium in human dilated cardiomyopathy.
AB  - BACKGROUND: C-reactive protein (CRP) has recently been reported to be present in
      cardiac tissue and to stimulate the production of proinflammatory cytokines.
      Cardiac expression of tumor necrosis factor-alpha (TNF-alpha) plays an important
      role in the pathogenesis of dilated cardiomyopathy (DCM). AIMS: To determine
      whether CRP co-expresses with TNF-alpha in the myocardium and to examine its
      association with clinical features in patients with DCM. METHODS AND RESULTS:
      Endomyocardial biopsy tissues were obtained from 41 DCM patients and 16 controls
      by right ventricular endomyocardial biopsy. Levels of CRP and TNF-alpha mRNA were
      measured by real-time RT-PCR. Immunohistochemistry and in situ hybridization were
      performed to identify the cellular sources of CRP and TNF-alpha. Both CRP and TNF
      alpha mRNA were expressed in myocardium obtained from DCM patients, but not in
      controls. A positive correlation was found between CRP and TNF-alpha levels.
      CRP/TNF-alpha double staining was found to be colocalized in the cardiomyocytes
      of DCM patients. Both forms of mRNA were also expressed in cardiomyocytes. Both
      CRP and TNF-alpha mRNA levels were negatively correlated with systolic function
      and positively correlated with left ventricular volume in DCM patients. These
      mRNA levels were lower in DCM patients treated with a combination of
      spironolactone and either angiotensin-converting enzyme inhibitors (ACEIs) or
      angiotensin II type 1 receptor blockers (ARBs) than in patients not treated with
      these drugs. CONCLUSION: Cardiac expression of CRP with TNF-alpha may function as
      a proinflammatory mediator in DCM and may be related to the clinical severity of
      DCM. Expression of both of these proteins was decreased in DCM patients receiving
      spironolactone and either ACEIs or ARBs.

PMID- 16087132
TI  - Myocardial osteopontin expression is associated with collagen fibrillogenesis in
      human dilated cardiomyopathy.
AB  - BACKGROUND: Osteopontin (OPN), an extracellular matrix (ECM) protein, plays an
      important role in myocardial remodeling by promoting collagen synthesis and
      accumulation in experimental animal models. AIMS: We hypothesized that OPN could
      be expressed in myocardial tissues and contribute to collagen accumulation and
      myocardial dysfunction in human dilated cardiomyopathy (DCM). METHODS AND
      RESULTS: Endomyocardial biopsy tissues were obtained from 51 patients with DCM
      and 15 controls by right ventricular endomyocardial biopsy. OPN, collagen types I
      (Col I) and III (Col III) mRNA levels were measured by real-time reverse
      transcriptase polymerase chain reaction (RT-PCR). The cellular source of OPN was
      analyzed using immunohistochemistry and in situ hybridization. Myocardial
      collagen volume fraction (CVF) was determined by digital planimetry. OPN, Col I
      and Col III mRNA levels were higher in DCM patients than in controls (P<0.01).
      OPN mRNA levels were positively correlated with Col I levels and CVF in DCM
      patients (OPN vs. Col I: r=0.60, P<0.01; OPN vs. CVF: r=0.52, P<0.001).
      Immunostaining of OPN was present in cardiomyocytes from DCM patients. In situ
      hybridization identified cardiomyocytes as the major source of OPN mRNA
      transcription in DCM patients. OPN and Col I mRNA levels were highly expressed in
      the DCM subgroup with large left ventricular (LV) end-systolic diameter (LVESD >
      or = 54.5 mm) or low LV ejection fraction (LVEF < 29.5%). There was a weak
      positive correlation between OPN mRNA levels and LV end-systolic diameter
      (r=0.39, P<0.01). Levels of OPN mRNA were also negatively correlated with LV
      ejection fraction (r=-0.43, P<0.01). CONCLUSIONS: These results suggest that OPN
      may play a pivotal role in the development of Col-I-induced cardiac fibrosis and
      dysfunction in human DCM.

PMID- 16087133
TI  - Semiquantitative histomorphometric analysis of myocardium following partial left
      ventriculectomy: 1-year follow-up.
AB  - BACKGROUND: Although partial left ventriculectomy (PLV) may have beneficial
      clinical effects in patients with dilated cardiomyopathy (DCM), there are no
      reports on effects of PLV on myocardial histology. The objective of this study
      was to assess histological properties of the LV myocardium 1 year following PLV
      as compared to histology at the time of the operation. METHODS: The study group
      consisted of 15 consecutive PLV survivors, predominantly male (13/15), aged 45+/
      12 years. Surgical specimens and endomyocardial biopsies, taken 12 months
      postoperatively, were processed routinely and stained with Masson-trichrome. The
      following morphometric parameters were assessed semiquantitavely: (1) degree of
      hypertrophy and attenuation; (2) nuclear evidence of hypertrophy; (3)
      myofibrillar volume fraction; (4) degree of degenerative vacuolar changes; and
      (5) fibrosis volume fraction. RESULTS: Both New York Heart Association (NYHA)
      functional class and ejection fraction (EF) improved 12 months following surgery
      as compared to preoperative values (2.40+/-0.69 vs. 3.33+/-0.49, p<0.001, and
      33.21+/-12.05% vs. 20.21+/-9.07%, p<0.001, respectively). Morphometric analysis
      demonstrated postoperative decrease in the degree of attenuation as compared to
      preoperative values (1.40+/-0.51 vs. 2.47+/-0.64, p<0.01), as well as a decrease
      in fibrosis volume fraction (2.07+/-0.80 vs. 2.67+/-0.49, p<0.001) and nuclear
      hypertrophy (1.27+/-0.46 vs. 1.67+/-0.62, p<0.05). On the other hand,
      postoperative increase in myofibrillar volume fraction (1.87+/-0.61 vs. 1.40+/
      0.61, p<0.01) was noted. CONCLUSION: One year postoperatively, PLV has favourable
      effects on myocardial morphology that parallels improvement in the patient's
      functional status and LV systolic function.

PMID- 16087134
TI  - Sex and age differences in fragility in a heart failure population.
AB  - BACKGROUND: Heart failure (HF) patients have a high degree of fragility and
      dependence from physical, cognitive and psychological points of view, and are a
      mainly geriatric population. AIM: To detect the existence of fragility in all
      patients treated in a Heart Failure Unit and to evaluate age and sex differences.
      METHODS: All patients underwent a basic geriatric evaluation to detect possible
      loss of autonomy for doing basic and instrumental activities, cognitive
      deterioration, emotional disturbance or social risk. RESULTS: Three hundred sixty
      patients (mean age 65.2 years, 41.7% > or = 70 years, 27.5% women) were
      evaluated. Fragility was detected in 41.7% of patients, being more prevalent in
      patients > or = 70 years (p<0.001) and in women (p<0.001). A Barthel Index < 90
      was found in 22.5% of patients and an anomalous OARS Scale was found in 18.3%.
      Pfeiffer test's score was abnormal in 7.8% of patients. A positive depression
      response in abbreviate GDS was observed in 29.7%. All items analysed were more
      prevalent in patients > or = 70 years and in women, with the unexpected exception
      of depression symptoms that were as prevalent in younger as in older patients.
      CONCLUSION: Fragility is common in patients with heart failure, even in younger
      patients, and can be detected easily using standardised geriatric scales.
      Prevalence of fragility was significantly higher in older patients and in women,
      although the presence of depression symptoms was as prevalent in younger as in
      older patients.

PMID- 16087135
TI  - Transcardiac gradients of N-terminal B-type natriuretic peptide in aortic valve
      stenosis.
AB  - BACKGROUND: Plasma B-type natriuretic peptide (BNP), as well as the N-terminal
      part of the prohormone (Nt-BNP), are frequently elevated in aortic valve stenosis
      (AS). Yet, their release from the heart into the circulation has never been
      directly studied in AS. AIM: To assess the release of Nt-BNP in AS with focus on
      the identification of its main determinants. METHODS: We studied 49 adult
      patients undergoing preoperative cardiac catheterization for isolated AS. Blood
      was sampled from the aortic root and the coronary sinus for Nt-BNP determination
      by immunoassay. RESULTS: The mean (+/-S.E.) transcardiac Nt-BNP step-up averaged
      79+/-53 pmol/l in 11 control patients free of structural heart disease, 75+/-32
      pmol/l in 31 AS patients free of heart failure (HF), 236+/-62 pmol/l in 8 AS
      patients with diastolic HF (ejection fraction > or = 50%, pulmonary wedge
      pressure > 14 mm Hg) and 469+/-66 pmol/l in 7 AS patients with systolic HF
      (ejection fraction < 50%, wedge pressure > 14 mm Hg) (p<0.001). The transcardiac
      Nt-BNP gradient was independently associated with left ventricular (LV) end
      diastolic pressure (beta=0.47, p<0.001) and ejection fraction (beta=-0.29,
      p<0.019) and with co-existent coronary artery disease (beta=0.23, p=0.050).
      CONCLUSION: LV diastolic and systolic dysfunction along with coronary artery
      disease are likely to be the key determinants of cardiac Nt-BNP release in AS.
      The transcardiac Nt-BNP gradient increases on average three-fold with the
      development of diastolic HF and six-fold in systolic HF.

PMID- 16087136
TI  - Echocardiographic ejection fraction in patients with acute heart failure:
      correlations with hemodynamic, clinical, and neurohormonal measures and short
      term outcome.
AB  - BACKGROUND: Although echocardiographic ejection fraction (EF) is frequently used
      for the estimation of left ventricular contractility in patients with acute heart
      failure, its exact role and correlations with clinical, hemodynamic, and
      neurohormonal variables of cardiac contractility is not known. METHODS: Patients
      (343) with acute heart failure, enrolled into two prospective placebo-controlled
      hemodynamic studies of tezosentan, and in whom EF was available at baseline, were
      included. Outcome was evaluated in a subset of 94 patients who were enrolled in
      the placebo arms of the studies. RESULTS: Higher echocardiographic EF was
      correlated with older age, increased incidence of hypertension and atrial
      fibrillation, and female gender. We observed weak correlation between EF and
      cardiac output or cardiac power and no correlation with wedge pressure, and the
      change in hemodynamic variables over time. Higher EF was correlated with more
      baseline leukocytosis and higher plasma levels of endothelin-1 and blood urea
      nitrogen, while lower EF was related to higher baseline B-type natriuretic
      peptide (BNP). We observed no overall correlations between EF and outcome.
      CONCLUSIONS: In patients with acute heart failure, echocardiographic EF is weakly
      correlated with hemodynamic measures of left ventricular contractility and
      outcome; hence, it should be interpreted cautiously when evaluating patients
      admitted due to acute heart failure.

PMID- 16087137
TI  - Echocardiographic evaluation of left ventricular end-systolic elastance in the
      elderly.
AB  - BACKGROUND: The aging heart is characterized by structural changes, which are
      implicated in the development of left ventricular diastolic dysfunction. However,
      important changes in systolic function may also occur. Left ventricular end
      systolic elastance (E(es)) is a major determinant of cardiac systolic function
      and ventricular-arterial interaction. AIM: To evaluate left-ventricular E(es) in
      elderly subjects compared with adult control subjects. METHODS: We studied
      dilated (DA, n=14) and hypertensive (HA, n=21) cardiomyopathy patients, and both
      adult control (A, n=25; age 55.6+/-6.6 years) and elderly (E, n=25; age 76.3+/
      7.1 years) subjects without clinical-instrumental evidence of cardiovascular
      disease. M-mode, two-dimensional, and pulsed Doppler echocardiogram were
      performed. Doppler-derived indices of diastolic function were assessed and E(es)
      was calculated by a modified single-beat method. RESULTS: E(es) was reduced in
      dilated cardiomyopathy (1.32+/-0.10 mm Hg/ml) and increased in hypertensive
      cardiomyopathy (3.12+/-0.33 mm Hg/ml) patients compared to age-matched control
      subjects (1.96+/-0.26 mm Hg/ml; p<0.01 and p<0.05, respectively). More
      importantly, E(es) was higher in the elderly (2.52+/-0.70 mm Hg/ml) than in the
      adult control group (p<0.05) and was linearly correlated with age (r2=0.639;
      p<0.0001). CONCLUSION: Age-related increase in E(es), together with diastolic
      dysfunction, may lead to aging heart decompensation.

PMID- 16087138
TI  - The additive prognostic value of restrictive pattern and dipyridamole-induced
      contractile reserve in idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Diastolic dysfunction and lack of contractile reserve are unfavorable
      prognostic predictors in patients with dilated cardiomyopathy (DCM). AIMS: This
      study aims to assess whether diastolic dysfunction and lack of dipyridamole
      induced contractile reserve were additive predictors of poor outcome in patients
      with DCM. METHODS: A total of 116 patients with DCM and ejection fraction
      (EF<35%) were studied by dipyridamole echo (0.84 mg/kg over 10 min). At rest, a
      restrictive filling pattern was defined as: E/A ratio >2 and an E-wave
      deceleration time of <140 ms on transmitral flow velocity profile. RESULTS: Rest
      wall motion score index (WMSI) was 2.2+/-0.3 and decreased to 1.9+/-0.41 after
      dipyridamole (p<0.001). During follow-up (median 26.5 months), 22 cardiac deaths
      occurred. At multivariate analysis, dipyridamole-induced contractile reserve
      yielded significant incremental prognostic value (RR=0.275, p<0.006) over NYHA
      class (RR=1.971, p<0.03), angiotensin-converting enzyme inhibitor therapy
      (RR=0.173, p<0.001), and left ventricular end-diastolic diameter (RR=1.131,
      p<0.001). The worst prognostic combination was the presence of restrictive
      pattern at rest and the absence of contractile reserve (deltaWMSI<0.15).
      CONCLUSION: In patients with DCM, the ominous combination of restrictive
      transmitral flow pattern and lack of contractile reserve during dipyridamole
      stress predicts an unfavourable outcome.

PMID- 16087139
TI  - Cellular endotoxin desensitization in patients with severe chronic heart failure.
AB  - BACKGROUND: Increased levels of bacterial lipopolysaccharide (LPS) have been
      demonstrated in chronic heart failure (CHF). LPS can induce cellular
      desensitization, with specific down-regulation of LPS-mediated cellular tumor
      necrosis factor (TNF-alpha) production which does not affect other cytokine
      parameters. It is not known if LPS desensitization occurs in CHF. METHODS AND
      RESULTS: Mononuclear cells from 24 CHF patients (mean age 70+/-2 years, age range
      58 to 78 years, NYHA class 3.0+/-0.2) and 11 healthy controls (mean age 53+/-3
      years, age range 39 to 75 years) were separated from venous blood and cultured
      for 24 h with LPS (E. coli, 0-10 ng/mL). Culture supernatants were tested for TNF
      alpha and interleukin-1 receptor antagonist (IL-1RA). Patients were subgrouped
      into mild (n=10), moderate (n=5), and severe (n=9) CHF. Independently of age,
      mononuclear cells from patients with severe heart failure produced less TNF-alpha
      than controls (p<0.05) and patients with mild (p<0.001) or moderate CHF (p<0.05).
      IL-1RA release was higher for CHF patients as a group, compared with controls
      (p<0.05). There was no significant difference in IL-1RA release between CHF
      patient subgroups. CONCLUSIONS: Mononuclear cells from patients with severe heart
      failure produce significantly less TNF-alpha than healthy controls or patients
      with mild to moderate disease. Production of IL-1RA is not affected. This
      resembles a picture indicative of LPS desensitization occurring in patients with
      severe CHF.

PMID- 16087140
TI  - Vagal heart rate responses to chronic beta-blockade in human heart failure relate
      to cardiac norepinephrine spillover.
AB  - We have documented a pre-junctional beta-2 adrenoceptor mediated reduction in
      cardiac norepinephrine spillover (CNES) in heart failure patients receiving
      chronic beta-blockade. Our present objective was to ascertain the consequence of
      this decrease for vagal heart rate (HR) regulation by determining CNES, arterial
      baroreflex sensitivity for HR (BRS) and arterial baroreflex modulation of muscle
      sympathetic nerve activity (MSNA) before and upon 4 months of beta-blockade with
      either carvedilol or metoprolol. In 19 heart failure patients in sinus rhythm
      (age: 55+/-2 [mean+/-S.E.]; ejection fraction: 20+/-2%), beta-blockade increased
      BRS from 4.8+/-0.9 to 7.9+/-1.3 ms/mm Hg (P<0.005) but had no effect on arterial
      baroreflex modulation of MSNA. Changes in CNES and BRS were inversely related (r=
      0.52; n=16, P<0.05). Chronic beta-blockade in heart failure augments reflex vagal
      control of HR at an efferent site of interaction involving blockade of cardiac
      sympathetic pre-junctional beta-2 adrenoceptors that facilitate NE release.

PMID- 16087141
TI  - Clinical and neurohumoral consequences of diuretic withdrawal in patients with
      chronic, stabilized heart failure and systolic dysfunction.
AB  - BACKGROUND: Loop diuretics are beneficial in heart failure in the short term
      because they eliminate fluid retention, but in the long-term, they could
      adversely influence prognosis due to activation of neurohumoral mechanisms. AIMS:
      To explore the changes induced by diuretic withdrawal in chronic nonadvanced
      heart failure. METHODS: Diuretics were withdrawn in 26 stabilized heart failure
      patients with systolic dysfunction (ejection fraction [EF]<45%). Clinical status
      was evaluated by physical exam, exercise capacity (corridor test) and New York
      Heart Association (NYHA) class. Biochemical and neurohumoral determinations were
      performed at baseline and at 3 months. RESULTS: At 3 months, 17 out of 26
      patients (65%) were able to tolerate diuretic interruption without a
      deterioration in exercise capacity or New York Heart Association functional
      class. Renal function parameters improved (baseline urea 46.2+/-10.8 to 39.2+/
      10.1 mg/dl at 3 months, p=0.014; creatinine 1.1+/-0.23 to 0.98+/-0.2 mg/dl,
      p=0.013). Glucose metabolism also improved (fasting glucose 151+/-91 to 122+/-14
      mg/dl, p=0.035). Heart rate and systolic blood pressure did not significantly
      change, while diastolic blood pressure increased (from 80+/-10 to 87+/-13 mm Hg,
      p=0.006). Neurohumoral determinations showed a decrease in plasma renin activity
      (4.19+/-5.96 to 2.88+/-4.98 ng/ml, p=0.026), with no changes in aldosterone,
      arginine-vasopressin, endothelin-1 and norepinephrine. In contrast, atrial
      natriuretic peptide significantly increased (115+/-87 to 168+/-155 pg/ml,
      p=0.004). CONCLUSION: Diuretic withdrawal in stabilized heart failure with
      systolic dysfunction is associated with an improvement in renal function
      parameters, glucose metabolism and some neurohumoral parameters, such as plasma
      renin activity; however, atrial natriuretic peptide levels increased.

PMID- 16087142
TI  - Left ventricular systolic dysfunction, total mortality, and sudden death in
      patients with myocardial infarction treated with n-3 polyunsaturated fatty acids.
AB  - BACKGROUND: Sudden death (SD) has a major impact on mortality (M) in patients
      with left ventricular systolic dysfunction (SyD). In GISSI-Prevenzione, treatment
      with n-3 polyunsaturated fatty acids (PUFA) reduced M and SD in post-MI patients,
      but their effect in patients with SyD is unknown. METHODS: 11,323 patients with
      prior MI and NYHA class < or = II were recruited. After excluding patients with
      no ejection fraction (EF) measurement (1684), and those with missing data (n=9),
      9630 patients were available for analysis. Multivariate Cox regression adjusted
      models were fitted. RESULTS: Compared to patients with EF > 50%, SyD patients had
      higher M (12.3% vs. 6.0%) and SD (3.4% vs. 1.4%) rates. PUFA reduced M similarly
      in patients with (RR 0.76 (0.60-0.96) P=0.02) and without SyD (RR 0.81 (0.59
      1.10) P=0.17) (heterogeneity tests P=0.55). In contrast, the effect on SD was
      markedly asymmetrical: PUFA produced a marked reduction (RR 0.42 (0.26-0.67)
      P=0.0003) of risk in SyD patients whereas the effect was less evident (RR 0.89
      (0.41-1.69) P=0.71) in patients with EF > 50% (heterogeneity tests P=0.07). There
      was a significant increase in SD with worsening EF (P test for trend=0.02), the
      benefit on SD in patients with EF < or = 40% being 4-fold higher than in those
      with EF > 50%. CONCLUSIONS: Increasing SyD is associated with elevated risk of SD
      and with increasing benefit from PUFA. The effect of PUFA on SD reduction was
      greater in patients with SyD. Prospective trials testing the effect of PUFA in
      populations with SyD are required.

PMID- 16087143
TI  - Heart failure programmes in countries with a primary care-based health care
      system. Are additional trials necessary? Design of the DEAL-HF study.
AB  - BACKGROUND: Several randomised studies of heart failure (HF) management
      programmes in the United States, Australia and Europe have shown a considerable
      reduction in hospitalisation rates for HF. In this article, a comprehensive
      review of these studies will be provided and their applicability to countries,
      with a primary care-based healthcare system, will be discussed. In addition, the
      design of the Deventer-Alkmaar HF Project (DEAL-HF), a randomised study of the
      effect of a nurse and physician-directed intervention over 1 year in The
      Netherlands, will also be presented. AIM: To discuss the applicability of the
      results of available studies on heart failure management programmes to countries
      with well-structured primary care facilities and to determine whether additional
      trials should be conducted in these countries. METHODS: We performed a literature
      search in PubMed. In a review of the available studies, essential methodological
      aspects, in particular, the population involved, the sample size, follow-up
      period, setting, type of intervention, and the outcome parameters, are discussed
      critically. Also, the applicability of these studies to countries with a primary
      care-based healthcare system and easy access to medical care is evaluated.
      CONCLUSION: Applicability of the results of the available studies on the efficacy
      of heart failure management programmes to countries with a primary care-based
      health care system is doubtful. An efficacy trial in a country with a well
      established primary care-based healthcare system, such as The Netherlands, is due
      to report soon (DEAL-HF).

PMID- 16087144
TI  - Clinical trials update from the American College of Cardiology meeting: CARE-HF
      and the remission of heart failure, Women's Health Study, TNT, COMPASS-HF,
      VERITAS, CANPAP, PEECH and PREMIER.
AB  - This article provides information and a commentary on landmark trials presented
      at the American College of Cardiology meeting held in March 2005, relevant to the
      pathophysiology, prevention and treatment of heart failure. All reports should be
      considered as preliminary data, as analyses may change in the final publication.
      CARE-HF showed that Cardiac Re-synchronisation Therapy, administered in addition
      to expert pharmacological management, reduced all cause mortality and CV
      hospitalisation in patients with moderate or severe heart failure and cardiac
      dyssynchrony. The Women's Health Study showed no benefit of vitamin E
      supplementation or aspirin in the primary prevention of CV disease. The TNT study
      showed that reducing LDL cholesterol to levels lower than currently recommended,
      produced a 22% reduction in the incidence of major cardiovascular events. In
      COMPASS, an implantable device that continuously monitors intra-cardiac pressures
      was shown to be safe and to improve care in patients with chronic heart failure.
      Tezosentan failed to show benefit in patients with acute heart failure in the
      VERITAS study. The CANPAP study failed to show a benefit of continuous positive
      airway pressure on mortality and heart transplantation in heart failure patients
      with central sleep apnoea. EECP therapy improved exercise capacity but had no
      effect on peak VO2 in heart failure patients in the PEECH study. In the PREMIER
      study the matrix metalloproteinase inhibitor PG-116800 failed to prevent LV
      remodelling following myocardial infarction.

PMID- 16087145
TI  - Immune regulation of gammadelta T cell responses in mycobacterial infections.
AB  - Antigen-specific gammadelta T cells may play a role in anti-mycobacterial
      immunity. Studies done in humans and animal models have demonstrated complex
      patterns of gammadelta T cell immune responses during early mycobacterial
      infections and chronic tuberculosis. Recent studies have also shown a clinical
      correlation between major recall expansion of antigen-specific gammadelta T cells
      and immunity against fatal early mycobacterial diseases. Multiple host and
      microbial factors can regulate diverse immune responses of phosphoantigen
      specific gammadelta T cells during mycobacterial infections.

PMID- 16087146
TI  - Primary immunodeficiency diseases consortium conference.

PMID- 16087147
TI  - Coordination of cranial motoneurons during mastication.
AB  - Mastication is the first stage of digestion and involves several motor processes
      such as food intake, intra-oral food transport, bolus formation and chewing in
      its broad sense. These complicated motor functions can be accomplished by the
      well-coordinated activities in various cranial motoneurons innervating the jaw,
      hyoid, tongue and facial muscles. The brainstem masticatory central pattern
      generator (CPG) plays a crucial role in generating basic activity patterns of
      these cranial motoneuron groups. However, descending inputs from higher brain
      (e.g., cerebral cortex) and mastication-generated peripheral sensory inputs also
      play important roles in modulating the activity pattern of each motoneuron so
      that the final motor outputs fit the environmental demand. In this review, we
      focus on the coordination of the trigeminal, facial and hypoglossal motoneurons
      during mastication. We first summarize findings showing the activity patterns of
      muscles innervated by these motoneurons during natural mastication, and then
      discuss the possible neural mechanisms underlying their coordinated activities
      during mastication.

PMID- 16087148
TI  - Does episodic hypoxia affect upper airway dilator muscle function? Implications
      for the pathophysiology of obstructive sleep apnoea.
AB  - Obstructive sleep apnoea (OSA) is characterised by repetitive collapse of the
      upper airway during sleep owing to a sleep-related decrement in upper airway
      muscle activity with consequent failure of the pharyngeal dilator muscles to
      oppose the collapsing pressure that is generated by the diaphragm and accessory
      muscles during inspiration. The causes of upper airway obstruction during sleep
      are multi-factorial but there is evidence implicating intrinsic upper airway
      muscle function and impaired central regulation of the upper airway muscles in
      the pathophysiology of OSA. The condition is associated with episodic hypoxia due
      to recurrent apnoea. However, despite its obvious importance very little is known
      about the effects of episodic hypoxia on upper airway muscle function. In this
      review, we examine the evidence that chronic intermittent hypoxia can affect
      upper airway muscle structure and function and impair CNS control of the
      pharyngeal dilator muscles. We review the literature and discuss results from our
      laboratory showing that episodic hypoxia/asphyxia reduces upper airway muscle
      endurance and selectively impairs pharyngeal dilator EMG responses to
      physiological stimulation. Our observations lead us to speculate that episodic
      hypoxia--a consequence of periodic airway occlusion--is responsible for
      progression of OSA through impairment of the neural control systems that regulate
      upper airway patency and through altered respiratory muscle contractile function,
      leading to the establishment of a vicious cycle of further airway obstruction and
      hypoxic insult that chronically exacerbates and perpetuates the condition. We
      conclude that chronic intermittent hypoxia/asphyxia contributes to the
      pathophysiology of sleep-disordered breathing.

PMID- 16087149
TI  - Phenotype and contractile properties of mammalian tongue muscles innervated by
      the hypoglossal nerve.
AB  - The XIIth cranial nerve plays a role in chewing, respiration, suckling,
      swallowing, and speech [Lowe, A.A., 1981. The neural regulation of tongue
      movements. Prog. Neurobiol. 15, 295-344.]. The muscles innervated by this nerve
      are functionally subdivided into three categories: those causing protrusion,
      retrusion, and changing the shape of the tongue. Myosin heavy chain (MHC) II
      isoform makes up the majority of the MHC phenotype with some variability among
      mammalian species and some evidence suggests between genders. In addition, there
      are regional differences in fiber type within some of these muscles that suggest
      functional compartmentalization. The transition from developmental MHC isoforms
      to their adult phenotype appears to vary not only from muscle to muscle but also
      from species to species. Motor units within this hypoglossal motor system can be
      categorized as predominantly fast fatigue resistant. Based on twitch contraction
      time and fatigue index, it appears that hypoglossal innervated muscles are more
      similar to fast-twitch muscles innervated by spinal nerves than, for example,
      extraocular muscles.

PMID- 16087150
TI  - Purification and kinetic characterization of recombinant human mitogen-activated
      protein kinase kinase kinase COT and the complexes with its cellular partner NF
      kappa B1 p105.
AB  - Cancer osaka thyroid (COT), a human MAP 3 K, is essential for lipopolysaccharide
      activation of the Erk MAPK cascade in macrophages. COT 30--467 is insoluble,
      whereas low levels of COT 30--397 can be expressed, but this protein is unstable.
      However, both COT 30--467 and COT 30--397 are expressed in a soluble and stable
      form when produced in complex with the C-terminal half of p105. The k(cat) of COT
      30--397 is reduced approximately 47--fold in the COT 30--467/p105 Delta N
      complex. COT prefers Mn(2+) to Mg(2+) as the ATP metal cofactor, exhibiting an
      unusually high ATP K(m) in the presence of Mg(2+). When using Mn(2+) as the
      cofactor, the ATP K(m) is reduced to a level typical of most kinases. In
      contrast, the binding affinity of COT for its other substrate MEK is cofactor
      independent. Our results using purified proteins indicate that p105 binding
      improves COT solubility and stability while down-regulating kinase activity,
      consistent with cellular data showing that p105 functions as an inhibitor of COT.

PMID- 16087151
TI  - Evaluation of radioprotective effect of vitamin E in salivary dysfunction in
      irradiated rats.
AB  - The aim of this study was to evaluate the radioprotective effect of vitamin E in
      salivary gland function, as well as analyse the total protein concentration. For
      this purpose 90 male rats were used and randomly divided into five experimental
      groups: control (I), in which animals received olive oil solution but were not
      irradiated; irradiated-olive oil (II), in which animals received olive oil
      solution and were irradiated with a single exposure dose of 15 Gy of gamma rays
      to the head and neck region; irradiated (III), in which animals were only
      irradiated with a single exposure dose of 15 Gy of gamma rays; vitamin E (IV), in
      which animals received alpha tocopherol acetate solution but were not irradiated;
      irradiated-vitamin E (V), in which animals received alpha tocopherol acetate
      solution before irradiation with a single exposure dose of 15 Gy gamma rays. The
      animals were sacrificed 4, 8 h and 30 days after the irradiation procedure. No
      differences were observed in salivary volumes between the groups at 4 and 8 h. At
      30 days, the salivary volume in the animals pertaining to the irradiated-olive
      oil group was significantly reduced in relation to the control group. The only
      irradiated group (III) presented significantly diminished salivary volume. In the
      salivary composition, no significant differences were observed in the total
      protein content between the groups studied. It was concluded that radiation had
      no effect on the total protein content and that vitamin E protected the salivary
      function 30 days after irradiation. Thus, vitamin E can be considered as a
      potential radioprotective substance.

PMID- 16087152
TI  - N-acyl phosphatidylethanolamines affect the lateral distribution of cholesterol
      in membranes.
AB  - N-Acyl phosphatidylethanolamines are negatively charged phospholipids, which are
      naturally occurring albeit at low abundance. In this study, we have examined how
      the amide-linked acyl chain affected the membrane behavior of the N-acyl-1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine (N-acyl-POPE) or N-acyl
      dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (N-acyl-DPPE), and how the
      molecules interacted with cholesterol. The gel-->liquid crystalline transition
      temperature of sonicated N-acyl phosphatidylethanolamine vesicles in water
      correlated positively with the number of palmitic acyl chains in the molecules.
      Based on diphenylhexatriene steady state anisotropy measurements, the presence of
      33 mol% cholesterol in the membranes removed the phase transition from N-oleoyl
      POPE bilayers, but failed to completely remove it from N-palmitoyl-DPPE and N
      palmitoyl-POPE bilayers, suggesting rather weak interaction of cholesterol with
      the N-saturated NAPEs. The rate of cholesterol desorption from mixed monolayers
      containing N-palmitoyl-DPPE and cholesterol (1:1 molar ratio) was much higher
      compared to cholesterol/DPPE binary monolayers, suggesting a weak cholesterol
      interaction with N-palmitoyl-DPPE also in monolayers. In bilayer membranes, both
      N-palmitoyl-POPE and N-palmitoyl-DPPE failed to form sterol-rich domains, and in
      fact appeared to displace sterol from sterol/N-palmitoyl-sphingomyelin domains.
      The present data provide new information about the effects of saturated NAPEs on
      the lateral distribution of cholesterol in NAPE-containing membranes. These
      findings may be of relevance to neural cells which accumulate NAPEs during stress
      and cell injury.

PMID- 16087153
TI  - Nateglinide uptake by a ceftibuten transporter in the rat kidney brush-border
      membrane.
AB  - Nateglinide, a novel oral hypoglycemic agent, possesses a carbonyl group and a
      peptide-type bond in its structure. We previously reported that nateglinide
      transport occurs via a single system that may be identical to the ceftibuten/H(+)
      cotransport system by the rat small intestine. We speculated that the absorption
      system present on the intestinal epithelium may be similar to that found on the
      renal tubular epithelium. The aim of this study was to characterize the
      transporters on the apical side of the kidney that may contribute to the
      reabsorption of ceftibuten and nateglinide. The uptake of nateglinide by rat
      renal brush-border membranes is associated with an H(+)-coupled transport system.
      Ceftibuten competitively inhibited H(+)-dependent nateglinide uptake. In
      contrast, Gly-Sar, cephradine and cephalexin had no effect on nateglinide uptake.
      Nateglinide competitively inhibited H(+)-driven transporter-mediated ceftibuten
      uptake. We conclude that nateglinide transport occurs via a single system that is
      H(+)-dependent and may be identical to the ceftibuten/H(+) cotransport system.

PMID- 16087154
TI  - Cognitive inhibition and interference in dissociative identity disorder: the
      effects of anxiety on specific executive functions.
AB  - Using an experimentally based, computer-presented task, this study assessed
      cognitive inhibition and interference in individuals from the dissociative
      identity disorder (DID; n=12), generalized anxiety disorder (GAD; n=12) and non
      clinical (n=12) populations. Participants were assessed in a neutral and
      emotionally negative (anxiety provoking) context, manipulated by experimental
      instructions and word stimuli. The DID sample displayed effective cognitive
      inhibition in the neutral but not the anxious context. The GAD sample displayed
      the opposite findings. However, the interaction between group and context failed
      to reach significance. There was no indication of an attentional bias to non
      schema specific negative words in any sample. Results are discussed in terms of
      the potential benefit of weakened cognitive inhibition during anxious arousal in
      dissociative individuals.

PMID- 16087155
TI  - Dysfunctional beliefs in panic disorder: The Panic Belief Inventory.
AB  - The Panic Belief Inventory (PBI) was developed to assess beliefs that increase
      the likelihood of catastrophic reactions to physical and emotional experiences in
      panic disorder. In the first stage of scale development, 197 panic disorder
      patients completed the PBI and standard self-report inventories of psychiatric
      symptomatology. An exploratory factor analysis yielded a 4-factor solution from
      which a 35-item instrument with 4 scales was constructed. The shortened measure
      and its scales had good internal consistency and convergent validity and moderate
      discriminant validity. Subsequently, 22 panic disorder patients who received
      cognitive therapy completed the PBI and other self-report inventories of
      dysfunctional cognitions at intake, 4 weeks, 8 weeks, termination, and several
      follow-up intervals. Results indicated that the PBI decreased significantly
      across treatment, with the largest decline occurring between intake and 4 weeks
      into treatment. The PBI correlated more strongly with dysfunctional cognitions
      associated with anxiety than dysfunctional cognitions associated with depression.
      These results provide preliminary evidence that the PBI has adequate psychometric
      characteristics, is useful to assess change in dysfunctional beliefs during
      treatment, and has the potential to advance cognitive theories of panic.

PMID- 16087156
TI  - Knockdown of p53 by RNAi in ES cells facilitates RA-induced differentiation into
      muscle cells.
AB  - The p53 gene is widely expressed in embryo, tissues, and tumors, and its
      deficiency can rescue embryonic defects in certain genes null embryos. However,
      it is still poorly understood whether p53 is involved in myoblast and neuronal
      fate determination during embryogenesis. We established the ES cell clone in
      which p53 protein was persistently suppressed by stable expression of p53 RNAi,
      and GFP was expressed in a p53 RNAi transcription-independent manner. With the
      classical protocol in which the differentiation of ES cells into either neural or
      muscle cell is specifically modulated by different dosage retinoic acid (RA), we
      evaluated the function of p53 during myoblast and neuronal commitment. With RA
      treatment, silencing of p53 by RNAi in ES cells leads to dominant muscle cell
      production but lack of neuronal cell, indicating that p53 indeed plays a role
      during muscle and neuronal fate commitment. It thus provides a good model for
      investigating cross-talk between RA and p53 pathways during myogenesis and
      neurogenesis from ES cells.

PMID- 16087157
TI  - Dual effects of adenovirus-mediated thrombopoietin gene transfer on hepatic oval
      cell proliferation and platelet counts.
AB  - Thrombopoietin (TPO) is the growth factor for megakaryocytes and platelets,
      however, it also acts as a potent regulator of stem cell proliferation. To
      examine the significance of TPO expression in proliferation of hepatic oval
      cells, the effect of adenovirus-mediated TPO gene transfer into livers of the
      Solt-Farber model, which mimics the condition where liver regeneration is
      impaired, was examined. Hepatic TPO mRNA peaked its expression at 2 days after
      gene transduction and then gradually decreased. The peripheral platelet number
      began to increase at 4 days (P<0.05) and reached its plateau at 9 days (P<0.01).
      Oval cells expressed c-Mpl, a receptor for TPO as well as immature hematopoietic
      and hepatocytic surface markers such as CD34 and AFP. The proliferating cell
      nuclear antigen-positive oval cells in rats into which adenovirus-TPO gene was
      transferred at 7 and 9 days were significantly greater than those in adenovirus
      LacZ gene transferred (P<0.05, each), and the total numbers of oval cells in the
      adenovirus-TPO gene transferred at 9 and 13 days were also significantly greater
      than those in adenovirus-LacZ gene transferred (P<0.05, each). Expression of SCF
      protein was increased at 4, 7, and 9 days by TPO gene administration and that of
      c-Kit was increased at 4 and 7 days. These data suggest that adenovirus-mediated
      TPO gene transfer stimulated oval cell proliferation in liver as well as
      increasing peripheral platelet counts, emphasizing the significance of the TPO/c
      Mpl system in proliferation of hepatic oval cells.

PMID- 16087158
TI  - Single amino acid substitutions in the C-terminus of collagen II alter its
      affinity for collagen IX.
AB  - The structural integrity of cartilage depends on the presence of extracellular
      matrices (ECM) formed by heterotypic fibrils composed of collagen II, collagen
      IX, and collagen XI. The formation of these fibrils depends on the site-specific
      binding between relatively small regions of interacting collagen molecules.
      Single amino acid substitutions in collagen II change the physicochemical and
      structural characteristics of those sites, thereby leading to an alteration of
      intermolecular collagen II/collagen IX interaction. Employing a biosensor to
      study interactions between R75C, R789C or G853E collagen II mutants and collagen
      IX, we demonstrated significant changes in the binding affinities. Moreover,
      analyses of computer models representing mutation sites defined exact changes in
      physicochemical characteristics of collagen II mutants. Our study shows that
      changes in collagen II/collagen IX affinity could represent one of the steps in a
      cascade of changes occurring in the ECM of cartilage as a result of single amino
      acid substitutions in collagen II.

PMID- 16087159
TI  - Cardiopulmonary bypass reduces atrial Na+-K+-ATPase expression in children.
AB  - Cardiopulmonary bypass (CPB) may induce serious side effects, potentially leading
      to myocardial failure. The Na(+)-K(+)-ATPase is a key component for myocardial
      function. Due to its developmental regulation, results from adult studies cannot
      be adopted to the situation in childhood. Right atrial myocardium from patients
      with left-to-right shunts at atrial level (VO, n=8) and those without (NO, n=8)
      was excised during heart surgery before and after CPB. Na(+)-K(+)-ATPase isoforms
      ATP1A1 (p=0.008) and ATP1A3 (p=0.038) decreased during CPB, which decrease was
      restricted to the VO group. This study highlights the importance of the
      underlying heart defect for susceptibility to the effects of CPB, showing a
      reduced Na(+)-K(+)-ATPase mRNA expression only in patients with left-to-right
      shunts on the atrial level. This seemed to be an early molecular event, as apart
      from one, none of the patients showed heart failure before or after surgery.

PMID- 16087160
TI  - The human prothrombin kringle-2 derived peptide, NSA9, is internalized into
      bovine capillary endothelial cells through endocytosis and energy-dependent
      pathways.
AB  - Human prothrombin kringle-2 and its partial peptide, NSA9 (NSAVQLVEN), have been
      reported to have potent anti-angiogenic activities. Here, the internalization
      mechanism of NSA9 into bovine capillary endothelial (BCE) cells was examined
      using lactate dehydrogenase (LDH) release assay, fluorescence microscopy, and
      flow cytometry. LDH release assay results suggested that the integrity of the BCE
      cell membrane was unaffected by NSA9. Fluorescence microscopy indicated that
      internalized NSA9 was localized in the cytoplasm around the nucleus, and showed a
      punctuated fluorescence pattern, which is indicative of endocytic vesicles. Also,
      the cellular internalization of NSA9 is significantly inhibited by depletion of
      the cellular ATP pool, endocytosis inhibitors such as chloroquine and nocodazole,
      and incubation at low temperature (4 degrees C). In addition, the anti
      proliferative activity of NSA9 against BCE cells was diminished in the presence
      of endocytosis or metabolic inhibitors. In conclusion, these results strongly
      suggest that NSA9 might exert its anti-proliferative activity through
      internalization into BCE cells by endocytosis and energy-dependent pathways.

PMID- 16087161
TI  - Adenovirus-mediated hepatocyte nuclear factor-4alpha overexpression maintains
      liver phenotype in cultured rat hepatocytes.
AB  - Hepatocyte nuclear factor 4alpha (HNF-4alpha) is a transcription factor that
      controls embryonal liver development and that maintains and regulates gene
      expression in adult liver cells. We have previously demonstrated that transient
      overexpression of HNF-4alpha up-regulates a number of liver-specific genes in
      hepatoma cell lines. In this study, we extend these studies by assessing the
      functional role of HNF-4alpha in regulating cellular viability and liver-specific
      functions of primary rat hepatocytes. In cells transfected with an adenovirus
      vector carrying rat HNF-4alpha cDNA, induction and maintenance of liver-specific
      genes and functions were observed over a long-term culture, which might be
      associated with the prevention of a rapid loss of the mitochondrial membrane
      potential. In addition, we demonstrated that transthyretin mRNA was up-regulated
      by HNF-4alpha in primary hepatocytes, but not in hepatoma cells. These results
      indicate that HNF-4alpha plays a role in the maintenance of morphologically and
      biochemically functional hepatocytes and that the difference in expression of
      liver-specific genes induced by HNF-4alpha may depend on a differentiation state
      of cells.

PMID- 16087162
TI  - dsRNA-mediated innate immunity of epidermal keratinocytes.
AB  - MIP-1alpha, a CC chemokine, recruits monocytes, natural killer cells,
      lymphocytes, and neutrophils, and plays a critical role in viral infection.
      Since, the lesional epidermis of herpes zoster expressed MIP-1alpha, we
      hypothesized that keratinocytes produce MIP-1alpha in response to virus
      associated dsRNA via TLR3. To investigate this, we examined cultured human
      keratinocytes for MIP-1alpha production induced by poly(I:C), a TLR3 ligand.
      Poly(I:C) treatment induced MIP-1alpha production, interestingly, poly(I:C)
      induced IFN-alpha and -beta production preceded MIP-1alpha production. A
      neutralizing antibody for IFN-beta significantly inhibited the poly(I:C)-induced
      MIP-1alpha production indicating that MIP-1alpha production is via IFN-beta. IFN
      alpha priming enhanced TLR3 expression and MIP-1alpha production in poly(I:C)
      treated keratinocytes. This suggests that IFN-alpha enhanced the TLR3 expression
      and reinforced the response of keratinocytes to poly(I:C), which resulted in an
      increase in MIP-1alpha production. In conclusion, normal human keratinocytes
      produce MIP-1alpha in response to dsRNA via TLR3, and this production is
      regulated by IFN-alpha/beta.

PMID- 16087163
TI  - A genetic variant in the gene encoding the stress70 protein chaperone family
      member STCH is associated with gastric cancer in the Japanese population.
AB  - Association analysis, based on linkage disequilibrium between specific alleles in
      the candidate loci and nearby genetic markers, has been proposed to identify
      genes conferring susceptibility to multifactorial diseases. Using the affected
      sib-pair method, we previously mapped four candidate chromosomal regions, 1p32,
      2q33-q35, 11p13-p14, and 21q21, for gastric cancer by linkage analysis. To
      identify genes involved in the disease, we performed a gene-based association
      analysis of 66 genes, located on 21p11-21q22, using 126 single nucleotide
      polymorphisms (SNPs) as genetic markers in 373 patients with 250 controls. We
      found a significant association of five SNPs in the stress70 protein chaperon
      family member STCH gene with gastric cancer, especially with the non-cardia
      localization subgroup (P=0.0005-0.02, odds ratio=1.44-1.72). Comparisons of
      haplotype frequency showed significant association between TTGGC haplotype and
      gastric cancer (P=0.0001, odds ratio=1.59). These results suggest that, in the
      Japanese population, STCH might be a new candidate for conferring susceptibility
      to this disease.

PMID- 16087164
TI  - Resistin SNP-420 determines its monocyte mRNA and serum levels inducing type 2
      diabetes.
AB  - Resistin, secreted from adipocytes, causes insulin resistance in rodents. Its
      roles and main source in humans remain unknown. The G/G genotype of resistin
      single nucleotide polymorphism, SNP-420, induces type 2 diabetes mellitus (T2DM)
      by increasing promoter activity. We elucidated factors correlated with serum
      resistin and effects of SNP-420 on monocyte resistin mRNA. In 198 T2DM and 157
      controls, fasting serum resistin was higher in T2DM. Multiple regression analysis
      revealed that SNP-420 genotype was the strongest determinant of serum resistin.
      In T2DM, 1-year duration of T2DM and 1% HbA1c was also correlated with 0.19 and
      0.54 ng/ml serum resistin, respectively. Logistic regression analysis revealed
      that serum resistin was an independent factor for T2DM. In 23 healthy volunteers,
      monocyte resistin mRNA was positively correlated with its simultaneous serum
      levels and was higher in G/G genotype. Thus, SNP-420 determines monocyte mRNA and
      serum levels of resistin, which could induce T2DM.

PMID- 16087165
TI  - Very low-density lipoprotein induces interleukin-1beta expression in macrophages.
AB  - Elevated plasma level of very low-density lipoprotein (VLDL) is a risk factor for
      coronary heart disease. We investigated the effect of VLDL on expression of the
      pro-inflammatory cytokine interleukin-1beta (IL-1beta) in human peripheral blood
      monocyte-derived macrophages. IL-1beta mRNA and protein expression was analysed
      by PCR and ELISA, respectively. Caspase activation was assessed by
      immunoblotting. Apart from potentiating lipopolysaccharide-induced secretion of
      IL-1beta, VLDL alone induced secretion of IL-1beta from human monocyte-derived
      macrophages. This effect was suppressed by an inhibitor of caspase-1, the
      protease which cleaves pro-IL-1beta. VLDL treatment activated caspase-1, as
      indicated by increased levels of the caspase-1 p20 subunit. Furthermore, VLDL
      increased IL-1beta mRNA expression, which was associated with activation of
      transcription factor AP-1. Inhibition of caspase-1 did not influence IL-1beta
      mRNA expression. In conclusion, VLDL induces IL-1beta mRNA expression, caspase-1
      activation, and IL-1beta release from macrophages, suggesting that VLDL can
      promote inflammation in atherosclerotic lesions.

PMID- 16087166
TI  - Propagation of low calcium non-synaptic induced epileptiform activity to the
      contralateral hippocampus in vivo.
AB  - Recent experiments show that non-synaptic epileptiform activity can be induced by
      high K+ and low Ca2+ solution in vivo in the hippocampal CA1 region when synaptic
      transmission is blocked. However, the ability of this type of epileptiform
      activity to propagate to other brain areas is unknown. Presumably, this
      epileptiform activity should propagate and project along the axons to remote
      brain areas. This hypothesis was tested in vivo by inducing non-synaptic seizures
      in the left hippocampus and by recording spontaneous and evoked field potentials
      in both left and right hippocampi. The results show that one type of non-synaptic
      epileptiform activity, late bursts, observed in the left exposed CA1 and CA3
      regions could propagate to the contralateral intact CA1 and induce seizures with
      onsets of high-frequency rhythm. A cut of the commissural fibers near the midline
      of the brain prevented this propagation. In addition, the measurement of time
      delays between the exposed left CA3 and contralateral right CA1, as well as
      between the two recording electrodes in the right CA1, showed that the burst
      activity propagated through the commissural pathways. Experimental data also
      showed that these late bursts in the left hippocampus were first generated in the
      Schaffer collaterals of the CA1 region, traveled to the ipsilateral CA3 region
      and then propagated through the commissural fibers to the other side. These
      results suggest that non-synaptic epileptiform activity can propagate along axon
      projections to intact brain area causing seizure activity. This non-synaptic
      activity propagating through axonal pathway provides a possible mechanism for the
      generation of high-frequency low-amplitude onset activity observed commonly in
      human epileptic EEGs.

PMID- 16087167
TI  - Involvement of reticular neurons located dorsal to the facial nucleus in
      activation of the jaw-closing muscle in rats.
AB  - The location of excitatory premotor neurons for jaw-closing motoneurons was
      examined by the use of electrical and chemical stimulation and extracellular
      single-unit recording techniques in the anesthetized rat. Single-pulse electrical
      stimulation of the supratrigeminal region (SupV) and the reticular formation
      dorsal to the facial nucleus (RdVII) elicited masseter EMG response at mean (+/
      SD) latencies of 2.22 +/- 0.59 ms and 3.10 +/- 1.14 ms, respectively.
      Microinjection (0.1-0.3 microl) of glutamate (50 mM) or kainate (0.5-100 microM)
      into RdVII increased masseter nerve activity in artificially ventilated and
      immobilized rats by 30.2 +/- 40.5% and 50.7 +/- 46.8% compared to baseline
      values, respectively. Forty reticular neurons were antidromically activated by
      stimulation of the ipsilateral trigeminal motor nucleus (MoV). Twenty neurons
      were found in RdVII, and the remaining 20 neurons were located in SupV, or areas
      adjacent to SupV or RdVII. Eleven neurons in RdVII responded to at least either
      passive jaw opening or light pressure applied to the teeth or tongue. Nine
      neurons responded to passive jaw opening. Five of the nine neurons responded to
      multiple stimulus categories. A monosynaptic excitatory projection from one
      neuron in RdVII was detected by spike-triggered averaging of the rectified
      masseter nerve activity. We suggest that reticular neurons in RdVII are involved
      in increasing masseter muscle activity and that excitatory premotor neurons for
      masseter motoneurons are likely located in this area. RdVII could be an important
      candidate for controlling activity of jaw-closing muscles via peripheral inputs.

PMID- 16087168
TI  - Plasma free amino acids and their metabolites in Taiwanese patients on
      hemodialysis and continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND: The high prevalence of protein-energy malnutrition is a critical
      issue for patients with end stage renal disease (ESRD) on hemodialysis (HD) or
      continuous ambulatory peritoneal dialysis (CAPD). Levels of plasma and
      intracellular amino acids are significant indicators of protein metabolism and
      nutritional status assessment. We measured plasma FAAs in patients on maintenance
      dialysis and to provide information in monitoring the therapeutic strategy,
      particularly in AA supplementary therapy or protein restriction. METHODS: Fifty
      five patients with ESRD were investigated, 25 on HD (male : female=14 : 11; 48-67
      y) and 30 on CAPD (male : female=17 : 13; 45-64 y). The subjects had been on
      dialysis for an average of 13 months (range, 9 to 22 months). Their plasma FAAs
      (including their intermediate metabolites) were measured by ion exchange
      chromatography before and after HD or during CAPD and were compared with data
      obtained from 20 age- and sex-matched healthy controls. RESULTS: The total plasma
      FAA levels (urea and free ammonia, NH3 were excluded) in pre-HD samples (3911 +/-
      709 micromol/l) was significantly higher than in the other groups (2570 +/- 378
      in control, 3210 +/- 640 in post-HD, and 3468 +/- 271 in CAPD samples). The mean
      plasma FAA concentrations differed significantly between pre-HD and controls and
      between pre-HD and CAPD samples (p<0.05). No significant differences were found
      among the other group comparisons. Comparing individual FAA concentrations, only
      citrulline differed significantly among all groups (p<0.05), whereas serine,
      glutamine, beta-alanine, beta-aminoisobutyric acid, and gamma-aminobutyric acid
      were not different. Concentrations of some FAAs involved in the urea cycle, e.g.,
      arginine, aspartic acid, citrulline, and ornithines, and solutes urea and NH3,
      were significantly increased. Ratios of tyrosine/phenylalanine and valine/glycine
      ratios were markedly reduced in all patients on dialysis compared with controls.
      CONCLUSION: FAAs either from dietary uptake or protein catabolism are
      substantially retained in the plasma of patients with ESRD, possibly producing
      higher levels of the waste products (urea and NH3) through the urea cycle and
      ammonia metabolism in liver. Maintenance dialysis can effectively eliminate
      excess FAAs in plasma, as there was a 17.9% reduction post-HD. The abnormalities
      in FAA metabolism found in patients with ESRD necessitate careful consideration
      of dialysis and dietary measures.

PMID- 16087169
TI  - The diagnostic accuracy of carbohydrate-deficient transferrin, sialic acid and
      commonly used markers of alcohol abuse during abstinence.
AB  - BACKGROUND: The normalization of alcohol abuse markers during the abstinence
      depends on the time since the last drinking. The aim of this study was to
      evaluate the diagnostic accuracy (area under the curve-AUC, sensitivity and
      specificity) of CDT, sialic acid and others biochemical and hematological markers
      of chronic alcohol abuse during abstinence. METHODS: We studied 75 patients
      admitted to the treatment of alcohol dependence. The blood samples were collected
      upon admission to the hospital. CDT was estimated using an immunoturbidimetric
      assay after anion-exchange chromatography and sialic acid by enzymatic
      colorimetric method. RESULTS: Mean values of all markers were significantly
      higher. All tests, except SA, negatively correlated with time of abstinence but
      not with age, duration of dependence and amounts of weekly alcohol consumption.
      The area under the curve (AUC) for all tested markers decreased progressively
      during the abstinence. The highest AUC was obtained for CDT (0.98) and the lowest
      for ALT (0.78) when alcohol was consumed in the last week. AUC for sialic acid
      was lower than of CDT but higher than of ALT. CONCLUSIONS: We conclude that the
      diagnostic accuracy for tested laboratory markers depends on the self-reported
      time of abstinence being the highest for CDT in the first week of abstinence. The
      accuracy of sialic acid was observed between GGT and ALT.

PMID- 16087170
TI  - Competence and performance in belief-desire reasoning across two cultures: the
      truth, the whole truth and nothing but the truth about false belief?
AB  - There is a change in false belief task performance across the 3-5 year age range,
      as confirmed in a recent meta-analysis [Wellman, H. M., Cross, D., & Watson, J.
      (2001). Meta-analysis of theory mind development: The truth about false-belief.
      Child Development, 72, 655-684]. This meta-analysis identified several
      performance factors influencing success, including manipulations that highlight
      the salience of the initial belief content (such as asking where Sally will look
      first for the marble). However, because a proportion of variance in performance
      remained unexplained even when identified performance factors were controlled
      for, the authors concluded from the standpoint of a 'theory-theory' account that
      children's improvement is the result of conceptual change. Further, the meta
      analysis showed that manipulations such as 'look first' improve performance only
      in children who are in the older part of the 3-5 year range, and thus plausibly
      operating with a 'transitional' theory of mind--just on the point of realizing
      conceptual change. Here, we present three studies systematically investigating
      the 'look first' manipulation which showed that: (i) the advantage for the look
      first question can be demonstrated in children across different cultures, (ii)
      look first has an effect that is additive to the improvement with age; there is
      no interaction such that older children gain more benefit from younger children,
      (iii) performance in younger children can be, but is not always, elevated to
      levels that are statistically above chance. These results challenge the theory
      theory account and are discussed in terms of models of belief-desire reasoning in
      which both conceptual competence and performance factors play central roles.

PMID- 16087171
TI  - Identification, situational constraint, and social cognition: studies in the
      attribution of moral responsibility.
AB  - In three experiments we studied lay observers' attributions of responsibility for
      an antisocial act (homicide). We systematically varied both the degree to which
      the action was coerced by external circumstances and the degree to which the
      actor endorsed and accepted ownership of the act, a psychological state that
      philosophers have termed "identification." Our findings with respect to
      identification were highly consistent. The more an actor was identified with an
      action, the more likely observers were to assign responsibility to the actor,
      even when the action was performed under constraints so powerful that no other
      behavioral option was available. Our findings indicate that social cognition
      involving assignment of responsibility for an action is a more complex process
      than previous research has indicated. It would appear that laypersons' judgments
      of moral responsibility may, in some circumstances, accord with philosophical
      views in which freedom and determinism are regarded to be compatible.

PMID- 16087172
TI  - Differences in regulation of the first two M-phases in Xenopus laevis embryo cell
      free extracts.
AB  - The first embryonic M-phase is special, being the time when paternal and maternal
      chromosomes mix together for the first time. Reports from a variety of species
      suggest that the regulation of first M-phase has many particularities; however,
      no systematic comparative study of the biochemical aspects of first and the
      following M-phases has been previously undertaken. Here, we ask whether the
      regulation of the first embryonic M-phase is modified, using Xenopus cell-free
      extracts. We developed new types of extract specific for the first and the second
      M-phase obtained either from parthenogenetic or from in vitro fertilized embryos.
      Analyses of these extracts confirmed that the amplitude of histone H1 kinase
      activity reflecting CDK1/cyclin B (or MPF for M-phase Promoting Factor) activity
      is higher and persists longer than during the second M-phase, and that levels of
      cyclins B1 and B2 are correspondingly higher during the first than the second
      embryonic M-phase. Inhibition of protein synthesis shortly before M-phase entry
      reduced mitotic histone H1 kinase amplitude, shortened the period of mitotic
      phosphorylation of chosen marker proteins, and reduced cyclin B1 and B2 levels,
      suggesting a role of B-type cyclins in regulating the duration of mitotic events.
      Moreover, addition of exogenous cyclin B to the extract prior the second mitosis
      brought forward the activation of mitotic histone H1 kinase but prolonged the
      duration of this activity. We also confirmed that the inhibitory phosphorylation
      of CDK1 on tyrosine 15 oscillates between the first two embryonic M-phases, but
      is clearly more pronounced before the first than the second mitosis, while the
      MAP kinase ERK2 tended to show greater activation during the first embryonic M
      phase but with a similar duration of activation. We conclude that discrete
      differences exist between the first two M-phases in Xenopus embryo and that
      higher CDK1/cyclin B activity and B-type cyclin levels could account for the
      different characteristics of these M-phases.

PMID- 16087173
TI  - Cytoplasmic retention of the sex-determining factor SOX9 via the microtubule
      network.
AB  - SOX9 is a sex-determining factor which induces Sertoli cell differentiation and
      subsequent testis cord formation. It is expressed both in male and female
      undifferentiated gonads in the cytoplasmic compartment of pre-Sertoli cells. At
      the time of sexual differentiation, SOX9 moves into the nucleus of male pre
      Sertoli cells whereas in female, it remains in the cytoplasm and then its
      expression decreases. To study the cytoplasmic localization of SOX9, we have
      analyzed its interaction with the cytoskeleton components. By treatment of NT2/D1
      and transfected NIH3T3 cell lines and embryonic gonads with nocodazole, a drug
      depolymerizing the microtubules, we show that cytoplasmic retention of SOX9
      requires the integrity of the microtubule network. Using biochemical experiments,
      we demonstrated that SOX9 is able to interact with microtubules in vitro and in
      vivo. On the other hand, we observed a complete male-specific reorganization of
      the microtubule network in epithelial Sertoli cells of the male embryonic gonad
      at the time of sexual differentiation and testis cord formation.

PMID- 16087174
TI  - Consequences of noggin expression by neural stem, glial, and neuronal precursor
      cells engrafted into the injured spinal cord.
AB  - Bone morphogenetic proteins (BMPs) are a large class of secreted factors, which
      serve as modulators of development in multiple organ systems, including the CNS.
      Studies investigating the potential of stem cell transplantation for restoration
      of function and cellular replacement following traumatic spinal cord injury (SCI)
      have demonstrated that the injured adult spinal cord is not conducive to
      neurogenesis or oligodendrogenesis of engrafted CNS precursors. In light of
      recent findings that BMP expression is modulated by SCI, we hypothesized that
      they may play a role in lineage restriction of multipotent grafts. To test this
      hypothesis, neural stem or precursor cells were engineered to express noggin, an
      endogenous antagonist of BMP action, prior to transplantation or in vitro
      challenge with recombinant BMPs. Adult rats were subjected to both contusion and
      focal ischemic SCI. One week following injury, the animals were transplanted with
      either EGFP- or noggin-expressing neural stem or precursor cells. Results
      demonstrate that noggin expression does not antagonize terminal astroglial
      differentiation in the engrafted stem cells. Furthermore, neutralizing endogenous
      BMP in the injured spinal cord significantly increased both the lesion volume and
      the number of infiltrating macrophages in injured spinal cords receiving noggin
      expressing stem cell grafts compared with EGFP controls. These data strongly
      suggest that endogenous factors in the injured spinal microenvironment other than
      the BMPs restrict the differentiation of engrafted pluripotent neural stem cells
      as well as suggest other roles for BMPs in tissue protection in the injured CNS.

PMID- 16087175
TI  - Plasmodium chabaudi adami: use of the B-cell-deficient mouse to define possible
      mechanisms modulating parasitemia of chronic malaria.
AB  - Our previous observation that B-cell-deficient JH-/- mice utilize T cell
      dependent immunity to suppress acute Plasmodium chabaudi adami-induced malaria
      but then develop chronic low-level parasitemia prompted this study of control
      mechanisms for chronic parasitemia. When we infected JH-/- mice with blood-stage
      parasites, chronic parasitemia exacerbated after the 6th month and persisted for
      up to 17 months. This exacerbation of parasitemia could not be attributed to host
      aging because the time-course of acute infection in naive aged mice was nearly
      identical to that seen in young mice. Nor could exacerbated parasitemia be
      attributed to mutation in the parasite genome resulting in increased virulence;
      when subinoculated into naive JH-/- mice, parasites from chronically infected JH
      /- mice with exacerbated parasitemia produced acute stage parasitemia profiles in
      most recipients comparable to those seen in JH-/- mice upon infection with the
      original stabilate material. Of the pro-inflammatory cytokines measured,
      including IFNgamma, TNFalpha, IL-12p70, and MCP-1beta, none were significantly
      different in the sera of mice with exacerbated parasitemia compared to uninfected
      controls. Levels of IL-6 were significantly (P=0.002) less in the sera of mice
      with exacerbated parasitemia. Serum levels of the anti-inflammatory cytokine,
      TGFbeta, were significantly depressed in chronically infected JH-/- mice compared
      to uninfected controls. In contrast, IL-10 levels were markedly increased. These
      findings suggest that the cytokine balance may be disturbed during chronic
      malaria, thereby impacting on mechanisms that modulate levels of parasitemia.

PMID- 16087176
TI  - Setaria cervi: kinetic studies of filarial glutathione synthetase by high
      performance liquid chromatography.
AB  - The bovine filarial worm Setaria cervi was found to have abundance of glutathione
      synthetase (GS; EC 6.3.2.3) activity, the enzyme being involved in catalysing the
      final step of glutathione (GSH) biosynthesis. A RP-HPLC method involving
      precolumn derivatization with o-phthalaldehyde has been followed for the
      estimation of GS activity in crude filarial preparations. Subcellular
      fractionation of the enzyme was undertaken and it was confirmed to be a soluble
      protein residing mainly in cytosolic fraction. Attempts to determine the Km value
      for L-gamma-glutamyl-L-cysteine gave a distinctly nonlinear double-reciprocal
      plot in which data obtained at relatively high dipeptide concentrations (>1 mM)
      extrapolate to a Km value of about 400 microM whereas data obtained at lower
      concentrations (<0.1 mM) extrapolate to a value of about 33 microM. Km was
      determined to be around 950 and 410 microM for ATP and glycine, respectively. The
      effect of various amino acids was studied on enzyme activity at 1mM
      concentration. L-cystine caused a significant enzyme inhibition of 11%.
      Preincubation with N-ethylmaleimide also resulted in significant inhibition of GS
      activity.

PMID- 16087177
TI  - Defective binding of transcriptional repressor ZEB via DNA methylation
      contributes to increased constitutive levels of p73 in Fanconi anemia cells.
AB  - Little is known about the molecular mediators of the Fanconi anemia (FA) pathway
      involved in the machinery that maintains genomic integrity. Here, we report that
      the levels of p73 and its target genes, are increased in cells derived from FA
      patients belonging to complementation group A (FA-A). Moreover, functional
      correction of FA-A cells by gene transfer reduces the expression of p73. We also
      demonstrate that DNA methylation contributes to increased levels of p73 in FA-A
      cells by hampering the binding of the transcriptional repressor ZEB to an
      intronic regulatory region of the p73 gene. Together, our data may help explain
      the susceptibility of these cells to DNA damaging agents.

PMID- 16087178
TI  - A transposon-based activation-tagging population in Arabidopsis thaliana (TAMARA)
      and its application in the identification of dominant developmental and metabolic
      mutations.
AB  - A population of 9471 stable activation-tagged lines was generated by transposable
      element mediated activation tagging mutagenesis in Arabidopsis (TAMARA) using the
      maize En/Spm transposon system. Based on DNA gel blot and flanking sequence
      analysis, this population contains approximately 6000 independent transposon
      insertions. A greenhouse-based screen identified six dominant or semi-dominant
      activation tagged mutants with obvious developmental alterations, among these a
      new pistillata mutant allele. In addition, a subset of 1500 lines was screened by
      a HPLC based high-throughput method for dominant activation tagged mutants with
      enhanced contents of phenolic compounds. One dominant activation tagged mutant
      (hpc1-1D) was isolated showing accumulation of a particular compound due to the
      upregulation of an R2R3-MYB transcription factor.

PMID- 16087179
TI  - NosX function connects to nitrous oxide (N2O) reduction by affecting the Cu(Z)
      center of NosZ and its activity in vivo.
AB  - The effect of loss of the 34-kDa periplasmic NosX protein on the properties of
      N2O reductase was investigated with an N2O-respiration negative, double mutant of
      the paralogous genes nosX and nirX of Paracoccus denitrificans. In spite of
      absence of whole-cell N2O-reducing activity, the purified reductase was
      catalytically active, which attributes NosX a physiological role in sustaining
      the reaction cycle. N2O reductase exhibited the spectroscopic features of Cu(A)
      and the redox-inert, paramagnetic state, Cu(Z)*, of the catalytic center. Cu(Z)*,
      hitherto considered the result of spontaneous reaction of the reductase with
      dioxygen, attains cellular significance.

PMID- 16087180
TI  - Oxygenated complex of cytochrome bd from Escherichia coli: stability and
      photolability.
AB  - Cytochrome bd is one of the two terminal ubiquinol oxidases in the respiratory
      chain of Escherichia coli catalyzing reduction of O2 to H2O. The enzyme is
      expressed under low oxygen tension; due to high affinity for O2 it is isolated
      mainly as a stable oxygenated complex. Direct measurement of O2 binding to heme d
      in the one-electron reduced isolated enzyme gives K(d(O2)) of approximately 280
      nM. It is possible to photolyse the heme d oxy-complex by illumination of the
      enzyme for several minutes under microaerobic conditions; the light-induced
      difference absorption spectrum is virtually identical to the inverted spectrum of
      O2 binding to heme d.

PMID- 16087181
TI  - The role of PKCalpha and RLIP76 in transport-mediated doxorubicin-resistance in
      lung cancer.
AB  - In deletion mutant analyses of potential phosphorylation sites in RLIP76, we
      identified T297 and S509 as targets for phosphorylation by PKCalpha.
      Phosphorylation at T297 increased doxorubicin (DOX)-transport activity
      approximately 2-fold for RLIP76 purified from recombinant source, or from three
      small (H69, H1417, H1618) and three non-small cell, one each derived from H226
      (squamous), H358 (bronchio alveolar), and H1395 (adenocarcinoma) lung cancer cell
      lines. T297 phosphorylation conferred sensitivity to tryptic digestion at R293.
      The specific activity for DOX-transport by RLIP76 purified from non-small cell,
      which was primarily in the phosphorylated form, was approximately twice that in
      small cell lung cancer cell lines. These finding offer a novel explanation for
      the observed intrinsic differences in sensitivity to DOX between non-small cell
      and small cell lung cancer cell lines.

PMID- 16087182
TI  - Synechocystis ferredoxin/ferredoxin-NADP(+)-reductase/NADP+ complex: Structural
      model obtained by NMR-restrained docking.
AB  - Ferredoxin (Fd) and ferredoxin-NADP(+)-reductase (FNR) are two terminal
      physiological partners of the photosynthetic electron transport chain. Based on a
      nuclear magnetic resonance (NMR)-restrained-docking approach, two alternative
      structural models of the Fd-FNR complex in the presence of NADP+ are proposed.
      The protein docking simulations were performed with the software BiGGER. NMR
      titration revealed a 1:1 stoichiometry for the complex and allowed the mapping of
      the interacting residues at the surface of Fd. The NMR chemical shifts were
      encoded into distance constraints and used with theoretically calculated
      electronic coupling between the redox cofactors to propose experimentally
      validated docked complexes.

PMID- 16087183
TI  - Formulation and investigation of 5-FU nanoparticles with factorial design-based
      studies.
AB  - This study describes an orthogonal experimental design to optimize the
      formulation of 5-fluorouracil (5-FU) loaded poly D,L (lactide-co-glycolide)
      (PLGA) nanoparticles (5FU-NP) by a nanoprecipitation-solvent displacement
      technique. The type of surfactant, amount of acetone and molecular weight of the
      polymer with three levels of each factor were selected and arranged in an
      L18(3(5)) orthogonal experimental table. From the statistical analysis of the
      data polynominal equations were generated. Optimized formulations have the
      particle size ranging from 160 to 250 nm. Smallest nanoparticles (161+/-1.22 nm)
      were obtained using Resomer PLGA 755 and pluronic F-68 with 10 ml acetone amount.
      Under these conditions the 5-FU entrapment percentage was maximum 78.30%,
      suggesting 5-FU might be entrapped and adsorbed on the nanoparticle surface. In
      vitro release of three formulations with maximum drug entrapment efficiency and
      minimum particle size, were also investigated by release kinetics. According to
      the determined coefficients, release data fit to Higuchi's diffusion kinetics.
      The in vitro release of 5FU-NP in phosphate buffered saline (PBS, pH 7.4) is
      suggested to be controlled by a combination of diffusion with slow and gradual
      erosion of the particles. Also, the antimicrobial activity was observed even on
      the end of seventh day with all formulations.

PMID- 16087184
TI  - Resource defense and juvenile hormone: the "challenge hypothesis" extended to
      insects.
AB  - As predicted for vertebrates by the challenge hypothesis, the endocrine system of
      invertebrates can respond to social stimuli to modulate aggression. Testosterone
      (T) is generally considered to moderate aggression associated with reproduction,
      i.e. the establishment of breeding territories, mate guarding and offspring
      defense; juvenile hormone (JH) serves an analogous function in burying beetles.
      Hemolymph titers of JH increase significantly in Nicrophorus orbicollis, a
      species with facultative biparental care, when challenged by an intruder to
      defend their resource. During the first 12 h after the discovery of a carcass,
      the necessary breeding resource, competition is intrasexual, and JH of males
      responds only to a challenge by males, and JH of females responds only to a
      challenge by female intruders. After this period, competition is intersexual, and
      JH increases significantly in both males and females challenged by an intruder of
      either sex. In contrast, JH titers in a nonparental species are much higher
      throughout the breeding season, and neither males nor females respond hormonally
      to an intruder. These findings support the challenge hypothesis and suggest that
      mating systems and breeding strategies can promote plastic responses in insect,
      as well as vertebrate, endocrine systems.

PMID- 16087185
TI  - Modeling spreading-pressure-dependent binary gas coadsorption equilibria using
      gravimetric data.
AB  - The present work proposes an approach to building nonideal coadsorption models in
      a thermodynamically consistent fashion, including the effects of pressure and
      spreading pressure, from simple gravimetric measurements. This is an "inverse
      problem" of parameter determination from appropriate and limited experimental
      data. The approach relies on the nonideal adsorbed solution theory, which
      includes activity coefficients and their dependence on spreading pressure, and on
      an original form of the excess Gibbs energy of mixing. A fully analytical
      development leads to explicit relations between the infinite dilution activity
      coefficients and three sets of independent information: the parameters of this
      excess Gibbs function, the limiting slopes of measured binary gravimetric curves
      at two different total pressures, and the properties of the single-component
      isotherms. From there, the four parameters of the model may be determined quasi
      analytically and uniquely. The method is exemplified with the coadsorption of
      CO(2) and CH(4) on activated carbon, and a heterogeneous set of data. On one
      hand, the total adsorbed mass of the two components is measured at 1 bar by
      "incremental gravimetry." On the other hand, data obtained from independent batch
      type equilibration measurements at 2 bar allow a comparison of calculated and
      measured data for the individual component concentrations. It is emphasized,
      however, that only total adsorbed mass data are needed for application of the
      method.

PMID- 16087186
TI  - Sphere to rod transitions in homologous alkylpyridinium salts: a Stauff-Klevens
      type equation for the second critical micelle concentration.
AB  - In the present paper, we analyze the dependence of the second critical micelle
      concentration (second cmc) of ionic amphiphiles on the number of atoms in the
      hydrocarbon molecular chain, n(c). A molecular thermodynamic model for the
      interaction energy between the end caps of rodlike micelles, g(N), is introduced
      and the linear dependence of this object on n(c) analyzed, thus leading to a
      Stauff-Klevens-like behavior of the second cmc. The predictions agree with
      previously reported data for n-alkyldimethylbenzylammonium chloride (C(n)BACl)
      for n-alkylpyridinium chloride (C(n)PyCl) and n-alkyltrymethylammonium bromide
      (C(n)TABr) at 35 degrees C. These conclusions are reinforced by the conductivity,
      density, and ultrasound velocity measurements of the second cmc of several
      C(n)PyCl (n=12, 14, 16) and n-alkylpyridinium bromides (C(n)PyBr, n=12, 14, 15,
      16) presented in this paper.

PMID- 16087187
TI  - The effects of spelling consistency on phonological awareness: a comparison of
      English and German.
AB  - Within alphabetic languages, spelling-to-sound consistency can differ
      dramatically. For example, English and German are very similar in their
      phonological and orthographic structure but not in their consistency. In English
      the letter a is pronounced differently in the words bank, ball, and park, whereas
      in German the letter a always has the same pronunciation (e.g., Ball, Park,
      Bank). It is often argued that reading acquisition has a reciprocal effect on
      phonological awareness. As reading is acquired, therefore, spoken language
      representation may be affected differently for English and German children. Prior
      to literacy acquisition, however, phonological representation in English and
      German children should be similar due to the similar phonological structure of
      the two languages. We explored this hypothesis by comparing phonological
      awareness at the rime and phoneme levels in prereaders and beginning readers in
      English and German. Similar developmental effects were indeed observed in
      prereaders, but differential effects had emerged within the first year of reading
      instruction.

PMID- 16087188
TI  - Genetic contributors toward increased risk for ischemic heart disease.
AB  - Cardiovascular disease is a leading cause of mortality in the United States, and
      is a significant cause of death worldwide. In 2002, it accounted for 38.0% of all
      deaths in the US, and approximately one-third of all global deaths. It has a
      significant economic impact, with an estimated cost in the US of 393.5 billion US
      dollars for 2005. The most common form of heart disease is coronary heart disease
      (CHD)(1)/coronary artery disease (CAD) resulting from atherosclerosis. Thirteen
      million Americans are affected by CHD annually, with 7.1 million of these
      experiencing a myocardial infarction (MI). Five to ten percent of new MI's occur
      in individuals younger than age 50, and the lifetime risk of developing CAD after
      age 40 ranges from 32% in women to 49% in men. Because of its major impact on
      morbidity and mortality, as well as its contribution to annual health care costs,
      it is of the utmost importance that improved strategies for preventing and
      treating CAD be developed. A promising, but inherently difficult, area of study
      is the identification of genes that predispose to or directly cause CAD. The
      identification of these genes may lead to screening tests that will allow persons
      at risk for developing CAD to be identified early enough that
      prevention/intervention strategies can be implemented to prevent or ameliorate
      the disease process, and may also lead to the development of gene therapy
      mechanisms useful in the treatment of ischemic heart disease (IHD). Because an
      exhaustive review of all the genes being studied in relation to CAD and MI is
      difficult within the confines of a review article, this review will focus on
      describing representative studies investigating the genes considered most likely
      to potentially contribute toward an increased risk for CAD and MI. Genes
      resulting in inherited disorders with which an increased risk of CAD and MI is
      associated will be discussed, as well as a number of candidate genes that may
      play a role in the multifactorial inheritance of CHD risk.

PMID- 16087189
TI  - A calcium channel blocker amlodipine increases coronary blood flow via both
      adenosine- and NO-dependent mechanisms in ischemic hearts.
AB  - Amlodipine reduces oxidative stress that decreases NO and adenosine release. This
      study was undertaken to examine whether amlodipine mediates coronary vasodilation
      and improves myocardial metabolism and contractility in ischemic hearts via
      either adenosine- or NO-dependent mechanisms. In open-chest dogs, amlodipine (2
      mug kg per min) was infused at the minimum dose that caused maximal coronary
      vasodilation. The perfusion pressure was reduced in the left anterior descending
      coronary artery so that coronary blood flow (CBF) decreased by 50%. Amlodipine
      increased the difference of the adenosine level (VAD (Ado): 119+/-14 to 281+/-46
      nM) and the nitrate+nitrite level (VAD (NOx): 7.8+/-1.3 to 16.1+/-1.1 muM)
      between coronary venous and coronary arterial blood, and also increased CBF (50+/
      3 to 69+/-6 ml/100 g/min). These changes were partially reversed by either 8
      sulfophenyeltheophylline (8SPT) or l(omega)-nitro arginine methyl ester (l-NAME),
      and were completely blocked by both 8SPT and l-NAME. The reduction of CBF
      increased VAD (8-iso-prostaglandin F(2alpha)), and this increase was reduced by
      amlodipine (10.8+/-1.1 to 5.0+/-0.5 pg/ml). In addition, pretreatment with
      superoxide dismutase mimicked the coronary effects of amlodipine and blunted the
      response to amlodipine administration. Amlodipine-induced coronary vasodilation
      via both adenosine- and NO-dependent mechanisms. Adenosine and NO may interact in
      ischemic hearts to mediate coronary vasodilation by amlodipine.

PMID- 16087190
TI  - Lysozyme binding to endocardial endothelium mediates myocardial depression by the
      nitric oxide guanosine 3',5' monophosphate pathway in sepsis.
AB  - Inflammatory mediators have been implicated as a cause of reversible myocardial
      depression in septic shock. We previously reported that the release of lysozyme-c
      (Lmz-S) from leukocytes from the spleen or other organs contributes to myocardial
      dysfunction in Escherichia coli septic shock in dogs by binding to a cardiac
      membrane glycoprotein. However, the mechanism by which Lzm-S causes this
      depression has not been elucidated. In the present study, we tested the
      hypothesis that the binding of Lzm-S to a membrane glycoprotein causes myocardial
      depression by the formation of nitric oxide (NO). NO generation then activates
      soluble guanylyl cyclase and increases cyclic guanosine monophosphate (cGMP),
      which in turn triggers contractile impairment via activation of cGMP-dependent
      protein kinase (PKG). We examined these possibilities in a right ventricular
      trabecular preparation in which isometric contraction was used to measure cardiac
      contractility. We found that Lzm-S's depressant effect could be prevented by the
      non-specific NO synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA). A
      guanylyl cyclase inhibitor (ODQ) and a PKG inhibitor (Rp-8-Br-cGMP) also
      attenuated Lzm-S's depressant effect as did chemical denudation of the
      endocardial endothelium (EE) with Triton X-100 (0.5%). In EE tissue, we further
      showed that Lzm-S caused NO release with use of 4,5 diaminofluorescein, a
      fluorescent dye that binds to NO. The present study shows that the binding of Lzm
      S to EE generates NO, and that NO then activates the myocardial guanosine 3',5'
      monophosphate pathway leading to cardiac depression in sepsis.

PMID- 16087191
TI  - Differential role of vagus nerve in maintaining diurnal gene expression rhythms
      in the proximal small intestine.
AB  - BACKGROUND: We have documented previously diurnal rhythms in intestinal sugar
      transporter expression. We set out to identify the role of the vagus nerve in
      these rhythms. MATERIALS AND METHODS: Sprague-Dawley rats underwent truncal
      vagotomy (V; n = 9) and were pair-fed with sham-operated (n = 4) and unoperated
      rats (n = 6). Rats were killed at ZT3 and ZT9 (ZT: Zeitgeber time with ZT0 set at
      lights-on), the time interval over which sucrase, SGLT1, GLUT2, and GLUT5
      expression exhibit significant anticipatory increases. Jejunal RNA expression for
      the four genes were assessed by Northern blot analysis. SGLT1 and GLUT2
      expression was further studied by Western blot analysis and in situ
      hybridization. RESULTS: Control rats (sham-operated plus unoperated rats)
      exhibited the expected increase in RNA levels at ZT9 versus ZT3 for SGLT1, GLUT2,
      GLUT5, and sucrase (P < 0.01 for each). The diurnal rhythm of mRNA levels for
      GLUT2 and sucrase, but not for SGLT1 or GLUT5, were blunted in V rats. At protein
      level, SGLT1 was induced 4.3-fold in control rats (P < 0.01) and 3.8-fold in V
      rats (P < 0.01), whereas GLUT2 was induced 3.3-fold in control rats (P < 0.01)
      but only 1.4-fold in V rats (N.S.). CONCLUSIONS: Our results indicate that
      signaling through the vagus nerve is necessary for the anticipatory induction of
      GLUT2 and sucrase. Persistence of normal rhythms in both SGLT1 and GLUT5
      indicates that diurnal induction of these genes is independent of vagal
      innervation. Entrainment of anticipatory diurnal gene expression in the intestine
      occurs via two separate pathways that are differentially dependent on vagal
      input.

PMID- 16087193
TI  - Beneficial effects of intravenous administration of lipo-prostaglandin E1 on the
      ischemic gastric tube in pigs.
AB  - INTRODUCTION: Lipo-prostaglandin E1 (PGE1) is a new preparation of PGE1 in which
      it is bound to lipids to slow PGE1 release and delay its rate of metabolism. We
      investigated the change of the blood flow on impaired microcirculation of the
      ischemic gastric tube in pigs after saline, unmodified PGE1, and lipo-PGE1
      administration. MATERIALS AND METHODS: The gastric tube was constructed using 15
      domestic pigs under general anesthesia, and saline, unmodified PGE1, and lipo
      PGE1 were infused continuously at a rate of 0.05 microg/kg/min for 10 min. Tissue
      blood flow (TBF) and the serum PGE1 concentration were analyzed before
      administration, after administration for 10 min, and 10 min after the end of
      administration. RESULTS: There were no obvious changes in TBF during the
      administration of saline. However, TBF during treatment with unmodified PGE1 and
      lipo-PGE1 was significantly increased to 13.0 +/- 1.3 and 13.9 +/- 1.3 ml/min/100
      g, respectively (paired t-test; P < 0.01). Although TBF was significantly
      decreased to 8.0 +/- 1.0 ml/min/100 g on 10 min after the end of unmodified PGE1
      administration (paired t-test; P < 0.01), it was maintained over 10 ml/min/100 g
      in lipo-PGE1 group. The serum PGE1 concentration during treatment with unmodified
      PGE1 and lipo-PGE1 was significantly increased to 229 +/- 21 and 225 +/- 9 pg/ml
      (paired t-test; P < 0.01), however, it was significantly decreased to 59 +/- 5
      and 131 +/- 17 pg/ml (paired t-test; P < 0.01), respectively, on 10 min after the
      end of administration. However, the serum PGE1 concentration in lipo-PGE1 group
      was significantly higher than that in unmodified PGE1 group (unpaired t-test; P <
      0.01). CONCLUSION: Lipo-PGE1 infusion leads to the objectively measurable
      improvement and the prolonged action in the blood perfusion of the gastric tube
      in pigs. Therefore, treatment with lipo-PGE1 infusion can increase TBF at the
      anastomotic site, and it may be beneficial for preventing anastomotic leakage in
      boluses for a couple of times a day.

PMID- 16087192
TI  - IL-10 plasma levels are elevated after LPS injection in splenectomized A/J mice.
AB  - BACKGROUND: Splenectomy is clinically indicated in certain cases of hypersplenism
      and splenic trauma. However, it is associated with serious complications, in
      particular, reduced clearance of encapsulated organisms and a high incidence of
      sepsis, which has been coined overwhelming post-splenectomy sepsis (OPSS). In
      addition to the role of the spleen in the clearance of microorganisms, this organ
      may be involved in regulation of the inflammatory response. We investigated the
      effect of splenectomy on the inflammatory process induced by LPS in a murine
      model that resembles, in part, the pathophysiological aspects of sepsis.
      MATERIALS AND METHODS: Male mice (8-weeks-old) from different inbred strains were
      randomized into three groups: splenectomized (SPX), sham operated (SHAM), and non
      operated controls (NoOp). After 9 days of recovery, mice were injected with LPS
      (15 mg/kg) and cytokine plasma levels were measured by ELISA at 1.5 or 6 h after
      injection. Peritoneal macrophages (PMphi) were isolated from the three groups,
      and cytokine production was evaluated after incubation with LPS in culture
      conditions. RESULTS: IL-10 plasma levels were elevated in SPX A/J mice (6.7 +/-
      0.4 mug/ml) after injection of LPS (15 mg/kg) compared to NoOp A/J mice (4.2 +/-
      0.2 mug/ml, P < 0.05). Similar elevation in IL-10 plasma levels was detected in
      SPX DBA/2J mice as compared to NoOp DBA/2J mice, but not in C57BL/6J and BALB/cJ
      mice. In contrast, SPX AKR mice displayed lower IL-10 levels than NoOp mice.
      PMphis from SPX A/J mice produced elevated levels of IL-10 compared to PMphis
      from SHAM or NoOp A/J mice, mimicking the in vivo observations. CONCLUSION: Our
      data suggest that the spleen plays an important role in modulating the
      inflammatory process induced by LPS, extending beyond passive clearance of
      encapsulated organisms. In addition, the contribution of the spleen to the
      inflammatory process may be influenced by the genetic background.

PMID- 16087194
TI  - The effect of six different statins on the proliferation, migration, and invasion
      of human smooth muscle cells.
AB  - Intimal hyperplasia (IH) can occur after any vascular injury and results from
      smooth muscle cells (SMC) proliferation, migration, and invasion into the
      subintimal space. The purpose of this study was to investigate the effect of six
      different statins on the proliferation, migration, and invasion of human venous
      SMC. The statins were all used at their Cmax concentrations. SMCs were used to
      construct growth curves in the presence of 10% fetal calf serum or 10% fetal calf
      serum supplemented with the six statins. Migration and invasion experiments were
      performed using modified Boyden chambers. The invasion experiments were performed
      using Matrigel coated plates. We found that all of the statins significantly
      inhibited SMC proliferation compared to the platelet-derived growth factor
      control (ranging from fluvastatin 33% of control to pravastatin 72% of control, P
      = 0.03). SMC migration through uncoated polycarbonate membranes in presence of
      the six statins was significantly reduced (ranging from lovastatin 43% to
      pravastatin 57% of control, P = 0.006). All six statins also significantly
      reduced SMC invasion (ranging from fluvastatin 65% to simvastatin 87% of control,
      P = 0.002). We conclude that the inhibitory effect of statins on SMC
      proliferation, migration, and invasion is a class, rather than drug specific
      effect.

PMID- 16087195
TI  - Beneficial effects of oral insulin on intestinal recovery following ischemia
      reperfusion injury in rat.
AB  - BACKGROUND: It has been reported that oral insulin has a trophic effect on
      intestinal mucosa, but the precise mechanism of its action is still unclear. The
      purpose of the present study was to investigate the effect of oral insulin on
      ischemia-reperfusion (IR) intestinal mucosal injury in rat. MATERIALS AND
      METHODS: Male Sprague-Dawley rats underwent laparotomy (Sham) or IR-intestinal
      damage by clamping both the superior mesenteric artery and the portal vein for 30
      min followed by 24 h reperfusion. IR-INS rats were treated with oral insulin
      given in drinking water (1U/ml) 48 h before and after IR. Intestinal structural
      changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h
      after IR. Park's score was used for the quantitative assessment of histological
      change. A non-parametric Kruskal-Wallis ANOVA test was used for statistical
      analysis with P less than 0.05 considered statistically significant. RESULTS: IR
      injury resulted in a significant decrease in bowel weight in jejunum, mucosal
      weight in jejunum and ileum, villus height in jejunum and ileum, cell
      proliferation index in jejunum, and ileum compared to sham animals. IR-INS
      animals demonstrated greater duodenal and jejunal bowel weight, duodenal, jejunal
      and ileal mucosal weight, jejunal mucosal DNA, jejunal and ileal mucosal protein,
      jejunal and ileal villus height and crypt depth, jejunal and ileal proliferation
      index compared to IR-animals. Oral insulin administration induced also a
      significant decrease in apoptotic index in ileum (1.2 +/- 0.4 versus 2.8 +/- 0.7
      TUNEL positive cells/10 villi, P < 0.05) compared to IR-untreated animals.
      CONCLUSIONS: Oral insulin improves intestinal recovery after IR- injury in rat.

PMID- 16087197
TI  - Continuing observation of disturbed reproductive cycle and ovarian
      spermatogenesis in the giant abalone, Haliotis madaka from an organotin
      contaminated site of Japan.
AB  - Histological examination of gonads as well as chemical analysis of organotin
      compounds in tissues of the giant abalone, Haliotis madaka, was conducted to
      evaluate continuing endocrine disruption in abalone populations in Japan. Abalone
      specimens were collected from two different areas, Tsushima as a reference site
      and Jogashima as a site representative of declining abalone populations where
      serious organotin contamination had been observed, each month from January 1998
      to March 1999. Scores were given to the development stages of reproductive cells
      in the ovary and testis. The degree of sexual maturation was evaluated by
      calculating the mean value of a histogram of these scores for the reproductive
      cells of each abalone. The temporal variations in degree of sexual maturation
      showed that female and male abalone from Tsushima matured synchronously, while
      those from Jogashima did not, which were similar to results of the previous study
      during September 1995-November 1996. Approximately 19% of the female abalone from
      Jogashima were masculinized with an ovo-testis, which was also similar to the
      result of the previous study. The masculinization of female abalone is reported
      to be induced by tributyltin (TBT) and triphenyltin (TPhT) from antifouling
      paints. Concentrations of the sum of butyltins (TBT, dibutyltin (DBT) and
      monobutyltin (MBT): SigmaBTs) and the sum of phenyltins (TPhT, diphenyltin (DPhT)
      and monophenyltin (MPhT): SigmaPhTs) in the muscle of abalone from Jogashima (n =
      73) of 7.8+/-9.0 ng/g wet wt. and 4.5+/-6.8 ng/g wet wt., respectively, were
      significantly higher than those from Tsushima (n = 87) of 4.7+/-4.9 ng/g wet wt.
      and 0.8+/-1.7 ng/g wet wt., respectively (p < 0.05 for SigmaBTs; p < 0.001 for
      SigmaPhTs), although concentrations of TBT and TPhT in the muscle of abalone from
      Jogashima (n = 73) of 2.2+/-2.5 ng/g wet wt. and 5.8+/-5.1 ng/g wet wt.,
      respectively, were insignificantly and significantly higher than those from
      Tsushima (n = 87) of 0.4+/-0.6 ng/g wet wt. and 0.5+/-0.9 ng/g wet wt.,
      respectively, (p > 0.05 for TBT; p < 0.001 for TPhT). Thus, endocrine disruption
      as well as contamination by organotins in the giant abalone from Jogashima is
      still persisting.

PMID- 16087196
TI  - The cellular mRNA expression of GABA and glutamate receptors in spinal motor
      neurons of SOD1 mice.
AB  - ALS is a fatal neurodegenerative disorder characterized by a selective loss of
      upper motor neurons in the motor cortex and lower motor neurons in the brain stem
      and spinal cord. About 10% of ALS cases are familial, in 10-20% of these,
      mutations in the gene coding for superoxide dismutase 1 (SOD1) can be detected.
      Overexpression of mutated SOD1 in mice created animal models which clinically
      resemble ALS. Abnormalities in glutamatergic and GABAergic neurotransmission
      presumably contribute to the selective motor neuron damage in ALS. By in situ
      hybridization histochemistry (ISH), we investigated the spinal mRNA expression of
      the GABAA and AMPA type glutamate receptor subunits at different disease stages
      on spinal cord sections of mutant SOD1 mice and control animals overexpressing
      wild-type SOD1 aged 40, 80, 120 days and at disease end-stage, i.e. around 140
      days) (n=5, respectively). We detected a slight but statistically significant
      decrease of the AMPA receptor subunits GluR3 and GluR4 only in end stage disease
      animals.

PMID- 16087198
TI  - Gestational mutations and carcinogenesis.
AB  - We present a mathematical formulation to evaluate the effects of gestational
      mutations on cancer risk. The hazard or incidence function of cancer is expressed
      in terms of the Probability Generating Function (PGF) of the number of normal and
      mutated cells at birth. Using Filtered Poisson Process Theory, we obtain the PGF
      for several models for the accumulation of gestational mutations. In particular,
      we develop expressions for the hazard function when one or two successive
      mutations could occur during gestation. We also calculate the hazard when the
      background gestational mutation rates are increased due to exposure to mutagens,
      such as prenatal radiation. To illustrate the use of our models, we apply them to
      colorectal cancer in the SEER database. We find that the proportion of cancer
      risk attributable to developmental mutations depends on age and that it could be
      quite significant when gestational mutation rates are high. The analysis of the
      SEER data also shows that gestational mutations could contribute to inter
      individual variations in colorectal cancer risk.

PMID- 16087199
TI  - Differential E-selectin expression by iris versus retina microvascular
      endothelial cells cultured from the same individuals.
AB  - The microvasculature of the eye plays a critical role in many ophthalmic
      diseases, including diabetic retinopathy and macular degeneration.
      Transcriptional profiling by gene array allows characterization of endothelial
      cells (EC) and can test for inherent EC diversity relative to the tissue source
      of the EC. Here, we established highly purified microvascular EC cultures from
      donor-matched human irises and retinae (4 donor pairs). We used nylon-based gene
      array kits to compare gene expression in paired confluent EC monolayers, under
      both quiescent and inflammatory agent (bacterial lipopolysaccharide, LPS; or
      tumor necrosis-factor alpha, TNFalpha)-activated conditions. In the absence of an
      inflammatory agent, iris and retinal ECs from the same donor were remarkably
      similar in overall gene expression profiles, except for possible differences in
      the expression of platelet-derived growth factor-A and a DNA mismatch repair
      protein (mutL homologue). Several detectable transcripts had never previously
      been reported in the eye. After inflammatory stimulation, significantly greater
      expression of the adhesion molecule E-selectin mRNA was consistently detected in
      retinal versus iris EC, and this difference was maintained at the protein level
      both in cell-surface-expressed and secreted soluble E-selectin protein in paired
      cultures. Thus, cultured EC derived from adjacent microvascular beds are
      biologically distinct. Such endothelial diversity could play a role in the
      pathogenesis of tissue-specific inflammation, infection, neovascularization, and
      malignancy.

PMID- 16087200
TI  - Multiple drug resistance, antimutagenesis and anticarcinogenesis.
AB  - Many cells are protected from excess levels of exogenous chemicals, including
      mutagens and carcinogens as well as pharmaceutical agents, by being actively
      extruded through the action of one or more of a series of ATP-binding cassette
      drug transporter proteins. Those known to be important in humans are the
      multidrug resistance proteins (P-glycoproteins, encoded by the mdr1 and 3 genes),
      multidrug-resistance-associated proteins (MRP1-7) and the breast cancer
      resistance protein (BCRP). These proteins have overlapping but distinct cellular
      locations and substrate specificities, and jointly govern the likelihood of
      penetration or distribution of a given mutagen or carcinogen into various tissues
      including the brain, testis, ovaries and fetus. Thus, they can affect the
      absorption, distribution and excretion of mutagens and carcinogens, as well as of
      their metabolites and conjugates, in most cases acting to prevent or reduce
      mutagenesis or carcinogenesis. However, because ABC transporters may limit the
      success of chemotherapy, there has been a considerable effort by the
      pharmaceutical industry to develop inhibitors of this transport process, and
      these are increasing in use. In general, the mutagenicity of many chemicals may
      be increased at the cellular levels by the action of these inhibitors, while the
      altered absorption characteristics favour greater uptake into the body. Thus, in
      many cases, such inhibitors may counter the antimutagenic and anticarcinogenic
      effect of the multidrug resistance mechanisms. There are exceptions, however. An
      increasing number of single nucleotide polymorphisms in multidrug resistance
      genes are being identified in humans, and may account for many of the significant
      differences in inter-individual susceptibility to exogenous and endogenous
      mutagenic and carcinogenic insults.

PMID- 16087201
TI  - Pro-VGF-derived peptides induce penile erection in male rats: Involvement of
      paraventricular nitric oxide.
AB  - The effect of four peptides derived from the C-terminal portion of rat pro
      VGF(556-617) (VGF(556-576), VGF(588-617), VGF(599-617), and VGF(588-597)), on
      penile erection and nitric oxide production in the paraventricular nucleus of the
      hypothalamus was studied in male rats after injecting into this hypothalamic
      nucleus. VGF(588-617) (0.5, 1 and 2 microg), VGF(599-617) (0.5, 2 and 5 microg)
      and, to a lower extent, VGF(588-597) (2 and 5 microg) induced penile erection
      episodes when injected into the paraventricular nucleus and concomitantly
      increased paraventricular nitric oxide production, while VGF(556-576) (5 microg)
      was ineffective. VGF(588-617)-induced nitric oxide production was reduced by N(G)
      nitro-l-arginine methylester (l-NAME) (20 microg), a nitric oxide synthase
      inhibitor, which also reduced penile erection when injected in the
      paraventricular nucleus 15 min before the VGF peptide. The oxytocin receptor
      antagonist d(CH(2))(5)Tyr(Me)-Orn(8)-vasotocin (1 microg) also effectively
      reduced VGF(588-617)-induced penile erection when given into the lateral
      ventricles, but not when injected into the paraventricular nucleus. In both
      experimental conditions, d(CH(2))(5)Tyr(Me)-Orn(8)-vasotocin was unable to
      influence nitric oxide production in the paraventricular nucleus. The present
      results confirm that C-terminal pro-VGF-derived peptides induce penile erection
      when injected into the paraventricular nucleus and show that this effect is
      mediated by an increased nitric oxide production in this hypothalamic nucleus.
      Apparently, this causes the activation of paraventricular oxytocinergic neurons
      projecting to extra-hypothalamic brain areas and mediating penile erection, as
      found with dopamine agonists, oxytocin, excitatory amino acids and hexarelin
      analogue peptides.

PMID- 16087202
TI  - Primary neurologic screening and motor coordination of Dstdt-J mutant mice
      (dystonia musculorum) with spinocerebellar atrophy.
AB  - The autosomal recessive dystonia musculorum (Dst(dt-J)) mutation causes
      degenerative lesions of peripheral and central sensory pathways. A test battery
      of motor, sensory, postural, and autonomic functions was used to compare young
      control and homozygous Dst(dt-J) mice. The Dst(dt-J) mutants were severely
      impaired for muscle strength, limb coordination, and postural reflexes. As a
      result of a loss in motor control, the mutants were hypoactive in the open-field
      and fell quickly from the stationary beam. In sensory tests, the acoustic startle
      response was impaired, but not tactile reflexes and contact righting, attesting
      to preserved labyrinthine function and non-lemniscal pathways. Dst(dt-J) mutants
      were also distinguishable from controls on the basis of tremor, a paler skin,
      piloerection, and half-open eyes, as well as low body weight and fecal boli.
      Grooming episodes were less frequent in the mutants but without any reduction in
      grooming time. The neurologic screening battery delineated the functional
      integrity of some sensorimotor pathways in a spinocerebellar mutant whose severe
      phenotype prevents a more elaborate evaluation.

PMID- 16087203
TI  - Effects of hormonal replacement with androgens and estrogens on male sexual
      behavior and plasma levels of these steroids in gonadectomized golden hamsters
      (Mesocricetus auratus).
AB  - Because the endocrine control of sexual behavior in male hamsters remains
      controversial, this study analyzed the influence of different androgens and
      estrogens in the regulation of masculine, sexual behavior (MBS). Aromatizable
      androgens: androstenedione (A) and testosterone (T), a non-aromatizable androgen:
      5alpha-dihydrotestosterone (DHT), as well as estrogens (E2 and E1) alone or in
      combination with DHT, were administered in gonadectomized, sexually experienced
      males, for 3 weeks. In addition, plasma levels of these steroids were determined.
      Gonadectomy completely suppressed masculine sexual behavior (MSB) after 4 weeks.
      Both A and T replacements restored all the sexual behavior parameters in
      castrated hamsters by the 3rd week of treatment, with A being more potent in
      restoring all copulatory series and maintaining all MSB parameters, including
      long intromissions. Castrated males treated with DHT showed little interest in
      the female and did not display any copulatory behavior. Gonadectomized males
      treated with estrogens alone showed active anogenital investigation and displayed
      some mounts, but did not ejaculate. Males treated with estrogens combined with
      DHT had longer latencies and less number of ejaculations than males treated with
      aromatizable androgens. Long intromissions were observed only in males treated
      with T or A. Plasma levels of A were significantly higher than T levels in intact
      males. In males treated with A both androgens and estrogens were present in
      plasma. These results support the notion that aromatizable androgens, mainly A,
      but not non-aromatizable androgens or even estrogens in combination with DHT,
      play a relevant role in the endocrine regulation of MSB in the golden hamster.

PMID- 16087204
TI  - Public-private partnership: from there to here.
AB  - Major changes in research and development (R&D) for drugs to treat tropical and
      neglected diseases have occurred in the past five years. Public-private
      partnerships for product development (PD PPPs) have emerged since rising drug
      development costs pushed pharmaceutical companies out of R&D for these diseases
      of the developing world and are now having an impact on the discovery and
      development of new medicines to treat them. PD PPPs can be an efficient model for
      bridging the translational research gap between basic research and clinical
      development by bringing together expertise from academia, the pharmaceutical
      industry and the public sector. Sustainability of funding is a serious problem.
      At present, one or two key philanthropic organisations provide a large proportion
      of the funding. Drug development typically takes 10 years and only 10 per cent of
      initial projects make it into the clinic. The partnerships need to widen their
      funding base and ensure that the funders understand the high level of attrition.
      Public-private partnerships have proved that they can move compounds quickly
      through the R&D pipeline. The challenge is to ensure that the products are
      delivered to the people who need them and to ensure that scientists in endemic
      countries are involved in the whole process.

PMID- 16087205
TI  - Facing the challenge: the symposium in context.

PMID- 16087206
TI  - Inhibition of lipopolysaccharide-stimulated NO production by crotafuran B in RAW
      264.7 macrophages involves the blockade of NF-kappaB activation through the
      increase in IkappaBalpha synthesis.
AB  - Crotafuran B, a natural pterocarpanoid isolated from Crotalaria pallida,
      inhibited the lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production
      (IC50 16.4+/-0.7 microM) and inducible nitric oxide synthase (iNOS) protein and
      mRNA expression (IC50 11.5+/-0.6 microM and 11.8+/-2.2 microM, respectively), but
      not via its cytotoxicity or the inhibition of iNOS enzyme activity, in RAW 264.7
      macrophages. Crotafuran B also reduced the iNOS promoter activity (IC50 13.4+/
      0.1 microM) in piNOS-LUC-transfected cells. Crotafuran B treatment inhibited the
      p65 nuclear translocation and the nuclear factor-kappaB (NF-kappaB) DNA binding
      activity in LPS-activated macrophages. Crotafuran B also reduced the NF-kappaB
      transcriptional activity in pNF-kappaB-LUC-transfected cells. Crotafuran B had no
      effect on the LPS-induced phosphorylation of inhibitory kappaBalpha
      (IkappaBalpha), but enhanced the cellular level of IkappaBalpha that rebounded to
      the basal levels and increased the IkappaBalpha mRNA expression. These results
      indicate that the crotafuran B inhibition of NO production involves a decrease in
      the iNOS gene expression via the inhibition of NF-kappaB activation through the
      increase in IkappaBalpha synthesis.

PMID- 16087207
TI  - Optimization of sparse synthetic transmit aperture imaging with coded excitation
      and frequency division.
AB  - An effective aperture approach is used for optimization of a sparse synthetic
      transmit aperture (STA) imaging system with coded excitation and frequency
      division. A new two-stage algorithm is proposed for optimization of both the
      positions of the transmit elements and the weights of the receive elements. In
      order to increase the signal-to-noise ratio in a synthetic aperture system,
      temporal encoding of the excitation signals is employed. When comparing the
      excitation by linear frequency modulation (LFM) signals and phase shift key
      modulation (PSKM) signals, the analysis shows that chirps are better for
      excitation, since at the output of a compression filter the sidelobes generated
      are much smaller than those produced by the binary PSKM signals. Here, an
      implementation of a fast STA imaging is studied by spatial encoding with
      frequency division of the LFM signals. The proposed system employs a 64-element
      array with only four active elements used during transmit. The two-dimensional
      point spread function (PSF) produced by such a sparse STA system is compared to
      the PSF produced by an equivalent phased array system, using the Field II
      simulation program. The analysis demonstrates the superiority of the new sparse
      STA imaging system while using coded excitation and frequency division. Compared
      to a conventional phased array imaging system, this system acquires images of
      equivalent quality 60 times faster, when the transmit elements are fired in pairs
      consecutively and the power level used during transmit is very low. The fastest
      acquisition time is achieved when all transmit elements are fired simultaneously,
      which improves detectability, but at the cost of a slight degradation of the
      axial resolution. In real-time implementation, however, it must be borne in mind
      that the frame rate of a STA imaging system depends not only on the acquisition
      time of the data but also on the processing time needed for image reconstruction.
      Comparing to phased array imaging, a significant increase in the frame rate of a
      STA imaging system is possible if and only if an equivalent time efficient
      algorithm is used for image reconstruction.

PMID- 16087208
TI  - Productive infection of Autographa californica nucleopolyhedrovirus in silkworm
      Bombyx mori strain Haoyue due to the absence of a host antiviral factor.
AB  - We have reported that several silkworm strains are permissive to
      intrahemocoelical infection of Autographa californica nucleopolyhedrovirus
      (AcNPV), contrary to the general belief that AcNPV cannot infect silkworm. In the
      present study, we address whether the intrahemocoelical infection of AcNPV to the
      silkworm was an exceptional phenomenon, and the possible genetic basis underlying
      it. Wilder range test of 31 strains of silkworm Bombyx mori for intrahemocoelical
      AcNPV infection led to the identification of 14 permissive strains and 17
      nonpermissive strains, indicating that the intrahemocoelical infection of AcNPV
      to the silkworm was not a rare and isolated phenomenon. Productive infection was
      shown in permissive silkworms, by EGFP fluorescence in various tissues when
      expression of reporter gene controlled by a very late viral promoter polh. The
      viral titer in larval hemolymph of permissive silkworms increased and maintained
      at a higher level hundredfold more than the initial amount of virus, indicating
      viral replication. A series of genetic cross experiments suggested the existence
      of only one dominant host anti-AcNPV gene or a set of genetically linked genes,
      which prevent AcNPV infection in nonpermissive silkworm strain Qingsong and are
      absent in permissive silkworm strain Haoyue.

PMID- 16087209
TI  - The cone inputs to the unique-hue mechanisms.
AB  - Our aim was to characterise the chromatic mechanisms that yield the four unique
      hues: red, green, yellow and blue. We measured the null planes for all four
      unique hues and report the following two main results. (1) We confirm that three
      chromatic mechanisms are required to account for the four unique hues. These
      three chromatic mechanisms do not coincide with the chromatic tuning found in
      parvocellular LGN neurones, i.e., neurones tuned to L-M and S-(L+M); these
      subcortical chromatic mechanisms are hence not the neural substrate of the
      perceptual unique hues and further higher-order colour mechanisms need to be
      postulated. Our results are consistent with the idea that the two higher-order
      colour mechanisms that yield unique red and unique green respectively combine the
      incremental and decremental responses of the subcortical chromatic mechanisms
      with different weights. In contrast, unique yellow and unique blue can be
      explained by postulating a single higher-order chromatic mechanism that combines
      the incremental and decremental subcortical chromatic responses with similar
      weights. (2) The variability between observers is small when expressed in terms
      of perceptual errors, which is consistent with the hypothesis that the colour
      vision system in adult humans is able to recalibrate itself based on prior visual
      experience.

PMID- 16087210
TI  - Greater losses in sensitivity to second-order local motion than to first-order
      local motion after early visual deprivation in humans.
AB  - We compared sensitivity to first-order versus second-order local motion in
      patients treated for dense central congenital cataracts in one or both eyes.
      Amplitude modulation thresholds were measured for discriminating the direction of
      motion of luminance-modulated (first-order) and contrast modulated (second-order)
      horizontal sine-wave gratings. Early visual deprivation, whether monocular or
      binocular, caused losses in sensitivity to both first- and second-order motion,
      with greater losses for second-order motion than for first-order motion. These
      findings are consistent with the hypothesis that the two types of motion are
      processed by different mechanisms and suggest that those mechanisms are
      differentially sensitive to early visual input.

PMID- 16087211
TI  - Comparison of selected non-exhaustive extraction techniques to assess PAH
      availability in dissimilar soils.
AB  - Recently, it has become apparent that the use of total contaminant concentrations
      as a measure of potential contaminant exposure to plants or soil organisms is
      inappropriate and that bioavailability of contaminants is a better measure of
      potential exposure. In light of this, non-exhaustive extraction techniques are
      being investigated to assess their appropriateness in determining
      bioavailability. In this study, phenanthrene extractability using hydroxypropyl
      beta-cyclodextrin (HPCD) and desorption kinetics using butan-1-ol (BuOH) were
      determined in three dissimilar spiked soils. The soils were extracted after 1 d,
      40 d and 80 d of soil-compound contact time. The amount of phenanthrene extracted
      by HPCD was compared to the rapidly desorbed fraction removed by BuOH. Further
      experiments using the same soils and extraction methods to assess the relative
      extractability of phenanthrene, pyrene and benzo(a)pyrene were conducted.
      Overall, the extraction methods used in this study had different extraction
      efficiencies. Results suggest that as compound hydrophobicity increased, BuOH
      became a more exhaustive extractant with respect to HPCD, especially for soils
      with high clay and organic matter content. These results are important as they
      highlight differences between two contrasting non-exhaustive extraction
      techniques both of which have been suggested to be appropriate in the assessment
      of bioavailability.

PMID- 16087212
TI  - Measurement of 224Ra uptake in a fern actively accumulating radium.
AB  - A method is proposed for determining the level of 224Ra in plant samples by
      measuring its descendant nuclide 212Pb at 239 keV by gamma-ray spectrometry.
      Variations of 224Ra and 212Pb over time during sample preparation and counting
      were delineated prior to gamma-ray measurement. The 224Ra concentrations in plant
      samples were measured by their direct uptake from soil, which could be determined
      and distinguished from that resulting from decay of 228Th inside the plants. We
      propose that a field-growing Dicranopteris linearis, which actively accumulates
      radium, can be used as an indicator of the nutritional transportation and
      metabolic rate of radium and other alkaline earth elements. We investigated the
      influence of rainfall on 224Ra concentrations in fronds of D. linearis and the
      corresponding uptake rates. 224Ra could serve as a natural tracer of growth in
      plants over a several days. Its presence and content in plants implies a temporal
      mineral metabolic rate, which can provide useful information for plant
      physiological and environmental investigations.

PMID- 16087213
TI  - Role of cyanobacteria in the biodegradation of crude oil by a tropical
      cyanobacterial mat.
AB  - Cyanobacterial mats are ubiquitous in tropical petroleum-polluted environments.
      They form a high biodiversity microbial consortium that contains efficient
      hydrocarbons degraders. A cyanobacterial mat collected from a petroleum
      contaminated environment located in Indonesia was studied for its biodegradation
      potential. In the field, the natural mat was shown to degrade efficiently the
      crude oil present in the environment. This natural mat demonstrated also a strong
      activity of degradation on model crude oil under laboratory conditions. In axenic
      cultures, the monospecific cyanobacterium Phormidium animale that constitute the
      bulk of the biomass did not exhibit any degradative capacity on hydrocarbons in
      the range of C13-C35 carbon atom number either in autotrophic or heterotrophic
      conditions. It was concluded that this cyanobacterial strain living on a heavily
      contaminated site had no direct effect on biodegradation of crude oil, the
      degradation activity being exclusively achieved by the other microorganisms
      present in the microbial consortium of the mat.

PMID- 16087214
TI  - Chemical characterization of fine particles from on-road vehicles in the Wutong
      tunnel in Shenzhen, China.
AB  - Vehicle populations in China have been increasing sharply since 1990s. Vehicle
      emissions including various gaseous pollutants and particulate matter cause
      deterioration of air quality. However, measurements of particulate mater from on
      road vehicles in China are scarcely reported, and thus the chemical compositions
      of particles emitted from vehicles in China are unknown. In this research, tunnel
      experiments were performed to measure PM2.5 in the Wutong tunnel, Shenzhen,
      China. Detailed PM2.5 chemical compositions, with organic compounds determined by
      GC/MS, in the tunnel were presented. Elemental carbon and organic matter composed
      63% and 34% of the total PM2.5 mass in the Wutong tunnel, respectively. Alkanes,
      PAHs, hopanes, fatty acids, and dicarboxylic acids were the major identified
      organic compounds, and their source profiles in the PM2.5 in the Wutong tunnel
      were characterized. The comparisons of our measurements with those in the
      literature were also made to demonstrate the characteristics of the vehicle
      source profiles in the Wutong tunnel. The experimental results in this paper can
      improve understanding of particulate matter emitted from vehicles in China.

PMID- 16087215
TI  - Comparison of AC/O3-BAC and O3-BAC processes for removing organic pollutants in
      secondary effluent.
AB  - AC (activated carbon)/O3-BAC (biological activated carbon) process was employed
      to treat secondary effluent and compared to O3-BAC process. The effects of ozone
      dosages and empty bed contact time (EBCT) in BAC on dissolved organic carbon
      (DOC) removal were investigated. The results showed that the presence of AC
      improved ozone utilization and biodegradability of the effluent. DOC removal
      increased with ozone dosage and EBCT in BAC, however, 3 mg l(-1) ozone dosage
      with 15 min oxidation time and 15 min EBCT in BAC were more economical and
      efficient. For DOC removal, AC/O3-BAC was more efficient than O3-BAC and its
      synergetic effect was more than that in O3-BAC process. The biomass of the
      subsequent BAC unit in AC/O3-BAC process was more than that in O3-BAC process and
      much more than that in BAC alone. Except for organic pollutants with molecular
      weight (MW) >10 kDa, those of other MW range were decomposed much more by AC/O3
      process than by O3 process. GC/MS analysis showed that dibutyl phthalate, bis(2
      ethylhexyl) phthalate, 4-bromo-3-chloroaniline, 2-propanone-ethylhydrazone and
      phenol derivatives were prevalent organic compounds in the secondary effluent.
      Some aromatic compounds, such as 4-bromo-3-chloroaniline and 2,4-dichloro
      benzenamine disappeared after AC/O3 treatment. However, some small molecules were
      generated, after further biological treatment by BAC, the kinds and concentration
      of organic compounds were greatly reduced.

PMID- 16087216
TI  - Effects of zero-valent iron (Fe0) and temperature on the transformation of DDT
      and its metabolites in lake sediment.
AB  - Zero-valent iron improves the transformation of DDT [1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane] and its metabolites in aged and highly contaminated lake
      sediment under biotic conditions. The addition of Fe0 has a strong effect on
      transformation rates at 22 degrees C and 9 degrees C, the most enhanced
      degradation being obtained for DDT and DDOH [2,2-bis(p-chlorophenyl)ethanol]. At
      22 degrees C and 10 weeks' incubation, the DDT concentration is reduced from 2.75
      micromol g(-1) (974 mg kg(-1)) to 0.98 micromol g(-1) (346 mg kg(-1)) and 1.98
      micromol g(-1) (702 mg kg(-1)) in samples with and without the addition of iron,
      respectively. After 40 weeks' incubation these concentrations have further
      decreased to 0.19 micromol g(-1) (66 mg kg(-1)) and 0.74 micromol g(-1) (264 mg
      kg(-1)). There is no significant transformation of any of the compounds at 9
      degrees C without the addition of Fe0. In the presence of iron, however, DDT is
      reduced to 1.25 micromol g(-1) (442 mg kg(-1)) within 40 weeks' incubation. This
      study demonstrates the ability of adapted microorganisms to transform DDT under
      elevated temperatures in original, aged sediments, and also the stimulating
      effect of zero-valent iron, which is significant even at low temperatures.

PMID- 16087217
TI  - Generation of reversible Rb-knockdown mice.
AB  - This study describes the generation of reversible Rb-knockdown mice using Tet-off
      system coupled with Rb-deficient mice currently available. Mice expressing pRB
      conditionally in Rb-/- background were generated by crossings P(hCMV)-tTA/TRE-Rb
      transgenic mice with conventional Rb+/- mice. Transgenic Rb was tightly
      controlled with reversibility and biologically effective as exemplified by cyclin
      E expression in a doxycycline-dependent manner in mouse embryonic fibroblasts.
      However, its ectopic expression was not sufficient to rescue the phenotypes of Rb
      /- embryos at organismal level, suggesting the requirement of more sophisticated
      regulation of pRB. With all, these results demonstrate that our experimental
      strategy can be an alternative way to convert classical gene-disrupted mice into
      reversible conditional ones.

PMID- 16087218
TI  - Antioxidants do not explain the disparate longevity between mice and the longest
      living rodent, the naked mole-rat.
AB  - The maximum lifespan of naked mole-rats (NMRs; Heterocephalus glaber) is greater
      than that of any other rodent. These hystricognaths survive in captivity >28
      years, eight-times longer than similar-sized mice. The present study tested if
      NMRs possess superior antioxidant defenses compared to mice and if age-related
      interspecies changes in antioxidants were evident. Activities of Cu/Zn superoxide
      dismutase (Cu/Zn, SOD), Mn SOD, catalase and cellular glutathione peroxidase
      (cGPx) were measured in livers of physiologically equivalent age-matched NMRs
      (30, 75 and 130 months) and CB6F1 mice (4, 12 and 18 months). In mice, Mn SOD
      activity increased with age, while the activity of catalase and cGPx declined.
      None of the antioxidants changed with age in mole-rats. cGPx activity of NMRs was
      70-times lower (p < 0.0001) than in mice, and resembled that of cGPx knock-out
      animals. NMRs may partially compensate for the lower cGPx when compared to mice,
      by having moderately higher activities of the other antioxidants. It is
      nonetheless unlikely that antioxidant defenses are responsible for the eight-fold
      longevity difference between these two species. Maintenance of constant
      antioxidant defenses with age in NMRs concurs with previous physiological data,
      suggesting delayed aging in this species.

PMID- 16087219
TI  - LRRK2 mutations are not common in Alzheimer's disease.
AB  - The development of common age-related neurodegenerative disorders as Parkinson's
      disease and Alzheimer's disease (AD) are influenced by genetic factors. Recently,
      pathogenic mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been
      identified in familial Parkinsonism. Individuals in some of these families
      developed symptoms of dementia with Lewy-bodies and AD. The LRRK2 gene is also
      located within a locus on chromosome 12 reported in late-onset AD, and is
      therefore a good candidate gene for dementia. A series of 242 patients from
      Norway diagnosed clinically with dementia were included in the study, the
      majority were diagnosed with AD. Individuals were screened for the presence of
      seven known pathogenic mutations previously reported in the LRRK2 gene. We did
      not identify LRRK2 mutations in our series of dementia patients, indicating that
      known pathogenic mutations are not common in patients clinically diagnosed with
      AD. However, these results do not exclude a possible role of other genetic
      variants within the LRRK2 gene in AD or other forms of dementia.

PMID- 16087220
TI  - Cellular dynamics and modulation of WRN protein is DNA damage specific.
AB  - The human premature aging protein Werner (WRN), deficient in Werner syndrome
      (WS), is localized mainly to the nucleolus in many cell types. DNA damage or
      replication arrest causes WRN to redistribute from the nucleolus to the
      nucleoplasm into discrete foci. In this study, we have investigated DNA damage
      specific cellular redistribution of WRN. In response to agents causing DNA double
      strand breaks or DNA base damage, WRN is re-distributed from the nucleolus to the
      nucleoplasm in a reversible manner. However, after ultraviolet (UV) irradiation
      such redistribution of WRN is largely absent. We also show that WRN is associated
      with the insoluble protein fraction of cells after exposure to various kinds of
      DNA damage but not after UV irradiation. Further, we have studied the DNA damage
      specific post-translational modulation of WRN. Our results show that WRN is
      acetylated after mytomycin C or methyl methane-sulfonate treatment, but not after
      UV irradiation. Also, DNA damage specific phosphorylation of WRN is absent in UV
      irradiated cells. Inhibition of phosphorylation fails to restore WRN
      localization. Thus, our results suggest that the dynamics of WRN protein
      trafficking is DNA damage specific and is related to its post-translational
      modulation. The results also indicate a preferred role of WRN in recombination
      and base excision repair rather than nucleotide excision repair.

PMID- 16087223
TI  - Pregnane X receptor: predicting and preventing drug interactions.

PMID- 16087221
TI  - Aging alters vascular mechanotransduction: pressure-induced regulation of p70S6k
      in the rat aorta.
AB  - Physical forces are important regulators of vascular structure and function
      though it is unknown how aging may affect the ability of the vasculature to
      respond to mechanical stimuli. We investigated the pressure-induced activation of
      ribosomal S6-kinase (p70S6k) and its pathway-related proteins (Akt, GSK-3beta,
      SHP-2, PTEN) in aortae from young adult (6 month), aged (30 month), and very aged
      (36 month) Fischer 344 x Brown Norway F1 hybrid rats. With aging, the aortic
      tissue content of Akt. SHP-2, and PTEN was significantly increased while total
      p70S6k and GSK-3beta were unchanged. By comparison, the basal phosphorylation of
      p70S6k at Thr 389 and Thr 421/Ser 424 was increased ( approximately 40%) and
      unchanged, respectively, while Akt decreased (approximately 37%), GSK-3beta was
      unchanged, SHP-2 increased (approximately 73.5%), and PTEN increased
      (approximately 120%) in the aortae of very aged rats. Acute pressurization of
      aortae resulted in similar increases in phosphorylation of Akt among the
      different age groups. By comparison, pressure-induced phosphorylation of p70S6k
      at Thr 389, GSK-3beta and SHP-2 decreased; whereas, PTEN dephosphorylation was
      increased in 36-month versus 6-month aortae. The results indicate marked
      alterations in the p70S6k signaling pathway with aging. The implications of these
      findings on age-associated vessel remodeling are discussed.

PMID- 16087224
TI  - Agrammatic sentence production: is verb second impaired in Dutch?
AB  - This study investigates effects of verb movement in nine Dutch-speaking
      agrammatic aphasics. According to linguistic theory, in verb second languages
      such as Dutch and German, the verb remains in its clause-final base position in
      embedded clauses, whereas it moves to second position in main clauses. In recent
      linguistic accounts of agrammatic sentence production, it has been suggested that
      the production of sentences with moved verbs is relatively difficult. However, we
      argue that evidence provided by previous studies on this matter is inconclusive.
      An experiment is reported in which the production of both types of clauses is
      compared. No evidence is found that sentences with moved verbs are relatively
      difficult to produce. In fact, there was a tendency for the base order sentences
      to be harder. Implications of these findings for theories of normal and
      agrammatic sentence production are discussed.

PMID- 16087225
TI  - Hygroscopic and hydrolytic effects in dental polymer networks.
AB  - OBJECTIVES: The objective of this manuscript is to outline the factors associated
      with hygroscopic and hydrolytic effects in dental polymer networks, and to review
      the literature generated over the past thirty years or more in this area.
      METHODS: Information was gathered from nearly 90 published articles or abstracts
      appearing in the dental and polymer literature. Studies were predominantly
      identified through a search of the PubMED database. RESULTS: Studies were
      included that provided direct evidence for the uptake of solvent by a polymer
      network and its subsequent physical or chemical effect, or the loss of molecular
      species into solvents. An attempt was made to select articles that spanned the
      timeframe from approximately 1970 to today to ensure that most of the classic
      literature as well as the latest information was included. CONCLUSIONS: Dental
      polymer networks have been shown to be susceptible to hygroscopic and hydrolytic
      effects to varying extents dependent upon their chemistry and structure. The
      importance of these effects on the clinical performance of polymer restoratives
      is largely unknown, though numerous investigators have alluded to the potential
      for reduced service lives. SIGNIFICANCE: While the physical and mechanical
      properties of these materials may be significantly altered by the effects of
      solvent uptake and component elution, what may constitute the greatest concern is
      the short-term release of unreacted components and the long-term elution of
      degradation products in the oral cavity, both of which should be strongly
      considered during restorative material development.

PMID- 16087226
TI  - Fluoride release from dental cements and composites: a mechanistic study.
AB  - OBJECTIVES: The purpose of this study was (1) to compare the fluoride release
      profile of an experimental composite to commercial GICs, resin-modified GICs, and
      composite resins; (2) to assess the fluoride release process. METHODS: Commercial
      materials (n = 3) were prepared according to manufacturers' directions. The
      experimental composite (n = 3) consisted of 78 wt% filler and 22 wt% resin. The
      resin consisted of 19 wt% BisGMA, 38 wt% UDMA, 19 wt% TEGDMA, and 24 wt% HEMA.
      Disc specimens were placed into 25 ml of deionized water in sealed polyethylene
      vials and shaked at 1.4 Hz at 37 degrees C. Fluoride release was measured using a
      fluoride-ion specific electrode at different time intervals up to 284 days.
      RESULTS: The fluoride release rate of the experimental composite demonstrated the
      highest rate of release within the first day (p = 0.05), but decreased
      significantly by day 7. Release rates of the commercial glass-ionomer cements and
      resin-modified glass-ionomer cements thereafter were significantly higher than
      the experimental and commercial composites at p = 0.05. Among the materials
      studied, cumulative fluoride release is adequately described by a two-term
      equation consisting of an initial fluoride release via a rapid dissolution
      process followed by a long-term diffusive release. SIGNIFICANCE: An increase in
      the hydrophilicity of the polymer matrix through the introduction of HEMA
      improved the fluoride release over the short term during which dissolution
      occurs. Such a release behavior could be beneficial if it results in a fluoride
      reservoir that could be maintained by a prolonged slower release thereafter.

PMID- 16087228
TI  - Influence of the antagonist material on the wear of different composites using
      two different wear simulation methods.
AB  - OBJECTIVES: The aim of the study was to evaluate two ceramic materials as
      possible substitutes for enamel using two wear simulation methods, and to compare
      both methods with regard to the wear results for different materials. METHODS:
      Flat specimens (OHSU n=6, Ivoclar n=8) of one compomer and three composite
      materials (Dyract AP, Tetric Ceram, Z250, experimental composite) were fabricated
      and subjected to wear using two different wear testing methods and two pressable
      ceramic materials as stylus (Empress, experimental ceramic). For the OHSU method,
      enamel styli of the same dimensions as the ceramic stylus were fabricated
      additionally. Both wear testing methods differ with regard to loading force,
      lateral movement of stylus, stylus dimension, number of cycles, thermocycling and
      abrasive medium. In the OHSU method, the wear facets (mean vertical loss) were
      measured using a contact profilometer, while in the Ivoclar method (maximal
      vertical loss) a laser scanner was used for this purpose. Additionally, the
      vertical loss of the ceramic stylus was quantified for the Ivoclar method. The
      results obtained from each method were compared by ANOVA and Tukey's test
      (p<0.05). To compare both wear methods, the log-transformed data were used to
      establish relative ranks between material/stylus combinations and assessed by
      applying the Pearson correlation coefficient. RESULTS: The experimental ceramic
      material generated significantly less wear in Tetric Ceram and Z250 specimens
      compared to the Empress stylus in the Ivoclar method, whereas with the OHSU
      method, no difference between the two ceramic antagonists was found with regard
      to abrasion or attrition. The wear generated by the enamel stylus was not
      statistically different from that generated by the other two ceramic materials in
      the OHSU method. With the Ivoclar method, wear of the ceramic stylus was only
      statistically different when in contact with Tetric Ceram. There was a close
      correlation between the attrition wear of the OHSU and the wear of the Ivoclar
      method (Pearson coefficient 0.83, p=0.01). SIGNIFICANCE: Pressable ceramic
      materials can be used as a substitute for enamel in wear testing machines.
      However, material ranking may be affected by the type of ceramic material chosen.
      The attrition wear of the OHSU method was comparable with the wear generated with
      the Ivoclar method.

PMID- 16087227
TI  - Surface analysis of porcelain fused to metal systems.
AB  - OBJECTIVE: The effect of four different, commonly performed, metal-ceramic alloy,
      surface preparation stages, were investigated to observe surface compositional
      changes. METHODS: Two metal-ceramic alloys were examined (Pd/Ag alloy and a Ni/Cr
      alloy). Discs 12 mm diameter and 2mm thick were produced using the lost wax
      casting process. Prior to casting alloy ingots were examined using X-ray
      fluorescence spectrometry (XRF) to determine bulk composition. The four
      preparation stages were (1) devesting and Al2O3 blasted; (2) ground smooth and
      Al2O3 blasted; (3) oxidation firing; (4) firing cycle for opaque porcelain
      application. X-ray photoelectron spectroscopy (XPS) surface analysis was
      performed after each surface preparation stage to determine changes in surface
      composition. SEM with EDS was also used to identify surface composition. RESULTS:
      XRF and manufacturers compositional analysis of the alloys showed similar
      findings for the major elements. XPS analysis showed that at preparation stages 3
      and 4 evidence of elemental migration to the surface (In with Pd/Ag alloy and Cr
      and Mn with Ni/Cr alloy). Alumina was also seen on the alloy surfaces, with
      SEM/EDS confirming Al2O3 particles embedded in the surface of the alloys.
      SIGNIFICANCE: Surface composition is very different from the batch composition.
      Surface preparation stage 3 is essential in bringing to the alloy surface
      elements which could be directly involved in the metal-ceramic bond. Elements and
      their oxides, in various forms, cover the surface of the alloys. Al2O3 particles
      can remain embedded in the alloy surface during porcelain application.

PMID- 16087229
TI  - In vitro cytotoxicity of a remineralizing resin-based calcium phosphate cement.
AB  - Recently, a resin-based calcium phosphate cement (RCPC) has been reported as a
      remineralizing pulp-capping or lining cement. RCPC consists mainly of
      tetracalcium and dicalcium phosphates, ethoxylated bisphenol A dimethacrylate and
      pyromellitic glycerol dimethacrylate monomers and photo- and chemical initiators.
      OBJECTIVES: Here, the cytotoxic effects of RCPC were evaluated. The hypothesis
      was that RCPC induced only minor cytotoxic response in immortalized murine
      odontoblast and pulp cells, comparable to that produced by similar
      dimethacrylates due to unpolymerized dimethacrylate monomer present after curing.
      METHODS: Cytotoxicity was determined following the changes in cell succinate
      dehydrogenase activity after 24 h exposure to the cement components and after a
      24 h recovery period. A fourfold range of concentrations was tested of the
      monomers, the eluate of cured RCPC leached in Dulbecco's modified Eagle's medium,
      and crushed cured cement in dimethyl sulfoxide. RESULTS: The monomers themselves
      had cytotoxicities similar to those reported for other dimethacrylates, although
      they are significantly less toxic than Bis-GMA. Differential cell sensitivity was
      demonstrated, with the pulp cells having greater sensitivity to the unpolymerized
      monomer than the odontoblast-like cells. The leached components have cytotoxicity
      similar to that of the free monomers. The crushed material demonstrated no
      apparent cytotoxicity at the dilutions tested. SIGNIFICANCE: These data
      demonstrate that RCPC has an in vitro cytotoxicity that is comparable to other
      materials containing dimethacrylate monomers and suggest that the material may be
      suitable for use in dental restorations. The data also indicate that the pulp
      cells appear more sensitive to dimethacrylates than the odontoblasts.

PMID- 16087230
TI  - The effect of carotenoids obtained from saffron on histone H1 structure and H1
      DNA interaction.
AB  - It is already known that transcriptional activation of genes occurs due to the H1
      dissociation from linker DNA; hence, histone H1-DNA complex is considered as a
      model of chromatin. Anticancer property of saffron and its carotenoids has
      already been reported. The present study aimed at investigating the effect of
      saffron carotenoids on H1 structure and H1-DNA interaction as a possible
      mechanism of their anticarcinogenic action. After purification of the saffron
      carotenoids (crocin, crocetin and dimethylcrocetin), their interaction with
      histone H1 was studied using spectrophotometry and spectrofluorometry. Some
      changes on the absorption spectra of H1 indicated the complex formation between
      this protein and saffron carotenoids. Also, the fluorescence emission of H1 was
      quenched by the mentioned ligands. The binding parameters of all the three
      ligands were obtained through Schatchard analysis of the quenching data. Then,
      the effect of each ligand on the H1-DNA interaction was studied. The results
      showed a shift in the precipitation curve to the left in the presence of the
      mentioned carotenoids, which is due to the reduction in the interaction of H1
      with DNA. These observations led to the suggesting a mechanism in which the H1
      depletion may promote transcription.

PMID- 16087231
TI  - Endoplasmic reticulum stress response and neurodegeneration.
AB  - The endoplasmic reticulum (ER) is a subcellular compartment playing a central
      role in calcium storage and signaling. Disturbances of ER calcium homeostasis
      constitute a severe form of stress interfering with central functions of this
      structure including the folding and processing of newly synthesized membrane and
      secretory proteins. Blocking the folding and processing reactions results in the
      accumulation of unfolded proteins forming potentially toxic aggregates. To
      restore ER functioning, specific stress responses are activated one of which is
      the unfolded protein response (UPR). UPR is characterized by a shutdown of global
      protein synthesis and activation of expression of genes coding for ER-resident
      proteins that are involved in the folding and processing reactions. ER calcium
      homeostasis is therefore inevitably associated with major cellular functions,
      including gene transcription and translation. ER calcium homeostasis und ER
      functions are believed to be impaired in various degenerative diseases of the
      brain including Alzheimer's, Parkinson's and Huntington's disease, and
      amyotrophic lateral sclerosis. ER functioning has also been shown to be disturbed
      in acute pathological states of the brain such as ischemia and trauma, which have
      been identified as risk factors for the development of degenerative diseases.
      This implies that there are common underlying pathomechanisms. This review will
      summarize new observations suggesting that impairment of ER functioning may be a
      common denominator of pathological processes resulting in neuronal cell injury in
      acute disorders and degenerative diseases of the brain.

PMID- 16087232
TI  - Mitochondria and calcium signaling.
AB  - The kinetic properties for the uptake, storage and release of Ca2+ from isolated
      mitochondria accurately predict the behaviour of the organelles within the intact
      cell. While the steady-state cycling of Ca2+ across the inner membrane between
      independent uptake and efflux pathways seems at first sight to be symmetrical,
      the distinctive kinetics of the uniporter, which is highly dependent on external
      free Ca2+ concentration and the efflux pathway, whose activity is clamped over a
      wide range of total matrix Ca2+ by the solubility of the calcium phosphate
      complex provide a mechanism whereby mitochondria reversibly sequester transient
      elevations in cytoplasmic Ca2+. Under non-stimulated conditions, the same
      transport processes can regulate matrix Ca2+ concentrations and hence citric acid
      cycle activity.

PMID- 16087233
TI  - Functional specializations within the tectum defense systems of the rat.
AB  - Here we review the differential contribution of the periaqueductal gray matter
      (PAG) and superior colliculus (SC) to the generation of rat defensive behaviors.
      The results of studies involving sine-wave and rectangular pulse electrical
      stimulation and chemical (NMDA) stimulation are summarized. Stimulation of SC and
      PAG produced freezing and flight behaviors along with exophthalmus (fully opened
      bulged eyes), micturition and defecation. The columnar organization of the PAG
      was evident in the results obtained. Defecation was elicited primarily by lateral
      PAG stimulation, while the remaining defensive behaviors were similarly elicited
      by lateral and dorsolateral PAG stimulation, although with the lowest thresholds
      in the dorsolateral column. Conversely, the ventrolateral PAG did not appear to
      participate in unconditioned defensive behaviors, which were only elicited by
      high intensity stimulation likely to encroach on adjacent regions. In the SC, the
      most important differences relative to the PAG were the lack of stimulation
      evoked jumping in both intermediate and deep layers, and of NMDA-evoked galloping
      in intermediate layers. Therefore, we conclude that the SC may be only involved
      in the increased attentiveness (exophthalmus, immobility) and restlessness
      (trotting) of prey species exposed to the cues of a nearby predator. These
      responses may be distinct from the full-blown flight reaction that is mediated by
      the dorsolateral and lateral PAG. However, other evidences suggest the possible
      influences of stimulation schedule, environment dimensions and rat strain in
      determining outcomes. Overall our results suggest a dynamically organized
      representation of defensive behaviors in the midbrain tectum.

PMID- 16087234
TI  - Snaphots of 19th-century science.

PMID- 16087235
TI  - DNA fingerprinting on trial: the dramatic early history of a new forensic
      technique.
AB  - The early history of "DNA fingerprinting" in the UK might have been different
      were it not for the accounts of two dramatic courtroom trials, made by the
      participants and the media, in the mid-1980s. But these reports, which
      misrepresented the importance DNA evidence had in the trials, left a strong
      impression on the British public and on judges on both sides of the Atlantic.
      These trials, widely considered to be the first "victories" for DNA
      fingerprinting, have been frequently cited as proof of the utility and
      reliability of the technique, in both the UK and beyond. But in reality, it was
      the threat of DNA evidence being used rather than the integrity or validity of it
      that resolved these cases. At that time, DNA fingerprinting was still in its
      infancy, an untried and untested technology.

PMID- 16087236
TI  - Wartime rat control, rodent ecology, and the rise and fall of chemical
      rodenticides.
AB  - The story of how World War II stimulated the development of DDT, and the ensuing
      postwar dependence on such chemical insecticides, is well known. However, less
      recognition has been given to the wartime efforts to synthesize new rodenticides
      to fight rat-borne epidemics. Baltimore, Maryland served as the site for field
      tests of the powerful new compound alpha naphthyl thiourea (ANTU) from 1942-1946.
      This experimental campaign sparked debates over the efficacy of controlling rats
      via chemical warfare instead of environmental sanitation, which led to the ironic
      conclusion that urban rat control demanded an ecological, rather than
      technological, approach.

PMID- 16087237
TI  - Validation of in silico prediction by in vitro immunoserological results of fine
      epitope mapping on citrate synthase specific autoantibodies.
AB  - In silico antibody-antigen binding predictions are generally employed in research
      to rationalize epitope development. These techniques are widely spread despite
      their technical limitations. To validate the results of these bioinformatic
      calculations evidence based comparative in vitro studies are necessary. We have
      used a well-conserved mitochondrial inner membrane antigen-citrate synthase to
      develop a model for comparative analysis of the predicted and the
      immunoserologically verified epitopes of circulating autoantibodies. Epitopes
      were predicted using accepted tools: the GCG Wisconsin package and TEPITOPE 2000.
      An overlapping multipin ELISA assay--covering 49% of the citrate synthase
      molecule--was developed to map autoantibody epitopes of individuals (healthy,
      systemic autoimmune, and heart transplanted) in different immunopathological
      conditions. From the 40 synthesized decapeptides 34 were predicted in silico and
      27 were validated in vitro. Thirty-two percent of epitopes were recognized by
      majority of sera 47% by at least one sera. False positive predictions were 21%.
      There was major difference in the recognized epitope pattern under different
      immunopathological conditions. Our results suggest that special databases are
      needed for training and weighing prediction methods by clinically well
      characterized samples, due to the differences in the immune response under
      different health status. The development of these special algorithms needs a new
      approach. A high number of samples under these special immunological conditions
      are to be mapped and then used for the "fine tuning" of different prediction
      algorithms.

PMID- 16087238
TI  - Endocanalicular laser dacryocystorhinostomy analysis of 118 consecutive
      surgeries.
AB  - PURPOSE: To describe the outcomes of endocanalicular laser dacryocystorhinostomy
      (ECL DCR) for patients with nasolacrimal duct obstruction (NLDO). DESIGN:
      Retrospective, noncomparative, interventional case series. PARTICIPANTS: One
      hundred eight consecutive patients who underwent ECL DCR. METHODS: The records of
      the patients who underwent ECL DCR at 1 of 2 academic centers were reviewed and
      the data analyzed. MAIN OUTCOME MEASURES: Success was defined as the resolution
      of symptoms or unobstructed lacrimal irrigation. RESULTS: One hundred eighteen
      consecutive ECL DCR surgeries performed on 108 patients between June 1997 and
      June 2003 were reviewed, excluding 6 lost to follow-up. Endocanalicular laser DCR
      was the initial surgical intervention for all cases except 6 that had previously
      undergone surgery (external or endonasal DCR) at outside hospitals. Twenty-seven
      of the surgeries were considered failures on the basis of recurrent epiphora or
      discharge, or reflux on nasolacrimal irrigation. One of the failures was
      permanently corrected with balloon dacryoplasty. Nine of the other failures had a
      repeat procedure, with 7 remaining patent after one repeat procedure and an
      additional one remaining patent after a third procedure. All 6 ECL DCR procedures
      that were performed after external or endonasal DCR at an outside institution
      remained patent. Among the 102 initial lacrimal surgeries in this series, there
      was a 73.6% success rate. The overall success, including repeat procedures, was
      81.5%. The success of this technique as a repeat procedure after previous
      external, endonasal, or ECL DCRs was 87.5%. CONCLUSIONS: Endocanalicular laser
      DCR offers a minimally invasive alternative procedure for the treatment of NLDO.
      In our series, the success rates are comparable to those previously reported. The
      technique had a high success rate when used to treat recurrent NLDO after
      previous lacrimal surgery.

PMID- 16087239
TI  - Preferred retinal locus development in patients with macular disease.
AB  - OBJECTIVE: To observe the development of the preferred retinal locus (PRL) in a
      group of patients with central scotomas caused by recent onset macular disease
      (MD). DESIGN: Prospective observational case series. PARTICIPANTS: Twenty-five
      individuals with bilateral central scotomas caused by MD. All patients had
      experienced visual loss in their better eye in the 2 weeks before recruitment.
      METHODS: Patients were assessed at baseline and at 4 further visits for up to 12
      months. At each visit, the retinal area used for fixation was assessed using a
      scanning laser ophthalmoscope, the infrared Gazetracker was used to determine the
      number of discrete retinal areas used for fixation in 5 positions of gaze, and
      reading speed was measured using MN-Read-style sentences. RESULTS: All 25
      patients developed a PRL within 6 months. Sixteen patients (64%) made an
      adaptation whereby they were unaware of using an eccentric retinal area for
      fixation. Multiple fixation loci were exhibited by 11 patients at the end of the
      study. Nineteen patients used a consistent number of PRLs under all positions of
      gaze. Reading speed was not associated with PRL location or the presence of
      multiple PRLs. CONCLUSIONS: All of the patients in this study developed a
      repeatable preferred retinal locus within 6 months of visual loss in their second
      affected eye. Reading performance was better in patients who were not aware of
      using eccentric viewing strategies and who used a repeatable number of PRLs under
      all positions of gaze. These findings are relevant for counseling patients with
      MD and for the design of rehabilitation programs for patients with central vision
      loss.

PMID- 16087240
TI  - Activation of monoamine oxidase isotypes by prolonged intake of aluminum in rat
      brain.
AB  - Rats were fed 100 microM aluminum maltolate for one year in their drinking water.
      Brain aluminum contents have increased 4.2-fold in the aluminum-treated group,
      whereas no significant changes in the body weight, brain weight, and brain
      protein content were observed. Long-term aluminum feeding induced apoptosis as
      assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling method and showed activatory effects on the catalytic efficiency
      (kcat/KM) of monoamine oxidase-A and monoamine oxidase-B up to 1.9- and 3.8-fold,
      respectively. The expression level of monoamine oxidase isotypes on the Western
      blot remained unchanged between the two groups, suggesting a change in post
      translational regulation of the activities of monoamine oxidase isotypes by long
      term aluminum feeding.

PMID- 16087241
TI  - Metals accelerate the formation and direct the structure of amyloid fibrils of
      NAC.
AB  - Non-beta amyloid component of Alzheimer's disease amyloid or NAC is a highly
      amyloidogenic peptide consisting of 35 amino acids which was first identified
      associated with senile plaques in the Alzheimer's disease brain. It is a fragment
      of the presynaptic protein alpha-synuclein and, as such, it is implicated in the
      aetiologies of both Alzheimer's (AD) and Parkinson's (PD) disease. Metals are
      involved in the aggregation of amyloidogenic peptides such as beta amyloid
      (Abeta), British amyloid peptide (ABri) and alpha-synuclein though nothing is yet
      known about how they might influence the aggregation of NAC. We show herein that
      NAC will form beta-pleated conformers at a peptide concentration of only 2.0
      microM and that metals, and Zn(II) and Cu(II) in particular, accelerate the
      formation of these fibrils. Cu(II) and Zn(II) did not influence the diameter or
      general structure of the fibrils which were formed though many more shorter
      fibrils were observed in their presence and these shorter fibrils were highly
      thioflavin T positive and they were efficient catalysts of the redox cycling of
      added Fe(II). By way of contrast, beta-pleated conformers of NAC which were
      formed in the presence of Al(III) showed much lower levels of thioflavin T
      fluorescence and were poorer catalysts of the redox cycling of added Fe(II) and
      these properties were commensurate with an increased abundance of a novel amyloid
      morphology which consisted of twisted fibrils with a periodicity of about 100 nm.
      These spirals of twisted fibrils were especially abundant in the presence of
      added Al(III) and it is speculated that NAC binding of Al(III) may be important
      in their formation and subsequent stability.

PMID- 16087242
TI  - Synthesis, structure, and reactivity of monofunctional platinum(II) and
      palladium(II) complexes containing the sterically hindered ligand 6
      (methylpyridin-2-yl)acetate.
AB  - Three complexes containing the novel, sterically hindered ligand 6-(methylpyridin
      2-yl)acetate (PICAC) have been synthesized and characterized: [Pt(NH3)2(PICAC
      N,O)]NO3 (1), [Pt(en)(PICAC-N,O)]NO3 (2), and [Pd(en)(PICAC-N,O)]NO3 (3) (en =
      ethane-1,2-diamine). The crystal structures of 2 and 3 have been determined. The
      two complexes are isostructural and exhibit a mixed [N3O] coordination. In both
      cases, PICAC forms a sterically crowded six-membered chelate. Signal
      multiplicities in 1H NMR spectra of 1-3 indicate that the N,O chelates are
      conformationally rigid on the NMR timescale as a result of the steric bulk of the
      pyridine derivative. Complex 2 undergoes facile ring opening in 0.1M NaCl
      solution at neutral pH, resulting in a zwitterionic species in which carboxylate
      oxygen has been replaced with chloride. The complex was identified by X-ray
      crystallography as [PtCl(en)(PICAC-N)] x H2O (4), which contains a "dangling"
      carboxylate group. In 4, the pyridine moiety adopts an almost perpendicular
      orientation relative to the platinum coordination plane. Likewise, complex 2
      reacts rapidly with 5'-guanosine monophosphate (5'-GMP) to form the
      monofunctional adduct [Pt(en)(PICAC)(5'-GMP)] (5) (NMR, 25 degrees C, t(1/2)
      approximately 24 min). 2-D nuclear Overhauser enhancement spectroscopy (NOESY)
      and double quantum-filtered correlated spectroscopy (dqf-COSY) experiments (500
      MHz) and variable temperature NMR spectroscopy confirm that adduct 5 exists as a
      1:1 mixture of rotamers in solution as a result of the mutual repulsion between
      the cis-oriented pyridine and guanine bases. While 2 readily reacts with DNA
      nitrogen, its monofunctional adducts show no significant effect on the
      conformation of native DNA. Circular dichroism (CD) spectra recorded of platinum
      modified calf-thymus DNA suggest that the structural damage produced by complex 2
      does not mimic that produced by the clinical agent. Both the unusual reactivity
      and the inability to induce cisplatin-like DNA conformational changes are
      proposed to be responsible for the marginal biological activity of the new
      complexes.

PMID- 16087243
TI  - Efficient differentiation and integration of lineage-restricted neural precursors
      in the traumatically injured adult cat spinal cord.
AB  - Several recent studies have shown that highly undifferentiated neural stem cells
      (NSCs) grafted into the intact or injured adult spinal cord of animal either
      remain undifferentiated or show fate restriction to a astrocytic lineage. This
      indicates that functionally diverse roles expected of cellular replacement cannot
      be performed by the transplantation of highly immature precursors; rather, more
      differentiated or appropriate mixtures of more restricted neural precursors may
      be important in replacement strategies. In this study, we investigated the
      ability of lineage-restricted neural progenitors derived from adult mouse
      periventricular subependymal zone (SEZ) to integrate and differentiate into the
      chronically injured adult spinal cord. To this end, NSCs were grown as adherent
      cultures followed by expansion in non-adhesive dishes. This allowed us to grow
      NSCs as colonies of restricted neural precursors, illustrated by NCAM, nestin,
      Sox-2, A2B5, and GFAP immunostaining. The mixture of lineage-restricted
      precursors was directly implanted into the chronically injured spinal cord of
      immunosuppressed cats. The fate of the cells was traced with GFP fluorescence and
      immunocytochemistry for neural markers such as beta-III-tubulin, GFAP, and Ng2.
      After four weeks, transplanted cells survived, giving rise to neurons and in
      addition to cells with an astrocytic phenotype. We conclude that a mixture of
      more restricted neural precursors may be better suited than highly immature NSCs
      for neural replacement strategies after central nervous system (CNS) injuries.

PMID- 16087244
TI  - Phospho-CREB and other phospho-proteins: improved recovery from brain tissue.
AB  - During attempts to quantify levels of phosphorylated cAMP response element
      binding protein (CREB-P) in guinea pig brain stem auditory nuclei by Western
      blotting, we compared the decay of CREB-P levels when tissues were homogenized in
      traditional Lysis buffer containing detergents or in 50 mM Tris-HCl buffer
      containing 0.32 M sucrose. The decay of CREB-P levels was retarded considerably
      in the Tris-Sucrose medium as compared to the Lysis buffer. Similarly, the levels
      of two other phospho-proteins, extracellular regulated kinases (ERK1/2-P) and
      stress activated protein/Jun-N-terminal kinase (SAP/JNK-P), were better preserved
      by the Tris-Sucrose medium. These findings imply that the detergents typically
      present in the Lysis buffer may disrupt organelles and increase the exposure of
      soluble phospho-proteins to hydrolyzing enzymes. In contrast, such exposure was
      probably minimized in the Tris-Sucrose medium, which is thought to preserve
      organelle integrity.

PMID- 16087245
TI  - Downregulation of VLA-4 on T cells as a marker of long term treatment response to
      interferon beta-1a in MS.
AB  - We determined longitudinally the expression of a panel of adhesion molecules on T
      cells and soluble ICAM-1, VCAM-1 and tumor necrosis factor apoptosis inducing
      ligand (TRAIL) in serum during first year of the PRISMS Study with IFNbeta1a in
      MS. Clinical data and quantitative MRI data were available for 4 years. VLA-4 was
      down-regulated on T cells and VCAM-1 was up-regulated in serum during the first 3
      to 6 months of therapy in patients with favorable long-term treatment response
      (EDSS progression </=1.0 in 4 years). Short disease duration and low EDSS were
      clinical pre-treatment characteristics related to good long-term response to
      therapy.

PMID- 16087246
TI  - Functional expression of CCL6 by rat microglia: a possible role of CCL6 in cell
      cell communication.
AB  - There is growing evidence that chemokines play important roles in the immune
      surveillance of central nervous system (CNS). In the CNS, microglia are primary
      immune effector cells and secrete various chemokines in response to their
      microenvironment. Using the RT-PCR procedure and indirect immunofluorescence
      analysis, we found that CCL6 (known as C10/MRP-1 in mouse) was expressed in rat
      primary microglia without any stimulation, but not in primary astrocytes,
      although both cell types expressed CCR1 mRNA, which is a receptor for CCL6.
      Furthermore, immunohistochemical analysis demonstrated that microglia produced
      CCL6 protein in a normal brain, suggesting that microglia may be the primary
      source of CCL6 in a normal brain. Recombinant rat CCL6 mediated the migration of
      microglia and astrocytes in vitro. The CCL6-mediated cell migration was blocked
      by treating the cells with LY294002, a PI3-kinase inhibitor and Western blot
      analysis showed that the phosphorylation of Akt could be induced by treating
      microglia with a recombinant CCL6, suggesting that CCL6 functions by activating
      the PI3-kinase/Akt pathway. A proinflammatory cytokine, interferon-gamma enhanced
      the expression of both CCL6 mRNA and protein in microglia, while other
      proinflammatory cytokines, interleukin-6 and tumor necrosis factor-alpha and an
      anti-inflammatory cytokine, transforming growth factor-beta exerted no effect on
      CCL6 expression in microglia. These findings suggest that CCL6 may be a mediator
      released by microglia for cell-cell communication under physiological as well as
      pathological conditions of CNS.

PMID- 16087247
TI  - Increased levels of APRIL (a proliferation-inducing ligand) mRNA in multiple
      sclerosis.
AB  - B cells play an indispensable, yet indeterminate, role in the pathogenesis of
      multiple sclerosis (MS). We measured mRNA of APRIL-a promotor of B-cell survival
      in peripheral blood and quantified protein levels in plasma and cerebrospinal
      fluid in MS patients and controls. APRIL mRNA levels in monocytes and T cells
      were significantly higher in MS patients than in controls. Levels of soluble
      APRIL in plasma were higher in patients with chronic progressive MS than in
      patients with relapsing-remitting MS, albeit not significantly. MS may thus be
      associated with increased transcription in peripheral blood of factors promoting
      B-cell survival, including APRIL.

PMID- 16087248
TI  - Determining genetic stabilities of chimeric dengue vaccine candidates based on
      dengue 2 PDK-53 virus by sequencing and quantitative TaqMAMA.
AB  - The genetic stabilities of the three attenuation loci of the candidate dengue 2
      (D2) PDK-53 vaccine virus were evaluated for the PDK-53 virus and PDK-53-vectored
      chimeric D2/1, D2/3, and D2/4 viruses following 10 sequential passages in Vero
      cells. Sequencing revealed that the dominant NS1-53-Asp and the NS3-250-Val
      attenuation loci were extremely stable, whereas reversion occurred at the 5'NCR
      57-U locus in 10 of the 18 viral lineages tested. A more sensitive and
      quantitative assay, the TaqMan mismatch amplification mutation assay (TaqMAMA),
      was employed to more finely discriminate the level of reversion at the 5'NCR-57
      locus. This rapid genetic assay permitted detection of <or=1% reversion of 5'NCR
      57 U-to-C in viral populations. By TaqMAMA, various levels of reversion at 5'NCR
      57 were detected in all 18 of the PDK-53-based viral lineages tested at Vero
      passage 10, but only 3 lineages had reversion levels>80% in the viral population.
      Chimeric viruses based on the PDK-53-V (all three mutations present) genetic
      background were more stable than those developed in the PDK-53-E (5'NCR and NS1
      mutations present) background. The TaqMAMA can be applied in quality control
      analyses to ensure that attenuated vaccine seeds contain undetectable or minimal
      levels of reversion at a given attenuation locus.

PMID- 16087249
TI  - PENS, the new joint Programme for European Neuroscience Schools: FENS and IBRO
      turn past into future.

PMID- 16087250
TI  - In vitro and in vivo influenza virus-inhibitory effects of viramidine.
AB  - Viramidine, the 3-carboxamidine derivative of ribavirin, was effective against a
      spectrum of influenza A (H1N1, H3N2 and H5N1) and B viruses in vitro, with the
      50% effective concentration (EC50) ranging from 2 to 32 microg/ml. The mean 50%
      cytotoxic concentration (CC50) in the MDCK cells used in these experiments was
      760 microg/ml. Ribavirin, run in parallel, had a similar antiviral spectrum, with
      EC50 values ranging from 0.6 to 5.5 microg/ml; the mean CC50 for ribavirin was
      560 microg/ml. Oral gavage administrations of viramidine or ribavirin to mice
      infected with influenza A/NWS/33 (H1N1), A/Victoria/3/75 (H3N2), B/Hong Kong/5/72
      or B/Sichuan/379/99 viruses were highly effective in preventing death, lessening
      decline in arterial oxygen saturation, inhibition of lung consolidation and
      reducing lung virus titers. The minimum effective dose of viramidine in these
      studies ranged from 15 to 31 mg/kg/day, depending upon the virus infection, when
      administered twice daily for 5 days beginning 4 h pre-virus exposure. The LD50 of
      the compound was 610 mg/kg/day. Ribavirin's minimum effective dose varied between
      18 and 37.5 mg/kg/day with the LD50 determined to be 220 mg/kg/day. Viramidine's
      efficacy was also seen against an influenza A/NWS/33 (H1N1) virus infection in
      mice, when the compound was administered in the drinking water, the minimum
      effective dose being 100 mg/kg/day. Delay of the initiation of either viramidine
      or ribavirin therapy, using the approximate 1/3 LD50 dose of each, was protective
      as late as 48 h after exposure to the A/NWS/33 virus. While both compounds appear
      to have similar efficacy against influenza virus infections, when one considers
      the lesser toxicity, viramidine may warrant further evaluation as a possible
      therapy for influenza.

PMID- 16087251
TI  - A proposal of decision tree to screen putative antidepressants using forced swim
      and tail suspension tests.
AB  - Interstrain mice variability in response to antidepressant drugs has been
      reported in the most commonly utilized behavioural animal models of depression:
      the tail suspension test (TST) and the forced swimming test (FST). The behaviour
      of mice was examined in both tests for screening various antidepressants with
      different biochemical mechanism of action. Previous studies have revealed that
      drug sensitivity depends on the strain and test used. Swiss mice is the most
      sensitive strain to detect serotonin and/or noradrenaline antidepressants whereas
      C57BL/6J was the only strain sensitive to bupropion (dopaminergic agent) using
      the FST. In the TST, all antidepressants studied decreased the immobility time in
      Swiss and C57BL/6J strains. Detection of an antidepressant-like activity could be
      performed using only one test (TST with Swiss mice or FST with Swiss and C57Bl/6
      Rj mice), but both tests are necessary to conclude on the mechanism of action.

PMID- 16087252
TI  - Laboratory and field assessment of uranium trophic transfer efficiency in the
      crayfish Orconectes limosus fed the bivalve C. fluminea.
AB  - At present, ecotoxicological information regarding the impact of natural uranium
      (U) on freshwater ecosystems via the trophic contamination route is scarce. We
      generated an experimental trophic food chain involving the prey species,
      Corbicula fluminea, and a predator, Orconectes limosus, for a 10-day and a 30-day
      feeding periods (food ration: one whole soft body/day/crayfish). We studied the
      efficiency of U trophic transfer and the distribution of U in the predator.
      During the test, we varied the quantity of dietary U (from beforehand
      contaminated bivalves at concentrations ranging from 0.9+/-0.1 to 20.2+/-9
      microg/g fw provided to each crayfish over the 10 days) applying a daily feeding
      rate equal to 3.9+/-0.8% fw. The efficiency of U trophic transfer from clams to
      crayfish varied between 1 and 13% depending on the prey exposure modalities.
      Accumulation of U was observed in the digestive gland but also in gills, in the
      muscle, and in the molt of the crayfish after trophic exposure treatments. Under
      high-level exposure conditions, the digestive gland was the main target-organ,
      however a significant accumulation was also observed in the stomach. With regard
      to low levels of trophic exposure, accumulation of U in gills, in the stomach,
      and in the digestive gland was of the same order of magnitude. Longer exposure
      period which incorporated a crayfish molt, resulted in a decrease of trophic
      transfer ratio and a modified U tissue distribution.

PMID- 16087253
TI  - Antioxidant efficiency in early life stages of the Antarctic silverfish,
      Pleuragramma antarcticum: responsiveness to pro-oxidant conditions of platelet
      ice and chemical exposure.
AB  - The Antarctic silverfish Pleuragramma antarcticum is a key organism in the
      ecology of Southern Ocean. Eggs with fully developed yolk-sac embryos and newly
      hatched larvae have been recently observed to occur in the platelet ice
      accumulating below the sea-ice layer. This environment has strong pro-oxidant
      characteristics at the beginning of austral spring, when the rapid growth of
      algal ice communities, the massive release of nutrients and the photoactivation
      of dissolved organic carbon and nitrates, all represent important sources for
      oxyradical formation. Such processes are concentrated in a short period of a few
      weeks which overlaps with the final development of P. antarcticum in platelet
      ice. The aim of this work was to characterize the antioxidant system in embryos
      of P. antarcticum and the responsiveness toward the natural increase of pro
      oxidant conditions in early spring. Considering the lack of ecotoxicological data
      on this species and its pivotal importance in the ecosystem of Southern Ocean,
      the sensitivity of its early life stages was also evaluated after laboratory
      exposures to environmentally relevant doses of benzo(a)pyrene, as a model
      chemical potentially released from anthropogenic activities. Obtained results
      revealed a marked temporal increase of antioxidants in embryos of P. antarcticum
      as adaptive counteracting responses to oxidative conditions of platelet ice.
      Particularly prompt responses were observed for glutathione metabolism which,
      however, did not prevent formation of increasing levels of lipid peroxidation
      products; from the analysis of total oxyradical scavenging capacity (TOSC), the
      overall efficiency to neutralize peroxyl radicals remained almost constant while
      slightly lower TOSC values were obtained toward hydroxyl radicals at the end of
      sampling period. Laboratory exposures to 0.5-5 microg/l BaP caused a significant
      accumulation of this PAH but no significant effects on the activity of cytochrome
      P450. Antioxidants of exposed embryos showed less marked variations than embryos
      in field conditions suggesting that the elevated pro-oxidant challenge, to which
      these organisms are naturally adapted, might be responsible for the moderate
      responsiveness to pro-oxidant chemicals.

PMID- 16087254
TI  - Anti-inflammatory therapies in atrial fibrillation.

PMID- 16087255
TI  - Reduced plasma levels of NGF and BDNF in patients with acute coronary syndromes.

PMID- 16087256
TI  - Inflammation and anti-inflammatory interventions in atrial fibrillation.

PMID- 16087257
TI  - Hand-held echocardiography: its use and usefulness.
AB  - In recent years, several echocardiographic hand-held devices have been developed
      and are now available for a growing number of cardiologists. After the first
      clinical use 25 years ago, hand-held echocardiography (HHE) is now earning
      important commercial positions. Their transportability permits echo performance
      out the echo-labs and offers the possibility to make diagnosis in intensive care
      unit, emergency room, outpatient clinic, at the bedside, and even in ambulance.
      Experiences in the clinical setting have demonstrated the ability of HHE to
      detect multiple diseases including abdominal aortic aneurysms, left ventricular
      hypertrophy, regional wall motion abnormalities, pericardial and pleural
      effusions. At the present time, four varieties of HHE have to be recognized: the
      first includes high-cost, miniaturized machines, similar to the most advanced
      instrumentations, provided by new tools and imaging transfer systems; a second
      intermediate, middle-cost variety encompasses devices corresponding to standard
      echocardiography, but not miniaturized; according to the definition of the
      American Society of Echocardiography, a third and a fourth category comprise
      machines of weight lower than 2.7 kg, battery supplied and appropriately defined
      as "portable cardioschopes", which can be utilized as a technical refinement of
      physical examination. The use of HHE opens main controversy concerning their
      diagnostic accuracy, the opportunity to establish in which clinical settings they
      should be used and the identification of both potential users and required
      competence level. Preliminary experiences show the possibility to improve and
      anticipate diagnosis of several cardiovascular diseases but also the need to plan
      specific ultrasound training to avoid incorrect use of HHE.

PMID- 16087258
TI  - Tissue velocity imaging during dobutamine stimulation for assessment of
      myocardial viability: segmental analysis in patients after myocardial infarction.
AB  - BACKGROUND: Dobutamine stress echocardiography (DSE) is an established method for
      the detection of viable myocardium, but evaluation of this method is subjective.
      Tissue velocity Imaging (TVI) allows quantitative analysis of regional myocardial
      wall motion by assessment of systolic myocardial velocities. The aim of this
      study was to evaluate the diagnostic value of DSE and TVI for detection of viable
      myocardium. METHODS: In 56 patients (58+/-12 years) with previous myocardial
      infarction (130+/-42 days, mean ejection fraction 42+/-15%) low-dose DSE was
      combined with analysis of peak systolic myocardial velocities (Vpeak) by TVI for
      assessment of myocardial viability. As reference served a follow-up
      echocardiography after successful revascularization (mean 91+/-3 days). RESULTS:
      Of a total of 896 segments 200 showed abnormal wall motion (31 mildly
      hypokinetic, 50 severely hypokinetic, 115 akinetic, 4 dyskinetic). In 125 of
      these 200 segments regional improvement of regional wall motion was observed
      (62.5% viable). An increase of Vpeak>1 cm/s during dobutamine stimulation allowed
      the identification of viable myocardium with a sensitivity of 82% and a
      specificity 82% (DSE: 77% and 80%). By receiver operating characteristic (ROC)
      curve analysis, a cut-off value of 1.0 cm/s was the best parameter to differ
      viable from nonviable myocardium (area under the curve 0.85; p<0.01; 95% CI 0.79
      to 0.90). Improvement of global ejection fraction after revascularization (47+/
      13%, p=0.11) corresponded with three TVI viable segments with a sensitivity of
      92% and a specificity of 89% (p=0.012). CONCLUSIONS: TVI allows the
      identification of viable myocardium during dobutamine stimulation and enables a
      quantitative interpretation of DSE.

PMID- 16087259
TI  - Correlation between ABO blood groups, major risk factors, and coronary artery
      disease.
AB  - To investigate a possible association of ABO blood groups with coronary artery
      disease in well-documented patients, we designed a cross-sectional study of 2026
      patients, known case of coronary artery disease in angiography, who underwent
      coronary artery bypass graft at Tehran Heart Center, with regard to coronary
      artery disease major risk factors as well as ABO blood groups. Analysis did not
      show any significant difference between the frequency of ABO blood groups in
      coronary artery disease patients compared to the Iranian general population. In
      addition, frequency of cardiac risk factors was similar in coronary artery
      disease patients with different blood groups. Therefore, these finding suggest
      that there is no correlation between various ABO blood groups and development of
      coronary artery disease. Moreover, the prevalence of major risk factors was equal
      in patients with different blood groups, and blood groups had no impact on
      development of premature coronary artery disease in individual subjects.

PMID- 16087260
TI  - Extraordinary claims require extraordinary evidence.

PMID- 16087261
TI  - Site-directed gene replacement of the phytopathogen Xanthomonas axonopodis pv.
      citri.
AB  - In this work we defined experimental conditions for site-directed gene
      replacement of the Xanthomonas axonopodis pv. citri (Xac), an economically
      relevant pathogen of citrus plants. The procedure involved, first, optimizing the
      electrotransformation conditions of the Xac 306 strain and, second, constructing
      non-replicative suicide vectors carrying knockout copies of the target gene.
      Using specific experimental conditions, transformation efficiencies of Xac were
      at least 100 fold higher than those achieved with electroporation protocols
      previously designed for X. campestris transformation. Successful gene replacement
      events were achieved with a suicide vector derived from R6K plasmid (pWR-SS) but
      not with those with ColE1 replication origin. We have chosen the oppA as a target
      gene, encoding the binding component (OppA) of the major oligopeptide uptake
      system found in the genome of the Xac 306 strain, although not in X. campestris
      pv. campestris (Xcc). Defining the experimental conditions, which allow for the
      specific mutagenesis of the Xac 306 strain, represents a step in the
      understanding of both genetics and physiology of this economically important
      bacterial species.

PMID- 16087262
TI  - The relationship between initial errorless learning conditions and subsequent
      performance.
AB  - This experiment explores a suggestion by [Maxwell, J.P., Masters, R.S.W., Kerr,
      E., Weedon, E. (2001). The implicit benefit of learning without errors. Quarterly
      Journal of Experimental Psychology A 54, 1049-1068] that an initial bout of
      implicit motor learning confers beneficial performance characteristics, such as
      robustness under secondary task loading, despite subsequent explicit learning.
      Participants acquired a complex motor skill (golf putting) over 400 trials. The
      environment was constrained early in learning to minimize performance error. It
      was predicted that in the absence of explicit instruction, reducing error would
      prevent hypothesis testing strategies and the concomitant accrual of declarative
      (explicit) knowledge, thereby reducing dependence on working memory resources.
      The effect of an additional cognitive task on putting performance was used to
      assess reliance on working memory. Putting performance of participants in the
      Implicit-Explicit condition was unaffected by the additional cognitive load,
      whereas the performance of Explicit participants deteriorated. The relationship
      between error correction and episodic verbal reports suggested that the explicit
      group were involved in more hypothesis testing behaviours than the Implicit
      Explicit group early in learning. It was concluded that a constrained,
      uninstructed, environment early in learning, results in procedurally based motor
      output unencumbered by disadvantages associated with working memory control.

PMID- 16087263
TI  - Implicit perceptual training: how, when, and why?
AB  - The perceptual skills underlying anticipatory movement in sport have been the
      focus of much research over the past 20 years. Methods for training such skills
      have tended to emphasise explicit specification of discriminative cues and the
      rules linking changes in the perceptual field with required responses. Recently,
      researchers have begun to examine less prescriptive methods of training. In the
      present paper, we examine conceptual, methodological, and practical issues
      associated with whether such skills can or indeed should be trained implicitly.
      The implications of two ways of conceptualising the explicit-implicit distinction
      for the methods used to promote implicit learning and the tests used to assess
      the nature of learning are considered. Finally, potential advantages of
      implicitly learned skills relating to task complexity and robustness under stress
      are discussed.

PMID- 16087264
TI  - Effects of correct and transformed visual feedback on rhythmic visuo-motor
      tracking: tracking performance and visual search behavior.
AB  - The effects of correct and transformed visual feedback on rhythmic unimanual
      visuo-motor tracking were examined, focusing on tracking performance (accuracy
      and stability) and visual search behavior. Twelve participants (reduced to 9 in
      the analyses) manually tracked an oscillating visual target signal in phase (by
      moving the hand in the same direction as the target signal) and in antiphase (by
      moving the hand in the opposite direction), while the frequency of the target
      signal was gradually increased to probe pattern stability. Besides a control
      condition without feedback, correct feedback (representing the actual hand
      movement) or mirrored feedback (representing the hand movement transformed by 180
      degrees) were provided during tracking, resulting in either in-phase or antiphase
      visual motion of the target and feedback signal, depending on the tracking mode
      performed. The quality (accuracy and stability) of in-phase tracking was hardly
      affected by the two forms of feedback, whereas antiphase tracking clearly
      benefited from mirrored feedback but not from correct feedback. This finding
      extends previous results indicating that the performance of visuo-motor
      coordination tasks is aided by visual feedback manipulations resulting in
      coherently grouped (i.e., in-phase) visual motion structures. Further insights
      into visuo-motor tracking with and without feedback were garnered from the visual
      search patterns accompanying task performance. Smooth pursuit eye movements only
      occurred at lower oscillation frequencies and prevailed during in-phase tracking
      and when target and feedback signal moved in phase. At higher frequencies, point
      of-gaze was fixated at a location that depended on the feedback provided and the
      resulting visual motion structures. During in-phase tracking the mirrored
      feedback was ignored, which explains why performance was not affected in this
      condition. Point-of-gaze fixations at one of the end-points were accompanied by
      reduced motor variability at this location, reflecting a form of visuo-motor
      anchoring that may support the pick up of discrete information as well as the
      control of hand movements to a desired location.

PMID- 16087265
TI  - Carbon dioxide stimulates the production of amylovorin L by Lactobacillus
      amylovorus DCE 471, while enhanced aeration causes biphasic kinetics of growth
      and bacteriocin production.
AB  - The effects of both oxygen and carbon dioxide on growth of and product formation
      by Lactobacillus amylovorus DCE 471, a promising new sourdough starter culture,
      were assessed through controlled, in vitro fermentation experiments, using a
      temperature of 37 degrees C and a constant pH of 5.4. It was seen that aeration
      affected both cell growth and amylovorin L production. At aeration rates of 1 l
      min(-1) and more, the bacterial population was subjected to oxidative stress as
      reflected by biphasic growth patterns. During the first growth phase, the maximum
      specific growth rate increased with increasing aeration rates stabilizing at the
      highest oxygen concentrations. The maximum obtainable cell yields decreased.
      During the second growth phase, the amylovorin L production was stimulated at the
      highest aeration. However, amylovorin titers were never higher in the presence of
      oxygen compared with the anaerobic fermentations. Carbon dioxide did not
      influence cell growth of L. amylovorus DCE 471. The maximum specific growth rate
      and the biomass concentrations were merely affected. On the other hand, the
      maximum soluble bacteriocin titers coincided with the highest carbon dioxide flow
      rates. These results indicate that mild aeration of type II sourdoughs might
      enhance both cell yield and amylovorin L production by L. amylovorus DCE 471,
      thereby contributing to the competitiveness of the strain. Growth in an ecosystem
      together with yeasts producing carbon dioxide might exert a positive effect on
      the production of amylovorin L as well.

PMID- 16087266
TI  - Immobilization and biocatalysis of chlorophyllase in selected organic solvent
      systems.
AB  - Chlorophyllase extract from Phaeodactylum tricornutum was immobilized by physical
      adsorption on DEAE-cellulose and silica gel as well as by covalent binding on
      Eupergit C, Eupergit C250L, Eupergit C/ethylenediamine (EDA) and Eupergit
      C250L/EDA. Although the highest immobilization yield (83-93%) and efficiency (51
      53%) were obtained when chlorophyllase extract was immobilized on DEAE-cellulose
      and silica gel, there was no improvement in the thermal stability of
      chlorophyllase as compared to that of the free one. The immobilization of
      chlorophyllase extract on Eupergit C250L/EDA resulted by a high recovery of
      enzymatic activity, with an immobilization efficiency of 44%, and promoted a
      higher stabilization of chlorophyllase (four times) in the aqueous/miscible
      organic solvent medium. On the other hand, the inhibitory effect of refined
      bleached deodorized (RBD) canola oil was reduced by immobilization of
      chlorophyllase extract onto silica gel as compared to those obtained with other
      enzyme preparations. However, the re-cycled chlorophyllase extract immobilized on
      Eupergit C250L/EDA retained more than 75% of its initial enzyme activity after 6
      cycles, whereas that immobilized on silica gel was completely inactivated. The
      highest catalytic efficiency, for both free and immobilized chlorophyllase on
      Eupergit C250L/EDA, was obtained in the ternary micellar system as compared to
      the aqueous/miscible organic solvent and biphasic media.

PMID- 16087267
TI  - Skin permeation and stability studies of 5-aminolevulinic acid in a new gel and
      patch preparation.
AB  - A new cubic gel as well as a patch system containing additional carrageenan as
      matrix were used as vehicles for 5-aminolevulinic acid (5-ALA). Standard
      diffusion experiments of 5-ALA using Franz-type diffusion cells and porcine skin
      were performed. Drug stability was monitored by analysing the 5-ALA content in
      the formulations. The analysis of 5-ALA as non-fluorescent probe was performed
      after chemical reaction leading to a fluorescent derivative. The 5-ALA permeation
      through porcine skin after 48 h was the highest from the patch formulation with
      80.3% and the second highest from the cubic gel with 66.4%, however only about
      40% of 5-ALA were chemical stable after 14 days storage in the patch formulation,
      whereas no degradation of 5-ALA was measured in the cubic gel over 90 days of
      observation.

PMID- 16087268
TI  - Transcription of plasmid DNA: influence of plasmid DNA/polyethylenimine complex
      formation.
AB  - Polyethylenimine (PEI) is one of the most potent non-viral vectors. We have
      developed a lactosylated PEI (Lac-PEI) to enhance cell-specific transfection and
      have shown that Lac-PEI is more efficient than unsubstituted PEI for gene
      transfer into immortalized cystic fibrosis airway epithelial SigmaCFTE29o-cells.
      As both intact PEI/plasmid and Lac-PEI/plasmid complexes are found in the cell
      nucleus, we have investigated the transcription efficiency of the plasmid
      complexed with PEI or Lac-PEI, according to the polymer nitrogen/DNA phosphate
      (N/P) ratio (from 0 to 20). The initiation of transgene transcription was
      analyzed in an acellular nuclease S1 transcription assay. For both PEI and Lac
      PEI complexes, transcription efficiency varied with the N/P ratio of the
      complexes. Transcription inhibition was observed when plasmid DNA was either
      loosely (N/P<5) or tightly condensed (N/P>15). For an N/P ratio of 5 and up to
      15, transcription of the complexed plasmid was as efficient as that of the free
      plasmid. Similar results were observed when gene expression was studied after
      nuclear microinjection of the complexes into SigmaCFTE29o-cells. Our study shows
      that condensation of DNA influences the accessibility of the plasmid to the
      transcription machinery. Interestingly, the charge ratios that allow the most
      efficient transcription are those usually known to be the most efficient for gene
      transfer in vitro and in vivo.

PMID- 16087269
TI  - Professional accountability for diabetes care in Taiwan.
AB  - This study examined the performance of diabetes care measures in Taiwan and
      evaluated the influencing factors for professional accountability. We analyzed
      the year 2001 claims data from National Health Insurance (NHI) program in Taipei
      Branch. Professional accountability for diabetes care was measured by the
      adherence for laboratory monitor, either from patient- or hospital-viewpoint.
      Identifying the major care unit for each patient, a multiple logistic regression
      model was used to further assess the mixed effects of patient and hospital
      characteristics. The percentage of patients ever received measures in the year
      for plasma glucose, A(1C), urinalysis, renal function test, lipid profile, liver
      function test, and eye ground was 76.3, 42.7, 40.2, 59.7, 59.2, 53.2, and 16.8%
      respectively. About 19.2% patients never received any one of the measures.
      Patients with hypoglycemic, anti-hypertensive or anti-hyperlipidemic agents,
      hospitalization, emergency service visit and frequent visits were more likely to
      receive exams. Hospitals with different levels, ownerships, locales or
      qualifications as diabetes care institutions presented different accountability
      for diabetes care measures. After regression, counts of visits and levels of
      hospitals had persistently effects on all the measures. Our analysis revealed sub
      optimal diabetes care in Taiwan and concluded the importance of enhancing care
      quality from primary settings.

PMID- 16087270
TI  - Activation of dendritic cells by local ablation of hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Local ablation methods are an effective treatment for
      hepatocellular carcinoma (HCC). The rate of recurrence or development of intra
      hepatic metastases may be lowered by antitumoral immune responses. Since HCCs are
      in general only weakly immunogenic, cell injury induced by local tumor ablation
      (PEI/RFTA) may increase HCC immunogenicity and may release endogenous adjuvants
      that activate dendritic cells (DC). The aim of the study, therefore, was the
      analysis whether PEI or RFTA induced injury results in an adjuvant effect for
      immune responses to HCCs. METHODS: Eight HCC patients were treated with PEI or
      RFTA and serially analyzed for 4 weeks. Plasmocytoid (PDC) and myeloid dendritic
      cells (MDC) were analyzed directly ex vivo and in vitro using FACS and
      proliferation assays. RESULTS: HCC ablation induced a functional transient
      activation of MDC but not of PDC associated with increased serum levels of TNF
      alpha and IL-1beta. CONCLUSIONS: These findings suggest that the combination of
      PEI or RFTA and active antigen specific immunotherapeutic approaches using DCs is
      a promising approach for the induction of sustained antitumoral immune responses
      aiming at the reduction of tumor recurrence and metastases in HCC patients.

PMID- 16087271
TI  - Gender-dependent hepatic alterations in H-ras12V transgenic mice.
AB  - BACKGROUND/AIMS: Although it has been proposed that Ras and related signal
      pathways play important roles in hepatocarcinogenesis, appropriate in vivo models
      are lacking. METHODS: Two hepatocellular carcinoma lines were established using
      pronuclear microinjection techniques to create an insertion of the H-ras12V
      transgene under the control of the albumin enhancer/promoter. The resulting
      phenotypes and related molecular events were then examined. RESULTS: Male (but
      not female) transgenic mice older than 2 months showed hepatic alterations with a
      high degree of reproducibility, as compared to the wild-type mice. The liver/body
      weight ratios were lower for the females than for the males. The transgene
      carrying line 28 was investigated extensively with respect to molecular
      differences between the genders. Male hepatocytes showed higher Ras activity and
      higher reactive oxygen species (ROS) levels than female hepatocytes. The female
      hepatocytes showed higher expression levels of p53 and p21Waf1/Cip1, enhanced
      cytochrome c release, which correlated with cell cycle arrest, and higher levels
      of hypodiploid cell formation, as compared to the male hepatocytes. CONCLUSIONS:
      The gender-related differences in molecular responses to activated Ras may have
      implications for the prevalence of hepatic alterations in males. Our transgenic
      mice represent a potentially valuable animal model for future investigations.

PMID- 16087272
TI  - Pifithrin-alpha induced p53 inhibition does not affect liver regeneration after
      partial hepatectomy in mice.
AB  - BACKGROUND/AIMS: Beside its well-known function as tumour suppressor gene, p53 is
      supposed to positively regulate cell division and cell differentiation. Because
      hepatocyte proliferation has been reported to be reduced by blockade of p53
      function in vitro, we examined in the present study the impact of p53 inhibition
      on hepatocyte proliferation in vivo. METHODS: Mice treated with either pifithrin
      alpha (PFT), a p53-inactivating agent, or the equivalent volume of vehicle, were
      subjected to 70% hepatectomy. In addition to assessment of liver mass restitution
      we examined p53 and p21 protein expression as well as PCNA expression and BrdU
      incorporation by using Western blot and immunohistochemical techniques. Extent of
      apoptosis was assessed by TUNEL assay. RESULTS: PFT lowered nuclear but not
      cytoplasmic p53, and did not inhibit protein expression of regeneration
      associated p21. PCNA protein expression as well as PCNA and BrdU
      immunohistochemistry did not differ between regenerating livers of either PFT- or
      vehicle-treated animals. Moreover, TUNEL analysis of regenerated liver tissue
      revealed comparable numbers of apoptotic cells in both groups. CONCLUSIONS:
      Pharmacological inhibition of p53 did not impair liver regeneration in mice,
      implying that p53 is functionally redundant in that p53-independent pathways
      compensate for the blockade of p53 and sufficiently support the process of
      hepatocyte replication in liver regeneration.

PMID- 16087273
TI  - Hepatitis B virus genotypes and extrahepatic manifestations.
AB  - BACKGROUND/AIMS: This study aimed at correlating the presence of extrahepatic
      manifestations with hepatitis B virus (HBV) genotypes in patients with chronic
      HBV infection. METHODS: This was a national (France), multicenter, retrospective,
      cross-sectional study. HBV genotypes were determined in 190 patients HBsAg
      positive for at least 6 months and documented before any treatment. RESULTS:
      Patients were aged 42+/-15 years and mainly male (77%). Alcohol intake was high
      in 6% of them, ALT elevated in 73%; 27% were cirrhotic. All HBV genotypes were
      found, mainly A (24%), D (29%), C (11%), and E (10%). Thirty (16%) patients had
      clinical extrahepatic manifestations, mainly sensory-motor deficiency, sicca
      syndrome, myalgia, glomerulonephritis, and arthralgia-arthritis. Their presence
      was not related to any epidemiologic, viral (including genotypes) or hepatic
      factor, but to a higher platelet count (P=0.004). Twenty-nine (15%) patients had
      biological extrahepatic manifestations, mainly anti-smooth muscle, antinuclear,
      and anti-nucleosome antibodies. Their presence was related only to anti-HBe
      antibodies positivity (P=0.007) or elevated platelet count (P=0.003). Carrying
      precore mutant HBV increased by 2.8 folds the risk to have at least one
      extrahepatic biological manifestation. CONCLUSIONS: No relationships between HBV
      genotypes and the presence of extrahepatic manifestations were evidenced in
      patients with chronic HBV infection.

PMID- 16087274
TI  - A novel antimicrobial peptide from salivary glands of the hard tick, Ixodes
      sinensis.
AB  - A novel antimicrobial peptide named as ixosin was isolated from the salivary
      glands of the hard tick, Ixodes sinensis, by gel filtration, ion exchange
      chromatography and reverse-phase high-performance liquid chromatography (RP
      HPLC). Its amino acid sequence was determined as GLHKVMREVLGYERNSYKKFFLR by Edman
      degradation and its molecular weight was 2870.5 analyzed by fast atom bombardment
      (FAB) mass spectrometry. This is the first antimicrobial peptide from ticks that
      lacks cysteine in its primary structure. The cDNA encoding ixosin was cloned by
      cDNA library screening. The predicted protein from the cDNA sequence composed of
      79 amino acids including mature ixosin. Purified ixosin exerted its antimicrobial
      activities against bacteria and fungi. No similarity was found by BLAST search to
      any database entries and, thus, our findings describe a novel antimicrobial
      peptide.

PMID- 16087276
TI  - A one-enzyme strategy to release an antimicrobial peptide from the LFampin-domain
      of bovine lactoferrin.
AB  - Antimicrobial peptides have been found throughout living nature, yet
      antimicrobial sequences may still lie hidden within a wide variety of proteins. A
      rational strategy was developed to select interesting domains, based on the
      presumed common features of antimicrobial peptides, and to release these from
      accessible and safe proteins. In silico proteolysis simulations of bovine
      lactoferrin (bLF) with selected endoproteinases predicted the liberation of
      peptides that encompasses a cationic amphipathic alpha-helix. Three predicted
      peptides were synthesized and tested for their biological activity, demonstrating
      that one single enzyme was sufficient to obtain an antimicrobial peptide. The
      proof of principle demonstrated that a 32-mer fragment isolated from the
      endoproteinase AspN digestion of bLF possessed strong antimicrobial activity.
      Moreover, desalted crude digest had improved activity over native bLF. Hence,
      selective digestion of bLF increases its antimicrobial activity by release of
      antimicrobial stretches.

PMID- 16087275
TI  - Enzymatic degradation studies of endomorphin-2 and its analogs containing N
      methylated amino acids.
AB  - In this paper, we describe the synthesis of novel endomorphin-2 analogs,
      containing N-methylated amino acids, consecutively in each position. The receptor
      binding profile of the new analogs and their stability against enzymatic cleavage
      by commercially available peptidases, carboxypeptidase Y and aminopeptidase M,
      and a rat brain homogenate are reported. The best analog of this series,
      [Sar2]endomorphin-2, was almost equipotent with the parent peptide in the mu
      receptor-binding assay and was also highly resistant to enzymatic degradation.
      This analog may be a suitable candidate for the in vivo antinociceptive studies.

PMID- 16087277
TI  - Cyclosporine a induces growth arrest or programmed cell death of human glioma
      cells.
AB  - Human malignant gliomas are highly resistant to current therapeutic approaches.
      We previously demonstrated that cyclosporine A (CsA) induces an apoptotic cell
      death in rat C6 glioma cells. In the present study, we found the induction of
      growth arrest or cell death of human malignant glioma cells exposed to CsA. In
      studied glioma cells, an accumulation of p21Cip1/Waf1 protein, a cell cycle
      inhibitor, was observed following CsA treatment, even in the absence of
      functional p53 tumour suppressor. CsA induced a senescence-associated growth
      arrest, in U87-MG glioma cells with functional p53, while in U373 and T98G glioma
      cells with mutated p53, CsA treatment triggered cell death associated with
      alterations of cell morphology, cytoplasm vacuolation, and condensation of
      chromatin. In T98G cells this effect was completely abolished by simultaneous
      treatment with an inhibitor of protein synthesis, cycloheximide (CHX). Moreover,
      CsA-induced cell death was accompanied by activation of executory caspases
      followed by PARP cleavage. CsA treatment did not elevate fasL expression and had
      no effect on mitochondrial membrane potential. We conclude that CsA triggers
      either growth arrest or non-apoptotic, programmed cell death in human malignant
      glioma cells. Moreover, CsA employs mechanisms different to those in the action
      of radio- and chemotherapeutics, and operating even in cells resistant to
      conventional treatments. Thus, CsA or related drugs may be an effective novel
      strategy to treat drug-resistant gliomas or complement apoptosis-based therapies.

PMID- 16087278
TI  - Work experience mitigated age-related differences in balance and mobility during
      surface accommodation.
AB  - BACKGROUND: Locomotor behavior at the roofing worksite is challenged by factors
      such as sloped surfaces, wind gusts and handling loads. Chronic exposure to this
      environment may result in enhanced locomotor strategies that are resistant to
      aging effects. The purpose of this study was to determine if roofers demonstrated
      enhanced locomotor strategies and if the strategies were maintained with age.
      METHODS: The gait of ten younger roofers (mean age 27.2 years), eight older
      roofers (55.4 years), ten younger controls (25.4 years) and nine older controls
      (57.6 years) was examined during level gait and stepping up onto a wooden surface
      (0.15m high). Subjects either carried no load, an empty box or the same box
      loaded to the equivalent of 5% body mass. FINDINGS: Work by age interactions were
      observed for toe clearance, step width, net angular momentum of the head, arms
      and trunk segment and gait speed (P<0.0001). Younger roofers demonstrated the
      greatest toe clearance; older roofers had a smaller lead clearance but decreased
      variability. Older control groups had the greatest risk of tripping due to low
      lead toe clearance and high variability, and were least likely to recover if they
      did trip due to faster gait speed and increased net angular momentum. Work
      experience resulted in enhanced changes in lead toe clearance and mitigated age
      related changes in step width and net angular momentum. INTERPRETATION:
      Challenging environments show promise for maintaining balance skills in older
      adults; however care should be taken when introducing inexperienced older adults
      to a challenging environment.

PMID- 16087279
TI  - Use of dolomite phosphate rock (DPR) fertilizers to reduce phosphorus leaching
      from sandy soil.
AB  - There is increasing concern over P leaching from sandy soils applied with water
      soluble P fertilizers. Laboratory column leaching experiments were conducted to
      evaluate P leaching from a typical acidic sandy soil in Florida amended with DPR
      fertilizers developed from dolomite phosphate rock (DPR) and N-Viro soil. Ten
      leaching events were carried out at an interval of 7 days, with a total leaching
      volume of 1,183 mm equivalent to the mean annual rainfall of this region during
      the period of 2001-2003. Leachates were collected and analyzed for total P and
      inorganic P. Phosphorus in the leachate was dominantly reactive, accounting for
      67.7-99.9% of total P leached. Phosphorus leaching loss mainly occurred in the
      first three leaching events, accounting for 62.0-98.8% of the total P leached
      over the whole period. The percentage of P leached (in the total P added) from
      the soil amended with water-soluble P fertilizer was higher than those receiving
      the DPR fertilizers. The former was up to 96.6%, whereas the latter ranged from
      0.3% to 3.8%. These results indicate that the use of N-Viro-based DPR fertilizers
      can reduce P leaching from sandy soils.

PMID- 16087280
TI  - Modeling the dynamic changes in concentrations of gamma-hexachlorocyclohexane
      (gamma-HCH) in Tianjin region from 1953 to 2020.
AB  - A level IV fugacity model was used to simulate the dynamic changes of gamma
      hexachlorocyclohexane (gamma-HCH) concentrations in environmental media in
      Tianjin, China. A similar model (level III) was previously used and validated
      under steady state conditions; this paper explores its dynamic behavior.
      Application of the level IV fugacity model has been validated using independently
      observed gamma-HCH concentrations in various media during the early 1980s and
      during 2001. Sensitivity analysis was conducted using coefficient-of-variation
      normalized sensitivity coefficients. The model was also subject to uncertainty
      analysis using Monte Carlo simulation. It was found that concentrations of gamma
      HCH reached within 95% of their steady-state levels in all media after less than
      15 years. Around one order-of-magnitude decreases in gamma-HCH concentrations in
      various media occurred between 1993 and 2001. We project that gamma-HCH
      concentrations will decrease another 1.7-1.9 orders of magnitude to reach 1.1
      (0.9-1.2) x 10(-14), 2.7 (2.5-3.0) x 10(-10), 1.2 (1.1-1.3) x 10(-7), and 6.1
      (5.4-6.8) x 10(-8) mol/m(3), in air, water, soil, and sediment, respectively, by
      2020. The sensitivities and true uncertainty of the model are discussed.

PMID- 16087281
TI  - The influence of salinity on metal uptake and effects in the midge Chironomus
      maddeni.
AB  - The influence of different porewater salinities (up to 12 g/L) on the toxicity
      and bioaccumulation of copper, zinc and lead from metal-spiked sediments was
      assessed using the midge, Chironomus maddeni. Survival of the larvae was
      significantly reduced at a porewater salinity of 12 g/L, but no effects were
      observed at 4 or 8 g/L. Both growth and survival of C. maddeni were reduced after
      exposure to salt/metal spiked sediments as compared to those exposed to sediments
      spiked with metals or salt alone. Increased salinity resulted in increased
      bioaccumulation of copper and zinc, but decreased bioaccumulation of lead. The
      observed patterns of bioaccumulation were not entirely explained by the modelled
      free ion activities of the metals, indicating that factors such as osmotic
      stress, consumption of metal-contaminated sediments or metal interactions may
      have been important as well. These results highlight the need to consider the
      influence of existing or potential salinization when undertaking hazard
      assessments of freshwater systems impacted by contaminants such as trace metals.

PMID- 16087282
TI  - Primary organic pollutants in New Zealand urban aerosol in winter during high
      PM10 episodes.
AB  - In the two biggest New Zealand cities, Auckland and Christchurch, the mass
      concentration of the PM10 atmospheric aerosol can exceed the 50 microg m(-3) 24 h
      health guideline in winter. This high pollution level is thought to be caused
      mainly by old-fashioned domestic heating systems based on wood combustion.
      Therefore the chemistry of the carbonaceous aerosol has been investigated in
      several high-pollution level urban situations in order to assess the origin of
      the pollution. All the high concentration organic tracers, including levoglucosan
      and dehydroabietic acid, were characteristic for biomass burning. The findings
      have confirmed via advanced chemical analytical methods that domestic heating can
      be the main contributor to the high level of wintertime pollution, especially in
      Christchurch. The results are of great importance in supporting the ambition of
      authorities and environmental associations to change the domestic heating
      regimes.

PMID- 16087283
TI  - In vitro antioxidant activity and scavenging effects of Cinnamomum verum leaf
      extract assayed by different methodologies.
AB  - The free radical scavenging capacity and antioxidant activities of the methanolic
      extract of Cinnamomum verum leaf (CLE) were studied and compared to antioxidant
      compounds like trolox, butylated hydroxyl anisole, gallic acid and ascorbic acid.
      The CLE exhibited free radical scavenging activity, especially against DPPH
      radical and ABTS radical cation. They also exhibited reducing power and metal ion
      chelating activity, along with hydroxyl radical scavenging activity. The
      peroxidation inhibiting activity of CLE recorded using the linoleic acid emulsion
      system, showed very good antioxidant activity.

PMID- 16087284
TI  - Reproductive and neurobehavioural toxicity study of tartrazine administered to
      mice in the diet.
AB  - Tartrazine was given in the diet to provide levels of 0% (control), 0.05%, 0.15%,
      and 0.45% (approximately 83, 259, 773 mg/kg/day, respectively) from five weeks of
      age of the F0 generation to nine weeks of age of the F1 generation in mice, and
      selected reproductive and neurobehavioural parameters were measured. In movement
      activity of exploratory behaviour in the F0 generation, number of vertical
      activity was significantly increased in the middle-dose group in males. There
      were no adverse effects of tartrazine on either litter size, litter weight and
      sex ratio at birth. The average body weight of male offspring was significantly
      increased in the high-dose group and that of female offspring was significantly
      increased in the middle-dose group at birth. In behavioural developmental
      parameters, surface righting at PND 4 was significantly accelerated in the high
      dose group in male offspring, and those effects were significantly dose-related
      in a trend test (P<0.01). Cliff avoidance at PND 7 was significantly accelerated
      in the middle-dose group in male offspring. Negative geotaxis at PND 4 was
      significantly delayed in the high-dose group in female offspring. Other variables
      measured showed no significant adverse effects in either sex in the lactation
      period. In movement activity of exploratory behaviour in the F1 generation,
      number of movement showed a significant tendency to be affected in the treatment
      groups in male offspring in a trend test (P<0.05). The dose level of tartrazine
      in the present study produced a few adverse effects in neurobehavioural
      parameters during the lactation period in mice. Nevertheless, the high-dose level
      were in excess of the ADI of tartrazine (0-7.5 mg/kgbw), and the actual dietary
      intake of tartrazine is presumed to be much lower. It would therefore appear that
      the levels of actual dietary intake of tartrazine is unlikely to produce any
      adverse effects in humans.

PMID- 16087285
TI  - Medical aspects of toxin weapons.
AB  - For centuries, poisons and other biological material have been considered as
      weapons. However, it has been merely 100 years that the use of biological toxins
      as weapons has been explored scientifically. Trichothecenes, ricin and botulinum
      neurotoxins are natural organic toxins with diverse potencies. Their molecular
      structure, mechanisms of action, detection, clinical diagnosis and therapy are
      reviewed and their potential as biological weapon is discussed. It is not only
      the median lethal dose of each toxin that decides on its usability as a
      biological weapon, but also the availability, scale of production, purity of the
      isolated material and route of distribution. In general, without a state
      infrastructure, the use of biological weapons is restricted to assassinations or
      strictly localised terrorist attacks.

PMID- 16087286
TI  - Dental patient awareness of smoking effects on oral health: Comparison of smokers
      and non-smokers.
AB  - OBJECTIVES: The negative effects of cigarette smoking on oral health are well
      established, yet few studies assessed patient awareness of such effects. The aim
      of this study was to examine differences in dental patient knowledge and
      awareness of the effects of smoking on oral health between smokers and non
      smokers. METHODS: Adult patients from 12 dental centers in Kuwait were asked to
      complete a 14-point self-administered structured questionnaire on the effects of
      smoking on oral health in this cross-sectional survey. Significant associations
      between oral health knowledge, smoking status, and sociodemographic variables
      were examined with univariate analysis and logistic regression. RESULTS: A total
      of 1012 subjects participated (response rate = 84.3%). The prevalence of smoking
      was 29.3%. Fewer smokers than non-smokers thought that oral health and smoking
      are related (92.2% vs. 95.8%; P = 0.020), and that smoking affected oral cancer
      (52.4% vs. 66.8%; P < 0.001), periodontal health (72% vs. 78%; P = 0.040), or
      tooth staining (86.1% vs. 90.9%; P = 0.018). Logistic regression analysis showed
      smokers to be significantly less aware of the oral health effects of smoking than
      non-smoking patients (OR=1.51; 95% CI: 1.05-2.16; P = 0.025). CONCLUSION: Smoking
      dental patients are significantly less aware of the oral health effects of
      smoking than non-smokers. Comparative studies in other populations may be
      warranted to ascertain the validity of these results.

PMID- 16087287
TI  - Effect of acidic food and drinks on surface hardness of enamel, dentine, and
      tooth-coloured filling materials.
AB  - OBJECTIVES: The purpose of this study was to determine the effect of acidic food
      and drinks (Cola soft drink, drinking yogurt, orange juice, sports drink, Tom-yum
      soup) on surface hardness of various substrates (enamel, dentine, universal
      composite, microfilled composite, conventional glass ionomer, resin-modified
      glass ionomer, polyacid-modified resin composite). METHODS: Specimens (n = 10)
      were alternately immersed, 5 s each, in food or drinks and in artificial saliva
      for 10 cycles. Baseline and post-immersion Vickers hardness were compared using
      paired t-test. The difference in hardness between the groups was analysed with
      one-way ANOVA followed by a least significant different (LSD) test. RESULTS: Cola
      soft drink significantly reduced surface hardness of enamel, dentine, microfilled
      composite, and resin modified glass ionomer (p < 0.05). Orange juice and sports
      drink significantly reduced surface hardness of enamel (p < 0.05). Drinking
      yogurt and Tom-yum soup did not reduce surface hardness of any substrate.
      CONCLUSION: This in vitro study confirms the erosive potential of certain acidic
      food and drinks that public should be aware of.

PMID- 16087288
TI  - Natural antisense LHCGR could make sense of hypogonadism, male-limited precocious
      puberty and pre-eclampsia.
AB  - The pleiotropic effects of human chorionic gonadotrophin (hCG), the key regulator
      of human pregnancy, are dependent upon cell surface expression of its functional
      cognate receptor LHCGR in the placental trophoblasts, corpus luteum, uterus,
      vascular endothelial and smooth muscle cells. Additionally, lutenizing hormone
      mediated signalling failure has often been linked to activating/inactivating
      mutations in LHCGR. One of the intriguing aspects of these studies is that the
      mutations are most frequently located within C-terminal 200-350 residues of the
      receptor protein. In an attempt to reconcile the mechanistic basis of LHCGR
      regulation and mutations, we have carried out bioinformatic analyses to identify
      the CpG-rich regions and the major potential scaffold/matrix attachment sites
      (S/MARs) in LHCGR and neighbouring gene (ALF) at human chromosome 2p21. Based on
      these analyses, we propose a chromatin-loop model, which may explain the temporal
      regulation and susceptibility to mutation of the human LHCGR. One of the
      characteristic features of the model, is that the major potential S/MAR sequences
      of the human LHCGR gene (68 kb) are located at the 3' end of the gene, and unlike
      mouse, the transmembrane and C-terminal protein coding sequences at exon 11 are
      embedded in this S/MAR site. Moreover, this region is subject to antisense
      transcription from the neighbouring gene ALF, which is gonad-specific and is only
      activated in meiotic spermatocytes and oocytes. Together, these analyses suggest
      that exon 11 of human LHCGR could be more susceptible to mutation than the other
      10 exons together and that activation of LHCGR, contingent to the somatic
      silencing of neighbouring ALF, could be linked to male-limited precocious puberty
      and pre-eclampsia.

PMID- 16087289
TI  - Polycyclic aromatic hydrocarbons degradation by composting in a soot-contaminated
      alkaline soil.
AB  - This study deals with the biodegradation of the polycyclic aromatic hydrocarbons
      (PAH)s present in a soil contaminated by soot waste, characterised by a total
      PAHs content in the 200 mg kg(-1) range. A challenging characteristic of the
      waste soil treated was its high alkalinity, with a pH of about 12.8. The waste
      came from a soot-contaminated area located in the industrial zone of Porto
      Marghera, Venice (Italy). The biodegradation process employed was the composting
      of the waste with sewage sludge and yard waste. The process was carried out on a
      pilot scale using a closed tank with forced aeration for a period of 60 days,
      followed by 70 days with natural aeration. The time evolution of the process was
      monitored by following the time change in the concentration of the 16 US-EPA
      PAHs, as well as temperature, pH, electrical conductivity, C and N contents. Also
      phytotoxicity parameters, such as the growth and respiration indexes, were
      monitored. An induction time of about 30 days was observed, which corresponded to
      the time required before observing a significant self-drop in the waste pH and an
      increase in mass temperature. Afterward, a progressive drop in the PAHs
      concentration was observed, up to reaching after 130 days an overall degradation
      percentage in the order of 68%. The degradation was more effective on rather low
      molecular weight PAHs (2-4 rings).

PMID- 16087290
TI  - Catalytic hydrogenation of polycyclic aromatic hydrocarbons over palladium/gamma
      Al2O3 under mild conditions.
AB  - As a prelude to the optimization of a continuous decontamination system,
      catalytic hydrogenations of selected tri-, tetra- and penta-cyclic aromatic
      hydrocarbon compounds over commercial alumina supported palladium were
      investigated under mild conditions ( approximately 90 degrees C/0.42 MPa H2) and
      interpreted in the light of reports from the literature. Acenaphthylene,
      acenaphthene, anthracene, phenanthrene, chrysene and benzo[alpha]pyrene were
      hydrogenated, virtually completely, to saturated polycyclic hydrocarbon compounds
      with no appreciable evidence of carbon-carbon bond rearrangement during
      equilibration. With comparable operating conditions, triphenylene was only
      partially hydrogenated; the central ring remained unsaturated. The effects of
      reaction temperature, time of equilibration and supporting gases on hydrogenation
      were evaluated. Whereas near-critical CO2 had no perceptible influence on
      rate/course of the reaction, nitrogen decreased the reaction rate somewhat.

PMID- 16087291
TI  - Traumatic injury induced homer-1a gene expression in cultured cortical neurons of
      rat.
AB  - The Homer proteins belong to one of the newly found postsynaptic density protein
      families. As an immediately early gene, the homer-1a is dynamically expressed and
      is upregulated by synaptic activity. The homer-1b/c is constitutively expressed
      and there is no change of gene expression with neuronal activity. In this study,
      we investigated whether a traumatic injury might regulate the homer-1a expression
      in cultured cortical neurons of rat. After 7 days in vitro cultivation, the rat
      fetus cortical neurons were divided into control and injured groups. Then, a
      traumatic injury was performed on a cortical neuronal culture using a punch
      device that consisted of 28 stainless steel blades joined together, these
      produced parallel cuts of 1.2 mm that were uniformly distributed through the cell
      layer. The lactate dehydrogenase level of the neuronal cultures medium was
      evaluated and the expression patterns of homer-1a, homer-1b/c were analyzed with
      the method of RT-PCR and Western blot at different times after the injury (10, 30
      min, 1, 3, 6, 12, 24, 72 h). It was shown that there was no expression of homer
      1a in the control group, but homer-1a was upregulated in the period of 10 min to
      72 h after the traumatic injury. The homer-1b/c was clearly observed in the
      control group, but there was no change in its expression after traumatic
      stimulation. It was concluded that traumatic stimulation could induce the homer
      1a gene expression, dynamically expressed homer-1a and constitutively expressed
      homer-1b/c might modulate the distribution and function of group I metabotropic
      glutamate receptors.

PMID- 16087292
TI  - Novel CLN3 mutation predicted to cause complete loss of protein function does not
      modify the classical JNCL phenotype.
AB  - Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), or Batten disease, is a childhood
      neurodegenerative disease that is characterized clinically by progressive visual
      loss, seizures, dementia, and motor incoordination. Children affected with this
      disease tend to develop normally for the first 5 years of life. However, once
      disease onset occurs, they decline rapidly and die in their late 20s to early
      30s. Though this represents the typical disease course, the onset and severity of
      disease symptoms can vary. This variability is presumed to be the result of both
      differences in the causative genetic mutation in the CLN3 gene as well as
      environmental influences. Most cases of JNCL are caused by a 1 kb deletion in the
      CLN3 gene, resulting in a frameshift mutation predicted to leave the first 153
      amino acids of the CLN3 protein intact, followed by the addition of 28 novel
      amino acids. Here we report the discovery of a novel mutation identified as a G
      to T transversion at nucleotide 49 (G49T) in exon 2 of CLN3, introducing a
      premature stop codon (E17X) near the N-terminus. This mutation represents the
      most 5' mutation described to date. The patient examined in this study was
      heterozygous for the common 1 kb deletion and E17X. She had classical disease
      progression, suggesting that this mutation in CLN3 mimics the more prevalent 1 kb
      deletion and that progression of JNCL is predominantly the result of loss of CLN3
      function.

PMID- 16087293
TI  - Estradiol prevents the injury-induced decrease of Akt activation and Bad
      phosphorylation.
AB  - Estradiol prevents neuronal cell death through the inhibition of apoptotic
      signals and the activation of cell survival signals. This study investigated
      whether estradiol modulates the anti-apoptotic signal through the activation of
      Akt and its downstream targets, including Bad, Bcl-x(L), and 14-3-3. Adult female
      rats were ovariectomied and treated with estradiol prior to middle cerebral
      artery occlusion (MCAO). Brains were collected 24 h after MCAO and infarct
      volumes were analyzed. We confirmed that estradiol significantly reduces infarct
      volume and decreases the positive cells of TUNEL staining in the cerebral cortex.
      Potential activation was measured by phosphorylation of Akt at Ser473 and Bad at
      Ser136 using Western blot analysis. Estradiol prevents the injury-induced
      decrease of pAkt, pBad, and Bcl-x(L). Further, in the presence of estradiol, the
      interaction of pBad and 14-3-3 increased, compared to that of oil-treated
      animals. Our findings suggest that estradiol prevents cell death due to brain
      injury and that Akt activation and Bad phosphorylation by estradiol mediated
      these protective effects.

PMID- 16087294
TI  - Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, exerts
      neuroprotective effects in traumatic brain injury.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) has been
      demonstrated to reduce inflammation in various inflammatory diseases. As
      traumatic brain injury (TBI) caused a neuroinflammatory response, we examined the
      effect of fenofibrate, a PPARalpha agonist, on the post-traumatic consequences
      caused by lateral fluid percussion of brain in rats. The effects of fenofibrate
      (50 and 100mg/kg) were evaluated on the consequences of TBI in the early phase (6
      and 24h) and the late phase (7 days) after TBI. Neurological deficit, brain
      lesion, cerebral oedema and ICAM-1 expression were evaluated. Treatment with
      fenofibrate (given p.o. at 1 and 6h after TBI) decreases the neurological deficit
      induced by TBI at 24h. Furthermore, fenofibrate reduces brain oedema and ICAM-1
      expression at 24h post-TBI. Rats given fenofibrate at 1, 6, 24, 48 and 72h after
      TBI show neurological recovery associated with a reduction of the brain lesion at
      7 days post-TBI. The present data represents the first demonstration that
      fenofibrate, a PPARalpha agonist, exerts neuroprotective effects in TBI. The
      activation of receptor PPARalpha could be beneficial by counteracting the
      deleterious inflammatory response following TBI. This suggests that PPARalpha
      activation could be a new and promising therapeutic strategy for the treatment of
      brain trauma.

PMID- 16087295
TI  - Effects of intradermal foot and forearm capsaicin injections in normal and
      vulvodynia-afflicted women.
AB  - Cutaneous response to capsaicin has been used to assess central sensitization in
      pain research. This study compared the response to intradermal capsaicin in the
      forearm and foot of vulvar vestibulitis (vestibulodynia)-afflicted cases and
      controls. We hypothesized that cases will experience greater spontaneous pain,
      larger cutaneous areas of punctate hyperalgesia and dynamic allodynia, and
      greater vascular flow than controls. We also hypothesized enhanced post-injection
      pain in the foot compared to the forearm based on dermatome proximity of the foot
      and vulva. Methods. Ten vulvar vestibulitis syndrome (VVS) cases and 10 age and
      ethnically matched controls underwent two randomized, cross-over trials with
      intra-dermal injections of capsaicin or a saline placebo in the forearm and foot.
      Outcome measures included spontaneous pain level, surface area of punctate
      hyperalgesia, surface area of dynamic allodynia, cutaneous blood flow, regional
      skin temperature and vital signs. Results. VVS cases experienced greater
      spontaneous pain, punctate hyperalgesia and dynamic allodynia than pain-free
      controls. Within the VVS group, post-capsaicin spontaneous pain, punctate
      hyperalgesia and dynamic allodynia were similar in the forearm and foot. Post
      capsaicin blood flow did not differ between cases and controls by anatomic site.
      Measures of depression and anxiety correlated with spontaneous pain intensity but
      did not correlate with measures of hyperalgesia, allodynia, or blood flow. VVS
      cases had higher resting pulse rates and lower resting systolic blood pressures
      than in controls. Conclusion. VVS patients show enhancement of post-capsaicin
      pain response extending far beyond the anatomic location of the primary
      complaint.

PMID- 16087297
TI  - Cellular adhesive phenomena in apicomplexan parasites of red blood cells.
AB  - The apicomplexan parasites Babesia and Plasmodium are related, yet
      phylogenetically distinct haemoprotozoa that infect red blood cells and cause
      severe diseases of major human and veterinary importance. A variety of cellular
      and molecular interactions are pivotal in many aspects of the pathogenicity of
      these two parasites. Comparison of the cellular and molecular mechanisms that
      culminate in accumulation of parasitised red blood cells in the microvasculature
      of cattle infected with Babesia bovis (babesiosis) and humans infected with
      Plasmodium falciparum (falciparum malaria) is particularly instructive given the
      striking similarities in the pathophysiology of these two important medical and
      veterinary diseases. While such adhesive phenomena have been studied extensively
      in malaria, they have received relatively little attention in babesiosis. In this
      review, we summarise the findings of more than 25 years of research into cellular
      adhesive phenomena in malaria and speculate on how this body of work can now be
      applied to Babesia parasites. Such information is fundamental if we are to learn
      more about the biology of Babesia parasites, the cellular and molecular
      mechanisms by which they cause infection and disease and how to develop novel
      therapeutic strategies or vaccines for both Babesia and malaria infections.

PMID- 16087298
TI  - Voice and swallowing outcomes of an organ-preservation trial for advanced
      laryngeal cancer.
AB  - INTRODUCTION: Organ-preservation treatment approaches for advanced laryngeal
      cancer patients that use combination chemoradiotherapy result in cure rates
      similar to primary laryngectomy with postoperative radiotherapy. In the national
      VA Larynx Cancer Trial, successful organ preservation was associated with an
      overall improvement in quality of life but not in subjective speech compared with
      long-term laryngectomy survivors. As part of a Phase II clinical trial, a
      prospective study of speech and swallowing results was conducted to determine if
      larynx preservation is associated with improved voice and swallowing compared
      with results in patients who require salvage laryngectomy. SUBJECTS: A total of
      97 patients with advanced laryngeal cancer (46 Stage III, 51 Stage IV) were given
      a single course of induction chemotherapy (cisplatin 100 mg/m2 on Day 1 and 5-FU
      1,000 mg/m2/day x 5 days), followed by assessment of response. Patients with less
      than 50% response underwent early salvage laryngectomy, and patients with 50% or
      better response underwent concurrent chemoradiation (72 Gy and cisplatin 100
      mg/m2 on Days 1, 22, and 43), followed by two cycles of adjuvant chemotherapy
      (DDP/5-FU). Direct laryngoscopy and biopsy were performed 8 weeks after radiation
      therapy to determine final tumor response. Late salvage surgery was performed on
      patients with persistent or recurrent disease. METHODS: Completed survey data on
      voice and swallowing utilizing the Voice-Related Quality of Life Measure (V-RQOL)
      and the List Performance Status Scale for Head and Neck Cancer Patients (PSS-HN)
      were obtained from 56 patients who were alive and free of disease at the time of
      survey, with a minimum follow-up of 8 months. Comparisons were made between
      patients with an intact larynx (n = 37) vs. laryngectomy (n = 19), as well as
      early (n = 12) vs. late salvage laryngectomy (n = 7). Multivariate analysis was
      performed to determine factors predictive of voice and swallowing outcomes.
      Overall 3-year determinant survival was 87%, with median follow-up of 40 months.
      RESULTS: Patients with an intact larynx demonstrated significantly higher (p =
      0.02) mean V-RQOL scores (80.3) than did laryngectomy patients (65.4). This
      finding was consistent in the social-emotional (p = 0.007) and physical
      functioning domains (p = 0.03). No differences in V-RQOL scores were found in
      comparisons between early and late salvage laryngectomy. Multiple linear
      regression revealed that predictors of higher total V-RQOL scores include lower T
      stage (p = 0.03), organ preservation (p = 0.0007), and longer duration since
      treatment (p = 0.01). Understandability of speech was better in patients with an
      intact larynx (p = 0.001). Overall swallowing function was comparable between
      groups. Multiple logistic regression revealed that longer duration since
      treatment (p = 0.03, odds ratio = 1.1) and lower maximal mucositis grade (p =
      0.03, odds ratio = 0.3) were predictive of higher likelihood of eating in public.
      Nutritional mode consisting of oral intake alone without nutritional supplements
      was achieved in 88.9% of patients with an intact larynx compared with 64.3% of
      laryngectomees (p = 0.09). CONCLUSIONS: Voice-related quality of life is better
      in patients after chemoradiation therapy compared with salvage laryngectomy.
      Earlier salvage, although known to be associated with fewer surgical
      complications, did not result in improved voice; however, the number of patients
      analyzed is small. Overall swallowing function is good in all patients; however,
      patients with an intact larynx are more likely to obtain nutrition with oral
      intake alone without supplements. Such measures of function and quality of life
      are important endpoints to help judge overall effectiveness as newer, more
      aggressive treatment protocols with added toxicities are developed and evaluated.

PMID- 16087299
TI  - [Efficacy variation of erythromycin and spiramycin on periopathogens in
      aggressive periodontitis. An in vitro comparative study].
AB  - AIMS: Erythromycin (ERY) and spiramycin (SPI) are the most frequently prescribed
      macrolides by dentists. However, the emergence of resistant anaerobic subgingival
      bacteria imposes an increased vigilance. This study aims to compare these
      macrolides efficacy on principal periopathogens. MATERIALS AND METHODS: Twenty
      adult patients with aggressive periodontitis were selected and a total of 60
      samples were taken from subgingival flora. Bacterial strains of Porphyromonas
      gingivalis, Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum,
      Peptostreptococcus micros and Actinobacillus actinomycetemcomitans were isolated
      according to J. Slots's rapid identification method. The susceptibilities to ERY
      and SPI were studied using disk diffusion susceptibility test and minimum
      inhibitory concentration test (MIC test). RESULTS: The efficiency variability of
      ERY and SPI on the 50 isolated anaerobic periopathogens was present either
      interindividually (between different patients) and intra-individually (within the
      same patient). While 68% of the tested anaerobic bacteria were sensitive to SPI
      (22% resistant), only 54% were sensitive to ERY (34% resistant). Although
      moderate, the efficacy of SPI seemed more regular in general than ERY: it's
      variation coefficient (40%) is lower than the ERY one (53%). The 7 A.
      actinomycetemcomitans tested showed all a high resistance. CONCLUSION: In a
      general way, the spectre of activity of SPI is stacked in that of ERY. However,
      this study shows a better and regular activity of SPI on the main tested
      periopathogens. These results are in favour of the use of SPI in periodontology
      when penicillins and doxycycline are not useful because specific problems are
      identified (allergy, pregnancy...).

PMID- 16087300
TI  - [Evaluation of a new E-test method for antimicrobial sensitivity testing of
      Pseudomonas aeruginosa isolates from cystic fibrosis].
AB  - BACKGROUND: Sputum bacteriological analysis of cystic fibrosis (CF) patients
      colonised by Pseudomonas aeruginosa is difficult. The bronchial persistence of
      these bacteria involves phenotypical modifications and the many antibiotic
      treatments result in emergence of multiresistant strains. The aim of this study
      is to evaluate a new fast identification and sensitivity testing method of P.
      aeruginosa and other pathogenic bacteria in sputum of CF patients. It is based on
      applying a gradient of antibiotic (E-test strip) onto an agar plate inoculated
      with the sputum. OBSERVATIONS: 310 sputum, collected from adults and children
      colonised by P. aeruginosa, were analysed by this new method. This method allowed
      a direct reading of the minimal concentration of antibiotic that inhibited the
      totality of Gram-negative strains and the detection of resistant pathogenic
      bacteria inside the ellipse of inhibition. Results obtained by this new method
      were compared with the conventional method for identification and antimicrobial
      sensitivity. CONCLUSION: This new method, studying with CF patient colonised by
      P. aeruginosa, appears interesting, with a sensibility equal or higher than 89%
      in detection of the bacteria and their sensitivity to antibiotics. Furthermore it
      allows a saving of time and simplified results.

PMID- 16087301
TI  - Effect of methyl substitution of benzene on the percutaneous absorption and skin
      irritation in hairless rats.
AB  - The permeation rate and skin retention of benzene and methylbenzenes were
      assessed in vitro using hairless rat skin. The effects of unocclusive dermal
      exposures of these chemicals (15 microl every 2h for 8h a day for 4 days) on the
      transepidermal water loss (TEWL), erythema and skin histopathology were measured
      in CD hairless rats. The expression of IL-1 alpha and TNF-alpha in the skin and
      blood were measured at the end of dermal exposures. The flux of benzene was about
      1.5-, 2.5- and 80-fold higher than toluene, xylene and tetramethyl benzene
      isomers (TMB), respectively, and the values were inversely correlated with
      molecular weight (r(2)=0.7455) and logoctanol-water partition coefficient
      (r(2)=0.7831). The retention of chemicals in stratum corneum (SC) was in the
      order of TMB>xylene>toluene approximately benzene. The TEWL and erythema data
      demonstrated that the irritation was in the following order: TMB>xylene>benzene.
      The histo-pathological examination showed that xylene and TMB induced granulocyte
      infiltration, swelling of the epidermis, and extensive disruption and damage of
      stratum corneum. Likewise, the expression of IL-1 alpha in the blood and TNF
      alpha in the skin after dermal exposures was higher for TMB followed by xylene
      and benzene compared to control. In conclusion, the aromatic hydrocarbon
      chemicals induced cumulative irritation upon low-level repeat exposures for a 4
      day period and the irritation increased with the number of methyl groups of
      benzene. The affinity of the chemical to SC and their gradual accumulation in the
      skin in the present study is the reason for the differences in the skin
      irritation profiles of different aromatic chemicals. Our ultimate goal is to
      develop a biologically based model that connects skin retention of chemical to
      the skin irritation response. The findings of the present study will be helpful
      in understanding the role of these chemicals in the jet fuel and various
      petroleum based fuels in inducing skin irritation response.

PMID- 16087302
TI  - Differences in gene expression patterns between somatic cell nuclear transfer
      embryos constructed with either rabbit granulosa cells or their derivatives.
AB  - Successful production of offspring by somatic cell nuclear transfer (SCNT) is
      affected by the nature of the donor cells used. The purpose of this study was to
      determine whether characteristic changes induced in donor cells by culture
      conditions influenced gene expression patterns in the resultant SCNT embryos.
      Rabbit granulosa cells (rGC) were cultured under different conditions, either
      with or without hCG, and the two derivative cell types obtained (named
      respectively cGC+ and cGC-) were used as donor cells for SCNT. There were
      characteristic differences between fresh rGC and the two derivative cell types:
      p450scc expression and progesterone secretion were both higher in cGC+ than in
      cGC-; expression of bmp4 and fgfr2 was decreased in cGC+ and cGC- compared with
      rGC; and cGC+ and cGC- cell types gained collagenIV expression. Use of fresh rGC,
      or cGC+ and cGC- derivative cells, did not alter either the developmental
      potencies of SCNT oocytes or cell numbers at the blastocyst stage. The expression
      patterns of four genes (bmp4, fgfr2, gata4, oct3/4) in SCNT embryos and in
      fertilized embryos were analyzed by quantitative RT-PCR. We found that oct3/4 was
      expressed in all embryos. The expression patterns of the other three genes showed
      considerable variation between the different types of embryo: bmp4 was found in
      most fertilized embryos but only some of rGC and none of cGC+ and cGC- derived
      SCNT embryos; fgfr2 was present in fertilized embryos but was present in some rGC
      and cGC- NT embryos and in all cGC+ NT embryos; gata4 was not expressed in
      fertilized embryos but was present in a few rGC and cGC+ NT embryos and in most
      cGC- NT embryos. Our results suggest that the gene expression patterns in SCNT
      embryos derived from granulosa donor cells are affected by characteristic changes
      to the cells during in vitro culture.

PMID- 16087303
TI  - Mechanistic studies on the decomposition of sodium cyanide in aqueous solution
      and in the solid state.
AB  - The mechanism of the spontaneous decomposition of sodium cyanide in aqueous
      solution and in the solid state was studied by ion chromatography (IC), FT-Raman
      spectroscopy, gas chromatography/mass spectrometry (GC/MS), and carbon-13 nuclear
      magnetic resonance spectroscopy (13C NMR). In the aqueous solution, gradual
      decomposition of the cyanide to carbonate by a displacement reaction was
      observed. In the solid state, sodium cyanide was found to be stable when kept in
      dry air, however, it decomposed by the same mechanism as that in aqueous solution
      under non-dry conditions.

PMID- 16087304
TI  - Flunitrazepam: psychomotor impairment, agitation and paradoxical reactions.
AB  - Benzodiazepines are sedatives used for anxiolysis, hypnosis, muscle relaxation
      and the treatment of epilepsy. Paradoxical reactions including agitation,
      talkativeness, confusion, disinhibition, aggression, violent behavior and loss of
      impulse control may, however, occur in some subjects. It has been claimed that
      high doses of flunitrazepam may cause aggression on a more regular basis in all
      individuals. The present study makes use of a Norwegian forensic toxicological
      database containing analytical results from drivers suspected of driving under
      the influence and suspects of violent crime to analyze the relationship between
      behavior and blood flunitrazepam concentration. Four-hundred and fifteen cases of
      drivers suspected of driving under the influence and seven cases of suspects of
      violent crime were studied. These selected cases had flunitrazepam as the only
      drug in blood samples and had been evaluated by a clinical test for impairment
      (CTI) performed by a police physician at the time of blood sampling. The impaired
      drivers had higher blood flunitrazepam concentrations than the not impaired
      drivers. Multivariate analysis revealed that both blood flunitrazepam
      concentration and age of the suspected drivers had independent impact on
      impairment, indicating tolerance with age. Most of the effects measured were
      sedative effects of flunitrazepam and these effects were related to flunitrazepam
      level. Possible paradoxical reactions were observed in a subgroup of 23
      individuals (6%), but these reactions did not relate to blood flunitrazepam
      concentration. The suspects of violent crime showed similar degree impairment and
      had not more paradoxical reactions than the suspected drugged drivers. The
      findings were in agreement with other research that claims paradoxical reactions
      should be viewed as a reaction in certain individuals, and does not support the
      notion that flunitrazepam in high concentration produces aggression in all
      individuals taking the drug.

PMID- 16087305
TI  - Expressional and functional studies of Wolframin, the gene function deficient in
      Wolfram syndrome, in mice and patient cells.
AB  - Wolfram Syndrome is an autosomal recessive degenerative disorder of the
      neuroendocrine system. Diabetes mellitus is its lead symptom. Patients show
      mutations in the wolframin (WFS1) gene coding for a hydrophobic transmembrane
      protein of 890 amino acids. This protein was preliminarily localised in the
      endoplasmatic reticulum (ER) in cells of mice and rats. Mice lacking the WFS1
      gene display degeneration of pancreatic beta-cells following induction of ER
      stress. We here used antibodies against substructures of the wolframin protein in
      order to analyse its expression and localisation. Expression was detected in both
      pancreatic beta-cells and the limbic system of mice. Using the rat insulinoma
      cell line RIN 5AH and fractionated mouse brain tissue, we confirmed wolframin
      localisation to the endoplasmic reticulum. Expression profiling on patient's
      primary fibroblasts revealed down-regulation of the diabetes associated plasma
      membrane glycoprotein (PC-1) gene, and up-regulation of fibulin-3, a gene
      connected to senescence. However, cell proliferation was indistinguishable from
      non-mutated cells. In contrast to data obtained on murine pancreatic islets, we
      found no increased apoptosis following induction of ER stress but rather by
      staurosporine treatment in the absence of WFS1 function. This indicates a new
      role of WFS1 deficiency in programmed cell death.

PMID- 16087306
TI  - Mice and flies and monkeys too: caloric restriction rejuvenates the aging immune
      system of non-human primates.
AB  - Humanity has been obsessed with extending life span and reversing the aging
      process throughout recorded history and this quest most likely preceded the
      invention of the written word. The search for eternal youth has spurred holy wars
      and precipitated the discovery of the new world (the 'Fountain of youth'). It
      therefore comes as no surprise that an increasingly greater amount of research
      effort is dedicated to improve our understanding of the aging process and finding
      interventions to moderate its impact on health. Caloric restriction (CR) is the
      only intervention in biology that consistently extends maximal and median life
      span in a variety of short-lived species. Several theories to explain the
      mechanisms of action of CR have been put forth, including the possibility that CR
      acts by retarding immune senescence. The question remains, however, whether CR
      will have the same beneficial impact on human aging, and, if so, how long does CR
      need to last to produce beneficial effects. To address this question, several
      groups initiated long-term studies in Rhesus macaques (RM) in the 1980s. Here, we
      review published data describing the impact of CR on the aging immune system of
      mice and primates, and discuss our unpublished data that delineate similarities
      and differences in the effects of CR upon T cell aging and homeostasis between
      these two models.

PMID- 16087307
TI  - Establishment of a Fast Chemical Identification System for screening of
      counterfeit drugs of macrolide antibiotics.
AB  - A Fast Chemical Identification System (FCIS) consisting of two colour reactions
      based on functional groups in molecules of macrolide antibiotics and two TLC
      methods was developed for screening of fake macrolide drugs. The active
      ingredients could be extracted from their oral preparations by absolute alcohol.
      Sulfuric acid reaction as a common reaction of macrolides was first used to
      distinguish the macrolides from other types of drugs and then 16-membered
      macrolides and 14-membered ones were distinguished by potassium permanganate
      reactions depending on the time of loss of colour in the test solution; after
      which a TLC method carried out on a GF(254) plate (5 cm x 10 cm) was chosen to
      further identification of the macrolides. The mobile phase A consisting of ethyl
      acetate, hexane and ammonia (100:15:15, v/v) was used for the identification of
      14-membered macrolides, and the mobile phase B consisting of trichloromethane,
      methanol and ammonia (100:5:1, v/v) was used for the identification of 16
      membered ones. A suspected counterfeit macrolide preparation can be identified
      within 40 min. The system can be used under different conditions and has the
      virtues of robustness, simplicity and speed.

PMID- 16087308
TI  - High-performance liquid chromatography-atmospheric pressure chemical ionisation
      mass spectrometry determination of zaleplon in human plasma.
AB  - A sensitive and specific liquid chromatography-atmospheric pressure chemical
      ionisation-mass spectrometry (LC-APCI-MS) method has been developed and validated
      for the identification and quantification of zaleplon in human plasma using
      estazolam as an internal standard (IS). After the addition of estazolam and 2.0 M
      sodium hydroxide solution, plasma samples were extracted with ethyl acetate and
      then the organic layer was evaporated to dryness. The reconstituted solution of
      the residue was injected onto a prepacked Shim-pack VP-ODS C18 (250 mm x 2.0 mm
      i.d.) column and chromatographed with a mobile phase comprised of methanol:water
      (70:30) at a flow-rate of 0.2 ml/min. Detection was performed on a single
      quadrupole mass spectrometer by selected ion monitoring (SIM) mode via
      atmospheric pressure chemical ionization (APCI) source. The mean standard curve
      was linear (r = 0.9991) over the concentration range of 0.2-100 ng/ml and had
      good back-calculated accuracy and precision. The intra-day and inter-day
      precisions were within 10% relative standard deviation and accuracy ranged from
      85% to 115%. The limit of detection was 0.1 ng/ml. The validated LC-APCI-MS
      method has been used successfully to study zaleplon pharmacokinetic,
      bioavailability and bioequivalence in 18 adult volunteers.

PMID- 16087309
TI  - Sensitive and specific liquid chromatographic-tandem mass spectrometric assay for
      atropine and its eleven metabolites in rat urine.
AB  - A sensitive and specific method is described for the simultaneous determination
      of atropine and its metabolites in rat urine by combining liquid chromatography
      and tandem mass spectrometry (LC-MS(n)). Various extraction techniques (free
      fraction, acid hydrolyses and enzyme hydrolyses) and their comparison were
      carried out for investigation of the metabolism of atropine. After extraction
      procedure the pretreated samples were separated on a reversed-phase C18 column
      using a mobile phase of methanol/ammonium acetate (2 mM, adjusted to pH 3.5 with
      formic acid) (70: 30,v/v) and detected by an on-line LC-MS(n) system.
      Identification and structural elucidation of the metabolites were performed by
      comparing their changes in molecular masses (DeltaM), retention-times and full
      scan MS(n) spectra with those of the parent drug. The results revealed that at
      least eleven metabolites (N-demethyltropine, tropine, N-demethylatropine, p
      hydroxyatropine, p-hydroxyatropine N-oxide, glucuronide conjugates and sulfate
      conjugates of N-demethylatropine, p-hydroxyatropine and the parent drug) and the
      parent drug existed in rat urine after ingesting 25 mg/kg atropine. p
      Hydroxyatropine and the parent drug were detected in rat urine for up 106 h after
      ingestion of atropine.

PMID- 16087310
TI  - Antioxidant effects of water-soluble fullerene derivatives against ultraviolet
      ray or peroxylipid through their action of scavenging the reactive oxygen species
      in human skin keratinocytes.
AB  - Chemically generated hydroxyl radicals were scavenged by PEG-modified fullerene,
      hydroxy-fullerene and isostearate-mixed fullerene as efficiently as ascorbic acid
      (Asc) or its 2-O-phosphorylated derivative (A2P) as shown by the DMPO-spin
      trap/ESR method. Enzymatically generated superoxide anion radicals were also
      scavenged by PEG-modified or PVP-entrapped fullerene similarly as done by Asc or
      A2P. Some reactive oxygen species (ROS) such as hydroperoxides and hydrogen
      peroxides were generated preferably in the nuclei of UVB-irradiated human skin
      keratinocytes HaCaT, and repressed by PVP- or gamma-cyclodextrin-fullerene. In
      contrast, the cytoplasm in the keratinocytes accumulated the ROS that were
      generated by the peroxylipid model compound t-BuOOH, and underwent the ROS
      repression by PVP-fullerene more markedly than by A2P. Thus several fullerene
      derivatives, especially PVP-fullerene, were shown to diminish the ROS amounts in
      terms of the molecular and cellular levels against either UVB or t-BuOOH,
      suggesting the expectation for development as rejuvenation cosmetics.

PMID- 16087311
TI  - Development of the WAIS-III estimate of premorbid ability for Canadians (EPAC).
AB  - This study developed regression algorithms for estimating IQ scores using the
      Canadian WAIS-III norms. Participants were the Canadian WAIS-III standardization
      sample (n = 1,105). The sample was randomly divided into two groups (Development
      and Validation groups). The Development group was used to generate 12 regression
      algorithms for FSIQ and three algorithms each for VIQ and PIQ. Algorithms
      combined demographic variables with WAIS-III subtest raw scores. The algorithms
      accounted for 48-78% of the variance in FSIQ, 70-71% in VIQ, and 45-55% in PIQ.
      In the Validation group, the majority of the sample had predicted IQs that fell
      within a 95% CI band (FSIQ=92-94%; VIQ=93-95%; PIQ=94-94%). These algorithms
      yielded reasonably accurate estimates of FSIQ, VIQ, and PIQ in this healthy adult
      population. It is anticipated that these algorithms will be useful as a means for
      estimating premorbid IQ scores in a clinical population. However, prior to
      clinical use, these algorithms must be validated for this purpose.

PMID- 16087312
TI  - An updated review of the long-term neurological effects of galactosemia.
AB  - Classical galactosemia is an autosomal recessive condition in which there is near
      total absence of the activity of galactose-1-phosphate uridyltransferase.
      Patients with this condition have substantial motor, cognitive, and psychiatric
      impairments despite dietary treatment. A characteristic pattern of biochemical
      abnormalities is observed in patients with this disorder. Galactose-1-phosphate,
      the substrate of galactose-1-phosphate uridyltransferase, accumulates within
      cells, and surplus galactose is reduced to galactitol or oxidized to galactonate.
      Using sophisticated mass spectrometry, these compounds as well as free galactose
      can be measured in plasma and in urine. It is clear that initiation of dietary
      restriction of galactose in the newborn period produces reversal of hepatic,
      renal, brain, and immune dysfunction, along with reduction of the accumulated
      galactose metabolites. However, the neurologist should be aware that chronic and
      progressive neurologic impairments occur even in patients spared these neonatal
      symptoms. The purpose of this review is to summarize current information about
      neurologic complications of galactosemia and what is known, and still unknown,
      about its pathophysiology.

PMID- 16087313
TI  - Broadcast scheduling in wireless multihop networks using a neural-network-based
      hybrid algorithm.
AB  - In wireless multihop networks, the objective of the broadcast scheduling problem
      is to find a conflict free transmission schedule for each node at different time
      slots in a fixed length time cycle, called TDMA cycle. The optimization criterion
      is to find an optimal TDMA schedule with minimal TDMA cycle length and maximal
      node transmissions. In this paper we propose a two-stage hybrid method to solve
      this broadcast scheduling problem in wireless multihop networks. In the first
      stage, we use a sequential vertex-coloring algorithm to obtain a minimal TDMA
      frame length. In the second stage, we apply the noisy chaotic neural network to
      find the maximum node transmission based on the results obtained in the previous
      stage. Simulation results show that this hybrid method outperforms previous
      approaches, such as mean field annealing, a hybrid of the Hopfield neural network
      and genetic algorithms, the sequential vertex coloring algorithm, and the gradual
      neural network.

PMID- 16087314
TI  - Cross-entropy embedding of high-dimensional data using the neural gas model.
AB  - A cross-entropy approach to mapping high-dimensional data into a low-dimensional
      space embedding is presented. The method allows to project simultaneously the
      input data and the codebook vectors, obtained with the Neural Gas (NG) quantizer
      algorithm, into a low-dimensional output space. The aim of this approach is to
      preserve the relationship defined by the NG neighborhood function for each pair
      of input and codebook vectors. A cost function based on the cross-entropy between
      input and output probabilities is minimized by using a Newton-Raphson method. The
      new approach is compared with Sammon's non-linear mapping (NLM) and the
      hierarchical approach of combining a vector quantizer such as the self-organizing
      feature map (SOM) or NG with the NLM recall algorithm. In comparison with these
      techniques, our method delivers a clear visualization of both data points and
      codebooks, and it achieves a better mapping quality in terms of the topology
      preservation measure q(m).

PMID- 16087315
TI  - Rich dynamics of pulse-coupled spiking neurons with a triangular base signal.
AB  - This paper presents a spiking neuron circuit with a triangular base signal. The
      circuit can output rich pulse-trains and the dynamics can be analyzed using a
      piecewise linear one-dimensional pulse-position map. Applying cross-switching to
      two neurons we construct a pulse-coupled system whose dynamics can be integrated
      into a composite map of the pulse position maps of two neurons. The composite map
      is piecewise linear and precise analysis is possible. We can clarify various
      interesting phenomena caused by the pulse-coupling. For example, periodic
      behavior of each neuron is changed into chaotic behavior and chaotic behavior of
      each neuron is changed into periodic behavior. These results provide basic
      information to construct flexible pulse-coupled neural networks.

PMID- 16087316
TI  - A mixed analog/digital chaotic neuro-computer system for quadratic assignment
      problems.
AB  - We construct a mixed analog/digital chaotic neuro-computer prototype system for
      quadratic assignment problems (QAPs). The QAP is one of the difficult NP-hard
      problems, and includes several real-world applications. Chaotic neural networks
      have been used to solve combinatorial optimization problems through chaotic
      search dynamics, which efficiently searches optimal or near optimal solutions.
      However, preliminary experiments have shown that, although it obtained good
      feasible solutions, the Hopfield-type chaotic neuro-computer hardware system
      could not obtain the optimal solution of the QAP. Therefore, in the present
      study, we improve the system performance by adopting a solution construction
      method, which constructs a feasible solution using the analog internal state
      values of the chaotic neurons at each iteration. In order to include the
      construction method into our hardware, we install a multi-channel analog-to
      digital conversion system to observe the internal states of the chaotic neurons.
      We show experimentally that a great improvement in the system performance over
      the original Hopfield-type chaotic neuro-computer is obtained. That is, we obtain
      the optimal solution for the size-10 QAP in less than 1000 iterations. In
      addition, we propose a guideline for parameter tuning of the chaotic neuro
      computer system according to the observation of the internal states of several
      chaotic neurons in the network.

PMID- 16087317
TI  - Modelling divided visual attention with a winner-take-all network.
AB  - Experimental evidence on the distribution of visual attention supports the idea
      of a spatial saliency map, whereby bottom-up and top-down influences on attention
      are integrated by a winner-take-all mechanism. We implement this map with a
      continuous attractor neural network, and test the ability of our model to explain
      experimental evidence on the distribution of spatial attention. The majority of
      evidence supports the view that attention is unitary, but recent experiments
      provide evidence for split attentional foci. We simulate two such experiments.
      Our results suggest that the ability to divide attention depends on sustained
      endogenous signals from short term memory to the saliency map, stressing the
      interplay between working memory mechanisms and attention.

PMID- 16087318
TI  - A hierarchical classifier using new support vector machines for automatic target
      recognition.
AB  - A binary hierarchical classifier is proposed for automatic target recognition. We
      also require rejection of non-object (non-target) inputs, which are not seen
      during training or validation, thus producing a very difficult problem. The SVRDM
      (support vector representation and discrimination machine) classifier is used at
      each node in the hierarchy, since it offers good generalization and rejection
      ability. Using this hierarchical SVRDM classifier with magnitude Fourier
      transform (|FT|) features, which provide shift-invariance, initial test results
      on infra-red (IR) data are excellent.

PMID- 16087319
TI  - Use of oral nutritional supplements in patients with Huntington's disease.
AB  - OBJECTIVE: This study assessed the effect of oral nutritional supplements on the
      nutritional status of patients with Huntington's disease. METHODS: This was an
      experimental, longitudinal, prospective study of 30 patients with Huntington's
      disease. We performed neurologic evaluation and dietary assessment and measured
      anthropometric indexes and biochemical indicators; in addition, patients were
      questioned about their weight, appetite, chewing difficulty, and dysphagia.
      Patients consumed two cans daily of a nutritional supplement that contributed an
      extra 473 kcal to their diet for a 90-d period. At the study's end, the
      supplement was suspended and the same variables were reassessed. RESULTS: After
      90 d, 68.7% of patients had increased body weight, 68.7% had ideal body weight
      percentages and body mass indexes, 53.3% had increased midarm circumferences, and
      60.0% had increased arm muscle circumferences and body fat percentages; these
      changes were statistically significant (P < 0.05). The neurologic evaluation
      subscales and the biochemical indicators did not change significantly. With
      regard to subjective variables, patients who reported losing weight during the 3
      mo before the study did not lose more weight and patients who reported having an
      increased appetite before the study remained stable during the study.
      CONCLUSIONS: The nutritional intervention stabilized or slightly improved the
      anthropometric variables assessed; however, no significant change in body mass
      index occurred in 87% of patients. For the purpose of maintaining an acceptable
      nutritional status in patients who have Huntington's disease and normal
      nutritional status, we suggest oral nutritional supplements that contribute an
      average of 473 kcal/d in addition to a normal diet.

PMID- 16087320
TI  - Membrane properties of cationic liposomes composed of
      dipalmitoylphosphatidylcholine and dipalmityldimethylammonium bromide.
AB  - Cationic liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and
      dipalmityldimethylammmonium bromide (DPAB) were prepared by the Bangham method
      and the effect of DPAB on the membrane properties was examined in terms of
      liposomal shape, particle size, trapping efficiency, surface potential and
      dispersibility. The dispersibility of the mixed DPPC/DPAB liposomes (the mole
      fraction of DPAB (XDPAB)>==0.05) was excellent and the dispersibility was
      maintained for 6 months, since the zeta-potential of the mixed liposomes was
      approximately +40 mV. The trapping efficiency of the mixed DPPC/DPAB liposomes
      (XDPAB=0.05) was 10 times greater than that of the DPPC liposomes, and the value
      was largest among the mixed liposomes (XDPAB=0-1.0). Freeze-fracture electron
      micrographs indicated that the shape of the mixed DPPC/DPAB liposomes
      (XDPAB=0.05) was that of large unilamellar vesicles (LUVs) with a diameter of
      approximately 2 microm, while the shape of the DPPC liposomes was that of
      multilamellar vesicles (MLVs). The mixed liposomes had, therefore, a high
      trapping efficiency. Furthermore, the shape of the mixed DPPC/DPAB liposomes
      (XDPAB=0.75) was also that of LUVs with a diameter of approximately 2 microm and
      these had a high trapping efficiency. Whereas, the particle size (500 nm) of the
      mixed DPPC/DPAB liposomes (XDPAB=0.25) was smaller than that of the former and
      had the minimum trapping efficiency. The phase transition temperature of the
      liposomal bilayer membranes indicated a maximum value at 0.25-0.30 mole fractions
      of DPAB. These facts were considered to be due to the fact that DPPC and DPAB,
      whose molar ratio was 7.5:2.5, were tightly packed in the liposomal bilayer
      membranes and that the curvature of the liposomal particle was resultantly large.
      Nevertheless, LUVs having a high trapping efficiency were easily obtained by
      mixing a small amount of DPAB with the DPPC.

PMID- 16087321
TI  - Bupivacaine salts of diflunisal and other aromatic hydroxycarboxylic acids:
      aqueous solubility and release characteristics from solutions and suspensions
      using a rotating dialysis cell model.
AB  - In the search for poorly soluble bupivacaine salts potentially enabling prolonged
      postoperative pain relief after local joint administration in the form of
      suspensions the solubility of bupivacaine salts of diflunisal and other aromatic
      hydroxycarboxylic acids were investigated together with the release
      characteristics of selected 1:1 salts from solutions and suspensions using a
      rotating dialysis cell model. The poorest soluble bupivacaine salts were obtained
      from the aromatic ortho-hydroxycarboxylic acids diflunisal, 5-iodosalicylic acid,
      and salicylic acid (aqueous solubilities: 0.6-1.9 mM at 37 degrees C). Diffusant
      appearance rates in the acceptor phase upon instillation of solutions of various
      salts in the donor cell applied to first-order kinetics. Calculated permeability
      coefficients for bupivacaine and the counterions diflunisal, 5-iodosalicylic
      acid, and mandelic acid were found to be correlated with the molecular size of
      the diffusants. Release experiments at physiological pH involving suspensions of
      the bupivacaine-diflunisal salt revealed that at each sampling point the
      diflunisal concentration exceeded that of bupivacaine in the acceptor phase.
      However, after an initial lag period, a steady state situation was attained
      resulting in equal and constant fluxes of the two diffusants controlled by the
      permeability coefficients in combination with the solubility product of the salt.
      Due to the fact that the saturation solubility of the bupivacaine-salicylic acid
      salt in water exceeded that of bupivacaine at pH 7.4, suspensions of the latter
      salt were unable to provide simultaneous release of the cationic and anionic
      species at pH 7.4. The release profiles were characterised by a rapid release of
      salicylate accompanied by a much slower appearance of bupivacaine in the acceptor
      phase caused by precipitation of bupivacaine base from the solution upon
      dissolution of the salt in the donor cell.

PMID- 16087322
TI  - Transport of anti-allergic drugs across the passage cultured human nasal
      epithelial cell monolayer.
AB  - The purpose of this study was to investigate the nasal absorption characteristics
      of a series of anti-allergic drugs across the human nasal epithelial cell
      monolayer, which was passage cultured by the liquid-covered culture (LCC) method
      on Transwell. Characterization of this cell culture model was achieved by
      bioelectric measurements and morphological studies. The passages 2--4 of cell
      monolayers exhibited the TEER value of 1731+/-635 Omega cm(2) after 2 days of
      seeding and maintained high TEER value for 4--6 days. Morphological study by TEM
      and SEM showed the existence of the tight junctions, and the cuboidal shaped
      epithelial cells monolayer. A series of anti-allergic drugs, albuterol
      hemisulfate, albuterol, fexofenadine HCl, dexamethasone, triamcinolon acetonide,
      and budesonide were selected as model compounds for transport studies. All the
      drugs were assayed using reversed-phase HPLC under isocratic conditions. Results
      indicated that within the logP (apparent 1-octanol/water partition coefficient)
      range from --1.58 (albuterol) to 3.21 (budesonide), there existed 100-fold
      difference in the apparent permeability coefficients (P(app)). A log-linear
      relationship was shown between the drug logP and the P(app) across passaged human
      nasal epithelial monolayers. The amount of fexofenadine HCl and dexamethasone
      across passaged human nasal cell monolayers was concentration-dependent in the
      direction of apical to basolateral. The direction dependent transport studies
      were investigated among all these drugs and no significant difference in the two
      directions was observed. In conclusion, this LCC passaged human nasal epithelial
      culture model may be a useful in vitro model for studying the passive transport
      processes in nasal drug delivery.

PMID- 16087323
TI  - Disorder and dissolution enhancement: deposition of ibuprofen on to insoluble
      polymers.
AB  - Microcrystalline cellulose (MCC) and cross-linked polyvinylpyrrolidone (PVP-CL)
      were examined as polymeric carriers to support amorphous ibuprofen (IB).
      Drug/carrier systems were prepared as physical mixes, and drug was loaded onto
      the polymers by hot mix and solvent deposition methods. The systems were examined
      using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRD)
      and by dissolution testing. PVP-CL reduced drug crystallinity more than MCC and,
      surprisingly, even very simple mixing of ibuprofen with PVP-CL induced
      disordering of the drug. Increased ibuprofen dissolution rates were achieved with
      both polymers, in the order of solvent deposition>hot mixes>physical mixes. The
      increased dissolution rates could be attributed to a combination of faster
      dissolution from amorphous ibuprofen, microcrystalline drug deposition on carrier
      surfaces and polymer swelling. However, no clear relationship was observed
      between ibuprofen dissolution rates (using first order, Higuchi or Hixson-Crowell
      relationships) and drug crystallinity.

PMID- 16087324
TI  - Preparation and evaluation of glibenclamide-polyglycolized glycerides solid
      dispersions with silicon dioxide by spray drying technique.
AB  - Solid dispersions (SDs) of glibenclamide (GBM); a poorly water-soluble drug and
      polyglycolized glycerides (Gelucire with the aid of silicon dioxide (Aerosil
      200); as an adsorbent, were prepared by spray drying technique. SDs and spray
      dried GBM in comparison with pure GBM and corresponding physical mixtures (PMs)
      were initially characterized and then subjected to ageing study up to 3 months.
      Initial characterization of SDs and spray dried GBM by DSC and XRPD showed that
      GBM was present in its amorphous form (AGBM). Improvement in the solubility and
      dissolution rate was observed for all samples. DRIFT spectroscopy revealed
      presence of hydrogen bonding in SDs. During ageing study, almost no decrease of
      in vitro drug dissolution was observed, over the period of 3 months as compare
      with freshly prepared SDs. Slight crystallinity in SDs was observed in the DSC
      and XRPD studies during ageing. Moreover in vivo study in Swiss Albino mice also
      justified the improvement in the therapeutic efficacy of amorphous GBM in SDs
      over pure GBM. Thus, present study demonstrated the high potential of spray
      drying technique for obtaining stable free flowing SDs of poorly water-soluble
      drugs using polyglycolized glycerides carriers with the aid of silicon dioxide as
      an adsorbent.

PMID- 16087325
TI  - Neural pattern dynamics in an oscillator model of the thalamo-reticular system.
AB  - One of development issues for information processing with synchronous
      oscillations in the brain is how new information is coded and how a comparison
      with already existing information is performed. In the present work we study a
      simple neural network model of the thalamo-reticular system based on the Wilson
      Cowan model of neuronal oscillatory behavior. Our results show that both cortical
      control over the thalamus and external sensory input are essential in
      coordinating and generating spatio-temporal patterns of synchronous activity. A
      main finding of the numerical simulations is that the network connectivity and
      the intrinsic oscillatory properties of the neurons result in distinct collective
      behaviors within the network. By varying the connectivity schemes comparable with
      lesionated or damaged brain regions our results are in good agreement with in
      vivo experimental results. Suppressing the sensory input results in temporal
      oscillatory activity in the beta and gamma range and a strong spatial dependence
      of the network activity.

PMID- 16087326
TI  - Interaction of pathogenic fungi with host cells: Molecular and cellular
      approaches.
AB  - This review provides an overview of several molecular and cellular approaches
      that are likely to supply insights into the host-fungus interaction. Fungi
      present intra- and/or extracellular host-parasite interfaces, the parasitism
      phenomenon being dependent on complementary surface molecules. The entry of the
      pathogen into the host cell is initiated by the fungus adhering to the cell
      surface, which generates an uptake signal that may induce its cytoplasmatic
      internalization. Furthermore, microbial pathogens use a variety of their surface
      molecules to bind to host extracellular matrix (ECM) components to establish an
      effective infection. On the other hand, integrins mediate the tight adhesion of
      cells to the ECM at sites referred to as focal adhesions and also play a role in
      cell signaling. The phosphorylation process is an important mechanism of cell
      signaling and regulation; it has been implicated recently in defense strategies
      against a variety of pathogens that alter host-signaling pathways in order to
      facilitate their invasion and survival within host cells. The study of signal
      transduction pathways in virulent fungi is especially important in view of their
      putative role in the regulation of pathogenicity. This review discusses fungal
      adherence, changes in cytoskeletal organization and signal transduction in
      relation to host-fungus interaction.

PMID- 16087327
TI  - MIC and other NKG2D ligands: from none to too many.
AB  - NKG2D, a prime activatory receptor on human NK, CD8(+) alphabeta and gammadelta
      cells, has a variety of ligands, which, despite sharing membership of the MHC
      class I structural club, display an array of unique features. Chronologically,
      human MIC molecules were the first NKG2D ligands to be identified. Then came
      RAET1 (ULBP) molecules, which were identified in both man and mouse, as well as
      H60 and MULT1, which have no counterparts in man to date. The question remains as
      to why, more than how, the evolutionary conserved, apparently monomorphic, single
      copy, NKG2D, can/should adapt to this variety of ligands, and when it does, what
      is the evolutionary advantage of this profusion of ligands for a single receptor?

PMID- 16087328
TI  - Karyometry in the early detection and chemoprevention of intraepithelial lesions.
AB  - The ideal chemopreventive agent targets pre-neoplastic changes and
      intraepithelial neoplasia, preventing progression over time without notable side
      effects. Assessment of success of chemopreventive intervention in the short and
      medium term remains a challenge, and in this review the suggestion is
      investigated that karyometric measurements constitute suitable markers of
      chemopreventive efficacy. Karyometry provides the sensitivity required to detect
      small differences amidst relatively high biological variability. It can help
      establish progression curves of intraepithelial neoplasia (IEN) to invasive
      cancer, and thus detect chemopreventive effects. Such effects can be observed in
      two ways, at the group level (intervention vs. placebo), and at the case (or
      patient) level. The latter is more difficult to establish, necessitating the
      development of specialised statistical methods. Analysis of between-case and
      within-case heterogeneity can reveal useful information about cancer progression
      and prevention. We suggest that karyometry can objectively quantify IEN
      progression, providing a framework for statistically securing chemopreventive
      effects. It can act as an integrating biomarker by detecting chemopreventive
      activity even when the mechanism for a given progression pathway is unknown, or
      when multiple pathways exist. The sensitivity of karyometric detection can help
      optimise the design of clinical trials of novel chemopreventive agents by
      decreasing trial duration and/or sample size.

PMID- 16087329
TI  - Inhibition of survival signalling by dietary polyphenols and indole-3-carbinol.
AB  - Epidemiological studies have long hinted at the possibility that what we eat
      greatly influences our state of health, in particular our relative risk of
      developing cancer. In recent years there has been an exponential increase in the
      number of studies investigating how individual components of the diet interact at
      the molecular level to determine the fate of a cell. It is now apparent that many
      such molecules can preferentially inhibit the growth of tumour cells, by inducing
      cell cycle arrest or apoptosis. The number of signalling pathways and molecular
      targets involved is continually expanding. Consequently, the picture is becoming
      ever more complicated, not least because results often appear to be cell-type
      specific, dose-response relationships are critical, and any one agent appears to
      have multiple mechanisms of action. In addition most studies have been conducted
      in cell culture, often with physiologically unachievable concentrations of single
      agents, making extrapolation to the clinical situation difficult. In this review
      the mechanisms of action of a few well-studied dietary polyphenols (curcumin,
      epigallocatechin gallate and resveratrol) and indole-3 carbinol are considered in
      the light of these issues.

PMID- 16087330
TI  - HRT and breast cancer: impact on population risk and incidence.
AB  - This study has calculated the potential impact of hormone replacement therapy
      (HRT) on breast cancer incidence in Australia and has estimated how changes in
      prescribing HRT to women could affect this risk. The effects of HRT on breast
      cancer incidence was estimated using the attributable fraction technique with
      prevalence data derived from the 2001 Australian Health Survey and published
      rates of breast cancer relative risks from HRT use. In Australia, 12% of adult
      women were current HRT users and in 2001, 11783 breast cancers were reported. Of
      these, 1066 (9%) were potentially attributable to HRT. Restricting HRT use to
      women aged less than 65 years, ceasing HRT prescribing after 10 years or limiting
      combined oestrogen and progesterone HRT to five years (but otherwise keeping
      prescription levels to 2001 levels) may reduce the annual breast cancer caseload
      by 280 (2.4%), 555 (4.7%) or 674 (5.7%), respectively. In conclusion, this study
      has demonstrated that when HRT prevalence is relatively high, the effect on
      breast cancer incidence in the population will be significant. A small
      modification in HRT prescribing practices may impact breast cancer incidence in
      Australia with associated financial and health care provision implications.

PMID- 16087331
TI  - A theoretical expression for drying time of thin lumber.
AB  - An analytical expression for the drying time of thin lumber is derived, based on
      a method presented in this study. The laws of moisture content change in wood as
      function of mass transfer are used for the theoretical approach. The diffusion
      equation for moisture content is set up for a three-dimensional block of lumber
      based on the assumption of uniform initial distribution of moisture throughout
      the specimen. The boundary condition stipulates that the moisture gradient at the
      boundary is proportional to the deviation of the moisture content of the slab
      from the equilibrium value at that temperature. These conditions are used to
      derive an analytical expression for the time required to get from an initial
      moisture distribution to a desired final moisture content of thin lumber. For a
      sample calculation, the result of drying time agrees within 10% with the
      prediction of previously published analytical formulas for the drying curve.

PMID- 16087332
TI  - Hepatitis C virus NS3-4A serine protease inhibitors: SAR of P'2 moiety with
      improved potency.
AB  - We have discovered that introduction of appropriate amino acid derivatives at P'2
      position improved the binding potency of P3-capped alpha-ketoamide inhibitors of
      HCV NS3 serine protease. X-ray crystal structure of one of the inhibitors (43)
      bound to the protease revealed the importance of the P'2 moiety.

PMID- 16087333
TI  - 8-Substituted 3,4-dihydroquinolinones as a novel scaffold for atypical
      antipsychotic activity.
AB  - Several new, potent dopamine subtype 2 (DA D(2)) active compounds with serotonin
      subtype 2A (5-HT(2A)) pharmacology are presented. 8-Substituted 3,4
      dihydroquinolinones, tetrahydroquinolines, and N-acyl tetrahydroquinolines were
      evaluated in primary assays. Subtle changes on this novel scaffold translated to
      large changes in potency and selectivity in vitro. These compounds show promise
      as novel atypical antipsychotics for the treatment of schizophrenia.

PMID- 16087334
TI  - Novel inhibitors of the hepatitis C virus NS3 proteinase.
AB  - The hepatitis C virus proteinase inhibitor 4-methyl-1-(phenylmethyl)-2,6
      pyridinedione 1 undergoes a novel autoxidation process, on silica gel, leading to
      the dimer 2 as the major product, a relatively more potent inhibitor of the
      enzyme.

PMID- 16087335
TI  - An efficient synthesis of aryloxyphenyl cyclopropyl methanones: a new class of
      anti-mycobacterial agents.
AB  - An efficient, high yield and one-pot synthesis of phenyl cyclopropyl methanones
      by reaction of different aryl alcohols with 4'-fluoro-4-chloro-butyrophenone in
      THF/DMF in the presence of NaH/TBAB is reported. Most of the methanones were
      further reduced to respective alcohols or methylenes. All the compounds were
      evaluated for their anti-tubercular activities against M. tuberculosis H37Rv in
      vitro displaying MICs ranging from 25 to 3.125 microg/mL. The most active
      compounds showed activity against MDR strains and two of them (14 and 16) showed
      marginal enhancement of MST in mice.

PMID- 16087336
TI  - Hydroxylated N-alkyl-4-piperidinyl-2,3-diarylpyrrole derivatives as potent broad
      spectrum anticoccidial agents.
AB  - Diaryl-(4-piperidinyl)-pyrrole derivatives bearing hydroxylated N-alkyl
      substituents have been synthesized and evaluated as anticoccidial agents. High
      potency in Et-PKG inhibition and broad-spectrum anticoccidial activities have
      been observed on compounds, such as 4b and 5h, which are fully efficacious in
      vivo at 50 ppm in feed.

PMID- 16087337
TI  - Synthesis and antibacterial activity of a novel series of DNA gyrase inhibitors:
      5-[(E)-2-arylvinyl]pyrazoles.
AB  - The 2-arylvinyl moiety in 1-(3-chlorophenyl)-3-(4-piperidyl)-5-[(E)-2-(5-chloro
      1H-indol-3-yl)vinyl]pyrazole 2, which has previously shown improved DNA gyrase
      inhibition and target-related antibacterial activity, was transformed to other
      groups and the in vitro antibacterial activity of the synthesized compounds was
      evaluated. Many of the 5-[(E)-2-arylvinyl]pyrazoles synthesized in this study
      exhibited potent antibacterial activity against quinolone-resistant clinical
      isolates of gram-positive bacteria with minimal inhibitory concentration values
      equivalent to those against susceptible strains.

PMID- 16087338
TI  - Off limits--integrins holding boundaries in somitogenesis.
AB  - Borders are essential for demarcating repeated structures such as somites during
      vertebrate development. Two recent articles describe roles for Integrinalpha5 and
      its ligand Fibronectin1 in zebrafish anterior intersomitic boundary formation and
      link them to Notch and Eph-Ephrin pathways in epithelialization of somite
      boundary cells. Together with these pathways, Integrinalpha5 and Fibronectin1
      orchestrate the orderly formation of somite and later myotome borders. These
      studies shed light on components downstream of the periodic segmentation
      mechanism - the 'segmentation clock' - in somitogenesis.

PMID- 16087339
TI  - Microbial lithification in marine stromatolites and hypersaline mats.
AB  - Lithification in microbial ecosystems occurs when precipitation of minerals
      outweighs dissolution. Although the formation of various minerals can result from
      microbial metabolism, carbonate precipitation is possibly the most important
      process that impacts global carbon cycling. Recent investigations have produced
      models for stromatolite formation in open marine environments and lithification
      in shallow hypersaline lakes, which could be highly relevant for interpreting the
      rock record and searching for extraterrestrial life. Two factors that are
      controlled by microbial processes and physicochemical characteristics determine
      precipitation: exopolymeric substances and the saturation index, the latter being
      determined by the pH, {Ca(2+)} and {CO(3)(2-)}. Here, we evaluate community
      metabolism in microbial mats and hypothesize why these organosedimentary biofilms
      sometimes lithify and sometimes do not.

PMID- 16087340
TI  - Synthesis and initial PET imaging of new potential dopamine D3 receptor
      radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl
      cinnamoylamides.
AB  - D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin
      1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2
      [11C]MMC, [11C]1c) were synthesized for evaluation as novel potential positron
      emission tomography (PET) imaging agents for brain D3 receptors. The new tracers
      4,3,2-[11C]MMCs were prepared by O-[11C]methylation of corresponding precursors
      (E)-4,3,2-hydroxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides
      (4,3,2-HMCs) using [11C]methyl triflate and isolated by the solid-phase
      extraction (SPE) purification procedure with 40-65% radiochemical yields, decay
      corrected to end of bombardment (EOB), and a synthesis time of 15-20 min. The PET
      dynamic studies of the tracers [11C]1a-c in rats were performed using an animal
      PET scanner, IndyPET-II, developed in our laboratory. The results show that the
      brain uptake sequence was 4-[11C]MMC > 3-[11C]MMC > 2-[11C]MMC, which is
      consistent with their in vitro biological properties. The initial PET blocking
      studies of the tracers 4,3,2-[11C]MMCs with corresponding pretreatment drugs (E)
      4,3,2-methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4,3,2
      MMCs, 1a-c) had no effect on 4,3,2-[11C]MMCs-PET rat brain imaging. These results
      suggest that the localization of 4,3,2-[11C]MMCs in rat brain is mediated by
      nonspecific processes, and the visualization of 4,3,2-[11C]MMCs-PET in rat brain
      is related to nonspecific binding.

PMID- 16087341
TI  - 1-Substituted pyrazolo[1,5-c]quinazolines as novel Gly/NMDA receptor antagonists:
      synthesis, biological evaluation, and molecular modeling study.
AB  - A new set of 5,6-dihydro-pyrazolo[1,5-c]quinazoline-2-carboxylates (2-18),
      bearing different substituents (COOEt, Cl, Br, CH(3), and COOH) at position-1,
      were synthesized in order to investigate the influence of various groups at this
      specific position on Gly/NMDA receptor affinity and/or selectivity. All the
      herein reported compounds were evaluated for their binding at the Gly/NMDA, AMPA,
      and KA receptors. Some selected compounds were also tested for their functional
      antagonistic activity at both the AMPA and NMDA receptor-ion channels. The
      results obtained in this study have highlighted that a C-1 lipophilic substituent
      on the pyrazolo[1,5-c]quinazoline-2-carboxylate core shifts selectivity toward
      the Gly/NMDA receptor, while a C-1 anionic carboxylate residue is able to
      increase affinity toward this receptor subtype. In particular, the 2-carboxylic
      acids 15 and 16, bearing a chlorine atom at position-1, are not only potent
      (K(i)=0.18 and 0.16muM, respectively), but also highly Gly/NMDA versus AMPA
      selective (selectivity ratio>500). Furthermore, the 1,2-dicarboxylic acids 13 and
      14 are endowed with the highest Gly/NMDA receptor binding activity (K(i)=0.09 and
      0.059muM, respectively), among the pyrazoloquinazoline series of derivatives. A
      molecular modeling study has been carried out to better understand receptor
      affinity and selectivity of these new pyrazoloquinazoline derivatives.

PMID- 16087342
TI  - Influence of esterification and modification of A-ring in a group of lupane acids
      on their cytotoxicity.
AB  - The aim of this work was to find an optimal ester group for preparation of lupane
      derivatives connecting high cytotoxicity with good chemical and pharmacological
      properties. Activities of methyl-, pivaloyloxymethyl- (Pom-), and acetoxymethyl-
      (Acm-) esters were compared with the activity of free acids. Although the methyl-
      and Pom-esters were generally less active than free acids, some Acm-esters had
      cytotoxicity similar to or even better than the starting compounds. Cytotoxic
      activity was measured in five cancer cell lines.

PMID- 16087343
TI  - Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett
      syndrome.
AB  - Rett syndrome is an X-linked neurodevelopmental disorder caused by mutations in
      the gene encoding the transcriptional repressor methyl-CpG-binding protein 2
      (MeCP2). Here we demonstrate that the Mecp2-null mouse model of Rett syndrome
      shows an age-dependent impairment in hippocampal CA1 long-term potentiation
      induced by tetanic or theta-burst stimulation. Long-term depression induced by
      repetitive low-frequency stimulation is also absent in behaviorally symptomatic
      Mecp2-null mice. Immunoblot analyses from behaviorally symptomatic Mecp2-null
      mice reveal altered expression of N-methyl-d-aspartate receptor subunits NR2A and
      NR2B. Presynaptic function is also affected, as demonstrated by a significant
      reduction in paired-pulse facilitation. Interestingly, the properties of basal
      neurotransmission are normal in the Mecp2-null mice, consistent with our
      observations that the levels of expression of synaptic and cytoskeletal proteins,
      including glutamate receptor subunits GluR1 and GluR2, PSD95, synaptophysin-1,
      synaptobrevin-2, synaptotagmin-1, MAP2, betaIII-tubulin and NF200, are not
      significantly altered. Together, these data provide the first evidence that the
      loss of Mecp2 expression is accompanied by age-dependent alterations in
      excitatory synaptic plasticity that are likely to contribute to the cognitive and
      functional deficits underlying Rett syndrome.

PMID- 16087344
TI  - Expressions of rice sucrose non-fermenting-1 related protein kinase 1 genes are
      differently regulated during the caryopsis development.
AB  - The rice sucrose non-fermenting-1 related protein kinase 1 (SnRK1) family
      consists of three genes, which were named OSK1, OSK24 and OSK35. In order to
      elucidate the distinct functions of OSK genes, we identified precise regions for
      their expression by the promoter: GUS expression analyses as well as in situ mRNA
      localization experiments. At first, we isolated genomic clones corresponding to
      each member of OSKs in order to obtain the promoter sequences. All OSK genes
      house 11 exons and 10 introns and the positions of introns within the coding
      regions are fully conserved in all these genes. Histochemical analyses using OSK
      promoter: beta-glucronidase (OSKP:GUS) reporter genes showed that expression
      patterns of OSK1P:GUS and OSK24P:GUS were quite different in the developing
      caryopsis. The expression of OSK1P:GUS was nearly restricted in the vascular
      tissues during the caryopsis development. In contrast, the OSK24P:GUS expression
      was detected in the pericarp at the early stage with a shift to the endosperm as
      the endosperm cells were formed, and GUS staining was confined to both aleurone
      layer and endosperm cells around 15 days after flowering, when cell division of
      cellular endosperm were almost finished. The shifting pattern of the OSK24
      expression was correlated with the appearance of starch granules in each tissue.
      Similar correlation between OSK24 expression and emergence of starch granules was
      also observed at another temporal sink organ, the basal part of leaf sheath.
      These results suggest that OSK24 (rice SnRK1b) most probably have a special role
      in carbohydrate metabolism of the sink organs.

PMID- 16087345
TI  - Cyclization reactions of acylium and thioacylium ions with isocyanates and
      isothiocyanates: gas phase synthesis of 3,4-dihydro-2,4-dioxo-2H-1,3,5
      oxadiazinium ions.
AB  - Gas-phase reactions of several acylium and thioacylium ions, that is H2C=N-C+=O,
      H2C=N-C+=S, O=C=N-C+=O, S=C=N-C+=O, H3C-C+=O, and (CH3)2N-C+=O, with both a model
      isocyanate and isothiocyanate, that is, C2H5-N=C=O and C2H5-N=C=S, were
      investigated using tandem-in-space pentaquadrupole mass spectrometry. In these
      reactions, the formation of mono- and double-addition products is observed
      concurrently with proton transfer products. The double-addition products are far
      more favored in reactions with ethyl isocyanate, whereas the reactions with ethyl
      isothiocyanate form, preferentially, either the mono-addition product or proton
      transfer products, or both. Retro-addition dominates the low-energy collision
      induced dissociation of the mono- and double-addition products with reformation
      of the corresponding reactant ions. Ab initio calculations at Becke3LYP//6-311 +
      G(d,p) level indicate that cyclization is favored for the double-addition
      products and that products equivalent to those synthesized in solution, that is,
      of 3,4-dihydro-2,4-dioxo-2H-1,3,5-oxadiazinium ions and sulfur analogs, are
      formed.

PMID- 16087346
TI  - Mass spectrometric analysis of androstan-17beta-ol-3-one and androstadiene-17beta
      ol-3-one isomers.
AB  - Mass spectrometric identification and characterization of steroids using
      electrospray ionization and tandem mass spectrometry has advantages in drug
      testing and doping control analysis attributable to limitations of gas
      chromatography followed by electron ionization mass spectrometry. Steroids with
      an androstadiene-17beta-ol-3-one nucleus and double bonds located either at C-1
      and C-4, C-4 and C-9, or C-4 and C-6 were used to determine characteristic
      fragmentation pathways. Diagnostic dissociation routes are proposed using
      deuterium labeling, MS3 experiments, and analyses of structurally closely related
      compounds. Steroids such as boldenone (androst-1,4-diene-17beta-ol-3-one)
      produced characteristic product ions at m/z 121, 135, and 147. Compounds with
      double bonds at C-4 and C-9 generated abundant product ions at m/z 145 and 147.
      Conjugated double bonds at C-4 and C-6 gave rise to an intense and characteristic
      signal at m/z 133. Stereochemical differentiation between 5alpha- and 5beta
      isomers of androstan-17beta-ol-3-ones was possible because of significant
      differences in relative abundance of product ions generated by elimination of
      acetone from alpha,beta-saturated 3-keto steroids.

PMID- 16087347
TI  - Blackbody infrared radiative dissociation of nonspecific protein-carbohydrate
      complexes produced by nanoelectrospray ionization: the nature of the noncovalent
      interactions.
AB  - Gas-phase thermal dissociation experiments, implemented with blackbody infrared
      radiative dissociation (BIRD) and Fourier transform ion cyclotron resonance mass
      spectrometry, have been performed on a series of protonated and deprotonated 1:1
      and protonated 1:2 protein-carbohydrate complexes formed by nonspecific
      interactions during the nanoflow electrospray (nanoES) ionization process.
      Nonspecific interactions between the proteins bovine carbonic anhydrase II (CA),
      bovine ubiquitin (Ubq), and bovine pancreatic trypsin inhibitor and several
      carbohydrates, ranging in size from mono- to tetrasaccharides, have been
      investigated. Over the range of temperatures studied (60-190 degrees C), BIRD of
      the protonated and deprotonated complexes proceeds exclusively by the loss of the
      carbohydrate in its neutral form. The rates of dissociation of the 1:1 complexes
      containing a mono- or disaccharide decrease with reaction time, suggesting the
      presence of two or more kinetically distinct structures produced during nanoES or
      by gas-phase processes. In contrast, the 1:1 complexes of the tri- and
      tetrasaccharides exhibit simple first-order dissociation kinetics, a result that,
      on its own, is suggestive of a single preferred carbohydrate binding site or
      multiple equivalent sites in the gas phase. A comparative analysis of the
      dissociation kinetics measured for protonated 1:1 and 1:2 complexes of Ubq with
      alphaTal[alphaAbe]alphaMan further supports the presence of a single preferred
      binding site. However, a similar analysis performed on the complexes of CA and
      alphaTal[alphaAbe]alphaMan suggests that equivalent but dependent carbohydrate
      binding sites exist in the gas phase. Analysis of the Arrhenius activation
      parameters (E(a) and A) determined for the dissociation of 1:1 complexes of CA
      with structurally related trisaccharides provides evidence that neutral
      intermolecular hydrogen bonds contribute, at least in part, to the stability of
      the gaseous complexes. Surprisingly, the E(a) values for the complexes of the
      same charge state are not sensitive to the structure (primary or higher order) of
      the protein, suggesting that the carbohydrates are able to form energetically
      equivalent interactions with the various functional groups presented by the
      protein. For a given protein-carbohydrate complex, the dissociation E(a) is
      sensitive to charge state, initially increasing and then decreasing with
      increasing charge. It is proposed that both ionic and neutral hydrogen bonds
      stabilize the nonspecific protein-carbohydrate complexes in the gas phase and
      that the relative contribution of the neutral and ionic interactions is strongly
      influenced by the charge state of the complex, with neutral interactions
      dominating at low charge states and ionic interactions dominating at high charge
      states.

PMID- 16087348
TI  - In vitro assays for the determination of histone deacetylase activity.
AB  - Histone deacetylases are important regulators of transcription and an emerging
      target for anticancer drugs. We present an overview over various assay formats
      that include radiolabelled histones, oligopeptides, and small molecules as
      substrates. The advantages and disadvantages of the various formats in terms of,
      e.g., substrate availability, throughput or subtype selectivity are discussed.
      Detailed procedures for various assay types that can be used for different
      problems, such as library screening or fluorescent inhibitor testing, are given.
      We present a new protocol for a simple high-throughput assay for NAD+-dependent
      (class III) histone deacetylases, also termed sirtuins.

PMID- 16087349
TI  - Stroke burden in Mexican Americans: the impact of mortality following stroke.
AB  - PURPOSE: To estimate ethnic-specific all-cause mortality risk following ischemic
      stroke and to compare mortality risk by ethnicity. METHODS: DATA from the Brain
      Attack Surveillance in Corpus Christi Project, a population-based stroke
      surveillance study, were used. Stroke cases between January 1, 2000 and December
      31, 2002 were identified from emergency department (ED) and hospital sources (n =
      1,234). Deaths for the same period were identified from the surveillance of
      stroke cases, the Texas Department of Health, the coroner, and the Social
      Security Death Index. Ethnic-specific all-cause cumulative mortality risk was
      estimated at 28 days and 36 months using Kaplan Meier analysis. Cox proportional
      hazards regression was used to compare mortality risk by ethnicity. RESULTS:
      Cumulative 28-day all-cause mortality risk for Mexican Americans (MAs) was 7.8%
      and for non-Hispanic whites (NHWs) was 13.5%. Cumulative 36-month all-cause
      mortality risk was 31.3% in MAs and 47.2% in NHWs. MAs had lower 28-day (RR =
      0.58; 95% CI: 0.41, 0.84) and 36-month all-cause mortality risk (RR = 0.79, 95%
      CI: 0.64, 0.98) compared with NHWs, adjusted for confounders. CONCLUSIONS: Better
      survival after stroke in MAs is surprising considering their similar stroke
      subtype and severity compared with NHWs. Social or psychological factors, which
      may explain this difference, should be explored.

PMID- 16087351
TI  - Brain correlates of aesthetic judgment of beauty.
AB  - Functional MRI was used to investigate the neural correlates of aesthetic
      judgments of beauty of geometrical shapes. Participants performed evaluative
      aesthetic judgments (beautiful or not?) and descriptive symmetry judgments
      (symmetric or not?) on the same stimulus material. Symmetry was employed because
      aesthetic judgments are known to be often guided by criteria of symmetry. Novel,
      abstract graphic patterns were presented to minimize influences of attitudes or
      memory-related processes and to test effects of stimulus symmetry and complexity.
      Behavioral results confirmed the influence of stimulus symmetry and complexity on
      aesthetic judgments. Direct contrasts showed specific activations for aesthetic
      judgments in the frontomedian cortex (BA 9/10), bilateral prefrontal BA 45/47,
      and posterior cingulate, left temporal pole, and the temporoparietal junction. In
      contrast, symmetry judgments elicited specific activations in parietal and
      premotor areas subserving spatial processing. Interestingly, beautiful judgments
      enhanced BOLD signals not only in the frontomedian cortex, but also in the left
      intraparietal sulcus of the symmetry network. Moreover, stimulus complexity
      caused differential effects for each of the two judgment types. Findings indicate
      aesthetic judgments of beauty to rely on a network partially overlapping with
      that underlying evaluative judgments on social and moral cues and substantiate
      the significance of symmetry and complexity for our judgment of beauty.

PMID- 16087350
TI  - Implementation of visuospatial cues in response selection.
AB  - We used functional magnetic resonance imaging to examine neuronal activity
      reflecting the dynamic interplay of external and internal guidance of action.
      Participants performed a choice reaction time task based on spatial visual cues
      with their right and left middle and index finger. In a given trial, the cue
      either fully determined the motor response (no-selection) or indicated the number
      and location of alternative responses (selection). Compared with fully determined
      responses, the selection among (two to four) alternative responses activated a
      widespread bilateral parieto-premotor-prefrontal cortical network along with the
      cerebellum. Within this network, task-related activity patterns allowed to
      delineate two sets of brain areas. In the anterior part of rostral dorsal
      premotor cortex (PMd), the rostral cingulate and supplementary motor area and the
      right dorsolateral prefrontal cortex, the increase in activity was independent of
      spatially defined restrictions. In contrast, there was an additional increase in
      activity in the posterior part of rostral PMd, superior parietal lobule and
      parieto-occipital sulcus bilaterally as well as in the right anterior
      intraparietal sulcus, when the visuospatial cue imposed specific constraints on
      response selection. We propose that the latter set of dorsal parieto-frontal
      areas subserves rapid implementation of spatial information during visually
      guided response selection.

PMID- 16087352
TI  - Attachment-style differences in the ability to suppress negative thoughts:
      exploring the neural correlates.
AB  - Beginning in infancy, people can be characterized in terms of two dimensions of
      attachment insecurity: attachment anxiety (i.e., fear of rejection and
      abandonment) and attachment avoidance (distancing oneself from close others,
      shunning dependency; Bowlby, J., 1969/1982. Attachment and loss: Vol. 1.
      Attachment, 2nd ed., Basic Books, New York). The capacity for emotion regulation
      varies with attachment style, such that attachment-anxious individuals become
      highly emotional when threatened with social rejection or relationship loss,
      whereas avoidant individuals tend to distance themselves or disengage from
      emotional situations. In the present study, 20 women participated in an fMRI
      experiment in which they thought about--and were asked to stop thinking about-
      various relationship scenarios. When they thought about negative ones (conflict,
      breakup, death of partner), their level of attachment anxiety was positively
      correlated with activation in emotion-related areas of the brain (e.g., the
      anterior temporal pole, implicated in sadness) and inversely correlated with
      activation in a region associated with emotion regulation (orbitofrontal cortex).
      This suggests that anxious people react more strongly than non-anxious people to
      thoughts of loss while under-recruiting brain regions normally used to down
      regulate negative emotions. Participants high on avoidance failed to show as much
      deactivation as less avoidant participants in two brain regions (subcallosal
      cingulate cortex; lateral prefrontal cortex). This suggests that the avoidant
      peoples' suppression was less complete or less efficient, in line with results
      from previous behavioral experiments. These are among the first findings to
      identify some of the neural processes underlying adult attachment orientations
      and emotion regulation.

PMID- 16087353
TI  - Effects of cognitive-behavioral therapy on brain activation in specific phobia.
AB  - Little is known about the effects of successful psychotherapy on brain function
      in subjects with anxiety disorders. The present study aimed to identify changes
      in brain activation following cognitive-behavioral therapy (CBT) in subjects
      suffering from specific phobia. Using functional magnetic resonance imaging
      (fMRI), brain activation to spider videos was measured in 28 spider phobic and 14
      healthy control subjects. Phobics were randomly assigned to a therapy-group (TG)
      and a waiting-list control group (WG). Both groups of phobics were scanned twice.
      Between scanning sessions, CBT was given to the TG. Before therapy, brain
      activation did not differ between both groups of phobics. As compared to control
      subjects, phobics showed greater responses to spider vs. control videos in the
      insula and anterior cingulate cortex (ACC). CBT strongly reduced phobic symptoms
      in the TG while the WG remained behaviorally unchanged. In the second scanning
      session, a significant reduction of hyperactivity in the insula and ACC was found
      in the TG compared to the WG. These results propose that increased activation in
      the insula and ACC is associated with specific phobia, whereas an attenuation of
      these brain responses correlates with successful therapeutic intervention.

PMID- 16087354
TI  - Molecular phylogenetic analysis of nycteribiid and streblid bat flies (Diptera:
      Brachycera, Calyptratae): implications for host associations and phylogeographic
      origins.
AB  - Bat flies are a small but diverse group of highly specialized ectoparasitic,
      obligatory bloodsucking Diptera. For the first time, the phylogenetic
      relationships of 26 species and five subfamilies were investigated using four
      genes (18S rDNA, 16S rDNA, COII, and cytB) under three optimality criteria
      (maximum parsimony (MP), maximum likelihood (ML), and Bayesian inference). Tree
      topology tests of previous hypotheses were conducted under likelihood (Shimodaira
      Hasegawa test). Major findings include the non-monophyly of the Streblidae and
      the recovery of an Old World- and a New World-Clade of bat flies. These data
      ambiguously resolve basal relationships between Hippoboscidae, Glossinidae, and
      bat flies. Recovered phylogenies resulted in either monophyly (Bayesian approach)
      or paraphyly (MP/ML topologies) of the bat flies, thus obscuring the potential
      number of possible associations with bats throughout the history of this group.
      Dispersal-vicariance analysis suggested the Neotropical region as the possible
      ancestral distribution area of the New World Streblidae and the Oriental region
      for the Old World bat flies. The genes examined show conflicting support across
      the nodes of the tree, particularly in the basal positions. Additionally, there
      is poor character support among all genes for the nodes associated with early
      hippoboscoid diversification. This results in extremely short basal branches,
      adding support to the idea of a rapid radiation among the four major groups of
      Hippoboscoidea.

PMID- 16087355
TI  - Adaptation of the Folts and electrolytic methods of arterial thrombosis for the
      study of anti-thrombotic molecules in small animals.
AB  - INTRODUCTION: Animal preparations of arterial thrombosis play a crucial role in
      the discovery and validation of novel drug targets in vivo, aiding in the
      selection of new drugs for clinical evaluation. The Folts and electrolytic
      methods of arterial thrombosis are two of the most commonly used techniques to
      investigate drugs with novel anti-thrombotic potential. However, these techniques
      often involved the use of large animals such as dogs, and their application to
      small animals was limited. The aim of the present study was to adapt the Folts
      and electrolytic methods previously described in large animals to create highly
      reproducible, quantitative models of arterial thrombosis in mice, rats and
      rabbits. METHODS: Carotid artery blood flow was measured in anaesthetised mice,
      rats and rabbits. In the Folts-like method, a silk suture was tied around one
      carotid artery distal to a flow probe and tightened to cause a concentric
      stenosis sufficient to decrease blood flow by 50%. Intimal damage was induced by
      pinching the artery at the site of stenosis using forceps. The sequential
      formation and mechanical dislodgement of the resultant platelet-rich occlusive
      thrombus caused cyclic carotid artery flow reductions. In the electrolytic method
      in mice, a platinum hook electrode was placed distal to a flow probe on one
      carotid artery. The artery was clamped distally to the electrode to cause stasis
      and an electrical current (4 mA for 1.25 min) was applied before clamp release.
      This induced vascular injury resulting in occlusive thrombus (platelet- and
      fibrin-rich) formation. CONCLUSION: The Folts-like method of arterial thrombosis
      was successfully adapted for use in mice, rats and rabbits, and the electrolytic
      technique for use in mice. Compared with larger animals, these methods are highly
      reproducible and ideal for pre-clinical, cost-effective, low-cost routine
      screening of novel anti-thrombotic drugs.

PMID- 16087356
TI  - A rapid, sensitive electron-capture gas chromatographic procedure for analysis of
      metabolites of N-methyl,N-propargylphenylethylamine, a potential neuroprotective
      agent.
AB  - INTRODUCTION: N-Methyl,N-propargyphenylethylamine (MPPE) is a novel analog of (-)
      deprenyl, a drug prescribed for Parkinson's disease and shown to have
      neuroprotective and neurorescue properties in a wide variety of in vitro and in
      vivo models. MPPE is also neuroprotective, but has the advantage over (-)
      deprenyl of not being metabolized to amphetamine or N-methylamphetamine. METHOD:
      In this paper, extractive derivatization with pentafluorobenzenesulfonyl chloride
      (PFBSC) followed by electron-capture gas chromatography was utilized to study the
      metabolism of MPPE. RESULTS: The procedure is rapid and reproducible, giving
      derivatives with excellent chromatographic properties. Using this procedure, it
      has now been shown that beta-phenylethylamine (PEA), N-methylphenylethylamine (N
      methylPEA) and N-propargylphenylethylamine (N-propargylPEA) are formed from MPPE
      during incubation of this drug with human liver microsomes. Levels of all three
      metabolites were shown to increase with increasing time of incubation with the
      microsomes. DISCUSSION: Extractive derivatization with PFBSC followed by electron
      capture gas chromatography represents an efficient means of separating and
      quantitating the metabolites of MPPE, a novel neuroprotective agent.

PMID- 16087357
TI  - The efficacy and side effects of topiramate on refractory epilepsy in infants and
      young children: a multi-center clinical trial.
AB  - OBJECTIVES: This study has been conducted to assess the efficacy and safety of
      topiramate in refractory epilepsies in infants and young children. METHODS: A
      prospective clinical trial was performed in three tertiary care hospitals, on 47
      children aged 6-60 months with refractory epilepsy. Topiramate was added to at
      least two baseline anti-epileptic drugs. The efficacy was rated according to
      seizure type, frequency and duration. RESULTS: Children with refractory epilepsy
      were classified according to their clinical, neuro-imaging, and
      neurophysiological profile into infantile spasms (IS) (9 cases, 19%), Lennox
      Gastaut syndrome (LGS) (25 cases, 53%) and other epilepsies (13 cases, 28%).
      Children were also classified into cryptogenic and symptomatic epilepsy.
      Topiramate was introduced as add-on therapy in a daily dose of 1 mg/kg/day for 2
      weeks, followed by increments of 1-3 mg/kg/day at 2-week intervals, up to a
      maximum of 10 mg/kg/day. After a minimum treatment period of 6 months, 28 (60%)
      of the children had a satisfactory response (completely seizure free, or more
      than a 50% seizure reduction). The remaining 19 children (40%) had an
      unsatisfactory response (50% or less reduction in seizure frequency, no change or
      increased seizure frequency). Topiramate appeared to be equally effective in
      infantile spasms, Lennox-Gastaut syndrome and children with other types of
      epilepsy, with no significant difference between those with a satisfactory and an
      unsatisfactory response (p=0.089). There was also no significant difference in
      response between patients with cryptogenic and symptomatic epilepsy (p=0.360).
      Mild to moderate adverse effects, mainly somnolence, anorexia and nervousness,
      were present in 25 (53%) of children. One of the children developed
      hypothyroidism. CONCLUSION: Although the long term safety and possible adverse
      effects of topiramate have not been fully established in infants and young
      children, this study has shown that it is a useful option for children with
      frequent seizures unresponsive to standard anti-epileptic drugs.

PMID- 16087358
TI  - Steroids in intractable childhood epilepsy: clinical experience and review of the
      literature.
AB  - Steroids and adrenocorticotrophic hormone (ACTH) have been used for the treatment
      of infantile spasms for several years. However, the use of steroids in the
      treatment of epilepsy beyond infantile spasms has been limited to only a few
      studies. We report the experience with steroids in 32 children with intractable
      epilepsy, not including West syndrome. In 47% there was a decrease in seizure
      frequency, 25% became seizure free, 11% had a seizure reduction of >50% and 11%
      had a seizure reduction of <50%. Our study confirms the conclusions of few
      previous reports of effective adjunctive steroid treatment for children with
      intractable epilepsy. The possible side effects, however, especially during
      prolonged therapy remain an important concern.

PMID- 16087359
TI  - An audit of lamotrigine, levetiracetam and topiramate usage for epilepsy in a
      district general hospital.
AB  - The aim of this audit was to ascertain outcomes for people who had taken or who
      were still taking three "new generation" broad-spectrum antiepileptic drugs
      (AEDs), namely lamotrigine, levetiracetam and topiramate. Thirteen percent of
      people became seizure free and approximately, one-third had a reduction of
      greater than 50% in their seizures. Two-thirds of people were still taking their
      audit AED. In addition, approximately one-third of people with a learning
      disability derived substantial benefit, although the rate of seizure freedom was
      lower. All three AEDs were most successful at treating primary generalised
      epilepsy and least successful with symptomatic generalised epilepsy. With some
      reservations the data suggests that levetiracetam and topiramate are the most
      efficacious AEDs, but topiramate is the least well tolerated. These results mean
      consideration of a "general prescribing policy" is important when using and
      choosing these AEDs. We conclude that lamotrigine, levetiracetam and topiramate
      are useful additions to the armamentarium of AEDs.

PMID- 16087360
TI  - Effect of metallothionein on cell viability and its interactions with cadmium and
      zinc in HEK293 cells.
AB  - Metallothioneins (MTs) are thought to participate in a wide variety of
      physiological roles, but the mechanisms involved are still unclear. The study was
      designed to examine the possible factors related to these mechanisms. Methods,
      including transfection, MTT assay and flow cytometry, were used to investigate
      the effect of MTs on cell viability and their interactions with cadmium and zinc
      in HEK293 cells. The results showed that transient overexpression of human MT1A,
      MT2 and MT3 genes dynamically affected cell viability, and the effect was
      influenced by zinc and cadmium ions. Overexpressed MTs with added zinc showed a
      greater inhibitory effect on cell viability. Overexpressed MTs protected cells
      against low concentrations of cadmium ions (10 microM), but increased cell death
      in response to high concentrations (20-50 microM). Out of the three MTs, MT1A was
      more efficient than MT2 and MT3 in its resistance to cadmium (10 microM), and MT3
      together with zinc showed more cell growth inhibition than MT1 and MT2. These
      results indicate that both of the divalent metal ions that could bind MTs, as
      well as the individual MT isoforms, affect the role of MTs on cell viability,
      which may explain in part why the comprehensive effect of MTs on the cells was
      elusive.

PMID- 16087361
TI  - The role of inducible nitric oxide synthase in gamete interaction and
      fertilization: a comparative study on knockout mice of three NOS isoforms.
AB  - Nitric oxide (NO), which is produced from l-arginine by three isoforms of NO
      synthase (NOS), has been implicated in reproductive functions. However, the
      specific role of NOS isoforms in gamete function and fertilization is not clear.
      Three types of NOS knockout mice were super ovulated and fertilized in vitro and
      in vivo. The sperm count and motility, in vivo and in vitro fertilization rate as
      indicated by two-cell embryos and blastocyst rate were examined. The sperm count
      and motility from all three knockout mice were not significantly different from
      that of the wild type. Inducible NOS (iNOS) knockout mice were found to have the
      largest number of two-cell embryos/mouse collected after fertilization in vivo
      (P<0.01), but the rate of blastocyst formation from two-cell embryos in vitro was
      similar for all three knockouts. The rate of in vitro fertilization using either
      iNOS-deficient sperm or oocytes, but not those deficient in the other two NOS
      isoforms, was significantly elevated when compared to that in the wild type
      (P<0.001). While all three types of NOS do not seem to play a significant role in
      pre-ejaculated sperm function, iNOS may play an inhibitory role in sperm and
      oocyte functions affecting the process of fertilization and early embryo
      development.

PMID- 16087362
TI  - Effects of insulin-like growth factor-1 on okadaic acid-induced apoptosis in SH
      SY5Y cells.
AB  - The effects of insulin-like growth factor-1 (IGF-1) on the cytotoxicity and
      apoptosis induced by okadaic acid (OA) in SH-SY5Y cells were investigated. Cell
      viability was measured using the MTT (3-(4,5-dimethylthiazolyl-2)-2,-5
      diphenyltetrazolium bromide) assay. Early and late apoptosis/necrosis were
      analyzed by flow cytometry using Annexin V and propidium iodide (PI) double
      staining. Caspase-3 activation was detected by Western blot analysis.
      Preincubation with IGF-1 for 24 h prevented cytotoxicity induced by 40 nM OA
      given for 24 h, and the MTT value significantly increased. Incubation with 20 nM
      OA for 24 h caused a marked increase in the percentage of early apoptotic and
      late apoptotic/necrotic cells, which was not dependent on the activation of
      caspase-3. OA-induced apoptosis was significantly decreased by pretreatment with
      10 ng/ml of IGF-1 for 24 h. The results supported the hypothesis that IGF-1 may
      be useful in the treatment of Alzheimer's disease.

PMID- 16087363
TI  - Effect of the pancreatic digestion with liberase versus collagenase on the yield,
      function and viability of neonatal rat pancreatic islets.
AB  - Many obstacles hinder the clinical application of pancreatic islet
      transplantation as a cure for diabetes mellitus. One of them is the suitable
      isolation method of sufficient number of healthy islets for transplantation. In
      this context, liberase enzyme was developed as a purified form of the traditional
      collagenase. It was the aim of this study to investigate the effect of liberase
      digestion on the yield, function and viability of neonatal rat islets, and to
      compare the new enzyme with the collagenase. Glucose-stimulated insulin secretion
      was measured as indication of the function, insulin content as indication for the
      synthetic activity of islet cells and DNA as an indication of cell viability. The
      results showed no difference between islets isolated either with collagenase or
      liberase. Glucose stimulated similarly the insulin secretion in both. Stimulation
      index tended, without significance, to be higher (55%) in liberase-isolated
      islets compared with the collagenase islets (49%). The viability of both was
      similar. The insulin synthesis (content) tended also to be better in liberase
      isolated islets. It could be concluded that liberase could be non-significantly
      preferred in the isolation of neonatal rat islets in comparison with collagenase.

PMID- 16087364
TI  - Effect of cytokines on ICAM-1 and ZO-1 expression on human airway epithelial
      cells.
AB  - The presence of adhesion molecules on airway epithelial cells may be important in
      recruiting leukocytes to the epithelium. The study aimed at investigating the
      effects of interleukin (IL)-4, IL-8, IL-13 and interferon-gamma (IFN-gamma) on
      cell viability and intracellular adhesion molecule (ICAM)-1 and zonula occludens
      protein (ZO)-1 expression on cultured human basal and columnar airway epithelial
      cells. Cycloheximide (CHX) induced cell death in both cell lines. The cytokines
      IL-4, IL-8, IL-13 and IFN-gamma had only minor effects on cell proliferation in
      the columnar 16HBE14o-cells, and inhibited the effects of CHX on cell death. IFN
      gamma increased ICAM-1 expression in both cell lines. Western blot analysis
      showed that CHX inhibited both ICAM-1 and ZO-1 expression in the basal cell line.
      A combination of IL-4 and IFN-gamma appeared to break the tight junctions. IL-4
      and IL-13 potentiated CHX-induced apoptosis in basal cells but not in columnar
      cells, possibly due to low levels of the IL-4 receptor. It is concluded that
      cytokines produced by airway epithelium may have a role in regulating
      sequestering of leukocytes to the airways during airway inflammation.

PMID- 16087365
TI  - Induced resistance in cells exposed to repeated low doses of H2O2 involves
      enhanced activity of antioxidant enzymes.
AB  - We have derived cells from the Chinese hamster V79 cell line by conditioning them
      with repeated low doses of hydrogen peroxide (H(2)O(2)). This mimics the
      physiological condition where cells are repeatedly exposed to low levels of
      oxidants. In an attempt to characterize such cells, we have exposed both
      conditioned cells (V79(C)) and the parental V79 cells (V79(P)) to different types
      of cytotoxic agents and compared their sensitivity to cell killing. The V79(C)
      cells were found to be stably resistant to killing by agents that produced
      toxicity through oxidative stress, e.g. H(2)O(2) and cisplatin. It was also found
      that the lipid peroxidation produced by these agents were considerably lower in
      the V79(C) cells. Thus, the difference in sensitivity could be due to lesser
      extent of damage to these cells. V79(C) cells had greater antioxidant defense
      through higher GSH content and greater activity of enzymes such as Cu-Zn
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx),
      which provided protection from damage. Enzyme activities were also assayed at
      different times after treatment with various cytotoxic agents; there was a
      relatively large increase in SOD activity which perhaps plays a key role in
      determining the resistance of the V79(C) cells to killing.

PMID- 16087366
TI  - The role of the GABA(A) agonist muscimol on memory performance: reward
      contingencies determine the nature of the deficit.
AB  - A matching-to-position (MTP) paradigm was altered to influence the type of
      associations a rat would use to solve the task. Our main behavioral manipulation
      was the application of the differential outcomes procedure (DOP). The DOP
      involves correlating each to-be-remembered event with a distinct reward
      condition. This procedure results in the development of unique reward
      expectancies that enhance and guide choice behavior. Such distinct reward
      expectancies are not formed when either a common or random assignment of reward
      is used (a non-differential outcomes procedure [NOP]). Intracerebroventricular
      infusions of the amnestic agent muscimol (GABA(A) agonist) or aCSF were delivered
      to male rats trained on a delayed MTP task that implemented either the DOP or the
      NOP. Muscimol impaired performance in a dose dependent fashion in both groups-
      but the nature of the deficit differed as a function of reinforcement
      contingencies. Rats trained with the DOP displayed a non-mnemonic delay
      independent impairment: performance at all delay intervals was disrupted. In
      contrast, NOP-trained rats displayed a delay-dependent impairment demonstrating
      that muscimol can also have memory-disrupting effects. The difference in pattern
      of impairment appears to be a function of the associations formed during training
      and the type of cognitive strategies involved in maintaining behavior on a
      conditional delayed discrimination task when reinforcement contingencies are
      varied. Thus, these results demonstrate that increasing GABA(A) receptor
      activation impairs a range of associative and memory functions.

PMID- 16087367
TI  - Characterization of events preceding the release of malaria parasite from the
      host red blood cell.
AB  - The process of merozoite release involves proteolysis of both the parasitophorous
      vacuole membrane (PVM) and red blood cell membrane (RBCM), but the precise
      temporal sequence remains controversial. Using immunofluorescence microscopy and
      Western blotting of parasite-infected RBCs, we observed that the
      intraerythrocytic parasite was enclosed in a continuous ring of PVM at early
      stages of parasite development while at the segmented schizont stage, the PVM
      appeared to be integrated in the cluster of newly formed merozoites.
      Subsequently, such clusters were detected extraerythrocytically together with
      single merozoites devoid of the PVM at low frequency, suggesting a primary
      rupture of RBCM, followed by PVM rupture and release of invasive merozoites.
      Secondly, since cysteine proteases are implicated in the process of parasite
      release, antimalarial effects of 4 cysteine protease inhibitors (leupeptin, E64,
      E64d, and MDL) were tested at the late schizont stage and correlated with the
      integrity of PVM and RBCM. We observed that leupeptin and E64 treatment produced
      extraerythrocytic clusters of merozoites associated with PVM suggesting
      inhibition of PVM lysis but not RBCM lysis. Merozoites in these clusters
      developed into rings upon removal of the inhibitors. In contrast, E64d and MDL
      caused an irreversible parasite death blocking further development. Future
      characterization of the mechanism(s) of inhibition may facilitate the design of
      novel antimalarial inhibitors.

PMID- 16087368
TI  - Exosome Display technology: applications to the development of new diagnostics
      and therapeutics.
AB  - Exosome Display is a novel methodology enabling the manipulation of exosome
      protein content. This technology stems from the identification of addressing
      domains that mediate the specific distribution of proteins on exosomes. More
      particularly, Lactadherin expressed in non-mammary gland tissue has been found to
      localize to exosomes via binding of its C1C2 domain to exosome lipids. Exosome
      Display of soluble antigens and extracellular domains of membrane proteins that
      are not naturally found on exosomes occurs upon fusion of proteins with the
      Lactadherin C1C2 domain. Exosome Display of native full-length membrane proteins
      can also be achieved by non-restricted expression or sampling of membrane
      proteins on exosomes. These novel findings enable us to manipulate exosome
      composition and tailor exosomes with new desirable properties. The Exosome
      Display technology is very versatile since soluble, membrane-bound, trans
      membrane or multimeric antigens that are not naturally found on exosomes can now
      be efficiently expressed at their surface in a native conformation. The
      technology was applied to the generation of antibodies against tumor biomarkers
      such as HLA/peptide complex. This antibody method called ExoMAb can be used to
      generate antibodies against any drug target candidates, notably including G
      protein coupled receptors. The potential of Exosome Display technology for
      developing a broad range of novel diagnostics and therapeutics is discussed.

PMID- 16087369
TI  - HIV interaction with endosomes in macrophages and dendritic cells.
AB  - The human immunodeficiency virus type 1 (HIV-1) is an enveloped retrovirus that
      undergoes assembly at specific sites in infected cells. In macrophages, at least,
      this assembly occurs primarily on a subset of endocytic organelles that contain
      some of the markers found in late endosomes or multivesicular bodies (MVBs), in
      particular CD63. The budding of virus particles into endosomes has many features
      in common with the formation of exosomes and some limited biochemical comparison
      of HIV-1 particles produced from macrophages with exosomes suggests that the two
      have similar cellular origins. Here we show that macrophages infected with HIV
      contain large intracellular pools of infectious virus that can be released by
      homogenisation of intact cells. Immunoprecipitation experiments indicate this
      virus has a similar complement of cellular membrane proteins to viruses that can
      be recovered from the extracellular medium, further suggesting that viruses
      released from macrophages initially bud into endosomal organelles and are then
      released by fusion of these organelles with the plasma membrane.

PMID- 16087370
TI  - The regulation of Notch signaling in muscle stem cell activation and postnatal
      myogenesis.
AB  - The Notch signaling pathway is an evolutionarily conserved pathway that is
      critical for tissue morphogenesis during development, but is also involved in
      tissue maintenance and repair in the adult. In skeletal muscle, regulation of
      Notch signaling is involved in somitogenesis, muscle development, and the
      proliferation and cell fate determination of muscle stems cells during
      regeneration. During each of these processes, the spatial and temporal control of
      Notch signaling is essential for proper tissue formation. That control is
      mediated by a series of regulatory proteins and protein complexes that enhance or
      inhibit Notch signaling by regulating protein processing, localization, activity,
      and stability. In this review, we focus on the regulation of Notch signaling
      during postnatal muscle regeneration when muscle stem cells ("satellite cells")
      must activate, proliferate, progress along a myogenic lineage pathway, and
      ultimately differentiate to form new muscle. We review the regulators of Notch
      signaling, such as Numb and Deltex, that have documented roles in myogenesis as
      well as other regulators that may play a role in modulating Notch signaling
      during satellite cell activation and postnatal myogenesis.

PMID- 16087371
TI  - Circulating myogenic progenitors and muscle repair.
AB  - The capability of bone marrow derived cells to contribute to numerous peripheral
      tissues may hold tremendous promise for the field of regenerative medicine. In
      the context of skeletal muscle disease in particular, the ability of these cells
      to reach sites of damage through the circulation would overcome some key
      limitations of current cell therapy approaches. In muscle however, this non
      classical repair process takes place at an exceedingly low frequency and fails to
      yield any measurable functional improvement. Recent advances regarding the cell
      types or mechanisms involved in this phenomenon may now provide direction for
      strategies aimed at increasing its efficiency to therapeutic levels.

PMID- 16087372
TI  - Acute versus chronic pain treatment in Alzheimer's disease.
AB  - Several studies have suggested a lower consumption of analgesics in patients with
      Alzheimer's disease (AD) than in cognitively intact individuals (ND), but little
      attention has been paid to a distinction in analgesic consumption between acute
      and chronic pain treatment. The aim of this prospective and longitudinal study is
      a comparison in AD and ND residents at selection, and one year later, of
      analgesic consumption for acute and chronic pain, with an assessment of cognitive
      status (with the Mini Mental State Examination (MMSE)). Three hundred institution
      residents (150 AD and 150 ND), 20% male and 80% female (84.4 +/- 8.3 years old),
      were included in this study. Analgesic consumption and MMSE were reassessed at
      one year's distance (period 1 P1 and 2 (P2)). Analgesic consumption for acute
      pain was not significantly different for AD and ND at selection time or one year
      later, while MMSE declined significantly for AD (6 +/- 7 (P1) versus 4 +/- 6 (P2)
      p < 0.01, and ND individuals 23 +/- 5 (P1) versus 20 +/- 6 (P2), p < 0.01,
      respectively). Chronic pain analgesic consumption however was significantly lower
      in AD than in ND (p < 0.01). These findings may suggest a dissociation between
      sensory-discriminative (lateral pain system) and motivational-affective (medial
      pain system) aspects of pain in individuals with AD. This dissociation must be
      further investigated as it may have important consequences for pain evaluation
      and pain treatment in this vulnerable population.

PMID- 16087374
TI  - Multiple-quantum vector field imaging by magnetic resonance.
AB  - We introduce a method for non-invasively mapping fiber orientation in materials
      and biological tissues using intermolecular multiple-quantum coherences. The
      nuclear magnetic dipole field of water molecules is configured by a CRAZED
      sequence to encode spatial distributions of material heterogeneities. At any
      given point r in space, we obtain the spherical coordinates of fiber orientation
      (theta,phi) with respect to the external field by comparing three signals
      ||G(X)||, ||(Y)||, and ||G(Z)|| (modulus), acquired with linear gradients applied
      along the X, Y, and Z axes, respectively. For homogeneous isotropic materials, a
      subtraction ||G(Z)|| - ||G(X)|| - ||G(Y)|| gives zero. With anisotropic
      materials, we find an empirical relationship relating ||G(Z)|| - ||G(X)|| -
      ||G(Y)||/(||G(X)|| + ||G(Y)|| + ||G(Z)||) to the polar angle theta, while ||G(X||
      - ||G(Y)||/(||G(X)|| + ||G(Y)|| + ||G(Z)||) is related to the azimuthal angle
      phi. Experiments in structured media confirm the structural sensitivity. This
      technique can probe length scales not accessible by conventional MRI and
      diffusion tensor imaging.

PMID- 16087373
TI  - Chronic pancreatitis patients show hyperalgesia of central origin: a pilot study.
AB  - BACKGROUND: The pain of chronic pancreatitis remains challenging to manage, with
      treatment all too often being unsuccessful. A main reason for this is lacking
      understanding of underlying mechanisms of chronic pain in these patients. AIM: To
      document, using somatic quantitative sensory testing, changes in central nervous
      system processing (neuroplasticity) associated with chronic pancreatitis pain and
      thus gain insight into underlying pain mechanisms. PATIENTS AND METHODS: We
      studied 10 chronic pancreatitis patients on stable opioid analgesic medication.
      Ten matched surgical patients without pain served as controls. Pain verbal
      numeric rating scores (NRS) and thresholds to electric skin stimulation and
      pressure pain were measured in dermatomes T10 (pancreatic area), C5, T4, L1 and
      L4. RESULTS: The pancreatitis patients had a median NRS pain score of 5 (range 3
      8). Electric sensation and pain thresholds were significantly increased in the
      pancreatic region, tending to be more so in female pancreatitis patients.
      Pressure pain thresholds were significantly lower in pancreatitis patients than
      in controls, with men tending towards greater generalised relative hyperalgesia
      than women. CONCLUSIONS: Chronic pancreatitis patients show pronounced
      generalised deep hyperalgesia that is present despite opioid therapy. These
      signs, consistent with central sensitisation, appear relatively more prominent in
      men than women. There is also evidence suggesting that women may have a better
      segmental inhibitory response than men, possibly explaining their relatively less
      prominent generalised deep tissue hyperalgesia compared to men.

PMID- 16087375
TI  - Dietary protein source affects lipid metabolism in the European seabass
      (Dicentrarchus labrax).
AB  - The study was undertaken to evaluate the effects of dietary protein sources on
      lipogenesis and fat deposition in a marine teleost, the European seabass
      (Dicentrarchus labrax). Four isonitrogenous (crude protein (CP, Nx6.25), 44% DM)
      and isoenergetic (22-23 kJ/g DM) diets were formulated to contain one of the
      following as the major protein source: fish meal (FM), one of two soy protein
      concentrates (SPC) and corn gluten meal (CGM). Apparent digestibility
      coefficients of the diets and raw ingredients, as well as soluble nitrogen
      (ammonia and urea) and phosphorus excretion were measured. Growth rates of
      seabass fed plant protein-based diets were significantly lower than those fed
      fish meal based diet. The protein utilisation was strongly correlated to the
      dietary essential amino acids index. Measurements of N excretion (ammonia and
      urea nitrogen) confirmed these data. Daily fat gain at the whole body level
      ranged between 1.1 to 1.7 g/kg BW, with the highest values being recorded in fish
      fed the fish meal based diet. Levels of plasma triglycerides and cholesterol were
      lower in fish fed soy protein diets than in those fed the diet solely based on
      fish meal. Soy protein rich diets decreased the activities of selected hepatic
      lipogenic enzymes (glucose 6-phosphate dehydrogenase, malic enzyme, ATP-citrate
      lysase, acetylcoenzyme A carboxylase and fatty acid synthetase). Highest
      lipogenic enzyme activities where found in fish fed the fish meal diet, except
      for fatty acid synthetase which was increased in seabass fed the corn-gluten meal
      based diets. Overall data suggest that dietary protein sources affects fat
      deposition and the lipogenic potential in European seabass.

PMID- 16087376
TI  - Changes in muscle mRNAs for hexokinase, phosphofructokinase-1 and glycogen
      synthase in acute and persistent hypoglycemia induced by tolbutamide in chickens.
AB  - To elucidate the specificity of glucose metabolism in chicken skeletal muscle,
      changes in mRNA levels of hexokinase I (HKI), hexokinase II (HKII),
      phosphofructokinase-1 (PFK-1) and glycogen synthase (GS) were characterized in
      acute and persistent hypoglycemia induced by tolbutamide administration. In acute
      hypoglycemia, induced by a single dose of tolbutamide (100 mg/kg body mass),
      HKII, PFK-1 and GS mRNA levels remained unchanged; however, levels of HKI mRNA
      and glucose transporter 1 (GLUT1) were significantly increased 4 h after
      administration. In persistent hypoglycemia, induced by sequential administration
      of tolbutamide (100 mg/kg body mass) 3 times a day for 5 days, GS mRNA was
      significantly increased at day 5, while HKI, HKII and PFK-1 mRNA levels remained
      unchanged. These results suggest that HKI is responsible for glucose transport
      into skeletal muscle in acute hypoglycemia and that glucose preferentially enters
      the glycogenic pathway before the glycolytic pathway in persistently hypoglycemic
      chickens.

PMID- 16087377
TI  - [Impact of computed tomography (CT) and 18F-deoxyglucose-coincidence detection
      emission tomography (FDG-CDET) image fusion for optimisation of conformal
      radiotherapy in non-small-cell lung cancers].
AB  - To report a retrospective study concerning the impact of fused 18F-fluorodeoxy-D
      glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography
      (CT) images on three-dimensional conformal radiation therapy (3D-CRT) planning
      for patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One
      hundred and one patients consecutively treated for stages I-III NSCLC were
      studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in
      the same radiation treatment position. Images were coregistered using five
      fiducial markers. Target volume delineation was initially performed on the CT
      images and the corresponding FDG-PET data were subsequently used as an overlay to
      the CT data to define target volume. RESULTS: FDG-PET identified previously
      undetected distant metastatic disease in 8 patients making them ineligible for
      curative CRT (one patient presented some positive uptakes corresponding to
      concomitant pulmonary tuberculosis). Another patient was ineligible for curative
      treatment because fused CT/PET images demonstrated excessively extensive
      intrathoracic disease. The gross tumor volume (GTV) was decreased by CT/PET image
      fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV
      reduction was > or = 25% in 7 patients because CT/PET image fusion reduced
      pulmonary GTV in 6 patients (3 patients with atelectasis) and mediastinal nodal
      GTV in 1 patient. The GTV increase was > or = 25% in 14 patients due to an
      increase of the pulmonary GTV in 11 patients (4 patients with atelectasis) and
      detection of occult mediastinal lymph node involvement in 3 patients. Among 81
      patients receiving a total dose > or = 60 Gy at ICRU point, after CT/PET image
      fusion, the percentage of total lung volume receiving more than 20 Gy (VL20)
      increased in 15 cases and decreased in 22 cases. The percentage of total heart
      volume receiving more than 36 Gy increased in 8 patients and decreased in 14
      patients. The spinal cord volume receiving at least 45 Gy (2 patients) decreased.
      After multivariate analysis, one single independent factor made significant
      effect of FDG/PET on the modification of the size of the GTV: tumor with
      atelectasis (P = 0.0001). Conclusion. - Our study confirms that integrated hybrid
      PET/CT in the treatment position and coregistered images have an impact on
      treatment planning and management of patients with NSCLC. FDG images using
      dedicated PET scanners with modern image fusion techniques and respiration-gated
      acquisition protocols could improve CT/PET image coregistration. However,
      prospective studies with histological correlation are necessary and the impact on
      treatment outcome remains to be demonstrated.

PMID- 16087378
TI  - The transcription machinery and the molecular toolbox to control gene expression
      in Toxoplasma gondii and other protozoan parasites.
AB  - The phylum of Apicomplexa groups a large variety of obligate intracellular
      protozoan parasites that exhibit complicated life cycles, involving transmission
      and differentiation within and between different hosts. Little is known about the
      level of regulation and the nature of the factors controlling gene expression
      throughout their life stages. Unravelling the mechanisms that govern gene
      regulation is critical for the development of adequate tools to manipulate these
      parasites and modulate gene expression, in order to study their function in
      molecular terms in vivo. A comparative analysis of the transcriptional machinery
      of several apicomplexan genomes and other protozoan parasites has revealed the
      existence of a primitive eukaryotic transcription apparatus consisting only of a
      subset of the general transcription factors found in higher eukaryotes. These
      findings have some direct implications on development of tools.

PMID- 16087379
TI  - Amyloid arthropathy and Waldenstrom macroglobulinemia.
AB  - Amyloid arthropathy occurs chiefly as a manifestation of beta(2) microglobulin
      amyloidosis in patients receiving chronic hemodialysis. AL amyloidosis
      complicating multiple myeloma is a less common cause. Amyloid arthropathy is
      exceedingly rare in patients with Waldenstrom macroglobulinemia. We report a case
      characterized by lymphoplasmocytoid malignancy with monoclonal IgM production and
      amyloid arthropathy manifesting as bilateral symmetric polyarthritis. A synovial
      membrane biopsy established the diagnosis. Chemotherapy was effective in
      alleviating the joint manifestations. Joint symptoms in patients with monoclonal
      gammopathies, including those characterized by IgM secretion, should suggest
      amyloid arthropathy. Treatment of the blood disease may improve the joint
      symptoms.

PMID- 16087380
TI  - Endogenous sex steroids and bone mineral density in healthy men.
AB  - OBJECTIVE: To evaluate the role of endogenous sex steroids on bone mineral
      density (BMD) in healthy Turkish men. METHODS: Serum total testosterone (TT),
      free testosterone (FT), dehydroepiandrosterone sulfate and estradiol levels were
      assayed in 174 healthy men of 240 volunteers, aged 22-76 years. Dual-energy X-ray
      absorptiometry was used to measure the BMD (g/cm(2)) of lumbar spine, femoral
      neck and non-dominant proximal and distal radius-ulna sites. Linear regressions
      were conducted using each BMD site as the dependent variable and each sex steroid
      as the independent variable. Four models were run for each bone site and sex
      steroid; crude, age-adjusted, adjusted for age and body mass index (BMI), and
      adjusted for age, BMI and cigarette-smoking. RESULTS: The mean age and BMI of men
      enrolled in the study were 47.7 +/- 13.7 years and 26.9 +/- 3.6 kg/m(2). Log of
      FT was significantly associated with the BMD of distal forearm in all models
      analyzing the crude and adjusted effects. Dehydroepiandrosterone sulfate effect
      on BMD of proximal forearm came closer to the level of statistical significance
      when adjusted with age, BMI and cigarette-smoking. Estradiol and TT levels were
      not found to be associated with BMD of any sites measured. CONCLUSION: Among the
      endogenous sex steroids in men, predominantly FT seems to be one of the
      determinants of BMD. Therefore a decrease in serum levels of testosterone in
      aging male or secondary causes may negatively affect BMD.

PMID- 16087381
TI  - Cartilage breakdown in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a connective tissue disease characterized by
      destruction of the joint cartilage and subsequently of the underlying bone.
      Cartilage destruction is due to proteolysis by enzymes called metalloproteinases
      (MMPs), whose production and expression are regulated by numerous local mediators
      such as cytokines, growth factors, prostaglandins, oxygen species, and
      neuropeptides. MMP activation is largely due to a stimulatory effect of cytokines
      including IL-1beta and TNFalpha. When these cytokines bind to their membrane
      receptor, they set off signaling cascades, with activation of TGFbeta-activating
      kinase (TAK-1), of NF-kappaB by Ikappa-B kinase, of mitogen-activated protein
      kinases (MAP kinases), and finally of activator protein-1 (AP-1). Tissue
      inhibitors of MMPs (TIMPs) specifically inhibit MMPs. The interrelations between
      joint inflammation and joint destruction remain poorly understood. Experimental
      data suggest that IL-1 may be involved chiefly in joint destruction and TNF in
      joint inflammation. However, TNF antagonists are potent inhibitors of joint
      destruction in clinical practice. These results suggest that the mediators
      function as a network and that inhibition of a single mediator can affect the
      entire web. Insights gained into the innermost mechanisms of cartilage breakdown
      in patients with RA have led to major therapeutic breakthroughs. Thus, TNF
      antagonists have proved highly effective in RA. Future progress will no doubt
      stem from new knowledge about the extracellular mediators and intracellular
      signaling pathways that lead to the production and activation of enzymes
      responsible for cartilage degradation.

PMID- 16087382
TI  - Where do T cells stand in rheumatoid arthritis?
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
      destruction of cartilage and bone. The destructive lesions result from both
      immune responses and non-antigen-specific inflammatory processes. Little is known
      about the primary cause of RA. Although the primacy of T-cell-related events
      early in the disease remains debated, strong evidence indicates that autoantigen
      recognition by specific T cells is crucial to the pathophysiology of rheumatoid
      synovitis. We will discuss evolving concepts about T-cell involvement in RA and
      the roles for various T cell subsets in the development of joint abnormalities.
      The hypothesis that RA is a T-cell driven disease was put forward when studies of
      RA synovium showed numerous T cells carrying activation markers. These T cells
      were found to participate in the complex network of cell- and mediator-driven
      events leading to joint destruction. Conceivably, these T cells may be stimulated
      by an autoantigen (whether specific to the joints or ubiquitous), a highly
      conserved foreign protein cross-reacting with its human homolog, or a neo-antigen
      expressed as a result of posttranslational events. For many years, animal models
      have provided valuable evidence supporting a role for T cells in RA. We will
      review three murine models of arthritis caused by different mechanisms. In
      collagen-induced arthritis, the immune response to a joint antigen is mediated by
      pathogenic Th1 cells that elicit severe inflammatory synovitis. Spontaneous
      arthritis in K/BxN T-cell-receptor transgenic mice is related to an adaptive
      immune response against a ubiquitous protein whose end-stage effector mechanisms
      are heavily dependent on the innate immune system. In the SKG model of autoimmune
      inflammatory arthritis, a point mutation in the gene encoding a key signal
      transduction molecule in T cells causes defective T cell selection in the thymus,
      which releases polyclonal autoreactive T cells. Studies in these and other animal
      models have established that a variety of T-cell subsets whose roles vary with
      cell location and disease stage can contribute to synovitis. Finally, in addition
      to direct autoimmune attack by effector T cells, arthritis may result from
      defective homeostatic control of immunity by regulatory T cells.

PMID- 16087383
TI  - Improvements in growth parameters in children with juvenile idiopathic arthritis
      associated with the effect of methotrexate on disease activity.
AB  - OBJECTIVE: To assess changes in growth parameters associated with the response to
      methotrexate (MTX) therapy in pre-pubertal children with juvenile idiopathic
      arthritis (JIA) and who had not been treated with steroids. METHODS: We enrolled
      27 pre-pubertal children with JIA who had been treated with MTX but not with
      steroids. The children were considered to have responded to treatment if the
      number of joints with active disease decreased by at least 50% 1 year after
      treatment initiation. We compared growth parameters (height, growth rate, weight
      and body mass index (BMI)) in responders and non-responders. RESULTS: Twenty-one
      children (77.8%) responded to MTX therapy. The growth parameters were similar in
      the responders and non-responders before the onset of treatment. After 1 year,
      height (P=0.025), growth rate (P=0.03), weight (P=0.007) and BMI (P=0.05)
      increased significantly in the responder group, but not in the non-responder
      group. This increase was maintained for growth rate and weight after 2 and 3
      years of treatment. After 1 year, height (P=0.023) and growth rate (P=0.0009)
      were significantly higher in the responders than in the non-responders, and these
      differences were still significant after 3 years (P=0.01 and P=0.033,
      respectively). CONCLUSION: In pre-pubertal children with JIA, a clinical response
      to MTX therapy is associated with a significant increase in growth parameters.

PMID- 16087384
TI  - Evaluation of the e-Learning material developed by EMERALD and EMIT for
      diagnostic imaging and radiotherapy.
AB  - Two Leonardo projects, EMERALD and EMIT, have developed in a partnershipof
      university and hospital departments (the consortia) e-Learning materials in X-ray
      diagnostic radiology, nuclear medicine, radiotherapy, ultrasound and magnetic
      resonance imaging for medical physics graduates and other healthcare
      professionals. These e-Learning materials are described in a separate paper in
      this issue. To assess the effectiveness and relevance of the e-Learning material,
      a series of evaluations by student users groups plus experts in medical physics
      education and training were undertaken. The students, with backgrounds in physics
      and clinical ultrasound, reviewed the e-Learning material using an evaluation
      form developed by the consortia. The student feedback was favourable with
      students commenting that their level of knowledge had increased having completed
      the tasks. Areas identified for development were a reduction in text volume and
      an increase in the time allowed for completion of some tasks. The feedback from
      the experts was positive with an overall appreciation of the value of the
      learning material as a resource for students in medical physics field across
      Europe and identified other disciplines in which the access to the learning
      material could be useful contribution to their learning. Suggestions made for
      improvements ranged from grading the tasks into basic and advanced topics to
      increasing the interactive nature of the material. These early evaluation of the
      e-Learning material look promising and provide a framework for further
      developments in the field. Insight into users and providers views is important if
      developers are to provide relevant and worthwhile educational learning
      opportunities.

PMID- 16087385
TI  - E-learning for assistive technology professionals--a review of the TELEMATE
      project.
AB  - The Telematic Multidisciplinary Assistive Technology Education project (TELEMATE)
      was conducted during 1998-2001 by a consortium of seven European organisations
      involved in rehabilitation engineering and education. Assistive technology
      professionals work in a rapidly developing field but are few in number and widely
      dispersed, therefore, electronic delivery of their education is particularly
      advantageous. TELEMATE took existing concepts and standards in education to
      create and test an e-learning framework. As well as providing an appropriate
      learning environment, the aim was to share teaching resources and encourage a
      sound and consistent understanding of assistive technology across the European
      Union. This paper explores work carried out and the subsequent outcomes of the
      project.

PMID- 16087386
TI  - Development and evaluation of an ODL course on Medical Image Processing.
AB  - Recent developments in the field of Biomedical Engineering have led to
      considerable improvement in health care delivery, but also impose continuous
      change and improvement in education and training schemes of its professionals, in
      order to assure appropriate front-line knowledge, competencies and skills. Open
      and distance learning provides a very effective means for continuous education
      and training purposes. Image processing may be used as an attractive case for
      exploring the Collaborative Learning Model (CLM) paradigm in Open Distance
      Learning (ODL). An on-line course on Medical Image Processing, following the
      principles of collaborative learning, has been developed and evaluated. Each
      concept of the course is available in three levels of complexity. The first level
      shows only a very general description, actually the main idea. If the user is
      interested to continue, a second level is accessible, where the concept is
      explained in a more detailed manner. Moreover, for some concepts requiring
      complicated mathematical proofs, a third level is available. The course has been
      used at the European Course on Biomedical Engineering organized by the Department
      of Medical Physics, University of Patras, Greece, and was positively evaluated by
      the students.

PMID- 16087387
TI  - A case of drug-facilitated sexual assault by the use of flunitrazepam.
AB  - This article presents a case of drug-facilitated sexual assault on a female
      intoxicated with flunitrazepam. The male assailant added flunitrazepam (1 mg) to
      the female's soft drink, and had sexual intercourse with her while her
      consciousness was impaired. The complainant did not recall the events due to
      benzodiazepine-induced anterograde amnesia. The use of flunitrazepam was
      uncovered when its major metabolite, 7-amino flunitrazepam, was detected in a
      urine specimen collected when the complainant attended hospital approximately one
      day after consuming the adulterated drink.

PMID- 16087388
TI  - Skeletal muscle hypertrophy and atrophy signaling pathways.
AB  - Skeletal muscle hypertrophy is defined as an increase in muscle mass, which in
      the adult animal comes as a result of an increase in the size, as opposed to the
      number, of pre-existing skeletal muscle fibers. The protein growth factor insulin
      like growth factor 1 (IGF-1) has been demonstrated to be sufficient to induce
      skeletal muscle hypertrophy. Over the past few years, signaling pathways which
      are activated by IGF-1, and which are responsible for regulating protein
      synthesis pathways, have been defined. More recently, it has been show that IGF-1
      can also block the transcriptional upregulation of key mediators of skeletal
      muscle atrophy, the ubiquitin-ligases MuRF1 and MAFbx (also called Atrogin-1).
      Further, it has been demonstrated recently that activation of the NF-kappaB
      transcription pathway, activated by cachectic factors such as TNFalpha, is
      sufficient to induce skeletal muscle atrophy, and this atrophy occurs in part via
      NF-kappaB-mediated upregulation of MuRF1. Further work has demonstrated a trigger
      for MAFbx expression upon treatment with TNFalpha--the p38 MAPK pathway. This
      review will focus on the recent progress in the understanding of molecular
      signalling, which governs skeletal muscle atrophy and hypertrophy, and the known
      instances of cross-regulation between the two systems.

PMID- 16087389
TI  - Extracellular superoxide dismutase.
AB  - The extracellular space is protected from oxidant stress by the antioxidant
      enzyme extracellular superoxide dismutase (EC-SOD), which is highly expressed in
      selected tissues including blood vessels, heart, lungs, kidney and placenta. EC
      SOD contains a unique heparin-binding domain at its carboxy-terminus that
      establishes localization to the extracellular matrix where the enzyme scavenges
      superoxide anion. The EC-SOD heparin-binding domain can be removed by proteolytic
      cleavage, releasing active enzyme into the extracellular fluid. In addition to
      protecting against extracellular oxidative damage, EC-SOD, by scavenging
      superoxide, preserves nitric oxide bioactivity and facilitates hypoxia-induced
      gene expression. Loss of EC-SOD activity contributes to the pathogenesis of a
      number of diseases involving tissues with high levels of constitutive
      extracellular superoxide dismutase expression. A thorough understanding of the
      biological role of EC-SOD will be invaluable for developing novel therapies to
      prevent stress by extracellular oxidants.

PMID- 16087391
TI  - Nitrogen-substitution effects on the mutagenicity and cytochrome P450 isoform
      selectivity of chrysene analogs.
AB  - Nitrogen-containing analogs of chrysene, 1,10-diazachrysene (1,10-DAC) and 4,10
      DAC, were tested for mutagenicity in Salmonella typhimurium TA100 in the presence
      of rat liver S9 and human liver microsomes to investigate the effect of nitrogen
      substitution. Although these DACs could not be converted to the bay-region diol
      epoxide because of their nitrogen atoms in the bay-region epoxide or diol moiety,
      DACs were mutagenic in the Ames test with rat liver S9. Both DACs also showed
      mutagenicity in the Ames test using pooled human liver microsomes, although
      chrysene itself was not mutagenic in the presence of pooled human liver
      microsomes. The mutagenicity of DACs (50nmol/plate) in Ames tests using human
      liver microsome preparations from 10 individuals was compared with cytochrome
      P450 (CYP) activity in each microsome preparation to investigate the CYP isoform
      involved in the activation of DACs to the genotoxic forms. The numbers of induced
      revertants obtained by 1,10-DAC varied 6.2-folds (109-680) and those by 4,10-DAC
      4.8-folds (155-751) among the 10 individuals. The number of induced revertants
      obtained by 1,10-DAC significantly correlated with the CYP1A2-selective catalytic
      activity (r=0.84, P<0.01) in each microsome preparation. On the other hand, the
      number of induced revertants obtained by 4,10-DAC significantly correlated with
      the combined activity of CYP2A6 and 1A2 (CYP2A6+0.51xCYP1A2; r=0.75, P<0.01).
      However, in Ames tests using microsomes from insect cells expressing various
      human CYP isoforms, the mutagenicity of 1,10-DAC was induced only by recombinant
      human CYP1A2, whereas both recombinant human CYP2A6 and 1A2 contributed to the
      mutagenicity of 4,10-DAC. These results suggest that 1,10-DAC shows the
      mutagenicity through involvement of CYP1A2 in human liver, and 4,10-DAC does so
      through both CYP2A6 and 1A2. In conclusion, our results suggested that the
      difference in the nitrogen-substituted position in the chrysene molecule might
      affect the mutagenic activity through influencing the ratio of participation of
      the metabolic activation enzyme isoforms of CYP.

PMID- 16087392
TI  - Clinical cognition and biomedical informatics: issues of patient safety.
AB  - Recent developments in biomedical informatics research have afforded
      possibilities for great advances in health care delivery. These exciting
      opportunities also present a number of challenges to the implementation and
      integration of technologies in the workplace. As in most domains, there is a gulf
      between technologic artifacts and end users, which compromises the culture of
      safety in the workplace. Because clinical practice is a human endeavor, there is
      a need for bridging disciplines to enable clinicians to benefit from rapid
      technologic advances. This, in turn, necessitates a broadening of disciplinary
      boundaries to consider cognitive and social factors related to the design and use
      of technology. The authors argue for a place of prominence for cognitive science
      in understanding nursing factors associated with patient safety. Cognitive
      science provides a framework for the analysis and modeling of complex human
      performance. Studies of clinical cognition can meaningfully inform and shape
      design, development and assessment of information systems. Furthermore, they have
      a decisive impact on whether information technology has a positive influence on
      human performance and are especially important in understanding and promoting
      safe practices. These issues are discussed in the context of clinical informatics
      with a focus on nursing practice.

PMID- 16087393
TI  - Factors influencing early virological response in children with chronic hepatitis
      C treated with pegylated interferon and ribavirin.
AB  - Combined therapy with pegylated IFN-alpha and ribavirin enables to achieve EVR in
      8/10 treated children with CHC infected with genotype 1. Lower ALT activity,
      lower HCV viral load and small progression of fibrosis in the histopathological
      evaluation have positive influence on EVR.

PMID- 16087394
TI  - Preventive and curative role of a 43kD protein from the leaves of the herb
      Cajanus indicus L on thioacetamide-induced hepatotoxicity in vivo.
AB  - An approximately 43kD protein has been isolated and purified from the herb
      Cajanus indicus L and believed to be the most active principle for its
      hepatoprotective action. In this study, experiments have been performed to
      evaluate the effectiveness of that protein for the preventive and curative action
      against thioacetamide-induced toxicity in vivo using a murine model. Mice were
      treated with the protein intraperitoneally at a dose of 2mg/kg body weight for 2
      and 6 days before and separately 1-5 days after thioacetamide administration to
      evaluate its preventive and curative role, respectively. Thioacetamide was
      administered once at a dose of 150mg/kg body weight and after 48h of its
      application, the animals were sacrificed. Levels of various markers related to
      physiological and pathological conditions of the liver, e.g., glutamate pyruvate
      transaminase (GPT), alkaline phosphatase (ALP), etc. were determined in the
      murine sera under different experimental conditions. In addition, antioxidant
      enzymes glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase
      (CAT) as well as thiobarbituric acid reactive substances (TBARS), were measured
      from the liver homogenates. The antioxidant property of the protein was compared
      with the potent antioxidant, vitamin E (used as a positive control). The active
      principle effectively reduced the elevated GPT and ALP levels in serum and lipid
      peroxidation in the liver tissue. The reduced levels of SOD, CAT and GST by
      thioacetamide were again brought back to almost normal levels upon pre- and post
      treatment with the protein. Histopathological changes in the liver of TAA control
      and protein-treated groups also prove that the protein possesses hepatoprotective
      activity. The protein acts dose-dependently and maximum hepatoprotectivity was
      obtained when administered at a dose of 2mg/kg body weight. Data suggest that the
      active principle plays an important preventive and curative role against
      thioacetamide-induced hepatotoxicity.

PMID- 16087395
TI  - Evaluation of a Crimean-Congo hemorrhagic fever virus recombinant antigen
      expressed by Semliki Forest suicide virus for IgM and IgG antibody detection in
      human and animal sera collected in Iran.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted to humans by ticks
      or by direct contact with infected blood. It causes severe, often fatal,
      hemorrhagic diseases in humans but infection in animals is asymptomatic. CCHFV
      can spread from person to person and has caused many nosocomial outbreaks.
      Because the virus is very pathogenic for humans it must be manipulated in a
      biosafety level 4 (BSL4) laboratory, rendering the production of antigen for
      serological diagnosis difficult. To replace the native antigen, we produced a
      recombinant nucleoprotein expressed in mammalian cells via the recombinant
      Semliki Forest alphavirus replicon and developed an indirect immunofluorescence
      assay (IFA) as well as an enzyme-linked immunosorbent assay (ELISA) by
      immunocapture to detect IgM and IgG in human and animal serum. Using these
      methods, we analyzed clinical samples from human patients and sera from domestic
      animals collected in Iran and we show that this novel antigen provides a novel,
      sensitive and specific tool for CCHF diagnosis.

PMID- 16087396
TI  - Antisense approaches to immune modulation for transplant and autoimmune diseases.
AB  - Antisense oligomers have been shown to be effective tools for inhibiting gene
      expression in a highly specific manner. This technology has proven to be
      invaluable for determining gene function in conventional molecular and cellular
      studies. However, the promise of an antisense-based drug technology, suggested by
      antiviral efficacy shown nearly 25 years ago, is just now coming of age. Since
      then, numerous antisense approaches have been shown to be effective in animal
      models against numerous viruses and some tumors. Not surprisingly, antisense
      agents targeting these diseases are taking the lead in human clinical trials and
      FDA approval. Although comparatively smaller in scope, approaches for modulating
      immune responses to treat Crohn's disease, diabetes, multiple sclerosis and
      transplant rejection appear to be the next burgeoning phase of development in
      antisense therapy.

PMID- 16087397
TI  - Nucleotide analogs as novel anti-hepatitis B virus agents.
AB  - During the past decade, nucleotide analogs have emerged as novel antiviral agents
      against hepatitis B virus. Adefovir dipivoxil, a prototype phosphonate analog,
      has been approved for chronic hepatitis B virus therapy, and additional
      phosphonate analogs and di- and tri-nucleotides are under development. Several
      innovative prodrug derivatizations have also been reported to improve the oral
      bioavailability of nucleotide analogs, which usually carry a negative charge.

PMID- 16087398
TI  - Pharmacokinetics and biodistribution of phosphorodiamidate morpholino antisense
      oligomers.
AB  - The concept of using antisense oligonucleotides to interfere with gene expression
      offers a new therapeutic strategy for the treatment of diseases resulting from
      overexpression or dysfunction of certain genes. Phosphorodiamidate morpholino
      oligomers (PMOs) represent a neutral class of antisense agents that interfere
      with target gene expression either by binding and sterically blocking the
      assembly of translation machinery, resulting in inhibition of translation, or by
      altering splicing of pre-mRNA. Studies in animal models and human clinical trials
      have demonstrated a high degree of functional bioavailability in several target
      organs. Preclinical and clinical studies have shown that PMOs demonstrate
      improved efficacy, excellent kinetic behavior, biological stability, and a good
      safety profile. We conclude from the emerging data that PMOs display advantageous
      pharmaceutical properties in comparison with other antisense strategies.

PMID- 16087399
TI  - Drug-conjugated monoclonal antibodies for the treatment of cancer.
AB  - Early clinical development in the field of targeted delivery of cytotoxic drugs
      to tumors was not successful because the limitations imposed by the
      pharmacokinetic and pharmacodynamic properties of monoclonal antibodies were not
      fully appreciated. Recently, development of this concept has been reinvigorated
      by the approval of gemtuzumab ozogamicin for treatment of acute myeloid leukemia.
      Other conjugates of calicheamicin and conjugates of potent tubulin poisons
      (maytansinoids auristatins and taxoids) are undergoing clinical evaluation or are
      in preclinical development. What all of these drugs have in common is that their
      cytotoxic potencies are in the picomolar range. Thirty years after the discovery
      of monoclonal antibodies, this new generation of highly potent compounds could
      yield targeted cytotoxic agents that are effective treatments for many cancers.

PMID- 16087400
TI  - A function for the macrophage F4/80 molecule in tolerance induction.
AB  - The F4/80 monoclonal antibody has been used widely as a marker for mouse
      macrophages. The antigen (Ag) recognized by the antibody has been characterized
      as a member of the epidermal growth factor (EGF)-transmembrane 7 (TM7) family,
      although the function of the molecule has remained elusive. A recent study
      provides evidence for a role of the F4/80 molecule in the induction of
      immunological tolerance. This study appears to provide clear evidence for a role
      of the F4/80 molecule in the immune system, however, what does it really tell us
      about the activities of the F4/80 molecule?

PMID- 16087401
TI  - TNF-blocking therapies: an alternative mode of action?
AB  - Despite expanding use of drugs blocking tumour necrosis factor (TNF), their
      precise mechanisms of action remain unclear. Early assumptions that they act by
      direct neutralization of the toxic inflammatory effects of TNF might be too
      simplistic because they explain neither the range of effects observed nor the
      varying properties of different TNF-blocking agents. Recent studies have
      demonstrated a key role for mast cell-derived TNF in the increase in lymph node
      size and the organizational complexity that accompanies a developing immune
      response. Regulation of this phenomenon might comprise a novel mode of action for
      TNF-directed therapy: by preventing this lymph node hyperplasia, TNF blockade
      could modulate immune responses, ameliorating pathology in autoimmune diseases,
      such as rheumatoid arthritis.

PMID- 16087402
TI  - Imatinib: the narrow line between immune tolerance and activation.
AB  - Despite the rapid success of imatinib as a targeted cancer therapy, there seems
      to be some controversy about its influence on immune function. Research relating
      to the immunological effects of imatinib has aimed to gain insight into this
      paradoxical picture, whereby imatinib appears to be on the edge between immune
      tolerance and immune defence. In addition to the flexibility of several immune
      effectors, subtle but important experimental variations might explain the
      seemingly conflicting data, pointing to the possible use of imatinib to modulate
      immune responses against tumours. The clinical use of imatinib, and its putative
      immunomodulatory properties, represent challenging issues still to be resolved.

PMID- 16087403
TI  - Antigen sampling by mucosal dendritic cells.
AB  - The mucosal immune system is the first line of defence against bacterial and
      viral infections and is crucial in maintaining mucosal homeostasis. In the gut,
      mucosal dendritic cells offer an alternative pathway to epithelial cells for
      antigen uptake, to initiate antigen-specific immune responses. It has recently
      been shown that lamina propria dendritic cells of the small intestine actively
      sample gut bacteria through the formation of transepithelial dendrites by a
      mechanism that is dependent on the expression of the chemokine receptor CX3CR1.

PMID- 16087404
TI  - Alzheimer's disease: an intracellular movement disorder?
AB  - Axonal transport is essential for maintaining the structure and function of nerve
      cells. Deficient axonal transport has been implicated in several
      neurodegenerative diseases, including Alzheimer's disease (AD). In addition to a
      disturbed cytoskeleton and other abnormalities observed in AD that are suggestive
      of axonal transport deficits, several AD-related proteins are implicated in the
      regulation of axonal transport. A recent study has demonstrated that the axonal
      transport deficit occurs early in the course of AD, preceding amyloid pathology
      substantially in mouse models of AD; more importantly, the study showed that
      reduced axonal transport leads to increased amyloid beta production and
      deposition. These data place axonal transport deficits at a central point in the
      pathogenesis of AD.

PMID- 16087405
TI  - Transvaginal laparoscopy.
AB  - Transvaginal laparoscopy (TvL) offers an alternative to standard diagnostic
      laparoscopy in subfertile patients without obvious pelvic pathology. With a
      specially developed needle-trocar system, access to the pouch of Douglas is
      gained through a needle puncture of the posterior fornix. Performed under local
      anaesthesia or sedation with the patient in a dorsal decubitus position and using
      prewarmed Ringer lactate as a distension medium, TvL allows complete exploration
      of the tubo-ovarian structures without supplementary manipulation. The
      combination of transvaginal sonography and transvaginal endoscopy, including
      minihysteroscopy, TvL, salpingoscopy and chromopertubation test, permits the most
      complete exploration of the reproductive tract and can be used as a first-line
      investigation of female fertility in a one-stop infertility clinic. As the
      transvaginal route offers easy access to the tubes, ovaries and fossa ovarica,
      some operative procedures are possible. However, in the absence of a panoramic
      view, these will be limited to minor interventions.

PMID- 16087406
TI  - Axons mediate the distribution of arylsulfatase A within the mouse hippocampus
      upon gene delivery.
AB  - Axonal transport of the lysosomal enzyme arylsulfatase A (ARSA) may be an
      additional mechanism of enzyme distribution after in vivo brain gene transfer in
      an animal model of metachromatic leukodystrophy (MLD). Direct molecular
      demonstration of the movement of this lysosomal enzyme within axonal networks was
      missing. We generated lentiviral vectors carrying the ARSA cDNA tagged with
      hemagglutinin or the green fluorescent protein and examined the subcellular
      localization and anatomical distribution of the tagged enzymes within the MLD
      hippocampus after in vivo lentiviral gene transfer. The use of tagged ARSA
      allowed direct real-time observation and tracking of axon-dendritic transport of
      the enzyme after lentiviral gene therapy. Tagged ARSA was expressed in transduced
      pyramidal, granule, and hilar neurons within the lentiviral-injected side and was
      robustly contained in vesicles within ipsilateral axon-dendritic processes as
      well as in vesicles associated with contralateral axons and commissural axons of
      the ventral hippocampal commissure. Axonal transport of tagged ARSA led to the
      correction of hippocampal defects in long-term treated MLD mice, which was
      accompanied by enzyme uptake in nontransduced contralateral neurons, enzyme
      accumulation within the lysosomal compartment, and clearance of sulfatide storage
      deposits in this region of the MLD brain. These results contribute to the
      understanding of the mechanisms of distribution of lysosomal enzymes within the
      mammalian brain after direct gene therapy, demonstrating the use of neural
      processes for enzyme transport.

PMID- 16087407
TI  - A structured, nurse-led intervention program improves quality of life in patients
      with epilepsy: a randomized, controlled trial.
AB  - We tested the hypothesis that structured epilepsy nursing improves quality of
      life (QOL). One hundred fourteen adult patients with uncontrolled epilepsy were
      randomly assigned to either an intervention group or a control group. The
      intervention group was offered an interactive, 1-day group education program
      followed by extended nurse follow-up and counseling. The nurse was present at as
      many outpatient consultations as possible and performed repeated consultations by
      telephone. All patients completed the QOLIE-89 before randomization and after 2
      years. QOL was significantly improved from inclusion to completion of study in
      the intervention group (P=0.019), mainly in the subitems for Health
      Discouragement (P=0.01), Medication Effects (P=0.035), and Physical Role
      Limitations (P=0.05). To our knowledge, this is the first study to demonstrate a
      significant effect of a structured nurse-led intervention program in QOL of
      patients with epilepsy.

PMID- 16087408
TI  - A comparison of simultaneously recorded muscle and skin vasoconstrictor
      population activities in the rat using frequency domain analysis.
AB  - In anaesthetized rats, an apparently autonomous sympathetic rhythm (T-rhythm,
      frequency range 0.4-1.2 Hz), has been observed in nerve activity controlling
      thermoregulatory circulations but not renal nerves. To further explore the
      differential control of sympathetic activity here, we investigate whether the so
      called T-rhythm is a feature of muscle vasoconstrictor (MVC) population activity.
      Population activity was studied in vagotomised anaesthetised rats (alpha
      chloralose or urethane maintenance, after barbiturate or halothane induction,
      respectively). Some rats were additionally sino-aortic denervated (SAD) and/or
      given a pneumothorax and neuromuscular blocked. Animals were held in central
      (hypocapnic) apnoea (ventilated at 2 Hz, tidal volume<or=2 ml) so that the T
      rhythm could be studied without the confounding influence of central respiratory
      drive. In all animals (34; 17 with SAD) a peak in autospectra at T-rhythm
      frequency (T-peak: approximately 0.75 Hz) was a characteristic feature of
      activity supplying a thermoregulatory circulation (hind foot cutaneous
      vasoconstrictor activity, CVC), but not of simultaneously recorded MVC
      (gastrocnemius) activity. Percentage power at T-peak frequency was 4-5 times
      greater in CVC than MVC autospectra and at heart rate frequency approximately 14
      fold greater in MVC than CVC autospectra: no peak was present at heart rate
      frequency in CVC autospectra. No peaks were present in MVC autospectra in SAD
      preparations. MVC-CVC coherence at both frequencies was low (approximately 0.2)
      in all types of preparation; i.e., most of the activity recorded from the two
      nerves was not linearly related. We conclude that under the experimental
      conditions of this study the T-rhythm is not a robust feature of MVC activity and
      SAD does not increase MVC-CVC coherence: observations which are consistent with
      fundamentally different neural substrates regulating MVC and CVC activities under
      the conditions of these experiments.

PMID- 16087411
TI  - Quantitation of astragaloside IV in rat plasma by liquid chromatography-tandem
      mass spectrometry.
AB  - A simple, sensitive and specific liquid chromatography-tandem mass spectrometry
      method (LC-MS-MS) had been developed and validated for the quantitation of
      astragaloside IV (AGS-IV)-an active constituent of Radix Astragali in rat plasma.
      Assay method was developed by a series of operations described as below. The
      plasma proteins were precipitated with acetonitrile and digoxin was used as the
      internal standard (I.S.). The sample solution containing astragaloside IV and the
      I.S. were obtained and subsequently injected into a LC-MS-MS system following by
      a gradient elution at a slow flow rate combined with a valve diversion during the
      liquid chromatography. Chromatographic separation was achieved on a C4 (2.1 mmx10
      mm) column with a gradient mobile phase comprised of 90% methanol in water and 10
      mM ammonium acetate buffer. The analytes were detected with a PE Sciex API 3000
      mass spectrometer using turbo ion spray with positive ionization. Ions monitored
      in the multiple reaction-monitoring (MRM) modes were m/z 785.5 (precursor ion) to
      m/z 143.2 (product ion) for AGS-IV and m/z 781.2 (precursor ion) to m/z 243.3
      (product ion) for digoxin (I.S.). The method was validated over a linear range of
      1-1000 ng/ml. The low limit of quantitation was 1.0 ng/ml. Results from a 3-day
      validation study demonstrated that the developed method possessed good precision
      (CV% values were between 5.9 and 7.6%) and accuracy (96.5-102.1%) across the
      calibration range. The recoveries were 91 and 90% for astragaloside IV and I.S.,
      and no significant matrix effects were observed. QC samples were stable when kept
      at room temperature for 4 h, at -20 degrees C for 4 weeks, and after three
      freeze/thaw cycles.

PMID- 16087409
TI  - Involvement of oxidative stress response genes in redox homeostasis, the level of
      reactive oxygen species, and ageing in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae mutants lacking oxidative stress response genes were
      used to investigate which genes are required under normal aerobic conditions to
      maintain cellular redox homeostasis, using intracellular glutathione redox
      potential (glutathione E(h)) to indicate the redox environment of the cells.
      Levels of reactive oxygen species (ROS) and mitochondrial membrane potentials
      (MMP) were also assessed by FACS using dihydroethidium and rhodamine 123 as
      fluorescent probes. Cells became more oxidised as strains shifted from
      exponential growth to stationary phase. During both phases the presence of
      reduced thioredoxin and the activity of glutathione reductase were important for
      redox homeostasis. Thioredoxin reductase contributed less during exponential
      phase when there was a strong requirement for active Yap1p transcription factor,
      but was critical during stationary phase. The absence of ROS detoxification
      systems, such as catalases or superoxide dismutases, had a lesser effect on
      glutathione E(h), but a more pronounced effect on ROS levels and MMP. These
      results reflect the major shift in ROS generation as cells switch from
      fermentative to respiratory metabolism and also showed that there was not a
      strong correlation between ROS production, MMP and cellular redox environment.
      Heterogeneity was detected in populations of strains with compromised anti
      oxidant defences, and as cells aged they shifted from one cell type with low ROS
      content to another with much higher intracellular ROS.

PMID- 16087412
TI  - Determination of rabeprazole and its active metabolite, rabeprazole thioether in
      human plasma by column-switching high-performance liquid chromatography and its
      application to pharmacokinetic study.
AB  - A new sensitive column-switching high-performance liquid chromatographic (HPLC)
      method with ultraviolet detection was developed for the simultaneous
      determination of rabeprazole, a proton pump inhibitor, and its active metabolite,
      rabeprazole thioether in human plasma. Rabeprazole, its thioether metabolite and
      5-methyl-2-[(4-(3-methoxypropoxy)-3-methyl pyridin-2-yl) methyl sulfinyl]-1H
      benzimidazole, as an internal standard were extracted from 1 ml of plasma using
      diethyl ether-dichloromethane (9:1, v/v) mixture and the extract was injected
      into a column I (TSK-PW precolumn, 10 microm, 35 mmx4.6mm I.D.) for clean-up and
      column II (C18 Grand ODS-80TM TS analytical column, 5 microm, 250 mmx4.6 mm I.D.)
      for separation. The peak was detected with an ultraviolet detector set at a
      wavelength of 288 nm, and the total time for chromatographic separation was
      approximately 25 min. Mean absolute recoveries were 78.0 and 88.3% for
      rabeprazole and rabeprazole thioether, respectively. Intra- and inter-day
      coefficient variations were less than 6.5 and 4.5% for rabeprazole, 3.6 and 5.3%
      for rabeprazole thioether, respectively, at the different concentration ranges.
      The validated concentration ranges of this method were 1-1000 ng/ml for
      rabeprazole and 3-500 ng/ml for rabeprazole thioether. The limits of
      quantification were 1 ng/ml for rabeprazole and 3 ng/ml for rabeprazole
      thioether. The method was suitable for therapeutic drug monitoring and was
      applied to pharmacokinetic study in human volunteers.

PMID- 16087413
TI  - Rapid screening and characterisation of antioxidants of Cosmos caudatus using
      liquid chromatography coupled with mass spectrometry.
AB  - Ulam raja (Cosmos caudatus) is used traditionally for improving blood
      circulation. In this study, it was found that ulam raja had extremely high
      antioxidant capacity of about 2,400 mg l-ascorbic acid equivalent antioxidant
      capacity (AEAC) per 100 g of fresh sample. Antioxidant peaks in extract of ulam
      raja were firstly characterized using free radical spiking test through high
      performance liquid chromatography coupled with mass spectrometry (MS). Upon
      reaction with 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free
      radicals, intensities of antioxidant peaks will be significantly reduced.
      HPLC/MS(n) was further applied to elucidate the chemical structures of
      antioxidant peaks characterized in the spiking test. More than twenty
      antioxidants were identified in ulam raja, and their chemical structures were
      proposed. The major antioxidants in ulam raja were attributed to a number of
      proanthocyanidins that existed as dimers through hexamers, quercetin glycosides,
      chlorogenic, neo-chlorogenic, crypto-chlorogenic acid and (+)-catching. High
      content of antioxidants antioxidants contained in ulam raja could be partly
      responsible for its ability to reduce oxidative stress.

PMID- 16087414
TI  - Reducing child malnutrition in Tanzania. Combined effects of income growth and
      program interventions.
AB  - Malnutrition is associated with an inadequate diet, poor health and sanitation
      services and inadequate care for young children. A combination of income growth
      and nutrition interventions are therefore suggested to adequately tackle this
      issue [Haddad, L., Alderman, H., Appleton, S., Song, L., Yohannes, Y., 2003.
      Reducing child malnutrition: how far does income growth take us? World Bank Econ.
      Rev., 17, 107-131.], yet evidence to support this claim is often not available,
      especially for African settings. This paper evaluates the joint contribution of
      income growth and nutrition interventions towards the reduction of malnutrition.
      Using a four round panel data set from northwestern Tanzania we estimate the
      determinants of a child's nutritional status, including household income and the
      presence of nutrition interventions in the community. The results show that
      better nutrition is associated with higher income, and that nutrition
      interventions have a substantial beneficial effect. Policy simulations make clear
      that if one intends to halve malnutrition rates by 2015 (the MDG objective),
      income growth will have to be complemented by large scale program interventions.

PMID- 16087416
TI  - A window on the genetics of evolution: MC1R and plumage colouration in birds.
AB  - Melanins are a ubiquitous component of plumage colouration in birds and serve a
      wide variety of functions. Although the genetic control of melanism has been
      studied in chickens and other domestic species, little was known about the
      molecular genetics of melanin distribution in wild birds until recently. Studies
      have now revealed that a single locus, the melanocortin-1 receptor (MC1R) locus,
      is responsible for melanic polymorphisms in at least three unrelated species: the
      bananaquit, the snow goose and the arctic skua. Results show that melanism was a
      derived trait and allow other evolutionary inferences about the history of
      melanism to be made. The role of MC1R in plumage patterning is surprisingly
      diverse among different species. The conserved molecular basis for the evolution
      of melanism in birds and several other vertebrates is probably related to low
      pleiotropic effects at the MC1R.

PMID- 16087417
TI  - Ravens, Corvus corax, differentiate between knowledgeable and ignorant
      competitors.
AB  - Human social behaviour is influenced by attributing mental states to others. It
      is debated whether and to what extent such skills might occur in non-human
      animals. We here test for the possibility of ravens attributing knowledge about
      the location of food to potential competitors. In our experiments, we capitalize
      on the mutually antagonistic interactions that occur in these birds between those
      individuals that store food versus those that try to pilfer these caches. Since
      ravens' pilfer success depends on memory of observed caches, we manipulated the
      view of birds at caching, thereby designing competitors who were either
      knowledgeable or ignorant of cache location and then tested the responses of both
      storers and pilferers to those competitors at recovery. We show that ravens
      modify their cache protection and pilfer tactics not simply in response to the
      immediate behaviour of competitors, but also in relation to whether or not they
      previously had the opportunity of observing caching. Our results suggest that the
      birds not only recall whom they had seen during caching, but also know that
      obstacles can obstruct the view of others and that this affects pilfering.

PMID- 16087418
TI  - The effect of host heterogeneity and parasite intragenomic interactions on
      parasite population structure.
AB  - Understanding the processes that shape the genetic structure of parasite
      populations and the functional consequences of different parasite genotypes is
      critical for our ability to predict how an infection can spread through a host
      population and for the design of effective vaccines to combat infection and
      disease. Here, we examine how the genetic structure of parasite populations
      responds to host genetic heterogeneity. We consider the well-characterized
      molecular specificity of major histocompatibility complex binding of antigenic
      peptides to derive deterministic and stochastic models. We use these models to
      ask, firstly, what conditions favour the evolution of generalist parasite
      genotypes versus specialist parasite genotypes? Secondly, can parasite genotypes
      coexist in a population? We find that intragenomic interactions between parasite
      loci encoding antigenic peptides are pivotal in determining the outcome of
      evolution. Where parasite loci interact synergistically (i.e. the recognition of
      additional antigenic peptides has a disproportionately large effect on parasite
      fitness), generalist parasite genotypes are favoured. Where parasite loci act
      multiplicatively (have independent effects on fitness) or antagonistically (have
      diminishing effects on parasite fitness), specialist parasite genotypes are
      favoured. A key finding is that polymorphism is not stable and that, with respect
      to functionally important antigenic peptides, parasite populations are dominated
      by a single genotype.

PMID- 16087419
TI  - Alternative life histories shape brain gene expression profiles in males of the
      same population.
AB  - Atlantic salmon (Salmo salar) undergo spectacular marine migrations before homing
      to spawn in natal rivers. However, males that grow fastest early in life can
      adopt an alternative 'sneaker' tactic by maturing earlier at greatly reduced size
      without leaving freshwater. While the ultimate evolutionary causes have been well
      studied, virtually nothing is known about the molecular bases of this
      developmental plasticity. We investigate the nature and extent of coordinated
      molecular changes that accompany such a fundamental transformation by comparing
      the brain transcription profiles of wild mature sneaker males to age-matched
      immature males (future large anadromous males) and immature females. Of the ca.
      3000 genes surveyed, 15% are differentially expressed in the brains of the two
      male types. These genes are involved in a wide range of processes, including
      growth, reproduction and neural plasticity. Interestingly, despite the potential
      for wide variation in gene expression profiles among individuals sampled in
      nature, consistent patterns of gene expression were found for individuals of the
      same reproductive tactic. Notably, gene expression patterns in immature males
      were different both from immature females and sneakers, indicating that delayed
      maturation and sea migration by immature males, the 'default' life cycle, may
      actually result from an active inhibition of development into a sneaker.

PMID- 16087420
TI  - The loss of anti-predator behaviour following isolation on islands.
AB  - When isolated from predators, costly and no longer functional anti-predator
      behaviour should be selected against. Predator naivete is often pronounced on
      islands, where species are found with few or no predators. However, isolation on
      islands involves other processes, such as founder effects, that might be
      responsible for naivete or reduced anti-predator behaviour. We report the first
      comparative evidence that, in macropodid marsupials, isolation on islands may
      lead to a systematic loss of 'group size effects'-a behaviour whereby individuals
      reduce anti-predator vigilance and allocate more time to foraging as group size
      increases. Moreover, insular animals forage more, and are less vigilant, than
      mainland ones. However, we found no evidence that animals on the mainland are
      'flightier' than those on islands. Remarkably, we also found no evidence that
      isolation from all predators per se is responsible for these effects. Together,
      these results demonstrate that anti-predator behaviour may indeed be lost or
      modified when animals are isolated on islands, but it is premature to assume that
      all such behaviour is affected.

PMID- 16087421
TI  - Imitation dynamics predict vaccinating behaviour.
AB  - There exists an interplay between vaccine coverage, disease prevalence and the
      vaccinating behaviour of individuals. Moreover, because of herd immunity, there
      is also a strategic interaction between individuals when they are deciding
      whether or not to vaccinate, because the probability that an individual becomes
      infected depends upon how many other individuals are vaccinated. To understand
      this potentially complex interplay, a game dynamic model is developed in which
      individuals adopt strategies according to an imitation dynamic (a learning
      process), and base vaccination decisions on disease prevalence and perceived
      risks of vaccines and disease. The model predicts that oscillations in vaccine
      uptake are more likely in populations where individuals imitate others more
      readily or where vaccinating behaviour is more sensitive to changes in disease
      prevalence. Oscillations are also more likely when the perceived risk of vaccines
      is high. The model reproduces salient features of the time evolution of vaccine
      uptake and disease prevalence during the whole-cell pertussis vaccine scare in
      England and Wales during the 1970s. This suggests that using game theoretical
      models to predict, and even manage, the population dynamics of vaccinating
      behaviour may be feasible.

PMID- 16087422
TI  - Enhanced schooling performance in lateralized fishes.
AB  - The occurrence of functional left-right cerebral asymmetries has been documented
      in a wide range of animals, suggesting that the lateralization of cognitive
      functions enjoys some kind of selective advantage over the bilateral control of
      the same functions. Here, we compared schooling performance of fishes with high
      or low degree of lateralization, which were obtained through selective breeding.
      Schools of lateralized fishes moving in a novel environment showed significantly
      more cohesion and coordination than schools of non-lateralized (NL) fishes. Pairs
      of fishes lateralized in opposite directions were as efficient as pairs of same
      laterality, suggesting that the performance of lateralized fishes derives from a
      computational advantage rather than being the consequence of a behavioural
      similarity among schoolmates. In schools composed of both lateralized and NL
      fishes, the latter were more often at the periphery of the school while
      lateralized fishes occupied the core, a position normally safer and energetically
      less expensive.

PMID- 16087423
TI  - Females solicit sneakers to improve fertilization success in the bitterling fish
      (Rhodeus sericeus).
AB  - In most species there is greater variance in reproductive fitness among males
      than females. A consequence is the evolution of alternative male mating tactics,
      including sneaking behaviour whereby males attempt to mate with females courted
      by other males, which could undermine female choice. In bitterling (Rhodeus
      sericeus), fish that lay their eggs on the gills of living freshwater mussels,
      sneaking is common and successful. Here we show that female bitterling can
      significantly improve their fertility with an increase in the number of spawning
      partners. Females perform conspicuous behaviours associated with spawning more
      frequently close to sneakers, and spawn more eggs close to high-quality sneakers.
      This is the first time that females have been shown to engage in behaviour that
      increases the probability of sneaking, and raises the possibility of a sexual
      conflict over the number and source of ejaculates during spawning in this
      species.

PMID- 16087424
TI  - The hidden cost of information in collective foraging.
AB  - Many animals nest or roost colonially. At the start of a potential foraging
      period, they may set out independently or await information from returning
      foragers. When should such individuals act independently and when should they
      wait for information? In a social insect colony, for example, information
      transfer may greatly increase a recruit's probability of finding food, and it is
      commonly assumed that this will always increase the colony's net energy gain. We
      test this assumption with a mathematical model. Energy gain by a colony is a
      function both of the probability of finding food sources and of the duration of
      their availability. A key factor is the ratio of pro-active foragers to re-active
      foragers. When leaving the nest, pro-active foragers search for food
      independently, whereas re-active foragers rely on information from successful
      foragers to find food. Under certain conditions, the optimum strategy is totally
      independent (pro-active) foraging because potentially valuable information that
      re-active foragers may gain from successful foragers is not worth waiting for.
      This counter-intuitive outcome is remarkably robust over a wide range of
      parameters. It occurs because food sources are only available for a limited
      period. Our study emphasizes the importance of time constraints and the analysis
      of dynamics, not just steady states, to understand social insect foraging.

PMID- 16087425
TI  - Geographical variation in sound production in the anemonefish Amphiprion
      akallopisos.
AB  - Because of pelagic-larval dispersal, coral-reef fishes are distributed widely
      with minimal genetic differentiation between populations. Amphiprion akallopisos,
      a clownfish that uses sound production to defend its anemone territory, has a
      wide but disjunct distribution in the Indian Ocean. We compared sounds produced
      by these fishes from populations in Madagascar and Indonesia, a distance of 6500
      km. Differentiation of agonistic calls into distinct types indicates a complexity
      not previously recorded in fishes' acoustic communication. Moreover, various
      acoustic parameters, including peak frequency, pulse duration, number of peaks
      per pulse, differed between the two populations. The geographic comparison is the
      first to demonstrate 'dialects' in a marine fish species, and these differences
      in sound parameters suggest genetic divergence between these two populations.
      These results highlight the possible approach for investigating the role of
      sounds in fish behaviour in reproductive divergence and speciation.

PMID- 16087426
TI  - The evolution of fossoriality and the adaptive role of horns in the Mylagaulidae
      (Mammalia: Rodentia).
AB  - Ceratogaulus, a member of the extinct fossorial rodent clade Mylagaulidae, is the
      only known rodent with horns and the smallest known horned mammal. The function
      of the large, dorsally projecting nasal horns on this burrowing animal has been
      the subject of wide speculation among palaeontologists; suggested uses range from
      sexual combat to burrowing. Mammals have evolved adaptations for digging
      repeatedly; horns and other cranial appendages have also evolved numerous times.
      These two adaptations co-occur in mammals extremely rarely: only two fossil
      genera (Ceratogaulus and the xenarthran Peltephilus) and no extant mammals are
      both horned and fossorial. Tracing the evolution of fossoriality in aplodontoid
      rodents (the larger clade to which Ceratogaulus belongs) reveals that
      Ceratogaulus descended from ancestors who dug by head-lifting. Whereas this
      suggests an obvious explanation for the horns of this rodent, evidence from
      functional morphology, anatomy, phylogeny and geologic context indicates that the
      horns in Ceratogaulus were used for defence, rather than digging, and evolved to
      offset increased predation costs associated with spending more time foraging
      above ground as body size increased.

PMID- 16087427
TI  - Constitutive innate immunity is a component of the pace-of-life syndrome in
      tropical birds.
AB  - We studied the relationship between one component of immune function and basal
      metabolic rate (BMR), an indicator of the 'pace-of-life syndrome', among 12
      tropical bird species and among individuals of the tropical house wren
      (Troglodytes aedon), to gain insights into functional connections between life
      history and physiology. To assess constitutive innate immunity we introduced a
      new technique in the field of ecological and evolutionary immunology that
      quantifies the bactericidal activity of whole blood. This in vitro assay utilises
      a single blood sample to provide a functional, integrated measure of constitutive
      innate immunity. We found that the bactericidal activity of whole blood varied
      considerably among species and among individuals within a species. This variation
      was not correlated with body mass or whole-organism BMR. However, among species,
      bacteria killing activity was negatively correlated with mass-adjusted BMR,
      suggesting that species with a slower pace-of-life have evolved a more robust
      constitutive innate immune capability. Among individuals of a single species, the
      house wren, bacteria killing activity was positively correlated with mass
      adjusted BMR, pointing to physiological differences in individual quality on
      which natural selection potentially could act.

PMID- 16087428
TI  - Gene essentiality and the topology of protein interaction networks.
AB  - The mechanistic bases for gene essentiality and for cell mutational resistance
      have long been disputed. The recent availability of large protein interaction
      databases has fuelled the analysis of protein interaction networks and several
      authors have proposed that gene dispensability could be strongly related to some
      topological parameters of these networks. However, many results were based on
      protein interaction data whose biases were not taken into account. In this
      article, we show that the essentiality of a gene in yeast is poorly related to
      the number of interactants (or degree) of the corresponding protein and that the
      physiological consequences of gene deletions are unrelated to several other
      properties of proteins in the interaction networks, such as the average degrees
      of their nearest neighbours, their clustering coefficients or their relative
      distances. We also found that yeast protein interaction networks lack degree
      correlation, i.e. a propensity for their vertices to associate according to their
      degrees. Gene essentiality and more generally cell resistance against mutations
      thus seem largely unrelated to many parameters of protein network topology.

PMID- 16087429
TI  - Biomass recycling and the origin of phenotype in fungal mycelia.
AB  - Fungi are one of the most important and widespread components of the biosphere,
      and are essential for the growth of over 90% of all vascular plants. Although
      they are a separate kingdom of life, we know relatively little about the origins
      of their ubiquitous existence. This reflects a wider ignorance arising from their
      status as indeterminate organisms epitomized by extreme phenotypic plasticity
      that is essential for survival in complex environments. Here we show that the
      fungal phenotype may have its origins in the defining characteristic of
      indeterminate organisms, namely their ability to recycle locally immobilized
      internal resources into a mobilized form capable of being directed to new
      internal sinks. We show that phenotype can be modelled as an emergent phenomenon
      resulting from the interplay between simple local processes governing uptake and
      remobilization of internal resources, and macroscopic processes associated with
      their transport. Observed complex growth forms are reproduced and the sensitive
      dependence of phenotype on environmental context may be understood in terms of
      nonlinearities associated with regulation of the recycling apparatus.

PMID- 16087430
TI  - Climate change causing phase transitions of walleye pollock (Theragra
      chalcogramma) recruitment dynamics.
AB  - In 1976 the North Pacific climate shifted, resulting in an average increase of
      the water temperature. In the Gulf of Alaska the climate shift was followed (i.e.
      early 1980s) by a gradual but dramatic increase in the abundance of groundfish
      species that typically prey on pre-recruitment stages of walleye pollock. In the
      present study we used a previously parameterized model to investigate the effect
      of these climate and biological changes on the recruitment dynamics of walleye
      pollock in the Gulf of Alaska. Simulations covered the 1970-2000 time frame and
      emphasized the medium-to-long temporal scale (i.e. about 5-10 years) of
      environmental variability. Results showed that during periods characterized by
      high sea surface temperature and high predation on juvenile pollock stages,
      recruitment variability and magnitude were below average, and recruitment control
      was delayed to stages older than the 0-group. Opposite dynamics (i.e. high
      abundance and variability, and early recruitment control) occurred during periods
      characterized by low temperature and predation. These results are in general
      agreement with empirical observations, and allowed us to formulate causal
      explanations for their occurrence. We interpreted the delay of recruitment
      control and the reduction of variability as an effect of increased constraint on
      the abundance of post age-0 stages, in turn imposed by high density dependence
      and predation mortality. On the other hand, low density-dependence and predation
      favoured post age-0 survival, and allowed for an unconstrained link between
      larval and recruitment abundance. Our findings demonstrate that the dominant
      mechanisms of pollock survival change over contrasting climate regimes. Such
      changes may in turn cause a phase transition of recruitment dynamics with
      profound implications for the management of the entire stock.

PMID- 16087431
TI  - Introduction: multimodal neuroimaging of brain connectivity.

PMID- 16087432
TI  - Q-ball imaging of macaque white matter architecture.
AB  - Diffusion-weighted magnetic resonance imaging holds substantial promise as a
      technique for non-invasive imaging of white matter (WM) axonal projections. For
      diffusion imaging to be capable of providing new insight into the connectional
      neuroanatomy of the human brain, it will be necessary to histologically validate
      the technique against established tracer methods such as horseradish peroxidase
      and biocytin histochemistry. The macaque monkey provides an ideal model for
      histological validation of the diffusion imaging method due to the phylogenetic
      proximity between humans and macaques, the gyrencephalic structure of the macaque
      cortex, the large body of knowledge on the neuroanatomic connectivity of the
      macaque brain and the ability to use comparable magnetic resonance acquisition
      protocols in both species. Recently, it has been shown that high angular
      resolution diffusion imaging (HARDI) can resolve multiple axon orientations
      within an individual imaging voxel in human WM. This capability promises to boost
      the accuracy of tract reconstructions from diffusion imaging. If the macaque is
      to serve as a model for histological validation of the diffusion tractography
      method, it will be necessary to show that HARDI can also resolve intravoxel
      architecture in macaque WM. The present study therefore sought to test whether
      the technique can resolve intravoxel structure in macaque WM. Using a HARDI
      method called q-ball imaging (QBI) it was possible to resolve composite
      intravoxel architecture in a number of anatomic regions. QBI resolved intravoxel
      structure in, for example, the dorsolateral convexity, the pontine decussation,
      the pulvinar and temporal subcortical WM. The paper concludes by reviewing
      remaining challenges for the diffusion tractography project.

PMID- 16087433
TI  - Validation of q-ball imaging with a diffusion fibre-crossing phantom on a
      clinical scanner.
AB  - Magnetic resonance (MR) diffusion imaging provides a valuable tool used for
      inferring structural anisotropy of brain white matter connectivity from diffusion
      tensor imaging. Recently, several high angular resolution diffusion models were
      introduced in order to overcome the inadequacy of the tensor model for describing
      fibre crossing within a single voxel. Among them, q-ball imaging (QBI), inherited
      from the q-space method, relies on a spherical Radon transform providing a direct
      relationship between the diffusion-weighted MR signal and the orientation
      distribution function (ODF). Experimental validation of these methods in a model
      system is necessary to determine the accuracy of the methods and to optimize
      them. A diffusion phantom made up of two textile rayon fibre (comparable in
      diameter to axons) bundles, crossing at 90 degrees , was designed and dedicated
      to ex vivo q-ball validation on a clinical scanner. Normalized ODFs were
      calculated inside regions of interest corresponding to monomodal and bimodal
      configurations of underlying structures. Three-dimensional renderings of ODFs
      revealed monomodal shapes for voxels containing single-fibre population and
      bimodal patterns for voxels located within the crossing area. Principal
      orientations were estimated from ODFs and were compared with a priori structural
      fibre directions, validating efficiency of QBI for depicting fibre crossing. In
      the homogeneous regions, QBI detected the fibre angle with an accuracy of 19
      degrees and in the fibre-crossing region with an accuracy of 30 degrees .

PMID- 16087434
TI  - Probabilistic anatomical connectivity derived from the microscopic persistent
      angular structure of cerebral tissue.
AB  - Recently developed methods to extract the persistent angular structure (PAS) of
      axonal fibre bundles from diffusion-weighted magnetic resonance imaging (MRI)
      data are applied to drive probabilistic fibre tracking, designed to provide
      estimates of anatomical cerebral connectivity. The behaviour of the PAS function
      in the presence of realistic data noise is modelled for a range of single and
      multiple fibre configurations. This allows probability density functions (PDFs)
      to be generated that are parametrized according to the anisotropy of individual
      fibre populations. The PDFs are incorporated in a probabilistic fibre-tracking
      method to allow the estimation of whole-brain maps of anatomical connection
      probability. These methods are applied in two exemplar experiments in the
      corticospinal tract to show that it is possible to connect the entire primary
      motor cortex (M1) when tracing from the cerebral peduncles, and that the reverse
      experiment of tracking from M1 successfully identifies high probability
      connection via the pyramidal tracts. Using the extracted PAS in probabilistic
      fibre tracking allows higher specificity and sensitivity than previously reported
      fibre tracking using diffusion-weighted MRI in the corticospinal tract.

PMID- 16087435
TI  - Relating connectional architecture to grey matter function using diffusion
      imaging.
AB  - Understanding brain function in terms of connectional architecture is a major
      goal of neuroimaging. However, direct investigation of the influence of brain
      circuitry on function has been hindered by the lack of a technique for exploring
      anatomical connectivity in the in vivo brain. Recent advances in magnetic
      resonance diffusion imaging have given scientists access to data relating to
      local white matter architecture and, for the first time, have raised the
      possibility of in vivo investigations into brain circuitry. This review
      investigates whether diffusion imaging may be used to identify regions of grey
      matter that are distinct in their connectional architecture, and whether these
      connectional differences are reflected either in local cytoarchitecture or in
      local grey matter function. Establishing a direct relationship between regional
      boundaries based on diffusion imaging and borders between regions that perform
      different functions would not only be of great significance when interpreting
      functional results, but would also provide a first step towards the validation of
      diffusion-based anatomical connectivity studies.

PMID- 16087436
TI  - Comparing functional connectivity via thresholding correlations and singular
      value decomposition.
AB  - We compare two common methods for detecting functional connectivity: thresholding
      correlations and singular value decomposition (SVD). We find that thresholding
      correlations are better at detecting focal regions of correlated voxels, whereas
      SVD is better at detecting extensive regions of correlated voxels. We apply these
      results to resting state networks in an fMRI dataset to look for connectivity in
      cortical thickness.

PMID- 16087437
TI  - Condition-dependent functional connectivity: syntax networks in bilinguals.
AB  - This paper introduces a method to study the variation of brain functional
      connectivity networks with respect to experimental conditions in fMRI data. It is
      related to the psychophysiological interaction technique introduced by Friston et
      al. and extends to networks of correlation modulation (CM networks). Extended
      networks containing several dozens of nodes are determined in which the links
      correspond to consistent correlation modulation across subjects. In addition, we
      assess inter-subject variability and determine networks in which the condition
      dependent functional interactions can be explained by a subject-dependent
      variable. We applied the technique to data from a study on syntactical production
      in bilinguals and analysed functional interactions differentially across tasks
      (word reading or sentence production) and across languages. We find an extended
      network of consistent functional interaction modulation across tasks, whereas the
      network comparing languages shows fewer links. Interestingly, there is evidence
      for a specific network in which the differences in functional interaction across
      subjects can be explained by differences in the subjects' syntactical
      proficiency. Specifically, we find that regions, including ones that have
      previously been shown to be involved in syntax and in language production, such
      as the left inferior frontal gyrus, putamen, insula, precentral gyrus, as well as
      the supplementary motor area, are more functionally linked during sentence
      production in the second, compared with the first, language in syntactically more
      proficient bilinguals than in syntactically less proficient ones. Our approach
      extends conventional activation analyses to the notion of networks, emphasizing
      functional interactions between regions independently of whether or not they are
      activated. On the one hand, it gives rise to testable hypotheses and allows an
      interpretation of the results in terms of the previous literature, and on the
      other hand, it provides a basis for studying the structure of functional
      interactions as a whole, and hence represents a further step towards the notion
      of large-scale networks in functional imaging.

PMID- 16087438
TI  - Undirected graphs of frequency-dependent functional connectivity in whole brain
      networks.
AB  - We explored properties of whole brain networks based on multivariate spectral
      analysis of human functional magnetic resonance imaging (fMRI) time-series
      measured in 90 cortical and subcortical subregions in each of five healthy
      volunteers studied in the (no-task) resting state. We note that undirected graphs
      representing conditional independence between multivariate time-series can be
      more readily approached in the frequency domain than the time domain. Estimators
      of partial coherency and normalized partial mutual information phi, an integrated
      measure of partial coherence over an arbitrary frequency band, are applied. Using
      these tools, we replicate the prior observations that bilaterally homologous
      brain regions tend to be strongly connected and functional connectivity is
      generally greater at low frequencies [0.0004, 0.1518 Hz]. We also show that long
      distance intrahemispheric connections between regions of prefrontal and parietal
      cortex were more salient at low frequencies than at frequencies greater than 0.3
      Hz, whereas many local or short-distance connections, such as those comprising
      segregated dorsal and ventral paths in posterior cortex, were also represented in
      the graph of high-frequency connectivity. We conclude that the partial coherency
      spectrum between a pair of human brain regional fMRI time-series depends on the
      anatomical distance between regions: long-distance (greater than 7 cm) edges
      represent conditional dependence between bilaterally symmetric neocortical
      regions, and between regions of prefrontal and parietal association cortex in the
      same hemisphere, are predominantly subtended by low-frequency components.

PMID- 16087439
TI  - Determination of transmission patterns in multichannel data.
AB  - The power of today's laboratory equipment allows more and more data channels to
      be easily recorded. However, some misunderstandings about processing such
      multivariate data may still be found in the literature. The typical mistake is to
      treat a multichannel system as comprising pairs of channels; this approach does
      not use all the collected information about the investigated system, and may lead
      to erroneous conclusions. In this paper, the differences between single- and
      multichannel approaches will be briefly summarized and some examples of problems
      will be described.

PMID- 16087440
TI  - A graphical approach for evaluating effective connectivity in neural systems.
AB  - The identification of effective connectivity from time-series data such as
      electroencephalogram (EEG) or time-resolved function magnetic resonance imaging
      (fMRI) recordings is an important problem in brain imaging. One commonly used
      approach to inference effective connectivity is based on vector autoregressive
      models and the concept of Granger causality. However, this probabilistic concept
      of causality can lead to spurious causalities in the presence of latent
      variables. Recently, graphical models have been used to discuss problems of
      causal inference for multivariate data. In this paper, we extend these concepts
      to the case of time-series and present a graphical approach for discussing
      Granger-causal relationships among multiple time-series. In particular, we
      propose a new graphical representation that allows the characterization of
      spurious causality and, thus, can be used to investigate spurious causality. The
      method is demonstrated with concurrent EEG and fMRI recordings which are used to
      investigate the interrelations between the alpha rhythm in the EEG and blood
      oxygenation level dependent (BOLD) responses in the fMRI. The results confirm
      previous findings on the location of the source of the EEG alpha rhythm.

PMID- 16087441
TI  - Estimating brain functional connectivity with sparse multivariate autoregression.
AB  - There is much current interest in identifying the anatomical and functional
      circuits that are the basis of the brain's computations, with hope that
      functional neuroimaging techniques will allow the in vivo study of these neural
      processes through the statistical analysis of the time-series they produce.
      Ideally, the use of techniques such as multivariate autoregressive (MAR)
      modelling should allow the identification of effective connectivity by combining
      graphical modelling methods with the concept of Granger causality. Unfortunately,
      current time-series methods perform well only for the case that the length of the
      time-series Nt is much larger than p, the number of brain sites studied, which is
      exactly the reverse of the situation in neuroimaging for which relatively short
      time-series are measured over thousands of voxels. Methods are introduced for
      dealing with this situation by using sparse MAR models. These can be estimated in
      a two-stage process involving (i) penalized regression and (ii) pruning of
      unlikely connections by means of the local false discovery rate developed by
      Efron. Extensive simulations were performed with idealized cortical networks
      having small world topologies and stable dynamics. These show that the detection
      efficiency of connections of the proposed procedure is quite high. Application of
      the method to real data was illustrated by the identification of neural circuitry
      related to emotional processing as measured by BOLD.

PMID- 16087442
TI  - Bilinear dynamical systems.
AB  - In this paper, we propose the use of bilinear dynamical systems (BDS)s for model
      based deconvolution of fMRI time-series. The importance of this work lies in
      being able to deconvolve haemodynamic time-series, in an informed way, to
      disclose the underlying neuronal activity. Being able to estimate neuronal
      responses in a particular brain region is fundamental for many models of
      functional integration and connectivity in the brain. BDSs comprise a stochastic
      bilinear neurodynamical model specified in discrete time, and a set of linear
      convolution kernels for the haemodynamics. We derive an expectation-maximization
      (EM) algorithm for parameter estimation, in which fMRI time-series are
      deconvolved in an E-step and model parameters are updated in an M-Step. We report
      preliminary results that focus on the assumed stochastic nature of the
      neurodynamic model and compare the method to Wiener deconvolution.

PMID- 16087443
TI  - Estimation of the transmission time of stimulus-locked responses: modelling and
      stochastic phase resetting analysis.
AB  - A model of two coupled phase oscillators is studied, where both oscillators are
      subject to random forces but only one oscillator is repetitively stimulated with
      a pulsatile stimulus. A pulse causes a reset, which is transmitted to the other
      oscillator via the coupling. The transmission time of the cross-trial (CT)
      averaged responses, i.e. the difference in time between the maxima of the CT
      averaged responses of both oscillators differs from the time difference between
      the maxima of the oscillators' resets. In fact, the transmission time of the CT
      averaged responses directly corresponds to the phase difference in the stable
      synchronized state with integer multiples of the oscillators' mean period added
      to it. With CT averaged responses it is impossible to reliably estimate the time
      elapsing, owing to the stimulus' action being transmitted between the two
      oscillators.

PMID- 16087444
TI  - Investigations into resting-state connectivity using independent component
      analysis.
AB  - Inferring resting-state connectivity patterns from functional magnetic resonance
      imaging (fMRI) data is a challenging task for any analytical technique. In this
      paper, we review a probabilistic independent component analysis (PICA) approach,
      optimized for the analysis of fMRI data, and discuss the role which this
      exploratory technique can take in scientific investigations into the structure of
      these effects. We apply PICA to fMRI data acquired at rest, in order to
      characterize the spatio-temporal structure of such data, and demonstrate that
      this is an effective and robust tool for the identification of low-frequency
      resting-state patterns from data acquired at various different spatial and
      temporal resolutions. We show that these networks exhibit high spatial
      consistency across subjects and closely resemble discrete cortical functional
      networks such as visual cortical areas or sensory-motor cortex.

PMID- 16087445
TI  - Brain connectivity at different time-scales measured with EEG.
AB  - We present an overview of different methods for decomposing a multichannel
      spontaneous electroencephalogram (EEG) into sets of temporal patterns and
      topographic distributions. All of the methods presented here consider the scalp
      electric field as the basic analysis entity in space. In time, the resolution of
      the methods is between milliseconds (time-domain analysis), subseconds (time- and
      frequency-domain analysis) and seconds (frequency-domain analysis). For any of
      these methods, we show that large parts of the data can be explained by a small
      number of topographic distributions. Physically, this implies that the brain
      regions that generated one of those topographies must have been active with a
      common phase. If several brain regions are producing EEG signals at the same time
      and frequency, they have a strong tendency to do this in a synchronized mode.
      This view is illustrated by several examples (including combined EEG and
      functional magnetic resonance imaging (fMRI)) and a selective review of the
      literature. The findings are discussed in terms of short-lasting binding between
      different brain regions through synchronized oscillations, which could constitute
      a mechanism to form transient, functional neurocognitive networks.

PMID- 16087446
TI  - Fusing EEG and fMRI based on a bottom-up model: inferring activation and
      effective connectivity in neural masses.
AB  - The elucidation of the complex machinery used by the human brain to segregate and
      integrate information while performing high cognitive functions is a subject of
      imminent future consequences. The most significant contributions to date in this
      field, known as cognitive neuroscience, have been achieved by using innovative
      neuroimaging techniques, such as electroencephalogram (EEG) and functional
      magnetic resonance imaging (fMRI), which measure variations in both the time and
      the space of some interpretable physical magnitudes. Extraordinary maps of
      cerebral activation involving function-restricted brain areas, as well as graphs
      of the functional connectivity between them, have been obtained from EEG and fMRI
      data by solving some spatio-temporal inverse problems, which constitutes a top
      down approach. However, in many cases, a natural bridge between these maps/graphs
      and the causal physiological processes is lacking, leading to some
      misunderstandings in their interpretation. Recent advances in the comprehension
      of the underlying physiological mechanisms associated with different cerebral
      scales have provided researchers with an excellent scenario to develop
      sophisticated biophysical models that permit an integration of these neuroimage
      modalities, which must share a common aetiology. This paper proposes a bottom-up
      approach, involving physiological parameters in a specific mesoscopic dynamic
      equations system. Further observation equations encapsulating the relationship
      between the mesostates and the EEG/fMRI data are obtained on the basis of the
      physical foundations of these techniques. A methodology for the estimation of
      parameters from fused EEG/fMRI data is also presented. In this context, the
      concepts of activation and effective connectivity are carefully revised. This new
      approach permits us to examine and discuss some future prospects for the
      integration of multimodal neuroimages.

PMID- 16087447
TI  - Multiscale brain modelling.
AB  - A central difficulty of brain modelling is to span the range of spatio-temporal
      scales from synapses to the whole brain. This paper overviews results from a
      recent model of the generation of brain electrical activity that incorporates
      both basic microscopic neurophysiology and large-scale brain anatomy to predict
      brain electrical activity at scales from a few tenths of a millimetre to the
      whole brain. This model incorporates synaptic and dendritic dynamics,
      nonlinearity of the firing response, axonal propagation and corticocortical and
      corticothalamic pathways. Its relatively few parameters measure quantities such
      as synaptic strengths, corticothalamic delays, synaptic and dendritic time
      constants, and axonal ranges, and are all constrained by independent
      physiological measurements. It reproduces quantitative forms of
      electroencephalograms seen in various states of arousal, evoked response
      potentials, coherence functions, seizure dynamics and other phenomena. Fitting
      model predictions to experimental data enables underlying physiological
      parameters to be inferred, giving a new non-invasive window into brain function
      that complements slower, but finer-resolution, techniques such as fMRI. Because
      the parameters measure physiological quantities relating to multiple scales, and
      probe deep structures such as the thalamus, this will permit the testing of a
      range of hypotheses about vigilance, cognition, drug action and brain function.
      In addition, referencing to a standardized database of subjects adds strength and
      specificity to characterizations obtained.

PMID- 16087448
TI  - Dynamics of a neural system with a multiscale architecture.
AB  - The architecture of the brain is characterized by a modular organization repeated
      across a hierarchy of spatial scales-neurons, minicolumns, cortical columns,
      functional brain regions, and so on. It is important to consider that the
      processes governing neural dynamics at any given scale are not only determined by
      the behaviour of other neural structures at that scale, but also by the emergent
      behaviour of smaller scales, and the constraining influence of activity at larger
      scales. In this paper, we introduce a theoretical framework for neural systems in
      which the dynamics are nested within a multiscale architecture. In essence, the
      dynamics at each scale are determined by a coupled ensemble of nonlinear
      oscillators, which embody the principle scale-specific neurobiological processes.
      The dynamics at larger scales are 'slaved' to the emergent behaviour of smaller
      scales through a coupling function that depends on a multiscale wavelet
      decomposition. The approach is first explicated mathematically. Numerical
      examples are then given to illustrate phenomena such as between-scale
      bifurcations, and how synchronization in small-scale structures influences the
      dynamics in larger structures in an intuitive manner that cannot be captured by
      existing modelling approaches. A framework for relating the dynamical behaviour
      of the system to measured observables is presented and further extensions to
      capture wave phenomena and mode coupling are suggested.

PMID- 16087449
TI  - Stochastic models of neuronal dynamics.
AB  - Cortical activity is the product of interactions among neuronal populations.
      Macroscopic electrophysiological phenomena are generated by these interactions.
      In principle, the mechanisms of these interactions afford constraints on
      biologically plausible models of electrophysiological responses. In other words,
      the macroscopic features of cortical activity can be modelled in terms of the
      microscopic behaviour of neurons. An evoked response potential (ERP) is the mean
      electrical potential measured from an electrode on the scalp, in response to some
      event. The purpose of this paper is to outline a population density approach to
      modelling ERPs. We propose a biologically plausible model of neuronal activity
      that enables the estimation of physiologically meaningful parameters from
      electrophysiological data. The model encompasses four basic characteristics of
      neuronal activity and organization: (i) neurons are dynamic units, (ii) driven by
      stochastic forces, (iii) organized into populations with similar biophysical
      properties and response characteristics and (iv) multiple populations interact to
      form functional networks. This leads to a formulation of population dynamics in
      terms of the Fokker-Planck equation. The solution of this equation is the
      temporal evolution of a probability density over state-space, representing the
      distribution of an ensemble of trajectories. Each trajectory corresponds to the
      changing state of a neuron. Measurements can be modelled by taking expectations
      over this density, e.g. mean membrane potential, firing rate or energy
      consumption per neuron. The key motivation behind our approach is that ERPs
      represent an average response over many neurons. This means it is sufficient to
      model the probability density over neurons, because this implicitly models their
      average state. Although the dynamics of each neuron can be highly stochastic, the
      dynamics of the density is not. This means we can use Bayesian inference and
      estimation tools that have already been established for deterministic systems.
      The potential importance of modelling density dynamics (as opposed to more
      conventional neural mass models) is that they include interactions among the
      moments of neuronal states (e.g. the mean depolarization may depend on the
      variance of synaptic currents through nonlinear mechanisms).Here, we formulate a
      population model, based on biologically informed model-neurons with spike-rate
      adaptation and synaptic dynamics. Neuronal sub-populations are coupled to form an
      observation model, with the aim of estimating and making inferences about
      coupling among sub-populations using real data. We approximate the time-dependent
      solution of the system using a bi-orthogonal set and first-order perturbation
      expansion. For didactic purposes, the model is developed first in the context of
      deterministic input, and then extended to include stochastic effects. The
      approach is demonstrated using synthetic data, where model parameters are
      identified using a Bayesian estimation scheme we have described previously.

PMID- 16087450
TI  - Investigating the neural basis for functional and effective connectivity.
      Application to fMRI.
AB  - Viewing cognitive functions as mediated by networks has begun to play a central
      role in interpreting neuroscientific data, and studies evaluating interregional
      functional and effective connectivity have become staples of the neuroimaging
      literature. The neurobiological substrates of functional and effective
      connectivity are, however, uncertain. We have constructed neurobiologically
      realistic models for visual and auditory object processing with multiple
      interconnected brain regions that perform delayed match-to-sample (DMS) tasks. We
      used these models to investigate how neurobiological parameters affect the
      interregional functional connectivity between functional magnetic resonance
      imaging (fMRI) time-series. Variability is included in the models as subject-to
      subject differences in the strengths of anatomical connections, scan-to-scan
      changes in the level of attention, and trial-to-trial interactions with non
      specific neurons processing noise stimuli. We find that time-series correlations
      between integrated synaptic activities between the anterior temporal and the
      prefrontal cortex were larger during the DMS task than during a control task.
      These results were less clear when the integrated synaptic activity was
      haemodynamically convolved to generate simulated fMRI activity. As the strength
      of the model anatomical connectivity between temporal and frontal cortex was
      weakened, so too was the strength of the corresponding functional connectivity.
      These results provide a partial validation for using fMRI functional connectivity
      to assess brain interregional relations.

PMID- 16087452
TI  - Ethnicity, genetics, and breast cancer: media portrayal of disease identities.
AB  - OBJECTIVE: To describe, compare, and analyze how the risk of breast cancer is
      framed in newspapers directed towards an ethnic minority population (Jewish) with
      higher risk of inherited breast cancer compared with newspaper coverage for the
      general population (Anglo-Canadian) without this risk. DESIGN: This investigation
      utilized a mixed methods (quantitative and qualitative) approach. The design
      emphasized a content analysis conducted on ethnically specific and non-ethnic
      newspaper articles. RESULTS: It is noteworthy that the 'Jewish' newspapers devote
      a substantially larger proportion of articles on breast cancer to genetic risk as
      the key risk factor for this disease. Articles in the Jewish newspapers tend to
      link being a Jewish woman with being at risk for a diagnosis of breast cancer.
      This ethnic 'identity' is reinforced through the repeated association of Jewish
      heritage and genetic breast cancer risk at the exclusion of other known risk
      factors. This isolated genetic link to breast cancer is not a message that is
      replicated within the provincial newsprint articles. CONCLUSIONS: These findings
      assist in the facilitation of prevention and treatment of those with or at risk
      of breast cancer. The health policy implications of this portrayal as well as
      suggestions for change are considered.

PMID- 16087451
TI  - Inferring causality in brain images: a perturbation approach.
AB  - When engaged by a stimulus, different nodes of a neural circuit respond in a
      coordinated fashion. We often ask whether there is a cause and effect in such
      interregional interactions. This paper proposes that we can infer causality in
      functional connectivity by employing a 'perturb and measure' approach. In the
      human brain, this has been achieved by combining transcranial magnetic
      stimulation (TMS) with positron emission tomography (PET), functional magnetic
      resonance imaging or electroencephalography. Here, I will illustrate this
      approach by reviewing some of our TMS/PET work, and will conclude by discussing a
      few methodological and theoretical challenges facing those studying neural
      connectivity using a perturbation.

PMID- 16087453
TI  - Accessibility and use of touchscreens by black and ethnic minority groups in the
      three cities project.
AB  - OBJECTIVES: The public are being encouraged by Government, at a national level,
      to take a greater role in the management of their health and healthcare but
      information to support this is not always accessible to black and ethnic minority
      group members who do not speak or read English. This study looks at the
      feasibility of providing health-related information in a multilanguage format
      through a touchscreen kiosk. DESIGN: Three touchscreen kiosks were programmed
      with information on 10 health topics translated into five languages: Chinese,
      Bengali, Gujarati, Urdu and Mirpuri Punjabi. Information was provided orally and
      in written format. Over an 18-month period the touchscreens were rotated between
      settings including health centres and libraries, located in deprived areas of
      Leicester, Sheffield and Nottingham. Information was logged on each individual
      user with respect to language used, topic selected, age group and gender of user.
      A number of users were invited to complete a short questionnaire about their use
      and ease of use of the touchscreen. RESULTS: Touchscreens were accessed by 2,456
      people across all ages, 53% of whom were male. Urdu and Gujarati were the most
      frequently accessed languages (37 and 38%, respectively) and Bengali used least
      (9%). There was some variation in use by setting. Most of the 508 people
      questioned who had used the touchscreen found it easy to use. Ease of use was
      related to home computer use and to being younger in age. The five most popular
      topics accessed by 12% or more users were stress, diabetes, blood pressure,
      healthy eating and exercise. Topic choice varied by language used by males but
      not by females. CONCLUSION: Touchscreens providing health information in ethnic
      minority languages can be successfully accessed by black and ethnic minority
      groups, particularly those living in deprived areas. Touchscreens proved
      acceptable to, and were used by, the targeted audience.

PMID- 16087454
TI  - Gender and ethnic differences in the co-occurrence of adolescent risk behaviors.
AB  - OBJECTIVES: We consider gender and ethnic differences in the co-occurrence of
      adolescent behaviors related to health and well-being. DESIGN: Using a nationally
      representative sample of adolescents in the National Longitudinal Survey of Youth
      (1997-2000), we examine behavior among students as well as school drop-outs. We
      use latent class models (LCMs) to identify subpopulations of adolescents with
      similar patterns of co-occurring behaviors. The generalizability of the findings
      for African American adolescents in the 1970s is considered using a sample of
      inner-city youth from the Pathways to Adulthood Survey. RESULTS: For all ethnic
      groups, we find a subpopulation with 'problem behavior' characteristics (in which
      early sexual initiation, alcohol use, smoking, marijuana use, and truancy are all
      highly prevalent). This cluster is most common among European American
      adolescents and among young men. A subpopulation characterized by behaviors often
      leading to poor social outcomes (e.g. truancy, early sexual initiation and
      fighting) is most common for African American adolescents, especially young
      African American men. CONCLUSION: Our findings suggest that multi-factorial
      interventions which address the interrelationships between all of the behaviors
      are relevant regardless of gender or ethnicity. However, the ethnic and gender
      differences in the likelihood of specific patterns of interrelationships
      highlight the importance of considering the ethnic and gender composition of a
      population when developing future research and interventions.

PMID- 16087455
TI  - The influence of ethnicity on patient satisfaction.
AB  - OBJECTIVE: To investigate the influence of ethnicity on patient satisfaction with
      hospitalization care. METHODS: We conducted a random selection, cross-sectional
      study. Data were collected by telephone interviews over a three-year period
      utilizing a 16-question survey. Patients were excluded from the study if they
      were admitted for an obstetric visit, physical rehabilitation, or psychiatric
      illness or if we were unable to reach them by telephone. We used logistic
      regression to compare ethnicity with the responses for each of the 16 questions
      while controlling for three confounders (age, gender, and insurance status). For
      each question, patient responses of excellent and very good were considered
      satisfied. Patient responses of good, fair, and poor were considered not
      satisfied. RESULTS: We surveyed 7,795 patients. Compared to African-Americans,
      non-Hispanic white Americans were significantly older, included more males, and
      were insured by Medicaid less often (p < 0.05). Using multivariate analysis, we
      found that seven of the 16 questions exhibited significant satisfaction
      differences. African-Americans expressed significantly less satisfaction for two
      of six questions related to nursing care, two of three questions related to
      entire staff care, one of two question related to physician care, and one of
      three questions related to overall satisfaction (p < 0.05). However, African
      Americans expressed significantly more satisfaction for one question related to
      nursing care. There was no difference between the two groups for nine of the 16
      questions, including both questions regarding communication and coordination.
      CONCLUSION: African-Americans reported significantly lower rates of satisfaction
      compared to non-Hispanic white Americans for six of 16 questions regarding
      satisfaction during hospitalization care.

PMID- 16087457
TI  - Commentary: next steps for graduated licensing.

PMID- 16087456
TI  - Incidence of mental disorders in second-generation immigrants in sweden: a four
      year cohort study.
AB  - BACKGROUND: Few studies have investigated mental health among second-generation
      immigrants who have reached adulthood. The aim of this study was to examine
      whether second-generation adult immigrants have a higher risk of being
      hospitalised for mental disorders than the Swedish majority population after
      adjustment for socio-economic status. METHODS: In total 1.9 million Swedish-born
      women and men aged 16-34 were followed from 1 January 1995 to 31 December 1998
      for first hospital admissions for mental disorders, categorised in four main
      diagnosis groups. Second-generation immigrants comprised four groups and the
      Swedish majority population was used as reference group. Cox proportional hazard
      models were used to analyse the data. RESULTS: Second-generation immigrants with
      one parent born in Sweden and second-generation Finns had higher risks of being
      hospitalised for psychotic disorders, affective disorders, neurotic disorders,
      and personality disorders than the Swedish majority population. For second
      generation Finns the age- and sex-adjusted hazard ratio for psychotic disorders
      was 2.42 (CI = 2.09-2.80). No significant hazard ratios were found for second
      generation labour immigrants. For second-generation refugees the risk of being
      hospitalised was higher than for the Swedish majority population but only for
      psychotic disorders. All results remained significant and decreased only slightly
      after adjustment for income and education. CONCLUSIONS: Many groups of second
      generation immigrants have a higher risk of being hospitalised for mental
      disorder than the majority population. With increasing global migration it is
      crucial for all industrialised countries to take measures to improve mental
      health among second-generation immigrants.

PMID- 16087458
TI  - Sixteen-year-old drivers in fatal crashes, United States, 2003.
AB  - OBJECTIVE: Key features of graduated licensing were introduced in 46 states and
      the District of Columbia between 1993 and 2003. State evaluations consistently
      have reported positive overall effects and positive effects of nighttime and
      passenger restrictions. Sixteen year-olds are the main target of graduated
      licensing, and the present study investigated changes in their fatal crash
      involvement and crash characteristics that have taken place nationally during
      1993-2003. By looking at 16 year-olds nationally, the study does not constitute a
      direct test of the effect of graduated licensing laws per se. METHODS: Data on
      fatal crashes were obtained from the Fatality Analysis Reporting System. Sixteen
      year-olds were compared with older drivers. RESULTS: During these years, the
      extent to which 16-year-old drivers were in fatal crashes decreased substantially
      compared with older age groups. The drop in the per capita crash rate for 16 year
      olds was 26%. The major change was a reduction in crashes involving transporting
      young passengers, especially in jurisdictions with restrictions that target these
      crashes. There was no change in the proportion of fatal late-night crashes even
      in states restricting this activity. CONCLUSIONS: There has been some progress
      nationally in reducing the crash problem for 16 year-olds, but this still is a
      big problem. To achieve further progress, the gaps and weaknesses in present
      graduated licensing laws will need to be addressed.

PMID- 16087459
TI  - Driving while impaired (DWI) by alcohol convictions among alcohol, cocaine, and
      cannabis clients in treatment.
AB  - OBJECTIVE: Although studies have demonstrated that clients in treatment for
      alcohol abuse are more at risk of driving while impaired (DWI) by alcohol than
      normal licensed drivers from the general population, no research was found on DWI
      convictions among those in treatment for abusing cannabis or cocaine. The purpose
      of this article is to compare DWI convictions among clients in treatment for
      alcohol, cannabis, cocaine, or various combinations of these substances, compared
      to a matched population control group. METHOD: A stratified random sample of
      driver records was drawn from seven client groups who sought treatment in 1994
      for alcohol, cannabis, cocaine, or any combination of these substances (n = 445).
      A random sample of drivers, frequency matched by age and sex (n = 566), served as
      control subjects. RESULTS: Logistic regression analysis, controlling for sex and
      age, was conducted to assess whether DWI convictions were elevated for each of
      the client groups, compared to controls. Two sets of analyses were conducted,
      before treatment (from 1985 to 1993) and after treatment (from 1995 to 2000). In
      the time period before treatment, every drug group except the "cannabis only"
      group had significantly more DWI convictions than controls (p < .05). In the
      period after treatment, the "alcohol only," "cocaine only," "alcohol and
      cocaine," and the "cocaine and cannabis" groups still had significantly more DWI
      convictions than controls (p < .05). CONCLUSION: The results show that DWI
      convictions are elevated among those who abused cocaine but not among those who
      abused cannabis. The results suggest that cross-addiction of alcohol and cocaine
      is common, and problematic drinking among cocaine clients can go undetected when
      clients are being diagnosed for treatment.

PMID- 16087460
TI  - Young people driving after drinking and riding with drinking drivers: drinking
      locations--what do they tell us?
AB  - OBJECTIVE: The present study investigated the extent to which drinking in
      specific locations and heavy drinking mediated the effects of overall alcohol use
      on driving after drinking (DD) and riding with drinking drivers (RWDD) among
      young people. Additionally, this study examined the relationships among
      ethnicity, gender, drinking in specific locations, and DD and RWDD. METHOD: Using
      random-digit dialing procedures, participants were recruited to take part in a
      telephone survey in California, United States of America. Participants were 1,534
      youth, ages 15-20 years (mean age = 17.6). Latinos, African Americans, and Asian
      Americans were over-sampled to allow cross-group comparisons. Along with
      background characteristics, overall alcohol use, heavy drinking, drinking in
      specific locations, DD, and RWDD were measured. RESULTS: Latent variable
      structural equation modeling showed that European Americans, males, older
      adolescents, those who have a driver license, and those who drive more often were
      more likely to report drinking alcohol in the past year. Heavy episodic drinking
      and drinking in cars increased both DD and RWDD. Drinking in restaurants also
      increased DD. The effects of overall alcohol consumption on DD were entirely
      mediated through heavy episodic drinking and drinking in restaurants and cars.
      Alcohol consumption had both direct and indirect effects on RWDD. With the
      exception of being Latino and frequency of driving, the effects of the background
      variables on RWDD were all entirely mediated through alcohol consumption.
      CONCLUSIONS: Heavy drinking and drinking in specific locations appeared to be
      important unique predictors of both DD and RWDD. In light of the relationship
      between drinking in restaurants and in cars, and DD, prevention programs and
      policies aimed at underage drinking should focus on developing more effective
      responsible beverage service programs, increasing compliance with laws limiting
      alcohol sales to youth, and enforcing graduated driver licensing and zero
      tolerance laws.

PMID- 16087461
TI  - Drink-driving and perceptions of legally permissible alcohol use.
AB  - OBJECTIVE: The leading cause of death for young people in developed countries is
      road traffic crashes, a large proportion of which are attributable to drink
      driving. The aims of the study were to estimate the prevalence of drink-driving
      and drink-riding in a sample of New Zealand university students, and to identify
      potential risk factors, in particular, students' perceptions of legally
      permissible consumption before driving. METHODS: Participants were 1,564 survey
      respondents (82% response, mean age = 20.5 years) who were asked to indicate
      whether they had driven after having "perhaps too much to drink to be able to
      drive safely," if they had been a passenger in a vehicle "where the driver had
      perhaps too much to drink to be able to drive safely," and how many standard
      drinks they could consume in one hour and legally drive a car. An estimated blood
      alcohol concentration was computed and compared with legal limits. RESULTS: Drink
      driving (past four weeks) was reported by 3.4% of women and 8.4% of men. Drink
      riding (past four weeks) was reported by 7.0% of women and 11.5% of men.
      Estimated blood alcohol concentrations from students' reports of how much they
      could drink in one hour and be below the legal limit of 0.08 g/ml, showed that
      most respondents dramatically underestimated permissible consumption; only 5.8%
      overestimated it. CONCLUSIONS: This may be a case where misperception of a public
      health message serves the public good. Further reductions in drink-driving/riding
      will require attention to transport needs, more visible enforcement of existing
      legislation, and modification of youth drinking behavior.

PMID- 16087462
TI  - In-car cell phone use and hazards following hands free legislation.
AB  - OBJECTIVE: A new law took effect in Finland at the beginning of 2003 which
      prohibits the handheld use of mobile phones while driving a motor vehicle. The
      purpose of this study was to assess the impact of the law on phone usage and self
      reported safety during the first few months and 16 months later to determine
      whether the initial level of compliance with the law had been sustained. METHODS:
      Data were collected by Gallup home poll before (spring 2002) and after
      legislation took effect (spring 2003 and 2004). A representative sample of
      drivers who owned a cell phone (n = 836 to 966) was interviewed each time. On
      road observations were also collected in four cities for 2003 and 2004. RESULTS:
      Just after the law, 97% of drivers were aware of the new hands free legislation.
      In sharp contrast to the pre-law rate of 16%, 43% reported not using the phone
      while driving immediately after the law and 41% one year later. The occasional
      users especially reduced their use of phones while driving. The law was
      correlated to reductions in self-reported handheld use of cell phones while
      driving, from 55.6% pre-law to 15.2% immediately after passage. In spite of this
      change, however, the hands free legislation did not reduce self-reported
      involvement of Finnish drivers in phone-related hazards. Handheld usage was still
      lower in 2004 than pre-law (20.0%), but the 32% increase from 2003 was
      significant. Observational data collected in Finland in 2003 and 2004 showed an
      even higher upward trend in handheld use (87% increase, from 3.1% to 5.8%; pre
      law data were not available), and matched a similar increase reported by McCartt
      and Geary (2004) in their observational evaluation of New York's handheld mobile
      phone law. CONCLUSION: The self-reports indicate that the hands-free law reduced
      handheld phone use, among occasional users especially, but did not reduce phone
      related hazards. The effect of the law on phone use substantially declined within
      one year.

PMID- 16087463
TI  - Unlicensed drivers and car crash injury.
AB  - OBJECTIVE: Previous studies have indicated that unlicensed drivers are more
      likely to engage in risky driving behaviors, and are more likely than licensed
      drivers to be at fault and more seriously injured when involved in a crash.
      However, the prevalence of unlicensed drivers in the general driving population
      has not been measured, and the risk of an unlicensed driver being involved in an
      injury crash has not been quantified. We examined the association between
      unlicensed driving and car crash injury using data from a population-based case
      control study. METHODS: The study population was the drivers of all cars on
      public roads in the Auckland region. Cases were 571 vehicles involved in a crash
      resulting in any occupant being hospitalised or killed, from the study base,
      during the recruitment period. Controls were 588 vehicles selected from the
      driving population using a random cluster sampling method. The drivers of all
      vehicles completed a structured interview covering multiple potentially crash
      related factors. RESULTS: Driving unlicensed was reported by 12% of case and 1%
      of control drivers. Unlicensed drivers were at significantly higher risk of car
      crash injury than those holding a valid licence (odds ratio 11.1, 95% confidence
      interval 4.2 to 29.7) after adjustment for age and sex. After further adjustment
      for education level, ethnicity, driving exposure, time of day, sleepiness score,
      year of vehicle manufacture, passenger carriage, seatbelt use, blood alcohol
      concentration, and travelling speed at time of crash, the increased risk was
      still present but no longer significant (OR 3.9, 95% CI 0.7-22.4). CONCLUSIONS:
      Unlicensed drivers are a high risk group for car crash injury after taking other
      crash-related risk factors into account. Strategies to reduce unlicensed driving
      may therefore facilitate reductions in road crashes, although further work is
      needed in this area.

PMID- 16087464
TI  - An exploratory study on the predictive elements of passing on-the-road tests for
      disabled persons.
AB  - OBJECTIVES: Driving evaluations are performed by Occupational Therapists to
      evaluate drivers with disability. They include both off-road and on-road
      assessments. Many aspects of driving are examined during the on-road assessment.
      The main objective of this study is to identify the elements of the Occupational
      Therapy on-road driving assessment that are most predictive of the overall
      driving evaluation. METHODS: This retrospective cohort study took place at a
      provincially approved Driving Assessment Program. Records of 700 participants
      with various disabilities who completed a driving assessment between 1995 and
      2003 were reviewed. Only clients who completed the on-road assessment were
      included in the study. At our center, 11 driving elements comprised of 34 items
      were used as independent variables and rated as pass (acceptable or good) or fail
      (borderline or poor). Analysis was completed with descriptive statistics and use
      of logistic regression to identify elements that contributed most significantly
      to the overall driving evaluation. RESULTS: A total of 628 clients completed the
      on-road assessment with an overall pass rate of 50%. Logistic regression modeling
      identified poor anticipation of road hazards, observation of environment,
      improper stopping position, poor visual scanning, poor knowledge of the rules of
      the road, and increasing age as predictive of failure for all participants.
      Further analysis grouped subjects according to disability to identify
      similarities and differences between pass/fail predictors. Both similarities and
      differences in predictive elements were found between cognitive and physical
      diagnostic groupings. Most notably, the physical diagnostic grouping showed that
      cognitive, not physical elements of the on-road test, predicted failure of the
      overall driving evaluation. CONCLUSIONS: Of the 11 elements considered in the on
      road evaluation, specific cognitive ones such as anticipates potential hazards,
      scanning, observes for pedestrians, and proper stopping position tend to
      contribute more to the prediction of pass or fail than others. These elements
      should be considered as components of on-road assessments by other Driving
      Assessment Programs.

PMID- 16087465
TI  - Impact of infrastructure characteristics on road crashes on two-lane highways.
AB  - OBJECTIVE: The main purpose of this study is to estimate and quantify the
      contribution of the infrastructure to highway crashes and to develop an
      infrastructure coefficient, that represents the overall characteristics of the
      highway and could be used as an independent variable in a crash-prediction model.
      METHODS: The infrastructure is defined in this study as the highway and its
      geometric features, including alignment, road-side elements, sight-distances,
      presence of guardrails, access-points, roadway consistency, and additional
      variables that measure the overall quality of the highway alignment and elements.
      The analysis and developments are conducted for two-lane rural highways. The
      approach taken is to identify the high crash-rate roads, those with crash rates
      above 0.25 crashes per million vehicle-km, by Smallest Space Analysis. This type
      of analysis allows the aggregation of higher crash-rate roads versus lower-crash
      rate roads only by their infrastructure coefficients, without consideration of
      their crash records. RESULTS: Crash rates that are attached by Smallest Space
      Analysis to the group of roads that had less desirable infrastructure features
      show a high correlation between the same roads and high crash rates vs.
      identified better infrastructures and low crash rates. Further analysis shows
      that low crash-rate infrastructure, as defined in this study for two-lane rural
      highways, can reduce the crash rate by 44% versus high crash-rate infrastructure,
      at the 99% confidence level, which is almost a certainty. A model for the
      prediction of crash rates based on a proposed infrastructure coefficient is
      calibrated and presented. CONCLUSIONS: It is suggested that this model be used in
      evaluating alternatives for new highways or in improving the alignment and road
      features of existing highways.

PMID- 16087466
TI  - Transit bus operator performance and attitudes toward a collision warning system:
      results of a simulator experiment.
AB  - OBJECTIVE: This article discusses the results of a simulator experiment to
      examine the efficacy of a collision warning system for transit bus operators.
      METHODS: Bus operators from a major metropolitan transit agency were assigned to
      one of three conditions: a collision warning system with a visual-only driver
      vehicle interface, a collision warning system with a visual and auditory driver
      vehicle interface, or no collision warning system (baseline). Operators were
      exposed to a critical event at the end of the simulation, in which a vehicle
      suddenly stopped in front of the bus while the operator was distracted by an in
      vehicle task. Upon completing the experiment, operators who used the collision
      warning system were asked about their experience using the system, as well as
      whether or not they would like such a system in real life. RESULTS: Experimental
      results revealed new information about transit bus operator performance, but
      indicated no statistically significant differences among the three conditions.
      Subjective data indicated that operators had a positive attitude toward collision
      warning system usage. Operators generally liked the collision warning system and
      felt that a system such as the one used in the experiment would help them in
      avoiding crashes in the real world. CONCLUSIONS: These findings suggest that a
      collision warning system for transit bus operators is feasible from the
      perspective of user acceptance. However, several technical areas still need to be
      resolved.

PMID- 16087467
TI  - Parametric analysis of vehicle design influence on the four phases of whiplash
      motion.
AB  - OBJECTIVE: The objective is to establish a basis for motor vehicle test
      requirements that measure component contributions to Whiplash Associated
      Disorders (WAD). METHODS: Selected vehicle design features are evaluated with
      regard to their relative contributions to WAD measures. The motion of the
      occupant cervical spine associated with WAD is divided into four phases:
      retraction, extension, rebound, and protraction. Injury measures from the
      literature (NIC, extension moment, N(km), and flexion moment) represent the
      injury potential during each of these phases. Four vehicle design factors that
      affect WAD motion (vehicle stiffness, seat stiffness, head restraint height and
      head restraint backset) were evaluated for their contributions to the injury
      measures. A detailed 50th percentile male model with a biofidelic neck was used
      in a 100-run Monte Carlo analysis of a rear impact, varying the design factors
      across the values documented in the literature. Total energy was held constant
      and Delta V was 10 kph. RESULTS: Vehicle stiffness has a strong influence on the
      retraction (70%), rebound (43%), and protraction (47%) phases. Headrest backset
      demonstrates a strong influence on the extension (49%) and rebound (39%) phases.
      CONCLUSIONS: For WAD protection rating, the vehicle should be viewed as a system
      whereby the complex interactions among the vehicle, seat, and occupant
      characteristics all contribute to the WAD potential.

PMID- 16087468
TI  - Variability in vehicle and dummy responses in rear-end collisions.
AB  - OBJECTIVE: The objective of this study was to quantify the occupant response
      variability due to differences in vehicle and seat design in low-speed rear-end
      collisions. METHODS: Occupant response variability was quantified using a BioRID
      dummy exposed to rear-end collisions in 20 different vehicles. Vehicles were
      rolled rearward into a rigid barrier at 8 km/h and the dynamic responses of the
      vehicle and dummy were measured with the head restraint adjusted to the up most
      position. In vehicles not damaged by this collision, additional tests were
      conducted with the head restraint down and at different impact speeds. RESULTS:
      Despite a coefficient of variation (COV) of less than 2% for the impact speed of
      the initial 8 km/h tests, the vehicle response parameters (speed change,
      acceleration, restitution, bumper force) had COVs of 7 to 23% and the dummy
      response parameters (head and T1 kinematics, neck loads, NIC, N(ij) and N(km))
      had COVs of 14 to 52%. In five vehicles tested multiple times, a head restraint
      in the down position significantly increased the peak magnitude of many dummy
      kinematic and kinetic response parameters. Peak head kinematics and neck kinetics
      generally varied linearly with head restraint back set and height, although the
      neck reaction moment reversed and increased considerably if the dummy's head
      wrapped onto the top of the head restraint. CONCLUSIONS: The results of this
      study support the proposition that the vehicle, seat, and head restraint are a
      safety system and that the design of vehicle bumpers and seats/head restraint
      should be considered together to maximize the potential reduction in whiplash
      injuries.

PMID- 16087470
TI  - Pedestrian lower limb injury criteria evaluation: a finite element approach.
AB  - OBJECTIVE: In pedestrian traumas, lower limb injuries occur under lateral
      shearing and bending at the knee joint level. One way to improve injury
      mechanisms description and consequently knee joint safety is to evaluate the
      ultimate shearing and bending levels at which ligaments start being injured.
      METHODS: As such data cannot easily and accurately be recorded clinically or
      during experiments, we show in this article how numerical simulation can be used
      to estimate such thresholds. This work was performed with the Lower Limb Model
      for Safety (LLMS) in pure lateral bending and shearing conditions, with an
      extended range of impact velocities. RESULTS: One result concerns the ultimate
      knee lateral bending angle and shearing displacement measurements for potential
      failure of ligaments (posterior cruciate, medial collateral, anterior cruciates
      and tibial collateral). They were evaluated to be close to 16 degrees and 15 mm,
      respectively. CONCLUSION: The lower leg model used in this study is an advanced
      FE model of the lower limb, validated under various situations. Its accurate
      anatomical description allows a wide range of applications. According to the
      validity domain of the model, it offered a valuable tool for the numerical
      evaluation of potential injuries and the definition of injury risk criterion for
      knee joint.

PMID- 16087469
TI  - Pedestrian injuries: viscoelastic properties of human knee ligaments at high
      loading rates.
AB  - OBJECTIVE: Accidents involving pedestrians are very common, and often lead to
      severe injuries to the lower extremities. In a large portion of pedestrian
      automobile collisions, knee ligament injuries are sustained. In this study, the
      viscoelastic properties of the four major human knee ligaments were investigated
      at loading rates representative for pedestrian-automobile collisions. METHODS:
      Bone-ligament-bone specimens were tested in knee distraction loading. The
      collateral ligaments and the separate functional bundles of the cruciate
      ligaments were tested in the anatomical position corresponding to a fully
      extended knee. A series of step-and-hold tests and ramp tests at different rates
      were conducted to characterize the time-dependent behavior of the knee ligaments
      for deformation rates associated with the pedestrian impact loading environment.
      The quasi linear viscoelastic (QLV) theory was used to describe the structural
      response of the knee ligaments and averaged parameters for this model were
      determined. RESULTS: The QLV theory was found to be applicable for the time range
      that is relevant for pedestrian-automobile collisions. The structural behavior of
      the knee ligaments was found to be particularly rate-sensitive for high
      elongation rates, as occur during these collisions. The ligament stiffness was
      found to increase with age for both the collateral ligaments and with weight for
      the medial collateral ligament. CONCLUSIONS: For the loading conditions that are
      relevant for pedestrian-automobile collisions, the use of the QLV model for the
      description of the mechanical behavior of knee ligaments is appropriate. The rate
      sensitivity is particularly important for these extreme loading conditions. The
      relaxation behavior was found to be consistent between different ligament types
      and samples. Variations due to donor anthropometry were found predominantly for
      the instantaneous elastic behavior.

PMID- 16087471
TI  - Habitual exercise induced resistance to oxidative stress.
AB  - We investigated whether habitual exercise (HE) modulates levels of oxidative DNA
      damage and responsiveness to oxidative stress induced by renal carcinogen Fe
      nitrilotriacetic acid (Fe-NTA). During a ten week protocol, two groups of rats
      either remained sedentary or underwent swimming for 15--60 min per day, 5 days
      per week, with or without a weight equivalent to 5% of their body weight. Then we
      injected Fe-NTA and sacrificed the rats 1 h after the injection. We determined
      the activity of superoxide dismutase (SOD) in diaphragm and kidney, evaluated
      levels of 8-hydroxydeoxyguanosine (8OHdG), catalase, and glutathione peroxidase,
      and assayed OGG1 protein levels in kidney. SOD activity in the diaphragm and
      kidney was increased in HE rats. By itself, HE had no effect on the level of
      8OHdG, but it did significantly suppress induction of 8OHdG by Fe-NTA, and the
      amount of suppression correlated with intensity of exercise. These results
      suggest that HE induces resistance to oxidative stress and, at least at the
      initiation stage, inhibits carcinogenesis.

PMID- 16087472
TI  - Cyclosporin A generates superoxide in smooth muscle cells.
AB  - Cyclosporin A (CsA) generates superoxide in smooth muscle cells. Our earlier
      studies have demonstrated that the increase in the vasopressin type 1 receptor
      induced in vascular smooth muscle cells in the presence of CsA is probably due to
      superoxide (Krauskopf et al., J Biol Chem 278, 41685-41690, 2003). This increase
      in vasopressin receptor is likely at the base of increased vascular
      responsiveness to vasoconstrictor hormones and hypertension induced by CsA. Here,
      we demonstrate that CsA produces superoxide. In addition, our data show that
      superoxide generation does not originate from the major cellular superoxide
      generating systems NAD(P)H oxidase or xanthine oxidase. Our results suggest that
      the side effects of CsA could be diminished with the help of SOD mimetic drugs.

PMID- 16087473
TI  - Isolated respiring heart mitochondria release reactive oxygen species in states 4
      and 3.
AB  - Isolated mitochondria respiring on physiological substrates, both in state 4 and
      3, are reported to be or not to be a source of reactive oxygen species (ROS). The
      cause of these discrepancies has been investigated. As protein concentration was
      raised in in vitro assays at 37 degrees C, the rate of H2O2 release by rat heart
      mitochondria supplemented with pyruvate/malate or with succinate (plus rotenone)
      was shown to increase (0.03-0.15 mg protein/ml), to decrease (0.2-0.5 mg
      protein/ml) and to be negligible (over 0.5 mg protein/ml). The inhibition of
      mitochondrial respiration (with rotenone or antimycin A) or the increase in the
      oxygen concentration dissolved in the assay medium allowed an enhancement of ROS
      production rate throughout the studied range of protein concentrations. In
      mitochondria respiring in state 3 on pyruvate/malate or on succinate (plus
      rotenone), ROS release vanished for protein concentrations over 0.5 or 0.2 mg/ml,
      respectively. However, ROS production rates measured with low protein
      concentrations (below 0.1 mg/ml) or in oxygen-enriched media were similar or even
      slightly higher in the active respiratory state 3 than in the resting state 4 for
      both substrates. Consequently, these findings indicate that isolated
      mitochondria, respiring in vitro under conditions of forward electron transport,
      release ROS with Complex I- and II-linked substrates in the resting condition
      (state 4) and when energy demand is maximal (state 3), provided that there is
      sufficient oxygen dissolved in the medium.

PMID- 16087474
TI  - Estimation of lipoperoxidative damage and antioxidant status in diabetic
      children: relationship with individual antioxidants.
AB  - Increased oxidative stress has emerged as a potential mechanism implicated in the
      pathogenesis, progression and cell dysfunction associated with many diseases
      including diabetes. In routine clinical practice, the estimation of the degree of
      oxidative damage and antioxidant status, even in paediatric patients, by
      appropriate techniques appears to be of interest. The aim of this study was to
      reliably identify patients with increased oxidant stress and/or reduced
      antioxidant defence mechanisms with a small blood sample and verify the
      applicability to the study of diabetic children (DC) at clinical onset of the
      disease. In 1-ml blood samples from 30 DC and 34 controls, techniques for
      accurately measuring malondialdehyde (MDA) concentrations in plasma and
      erythrocytes (using HPLC analysis with fluorometric detection), total radical
      antioxidant potential (TRAP) and blood plasma oxidizability were adapted and
      validated. Plasma alpha-tocopherol (HPLC), uric acid and sulfhydryl (SH) groups
      were also determined. At clinical onset of diabetes a significant reduction in
      plasma TRAP values (P<0.01) was observed in DC compared with controls. Similarly,
      a significant fall in individual antioxidant levels (alpha-tocopherol/total
      lipids, uric acid and protein SH) was noted in plasma of DC. Highly significant
      increases were found in both plasma and erythrocyte MDA levels in DC (p-MDA:1.7+/
      0.2 microM; er-MDA: 7.2+/-0.7 nmol/g Hb) compared with controls (p-MDA:0.86+/
      0.09 microM; P<0.0003; er-MDA:3.8+/-0.2 nmol/g Hb, P<0.0001). Plasma MDA and
      triglyceride levels correlated directly only in DC (P<0.001). Whole plasma
      oxidizability was significantly higher in DC than in controls (P<0.0001) and this
      parameter correlated significantly with plasma cholesterol and triglyceride
      concentrations (P<0.0001). The micromethods adapted and applied to the
      simultaneous detection of lipid peroxidation products and antioxidant status
      permit accurate and reliable assessment of the oxidative stress process in small
      plasma samples. Our results clearly show systemic peroxidative damage associated
      with insufficient defence mechanisms against ROS to be already present at
      clinical onset of type 1 diabetes mellitus in children and adolescents.

PMID- 16087475
TI  - Effect of catecholestrogen administration during adriamycin-induced
      cardiomyopathy in ovariectomized rat.
AB  - The therapeutical beneficial effect of estrogen-derived metabolites or
      catecholestrogens is controversial. These molecules are produced during estrogen
      therapy based on 17-beta-estradiol treatment. The metabolization of 17-beta
      estradiol is carried out in brain, kidney or liver, and triggers different
      products such as 2- and 4- hydroxyestradiol (2OH and 4OH). These products have
      shown antioxidant properties against oxidative stress (OS) in several
      experimental models. Different noxious side effects related to those metabolites
      have also been observed upon estrogen therapy. In this sense, catecholestrogens
      seem to be implicated in tumoral and mutagenic process after long treatment with
      estrogens substitutive therapy. In our study, we have verified that 2OH and 4OH
      have antioxidant and cardioprotective effects against adriamycin (AD)-induced
      cardiomyopathy in ovariectomized (OVX) rats. Catecholestrogens diminished the
      lipid peroxides and carbonyl protein (CO) content, and different enzymes related
      to cell injury (creatinine kinase, lactate dehydrogenase, aspartate
      aminotransferase, alanine aminotransferase) in cardiac tissue from OVX-, AD-, and
      OVX+AD-treated rats. All these changes were correlated to a recovery on reduced
      glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and
      catalase (CAT) in heart tissue. The present study showed that 2OH and 4OH reduced
      all the parameters related to OS, antioxidant depletion and cardiac injury in OVX
      rats treated or not with AD.

PMID- 16087476
TI  - Total antioxidant capacity assay of human serum using copper(II)-neocuproine as
      chromogenic oxidant: the CUPRAC method.
AB  - BACKGROUND: Tests measuring the combined antioxidant effect of the nonenzymatic
      defenses in biological fluids may be useful in providing an index of the
      organism's capability to counteract reactive species known as prooxidants, resist
      oxidative damage and combat oxidative stress-related diseases. The selected
      chromogenic redox reagent for the assay of human serum should be easily
      accessible, stable, selective, respond to all types of biologically important
      antioxidants such as ascorbic acid, alpha-tocopherol, beta-carotene, reduced
      glutathione (GSH), uric acid and bilirubin, regardless of chemical type or
      hydrophilicity. Currently, there is no rapid method for total antioxidant assay
      of human serum meeting the above criteria. METHODS: Our recently developed cupric
      reducing antioxidant capacity (CUPRAC) spectrophotometric method for a number of
      polyphenols and flavonoids using the copper(II)-neocuproine reagent in ammonium
      acetate buffer was now applied to a complete series of plasma antioxidants for
      the assay of total antioxidant capacity (TAC) of serum, and the resulting
      absorbance at 450 nm was recorded either directly (e.g. for ascorbic acid, alpha
      tocopherol and glutathione) or after incubation at 50 degrees C for 20 min (e.g.
      for uric acid, bilirubin and albumin), quantitation being made by means of a
      calibration curve. The lipophilic antioxidants, alpha-tocopherol and beta
      carotene, were assayed in dichloromethane (DCM). Lipophilic antioxidants of serum
      were extracted with n-hexane from an ethanolic solution of serum subjected to
      centrifugation. Hydrophilic antioxidants of serum were assayed after perchloric
      acid precipitation of proteins in the centrifugate. RESULTS: The molar
      absorptivities, linear ranges and trolox equivalent antioxidant capacity (TEAC)
      coefficients of the serum antioxidants were established with respect to the
      CUPRAC spectrophotometric method, and the results (TEAC, or TEAC coefficients)
      were evaluated in comparison to the findings of the ABTS/TEAC reference method
      using persulfate as oxidant. As for hydrophilic phase, a linear correlation
      existed between the CUPRAC and ABTS findings (r=0.58), contrary to current
      literature reporting that either serum ORAC or serum ferric reducing antioxidant
      potency (FRAP) does not correlate at all with serum TEAC. The analytical
      responses of serum antioxidants were shown to be additive, enabling a TAC assay.
      The intra- and inter-assay CVs were 0.7 and 1.5%, respectively, for serum.
      CONCLUSIONS: The CUPRAC assay proved to be efficient for glutathione and thiol
      type antioxidants, for which the FRAP test was nonresponsive. The findings of
      CUPRAC completely agreed with those of ABTS-persulfate for lipophilic phase. The
      additivity of absorbances of all the tested antioxidants confirmed that
      antioxidants in the CUPRAC test did not chemically interact among each other so
      as to cause an intensification or quenching of the theoretically expected
      absorbance. As a distinct advantage over other electron-transfer based assays
      (e.g. Folin, FRAP, ABTS, DPPH), CUPRAC is superior in regard to its realistic pH
      close to the physiological pH, favourable redox potential, accessibility and
      stability of reagents and applicability to lipophilic antioxidants as well as
      hydrophilic ones.

PMID- 16087477
TI  - Analysis of 8-hydroxydeoxyguanosine among workers exposed to diesel particulate
      exhaust: comparison with urinary metabolites and PAH air monitoring.
AB  - Oxidative DNA damage and repair, as measured by 8-hydroxy-2'-deoxyguanosine (8
      OHdG) in urine and DNA samples were studied in association with work-related
      diesel exhaust exposure among garage and waste collection workers. Seasonal
      variations of the urinary 8-OHdG levels in pre- and two post-workshift urine
      samples of 29 exposed workers and 36 control persons were evaluated. The mean+/
      SE levels of post-workshift 8-OHdG (mumol/mol crea) were 1.52+/-0.44 in winter
      and 1.61+/-0.33 in summer for the exposed workers, and 1.56+/-0.61 in winter and
      1.43+/-0.49 in summer for the controls, respectively. No significant difference
      in the urinary 8-OHdG levels between exposed workers and control subjects in
      winter (p=0.923) and summer (p=0.350) was observed. A linear mixed model,
      adjusted for years of employment, age, ex/non-smoking and BMI, indicated no
      significant dose exposure-relationships between the urinary 8-OHdG and 15 PAH air
      concentrations nor between the 8-OHdG and 7 PAH monohydroxy-metabolites analyzed
      in the same workers. 8-OHdG was also analyzed in the mononuclear cell DNA of 19
      exposed and 18 control subjects. The mean value of 8-OHdG/non-modified 2'
      deoxyguanosine (8-OHdG/105 dG+/-SE) were 4.89+/-0.17 for the exposed and 4.11+/
      0.16 for the control persons, which showed no correlation with the urinary 8-OHdG
      levels (r=0.01, n=28, P=0.96). The PAH exposure at workplaces was mainly composed
      of volatile compounds, particularly naphthalene, suggesting low exposure through
      the respiratory tract and a low effect of PAH in ROS induction.

PMID- 16087478
TI  - Effects of aldehydes on CD36 expression.
AB  - INTRODUCTION: During the oil frying process lipid peroxidation compounds are
      formed. These products can modulate gene expression and alter cellular behaviour.
      The cellular uptake of oxidized LDL, a key step in the development of
      atherosclerosis, is mediated by the CD36 scavenger receptor, whose expression is
      down-regulated by alpha-tocopherol. OBJECTIVE: To determine the effects of water
      soluble aldehydes, obtained from thermally oxidized sunflower oil on the
      expression of CD36 scavenger receptor in human monocytes (THP-1 cells). We also
      wanted to study the effects of alpha-tocopherol on CD36 expression in the
      presence of water-soluble aldehydes. MATERIALS AND METHODS: Sunflower oil was
      heated in a frying pan, at 180--200 degrees C for 40 min, water-soluble aldehydes
      were isolated, and the content of thiobarbituric acid reacting substances (TBARS)
      was determined. THP-1 monocytes were cultured in RPMI medium during 24 h and
      incubated with increasing concentrations of the water-soluble aldehydes (ranging
      from 0.05 to 1 microM) and with or without 50 microM of alpha-tocopherol. In
      parallel, THP-1 cells were cultured with the same volume of an extract obtained
      from non-oxidized oil or distilled water. The CD36 expression at the cell surface
      was studied with fluorescence-activated cell sorting (FACS). RESULTS: Monocytes
      incubated in a medium containing water-soluble aldehydes, showed a dose dependent
      increase in the expression of the CD36 protein on the cell surface, compared to
      with the control groups. When the cells were treated simultaneously with 50
      microM of alpha-tocopherol a significant reduction in the expression of the CD36
      protein was observed. CONCLUSION: Water-soluble aldehydes, extracted from
      thermally oxidized culinary oil, increase the expression of CD36. This effect is
      partially decreased by the presence of alpha-tocopherol.

PMID- 16087479
TI  - NADH oxidase activity of rat liver xanthine dehydrogenase and xanthine oxidase
      contribution for damage mechanisms.
AB  - The involvement of xanthine oxidase (XO) in some reactive oxygen species (ROS) 
      mediated diseases has been proposed as a result of the generation of O*- and H2O2
      during hypoxanthine and xanthine oxidation. In this study, it was shown that
      purified rat liver XO and xanthine dehydrogenase (XD) catalyse the NADH
      oxidation, generating O*- and inducing the peroxidation of liposomes, in a NADH
      and enzyme concentration-dependent manner. Comparatively to equimolar
      concentrations of xanthine, a higher peroxidation extent is observed in the
      presence of NADH. In addition, the peroxidation extent induced by XD is higher
      than that observed with XO. The in vivo-predominant dehydrogenase is, therefore,
      intrinsically efficient at generating ROS, without requiring the conversion to
      XO. Our results suggest that, in those pathological conditions where an increase
      on NADH concentration occurs, the NADH oxidation catalysed by XD may constitute
      an important pathway for ROS-mediated tissue injuries.

PMID- 16087480
TI  - Identification of a radical formed in the reaction mixtures of oxidized
      phosphatidylcholine with ferrous ions using HPLC-ESR and HPLC-ESR-MS.
AB  - Identification of free radicals was performed for the reaction mixtures of
      autoxidized 1,2-dilinoleoylphosphatidylcholine (DLPC) with ferrous ions (or DLPC
      hydroperoxide with ferrous ions) and of DLPC with soybean lipoxygenase using
      electron spin resonance (ESR), high performance liquid chromatography (HPLC)--ESR
      and HPLC--ESR-mass spectrometry (MS) combined use of spin trapping technique. ESR
      measurements of the reaction mixtures showed prominent signals with hyperfine
      coupling constants (a(N)=1.58 mT and a(H)beta=0.26 mT). Outstanding peaks with
      almost same retention times (autoxidized DLPC, 36.9 min; DLPC hydroperoxide, 35.0
      min; DLPC with soybean lipoxygenase, 37.1 min) were observed on the elution
      profile of the HPLC--ESR analyses of the reaction mixtures. HPLC--ESR--MS
      analyses of the reaction mixtures gave two ions at m/z 266 and 179, suggesting
      that 4-POBN/pentyl radical adduct forms in these reaction mixtures.

PMID- 16087481
TI  - Rosmarinic acid inhibits the formation of reactive oxygen and nitrogen species in
      RAW264.7 macrophages.
AB  - Antioxidant action of Rosmarinic acid (Ros A), a natural phenolic ingredient in
      many Lamiaceae herbs such as Perilla frutescens, sage, basil and mint, was
      analyzed in relation to the Ikappa-B activation in RAW264.7 macrophages. Ros A
      inhibited nitric oxide (NO) production and inducible nitric oxide synthase (iNOS)
      protein synthesis induced by lipopolysaccharide (LPS), and also effectively
      suppressed phorbol 12-myristate 13-acetate (PMA)-induced superoxide production in
      RAW264.7 macrophages in a dose-dependent manner. Peroxynitrite-induced formation
      of 3-nitrotyrosine in bovine serum albumin and RAW264.7 macrophages were also
      inhibited by Ros A. Moreover, Western blot analysis demonstrated that LPS-induced
      phosphorylation of Ikappa-Balpha was abolished by Ros A. Ros A can act as an
      effective protector against peroxynitrite-mediated damage, and as a potent
      inhibitor of superoxide and NO synthesis; the inhibition of the formation of
      reactive oxygen and nitrogen species are partly based on its ability to inhibit
      the serine phosphorylation of Ikappa-Balpha.

PMID- 16087482
TI  - The genotypic variation of the antioxidant potential of different tomato
      varieties.
AB  - There is increasing interest in the ability of diets rich in polyphenols to
      modulate age-related diseases and promote healthy ageing. We have conducted a
      pilot experiment with eight tomato varieties to correlate the total antioxidant
      capacity of the tomato variants with the specific constituent flavonoids present.
      A strong correlation was observed with the flavonol rhamnoglucoside rutin but not
      with other flavonoids, such as naringenin chalcone, or hydroxycinnamates, such as
      chlorogenic, which are also present in the tomato. To test the rigor of this
      correlation a second study was undertaken with a further 37 tomato varieties
      selected for low, medium and high rutin levels. We show that the flavonol rutin
      contributes to the greatest extent to the antioxidant capacity of tomatoes and
      suggest that this flavonoid may be a useful target for up-regulation in tomatoes
      in order to improve their antioxidant status.

PMID- 16087484
TI  - Development of a public health programme in Greenland.

PMID- 16087483
TI  - Green tea polyphenol extract attenuates colon injury induced by experimental
      colitis.
AB  - Inflammatory bowel disease (IBD) is characterised by oxidative and nitrosative
      stress, leukocyte infiltration, and up-regulation of intercellular adhesion
      molecule 1 (ICAM-1) expression in the colon. The aim of the present study was to
      examine the effects of green tea extract in rats subjected to experimental
      colitis induced by intracolonic instillation of dinitrobenzene sulphonic acid
      (DNBS). At 4 days after DNBS administration the rats were sacrificed. Treatment
      with green tea extract significantly attenuated diarrhoea and loss of body
      weight. This was associated with a remarkable amelioration of the disruption of
      the colonic architecture, significant reduction of colonic myeloperoxidase (MPO)
      and tumor necrosis factor-alpha (TNF-alpha) production. Green tea extract also
      reduced the appearance of nitrotyrosine immunoreactivity in the colon and reduced
      the up-regulation of ICAM-1.

PMID- 16087486
TI  - Physical activity in leisure-time and risk of cancer: 14-year follow-up of 28,000
      Danish men and women.
AB  - AIM: The preventive effect of physical activity on risk of cancer in general
      remains controversial. This study aimed at assessment of the associations between
      leisure- time physical activity and incidence of cancer in the general population
      of adult men and women. METHODS: 13,216 women and 18,718 men aged 20-93 years
      selected from the general population participated in a health examination
      including a questionnaire with information on physical activity, smoking, alcohol
      intake, postmenopausal hormones, and socioeconomic status. Incident cases of
      cancers where recorded during a follow-up period of 14 years. The six most
      frequent cancer cases in both sexes were included in this analysis. RESULTS: A
      highly significant inverse association was seen between vigorous physical
      activity in leisure time and cancer of the ovary, adjusted rate ratio being 0.33
      (95% CI 0.16-0.67; p = 0.001) for the most physical active women. In men there
      was a highly significant increase for non-melanoma skin cancer, with adjusted
      rate ratio of 1.72 (95% CI 1.23-2.40; p = 0.001), for the most active men and
      vigorous activity was associated with a non-significant lower risk of colon
      cancer, the adjusted rate ratio being 0.72 (95% CI 0.47-1.11; p = 0.06).
      CONCLUSION: Generally, there were no, or only weakly, inverse associations
      between physical activity in leisure time and incidence of cancer, except for
      cancer of the ovary.

PMID- 16087487
TI  - The association of employment status and family status with health among women
      and men in four Nordic countries.
AB  - AIMS: The Nordic countries have relatively equal employment participation between
      men and women, but some differences between countries exist in labour market
      participation. The aim was to examine the association between employment status
      and health among women and men in Denmark, Finland, Norway, and Sweden, and
      analyse whether this association is modified by marital status and parental
      status. METHODS: The data come from nationally representative cross-sectional
      surveys carried out in Denmark (n = 2,209), Finland (n = 4,604), Norway (n =
      1,844) and Sweden (n = 5,360) in 1994-95. Women and men aged 25-49 were included.
      Employment status was categorized into full-time employed, part-time employed,
      unemployed, and housewives among women and into employed and unemployed among
      men. Health was measured by perceived health and limiting longstanding illness.
      Logistic regression analysis was used, adjusting for age and education. Marital
      status and parental status were analysed as modifying factors. RESULTS: The non
      employed were more likely to report perceived health as below good and limiting
      longstanding illness than the employed among both women and men. The association
      between employment status and perceived health remained unchanged when marital
      status and parental status were adjusted for among all men and Finnish women, but
      the association was slightly strengthened among Danish and Swedish women, with
      the housewives becoming more likely to report ill health than employed women. The
      association between employment status and limiting longstanding illness was
      slightly strengthened among women, and slightly weakened among Norwegian men when
      marital and parental status were adjusted for. CONCLUSIONS: Non-employment was
      associated with poorer health in all countries, although there are differences in
      the employment patterns between the countries. Among women marital status and
      parental status showed a modest or no influence on the association between
      employment status and health. Among men there was no such influence.

PMID- 16087488
TI  - "Struggling with life": narratives from women with signs of postpartum
      depression.
AB  - AIM: The aim of this study was to explore and describe how Swedish women with
      signs of postpartum depression two months postpartum experience the first months
      with their child. METHOD: A grounded theory approach was chosen. Twenty-two women
      who showed signs of depression, i.e. scored 10 or more on the Edinburgh Postnatal
      Depression Scale (EPDS), were interviewed at an average of 80 days after the
      delivery. RESULTS: The new mothers were struggling with life related to the self,
      the child, and the partner. They expressed feelings of loss of who they are, felt
      overwhelmed by the responsibility for the child, and were struggling with
      feelings of abandonment, worries, and breastfeeding problems. They often felt
      like "bad mothers" but they never blamed the child. Most mothers were reluctant
      to speak about their feelings and they assigned their depressed mood to personal
      weakness rather than illness. In relationship to the partner the mothers were
      struggling to keep their equality in the new situation and to get him involved in
      childcare. CONCLUSIONS: The findings suggest that depressed feelings postpartum
      may be explained in terms of losses and changes. However, postpartum depressive
      symptoms remain hidden and it is important to understand the complexity of
      postpartum depressive mood, described here as struggling with life related to
      three different dimensions: the self, the child, and the partner.

PMID- 16087489
TI  - Low socioeconomic status is associated with chronic musculoskeletal complaints
      among 46,901 adults in Norway.
AB  - AIMS: A study was undertaken to evaluate the relationship between socioeconomic
      status (SES) and chronic musculoskeletal complaints (MSC), and to determine how
      this relationship is influenced by change in SES. METHODS: Two consecutive public
      health surveys within the county of Nord-Trondelag, Norway, were conducted in
      1984-86 (HUNT-1) and 1995-97 (HUNT-2). Among 46,901 adults who participated in
      both surveys, 24,127 persons (51%) in HUNT-2 who reported MSC continuously for at
      least 3 months during the past year were defined as having chronic MSC.
      Prevalence of chronic MSC was estimated at nine anatomical sites using multiple
      logistic regression with odds ratio (OR) and 95% confidence interval (CI) as
      measures of association with SES. RESULTS: When defining SES by educational
      level, type of occupation, or income, low status was associated with increased
      prevalence of chronic MSC (age-adjusted analyses). The negative influence of low
      education or low occupation level was not eliminated by increasing the level of
      education or occupation from HUNT-1 to HUNT-2, in contrast with what was found
      for individuals with higher income level in HUNT-2 than in HUNT-1. The
      relationship with SES was more evident among individuals with musculoskeletal
      symptoms 15 days during the past month than among those with less than 15 days,
      evident at all nine different anatomical sites. The strongest relationship was
      found between low SES and prevalence of widespread chronic MSC. CONCLUSIONS:
      Individuals with low SES had higher prevalence of chronic MSC than those with
      high SES. Future studies should try to clarify whether chronic MSC are a cause or
      consequence of low SES.

PMID- 16087490
TI  - The impact of country of birth and time in Sweden on overweight and obesity: a
      population-based study.
AB  - AIMS: A study was undertaken to investigate the relationship between country of
      birth, time in Sweden, and overweight and obesity. METHODS: Approximately 4,000
      people aged 20-80 participated in a cross-sectional survey in 1994. The ethnic
      differences in overweight and obesity were analysed in a multivariate logistic
      regression analysis adjusting for age and education. The effect of number of
      years spent in Sweden on overweight and obesity was assessed for some of the
      ethnic groups compared with the Swedish-born group. RESULTS: Men from Yugoslavia
      and Arabic-speaking countries were overweight/obese (BMI 25.0-) and obese (BMI
      30.0-) to a significantly higher extent than men born in Sweden. Women born in
      Poland, Arabic-speaking countries, and all other countries were overweight/obese
      and obese to a significantly higher extent than women born in Sweden. Both Arabic
      men and women who had immigrated to Sweden in 1989 or earlier had an increased
      risk of overweight/obesity and obesity compared with the participants born in
      Sweden, while no increased risk was observed for the Arabic group that immigrated
      after 1989. CONCLUSIONS: There were significant differences in overweight and
      obesity between the country of birth groups. The findings follow the patterns of
      low leisure time physical activity among certain ethnic groups reported in a
      previous study, which has implications for public health measures directed to
      decrease differences in overweight and obesity by country of birth.

PMID- 16087491
TI  - Migration and smoking: an epidemiological study of Finnish twins in Sweden.
AB  - BACKGROUND: Male migrants from Finland to Sweden have been found to have a
      reduced risk of coronary heart disease after several years in Sweden. Changes in
      smoking habits may contribute to this reduced risk. AIMS: A study was undertaken
      to compare smoking habits in Finnish migrants to Sweden and subjects always
      living in Finland and to analyse whether the migration may have influenced
      smoking. METHODS: The study population consisted of same-sex twin pairs born in
      Finland younger than 76 years with at least one twin that had migrated to Sweden
      (n = 1,083 pairs). Smoking habits obtained by mailed questionnaire were compared
      in migration-discordant twin pairs to take into account early childhood and
      genetic factors. RESULTS: Immigrants and returnees with a history of smoking had
      predominantly started to smoke before the migration. Among women, immigrants to
      Sweden smoked more than never migrants in Finland, odds ratio (OR) 2.1 for
      current smokers (95% confidence interval CI 1.4-3.3) but this difference was
      already present before migration. In men there were essentially no differences in
      smoking prevalence between immigrants and never migrants but heavy smoking was
      less common among immigrants than among never migrant smokers, OR 0.5 (95% CI 0.2
      0.9) and migration was associated with a greater propensity to cease smoking.
      CONCLUSIONS: Migration from Finland to Sweden does not seem to have had a strong
      influence on smoking among migrants. A favourable trend in smoking habits after
      migration may in part have contributed to reduced mortality and incidence of
      coronary heart disease in male Finnish migrants after several years in Sweden.

PMID- 16087492
TI  - Implementation of functional assessment scales in geriatric practice: a
      feasibility study.
AB  - AIM: A study was undertaken to evaluate the feasibility of functional assessment
      scales regarding completion rate and ability to document functional changes in
      geriatric rehabilitation patients. METHODS: Five functional assessment scales
      were implemented, and used on admission and discharge as part of standard care.
      RESULTS: Of 2,812 patients, 90 patients (3.2%) had no scales administered, 2,330
      patients (82.9%) had between one and six scales administered and 392 (13.9%) had
      a complete data set (seven scales). The percentage of inpatients who were
      independent or almost independent in basic ADL functions improved from 30% to 60%
      during hospitalization; 53% had cognitive impairment, while 19% expressed
      depressive thoughts or depression on admission. CONCLUSION: Functional assessment
      scales were feasible in the clinical routine, gave important information on
      patients' functional status at baseline, and showed that patients improved their
      physical function considerably during hospitalization. Interdisciplinary teamwork
      and management affect the success of the implementation of assessment scales.

PMID- 16087493
TI  - Occurrence of violence and violence-related injuries among 12-18 year-old Finns.
AB  - AIMS: The aim of this study was to investigate the occurrence, nature, and
      severity of violence and violence-related injuries, and the occurrence of alcohol
      related violence among Finnish adolescents. METHODS: A 12-page questionnaire was
      mailed to a nationwide representative sample of 12-, 14-, 16-, and 18-year-olds
      (n = 10,883). The response rate was 75%. RESULTS: Of the 8,135 respondents, 7.9%
      (646) reported violence occurrence and 1.7% violence-related injury during the
      past month. The male-female ratio for violence occurrence was 1.9 (95% CI 1.6
      2.2) and for violence-related injury occurrence 0.8 (95% CI 0.6-1.2). Sixteen
      year-old girls reported the highest injury rate (23/1,000). Most typically, the
      violent persons were individuals known by the victim before the incident. Girls
      were significantly (p < 0.001) more often (43%) in a fight with, or assailed by,
      a family member than boys (8%). Although boys' violent actions were related to
      leisure-time activities (64%), violence rarely took place during sports
      activities. Alcohol-related violence increased with age. Some 13% of 14-year-olds
      reported being under the influence of alcohol at the time of violence. The
      corresponding figures for 16- and 18-year-olds were 41% and 62%, respectively.
      Moreover, alcohol was closely associated with violence-related injuries.
      CONCLUSIONS: Violence is common among Finnish adolescents. While violence does
      not always lead to injury, related injuries are an important cause of adolescent
      morbidity. Alcohol seems to be strongly associated with adolescent violence and
      related injuries.

PMID- 16087494
TI  - Sickness certificates as a basis for decisions regarding entitlement to sickness
      insurance benefits.
AB  - BACKGROUND: The sickness certificate is a major instrument for establishing
      contact and conveying information between two authorities that have a substantial
      impact on the life situation and work situation of the patients, as well as on
      the economic costs of the society. AIM: A study was undertaken to assess the
      quality of physicians' sickness certificates as a basis for social insurance
      officers' decisions regarding entitlement to sickness benefits. METHOD:
      Information on all 2,449 sickness certificates for sick-leave periods exceeding
      28 days' sick leave period received at the social insurance offices in one
      Swedish county during one week in 2002 was coded and analysed. RESULTS:
      Information provided in the certificates was often not sufficient to allow social
      insurance officers to determine eligibility for sickness benefits. Qualitative
      analyses of certificates from general practitioners (GPs) revealed that 21%
      contained ambiguous statements about the medical disorder, 30% were unclear
      regarding the assessment of functional capacity, and 22% required additional
      information on both those aspects. Sickness certificates issued by GPs and
      physicians under specialist training, as compared with other categories of
      physicians, more often provided essential data, for example concerning the
      patient's occupational tasks and type of employment. CONCLUSIONS: Physicians
      often fail to contribute required information concerning functional capacity and
      other important aspects when issuing sickness certificates. This limits the use
      of these documents as a basis for decisions regarding sickness insurance
      benefits. The practical consequences of incomplete certificates might be delayed
      payment of benefits and delayed initiation of return to work measures.

PMID- 16087495
TI  - The decline of smoking in northern Sweden.
AB  - For decades men in Sweden have smoked at far lower rates than those in comparable
      countries. Previous studies showed that snus use played a major role in low
      smoking rates among men in northern Sweden; daily smoking declined from 19% (95%
      CI 16-22%) in 1986 to 11% (CI 8.9-14%) in 1999. The prevalence of smoking among
      all men is now 9% (CI 7.0-11%) and only 3% (CI 0.1-5.4%) among men age 25-34
      years; the prevalence of exclusive snus use is 27% (CI 24-30%) and 34% (CI 27
      42%) respectively. Combined smoking and snus use, an unstable and transient
      category, was under 5% in all surveys and was 2.2% (CI 1.4-3.4%) by 2004. For the
      first time snus use is also associated with a decrease in smoking prevalence
      among women. These patterns of tobacco use have implications for all smoking
      dominated societies.

PMID- 16087496
TI  - Postural perturbation and muscular response following sudden release during
      symmetric squat and stoop lifting.
AB  - Squat and stoop lifting have been examined in some detail, but limited data exist
      regarding the sudden release of load during such lifting. Ten participants
      performed squat and stoop lifting trials with loads of 20, 40, 60 and 80N, and
      sudden release was randomly included in one of the lifting cycles. Postural
      perturbation was recorded via centre of pressure displacement using a force
      platform and the electromyographic response of trunk and lower limb muscles was
      recorded. Results indicated that irrespective of lifting posture, an 'ankle'
      response strategy to sudden release was elicited, where the anterior muscles of
      the lower limb contracted first, followed by the anterior trunk muscles,
      relaxation of the posterior trunk muscles and, finally, relaxation of the
      posterior lower limb muscles. The latency of muscles responding by contraction
      tended to decrease slightly with increasing load for both postures, while the
      latency of muscles responding by relaxation increased, resulting in increased
      trunk muscle co-contraction durations. The postural disturbance appeared to be
      greater for squat lifting than stoop lifting at the higher loads of 60 and 80N,
      as the centre of pressure moves significantly closer to the posterior limit of
      static stability (the line joining the heels).In terms of stability and muscular
      response, squat lifting may not be the most appropriate strategy if a sudden
      release of loads greater than approximately 50N is likely.

PMID- 16087497
TI  - Unobtrusive vehicle motion prediction cues reduced simulator sickness during
      passive travel in a driving simulator.
AB  - This study investigated cues that permit prediction of turns during passive
      movement through a virtual environment. Effects on simulator sickness (SS),
      presence and enjoyment were examined. Subjects were exposed to complex visual
      motion through a cartoon-like simulated environment in a driving simulator.
      Forward velocity remained constant and the motion path was the same across all
      experimental conditions. Using a within-subject design, we examined visual paths
      that provided different levels of cue salience - detailed, simplified and no cues
      - for the upcoming simulated vehicle motion. Following each trial, participants
      completed questionnaires on SS, presence and enjoyment. After all of the trials
      were completed, a debriefing determined participants' perceptions of vehicle
      motion attributes and their awareness of the prediction cues. The results showed
      that SS in the no-cue condition was significantly greater than that in the
      conditions that provided vehicle motion cues. Presence and enjoyment responses
      were not different across the conditions. No participants reported differences
      between prediction cue conditions or recognized that the vehicle motion followed
      the same path across trials. However, participants tended to report that the
      motion was smoother for the detailed-cue than the no-cue condition. Participants
      ranked turn predictability as higher in conditions with prediction cues. The
      results support the hypothesis that unobtrusive and unreported motion cues may
      alleviate SS in a virtual environment.

PMID- 16087498
TI  - 3D foot shape generation from 2D information.
AB  - Two methods to generate an individual 3D foot shape from 2D information are
      proposed. A standard foot shape was first generated and then scaled based on
      known 2D information. In the first method, the foot outline and the foot height
      were used, and in the second, the foot outline and the foot profile were used.
      The models were developed using 40 participants and then validated using a
      different set of 40 participants. Results show that each individual foot shape
      can be predicted within a mean absolute error of 1.36 mm for the left foot and
      1.37 mm for the right foot using the first method, and within a mean absolute
      error of 1.02 mm for the left foot and 1.02 mm for the right foot using the
      second method. The second method shows somewhat improved accuracy even though it
      requires two images. Both the methods are relatively cheaper than using a scanner
      to determine the 3D foot shape for custom footwear design.

PMID- 16087499
TI  - The effect of backpack load on the gait of normal adolescent girls.
AB  - Concerns regarding the effects of load carriage have led to recommendations that
      backpacks be limited to 10?-?15% of body weight, based on significant changes in
      physical performance. However, gait responses to backpack loads are not entirely
      consistent and there is a particular lack of data regarding load-bearing gait in
      adolescent females. Gait patterns of 22 normal adolescent girls were recorded at
      backpack loads of 0, 7.5, 10.0, 12.5 and 15.0% body weight. Temporal-distance,
      ground reaction force and joint kinematic, moment and power parameters were
      analysed by repeated measures ANOVA with factors of backpack load and side (left
      or right). Walking speed and cadence decreased significantly with increasing
      backpack load, while double support time increased. Kinematic changes were most
      marked at the proximal joints, with a decreased pelvic motion but a significant
      increase in the hip sagittal plane motion. Increased moments and power at the
      hip, knee and ankle showed increasing demand with backpack load. Parameters
      showed different responses to increasing load, and those that suggested a
      critical load indicated this to be approximately 10% body weight. While this may
      be due to a change in gait due to increased demand, further work is required to
      verify this and also to examine the cumulative effects of backpack load on the
      musculoskeletal system, which may be more appropriate in determining recommended
      load limits.

PMID- 16087500
TI  - The influence of occupation on lumbar sagittal motion and posture.
AB  - The aim of this study was to determine whether sheep shearers have clinically
      hypothesized adaptive postural and sagittal mobility parameters of the lumbar
      spine and pelvis. Sixty-four shearers and 64 non-shearers, matched by age and
      anthropometry and surveyed for present and previous low back pain, participated
      in a study to determine the effects of occupation on sagittal spinal motion and
      posture. Lumbar and hip mobility measurements were made with a geometric CAD
      analysis of lateral photographs using surface reflective markers. Sagittal range
      of motion demonstrated similar ranges of lumbar flexion between the two groups;
      however, there was a marked gain in hip flexion in the shearers as well as a
      marked loss of lumbar extension. The shearers also demonstrated a more lordotic
      lower lumbar curvature compensated by a flatter (less kyphotic) mid to lower
      thoracic region. Shearers appear to lose lumbar extension, gain hip flexion and
      develop an adaptive normal stance. This adaptation appears to be independent of
      previous or current back pain. Conversely, lumbar extension loss in non-shearers
      correlates with previous back injury. A stepwise linear regression of all
      participants indicated that the occupation is the predominant influence on motion
      and posture followed by age. The implications are one of structural adaptation in
      this occupational group that does not appear to be correlated with back pain.

PMID- 16087501
TI  - Complete recovery time after exhaustion in high-intensity work.
AB  - This study was aimed to investigate complete recovery time (CRT) after exhaustion
      in high-intensity work. Twenty-four subjects were divided into two groups based
      on the cardiorespiratory capability index, which was measured in a maximum
      capacity test. Each subject then performed two cycling tests (at 60% and 70%
      maximum working capacity). The subject continued cycling until exhaustion in each
      test and then sat recovering until he/she no longer felt fatigue or until the
      oxygen uptake (VO2) and heart rate (HR) returned to their baselines, whichever
      was longer. The results indicated that HR required the longest time to recover
      and, consequently, HR data were adopted to set the CRT. The CRT was significantly
      correlated with the cardiorespiratory capability index and the relative workload
      indices: RVO2 and RHR. The RVO2 was the average elevation in VO2 during work from
      the resting level as a percentage of maximum VO2 reserve. The RHR's definition
      was similar to that of RVO2. Based on the obtained CRT-prediction model, the CRT
      for a high-cardiorespiratory-capability person was 20.8, 22.1, 23.4, and 24.7 min
      at 50%, 60%, 70%, and 80% RHR levels, respectively. These suggested CRT values
      should be increased by 10 min for a low-cardiorespiratory-capability person.

PMID- 16087502
TI  - Good vibrations: do electrical therapeutic massagers work?
AB  - Health, leisure and beauty activities are increasing in popularity, with a
      particular emphasis on self-help and alternative health practices. One product
      type that has increased sales with this expansion is the hand-held electric
      massager. These are products that use vibration as a means of alleviating
      muscular strains and pains, as well as promoting relaxation. Paradoxically, these
      products are extremely popular as gifts, but are soon discarded. A multi
      disciplinary research team was commissioned by a British manufacturer of
      electrical consumer products to investigate user attitudes and perceptions of
      existing massagers, to identify areas of user dissatisfaction. The manufacturer
      was also concerned about a possible stigma attached to these products because of
      an association with sex aids. This paper provides an account of the perceptions
      of both consumers and therapists regarding the use of these products. Identifying
      the differences between the perceptions of consumers and therapists should help
      provide a basis for effective integration of user needs, manufacturer
      requirements, designers' skills and sound therapeutic practice. The results
      provide insight to support the development of more effective hand-held massagers.

PMID- 16087503
TI  - Identifying predictors of comfort and discomfort in using hand tools.
AB  - The aim of the study was to identify predictors of comfort and discomfort in
      using hand tools. For this purpose, the comfort questionnaire for hand tools
      (CQH) was developed based on the results of a previous study. In the current
      study, four screwdrivers were evaluated on comfort (expected comfort at first
      sight and comfort after short time use) using the CQH and discomfort (local
      perceived discomfort). The results showed that expected comfort at first sight
      was predicted by aesthetics. Additionally, functionality and physical
      interaction, and adverse body effects were the major predictors of overall
      comfort after short time use. Discomfort was predicted by adverse body effects
      only. It is concluded that comfort and discomfort in using hand tools have partly
      the same underlying factors: discomfort feelings also affect the comfort
      experience.

PMID- 16087504
TI  - Forearm torque strengths and discomfort profiles in pronation and supination.
AB  - This experiment investigated maximum forearm pronation and supination torques and
      forearm discomfort, for intermittent torque exertions in supine and prone forearm
      angles for the right arm. Twenty-two subjects participated in the study that
      comprised two parts, the first of which involved measurement of maximum forearm
      torque in both twisting directions at five forearm angles including neutral. This
      was followed by endurance tests at 50% maximum voluntary contraction (MVC) in
      both directions. The second part of the study involved subjects performing 5-min
      duration of intermittent isometric torque exercises at 20% MVC in both directions
      at 11 forearm angles. Regression equations were developed that accurately predict
      torques as a function of forearm angle expressed as a percentage of maximum
      motion. Analysis of the discomfort data for the intermittent isometric torque
      exertions indicated that both forearm angle and twisting direction significantly
      affected forearm discomfort (p < 0.001). A significant two-way interaction (p <
      0.01) was identified between forearm angle and direction for supine forearm
      angles only. The results provide important strength and discomfort models for the
      design of tasks involving static or repetitive forearm twisting. Such tasks have
      a strong association with forearm injuries including lateral and medial
      epicondylitis. These results provide needed data on the risk factors associated
      with these injuries so they can be prevented.

PMID- 16087512
TI  - British Fertility Society the University of Sheffield 15-17 April 1998.

PMID- 16087514
TI  - Video review.

PMID- 16087505
TI  - Forward/up directional incompatibilities during cursor placement within graphical
      user interfaces.
AB  - Within graphical user interfaces, an indirect relationship between display and
      control may lead to directional incompatibilities when a forward mouse movement
      codes upward cursor motions. However, this should not occur for left/right
      movements or direct cursor controllers (e.g. touch sensitive screens). In a four
      choice reaction time task, 12 participants performed movements from a central
      start location to a target situated at one of four cardinal points (top, bottom,
      left, right). A 2 x 2 x 2 design varied directness of controller (moving cursor
      on computer screen or pen on graphics tablet), compatibility of orientation of
      cursor controller with screen (horizontal or vertical) and axis of desired cursor
      motion (left/right or up/down). Incompatibility between orientation of controller
      and motion of cursor did not affect response latencies, possibly because both
      forward and upward movements are away from the midline and go up the visual
      field. However, directional incompatibilities between display and controller led
      to slower movement with prolonged accelerative phases. Indirect relationships
      between display and control led to less efficient movements with prolonged
      decelerative phases and a tendency to undershoot movements along the bottom/top
      axis. More direct cursor control devices, such as touch sensitive screens, should
      enhance the efficiency of aspects of cursor trajectories.

PMID- 16087515
TI  - British Fertility Society Workshop British Andrology Society Annual Meeting
      Association of Clinical Embryologists Workshop University of Birmingham 13 and 14
      November 1998.

PMID- 16087516
TI  - Recommendations for good practice - Welfare of the child British Fertility
      Society 1999.

PMID- 16087518
TI  - British Fertility Society Annual Conference Newcastle Upon Tyne 14-16 April 1999.

PMID- 16087519
TI  - Meeting report: World Congress on Practical Infertility Management(*).

PMID- 16087520
TI  - Instructions for authors of primary papers.

PMID- 16087522
TI  - Invited commentaries on the Royal College of Obstetricians and Gynaecologists'
      guidelines on the management of infertility in tertiary care(1).

PMID- 16087521
TI  - British Fertility Society and Association of Clinical Embryologists Joint Winter
      Meeting Bath 11-12 January 2000.

PMID- 16087523
TI  - Rationing fertility services in the NHS: A policy statement.

PMID- 16087524
TI  - Accreditation standards and guidelines for IVF laboratories.

PMID- 16087525
TI  - British Andrology Society British Fertility Society Society for the Study of
      Fertility Fertility 2000 Edinburgh 31 July-2 August 2000.

PMID- 16087526
TI  - Abstracts of invited contributions.

PMID- 16087527
TI  - Fertility 2000: session reports. Embryology 1.

PMID- 16087528
TI  - Response to the BFS recommendations for good practice on the screening of egg and
      embryo donors.

PMID- 16087531
TI  - Nursing the clinic and managing emotions in a fertility unit: findings from an
      ethnographic study by Helen Allan (Human Fertility 4 18-23).

PMID- 16087550
TI  - From research to clinical practice: considerations in moving research into
      people's hands. Personal reflections that may be useful to others.
AB  - It may take many years for published clinical research findings to be found,
      understood, adopted and applied in practice. In recognition of this delay, many
      jurisdictions and agencies are now promoting a stronger link between research and
      its dissemination in useable forms that will enable practitioners to access,
      understand and use new ideas. The purpose of this paper, first presented as a
      keynote address at the 15th Annual Meeting of the European Academy of Childhood
      Disability in Oslo in October 2003, is to share experiences of the author and his
      colleagues at a childhood disability system-linked research centre in Ontario,
      Canada. The lessons learned include the value of striving to describe one's
      findings in plain language; writing study reports for parents and children who
      are involved in research studies; using multiple methods to disseminate one's
      work; and making explicit the potential importance and applicability of the
      findings to readers of the work. Engaging end users at many stages of the
      development and field testing of one's work will enhance buy-in and lend added
      credibility to the work, as well as influencing content and process as the
      research unfolds. The result is likely to be greater recognition of 'familiar'
      aspects of the research and the adoption of relevant findings.

PMID- 16087551
TI  - Intrathecal baclofen in the management of spasticity due to cerebral palsy.
AB  - Intrathecal baclofen is a cornerstone in the treatment of spasticity in children.
      However, further research is required to set criteria for treatment. This paper
      offers insight into the national act on baclofen and the experience at the
      Nottingham University Hospital.

PMID- 16087552
TI  - Hector Landouzy on facial paralysis in newborn children: the case studies of a
      19th-century French hospital physician.
AB  - Marc-Hector Landouzy (1812-1864) was one of the first to describe facial
      paralysis in newborn, through a series of case studies. By examining these four
      cases in the context of Landouzy's life, publications and professional
      circumstances, this study shows how case studies were an important part of the
      scientific revolution within medicine in the 19th century. Landouzy, soon
      followed by others, used the growing clinical populations of Parisian hospitals,
      patho-anatomy and cutting-edge physiologic techniques to help describe a
      previously ignored disease among newborns. His case studies, in particular, are a
      valuable example of the emerging interest in children as a clinical population
      and of early interest in child neurology.

PMID- 16087553
TI  - Behavioural treatment of non-compliance in adolescents with newly acquired spinal
      cord injuries.
AB  - PURPOSE: To demonstrate the efficacy of using differential reinforcement to treat
      non-compliance in adolescents with spinal cord injury. METHOD: A case series
      design was used to examine three adolescents (aged 14-16 years) with tetraplegia
      who received multi-disciplinary rehabilitation treatment and a behavioural
      contract programme during an in-patient hospital admission. Assessment included
      collecting data on each patient's weekly percentage of compliance with all
      rehabilitation goals, weekly percentage of negative affect observed in therapy
      sessions and scores on a measure of mobility in physical therapy. RESULTS:
      Compliance with rehabilitation demands improved from a baseline of 20-65% to 80%
      or greater after the patients received differential reinforcement for
      participating in the rehabilitation regimen. Patients exhibited less anger,
      sadness and frustration during therapy sessions once contracts were started.
      CONCLUSIONS: The adolescents demonstrated greater compliance after the
      implementation of a behavioural contract. Future studies should identify the
      specific variables that affect psychological adjustment and predict 'readiness'
      to participate in rehabilitation.

PMID- 16087554
TI  - Brace treatment during pubertal growth spurt in girls with idiopathic scoliosis
      (IS): a prospective trial comparing two different concepts.
AB  - STUDY DESIGN: Prospective comparison of the survival rates of two different
      bracing concepts with respect to curve progression and duration of treatment
      during pubertal growth spurt in two cohorts of patients followed up
      prospectively. OBJECTIVES: To determine whether the results obtained by the use
      of a soft brace (SpineCor) is comparable to the results of the Cheneau derived
      TLSO during pubertal growth spurt. BACKGROUND DATA: In recent peer reviewed
      literature, the SpineCor is described as an effective method of treatment for
      patients with scoliosis. However, until now, no controlled study has been
      presented comparing the results obtained with this soft brace to a sample treated
      with other bracing concepts proven effective. METHODS: Twelve patients with Cobb
      angles between 16-32 degrees during pubertal growth spurt are presented as a case
      series treated with the SpineCor. The survival rate of this sample is described
      and compared to a matched group of patients treated with the Cheneau brace of the
      same age group. All girls treated in both studies were pre-menarchial with the
      first clinical signs of maturation (Tanner 1-3). RESULTS: During the pubertal
      growth spurt, most of the patients (11/12) with SpineCor progressed clinicly and
      radiologicly as well (at least 5 degrees ). Progression could be stopped changing
      SpineCor to the Cheneau brace in most of the samples described (7/10). The
      avarage Cobb angle at the start of treatment with the SpineCor was 21.3 degrees ,
      after an avarage observation time of 21.5 months, 31 degrees. The control sample,
      primarily treated with the Cheneau brace (n=15), showed at average no
      progression. Cobb angle at the start of treatment was 33.7 degrees and after the
      observation time of 37 months, 33.9 degrees . Radiological improvements can be
      reported for some of the cases (3/15) as well as progressions (3/15). At 24
      months of treatment time, 73% of the patients with a Cheneau brace and 33% of the
      patients with the SpineCor where still under treatment with their original
      bracing concept, at 42 month follow-up time 80% of the patients with Cheneau
      braces and 8% of the patients with the SpineCor survived with respect to
      curvature progression. The differences of the proportions statisticly where
      highly significant. CONCLUSIONS: The SpineCor does not change natural history of
      idiopathic scoliosis during the pubertal growth spurt. The use of the Cheneau
      brace seems to do so. Oncoming studies with the aim to test the efficiency of
      braces should be based on samples at immediate risk for progression (only girls
      with first signs of maturation but pre-menarchial).

PMID- 16087555
TI  - GMFM 1 year after continuous intrathecal baclofen infusion.
AB  - The purpose of this study was to assess whether there is an improvement in motor
      function in persons with cerebral palsy (CP) who have had a reduction of muscle
      tone by continuous intrathecal baclofen infusion. This was a prospective, open
      label, non-blinded case series without a control group, conducted at multiple
      centres. There were 31 subjects, aged 4-29 years. All had a pre-treatment mean
      lower extremity Ashworth scores of >or= 3 and a significant reduction in tone
      after a bolus injection of intrathecal baclofen (ITB) and received an implanted
      pump for continuous delivery of ITB. Motor function was assessed by the Gross
      Motor Function Measure (GMFM) prior to and 1 year following pump implantation.
      Significant improvement (p < 0.05) in mean GMFM scores was seen in subjects < 8
      years (mean change 4.1) and in those from 8-18 years (mean change 3.7) and in
      subjects with CP Classes 2 and 5 (mean changes 6.2 and 2.9). There was a
      statistically significant decrease (p < 0.05) in Ashworth scores in CP classes 2
      5. Subjects or their caregivers that completed a survey about perceived changes
      stated that motor control, positioning and endurance improved.

PMID- 16087556
TI  - Tracheostomy speaking valves for children: tolerance and clinical benefits.
AB  - INTRODUCTION: Use of a tracheostomy speaking valve allows the expiratory flow of
      air to exit over the vocal folds promoting phonation. The purpose of this
      retrospective review was to determine: (1) what percentage of trial candidates
      tolerated a speaking valve; (2) whether candidates achieved phonation with a
      valve; and (3) which secondary benefits (coughing ability, secretion management,
      swallowing/feeding and oxygenation) could be clinically observed. METHODS: Twelve
      cases of children and youth (ages 8 months to 21 years) evaluated for a
      tracheostomy speaking valve at an inpatient rehabilitation hospital were
      reviewed. A speech-language pathologist and respiratory therapist evaluated the
      children for valve tolerance and candidacy for ongoing use. Clinical observations
      were used to determine phonation ability and to examine potential secondary
      benefits. RESULTS: All 10 subjects who tolerated the valve achieved phonation.
      Vocalizations included audible crying, non-specific vocalizations, word
      approximations, single words and short phrases. Minimal-to-no improvement was
      noted for coughing, secretion management, swallowing and oxygenation with
      clinical assessment. DISCUSSION: With supervision and training, speaking valves
      can enhance communication options for children and youth with tracheostomies and
      oxygen and ventilator dependence. Physiological and functional secondary benefits
      were observed but were more difficult to assess.

PMID- 16087557
TI  - Long-term psychological distress in parents of child survivors of severe
      meningococcal disease.
AB  - OBJECTIVE: To study psychological distress in parents of child survivors of
      Severe Meningococcal Disease (SMD) after discharge of their child from the
      Paediatric Intensive Care Unit (PICU). METHODS: This study approached parents of
      child survivors of SMD treated on the PICU between 1993-2001. Five cross
      sectional groups were created for mothers and fathers separately. The five groups
      differed from each other by the period after discharge they entered the project
      (ranging from 3 months to 7 years after discharge). For research purposes,
      mothers and fathers (n = 192) individually completed the Goldberg General Health
      Questionnaire-30 (GHQ), measuring their level of psychological distress.
      STATISTICS: Mean group scores were examined and a one-way-analysis of variance
      (ANOVA) performed to study differences between groups for mothers and fathers
      separately. In addition, percentages of parents with GHQ scores above cut-off
      were calculated and it was determined whether it differed from norm data.
      RESULTS: Data reveal that both mothers and fathers experience high mean levels of
      psychological distress after discharge, showing no significant differences in
      group means over time. High percentages of parents experience psychological
      distress after discharge, if compared with the normal population. CONCLUSIONS:
      Parents of child survivors of SMD experience profound and prolonged psychological
      distress after discharge. Future interventions should focus on follow-up care for
      this population to help them re-adjust after this stressful event.

PMID- 16087558
TI  - Concurrent validity of the Neurobehavioural Assessment for Pre-term Infants
      (NAPI) at term age.
AB  - BACKGROUND: Accurate measurement of neonatal neurological integrity is critical
      for early identification of pre-term and full-term infants at-risk for
      developmental disability. The Neurobehavioural Assessment for Pre-term Infants
      (NAPI) was developed to measure the progression of neurobehavioural development
      in pre-term infants born between 32 weeks post-conceptional age (PCA) and term.
      This instrument has many unique advantages; however, criterion validity is
      unknown and results are subsequently difficult to interpret. OBJECTIVES: This
      study examined the concurrent validity of the NAPI against a criterion
      instrument, the Einstein Neonatal Neurobehavioural Assessment Scale (ENNAS),
      which measures similar constructs and has demonstrated excellent reliability and
      validity. METHODS: A sample of 41 pre-term and full-term infants (40 +/- 2 weeks)
      was assessed with the NAPI and ENNAS on the same day. RESULTS: The findings
      demonstrated that correlations between similar NAPI clusters and ENNAS clusters
      ranged from 0.35-0.65 and correlations between many similar individual NAPI and
      ENNAS items ranged from 0.40-0.60. Two NAPI clusters also discriminated between
      normal, abnormal and suspect performance on the ENNAS. CONCLUSION: The NAPI has
      many unique advantages as a tool. It examines neonates serially, has established
      weekly normative data and requires minimal infant handling. This study provides
      new validation of the NAPI instrument.

PMID- 16087559
TI  - The therapeutic values of plants.

PMID- 16087561
TI  - Urethral sphincters response to cavernosus muscles stimulation with
      identification of cavernoso-urethral reflex.
AB  - The functional activity of the urethral sphincters during cavernosus muscles'
      contraction at coitus has been poorly addressed in the literature. We
      investigated the hypothesis that cavernosus muscles' contraction affects reflex
      contraction of the urethral sphincters to guard against semen reflux into the
      urinary bladder or urine leakage from the bladder during orgasm and ejaculation.
      The electromyographic (EMG) response of the external (EUS) and internal (IUS)
      urethral sphincters to ischio- (ICM) and bulbo- (BCM) cavernosus muscle
      stimulation was studied in 15 healthy volunteers (9 men, 6 women, age 39.3 +/-
      8.2 SD years). An electrode was applied to each of ICM and BCM (stimulating
      electrodes) and the 2 urethral sphincters (recording electrodes). The test was
      repeated after individual anesthetization of the urethral sphincters and the 2
      cavernosus muscles, and after using saline instead of lidocaine. Upon stimulation
      of each of the 2 cavernosus muscles, the EUS and IUS recorded increased EMG
      activity. Repeated cavernosus muscles' stimulation evoked the urethral
      sphincteric response without fatigue. The urethral sphincters did not respond to
      stimulation of the anesthetized cavernosus muscles nor did the anesthetized
      urethral sphincters respond to cavernosus muscle stimulation. Saline infiltration
      instead of lidocaine did not affect the urethral sphincteric response to
      cavernosal muscle stimulation. Results were reproducible. Cavernosus muscles'
      contraction is suggested to effect EUS and IUS contraction. This action seems to
      be reflex and mediated through the 'cavernoso-urethral reflex.' Urethral
      sphincters contraction upon cavernosus muscles contraction during sexual
      intercourse presumably prevents urine leak from the urinary bladder to urethra,
      prevents retrograde ejaculation, and propels ejaculate from the posterior to the
      penile urethra. The cavernoso-urethral reflex can act a diagnostic tool in the
      investigations of patients with ejaculatory disorders.

PMID- 16087562
TI  - Identification of c-kit-positive cells in the human prostate: the interstitial
      cells of Cajal.
AB  - The prostate exhibits electric activity in the form of slow waves (SWs) and
      action potentials (APs). As the interstitial cells of Cajal (ICCs) are considered
      the pacemaker cells which generate the electric waves, we investigated the
      hypothesis that the prostate contains ICC. Prostatic biopsies were obtained from
      15 healthy volunteers (mean age 36 +/- 3.8 SD years). They were subjected to c
      kit immunohistochemistry. Controls for the specificity of the antisera consisted
      of tissue incubated with normal rabbit serum substituted for the primary
      antiserum. C-kit-positive cells were identified as fusiform with dendritic
      processes. The cytoplasm was granular and the nucleus large and oval. Mast cells,
      also c-kit-positive, were round and lacked the dendritic processes.
      Immunoreactivity was absent in the negative controls. There were cells in the
      prostate with morphological and immunological phenotypes similar to ICCs of the
      gut. We predict an abnormal distribution of these cells in prostatic diseases.
      The study of the integrity of these cells may prove to be a useful investigative
      tool in the diagnosis of prostatic diseases and in the planning of an appropriate
      treatment.

PMID- 16087563
TI  - Individual cryopreservation with dimethyl sulfoxide and polyvinylpyrrolidone of
      ejaculates and pooled semen of three avian species.
AB  - Artificial insemination (AI) has been used for avian reproduction due to the
      discovery of cryoprotectants extending its usefulness both in production of
      domestic fowl and conservation of wild species. The goal of this study was to
      assess the effect on domestic and wild fowl pooled semen and individual ejaculate
      cryopreservation with dimethyl sulfoxide (DMSO) and polyvinylpyrrolidone (PVP).
      Twenty ejaculates and twenty samples of pooled semen of roosters, pheasants and
      hawks were frozen in media containing DMSO or PVP. DMSO and PVP cryopreservation
      are equally effective both for ejaculates and pooled semen. Even PVP is a good
      alternative since no significant difference was found when compared to DMSO. The
      fertilizing capacity of fresh and cryopreserved pooled semen was analyzed through
      AI of hens and female pheasants. Similar fertility rates using DMSO, PVP or
      frozen-thawed samples demonstrated that reproduction is possible through the use
      of cryopreserved semen. In the case of female pheasants, the same values were
      obtained with both cryopreserved and fresh semen.

PMID- 16087564
TI  - STD/HIV association: effects on semen characteristics.
AB  - A cross-sectional study was conducted on 83 fertile/infertile men to investigate
      the association between STDs and HIV and their effects on semen characteristics
      and seminal leucocytes. HIV antibodies in semen, andrological parameters and
      seminal leucocytes were analyzed. Of the 83 subjects, 36 were HIV+ and 47 were
      HIV- . Only 9 out of 36 HIV+ men and 25 out of 47 HIV- men had no history of STD.
      The most common type of STD was gonorrhea (65%) and 60% of those who had
      gonorrhea were HIV+ . HIV+ men had low sperm motility (p < 0.02). HIV+ men with a
      history of STD had leucocytospermia compared to HIV- men irrespective of history
      of STD (p < 0.001). Leucocytospermia was prevalent in HIV+ men even with no
      history of STD (p < 0.05). Non-ulcerative STDs was a risk factor for HIV
      infection. There was a significant association between HIV- and no history of
      STD. Impaired sperm motility in HIV+ men may be mediated by activated seminal
      leucocytes, which could induce oxidative stress on sperm. Leucocytospermia may be
      a reliable indicator of HIV+ .

PMID- 16087565
TI  - Giant seminal vesicle cyst resembling megaureter with hydronephrosis.
AB  - Seminal vesicle cysts combined with ipsilateral renal agenesis is a rare
      congenital anomaly. We report an extreme case whose image resembles megaureter
      and hydronephrosis. A standard nephrectomy was performed and spermatozoa with
      flattened, cuboidal, and pseudostratified epithelium was found microscopically.
      The diagnosis of seminal vesicle cyst was confirmed.

PMID- 16087567
TI  - Is there a relationship between cell phone use and semen quality?
AB  - This study was conducted to determine a possible relationship between regular
      cell phone use and different human semen attributes. The history-taking of men in
      our university clinic was supplemented with questions concerning cell phone use
      habits, including possession, daily standby position and daily transmission
      times. Semen analyses were performed by conventional methods. Statistics were
      calculated with SPSS statistical software. A total of 371 were included in the
      study. The duration of possession and the daily transmission time correlated
      negatively with the proportion of rapid progressive motile sperm (r = -0.12 and r
      = -0.19, respectively), and positively with the proportion of slow progressive
      motile sperm (r = 0.12 and r = 0.28, respectively). The low and high transmitter
      groups also differed in the proportion of rapid progressive motile sperm (48.7%
      vs. 40.6%). The prolonged use of cell phones may have negative effects on the
      sperm motility characteristics.

PMID- 16087566
TI  - Single UV excitation of Hoechst 33342 and propidium iodide for viability
      assessment of rhesus monkey spermatozoa using flow cytometry.
AB  - Many fluorescent probes excited by visible light have been used to assess sperm
      quality by flow cytometry. Developing a viability evaluation method using UV
      excited stains would be useful for multiparameter analysis of sperm function.
      This investigation was conducted to determine the efficacy of Hoechst 33342
      (H342) and propidium iodide (PI) dual staining for evaluating rhesus monkey sperm
      viability through use of flow cytometry and excited by a single UV laser. The
      results showed that the live cells stained only with H342 strongly correlated
      with expected sperm viability, and flow cytometric analyses were highly
      correlated with fluorescence microscopic observation. Using H342/PI/SYBR-14
      triple staining method, it was found that the live/dead sperm distributions were
      completely concordant in both H342/PI and SYBR-14/PI assays. In addition, this
      dual staining was extended with fluorescein isothiocyanate-conjugated peanut
      agglutinin (FITC-PNA) to simultaneously analyze viability and acrosome integrity
      of sperm cryopreserved using two different extenders, TTE and TEST, and indicated
      that TTE offered better preservation of plasma and acrosome integrity than TEST.
      Therefore, the H342/PI dual staining provides an accurate technique for
      evaluating viability of rhesus monkey sperm and should be valuable for
      multiparameter flow cytometric analysis of sperm function.

PMID- 16087568
TI  - Immunohistochemical, histological and ultrastructural evaluation of the effects
      of leptin on testes in mice.
AB  - This study was undertaken to examine the effects of leptin on testes in mice. For
      this purpose, 12 male mice were divided into two groups. Animals in Group I were
      designated as control. Mice in Group II were injected daily with leptin for 5
      days. All animals were decapitated at the end of the experiment. The testes were
      removed and weighed out. Testicular tissue specimens were processed for light and
      electron microscopic examination and semi-quantitative evaluation of
      immunohistochemical testosterone staining. Intensity of immunostaining was
      determined on a scale between 0 (no staining) and 5 (heavy staining). For
      morphometric comparison, diameters of seminiferous tubules from each group were
      measured. In the leptin injected group, testicular weights and diameters of
      seminiferous tubules were significantly increased in comparison to control
      values. In light microscopic examination, an increase in secretory granules in
      the cytoplasm of Leydig cells was observed after leptin treatment. In the same
      group, distinct changes indicative of increased cell activation were seen in the
      ultrastructure of Leydig cells. Amount of mitochondria, lysosomes and cytoplasmic
      secretory granules were increased. Furthermore, an increase in extensiveness of
      rough endoplasmic reticulum was noted in this group. Immunohistochemical
      testosterone staining of the cytoplasm of Leydig cells was heavy (5+) in the
      leptin treated mice compared to mild score (2+) in the control mice.
      Additionally, heavy immunostaining of testosterone was also observed in the
      interstitial space after injection of leptin. The present findings indicate that
      testicular functions and synthesis of testosterone increase after administration
      of leptin.

PMID- 16087569
TI  - Malignant tumor of testis imitating epididymo-orchitis.
AB  - From April 1994 to November 2004, a total of 65 patients with malignant
      testicular tumors underwent surgical interventions in our hospital. Clinical
      presentations and imaging findings led to quiet accurate preoperative diagnosis
      of malignant tumor, except for one case, a 29-year-old male, presenting with
      episodes of painful swelling in the right scrotum. All the findings including
      color duplex ultrasonography (US) and scintigraphy were considered as right
      epididymo-orchitis. Unfortunately, the patient presented with metastatic
      lymphadenopathy of the neck from mixed germ cell tumor of the testis 2 months
      later. Close follow-up for patients with suspected epididymo-orchitis is very
      important.

PMID- 16087570
TI  - Effect of race on fine particle deposition for oral and nasal breathing.
AB  - Nasal efficiency for removing fine particles from inhaled air may be affected by
      variations in nasal structure associated with race. In 11 African American and 11
      Caucasian adults (age 18-31 yr) we measured the fractional deposition (DF) of
      fine particles (1 and 2 mum mass median aerodynamic diameter) (MMAD) for oral and
      nasal breathing using individual breathing patterns previously measured by
      respiratory inductance plethysmography during a graded exercise protocol. DF for
      both nasal and mouth breathing was measured separately by laser photometry at the
      same tidal volume and breathing rate for resting and light exercise (20% of
      maximum work load) conditions. From these DF measures, nasal deposition
      efficiency (NDE) was calculated for each condition. For light exercise
      conditions, NDE for both 1- and 2-microm particles was less in African Americans
      versus Caucasians, 0.15 +/- 0.07 (SD) versus 0.24 +/- 0.11 for 1-microm particles
      (p = .03), and 0.29 +/- 0.13 versus 0.44 +/- 0.11 for 2-microm particles (p =
      .006). The racial differences in NDE were associated with racial differences in
      nasal resistance and nostril shape. These race-dependent nasal efficiencies are
      dosimetric factors that should be considered in modeling and assessing
      particulate dose from human exposure to air pollutants.

PMID- 16087571
TI  - The effect of coarse ambient particulate matter on first, second, and overall
      hospital admissions for respiratory disease among the elderly.
AB  - The objective of this article is to examine differences in the effect of ambient
      particulate matter on first, second, and overall hospital admissions for
      respiratory disease among the elderly. We studied 8989 adults 65 yr of age or
      older living in the greater Vancouver area who were admitted to hospital for any
      acute respiratory disease (ICD-9 codes 460-519) between June 1, 1995, and March
      31, 1999. Time-series analysis was used to evaluate the association between
      respiratory admissions and daily measures of particulate matter (PM10, PM2.5, and
      PM10 - 2.5) in urban air, after adjustment for gaseous copollutants (CO, O3, NO2,
      and SO2) and meteorological variables. Repeated admissions for respiratory
      disease were common among the elderly. Approximately 30% of the subjects were
      readmitted to hospital after the first admission; 9% had more than 2 admissions
      for respiratory disease during the 4-yr study period. PM10 - 2.5 was
      significantly associated with the second and overall admissions for respiratory
      disease, but not with the first admission. The adjusted relative risks for an
      increment of 4.2 microg/m(3) in -day average PM10 - 2.5 concentrations were 1.03
      (95% confidence interval: 0.98-1.09) for the first admission, 1.22 (1.10-1.36)
      for the second admission, and 1.06 (1.02, 1.11) for overall admissions. There was
      no significant association between PM2.5 and hospital admissions for respiratory
      disease among the elderly. Our data suggest that (1) people with a history of
      respiratory admissions are at a higher risk of respiratory disease in relation to
      particulate air pollution in urban areas, (2) analyses based on overall rather
      than repeated hospital admissions lead to lower estimates of the risk of
      respiratory disease associated with particulate air pollution, and (3) PM10 - 2.5
      has a larger effect on respiratory admissions than PM2.5.

PMID- 16087572
TI  - Responses to subchronic inhalation of low concentrations of diesel exhaust and
      hardwood smoke measured in rat bronchoalveolar lavage fluid.
AB  - Air pollution exposure is associated with adverse health effects, but the causal
      components and mechanisms are unclear. We compared effects of daily exposure for
      6 mo to diesel exhaust (DE) or hardwood smoke (HWS) at 4 concentrations between
      30 and 1000 microg/(3) of total particulate matter, or filtered air, in male and
      female rats. Lung lavage fluid was assayed for toxicity indicators, cytokines,
      and glutathione. Statistical analyses included pairwise comparisons with control
      and exposure-related trends, modeled using techniques that facilitated evaluation
      of nonlinear exposure effects. Lactate dehydrogenase increased with exposure
      concentration in DE-exposed females, but in other groups, low exposure
      concentrations caused increases while higher concentrations had less effect.
      Total protein in the HWS-exposed males and females followed similar patterns.
      Alkaline phosphatase increased in DE-exposed females, but decreased in HWS
      exposed males and females. Beta-Glucuronidase decreased in HWS- and DE-exposed
      males, but HWS-exposed females showed decreases at low exposure concentrations
      and weak increases at higher exposure concentrations. Macrophage inflammatory
      protein-2 decreased in HWS-exposed males and females and DE-exposed females.
      Tumor necrosis factor-alpha levels decreased in DE-exposed females and males, but
      HWS-exposed males showed small increases. DE did not affect total glutathione in
      either gender, but HWS decreased glutathione in females, while in males,
      increases at low exposure concentrations but not at higher exposure levels were
      observed. Thus, these two combustion emissions differentially affect lung
      responses, with gender affecting response patterns. Furthermore, effects may be
      nonmonotonic functions of exposure levels, with maximal responses in
      environmentally or occupationally relevant exposure ranges.

PMID- 16087573
TI  - Acute functional enhancement of circulatory neutrophils after intratracheal
      instillation with diesel exhaust particles in rats.
AB  - We have previously demonstrated that intratracheal instillation (IT) with diesel
      exhaust particles (DEP) exacerbates myocardial ischemia/reperfusion-induced
      arrhythmia in rats. Since activated neutrophils play a pivotal role in
      ischemia/reperfusion arrhythmia, in the present study we investigated the effects
      of DEP on peripheral neutrophil count and on the oxyradical production (ORP) of
      neutrophils in rats. We also determined the production of cytokines for better
      understanding of the relationship between pulmonary inflammation and neutrophil
      function. Instillation with 5 mg DEP elevated circulatory neutrophil counts (CNC)
      at 12 and 24 h post-instillation to levels approximately 2.1- and 2.3-fold those
      in the vehicle-treated animals, respectively. On the other hand, 1-mg DEP caused
      an approximately 0.4-fold increase in CNC at 6 h. 12-O-Tetradecanoylphorbol 13
      acetate-induced ORP in the isolated neutrophil was enhanced at 12 and 24 h after
      instillation with 5 mg DEP. Cytokine-induced neutrophil chemoattractant-1 (CINC
      1), tumor necrosis factor-alpha (TNFalpha) and macrophage inflammatory protein-2
      (MIP-2) levels were increased in the bronchoalveolar lavage fluid (BALF)
      collected from animals that received 5 mg DEP. In serum, a marked elevation of
      CINC-1 and a slight elevation of MIP-2 were also observed, while TNFalpha was not
      detected. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was detected
      in neither BALF nor serum for 24 h after the instillation. These results suggest
      that IT instillation of DEP enhances systemic oxidative stress by increasing
      neutrophil count and ORP in the acute period.

PMID- 16087574
TI  - Effects of microbial cocultivation on inflammatory and cytotoxic potential of
      spores.
AB  - Microbial growth on moisture-damaged building materials is commonly associated
      with adverse health effects in the occupants. In moisture damage situations, the
      environmental conditions as well as the dominant microbial species will vary,
      leading to a diversity of microbes and continual changes in the different
      microbial populations. Currently, very little is known about the effects of
      microbial cocultures on the potential harmfulness of the microbial population. In
      this study we have investigated the effects of cocultivation of certain indoor
      air microbes on the inflammatory and cytotoxic potential of their spores. We grew
      various microbial combinations made from strains of Streptomyces californicus,
      Stachybotrys chartarum, Aspergillus versicolor, and Penicillium spinulosum on
      wetted plasterboard. After 5 or 10 wk of growth, the spores were collected from
      the plasterboards, mouse RAW264.7 macrophages were exposed to the spores, and
      after 24 h the induced inflammatory and cytotoxic responses were analyzed. Among
      all the tested microbes and their combinations, the spores of Str. californicus
      proved to be the most potent inducer of cytotoxicity and inflammatory responses.
      These results indicate also that microbial coculture may support the growth of
      certain microbes with high immunotoxic potency such as Str.californicus.
      Furthermore, coculture containing S. chartarum and A. versicolor caused a
      synergistic increase in cytotoxicity compared to the sum response induced by the
      pure cultures, but no effect on inflammatory responses was detected. Generally,
      spore-induced cytotoxicity and production of inflammatory markers increased
      during the growth period from 5 to 10 wk, suggesting that the immunotoxic potency
      of spores increases with time.

PMID- 16087575
TI  - Does biomass exposure affect serum MDA levels in women?
AB  - It is believed that the inhalation of biomass fuel, a substance that is used for
      bread baking and heating in rural areas, is associated with chronic obstructive
      pulmonary disease (COPD) and pulmonary symptoms. The products of biomass are
      claimed to affect the oxidant/antioxidant imbalance, which plays a significant
      role in such a disease COPD. In our study, the serum level of malonyldialdehyde
      (MDA) was accepted as a marker of oxidant/antioxidant imbalance, and it was
      measured by the thiobarbituric acid method. A total of 43 women living in the
      central and rural areas of Diyarbakir was chosen randomly for the study and they
      were divided into two groups. The first group, also called the study population,
      consisted of 28 women living in rural areas. The mean age of the sample was 43 yr
      (range 31-63 yr). All were healthy and nonsmokers. Among these women the mean
      duration of the exposure to biomass was 12 h/wk for 25 yr. The mean MDA level (+/
      SD) was 3281 +/- 0.789 nmol/ml. The second group, the control population,
      consisted of 15 healthy women of age 42 yr (range 30-65 yr). They were again
      nonsmokers and healthy. These women were selected from the central Diyarbakir.
      The mean MDA level (+/-SD) was 1.474 +/- 0.630 nmol/ml. The difference between
      two populations were statistically significant (p < 0.0001). In conclusion, we
      believe that the high level of serum MDA in women is a result of biomass
      exposure.

PMID- 16087633
TI  - A new bioactive flavone glycoside from the seeds of Melilotus indica All.
AB  - Melilotus indica All. [Chopra, R.N., Nayar, S.L. and Chopra, I.C. (1956) Glossary
      Indian Med. Plants, 164 C.S.I.R. Publication New-Delhi; Kirtikar, K.R. and Basu,
      B.D. (1935) Indian Medicinal Plants, 2nd Ed., Vol. I, pp. 703-704 Lalit Mohan
      Basuan Co. Allahabad. The Wealth of India (1962) A Dictionary of Raw Materials
      and Industrial Products, Vol. VI, pp. 329-331 (C.S.I.R. Publication: New-Delhi)]
      belongs to family Leguminosae, which is commonly known as 'Banmethi' in Hindi. It
      is found in North India, extending into S. Persia, S. Europe and the Tropical
      zone of India. The seeds are used as an anthelmintic, an antipyretic, for curing
      heart diseases, bronchitis, leprosy, bowel complaints and infantile diarrhea. The
      plant has also been used as a discutient, emollient, and as a fomentation. It is
      also useful in a plaster for swelling. It is considered astringent and narcotic.
      Earlier workers have reported the presence of C-glycosides [Sayed, E.L., Ishak,
      M.S. and Mabry, T.J. (1997) Asian J. Chem., 9, 551], methylene-dioxypterocarpan
      (MIS6) [Saxena, V.K. and Nigam, S. (1997) Fitoterapia, 68, 343-345], pterocarpane
      (MIS2) [Saxena, V.K. and Nigam, S. (1996) J. Institution Chem. 68, 122-125] and
      prenylated pterocarpan [Saxena, V.K. and Nigam, S. (1997) Fitoterapia, 68, 403
      407] from this plant. Here, we report the isolation of the new flavone glycoside
      5,7,4'-trihydroxy-6,3'-dimethoxyflavone-7-O-alpha-L-arabinopyranosyl(1-->6)-O
      beta-D-galactopyranoside (1) from the seeds of this plant.

PMID- 16087634
TI  - Two new triterpene saponins from Lysimachia davurica.
AB  - Two new saponins, named davuricoside L (1) and davuricoside O (2), have been
      isolated from the whole plants of Lysimachia davurica. Their structures were
      determined by 1D and 2D NMR, FAB-MS techniques, and chemical methods.

PMID- 16087635
TI  - Therapeutic effects of hydroxysafflor yellow A on focal cerebral ischemic injury
      in rats and its primary mechanisms.
AB  - The therapeutic effects of hydroxysafflor yellow A (HSYA), extracted from
      Carthamus tinctorius. L, on focal cerebral ischemic injury in rats and its
      related mechanisms have been investigated. Focal cerebral ischemia in rats were
      made by inserting a monofilament suture into internal carotid artery to block the
      origin of the middle cerebral artery and administrated by HSYA via sublingular
      vein injection in doses of 1.5, 3.0, 6.0 mg kg(-1) at 30 min after the onset of
      ischemia, in comparison with the potency of nimodipine at a dose of 0.2 mg kg(
      1). Then, 24 h later, the evaluation for neurological deficit scores of the rats
      were recorded and postmortem infarct areas determined by quantitative image
      analysis. At the end of the experiment, blood samples were taken to determine
      plasma 6-Keto-PGF1alpha/TXB2 by radioimmunoassays and blood rheological
      parameters. The effects exerted by HSYA on thrombosis formation by artery vein by
      pass method and ADP-induced platelet aggregation in vivo and in vitro were
      investigated, respectively. The results indicated that more than 30% of the area
      of ischemic cerebrum was observed in the ischemic model group. HSYA dose
      dependently improved the neurological deficit scores and reduced the cerebral
      infarct area, and HSYA bore a similarity in potency of the therapeutic effects on
      focal cerebral ischemia to nimodipine. The inhibition rates of thrombosis
      formation by HSYA at the designated doses were 20.3%, 43.6% and 54.2%,
      respectively, compared with saline-treated group. Inhibitory activities of HSYA
      were observed on ADP-induced platelets aggregation in a dose-dependent manner,
      and the maximum inhibitory aggregation rate of HSYA was 41.8%. HSYA provided a
      suppressive effect on production of TXA2 without significant effect on plasma
      PGI2 concentrations. Blood rheological parameters were markedly improved by HSYA,
      such as whole blood viscosity (from 21.71 +/- 4.77 to 11.61 +/- 0.90 mPa.s),
      plasma viscosity (from 2.73 +/- 0.53 to 1.42 +/- 0.07 mPa.s), deformability (from
      0.66 +/- 0.26 to 0.77 +/- 0.33) and aggregation of erythrocyte (from 3.24 +/-
      0.41 to 2.57 +/- 0.30), but no significant effect of HSYA on homatocrit was found
      (from 51.38 +/- 4.68% to 49.91 +/- 2.32%). HSYA appears to be a good potential
      agent to treat focal cerebral ischemia, and the underlying mechanisms exerted by
      HSYA might be involved in its inhibitory effects on thrombosis formation and
      platelet aggregation as well as its beneficial action on regulation of PGI2/TXA2
      and blood rheological changes in rats.

PMID- 16087636
TI  - Flavonoids from Vitex trifolia L. inhibit cell cycle progression at G2/M phase
      and induce apoptosis in mammalian cancer cells.
AB  - Six flavonoids, persicogenin (1), artemetin (2), luteolin (3), penduletin (4),
      vitexicarpin (5) and chrysosplenol-D (6), have been isolated for the first time
      as new cell cycle inhibitors from Vitex trifolia L., a Chinese folk medicine used
      to treat cancers, through a bioassay-guided separation procedure. They were
      identified by spectroscopic methods. The inhibitory effects of 1-6 on the
      proliferation of mammalian cancer cells have been evaluated by the SRB
      (sulforhodamine B) method and their effects on cell cycle and apoptosis
      investigated by flow cytometry with the morphological observation under light
      microscope and by agarose-gel electrophoresis to detect internucleosomal DNA
      fragmentation. Compounds 1-6 inhibited the proliferation of mouse tsFT210 cancer
      cells with the IC50s (microg ml(-1)) > 100 (inhibition rate at 100 microg ml(-1),
      47.9%) for 1, >100 (inhibition rate at 100 microg ml(-1), 49.6 %) for 2, 10.7 for
      3, 19.8 for 4, 0.3 for 5, and 3.5 for 6. Flow cytometric investigations for 1-6
      demonstrated that 1-5 mainly inhibited cell cycle at the G2/M phase in a dose
      dependent manner with a weak induction of apoptosis on the tsFT210 cells, while 6
      induced mainly apoptosis of the same tsFT210 cells also in a dose-dependent
      manner together with a weak inhibition of the cell cycle at the G0/G1 and G2/M
      phases, demonstrating that 1-6 exert their anti-proliferative effect on tsFT210
      cells through inhibiting cell cycle and inducing apoptosis. In contrast to the
      cell cycle G2/M phase inhibitory main effect on tsFT210 cells, 5 induced mainly
      apoptosis on human myeloid leukemia K562 cells with a weak inhibition of the cell
      cycle at the G2/M phase. The present result provides flavonoids 1-6 as new cell
      cycle inhibitors and 1 and 4 as new anticancer flavonoids, which not only provide
      the first example of cell cycle G2/M phase inhibitory and apoptosis-inducing
      constituents of V. trifolia L. but also explain the use of Vitex trifolia L. by
      Chinese people to treat cancers.

PMID- 16087637
TI  - Two new constituents from Rheum sublanceolatum.
AB  - The chemical investigation of Rheum sublanceolatum has led to the isolation of
      two new constituents, the structures of which were identified on the basis of
      physical and spectroscopic analysis as 2-acetyl-3-methyl-6,8-dihydroxy-2,3,4,4
      tetrahydronaphthalene-1-one-6-O-beta-D-glucopyranoside (1) and 2,5-dimethyl-7
      hydroxychromone-7-O-beta-D-(6'-O-galloyl)-glucopyranoside (2).

PMID- 16087638
TI  - Resveratrol induces apoptosis and differentiation in acute promyelocytic leukemia
      (NB4) cells.
AB  - Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring
      phytoalexin found in grapes and wine, and has been reported to exert a variety of
      important pharmacological effects. We have investigated the activity of
      resveratrol on proliferation and differentiation of the acute promyelocytic
      leukemia cell line NB4. The growth inhibitory properties of resveratrol appear to
      be due to its induction of apoptotic cell death, as determined by morphological
      changes, DNA fragmentation, increased proportion of the subdiploid cell
      population and decreased mitochondrial transmembrane potential (Deltapsi(m)).
      Colorimetric assay for activity of caspase-3 showed an obvious increase in
      caspase-3 activity in cells after treatment with resveratrol. However, the
      expression levels of protein Bcl-2 and Bax show no significant change in response
      to resveratrol treatment. These results suggest that apoptosis of NB4 cells
      induced by resveratrol requires caspase-3 activation and is related to the
      mitochondrial transmembrane potential. The combination of resveratrol and all
      tran-retinoic acid (ATRA) induced 100% of the NB4 cells to become NBT-positive,
      whereas only a small part of cells became positive for NBT after a similar
      exposure to either resveratrol or ATRA alone. Thus, resveratrol may be useful in
      treating acute promyelocytic leukemia.

PMID- 16087639
TI  - A new minor triterpene saponin from kaixin-san prescription.
AB  - A new minor oleanane-type saponin, ginsenoside-R(OA) (1), has been isolated from
      the extract of Kaixin-San, a prescription composed of Panax ginseng and other
      medicinal herbs, together with 15 known ginsenosides. The structure of 1 was
      established as 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosyl
      oleanolic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside by
      chemical and spectroscopic evidence. In addition, the presence of ginsenoside
      R(OA) in ginseng was confirmed by HPLC-ESI-MS.

PMID- 16087640
TI  - A new sterol glycoside from Securidaca inappendiculata.
AB  - From the roots of Securidaca inappendiculata, one new sterol glycoside
      securisteroside (1) has been isolated, along with two known sterols, spinasterol
      (2) and 3-O-beta-D-glucopyranosyl-spinasterol (3). The new sterol was
      characterized by chemical and spectrometric methods, including EIMS, FABMS and
      one- and two-dimensional NMR experiments.

PMID- 16087641
TI  - Total synthesis of scutellarin-7-O-glucuronide.
AB  - Scutellarin-7-O-glucuronide (1) has been synthesized from 2-hydroxyl-4,5,6
      trimethoxyacetophenone through eight steps, including Michael addition,
      cyclization, hydrogenation, hydroxyl protection, deprotection, etc. The overall
      yield of 13% is much higher than that reported (0.6%) by L. Farkas, G. Mezey
      Vandor et al. in 1974.

PMID- 16087642
TI  - Seven new meroditerpenoids, from the marine sponge Strongylophora strongylata,
      that inhibited the maturation of starfish oocytes.
AB  - Seven new meroditerpenoids, strongylophorines 13-19 (1-7), have been isolated
      together with the four known strongylophorines 2 (8), 3 (9), 4 (10), and 8 (11)
      by a screening method using oocytes of the starfish Asterina pectinifera from a
      marine sponge Strongylophora strongylata collected at Iriomote Island, Okinawa,
      Japan. The structures were assigned according to their spectral data. Ten
      strongylophorines inhibited the maturation of starfish oocytes in the range 1.1
      37.6 microM (IC50), while strongylophorine 4 (10) was not active at 250 microM.

PMID- 16087643
TI  - A new biologically active flavonol glycoside from Psoralea corylifolia (Linn.).
AB  - A new biologically active flavonol glycoside (1) mp 264-265 degrees C, C32H38O20,
      [M]+ 742 (EIMS) has been isolated from the methanol-soluble fraction of the
      defatted seeds of Psoralea corylifolia (Linn.). It was characterised as the new
      flavonol glycoside 3,5,3',4'-tetrahydroxy-7-methoxyflavone-3'-O-alpha-L
      xylopyranosyl(1-->3)-O-alpha-L-arabinopyranosyl(1-->4)-O-beta-D-galactopyranoside
      by several colour reactions, spectral analysis and chemical degradations.
      Compound 1 showed anti-microbial activity against various bacteria and fungi.

PMID- 16087644
TI  - Two new compounds from Glycyrrhiza glabra.
AB  - Two new flavonosides have been isolated from the roots of Glychirriza glabra and
      identified as 5,8-dihydroxy-flavone-7-O-beta-D-glucuronide, glychionide A, and 5
      hydroxy-8-methoxyl-flavone-7-O-beta-D-glucuronide, glychionide B.

PMID- 16087645
TI  - A new compound from Rhododendren anthopogonosides maxim.
AB  - A new compound, (2R)-4-phenyl-2-O-[beta-D-xylopyranosyl(1-->6)-beta-D
      glucopyranosyl]butane (1), has been isolated from the aerial parts of
      Rhododendren anthopogonoides, together with two known compounds, fraxin (2), and
      lyoniside (3). Their structures were determined by means of physico-chemical
      evidence and spectral analyses, including UV, IR, HR-FABMS, 1H and 13C NMR, and
      2D NMR data.

PMID- 16087646
TI  - Lipid lowering and recurrent stroke: another stroke paradox?

PMID- 16087647
TI  - The role of non-invasive imaging in the risk stratification of asymptomatic
      diabetic subjects.
AB  - AIMS: Coronary artery disease (CAD) is the leading cause of death in patients
      with diabetes. Patients often present with advanced and asymptomatic disease.
      Proposed strategies that may favourably affect CAD risk and outcomes in this
      patient population include identifying diabetic patients with subclinical disease
      at high risk of future cardiac events. The purpose of this article was to review
      the role of both atherosclerosis imaging tests (coronary calcium imaging and high
      resolution ultrasound assessment of carotid intima-media thickness) and
      functional imaging techniques [stress echocardiography and radionuclide
      myocardial perfusion imaging (MPI)] in the diagnostic and prognostic evaluation
      of asymptomatic diabetic subjects. METHODS AND RESULTS: We identified studies
      using MEDLINE searches (1966 to April 2005) and by reviewing reference lists. A
      comprehensive list of search terms was applied. All stress echocardiography and
      MPI studies evaluating the prevalence and/or prognostic value of myocardial
      ischaemia (n = 19) and coronary calcium imaging studies (n = 2) evaluating the
      prognostic value of subclinical atherosclerosis in diabetic patients were
      included. CONCLUSION: Asymptomatic myocardial ischaemia can be detected in a
      significant proportion of diabetic subjects by non-invasive imaging tests such as
      MPI and stress echocardiography. The results of ongoing and future studies may be
      helpful in guiding the selection of asymptomatic diabetic subjects to undergo non
      invasive imaging, establishing the cost-effectiveness of various testing
      strategies and their impact on prognosis.

PMID- 16087648
TI  - Gene-specific modifying effects of pro-LVH polymorphisms involving the renin
      angiotensin-aldosterone system among 389 unrelated patients with hypertrophic
      cardiomyopathy.
AB  - AIMS: The purpose of this study was to determine whether the deletion/insertion
      (D/I) polymorphism in the ACE-encoded angiotensin-converting enzyme or the pooled
      gene effect of five renin-angiotensin-aldosterone system (RAAS) polymorphisms
      were disease modifiers in a large cohort of unrelated patients with genotyped
      hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Five different RAAS
      polymorphism genotypes were established by PCR amplification of the surrounding
      polymorphic regions of genomic DNA in a cohort of 389 unrelated patients
      comprehensively genotyped for HCM-causing mutations in eight
      sarcomeric/myofilament genes. Patient clinical data were archived in a database
      blinded both to the primary myofilament defect and the polymorphism genotype.
      Each patient was assessed with respect to ACE genotype as well as composite pro
      left ventricular hypertrophy (LVH) RAAS polymorphism score (0-5). Overall, no
      clinical parameter correlated independently with ACE genotype. Subset analysis of
      the two most common genetic subtypes of HCM, MYBPC3 (myosin binding protein C)
      and MYH7 (beta myosin heavy chain), demonstrated a significant pro-LVH effect of
      DD-ACE only in patients with MYBPC3-HCM. In MYBPC3-HCM, left ventricular wall
      thickness was greater in patients with DD genotype (25.8+/-5 mm) compared with DI
      (21.8+/-4) or II genotype (20.8+/-5, P=0.01). Moreover, extreme hypertrophy (>30
      mm) was only seen in MYBPC3-HCM patients who also hosted DD-ACE. An effect of
      RAAS pro-LVH score was evident only in the subgroup of patients with no
      previously identified myofilament mutation. CONCLUSION: This study demonstrates
      that RAAS genotypes may modify the clinical phenotype of HCM in a disease gene
      specific fashion rather than indiscriminately.

PMID- 16087649
TI  - Diagnostic discrimination between graft-related and non-graft-related
      perioperative myocardial infarction with cardiac troponin I after coronary artery
      bypass surgery.
AB  - AIMS: The rise of markers for myocardial injury indicates early graft-related or
      non-graft-related perioperative myocardial infarction (PMI) after coronary artery
      bypass grafting (CABG). A diagnostic discrimination between these two situations
      may enable adequate therapeutic measures, limiting myocardial damage, and
      improving outcome. METHODS AND RESULTS: In a prospective study, 94 among 3308
      consecutive CABG patients underwent acute reangiography because of evidence of
      PMI. Of these 94 patients, 56 had graft-related PMI (group 1), 38 patients had
      non-graft-related PMI (group 2), and 95 patients without evidence of PMI and
      angiographically patent grafts served as control (group 3). Cardiac troponin I
      (cTnI), creatine kinase (CK), and its MB fraction were determined. CTnI, but not
      CK/CK-MB levels were significantly higher in group 1 than in groups 2 and 3 at 12
      and 24 h after aortic unclamping (P<0.0001). Receiver operating characteristic
      and multivariable logistic regression analyses indicated cTnI as the best
      discriminator between PMI 'in general' and 'inherent' release of cTnI after CABG
      with a cut-off value of 10.5 ng/mL and between graft-related and non-graft
      related PMI with a cut-off value of 35.5 ng/mL. CONCLUSION: Perioperative cTnI
      elevation after CABG separates among patients with graft-related, non-graft
      related, and without PMI, however, not earlier than 12 h after surgery.

PMID- 16087650
TI  - Impact of the elevation of biochemical markers of myocardial damage on long-term
      mortality after percutaneous coronary intervention: results of the CK-MB and PCI
      study.

PMID- 16087651
TI  - Antibody mimics based on human fibronectin type three domain engineered for
      thermostability and high-affinity binding to vascular endothelial growth factor
      receptor two.
AB  - The tenth human fibronectin type three domain ((10)Fn3) is a small (10 kDa),
      extremely stable and soluble protein with an immunoglobulin-like fold, but
      without cysteine residues. Selections from (10)Fn3-based libraries of proteins
      with randomized loops have yielded high-affinity, target-specific antibody
      mimics. However, little is known about the biophysical properties of such
      antibody mimics, which will determine their suitability for in vitro and medical
      applications. We characterized target binding and biophysical properties of two
      related (10)Fn3-based antibody mimics that bind vascular endothelial growth
      factor receptor two (VEGF-R2). The first antibody mimic, which has a dissociation
      constant (K(d)) of 13 nM, is highly stable [melting temperature (T(m))=62 degrees
      C] and soluble, whereas the second, which binds VEGF-R2 with 40 x higher
      affinity, is less stable (T(m) < 40 degrees C) and relatively insoluble. We used
      our understanding of these two (10)Fn3 derivatives and of wild-type (10)Fn3
      structure to engineer the next generation of antibody mimics, which have an
      improved combination of high affinity (K(d)=0.59 nM), stability (T(m)=53 degrees
      C) and solubility. Our findings illustrate that (10)Fn3-based antibody mimics can
      be engineered for favorable biophysical properties even when 20% of the wild-type
      (10)Fn3 sequence is mutated in order to satisfy target-binding requirements.

PMID- 16087652
TI  - A distinct strategy to generate high-affinity peptide binders to receptor
      tyrosine kinases.
AB  - We describe a novel and general way of generating high affinity peptide (HAP)
      binders to receptor tyrosine kinases (RTKs), using a multi-step process
      comprising phage-display selection, identification of peptide pairs suitable for
      hetero-dimerization (non-competitive and synergistic) and chemical synthesis of
      heterodimers. Using this strategy, we generated HAPs with K(D)s below 1 nM for
      VEGF receptor-2 (VEGFR-2) and c-Met. VEGFR-2 HAPs bound significantly better (6-
      to 500-fold) than either of the individual peptides that were used for
      heterodimer synthesis. Most significantly, HAPs were much better (150- to 800
      fold) competitors than monomers of the natural ligand (VEGF) in various
      competitive binding and functional assays. In addition, we also found the binding
      of HAPs to be less sensitive to serum than their component peptides. We believe
      that this method may be applied to any protein for generating high affinity
      peptide (HAP) binders.

PMID- 16087653
TI  - Quantitative measurement of protein stability from unfolding equilibria monitored
      with the fluorescence maximum wavelength.
AB  - The fluorescence of tryptophan is used as a signal to monitor the unfolding of
      proteins, in particular the intensity of fluorescence and the wavelength of its
      maximum lambda(max). The law of the signal is linear with respect to the
      concentrations of the reactants for the intensity but not for lambda(max).
      Consequently, the stability of a protein and its variation upon mutation cannot
      be deduced directly from measurements made with lambda(max). Here, we established
      a rigorous law of the signal for lambda(max). We then compared the stability
      DeltaG(H(2)O) and coefficient of cooperativity m for a two-state equilibrium of
      unfolding, monitored with lambda(max), when the rigorous and empirical linear
      laws of the signal are applied. The corrective terms involve the curvature of the
      emission spectra at their lambda(max) and can be determined experimentally. The
      rigorous and empirical values of the cooperativity coefficient m are equal within
      the experimental error for this parameter. In contrast, the rigorous and
      empirical values of the stability DeltaG(H(2)O) generally differ. However, they
      are equal within the experimental error if the curvatures of the spectra for the
      native and unfolded states are identical. We validated this analysis
      experimentally using domain 3 of the envelope glycoprotein of the dengue virus
      and the single-chain variable fragment (scFv) of antibody mAbD1.3, directed
      against lysozyme.

PMID- 16087654
TI  - Does dietary folate intake modify effect of alcohol consumption on breast cancer
      risk? Prospective cohort study.
AB  - OBJECTIVE: To evaluate the effect of dietary folate intake on the relation
      between alcohol consumption and breast cancer risk. DESIGN: Prospective cohort
      study. SETTING: Melbourne, Australia. PARTICIPANTS: 17,447 Anglo-Australian women
      resident in Melbourne, aged 40-69 years at recruitment in 1990-4, and followed up
      until 31 December 2003. MAIN OUTCOME MEASURE: Invasive breast cancers diagnosed
      during follow-up and ascertained through the Victorian cancer registry. RESULTS:
      537 invasive breast cancers were diagnosed. Compared with lifetime abstainers,
      the hazard ratio for breast cancer in women who consumed an average of 40 g or
      more of alcohol daily at baseline was 1.41 (95% confidence interval 0.90 to
      2.23). No direct association was found between dietary folate intake and risk of
      breast cancer, but a high folate intake mitigated the excess risk associated with
      alcohol. The estimated hazard ratio of an alcohol consumption of 40 g/day or more
      was 2.00 (1.14 to 3.49) for women with intakes of 200 mug/day of folate and 0.77
      (0.33 to 1.80) for 400 mug/day of folate (P = 0.04 for interaction between
      alcohol and folate). CONCLUSIONS: An adequate dietary intake of folate might
      protect against the increased risk of breast cancer associated with alcohol
      consumption.

PMID- 16087655
TI  - Bacterial prostatitis due to Pseudomonas aeruginosa harbouring the blaVIM-2
      metallo-{beta}-lactamase gene from Saudi Arabia.

PMID- 16087656
TI  - Disc methods for detecting AmpC {beta}-lactamase-producing clinical isolates of
      Escherichia coli and Klebsiella pneumoniae.

PMID- 16087657
TI  - Self-reported alcohol use among Dutch emergency room patients: variations in
      prevalence rates owing to methodological differences.
AB  - AIMS: This study compared different methods of assessing self-reported alcohol
      use among emergency room patients in order to explain the variations in reported
      prevalence rates. METHODS: Alcohol use prior to patient's injury or illness was
      assessed in one hospital by a self-report questionnaire in three different ways:
      (i) administered by emergency room staff, (ii) administered by research staff, or
      (iii) sent to the patient's home by post. RESULTS: Results show variations in
      self-reported alcohol use 6 h prior to the injury or illness ranging from 4.6 to
      9.1%; these variations may be explained by sample selection bias and
      characteristics of the included study populations. When self-report is combined
      with staff judgement the corresponding prevalence rates are 6.8% for research
      staff and 16.2% for emergency room staff. This shows that the latter judge the
      patient's alcohol use more efficiently than the research staff. Using research
      staff 24 h a day resulted in almost no sample bias. Data collection via emergency
      room staff leads to the highest alcohol use prevalence rates and to the highest
      sample bias; this was influenced by the emergency room characteristics. A
      retrospective mail survey results in an older sample with age-related (lower)
      alcohol use and emergency room characteristics related to this age group.
      CONCLUSIONS: Future studies using patient self-report among emergency room
      samples should consider carefully the influence of sample selection bias. The
      combination of the research staff handing out the questionnaire and the emergency
      room staff giving their judgement on the patient's alcohol use seems to be a
      useful method.

PMID- 16087658
TI  - Current alcohol use is associated with a reduced risk of hot flashes in midlife
      women.
AB  - AIMS: To examine the relation between current alcohol use, estradiol, estrone,
      and testosterone levels, and hot flashes in midlife women using a case-control
      study design. METHODS: Cases were midlife women (45-54 years) who reported ever
      experiencing hot flashes. Controls were midlife women (45-54 years) who reported
      never experiencing hot flashes. Each participant completed a questionnaire and
      provided a blood sample that was used to measure estradiol, estrone, and
      testosterone levels by enzyme-linked immunosorbent assay. RESULTS: The results
      indicate that current alcohol use (at least one day per month) was significantly
      associated with a reduced risk of hot flashes compared to non-use of alcohol,
      independent of age and smoking habits. The hot flashes experienced by current
      alcohol users were less severe and less frequent than those experienced by non
      users of alcohol. Further, current alcohol users had similar levels of estradiol,
      estrone, and testosterone compared to non-users of alcohol. CONCLUSIONS: These
      data suggest that current alcohol use is associated with a reduced risk of any,
      severe, and frequent hot flashes in midlife women by a mechanism that may not
      include changes in sex steroid hormone levels.

PMID- 16087659
TI  - Social capital, the miniaturization of community and high alcohol consumption: a
      population-based study.
AB  - AIMS: To study the impact of social participation, trust, and the miniaturization
      of community, i.e. high social participation/low trust, on the risk of high
      alcohol consumption. METHODS: The Scania 2000 public health survey is a cross
      sectional, postal questionnaire study. A total of 13 604 persons aged 18-80 years
      were included. A logistic regression model was used to investigate the
      association between the social capital variables and high alcohol consumption
      (168.0 g/week or more for men and 108.0 g/week or more for women). The
      multivariate analyses analysed the importance of confounders (age, country of
      origin, education, and economic stress) on the risk of high alcohol consumption
      according to the social capital variables. RESULTS: A 14.0% proportion of all men
      and 7.8% of all women had an alcohol consumption above recommended levels. High
      alcohol consumption above recommended levels was not associated with social
      participation but negatively associated with trust among men. The miniaturization
      of community category, i.e. high social participation/low trust, had
      significantly higher risks of high alcohol consumption compared to the high
      social capital (high social participation/high trust) category among men.
      CONCLUSION: High social participation combined with low trust, i.e. the
      miniaturization of community, is positively associated high alcohol consumption
      among men. A structural/social factor which may affect the amount of alcohol
      consumed has thus been identified in this study.

PMID- 16087660
TI  - Enhanced rate of ethanol elimination from blood after intravenous administration
      of amino acids compared with equicaloric glucose.
AB  - AIMS: To investigate the effect of an amino acid mixture given intravenously
      (i.v.) on the rate of ethanol elimination from blood compared with equicaloric
      glucose and Ringer's acetate as control treatments. METHODS: In a randomized
      cross-over study, six healthy men (mean age 23 years) fasted overnight before
      receiving either Ringer's acetate, glucose or the amino acid mixture (Vamin 18 g
      N/l) by constant rate i.v. infusion over 4.5 h. Ethanol (0.4 g/kg) was given by
      an i.v. infusion lasting 60 min during the time each of the treatments was
      administered. At various times post-infusion, blood samples were taken for
      determination of ethanol by headspace gas chromatography. Blood glucose and heart
      rate were monitored at regular intervals. Concentration-time profiles of ethanol
      were plotted for each subject and the rate of ethanol disappearance from blood as
      well as other pharmacokinetic parameters were compared by repeated measures
      analysis of variance. RESULTS: The rate of ethanol elimination from blood was
      increased significantly (P < 0.001) after treatment with amino acids (mean +/-
      SD, 0.174 +/- 0.011 g/l/h) compared with equicaloric glucose (0.121 +/- 0.016
      g/l/h) or Ringer's acetate (0.110 +/- 0.013 g/l/h). Heart rate was also slightly
      higher during infusion of the amino acid mixture (P < 0.05). CONCLUSIONS: When
      the rate of ethanol elimination from blood is relatively slow, such as after an
      overnight fast, it can be increased by approximately 60% after treatment with
      i.v. amino acids. The efficacy of amino acid treatment was not related to the
      supply of calories because glucose was no more effective than Ringer's acetate.
      We suggest that amino acids might increase hepatic oxygen consumption, resulting
      in a more effective conversion of NADH to NAD+ in mitochondria. An important
      feature of the experimental design was ensuring hepatic availability of amino
      acids during much of the time that ethanol was being metabolized.

PMID- 16087662
TI  - The Epstein-Barr virus protein, latent membrane protein 2A, co-opts tyrosine
      kinases used by the T cell receptor.
AB  - Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis and
      is associated with several human malignancies. The EBV protein latent membrane
      protein 2A (LMP2A) promotes viral latency in memory B cells by interfering with B
      cell receptor signaling and provides a survival signal for mature B cells that
      have lost expression of surface immunoglobulin. The latter function has suggested
      that LMP2A may enhance the survival of EBV-positive tumors. EBV is associated
      with several T cell malignancies and, since LMP2A has been detected in several of
      these disorders, we examined the ability of LMP2A to transmit signals and
      interfere with T cell receptor signaling in T cells. We show that LMP2A is
      tyrosine-phosphorylated in Jurkat TAg T cells, which requires expression of the
      Src family tyrosine kinases, Lck and Fyn. Lck and Fyn are recruited to the
      tyrosine-phosphorylated Tyr112 site in LMP2A, whereas phosphorylation of an ITAM
      motif in LMP2A creates a binding site for the ZAP-70/Syk tyrosine kinases. LMP2A
      also associates through its two PPPPY motifs with AIP4, a NEDD4 family E3
      ubiquitin ligase; this interaction results in ubiquitylation of LMP2A and serves
      to regulate the stability of LMP2A and LMP2A-kinase complexes. Furthermore,
      stable expression of LMP2A in Jurkat T cells down-regulated T cell receptor
      levels and attenuated T cell receptor signaling. Thus, through recruiting
      tyrosine kinases involved in T cell receptor activation, LMP2A may provide a
      survival signal for EBV-positive T cell tumors, whereas LMP2A-associated NEDD4 E3
      ligases probably titer the strength of this signal.

PMID- 16087661
TI  - Anthrax biosensor, protective antigen ion channel asymmetric blockade.
AB  - The significant threat posed by biological agents (e.g. anthrax, tetanus,
      botulinum, and diphtheria toxins) (Inglesby, T. V., O'Toole, T., Henderson, D.
      A., Bartlett, J. G., Ascher, M. S., Eitzen, E., Friedlander, A. M., Gerberding,
      J., Hauer, J., Hughes, J., McDade, J., Osterholm, M. T., Parker, G., Perl, T. M.,
      Russell, P. K., and Tonat, K. (2002) J. Am. Med. Assoc. 287, 2236-2252) requires
      innovative technologies and approaches to understand the mechanisms of toxin
      action and to develop better therapies. Anthrax toxins are formed from three
      proteins secreted by fully virulent Bacillus anthracis, protective antigen (PA,
      83 kDa), lethal factor (LF, 90 kDa), and edema factor (EF, 89 kDa). Here we
      present electrophysiological measurements demonstrating that full-length LF and
      EF convert the current-voltage relationship of the heptameric PA63 ion channel
      from slightly nonlinear to highly rectifying and diode-like at pH 6.6. This
      effect provides a novel method for characterizing functional toxin interactions.
      The method confirms that a previously well characterized PA63 monoclonal
      antibody, which neutralizes anthrax lethal toxin in animals in vivo and in vitro,
      prevents the binding of LF to the PA63 pore. The technique can also detect the
      presence of anthrax lethal toxin complex from plasma of infected animals. The
      latter two results suggest the potential application of PA63 nanopore-based
      biosensors in anthrax therapeutics and diagnostics.

PMID- 16087663
TI  - The respiratory substrate rhodoquinol induces Q-cycle bypass reactions in the
      yeast cytochrome bc(1) complex: mechanistic and physiological implications.
AB  - The mitochondrial cytochrome bc(1) complex catalyzes the transfer of electrons
      from ubiquinol to cyt c while generating a proton motive force for ATP synthesis
      via the "Q-cycle" mechanism. Under certain conditions electron flow through the Q
      cycle is blocked at the level of a reactive intermediate in the quinol oxidase
      site of the enzyme, resulting in "bypass reactions," some of which lead to
      superoxide production. Using analogs of the respiratory substrates ubiquinol-3
      and rhodoquinol-3, we show that the relative rates of Q-cycle bypass reactions in
      the Saccharomyces cerevisiae cyt bc(1) complex are highly dependent by a factor
      of up to 100-fold on the properties of the substrate quinol. Our results suggest
      that the rate of Q-cycle bypass reactions is dependent on the steady state
      concentration of reactive intermediates produced at the quinol oxidase site of
      the enzyme. We conclude that normal operation of the Q-cycle requires a fairly
      narrow window of redox potentials with respect to the quinol substrate to allow
      normal turnover of the complex while preventing potentially damaging bypass
      reactions.

PMID- 16087664
TI  - Cys-tRNA(Pro) editing by Haemophilus influenzae YbaK via a novel
      synthetase.YbaK.tRNA ternary complex.
AB  - Aminoacyl-tRNA synthetases are multidomain enzymes that often possess two
      activities to ensure translational accuracy. A synthetic active site catalyzes
      tRNA aminoacylation, while an editing active site hydrolyzes mischarged tRNAs.
      Prolyl-tRNA synthetases (ProRS) have been shown to misacylate Cys onto tRNA(Pro),
      but lack a Cys-specific editing function. The synthetase-like Haemophilus
      influenzae YbaK protein was recently shown to hydrolyze misacylated Cys-tRNA(Pro)
      in trans. However, the mechanism of specific substrate selection by this single
      domain hydrolase is unknown. Here, we demonstrate that YbaK alone appears to lack
      specific tRNA recognition capabilities. Moreover, YbaK cannot compete for
      aminoacyl-tRNAs in the presence of elongation factor Tu, suggesting that YbaK
      acts before release of the aminoacyl-tRNA from the synthetase. In support of this
      idea, cross-linking studies reveal the formation of binary (ProRS.YbaK) and
      ternary (ProRS.YbaK.tRNA) complexes. The binding constants for the interaction
      between ProRS and YbaK are 550 nM and 45 nM in the absence and presence of
      tRNA(Pro), respectively. These results suggest that the specificity of trans
      editing by YbaK is ensured through formation of a novel ProRS.YbaK.tRNA complex.

PMID- 16087665
TI  - Mso1 is a novel component of the yeast exocytic SNARE complex.
AB  - The yeast exocytic SNARE complex consists of one molecule each of the Sso1/2
      target SNAREs, Snc1/2 vesicular SNAREs, and the Sec9 target SNARE, which form a
      fusion complex that is conserved in evolution. Another protein, Sec1, binds to
      the SNARE complex to facilitate assembly. We show that Mso1, a Sec1-interacting
      protein, also binds to the SNARE complex and plays a role in mediating Sec1
      functions. Like Sec1, Mso1 bound to SNAREs in cells containing SNARE complexes
      (i.e. wild-type, sec1-1, and sec18-1 cells), but not in cells in which complex
      formation is inhibited (i.e. sec4-8 cells). Nevertheless, Mso1 remained
      associated with Sec1 even in sec4-8 cells, indicating that they act as a pair.
      Mso1 localized primarily to the plasma membrane of the bud when SNARE complex
      formation was not impaired but was mostly in the cytoplasm when assembly was
      prevented. Genetic studies suggest that Mso1 enhances Sec1 function while
      attenuating Sec4 GTPase function. This dual action may impart temporal regulation
      between Sec4 turnoff and Sec1-mediated SNARE assembly. Notably, a small region at
      the C terminus of Mso1 is conserved in the mammalian Munc13/Mint proteins and is
      necessary for proper membrane localization. Overexpression of Mso1 lacking this
      domain (Mso1-(1-193)) inhibited the growth of cells bearing an attenuated Sec4
      GTPase. These results suggest that Mso1 is a component of the exocytic SNARE
      complex and a possible ortholog of the Munc13/Mint proteins.

PMID- 16087666
TI  - Regulation of the dynamics of hsp90 action on the glucocorticoid receptor by
      acetylation/deacetylation of the chaperone.
AB  - It is known that inhibition of histone deacetylases (HDACs) leads to acetylation
      of the abundant protein chaperone hsp90. In a recent study, we have shown that
      knockdown of HDAC6 by a specific small interfering RNA leads to hyperacetylation
      of hsp90 and that the glucocorticoid receptor (GR), an established hsp90 "client"
      protein, is defective in ligand binding, nuclear translocation, and gene
      activation in HDAC6-deficient cells (Kovacs, J. J., Murphy, P. J. M., Gaillard,
      S., Zhao, X., Wu, J-T., Nicchitta, C. V., Yoshida, M., Toft, D. O., Pratt, W. B.,
      and Yao, T-P. (2005) Mol. Cell 18, 601-607). Using human embryonic kidney wild
      type and HDAC6 (small interfering RNA) knockdown cells transiently expressing the
      mouse GR, we show here that the intrinsic properties of the receptor protein
      itself are not affected by HDAC6 knockdown, but the knockdown cytosol has a
      markedly decreased ability to assemble stable GR.hsp90 heterocomplexes and
      generate stable steroid binding activity under cell-free conditions. HDAC6
      knockdown cytosol has the same ability to carry out dynamic GR.hsp90
      heterocomplex assembly as wild-type cytosol. Addition of purified hsp90 to HDAC6
      knockdown cytosol restores stable GR.hsp90 heterocomplex assembly to the level of
      wild-type cytosol. hsp90 from HDAC6 knockdown cytosol has decreased ATP-binding
      affinity, and it does not assemble stable GR.hsp90 heterocomplexes when it is a
      component of a purified five-protein assembly system. Incubation of knockdown
      cell hsp90 with purified HDAC6 converts the hsp90 to wild-type behavior. Thus,
      acetylation of hsp90 results in dynamic GR.hsp90 heterocomplex
      assembly/disassembly, and this is manifest in the cell as a approximately 100
      fold shift to the right in the steroid dose response for gene activation.

PMID- 16087667
TI  - CD46 plays a key role in tailoring innate immune recognition of apoptotic and
      necrotic cells.
AB  - Complement is the canonical innate immune system involved in host defense and
      tissue repair with the clearance of cell debris. In contrast to the robust armory
      mounted against microbial nonself-pathogens, complement is selectively activated
      on altered self (i.e. apoptotic and necrotic cells) to instruct the safe demise
      by poorly characterized mechanisms. Our data shed new light on the role of
      complement C1q in sensing nucleic acids (NA) rapidly exposed on apoptotic Jurkat
      T cell membranes and in driving C3 opsonization but without the lytic membrane
      attack complex. DNA/RNase-treated apoptotic cells failed to activate complement.
      We found that several other apoptotic cell models, including senescent
      keratinocytes, ionophore-treated sperm cells, and CMK-derived platelets, stained
      for cleaved caspase 3 were rapidly losing the key complement regulator CD46. CD46
      from nuclear and membrane stores was found to cluster into blebs and shed into
      microparticles together with NA, phosphatidylserine, C1q, and factor H. Classical
      and alternative pathways of complement were involved in the recognition of H2O2
      treated necrotic cells. Membrane attack complex was detected on necrotic cells
      possibly as a result of CD46 and CD59 shedding into soluble forms. Our data
      highlight a novel and universal paradigm whereby the complement innate immune
      system is using two synergistic strategies with the recognition of altered self
      NA and missing self-CD46 signals to instruct and tailor the efficient removal of
      apoptotic and necrotic cells in immunoprivileged sites.

PMID- 16087668
TI  - In vitro studies of cross-resistance mutations against two hepatitis C virus
      serine protease inhibitors, VX-950 and BILN 2061.
AB  - VX-950 is a potent, small molecule, peptidomimetic inhibitor of the hepatitis C
      virus (HCV) NS3.4A serine protease and has recently been shown to possess
      antiviral activity in a phase I trial in patients chronically infected with
      genotype 1 HCV. In a previous study, we described in vitro resistance mutations
      against either VX-950 or another HCV NS3.4A protease inhibitor, BILN 2061. Single
      amino acid substitutions that conferred drug resistance (distinct for either
      inhibitor) were identified in the HCV NS3 serine protease domain. The dominant VX
      950-resistant mutant (A156S) remains sensitive to BILN 2061. The major BILN 2061
      resistant mutants (D168V and D168A) are fully susceptible to VX-950. Modeling
      analysis suggested that there are different mechanisms of resistance for these
      mutations induced by VX-950 or BILN 2061. In this study, we identified mutants
      that are cross-resistant to both HCV protease inhibitors. The cross-resistance
      conferred by substitution of Ala(156) with either Val or Thr was confirmed by
      characterization of the purified enzymes and reconstituted replicon cells
      containing the single amino acid substitution A156V or A156T. Both cross
      resistance mutations (A156V and A156T) displayed significantly diminished fitness
      (or replication capacity) in a transient replicon cell system.

PMID- 16087669
TI  - A conserved glutamate residue in transmembrane helix 10 influences substrate
      specificity of rabbit OCT2 (SLC22A2).
AB  - OCT1 and OCT2 are involved in renal secretion of cationic drugs. Although they
      have similar selectivity for some substrates (e.g. tetraethylammonium (TEA)),
      they have distinct selectivities for others (e.g. cimetidine). We postulated that
      "homolog-specific residues," i.e. the 24 residues that are conserved in OCT1
      orthologs as one amino acid and in OCT2 as a different one, influence homolog
      specific selectivity and examined the influence on substrate binding of three of
      these conserved residues that are found in the C-terminal half of the rabbit
      orthologs of OCT1/2. The N353L and R403I substitutions (OCT2 to OCT1) did not
      significantly change the properties of OCT2. However, the E447Q replacement
      shifted substrate selectivity toward an OCT1-like phenotype. Substitution of
      glutamate with cationic amino acids (E447K and E447R) abolished transport
      activity, and the E447L mutant displayed markedly reduced transport of TEA and
      cimetidine while retaining transport of 1-methyl-4-phenylpyridinium. In a novel
      homology model of the three-dimensional structure of OCT2, Glu(447) was found in
      a putative docking region within a hydrophilic cleft of the protein. In addition,
      six residues identified in separate studies as exerting significant effects on
      OCT binding were also found within the putative cleft region. There was a
      significant correlation (r(2) = 0.82) between the IC(50) values for inhibition of
      TEA transport by 14 different compounds and their calculated K(D) values for
      binding to the model of rabbit OCT2. The results suggest that homology modeling
      offers an opportunity to direct future site-directed studies of OCT/substrate
      interaction.

PMID- 16087670
TI  - Pex3p initiates the formation of a preperoxisomal compartment from a subdomain of
      the endoplasmic reticulum in Saccharomyces cerevisiae.
AB  - Peroxisomes are dynamic organelles that often proliferate in response to
      compounds that they metabolize. Peroxisomes can proliferate by two apparent
      mechanisms, division of preexisting peroxisomes and de novo synthesis of
      peroxisomes. Evidence for de novo peroxisome synthesis comes from studies of
      cells lacking the peroxisomal integral membrane peroxin Pex3p. These cells lack
      peroxisomes, but peroxisomes can assemble upon reintroduction of Pex3p. The
      source of these peroxisomes has been the subject of debate. Here, we show that
      the amino-terminal 46 amino acids of Pex3p of Saccharomyces cerevisiae target to
      a subdomain of the endoplasmic reticulum and initiate the formation of a
      preperoxisomal compartment for de novo peroxisome synthesis. In vivo video
      microscopy showed that this preperoxisomal compartment can import both
      peroxisomal matrix and membrane proteins leading to the formation of bona fide
      peroxisomes through the continued activity of full-length Pex3p. Peroxisome
      formation from the preperoxisomal compartment depends on the activity of the
      genes PEX14 and PEX19, which are required for the targeting of peroxisomal matrix
      and membrane proteins, respectively. Our findings support a direct role for the
      endoplasmic reticulum in de novo peroxisome formation.

PMID- 16087671
TI  - Smad-dependent cooperative regulation of interleukin 2 receptor alpha chain gene
      expression by T cell receptor and transforming growth factor-beta.
AB  - The interleukin 2 receptor alpha chain (IL-2Ralpha) is a component of high
      affinity IL-2 receptors and thus critically regulates T cell growth and other
      lymphoid functions. Five positive regulatory regions together control lineage
      restricted and activation-dependent IL-2Ralpha induction in response to antigen
      and IL-2. We now show that TGF-beta cooperates with T cell receptor (TCR)
      signaling to increase IL-2Ralpha gene expression. Moreover, we identify a sixth
      positive regulatory region that regulates IL-2Ralpha expression in cells treated
      with anti-CD3 + anti-CD28 as well as TGF-beta and show that this region contains
      binding sites for Smad3, AP-1, and cAMP-responsive element-binding protein/ATF
      proteins. The importance of Smad complexes is indicated by impaired IL-2Ralpha
      induction by TGF-beta in CD4+ T cells from both Smad3-/- and Smad4-/- mice. Thus,
      we have identified a novel positive regulatory region in the IL-2Ralpha gene that
      mediates TGF-beta-dependent induction of the gene. These findings have
      implications related to IL-2Ralpha expression on activated T cells and regulatory
      T cells.

PMID- 16087672
TI  - Normal and cystic fibrosis airway surface liquid homeostasis. The effects of
      phasic shear stress and viral infections.
AB  - Mammalian airways normally regulate the volume of a thin liquid layer, the
      periciliary liquid (PCL), to facilitate the mucus clearance component of lung
      defense. Studies under standard (static) culture conditions revealed that normal
      airway epithelia possess an adenosine-regulated pathway that blends Na+
      absorption and Cl- secretion to optimize PCL volume. In cystic fibrosis (CF), the
      absence of CF transmembrane conductance regulator results in a failure of
      adenosine regulation of PCL volume, which is predicted to initiate mucus stasis
      and infection. However, under conditions that mimic the phasic motion of the lung
      in vivo, ATP release into PCL was increased, CF ion transport was rebalanced, and
      PCL volume was restored to levels adequate for lung defense. This ATP signaling
      system was vulnerable, however, to insults that trigger CF bacterial infections,
      such as viral (respiratory syncytial virus) infections, which up-regulated
      extracellular ATPase activity and abolished motion-dependent ATP regulation of CF
      PCL height. These studies demonstrate (i) how the normal coordination of opposing
      ion transport pathways to maintain PCL volume is disrupted in CF, (ii) the
      hitherto unknown role of phasic motion in regulating key aspects of normal and CF
      innate airways defense, and (iii) that maneuvers directed at increasing motion
      induced nucleotide release may be therapeutic in CF patients.

PMID- 16087673
TI  - Copper stress causes an in vivo requirement for the Escherichia coli disulfide
      isomerase DsbC.
AB  - In Escherichia coli, the periplasmic disulfide oxidoreductase DsbA is thought to
      be a powerful but nonspecific oxidant, joining cysteines together the moment they
      enter the periplasm. DsbC, the primary disulfide isomerase, likely resolves
      incorrect disulfides. Given the reliance of protein function on correct disulfide
      bonds, it is surprising that no phenotype has been established for null mutations
      in dsbC. Here we demonstrate that mutations in the entire DsbC disulfide
      isomerization pathway cause an increased sensitivity to the redox-active metal
      copper. We find that copper catalyzes periplasmic disulfide bond formation under
      aerobic conditions and that copper catalyzes the formation of disulfide-bonded
      oligomers in vitro, which DsbC can resolve. Our data suggest that the copper
      sensitivity of dsbC- strains arises from the inability of the cell to rearrange
      copper-catalyzed non-native disulfides in the absence of functional DsbC. Absence
      of functional DsbA augments the deleterious effects of copper on a dsbC- strain,
      even though the dsbA- single mutant is unaffected by copper. This may indicate
      that DsbA successfully competes with copper and forms disulfide bonds more
      accurately than copper does. These findings lead us to a model in which DsbA may
      be significantly more accurate in disulfide oxidation than previously thought,
      and in which the primary role of DsbC may be to rearrange incorrect disulfide
      bonds that are formed during certain oxidative stresses.

PMID- 16087674
TI  - Prostaglandin I(2) production and cAMP accumulation in response to acidic
      extracellular pH through OGR1 in human aortic smooth muscle cells.
AB  - Ovarian cancer G-protein-coupled receptor 1 (OGR1) and GPR4 have recently been
      identified as proton-sensing or extracellular pH-responsive G-protein-coupled
      receptors stimulating inositol phosphate production and cAMP accumulation,
      respectively. In the present study, we found that OGR1 and GPR4 mRNAs were
      expressed in human aortic smooth muscle cells (AoSMCs). Acidic extracellular pH
      induced inositol phosphate production, a transient increase in intracellular
      Ca(2+) concentration ([Ca(2+)](i)), and cAMP accumulation in these cells. When
      small interfering RNAs (siRNAs) targeted for OGR1 and GPR4 were transfected to
      the cells, the acid-induced inositol phosphate production and [Ca(2+)](i)
      increase were markedly inhibited by the OGR1 siRNA but not by the GPR4 siRNA.
      Unexpectedly, the acid-induced cAMP accumulation was also largely inhibited by
      OGR1 siRNA but only slightly by GPR4 siRNA. Acidic extracellular pH also
      stimulated prostaglandin I2 (PGI(2)) production, which was again inhibited by
      OGR1 siRNA. The specific inhibitors for extracellular signal-regulated kinase
      kinase and cyclooxygenase attenuated the acid-induced PGI(2) production and cAMP
      accumulation without changes in the inositol phosphate production. A specific
      inhibitor of phospholipase C also inhibited the acid-induced cAMP accumulation.
      In conclusion, OGR1 is a major receptor involved in the extracellular acid
      induced stimulation of PGI(2) production and cAMP accumulation in AoSMCs. The
      cAMP accumulation may occur through OGR1-mediated stimulation of the
      phospholipase C/cyclooxygenase/PGI(2) pathway.

PMID- 16087675
TI  - Identification of three gp350/220 regions involved in Epstein-Barr virus invasion
      of host cells.
AB  - Epstein-Barr virus (EBV) invasion of B-lymphocytes involves EBV gp350/220 binding
      to B-lymphocyte CR2. The anti-gp350 monoclonal antibody (mAb)-72A1 Fab inhibits
      this binding and therefore blocks EBV invasion of target cells. However,
      gp350/220 regions interacting with mAb 72A1 and involved in EBV invasion of
      target cells have not yet been identified. This work reports three gp350/220
      regions, defined by peptide 11382, 11389, and 11416 sequences, that are involved
      in EBV binding to B-lymphocytes. Peptides 11382, 11389, and 11416 bound to CR2(+)
      but not to CR2(-) cells, inhibited EBV invasion of cord blood lymphocytes (CBLs),
      were recognized by mAb 72A1, and inhibited mAb 72A1 binding to EBV. Peptides
      11382 and 11416 binding to peripheral blood lymphocytes (PBLs) induced
      interleukin-6 protein synthesis in these cells, this phenomenon being inhibited
      by mAb 72A1. The same behavior has been reported for gp350/220 binding to PBLs.
      Anti-peptide 11382, 11389, and 11416 antibodies inhibited EBV binding and EBV
      invasion of PBLs and CBLs. Peptide 11382, 11389, and 11416 sequences presented
      homology with the C3dg regions coming into contact with CR2 (C3dg and gp350 bound
      to similar CR2 regions). These peptides could be used in designing strategies
      against EBV infection.

PMID- 16087676
TI  - A novel form of neurotensin post-translationally modified by arginylation.
AB  - A novel bioactive form of neurotensin post-translationally modified at a Glu
      residue was isolated from porcine intestine. Purification of the peptide was
      guided by detection of intracellular Ca2+ release in SK-N-SH neuroblastoma cells.
      Using high resolution accurate mass analysis on an ion trap Fourier transform
      mass spectrometer, the post-translational modification was identified as arginine
      linked to the gamma-carboxyl of Glu via an isopeptide bond, and we named the
      newly identified peptide "arginylated neurotensin" (R-NT, N-(neurotensin-C5-4
      yl)arginine). Although arginylation is a known modification of N-terminal amino
      groups in proteins, its presence at a Glu side chain is unique. The finding
      places neurotensin among the few physiologically active peptides that occur both
      in post-translationally modified and unmodified forms. Pharmacologically, we
      characterized R-NT for its ligand activity on three known neurotensin receptors,
      NTR1, -2, and -3, and found that R-NT has similar pharmacological properties to
      those of neurotensin, however, with a slightly higher affinity to all three
      receptors. We expressed the intracellular receptor NTR3 as a soluble protein
      secreted into the cell culture medium, which allowed characterization of its R-NT
      and neurotensin binding properties. The creation of soluble NTR3 also provides a
      potential tool for neutralizing neurotensin action in vivo and in vitro. We have
      shown that SK-N-SH neuroblastoma cells express NTR1 and NTR3 but not NTR2,
      suggesting that the Ca2+ mobilization elicited by R-NT is via NTR1.

PMID- 16087677
TI  - Plasmin- and thrombin-accelerated shedding of syndecan-4 ectodomain generates
      cleavage sites at Lys(114)-Arg(115) and Lys(129)-Val(130) bonds.
AB  - Syndecans are transmembranous heparan sulfate proteoglycans abundant in the
      surface of all adherent mammalian cells and involved in vital cellular functions.
      In this study, we found syndecan-1, -2, -3, and -4 to be constitutively expressed
      by human umbilical vein endothelial cells. The exposure of the ectodomains of
      syndecan-1 and -4 to the cell surface and their constitutive shedding into the
      extracellular compartment was measured by immunoassays. In the presence of
      plasmin and thrombin, shedding was accelerated and monitored by detection and
      identification of (35)S-labeled proteoglycans. To elucidate the cleavage site of
      the syndecan ectodomains, we used a cell-free in vitro system with enzyme and
      substrate as the only reactants. For this purpose, we constructed recombinant
      fusion proteins of the syndecan-1 and -4 ectodomain together with maltose-binding
      protein and enhanced yellow fluorescent protein as reporter proteins attached to
      the N and C termini via oligopeptide linkers. After protease treatment of the
      fusion proteins, the electrophoretically resolved split products were sequenced
      and cleavage sites of the ectodomain were identified. Plasmin generated cleavage
      sites at Lys(114) downward arrowArg(115) and Lys(129) downward arrowVal(130) in
      the ectodomain of syndecan-4. In thrombin proteolysates of the syndecan-4
      ectodomain, the cleavage site Lys(114) downward arrowArg(115) was also
      identified. The cleavage sites for plasmin and thrombin within the syndecan-4
      ectodomain were not present in the syndecan-1 ectodomain. Cleavage of the
      syndecan-1 fusion protein by thrombin occurred only at a control cleavage site
      (Arg downward arrowGly) introduced into the linker region connecting the
      ectodomain with the enhanced yellow fluorescent protein. Because both plasmin and
      thrombin are involved in thrombogenic and thrombolytic processes in the course of
      the pathogenesis of arteriosclerosis, the detachment of heparan sulfate-bearing
      ectodomains could be relevant for the development of arteriosclerotic plaques and
      recruitment of mononuclear blood cells to the plaque.

PMID- 16087678
TI  - Full-length p73alpha represses drug-induced apoptosis in small cell lung
      carcinoma cells.
AB  - The p73 gene, a member of the p53 family, encodes several variants through
      differential splicing and use of alternative promoters. At the NH2 terminus, two
      different promoters generate the full-length and the DeltaN isoforms, with or
      without the transactivating domain. At the COOH terminus, seven isoforms
      generated through alternative splicing have been cloned. Previous studies have
      demonstrated that DeltaNp73 isoforms exert a dominant-negative effect on p73 by
      blocking their transactivation activity and hence the ability to induce
      apoptosis. Considerable efforts are made to identify the functional diversity of
      the COOH-terminal p73 variants. In this study, we found that p73alpha inhibited
      drug-induced apoptosis in small cell lung carcinoma cells, whereas p73beta
      promoted it. p73alpha prevented Bax activation, mitochondrial dysfunction, and
      caspase activation. In addition, p73alpha was also able to reduce apoptosis
      induced by the BH3-only protein PUMA (p53 up-regulated modulator of apoptosis).
      Furthermore, we discovered that p73alpha is able to inhibit the pro-apoptotic
      effect of p73beta, demonstrating the existence of equilibrium between these two
      p73 isoforms. In conclusion, the reported overexpression of p73alpha in certain
      tumor types, and our findings that p73alpha exerts anti-apoptotic functions,
      indicate a potential oncogenic activity for p73.

PMID- 16087680
TI  - Recruitment of nuclear factor Y to the inverted CCAAT element (ICE) by c-Jun and
      E1A stimulates basal transcription of the bone sialoprotein gene in osteosarcoma
      cells.
AB  - Bone sialoprotein (BSP), a major protein in the extracellular matrix of bone, is
      expressed almost exclusively by bone cells and by cancer cells that have a
      propensity to metastasize to bone. Previous studies have shown that v-src
      stimulates basal transcription of bsp in osteosarcoma (ROS 17/2.8) cells by
      targeting the inverted CCAAT element (ICE) in the proximal promoter. To identify
      possible downstream effectors of Src we studied the effects of the proto-oncogene
      c-jun, which functions downstream of Src, on basal transcription of bsp using
      transient transfection assays. Increased expression of endogenous c-Jun induced
      by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate and ectopic
      expression of c-Jun increased basal transcription of chimeric reporter constructs
      encompassing the proximal promoter by 1.5-3-fold in ROS 17/2.8 osteosarcoma
      cells, with more modest effects in a normal bone cell line, RBMC-D8. The effects
      of c-Jun were abrogated by mutations in the ICE box and by co-expression of
      dominant negative nuclear factor Y, subunit A (NF-YA). The increase in bsp
      transcription did not require phosphorylation of c-Jun and was not altered by
      trichostatin treatment or by ectopic expression of p300/CREB-binding protein
      (CBP) or mutated forms lacking histone acetyltransferase (HAT) activity.
      Similarly, ectopic expression of p300/CBP-associated factor (P/CAF), which
      transduces p300/CBP effects, or of HAT-defective P/CAF did not influence the c
      jun effects. Surprisingly, E1A, which competes with P/CAF binding to p300/CBP,
      also stimulated BSP transcription through NF-Y independently of c-jun, p300/CBP,
      and P/CAF. Collectively, these studies show that c-Jun and E1A regulate basal
      transcription of bsp in osteosarcoma cells by recruiting the NF-Y transcriptional
      complex to the ICE box in a mechanism that is independent of p300/CBP and P/CAF
      HAT activities.

PMID- 16087679
TI  - Identification of the surfactant protein A receptor 210 as the unconventional
      myosin 18A.
AB  - Mass spectrometric characterization of the surfactant protein A (SP-A) receptor
      210 (SP-R210) led to the identification of myosin (Myo) XVIIIA and nonmuscle
      myosin IIA. Antibodies generated against the unique C-terminal tail of MyoXVIIIA
      revealed that MyoXVIIIA, MyoIIA, and SP-R210 have overlapping tissue
      distribution, all being highly expressed in myeloid cells, bone marrow, spleen,
      lymph nodes, and lung. Western blot analysis of COS-1 cells stably transfected
      with either MyoXVIIIA or MyoIIA indicated that SP-R210 antibodies recognize
      MyoXVIIIA. Furthermore, MyoXVIIIA but not MyoIIA localized to the surface of COS
      1 cells, and most importantly, expression of MyoXVIIIA in COS-1 cells conferred
      SP-A binding. Western analysis of recombinant MyoXVIIIA domains expressed in
      bacteria mapped the epitopes of previously derived SP-R210 antibodies to the neck
      region of MyoXVIIIA. Antibodies raised against the neck domain of MyoXVIIIA
      blocked the binding of SP-A to macrophages. Together, these findings indicate
      that MyoXVIIIA constitutes a novel receptor for SP-A.

PMID- 16087681
TI  - Toward an assembly line for U7 snRNPs: interactions of U7-specific Lsm proteins
      with PRMT5 and SMN complexes.
AB  - The survival of motor neurons (SMN) complex mediates the assembly of small
      nuclear ribonucleoproteins (snRNPs) involved in splicing and histone RNA
      processing. A crucial step in this process is the binding of Sm proteins onto the
      SMN protein. For Sm B/B', D1, and D3, efficient binding to SMN depends on
      symmetrical dimethyl arginine (sDMA) modifications of their RG-rich tails. This
      methylation is achieved by another entity, the PRMT5 complex. Its pICln subunit
      binds Sm proteins whereas the PRMT5 subunit catalyzes the methylation reaction.
      Here, we provide evidence that Lsm10 and Lsm11, which replace the Sm proteins D1
      and D2 in the histone RNA processing U7 snRNPs, associate with pICln in vitro and
      in vivo without receiving sDMA modifications. This implies that the PRMT5 complex
      is involved in an early stage of U7 snRNP assembly and hence may have a second
      snRNP assembly function unrelated to sDMA modification. We also show that the
      binding of Lsm10 and Lsm11 to SMN is independent of any methylation activity.
      Furthermore, we present evidence for two separate binding sites in SMN for Sm/Lsm
      proteins. One recognizes Sm domains and the second one, the sDMA-modified RG
      tails, which are present only in a subset of these proteins.

PMID- 16087682
TI  - Functional effects of KCNJ11 mutations causing neonatal diabetes: enhanced
      activation by MgATP.
AB  - Recent studies have shown that heterozygous mutations in KCNJ11, which encodes
      Kir6.2, the pore-forming subunit of the ATP-sensitive potassium (K(ATP)) channel,
      cause permanent neonatal diabetes either alone (R201C, R201H) or in association
      with developmental delay, muscle weakness and epilepsy (V59G,V59M). Functional
      analysis in the absence of Mg2+, to isolate the inhibitory effects of ATP on
      Kir6.2, showed that both types of mutation reduce channel inhibition by ATP.
      However, in pancreatic beta-cells, K(ATP) channel activity is governed by the
      balance between ATP inhibition via Kir6.2 and Mg-nucleotide stimulation mediated
      by an auxiliary subunit, the sulphonylurea receptor SUR1. We therefore studied
      the MgATP sensitivity of KCNJ11 mutant K(ATP) channels expressed in Xenopus
      oocytes. In contrast to wild-type channels, Mg2+ dramatically reduced the ATP
      sensitivity of heterozygous R201C, R201H, V59M and V59G channels. This effect was
      predominantly mediated via the nucleotide-binding domains of SUR1 and resulted
      from an enhanced stimulatory action of MgATP. Our results therefore demonstrate
      that KCNJ11 mutations increase the current magnitude of heterozygous K(ATP)
      channels in two ways: by increasing MgATP activation and by decreasing ATP
      inhibition. They further show that the fraction of unblocked K(ATP) current at
      physiological MgATP concentrations correlates with the severity of the clinical
      phenotype.

PMID- 16087683
TI  - Deletions on mouse Yq lead to upregulation of multiple X- and Y-linked
      transcripts in spermatids.
AB  - Deletions on the mouse Y-chromosome long arm (MSYq) lead to teratozoospermia and
      in severe cases to infertility. We find that the downstream transcriptional
      changes in the testis resulting from the loss of MSYq-encoded transcripts involve
      upregulation of multiple X- and Y-linked spermatid-expressed genes, but not
      related autosomal genes. Therefore, this indicates that in normal males, there is
      a specific repression of X and Y (gonosomal) transcription in post-meiotic cells,
      which depends on MSYq-encoded transcripts. Together with the known sex ratio skew
      in favour of females in the offspring of fertile MSYqdel males, this strongly
      suggests the existence of an intragenomic conflict between X- and Y-linked genes.
      Two potential antagonists in this conflict are the X-linked multicopy gene Xmr
      and its multicopy MSYq-linked relative Sly, which are upregulated and
      downregulated, respectively, in the testes of MSYqdel males. Xmr is also
      expressed during meiotic sex chromosome inactivation (MSCI), indicating a link
      between the MSCI and the MSYq-dependent gonosomal repression in spermatids. We
      therefore propose that this repression and MSCI itself are evolutionary
      adaptations to maintain a normal sex ratio in the face of X/Y antagonism.

PMID- 16087684
TI  - Rad50 depletion impacts upon ATR-dependent DNA damage responses.
AB  - The Mre11/Rad50/NBS1 (MRN) complex is mutated in inherited genomic instability
      syndromes featuring cancer predisposition, mental retardation and
      immunodeficiency. It functions both in DNA double-strand break repair and in
      controlling the ataxia telangiectasia mutated (ATM) kinase during the response to
      these lesions. Patients inheriting homozygosity for an NBS1 hypomorphic allele
      display reduced phosphorylation of signaling factors such as Chk1, but not of
      chromatin-associated factor H2AX, after stresses that activate the ATM-related
      kinase, ATR. Therefore, we tested whether MRN has a global controlling role over
      the ATR kinase through the study of MRN deficiencies generated via RNA
      interference. We show for the first time that MRN is required for ATR-dependent
      phosphorylation of structural maintenance of chromosomes 1 (Smc1), which acts
      within chromatin to ensure sister chromatid cohesion and to effect several DNA
      damage responses. We have uncovered novel phenotypes caused by MRN deficiency
      that support a functional link between this complex, ATR and Smc1, including
      hypersensitivity to UV exposure, a defective UV responsive intra-S phase
      checkpoint and a specific pattern of genomic instability. In addition, certain
      ATR-dependent responses do not require MRN. These studies demonstrate that there
      is indeed a controlling role for MRN over the ATR kinase and have established
      that the downstream events under this control are broad, including both chromatin
      associated and diffuse signaling factors, but may not be universal. These studies
      contribute to our understanding of the central role that MRN plays in damage
      detection and signaling, which serve to maintain genomic stability and resist
      neoplastic transformation.

PMID- 16087685
TI  - Aberrant recombination involving the granzyme locus occurs in Atm-/- T-cell
      lymphomas.
AB  - Ataxia telangiectasia (A-T) is an autosomal recessive disease caused by loss of
      function of the serine/threonine protein kinase ATM (ataxia telangiectasia
      mutated). A-T patients have a 250-700-fold increased risk of developing lymphomas
      and leukemias which are typically highly invasive and proliferative. In addition,
      a subset of adult acute lymphoblastic leukemias and aggressive B-cell chronic
      lymphocytic leukemias that occur in the general population show loss of
      heterozygosity for ATM. To define the specific role of ATM in lymphomagenesis, we
      studied T-cell lymphomas isolated from mice with mutations in ATM and/or p53
      using cytogenetic analysis and mRNA transcriptional profiling. The analyses
      identified genes misregulated as a consequence of the amplifications, deletions
      and translocation events arising as a result of ATM loss. A specific recurrent
      disruption of the granzyme gene family locus was identified resulting in an
      aberrant granzyme B/C fusion product. The combined application of cytogenetic and
      gene expression approaches identified specific loci and genes that define the
      pathway of initiation and progression of lymphoreticular malignancies in the
      absence of ATM.

PMID- 16087686
TI  - Ribosomal frameshifting on MJD-1 transcripts with long CAG tracts.
AB  - The expanded CAG tract diseases are a heterogeneous group of late-onset
      neurodegenerative disorders characterized by the accumulation of insoluble
      protein material and premature neuronal cell death. Recent work has provided
      support for several mechanisms that may account for neurodegeneration, but no
      unifying mechanism has emerged. We have previously demonstrated that in SCA3, the
      expanded CAG tract in the MJD-1 transcript is prone to frameshifting, which may
      lead to the production of polyalanine-containing proteins. To further examine the
      occurrence of frameshifting and understand its mechanism and possible role in
      pathogenesis, a cellular model was established. We show that this phenomenon
      results from ribosomal slippage to the -1 frame exclusively, that ribosomal
      frameshifting depends on the presence of long CAG tracts and that polyalanine
      frameshifted proteins may enhance polyglutamine-associated toxicity, possibly
      contributing to pathogenesis. Finally, we present evidence that anisomycin, a
      ribosome-interacting drug that reduces -1 frameshifting, also reduces toxicity,
      suggesting a new therapeutic opportunity for these disorders.

PMID- 16087687
TI  - Regression models for twin studies: a critical review.
AB  - Twin studies have long been recognized for their value in learning about the
      aetiology of disease and specifically for their potential for separating genetic
      effects from environmental effects. The recent upsurge of interest in life-course
      epidemiology and the study of developmental influences on later health has
      provided a new impetus to study twins as a source of unique insights. Twins are
      of special interest because they provide naturally matched pairs where the
      confounding effects of a large number of potentially causal factors (such as
      maternal nutrition or gestation length) may be removed by comparisons between
      twins who share them. The traditional tool of epidemiological 'risk factor
      analysis' is the regression model, but it is not straightforward to transfer
      standard regression methods to twin data, because the analysis needs to reflect
      the paired structure of the data, which induces correlation between twins. This
      paper reviews the use of more specialized regression methods for twin data, based
      on generalized least squares or linear mixed models, and explains the
      relationship between these methods and the commonly used approach of analysing
      within-twin-pair difference values. Methods and issues of interpretation are
      illustrated using an example from a recent study of the association between birth
      weight and cord blood erythropoietin. We focus on the analysis of continuous
      outcome measures but review additional complexities that arise with binary
      outcomes. We recommend the use of a general model that includes separate
      regression coefficients for within-twin-pair and between-pair effects, and
      provide guidelines for the interpretation of estimates obtained under this model.

PMID- 16087688
TI  - Genetic biases in using 'Mendelian randomization' to compare transplantation with
      chemotherapy.

PMID- 16087690
TI  - Limitations of the syndromic approach in South Asia.

PMID- 16087689
TI  - Enhanced Na-Li countertransport: a marker of inherited susceptibility to type 2
      diabetes.
AB  - Introduction The association between type 2 diabetes and hypertension has long
      been described, but the mechanisms remain unclear. Na-Li countertransport (Na-Li
      CT) activity is viewed as a marker of inherited pre-disposition to hypertension,
      especially if associated with other metabolic abnormalities. Aim To evaluate
      whether enhanced Na-Li CT activity is a predictor of type 2 diabetes. METHODS:
      Study participants were 2167 men and women, 30-70 years. Na-Li CT activity,
      glucose, HDL cholesterol, blood pressure, height, and weight were measured. Six
      years incidence of diabetes (WHO) was assessed. RESULTS: Baseline Na-Li CT
      activity was significantly higher for people who developed diabetes at follow-up
      (n = 101) than for those who remained non-diabetic (364 +/- 184 vs 300 +/- 150
      micromol/l RBC/h, P < 0.001). This finding was confirmed after correction for
      obesity, hypertension, and blood glucose. Six years' incidence of diabetes
      increased across tertiles of baseline Na-Li CT activity--from 2 to 7%--with a
      significant linear trend (P < 0.001). In multivariate analyses Na-Li CT is a
      significant predictor of diabetes independent of age, BMI, HDL cholesterol,
      hypertension, and plasma glucose; based on exponentiation of the regression
      coefficient Na-Li CT higher by 154 micromol (i.e. 1 SD of the population mean)
      was associated with a 36% greater risk of incident diabetes. CONCLUSIONS:
      Prospective data from the present study show for the first time enhanced Na-Li CT
      activity is a significant predictor of development of diabetes in adults, thus
      suggesting that it could be viewed as a pre-clinical, possibly genetic, marker of
      inherited susceptibility to type 2 diabetes.

PMID- 16087691
TI  - The relationship between active living and health-related quality of life: income
      as a moderator.
AB  - This study used a moderator model to examine the relationship between active
      living and the physical components of health-related quality of life [i.e.
      overall physical component of quality of life (PQOL), physical functioning and
      ability to fulfill physical role] among a randomly selected sample of rural
      residents (n = 407) from the Midwestern US. Results showed that active living was
      associated with greater increases in health-related quality of life for those
      reporting lower income. The effect size of the relationship between active living
      and the PQOL for the low-income group was over 2 times the effect size for the
      high-income group. For physical functioning, the effect size of active living for
      the low-income group was greater than 3 times the effect size for the high-income
      group. Although active living behaviors have been demonstrated to be less
      prevalent among those of low socioeconomic status, this group may have the most
      to gain from these activities. Findings highlight the need for increased and
      specifically targeted promotion of active living interventions.

PMID- 16087692
TI  - The European Smoking prevention Framework Approach (ESFA): effects after 24 and
      30 months.
AB  - The European Smoking Prevention Framework Approach (ESFA) study in six countries
      tested the effects of a comprehensive smoking prevention approach after 24 (T3; N
      = 10,751) and 30 months (T4; N = 9,282). The programme targeted four levels, i.e.
      adolescents in schools, school policies, parents and the community. In Portugal,
      12.4% of the T1 non-smokers in the control group had started smoking at T4
      compared to 7.9% of the experimental group. Smoking onset in the experimental
      group was thus 36% lower. In Finland, 32.4% of the T1 non-smokers started smoking
      compared to 27.6% of the experimental group, implying a 15% lower onset in the
      experimental group. In Spain, 33.0% of the T1 non-smokers in the control group
      had started smoking, compared to 29.1% of the experimental group, implying a 12%
      lower onset. In The Netherlands, the ESFA programme was effective for non-native
      adolescents with 11.4% new weekly smokers compared to 19.9% in the control group.
      An opposite effect was found in native Dutch adolescents with 19.0% new weekly
      smokers in the comparison group compared to 24.0% new smokers in the experimental
      group. Future programmes should use more standardized ways to assess process
      evaluations and should assess which elements are responsible for behavioral
      effects.

PMID- 16087693
TI  - A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed
      small-cell lung cancer: a CALGB and NCCTG study.
AB  - BACKGROUND: The aim of the present study was to evaluate the clinical activity of
      imatinib mesylate in patients with recurrent and refractory c-kit-expressing
      small-cell lung cancer. PATIENTS AND METHODS: Patients with c-kit-expressing SCLC
      (> or =1+ by immunohistochemistry) were enrolled in two groups. Arm A included
      patients with disease progression <3 months and arm B included patients with
      disease progression > or =3 months after previous treatment. Imatinib was
      administered at a dose of 400 mg b.i.d. continuously, with a cycle length of 28
      days. A single stage Simon design with a planned interim analysis was used to
      evaluate the 16-week progression free rate in each arm. RESULTS: A total of 29
      evaluable patients were entered into the study (seven in arm A, median age 68; 22
      in arm B, median age 64.5). Median number of treatment cycles was one in both
      arms. Grade 3+ non-hematologic adverse events were seen in 15 (52%) patients,
      with nausea, vomiting, dyspnea, fatigue, anorexia and dehydration each occurring
      in at least 10% of patients. Median survival was 3.9 and 5.3 months and median
      time to progression was 1 and 1.1 months for arms A and B, respectively.
      Enrollment to arm A was temporarily suspended prior to reaching interim analysis
      due to striking early disease progression (29%), early deaths (29%) and patient
      refusal (42%). No objective responses and no confirmed stable disease > or =6
      weeks were seen in either arm. Accrual was permanently terminated to both arms as
      only one patient was progression-free at 16 weeks. CONCLUSION: Imatinib failed to
      demonstrate any clinical activity in spite of patient selection for c-kit
      expressing SCLC. Our results strengthen the collective evidence that prediction
      of efficacy of novel therapeutic agents based on target expression, rather than
      pathway activation (for example, through activating mutations), may not be a
      valid paradigm for drug development.

PMID- 16087694
TI  - Prognostic significance of magnetic resonance imaging of bone marrow in
      previously untreated patients with multiple myeloma.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has been a useful technique for the
      assessment of patients with multiple myeloma (MM). We evaluated the prognostic
      significance of different MRI patterns in symptomatic patients with MM. PATIENTS
      AND METHODS: A total of 142 symptomatic MM patients underwent MRI before
      treatment. MRI patterns of involvement were correlated with known prognostic
      variables, including the International Staging System (ISS), response to
      treatment and survival. RESULTS: Focal marrow lesions were identified in 50% of
      patients, diffuse marrow replacement in 28%, a variegated pattern in 14% and
      normal pattern in 8%. When patients with the diffuse pattern were compared with
      patients with the other MRI patterns, they had features of more advanced disease
      such as higher ISS, anemia, hypercalcemia, elevated lactate dehydrogenase and
      extensive marrow plasmacytosis. Response rate was similar among patients with
      different MRI patterns. Median survival was 24 months for patients with the
      diffuse pattern, 51 months for those with the focal pattern, 52 months for those
      with the variegated pattern and 56 months for patients with the normal pattern (P
      = 0.001). The presence or absence of a diffuse MRI pattern separated patients
      with ISS stages I and II into two subgroups with significantly different survival
      times of 28 months and 61 months, respectively (P = 0.01). Furthermore, a diffuse
      MRI pattern predicted inferior outcome regardless of whether or not patients had
      received high-dose therapy with autologous stem cell transplantation. CONCLUSION:
      Diffuse marrow replacement on MRI adds to the evaluation of patients with
      multiple myeloma and their management.

PMID- 16087695
TI  - Introducing the BECT (biologically enhanced cytotoxic treatment) concept in
      cancer treatment.

PMID- 16087696
TI  - A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients
      with unresectable or metastatic pancreatic cancer.
AB  - BACKGROUND: This randomized phase III study compared the overall survival (OS) of
      pemetrexed plus gemcitabine (PG) versus standard gemcitabine (G) in patients with
      advanced pancreatic cancer. PATIENTS AND METHODS: Patients with unresectable
      locally advanced or metastatic pancreatic cancer and no prior systemic therapy
      (including 5-fluorouracil as a radiosensitizer) were randomized to receive either
      1,250 mg/m(2) gemcitabine on days 1 and 8 plus pemetrexed 500 mg/m(2) after
      gemcitabine on day 8 (PG arm) of each 21-day cycle, or gemcitabine 1,000 mg/m(2)
      on days 1, 8 and 15 of each 28-day cycle (G arm). RESULTS: Five hundred and sixty
      five patients with well-balanced baseline characteristics were randomly assigned
      (283 PG, 282 G). OS was not improved on the PG arm (6.2 months) compared with the
      G arm (6.3 months) (P=0.8477). Progression-free survival (3.9 versus 3.3 months;
      P=0.1109) and time to treatment failure (3 versus 2.2 months; P=0.2680) results
      were similar. Tumor response rate (14.8% versus 7.1%; P=0.004) was significantly
      better on the PG arm. Grade 3 or 4 neutropenia (45.1% versus 12.8%),
      thrombocytopenia (17.9% versus 6.2%), anemia (13.9% versus 2.9%), febrile
      neutropenia (9.9% versus 0.4%; all P <0.001) and fatigue (15% versus 6.6%;
      P=0.002) were significantly more common on the PG arm. Four treatment-related
      deaths occurred on the PG arm and none in the G arm. CONCLUSIONS: Pemetrexed plus
      gemcitabine therapy did not improve OS. Single-agent gemcitabine remains the
      standard of care for advanced pancreatic cancer.

PMID- 16087697
TI  - Clinical and immunological aspects of HLA class I deficiency.
AB  - Human leukocyte antigen (HLA) class I deficiency is a rare disease with
      remarkable clinical and biological heterogeneity. The spectrum of possible
      manifestations extends from the complete absence of symptoms to life-threatening
      disease conditions. It is usually diagnosed when HLA class I serological typing
      is unsuccessful; flow cytometric studies then reveal a severe reduction in the
      cell surface expression of HLA class I molecules (90-99% reduction compared to
      normal cells). In most cases to date, this low expression is due to a homozygous
      inactivating mutation in one of the two subunits of the transporter associated
      with antigen processing (TAP), critically involved in the peptide loading of HLA
      class I molecules. Although asymptomatic cases have been described, TAP
      deficiencies are usually characterized by chronic bacterial infections of the
      upper and lower airways, evolving to bronchiectasis, and in half of the cases,
      also skin ulcers with features of a chronic granulomatous inflammation. Despite
      the defect in HLA class-I-mediated presentation of viral antigens to cytotoxic T
      cells, the patients do not suffer from severe viral infections, presumably
      because of other efficient antiviral defence mechanisms such as antibodies, non
      HLA-class-I-restricted cytotoxic effector cells and CD8+ T-cell responses to TAP
      independent antigens. Treatment is at present exclusively symptomatic, and should
      particularly focus on the prevention of bronchiectasis, which requires early
      detection.

PMID- 16087698
TI  - B-type natriuretic peptide: a simple new test to identify coronary artery
      disease?
AB  - A common key question in clinical medicine is whether coronary artery disease
      (CAD) is present in a patient. This applies not only to patients with symptomatic
      chest pain, but also to those at high risk of sudden unexpected death due to
      asymptomatic CAD, such as diabetics. In both groups of patients, it would be of
      great benefit if a simple blood test could identify those most likely to have
      CAD. Such individuals could then be selected for more definitive but more
      invasive tests for CAD, such as angiography, exercise testing, etc. In addition
      to its established role in diagnosing heart failure, it appears that BNP may
      fulfil this function of pre-screening for both symptomatic and asymptomatic CAD.
      We review the evidence for this new prospect, which has the potential to reduce
      cardiac deaths by using a simple blood test to better target cardioprotective
      strategies to those who most need them.

PMID- 16087699
TI  - Anti-AIDS agents 65: investigation of the in vitro oxidative metabolism of 3',4'
      Di-O-(-)-camphanoyl-(+)-cis-khellactone derivatives as potent anti-hiv agents.
AB  - 3',4'-Di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) is a synthetic khellactone
      ester that exhibits potent in vitro anti-human immunodeficiency virus (HIV)
      activity with a mechanism distinct from clinically used anti-HIV agents. Several
      series of mono- and di-substituted DCK derivatives (DCKs) have previously been
      synthesized, and their structure-activity relationships are well established. To
      optimize DCK as a drug lead and to guide further structural modifications,
      metabolic stabilities and metabolite structures were analyzed. In vitro metabolic
      stabilities of DCKs in human liver microsomes were assessed using high
      performance liquid chromatography (HPLC) with UV detection to establish structure
      metabolism relationships (SMRs). HPLC coupled with ion trap mass spectrometry was
      used to identify the metabolite structures. The results indicated that DCKs
      undergo rapid oxidation on the lipophilic camphanoyl moieties and the
      substituents on the khellactone do not alter the rate or the metabolic pathways
      for this compound type. Our SMR and metabolite analysis study suggested that the
      two camphanoyl ester moieties are the determinants of the low metabolic stability
      and that structural alteration in the two esters may be necessary to improve
      metabolic profiles of DCKs.

PMID- 16087700
TI  - A comprehensive analysis of six dihydroflavonol 4-reductases encoded by a gene
      cluster of the Lotus japonicus genome.
AB  - Dihydroflavonol 4-reductase (DFR) is the first committed enzyme of the
      anthocyanin and condensed tannin pathways. Several DFR cDNAs have been cloned,
      and different specificities of DFR isozymes in the substrate hydroxylation
      patterns have been reported, but only fragmentary knowledge of DFR gene
      organization is available. Reported here is a comprehensive analysis of DFRs of a
      model legume, Lotus japonicus. A total of five DFR genes were found to form a
      cluster within a 38 kb region in the L. japonicus genome, whereas six cDNAs,
      including two splicing variants resulting from a transversion at a splicing
      acceptor site, were cloned. All the genes were expressed, with different organ
      specificities, in the mature plant. Three of the DFR proteins heterologously
      expressed in Escherichia coli showed catalytic activity, and their substrate
      preferences agreed with the variation of a specific active site residue (Asp or
      Asn) reported to control the specificity. The hydroxylation patterns of
      anthocyanidins and condensed tannin units in the stems did not reflect the
      substrate specificity of the expressed isozymes, implying complex regulation
      mechanisms in the biosynthesis. The two splicing variants and one DFR with Ser at
      the specificity-controlling position failed to show the activity, but a revertant
      protein replacing the unusual splicing restored the activity. The phylogenetic
      tree, constructed with known DFR sequences, showed evolutionary divergence of
      some of the DFR genes prior to the plant speciation. This work affords the basis
      for genetic and biochemical studies on the diversity of DFR and the flavonoid
      products.

PMID- 16087701
TI  - Recognition and envelope translocation of chloroplast preproteins.
AB  - Plastids are a diverse group of plant organelles that perform essential functions
      including important steps in many biosynthetic pathways. Chloroplasts are the
      best characterized type of plastid, and constitute the site of oxygenic
      photosynthesis in plants, a process essential to all higher life forms. It is
      well established that the majority (>90%) of chloroplast proteins are nucleus
      encoded and must be post-translationally imported into these envelope-bound
      compartments. Most nucleus-encoded chloroplast proteins are translated in
      precursor form on cytosolic ribosomes, targeted to the chloroplast surface, and
      then imported across the double-membrane envelope by translocons in the outer and
      inner envelope membranes of the chloroplast, termed TOC and TIC, respectively.
      Recently, significant progress has been made in our understanding of how proteins
      are targeted to the chloroplast surface and translocated across the chloroplast
      envelope into the stroma. Evidence suggesting the existence of multiple import
      pathways at the outer envelope membrane for different classes of precursor
      proteins has been presented. These pathways appear to utilize similar TOC
      complexes equipped with different combinations of homologous GTPase receptors,
      providing preprotein recognition specificity.

PMID- 16087702
TI  - Aberrant gata-3 expression in human pancreatic cancer.
AB  - Gata-3 has been shown to specifically alter its expression patterns in different
      types of cancers. Recent evidence suggests that an interference of Gata-3 exists
      in the TGF-beta signaling pathway. To determine the role of Gata-3 in pancreatic
      cancer, pancreatic cancer samples were analyzed in comparison to normal
      pancreatic tissues. Furthermore, four different pancreatic cancer cell lines with
      different alterations of the TGF-beta pathway were studied. To evaluate if a
      potential relationship with TGF-beta signaling pathway exists, we correlated mRNA
      expression levels with the expression of TGF-betas, TGF-beta receptors, and Smad
      3. Finally, we analyzed the influence of TGF-beta on Gata-3 expression in vitro.
      All pancreatic cancer samples demonstrated a marked overexpression of Gata-3 mRNA
      and protein. Immunohistochemical staining revealed strong and persistent
      cytoplasmic Gata-3 immunoreactivity in cancer cells. In an electrophoretic
      mobility shift assay, a disturbed nuclear translocation was confirmed. The
      expression of Gata-3 showed a significant correlation with the expression of TGF
      betas, TGF-beta receptors, and Smad-3. TGF-beta responsive cell lines showed a
      downregulation of Gata-3 mRNA upon TGF-beta exposure, whereas in TGF-beta
      unresponsive cell lines, Gata-3 mRNA expression persisted at high levels.
      Furthermore, strong specific upregulation of Gata-3 impaired nuclear
      translocation and its cooperative action with the TGF-beta pathway, suggesting
      that Gata-3 plays a central role in human pancreatic cancer.

PMID- 16087703
TI  - Tight junction proteins and perineurial cells in neurofibromas.
AB  - Cutaneous neurofibromas consist of axonal processes, Schwann cells, fibroblasts,
      perineurial cells, mast cells, and abundant extracellular matrix. The
      distribution and role of perineurial cells in neurofibromas has been uncertain,
      partly because there has not been a specific immunohistochemical marker for
      perineurial cells. In this study, tight junctions (TJs) of 16 neurofibromas from
      12 patients with neurofibromatosis type 1 (NF1) were analyzed using electron
      microscopy, immunohistochemistry, and Western transfer analysis. Cell-cell
      contacts with typical ultrastructural morphology of TJs were seen between
      adjacent perineurial cells surrounding the small nerves and between contacting
      perineurial cell processes embedded in tumor stroma. Immunohistochemistry showed
      expression of claudin-1, claudin-3, and ZO-1 in the intercellular junctions of a
      subpopulation of tumor cells. Occludin was present mainly in perineurium and
      claudin-5 localized to the blood vessels. Double immunolabelings were used to
      identify the cell types expressing claudin-1. The results showed that claudin-1
      positive cells were also positive for type IV collagen and epithelial membrane
      antigen but not for S-100 protein. This labeling pattern is consistent with
      perineurial cell phenotype. Using claudin-1 as a marker, our results showed that
      clusters of perineurial cells are distributed around the rudimentary nerves
      within cutaneous neurofibromas and at the periphery of some neurofibromas.

PMID- 16087704
TI  - Immunohistochemical localization of huntingtin-associated protein 1 in endocrine
      system of the rat.
AB  - Huntingtin-associated protein 1 (HAP1) was originally found to be localized in
      neurons and is thought to play an important role in neuronal vesicular
      trafficking and/or organelle transport. Based on functional similarity between
      neuron and endocrine cell in vesicular trafficking, we examined the expression
      and localization of HAP1 in the rat endocrine system using immunohistochemistry.
      HAP1-immunoreactive cells are widely distributed in the anterior lobe of the
      pituitary, scattered in the wall of the thyroid follicles, or clustered in the
      interfollicular space of the thyroid gland, exclusively but diffusely distributed
      in the medullae of adrenal glands, and selectively located in the pancreas
      islets. HAP1-containing cells were also found in the mucosa of stomach and small
      intestine with a distributive pattern similar to that of gastrointestinal
      endocrine cells. However, no HAP1-immunoreactive cell was found in the cortex of
      the adrenal gland, the testis, and the ovary. In the posterior lobe of the
      pituitary, HAP1-immunoreactive products were not detected in the cell bodies but
      in many stigmoid bodies, one kind of non-membrane-bound cytoplasmic organelle
      with a central or eccentric electron-lucent core. HAP1-immunoreactive stigmoid
      bodies were also found in the cytoplasm of endocrine cells in the thyroid gland,
      the medullae of adrenal gland, the pancreas islets, the stomach, and small
      intestine. The present study demonstrates that HAP1 is selectively expressed in
      part of the small peptide-, protein-, and amino-acid analog and derivative
      secreting endocrine cells but not in steroid hormone-secreting cells, suggesting
      that HAP1 is also involved in intracellular trafficking in certain types of
      endocrine cells.

PMID- 16087706
TI  - Expression of intermediate filament proteins and neuronal markers in the human
      fetal gut.
AB  - The human enteric nervous system (ENS) derives from migrating neural crest cells
      (NCC) and is structured into different plexuses embedded in the gastrointestinal
      tract wall. During development of the NCC, a rearrangement of various
      cytoskeletal intermediate filaments such as nestin, peripherin, or alpha
      internexin takes place. Although all are related to developing neurons, nestin is
      also used to identify neural stem cells. Until now, information about the
      prenatal development of the human ENS has been very restricted, especially
      concerning potential stem cells. In this study the expression of nestin,
      peripherin, and alpha-internexin, but also of neuronal markers such as protein
      gene product (PGP) 9.5 and tyrosine hydroxylase, were investigated in human fetal
      and postnatal gut. The tissue samples were rapidly removed and subsequently
      processed for immunohistochemistry or immunoblotting. Nestin could be detected in
      all samples investigated with the exception of the 9th and the 12th week of
      gestation (WOG). Although the neuronal marker PGP9.5 was coexpressed with nestin
      at the 14th WOG, this could no longer be observed at later time points. Alpha
      internexin and peripherin expression also did not appear before the 14th WOG,
      where they were coexpressed with PGP9.5. This study reveals that the intermediate
      filament markers investigated are not suitable to detect early neural crest stem
      cells.

PMID- 16087705
TI  - Osteoclast responses to lipopolysaccharide, parathyroid hormone and
      bisphosphonates in neonatal murine calvaria analyzed by laser scanning confocal
      microscopy.
AB  - Because the development and activity of osteoclasts in bone remodeling is
      critically dependent on cell-cell and cell-matrix interactions, we used laser
      confocal microscopy to study the response of osteoclasts to lipopolysaccharide
      (LPS; 10 microg/ml), parathyroid hormone (PTH; 10(-8) M), and bisphosphonates
      (BPs; 1-25 microM clodronate or 0.1-2.5 microM risedronate) in cultured neonatal
      calvaria. Following treatment with LPS or PTH (<48 hr), osteopontin (OPN) and the
      alphavbeta3 integrin were found colocalized with the actin ring in the sealing
      zone of actively resorbing osteoclasts. In contrast, non-resorbing osteoclasts in
      BP-treated cultures showed morphological abnormalities, including retraction of
      pseudopods and vacuolization of cytoplasm. In the combined presence of LPS and
      BP, bone-resorbing osteoclasts were smaller and the sealing zone diffuse,
      reflecting reduced actin, OPN, and beta3 integrin staining. Depth analyses of
      calvaria showed that the area of resorbed bone was filled with proliferating
      osteoblastic cells that stained for alkaline phosphatase, collagen type I, and
      bone sialoprotein, regardless of the presence of BPs. These studies show that
      confocal microscopy of neonatal calvaria in culture can be used to assess the
      cytological relationships between osteoclasts and osteoblastic cells in response
      to agents that regulate bone remodeling in situ, avoiding systemic effects that
      can compromise in vivo studies and artifacts associated with studies of isolated
      osteoclasts.

PMID- 16087707
TI  - Interactions of WASp, myosin-I, and verprolin with Arp2/3 complex during actin
      patch assembly in fission yeast.
AB  - Yeast actin patches are dynamic structures that form at the sites of cell growth
      and are thought to play a role in endocytosis. We used biochemical analysis and
      live cell imaging to investigate actin patch assembly in fission yeast
      Schizosaccharomyces pombe. Patch assembly proceeds via two parallel pathways: one
      dependent on WASp Wsp1p and verprolin Vrp1p converges with another dependent on
      class 1 myosin Myo1p to activate the actin-related protein 2/3 (Arp2/3) complex.
      Wsp1p activates Arp2/3 complex via a conventional mechanism, resulting in
      branched filaments. Myo1p is a weaker Arp2/3 complex activator that makes
      unstable branches and is enhanced by verprolin. During patch assembly in vivo,
      Wsp1p and Vrp1p arrive first independent of Myo1p. Arp2/3 complex associates with
      nascent activator patches over 6-9 s while remaining stationary. After reaching a
      maximum concentration, Arp2/3 complex patches move centripetally as activator
      proteins dissociate. Genetic dependencies of patch formation suggest that patch
      formation involves cross talk between Myo1p and Wsp1p/Vrp1p pathways.

PMID- 16087708
TI  - An AP-1/clathrin coat plays a novel and essential role in forming the Weibel
      Palade bodies of endothelial cells.
AB  - Clathrin provides an external scaffold to form small 50-100-nm transport
      vesicles. In contrast, formation of much larger dense-cored secretory granules is
      driven by selective aggregation of internal cargo at the trans-Golgi network; the
      only known role of clathrin in dense-cored secretory granules formation is to
      remove missorted proteins by small, coated vesicles during maturation of these
      spherical organelles. The formation of Weibel-Palade bodies (WPBs) is also cargo
      driven, but these are cigar-shaped organelles up to 5 mum long. We hypothesized
      that a cytoplasmic coat might be required to make these very different
      structures, and we found that new and forming WPBs are extensively, sometimes
      completely, coated. Overexpression of an AP-180 truncation mutant that prevents
      clathrin coat formation or reduced AP-1 expression by small interfering RNA both
      block WPB formation. We propose that, in contrast to other secretory granules,
      cargo aggregation alone is not sufficient to form immature WPBs and that an
      external scaffold that contains AP-1 and clathrin is essential.

PMID- 16087709
TI  - The origin recognition core complex regulates dendrite and spine development in
      postmitotic neurons.
AB  - The origin recognition complex (ORC) ensures exactly one round of genome
      replication per cell cycle through acting as a molecular switch that precisely
      controls the assembly, firing, and inactivation of the replication initiation
      machinery. Recent data indicate that it may also coordinate the processes of
      mitosis and cytokinesis and ensure the proper distribution of replicated genome
      to daughter cells. We have found that the ORC core subunits are highly expressed
      in the nervous system. They are selectively localized to the neuronal
      somatodendritic compartment and enriched in the membrane fraction. siRNA
      knockdown of ORC subunits dramatically reduced dendritic branch formation and
      severely impeded dendritic spine emergence. Expression of ORC ATPase motif
      mutants enhanced the branching of dendritic arbors. The ORC core complex thus
      appears to have a novel role in regulating dendrite and dendritic spine
      development in postmitotic neurons.

PMID- 16087710
TI  - Transcytosis of NgCAM in epithelial cells reflects differential signal
      recognition on the endocytic and secretory pathways.
AB  - NgCAM is a cell adhesion molecule that is largely axonal in neurons and apical in
      epithelia. In Madin-Darby canine kidney cells, NgCAM is targeted to the apical
      surface by transcytosis, being first inserted into the basolateral domain from
      which it is internalized and transported to the apical domain. Initial
      basolateral transport is mediated by a sequence motif (Y(33)RSL) decoded by the
      AP-1B clathrin adaptor complex. This motif is a substrate in vitro for tyrosine
      phosphorylation by p60src, a modification that disrupts NgCAM's ability to
      interact with clathrin adaptors. Based on the behavior of various NgCAM mutants,
      it appears that after arrival at the basolateral surface, the AP-1B interaction
      site is silenced by phosphorylation of Tyr(33). This slows endocytosis and
      inhibits basolateral recycling from endosomes, resulting in NgCAM transcytosis
      due to a cryptic apical targeting signal in its extracellular domain. Thus,
      transcytosis of NgCAM and perhaps other membrane proteins may reflect the spatial
      regulation of recognition by adaptors such as AP-1B.

PMID- 16087711
TI  - Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide
      range of response.
AB  - A long-standing paradox in the study of T cell antigen recognition is that of the
      high specificity-low affinity T cell receptor (TCR)-major histocompatibility
      complex peptide (MHCp) interaction. The existence of multivalent TCRs could
      resolve this paradox because they can simultaneously improve the avidity observed
      for monovalent interactions and allow for cooperative effects. We have studied
      the stoichiometry of the TCR by Blue Native-polyacrylamide gel electrophoresis
      and found that the TCR exists as a mixture of monovalent
      (alphabetagammaepsilondeltaepsilonzetazeta) and multivalent complexes with two or
      more ligand-binding TCRalpha/beta subunits. The coexistence of monovalent and
      multivalent complexes was confirmed by electron microscopy after label fracture
      of intact T cells, thus ruling out any possible artifact caused by detergent
      solubilization. We found that although only the multivalent complexes become
      phosphorylated at low antigen doses, both multivalent and monovalent TCRs are
      phosphorylated at higher doses. Thus, the multivalent TCRs could be responsible
      for sensing low concentrations of antigen, whereas the monovalent TCRs could be
      responsible for dose-response effects at high concentrations, conditions in which
      the multivalent TCRs are saturated. Thus, besides resolving TCR stoichiometry,
      these data can explain how T cells respond to a wide range of MHCp concentrations
      while maintaining high sensitivity.

PMID- 16087712
TI  - IL-4 receptor expression on CD8+ T cells is required for the development of
      protective memory responses against liver stages of malaria parasites.
AB  - IL-4 receptor (IL-4R)-deficient CD8+ T cells specific for the circumsporozoite
      protein of Plasmodium yoelii develop a severely impaired memory response after
      priming with parasites. Memory CD8+ T cells lacking the IL-4R are unable to
      establish a stable population residing in nonlymphoid organs, although they
      develop normally in lymphoid organs. Because memory cells from nonlymphoid organs
      disappear shortly after immunization, the protective antiparasitic activity of
      this T cell response also is lost. These results demonstrate that IL-4/IL-4R
      interactions on CD8+ T cells play a critical role in modulating the development
      and tissue distribution of memory cells induced by parasite immunization. They
      also indicate that memory cells residing in nonlymphoid tissues are critical for
      protective immunity against malaria parasites.

PMID- 16087713
TI  - Microsomal triglyceride transfer protein lipidation and control of CD1d on
      antigen-presenting cells.
AB  - Microsomal triglyceride transfer protein (MTP), an endoplasmic reticulum (ER)
      chaperone that loads lipids onto apolipoprotein B, also regulates CD1d
      presentation of glycolipid antigens in the liver and intestine. We show MTP RNA
      and protein in antigen-presenting cells (APCs) by reverse transcription
      polymerase chain reaction and by immunoblotting of mouse liver mononuclear cells
      and mouse and human B cell lines. Functional MTP, demonstrated by specific
      triglyceride transfer activity, is present in both mouse splenocytes and a CD1d
      positive mouse NKT hybridoma. In a novel in vitro transfer assay, purified MTP
      directly transfers phospholipids, but not triglycerides, to recombinant CD1d.
      Chemical inhibition of MTP lipid transfer does not affect major
      histocompatibility complex class II presentation of ovalbumin, but considerably
      reduces CD1d-mediated presentation of alpha-galactosylceramide (alpha-galcer) and
      endogenous antigens in mouse splenic and bone marrow-derived dendritic cells
      (DCs), as well as in human APC lines and monocyte-derived DCs. Silencing MTP
      expression in the human monocyte line U937 affects CD1d function, as shown by
      diminished presentation of alpha-galcer. We propose that MTP acts upstream of the
      saposins and functions as an ER chaperone by loading endogenous lipids onto
      nascent CD1d. Furthermore, our studies suggest that a small molecule inhibitor
      could be used to modulate the activity of NKT cells.

PMID- 16087714
TI  - IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water
      channel.
AB  - Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that
      selectively affects optic nerves and spinal cord. It is considered a severe
      variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but
      prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody
      (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds
      selectively to the aquaporin-4 water channel, a component of the dystroglycan
      protein complex located in astrocytic foot processes at the blood-brain barrier.
      NMO may represent the first example of a novel class of autoimmune channelopathy.

PMID- 16087715
TI  - Characterization of the early stages of thymic NKT cell development.
AB  - Upon reaching the mature heat stable antigen (HSA)low thymic developmental stage,
      CD1d-restricted Valpha14-Jalpha18 thymocytes undergo a well-characterized
      sequence of expansion and differentiation steps that lead to the peripheral
      interleukin-4/interferon-gamma-producing NKT phenotype. However, their more
      immature HSAhigh precursors have remained elusive, and it has been difficult to
      determine unambiguously whether NKT cells originate from a CD4+ CD8+ double
      positive (DP) stage, and when the CD4+ and CD4- CD8- double-negative (DN) NKT
      subsets are formed. Here, we have used a CD1d tetramer-based enrichment strategy
      to physically identify HSAhigh precursors in thymuses of newborn mice, including
      an elusive DPlow stage and a CD4+ stage, which were present at a frequency of
      approximately 10(-6). These HSAhigh DP and CD4+ stages appeared to be
      nondividing, and already exhibited the same Vbeta8 bias that characterizes mature
      NKT cells. This implied that the massive expansion of NKT cells is separated
      temporally from positive selection, but faithfully amplifies the selected TCR
      repertoire. Furthermore, we found that, unlike the DN gammadelta T cells, the DN
      NKT cells did not originate from a pTalpha-independent pathway bypassing the DP
      stage, but instead were produced during a short window of time from the
      conversion of a fraction of HSAlow NK1.1neg CD4 cells. These findings identify
      the HSAhigh CD4+ stage as a potential branchpoint between NKT and conventional T
      lineages and between the CD4 and DN NKT sublineages.

PMID- 16087716
TI  - Regulation of TCR delta and alpha repertoires by local and long-distance control
      of variable gene segment chromatin structure.
AB  - Murine Tcrd and Tcra gene segments reside in a single genetic locus and undergo
      recombination in CD4- CD8- (double negative [DN]) and CD4+ CD8+ (double positive
      [DP]) thymocytes, respectively. TcraTcrd locus variable gene segments are subject
      to complex regulation. Only a small subset of approximately 100 variable gene
      segments contributes substantially to the adult TCRdelta repertoire. Moreover,
      although most contribute to the TCRalpha repertoire, variable gene segments that
      are Jalpha proximal are preferentially used during primary Tcra recombination. We
      investigate the role of local chromatin accessibility in determining the
      developmental pattern of TcraTcrd locus variable gene segment recombination. We
      find variable gene segments to be heterogeneous with respect to acetylation of
      histones H3 and H4. Those that dominate the adult TCRdelta repertoire are
      hyperacetylated in DN thymocytes, independent of their position in the locus.
      Moreover, proximal variable gene segments show dramatic increases in histone
      acetylation and germline transcription in DP thymocytes, a result of super long
      distance regulation by the Tcra enhancer. Our results imply that differences in
      chromatin accessibility contribute to biases in TcraTcrd locus variable gene
      segment recombination in DN and DP thymocytes and extend the distance over which
      the Tcra enhancer can regulate chromatin structure to a remarkable 525 kb.

PMID- 16087717
TI  - Gene expression profile in rat pancreatic islet and RINm5F cells.
AB  - To clarify tissue-specificity of pancreatic beta cells, comparison of mRNA
      expression in various conditions of the tissue of multiple organisms is
      important. Although the developed methodologies for mRNA monitoring such as
      microarray, rely on the growth of dbEST (database of expressed sequence tag), a
      large number of unknown genes in the genome, especially in the rat, have not been
      shown to be expressed. In this study, we have established the first database of
      ESTs from rat pancreatic islet and RINm5F cells. Two cDNA libraries were
      constructed using mRNAs from rat pancreatic islet and RINm5F cells to cover a
      wider spectrum of expressed genes. Over 40,000 clones were randomly selected from
      the two libraries and partially sequenced. The sequences obtained were subjected
      to BLAST database analyses. This large-scale sequencing generated 40,710 3'-ESTs.
      Clustering analysis and homology search of nucleotide and peptide databases using
      both 3'- and 5'-ESTs revealed 10,406 non-redundant transcripts representing 4078
      known genes or homologs and 6328 unknown genes. To confirm actual expression, the
      unknown sequences were further subjected to dbEST search, resulting in the
      identification of 5432 significant matches to those from other sources.
      Interestingly, of the remaining sequences showing no match, 779 were found to be
      encoded by exon-intron organization in the corresponding genomic sequences,
      suggesting that these are newly found as actually expressed in this study. Since
      many genes are up- or down-regulated in differing conditions, applications of the
      expression profile should facilitate identification of the genes involved in cell
      specific functions in normal and disease states.

PMID- 16087718
TI  - Differential gene expression between Zucker Fatty rats and Zucker Diabetic Fatty
      rats: a potential role for the immediate-early gene Egr-1 in regulation of beta
      cell proliferation.
AB  - The beta-cell failure that characterises type 2 diabetes is likely to involve
      altered expression of many genes. We aimed to identify global changes in gene
      expression underlying beta-cell dysfunction in pre-diabetic Zucker Diabetic Fatty
      rat islets, followed by functional studies to verify our findings. Gene
      expression profiles in islets from 6-week-old Zucker Diabetic Fatty rats and
      Zucker Fatty rat controls were analysed using Affymetrix microarrays. Totally 977
      genes were found to be differentially regulated, comprising large groups of
      membrane and structural proteins, kinases, channels, receptors, transporters,
      growth factors and transcription factors. We are particularly interested in
      transcription factors, which can have profound effects on cellular function. Thus
      a subset of those with no role yet defined in the beta-cell was selected for
      further study namely the immediate-early gene Egr-1, PAG608, rCGR19 and mSin3b.
      Tissue specificity of these factors varied but interestingly Egr-1 expression was
      highly enriched in the pancreatic islet. To determine a possible role of Egr-1 in
      the beta-cell, Egr-1 expression in INS-1 cells was silenced using RNA
      interference (RNAi). Glucose-stimulated insulin secretion in these cells was then
      measured using ELISA and cell proliferation was measured by [(3)H]thymidine
      incorporation. Small interfering RNA (siRNA)-mediated silencing of the Egr-1 gene
      inhibited its induction by glucose but had no observable effect on glucose
      stimulated insulin secretion. However, Egr-1 gene silencing did inhibit
      proliferation of INS-1 cells in a glucose-independent manner. Our studies have
      revealed a role for Egr-1 and suggest that reduced Egr-1 gene expression may
      contribute to decreased beta-cell proliferation and the consequent beta-cell
      failure observed in the later stages of type 2 diabetes.

PMID- 16087719
TI  - Effects of glucagon-like peptide-1 and exendins on kinase activity, glucose
      transport and lipid metabolism in adipocytes from normal and type-2 diabetic
      rats.
AB  - Several kinases have been implicated in the metabolic response of human and rat
      myocytes to glucagon-like peptide-1 (GLP-1), exendin-4 (Ex-4) and exendin-9 (Ex
      9). We have investigated, in isolated rat adipocytes, the changes caused by GLP
      1, Ex-4 and Ex-9 compared with those provoked by insulin or glucagon, upon the
      activity of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB), p42/44
      MAP kinases (MAPKs) and p70s6 kinase (p70s6k), and the participation of these
      kinases and protein kinase C (PKC) in their action upon 2-deoxy-d-glucose uptake,
      lipolysis and lipogenesis. The study was conducted in normal rats, and extended
      to a streptozotocin-induced type-2 diabetic model (STZ-rats). The participation
      of distinct kinases was estimated by using potential kinase inhibitors, including
      wortmannin, PD98059, rapamycin, H-7 and RO31-8220. In normal rat adipocytes, GLP
      1 and both exendins share with insulin an increasing action upon the activity of
      all kinases studied (except PKB), PI3K, p44 and p42 MAPKs and possibly PKC, all
      being required for their stimulating effect upon glucose uptake. Ex-4 and Ex-9,
      like GLP-1 and insulin, have lipogenic action, while only Ex-4 shares with GLP-1
      its lipolytic effect which is antagonized by Ex-9. MAP kinases and PKC seem to
      have an essential role in the GLP-1 and Ex-4 lipolytic action, as does PI3K in
      that of Ex-4. An increase in PI3K and MAPKs activity for the lipogenic effect of
      Ex-4, Ex-9 and GLP-1 are required, and in the case of Ex-4 and Ex-9, a
      stimulation of p70s6k activity is also needed. In cells from STZ-rats the
      magnitude of the above parameters was, in general, comparable to that in normal
      animals, with some exceptions: basal PI3K activity and lipogenesis were higher,
      GLP-1, Ex-4 and Ex-9 failed to modify basal lipogenesis but increased PKB
      activity, insulin failed to affect the activity of MAPKs and the insulin-induced
      glucose uptake was impaired. The impaired insulin effects upon some of the
      variables in the STZ-rat, distinct from those of GLP-1 and exendins, adds
      knowledge to the mechanism of the beneficial action of GLP-1 and Ex-4 in diabetic
      states.

PMID- 16087720
TI  - High glucose-induced impairment in insulin secretion is associated with reduction
      in islet glucokinase in a mouse model of susceptibility to islet dysfunction.
AB  - Type 2 diabetes is characterized by islet dysfunction resulting in hyperglycemia,
      which can then lead to further deterioration in islet function. A possible
      mechanism for hyperglycemia-induced islet dysfunction is the accumulation of
      advanced glycation end products (AGE). The DBA/2 mouse develops pancreatic islet
      dysfunction when exposed to a high glucose environment and/or obesity-induced
      insulin resistance. To determine the biochemical cause of dysfunction, DBA/2 and
      C57BL/6 control islets were incubated in 11.1 mM or 40 mM glucose in the absence
      or presence of the AGE inhibitor aminoguanidine (AG) for 10 days. Basal (2.8 mM
      glucose) insulin release was increased in both DBA/2 and C57BL/6 islets incubated
      with 40 mM vs 11.1 mM glucose for 10 days. Chronic exposure to hyperglycemia
      decreased glucose (20 mM)-stimulated insulin secretion in DBA/2 but not in
      C57BL/6 islets. AG significantly increased fold-induced insulin release in high
      glucose cultured DBA/2 mouse islets, but did not affect C57BL/6 islet function.
      DBA/2 islet glucokinase was significantly reduced following 40 mM glucose
      culture, compared with 11.1 mM glucose cultured DBA/2 islets and 40 mM glucose
      cultured C57BL/6 islets. Incubation of islets with AG resulted in a normalization
      of DBA/2 islet glucokinase levels. In conclusion, chronic high glucose-induced
      increases in AGE can result in islet dysfunction and this is associated with
      reduced glucokinase levels in a mouse model with susceptibility to islet failure.

PMID- 16087721
TI  - Long-term inhibition of protein tyrosine kinase impairs electrophysiologic
      activity and a rapid component of exocytosis in pancreatic beta-cells.
AB  - Dysfunction of pancreatic beta-cells is a fundamental feature in the pathogenesis
      of type 2 diabetes. As insulin receptor signaling occurs via protein tyrosine
      kinase (PTK), we investigated the role of PTK activity in the etiology of beta
      cell dysfunction by inhibiting PTK activity in primary cultured mouse pancreatic
      beta-cells and INS-1 cells with genistein treatment over 24 h. Electrophysiologic
      recordings showed genistein treatment significantly attenuated ATP-sensitive K(+)
      (K(ATP)) and voltage-dependent Ca(2+) currents, and depolarized the resting
      membrane potential in primary beta-cells. When stimulated by high glucose,
      genistein-treated beta-cells exhibited a time delay of both depolarization and
      Ca(2+) influx, and were unable to fire action potentials, as well as displaying a
      reduced level of Ca(2+) influx and a loss of Ca(2+) oscillations.
      Semiquantitative PCR analysis revealed decreased expression of K(ATP) and L-type
      Ca(2+) channel mRNA in genistein-treated islets. PTK inhibition also
      significantly reduced the rapid component of secretory vesicle exocytosis, as
      indicated by membrane capacitance measurements, and this is likely to be due to
      the reduced Ca(2+) current amplitude in these cells. These results illustrate
      that compromised PTK activity contributes to pancreatic beta-cell dysfunction and
      may be involved in the etiology of type 2 diabetes.

PMID- 16087722
TI  - The Sp transcription factors are involved in the cellular expression of the human
      glucose-dependent insulinotropic polypeptide receptor gene and overexpressed in
      adrenals of patients with Cushing's syndrome.
AB  - The best characterized effect of glucose-dependent insulinotropic polypeptide
      (GIP) is its stimulatory effect on insulin secretion by pancreatic beta-cells.
      Recently, it was demonstrated that some cases of primary adrenal Cushing's
      syndrome were secondary to the ectopic expression of non-mutated GIP receptor
      (GIP-R) in bilateral adrenal hyperplasias or unilateral adrenal adenomas,
      resulting in food-dependent steroidogenesis. Using a human multiple-expression
      tissue array, GIP-R was found to be expressed in a large number of human adult
      and fetal tissues, but not in the adrenal gland. The analysis of the promoter
      region of human (h) GIP-R gene revealed six consensus sequences important in
      regulating the reporter gene activity and capable of binding to Sp1 and Sp3
      transcription factors. Data obtained by gene array and semi-quantitative RT-PCR
      showed an increase in the expression of Sp3 and CRSP9 (co-regulator of Sp1
      transcription factor, subunit 9) in the adrenal adenomas or bilateral
      macronodular hyperplasias of patients with GIP-dependent Cushing's syndrome; they
      were, however, also increased in some patients with non-GIP-dependent cortisol
      secreting adenomas or with ACTH-dependent Cushing's disease. This study
      represents the first step in our understanding of the mechanisms involved in the
      regulation of the expression of the hGIP-R gene.

PMID- 16087723
TI  - Proteomic exploration of pancreatic islets in mice null for the alpha2A
      adrenergic receptor.
AB  - The present studies extend recent findings that mice null for the alpha(2A)
      adrenergic receptor (alpha(2A) AR KO mice) lack suppression of exogenous
      secretagogue-stimulated insulin secretion in response to alpha(2) AR agonists by
      evaluating the endogenous secretagogue, glucose, ex vivo, and providing in vivo
      data that baseline insulin levels are elevated and baseline glucose levels are
      decreased in alpha(2A) AR KO mice. These latter findings reveal that the
      alpha(2A) AR subtype regulates glucose-stimulated insulin release in response to
      endogenous catecholamines in vivo. The changes in alpha(2A) AR responsiveness and
      resultant changes in insulin/glucose homeostasis encouraged us to utilize
      proteomics strategies to identify possible alpha(2A) AR downstream signaling
      molecules or other resultant changes due to perturbation of alpha(2A) AR
      expression. Although agonist stimulation of islets from wild type (WT) mice did
      not significantly alter islet protein profiles, several proteins were enriched in
      islets from alpha(2A) AR KO mice when compared with those from WT mice, including
      an enzyme participating in insulin protein processing. The present studies
      document the important role of the alpha(2A) AR subtype in tonic suppression of
      insulin release in response to endogenous catecholamines as well as exogenous
      alpha(2) agonists and provide insights into pleiotropic changes that result from
      loss of alpha(2A) AR expression and tonic suppression of insulin release.

PMID- 16087725
TI  - Cloning, expression and characterization of three types of 17beta-hydroxysteroid
      dehydrogenases from the Nile tilapia, Oreochromis niloticus.
AB  - In order to elucidate the roles of 17beta-HSDs in fish gonadal steroidogenesis,
      three types of 17beta-HSDs (17beta-HSD1, 17beta-HSD8 and putative 17beta-HSD12)
      were cloned and characterized from the Nile tilapia, Oreochromis niloticus. The
      cloned cDNAs of 17beta-HSD type 1, 8 and 12 were 1504, 1006 and 1930 bp long,
      with open reading frames encoding proteins of 289, 256 and 314 aminoacids,
      respectively. Tissue distribution pattern analyzed by RT-PCR and Northern blot
      showed that 17beta-HSD1 was dominantly expressed in the ovary, while the putative
      17beta-HSD12, one of the two duplicates found in fish, is a male specific enzyme
      and expressed exclusively in testis (detected by RT-PCR only). On the other hand,
      17beta-HSD8 was expressed in the brain, gill, heart, liver, intestine, gonad,
      kidney and muscle of both male and female. Enzymatic assays of the three types of
      17beta-HSDs were performed using recombinant proteins expressed in E. coli or HEK
      293 cells. Tilapia 17beta-HSD1 expressed in E. coli had the preference for
      NADP(H) as cofactor and could catalyze the inter-conversion between estrone and
      estradiol efficiently as well as the inter-conversion between androstenedione and
      testosterone, but less efficiently. Tilapia 17beta-HSD8 recombinant protein
      expressed in HEK 293 cells could catalyze the conversion of testosterone to
      androstenedione, as well as the inter-conversion between estrone and estradiol.
      However, the putative 17beta-HSD12 expressed in E. coli or in HEK 293 cells
      showed no conversion to any of the four substrates tested in this study. Based on
      enzyme characterization and tissue distribution, it is plausible to attribute
      crucial roles to 17beta-HSDs in the gonadal steroidogenesis of teleosts.

PMID- 16087724
TI  - Comparative enzymology of 11beta-hydroxysteroid dehydrogenase type 1 from six
      species.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1), catalyzing the
      intracellular activation of cortisone to cortisol, is currently considered a
      promising target to treat patients with metabolic syndrome; hence, there is
      considerable interest in the development of selective inhibitors. For preclinical
      tests of such inhibitors, the characteristics of 11beta-HSD1 from the commonly
      used species have to be known. Therefore, we determined differences in substrate
      affinity and inhibitor effects for 11beta-HSD1 from six species. The differences
      in catalytic activities with cortisone and 11-dehydrocorticosterone were rather
      modest. Human, hamster and guinea-pig 11beta-HSD1 displayed the highest catalytic
      efficiency in the oxoreduction of cortisone, while mouse and rat showed
      intermediate and dog the lowest activity. Murine 11beta-HSD1 most efficiently
      reduced 11-dehydrocorticosterone, while the enzyme from dog showed lower activity
      than those from the other species. 7-ketocholesterol (7KC) was stereospecifically
      converted to 7beta-hydroxycholesterol by recombinant 11beta-HSD1 from all species
      analyzed except hamster, which showed a slight preference for the formation of
      7alpha-hydroxycholesterol. Importantly, guinea-pig and canine 11beta-HSD1
      displayed very low 7-oxoreductase activities. Furthermore, we demonstrate
      significant species-specific variability in the potency of various 11beta-HSD1
      inhibitors, including endogenous compounds, natural chemicals and pharmaceutical
      compounds. The results suggest significant differences in the three-dimensional
      organization of the hydrophobic substrate-binding pocket of 11beta-HSD1, and they
      emphasize that species-specific variability must be considered in the
      interpretation of results obtained from different animal experiments. The
      assessment of such differences, by cell-based test systems, may help to choose
      the appropriate animal for safety and efficacy studies of novel potential drug
      candidates.

PMID- 16087726
TI  - Identification and characterization of a response element in the EGFR promoter
      that mediates transcriptional repression by 1,25-dihydroxyvitamin D3 in breast
      cancer cells.
AB  - Reduction of epidermal growth factor receptor (EGFR) mRNA and protein by 1,25
      dihydroxyvitamin D3 has been documented in MCF7, T47D, and BT549 breast cancer
      cells. In the present report, functional mapping of the EGFR promoter in BT549
      cells has revealed a sequence of DNA between nucleotide positions -536 and -478
      that resembles a consensus vitamin D response element (VDRE) and confers a
      vitamin D response upon both the homologous and a minimal heterologous promoter.
      In vitro footprinting and gel shift assays demonstrate the presence of an
      unidentified nuclear factor that is required for strong binding of the vitamin D
      receptor (VDR) to this putative VDRE. An Sp1 binding site was also identified in
      close proximity and shown to bind Sp1 from nuclear extract. Mutational analysis
      and functional studies using a minimal heterologous promoter provide evidence
      that the VDR in concert with an unknown nuclear partner mediates basal EGFR
      repression through displacement of Sp1 which is augmented in the presence of a
      ligand.

PMID- 16087727
TI  - The WT1 Wilms' tumor suppressor gene product interacts with estrogen receptor
      alpha and regulates IGF-I receptor gene transcription in breast cancer cells.
AB  - The IGF-I receptor (IGF-IR) has an important role in breast cancer development
      and progression. Previous studies have suggested that the IGF-IR gene is
      negatively regulated by a number of transcription factors with tumor suppressor
      activity, including the Wilms' tumor protein WT1. The present study was aimed at
      evaluating the hypothesis that IGF-IR gene transcription in breast cancer cells
      is under inhibitory control by WT1 and, furthermore, that the mechanism of action
      of WT1 involves functional and physical interactions with estrogen receptor-alpha
      (ERalpha). Results of transient coexpression experiments showed that all four
      predominant isoforms of WT1 (including or lacking alternatively spliced exons 5
      and 9) repressed IGF-IR promoter activity by 39-49%. To examine the potential
      interplay between WT1 and ERalpha in control of IGF-IR gene transcription we
      employed ER-depleted C4 cells that were generated by clonal selection of ER
      positive MCF-7 cells that were maintained in estrogen-free conditions. IGF-IR
      levels in C4 cells were approximately 43% of the values in MCF-7 cells whereas
      WT1 levels in C4 cells were 4.25-fold higher than in MCF-7. Triple cotransfection
      experiments using an ERalpha expression vector in the absence or presence of WT1
      expression vectors, along with an IGF-IR promoter reporter plasmid, revealed that
      ERalpha stimulated IGF-IR promoter activity whereas coexpression of WT1 abrogated
      the effect of ERalpha. In addition, co-immunoprecipitation experiments
      demonstrated a specific association between WT1 and ERalpha. Combined, our
      results suggest that WT1 suppresses IGF-IR gene transcription in breast cancer
      cells via a mechanism that involves protein-protein association with ERalpha. As
      a result of this interaction, the ability of ERalpha to transactivate the IGF-IR
      promoter is abrogated. These findings are consistent with a potential tumor
      suppressor role for WT1 in breast cancer and suggest that WT1 inactivation in
      tumoral cells may result in deregulated IGF-IR gene expression and enhanced
      mitogenic activation by locally produced and/or circulating IGFs.

PMID- 16087728
TI  - Pituitary homeobox 1 (Pitx1) stimulates rat LHbeta gene expression via two
      functional DNA-regulatory regions.
AB  - Luteinizing hormone (LH) plays a central role in the reproductive axis,
      stimulating both gonadal steroid biosynthesis and the development of mature
      gametes. Over the past decade, significant progress has been made in
      characterizing the transcription factors and associated DNA-regulatory sites
      which mediate expression of the LH beta-subunit gene (LHbeta). One of these
      factors, pituitary homeobox 1 (Pitx1), has been shown to stimulate LHbeta gene
      promoter activity, both alone and in synergy with the orphan nuclear receptor,
      steroidogenic factor-1 (SF-1), and the early growth response gene 1 (Egr-1).
      Prior reports have attributed the Pitx1 response to a cis-element located at
      position -101 in the rat LHbeta gene promoter. While investigating the role of
      Pitx1 in regulating rat LHbeta gene expression, we observed a small, but
      significant, residual Pitx1 response despite mutation or deletion of this site.
      In the studies presented here, we identify the presence of a second functional
      Pitx1 region spanning positions -73 to -52 in the rat LHbeta gene promoter. Based
      on electrophoretic mobility shift assay, Pitx1 binds to both the initially
      described 5'Pitx1 site as well as this putative 3'Pitx1 region. In transient
      transfection analysis, mutation of the LHbeta-3'Pitx1 site significantly blunted
      Pitx1 responsiveness, with elimination of the Pitx1 response in a construct
      containing mutations in both Pitx1 cis-elements. We also analyzed the importance
      of each of these Pitx1 sites for providing functional synergy with SF-1 and with
      Egr-1. We observed a markedly decreased synergistic response with mutation of the
      5'Pitx1 site with further loss following mutation of the 3'Pitx1 site. In
      contrast, functional interaction between Pitx1 and Egr-1 persisted with mutation
      of both Pitx1 regions. We conclude that Pitx1 stimulates the rat LHbeta gene
      promoter via two Pitx1 DNA-regulatory regions. These results further our
      understanding of the molecular mechanisms that regulate expression of this
      critical reproductive gene promoter.

PMID- 16087729
TI  - Differential regulation of agouti-related protein and neuropeptide Y in
      hypothalamic neurons following a stressful event.
AB  - Stress affects eating behaviour in rodents and humans, suggesting that the
      regulation of energy balance and the stress response are coupled physiological
      processes. Neuropeptide Y (NPY) and agouti-related protein (AgRP) are potent food
      stimulating neuropeptides that are highly co-localised in arcuate nucleus neurons
      of the hypothalamus. Recent studies have shown that NPY and AgRP mRNA levels in
      these neurons respond similarly to fasting and leptin, indicating functional
      redundancy of the neuropeptide systems in these orexigenic neurons. However, we
      have found that NPY and AgRP mRNA expression in arcuate nucleus neurons are
      dissociated immediately following a stressful event. Two hours following a brief
      session of inescapable foot shocks, AgRP mRNA levels are down-regulated (P <
      0.0001). In contrast, NPY mRNA levels are up-regulated (P < 0.0001). To provide
      physiological relevance for this acute down-regulation of AgRP, an inverse
      agonist of melanocortin receptors, we have shown that acute
      intracerebroventricular injection of a melanocortin receptor agonist, alpha
      melanocyte-stimulating hormone (alpha-MSH), caused a significantly stronger
      activation of the hypothalamus-pituitary-adrenal-cortical (HPA) axis following a
      stressful event than in controls. Thus, AgRP and NPY mRNA levels in similar
      arcuate nucleus neurons are differentially regulated following a stressful event.
      This may contribute to increased sensitivity for alpha-MSH to activate the HPA
      axis following a repeated stressful experience.

PMID- 16087730
TI  - Suppressors of cytokine signaling proteins in human preterm placental tissues.
AB  - Decreased suppressors of cytokine signaling (SOCS) activity in human gestational
      tissues may play a part in the onset/progression of term labor. Since SOCS
      proteins negatively regulate cytokine-mediated inflammatory processes, we
      hypothesized that SOCS proteins are elevated in gestational tissues from
      spontaneous preterm deliveries with intrauterine infection. SOCS1, -2 and -3
      mRNAs and proteins were detectable by RT-PCR and immunoblotting respectively, in
      preterm amnion, choriodecidua and placenta, irrespective of infection status.
      Immunoperoxidase staining localized SOCS1, -2 and -3 to all cell types of the
      gestational membranes, with infiltrating leukocytes reacting strongly in infected
      tissues. In villous placenta, SOCS was immunolocalized to the syncytiotrophoblast
      with marked staining of round mesenchymal cells, possibly Hofbauer cells. Nuclear
      SOCS staining was seen in amnion, chorion and placental syncytiotrophoblasts.
      SOCS proteins were, in general, significantly more abundant in placenta compared
      with amnion or choriodecidua. Placental SOCS1 and interleukin-1beta
      concentrations were positively correlated (r(2)=0.47; P<0.05). However, no
      changes in SOCS levels in any tissues were observed with intrauterine infection.
      The relatively large amounts of SOCS proteins in the placenta may reflect a
      placenta-specific immunoprotective response to minimize the elaboration and
      effects of cytokines with potential to harm the placenta and fetus. Lack of labor
      associated changes in SOCS levels suggests that the regulation of SOCS expression
      in preterm gestational tissues differs from those at term, perhaps reflecting
      roles in regulating placental somatotropic responses.

PMID- 16087731
TI  - Internalization of gonadotropin-releasing hormone receptors (GnRHRs): does
      arrestin binding to the C-terminal tail target GnRHRs for dynamin-dependent
      internalization?
AB  - Activation of seven-transmembrane receptors is typically followed by
      desensitization and arrestin-dependent internalization via vesicles that are
      pinched off by a dynamin collar. Arrestins also scaffold Src, which mediates
      dynamin-dependent internalization of beta2-adrenergic receptors. Type I mammalian
      gonadotropin-releasing hormone receptors (GnRHRs) do not rapidly desensitize or
      internalize (characteristics attributed to their unique lack of C-terminal tails)
      whereas non-mammalian GnRHRs (that have C-terminal tails) are rapidly
      internalized and desensitized. Moreover, internalization of Xenopus (X) GnRHRs is
      dynamin-dependent whereas that of human (h) GnRHRs is not, raising the
      possibility that binding of arrestin to the C-terminal tails of GnRHRs targets
      them to the dynamin-dependent internalization pathway. To test this we have
      compared wild-type GnRHRs with chimeric receptors (XGnRHR C-terminal tail added
      to the hGnRHR alone (h.XtGnRHR) or with exchange of the third intracellular loops
      (h.Xl.XtGnRHR)). We show that adding the XGnRHR C-terminal tail facilitates
      arrestin- and dynamin-dependent internalization as well as arrestin/green
      fluorescent protein translocation, but Src (or mitogen-activated protein
      kinase/extracellular-signal-regulated kinase kinase) inhibition does not slow
      internalization, and h.XtGnRHR internalization is slower than that of the hGnRHR.
      Moreover, arrestin expression increased XGnRHR internalization even when dynamin
      was inhibited and h.Xl.XtGnRHR underwent rapid arrestin-dependent internalization
      without signaling to G(q/11). Thus, although the C-terminal tail can direct
      GnRHRs for arrestin- and dynamin-dependent internalization, this effect is not
      dependent on Src activation and arrestin can also facilitate dynamin-independent
      internalization.

PMID- 16087732
TI  - Estrogen-induced growth inhibition of human seminoma cells expressing estrogen
      receptor beta and aromatase.
AB  - It is now well established that estrogens participate in the control of normal
      spermatogenesis and endogenous or environmental estrogens are involved in
      pathological germ cell proliferation including testicular germ cell tumors.
      Studying a human testicular seminoma cell line, JKT-1, we show here that 17beta
      estradiol (10(-12) to 10(-6) M) induced in vitro a significant dose-dependent
      decrease of cell growth. This antiproliferative effect was maximum after 4 days
      of exposure at a physiologically intratesticular concentration of 10(-9) M, close
      to the K(d) of ER, and reversed by ICI 182780, an ER antagonist, suggesting an ER
      mediated pathway. By RT-PCR and Western blot we were able to confirm that JKT-1,
      like tumoral seminoma cells and normal human testicular basal germ cells,
      expresses estrogen receptor beta (ERbeta), including ERbeta1 and ERbeta2, a
      dominant negative variant, but not ERalpha. Using immunofluorescence and confocal
      microscopy, ERbeta was observed as perinuclear intracytoplasmic spots in JKT-1
      and tumoral seminoma cells without significant translocation of ERbeta into the
      nucleus, under 17beta-estradiol exposure. Double staining observed by confocal
      microscopy revealed that ERbeta colocalized in JKT-1 cells with cytochrome C, a
      mitochondrial marker. We report for the first time the expression of a functional
      aromatase complex in seminoma cells as assessed by RT-PCR, Western blot and
      enzymatic assay. Seminoma cells are able to respond to estrogens through a
      possible autocrine or paracrine loop. These preliminary results support estrogen
      dependency of human testicular seminoma, the most frequent tumor of young men,
      and suggest potential pharmacological use. Whether this estrogen control,
      however, involves an ERbeta-mediated stimulation of cell apoptosis and/or an
      ERbeta-mediated inhibition of cell proliferation, remains to be further
      determined.

PMID- 16087733
TI  - Multiplex PCR: use of heat-stable Thermus thermophilus RecA protein to minimize
      non-specific PCR products.
AB  - In this paper we report that the inclusion of heat-resistant RecA protein from a
      thermophilic bacteria, Thermus thermophilus, and its cofactor (ATP) in PCR
      effectively eliminates non-specific PCR products. The effect of RecA protein,
      which catalyzes pairing between homologous DNA molecules with great fidelity in
      genetic recombination, is due to its promotion of precise priming in PCR (i.e.
      priming at sites where the primer sequence is completely complementary to that of
      the target sequence). In addition, the RecA protein substantially reduces the
      primer concentration required for PCR. These experimental results have led to the
      realization of multiplex PCR, which involves PCR for multiple sites in the same
      reaction mixture. We were able to successfully perform multiplex PCR with over a
      dozen reactions without affecting the amplification pattern of the PCR products.

PMID- 16087734
TI  - Group 13 HOX proteins interact with the MH2 domain of R-Smads and modulate Smad
      transcriptional activation functions independent of HOX DNA-binding capability.
AB  - Interactions with co-factors provide a means by which HOX proteins exert
      specificity. To identify candidate protein interactors of HOXA13, we created and
      screened an E11.5-E12.5, distal limb bud yeast two-hybrid prey library. Among the
      interactors, we isolated the BMP-signaling effector Smad5, which interacted with
      the paralogous HOXD13 but not with HOXA11 or HOXA9, revealing unique interaction
      capabilities of the AbdB-like HOX proteins. Using deletion mutants, we determined
      that the MH2 domain of Smad5 is necessary for HOXA13 interaction. This is the
      first report demonstrating an interaction between HOX proteins and the MH2 domain
      of Smad proteins. HOXA13 and HOXD13 also bind to other BMP and TGF-beta/Activin
      regulated Smad proteins including Smad1 and Smad2, but not Smad4. Furthermore,
      HOXD13 could be co-immunoprecipitated with Smad1 from cells. Expression of
      HOXA13, HOXD13 or a HOXD13 homeodomain mutant (HOXD13(IQN>AAA)) antagonized TGF
      beta-stimulated transcriptional activation of the pAdtrack-3TP-Lux reporter
      vector in Mv1Lu cells as well as the Smad3/Smad4-activated pTRS6-E1b promoter in
      Hep3B cells. Finally, using mammalian one-hybrid assay, we show that
      transcriptional activation by a GAL4/Smad3-C-terminus fusion protein is
      specifically inhibited by HOXA13. Our results identify a new co-factor for HOX
      group 13 proteins and suggest that HOX proteins may modulate Smad-mediated
      transcriptional activity through protein-protein interactions without the
      requirement for HOX monomeric DNA-binding capability.

PMID- 16087735
TI  - Identification and analysis of ribonuclease P and MRP RNA in a broad range of
      eukaryotes.
AB  - RNases P and MRP are ribonucleoprotein complexes involved in tRNA and rRNA
      processing, respectively. The RNA subunits of these two enzymes are structurally
      related to each other and play an essential role in the enzymatic reaction. Both
      of the RNAs have a highly conserved helical region, P4, which is important in the
      catalytic reaction. We have used a bioinformatics approach based on conserved
      elements to computationally analyze available genomic sequences of eukaryotic
      organisms and have identified a large number of novel nuclear RNase P and MRP RNA
      genes. For MRP RNA for instance, this investigation increases the number of known
      sequences by a factor of three. We present secondary structure models of many of
      the predicted RNAs. Although all sequences are able to fold into the consensus
      secondary structure of P and MRP RNAs, a striking variation in size is observed,
      ranging from a Nosema locustae MRP RNA of 160 nt to much larger RNAs, e.g. a
      Plasmodium knowlesi P RNA of 696 nt. The P and MRP RNA genes appear in tandem in
      some protists, further emphasizing the close evolutionary relationship of these
      RNAs.

PMID- 16087736
TI  - Refinement of docked protein-ligand and protein-DNA structures using low
      frequency normal mode amplitude optimization.
AB  - Prediction of structural changes resulting from complex formation, both in
      ligands and receptors, is an important and unsolved problem in structural
      biology. In this work, we use all-atom normal modes calculated with the Elastic
      Network Model as a basis set to model structural flexibility during formation of
      macromolecular complexes and refine the non-bonded intermolecular energy between
      the two partners (protein-ligand or protein-DNA) along 5-10 of the lowest
      frequency normal mode directions. The method handles motions unrelated to the
      docking transparently by first applying the modes that improve non-bonded energy
      most and optionally restraining amplitudes; in addition, the method can correct
      small errors in the ligand position when the first six rigid-body modes are
      switched on. For a test set of six protein receptors that show an open-to-close
      transition when binding small ligands, our refinement scheme reduces the protein
      coordinate cRMS by 0.3-3.2 A. For two test cases of DNA structures interacting
      with proteins, the program correctly refines the docked B-DNA starting form into
      the expected bent DNA, reducing the DNA cRMS from 8.4 to 4.8 A and from 8.7 to
      5.4 A, respectively. A public web server implementation of the refinement method
      is available at http://lorentz.immstr.pasteur.fr.

PMID- 16087737
TI  - Mating type loci of Sporisorium reilianum: novel pattern with three a and
      multiple b specificities.
AB  - Sporisorium reilianum and Ustilago maydis are two closely related smut fungi,
      which both infect maize but differ fundamentally in their mode of plant invasion
      and site of symptom development. As a prelude to studying the molecular basis of
      these differences, we have characterized the mating type loci of S. reilianum. S.
      reilianum has two unlinked mating type loci, a and b. Genes in both loci and
      adjacent regions show a high degree of synteny to the corresponding genes of U.
      maydis. The b locus occurs in at least five alleles and encodes two subunits of a
      heterodimeric homeodomain transcription factor, while the a locus encodes a
      pheromone/receptor system. However, in contrast to that of U. maydis, the a locus
      of S. reilianum exists in three alleles containing two active pheromone genes
      each. The alleles of the a locus appear to have arisen through recent
      recombination events within the locus itself. This has created a situation where
      each pheromone is specific for recognition by only one mating partner.

PMID- 16087738
TI  - Tetracycline-inducible gene expression and gene deletion in Candida albicans.
AB  - The genetic analysis of Candida albicans, the major fungal pathogen of humans, is
      hampered by its diploid genome, the absence of a normal sexual cycle, and a
      nonstandard codon usage. Although effective methods to study gene function have
      been developed in the past years, systems to control gene expression in C.
      albicans are limited. We have established a system that allows induction of gene
      expression in C. albicans by the addition of tetracycline (Tet). By fusing
      genetically modified versions of the reverse Tet repressor from Escherichia coli
      and the transcription activation domain of the Gal4 protein from Saccharomyces
      cerevisiae, a C. albicans-adapted reverse Tet-dependent transactivator (rtTA) was
      created that was expressed from the constitutive ADH1 or the opaque-specific OP4
      promoter. To monitor Tet-inducible gene expression, the caGFP reporter gene was
      placed under the control of a Tet-dependent promoter, obtained by fusing a
      minimal promoter from C. albicans to seven copies of the Tet operator sequence.
      Fluorescence of the cells demonstrated that gene expression could be efficiently
      induced by the addition of doxycycline in yeast, hyphal, and opaque cells of C.
      albicans. The Tet-inducible gene expression system was then used to manipulate
      the behavior of the various growth forms of C. albicans. Tet-induced expression
      of a dominant-negative CDC42 allele resulted in growth arrest as large,
      multinucleate cells. Filamentous growth was efficiently inhibited under all
      tested hyphal-growth-promoting conditions by Tet-inducible expression of the NRG1
      repressor. Tet-induced expression of the MTLa1 gene in opaque cells of an
      MTLalpha strain forced the cells to switch to the white phase, whereas Tet
      induced expression of the MTLa2 transcription factor induced shmooing. When the
      ecaFLP gene, encoding the site-specific recombinase FLP, was placed under the
      control of the Tet-dependent promoter, Tet-inducible deletion of genes which were
      flanked by the FLP target sequences was achieved with high efficiency to generate
      conditional null mutants. In combination with the dominant selection marker
      caSAT1, the Tet-inducible gene expression system was also applied in C. albicans
      wild-type strains, including drug-resistant clinical isolates that overexpressed
      the MDR1, CDR1, and CDR2 multidrug efflux pumps. This system, therefore, allows a
      growth medium-independent, Tet-inducible expression and deletion of genes in C.
      albicans and provides a convenient, versatile new tool to study gene function and
      manipulate cellular behavior in this model pathogenic fungus.

PMID- 16087739
TI  - Genomewide identification of Sko1 target promoters reveals a regulatory network
      that operates in response to osmotic stress in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, the ATF/CREB transcription factor Sko1 (Acr1)
      regulates the expression of genes induced by osmotic stress under the control of
      the high osmolarity glycerol (HOG) mitogen-activated protein kinase pathway. By
      combining chromatin immunoprecipitation and microarrays containing essentially
      all intergenic regions, we estimate that yeast cells contain approximately 40
      Sko1 target promoters in vivo; 20 Sko1 target promoters were validated by direct
      analysis of individual loci. The ATF/CREB consensus sequence is not statistically
      overrepresented in confirmed Sko1 target promoters, although some sites are
      evolutionarily conserved among related yeast species, suggesting that they are
      functionally important in vivo. These observations suggest that Sko1 association
      in vivo is affected by factors beyond the protein-DNA interaction defined in
      vitro. Sko1 binds a number of promoters for genes directly involved in defense
      functions that relieve osmotic stress. In addition, Sko1 binds to the promoters
      of genes encoding transcription factors, including Msn2, Mot3, Rox1, Mga1, and
      Gat2. Stress-induced expression of MSN2, MOT3, and MGA1 is diminished in sko1
      mutant cells, while transcriptional regulation of ROX1 seems to be unaffected.
      Lastly, Sko1 targets PTP3, which encodes a phosphatase that negatively regulates
      Hog1 kinase activity, and Sko1 is required for osmotic induction of PTP3
      expression. Taken together our results suggest that Sko1 operates a
      transcriptional network upon osmotic stress, which involves other specific
      transcription factors and a phosphatase that regulates the key component of the
      signal transduction pathway.

PMID- 16087740
TI  - Polarized morphogenesis regulator Spa2 is required for the function of putative
      stretch-activated Ca2+-permeable channel component Mid1 in Saccharomyces
      cerevisiae.
AB  - Mid1 is a putative stretch-activated Ca2+ channel component and is required for
      the maintenance of viability in the mating process. In response to mating
      pheromone, the mid1 mutant normally forms a pointed mating projection but
      eventually dies. This phenotype is called the mid phenotype. To identify a
      protein regulating Mid1 or regulated by Mid1, we isolated a multicopy suppressor
      that rescues the mid1-1 mutant from mating pheromone-induced death and found that
      it encodes a truncated Spa2 protein lacking an amino-terminal region responsible
      for interaction with components of the mitogen-activated protein kinase cascades.
      One of these SPA2 alleles was SPA2DeltaN, whose product lacked the region from
      Ser5 to Leu230. SPA2DeltaN on a multicopy plasmid (YEpSPA2DeltaN) complemented
      the mid phenotype but not another phenotype, low Ca2+ accumulation, of the mid1-1
      mutant. Neither SPA2DeltaN on a low-copy plasmid nor wild-type SPA2 on a
      multicopy plasmid had suppressive activity. The SPA2 gene is involved in the
      formation of a pointed mating projection, and cells of the spa2Delta mutant
      lacking Spa2 are viable and develop a peanut shell-like structure when exposed to
      mating pheromone. Like the spa2Delta mutant, the mid1-1 spa2Delta double mutant
      and the mid1-1/YEpSPA2DeltaN strain developed the peanut shell-like structure.
      The mid1-1 spa2Delta double mutant did not have the mid phenotype, indicating
      that SPA2 is epistatic to MID1. Overexpression of Spa2DeltaN abolished the
      localization of Spa2-green fluorescent protein to the tip of the mating
      projection. These results suggest that the Spa2DeltaN protein interferes with the
      localization of the normal Spa2 protein and thereby prevents cells from entering
      the mating process. Therefore, we suggest that Mid1 function is influenced by
      Spa2 function through polarized morphogenesis.

PMID- 16087741
TI  - Yapsins are a family of aspartyl proteases required for cell wall integrity in
      Saccharomyces cerevisiae.
AB  - The yeast cell wall is a crucial extracellular organelle that protects the cell
      from lysis during environmental stress and morphogenesis. Here, we demonstrate
      that the yapsin family of five glycosylphosphatidylinositol-linked aspartyl
      proteases is required for cell wall integrity in Saccharomyces cerevisiae. Yapsin
      null mutants show hypersensitivity to cell wall perturbation, and both the
      yps1Delta2Delta mutant and the quintuple yapsin mutant (5ypsDelta) undergo
      osmoremedial cell lysis at 37 degrees C. The cell walls of both 5ypsDelta and
      yps1Delta2Delta mutants have decreased amounts of 1,3- and 1,6-beta-glucan.
      Although there is decreased incorporation of both 1,3- and 1,6-beta-glucan in the
      5ypsDelta mutant in vivo, in vitro specific activity of both 1,3- and 1,6-beta
      glucan synthesis is similar to wild type, indicating that the yapsins affect
      processes downstream of glucan synthesis and that the yapsins may be involved in
      the incorporation or retention of cell wall glucan. Presumably as a response to
      the significant alterations in cell wall composition, the cell wall integrity
      mitogen-activated kinase signaling cascade (PKC1-MPK pathway) is basally active
      in 5ypsDelta. YPS1 expression is induced during cell wall stress and remodeling
      in a PKC1-MPK1-dependent manner, indicating that Yps1p is a direct, and
      important, output of the cell wall integrity response. The Candida albicans
      (SAP9) and Candida glabrata (CgYPS1) homologues of YPS1 complement the phenotypes
      of the yps1Delta mutant. Taken together, these data indicate that the yapsins
      play an important role in glucan homeostasis in S. cerevisiae and that yapsin
      homologues may play a similar role in the pathogenic yeasts C. albicans and C.
      glabrata.

PMID- 16087742
TI  - The Rgd1p Rho GTPase-activating protein and the Mid2p cell wall sensor are
      required at low pH for protein kinase C pathway activation and cell survival in
      Saccharomyces cerevisiae.
AB  - The protein kinase C (PKC) pathway is involved in the maintenance of cell shape
      and cell integrity in Saccharomyces cerevisiae. Here, we show that this pathway
      mediates tolerance to low pH and that the Bck1 and Slt2 proteins belonging to the
      mitogen-activated protein kinase cascade are essential for cell survival at low
      pH. The PKC pathway is activated during acidification of the extracellular
      environment, and this activation depends mainly on the Mid2p cell wall sensor.
      Rgd1p, which encodes a Rho GTPase-activating protein for the small G proteins
      Rho3p and Rho4p, also plays a role in low-pH response. The rgd1Delta strain is
      sensitive to low pH, and Rgd1p activates the PKC pathway in an acidic
      environment. Inactivation of both genes in the double mutant rgd1Delta mid2Delta
      strain renders yeast cells unable to survive at low pH as in bck1Delta and
      slt2Delta strains. Our data provide evidence for the existence of two distinct
      ways, one involving Mid2p and the other involving Rgd1p, with both converging to
      the cell integrity pathway to mediate low-pH tolerance in Saccharomyces
      cerevisiae. Nevertheless, even if Rgd1p acts on the PKC pathway, it seems that
      its mediating action on low-pH tolerance is not limited to this pathway. As the
      Mid2p amount plays a role in rgd1Delta sensitivity to low pH, Mid2p seems to act
      more like a molecular rheostat, controlling the level of PKC pathway activity and
      thus allowing phenotypical expression of RGD1 inactivation.

PMID- 16087743
TI  - Disruption of histone deacetylase gene RPD3 accelerates PHO5 activation kinetics
      through inappropriate Pho84p recycling.
AB  - The histone deacetylase Rpd3p functions as a transcriptional repressor of a
      diverse set of genes, including PHO5. Here we describe a novel role for RPD3 in
      the regulation of phosphate transporter Pho84p retention in the cytoplasmic
      membrane. We show that under repressing conditions (with P(i)), PHO5 expression
      is increased in a pho4Delta rpd3Delta strain, demonstrating PHO regulatory
      pathway independence. However, the effect of RPD3 disruption on PHO5 activation
      kinetics is dependent on the PHO regulatory pathway. Upon switching to activating
      conditions (without P(i)), PHO5 transcripts accumulated more rapidly in rpd3Delta
      cells. This more rapid response correlates with a defect in phosphate uptake due
      to premature recycling of Pho84p, the high-affinity H+/PO4(3-) symporter. Thus,
      RPD3 also participates in PHO5 regulation through a previously unidentified
      effect on maintenance of high-affinity phosphate uptake during phosphate
      starvation. We propose that Rpd3p has a negative role in the regulation of Pho84p
      endocytosis.

PMID- 16087744
TI  - Distinct signaling pathways respond to arsenite and reactive oxygen species in
      Schizosaccharomyces pombe.
AB  - Exposure to certain metal and metalloid species, such as arsenic, cadmium,
      chromium, and nickel, has been associated with an increased risk of cancer in
      humans. The biological effects of these metals are thought to result from
      induction of reactive oxygen species (ROS) and inhibition of DNA repair enzymes,
      although alterations in signal transduction pathways may also be involved in
      tumor development. To better understand metal toxicity and its connection to ROS,
      we have compared the effects of arsenite and hydrogen peroxide in wild-type and
      mutant strains of the fission yeast Schizosaccharomyces pombe. An atf1Delta
      pap1Delta strain, which is defective in two transcription factors that control
      stress responses, is extremely sensitive to hydrogen peroxide but not to
      arsenite. A strain that lacks the transcription factor Zip1 has the opposite
      relationship. Spc1 (Sty1) mitogen-activated protein kinase (MAPK), a homologue of
      mammalian p38 MAPK, and the upstream MAPK kinase (MAPKK) Wis1 are essential for
      survival of both arsenite and hydrogen peroxide. Inactivation of two MAPKK
      kinases, Win1 and Wis4, almost completely eliminates Spc1 activation by arsenite,
      yet these cells survive arsenite treatment. The two-component phosphorelay
      protein Mcs4, which acts upstream of Win1 and Wis4 and is required for Spc1
      activation in response to oxidative stress, is not required for Spc1 activation
      in response to arsenite. We conclude that the toxic effects of arsenic are not
      strongly connected to oxidative stress and that although Spc1 is activated by
      arsenic exposure, the basal activity of Spc1 is largely sufficient for the
      survival of arsenic.

PMID- 16087745
TI  - Clonality and recombination in genetically differentiated subgroups of
      Cryptococcus gattii.
AB  - Cryptococcus gattii is a pathogenic yeast that together with Cryptococcus
      neoformans causes cryptococcosis in humans and animals. High numbers of viable C.
      gattii propagules can be obtained from certain species of Australian Eucalyptus
      camaldulensis trees, and an epidemiological link between Eucalyptus colonization
      and human exposure has been proposed. However, the highest prevalence of C.
      gattii cryptococcosis occurs in Papua New Guinea and in regions of Australia
      where the eucalypt species implicated to date are not endemic. This study
      investigated the population structure of three geographically distinct clinical
      and veterinary populations of C. gattii from Australia and Papua New Guinea. All
      populations that consisted of a genotype found frequently in Australia (VGI) were
      strongly clonal and were highly differentiated from one another. Two populations
      of the less common VGII genotype from Sydney and the Northern Territory had
      population structures inferring recombination. In addition, there was some
      evidence of reduced genetic differentiation between these geographically remote
      regions. In a companion study presented in this issue, VGII isolates were
      overwhelmingly more fertile than those of the VGI genotype, giving biological
      support to the indirect assessment of sexual exchange. It appears that the VGI
      genotype propagates clonally on eucalypts in Australia and on an unknown
      substrate in Papua New Guinea, with infection initiated by an unidentified
      infectious propagule. VGII isolates are completing their life cycles and may be
      dispersed via sexually produced basidiospores, which are also likely to initiate
      respiratory infection.

PMID- 16087746
TI  - Clinical and environmental isolates of Cryptococcus gattii from Australia that
      retain sexual fecundity.
AB  - Cryptococcus gattii is a primary pathogenic yeast that causes disease in both
      animals and humans. It is closely related to Cryptococcus neoformans and diverged
      from a common ancestor approximately 40 million years ago. While C. gattii has a
      characterized sexual cycle dependent upon a dimorphic region of the genome known
      as the MAT locus, mating has rarely been observed in this species. In this study,
      we identify for the first time clinical (both human and veterinary) and
      environmental isolates from Australia that retain sexual fecundity. A collection
      of 120 isolates from a variety of geographic locations was analyzed for molecular
      type, mating type, and the ability to develop mating structures when cocultured
      with fertile tester strains. Nine isolates produced dikaryotic filaments with
      paired nuclei, fused clamp connections, and basidiospores. DNA sequence analysis
      of three genes (URA5, the MATalpha-specific SXI1alpha gene, and the MATa-specific
      SXI2a gene) revealed little or no variability in URA5 and SXI2a, respectively.
      However across the 108 MATalpha strains sequenced, the SXI1alpha gene was found
      to exist as 11 different alleles. Phylogenetic analysis found most variation to
      occur in the more fertile genotypes. Although some lineages of Australian C.
      gattii have retained the ability to mate, the majority of isolates were sterile,
      suggesting that asexuality is the dominant mode of propagation in these
      populations.

PMID- 16087747
TI  - Cryptococcus neoformans gene expression during murine macrophage infection.
AB  - The fungal pathogen Cryptococcus neoformans survives phagocytosis by macrophages
      and proliferates within, ultimately establishing latent infection as a
      facultative intracellular pathogen that can escape macrophage control to cause
      disseminated disease. This process is hypothesized to be important for C.
      neoformans pathogenesis; however, it is poorly understood how C. neoformans
      adapts to and overcomes the hostile intracellular environment of the macrophage.
      Using DNA microarray technology, we have investigated the transcriptional
      response of C. neoformans to phagocytosis by murine macrophages. The expression
      profiles of several genes were verified using quantitative reverse transcription
      PCR and a green fluorescent protein reporter strain. Multiple membrane
      transporters for hexoses, amino acids, and iron were up-regulated, as well as
      genes involved in responses to oxidative stress. Genes involved in autophagy,
      peroxisome function, and lipid metabolism were also induced. Interestingly,
      almost the entire mating type locus displayed increased expression 24 h after
      internalization, suggesting an intrinsic connection between infection and the MAT
      locus. Genes in the Gpa1-cyclic AMP-protein kinase A pathway were also up
      regulated. Both gpa1 and pka1 mutants were found to be compromised in macrophage
      infection, confirming the important role of this virulence pathway. A large
      proportion of the repressed genes are involved in ribosome-related functions,
      rRNA processing, and translation initiation/elongation, implicating a reduction
      in translation as a central response to phagocytosis. In summary, this gene
      expression profile allows us to interpret the adaptation of C. neoformans to the
      intracellular infection process and informs the search for genes encoding novel
      virulence attributes.

PMID- 16087748
TI  - Phenotypic switching in Candida glabrata accompanied by changes in expression of
      genes with deduced functions in copper detoxification and stress.
AB  - Most strains of Candida glabrata switch spontaneously between a number of
      phenotypes distinguishable by graded brown coloration on agar containing 1 mM
      CuSO4, a phenomenon referred to as "core switching." C. glabrata also switches
      spontaneously and reversibly from core phenotypes to an irregular wrinkle (IWr)
      phenotype, a phenomenon referred to as "irregular wrinkle switching." To identify
      genes differentially expressed in the core phenotypes white (Wh) and dark brown
      (DB), a cDNA subtraction strategy was employed. Twenty-three genes were
      identified as up-regulated in DB, four in Wh, and six in IWr. Up-regulation was
      verified in two unrelated strains, one a and one alpha strain. The functions of
      these genes were deduced from the functions of their Saccharomyces cerevisiae
      orthologs. The majority of genes up-regulated in DB (78%) played deduced roles in
      copper assimilation, sulfur assimilation, and stress responses. These genes were
      differentially up-regulated in DB even though the conditions of growth for Wh and
      DB, including CuSO4 concentration, were identical. Hence, the regulation of these
      genes, normally regulated by environmental cues, has been usurped by switching,
      presumably as an adaptation to the challenging host environment. These results
      are consistent with the suggestion that switching provides colonizing populations
      with a minority of cells expressing a phenotype that allows them to enrich in
      response to an environmental challenge, a form of rapid adaptation. However, DB
      is the most commonly expressed phenotype at sites of host colonization, in the
      apparent absence of elevated copper levels. Hence, up-regulation of these genes
      by switching suggests that in some cases they may play roles in colonization and
      virulence not immediately obvious from the roles played by their orthologs in S.
      cerevisiae.

PMID- 16087749
TI  - Histone H3 K36 methylation is associated with transcription elongation in
      Schizosaccharomyces pombe.
AB  - Set2 methylation of histone H3 at lysine 36 (K36) has recently been shown to be
      associated with RNA polymerase II (Pol II) elongation in Saccharomyces
      cerevisiae. However, whether this modification is conserved and associated with
      transcription elongation in other organisms is not known. Here we report the
      identification and characterization of the Set2 ortholog responsible for K36
      methylation in the fission yeast Schizosaccharomyces pombe. We find that similar
      to the budding yeast enzyme, S. pombe Set2 is also a robust nucleosome-selective
      H3 methyltransferase that is specific for K36. Deletion of the S. pombe set2+
      gene results in complete abolishment of K36 methylation as well as a slow-growth
      phenotype on plates containing synthetic medium. These results indicate that Set2
      is the sole enzyme responsible for this modification in fission yeast and is
      important for cell growth under stressed conditions. Using the chromatin
      immunoprecipitation assay, we demonstrate that K36 methylation in S. pombe is
      associated with the transcribed regions of Pol II-regulated genes and is devoid
      in regions that are not transcribed by Pol II. Consistent with a role for Set2 in
      transcription elongation, we find that S. pombe Set2 associates with the
      hyperphosphorylated form of Pol II and can fully rescue K36 methylation and Pol
      II interaction in budding yeast cells deleted for Set2. These results, along with
      our finding that K36 methylation is highly conserved among eukaryotes, imply a
      conserved role for this modification in the transcription elongation process.

PMID- 16087750
TI  - Methylation of histone H3 lysine 36 is required for normal development in
      Neurospora crassa.
AB  - The SET domain is an evolutionarily conserved domain found predominantly in
      histone methyltransferases (HMTs). The Neurospora crassa genome includes nine SET
      domain genes (set-1 through set-9) in addition to dim-5, which encodes a histone
      H3 lysine 9 HMT required for DNA methylation. We demonstrate that Neurospora set
      2 encodes a histone H3 lysine 36 (K36) methyltransferase and that it is essential
      for normal growth and development. We used repeat induced point mutation to make
      a set-2 mutant (set-2(RIP1)) with multiple nonsense mutations. Western analyses
      revealed that the mutant lacks SET-2 protein and K36 methylation. An amino
      terminal fragment that includes the AWS, SET, and post-SET domains of SET-2
      proved sufficient for K36 HMT activity in vitro. Nucleosomes were better
      substrates than free histones. The set-2(RIP1) mutant grows slowly, conidiates
      poorly, and is female sterile. Introducing the wild-type gene into the mutant
      complemented the defects, confirming that they resulted from loss of set-2
      function. We replaced the wild-type histone H3 gene (hH3) with an allele
      producing a Lys to Leu substitution at position 36 and found that this hH3(K36L)
      mutant phenocopied the set-2(RIP1) mutant, confirming that the observed defects
      in growth and development result from inability to methylate K36 of H3. Finally,
      we used chromatin immunoprecipitation to demonstrate that actively transcribed
      genes in Neurospora crassa are enriched for H3 methylated at lysines 4 and 36.
      Taken together, our results suggest that methylation of K36 in Neurospora crassa
      is essential for normal growth and development.

PMID- 16087751
TI  - The pkaB gene encoding the secondary protein kinase A catalytic subunit has a
      synthetic lethal interaction with pkaA and plays overlapping and opposite roles
      in Aspergillus nidulans.
AB  - Filamentous fungal genomes contain two distantly related cyclic AMP-dependent
      protein kinase A catalytic subunits (PKAs), but only one PKA is found to play a
      principal role. In Aspergillus nidulans, PkaA is the primary PKA that positively
      functions in vegetative growth and spore germination but negatively controls
      asexual sporulation and production of the mycotoxin sterigmatocystin. In this
      report, we present the identification and characterization of pkaB, encoding the
      secondary PKA in A. nidulans. Although deletion of pkaB alone does not cause any
      apparent phenotypic changes, the absence of both pkaB and pkaA is lethal,
      indicating that PkaB and PkaA are essential for viability of A. nidulans.
      Overexpression of pkaB enhances hyphal proliferation and rescues the growth
      defects caused by DeltapkaA, indicating that PkaB plays a role in vegetative
      growth signaling. However, unlike DeltapkaA, deletion of pkaB does not suppress
      the fluffy-autolytic phenotype resulting from DeltaflbA. While upregulation of
      pkaB rescues the defects of spore germination resulting from DeltapkaA in the
      presence of glucose, overexpression of pkaB delays spore germination.
      Furthermore, upregulation of pkaB completely abolishes spore germination on
      medium lacking a carbon source. In addition, upregulation of pkaB enhances the
      level of submerged sporulation caused by DeltapkaA and reduces hyphal tolerance
      to oxidative stress. In conclusion, PkaB is the secondary PKA that has a
      synthetic lethal interaction with PkaA, and it plays an overlapping role in
      vegetative growth and spore germination in the presence of glucose but an
      opposite role in regulating asexual sporulation, germination in the absence of a
      carbon source, and oxidative stress responses in A. nidulans.

PMID- 16087752
TI  - Transcriptional switch of the dia1 and impA promoter during the
      growth/differentiation transition.
AB  - When growth stops due to the depletion of nutrients, Dictyostelium cells rapidly
      turn off vegetative genes and start to express developmental genes. One of the
      early developmental genes, dia1, is adjacent to a vegetative gene, impA, on
      chromosome 4. An intergenic region of 654 bp separates the coding regions of
      these divergently transcribed genes. Constructs carrying the intergenic region
      expressed a reporter gene (green fluorescent protein gene) that replaced impA in
      growing cells and a reporter gene that replaced dia1 (DsRed) during development.
      Deletion of a 112-bp region proximal to the transcriptional start site of impA
      resulted in complete lack of expression of both reporter genes during growth or
      development. At the other end of the intergenic region there are two copies of a
      motif that is also found in the carA regulatory region. Removing one copy of this
      repeat reduced impA expression twofold. Removing the second copy had no further
      consequences. Removing the central portion of the intergenic region resulted in
      high levels of expression of dia1 in growing cells, indicating that this region
      contains a sequence involved in repression during the vegetative stage. Gel shift
      experiments showed that a nuclear protein present in growing cells recognizes the
      sequence GAAGTTCTAATTGATTGAAG found in this region. This DNA binding activity is
      lost within the first 4 h of development. Different nuclear proteins were found
      to recognize the repeated sequence proximal to dia1. One of these became
      prevalent after 4 h of development. Together these regulatory components at least
      partially account for this aspect of the growth-to-differentiation transition.

PMID- 16087756
TI  - Chaperoning motor neurons.

PMID- 16087753
TI  - Ubiquinone synthesis in mitochondrial and microsomal subcellular fractions of
      Pneumocystis spp.: differential sensitivities to atovaquone.
AB  - The lung pathogen Pneumocystis spp. is the causative agent of a type of pneumonia
      that can be fatal in people with defective immune systems, such as AIDS patients.
      Atovaquone, an analog of ubiquinone (coenzyme Q [CoQ]), inhibits mitochondrial
      electron transport and is effective in clearing mild to moderate cases of the
      infection. Purified rat-derived intact Pneumocystis carinii cells synthesize de
      novo four CoQ homologs, CoQ7, CoQ8, CoQ9, and CoQ10, as demonstrated by the
      incorporation of radiolabeled precursors of both the benzoquinone ring and the
      polyprenyl chain. A central step in CoQ biosynthesis is the condensation of p
      hydroxybenzoic acid (PHBA) with a long-chain polyprenyl diphosphate molecule. In
      the present study, CoQ biosynthesis was evaluated by the incorporation of PHBA
      into completed CoQ molecules using P. carinii cell-free preparations. CoQ
      synthesis in whole-cell homogenates was not affected by the respiratory
      inhibitors antimycin A and dicyclohexylcarbodiimide but was diminished by
      atovaquone. Thus, atovaquone has inhibitory activity on both electron transport
      and CoQ synthesis in this pathogen. Furthermore, both the mitochondrial and
      microsomal fractions were shown to synthesize de novo all four P. carinii CoQ
      homologs. Interestingly, atovaquone inhibited microsomal CoQ synthesis, whereas
      it had no effect on mitochondrial CoQ synthesis. This is the first pathogenic
      eukaryotic microorganism in which biosynthesis of CoQ molecules from the initial
      PHBA:polyprenyl transferase reaction has been unambiguously shown to occur in two
      distinct compartments of the same cell.

PMID- 16087754
TI  - Candida albicans biofilm-defective mutants.
AB  - Biofilm formation plays a key role in the life cycles and subsistence of many
      microorganisms. For the human fungal pathogen Candida albicans, biofilm
      development is arguably a virulence trait, because medical implants that serve as
      biofilm substrates are significant risk factors for infection. The development of
      C. albicans biofilms in vitro proceeds through an early phase, in which yeast
      cells populate a substrate, an intermediate phase, in which pseudohyphal and
      hyphal cell types are produced, and a maturation phase, in which continued cell
      growth is accompanied by accumulation of an extracellular matrix. Here we report
      the results of a screen for C. albicans biofilm-defective mutants, in which
      homozygous insertions in NUP85, MDS3, KEM1, and SUV3 were found to block biofilm
      development. Confocal microscopic examination suggests that nup85, suv3, and mds3
      mutations cause early-phase arrest, whereas the kem1 mutation causes intermediate
      phase arrest. All of the mutants are defective in hypha production in several
      media. Analysis of mixed-biofilm development indicates that all of the mutants
      are defective in the production of hyphae in the context of a biofilm. Because
      all of the mutants are defective in the retention of cells in the biofilm, we
      infer that hyphae provide an adherent scaffold that stabilizes the biofilm
      structure.

PMID- 16087757
TI  - Supportive care for patients with Guillain-Barre syndrome.
AB  - A multidisciplinary consensus group searched MEDLINE from 1966 to May 2003,
      extracted relevant references, and prepared recommendations on supportive care
      for Guillain-Barre syndrome. In the absence of randomized controlled trials, we
      agreed on recommendations by consensus based on observational studies and expert
      opinion. In the acute phase in bed-bound adult patients, the group recommended
      the use of heparin and graduated pressure stockings to prevent deep vein
      thrombosis, monitoring for blood pressure, pulse, autonomic disturbances, and
      respiratory failure, and the timely institution of artificial ventilation and
      tracheostomy. Pain management is difficult, but carbamazepine or gabapentin may
      help. The cautious use of narcotic analgesics may be needed. Disabled patients
      should be treated by a multidisciplinary rehabilitation team and should receive
      an assistive exercise program. Persistent fatigue following Guillain-Barre
      syndrome is common and may be helped by an exercise program. Because of a very
      small and possibly only theoretical increase in the risk of recurrence following
      immunization, the need for immunization should be reviewed on an individual
      basis. More research is needed to identify optimal methods for all aspects of
      supportive care.

PMID- 16087758
TI  - Mutation analysis of the small heat shock protein 27 gene in chinese patients
      with Charcot-Marie-Tooth disease.
AB  - BACKGROUND: Charcot-Marie-Tooth (CMT) disease, the most common hereditary
      peripheral neuropathy, is highly clinically and genetically heterogeneous, and
      mutations in at least 18 genes have been identified. Recently, mutations in small
      heat shock protein 27 (Hsp27) were reported to cause CMT disease type 2F and
      distal hereditary motor neuropathy. OBJECTIVE: To investigate the frequency and
      phenotypic features of an Hsp27 mutation in Chinese patients with CMT disease.
      DESIGN: DNA samples from 114 unrelated patients with CMT disease were screened
      for mutations in Hsp27 by polymerase chain reaction and direct sequencing. A
      cosegregated study was performed using the MbiI restriction endonuclease, and 50
      healthy control subjects were analyzed. Haplotype analysis was performed using 5
      short tandem repeat markers to analyze whether the families with the same
      mutation probably had a common ancestor. RESULTS: One missense mutation, C379T,
      was detected in 4 autosomal dominant families with CMT disease type 2, and
      haplotype analysis indicated that the 4 families probably had a common founder.
      The frequency of the Hsp27 mutation is 0.9% (1/111) in Chinese patients with CMT
      disease in our study, and the phenotypes were characterized by later onset (age,
      35-60 years) and mild sensory impairments. Electrophysiological findings showed
      moderately to severely slowed nerve conduction velocities in lower limb nerves
      but normal or mildly reduced velocities in upper limb nerves. CONCLUSIONS: To our
      knowledge, this is the first report of an Hsp27 mutation in the People's Republic
      of China. The C379T mutation in Hsp27 also causes CMT disease type 2, except for
      distal hereditary motor neuropathy, and the phenotypes are distinct from the
      family with CMT disease type 2F described previously. A mutation of Hsp27 may be
      uncommon in Chinese patients with CMT disease.

PMID- 16087759
TI  - Impaired clearance of microemboli and cerebrovascular symptoms during carotid
      stenting procedures.
AB  - BACKGROUND: Transcranial Doppler monitoring shows a high prevalence of
      microemboli during carotid artery stenting (CAS); however, the occurrence of
      cerebrovascular symptoms (CVSs) does not seem to be related to the microembolic
      load. OBJECTIVE: To evaluate embolic and hemodynamic transcranial Doppler
      monitoring findings and their relationships with the occurrence of procedural
      CVSs. Patients Fifty-four patients who had carotid stenosis of more than 70%
      underwent a total of 57 CAS procedures during transcranial Doppler monitoring of
      mean blood flow velocity and microembolic signals in the middle cerebral artery.
      The occurrence of transient ischemic attack, transient monocular blindness, and
      stroke during the CAS procedure was considered CVSs. RESULTS: Nine (15.8%) of the
      57 patients had CVSs during the procedure (ie, 6 patients with transient ischemic
      attack, 1 with transient monocular blindness, 1 with a minor stroke, and 1 with a
      major stroke). The mean blood flow velocity median values were statistically
      significantly lower (P < .001) in the group of 9 patients with CVSs (36 cm/s;
      interquartile range, 32.3-38.5) compared with the 48 without CVSs (48 cm/s;
      interquartile range, 41.5-52). The median number of isolated microembolic signals
      was similar in the 2 groups (72; interquartile range, 66-81 vs 75; interquartile
      range, 67-83.5). The median number of microembolic signal showers (clusters of
      too many signals to be counted separately in one cardiac cycle) presented a
      nonsignificant prevalence in the patients with CVSs (9; interquartile range, 7.5
      11.2) compared with the ones without CVSs (8.2; interquartile range, 7-9).
      CONCLUSION: The low flow velocity in the middle cerebral artery may impair the
      clearance of the microembolic load and should be considered a precursor of CVSs
      during the CAS procedure.

PMID- 16087760
TI  - The syndrome of combined polar and paramedian thalamic infarction.
AB  - BACKGROUND: Occlusion of the polar or the paramedian arteries of the thalamus
      usually leads to distinct infarcts with specific clinical and imaging correlates.
      However, vascular variation is such that in up to one third of humans, the polar
      artery is missing and its territory taken over by the paramedian arteries.
      OBJECTIVE: To provide attention to the corresponding stroke syndrome of combined
      polar and paramedian thalamic infarction. METHODS: We studied combined polar
      paramedian thalamic infarction in 12 patients (6 right-sided lesions, 3 left
      sided lesions, and 3 bilateral lesions) who were selected from 208 consecutively
      registered patients with thalamic strokes in the Lausanne Stroke Registry.
      RESULTS: The clinical manifestation included executive dysfunction, apathy, and
      memory impairment in all patients, with eye movement disturbances in 10 patients
      (5 with right-sided lesions, 2 with left-sided lesions, 3 with bilateral
      lesions); acutely impaired consciousness in 11 patients (5 with right-sided
      lesions, 3 with left-sided lesions, 3 with bilateral lesions); aphasic
      disturbances in 8 patients (2 with right-sided lesions, 3 with left-sided
      lesions, 3 with bilateral lesions), including nonfluent aphasia in 1 patient
      (with left-sided lesions); dysarthria in 5 patients (4 with right-sided lesions,
      1 with bilateral lesions); constructional apraxia in 5 patients (with right-sided
      lesions); mild hemiparesis in 4 patients (2 with right-sided lesions, 2 with left
      sided lesions); dyscalculia in 3 patients (1 with left-sided lesions,1 with right
      sided lesions, 1 with bilateral lesions); limb dystonia or asterixis in 2
      patients (1 with right-sided lesions, 1 with bilateral lesions); mild hemisensory
      loss in 2 patients (1 with right-sided lesions, 1 with left-sided lesions);
      hemiataxia in 1 patient (with right-sided lesions); and ideomotor apraxia in 1
      patient (with left-sided lesions). Follow-up showed severely disabling,
      persistent amnesia in 7 patients (4 with right-sided lesions, 3 with bilateral
      lesions) and persistent eye movement dysfunction in 5 patients (2 with right
      sided lesions, 1 with left-sided lesions, 2 with bilateral lesions). The most
      common etiology appeared to be cardioembolism, followed by artery-to-artery
      embolism and presumed small-artery disease. CONCLUSIONS: Key features of this
      syndrome included amnesia preceded by a period of altered consciousness, and
      vertical eye movement disturbances. The severe and persistent amnesia may be due
      to coexisting damage to the anterior and dorsomedial nuclei.

PMID- 16087761
TI  - Effect of discontinuing aspirin therapy on the risk of brain ischemic stroke.
AB  - BACKGROUND: Aspirin, or acetylsalicylic acid, is widely used to prevent ischemic
      vascular disease. Clinical and experimental data suggest that a rebound effect
      occurs 4 or fewer weeks after interruption of aspirin therapy. OBJECTIVE: To
      study the discontinuation of aspirin therapy as a risk factor for ischemic stroke
      (IS). DESIGN: Case-control study. SETTING: Stroke unit. PARTICIPANTS: Three
      hundred nine patients with IS or transient ischemic attack undergoing long-term
      aspirin treatment before their index event and 309 age-, sex-, and antiplatelet
      therapy-matched controls who had not had an IS in the previous 6 months. METHODS:
      We compared the frequency of aspirin therapy discontinuation during the 4 weeks
      before an ischemic cerebral event in patients and the 4 weeks before interview in
      controls. RESULTS: The 2 groups had a similar frequency of risk factors, except
      for coronary heart disease, which was more frequent in patients (36% vs 18%; P <
      .001). Aspirin use had been discontinued in 13 patients and 4 controls. Aspirin
      interruption yielded an odds ratio for IS/transient ischemic attack of 3.4 (95%
      confidence interval, 1.08-10.63; P < .005) after adjustment in a multivariable
      model. CONCLUSIONS: These results highlight the importance of aspirin therapy
      compliance and give an estimate of the risk associated with the discontinuation
      of aspirin therapy in patients at risk for IS, particularly those with coronary
      heart disease.

PMID- 16087762
TI  - Pure monoparesis: a particular stroke subgroup?
AB  - BACKGROUND: Acute stroke presenting as monoparesis is rare, with a pure motor
      deficit in the arm or leg extending to an isolated facial paresis. OBJECTIVE: To
      raise the question if acute stroke presenting as monoparesis is a different
      entity from stroke with a more extensive motor deficit. PATIENTS: In the Lausanne
      Stroke Registry (1979-2000), 195 (4.1%) of 4802 patients met the clinical
      criteria for pure monoparesis involving the face (22%), arm (63%), or leg (15%).
      RESULTS: In the vast majority of cases (> 95%), monoparesis corresponded to
      ischemic stroke with a favorable outcome, with initial computed tomography scans
      or magnetic resonance images showing no signs of hemorrhage. The lesion for a
      facial deficit was most frequently located subcortically (internal capsule); for
      an arm deficit, in the superficial middle cerebral artery; and for a leg deficit,
      in the anterior cerebral artery territory. In pure monoparesis, only 17% of the
      patients had more than 1 risk factor as compared with 26% of those with bimodal
      and trimodal hemiparesis and with 46% of all patients with stroke other than
      those with pure motor stroke. The only frequent risk factor was hypertension
      (53%); however, this frequency was no different from that in other patients with
      stroke. No major stroke etiology could be identified in any of the 3 subgroups of
      monoparesis. CONCLUSION: Our finding of a wide range of stroke localization and
      etiology in monoparesis without any particular subgroup suggests that no specific
      plan of investigation can be recommended for these patients.

PMID- 16087763
TI  - Diffusion-weighted magnetic resonance imaging in symptomatic vertebrobasilar
      atherosclerosis and dissection.
AB  - BACKGROUND: Acute multiple brain infarction (AMBI) pattern on diffusion-weighted
      imaging (DWI) is associated with arterial and cardiac sources of embolism. The
      DWI characteristics of patients with stroke due to vertebrobasilar arterial
      dissection and atherosclerotic disease have not been reported in detail.
      OBJECTIVE: To describe the DWI stroke patterns in patients with posterior
      circulation occlusive disease to determine mechanisms of ischemia. DESIGN:
      Retrospective analysis of infarct patterns in patients with symptomatic
      vertebrobasilar disease. SETTING: Large community-based teaching hospital.
      PATIENTS: Patients admitted with stroke due to vertebrobasilar disease were
      identified retrospectively. Patients were included if DWI was obtained within 7
      days of symptom onset. MAIN OUTCOME MEASURE: Infarct patterns were analyzed
      according to established templates of vascular territories. RESULTS: Eleven
      patients with vertebral dissection and 39 patients with atherothrombosis were
      identified. An AMBI pattern was present in 8 (72%) of 11 patients with arterial
      dissections and 25 (64%) of 39 patients with atherosclerotic disease (P = .48).
      Distal embolism to the terminal branches of the basilar artery occurred with
      equal frequency in both groups and was found in half of all cases. Isolated
      thalamic infarction did not occur. Pontine infarction was noted in 2 (18%) of 11
      patients with dissections and 18 (46%) of 39 patients with atherosclerosis (P =
      .09). Cerebellar border zone involvement was found in 14 (36%) of 39 patients
      with atherosclerosis and 4 (37%) of 11 patients with dissections (P = .6).
      CONCLUSIONS: Large arterial disease is frequently associated with AMBI in the
      posterior circulation. The incidence of AMBI was comparable to that reported in
      the anterior circulation. This DWI study supports the importance of embolism as
      the main mechanism of infarction in patients with vertebrobasilar occlusive
      disease. On the basis of our experience, large-vessel vertebrobasilar disease
      rarely causes isolated small-vessel thalamic infarction.

PMID- 16087764
TI  - Mechanisms of recurrence in subtypes of ischemic stroke: a hospital-based follow
      up study.
AB  - BACKGROUND: Information on the mechanism of recurrent stroke may help physicians
      treating patients with ischemic stroke. However, the mechanisms of recurrence in
      each stroke subtype are not well known, especially in Asians. OBJECTIVE: To
      compare the mechanisms of the index and recurrent stroke. DESIGN: Analysis of
      data from a prospective acute stroke registry. SETTING: University hospital.
      PATIENTS: Using the clinical syndrome, diffusion-weighted imaging, and vascular
      studies, we divided 901 patients into 5 groups: large-artery atherosclerosis,
      cardioembolism, small-artery disease, parent-artery disease occluding the deep
      perforators, and no determined cause. The patients with large-artery
      atherosclerosis were subdivided into 2 groups: intracranial and extracranial.
      MAIN OUTCOME MEASURES: The mechanisms of recurrent vascular events (strokes or
      coronary heart disease) in subtypes of ischemic stroke were compared. RESULTS:
      Ninety-three recurrent vascular events (86 strokes and 7 instances of coronary
      heart disease) were evaluated. The pattern of recurrent stroke differed for the
      intracranial and extracranial groups; unlike the patients with intracranial large
      artery atherosclerosis, recurrent strokes in the extracranial group were often
      unpredictable with respect to the site of recurrence and degree of preexisting
      stenosis. None of the patients in the extracranial group had recurrences that
      were caused by intracranial large-artery atherosclerosis or vice versa. In
      patients with small-artery disease and stroke with no determined cause,
      intracranial stenosis was often found at the time of recurrence. CONCLUSIONS:
      From prognostic and therapeutic perspectives, patients with atherosclerosis
      should be divided into those with intracranial large-artery atherosclerosis and
      extracranial large-artery atherosclerosis. In addition, intracranial large-artery
      atherosclerosis may be important in the development of small-artery disease and
      stroke with no determined cause, especially in the population with a higher
      frequency of intracranial large-artery atherosclerosis.

PMID- 16087765
TI  - Sudden uncontrollable somnolence and medication use in Parkinson disease.
AB  - BACKGROUND: Episodes of sudden uncontrollable somnolence have been reported in
      patients with Parkinson disease (PD) receiving dopamine agonists, including
      pramipexole and ropinirole, but controversy persists concerning their nature,
      severity, and frequency. OBJECTIVES: To quantify the risk of sudden
      uncontrollable somnolence in patients taking specific PD medications and to
      define its predictors. METHODS: We contacted 929 patients with PD and
      administered a 45- to 60-minute interview addressing medication use, adverse
      events, and the patient's clinical status in the preceding 6 months. Their
      physicians completed record reviews detailing their clinical histories and drug
      regimens. The outcome of interest in this case-control study was an episode of
      somnolence that was uncontrollable, severe, and inappropriate, such as while
      driving or engaged in social activity. For multiple events, the first was chosen
      as the index event. For each case, we sampled control time from all respondents
      who had no event as of the index time for that case. Multiple logistic regression
      was used to adjust for potential confounders. RESULTS: Episodes of uncontrollable
      somnolence were reported by 22% of all respondents. After controlling for age,
      sex, PD duration and severity, frailty, and other medication use, we found that
      patients receiving a dopamine agonist (pramipexole, ropinirole, or pergolide)
      were nearly 3-fold as likely to have episodes of sudden uncontrollable somnolence
      (odds ratio, 2.8; 95% confidence interval, 1.8-4.2) compared with all other PD
      medication users. Similar risks were seen for the 3 agents, pramipexole,
      ropinirole, and pergolide, each compared with levodopa alone (odds ratio, 2.2,
      1.8, and 2.1, respectively), with a clear dose-response relationship for each. No
      increase in risk was seen with any other drugs studied. CONCLUSIONS: Dopamine
      agonists widely used for the management of PD significantly increase the risk of
      sudden uncontrollable somnolence in a dose-related manner. Greater attention to
      this potentially serious adverse effect will be necessary to improve the safety
      of use of this important category of PD drugs.

PMID- 16087766
TI  - Identification of a novel founder mutation in the DYSF gene causing clinical
      variability in the Spanish population.
AB  - BACKGROUND: Mutations in the dysferlin (DYSF) gene cause 3 different phenotypes
      of muscular dystrophies: Miyoshi myopathy, limb-girdle muscular dystrophy type
      2B, and distal anterior compartment myopathy. OBJECTIVE: To present the results
      of clinical and molecular analysis of 8 patients with dysferlinopathy from 5
      unrelated families. DESIGN: Clinical assessment was performed with a standardized
      protocol. A muscle biopsy specimen was obtained and studied by
      immunohistochemistry. Genetic analysis was performed using single-stranded
      conformation polymorphism and direct sequencing of genomic DNA. RESULTS: All the
      patients presented the R1905X mutation in the DYSF gene in homozygosity, and the
      haplotype analysis at the DYSF locus revealed that it was a novel and founder
      mutation. A C-to-T transition at nucleotide position 6086 changes an arginine
      into a stop codon, leading to premature termination of translation. This mutation
      was expressed as 3 different clinical phenotypes (limb-girdle muscular dystrophy
      type 2B, Miyoshi distal myopathy, and distal anterior dysferlinopathy), but only
      1 phenotype was found in the same family. CONCLUSIONS: The new R1905X DYSF
      founder mutation produced the 3 possible dysferlinopathy phenotypes without
      intrafamilial heterogeneity. This homogeneous population in Sueca, Spain, should
      be helpful in studying the modifying factors responsible for the phenotypic
      variability.

PMID- 16087767
TI  - Prognosis of Parkinson disease: risk of dementia and mortality: the Rotterdam
      Study.
AB  - BACKGROUND: Most prognostic studies on Parkinson disease have been hospital based
      or have applied register-based case-finding methods. Potential under
      representation of mild cases may have given biased results. OBJECTIVE: To
      evaluate whether Parkinson disease is associated with an increased risk of
      dementia and death. DESIGN: Population-based cohort study. Parkinson disease and
      dementia were assessed through in-person examination at baseline (1990-1993) and
      2 follow-up visits (1993-1994 and 1997-1999). Computerized linkage to medical and
      municipality records provided additional information on disease outcomes and
      mortality. SETTING: General population. PARTICIPANTS: A total of 6969
      participants, including 99 prevalent and 67 incident cases of Parkinson disease.
      MAIN OUTCOME MEASURES: Incident dementia and death. Adjusted hazard ratios were
      calculated through Cox proportional hazards regression analysis. RESULTS:
      Patients with Parkinson disease had an increased risk of dementia (hazard ratio,
      2.8; 95% confidence interval, 1.8-4.4), which was especially pronounced in
      participants carrying at least 1 apolipoprotein E gene (APOE) epsilon2 allele
      (13.5; 4.5-40.6). Parkinson disease was associated with an increased mortality
      risk (1.8; 1.5-2.3). The association consistently diminished when analyses were
      sequentially restricted to patients with shorter disease duration and after
      adjustment for the occurrence of dementia. CONCLUSIONS: Especially patients with
      Parkinson disease who carry an APOE epsilon2 allele have an increased risk of
      developing dementia. Increased mortality risk in Parkinson disease is dependent
      on disease duration and is only modest in the absence of dementia.

PMID- 16087768
TI  - A positron emission tomographic study in spontaneous migraine.
AB  - BACKGROUND: Functional brain imaging in acute migraine has proved challenging
      because of the logistic problems associated with an episodic condition. Since the
      seminal observation of brainstem activation in migraine, there has been only a
      single case substantiating this finding. OBJECTIVE: To test the hypothesis that
      brainstem activation could be detected in migraine and to refine the anatomic
      localization with higher-resolution positron emission tomography than previously
      used. DESIGN: Using positron emission tomography with radioactive water
      (H(2)15O), we studied acute migraine attacks occurring spontaneously. Five
      patients underwent imaging in ictal and interictal states, and the differences
      were analyzed by means of statistical parametric mapping. SETTING: Tertiary
      referral center. PATIENTS: Six volunteers with episodic migraine were recruited
      from advertisements in migraine newsletters. One patient was excluded because of
      use of preventive medication. MAIN OUTCOME MEASURE: Brainstem activation during
      migraine state vs interictal state. RESULTS: Two patients had a typical
      migrainous aura before the onset of the headache. All of the attacks studied
      fulfilled standard diagnostic criteria for migraine. Comparing the migraine scans
      with interictal scans, there was significant activation in the dorsal pons,
      lateralized to the left (small volume correction, P = .003). Activation was also
      seen in the right anterior cingulate, posterior cingulate, cerebellum, thalamus,
      insula, prefrontal cortex, and temporal lobes. There was an area of deactivation
      in the migraine phase also located in the pons, lateralized to the right.
      CONCLUSIONS: Our findings provide clear evidence of dorsal pontine activation in
      migraine and reinforce the view that migraine is a subcortical disorder
      modulating afferent neural traffic.

PMID- 16087769
TI  - Dopamine transporter positron emission tomography in spinocerebellar ataxias type
      1, 2, 3, and 6.
AB  - BACKGROUND: The spinocerebellar ataxias (SCAs) are a genetically heterogeneous
      group of autosomal dominant ataxias: some mutations, including SCA1, SCA2, and
      SCA3, are multisystemic disorders characterized by a variety of noncerebellar
      symptoms while others, like SCA6, give rise to a pure cerebellar syndrome.
      OBJECTIVE: To identify impairments of the dopaminergic system and regional
      changes of glucose metabolism in SCA1, SCA2, SCA3, and SCA6. METHODS: We used
      [11C]d-threo-methylphenidate and [18F]fluorodeoxyglucose positron emission
      tomography to identify cerebral dopamine terminal loss and specific regional
      metabolic patterns in SCA1, SCA2, SCA3, and SCA6. RESULTS: The binding potential
      of [11C]d-threo-methylphenidate was reduced in the striatum in SCA2 and SCA3; in
      contrast to patients with Parkinson disease, no increased susceptibility of the
      putamen was evident. Decreased regional cerebral glucose metabolism was found in
      the cerebellum of all patients with SCA, the brainstem of SCA1, SCA2, SCA3, the
      thalamus and putamen of SCA3, and the parietal cortex of patients with SCA2. A
      trend toward increased regional cerebral glucose metabolism was found in the
      temporal cortex of all patients with SCA, pronounced in SCA6. CONCLUSIONS:
      Specific biochemical patterns point to different mechanisms of neuronal
      dysfunction in SCA1, SCA2, SCA3, and SCA6; dopamine terminal loss is severe in
      SCA2 but distinct from Parkinson disease.

PMID- 16087770
TI  - Paroxysmal apnea and vasomotor instability following medullary infarction.
AB  - BACKGROUND: Central hypoventilation and paroxysmal hypertension are uncommon
      complications of medullary infarction. To our knowledge, the combination of these
      autonomic complications of medullary stroke has not previously been reported.
      OBJECTIVE: To describe a patient who experienced life-threatening paroxysmal
      attacks of central apnea and vasomotor instability 3 months after medullary
      infarction, a combination of symptoms that is unusual. PATIENT, METHODS, AND
      RESULTS: Following a right lateral medullary infarction, an otherwise stable 70
      year-old woman developed recurrent episodes of apnea (PCO2), > 100 mm Hg), blood
      pressure instability (systolic blood pressure, > 200 to < 100 mm Hg), and mental
      status changes (from agitation to coma) within hours of removal from mechanical
      ventilation. These attacks occurred repeatedly after removal from mechanical
      ventilation and were prevented by diaphragm pacing with a phrenic nerve pacemaker
      and nocturnal mechanical ventilation via a tracheostomy. CONCLUSIONS: A syndrome
      of life-threatening central hypoventilation and vasomotor instability can occur
      after medullary infarction. Placement of a phrenic nerve pacemaker can prevent
      these complications, without the functional limitations imposed by continuous
      mechanical ventilation.

PMID- 16087771
TI  - Pleuropulmonary fibrosis after long-term treatment with the dopamine agonist
      pergolide for Parkinson Disease.
AB  - Dopamine agonists are increasingly used in the treatment of Parkinson disease,
      but they may cause serious adverse effects. In December 1983, symptoms of
      Parkinson disease developed in a 55-year-old man with no history of pulmonary
      disease, smoking, or asbestos exposure. He began treatment with dopamine agonists
      bromocriptine mesylate (in 1984) and pergolide mesylate (in 1989). In late 2000,
      pulmonary symptoms developed. Chest radiographs and computed tomographic findings
      showed a mass in the right upper lobe and effusion. A biopsy specimen showed
      pleural and parenchymal fibrosis. This syndrome resolved after cessation of
      pergolide therapy and a switch to pramipexole dihydrochloride. This case draws
      attention to the association of long-term ergot dopamine agonist therapy with
      pleuropulmonary fibrosis, which can develop as late as 11 years after the
      initiation of therapy. We also review evidence that the risk of this complication
      is substantially lower with the newer nonergot dopamine agonists.

PMID- 16087772
TI  - Anti-GAD antibodies and periodic alternating nystagmus.
AB  - BACKGROUND: Autoantibodies directed against glutamic acid decarboxylase (GAD-Ab)
      have recently been described in a few patients with progressive cerebellar
      ataxia, suggesting an autoimmune physiopathologic mechanism. OBJECTIVE: To
      determine the exact role of GAD-Ab and gamma-aminobutyric acid (GABA)-ergic
      neurotransmission in the pathogenesis of cerebellar ataxia. DESIGN: Case report.
      SETTING: University neurological hospital. PATIENT: We report the case of a
      patient with subacute cerebellar ataxia associated with GAD-Ab showing periodic
      alternating nystagmus (PAN). INTERVENTION: Baclofen, a GABAergic medication, was
      given to the patient. MAIN OUTCOME MEASURES: Eye movement recording of
      spontaneous nystagmus and postrotatory vestibular responses. RESULTS: Baclofen
      was effective in suppressing PAN and improving postrotatory vestibular responses
      but not for improving cerebellar ataxia. CONCLUSION: The presence of PAN and the
      response to baclofen provide a unique opportunity to suggest a direct role of GAD
      Ab in cerebellar dysfunction in this patient.

PMID- 16087773
TI  - Maternal complex partial seizure associated with fetal distress.

PMID- 16087774
TI  - Large paraspinal and iliopsoas muscle hematomas.

PMID- 16087775
TI  - Cerebral syphilitic gumma in a human immunodeficiency virus-positive patient.

PMID- 16087776
TI  - Acute hebephrenia.

PMID- 16087777
TI  - Myotonic dystrophy.

PMID- 16087778
TI  - Reexamination of the TEMPO Study.

PMID- 16087779
TI  - Evaluation of vascular function in apolipoprotein E knockout mice with
      angiotensin-dependent renovascular hypertension.
AB  - It is known that the endothelial function is compromised in atherosclerosis and
      arterial hypertension and that angiotensin is an important factor contributing to
      both pathophysiologies. The aim of this study was to evaluate the vascular
      function in a hypercholesterolemia/atherosclerosis model, in the angiotensin II
      dependent 2-kidney 1-clip (2K1C) hypertension model and when both conditions
      coexist. Eight-week-old apolipoprotein E knockout (apoE; n=20) and C57BL/6 (C57;
      n=20) mice underwent a 2K1C or sham operation and were studied 28 days later.
      Mean arterial pressure was higher in apoE-2K1C and C57-2K1C (126+/-3 and 128+/-3
      mm Hg) when compared with the apoE-Sham and C57-Sham (103+/-2 and 104+/-2 mm Hg,
      respectively; P<0.05). The vascular reactivity to norepinephrine (NE; 10(-9) to 2
      x 10(-3) mol/L), acetylcholine (ACh), and sodium nitroprusside (SNP; 10(-10) to
      10(-3) mol/L) was evaluated in the mesenteric arteriolar bed through
      concentration-effect curves. NE caused vascular hyper-reactivity in apoE-Sham,
      apoE-2K1C, and C57-2K1C (maximal response 146+/-5, 144+/-5, and 159+/-4 mm Hg,
      respectively) compared with C57-Sham (122+/-7 mm Hg; P<0.05). The ACh-induced
      relaxation was smaller (P<0.05) in apoE-2K1C and C57-2K1C (maximal response 53+/
      3% and 46+/-3%) than in apoE-Sham and C57-Sham mice (78+/-5% and 73+/-4%). SNP
      induced vascular relaxation showed similar concentration-effect curves in all
      groups. We conclude that in C57-2K1C mice, the increased reactivity to NE and the
      decreased endothelium-dependent relaxation contribute to the maintenance of
      hypertension. The apoE mouse, at early stages of atherosclerosis, shows hyper
      reactivity to NE but does not have endothelium dysfunction yet. However, the
      concurrence of both pathophysiologies does not result in additive effects on the
      vascular function.

PMID- 16087780
TI  - Short-term angiotensin(1-7) receptor MAS stimulation improves endothelial
      function in normotensive rats.
AB  - In this study we evaluated the effect of angiotensin(1-7) and its nonpeptide
      analog, AVE 0991, on the endothelial function in vivo. The experiments were
      performed in conscious adult male Wistar rats, with polyethylene catheters
      implanted into the descending aorta (through left carotid artery), for injection
      of acetylcholine or sodium nitroprusside, femoral artery for mean arterial
      pressure and heart rate measurement; and femoral vein for drug administration.
      Increasing doses of acetylcholine (3.1 ng to 25.0 ng) or nitroprusside (1.0
      microg to 10.0 microg) were administered before and 30 minutes after the start of
      the infusion of: angiotensin(1-7) (0.7 and 7.0 pmol/min); A-779 (180 pmol/min);
      angiotensin(1-7) (7.0 pmol/min) combined with A-779 (180 pmol/min); AVE 0991 (11,
      45, and 230 pmol/min); AVE 0991 (45 pmol/min) combined with A-779 (180 pmol/min),
      or vehicle (6 microL/min). Baseline mean arterial pressure and heart rate were
      not altered during angiotensin(1-7) or AVE 0991 infusion. Angiotensin(1-7) (0.7
      pmol/min) infusion produced a significant potentiation of the hypotensive effect
      of acetylcholine (3.1 ng: -9+/-1 mm Hg before; -18+/-2 mm Hg after; P<0.05). A
      similar potentiation was observed with the higher dose of angiotensin(1-7). As
      observed for angiotensin(1-7), infusion of AVE 0991 at 230 pmol/min potentiated
      the acetylcholine effect (3.1 ng: -8+/-2 mm Hg before; -16+/-2 mm Hg after;
      P<0.05). The potentiating effect was not observed for nitroprusside. A-779 or l
      NAME treatment blocked the potentiation produced by angiotensin(1-7) or AVE 0991.
      Our data indicate that short-term stimulation of angiotensin(1-7) receptors
      improve endothelial function through facilitation of nitric oxide release.

PMID- 16087781
TI  - Detection of angiotensin II in supernatants of stimulated mononuclear leukocytes
      by matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass
      analysis.
AB  - Angiotensin II (Ang II) is the major vasoactive component of the renin
      angiotensin system. Several components of the renin-angiotensin system have been
      demonstrated in different tissues. Whereas the roles of tissue and renal renin
      angiotensin system have been studied in detail, much less is known on whether the
      corpuscular elements of circulating blood contribute to Ang II production. Here
      we examined whether, in addition to vasculature, blood cells also contribute to
      the circulating Ang II levels. Mononuclear leukocytes were obtained from healthy
      subjects and were incubated. The resulting supernatant was chromatographed using
      different chromatographic methods. The vasoconstrictive effects of aliquots of
      the resulting fractions were tested. Each fraction with a vasoconstrictive effect
      was analyzed by mass spectrometry. In one fraction with a strong vasoconstrictive
      effect, Ang II was identified. Mononuclear lymphocytes produced Ang II in amounts
      sufficient to stimulate Ang II type 1 receptors. Moreover, in mononuclear
      leukocytes, renin as well as angiotensin-converting enzyme mRNA expression was
      detectable by RT-PCR. These findings demonstrate that mononuclear leukocytes are
      a source of Ang II. Ang II secretion by these cells may play a significant role
      in humoral vascular regulation. In conclusion, the isolation of Ang II in
      supernatants of mononuclear leukocytes adds a further physiological source of Ang
      II to the current view of angiotensin metabolism. The quantitative role of
      lymphocyte-derived Ang II secretion compared with the other sources of Ang II
      should be defined further, but the release found under the present conditions is
      at least sufficient to elicit vasoconstrictive effects.

PMID- 16087782
TI  - Regulation of discoidin domain receptor 2 by cyclic mechanical stretch in
      cultured rat vascular smooth muscle cells.
AB  - Discoidin domain receptor 2 (DDR2) plays potential roles in the regulation of
      collagen turnover mediated by smooth muscle cells in atherosclerosis. How
      mechanical stretch affects the regulation of DDR2 in smooth muscle cells is not
      fully understood. We sought to investigate the cellular and molecular mechanisms
      of regulation of DDR2 by cyclic stretch in smooth muscle cells. Rat vascular
      smooth muscle cells grown on a flexible membrane base were stretched by vacuum to
      20% of maximum elongation, at 60 cycles/min. Cyclic stretch significantly
      increased DDR2 protein and mRNA expression after stretch. Cyclic stretch also
      significantly increased DNA-protein binding activity of Myc-Max. Addition of
      SB203580, transforming growth factor-beta1 (TGF-beta1) monoclonal antibody, p38
      small interfering RNA (siRNA), and c-myc siRNA 30 minutes before stretch
      inhibited the induction of DDR2 protein and abolished the DNA-protein binding
      activity induced by cyclic stretch. Cyclic stretch increased, whereas SB203580
      abolished the phosphorylated p38 protein. Conditioned medium from stretched
      smooth muscle cells and exogenous administration of angiotensin II and TGF-beta1
      recombinant proteins to the nonstretched cells increased DDR2 protein expression
      similar to that seen after stretch. In conclusion, cyclic mechanical stretch
      enhances DDR2 expression in cultured rat smooth muscle cells. The stretch-induced
      DDR2 is mediated by angiotensin II and TGF-beta1, at least in part, through p38
      mitogen-activated protein kinase and Myc pathway.

PMID- 16087783
TI  - Arterial compression of the retro-olivary sulcus of the ventrolateral medulla in
      essential hypertension and diabetes.
AB  - Pulsatile arterial compression in the retro-olivary sulcus along the surface of
      the ventrolateral medulla has been postulated as a mechanism in both essential
      hypertension and diabetes. The objective of this study was to test the
      independent effect of arterial compression in the retro-olivary sulcus on each of
      these diseases, using separate logistic regression models to control for other
      known risk factors. Study design was case-control. The study population consisted
      of 147 consecutive patients treated for neurological conditions requiring MRI of
      the posterior cranial fossa. Information on essential hypertension, diabetes, and
      risk factors for each disease was abstracted from medical records. Presence of
      arterial compression was determined by blinded review of magnetic resonance
      images. In the essential hypertension analysis, odds of arterial compression
      among hypertensive patients were 2.99-times the odds among normotensive subjects
      (P=0.04), controlling for hypertension risk factors such as age, body mass index,
      race, diabetes, and family history of hypertension. Of compressed hypertensive
      subjects, 56% were compressed on the left and 44% were compressed on the right.
      In the diabetes analysis, odds of arterial compression among diabetic subjects
      were 1.14-times the odds among nondiabetic subjects (P=0.83). Of compressed
      diabetic subjects, 60% were compressed on the left, and 40% were compressed on
      the right. Results suggest that arterial compression of the retro-olivary sulcus
      may be an independent risk factor for essential hypertension in this population,
      supporting the postulate for a treatable (with microvascular decompression)
      neural mechanism for essential hypertension. However, in the diabetic population,
      the slight increase in the odds of arterial compression was not significant.

PMID- 16087784
TI  - Diuresis and natriuresis caused by activation of VR1-positive sensory nerves in
      renal pelvis of rats.
AB  - To test the hypothesis that activation of the vanilloid receptor 1 (VR1)
      expressed in sensory nerves innervating the renal pelvis leads to diuresis and
      natriuresis, a selective VR1 receptor agonist, capsaicin (2.4 nmol), or vehicle
      was perfused intravenously or into the left renal pelvis of anesthetized rats at
      a rate without changing renal perfusion pressure. Mean arterial pressure was not
      altered by capsaicin administered intravenously or into the renal pelvis.
      Capsaicin perfusion into the left renal pelvis but not intravenously caused
      significant increases in urine flow rate and urinary sodium excretion bilaterally
      in a dose-dependent manner, which were abolished by capsazepine, a selective VR1
      receptor antagonist, given ipsilaterally to the renal pelvis or by ipsilateral
      renal denervation. Capsaicin given intravenously or into the left renal pelvis
      increased plasma calcitonin gene-related peptide levels to the same extent.
      Increased plasma calcitonin gene-related peptide levels induced by capsaicin
      (68.9+/-2.8 pg/mL) perfusion into the renal pelvis was prevented either by
      capsazepine (22.5+/-10.1 pg/mL) given ipsilaterally into the renal pelvis or by
      ipsilateral renal denervation (25.9+/-2.3 pg/mL). Taken together, our data show
      that unilateral activation of VR1-positive sensory nerves innervating the renal
      pelvis leads to bilateral diuresis and natriuresis via a mechanism that is
      independent of plasma calcitonin gene-related peptide levels. These data suggest
      that VR1-positive sensory nerves in the kidney enhance renal excretory function,
      a mechanism that may be critically involved in sodium and fluid homeostasis.

PMID- 16087785
TI  - Effects of captopril on the renin angiotensin system, oxidative stress, and
      endothelin in normal and hypertensive rats.
AB  - There is substantial evidence suggesting that angiotensin II plays an important
      role in elevating blood pressure of spontaneously hypertensive rats, despite
      normal plasma renin activity, and that converting enzyme inhibitors (captopril)
      can effectively normalize blood pressure in the spontaneously hypertensive rats.
      One mechanism by which angiotensin II induces hypertension is via oxidative
      stress and endothelin, as seen in subpressor angiotensin II-induced hypertension.
      In fact, it has been shown that antioxidants lower mean arterial pressure in
      spontaneously hypertensive rats. However, the relationship between angiotensin
      II, oxidative stress, and endothelin in the spontaneously hypertensive rats is
      still relatively undefined. This study examines the relationship between mean
      arterial pressure, plasma renin activity, angiotensin II, oxidative stress, and
      endothelin in spontaneously hypertensive rats compared with normotensive Wistar
      Kyoto rats, and the effects of captopril on this association. Untreated
      spontaneously hypertensive rats had increased plasma angiotensin II levels
      despite normal plasma renin activity, oxidative stress, and endothelin. Captopril
      treatment in spontaneously hypertensive rats lowered mean arterial pressure,
      angiotensin II, oxidative stress, and endothelin, and increased plasma renin
      activity. In contrast, captopril increased plasma renin activity (suggesting
      effective captopril treatment) but did not significantly alter mean arterial
      pressure, angiotensin II, oxidative stress, or endothelin of Wistar Kyoto rats.
      These results suggest that in spontaneously hypertensive rats, angiotensin II is
      a primary instigator of hypertension, and that captopril selectively lowers
      angiotensin II, oxidant stress, and endothelin, which in turn may contribute to
      the blood pressure-lowering efficacy of captopril in spontaneously hypertensive
      rats.

PMID- 16087786
TI  - Aldosterone stimulates collagen gene expression and synthesis via activation of
      ERK1/2 in rat renal fibroblasts.
AB  - Recently, we demonstrated that in rats treated chronically with aldosterone and
      salt, severe tubulointerstitial fibrosis is associated with the activation of
      mitogen-activated protein kinases (MAPKs), including extracellular signal
      regulated kinases (ERK1/2). Here, we investigated whether aldosterone stimulates
      collagen synthesis via ERK1/2-dependent pathways in cultured rat renal
      fibroblasts. Gene expression of mineralocorticoid receptor (MR) and types I, II,
      III, and IV collagen was measured by real-time polymerase chain reaction (PCR).
      MR protein expression and ERK1/2 activity were evaluated by Western blotting
      analysis with anti-MR and anti-phospho-ERK1/2 antibodies, respectively. Collagen
      synthesis was determined by [3H]-proline incorporation. Significant levels of MR
      mRNA and protein expression were observed in rat renal fibroblasts. Treatment
      with aldosterone (0.1 to 10 nmol/L) increased ERK1/2 phosphorylation in a
      concentration-dependent manner with a peak at 5 minutes. Aldosterone (10 nmol/L)
      also increased the mRNA levels of types I, III, and IV collagen at 36 hours but
      had no effect on the type II collagen mRNA level. [3H]-proline incorporation was
      significantly increased by aldosterone in both the medium and cell layer at 48
      hours. Aldosterone-induced ERK1/2 phosphorylation was markedly attenuated by
      pretreatment with eplerenone (10 micromol/L), a selective MR antagonist, or
      PD98059 (10 micromol/L), a specific inhibitor of MAPK kinase/ERK kinase, which is
      the upstream activator of ERK1/2. In addition, both eplerenone and PD98059
      prevented the aldosterone-induced increases in types I, III, and IV collagen mRNA
      and [3H]-proline incorporation. These results suggest that aldosterone stimulates
      collagen gene expression and synthesis via MR-mediated ERK1/2 activation in renal
      fibroblasts, which may contribute to the progression of aldosterone-induced
      tubulointerstitial fibrosis.

PMID- 16087787
TI  - Effects of time of day of treatment on ambulatory blood pressure pattern of
      patients with resistant hypertension.
AB  - Patients with resistant hypertension present high prevalence of a non-dipper
      blood pressure pattern. Recent results indicate that non-dipping is related
      partly to the absence of 24-hour therapeutic coverage in patients treated with
      single morning doses. Accordingly, we investigated the impact of treatment time
      on the blood pressure pattern in 700 patients with resistant hypertension on the
      basis of clinic measurements who were studied by 48-hour ambulatory monitoring.
      Among them, 299 patients received all their medication on awakening, and 401 were
      taking > or =1 antihypertensive drug at bedtime. The percentage of patients with
      controlled ambulatory blood pressure was double in patients taking 1 drug at
      bedtime (P=0.008). Among the 578 patients with true resistant hypertension,
      subjects receiving 1 drug at bedtime showed a significant reduction in the 24
      hour mean of systolic and diastolic blood pressure (3.1 and 1.6 mm Hg,
      respectively; P<0.011). This reduction was much more prominent during nighttime
      (5.1 and 3.0 mm Hg; P<0.001). Accordingly, the diurnal/nocturnal blood pressure
      ratio was significantly increased by 2.7 and the prevalence on non-dipping
      reduced (56.9 versus 81.9%; P<0.001) in patients taking 1 drug at bedtime.
      Compared with patients receiving all drugs on awakening, subjects with 1 drug at
      bedtime also showed significant reductions in the average values of glucose,
      cholesterol, fibrinogen, and urinary albumin excretion (P<0.011). In patients
      with resistant hypertension, pharmacological therapy should take into account
      when to treat with respect to the rest-activity cycle of each patient to improve
      control and to avoid the non-dipper pattern associated to higher cardiovascular
      risk.

PMID- 16087788
TI  - Differing administration time-dependent effects of aspirin on blood pressure in
      dipper and non-dipper hypertensives.
AB  - Aspirin is a potent antioxidative agent that reduces vascular production of
      superoxide, prevents angiotensin II-induced hypertension, and induces NO release.
      Low-dose aspirin administered at bedtime, but not on awakening, has also been
      shown to reduce blood pressure, possibly enhancing the nocturnal trough in NO
      production. Because endothelium-dependent vasodilation is blunted through a
      decrease in NO release in non-dipper compared with dipper patients, we compared
      the administration time-dependent influence of aspirin on ambulatory blood
      pressure in dipper and non-dipper hypertensive subjects. We studied 257 patients
      with mild hypertension (98 men and 159 women), 44.6+/-12.5 years of age, randomly
      assigned to receive 100 mg per day of aspirin either on awakening or at bedtime.
      Ambulatory blood pressure was measured for 48 hours at baseline and after 3
      months of intervention. Blood pressure was slightly elevated after aspirin on
      awakening (increase of 1.5/1.0 mm Hg in the 24-hour mean of systolic/diastolic
      blood pressure; P<0.028). A highly significant blood pressure reduction was
      observed in patients who received aspirin at bedtime (decrease of 7.2/4.9 mm Hg
      in systolic/diastolic blood pressure; P<0.001). The reduction in nocturnal blood
      pressure mean was double in non-dippers (11.0/7.1 mm Hg) compared with dippers
      (5.5/3.3 mm Hg; P<0.001). This prospective trial corroborates the significant
      administration time-dependent effect of low-dose aspirin on blood pressure,
      mainly in non-dipper hypertensive patients. The timed administration of low-dose
      aspirin could thus provide a valuable approach, beyond prevention of
      cardiovascular disease, in the blood pressure control of patients with mild
      hypertension.

PMID- 16087789
TI  - Aldosterone stimulates vascular smooth muscle cell proliferation via big mitogen
      activated protein kinase 1 activation.
AB  - The nongenomic effects of aldosterone have been implicated in the pathogenesis of
      various cardiovascular diseases. Aldosterone-induced nongenomic effects are
      attributable in part to the activation of extracellular signal-regulated kinase
      1/2 (ERK1/2), a classical mitogen-activated protein (MAP) kinase. Big MAP kinase
      1 (BMK1), a newly identified MAP kinase, has been shown to be involved in cell
      proliferation, differentiation, and survival. We examined whether aldosterone
      stimulates BMK1-mediated proliferation of cultured rat aortic smooth muscle cells
      (RASMCs). Mineralocorticoid receptor (MR) expression and localization were
      evaluated by Western blotting analysis and fluorolabeling methods. ERK1/2 and
      BMK1 activities were measured by Western blotting analysis with the respective
      phosphospecific antibodies. Cell proliferation was determined by Alamar Blue
      colorimetric assay. Aldosterone (0.1 to 100 nmol/L) dose-dependently activated
      BMK1 in RASMCs, with a peak at 30 minutes. To clarify whether aldosterone-induced
      BMK1 activation is an MR-mediated phenomenon, we examined the effect of
      eplerenone, a selective MR antagonist, on aldosterone-induced BMK1 activation.
      Eplerenone (0.1 to 10 micromol/L) dose-dependently inhibited aldosterone-induced
      BMK1 activation in RASMCs. Aldosterone also stimulated RASMC proliferation, which
      was inhibited by eplerenone. Aldosterone-mediated phenomena were concluded to be
      attributable to a nongenomic effect because cycloheximide failed to inhibit
      aldosterone-induced BMK1 activation. Transfection of dominant-negative MAP
      kinase/ERK kinase 5 (MEK5), which is an upstream regulator of BMK1, partially
      inhibited aldosterone-induced RASMC proliferation, which was almost completely
      inhibited by MEK inhibitor PD98059. In addition to the classical steroid
      activity, rapid nongenomic effects induced by aldosterone may represent an
      alternative etiology for vascular diseases such as hypertension.

PMID- 16087790
TI  - Native C-reactive protein increases whereas modified C-reactive protein reduces
      atherosclerosis in apolipoprotein E-knockout mice.
AB  - BACKGROUND: C-reactive protein (CRP) may have proatherogenic but also
      vasoprotective properties. We tested the hypothesis that the configuration of CRP
      (pentameric, or native [nCRP], versus monomeric, or modified [mCRP]) determines
      these different characteristics in an in vivo model. METHODS AND RESULTS: We
      investigated the effects of human nCRP and mCRP on the development of
      atherosclerosis in apolipoprotein E-knockout (ApoE(-/-)) mice. Treatment with
      nCRP for 8 weeks (2.5 mg/kg SC weekly) resulted in a 4-fold-higher mean aortic
      plaque area in 14-week-old female ApoE(-/-) mice compared with the saline
      controls. In contrast, mean plaque size was decreased by approximately 50% in
      mCRP-treated ApoE(-/-) mice (2.5 mg/kg SC weekly). Using immunohistochemistry, we
      report the natural presence of the mCRP antigen in saline controls. mCRP antigen
      was expressed in smooth muscle cells and extracellularly in the vicinity of the
      plaques to a similar level in both CRP-treated groups and saline controls. mCRP
      and ApoB colocalized with macrophages and were equally upregulated in all aortic
      plaques. Vascular cell adhesion molecule expression was increased, and CD154 and
      intercellular adhesion molecule showed a trend for higher expression in nCRP
      treated compared with mCRP-treated mice. CD154 expression in the vessel wall and
      plaque size correlated significantly. mCRP-treated ApoE(-/-) exhibited higher
      serum levels of the antiinflammatory interleukin-10 compared with the other 2
      groups. CONCLUSIONS: Here, we show that mCRP and nCRP have opposite effects on
      atherosclerosis in ApoE(-/-) mice. These data may explain in part the conflicting
      activities previously reported for CRP in models of atherogenesis.

PMID- 16087791
TI  - Contribution of cyclooxygenase-2 to elevated biosynthesis of thromboxane A2 and
      prostacyclin in cigarette smokers.
AB  - BACKGROUND: Cigarette smoking is highly pathogenic to the vasculature. In
      smokers, the biosynthesis of both thromboxane (Tx) A2 and prostacyclin is
      increased. We hypothesized that the excess in prostacyclin biosynthesis in
      smokers was derived from the inducible cyclooxygenase-2 (COX-2). We further
      hypothesized that if the overproduction of prostacyclin in smokers were
      restraining platelet activation, then inhibition of COX-2 would lead to an
      increase in the activation of platelets, with a corresponding increase in the
      biosynthesis of TxA2. METHODS AND RESULTS: Smokers and nonsmokers received
      rofecoxib 25 mg twice daily or placebo for 1 week each in random sequence. The
      systemic biosynthesis of TxA2 and prostacyclin was assessed by analysis of their
      respective urinary metabolites, 11-dehydrothromboxane B2 (Tx-M) and 2'3-donor-6
      keto-PGF(1alpha) (PGI-M). Serum TxB2 was measured as an indicator of platelet COX
      1 activity. Results are expressed as mean+/-SE with median and range. The
      elevated PGI-M in smokers (189+/-25, median 174, range 85 to 390 pg/mg
      creatinine) was reduced by rofecoxib to 78+/-27, median 71.5, range 50 to 135
      pg/mg creatinine (P=0.002), and in nonsmokers, PGI-M at baseline (115+/-10,
      median 107, range 67 to 198 pg/mg creatinine) fell to 56+/-15, median 50, range
      34 to 125 pg/mg creatinine (P=0.001) with rofecoxib. The increased excretion of
      Tx-M in smokers (284+/-26, median 252, range 200 to 569 pg/mg creatinine) was
      reduced by 21% to 223+/-16, median 206, range 154 to 383 pg/mg creatinine by
      rofecoxib (P=0.04) but was not changed in nonsmokers. Levels of serum TxB2 were
      not different in smokers and nonsmokers and were unaffected by rofecoxib.
      CONCLUSIONS: The increased prostacyclin biosynthesis in smokers is derived
      largely from the inducible COX-2. COX-2 also contributes to the increased
      biosynthesis of TxA2 in smokers, most likely from inflammatory cells.

PMID- 16087792
TI  - Low-grade albuminuria and incidence of cardiovascular disease events in
      nonhypertensive and nondiabetic individuals: the Framingham Heart Study.
AB  - BACKGROUND: Data are limited with regard to the relations of low-grade
      albuminuria (below the microalbuminuria threshold) and incidence of
      cardiovascular disease (CVD) events in nondiabetic, nonhypertensive individuals.
      METHODS AND RESULTS: We examined the association of urinary albumin excretion
      (spot urine albumin indexed to creatinine [UACR]) and the incidence of CVD events
      and all-cause mortality in 1568 nonhypertensive, nondiabetic Framingham Offspring
      Study participants (mean age, 55 years; 58% women) free of CVD. On follow-up
      (median, 6 years), 54 participants (20 women) developed a first CVD event, and 49
      (19 women) died. After adjustment for established risk factors, increasing UACR
      was associated with greater risk of CVD (hazards ratio [HR] per SD increment in
      log UACR, 1.36; 95% CI, 1.00 to 1.87) and death (HR per SD increment in log UACR,
      1.55; 95% CI, 1.10 to 2.20). Participants with UACR greater than or equal to the
      sex-specific median (> or =3.9 microg/mg for men, > or =7.5 microg/mg for women)
      experienced a nearly 3-fold risk of CVD (adjusted HR, 2.92; 95% CI, 1.57 to 5.44;
      P<0.001) and a borderline significantly increased risk of death (adjusted HR,
      1.75; 95% CI, 0.95 to 3.22; P=0.08) compared with those with UACR below the
      median. The increased CVD risk associated with UACR at or above the median
      remained robust in analyses restricted to individuals without microalbuminuria
      (n=1470) and in subgroups with intermediate (n=1469) and low (n=1186) pretest
      probabilities of CVD. CONCLUSIONS: In our community-based sample of middle-aged
      nonhypertensive, nondiabetic individuals, low levels of urinary albumin excretion
      well below the current microalbuminuria threshold predicted the development of
      CVD. Our observations add to the growing body of evidence that challenges the
      notion that UACR <30 microg/mg indicates "normal" albumin excretion.

PMID- 16087793
TI  - Intrinsic histological abnormalities of aortic root and ascending aorta in
      tetralogy of Fallot: evidence of causative mechanism for aortic dilatation and
      aortopathy.
AB  - BACKGROUND: Dilatation of the aortic root is a known feature in tetralogy of
      Fallot (TOF) patients with pulmonary stenosis (PS) or pulmonary atresia (PA). We
      hypothesized that intrinsic histological abnormalities of the aortic wall present
      since infancy are an important causative factor leading to aortic root
      dilatation. METHODS AND RESULTS: We examined the aortic histology of 17 cases
      with TOF and PS/PA from our cardiac morphology archive and compared them with a
      control group of normal aortas. Measured circumference of the aortic root at the
      sinotubular junction and at the ascending aorta was indexed to the left
      ventricle. Aortic walls were studied by light microscopy with the use of various
      stains. Seventeen TOF cases (7 with PS, 10 with PA) including 7 infants, 2
      children, and 8 adults were compared with 11 hearts with normal aorta. Aortic
      root circumference to left ventricular index and ascending aortic circumference
      to left ventricular index were 1.24+/-0.25 and 1.37+/-0.24, respectively, in the
      TOF group versus 0.89+/-0.10 and 0.88+/-0.11, respectively, in the control group
      (P<0.001). Histological changes of grade 2 or 3 were present in 29%
      (medionecrosis), 82% (fibrosis), 35% (cystic medial necrosis), and 59% (elastic
      fragmentation) in the ascending aorta of the TOF group. Histology grading scores
      were significantly higher in the TOF group (median score, 7; range, 1 to 12)
      compared with normal controls (median score, 2; range, 0 to 6) and correlated
      with the ascending aortic circumference to left ventricular index (r=0.525,
      P=0.03). CONCLUSIONS: There are marked histological abnormalities in the aortic
      root and ascending aortic wall of patients with TOF present from infancy,
      suggesting a causative mechanism for subsequent aortic root dilatation.

PMID- 16087794
TI  - Vascular effects of the human extracellular superoxide dismutase R213G variant.
AB  - BACKGROUND: Extracellular superoxide dismutase (ECSOD) is a major extracellular
      antioxidant enzyme. We have demonstrated that vascular effects of ECSOD require
      an intact heparin-binding domain. A common genetic variant with a substitution in
      the heparin-binding domain (ECSOD(R213G)) was reported recently to be associated
      with ischemic heart disease. The goal of this study was to examine vascular
      effects of ECSOD(R213G). METHODS AND RESULTS: A recombinant adenovirus (Ad) that
      expresses ECSOD(R213G) was constructed. ECSOD(R213G) and ECSOD proteins bound to
      collagen type I in vitro, but binding to aorta ex vivo was 10-fold greater with
      ECSOD than ECSOD(R213G). Three days after intravenous injection of AdECSOD(R213G)
      or AdECSOD in spontaneously hypertensive rats (SHR), immunostaining demonstrated
      binding of ECSOD to carotid arteries and kidneys but minimal binding of
      ECSOD(R213G). Binding to aorta and carotid artery was 2.5- to 3-fold greater with
      ECSOD than ECSOD(R213G) by immunoblotting. Arterial pressure was significantly
      reduced by AdECSOD but not by AdECSOD(R213G). Responses to acetylcholine and
      basal levels of nitric oxide in carotid arteries were impaired in SHR compared
      with normotensive Wistar-Kyoto rats and were improved after AdECSOD but not
      AdECSOD(R213G). Levels of superoxide and nitrotyrosine in aorta were higher in
      SHR than Wistar-Kyoto rats and were greatly reduced after AdECSOD but not
      AdECSOD(R213G). CONCLUSIONS: In contrast to ECSOD, ECSOD(R213G) has no
      significant protective effect on arterial pressure, vascular function, or
      vascular levels of oxidative stress in SHR. These findings may provide a
      mechanistic basis for association studies that suggest that human beings carrying
      ECSOD(R213G) are predisposed to vascular diseases.

PMID- 16087795
TI  - START Trial: a pilot study on STimulation of ARTeriogenesis using subcutaneous
      application of granulocyte-macrophage colony-stimulating factor as a new
      treatment for peripheral vascular disease.
AB  - BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) was
      recently shown to increase collateral flow index in patients with coronary artery
      disease. Experimental models showed beneficial effects of GM-CSF on collateral
      artery growth in the peripheral circulation. Thus, in the present study, we
      evaluated the effects of GM-CSF in patients with peripheral artery disease.
      METHODS AND RESULTS: A double-blinded, randomized, placebo-controlled study was
      performed in 40 patients with moderate or severe intermittent claudication.
      Patients were treated with placebo or subcutaneously applied GM-CSF (10
      microg/kg) for a period of 14 days (total of 7 injections). GM-CSF treatment led
      to a strong increase in total white blood cell count and C-reactive protein.
      Monocyte fraction initially increased but thereafter decreased significantly as
      compared with baseline. Both the placebo group and the treatment group showed a
      significant increase in walking distance at day 14 (placebo: 127+/-67 versus
      184+/-87 meters, P=0.03, GM-CSF: 126+/-66 versus 189+/-141 meters, P=0.04) and at
      day 90. Change in walking time, the primary end point of the study, was not
      different between groups. No change in ankle-brachial index was found on GM-CSF
      treatment at day 14 or at day 90. Laser Doppler flowmetry measurements showed a
      significant decrease in microcirculatory flow reserve in the control group
      (P=0.03) and no change in the GM-CSF group. CONCLUSIONS: The present study does
      not support the use of GM-CSF for treatment of patients with moderate or severe
      intermittent claudication. Issues that need to be addressed are dosing, the
      selection of patients, and potential differences between GM-CSF effects in the
      coronary and the peripheral circulation.

PMID- 16087796
TI  - Bilirubin: a natural inhibitor of vascular smooth muscle cell proliferation.
AB  - BACKGROUND: Bilirubin, a natural product of heme catabolism by heme oxygenases,
      was considered a toxic waste product until 1987, when its antioxidant potential
      was recognized. On the basis of observations that oxidative stress is a potent
      trigger in vascular proliferative responses, that heme oxygenase-1 is
      antiatherogenic, and that several studies now show that individuals with high
      normal or supranormal levels of plasma bilirubin have a lesser incidence of
      atherosclerosis-related diseases, we hypothesized that bilirubin would have
      salutary effects on preventing intimal hyperplasia after balloon injury. METHODS
      AND RESULTS: We found less balloon injury-induced neointima formation in
      hyperbilirubinemic Gunn rats and in wild-type rats treated with biliverdin, the
      precursor of bilirubin, than in controls. In vitro, bilirubin and biliverdin
      inhibited serum-driven smooth muscle cell cycle progression at the G1 phase via
      inhibition of the mitogen-activated protein kinase signal transduction pathways
      and inhibition of phosphorylation of the retinoblastoma tumor suppressor protein.
      CONCLUSIONS: Bilirubin and biliverdin might be potential therapeutics in vascular
      proliferative disorders.

PMID- 16087797
TI  - C-reactive protein, interleukin-6, and soluble adhesion molecules as predictors
      of progressive peripheral atherosclerosis in the general population: Edinburgh
      Artery Study.
AB  - BACKGROUND: The relationship between levels of circulating inflammatory markers
      and risk of progressive atherosclerosis is relatively undetermined. We therefore
      studied inflammatory markers as predictors of peripheral atherosclerotic
      progression, measured by the ankle-brachial index (ABI) at 3 consecutive time
      points over 12 years. METHODS AND RESULTS: The Edinburgh Artery Study is a
      population cohort study of 1592 men and women aged 55 to 74 years. C-reactive
      protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1),
      vascular adhesion molecule-1 (VCAM-1), and E-selectin were measured at baseline.
      Valid ABI measurements were obtained on 1582, 1081, and 813 participants at
      baseline and 5-year and 12-year follow-up examinations, respectively. At
      baseline, a significant trend was found between higher plasma levels of CRP (P<
      or =0.05) and increasing severity of peripheral arterial disease (PAD), after
      adjustment for baseline cardiovascular risk factors. IL-6 at baseline (P< or
      =0.001) was associated with progressive atherosclerosis at 5 years (ABI change
      from baseline), and CRP (P< or =0.01), IL-6 (P< or =0.001), and ICAM-1 (P< or
      =0.01) were associated with changes at 12 years, independently of baseline ABI,
      cardiovascular risk factors, and baseline cardiovascular disease. Only IL-6
      independently predicted ABI change at 5 years (P< or =0.01) and 12 years (P< or
      =0.05) in analyses of all inflammatory markers simultaneously and adjusted for
      baseline ABI, cardiovascular risk factors, and cardiovascular disease at
      baseline. CONCLUSIONS: These findings suggest that CRP, IL-6, and ICAM-1 are
      molecular markers associated with atherosclerosis and its progression. IL-6
      showed more consistent results and stronger independent predictive value than
      other inflammatory markers.

PMID- 16087799
TI  - Discrepancies between catheter tip and tissue temperature in cooled-tip ablation:
      relevance to guiding left atrial ablation.
AB  - BACKGROUND: It is not known whether catheter tip temperatures with a cooled-tip
      ablation can be reliably extrapolated to estimate actual tissue temperatures. The
      relationship between catheter tip temperatures, tissue temperatures, power, and
      microbubble formation is not known. METHODS AND RESULTS: Nine dogs underwent 111
      radiofrequency energy deliveries at the pulmonary vein ostia with a cooled-tip
      catheter. Catheter tip and tissue temperatures were markedly discrepant. Catheter
      tip temperature plateaus at 36 degrees C to 39 degrees C with increasing power,
      whereas tissue temperature increases to a mean of 75+/-3 degrees C at 45 W
      (maximum temperature >100 degrees C). Seventy-two energy deliveries were
      performed, titrating power to microbubble formation guided by intracardiac
      echocardiography. Type I and II microbubble formation occurred in 45 (63%) and 19
      (26%) ablations, respectively. Type I microbubble emergence occurred at lower
      powers (21+/-8 versus 26+/-4 W; P=0.05), catheter tip temperatures (38+/-5
      degrees C versus 48+/-10 degrees C; P=0.02), and tissue temperatures (65+/-19
      degrees C versus 81+/-9 degrees C; P<0.001) than type II microbubble formation.
      Maximum impedance decreases during ablation before microbubble formation were
      less with type I microbubble (20+/-9 versus 37+/-11 Omega; P<0.001) compared with
      type II microbubbles. One quarter of type I microbubbles abruptly transitioned to
      type II microbubbles with significant changes in power or catheter tip
      temperature. No microbubbles were seen in 19 ablations (26%) despite powers up to
      26+/-9 W and tissue temperatures up to 81+/-17 degrees C. CONCLUSIONS: Catheter
      tip and tissue temperatures are markedly discrepant during cooled-tip ablation.
      Type I and II microbubble formation occurs at overlapping power and catheter tip
      and tissue temperature ranges. Neither the absence of microbubbles nor the
      presence of type I microbubble formation ensures against excessive tissue
      heating. The appearance of microbubbles may indicate possible tissue overheating
      and signal a need to decrease energy.

PMID- 16087800
TI  - Real-time three-dimensional echocardiography: a novel technique to quantify
      global left ventricular mechanical dyssynchrony.
AB  - BACKGROUND: Left ventricular (LV) mechanical dyssynchrony (LVMD) has emerged as a
      therapeutic target using cardiac resynchronization therapy (CRT) in selected
      patients with chronic heart failure. Current methods used to evaluate LVMD are
      technically difficult and do not assess LVMD of the whole LV simultaneously. We
      developed and validated real-time 3D echocardiography (RT3DE) as a novel method
      to assess global LVMD. METHODS AND RESULTS: Eighty-nine healthy volunteers and
      174 unselected patients referred for routine echocardiography underwent 2D
      echocardiography and RT3DE. RT3DE data sets provided time-volume analysis for
      global and segmental LV volumes. A systolic dyssynchrony index (SDI) was derived
      from the dispersion of time to minimum regional volume for all 16 LV segments.
      Healthy subjects and patients with normal LV systolic function had highly
      synchronized segmental function (SDI, 3.5+/-1.8% and 4.5+/-2.4%; P=0.7). SDI
      increased with worsening LV systolic function regardless of QRS duration (mild,
      5.4+/-0.83%; moderate, 10.0+/-2%; severe LV dysfunction, 15.6+/-1%; P for trend
      <0.001). We found that 37% of patients with moderate to severe LV systolic
      dysfunction had significant dyssynchrony with normal QRS durations (SDI, 14.7+/
      1.2%). Twenty-six patients underwent CRT. At long-term follow-up, responders
      demonstrated reverse remodeling after CRT with a significant reduction in SDI
      (16.9+/-1.1% to 6.9+/-1%; P<0.0001) and end-diastolic volume (196.6+/-17.3 to
      132.1+/-13.5 mL; P<0.0001) associated with an increase in LV ejection fraction
      (17+/-2.2% to 31.6+/-2.9%; P<0.0001). CONCLUSIONS: RT3DE can quantify global LVMD
      in patients with and without QRS prolongation. RT3DE represents a novel technique
      to identify chronic heart failure patients who may otherwise not be considered
      for CRT.

PMID- 16087801
TI  - Images in cardiovascular medicine. Severe pulmonary artery stenosis caused by
      extrinsic compression of a calcified circular ring.

PMID- 16087802
TI  - Images in cardiovascular medicine. Myocardial infarction caused by occlusion of
      Cabrol conduit graft.

PMID- 16087803
TI  - Images in cardiovascular medicine. Aortic coarctation visualized by 16-row
      detector multislice computed tomography.

PMID- 16087804
TI  - Letter regarding the article by Xue et al, "Functional integration of
      electrically active cardiac derivatives from genetically engineered human
      embryonic stem cells with quiescent recipient ventricular cardiomyocytes".

PMID- 16087805
TI  - Letter regarding the article by Katz et al, "Vascular endothelial dysfunction and
      mortality risk in patients with chronic heart failure".

PMID- 16087806
TI  - Circulating biomarkers in acute coronary syndromes: something different or more
      of the same?

PMID- 16087807
TI  - C-reactive protein and cerebral small-vessel disease: an opportunity to reassess
      small-vessel disease physiopathology?

PMID- 16087808
TI  - Sleep and hypertension: a challenge for the autonomic regulation of the
      cardiovascular system.

PMID- 16087809
TI  - Utility of cardiac magnetic resonance imaging in the diagnosis of hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Two-dimensional echocardiography is currently the standard test for
      the clinical diagnosis of hypertrophic cardiomyopathy (HCM). The present study
      was undertaken to determine whether cardiac MRI (CMR) affords greater accuracy
      than echocardiography in establishing the diagnosis and assessing the magnitude
      of left ventricular (LV) hypertrophy in HCM. METHODS AND RESULTS: Forty-eight
      patients (age 34+/-16 years) suspected of having HCM (or with a confirmed
      diagnosis) were imaged by both echocardiography and CMR to assess LV wall
      thickness in 8 anatomic segments (total n=384 segments) and compared in a blinded
      fashion. Maximum LV thickness was similar by echocardiography (21.7+/-9.1 mm) and
      CMR (22.5+/-9.6 mm; P=0.21). However, in 3 (6%) of the 48 patients,
      echocardiography did not demonstrate LV hypertrophy, and CMR identified otherwise
      undetected areas of wall thickening in the anterolateral LV free wall (17 to 20
      mm), which resulted in a new diagnosis of HCM. In the overall study group,
      compared with CMR, echocardiography also underestimated the magnitude of
      hypertrophy in the basal anterolateral free wall (by 20+/-6%; P=0.001), as well
      as the presence of extreme LV wall thickness (> or =30 mm) in 10% of patients
      (P<0.05). CONCLUSIONS: CMR is capable of identifying regions of LV hypertrophy
      not readily recognized by echocardiography and was solely responsible for
      diagnosis of the HCM phenotype in an important minority of patients. CMR enhances
      the assessment of LV hypertrophy, particularly in the anterolateral LV free wall,
      and represents a powerful supplemental imaging test with distinct diagnostic
      advantages for selected HCM patients.

PMID- 16087810
TI  - High-density lipoprotein deficiency and dyslipoproteinemia associated with venous
      thrombosis in men.
AB  - BACKGROUND: Although dyslipoproteinemia is associated with arterial
      atherothrombosis, little is known about plasma lipoproteins in venous thrombosis
      patients. METHODS AND RESULTS: We determined plasma lipoprotein subclass
      concentrations using nuclear magnetic resonance spectroscopy and antigenic levels
      of apolipoproteins AI and B in blood samples from 49 male venous thrombosis
      patients and matched controls aged <55 years. Venous thrombosis patients had
      significantly lower levels of HDL particles, large HDL particles, HDL
      cholesterol, and apolipoprotein AI and significantly higher levels of LDL
      particles and small LDL particles. The quartile-based odds ratios for decreased
      HDL particle and apolipoprotein AI levels in patients compared with controls were
      6.5 and 6.0 (95% CI, 2.3 to 19 and 2.1 to 17), respectively. Odds ratios for
      apolipoprotein B/apolipoprotein AI ratio and LDL cholesterol/HDL cholesterol
      ratio were 6.3 and 2.7 (95% CI, 1.9 to 21 and 1.1 to 6.5), respectively. When
      polymorphisms in genes for hepatic lipase, endothelial lipase, and cholesteryl
      ester transfer protein were analyzed, patients differed significantly from
      controls in the allelic frequency for the TaqI B1/B2 polymorphism in cholesteryl
      ester transfer protein, consistent with the observed pattern of lower HDL and
      higher LDL. CONCLUSIONS: Venous thrombosis in men aged <55 years old is
      associated with dyslipoproteinemia involving lower levels of HDL particles,
      elevated levels of small LDL particles, and an elevated ratio of apolipoprotein
      B/apolipoprotein AI. This dyslipoproteinemia seems associated with a related
      cholesteryl ester transfer protein genotype difference.

PMID- 16087811
TI  - Does creatinine kinase-MB elevation after percutaneous coronary intervention
      predict outcomes in 2005? Periprocedural cardiac enzyme elevation predicts
      adverse outcomes.

PMID- 16087812
TI  - Effect size estimates of lifestyle and dietary changes on all-cause mortality in
      coronary artery disease patients: a systematic review.
AB  - BACKGROUND: Guidelines for lifestyle and dietary modification in patients with
      coronary artery disease (CAD) are mainly supported by evidence from general
      population studies. CAD patients, however, differ from the general population in
      age (older) and treatment with preventive drugs. This review seeks to provide
      evidence for a prognostic benefit of lifestyle and dietary recommendations from
      studies in CAD patients. METHODS AND RESULTS: A literature search was performed
      on the effect of lifestyle and dietary changes on mortality in CAD patients.
      Prospective cohort studies and randomized controlled trials of patients with
      established CAD were included if they reported all-causes mortality and had at
      least 6 months of follow-up. The effect estimates of smoking cessation (relative
      risk [RR], 0.64; 95% CI, 0.58 to 0.71), increased physical activity (RR, 0.76;
      95% CI, 0.59 to 0.98), and moderate alcohol use (RR, 0.80; 95% CI, 0.78 to 0.83)
      were studied most extensively. For the 6 dietary goals, data were too limited to
      provide reliable effect size estimates. Combinations of dietary changes were
      associated with reduced mortality (RR, 0.56; 95% CI, 0.42 to 0.74). CONCLUSIONS:
      Available studies show convincingly the health benefits of lifestyle changes in
      CAD patients. Effect estimates of combined dietary changes look promising. Future
      studies should confirm these findings and assess the contribution of the
      individual dietary factors.

PMID- 16087813
TI  - Assessing physician compliance with the rules for euthanasia and assisted
      suicide.

PMID- 16087814
TI  - Levothyroxine therapy for hypothyroidism: should we abandon conservative dosage
      titration?

PMID- 16087815
TI  - Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis.
AB  - Oral pseudoephedrine is commonly used to treat symptoms of rhinitis and
      rhinorrhea, but its effect on blood pressure (BP) and heart rate (HR) remains
      uncertain. We assessed whether pseudoephedrine causes clinically meaningful
      elevations in HR or BP. We searched MEDLINE, EMBASE, and the Cochrane Library for
      English-language, randomized placebo-controlled trials of oral pseudoephedrine
      treatment in adults. The primary data extracted were systolic BP (SBP), diastolic
      BP (DBP), and HR. Study quality was assessed using the methods of Jadad, and data
      were synthesized using a random-effects model and weighted mean differences.
      Twenty-four trials had extractable vital sign information (45 treatment arms;
      1285 patients). Pseudoephedrine caused a small but significant increase in SBP
      (0.99, mm Hg; 95% CI, 0.08 to 1.90) and HR (2.83 beats/min; 95% CI, 2.0 to 3.6),
      with no effect on DBP (0.63 mm Hg, 95% CI, -0.10 to 1.35). The effect in patients
      with controlled hypertension demonstrated an SBP increase of similar magnitude
      (1.20 mm Hg; 95% CI, 0.56 to 1.84 mm Hg). Higher doses and immediate-release
      preparations were associated with greater BP increases. Studies with more women
      had less effect on BP or HR. Shorter duration of use was associated with greater
      increases in SBP and DBP.

PMID- 16087816
TI  - Granted, undecided, withdrawn, and refused requests for euthanasia and physician
      assisted suicide.
AB  - BACKGROUND: The aims of this study were to obtain information about the
      characteristics of requests for euthanasia and physician-assisted suicide (EAS)
      and to distinguish among different types of situations that can arise between the
      request and the physician's decision. METHODS: All general practitioners in 18 of
      the 23 Dutch general practitioner districts received a written questionnaire in
      which they were asked to describe the most recent request for EAS they received.
      RESULTS: A total of 3614 general practitioners responded to the questionnaire
      (response rate, 60%). Of all explicit requests for EAS, 44% resulted in EAS. In
      the other cases the patient died before the performance (13%) or finalization of
      the decision making (13%), the patient withdrew the request (13%), or the
      physician refused the request (12%). Patients' most prominent symptoms were
      "feeling bad," "tiredness," and "lack of appetite." The most frequently mentioned
      reasons for requesting EAS were "pointless suffering," "loss of dignity," and
      "weakness." The patients' situation met the official requirements for accepted
      practice best in requests that resulted in EAS and least in refused requests. A
      lesser degree of competence and less unbearable and hopeless suffering had the
      strongest associations with the refusal of a request. CONCLUSIONS: The complexity
      of EAS decision making is reflected in the fact that besides granting and
      refusing a request, 3 other situations could be distinguished. The decisions
      physicians make, the reasons they have for their decisions, and the way they
      arrived at their decisions seem to be based on patient evaluations. Physicians
      report compliance with the official requirements for accepted practice.

PMID- 16087817
TI  - Regional and institutional variation in the initiation of early do-not
      resuscitate orders.
AB  - BACKGROUND: Do-not-resuscitate (DNR) orders are an important step in decision
      making about aggressiveness of care for patients in hospitals. The use of DNR
      orders is known to vary with patient characteristics, but few studies have
      investigated the role of hospital factors or of regional variation. We examined
      these influences on the use of early DNR orders (written <24 hours after
      admission). METHODS: We conducted a retrospective cross-sectional study of
      patients 50 years and older admitted to acute-care hospitals in California in
      2000 from the most prevalent medical and surgical diagnosis related groups. We
      performed multivariate logistic regression predicting use of DNR by hospital
      characteristics while accounting for patient characteristics, and estimated
      indirectly standardized rates of DNR use by county. RESULTS: In the selected
      diagnosis related groups, 819 686 persons were admitted to 386 hospitals. Early
      DNR orders varied from 2% (patients aged 50-59 years) to 17% (patients aged > or
      =80 years). In multivariate analyses, the odds of having early DNR orders written
      were significantly lower in for-profit (vs private nonprofit) hospitals, higher
      in the smallest (vs the largest) hospitals, and lower in academic (vs
      nonacademic) hospitals. Standardized rates of DNR order use varied 10-fold across
      counties. The highest rates were among patients from rural areas. However,
      variation in use did not correspond well to county population, hospital bed
      availability, or population density. CONCLUSIONS: Hospital characteristics appear
      to be associated with the use of DNR orders, even after accounting for
      differences in patient characteristics. This association reflects institutional
      culture, technological bent, and physician practice patterns. If these factors do
      not match patient preferences, then improvements in care are needed.

PMID- 16087818
TI  - The starting dose of levothyroxine in primary hypothyroidism treatment: a
      prospective, randomized, double-blind trial.
AB  - BACKGROUND: The treatment of hypothyroidism with levothyroxine is effective and
      simple; however, recommendations for the starting dose vary considerably. To our
      knowledge, the levothyroxine starting dose has never been studied prospectively.
      METHODS: We conducted a prospective, randomized, double-blind trial that compared
      a full starting levothyroxine dose of 1.6 mug/kg with a low starting dose of 25
      mug (increased every 4 weeks) in patients with newly diagnosed cardiac
      asymptomatic hypothyroidism. Safety was studied by documenting cardiac symptoms
      and events, and efficacy was studied by monitoring thyrotropin and free thyroxine
      levels and by assessing improvement of signs and symptoms and quality of life.
      RESULTS: Seventy-five consecutive patients were enrolled, of whom 50 underwent
      randomization. At baseline, the severity of hypothyroidism and age were
      comparable in the full-dose (n = 25) vs the low-dose group (n = 25): thyrotropin,
      61 vs 48 mIU/L; free thyroxine, 0.56 vs 0.64 ng/dL (7.2 vs 8.2 pmol/L); and age,
      47 vs 47 years. No cardiac complaints or events were documented during treatment
      or at bicycle ergometry at baseline, 12 weeks, or 24 weeks. Euthyroidism was
      reached in the full-dose vs the low-dose group in 13 vs 1 (4 weeks), 19 vs 3 (8
      weeks), 19 vs 9 (12 weeks), 20 vs 14 (16 weeks), 20 vs 18 (20 weeks), and 21 vs
      20 (24 weeks) patients (P = .005). However, signs and symptoms of hypothyroidism
      and quality of life improved at a comparable rate. CONCLUSION: A full starting
      dose of levothyroxine in cardiac asymptomatic patients with primary
      hypothyroidism is safe and may be more convenient and cost-effective than a low
      starting dose regimen.

PMID- 16087819
TI  - Improving processes of hospital care during the last hours of life.
AB  - BACKGROUND: Known for excellence in care in the last days and hours of life,
      hospice programs can help individuals have a "good death" and lead to higher
      family satisfaction with quality of care. Our objective was to evaluate the
      effectiveness of a multicomponent palliative care intervention based on the best
      practices of home hospice and designed to improve the quality of care provided
      for patients dying in an acute care inpatient setting. METHODS: This study was a
      before-after intervention trial conducted between 2001 and 2003. Participants
      included physician, nursing, and ancillary staff on inpatient services of an
      urban, tertiary care Veterans Affairs medical center. The palliative care
      intervention included staff education and support to identify patients who were
      actively dying and implement care plans guided by a comfort care order set
      template for the last days or hours of life. Data abstracted from computerized
      medical records of 203 veterans who died during a 6-month period before (n = 108)
      and after (n = 95) intervention were used to determine the impact of intervention
      on symptom documentation and 5 process of care indicators. RESULTS: There was a
      significant increase in the mean (SD) number of symptoms documented from 1.7
      (2.1) to 4.4 (2.7) (P<.001), and the number of care plans increased from 0.4
      (0.9) to 2.7 (2.3) (P<.001). Opioid medication availability increased from 57.1%
      to 83.2% (P<.001), and do-not-resuscitate orders increased from 61.9% to 85.1%
      (P<.001). There were nonsignificant changes in the proportion of deaths that
      occurred in intensive care units (P = .17) and in the use of nasogastric tubes (P
      = .40), and there was a significant increase in the use of restraints (P<.001).
      CONCLUSION: Our results indicate that end-of-life care improved after the
      introduction of the palliative care program.

PMID- 16087820
TI  - Discomfort in nursing home patients with severe dementia in whom artificial
      nutrition and hydration is forgone.
AB  - BACKGROUND: While there is debate about whether it may be better to forgo than to
      initiate artificial nutrition and hydration (ANH) in nursing home patients with
      severe dementia, the consequences of forgoing ANH in these patients, in
      particular their discomfort, have not yet been investigated. METHODS: In this
      prospective, longitudinal, observational study of 178 patients in Dutch nursing
      homes, discomfort was measured at all measurement times according to the
      observational Discomfort Scale-Dementia of Alzheimer Type. Furthermore, at all
      measurement times, plausible determinants of discomfort were registered. Data
      were analyzed with the statistical technique of generalized estimated equations.
      RESULTS: Decisions to forgo ANH were made most often in severely demented, female
      patients with an acute illness as the most important diagnosis at that time. The
      mean level of discomfort was highest at the time of the decision and decreased in
      the days thereafter. There were substantial differences in level of discomfort
      between patients. Dyspnea, restlessness, and physicians' observations of pain and
      dehydration were associated with higher levels of discomfort. Furthermore,
      patients who were awake had higher levels of observed discomfort than patients
      who were asleep. CONCLUSIONS: Forgoing ANH in patients with severe dementia who
      scarcely or no longer eat or drink seems, in general, not to be associated with
      high levels of discomfort. The individual differences emphasize the need for
      constant attention for possible discomfort.

PMID- 16087821
TI  - The prevention of hip fracture with risedronate and ergocalciferol plus calcium
      supplementation in elderly women with Alzheimer disease: a randomized controlled
      trial.
AB  - BACKGROUND: A high incidence of fractures, particularly of the hip, represents an
      important problem in patients with Alzheimer disease (AD), who are prone to falls
      and have osteoporosis. We previously found that deficiency of 25-hydroxyvitamin D
      and compensatory hyperparathyroidism cause reduced bone mineral density in female
      patients with AD. We address the possibility that treatment with risedronate
      sodium and ergocalciferol plus calcium supplementation may reduce the incidence
      of nonvertebral fractures in elderly women with AD. METHODS: A total of 500
      elderly women with AD were randomly assigned to daily treatment with 2.5 mg of
      risedronate sodium or a placebo, combined with 1000 IU of ergocalciferol and 1200
      mg of elementary calcium, and followed up for 18 months. RESULTS: At baseline,
      patients of both groups showed 25-hydroxyvitamin D deficiency with compensatory
      hyperparathyroidism. During the study period, bone mineral density in the
      risedronate group increased by 4.1% and decreased by 0.9% in the control group.
      Vertebral fractures occurred in 29 patients (24 hip fractures) in the control
      group and 8 patients (5 hip fractures) in the risedronate group. The relative
      risk in the risedronate group compared with the control group was 0.28 (95%
      confidence interval, 0.13-0.59). CONCLUSIONS: Elderly patients with AD
      hypovitaminosis D are at increased risk for hip fracture. Treatment with
      risedronate and ergocalciferol may be safe and effective in reducing the risk of
      a fracture in elderly patients with AD.

PMID- 16087822
TI  - Risedronate sodium therapy for prevention of hip fracture in men 65 years or
      older after stroke.
AB  - BACKGROUND: There is a high incidence of hip fractures in patients after
      hemiplegic stroke. Bone mineral density is decreased on the hemiplegic side in
      patients after stroke, correlating with the immobilization-induced bone
      resorption, the degree of paralysis, and hypovitaminosis D. The purpose of this
      study is to evaluate the effectiveness of risedronate sodium, an inhibitor of
      bone resorption, on osteoporosis and the risk of hip fractures in men 65 years or
      older after stroke. METHODS: We conducted an 18-month randomized double-blind
      trial. Of 280 male patients 65 years or older who were poststroke, 140 received a
      daily dose of 2.5 mg risedronate sodium and the other 140 received placebo.
      Incidence of hip fractures in the 2 groups was compared. RESULTS: Ten patients
      sustained hip fractures in the placebo group, and 2 hip fractures occurred in the
      risedronate group. The relative risk of a hip fracture was 0.19 (95% confidence
      interval, 0.04-0.89). The number of patients needing the treatment was 16 (95%
      confidence interval, 9-32). Bone mineral density increased by 2.5% in the
      risedronate group and decreased by 3.5% in the placebo group (P<.001). Urinary
      deoxypyridinoline, a bone resorption marker, decreased by 58.7% in the
      risedronate group and by 37.2% in the placebo group. CONCLUSION: Treatment with
      risedronate increases bone mineral density and reduces hip fractures in elderly
      men who are poststroke.

PMID- 16087823
TI  - The role of patient-physician trust in moderating medication nonadherence due to
      cost pressures.
AB  - BACKGROUND: Prescription drug costs constitute a burden for many chronically ill
      adults and are strongly related to patients' likelihood of using less medication
      than prescribed. We examined the extent to which patients' trust in their
      physicians may moderate the impact of economic constraints and other risk factors
      for cost-related adherence problems. METHODS: A total of 912 patients with
      diabetes recruited from 5 Veterans Affairs health systems completed a detailed
      cross-sectional survey. Patients reported their level of physician trust using a
      standard scale and were stratified into high-trust (n = 557) and low-trust (n =
      355) groups. We fit multivariate logistic regression models with terms
      characterizing the interactions between physician trust and (1) patients' out-of
      pocket medication costs and (2) patients' income, as well as other possible risk
      factors for cost-related underuse. RESULTS: Patients with higher out-of-pocket
      costs were more likely to forgo medications because of cost pressures when
      physician trust levels were low. Having a low income was only associated with
      cost-related adherence problems in the context of low physician trust. Patients
      who reported medication underuse for reasons other than cost were 4 times as
      likely as other patients to also report cost-related underuse, and those with
      significant depressive symptoms had more than twice the risk of cost-related
      underuse compared with those without depression (both P<.05). CONCLUSIONS: These
      findings suggest that a trusting physician relationship may moderate the impact
      of cost pressures on patients' medication adherence. More generally, addressing
      noncost barriers to adherence may reduce rates of cost-related medication
      underuse.

PMID- 16087824
TI  - The burden of Staphylococcus aureus infections on hospitals in the United States:
      an analysis of the 2000 and 2001 Nationwide Inpatient Sample Database.
AB  - BACKGROUND: Previous studies have investigated the impact of Staphylococcus
      aureus infections on individual hospitals, but to date, no study using nationally
      representative data has estimated this burden. METHODS: This is a retrospective
      analysis of the 2000 and 2001 editions of the Agency for Healthcare Research and
      Quality's Nationwide Inpatient Sample database, which represents a stratified 20%
      sample of hospitals in the United States. All inpatient discharge data from 994
      hospitals in 28 states during 2000 and from 986 hospitals in 33 states during
      2001, representing approximately 14 million inpatient stays, were analyzed to
      determine the association of S aureus infections with length of stay, total
      charges, and in-hospital mortality. RESULTS: Staphylococcus aureus infection was
      reported as a discharge diagnosis for 0.8% of all hospital inpatients, or 292 045
      stays per year. Inpatients with S aureus infection had, on average, 3 times the
      length of hospital stay (14.3 vs 4.5 days; P<.001), 3 times the total charges
      (48,824 US dollars vs 14,141 US dollars; P<.001), and 5 times the risk of in
      hospital death (11.2% vs 2.3%; P<.001) than inpatients without this infection.
      Even when controlling for hospital fixed effects and for patient differences in
      diagnosis-related groups, age, sex, race, and comorbidities, the differences in
      mean length of stay, total charges, and mortality were significantly higher for
      hospitalizations associated with S aureus. CONCLUSIONS: Staphylococcus aureus
      infections represent a considerable burden to US hospitals, particularly among
      high-risk patient populations. The potential benefits to hospitals in terms of
      reduced use of resources and costs as well as improved outcomes from preventing S
      aureus infections are significant.

PMID- 16087825
TI  - Opposite bone remodeling effects of teriparatide and alendronate in increasing
      bone mass.
AB  - BACKGROUND: Antiresorptive agents for the treatment of osteoporosis suppress bone
      remodeling and reestablish bone turnover at a lower rate to reduce bone loss.
      Recombinant teriparatide (human parathyroid hormone 1-34) stimulates bone
      formation, increases bone mass, and improves bone microarchitecture. We
      contrasted the effects of once-daily doses of 20 mug of teriparatide and 10 mg of
      alendronate sodium on bone mineral density (BMD) and markers of bone turnover.
      METHODS: Markers of bone turnover and areal BMD were assessed in 203
      postmenopausal women with osteoporosis in an 18-month randomized parallel double
      blind study; volumetric BMD was measured in a subset of women. RESULTS:
      Teriparatide significantly increased markers of bone turnover that peaked at 6
      months (serum procollagen type I N-terminal propeptide, 218%, and urinary N
      telopeptide corrected for creatinine, 58%; P<.001); alendronate significantly
      decreased the markers at 6 months (-67% and -72%, respectively; P<.001). At 18
      months, areal and volumetric spine BMDs were significantly higher with
      teriparatide than with alendronate (10.3% vs 5.5% [P<.001] and 19.0% vs 3.8%
      [P<.01], respectively). Areal femoral neck BMD was significantly higher than
      baseline in the teriparatide and alendronate groups (3.9% and 3.5%,
      respectively). There were no significant differences in trabecular femoral neck
      BMD between the teriparatide and alendronate groups (4.9% and 2.2%,
      respectively). Cortical volumetric femoral neck BMD was significantly different
      between the teriparatide and alendronate groups (-1.2% and 7.7%, respectively; P
      = .05). CONCLUSION: Two distinct options for the management of osteoporosis lead
      to increases in BMD by opposite mechanisms of action on bone remodeling.

PMID- 16087826
TI  - Barriers and facilitators to primary care or human immunodeficiency virus clinics
      providing methadone or buprenorphine for the management of opioid dependence.
AB  - BACKGROUND: Federal initiatives aim to increase office-based treatment of opioid
      dependence, but, to our knowledge, factors associated with willingness to deliver
      this care have not been defined. The objective of this study was to describe
      clinics' willingness to provide methadone hydrochloride or buprenorphine
      hydrochloride for opioid dependence. METHODS: The design of the study was a
      survey conducted in New York State. Two hundred sixty-one directors of primary
      care and/or human immunodeficiency virus specialty clinics (response rate, 61.1%)
      that serve Medicaid enrollees were questioned. Outcomes were willingness to
      provide methadone and buprenorphine. Predictors included clinic characteristics,
      attitudes about drug users and their treatment, and reported barriers and
      facilitators to treatment. RESULTS: Clinics were more willing to provide
      buprenorphine than methadone treatment (59.8% vs 32.6%; P < .001). Clinics
      offering human immunodeficiency virus specialty care (adjusted odds ratio [AOR],
      2.16; 95% confidence interval [CI], 1.18-3.95) or a safe location to store
      narcotics (AOR, 2.99; 95% CI, 1.57-5.70) were more willing to prescribe
      buprenorphine and more willing to provide methadone. Willingness was positively
      associated with continuing medical education credits for training, but negatively
      associated with greater concern about medication abuse. Immediate telephone
      access to an addiction expert was associated with willingness to provide
      buprenorphine (AOR, 2.08; 95% CI, 1.15-3.76). Greater willingness to provide
      methadone was associated with a belief that methadone-treated patients should be
      seen along with other patients (AOR, 6.20; 95% CI, 1.78-21.64), methadone program
      affiliation (AOR, 4.76; 95% CI, 1.64-13.82), and having more patients with
      chronic pain in the clinic (AOR, 2.80; 95% CI, 1.44-5.44). CONCLUSIONS: These
      clinics serving Medicaid enrollees were more receptive to buprenorphine than
      methadone treatment. Willingness to provide this care was greater in clinics
      offering human immunodeficiency virus services, treating more chronic pain, or
      affiliated with methadone programs. Accessible addiction experts and continuing
      medical education for training may facilitate adoption of this care.

PMID- 16087827
TI  - Prognostic role of echocardiography among patients with acute pulmonary embolism
      and a systolic arterial pressure of 90 mm Hg or higher.
AB  - BACKGROUND: The prognostic role of echocardiographic right ventricular (RV)
      dysfunction for predicting mortality in patients with acute pulmonary embolism
      and a preserved systemic arterial pressure remains controversial. METHODS: We
      evaluated 1035 patients with pulmonary embolism from the International
      Cooperative Pulmonary Embolism Registry who (1) presented with systolic systemic
      arterial pressure of 90 mm Hg or higher and (2) who underwent echocardiography
      within 24 hours of a diagnosis of pulmonary embolism, showing presence (n = 405)
      or absence (n = 630) of RV hypokinesis. The main outcome measure was the
      cumulative survival rate through 30 days in patients with and without RV
      hypokinesis. RESULTS: In patients with RV hypokinesis, the initial systolic
      systemic pressure was lower (125 +/- 22 mm Hg vs 131 +/- 22 mm Hg; P<.001), and
      the initial heart rate was higher (104 +/- 21 beats per minute vs 99 +/- 22 beats
      per minute; P<.001) than in patients without RV hypokinesis. Cancer was less
      often present (14.1% vs 22.5%, P = .001). The 30-day survival rates in patients
      with and without RV hypokinesis were 83.7% (95% confidence interval [CI], 79.3%
      87.0%) and 90.6% (95% CI, 88.0%-92.6%), respectively (log-rank P value <.001).
      The univariate hazard ratio of RV hypokinesis for predicting 30-day mortality was
      2.11 (95% CI, 1.41-3.16; P<.001). Right ventricular hypokinesis remained an
      independent predictor of 30-day mortality (hazard ratio, 1.94; 95% CI, 1.23-3.06)
      after adjusting for univariately significant predictors, including cancer,
      congestive heart failure, chronic lung disease, age older than 70 years, systolic
      arterial pressure of 100 mm Hg or lower, administration of thrombolytic therapy,
      and heart rate greater than 100 beats per minutes. CONCLUSION: Among patients
      with pulmonary embolism who present with a systolic arterial pressure greater
      than or equal to 90 mm Hg, echocardiographic RV hypokinesis is an independent
      predictor of early death.

PMID- 16087828
TI  - Incidence of venous thromboembolism in the year before the diagnosis of cancer in
      528,693 adults.
AB  - BACKGROUND: It is unclear how frequently unprovoked venous thromboembolism (VTE)
      reflects the presence of an occult cancer. METHODS: The California Cancer
      Registry was used to identify diagnosed cases of 19 common malignancies during a
      6-year period. Cases were linked to a hospital discharge database to identify
      incident VTE events in the year before the cancer diagnosis date. The
      standardized incidence ratio (SIR) of unprovoked VTE was determined by using the
      age-, race-, and sex-specific incidence rates in California. RESULTS: Among
      528,693 cancer cases, 596 (0.11%) were associated with a diagnosis of unprovoked
      VTE within 1 year of the cancer diagnosis, compared with 443.0 expected cases
      (SIR, 1.3; 95% confidence interval, 1.2-1.5; P<.001). Among cases with metastatic
      stage cancer, the SIR was 2.3 (95% confidence interval, 2.0-2.6; P<.001), whereas
      for all other stages, the SIR was 1.07 (95% confidence interval, 0.97-1.18; P =
      .09). The incidence of preceding VTE was increased over that expected only during
      the 4-month period immediately preceding the cancer diagnosis date (P<.001). Only
      7 cancer types were associated with a significantly elevated SIR: acute
      myelogenous leukemia; non-Hodgkin lymphoma; and renal cell, ovarian, pancreatic,
      stomach, and lung cancer (SIR range, 1.8-4.2). CONCLUSIONS: In the year preceding
      the diagnosis of cancer, the number of cases with unprovoked VTE was modestly
      higher than expected, and almost all of the unexpected VTE cases were associated
      with a diagnosis of metastatic-stage cancer within 4 months. Given the timing and
      advanced stage of the unexpected cases, it is unlikely that earlier diagnosis of
      these cancers would have significantly improved long-term survival.

PMID- 16087829
TI  - Left atrium size and the risk of cardiovascular death in middle-aged men.
AB  - BACKGROUND: The echocardiographic identification of subclinical risk markers may
      enhance risk stratification for the development of cardiovascular outcomes in the
      general population. Although echocardiography is widely used in the evaluation of
      cardiac structures and function, the prognostic value of echocardiographic
      assessment of left atrium (LA) size for risk stratification of cardiovascular
      death is unknown. METHODS: Left ventricular (LV) mass and LA size were measured
      by using M-mode echocardiography in a representative population-based sample of
      830 men (age, 42-61 years) from eastern Finland. There were 54 deaths due to
      cardiovascular disease during an average follow-up of 13 years. RESULTS: The
      strongest risk factors for cardiovascular death were smoking, family history of
      coronary heart disease, low exercise capacity, elevated blood pressure, exercise
      induced myocardial ischemia, and large LA diameter. Men in the highest tertile of
      LA diameter (>43 mm) had a 2.3-fold (95% confidence interval, 1.1-5.0) risk of
      cardiovascular death compared with men in the lowest tertile of LA diameter (<39
      mm), after adjusting for other risk factors and the use of antihypertensive
      medications. The excess risk for cardiovascular mortality appeared to reside
      largely in the highest tertile of LA size. After additional adjustment for LV
      mass, the relation between LA size and mortality did not remain statistically
      significant (relative risk, 1.5; 95% confidence interval, 0.8-4.1; P = .15) in
      this group. CONCLUSIONS: This prospective population-based study shows that
      echocardiographically defined LA diameter was directly related to the risk of
      cardiovascular death. The association of LA enlargement to cardiovascular death
      appears to be partially related to LV hypertrophy.

PMID- 16087830
TI  - A prediction model for isolating inpatients with suspected pulmonary
      tuberculosis.

PMID- 16087831
TI  - Additional information can enhance validation of tuberculosis isolation
      prediction model.

PMID- 16087832
TI  - Leukocyte response to dental plaque accumulation: a risk factor for heart
      disease?

PMID- 16087833
TI  - Underlying chronic infection and leukocyte count.

PMID- 16087834
TI  - Can the obesity paradox be explained by the protective effects of peripheral
      adiposity?

PMID- 16087835
TI  - Obesity paradox as a component of reverse epidemiology in heart failure.

PMID- 16087836
TI  - A randomized controlled trial to determine the effectiveness of prism spectacles
      for patients with age-related macular degeneration.
AB  - OBJECTIVE: To determine the effectiveness of prism spectacles in people with age
      related macular degeneration by relocating the retinal image. METHODS: We
      implemented a randomized, placebo-controlled, double-masked trial. Participants
      with age-related macular degeneration received a standard low-vision assessment
      and the prescription of conventional low-vision aids 6 weeks before the study
      intervention. Participants were randomized to receive 1 of the following,
      including the optimal refractive correction: (1) custom, incorporating bilateral
      prisms to match participants' preferred power and base direction; (2) standard,
      incorporating standard bilateral prisms (6 prism diopters [Delta] base up for
      logMAR [logarithm of the minimum angle of resolution] visual acuity (VA) of 0.48
      1.00 and 10Delta base up for logMAR VA of 1.02-1.68); or (3) placebo, consisting
      of spectacles matched in weight and thickness to prism spectacles but without
      prism. MAIN OUTCOME MEASURES: Outcomes measured binocularly at baseline and 3
      month follow-up included distance logMAR VA, reading speed, critical print size,
      visual functioning questionnaires, and observed visual task performance. Scores
      on the 25-item National Eye Institute Visual Functioning Questionnaire and the
      Melbourne Low-Vision ADL (Activities of Daily Living) Index were converted to
      linear estimates using Rasch analysis. The Manchester Low Vision Questionnaire
      was used to collect descriptive data. RESULTS: A total of 225 participants
      completed the trial (median age, 81 years). We found no significant effect of
      treatment group on any of the outcome measures, including VA, the primary outcome
      (adjusted for baseline) (P = .63). Participants' responses to the Manchester Low
      Vision Questionnaire suggested that the prism spectacles added to their problems.
      CONCLUSIONS: Prism spectacles are no more effective than conventional spectacles
      for people with age-related macular degeneration.

PMID- 16087837
TI  - Comparison of optical coherence tomography and ultrasound biomicroscopy for
      detection of narrow anterior chamber angles.
AB  - OBJECTIVE: To assess the accuracy of classification of narrow anterior chamber
      (AC) angles using quantitative imaging by optical coherence tomography (OCT) and
      ultrasound biomicroscopy (UBM). DESIGN: Observational comparative study. METHODS:
      A high-speed (4000 axial scans/s) anterior segment OCT prototype was developed
      using a 1.3-microm light source. Seventeen normal subjects (17 eyes) and 7
      subjects (14 eyes) with narrow angle glaucoma were enrolled. All subjects
      underwent gonioscopy, OCT, and UBM. Quantitative AC angle parameters (angle
      opening distance, angle recess area, and the trabecular-iris space area [a new
      parameter we have defined]) were measured from OCT and UBM images using
      proprietary processing software. MAIN OUTCOME MEASURES: Specificity and
      sensitivity in identifying narrow angles with image-derived AC angle parameters.
      RESULTS: Eight of 31 eyes were classified as having narrow angles (Shaffer grade
      < or =1 in all quadrants). The AC angle parameters measured by both OCT and UBM
      had similar mean values, reproducibility, and sensitivity-specificity profiles.
      Both OCT and UBM showed excellent performance in identifying eyes with narrow
      angles. Areas under the receiver operating characteristic curves for these
      parameters were all in the range of 0.96 to 0.98. CONCLUSIONS: Optical coherence
      tomography was similar to UBM in quantitative AC angle measurement and detection
      of narrow angles. In addition, it was easier to use and did not require contact
      with the eye. Optical coherence tomography is a promising method for screening
      individuals at risk for narrow angle glaucoma.

PMID- 16087838
TI  - Pupil ovalization after phakic intraocular lens implantation is associated with
      sectorial iris hypoperfusion.
AB  - OBJECTIVE: To investigate iris perfusion in patients with and without pupil
      ovalization after phakic intraocular lens implantation. METHODS: Comparative
      retrospective randomized case series of 6 participants, each with a regular
      pupil, and 6 participants with pupil ovalization after phakic intraocular lens
      implantation for high myopia were included in the study. Indocyanine green
      angiography was performed between 20 and 40 months (mean +/- SD, 26 +/- 6.1
      months) after lens implantation. RESULTS: Iris perfusion defects were found in 5
      of 6 patients with pupil ovalization. No perfusion deficits were noted in
      patients with round pupils. CONCLUSION: Iris ovalization after phakic intraocular
      lens implantation may be associated with a lack of iris perfusion and with
      secondary ischemia. Patients with these lenses and pupil ovalization should be
      followed regularly.

PMID- 16087839
TI  - Changes in multifocal electroretinograms induced by transpupillary thermotherapy.
AB  - OBJECTIVE: To determine retinal function after transpupillary thermotherapy (TTT)
      for subfoveal choroidal neovascularization using multifocal electroretinograms
      (mfERGs). METHODS: Multifocal electroretinograms were recorded before and after
      TTT (wavelength, 810 nm; diameter, 3 mm; duration, 60 seconds; power, 350 mW) in
      9 eyes in 9 patients with subfoveal choroidal neovascularizations. The stimulus
      consisted of 7 hexagons; the central hexagon covered the laser-irradiated area
      and the surrounding 6 hexagons covered the nonirradiated area. Each recording was
      completed within 1 minute, and mfERGs were recorded periodically during the first
      60 minutes after TTT and also at 24 hours and 1 week after TTT. RESULTS: The
      amplitude of mfERGs from irradiated areas was significantly reduced at 1 minute
      after TTT (P< .01) and then recovered soon. The peak time was prolonged at 15
      minutes after TTT (P< .01), recovered to pre-TTT levels at 60 minutes, and then
      was prolonged again at 24 hours (P< .05) and 1 week (P< .05) after TTT. The
      mfERGs in nonirradiated areas were unchanged during the observational period.
      CONCLUSIONS: We found amplitude reduction in central focal ERGs at 1 minute after
      TTT, transient peak-time delay at 15 minutes, and a delay at 24 hours. Early
      reduction is probably directly caused by an increase in temperature during TTT as
      previously reported in focal flicker ERGs. Peak-time delays at 15 minutes and 24
      hours may be caused by other factors, such as increased intracellular calcium
      (Ca(2+)), the release of nitric oxide or heat shock proteins, vasodilation, or
      change in choroidal neovascularization. Our findings indicate that recording
      mfERGs may be a useful tool for evaluating TTT procedures.

PMID- 16087840
TI  - Acute endophthalmitis incidence: intravitreal triamcinolone.
AB  - OBJECTIVE: To report the incidence of acute postinjection endophthalmitis
      following intravitreal injection of triamcinolone acetonide (IVTA) as an office
      procedure. METHODS: Retrospective, noncomparative, consecutive, interventional
      case series of all patients who had received IVTA at 2 clinical centers between
      January 1, 2000, and January 30, 2004. RESULTS: A total of 1006 eyes received
      IVTA. None of the eyes developed acute, culture-positive, postoperative
      endophthalmitis in the 6 weeks following the procedure. One patient developed
      acute, culture-negative, postoperative endophthalmitis 4 days after receiving
      IVTA, resulting in an incidence of 0.10%. In this case, the presenting symptoms
      were decreased vision and acute conjunctival erythema. The case was notable for
      the absence of pain or hypopyon. CONCLUSION: Although acute postoperative
      endophthalmitis may follow IVTA, our experience suggests that this is a
      relatively uncommon event.

PMID- 16087841
TI  - Management of inferior breaks in pseudophakic rhegmatogenous retinal detachment
      with pars plana vitrectomy and air.
AB  - OBJECTIVE: To determine the role of pars plana vitrectomy without scleral
      buckling and air as a tamponade with 24 hours of prone positioning in the
      management of inferior breaks in primary pseudophakic rhegmatogenous retinal
      detachment. METHODS: Prospective, noncomparative, interventional case series.
      Fifteen consecutive eyes (15 patients) with primary pseudophakic rhegmatogenous
      retinal detachment with causative breaks located between the 4-o'clock and 8
      o'clock positions underwent pars plana vitrectomy with air tamponade. The prone
      position was maintained for 24 hours. Anatomic and functional results are
      presented. RESULTS: The anatomic reattachment rate was 93.3% after 1 procedure
      and 100% at the 6-month visit. Mean preoperative best-corrected visual acuity was
      20/60 (range, 20/400 to 20/25) and mean postoperative best-corrected visual
      acuity was 20/30 (range, 20/100 to 20/20). In 1 case the retina redetached at the
      second week because of an undetected break. Postoperative epiretinal membrane was
      observed in 1 case. CONCLUSION: Pars plana vitrectomy and air tamponade with only
      24 hours of prone positioning postoperatively is effective in the management of
      primary pseudophakic rhegmatogenous retinal detachment with causative breaks
      between the 4-o'clock and 8-o'clock positions.

PMID- 16087842
TI  - The reversed fixation test: a diagnostic test for dissociated horizontal
      deviation.
AB  - BACKGROUND: Dissociated horizontal deviation is one of several conditions that
      manifest unequal horizontal deviations depending on which of the 2 eyes is
      fixating. PURPOSE: To describe the reversed fixation test as an essential tool to
      establish the diagnosis of dissociated horizontal deviation. METHODS: Analysis of
      4 case scenarios depicting the utility of the reversed fixation test. RESULTS:
      The reversed fixation test distinguishes dissociated horizontal deviation from an
      unequal exodeviation of the 2 eyes resulting from postoperative slippage or
      weakness of a horizontal rectus muscle. CONCLUSION: The reversed fixation test is
      necessary to establish the diagnosis of dissociated horizontal deviation.

PMID- 16087843
TI  - Spontaneous uveal amelanotic melanoma in transgenic Tyr-RAS+ Ink4a/Arf-/- mice.
AB  - OBJECTIVE: To characterize a murine model of spontaneous amelanotic melanoma
      arising in the uvea of transgenic mice bearing a targeted deletion of the
      Ink4a/Arf tumor suppressor locus (exons 2 and 3) and expressing human H-ras
      controlled by the human tyrosinase promoter. METHODS: Ocular lesions developed in
      20 (15.7%) of 127 male albino Tyr-RAS+ Ink4a/Arf-/- transgenic FVB/N mice within
      6 months, and were evaluated histologically and ultrastructurally. RESULTS: Uveal
      melanomas were locally invasive but confined to the eye, with no evidence of
      metastasis. Tumor cells exhibited epithelioid and spindle-shaped morphological
      features and closely resembled the human counterpart. Melan-A, S100 and neuron
      specific enolase expression were detected immunohistochemically. Melanosomal
      structures were detected using electron microscopy. The retinal pigment
      epithelium was intact above small melanomas, and electron microscopy of the
      tumors failed to show the presence of basement membrane formation or desmosomes.
      CONCLUSION: Spontaneous uveal malignant melanomas occurring in male Tyr-RAS+
      Ink4a/Arf-/- transgenic mice arise within the choroid or ciliary body and share
      histopathological features characteristic of human uveal melanoma. CLINICAL
      RELEVANCE: Uveal melanoma research has benefited from xenograft models, but
      engineered mouse models of spontaneous uveal amelanotic melanoma will undoubtedly
      further our understanding of the genetic underpinning for this disease.

PMID- 16087844
TI  - Fundus and histopathological study of radial optic neurotomy in the normal
      miniature pig eye.
AB  - OBJECTIVE: To demonstrate the fundus and histopathological changes in the normal
      miniature pig eye after radial optic neurotomy. METHODS: Ophthalmoscopic
      examinations, fundus photography, and fluorescein angiography were performed on
      12 eyes that underwent radial optic neurotomy, 5 normal eyes, and 7 eyes that
      underwent vitrectomy (from 12 pigs in total) preoperatively and 1, 7, 14, 30, and
      90 days postoperatively. These eyes were enucleated 120 days postoperatively.
      Sixteen eyes (of 8 pigs in total) that underwent radial optic neurotomy were
      enucleated 1, 3, 7, and 48 days (2 pigs each time) postoperatively. The
      enucleated eye sections were stained with hematoxylin-eosin, Masson trichrome,
      and Luxol fast blue. RESULTS: The retina radial to the site of radial optic
      neurotomy darkened gradually with the increasing curvature of the major retinal
      arteries. The filling time intervals from the retinal artery to the retinal vein
      were prolonged. At the incision site, there was a loss of nerve fibers, which
      were subsequently replaced by collagenous tissue. No anastomotic vessels formed
      by the end of the study. CONCLUSIONS: Postoperatively, the retinal circulation
      seemed somewhat sluggish compared with that seen preoperatively. Segmental
      retinal nerve atrophy eventually formed. The procedure itself may not be the sole
      factor for the formation of shunt vessels. CLINICAL RELEVANCE: To date, radial
      optic neurotomy is controversial and persuasive animal studies are lacking. In
      combining fluorescein angiography with histopathological examination, this study
      may be somewhat helpful.

PMID- 16087845
TI  - Cosmic radiation increases the risk of nuclear cataract in airline pilots: a
      population-based case-control study.
AB  - BACKGROUND: Aviation involves exposure to ionizing radiation of cosmic origin.
      The association between lesions of the ocular lens and ionizing radiation is well
      known. OBJECTIVE: To investigate whether employment as a commercial airline pilot
      and the resulting exposure to cosmic radiation is associated with lens
      opacification. METHODS: This is a population-based case-control study of 445 men.
      Lens opacification was classified into 4 types using the World Health
      Organization simplified grading system. These 4 types, serving as cases, included
      71 persons with nuclear cataracts, 102 with cortical lens opacification, 69 with
      central optical zone involvement, and 32 with posterior subcapsular lens
      opacification. Control subjects are those with a different type of lens
      opacification or without lens opacification. Exposure was assessed based on
      employment time as pilots, annual number of hours flown on each aircraft type,
      time tables, flight profiles, and individual cumulative radiation doses (in
      millisieverts) calculated by a software program. Odds ratios were calculated
      using logistic regression. RESULTS: The odds ratio for nuclear cataract risk
      among cases and controls was 3.02 (95% confidence interval, 1.44-6.35) for pilots
      compared with nonpilots, adjusted for age, smoking status, and sunbathing habits.
      The odds ratio for nuclear cataract associated with estimation of cumulative
      radiation dose (in millisieverts) to the age of 40 years was 1.06 (95% confidence
      interval, 1.02-1.10), adjusted for age, smoking status, and sunbathing habits.
      CONCLUSION: The association between the cosmic radiation exposure of pilots and
      the risk of nuclear cataracts, adjusted for age, smoking status, and sunbathing
      habits, indicates that cosmic radiation may be a causative factor in nuclear
      cataracts among commercial airline pilots.

PMID- 16087846
TI  - Body mass index and age-related cataract: the Shihpai Eye Study.
AB  - OBJECTIVE: To investigate the association between body mass index (BMI)
      (calculated as weight in kilograms divided by the square of height in meters) and
      cataract in a metropolitan Asian elderly population. DESIGN: Population-based
      cross-sectional study. Age-related cataract was defined as any type of lens
      opacity (ie, nuclear, cortical, and posterior subcapsular opacity) with a Lens
      Opacities Classification System III grade of more than 2 in one or both eyes.
      Weight and height were measured by intensively trained interviewers. RESULTS: A
      total of 2045 subjects 65 years and older in Shihpai, Taipei, were invited to
      participate, and 1361 (66.6%) completed the survey. Of the subjects, 806 were
      diagnosed as having age-related cataracts. With a BMI of less than 21.3 as a
      reference point (odds ratio [OR], 1.00), a U-shaped relationship between BMI and
      nuclear opacity was demonstrated. A reverse U-shaped relationship was shown for
      cortical opacity. In the final multiple logistic regression models, BMI and
      BMI(2) were significantly related to nuclear opacity (BMI data: OR, 0.73 [95%
      confidence interval {CI}, 0.54-0.98]; and BMI(2) data: OR, 1.01 [95% CI, 1.00
      1.01]) and cortical opacity (BMI data: OR, 1.52 [95% CI, 1.04-2.34]; and BMI(2)
      data: OR, 0.99 [95% CI, 0.98-0.99]). Neither BMI nor BMI(2) was related to
      posterior subcapsular opacity. CONCLUSION: Body mass index is an independent risk
      factor for nuclear and cortical opacities, but in reverse direction to each
      other.

PMID- 16087847
TI  - Prevalence and burden of self-reported blindness, low vision, and visual
      impairment in the French community: a nationwide survey.
AB  - OBJECTIVE: To estimate the prevalence of self-reported visual impairment and its
      association with disabilities, handicaps, and socioeconomic consequences.
      METHODS: A national survey was conducted on a random stratified sample of 359 010
      French citizens living in the community; 21 760 subjects were selected at random
      and 16 945 persons (78%) agreed to further questioning. Four thousand ninety-one
      randomly selected caregivers were interviewed. Four subgroups of subjects were
      defined (blind or light perception only, low vision or still have form
      perception, other visual problems, and no visual problems). These were compared
      after adjustment for age, comorbidity, and household size differences. RESULTS:
      The prevalence of blindness was 0.10% and of low vision, 1.94%. Subjects with
      blindness needed assistance with daily activities more often than subjects with
      no visual problems; they also needed more house modifications. Many subjects with
      blindness (46.8%) and subjects with low vision (29.0%) were registered for social
      allowances. Subjects with blindness had fewer paid activities (4.5%) than
      subjects with no visual problems (20.7%). Social allowances increased
      considerably (by 277) between those with low vision and those with blindness.
      Monthly household incomes were lower (P<.001) for subjects with low vision (1255)
      and blindness (1587) than for subjects with no visual problems (1851). MAIN
      OUTCOME MEASURES: Collected data included social demography, home description,
      household income, handicaps, disabilities, social allowances, and daily
      activities. CONCLUSION: The results demonstrate associations between self
      reported visual impairment and daily living.

PMID- 16087848
TI  - Staining of the tenon capsule with trypan blue during enucleation surgery.

PMID- 16087849
TI  - Genotype-phenotype correlation in 2 Indian families with severe granular corneal
      dystrophy.
AB  - OBJECTIVES: To determine genotypes in 2 Indian families with severe granular
      corneal dystrophy, to document clinical and histopathologic features, and to
      attempt a genotype-phenotype correlation. METHODS: Mutation analysis of exon 12
      of the TGFBI gene was carried out in 9 individuals from 2 families. RESULTS: A C-
      >T mutation at residue 1710 of TGFBI complementary DNA, corresponding to an
      Arg555Trp mutation in keratoepithelin, was found in affected members of both
      families. In 5 patients, this mutation was homozygous, and it was heterozygous in
      the other 4. Clinical examination revealed a severe form of granular corneal
      dystrophy with early onset and superficial lesions in the homozygous individuals
      and a milder phenotype in the heterozygous individuals. Histopathologic
      evaluation of corneal specimens from 2 homozygous patients confirmed the presence
      of superficial granular deposits. CONCLUSIONS: To our knowledge, this is the
      first molecular and clinical characterization of severe granular corneal
      dystrophy in India. Genotype-phenotype correlation and comparison with earlier
      reports on this entity highlight the uniform expressivity of the Arg555Trp allele
      in homozygous individuals. CLINICAL RELEVANCE: Homozygous granular corneal
      dystrophy has a severe phenotype and can be recognized based on clinical and
      histopathologic features, especially in association with consanguinity or
      inbreeding.

PMID- 16087850
TI  - A more proactive approach is needed in glaucoma care.

PMID- 16087851
TI  - Diffuse retinal involvement in malignant nonteratoid medulloepithelioma of
      ciliary body in an adult.

PMID- 16087852
TI  - Bilateral choroiditis from Prototheca wickerhamii algaemia.

PMID- 16087853
TI  - Retinal ischemic syndrome, digestive tract small-vessel hyalinosis, and diffuse
      cerebral calcifications: a pediatric observation of a rare syndrome.

PMID- 16087854
TI  - Maculopathy and retinal degeneration in cobalamin C methylmalonic aciduria and
      homocystinuria.

PMID- 16087855
TI  - Stop mutations in exon 6 of the choroideremia gene, CHM, associated with
      preservation of the electroretinogram.

PMID- 16087856
TI  - Choroidal infarction following photodynamic therapy with verteporfin.

PMID- 16087857
TI  - Tamoxifen-induced regression of a choroidal metastasis in a man.

PMID- 16087858
TI  - Monocular temporal hemianopia associated with optic nerve hypoplasia.

PMID- 16087860
TI  - Effect of sham surgery on retinal function after subretinal transplantation of
      the artificial silicone retina.

PMID- 16087862
TI  - Detecting age-related macular degeneration: technologies are best compared when
      standardized.

PMID- 16087863
TI  - From the Cover: Location analysis of estrogen receptor alpha target promoters
      reveals that FOXA1 defines a domain of the estrogen response.
AB  - Nuclear receptors can activate diverse biological pathways within a target cell
      in response to their cognate ligands, but how this compartmentalization is
      achieved at the level of gene regulation is poorly understood. We used a genome
      wide analysis of promoter occupancy by the estrogen receptor alpha (ERalpha) in
      MCF-7 cells to investigate the molecular mechanisms underlying the action of
      17beta-estradiol (E2) in controlling the growth of breast cancer cells. We
      identified 153 promoters bound by ERalpha in the presence of E2. Motif-finding
      algorithms demonstrated that the estrogen response element (ERE) is the most
      common motif present in these promoters whereas conventional chromatin
      immunoprecipitation assays showed E2-modulated recruitment of coactivator AIB1
      and RNA polymerase II at these loci. The promoters were linked to known ERalpha
      targets but also to many genes not directly associated with the estrogenic
      response, including the transcriptional factor FOXA1, whose expression correlates
      with the presence of ERalpha in breast tumors. We found that ablation of FOXA1
      expression in MCF-7 cells suppressed ERalpha binding to the prototypic TFF1
      promoter (which contains a FOXA1 binding site), hindered the induction of TFF1
      expression by E2, and prevented hormone-induced reentry into the cell cycle.
      Taken together, these results define a paradigm for estrogen action in breast
      cancer cells and suggest that regulation of gene expression by nuclear receptors
      can be compartmentalized into unique transcriptional domains by means of
      licensing of their activity to cofactors such as FOXA1.

PMID- 16087864
TI  - Profile of Diane E. Griffin.

PMID- 16087865
TI  - Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I
      diabetes.
AB  - Mice deficient in programmed cell death 1 (PD-1, Pdcd1), an immunoinhibitory
      receptor belonging to the CD28/cytotoxic T lymphocyte-associated antigen-4
      family, spontaneously develop lupus-like autoimmune disease and autoimmune
      dilated cardiomyopathy on C57BL/6 and BALB/c backgrounds, respectively. However,
      how PD-1 deficiency induces different forms of autoimmune diseases on these two
      strains was unknown. Here, we report that PD-1 deficiency specifically
      accelerates the onset and frequency of type I diabetes in NOD (nonobese diabetic)
      mice, with strong T helper 1 polarization of T cells infiltrating into islets.
      These results suggest that PD-1 deficiency accelerates autoimmune predisposition
      of the background strain, leading to the induction of different forms of
      autoimmune diseases depending on the genetic background of the strain. Using NOD
      Pdcd1-/- mice as an efficient animal model of type I diabetes, we screened
      diabetes-susceptible loci by genetic linkage analysis. The diabetic incidence of
      NOD-Pdcd1-/- mice was controlled by five genetic loci, including three known
      recessive loci [Idd (insulin-dependent diabetes) 1, Idd17, and Idd20] and two
      previously unidentified dominant loci [Iddp (Idd under PD-1 deficiency) 1 and
      Iddp2].

PMID- 16087866
TI  - Complex regulation of somatic hypermutation by cis-acting sequences in the
      endogenous IgH gene in hybridoma cells.
AB  - To create high-affinity antibodies, B cells target a high rate of somatic
      hypermutation (SHM) to the Ig variable-region genes that encode the antigen
      binding site. This mutational process requires transcription and is triggered by
      activation-induced cytidine deaminase (AID), which converts deoxycytidine to
      deoxyuridine. Mistargeting of AID to non-Ig genes is thought to result in the
      malignant transformation of B cells, but the mechanism responsible for targeting
      SHM to certain DNA regions and not to others is largely unknown. Cis-acting
      elements have been proposed to play a role in directing the hypermutation
      machinery, but the motifs required for targeting SHM have been difficult to
      identify because many of the candidate elements, such as promoters or enhancers,
      are also required for transcription of Ig genes. Here we describe a system in
      cultured hybridoma cells in which transcription of the endogenous heavy-chain Ig
      gene continues in the absence of the core intronic enhancer (Emu) and its
      flanking matrix attachment regions (MARs). When AID is expressed in these cells,
      SHM occurred at the WT frequency even when Emu and the MARs were absent together.
      Interestingly, SHM occurred at less than the WT frequency when Emu or the MARs
      were individually absent. Our results suggest that these intronic regulatory
      elements can exert a complex influence on SHM that is separable from their role
      in regulating transcription.

PMID- 16087867
TI  - IL-10-dependent infectious tolerance after the treatment of experimental allergic
      encephalomyelitis with redirected CD4+CD25+ T lymphocytes.
AB  - How small numbers of CD4+CD25+ regulatory T cells suppress autoimmune responses
      in vivo is unclear. In this report we analyze the immunomodulatory activity of
      CD4+CD25+ T cells that are antigen-specifically redirected against myelin basic
      protein (MBP)89-101-specific autoreactive T cells by a MBP89-101-IA(s)-zeta
      chimeric receptor. We have previously shown that these redirected regulatory T
      cells are highly potent in treating a model autoimmune disease, experimental
      allergic encephalomyelitis. We show here that they have only limited effect in
      vivo on autoreactive T cell proliferation and therefore do not act by deleting or
      suppressing the expansion of pathologic effector cells. Rather, the redirected
      CD4+CD25+ T cells divert the pathologic T helper 1 self-specific T cell response
      to one characterized by high IL-10 and lower IL-4 production. Significantly, when
      isolated from the inducing CD4+CD25+ regulatory T cells, these self-specific T
      cells can independently suppress the autoreactive T cell response and
      experimental allergic encephalomyelitis development in an IL-10-dependent manner.
      These results provide evidence that CD4+CD25+ regulatory T cells can manipulate
      the adaptive immune response in vivo through the infectious induction of
      tolerance, specifically by promoting the formation of antigen-specific, IL-10
      secreting regulatory T cells.

PMID- 16087868
TI  - Nearsightedness of electronic matter.
AB  - In an earlier paper, W. Kohn had qualitatively introduced the concept of
      "nearsightedness" of electrons in many-atom systems. It can be viewed as
      underlying such important ideas as Pauling's "chemical bond," "transferability,"
      and Yang's computational principle of "divide and conquer." It describes the fact
      that, for fixed chemical potential, local electronic properties, such as the
      density n(r), depend significantly on the effective external potential only at
      nearby points. Changes of that potential, no matter how large, beyond a distance
      R have limited effects on local electronic properties, which rapidly tend to zero
      as a function of R. In the present paper, the concept is first sharpened for
      representative models of uncharged fermions moving in external potentials, and
      then the effects of electron-electron interactions and of perturbing external
      charges are discussed.

PMID- 16087869
TI  - Tissue morphogenesis and vascular stability require the Frem2 protein, product of
      the mouse myelencephalic blebs gene.
AB  - Adhesive properties of cells undergoing morphogenetic rearrangements can be
      regulated either at the cellular level or by altering the environment in which
      rearrangements occur. Here, we describe the identification of a mutation
      (my(F11)) in the mouse extracellular matrix component Frem2, and provide evidence
      that suggests Frem2 expression creates an environment conducive to morphogenetic
      events. Loss of Frem2 function results in defects in developmental events
      associated with morphogenetic rearrangements of the vasculature and of tissues
      arising from all germ layers. The Frem2 transcript is restricted both spatially
      and temporally and appears in advance of cell rearrangement events. Thus,
      expression of Frem2 may dynamically alter the extracellular matrix to provide a
      substrate for cell migration and rearrangements during embryogenesis.

PMID- 16087870
TI  - An evolutionary constraint: strongly disfavored class of change in DNA sequence
      during divergence of cis-regulatory modules.
AB  - The DNA of functional cis-regulatory modules displays extensive sequence
      conservation in comparisons of genomes from modestly distant species. Patches of
      sequence that are several hundred base pairs in length within these modules are
      often seen to be 80-95% identical, although the flanking sequence cannot even be
      aligned. However, it is unlikely that base pairs located between the
      transcription factor target sites of cis-regulatory modules have sequence
      dependent function, and the mechanism that constrains evolutionary change within
      cis-regulatory modules is incompletely understood. We chose five functionally
      characterized cis-regulatory modules from the Strongylocentrotus purpuratus (sea
      urchin) genome and obtained orthologous regulatory and flanking sequences from a
      bacterial artificial chromosome genome library of a congener, Strongylocentrotus
      franciscanus. As expected, single-nucleotide substitutions and small indels occur
      freely at many positions within the regulatory modules of these two species, as
      they do outside the regulatory modules. However, large indels (>20 bp) are
      statistically almost absent within the regulatory modules, although they are
      common in flanking intergenic or intronic sequence. The result helps to explain
      the patterns of evolutionary sequence divergence characteristic of cis-regulatory
      DNA.

PMID- 16087871
TI  - Direct measurement of electrical transport through single DNA molecules of
      complex sequence.
AB  - Seemingly contradicting results raised a debate over the ability of DNA to
      transport charge and the nature of the conduction mechanisms through it. We
      developed an experimental approach for measuring current through DNA molecules,
      chemically connected on both ends to a metal substrate and to a gold
      nanoparticle, by using a conductive atomic force microscope. Many samples could
      be made because of the experimental approach adopted here, which enabled us to
      obtain reproducible results with various samples, conditions, and measurement
      methods. We present multi-leveled evidence for charge transport through 26-bp
      long dsDNA of a complex sequence, characterized by S-shaped current-voltage
      curves that show currents >220 nA at 2 V. This significant observation implies
      that a coherent or band transport mechanism takes over for bias potentials
      leading to high currents (>1 nA).

PMID- 16087872
TI  - In situ measurement of solute transport in the bone lacunar-canalicular system.
AB  - Solute transport through the bone lacunar-canalicular system is believed to be
      essential for osteocyte survival and function but has proved difficult to
      measure. We report an approach that permits direct measurement of real-time
      solute movement in intact bones. By using fluorescence recovery after
      photobleaching, the movement of a vitally injected fluorescent dye (sodium
      fluorescein) among individual osteocytic lacunae was visualized in situ beneath
      the periosteal surface of mouse cortical bone at depths up to 50 microm with
      laser scanning confocal microscopy. Transport was analyzed by using a two
      compartment mathematical model of solute diffusion that accounted for the
      characteristic anatomical features of the lacunar-canalicular system. The
      diffusion coefficient of fluorescein (376 Da) was determined to be 3.3 +/- 0.6 x
      10(-6) cm2/sec, which is 62% of its diffusion coefficient in water and is similar
      to diffusion coefficients measured for comparably sized molecules in cartilage.
      The diffusion of fluorescein in bone is also consistent with the presence of an
      osteocyte pericellular matrix whose structure resembles that proposed for the
      endothelial glycocalyx [Squire, J. M., Chew, M., Nneji, G., Neal, C., Barry, J. &
      Michel, C. (2001) J. Struct. Biol. 136, 239-255]. To our knowledge, this is the
      first instance where the dynamics of molecular movement has been measured
      directly in the bone lacunar-canalicular system. This in situ imaging approach
      should also facilitate the analysis of convection-based transport mechanisms in
      bones of living animals.

PMID- 16087873
TI  - Targeted disruption of Mig-6 in the mouse genome leads to early onset
      degenerative joint disease.
AB  - Degenerative joint disease, also known as osteoarthritis, is the most common
      joint disorder in human beings. The molecular mechanism underlying this disease
      is not fully understood. Here, we report that disruption of mitogen-inducible
      gene 6 (Mig-6) in mice by homologous recombination leads to early onset
      degenerative joint disease, which is revealed by simultaneous enlargement and
      deformity of multiple joints, degradation of articular cartilage, and the
      development of bony outgrowths or osteophyte formation within joint space. The
      osteophyte formation appears to be derived from proliferation of mesenchymal
      progenitor cells followed by differentiation into chondrocytes. Absence of the
      Rag2 gene does not rescue the joint phenotype, excluding a role for the acquired
      immune system in the development of this disease. Our results provide insight
      into the mechanism of osteoarthritis by showing that loss of Mig-6 leads to early
      onset of this disease, implying that this gene or its pathway is important in
      normal joint maintenance. Because of the striking similarity of osteoarthritis in
      humans and mice, the Mig-6 mutant mouse should provide a useful animal model for
      studying the mechanism of this disease and for testing drugs or therapies for
      treating osteoarthritis.

PMID- 16087874
TI  - Structure and fluctuations of a single floating lipid bilayer.
AB  - A single lipid molecular bilayer of 17 or 18 carbon chain phosphocholines,
      floating in water near a flat wall, is prepared in the bilayer gel phase and then
      heated to the fluid phase. Its structure (electron density profile) and height
      fluctuations are determined by using x-ray reflectivity and non-specular
      scattering. By fitting the off-specular signal to that calculated for a two
      dimensional membrane using a Helfrich Hamiltonian, we determine the three main
      physical quantities that govern the bilayer height fluctuations: The wall
      attraction potential is unexpectedly low; the surface tension, roughly
      independent on chain length and temperature, is moderate (approximately 5 x 10(
      4) J.m(-2)) but large enough to dominate the intermediate range of the
      fluctuation spectrum; and the bending modulus abruptly decreases by an order-of
      magnitude from 10(-18) J to 10(-19) J at the bilayer gel-to-fluid transition.

PMID- 16087875
TI  - Vitamin C biosynthesis in trypanosomes: a role for the glycosome.
AB  - The capacity to synthesize vitamin C (ascorbate) is widespread in eukaryotes but
      is absent from humans. The last step in the biosynthetic pathway involves the
      conversion of an aldonolactone substrate to ascorbate, a reaction catalyzed by
      members of an FAD-dependent family of oxidoreductases. Here we demonstrate that
      both the African trypanosome, Trypanosoma brucei, and the American trypanosome,
      Trypanosoma cruzi, have the capacity to synthesize vitamin C and show that this
      reaction occurs in a unique single-membrane organelle, the glycosome. The
      corresponding T. brucei flavoprotein (TbALO) obeys Michaelis-Menten kinetics and
      can utilize both L-galactono-gamma-lactone and D-arabinono-gamma-lactone as
      substrate, properties characteristic of plant and fungal enzymes. We could detect
      no activity toward the mammalian enzyme substrate L-gulono-gamma-lactone. TbALO
      null mutants (bloodstream form) were found to display a transient growth defect,
      a trait that was enhanced when they were cultured in medium in which the
      essential serum component had been pretreated with ascorbate oxidase to deplete
      vitamin C. It is implicit, therefore, that bloodstream-form trypanosomes also
      possess a capacity for ascorbate transport.

PMID- 16087876
TI  - Crystallization of a mammalian membrane protein overexpressed in Saccharomyces
      cerevisiae.
AB  - The Ca2+-ATPase SERCA1a (sarcoplasmic-endoplasmic reticulum Ca2+-ATPase isoform
      1a) from rabbit has been overexpressed in Saccharomyces cerevisiae. This membrane
      protein was purified by avidin agarose affinity chromatography based on natural
      biotinylation in the expression host, followed by HPLC gel filtration. Both the
      functional and structural properties of the overexpressed protein validate the
      method. Thus, calcium-dependent ATPase activity and calcium transport are
      essentially intact after reconstitution in proteoliposomes. Moreover, the
      recombinant protein crystallizes in a form that is isomorphous to the native
      SERCA1a protein from rabbit, and the diffraction properties are similar. This
      represents a successful crystallization of a mammalian membrane protein derived
      from a heterologous expression system, and it opens the way for the study of
      mutant forms of SERCA1a.

PMID- 16087877
TI  - The striatofugal fiber system in primates: a reevaluation of its organization
      based on single-axon tracing studies.
AB  - The current model of basal ganglia rests on the idea that the striatofugal system
      is composed of two separate (direct and indirect) pathways originating from
      distinct cell populations in the striatum. The striatum itself is divided into
      two major compartments, the striosomes and the matrix, which differ by their
      neurochemical makeup and input/output connections. Here, neurons located in
      either striosomes or the extrastriosomal matrix in squirrel monkeys were injected
      with biotin dextran amine, and their labeled axons were entirely reconstructed
      with a camera lucida. Twenty-four of 27 reconstructed axons arborized into the
      three main striatal targets (external pallidum, globus pallidus, and substantia
      nigra pars reticulata), a finding that is at odds with the concept of a dual
      striatofugal system. Axons of striosomal neurons formed several columnar terminal
      fields in the substantia nigra pars reticulata. These data indicate that the
      substantia nigra pars compacta is neither the only nor the main target of
      striosomal neurons, a finding that calls for a reevaluation of the organization
      of the striatonigral projection system.

PMID- 16087878
TI  - Carbon nanotubes as multifunctional biological transporters and near-infrared
      agents for selective cancer cell destruction.
AB  - Biological systems are known to be highly transparent to 700- to 1,100-nm near
      infrared (NIR) light. It is shown here that the strong optical absorbance of
      single-walled carbon nanotubes (SWNTs) in this special spectral window, an
      intrinsic property of SWNTs, can be used for optical stimulation of nanotubes
      inside living cells to afford multifunctional nanotube biological transporters.
      For oligonucleotides transported inside living cells by nanotubes, the oligos can
      translocate into cell nucleus upon endosomal rupture triggered by NIR laser
      pulses. Continuous NIR radiation can cause cell death because of excessive local
      heating of SWNT in vitro. Selective cancer cell destruction can be achieved by
      functionalization of SWNT with a folate moiety, selective internalization of
      SWNTs inside cells labeled with folate receptor tumor markers, and NIR-triggered
      cell death, without harming receptor-free normal cells. Thus, the transporting
      capabilities of carbon nanotubes combined with suitable functionalization
      chemistry and their intrinsic optical properties can lead to new classes of novel
      nanomaterials for drug delivery and cancer therapy.

PMID- 16087879
TI  - Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates
      pathology in a Huntington's disease mouse model.
AB  - In investigating the role of metal ions in the pathogenesis of Huntington's
      disease, we examined the effects of clioquinol, a metal-binding compound
      currently in clinical trials for Alzheimer's disease treatment, on mutant
      huntingtin-expressing cells. We found that PC12 cells expressing polyglutamine
      expanded huntingtin exon 1 accumulated less mutant protein and showed decreased
      cell death when treated with clioquinol. This effect was polyglutamine-length
      specific and did not alter mRNA levels or protein degradation rates. Clioquinol
      treatment of transgenic Huntington's mice (R6/2) improved behavioral and
      pathologic phenotypes, including decreased huntingtin aggregate accumulation,
      decreased striatal atrophy, improved rotarod performance, reduction of weight
      loss, normalization of blood glucose and insulin levels, and extension of
      lifespan. Our results suggest that clioquinol is a candidate therapy for
      Huntington's disease and other polyglutamine-expansion diseases.

PMID- 16087880
TI  - Epithelial membrane protein-1 is a biomarker of gefitinib resistance.
AB  - We describe a molecular resistance biomarker to gefitinib, epithelial membrane
      protein-1 (EMP-1). Gefitinib is a small-molecule inhibitor that competes for the
      ATP-binding site on EGF receptor (EGFR) and has been approved for patients with
      advanced lung cancers. Treatment with gefitinib has resulted in clinical benefit
      in patients, and, recently, heterozygous somatic mutations within the EGFR
      catalytic domain have been identified as a clinical correlate to objective
      response to gefitinib. However, clinical resistance to gefitinib limits the
      utility of this therapeutic to a fraction of patients, and objective clinical
      responses are rare. We aimed to assess the molecular phenotype and mechanism of
      in vivo gefitinib resistance in xenograft models and in patient samples. We
      generated in vivo gefitinib-resistance models in an adenocarcinoma xenograft
      model by serially passaging tumors in nude mice in presence of gefitinib until
      resistance was acquired. EMP-1 was identified as a surface biomarker whose
      expression correlated with acquisition of gefitinib resistance. EMP-1 expression
      was further correlated with lack of complete or partial response to gefitinib in
      lung cancer patient samples as well as clinical progression to secondary
      gefitinib resistance. EMP-1 expression and acquisition of gefitinib clinical
      resistance was independent of gefitinib-sensitizing EGFR somatic mutations. This
      report suggests the role of the adhesion molecule, EMP-1, as a biomarker of
      gefitinib clinical resistance, and further suggests a probable cross-talk between
      this molecule and the EGFR signaling pathway.

PMID- 16087881
TI  - Single-nucleotide polymorphism detection with "wire-like" DNA probes that display
      quasi "on-off" digital action.
AB  - Establishing a reliable genotyping protocol is a critical matter in post-sequence
      genetics. In this article, we describe a highly sensitive electrochemical
      detection of complementary DNAs (up to 43-mer) based on hole transport with
      molecular-scale, "wire-like" DNA probes. The presence of a single-base mismatch
      in the DNA duplexes caused a dramatic decrease in the electrochemical response.
      We applied this method to detect all of the possible transition and transversion
      SNPs and achieved "on-off"-type discrimination of fully complementary DNAs from
      their SNPs. Furthermore, naturally occurring polymorphisms, "hot spots" from the
      p53 gene, could clearly be distinguished from wild type by using our methodology.

PMID- 16087883
TI  - Precocious metamorphosis in transgenic silkworms overexpressing juvenile hormone
      esterase.
AB  - Insect growth and development are intricately regulated by the titers of juvenile
      hormones (JHs) and ecdysteroids (and/or their metabolites) in the insect
      hemolymph. Hydrolysis of the methyl ester of JH by a JH-specific esterase (JHE)
      is a key pathway for the degradation of JH. Here, we generate transgenic silkworm
      strains that overexpress JHE by using the binary GAL4/UAS system. Overexpression
      of JHE from the embryonic stage resulted in larval-pupal metamorphosis after the
      third stadium, two stadia earlier than that observed in wild-type insects. This
      precocious metamorphosis suggests that JHs are not critical for normal
      development of embryo or larva before the second molt in Lepidoptera (moths and
      butterflies). Our transgenic approach allowed us to dissect the function of key
      physiological events that occur from embryogenesis. Until now, these types of
      studies were possible only in later larval stadia by using physical techniques
      such as allatectomy or the application of JH analogues. We believe that our
      system will allow further pioneering studies in insect physiology.

PMID- 16087882
TI  - Circuit topology and the evolution of robustness in two-gene circadian
      oscillators.
AB  - Many parameters driving the behavior of biochemical circuits vary extensively and
      are thus not fine-tuned. Therefore, the topology of such circuits (the who
      interacts-with-whom) is key to understanding their central properties. I here
      explore several hundred different topologies of a simple biochemical model of
      circadian oscillations to ask two questions: Do different circuits differ
      dramatically in their robustness to parameter change? If so, can a process of
      gradual molecular evolution find highly robust topologies when starting from less
      robust topologies? I find that the distribution of robustness among different
      circuit topologies is highly skewed: Most show low robustness, whereas very few
      topologies are highly robust. To address the second evolutionary question, I
      define a topology graph, each of whose nodes corresponds to one circuit topology
      that shows circadian oscillations. Two nodes in this graph are connected if they
      differ by only one regulatory interaction within the circuit. For the circadian
      oscillator I study, most topologies are connected in this graph, making
      evolutionary transitions from low to high robustness easy. A similar approach has
      been used to study the evolution of robustness in biological macromolecules, with
      similar results. This suggests that the same principles govern the evolution of
      robustness on different levels of biological organization. The regulatory
      interlocking of several oscillating gene products in biological circadian
      oscillators may exist because it provides robustness.

PMID- 16087884
TI  - Molecular evidence for an activator-inhibitor mechanism in development of
      embryonic feather branching.
AB  - The developmental basis of morphological complexity remains a central question in
      developmental and evolutionary biology. Feathers provide a unique system to
      analyze the development of complex morphological novelties. Here, we describe the
      interactions between Sonic hedgehog (Shh) and bone morphogenetic protein 2 (Bmp2)
      signaling during feather barb ridge morphogenesis. We demonstrate that activator
      inhibitor models of Shh and Bmp2 signaling in the tubular feather epithelium are
      sufficient to explain the initial formation of a meristic pattern of barb ridges
      and the observed variation in barb morphogenesis in chick natal down feathers.
      Empirical tests support the assumptions of the model that, within the feather
      ectoderm, Shh (activator) up-regulates its own transcription and that of Bmp2
      (inhibitor), whereas Bmp2 signaling down-regulates Shh expression. More complex
      models incorporating a second activator and dorsal/ventral polarized modification
      of activator signaling can produce all of the barb morphogenesis patterns
      observed during the growth of more complex branched pennaceous feathers: new barb
      ridge formation, helical growth, and barb ridge fusion. An integrated model of
      feather morphogenesis and evolution suggests that plumulaceous feather structure
      evolved by the establishment of activator-inhibitor interactions between Shh and
      Bmp2 signaling in the basal epithelium of the feather germ. Subsequently,
      pennaceous feather structure evolved through the integration of barb ridge
      morphogenesis with a second, local inhibitor and a dorsal/ventral signal gradient
      within the feather. The model is congruent with paleontological evidence that
      plumulaceous feathers are primitive to pennaceous feathers.

PMID- 16087885
TI  - Unsupervised learning of natural languages.
AB  - We address the problem, fundamental to linguistics, bioinformatics, and certain
      other disciplines, of using corpora of raw symbolic sequential data to infer
      underlying rules that govern their production. Given a corpus of strings (such as
      text, transcribed speech, chromosome or protein sequence data, sheet music,
      etc.), our unsupervised algorithm recursively distills from it hierarchically
      structured patterns. The adios (automatic distillation of structure) algorithm
      relies on a statistical method for pattern extraction and on structured
      generalization, two processes that have been implicated in language acquisition.
      It has been evaluated on artificial context-free grammars with thousands of
      rules, on natural languages as diverse as English and Chinese, and on protein
      data correlating sequence with function. This unsupervised algorithm is capable
      of learning complex syntax, generating grammatical novel sentences, and proving
      useful in other fields that call for structure discovery from raw data, such as
      bioinformatics.

PMID- 16087886
TI  - Myc interacts genetically with Tip48/Reptin and Tip49/Pontin to control growth
      and proliferation during Drosophila development.
AB  - The transcription factor dMyc is the sole Drosophila ortholog of the vertebrate c
      myc protooncogenes and a central regulator of growth and cell-cycle progression
      during normal development. We have investigated the molecular basis of dMyc
      function by analyzing its interaction with the putative transcriptional cofactors
      Tip48/Reptin (Rept) and Tip49/Pontin (Pont). We demonstrate that Rept and Pont
      have conserved their ability to bind to Myc during evolution. All three proteins
      are required for tissue growth in vivo, because mitotic clones mutant for either
      dmyc, pont,or rept suffer from cell competition. Most importantly, pont shows a
      strong dominant genetic interaction with dmyc that is manifested in the duration
      of development, rates of survival and size of the adult animal and, in
      particular, of the eye. The molecular basis for these effects may be found in the
      repression of certain target genes, such as mfas, by dMyc:Pont complexes. These
      findings indicate that dMyc:Pont complexes play an essential role in the control
      of cellular growth and proliferation during normal development.

PMID- 16087887
TI  - Subdomains for transport via plasmodesmata corresponding to the apical-basal axis
      are established during Arabidopsis embryogenesis.
AB  - The axial body pattern of Arabidopsis is determined during embryogenesis by auxin
      signaling and differential gene expression. Here we demonstrate that another
      pathway, cell-to-cell communication through plasmodesmata (PD), is regulated
      during apical-basal pattern formation. The SHOOT MERISTEMLESS (STM) promoter was
      used to drive expression in the shoot apical meristem (SAM) and a subset of cells
      at the base of the hypocotyl of 1x,2x, and 3x soluble green fluorescent proteins
      (sGFPs), and the P30 movement protein of Tobacco mosaic virus (TMV)
      translationally fused to 1x and 2x sGFP. In the early heart stage, 2x sGFP (54
      kDa) moves throughout the whole embryo, whereas 3x sGFP (81 kDa) shows more
      restricted movement. As the embryo develops, PD apertures are down regulated to
      form local subdomains allowing transport of different sized tracers. For example,
      movement of 2x sGFP to the cotyledon, and 3x sGFP to root tips, becomes
      restricted. Subdomains of cell-to-cell transport align with the apical-basal
      embryo body axis and correspond to the shoot apex, cotyledons, hypocotyl, and
      root. Studies with P30-GFP fusions reinforce the distinction between embryonic
      symplastic subdomains. Although P30 targets embryo cell walls as puncta
      (diagnostic for functional localization of P30 to PD in adult plants), P30 cannot
      dilate embryonic PD to overcome the barriers for transport between symplastic
      subdomains, suggesting that specific boundaries separate symplastic subdomains of
      the embryo. Thus, cell-to-cell communication via plasmodesmata conveys positional
      information critical to establish the axial body pattern during embryogenesis in
      Arabidopsis.

PMID- 16087888
TI  - Convergent evolution of chemical defense in poison frogs and arthropod prey
      between Madagascar and the Neotropics.
AB  - With few exceptions, aposematically colored poison frogs sequester defensive
      alkaloids, unchanged, from dietary arthropods. In the Neotropics, myrmicine and
      formicine ants and the siphonotid millipede Rhinotus purpureus are dietary
      sources for alkaloids in dendrobatid poison frogs, yet the arthropod sources for
      Mantella poison frogs in Madagascar remained unknown. We report GC-MS analyses of
      extracts of arthropods and microsympatric Malagasy poison frogs (Mantella)
      collected from Ranomafana, Madagascar. Arthropod sources for 11 "poison frog"
      alkaloids were discovered, 7 of which were also detected in microsympatric
      Mantella. These arthropod sources include three endemic Malagasy ants,
      Tetramorium electrum, Anochetus grandidieri, and Paratrechina amblyops
      (subfamilies Myrmicinae, Ponerinae, and Formicinae, respectively), and the
      pantropical tramp millipede R. purpureus. Two of these ant species, A.
      grandidieri and T. electrum, were also found in Mantella stomachs, and ants
      represented the dominant prey type (67.3% of 609 identified stomach arthropods).
      To our knowledge, detection of 5,8-disubstituted (ds) indolizidine iso-217B in T.
      electrum represents the first izidine having a branch point in its carbon
      skeleton to be identified from ants, and detection of 3,5-ds pyrrolizidine 251O
      in A. grandidieri represents the first ponerine ant proposed as a dietary source
      of poison frog alkaloids. Endemic Malagasy ants with defensive alkaloids (with
      the exception of Paratrechina) are not closely related to any Neotropical species
      sharing similar chemical defenses. Our results suggest convergent evolution for
      the acquisition of defensive alkaloids in these dietary ants, which may have been
      the critical prerequisite for subsequent convergence in poison frogs between
      Madagascar and the Neotropics.

PMID- 16087889
TI  - Molecular basis of alanine discrimination in editing site.
AB  - AlaX is the homologue of the class II alanyl-tRNA synthetase editing domain and
      has been shown to exhibit autonomous editing activity against mischarged
      tRNA(Ala). Here, we present the structures of AlaX from the archaeon Pyrococcus
      horikoshii in apo form, complexed with zinc, and with noncognate amino acid l
      serine and zinc. Together with mutational analysis, we demonstrated that the
      conserved Thr-30 hydroxyl group located near the beta-methylene of the bound
      serine is responsible for the discrimination of noncognate serine from cognate
      alanine, based on their chemical natures. Furthermore, we confirmed that the
      conserved Gln-584 in alanyl-tRNA synthetase, which corresponds to Thr-30 of AlaX,
      is also critical for discrimination. These observations strongly suggested
      conservation of the chemical discrimination among trans- and cis-editing of
      tRNA(Ala).

PMID- 16087891
TI  - Additional remains of Wadilemur elegans, a primitive stem galagid from the late
      Eocene of Egypt.
AB  - The late Eocene prosimian Wadilemur elegans from the Jebel Qatrani Formation,
      northern Egypt, was originally interpreted as an anchomomyin adapiform primate
      based on limited information from the lower molars and distal premolars. Recently
      recovered fossils attributable to this species, including a proximal femur, the
      fourth upper premolar and first and second upper molars, and a mandible
      preserving the lower second premolar and lower canine and incisor alveoli, reveal
      a number of derived morphological similarities shared with crown strepsirrhines
      and, in particular, Miocene-to-Recent stem and crown galagids, to the exclusion
      of known adapiforms. Phylogenetic analysis of 359 morphological features scored
      across 95 living and extinct crown primate taxa supports a stem galagid placement
      for Wadilemur and older Saharagalago, and a close relationship between crown
      strepsirrhines and the Eocene African taxa "Anchomomys" milleri, Djebelemur, and
      Plesiopithecus (none of which appear to be closely related to European
      anchomomyins). This scheme of relationships supports the hypothesis that crown
      Strepsirrhini is of Afro-Arabian origin and that lemuriforms likely colonized
      Madagascar by crossing the Mozambique Channel. Wadilemur's known dental and
      postcranial morphology provides additional support for the hypothesis that
      galagids and lorisids had diverged by the close of the middle Eocene, and, by
      bolstering the approximately 37 million-year-old calibration point for crown
      lorisiform origins provided by Saharagalago, indirect support for the hypothesis
      of an ancient origin of crown Strepsirrhini and crown Primates.

PMID- 16087890
TI  - Three-dimensional structure of the quorum-quenching N-acyl homoserine lactone
      hydrolase from Bacillus thuringiensis.
AB  - The three-dimensional structure of the N-acyl-l-homoserine lactone hydrolase (AHL
      lactonase) from Bacillus thuringiensis has been determined, by using single
      wavelength anomalous dispersion (SAD) phasing, to 1.6-angstroms resolution. AHLs
      are produced by many Gram-negative bacteria as signaling molecules used in quorum
      sensing pathways that indirectly sense cell density and regulate communal
      behavior. Because of their importance in pathogenicity, quorum-sensing pathways
      have been suggested as potential targets for the development of novel
      therapeutics. Quorum-sensing can be disrupted by enzymes evolved to degrade these
      lactones, such as AHL lactonases. These enzymes are members of the metallo-beta
      lactamase superfamily and contain two zinc ions in their active sites. The zinc
      ions are coordinated to a number of ligands, including a single oxygen of a
      bridging carboxylate and a bridging water/hydroxide ion, thought to be the
      nucleophile that hydrolyzes the AHLs to ring-opened products, which can no longer
      act as quorum signals.

PMID- 16087892
TI  - Reversible cervical hydromyelia in subacute combined degeneration.

PMID- 16087893
TI  - Women in neurology.

PMID- 16087894
TI  - Herpes zoster and the prevention of postherpetic neuralgia: beyond antiviral
      therapy.

PMID- 16087895
TI  - Sublime diagnosis of Lyme neuroborreliosis.

PMID- 16087896
TI  - Facilitating acute stroke recovery with magnetic fields?

PMID- 16087897
TI  - Camptocormia: pathogenesis, classification, and response to therapy.
AB  - Originally considered a psychogenic disorder, camptocormia, an abnormal posture
      with marked flexion of thoracolumbar spine that abates in the recumbent position,
      is becoming an increasingly recognized feature of parkinsonian and dystonic
      disorders. Prior reports were limited by sample size, short follow-up, and
      paucity of data on response to therapy. The authors reviewed 16 patients
      evaluated in their PD Center and Movement Disorders Clinic diagnosed with
      camptocormia. In addition to detailed neurologic assessment all patients were
      videotaped. The mean age was 64.9 +/- 17.4 years, mean age at onset of neurologic
      symptoms was 51.5 +/- 19.9 years, duration from onset of neurologic symptoms to
      development of camptocormia was 6.7 +/- 7.6 years, and the mean duration of
      camptocormia was 4.5 +/- 3.9 years. Of the 16 patients, 11 (68.8%) had Parkinson
      disease (PD); others had dystonia (n = 4) and Tourette syndrome (n = 1). Twelve
      patients received levodopa, with minimal or no improvement in the camptocormia.
      Nine patients received botulinum toxin type A injections into the rectus
      abdominus, with notable improvement in their camptocormia in four. One patient
      underwent bilateral subthalamic nucleus deep brain stimulation for PD, but there
      was no improvement in camptocormia. Based on this series and a thorough review of
      the literature of camptocormia, head drop, and bent spine syndrome, the authors
      propose etiologic classification of camptocormia and conclude that this
      heterogeneous disorder has multiple etiologies and variable response to systemic
      and local therapies.

PMID- 16087898
TI  - The impact of standardized stroke orders on adherence to best practices.
AB  - BACKGROUND: Standardized order templates have been credited with improving care
      for several common medical conditions. The authors sought to determine whether
      use of standard orders would be associated with improvement in stroke care.
      METHODS: All patients with a discharge diagnosis of ischemic stroke were
      identified from seven hospitals in California participating in a CDC-sponsored
      Coverdell Acute Stroke Pilot Registry. The authors tracked six points of care:
      thrombolysis, receipt of antithrombotic medications within 48 hours, prophylaxis
      for deep venous thrombosis (DVT), smoking cessation counseling, and prescription
      of lipid-lowering and antithrombotic medications at discharge. Scoring was based
      on optimal treatment, defined as receiving or having a valid contraindication to
      a given intervention. Baseline scores in year 1 were compared to those in year 2,
      after implementation of an intervention based upon standardized stroke orders.
      RESULTS: Overall, rates of optimal treatment improved for patients treated in
      year 2 (n = 226) compared to year 1 (n = 187), with 63% of patients receiving a
      perfect score in year 2 compared to 44% in year 1 (p < 0.0001). Rates
      significantly improved in four of six hospitals, when the hospital was considered
      the unit of intervention, and for four of the six specific measures. A seventh
      hospital that participated in the registry but did not implement standardized
      orders showed no improvement in optimal treatment. CONCLUSIONS: Implementation of
      standardized stroke orders and registry monitoring was associated with
      improvements in utilization of a number of proven interventions. Although these
      data are observational, they demonstrate the potential impact of simple system
      wide interventions in improving care of stroke.

PMID- 16087899
TI  - Hemostatic markers of recanalization in patients with ischemic stroke treated
      with rt-PA.
AB  - OBJECTIVE: To determine whether pretreatment markers of coagulation and
      fibrinolysis are related to recanalization and functional outcome. METHODS: The
      authors included patients treated with IV rt-PA with occlusion on baseline
      transcranial Doppler (Thrombolysis in Brain Ischemia [TIBI] criteria) in whom
      recanalization within 6 hours was monitored. At baseline, the authors recorded
      data about demographics, vascular risk factors, the NIH Stroke Scale (NIHSS)
      score, early CT signs, etiology, blood glucose, and time to rt-PA. The authors
      also measured plasmatic markers of coagulation (fibrinogen, prothrombin fragments
      1 + 2, Factor XIII, Factor VII) and fibrinolysis (alpha2-antiplasmin, Plasminogen
      Activator Inhibitor, Functional Thrombin Activatable Fibrinolysis Inhibitor
      [fTAFI]). A favorable outcome was defined as a modified Rankin score < 2 at 3
      months. RESULTS: The authors studied 63 patients with a mean age of 67.3 +/- 12.5
      years. The median NIHSS score was 16. Patients who recanalized had lower
      concentrations of alpha2-antiplasmin (87.5 +/- 18% vs 96.5 +/- 12.5%, p = 0.023)
      and fTAFI (91.7 +/- 26.7% vs 104.4 +/- 21%, p = 0.039). A multivariant logistic
      regression analysis showed that the level of alpha2-antiplasmin was the only
      predictive variable of recanalization (OR 0.95, 95% CI 0.91, 0.99, p = 0.038),
      while the NIHSS score was the only predictive variable of functional outcome (OR
      0.81, 95% CI 0.72, 0.92, p = 0.001). CONCLUSION: Baseline levels of alpha2
      antiplasmin were predictive of recanalization but were not related to the long
      term outcome in patients treated with rt-PA within the first 3 hours.

PMID- 16087900
TI  - Population-based study of delays in carotid imaging and surgery and the risk of
      recurrent stroke.
AB  - BACKGROUND: Benefit from carotid endarterectomy is greatest when performed within
      2 weeks of a presenting TIA or stroke and decreases rapidly thereafter.
      OBJECTIVE: To determine the delays to carotid imaging and endarterectomy in
      Oxfordshire, UK, and the consequences for the effectiveness of stroke prevention.
      METHODS: All patients undergoing carotid imaging for ischemic retinal or cerebral
      TIA or stroke were identified in two populations: the population of Oxfordshire,
      UK (n = 680,772), from April 1, 2002, to March 31, 2003, and the Oxford Vascular
      Study (OXVASC) subpopulation (n = 92,000) from April 1, 2002, to March 31, 2004.
      The times from presenting event to referral, scanning, and endarterectomy
      (Oxfordshire population) and the risk of stroke prior to endarterectomy in
      patients with > or = 50% symptomatic carotid stenosis (OXVASC population) were
      determined. RESULTS: Among 853 patients who had carotid imaging in the
      Oxfordshire population, median (interquartile range) times from presenting event
      to referral, scanning, and endarterectomy were 9 (3 to 30), 33 (12 to 62), and
      100 (59 to 137) days. Eighty-five patients were found to have 50 to 99%
      symptomatic stenosis, of whom 49 had endarterectomy. Only 3 (6%) had surgery
      within 2 weeks of their presenting event and only 21 (43%) within 12 weeks. The
      risk of stroke prior to endarterectomy in the OXVASC subpopulation with > or =
      50% stenosis was 21% (8 to 34%) at 2 weeks and 32% (17 to 47%) at 12 weeks, in
      half of which strokes were disabling or fatal. CONCLUSION: Delays to carotid
      imaging and endarterectomy after TIA or stroke in the United Kingdom are similar
      to those reported in several other countries and are associated with very high
      risks of otherwise preventable early recurrent stroke.

PMID- 16087901
TI  - Subcortical vascular dementia: integrating neuropsychological and neuroradiologic
      data.
AB  - BACKGROUND: Research criteria for subcortical vascular dementia are based on
      radiologic evidence of vascular pathology and greater impairment on tests of
      executive control than memory. The relationship(s) between neuroradiological
      evidence of subcortical vascular disease and neuropsychological impairments has
      not been specified. OBJECTIVE: To define these research criteria, the authors
      rated the severity of MRI white matter abnormalities (WMAs) and
      neuropsychological data from patients with dementia. METHODS: Sixty-nine
      outpatients who met the criteria for dementia were studied with
      neuropsychological tests that assessed executive (mental) control, declarative
      memory, visuoconstruction (clock drawing), and language (semantic category
      fluency). MRI-WMAs were rated using a leukoaraiosis (LA) scale (range 0 to 40).
      RESULTS: First, regression analyses demonstrated that neuropsychological measures
      accounted for 60.7% of the variance in WMA severity (47.3% of this variance
      attributable to executive/visuoconstructive test performance, 13.4% attributable
      to memory/language test performance). Second, patients were grouped according to
      the severity of WMAs (i.e., low, moderate, and severe white matter groups). Only
      patients with mild WMA (mean LA = 3.61 +/- 2.63, approximately 2.4 to 15.6% of
      the subcortical white matter) presented with greater impairment on
      memory/language tests vs executive control/visuoconstructive tests, a
      neuropsychological profile typically associated with Alzheimer disease. Patients
      with moderate WMA (mean LA = 12.76 +/- 2.49, approximately 25.6 to 38.1% of the
      subcortical white matter) presented with equal impairment on
      executive/visuoconstructional vs memory/language tests. Patients with severe WMA
      (mean LA = 21.76 +/- 2.97, approximately 46.9 to 62.4% of the subcortical white
      matter) displayed a profile of greater executive/visuoconstructional impairment
      relative to memory/language disabilities. CONCLUSION: A profile of equal
      impairment on tests of executive control and memory along with radiologic
      evidence involving about one-fourth of the cerebral white matter as measured by
      the Leukoaraiosis Scale may be sufficient for a diagnosis of subcortical vascular
      dementia.

PMID- 16087902
TI  - Effect of reproductive factors and postmenopausal hormone use on the risk of
      Parkinson disease.
AB  - OBJECTIVE: Parkinson disease (PD) is less common in women possibly because of
      hormonal or reproductive influences. The objective of this study was to evaluate
      the associations of reproductive factors and postmenopausal hormone use with the
      risk of PD among postmenopausal women. METHODS: Incident cases (n = 178) and
      randomly selected age-matched controls (n = 189) who were members of the Kaiser
      Permanente Medical Care Program (KPMCP) of Northern California participated in
      the study conducted during the years 1994 to 1995. Statistical analyses were
      carried out using logistic regression. RESULTS: The association of postmenopausal
      hormone use with PD risk depended on the type of menopause. Among women with
      history of a hysterectomy with or without an oophorectomy, estrogen use alone was
      associated with a 2.6-fold increased risk (adjusted odds ratio (OR) 2.6, 95% CI:
      1.1 to 6.1) and significant trends in the risk of PD were observed with
      increasing duration of estrogen use, but disease risk was not influenced by
      recency of use. In contrast, among women with natural menopause, no increased
      risk of PD was observed with hormone use (estrogen alone or a combined estrogen
      progestin regimen). Early age at final menstrual period (44 years or younger) was
      associated with reduction in risk (adjusted OR 0.5, 95% CI: 0.3 to 1.0). Age at
      menarche and parity were not associated with the risk of PD. CONCLUSION:
      Postmenopausal use of estrogen alone may increase the risk of Parkinson disease
      (PD) among women with a hysterectomy. Among women with natural menopause for whom
      the usual treatment is combined estrogen-progestin therapy, no increased risk of
      PD was observed.

PMID- 16087903
TI  - Blood harmane concentrations and dietary protein consumption in essential tremor.
AB  - BACKGROUND: Beta-carboline alkaloids (e.g., harmane) are highly tremorogenic
      chemicals. Animal protein (meat) is the major dietary source of these alkaloids.
      The authors previously demonstrated that blood harmane concentrations were
      elevated in patients with essential tremor (ET) vs controls. Whether this
      difference is due to greater animal protein consumption by patients or their
      failure to metabolize harmane is unknown. OBJECTIVE: The aim of this study was to
      determine whether patients with ET and controls differ with regard to 1) daily
      animal protein consumption and 2) the correlation between animal protein
      consumption and blood harmane concentration. METHODS: Data on current diet were
      collected with a semiquantitative food frequency questionnaire and daily calories
      and consumption of animal protein and other food types was calculated. Blood
      harmane concentrations were log-transformed (logHA). RESULTS: The mean logHA was
      higher in 106 patients than 161 controls (0.61 +/- 0.67 vs 0.43 +/- 0.72 g(
      10)/mL, p = 0.035). Patients and controls consumed similar amounts of animal
      protein (50.2 +/- 19.6 vs 49.4 +/- 19.1 g/day, p = 0.74) and other food types
      (animal fat, carbohydrates, vegetable fat) and had similar caloric intakes. In
      controls, logHA was correlated with daily consumption of animal protein (r =
      0.24, p = 0.003); in patients, there was no such correlation (r = -0.003, p =
      0.98). CONCLUSIONS: The similarity between patients and controls in daily animal
      protein consumption and the absence of the normal correlation between daily
      animal protein consumption and logHA in patients suggests that another factor
      (e.g., a metabolic defect) may be increasing blood harmane concentration in
      patients.

PMID- 16087904
TI  - Rate of progression differs in frontotemporal dementia and Alzheimer disease.
AB  - OBJECTIVE: To compare survival and rates of cognitive and functional decline in
      patients with autopsy-confirmed frontotemporal dementia (FTD) and Alzheimer
      disease (AD) in a large multicenter study. BACKGROUND: Despite advances in the
      clinical characterization of FTD, little is known about its rate of progression.
      Characterizing survival and rate of decline in FTD is important because it can
      provide prognostic guidelines and benchmarks to use in the evaluation of disease
      modifying drugs. METHODS: Seventy patients with FTD and 70 patients with AD who
      were followed by seven Alzheimer disease research centers until confirmation of
      diagnosis at autopsy were matched for overall age, education, and Mini-Mental
      State Examination (MMSE) score at initial evaluation. Survival and rates of
      cognitive and functional decline were compared. RESULTS: Patients with FTD had
      significantly shorter survival from initial evaluation to death than patients
      with AD (FTD = 4.2 years, AD = 6.0 years; log-rank test = 5.17, p < 0.05), and
      they declined significantly faster over one year on the MMSE (mean annual rate of
      change: -6.7 points for FTD vs -2.3 points for AD). A significantly greater
      proportion of patients with FTD were impaired in basic activities of daily living
      (ADLs) at initial evaluation, and lost the capacity for independent or minimally
      assisted ADLs over the subsequent year. CONCLUSIONS: The results are consistent
      with shorter survival and faster rates of cognitive and functional decline in
      patients with frontotemporal dementia (FTD) compared to those with Alzheimer
      disease (AD). This suggests that FTD follows a more malignant disease course than
      AD once dementia is clinically recognized.

PMID- 16087906
TI  - Cerebellar skew deviation and the torsional vestibuloocular reflex.
AB  - BACKGROUND: Skew deviation is typically caused by brainstem damage, and has not
      been identified with focal cerebellar lesions. This vertical strabismus has been
      attributed to asymmetric disruption of vestibuloocular reflex (VOR) projections
      from otolithic receptors of the utricle to ocular motoneurons, but asymmetry of
      the utriculo-ocular counter-roll reflex has not been detected. METHODS: Lesions
      localized to the cerebellum were identified by MRI in five patients with vertical
      strabismus. Their skew deviation was measured by prism cover tests in all
      patients and by search coils in three patients. The angular VOR was tested in
      patients and 10 controls during sinusoidal +/- 10 degree torsional, vertical, and
      horizontal head-on-body rotations at 0.5, 1, and 2 Hz. Static torsional VOR gain
      was measured by the change in torsional eye position divided by change in head
      position during maintained head tilt. RESULTS: Static torsional VOR gains were
      asymmetric in each patient. Three patterns of asymmetry were identified: 1)
      decreased static gain in one eye in both directions; 2) decreased gains in both
      eyes in one direction; and 3) asymmetric gain in one direction in one eye alone.
      Dynamic torsional VOR gains were symmetrically reduced in both directions in both
      eyes in all patients. CONCLUSIONS: Focal cerebellar lesions can cause skew
      deviation. The static torsional vestibuloocular reflex (VOR) is linked to
      cerebellar control of vertical vergence. Asymmetry between the eyes or in
      direction of the static torsional VOR provides evidence that monocular or
      binocular imbalance of the utriculo-ocular reflex leads to cerebellar skew
      deviation.

PMID- 16087905
TI  - Increased hippocampal activation in mild cognitive impairment compared to normal
      aging and AD.
AB  - OBJECTIVE: To use fMRI to investigate whether hippocampal and entorhinal
      activation during learning is altered in the earliest phase of mild cognitive
      impairment (MCI). METHODS: Three groups of older individuals were studied: 10
      cognitively intact controls, 9 individuals at the mild end of the spectrum of
      MCI, and 10 patients with probable Alzheimer disease (AD). Subjects performed a
      face-name associative encoding task during fMRI scanning, and were tested for
      recognition of stimuli afterward. Data were analyzed using a functional-anatomic
      method in which medial temporal lobe (MTL) regions of interest were identified
      from each individual's structural MRI, and fMRI activation was quantified within
      each region. RESULTS: Significantly greater hippocampal activation was present in
      the MCI group compared to controls; there were no differences between these two
      groups in hippocampal or entorhinal volumes. In contrast, the AD group showed
      hippocampal and entorhinal hypoactivation and atrophy in comparison to controls.
      The subjects with MCI performed similarly to controls on the fMRI recognition
      memory task; patients with AD exhibited poorer performance. Across all 29
      subjects, greater mean entorhinal activation was found in the subgroup of 13
      carriers of the APOE epsilon4 allele than in the 16 noncarriers. CONCLUSIONS: The
      authors hypothesize that there is a phase of increased medial temporal lobe
      activation early in the course of prodromal Alzheimer disease followed by a
      subsequent decrease as the disease progresses.

PMID- 16087907
TI  - Messenger RNA degradation may be inhibited in sporadic inclusion body myositis.
AB  - OBJECTIVE: To integrate an immune-mediated mechanism and the disturbed protein
      expression in sporadic inclusion body myositis (IBM). BACKGROUND: In IBM,
      abnormal fibers harbor inclusions of some proteins found in the brains of
      patients with Alzheimer disease (AD). Poly(A)-binding protein 1 (PABP1) is the
      RNA binding protein that attaches to the poly(A) tail of mRNA and is involved in
      translation and mRNA degradation. Under stresses, mRNA combined with PABP1 forms
      cytoplasmic granules called stress granules. METHODS: Using 12 muscle biopsies
      with sporadic IBM and 46 controls, the authors localized PABP1 by
      immunohistochemistry, and poly(A)-containing RNA (poly(A)+ RNA) using the in situ
      hybridization method. They also immuno-localized HuR, one of the components of
      stress granules. RESULTS: In IBM, a proportion of fibers, including those
      vacuolated, showed an abnormal accumulation of PABP1 immuno-positive deposits. An
      immunofluorescence study indicated that large PABP1 positive deposits formed
      conglomerates with poly(A)+ RNA and PABP1 colocalized with HuR. Although PABP1
      positive cytoplasmic inclusions were found in disease controls, their aggregates
      combined with poly(A)+ RNA were only detected in IBM. CONCLUSIONS: The
      localization of PABP1 positive deposits in inclusion body myositis (IBM) and
      other diseases may correspond to the stress granules that are formed under
      exposure to cellular stresses and the sites of mRNA turnover. The concomitant
      aggregation of poly(A)+ RNA that is specifically found in IBM may be due to the
      inhibition of mRNA degradation, which may affect translation. The authors
      speculate that an autoantibody against mRNA degradation machinery could play a
      role in this inhibition.

PMID- 16087908
TI  - Single-pulse electrical stimulation identifies epileptogenic frontal cortex in
      the human brain.
AB  - OBJECTIVE: To assess the value of single-pulse electrical stimulation (SPES) to
      identify frontal epileptogenic cortex during presurgical assessment. METHODS:
      SPES (1-millisecond pulses, 4 to 8 mA, 0.1 Hz) has been used during chronic
      recordings in 30 patients with intracranial electrodes in the frontal lobes. As a
      result of presurgical assessment, 17 patients were considered to have frontal
      epilepsy and 13 extrafrontal epilepsy. RESULTS: Two types of responses to SPES
      were seen: 1) early responses: starting immediately after the stimulus and
      considered as normal responses; 2) late responses: two types of responses seen in
      some areas after the initial early response: a) delayed responses: spikes or
      sharp waves occurring between 100 milliseconds and 1 second after stimulation.
      Frontal delayed responses were seen in 11 frontal patients and 1 extrafrontal
      patient, whereas extrafrontal delayed responses were seen in 1 frontal and 10
      extrafrontal patients. b) Repetitive responses: two or more consecutive sharp-and
      slow-wave complexes, each resembling the initial early response. Repetitive
      responses were seen only when stimulating the frontal lobes of 10 frontal
      patients. Among the 17 frontal patients, 13 had late responses exclusively in the
      epileptogenic frontal lobe, whereas only 3 showed them in both frontal lobes.
      Frontal late responses were associated with neuropathologic abnormalities, and
      complete resection of abnormal SPES areas was associated with good postsurgical
      seizure outcome. CONCLUSIONS: Single-pulse electrical stimulation (SPES) could be
      an important additional investigation during presurgical assessment to identify
      frontal epileptogenicity. SPES can be useful in patients who have widespread or
      multiple epileptogenic areas, normal neuroimaging, or few seizures during
      telemetry.

PMID- 16087909
TI  - Large thalamic mass due to neuro-Behcet disease.

PMID- 16087910
TI  - Individual differences in endogenous pain modulation as a risk factor for chronic
      pain.
AB  - This review summarizes evidence, primarily from recent human studies, indirectly
      supporting a novel hypothesis: that the assessment of healthy individuals'
      responses to standardized noxious stimuli in a controlled laboratory environment
      has important implications for the later risk of developing a broad spectrum of
      chronically painful conditions. Descriptions of many chronic pain syndromes note
      that the disorder (e.g., fibromyalgia, headache, complex regional pain syndrome)
      is associated with hypersensitivity to pain and with reduced endogenous
      inhibition of pain, implying that an individual's processing of pain-related
      information changes with the onset of the syndrome. However, pain sensitivity and
      pain-inhibitory capacity are normally distributed along a wide continuum in the
      general population, and recent evidence suggests that heightened baseline pain
      sensitivity and reduced basal pain-inhibitory processing place individuals at
      greater risk for experiencing severe, acute, clinical pain (e.g., postoperative
      pain). More controversial is the hypothesis that such individual-difference
      characteristics confer risk for, or protection against, chronic pain; although
      only a single prospective study has been published, substantial indirect evidence
      supports the contention that greater basal pain sensitivity and reduced pain
      inhibitory capacity may act as a diathesis for chronic pain. Long-term cohort
      studies are necessary to test this hypothesis; such research could yield insight
      into the nature of chronic pain and permit greater precision in selecting high
      risk individuals for chronic pain prevention research.

PMID- 16087911
TI  - A single dose of gabapentin reduces acute pain and allodynia in patients with
      herpes zoster.
AB  - This randomized, double-blind, placebo-controlled crossover study measured the
      effect of a single dose of oral gabapentin (900 mg) on pain and allodynia
      associated with herpes zoster. Pain severity decreased by 66% with gabapentin
      compared to 33% with placebo. Reductions in allodynia area and severity, and
      overall pain relief, were also greater with gabapentin.

PMID- 16087912
TI  - The chemokine CXCL13 (BLC): a putative diagnostic marker for neuroborreliosis.
AB  - Using protein expression profiling, the authors identified an upregulation of the
      chemokine B lymphocyte chemoattractant (BLC) in the CSF of patients with
      neuroborreliosis but not in patients with noninflammatory and various other
      inflammatory neurologic diseases. This upregulation was confirmed by ELISA,
      showing increased BLC levels in every neuroborreliosis patient while being
      undetectable in patients with noninflammatory neurologic diseases. These results
      point to BLC as a putative additional diagnostic marker for neuroborreliosis.

PMID- 16087913
TI  - Electrical impedance myography in the bedside assessment of inflammatory
      myopathy.
AB  - Electrical impedance myography (EIM) is a new technique with potential for the
      noninvasive bedside assessment of myopathy. EIM was performed on the quadriceps
      of 10 patients with inflammatory myopathy and 10 normal subjects. The major EIM
      parameter, the spatially averaged phase, was 35% lower in the myositis patients
      and correlated with whole-body (r = 0.765, p = 0.01) and quadriceps (r = 0.673, p
      = 0.03) strength.

PMID- 16087914
TI  - Mitochondrial DNA copy number threshold in mtDNA depletion myopathy.
AB  - The authors measured the absolute amount of mitochondrial DNA (mtDNA) within
      single muscle fibers from two patients with thymidine kinase 2 (TK2) deficiency
      and two healthy controls. TK2 deficient fibers containing more than 0.01
      mtDNA/microm3 had residual cytochrome c oxidase (COX) activity. This defines the
      minimum amount of wild-type mtDNA molecules required to maintain COX activity in
      skeletal muscle and provides an explanation for the mosaic histochemical pattern
      seen in patients with mtDNA depletion syndrome.

PMID- 16087915
TI  - Polyneuropathy associated with interferon beta treatment in patients with
      multiple sclerosis.
AB  - Peripheral neuropathy has been reported as a side effect of interferon alpha, but
      not with interferon beta (IFNbeta) treatment. The authors assessed six patients
      with multiple sclerosis who developed polyneuropathy, or had exacerbation of
      previously subclinical neuropathy, during treatment with IFNbeta. In five
      patients the neuropathy improved after discontinuation of treatment and in two
      patients it relapsed upon rechallenge.

PMID- 16087916
TI  - Reduced amplitude of the sural nerve sensory action potential in PARK2 patients.
AB  - The authors performed nerve conduction studies in nine PARK2 and eight idiopathic
      Parkinson disease patients and found a significant reduction of sural sensory
      nerve action potential (SNAP) amplitude in eight PARK2 patients who mostly
      remained asymptomatic. These data suggest that sensory axonal neuropathy may be a
      common clinical feature of PARK2 and a reduced amplitude of sural SNAP could be a
      diagnostic indicator of PARK2.

PMID- 16087917
TI  - An intronic base alteration of the CHRNE gene leading to a congenital myasthenic
      syndrome.
AB  - Reported is a patient with a congenital myasthenic syndrome due to two compound
      heterozygous mutations of the CHRNE gene. The molecular consequences of a novel
      intronic base alteration (CHRNE IVS5-16GA) remote from the splice acceptor site
      were investigated in vivo and in vitro. In conclusion, RNA analysis may be
      necessary to reveal unexpected splicing aberrations due to intronic mutations
      that are not part of the consensus splice site.

PMID- 16087918
TI  - Therapeutic trial of repetitive transcranial magnetic stimulation after acute
      ischemic stroke.
AB  - Repetitive transcranial magnetic stimulation (rTMS) or sham stimulation was given
      over the motor cortex daily for 10 days to two randomly assigned groups of 26
      patients with acute ischemic stroke. Patients otherwise continued their normal
      treatment. Disability scales measured before rTMS, at the end of the last rTMS
      session, and 10 days later showed that real rTMS improved patients' scores more
      than sham.

PMID- 16087919
TI  - Multiparametric MRI and ultrasound findings in patients with internal carotid
      artery dissection.
AB  - In this study, clinical, MRI, and ultrasound findings in 33 patients with 37 MRI
      confirmed internal carotid artery dissections (ICADs) were investigated. In 24 of
      37 (64.9%) diffusion-weighted MRI (DWI) revealed acute ischemic brain lesions.
      ICADs with subsequent DWI lesions usually had a concentric position of the mural
      hematoma (14 of 24; 58.3%). In contrast, ICADs without DWI lesions (13 of 37;
      35.1%) demonstrated an eccentric position of the mural hematoma (10 of 13;
      76.9%), sometimes without ultrasound abnormality (5 of 13; 38.5%), while
      nonischemic clinical signs were frequent (11 of 13; 84.6%). A hemodynamic stroke
      pattern with comparatively large ischemic lesions along the hemodynamic risk
      zones was noted in 7 of 24 patients (29.2%).

PMID- 16087920
TI  - Dopaminergic effects on encoding of a motor memory in chronic stroke.
AB  - The effects of a single oral dose of levodopa administered in a randomized,
      double-blind, placebo-controlled cross-over design on formation of a motor memory
      were studied by a training protocol in patients with chronic stroke. Levodopa
      enhanced the ability of motor training to encode an elementary motor memory
      relative to placebo. Up-regulation of dopaminergic function may enhance motor
      memory formation, crucial for successful rehabilitative treatments in patients
      with chronic stroke.

PMID- 16087921
TI  - Marchiafava-Bignami disease: diffusion-weighted MRI in corpus callosum and
      cortical lesions.
AB  - The clinical diagnosis of Marchiafava-Bignami disease (MBD) can be difficult.
      Acute demyelination of the corpus callosum is characteristic of the disease. The
      authors report the use of MR diffusion-weighted imaging (DWI) in six cases of
      acute MBD. They show that apparent diffusion coefficient restriction of the
      corpus callosum and cortical lesions were associated with a higher mortality rate
      and more severe cognitive sequelae.

PMID- 16087922
TI  - Frontotemporal dementia with ubiquitinated neuronal inclusions and visuospatial
      impairment.
AB  - Dementia with ubiquitinated neuronal inclusions has been described only with
      frontotemporal dementia (FTD). The authors report a patient with progressive FTD
      accompanied by prominent impairments in visuospatial cognitive functions.
      Pathology was characterized by ubiquitin-positive intranuclear and cytoplasmic
      neuronal inclusions. Cortical pathology was widespread and posteriorly
      accentuated but spared the hippocampal dentate gyrus.

PMID- 16087923
TI  - Delusions and hallucinations in dementia with Lewy bodies: worsening with
      memantine.
AB  - Three patients with probable dementia with Lewy bodies (DLB) experienced
      worsening delusions and visual hallucinations as a result of memantine therapy.
      Significant resolution occurred once treatment was discontinued. Caution is
      required when prescribing memantine to patients with possible DLB.

PMID- 16087924
TI  - Medical decision-making in neurodegenerative disease: mild AD and PD with
      cognitive impairment.
AB  - The authors compared medical decision-making capacity in patients with mild
      Alzheimer disease (AD), Parkinson disease (PD) with cognitive impairment, and
      older controls. Relative to controls and patients with PD, patients with AD were
      impaired on the consent ability of understanding the medical treatment situation
      and choices. Patients with PD were impaired on the consent ability of electing a
      treatment choice.

PMID- 16087925
TI  - Role of dynamic CT myelography in identifying the etiology of superficial
      siderosis.
AB  - The authors report three cases of superficial siderosis with a fluid-filled
      spinal canal cavity communicating with the subarachnoid space. The site of
      communication was identified with dynamic CT myelography and the defect was
      surgically repaired.

PMID- 16087926
TI  - Unusual neuroimaging in superficial siderosis.

PMID- 16087927
TI  - Vagal nerve stimulation effects on cerebellar tremor in multiple sclerosis.

PMID- 16087928
TI  - Neuroanatomy in monozygotic twins with Asperger disorder discordant for comorbid
      depression.

PMID- 16087929
TI  - A patient with left ventricular thrombus and recurrent stereotypic TIAs.

PMID- 16087930
TI  - Thalamic disequilibrium syndrome after thrombolytic therapy for acute myocardial
      infarction.

PMID- 16087931
TI  - Intrinsic epileptogenicity of an isolated periventricular nodular heterotopia.

PMID- 16087932
TI  - Charcot-Marie-Tooth with pyramidal signs is genetically heterogeneous: families
      with and without MFN2 mutations.

PMID- 16087934
TI  - Suicide after successful deep brain stimulation for movement disorders.

PMID- 16087935
TI  - Efficacy of rapid IV administration of valproic acid for status epilepticus.

PMID- 16087936
TI  - Should thrombolysis be given to a stroke patient refusing therapy due to profound
      anosognosia?

PMID- 16087937
TI  - Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized
      controlled trial.

PMID- 16087938
TI  - Depression and survival after hematopoietic stem cell transplantation: where do
      we go from here?

PMID- 16087939
TI  - Self-recognition and tumor response to immunotherapy.

PMID- 16087940
TI  - Optimal therapy for unresectable stage III non-small-cell lung cancer.

PMID- 16087941
TI  - Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally
      advanced non-small-cell lung cancer: a randomized phase II locally advanced multi
      modality protocol.
AB  - PURPOSE: This phase II noncomparative randomized trial was conducted to determine
      the optimal sequencing and integration of paclitaxel/carboplatin with standard
      daily thoracic radiation therapy (TRT), in patients with locally advanced
      unresected stage III non-small-cell lung cancer (NSCLC). Survival data were
      compared with historical standard sequential chemoradiotherapy data from the
      Radiation Therapy Oncology Group. PATIENTS AND METHODS: Patients with unresected
      stages IIIA and IIIB NSCLC, with Karnofsky performance status > or = 70% and
      weight loss < or = 10%, received two cycles of induction paclitaxel (200
      mg/m2)/carboplatin (area under the plasma concentration time curve [AUC] = 6)
      followed by TRT 63.0 Gy (arm 1, sequential) or two cycles of induction paclitaxel
      (200 mg/m2)/carboplatin (AUC = 6) followed by weekly paclitaxel (45
      mg/m2)/carboplatin (AUC = 2) with concurrent TRT 63.0 Gy (arm 2,
      induction/concurrent), or weekly paclitaxel (45 mg/m2)/carboplatin (AUC = 2)/TRT
      (63.0 Gy) followed by two cycles of paclitaxel (200 mg/m2)/carboplatin (AUC = 6;
      arm 3, concurrent/consolidation). RESULTS: With a median follow-up time of 39.6
      months, median overall survival was 13.0, 12.7, and 16.3 months for arms 1, 2,
      and 3, respectively. During induction chemotherapy, grade 3/4 granulocytopenia
      occurred in 32% and 38% of patients on study arms 1 and 2, respectively. The most
      common locoregional grade 3/4 toxicity during and after TRT was esophagitis,
      which was more pronounced with the administration of concurrent chemoradiotherapy
      on study arms 2 and 3 (19% and 28%, respectively). CONCLUSION: Concurrent weekly
      paclitaxel, carboplatin, and TRT followed by consolidation seems to be associated
      with the best outcome, although this schedule was associated with greater
      toxicity.

PMID- 16087942
TI  - Prognostic importance of preoperative CA-125 in International Federation of
      Gynecology and Obstetrics stage I epithelial ovarian cancer: an Australian
      multicenter study.
AB  - PURPOSE: To evaluate the prognostic significance of preoperative CA-125 levels on
      overall survival of patients with International Federation of Gynecology and
      Obstetrics (FIGO) stage I epithelial ovarian cancer (EOC). PATIENTS AND METHODS:
      Data from 518 patients with FIGO stage I EOC treated in seven gynecologic
      oncology centers throughout Australia between 1990 and 2002 were analyzed.
      Patients with borderline tumors and nonepithelial ovarian carcinomas were
      excluded, as were women in whom CA-125 had not been determined preoperatively.
      Preoperative CA-125 levels were studied in surgically staged and incompletely
      staged patients and compared with prognostic factors, such as substage, grade,
      and histologic type. Multivariate Cox models were calculated. RESULTS: CA-125
      levels more than 30 U/mL were associated with higher grade, substage 1B and 1C,
      nonmucinous histologic type, and older age. In univariate analysis, higher
      histologic grade, the absence of surgical staging, and preoperative CA-125 levels
      more than 30 U/mL were associated with impaired survival. Multivariate analysis
      identified histologic grade, preoperative CA-125, and surgical staging as
      independent predictors for survival. In the subgroup of completely surgically
      staged patients, the 5-year overall survival rate was 82% (95% CI, 76% to 88%)
      for patients with CA-125 levels more than 30 U/mL and 95% (95% CI, 90% to 99%)
      for patients with CA-125 levels of 30 U/mL or less (P = .028). In the group of
      incompletely staged patients, the 5-year survival rates were similar for patients
      with elevated and normal serum CA-125 levels. CONCLUSION: Complete surgical
      staging, histologic grade, and preoperative serum CA-125 levels are independent
      prognostic factors and should be included in the decision making for
      chemotherapy.

PMID- 16087943
TI  - Weekly paclitaxel improves pathologic complete remission in operable breast
      cancer when compared with paclitaxel once every 3 weeks.
AB  - PURPOSE: To determine the impact a change in schedule of paclitaxel
      administration from once every 3 weeks to frequent administration would have on
      the pathologic complete response (pCR) rate in the breast and lymph nodes for
      patients with invasive breast cancer treated with primary systemic chemotherapy
      (PST). PATIENTS AND METHODS: Patients with clinical stage I-IIIA breast cancer
      were randomly assigned to receive PST of paclitaxel doses administered either
      weekly (for a total of 12 doses of paclitaxel) or once every 3 weeks (four
      cycles), followed by four cycles of fluorouracil/doxorubicin/cyclophosphamide
      (FAC) in standard doses every 3 weeks. Two different doses of paclitaxel were
      used based on lymph node status defined by ultrasound and fine needle aspiration.
      Clinical response and extent of residual disease in the breast and lymph nodes
      was assessed after completion of all chemotherapy. RESULTS: A total of 258
      patients were randomly assigned to receive doses of paclitaxel administered
      either weekly or once every 3 weeks, followed by FAC. Of these 258 patients, 110
      patients had histologic lymph node involvement and 148 patients had clinical N0
      disease. Weekly paclitaxel followed by FAC was administered to 127 patients and
      once-every-3-weeks paclitaxel followed by FAC was administered to 131 patients.
      Clinical response to treatment was similar between groups (P = .25). Patients
      receiving weekly paclitaxel had a higher pCR rate (28.2%) than patients treated
      with once-every-3-weeks paclitaxel (15.7%; P = .02), with improved breast
      conservation rates (P = .05). CONCLUSION: The change in schedule of paclitaxel
      from once every 3 weeks to a more frequent administration significantly improved
      the ability to eradicate invasive cancer in the breast and lymph nodes.

PMID- 16087944
TI  - Autoimmunity correlates with tumor regression in patients with metastatic
      melanoma treated with anti-cytotoxic T-lymphocyte antigen-4.
AB  - PURPOSE: Previously, we reported our experience treating 14 patients with
      metastatic melanoma using a fully human antibody to cytotoxic T-lymphocyte
      antigen-4 (anti-CTLA-4) in conjunction with peptide vaccination. We have now
      treated 56 patients to evaluate two different dose schedules of anti-CTLA-4 and
      to explore the relationship between autoimmunity and tumor regression. PATIENTS
      AND METHODS: A total of 56 patients with progressive stage IV melanoma were
      enrolled onto the study. All had Karnofsky performance status > or = 60% with no
      prior history of autoimmunity. Twenty-nine patients received 3 mg/kg anti-CTLA-4
      every 3 weeks, whereas 27 received 3 mg/kg as their initial dose with subsequent
      doses reduced to 1 mg/kg every 3 weeks. In both cohorts patients received
      concomitant vaccination with two modified HLA-A*0201-restricted peptides from the
      gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-288(288V).
      RESULTS: Two patients achieved a complete response (ongoing at 30 and 31 months,
      respectively) and five patients achieved a partial response (durations of 4, 6,
      25+, 26+, and 34+ months, respectively), for an overall objective response rate
      of 13%. Tumor regression was seen in lung, liver, brain, lymph nodes, and
      subcutaneous sites. Of 14 patients with grade 3/4 autoimmune toxicity, five (36%)
      experienced a clinical response compared with only two responses in the 42
      patients (5%) with no autoimmune toxicity (P = .008). There were no significant
      differences in response rate or toxicity between the two dose schedules.
      CONCLUSION: Administration of anti-CTLA-4 monoclonal antibody plus peptide
      vaccination can cause durable objective responses, which correlate with the
      induction of autoimmunity, in patients with metastatic melanoma.

PMID- 16087945
TI  - Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic
      patients with metastatic breast cancer receiving first-line chemotherapy: a
      survival study.
AB  - PURPOSE: To evaluate the effect on survival and quality of life of maintaining
      hemoglobin (Hb) in the range of 12 to 14 g/dL with epoetin alfa versus placebo in
      women with metastatic breast cancer (MBC) receiving first-line chemotherapy.
      PATIENTS AND METHODS: Eligible patients were randomly assigned to receive epoetin
      alfa 40,000 U once weekly or placebo for 12 months. Study drug was initiated if
      baseline Hb was < or = 13 g/dL or when Hb decreased to < or = 13g/dL during the
      study. The primary end point was 12-month overall survival (OS). RESULTS: The
      study drug administration was stopped early in accordance with a recommendation
      from the Independent Data Monitoring Committee because of higher mortality in the
      group treated with epoetin alfa. Enrollment had been completed, with 939 patients
      enrolled (epoetin alfa, n = 469; placebo, n = 470). Most patients had Hb more
      than 12 g/dL at baseline (median Hb, 12.8 g/dL) or during the study. From the
      final analysis, 12-month OS was 70% for epoetin alfa recipients and 76% for
      placebo recipients (P = .01). Optimal tumor response and time to disease
      progression were similar between groups. The reason for the difference in
      mortality between groups could not be determined from additional subsequent
      analyses involving both study data and chart review. CONCLUSION: In this trial,
      the use of epoetin alfa to maintain high Hb targets in women with MBC, most of
      whom did not have anemia at the start of treatment, was associated with decreased
      survival. Additional research is required to clarify the potential impact of
      erythropoietic agents on survival when the Hb target range is 10 to 12 g/dL.

PMID- 16087946
TI  - Associations between drug metabolism genotype, chemotherapy pharmacokinetics, and
      overall survival in patients with breast cancer.
AB  - PURPOSE: To evaluate associations between patient survival, pharmacokinetics, and
      drug metabolism-related genetic polymorphisms in patients receiving a combination
      chemotherapy regimen for breast cancer. PATIENTS AND METHODS: A genotype
      association study was conducted on 85 chemotherapy-naive patients with metastatic
      or inflammatory breast cancer that were evaluated for an extended period after
      receiving standard-dose chemotherapy followed by high-dose cyclophosphamide,
      cisplatin, and carmustine. Blood pharmacokinetics were evaluated, and DNA was
      genotyped for 29 polymorphisms in 17 drug metabolism genes. RESULTS: Patients
      with cyclophosphamide plasma exposures above the median (implying slower
      metabolic activation) had a shorter survival than those below the median (1.8 v
      3.8 years, respectively; P = .042). Patients having a variant genotype of
      cytochrome P450 3A4 displayed higher blood concentrations of parent (inactive)
      cyclophosphamide with the second and third doses (P = .024 and .028,
      respectively) in addition to slower cyclophosphamide activation over the three
      doses (P = .031). Median survival for these patients was 1.3 years compared with
      2.7 years for those without the variant (P = .043). Similar results were observed
      for patients carrying a genetic variant of P450 3A5. Median survival for patients
      with deletions of glutathione-S-transferase M1 gene was 3.5 v 1.5 years for
      patients with one or both copies (P = .041). Patients with a polymorphism in a
      gene regulating metallothionein had lower platinum concentrations and shorter
      survival (P = .033). CONCLUSION: These data suggest that pretreatment evaluation
      of drug metabolism genes may explain some interindividual differences in both
      anticancer drug pharmacokinetics and response. The correlations found here may
      have implications for other commonly used anticancer drugs.

PMID- 16087947
TI  - Ovarian suppression for breast cancer: an effective treatment in search of a
      home.

PMID- 16087948
TI  - A process for measuring the quality of cancer care: the Quality Oncology Practice
      Initiative.
AB  - PURPOSE: The Quality Oncology Practice Initiative (QOPI) is a practice-based
      system of quality self-assessment sponsored by the participants and the American
      Society of Clinical Oncology (ASCO). The process of quality evaluation,
      development of the pilot questionnaire, and preliminary results are reported.
      METHODS: Physicians from seven oncology groups developed medical record
      abstraction measures based on practice guidelines and consensus-supported
      indicators of quality care. Each practice completed two rounds of records review
      and received practice and aggregate results. Mean frequencies of responses for
      each indicator were compared among practices. RESULTS: Participants universally,
      if informally, find QOPI helpful, and results show statistically significant
      variation among practices for several indicators, including assessing pain in
      patients close to death, documentation of informed consent for chemotherapy, and
      concordance with granulocytic and erythroid growth factor administration
      guidelines. Measures with universally high concordance include the use of
      serotonin antagonist antiemetics according to the ASCO guideline; the presence of
      a pathology report in the record; the use of chemotherapy flow sheets; and
      adherence to standard chemotherapy recommendations for patients with certain
      stages of breast, colon, and rectal cancer. Concordance with quality indicators
      significantly changed between survey rounds for several measures. CONCLUSION:
      Pilot results indicate that the QOPI process provides a rapid and objective
      measurement of practice quality that allows comparisons among practices and over
      time. It also provides a mechanism for measuring concordance with published
      guidelines. Most importantly, it provides a tool for practice self-examination
      that can promote excellence in cancer care.

PMID- 16087949
TI  - Role of depression as a predictor of mortality among cancer patients after stem
      cell transplantation.
AB  - PURPOSE: To determine the association between depression and survival among
      cancer patients at 1, 3, and 5 years after stem-cell transplantation (SCT).
      PATIENTS AND METHODS: This was a prospective cohort study of 199 hematologic
      cancer patients who survived longer than 90 days after SCT and who were recruited
      in a University-based hospital between July 1994 and August 1997. Patients
      received a psychiatric assessment at four consecutive time points during
      hospitalization for SCT, yielding a total of 781 interviews. Depression diagnoses
      were determined on the basis of the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition. RESULTS: Eighteen (9.0%) and 17 patients (8.5%) met
      criteria for major and minor depression, respectively. Multivariate Cox
      regression models found major depression to be predictive of higher 1-year
      (hazard ratio [HR], 2.59; 95% CI, 1.21 to 5.53; P = .014) and 3-year mortality
      (HR, 2.04; 95% CI, 1.03 to 4.02; P = .041) but not 5-year mortality (HR, 1.48;
      95% CI, 0.76 to 2.87; P = .249). Minor depression had no effect on any mortality
      outcome. Other multivariate significant predictors of higher mortality were
      higher regimen toxicity in the 1-, 3-, and 5-year models; older age and acute
      lymphoblastic leukemia in the 3- and 5-year models; chronic myelogenous leukemia
      in the 3-year model; and lower functional status and intermediate/higher risk
      status in the 5-year model. Use of peripheral-blood stem cells predicted lower
      mortality in the 5-year model. CONCLUSION: After adjusting for multiple factors,
      major depression predicted higher 1- and 3-year mortality among cancer patients
      after SCT, underscoring the importance of adequate diagnosis and treatment of
      major depression.

PMID- 16087951
TI  - Erythropoietin use in cancer patients: a matter of life and death?

PMID- 16087950
TI  - Chemoendocrine therapy for premenopausal women with axillary lymph node-positive,
      steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188).
AB  - PURPOSE: Chemotherapy, tamoxifen, and ovarian ablation/suppression (OA/OS) are
      effective adjuvant approaches for premenopausal, steroid hormone receptor
      positive breast cancer. The value of combined therapy has not been clearly
      established. PATIENTS AND METHODS: Premenopausal women with axillary lymph node
      positive, steroid hormone receptor-positive breast cancer (1,503 eligible
      patients) were randomly assigned to six cycles of cyclophosphamide, doxorubicin,
      and fluorouracil (CAF), CAF followed by 5 years of monthly goserelin (CAF-Z), or
      CAF followed by 5 years of monthly goserelin and daily tamoxifen (CAF-ZT). The
      primary end points were time to recurrence (TTR), disease-free survival (DFS),
      and overall survival (OS) for CAF-Z versus CAF, and CAF-ZT versus CAF-Z. RESULTS:
      With a median follow-up of 9.6 years, the addition of tamoxifen to CAF-Z improved
      TTR and DFS but not OS. There was no overall advantage for addition of goserelin
      to CAF. CONCLUSION: Addition of tamoxifen to CAF-Z improves outcome for
      premenopausal node-positive, receptor-positive breast cancer. The role of OA/OS
      alone or with other endocrine agents should be studied more intensely.

PMID- 16087952
TI  - Will future progress in non-small-cell lung cancer be step by step... or by leaps
      and bounds?

PMID- 16087953
TI  - Practice variation: the Achilles' heel in quality cancer care.

PMID- 16087954
TI  - "Will weekly work"? Seems to be so....

PMID- 16087955
TI  - CA-125 and early ovarian cancer: does this help the clinician or further muddy
      the water?

PMID- 16087956
TI  - Randomized phase III trial of sequential chemoradiotherapy compared with
      concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer:
      Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Francais de Pneumo
      Cancerologie NPC 95-01 Study.
AB  - PURPOSE: We conducted a phase III study to compare the survival impact of
      concurrent versus sequential treatment with radiotherapy (RT) and chemotherapy
      (CT) in unresectable stage III non-small-cell lung cancer (NSCLC). PATIENTS AND
      METHODS: Patients were randomly assigned to one of the two treatment arms. In the
      sequential arm, patients received induction CT with cisplatin (120 mg/m2) on days
      1, 29, and 57, and vinorelbine (30 mg/m2/wk) from day 1 to day 78, followed by
      thoracic RT at a dose of 66 Gy in 33 fractions (2 Gy per fraction and 5 fractions
      per week). In the concurrent arm, the same RT was started on day 1 with two
      concurrent cycles of cisplatin 20 mg/m2/d and etoposide 50 mg/m2/d (days 1 to 5
      and days 29 to 33); patients then received consolidation therapy with cisplatin
      80 mg/m2 on days 78 and 106 and vinorelbine 30 mg/m2/wk from days 78 to 127.
      RESULTS: Two hundred five patients were randomly assigned. Pretreatment
      characteristics were well balanced between the two arms. There were six toxic
      deaths in the sequential arm and 10 in the concurrent arm. Median survival was
      14.5 months in the sequential arm and 16.3 months in the concurrent arm (log-rank
      test P = .24). Two-, 3-, and 4-year survival rates were better in the concurrent
      arm (39%, 25%, and 21%, respectively) than in the sequential arm (26%, 19%, and
      14%, respectively). Esophageal toxicity was significantly more frequent in the
      concurrent arm than in the sequential arm (32% v 3%). CONCLUSION: Although not
      statistically significant, clinically important differences in the median, 2-, 3
      , and 4-year survival rates were observed, with a trend in favor of concurrent
      chemoradiation therapy, suggesting that is the optimal strategy for patients with
      locally advanced NSCLC.

PMID- 16087958
TI  - Female androgen deficiency syndrome--an unproven hypothesis.

PMID- 16087957
TI  - Differential gene expression in ovarian tumors reveals Dusp 4 and Serpina 5 as
      key regulators for benign behavior of serous borderline tumors.
AB  - PURPOSE: Ovarian serous borderline tumors (SBT) are characterized by arborizing
      papillae lined by stratified epithelial cells, varying atypia, and absence of
      stromal invasion. Originally, these tumors have been classified as borderline
      because they behaved in a remarkably indolent manner, even with widespread tumor
      deposits called implants and the presence of lymph node involvement. The
      molecular biology of these lesions has just begun to be explored. High prevalence
      of B-RAF/K-RAS mutations in SBTs in contrast to serous carcinomas (SCAs)
      indicates that the mitogenic RAS-RAF-MEK-ERK-MAP kinase pathway is crucial for
      the pathogenesis of SBTs. The purpose of this study was to further unravel the
      genetic pathways through which SBTs develop, with a special focus on explaining
      the generally benign SBT behavior. MATERIALS AND METHODS: We generated RNA
      expression profiles of 38 ovarian serous neoplasms. Global Test pathway analysis
      and significance analysis of microarrays (SAM) of the expression profiles was
      performed. RESULTS: SAM and Global Testing showed that although the mitogenic
      pathway is activated in SBTs, activation of downstream genes involved in
      extracellular matrix (ECM) degradation is absent, suggesting an uncoupling of
      both events. In addition, we show that two genes involved in regulating this
      uncoupling, ERK-inhibitor Dusp 4 and uPA-inhibitor Serpina 5, are downregulated
      in SCAs in contrast to SBTs. In SCAs, this was associated with downstream MMP-9
      activation at both mRNA and protein level. CONCLUSION: We propose that the
      putative tumor suppressor genes Dusp 4 and Serpina 5 provide a major clue to the
      indolent behavior of SBTs.

PMID- 16087959
TI  - On the term "relative adrenal insufficiency"--or what do we really measure with
      adrenal stimulation tests?

PMID- 16087960
TI  - Cryptorchidism--an estrogen spoil?

PMID- 16087961
TI  - Letter re: FSH receptor polymorphisms and iatrogenic ovarian hyperstimulation.

PMID- 16087962
TI  - Letter re: Endogenous sex hormones and metabolic syndrome in aging men.

PMID- 16087963
TI  - Letter re: Persistent hypocalciuric effect of potassium bicarbonate in
      postmenopausal women.

PMID- 16087964
TI  - Letter re: Monitoring the response to treatment in acromegaly.

PMID- 16087965
TI  - Letter re: HPA axis testing after pituitary surgery.

PMID- 16087966
TI  - Letter re: Inflammation and lipoprotein changes with protracted exercise.

PMID- 16087967
TI  - Response of the American Journal of Clinical Nutrition to the National Institutes
      of Health Public Access Policy.

PMID- 16087968
TI  - The insulin-like growth factor axis: a potential link between glycemic index and
      cancer.

PMID- 16087969
TI  - Science-based micronutrient fortification: which nutrients, how much, and how to
      know?

PMID- 16087970
TI  - Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required
      for development of normal brain function? An overview of evidence from cognitive
      and behavioral tests in humans and animals.
AB  - This review is part of a series intended for nonspecialists that will summarize
      evidence relevant to the question of whether causal relations exist between
      micronutrient deficiencies and brain function. Here, we focus on experiments that
      used cognitive or behavioral tests as outcome measures in experimental designs
      that were known to or were likely to result in altered brain concentrations of
      the n-3 fatty acid docosahexaenoic acid (DHA) during the perinatal period of
      "brain growth spurt." Experimental designs reviewed include observational
      breastfeeding studies and randomized controlled trials in humans and studies in
      rodents and nonhuman primates. This review is based on a large number of expert
      reviews and commentaries and on some 50 recent studies in humans and animals that
      have not yet been included in published reviews. Expert opinion regarding the
      strengths and weaknesses of the major experimental systems and uncertainties
      associated with interpreting results is summarized. On the basis of our reading
      of this literature, we conclude that evidence from several types of studies,
      particularly studies in animals, suggests that, within the context of specific
      experimental designs, changes in brain concentrations of DHA are positively
      associated with changes in cognitive or behavioral performance. Additional
      experimental information required to conclude that a causal association exists is
      discussed, as are uncertainties associated with applying results from specific
      experimental designs to the question of whether infant formula should be
      supplemented with DHA.

PMID- 16087971
TI  - Eating behavior among women with anorexia nervosa.
AB  - BACKGROUND: Disturbed eating and severe caloric restriction are characteristic
      features of patients with anorexia nervosa (AN). Despite the importance of eating
      behavior in the presentation of AN, there have been relatively few objective
      laboratory studies of eating behavior among persons with eating disorders.
      OBJECTIVE: The purpose of the study was to obtain objective measures of eating
      behavior among patients with AN before and immediately after weight restoration
      and to compare those measures with measures among control subjects. DESIGN:
      Twelve patients hospitalized for AN and 12 control subjects participated in the
      study. Eleven of the 12 patients were retested at 90% of ideal body weight.
      RESULTS: The average meal consumption was 103.97 +/- 102.08 g for patients at low
      weight and 178.03 +/- 202.97 g after weight restoration (NS). Control subjects
      consumed significantly more than did AN patients at both time points, and the
      average meal size was 489.58 +/- 187.64 g. Patients showed significant decreases
      in psychological and eating-disordered symptoms after weight restoration.
      CONCLUSION: These data suggest that patients with AN show a persistent
      disturbance in eating behavior, despite the restoration of body weight and
      significant improvements in eating-disordered and psychological symptoms.

PMID- 16087972
TI  - Energy intakes of children after preloads: adjustment, not compensation.
AB  - BACKGROUND: Young children accurately compensate for energy-dense preloads
      consumed before test meals. The accuracy of compensation seems to deteriorate as
      a function of age. OBJECTIVE: The hypothesis that accurate energy compensation
      varies by age, body mass index, and individual characteristics of children and
      their mothers was tested. DESIGN: Energy intake (EI) from a test meal was
      measured in 74 children aged 6-9 y 90 min after the ingestion of no-energy (NE),
      low-energy (LE), or high-energy (HE) preload snacks. The NE preload consisted of
      250 mL water, the LE preload consisted of a 56-g muffin + a 250-mL orange drink
      (783 kJ), and the HE preload consisted of a 56-g muffin + a 250-mL orange drink
      (1628 kJ). RESULTS: A significant dose-related reduction in EI was found after
      the preloads; younger children adjusted more effectively than did older children,
      although total EI (including preload energy) indicated that the adjustment was
      not accurate. The compensation index (COMPX) differed by preload and age group;
      COMPX scores were higher between the NE and LE preloads (younger children: 44.4
      +/- 9.3%; older children: 57.0 +/- 11.6%) than between the NE and HE preloads
      (39.6 +/- 4.9%; 31.3 +/- 6.2%) and the LE and HE preloads (35.2 +/- 7.8%; 7.4 +/-
      9.8%). This finding indicates a more consistent response across preloads and a
      greater sensitivity to energy load by younger than by older children. High
      interindividual variation and low intraindividual variation in COMPX was found.
      The tendency to over- or undereat in response to the preloads (deviation from
      perfect) correlated directly and positively with maternal concerns about child
      overweight, not with actual BMI. CONCLUSIONS: The children adjusted their EIs in
      response to different preloads, and the younger children did so more effectively
      than did the older children. Poor short-term energy compensation may constitute a
      behavioral marker for positive energy balance.

PMID- 16087973
TI  - Lack of effect of dietary conjugated linoleic acids naturally incorporated into
      butter on the lipid profile and body composition of overweight and obese men.
AB  - BACKGROUND: Dietary conjugated linoleic acid (CLA) is known to reduce
      atherosclerosis, plasma total and LDL-cholesterol concentrations, and body fat
      accumulation in several animal species. Of the few studies that investigated the
      effects of CLA supplementation in humans, all used commercially formulated oral
      supplements made from a mixture of CLA isomers. OBJECTIVE: We compared the
      effects on plasma lipoproteins and body composition of the consumption of a
      modified butter naturally enriched with CLA (CLA-B: 4.22 g CLA/100 g butter fat)
      by the addition of sunflower oil to the diet of dairy cows with the consumption
      of a control butter (CON-B) that was low in CLA (0.38 g CLA/100 g butter fat).
      DESIGN: In a crossover design study including an 8-wk washout period, 16 men [x
      +/- SD age: 36.6 +/- 12.4 y; body mass index (in kg/m2): 31.2 +/- 4.4] were fed
      each of the 2 experimental isoenergetic diets, providing 15% of energy as
      protein, 45% as carbohydrates, and 40% as lipids, of which >60% was derived from
      experimental fats, for 4 wk. RESULTS: Consumption of the CLA-B diet induced a
      significantly (P < 0.05) smaller reduction in plasma total cholesterol and in the
      ratio of total to HDL cholesterol (-0.02 mmol/L and -0.00, respectively) than did
      consumption of the CON-B diet (-0.26 mmol/L and-0.34, respectively). Abdominal
      adipose tissue area measured by computed tomography showed no difference in
      accumulation of either visceral or subcutaneous adipose tissue after the 2
      experimental diets. CONCLUSION: These results suggest that a 10-fold CLA
      enrichment of butter fat does not induce beneficial metabolic effects in
      overweight or obese men.

PMID- 16087975
TI  - Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating,
      vegetarian, and vegan men.
AB  - BACKGROUND: Plasma concentrations of long-chain n-3 polyunsaturated fatty acids
      are lower in vegetarians and in vegans than in omnivores. No data are available
      on whether these concentrations differ between long- and short-term vegetarians
      and vegans. OBJECTIVES: We compared plasma fatty acid composition in meat-eaters,
      vegetarians, and vegans and examined whether the proportions of eicosapentaenoic
      acid (20:5n-3; EPA), docosapentaenoic acid (22:5n-3; DPA), and docosahexaenoic
      acid (22:6n-3; DHA) were related to the subjects' duration of adherence to their
      diets or to the proportions of plasma linoleic acid (18:2n-6; LA) and alpha
      linolenic acid (18:3n-3; ALA). DESIGN: The present cross-sectional study included
      196 meat-eating, 231 vegetarian, and 232 vegan men in the United Kingdom.
      Information on anthropometry, diet, and smoking habits was obtained through a
      questionnaire. Total fatty acid composition in plasma was measured. RESULTS: The
      proportions of plasma EPA and DHA were lower in the vegetarians and in the vegans
      than in the meat-eaters, whereas only small differences were seen for DPA. Plasma
      EPA, DPA, and DHA proportions were not significantly associated with the duration
      of time since the subjects became vegetarian or vegan, which ranged from <1 y to
      >20 y. In the vegetarians and the vegans, plasma DHA was inversely correlated
      with plasma LA. CONCLUSIONS: The proportions of plasma long-chain n-3 fatty acids
      were not significantly affected by the duration of adherence to a vegetarian or
      vegan diet. This finding suggests that when animal foods are wholly excluded from
      the diet, the endogenous production of EPA and DHA results in low but stable
      plasma concentrations of these fatty acids.

PMID- 16087974
TI  - Increasing dietary palmitic acid decreases fat oxidation and daily energy
      expenditure.
AB  - BACKGROUND: Oleic acid (OA) is oxidized more rapidly than is palmitic acid (PA).
      OBJECTIVE: We hypothesized that changing the dietary intakes of PA and OA would
      affect fatty acid oxidation and energy expenditure. DESIGN: A double-masked trial
      was conducted in 43 healthy young adults, who, after a 28-d, baseline, solid-food
      diet (41% of energy as fat, 8.4% as PA, and 13.1% as OA), were randomly assigned
      to one of two 28-d formula diets: high PA (40% of energy as fat, 16.8% as PA, and
      16.4% as OA; n = 21) or high OA (40% of energy as fat, 1.7% as PA, and 31.4% as
      OA; n = 22). Differences in the change from baseline were evaluated by analysis
      of covariance. RESULTS: In the fed state, the respiratory quotient was lower (P =
      0.01) with the high OA (0.86 +/- 0.01) than with the high-PA (0.89 +/- 0.01)
      diet, and the rate of fat oxidation was higher (P = 0.03) with the high-OA
      (0.0008 +/- 0.0001) than with the high-PA (0.0005 +/- 0.0001 mg . kg fat-free
      mass(-1) . min(-1)) diet. Resting energy expenditure in the fed and fasting
      states was not significantly different between groups. Change in daily energy
      expenditure in the high-OA group (9 +/- 60 kcal/d) was significantly different
      from that in the high-PA group (-214 +/- 69 kcal/d; P = 0.02 or 0.04 when
      expressed per fat-free mass). CONCLUSIONS: Increases in dietary PA decrease fat
      oxidation and daily energy expenditure, whereas decreases in PA and increases in
      OA had the opposite effect. Increases in dietary PA may increase the risk of
      obesity and insulin resistance.

PMID- 16087976
TI  - A proinflammatory state is associated with hyperhomocysteinemia in the elderly.
AB  - BACKGROUND: The mechanism by which high circulating homocysteine concentrations
      are a risk factor for atherothrombosis is incompletely understood. A
      proinflammatory state is related to atherosclerosis, and recent studies suggest
      that acute phase reactants correlate with circulating concentrations of
      homocysteine. OBJECTIVE: We determined whether high concentrations of
      inflammatory markers are associated with hyperhomocysteinemia independently of
      dietary vitamin intakes, vitamin concentrations, and cardiovascular disease risk
      factors in a large, representative sample of the general population. DESIGN: Five
      hundred eighty-six men and 734 women were randomly selected from the inhabitants
      of 2 small towns near Florence, Italy. RESULTS: After adjustment for multiple
      potential confounders, interleukin 1 receptor antagonist (IL-1ra) and interleukin
      6 (IL-6) concentrations were significantly (P < 0.001) associated with plasma
      homocysteine concentrations in older (>65 y) populations. Compared with
      participants in the lowest IL-6 tertile, those in the highest tertile had a
      higher risk of having homocysteine concentrations that were high (>30 micromol/L;
      odds ratio: 2.6; 95% CI: 1.1, 5.6; P = 0.024) or in the intermediate range 15-30
      micromol/L (odds ratio: 1.6; 95% CI: 1.2, 2.2; P = 0.0014). Sedentary state,
      intakes of vitamin B-6 and folic acid, and serum folate, vitamin B-12, vitamin B
      6, and alpha-tocopherol concentrations were significant independent correlates of
      homocysteine. CONCLUSIONS: High circulating concentrations of IL-1ra and IL-6 are
      independent correlates of hyperhomocysteinemia and may explain, at least in part,
      the association between homocysteine and atherosclerosis.

PMID- 16087977
TI  - Inflammation contributes to low plasma amino acid concentrations in patients with
      chronic kidney disease.
AB  - BACKGROUND: Inflammation and malnutrition are common in chronic kidney disease
      (CKD) patients, and plasma concentrations of free amino acids (AAs) in these
      patients are often abnormal. Malnutrition contributes to alterations in AA
      concentrations. OBJECTIVE: The objective was to study the effects of inflammation
      on plasma AA concentrations. DESIGN: Concentrations of plasma AAs, serum albumin,
      and several inflammatory markers were analyzed in 200 fasting, nondiabetic CKD
      patients who were close to the start of renal replacement therapy. The
      nutritional status of these patients was assessed by a subjective global
      assessment. RESULTS: The patients with inflammation [C-reactive protein (CRP)
      concentrations >10 mg/L] or malnutrition had lower AA concentrations than did the
      patients with no inflammation or malnutrition. The presence of both inflammation
      and malnutrition was associated with more marked reductions in AA concentrations
      than was malnutrition alone. Significant inverse correlations were observed
      between the plasma concentrations of most of the essential and nonessential AAs
      and inflammatory markers, whereas serum albumin concentrations were positively
      correlated with several AA concentrations. A stepwise multivariate regression
      analysis showed that serum CRP concentrations were independently associated with
      low concentrations of the sums of both nonessential AAs and all AAs. An analysis
      of all-cause mortality with a Kaplan-Meier test showed that the patients with
      higher AA concentrations had significantly better survival than did the patients
      with lower AA concentrations. CONCLUSIONS: Plasma AA concentrations are low in
      CKD patients with inflammation and are inversely correlated with concentrations
      of inflammatory markers. Although inflammation and malnutrition are closely
      related, CRP concentrations were independently associated with low concentrations
      of the sums of both nonessential AAs and all AAs, which suggests an independent
      role of inflammation as a cause of low plasma AA concentrations in CKD patients.

PMID- 16087978
TI  - The glycemic index of foods influences postprandial insulin-like growth factor
      binding protein responses in lean young subjects.
AB  - BACKGROUND: Growth in normal and malignant tissues has been linked to
      hyperinsulinemia and insulin-like growth factors (IGFs). We hypothesized that IGF
      and IGF-binding protein (IGFBP) responses may be acutely affected by differences
      in the glycemic index (GI) of foods. OBJECTIVE: We compared the postprandial
      responses of IGFs and IGFBP to 2 foods of similar macronutrient composition but
      with greatly different GIs-pearled barley (GI: 25) and instant mashed potato (GI:
      85). DESIGN: Ten young lean subjects consumed 50-g carbohydrate portions of the 2
      foods or water (extended fast) in random order after an overnight fast. Capillary
      blood was collected at regular intervals over 4 h for measurement of blood
      glucose, insulin, and components of the IGF system. RESULTS: Serum IGFBP-1
      declined markedly after both meals, but the mean (+/-SEM) change at 4 h was
      significantly (P < 0.01) more prolonged after the low-GI meal (-55 +/- 20 ng/mL)
      than after the high-GI meal (-13 +/- 15 ng/mL). Conversely, the change in serum
      IGFBP-3 concentration at 4 h was significantly (P < 0.05) higher after the low-GI
      meal (251 +/- 102 ng/mL) than after the high-GI meal (-110 +/- 96 ng/mL); the
      same pattern was observed at 2 h. Changes in IGFBP-2, free IGF-1, and total IGF-1
      responses were minimal and did not differ significantly from those during the 4-h
      fast. CONCLUSION: Acute changes in IGFBP-3 after low-GI and high-GI foods may
      provide a biologic mechanism linking cell multiplication with greater consumption
      of high-GI carbohydrates.

PMID- 16087979
TI  - Whole-body protein anabolic response is resistant to the action of insulin in
      obese women.
AB  - BACKGROUND: Obesity is associated with insulin resistance of glucose and lipid
      metabolism. OBJECTIVE: We sought to determine the effects of obesity on the
      insulin sensitivity of protein metabolism. DESIGN: Whole-body [(13)C]leucine and
      [(3)H]glucose kinetics were measured in 9 lean and 10 obese women in the
      postabsorptive state and during a hyperinsulinemic, euglycemic, isoaminoacidemic
      clamp. RESULTS: In the postabsorptive state, the leucine endogenous rate of
      appearance (catabolism), normalized for fat-free mass, was 11% greater and the
      nonoxidative rate of disappearance (synthesis) was 8% greater in the obese than
      in the lean women, but net balance was 29% more negative (P < 0.05). Clamp amino
      acid and glucose infusion rates were significantly lower in the obese women than
      in the lean women (0.65 +/- 0.02 compared with 0.85 +/- 0.04 and 5.7 +/- 0.3
      compared with 9.1 +/- 0.5 mg x kg fat-free mass(-1) x min(-1), respectively; P <
      0.0001 for both), and their rates correlated positively (r = 0.635, P = 0.005).
      During hyperinsulinemia, synthesis was stimulated less and net leucine balance
      was much lower in the obese women than in the lean women (-0.08 +/- 0.06 and 0.30
      +/- 0.03 mumol x kg fat-free mass(-1) x min(-1), respectively; P < 0.0001). The
      percentage change in net leucine balance correlated negatively with all adiposity
      indexes. Plasma free fatty acids were less suppressed and the respiratory
      quotient was lower in the obese women than in the lean women. CONCLUSION: Obese
      women show a blunted protein anabolic response to hyperinsulinemia that is
      consistent with resistance to the action of insulin on protein concurrent with
      that on glucose and lipid metabolism.

PMID- 16087980
TI  - Altered interorgan response to feeding in patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Previously, we reported increased values for whole-body protein
      turnover in patients with chronic obstructive pulmonary disease (COPD) in the
      postabsorptive state. OBJECTIVE: The objective was to investigate whether intake
      of a carbohydrate-protein meal influences whole-body protein turnover differently
      in COPD patients and control subjects. DESIGN: Eight normal-weight patients with
      moderate COPD and 8 healthy control subjects were examined in the postabsorptive
      state and after 2 h of repeatedly ingesting a maltodextrin casein-based protein
      meal (0.02 g x kg body wt(-1) x 20 min(-1)). Combined simultaneous, continuous,
      intravenous infusion of L-[ring-2H5]-phenylalanine and L-[ring-2H2]-tyrosine
      tracer and oral repeated ingestion of 1-13C-phenylalanine were performed to
      measure whole-body protein synthesis (WbPS) and first-pass splanchnic extraction
      of phenylalanine. Endogenous rate of appearance of phenylalanine as the measure
      of whole-body protein breakdown (WbPB) and netWbPS was calculated as WbPS--WbPB.
      Arterialized venous blood was sampled for amino acid enrichment and concentration
      analyses. RESULTS: Feeding induced an increase in WbPS and a reduction in WbPB.
      The reduction in WbPB was larger in the COPD group than in the control group (P <
      0.05) and was related to the lower splanchnic extraction of phenylalanine in the
      patients. Consequently, netWbPS increased more after feeding in the COPD group
      than in the control group (P < 0.05). CONCLUSION: Feeding induces more protein
      anabolism in normal-weight patients with moderate COPD than in healthy control
      subjects. This is probably because these COPD patients are characterized by an
      adaptive interorgan response to feeding to prevent or delay weight loss at this
      disease stage.

PMID- 16087981
TI  - The daily valine requirement of healthy adult Indians determined by the 24-h
      indicator amino acid balance approach.
AB  - BACKGROUND: The 1985 FAO/WHO/UNU requirement for valine was set at 10 mg x kg(-1)
      x d(-1) on the basis of nitrogen balance studies carried out in Western subjects.
      It is likely that the requirement is higher, however, because the requirement of
      another branched-chain amino acid, leucine, was found to be about 3 times as high
      (40 mg x kg(-1) x d(-1)) as the 1985 FAO/WHO/UNU value (14 mg x kg(-1) x d(-1)).
      OBJECTIVE: We assessed the valine requirement in healthy, well-nourished Indians
      by using 7 test valine intakes (5, 10, 15, 20, 25, 30, and 35 mg x kg(-1) x d(
      1)) and the 24-h indicator amino acid oxidation (24-h IAAO) and balance (24-h
      IAAB) method, with phenylalanine as the indicator amino acid, while maintaining
      leucine intake at 40 mg x kg(-1) x d(-1). DESIGN: Eighteen healthy, well
      nourished Indian men were studied during each of 3 randomly assigned 7-d diet
      periods supplying valine intakes that were equally placed on either side of a
      putative mean valine requirement of 20 mg x kg(-1) x d(-1). Twenty-four-hour IAAO
      and 24-h IAAB were measured on day 7 by use of a 24-h [13C]phenylalanine tracer
      infusion. The breakpoint in the relation between these values and the valine
      intake was determined. RESULTS: Two-phase linear regression of daily
      phenylalanine oxidation or balance against valine intake estimated a breakpoint
      in the response curve at a valine intake of 17 mg x kg(-1) x d(-1) (95% Fieller's
      CI: 11, > 35 and 11, 28 mg x kg(-1) x d(-1), respectively). CONCLUSION: From the
      24-h IAAO/IAAB approach, a mean valine requirement of 17 mg x kg(-1) x d(-1) is
      proposed for healthy, well-nourished Indian adults.

PMID- 16087982
TI  - Only a small proportion of anemia in northeast Thai schoolchildren is associated
      with iron deficiency.
AB  - BACKGROUND: Iron deficiency is assumed to be the major cause of anemia in
      northeast Thailand, but other factors may be involved. OBJECTIVE: We determined
      the prevalence of anemia among schoolchildren in northeast Thailand and the role
      of hemoglobinopathies, selected micronutrient deficiencies, and other factors in
      hemoglobin status. DESIGN: Blood samples were collected from 567 children aged 6
      12.9 y attending 10 primary schools for the determination of a complete blood
      count and hemoglobin type [Hb AA (normal hemoglobin), Hb AE (heterozygous for Hb
      type E), and Hb EE (homozygous for Hb type E)] and the measurement of serum
      ferritin, transferrin receptor, retinol, vitamin B-12, and plasma and erythrocyte
      folate concentrations. Children with a C-reactive protein concentration > or = 10
      mg/L (n = 12), which indicated infection, were excluded. RESULTS: The prevalence
      of anemia was 31%. Age, hemoglobin type, and serum retinol were the major
      predictors of hemoglobin concentration. Hb AA and Hb AE children with anemia had
      lower (P < 0.01) hematocrit, mean cell volume, and serum retinol values than did
      their nonanemic counterparts; no significant differences in serum ferritin were
      found by hemoglobin type. Only 16% (n = 22) of the anemic Hb AA and Hb AE
      children were iron deficient. Hb AA and Hb AE children with a serum retinol
      concentration <0.70 micromol/L (n = 14) had a significantly higher geometric mean
      serum ferritin concentration than did those with a retinol concentration > or =
      0.70 micromol/L (P = 0.009); no significant difference in transferrin receptor
      concentrations was found between these 2 groups. CONCLUSIONS: Hemoglobinopathies,
      suboptimal vitamin A status, and age were the major predictors of hemoglobin
      concentration. The contribution of iron deficiency to anemia was low, and its
      detection was complicated by coexisting suboptimal vitamin A status.

PMID- 16087983
TI  - Increasing the iodine concentration in the Swiss iodized salt program markedly
      improved iodine status in pregnant women and children: a 5-y prospective national
      study.
AB  - BACKGROUND: Many industrialized countries struggle to maintain adequate iodine
      intake because of changes in dietary habits and the food supply. In Switzerland,
      because of declining iodine intakes in children and pregnant women, the iodine
      concentration in table salt was increased from 15 to 20 mg/kg. OBJECTIVE: We
      evaluated Swiss iodine nutrition after the 1999 increase in the salt iodine
      concentration. DESIGN: In 1999 and 2004, a 3-stage probability proportionate-to
      size cluster sampling was done to obtain a representative national sample of
      primary schoolchildren and pregnant women. Urine and household salt were
      collected for iodine measurement. The frequency of elevated thyrotropin
      concentrations found in the newborn screening program was evaluated before and
      after the increase. RESULTS: In 1999, median urinary iodine (UI) concentrations
      among children (n = 610) and pregnant women (n = 511) were 115 microg/L (range: 5
      413 microg/L) and 138 microg/L (range: 5-1881 microg/L), respectively, which
      indicated marginal iodine status. In 2004, median UI concentrations among
      children (n = 386) and pregnant women (n = 279) were 141 microg/L (range: 0-516
      microg/L) and 249 microg/L (range: 8-995 microg/L), respectively (P < 0.01).
      Newborn thyrotropin concentrations >5 mU/L decreased from 2.9% in 1992-1998 (n =
      259 035) to 1.7% in 1999-2004 (n = 218 665) (P < 0.0001). CONCLUSIONS: A 25%
      increase in iodine concentration in iodized table salt markedly improved iodine
      status in Switzerland, which showed the value of monitoring and adjusting iodine
      concentrations in national salt programs. The frequency of newborn thyrotropin
      concentrations >5 mU/L appears to be a sensitive indicator of iodine nutrition
      during pregnancy.

PMID- 16087984
TI  - Association of maternal smoking with overweight at age 3 y in American Indian
      children.
AB  - BACKGROUND: Prevalence rates of overweight are higher among American Indian
      children than among any other ethnic group, but little research has explored
      contributing influences. OBJECTIVE: The objective was to determine the prevalence
      and predictors of body mass index (BMI; in kg/m2) > or = 85th percentile in
      American Indian children in Wisconsin. DESIGN: A retrospective analysis was
      conducted with linked pediatric and pregnancy nutrition surveillance systems and
      birth records from 1997 through 2001. Participants were American Indian mothers
      and children (aged 0-3 y) who were participating in the Special Supplemental
      Nutrition Program for Women, Infants, and Children in Wisconsin. Outcome
      measurements included indicators of BMI > or = 85th percentile identified by
      using binary logistic regression. RESULTS: Of the 3-y-olds, 22.2% were overweight
      and 18.7% were at risk of overweight. Of their mothers, 42.5% had smoked during
      pregnancy. Smoking at the initial prenatal visit significantly predicted
      overweight and risk of overweight in children at age 3 y (odds ratio: 2.16; 95%
      CI: 1.05, 4.47). Despite being smaller at birth, the children of smoking mothers
      had a significantly (P < 0.05) greater increase in weight-for-length z score
      between birth and age 3 y than did children of nonsmokers. This greater increase
      was due to a significantly (P < 0.02) greater increase in weight in children of
      smokers than in those of nonsmokers and not to a relatively slower increase in
      height. CONCLUSIONS: Our findings suggest the early influence of maternal smoking
      on the prevalence of overweight at age 3 y in a high-risk American Indian
      population and provide evidence that interventions to reduce smoking in pregnant
      women may be warranted.

PMID- 16087985
TI  - Zinc supplementation and psychosocial stimulation: effects on the development of
      undernourished Jamaican children.
AB  - BACKGROUND: Undernourished children have poor levels of development that benefit
      from stimulation. Zinc deficiency is prevalent in undernourished children and may
      contribute to their poor development. OBJECTIVE: We assessed the effects of zinc
      supplementation and psychosocial stimulation given together or separately on the
      psychomotor development of undernourished children. DESIGN: This was a randomized
      controlled trial with 4 groups: stimulation alone, zinc supplementation alone,
      both interventions, and control (routine care only). Subjects were 114 children
      aged 9-30 mo and below -1.5 z scores of the National Center for Health Statistics
      weight-for-age references who were recruited from 18 health clinics. Clinics were
      randomly assigned to receive stimulation or not; individual children were
      randomly assigned to receive zinc or placebo. The stimulation program comprised
      weekly home visits during which play was demonstrated and maternal-child
      interactions were encouraged. The supplementation was 10 mg Zn as sulfate daily
      or placebo. Development (assessed by use of the Griffiths Mental Development
      Scales), length, and weight were measured at baseline and 6 mo later. Weekly
      morbidity histories were taken. RESULTS: Significant interactions were found
      between zinc supplementation and stimulation. Zinc benefited the developmental
      quotient only in children who received stimulation, and benefits from zinc to
      hand and eye coordination were greater in stimulated children. Zinc
      supplementation alone improved hand and eye coordination, and stimulation alone
      benefited the developmental quotient, hearing and speech, and performance. Zinc
      supplementation also reduced diarrheal morbidity but did not significantly
      improve growth. CONCLUSION: Zinc supplementation benefits development in
      undernourished children, and the benefits are enhanced if stimulation is also
      provided.

PMID- 16087986
TI  - Short-term effects of vitamin A and antimalarial treatment on erythropoiesis in
      severely anemic Zanzibari preschool children.
AB  - BACKGROUND: The pathophysiology of anemia in coastal East Africa is complex.
      Impaired erythropoietin production is one possible mechanism. Plasmodium
      falciparum malaria has been found to blunt erythropoietin production, whereas
      vitamin A stimulates erythropoietin production in vitro. OBJECTIVE: We
      investigated the 72-h effects of vitamin A and the antimalarial drug sulfadoxine
      pyramethamine (SP) on erythropoietin production in severely anemic (hemoglobin <
      or = 70 g/L) preschool children in Zanzibar, a region of known vitamin A
      deficiency. We hypothesized that both treatments would stimulate erythropoietin
      production directly, within 72 h, before a change in hemoglobin would occur.
      DESIGN: One hundred forty-one severely anemic children were identified during the
      baseline assessment of a morbidity substudy of a community-based micronutrient
      supplementation trial. All severely anemic children were randomly assigned to
      receive either vitamin A (100,000 or 200,000 IU depending on age) or SP at
      baseline; 72 h later they received the opposite treatment plus daily hematinic
      syrup for 90 d. Erythropoietic and parasitic indicators were assessed at baseline
      and again after 72 h. RESULTS: After 72 h, SP reduced the malaria parasite
      density (by 5029 parasites/microL; P < 0.001), CRP concentrations (by 10.6 mg/L;
      P = 0.001), and the proportion of children infected with malaria (by 32.4%; P <
      0.001). Vitamin A reduced CRP (by 9.6 mg/L; P = 0.011), serum ferritin (by 18.1
      microg/L; P = 0.042), and erythropoietin (by 194.7 mIU/mL; P = 0.011)
      concentrations and increased the reticulocyte production index (by 0.40; P =
      0.041). CONCLUSIONS: Contrary to our hypothesis, vitamin A significantly
      decreased erythropoietin concentration. The most important effect of both vitamin
      A and SP was the rapid reduction of inflammation. Vitamin A also mobilized iron
      from stores and stimulated the production of new erythrocytes.

PMID- 16087987
TI  - Body-composition alterations consistent with cachexia in children and young
      adults with Crohn disease.
AB  - BACKGROUND: Crohn disease (CD) in children is associated with low body mass index
      (BMI), poor growth, and delayed maturation; alterations in lean and fat mass,
      however, are poorly characterized. OBJECTIVE: The objective was to quantify lean
      and fat mass in children and young adults with CD and in healthy control
      subjects, relative to height and pubertal maturation. DESIGN: This cross
      sectional study assessed whole-body lean and fat mass by using dual-energy X-ray
      absorptiometry in 104 subjects with CD and in 233 healthy control subjects aged 4
      25 y. Linear regression was used to determine the effect of CD on body
      composition and to generate sex-specific SD scores (z scores) for lean and fat
      mass relative to height. RESULTS: Subjects with CD had lower height-for-age and
      BMI-for-age z scores (P < 0.001 for both) than did control subjects. CD was
      associated with significant deficits in lean mass after adjustment for height,
      age, race, and Tanner stage (P = 0.003); deficits in fat mass were not observed.
      The mean (+/-SD) lean mass-for-height and fat mass-for-height z scores in the
      subjects with CD were -0.61 +/- 0.92 and -0.04 +/- 0.86, respectively. Within the
      control group, fat mass-for-height was positively correlated with lean mass-for
      height (r = 0.41, P < 0.0001); this association was absent in the subjects with
      CD. CONCLUSIONS: Children and young adults with CD had significant deficits in
      lean mass but preserved fat mass, which is consistent with cachexia. Further
      research is needed to identify physical activity, nutritional, and
      antiinflammatory interventions to improve body composition in persons with CD.

PMID- 16087988
TI  - Effect of sucrose on inflammatory markers in overweight humans.
AB  - BACKGROUND: Observational studies have found that dietary glycemic load is
      positively associated with C-reactive protein (CRP) concentrations in healthy
      humans, which suggests that the type of carbohydrate ingested influences
      inflammatory activity. OBJECTIVE: We investigated the effect of a diet with a
      high content of sucrose or artificial sweeteners on the inflammatory markers CRP,
      haptoglobin, and transferrin in overweight subjects. DESIGN: Overweight men and
      women consumed daily food and drink supplements containing either sucrose [n =
      21; body mass index (BMI, in kg/m2): 28.0] or artificial sweeteners (n = 20; BMI:
      27.6), predominantly from soft drinks (70%; average approximately 1.3 L/d) for 10
      wk. RESULTS: During the intervention, sucrose intake increased by 151% in the
      sucrose group and decreased by 42% in the sweetener group, resulting in a 1.6-kg
      weight gain in the sucrose group and a 1.2-kg weight loss in the sweetener group
      over 10 wk (P < 0.001). Concentrations of haptoglobin, transferrin, and CRP
      increased by 13%, 5%, and 6%, respectively, in the sucrose group and decreased by
      16%, 2%, and 26%, respectively, in the sweetener group (between-group
      differences: P = 0.006, P = 0.01, and P = 0.1, respectively). Adjustment for
      changes in body weight and energy intake did not substantially influence this
      outcome. CONCLUSIONS: The study shows that in the present group of overweight
      subjects a high consumption of sugar-sweetened foods and drinks increased
      haptoglobin and transferrin but had, at best, only a limited influence on CRP.

PMID- 16087989
TI  - Sarcopenia, obesity, and inflammation--results from the Trial of Angiotensin
      Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors study.
AB  - BACKGROUND: Age-related body-composition changes are associated with health
      related outcomes in elders. This relation may be explained by inflammation and
      hemostatic abnormalities. OBJECTIVES: Our objectives were to evaluate the
      relation between body-composition measures [body mass index (BMI), total fat
      mass, and appendicular lean mass (aLM)] and C-reactive protein (CRP), interleukin
      6 (IL-6), and plasminogen activator inhibitor 1 (PAI-1) and to explore the effect
      of obesity and sarcopenia on CRP, IL-6, and PAI-1 concentrations. DESIGN: The
      data are from the Trial of Angiotensin Converting Enzyme Inhibition and Novel
      Cardiovascular Risk Factors (TRAIN) study baseline visit (n = 286; mean age =
      66.0 y). Total fat mass and aLM were assessed with a dual-energy X-ray
      absorptiometry scan. Linear regressions were performed between body-composition
      measures and CRP, IL-6, or PAI-1 concentrations. The effect of sarcopenia and
      obesity (defined as the percentage of fat mass) on CRP, IL-6, and PAI-1
      concentrations was evaluated with the use of analyses of covariance. RESULTS: CRP
      and IL-6 were positively associated with both BMI [beta = 0.027 (P = 0.03) and
      beta = 0.048 (P < 0.001), respectively] and total fat mass [beta = 0.049 (P <
      0.001) and beta = 0.055 (P < 0.001), respectively] and were inversely associated
      with fat-adjusted aLM [beta = -0.629 (P = 0.002) and beta = -0.467 (P = 0.02),
      respectively]. PAI-1 was positively associated with both BMI (beta = 0.038, P =
      0.005) and total fat mass (beta = 0.032, P = 0.007). No significant interaction
      was found between either obesity or sarcopenia and CRP, IL-6, and PAI-1
      concentrations. Obesity remained significantly associated with high CRP and IL-6
      concentrations after adjustments for sarcopenia. CONCLUSIONS: CRP and IL-6 are
      positively associated with total fat mass and negatively associated with aLM.
      Obesity-associated inflammation may play an important role in the age-related
      process that leads to sarcopenia. The relation of inflammation with sarcopenia
      was not independent of any of the considered obesity indexes.

PMID- 16087990
TI  - Different modes of weight loss in Alzheimer disease: a prospective study of 395
      patients.
AB  - BACKGROUND: Alzheimer disease is often accompanied and worsened by malnutrition.
      Patterns of weight loss can differ by the patients concerned and by the outcome
      and interventions required. OBJECTIVE: Our aim was to describe and analyze 2
      modes of weight loss (progressive and severe) in the course of Alzheimer disease.
      DESIGN: This was a prospective study of 395 patients with Alzheimer disease, who
      had a mean age of 75.4 y. A standardized gerontologic evaluation was conducted at
      6 mo and 1 y, including assessments of nutrition, neuropsychology, function, and
      caregiver burden. RESULTS: We investigated 2 modes of weight loss. The first,
      progressive loss (4% in 1 y), affected 33.4% of subjects. Disease severity was a
      risk factor [odds ratio (OR): 7.2; 95% CI: 1.4, 38.2 for a Reisberg score > or =
      5], whereas treatment with cholinesterase inhibitors at baseline decreased this
      risk (OR: 0.33; 95% CI: 0.14, 0.79). The second mode of weight loss, a severe
      loss of > or =5 kg in 6 mo, affected 10.2% of subjects. The existence of an acute
      phase reaction was a risk factor (OR: 2.4; 95% CI: 1.2, 4.8), as was an
      intercurrent event, such as hospitalization, acute disease, institutionalization,
      and change of living arrangements (OR: 6.8; 95% CI: 1.2, 39.9). CONCLUSION:
      During the follow-up of patients with Alzheimer disease, risk factors for these 2
      modes of weight loss should be sought to identify patients who would benefit from
      a nutritional intervention. Our findings lead us to advocate follow-up, which
      involves an assessment of functional, nutritional, and neuropsychologic status
      every 6 mo.

PMID- 16087991
TI  - Biochemical indicators of B vitamin status in the US population after folic acid
      fortification: results from the National Health and Nutrition Examination Survey
      1999-2000.
AB  - BACKGROUND: Mandatory folic acid fortification of cereal-grain products was
      introduced in the United States in 1998 to decrease the risk that women will have
      children with neural tube defects. OBJECTIVE: The objective was to determine the
      effect of folic acid fortification on concentrations of serum and red blood cell
      (RBC) folate, serum vitamin B-12, and plasma total homocysteine (tHcy) and
      methylmalonic acid (MMA) in the US population. DESIGN: Blood was collected from a
      nationally representative sample of approximately 7300 participants aged > or = 3
      y in the National Health and Nutrition Examination Survey (NHANES) during 1999
      2000 and was analyzed for these B vitamin-status indicators. The results were
      compared with findings from the prefortification survey NHANES III (1988-1994).
      RESULTS: The reference ranges (5th-95th percentiles) were 13.1-74.3 nmol/L for
      serum folate, 347-1167 nmol/L for RBC folate, and 179-738 pmol/L for serum
      vitamin B-12. For plasma tHcy and MMA, the reference ranges for serum vitamin B
      12-replete participants with normal serum creatinine concentrations were 3.2-10.7
      mumol/L and 60-210 nmol/L, respectively. The prevalence of low serum folate
      concentrations (<6.8 nmol/L) decreased from 16% before to 0.5% after
      fortification. In elderly persons, the prevalence of high serum folate
      concentrations (>45.3 nmol/L) increased from 7% before to 38% after
      fortification; 3% had marginally low serum vitamin B-12 concentrations (<148
      pmol/L) and 7% had elevated plasma MMA concentrations (>370 nmol/L). Seventy
      eight percent of the US population had plasma tHcy concentrations <9 micromol/L.
      CONCLUSIONS: Every segment of the US population appears to benefit from folic
      acid fortification. Continued monitoring of B vitamin concentrations in the US
      population is warranted.

PMID- 16087992
TI  - Dietary beta-cryptoxanthin and inflammatory polyarthritis: results from a
      population-based prospective study.
AB  - BACKGROUND: Epidemiologic studies suggest that the antioxidant potential of
      dietary carotenoids may protect against the oxidative damage that can result in
      inflammation. OBJECTIVE: We investigated the hypothesis that some dietary
      carotenoids are associated with a reduced risk of developing inflammatory
      polyarthritis (IP). DESIGN: The European Prospective Investigation of Cancer
      Incidence (EPIC)-Norfolk study is a population-based, prospective study of
      >25,000 subjects who completed a baseline 7-d diet diary and were followed up to
      identify new cases of IP, which was defined as synovitis that affected > or = 2
      joint groups. Dietary carotenoid intakes were computed from the diet diaries of
      these subjects, and a nested, case-control analysis was undertaken to compare
      carotenoid intake between case subjects and age- and sex-matched control
      subjects. RESULTS: Eighty-eight incident cases of IP that occurred in the
      population surveyed were ascertained via the Norfolk Arthritis Register. The mean
      daily intakes of zeaxanthin and beta-cryptoxanthin were 20% and 40% lower,
      respectively, in the cases than in the 176 controls, but there were no
      significant differences in the intakes of either lutein or lycopene. Those
      subjects in the top one-third of intake of zeaxanthin and beta-cryptoxanthin were
      at a lower risk of developing IP than were subjects in the lowest one-third [odds
      ratios (95% CI): 0.48 (0.24, 0.94) and 0.51 (0.25, 1.02) for zeaxanthin and beta
      cryptoxanthin, respectively]. The association with beta-cryptoxanthin was
      significant after adjustments were made for total energy and protein intakes and
      for cigarette smoking. CONCLUSION: These data are consistent with previous
      evidence showing that a modest increase in beta-cryptoxanthin intake, equivalent
      to one glass of freshly squeezed orange juice per day, is associated with a
      reduced risk of developing inflammatory disorders such as rheumatoid arthritis.

PMID- 16087993
TI  - Anthropometric indicators of body composition in young adults: relation to size
      at birth and serial measurements of body mass index in childhood in the New Delhi
      birth cohort.
AB  - BACKGROUND: South Asians have a muscle-thin but adipose body phenotype and high
      rates of obesity-related disease. Adult body composition may be predictable in
      early life. OBJECTIVE: Anthropometric indexes of adult body composition were
      examined in relation to birth size and body mass index (BMI) during childhood.
      DESIGN: A population-based cohort of 1526 men and women aged 26-32 y in Delhi,
      India, who were measured sequentially from birth until 21 y of age were followed
      up. Adult weight, height, skinfold thicknesses, and waist and hip circumferences
      were measured. BMI and indexes of adiposity (sum of skinfold thicknesses),
      central adiposity (waist-hip ratio), and lean mass (residual values after
      adjustment of BMI for skinfold thicknesses and height) were derived. RESULTS:
      Mean birth weight was 2851 g. As children, many subjects were underweight-for-age
      (>2 SDs below the National Center for Health Statistics mean; 53% at 2 y), but as
      adults, 47% were overweight, 11% were obese, and 51% were centrally obese
      (according to World Health Organization criteria). Birth weight was positively
      related to adult lean mass (P < 0.001) and, in women only, to adiposity (P =
      0.006) but was unrelated to central adiposity. BMI from birth to age 21 y was
      increasingly strongly positively correlated with all outcomes. BMI and BMI gain
      in infancy and early childhood were correlated more strongly with adult lean mass
      than with adiposity or central adiposity. Higher BMI and greater BMI gain in late
      childhood and adolescence were associated with increased adult adiposity and
      central adiposity. CONCLUSIONS: Birth weight and BMI gain during infancy and
      early childhood predict adult lean mass more strongly than adult adiposity.
      Greater BMI gain in late childhood and adolescence predicts increased adult
      adiposity.

PMID- 16087994
TI  - Polymorphism of the 5-HT2A receptor gene and food intakes in children and
      adolescents: the Stanislas Family Study.
AB  - BACKGROUND: Serotonin (5-hydroxytryptamine; 5-HT) is a key mediator in the
      control of food intake and is probably involved in the etiology of anorexia
      nervosa. An association between a polymorphism of the 5-HT receptor (5-HT2A) gene
      promoter (-1438G/A) and anorexia nervosa has been reported. OBJECTIVE: We
      investigated the relation between the -1438G/A polymorphism of the 5-HT(2A) gene
      and the energy and macronutrient intakes of children and adolescents. DESIGN:
      This cross-sectional study included 370 children and adolescents aged 10-20 y
      (176 boys and 194 girls from 251 families) drawn from the Stanislas Family Study.
      Energy and macronutrient intakes were assessed by using 3-d food records. The 
      1438G/A polymorphism was analyzed by polymerase chain reaction and then by Hpa II
      digestion. RESULTS: In the overall group, after adjustment for age, sex, weight,
      height, and family correlation, the A allele was significantly associated with
      lower energy (P for trend = 0.045) and with total, monounsaturated, and saturated
      fat intakes expressed in g/d (P for trend = 0.007, 0.005, and 0.006,
      respectively). Subjects with the GA genotype had intermediate values. In
      addition, genotype x sex and genotype x age interactions were not significant.
      CONCLUSIONS: The 5-HT2A gene polymorphism in the promoter region is associated
      with energy and fat intakes in young people. This could be explained by the role
      of the serotonergic system as a determinant of food intakes and eating behavior.

PMID- 16087995
TI  - A combination of prebiotic short- and long-chain inulin-type fructans enhances
      calcium absorption and bone mineralization in young adolescents.
AB  - BACKGROUND: Short-term studies in adolescents have generally shown an enhancement
      of calcium absorption by inulin-type fructans (prebiotics). Results have been
      inconsistent; however, and no studies have been conducted to determine whether
      this effect persists with long-term use. OBJECTIVE: The objective was to assess
      the effects on calcium absorption and bone mineral accretion after 8 wk and 1 y
      of supplementation with an inulin-type fructan. DESIGN: Pubertal adolescents were
      randomly assigned to receive 8 g/d of a mixed short and long degree of
      polymerization inulin-type fructan product (fructan group) or maltodextrin
      placebo (control group). Bone mineral content and bone mineral density were
      measured before randomization and after 1 y. Calcium absorption was measured with
      the use of stable isotopes at baseline and 8 wk and 1 y after supplementation.
      Polymorphisms of the Fok1 vitamin D receptor gene were determined. RESULTS:
      Calcium absorption was significantly greater in the fructan group than in the
      control group at 8 wk (difference: 8.5 +/- 1.6%; P < 0.001) and at 1 y
      (difference: 5.9 +/- 2.8%; P = 0.04). An interaction with Fok1 genotype was
      present such that subjects with an ff genotype had the least initial response to
      fructan. After 1 y, the fructan group had a greater increment in both whole-body
      bone mineral content (difference: 35 +/- 16 g; P = 0.03) and whole-body bone
      mineral density (difference: 0.015 +/- 0.004 g/cm(2); P = 0.01) than did the
      control group. CONCLUSION: Daily consumption of a combination of prebiotic short-
      and long-chain inulin-type fructans significantly increases calcium absorption
      and enhances bone mineralization during pubertal growth. Effects of dietary
      factors on calcium absorption may be modulated by genetic factors, including
      specific vitamin D receptor gene polymorphisms.

PMID- 16087996
TI  - Vitamin D and bone mineral density status of healthy schoolchildren in northern
      India.
AB  - BACKGROUND: Current data on the prevalence of vitamin D deficiency in India are
      scarce. OBJECTIVE: We assessed the calcium-vitamin D-parathyroid hormone axis in
      apparently healthy children from 2 different socioeconomic backgrounds in New
      Delhi, India. DESIGN: Clinical evaluation for evidence of vitamin D deficiency
      was carried out in 5137 apparently healthy schoolchildren, aged 10-18 y,
      attending lower (LSES) and upper (USES) socioeconomic status schools. Serum
      calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D
      [25(OH)D], and immunoreactive parathyroid hormone were measured in 760 children
      randomly selected from the larger cohort. Bone mineral density of the forearm and
      the calcaneum was measured in 555 children by using peripheral dual-energy X-ray
      absorptiometry. RESULTS: Clinical evidence of vitamin D deficiency was noted in
      10.8% of the children. Children in the LSES group had a significantly (P < 0.01)
      lower 25(OH)D concentration (10.4 +/- 0.4 ng/mL) than did those in the USES group
      (13.7 +/- 0.4 ng/mL). Concentrations of 25(OH)D <9 ng/mL were seen in 35.7% of
      the children (42.3% in LSES; 27% in USES; P < 0.01). Boys had significantly (P =
      0.004) higher 25(OH)D concentrations than did girls. There was a significant
      negative correlation between the mean serum immunoreactive parathyroid hormone
      and 25(OH) D concentrations (r = -0.202, P < 0.001). Mean forearm bone mineral
      density was significantly (P < 0.01) higher in the USES group than in the LSES
      group. CONCLUSION: A high prevalence of clinical and biochemical hypovitaminosis
      D exists in apparently healthy schoolchildren in northern India.

PMID- 16087997
TI  - Origins and evolution of the Western diet: implications of iodine and seafood
      intakes for the human brain.

PMID- 16087998
TI  - Breastfeeding and risk of inflammatory bowel disease: results of a pediatric,
      population-based, case-control study.

PMID- 16087999
TI  - Effects of theobromine should be considered in future studies.

PMID- 16088000
TI  - Breastfeeding and risk of inflammatory bowel disease.

PMID- 16088001
TI  - Safety of vitamin C.

PMID- 16088002
TI  - Stable isotope labeling of Arabidopsis thaliana cells and quantitative proteomics
      by mass spectrometry.
AB  - Quantitative analysis of protein expression is an important tool for the
      examination of complex biological systems. Albeit its importance, quantitative
      proteomics is still a challenging task because of the high dynamic range of
      protein amounts in the cell and the variation in the physical properties of
      proteins. Stable isotope labeling by amino acids in cell culture (SILAC) has been
      successfully used in yeast and mammalian cells to measure relative protein
      abundance by mass spectrometry. Here we show for the first time that proteins
      from Arabidopsis thaliana cell cultures can be selectively isotope-labeled in
      vivo by growing cells in the presence of a single stable isotope-labeled amino
      acid. Among the tested amino acids ([2H3]-leucine, [13C6]arginine, and
      [2H4]lysine), [13C6]arginine proved to be the most suitable. Incorporation of
      [13C6]arginine into the proteome was homogeneous and reached efficiencies of
      about 80%. [13C6]Arginine-labeled A. thaliana suspension cells were used to study
      the regulation of glutathione S-transferase expression in response to abiotic
      stress caused by salicylic acid and to identify proteins that bind specifically
      to phosphorylated 14-3-3 binding motifs on synthesized bait peptides in affinity
      purification experiments. In conclusion, the combination of stable isotope
      labeling of plant cells and mass spectrometry is a powerful technology that can
      be applied to study complex biological processes that involve changes in protein
      expression such as cellular responses to various kinds of stress or activation of
      cell signaling.

PMID- 16088003
TI  - An empowering medical model of mental health care.

PMID- 16088004
TI  - Antipsychotic prescribing trends among youths, 1997-2002.

PMID- 16088005
TI  - Personal accounts: from the depths of despair to a mission of advocacy.

PMID- 16088006
TI  - Pharmacy costs: finding a role for quality.

PMID- 16088007
TI  - Review of treatment recommendations for persons with a co-occurring affective or
      anxiety and substance use disorder.
AB  - OBJECTIVE: The authors review and evaluate the literature and guidelines on care
      for individuals with a co-occurring affective or anxiety disorder and substance
      use disorder. METHODS: MEDLINE and PsycINFO computerized searches of the English
      language literature were conducted for the period 1990-2002. These articles were
      supplemented with searches of the Cochrane Database of Systematic Reviews (1990
      to 2002) and with articles that were sent to the authors by experts in the field
      to review. Bibliographies of selected papers were hand searched for additional
      articles. From these searches a total of 219 articles were found, of which 127
      were selected for review. RESULTS AND DISCUSSION: The literature shows that, over
      the past several decades, treatment for co-occurring disorders has undergone a
      broad shift in approach, from treating substance abuse before providing mental
      health care to providing simultaneous treatment for each disorder, regardless of
      the status of the comorbid condition. Many treatment recommendations are
      supported by a broad consensus. However, despite this broad agreement,
      recommendations are often not specific enough to guide clinical care. Most
      recommendations with specificity are for acute pharmacotherapy, but even specific
      recommendations lag behind current clinical practice. Although the use of
      psychotropic medication for mental illness is encouraged, experts disagree as to
      whether it is necessary to wait for abstinence before beginning pharmacotherapy.
      In addition, most diagnosis-specific guidelines are silent as to whether the
      specific treatment recommendation applies to co-occurring disorders. Finally,
      empirical evidence is lacking for most recommendations. The authors conclude that
      the mental health and substance abuse treatment fields need to consider its
      research priorities and how to address the multitude of potential combinations of
      disorders.

PMID- 16088008
TI  - Association between concurrent depression and anxiety and six-month outcome of
      addiction treatment.
AB  - OBJECTIVES: This six-month prospective study of 326 patients with substance use
      disorders assessed rates of depression and anxiety symptoms among patients
      entering addiction treatment and examined the effects of concurrent psychiatric
      symptoms on indicators of addiction treatment outcome. METHODS: Initial
      assessments included semistructured clinical interviews, the Addiction Severity
      Index (ASI), the Beck Depression Inventory (BDI), and the Symptom Checklist 90
      Revised (SCL90-R). Patients were reassessed at six months to determine treatment
      outcome (abstinence status and duration of continuous abstinence). RESULTS: A
      majority of the sample (63 percent) had significant psychiatric symptoms at
      intake: 15 percent (N=49) presented with depressive symptoms, 16 percent (N=53)
      with anxiety symptoms, and 32 percent (N=105) with combined depressive and
      anxiety symptoms. Forty percent of patients who presented with combined
      depression and anxiety symptoms were abstinent at six months. These patients
      fared worse than those who were less symptomatic at intake, including those who
      presented with depression symptoms alone; in the latter group, 73 percent were
      abstinent at six months. The hierarchical regression models accounted for 22
      percent of the variance in the duration of continuous abstinence, 26 percent of
      the variance in the frequency of drug use at six months, and 39 percent of the
      variance in abstinence status at six months. Key predictor variables included
      days in treatment, primary drug of abuse, frequency of drug use, and report of
      concurrent depression or anxiety symptoms at intake. CONCLUSIONS: Concurrent
      depression or anxiety symptoms at intake had a small but significant predictive
      effect on addiction treatment outcome over and above factors that are clearly
      known to influence outcome (length of stay in treatment and initial addiction
      severity).

PMID- 16088009
TI  - Factors that influence staffing of outpatient substance abuse treatment programs.
AB  - OBJECTIVE: This study examined whether and how various organizational and
      environmental forces influence staffing in outpatient substance abuse treatment
      programs. METHODS: The authors used data from the 1995 and 2000 waves of the
      National Drug Abuse Treatment System Survey (NDATSS), a telephone survey of unit
      directors and clinical supervisors. Multivariate analyses with generalized
      estimating equations were conducted. Two measures of staffing were modeled: the
      number of weekly treatment hours per client, and active caseload. RESULTS:
      Managed care activity influenced active caseloads but not the number of treatment
      hours per client. Significant differences were noted in staffing levels among
      private for-profit, private nonprofit, and public treatment programs, with public
      units offering fewer hours per client and having larger caseloads. Units
      accredited by the Joint Commission on Accreditation of Healthcare Organizations
      offered more treatment hours per client. CONCLUSIONS: The results of this study
      contribute to the understanding of various influences on treatment staff time and
      caseloads. Understanding these relationships is critical for policy makers,
      managed care companies, and managers, because staffing levels have the potential
      to affect both the cost and the quality of treatment.

PMID- 16088010
TI  - The costs and outcomes of treatment for opioid dependence associated with
      posttraumatic stress disorder.
AB  - OBJECTIVE: This study examined the costs and outcomes of treatment for opiate
      dependence associated with posttraumatic stress disorder (PTSD). METHODS: Data
      were collected on the use of opiate treatment over a 12-month period for a cohort
      of 495 individuals, of whom 42 percent had PTSD. Total treatment costs were
      calculated as the sum of the time spent in each treatment modality multiplied by
      the appropriate unit cost. Outcome measures included occupational functioning,
      use of heroin and other drugs, and physical and mental health. RESULTS: No
      significant difference was noted in the cost of treatment over the 12-month
      period for persons with and without PTSD (5,394+/-5,136 and 4,821+/-5,144
      [Australian dollars], respectively). However, persons with PTSD had poorer
      treatment outcomes in terms of occupational functioning, overdose, and physical
      and mental health. CONCLUSIONS: Although the same resources were invested in
      opiate treatment for persons with and without PTSD, PTSD continued to be
      associated with poorer functioning in a number of domains at 12-month follow-up.
      A well-designed intervention targeting both heroin dependence and PTSD may help
      to improve the outcomes of persons with PTSD.

PMID- 16088011
TI  - Use of substance abuse services by young uninsured american adults.
AB  - OBJECTIVES: This study examined the prevalence and correlates of substance abuse
      service use among uninsured young adults aged 18 to 34 years (N=24,282). METHODS:
      Data were drawn from the 1999 National Household Survey on Drug Abuse. Logistic
      regression was used to identify correlates of substance abuse service use among
      persons who met DSM-IV criteria for dependence. RESULTS: Among uninsured young
      adults (N=5,067), 66 percent lacked any health care coverage for at least one
      year. In this uninsured group, 72 percent were past-year users of alcohol or
      drugs (N=2,335). Among past-year alcohol users (N=2,273), 12 percent met criteria
      for alcohol dependence; among past-year drug users (N=864), 21 percent met
      dependence criteria. Eighty-seven percent of the uninsured young adults with
      alcohol or drug dependence did not receive any substance abuse treatment services
      in the previous year. In the uninsured substance-dependent group, women, blacks,
      and Hispanics were less likely than men and whites to use substance abuse
      services. Among those with substance dependence, uninsured persons were more
      likely than privately insured persons to receive substance abuse services from
      the self-help or human service (nonmedical) sector. CONCLUSIONS: Racial, ethnic,
      and gender disparities in the use of substance abuse services are notable among
      young adults who lack health insurance.

PMID- 16088012
TI  - Use of mental health care and substance abuse treatment among adults with co
      occurring disorders.
AB  - OBJECTIVES: This study investigated patterns of use of mental health care and
      substance abuse treatment for a nationally representative sample of adults with
      co-occurring mental health problems and a substance use disorder and compared
      these patterns with those of persons with either a mental health problem or a
      substance use disorder. METHODS: Data were from the 2001 and 2002 National
      Surveys on Drug Use and Health. The study examined rates of substance use
      disorders and mental health problems among adults aged 18 years and older, rates
      of substance use disorders among adults with mental health problems, and rates of
      mental health problems among adults with substance use disorders. Next, rates of
      substance abuse treatment and mental health care use were calculated among five
      groups that were formed on the basis of the presence of a substance use disorder,
      mental health problems, or both in the past year. RESULTS: A total of 2,851
      respondents had a substance use disorder only, 1,633 had a substance use disorder
      with one or more mental health symptoms and without serious mental illness, 1,872
      had a substance use disorder with serious mental illness, 13,759 had one or more
      mental health symptoms only, and 7,530 had a serious mental illness only. A
      substantial proportion of adults with comorbid mental health problems and a
      substance use disorder did not receive any treatment (46 percent of those with
      serious mental illness and 65 percent of those with one or more mental health
      symptoms). Co-occurring substance use disorder was not associated with increased
      use of mental health care. The likelihood of receiving any substance abuse
      treatment increased with the presence and severity of mental health problems.
      Across all five groups, use of mental health care was more common than use of
      substance abuse treatment. Less than one-third of patients with comorbid mental
      health problems and a substance use disorder who used mental health care also
      received substance abuse treatment. CONCLUSIONS: The large proportion of
      untreated individuals with mental and substance use disorders reinforces existing
      concerns about barriers to beneficial treatment. Low rates of use of substance
      abuse treatment among patients who have comorbid mental health problems and a
      substance use disorder and use mental health care suggest that recommendations
      that substance use disorders be treated before, or concurrently with, mental
      disorders have not been widely adopted.

PMID- 16088013
TI  - Cost-sharing requirements and access to mental health care among medicare
      enrollees with schizophrenia.
AB  - OBJECTIVE: This study explored the association between Medicare cost-sharing
      requirements and the probability of use of various mental health outpatient
      services among Medicare enrollees with schizophrenia. METHODS: Multivariate
      logistic regression was used to estimate the probability of use of each of seven
      types of services over six months. Patients were recruited from public and
      private mental health treatment provider organizations in six states. The
      analyses included 1,088 Medicare enrollees, of whom approximately 55 percent were
      also enrolled in Medicaid. RESULTS: Medicare-only patients (with greater cost
      sharing) were 25 to 45 percent less likely to have used rehabilitation services,
      individual therapy with nonpsychiatrist mental health providers, and case
      management. No association was found between Medicaid enrollment and probability
      of service use for medical clinic visits, group therapy, individual contact with
      a psychiatrist, or receipt of second-generation antipsychotics. CONCLUSIONS:
      Among Medicare enrollees with schizophrenia, gaps in Medicare coverage may be
      more problematic for rehabilitation, case management, and contact with
      nonpsychiatrist providers. Local public and private subsidies for mental health
      treatment may compensate for some of the gaps in coverage. However, such
      subsidies are not universally or uniformly provided.

PMID- 16088014
TI  - Use of a consumer-led intervention to improve provider competencies.
AB  - OBJECTIVE: Client-centered care is a major aim of health care. In mental health,
      new client-centered treatment approaches that emphasize recovery, rehabilitation,
      and empowerment can improve outcomes for people with severe and persistent mental
      illness. However, these approaches are not widely used, in part because many
      clinicians lack the necessary competencies. The objective of this study was to
      evaluate the effectiveness of an innovative, consumer-led intervention, Staff
      Supporting Skills for Self-Help, which was designed to improve provider quality,
      empower mental health consumers, and promote mutual support. METHODS: The study
      was conducted at five large community mental health provider organizations in two
      western states. One organization in each state received the intervention. The
      intervention included education, clinician-client dialogues, ongoing technical
      assistance, and support of self-help. It focused on client-centered care,
      rehabilitation, and recovery. A one-year controlled trial evaluated the effect of
      the intervention on clinicians' competencies, care processes, and the formation
      of mutual support groups. Outcomes were assessed by using competency assessment
      survey instruments and semistructured interviews with clinicians and managers.
      RESULTS: A total of 269 clinicians participated in the study: 151 in the
      intervention group and 118 in the control group. Compared with clinicians at the
      control organizations, clinicians at intervention organizations showed
      significantly greater improvement in education about care, rehabilitation
      methods, natural supports, holistic approaches, teamwork, overall competency, and
      recovery orientation. CONCLUSIONS: A feasible, consumer-led intervention improves
      provider competencies in domains that are necessary for the provision of high
      quality care.

PMID- 16088015
TI  - A developmental model for rural telepsychiatry.
AB  - Telepsychiatry represents a promising means to increase access to care for rural
      American Indian communities. This article describes rural telepsychiatry clinics
      operated by the American Indian and Alaska Native Programs at the University of
      Colorado Health Sciences Center through a partnership with the Department of
      Veterans Affairs, the Indian Health Service, and local tribal health services
      that target American Indian veterans with posttraumatic stress disorder. A six
      stage model for developing such services is presented. The model consists of
      needs identification, infrastructure survey, partnership organization, structure
      configuration, pilot implementation, and solidification. This article traces
      program development, presents challenges in implementing these services, and
      offers potential solutions. The model can guide the development of telepsychiatry
      services for American Indians specifically and rural populations in general.

PMID- 16088016
TI  - Relationship between entry into child welfare and mental health service use.
AB  - OBJECTIVE: This study examined the relationship between initiation of outpatient
      mental health service use and level of child welfare involvement. METHODS: Three
      levels of child welfare involvement were examined: in-home care and no child
      welfare services beyond an initial investigation, in-home care and additional
      child welfare services, and placement in out-of-home care (foster care).
      Longitudinal data were collected for a subsample of children (N=3,592) aged two
      through 14 years who were enrolled in the National Survey of Child and Adolescent
      Well-Being, a nationally representative sample of children undergoing
      investigation for abuse or neglect. Event history analysis was used to model
      relative risk of initiation of mental health service use over time. RESULTS:
      Hazard functions revealed a large increase in onset of mental health services
      immediately after the time of the initial contact with child welfare, varying by
      level of child welfare involvement and leveling off by three months after the
      initial contact. The multivariate Cox proportional-hazards model indicated that
      compared with children who were placed in out-of-home care, those in in-home care
      who did not receive any further child welfare services were about one-third as
      likely to use mental health services and those in in-home care who received
      additional child welfare services were one-half as likely to use mental health
      services. Other covariates in the model predicted mental health service use,
      including being older, being Caucasian, having a history of maltreatment
      (specifically, physical abuse, physical neglect, or abandonment), being
      uninsured, and need for mental health services, as measured by the Child Behavior
      Checklist. CONCLUSIONS: Contact with child welfare functions as a gateway into
      mental health services for children in child welfare, even when need for such
      services is controlled for.

PMID- 16088017
TI  - Perceived unmet need for mental health treatment and barriers to care among
      patients with panic disorder.
AB  - OBJECTIVE: This study estimated the extent of perceived unmet need for mental
      health treatment among individuals with panic disorder in primary care settings,
      investigated the determinants of unmet need, and assessed barriers to care.
      METHODS: Data were from baseline interviews in a clinical trial that investigated
      primary care treatment of panic disorder. Participants were asked whether there
      was any time in the past three months when they did not get as much care for
      emotional or personal problems as they needed or whether they had delays in
      getting care. Patients who endorsed unmet need were asked about specific
      perceived barriers. Logistic regression was used to investigate the determinants
      of unmet need. RESULTS: Of the 231 patients eligible for the study, 88 (38
      percent) endorsed unmet need for emotional or mental health problems. Individuals
      with worse mental health, those who were more worried about panic, and those
      without sick pay were significantly more likely to report unmet need. Commonly
      reported barriers included being unable to find out where to go for help (43
      percent), worry about cost (40 percent), lack of coverage by health plan (35
      percent), and being unable to get an appointment soon enough (35 percent).
      CONCLUSIONS: The relatively low level of patient-reported unmet need for mental
      health treatment among primary care patients with panic disorder suggests that
      efforts to improve treatment of panic disorder should include patient education
      about mental illness and the effective treatments available. Although discussion
      of barriers to care has traditionally centered on stigma and economic factors,
      the results of this study suggest that simple logistic factors, such as not
      knowing whom to call for help, are also important barriers.

PMID- 16088018
TI  - Characteristics of insured and noninsured outpatients with depression in
      STAR(*)D.
AB  - OBJECTIVE: This study examined data from the first 1,500 patients with major
      depressive disorder who were entered into the Sequenced Treatment Alternatives to
      Relieve Depression (STAR*D) and compared baseline characteristics of outpatients
      on the basis of their insurance status. METHODS: We compared the demographic and
      clinical characteristics and the features of the presenting symptoms of
      outpatients with private insurance, public insurance, Medicaid and Medicare, or
      no insurance who were seeking treatment for depression. RESULTS: Valid insurance
      data were available for 1,452 patients. Compared with patients with private
      insurance, patients with public or no insurance were more likely to be members of
      a racial or ethnic minority group, unmarried, less educated, and unemployed.
      Patients were more likely to attend primary care clinics if they had public
      insurance (46 percent) compared with private insurance (34 percent) or no
      insurance (30 percent). Compared with the other groups, patients with public
      insurance had the greatest number and severity of comorbid medical conditions. In
      general, compared with patients with private insurance, those with public or no
      insurance had greater severity of depression, more comorbid psychiatric symptoms,
      lower life satisfaction scores, and greater functional impairment. These findings
      remained after the analyses adjusted for gender, employment, comorbid medical
      conditions, race, and duration of illness. CONCLUSIONS: Compared with patients
      with private insurance, those with public or no insurance had a more chronic,
      more severe, and more disabling form of depression.

PMID- 16088019
TI  - Pharmacologic management of difficult-to-treat depression in clinical practice.
AB  - OBJECTIVE: This article reviews the concept of difficult-to-treat depression and
      outlines some principles of pharmacologic management. METHODS: The authors
      conducted a MEDLINE review for the years 1999 to 2004, using the key words
      refractory, resistant, and difficult-to-treat depression. RESULTS: Only a small
      body of evidence-based literature exists to guide the management of difficult-to
      treat depression. Nevertheless, clinicians often need to make treatment decisions
      in the absence of clear data. Depression should not be considered resistant,
      refractory, or difficult to treat in the absence of trials in which an
      appropriate drug is given in a dosage and duration sufficient to produce a
      response. Nevertheless, inadequate antidepressant trials are a relatively common
      phenomenon. Nonresponse may also result from pharmacokinetic or pharmacogenomic
      factors. Principals for assessing difficult-to-treat depression include
      preventing pseudo-resistant cases, recognizing that finding the best treatment
      option is a process, developing a systematic step-by-step approach, and
      preserving hope. A review of the literature demonstrated a two-step approach for
      managing difficult-to-treat depression. The first step is to evaluate for factors
      that contribute to nonresponse, such as comorbid medical and psychiatric
      conditions. The second step involves using the four classical strategies for
      enhancing antidepressant efficacy: optimization, augmentation, combination, and
      switching. CONCLUSION: Advances have been made in the treatment of depression,
      but a great deal more research needs to be done. It is hoped that new
      alternatives and promising developments in methods will contribute to the
      improved management of what we now call difficult-to-treat depression.

PMID- 16088020
TI  - Patient Safety Forum: do state Medicaid preferred drug lists affect patient
      safety?

PMID- 16088021
TI  - Assessment and management of patients who make threats against the president in
      the psychiatric emergency service.

PMID- 16088022
TI  - Physicians should not be agents of the police.

PMID- 16088024
TI  - Overstating the case about recovery?

PMID- 16088025
TI  - Further considerations about SQL clinic.

PMID- 16088026
TI  - Ethical issues in surreptitious prescribing.

PMID- 16088027
TI  - Little use of treatment among problem gamblers.

PMID- 16088029
TI  - Trite but true, better safe than sorry.

PMID- 16088032
TI  - Epithelial localization of green fluorescent protein-positive cells in epididymis
      of the GAD67-GFP knock-in mouse.
AB  - gamma-Aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in
      the brain, is also found in many peripheral nonneuronal tissues, including male
      reproductive organs. However, the distribution of GABAergic cells in various
      organs is not known. The GAD67-GFP knock-in mouse is a useful model for studying
      the distribution and morphology of GABAergic neurons in the brain. We examined
      the male reproductive organs of GAD67-GFP knock-in mice by fluorescence
      microscopy and found cells with strong green fluorescent protein (GFP) signal
      exclusively in the epithelium of the initial segment and proximal caput of the
      epididymis. The characteristic cell morphology suggested that these were narrow
      cells. These GFP-positive narrow cells also expressed GAD67 and GABA. Reverse
      transcription polymerase chain reaction (RT-PCR) analysis showed that the
      predominant glutamic acid decarboxylase (GAD) isoform expressed in the epididymis
      is GAD67. RT-PCR analysis also revealed that mRNAs encoding the GABA(A) and
      GABA(B) receptor subunits necessary for the assembly of functional receptors are
      expressed in the epididymis. GABA(A) receptor subunit mRNAs detected in the
      proximal epididymis included alpha2, beta1, gamma1, and gamma3, and both the R1
      and R2 subunit mRNAs of GABA(B) receptors were detected. Immunohistochemical
      analysis of GABA(A) receptor subunit proteins revealed that alpha2, beta1, and
      gamma subunits expressed in spermatozoa, whereas we did not detect these GABA(A)
      receptor subunits in epithelial cells. GABA(B) receptors were produced by narrow
      cells and spermatozoa of GAD67-GFP knock-in and wild-type Jcl:ICR mice. Our data
      suggest that the GABA system might have important functional roles in narrow
      cells and on spermatozoa in the lumen.

PMID- 16088033
TI  - Protein C inhibitor expression by adult rat Sertoli cells: effects of
      testosterone withdrawal and replacement.
AB  - Protein C inhibitor (PCI), a member of the plasma serine protease inhibitor
      family, has been reported to be abundantly expressed in the seminal vesicles and
      testes. In this study, we examine the localization and regulation of the PCI gene
      and protein expression in testes and freshly isolated Sertoli cells from control
      rats, rats treated with luteinizing hormone-suppressive testosterone/estradiol
      (TE)-containing Silastic capsules for 7, 14, 28, and 56 days, and rats treated
      with TE for 56 days, followed by high levels of testosterone for 7 or 14 days.
      The administration of the TE capsules for 56 days resulted in reduced testicular
      testosterone, from approximately 100 ng/mL in the controls to approximately 10
      ng/mL, accompanied by a 73% reduction in testicular weight. PCI mRNA levels in
      freshly isolated Sertoli cells were reduced by 30% and 54% following TE treatment
      for 28 and 56 days, respectively. When rats that had received TE capsules for 56
      days were provided replacement testosterone, there was a 40% increase in PCI mRNA
      levels within 7 days in the absence of any change in testicular weight, and PCI
      mRNA levels returned to control values by 14 days. The decrease in PCI mRNA
      levels in TE-treated rats was paralleled by a decrease in PCI protein levels in
      whole testis lysates and in seminiferous tubule fluid (STF). Protease activity
      was significantly increased in STF following 56 days of TE treatment. Taken
      together, these results indicate that 1) PCI in the testis is expressed by
      Sertoli cells; 2) the testicular expression of PCI is responsive to
      intratesticular testosterone levels; and 3) protease activity within the
      seminiferous epithelium is elevated when intratesticular concentration is
      decreased, perhaps as a consequence of decreased PCI.

PMID- 16088034
TI  - Changes in testosterone and dihydrotestosterone levels in male rat accessory sex
      organs, serum, and seminal fluid after castration: establishment of a new highly
      sensitive simultaneous androgen measurement method.
AB  - It is known that abnormal androgen dynamics in the tissues is a cause of androgen
      dependent disorders. Investigation of tissue androgen levels could provide a clue
      to the elucidation of disorders. However, it is difficult to measure a trace
      amount of androgen in the tissues. We established a highly sensitive simultaneous
      quantification method of testosterone and dihydrotestosterone (DHT), which play
      the most important roles in the body among androgenic steroids in trace amounts,
      and investigated time course changes in testosterone and DHT levels in male
      accessory sex organs, serum, and seminal fluid after castration in rat models. In
      addition, changes in the testosterone/DHT ratio of male accessory sex organs and
      seminal fluid were observed. The simultaneous testosterone and DHT measurement
      method established by us was validated. Intra-assay variation and interassay
      precision and accuracy were all within +/-20%, and the quantification limits of
      testosterone and DHT were both 15.6 pg/g. With the use of this method, the
      testosterone and DHT levels in the prostate, seminal vesicles, and serum
      immediately after castration were similar to those previously reported. The
      testosterone and DHT levels were 350 pg/g and 605 pg/g, respectively; which
      showed dominance of DHT in seminal fluid, although it was not as marked as that
      in the male accessory sex organs. Androgens decreased with time after castration
      in the accessory sex organs, serum, and seminal fluid. In the prostate and
      seminal vesicles, testosterone and DHT decreased to about 50% and about 2% of the
      normal levels, respectively, 72 hours after castration. The serum levels were
      under the quantification limits 6 hours after castration and thereafter. In
      seminal fluid, the testosterone and DHT levels decreased to 49% and 35% of normal
      levels, respectively, 72 hours after castration. The testosterone/DHT ratio in
      the male accessory sex organs was lower in the prostate (0.06) than in the
      seminal vesicles (0.13) immediately after castration. In the seminal fluid,
      changes in the ratio were small compared with those in the accessory sex organs
      and serum. These results showed that our method was capable of measuring
      testosterone and DHT in very small amounts of samples such as prostate biopsy
      specimens, and it might provide a clue to the elucidation of the pathology of
      androgen-dependent disorders.

PMID- 16088035
TI  - Impaired sperm function after spinal cord injury in the rat is associated with
      altered cyclic adenosine monophosphate signaling.
AB  - Our previous observations of changes in the expression of cAMP-dependent genes
      and the cAMP-responsive element modulator (CREM) in rat testicular cells after
      spinal cord injury (SCI) implied abnormal cAMP signaling as one of the mechanisms
      underlying the effects of SCI on spermatogenesis. It was postulated that such
      effects might contribute to abnormal sperm function after SCI. In this study, we
      examined this possibility. In spinal cord-contused (SCC) and -transected (SCX)
      rats, impaired sperm motility was accompanied by an increase in sperm cAMP
      content. Treatment of SCX rats with exogenous testosterone or follicle
      stimulating hormone resulted in a further decrease in sperm motility, whereas
      sperm cAMP either increased or remained unchanged. These effects differed from
      those in sham control rats that received identical treatments. Results of these
      experiments also demonstrated that impaired sperm motility in SCC and SCX rats
      was accompanied by decreases in sperm viability and mitochondrial potential, thus
      suggesting a possible link between these changes. We concluded that impaired
      sperm motility after SCI was associated with decreases in sperm viability and
      mitochondrial potential. These effects occurred in the face of elevated sperm
      cAMP content and changes in its regulation, suggesting that altered cAMP
      signaling events might contribute to impairment of sperm motility and perhaps
      other sperm functions after SCI.

PMID- 16088036
TI  - Prevalence of premature ejaculation in Turkish men with chronic pelvic pain
      syndrome.
AB  - Chronic pelvic pain syndrome is a common and serious health problem affecting the
      quality of life in men. Limited studies exist on the relation of this condition
      to premature ejaculation. We evaluated prevalence rates of premature ejaculation
      in Turkish male patients with chronic pelvic pain syndrome and compared them with
      healthy control subjects. Sixty-six men with chronic pelvic pain syndrome were
      included in the study (group 1). A questionnaire consisting of 2 parts-
      demographic data and a Turkish version of the National Institutes of Health
      Chronic Prostatitis Symptom index--was administered to all patients. Premature
      ejaculation was defined as intravaginal ejaculation latency of less than 2
      minutes with the same partner for at least 6 months. All patients were evaluated
      with physical examinations and routine laboratory tests. If erectile dysfunction
      was noted from the medical history, penile Doppler ultrasonography also was
      performed. The results were compared with the results of 30 healthy men without
      urinary symptoms (group 2). The chi2 test was used for statistical analyses. Of
      66 patients with chronic pelvic pain syndrome, 51 had premature ejaculation
      (77.3%), and in 10 (15.2%) patients, premature ejaculation and erectile
      dysfunction were found together. Penile Doppler ultrasonography showed no
      vascular pathology in patients with erectile dysfunction. The rate of premature
      ejaculation was higher in patients in the study group than it was in patients in
      the control group, and this difference was statistically significant (P < .05).
      Both chronic pelvic pain syndrome and premature ejaculation are common disorders,
      but their ethiopathogeneses are not well understood. In Turkish men with chronic
      pelvic pain syndrome, the incidence of psychogenic sexual problems was higher
      than in the normal population.

PMID- 16088037
TI  - Vardenafil in patients with erectile dysfunction: achieving treatment
      optimization.
AB  - This post hoc analysis of data from a multicenter, randomized, double-blind study
      determined how many attempts were needed to record at least 1 successful
      penetration and maintenance of erection long enough for successful intercourse in
      a broad population of men with erectile dysfunction taking vardenafil at 5, 10,
      or 20 mg or placebo. The cumulative probability of achieving successful
      penetration and of maintaining an erection increased with the number of attempts
      for all 3 vardenafil groups. For the first attempt, the probability of achieving
      successful penetration was higher in all 3 vardenafil groups compared with
      placebo; 67% in the 5-mg vardenafil group, 77% in the 10-mg vardenafil group, and
      74% in the 20-mg vardenafil group compared with 46% for placebo. By the third
      attempt, the probability of at least 1 success was 82% for 5, 88% for 10, and 85%
      for 20 mg vardenafil compared with 68% for placebo. The probability of
      maintaining an erection long enough to complete intercourse at the first attempt
      was 51% for 5, 69% for 10, and 61% for 20 mg vardenafil compared with 28% for the
      placebo group. By the third attempt, the probability of maintaining an erection
      was 66% for 5, 81% for 10, and 77% for 20 mg vardenafil in contrast to 53% for
      placebo. The results of this analysis indicate that patients without initial
      treatment success should continue treatment or increase the dose because the
      cumulative probability of success increases with additional attempts with
      vardenafil, with a plateau at about the fourth dose.

PMID- 16088038
TI  - Kinematic changes during the cryopreservation of boar spermatozoa.
AB  - The present study evaluates the effect that various steps of a conventional cycle
      of cryopreservation have on the patterns of movement exhibited by boar
      spermatozoa. Sperm-rich ejaculate fractions collected from 24 mature fertile
      boars (1 ejaculate per boar) were cryopreserved following a standard freeze-thaw
      procedure with 0.5-mL plastic straws. Overall sperm motility and the individual
      kinematic parameters of motile spermatozoa (assessed by the computer-aided sperm
      analysis system Sperm Class Analyzer [SCA]) were recorded in 5 steps of the
      cryopreservation procedure. These steps were as follows: 1) at the time that the
      fresh semen was extended, 2) at 17 degrees C, after sperm concentration by
      centrifugation and re-extension of the pellet with lactose-egg yolk extender; 3)
      at 5 degrees C, after added freezing extender; 4) at the time that thawed semen
      was held in a water bath at 37 degrees C for 30 minutes; and 5) at the time that
      thawed semen was held in a water bath at 37 degrees C for 150 minutes. Data from
      individual motile spermatozoa, defined by 7 kinematic parameters (curvilinear
      velocity [VCL], straight-line velocity [VSL], average path velocity [VAP],
      linearity [LIN], straightness [STR], mean amplitude of lateral head displacement
      [ALH], and beat cross frequency [BCF]), were analyzed using a pattern analysis
      technique (PATN) to identify and quantify populations and subpopulations of
      motile sperm within the semen samples. After the first cluster analysis, 3 motile
      sperm populations (P) were identified (P1: progressive and/or vigorous cells
      [90.4%], P2: poorly progressive cells [8.3%], and P3: nonprogressive cells
      [1.3%]). These populations remained constant (P > .05) throughout the 5-step
      cryopreservation procedure. A second PATN was carried out within the P1 sperm
      population, which identified 3 sperm subpopulations (sP) (eg, sP1: cells with
      progressive and vigorous movement [58.7%], sP2: progressive cells only [24.6%],
      and sP3: vigorous cells only, hyperactive-like [16.7%]). Although the relative
      frequency of these 3 subpopulations varied among ejaculates (boars), there was no
      interaction with any cryopreservation step we examined. Whereas sP1 remained
      constant (P > .05), sP2 and sP3 varied significantly (P < .05) through the
      cryopreservation procedure, with the increase in sP3 after centrifugation at 17
      degrees C and during cooling at 5 degrees C considered particularly relevant. In
      conclusion, the present study confirms the heterogeneity of sperm movement
      patterns in boar semen, patterns that vary through the cryopreservation
      procedure, especially after removal of the seminal plasma by centrifugation and
      subsequent extension at 17 degrees C and after the slow cooling at 5 degrees C,
      when obvious increases in hyperactivated movement appeared. The vast majority of
      spermatozoa, those exhibiting progressive and vigorous movement, remained
      constant during the cryopreservation procedure, although the proportion differed
      among boars.

PMID- 16088039
TI  - The motility of epididymal or testicular spermatozoa does not directly affect
      IVF/ICSI pregnancy outcomes.
AB  - Our objective was to determine whether the presence of motility in surgically
      obtained sperm samples improves fertilization and pregnancy rates for patients
      undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).
      This was a retrospective study in a hospital-based infertility center. Sixty
      seven couples with a diagnosis of azoospermia or severe oligozoospermia who had
      undergone a sperm retrieval procedure in conjunction with 100 IVF/ICSI cycles
      from 1995 to 2004 were evaluated. The impact of sperm motility on fertilization
      and clinical pregnancy rates was determined. The motile and nonmotile sperm
      groups differed in the number of mature oocytes retrieved (10.7 +/- 5.8 vs 13.4
      +/- 6.0), but fertilization (56.7% vs 59.1%) and embryo cryopreservation rates
      (35.9% vs 39.3%) were statistically similar. Clinical pregnancy rates did not
      differ between the motile (38.5%) and nonmotile (31.2%) groups, nor did they
      differ between obstructive and nonobstructive patients (35.3% vs 26.7%). There
      was also no statistical difference in pregnancy rates between testicular and
      epididymal aspiration (35.3% vs 26.7%), although epididymal sperm were
      significantly more likely to be motile than testicular sperm (100% vs 39.3%, P <
      .0001). Epididymal aspiration is more likely to produce motile sperm than
      testicular sperm retrieval. The use of motile sperm from epididymal or testicular
      samples, however, does not appear to enhance fertilization or clinical pregnancy
      rates.

PMID- 16088040
TI  - Distal ligament in human glans: a comparative study of penile architecture.
AB  - To elucidate the anatomic distal ligament of the human glans penis and associated
      clinical implications, we compared the structures of the glans penis and corpora
      cavernosa in dogs, rats, and humans. From May 2001 to March 2003, gross
      dissection, microscopic examinations, and stains for elastic fibers and collagen
      subtypes were made in the penises of 11 adult human male cadavers, 7 dogs, and 5
      rats. A distal ligament in the human glans penis replaces the os penis that is
      present in dogs or rats, also termed the baculum, but retains collagen types I
      and III as common structural and interlocking components, respectively. The
      intercavernosal septum is complete, and intracavernosal pillars (ICPs) are
      abundant in dogs, absent in rats, and moderately developed in humans. A tunica
      with numerous elastic fibers exists to fulfill the requirements of erectile
      function in humans but not in dogs or rats, since it is essential for
      establishing tissue strength to serve as a buttress. We may conclude that in dogs
      and rats, the strong os penis is designed for ready intromission and is
      associated with a pair of well-developed nonelastic corpora to serve as a
      buttress for the os penis. These structures are necessary for the rigorous coitus
      observed in dogs. The less compliant corpus cavernosum is suitable for the
      flipping action observed in a mating male rat. These specific anatomic designs
      may provide explanations for the individual requirements for the specific
      physiologic functions that differ from species to species. Although there is no
      os in the human glans, a strong equivalent distal ligament is arranged centrally
      and acts as a supporting trunk for the glans penis. Without this important
      structure, the glans could be too weak to bear the buckling pressure generated
      during coitus and too limber to serve as a patent passage for ejaculation, and it
      could be too difficult to transmit the intracavernosal pressure surge along the
      entire penis during ejaculation. Given the common histologic nature of the distal
      ligament, which is associated with the tunica albuginea and serves a similar
      function as the os penis observed in the dog and the rat, one may ask whether the
      healing process of a tunica may take as long as that required in a bony
      structure. Further research is required to answer this question.

PMID- 16088041
TI  - Nonprotein thiols and disulfides in rat epididymal spermatozoa and epididymal
      fluid: role of gamma-glutamyl-transpeptidase in sperm maturation.
AB  - Sperm thiol oxidation during sperm maturation is important for sperm component
      stabilization, the acquisition of sperm motility, and fertilizing ability. A
      correct degree of oxidation is required, since spermatozoa are very susceptible
      to oxidative damage. The pathways involved in physiologic sperm thiol oxidation
      in the epididymis are not completely understood. The nonprotein thiol glutathione
      (GSH), in addition to playing a major role as an antioxidant and in eliminating
      toxic compounds, has been implicated in prooxidation processes in various cells,
      via gamma-glutamyl-transpeptidase (gamma-GT)-dependent catabolism. Little
      information is available on the dynamics of nonprotein thiols (NPSHs) and
      disulfides (NPSSNPs) in spermatozoa and epididymal fluid (EF) during sperm
      passage in the epididymis. It is not clear whether NPSHs and NPSSNPs are involved
      in sperm protein thiol (PSH) oxidation or whether GSH catabolism in the
      epididymis can serve as a pathway for sperm PSH oxidation. In the present study,
      we used the thiol fluorescence labeling agent monobromobimane to analyze NPSHs
      and nonprotein disulfides (NPSSRs) (R, nonprotein or protein) in spermatozoa and
      EF in the rat caput and cauda epididymis. NPSH levels are shown to be
      significantly higher in the caput than in the cauda (spermatozoa and fluid). GSH
      in the caput lumen is subject to high gamma-GT activity. A marked loss of sperm
      GSH and a shift to an oxidized state (resulting in a significantly higher
      concentration of glutathione disulfides [GSSRs] than GSH) occur during the
      passage of spermatozoa from the caput to the cauda epididymis. Caput EF and
      extracellular NPSSNPs induce sperm thiol oxidation. The results suggest that
      epididymal NPSH/NPSSNP participates in sperm PSH oxidation and that some
      reactions of GSH in the gamma-GT pathway (in the epididymis) provide oxidizing
      power, leading to physiologic sperm thiol oxidation.

PMID- 16088043
TI  - The impact of the 2003 heat wave on daily mortality in England and Wales and the
      use of rapid weekly mortality estimates.
AB  - This paper describes a retrospective analysis of the impact of the 2003 heat wave
      on mortality in England and Wales, and compares this with rapid estimates based
      on the Office for National Statistics routine weekly deaths reporting system.
      Daily mortality data for 4 to 13 August 2003, when temperatures were much hotter
      than normally seen in England, were compared with averages for the same period in
      years 1998 to 2002. The August 2003 heat wave was associated with a large short
      term increase in mortality, particularly in London. Ozone and particulate matter
      concentrations were also elevated during the heat wave. Overall, there were 2139
      (16%) excess deaths in England and Wales. Worst affected were people over the age
      of 75 years. The impact was greatest in the London region where deaths in those
      over the age of 75 increased by 59%. Estimated excess mortality was greater than
      for other recent heat waves in the United Kingdom. The estimated number of deaths
      registered each week is reported by the Office for National Statistics. The first
      clear indication of a substantial increase in deaths was published on 21 August
      2003. This provided a quick first estimate of the number of deaths attributable
      to the heat wave and reflected the pattern of daily deaths in relation to the
      hottest days, but underestimated the excess when compared with the later
      analysis.

PMID- 16088044
TI  - The effect of the summer 2003 heat wave on mortality in the Netherlands.
AB  - In the Netherlands, between 1400 and 2200 deaths in the summer of 2003 may have
      been heat-related. The fact that the maximum temperatures were lower than in some
      other European countries, and occurred in less heavily populated areas, may have
      led to mortality figures that were relatively less dramatic. The temporarily
      increased death rates are only partly due to a forward shift of mortality. Heat
      related mortality was most pronounced among the elderly in nursing homes.

PMID- 16088045
TI  - The impact of the summer 2003 heat waves on mortality in four Italian cities.
AB  - This study evaluates the impact of the 2003 heat wave on cause-specific mortality
      and the role of demographic characteristics and socioeconomic conditions that may
      have increased the risk of mortality in four Italian cities: Bologna, Milan, Rome
      and Turin. Daily mortality counts, for the resident population by age, sex and
      cause of death were considered. Daily excess mortality was calculated as the
      difference between the number of deaths observed and the smoothed average. The
      impact of heat on health is measured in terms of maximum apparent temperature.
      The greatest excess in mortality was observed in the north west of Italy (Turin,
      +23% and Milan, +23%). The old (75-84 years) and the very old (85+ years) were
      the age groups most affected, and when stratifying by sex, the increase in
      mortality seemed to be greater among females. The greatest excess in mortality
      was registered in those with low socioeconomic status in Rome (+17.8%) and in
      those with lower education levels in Turin (+43%). The analysis of cause-specific
      mortality not only confirms results from previous studies of an increase in heat
      related mortality by respiratory and cardiovascular diseases, but also shows a
      significant excess in mortality for diseases of the central nervous system and
      for metabolic/endocrine disorders. Results from 2003 highlight the necessity of
      targeting future prevention programmes at the susceptible sub-groups identified.
      The introduction of warning systems alongside efficient preventive plans and the
      monitoring of mortality during heat waves may represent a valid tool for the
      reduction of heat-related deaths.

PMID- 16088046
TI  - Mortality in Spain during the heat waves of summer 2003.
AB  - The effect of the elevated temperatures on mortality experienced in Europe during
      the summer of 2003 was observed in several countries. This study, carried out in
      Spain, describes mortality between 1 June and 31 August and evaluates the effect
      of the heat wave on mortality. Observed deaths were obtained from official death
      registers from 50 provincial capitals. Observed deaths were compared with the
      expected number, estimated by applying a Poisson regression model to historical
      mortality series and adjusting for the upward trend and seasonality observed.
      Meteorological information was provided by the Instituto Nacional de Meteorologia
      (National Institute of Meteorology). Spain experienced three heat waves in 2003.
      The total associated excess deaths were 8% (43 212 observed deaths compared with
      40 046 expected deaths). Excess deaths were only observed in those aged 75 years
      and over (15% more deaths than expected for the age group 75 to 84 and 29% for
      those aged 85 or over). This phenomenon (heat-associated excess mortality) is an
      emerging public health problem because of its increasing attributable risk, the
      aging of the Spanish population and its forecasted increasing frequency due to
      global warming. The implementation of alert and response systems based on
      monitoring of climate-related risks, emergency room activity and mortality, and
      strengthening the response capacity of the social and health services should be
      considered.

PMID- 16088047
TI  - Summary of the mortality impact assessment of the 2003 heat wave in France.
AB  - France experienced a record-breaking heat wave between 2 and 15 August 2003. All
      the French regions were affected by this heat wave, which resulted in an excess
      of 14 800 deaths between 1 and 20 August. The increase in the number of excess
      deaths followed the same pattern as the increase in temperatures. No deviance
      from the normal death rate was observed in the month of August during the last
      third of the month, nor during the following three months. There was a clear
      discrepancy in the impact of the heat wave from city to city. If the effect of
      duration of consecutive days with high minimal temperatures and deviance with the
      seasonal normal temperature was patent, this could not explain all of the
      observed variability of the death incidence. The victims were mainly elderly
      women older than 75 years. In terms of relative risk and contribution to the
      global toll, deaths linked to heat were the most important. Based on these
      results, the French government developed a Heat Health Watch Warning System and
      set up a preventive action plan for each region in 2004.

PMID- 16088048
TI  - Mortality in Portugal associated with the heat wave of August 2003: early
      estimation of effect, using a rapid method.
AB  - During the first two weeks of August 2003, Portugal was affected by a severe heat
      wave. Following the identification in Portugal of the influence of heat waves on
      mortality in 1981 and 1991 (estimated excess of about 1900 and 1000 deaths
      respectively), the Observatorio Nacional de Saude (ONSA) - Instituto Nacional de
      Saude Dr. Ricardo Jorge, together with the Vigilancia Previsao e Informacao -
      Instituto de Meteorologia, created a surveillance system called iCARO, which has
      been in operation since 1999. iCARO identifies heat waves with potential
      influence on mortality [1]. Before the end of the 2003 heat wave, ONSA had
      produced a preliminary estimate of its effect on mortality. The results based on
      daily number of deaths from 1 June to 12 August 2003 were presented within 4
      working days. Data was gathered from 31 National Civil registrars, covering the
      district capitals of all 18 districts of mainland Portugal, and representing
      approximately 40% of the mainland's mortality. The number of deaths registered in
      the period 30 July to 12 August was compared with the ones registered during 3
      comparison periods: (in July): 1-14 July, 1-28 July, and 15-28 July). 15-28 July,
      the period best resembling the heat wave in time and characteristics, produced an
      estimation of 37.7% higher mortality rate then the value expected under normal
      temperature conditions. From this value, an estimate of 1316 death excess was
      obtained for mainland Portugal. The main purpose of this article is to present
      the method used to identify and assess the occurrence of an effect (excess
      mortality) during the heat wave of summer 2003.

PMID- 16088049
TI  - The 2003 European heat waves.

PMID- 16088050
TI  - Vulnerable populations: lessons learnt from the summer 2003 heat waves in Europe.

PMID- 16088051
TI  - A novel bipolar-drive circuit for medical applications.
AB  - A novel drive circuit, useful for medical electronics, is capable of supplying a
      sample of human tissue, across which there should be zero direct voltage (dc),
      with a well-defined test current from a source having an output impedance
      exceeding 16 MOmega at 100 kHz.

PMID- 16088052
TI  - Wavelet transforms and the ECG: a review.
AB  - The wavelet transform has emerged over recent years as a powerful time-frequency
      analysis and signal coding tool favoured for the interrogation of complex
      nonstationary signals. Its application to biosignal processing has been at the
      forefront of these developments where it has been found particularly useful in
      the study of these, often problematic, signals: none more so than the ECG. In
      this review, the emerging role of the wavelet transform in the interrogation of
      the ECG is discussed in detail, where both the continuous and the discrete
      transform are considered in turn.

PMID- 16088053
TI  - Improved fibre optic respiratory monitoring using a figure-of-eight coil.
AB  - The macro-bending loss effect in optical fibres has been used to redevelop a
      sensor for the measurement of thoracic and abdominal circumferences in non
      invasive respiratory monitoring. The new sensor uses a novel figure-of-eight loop
      configuration, which results in increased linearity of response, less mechanical
      resistance and hysteresis, as well as other benefits. The performance of the new
      sensor as applied to respiratory monitoring is examined, and indicates a higher
      resolution and sensitivity than the old. This enhanced performance enables
      measurement of respiratory and cardiac function using the same transducing fibre.

PMID- 16088054
TI  - Statistical analysis of the DIAMOND MI study by the multipole method.
AB  - We present a new method to describe the dynamics of the beat-to-beat RR time
      series. The classification of the phase-space plots obtained from RR time series
      is performed by a calculation of parameters which describe the features of the
      two-dimensional plot. We demonstrate that every parameter has its specific
      consequence on the evaluation of the state of the cardiac function. By applying
      the method to the DIAMOND MI study we demonstrate that these parameters have more
      prognostic power than previously suggested risk markers. The results suggest that
      the RR intervals constitute a highly complex time series which necessitates the
      use of refined mathematical-statistical methods in order to reveal pathologies in
      the heart rate.

PMID- 16088055
TI  - Digital pulse contour analysis: investigating age-dependent indices of arterial
      compliance.
AB  - The resting peripheral volume pulse wave of 44 subjects within three age
      categories (30-39, 40-49, 50) has been characterized using a novel algorithm for
      the automated determination of a mean pulse function. The contour of this resting
      mean pulse has been analyzed with regard to its systolic and diastolic
      characteristics. Previously described indices of arterial stiffness and
      viscoelasticity have been investigated for age-dependent variations associated
      with arterial mechanical properties. Measures of the minimum rise time (MRT) and
      the stiffness index (SI) demonstrated strong correlations with age and each
      other, although their derivations are unrelated. While significant correlations
      existed (|r| = 0.50-0.78, p < or = 0.002), pairwise comparisons between the right
      and left hands did not demonstrate significant differences for the minimum rise
      time parameter; however, the stiffness index was significantly lower in the left
      hand versus the right (p = 0.009). With regard to age, the youngest age group had
      significantly lower MRT and SI values than the two older groups. For these data,
      this was only demonstrated in parameters calculated for the right hand because of
      higher variability within age groups for the left hand. A normalized average mean
      pulse for each age group was determined which visually illustrated the contour
      changes associated with the MRT and SI parameters that occur in both the systolic
      and diastolic portions of the pulse. The finding that differences between the age
      groups were significantly more evident for the right hand suggests that the
      physical site for such testing may be an important consideration. This study
      provides further evidence regarding the merit of using contour analysis when
      assessing the peripheral volume pulse and the importance of establishing ageing
      indices for such analysis.

PMID- 16088056
TI  - An epileptic seizure prediction algorithm based on second-order complexity
      measure.
AB  - The quality of life of many epilepsy patients may be improved significantly if
      the occurrence of epileptic seizures can be successfully forecasted and clinical
      intervention, such as electrical stimulation or drug delivery, can then be used
      to suppress their emergence, or warn the patient of the forthcoming events. In
      this paper, a prediction algorithm based on the second-order complexity measure
      was proposed to predict the impending seizures. Through the analysis of long-term
      intracranial EEG recordings from two frontal lobe epilepsy patients, the results
      indicated that the sensitivity of prediction was 77.8% (14/18) and 66.7% (4/6)
      and the number of false warnings was 3 and 2 for the two patients, respectively.
      Because only the information of past seizures was utilized to predict the current
      seizure and the computation load was low, the prediction algorithm could possibly
      be applied to clinical practice.

PMID- 16088057
TI  - The dielectric properties of the cranial skin of five young captive Steller sea
      lions (Eumetopias jubatus), and a similar number of young domestic pigs (Sus
      scrofa) and sheep (Ovis aries) between 0.1 and 10 GHz.
AB  - To aid in the development of a long-range subcutaneous radio frequency
      identification tag to monitor the fate of sea lion pups, the dielectric
      properties of the cranial skin of young female otariids, and possible test
      subjects of similar size and age, or pigs (Sus scrofa) and sheep (Ovis aries)
      were obtained over a frequency range of 0.1-10 GHz at the base of their heads
      where the tag will be implanted. The resulting curves were similar in shape to
      adult human skin data, but the values were generally lower. Between subjects,
      variations were noted in all the species. Circuitry for the RF-ID tag is being
      designed to account for antenna detuning as a result of the lossy media or skin
      and the variation in dielectric properties.

PMID- 16088058
TI  - A template matching algorithm for sperm tracking and classification.
AB  - The conventional assessment of human semen, especially sperm movement
      characteristics, is a highly subjective assessment, with considerable intra- and
      inter-technician variability. Computer-assisted sperm analysis (CASA) systems
      provide a rapid and automated assessment of the parameters of sperm motion,
      together with improved standardization and quality control. However, it should be
      noted that the measurement of the sperm head motion by CASA is sensitive to the
      technique of experimentation. While conventional CASA systems use digital
      microscopes with phase-contrast accessories that make the sperm's head appear
      brighter and sharper than the other parts, in this research, a regular light
      microscope was used with a digital camera directly attached to its eyepiece. One
      of the drawbacks of this method is that the images lack proper contrast and
      sharpness. To remedy this, we have proposed an algorithm for sperm tracking that
      is insensitive to image acquisition conditions. This tracking algorithm was used
      after the background and extra particles were successfully removed through a two
      step enhancement algorithm. Additionally, in this research, a template matching
      method was used for finding the sperm's path. Upon examination, it was proven
      that our tracking algorithm worked well with different image acquisition
      conditions. This paper explains how this method reduces error probability in
      finding and tracking sperm in various frames.

PMID- 16088059
TI  - Application of threshold-based acceleration change index (TACI) in heart rate
      variability analysis.
AB  - Heart rate variability (HRV) analysis is a non-invasive and reliable means to
      assess an autonomic nervous system (ANS) function. Heart rate is a non-stationary
      signal that may contain indicators of current diseases and sometimes warnings
      about impending diseases. In this paper, we have proposed the threshold-based
      acceleration change index (TACI) for HRV analysis, which is calculated from the
      sign of differences of RR time series characterizing the dynamics of threshold
      crossings. It was found that TACI is robust in classifying various groups under
      different physiological and pathological conditions. We have studied the behavior
      of TACI for simulated time series (uncorrelated random data, sinusoidal time
      series and logistics map time series) and its robustness in the presence of
      artifacts for RR time series. The performance of TACI is evaluated for
      classifying normal sinus rhythm (NSR), congestive heart failure (CHF) and atrial
      fibrillation (AF). An unpaired Student's t-test was used to check significant
      differences between these groups and the degree of separation between these
      groups was quantified by using the area of a receiver operator curve.

PMID- 16088060
TI  - Trabecular thickness measurement in cancellous bones: postmortem rat studies with
      the zoom-in micro-tomography technique.
AB  - Using the cross-sectional images taken with the zoom-in micro-tomography
      technique, we measured trabecular thicknesses of femur bones in postmortem rats.
      Since the zoom-in micro-tomography technique is capable of high resolution
      imaging of a small local region inside a large subject, we were able to measure
      the trabecular thickness without extracting bone samples from the rats. For the
      zoom-in micro-tomography, we used a micro-tomography system consisting of a micro
      focus x-ray source, a 1248 x 1248 flat-panel x-ray detector and a precision scan
      mechanism. To compensate for the limited spatial resolution in the zoom-in micro
      tomography images, we used the fuzzy distance transform for the calculation of
      the trabecular thickness. To validate the trabecular thickness measurement with
      the zoom-in micro-tomography images, we compared the measurement results with
      those obtained from the conventional micro-tomography images of the extracted
      bone samples. The difference between the two types of measurement results was
      less than 2.5%.

PMID- 16088061
TI  - Application of the 'pull-off' force method for measurement of surface tension of
      upper airway mucosal lining liquid.
AB  - Upper airway luminal patency is influenced by a number of factors including:
      intraluminal air pressure, upper airway dilator muscle activity, surrounding
      extraluminal tissue pressure and surface tension acting within the liquid layer
      lining the upper airway. In this study we examine the performance characteristics
      for the 'pull-off' force method for measuring the surface tension (gamma) of
      liquids. This method is then used to examine the gamma of the liquid lining the
      oro-pharynx in awake human subjects. The gamma of UAL samples (approximately 0.2
      microL) obtained from the posterior pharyngeal wall was quantified using the pull
      off force technique in which gamma is measured as the force required to separate
      two curved silica discs bridged by the liquid sample. Pull-off force measurement
      was not influenced by sample volumes or under different temperature or humidity
      conditions. The coefficients of variation for repeated measurements using the
      pull-off force technique for the three standard liquids ranged from 1.2% to 5.6%.
      The pull-off method tended to give slightly lower values than the Wihelmy balance
      method with the mean difference being 2.4 +/- 1.8 mN m(-1). For the group, the
      gamma of saliva was 59.2 +/- 0.6 mN m(-1) (CV 4.9 +/- 0.9%) for five measurements
      of a single sample. There was no significant relationship between the measured
      gamma values for five subjects measured on five separate days and the day of
      collection of the sample for any of the subjects or the group as a whole (both p
      > 0.6). There was no significant difference (p = 0.53, ANOVA) between the gamma
      values for samples obtained from under the tongue (61.6 +/- 1.7 mN m(-1)), at the
      oral surface of the soft palate (56.1 +/- 3.2 mN m(-1)) and from the posterior
      oro-pharyngeal wall (58.1 +/- 2.4 mN m(-1)). The pull-off force method provides
      adequate reproducibility to be able to measure the gamma of UAL. In healthy
      humans the gamma of UAL is similar to that of saliva.

PMID- 16088062
TI  - Comparison of three different kinematic sensor assemblies for locomotion study.
AB  - The decrease in the costs of electronic components and devices, conjugated to the
      advancement of the miniaturization technologies, has promoted a large profusion
      of the use of motion sensors for human movement analysis in clinics. The errors
      in the design are numerous, from circuital errors to positioning and orientation
      errors; a preliminary approach to the problem by means of simulations is
      necessary. We developed an environment for the simulation of mixed kinematic
      sensor assemblies with accelerometers and rate gyroscopes; it was tested by means
      of three different assemblies in the simulation of the trajectory reconstruction.
      The first assembly was represented by a 6-accelerometer assembly, the second by a
      9-accelerometer assembly and the third was based on three rate gyroscopes and
      three accelerometers. The circuital error, given as an input to the environment,
      was determined during a bench test, the positioning error was set to p(e) = 5 x
      10(-4) m and the orientation error to alpha(e) = 6 x 10(-2) deg. Results showed
      the agreement between estimated and experimental data from the bench test.
      Simulation results also showed that the errors in trajectory reconstruction in
      the sagittal plane were lower than 3-4% during 4 s of simulation.

PMID- 16088063
TI  - Assessment of ECG frequency and morphology parameters for automatic
      classification of life-threatening cardiac arrhythmias.
AB  - The reliable recognition and adequate electrical shock therapy of life
      threatening cardiac states depend on the electrocardiogram (ECG) descriptors
      which are used by the defibrillator-embedded automatic arrhythmia analysis
      algorithms. We propose a method for real-time ECG processing and parameter set
      extraction using band-pass digital filtration and ECG peak detection. Twelve
      parameters were derived: (i) seven parameters from the band-pass filter output
      six threshold parameters and one peak counter; (ii) five parameters from the ECG
      peak detection branch, which assess the heart rate, the periodicity and the
      amplitude/slope symmetry of the ECG peaks. The statistical assessment for more
      than 36 h of cardiac arrhythmia episodes collected from the public AHA and MIT
      databases showed that some of the parameters achieved high specificity and
      sensitivity, but there was no parameter providing 100% separation between non
      shockable and shockable rhythms. In order to estimate the influence of the wide
      variety of cardiac arrhythmias and the different artifacts in real recording
      conditions, we performed a more detailed study for eight non-shockable and four
      shockable rhythm categories. The combination of the six top-ranked parameters
      provided specificity: (i) more than 99% for rhythms with narrow supraventricular
      complexes, premature ventricular contractions, paced beats and bradycardias; (ii)
      almost 95% for supraventricular tachycardias; (iii) 91.5% for bundle branch
      blocks; (iv) 92.2% for slow ventricular tachycardias. The attained sensitivity
      was above 98% for coarse and fine ventricular fibrillations and 94% for the rapid
      ventricular tachycardias. The accuracy for the noise contaminated non-shockable
      and shockable signals exceeded 93%. The proposed parameter set guarantees an
      accuracy that meets the AHA performance goal for each rhythm category and could
      be a reliable facility for AED shock-advisory algorithms.

PMID- 16088064
TI  - High spontaneous fluctuation in arterial blood pressure improves the assessment
      of cerebral autoregulation.
AB  - Cerebral autoregulation maintains a relatively constant blood flow despite
      changes of blood pressure in the brain. Linear models have been extensively
      applied to identify this mechanism, using spontaneous arterial blood pressure
      (ABP) fluctuation as input and cerebral blood flow velocity (CBFV) change as
      output. Although valuable measurements have been achieved by these models,
      accuracy and consistency are of great concern due to the large variability of
      results. We therefore investigated whether more reliable measurements can be
      achieved by selecting only those recordings (or parts of recordings) with
      relatively high spontaneous variability of ABP. Twenty-four recordings, 7 from
      hypercapnia and 17 from normocapnia, of ABP and CBFV from 9 healthy adults were
      analyzed. Two conventional autoregulatory parameters were used to assess cerebral
      autoregulation. In the absence of a 'gold' standard for the study of dynamic
      cerebral autoregulation, lower variability of the parameters and higher
      correlation with pCO(2) were considered as criteria for identifying improved
      measures of autoregulation. Both significantly lower variability of the
      parameters, and higher correlation between the parameters and pCO(2) were
      achieved from the data with higher variability of blood pressure. We therefore
      conclude that ABP with high variability may effectively stimulate regulatory
      response in blood flow resulting in improved assessment of cerebral
      autoregulation.

PMID- 16088065
TI  - High-resolution QRS fiducial point corrections in sparsely sampled ECG
      recordings.
AB  - A model based high-resolution QRS fiducial point correction algorithm, which is
      suitable for sparsely sampled electrocardiogram (ECG) recordings, is presented.
      The presented method can be divided into three steps. First, the initial QRS
      fiducial points are estimated by using ordinary interpolation methods. Then, the
      data points of each QRS are extracted and centered in time and the shape of the
      QRS complex is estimated by nonlinearly fitting a double exponential function to
      the extracted data points. Finally, the estimated model and its derivative are
      linearly fitted to the data points of each QRS complex separately and new
      fiducial point estimates are obtained. The proposed method is tested with
      simulations and real ECG data. As a result, it is observed that the proposed
      method is also suitable for asymmetric QRS complexes unlike, e.g., the commonly
      used cubic spline interpolation method.

PMID- 16088066
TI  - Quantitative analysis of contraction patterns in electrical activity signal of
      pregnant uterus as an alternative to mechanical approach.
AB  - Monitoring of uterine contraction activity is an important diagnostic tool used
      during both pregnancy and labour. The strain the pregnant uterus exerts on the
      maternal abdomen is measured via external tocography. However, limitation of this
      approach has caused the development of another technique-electrohysterography-
      which is based on the recording of electrical uterine activity. A computer-aided
      system is presented, which allows the recording of electrohysterographic signals
      from the maternal abdomen and their on-line analysis both in time and frequency
      domains. As a research material, we acquired 108 traces during a 24 h period
      before labour from a group of patients between 37 and 40 weeks of gestation. The
      comparison study between electrohysterography and tocography was carried out
      thanks to the possibility of simultaneous recording of mechanical and electrical
      uterine activities. The obtained results show that both methods demonstrate high
      agreement in relation to the number of contractions recognized as being
      consistent. However, their agreement in relation to the quantitative description
      of recognized patterns has appeared to be unacceptable to consider these methods
      as fully alternative. The appropriate way of further development of
      electrohysterography seems to be spectral analysis. Several spectral parameters
      describing electrophysiological properties of uterine muscle can be obtained by
      the use of electrohysterographic signals.

PMID- 16088067
TI  - Thawing of frozen calcaneus bone specimens has no effect on the bone mineral
      density using dual energy x-ray absorptiometry: a study in rabbits and humans.
AB  - The purpose of this paper is to study whether the deep freezing of bone and later
      thawing affects the bone mineral density (BMD) measurement. We used 56 calcanei
      from 28 adult female New Zealand white rabbits and 102 human calcanei from 51
      donors post-mortem (27 men and 24 women, age 30-89). Dual energy x-ray
      absorptiometry evaluated BMD of the frozen specimen and of the thawed specimen. A
      main analysis compared BMD of each specimen in the frozen and thawed states. The
      mean BMD of 224 areas of frozen rabbits' calcanei was 0.31 +/- 0.08 g cm(-2) (95%
      confidence interval (CI) from 0.30 to 0.32 g cm(-2)) while the mean BMD of thawed
      rabbits' calcanei was 0.31 +/- 0.08 g cm(-2) (95% CI from 0.30 to 0.32 g cm(-2);
      paired t-test p > 0.01). The mean BMD of 306 areas of frozen human calcaneus was
      0.73 +/- 0.22 g cm(-2) (95% CI from 0.70 to 0.76 g cm(-2)) while the mean BMD of
      thawed human calcaneus was 0.73 +/- 0.22 g cm(-2) (95% CI from 0.70 to 0.76 g cm(
      2); p > 0.01). For both the rabbit and the human calcanei, a Bland-Altman
      analysis showed a mean difference between the BMD in the frozen and thawed states
      of 0.00 (limits of agreement, rabbit: -0.07 to 0.08 g cm(-2), human: -0.16 to
      0.21 g cm(-2)). A high correlation was observed between calcaneus BMD in the
      frozen and thawed states (r = 0.94, 0.97, 0.92 and 0.99 respectively in all
      rabbit calcanei, all human calcanei, immobilized rabbit calcanei and osteopenic
      human calcanei, all p < 0.01). Bone mineral density is not affected by deep
      freezing and later thawing of the specimen. Therefore, the specimens need not be
      thawed to obtain valid and precise BMD measurement. These results are relevant to
      general musculoskeletal as well as osteoporosis research where the specimens
      undergo multiple tests in series.

PMID- 16088068
TI  - Pitch jump probability measures for the analysis of snoring sounds in apnea.
AB  - Obstructive sleep apnea (OSA) is a highly prevalent disease in which upper
      airways are collapsed during sleep, leading to serious consequences. The gold
      standard of diagnosis, called polysomnography (PSG), requires a full-night
      hospital stay connected to over ten channels of measurements requiring physical
      contact with sensors. PSG is inconvenient, expensive and unsuited for community
      screening. Snoring is the earliest symptom of OSA, but its potential in clinical
      diagnosis is not fully recognized yet. Diagnostic systems intent on using snore
      related sounds (SRS) face the tough problem of how to define a snore. In this
      paper, we present a working definition of a snore, and propose algorithms to
      segment SRS into classes of pure breathing, silence and voiced/unvoiced snores.
      We propose a novel feature termed the 'intra-snore-pitch-jump' (ISPJ) to diagnose
      OSA. Working on clinical data, we show that ISPJ delivers OSA detection
      sensitivities of 86-100% while holding specificity at 50-80%. These numbers
      indicate that snore sounds and the ISPJ have the potential to be good candidates
      for a take-home device for OSA screening. Snore sounds have the significant
      advantage in that they can be conveniently acquired with low-cost non-contact
      equipment. The segmentation results presented in this paper have been derived
      using data from eight patients as the training set and another eight patients as
      the testing set. ISPJ-based OSA detection results have been derived using
      training data from 16 subjects and testing data from 29 subjects.

PMID- 16088069
TI  - Coherence between oxygen saturation and heart rate obtained from pulse oximetric
      recordings in obstructive sleep apnoea.
AB  - In obstructive sleep apnoea (OSA) cyclical changes in oxygen saturation and heart
      rate in the period range of 30-120 s are observed. In these patients, we
      prospectively analyse the coherence of nocturnal SaO(2) and heart rate signals. A
      sample of 201 clinically suspected of having OSA were studied using nocturnal
      pulse oximetric and complete polysomnography. Coherence function versus period
      curves were categorized into three patterns: a positive pattern showing a
      predominant positive peak value of coherence in the period range of 30-120 s; a
      negative pattern if the predominant coherence was negative in the same range; and
      an undetermined pattern if no predominance was detected. One hundred and thirteen
      patients present a positive coherence pattern; 74.3% of these have OSA. A
      negative coherence pattern was observed for 28 patients; 85.7% of these have OSA.
      The remaining 60 patients present an undetermined pattern. Patients with OSA
      presented significantly higher maximal positive coherence and maximal negative
      coherence than those without OSA. We conclude that OSA patients present dynamic
      coordination and interdependence between SaO(2) and heart rate in specific
      frequencies.

PMID- 16088070
TI  - Photoplethysmography detection of lower limb peripheral arterial occlusive
      disease: a comparison of pulse timing, amplitude and shape characteristics.
AB  - The assessment and diagnosis of lower limb peripheral arterial occlusive disease
      (PAOD) is important since it can lead progressively to disabling claudication,
      ischaemic rest pain and gangrene. Historically, the first assessment has been
      palpation of the peripheral pulse since it can become damped, delayed and
      diminished with disease. In this study we investigated the clinical value of
      objective photoplethysmography (PPG) pulse measurements collected simultaneously
      from the right and left great toes to diagnose disease in the lower limbs. In
      total, 63 healthy subjects and 44 patients with suspected lower limb disease were
      studied. Pulse wave analysis techniques extracted timing, amplitude and shape
      characteristics for both toes and for right-to-left toe differences. Normative
      ranges of pulse characteristics were then calculated for the healthy subject
      group. The relative diagnostic values of the different pulse features for
      detecting lower limb arterial disease were determined, referenced to the
      established ankle-brachial pressure index (ABPI) measurement. The ranges of pulse
      characteristics and degree of bilateral similarity in healthy subjects were
      established, and the degrees of pulse delay, amplitude reduction, and damping and
      bilateral asymmetry were quantified for different grades of disease. When pulse
      timing, amplitude and shape features were ranked in order of diagnostic
      performance, the shape index (SI) gave substantial agreement with ABPI (>90%
      accuracy, kappa 0.75). SI also detected higher grade disease, for legs with an
      ABPI less than 0.5, with a sensitivity of 100%. The simple-to-calculate timing
      differences between pulse peaks produced a diagnostic accuracy of 88% for all
      grades of arterial disease (kappa 0.70), and 93% for higher grade disease (kappa
      0.77). These contrasted with the limited discriminatory value of PPG pulse
      amplitude. The low-cost and simplicity of this optical-based technology could
      offer significant benefits to healthcare, such as in primary care where non
      invasive, accurate and simple-to-use (de-skilled) diagnostic techniques are
      desirable.

PMID- 16088071
TI  - A new technique for evaluating sphincter function in visceral organs: application
      of the functional lumen imaging probe (FLIP) for the evaluation of the oesophago
      gastric junction.
AB  - No quantitative method has been implemented routinely in clinical practice to
      assess the oesophago-gastric junction (OGJ). Using impedance planimetry a
      functional lumen imaging probe (FLIP) was constructed to measure eight cross
      sectional areas (CSA) at 4 mm intervals inside a saline-filled bag. To validate
      the FLIP technique for profiling the OGJ, polymethylmethacrylate (Perspex)
      cylinders with different CSAs were measured ten times by the FLIP to assess
      reproducibility and accuracy. A geometric sphincter phantom was constructed and
      its geometry was measured with a 360 degrees radial ultrasound (US) mini-probe
      pulled through it at a rate of 1 mm s(-1). The measurements were compared with
      FLIP measurements. Safety and technique reproducibility were tested on a
      volunteer. Reproducibility and accuracy between the ten samples were good. The
      probe performed well with and without a balloon mounted on it except for the
      smallest CSA (38.5 mm(2)) where there was a difference of 22% from the actual
      value at one CSA measurement point. The FLIP imaged the phantom geometry as well
      as the radial scanning US mini-probe. Pilot studies on a volunteer showed that
      the probe could be placed in the OGJ and the balloon distensions revealed the
      geometry of the sphincter at various levels of distension. The technique may be
      useful in accessing the role of the OGJ in diseases such as gastroesophageal
      reflux disease (GORD) and achalasia and their treatments with surgical and
      endoscopic therapies.

PMID- 16088072
TI  - What affects esophageal injury during radiofrequency ablation of the left atrium?
      An engineering study based on finite-element analysis.
AB  - Recent studies on intraoperative radiofrequency ablation of atrial fibrillation
      have reported some cases of injury to the esophagus. The aim of this study was to
      perform computer simulations using a theoretical model in order to investigate
      the effect of different factors on the temperature distributions in the esophagus
      during ablation. A three-dimensional model was built to include an active
      electrode, atrial tissue, epicardial fat layer and a fragment of esophagus, aorta
      and lung, all linked by connective tissue. The finite-element method was used to
      calculate the temperature distribution during a procedure of constant-temperature
      ablation. The lesion geometry was assessed using a 50 degrees C isotherm. Our
      results show that the electrical power directly applied to the esophagus is
      insignificant and hence the esophageal injury is exclusively due to thermal
      conduction from the atrium. The esophageal lesion is mainly influenced by the
      thickness of connective tissue. Both the programmed target temperature of the
      electrode and the duration of the ablation also have a significant effect on the
      lesion in the esophagus. In contrast, the epicardial fat layer (0.9 mm thickness)
      did not show a significant influence. In conclusion, this theoretical model
      allows us to study the effect of different factors on the thermal injury in the
      esophagus during intraoperative radiofrequency ablation of atrial tissue.

PMID- 16088073
TI  - Spectroscopy study of the dynamics of the transencephalic electrical impedance in
      the perinatal brain during hypoxia.
AB  - Hypoxia/ischaemia is the most common cause of brain damage in neonates. Thousands
      of newborn children suffer from perinatal asphyxia every year. The cells go
      through a response mechanism during hypoxia/ischaemia, to maintain the cellular
      viability and, as a response to the hypoxic/ischaemic insult, the composition and
      the structure of the cellular environment are altered. The alterations in the
      ionic concentration of the intra- and extracellular and the consequent cytotoxic
      oedema, cell swelling, modify the electrical properties of the constituted
      tissue. The changes produced can be easily measured using electrical impedance
      instrumentation. In this paper, we report the results from an impedance
      spectroscopy study on the effects of the hypoxia on the perinatal brain. The
      transencephalic impedance, both resistance and reactance, was measured in newborn
      piglets using the four-electrode method in the frequency range from 20 kHz to 750
      kHz and the experimental results were compared with numerical results from a
      simulation of a suspension of cells during cell swelling. The experimental
      results make clear the frequency dependence of the bioelectrical impedance,
      confirm that the variation of resistance is more sensitive at low than at high
      frequencies and show that the reactance changes substantially during hypoxia. The
      resemblance between the experimental and numerical results proves the validity of
      modelling tissue as a suspension of cells and confirms the importance of the
      cellular oedema process in the alterations of the electrical properties of
      biological tissue. The study of the effects of hypoxia/ischaemia in the
      bioelectrical properties of tissue may lead to the development of useful clinical
      tools based on the application of bioelectrical impedance technology.

PMID- 16088074
TI  - Bilateral photoplethysmography studies of the leg arterial stenosis.
AB  - A newly developed portable multi-channel photoplethysmography (PPG) device has
      been used for comparative studies of 20 healthy control subjects and 45 patients
      with diagnosed arterial stenosis in a leg. The peripheral blood pulsations were
      detected simultaneously at four body sites-the same fingers and toes of both arms
      and legs. The PPG pulses recorded at the periphery of the stenotic leg, if
      compared with those of the healthy leg, were much weaker, with delayed arrival as
      a consequence of increased pulse wave transit time (PWTT) due to higher vascular
      resistance. The specific PWTT delays for the occluded legs were in the range of
      20-80 ms, while in the case of healthy subjects the leg PPG signals arrived
      without delays or with smaller time-shifts not exceeding 14 ms. The reference
      bilateral PPG signals detected at the fingertips did not show any notable PWTT
      delays in both groups. Parallel measurements of local blood pressures by means of
      the oscillometry method with subsequent calculation of the ankle-brachial index
      were performed. Convincing correlation between the bilateral differences in the
      local blood pressure (a routine tool for diagnostics of leg stenosis) and in the
      corresponding PWTT delay (Pearson's coefficient r = 0.93), as well as between the
      PWTT delay and the ankle-brachial index (r = -0.96) has been established. From
      the point of view of PWTT delay, the average value of leg stenosis diagnostic
      threshold was established to be in the range of 23 +/- 9 ms, with full
      reliability above 32 ms. The obtained data may find further applications in
      alternative methodologies for detection and/or assessment of arterial occlusions
      in human extremities.

PMID- 16088075
TI  - Noise analysis in magnetic resonance electrical impedance tomography at 3 and 11
      T field strengths.
AB  - In magnetic resonance electrical impedance tomography (MREIT), we measure the
      induced magnetic flux density inside an object subject to an externally injected
      current. This magnetic flux density is contaminated with noise, which ultimately
      limits the quality of reconstructed conductivity and current density images. By
      analysing and experimentally verifying the amount of noise in images gathered
      from two MREIT systems, we found that a carefully designed MREIT study will be
      able to reduce noise levels below 0.25 and 0.05 nT at main magnetic field
      strengths of 3 and 11 T, respectively, at a voxel size of 3 x 3 x 3 mm(3).
      Further noise level reductions can be achieved by optimizing MREIT pulse
      sequences and using signal averaging. We suggest two different methods to
      estimate magnetic flux noise levels, and the results are compared to validate the
      experimental setup of an MREIT system.

PMID- 16088076
TI  - Exercise training in patients receiving maintenance hemodialysis: a systematic
      review of clinical trials.
AB  - BACKGROUND: Exercise is not routinely advocated in patients with end-stage renal
      disease (ESRD) receiving maintenance hemodialysis (HD), compared to best practice
      in other chronically diseased cohorts. Lack of widespread awareness of the
      exercise in HD literature may be contributing to these shortcomings of clinical
      practice. Therefore, our objectives are: (1) to systematically review trials of
      exercise training involving adult HD patients; (2) to provide empirical evidence
      that exercise can elicit health-related adaptations in this cohort, and (3) to
      provide recommendations for future investigations. METHOD: A systematic review of
      the literature using computerized databases was performed. RESULTS: According to
      the 29 trials reviewed, HD patients can safely derive a myriad of health-related
      adaptations from engaging in appropriately structured exercise regimens involving
      aerobic and/or resistance training. However, methodological limitations within
      this body of literature may be partially responsible for minimal advocacy for
      exercise in this cohort. CONCLUSIONS: Robustly designed RCTs with thorough,
      standardized reporting are required if clinical practice and quality of life of
      this cohort is to be enhanced through the integration of exercise training and
      mainstream medical practice. Future trials should demonstrate the clinical
      importance, and long-term feasibility and applicability of exercise training for
      this vulnerable patient population.

PMID- 16088077
TI  - Chemokine receptor CCR1: a new target for progressive kidney disease.
AB  - Infiltrating leukocytes are thought to contribute to the progression of kidney
      disease. Locally produced chemokines guide circulating leukocytes into the
      kidney, which renders therapeutic blockade of respective chemokine receptors on
      the leukocyte surface as potential targets for the inhibition of renal leukocyte
      recruitment. By using mutant mice and specific antagonists, we found that
      chemokine receptor CCR1 has non-redundant functions for leukocyte adhesion to
      activated vascular endothelium and for transendothelial diapedesis. Most
      importantly, CCR1 blockade with a specific small molecule antagonist can improve
      injury in several types of progressive kidney disease models, even if treatment
      is initiated in advanced disease states. Identification of new targets may add to
      the therapeutic options in chronic kidney disease.

PMID- 16088078
TI  - CD2AP expression in a renal ischemia/reperfusion injury model and analysis of its
      related genes using overexpression and RNA interference technique.
AB  - BACKGROUND: CD2-associated protein (CD2AP) is a ubiquitously expressed 80-kDa
      intracellular protein, and has been speculated to act as an intracellular
      signaling pathway between plasma membrane proteins and cytoskeleton proteins.
      CD2AP expression has been reported in both the glomerulus and tubular epithelium
      in the kidney, and CD2AP knockout mice exhibit congenital nephrotic syndrome.
      However, the precise properties and its role in the renal tubules have not been
      clarified. METHODS: We used an established rat model of ischemic/reperfusion
      renal injury (IRI) to examine the expression of CD2AP by real-time PCR, Western
      blotting, and immunohistochemistry. We also investigated the expression of genes
      related to apoptosis and cell proliferation in mouse collecting duct-derived
      cells (M1 cells) transfected with full-length of CD2AP cDNA or short interfering
      RNA. RESULTS: CD2AP mRNA and protein expression had significantly increased in
      the IRI kidney. Real-time PCR indicated that expression of genes regulating
      apoptosis, such as B-Raf and Caspase-12, and genes regulating cell proliferation
      factors, CDC2, was decreased in CD2AP-overexpressing M1 cells and increased in
      CD2AP-interfered M1 cells. CONCLUSIONS: These results suggest that CD2AP
      expression was increased following renal ischemia and that CD2AP may be related
      to the process of cell repair and/or cell differentiation following injury.

PMID- 16088079
TI  - Jejunal dopamine and Na,K+-ATPase activity in nephrotic syndrome.
AB  - BACKGROUND: The occurrence of complementary functions in sodium transport between
      the intestine and the kidney was suggested to occur when the renal function is
      immature or compromised and jejunal dopamine has been implicated in this renal
      intestinal cross-talk. The jejunal sodium transport was not previously evaluated
      in the nephrotic syndrome. METHODS: We examined the jejunal Na(+),K(+)-ATPase
      activity and the role of dopamine in puromycin aminonucleoside (PAN) and HgCl(2)
      induced nephrotic syndrome rat models. RESULTS: In both nephrotic syndrome rat
      models, the jejunal Na(+),K(+)-ATPase activity was reduced during greatest sodium
      retention and ascites accumulation (PAN nephrosis, day 7; HgCl(2) nephrosis, day
      14), whereas during enhanced sodium excretion and ascites mobilization the
      jejunal Na(+),K(+)-ATPase activity was increased in HgCl(2) nephrosis (day 21)
      and was similar to controls in PAN nephrosis (day 14). In both PAN- and HgCl(2)
      induced nephrosis, the jejunal aromatic L-amino acid decarboxylase (AADC)
      activity, the enzyme responsible for the synthesis of jejunal dopamine, did not
      differ from controls. In addition, the jejunal Na(+),K(+)-ATPase activity was not
      sensitive to inhibition by dopamine (1 microM) in both experimental groups
      throughout the study. CONCLUSIONS: In the nephrotic syndrome the jejunal
      Na(+),K(+)-ATPase activity may respond in a compensatory way to changes in
      extracellular volume, through dopamine-independent mechanisms.

PMID- 16088080
TI  - Angiotensin receptor blockade and arterial compliance in chronic kidney disease:
      a pilot study.
AB  - BACKGROUND: Almost 20 million people in the US have chronic kidney disease (CKD).
      Cardiovascular disease and arterial wall abnormalities are common in this
      population. Because angiotensin II may have adverse effects on the arterial wall,
      we hypothesized that an angiotensin receptor blocker (ARB) would improve arterial
      compliance as compared with placebo in subjects with CKD. METHODS: We performed a
      double-blinded, placebo-controlled pilot study in which 25 subjects with stages 2
      or 3 CKD and proteinuria <1 g were randomized to either the ARB, eprosartan, or
      placebo and titrated to achieve a goal blood pressure (BP) <130/85 mm Hg.
      Arterial compliance was measured at baseline and at 8 weeks. RESULTS: Baseline
      characteristics were similar between the groups and included mean estimated
      glomerular filtration rate 63 +/- 14 ml/min/1.73 m(2), heart rate 76 +/- 10
      beats/min, BP 142 +/- 12/81 +/- 8 mm Hg, 64% diabetic, 44% male, and 40% white,
      though subjects in the eprosartan group were younger (60 +/- 12 vs. 70 +/- 6
      years, p = 0.01). There were no significant differences between the groups in
      large or small artery compliance measurements either at baseline or at 8 weeks,
      but there was a statistically significant improvement from baseline in small
      artery compliance in the eprosartan group (from median 2.5 ml/mm Hg x 100 [90% CI
      (1.1, 4.7)] to 4.0 ml/mm Hg x 100 [90% CI (1.9, 6.7)] (p = 0.01)) not seen in the
      placebo group. CONCLUSION: Use of an ARB to achieve recommended BP is associated
      with improved small artery compliance in people with CKD, though larger studies
      are needed to confirm these findings.

PMID- 16088081
TI  - Pharmacokinetic study of ferumoxytol: a new iron replacement therapy in normal
      subjects and hemodialysis patients.
AB  - BACKGROUND: Currently available intravenous iron preparations are not ideal,
      either because of safety concerns or dose limitations. We investigated the safety
      and pharmacokinetics of ferumoxytol, a new iron replacement therapy, in normal
      subjects and hemodialysis patients. METHODS: In a randomized, double-blind,
      ascending-dose study in normal volunteers (n = 41), 6 subjects received placebo,
      and 8 subjects each received ferumoxytol, at 1, 2 or 4 mg iron/kg, injected at 60
      mg iron/min. The remaining subjects received 4 mg iron/kg at injection rates of
      90 (n = 3), 180 (n = 3) or 1,800 mg iron/min (n = 5). In the second, open-label,
      ascending-dose study, 20 hemodialysis patients received 125 or 250 mg of iron
      over 5 min. RESULTS: In normal subjects, the blood half-life of ferumoxytol
      increased with increasing dose from 9.3 to 14.5 h (p < 0.05) but not with
      increasing rate of injection. The drug half-life in hemodialysis patients was
      similar to normal subjects. Ferumoxytol was not removed with hemodialysis. Serum
      iron (p < 0.001), transferrin saturation (p < 0.001) and ferritin increased in
      both populations. No serious adverse events were attributable to ferumoxytol.
      CONCLUSION: Ferumoxytol was well tolerated in this study. Its pharmacokinetic
      properties and simplicity of administration suggest that it will be an attractive
      form of iron replacement therapy.

PMID- 16088082
TI  - Impaired glomerular and tubular function as a short-term effect of sirolimus
      treatment in the rat.
AB  - AIMS: To investigate acute and short-term effects of sirolimus (SRL) on glomerulo
      tubular function, blood pressure (BP), and renal morphology in the rat. METHODS:
      Male Sprague-Dawley rats, weighing initially 140-180 g were treated with SRL in
      three series: SRL 0.2, 0.4, or 0.8 mg/kg/day intraperitoneally for up to 28 days
      after skin allo-transplantation from Lewis donors (to establish a dosage with
      significant immunosuppressive effect). SRL 0.4 mg/kg intravenously (acute
      effects). SRL 0.4 mg/kg/day intraperitoneally for 7 days (short-term effects).
      Inulin, lithium (C(Li)) and sodium clearance, and intra-arterial BP were measured
      in conscious catheterized rats. Morphological kidney studies were completed after
      post-mortem fixation. RESULTS: Maximum immunosuppressive effect was achieved with
      SRL 0.4 mg/kg/day. SRL acutely increased GFR and C(Li), whereas fractional
      proximal reabsorption (PFR) declined. In the short-term study SRL had opposite
      effects on GFR and C(Li), unaffected proximal tubular reabsorption and PFR,
      raised BP, diminished food consumption, and slower increase in body weight.
      Morphological changes were non-specific. CONCLUSION: In a dosage giving maximum
      immunosuppressive effect, SRL revealed acute effects on glomerular and proximal
      tubular function thus indicating increased outflow from the proximal tubules
      whereas one week of SRL treatment produced a change resembling the known
      nephrotoxic effects of the calcineurine inhibitors.

PMID- 16088083
TI  - The pro children study: conceptualization, baseline results and intervention
      development of a European effort to promote fruit and vegetable consumption in
      schoolchildren.

PMID- 16088084
TI  - Promoting fruit and vegetable consumption among European schoolchildren:
      rationale, conceptualization and design of the pro children project.
AB  - BACKGROUND/AIMS: The Pro Children Project was designed to assess fruit and
      vegetable consumption in European schoolchildren and their parents, as well as
      determinants of the children's consumption patterns. A second objective was to
      develop and test strategies, applicable across Europe, for promoting consumption
      of fruits and vegetables among schoolchildren and their parents. In this paper,
      the rationale, theoretical background, overall design and implementation of the
      project is presented. METHODS: Surveys of national, representative samples of 11
      year-old schoolchildren and their parents were conducted in 9 countries, i.e. in
      Austria, Belgium, Denmark, Iceland, the Netherlands, Norway, Portugal, Spain and
      Sweden. Comprehensive school-based educational programmes have been developed and
      tested in three settings, i.e. in Spain, the Netherlands and in Norway. A
      precoded 24-hour recall form combined with a set of food frequency questions
      assessing regular intake were used to assess fruit and vegetable consumption.
      Determinants were assessed employing a comprehensive theoretical framework
      including personal, social and environmental factors related to fruit and
      vegetable consumption. The intervention programmes have been tested employing a
      group-randomized trial design where schools have been randomly allocated to an
      intervention arm and a delayed intervention arm. Surveys among all participating
      children and their parents were conducted prior to the initiation of the
      intervention, immediately after the end of the intervention and at the end of the
      subsequent school year. CONCLUSION: The project is expected to provide new
      information of great importance for improving our understanding of consumption
      patterns of fruits and vegetables and for guiding future efforts to promote
      increased consumption patterns across Europe.

PMID- 16088085
TI  - Validity and reproducibility of a precoded questionnaire to assess fruit and
      vegetable intake in European 11- to 12-year-old schoolchildren.
AB  - BACKGROUND/AIMS: Validity and reproducibility were evaluated of a new
      questionnaire to assess fruit and vegetable intakes in 11- to 12-year-old
      children. METHODS: The precoded teacher-assisted self-administered questionnaire
      included two sections: a 24-hour recall part and a food frequency part. Validity
      was tested in 4 countries (Denmark, Iceland, Norway, Portugal; n = 43-60 per
      country) using a 1-day weighed food record and 7-day food records as reference
      methods. Test-retest (7-12 days apart) reproducibility was assessed in 6
      countries (Belgium, Denmark, Iceland, Norway, Portugal, Spain; n = 60-74 per
      country). RESULTS: Spearman rank correlations for fruit and vegetable intake
      according to the frequency part and the 7-day food record ranged between r = 0.40
      0.53. Between 25-50% were classified into the same quartile and 70-88% into the
      same or adjacent quartile. Test-retest Spearman rank correlations for the food
      frequency part were r = 0.47-0.84. Three countries showed no significant
      difference between fruit intake as assessed with the 24-hour recall part and the
      1-day weighed food record, and 2 countries showed no significant difference for
      vegetables. In the other countries, the 24-hour recall part resulted in
      substantially higher mean intake levels. CONCLUSION: Validity and reproducibility
      as to ranking of subjects were regarded to be satisfactory in all countries.
      Group mean intake, based on the original 24-hour part, was valid for fruit in 3
      countries and for vegetables in 2 countries, and this part was subsequently
      adjusted to avoid overestimation, before the questionnaire was used in the Pro
      Children study.

PMID- 16088086
TI  - A qualitative exploration of determinants of fruit and vegetable intake among 10-
      and 11-year-old schoolchildren in the low countries.
AB  - BACKGROUND: For the development of fruit and vegetable promotion interventions,
      insight is needed into determinants of health behaviour. This study presents
      results of focus group interviews held with 10- to 11-year-old schoolchildren
      from Ghent (Belgium-Flanders) and Rotterdam (the Netherlands) to explore personal
      beliefs and motivations and environmental factors related to schoolchildren's
      fruit and vegetable intake, to inform the Pro Children intervention development.
      METHODS: Twelve focus groups were held with 92 schoolchildren. The interviews
      were recorded and transcribed and NVivo was used to analyse the transcripts.
      RESULTS: Positive health beliefs, taste preferences, lack of knowledge and
      practical barriers were identified as personal factors related to fruit and
      vegetable intake. Home and school availability of fruits and vegetables, as well
      as parenting practices were identified as important environmental factors.
      CONCLUSION: A fruit and vegetable promotion intervention should aim to increase
      fruit and vegetable accessibility and should include educational and motivational
      activities tailored to these personal and environmental factors. These
      indications should be further evaluated in quantitative research among
      representative samples.

PMID- 16088087
TI  - Fruit and vegetable intake in a sample of 11-year-old children in 9 European
      countries: The Pro Children Cross-sectional Survey.
AB  - BACKGROUND/AIMS: An adequate fruit and vegetable intake provides essential
      nutrients and nutritive compounds and is considered an important part of a
      healthy lifestyle. No simple instrument has been available for the assessment of
      fruit and vegetable intake as well as its determinants in school-aged children
      applicable in different European countries. Within the Pro Children Project, such
      an instrument has been developed. This paper describes the cross-sectional survey
      in 11-year-olds in 9 countries. METHODS: The cross-sectional survey used
      nationally, and in 2 countries regionally, representative samples of schools and
      classes. The questionnaires, including a precoded 24-hour recall component and a
      food frequency part, were completed in the classroom. Data were treated using
      common syntax files for portion sizes and for merging of vegetable types into
      four subgroups. RESULTS: The results show that the fruit and vegetable intake in
      amounts and choice were highly diverse in the 9 participating countries.
      Vegetable intake was in general lower than fruit intake, boys consumed less fruit
      and vegetables than girls did. The highest total intake according to the 24-hour
      recall was found in Austria and Portugal, the lowest in Spain and Iceland.
      CONCLUSION: The fruit and vegetable intake in 11-year-old children was in all
      countries far from reaching population goals and food-based dietary guidelines on
      national and international levels.

PMID- 16088088
TI  - Fruit and vegetable intake of mothers of 11-year-old children in nine European
      countries: The Pro Children Cross-sectional Survey.
AB  - OBJECTIVE: To describe and compare fruit and vegetable intakes of mothers of 11
      year-old children across Europe. METHODS: Cross-sectional surveys were carried
      out in 9 European countries in October/November 2003. Self-administered
      questionnaires assessing fruit and vegetable consumption were used for data
      collection. The current paper presents dietary intake data obtained by a precoded
      24-hour recall and a food frequency questionnaire. RESULTS: The consumption
      levels of fruit and vegetables (without fruit juice) were in line with World
      Health Organization recommendations of > or =400 g/day for only 27% of all
      participating mothers. Based on both instruments, the Pro Children results showed
      comparatively high average fruit intake levels in Portugal, Denmark and Sweden
      (211, 203 and 194 g/day) and the lowest intake in Iceland (97 g/day). High
      vegetable intake levels were found in Portugal and Belgium (169 and 150 g/day),
      the lowest in Spain (88 g/day). A south-north gradient could not be observed in
      the Pro Children study. CONCLUSION: Fruit and vegetable intakes are low in
      mothers of 11-year-olds across Europe. Especially vegetable consumption can be
      regarded as marginal in most of the studied European countries. A high percentage
      of mothers indicated to eat fruit and vegetables less than once a day. The
      results have shown that national and international interventions are necessary to
      promote fruit and especially vegetable consumption in the European population of
      mothers.

PMID- 16088089
TI  - Personal, social and environmental factors regarding fruit and vegetable intake
      among schoolchildren in nine European countries.
AB  - BACKGROUND/AIMS: Children in Europe are consuming less fruit and vegetables than
      recommended. Knowledge about the potential determinants of fruit and vegetable
      intake is vital to understand discrepancies in intake and to guide interventions.
      The aim of the present study was to assess personal, social and environmental
      factors regarding fruit and vegetable intake among 11- to 12-year-old children in
      Europe. METHODS: A cross-sectional survey was undertaken, with nationally or
      regionally representative samples of in total 13,305 children (mean age 11.4
      years) from nine European countries. Pupils in the classroom completed a self
      administered questionnaire measuring fruit and vegetable intake and personal,
      social and environmental factors during one school lesson. Age-adjusted
      covariance analyses were carried out by gender, for the full sample and for each
      country separately. Proportions responding positively to the constructs are
      presented. RESULTS: Overall, European children held a positive attitude towards
      fruit and vegetable intake. For some constructs, large between-country
      differences were found. Children had a more positive attitude towards fruit than
      towards vegetables, and girls were on average more positive than boys. The
      children perceived their social environment as supportive towards fruit and
      vegetable intake. They reported good to very good availability of fruit and
      vegetables at home. However, availability at school and during leisure time
      activities seemed to be low, both for fruit and for vegetables. CONCLUSION: A
      large majority of the children reported positively to the personal and social
      factors regarding fruit and vegetable intake. As regards availability of fruit
      and vegetables at school and leisure time, and accessibility of fruit and
      vegetables at home, there is room for improvement.

PMID- 16088090
TI  - The pro children intervention: applying the intervention mapping protocol to
      develop a school-based fruit and vegetable promotion programme.
AB  - BACKGROUND/AIMS: The importance of careful theory-based intervention planning is
      recognized for fruit and vegetable promotion. This paper describes the
      application of the Intervention Mapping (IM) protocol to develop the Pro Children
      intervention to promote consumption of fruit and vegetable among 10- to 13-year
      old schoolchildren. METHODS: Based on a needs assessment, promotion of intake of
      fruit and vegetable was split into performance objectives and related personal,
      social and environmental determinants. Crossing the performance objectives with
      related important and changeable determinants resulted in a matrix of learning
      and change objectives for which appropriate educational strategies were
      identified. Theoretically similar but culturally relevant interventions were
      designed, implemented and evaluated in Norway, the Netherlands and Spain during 2
      school years. RESULTS: Programme activities included provision of fruits and
      vegetables in the schools, guided classroom activities, computer-tailored
      feedback and advice for children, and activities to be completed at home with the
      family. Additionally, optional intervention components for community
      reinforcement included incorporation of mass media, school health services or
      grocery stores. School project committees were supported. CONCLUSION: The Pro
      Children intervention was carefully developed based on the IM protocol that
      resulted in a comprehensive school-based fruit and vegetable promotion programme,
      but culturally sensible and locally relevant.

PMID- 16088091
TI  - Beneficial effects of dietary copper supplementation on serum lipids and
      antioxidant defenses in rats.
AB  - BACKGROUND: A nutrition experiment was utilized to investigate the effects of two
      levels of dietary copper (Cu) supplementation on lipid profile and antioxidant
      defenses in serum of rats. METHODS: Male Wistar rats (180-200 g; n = 10) were
      divided into three groups: control group (A), fed a basal diet with 6 microg
      Cu/g, and rats fed a basal diet with Cu (CuSO4) supplementation from aqueous
      solutions, for 4 weeks at the final concentrations of 2 mg Cu/rat (B) and 3 mg
      Cu/rat (C). RESULTS: No significant changes were observed in final body weight,
      body weight gain, food consumption, total serum protein and high-density
      lipoprotein. Cu supplementation reduced the triacylglycerol (TG), total
      cholesterol and low-density lipoprotein (LDL-C). The LDL-C/TG ratio and total
      antioxidant substances (TAS) were higher in (B) and (C) groups than in (A) group.
      There was a positive correlation between Cu supplementation and ceruloplasmin
      levels. The markers of oxidative stress, lipid hydroperoxide and lipoperoxide
      were decreased with Cu supplementation. No alterations were observed in
      superoxide dismutase, indicating saturation of Cu enzyme site. The glutathione
      peroxidase activities (GSH-Px) were increased in both Cu-supplemented groups.
      Considering that a copper-selenium interaction can affect mineral availability of
      both elements, the effects of Cu on TAS and GSH-Px activities were associated
      with increased selenium disposal. CONCLUSIONS: Dietary Cu supplementation had
      beneficial effects on lipid profile by improving endogenous antioxidant defenses
      and decreasing the oxidative stress in vivo.

PMID- 16088092
TI  - Non-alcoholic fatty liver disease in young adult severely obese non-diabetic
      patients in South Italy.
AB  - BACKGROUND/AIMS: In the absence of other causes, obesity increases the risk of
      liver disease. We evaluated the prevalence and degree of metabolic and hepatic
      abnormalities associated with non-alcoholic fatty liver disease (NAFLD) in type
      II-III obesity in a metropolitan area of South Italy. METHODS: 187 (81 M, 106 F)
      young adult non-diabetic obese patients, age range 18-50 years (mean 31.9 +/-
      8.8), body mass index (BMI) > or =30 (mean 47.5 +/- 9.6), consecutively admitted
      from January 2000 to April 2003 to the Obesity Outpatients Clinic entered into
      the study. Patients were divided into two groups: (1) BMI 30.0-39.9, and (2) BMI>
      or =40. Ultrasound detected liver steatosis was classified as: (I) mild; (II)
      moderate, and (III) severe. RESULTS: All patients, except 4, showed a variable
      degree of steatosis: mild was more frequent among females, severe steatosis
      present only in grade III obesity, with higher prevalence in males than in
      females (p < 0.001). Mean serum transaminases, in particular alanine
      aminotransferase (ALT), increased according to BMI and degree of steatosis.
      Homeostasis Model Assessment (HOMA) index, ferritin and fibrinogen levels
      increased with BMI, particularly in severe steatosis. In group 2, patients with
      BMI> or =40 showed a positive correlation between ferritin, aspartate
      aminotransferase (AST) (r = 0.46, p < 0.018), ALT (r = 0.41, p < 0.036) and gamma
      glutamyltransferase (gammaGT) (r = 0.51, p < 0.007), between serum triglycerides
      (TG) and AST (r = 0.28, p < 0.036), ALT (r = 0.30, p < 0.02) and between HOMA and
      ALT (r = 0.30, p < 0.03) and gammaGT (r = 0.35, p < 0.012). In group 2 patients
      with severe steatosis the prevalence of metabolic syndrome according to Adult
      Treatment Panel III (ATP III) was 40%. CONCLUSION: These data suggest that, in
      young adult non-diabetic grade III obese patients, fatty liver is always present
      and strictly related to insulin resistance which, in the presence of severe liver
      steatosis, is also related to serum ferritin.

PMID- 16088093
TI  - Lactational transfer of cadmium from Meriones shawi shawi mothers to their pups
      and its effects on calcium homeostasis and bone calcium in pups.
AB  - Cadmium (Cd) was given to Meriones shawi shawi dams in the diet (1 g CdCl2/1.5 kg
      of diet) from day 1 to day 21 of lactation. Pups were killed at 5, 10, 14 and 21
      days of lactation. Thereafter, liver, kidney, femur and stomach content were
      removed and plasma was collected to element analyses. Cd in stomach content,
      kidney, liver and femur and calcium (Ca) in stomach content, femur and plasma
      were determined in pups by atomic absorption spectrophotometer. The results
      indicate that Cd was transferred to the suckling and it was detected in the
      liver, the kidney and the femur from the 5th, the 10th and the 14th days of age,
      respectively. Stomach content of Ca was increased significantly from the 10th day
      to the end of lactation, whereas Ca levels increase in plasma and femur only at
      day 10 of lactation.

PMID- 16088094
TI  - Effect of ethanol and thermally oxidized sunflower oil ingestion on phospholipid
      fatty acid composition of rat liver: protective role of Cuminum cyminum L.
AB  - AIM: The current study was undertaken to assess the effect of ethanol and
      thermally oxidized sunflower oil ingestion on liver phospholipid fatty acids and
      the protective role of Cuminum cyminum L. METHODS: Ethanol was administered at a
      level of 20% and thermally oxidized sunflower oil at a level of 15% for 45 days.
      C. cyminum was administered at a dosage of 250 mg/kg body weight for 45 days. We
      investigated the changes in the liver phospholipid fatty acid composition.
      RESULTS: Ethanol and thermally oxidized sunflower oil administration modifies the
      fatty acid composition and the analysis of fatty acids showed that there was a
      significant increase in the concentrations of 16:0, 16:1, 18:0, 18:1 and 18:2,
      whereas the concentration of 20:4 was significantly decreased. The concentrations
      of 16:0, 16:1, 18:0, 18:1 and 20:4 were near normal in cumin-treated rats.
      CONCLUSION: The present investigation shows that cumin prevents the changes in
      the composition of fatty acids, which were produced by ethanol and thermally
      oxidized oil.

PMID- 16088096
TI  - The relation between dietary protein, calcium and bone health in women: results
      from the EPIC-Potsdam cohort.
AB  - BACKGROUND/AIMS: The role of dietary protein in bone health is controversial. The
      objective of the present study was to examine the association between protein
      intake, dietary calcium, and bone structure measured by broadband ultrasound
      attenuation (BUA). METHODS: Our analysis includes 8,178 female study participants
      of the European Prospective Investigation into Cancer and Nutrition (EPIC)
      Potsdam Study. Ultrasound bone measurements were performed on the right os
      calcis, and BUA was determined. Dietary intake was assessed by a standardized
      food frequency questionnaire. We applied linear regression models to estimate the
      association between dietary protein and BUA. RESULTS: After multivariate
      adjustment, high intake of animal protein was associated with decreased BUA
      values (beta = -0.03; p = 0.010) whereas high vegetable protein intake was
      related to an increased BUA (beta = 0.11; p = 0.007). The effect of dietary
      animal protein on BUA was modified by calcium intake. CONCLUSION: High
      consumption of protein from animal origin may be unfavourable, whereas a higher
      vegetable protein intake may be beneficial for bone health. Our results
      strengthen the hypothesis that high calcium intake combined with adequate protein
      intake based on a high ratio of vegetable to animal protein may be protective
      against osteoporosis.

PMID- 16088095
TI  - Effects of polyunsaturated/saturated fatty acid ratio and antioxidant
      supplementation on hepatic TBARS and enzyme activities under the maintenance of
      dietary peroxidizability index value in young and adult rats.
AB  - AIMS: To investigate the effects of the polyunsaturated/saturated fatty acid
      (P/S) ratio and antioxidant supplementation on hepatic lipid peroxidation and
      enzyme activities under the control of the dietary peroxidizability index (PI)
      value in young and adult rats. METHODS: We measured thiobarbituric acid-reactive
      substance (TBARS) concentration and enzyme activities in liver tissue. Female
      Sprague-Dawley rats aged 3 and 16 weeks were used. Dietary P/S ratios were 0.38
      and 4.81 (LP and HP) when the PI value was 81.22. The diets were supplemented
      with vitamin E 1,000 mg/kg diet and selenium 2.5 mg/kg diet (LPS and HPS).
      RESULTS: The hepatic TBARS concentration was higher in LP and LPS than in HP and
      HPS. In reducing TBARS concentration, antioxidant supplementation was more
      effective in adult rats than in young rats. Glutathione peroxidase and
      glutathione-S-transferase activities were lower in young rats than in adult rats.
      CONCLUSION: We conclude that dietary fats and antioxidant supplementation play an
      important role in the change of hepatic TBARS concentration when the dietary PI
      value is maintained at the same level. However, with the exception of glutathione
      reductase, no effects of the P/S ratio and antioxidant supplementation on hepatic
      enzyme activities were detected. This may be due to the invisible effects of
      fixed PI value in diets.

PMID- 16088097
TI  - Honey-induced stimulation of blood ethanol elimination and its influence on serum
      triacylglycerol and blood pressure in man.
AB  - The effect of honey on blood alcohol metabolism and the accompanying changes in
      serum triacylglycerol and blood pressure were investigated using volunteers.
      Fifty consenting undergraduates in apparent good health, between the ages of 15
      and 30 years (23.6 +/- 7.4), were recruited for the study. The subjects were
      moderate alcohol drinkers (<30 g ethanol/day), matched in body weight and frame
      size. The participants were given ethanol (0.5 g/kg) and ethanol + honey (0.5
      g/kg + 1.25 ml/kg) on two different occasions separated by 1 week. The results
      show that honey significantly (p < 0.01) increased blood alcohol disappearance
      and elimination rates by 32.4 and 28.6%, respectively, but reduced the
      intoxication time (that is, the time taken to attain zero blood alcohol level)
      and its degree (the peak blood alcohol level) by 30.0 and 4.4%. Ethanol + honey
      further increased serum triacylglycerol and blood pressure by 20.8 and 1.3/1.4%
      when compared with the proportion induced by ethanol after about 10 h of
      ingestion. The occasional use of honey as an anti-intoxicating agent may be
      approved. Meanwhile, further studies on how to ameliorate or prevent the
      associated increase in serum triacylglycerol and blood pressure is required.

PMID- 16088098
TI  - Tissue accretion and milk content of docosahexaenoic acid in female rats after
      supplementation with different docosahexaenoic acid sources.
AB  - BACKGROUND: Docosahexaenoic acid (DHA) is highly concentrated in the mammalian
      nervous and visual system. The fatty acid, which is required by the fetus and the
      newborn, is supplied by the mother from their tissue reservoirs. It has been
      suggested that mother's supplementation with DHA during pregnancy and even before
      pregnancy. Different sources of DHA are available for supplementation such as:
      single-cell algae triglycerides (TG), egg's yolk phospholipids (PL), DHA ethyl
      esther (EE), and sn-2 DHA monoacylglyceride (MG). We evaluated comparatively the
      effectiveness of these different DHA sources to produce tissue DHA accretion and
      to increase milk DHA content. METHODS: Female Wistar rats fed a diet which
      provided no DHA, were daily supplemented by 40 days before mating (BM) and during
      the pregnancy with either TG, PL, EE, or MG to an amount which provided 8 mg/kg
      b.w. of DHA. Samples of blood plasma, erythrocytes, hepatic and adipose tissue
      were obtained from rats at the BM condition and after the delivery (AD), and milk
      samples were also obtained from the gastric content of the pups nursed by the
      rats at day 3, 11 and 20 of suckling. Samples were processed to assess DHA and
      arachidonic acid (AA) content by gas-chromatography. RESULTS: TG, PL, EE, and MG
      supplementation produced a similar intestinal absorption of DHA as estimated from
      the plasma DHA at the BM condition. However, PL and MG supplementation produced a
      higher accretion of DHA into erythrocytes, hepatic, and adipose tissue than TG
      and EE supplementation at the BM condition. AA content was not modified by the
      different supplementing oils. A reduction of the DHA content of plasma,
      erythrocytes, hepatic and adipose tissue at the AD condition was observed, and a
      reduction of AA for the hepatic and adipose tissues was also observed, suggesting
      the importance of these tissues as DHA and AA reservoirs. Milk secretion from PL
      and MG supplemented rats showed a higher DHA content than secretion from TG- and
      EE-supplemented rats. CONCLUSIONS: We conclude that PL and MG supplementation
      provides higher tissue DHA accretion and higher milk DHA content than TG and EE
      supplementation. However, we were not able to visualize the comparative
      advantages derived from PL vs. MG supplementation.

PMID- 16088099
TI  - Ultrastructural study of normal and degenerating nerve fibers in the
      protocerebral tract of the crab Ucides cordatus.
AB  - Wallerian degeneration is a very well described phenomenon in the vertebrate
      nervous system. In arthropods, and especially in crustaceans, nerve fiber
      degeneration has not been described extensively. In addition, literature shows
      that the events do not follow the same patterns as in vertebrates. In this study
      we report, by qualitative and quantitative ultrastructural analyses, the features
      and time course of the protocerebral tract degeneration following extirpation of
      the optic stalk. No remarkable changes were observed seven days after lesion.
      After 28 days the protocerebral tracts presented apparently preserved small and
      large diameter axons and some degenerating medium axons, with irregular contours
      and empty-looking aspect of the axoplasm. Forty days after the ablation of the
      optic stalks, both small (type I) and medium (type II and III) axons revealed
      signs of partial or total degeneration, but large nerve fibers (type IV) were
      still intact. After 45 days, the tract showed signs of advanced stage of
      degeneration and, apart from large axons, normal-looking fibers were almost
      absent. At these 3 last time points, degenerating axons displayed different
      electron densities and aspects, probably correlating to different onset times of
      the process. In addition, cells with granules in their cytoplasm, possibly
      hemocytes, were quite distinct, especially at 40 and 45 days after axotomy. These
      cells might share with glial cells the function of phagocytosis of cellular
      debris during the protocerebral tract degeneration. Quantitative analysis showed
      that the number of degenerating fibers increased significantly from 28 to 40 days
      after lesion, whereas the number of normal fibers decreased accordingly.
      Measurements of cross-sectional areas of normal and degenerating axons showed
      that types II and III (medium) start to degenerate before type I (small). Type IV
      (large) axons do not degenerate, even after 40 days. Therefore, we can conclude
      that degeneration in these afferent fibers starts late after axotomy, but
      proceeds at a faster rate afterwards until the complete degeneration of small and
      medium axons.

PMID- 16088100
TI  - Mental rotation and rotational invariance in the Rhesus monkey (Macaca mulatta).
AB  - The mode of visual information processing during visuospatial tasks differs
      across species and is supposed to depend on evolutionary and ecological factors.
      Humans show reaction times that increase with angular disparity when tested in
      mental rotation tasks. Pigeons show a time-independent rotational invariance that
      possibly evolved in response to the horizontal reference plane birds perceive
      while flying. As it was suggested that hominids may have secondarily lost the
      ability of rotational invariance while retreating from arboreal living and
      evolving upright gait where the vertical reference plane is more important,
      mental rotation tests with various recent primate species promise to model the
      evolution of the respective modes of information processing. The results of
      recent corresponding experiments with a mainly arboreal living primate species
      could not be explained by either mode, thus supporting the idea of information
      processing systems having gradually evolved. Here, we conducted mental rotation
      experiments with three Rhesus monkeys, a more terrestrial living primate species.
      In a two-alternative matching-to-sample procedure, we measured the monkeys'
      reaction times for decisions between rotated figures representing image and
      mirror-image of a previously shown upright sample. The results of our three
      monkeys were inconsistent. Linear regression analyses showed for one test animal
      significant correlation coefficients for mean reaction times depending on angular
      disparity and thus clearly indicated mental rotation. The other two test animals
      showed reaction times not consistent with mental rotation, whereas rotational
      invariance might explain the responses to the smaller angles of rotation. Our
      results suggest that two separately evolved information processing systems may be
      coexisting to a certain extent in species with correspondingly overlapping
      ecological demands.

PMID- 16088101
TI  - Sonic motor pathways in piranhas with a reassessment of phylogenetic patterns of
      sonic mechanisms among teleosts.
AB  - Sound production has evolved independently a number of times among teleost
      fishes. In most cases, sound is generated by fast contracting muscles that
      vibrate the swim bladder by way of their direct attachment (intrinsic muscles) or
      indirectly by way of other skeletal elements (extrinsic muscles). This study
      focuses on the red and black piranha, Pygocentrus nattereri and Serrasalmus
      rhombeus (superorder Ostariophysi, Order Characiformes), that have extrinsic swim
      bladder sonic muscles innervated by the third and fourth spinal nerves. This
      innervation pattern diverges from that found in most teleosts, including the
      closely related catfishes (Ostariophysi, Siluriformes), where sonic muscles are
      innervated by ventral occipital nerve roots that arise just caudal to the vagus
      nerve. Here, we tested the hypothesis that piranhas would also differ from most
      other teleosts in the location of their sonic motor neurons. Following biotin
      labeling of branches of the third and fourth spinal nerves that innervate the
      sonic muscles in the red and black piranha, sonic motor neurons were identified
      amongst other non-sonic motor neurons in the central part of the spinal cord,
      slightly ventrolateral to the central canal. To our knowledge, this is the first
      example of sonic motor neurons positioned entirely within the spinal cord. In the
      other species so far studied, sonic motor neurons form well-defined nuclei that
      extend from far caudal levels of the medulla into the rostral spinal cord and are
      located either within the ventral motor column or near the midline, close to or
      just ventrolateral to the fourth ventricle and central canal. A piranha-like
      pattern may be more widespread among characiforms and is likely present in other
      teleost orders, e.g., Sciaenidae (drumfishes), that also have sonic muscles
      innervated by spinal nerves.

PMID- 16088102
TI  - Prey tracking by larval zebrafish: axial kinematics and visual control.
AB  - High-speed imaging was used to record the prey-tracking behavior of larval
      zebrafish as they fed upon paramecium. Prey tracking is comprised of a variable
      set of discrete locomotor movements that together align the larva with the
      paramecium and bring it into close proximity, usually within one body length.
      These tracking behaviors are followed by a brief capture swim bout that was
      previously described [Borla et al., 2002]. Tracking movements were classified as
      either swimming or turning bouts. The swimming bouts were similar to a previously
      characterized larval slow swim [Budick and O'Malley, 2000], but the turning
      movements consisted of unique J-shaped bends which appear to minimize forward
      hydrodynamic disturbance when approaching the paramecium. Such J-turn tracking
      bouts consisted of multiple unilateral contractions to one side of the body. J
      turns slowly and moderately alter the orientation of the larva - this is in
      contrast to previously described escape and routine turns. Tracking behaviors
      appear to be entirely visually guided. Infra-red (IR) imaging of locomotor
      behaviors in a dark environment revealed a complete absence of tracking
      behaviors, even though the normal repertoire of other locomotive behaviors was
      recorded. Concomitantly, such larvae were greatly impaired in consuming
      paramecia. The tracking behavior is of interest because it indicates the presence
      of sophisticated locomotor control circuitry in this relatively simple model
      organism. Such locomotor strategies may be conserved and elaborated upon by other
      larval and adult fishes.

PMID- 16088103
TI  - Role of the dialyzer membrane on the overall phosphate kinetics during
      hemodialysis.
AB  - BACKGROUND/AIM: We investigated the potential role of the membrane type on
      phosphate kinetics. METHODS: Six patients on dialysis (HD) were studied using
      modified cellulose (Hemophan), ethylene-vinyl alcohol (EVAL) and
      polyacrylonitrile (PAN). Total (TPR), extracellular (EPR) and intracellular (IPR)
      phosphate removal and effective dialyzer phosphate clearance (K(d)) were
      determined by the DDQ method. The intercompartment transfer coefficient (K(C))
      was calculated using a mathematical model. Erythrocyte phosphate (P(ERY)) and 2,3
      biphosphoglycerate (2,3-BPG) concentrations were determined before and after HD.
      RESULTS: TPR was 1.2+/-0.4, 1.10+/-0.4 and 1.09+/-0.4 g with Hemophan, EVAL and
      PAN, respectively (p=n.s.). EPR and IPR were independent of membrane type. There
      was no difference in K(C) between membranes (321+/-70, 338+/-92 and 341+/-83
      ml/min, respectively). The P(ERY) and 2,3--BPG remained statistically
      insignificant for all membranes. CONCLUSION: Our results show that the type of
      membrane does not influence the kinetics of phosphate during dialysis, neither in
      the transfer from plasma to dialysate nor from the intra- to the extracellular
      compartment.

PMID- 16088104
TI  - Does bicarbonate transfer have relevant hemodynamic consequences in standard
      hemodialysis?
AB  - BACKGROUND: In a previous study we demonstrated that mild metabolic alkalosis
      resulting from standard bicarbonate hemodialysis induces hypotension. This study
      aimed to compare hemodynamic consequences of either a decrease in the dialysate
      bicarbonate from 32 to 26 mmol/l or an increase in the dialysate calcium of 0.25
      mmol/l and to verify whether the calcium shift secondary to alkalemia explains
      the consequences on blood pressure. METHODS: In this randomized controlled trial
      with a single-blind, cross-over design, we used dialysis liquids with two
      different bicarbonate (32 mmol/l in modalities A and C, and 26 mmol/l in modality
      B) and calcium (1.25 mmol/l in modalities A and B, and 1.50 mmol/l in modality C)
      concentrations, and in 27 patients, 243 dialysis sessions, compared blood
      pressure, heart rate and the incidence of hypotension. RESULTS: No significant
      differences were seen between A and B while an increase in systolic and diastolic
      blood pressures and a decrease in the incidence of hypotension (10.5 vs. 1.2%, p
      < 0.05) were documented in C. The subgroup of patients who with A showed a lower
      mean systolic blood pressure received more angiotensin-converting enzyme
      inhibitors or angiotensin II type-1 receptor blockers (36 vs. 0%, p<0.05) and in
      C showed a less important increase in systolic and diastolic pressures, but the
      incidence of hypotensive episodes between A and B was not significantly different
      (9.1 vs. 15.1%). CONCLUSIONS: In the present study it was not possible to
      demonstrate hemo dynamic instability associated with mild metabolic alkalosis.
      Even in the subgroup showing a lower blood pressure with a higher dialysate
      bicarbonate, significant hemodynamic or clinical consequences were not noticed.
      The calcium shift (0.05 mmol/l) related to alkalemia would justify a mean
      decrease in systolic blood pressure of only about 1 mm Hg.

PMID- 16088105
TI  - Volume status and blood pressure in continuous ambulatory peritoneal dialysis
      patients.
AB  - The pathophysiology of hypertension in dialysis patients is largely attributed to
      positive sodium balance and volume expansion. Whereas the relationship between
      fluid status and blood pressure control in hemodialysis patients is well
      established, this relationship is not well studied in peritoneal dialysis
      patients. METHODS: 100 stable CAPD patients who had been dialyzed for more than 3
      months, as well as 60 healthy controls, were studied cross-sectionally. CAPD
      patients were divided into three groups according to their blood pressure level:
      group 1 (normotension), group 2 (controlled hypertension with antihypertensive
      medication (AHM)) and group 3 (uncontrolled hypertension with AHM). Extracellular
      water (ECW) and intracellular water (ICW) were measured using bioimpedance
      spectroscopy in all subjects. Dialysis adequacy and transport test was conducted
      in each patient. RESULTS: Height normalized ICW (nICW) was much lower, and
      ECW/ICW was higher in both male and female dialysis patients as compared to
      healthy controls. nECW was also significantly higher in group 3 when compared to
      group 1. The dose of AHM was similar in group 2 and group 3. In female CAPD
      patients, there were no differences in urinary volume (UV) and the total fluid
      removal among the three patient groups. However, in male CAPD patients, UV and
      total fluid removal were significantly higher in group 3 than in group 1. Renal
      and total removal of sodium was also significantly higher in group 3 male
      patients than group 1. CONCLUSIONS: Peritoneal dialysis patients with
      uncontrolled hypertension are more volume overloaded and their blood pressure may
      be difficult to control by AHM alone. These findings indicate that volume control
      preferably by dietary salt and fluid restriction should be intensified in
      hypertensive CAPD patients.

PMID- 16088106
TI  - Effect of oral sodium bicarbonate supplementation on interdialytic weight gain,
      plasma sodium concentrations and predialysis blood pressure in hemodialysis
      patients.
AB  - BACKGROUND: Correction of metabolic acidosis in dialysis patients should be
      considered of paramount importance. However, consuming sodium bicarbonate tablets
      during the interdialytic interval to reach predialysis bicarbonate levels of 23-
      24 mmol/l is not widespread due to the fear of greater interdialytic weight gain
      and fluid overload. For this reason we investigated in a cross-sectional and in
      an interventional study the effect of oral sodium bicarbonate supplementation on
      body weight gain, plasma sodium concentrations and predialysis blood pressure in
      a group of stable uremic patients on regular hemodialysis (HD) treatment. STUDY
      DESIGN: 110 patients (67 men, 43 women), mean age 67+/-15 (range 22--89) years,
      on regular chronic HD treatment for 6--372 (median 48) months were studied. 70
      patients were on regular oral bicarbonate supplementation for at least 4 weeks
      (group A), 40 patients were not on oral bicarbonate supplementation (group B).
      The following parameters were recorded: dry body weight (DBW), interdialytic
      weight gain (IWG), body mass index (BMI), plasma sodium (Na), serum pH, serum
      bicarbonate (sBic), K(t)/V, normalized protein catabolic rate (PCRn), predialysis
      systolic (SBP) and diastolic (DBP) blood pressure, and bicarbonate therapy
      (g/day). 18 patients not on oral bicarbonate supplementation with sBic
      levels</=20 mmol/l were started on oral bicarbonate therapy and were
      prospectively followed in the context of an interventional study of correction of
      chronic metabolic acidosis. The same parameters were recorded before (pre) and
      after (post) 4 months of oral bicarbonate supplementation. RESULTS: Serum pH and
      sBic concentrations were significantly higher in patients in group A compared to
      patients in group B (pH 7.37 +/- 0.02 group A vs. 7.33+/- 0.02 group B: p<0.001:
      sBic 23.8+/-1.4 group A vs. 20.9+/-1.4 group B: p<0.0001). Age, DBW, BMI, IWG,
      SBP, DBP, Na, K(t)/V and PCRn did not differ between groups. The mean daily dose
      of oral sodium bicarbonate administered to patients in group A was 1.9+/-0.9
      (range 1--5, median 2) g/day. Also in the 18 patients who started bicarbonate
      treatment, a significant increase in serum pH and sBic concentrations and a
      significant reduction in PCRn were observed. No significant change in DBW, IWG,
      SBP, DBP and Na concentrations after 4 months of treatment was found.
      CONCLUSIONS: Our data show that in stable uremic patients on regular HD
      treatment, oral daily administration of sodium bicarbonate is effective in
      correcting mild-moderate chronic metabolic acidosis, and does not cause increased
      interdialytic body weight gain, different plasma sodium concentrations and
      different systolic-diastolic blood pressure levels compared to patients not on
      oral sodium bicarbonate supplementation.

PMID- 16088107
TI  - Interleukin-1 gene cluster polymorphisms are associated with nutritional status
      and inflammation in patients with end-stage renal disease.
AB  - BACKGROUND: Wasting and inflammation are two common risk factors for death in
      patients with end-stage renal disease (ESRD). Interleukin-1beta (IL-1beta) and
      its receptor antagonist (IL-1Ra) may play a pivotal role in the pathogenesis of
      wasting and inflammation. METHODS: To investigate effects of the IL-1 gene
      cluster polymorphisms on wasting and inflammation, we studied 189 ESRD patients
      (52+/- 12 years, 62% males) close to the start of renal replacement therapy. 205
      healthy volunteers served as controls. We analyzed the IL-1B -511C/T, -31C/T, and
      +3954C/T polymorphisms as well as a variable number of a tandem repeat (VNTR) in
      IL-1RN. Nutritional parameters included serum albumin level, subjective global
      nutritional assessment (SGA), and body composition evaluated by dual-energy X-ray
      absorptiometry (DXA). We used serum high-sensitivity C-reactive protein (hsCRP)
      as a marker of inflammation. RESULTS: Wasting (SGA>1) was present in 31%, whereas
      inflammation (CRP>/=10 mg/l) was present in 36% of the patients. The male
      carriers of the -511T/T and -31C/C genotypes had a lower prevalence of wasting
      (p<0.05), higher body mass index (BMI) (p<0.05), and higher lean body mass (LBM)
      (p<0.01). In a stepwise multiple regression model, age (p<0.05), BMI (p<0.01) and
      the IL-1B -511 genotype (p<0.01) were independently associated with LBM. The
      carriers of the +3954T allele had a lower prevalence of inflammation (p<0.05) and
      lower serum hsCRP (p<0.05). The VNTR in IL-1RN was not associated with any
      markers. CONCLUSION: The investigated IL-1 gene cluster polymorphisms were
      associated with nutritional status and inflammation in ESRD patients, but marked
      differences were found between the genders. These polymorphisms could have
      prognostic utility for predicting wasting and inflammation in ESRD patients.

PMID- 16088108
TI  - Matrix metalloproteinases in cerebrovascular diseases.
AB  - Matrix metalloproteinases are important factors for tissue remodelling and are
      activated during several physiological and pathological conditions, including
      cerebrovascular diseases. We give an overview of the structure, production and
      physiological effects of these widely distributed proteases and describe the
      genetic background and regulation pathways. In particular, we discuss the role of
      matrix metalloproteinases in vascular remodelling concerning ischaemic stroke,
      brain haemorrhage, vascular dementia, carotid artery plaques and cerebral
      aneurysms.

PMID- 16088109
TI  - Johann Jacob Wepfer award 2005 of the ESC to Dr. Jean-Claude Baron.

PMID- 16088110
TI  - Stroke research in the modern era: images versus dogmas.
AB  - Recovery of function following ischaemic stroke is a fascinating clinical
      observation. It comprises several modes, e.g. spectacular recovery in a matter of
      hours or days and gradual recovery over months or even years. That a non
      functioning neural system can regain its function, even partially so, is
      challenging because of the obvious therapeutic implications. Until the mid-70s,
      however, dogmas largely prevailed which underpinned the then nihilistic approach
      to stroke patients. Proving these dogmas wrong has been a major achievement of
      modern stroke research. Thanks particularly to physiological imaging, key
      observations from the basic neurosciences have translated into the clinical realm
      in ways immediately understandable to the clinician, allowing the emergence of
      pathophysiology-based management.

PMID- 16088111
TI  - History of blood transfusion before 1990 is a risk factor for stroke and
      cardiovascular diseases: the Japan collaborative cohort study (JACC study).
AB  - BACKGROUND: We have previously shown novel evidence that history of blood
      transfusion is a risk factor for mortality from subarachnoid hemorrhage. This
      study was conducted to assess history of transfusion as a risk factor for other
      hemorrhagic stroke or ischemic stroke and cardiovascular diseases. STUDY DESIGN
      AND METHODS: A total of 88,312 Japanese participants (36,823 men and 51,489
      women), aged 40-79 years, without history of stroke, heart disease or cancer,
      completed a questionnaire including history of transfusion under the JACC Study
      from 1988 to 1990. Participants were followed up annually until deceased, or when
      they moved away from the surveyed community, or at the end of 1999. The
      underlying causes of death were determined according to the International
      Classification of Diseases, 10th revision (ICD-10). RESULTS: Total follow-up
      person-years were 871,437 (males 359,437, females 512,000). During this 10-year
      period, 309 died from intracerebral hemorrhage, 587 from ischemic stroke and 472
      from coronary heart disease. The multivariate relative risks of a transfusion
      history were 2.16 (95% CI 1.42-3.27, p < 0.001) for intracerebral hemorrhage,
      1.63 (95% CI 1.18-2.27, p = 0.004) for ischemic stroke and 1.66 (95% CI 1.17
      2.36, p = 0.005) for coronary heart disease, after adjustment for conventional
      cardiovascular risk factors. CONCLUSION: A transfusion history was associated
      with increased mortality from stroke and coronary heart disease.

PMID- 16088112
TI  - Association of the fibrinolytic system and hemorheology with symptoms in patients
      with carotid occlusive disease.
AB  - BACKGROUND AND OBJECTIVES: The risk of stroke caused by a symptomatic high-grade
      carotid stenosis (CS) is high. Disturbed balance between the procoagulant and
      fibrinolytic activity in blood associated with unfavorable hemorheology could
      render CS symptomatic. We wanted to assess whether hemostatic and fibrinolytic
      plasma markers as well as basic indicators of hemorheology differentiate
      asymptomatic and symptomatic patients with a high-grade CS and whether they are
      associated with the macroscopic appearance of the plaque and the rate of
      microembolization. METHODS: We recruited 92 consecutive consenting patients
      referred to the neurological or the surgical department of our university
      teaching hospital for treatment of their high-grade CS. Blood samples were
      collected before surgery for determination of prothrombin fragments F1 and 2,
      thrombin-antithrombin complex, tissue-type plasminogen activator (tPA) activity
      and antigen, plasminogen activator inhibitor-1 (PAI-1) activity and antigen, D
      dimer, homocysteine, fibrinogen, in plasma, and hematocrit in blood, and the
      patients underwent transcranial Doppler ultrasonology for evaluation of
      microembolic signals (MES). RESULTS: Patients with symptomatic plaques had higher
      hematocrit levels (p = 0.04), as well as trends for higher tPA antigen and MES
      rate (p = 0.07). Hematocrit, tPA antigen, and PAI-1 antigen and activity were
      positively correlated with the degree of stenosis. Ulceration was more common in
      symptomatic plaques but did not reflect variables of hemostasis or fibrinolysis.
      In multivariate analysis, tPA antigen and hematocrit were risk factors for a
      symptomatic high-grade stenosis. CONCLUSION: Mediators of fibrinolysis and
      unfavorable hemorheology may contribute to the development of a symptomatic
      disease in patients with a high-grade CS.

PMID- 16088113
TI  - A systematic comparison of the quality and volume of published data available on
      novel risk factors for stroke versus coronary heart disease.
AB  - BACKGROUND: To identify new treatments to prevent stroke, it is important that we
      have reliable data on potential novel risk factors. METHODS: We studied seven
      novel vascular risk factors [apo-lipoprotein (b), C-reactive protein, Chlamydia
      pneumoniae, fibrin-D dimer, fibrinogen, Helicobacter pylori and lipoprotein (a)]
      and compared the amount of published data on their relations with ischaemic
      stroke versus acute coronary events by systematic review of all studies published
      up to 2003. RESULTS: From a total of 22,875 abstracts reviewed, 266 eligible
      studies were identified (167 case-control studies and 99 cohort studies). Two
      hundred and eleven (79%) studies included coronary events as an outcome for the
      purpose of a risk factor analysis. In 186 (70%) studies, coronary events were the
      only outcome that was analysed. Only 73 (27%) studies included stroke or TIA as
      an outcome event, and only 45 studies (17%) reported risk factor analyses for
      ischaemic stroke separately. These results were qualitatively consistent across
      the risk factors studied and the relative lack of data on risk factors for stroke
      was even greater in prospective cohort studies. CONCLUSION: Data on novel risk
      factors for stroke are lacking compared with the equivalent data for acute
      coronary events, and there are very few data on specific subtypes of ischaemic
      stroke.

PMID- 16088114
TI  - Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures
      in women after stroke: a randomized controlled trial.
AB  - OBJECTIVE: Vitamin D supplementation is suggested to reduce the risk of falls
      among ambulatory or institutionalized elderly subjects. The present study was
      undertaken to address the reduced risk of falls and hip fractures in patients
      with long-standing stroke by vitamin D supplementation. METHODS: Ninety-six
      elderly women with poststroke hemiplegia were followed for two years. Patients
      were randomly assigned to one of the two groups, and 48 patients received 1,000
      IU ergocalciferol daily, and the remaining 48 received placebo. The number of
      falls per person and incidence of hip fractures were compared between the two
      groups. Strength and tissue ATPase of skeletal muscles on the nonparetic side
      were assessed before and after the study. RESULTS: At baseline, serum 25
      hydroxyvitamin D levels were in the deficient range (<10 ng/ml) in all patients;
      and vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25
      dihydroxyvitamin D levels. Vitamin D treatment accounted for a 59% reduction in
      falls (95% CI, 28-81%; p = 0.003). There were increases in the relative number
      and size of type II muscle fibers and improved muscle strength in the vitamin D
      treated group. Hip fractures occurred in 4 of 48 placebo group and 0 in 48
      vitamin D2 group during the 2-year study period (log-rank, p = 0.049).
      CONCLUSION: Vitamin D may increase muscle strength by improving atrophy of type
      II muscle fibers, which may lead to decreased falls and hip fractures.

PMID- 16088115
TI  - Cost-effectiveness analysis of thrombolytic treatment for stroke.
AB  - PURPOSE: Thrombolysis is used to treat stroke patients based on the National
      Institute of Neurological Disorders and Stroke study and meta-analysis results.
      We present a cost-effectiveness analysis based on a probabilistic model of the
      use of thrombolytic therapy in stroke treatment. METHODS: We surveyed patients
      who had had a stroke during their hospital stay and examined them again 1 year
      after release from the hospital to obtain data on costs and natural history. We
      then calculated utility weights using the European Quality of Life Questionnaire.
      When the model runs, 4,000 Monte Carlo simulations are undertaken in which each
      parameter value changes depending on its probability distribution. The results
      are expressed in terms of the cost-effectiveness plane and the cost-effectiveness
      acceptability curve. RESULTS: We studied 435 patients, of whom 304 had had an
      ischemic stroke. One year later, 216 were still alive. The mean utility values
      were 0.22 for disabled patients and 0.77 for autonomous patients. The incremental
      cost-effectiveness ratio (ICER) obtained by means of the parameters was -19,000
      EUR/quality-adjusted life year, reflecting a saving of 6,000 EUR and a health
      benefit for patients. The cost-effectiveness plane showed that thrombolysis was a
      dominant variable in 96.1% of simulations. In the acceptability curves, only 0.4
      of simulations obtained an ICER higher than the societal threshold. CONCLUSIONS:
      Thrombolytic therapy seems to be a useful intervention because it is inexpensive
      and cost-effective. The key factor is the decreased rate of disability, which
      results in a better quality of life of the patient and lower costs.

PMID- 16088116
TI  - Hypertension after acute stroke and clinical outcome.

PMID- 16088117
TI  - Delayed intracranial vasospasm following carotid endarterectomy.

PMID- 16088118
TI  - Acute intracranial hypertension due to occlusion of the brachiocephalic vein in a
      patient undergoing hemodialysis.

PMID- 16088119
TI  - Hemilingual spasm associated with tortuosity of the extracranial internal carotid
      artery.

PMID- 16088120
TI  - Effectiveness of antiinfectives.
AB  - BACKGROUND: Helicobacter pylori is one of the most common infections of mankind,
      with persistent colonization causing significant morbidity and mortality.
      TREATMENT: First-line therapy, consisting of 7-day treatment with a proton pump
      inhibitor or ranitidine bismuth citrate, amoxicillin and clarithromycin, with
      second-line therapy, consisting of a proton pump inhibitor, bismuth,
      metronidazole, and tetracycline, in the case of failure, is chosen as the most
      cost-effective method of H. pylori eradication. CONCLUSION: The effectiveness of
      these antiinfectives is limited by lack of compliance with treatment regimens,
      and increasing antibiotic resistance.

PMID- 16088121
TI  - Activity of cladribine combined with etoposide in heavily pretreated patients
      with indolent lymphoid malignancies.
AB  - We determined the effectiveness and toxicity of combined chemotherapy consisting
      of etoposide 100 mg/m(2)/day i.v. and cladribine (2-CdA) 0.12 mg/kg/day i.v. each
      for 5 days (EC regimen) in the treatment of refractory or relapsed low-grade non
      Hodgkin's lymphoma and chronic lymphocytic leukemia. The cycles were repeated
      every 28 days, reaching a maximum of six courses. Twenty patients entered the
      study. All patients had received three or more cycles of chemotherapy before the
      EC regimen (median 8, range 3-19). Thirteen patients received 2-CdA before the EC
      regimen. Seven out of 20 patients (35%) responded, including one complete
      response. Median overall survival time of responding patients was 22 months
      (range 3-30). Myelosuppression and infections were the major toxicity of the EC
      regimen.

PMID- 16088122
TI  - Exposure to therapeutic concentrations of ritonavir, but not saquinavir, reduces
      secreted aspartyl proteinase of Candida parapsilosis.
AB  - The effect of ritonavir and saquinavir, HIV proteinase inhibitors, on the
      secreted aspartyl proteinase (Sap) activity of Candida parapsilosis was studied.
      In a proteinase-inducing medium (yeast carbon base-bovine serum albumin), Sap
      activity in all clinical isolates of C. parapsilosis (n = 20) was observed at 37
      degrees C but not at 22 degrees C. The presence of ritonavir at a concentration
      of 8 microg/ml produced an inhibition close to 50% albumin consumption and also
      delayed yeast growth; however, saquinavir did not have any effect on growth or on
      Sap activity. In Sabouraud broth, which does not induce Sap production, no effect
      was shown on yeast growth by either of the two HIV proteinase inhibitors studied.

PMID- 16088123
TI  - Evidence for active drug efflux in fluoroquinolone resistance in Clostridium
      hathewayi.
AB  - BACKGROUND: Most fluoroquinolones have shown limited effectiveness against
      anaerobic bacteria. Evidence for a multidrug efflux pump, like those involved in
      fluoroquinolone resistance in some other bacteria, was investigated in
      Clostridium hathewayi. METHODS: A parent strain of C.hathewayi was isolated from
      human intestinal microflora on a medium with a low concentration of norfloxacin
      and a mutant strain was selected from it on a medium with a high concentration of
      norfloxacin. Fluoroquinolone sensitivity, drug accumulation, and the effects of
      different concentrations of fluoroquinolones on the kinetics of growth in the
      presence and absence of efflux pump inhibitors were measured. RESULTS: Both
      strains were resistant to several fluoroquinolones and dyes. The pump inhibitor
      reserpine increased the sensitivity of both strains to some drugs; it affected
      the growth kinetics and the efflux of norfloxacin and ethidium bromide.
      CONCLUSION: The efflux of fluoroquinolone appears to be one reason for
      fluoroquinolone resistance inC. hathewayi.

PMID- 16088124
TI  - Activity of ceftibuten, cefaclor, azithromycin, clarithromycin, erythromycin and
      telithromycin against Streptococcus pyogenes clinical isolates with different
      genotypes and phenotypes.
AB  - BACKGROUND: The growing number of macrolide-resistant strains of Streptococcus
      pyogenes represents an increasing worldwide problem. Macrolide resistance in S.
      pyogenes is mediated by several different genes, which determine different levels
      of resistance to macrolides, lincosamides and streptogramin B (MLS). METHODS:
      This study compared the in vitro antimicrobial activity of azithromycin,
      clarithromycin, erythromycin, ceftibuten, cefaclor, and telithromycin against 287
      strains of S. pyogenes by the broth microdilution method. All strains were
      characterized both phenotypically and genotypically for erythromycin resistance
      and most of them have been M-typed by means of PCR. RESULTS: Ceftibuten and
      cefaclor showed the best antimicrobial activity, while MIC values for
      telithromycin were higher against constitutively MLS (cMLS)-resistant strains
      rather than against the other phenotypes. CONCLUSION: Oral cephalosporins retain
      the best activity against S. pyogenes; showing good activity except for cMLS
      resistant strains, telithromycin is a valid alternative to these antimicrobials.

PMID- 16088125
TI  - Induction of apoptosis by the adenosine derivative IB-MECA in parental or
      multidrug-resistant HL-60 leukemia cells: possible relationship to the effects on
      inhibitor of apoptosis protein levels.
AB  - BACKGROUND: The effects of the A(3) adenosine receptor (A(3)AR) agonist IB-MECA
      were examined in HL-60 leukemia and in its multidrug-resistant variant HL-60R
      cells. METHODS: Cytotoxicity was evaluated by MTS assays and apoptosis by flow
      cytometry analyses of DNA fragmentation and phosphatidylserine exposure. The
      mRNAs of A(3)AR and inhibitor of apoptosis proteins (IAPs) were determined by RT
      PCR. RESULTS: A(3)AR expression was similar in HL-60 and HL-60R cells. At > or
      =100 microM, IB-MECA exhibited strong cytotoxic and apoptotic effects in HL-60,
      but not in HL-60R cells. This activity was not modified by the A(3)AR antagonist
      VUF5574, the P-glycoprotein inhibitor verapamil, the adenosine uptake inhibitor
      NBTI or the anti-Fas antibody ZB4. HL-60R cells showed higher levels of different
      IAPs than HL-60 cells. IB-MECA 100 microM downregulated HIAP1, NAIP and survivin
      mRNAs in HL-60, but not in HL-60R cells. CONCLUSIONS: The antitumor effects of IB
      MECA are not mediated by A(3)AR in HL-60 cells, where the proapoptotic mechanism
      of the compound may involve downregulation of IAPs. The resistance of HL-60R
      cells to IB-MECA may depend on their elevated levels of IAPs.

PMID- 16088127
TI  - Cor triatriatum sinister in a 61-year-old patient.

PMID- 16088126
TI  - Effect of antibiotic treatment on bacterial attachment to a DePuy Enduron
      orthopedic implant.
AB  - BACKGROUND: The increasing incidence of bacterial infections in orthopedic
      surgery might be related to the increasing application of artificial devices. In
      most cases, bacteria multiply on the surface of implants in biofilms. Poor
      penetration of antibiotics, frequent necessity of prosthesis removal, chronic
      processes and financial costs emphasize the significance of preventive measures.
      METHOD: Adhesion of bacterial strains (two Staphylococcus aureus, two coagulase
      negative staphylococci and two Pseudomonas aeruginosa strains isolated from
      orthopedic patients' wounds) to the surface of a polyethylene cup was
      investigated using an ultrasonic method. Results were compared to the adhesive
      ability of three Hungarian standard strains. The effect of antibiotic treatment
      (cefuroxime, cefotaxime, amoxicillin with clavulanic acid and amikacin) has been
      examined. RESULTS: The staphylococcal strains showed significantly higher
      adhesive ability than Pseudomonas strains. Antibiotic treatment significantly
      reduced the attachment of bacteria. The higher the concentration of the
      antibiotics, the higher was the decrease in bacterial adhesion. CONCLUSIONS:
      Antibiotic prophylaxis was proven to be effective against bacterial adhesion,
      and, if applied at the proper time at the highest tolerable dose, it might
      prevent the formation of biofilms.

PMID- 16088128
TI  - Effects of angiotensin-converting enzyme polymorphism on aortic elastic
      parameters in athletes.
AB  - BACKGROUND: Physiologic adaptations in an athlete's heart include increased left
      and right ventricular chamber size, left ventricular wall thickness and mass.
      Angiotensin-converting enzyme (ACE) is a key enzyme in angiotensin II production
      causing cardiac hypertrophy. The cloning of the ACE gene has made it possible to
      identify a deletion (D)-insertion (I) polymorphism that appears to affect the
      level of serum ACE activity. Therefore, the ACE genes, which have been shown to
      be polymorphic, could be candidate genes for large-artery stiffness. METHODS: 56
      endurance athletes and 46 sedentary subjects were included in this study, and
      they underwent both complete echocardiographic examination, and analysis of ACE
      insertion (I) and deletion (D) allele frequencies in peripheral blood. The aortic
      diameter was recorded by M-mode echocardiography at a level 3 cm above the aortic
      valve. Aortic systolic diameter was measured at the time of full opening of the
      aortic valve, and diastolic diameter was measured at the peak of QRS. Aortic
      strain, stiffness index and distensibility were calculated. RESULTS: Left
      ventricular mass index and left ventricular ejection fraction were significantly
      higher in athletes than controls (p < 0.001). The aortic distensibility index and
      strain were significantly greater in athletes compared with controls
      (respectively: 5.8 +/- 2.7 vs. 4.7 +/- 1.8 cm(-2) dyn(-1) 10(-6), p = 0.017; 12.3
      +/- 2.4 vs. 9.3 +/- 3.1, p < 0.001). The aortic stiffness index was significantly
      lower in athletes than in controls (4.8 +/- 1.9 vs. 6.1 +/- 2.1, p < 0.001). The
      aortic distensibility index and strain were statistically different in ACE DD vs.
      DI groups and DD vs. II groups of athletes. The aortic stiffness index was
      statistically different in ACE DD vs. II groups of athletes. Aortic parameters
      were similar according to ACE genotypes in controls. CONCLUSION: The results of
      this study indicate that aortic distensibility was increased by prolonged
      training in endurance athletes, particularly in those with the ACE II genotype.
      This effect represents an extracardiac adaptation to chronic prolonged training
      in athletes.

PMID- 16088129
TI  - Role of magnetic resonance imaging in the clinical diagnosis of the
      temporomandibular joint.
AB  - Temporomandibular joint (TMJ) abnormalities cannot be reliably assessed by a
      clinical examination. Magnetic resonance imaging (MRI) may depict joint
      abnormalities not seen with any other imaging method and thus is the best method
      to make a diagnostic assessment of the TMJ status. In patients with
      temporomandibular joint disorder (TMD) referred for diagnostic imaging the
      predominant TMJ finding is internal derangement related to disc displacement.
      This finding is significantly more frequent than in asymptomatic volunteers, and
      occurs in up to 80% of patients consecutively referred for TMJ imaging. Moreover,
      certain types of disc displacement seem to occur almost exclusively in TMD
      patients, namely complete disc displacements that do not reduce on mouth opening.
      Other intra-articular abnormalities may additionally be associated with the disc
      displacement, predominantly joint effusion (which means more fluid than seen in
      any asymptomatic volunteer) and mandibular condyle marrow abnormalities (which
      are not seen in volunteers). These conditions seem to be closely related. Nearly
      15% of TMD patients consecutively referred for TMJ MRI will have joint effusion,
      of whom about 30% will show bone marrow abnormalities. In a surgically selected
      material of joints with histologically documented bone marrow abnormalities
      nearly 40% showed joint effusion. Disc displacement is mostly bilateral, but
      joint effusion seems to be unilateral or with a lesser amount of fluid in the
      contralateral joint. Abnormal bone marrow is also mostly unilateral. Many
      patients have unilateral pain or more pain on one side. In a regression analysis
      the self-reported in-patient TMJ pain side difference was positively dependent on
      TMJ effusion and condyle marrow abnormalities, but negatively dependent on
      cortical bone abnormalities. Of the joints with effusion only one fourth showed
      osteoarthritis. Thus, there seems to be a subgroup of TMD patients showing more
      severe intra-articular pathology than disc displacement alone, and mostly without
      osteoarthritis. It should, however, be emphasized that patients with TMJ effusion
      and/or abnormal bone marrow in the mandibular condyle seem to constitute only a
      minor portion (less than one fourth) of consecutive TMD patients referred for
      diagnostic TMJ imaging. The majority of patients have internal derangement
      related to disc displacement, but without accompanying joint abnormalities. In
      patients with rheumatoid arthritis and other arthritides TMJ involvement may
      mimick the more common TMDs. Using MRI it is possible, in most cases, to
      distinguish these patients from those without synovial proliferation.

PMID- 16088130
TI  - Reduction of temporomandibular joint pain after treatment with a combination of
      methotrexate and infliximab is associated with changes in synovial fluid and
      plasma cytokines in rheumatoid arthritis.
AB  - The aims were to investigate the effect of intravenous infusions of the tumor
      necrosis factor-alpha (TNF-alpha) antibody infliximab on symptoms and signs of
      temporomandibular joint (TMJ) involvement in relation to effects on synovial
      fluid and plasma proinflammatory TNF-alpha, interleukin-1beta (IL-1beta) and
      interleukin-6 as well as antiinflam matory soluble TNF receptor II (TNF-sRII),
      interleukin-1 receptor antagonist (IL-1ra), soluble IL-1 receptor II (IL-1sRII)
      and interleukin-10 (IL-10) in patients with active rheumatoid arthritis (RA).
      Nineteen patients with TMJ involvement taking methotrexate were included in the
      study. TMJ and general joint pain intensity as well as pain on mandibular
      movements, tenderness to digital palpation, pressure pain threshold and maximum
      mouth-opening capacity were assessed in a clinical examination. The effect of
      infliximab was assessed after 2 and 14 or 22 weeks. TMJ synovial fluid and venous
      blood were collected for cytokine analysis at all occasions while determination
      of erythrocyte sedimentation rate and C-reactive protein were performed at
      baseline and at long-term follow-up only. Reduction of TMJ pain was associated
      with raised levels of synovial fluid TNF-sRII and IL-1sRII as well as raised
      plasma levels of IL-1ra and IL-10. Decreased erythrocyte sedimentation rate was
      associated with decreased tenderness to digital palpation. Reduced general joint
      pain intensity was associated with reduced plasma levels of IL-6 and C-reactive
      protein. In conclusion, systemic treatment with a combination of infliximab and
      methotrexate reduces TMJ pain in RA in association with an increase in anti
      inflammatory cytokines and receptors in synovial fluid and plasma.

PMID- 16088131
TI  - Sensitivity and specificity in a longitudinal temporomandibular disease study.
AB  - A longitudinal prospective study on the development of temporomandibular disease
      (TMD) in children was initiated in 1970. The study ended in 1990. One of several
      diagnostic TMD criteria applied was osteoarthrosis, defined as a 'morphological
      and/or structural deformity of the condyle' diagnosed on radiographs. Although
      these radiographic techniques are suspect in terms of falsenegative findings,
      'morphological and/or structural deformity of the condyle' has been shown to be
      associated with a characteristic craniofacial form. As such, it has confirmed
      diagnostic significance. The present study will test the reliability of this
      diagnosis using cross-sectional and longitudinal findings for objective signs and
      subjective symptoms that are attributed to TMD. Signs and symptoms of TMD
      performed poorly as predictors for 'morphological and/or structural deformity of
      the condyle'. Thirty-seven percent of the participants had a 'morphological
      and/or structural deformity of the condyle' diagnosed at least once during the 20
      year study period. In two thirds of the cases, 'morphological and/or structural
      deformity of the condyle' was not a stable characteristic through time. Normal
      radiographic anatomy of the condyle was often associated with signs and symptoms.
      We arrive at the conclusion that TMD is an umbrella, housing several overlapping
      problems that may manifest themselves at irregular intervals or even may
      disappear completely.

PMID- 16088132
TI  - Soft tissue mechanics of the temporomandibular joint.
AB  - Direct measurement of temporomandibular joint (TMJ) tissue deformation requires
      animal experimentation. Most of the available data pertain to the mechanical
      strain on the bone surfaces around the joint. However, bone is rarely the first
      joint tissue to show injury, being affected after damage to collagenous tissues
      such as the disc or capsule. Capsular ligaments guide or limit movement, while
      the intra-articular disc may also distribute joint loads. However, these tissues
      are difficult to visualize dynamically and not suitable for strain gage
      attachment, so in vivo deformations are poorly understood. Using pigs as the best
      nonprimate model for human TMJ function, we implanted differential variable
      reluctance transducers to measure antero-posterior strain in the lateral aspect
      of the intra-articular disc. The results were compared to previously published
      data on the TMJ capsule. Passive manipulation in anesthetized animals indicated
      that opening, protrusion, and contralateral movements caused the disc to
      elongate. On the contrary, closing, retrusion and ipsilateral movements caused
      disc shortening. These strains are opposite to those observed in the capsule and
      are expected on anatomical grounds. Surprisingly, disc strain during mastication
      differed from that during manipulation. The disc elongated during jaw closure,
      more on the retruding balancing side (16% +/- 1) than on the working side (8% +/-
      2). This anomalous behavior may reflect compressive loading, such that the disc
      elongates as a result of the Poisson effect rather than condylar movement.
      Because the capsule also elongates during the power stroke, especially on the
      balancing side, both disc and capsule are maximally loaded on the same side at
      the same moment.

PMID- 16088133
TI  - Anatomically based modelling of the human skull and jaw.
AB  - We present here an anatomically based model of the human masticatory system that
      provides a framework for simulating the complex chewing process. The initial
      motivation for creating this model was the desire to have a computational model
      of the human jaw that can be used to simulate the action of simple bites, and to
      calculate the stresses and forces on the teeth that are involved. The model
      created also provides a platform that can be used to investigate other features
      of the masticatory system. To construct this global model, individual models of
      the bones of the skull and jaw were created from generic data sets. Geometric
      models of the muscles of mastication were also created and attached to the
      appropriate bones. To complete this initial model, representations of the crowns
      of the teeth were created and a basic model of the temporomandibular joint (TMJ)
      was included. The finite element method was used to solve for the stresses and
      strains created by the loading conditions during a clenching simulation involving
      the mandible bone. The model presented here is also discussed in relation to a
      model of the entire musculo-skeletal system being developed as part of the
      Physiome Project.

PMID- 16088134
TI  - Modeling of temporomandibular joint function using MRI and jaw-tracking
      technologies--mechanics.
AB  - The study of mechanics of the temporomandibular joint (TMJ) is important because
      its dysfunction and breakdown could be, at least partially, of mechanical origin.
      The incongruity of the articular surfaces of the TMJ is compensated by a
      fibrocartilaginous articular disc. Its dislocation and failure seem to be closely
      related to the development of osteoarthritis of the TMJ. The analysis of
      mandibular kinematics permits the detection and assessment of irregularities of
      TMJ function due to internal obstacles such as a displaced articular disc.
      Furthermore, the measurement of the dynamic relationship between the articular
      surfaces of the TMJ is useful to determine the strains undergone by the disc that
      if too high might compromise its integrity. The development of our research in
      TMJ mechanics has evolved from the acquisition of the traces of single mandibular
      points to an accurate and compact description of mandibular motion, in which the
      mechanical advantage of jaw muscles, and forces and torques acting on the jaw are
      considered as well. The combination of three-dimensional software models of TMJ
      anatomies obtained from MRI and jaw tracking with six degrees of freedom permits
      a subject-specific dynamic analysis of the intra-articular space, providing
      insight into individual disc deformation during function and TMJ loading. Studies
      performed with this system indicate that both TMJs are loaded during chewing, the
      balancing more so than the working joint. In fact, during chewing, the intra
      articular distance is smaller for hard than for soft food, on closing than on
      opening, on the balancing than on the working side. This last finding is
      confirmed by static biting experiments, in which the condyle-fossa distance
      decreases more on the side contralateral to the bite force, depending on its
      magnitude. Also studies on the dynamics of compression areas indicate that
      plowing can occur through the disc during function, especially mediolaterally,
      due to stress field translation. This effect might contribute to cartilage wear
      and fatigue also because the disc is weaker mediolaterally. Further data indicate
      that the lateral area of the disc is mostly exposed to a higher mechanical energy
      density. This will be more intensively investigated using finite element method.

PMID- 16088135
TI  - Why look in the brain for answers to temporomandibular disorder pain?
AB  - Temporomandibular disorder (TMD) patients often exhibit widespread clinical pain,
      as well as greater sensitivity to experimental pain than pain-free controls,
      suggesting a role of central pathophysiologic mechanisms in TMD. Moreover, TMD is
      more prevalent among women, which may be related to the higher sensitivity of
      women to experimental pain. Women also exhibit greater temporal summation of heat
      pain compared to men. Temporal summation, the increase in pain intensity upon
      repetitive noxious stimulation of constant intensity, at a high frequency is
      centrally mediated. Thus, greater temporal summation in women indicates that
      their central nociceptive processing is upregulated compared to men. Recent
      studies in our research center sought further evidence for upregulation of
      central nociceptive processing in females compared to males and in TMD patients
      compared to healthy controls, assessing group differences in temporal summation
      of mechanically evoked pain, and aftersensations following repetitive noxious
      stimulation. Sixteen series of 10 repetitive, sharp, mechanical stimuli were
      applied to the fingers of 25 female TMD patients, 25 healthy women, and 25
      healthy men, with a computer-controlled small probe. All subjects rated the pain
      intensity or the unpleasantness evoked by the 1st, 5th and 10th stimulus in the
      series, and the aftersensations 15 s and 1 min after the last stimulus on visual
      analog scales. TMD patients exhibited greater temporal summation of pain and
      unpleasantness, stronger aftersensations, and more frequent painful
      aftersensations than controls. Healthy females showed greater temporal summation
      of pain intensity and unpleasantness, higher intensity and unpleasantness of
      aftersensations, and more frequent painful aftersensations than males. Greater
      temporal summation of pain and aftersensations from digital stimulation of TMD
      patients than controls suggest a generalized hyperexcitability of the central
      nociceptive system in this patient group. Such hyperexcitability may contribute
      to the development and/or maintenance of chronic TMD pain. Moreover, greater
      temporal summation of pain and aftersensations in healthy females than males
      indicate that their central processing of nociceptive input may be more easily
      upregulated into pathological hyperexcitability, possibly accounting for the
      predominance of TMD among women.

PMID- 16088136
TI  - The relation between homocysteine levels and development of Alzheimer's disease
      in mild cognitive impairment patients.
AB  - The aim of this study was to investigate over a 3-year period the connection
      between homocysteine (Hcy) levels and development of Alzheimer's disease (AD) in
      patients with mild cognitive impairment (MCI). Hcy was analyzed in 68 men, mean
      age 65 years, and 68 women, mean age 64 years. Age, sex, cobalamin, folate,
      creatinine, and thyroid profiles as well as results of Mini-Mental State
      Examination at the first visit to the memory investigation unit of a geriatric
      department were recorded from patient journals collected between 1992 and 1999.
      The total numbers of persons who converted to AD within a period of 3 years from
      initial investigation with baseline Hcy sampling was 12 of 46 (26%) males, and 18
      of 50 women (36%). The total percentage of men and women converting to AD was
      31%. Thirty-three percent of men with Hcy levels >20 micromol/l converted to AD.
      The corresponding figure for men with Hcy levels 20-17 micromol/l was 50%,
      whereas none of the 18 men with Hcy levels <17 micromol/l converted to AD. These
      differences were statistically significant. There was also a statistically
      significant difference between the percentage of women with Hcy levels >16
      micromol/l who converted to AD (45%) as compared to those with Hcy levels <16
      micromol/l who converted (21%). These findings are inconsistent with the results
      of other studies showing a positive correlation with hyperhomocysteinemia and
      occurrence of AD. However, our findings tentatively suggest a possible protective
      effect of low/normal Hcy levels on dementia conversion in MCI patients.

PMID- 16088137
TI  - Prevalence of psychiatric function disorders in psychogeriatric patients at
      referral to nursing home care--the relation to cognition, activities of daily
      living and general details.
AB  - OBJECTIVES: This prospective, observation study (from June 2001 to October 2002)
      estimated the prevalence and co-occurrence of psychiatric function disorders
      (PFDs) in psychogeriatric patients suffering from cognitive function disorders at
      referral to clinical as well as non-clinical (transmural) psychogeriatric
      programmes. It is expected that PFDs, both total and individual, are positively
      related to the cognitive function disorders as well as the activities of daily
      living (ADL) handicaps. This expectation will be adjusted for general details
      particularly gender, age, marital status, domicile and type of primary caregiver.
      Exploratively, the structure of the interrelationship of PFDs, cognitive function
      disorders and ADL handicaps will be analysed. In addition, the general details
      and the structure to be identified will be described. METHODS: We studied
      patients aged > or = 65 years (n = 487), who were suspected to suffer from
      cognitive function disorders (MMSE < or = 29) and were referred to trans
      /intramural nursing home care in the Nieuwe Waterweg Noord region. General
      details, i.e. gender, age, marital status, domicile, primary caregiver, as well
      as PFDs (the Neuropsychiatric Inventory, NPI), cognition (MMSE) and ADL (Barthel
      Index, BI) were assessed. RESULTS: Mean score NPI was 3.6 (SD = 2.3). Of the
      patients, 91.7% scored one or more NPI symptom; 81.6% two or more. Depression
      (43.9%), apathy (43.1%), anxiety (41.6%) and agitation/aggression (31.2%) had a
      high prevalence. With respect to the NPI symptoms, i.e. delusion, hallucination,
      anxiety (more in women), agitation/aggression and irritability (more in men),
      there were significant gender differences on the same MMSE level. Compared with
      women, men were significantly younger, ADL independent, lived together with their
      spouse, who was often the primary caregiver. The performance of the logistic
      regression models for total NPI score with MMSE, BI separately as well as
      combined with general details was minor. The results of the regression analyses
      for the individual NPI symptoms showed comparable low R(2) values; they explained
      a small proportion of the variance. However, in the PRINCALS analysis the MMSE
      and BI highly correlated with the cognitive dimension, and the NPI with the
      psychiatric dimension. The model fit was good; 82.6% of the variance was
      explained. CONCLUSION: At the moment of referral to nursing home care, the
      prevalence and co-occurrence of PFDs was high. The four main NPI symptoms were
      depression, apathy, anxiety and agitation/aggression. On the same level of MMSE
      score, gender difference was important for 3 NPI symptoms: delusion,
      hallucination and anxiety. NPI scores (total and per symptom) were relatively
      independent from MMSE, BI and general details. The PFDs--measured by the NPI-
      were a dimension on their own. Therefore, in psychogeriatrics it is of clinical
      relevance to think and act in terms of dimensions. Irrespective of a more
      rational psychopharmaceutical regime, this opens the door to the regular
      psychiatric domain for (psycho)therapeutic strategies, e.g. for depression and
      anxiety adapted to the kind and level of the cognitive function disorder of the
      psychogeriatric patient.

PMID- 16088138
TI  - Determinants of prestroke cognitive impairment in stroke associated with small
      vessel disease.
AB  - Understanding the determinants of prestroke cognitive impairment (PCI) in stroke
      associated with small vessel disease (SVD) may shed light on how to prevent
      further cognitive deterioration after stroke. We administered the Informant
      Questionnaire on Cognitive Decline (IQCODE) to close informants of 78 consecutive
      stroke patients who had SVD. PCI, as defined by an average score of IQCODE > or
      =3.4 was found in 19 (24%) patients. Regression analyses were performed on the
      following risk factors for PCI: age, years of education, gender, previous stroke,
      volume of white matter changes, measures of silent lacunes, cerebral atrophy
      index, medial temporal lobe atrophy and frontal lobe atrophy. Multivariate
      regression analyses revealed that only cerebral atrophy index (OR 1.5, CI 1.2
      1.9, p < 0.001) predicted PCI among patients with SVD.

PMID- 16088139
TI  - Incidence, clinical features and subtypes of delirium in elderly patients treated
      for hip fractures.
AB  - OBJECTIVE: To describe the incidence, risk factors and clinical features
      (subtypes) of delirium during the postoperative period after hip fracture surgery
      in elderly patients. DESIGN: Prospective study. METHODS: Thirty-four consecutive
      patients (9 men and 25 women) were included in this study between June 16 to July
      14, 2003. All patients underwent surgery for a fractured neck of femur and were
      pre- and postoperatively cared for at a combined geriatric/orthopedic ward.
      ASSESSMENT: The diagnosis of delirium was based on the criteria of the DSM-IV and
      the Confusion Assessment Method Scale. Subtypes of delirium were classified
      according to the criteria proposed by Lipowski: hyperactive-hyperalert (or
      agitated), hypoactive-hypoalert (somnolent) and mixed delirium. RESULTS: Fifty
      five percent (n = 19) of the 34 patients developed delirium after surgery. The
      development of delirium was associated with the medication midazolam taken
      perioperatively. Nine (47%) of the delirious patients had a hyperactive type of
      delirium; 5 (26%) developed a hypoactive delirium, and 5 (26%) had a mixed type.
      We did not find any association among subtypes of delirium and clinical features.
      CONCLUSIONS: Delirium is a common complication in the postoperative period of
      elderly patients treated for hip fractures. The use of midazolam in the
      perioperative period increased the risk of developing postoperative delirium. The
      hyperactive type of delirium was the most common subtype of delirium.

PMID- 16088140
TI  - A volumetric magnetic resonance imaging study of the amygdala in frontotemporal
      lobar degeneration and Alzheimer's disease.
AB  - The amygdala is severely atrophied at post-mortem in frontotemporal lobar
      degeneration (FTLD), and may contribute to the prominent behavioural changes that
      are early features of FTLD. The aim of this study was to assess amygdala atrophy
      using MRI in the main syndromic variants of FTLD and Alzheimer's disease (AD).
      Brain and amygdala volumes, adjusted for intracranial volume, were measured on 46
      clinically diagnosed FTLD patients [22 frontal variant FTD (FTD), 14 semantic
      dementia (SD), 10 progressive non-fluent aphasia (PNFA)], 20 AD patients, and 17
      controls. While severe amygdala atrophy was present in both FTLD (41% smaller
      than controls on the left; 33% on the right) and in AD (22% on the left; 19% on
      the right), the FTLD group had significantly greater amygdala atrophy (z = 3.21,
      p = 0.001 left, z = 2.50, p = 0.01 right) and left/right asymmetry (z = 2.03, p =
      0.04) than AD. Amygdala atrophy was greater in SD than FTD, PNFA and AD (p < 0.02
      for all). Highly asymmetrical atrophy was present in SD, greater on the left (z =
      3.23, p = 0.001), and to a lesser extent in PNFA. Despite an overlap between
      clinical and radiological features of FTLD and AD, marked amygdala atrophy points
      towards a diagnosis of FTLD, with left greater than right atrophy suggestive of
      one of the language variants.

PMID- 16088141
TI  - Prevalence of dementia among Veterans Affairs medical care system users.
AB  - OBJECTIVES: In an aging population, the number of veterans diagnosed with
      dementia is likely to increase. Knowledge of existing dementia prevalence will be
      beneficial in planning for future patient care needs. Our objectives were to
      assess the prevalence of the dementia diagnosis among those treated at Veterans
      Affairs (VA) medical centers and determine how it varies across race and Veterans
      Integrated Service Network (VISN). MATERIALS AND METHODS: Data were collected on
      all veterans seen within the VA medical system from 1997 through the first half
      of 2001. Only veterans aged 65 and over were included in the study. Veterans were
      included if they had one of the following dementia ICD-9 codes: 290.XX, 291.2,
      294.XX, 331.XX, 046.1, or 046.3. RESULTS: The overall prevalence of dementia was
      7.3%. The prevalence of dementia was similar among white patients and patients of
      other races, except African-American patients, in whom it was 50% higher. Across
      VISNs, the prevalence of dementia ranged from 5.8 to 9.4%. Alzheimer's disease
      was the most frequently diagnosed type of dementia within the VA, and inpatient
      service utilization and outpatient psychiatry visits by individuals with dementia
      were high relative to other VA patients. DISCUSSION: The overall prevalence
      identified is consistent with that reported in the literature, as is the elevated
      prevalence in African-Americans versus whites. The data on prevalence by VISN may
      identify regional variation in either the types of dementia present or the
      diagnostic criteria used. The dementia diagnosis is clearly associated with
      substantial service use.

PMID- 16088142
TI  - Cognitive impairment in the lateralized phenotype of corticobasal degeneration.
AB  - Corticobasal degeneration (CBD) is a rare disorder, which normally includes a
      combination of neurobehavioural features, movement disorders and other
      manifestations. It is now recognized that CBD patients usually present with two
      phenotypes: the lateralized phenotype and the dementia phenotype. The aim of our
      work was to determine the nature and the progression of cognitive and behavioural
      impairment in 10 lateralized CBD patients. In our patients, the most salient
      aspects of cognitive impairment were: an evident alteration of rapid alternating
      operative strategies, associated with the evident impairment of set shifting, of
      executive operations, of operative and sequential procedure and of implementation
      of judgement and abstract reasoning. The self-activation of retrieval processes
      is partly preserved in CBD. As all the other types of subcortical impairments,
      even CBD encompasses both cognitive impairment as well as a wide range of
      behaviour disturbances, such as progressive alterations of sleep, depression, and
      of anxiety (with a remarkable incidence of somatic pain). This suggests that in
      addition to neuropsychological assessment, quantification of the personality
      behaviour disorder is important for standardizing the diagnosis of subcortical
      vascular dementia and distinguishing it from any other dementias.

PMID- 16088143
TI  - Implicit and explicit memory for spatial information in Alzheimer's disease.
AB  - There is abundant evidence that memory impairment in dementia in patients with
      Alzheimer's disease (AD) is related to explicit, conscious forms of memory,
      whereas implicit, unconscious forms of memory function remain relatively intact
      or are less severely affected. Only a few studies have been performed on spatial
      memory function in AD, showing that AD patients' explicit spatial memory is
      impaired, possibly related to hippocampal dysfunction. However, studies on
      implicit spatial memory in AD are lacking. The current study set out to
      investigate implicit and explicit spatial memory in AD patients (n=18) using an
      ecologically valid computer task, in which participants had to remember the
      locations of various objects in common rooms. The contribution of implicit and
      explicit memory functions was estimated by means of the process dissociation
      procedure. The results show that explicit spatial memory is impaired in AD
      patients compared with a control group (n=21). However, no group difference was
      found on implicit spatial function. This indicates that spared implicit memory in
      AD extends to the spatial domain, while the explicit spatial memory function
      deteriorates. Clinically, this finding might be relevant, in that an intact
      implicit memory function might be helpful in overcoming problems in explicit
      processing.

PMID- 16088144
TI  - Efficacy of rivastigmine in Alzheimer's disease patients with rapid disease
      progression: results of a meta-analysis.
AB  - BACKGROUND: Alzheimer's disease (AD) patients experiencing more rapid symptom
      progression are likely to have a poorer prognosis than those experiencing slow
      symptom progression. In a recent retrospective analysis, treatment effects of
      rivastigmine were more pronounced in AD patients with rapid cognitive decline
      than in those with slow cognitive decline. This warranted further investigation.
      METHODS: Rapidly and slowly progressing patients were identified by rates of
      cognitive decline [>/=4 points and <4 points, respectively, on the Alzheimer's
      Disease Assessment Scale -- cognitive subscale (ADAS-cog)] during 26 weeks of
      placebo treatment in four randomized controlled trials (weeks 0--26). This meta
      analysis evaluated rates of cognitive decline in both subgroups during subsequent
      open-label rivastigmine 26-week extension studies (weeks 26--52). A longitudinal
      mixed effects model compared cognitive decline in rapidly and slowly progressing
      patients, including correction for possible regression to the mean. RESULTS: 180
      (75%) rapidly and 337 (78%) slowly progressing patients provided ADAS-cog data
      after 26 weeks of open-label rivastigmine treatment. Improvements in cognitive
      symptoms were observed during the first 12 weeks, which were more pronounced in
      patients with rapid progression than in those with slow progression. Rapidly
      progressing patients experienced significantly greater cognitive benefits than
      slowly progressing patients (p=0.029), who experienced a modest decline in
      cognitive symptoms at the end of the study. COMMENT: Patients experiencing rapid
      symptom progression may receive greater benefit from rivastigmine than those with
      slow progression. In this study, cholinesterase inhibition appeared to be of
      particular utility in the management of AD patients whose symptoms were rapidly
      worsening.

PMID- 16088145
TI  - Changing patient characteristics and survival experience in an Alzheimer's center
      patient cohort.
AB  - BACKGROUND: Large and diverse dementia patient cohorts can further a variety of
      research programs aimed at improving diagnosis, treatment, and meaningful
      survival in AD. METHOD: We recruited 1,502 dementia patients between 1989 and
      2002, subclassified using standardized criteria and laboratory procedures, and
      treated according to established guidelines. Baseline clinical and psychometric
      measures were repeated annually, in person or by use of a multi-modal telephone
      follow-up program that included many of the measures obtained at in-person
      visits. We tracked vital status of all subjects at 6-month intervals and offered
      autopsies to all participants. We assessed for cohort effects in baseline
      characteristics by 2-year intervals, examined the characteristics and outcomes
      for those who remained active compared to those who were eventually lost to
      follow-up, examined survival times for demographic or diagnostic subgroups, and
      assessed the accuracy of clinical diagnoses versus neuropathology. RESULTS: The
      average age at entry, average educational level, and baseline MMSE scores for
      subjects are increasing over time, and probable AD diagnoses are also increasing.
      Most (80.6%) subjects have remained active in our Center; those who did not were
      more likely to have a non-AD diagnosis. Survival averages 5.2 years (CI 4.98-
      5.37) and is influenced by age and gender, but not by diagnosis of probable
      versus possible AD. Our diagnostic accuracy is 89.6%, with high sensitivity to
      the presence of AD (96%). CONCLUSIONS: In a large and representative clinical
      cohort, the demographics of AD are changing over time. Careful analyses of those
      who continue and those who drop out from follow-up suggest that atypical
      diagnosis, rather than severity or demographic issues accounts for most of the
      attrition. Clinicians are likely to encounter increasingly older patients with
      milder disease, and these trends have implications for the design of clinical
      trials. Survival from the onset of first symptoms, similar for probable and
      possible AD cases, may be increasing over time.

PMID- 16088146
TI  - Effect of implementation of a dyspepsia and Helicobacter pylori eradication
      guideline in primary care.
AB  - BACKGROUND: Many international guidelines address appropriateness, prescribing
      variability and drug-related expenditure in primary dyspepsia management. AIMS:
      To evaluate the impact on general practitioner (GP) practice and healthcare costs
      of a participatory intervention to modify primary dyspepsia and Helicobacter
      pylori (Hp) infection management, by standardised implementation of an
      international guideline in the local setting, through a prospective, controlled
      before-and-after study. METHODS: Primary dyspepsia management was monitored in
      the Local Health District of Padua; 63 of all 354 local GPs (total patient
      population: 82,284) took part in a primary-care improvement programme. Measured
      variables were: mean prescribed gastroscopies/1,000 registered patients, mean
      expenditure/1,000 registered patients for antisecretories (H(2) blockers) and
      proton pump inhibitors (PPIs), inter-GP prescribing variability and adherence to
      guidelines, analysed through prospectively filled-out reports on GP consultations
      for dyspepsia. A 3-month pre-survey period was compared with a 6-month
      intervention period following implementation of an agreed guideline. RESULTS:
      Compared to non-participating GPs, intervention yielded a 30 and 26.4% reduction
      in H(2)-blocker and PPI expenditure, respectively. Application of the guideline
      led to an upward trend in endoscopy prescriptions, coupled with a 7% increase in
      appropriate referrals. Intra-group variability marginally decreased; guideline
      compliance rose slightly. CONCLUSIONS: Participatory intervention can reduce
      prescribing variability among GPs and inappropriate esophagogastroduodenoscopies,
      lowering related costs. Results may not have been spectacular, but in view of the
      number of patients involved, they may have an important impact on Local Health
      District expenditure.

PMID- 16088147
TI  - A classification system of echogenicity for gastrointestinal neoplasms.
AB  - BACKGROUND AND AIMS: To confirm the utility of a newly-devised endoscopic
      ultrasonography (EUS) echogenicity classification system, which is based on the
      normal five-layer structure of the gastrointestinal wall, for the differential
      diagnosis of gastrointestinal neoplasms. METHODS: A total of 275 patients with
      gastrointestinal disease detected by endoscopy, 53 with submucosal tumor (22
      esophageal, 27 gastric, and 4 duodenal), 208 with cancer (58 esophageal, 150
      gastric), and 14 with gastric malignant lymphoma, were examined. In each case, we
      performed standard EUS with 7.5, 12, or 20 MHz to evaluate the echogenicity of
      the lesion. Echogenicity was classified into seven levels that is based on the
      echogenicity of the normal five-layer structure of the gastrointestinal wall. The
      levels are stratified from anechoic (level 0) to hyperechoic (level 6),
      muscularis propria and deep mucosa being referred to as level 2 and level 4,
      respectively. Level 6 was equivalent to or higher than the echogenicity of
      submucosa. RESULTS: EUS findings revealed several distinct echogenicities among
      the diseases. In submucosal tumor, levels 0, 2, and 6 were observed only in
      patients with cyst, myogenic tumor, and lipoma, respectively. In malignancies,
      levels 0, 5, and 6 were not observed in this study. The echo level of malignant
      lymphoma was markedly lower than that of epithelial cancer. CONCLUSION: Our
      classification system of echogenicity can be a useful method in the differential
      diagnosis of gastrointestinal neoplasms.

PMID- 16088148
TI  - Consensus statement on the safety profile of topical calcineurin inhibitors.

PMID- 16088149
TI  - Gabapentin in dermatology.

PMID- 16088150
TI  - Tobacco and skin disease.

PMID- 16088151
TI  - Overexpression of c-myb in leukaemic and non-leukaemic variants of cutaneous T
      cell lymphoma.
AB  - BACKGROUND: The c-myb oncogene is a transcription factor that regulates
      proliferation, differentiation and apoptosis of haematopoietic cells and
      activated T cells by binding to promoter sequences of such genes as c-myc or bcl
      2 that are expressed in cutaneous T-cell lymphoma (CTCL). OBJECTIVE: Our study
      was performed in order to evaluate c-myb expression as a quantitative parameter
      for differential diagnosis in leukaemic and non-leukaemic variants of CTCL.
      METHODS: c-myb expression was analysed in lesional skin and in the peripheral
      blood of 21 patients with mycosis fungoides (MF), 15 patients with Sezary
      syndrome (SS) and 15 patients with inflammatory skin diseases using
      immunohistochemistry and semiquantitative as well as quantitative RT-PCR.
      RESULTS: Immunohistochemistry confirmed expression of c-myb in the lesional skin
      of the majority of CTCL patients with a tendency towards higher expression in SS
      (1.86 +/- 0.5) versus MF (1.2 +/- 0.7) while c-myb was absent from the lesional
      skin of patients with inflammatory skin diseases. c-myb was overexpressed in the
      peripheral blood in all SS patients (100% SS vs. 35.7% MF) at a high expression
      level (51,335.31 +/- 31,960.32 AU in SS vs. 1,226.35 +/- 1,258.29 AU in MF using
      semiquantitative RT-PCR, and 5.72 x 10(-2) +/- 2.27 x 10(-2) in SS vs. 0.91 x 10(
      2) +/- 1.18 x 10(-2) in MF vs. 0.24 x 10(-2) +/- 0.11 x 10(-2) in inflammatory
      skin disease using quantitative RT-PCR). CD4+ cells from the peripheral blood of
      SS patients and cell lines in vitro showed the highest c-myb expression levels
      upon quantitative RT-PCR (23.27 x 10(-2) and 10.78 x 10(-2) +/- 7.24 x 10(-2)).
      CONCLUSION: Overexpression of c-myb in skin lesions of both non-leukaemic and
      leukaemic CTCL independent of the stage of the disease indicates that it acts
      early in disease development. Nevertheless, if positive, c-myb expression in
      lesional skin is a clear-cut diagnostic marker for CTCL as compared to
      inflammatory skin diseases. High-level expression of c-myb in the peripheral
      blood as assessed by quantitative RT-PCR constitutes an additional diagnostic
      parameter for SS and may be especially useful in cases in which morphological
      determination of Sezary cells or FACS analysis of CD7 and CD26 remain
      inconclusive.

PMID- 16088152
TI  - Sun protection in renal transplant recipients: urgent need for education.
AB  - BACKGROUND: Renal transplant recipients (RTR) are considered as a high-risk group
      of skin cancer development. OBJECTIVE: The aim of the present studywas to find
      out the knowledge about the harmfulness of sunlight and the methods of sun
      protection among RTR. MATERIAL AND METHODS: 151 RTR (91 males and 60 females)
      were surveyed using a specially designed questionnaire. RESULTS: The knowledge
      about the danger of sunlight exposure among RTR appeared to be very
      unsatisfactory. Only 40.4% of patients knew that the development of skin cancer
      is connected with the exposure to sunlight. Moreover, only 68.2% of investigated
      individuals considered RTR as a high-risk group of skin cancer development.
      Although 74.8% of patients were informed about the necessity of sun protection,
      only 11.3% could explain what the number of the SPF (sun protection factor)
      means. Females significantly more often knew that RTR are especially predisposed
      to the development of skin cancers (p = 0.0001) and significantly more frequently
      could explain what the SPF number means (p = 0.006). 72.8% of RTR (females
      significantly more often, p = 0.02) made efforts to avoid sunlight irradiation.
      However, only 5.3% of the examined patients routinely used creams with SPF
      (females significantly more often, p < 0.0001). More than a half of the patients
      (62.3%) did not apply any sun protection. CONCLUSIONS: The present study revealed
      the urgent necessity of education concerning the harmfulness of sunlight and the
      methods of sun protection among RTR. Moreover, it is postulated that every
      patient should be routinely examined by a dermatologist in a dedicated transplant
      patient clinic.

PMID- 16088153
TI  - Value of direct immunofluorescence for differential diagnosis of cicatricial
      alopecia.
AB  - BACKGROUND: There are diverse causes of cicatricial alopecia characterized by
      lack of follicular ostia and irreversible loss of hair. While clinical
      differentiation between the causes may be difficult, particularly with regard to
      lichen planus (LP), lupus erythematosus (LE) and pseudopelade of Brocq (PB), it
      has been suggested that both histopathologic examination and direct
      immunofluorescence studies (DIF) are necessary for an accurate diagnosis.
      OBJECTIVE: The aim of this study was to evaluate the diagnostic value of DIF
      studies in addition to histopathology in patients with cicatricial alopecia as a
      clinical feature. METHODS: 136 scalp biopsy specimens received for histopathology
      and DIF during a 5-year period were reviewed. RESULTS: Definitive diagnosis was
      achieved by careful evaluation of scalp biopsies. The most prevalent diagnoses in
      order of frequency were LP (26%), LE (21%) and folliculitis decalvans (20%). PB
      was diagnosed in 10%. In most cases, the diagnosis could be made on the basis of
      histopathology and independently of DIF. Characteristic DIF patterns showed high
      specificity, but low sensitivity for LP, and high specificity and sensitivity for
      LE. The DIF pattern in PB showed no difference to LP. CONCLUSIONS: Histopathology
      permits diagnosis in the majority of cicatricial alopecias. DIF is of value in
      histopathologically inconclusive cases, particularly when LE is in question.

PMID- 16088154
TI  - Prognostic factor analysis for plaque psoriasis.
AB  - BACKGROUND: Little is known about the long-term prognostic factors which affect
      clinical outcomes after the diagnosis of psoriasis. OBJECTIVE: To identify the
      prognostic factors which predict long-term outcomes after diagnosis. METHODS:
      Patients' clinical characteristics at diagnosis were associated with long-term
      prognosis using the logistic regression method for 169 psoriasis patients (median
      follow-up time 11.6 years). RESULTS: The factors age > or =40 [odds ratio 0.27,
      95% confidence interval (CI) 0.10-0.72, p = 0.0091], male (odds ratio 2.67, 95%
      CI 1.02-7.00,p = 0.0459) and BMI > or =25 (odds ratio 2.74, 95% CI 1.01-7.42, p =
      0.0480) had significant effects on long-term prognosis after diagnosis. A simple
      prognostic index based on these factors was proposed. CONCLUSIONS: Three major
      prognostic factors were identified. The proposed index may be useful in the
      design of future clinical trials for psoriasis and in the selection of
      appropriate therapeutic approaches for individual patients.

PMID- 16088155
TI  - Head and neck atopic dermatitis and malassezia-furfur-specific IgE antibodies.
AB  - BACKGROUND: Atopic dermatitis of the head and neck (HNAD) has been recognized as
      a separate entity. Malassezia furfur, a lipophilic yeast, is considered to be a
      pathogenic allergen in this form of atopic dermatitis. OBJECTIVE: The purpose of
      this study was to determine the level of IgE anti-M.-furfur antibodies and their
      relation to the severity of the disease. METHODS: IgE anti-M.-furfur antibodies
      were assayed in 106 patients with HNAD. Controls included 25 patients with non
      HNAD, 20 with nonatopic dermatitis and 16 with seborrheic dermatitis (including 4
      with AIDS). RESULTS: There was a highly significant correlation between the level
      of anti-M.-furfur IgE and clinical severity. Furthermore, there was a significant
      but smaller correlation between total IgE and clinical severity. In patients with
      HNAD, total IgE was higher amongst men. CONCLUSION: IgE anti-M.-furfur antibodies
      are a good and specific marker for HNAD. IgE M. furfur levels are strongly
      correlated with the severity of the disease.

PMID- 16088156
TI  - Acne is not a stigma of HIV infection: a review of 36 patients.
AB  - INTRODUCTION: Several diseases with follicular occlusion have been described in
      HIV-infected patients and can appear isolated or associated with each other in an
      independent disease named 'HIV-associated follicular syndrome'. Worsening of
      cutaneous lesions during the course of infection in patients with previous acne
      vulgaris, late onset or severe forms of acne have been reported in HIV-infected
      patients. PATIENTS AND METHODS: A prospective study of 335 HIV-infected patients
      was performed in our hospital. A meticulous dermatological exploration in all
      patients was made, and multiple data were stored into a Microsoft Access 97
      program. Patients diagnosed as having acne were considered separately, and we
      studied their characteristics. A statistical analysis with SPSS 9.0 (Statistical
      Package for the Social Sciences) was performed. RESULTS: Thirty-six patients
      (10.8%) were diagnosed as having acne. Papulopustular lesions were the most
      frequent clinical presentation. Most lesions were localized on the face or on the
      back, and 80% of patients had mild to moderate acne; 40% of them required no
      treatment and the remainder was treated with topical measures, oral antibiotics
      and isotretinoin. 85% of cases reported the onset of acne during adolescence or
      before HIV infection and without any relationship with this disease. No relation
      between acne intensity and stage of HIV infection was observed. A multivariate
      analysis showed that the most important variable was age. DISCUSSION: In contrast
      to previous reports, no greater intensity or modifications in acne lesions were
      observed in our HIV-infected patients during the course of the disease. In the
      majority of cases, cutaneous lesions started before HIV infection, during
      adolescence, and the most important factor for suffering from acne was young age.
      In contrast to data reported in the literature, no relation of acne lesions to
      CD4 lymphocyte count or AIDS case criteria was found in our patients.
      CONCLUSIONS: Acne in HIV-infected patients has characteristics similar to those
      in non-HIV-infected patients. The age is the most important factor for the
      appearance of lesions that usually develop during adolescence. Acne lesions are
      not modified by HIV infection, and no relationship with the severity of HIV
      infection has been observed.

PMID- 16088157
TI  - Association between discoid lupus erythematosus and cigarette smoking.
AB  - BACKGROUND: Discoid lupus erythematosus (DLE) is a chronic cutaneous disease
      affecting photoexposed areas and has also been associated with cigarette smoking.
      OBJECTIVE: To evaluate the association between smoking and DLE. METHODS: A case
      control study was performed involving 57 cases diagnosed with DLE and 215 healthy
      controls. RESULTS: A higher smoking prevalence was noted in DLE cases (84.2%)
      than controls (33.5%), and the odds ratio adjusted for gender, age and
      ultraviolet index in the city of origin was 14.4 (95% confidence interval 6.2
      33.8; multiple logistic regression, p < 0.01). The cumulative smoking exposure
      was not related to premature DLE development. At the beginning of the disease,
      smokers had more extensive involvement than nonsmokers; compromise of the upper
      arms was statistically related to smoking. CONCLUSION: Cigarette smoking was
      statistically associated with DLE development. Other studies are needed in order
      to evaluate the effects of smoking cessation on the course of disease.

PMID- 16088158
TI  - Gabapentin for the symptomatic treatment of chronic neuropathic pain in patients
      with late-stage lyme borreliosis: a pilot study.
AB  - BACKGROUND: Chronic neuropathic pain occurs in 10-15% of patients with
      neuroborreliosis and is difficult to treat. OBJECTIVE: We evaluated the effect of
      gabapentin monotherapy on residual pain in patients with neuroborreliosis after
      intravenous ceftriaxone treatment. METHODS: Ten patients with neuroborreliosis
      and a long-lasting history of neurologic symptoms were treated with gabapentin,
      starting with 300 mg/day. Doses were raised over a period of 4-12 weeks to the
      individually effective and tolerated maximum dose (500-1,200 mg). Treatment was
      maintained until pain disappeared and then gradually reduced in dose over weeks.
      If symptoms recurred, the doses were raised again. Therapy was maintained over an
      average of 1-2 years. RESULTS: Pain quality and pain quantity were evaluated
      using the McGill pain questionnaire and a visual analogue scale. There was an
      improvement of 'crawling' and 'burning' pain sensations, neck and radiating
      lumbar pain in 9/10 (90%) patients as well as a positive effect on mood, general
      feeling of health and quality of sleep in 5/10 (50%) patients. The average dose
      leading to a clear-cut pain reduction was 700 mg. CONCLUSIONS: In an open pilot
      study (10 patients), gabapentin monotherapy which has to our knowledge not been
      published as treatment of chronic neuropathic pain in patients with late Lyme
      borreliosis is efficacious in treating pain associated with neuroborreliosis and
      can thus improve quality of life in these patients.

PMID- 16088159
TI  - Characterization of surfactant-induced skin damage through barrier recovery
      induced by pseudoacylceramides.
AB  - BACKGROUND AND OBJECTIVE: To determine how much barrier-reinforcing effects of
      ceramides contribute to prevent the surfactant-induced cutaneous deterioration.
      METHODS: We compared the effects of topical application of two types of
      pseudoceramides on cutaneous deterioration induced by sodium dodecyl sulfate
      (SDS) treatment for 10 days in association with alterations of barrier function.
      RESULTS: Daily application of pseudoacylceramide immediately after each SDS
      treatment significantly prevented the marked elevation of transepidermal water
      loss, which was accompanied by a marked abrogation of the increased expression in
      intercellular adhesion molecule 1 by epidermal cells as well as by suppressed
      epidermal hyperplasia. In contrast, topical application of a nonacylated
      pseudoceramide with poor barrier-reinforcing potential showed less preventive
      effects on cutaneous deterioration. CONCLUSION: These results strongly suggest
      that perturbation of the skin barrier is a causative factor in surfactant-induced
      cutaneous changes and that reinforcing the barrier function by ceramide
      application is effective in preventing the surfactant-induced skin deterioration.

PMID- 16088160
TI  - Photodynamic therapy in the treatment of rosacea.
AB  - BACKGROUND: Rosacea is a common disease, with an estimated prevalence of 5-10%.
      Established systemic and topical treatment is often effective but requires
      continuous medication. AIM: We report the outcome of photodynamic therapy (PDT)
      in 4 patients with rosacea. METHODS: Prior treatment consisted of standard
      treatment with tetracycline and metronidazole. The treatment was however either
      ineffective or the patients were dissatisfied with the need for continuous
      treatment. The patients all received standard treatment with PDT. RESULTS: The
      treated skin cleared in 3 of the 4 patients. Treatment with light alone did not
      appear to have any effect. In one of the patients there has been no relapse
      during a 9-month follow-up. In 2 patients, remissions lasted 3 months, during
      which time no additional or supplementary treatment was used. CONCLUSION: Our
      observation suggests that PDT may play a role in the future treatment of selected
      cases of rosacea.

PMID- 16088161
TI  - Cost-effectiveness of once-daily treatment with calcipotriol/betamethasone
      dipropionate followed by calcipotriol alone compared with tacalcitol in the
      treatment of Psoriasis vulgaris.
AB  - BACKGROUND: Daivobet is a once-daily treatment of psoriasis vulgaris containing
      betamethasone dipropionate and calcipotriol in a new ointment vehicle. OBJECTIVE:
      To assess the cost-effectiveness of once-daily treatment with Daivobet (4 weeks)
      followed by calcipotriol (4 weeks) compared to tacalcitol (8 weeks). METHODS:
      Resource utilization was assessed within a double-blind 8-week clinical trial
      (all treatments for psoriasis, adverse events and concomitant dermatological
      medication), estimated from the French societal perspective. RESULTS: Total
      direct medical costs for psoriasis were comparable (Daivobet: EUR 107.53 and
      tacalcitol EUR 113.50) despite a higher acquisition cost for Daivobet. The
      probability of > or =75% reduction in the Psoriasis Area and Severity Index
      (effectiveness criterion) was 46.6% with Daivobet and 13.9% with tacalcitol at 4
      weeks, and 44.6 and 23.8%, respectively, at 8 weeks (both: p < 0.001). Over 8
      weeks, Daivobet was almost twice as cost-effective as tacalcitol (EUR 241.22 per
      successful treatment vs. EUR 476.70); this result was robust to sensitivity
      assumptions. CONCLUSION: Daivobet is more effective and less costly than
      tacalcitol for treating psoriasis.

PMID- 16088162
TI  - A case of mixed bullous disease of epidermolysis bullosa acquisita and linear IgA
      bullous dermatosis.
AB  - A 75-year-old Japanese male visited us with bullous eruptions on the extremities.
      Physical examination revealed large bullae on the hands, lower legs and feet. The
      oral mucosa was also involved. Histology disclosed subepidermal blister with
      inflammatory cell infiltrates in the dermis. Direct immunofluorescence showed
      deposits of IgG and IgA at the cutaneous basement membrane zone. Indirect
      immunofluorescence on 1 M NaCl-split human skin sections demonstrated that the
      patient's IgG antibodies reacted with the dermal side of the split, while IgA
      antibodies reacted with the epidermal side. Immunoblotting showed that the
      patient's serum reacted with the NC1 domain of type VII collagen (290-kDa
      epidermolysis bullosa acquisita antigen) as well as the 120-kDa linear IgA
      bullous dermatosis antigen, LAD-1. Systemic prednisolone resulted in a favorable
      response. From the clinicopathological findings, the present case is not
      consistent with either epidermolysis bullosa acquisita or IgA bullous dermatosis.
      Therefore, we regarded the case as mixed bullous disease of epidermolysis bullosa
      acquisita and linear IgA bullous dermatosis. Such a case has not been previously
      reported.

PMID- 16088163
TI  - Cutis tricolor parvimaculata: a distinct neurocutaneous syndrome?
AB  - An 11-year-old girl had multiple, disseminated, rather small cafe-au-lait macules
      and hypochromic spots involving the neck, the trunk and the legs. In part, the
      two types of macules showed a spatial proximity, suggesting didymosis (twin
      spotting). The term cutis tricolor has been proposed to describe congenital
      paired hyperchromic and hypochromic macules on a background of intermediate skin.
      Because the spots present in this case were much smaller than those described in
      previous cases of cutis tricolor, we here propose the distinguishing term 'cutis
      tricolor parvimaculata'. The underlying gene locus may be a hot spot for
      postzygotic recombinations, giving rise to multiple twin spots. Moreover, the
      girl had developed seizures from the age of 10 years, and a large
      oligodendroglioma involving the left frontal lobe was found. A causal
      relationship between the cutaneous phenotype and the cerebral tumor is unproven
      but likely. The skin lesions were reminiscent of a disorder described by
      Westerhof et al. in 1978 under the term 'hereditary congenital hypopigmented and
      hyperpigmented macules'. So far, however, it is not clear whether cutis tricolor
      parvimaculata is identical with or different from this disorder.

PMID- 16088164
TI  - Multiple spreading epidermolytic acanthomas of the genital and perigenital skin.
AB  - Epidermolytic acanthoma is an uncommon benign tumour mainly characterized
      histologically by a prominent epidermolytic degeneration of the keratinocytes of
      the upper layers of the stratum spinosum and of the stratum granulosum. The
      absence of desmosome involvement allows to differentiate this condition from
      others such as acantholytic acanthoma. We report the first case, to our
      knowledge, of a 54-year-old male patient exhibiting disseminated scrotal,
      gluteal, inguinal and perineal epidermolytic acanthomas.

PMID- 16088165
TI  - CHILD syndrome caused by a deletion of exons 6-8 of the NSDHL gene.
AB  - The X-linked dominant CHILD syndrome (congenital hemidysplasia with ichthyosiform
      nevus and limb defects) is a rare developmental defect characterized by a
      strictly lateralized inflammatory nevus. In the majority of cases, the right side
      of the body is affected. Ipsilateral hypoplastic lesions may involve the brain,
      skeletal structures, lungs, heart or kidneys. We describe a case of CHILD
      syndrome involving the left side of the body. Absence of metacarpal, metatarsal
      and phalangeal bones of the left hand and foot resulted in oligodactyly, with
      only 3 fingers and 1 toe. An ipsilateral inflammatory epidermal nevus with
      hyperkeratosis, parakeratosis, acanthosis and perivascular lymphohistiocytic
      infiltrate was strictly confined to the left half of the patient's body. The
      phenotype was shown to be associated with a deletion of exons 6-8 of the X-linked
      NSDHL gene, confirming that CHILD syndrome is due to loss of function of an
      enzyme involved in cholesterol biosynthesis.

PMID- 16088166
TI  - Drug-induced hypersensitivity syndrome due to carbamazepine associated with
      reactivation of human herpesvirus 7.
AB  - We report a 63-year-old Japanese man with epilepsy who developed skin eruptions,
      liver dysfunction, high fever, leukocytosis and atypical lymphocytosis 4 weeks
      after he had started taking carbamazepine. Titers of human herpesvirus 7 (HHV-7)
      specific IgG antibodies were significantly increased and HHV-7 DNA was detected
      in his serum by polymerase chain reaction. These findings suggested that
      reactivation of HHV-7 could contribute to the development of drug-induced
      hypersensitivity syndrome.

PMID- 16088167
TI  - V-shaped, longitudinal nail dystrophies in trichorhinophalangeal syndrome type I.
AB  - Trichorhinophalangeal syndrome (TRPS) is a rare genodermatosis with growth
      retardation, craniofacial abnormalities, alopecia and brachyphalangia. Three
      subtypes with considerable clinical overlap can be separated. Numerous nail
      changes have been documented in this syndrome. We observed a 19-year-old female
      with typical TRPS I who developed unique V-shaped longitudinal nail dystrophies
      on both hands. TRPS belongs to the spectrum of ectodermal dysplasias, and
      therefore it is not surprising that cutaneous adnexal structures are involved in
      different ways.

PMID- 16088168
TI  - Long-term remission after 1 course of 12 weeks of alefacept therapy--a case
      report.

PMID- 16088169
TI  - Treatment of generalized granuloma annulare with hydroxychloroquine.

PMID- 16088170
TI  - Erythema multiforme induced by fluconazole.

PMID- 16088171
TI  - The role of hepatitis C virus infection in patients with chronic generalized
      pruritus.

PMID- 16088172
TI  - Hair repigmentation in a hepatitis C patient treated with interferon and
      ribavirin.

PMID- 16088173
TI  - Topical effectiveness of filgrastim in beta-thalassaemia leg ulcer.

PMID- 16088174
TI  - Immunomodulation and safety of topical calcineurin inhibitors for the treatment
      of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin
      condition that primarily affects children. Topical corticosteroids have been the
      mainstay of treatment since the late 1950s. While providing excellent short-term
      efficacy, topical corticosteroid usage is limited by potential adverse effects,
      including impairment of the function and viability of Langerhans cells/dendritic
      cells. The recently introduced topical calcineurin inhibitors pimecrolimus cream
      1% (Elidel) and tacrolimus ointment 0.03 and 0.1% (Protopic) exhibit a more
      selective mechanism of action and do not affect Langerhans cells/dendritic cells.
      For the immune system of young children 'learning' to mount a balanced Th1/Th2
      response, this selective effect has particular benefits. In clinical experience,
      topical calcineurin inhibitors have been shown to be a safe and effective
      alternative to topical corticosteroids in almost 7 million patients (>5 million
      on pimecrolimus; >1.7 million on tacrolimus). Topical pimecrolimus is primarily
      used in children with mild and moderate AD, whereas tacrolimus is used
      preferentially in more severe cases. None of the topical calcineurin inhibitors
      have been associated with systemic immunosuppression-related malignancies known
      to occur following long-term sustained systemic immunosuppression with oral
      immunosuppressants (e.g., tacrolimus, cyclosporine A, and corticosteroids) in
      transplant patients. Preclinical and clinical data suggest a greater skin
      selectivity and larger safety margin for topical pimecrolimus.

PMID- 16088175
TI  - Degree of cerebellar ataxia correlates with three-dimensional mri-based
      cerebellar volume in pure cerebellar degeneration.
AB  - The aim of the present study was to compare the severity of cerebellar ataxia as
      measured by the International Cooperative Ataxia Rating Scale (ICARS) by
      Trouillas et al. [ J Neurol Sci 1997;145:205-211] with the cerebellar volume in
      chronic cerebellar disease. Fifteen patients with pure cerebellar degeneration
      were investigated. Seven patients suffered from spinocerebellar ataxia type 6, 5
      from idiopathic late-onset cerebellar ataxia, 2 from autosomal dominant
      cerebellar ataxia type III and 1 from episodic ataxia type 2. Volumetric analysis
      was based on individual three-dimensional MR images. Total ICARS score
      significantly inversely correlated with the cerebellar volume (r = -0.805, p <
      0.0001), correlations between ICARS subscores and cerebellar volume were
      significant for upper and lower limb ataxia, ataxia of posture and gait, and
      dysarthria, but not for the oculomotor subscore. The results suggest that the
      degree of cerebellar atrophy in pure cerebellar degenerative disorders is
      accompanied by comparable functional impairment (i.e. degree of cerebellar
      ataxia).

PMID- 16088176
TI  - Assessment of potential cardiotoxic side effects of mitoxantrone in patients with
      multiple sclerosis.
AB  - Previous studies showed that mitoxantrone can reduce disability progression in
      patients with multiple sclerosis (MS). There is, however, concern that it may
      cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection
      fraction (EF) and congestive heart failure. The aim of this prospective study was
      to investigate cardiac side effects of mitoxantrone by repetitive cardiac
      monitoring in MS patients. The treatment protocol called for ten courses of a
      combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy.
      Before each course, a transthoracic echocardiogram was performed to determine the
      LV end-diastolic diameter, the end-systolic diameter and the fractional
      shortening; the LV-EF was calculated. Seventy-three patients participated (32
      males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47
      with secondary progressive and 1 with relapsing-remitting MS) who received at
      least four courses of mitoxantrone. Three of the 73 patients were excluded during
      the study (2 patients discontinued therapy; 1 patient with a previous history of
      ischemic heart disease developed atrial fibrillation after the second course of
      mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg.
      The mean follow-up time was 23.4 months (range 10-57 months). So far, there has
      been no significant change in any of the determined parameters (end-diastolic
      diameter, end-systolic diameter, fractional shortening, EF) over time during all
      follow-up investigations. Mitoxantrone did not cause signs of congestive heart
      failure in any of the patients. Further cardiac monitoring is, however, needed to
      determine the safety of mitoxantrone after longer follow-up times and at higher
      cumulative doses.

PMID- 16088177
TI  - Repair of non-circumferential cervical trachea defects by three different
      latissimus dorsi flaps. A comparative studyin an experimental setting.
AB  - BACKGROUND: Large intrathoracic airway defects may be closed using a pedicled
      latissimus dorsi (LD) flap, with rewarding results. This study addresses the
      question of whether this holds true for extrathoracic non-circumferential
      tracheal defects. METHODS: A cervical segment of the trachea of 4 x 1 cm was
      resected in 9 white male pigs. The defect was stented with a silicone stent for 3
      months and closed either by an LD flap alone (group a, n = 3), an LD flap with an
      attached rib segment covered by pleura (group b, n = 3), or an LD flap reinforced
      by a perforated polylactide (MacroPore) plate (group c, n = 3). The trachea was
      assessed by rigid endoscopy at 3 and 4 months and histologically at 4 months
      postoperatively. RESULTS: The degree of stenosis at the level of the
      reconstruction at 4 months was 25, 50 and 75% in group a, 15, 50 and 60% in group
      b, and 20, 95 and 95% in group c, respectively. The percentage of the defect
      covered by columnar epithelium was 100% in all animals of group a, 60, 100 and
      100% in group b, and 10, 0 and 0% in group c. Resorption of the rib was seen in
      all animals of group b and obstructive inflammatory polyps were found in 2
      animals of group c. CONCLUSION: Pedicled LD flaps provided less satisfactory
      results for closure of large non-circumferential extrathoracic airway defects
      than observed after intrathoracic reconstruction. A pedicled rib segment added to
      the LD flap did not improve the results obtained from LD flap repair alone, and
      an embedded MacroPore prosthesis may result in severe airway stenosis due to
      plate migration and intense inflammatory reaction protruding into the tracheal
      lumen.

PMID- 16088178
TI  - Kangaroo vs. porcine aortic valves: calcification potential after glutaraldehyde
      fixation.
AB  - The aim of this study was to evaluate and compare the calcification potential of
      kangaroo and porcine aortic valves after glutaraldehyde fixation at both low
      (0.6%) and high (2.0%) concentrations of glutaraldehyde in the rat subcutaneous
      model. To our knowledge this is the first report comparing the time-related,
      progressive calcification of these two species in the rat subcutaneous model.
      Twenty-two Sprague-Dawley rats were each implanted with two aortic valve leaflets
      (porcine and kangaroo) after fixation in 0.6% glutaraldehyde and two aortic valve
      leaflets (porcine and kangaroo) after fixation in 2% glutaraldehyde respectively.
      Animals were sacrificed after 24 h and thereafter weekly for up to 10 weeks after
      implantation. Calcium content was determined using inductively coupled plasma
      mass spectrometry and confirmed histologically. Mean calcium content per
      milligram of tissue (dry weight) treated with 0.6 and 2% glutaraldehyde was 116.2
      and 110.4 microg/mg tissue for kangaroo and 95.0 and 106.8 microg/mg tissue for
      porcine valves. Calcium content increased significantly over time (8.8 microg/mg
      tissue per week) and was not significantly different between groups. Regression
      analysis of calcification over time showed no significant difference in
      calcification of valves treated with 0.6 or 2% glutaraldehyde within and between
      the two species. Using the subcutaneous model, we did not detect a difference in
      calcification potential between kangaroo and porcine aortic valves treated with
      either high or low concentrations of glutaraldehyde.

PMID- 16088179
TI  - Ischemic preconditioning attenuates portal venous plasma concentrations of
      purines following warm liver ischemia in man.
AB  - BACKGROUND/AIMS: Degradation of adenine nucleotides to adenosine has been
      suggested to play a critical role in ischemic preconditioning (IPC). Thus, we
      questioned in patients undergoing partial hepatectomy whether (i) IPC will
      increase plasma purine catabolites and whether (ii) formation of purines in
      response to vascular clamping (Pringle maneuver) can be attenuated by prior IPC.
      METHODS: 75 patients were randomly assigned to three groups: group I underwent
      hepatectomy without vascular clamping; group II was subjected to the Pringle
      maneuver during resection, and group III was preconditioned (10 min ischemia and
      10 min reperfusion) prior to the Pringle maneuver for resection. Central, portal
      venous and arterial plasma concentrations of adenosine, inosine, hypoxanthine and
      xanthine were determined by high-performance liquid chromatography. RESULTS:
      Duration of the Pringle maneuver did not differ between patients with or without
      IPC. Surgery without vascular clamping had only a minor effect on plasma purine
      concentrations. After IPC, plasma concentrations of purines transiently
      increased. After the Pringle maneuver alone, purine plasma concentrations were
      most increased. This strong rise in plasma purines caused by the Pringle
      maneuver, however, was significantly attenuated by IPC. When portal venous minus
      arterial concentration difference was calculated for inosine or hypoxanthine, the
      respective differences became positive in patients subjected to the Pringle
      maneuver and were completely prevented by preconditioning. CONCLUSION: These data
      demonstrate that (i) IPC increases formation of adenosine, and that (ii) the
      unwanted degradation of adenine nucleotides to purines caused by the Pringle
      maneuver can be attenuated by IPC. Because IPC also induces a decrease of portal
      venous minus arterial purine plasma concentration differences, IPC might possibly
      decrease disturbances in the energy metabolism in the intestine as well.

PMID- 16088180
TI  - Application of dye-enhanced laser ablation for liver resection. Production of
      protein sealant on the cut surface of the liver by enhanced thermal energy of low
      power diode laser.
AB  - BACKGROUND: Dye-enhanced laser ablation (DLA) using a low-power diode laser for
      indocyanine green (ICG)-stained tissue has proven its effectiveness in dye
      enhanced laser photocoagulation of retinal vessels or endoscopic surgical
      mucosectomy. We have applied DLA in hepatectomy and described its histological
      distinction in comparison with the cavitron ultrasonic surgical aspirator (CUSA).
      METHODS: A diode laser (UDL-60 Laser unit, Olympus, Tokyo, Japan) with 810 +/- 20
      nm wavelength was employed for this study. The ICG dye (Diagnogreen, Daiichi
      Pharmaceutical, Tokyo, Japan) with a peak absorption wavelength at 800-810 nm was
      injected topically into the resection plane of the liver. The liver tissue was
      divided by touching the tip of the diode laser. Three different concentrations of
      ICG solution such as 2.0, 1.0 and 0.5 mg/ml were tested in the preliminary animal
      experiment. The use of a low-power diode laser at 10 W with an ICG concentration
      of 0.5 mg/ml was the appropriate combination for liver resection. In the clinical
      series, 27 hepatectomies were performed by DLA, and 10 with CUSA. RESULTS: DLA
      demonstrated smooth cutting and good hemostasis in liver resection. Among the
      hepatectomy cases given DLA, no postoperative hemorrhage or bile leakage was
      noted. The postoperative hospital stay was significantly shorter in the DLA than
      the CUSA group. The cut surface of the liver was sealed microscopically with a
      layer of protein coagulum. CONCLUSIONS: A layer of protein sealant on the cut
      surface of the liver contributes to the short postoperative hospital stay when
      using DLA.

PMID- 16088181
TI  - Commercial fibrin sealants are not equivalent in a rabbit liver-resection model
      which quantitatively evaluates hemostasis and formation of adhesions.
AB  - A rabbit partial liver resection model was used to determine the hemostatic
      effectiveness of a new fibrin sealant. Persistent bleeding, with a mean bleeding
      time of 372 s and blood loss of 18 ml, from a resected lobe of the liver was
      achieved after rabbits in the untreated control group had been infused
      continuously with unfractionated heparin over 20 min with 0.2 IU/ml at a rate of
      1 ml/min. Spraying the resected surface with the new fibrin sealant, Quixil,
      reduced bleeding to < 1 ml and the post-resection bleeding times was 25 s.
      Bleeding time, blood loss and the volume of sealant used in the rabbit model were
      inversely correlated with the thrombin concentration in the sealant. In direct
      comparisons with Tissucol and Beriplast, Quixil was associated with the shortest
      bleeding times, the lowest volume of sealant used and the lowest score of
      abdominal adhesions.

PMID- 16088182
TI  - Association of interleukin-8 and plasminogen activator system in the progression
      of colorectal cancer.
AB  - The aim of this study was to investigate the relationship of Interleukin-8 (IL-8)
      with vascular endothelial growth factor (VEGF) and plasminogen activator system
      (PA system) in the progression of colorectal cancer (CRC). In eighty-seven
      patients with CRC, the levels of IL-8, and VEGF as representative angiogenic
      factors and urokinase-type plasminogen activator (uPA), uPA receptor (uPAR),
      plasminogen activator inhibitor-1 (PAI-1), and PAI-2 as representative invasive
      factors were quantitatively assayed in tumor and adjacent normal tissues. The
      levels of IL-8, VEGF, and PA system factors in tumor tissues were all
      significantly higher than those in normal tissues. The IL-8 level was
      significantly associated with tumor size, depth of infiltration, Dukes stage, and
      liver metastasis, and also significantly correlated with the levels of VEGF,
      uPAR, uPA, and PAI-1. The VEGF level was significantly associated with tumor
      size, vascular involvement. The levels of uPAR and PAI-1 were significantly
      associated with tumor size and depth of infiltration, and the uPAR level was
      associated with liver metastasis. The VEGF level was significantly correlated
      with the levels of uPAR and PAI-1. These results reveal that IL-8, VEGF, and PA
      system factors are contributed to tumor growth, invasion, and metastasis in CRC.
      Univariate analysis revealed that high levels of IL-8, VEGF, and uPAR were
      significantly associated with a shorter overall survival time; however,
      multivariate analysis identified only liver metastasis as an independent
      prognostic factor. In conclusion, IL-8 is responsible to tumor progression and
      liver metastasis of CRC, and the activation of PAS induced by IL-8 as well as
      VEGF may play an important role in the progression of CRC.

PMID- 16088183
TI  - Effects of N-acetylcysteine on acute necrotizing pancreatitis in rats.
AB  - The aim of this study was to investigate the influence of N-acetylcysteine (NAC)
      on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats.
      The induction of ANP resulted in significant increase in mortality rate,
      pancreatic necrosis and serum activity of amylase, alanine aspartate transferase
      (ALT), interleukin-6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar
      lavage (BAL) fluid, serum concentration of urea, tissue activity of
      myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and
      significant decrease of concentrations of calcium, blood pressure, urine output
      and pO(2). The use of NAC inhibited the changes in urine output, pO(2), tissue
      activity of MPO and MDA in pancreas and lungs, and the serum activity of IL-6,
      ALT, and serum concentrations of urea and calcium. NAC reduced the mortality and
      pancreatic damage. The use of NAC has a beneficial effect on the course of ANP in
      rats. It may be used in the treatment of acute pancreatitis.

PMID- 16088184
TI  - Parity in relation to risk of axillary lymph node involvement in women with
      breast cancer. Results from Swedish population-based series of 3,472 consecutive
      cases.
AB  - OBJECTIVE: To investigate the association between parity and axillary lymph node
      involvement (ALNI) at breast cancer diagnosis. METHODS: One surgeon has reviewed
      all breast cancer cases in Malmo, Sweden, diagnosed 1961-1991. This study
      includes the 3,472 women who had a first-time diagnosis of unilateral invasive
      breast cancer, and who had undergone axillary dissection. Information was
      collected regarding date of birth, date of diagnosis, age at diagnosis,
      menopausal status, tumour size, histological type, tumour location, type of
      surgery, stage (ALNI), and parity. Parity was investigated in relation to ALNI
      using logistic regression analysis, adjusted for potential confounders, yielding
      odds ratios (OR) with 95% confidence intervals (CI). The analyses were repeated
      in different strata with regard to birth-years cohort, age at diagnosis, and
      period of diagnosis. RESULTS: High parity was associated with ALNI, the adjusted
      OR for ALNI among women with 4 or more children was 1.56 (1.13-2.15). This
      association was stronger in comparatively old women (> or = 67.45 years), OR 1.78
      (1.10-2.88). Considering parity a continuous variable, the OR for ALNI among all
      women was 1.06 (1.01-1.12). CONCLUSIONS: We conclude that women with 4 or more
      children had an increased risk of ALNI at breast cancer diagnosis.

PMID- 16088185
TI  - Surgical anatomy of the inguinal region: implications during inguinal
      laparoscopic herniorrhaphy.
AB  - INTRODUCTION: In laparoscopic inguinal hernia repair the inguinal region is
      approached and hernia repair performed from the interior side instead of the
      classical open external access. Exploration and placement of staplers in the
      internal inguinal region during laparoscopic hernia repair may sever different
      anatomical structures, or induce specific complications such as nerve entrapment,
      neuralgia, hematomas or osteitis. The incidence of these complications may be
      reduced by careful dissection of the preperitoneal tissues and by placing a
      prosthetic mesh without the use of stapling. As laparoscopic techniques evolved,
      different sizes of meshes have been used. An exact determination of mesh size was
      hitherto not investigated. AIM: Cadaver studies of the topography of blood
      vessels and nerves in the preperitoneal tissue in this region were carried out in
      order to assess a safe position and adequate size of the prosthetic mesh.
      METHODS: Dissection in 6 preserved human female cadavers was performed to define
      the actual surface of the internal inguinal region. A physical model was
      developed to formulate the ideal size of the prosthesis. Specific measurements
      were used to define the maximal size of the meshes, so as to place them without
      stapling, and without inducing neurovascular complications. RESULTS: The designed
      physical formula defines the size of the mesh as a function of the maximum intra
      abdominal pressure, the size of the abdominal wall defect and the abdominal wall
      tension. CONCLUSION: On mathematical and physical grounds our study points out
      that the size of the currently used prosthetic mesh (10 x 15 cm) is large enough
      to be placed without stapling so that with proper placement no recurrences should
      occur.

PMID- 16088186
TI  - Habitat quality and range use of white-headed langurs in Fusui, China.
AB  - The socioecology of white-headed langurs (Trachypithecus leucocephalus) was
      studied in Fusui Precious Animal Reserve, Guangxi, China, in 1997/1998. Habitat
      quality was classified according to the level of human disturbance. Plant species
      diversity increased with habitat quality. Important foods for the langurs
      occurred more in high-quality habitat. Home range size varied from 28 to 48 ha,
      and the home range area per individual decreased as habitat quality increased.
      Small polygynous langur groups had poorly defended ranges, but large groups
      defended their ranges intensively. Only harem males were involved in group
      defence, apparently competing for females by defending their habitat. High
      quality habitat was more attractive to females; accordingly, group size increased
      significantly with habitat quality.

PMID- 16088187
TI  - Behavioral development of captive male hybrid cercopithecine monkeys.
AB  - In this study, we compare the behavioral development of captive male vervet
      monkeys (Chlorocebus pygerythrus) and Sykes' monkeys (Cercopithecus albogularis)
      to male hybrids of these species. Focal animal sampling sessions were conducted
      on the study subjects from birth to 90 months of age. Behavioral categories
      (affiliative, approach, play, sexual, tension, aggressive) were plotted for each
      species and the hybrids; curves were fitted using polynomial regression and were
      evaluated with the Wilcoxon signed ranks test. With the exception of play
      behaviors, the male C. pygerythrus x C. albogularis hybrids modeled the Sykes'
      pattern of behavioral development. We suggest that this result reflects a sex
      linked paternal effect.

PMID- 16088188
TI  - Impact of methodological choices on assessments of the reliability of fossil
      primate phylogenetic hypotheses.
AB  - It has been argued in several recent studies that conventional craniodental
      characters cannot be assumed to be reliable for the purposes of reconstructing
      primate phylogenetic relationships and that as a consequence little confidence
      can be invested in published fossil primate phylogenies. Here, we evaluate this
      claim by revisiting the analyses reported in one of these studies [Collard and
      Wood, 2000]. Specifically, we investigate whether the use of alternative
      methodological procedures would have altered their findings. We focus on three
      key issues: (1) size correction, (2) outgroup composition and (3) non
      phylogenetic correlation among characters. Our analyses suggest that the results
      of Collard and Wood [2000] were not affected by the size correction method they
      used or by the outgroup they employed. Our analyses also suggest that their
      results were not affected by their decision to ignore developmental, functional
      and other non-phylogenetic correlations among the characters in their data sets.
      Accordingly, our study supports the assertion that conventional craniodental
      characters cannot be assumed to be reliable for reconstructing primate
      phylogenetic relationships. This in turn suggests that many published fossil
      primate phylogenies may be unreliable.

PMID- 16088189
TI  - Chimpanzees use tools to harvest social insects at Fongoli, Senegal.
AB  - Use of flexible probes to fish for macrotermitine termites and manufactured wands
      to dip for doriline ants is reported for a new site of chimpanzee field study.
      The flexible probes of vegetation used in termite fishing and ant dipping by the
      chimpanzees of Fongoli, in southeastern Senegal, are similar to those used at
      Assirik (Senegal) and Gombe (Tanzania). Based on the principle that form reflects
      function, we predict that ant dipping when seen will prove to be the two-handed
      technique.

PMID- 16088190
TI  - Hand-holding by Belizean black howler monkeys: intentional communication in a
      neotropical primate.

PMID- 16088191
TI  - Age-dependent activity patterns of wild male Japanese monkeys (Macaca fuscata
      yakui) on Yakushima Island.

PMID- 16088192
TI  - Eye preferences in red-capped mangabeys.

PMID- 16088193
TI  - Cytogenetic study of Lepilemur microdon.

PMID- 16088194
TI  - Altruism or cooperation in captive chimpanzees, Pan troglodytes?

PMID- 16088195
TI  - Circulating oxidized low-density lipoprotein and paraoxonase activity in
      preeclampsia.
AB  - Preeclampsia is one of the most frequent complications of pregnancy, however,
      little is known about its etiology. The objective of this study was to
      investigate the association of oxidized low-density lipoprotein (oxLDL) and
      paraoxonase (PON1) activity in women with either preeclampsia or normotensive
      (NT) pregnancy. The study groups included 41 pregnant women with preeclampsia and
      33 normotensive pregnant women. In all patients maternal serum total cholesterol
      (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and
      triglycerides (TGs) were measured using enzymatic methods. Serum PON1 activities
      and malondialdehyde (MDA) concentrations were measured by spectrophotometric
      methods, and oxLDL was measured by enzyme-linked immunoassay (ELISA). Serum
      concentrations of lipid parameters (TC, LDL, VLDL, and TGs) were significantly
      higher in preeclampsia compared with NT controls (p < 0.001, p < 0.05, p < 0.05,
      and p < 0.001, respectively). Serum concentrations of MDA and oxLDL were
      significantly higher, while PON1 activity was significantly lower in preeclampsia
      compared with NT controls (p < 0.001, p < 0.001, and p < 0.001, respectively). A
      positive correlation was detected between oxLDL and MDA (r = 0.876), and a
      negative correlation was detected between both MDA and oxLDL and PON1 (r = -0.837
      and r = -0.759, respectively). Our data demonstrate that preeclampsia is
      associated with increased oxLDL and decreased PON1 activity. Elevated oxidative
      stress, oxLDL, dyslipidemia and decreased PON1 activities may cause vascular
      endothelial damage and contribute to the pathophysiology of preeclampsia.

PMID- 16088196
TI  - Variability of nuchal translucency measurement: a multicenter study in Thailand.
AB  - OBJECTIVES: To evaluate intra- and inter-observer variations of nuchal
      translucency (NT) measurements and study the duration of measurements. SUBJECTS:
      One hundred and forty-seven singleton pregnant women with 10-14 weeks of
      gestation who had attended antenatal clinic during January 1st, 2000-August 31st,
      2001 were included. METHODS: Crown-rump length and NT were measured three times
      for each woman. Then, another examiner who was unaware of the previous results
      did the other three measurements. The duration of measurements was recorded.
      Intra-observer and inter-observer variations were analyzed by repeated ANOVA and
      paired t test, respectively. The correlation of NT measurements within each
      observer and between paired observers was evaluated by intraclass correlation
      coefficients (ICC). Kappa statistic was calculated for agreement. RESULTS: Intra
      observer variation of all 10 examiners at three institutes was varied from 0.20
      +/- 0.27 to 0.33 +/- 0.41 mm. Inter-observer variation at Chiang Mai University
      was 0.40 +/- 0.37 mm which was the highest value compared with those at Prince of
      Songkla and Khon Kaen University (p < 0.05). The mean duration of measurements
      was in range of 8-12 min. The intra-observer repeatability of the first two
      measurements showed ICCs varying from 0.61 to 0.94. The inter-observer
      repeatability of paired examiners showed a variation in ICC from 0.28-0.90. The
      kappa value expressing the intra- and inter-observer repeatability as being >95th
      or < or = 95th percentile was 0.73 and 0.72, respectively. CONCLUSIONS: NT
      measurement was reproducible for small variation and good agreement. The duration
      of measurements was acceptable.

PMID- 16088197
TI  - Risk factors for preterm birth in Korea: a multicenter prospective study.
AB  - Preterm birth is a major determinant of neonatal morbidity and mortality and
      remains one of the most serious problems in obstetrics. The aim of this study was
      to investigate the risk factors for preterm birth in Korean pregnant women. A
      total of 2,645 women were evaluated between 20 and 42 weeks' gestation at 5
      centers using a prospective study design. The patient population is limited to
      singleton gestations. Demographic factors, socioeconomic statuses, previous and
      current medical histories, complications of current gestation, and drug and
      alcohol abuse were evaluated, and univariate and multivariate logistic regression
      analyses performed. Among nulliparous women, the factors that showed a
      significant association with preterm delivery were as follows; vaginal bleeding
      during pregnancy (OR 2.6, CI 1.7-4.2), and below USD 1,000 average income (OR
      5.1, CI 1.9-13.5). The factors that showed a significant association with preterm
      delivery among multiparous women were as follows; a history of spontaneous
      abortion (OR 2.4, CI 1.1-5.2), and a history of preterm delivery (OR 3.5, CI 1.02
      11.8). In conclusion, vaginal bleeding during pregnancy, below USD 1,000 of
      average income, prior spontaneous abortion, and prior preterm delivery, were
      positively associated with preterm birth.

PMID- 16088198
TI  - Association between method of delivery and puerperal infectious complications in
      the perinatal database of Baden-Wurttemberg 1998-2001.
AB  - The strongest argument against caesarean delivery relates to maternal
      complications. Evidence supporting this for elective operations is controversial.
      The perinatal database 1998-2001 of the German state of Baden-Wurttemberg was
      studied to assess the maternal obstetrical risk associated with caesarean
      delivery with regard to puerperal infectious complications. For statistical
      analysis the chi2 test, Fisher's exact test, Mantel-Haenszel statistics and
      relative risks were used to describe the risk of exposure. Surgical delivery was
      associated with a significantly higher risk of infectious disorders (p < 0.0001).
      There was a significantly higher risk of septicaemia in the group undergoing
      caesarean compared to vaginal delivery (p < 0.0001), for pregnancies with and
      without risk factors of infection, and also for caesarean delivery prior to
      labour and rupture of membranes (ROM) and singleton gestations (RR 8.56; 95% CI
      4.4-16.65, stratum without risks). The rate of wound disorders was found to be
      significantly increased in the case of surgical delivery (p < 0.0001). After
      exclusion of pregnancies with risk factors for infectious complications and multi
      fetal gestation, a significantly higher risk was also found for caesarean
      delivery prior to labour and ROM versus vaginal delivery (RR 16.97; 95% CI 14.16
      20.34). Caesarean delivery significantly increased the likelihood that a woman
      would experience fever in puerperium (p < 0.0001), for pregnancies with and
      without ante- or perinatal risk factors for infectious complications, and also
      when caesarean delivery prior to labour and ROM and singletons in the cephalic
      presentation were considered separately (RR 11.03; 95% CI 9.39-12.96; stratum
      without risks). Considering the obstetrical challenge of how more women can
      deliver with fewer complications, reducing unnecessary caesarean delivery still
      seems to be an appropriate approach.

PMID- 16088199
TI  - Complex segregation analysis of obsessive-compulsive disorder in families with
      pediatric probands.
AB  - OBJECTIVE: The purpose of this study was to assess the mode of inheritance for
      obsessive-compulsive disorder (OCD) in families ascertained through pediatric
      probands. METHODS: We ascertained 52 families (35 case and 17 control families)
      through probands between the ages of 10 and 17 years. Direct interviews were
      completed with 215 individuals. Family informant data were collected on another
      450 individuals without direct interviews, forming two data sets with one
      contained within the other. Complex segregation analyses were performed using
      regressive models as programmed in REGTL in the S.A.G.E. package. All models used
      in the analyses included sex-specific age and type parameters. RESULTS: All
      models that excluded a residual effect of an affected parent were rejected. With
      that parameter included, the environmental and sporadic models were rejected in
      comparisons with the most general model in both data sets (all p < 0.005). With
      the direct interview data, the general codominant Mendelian model was not
      rejected when compared with the most general model (p = 0.140). We could not
      distinguish between any of the simple Mendelian models using either data set.
      However, the dominant Mendelian model provided a somewhat better fit than the
      other Mendelian models to the direct interview data. CONCLUSIONS: The results
      provide evidence for a major susceptibility locus in families with OCD when age
      at onset is incorporated into the model. Mendelian factors at most partially
      explained the familial aggregation of the phenotype, and residual familial
      effects were necessary to fit the data adequately. The results support the
      importance of linkage efforts by suggesting that a major locus is segregating
      within a proportion of families with OCD ascertained through pediatric probands.

PMID- 16088200
TI  - Macroorchidism -- marker of disease or normal variant?

PMID- 16088201
TI  - Macroorchidism in two unrelated prepubertal boys with a normal FSH receptor.
AB  - BACKGROUND: Macroorchidism in prepuberty is an uncommon condition which we
      hypothesised might reflect constitutive activation of the FSH receptor (FSHR).
      PATIENTS AND METHODS: Patient 1 was found to have macroorchidism (15 ml
      testicular volume) at the time of orchidopexy when 3.7 years of age. A gonadal
      biopsy was obtained at the time of surgery. Patient 2 developed macroorchidism (5
      ml) when 8.8 years old. Despite a testicular volume >4 ml, morning testosterone
      levels were unrecordable with no measurable gonadotrophin production in either
      patient. Patient 2 had prepubertal gonadotrophin levels 3 years later despite a
      testicular volume that was 8 ml bilaterally. Inhibin B was measured and the FSHR
      sequenced in both patients. RESULTS: Inhibin B levels were age and pubertal stage
      appropriate. Gonadal biopsy (patient 1) demonstrated areas of Sertoli cell
      hyperplasia. Sequence analysis of all 10 exons of the FSHR was normal. There was
      significant, presumed gonadotrophin-dependent testosterone production in both
      boys by 15 years of age. CONCLUSIONS: The cause of prepubertal macroorchidism in
      our patients is unclear but the pronounced difference in phenotype suggests that
      there may be more than one underlying mechanism. This mechanism was not
      constitutive activation of a mutated FSHR.

PMID- 16088202
TI  - The insulin-like growth factor system and markers of inflammation in adult
      patients with inflammatory bowel disease.
AB  - BACKGROUND AND OBJECTIVES: Catabolism and growth impairment are well-known
      complications of inflammatory bowel disease (IBD). Recent studies have
      demonstrated significant changes in the IGF system in IBD patients. The aim of
      the present study was to investigate correlations between the IGF system and
      markers of inflammation in IBD. METHODS: A cross-sectional study comprising 99
      IBD patients (Crohn's disease (CD, n = 50) and ulcerative colitis (UC, n = 49)).
      Correlations between markers of inflammation and IGF-I, IGF-II and IGFBP-3 were
      examined in CD and UC patients in remission and relapse. The patients were
      clinically scored using Crohn's Disease Activity Index (CDAI) for CD patients and
      Activity Index (AI) for UC patients. RESULTS: In the UC group we found
      correlations between IGF-I and CRP (r(s) = Spearman's rho) (r(s) = -0.40, p <
      0.01) and albumin (r(s) = 0.46, p < 0.001), IGFBP-3 and albumin (r(s) = 0.36, p <
      0.01) and AI score (r(s) = -0.31, p < 0.05). IGF-II correlated with CRP (r(s) = 
      0.42, p < 0.01), IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) = 0.41, p < 0.01),
      AI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = -0.47, p < 0.001). In
      the CD group we found correlations between IGF-I and CRP (r(s) = -0.40, p <
      0.05), and albumin (r(s) = -0.46, p < 0.01), IGFBP-3 and albumin (r = 0.36, p <
      0.01). IGF-II correlated with IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) =
      0.41, p < 0.01), CDAI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = 
      0.47, p < 0.001). CONCLUSIONS: IGF-I, IGF-II and IGFBP-3 are correlated to
      albumin and IGF-I and IGF-II are correlated to CRP in IBD patients. Further, IGF
      II is correlated to IL-6 in IBD patients. This may suggest a correlation between
      inflammation and the IGF system with involvement in muscle and bone catabolism in
      IBD.

PMID- 16088203
TI  - Primary neuroendocrine carcinoma of inguinal lymph node.
AB  - Ninety-seven percent of neuroendocrine carcinomas are located in the
      gastrointestinal tract or in the bronchopulmonary tree. Inguinal lymph nodes as
      the primary tumor site for neuroendocrine carcinoma represent a very unusual
      location, and have only been described in 2 patient series in the literature. A
      64-year-old, previously healthy, Caucasian female presented with a 2-month
      history of an enlarged inguinal lymph node on the right side. The removed lymph
      node showed histological and immunohistochemical characteristics of
      neuroendocrine differentiation (positive for synaptophysin, cytokeratin 20,
      neuron-specific enolase and chromogranin A). Although extensive investigations
      including repeated CT and NMR scans, classical endoscopy, wireless capsule
      endoscopy of the small intestine, octreotide- and MIBG scintigraphy were
      performed, no other primary tumor was found. Furthermore, there was no evidence
      of Merkel cell carcinoma on dermatological examinations. A possible explanation
      for the presence of neuroendocrine carcinomas within the lymph nodes is malignant
      transformation of preexisting intranodal epithelial nests, which have previously
      been described in lymph nodes located close to the salivary glands, thyroid
      gland, breast tissue and pancreas. Since the surgical removal of the affected
      lymph node, the patient has now been disease-free for 42 months. We therefore
      consider our case to represent a primary undifferentiated neuroendocrine
      carcinoma in an inguinal lymph node.

PMID- 16088204
TI  - Lack of adult-type salivary cortisol circadian rhythm in hospitalized preterm
      infants.
AB  - BACKGROUND/AIMS: Knowledge of the presence or absence of cortisol (F) circadian
      rhythm in preterm infants is important for the interpretation of F measurements
      made in samples taken for both clinical and research purposes. Little is known
      about its emergence in very preterm infants. This study examines circadian rhythm
      in F secretion in hospitalized infants born before 30 weeks' gestation. METHODS: 
      DESIGN: Prospective longitudinal observational study. SUBJECTS: 11 infants
      admitted consecutively and born before 30 completed weeks of gestation.
      MEASUREMENTS: F was measured by highly specific radioimmunoassay on morning and
      evening saliva samples gathered at weekly intervals until discharged home.
      Circadian rhythm was defined as > or =40% reduction from morning to evening
      level. RESULTS: For all data, the median salivary F was 10.3 nmol/l (range <0.5
      372.8). F levels were highest in the first 3 weeks of life. No infants displayed
      classical circadian rhythm for 4 weeks or more prior to being discharged from
      hospital. The other infants showed randomly distributed morning and evening F
      values with a trend in 4 infants towards periods of consistently higher evening
      than morning values. CONCLUSION: Adult-type F circadian rhythm is rarely evident
      in hospitalized preterm infants born before 30 weeks' gestation.

PMID- 16088205
TI  - Fatal disseminated cytomegalovirus infection in an infant with Cushing's syndrome
      caused by topical steroid.
AB  - Corticosteroids, even in topical application, may cause immunosuppression and
      Cushing's syndrome. A case of disseminated fatal cytomegalovirus infection is
      reported in a 3-month-old girl with Cushing's syndrome caused by exogenous
      topical clobetasol propionate application, which might have caused
      immunosuppression due to prolonged use.

PMID- 16088206
TI  - Early androgen deficiency in infants and young boys with 47,XXY Klinefelter
      syndrome.
AB  - BACKGROUND/AIMS: Klinefelter syndrome (KS) is characterized by the karyotype
      47,XXY. In this study, we evaluated the physical and testicular failure
      phenotypes of infants and young boys with KS. METHODS: The evaluation included
      auxologic measurements, biologic indices of testicular function, and clinical
      assessment of muscle tone in 22 infants and young boys with KS, ages 1-23 months.
      RESULTS: Mean length, weight, and head circumference in SDS were generally within
      the normal range at -0.3 +/- 1.0, -0.1 +/- 1.4, and 0.0 +/- 1.5, respectively.
      Mean penile length and testicular volume SDS were -0.9 +/- 0.8 and -1.1 +/- 0.8,
      indicating significantly reduced penile and testicular size. Mean testosterone
      levels for the boys < or =6 and >6-23 months were 128 +/- 131 (4.4 +/- 4.5
      nmol/l) and 9.5 +/- 7.2 ng/dl (0.3 +/- 0.2 nmol/l), respectively. High-arched
      palate was observed in 6/17 boys and clinodactyly (5th finger) was observed in
      15/16 boys. Hypotonia was evaluated clinically and was noted to be present in
      12/17 boys. CONCLUSION: The physical phenotype in infants and young boys with KS
      (1-23 months old) includes normal auxologic measurements and early evidence of
      testicular failure. Muscle tone was decreased in most of the boys. Testicular
      volume and penile length were diminished, indicating early androgen deficiency.
      The neonatal surge in testosterone was attenuated in our KS population. Thus,
      infants and young boys with KS have evidence of early testicular failure. The
      etiology of this failure and the clinical role of early androgen replacement
      require further study.

PMID- 16088207
TI  - Plant food allergies: a suggested approach to allergen-resolved diagnosis in the
      clinical practice by identifying easily available sensitization markers.
AB  - BACKGROUND: Molecular biology techniques have led to the identification of a
      number of allergens in vegetable foods, but due to the lack of purified food
      proteins for routine diagnostic use, the detection of sensitizing allergens
      remains a nearly impossible task in most clinical settings. The allergen-resolved
      diagnosis of food allergy is essential because each plant-derived food may
      contain a number of different allergens showing different physical/chemical
      characteristics that strongly influence the clinical expression of allergy;
      moreover, many allergens may cross-react with homologue proteins present in
      botanically unrelated vegetable foods. OBJECTIVE: Through a review of the
      available literature, this study aimed to detect "markers" of sensitization to
      specific plant food allergens that are easily accessible in the clinical
      practice. RESULTS: There are several "markers" of sensitization to different
      allergenic proteins in vegetable foods that can be helpful in the clinical
      practice. Specific algorithms for patients allergic to Rosaceae and to tree nuts
      were built. CONCLUSION: Clinical allergologists lacking the assistance of an
      advanced molecular biology lab may take advantage of some specific clinical data
      as well as of some "markers" in the difficult task of correctly diagnosing
      patients with plant food allergy and to provide them the best preventive advice.

PMID- 16088208
TI  - Isolation and characterization of a cDNA clone encoding one IgE-binding fragment
      of Penicillium brevicompactum.
AB  - BACKGROUND: The abundance of allergenic Penicillium species has been associated
      with an increased incidence of childhood asthma and pulmonary bleeding.
      Penicillium brevicompactum has been identified as the most prevalent indoor
      species of this genus. However, detailed studies on the allergens of the
      ubiquitous Penicillium species are still lacking. For the characterization of
      allergens of prevalent Penicillium species, molecular cloning of the allergen
      genes of P. brevicompactum was performed in the present study. METHODS: A phage
      cDNA library of P. brevicompactum was constructed in Uni-ZAP XR vector using mRNA
      isolated from the organism. The cDNA library of P. brevicompactum was screened
      using pooled atopic sera. RESULTS: Screening of P. brevicompactum cDNA library
      resulted in one positive clone encoding an estimated molecular weight of 11 kDa
      polypeptide, rich in acidic residues (>20%), with a pI of 3.87. This clone was
      designated as Pen b 26 and found to be reactive only against the atopic sera
      obtained from individuals sensitive to P. brevicompactum. The amino acid sequence
      analysis of Pen b 26 revealed that it had strong homology to the 60S acidic
      ribosomal protein P1 family from different eukaryotic sources, predominantly
      fungal aero-allergens. Other features of Pen b 26 including having high alpha
      helical content (>50%), alanine-rich residues (>20%), and a well-conserved C
      terminal epitope region fits well into the common properties of 60S acidic
      ribosomal proteins. CONCLUSIONS: The results obtained suggest that the allergenic
      clone, Pen b 26 is a 60S acidic ribosomal protein P1 of P. brevicompactum and
      shows strong similarity to other P1 family proteins.

PMID- 16088209
TI  - Detection of fish antigens aerosolized during fish processing using newly
      developed immunoassays.
AB  - BACKGROUND: Aerosolization of fish proteins during seafood processing has been
      identified as a potential route for allergic sensitization and occupational
      asthma among workers involved in high-risk activities. The aim of this study was
      to develop immunological assays for the quantification of aerosolized fish
      antigens in a fish-processing factory. METHODS: Polyclonal antibodies to the main
      fish species processed in the factory (anchovy and pilchard) were generated in
      rabbits and compared by ELISA inhibition assay and immunoblotting. These antisera
      were utilized to develop ELISA assays for the detection of fish antigens. The
      ELISA inhibition assays were evaluated by analyzing environmental air samples
      collected from three areas in a fish-processing factory: pilchard canning, fish
      meal production and lobster processing. RESULTS: By immunoblotting, the rabbit
      polyclonal antibodies demonstrated IgG antibody binding patterns comparable with
      IgE antibodies of fish-sensitized patients, particularly in regard to the major
      fish allergens parvalbumins. The sensitivity of the fish-specific ELISA assays
      developed was 0.5 microg/ml. The ELISA inhibition assays were able to
      differentiate between the two different fish species of interest but did not
      recognize a crustacean species. Notable differences in exposure levels to canned
      pilchard and anchovy antigens were demonstrated in the three different working
      areas of the factory, with assays having a detection limit as low as 105 ng/m(3).
      CONCLUSION: These ELISA-based assays are sensitive and specific to quantify
      differential exposure levels to fish antigens produced during fish processing,
      making it possible to investigate exposure-disease response relationships among
      workers in this industry.

PMID- 16088210
TI  - Antigen-induced reduction in mast cell and basophil functional responses due to
      reduced Syk protein levels.
AB  - BACKGROUND: The high-affinity IgE receptor, FcepsilonRI, is unresponsive on mast
      cells and basophils from people in several populations through an unknown
      mechanism. Similarly, FcepsilonRI-positive basophils from 'nonreleasers' are IgE
      unresponsive and are deficient in the tyrosine kinase Syk. OBJECTIVE: To test the
      hypothesis that cross-linking FcepsilonRI on mast cells and basophils leads to
      FcepsilonRI nonresponsiveness through reduction in Syk protein levels. METHODS:
      Human mast cells and basophils were used to determine if FcepsilonRI
      hyporesponsiveness correlated with reduced Syk levels. RESULTS: It is shown that
      suboptimal antigen challenge, that did not lead to significant mediator release,
      induced nonresponsiveness and correlated with reduced Syk. Other IgE-associated
      signaling molecules were unaffected by the same treatment. The ability of IgE
      unresponsive mast cells to regain FcepsilonRI responsiveness is paralleled by
      increased cellular Syk levels in vitro. The reduction of Syk levels with
      suboptimal antigen concentrations was calcium independent and mediated through a
      proteasome-dependent mechanism. CONCLUSION: These findings confirm and extend our
      knowledge about a novel regulatory mechanism for maintaining FcepsilonRI in a
      quiescent state. This mechanism may also explain why low concentrations of
      allergen given to patients during allergen immunotherapy induce FcepsilonRI
      nonresponsiveness and therapeutic benefit without inducing systemic anaphylaxis.

PMID- 16088211
TI  - Ultrastructural changes in endothelium during apoptosis indicate low microembolic
      potential.
AB  - BACKGROUND: Apoptotic endothelium has been suggested to have microthrombotic and
      microembolic potential. While some describe pro-coagulant activities and platelet
      binding, others demonstrate maintained fibrinolytic protein and anti-platelet
      aggregatory activity. Canalicular fragmentation is unique to apoptotic
      endothelium and is suggested to facilitate size reduction of apoptotic cells to
      reduce microembolic potential. Despite the potential importance of apoptotic
      microemboli, there are no reports characterizing changes in cell size and shape
      during endothelial apoptosis. METHODS: Here, we describe transmission and
      scanning electron microscopic studies of apoptotic endothelium and compare
      changes seen with apoptotic HL-60 cells incapable of canalicular fragmentation.
      RESULTS: We demonstrate reduced endothelial size (p<0.05) with progressive
      apoptosis relative to apoptotic HL-60 cells. Mechanical stress accelerated size
      reduction of apoptotic endothelium(P< 0.01) but did not affect the size of
      apoptotic HL-60 cells. Mechanical stress also increased circularity in apoptotic
      endothelium (p<0.01), suggested to facilitate passage through small vessels.
      Earlier work indicated that canaliculi form through plasma membrane invagination,
      but we report fusion of small vesicles contributing to canalicular growth, while
      canaliculi fuse to form large vacuoles and also dilate at late stages of
      apoptosis. CONCLUSIONS: These observations are consistent with the suggestion
      that endothelium is adapted to minimize microembolic potential and that
      canalicular fragmentation contributes to this.

PMID- 16088212
TI  - Decreased production of collagen Type III in cultured smooth muscle cells from
      varicose vein patients is due to a degradation by MMPs: possible implication of
      MMP-3.
AB  - An alteration of extracellular matrix is involved in varicose veins. We have
      previously shown that collagen III production, but not its mRNA expression, is
      decreased in cultured smooth muscle cells (SMC) from varicose veins, involving an
      over-production of collagen I. In this study, the mechanisms involved in this
      collagen III reduction are explored. Steady state levels of collagen III mRNA and
      its ability to translate a protein were evaluated. Neither stability nor
      functionality of the alpha1(III) coding mRNA were affected in cells from varicose
      veins. Potential intracellular degradations of collagen III were investigated
      with inhibitors of intracellular proteases but the production was unaffected. The
      level of N-terminal propeptides of collagen III in the extracellular medium was
      determined and was similar in SMC from control and varicose veins. The stability
      of collagen III was determined by time-course experiments and a degradation of
      the protein was observed in cells from varicose veins. The production of collagen
      III was partially restored in cells from varicose veins in the presence of
      Marimastat, a matrix metalloproteinase (MMP) inhibitor. The mRNA expression and
      protein production of MMP3 were increased in cells from varicose veins.
      Fibronectin, a potential substrate of MMP3, was decreased in SMC from varicose
      veins. In conclusion, collagen III, and probably fibronectin, are degraded
      extracellularly in SMC from varicose veins by a mechanism involving MMPs, and
      maybe MMP3 by a direct or an indirect pathway. The degradation of collagen III
      and fibronectin may have repercussions for the mechanical properties of the
      venous wall.

PMID- 16088214
TI  - Circulating endothelial progenitor cells and coronary collaterals in patients
      with non-ST segment elevation myocardial infarction.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) are bone marrow-derived cells
      that are augmented in response to ischemia and incorporated into
      neovascularization sites. We sought to determine whether circulating EPCs are
      related to collateral formation following non-ST segment elevation myocardial
      infarction (NSTEMI). METHODS: Twenty patients who underwent percutaneous coronary
      intervention (PCI) within a week of NSTEMI were divided into two groups: patients
      without collaterals (coll-, n=10) and patients with Rentrop grade 3--4
      collaterals (coll+, n=10). Blood samples were drawn before PCI and 24+/- 2 h
      after PCI. EPC colonies were grown from peripheral blood mononuclear cells,
      characterized, and counted. Using flow cytometry the percentage of cells co
      expressing vascular endothelial growth factor receptor-2 and CD 133 was
      determined. RESULTS: The coll+ group had higher degree of culprit vessel stenosis
      and lower initial thrombolysis in myocardial infarction flow grade. The relative
      number of EPCs before PCI was significantly higher in the coll+ group than in the
      coll- group (1.49 +/- 0.9% vs. 0.77+/- 0.4%, p= 0.045). There were no significant
      intergroup differences in the number of EPC colony-forming cells. The number of
      EPC colonies increased in the coll- group after PCI (9.5 +/- 4.8 to 14.0 +/-
      5.9/10(6) cells, p=0.01). CONCLUSIONS: This study supports an association between
      circulating EPC levels and collateral formation in patients with an NSTEMI.

PMID- 16088213
TI  - ACE inhibition lowers angiotensin-II-induced monocyte adhesion to HUVEC by
      reduction of p65 translocation and AT 1 expression.
AB  - Angiotensin-converting enzyme (ACE) inhibitors interfere with several key events
      of vascular inflammation resulting in impressive reductions in coronary vascular
      events. However, in human arteries ACE inhibitors block the production of
      angiotensin II (AngII) incompletely because of the involvement of alternative
      pathways in local AngII formation. Therefore, our study concentrated on the
      presumed modulation by ACE inhibition of local AngII-mediated inflammatory
      actions by a mechanism independent of blockage of AngII formation. We analyzed
      the effect of the ACE inhibitor ramiprilat on AngII-dependent cell adhesion
      molecule (CAM) expression and adhesion of monocytic THP-1 cells to endothelial
      cells. AngII induced upregulation of P-selectin, VCAM-1 and ICAM-1 on endothelial
      cells via activation of AT 1, which was correlated with enhanced THP-1 adhesion
      in flow chamber assays. Both enhanced adhesion and adhesion molecule expression
      were significantly reduced by pretreatment with ramiprilat. Ramiprilat reduced AT
      1 expression on endothelial cells and decreased the AngII-induced p65
      translocation into the nucleus. Diminished AT 1 expression and adhesion molecule
      expression in response to ramiprilat treatment were partially reversed after
      incubation with a bradykinin 2 receptor antagonist, suggesting that elevated
      bradykinin levels under ACE inhibition may be involved in the beneficial effect
      of ACE inhibitors. Thus, modulation of the local AngII system by ramiprilat may
      at least in part contribute to the benefits of ACE inhibition in the treatment of
      atherosclerotic diseases.

PMID- 16088215
TI  - The YedZ family: possible heme binding proteins that can be fused to transporters
      and electron carriers.
AB  - YedZ of Escherichia coli is an integral 6 transmembrane spanning (TMS) protein of
      unknown function. We have identified homologues of YedZ in bacteria and animals
      but could not find homologues in Archaea or the other eukaryotic kingdoms. YedZ
      homologues exhibit conserved histidyl residues in their transmembrane domains
      that may function in heme binding. Some of the homologues encoded in the genomes
      of magnetotactic bacteria and cyanobacteria have YedZ domains fused to transport
      and electron transfer proteins, respectively. One of the animal homologues is the
      6 TMS epithelial plasma membrane antigen of the prostate (STAMP1) that is
      overexpressed in prostate cancer. Animal homologues have YedZ domains fused C
      terminal to homologues of coenzyme F420-dependent NADP oxidoreductases. YedZ
      homologues are shown to have arisen by intragenic triplication of a 2 TMS
      encoding element. They exhibit slight but statistically significant sequence
      similarity to two families of putative heme export systems and one family of
      cytochrome-containing electron carriers. We propose that YedZ homologues function
      as heme-binding proteins that can facilitate or regulate oxidoreduction,
      transmembrane electron flow and transport.

PMID- 16088216
TI  - Production of recombinant porcine lactoferrin exhibiting antibacterial activity
      in methylotrophic yeast, Pichia pastoris.
AB  - Lactoferrin is a metal-binding glycoprotein exhibiting multifunctional
      immunoregulation of antibacterial, antioxidant, anti-endotoxin and antiviral
      activities. Uptake of porcine lactoferrin (PLF) has been shown to enhance
      resistance to diarrhea and anemia in neonatal piglets. In this study, the
      methylotrophic yeast, Pichia pastoris, was used to express a recombinant PLF
      (rPLF) gene from swine mammary gland. A synthetic secretion cassette was
      constructed using the inducible promoter of the alcohol oxidase-1 gene (AOX1) and
      the yeast alpha-mating factor signal peptide. After electroporation and Zeocin
      selection, several clones expressed high levels of rPLF protein which constitutes
      more than 30% of the total protein. A time-course study showed that rPLF mRNA
      transcripts are stably expressed during 120 h of culture induction. rPLF was
      exported into the culture supernatant at approximately 87 mg/l and a large
      portion of rPLF was accumulated in the cell cytoplasm at approximately 760 mg/l
      after 72 h of methanol induction. Recombinant PLF protein was purified via a
      heparin column using a fast protein liquid chromatography system. The
      glycosylation of P. pastoris-derived rPLF was analyzed and similar patterns to
      milk PLF were observed. Pepsin hydrolysate of rPLF displayed high bactericidal
      activity against Escherichia coli ATCC 25922 under scanning electron microscopy
      observation and minimal inhibitory concentration and minimal bactericidal
      concentration tests. Our results suggested that the methylotrophic yeast
      inducible system is suitable for large-scale production of active antibacterial
      rPLF glycoprotein.

PMID- 16088217
TI  - Insights into the genome of the enteric bacterium Escherichia blattae: cobalamin
      (B12) biosynthesis, B12-dependent reactions, and inactivation of the gene region
      encoding B12-dependent glycerol dehydratase by a new mu-like prophage.
AB  - The enteric bacterium Escherichia blattae has been analyzed for the presence of
      cobalamin (B12) biosynthesis and B12-dependent pathways. Biochemical studies
      revealed that E. blattae synthesizes B12 de novo aerobically and anaerobically.
      Genes exhibiting high similarity to all genes of Salmonella enterica serovar
      Typhimurium, which are involved in the oxygen-independent route of B12
      biosynthesis, were present in the genome of E. blattae DSM 4481. The dha regulon
      encodes the key enzymes for the anaerobic conversion of glycerol to 1,3
      propanediol, including coenzyme B12-dependent glycerol dehydratase. E. blattae
      DSM 4481 lacked glycerol dehydratase activity and showed no anaerobic growth with
      glycerol, but the genome of E. blattae DSM 4481 contained a dha regulon. The E.
      blattaedha regulon is unusual, since it harbors genes for two types of
      dihydroxyacetone kinases. The major difference to dha regulons of other enteric
      bacteria is the inactivation of the dehydratase-encoding gene region by insertion
      of a 33,339-bp prophage (MuEb). Sequence analysis revealed that MuEb belongs to
      the Mu family of bacteriophages. The E. blattae strains ATCC 33429 and ATCC 33430
      did not contain MuEb. Accordingly, both strains harbored an intact dehydratase
      encoding gene region and fermented glycerol. The properties of the glycerol
      dehydratases and the correlating genes (dhaBCE) of both strains were similar to
      other B12-dependent glycerol and diol dehydratases, but both dehydratases
      exhibited the highest affinity for glycerol of all B12-dependent dehydratases
      characterized so far. In addition to the non-functional genes encoding B12
      dependent glycerol dehydratase, the genome of E. blattae DSM 4481 contained the
      genes for only one other B12-dependent enzyme, the methylcobalamin-dependent
      methionine synthase.

PMID- 16088218
TI  - Carbonic anhydrases fused to anion transporters of the SulP family: evidence for
      a novel type of bicarbonate transporter.
AB  - The sulfate permease (SulP) family of secondary carriers (TC #2.A.53) includes
      functionally characterized members that are inorganic anion:H+ symporters and
      anion:anion antiporters. We here describe members of this family that are fused
      to non-transporter domains, a relatively rare occurrence in prokaryotes. One
      subfamily includes members that are either fused to or are encoded within operons
      that also encode homologues of carbonic anhydrases, suggesting that these
      carriers function to take up bicarbonate or carbonate. Within another subfamily,
      a SulP homologue is fused to rhodanese, a thiosulfate:cyanide sulfotransferase,
      suggesting that this carrier functions in sulfate uptake. Some homologues are
      encoded in operons that also encode putative Na+/H+ antiporters of the NhaD
      family (TC #2.A.62) or putative Na+:HCO3- symporters of the SBT family (TC
      #2.A.83). SulP homologues present in fungi and some bacteria are fused to cyclic
      AMP-binding domains and STAS domains that presumably function in regulation or
      targeting. Phylogenetic analyses reveal the relationships of these proteins and
      protein domains to each other and show that in some cases, but not in others, the
      hydrophilic domains/proteins have coevolved with the transporters.

PMID- 16088219
TI  - Biofilm-defective mutants of Bacillus subtilis.
AB  - Many bacteria can adopt organized, sessile, communal lifestyles. The gram
      positive bacterium, Bacillus subtilis,forms biofilms on solid surfaces and at air
      liquid interfaces, and biofilm development is dependent on environmental
      conditions. We demonstrate that biofilm formation by B. subtilis strain JH642 can
      be either activated or repressed by glucose, depending on the growth medium used,
      and that these glucose effects are at least in part mediated by the catabolite
      control protein, CcpA. Starting with a chromosomal Tn917-LTV3 insertional
      library, we isolated mutants that are defective for biofilm formation. The
      biofilm defects of these mutants were observable in both rich and minimal media,
      and both on polyvinylchloride abiotic surfaces and in borosilicate tubes. Two
      mutants were defective in flagellar synthesis. Chemotaxis was shown to be less
      important for biofilm formation than was flagellar-driven motility. Although
      motility is known to be required for biofilm formation in other bacteria, this
      had not previously been demonstrated for B. subtilis. In addition, our study
      suggests roles for glutamate synthase, GltAB, and an aminopeptidase, AmpS. The
      loss of these enzymes did not decrease growth or cellular motility but had
      dramatic effects on biofilm formation under all conditions assayed. The effect of
      the gltAB defect on biofilm formation could not be due to a decrease in poly
      gamma-glutamate synthesis since this polymer proved to be nonessential for robust
      biofilm formation. High exogenous concentrations of glutamate, aspartate,
      glutamine or proline did not override the glutamate synthase requirement. This is
      the first report showing that glutamate synthase and a cytoplasmic aminopeptidase
      play roles in bacterial biofilm formation. Possible mechanistic implications and
      potential roles of biofilm formation in other developmental processes are
      discussed.

PMID- 16088220
TI  - Effect of sigmaS on sigmaE-directed cell lysis in Escherichia coli early
      stationary phase.
AB  - The sigmaE regulon has been shown to perform a novel function that causes dead
      cell lysis specific to the early stationary phase in addition to its well-known
      role in the extracytoplasmic stress response in Escherichia coli. Here, the
      effect of sigmaS as a general stress-responsive sigma factor on sigmaE-directed
      cell lysis was investigated. The lysis phenomena were observed in both rpoS
      mutant and parental strains constitutively expressing active sigmaE, but the
      former lysis occurred at a relatively early stage compared to the latter. Based
      on these results and experiments with hydrogen peroxide, we propose that some
      stresses generate living but non-culturable cells, which are subject to sigmaE
      directed cell lysis.

PMID- 16088221
TI  - Cell biology of diabetic kidney disease.
AB  - In large part cellular dysfunctions induced by chronic hyperglycemia are similar
      in type-1 and -2 diabetes. In both instances chronic hyperglycemia induces injury
      to a multitude of organs by affecting various target cells. The cells affected
      may include those derived from of epithelial or mesenchymal progenitors; and at
      times hyperglycemia may induce phenotypic changes with epithelial-mesenchymal
      transformation. In the majority of target cells the high-glucose ambience
      activates various intracellular pathways that are similar except for minor
      exceptions that are related to the selective expression of various molecules in a
      given cell type. Keeping in perspective a common paradigm applicable to most of
      the cells, a brief discussion of different hyperglycemia-induced cellular events
      pertaining to various pathways is described in this review. They include fluxes
      of glucose intermediaries in various cellular metabolic pathways, generation of
      advanced glycation end products (AGEs) and their extra- and intracellular
      effects, the role of protein kinase C, transforming growth factor-beta, guanosine
      triphosphate-binding proteins and reactive oxygen species (ROS) in various
      cellular signaling events. The latter, i.e., ROS, may be central to several
      intracellular pathways and modulate various events in a reciprocal manner. The
      information compiled under various subtitles of this synopsis is derived from an
      enormous amount of literature data summarized in several recent excellent
      reviews, and thus further reading of them is suggested to gather detailed
      comprehensive information on each of the subjects.

PMID- 16088222
TI  - Neuromuscular contacts induce nitric oxide signals in skeletal myotubes in vitro.
AB  - It has previously been shown that skeletal myotubes express nitric oxide synthase
      (NOS) and produce and release NO signals. NOS is also part of agrin-induced
      acetylcholine receptor aggregations on myotubes. As nerve-muscle interactions
      underlie reciprocal signaling mechanisms, we hypothesized that NO signals in
      target myotubes may be induced by neuromuscular contacts in development. Chimeric
      neuron-myotube co-cultures were prepared using p75-selected spinal cord neurons
      from embryonic chicken. Confocal imaging revealed robust 1,2-diaminoanthraquinone
      red fluorescence indicative of de novo formation of NO only in those myotubes
      which were contacted by neurites, also verified by pre- and postsynaptic marker
      costaining (anti-synaptotagmin and alpha-bungarotoxin). Neither soluble agrin nor
      sensory dorsal root ganglionic neurons showed comparable effects in this model.
      We concluded that in target skeletal muscle cells the NOS/NO system is controlled
      by motoneuron contacts by as yet incompletely understood signaling mechanisms.
      Endogenous NO signaling in myotubes may be essential during synapse formation and
      plasticity of the neuromuscular system.

PMID- 16088223
TI  - Nogo-66 receptor at cerebellar cortical glia gap junctions in the rat.
AB  - Nogo-A is a myelin inhibitor of neurite outgrowth that accounts for the
      difficulty in fiber regeneration in the central nervous system. Its 66-amino-acid
      extracellular domain (Nogo-66) contributes to the inhibitory activity of Nogo-A.
      The Nogo-66 receptor is widely distributed in neurons of the central nervous
      system, including the cerebellum. In our study on the distribution of Nogo-66
      receptor in the cerebellar cortex in the rat, we unexpectedly found Nogo-66
      receptor immunoreactivity in the glia cells, particularly abundant beneath the
      Purkinje cells. The presence of Nogo-66 receptor in glia cells has not been
      reported before. A detailed study was thus conducted. Immunoelectron microscopic
      investigation clearly demonstrated that the Nogo-66 receptor immunoreactivity
      could be ascertained at the gap junction between glia cells, indicating that the
      Nogo-66 receptor may modulate the communication between glia cells through gap
      junctions.

PMID- 16088224
TI  - Myelination of the pig's brain: a correlated MRI and histological study.
AB  - Minipigs, 2, 4, 6 months old, were used to evaluate the relationship between
      myelination in the fiber tracts of the central nervous system (CNS) of this
      animal during development. Histological results showed an increased density of
      the myelinated fibers as well as branching of these fibers in the areas studied,
      including the cortical white matter, olfactory tract, the corticospinal tract,
      the fasciculus cuneatus and the spinal V nucleus from 2 to 6 months old. By 6
      months, the pig was sexually matured. Concomitantly, there was an increase in
      high signal-intensity regions (sites) in the magnetic resonance T(1)-weighted
      images as myelination progressed. There is a good correlation between the
      histologically observed progress of myelination and the T(1)-weighted images in
      the development of the CNS of the pig.

PMID- 16088225
TI  - Underlying mechanism of hypoxic preconditioning decreasing apoptosis induced by
      anoxia in cultured hippocampal neurons.
AB  - It is known that hypoxic preconditioning (HP, a brief period of sublethal
      hypoxia) provides neuroprotection against subsequent severe anoxia, but the
      mechanisms of this increased tolerance have not been fully elucidated. A hypoxic
      preconditioning model was established by exposing a 4-day hippocampal culture to
      1% O(2) for 20 min/day for 8 days. The preconditioning significantly decreased
      the number of apoptotic neurons at reoxygenation 24 h after 4 h of severe anoxia
      (0% O(2)). Further study demonstrated that the degradation of mitochondrial
      membrane potential (MMP) was greatly inhibited and the expression of B-cell
      lymphoma protein-2 (Bcl-2) was increased considerably after severe anoxia in the
      HP groups. These results indicate that the increased anoxic tolerance, which is
      induced by HP in cultured hippocampal cells, may be correlated with Bcl-2
      overexpression and enhanced stability of MMP, which ultimately reduces apoptosis
      24 h after reoxygenation.

PMID- 16088226
TI  - Effect of long-term exposure to constant dim light on the circadian system of
      rats.
AB  - The newly discovered multi-oscillatory nature of the mammalian circadian clock
      system and the cloning of the genes involved in the molecular mechanism that
      generates circadian rhythmicity have opened new approaches for understanding how
      mammals are temporally organized and how the mammalian circadian system reacts to
      the lack of normal synchronization cues. In the present study we investigated the
      effects of long-term exposure to constant red dim light on the pattern of the
      expression of Period 1 in the suprachiasmatic nuclei of the hypothalamus and of
      Arylalkylamine N-acetyltransferase(Aa-nat) in the retina and pineal gland. Our
      data demonstrate that Period 1 mRNA expression in the suprachiasmatic nuclei of
      the hypothalamus was not affected by exposure to constant red dim light for 60
      days, whereas Aa-nat mRNA expression in the retina and in the pineal gland was
      significantly affected, since in some animals (20-30%) Aa-nat mRNA levels were
      found to be higher during the subjective day. A circadian rhythm of serum
      melatonin and locomotor activity was present in all the animals tested. In 4
      animals serum melatonin levels were high during the subjective day. Our data
      suggest that long-term exposure to constant red dim light may induce
      desynchronization between the circadian rhythm of locomotor activity and serum
      melatonin levels.

PMID- 16088227
TI  - Age-related increase of kynurenic acid in human cerebrospinal fluid - IgG and
      beta2-microglobulin changes.
AB  - Kynurenic acid (KYNA) is an endogenous metabolite in the kynurenine pathway of
      tryptophan degradation and is an antagonist at the glycine site of the N-methyl-D
      aspartate as well as at the alpha 7 nicotinic cholinergic receptors. In the brain
      tissue KYNA is synthesised from L-kynurenine by kynurenine aminotransferases
      (KAT) I and II. A host of immune mediators influence tryptophan degradation. In
      the present study, the levels of KYNA in cerebrospinal fluid (CSF) and serum in a
      group of human subjects aged between 25 and 74 years were determined by using a
      high performance liquid chromatography method. In CSF and serum KAT I and II
      activities were investigated by radioenzymatic assay, and the levels of beta(2)
      microglobulin, a marker for cellular immune activation, were determined by ELISA.
      The correlations between neurochemical and biological parameters were evaluated.
      Two subject groups with significantly different ages, i.e. <50 years and >50
      years, p < 0.001, showed statistically significantly different CSF KYNA levels,
      i.e. 2.84 +/- 0.16 fmol/microl vs. 4.09 +/- 0.14 fmol/microl, p < 0.001,
      respectively; but this difference was not seen in serum samples. Interestingly,
      KYNA is synthesised in CSF principally by KAT I and not KAT II, however no
      relationship was found between enzyme activity and ageing. A positive
      relationship between CSF KYNA levels and age of subjects indicates a 95%
      probability of elevated CSF KYNA with ageing (R = 0.6639, p = 0.0001). KYNA
      levels significantly correlated with IgG and beta(2)-microglobulin levels (R =
      0.5244, p = 0.0049; R = 0.4253, p = 0.043, respectively). No correlation was
      found between other biological parameters in CSF or serum. In summary, a positive
      relationship between the CSF KYNA level and ageing was found, and the data would
      suggest age-dependent increase of kynurenine metabolism in the CNS. An
      enhancement of CSF IgG and beta(2)-microglobulin levels would suggest an
      activation of the immune system during ageing. Increased KYNA metabolism may be
      involved in the hypofunction of the glutamatergic and/or nicotinic cholinergic
      neurotransmission in the ageing CNS.

PMID- 16088228
TI  - Mu-opioid receptor-mediated phosphorylation of IkappaB kinase in human
      neuroblastoma SH-SY5Y cells.
AB  - Opioid receptors are involved in regulating neuronal survival. Here we
      demonstrate that activation of the mu-opioid receptor in human neuroblastoma SH
      SY5Y cells led to the phosphorylations of IkappaB kinase (IKK) and p65, denoting
      the stimulation of the nuclear factor-kappaB (NFkappaB) transcription factor.
      This response was mediated through pertussis toxin-sensitive G proteins. The mu
      opioid-induced IKK phosphorylation required extracellular signal-regulated
      protein kinase, phosphatidylinositol 3-kinase and c-Src. Moreover, c-Jun N
      terminal kinase and calmodulin-dependent kinase II also participated in the IKK
      activation, despite the lack of involvement of phospholipase Cbeta and protein
      kinase C. These data suggest that the mu-opioid receptor is capable of simulating
      NFkappaB signaling via the phosphorylation of IKK and p65 in human neuroblastoma
      SH-SY5Y cells.

PMID- 16088229
TI  - Safety considerations of adjuvant therapy in early breast cancer in
      postmenopausal women.
AB  - Because of its proven efficacy profile based on long-term data, tamoxifen has
      been the standard adjuvant endocrine therapy for hormone-sensitive early breast
      cancer for the past 30 years. However, there is well-established evidence that
      long-term use of tamoxifen is associated with serious side effects. As adjuvant
      endocrine therapy is generally administered for long periods of time, the safety
      and tolerability of agents used in this setting are of particular importance. Due
      to their superior efficacy over tamoxifen, newer agents, such as the third
      generation aromatase inhibitors (AIs), are already established therapies for the
      treatment of advanced breast cancer. In addition, recent trials indicate that the
      AI anastrozole ('Arimidex') has improved efficacy compared with tamoxifen in the
      adjuvant setting in postmenopausal women. The other third-generation AIs have
      reported disease-free survival benefits but not in the absence of prior treatment
      with tamoxifen; letrozole ('Femara') has been compared with placebo following 5
      years of tamoxifen therapy and exemestane ('Aromasin') has been compared with
      tamoxifen following 2-3 years of prior treatment with tamoxifen. Long-term safety
      data show that anastrozole also has a more favorable overall safety profile
      compared with tamoxifen, particularly in terms of life-threatening events such as
      endometrial cancer and thromboembolism. Anastrozole alone, therefore, provides a
      new option for adjuvant therapy in postmenopausal women with hormone-receptor
      positive early breast cancer. The AIs have differing pharmacological profiles,
      which may translate into dissimilar adverse event profiles in the adjuvant
      treatment setting, but patient follow-up in most trials is relatively short to
      make a valid comparison. It cannot, therefore, be assumed that all AIs will be
      equally well tolerated in the adjuvant setting. Further data on the long-term
      safety of AIs other than anastrozole are therefore required to allow overall
      risk:benefit assessments on these agents to be made.

PMID- 16088230
TI  - TC21/R-Ras2 upregulation in esophageal tumorigenesis: potential diagnostic
      implications.
AB  - OBJECTIVES: Early detection of esophageal cancer is hampered by paucity of
      molecular markers for diagnosis of this aggressive gastrointestinal malignancy in
      early stages. We recently identified TC21/R-Ras2, a small GTP-binding protein
      (SMG) in esophageal squamous cell carcinomas (ESCCs) by differential display.
      This study was designed to test the hypothesis that differential expression of
      TC21 in normal, dysplastic and malignant esophageal tissues may be of clinical
      relevance in esophageal tumorigenesis. METHODS: Immunohistochemical analysis of
      TC21 was carried out in 83 ESCCs, 37 dysplasias and 29 matched histologically
      normal esophageal tissues and correlated with clinicopathological parameters. The
      cellular localization of TC21 was determined by confocal microscopy. RESULTS:
      Expression of TC21 protein was observed in 60/83 (73%) ESCCs predominantly
      localized in tumor nuclei. Intriguingly, intense TC21 immunoreactivity was
      observed in all endoscopic biopsies with histological evidence of dysplasia (16
      cases) as well as in dysplastic areas distant to ESCCs (21 cases), while matched
      distant histologically normal epithelia did not show detectable TC21 expression.
      Immunoblotting and semi-quantitative RT-PCR confirmed TC21 expression in
      dysplastias and ESCCs. Confocal microscopy showed nuclear as well as cytoplasmic
      TC21 expression in ESCCs and TE13 cells. CONCLUSIONS: To our knowledge, this is
      the first report demonstrating differential expression of TC21 in normal,
      dysplastic and ESCC tissues, suggesting that TC21 expression is associated with
      early stages of esophageal tumorigenesis. Nuclear localization of TC21 makes it
      the third of over 100 small SMGs identified to be localized in the nucleus.

PMID- 16088231
TI  - Prospective randomized study comparing MEMID with a chop-like regimen in elderly
      patients with aggressive non-Hodgkin's lymphoma.
AB  - OBJECTIVE: This multicenter phase III study compared the MEMID regimen
      (mitoxantrone, VP16, methylglyoxal, ifosfamide and dexamethasone) with CEOP, a
      CHOP-like regimen (cyclophosphamide, epirubicin, vincristine and prednisone), in
      elderly patients (> or =65 years) with aggressive non-Hodgkin's lymphoma (NHL).
      METHODS: One hundred and forty-nine patients were eligible, 72 in the MEMID arm
      and 77 in the CEOP arm. The primary endpoint was to compare overall survival (OS)
      between groups, and secondary endpoints were event-free survival (EFS), response
      rate and toxicity. RESULTS: Neutropenia (p < 10(-5)), anemia (p < 10(-5)) and
      thrombocytopenia (p = 0.0006) were significantly more frequent in patients who
      received MEMID. We observed an objective response rate of 55.5% in the MEMID arm
      and 64.9% in the CEOP arm (p = 0.24). The median OS and EFS were 15.4 and 8.5
      months in the MEMID arm, and 20.3 and 10.5 months in the CEOP arm (p = 0.59 and
      0.47), respectively. The median EFS was 15.4 months in the MEMID arm and 20.3
      months in the CEOP arm (p = 0.59). CONCLUSION: The increased toxicity without
      survival benefit confirms the superiority of CHOP and CHOP-like regimens for
      elderly patient with aggressive NHL.

PMID- 16088232
TI  - Continuous infusion of oxaliplatin plus chronomodulated capecitabine in 5
      fluorouracil- and irinotecan-resistant advanced colorectal cancer patients.
AB  - OBJECTIVES: The aim of the study was to define the feasibility and efficacy of
      Xelox (capecitabine and oxaliplatin) administered through a new and original
      schedule in advanced pretreated colorectal cancer (CRC) patients. METHODS: 36
      metastatic CRC patients resistant at least to a previous 5-fluorouracil- and
      irinotecan-based chemotherapy line were included in the study. TREATMENT:
      Oxaliplatin 70 mg/m2 as continuous infusion for 12 h (8.00 a.m. to 8.00 p.m.) on
      days 1, 8 plus chronomodulated capecitabine 1,750 mg/m2/day per os (8.00 a.m. 25%
      of total dose; 6.00 p.m. 25% of total dose; 11.00 p.m. 50% of total dose), on
      days 1-14 every 21 days. 16 (44.4%) patients had previously received only 1
      chemotherapy line for metastatic disease and 20 patients (55.6%) 2 chemotherapy
      lines. Moreover, 12 patients (33.3%) progressed after a first or second line of
      oxaliplatin-based regimen as well. RESULTS: Most frequent related G3-4 adverse
      reactions were diarrhea (11.6%), nausea/vomiting (8.3%), neuropathy (8.3%),
      mucositis (8.3%), asthenia (16.7%) and hand-foot syndrome (5.5%). G3-4 anemia,
      leucopenia and liver toxicities were not observed. The overall response rate was
      30.6% (11/36 patients). Disease stabilization was observed in 13 patients (36.1%)
      and progression in 12 patients (34.3%). Between the 12 oxaliplatin-resistant
      patients, the overall response rate was 25% (3 patients); 6 patients (54.5%)
      obtained a stable disease, and only 3 patients (25%) progressed. The median
      overall survival was 11.3 months (95% confidence interval 7.0-15.7 months), the
      median response duration 2.8 months (95% confidence interval 1.2-5.6 months) and
      the median time to progression 6.7 months (95% confidence interval 5.7-6.3
      months). The 1-year survival rate was 53.8%. CONCLUSIONS: The high overall tumor
      growth control, the remarkable median time to progression and overall survival
      and the good safety profile are of particular interest for patients with heavy
      pretreated metastatic CRC.

PMID- 16088233
TI  - Zoledronic-acid-induced circulating level modifications of angiogenic factors,
      metalloproteinases and proinflammatory cytokines in metastatic breast cancer
      patients.
AB  - BACKGROUND: To evaluate the modifications of circulating angiogenic factors,
      metalloproteinases and acute-phase cytokines after the first single zoledronic
      acid (ZA) intravenous infusion. EXPERIMENTAL DESIGN: Eighteen consecutive breast
      cancer patients with bone metastases were evaluated for circulating levels of
      vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF),
      metalloproteinase 1 (MMP-1), metalloproteinase 2 (MMP-2), interleukins 1beta, 6
      and 8 (IL-1beta, IL-6, IL-8), interferon gamma, tumor necrosis factor alpha (TNF
      alpha) and transforming growth factor beta1 just before and 2 and 7 days after ZA
      infusion. RESULTS: The MMP-2 basal value showed a statistically significant
      decrease 48 h after ZA (p = 0.01), being at 7 days higher than the day 2 value (p
      = 0.03). The VEGF basal value showed a statistically significant decrease 48 h
      after ZA infusion (p = 0.03), increasing above the basal level at 7 days (p =
      0.07). The bFGF basal level almost significantly decreased 2 days after infusion
      (p = 0.06), being at 7 days higher than the basal value (p = 0.09). Comparing the
      day 2 values with basal ones, the linear regression model showed a significant
      positive correlation between IL-8 and bFGF (p = 0.02), IL-8 and TNF-alpha (p <
      0.0001), bFGF and TNF-alpha (p = 0.01), MMP-1 and TNF-alpha (p = 0.02).
      CONCLUSIONS: ZA could exert an antiangiogenic activity and inhibition of tumor
      cell bone invasiveness by a transient reduction of VEGF, bFGF and MMP-2
      circulating levels after infusion.

PMID- 16088234
TI  - A phase II trial of irinotecan, 5-fluorouracil and leucovorin combined with
      celecoxib and glutamine as first-line therapy for advanced colorectal cancer.
AB  - OBJECTIVES: Preclinical and clinical data indicate that cyclooxygenase-2 (COX-2)
      is a bona fide molecular target for colorectal cancer (CRC). Glutamine may
      decrease chemotherapy-associated diarrhea. This study was designed to address
      whether the addition of celecoxib, a COX-2 inhibitor, and glutamine would improve
      the efficacy and decrease the toxicities of the irinotecan, fluorouracil and
      leucovorin (IFL) regimen. METHODS: All patients received the original IFL regimen
      plus celecoxib (400 mg, po, every 12 h continuously while on trial) and glutamine
      (10 g, po, every 8 h continuously while on chemotherapy). RESULTS: Of the 41
      patients enrolled, 40 patients received between 1 and 6 cycles of treatment. This
      regimen was associated with significant toxicities: 45.0% had grade 3 diarrhea,
      35.0% grade 3/4 neutropenia, 22.5% hospitalization, 10.0% deep vein thrombosis
      and 2 treatment-related deaths. The overall response rate was 47.2%. The median
      progression-free survival was 6.7 months. The median overall survival was 16.3
      months. The 12-month overall survival rate was 54.8%. COX-2 expression was
      present in 63.2% of the specimens evaluated. There was no significant correlation
      between COX-2 expression and response to chemotherapy (p = 0.739). CONCLUSION:
      The addition of celecoxib and glutamine appears not to improve the efficacy or
      decrease the toxicities of IFL for the treatment of metastatic CRC.

PMID- 16088235
TI  - Combination of low-dose gemcitabine and recombinant quail vascular endothelial
      growth factor receptor-2 as a vaccine induces synergistic antitumor activities.
AB  - Vascular endothelial growth factor receptor-2 (VEGFR-2) has been shown to play a
      major role in inducing the full spectrum of VEGF biological response which is
      essential for tumor angiogenesis. We have demonstrated that immunotherapy of
      tumors with a vaccine based on quail homologous VEGFR-2 (qVEGFR) was effective in
      providing both protective and therapeutic antitumor immunity in several tumor
      models in mice. The purpose of this study was to determine whether the
      combination therapy of low-dose gemcitabine with qVEGFR as a vaccine could
      inhibit tumor growth to a greater extent. To test this concept, H22 hepatoma and
      Lewis lung carcinoma models were established in BALB/c mice and C57BL/6 mice,
      respectively. Mice were treated with either qVEGFR as a protein vaccine,
      gemcitabine, or both agents together. qVEGFR or low-dose chemotherapy treatment
      individually resulted in tumor inhibition to a certain extent.Remarkably, the
      combination therapy resulted in synergistic antitumor activity. Histological
      examination revealed that there was endothelial deposition of immunoglobulins
      within tumor tissues from mice treated with vaccine or combination therapy,
      especially intratumor angiogenesis was suppressed more significantly for the
      combination group. Also, ELISPOT analysis showed that mice treated with either
      qVEGFR alone or in combination with low-dose chemotherapy produced similar amount
      of anti-VEGFR antibody-producing B cells, which suggested that low-dose
      gemcitabine did not suppress the host's immune response, but potentiated the
      antitumor activity of the qVEGFR vaccine. Furthermore, TUNEL staining
      demonstrated a significant increase in the number of TUNEL-positive cells in the
      combination group compared with those of other groups. The observations may
      provide a new bio-chemotherapeutic approach for cancer.

PMID- 16088236
TI  - Phase II study of weekly paclitaxel and 24-hour infusion of high-dose 5
      fluorouracil and leucovorin in the treatment of recurrent or metastatic gastric
      cancer.
AB  - To investigate the efficacy and safety of combining weekly paclitaxel with weekly
      24-hour infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV, folinic
      acid) in the treatment of patients with advanced gastric cancer. Patients with
      histologically confirmed recurrent or metastatic gastric cancer were studied.
      Paclitaxel 80 mg/m2 3-hour intravenous infusion was given on days 1, 8, and 15,
      and high-dose 5-FU 2,600 mg/m2 plus LV 300 mg/m2 24-hour intravenous infusion
      (HDFL) was given on days 2, 9, and 16, repeated every 4 weeks. Between August
      1997 and August 2003, 30 patients were enrolled. The median age was 58 years
      (range: 37-70). Eighteen patients (60.0%) had recurrent or metastatic disease and
      12 patients had de novo metastatic disease. Among the 27 patients evaluable for
      tumor response, 2 achieved complete response and 9 achieved partial response,
      with an overall response rate of 40.7% (95% confidence interval, CI: 22-61%).
      Eleven of the 21 patients without prior exposure to HDFL-containing regimens
      responded (response rate: 52.4%, 95% CI: 29-74%), while none of the 6 patients
      who had previously failed HDFL-containing regimens responded (p value = 0.054 by
      Fisher's exact test). All 30 patients were evaluated for survival and toxicities.
      Median time to progression and overall survival were 6 and 10 months,
      respectively. Major grade 3-4 toxicities were neutropenia in 12 patients (40.0%),
      diarrhea in 10 patients (33.3%), and stomatitis in 3 patients (10.0%). Grade 1-2
      and 3-4 paclitaxel-related neuropathy developed in 16 (53.3%) and 2 (6.7%)
      patients, respectively. None of the patients discontinued protocol treatment
      because of paclitaxel-related neuropathy or developed HDFL-related hyperammonemic
      encephalopathy. This paclitaxel-HDFL regimen is effective and well tolerated in
      the treatment of advanced gastric cancer.

PMID- 16088237
TI  - Central and paracentral visual field defects and driving abilities.
AB  - The effect of central and paracentral visual field defects on driving abilities
      has until now received little attention. To date studies and surveys have
      concentrated on visual acuity and peripheral field loss. Here we summarise for
      the first time those diseases causing central visual field defects likely to be
      associated with binocular visual acuity adequate for driving.

PMID- 16088238
TI  - Comparison of achromatic and blue-on-yellow perimetry in patients with resolved
      central serous chorioretinopathy.
AB  - Central serous chorioretinopathy (CSCR) is a disorder characterized by the serous
      detachment of the sensory retina in the posterior pole. Although CSCR usually
      resolves spontaneously, the patients may notice residual visual deficits, despite
      recovering normal visual acuity. The aim of this study is to compare the blue-on
      yellow perimetric parameters with conventional automated perimetric parameters in
      the detection of visual deficits in patients with resolved CSCR. Eighteen
      patients who had spontaneous recovered from CSCR were enrolled this study. All
      subjects were examined twice with each type of perimetry. Wilcoxon test was used
      for statistical analysis. The achromatic perimetric mean deviation values were
      significantly higher in patients with CSCR than in the control group, while
      statistically a significant difference was determined for all of blue-on-yellow
      perimetric values. In conclusion the loss of central retinal sensitivity remains
      after resolution of the CSCR even if the visual acuity has recovered to normal.
      Blue-on-yellow perimetry is more sensitive than achromatic perimetry to reveal
      this central sensitivity loss.

PMID- 16088239
TI  - Vitrectomy for diabetic macular edema with and without internal limiting membrane
      removal.
AB  - PURPOSE: To compare the efficacy of surgically removing or not removing the
      internal limiting membrane (ILM) during pars plana vitrectomy on the visual
      acuity and retinal thickness in eyes with diabetic macular edema. METHODS: A
      prospective, case-control study was carried out on 30 eyes of 29 patients
      undergoing pars plana vitrectomy for diabetic macular edema. Fifteen eyes
      underwent pars plana vitrectomy with ILM removal and 15 eyes without ILM removal.
      RESULTS: In 7 of 15 eyes (47%) in the ILM-removed group, the visual acuity
      improved by 0.2 or more log of the minimum angle of resolution (log MAR) units
      and remained unchanged in 8 eyes (53%). In the ILM-preserved group, the final
      visual acuity improved in 9 of 15 eyes (60%) and remained unchanged in 6 eyes
      (40%). The difference in visual acuity between the two groups after 11 months the
      surgery was not significant (Fisher's exact test, p=0.4938). In the ILM-removed
      group, the final retinal thickness decreased by more than 20% of the preoperative
      retinal thickness in 12 of 15 eyes (80%), remained unchanged in 2 of 15 eyes
      (13%), and increased in 1 of 15 eyes (7%). In the ILM-preserved group, the final
      retinal thickness decreased in 13 of 15 eyes (87%) and remained unchanged in 2 of
      15 eyes (23%). The differences in the changes in the retinal thickness between
      the two groups were not statistically significant (Fisher's exact test,
      p=0.5945). CONCLUSION: Vitrectomy in eyes with diabetic macular edema without ILM
      removal was as effective in reducing the retinal thickness and improving the
      visual acuity as eyes with ILM removal. We conclude that ILM need not be removed
      to treat eyes with diabetic macular edema.

PMID- 16088240
TI  - Activated STAT 3 in choroidal neovascular membranes of patients with age-related
      macular degeneration.
AB  - PURPOSE: The Jak/STAT (Janus tyrosine kinase/signal transducers and activators of
      transcription) pathway is critical for growth control, developmental regulation
      and homeostasis. Here we studied the expression of STAT proteins in the
      proliferative disease of age-related macular degeneration (AMD) with choroidal
      neovascular membranes (CNVM). The STAT family are of cytoplasmic proteins with
      roles as signal messengers and transcription factors that participate in normal
      cellular responses to cytokines and growth factors. Abnormal activity of certain
      STAT family members, particularly STAT 3 and STAT 5, is associated with a wide
      variety of human malignancies and other diseases. Here were studied STAT
      activation in CNVM of patients with AMD. METHODS: Sections of formalin-fixed,
      paraffin-embedded samples from 8 eyes with AMD and 5 controls were included in
      this study. Immunohistochemical staining was performed using antibodies against
      activated STAT 1, STAT 3 and STAT 5 proteins, and tenascin. RESULTS: In CNVM, we
      observed a strong positive staining for tenascin and STAT 3 in retinal pigmented
      epithelial (RPE) cells restricted to areas of developing scars. In contrast, STAT
      3 immunoreactivity failed in areas completely composed of fibrovascular disciform
      scar material. In addition, no immunoreactivity for both STAT 1 and STAT 5 was
      detected in all CNVM and in all control samples. CONCLUSION: In CNVM, activation
      of STAT 3 appears in RPE cells simultaneously with the formation of scars.

PMID- 16088241
TI  - Transforming growth factor beta(2) increases in subretinal fluid in
      rhegmatogenous retinal detachment with subretinal strands.
AB  - PURPOSE: To compare transforming growth factor (TGF) beta(2) levels in subretinal
      fluid of rhegmatogenous retinal detachment with or without subretinal strand
      formation. METHODS: We assessed total and mature TGF-beta(2) levels in subretinal
      fluid obtained from 24 eyes with rhegmatogenous retinal detachment using an
      enzyme-linked immunosorbent assay. Group I comprised 18 specimens from eyes
      without subretinal strands, while group II comprised 6 specimens from eyes with
      subretinal strands. RESULTS: Total and mature TGF-beta(2) levels were higher in
      group II than in group I (p=0.01 and p=0.07, respectively). CONCLUSION: The
      concentrations of total and mature TGF-beta(2) were higher in cases of
      rhegmatogenous retinal detachment associated with subretinal strand formation
      compared to those without subretinal strand formation.

PMID- 16088242
TI  - Congenital growth hormone deficiency and eye refraction: a longitudinal study.
AB  - The aim of this study was to study the influence of growth hormone deficiency
      (GHD) on emmetropization and to evaluate the effect of growth hormone replacement
      therapy on eye refraction. Twenty-eight children affected by congenital GHD and
      undergoing substitutive therapy (group 1), and 28 healthy subjects (group 2),
      were prospectively studied. All patients had a thorough eye examination,
      including cycloplegic refraction and axial length measurement (only GHD
      children). After 2 years, we found in both groups a reduction of the dioptric
      power of the eye. A t test for paired data showed statistically significant
      differences in both groups (p<0.001), but the change of refraction was higher in
      group 2 (p<0.01). Axial length showed a statistically significant increase,
      according to the myopic shift (p<0.001). The change of the refraction found in
      GHD children could be related to the somatic growth and partially induced by
      growth hormone therapy. The difference between the two groups could be explained
      with the late beginning of the therapy in GHD children. It is possible to form
      the hypothesis that a correct and well-timed substitutive therapy could permit a
      normal emmetropization process.

PMID- 16088243
TI  - The Relationship between chlamydia trachomatis and chlamydia pneumoniae as the
      cause of neonatal conjunctivitis (ophthalmia neonatorum).
AB  - The authors examined 130 newborns and nursery children from September 1999 till
      May 2003 from the Prague district for the surmise of chlamydial conjunctivitis.
      Chlamydia infections were detected in conjunctival smears. Chlamydia trachomatis
      was confirmed in 20 (15.3%) using ligase chain reaction and C. pneumoniae in 16
      (12.3%) children using an indirect immunofluorescent method. Direct captures of
      chlamydial infections of newborns were included in the study. The authors had
      also examined 671 newborns in a maternity hospital from January 2002 till May
      2003. Conjunctival scraping had been done in 29 (4.3%) cases mainly for
      mucopurulent conjunctivitis. Chlamydial conjunctivitis was identified only in 4
      (0.6%) cases, i.e. C. trachomatis and C. pneumoniae in 2 cases each. Initial
      clinical symptoms of both types of chlamydial conjunctivitis were similar (mucous
      discharge with various degrees of eyelid effusion and chemosis mainly on the
      tarsal conjunctiva). Clinical symptoms of the C. pneumoniae infection were later
      accompanied by pseudofollicular changes on the tarsal conjunctiva. The
      complication of this infection was lacrimal obstruction among half of newborns.
      Clarithromycin in syrup at a dose of 15 mg/kg/per day for 14 days ensured
      effective treatment of both chlamydial infections. Control scrapings were always
      negative and simultaneously the pathological conjunctival finding disappeared.

PMID- 16088244
TI  - Long-term outcome of patients with large overcorrection following surgery for
      exotropia.
AB  - To provide long-term surgical results for patients with large initial
      overcorrection following surgery for exodeviation, 68 consecutive patients with
      initial overcorrection of 20 prism diopters (PD) or more at distance or near
      following surgery for exodeviation performed between 1994 and 2002 were included
      in this study. The patients were managed with an alternate full-time occlusion,
      echothiophate iodide, or prism glasses for the period of overcorrection. One day
      postoperatively, the amount of overcorrection was 8--40 PD at distance and 0--35
      PD at near, and decreased to 10 PD or less both at distance and near vision
      within 4 weeks postoperatively in 49 patients (72%). Seven patients needed prism
      glasses for esotropia of less than 10 PD. Four patients (5.9%) needed a
      reoperation for consecutive esotropia and 1 patient for postoperative hypotropia
      following recession of the superior and lateral rectus. The final outcome showed
      orthophoria to exo/esodeviation of <or=10 PD in 48 patients (71%) and
      exodeviations of >10 PD in 11 patients (16%) at near or distance. In conclusion,
      overcorrection was reduced to 10 PD or less at distance and near within 4 weeks
      after surgery in most patients. Even with initial overcorrection of 20 PD or more
      after surgery for exodeviation, reoperation for consecutive esotropia was
      necessary only in 5.9% of the patients.

PMID- 16088245
TI  - Risk of retinal vein occlusions in patients treated with rofecoxib (vioxx).
AB  - AIMS: To present patients with branch retinal vein occlusion (BRVO) and central
      retinal vein occlusion (CRVO) after application of rofecoxib (Vioxx), a cyclo
      oxygenase (COX) 2 inhibitor. METHODS: Three patients with sudden decrease in
      their vision were referred for evaluation and possible treatment. RESULTS: A 72
      year-old female with rheumatoid arthritis was treated with rofecoxib. When the
      dosage was doubled to 50 mg daily, she noticed a sudden painless decrease of
      vision in her right eye. Her visual acuity (VA) was 20/400 OD and 20/20 OS.
      Biomicroscopy OD demonstrated a CRVO with tortuous retinal veins and numerous
      flecked hemorrhages in the midperiphery. A 68-year-old female with severe
      osteoporosis developed a BRVO with flame-shaped hemorrhages in the superior
      hemisphere OS 1 day after taking rofecoxib (25 mg) daily. A 47-year-old American
      male took Vioxx for 1 week to relieve hip pain and noticed temporarily decreased
      vision OD. A month later, he resumed taking Vioxx and noticed a progressive
      decline in his VA with persistent cloudiness. Ophthalmic examination revealed a
      CRVO in his right eye. CONCLUSION: Although COX-2 inhibitors are safe in the
      majority of patients, under certain conditions they may induce prothrombotic
      effects. Few patients with predisposed thrombosis may be at risk for
      cardiovascular and ocular thrombotic events.

PMID- 16088246
TI  - CYP4V2 mutations in two Japanese patients with Bietti's crystalline dystrophy.
AB  - Bietti's crystalline dystrophy (BCD) is an autosomal-recessive retinal dystrophy
      characterized by numerous glistening intraretinal dots scattered over the fundus,
      particularly in the posterior pole. The purpose of this study was to report
      mutations in the CYP4V2 gene (encoding a ubiquitously-expressed 525-amino acid
      sequence belonging to the CYP450 family) and to investigate the impact of the
      mutation on pre-mRNA splicing. DNA and RNA analyses were conducted using blood
      samples from two unrelated Japanese patients with BCD (a 46-year-old female and a
      52-year-old male). In the female patient, a homozygous deletion/insertion
      mutation (g.IVS6-8_-1delc.802_810del/insGC) including the 3 -acceptor splice site
      was identified. Reverse transcription-PCR analysis revealed that the complete
      length of exon 7 (186 bp), is skipped, resulting in the in-frame deletion
      mutation (p.V268_E329del). Conversely, the male patient was a compound
      heterozygote for the deletion/insertion and novel nonsense (p.W340X) mutations.
      Clinically, the female patient had decreased visual acuity, constriction of
      visual fields, severely reduced amplitudes in both rod and cone
      electroretinograms (ERGs). Despite being 6 years older, the male patient
      presented with milder clinical manifestations having good visual acuity and
      substantial amplitudes in both rod and cone ERGs. Because the CYP4V2 truncated
      protein with the p.W340X mutation lacks 186 amino acids at the C-terminus, if
      expressed, it retains 62 amino acids encoded in exon 7, which are important for
      enzymatic activity. In the male patient, expression of both mutant alleles may
      compensate for the malfunction of each mutated protein and could explain why a
      milder form of BCD results from compound heterozygosity.

PMID- 16088247
TI  - Hearing benefit of patients after Vibrant Soundbridge implantation.
AB  - The present paper compares the audiometric results of different digital Vibrant
      Soundbridge audio processors (D and Signia) of patients with mild to severe
      sensorineural hearing loss. In a retrospective study, the audiometric results
      were evaluated and compared in terms of functional gain of warble tone
      measurements and speech audiometric data. 23 patients implanted between 1998 and
      2003 with the Vibrant Soundbridge were included. At the time of implantation,
      they fulfilled the indication criteria for an implantation (7 patients with a D
      type, 16 with a Signia type while 3 patients changed from the D to the Signia
      type). The mean functional gain was increased from 22.8 dB (+/-6.5 dB SD) in the
      D type to 29.8 dB (+/-2.9) in the Signia type group. The speech-in-noise
      understanding was better in the Signia compared to the D type (59.3 +/- 11.5 dB
      and 65.7 +/- 10.1 dB, respectively). The latest upgrade of the external processor
      from the 3-channel, digital D type to the 8-channel, digital Signia type led in
      our data to an auditory benefit in all patients.

PMID- 16088248
TI  - In vivo observation of papillae of the human tongue using confocal laser scanning
      microscopy.
AB  - The aim of this investigation was to visualize the epithelial structures of the
      tongue using confocal laser scanning microscopy (LSM). The human tongue
      epithelium of 28 healthy subjects, aged 21-67 years, mean age 38 years, 14 women
      and 14 men, was examined in vivo by LSM. Using LSM, a combination of the
      Heidelberg Retina Tomograph HRT II and the Rostock Cornea Module, up to 800-fold
      magnifications were obtained. On the tongue surface both filiform and fungiform
      papillae and their taste pores were easily identified. The epithelium of the
      tongue with its subcellular structures could be observed up to a depth of 50
      microm, cellular structures up to 150 microm and subepithelial vessels up to 300
      microm. Additionally the papillary crests and blood flow were visible. Confocal
      LSM seems suitable for noninvasive in vivo examination of the tongue. The
      hydraulic z scan, the manual start setting and the measurement of the depth allow
      a clear classification of the observed structures.

PMID- 16088249
TI  - Testosterone reverses ethanol-induced deficit in spatial reference memory in
      castrated rats.
AB  - The present study was designed to evaluate the effects of ethanol, testosterone
      and combination of ethanol and testosterone, on spatial reference memory and beta
      endorphin (beta-EN) levels in castrated rats. Male Sprague-Dawley rats (120-150
      g) were used in this study, Animals were castrated and ethanol, testosterone or
      combination of the drugs were administered to rats at 09:00 h. The drugs were
      administered after a training period of 5 days and spatial reference memory was
      evaluated for 7 days using the Morris water maze. One hour after the last
      injection, animals were sacrificed, their brains removed and dissected into
      cortex, hypothalamus, hippocampus and midbrain. The beta-EN levels in these brain
      regions were determined by radioimmunoassay. The time to find the platform
      (latency period) was significantly increased in ethanol-treated rats, indicating
      that ethanol induces deficit in spatial reference memory. On the other hand,
      testosterone administration improved spatial reference memory by significantly
      decreasing the latency period. In addition, there was a significant decrease in
      latency period in the animals treated with combination of ethanol and
      testosterone. Results also indicate that administration of ethanol resulted in a
      significant increase in beta-EN levels in the hippocampus and in the cortex while
      concurrent administration with testosterone abolished this increase. These
      findings clearly indicate that administration of testosterone did not only
      improve memory but also abolished the spatial memory deficit induced by ethanol
      in castrated rats.

PMID- 16088250
TI  - Reversal of triazolam tolerance and withdrawal-induced hyperlocomotor activity
      and anxiety by bupropion in mice.
AB  - Chronic administration of triazolam (0.25 mg/kg/day, i.p.) on days 1-8 and its
      withdrawal produced an anxiogenic reaction in mice as assessed in the mirrored
      chamber test. Daily administration of bupropion (2 or 5 mg/kg, i.p.) prior to
      triazolam for 8 days prevented withdrawal-induced anxiety in mice. Triazolam
      withdrawal also induced a significant increase in the locomotor activity of mice
      indicating an anxiogenic response. Daily administration of bupropion (2 or 5
      mg/kg) prior to triazolam for 8 days also prevented withdrawal-induced increased
      locomotor activity. In conclusion, chronic administration of bupropion (2 and 5
      mg/kg) exhibited a significant protection against triazolam withdrawal-induced
      anxiety and hyperlocomotor activity in mice. The result suggests the protective
      effect of bupropion in the management of triazolam withdrawal reactions.

PMID- 16088252
TI  - Ventriculosubgaleal shunts for posthemorrhagic hydrocephalus in premature
      infants.
AB  - OBJECTIVE: The early management of posthemorrhagic hydrocephalus in premature
      infants is challenging and controversial. These infants need a temporary
      cerebrospinal fluid (CSF) diversion procedure until they gain adequate weight,
      and the blood and protein levels in CSF are reasonably low before permanent shunt
      can be placed. Various options are available with their associated advantages and
      disadvantages. Ventriculosubgaleal shunts have been recommended as a more
      physiologic and less invasive means of achieving this goal. We have performed
      this procedure in 6 premature infants to evaluate their effectiveness and
      complications. METHODS: Six consecutive premature infants with posthemorrhagic
      hydrocephalus underwent placement of ventriculosubgaleal shunts over a 1-year
      period of time. We reviewed their clinical and imaging progress to assess the
      ability of the shunt to control hydrocephalus and the complication rates.
      RESULTS: In all 6 patients, the ventriculosubgaleal shunt controlled the
      progression of hydrocephalus as assessed by clinical and imaging parameters. A
      permanent shunt was avoided in 1 patient (16.6%). However, 4 patients developed
      shunt infections, 1 involving the ventriculosubgaleal shunt itself, and 3
      immediately after conversion to ventriculoperitoneal shunt. The total infection
      rate of the series was 66.6%. All infections were caused by staphylococcus
      species. There was only a 1% shunt infection rate in our institution for all
      nonventriculosubgaleal shunts during the same period of time. CONCLUSION:
      Placement of ventriculosubgaleal shunts for interim CSF diversion in neonates
      with posthemorrhagic hydrocephalus is effective as a temporary method of CSF
      diversion. However, our experience has shown that it is associated with a
      unacceptably high CSF infection rate. A potential cause for infection is CSF
      stasis just beneath the extremely thin skin of the premature infants, promoting
      colonization by skin flora. CSF sampling before conversion to a permanent shunt
      and replacement of the proximal hardware, which has been in situ for a prolonged
      period, may decrease the infection rates. At present, the procedure is no longer
      performed at our institution.

PMID- 16088251
TI  - Incidence of childhood brain tumors in Syria (1993-2002).
AB  - OBJECTIVE: To determine whether the incidence and location of childhood CNS
      tumors in Syria follows the same pattern described in Western and Far Eastern
      countries. PATIENTS AND METHODS: We analyzed the data compiled from 367 children
      with brain tumors operated on in our Department of Neurosurgery between 1993 and
      mid-2002. We excluded all vascular and metastatic lesions and adopted the latest
      WHO classification in grouping all glial tumors. RESULTS: We found that 47% of
      brain tumors were located in the supratentorial, and 53% in the infratentorial
      region. The ratio of male to female occurrence was 1:1.2 (52% males, 48%
      females). For lesions in the supratentorial space, the distribution was 56% males
      and 44% females, while in the posterior fossa, the distribution was 61% males and
      39% females. Low-grade tumors (WHO I/II) constituted 53.5% of all lesions, and
      the rest were high grade tumors (WHO III/IV) 46.5%. The most common tumor found
      in our childhood population was medulloblastoma (27.5%), followed by astrocytoma
      (25.8%), then craniopharyngioma (14.1%). The most common tumor in the posterior
      fossa was medulloblastoma (53.5%), followed by astrocytoma (22.5%), then
      ependymoma (17%). The most common tumors in the supratentorial space were
      astrocytoma and craniopharyngioma. CONCLUSIONS: In our patient population, the
      incidence and distribution of CNS tumors were somehow different than those
      reported by authors from the Western and Far Eastern countries. Whether these
      results are unique to Syria, or reflect a regional difference in the disease
      distribution between the Middle East region and the rest of the world, remains to
      be determined.

PMID- 16088253
TI  - Long-term survival of individuals with myelomeningocele.
AB  - The objectives of this study were to extend survival analysis into adulthood for
      patients with myelomeningocele (MM) and to compare survival curves for patients
      born with varying defect severity before and after 1975. We have reviewed
      existing data for 904 patients with MM seen in a large multidisciplinary
      children's clinic over 43 years. Before 1975, a major contributor to decreased
      survival is death during infancy. The presence of cerebral spinal fluid shunting
      is a major contributor to increased survival. After 1975, survival to adolescence
      is similar regardless of shunt status (p = 0.17). For all patients alive at age
      16, a significant decrease in survival probability after age 34 years was found
      for individuals with shunted hydrocephalus compared to those without a shunt (p =
      0.03). Although childhood survival for individuals born after 1975 is not related
      to shunt status, adults with MM and shunted hydrocephalus may be at risk for
      decreased longevity.

PMID- 16088254
TI  - Magnetic resonance imaging of primary orbital Ewing's sarcoma.
AB  - The authors describe the MRI findings of a primary orbital Ewing's sarcoma in a 5
      year-old boy, who underwent an extensive tumour surgery as these findings were
      mistaken for more chemoresistant sarcomas such as rhabdomyosarcoma. This case
      illustrates the fact that MR findings of primary orbital Ewing's sarcoma may be
      different from those of Ewing's sarcoma present elsewhere in the body. An
      accurate preoperative diagnosis may therefore result in a more conservative
      approach and prove extremely useful in such tumours.

PMID- 16088255
TI  - Adenoid-tonsillectomy to treat visual dysfunction in a child with
      craniosynostosis.
AB  - We report a child with isolated saggital synostosis where a gradual deterioration
      of the P100 component of the pattern reversal visual evoked potential recorded
      during the day was associated with episodes of upper airway obstruction during
      sleep that correlated with periods of ICP spiking. Adenoid-tonsillectomy reversed
      this deterioration with coincident increase in SaO2 and decreased sleep apnoea.

PMID- 16088256
TI  - Paradoxical intracranial tuberculoma requiring surgical treatment.
AB  - Paradoxical enlargement of intracranial tuberculomas or development of new ones
      during adequate antituberculous chemotherapy is an uncommon event. Treatment of
      such cases is controversial. Steroid therapy is usually advocated without change
      in the antituberculous drug program. However, in some patients whose lesions fail
      medical treatment, or who have superficially located large lesions, surgical
      therapy may be required. A 15-year-old girl with pulmonary miliary tuberculosis,
      tuberculous meningitis and multiple intracranial tuberculomas is presented. While
      her pulmonary lesions and intracranial tuberculomas except one were healed with
      chemotherapy, one tuberculoma increased in size 1 month after starting
      chemotherapy. She was followed with dexamethasone treatment in addition to
      antituberculous therapy for 2 months. Then, the lesion was removed because it had
      increased in size in spite of appropriate chemotherapy.

PMID- 16088257
TI  - Supratentorial arterial ischemic stroke following cerebellar tumor resection in
      two children.
AB  - We describe two children who developed ischemic strokes in the territory of the
      middle cerebral artery, one 7 days and one 11 days after resection of a
      cerebellar tumor. In the first child, another infarction occurred in the
      territory of the contralateral middle cerebral artery 5 days after the first
      stroke. No specific cause or underlying risk factor other than the surgical
      procedure was found. The subacute clinical course at stroke onset resembled that
      of the 'posterior fossa syndrome', suggesting a common underlying mechanism.

PMID- 16088258
TI  - Pseudotumor cerebri: disordered cerebrospinal fluid hydrodynamics with extra
      axial CSF collections.
AB  - Pseudotumor cerebri is uncommon in the pediatric age group and presents with
      clinical characteristics different from the adult form. We report a 5-year-old
      boy who presented with--seemingly spontaneous--alternating subdural CSF
      collections before progressing to develop pseudotumor cerebri. To our knowledge,
      this is the first report of such a presentation. In the prepubertal pediatric age
      group, pseudotumor cerebri may be associated with multiple etiologic factors
      (more than in the adult population). The exact common mechanism behind such a
      disorder is not known. Pseudotumor cerebri may be a disorder of CSF
      hydrodynamics. It may also be linked to other disorders of CSF hydrodynamics, as
      in our case. The exact link and mechanistic differences between these apparently
      related disorders deserve further analysis and investigation, possibly through
      dynamic MRI techniques.

PMID- 16088259
TI  - Spinal ganglioneuroma mimicking adolescent idiopathic scoliosis.
AB  - The authors report a 12-year-old girl who presented with a 2-year progressive
      painless thoracic scoliosis. Her previous development had been normal with no
      significant past history of illness. MRI revealed a thoracic ganglioneuroma,
      which was confirmed by surgical pathology. Ganglioneuroma might cause progressive
      spinal deformity mimicking adolescent idiopathic scoliosis. A careful
      preoperative survey is mandatory for patients diagnosed with scoliosis with a
      rigid or rapidly progressive curve. The authors recommend a combination of
      neurosurgery and orthopedic spine surgery to treat this condition.

PMID- 16088260
TI  - Cerebellopontine angle arachnoid cyst harbouring ectopic neuroglia.
AB  - Arachnoid cysts are collections of cerebrospinal fluid covered by arachnoidal
      cells and collagen. They may have a congenital or acquired origin. We present the
      case of a 7-year-old boy with a cerebellopontine angle arachnoid cyst harbouring
      a portion of neuroglia. Microscopically, the cyst wall consisted of a delicate
      fibrovascular membrane lined by a layer of arachnoidal cells. A thin layer of
      glial tissue ran the whole length of the cyst wall. This finding supports a
      congenital origin for this case. Cerebellopontine angle arachnoid cysts
      harbouring neuroglia without ependymal elements are very rare lesions and may be
      successfully treated by surgical resection.

PMID- 16088261
TI  - Posterior fossa tumor presenting as a giant macrocranium in an infant.

PMID- 16088262
TI  - Fatal penetrating brainstem injury caused by bicycle brake handle.

PMID- 16088263
TI  - Universals of human nature.

PMID- 16088264
TI  - A randomized controlled trial of Japanese patients with obsessive-compulsive
      disorder--effectiveness of behavior therapy and fluvoxamine.
AB  - BACKGROUND: The aim of this study was to confirm and compare the efficacy of
      fluvoxamine (the only licensed SSRI for treatment for OCD in Japan) and behavior
      therapy in treating Japanese patients with OCD. In addition, we investigated
      predictors of these treatments. METHODS: Thirty-one outpatients meeting the DSM
      III-R criteria for OCD without any axis I disorder were randomly assigned to one
      of three treatment conditions: BT (behavior therapy +/- pill placebo), FLV
      [autogenic training (a psychological placebo for OCD) +/- fluvoxamine] and
      control group [autogenic training (psychological placebo) +/- pill placebo] for
      12 weeks of treatment. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the
      Clinical Global Impression-Improvement Scale (CGI-I) were administered blindly at
      baseline and week 4, 8 and 12. RESULTS: Twenty-eight patients completed this
      study. Patients in the BT and FLV groups showed significantly more improvement
      than those in the control group in the mean score of total Y-BOCS; moreover, the
      BT group showed significantly more reduction in total Y-BOCS score at the end of
      treatment than the FLV group (BT > FLV, p < 0.01). Patients with lower baseline
      total Y-BOCS, past history of a major depressive episode and absence of cleaning
      compulsion improved more with fluvoxamine. CONCLUSIONS: We confirmed the
      effectiveness of behavior therapy and fluvoxamine for Japanese patients with OCD.
      Behavior therapy improved the condition of OCD patients more than fluvoxamine.

PMID- 16088265
TI  - Effects of mind-body therapy on quality of life and neuroendocrine and cellular
      immune functions in patients with ulcerative colitis.
AB  - BACKGROUND: The aim of this study was to investigate the effects of mind-body
      therapy on neuroendocrine and cellular immune measures, health-related quality of
      life and disease activity in patients with ulcerative colitis (UC) in remission.
      METHODS: Thirty UC patients in remission or with low disease activity were
      randomly assigned to an intervention group (n = 15) or a usual-care waiting
      control group (n = 15). Intervention consisted of a structured 60-hour training
      program over 10 weeks which included stress management training, moderate
      exercise, Mediterranean diet, behavioral techniques and self-care strategies.
      Quality of life, perceived stress and disease activity were assessed with
      standardized questionnaires (IBDQ, SF-36, PSS, CAI). In addition, the
      distribution of circulating lymphocytes and lymphocyte subsets as well as the
      beta-adrenergic modulation of TNF-alpha production in vitro were analyzed. Urine
      catecholamines and plasma cortisol, prolactin and growth hormone were measured
      pre- and postinterventionally, and were compared with a healthy control group (n
      = 10). RESULTS: In response to therapy, patients in the intervention group showed
      significantly greater improvement in the SF-36 scale Mental Health and the
      Psychological Health Sum score compared with changes observed in the usual-care
      waiting control group. Patients in the intervention group showed significantly
      greater improvement on the IBDQ scale Bowel Symptoms compared with the control
      group. However, no significant group differences in circulating lymphocyte
      subsets or endocrine parameters were observed in response to therapy. In
      addition, no significant effects of intervention on either the basal levels of
      TNF-alpha or the suppressive action of the beta-adrenergic agonist isoproterenol
      on TNF-alpha production were observed. CONCLUSION: Mind-body therapy may improve
      quality of life in patients with UC in remission, while no effects of therapy on
      clinical or physiological parameters were found, which may at least in part be
      related to selective patient recruitment.

PMID- 16088266
TI  - The effects of repeated thermal therapy for patients with chronic pain.
AB  - BACKGROUND: It has been reported that local thermal therapy with a hot pack or
      paraffin relieves pain. We hypothesized that systemic warming may decrease pain
      and improve the outcomes in patients with chronic pain. The purpose of this study
      was to clarify the effects of systemic thermal therapy in patients with chronic
      pain. METHODS: Group A (n = 24) patients with chronic pain were treated by a
      multidisciplinary treatment including cognitive behavioral therapy,
      rehabilitation, and exercise therapy, whereas group B (n = 22) patients were
      treated by a combination of multidisciplinary treatment and repeated thermal
      therapy. A far-infrared ray dry sauna therapy and post-sauna warming were
      performed once a day for 4 weeks during hospitalization. We investigated the
      improvements in subjective symptoms, the number of pain behavior after treatment
      and outcomes 2 years after discharge. RESULTS: The visual analog pain score,
      number of pain behavior, self-rating depression scale, and anger score
      significantly decreased after treatment in both groups. After treatment, the
      number of pain behavior was slightly smaller (p = 0.07) and anger score was
      significantly lower in group B than those in group A (p = 0.05). Two years after
      treatment, 17 patients (77%) in group B returned to work compared with 12
      patients (50%) in group A (p < 0.05). CONCLUSION: These results suggest that a
      combination of multidisciplinary treatment and repeated thermal therapy may be a
      promising method for treatment of chronic pain.

PMID- 16088267
TI  - Do cognitive complaints in euthymic bipolar patients reflect objective cognitive
      impairment?
AB  - BACKGROUND: In clinical practice, bipolar patients complain of cognitive deficits
      such as attentional or memory disturbances. The main aim of this study was to
      determine whether subjective cognitive complaints were associated with objective
      neuropsychological impairments. METHOD: Sixty euthymic bipolar patients were
      assessed through a neuropsychological battery. A structured clinical interview
      was used to determine subjective cognitive complaints in patients. Thirty healthy
      controls were also included in the study in order to compare the
      neuropsychological performance among groups. RESULTS: Bipolar patients with a
      higher number of episodes, especially the number of mixed episodes, longer
      duration of the illness and the onset of the illness at an earlier age showed
      more subjective complaints. Furthermore, bipolar patients with subjective
      complaints showed lower scores in several cognitive measures related to
      attention, memory and executive function compared with the control group.
      Nevertheless, patients without complaints also performed less well than controls
      in some neuropsychological measures. CONCLUSION: Bipolar patients who were aware
      of cognitive deficits were more chronic, had presented more previous episodes,
      especially mixed type, and their illness had started at an earlier age compared
      with patients who did not complain about cognitive problems. Moreover, patients
      with good cognitive insight also had a poorer social and occupational functioning
      as well as a poorer neuropsychological performance. However, the bipolar group
      without complaints also obtained lower scores in several tests compared with
      healthy controls. Cognitive status of bipolar patients should be routinely
      assessed, regardless of the patients awareness about their cognitive deficits.

PMID- 16088268
TI  - Anger attacks in depression--evidence for a male depressive syndrome.
AB  - BACKGROUND: It has been proposed that aggression and especially anger attacks
      play an important role in the symptomatology of depression. Furthermore, it has
      been hypothesized that these symptoms are more prevalent in males than in
      females. METHODS: We conducted a study in 217 depressed patients (104 females,
      113 males) without psychiatric comorbidity using questionnaires. Study subjects
      had previously been treated as inpatients and were contacted after discharge from
      hospital by mail or phone. Overall response rate was 69.6%. Patients were asked
      to retrospectively rate their state during their last depression. RESULTS: Males
      obtained higher scores on irritability (p = 0.010) and showed a tendency to
      overreact (p = 0.018) during their last depressive episode. They had suffered
      significantly more often from anger attacks than female patients (4.3 +/- 7.52
      versus 1.2 +/- 2.97 anger attacks per month; p = 0.001). Further multivariate
      analyses displayed that men had significantly lower impulse control and more
      frequently showed symptomatic substance intake and hyperactive behavior during
      their depression, whereas women suffered more often from hypersomnia and
      heaviness in limbs (p < 0.0001). CONCLUSION: Our findings are indicative of
      gender differences in symptoms related to lowered impulse control in depressed
      patients. Further study is required to replicate and extend our results and to
      assess the significance of aggression as a gender-specific diagnostic criterion
      for depression.

PMID- 16088269
TI  - Psychogenic urinary retention ('paruresis'): diagnosis and epidemiology in a
      representative male sample.
AB  - BACKGROUND: Although research interest in social phobias has expanded during the
      last decade, a special subtype of social phobia known as paruresis, which
      manifests in the inability to urinate in public rest rooms, is rarely mentioned.
      The aim of the present study was to achieve for the first time an estimation of
      point prevalence in a representative male sample (n = 1,105). METHOD: Due to the
      lack of well-established screening instruments for paruresis, the Paruresis
      Checklist (PCL) must be tested for reliability and validity. An empirically based
      cutoff score must be determined by using the subjective interference with
      everyday life as an external criterion. RESULTS: Reliability of the PCL seemed to
      be sufficient, and adequate evidence for validity was found. Using the
      empirically based cutoff score of the PCL, 2.8% of the sample was diagnosed as
      suffering from paruresis. In contrast to other forms of social phobia, paruresis
      is not associated with a lower educational or occupational level.

PMID- 16088270
TI  - Psychosomatic assessment of skin diseases in clinical practice.
AB  - BACKGROUND: Psychiatric disorders are frequent in dermatology patients, and many
      studies pointed out complex, mutual relationships between psyche and skin. Our
      aim was to provide a systematic psychosocial evaluation of a large and
      heterogeneous population of patients with skin diseases, including assessments of
      quality of life, psychiatric status according to the DSM-IV and psychological
      conditions with psychosomatic relevance according to established criteria
      (Diagnostic Criteria for Psychosomatic Research, DCPR). METHODS: We studied 545
      dermatological inpatients aged 18-65 years, free from dementia and cognitive
      impairment. They completed the Skindex-29 and the 12-item General Health
      Questionnaire (GHQ-12) and were administered the SCID-I and the Structured
      Interview for Psychological Conditions of Psychosomatic Relevance by a trained
      mental health professional blinded to questionnaire scores. RESULTS: Overall, 38%
      of patients received a DSM-IV diagnosis. The most common diagnoses were mood
      (20%) and anxiety disorders (16%); 48% of patients also received a DCPR
      diagnosis. The most common were demoralisation, irritable mood, type A behaviour
      and various forms of abnormal illness behaviour. Adjusting for gender, age, and
      education, the presence of DSM-IV or DCPR diagnoses was significantly associated
      with high scores on the GHQ-12 and on the Functioning and Emotions scales of the
      Skindex-29. Also, DCPR diagnoses were significantly associated with high scores
      on the Symptoms scale of the Skindex-29. CONCLUSIONS: These findings highlight
      the high frequency of psychosocial problems in patients with skin disease and
      suggest that the joint use of DSM-IV and DCPR criteria may help identify those
      patients in whom psychiatric issues are worthy of increased clinical attention.

PMID- 16088271
TI  - Prodromal symptoms in myocardial infarction.
AB  - BACKGROUND: Little is known about the prodromal phase of myocardial infarction
      (MI). The aim of this study was to explore this phase with methodologies which
      have been standardized in affective disorders. The psychological evaluation of
      patients with MI diagnosis is currently based on DSM-IV criteria. An alternative
      diagnostic and conceptual framework has been proposed by an international group
      of psychosomatic investigators. In this study, we are going to compare these new
      criteria, i.e. the Diagnostic Criteria for Psychosomatic Research (DCPR), with
      DSM-IV in a population where a high prevalence of psychological problems is
      expected. METHODS: A semistructured research interview based on Paykel's Clinical
      Interview for Depression for eliciting prodromal symptoms was administered to a
      consecutive series of 92 patients with a first episode MI diagnosis. Two
      interviews for the evaluation of psychological problems were administered
      according to DSM-IV and DCPR criteria. RESULTS: Most of the patients reported
      prodromal symptoms. Irritability, depressed mood and somatic anxiety were the
      most common prodromal symptoms. The results also show that the number of DCPR
      diagnoses was higher than the number of DSM-IV diagnoses. At least one DCPR
      diagnosis was found in all patients, whereas at least one DSM-IV diagnosis was
      present in 42 (46%) patients. CONCLUSIONS: The prodromal phase of MI was found to
      be characterized by prodromal symptoms of affective type. The joint use of DSM-IV
      and DCPR criteria was found to improve the identification of psychological
      factors which could affect this phase. The results should alert the physician to
      the fact that patients presenting with irritability, depressed mood (including
      demoralization), anxiety and insomnia may be at risk of developing coronary
      artery disease.

PMID- 16088272
TI  - Stopping bacterial adhesion: a novel approach to treating infections.
AB  - Adhesion and colonization are prerequisites for the establishment of bacterial
      pathogenesis. The prevention of adhesion is an attractive target for the
      development of new therapies in the prevention of infection. Bacteria have
      developed a multiplicity of adhesion mechanisms commonly targeting surface
      carbohydrate structures, but our ability to rationally design effective
      antiadhesives is critically affected by the limitations of our knowledge of the
      human 'glycome' and of the bacterial function in relation to it. The potential
      for the future development of carbohydrate-based antiadhesives has been
      demonstrated by a significant number of in vitro and in vivo studies. Such
      therapies will be particularly relevant for infections of mucosal surfaces where
      topical application or delivery is possible.

PMID- 16088273
TI  - Pleural fluid pH in parapneumonic pleural effusions: drawing the line.

PMID- 16088274
TI  - Tuberculosis: an ancient disease still confusing our genes.

PMID- 16088275
TI  - Obesity and sleep: beyond yin and yang.

PMID- 16088276
TI  - Multilevel and continuous pleural fluid pH likelihood ratios for draining
      parapneumonic effusions.
AB  - BACKGROUND: Although clinical practice guidelines endorse the use of pleural
      fluid pH to select patients with parapneumonic effusions for pleural drainage, no
      studies have reported likelihood ratios for pleural fluid pH. OBJECTIVES: We
      derived and tested the value of continuous likelihood ratios for selecting
      pneumonia patients for pleural drainage. METHODS: Patient level pleural fluid pH
      results were obtained from a registry of primary studies that assessed the
      discriminative properties of pH. Multilevel likelihood ratios were calculated for
      four pH intervals. Continuous likelihood ratios were derived from logistic
      regression using discrete pH values. Binary, multilevel and continuous likelihood
      ratios were compared to evaluate the statistical (chi2) and clinical advantages
      of continuous likelihood ratios. RESULTS: Hundred and ninety-seven pleural fluid
      pH results were retrieved from published reports and categorized into four pH
      ordinal intervals. Multilevel likelihood ratios ranged from a low of 0.13 (95%
      CI, 0.04-0.41) for pH values >7.40 to a high of 15.80 (95% CI, 7.04-35.45) for pH
      values < or =7.00. Logistic regression derived the following equation for
      continuous likelihood ratios: exp[-7.168(measured pH - 7.207)]. Continuous
      likelihood ratios offered more diagnostic information both statistically (p <
      0.005) and clinically compared with binary and multilevel likelihood ratios.
      CONCLUSIONS: Analysis of a patient registry allows the derivation of an
      exponential equation that calculates continuous likelihood ratios for discrete
      pleural fluid pH values. Continuous likelihood ratios provide more clinically and
      statistically significant information compared with binary and multilevel
      likelihood ratios for calculating posttest probabilities of the need to drain
      parapneumonic effusions.

PMID- 16088277
TI  - Pleural fluid parameters identifying complicated parapneumonic effusions.
AB  - BACKGROUND: Controversy exists regarding the clinical utility of pleural fluid
      parameters as prognosticators of complicated parapneumonic effusions that require
      drainage. OBJECTIVES: The purpose of this prospective study is to further assess
      the utility of these parameters in the management of a larger series of
      parapneumonic effusions and to determine appropriate binary decision thresholds.
      METHODS: We studied 238 consecutive patients with parapneumonic effusions who
      underwent diagnostic thoracentesis. RESULTS: We found that pleural fluid pH had
      the highest diagnostic accuracy (area under the curve, AUC: 0.928; 95% confidence
      interval, CI: 0.894-0.963) compared with pleural fluid glucose (AUC: 0.835; 95%
      CI: 0.773-0.897), LDH (AUC: 0.824; 95% CI: 0.761-0.887) or pleural fluid volume
      (AUC: 0.706; 95% CI: 0.634-0.777). The optimal binary decision threshold for
      pleural fluid pH identifying complicated effusions requiring drainage was 7.15.
      Binary, multilevel and continuous likelihood ratios (LRs) for pH were calculated
      to estimate the likelihood of complication of the pleural effusion. Values for
      the LRs were compared for each of the three strategies, and relative clinical and
      statistical significances were assessed. Binary LRs provided significantly less
      information than continuous strategies. CONCLUSION: The pH has the highest
      diagnostic accuracy for identifying complicated parapneumonic pleural effusions.
      The binary decision threshold determining the need for chest drainage is 7.15 in
      our patient series. We recommend continuous LRs to estimate the post-test
      probability of the complication as they provide the most information compared
      with binary LRs. Our results do not support the use of pleural fluid LDH as
      independent predictor of complicated parapneumonic effusions.

PMID- 16088278
TI  - Lack of an association between interleukin-12 receptor beta1 polymorphisms and
      tuberculosis in Koreans.
AB  - BACKGROUND: The fact that only 10% of people infected with Mycobacterium
      tuberculosis develop clinical tuberculosis (TB) suggests the presence of genetic
      factors in the pathogenesis of TB. To date, a number of single nucleotide
      polymorphisms (SNPs) in several candidate genes have been proposed as genetic
      risk factors of TB; however, reports are conflicting. OBJECTIVES: We investigated
      whether SNPs in the interleukin (IL)-12 receptor beta1 gene are associated with
      TB in Koreans. METHODS: One hundred and fifteen patients with bacteriologically
      or pathologically confirmed TB and 151 healthy anonymous blood donors were
      enrolled. The genotypes of 5 SNPs on IL-12 receptor beta1 gene, +705A/G (Q214R),
      +1158T/C (M365T), +1196G/C (G378R), +1637G/A (A525T) and +1664 C/T (P534S), were
      determined by PCR-RFLP. RESULTS: No difference was observed between TB patients
      and controls in terms of the genotype frequencies of the 5 SNPs of the IL-12
      receptor beta1 gene or of their haplotypes. CONCLUSIONS: In view of the finding
      that these SNPs have been reported to be associated with TB in the Japanese and
      Moroccan populations, our results may reflect racial differences in genetic
      susceptibility to TB.

PMID- 16088279
TI  - Response to empirical anti-tuberculosis treatment in patients with sputum smear
      negative presumptive pulmonary tuberculosis.
AB  - BACKGROUND: In many cases, physicians initiate anti-tuberculosis (TB) treatment
      based only on symptoms or radiographic findings without confirmation of pulmonary
      TB by acid-fast bacilli (AFB) smear. It has not been well known which clinical
      characteristics could be used as predictors for positive culture or real TB in
      patients with sputum smear-negative presumptive pulmonary TB. OBJECTIVE: We tried
      to elucidate treatment outcomes in patients with sputum smear-negative
      presumptive pulmonary TB and to find predictors of positive culture results.
      METHODS: We reviewed data of the patients who had been treated as presumptive TB
      with negative AFB smear on the basis of clinical and radiographic features from
      December 1998 to December 2000 at a university hospital in Korea. We reviewed
      medical records and radiographs of patients and analyzed possible predictors for
      positive culture. RESULTS: One hundred and one patients were enrolled. Among
      them, pulmonary TB was confirmed by culture in 32 patients (31%). Thirty-one
      (96.9%) out of 32 culture-positive patients showed clinical or radiographic
      improvement as did 50 (72.5%) out of 69 culture-negative patients. The predictor
      for a positive culture result is the presence of patchy consolidation in an
      initial radiograph (p = 0.025; OR 2.89; 95% CI 1.14-7.28). CONCLUSIONS: The
      empirical anti-TB treatment in patients with sputum smear-negative presumptive
      pulmonary TB was effective and adequate, especially presented with patchy
      consolidation in initial chest radiographs in Korea.

PMID- 16088280
TI  - Psychotherapy improves compliance with tuberculosis treatment.
AB  - BACKGROUND: Low treatment completion rate in tuberculosis (TB) patients is a
      major concern. Physicians have always been striving for better treatment
      adherence in such patients. The present study is one such attempt in this
      direction. OBJECTIVES: The study was aimed to evaluate the role of behavior
      modification by psychotherapy in improving compliance with short-course anti-TB
      chemotherapy in India. METHODS: It was a prospective controlled trial involving
      patients with confirmed pulmonary and extrapulmonary TB enrolled in the National
      Tuberculosis Program. The intervention group underwent pretreatment psychological
      assessment followed by regular psychotherapy sessions. RESULTS: The intervention
      group had a demographic profile comparable to that of the control group. The
      patients were mostly from low- and middle-income backgrounds from urban and semi
      urban areas. They consistently showed poor knowledge about the nature of the
      disease, low motivation, and had considerable apprehensions. Following the
      sessions, the intervention group showed improved compliance compared with the
      control group, reflected in significantly higher treatment completion and cure
      rates. CONCLUSIONS: The study suggests that psychological intervention is
      effective in improving compliance with anti-TB treatment, and may reduce the
      incidence of treatment failure, relapse and drug resistance.

PMID- 16088281
TI  - Total antioxidant status and severity of community-acquired pneumonia: are they
      correlated?
AB  - BACKGROUND: Oxidant/antioxidant imbalance has been reported in various
      respiratory diseases including pneumonia. However, the role of blood antioxidants
      has not been fully discussed. OBJECTIVES: The aim of this exploratory study was
      to assess serum total antioxidant status (TAS) in patients with community
      acquired pneumonia (CAP) and the probable correlation with the severity of the
      disease. METHODS: Thirty patients (22 men, 8 women; mean age of 48 +/- 21 years)
      and 10 healthy nonsmokers (mean age 44 +/- 16 years) were studied. Clinical,
      laboratory and radiological findings were recorded on the day of admission and on
      the 7th day. A severity score was calculated using the Fine scale. Serum TAS was
      measured at the same time points using a colorimetric method. RESULTS: On
      admission, TAS (TAS1) was significantly lower than on the 7th day (TAS2) (0.84 +/
      0.13 mmo/l vs. 1.00 +/- 0.17 mmo/l; p = 0.0001) and compared with the healthy
      subjects (0.84 +/- 0.13 vs. 1.19 +/- 0.09 mmol/l; p < 0.001). TAS change (TAS2 -
      TAS1) was statistically significantly more marked in smokers (0.17 vs. 0.28, p =
      0.001), in patients with factors predisposing to CAP (0.12 vs. 0.37; p = 0.000)
      and in patients with gram-negative pneumonia (0.16 vs. 0.35; p = 0.000). On the
      other hand, change in TAS was statistically significantly less marked in patients
      with lobar pneumonia (0.27 vs. 0.17; p = 0.001). Additionally, TAS change was
      positively correlated to white blood count on admission (r = 0.39; p = 0.029).
      CONCLUSIONS: It is concluded that serum TAS is decreased in patients with CAP,
      suggesting the presence of oxidative stress, and that change in TAS seems to be
      influenced by disease severity. TAS measurement may be useful in estimating the
      severity of CAP and is a probable indication for the administration of
      antioxidants in the management of the disease.

PMID- 16088282
TI  - Survival analyses of patients with thoracic complications secondary to bronchial
      carcinoma at the time of diagnosis.
AB  - BACKGROUND: The impact on survival of thoracic complications secondary to
      bronchial carcinoma has not been clearly analyzed. OBJECTIVES: The purpose of
      this study was to assess the significance of these complications for the survival
      of lung cancer patients. METHODS: All patients diagnosed at our center from March
      2000 to January 2004 were analyzed to estimate survival among patients with or
      without thoracic complication. Any intrathoracic change or abnormality secondary
      to bronchial carcinoma such as atelectasis or pleural effusion was defined a
      thoracic complication. Survival was calculated using the Kaplan-Meier method, and
      the complications predicting survival were evaluated using Cox's regression
      analysis. RESULTS: Of the 182 eligible patients, 61.5% had at least one thoracic
      complication. The complications were atelectasis, pulmonary metastases, pleural
      effusion, laryngeal nerve involvement, vena cava superior syndrome and others.
      Specific survival times for each complication were not different, except in the
      case of atelectasis. Median survival was significantly longer in patients with
      atelectasis, as opposed to nonatelectatic patients. Survival times in patients
      with at least one complication were not different than those of patients without
      complication. However, median survival of patients with one of the complications,
      excluding atelectasis (since this was associated with improved survival), was 3
      months shorter (p = 0.029). Cox's regression analysis also predicted atelectasis
      for improved survival. CONCLUSION: Atelectasis, which was determined to be the
      most frequent thoracic complication, was identified as a favorable prognostic
      factor in patients with advanced stage lung cancer.

PMID- 16088283
TI  - Leptin and ghrelin levels in patients with obstructive sleep apnea syndrome.
AB  - BACKGROUND: Leptin is a hormone with well-investigated functions concerning body
      composition, energy homeostasis and feeding behavior in humans. The obstructive
      sleep apnea syndrome (OSAS) is strongly associated with obesity, which is known
      to be closely associated with hyperleptinemia. More recently, ghrelin, a hormone
      that also influences appetite and energy homeostasis, has been discovered.
      OBJECTIVES: The aim of this study was to investigate serum leptin and ghrelin
      levels in obese patients with OSAS in comparison with equally obese controls
      without OSAS. METHODS: Thirty untreated obese patients with moderate-severe OSAS
      (apnea-hypopnea index: AHI > or =15) and 22 obese controls (AHI <5) were studied.
      To confirm the diagnosis, all patients underwent standard polysomnography in our
      sleep disorders center. Serum samples were taken at 08:00 h in the morning after
      overnight fasting. RESULTS: Significantly higher serum leptin levels were found
      in OSAS patients compared to controls (p = 0.012), but there was no significant
      difference in serum ghrelin levels between OSAS patients and controls. Serum
      leptin levels were significantly correlated with body mass index in both OSAS
      patients (r = 0.55, p = 0.002) and controls (r = 0.46, p = 0.028), but only in
      OSAS patients was the leptin level significantly correlated with AHI (r = 0.38, p
      = 0.036). CONCLUSION: These data support findings suggesting that leptin is a
      hormonal factor affected by OSAS and not determined by obesity alone. Further
      studies are needed to investigate the relationship between serum ghrelin and
      OSAS.

PMID- 16088284
TI  - The role of routine culture for tuberculosis during bronchoscopy examination of
      lung masses.
AB  - BACKGROUND: Many centers routinely culture bronchoscopy samples for mycobacteria
      even when tuberculosis (TB) is not strongly suspected. The value of this practice
      has hardly been investigated. OBJECTIVE: The aim of this retrospective study was
      to assess the utility of routine culture of bronchoscopy samples of lung masses
      for mycobacteria in a region where TB is not endemic. PATIENTS AND METHODS: The
      study group consisted of 168 patients who underwent bronchoscopy for
      investigation of lung masses in a major tertiary-care, university-affiliated
      facility in central Israel. The findings on acid-fast bacillus staining and
      culture were reviewed, and data on demographic characteristics were collected
      from the files. RESULTS: There were 97 men (58%) and 71 women with a mean age of
      62 +/- 25 years. One culture (0.6%) grew Mycobacterium tuberculosis. There were
      no cases of positive acid-fast bacillus smear or positive nontuberculous
      mycobacteria culture. Sixty USD (5.45%) would be saved per patient without
      clinical suspicion of TB. CONCLUSIONS: These findings highlight the need to
      formulate new guidelines for the performance of mycobacterial cultures of
      bronchoscopy specimens in areas with a low prevalence of TB.

PMID- 16088285
TI  - Respiratory impedance following bronchoscopic or surgical lung volume reduction
      for emphysema.
AB  - BACKGROUND: Bronchoscopic methods for achieving lung volume reduction (BLVR) are
      presently undergoing clinical trials, and will soon be clinically available.
      Understanding the differential effects of surgical volume reduction therapy
      (LVRS) and BLVR on lung and chest wall physiology will assist physicians in
      selecting an optimal approach for patients. OBJECTIVES: Determine whether LVRS
      adversely affects lung or chest wall physiology at 3-month follow-up relative to
      BLVR in an experimental model of sheep emphysema. METHODS: Twelve mixed-breed
      sheep were treated with papain to produce experimental emphysema, and were
      divided into control, LVRS, and BLVR treatment groups. Lung and chest wall
      impedance was measured at 0, 5, and 10 cm H2O positive end-expiratory pressure at
      baseline and 3-month follow-up. RESULTS: Emphysema was associated with increased
      airway resistance, decreased lung tissue resistance and elastance, and increased
      chest wall tissue resistance. Following treatment, equivalent increases in lung
      elastance occurred in the LVRS and BLVR groups compared to controls. LVRS did not
      adversely affect chest wall impedance despite causing extensive pleural scarring.
      CONCLUSIONS: (1) Experimental emphysema following prolonged papain exposure
      progresses after cessation of treatment. (2) BLVR and LVRS produced equivalent
      lung and chest wall impedance responses at 3-month follow-up. (3) LVRS did not
      adversely affect chest wall impedance despite being associated with extensive
      pleural scarring.

PMID- 16088286
TI  - Multiple cystic pulmonary metastases from osteosarcoma.

PMID- 16088287
TI  - Long-term inhaled nitric oxide plus dipyridamole for pulmonary arterial
      hypertension.
AB  - Inhaled nitric oxide (iNO) has been shown to be a potent and selective
      vasodilator in pulmonary arterial hypertension (PAH). However, the clinical
      experience in prolonged treatment is limited. We assess the safety and
      effectiveness of long-term administration of iNO in severe PAH. Two female
      patients were admitted to our hospital because of severe dyspnea (World Health
      Organization functional class IV) and hypoxemia. They were diagnosed with PAH
      (primary and secondary to congenital heart disease) and treated with iNO for 2
      years. The delivery system consisted of an NO tank of 800 ppm, a modified gas
      pulsing device, and nasal cannulas. On iNO treatment the patients showed
      remarkable improvement of symptoms, oxygenation and 6-min walk distance. After 16
      months the patients began to experience a progressive rebound of symptoms. A
      phosphodiesterase type 5 inhibitor (dipyridamole) was added to iNO. This
      intervention proved useful in improving clinical deterioration and hemodynamics.
      This is the first study reporting 2-year iNO therapy in 2 patients with primary
      and secondary pulmonary hypertension. The combination of dipyridamole with iNO
      augments the pulmonary vasodilatation and may be useful in managing PAH.

PMID- 16088288
TI  - Imidapril-induced eosinophilic pleurisy. Case report and review of the
      literature.
AB  - We describe an unusual case of a patient with eosinophilic pleurisy associated
      with long-term administration of imidapril, an angiotensin-converting enzyme
      inhibitor (ACEI). An 81-year-old woman who had been given imidapril for the
      treatment of essential hypertension was admitted to our hospital for
      investigation of persistent low-grade fever, dry cough and difficulty in
      breathing. Left-sided eosinophilic pleurisy was diagnosed based on eosinophilic
      pleural effusion and peripheral eosinophilia. Soon after administration of
      imidapril was discontinued, her clinical symptoms subsided, and there was
      improvement in both diagnostic imaging and laboratory findings. So far, to our
      knowledge, this is the first reported case in which ACEI induced eosinophilic
      pleurisy.

PMID- 16088289
TI  - A middle-aged woman with recurrent respiratory infections.

PMID- 16088290
TI  - Review of epidemiological studies on the occupational risk of tuberculosis in low
      incidence areas.
AB  - This review summarizes the epidemiological evidence for occupationally acquired
      tuberculosis and considers the implications for the prevention of tuberculosis.
      The relevant epidemiological studies were identified on the basis of the Medline
      data bank, starting with the year 1966. The evaluation of occupational groups
      with an elevated tuberculosis risk is exclusively based on epidemiologic studies
      of good or acceptable quality, applying clearly defined criteria of
      methodological quality. In summary, the available epidemiological evidence
      suggests that the risk of tuberculosis is elevated in the following occupational
      groups: hospital employees in wards with tuberculosis patients; nurses in
      hospitals; nurses attending HIV-positive or drug-addicted patients; pathology and
      laboratory workers; respiratory therapists and physiotherapists; physicians in
      internal medicine, anaesthesia, surgery and psychiatry; non-medical hospital
      personnel in housekeeping and transport work; funeral home employees, and prison
      employees. However, the epidemiological evidence is limited for all these
      occupations, with the exception of the nurses, because of the lack of
      methodologically adequate studies that have got the statistical power to
      differentiate between specific work tasks. There is a need for large population
      based studies with precise definition of exposure, which should include molecular
      epidemiologic methods in the investigation of occupational risk factors of
      tuberculosis.

PMID- 16088291
TI  - Neurophysiological evaluation of the optimum target in gamma thalamotomy:
      indirect evidence.
AB  - Gamma thalamotomy has been useful for the treatment of Parkinson's disease and
      other movement disorders, but it has disadvantages, such as a delayed clinical
      effect after irradiation and the inaccuracy of targeting because depth recording
      is not available. Therefore, we sought to determine the optimum target in gamma
      thalamotomy based on the results of conventional selective thalamotomy with
      reference to the AC-PC line. To obtain indirect support for the appropriateness
      of the optimum target, we performed depth recording around the region of the
      estimated optimum target based on the results of conventional thalamotomy. Four
      patients with tremor caused by Parkinson's disease or essential tremor were used
      as subjects after they gave their fully informed consent. The targets were
      determined as points 6-8 mm anterior to the posterior commissure, 4-6 mm dorsal
      to the level of the intercommissural line, and 15-17 mm lateral from the midline.
      Rhythmic discharge time-locked to tremor and/or kinesthetic neurons were found
      within the expected target area in all patients. Finally, in all cases, the
      tremor was abolished without complications after coagulative lesions were made
      with dual coagulation needles to cover the supposed Vim zone according to the
      depth recording. We considered that the target point determined in the same way
      as in gamma thalamotomy is suitable from an anatomophysiological perspective.

PMID- 16088292
TI  - Parkinsonian voice acoustic analysis in real-time after stereotactic thalamotomy.
AB  - The voice acoustic structure in 7 male patients with Parkinson's disease was
      analyzed 1 week before and 1 week after right-sided thalamotomy. The voice signal
      of the 3-digit number 306 was analyzed in real-time using a digital frequency
      analyzer. The average value of intensity level during the initial segment of the
      speech signal became higher after thalamotomy (75.04 vs. 59.24 dB). The voice
      fundamental frequency increased from 104 to 122 Hz. Before the operation, the
      energy focus of the speech signal was 73.19 vs. 76.87 dB postoperatively. The
      voice formants F1 and F2 shifted to the higher energy and frequency regions. The
      total sound pressure level of the pronounced 3-digit number 306 became two times
      higher after operation. The overall fluency of pronunciation was improved.

PMID- 16088293
TI  - Usefulness of in vitro 1H magnetic resonance spectroscopy for the
      characterization of primary brain tumors: report of two cases.
AB  - Pathological diagnosis of brain tumors provides an index of brain disease
      severity and guides clinical practice in their treatment. Diagnoses are often
      made from biopsy material obtained using stereotactic techniques with the
      difficulty of making a histological diagnosis in small samples. In our
      experience, the estimation of the degree of malignancy on the basis of in vitro
      1H magnetic resonance spectroscopy (1H MRS) appears to well correlate with
      histology and clinical evolution. We report two cases with a discordance between
      the diagnoses on the basis of histology examination and in vitro 1H MRS whose
      evolution seems to correlate better with the data of 1H MRS.

PMID- 16088294
TI  - Are lifestyle interventions in the management of hypertension effective? How long
      should you wait before starting specific medical therapy? An ongoing debate.

PMID- 16088295
TI  - Visit frequency and hypertension.
AB  - The best return visit interval to achieve blood pressure control is currently
      unknown. This study investigates the relationship between return visit interval
      and percent change in blood pressure. We reviewed a cohort of hypertensive
      patient charts from two large, urban family practice offices. Four hundred twenty
      nine patients with 7910 intervals showed a mean return visit interval of 79.5
      days. Blood pressure control occurred during 34.5% of office visits. Pearson's r
      correlation coefficients between return visit interval and percent change in
      systolic and diastolic blood pressure demonstrated a small but statistically
      significant correlation. Shorter return visit intervals were associated with
      better percent changes in blood pressure. The return visit interval may be a
      simple and useful tool to improve management of hypertension.

PMID- 16088296
TI  - Left ventricular geometric patterns after 1 year of antihypertensive treatment.
AB  - Left ventricular hypertrophy increases the risk for cardiovascular target organ
      damage, myocardial infarction, and stroke. The authors assessed the patterns of
      ventricular adaptation in 107 essential hypertensives whose treatment had been
      withdrawn and its modification after 1 year of hypertension treatment. Blood
      pressure decreased from 158+/-17/96+/-12 mm Hg to 137+/-15/83+/-10 mm Hg (mean +/
      SD; p<0.001); 45% of the patients (49 of 107) had their blood pressure
      controlled below 140 mm Hg and 90 mm Hg. Although a significant decrease of left
      ventricular mass index was found in the study, the percentage of patients with
      normal left ventricular geometry at the completion of the study increased by only
      9% (27% to 36%, p>0.05). Left ventricular mass geometry improved in 31% of the
      patients, remained unaffected in 51%, and worsened in 18%. The data suggest that
      even while suboptimal antihypertensive treatment reduces left ventricular mass
      index, either left ventricular hypertrophy or concentric remodeling remains
      present in a significant number of patients at the end of a 1-year treatment
      period. The authors conclude that these patients should be considered as a
      subgroup at high risk and should be treated more aggressively.

PMID- 16088297
TI  - Single- or double-blind treatment With Balsamodendron mukul and nifedipine in
      hypertensive patients.
AB  - This study assessed and compared the effects of Balsamodendron mukul (an extract
      of the gum of a small tree) and nifedipine (a calcium-channel-blocking reference
      drug) on blood pressure, lipids, lipoproteins, and phospholipids in randomly
      selected patients with essential hypertension. Fifty-seven newly diagnosed
      hypertensive patients were randomly divided into three groups. They received
      either single-blind B. mukul (1.5 g/d) or single-blind nifedipine (10 mg/d)
      double-blind therapy with nifedipine (10 mg/d) and B. mukul (1.5 g/d) for 6
      weeks. These groups were compared with control subjects. On treatment with B.
      mukul, levels of systolic blood pressure, diastolic blood pressure, plasma total
      cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein
      cholesterol, triglycerides, free fatty acids, and phospholipid levels were
      significantly reduced, and high-density lipoprotein cholesterol levels were
      significantly elevated, as compared with untreated hypertensive patients.
      Combined therapy with B. mukul and nifedipine was more beneficial than the
      treatment with B. mukul alone. Our study suggests that B. mukul may be an
      effective antihypertensive and hypolipidemic agent.

PMID- 16088298
TI  - Excessive alcohol consumption and hypertension: clinical implications of current
      research.
AB  - Substantial evidence demonstrates that: 1) heavy alcohol consumption (three or
      more standard drinks per day) is associated with and predictive of hypertension;
      2) reduction in alcohol consumption is associated with a significant dose
      dependent lowering of mean systolic and diastolic blood pressure; and 3)
      physician advice can reduce heavy drinking in hypertensive patients. These
      findings suggest that the routine evaluation of alcohol consumption in
      hypertensive patients is warranted. The Alcohol Use Disorders Identification Test
      C (AUDIT-C), a brief, three-question screening test, is useful in this regard.
      Alcohol biomarkers can also play a role in detecting and monitoring heavy
      drinking in hypertensive patients whose self-reports on the AUDIT-C are suspect.
      Carbohydrate-deficient transferrin, a new alcohol biomarker with high
      specificity, can provide objective data for feedback and counseling. A routine
      search for excessive use of alcohol, along with brief interventions and
      monitoring, can have a major impact on reducing the prevalence of hypertension in
      the general population.

PMID- 16088299
TI  - Are chlorthalidone and hydrochlorothiazide equivalent blood-pressure-lowering
      medications?

PMID- 16088300
TI  - Ethnicity and blood pressure.
AB  - The prevalence, impact, and control of hypertension differ across racial and
      ethnic subgroups in the United States population. Whether race/ethnicity should
      be a significant consideration in the choice of individual antihypertensive drugs
      continues to be a topic of intense interest and debate. This brief review will
      discuss recent findings that bear on the management of hypertension in these
      special patient groups.

PMID- 16088301
TI  - Sitting on the evidence: what is the proper patient position for the office
      measurement of blood pressure?

PMID- 16088302
TI  - Aortic dissection.
AB  - Aortic root enlargement is generally asymptomatic, with few clinical clues, but
      may be observed as an incidental finding on a chest x-ray, echocardiogram, or
      contrast-enhanced computerized tomogram of the chest. Aortic dissection is one of
      the most feared complications of hypertension. A history of hypertension is
      commonly present, but the systolic blood pressure in type A dissection (proximal
      to the left subclavian artery) has been found to be less than 150 mm Hg in 64% of
      patients. However, 71% of type B dissections (distal to the left subclavian
      artery) present with a systolic blood pressure 150 mm Hg or higher (International
      Registry of Acute Aortic Dissection). Most frequently, onset of symptoms is in
      the daytime, especially between 6 a.m. and noon. Severe sharp chest pain that is
      abrupt in onset is the most likely presentation. Migrating pain is uncommon.
      Although a pulse deficit with decreased or absent carotid, brachial, or femoral
      pulses occurs in only 30% of patients, three or more deficits predict an in-house
      mortality of about 60%. A chest x-ray finding of a widened mediastinum is present
      in 62.6% of type A and 56% of type B dissections. Contrast-enhanced computerized
      tomography or transesophageal echocardiography is the most commonly performed
      procedure for diagnosis. In-house mortality has been found to be 32.5% in type A
      dissections and 13% in type B dissections.

PMID- 16088303
TI  - Analysis of recent papers in hypertension.

PMID- 16088304
TI  - Notes from the Editor-in-Chief ... transformation taking place at the Veterans
      Health Administration.

PMID- 16088305
TI  - The Veterans Health Administration: quality, value, accountability, and
      information as transforming strategies for patient-centered care.
AB  - The Veterans Health Administration is the United States' largest integrated
      health system. Once disparaged as a bureaucracy providing mediocre care, the
      Department of Veterans Affairs (VA) reinvented itself during the past decade
      through a policy shift mandating structural and organizational change,
      rationalization of resource allocation, explicit measurement and accountability
      for quality and value, and development of an information infrastructure
      supporting the needs of patients, clinicians, and administrators. Today, the VA
      is recognized for leadership in clinical informatics and performance improvement,
      cares for more patients with proportionally fewer resources, and sets national
      benchmarks in patient satisfaction and for 18 indicators of quality in disease
      prevention and treatment.

PMID- 16088306
TI  - The VA advantage: the gold standard in clinical informatics.
AB  - How does a healthcare organization undergo such transformation as described in
      the lead paper in eight short years? Just imagine being part of an organization
      that achieved the following transformations: (1) reduction in hospital and long
      term-care beds from 92,000 to 53,000 and an increase in outpatient clinics from
      200 to 850 (2) a 75% increase in the number of patients treated on an annual
      basis (from 2.8 million to 4.9 million) with only a 32% cumulative increase in
      budget (from $19 billion to $25 billion) (3) clinicians who have access to
      complete medical records for almost all patient visits and all care settings (4)
      clinicians who willingly enter medication orders 94% of the time (5) patients who
      are increasingly satisfied with their care, ranking the service consistently
      higher than the competition (6) improved patient outcomes, achieved at costs 25%
      less than the competition. Such transformation is impossible to achieve without
      vision, leadership, talent, teamwork and tools. I will restrict my comments to a
      discussion of the tools, specifically the VA's clinical information system
      (VistA, HealtheVet, My HealtheVet. However, it is important to note that the
      results described in this paper would not be possible without the VA's
      transformational leadership and dedicated teams of professionals capable of
      executing the vision.

PMID- 16088307
TI  - Lessons learned from the Veterans Health Administration.
AB  - Veteran Affairs (VA) Veterans Health Administration (VHA) is the largest
      integrated healthcare system in the United States, treating close to five million
      patients annually through its 163 hospitals and 15,000 physicians (Kolonder
      2003). Comparable in operational size to the province of Ontario, it is an
      efficient and innovative system for Canadians to learn from. In particular, the
      VHA is an excellent example of healthcare transformation through the use of
      information technology (IT).

PMID- 16088308
TI  - The VHA's commitment to accountability: a "Third Way" for Medicare?
AB  - Albertans are seeking a "Third Way" for Medicare; Canadians generally are
      struggling with the issue of "sustainability." The transformation of the Veterans
      Health Administration suggests that the key to sustainability is not levels of
      spending per se but public confidence that a system delivers value for money. The
      VHA regained confidence by defining its value ("Quality") and being accountable
      for delivering it. The US health system is no model for Canada, but Quality and
      Accountability should be part of a Third Way, incorporating the best ideas from
      the US into a renewed public system.

PMID- 16088309
TI  - Transforming cancer services in Ontario: a work in progress.
AB  - Cancer Care Ontario (CCO) is the largest provincial cancer agency in Canada, with
      a long and rich history as a specialized service entity within a generic delivery
      system in Ontario. CCO's evolution has been well characterized by Hayter (1998),
      and described by us previously (Sullivan et al. 2003, 2004). Once criticized as a
      very inward-looking body with a mixed record in solving a series of radiation
      waiting-time crises, CCO has reinvented itself over the past three years in ways
      that are very similar to the transformation of the Veterans Health
      Administration.

PMID- 16088310
TI  - Quality, value, accountability and information as transforming strategies for
      patient-centred care: a commentary from an international perspective.
AB  - The reviewed paper describes how one of the largest integrated healthcare systems
      in the US has successfully transformed itself to provide 21st-century healthcare.
      Even though there are other examples of successful transformation of public
      health services, it is difficult for large, bureaucratic systems to change, and a
      substantial number of ministries of health or social security health systems in
      the developing world are run under the assumption that change is very difficult
      if not impossible to achieve. The VA has significant differences and more
      financial resources compared to most of the developing world public health
      institutions; but still, change is often not only about money, but also about
      strategic direction, commitment and leadership. On the basis of the main
      strategies used by the VA in its transformation process, the author makes some
      comments and suggestions for improving developing world healthcare organizations
      through lessons learned from the VA management strategies. Demand-driven or
      patient-centred systems are key for success and for the buy-in and involvement of
      the population and users of healthcare services, but this is easier said than
      done, especially in developing healthcare systems with immature information
      systems, access mechanisms and knowledge management. There is a belief in general
      that large bureaucratic organizations have a hard time adapting and transforming
      in response to the rapid change of society, technology and most importantly the
      needs and expectations of their users. The article describes how the largest
      integrated healthcare organization in the United States, the Veterans Health
      Administration, has undertaken changes that have turned it into a modern, well
      managed organization that outperforms its competitors and has significantly
      increased its efficiency and users' satisfaction.

PMID- 16088311
TI  - Can a healthcare system be transformed? Lessons from the past decade at the
      Veterans Health Administration.
AB  - The Veterans Health Administration in the United States has wrought a miracle.
      After 10 years of transformation and strategic reinvestment, their healthcare
      system has become more community-oriented, provides more services overall and
      costs less per patient. In this commentary, the systems of the Veterans Health
      Administration and of Canada are compared and contrasted with regard to three key
      issues: community orientation, patient-centredness and the role of information
      technology.

PMID- 16088312
TI  - The transformation experience of the Veterans Health Administration and its
      relevance to Canada.
AB  - Over the past few years, there has been a steady stream of visitors to Canada
      from the US Veterans Health Administration (VA). Led by the former Under
      Secretary for Health in the Department of Veterans Affairs, Dr. Ken Kizer, they
      come to tell the remarkable story of how the VA transformed itself from a
      hospital-based bureaucracy described as "dangerous, dirty and scandal-ridden" to
      a healthcare system for veterans recognized for its high-quality, patient-centred
      care. It is a fascinating story of how a publicly funded healthcare service
      changed its entire approach to patient care with a quality improvement lens at
      its core. Fifteen years ago, critics of the VA called for its complete
      privatization as the only solution to fixing its problems. A team of quality
      champions set out to prove otherwise. Canada has some lessons to learn. The VA is
      a compelling role model for Canadian reformers, in large measure, due to its
      public sector character.

PMID- 16088313
TI  - Human T cell leukemia virus type 1: the role of Tax in leukemogenesis.
AB  - Human T cell leukemia virus type 1 (HTLV-1) is a complex human retrovirus which
      is the causative agent of adult T cell leukemia (ATL). ATL occurs in about 4% of
      carriers and develops after a long latent period. Although the precise mechanism
      of HTLV-1 oncogenesis remains unclear, the pathogenesis has been linked to the
      pleiotropic activity of the viral transcriptional activator protein Tax. Tax has
      been shown to regulate viral and cellular gene expression and to functionally
      interfere with proteins involved in cell-cycle progression and DNA repair. This
      review will focus on the role of Tax in p53 inhibition.

PMID- 16088314
TI  - Hemopoietic cell transplantation for the myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are hemopoietic stem cell disorders, and
      hemopoietic stem cell transplantation is currently the only therapeutic modality
      with curative potential. Among patients with less advanced/low-risk MDS (<5%
      marrow blasts), 3-year survivals of 65--70% are achievable with HLA-identical
      related and unrelated donors. The overall probability of disease recurrence in
      these patients is <5%. Among patients with more advanced disease (>or=5% marrow
      blasts), the relapse probability is higher, ranging from 10--40%, and relapse
      free survival is correspondingly lower. The criteria proposed by the
      International Prognostic Scoring System, derived from non-transplanted patients,
      also predict survival following transplantation. The development of reduced
      intensity conditioning regimens and modification of conventional regimens, all
      aimed at optimizing the transplant approach, have permitted successful
      hemopoietic stem cell transplants even in patients 60--70 years of age. Improved
      survival with transplants from unrelated volunteer donors reflects to a large
      extent selection of donors on the basis of high resolution (allele-level) HLA
      typing. Graft-versus-host disease and associated problems remain major challenges
      after allogeneic transplantation. Autologous stem cell transplantation may be
      beneficial for selected patients who have obtained complete remissions with
      conventional chemotherapy.

PMID- 16088315
TI  - Peptide-based approaches to treat asthma, arthritis, other autoimmune diseases
      and pathologies of the central nervous system.
AB  - In this review we focus on peptide- and peptidomimetic-based approaches that
      target autoimmune diseases and some pathologies of the central nervous system.
      Special attention is given to asthma, allergic rhinitis, osteoarthritis, and
      Alzheimer's disease, but other related pathologies are also reviewed, although to
      a lesser degree. Among others, drugs like Diacerhein and its active form Rhein,
      Pralnacasan, Anakinra (Kineret), Omalizumab, an antibody "BION-1", directed
      against the common beta-chain of cytokine receptors, are described below as well
      as attempts to target beta-amyloid peptide aggregation. Parts of the review are
      also dedicated to targeting of pathologic conditions in the brain and in other
      tissues with peptides as well as methods to deliver larger molecules through the
      "blood--brain barrier" by exploring receptor-mediated transport, or elsewhere in
      the body by using peptides as carriers through cellular membranes. In addition to
      highlighting current developments in the field, we also propose, for future drug
      targets, the components of the inflammasome protein complex, which is believed to
      initiate the activation of caspase- 1 dependent signaling events, as well as
      other pathways that signal inflammation. Thus we discuss the possibility of
      targeting inflammasome components for negative or positive modulation of an
      inflammatory response.

PMID- 16088316
TI  - Monocyte-related immunopathologies in trauma patients.
AB  - Mechanical trauma is one of the most important causes of morbidity in the
      developed world. The response of the immune system to mechanical insult is of
      paramount importance for the patient's recovery. Shortly after trauma, the
      indiscriminate systemic inflammatory response syndrome (SIRS) is mediated by
      circulating monocytes (M Os) and other innate immunity components. Then acquired
      immunity, limited to the offending pathogen and the site of injury, gradually
      preponderates. SIRS is followed by the compensatory anti-inflammatory response
      syndrome (CARS), where the initial inflammatory response is quenched by anti
      inflammatory mediators. This precisely regulated process of immune system
      activation in response to trauma can be easily deviated, resulting in multiorgan
      failure (MOF) and increased mortality. Excessive activation of inflammatory M Os
      in the SIRS phase, premature or exorbitant CARS, a predominance of macrophages
      (Macs) in the blood stream and peripheral tissues, as well as a depletion of
      dendritic cells are often seen in trauma patients and contribute to the
      development of MOF. Here we explore several mechanisms of pathological MO;
      activation in patients with severe mechanical traumatic injury without
      accompanying sepsis.

PMID- 16088317
TI  - Nanovesicular vaccines: exosomes.
AB  - Exosomes are small membrane vesicles derived from late endosome. They are about
      30--100 nm in diameter. The secretion of exosomes is a process in which
      multivesicular bodies fuse with the cell membrane, and all cells that contain
      multivesicular endocytic compartments could theoretically secrete exosomes. The
      surprising biological functions of exosomes are only slowly being unveiled, but
      it is already clear that they serve to remove obsolete membrane proteins and act
      as messages of inter-cellular communication. Exosomes derived from tumor or
      antigen-presenting cells have been extensively investigated. They are released
      into the extracellular environment and fuse with the membranes of neighboring
      cells, delivering membrane and cytoplasmic proteins from one cell to another.
      Exosomes carry immunorelevant structures which play important roles in immune
      response, such as MHC molecules, costimulatory molecules, heat shock proteins,
      and naive tumor antigens. Therefore they have been suggested as potential
      vaccines. Consequently, exosomes have shown considerable anti-tumor effect in
      several studies and are in phase I clinical trials.

PMID- 16088318
TI  - The soluble CTLA-4 receptor: a new marker in autoimmune diseases.
AB  - A soluble form of cytotoxic T lymphocyte-associated antigen-4 (sCTLA-4) was
      recently found and shown to possess B7 binding activity. sCTLA-4 is generated by
      alternatively spliced mRNA. The mRNA encoding sCTLA-4 consists of 3 exons: exon 1
      encodes a leader peptide, exon 2 the ligand binding domain, and exon 4 the
      cytoplasmic tail, but it lacks the transmembrane domain encoded by exon 3. The
      altered transcript is detected in resting CD4 and CD8 T cells and its expression
      is inhibited after 24--48 h of activation and returns to the prestimulation level
      after 72--120 h of activation. Low levels of sCTLA-4 have been detected in normal
      human serum and increased serum levels have been observed in several autoimmune
      diseases (e.g. Graves' disease, myasthenia gravis, systemic lupus erythematosus,
      and systemic sclerosis). The biological significance of increased sCTLA-4 serum
      level has not been clarified. On one hand, sCTLA-4 may bind B7 expressed on
      antigen-presenting cells and is thus able to interfere with the B7:CD28-mediated
      costimulation of T cell responses. On the other hand, sCTLA-4 may also be capable
      of interfering with B7:CTLA-4 interactions, thereby blocking the negative signal
      imparted via the full-length form of CTLA-4. This double-edged nature of B7
      blocking by sCTLA-4 may result in different outcomes of the clinical course of
      disease.

PMID- 16088319
TI  - A mouse monoclonal antibody to the TSHR.
AB  - INTRODUCTION: Mouse monoclonal antibodies (mAbs) with the ability to inhibit
      thyrotropin (TSH) binding to the TSH receptor (TSHR) are useful tools to study
      TSH-TSHR interaction. The 3C3 mAb we produced was found to inhibit binding of TSH
      to human (h)TSHR but not to porcine (p)TSHR. MATERIAL/METHODS: Purified 3C3
      immunoglobulin G (IgG) and its antibody-binding fragment were prepared using
      standard methods and their ability to inhibit TSH binding to hTSHR or pTSHR was
      analyzed using a coated tube assay. The TSHR epitope reactive with 3C3 IgG was
      determined using Western blotting, ELISA based on peptides corresponding to the
      TSHR sequence, and the SPOT synthesis technique. RNA was isolated from 3C3
      hybridoma cells and the mAb variable (V) region genes were sequenced and
      analyzed. RESULTS: 3C3 mAb had a 1 x 108 l/mol binding affinity to the hTSHR as
      assessed by Scatchard analysis. 3C3 reacted with the hTSHR region between amino
      acids (aa) 212-230, and two aa differences were found between the corresponding
      regions in the hTSHR and pTSHR. The light chain (LC) genes of 3C3 were derived
      from the Vk21 germ-line (97.6% homology) and Jk2 genes. The heavy chain (HC)
      genes were from the V130 germ-line (94.6% homology) combined with a D gene (not
      identified) and JH3 gene. The replacement/ silent mutation ratios of 6.0 and 6.5
      for the LC and the HC V regions, respectively, indicated that 3C3 underwent
      antigen-driven maturation. CONCLUSIONS: Mouse mAbs of this type should be useful
      in studying the interactions between the TSHR, TSH, and mAbs in more detail.

PMID- 16088320
TI  - Prevalence of the intron 22 inversion of the factor VIII gene and inhibitor
      development in Polish patients with severe hemophilia A.
AB  - INTRODUCTION: Patients with severe hemophilia A often develop inhibitors
      (antibodies) against transfused factor VIII. MATERIAL/METHODS: One hundred
      thirteen Polish patients with severe hemophilia A, who had been treated on demand
      with cryoprecipitate until 1992 and exclusively with factor VIII concentrates
      after 1995, were examined for intron 22 inversion by Southern blotting and the
      presence and magnitude of inhibitor activity in blood as determined by the
      Bethesda assay. The patients' ages ranged 4--67 years (mean: 33.7+/-12.4 years,
      median: 32 years). RESULTS: The number of patients with the inversion amounted to
      57, while in 56 patients the mutation types were unknown; 47 patients had a
      distal and 10 patients a proximal type of inversion. Thirteen patients with
      inversions (22.8%) were found to have inhibitor in their blood. Most patients (14
      out of 15) who developed inhibitors in the course of cryoprecipitate therapy were
      high responders. Conversely, 4 of 5 patients treated between 1992 and 1995 with
      both cryoprecipitate and intermediate-purity factor VIII concentrates were low
      responders. One multitransfused patient who had remained inhibitor-free on
      cryoprecipitate therapy developed inhibitor after receiving a large dose of
      factor VIII concentrate during surgery. None of these 5 patients developed
      inhibitors during their 12--40 years of treatment with cryoprecipitate,
      suggesting that it was less immunogenic than factor VIII concentrates.
      CONCLUSIONS: The prevalence of the intron 22 inversion mutation of the factor
      VIII gene in Polish hemophiliacs is similar to that in other European countries.
      Treatment regimens with either cryoprecipitate or virus-inactivated plasma
      derived factor VIII concentrates may affect inhibitor formation in hemophilia A
      patients.

PMID- 16088321
TI  - Assessment of selected co-stimulatory, adhesion and activatory molecules and
      cytokines of Th(1)/Th(2) balance in acute lymphoblastic leukemia in children.
AB  - INTRODUCTION: Recent years have seen a rise in the importance of cytokine
      production and co-stimulatory/activatory molecule expression in the immune
      response in leukemia. The aim of our study was to assess the function of T
      lymphocytes in children with acute lymphoblastic leukemia (ALL) during remission
      induction based on selected cytokine and co-stimulatory/activatory molecule
      expression. MATERIAL/METHODS: The study group consisted of 50 children with ALL
      (B cell precursor). Peripheral blood samples were taken before treatment (day 0),
      after the prednisone prophase (day 8), and during (day 15) and after (day 33)
      remission induction. The percentages of T cells with interferon (IFN)-gamma
      (Th(1)), interleukin (IL)-4 (Th(2)) and IL-2 receptor (IL-2R), CD28, CTLA-4,
      CD38, ICAM-1, and HLA-DR expression were assessed by tricolor flow cytometry.
      RESULTS: At the time of diagnosis we noted higher percentages of T cells with
      adhesion molecule ICAM-1, activation molecule CD38 expression, and an increased
      population of Th(2 )cells (IL-4) compared with the control group. During and
      after remission induction we observed a decreased population of CD38(+) T cells,
      elevated percentages of helper T lymphocytes with IL-2R expression, and a rise in
      helper T lymphocytes producing IFN-gamma (Th(1)). During fever/infection, higher
      levels of activated T lymphocytes (CD4(+)HLA-DR(+), CD8(+)HLA-DR(+)), a rise in
      Th1, and no change in Th(2 )populations were observed. CONCLUSIONS: The results
      suggest T cell activation and Th(2 )predominance at the time of diagnosis and
      during remission induction in ALL in children. These results confirm the
      involvement of cellular immunity in the leukemic process and can be used in
      immune therapy in leukemia.

PMID- 16088323
TI  - The 3(rd )Annual International Umbilical Cord Blood Transplantation Symposium.

PMID- 16088322
TI  - Simultaneous transplantation of two allogeneic units of cord blood in an adult
      patient with acute myeloblastic leukemia: a case report.
AB  - INTRODUCTION: The major obstacle to the therapeutic use of hematopoietic
      transplantation is the unavailability of matched, unrelated marrow donors for the
      large number of potential patients, although all of them have the chance to find
      sufficiently matched, unrelated cord blood units. However, the use of cord blood
      as a source of cells for transplantation is limited by its cell number, usually
      below 1 billion, which allows for routine transplantation only in children
      weighting less than 30 kg, while most potential recipients possess a higher body
      mass. This led to the idea of the simultaneous use of several units of cord blood
      which, combined, would fulfill the requirements for the necessary cell number for
      an adult recipient. MATERIAL/METHODS: We attempted to simultaneously transplant
      an adult patient with refractory acute myeloblastic leukemia utilizing two
      different cord blood units, one fully matched and one mismatched at one locus.
      RESULTS: The patient became reconstituted with only one unit, the mismatched, as
      determined using microsatellite markers, and had no signs of relapse of leukemia.
      Unfortunately, he died of persistent fungal (brain aspergilloma) infection on day
      +103. CONCLUSIONS: The successful engraftment may suggest that a method based on
      the principle of using more than one cord blood unit for transplantation is
      feasible in large adult patients and may reach routine application.

PMID- 16088324
TI  - The 10th congress of the European Hematology Association.

PMID- 16088325
TI  - Modulation of alpha-crystallin chaperone activity in diabetic rat lens by
      curcumin.
AB  - PURPOSE: A decline in the chaperone-like activity of eye lens alpha-crystallin in
      diabetic conditions has been reported. In this study, we investigated whether
      curcumin, a dietary antioxidant, can manipulate the chaperone-like activity of
      alpha-crystallin in diabetic rat lens. METHODS: A group of rats received ip
      injection of streptozotocin (STZ; 35 mg/kg body weight in buffer) to induce
      hyperglycemia, while another group of rats received only buffer as vehicle and
      served as control. STZ-treated rats were assigned to 3 groups and fed either no
      curcumin or 0.002% or 0.01% curcumin, respectively. Cataract progression due to
      hyperglycemia was monitored with a slit lamp biomicroscope. At the end of 8 weeks
      animals were sacrificed and lenses were collected. alphaH- and alphaL-crystallins
      from a set of pooled lenses in each group were isolated by gel filtration.
      Chaperone activity, hydrophobicity, and secondary and tertiary structure of
      alphaH- and alphaL-crystallins were assessed by light scattering/spectroscopic
      methods. RESULTS: A decrease in chaperone-like activity of alphaH- and alphaL
      crystallins was observed in STZ-treated diabetic rats. The declined chaperone
      like activity due to hyperglycemia was associated with reduced hydrophobicity and
      altered secondary and tertiary structure of alphaH- and alphaL-crystallins.
      Interestingly, alphaH- and alphaL-crystallins isolated from curcumin fed diabetic
      rat lenses had shown improved chaperone-like activity as compared to alphaH- and
      alphaL-crystallins from untreated diabetic rat lens. Feeding of curcumin
      prevented the alterations in hydrophobicity and structural changes due to STZ
      induced hyperglycemia. Modulation of functional and structural properties by
      curcumin was found to be greater with the alphaL-crystallin than alphaH
      crystallin. Loss of chaperone activity of alpha-crystallin, particularly alphaL
      crystallin, in diabetic rat lens could be attributed at least partly to increased
      oxidative stress. Being an antioxidant, curcumin feeding has prevented the loss
      of alpha-crystallin chaperone activity and delayed the progression and maturation
      of diabetic cataract. CONCLUSIONS: We demonstrate that curcumin, at the levels
      close to dietary consumption, prevented the loss of chaperone-like activity of
      alpha-crystallin vis-a-vis cataractogenesis due to diabetes in rat lens.

PMID- 16088326
TI  - An ENU-induced mutation in Rs1h causes disruption of retinal structure and
      function.
AB  - PURPOSE: The 44TNJ mutant mouse was generated by the Tennessee Mouse Genome
      Consortium (TMGC) using an ENU-based mutagenesis screen to produce recessive
      mutations that affect the eye and brain. Herein we present its retinal phenotype
      and genetic basis. METHODS: Fourth generation offspring (G4) and confirmed
      mutants were examined using slit lamp biomicroscopy, funduscopy, histology,
      immunohistochemistry, and electroretinography (ERG). 44TNJ mutant mice were
      crossed to C3BLiA or DBA/2 mice for chromosomal mapping purposes. Linkage
      analysis by PCR-based microsatellite marker genotyping was used to identify the
      disease locus. The Rs1h cDNA and its genomic DNA were sequenced directly.
      RESULTS: The 44TNJ pedigree was the first mutant pedigree identified by the
      ocular phenotyping domain of the TMGC. Examination of the fundus revealed
      numerous small and homogeneous intraretinal microflecks in the peripapillary
      region, which became courser and more irregular in the periphery. Males were
      typically more affected than females. Histology and immunohistochemistry revealed
      a disruption of the lamination of the retina, particularly at both margins of the
      outer nuclear layer, along with reduced calbindin immunostaining. ERG analyses
      revealed reduced amplitudes of both a-waves and b-waves. Linkage analysis mapped
      the 44TNJ mutation to the X chromosome close to the marker DXMit117. Sequence
      analysis of the positional candidate gene Rs1h revealed a T->C exchange at the
      second base of intron 2 of the Rs1h gene. CONCLUSIONS: We have generated and
      characterized a mutant mouse line that was produced using ENU-based mutagenesis.
      The 44TNJ pedigree manifests with photoreceptor dysfunction and concurrent
      structural and functional aberrations at the post-receptoral level. Genetic
      analysis revealed a mutation in Rs1h, making this the first murine model of X
      linked retinoschisis in which the gene is expressed.

PMID- 16088327
TI  - Support for the association between the rare functional variant I425V of the
      serotonin transporter gene and susceptibility to obsessive compulsive disorder.

PMID- 16088328
TI  - Polymorphisms in FKBP5 are associated with peritraumatic dissociation in
      medically injured children.

PMID- 16088329
TI  - The SNAP25 gene as a susceptibility gene contributing to attention-deficit
      hyperactivity disorder.
AB  - The synaptosomal-associated protein of 25 kDa gene (SNAP25) has been suggested as
      a genetic susceptibility factor in attention-deficit hyperactivity disorder
      (ADHD) based on the mouse strain coloboma. This strain is hemizygous for the
      SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but
      not to methylphenidate. Previously, we reported association of SNAP25 and ADHD
      using two polymorphisms. To further investigate this gene, we screened the exons
      for DNA variation and genotyped ten additional polymorphisms in an expanded
      sample of families from Toronto and a second sample of families collected in
      Irvine, CA. Significant results were observed in the Toronto sample for four
      markers, although not in the Irvine sample. The paper discusses the possible
      influence of the selection criteria on these differential results. The Irvine
      sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas
      the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the
      Toronto sample indicated that the differential results were not attributable to
      ADHD subtype. Differences in ethnicity, differential medication response, and
      other clinical characteristics of the samples cannot be ruled out at this time.
      Quantitative analysis of the dimensions of hyperactivity/impulsivity and
      inattention in the Toronto sample found that both behavioral traits were
      associated with SNAP25. Our findings continue to support SNAP25 in the
      susceptibility to ADHD.

PMID- 16088330
TI  - A potential novel marker for human prostate cancer: voltage-gated sodium channel
      expression in vivo.
AB  - Functional expression of voltage-gated sodium channel alpha-subunits
      (VGSCalphas), specifically Nav1.7, is associated with strong metastatic potential
      in prostate cancer (CaP) in vitro. Furthermore, VGSC activity in vitro directly
      potentiates processes integral to metastasis. To investigate VGSCalpha expression
      in CaP in vivo, immunohistochemistry and real-time PCR were performed on human
      prostate biopsies (n>20). VGSCalpha immunostaining was evident in prostatic
      tissues and markedly stronger in CaP vs non-CaP patients. Importantly, RT-PCRs
      identified Nav1.7 as the VGSCalpha most strikingly upregulated (approximately 20
      fold) in CaP, and the resultant receiver-operating characteristics curve
      demonstrated high diagnostic efficacy for the disease. It is concluded that
      VGSCalpha expression increases significantly in CaP in vivo and that Nav1.7 is a
      potential functional diagnostic marker.

PMID- 16088331
TI  - Different forms of obesity as a function of diet composition.
AB  - OBJECTIVE: To characterize the phenotype of obesity on a high-carbohydrate diet
      (HCD) as compared to a high-fat diet (HFD) or moderate-fat diet (MFD). METHODS
      AND PROCEDURES: In four experiments, adult Sprague-Dawley rats (275-300 g) were
      maintained for several weeks on a: (1) HFD with 50% fat; (2) balanced MFD with
      25% fat; or (3) HCD with 10% fat/65% carbohydrate. Then, based on the amount of
      body fat accumulated in four dissected fat pads, the animals were subgrouped as
      lean (lowest tertile) or obese (highest tertile) and characterized with multiple
      measures. RESULTS: The obese rats of these diet groups, with 70-80% greater body
      fat than the lean animals, exhibited elevated levels of leptin and insulin and
      increased activity of lipoprotein lipase in adipose tissue (aLPL), with no change
      in muscle LPL. Characteristics common to the obese rats on the HFD or MFD, but
      not seen on the HCD, were hyperphagia, elevated circulating levels of
      triglycerides (TG), nonesterified fatty acids (NEFA) and glucose, and a
      significant increase in beta-hydroxyacyl-CoA dehydrogenase (HADH) activity in
      muscle, reflecting its greater capacity to metabolize fat. This was accompanied
      by a significant increase in expression of the peptide, galanin (GAL), in the
      paraventricular nucleus (PVN), as measured by in situ hybridization and real-time
      quantitative PCR, and also in GAL peptide immunoreactivity. These measures of GAL
      were consistently, positively correlated with circulating TG levels and also with
      HADH activity in muscle. In contrast to these fat-associated changes, rats that
      became obese on an HCD maintained normal caloric intake and levels of TG, NEFA,
      and glucose. They also showed no change in PVN GAL mRNA or peptide. Instead, they
      exhibited a significant reduction in HADH activity compared to the lean animals,
      along with increased activity of phosphofructokinase in muscle, a key enzyme in
      glycolysis. CONCLUSION: Specific characteristics of obesity, including expression
      of hypothalamic peptides, are dependent upon diet composition. Whereas obesity on
      an HFD is associated with hyperphagia and elevated lipids, fat metabolism in
      muscle, and fat-stimulated peptides such as GAL, obesity on an HCD with a similar
      increase in body fat shows none of these characteristics and instead exhibits a
      metabolic pattern in muscle that favors carbohydrate over fat oxidation. These
      results suggest the existence of multiple forms of obesity with different
      underlying mechanisms that are diet dependent.

PMID- 16088332
TI  - A survey of the methods for the characterization of microbial consortia and
      communities.
AB  - A survey of the available literature on methods most frequently used for the
      identification and characterization of microbial strains, communities, or
      consortia is presented. The advantages and disadvantages of the various
      methodologies were examined from several perspectives including technical,
      economic (time and cost), and regulatory. The methods fall into 3 broad
      categories: molecular biological, biochemical, and microbiological. Molecular
      biological methods comprise a broad range of techniques that are based on the
      analysis and differentiation of microbial DNA. This class of methods possesses
      several distinct advantages. Unlike most other commonly used methods, which
      require the production of secondary materials via the manipulation of microbial
      growth, molecular biological methods recover and test their source materials
      (DNA) directly from the microbial cells themselves, without the requirement for
      culturing. This eliminates both the time required for growth and the biases
      associated with cultured growth, which is unavoidably and artificially selective.
      The recovered nucleic acid can be cloned and sequenced directly or subpopulations
      can be specifically amplified using polymerase chain reaction (PCR), and
      subsequently cloned and sequenced. PCR technology, used extensively in forensic
      science, provides researchers with the unique ability to detect nucleic acids
      (DNA and RNA) in minute amounts, by amplifying a single target molecule by more
      than a million-fold. Molecular methods are highly sensitive and allow for a high
      degree of specificity, which, coupled with the ability to separate similar but
      distinct DNA molecules, means that a great deal of information can be gleaned
      from even very complex microbial communities. Biochemical methods are composed of
      a more varied set of methodologies. These techniques share a reliance on gas
      chromatography and mass spectrometry to separate and precisely identify a range
      of biomolecules, or else investigate biochemical properties of key cellular
      biomolecules. Like the molecular biological methods, some biochemical methods
      such as lipid analyses are also independent of cultured growth. However, many of
      these techniques are only capable of producing a profile that is characteristic
      of the microbial community as a whole, providing no information about individual
      members of the community. A subset of these methodologies are used to derive
      taxonomic information from a community sample; these rely on the identification
      of key subspecies of biomolecules that differ slightly but characteristically
      between species, genera, and higher biological groupings. However, when the
      consortium is already growing in chemically defined media (as is often the case
      with commercial products), the rapidity and relatively low costs of these
      procedures can mitigate concerns related to culturing biases. Microbiological
      methods are the most varied and the least useful for characterizing microbial
      consortia. These methods rely on traditional tools (cell counting, selective
      growth, and microscopic examination) to provide more general characteristics of
      the community as a whole, or else to narrow down and identify only a small subset
      of the members of that community. As with many of the biochemical methods, some
      of the microbiological methods can fairly rapidly and inexpensively create a
      community profile, which can be used to compare 2 or more entire consortia.
      However, for taxonomic identification of individual members, microbiological
      methods are useful only to screen for the presence of a few key predetermined
      species, whose preferred growth conditions and morphological characteristics are
      well defined and reproducible.

PMID- 16088333
TI  - Molecular analysis of Shigella boydii O1 O-antigen gene cluster and its PCR
      typing.
AB  - Shigella is an important human pathogen and is closely related to Escherichia
      coli. O-antigen is the most variable part of the lipopolysaccharide on the cell
      surface of Gram-negative bacteria and plays an important role in pathogenicity.
      The O-antigen gene cluster of S. boydii O1 was sequenced. The putative genes
      encoding enzymes for rhamnose synthesis, transferases, O-unit flippase, and O
      unit polymerase were identified on the basis of homology. The O-antigen gene
      clusters of S. boydii O1 and E. coli O149, which share the same O-antigen form,
      were found to have the same genes and organization by adjacent gene PCR assay.
      Two genes specific for S. boydii O1 and E. coli O149 were identified by PCR
      screening against E. coli- and Shigella-type strains of the 186 known O-antigen
      forms and 39 E. coli clinical isolates. A PCR sensitivity of 103 to 104 CFU/mL
      overnight culture of S. boydii O1 and E. coli O149 was obtained. S. boydii O1 and
      E. coli O149 were differentiated by PCR using lacZ- and cadA-based primers.

PMID- 16088334
TI  - Real-time quantitative PCR for enteric adenovirus serotype 40 in environmental
      waters.
AB  - Adenoviruses 40 and 41 have been recognized as important etiological agents of
      gastroenteritis in children. A real-time PCR method (TaqMan assay) was developed
      for rapid quantification of adenovirus 40 (Ad40) by amplifying an 88 bp sequence
      from the hexon gene. To establish a quantification standard curve, a 1090 bp
      hexon region of Ad40 was amplified and cloned into the pGEM-T Vector. A direct
      correlation was observed between the fluorescence threshold cycle number (Ct) and
      the starting quantity of Ad40 hexon gene. The quantification was linear over 6
      log units and the amplification efficiency averaged greater than 95%. Seeding
      studies using various environmental matrices (including sterile water, creek
      water, brackish estuarine water, ocean water, and secondary sewage effluent)
      suggest that this method is applicable to environmental samples. However, real
      time PCR was sensitive to inhibitors present in the environmental samples. Lower
      efficiency of PCR amplification was found in secondary sewage effluent and creek
      waters. Application of the method to fecal contaminated waters successfully
      quantified the presence of Ad40. The sensitivity of the real-time PCR is
      comparable to the traditional nested PCR assay for environmental samples. In
      addition, the real-time PCR assay offers the advantage of speed and insensitivity
      to contamination during PCR set up. The real-time PCR assay developed in this
      study is suitable for quantitative determination of Ad40 in environmental samples
      and represents a considerable advancement in pathogen quantification in aquatic
      environments.

PMID- 16088335
TI  - Biphenyl uptake by psychrotolerant Pseudomonas sp. strain Cam-1 and mesophilic
      Burkholderia sp. strain LB400.
AB  - We investigated the uptake of biphenyl by the psychrotolerant, polychlorinated
      biphenyl (PCB)-degrader, Pseudomonas sp. strain Cam-1 and the mesophilic PCB
      degrader, Burkholderia sp. strain LB400. The effects of growth substrates,
      metabolic inhibitors, and temperature on [14C]biphenyl uptake were studied.
      Biphenyl uptake by both strains was induced by growth on biphenyl, and was
      inhibited by dinitrophenol (DNP) and carbonyl cyanide m-chlorophenylhydrazone
      (CCCP), which are metabolic uncouplers. The Vmax and Km for biphenyl uptake by
      Cam-1 at 22 degrees C were 5.4 +/- 1.7 nmol x min(-1) x (mg of cell protein)(-1)
      and 83.1 +/- 15.9 micromol x L(-1), respectively. The Vmax and Km for biphenyl
      uptake by LB400 at 22 degrees C were 3.2 +/- 0.3 nmol x min(-1) x (mg of cell
      protein(-1)) and 51.5 +/- 9.6 micromol x L(-1), respectively. At 15 degrees C,
      the maximum rate for biphenyl uptake by Cam-1 and LB400 was 3.1 +/- 0.3 nmol x
      min(-1) x (mg of cell protein)(-1) and 0.89 +/- 0.1 nmol x min(-1) x (mg of cell
      protein)(-1), respectively. Thus, the maximum rate for biphenyl uptake by Cam-1
      at 15 degrees C was more than 3 times higher than that for LB400.

PMID- 16088336
TI  - The influence of Bacillus subtilis RB14-C on the development of Rhizoctonia
      solani and indigenous microorganisms in the soil.
AB  - The effect of soil inoculation with an antagonistic strain Bacillus subtilis RB14
      C on the development of Rhizoctonia solani and changes occurring in soil and
      rhizosphere microbial communities were studied. RB14-C was added to the soil as a
      water suspension of the cells or as a broth culture. Application of cell
      suspensions to non-planted soil reduced the number of culturable bacteria. The
      density of R. solani and the number of filamentous fungi were not significantly
      affected by RB14-C. A similar effect was observed in the rhizosphere of tomato
      plants growns in bacterized soil. Broth cultures of RB14-C suppressed R. solani 1
      d after inoculation, but after 3 d there was no difference in the pathogen
      density between soil amended with broth culture and control soil. In microcosm
      studies, cell suspensions of RB14-C also did not inhibit growth of R. solani on
      filters buried in soil. However, an inhibitory effect was obtained when a broth
      culture of the bacterium was used. The effect of RB14-C on fungal biomass was
      also estimated by measurement of ergosterol concentration in soil. It was found
      that ergosterol was mostly derived from R. solani and that there were no
      significant differences in its content between untreated soil and soil treated
      with RB14-C. The results suggest that suppression of Rhizoctonia damping-off by
      B. subtilis RB14-C probably is not related to the reduction of the pathogen
      population in the soil.

PMID- 16088337
TI  - An optimized enumeration method for sorbitol-fermenting Bifidobacteria in water
      samples.
AB  - With increased focus on watershed protection under the Surface Water Treatment
      Rule, indicators that discriminate among sources of microbial inputs (microbial
      source tracking) are needed to supplement the quantitative information provided
      by total and fecal coliform measurements for drinking water monitoring.
      Bifidobacteria are found in the digestive tract and feces of humans and other
      animals, and also in sewage. Sorbitol is a food additive used exclusively in food
      intended for human consumption. Therefore, the presence of sorbitol-fermenting
      Bifidobacteria in environmental waters can be indicative of sources of human
      fecal contamination. A series of media were evaluated using ATCC cultures of B.
      breve and B. adolescentis, feces from different animals, and domestic wastewater
      samples. The media evaluated were Human Bifid Sorbitol agar (HBSA), modified
      Human Bifid Sorbitol agar, Beerens Medium, modified Beerens Medium, Reinforced
      Clostridial agar, BIM-25 Medium, and modified BIM-25 Medium. Variables such as
      sample preservation, incubation time, different pH indicators, plating technique,
      and discontinuous exposure to sorbitol were also evaluated. A series of
      biochemical tests were used to confirm positive colonies enumerated on the
      various media. Membrane filtration and enumeration of sodium sulfite preserved
      samples on HBSA containing bromocresol purple using loose lidded plates for 48 h
      provided the best recoveries for presumptive positive colonies. A number of
      sorbitol-fermenters that were not Bifidobacteria were able to grow on all media
      tested, resulting in false-positives. Therefore, plating on HBSA should be
      followed by a confirmation step when monitoring for sorbitol-fermenting
      Bifidobacteria in environmental waters. A year-long sampling survey of a managed
      reservoir in Massachusetts provided field validation of the proposed methodology
      for sorbitol-fermenting Bifidobacteria as a human-related source tracking
      indicator tool.

PMID- 16088338
TI  - Multiple non-ribosomal peptide synthetase genes determine peptaibol synthesis in
      Trichoderma virens.
AB  - Trichoderma virens, an imperfect fungus, is used as a biocontrol agent to
      suppress plant disease caused by soilborne fungal pathogens. Antimicrobial
      peptides it produces include peptaibols of 11, 14, and 18 amino acids in length.
      These peptaibols were previously reported to be synthesized by a non-ribosomal
      peptide synthetase (NRPS) encoded by the Tex1 gene in strain Tv29-8. The present
      study examined the Tex1 homolog in a commercially relevant T. virens strain, G20.
      Although the gene in G20 was 99% identical in DNA sequence to Tex1 in the 15.8 kb
      compared, gene disruption results indicate that it is only responsible for the
      production of an 18-mer peptaibol, and not 11-mer and 14-mer peptaibols.
      Additional NRPS adenylate domains were identified in T. virens and one was found
      to be part of a 5-module NRPS gene. Although the multimodule gene is not needed
      for peptaibol synthesis, sequence comparisons suggest that two of the individual
      adenylate domain clones might be part of a separate peptaibol synthesis NRPS
      gene. The results indicate a significant diversity of NRPS genes in T. virens
      that is unexpected from the literature.

PMID- 16088340
TI  - Cannabis and suicidal behaviour among adolescents: a pilot study from Trinidad.
AB  - Cannabis use and suicidal behaviour are causes of adolescent morbidity and
      mortality worldwide. Changing trends in these behaviours in younger age groups,
      higher incidence, gender differences and sociocultural variations present an
      enormous challenge. There is no consensus whether these complex relationships are
      either a direct or an indirect effect due to other mental disorders, or a social
      response of disclosure of drug taking habits to family members and school
      authorities. This paper reviews the epidemiology of suicidal behaviour and
      cannabis use among adolescents and looks at the relationship of these behaviours
      regionally and internationally. The Caribbean islands have an established use of
      cannabis with higher suicidal rates, which provides an ideal setting to
      investigate the interrelationship of these disorders. Preliminary research
      findings in Trinidad indicate high rates of cannabis use among school students
      with higher rates in vocational schools compared to grammar schools. Utilising
      the CAPE questionnaire, depressive and psychotic experiences were common findings
      in adolescent cannabis users with a significant preponderance of depressive
      experiences (p<0.01). Our findings suggest that there is a convincing
      relationship between suicidal behaviour and cannabis use, the latter awakening
      depressive experiences. Suicidal behaviour and cannabis use are major public
      health problems and require a multidimensional approach with culturally competent
      preventive interactions. School based prevention programmes are necessary at the
      levels of parent-teacher partnership and classroom intervention. The treatment of
      adolescent disorders remains a major challenge of the future. Double disorders
      such as cannabis use and suicidal behaviour are uncharted areas and need novel
      approaches.

PMID- 16088341
TI  - Anti-inflammatory, antinociceptive, and gastric effects of Hypericum perforatum
      in rats.
AB  - The pharmacological activity of Hypericum perforatum was assessed using models of
      inflammation, nociception, and gastric mucosal injury in rats. H. perforatum was
      given systemically as well as orally. When administered systemically, H.
      perforatum (50-300 mg/kg, s.c.) produced a dose-related and significant
      inhibition of the edematogenic response to s.p. injection of carrageenan. The
      percentages of maximal inhibition by the above doses were 53.7, 61.3, and 75.3%,
      respectively (compared to 90% after 50 mg/kg fluoxetine and 60.7% after 72 mg/kg
      etodolac). In tests of nociception, H. perforatum, administered orally, displayed
      antinociceptive activity in the tail electric stimulation and hot plate tests.
      The antinociceptive activity was observed with 25 mg/kg and a maximal increase in
      hot plate latency by 50% (compared to 73.2 and 77.8% increases by 5 or 10 mg/kg
      fluoxetine, respectively). In contrast, the acetic acid-induced (0.6%, i.p.)
      writhing was significantly reduced by fluoxetine or etodolac, but not H.
      perforatum. Also, the nociceptive response caused by i.p. injection of capsaicin
      (1.6 microg/paw) was unaffected by H. perforatum, but reduced by fluoxetine.
      Injection of H. perforatum (50, 125, or 250 mg/kg, s.c.) to pylorus-ligated rats,
      decreased gastric acid secretion, but increased indomethacin-induced gastric
      mucosal lesions dose dependently. These results demonstrate that H. perforatum
      exhibits antiedematogenic and antinociceptive properties, which may be of value
      for the management of inflammatory painful conditions. The agent, however, causes
      gastric irritation and may aggravate that of NSAIDs.

PMID- 16088342
TI  - Childhood injury prevention: intervention in the Bedouin city of Rahat.
AB  - For several years, the National Center for Children's Health and Safety (Beterem)
      has worked on many levels to promote safety and prevent injury of the children in
      Israel. As part of intervention programs in 20 communities around Israel, this
      paper describes a 1-year, multidisciplinary, multistrategic childhood safety
      promotion and injury prevention project. The project took place in the Bedouin
      city of Rahat in the Southern part of Israel, the Negev, conducted by a local
      safety coordinator. This specific intervention study took place from March 2003
      to March 2004. The main goal was to identify hazards and dangerous obstacles in
      public places in Rahat, then remove or repair the obstacles found, in order to
      secure a safe public environment for children. "Obstacle" was defined as any
      barrier that could endanger the safety of a child. Ten examples are used to
      illustrate this applied research project, and 80% of the problems were solved
      within the project period (time to solve between 1 week to 3 months, depending on
      various factors). We recommend the involvement of a safety coordinator from the
      community to focus on safety hazards for children, the use of a documentation
      diary to log the time frame, and also the use of pictures to illustrate the
      hazards and the changes, or to use as arguments in the lobbying process.

PMID- 16088343
TI  - Protective effect of lipoic acid on micronuclei induction by cyclophosphamide.
AB  - The present study investigated the protective efficacy of DL-alpha-lipoic acid on
      the cyclophosphamide (CP)-induced clastogenicity using the in vivo micronucleus
      assay. Male Wistar rats of 140 +/- 20 g were categorized into eight groups. Five
      groups were administered CP (40 mg/kg body weight, intraperitonealy) to induce
      genotoxicity; four of these groups received a single intraperitoneal injection of
      lipoic acid at a dose of either 100 or 200 mg/kg body weight, and either 30 or 60
      min prior to CP administration. A vehicle-treated control group and lipoic acid
      control groups were also included. The number of micronucleated polychromatic
      erythrocytes (MNPCEs) was determined at 24 h after CP administration. In rats
      injected with CP, the frequency of MNPCEs in bone marrow and peripheral blood was
      increased significantly in comparison with the controls, and in rats treated with
      lipoic acid and CP, the number of MNPCEs was decreased significantly in
      comparison to those given CP alone. The chemoprotective effect was found to be
      stronger after the administration of lipoic acid at a dose of 200 mg/kg body
      weight than 100 mg/kg body weight dosage, indicating the dose-dependent
      protective effect of lipoic acid. However, the protection by lipoic acid was not
      dependent on the time intervals between lipoic acid and CP administration. Our
      results illustrate the protective effect of lipoic acid on the in vivo
      clastogenicity induced by CP.

PMID- 16088344
TI  - The arginine deiminase locus of Oenococcus oeni includes a putative arginyl-tRNA
      synthetase ArgS2 at its 3'-end.
AB  - Oenococcus oeni is the most important lactic acid bacteria of the winemaking
      process involved in malolactic fermentation. Most O. oeni strains are able to
      catabolyze arginine via the arginine deiminase (ADI) pathway. The arcR, A, B, C,
      D1, and D2 cluster of O. oeni bacteria has been characterized. Here, we completed
      the ADI locus sequence. Downstream of arcD2 gene, we found an additional gene
      which encodes a putative arginyl-tRNA synthetase (argS2). It is not the same
      arginyl-tRNA synthetase which was sequenced in O. oeni MCW strain.
      Transcriptional analyses have shown that argS2 was induced by arginine. In
      addition, systematic polymerase chain reaction amplification of each arc gene and
      argS2 has provided a characteristic feature of the ADI locus within the O. oeni
      species: all genes of ADI locus are present or absent according to the strains.

PMID- 16088346
TI  - Stability validation of seeding cell control parameters in large-scale hybridoma
      cell culture.
AB  - Stability and reproducibility of seeding cell performance in large-scale
      hybridoma cell culture has been reported by controlling only initial cell seeding
      density. The aim of the current study was to integrate multiple seeding cell
      control parameters to maintain stable and consistent cell physiological status
      for HAb18 cell expansion. Three parameters and their ranges were investigated,
      including initial cell seeding density in the range of 0.075-0.5 x 10(6) cells
      ml(-1), "timepost" after cell passage between 8 and 36 h, and duration of
      subculture up to 6 months after cell revival. Cell performance was tested at the
      1 L, 5 L, and 75 L scales. Desirable performance was found within the following
      parameter ranges: initial cell seeding density of 0.1-0.3 x 10(6) cells ml(-1),
      "timepost" after cell passage between 14 and 22 h, and duration of subculture
      within 3 months of cell revival. Our results showed that cell growth rate and
      antibody productivity of three batches at 1 L, 5 L, and 75 L scale were found to
      be stably maintained within a range of 0.036-0.047 h(-1) and 0.577-0.747 pg cell(
      1) h(-1), with the positivity rate of antigen-binding activity within 97-99.75%,
      and the intensity of fluorescence around 200. This study may provide a simple but
      effective method to maintain seeding cell physiological status stable and
      consistent by combining seeding cell control parameters.

PMID- 16088345
TI  - New cold-adapted lipase from Photobacterium lipolyticum sp. nov. that is closely
      related to filamentous fungal lipases.
AB  - A Photobacterium strain, M37, showing lipolytic activity, was previously isolated
      from an intertidal flat of the Yellow Sea in Korea and identified as
      Photobacterium lipolyticum sp. nov. In the present study, the corresponding gene
      was cloned using the shotgun method. The amino acid sequence deduced from the
      nucleotide sequence (1,023 bp) corresponded to a protein of 340 amino acid
      residues with a molecular weight of 38,026. No sequence similarity was found with
      any known bacterial lipases/esterases; instead, the most similar enzymes were
      several filamentous fungal lipases. Although the similarity was very low (less
      than 16%), there were many conserved regions over the entire sequence and N
      terminal oxyanion hole (RG) region, a signature sequence of filamentous fungal
      lipases. The novel protein M37 was produced in both a soluble and insoluble form
      when the Escherichia coli cells harboring the gene were cultured at 18 degrees C.
      The soluble protein exhibited lipase activity in a pH-stat assay using an olive
      oil emulsion. The M37 lipase also displayed a maximum activity at 25 degrees C
      and maintained its activity at a low temperature range (5-25 degrees C) with an
      activation energy (E(a)) of 2.07 kcal/mol. Accordingly, these results indicate
      that the M37 lipase from P. lipolyticum sp. nov. is a new cold-adapted enzyme.

PMID- 16088347
TI  - A membrane bioreactor for the biotransformation of alpha-pinene oxide to
      isonovalal by Pseudomonas fluorescens NCIMB 11671.
AB  - In this work the biotransformation of alpha-pinene oxide to isonovalal using
      resting cells of Pseudomonas fluorescens NCIMB 11671 was evaluated in a membrane
      bioreactor for biotransformations (MBB). Since the membrane area required to
      obtain optimum productivities was calculated to be very large (1,000 m2 m(-3)),
      and not possible to fit into the laboratory reactor used, we initially evaluated
      performance with lower membrane areas (71 m2 m(-3)) in a batch system with both
      the substrate and product in the organic phase. This resulted in low
      productivities due to mass transfer limitations, so an optimum feeding rate of
      0.1 g alpha-pinene oxide h(-1) g(cells) (-1) added directly to the reactor
      contents was determined in batch culture to minimise inhibition. The MBB was then
      operated continuously for the production of isonovalal, and a final concentration
      of 108 g l(-1) was obtained in the organic reservoir after nearly 400 h of
      operation (0.32 g-isonovalal l(-1) h(-1)), and the reaction was found not to be
      mass transfer limited. Finally, the relative viability of the cells was measured
      using fluorescent probes, and their half-life was found to be almost 2 months,
      confirming the ability of the MBB to facilitate biotransformations with
      inhibitory substrates and products.

PMID- 16088348
TI  - The sequence upstream of the -10 consensus sequence modulates the strength and
      induction time of stationary-phase promoters in Escherichia coli.
AB  - We constructed a library of synthetic stationary-phase promoters for Escherichia
      coli. For designing the promoters, the known -10 consensus sequence, as well as
      the extended -10 region, and an A/T-rich region downstream of the -10 region were
      kept constant, whereas sequences from -37 to -14 were partially or completely
      randomised. For detection and selection of stationary-phase promoters, green
      fluorescent protein (GFP) with enhanced fluorescence was used. To establish the
      library, 33 promoters were selected, which differ in strength from 670 to more
      than 13,000 specific fluorescence units, indicating that the strength of
      promoters can be modulated by the sequence upstream of the -10 region. DNA
      sequencing revealed a preferential insertion of nucleotides depending on the
      position. By expressing the promoters in an rpoS-deficient strain, a special
      group of stationary-phase promoters was identified, which were expressed
      exclusively or preferentially by RNA polymerase holoenzyme Esigma(s). The DNA
      sequence of these promoters differed significantly in the region from -25 to -16.
      Furthermore, it was shown that the DNA curvature of the promoter region had no
      effect on promoter strength. The broad range of promoter activities make these
      promoters very suitable for fine-tuning of gene expression and for cost-effective
      large-scale applications in industrial bioprocesses.

PMID- 16088349
TI  - 10 years of the nisin-controlled gene expression system (NICE) in Lactococcus
      lactis.
AB  - Lactococcus lactis is a Gram-positive lactic acid bacterium that, in addition to
      its traditional use in food fermentations, is increasingly used in modern
      biotechnological applications. In the last 25 years great progress has been made
      in the development of genetic engineering tools and the molecular
      characterization of this species. A new versatile and tightly controlled gene
      expression system, based on the auto-regulation mechanism of the bacteriocin
      nisin, was developed 10 years ago-the NIsin Controlled gene Expression system,
      called NICE. This system has become one of the most successful and widely used
      tools for regulated gene expression in Gram-positive bacteria. The review
      describes, after a brief introduction of the host bacterium L. lactis, the
      fundaments, components and function of the NICE system. Furthermore, an extensive
      overview is provided of the different applications in lactococci and other Gram
      positive bacteria: (1) over-expression of homologous and heterologous genes for
      functional studies and to obtain large quantities of specific gene products, (2)
      metabolic engineering, (3) expression of prokaryotic and eukaryotic membrane
      proteins, (4) protein secretion and anchoring in the cell envelope, (5)
      expression of genes with toxic products and analysis of essential genes and (6)
      large-scale applications. Finally, an overview is given of growth and induction
      conditions for lab-scale and industrial-scale applications.

PMID- 16088350
TI  - Purification of His6-organophosphate hydrolase using monolithic supermacroporous
      polyacrylamide cryogels developed for immobilized metal affinity chromatography.
AB  - Organophosphate hydrolase containing hexahistidine tag at the N-terminus of
      recombinant protein (His6-OPH) and expressed in Escherichia coli cells was
      purified using supermacroporous polyacrylamide-based monolith columns with
      immobilized metal affinity matrices [Me2+-iminodiacetic acid (IDA)-polyacrylamide
      cryogel (PAA) and Me2+-N,N,N'-tris (carboxymethyl) ethylendiamine (TED)-PAA].
      Enzyme preparation with 50% purity was obtained by direct chromatography of
      nonclarified cell homogenate, whereas the combination of addition of 10 mM
      imidazole to buffers for cell sonication and sample loading, the use of precolumn
      with IDA-PAA matrix noncharged with metal ions, and the application of high flow
      rate provided the 99% purity of enzyme isolated directly from crude cell
      homogenate. Co2+-IDA-PAA provided the highest level of selectivity for His6-OPH.
      Comparative analysis of purification using Co2+-IDA-PAA and Ni-nitrilotriacetic
      acid-agarose showed obvious advantages of the former in process time, specific
      activity of purified enzyme, and simplicity of adsorbent regeneration.

PMID- 16088351
TI  - Biological activity of Bifidobacterium longum in response to environmental pH.
AB  - The influence of environmental pH on biological activity of Bifidobacterium
      longum CRL 849 grown in MRS-raffinose was evaluated. At pH 6.0, 5.5 and 5.0,
      raffinose was completely consumed by this microorganism, showing different
      consumption rates at each pH value (between 3.03 and 0.76 mmol l(-1) h(-1)). At
      pH 4.5, the growth was lowest. The removal of raffinose was due to the alpha
      galactosidase (alpha-gal) activity of this bifidobacteria, which was highest at
      pH 6.0-5.5 (1,280-1,223 mU ml(-1)). The production of beta-glucosidase (beta-glu)
      showed a similar pattern to alpha-gal activity with major values. The yield of
      organic acids produced during raffinose consumption was also highest at pH 6.0
      5.5. The results of this study will allow the selection of the optimum growth
      conditions of B. longum CRL 849, with elevated levels of alpha-gal to be used in
      the reduction of nondigestible alpha-oligosaccharide in soy products and beta-glu
      activities involved in isoflavone conversion to bioactive forms when used as
      starter culture.

PMID- 16088352
TI  - Salt-regulated mannitol metabolism in algae.
AB  - Mannitol, one of the most widely occurring sugar alcohol compounds, is found in
      bacteria, fungi, algae, and plants. In these organisms the compound acts as a
      compatible solute and has multiple functions, including osmoregulation, storage,
      and regeneration of reducing power, and scavenging of active oxygen species.
      Because of the diverse functions of mannitol, introducing the ability to
      accumulate it has been a hallmark of attempts to generate highly salt-tolerant
      transgenic plants. However, transgenic plants have not yet improved significantly
      in their salt tolerance. Recently, we purified and characterized 2 enzymes that
      biosynthesize mannitol, mannitol-1-phosphate dehydrogenase (M1PDH) and mannitol-1
      phosphate-specific phosphatase, from the marine red alga Caloglossa continua,
      which grows in estuarine areas where tide levels fluctuate frequently. The
      activation of Caloglossa M1PDH is unique in that it is regulated by salt
      concentration at enzyme level. In this review we focus on the metabolism of
      mannitol, mainly in marine photosynthetic organisms, and suggest how this might
      be applied to producing salt-tolerant transgenic plants.

PMID- 16088353
TI  - Organization of the mitochondrial genome of mantis shrimp Pseudosquilla ciliata
      (Crustacea: Stomatopoda).
AB  - We determined the nearly complete mitochondrial genome of Pseudosquilla ciliata
      (Crustacea, Stomatopoda), including all protein-coding genes and all but one of
      the transfer RNAs. There were no gene rearrangements relative to the pattern
      shared by crustaceans and hexapods. Phylogenetic analysis using concatenated
      amino acid sequences of the mitochondrial protein-coding genes confirmed a basal
      position of Stomatopoda among Eumalacostraca. Pancrustacean relationships based
      on mitogenomic data were analyzed and are discussed in relation to crustacean and
      hexapod monophyly and hexapod affinities to crustacean subtaxa.

PMID- 16088354
TI  - Three types of acidic polysaccharides associated with coccolith of Pleurochrysis
      haptonemofera: comparison with Pleurochrysis carterae and analysis using
      fluorescein-isothiocyanate-labeled lectins.
AB  - In the coccolithophorid microalgae acidic polysaccharides are considered to be
      involved in the formation of the calcified scale, coccolith. Characteristics of
      the acidic polysaccharides extracted from the cell surface of the
      coccolithophorid Pleurochrysis haptonemofera were analyzed. The acidic
      polysaccharides on the cell surface can be detected by measuring fluorescence of
      cells after fluorescein-isothiocyanate-labeled lectin staining by flow cytometry.
      Flow cytometric analyses revealed that the acidic polysaccharides remained on the
      cell surface even after CaCO3 in the coccolith was dissolved by lowering pH, but
      they were extracted by subsequent EDTA or EGTA treatment, suggesting that they
      are bound not into the CaCO3 crystals of the coccolith, but onto the surface via
      Ca2+. Analyses of the acidic polysaccharides by anion exchange chromatography,
      colloidal precipitation with divalent cations, and polyacrylamide gel
      electrophoresis (PAGE) revealed that P. haptonemofera has 3 types of acidic
      polysaccharides (Ph-PS-l, -2, and -3). The PAGE patterns suggested that Ph-PS-2
      has a repeated structure with a broad range of molecular weight, as in
      Pleurochrysis carterae, while Ph-PS-1 and -3 contain several minor components in
      addition to a major component, respectively. The minor components in Ph-PS-1 and 
      3 that have not been found in P. carterae might be characteristic of P.
      haptonemofera. Analyses of both the cell surface treated by various
      concentrations of EDTA and EGTA and the extracts suggested that Ph-PS-2, which is
      distinguishable by a higher affinity to concanavalin A, is bound onto the
      coccolith surface more intensely than the other two types of acidic
      polysaccharides.

PMID- 16088355
TI  - Segregation of microsatellite alleles in gynogenetic diploid Pacific abalone
      (Haliotis discus hannai).
AB  - Inheritance of 9 microsatellite loci was examined in 3 families of gynogenetic
      Pacific abalone Haliotis discus hannai produced by fertilizing eggs with UV
      irradiated sperm followed by inhibition of the second meiotic division. The
      proportion of heterozygous progeny was used to estimate marker-centromere (M-C)
      distances. All loci conformed to Mendelian segregation in the control crosses
      when null alleles were accounted for. The absence of paternal alleles confirmed
      the gynogenetic origin of the offspring and indicated 100% success for 3
      families. Estimated recombinant frequencies ranged from 0.10 to 0.60, which is
      lower than those observed in other gynogenetic diploid animals. The mean
      recombination frequency was 0.22, corresponding to a fixation index of 0.78 in
      one generation. This is 3.12 times the increase in homozygosity expected after
      one generation of sib mating (0.25), suggesting meiotic gynogenesis may be an
      effective means of rapid inbreeding in the abalone. M-C map distances for the 9
      loci varied between 5 and 30 cM under the assumption of complete interference.
      The information about M-C distances will be useful for future gene mapping in H.
      discus hannai.

PMID- 16088356
TI  - Bacterial endosymbioses of gutless tube-dwelling worms in nonhydrothermal vent
      habitats.
AB  - Gutless tube-dwelling worms of pogonophorans (also known as frenulates) and
      vestimentiferans depend on primary production of endosymbiotic bacteria. The
      endosymbionts include thiotrophs that oxidize sulfur for autotrophic production
      and methanotrophs that oxidize and assimilate methane. Although most of the
      pogonophoran and vestimentiferan tube worms possess single thiotrophic 16S rRNA
      genes (16S rDNA) related to gamma-proteobacteria, some pogonohorans are known to
      bear single methanotroph species or even dual symbionts of thiotrophs and
      methanotrophs. The vestimentiferan Lamellibrachia sp. L1 shows symbiotic 16S rDNA
      sequences of alpha-, beta-, gamma-, and epsilon-proteobacteria, varying among
      specimens, with RuBisCO form II gene (cbbM) sequences related to beta
      proteobacteria. An unidentified pogonophoran from the world's deepest cold seep,
      7326-m deep in the Japan Trench, hosts a symbiotic thiotroph based on 16S rDNA
      with the RuBisCO form I gene (cbbL). In contrast, a shallow-water pogonophoran
      (Oligobrachia mashikoi) in coastal Japan Sea has a methanotrophic 16S rDNA and
      thiotrophic cbbL, which may suggest the feature of type X methanotrophs. These
      observations demonstrate that pogonophoran and vestimentiferan worms have higher
      plasticity in bacterial symbioses than previously suspected.

PMID- 16088357
TI  - Infection control in a hernia clinic: 24 year results of aseptic and antiseptic
      measure implementation in 4,620 "clean cases".
AB  - Post Mesh Herniorrhaphy Infection [PMHI] occurs between 3 to 4% of inguinal and 8
      to 14% of ventral herniorrhaphies producing an unacceptably high morbidity.
      Before opening a Hernia Clinic, our infection rate was around 5% for "clean"
      inguinals and 8% for "clean" ventral herniorrhaphies. Starting in 1982 we
      implemented a stricter operative aseptic protocol plus the per-operative
      administration of 1 g of intravenous Cefazolin. In addition, wounds were
      irrigated with a solution containing 80 mgs of Gentamycin Sulphate dissolved in
      250 ml of Normal Saline Solution. During a period of 25 years these measures were
      used in 4300 consecutive "clean "Inguinal and 320 "clean" Ventral
      herniorrhaphies. Since the implementation of the above-mentioned aseptic and
      antiseptic steps no further wound infections were encountered. In our hands, the
      combination of rigorous aseptic operating room routine plus intravenous and
      topical antibiotics have, up to now, effectively eliminated wound infections in
      "clean" herniorrhaphy cases.

PMID- 16088358
TI  - Early results of a randomised trial comparing Prolene and VyproII-mesh in
      endoscopic extraperitoneal inguinal hernia repair (TEP) of recurrent unilateral
      hernias.
AB  - The purpose of this study was to compare a lightweight mesh to a standard
      polypropylene hernia mesh in endoscopic extraperitoneal hernioplasty in recurrent
      hernias. A total of 140 men with recurrent unilateral inguinal hernias were
      randomised to a totally extraperitoneal endoscopic hernioplasty (TEP) with
      Prolene or VyproII in a single-blinded multi-center trial. The randomisation and
      all data handling were performed through the Internet. 137 patients were operated
      as allocated. Follow-up was completed in 88% of the patients. The median
      operation times were 55 (24-125) min and 53.5 (21-123) min for the Prolene and
      VyproII groups, respectively. The meshes had comparable results in the surgeon's
      assessment of the handling of the mesh, return to work, return to daily
      activities, complications, postoperative pain and quality of life during the
      first 8 weeks of rehabilitation, except in General Health (GH) SF-36, where the
      VyproII-group had a significantly better score (P=0.045). The use of Prolene and
      VyproII-meshes in endoscopic repair of recurrent inguinal hernia seems to result
      in similar short-term outcomes and quality of life.

PMID- 16088359
TI  - A phenomenological theory of the isotropic to chiral smectic-C phase transition.
AB  - In this paper we discuss the direct isotropic to chiral smectic-C phase
      transition on the basis of a phenomenological theory. The model free energy is
      written in terms of the coupled order parameters including the spontaneous
      polarization. We present a detailed analysis of the different phases that can
      occur and analyze the question under which conditions a direct isotropic to
      chiral smectic-C phase transition is possible when compared to other phase
      transitions. On the basis of this model the isotropic-smectic-C* transition is
      always of first order. The theoretical predictions are compared with the
      available experimental results.

PMID- 16088360
TI  - Comparison of mineral quality and quantity in iliac crest biopsies from high- and
      low-turnover osteoporosis: an FT-IR microspectroscopic investigation.
AB  - Fourier-transform infrared microspectroscopy (FTIRM) allows analysis of mineral
      content, mineral crystal maturity and mineral composition at approximately 10
      micron spatial resolution. Previous FTIRM analyses comparing 4-micron thick
      sections from non-decalcified iliac crest biopsies from women with post
      menopausal osteoporosis, as contrasted with iliac crest tissue from individuals
      without evidence of metabolic bone disease, demonstrated significant differences
      in average mineral content (decreased in osteoporosis) and mineral crystal
      size/perfection (increased in osteoporosis). More importantly, these parameters,
      which vary throughout the tissue in relation to the tissue age in healthy bone,
      showed no such variation in bone biopsies from patients with osteoporosis. The
      present study compares the spatial and temporal variation in mineral quantity and
      properties in trabecular bone in high- and low-turnover osteoporosis.
      Specifically, six biopsies from women (n=5) and one man with high-turnover
      osteoporosis (age range 39-77) and four women and two men with low turnover
      osteoporosis (age range 37-63) were compared to ten "normal" biopsies from three
      men and seven woman (age range: 27-69). "High turnover" was defined as the
      presence of increased resorptive surface, higher than normal numbers of
      osteoclasts and greater than or equal to normal osteoblastic activity. "Low
      turnover" was defined as lower than normal resorptive surface, decreased
      osteoclast number and less than normal osteoblastic activity. Comparing
      variations in FTIR-derived values for each of the parameters measured at the
      surfaces of the trabecular bone to the maximum value observed in multiple
      trabeculae from each person, the high-turnover samples showed little change in
      the mineral: matrix ratio, carbonate: amide I ratio, crystallinity and acid
      phosphate content. The low-turnover samples also showed little change in these
      parameters, but in contrast to the high-turnover samples, the low-turnover
      samples showed a slight increase in these parameters, indicative of retarded, but
      existent resorption and formation. These data indicate that FTIR
      microspectroscopy can provide quantitative information on mineral changes in
      osteoporosis that are consistent with proposed mechanisms of bone loss.

PMID- 16088361
TI  - Serum insulin-like growth factor binding protein-1 levels and bone mineral
      density in older adults: the Rancho Bernardo Study.
AB  - Insulin-like growth factor-I (IGF-I) stimulates osteoblast function, inhibits
      collagen matrix degradation, and is positively associated with bone mineral
      density in most but not all studies. We previously reported that IGF-I was
      positively associated with BMD at the spine and hip in women but not men. Insulin
      like growth factor binding protein-1 (IGFBP-1), a potent modulator of IGF-I, is
      expressed in normal osteoblasts and inhibits collagen gene expression in bone,
      but little is known about the relationship between IGFBP-1 and bone mineral
      density (BMD). We report a cross-sectional study of serum IGFBP-1 levels and BMD
      in 1,139 community-dwelling men and postmenopausal women (not using estrogen),
      aged 44-98. In both sexes, IGFBP-1 levels increased linearly with age (p<0.001)
      and decreased with body mass index (BMI) quartile (p<0.001). After adjusting for
      age and BMI, there was no significant association between IGFBP-1 and BMD at the
      hip or spine. IGF-I and IGFBP-1 were weakly and inversely associated with each
      other. These findings suggest that if there is an important role for IGFBP-1 in
      bone metabolism, it is mediated or confounded by weight. Studies are needed to
      further investigate the relationship between inhibitory components of IGF-1 and
      bone loss.

PMID- 16088362
TI  - Risk factors for fracture of the shafts of the tibia and fibula in older
      individuals.
AB  - A case-control study to identify risk factors for fracture of the shafts of the
      tibia and fibula among persons 45 years of age and older was undertaken in five
      Northern California Kaiser Permanente Medical Centers during 1996-2001. One
      hundred seventy-nine cases of newly diagnosed fracture of the tibia/fibula shaft
      and 2,399 controls sampled from the membership lists of the same five medical
      centers were included. Information on potential risk factors was obtained by a
      standardized questionnaire administered by trained interviewers. The number of
      previous fractures was associated with an increased risk [adjusted odds ratio
      (OR) (95% confidence interval)=1.49 (1.09-2.03) per previous fracture].
      Attributes known or thought to be associated with protection against loss of bone
      mass, including high body mass index [adjusted OR=0.82 (0.69-0.97) per 5 kg/m2
      increase], having ever used thiazide diuretics or water pills for at least 1 year
      [adjusted OR=0.62 (0.38-1.02)], and current use of menopausal hormone therapy
      among females [adjusted OR=0.84 (0.53-1.32)] tended to show decreased risks.
      Factors generally associated with lower bone mass, such as current cigarette
      smoking [OR=1.55 (1.01-2.39)] and, to some extent, lack of physical activity
      [OR=1.31 (0.87-1.96) for the lowest quartile compared to the upper three
      quartiles], tended to demonstrate increased risks. The number of falls in the
      past year and risk factors for falls were not associated with tibia/fibula shaft
      fractures, and indicators of health status were weakly and inconsistently
      associated with risk. Thus, this study suggests that risk factors for low bone
      mass, but not health status or risk factors for falls, may be important in the
      etiology of fracture of the shaft of the tibia/fibula in older individuals.

PMID- 16088363
TI  - Short-term reduction in bone markers with high-dose simvastatin.
AB  - The effect of statins on bone mass and fracture rates is uncertain. Therefore, we
      investigated whether statin therapy acutely altered bone turnover as measured by
      changes in bone serum markers (bone-specific alkaline phosphatase, osteocalcin,
      and type I collagen N-telopeptide cross-links). Fasting blood samples were
      obtained from 55 (M/F 39/16) healthy nonsmoking adults (mean +/- standard
      deviation: age, 50.4+/-7.5 years; body mass index, 27.8+/-4.9 kg/m(2)) with low
      density lipoprotein cholesterol concentrations between 3.38-4.90 mmol/l. Subjects
      were randomized to four possible 8-week treatment regimens: placebo (n =14),
      pravastatin 40 mg/daily (n =12), simvastatin 20 mg/daily (n =14) or simvastatin
      80 mg/daily (n =15). High-dose simvastatin (80 mg/daily) produced a significant
      reduction in bone-specific alkaline phosphatase as compared with other treatment
      regimens (p =0.009). However, there were no changes in urinary N-telopeptide
      cross-links, a sensitive marker of bone resorption. Short-term use of high-dose
      simvastatin lowers the level of the serum bone marker bone-specific alkaline
      phosphatase, which suggests the possibility of reduced bone turnover.

PMID- 16088364
TI  - Factors associated with prenatal smoking among black women in eastern North
      Carolina.
AB  - OBJECTIVES: The objective of this research was to explore prenatal smoking
      behaviors among Black women attending prenatal clinics. Despite the racial
      disparities in poor pregnancy outcomes, and the well-known association of smoking
      with harmful outcomes, little research has been conducted about prenatal smoking
      among Black women. METHODS: Women were enrolled in the study and interviewed at
      the time of the first prenatal visit. The interview contained items to assess
      prenatal smoking and cessation, depressive symptoms, demographic factors, and
      beliefs about smoking. Reports of smoking cessation were verified using urinary
      cotinine. RESULTS: The sample consisted of 811 Black women. Fourteen percent of
      the women were self-reported smokers, 12.6% reported cessation and 73% were
      nonsmokers. Twenty percent of the self-reported quitters had elevated cotinine;
      when these women were reclassified, 17% of the women were smokers. Factors
      associated with smoking in logistic regression analysis included elevated
      maternal depressive symptoms (OR = 1.7, 95% CI: 1.1-2.6), maternal age 20 years
      or older (OR = 1.94; 95% CI: 1.1, 3.3), less than a high school education (OR =
      2.2; 95% CI: 1.2, 3.8), unmarried/not living with a partner (OR = 1.9; 95% CI:
      1.0, 3.6), and allowing smoking in the home (OR = 5.5; 95% CI: 3.4, 8.6).
      CONCLUSIONS: The prevalence of maternal prenatal smoking was much higher among
      women in this sample than has been previously reported. The rate of nondisclosure
      of smoking among self-reported quitters was also high. Maternal behavioral
      (allowing smoking in the home) and psychosocial factors (depressive symptoms)
      were associated with prenatal smoking.

PMID- 16088365
TI  - Variations in patterns of highly active antiretroviral therapy (HAART) adherence.
AB  - Strict adherence to highly active antiretroviral therapy (HAART) is necessary for
      successful suppression of HIV replication. A large number of individuals are not
      adherent, however, and the reasons for non-adherence are varied and complex. We
      utilized cluster analyses to identify subgroups of adherers in a sample of 222
      HIV positive individuals whose HAART use was electronically monitored. Five
      distinct subgroups were identified, with characteristic variations across the
      week and over the course of the 4-week study. Additional comparisons of
      demographic and behavioral variables found the worst adherers to have higher
      rates of substance use, and that a group with higher rates of cognitive
      impairment had a consistent drop in adherence during the weekends. In addition,
      the group with the best adherence had more individuals over the age of 50 years.
      The results of the current study indicate that distinct subgroups of adherers may
      exist, and suggest that interventions designed to improve adherence can be
      designed to accommodate this variability in behavior.

PMID- 16088366
TI  - Changes in willingness to participate in HIV vaccine trials among HIV-negative
      injection drug users.
AB  - Injection drug users (IDUs) represent an important risk group for HIV infection.
      We assessed correlates of IDUs' willingness to participate (WTP) in HIV vaccine
      trials, and examined temporal changes in WTP. Participants were enrolled in
      ALIVE, a prospective study of HIV among IDUs in Baltimore; semi-annual visits
      include interviews and HIV serology. Questionnaires regarding WTP were
      administered in 1993-1994 and again in 2001-2002. Logistic regression was
      conducted to identify correlates of WTP. Wave 1 of the survey included 440
      participants; Wave 2 included 582 participants (189 participated in both waves).
      WTP increased modestly over time (83.4 vs. 86.3%; p = 0.16). Monetary incentives
      were the strongest predictor of WTP (adjOR = 2.73; 95% CI: 1.72-4.35). High
      expectations of HIV treatment effectiveness did not predict WTP. In this cohort,
      WTP remained strong and modestly increased over the study period. These results
      should be considered in the planning of sampling and retention strategies for
      future vaccine trials.

PMID- 16088367
TI  - Predictors of serostatus disclosure to partners among young people living with
      HIV in the pre- and post-HAART eras.
AB  - Predictors of serostatus disclosure were identified among youth living with HIV
      pre- and post-introduction of highly active antiretroviral therapy (HAART). Two
      cohorts of HIV-positive youth, aged 13-24, in 1994-1996 (n = 351) and 1999-2000
      (n = 253) in Los Angeles, New York, San Francisco, and Miami were sampled through
      medical providers and a variety of social service agencies. Data were collected
      on demographic, social, medical, and behavioral topics. Men who had sex with men
      were more likely to disclose serostatus to their partners. Moreover, a positive
      association with length of time since diagnosis and the likelihood of disclosure
      exists; across time, youth were less likely to disclose serostatus to casual
      partners or HIV-negative partners. Post-HAART, number of sex acts with a partner
      was associated with increased likelihood of disclosure. Interventions for HIV
      positive youth must improve disclosure to casual and serodiscordant sexual
      partners.

PMID- 16088368
TI  - Changes in attitudes toward antiviral medication: a comparison of women living
      with HIV/AIDS in the pre-HAART and HAART Eras.
AB  - To examine potential changes in attitudes toward antiviral medication since the
      advent of highly active antiretroviral therapy (HAART), focused interviews were
      conducted with two samples of women living with HIV/AIDS; one in the pre-HAART
      era (1994-1996) and a second matched sample in the HAART era (2000-2003). Women
      in the pre-HAART era held highly negative attitudes toward antiviral medications,
      perceived them as ineffective with few benefits and viewed side effects as
      intolerable. In contrast, women in the HAART era were less likely to report
      negative attitudes, which were balanced by more frequent reports of perceived
      benefits and more likely to view side effects as temporary and manageable.
      African American women in both eras were more likely to hold negative attitudes
      and less likely to perceive benefits than White and Puerto Rican women. These
      findings suggest that views of antiviral medication have improved since the
      advent of HAART, but that negative attitudes and side-effect concerns remain
      which should be addressed in interventions to promote treatment acceptance and
      adherence.

PMID- 16088369
TI  - Housing status and HIV risk behaviors: implications for prevention and policy.
AB  - This paper examines housing as a contextual factor affecting drug and sexual risk
      behaviors among HIV positive people using pooled interview data from 2149 clients
      presenting for services at 16 medical and social service agencies participating
      in a multi-site evaluation study. The odds of recent drug use, needle use or sex
      exchange at the baseline interview was 2-4 times as high among the homeless and
      unstably housed compared to persons with stable housing. Follow-up data collected
      6-9 months after baseline showed that change in housing status was associated
      with change in risk behaviors. Persons whose housing status improved between
      baseline and follow-up significantly reduced their risks of drug use, needle use,
      needle sharing and unprotected sex by half in comparison to individuals whose
      housing status did not change. In addition, for clients whose housing status
      worsened between baseline and follow-up, their odds of recently exchanging sex
      was over five times higher than for clients whose housing status did not change.
      The provision of housing is a promising structural intervention to reduce the
      spread of HIV.

PMID- 16088370
TI  - Social and lifestyle determinants of depression, anxiety, sleeping disorders and
      self-evaluated quality of life in Russia--a population-based study in
      Arkhangelsk.
AB  - BACKGROUND: The paper investigates social and lifestyle determinants of
      depression, anxiety, sleeping disorders and self-evaluated low quality of life in
      a population sample from the northwest of Russia. METHODS: Altogether 1968 men
      and 1737 women aged 18-90 years participated in a population-based study in
      Arkhangelsk, Russia, in the period 1999-2000. Depression, anxiety, and sleeping
      disorders were evaluated by a questionnaire with the formulations that have been
      previously used in population studies in Northern Norway. Alcohol dependence was
      diagnosed by the Alcohol Use Disorders Identification Test (AUDIT). Quality of
      life was evaluated by a 10-score Cantril Ladder. A score lower than five was
      defined as low quality of life. Relations between depression, anxiety, and
      sleeping disorders and socioeconomic/lifestyle factors were tested by logistic
      regression analyses. RESULTS: Women reported significantly higher prevalence of
      depression, anxiety and/or sleeping disorders than men: 68.7% and 32.3%,
      respectively. Depression, anxiety, sleeping disorders and low quality of life
      were positively associated with self-evaluation of nutrition as "poor", low
      consumption of food, and with low-paid professional status. Depression and
      sleeping disorders were associated with smoking, hazardous level of alcohol
      drinking and alcohol dependence. Anxiety and low quality of life were associated
      with alcohol dependence. Depression, anxiety, sleeping disorders and low quality
      of life had a strong positive association with circulatory diseases and
      gastrointestinal diseases, the association remained significant after adjustment
      for smoking and alcohol variables. CONCLUSIONS: A considerable part of the
      examined Russian population experienced depression, anxiety, and sleeping
      disorders that were strongly positively associated with poor nutrition, low
      socioeconomic status and adverse health behaviors (alcohol use disorders,
      smoking).

PMID- 16088371
TI  - Violence and PTSD in Mexico: gender and regional differences.
AB  - OBJECTIVE: We examined the lifetime prevalence of violence in Mexico and how
      different characteristics of the violent event effect the probability of meeting
      criteria for lifetime post-traumatic stress disorder (PTSD). METHOD: We
      interviewed a probability sample of 2,509 adults from 4 cities in Mexico (Oaxaca,
      Guadalajara, Hermosillo, Merida) using the Composite International Diagnostic
      Interview (CIDI). RESULTS: Lifetime prevalence of violence was 34%. Men reported
      more single-experience, recurrent, physical, adolescent, adulthood, and stranger
      violence; women more sexual, childhood, family, and intimate partner violence.
      Prevalence was generally higher in Guadalajara, though the impact was greater in
      Oaxaca compared to other cities. Of those exposed, 11.5% met DSM-IV criteria for
      PTSD. Probabilities were highest after sexual and intimate partner violence,
      higher for women than men, and higher in Oaxaca than other cities. CONCLUSIONS:
      It is important to consider the characteristics and the context of violence in
      order to develop effective prevention and intervention programs to reduce the
      exposure to and impact of violence.

PMID- 16088372
TI  - The assessment of need for mental health services.
AB  - BACKGROUND: The field of psychiatric epidemiology has yielded several large and
      important studies of the prevalence of psychiatric disorders. These surveys have
      been enhanced by the inclusion of methodologies that reflect the needs for care
      of the population in question. Clinical studies of psychiatric disorders and
      unmet needs have focussed on identifying needs and correlating them with service
      evaluation and satisfaction measures. The association between prevalence, service
      use and unmet need requires review in order to establish whether there are trends
      and consistent findings. METHOD: Peer-reviewed studies involving the assessment
      of need up to the present were included. These were of two broad groups:
      population-based studies and clinical studies. Studies based on outcome measures,
      review articles, and child psychiatry, old age, and intellectual disability
      samples were excluded. We conducted a search of MEDLINE and PSYCHINFO using the
      key words, "mental health needs","assessment of need", and "needs assessment". In
      addition, we hand-searched key journals and sought personal communication with
      researchers in the field. RESULTS: A total of 14 population studies and 19
      clinical studies were retrieved. The percentage of the general population who
      reported at least one need for care ranged from 9.5% to 13.8%. The numbers of
      needs in psychiatric patients ranged from 3.3 to 8.6. Correlates of unmet need
      include: unemployment, single status, low quality of life and high disability
      scores, and the presence of certain psychiatric diagnoses, such as affective
      psychosis and personality disorders. Higher rates of met need and service
      satisfaction are correlated with a longer duration of service contact.
      CONCLUSION: The assessment of need to date has been established either by service
      use data to make inferences about unmet need, by asking limited guided questions
      about needs, or by using established needs assessment instruments. The high
      prevalence of psychiatric disorders and the weak correlation between disorder and
      unmet need require a combined approach towards service development.

PMID- 16088373
TI  - The process of care in residential facilities--a national survey in Italy.
AB  - BACKGROUND: Although residential facilities (RFs) have largely replaced mental
      hospitals (MHs) in most developed countries for the long-term residential care of
      severely impaired patients, the process of care in RFs has not been well studied.
      The aim of this paper is to investigate the process of care in 265 RFs,
      representing 19.3% of all RFs in Italy, and to devise a classification of RFs
      based on process characteristics. METHODS: Structured interviews were conducted
      with the manager and staff of each RF. Residents were evaluated using
      standardized rating instruments. RESULTS: Most RFs had specific admission
      criteria, with one third having a waiting list that averaged about 3 months.
      There was no formal limitation to the length of stay in three quarters of RFs,
      and turnover rates were very low. Although a homelike atmosphere was found in
      many RFs, most facilities had restrictive rules on patients' daily lives and
      behaviours. RFs carried out several external activities targeted at integrating
      patients within the local community. Standardized assessment instruments and
      written treatment plans were rarely used. A cluster analysis based on the levels
      of restrictiveness and the standardization of the process of care classified RFs
      into five groups that differed with respect to daily staff coverage, size,
      geographical distribution and proportion of former MH residents. No significant
      intercluster differences were associated with the current clinical and
      psychosocial characteristics of residents, or with several other outcome
      variables. CONCLUSIONS: This study provides naturalistic evidence of the
      heterogeneity of the process of residential care on a large scale. Future efforts
      should focus on developing an empirical classification of RFs, as well as on
      national and international standards of care and staffing to address patients'
      needs.

PMID- 16088374
TI  - Deprivation: different implications for forensic psychiatric need in urban and
      rural areas.
AB  - BACKGROUND: Ecological relationships between deprivation and forensic psychiatric
      admission rates may differ in urban and rural areas. AIMS: The aim of the study
      was to compare the relationship between material deprivation and forensic
      admission rates in rural and urban areas for a whole-national service in Ireland
      over a 3-year period. METHOD: All Irish forensic admissions from 1997 to 1999
      were allocated to the appropriate small area. Material deprivation scores were
      calculated from census data. Mean annual admission rates and Bayesian
      standardised forensic admission ratios for small areas were aggregated by
      material deprivation score and population density. RESULTS: At small area level,
      there were significant non-linear increases in forensic admissions with
      increasing deprivation. The increases in urban areas (population density
      >10/hectare) were absent in less densely populated areas. CONCLUSIONS:
      Deprivation alone may not be the key factor in predicting forensic service
      utilisation. Factors associated with specifically urban deprived areas may be of
      greater relevance in planning services.

PMID- 16088375
TI  - In ovo neuromuscular stimulation alters the skeletal muscle phenotype of the
      chick.
AB  - 4-aminopyridine (4-AP) is a drug that blocks the potassium channels in neurons
      and stimulates the release of the neurotransmitter acetylcholine (ACh), enhancing
      its availability at the synaptic cleft. The effects of 4-AP induced neuromuscular
      stimulation on skeletal muscle formation and development were investigated in
      embryonic chicks. Fertile white Leghorn eggs were incubated at 37.5 degrees C and
      windowed on day three of incubation. On embryonic days (E) 10, 11, 12 and 13 half
      of the eggs were injected with 100 microl of PBS buffer containing 0.2 microg 4
      AP and the control group was administered 100 microl of PBS only. 4-AP treated
      (T) embryos showed at least a 10% increase in mean body mass relative to the
      controls (C) (P<0.05) at ages E14, E15 and E16. Tibia and femur lengths in the 4
      AP treated embryos were significantly greater than the controls at E15 and E16
      (P<0.05). The 4-AP treated animals had a 36.8% greater number of myofibres than
      the control animals at E20. Nuclear number per cross sectional area in the M.
      Semitendinosus was significantly greater (P<0.01) at E16 in the treated compared
      to the control embryos. The 4-AP treated group exhibited a greater percentage
      area of oxidative fibres in cross sections of M. Semitendinosus than the control
      group at E16 (P<0.01) and at E20 (P<0.05). It may be concluded from these results
      that 4-AP induced neuromuscular stimulation has a significant effect on skeletal
      muscle characteristics, leg bone length and overall body mass.

PMID- 16088376
TI  - Myosin heavy chain composition and the economy of contraction in healthy and
      diseased human myocardium.
AB  - Changes in myosin heavy chain (MHC) isoform expression and protein composition
      occur during cardiac disease and it has been suggested that even a minor shift in
      MHC composition may exert a considerable effect on myocardial energetics and
      performance. Here an overview is provided of the cellular basis of the energy
      utilisation in cardiac tissue and novel data are presented concerning the economy
      of myocardial contraction in diseased atrial and ventricular human myocardium.
      ATP utilisation and force development were measured at various Ca(2+)
      concentrations during isometric contraction in chemically skinned atrial
      trabeculae from patients in sinus rhythm (SR) or with chronic atrial fibrillation
      (AF) and in ventricular muscle strips from non-failing donor or end-stage failing
      hearts. Contractile protein composition was analysed by one-dimensional gel
      electrophoresis. Atrial fibrillation was accompanied by a significant shift from
      the fast alpha-MHC isoform to the slow beta-MHC isoform, whereas both donor and
      failing ventricular tissue contained almost exclusively the beta-MHC isoform.
      Simultaneous measurements of force and ATP utilisation indicated that economy of
      contraction is preserved in atrial fibrillation and in end-stage human heart
      failure.

PMID- 16088377
TI  - The role of auxiliary dihydropyridine receptor subunits in muscle.
AB  - The skeletal muscle dihydropyridine receptor is a slowly-activating calcium
      channel that functions as the voltage sensor in excitation-contraction coupling.
      In addition to the pore-forming alpha(1S) subunit it contains the transmembrane
      alpha(2)delta-1 and gamma(1) subunits and the cytoplasmic beta(1a) subunit.
      Although the roles of the auxiliary subunits in calcium channel function have
      been intensively studied in heterologous expression systems, their functions in
      excitation-contraction coupling has only recently been elucidated in muscle cells
      of various null-mutant animal models. In this article we will briefly outline the
      current state of these investigations.

PMID- 16088378
TI  - Visual fields in flamingos: chick-feeding versus filter-feeding.
AB  - In birds, the position and extent of the region of binocular vision appears to be
      determined by feeding ecology. Of prime importance is the degree to which vision
      is used for the precise control of bill position when pecking or lunging at prey.
      In birds that do not require such precision (probe and filter-feeders), the bill
      falls outside the binocular field, which extends above and behind the head, thus
      providing comprehensive visual coverage. Flamingos Phoenicopteridae are highly
      specialised filter-feeders. They employ a unique technique that does not require
      accurate bill positioning in which the inverted head is placed between the feet.
      Feeding flamingos often walk forwards with the head pointing "backwards". Here we
      show that in Lesser Flamingos Phoeniconaias minor visual fields are in fact the
      same as those of birds that feed by precision pecking and that feeding flamingos
      are blind in the direction of their walking. We suggest that this is due to the
      requirement for accurate bill placement when flamingos feed their chicks with
      "crop-milk", and possibly when building their nest. We propose that chick-feeding
      may be the ultimate determinant of visual field topography in birds, not feeding
      ecology.

PMID- 16088380
TI  - Subcellular characterization of the primordial germ cell antigen PG2 in adult
      oocytes.
AB  - Primordial germ cells represent the founder population for establishing the germ
      line providing the continuity of life between generations. PG2, a germ cell
      specific antigen, is one of the few continuously detectable epitopes in mammalian
      primordial germ cells and it is dynamically expressed during early post
      fertilization development and during postnatal germ cell maturation.
      Immunoelectron microscopy shows a localization of PG2 in the peri-mitochondrial
      cytoplasm but its further subcellular or biochemical nature remains elusive. For
      further characterization of the PG2 epitope we used regular and semi-thin
      cryosection of ovulated and isolated follicular rabbit oocytes and localized all
      mitochondria with the help of the constitutive mitochondrial antigen MTC02 in
      double immunofluorescence stainings. Semi-thin cryosections of ovulated oocytes
      revealed a general close co-localization of both antibody reactions at the level
      of single mitochondria. In centrifuged follicular oocytes both antigens co
      sedimented almost completely indicating a topographical association of the
      epitopes on the basis of a strong interaction of PG2 with mitochondria. To begin
      to characterize the germ cell epitope biochemically we treated oocyte
      cryosections either with acetone to reduce lipids or with N-glycosidase F to
      remove N-linked glycosylations before the immuoreaction. Neither treatment
      affected the antibody characteristics, which suggests that the PG2 epitope is
      most probably a protein. Because of the close interaction of PG2 with the
      mitochondria we speculate that PG2 is involved in the change of the mitochondrial
      morphology typically observed during differentiation of germ cells.

PMID- 16088379
TI  - Expression of versican in relation to chondrogenesis-related extracellular matrix
      components in canine mammary tumors.
AB  - Versican plays a role in tumor cell proliferation and adhesion and may also
      regulate cell phenotype. Furthermore, it is one of the pivotal proteoglycans in
      mesenchymal condensation during prechondrogenesis. We have previously
      demonstrated accumulation of versican protein in myoepithelial-like spindle cell
      proliferations and myxoid tissues of complex and mixed mammary tumors of dogs.
      The objective of this study was to investigate whether the high expression of
      versican relates to prechondrogenesis in these tissues. Therefore, we aimed to
      identify cartilage markers, such as collagen type II and aggrecan both at mRNA
      and protein level in relation to versican. The neopitope of chondoitin-6-sulphate
      (3B3) known to be generated in developing cartilage has been investigated by
      immunohistochemisty and a panel of antibodies were used to characterize the
      phenotype of cells that are involved in cartilage formation. In addition, co
      localization of versican with hyaluronan and link protein was studied. RT-PCR
      revealed upregulation of genes of versican, collagen type II and aggrecan in
      neoplastic tissues, especially in complex and mixed tumors. Immunohistochemistry
      showed the expression of cartilage biomarkers not only in the cartilagenous
      tissues of mixed tumors, but also in myoepitheliomas and in the myoepithelial
      like cell proliferations and myxoid areas of complex and mixed tumors. The
      results show the cartilagenous differentiation of complex tumors and
      myoepitheliomas and indicate that the myxoid tissues and myoepithelial-like cell
      proliferations are the precursor tissues of the ectopic cartilage in mixed
      tumors. Furthermore, we suggest that cartilage formation in canine mammary tumors
      is a result of (myo)epithelial to mesenchymal transition.

PMID- 16088381
TI  - Programmed cell death and cell extrusion in rat duodenum: a study of expression
      and activation of caspase-3 in relation to C-jun phosphorylation, DNA
      fragmentation and apoptotic morphology.
AB  - The small intestinal epithelium is continuously renewed through a balance between
      cell division and cell loss. How this balance is achieved is uncertain. Thus, it
      is unknown to what extent programmed cell death (PCD) contributes to intestinal
      epithelial cell loss. We have used a battery of techniques detecting the events
      associated with PCD in order to better understand its role in the turnover of the
      intestinal epithelium, including modified double- and triple-staining techniques
      for simultaneously detecting multiple markers of PCD in individual cells. Only a
      partial correlation between TUNEL positivity for DNA fragmentation, c-jun
      phosphorylation on serine-63, positivity for activated caspase-3 and apoptotic
      morphology was observed. Our results show that DNA fragmentation does not
      invariably correlate to activation of caspase-3. Moreover, many cells were found
      to activate caspase-3 early in the process of extrusion, but did not acquire an
      apoptotic nuclear morphology until late during the extrusion process. These
      observations show that the lack of consensus between different methods for
      detecting PCD may be explained both by different timing of appearance of PCD
      markers and, additionally, by the occurrence of different forms of PCD during the
      normal turnover of cells on small intestinal villi.

PMID- 16088382
TI  - Immunochemical analysis of protein expression in breast epithelial cells
      transformed by estrogens and high linear energy transfer (LET) radiation.
AB  - Breast cancer is a complex disease involving numerous genetic aberrations.
      Immunochemical analysis of protein expression is presented in a human breast
      epithelial cell line neoplastically transformed by high linear energy transfer
      (LET) alpha particle radiation in the presence of 17beta estradiol (E) and in the
      parental human breast epithelial cell line (MCF-10F) which served as a non
      tumorigenic control. The aim of this work was to determine the levels of mRNA and
      protein expression in control and transformed cells at various stages of the
      neoplastic process. The levels of mRNA and protein expression of PCNA, c-fos,
      JNK2 and Fra-1 were increased in the transformed cell line compared to the levels
      in non-tumorigenic control cells. The transforming factor Rho A was significantly
      increased only in the tumor cell line. Furthermore, the levels of mRNA and
      protein expression of ErbB2 were significantly increased in the transformed cell
      line and in tumor cells derived from the transformed cells after injecting them
      into nude mice. A decrease in RbA/p48 protein expression and mRNA levels was
      observed in cells treated with double doses of alpha particle radiation in the
      presence of estrogen, regardless of tumorigenicity. Such expression was lower
      than that in the control untreated MCF-10F cells. In summary, these studies show
      that estrogen and high LET-radiation induce changes in oncoprotein expression and
      mRNA levels of human breast cell lines. These changes are indicative of a cascade
      of events that characterize the process of cell transformation in breast cancer.
      These results provide evidence that multiple steps with consecutive changes are
      involved when normal cells become tumorigenic cells as a result of alpha particle
      irradiation and estrogen treatments.

PMID- 16088383
TI  - Orientation of human semicircular canals measured by three-dimensional
      multiplanar CT reconstruction.
AB  - Analysis of vestibulo-ocular reflex experiments requires knowledge of the
      absolute orientations (with respect to skull landmarks) of semicircular canals
      (SCC). Data relating SCC orientations to accessible skull landmarks in humans are
      sparse, apart from a classic study of 10 skulls, which concluded that the
      horizontal and anterior SCC are not mutually orthogonal (111 +/- 7.6 degrees).
      Multiple studies of isolated labyrinths have shown the inter-SCC angles are close
      to 90 degrees. We hypothesized that a larger sample would yield mean absolute SCC
      orientations closer to the mutual orthogonality demonstrated for isolated
      labyrinths. We measured canal orientations with respect to accessible skull
      landmarks using 3-D multiplanar reconstructions of computerized tomography scans
      of the temporal bones of 22 human subjects. Images were acquired with 0.5-mm
      thickness and reconstructed with in-plane resolution of 234 microm. There was no
      significant difference between the left and a mirror image of the right (p > 0.57
      on multiway ANOVA of orientation vector coefficients), so data were pooled for
      the 44 labyrinths. The angle between the anterior and posterior SCC was 94.0 +/-
      4.0 degrees (mean +/- SD). The angle between the anterior and horizontal SCC was
      90.6 +/- 6.2 degrees. The angle between the horizontal and posterior SCC was 90.4
      +/- 4.9 degrees. The direction angles between a vector normal to the left
      horizontal SCC and the positive Reid's stereotaxic X (+nasal), Y (+left), and Z
      (+superior) axes were 108.7 +/- 7.5 degrees, 92.2 +/- 5.7 degrees, and 19.9 +/-
      7.0 degrees, respectively. The angles between a vector normal to the left
      anterior SCC and the positive Reid's stereotaxic X, Y, and Z axes were 125.9 +/-
      5.2 degrees, 38.4 +/- 5.1 degrees, and 100.1 +/- 6.2 degrees, respectively. The
      angles between a vector normal to the left posterior SCC and the positive Reid's
      stereotaxic X, Y, and Z axes were 133.6 +/- 5.3 degrees, 131.5 +/- 5.1 degrees,
      and 105.6 +/- 6.6 degrees, respectively. The mean anterior SCC-contralateral
      posterior SCC angle was 15.3 +/- 7.2 degrees. The absolute orientations of human
      SCC are more nearly orthogonal than previously reported.

PMID- 16088384
TI  - Planned delayed operation for barium extravasation into the peritoneal cavity.
AB  - BACKGROUND: Extravasation of barium into the peritoneal cavity occurs rarely but
      has lethal results. CASE: We describe a case of extravasation from the small
      bowel that was initially managed medically before a planned, delayed operation.
      We discuss the benefit/risk of delayed operation and reoperation.

PMID- 16088385
TI  - The identification of specialized pacemaking cells in the anal sphincters.
AB  - BACKGROUND AND AIMS: Interstitial cells of Cajal (ICC) are claimed to generate
      the electrical activity in the colon and stomach. As the external (EAS) and
      internal (IAS) anal sphincters exhibit resting electrical activity, we
      hypothesized the presence of ICC in these sphincters. This hypothesis was
      investigated in the current study. PATIENTS/METHODS: Specimens from the EAS and
      IAS were taken from normal areas of the anorectum which had been surgically
      excised by abdominoperineal operation for rectal cancer of 28 patients (16 men,
      12 women, mean age 42.2+/-4.8 years). The specimens were subjected to c-kit
      immunohistochemistry. Controls for the specificity of the antisera consisted of
      tissue incubation with normal rabbit serum substituted for the primary antiserum.
      RESULTS/FINDINGS: Fusiform, c-kit positive, ICC-like cells were detected in the
      anal sphincters; they had dendritic processes. They were clearly distinguishable
      from the non-branching, c-kit negative smooth and striated muscle cells of the
      anal sphincters. The specimens contained also c-kit positive mast cells, but they
      had a rounded body with no dendritic processes. Immunoreactivity was absent in
      negative controls in which the primary antibody was omitted.
      INTERPRETATION/CONCLUSION: We have identified, for the first time, cells in EAS
      and IAS with morphological and immunological phenotypes similar to ICCs of the
      gut. These cells appear to be responsible for initiating the slow waves recorded
      from the anal sphincters and for controlling their activity. A deficiency or
      absence of these cells may affect the anal motile activity. Studies are needed to
      explore the role of these cells in anal motility disorders.

PMID- 16088386
TI  - Bosentan, an endothelin receptor antagonist, reduces leucocyte adhesion and
      inflammation in a murine model of inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Endothelins, a group of polyfunctional cytokines, induce the
      adhesion of circulating leucocytes to venous endothelium, an initial step in the
      pathogenesis of a cellular infiltrate in inflammatory bowel disease (IBD). The
      effect of bosentan, a non-selective endothelin receptor antagonist, on leucocyte
      adhesion and inflammation in a murine model of IBD was studied. MATERIALS AND
      METHODS: Thirty BALB/c mice were divided into three groups of 10 animals:
      untreated controls, chronic colitis [dextran sodium sulphate (DSS), 3% w/v for 30
      days], and treatment with bosentan (30 mg/kg i.p. daily on days 26-30). On day
      30, adherent and rolling leucocytes and the average rolling velocity were
      assessed by intravital microscopy. Clinical and histological activity of
      inflammation were assessed by the disease activity index and modified Dieleman
      score, respectively. STATISTICS: Kruskal-Wallis test was used, followed by Dunn's
      method. A value of p<0.05 was considered significant. RESULTS: Compared to
      healthy controls, mice treated with DSS showed pronounced clinical and
      histological inflammation, and a higher number of rolling and adhering leucocytes
      in colonic submucosal venules. Therapy with bosentan significantly reduced
      clinical and histological inflammation. Adherent leucocyte levels were markedly
      lower (1.2+/-0.3 vs 23.7+/-2.8 adherent cells per 0.01 mm2, p<0.05). The number
      of rolling leucocytes was lower but not significantly different. However, rolling
      velocity was significantly higher (91.5+/-14.0 vs 19.0+/-1.6 microm/s, p<0.05).
      CONCLUSIONS: Bosentan reduces the adhesion of leucocytes in colonic submucosal
      venules and reduces inflammation in this mouse model of IBD. By inhibiting
      leucocyte adhesion, a crucial step in the recruitment of leucocytes to the
      inflamed tissue, bosentan is a potent therapeutic drug in this animal model.
      Further studies are necessary to investigate the role of bosentan as a novel drug
      in human IBD.

PMID- 16088387
TI  - Intraperitoneal instillation of polihexanide produces hypotension and
      vasodilation: in vivo and in vitro study in rats.
AB  - BACKGROUND AND AIMS: Treatment of peritonitis may include abdominal lavage with a
      local disinfectant polihexanide, available as 0.04% solution, which is often
      accompanied by hypotension. METHODS: We examined the effects of peritoneal
      installation of polihexanide or NaCl 0.9% (10 ml each, for 10 min; polihexanide
      n=5, NaCl n=5) on mean arterial pressure in healthy rats and, using intravital
      microscopy, measured in seven other animals the diameter of terminal ileum
      submucosal arterioles and venules before and after local superfusion with
      polihexanide. Furthermore, in an in vitro isometric preparation of rat thoracic
      aortal rings, with and without endothelium, we tested the effects of cumulative
      concentrations of polihexanide on vascular basic tension and on tension elicited
      by phenylephrine and KCl. RESULTS: It was found that polihexanide peritoneal
      instillation produced a decrease in mean arterial pressure, while superfusion
      with polihexanide caused local vasodilation of intestinal wall blood vessels. In
      vitro, polihexanide produced endothelium-dependent relaxation in the preparations
      pre-contracted with phenylephrine (EC(50), polihexanide 0.04% solution 2.53+/
      0.16 vs. 1.36+/-0.16, n=4, P<0.05; polihexanide 4.02+/-0.12 vs. 3.21+/-0.10,
      n=12, P<0.001;+ vs. - endothelium, respectively; -log g%) which (in aortae
      +endothelium) could be attenuated by either N(G)-nitro-L-arginine methyl ester, a
      nitric oxide generation inhibitor, or 1H-(1,2,4)oxodiazolo-(4,3-a)quinoxalin-1
      one, an inhibitor of guanylyl cyclase. The relaxing effect of polihexanide
      (aortae -endothelium) was not affected by K(+)-channel blocking agents
      charybdotoxin, tetraethylammoniumchloride, glibenclamide or 4-aminopyridine,
      while polihexanide had no effects on 40-mM KCl contractions. CONCLUSION: This
      implies that polihexanide may promote nitric oxide liberation, potassium channel
      activation and vasodilation that may result in hypotension.

PMID- 16088388
TI  - The effects of time, space and spectrum on auditory grouping in tungara frogs.
AB  - Male tungara frogs (Physalaemus pustulosus) produce complex calls consisting of
      two components, a approximately 350 ms FM sweep called the "whine" followed by up
      to seven approximately 40 ms harmonic bursts called "chucks". In order to choose
      and locate a calling male, females attending to choruses must group call
      components into auditory streams to correctly assign calls to their sources.
      Previously we showed that spatial cues play a limited role in grouping: calls
      with normal spectra and temporal structure are grouped over wide angular
      separations (< or =135 degrees ). In this study we again use phonotaxis to first
      test whether an alternative cue, the sequence of call components, plays a role in
      auditory grouping and second, whether grouping is mediated by peripheral or
      central mechanisms. We found that while grouping is not limited to the natural
      call sequence, it does vary with the relative onset times of the two calls. To
      test whether overlapping stimulation in the periphery is required for grouping,
      the whine and chuck were filtered to restrict their spectra to the sensitivity
      ranges of the amphibian and basilar papillae, respectively. For these dichotic
      like stimuli, grouping still occurred (albeit only to 45 degrees separation),
      suggesting that stream formation is mediated by central mechanisms.

PMID- 16088390
TI  - Dose-related steady states of fat loss in long-term leptin-treated ob/ob mice:
      leptin resistance or desensitization versus counterregulatory signaling.
AB  - We tried to unravel why leptin's fat store depleting action levels off in the
      course of long-term applications. Supplying leptin by minipump infusion for 2
      months to ob/ob mice at rates between 115 pmol day(-1) and 460 pmol day(-1)
      resulted in stable plasma leptin levels between 0.2 ng ml(-1) and 8 ng ml(-1).
      Initial treatment effects were leptin dose-dependent reductions in food intake
      and body mass, especially in fat content, followed by re-increases of food intake
      to levels only 4-18% below pre-treatment levels. Decreased body mass subsequently
      stabilized dose-dependently with body fat contents between 4% and 33% showing
      that total fat depletion was not a precondition for the progressive reduction of
      leptin-induced anorexia. Oxygen consumption measurements excluded contributions
      of enhanced energy dissipation to fat depletion. Plasma insulin concentrations
      declined from excessively high pre-treatment levels to steady, leptin dose
      dependent levels within the normal range. Temporary anorexia in response to
      repeated additional 1-day leptin injections (100 pmol g(-1) day(-1)) remained
      unchanged throughout long-term leptin infusion. Among various alternatives
      considered to explain the adipostatic equilibrium attained at new, dose-dependent
      levels under long-term leptin treatment, interaction between the leptin signal
      and at least one counteracting signal increasing with fat depletion is proposed
      as the most plausible working hypothesis.

PMID- 16088391
TI  - Torpor and thermal energetics in a tiny Australian vespertilionid, the little
      forest bat (Vespadelus vulturnus).
AB  - Data on thermal energetics for vespertilionid bats are under-represented in the
      literature relative to their abundance, as are data for bats of very small body
      mass. Therefore, we studied torpor use and thermal energetics in one of the
      smallest (4 g) Australian vespertilionids, Vespadelus vulturnus. We used open
      flow respirometry to quantify temporal patterns of torpor use, upper and lower
      critical temperatures (T (uc) and T (lc)) of the thermoneutral zone (TNZ), basal
      metabolic rate (BMR), resting metabolic rate (RMR), torpid metabolic rate (TMR),
      and wet thermal conductance (C (wet)) over a range of ambient temperatures (T
      (a)). We also measured body temperature (T (b)) during torpor and normothermia.
      Bats showed a high proclivity for torpor and typically aroused only for brief
      periods. The TNZ ranged from 27.6 degrees C to 33.3 degrees C. Within the TNZ T
      (b) was 33.3+/-0.4 degrees C and BMR was 1.02+/-0.29 ml O(2) g(-1) h(-1) (5.60+/
      1.65 mW g(-1)) at a mean body mass of 4.0+/-0.69 g, which is 55 % of that
      predicted for a 4 g bat. Minimum TMR of torpid bats was 0.014+/-0.006 ml O(2) g(
      1) h(-1) (0.079+/-0.032 mW g(-1)) at T (a)=4.6+/-0.4 degrees C and T (b)=7.5+/
      1.9. T (lc) and C (wet) of normothermic bats were both lower than that predicted
      for a 4 g bat, which indicates that V. vulturnus is adapted to minimising heat
      loss at low T (a). Our findings support the hypothesis that vespertilionid bats
      have evolved energy-conserving physiological traits, such as low BMR and
      proclivity for torpor.

PMID- 16088392
TI  - Cardiovascular responses of three salmonid species affected with amoebic gill
      disease (AGD).
AB  - The cardiovascular effects of amoebic gill disease (AGD) were investigated
      immediately following surgery in three salmonid species; Atlantic salmon (Salmo
      salar L.), brown trout (Salmo trutta L.) and rainbow trout (Oncorhynchus mykiss
      Walbaum). Fish, both naive (control) and infected (AGD-affected) of each species,
      were fitted with dorsal aorta catheters and cardiac flow probes. Cardiac output
      and dorsal aortic pressures were then continuously measured over a 6-h period
      following surgery. Results showed that Atlantic salmon, brown trout and rainbow
      trout displayed similar dorsal aortic pressure, cardiac output, and systemic
      vascular resistance (mean dorsal aotic pressure divided by cardiac output)
      values. However, the only significant differences relating to disease status i.e.
      infected or control, were found in Atlantic salmon. Although no significant
      differences were seen in dorsal aortic pressure values, AGD-affected salmon
      displayed significantly elevated systemic vascular resistance at 4 and 6 h post
      surgery. Cardiac output was also approximately 35% lower in AGD-affected salmon
      compared to the non-affected control counterparts. These results comparatively
      examine cardiac function in response to AGD across three salmonid species and
      highlight species-specific cardiovascular responses that occur in association
      with disease. It is suggested that the apparent cardiac dysfunction seen in AGD
      affected Atlantic salmon could, under stressful conditions, become exacerbated.
      Cardiac failure is therefore suggested to be a possible physiological mechanism
      by which AGD causes or contributes to mortality in Atlantic salmon.

PMID- 16088393
TI  - Wing morph-specific differences in the metabolism and endocrine control of
      reserve mobilization in adult males of a flightless bug, Pyrrhocoris apterus (L.)
      (Heteroptera).
AB  - The differences in the metabolism and endocrine control of reserve mobilization
      in long-winged (macropterous) and short-winged (brachypterous) males of a
      flightless firebug (Pyrrhocoris apterus) were studied. We found that protein
      content in the gut was significantly lower in 5-10 day-old macropterous males due
      to their fasting and higher in 28 day-old ones than in the same aged
      brachypterous counterparts as the result of renewed food intake. Overall protease
      activity was significantly lower in 10-14 day-old macropters, while an abrupt
      increase in the activity starting on day 21 after adult ecdysis was also
      associated with renewal of the food intake. The levels of carbohydrates in
      haemolymph were only slightly lower in 1-10 day-old macropterous males than in
      the same aged brachypters. However, more than twofold higher lipid content in
      haemolymph of 7-10 day-old macropterous males than in the same aged brachypterous
      males was found. Higher mobilization of lipid reserves from the fat bodies in
      macropterous males was accompanied by more intensive adipokinetic response and
      higher levels of adipokinetic hormone in the body. It is the first report of
      endocrine regulation of wing morph-related differences in the lipid mobilization
      in males of wing-polymorphic insects.

PMID- 16088394
TI  - Effects of spironolactone and RU486 on gene expression and cell proliferation
      after freshwater transfer in the euryhaline killifish.
AB  - We have explored the possible mechanisms by which mineralocorticoid (MR) and
      glucocorticoid (GR) receptors regulate the response to freshwater transfer in the
      gills of the euryhaline killifish Fundulus heteroclitus. Killifish were implanted
      with RU486 (GR antagonist) or spironolactone (MR antagonist) at doses of 0.1-1.0
      mg g(-1), and subsequently transferred from 10 per thousand brackish water to
      freshwater. Compared to brackish water sham fish, mRNA expression of CFTR and
      NKCC1 decreased in the gills of sham fish transferred to freshwater, whereas
      Na(+), K(+)-ATPase alpha(1a) mRNA expression and alpha protein abundance, as well
      as cell proliferation (detected using BrdU) increased. Spironolactone inhibited
      the normal increase in cell proliferation and Na(+), K(+)-ATPase expression after
      freshwater transfer. RU486 increased plasma cortisol levels and may have slightly
      inhibited Na(+), K(+)-ATPase activity, but did not change alpha(1a ) expression.
      RU486 had no effect on cell proliferation in the non-lamellar region of the
      gills, but increased proliferation in the lamellar region. Neither antagonist
      inhibited the suppression of CFTR or NKCC1 expression after freshwater transfer.
      Glucocorticoid receptor expression was reduced in all sham and antagonist
      treatments compared to untreated controls, but no other consistent differences
      were observed. The effects of spironolactone suggest that MR is important for
      regulating ion transport in killifish gills after freshwater transfer.

PMID- 16088395
TI  - Microsatellite and AFLP markers in the Prunus persica [L. (Batsch)]xP.
      ferganensis BC(1)linkage map: saturation and coverage improvement.
AB  - A set of 146 single sequence repeats (SSRs) and 14 amplified fragment length
      polymorphism (AFLP) primer combinations were used to enrich a previously
      developed linkage map obtained from a (Prunus persicaxP. ferganensis)xP. persica
      BC(1) progeny. Forty-one SSR primer pairs gave polymorphic patterns detecting 42
      loci. The restriction/selective primer AFLP combinations produced a total of 79
      segregating fragments. The resulting map is composed of 216 loci covering 665 cM
      with an average distance of 3.1 cM. Novel regions were covered by the newly
      mapped loci for a total of 159 cM. Eight linkage groups were assembled instead of
      the earlier 10 as two small groups (G1a and G8b), previously independent, were
      joined to their respective major groups (G1b and G8a). Several gaps were also
      reduced resulting in an improved saturation of the map. Twelve gaps >or=10 cm are
      still present. A comparative analysis against the Prunus reference map (71 anchor
      loci) pointed out an almost complete synteny and colinearity. Six loci were not
      syntenic and only two were not colinear. Genetic distances were significantly
      longer in our map than in the reference one.

PMID- 16088396
TI  - Comparative genetic maps reveal extreme crossover localization in the Aegilops
      speltoides chromosomes.
AB  - A total of 137 loci were mapped in Aegilops speltoides, the closest extant
      relative of the wheat B genome, using two F(2) mapping populations and a set of
      wheat-Ae. speltoides disomic addition (DA) lines. Comparisons of Ae. speltoides
      genetic maps with those of Triticum monococcum indicated that Ae. speltoides
      conserved the gross chromosome structure observed across the tribe Triticeae. A
      putative inversion involving the short arm of chromosome 2 was detected in Ae.
      speltoides. A translocation between chromosomes 2 and 6, present in the wheat B
      genome, was absent. The ligustica/aucheri spike dimorphism behaved as allelic
      variation at a single locus, which was mapped in the centromeric region of
      chromosome 3. The genetic length of each chromosome arm was about 50 cM,
      irrespective of its physical length. Compared to T. monococcum genetic maps,
      recombination was virtually eliminated from the proximal 50-100 cM and was
      localized in short distal regions, which were often expanded compared to the T.
      monococcum maps. The wheat B genome and the genome of Ae. longissima, a close
      relative of Ae. speltoides, do not show the extreme localization of crossovers
      observed in Ae. speltoides.

PMID- 16088397
TI  - A microsatellite-based, gene-rich linkage map for the AA genome of Arachis
      (Fabaceae).
AB  - Cultivated peanut (Arachis hypogaea) is an important crop, widely grown in
      tropical and subtropical regions of the world. It is highly susceptible to
      several biotic and abiotic stresses to which wild species are resistant. As a
      first step towards the introgression of these resistance genes into cultivated
      peanut, a linkage map based on microsatellite markers was constructed, using an
      F(2) population obtained from a cross between two diploid wild species with AA
      genome (A. duranensis and A. stenosperma). A total of 271 new microsatellite
      markers were developed in the present study from SSR-enriched genomic libraries,
      expressed sequence tags (ESTs), and by "data-mining" sequences available in
      GenBank. Of these, 66 were polymorphic for cultivated peanut. The 271 new markers
      plus another 162 published for peanut were screened against both progenitors and
      204 of these (47.1%) were polymorphic, with 170 codominant and 34 dominant
      markers. The 80 codominant markers segregating 1:2:1 (P<0.05) were initially used
      to establish the linkage groups. Distorted and dominant markers were subsequently
      included in the map. The resulting linkage map consists of 11 linkage groups
      covering 1,230.89 cM of total map distance, with an average distance of 7.24 cM
      between markers. This is the first microsatellite-based map published for
      Arachis, and the first map based on sequences that are all currently publicly
      available. Because most markers used were derived from ESTs and genomic libraries
      made using methylation-sensitive restriction enzymes, about one-third of the
      mapped markers are genic. Linkage group ordering is being validated in other
      mapping populations, with the aim of constructing a transferable reference map
      for Arachis.

PMID- 16088398
TI  - Molecular mapping of k2 Mdh1-n y20, an unstable chromosomal region in soybean
      [Glycine max (L.) Merr.].
AB  - In the soybean genome, a chromosomal region covering three tightly linked genes,
      k2, Mdh1-n, and y20, was found very unstable. It was suspected that the
      instability of the k2 Mdh1-n y20 chromosomal region was caused by a non
      autonomous transposable element residing adjacent to or in this region. In this
      study, we located and mapped this region with simple sequence repeat (SSR)
      markers on the soybean integrated map using five mapping populations. The k2 Mdh1
      n y20 chromosomal region was located on molecular linkage group H. The integrated
      map from five mapping populations consisted of 13 loci in the order Satt541,
      Satt469, Sat_122, Satt279, Satt253, Satt314, Mdh1-n,y20, k2, Satt302, Satt142,
      Satt181, and Satt434. The k2 Mdh1-n y20 chromosomal region was very close to
      Satt314, Satt253, and Satt279. The genetic distance between the Mdh1-n gene and
      Satt314 was less than 1 cM. The results of the mapping study were consistent with
      the results from previous studies that the Mdh1-n mutation in T261 (k2 Mdh1-n)
      and the Mdh1-n y20 mutation in T317 (Mdh1-n y20) were caused by deletions. In
      addition, another putative deletion was found in the genome of T261 which covered
      three SSR markers (Satt314, Satt253, and Satt279).

PMID- 16088399
TI  - Putrescine N-methyltransferase in Solanum tuberosum L., a calystegine-forming
      plant.
AB  - Putrescine N-methyltransferase (PMT, EC 2.1.1.53) catalyses the first specific
      step in the biosynthesis of tropane and nicotine alkaloids. Potato (Solanum
      tuberosum L.) contains neither nicotine nor the medicinal tropane alkaloids
      hyoscyamine or scopolamine, but calystegines. They are nortropane alkaloids with
      glycosidase inhibitory activity. Based on the assumption of calystegine formation
      by the tropane alkaloid pathway, PMT genes and enzymes were investigated in
      potato. Sprouting tubers contained both N-methylputrescine and PMT activity. Two
      cDNA clones coding for PMTs were obtained together with a cDNA clone for
      spermidine synthase (SPDS, EC 2.5.1.16). The pmt sequences resemble those from
      Nicotiana tabacum (85% identity) and those from tropane alkaloid plants, Atropa
      belladonna (80% identity) and Hyoscyamus niger (79% identity). They are less
      similar to SPDS of S. tuberosum (66% identity). Expression of pmt1 and spds cDNA
      in Escherichia coli yielded active enzymes, while pmt2 expression resulted in
      insoluble protein. Chimera proteins obtained by fusion of fragments of S.
      tuberosum pmt2 and H. niger pmt were active as PMT, if the initial part of pmt2
      was used, indicating that a mutation in the terminal part of the gene caused
      insolubility of the enzyme. PMT1 was purified after expression in E. coli and
      proved to be an active N-methyltransferase without SPDS activity. The enzyme was
      specific for putrescine (K (M) 250 microM) and inhibited by n-butylamine and
      cadaverine. While spds was transcribed in all plant organs, pmt transcripts were
      found in small tuber sprouts only. The results confirm that in potato genes and
      enzymes specific for the tropane alkaloid metabolism are expressed and active.

PMID- 16088400
TI  - The activity of ribosome modulation factor during growth of Escherichia coli
      under acidic conditions.
AB  - Expression of the gene encoding ribosome modulation factor (RMF), as measured
      using an rmf-lacZ gene fusion, increased with decreasing pH in exponential phase
      cultures of Escherichia coli. Expression was inversely proportional to the growth
      rate and independent of the acidifying agent used and it was concluded that
      expression of rmf was growth rate controlled in exponential phase under acid
      conditions. Increased rmf expression during exponential phase was not accompanied
      by the formation of ribosome dimers as occurs during stationary phase. Nor did it
      appear to have a significant effect on cell survival under acid stress since the
      vulnerability of an RMF-deficient mutant strain was similar to that of the parent
      strain. Ribosome degradation was increased in the mutant strain compared to the
      parent strain at pH 3.75. Also, the peptide elongation rate was reduced in the
      mutant strain but not the parent during growth under acid conditions. It is
      speculated that the function of RMF during stress-induced reduction in growth
      rate is two-fold: firstly to prevent reduced elongation efficiency by
      inactivating surplus ribosomes and thus limiting competition for available
      protein synthesis factors, and secondly to protect inactivated ribosomes from
      degradation.

PMID- 16088401
TI  - Expression of small intestinal and colonic phenotypes in complete intestinal
      metaplasia of the human stomach.
AB  - The incomplete intestinal metaplasia (IM) that is reported to be a risk factor
      for gastric carcinogenesis in man usually features sulfomucin production and thus
      is considered of colonic type. To cast light on the underlying mechanisms, we
      here examined the proportions of colonic and small intestinal phenotypes in IM by
      immunohistochemistry and real-time reverse transcription-polymerase chain
      reaction at the single isolated gland level. Carbonic anhydrase 1 (CA1) is a
      specific marker of colonic epithelial cells, whereas sucrase is specific to
      absorptive cells of the small intestine. Totals of 139 (23.5%) and 452 (76.5%) IM
      glands were judged to be CA1 positive and CA1 negative, respectively, in resected
      pyloric mucosa from cancer patients. The average score for MUC5AC in CA1-positive
      IMs was significantly lower than in CA1-negative counterpart tissue (P<0.0001),
      whereas the opposite was the case for sucrase (P<0.0001). High iron diamine
      Alcian blue staining revealed CA1 expression to coincide with type I complete IM.
      The expression of CA1 mRNA strongly correlated with that of sucrase-isomaltase,
      and inversely with that of MUC5AC in isolated IM glands. In conclusion, CA1 could
      be colocalized with small intestinal proteins such as sucrase, but only rarely
      with the gastric mucin, MUC5AC. Its expression warrants further study, with the
      focus on stimulation and/or suppression mechanisms by gastric and intestinal
      transcription factors.

PMID- 16088402
TI  - Classification of types of intraductal papillary-mucinous neoplasm of the
      pancreas: a consensus study.
AB  - Now that more than two decades have passed since the first reports of intraductal
      papillary-mucinous neoplasms (IPMNs), it has become clear that IPMN consists of a
      spectrum of neoplasms with both morphological and immunohistochemical variations.
      At a meeting of international experts on pancreatic precursor lesions held in
      2003, it was agreed that a consensus classification of IPMN subtypes should be
      established to enable a more detailed analysis of the clinicopathological
      significance of the variations. Based on our experience and on information from
      the literature, we selected representative histological examples of IPMNs and
      defined a consensus nomenclature and criteria for classifying variants as
      distinctive IPMN subtypes including gastric type, intestinal type,
      pancreatobiliary type, and oncocytic type. These definitions can be used for
      further analyses of the clinicopathological significance of the variations of
      IPMN.

PMID- 16088403
TI  - Well-differentiated papillary villoglandular adenocarcinoma of the uterine cervix
      with a focal high-grade component: is there a need for reassessment?
AB  - Well-differentiated villoglandular adenocarcinoma of the uterine cervix is
      characterized by an exophytic growth pattern with variably sized papillae that
      are lined by stratified columnar cells with no more than moderate cytologic
      atypia. Based on the favorable outcomes in most of the previously reported cases,
      it has been suggested that some patients with this subtype may be managed
      conservatively. The case described herein is an otherwise prototypical well
      differentiated villoglandular adenocarcinoma but which was associated with a 4.9
      mm focus of poorly differentiated carcinoma at its invasive edge. A review of the
      literature revealed a variety of findings that suggests a need to reassess the
      potential morphologic and biologic spectrum of this group of tumors. Five of the
      approximately 89 reported cases were associated with a higher-grade component of
      the same or a different histologic subtype. At least one patient with apparently
      stage 1A1 disease was found to have a positive lymph node. Another patient with
      stage 1B1 disease but no stromal invasion died of her disease following multiple
      recurrences. Finally, the frequency of lymphovascular invasion and/or lymph node
      involvement in recent series far exceeds what was found in the two original
      series. Our case suggests that well-differentiated villoglandular adenocarcinoma
      is not a diagnosis that should be unequivocally rendered on a small biopsy since
      other components may be present and the patients may be undertreated. We urge
      caution when conservative management (cone biopsy alone when margins are negative
      and there is no lymphovascular invasion) is offered to patients with this tumor
      since knowledge about its true biologic spectrum appears to still be in
      evolution.

PMID- 16088404
TI  - Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide,
      vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and
      mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19).
AB  - PURPOSE: The purpose of this study was to compare the efficacy and toxicity of
      bendamustine, vincristine + prednisone (BOP) with a standard regimen of
      cyclophosphamide, vincristine + prednisone (COP) in patients with previously
      untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell
      lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2),
      mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised
      to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) +
      bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a
      total of eight 21-day cycles. RESULTS: The rate of complete remission was 22%
      with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP
      and 46% with COP. The BOP-associated 5-year survival advantage almost reached
      significance in the subgroup of patients who responded to therapy (74% vs. 56%; P
      = 0.05), and did reach significance in responders who did not receive interferon
      maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both
      treatment groups, although alopecia and leucopenia were more severe with COP.
      CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide,
      as used in standard COP therapy, for the treatment of patients with indolent NHL
      and mantle cell lymphoma. Long-term survival data suggest a clinically
      significant benefit for patients treated with BOP.

PMID- 16088405
TI  - Impact of tumor control and presence of visible necrosis in head and neck cancer
      patients treated with radiotherapy or radiochemotherapy.
AB  - PURPOSE: Tumor volume after the lymph node involvement is one of the most
      important single prognostic factor in patients of head and neck cancers treated
      with radiotherapy. We have recently demonstrated that the hypoxic subvolume is
      more important than the total tumor volume. We therefore propose the hypothesis
      that the presence of visible necrosis might be an important factor for cure by
      radiotherapy in squamous cell cancers of the head and neck. METHODS: A total of
      51 patients with locally advanced inoperable (T3-4 or N2-3) squamous cell cancers
      of the head and neck (mean age 57 years, range 41-75 years) were prospectively
      investigated with regard to a possible impact of tumor volume. All patients
      received CT examination of the head and neck according to a standardized protocol
      (spiral CT, contrast enhancement after automatic injection), and the total tumor
      volume was calculated as the sum of volumes of all visible macroscopic tumor
      sites. Poorly perfused and necrotic areas (no contrast enhancement) within
      macroscopic tumor sites were also calculated. Patients were then treated with
      accelerated-hyperfractionated radiotherapy in about 6 weeks. Seventeen patients
      were treated with only radiation. Patients without contraindications to cisplatin
      chemotherapy received cisplatin chemotherapy or a combination of cisplatin and
      paclitaxel (N=34). The allocation of patients to certain treatment regimens was
      based on individual decisions in each case and not randomized. RESULTS: In
      patients treated with radiation alone, 12/17 (71%) got recurrence whereas in
      patients treated with radiation plus cisplatin, only 14/34 (41%) recurred
      (P=0.05). The 2-year overall survival was for radiation alone versus radiation
      plus cisplatin 0% vs. 62% (P<0.0008). Tumors with smaller amount of necrosis
      (necrosis volume<4 cm3) had a good prognosis irrespective of type of treatment
      (radiation alone or radiation plus cisplatin). However, patients with tumors with
      a larger amount of necrosis (necrosis volume> or =4 cm3) had a significantly
      better outcome if they were treated with radiation plus cisplatin as compared to
      patients treated with radiation alone. In a multi-variate analysis using a Cox
      regression model the type of treatment (radiotherapy plus versus without
      cisplatin) was the only independent prognostic factor for event-free survival
      (P<0.03) in the whole group. CONCLUSIONS: In this non-randomized retrospective
      investigation with limited sample size, radiation plus cisplatin was superior to
      radiation alone. This resulted mainly from a higher efficacy of the
      radiochemotherapy regimen in patients with large and especially necrotic tumors.
      The prognostic and predictive impact of visible necrosis should be further
      evaluated.

PMID- 16088406
TI  - Lead exposure levels and duration of exposure absence predict neurobehavioral
      performance.
AB  - OBJECTIVES: We investigated cognitive functions in currently lead exposed and
      formerly lead exposed men. The aim of the study was to verify the hypothesis that
      lead induced cognitive deficits are reversible. METHODS: Forty-seven lead exposed
      subjects with a mean blood level (PbB) of 30.8 microg/100 ml and 48 formerly
      exposed aged-matched subjects (PbB: 5.5 microg/100 ml) with the same socio
      economic background were investigated. Both groups were matched on verbal
      intelligence. Cognitive functions were assessed by using the Modified Wisconsin
      Card Sorting Test, Block Design Test, Visual Recognition Test, Simple Reaction
      Time, Choice Reaction and Digit Symbol Substitution. Lead exposure was assessed
      by using current and cumulative measures. The sample was divided according to
      their exposure duration versus exposure absence into four groups for subsequent
      ANOVA models analyses. RESULTS: Currently exposed men performed significantly
      worse in the Wisconsin Test and Block Design Test. No differences were found in
      the Visual Recognition Test, Simple Reaction Time, Choice Reaction and Digit
      Symbol Substitution. Splitting the sample according to their exposure duration
      versus exposure absence resulted in better cognitive performance of subjects with
      shorter exposure duration and longer exposure absence in the Block Design Test
      and the Wisconsin Test. CONCLUSIONS: Our results provide further evidence that
      cognitive deficits induced by occupationally lead are most likely reversible.

PMID- 16088407
TI  - Anemia is the strongest prognostic factor for outcomes of 5-fluorouracil-based
      first-line chemotherapy in patients with advanced gastric cancer.
AB  - OBJECTIVE: To examine the prevalence of anemia and its impact of hemoglobin (Hgb)
      levels in predicting outcomes of 5-fluorouracil (FU)-based first-line
      chemotherapy for patients with advanced gastric cancer (AGC). METHODS: We
      collected data retrospectively from 511 consecutive patients treated with FU
      based first-line chemotherapy as a routine clinical practice for AGC and followed
      up in two centers from 1995 to 2003. FU was given in combination with cisplatin
      (61%), taxanes (12%), anthracyclines (24%) and/or folinic acid (50%). RESULTS:
      Hgb values were <10 g/dl in 41%, and patients with baseline Hgb levels <10 g/dl
      had significantly lower response rates (9%) than patients with Hgb > or = 10 g/dl
      (53%; P < 0.001). In addition, Hgb < 10 g/dl served as a predictor for disease
      progression (RR, 1.77; 95% CI, 1.42-2.21) and death (RR, 1.85; 95% CI, 1.48-2.32)
      along with chemotherapy response and performance status. CONCLUSION: Low baseline
      Hgb level is a strong and independent prognostic factor for the outcomes of AGC
      patients receiving FU-based first-line chemotherapy. This results strongly
      suggest that Hgb level, along with performance status, may be considered as a
      stratification variable in subsequent studies of AGC.

PMID- 16088408
TI  - The effects of increasing doses of noradrenaline on systemic and renal
      circulations in acute bacteraemic dogs.
AB  - OBJECTIVE: To determine the dose-response effects of noradrenaline on the
      systemic and renal circulations during septic shock. DESIGN AND SETTING:
      Prospective controlled experiment in a university animal laboratory. SUBJECTS:
      Eight anaesthetized dogs. INTERVENTIONS: Transonic flow probes were surgically
      placed on the aorta via a left lateral thoracotomy and on the left renal artery.
      Blood pressure was measured from the femoral artery. Acute bacteraemia shock was
      induced by injecting Escherichia coli bacteria intravenously. Increasing doses of
      noradrenaline (0.1, 0.2, 0.3, 0.4, 0.5 microg kg(-1) min(-1)) were infused
      intravenously for 30 min at 30-min intervals. The model was first validated in
      four dogs. MEASUREMENTS AND RESULTS: Mean arterial pressure, central venous
      pressure, cardiac output, and renal blood flow were measured. Systemic vascular
      resistance was derived. Induction of bacteraemia decreased mean arterial
      pressure, central venous pressure and systemic vascular resistance. Cardiac
      output slightly increased. Noradrenaline produced linear dose-dependent increases
      in both mean arterial pressure and systemic vascular resistance. The response was
      attenuated during bacteraemia. Under non-bacteraemic conditions the maximum dose
      of noradrenaline reduced the renal blood flow from 12+/-1 to 10+/-1 ml kg(-1)
      min(-1). Bacteraemia further reduced renal blood flow to 7+/-1 ml kg(-1) min(-1),
      which was partly restored by the maximum dose of noradrenaline to 11+/-3 ml kg(
      1) min(-1). CONCLUSIONS: Noradrenaline can restore mean arterial pressure in
      bacteraemic shock and increases in mean arterial pressure are dose-dependent. The
      noradrenaline response is attenuated by bacteraemic shock. In bacteraemic shock
      noradrenaline also improves renal perfusion, as perfusion pressure increases.
      However, renal blood flow is not fully restored, suggesting that an element of
      impairment of renal blood flow exists due to the bacteraemia or noradrenaline.

PMID- 16088409
TI  - Noradrenaline and the kidney: foe, friend, or both?

PMID- 16088410
TI  - Allele frequencies for 15 STR loci in a population from the Republic of
      Macedonia.
AB  - Allele frequencies of 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358,
      TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, and FGA)
      were determined in a sample of 163 unrelated individuals from the Republic of
      Macedonia. AmpFISTR Identifiler Kit (Applied Biosystems) was used for PCR
      amplification. For all 15 loci, the combined matching chance is 6.6 x 10(18) and
      the power of exclusion is 99.999954%.

PMID- 16088411
TI  - Characterization of mtDNA SNP typing and mixture ratio assessment with
      simultaneous real-time PCR quantification of both allelic states.
AB  - We performed a study on the forensic utility of allele-discriminatory
      quantitative real-time PCR (rtPCR) using Minor Groove Binder TaqMan probes,
      targeting the highly variable mitochondrial single nucleotide polymorphism
      16519T/C. The apparent single-cycle PCR efficiency was virtually 100% for both
      16519 alleles. The allele designations made by rtPCR were concordant with the
      results obtained in a previous study by sequencing analysis. In heteroplasmic
      samples, minor allele proportions down to 9% were unambiguously detected and
      quantified. The variation in allele proportion estimates was essentially the same
      within and between different rtPCR runs, and the differences between total copy
      number estimates found for rerun samples were comparable to those found with non
      allele-discriminatory quantitative rtPCR assays.

PMID- 16088412
TI  - Inhibitory effects of verapamil isomers on the proliferation of choroidal
      endothelial cells.
AB  - PURPOSE: To evaluate the effects of verapamil isomers on in vitro proliferation
      of bovine choroidal endothelial cells (CECs). MATERIALS AND METHODS: CECs were
      isolated from bovine eyes and cultured in endothelial growth medium (EGM). For
      the proliferation assays, CECs were exposed to verapamil isomers (0.1-100 microM)
      in EGM with 2% fetal bovine serum or basic fibroblast growth factor (bFGF) (10
      ng/ml). After 72 h of incubation with the desired drug, the cellular
      proliferation was determined by an MTT assay and a BrdU assay. In addition, the
      drug toxicity on CECs stimulated with EGM was evaluated by cell counting with
      trypan blue. RESULTS: All verapamil isomers inhibited the bFGF- or medium
      stimulated growth significantly in a concentration range of 10-40 microM without
      toxicity. No significant differences were seen between the inhibitory effects of
      the various isomers. Cell toxicity was detected at a concentration of 100 microM
      verapamil isomers on EGM-stimulated CECs. CONCLUSION: The results demonstrate the
      efficacy of all verapamil isomers in inhibiting CEC proliferation involved in the
      process of choroidal neovascularization. D: -(+)-Verapamil may be recommended for
      further in vivo evaluation in an animal model of exudative AMD; it has fewer
      systemic and local side effects because calcium channels are not blocked.

PMID- 16088413
TI  - Intravenous nicotine self-administration in rats: effects of mecamylamine,
      hexamethonium and naloxone.
AB  - The rate and pattern of lever pressing were studied in 18 rats during 24-h
      sessions in which responding resulted in intravenous infusions of nicotine. There
      were four indications of the positive reinforcing effect of nicotine: (1) a
      greater number of lever presses when nicotine was response-contingent compared to
      when saline was available; (2) a greater number of responses on the lever
      resulting in an infusion of nicotine than on the control lever; (3) systematic
      decreases in the number of contingent nicotine infusions when nicotine was
      delivered noncontingently; and (4) systematic changes in the frequency of lever
      pressing as a function of dose. Under a fixed ratio 1 (FR 1) schedule, the number
      of infusions first increased and then decreased as the dose of nicotine was
      decreased (64, 32, 16, and 8 microg/kg infusion) and nicotine intake (mg/kg every
      24 h) was directly related to the infusion dose. As the FR size was increased
      from 1 to 6, the number of lever presses increased and the number of infusions
      (32 microg/kg) remained stable. At FR values greater than 6, both the number of
      lever presses and infusions decreased. Presession injections of mecamylamine
      (0.75, 1.5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose
      related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.)
      or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c.) did not alter the within- or between
      session patterns of nicotine self-administration. Under the conditions of the
      present experiment, nicotine served as an effective reinforcer and the behavior
      was shown to be sensitive to both FR size and infusion dose. In addition, the
      results suggest that nicotine self-administration involves central nicotinic
      receptors and that opioid receptor antagonism has no effect on nicotine's
      reinforcing effects in rats.

PMID- 16088414
TI  - Effects of asynchrony on symmetry perception.
AB  - The effect of temporal image segmentation on symmetry perception was investigated
      by means of stimuli composed of one part surrounding another. The two parts could
      be presented synchronously or with a temporal offset (20-100 ms), and each part
      could be either symmetrical or random. The task was to discriminate completely
      symmetrical (S) stimuli (in Experiment 1) or completely random (R) stimuli (in
      Experiment 2) from partially symmetrical (PS) stimuli in which one part was
      symmetrical and the other random. The R stimuli showed an asynchrony effect but
      the S stimuli did not. Furthermore, in both experiments, the PS stimuli showed an
      asynchrony effect when the symmetrical part was presented last but not when the
      symmetrical part was presented first (independent of whether it was the
      surrounded part or the surrounding part). Both results suggest that symmetry is
      strong enough to override this kind of temporal image segmentation.

PMID- 16088415
TI  - Combining pulse oximetry and clinical examination in screening for congenital
      heart disease.
AB  - The objective of this study was to evaluate combined pulse oximetry and clinical
      examination as a screening method for congenital heart disease (CHD) in
      asymptomatic newborns. Asymptomatic newborns were screened for CHD using pulse
      oximetry and clinical examination before their discharge from the nursery. Oxygen
      saturation > or =94% was considered normal. Echocardiography was done for
      newborns with abnormal readings and for those with significant murmurs. Data
      concerning undetected cases were collected from the pediatric referral hospital.
      A total of 5211 cases were screened. Echocardiographic evaluations were done
      based on low pulse oximetry in five cases and on murmur detection in ten others.
      The sensitivity of the combined method of screening was 77%, whereas it was 31%
      for oximetry alone and 46% for clinical examination alone. Specificity was
      approximately 100% for all methods. The positive predictive value of the combined
      tool was 66.7%. We conclude that combining pulse oximetry and clinical
      examination can enhance the clinician's ability to detect life-threatening CHD in
      a timely manner. This screening method should become a part of the discharge plan
      for every newborn.

PMID- 16088416
TI  - Liver herniation into the pericardium: an unusual cause of massive pericardial
      effusion with intrapericardial mass in a neonate.
AB  - In neonates presenting with massive pericardial effusion and pericardial mass,
      liver herniation into the pericardium is a rare diagnosis. Echocardiogram and CT
      scan are useful investigations in the diagnosis of pericardial masses.
      Continuation of the mass with the liver with the same texture as the liver helps
      to make the diagnosis of intrapericardial herniation of liver. Correct diagnosis
      of this condition is important because the surgical approach needed for
      management of this condition is different from that used for other pericardial
      masses.

PMID- 16088417
TI  - Dysphagia lusoria caused by aberrant right subclavian artery, Kommerell's
      diverticulum, legamentum ring, right descending aorta, and absent left pulmonary
      artery: a report of a unique vascular congenital disease undetected until
      adulthood and a review of the literature.
AB  - An active otherwise healthy and middle-aged woman presented with left
      supraclavicular pulsation, right upper extremity claudication, and mild
      dysphagia. Evaluation revealed an aberrant right subclavian artery, Kommerell's
      diverticulum with aneurysmal degeneration, legamentum arteriosum completing
      vascular ring, and absent left pulmonary artery with multiple collateral supply
      to the left lung. She underwent successful surgical repair via right thoracotomy,
      including division of the vascular ring, resection of the diverticulum and
      aneurysm, and finally reimplantation of the right subclavian artery to the aortic
      arch. Her symptoms resolved completely, and she was able to resume normal
      activities.

PMID- 16088418
TI  - Bilateral coronary artery dilatation and supravalvular pulmonary stenosis in a
      child with noonan syndrome.
AB  - Noonan syndrome is the second most frequent congenital malformation syndrome,
      after Down syndrome, associated with cardiovascular abnormalities. The most
      prevalent cardiovascular abnormalities in Noonan syndrome are pulmonary stenosis
      and hypertrophic cardiomyopathy. We report the case of a 12-year-old girl with
      Noonan syndrome who had multiple cardiovascular abnormalities, including
      extensive bilateral coronary artery dilatation, valvular and supravalvular
      pulmonary stenosis, atrial septal defect, and mitral valve prolapse. Both
      coronary artery dilatation and supravalvular pulmonary stenosis, although rarely
      reported, are abnormalities of the cardiovascular system that may occur in Noonan
      syndrome.

PMID- 16088419
TI  - Cardiac thrombus in Omenn syndrome.
AB  - Omenn syndrome is characterized by a generalized erythematous skin rash, lymph
      node enlargement, hepatosplenomegaly, Increased serum IgE levels, eosinophilia,
      and evidence of severe combined immune deficiency. Patients develop fungal,
      bacterial, and viral infections. We present the case of a 3-month-old girl with
      Omenn syndrome who developed right ventricular thrombosis. Echocardiographic
      study revealed a round structure that filled the apex and corpus of the the right
      ventricle. We investigated this patient for hypercoagulation and made a diagnosis
      of ventricular thrombosis, which is an uncommon finding in Omenn syndrome.

PMID- 16088420
TI  - A new approach to accurate diagnosis of acute appendicitis.
AB  - This study aimed (1) to develop a simple scoring system incorporating ultrasound
      (US) examination and clinical or laboratory predictors for increasing diagnostic
      accuracy in acute appendicitis (AA), and (2) to evaluate the performance of the
      scoring system as compared to that of previous models. Fifteen variables
      including US assessment for patients admitted with suspected AA were considered
      in multivariate analysis using the finding of AA at operation as the end point
      (internal study). The new score, together with 11 previous ones, was applied to a
      prospective independent population of subjects with suspected AA, and the
      respective performances were compared (external validation study). Among 303
      patients (170 males, mean age 28.3 +/- 13.3 years) of the internal study, 161
      went on to surgery, and 130 had AA at operation. Four independent correlates of
      AA were identified and used for the derivation of the following integer-based
      scoring system: number of points = 6 for US demonstrating AA + 4 for tenderness
      in the right lower quadrant + 3 for rebound tenderness + 2 for leukocyte count
      >12,000/microl. In the external study (201 subjects, 105 males, mean age 28.7 +/-
      11.9 years, 109 operated, 87 with AA), when the cut-off of >/or = 8 points for AA
      was used, sensitivity, specificity, accuracy, and area under the curve of the
      proposed score were 95.4%, 97.4%, 96.5%, and 93%, respectively, exceeding
      noticeably the previous models. The proposed scoring system introduces a
      quantitative combination of the clinical evaluation with US imaging and a marker
      of inflammatory response, which may enhance the diagnostic accuracy for subjects
      with suspected AA especially in geographical areas where CT scanning is not
      readily available on a 24-hour basis.

PMID- 16088421
TI  - Hydatid disease of the abdomen and other locations.
AB  - We present patients treated for hydatid disease in our hospital (in northeastern
      Greece) over the last 20 years. In the period from 1984 to 2003, a total of 135
      patients (54 male, 81 female) were treated for echinococcal disease (age 15-85
      years). In 111 (82.2%) patients only the liver was affected; 9 (6.7%) patients
      had concomitant hepatic and extrahepatic hydatid disease; and 15 (11.1%) patients
      had only extrahepatic disease. Clinical symptoms in patients with hepatic
      locations of the disease included abdominal pain localized in the epigastrium or
      right upper quadrant of the abdomen, tenderness, hepatomegaly with palpable
      abdominal mass, jaundice, fever, and anaphylactic reaction. All the patients were
      treated surgically. Surgical techniques included partial cystectomy and drainage,
      cystectomy and capitonage, cystectomy and omentoplasty, only drainage, left
      lateral hepatectomy, total pericystectomy, and laparoscopic pericystectomy.
      Rupture into the bile duct was managed by T-tube drainage or biliodigestive
      anastomosis. Symptoms and surgical treatment for extrahepatic cysts varied
      according to the location of the cyst. The median cyst diameter of all patients
      was 11 cm. The postoperative complication rate was 17.0%. Two patients died
      (1.5%). The median hospital stay was 18 days. The recurrence rate was 6.7%. The
      study suggests that treatment of this benign disease should be the less radical
      surgical technique combined with pre- and postoperative anthelmintic
      administration. The surgical treatment should be combined with careful use of
      scolicidal fluids and aspiration of the cyst to avoid contamination and minimize
      the risk of recurrence.

PMID- 16088422
TI  - Hepatectomy as treatment of choice for hepatocellular carcinoma in elderly
      cirrhotic patients.
AB  - In recent decades liver resection has become a safe procedure; however, the
      outcome of hepatectomies in aged cirrhotic patients is often uncertain. To
      elucidate early and long-term outcomes of hepatectomy for HCC in the elderly, we
      studied 241 cirrhotic patients who underwent liver resection for HCC between 1985
      and 2003. According to their age at the time of surgery, patients were divided
      into two groups: aged > 70 years (64 patients) and aged < or = 70 years (177
      patients). Operative mortality was 3.1% in the elderly and 9.6% in the younger
      group (p = 0.113). Postoperative morbidity and liver failure rates were higher in
      the younger group (42.4% versus 23.4%, p = 0.0073; 12.9% versus l.6%, p =
      0.0065). Five-year survival rates are 48.6% in the elderly group and 32.3% in the
      younger group (p = 0.081). Considering only radical resections in Child-Pugh A
      patients, survival remains similar in the two groups (p = 0.072). Disease-free
      survival is not different in the two groups. A survival analysis performed
      according to the tumor diameter shows a better survival for elderly Child-Pugh A
      patients with HCC larger than 5 cm radically resected (50.8% versus 16.1% 5-year
      survival, p = 0.034). In univariate analysis, tumor size is not a prognostic
      factor in the elderly, whereas younger patients with large tumors have a worse
      outcome. Age by itself is not a contraindication for surgery, and selected
      cirrhotic patients with HCC who are 70 years of age or older could benefit from
      resection, even in the presence of large tumors. Long-term results of liver
      resections for HCC in the elderly may be even better than in younger patients.

PMID- 16088423
TI  - Do Germans keep patients too long in hospital? A prospective randomized trial.
AB  - Cost-effectiveness reduces hospital stay for all patients with thyroid surgery
      but lacks information on medical comparability and patients' fulfilled
      expectations. The aim of this study was to assess if a hospital stay of 2 days
      after thyroid surgery had a negative influence on the medical quality or on
      health-related quality of life. In a controlled prospective randomized trial with
      238 patients, a postoperative hospital stay of 2 days was compared to one longer
      than 2 days. The postoperative medical investigation included serum calcium
      levels, laryngeal nerve function, and suction drainage volume. Health-related
      quality of life was assessed on the day of admission before the operation and
      again 14 days after discharge. Fourteen days after discharge patients were also
      asked about their subjective health. Despite the study design, it was necessary,
      for ethical reasons, to let the patients decide when to leave the hospital. In
      the 2-day study group, 56.6% of the patients preferred hospitalization for more
      than 2 days (most choosing 3 days). Medical reasons were hyperthyroidism (p <
      0.02) and postoperative hypocalcemia (p < 0.03). In the control group 28% left
      the hospital after 2 days. Only 35% of the patients left the hospital at the
      second postoperative day, but 60% of these patient supported this shorter
      hospitalization. Health-related quality of life and self-rated health was
      significantly higher in patients leaving the hospital on the second postoperative
      day. A 2-day hospital stay after thyroid surgery is possible and does not show
      medical or health-related quality of life disadvantages in patients with an
      uncomplicated postoperative course who consider themselves healthy.

PMID- 16088424
TI  - Glucose intolerance modifies the inflammatory response after intestinal ischemia
      reperfusion.
AB  - Streptozotocin administration in newborn rats (nSTZ-rats) leads to adults with
      mild insulin deficiency and normoglycemia, and is accepted as a model of type 2
      diabetes. We examined possible differences in the production of inflammatory
      mediators between healthy and nSTZ-rats after ischemia-reperfusion (I-R). Two
      month-old control and nSTZ-rats were randomly separated into control and
      intestinal I-R groups. After reperfusion, samples were obtained from the portal
      vein (PV) infrahepatic cava vein (ICV), suprahepatic cava vein (SCV), jejunal
      wall, and pancreas. Nitric oxide (NO), lipid hydroperoxides (LPO), tumor necrosis
      factor alpha (TNF-alpha), 60 kDa receptor (sTNF-R1), 80 kDa (sTNF-R2), and
      intercellular adhesion molecule-1 (ICAM-1), were determined. After I-R, nSTZ-rats
      showed increased plasma concentrations of LPO, NO, ICAM-1 (0.5141 +/- 0.083 vs
      0.024 +/- 0.003, ICV; 0.574 +/- 0.075 vs 0.023 +/- 0.003, SCV; 0.528 +/- 0.067 vs
      0.027 +/- 0.003 PV; ng/ml), TNF-alpha (42.4 +/- 5.7 ICV, 248.4 +/- 28.2 SCV, and
      33.6 +/- 4.0 PV. In n STZ-rats, vs 4.36 +/- 0.57, 4.74 +/- 0.77, and 3.16 +/-
      0.32, respectively, in control rats; pg/ml), and sTNF-R1. Both TNF-alpha and NO
      plasma levels were higher in SCV than in ICV and PV after I-R. In addition, after
      I-R, jejunal wall of nSTZ-rats showed an increase of TNF-alpha IL-1, and IL-10
      levels. A pre-existing state of glucose intolerance intensifies the inflammatory
      response after intestinal I-R.

PMID- 16088427
TI  - Twenty-one commandments for the new surgeon in a small town.

PMID- 16088428
TI  - Displacement of adsorbed insulin by Tween 80 monitored using total internal
      reflection fluorescence and ellipsometry.
AB  - PURPOSE: This study was conducted to investigate the mechanism of action in the
      displacement of adsorbed insulin from a hydrophobic surface by Tween 80 and of
      the competitive adsorption of the two species. METHODS: Total internal reflection
      fluorescence (TIRF) and ellipsometry were used as in situ methods to examine the
      processes taking place at hydrophobic model surfaces in the presence of insulin
      and Tween 80. RESULTS: TIRF studies showed that the displacement of insulin by
      Tween 80 could be fitted to a sigmoidal function, indicating a nucleation
      dependent process. Furthermore, a linear dependence between the apparent rate
      constant and the logarithm of the Tween 80 concentration was found. Competitive
      adsorption from solution mixtures of insulin and Tween 80 indicated that insulin
      was adsorbed first, but subsequently displaced by the surfactant. This
      displacement proved also to be dependent on the concentration of Tween 80 in the
      mixture. CONCLUSIONS: The results indicate that Tween 80 at concentrations above
      critical micelle concentration can be used to protect insulin against surface
      adsorption. The presence of a lag phase in the displacement at low surfactant
      concentration indicates that the mechanism of action for Tween 80 to reduce
      adsorption of insulin may be by competing for sites at the surface.

PMID- 16088429
TI  - Immunoliposomes directed toward VCAM-1 interact specifically with activated
      endothelial cells--a potential tool for specific drug delivery.
AB  - PURPOSE: Immunoliposomes can be potentially used as carriers for drug delivery to
      specific cells. The aim of this paper was to exploit the overexpression of
      vascular cell adhesion molecule-1 (VCAM-1) on activated human endothelial cells
      (HEC) for targeting of anti-VCAM-1 coupled liposomes with the intent for further
      use as drug carriers. METHODS: TNF-alpha-activated HEC were exposed to liposomes,
      either plain or coupled with antibodies to VCAM-1 (L-VCAM-1) or to irrelevant IgG
      (L-IgG); nonactivated HEC subjected to the same conditions were used as control.
      For binding studies, the cells were incubated with fluorescently labeled
      liposomes at 4 degrees C, and after 2 h, fluorescence intensity was assessed by
      flow cytometry; specificity of binding was determined by performing the
      experiments in the presence of excess anti-VCAM-1. Cellular internalization of
      liposomes was studied employing radioactively or fluorescently labelled
      liposomes; to detect the mechanisms of uptake, experiments were performed in the
      presence of agents that interfere in the endocytotic pathway. Transmigration of
      liposomes was monitored in a two-chamber culture model. The effect of L-VCAM-1
      binding to HEC on intracellular calcium ([Ca(2+)](i)) and distribution of actin
      was determined by fluorimetry and fluorescence microscopy. RESULTS: (1) L-VCAM-1
      binds selectively and specifically to TNF-alpha activated HEC. (2) Approximately
      50% of L-VCAM-1 is taken up by receptor-mediated endocytosis via clathrin-coated
      vesicles. (3) Binding of L-VCAM-1 to HEC surface induces a rise in [Ca(2+)](i)
      and reorganization of actin filaments. (4) A small percentage of liposomes
      migrates across HEC. CONCLUSION: The data indicate that VCAM-1 may be an
      appropriate target for specific drug delivery to activated HEC using
      immunoliposomes.

PMID- 16088432
TI  - Pulmonary rehabilitation and COPD.
AB  - Pulmonary rehabilitation has been well established and increasingly recommended
      in disease management plans for patients with chronic obstructive pulmonary
      disease. Key elements include a multidisciplinary approach to care, focus on the
      individual patient, and attention to emotional and social as well as physical
      aspects of health. Appropriate candidates are symptomatic patients with chronic
      lung disease who are aware of their disability and motivated to participate
      actively in their own health care. Pulmonary rehabilitation has also been useful
      for patients with other types of chronic lung diseases. Program components
      include a careful patient evaluation, education, instruction in respiratory and
      chest physiotherapy techniques, exercise training, and psychosocial support.
      Benefits demonstrated in a growing body of evidence include improvement in
      symptoms, exercise tolerance, and quality of life and reduction in utilization of
      health care resources. Pulmonary rehabilitation has also been included as an
      adjunct to surgical programs such as lung transplantation and lung volume
      reduction surgery.

PMID- 16088433
TI  - Pathogenesis of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized and defined by
      limitation of expiratory airflow. This can result from several types of
      anatomical lesions, including loss of lung elastic recoil and fibrosis and
      narrowing of small airways. Inflammation, edema, and secretions also contribute
      variably to airflow limitation. Smoking can cause COPD through several
      mechanisms. First, smoke is a powerful inducer of an inflammatory response.
      Inflammatory mediators, including oxidants and proteases, are believed to play a
      major role in causing lung damage. Smoke can also alter lung repair responses in
      several ways. Inhibition of repair may lead to tissue destruction that
      characterizes emphysema, whereas abnormal repair can lead to the peribronchiolar
      fibrosis that causes airflow limitation in small airways. Genetic factors likely
      play a major role and probably account for much of the heterogeneity
      susceptibility to smoke and other factors. Many factors may play a role, but to
      date, only alpha-1 protease inhibitor deficiency has been unambiguously
      identified. Exposures other than cigarette smoke can contribute to the
      development of COPD. Inflammation of the lower respiratory tract that results
      from asthma or other chronic disorders may also contribute to the development of
      fixed airway obstruction. COPD is not only a disease of the lungs but is also a
      systemic inflammatory disorder. Muscular weakness, increased risk for
      atherosclerotic vascular disease, depression, osteoporosis, and abnormalities in
      fluids and electrolyte balance may all be consequences of COPD. Advances in
      understanding the pathogenesis of COPD have the potential for identifying new
      therapeutic targets that could alter the natural history of this devastating
      disorder.

PMID- 16088434
TI  - A review of alpha-1 antitrypsin deficiency.
AB  - Alpha-1 antitrypsin (AAT) is a protein that prevents enzymes such as elastin from
      degrading normal host tissue. Individuals who are deficient in AAT (those with
      levels < 11 micromol/L) are at risk for developing such clinical manifestations
      as emphysema, cirrhosis, panniculitis, and anticytoplasmic neutrophilic antibody
      (C-ANCA)-positive vasculitis (Wegener's granulomatosis). Estimates suggest that
      75 to 85% of those with severe deficiency of AAT will develop emphysema. Smoking
      appears to be the most important risk factor for the development of emphysema
      among AAT deficient persons. Severe deficiency of AAT also seems to be associated
      with a shorter lifespan. Among smokers, mild to moderate reductions in AAT levels
      may be associated with a more rapid decline in lung function. Diagnosis of AAT
      deficiency is made by measuring serum levels of AAT and, if reduced, an effort
      should then be made to identify the genetic abnormality responsible for the
      reduction. A recent evidence-based review has offered testing recommendations for
      AAT deficiency and includes the recommendation that all patients with COPD be
      tested for AAT deficiency. Augmentation with an intravenous form of purified
      pooled human plasma has been shown to increase the serum levels of AAT among
      deficient patients and its use appears to impact the rate of forced expiratory
      volume in 1 second (FEV (1)) decline and overall survival; to date, no
      confirmatory, large, prospective, randomized trials are available.

PMID- 16088435
TI  - Surgical therapy for chronic obstructive pulmonary disease.
AB  - Many patients with severe chronic obstructive pulmonary disease (COPD) experience
      incapacitating breathlessness and exercise limitation. Multiple surgical
      techniques have been utilized to achieve resection of giant, localized bullae
      with documented short-term benefit in pulmonary function and dyspnea in highly
      selected patients. The poorest long-term outcome has been noted in those with
      greater degrees of emphysema in the remaining lung, greater underlying chronic
      bronchitis, and a bulla occupying less than one third of the hemithorax,
      particularly if compressed normal lung is not evident. Lung volume reduction
      surgery (LVRS) in the absence of giant bullae has become more widely accepted in
      selected patients. Bilateral LVRS procedures appear to result in greater short
      term improvement than unilateral LVRS, whereas physiological benefits appear
      similar with video-assisted thoracoscopy (VATS) or median sternotomy (MS)
      techniques. Improvement in dyspnea and health status after LVRS has been
      documented and appears to be better preserved over longer-term follow-up than
      physiological improvement. Clear direction has been provided in identifying
      optimal candidates for bilateral LVRS; patients with a postbronchodilator forced
      expiratory volume in 1 second (FEV (1)) < or = 20% predicted and a diffusing
      capacity for carbon monoxide (DL (CO)) < or = 20% predicted or homogeneous
      emphysema exhibit a much higher mortality with LVRS than with medical management.
      Patients with upper-lobe predominant emphysema and a low postrehabilitation
      exercise tolerance exhibited a decreased risk of mortality after LVRS. Patients
      with non-upper lobe predominant emphysema on high-resolution computed tomography
      (HRCT) and a high postrehabilitation exercise capacity exhibit an increased risk
      of death after LVRS. Patients with upper lobe predominant emphysema and a high
      postrehabilitation exercise capacity or patients with non-upper lobe predominant
      emphysema and a low postrehabilitation exercise capacity do not have a survival
      advantage or disadvantage, whereas those with upper lobe predominant emphysema
      treated surgically are more likely to improve their exercise capacity after
      surgery. Lung transplantation is an option for a more limited number of patients.
      Consistent short-term spirometric improvement after both single- and double-lung
      transplant has been documented. Long-term results of lung transplantation are
      limited by significant complications that impair survival; an approximately 80% 1
      year, 50% 5-year, and 35% 10-year survival has been reported. Bronchiolitis
      obliterans is the most important long-term complication of lung transplantation
      resulting in decreased pulmonary function. In general, a COPD patient can be
      considered an appropriate candidate for transplantation when the FEV (1) is below
      25% predicted and/or the paCO (2) is > or = 55 mm Hg.

PMID- 16088436
TI  - Pathogenesis and treatment of acute exacerbations of chronic obstructive
      pulmonary disease.
AB  - Once thought to be a mere nuisance, exacerbations are now recognized as a major
      contributor to the morbidity and mortality associated with chronic obstructive
      pulmonary disease. This recognition has led to research using new investigative
      tools that has substantially enhanced our understanding of the pathogenesis of
      exacerbations. Several overlapping etiologies can precipitate the symptom complex
      of an exacerbation. Treatment of exacerbations requires the use of several
      therapeutic modalities with the goal of restoring the patient to baseline.
      Results of recent clinical trials and observational studies have allowed a
      refinement of the approach to treatment of exacerbations. These include a
      rational, stratified approach to the use of antibiotics and several trials
      substantiating the use of systemic corticosteroids. Relapse or failure rates of
      20 to 33% have been described in the treatment of acute exacerbation, with these
      treatment failures contributing substantially to the costs associated with
      exacerbations. Improved treatment based on enhanced understanding and good
      clinical evidence should lead to better outcomes in this common clinical entity.

PMID- 16088437
TI  - Epidemiology and global impact of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a preventable and treatable
      disease that causes a heavy health and increasing economic burden both in the
      United States and around the world. Most of the risk factors for COPD are well
      known and include smoking, occupational exposures, air pollution, airway
      hyperresponsiveness, asthma, and certain genetic variations, although many
      questions, such as why a minority of smokers develop significant airway
      obstruction, remain. Major medical organizations have agreed on a common
      definition of COPD, although newer measures, such as functional status or
      exercise capability, have emerged as important in determining the prognosis of
      COPD patients. In most of the world, COPD prevalence and mortality are still
      increasing and will likely continue to rise in response to increases in smoking,
      particularly by women and adolescents. Resources aimed at smoking cessation and
      prevention, COPD education and early detection, and better treatment will be of
      the most benefit in our continuing efforts against this important cause of
      morbidity and mortality.

PMID- 16088438
TI  - New concepts in the radiological assessment of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a complex genetic disorder in
      which environmental factors, such as tobacco smoke, interact with genetic
      susceptibility to cause disease. Airway obstruction in COPD is due to an
      exaggerated inflammatory response that ultimately destroys the lung parenchyma
      (emphysema) and increases airway resistance by remodeling the airway wall. Until
      recently, assessment of these disease processes required the examination of
      resected tissue. However, computed tomography (CT) now allows researchers to
      measure the structure of the lung parenchyma and airway wall without having to
      remove the tissue. This review describes some of the new CT techniques for
      quantitative assessment of lung structure. These techniques are extremely
      important to study the pathogenesis of COPD as well as differentiate patients
      with predominantly emphysema disease from those with airway wall remodeling, and
      to assess the effects of therapeutic interventions.

PMID- 16088439
TI  - Role of bronchodilators in chronic obstructive pulmonary disease.
AB  - The prevalence of chronic obstructive pulmonary disease (COPD) continues to be on
      the rise. Bronchodilators are first line agents for the symptomatic management of
      this disease and have proven to be effective in both stable disease status and
      exacerbations. The stepwise escalation of therapy for COPD according to severity
      has been outlined in international guidelines. Different classes of
      bronchodilators exist. The most experience is available for short-acting beta
      agonists and anticholinergics. These agents are mainly recommended for the
      treatment of mild COPD and for symptomatic patients on an as needed basis. Long
      acting beta-agonists and anticholinergics have been developed more recently. They
      are more convenient to use for patients with advanced disease who require
      maintenance therapy with bronchodilators, and have been shown in this group of
      patients to provide superior efficacy compared with short-acting agents.
      Tiotropium, a long-acting anticholinergic, appears to be particularly powerful
      and may eventually replace ipratropium as the primary agent for COPD treatment.
      In contrast, the usage of theophylline, which used to be part of the mainstay of
      treatment for COPD, has declined, mainly secondary to a narrow therapeutic margin
      and side effects, but it is inexpensive and still has its role. New agents like
      phosphodiesterase-4-inhibitors are interesting substances that may become
      important adjuncts in COPD management, but there is limited experience so far.
      None of the bronchodilators have been shown to change outcome in COPD, but this
      issue is under active investigation.

PMID- 16088440
TI  - The role of corticosteroids in chronic obstructive pulmonary disease.
AB  - Oral corticosteroids are powerful relatively nonspecific antiinflammatory agents
      with a range of well-characterized side effects. There is good evidence to show
      that they accelerate the rate of resolution of exacerbations of COPD and relapse
      is less likely if patients receive these drugs. Maintenance therapy with oral
      preparations is associated with worse mortality and skeletal muscle myopathy is a
      particular problem. Corticosteroids have little effect on biopsy proven
      inflammation or its surrogates in COPD and did not change the rate of decline of
      FEV (1) over a range of spirometric disease severity in a number of trials each
      lasting 3 years. However, meta-analysis of the data suggests that a small effect
      (up to 10 ml /year) might be present. There is more consistent evidence for an
      effect on postbronchodilator FEV (1) with both fluticasone propionate and
      budesonide. In patients with a postbronchodilator FEV (1) < 50% predicted where
      self-reported exacerbations become more common, inhaled corticosteroids can
      reduce the number of attacks. This effect is the major factor accounting for the
      reduction in deterioration in health status seen in patients who receive inhaled
      corticosteroids. Inhaled corticosteroids are much safer than oral therapy,
      although they do have a predictably higher incidence of candidiasis and
      hoarseness of the voice. Skin bruising is seen in patients with better lung
      function who use these drugs. Triamcinolone use is associated with reduction in
      bone density but this was not seen with budesonide. Combining an inhaled
      corticosteroid and a long-acting beta-agonist in the same inhaler increases the
      efficacy of the latte drug in COPD patients, with a significantly larger
      improvement in FEV (1), a larger reduction in reported breathlessness, and a
      reduction in exacerbation numbers in those with severe disease where beta
      agonists appear to be less effective. Inhaled corticosteroids are not suitable
      for monotherapy in COPD but can be helpfully combined with an inhaled
      bronchodilator in patients with symptomatic disease.

PMID- 16088441
TI  - Assessment of pulmonary function in COPD.
AB  - Pulmonary function testing is used in the diagnosis of chronic obstructive
      pulmonary disease (COPD) and the staging of COPD severity. The current diagnostic
      criterion for airflow obstruction is a ratio of forced expiratory volume in 1
      second (FEV (1)) to forced vital capacity (FVC) < 70%. However this absolute
      definition can lead to false-negative determinations in younger patients and
      false-positive determinations in the elderly. Nevertheless, screening spirometry
      is advocated and becomes feasible in the physician office setting with the
      availability of compact, relatively affordable apparatus that meets the
      appropriate technical specifications. Spirometry should be complemented by
      measurement of lung volumes using body plethysmography in those with evidence of
      airflow obstruction. Small airways disease can be detected by various techniques
      that measure airway and total respiratory system resistance. There is renewed
      interest in the forced oscillation technique and impulse oscillometry because of
      their noninvasiveness and potential ability to distinguish small from larger
      airway disease. Finally, pulmonary function testing has an important role in
      preoperative risk assessment; for example, in patients being considered for lung
      volume reduction surgery or resection of a lung nodule.

PMID- 16088442
TI  - Emerging concepts in outcome assessment for COPD clinical trials.
AB  - The selection of appropriate, clinically meaningful outcome measures for chronic
      obstructive pulmonary disease (COPD) clinical trials is a complex issue.
      Functional exercise measures are more likely to adequately reflect the effect of
      novel and emerging interventions than traditional physiological measures such as
      forced expiratory volume in 1 second (FEV (1)). Nonetheless, among several
      exercise measures commonly used, the choice is not a simple issue and should be
      based upon rational as well as pragmatic issues. This is because important
      measurement properties (validity and responsiveness) can differ among exercise
      measures, among different interventions, and across degrees of disability.
      Furthermore, "free-living" daily activity measures may be more meaningful
      measures than these "in-lab" exercise measures for future clinical trials of
      COPD, although their reproducibility, validity, and responsiveness have not yet
      been adequately studied. Application of these and other emerging concepts in
      outcome assessment for COPD clinical trials will be examined.

PMID- 16088444
TI  - Role and development of TH1/TH2 immune responses in the lungs.
AB  - The development of T helper 1 (Th1) and Th2 responses is dependent on the cells
      and early signals of the innate immune system. Following inhalation of pulmonary
      pathogens, lung antigen-presenting cells (APCs) ingest the microbe, begin to
      process antigen, and migrate to peripheral lymphoid tissues (i.e., LALNs). It is
      in the lymph node that the APC-T cell interaction takes place; therefore, the
      microenvironment of the lymph node significantly influences the developing T cell
      response (Th1 vs Th2). Several factors can determine the nature of the T cell
      response, including cytokines, chemokines, microbial virulence factors, and
      dendritic cell phenotype. A shift in the Th1/Th2 balance in the lungs can result
      in chronic infection, allergic disease, and immunopathology. This review
      discusses the mechanisms of developing Th1/Th2 pulmonary responses, the
      counterregulation of Th1/Th2 immunity, and the consequences of immune deviation
      in the lungs.

PMID- 16088445
TI  - Initiation of lung immunity: the afferent limb and the role of dendritic cells.
AB  - The lung is the largest epithelial surface in the body and constitutes a major
      portal of entry for microorganisms. Dendritic cells (DCs) are bone marrow-derived
      cells that populate the respiratory tract from the nasal mucosa to the lung
      pleura. DCs are dexterous cells playing a role in both the innate and the
      adaptive immune responses. DCs can respond to dangers in the lung by immediately
      generating protective cytokines that stimulate natural killer (NK) cells to
      produce cytokines and kill targets. Direct (by pathogen recognition receptors)
      and indirect (by inflammatory cytokines) recognition of the infectious agent can
      also trigger signaling pathways in the DCs that activate an integrated
      developmental program called maturation, which transforms DCs into efficient
      antigen-presenting cells (APCs) for naive T cell stimulation. Furthermore, DCs
      play a role in generating effector B cells in the lymph nodes draining the lung.
      This review focuses on how DCs sense the health of the lung and translate
      messages regarding the lung microenvironment to cells of the innate and adaptive
      immune response to initiate effector functions to clear an invading microorganism
      [T helper 1 (Th1) or Th2 response] or generate tolerance [T regulatory (Tr),
      anergy, or deletion] to inhaled antigen when no danger is sensed.

PMID- 16088446
TI  - Macrophages in innate and acquired immunity.
AB  - Alveolar macrophages play a central role in pulmonary host defense. When foreign
      particles or pathogens enter the respiratory tract, constitutively present innate
      host defenses attempt to clear the challenge. Alveolar macrophage phagocytosis of
      foreign material is a critical component of this response, as is secretion of
      inflammatory mediators designed to combat invading pathogens. If the pathogenic
      burden is too large and overwhelms innate immunity, then acquired immune
      responses are initiated resulting in the generation of antigen-specific cellular
      and humoral immunity. In response to evolutionary pressures to minimize
      unnecessary inflammation in the lower respiratory tract, alveolar macrophages are
      generally poor accessory cells in the initiation of specific immunity. However,
      in many circumstances, especially those associated with cellular activation,
      alveolar macrophages can play an important role in the generation and expansion
      of pulmonary immune responses. This review discusses the role of alveolar
      macrophages in innate and acquired pulmonary host defense.

PMID- 16088447
TI  - Neutrophils in innate immunity.
AB  - Neutrophils are an important component of innate immunity in the lungs. During
      bacterial pneumonia, neutrophils are recruited from the capillaries of the
      pulmonary circulation in the gas-exchanging regions of the lungs. This process
      requires the coordinated activation of many cells within the lungs, including
      neutrophils and capillary endothelial cells. Cellular activation during innate
      immune responses is mediated in part by tumor necrosis factor-alpha (TNF-alpha)
      and interleukin (IL)-1-initiated signaling through their receptors, activation of
      nuclear factor kappa B (NF-kappaB) and downstream gene transcription, endothelial
      cell signaling initiated by neutrophil adherence to intercellular adhesion
      molecule (ICAM)-1, and binding of leukocyte adhesion molecules to cellular and
      matrix ligands. These events are essential to effective host defense during
      pneumonia.

PMID- 16088448
TI  - Host defense and bacterial pneumonia.
AB  - Despite advances in antibiotic therapy, bacterial pneumonia remains a significant
      cause of morbidity and mortality. Pulmonary host defense has both an innate
      component, consisting of nonspecific antimicrobial factors, as well as an
      acquired component, which is pathogen-specific. Defects in either arm of the
      immune system can have a profound impact on the other because these are highly
      interactive systems. From the upper airway to the respiratory alveolus, defense
      mechanisms are in place to maintain sterility of the lower respiratory tract.
      These features include anatomical barriers, nonspecific antimicrobial peptides,
      the mucociliary escalator, and the airway lining fluid. In the airspaces, the
      alveolar macrophage is the cell responsible for early pathogen clearance and
      subsequent initiation of the acute inflammatory response. Neutrophil recruitment
      and acquired immune responses are dependent on cytokine secretion by these
      resident tissue phagocytes. This article reviews the salient features of innate
      and acquired immunity against bacterial pathogens and how host factors (such as
      alcoholism) undermine these antibacterial defenses.

PMID- 16088449
TI  - Immunity against mycobacteria.
AB  - Mycobacterium tuberculosis is the most prevalent infectious pathogen in the
      world, largely due to its unique interactions with the human immune system. Even
      in a normal host, a frequent outcome of infection with M. tuberculosis is failure
      to completely eradicate the organisms, despite the development of cell-mediated
      immunity. Viable organisms persist in a state in which they do not progressively
      replicate, leading to latent infection, which carries a risk of breakdown into
      active (reactivation) tuberculosis at some point later in life. Key features of
      the immune response against mycobacteria are reviewed here, and potential
      mechanisms by which the organisms may subvert these host defenses are discussed.
      Despite the multicellular nature of the host response to infecting mycobacteria,
      the organisms cannot be eradicated and contribute to the ongoing worldwide
      epidemic with tuberculosis.

PMID- 16088450
TI  - Pulmonary defenses against fungi.
AB  - Pulmonary immunity to fungal pathogens requires both innate and adaptive immune
      responses. Alveolar macrophages, dendritic cells, and neutrophils are the
      phagocytic cells of the lung innate system. These cells produce early
      inflammatory mediators (i.e., reactive oxygen species, cytokines, and chemokines)
      in response to fungal infection. The production of early cytokines by innate
      cells, namely tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-12,
      plays a central role in the development of protective cell-mediated immunity
      against fungi. T helper 1 (Th1) cell-mediated immunity is essential for limiting
      a pulmonary fungal infection. Virulence factors produced by the fungi can also
      modulate the host immune response. Fungal virulence factors include the
      production of prostaglandins and a polysaccharide capsule. The type of adaptive
      immune response (T1 vs T2) generated determines whether the fungi are cleared
      from the lungs or a chronic fungal infection prevails.

PMID- 16088451
TI  - Failure of host defenses in human immunodeficiency virus.
AB  - Infection with human immunodeficiency virus (HIV) creates systemic
      immunosuppression but induces unique alteration of immune functions within lung
      tissue as well. Cells within the lung, particularly the alveolar macrophage, are
      important reservoirs of HIV infection. The body's immune response to HIV-infected
      lung cells creates a persistent inflammatory environment within the alveolar
      space, which compromises host responses to infectious pathogens. HIV infection
      alters mucociliary function as well as critical components of airway secretions.
      Within lung parenchyma, innate and adaptive immune responses to inhaled
      microorganisms are impaired, including neutrophil influx, lymphocyte responses,
      and humoral immunity. Collectively, these HIV-induced alterations of host defense
      explain the increased susceptibility of HIV-infected persons for oropharyngeal
      candidiasis, bacterial pneumonia, and Pneumocystis jiroveci pneumonia.

PMID- 16088452
TI  - Sepsis and the lung host response.
AB  - Sepsis is the leading cause of death in critically ill patients and is the most
      common risk factor for the development of acute lung injury in medical patients.
      Initially investigators hypothesized that an excessive proinflammatory response
      contributed to the pathogenesis of sepsis. However, this hypothesis overlooked
      the beneficial effects of proinflammatory mediators and the detrimental effects
      of an excessive anti-inflammatory response. This has led to a new hypothesis
      where sepsis is characterized by imbalances of the pro- and anti-inflammatory
      responses, with tissue injury the result of an excessive proinflammatory response
      and impaired pulmonary host defense the result of an excessive anti-inflammatory
      response. This article reviews clinical studies and animal models which show that
      sepsis results in an impaired lung host response to bacteria. Information in this
      article should provide the reader with an increased understanding of the
      pathogenesis of sepsis and the realization that new therapeutic strategies for
      sepsis need to take into account the need to balance pro- and anti-inflammatory
      responses to maintain pulmonary host defenses and prevent the development of
      acute lung injury.

PMID- 16088453
TI  - Immunomodulation for the prevention and treatment of lung infections.
AB  - The clearance of microbes from the respiratory tract requires the generation of a
      vigorous and compartmentalized host immune response. When pulmonary infection
      occurs in the setting of impaired innate and acquired immune responses,
      antimicrobial agents alone often cannot cure the host. This article reviews both
      conventional and experimental approaches to stimulate innate and acquired immune
      responses. These strategies include immunotherapy to directly enhance effector
      cell function of phagocytic cells (e.g., cytokine immunotherapy) or skew immune
      responses toward protective type 1 immunity (e.g., CD40 ligand, CpG
      dinucleotides, cytokines). Additionally, the role of immunization (either active
      or passive) in the prevention and treatment of respiratory tract infection is
      addressed. Although the clinical context in which these immunomodulatory
      approaches may be of benefit in the treatment of respiratory tract infection
      remains uncertain, potential applications of immunotherapy are explored.

PMID- 16088455
TI  - Blastomycosis.
AB  - Blastomycosis is an endemic fungal infection predominantly seen in the south
      central and mid-western United States and portions of Canada. The disorder is
      caused by Blastomyces dermatitidis, a dimorphic organism usually acquired through
      inhalation of aerosolized conidia. Most acutely infected patients are
      asymptomatic or develop a self-limited respiratory illness. Chronic pneumonia is
      the dominant clinical manifestation of blastomycosis, although extrapulmonary
      disease is common, usually involving skin and subcutaneous tissue, bones and
      joints, the prostate gland, and the central nervous system (CNS). Chronic
      blastomycosis should always be treated with systemic antifungal therapy, and oral
      itraconazole is the drug of choice for mild to moderate forms of the disease.
      Severe manifestations, including adult respiratory distress syndrome, CNS
      involvement, and disease in severely immunocompromised hosts require primary
      therapy with an amphotericin B formulation. There are no routine measures to
      prevent blastomycosis, although there is promising experimental data involving
      the use of a live, attenuated vaccine.

PMID- 16088456
TI  - Coccidioidomycosis.
AB  - Coccidioidomycosis is a fungal infection caused by Coccidiodes. The fungus has a
      limited geographic distribution but the disease can be seen anywhere. Primary
      infection is usually self-limited; however, when a large dose of fungus is
      inhaled or in an immunosuppressed host, the patient may develop overwhelming
      infection, including ARDS, in a brief period. While serodiagnosis can help to
      suspect the diagnosis, particularly in the setting of overwhelming disease,
      diagnostic efforts should focus on identifying the organism in body fluids or
      tissues. Several treatment options are available. Amphotericin B was the drug of
      choice for decades when there were no alternatives. Triazoles, fluconazole and
      itraconazole, are very effective and much less toxic.

PMID- 16088457
TI  - Pulmonary histoplasmosis syndromes: recognition, diagnosis, and management.
AB  - Pulmonary manifestations are the hallmark of histoplasmosis. Clinical syndromes
      range from asymptomatic infection to diffuse alveolar disease causing respiratory
      difficulty and even death. Serologic tests for antibodies and antigen detection
      are especially helpful in the diagnosis of histoplasmosis but are frequently
      overlooked. Detection of Histoplasma capsulatum antigen in bronchoalveolar lavage
      fluid may be particularly helpful in patients with acute pulmonary histoplasmosis
      or disseminated disease with pulmonary involvement. Topics of special importance
      for pulmonary disease specialists include the approach to the exclusion of
      histoplasmosis in the evaluation of patients with suspected sarcoidosis,
      differentiation of pulmonary histoplasmosis and malignancy in those with lung
      masses or mediastinal lymphadenopathy, and recognition and management of chronic
      pulmonary and mediastinal manifestations of histoplasmosis. Although
      histoplasmosis is mild and self-limited in most healthy individuals, antifungal
      therapy is indicated in those with acute diffuse pulmonary infection, chronic
      pulmonary histoplasmosis, progressive disseminated disease, and perhaps
      mediastinal adenitis accompanied by obstructive symptoms. Antifungal therapy to
      prevent reactivation of histoplasmosis during immunosuppressive therapy, or
      transition of mediastinal adenitis to fibrosing mediastinitis, although
      controversial, is not recommended. Several new drugs active against H. capsulatum
      offer alternatives in patients failing or intolerant of current therapies.

PMID- 16088458
TI  - Pulmonary cryptococcosis.
AB  - Pulmonary cryptococcosis is the consequence of the inhalation of Cryptococcus
      neoformans, an encapsulated yeast, from various environmental sources. It is
      commonly accepted that the acquisition of the disease occurs early in life and
      that the disease is mostly related to a reactivation from a pulmonary site in
      immunocompromised hosts such as patients infected with human immunodeficiency
      virus. Clinical and radiological presentations of the disease are nonspecific and
      are more severe in immunocompromised hosts with acquired immunodeficiency
      syndrome (AIDS). However, fulminant forms have also been reported in apparently
      immunocompetent hosts. C. neoformans has rarely been responsible for colonization
      of the respiratory tract; this usually occurs in immunocompetent hosts with
      preexisting pulmonary disease. Diagnosis of pneumonia is obtained by either
      analysis of bronchoalveolar lavage in AIDS patients or by the
      histology/mycological analysis of a pulmonary nodule. In any case, a careful work
      up for diagnosing dissemination should always be performed. Antifungal treatment
      has to be given in most of the immunocompetent hosts and always in those with any
      kind of immunodeficiency with isolated pulmonary cryptococcosis.

PMID- 16088459
TI  - Fusarium infections in critically ill patients.
AB  - Invasive mold infections (IMIs) are significant causes of infectious mortality in
      immunocompromised patients, such as those with hematologic malignancies and
      allogeneic bone marrow transplant recipients. Of the IMIs, invasive aspergillosis
      is by far the most common. Nevertheless, over the past decade, other filamentous
      molds, such as Fusarium species, have been increasingly reported as the cause of
      severe IMIs in these patient populations. Herein we critically review the
      epidemiology, pathogenesis, clinical presentation, diagnostic methods, and
      therapeutic approaches for invasive fusariosis in immunocompromised hosts. We
      also present the key characteristics and differentiating features of invasive
      fusariosis and invasive aspergillosis. Current therapeutic approaches for
      fusariosis are suboptimal, resulting in exceedingly high mortality rates. At
      present, prompt diagnosis along with rapid initiation of appropriate treatment
      and, more importantly, reconstitution of the host immune responses are critical
      for a favorable outcome of this devastating opportunistic mycosis.

PMID- 16088461
TI  - Dematiaceous fungi.
AB  - Dematiaceous fungi are the etiologic agents of phaeohyphomycosis and are
      increasingly recognized as causing disease in humans. A wide variety of
      infectious syndromes are seen, from local infections due to trauma to widely
      disseminated infection in immunocompromised patients. Pulmonary disease may be
      divided into allergic bronchopulmonary and nonallergic syndromes, depending on
      the species. These fungi have unique pathogenic mechanisms owing to the presence
      of melanin in their cell walls, which imparts the characteristic dark color to
      their spores and hyphae. Melanin is a known virulence factor in certain fungi,
      including Cryptococcus neoformans and Wangiella dermatitidis. Therapy depends
      upon the clinical syndrome. Local infection may be cured with excision alone,
      whereas systemic disease is often refractory to therapy. Azoles such as
      itraconazole and voriconazole have the most consistent in vitro activity, though
      there is more clinical experience with itraconazole. Further studies are needed
      to better understand the pathogenesis and treatment of these uncommon infections.

PMID- 16088460
TI  - Scedosporium/Pseudallescheria infections.
AB  - The genus Scedosporium comprises a group of filamentous fungi found ubiquitously
      in the environment. The two major human pathogens within this genus are S.
      apiospermum-the asexual state of Pseudallescheria boydii-and S. prolificans. Both
      histologically resemble Aspergillus species, with hyphae that are septated and
      branching at acute angles. Although Scedosporium infections can occur in
      immunocompetent persons, the overall incidence has increased over the last decade
      as a consequence of improved diagnostics and a growing immunosuppressed
      population (e.g., transplant, malignancy, acquired immunodeficiency syndrome).
      These organisms can cause systemic infection in immunocompromised hosts
      manifested as sinopulmonary, central nervous system, osteoarticular, ocular,
      endovascular, and lymphocutaneous disease. Dissemination may occur hematogenously
      or contiguously, with high associated mortality (>75%). Scedosporium species are
      known to be largely resistant to traditional antifungals such as amphotericin B;
      however, treatment with newer triazoles, such as voriconazole, appears to be more
      efficacious.

PMID- 16088462
TI  - Invasive pulmonary aspergillosis.
AB  - Invasive pulmonary aspergillosis (IPA) is the most common fungal pulmonary
      infection in severely immunocompromised patients. Aspergillus species are
      commonly isolated from the soil, plant debris, and the indoor environment,
      including the hospital. Phagocytosis is the main host defense against Aspergillus
      conidia and hyphae. The diagnosis of IPA is based on clinical, radiological, and
      mycological data. Clinical signs have a low specificity. The most typical
      computed tomographic (CT) findings are nodules with or without the halo sign or
      the air crescent sign. Sensitivity of microscopy and culture of noninvasive
      collected samples is low. Galactomannan and nucleic acid detection in serum or in
      bronchoalveolar lavage (BAL) fluid help to confirm the diagnosis. Crude mortality
      is high and strongly correlated with the underlying condition, stage of the
      underlying disease, and extension of the aspergillosis. Optimal therapeutic
      strategies include the prevention of contamination in patients at high risk,
      early initiation of antifungal therapy, surgery in some instances, and,
      importantly, treatment of the underlying condition to restore whenever possible a
      certain degree of immunocompetence. Voriconazole has demonstrated better efficacy
      and safety than amphotericin B deoxycholate. The improved survival observed with
      voriconazole makes it a new reference for the first-line therapy of IA. Lipid
      formulations of amphotericin B, caspofungin, micafungin, and posaconazole are
      other therapeutic options in the event of failure of or contraindication to
      voriconazole. The main indication for surgery is prevention of severe hemoptysis
      when the lesion is adjacent to a large vessel.

PMID- 16088463
TI  - Noninvasive Aspergillus pulmonary disease.
AB  - Noninvasive Aspergillus pulmonary disease may be the result of a host response to
      Aspergillus antigens or colonization of the lung with Aspergillus species. The
      prototype example of each of these phenomena are allergic bronchopulmonary
      aspergillosis and aspergilloma. Allergic bronchopulmonary aspergillosis is a form
      of asthma associated with a Type I, III, and IV allergic response to Aspergillus
      antigens. It presents clinically as asthma but is also associated with
      bronchiectasis, airway destruction, and permanent lung injury if inadequately
      treated. Treatment consists of anti-inflammatory agents such as corticosteroids.
      Antifungal agents may also be useful to lower the fungal antigen load.
      Aspergillomas grow in areas of devitalized lung. They may manifest as
      asymptomatic radiographic abnormalities. The concern is that they may lead to
      hemoptysis that can be life threatening. Definitive treatment is surgical
      resection, but this is often prohibited because these patients often have
      inadequate lung function to tolerate thoracic surgery. Other treatment options
      include azoles and percutaneous instillation of antifungals.

PMID- 16088464
TI  - Zygomycosis.
AB  - Zygomycosis is an invasive mycotic disease caused by fungi in the class
      Zygomycetes. Within this class, the most common species associated with infection
      include Absidia corymbifera, Apophysomyces elegans, Cunninghamella bertholletiae,
      Rhizomucor pusillus, Rhizopus microsporus var. rhizopodiformis, and Rhizopus
      arrhizus. These fungi all produce characteristic hyphal forms in tissue that are
      variable in width, produce haphazard branching, and lack septation. Although
      these fungi are ubiquitous in the environment, they are opportunists causing
      invasive disease in compromised hosts with a high mortality even when aggressive
      antifungal therapy and surgical intervention are utilized. Clinically, the
      disease most often affects the sinus with or without pulmonary involvement;
      direct extension from sinuses into cerebral tissue is not uncommon. This article
      describes the general clinical features of zygomycosis, with an emphasis on
      management in the setting of immunosuppression.

PMID- 16088465
TI  - New antifungal agents.
AB  - Two new antifungal agents, voriconazole and caspofungin, are now available for
      treatment of systemic fungal infections. Voriconazole is an extended-spectrum
      triazole that is fungicidal for filamentous fungi, including Aspergillus,
      Scedosporium, Fusarium, Paecilomyces, and is active against all species of
      Candida. It has become first-line therapy for invasive aspergillosis.
      Voriconazole is given either by the oral or the intravenous route. Clinicians
      must be aware of drug-drug interactions and side effects, including visual
      disturbances and photosensitivity rash that can occur when voriconazole is used.
      Caspofungin is the first drug available from a new class of antifungal agents,
      echinocandins, that act to inhibit fungal cell wall synthesis. Caspofungin is
      fungicidal for all species of Candida and more slowly kills Aspergillus species.
      Caspofungin, available only for intravenous administration, has minimal side
      effects and very few drug interactions. The echinocandins will find most use for
      Candida infections and as second-line therapy for Aspergillus infections.

PMID- 16088466
TI  - Tuberculosis and other mycobacterial infections.

PMID- 16088467
TI  - Tuberculosis as a major global health problem in the 21st century: a WHO
      perspective.
AB  - The World Health Organization, the Global Partnership to Stop TB, and the
      Millenium Development Project have all adopted the following 2005 targets for
      tuberculosis control: to detect at least 70% of all estimated sputum smear
      positive cases and to treat successfully at least 85% of them. Although
      implementation of the DOTS strategy is the foundation for proper tuberculosis
      control, basic DOTS implementation may not be enough to reach these targets.
      Instead, evidence from several countries indicates that, although cure rates are
      approaching the global target, the case detection target may not be met, even
      with 100% DOTS implementation in designated public facilities. Thus, tuberculosis
      control must be critically examined to foster higher performance. In the context
      of an expanded framework for tuberculosis control, we present four strategic
      interventions through which cure and case detection rates may be significantly
      improved: (1) wider involvement of community workers, (2) engagement of private
      practitioners, (3) proper management of drug-resistant tuberculosis, and (4)
      efforts focused on controlling tuberculosis and human immunodeficiency virus. We
      conclude that, although country-based estimates need further refinement to
      ascertain the impact of each intervention, a fundamental shift in the approach to
      tuberculosis control is required if the global targets are to be reached rapidly.

PMID- 16088468
TI  - The Arden House Conference on Tuberculosis, revisited: perspectives for
      tuberculosis elimination in the United States.
AB  - In 1959, the Arden House Conference on Tuberculosis inaugurated modern
      tuberculosis control strategy by declaring that curative treatment of
      tuberculosis is a public health obligation. In the decades after the conference,
      tuberculosis rates decreased more slowly than forecast, perhaps because
      chemotherapy had less impact than anticipated, or because the conference's
      recommendations were not implemented fully until 30 years later, when an epidemic
      resurgence jolted the country out of complacency. Since 1959, several broad
      issues have gained prominence after being overlooked or unexpected at the time of
      the Arden House Conference. These include tuberculosis outbreaks, contact
      investigations, treatment of latent Mycobacterium tuberculosis infection, briefer
      treatment regimens, human immunodeficiency virus infection, bacteriology
      laboratory capabilities, and transnational migration. Trends and experience have
      shown that tuberculosis elimination in the United States will be unfeasible until
      both technological advances and social justice allow control systems to be
      applied throughout the world.

PMID- 16088469
TI  - Leprosy of the past and today.
AB  - Despite enhanced disease control efforts, leprosy remains an important cause of
      disability in several countries. Being based on case detection, the exact
      prevalence of the disease is not easily estimated. Currently around 600,000 new
      cases are treated annually. Advances in immunology and molecular biology have led
      to a greater understanding of the disease and to hopes for improved diagnostic
      tests and vaccination strategies. The major advance, though, is the development
      of highly effective combination drug regimens which, provided all doses are
      taken, rarely fails to cure. The challenge to leprosy control services is to
      overcome the stigma associated with the disease so that patients present with
      minimal lesions and before disabilities have developed. Although it is hoped that
      leprosy as a serious public health problem will be eliminated within a few years,
      continuing care for those suffering from deformity and rejection by society will
      be required for several decades.

PMID- 16088470
TI  - Mycobacterial infections caused by nontuberculous mycobacteria.
AB  - The purpose of this review is to familiarize a broad range of medical
      professionals with a relatively new and growing problem of infections caused by
      mycobacteria other than M. tuberculosis and M. leprae. There are at least 60
      mycobacterial species that have been identified as causative agents of diseases
      in humans. They are all environmental bacteria, and they are not transmitted from
      person to person. The usual source of infection is water, soil, and aerosols
      developed from these sources. The probability of contracting such a disease
      depends not only on the closeness of interaction with an environment containing
      an enhanced concentration of bacteria but also and foremost on the sensitivity of
      an individual to these infections, which may depend on the state of immunity and
      other so-called predisposing conditions. Therefore, these infections are often
      referred to as opportunistic, and the group of organisms causing them are usually
      referred to as nontuberculous mycobacteria (NTM). This review addresses in a
      condensed form various aspects of these infections, including bacteriology,
      clinical manifestations, diagnosis, and therapy. The reader will be able to find
      more details on each of these topics in several reviews and some original papers
      cited in this article.

PMID- 16088471
TI  - Tuberculosis transmission based on molecular epidemiologic research.
AB  - Molecular genotyping techniques developed during the past decade and conventional
      epidemiological methods have been used synergistically in studies of the
      transmission and pathogenesis of Mycobacterium tuberculosis. Research studies
      assessing contacts and outbreaks, risk factors for ongoing transmission, and
      exogenous reinfection with M. tuberculosis have advanced with applied molecular
      epidemiologic techniques. In addition, molecular epidemiologic approaches have
      enabled scientists to assess the impact of drug resistance on the transmission
      and pathogenesis of M. tuberculosis and to identify strains with broad temporal
      and spatial distributions. In the near future, the intersection of molecular
      epidemiology, bacterial population genetics, comparative genomics, immunology,
      and other disciplines will further our understanding of tuberculosis transmission
      and pathogenesis, contributing to the development of effective drugs and a
      vaccine against this important human pathogen.

PMID- 16088472
TI  - Antimicrobial therapy of tuberculosis: justification for currently recommended
      treatment regimens.
AB  - Prevention of drug resistance became the most important aim following the first
      clinical trial on streptomycin with a randomized intake in 1948. The occurrence
      of resistance was reduced by combined therapy with streptomycin and p
      aminosalicylic acid and prevented by an initial phase with three drugs. Following
      the Madras comparison of domiciliary and sanatorium therapy, chemotherapy for the
      whole world became available, but there remained the problem of compliance during
      1 year of treatment. Solutions were sought by the use of intermittently
      supervised drug administration, and in 1970, by the inclusion of the two major
      sterilizing drugs rifampicin and pyrazinamide, in regimens lasting only 6 months.
      The next 15 years were devoted to defining modern regimens, the first with a four
      drug initial phase and rifampicin throughout (2EHRZ/4RH), and the second with a
      continuation phase of ethambutol and isoniazid (2EHRZ/6EH). Considering
      individual drugs, rifampicin and pyrazinamide provide almost all of the
      bactericidal activity, whereas isoniazid is bactericidal only during the first 2
      days and thereafter prevents the emergence of drug resistance. Although models in
      vitro and in the mouse suggest that drug efficacy is related to area under the
      concentration-time curve/minimal inhibitory concentration (AUC/MIC), clinical
      trials with intermittent regimens indicate that this relationship is not present
      during human therapy.

PMID- 16088473
TI  - Latent tuberculosis infection.
AB  - Latent tuberculosis infection (LTBI) is a clinical condition characterized by a
      positive tuberculin skin test in the absence of clinical or radiological signs of
      active tuberculosis disease. It has been estimated that one third of the world's
      population is latently infected with Mycobacterium tuberculosis and serves as an
      enormous reservoir for future cases of active tuberculosis. The detection and
      treatment of individuals with LTBI and a high risk of progression to active
      tuberculosis are effective means to control the spread of tuberculosis.
      Furthermore, a better understanding of the host-pathogen interactions that result
      in latent infection could provide important insights for future drug or vaccine
      development. This chapter reviews recent developments in the molecular genetics,
      natural history, diagnosis, and treatment of LTBI within its historical context,
      including the impact of human immunodeficiency virus infection. Current treatment
      recommendations are also summarized.

PMID- 16088474
TI  - Tuberculosis and HIV/AIDS: epidemiological and clinical aspects (world
      perspective).
AB  - Human immunodeficiency virus (HIV) infection is the most powerful known risk
      factor for progression from latent infection with Mycobacterium tuberculosis to
      active tuberculosis (TB) disease. The worldwide HIV epidemic has affected TB in
      every aspect: immunopathology, epidemiology, diagnosis, treatment, and
      prevention. Of the 42 million people infected with HIV worldwide, more than a
      quarter of them are also infected with TB, and most live in countries with
      limited resources for health care in Africa and Asia. This chapter emphasizes HIV
      associated TB in resource-limited settings. TB-infected persons with HIV
      associated immunosuppression progress to TB disease at a rate of up to 10% per
      year. Standard TB diagnostic tools have diminished sensitivity in HIV co-infected
      cases. Standard TB treatment regimens may be less effective, particularly those
      that do not use a rifamycin throughout. Treatment is further complicated by
      toxicity, malabsorption, drug-drug interactions and immune reconstitution
      paradoxical reactions. TB control in the United States was destabilized in part
      by the HIV epidemic in the early 1990s; massive political will and resources were
      required to rebuild the public health infrastructure. Africa, Asia, and
      potentially the former Soviet Union are facing even greater destabilization of TB
      control due to the dual burden of disease and limited resources. An international
      response has been initiated but will require even greater political will and
      resources.

PMID- 16088475
TI  - Vaccination against tuberculosis: current status and future promise.
AB  - Tuberculosis remains a major health threat. The currently available vaccine,
      bacille Calmette-Guerin (BCG), provides insufficient protection, and multi-drug
      resistant strains are on the rise. A novel vaccine with higher efficacy is needed
      for satisfactory control of the disease. Currently, several novel vaccine
      candidates are being tested in preclinical models with promising outcome, but
      none with overwhelming success. The final decision as to whether an efficacious
      vaccine can be designed will have to await the outcome of a clinical trial
      comprising the most promising candidates identified by experimental animal
      studies.

PMID- 16088476
TI  - Tuberculosis in children.
AB  - The natural history and clinical expression of infection due to Mycobacterium
      tuberculosis differ substantially in children compared with adults. The natural
      history depends upon the age at infection and the host immune status. Children
      infected prior to age 4 have a very high rate of developing immediate clinical or
      radiographic manifestations or both, but are unlikely to develop reactivation
      disease in adulthood. In contrast, children infected in preadolescence or
      adolescence are more prone to developing more severe adult-type pulmonary
      tuberculosis soon after infection or in adulthood. It is difficult to confirm the
      diagnosis of tuberculosis by current microbiological methods. Even in
      industrialized countries, the triad of a positive tuberculin skin test,
      radiographic and/or clinical manifestations consistent with tuberculosis, and
      establishing a recent link to a known infectious case of tuberculosis is the
      "gold standard" for diagnosis. Children with tuberculosis respond well to and
      tolerate the same basic treatment regimens as used for adults. Some prevention of
      childhood tuberculosis can be achieved by the use of the bacille Calmette-Guerin
      (BCG) vaccines, but the use of chemotherapy to treat recent tuberculosis
      infection, discovered via contact tracing, is of paramount importance even when
      BCG vaccines are used.

PMID- 16088479
TI  - Endobronchial electrosurgery: argon plasma coagulation and electrocautery.
AB  - Endobronchial electrosurgery is used to remove endobronchial lesions in the
      trachea and bronchi, using either a rigid or a flexible bronchoscope. The thermal
      property of electric current is used to destroy tissue or coagulate bleeding
      sites. Electrosurgery, electrocautery, electrotherapy, and surgical diathermy are
      terms often used when referring to the use of heat for tissue destruction. In
      this article, we specifically use the term electrocautery ( EC) to describe an
      electrosurgical technique that requires probe-to-tissue contact whereby the
      conduction of electric current ionizes air resulting in tissue destruction or
      hemostasis or both. In contrast, argon plasma coagulation (APC) is a relatively
      new electrosurgical method whereby argon gas is ionized by an electric current to
      create a noncontact, homogeneous "bridge" to target tissue for coagulation or
      ablation. Both EC and APC are effective in ablating and coagulating tissue. In
      this article, we further elucidate the basic principles of electrosurgery;
      indications, complications, and techniques associated with both EC and APC; and
      how they compare with other standard endobronchial interventions, including
      mechanical debridement, laser photoresection, cryotherapy, photodynamic therapy
      (PDT), and brachytherapy.

PMID- 16088480
TI  - Endobronchial stents: past, present, and future.
AB  - Tracheobronchial prostheses, known as airway stents, are used to palliate the
      effects of large airway obstruction. The most common types of stents in current
      clinical use are made of silicone or metallic wire. An ideal stent should possess
      several characteristics: (1) it should be easy to insert and remove, if
      necessary; (2) it should be available in different sizes to match the
      obstruction; (3) once placed, it should maintain its position without migration;
      (4) it should be firm enough to resist compressive forces, yet have sufficient
      elasticity to conform to the airway contours; (5) it should be made of inert
      material, so as not to irritate the airway, precipitate infection, or promote
      granulation tissue; (6) it should exhibit the same characteristics of the normal
      airway so that mobilization of secretions is not impaired. We do not yet have an
      ideal airway stent that combines the advantages of silicone and metal stents. In
      this article, the advantages and disadvantages of currently available stents are
      reviewed, and some thoughts on the future development of airway stenting will be
      mentioned.

PMID- 16088481
TI  - Removal of self-expandable metallic stents: is it possible?
AB  - Self-expandable metallic stents (SEMS) have become an important component of the
      management of central airway disease. These stents are not, however, without
      problems and stent-related complications (SRCs) can be more formidable to treat
      than the original indication for SEMS placement. As use of SEMS has increased,
      the number of patients returning to hospital for management of SRCs has similarly
      risen. A small group of these patients will have, as their only therapeutic
      option, stent removal Thus far limited experience exists with late stent removal.
      Stent extraction is difficult and requires expertise in a variety of techniques.
      A multidisciplinary approach to both SEMS placement and extraction is strongly
      advocated.

PMID- 16088482
TI  - Diagnosis and treatment of early lung cancer: as it stands today.
AB  - Treatment of "early" stage lung cancer should offer the patient the best chance
      for cure. Disease-free survival after surgical resection of lung carcinoma in
      situ has been reported as over 90%. For "microinvasive" lung cancer it may be
      similar. After resection of stage IA non-small cell lung cancer, survival at 5
      years is approximately 60 to 70%. If endoscopic or bronchoscopic treatments of
      early stage lung cancer can offer similar disease-free survival with less
      perioperative mortality, morbidity, and cost, then they may be alternative front
      line therapies. Regardless of therapeutic choice, the initial hurdle is
      developing a practical detection method for early stage disease. This article
      reviews early stage lung cancer detection by fluorescence bronchoscopy and
      potential treatment by the endoscopic techniques of photodynamic therapy,
      brachytherapy, neodymium:yttrium-aluminum-garnet (Nd:YAG) laser, electrocautery,
      and cryotherapy.

PMID- 16088483
TI  - Endobronchial volume reduction: a myth or a marvel?
AB  - Recently, several techniques and devices have been suggested for achieving
      endobronchial volume reduction in patients with emphysema. The proposed devices
      include bronchial blockers, bronchial valves, glues, biomodulators, and stents
      for bronchial fenestration; all could be positioned only with flexible
      bronchoscopy. The current available evidence on safety and efficacy for these
      methods is based on animal studies and patient case series at best; therefore,
      all the results should be seen with caution. However, the preliminary work
      reviewed here suggests that most of the proposed techniques can work, and seem to
      be safer than surgical volume reduction. We do not yet have a proven, widely
      applicable endobronchial palliative treatment for severe emphysema, but we have a
      rapidly growing area of new research in interventional pneumology with
      preliminary results that challenge traditional medical thinking.

PMID- 16088484
TI  - Airway foreign bodies: what's new?
AB  - Tracheobronchial foreign body (FB) aspiration is a common problem in children and
      adults. The medical history is the single most predictive factor in the clinical
      suspicion of FB aspiration. The "penetration syndrome" defined by the sudden
      onset of choking and coughing with or without vomiting should prompt concerns for
      FB aspiration. Findings on radiographic imaging include visualization of a
      radiopaque FB, atelectasis, postobstructive changes, mediastinal shift, and
      pneumomediastinum. In the presence of a high clinical suspicion even with normal
      imaging studies, bronchoscopy should be performed for a thorough evaluation of
      the airways. Bronchoscopic extraction of airway FBs can be safely accomplished
      with both the rigid as well as the flexible bronchoscope in adults and children.
      Rigid bronchoscopy allows for control of the airway and provides excellent
      visualization with a variety of ancillary instruments available. Increasingly,
      both the adult and pediatric flexible bronchoscopes have been used successfully
      in the extraction of airway FBs utilizing urologic or bronchoscopic instruments.
      Airway control can be achieved with an endotracheal tube or a laryngeal mask
      airway. A delay in diagnosis increases morbidity including cough, wheeze, edema,
      and granulation tissue formation. Bronchoscopic evaluation and removal should be
      performed as soon as the diagnosis is suspected.

PMID- 16088485
TI  - Role of flexible bronchoscopy in lung transplantation.
AB  - Flexible bronchoscopy with bronchoalveolar lavage and transbronchial biopsy has
      contributed significantly to the success of lung transplantation to detect
      rejection and infections (bacterial, fungal, viral, and protozoal). It permits
      the visualization of the airway anastomosis and also allows for the management of
      airway complications using interventional bronchoscopic techniques such as
      balloon dilatation, stent insertion, and laser. A new classification (TEGLA
      [thickness, extent of injury, granulation tissue, loose sutures, anastomotic
      complications]) for uniform reporting of airway ischemic injury is proposed. The
      common complications during flexible bronchoscopy include acute hypoxemia,
      bleeding, and pneumothorax. The management of these complications during flexible
      bronchoscopy and the value of surveillance and follow-up transbronchial biopsy
      and bronchoalveolar lavage is discussed. Bronchoalveolar lavage and
      transbronchial biopsy are also used for research purposes and might hopefully
      allow recognition of bronchiolitis obliterans at an earlier stage.

PMID- 16088486
TI  - Endobronchial ultrasonography.
AB  - Endobronchial ultrasonography (EBUS) allows visualization of the tracheobronchial
      tree with real-time ultrasound and permits visualization of the internal
      structure of pulmonary lesions, which may narrow the differential diagnosis. The
      indications for EBUS are to (1) determine the depth of tumor invasion of
      tracheobronchial lesions, (2) define positional relationships with the pulmonary
      artery and veins and hilar structures and determine the extent of tumor invasion,
      (3) visualize paratracheal and peribronchial lymph nodes and metastatic lesions
      and enable EBUS-guided transbronchial needle aspiration (TBNA), and (4) localize
      and diagnose peripheral pulmonary lesions (benign or malignant). New and evolving
      applications of EBUS will increase the cost-effectiveness of EBUS in the
      diagnosis and treatment of thoracic diseases.

PMID- 16088487
TI  - Endobronchial gene therapy.
AB  - Gene therapy for pulmonary disease, a field still in the experimental stage, has
      nonetheless progressed considerably in the past decade. There have been
      significant advances in pre-clinical studies, as well as important developments
      resulting from multiple early-phase human clinical trials for a variety of
      respiratory disorders. Although there are several ways of delivering therapeutic
      genes to the lungs, the primary delivery modality remains flexible bronchoscopy.
      The flexible bronchoscope, because of its unique access to both large and small
      airways, serves as an ideal instrument to deliver therapeutic genes to the
      tracheobronchial tree, even to small airways and alveoli that are beyond the
      reach of the bronchoscope. In addition, bronchoscopic gene delivery has the
      capacity to treat pulmonary vascular disorders because delivery of marker and
      therapeutic genes via the airways has been demonstrated to successfully transduce
      the pulmonary vascular endothelium. This article describes the various methods
      and disease targets of bronchoscopically mediated gene therapy, focusing in
      particular on the results of clinical studies and providing a glimpse into the
      future of the field.

PMID- 16088488
TI  - Reprocessing the bronchoscope: the challenges.
AB  - Spread of infection through the flexible bronchoscope is underrecognized and
      underreported. Prevention of bronchoscopy-induced infection requires increased
      vigilance by the physician, assiduous implementation of reprocessing protocols,
      and closer collaboration between bronchoscopy personnel, infection control
      practitioners, and instrument manufacturers. Patient safety depends on adequate
      disinfection of bronchoscopes and accessories used, as well as proper training of
      bronchoscopists, nurses, and ancillary staff. It is important to recognize that
      microbial transmission may occur via any part of instruments or anything in
      contact with the instruments including cleaning solutions, automated washers, and
      rinsing water. Numerous surveys have suggested poor adherence to published
      preventive guidelines. To address the challenges of reprocessing bronchoscopes,
      all users must comply with guidelines for cleaning and disinfection and each
      procedure should be performed with a clean, disinfected bronchoscope.

PMID- 16088491
TI  - Epidemiology of the vasculitides.
AB  - The epidemiology of systemic vasculitis is becoming increasingly well understood.
      Giant cell arteritis is the commonest type of vasculitis with an incidence that
      is highest in populations of Scandinavian descent, where the annual incidence
      reaches 15 to 35/100,000 aged > 50 years. Takayasu's arteritis has a relatively
      uniform global incidence of one to two/million. The ANCA-associated vasculitides
      have an overall incidence of 20/million with a peak age of onset at 65 to 74
      years. Wegener's granulomatosis appears to be more common in northern Europe
      compared with microscopic polyangiitis, which seems to be more common in southern
      Europe. Henoch-Schonlein purpura is the commonest form of childhood vasculitis in
      the West with an incidence of 20/100,000 aged < 17 years, but it is much rarer in
      adults (13/million). Kawasaki disease is commonest in the childhood population of
      southeast Asia; in Japan the incidence is 500/million aged < 5 years, 50% of
      cases occur in those aged < 2 years. Behcet's disease occurs along the Silk Road
      and in the Mediterranean littoral with a prevalence in Turkey of 380/100,000. The
      various types of vasculitis have very different geographical and ethnic
      distributions, which provide clues to the pathogenesis.

PMID- 16088492
TI  - Pathogenesis of pulmonary vasculitis.
AB  - Vasculitis is inflammation of blood vessels and can affect any type of vessel in
      any organ. Pulmonary vasculitis usually is a component of a systemic small vessel
      vasculitis. Three major forms of small vessel vasculitis that often affect the
      lungs are Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss
      syndrome. These forms of vasculitis are strongly associated with antineutrophil
      cytoplasmic autoantibodies (ANCA) directed against enzymes contained in the
      primary granules of neutrophils and peroxidase-positive lysosomes of monocytes.
      This review discusses the evidence for a pathogenic role of ANCA. In vitro, ANCAs
      can activate cytokine-primed neutrophils and monocytes resulting in oxygen
      radical formation and release of lysosomal enzymes. In vivo, antimyeloperoxidase
      ANCA has been shown to induce crescentic glomerulonephritis and systemic
      vasculitis. Overall, the available data suggest that ANCA are indeed a pathogenic
      factor in the development of small-vessel vasculitis. Antiglomerular basement
      membrane (anti-GBM) disease also causes pulmonary vasculitis through immune
      attack on alveolar capillaries and glomerulonephritis through antibody mediated
      injury to glomerular capillaries. Thus, there is evidence that antibodies are
      important pathogenic factors in both ANCA disease and anti-GBM disease, however,
      there are also indications that T cells may play important pathogenic roles in
      both categories of disease as well.

PMID- 16088493
TI  - Pathology of pulmonary vasculitis.
AB  - There are three major vasculitis syndromes that affect the lung: Wegener's
      granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis
      (MPA). The pathology of pulmonary vasculitis is complicated because it requires
      correlation with clinical, laboratory, and radiological features; there is
      overlap in some histological features among the vasculitis syndromes; biopsies
      early in the course of disease or after therapy may show atypical or incomplete
      histological features; the differential diagnosis is complex and includes
      infection that should not be treated with corticosteriods or immunosupressive
      agents; and few pathologists have much experience with these cases. Major
      histological features of necrosis, granulomatous inflammation, and vasculitis
      characterize WG. The inflammatory consolidation consists of a mixture of
      neutrophils, lymphocytes, plasma cells, macrophages, giant cells, and
      eosinophils. Necrosis may take the form of neutrophil microabscesses or
      geographic necrosis. Granulomas may take several forms, including scattered or
      loose clusters of giant cells, palisading histiocytes or giant cells lining the
      border of geographic necrosis or microabscesses, and palisading microgranulomas.
      Sarcoidal granulomas are very rare. CSS may show eosinophilic pneumonia, allergic
      granulomas, and eosinophilic vasculitis. Asthmatic bronchitis may also be
      present. Biopsies from CSS patients are rare because this syndrome is usually
      diagnosed clinically. Microscopic polyangiitis demonstrates neutrophilic
      capillaritis and diffuse alveolar hemorrhage.

PMID- 16088494
TI  - Pulmonary vasculitis.
AB  - This review summarizes the radiological manifestations of the vasculitides of
      proven or presumed immunologic origin in which the inflammatory reaction is
      directed primarily against the vessel wall. These include Wegener's
      granulomatosis, Churg-Strauss syndrome, Takayasu's arteritis, Behcet's syndrome,
      Goodpasture's syndrome, and microscopic polyangiitis. Chest radiography is used
      routinely in the initial evaluation and follow-up of these patients. The
      radiographic findings however are nonspecific and need to be interpreted together
      with the clinical findings. Computed tomography (CT) plays an increasingly
      important role in the assessment of patients with vasculitis and, in the proper
      clinical context, allows a confident diagnosis of some of these entities.
      Magnetic resonance imaging and positron emission tomography play a limited role.
      The characteristic imaging manifestations of the various vasculitides are
      reviewed and illustrated.

PMID- 16088495
TI  - Wegener's granulomatosis: evolving concepts in treatment.
AB  - Wegener's granulomatosis (WG), the most common of the pulmonary granulomatous
      vasculitides, typically involves the upper respiratory tract, lower respiratory
      tract (bronchi and lung), and kidney, with varying degrees of disseminated
      vasculitis. Major histological features include a necrotizing vasculitis
      involving small vessels, extensive "geographic" necrosis, and granulomatous
      inflammation. Clinical manifestations of WG are protean; virtually any organ can
      be involved. Further, the spectrum and severity of the disease is heterogeneous,
      ranging from indolent disease involving only one site to fulminant, multiorgan
      vasculitis leading to death. The pathogenesis of WG has not been elucidated, but
      both cellular and humoral components are involved. Circulating antineutrophil
      cytoplasmic antibodies (cANCA) likely play a role in the pathogenesis and often
      correlate with activity of the disease. Treatment strategies are evolving.
      Cyclophosphamide (CYC) plus corticosteroids (CS) is the mainstay of therapy for
      generalized, multisystemic WG. Historically, the combination of CYC plus CS was
      used for a minimum of 12 months, but concern about late toxicities associated
      with CYC has led to novel treatment approaches. Currently, short-course (3-6
      months) induction treatment with CYC plus CS, followed by maintenance therapy
      with less toxic agents (e.g., methotrexate, azathioprine) is recommended.
      Further, recent studies suggest that methotrexate combined with CS may be
      adequate for limited, non-life threatening WG. The role of other immunomodulatory
      agents (including trimethoprim-sulfamethoxazole) is also explored.

PMID- 16088496
TI  - Microscopic polyangiitis.
AB  - Microscopic polyangiitis is a systemic vasculitis affecting smal-l and medium
      sized vessels and is characteristically associated with a focal and segmental
      necrotizing glomerulonephritis. It may present as a pulmonary-renal syndrome with
      rapidly progressive glomerulonephritis and alveolar hemorrhage, but the pattern
      of disease will vary according to the organ systems involved. Granulomatous
      disease of the upper or lower respiratory tract is not a feature, and its
      presence suggests the diagnosis of Wegener's granulomatosis. The etiology of the
      condition is unclear, but most patients have antineutrophil cytoplasm antibodies
      (ANCA) with specificity for either myeloperoxidase (MPO) or proteinase 3 (PR3),
      and there is increasing evidence that these may be pathogenic. Current treatment
      includes an induction phase using cyclophosphamide and steroids to attain
      remission, followed by a maintenance phase in which the levels of
      immunosuppression are gradually reduced. Azathioprine may be substituted for
      cyclophosphamide at 3 months. Adjunctive plasma exchange or intravenous
      methylprednisolone is used in the management of either or both severe renal
      disease and alveolar hemorrhage, and new evidence suggests that plasma exchange
      is more effective in recovery of renal function. Overall, 1-year survival in
      systemic vasculitis is around 85%, and up to 50% of patients relapse, although
      relapse is less common in those with MPO-ANCA. Newer therapies are being explored
      in an attempt to increase the efficacy and reduce the toxicity of treatment.

PMID- 16088497
TI  - Churg-strauss syndrome.
AB  - First described in 1951 as an allergic and granulomatous angiitis, Churg-Strauss
      syndrome (CSS) is a small-vessel vasculitis. Mean age at the time of diagnosis is
      approximately 50 years, with a sex ratio around 1. Asthma is the central feature
      of CSS and precedes the systemic manifestations in almost all cases, whereas 70%
      of the patients have maxillary sinusitis, allergic rhinitis, and/or sinus
      polyposis. General symptoms are frequent, and associated with pulmonary
      infiltrates in 38 to 77% of the patients; peripheral neuropathy, usually
      mononeuritis multiplex, in 64 to 75%; skin involvement in 40 to 70%; and
      gastrointestinal tract symptoms in 37 to 62%. Cardiac involvement is common, with
      pericarditis in 23% of the patients and myocarditis in 13%, and represents the
      primary cause of mortality. Hypereosinophilia is the main biological feature of
      CSS, whereas antineutrophil cytoplasm antibodies (ANCA), especially anti
      myeloperoxidase (MPO), are found in one third to one half of the patients.
      Triggering factors, such as vaccination, desensitization, or exposure to
      leukotriene-receptor antagonists, have been suspected as contributing to the
      development of CSS, but its etiology has not yet been fully elucidated. T-helper
      type 2 (Th2) lymphocytes, by analogy with the pathogenesis of asthma, eosinophils
      infiltrating tissues, and anti-MPO ANCA are probably implicated in the
      pathogenesis of vasculitic lesions. CSS usually responds rapidly to
      corticosteroids. Adjunction of cyclophosphamide is indicated when at least one
      factor of poor prognosis is present. With treatment, remission is obtained in
      more than 80% of the patients, but it is often impossible to withdraw
      corticosteroids completely because of residual asthma. Relapses occur in 25% of
      the patients, half during the first year. The 10-year survival rate was 79% for
      our patients, with 73% of them requiring low-dose prednisone maintenance therapy
      for persistent asthma.

PMID- 16088498
TI  - Pulmonary capillaritis.
AB  - Pulmonary capillaritis is defined as a histopathologic pattern of alveolar wall
      inflammation that leads to the disruption of the integrity of alveolar-capillary
      basement membranes and flooding of the alveoli with blood. The clinical
      presentation is that of diffuse alveolar hemorrhage (DAH). Pulmonary capillaritis
      is usually the consequence of an underlying immune-mediated process that is
      systemic in nature. Rarely, pulmonary capillaritis occurs in isolation. This
      article outlines a systematic approach to the management of patients presenting
      with DAH, and provides an overview of specific causes of pulmonary capillaritis.

PMID- 16088499
TI  - Behcet's disease.
AB  - Behcet's disease (BD) is a systemic disorder characterized by recurrent attacks
      of acute inflammation. Major symptoms are oral aphthous ulcers, uveitis, skin
      lesions, and genital ulcerations. Involvement of vessels, gastrointestinal (GI)
      tract, and central nervous system (CNS) is less frequent but is associated with a
      poor prognosis. Pulmonary complications of BD include aneurysms of the aorta,
      great vessels, or pulmonary arteries; arterial or venous thrombosis; pulmonary
      parenchymal changes; pleurisy, and intracardiac thrombosis. Hemoptysis caused by
      pulmonary artery aneurysms may lead to lethal hemorrhage. Recent advances in
      therapeutic strategies have improved the prognosis. In this review, the salient
      clinical and histopathological features of BD and treatment strategies are
      discussed.

PMID- 16088500
TI  - Large-vessel vasculitis.
AB  - The vasculitides affecting large and medium-sized vessels are heterogeneous. This
      group includes such disorders as giant cell arteritis, Takayasu's disease, and
      sarcoidosis. There are several challenges that may arise in the care of patients
      with these disorders. Diagnosis may be elusive when initially evaluating patients
      with large-vessel vasculitis. Most serologic markers are not specific, and tissue
      biopsy is often impractical. We will present data emphasizing the most common
      disease manifestations, to aid in recognition of a clinical picture suggestive of
      large-vessel vasculitis. We will also focus on the more common pulmonary
      manifestations and minimize case reports, which may not reflect the usual course
      of disease. Large cohort studies and randomized controlled trials to provide an
      evidence-based approach to therapy in these disorders are uncommon. We have
      included in this review discussion of those studies that we judged to be most
      rigorously conducted and clinically relevant. We provide guidelines for initial
      therapy, with caveats to assist in minimizing potential treatment-related
      complications and toxicities. Although monitoring of disease activity is often
      difficult, this is a most crucial element in minimizing disease and treatment
      associated morbidity and mortality.

PMID- 16088501
TI  - Advances in immunosuppressive drug therapy for use in autoimmune disease and
      systemic vasculitis.
AB  - Several recent advances in the use of immunosuppressive drugs in autoimmune
      disease are relevant to management of autoimmune pulmonary disease. Sequential
      immunosuppression combining remission induction with cyclophosphamide with less
      toxic maintenance therapy such as azathioprine, methotrexate, or mycophenolate
      mofetil is described in Wegener's granulomatosis, systemic vasculitis, and lupus.
      Less aggressive forms of diseases that have been routinely treated with
      cyclophosphamide have been treated with alternate regimens (e.g., methotrexate
      treatment of limited Wegener's granulomatosis, and mycophenolate mofetil for
      lupus). Finally, strategies to minimize severe side effects of immunosuppression
      include genetic testing for predisposition to drug toxicity and proposed
      techniques for fertility preservation during cyclophosphamide treatment. We
      review established principles of immunosuppressive drug use and focus on clinical
      trials in autoimmune diseases that illustrate therapeutic approaches which are
      likely to be applied more widely in the future. More detailed reviews of
      treatment of individual diseases will be found in elsewhere in this issue.

PMID- 16088502
TI  - Biologic immunomodulatory therapies in the vasculitic diseases.
AB  - The expanding range of biologic agents capable of modulating the immune response
      has opened up a new realm for therapeutic exploration in the vasculitic diseases.
      Partnered with increasing knowledge regarding the mechanisms of vascular
      inflammation, these agents have raised the question as to whether it may be
      possible to treat systemic vasculitis syndromes by selectively targeting pathways
      involved in disease pathogenesis. The action of these agents to directly modulate
      specific immunologic components offers the potential not only to impact disease
      activity but also to reduce the risk of morbidity that can result from currently
      available treatment options. The study of biologic therapies in the vasculitides
      must, however, be approached with caution because unanticipated effects on
      disease activity and disease-specific toxicities can occur. The only biologic
      agent that has currently been shown to have therapeutic efficacy in a systemic
      vasculitis syndrome is interferon-alpha in the treatment of hepatitis C
      associated cryoglobulinemic vasculitis. The use of biologic agents to treat other
      vasculitides remains investigational. Methodical evaluation of biologic agents
      prior to their use in general clinical practice is essential to understand their
      safety and efficacy. Rigorous, standardized investigations may also provide
      important insights into pathogenesis of the vasculitic diseases.

PMID- 16088504
TI  - Genetic epidemiology of sepsis and septic shock.
AB  - Sepsis affects more than 750,000 people each year in the United States alone,
      with a mortality rate of over 35% making it one of the leading causes of death in
      developed countries. Recent genetic analysis has provided us with several
      candidate genes, which have become the focus of genetic research in sepsis. The
      analysis of single nucleotide polymorphisms among various genes, such as those
      coding for pro- and antiinflammatory mediators, in the septic response has the
      potential to develop into prediction tools that will permit the clinician to more
      precisely determine the type of therapy that a particular patient should receive.
      However, unraveling the genetic variation in sepsis is complicated, and close
      attention must be paid to study design issues, including the selection of an
      appropriate study population and sample size and understanding gene-environment
      interactions. We must anticipate that future implementation of genetic
      information will lend itself to additional ethical dilemmas when we are faced
      with allocation of resources.

PMID- 16088505
TI  - Shock overview.
AB  - Despite improved understanding of the pathophysiology of shock and significant
      advances in technology, it remains a serious problem associated with high
      morbidity and mortality. Early treatment is essential but is hampered by the fact
      that signs and symptoms of shock appear only after the shock state is well
      established and the body's compensatory mechanisms have started to fail. Although
      the causes of shock are varied, the basic abnormality in all varieties is tissue
      and cellular dysoxia. In this overview we discuss the definition, classification
      and pathogenesis of shock in light of the recent advances in our understanding of
      its mechanisms. The epidemiology, diagnosis, and management of the various types
      of shock are also briefly discussed.

PMID- 16088507
TI  - Hematologic changes in sepsis and their therapeutic implications.
AB  - The blood and bone marrow constitute the hematologic organ system. Unlike other
      organ systems, hematologic organs are distributed in space and provide for a
      variety of seemingly unrelated functions. The hematologic system has both
      cellular and fluid-phase elements. Cellular elements include erythrocytes,
      leukocytes, and platelets; fluid phase elements include coagulation factors,
      natural antithrombotics, and proteins of the fibrinolytic system. The most common
      abnormalities of the hematologic system in patients with sepsis are anemia,
      leukocytosis, thrombocytopenia, and activation of the hemostatic system.
      Dysfunction of the hematologic organ system is an early manifestation of severe
      sepsis and is seen in virtually all patients with this disease. In concert with
      alterations in the endothelium, hematologic changes reflect both the body's
      reaction to an infectious insult as well as attempts to restore homeostasis.
      Dysfunction of the hematologic organ system can contribute to multiple organ
      dysfunctions and death. Recognizing these sepsis-associated changes and
      understanding the underlying pathophysiology are key to improving outcomes in
      patients with this deadly disease.

PMID- 16088508
TI  - Recognition and treatment of cardiogenic shock.
AB  - Cardiogenic shock has long been a difficult problem for clinicians. The most
      common cause is left ventricular pump failure after myocardial infarction, but
      other important causes include mechanical complications of infarction, right
      ventricular dysfunction, prolonged cardiopulmonary bypass, valvular disease, and
      cardiomyopathy. Cardiogenic shock is the leading cause of in-hospital death after
      myocardial infarction. Despite advances in management of heart failure and acute
      myocardial infarction, clinical outcomes had remained frustratingly poor, with
      reported mortality rates ranging from 50 to 80%. Recently, however, survival
      rates have been improving. Improved understanding of the pathophysiology of
      cardiogenic shock has led to renewed emphasis on the notion that stunned or
      hibernating myocardium may recover function with hemodynamic support and
      restoration of flow. This concept has underscored the importance of expeditious
      initiation of supportive measures to maintain blood pressure and cardiac output,
      including both medications and intraaortic balloon counterpulsation. Finally, the
      theory that coronary revascularization would be beneficial by reversing the
      vicious cycle in which ischemia causes myocardial dysfunction, which in turn
      worsens ischemia, which had been supported by an extensive body of observational
      and registry studies, has now been strongly buttressed by the results of two
      randomized, controlled trials, both of which show improved mortality with early
      revascularization for cardiogenic shock in the setting of acute infarction.

PMID- 16088509
TI  - Vasoactive drug use in septic shock.
AB  - Sepsis accounts for more than 210,000 deaths per year. Despite adequate fluid
      resuscitation the associated maldistribution of blood flow may cause an imbalance
      between oxygen delivery and demand, leading to global tissue hypoxia, shock, and,
      if not reversed, death. Vasoactive therapies including catecholamine and
      noncatecholamine vasopressors, ionotropes, and vasodilating agents aimed at
      restoring perfusion and normalizing oxygen consumption have improved outcomes in
      patients with persistent shock despite crystalloid resuscitation. In this review
      we discuss the mechanisms, clinical use, and commonly observed pitfalls of the
      most common and a few uncommon vasodilator agents used in the management of
      sepsis and septic shock.

PMID- 16088506
TI  - Methods of monitoring shock.
AB  - Intensive monitoring is a crucial component of the management of shock. However,
      there is little consensus about optimal strategies for monitoring. Although the
      pulmonary artery catheter has been widely used, conflicting data exist about the
      utility of this device. A variety of other techniques have been developed in
      hopes of providing clinically useful information about myocardial function,
      intravascular volume, and indices of organ function. In addition, there is
      evolving evidence that targeting and monitoring certain physiological goals may
      be most important early in the course of shock. In this chapter, we examine many
      of the available monitoring techniques and the evidence supporting their use.

PMID- 16088510
TI  - Fluid management in shock.
AB  - Shock is a broad category of injury to the human body caused by a variety of
      insults. Fluid resuscitation is the cornerstone of initial therapy for nearly all
      forms of shock. This article reviews the basic physiology determining body fluid
      composition, the goals of fluid resuscitation in shock, the types of fluids
      available for use, and clinical evidence for use of specific fluids based on
      etiology of the insult.

PMID- 16088511
TI  - Anaphylactic shock: pathophysiology, recognition, and treatment.
AB  - Anaphylaxis is a systemic, type I hypersensitivity reaction that often has fatal
      consequences. Anaphylaxis has a variety of causes including foods, latex, drugs,
      and hymenoptera venom. Epinephrine given early is the most important
      intervention. Adjunctive treatments include fluid therapy, H (1) and H (2)
      histamine receptor antagonists, corticosteroids, and bronchodilators; however
      these do not substitute for epinephrine. Patients with a history of anaphylaxis
      should be educated about their condition, especially with respect to trigger
      avoidance and in the correct use of epinephrine autoinjector kits. Such kits
      should be available to the sensitized patient at all times.

PMID- 16088512
TI  - Vasopressin.
AB  - Vasopressin is a hormone that is essential for both osmotic and cardiovascular
      homeostasis. A deficiency of vasopressin exists in some shock states and
      replacement of physiological levels of vasopressin can restore vascular tone.
      Vasopressin is therefore emerging as a rational therapy for vasodilatory shock.
      In this article we review the rationale and summarize the evidence for using
      vasopressin in vasodilatory shock states, such as septic shock. We then highlight
      the areas of uncertainty in using vasopressin for septic shock and summarize the
      reasons for clinical equipoise. We close by suggesting that further randomized
      controlled trials of vasopressin in septic shock are required before vasopressin
      is used routinely for management of septic shock.

PMID- 16088513
TI  - Corticosteroid therapy in patients with severe sepsis and septic shock.
AB  - Corticosteroids have been considered for decades for the treatment of severe
      sepsis and septic shock, based on their pivotal role in the stress response and
      their hemodynamic and antiinflammatory effects. Whereas short-term therapy with
      high doses of corticosteroids (up to 42 g hydrocortisone equivalent for 1-2 days)
      has been ineffective or potentially harmful, prolonged therapy with lower doses
      (200-300 mg hydrocortisone for 5-7 days or longer) in septic shock has recently
      revealed beneficial effects in several randomized, controlled trials. Assuming
      relative adrenal insufficiency (RAI) and peripheral cortisol resistance,
      treatment with low-dose hydrocortisone improved shock reversal, reduced
      inflammation, and improved outcome. Shock reversal and reduction of mortality
      were more effective in patients with RAI, and most significant in patients with
      severe shock. Diagnosis of RAI with corticotropin tests in septic shock, however,
      is highly dependent on cut-off values and definition of RAI. Thus, it is not
      clear yet which patients benefit most from low-dose hydrocortisone and if
      treatment should be restricted to patients with RAI. In addition the role of
      fludrocortisone is uncertain. Nevertheless, based on current data, low-dose
      hydrocortisone therapy should definitely be considered in vasopressor-dependent
      septic shock. This review will address some critical points.

PMID- 16088515
TI  - Multimodality therapy in the treatment of lung cancer.
AB  - Lung cancer is the leading cause of cancer death in the world, causing more than
      one million deaths each year. The incidence and mortality rates are highest in
      the United States and Europe and continue to increase in developing nations. Non
      small cell lung cancer (NSCLC) accounts for 80 to 85% of all new cases of lung
      cancer. The majority of patients with NSCLC present with advanced disease at the
      time of diagnosis. Although the prognosis of advanced NSCLC is very poor, current
      chemotherapy combinations have been shown to improve 1-year survival and quality
      of life for these patients. Approximately one third of patients with NSCLC are
      diagnosed with locally advanced disease. Although cure rates are modest and
      variable in locally advanced NSCLC, multimodality therapy (chemotherapy in
      combination with surgery or radiotherapy) has resulted in statistically
      significant improvement in 5-year survival when compared with surgery or
      radiotherapy alone. Patients with early-stage NSCLC have the best long-term
      survival rates following surgical resection; however, systemic recurrences remain
      a problem in the majority of these patients. The rationale for treating patients
      with early-stage NSCLC with combined-modality therapy (chemotherapy and surgery)
      is compelling, and several randomized trials are currently in progress. Although
      progress has been slow, when we consider the recent advances in smoking
      prevention, smoking cessation, staging classification, imaging and diagnostic
      techniques, screening and therapeutic modalities, and multidisciplinary care, as
      well as in the understanding of the molecular pathogenesis of lung cancer, the
      future, in my opinion, is very promising.

PMID- 16088516
TI  - Epidermal growth factor receptor as a therapeutic target in lung cancer.
AB  - Almost two decades of research to determine how cancer cells differ from
      noncancerous cells at the molecular level have been richly rewarding. Several
      molecular growth factors and receptors have been discovered that play a role in
      tumor development and are differentially expressed in tumor cells. In this
      regard, the structure and function of the epidermal growth factor receptor (EGFR)
      have been characterized. Efforts to develop effective anticancer therapy have
      targeted this receptor because it is critical to tumor cell proliferation,
      survival, and invasiveness. Overexpression of EGFR occurs in several epithelial
      cell tumors, including non-small cell lung cancer (NSCLC). Small-molecular-weight
      EGFR tyrosine kinase inhibitors and EGFR monoclonal antibodies are among the
      agents that have demonstrated activity against NSCLC. These compounds, which are
      designed to selectively target tumor cells, represent a new and novel treatment
      approach that is being evaluated in NSCLC clinical trials.

PMID- 16088517
TI  - Epidermal growth factor receptor inhibitors in lung cancer therapy.
AB  - Over the past decade our evolving knowledge and understanding of cancer biology
      has allowed rapid progression in the development of targeted cancer therapy.
      Improving lung cancer mortality has remained a difficult task; however,
      therapeutic agents directed against the epidermal growth factor receptor (EGFR)
      have provided physicians with a valuable new tool to integrate into multimodality
      therapy. EGFR inhibitors have been shown to elicit meaningful antitumor effects
      and quality-of-life benefits with acceptable toxicity. The rationale, utility,
      toxicity profile, and therapeutic strategy of EGFR-targeted therapy will be
      reviewed.

PMID- 16088518
TI  - Inhibition of epidermal growth factor receptor and symptom improvement in
      advanced non-small cell lung cancer.
AB  - The majority of patients with non-small cell lung cancer (NSCLC) are not
      candidates for curative resection because of advanced disease at the time of
      diagnosis. Systemic chemotherapy has been employed with modest success to provide
      symptom relief and prolonged survival for patients with this incurable disease.
      Any benefit derived from chemotherapy in this palliative setting must be balanced
      against the substantial toxicity associated with cytotoxic drugs. A novel
      approach to anticancer treatment based on specific targeting molecular processes
      has recently demonstrated efficacy. ZD1839 is a low-molecular-weight molecule
      that is capable of inhibiting epidermal growth factor receptor (EGFR)-associated
      tyrosine kinase activity. Consequently, ZD1839 interrupts EGFR-mediated
      activities such as tumor cellular proliferation, motility, survival, and
      invasiveness. In vitro and in vivo studies have shown that ZD1839 has activity
      against NSCLC. The results of ZD1839 in randomized clinical trials of patients
      with advanced NSCLC are reported in this review. In addition to evaluating
      response rates and clinical endpoints, these trials prospectively evaluated
      symptom improvement and quality of life.

PMID- 16088519
TI  - Rationale for investigation of epidermal growth factor receptor inhibitors in
      definitive treatment of locally advanced non-small cell lung cancer and head and
      neck cancer.
AB  - Designing targeted therapies has become an important field in cancer
      therapeutics. The epidermal growth factor receptor (EGFR) is a molecular target
      that has gained immense attention as preclinical and clinical studies have
      supported its potential role for therapy of a variety of cancers, including non
      small cell lung cancer (NSCLC) and head and neck (HN) cancer. Several compounds
      that specifically inhibit EGFR have been developed, including ZD1839, C225, and
      OSI-774. Interestingly, studies suggesting a potential role for EGFR inhibitors
      as an adjunct to the current combined-modality approach for therapy of NSCLC and
      HN cancer have been performed in the preclinical and clinical setting. Therefore,
      determining the potential of EGFR inhibitors to improve the efficacy of standard
      combined-modality regimens (chemotherapy/radiation therapy +/- surgery) for NSCLC
      and HN cancer patients is of the utmost importance. An overview of the rationale
      and the ongoing/proposed studies aimed at determining the role for EGFR
      inhibitors in combination with radiation therapy for NSCLC and HN cancer patients
      will be presented.

PMID- 16088520
TI  - Emerging infections in intensive care units.

PMID- 16088521
TI  - Epidemiology, prevalence, and sites of infections in intensive care units.
AB  - Patients in intensive care units (ICUs) have a higher risk of acquiring hospital
      associated infections than those in non-critical care areas. ICUs are sites of
      considerable broad-spectrum antibiotic use, and antibiotic-resistant pathogens
      are frequent. Bloodstream infections (BSIs), pneumonias, and urinary tract
      infections (UTIs) are the most common hospital-acquired infections and are most
      often associated with the use of invasive devices. They differ in importance in
      different types of ICUs. Coagulase-negative staphylococcus BSIs have recently
      increased in frequency, and enterococci have been as frequently reported as
      Staphylococcus aureus as causing BSIs in increasing numbers of U.S. ICUs. Fungal
      urinary tract sepsis has also increased. Device-associated infection rates
      represent the most useful surveillance rates for comparison between units and
      over time, but they differ considerably between ICU types. Outbreaks are common
      in ICUs. Recently, gram-negative bacilli have been reported more frequently than
      gram-positives in this setting, especially in NICUs. Considerable crude mortality
      and major costs are associated with these infections, but controversy persists
      over the degree of mortality attributable to them.

PMID- 16088522
TI  - Line sepsis in the ICU: prevention, diagnosis, and management.
AB  - Intravascular devices (IVDs) are universally employed in the intensive care unit.
      Although their use is essential for the administration of medications and IV
      fluids, they carry a substantial risk of infection, either from the device itself
      or from contamination of administered infusate. IVD-related infections lead to
      increased patient morbidity and mortality and excess costs, but they are
      preventable. The highest rates of IVD-related infection occur with central venous
      catheters (CVCs). Immunosuppression and other underlying illnesses further
      increase the risk of IVD-related infection. Coagulase-negative staphylococci,
      Staphylococcus aureus, and Candida spp. are the most frequent infecting
      organisms. The incidence of IVD-related infections may be minimized by simple
      measures, including maximal barrier precautions during CVC placement, specialized
      training for personnel placing IVDs, and use of chlorhexidine for cutaneous
      antisepsis. Management of line sepsis should include blood cultures, treatment
      with appropriate antibiotics or antifungals, and, in most cases, removal and
      culture of the IVD.

PMID- 16088523
TI  - Methicillin-resistant staphylococci and their treatment in the intensive care
      unit.
AB  - Methicillin resistance in Staphylococcus aureus (MRSA) and the coagulase-negative
      staphylococci (MRCNS) is widespread and continues to increase in prevalence,
      particularly in the health care setting. The clinical significance of methicillin
      resistance for patients with staphylococcal infections is not clear: studies in
      patients with bacteremia, pneumonia, and mediastinitis show a higher mortality
      with MRSA infection compared to methicillin-sensitive Staphylococcus aureus
      (MSSA) infection, though this may be due to underlying patient, pharmacodynamic,
      or microbiological differences. For serious methicillin-resistant staphylococcal
      infections, vancomycin-based regimens are preferred. Treatment alternatives for
      patients with severe methicillin-resistant infections who are unable to tolerate
      vancomycin include linezolid and quinupristin/dalfopristin; these agents should
      be considered second-line options, given the relative lack of clinical experience
      and the nonsignificant but consistent trends toward worse outcomes in bacteremia
      and pneumonia with these agents compared to vancomycin. For less severe
      infections, treatment options also include trimethoprim-sulfamethoxazole, or
      fluoroquinolones in combination with rifampin.

PMID- 16088524
TI  - Enterococcus: an emerging pathogen in hospitals.
AB  - Enterococci remain an important cause of nosocomial infection, particularly among
      the critically ill. Nationwide, the incidence of enterococcal infections is
      rising, with an increasing proportion caused by resistant organisms. The spread
      of vancomycin-resistant enterococci (VRE) within hospitals has been well studied
      and helps to explain the proliferation of enterococcal disease. After hospital
      admission of an individual carrying VRE, persistent colonization contributes to
      the development of a reservoir of colonized inpatients. VRE is usually spread
      patient to patient by health care workers caring for colonized individuals. To
      interrupt this phenomenon, infection control efforts including improved hand
      hygiene, use of gloves and cover gowns, and antibiotic control measures have been
      promoted. Prospective data concerning the relative benefit of each intervention
      are limited, and no consensus has emerged regarding the optimal strategy for
      limiting the dissemination of VRE. Appropriate treatment of an individual patient
      infected with VRE depends upon successful interpretation of the antibiotic
      susceptibility profile of the infecting strain. For the critically ill patient,
      an aggressive approach to diagnosis and therapy is essential. However, even the
      newest agents available to treat resistant enterococci are limited because of
      emerging resistance and toxicity.

PMID- 16088525
TI  - Pseudomonas aeruginosa infections in the intensive care unit.
AB  - Pseudomonas aeruginosa is a common and highly lethal agent of nosocomial
      infection, especially among intensive care unit patients. It is widespread in the
      environment and commonly recovered from water in nature and in hospital settings.
      P. aeruginosa is endowed with a formidable array of virulence factors that
      facilitate attachment to host cells, tissue invasion, and systemic disease. It is
      intrinsically resistant to many commonly employed antibiotics due to a complex
      variety of mechanisms briefly reviewed here. Resistance to fluoroquinolones
      appears to be increasing particularly rapidly. Recent advances in the
      understanding of the molecular biology of this organism have shed considerable
      light on its ability to form biofilms, which facilitate adherence, especially in
      cystic fibrosis patients, and confer resistance to clearance by host immune
      mechanisms and antimicrobial killing. Treatment studies have demonstrated a
      significant risk of emergence of resistance during therapy with a variety of
      agents. Several studies suggest that two drugs are better than one for therapy of
      serious infections, although dual therapy does not always prevent emergence of
      resistant strains. The sequencing of the genome will lead to new understanding of
      pathogenesis and may identify new drug targets.

PMID- 16088526
TI  - Infections due to Acinetobacter baumannii in the ICU.
AB  - Acinetobacter species are widespread environmental, nonfermentative, aerobic,
      gram-negative coccobacilli. Most infections due to this organism are
      opportunistic in nature and occur in patients who spend extended time in the
      intensive care unit (ICU) due to severe underlying disease, and who need
      prolonged therapy with mechanical ventilation and antimicrobial agents. Because
      the only factor amenable to prevention in this setting is antimicrobial therapy,
      avoidance of unnecessary antibiotics should be a high priority in management of
      such patients. Nosocomial spread of A. baumannii in the ICU setting has often
      been attributed to ventilatory equipment and to colonized nursing and respiratory
      personnel via hand transmission. In fact, the epidemiology of nosocomial
      respiratory colonization and/or infection with A. baumannii is now commonly much
      more complex due to the coexistence of epidemic cases with unrelated sporadic
      cases caused by different strains. This underscores the necessity to use
      molecular typing to improve the detection of microepidemics amenable to early
      control. Crude mortality rates of 30 to 75% have been reported for nosocomial
      infection due to Acinetobacter species, with the highest rates reported in
      ventilator-dependent patients. As with many other opportunistic gram-negative
      bacilli, increasing antibiotic resistance has hindered the therapeutic management
      of nosocomial infection due to Acinetobacter species. A. baumannii are now
      frequently resistant to most available antibacterial drugs, with some centers
      reporting up to 80% of strains resistant to all aminoglycosides. Even resistance
      to imipenem, which was for several years the most effective drug in treating
      Acinetobacter nosocomial infections, has now been described in several reports.
      Unfortunately, the unique propensity of Acinetobacter species to develop
      resistance to multiple antimicrobial agents reinforces concerns about the
      imminence of a post-antimicrobial era where no effective antibiotics will be
      available to treat this type of infection.

PMID- 16088527
TI  - Extended-spectrum beta-lactamases.
AB  - Extended-spectrum beta-lactamases, most commonly found in Klebsiella pneumoniae
      and Escherichia coli, have increased markedly in the past decade, particularly in
      the intensive care unit setting. The problem has been significant in the United
      States but is even more prevalent in parts of Latin America and Asia. These
      plasmid-mediated beta-lactamases confer resistance to broad-spectrum beta-lactam
      antibiotics, including third- and fourth-generation cephalosporins, aztreonam,
      and extended-spectrum penicillins. Other resistances, such as aminoglycoside
      resistance and trimethoprim/sulfamethoxazole resistance, are often cotransferred
      on the same plasmid. Fluoroquinolone resistance is often associated, resulting in
      an organism that is resistant to most of the usual antimicrobial options.
      Although carbapenems are currently considered the drugs of choice for these
      pathogens, widespread use of these agents may lead to other resistance problems.
      Due to limited therapeutic options, prevention and control measures are
      important. Traditional infection control measures, such as contact precautions,
      are recommended to prevent spread in intensive care units. In addition, because
      this type of antimicrobial resistance appears to be particularly influenced by
      antibiotic utilization, antibiotic control measures may also be a very important
      intervention in limiting the spread of extended-spectrum beta-lactamases.

PMID- 16088528
TI  - Stenotrophomonas maltophilia infections.
AB  - Stenotrophomonas maltophilia is a ubiquitous, gram-negative organism that causes
      hospital-acquired infections. Persons often come in contact with S. maltophilia
      through environmental water sources, including hospital tap water or faucets, and
      it has been associated with nosocomial outbreaks of infection. S. maltophilia
      often infects debilitated persons and those with underlying medical conditions,
      including immunosuppression. Manifestations of infection include pneumonia, often
      in mechanically ventilated patients, bacteremia, skin and soft tissue infection,
      urinary tract infection, and endocarditis. Treatment of S. maltophilia infection
      is difficult because the organism is resistant to a number of agents typically
      used for hospital-acquired infections. In vitro and clinical data indicate that
      trimethoprim-sulfamethoxazole is the agent of choice. Beta-lactamase inhibitors
      such as clavulanate are also active, and combination therapy may be indicated for
      certain serious infections due to S. maltophilia.

PMID- 16088529
TI  - Candidiasis in the intensive care unit.
AB  - In the last 2 decades, Candida species have progressed from infrequent pathogens
      to among the most important and frequent opportunistic microorganisms causing
      nosocomial infection in intensive care unit (ICU) patients. Medical and surgical
      ICUs have become the epicenter of the Candida epidemic. Superficial infections
      causing oropharyngeal and esophageal candidiasis are common, and, although non
      life threatening, may be refractory to conventional antifungals. In contrast,
      invasive candidiasis, candidemia, and hematogenous disseminated infections are
      associated with considerable attributable mortality. Although blood isolates of
      C. albicans remain susceptible to fluconazole, the increasing incidence of non-
      albicans Candida species with intrinsic reduced susceptibility to azoles creates
      new therapeutic challenges. Fortunately, lipid formulations of amphotericin B and
      the recently introduced echinocandin group represent new and strategic treatment
      responses to the challenge of invasive candidiasis.

PMID- 16088530
TI  - Antibiotic resistance in hospitals and intensive care units: the problem and
      potential solutions.
AB  - Antimicrobial resistance has generally increased over the past 5 decades, with
      occasional brief respites following the introduction of new antimicrobial
      classes. Resistance has been driven by bacterial genetic events, antibiotic
      pressures, and lapses in hospital hygiene. Recently promoted solutions to the
      problem of hand hygiene include use of alcohol-based hand rubs, which are time
      savers and gentler to hands than soap and water, and use of "universal gloving."
      The most effective antibiotic interventions have been restriction programs and
      provider computer-order entry. Unabated antimicrobial resistance requires use of
      surveillance cultures and contact precautions or cohort nursing for all patients
      colonized or infected by resistant strains.

PMID- 16088531
TI  - Global epidemiology of antimicrobial resistance among community-acquired and
      nosocomial pathogens: a five-year summary from the SENTRY Antimicrobial
      Surveillance Program (1997-2001).
AB  - Resistance to antimicrobial agents among clinically important pathogens in the
      community and hospital settings has compromised therapy and requires constant
      monitoring of emerging patterns. Although local information indexed by hospital
      service or ward remains preferred, the initiation of several comprehensive
      surveillance programs (SENTRY Antimicrobial Surveillance Program, MYSTIC
      Programme, ICARE, EARSS, etc.) offers quality susceptibility testing results to
      guide empirical treatment regimens. Enterococci and staphylococci with novel
      resistance mechanisms to glycopeptides (vancomycin, teicoplanin) require greater
      use of quinupristin/dalfopristin and linezolid. For streptococci, recent
      modifications of laboratory interpretive criteria for cefotaxime, ceftriaxone,
      and cefepime indicates that coverage remains at > or = 95%. Extended-spectrum
      beta-lactamases in Enterobacteriaceae and multidrug resistance in Acinetobacter
      spp. and Pseudomonas aeruginosa most challenge our choices of effective agents
      for nosocomial infections. Few new drugs have surfaced for therapy of these gram
      negative bacilli, and two- or three-agent combination regimens may be required
      with greater frequency, especially to cover the more prevalent resistances among
      both gram-positive cocci and gram-negative nonfermentative rods.

PMID- 16088532
TI  - Genetics of pulmonary disorders.

PMID- 16088533
TI  - Genetic epidemiological approaches to the study of lung disease.
AB  - The DNA sequence data provided by the Human Genome Project offer great promise in
      the prevention and treatment of lung disease in the new millennium. Making sense
      of these data with regard to how they relate to disease susceptibility and
      progression will require new and innovative genetic epidemiological approaches.
      Although tried and true methodologies such as case-control comparisons are still
      useful, a better understanding of genotype-phenotype relationships in lung
      disease can be gained by comparisons across similar diseases, such as the HLA
      DPB1 associations observed in both berylliosis and sarcoidosis. Study of gene
      environment and gene-gene interactions in lung disease is critical to the
      understanding of pathogenic processes in the lung such as localized inflammation
      and malignant transformation. Oligonucleotide microarray studies of gene
      expression in the lung are well under way and promise to uncover numerous
      previously unknown genetic factors involved in lung pathogenesis. One of the
      greatest challenges facing genetic epidemiologists studying lung disease in the
      new millennium will be how to translate the myriad results from microarray and
      similar data-driven technologies into information useful to the medicine
      practiced in pulmonary clinics.

PMID- 16088534
TI  - Genetics of chronic obstructive pulmonary disease.
AB  - Variability in the susceptibility to develop chronic obstructive pulmonary
      disease (COPD) is related to both genetic and environmental factors. COPD is
      likely a genetically complex disease, but severe alpha 1-antitrypsin (AAT)
      deficiency [e.g., protease inhibitor (PI) Z] remains the only proven genetic risk
      factor for COPD. Even among PI Z individuals, substantial variability in lung
      function is observed, suggesting that genetic modifiers may influence the
      expression of lung disease in severe AAT deficiency. The variable development of
      COPD in smokers without alpha 1-antitrypsin deficiency and the familial
      aggregation of lung function measurements also suggest the presence of genetic
      influences on lung function growth and decline leading to COPD. Many candidate
      gene loci have been investigated as potential COPD genetic determinants by case
      control genetic association studies. However, inconsistent results of these
      association studies have been frequent. Genetic heterogeneity and population
      stratification are two potential reasons for the conflicting findings between
      association studies. Linkage analysis studies have recently been published that
      may identify regions of the genome that contain COPD susceptibility genes. Future
      investigations of genetic influences in COPD should consider the use of family
      based designs for association studies and the study of positional candidate genes
      within regions of linkage.

PMID- 16088535
TI  - Genetics of acute respiratory distress syndrome: challenges, approaches,
      surfactant proteins as candidate genes.
AB  - There are challenges "inherent" in studying the genetics of a complex disease,
      such as acute respiratory distress syndrome (ARDS). It is necessary to define
      each ARDS subgroup using considerably narrower definitions that better reflect
      the particular subgroup. ARDS consists of several phenotypic subgroups, and
      findings from one subgroup may not be applicable to another. By extension,
      different treatment therapies may be appropriate for each phenotypic subgroup.
      This article presents the findings of a small pilot case-control association
      study where the surfactant proteins were used as candidate genes in the study of
      ARDS. This article discusses the relevance of surfactant protein genes in ARDS as
      well as the significance of genetic variants associated with ARDS subgroups.

PMID- 16088536
TI  - Genetic factors modify the risk of developing beryllium disease.
AB  - Chronic beryllium disease (CBD) is a debilitating, granulomatous lung disease
      that occurs in 1 to 5% of exposed workers. Beryllium stimulates a major
      histocompatibility Class II-restricted, TH1, CD4+ T cell-mediated immune
      response. The immunological component of the illness, coupled with the small
      subset of beryllium workers who develop disease, led researchers to hypothesize
      that genetic factors modify risk of disease. Analysis of human leukocyte antigen
      (HLA) genes, the T cell receptor, and tumor necrosis factor (TNF)-alpha focused
      on three critical steps in the development of beryllium specific immunity.
      Molecular epidemiological analysis of the association of HLA-DP, -DR, and -DQ has
      implicated HLA-DPB1E69 allelic variants in disease; however, its role in
      sensitization is unclear. A single report suggested association between HLA
      DQB1G86 and progression from sensitization to disease. A beryllium-specific
      binding motif was identified in CBD-derived T cell clones. Beryllium-stimulated
      proliferation using HLA-DPB1*0201 and TCRAV22S1/TCRBVb3 T cell receptors (TCRs)
      confirmed beryllium specificity of these molecules. The G/A transition at -308 in
      the TNF-alpha promoter was associated with high concentrations of TNF-alpha in
      bronchoalveolar lavage and to disease severity. Although these studies are
      continuing, the data confirm the role of genetic factors in the cellular response
      to beryllium.

PMID- 16088537
TI  - Genetics of idiopathic disseminated bronchiectasis.
AB  - Bronchiectasis is an abnormal dilation of bronchi, consequent to the destruction
      of their walls. It is included in the category of obstructive pulmonary diseases,
      along with chronic obstructive pulmonary disease (COPD), asthma, and cystic
      fibrosis. In approximately 50% of cases, bronchiectasis is associated with
      underlying conditions; in the remainder, known causes are not ascertainable
      (idiopathic bronchiectasis). A search for genetic determinants of this phenotype,
      with the cystic fibrosis gene as a candidate, has been performed by three
      independent groups. The results of this search agreed on the association of
      bronchiectasis with cystic fibrosis gene mutations and polymorphisms. The cystic
      fibrosis gene is also associated with bronchiectasis due to rheumatoid arthritis
      and allergic bronchopulmonary aspergillosis. A few other genes have been
      investigated in idiopathic bronchiectasis, with negative results. Idiopathic
      bronchiectasis is, therefore, to be considered as an obstructive multifactorial
      disorder belonging to the category of cystic fibrosis monosymptomatic diseases
      (or CFTR-opathies), whose pathogenesis is influenced by environmental factors and
      other undetermined genes.

PMID- 16088538
TI  - Genetics of environmental asthma.
AB  - The prevalence of asthma continues to increase throughout Western societies and
      now is estimated to affect nearly 10% of Americans. Asthma is a syndrome that
      results when a genetically susceptible individual is exposed to specific
      allergens, which triggers airway inflammation, bronchial hyperresponsiveness, and
      airway remodeling. Family and twin studies have shown that there is a major
      genetic component to the development of asthma and have attempted to determine
      the heritable risk. Linkage analysis has identified several areas of interest on
      multiple different chromosomes that have been associated with different asthma
      phenotypes. Candidate gene studies have looked at specific gene polymorphisms
      that are associated with the development of asthma. Finally, several genes are
      associated with the development of asthma in response to specific environmental
      allergen exposures. Asthma is a heterogeneous collection of diseases that can
      result from multiple different pathological processes. The inheritance of asthma
      is complex and not due to a single gene mutation. Rather, asthma appears to be
      the result of multiple genetic mutations that influence an individual's
      susceptibility to develop asthma in response to specific allergens.

PMID- 16088539
TI  - Genetic susceptibility to lung cancer.
AB  - Lung cancer is the most common cause of cancer death in the world. Environmental
      factors, particularly cigarette smoking, are of paramount importance in
      determining lung cancer risk. Lung cancer and chronic obstructive lung disease
      are likely to share some common susceptibility genes, but these have not yet been
      identified. Evidence from various sources, including twin studies, segregation
      analyses, and case-control studies, support a heritable component to lung cancer
      risk in humans. As with many common diseases, susceptibility genes for lung
      cancer appear to be of low penetrance. Family studies of lung cancer
      susceptibility using linkage analysis and positional cloning have not been
      reported; however, a consortium is currently carrying out such studies, and
      results may soon be available. Association studies support lung cancer risk being
      partly determined by genes that control the metabolism of carcinogens found in
      tobacco smoke, with the heritable effects being most prominent in smokers with
      shorter smoking histories. Of these, the CYP1A1 and GSTM1 polymorphisms have been
      most consistently implicated. In the mouse, an oligonucleotide repeat
      polymorphism within an intron of the Ki-ras oncogene is the major lung cancer
      susceptibility locus; however this locus is not clearly involved in
      susceptibility to lung cancer in the human. Further understanding of the genetic
      basis of lung cancer susceptibility has many important implications, ranging from
      targeting prevention and screening efforts to the most highly susceptible
      population to developing novel chemopreventive therapies.

PMID- 16088540
TI  - Genetics of pulmonary fibrosis.
AB  - Identifying genetic determinants of pulmonary fibrosis is at an early stage of
      evolution. It is now well recognized that "pulmonary fibrosis" covers a broad
      range of lung diseases including most topically the idiopathic interstitial
      pneumonias that have been classified recently. Additionally, it is recognized
      that the diffuse lung diseases of children that may progress to fibrosis are
      quite different from those of adults. Defining clinical phenotype is an absolute
      prerequisite to precise identification of genetic determinants, and this is at
      least part of the reason why we understand relatively little of these genetic
      determinants to date. In children, a number of mutations have been identified,
      particularly with regard to surfactant protein. In adults, families with
      idiopathic pulmonary fibrosis are being collected but there are no genetic data
      on these at this point. In sporadic disease, associations have been reported in
      early phase genes with disease predisposition and also, importantly, with disease
      severity: future studies will inevitably incorporate issues of severity of
      disease in analyses.

PMID- 16088541
TI  - Genetics of sarcoidosis.
AB  - Sarcoidosis is a systemic disorder of granulomatous inflammation that primarily
      affects the lung and lymph system, although all organs can be involved. Two
      principal presentations of the disorder can be defined; an acute form, often with
      short duration and complete restitution, and a more insidious course with
      multiorgan involvement and a higher risk of progressive organ damage. Sarcoidosis
      affects mainly young adults. The etiology of sarcoidosis is unknown, and current
      concepts assume one or more environmental triggers that start in a host with an
      inherited susceptibility to a dysbalanced immune response. Candidate
      susceptibility genes include genes with a function in antigen recognition, T cell
      activation, T-helper 1/2 (TH1/TH2) cell balance, and granuloma formation. A few
      genetic linkage analyses and numerous association studies with a focus on the
      region of the major histocompatibility complex genes have been performed, which
      have so far yielded no breakthrough. They have, rather, verified the assumption
      of a complex and possibly heterogeneous character of the genetics of sarcoidosis.

PMID- 16088542
TI  - Host genetic factors in resistance and susceptibility to tuberculosis infection
      and disease.
AB  - The worldwide public health threat of tuberculosis and the search for novel
      strategies for preventing and treating disease have focused attention on the
      interaction between host and pathogen. Despite widespread presence of
      Mycobacterium tuberculosis, only a relatively small percentage of people exposed
      to the organism progress to clinical disease. Increasing evidence indicates that
      host genetic factors influence the outcome of exposure to M. tuberculosis. This
      evidence is presented here, along with strategies used to identify host genes
      responsible for resistance/susceptibility in MTB infection. Studies on host genes
      involved in response to infection by MTB and the relationships between infection
      and polymorphisms in immune response genes are reviewed. Research on how host
      genes can influence vaccine responses and the efficacy of drugs or other
      interventions as well as studies into the relationship of host genes to
      tuberculosis outcomes may lead to new strategies for prevention and control.

PMID- 16088545
TI  - Cor pulmonale: an overview.
AB  - Chronic cor pulmonale involves the enlargement of the right ventricle as a result
      of pulmonary hypertension due to pulmonary disorders involving the lung
      parenchyma, bellows function, or ventilatory drive. The right ventricular
      hypertrophy that occurs in chronic cor pulmonale is a direct result of chronic
      hypoxic pulmonary vasoconstriction and subsequent pulmonary artery hypertension,
      leading to increased right ventricular work and stress. We discuss methods by
      which hypoxic vasoconstriction and reduction in the pulmonary vascular bed lead
      to the development of pulmonary artery hypertension. This article reviews the
      interaction of the pulmonary vasculature and right ventricle in the non-diseased
      state as well as during disease exacerbations. Ventricular dependence and its
      contribution to the pathophysiology of right ventricular failure are also
      reviewed. In addition, we provide an overview of specific disease states that can
      result in the development of chronic cor pulmonale including chronic obstructive
      pulmonary disease (COPD), interstitial lung disease, sleep apnea, alveolar
      hypoventilation disorders, and primary pulmonary hypertension. We also review the
      current diagnostic studies used to evaluate and study cor pulmonale.

PMID- 16088546
TI  - Assessment of right ventricular morphology and function.
AB  - The assessment of right ventricular morphology and function is of clinical
      importance in patients with pulmonary disease. Until recently the evaluation of
      the right ventricle was difficult because of the unusual geometry of the right
      ventricle. This chapter discusses the various diagnostic modalities available for
      assessment of right ventricular morphology and function. Although
      echocardiography is widely used because of its common availability, nuclear
      magnetic resonance imaging and radionuclide angiocardiography should be
      considered the gold standards and are preferred when reliable and accurate
      measures of right ventricular function and morphology are needed.

PMID- 16088547
TI  - Pulmonary hypertension and cor pulmonale in COPD.
AB  - Pulmonary artery hypertension (PAH) is the primary cardiovascular complication
      encountered in chronic obstructive pulmonary disease (COPD). Cor pulmonale can
      range clinically from mild changes in right ventricular function to frank right
      heart failure. The prevalence of PAH increases as COPD worsens, and the
      development of PAH and cor pulmonale appears to affect survival of patients with
      COPD. Potential causes proposed to explain the development of PAH in COPD include
      gas exchange abnormalities, destruction of the pulmonary vascular bed,
      alterations in respiratory mechanics, changes in intrinsic pulmonary vessel tone,
      and increased blood viscosity. Standard clinical evaluation, including history,
      physical examination, spirometry, electrocardiography, and chest radiography, is
      generally inadequate in identifying right ventricular dysfunction. Noninvasive
      techniques, such as echocardiography, radionuclide ventriculography, and magnetic
      resonance imaging, have largely replaced invasive pulmonary artery
      catheterization in the initial assessment of cor pulmonale. The goals of therapy
      consist of attenuation of PAH, enhancement of right ventricular function,
      alleviation of clinical symptoms, and improvement in survival. The agents that
      have been most extensively evaluated for these purposes include oxygen,
      vasodilators, theophylline, and inotropic medications.

PMID- 16088548
TI  - Chronic thromboembolic pulmonary hypertension.
AB  - Over the past 4 decades, chronic thromboembolic pulmonary hypertension has
      evolved from an autopsy curiosity to a potentially correctable form of pulmonary
      hypertension. Approximately 2500 thromboendarterectomy procedures have now been
      performed worldwide with mortality rates reported by established programs
      experienced in the management of this disease process falling to a range of 4 to
      8%. Following a successful pulmonary thromboendarterectomy, substantial
      improvement, and at times normalization, can be achieved in right ventricular
      function, gas exchange, exercise capacity, and quality of life. Reperfusion lung
      injury and residual postoperative pulmonary hypertension remain the major causes
      of mortality in patients undergoing the procedure.

PMID- 16088549
TI  - Pulmonary hypertension in the collagen vascular diseases.
AB  - Pulmonary hypertension is increasingly recognized as a complication of the
      collagen vascular diseases. Both isolated and secondary forms of the disease may
      be appreciated. Pulmonary hypertension is observed with high prevalence in
      scleroderma and mixed connective tissue disease. It is less commonly seen in
      systemic lupus erythematosus, and is a rare clinical finding in rheumatoid
      arthritis. The diagnosis and treatment of pulmonary hypertension associated with
      the collagen vascular diseases mirror diagnosis and treatment for pulmonary
      hypertension of any etiology. Vasodilator therapy may play a particularly
      important role in patients with the isolated form of disease, which is most
      frequently associated with scleroderma.

PMID- 16088550
TI  - Cor pulmonale and sleep-disordered breathing in patients with restrictive lung
      disease and neuromuscular disorders.
AB  - Cor pulmonale frequently develops in patients with restrictive lung disease and
      neuromuscular disorders. Sleep disordered breathing, including nocturnal
      hypoventilation and obstructive apnea, has been associated with the development
      of cor pulmonale and may affect morbidity. The mechanisms responsible for sleep
      disordered breathing include defects in the control of breathing, respiratory
      muscle dysfunction, and abnormalities in chest wall and lung compliance. Symptoms
      of disturbed sleep may allow patients with sleep disordered breathing to be
      appropriately diagnosed and treated, often with nocturnal ventilation, before the
      development of right-sided heart failure.

PMID- 16088551
TI  - The right heart in congenital heart disease.
AB  - The clinical presentation of right ventricular (RV) dysfunction due to congenital
      heart disease (CHD) is similar to that of cor pulmonale. RV volume and pressure
      loads, and primary RV myocardial dysfunction are mechanisms by which CHD affects
      right heart function. RV volume load may arise from pre-tricuspid left to right
      shunts (e.g., atrial septal defect) or regurgitant lesions in the right heart
      (e.g., Ebstein's anomaly of the tricuspid valve and pulmonary insufficiency after
      repair of tetralogy of Fallot). RV pressure load may be caused by anatomic
      obstruction to RV outflow and by pulmonary arteriolar hypertension. The latter
      can result from Eisenmenger syndrome secondary to congenital and postoperative
      left to right shunts or from defects that cause pulmonary venous hypertension
      (e.g., pulmonary vein stenosis, cor triatriatum, or mitral stenosis). The RV
      myocardium may be affected by a primary cardiomyopathy or by congenital
      abnormalities of the coronary vessels. Finally, CHD may be associated with airway
      obstruction, scoliosis, or pulmonary emboli, which, in turn, may lead to the
      development of cor pulmonale. Congenital heart disease, therefore, must be
      included in the differential diagnosis of patients who present with right
      ventricular dysfunction.

PMID- 16088552
TI  - Cardiovascular abnormalities in sleep-disordered breathing.
AB  - The role of sleep-disordered breathing (SDB) in the development of persistent
      daytime pulmonary hypertension (PH) and cor pulmonale is controversial and has
      not been extensively studied. In this review we discuss the physiological changes
      that occur during SDB in the cardiovascular system, as well as review the most
      recent literature examining the relationship between SDB and PH/cor pulmonale.
      The literature suggests that much of the PH and right heart dysfunction seen in
      SDB is related to concurrent obesity and underlying lung disease, although it
      does appear that isolated SDB (in the form of obstructive sleep apnea) may be
      responsible for a small but significant degree of PH. The clinical consequences
      of this, however, remain unclear.

PMID- 16088553
TI  - Cor pulmonale in cystic fibrosis.
AB  - Cystic fibrosis is a common autosomal recessive disorder that is associated with
      a defective chloride transport channel in epithelial cells. The discovery of the
      cystic fibrosis gene in 1989 has led to a better understanding of the
      pathophysiology of the disease and the development of more effective therapeutic
      interventions. Chronic recurrent lung infections, pancreatic exocrine
      insufficiency, and elevated sweat chloride levels are hallmarks of the disease.
      Survival of patients with cystic fibrosis is steadily improving and most patients
      survive into adulthood. As lung disease progresses, secondary pulmonary
      hypertension and cor pulmonale are likely to develop. Pulmonary hypertension is
      correlated with the degree of hypoxemia and may be associated with increased
      mortality. The goal of therapy of cor pulmonale in cystic fibrosis is to correct
      hypoxemia and lower the elevated pulmonary artery pressures. This is best
      achieved by supplemental oxygen and aggressive treatment of the pulmonary disease
      with antibiotics and airway clearance techniques. It is also important to assess
      oxygenation during sleep and exercise. Bilateral lung transplantation is a
      treatment option for patients with end-stage lung disease, even in the presence
      of cor pulmonale.

PMID- 16088555
TI  - High-resolution computed tomography techniques in diffuse parenchymal lung
      disease and their application to clinical practice.
AB  - The remarkable ability of high-resolution computed tomography (HRCT) to provide
      sufficient detail of both normal and abnormal pulmonary anatomy requires high
      quality examinations with considerable attention paid to the technique. Despite
      the use of optimal scanning protocols, there are well-known limitations of
      sequential scanning that explain the recent interest in the use of multislice
      spiral CT for diagnosing lung diseases in routine clinical practice. A basic
      knowledge of the most recent developments in spiral CT technology appears a
      necessary prerequisite for those clinicians, pulmonologists, internists, or
      thoracic surgeons who are involved in the management of diffuse infiltrative lung
      diseases. This chapter reviews the various aspects of multislice spiral CT
      technology applied to routine clinical evaluation of diffuse infiltrative lung
      diseases.

PMID- 16088556
TI  - High-resolution computed tomography in the diagnosis of diffuse lung disease: a
      clinical perspective.
AB  - High-resolution computed tomography (HRCT) has a central role in the routine
      detection and diagnosis of individual diffuse lung diseases. The widespread use
      of HRCT has been stimulated by numerous published series, which have evaluated
      the accuracy of HRCT in cohorts of patients. However, these series have not
      simulated the integration of HRCT into clinical diagnosis, and this has led to
      difficulties in achieving the optimal diagnostic use of HRCT in routine practice.
      This article summarizes the problems facing the clinician in applying HRCT series
      to diagnosis in individual patients. The flaws in published series are discussed
      and the importance of integrating HRCT data with baseline clinical information
      and, in selected cases, histopathologic findings is highlighted.

PMID- 16088557
TI  - Insights from HRCT: how they affect the management of diffuse parenchymal lung
      disease.
AB  - High-resolution computed tomography (HRCT) has an established role in the
      detection and differential diagnosis of chronic diffuse infiltrative lung
      disease. Available data suggest that, in certain cases, HRCT may also be used to
      determine the presence or absence of, and extent of, abnormalities that are
      likely to reflect potentially reversible (acute or active) lung disease, as
      compared with irreversible (fibrotic) lung disease. In doing so, HRCT permits an
      assessment of disease prognosis. Furthermore, because HRCT can accurately
      identify subtle active lung disease, it may be used to monitor the success or
      failure of treatment. This article reviews the HRCT features associated with
      potentially reversible, as compared with irreversible, lung disease, and the
      accuracy with which these features can be used to predict disease activity and
      prognosis in chronic diffuse infiltrative lung disease and therefore assist
      management.

PMID- 16088558
TI  - Fibrotic idiopathic interstitial pneumonia: high-resolution computed tomography
      considerations.
AB  - The fibrotic idiopathic interstitial pneumonias comprise usual interstitial
      pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). The characteristic
      high-resolution computed tomography findings of UIP are reticular abnormality and
      honeycombing with basal and peripheral predominance. Honeycombing is the
      strongest predictor of UIP. The extent of fibrosis on computed tomography (CT) is
      an important prognostic indicator in idiopathic pulmonary fibrosis (IPF). When
      ground-glass attenuation is seen in IPF it commonly progresses to fibrosis and
      honeycombing. Imaging may help to detect complications of IPF, including
      accelerated progression, lung cancer, and secondary infection. Our understanding
      of the clinical and radiological features of NSIP is still evolving. The CT
      finding of extensive ground-glass abnormality and some reticular abnormality,
      with basal and peripheral predominance, is strongly suggestive of NSIP. However,
      the CT appearances of NSIP overlap with those of UIP, organizing pneumonia (OP),
      and desquamative interstitial pneumonia (DIP), and biopsy may be necessary to
      sort this out. Other idiopathic pneumonias that may be associated with CT
      evidence of lung fibrosis include DIP, OP, acute interstitial pneumonia, and
      lymphoid interstitial pneumonia.

PMID- 16088559
TI  - Smoking-related diffuse parenchymal lung disease: HRCT-pathologic correlation.
AB  - Response by the lung to inhaled cigarette smoke varies widely between individuals
      and ranges from subclinical respiratory bronchiolitis to end-stage Langerhans'
      cell histiocytosis. The variety of interstitial lung diseases associated with
      cigarette smoking is wider than generally appreciated, and these often coexist.
      An understanding of the pathological basis of smoking-related lung disease helps
      to explain the sometimes complex patterns encountered on high-resolution computed
      tomography (HRCT). The recent refinement of the classification of the idiopathic
      interstitial pneumonias and the longitudinal study of cigarette smokers with HRCT
      has furthered understanding of what should be regarded as an overlapping group of
      entities. In this article the individual interstitial diseases ascribable to
      cigarette smoking are discussed in terms of their pathology and corresponding
      HRCT signs. Emphasis is placed on the frequent coexistence of various forms of
      smoking-related interstitial lung disease.

PMID- 16088560
TI  - Computed tomographic scanning in sarcoidosis.
AB  - Sarcoidosis is a granulomatous disease of unknown etiology that involves the
      lungs or intrathoracic lymph nodes in more than 90% of patients. The clinical
      spectrum of sarcoidosis is protean, but pulmonary manifestations often dominate.
      Chest radiographs are abnormal in 90 to 95% of patients with sarcoidosis; the
      most characteristic feature is bilateral hilar lymphadenopathy (BHL), present in
      50 to 80% of patients. Pulmonary parenchymal infiltrates are present in 25 to 50%
      of patients. In this article, we review the radiographic features of sarcoidosis
      (both typical and atypical), and the impact of chest radiographic stage on long
      term prognosis. Computed tomographic (CT) scans are more sensitive than chest
      radiographs in delineating parenchymal, mediastinal, and hilar structures, and
      distinctive CT patterns may be virtually pathognomonic for sarcoidosis in some
      patients. Routine CT scan is not appropriate to diagnose or manage sarcoidosis,
      but CT may be invaluable in patients with atypical clinical or chest radiographic
      findings or specific complications of sarcoidosis (pulmonary or extrapulmonary),
      or to assess prognosis. High-resolution thin-section CT scans (HRCT) may be
      helpful in selected patients with stage II or III sarcoidosis to discriminate
      active inflammation from irreversible fibrosis. This article discusses the
      salient HRCT features of sarcoidosis, accuracy of CT in the differential
      diagnosis, and correlations of HRCT with disease extent and activity, pulmonary
      function, and lesion reversibility.

PMID- 16088561
TI  - The HRCT features of extrinsic allergic alveolitis.
AB  - Exposure to organic dusts can produce an immune-mediated inflammatory response in
      sensitized individuals. The pulmonary disease caused by this response has been
      called extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis. The
      clinical phases associated with this process have been termed acute, subacute,
      and chronic. There are corresponding imaging findings that are characteristic of
      each of these phases, although there is some overlap between the phases. The
      acute phase is characterized by confluent opacities that may mimic infection or
      edema. The subacute phase is characterized by centrilobular nodules, areas of
      ground-glass attenuation, a mosaic perfusion pattern, and air trapping on
      expiratory imaging. The chronic phase is characterized by subpleural irregular
      linear opacities with associated architectural distortion. Honeycombing may
      sometimes also be present. In the acute and subacute phases, the disease is
      predominantly in the lower lungs, whereas in chronic EAA the findings are
      predominant in the mid to upper lungs. Although the high-resolution computed
      tomography findings individually are nonspecific, the combination of the findings
      coupled with the distribution of the findings can often narrow the differential
      or allow a presumptive diagnosis of EAA to be made.

PMID- 16088562
TI  - Pulmonary vasculitis: CT features.
AB  - The pulmonary vasculitides are a heterogeneous group of inflammatory disorders
      that may be primarily localized to the pulmonary vasculature or be systemic in
      nature. The primary pulmonary vasculitides usually affect small vessels, whereas
      the systemic vasculitides can involve any size pulmonary vessels. For all types
      of vasculitis, there is a high degree of overlap within groups in regard to their
      appearance at computed tomography (CT). The most common CT findings are the
      result of either diffuse or focal pulmonary hemorrhage, are nonspecific, and
      include ground-glass opacity, consolidation, and small centrilobular nodules.
      Therefore, the CT findings must be considered in concert with the history,
      physical examination, and laboratory examination when a specific diagnosis is
      sought. This review will discuss the typical CT features of both the systemic and
      the primary pulmonary vasculitides, drawing a distinction where CT is helpful in
      differentiating among the various causes.

PMID- 16088563
TI  - Disorders of the small airways: high-resolution computed tomographic features.
AB  - Several infectious and noninfectious processes may affect predominantly or
      exclusively the small airways and result in reversible or irreversible
      abnormalities. Small-airway diseases can be considered as synonymous with
      bronchiolitis and can be classified into three main categories: (a) obliterative
      (constrictive) bronchiolitis, (b) cellular bronchiolitis, and (c) respiratory
      bronchiolitis. The introduction of high-resolution computed tomography (HRCT) has
      led to a considerable improvement in our ability to diagnose small-airway
      diseases. The characteristic HRCT findings of obliterative bronchiolitis consist
      of areas of decreased attenuation and vascularity with blood flow redistribution
      resulting in areas of increased lung attenuation and vascularity ("mosaic
      perfusion" pattern). In cellular bronchiolitis, the characteristic HRCT findings
      consist of centrilobular nodules and branching opacities ("tree-in-bud" pattern).
      Finally, bilateral areas of ground-glass attenuation and/or poorly defined
      centrilobular nodules are characteristic of respiratory bronchiolitis and
      respiratory bronchiolitis-associated interstitial lung disease (RB-ILD). This
      article reviews the clinical, pathological, and HRCT features of some of the most
      common small-airway diseases.

PMID- 16088564
TI  - Drug-induced lung disease: a pragmatic classification incorporating HRCT
      appearances.
AB  - Drug-induced lung disease frequently poses a diagnostic challenge. Knowledge of
      common radiological patterns of lung involvement and corresponding
      histopathologic diagnoses can facilitate management of individual patients. We
      outline a framework for understanding radiological and histologic patterns of
      drug-induced lung disease. Diffuse forms of drug-induced lung disease include
      processes that mimic acute respiratory distress syndrome (ARDS) and diffuse
      alveolar hemorrhage. These patterns of drug-induced lung disease are especially
      common in patients receiving cytotoxic chemotherapeutic agents. Chronic forms of
      drug-induced lung disease include many of the interstitial pneumonias seen more
      commonly in patients with idiopathic disease. Bronchiolitis obliterans organizing
      pneumonia and eosinophilic pneumonia are nonspecific patterns of drug-induced
      lung disease that are radiologically and histologically indistinguishable from
      their idiopathic counterparts. In some patients organizing pneumonia and
      eosinophilic pneumonia mimic the radiological appearance of neoplastic disease.

PMID- 16088566
TI  - Bronchiolar disorders: classification and diagnostic approach.
AB  - Bronchiolitis is a process in which inflammatory cells and mesenchymal tissue are
      both present, mainly centered in and around membranous and/or respiratory
      bronchioles, with sparing of a considerable portion of the other parenchymal
      structures. The distribution and amounts of the cellular and mesenchymal
      components vary from case to case, which accounts for the variety of
      histopathologic, radiographic, and clinical aspects of bronchiolitis. The
      clinical classification of bronchiolar diseases considers the causes or the
      clinical settings in which bronchiolitis develops: inhalation of toxic fumes,
      irritant gases or organic dusts, infectious and postinfectious bronchiolitis,
      collagen-vascular disease-associated bronchiolitis, posttransplant bronchiolitis,
      or rarer associations. A morphological classification based on histologic
      characteristics takes into account four main histologic patterns: cellular
      bronchiolitis, bronchiolitis with inflammatory/intraluminal polyps, constrictive
      or cicatritial bronchiolitis, peribronchiolar fibrosis, and bronchiolar
      metaplasia. High-resolution computed tomographic scanning (HRCT) is currently the
      best imaging technique for the evaluation of patients suspected of having
      bronchiolitis. HRCT findings in bronchiolar diseases with a good correlation with
      histopathologic changes are classified as follows: centrilobular tubular
      branching or nodular opacities; ground-glass attenuation or consolidation; mosaic
      perfusion; a mixed pattern. This article presents and briefly discusses the
      diagnostic approach to these diseases.

PMID- 16088567
TI  - Pathophysiology of the small airways.
AB  - This review describes, in some detail, the normal structure of the small airways,
      how this structure is achieved during the development of the bronchial tree from
      embryogenesis to adulthood, and how the structure determines the function of the
      airways at different ages and in disease. We then describe the structural
      abnormalities in small airways in chronic obstructive pulmonary disease (COPD)
      and their relationship with the disordered pulmonary function found in this
      disease, as an example of the mechanisms leading to airflow limitation in
      diseased airways. We address the pathology of small airways in different stages
      of COPD, summarizing the structural abnormalities associated with the progressive
      deterioration of pulmonary function from smokers with normal lung function to
      smokers with severe COPD. The importance of the elastic recoil in the normal and
      abnormal function of the airways is also highlighted.

PMID- 16088568
TI  - Imaging of the small airways.
AB  - Small airways disease (SAD) is defined as a pathologic condition in which the
      small conducting airways are affected either primarily or as part of other
      pulmonary changes. Diagnosis is often difficult because the many histopathologic
      subtypes that have been described often lack obvious clinical or imaging
      correlates and because widespread involvement is needed before clinical symptoms
      and abnormalities on pulmonary function testing occur. High-resolution computed
      tomography (HRCT) can be helpful to detect, characterize, and quantify small
      airways involvement. These airways may become visible directly when inflammation
      of the bronchiolar wall and accompanying exudates develop. Obstruction of the
      small airways may be detected indirectly by HRCT when it causes regional
      underventilation resulting in reduced perfusion. This article discusses the
      direct and indirect HRCT signs of small airways involvement and, based on the
      fundamental differences between these signs, gives a short review of the HRCT
      features of the most important diseases that can affect the small airways.

PMID- 16088569
TI  - Histopathology of bronchiolar disorders.
AB  - Bronchiolar pathologic lesions result from the interplay between inflammatory and
      mesenchymal cells following injury to bronchioles. Offending agents include
      viruses, bacteria, fungi, cigarette smoke, toxic inhalants, inorganic dusts,
      allergens, and systemic or localized autoimmune or inflammatory processes.
      Bronchiolar pathologic lesions also arise in the context of allograft
      transplantation and pathology of the large airways and in the setting of an
      idiopathic disorder. Given the great variety of sources of injury and diversity
      of clinical, radiological, and functional patterns that result, it is no surprise
      that most morphological abnormalities of the bronchioles are not specific. They
      thus represent a diagnostic challenge to the surgical pathologist, and the
      necessity of a multidisciplinary (clinical/radiological/pathologic) approach
      cannot be overemphasized. After a survey of the normal histology of bronchioles,
      we present a pragmatic classification that reflects the spectrum of bronchiolar
      pathology, illustrating the intimate interdependence of clinical, radiological,
      and pathologic findings in assessing the significance of bronchiolar lesions.
      This classification is intended to be applicable to surgical pathology material
      that can be correlated with clinical disease syndromes. It includes asthma
      associated bronchiolar changes, chronic bronchitis/emphysema-associated
      bronchiolar changes, cellular bronchiolitis, respiratory bronchiolitis,
      bronchiolitis obliterans with intraluminal polyps/ BOOP, constrictive
      bronchiolitis, mineral dust small airway disease, peribronchiolar fibrosis and
      bronchiolar metaplasia, and bronchiolocentric nodules.

PMID- 16088570
TI  - Bronchiolitis obliterans syndrome complicating lung or heart-lung
      transplantation.
AB  - Lung transplantation is a therapeutic option for patients with end stage lung
      diseases, but long-term survival remains poor, primarily due to chronic allograft
      rejection. Bronchiolitis obliterans (BO), a fibrotic process resulting in
      progressive narrowing of bronchiolar lumens and airflow obstruction, is a
      manifestation of chronic allograft rejection. The term obliterative bronchiolitis
      ( OB) is synonymous. Once bronchiolitis obliterans syndrome (BOS) develops,
      progressive decline in pulmonary function is typical; most patients die of
      respiratory failure within 5 years of onset. The diagnosis of BOS is usually made
      by clinical, physiological, and radiographic parameters. The dominant risk factor
      for BOS is acute allograft rejection, but additional factors play contributory
      roles [e.g., infections; human leukocyte antigen (HLA) mismatching; and injury to
      the allograft or airways]. The pathogenesis of BOS is complex and involves myriad
      cell types (both immune and nonimmune) and release of diverse cytokines and
      chemokines. Unfortunately, current therapies for BOS are of unproven value. A
      greater understanding of the pathogenic mechanisms operative in BOS are critical
      to developing novel strategies to treat and prevent this devastating
      complication.

PMID- 16088571
TI  - Obliterative bronchiolitis complicating bone marrow transplantation.
AB  - Respiratory complications of bone marrow transplantation comprise the majority of
      its morbidity and mortality. Obstructive airways disease is the most common
      noninfectious respiratory complication, usually indicative of obliterative
      bronchiolitis (OB), which occurs in 9% of allogeneic marrow transplant patients.
      OB is rarely seen after autologous transplant because chronic graft versus host
      disease (GVH), the most commonly identified risk factor, does not occur in this
      setting. Alloreactive immunity is likely the cause, with donor type 2 T-helper
      (TH2) lymphocytes the primary mediators. OB presents at 6 to 12 months post
      transplant with cough and dyspnea. Results of investigations include relatively
      normal or hyperinflated chest radiographs; thickened, dilated airways; and mosaic
      attenuation on high-resolution computed tomography (HRCT), and fixed airflow
      obstruction, hyperinflation, and gas trapping on physiological testing.
      Bronchoscopy and lavage are performed primarily to exclude infections.
      Transbronchial biopsy is often nondiagnostic, but because the clinical diagnosis
      is generally sufficient, surgical biopsy is not usually recommended. Histology
      reveals lymphocytic bronchiolitis, concentric bronchiolar fibrosis, and
      bronchiolar obliteration. Corticosteroids remain the mainstay of treatment, which
      is usually required for 3 to 9 months. Response is generally poor, with mortality
      between 40 and 100%, and lung function infrequently improves. Stabilization with
      permanent respiratory impairment is common. Early detection and prompt
      immunosuppression may improve outcomes.

PMID- 16088572
TI  - Bronchiolar complications of connective tissue diseases.
AB  - Inflammatory and fibrotic processes can involve the small airways (i.e.,
      respiratory and terminal bronchioles) in several connective tissue disorders
      (CTDs). Obliterative (constrictive) bronchiolitis (OB) as well cryptogenic
      organizing pneumonia (COP), previously termed bronchiolitis obliterans with
      organizing pneumonia (BOOP), are well-recognized, albeit rare, complications of
      rheumatoid arthritis and other CTDs. Bronchiectasis has also been described in
      patients with CTDs. Among the various pathologic conditions, clinical,
      radiographic, and histologic features and prognosis differ markedly. Clinical
      features are often nonspecific, and sometimes patients may be asymptomatic.
      Diagnosing these disorders may be difficult. High-resolution computed tomography
      (HRCT) is useful in detecting bronchiolar pathology, even when symptoms are
      minimal or absent. Surgical (open or thoracoscopic) lung biopsies can
      substantiate the diagnosis, but in some cases, the diagnosis can be affirmed less
      aggressively by appropriate imaging studies (e.g., HRCT) and transbronchial lung
      biopsies. Corticosteroids are highly efficacious for COP, but therapeutic options
      for OB are disappointing. Prophylactic antibiotics and good pulmonary hygiene
      remain the mainstay of therapy for patients with bronchiectasis.

PMID- 16088573
TI  - Miscellaneous causes of bronchiolitis: inhalational, infectious, drug-induced,
      and idiopathic.
AB  - Bronchiolitis is increasingly recognized as an important clinical syndrome that
      encompasses the broad spectrum of histopathologic processes which show some
      degree of inflammation, narrowing, or obliteration of the small conducting
      airways. It has an extremely variable clinical course, etiology, and histologic
      appearance. Understanding of this entity has been limited because until recently
      only case reports described this lesion in several diverse clinical settings. In
      addition, there has been considerable confusion as a result of the different
      terminologies applied to the many syndromes. This article reviews the clinical,
      radiographic, and histopathologic findings of the bronchiolar syndromes that are
      secondary to inhalation of chemicals or organic dust, that are secondary to
      infection, that are drug-induced, and that have no known etiology (idiopathic).

PMID- 16088574
TI  - Bronchiolitis caused by occupational and ambient atmospheric particles.
AB  - Occupationally encountered mineral dusts such as asbestos, silica, silicates
      (talc, mica), and metals can produce a distinctive pattern of fibrosis and
      distortion of the small airways, particularly the distal membranous bronchioles
      (MB) and the respiratory bronchioles (RB). Recent reports show that the same
      types of changes, accompanied by considerable muscle hyperplasia, are found in
      individuals living in regions with high levels of particulate air pollutants
      (PM). Models and actual measurements suggest that these changes occur because the
      small airways are sites of high particle deposition, and inhaled and deposited
      particulates, including PM, enter the airway walls. Studies from our laboratory
      using a tracheal explant model have shown that, for many types of particles,
      entry into the airway wall causes expression of mediators that lead to airway
      wall fibrosis and airway wall smooth muscle hyperplasia, probably through oxidant
      mechanisms. These reactions are intrinsic properties of the particles and do not
      require exogenous inflammatory cells. There is considerable evidence that
      individuals with occupational exposure to a wide variety of mineral dusts, as
      well as individuals with chronic exposure to high levels of PM, develop chronic
      airflow obstruction. The type of small airway remodeling seen in particle-induced
      bronchiolitis appears to be one cause of chronic airflow obstruction in this
      setting.

PMID- 16088575
TI  - Respiratory bronchiolitis-associated interstitial lung disease.
AB  - Respiratory bronchiolitis-associated interstitial lung disease (RBILD) can be
      viewed as an exaggerated respiratory bronchiolitic response to cigarette smoke.
      The histologic, high-resolution computed tomographic (HRCT) and bronchoalveolar
      lavage (BAL) features of RBILD overlap substantially with those of respiratory
      bronchiolitis, with the diagnosis of RBILD being based upon the severity of
      disease, as judged by symptoms, clinical signs, the severity of lung function
      impairment, and the extent of abnormalities on HRCT. Typical histologic
      appearances consist of an accumulation of pigmented macrophages within
      respiratory bronchioles, associated with peribronchial chronic inflammatory cell
      infiltration and, variably, peribronchial fibrotic alveolar septal thickening.
      Characteristic HRCT findings include poorly defined centrilobular micronodules,
      patchy limited ground-glass attenuation, bronchial wall thickening, and areas of
      regional hypoattenuation. The ventilatory defect is often mixed but is usually
      predominantly restrictive. The diagnosis of RBILD is often made on clinical and
      HRCT criteria, with BAL findings providing useful diagnostic support, but a
      thoracoscopic biopsy continues to be required when other features are atypical.
      RBILD may regress with discontinuation of smoking but often persists with no
      functional improvement despite smoking cessation and treatment. Nonetheless, the
      course tends to be benign, without inexorable deterioration. This article
      outlines the rationale for viewing RBILD and desquamative interstitial pneumonia
      as separate entities, rather than two ends of the same disease spectrum (based
      upon overlapping histologic and HRCT features).

PMID- 16088576
TI  - Organizing pneumonia: cryptogenic and disease associated.
AB  - Organizing pneumonia is defined by the presence of buds of granulation tissue
      (fibroblastic cells and connective matrix) within the alveolar lumen, usually
      associated with proliferative bronchiolitis obliterans. It may result from
      several causes, but cryptogenic organizing pneumonia is a distinct
      clinicopathologic entity with characteristic clinical and imaging features.
      Typical COP is thus easily recognized by the clinician, and the diagnosis is made
      by the finding of organizing pneumonia on lung biopsy specimen. The response to
      corticosteroids is rapid and complete usually without sequelae, but relapses
      occur frequently and prolonged corticosteroid treatment is often necessary.

PMID- 16088577
TI  - Diffuse panbronchiolitis.
AB  - Diffuse panbronchiolitis (DPB) was first distinguished from chronic obstructive
      pulmonary diseases in the early 1960s and recorded as a new clinicopathologic
      entity. This disease affects East Asians for the major part, and is characterized
      by chronic sinobronchial infection together with diffuse bilateral micronodular
      pulmonary lesions consisting of inflammatory cells. The prognosis at an advanced
      stage would often be bleak, where superinfection with Pseudomonas aeruginosa had
      occurred. Beginning with an initial success of erythromycin therapy, considerable
      improvement has been achieved in the prognosis of this disease. Simple
      bactericidal activity of macrolides is not a determinant factor for the clinical
      effect. An in-depth study, together with its pathogenesis, has been performed to
      clarify the underlying mechanism. Inhibitions of excessive mucus and water
      secretion from airway epithelium, neutrophil accumulation in the large airway,
      lymphocyte and macrophage accumulation around the small airway, and modulation of
      bacterial virulence have so far been proposed as possible mechanisms.

PMID- 16088578
TI  - Overview of cystic fibrosis and non-CF bronchiectasis.

PMID- 16088579
TI  - Genetics of cystic fibrosis.
AB  - Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance
      regulator (CFTR) gene, which encodes a protein expressed in the apical membrane
      of exocrine epithelial cells. CFTR functions principally as a cyclic adenosine
      monophosphate (cAMP)-induced chloride channel and appears capable of regulating
      other ion channels. Mutations affect CFTR through a variety of molecular
      mechanisms, which can produce little or no functional gene product at the apical
      membrane. More than 1000 different disease-causing mutations within the CFTR gene
      have been described. The potential of a mutation to contribute to the phenotype
      depends on its type, localization in the gene, and the molecular mechanism as
      well as on interactions with secondary modifying factors. Genetic testing can
      confirm a clinical diagnosis of CF and can be used for infants with meconium
      ileus, for carrier detection in individuals with positive family history and
      partners of proven CF carriers, and for prenatal diagnostic testing if both
      parents are carriers. Studies of clinical phenotype in correlation with CFTR
      genotype have revealed a very complex relationship demonstrating that some
      phenotypic features are closely determined by the underlying mutations, whereas
      others are modulated by modifier genes, epigenetic mechanisms, and environment.

PMID- 16088580
TI  - Non-genetic influences on cystic fibrosis lung disease: the role of
      sociodemographic characteristics, environmental exposures, and healthcare
      interventions.
AB  - Patients with cystic fibrosis (CF) exhibit significant variability in the course
      and severity of the disease, and this variability is best interpreted in the
      context of an interaction between genetic and nongenetic determinants. While a
      small number of patients with "mild" mutations in the CF transmembrane
      conductance regulator gene clearly have less severe disease, for the general
      population of patients with CF the strongest predictor of severity of clinical
      course appears to be socioeconomic status (SES). Low SES probably exerts an
      influence via the convergence of detrimental environmental influences on outcome
      such as environmental tobacco smoke, poor nutrition, and stress. Other important
      predictors that appear to be independent of SES include gender and acquisition of
      airway pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia complex.
      Finally, effective provision of medical interventions is an important determinant
      of outcome, and this is affected primarily by patient adherence (which bears a
      poorly defined relationship to SES), and attendance at a CF care center that
      utilizes a system of care that allows optimal delivery of evidence-based
      interventions.

PMID- 16088581
TI  - Primary ciliary dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by
      impaired ciliary function that leads to an array of clinical manifestations
      including chronic bronchitis, chronic sinusitis, chronic otitis media, situs
      inversus (in approximately 50% of cases), and infertility. The underlying genetic
      and molecular defects have not been defined. Molecular genetic studies have
      demonstrated multiple gene loci. In a few families, defects in genes encoding
      ciliary dynein proteins have been identified. PCD is an interesting disease to
      compare with cystic fibrosis (CF) because both are airway diseases associated
      with impaired mucociliary clearance and with chronic infection of the airways
      leading to bronchiectasis as well as chronic infection of the sinuses that may be
      associated with nasal polyposis. The progression of the lower airway disease
      appears less rapid in PCD. Unlike CF, PCD is commonly associated with chronic
      otitis media, respiratory problems during the neonatal period, and situs
      inversus, suggesting that ciliary function is also important for clearing
      fluid/bacteria from the middle ear, for clearing fluid from the fetal lung during
      the transition to an air-filled neonatal lung, and for directing laterality of
      organs during embryonic development. The management for PCD lung disease is
      similar to that for CF and other diseases with chronic bronchitis leading to
      bronchiectasis.

PMID- 16088582
TI  - The role of biofilms in airway disease.
AB  - Biofilms are defined as collections of microorganisms attached to a surface and
      embedded in a matrix. This attached state is the primary mode of microbial growth
      in the environment and within the body. However, biofilms represent a significant
      clinical concern because they are recalcitrant to antimicrobial agents. This is
      particularly troublesome in the respiratory tract where biofilms clearly
      complicate traditional therapies. This review focuses on the biology,
      development, and antimicrobial resistance properties of biofilms formed by three
      significant respiratory tract pathogens; Pseudomonas aeruginosa, Staphylococcus
      aureus, and Haemophilus influenzae. Recent research has begun to shed light on
      the molecular events governing biofilm formation and antimicrobial resistance
      mechanisms with these organisms. A deeper understanding of these concepts will be
      necessary for the development of rational strategies to control biofilms in the
      future.

PMID- 16088583
TI  - Pseudomonas aeruginosa: role in the pathogenesis of the CF lung lesion.
AB  - Lung disease is the leading cause of morbidity and mortality in individuals with
      cystic fibrosis (CF), with P. aeruginosa the main pulmonary infectious agent.
      Although CF patients can become infected with other microorganisms (such as
      Burkholderia cepacia complex, Staphylococcus aureus, Haemophilus influenzae, and
      atypical mycobacteria), P. aeruginosa predominates, eventually infecting
      approximately 80% of patients. Once established, P. aeruginosa infection usually
      persists until death. The interaction between the CF host and this opportunistic
      pathogen is unique and most likely directly contributes to the classical end
      stage pathology of CF lung disease. However, the extent to which this constitutes
      success by the pathogen or failure by the host, or both, is yet to be determined.
      Many important questions remain regarding host susceptibility, the role of both
      innate and adaptive immune defenses, bacterial infectivity and transmission, and
      pathogen virulence factors. Here, we discuss some recent advances toward
      understanding this complex interaction between host and pathogen and how the
      interplay influences the CF lung lesion.

PMID- 16088584
TI  - Burkholderia and emerging pathogens in cystic fibrosis.
AB  - Persons with cystic fibrosis (CF) are susceptible to respiratory tract infection
      with a variety of bacterial species. Among these are several species in the genus
      Burkholderia (including members of the B. cepacia complex, B. gladioli, and B.
      pseudomallei), Stenotrophomonas maltophilia, Achromobacter ( Alcaligenes)
      xylosoxidans, certain Ralstonia species, and species within the new genus
      Pandoraea. Enterobacteriaceae and several other rather unusual or novel species
      also can be found. Many of these species are closely related phylogenetically and
      have similar phenotypes, presenting a challenge to accurate laboratory
      identification. Although their role in contributing to pulmonary disease in CF is
      not clear, the incidence of infection by some of these species appears to be
      increasing. The broad-spectrum antimicrobial resistance typically exhibited by
      these species severely limits treatment options. Newly developed genotypic
      methods of identification will enable studies to better assess the epidemiology
      and natural history of these emerging pathogens in CF.

PMID- 16088585
TI  - Nontuberculous mycobacteria in cystic fibrosis.
AB  - Nontuberculous mycobacteria (NTM) are widely distributed in our modern
      environment. Therefore, it is not surprising that these organisms are commonly
      present in sputum from cystic fibrosis (CF) patients. In the setting of CF lung
      disease, the significance of NTM in respiratory secretions is a major diagnostic
      challenge. The usual signs, symptoms, and radiographic features of NTM disease
      are also characteristic of CF lung disease; thus it is difficult to determine
      whether the NTM are a saprophytic contaminant or an active pathogen. Although
      many CF patients appear to tolerate the presence of the NTM without clear
      evidence of disease, some suffer accelerated progression of lung disease that
      cannot be solely attributed to CF and appear to benefit from antimycobacterial
      treatment. Standard CF care should be reemphasized in patients with NTM
      infection, especially aggressive bronchial hygiene. Specific guidelines for
      antimycobacterial therapy in CF patients have not been determined, and potential
      complications of treatment are significant. Hence, patients offered
      antimycobacterial treatment must be selected carefully. An initial approach to
      treatment of CF patients is based on guidelines developed for the general
      population.

PMID- 16088586
TI  - Patient cohorting and infection control.
AB  - Patients with cystic fibrosis (CF) have an abnormal propensity for recurrent and
      chronic infections of the lower respiratory tract (LRT), and the most common
      cause of a shortened lifespan is chronic infection with Pseudomonas aeruginosa. A
      few other gram-negative organisms, primarily Burkholderia cepacia complex have,
      however, emerged as serious pathogens capable of establishing chronic LRT
      infection. Details of these and other CF pathogens can be found in the article by
      Dr. John LiPuma, Burkholderia and Emerging Pathogens in Cystic Fibrosis, in this
      issue. Chronically infected patients constitute a major microbial reservoir from
      which noninfected patients can be infected with both P. aeruginosa and B. cepacia
      complex by direct patient-to-patient transmission, and possibly also by exposure
      to contaminated environments. Other more rare pathogens such as Stenotrophomonas
      maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM)
      appear less capable of causing patient-to-patient transmission. Both the physical
      proximity and the duration of exposure of noninfected patients to patients
      chronically infected with P. aeruginosa and B. cepacia complex are important
      determinants of the risk of cross-infection. Cohorting of patients according to
      presence or absence of specific pathogens coupled with conventional hygienic
      precautions can, however, lead to a decrease in incidence and prevalence of
      chronic infections with these two species, wherefore patient cohorting is now an
      integral component of infection control in patients with CF.

PMID- 16088587
TI  - Aerosolized antibiotics in cystic fibrosis.
AB  - Inhaled antibiotics offer an attractive alternative to systemic administration in
      cystic fibrosis (CF) for several reasons. Antibiotics can be administered
      directly to the site of infection with little systemic absorption, thereby
      minimizing toxicity. Aerosolization will permit chronic administration of
      antipseudomonal antibiotics while avoiding the risks and inconvenience of
      intravenous access. Modern aerosolized drug delivery systems enable endobronchial
      delivery of very high antibiotic concentrations, resulting in clinical
      improvement even in patients with bacterial organisms that traditionally would
      have been considered resistant. This article summarizes basic concepts of aerosol
      drug administration and reviews available data on the administration of a variety
      of drug classes for both suppressive therapy and acute exacerbations of cystic
      fibrosis, including toxicity and safety data. The aminoglycosides have been by
      far the most extensively studied class of antibiotics, culminating in U.S. Food
      and Drug Administration (FDA) approval of a specifically formulated tobramycin
      solution for inhalation. The available data on the development of antibiotic
      resistance and emergence of other organisms with long-term use of this agent are
      reviewed. Finally, a brief guideline for initiating and monitoring patients on
      antibiotic aerosols is provided for the clinician caring for CF patients.

PMID- 16088588
TI  - Airway clearance techniques.
AB  - The airways of the patient with cystic fibrosis (CF) are chronically infected.
      There is excess mucus within the airways and, because of the chronic infection,
      the mucus also contains bacteria and inflammatory cells. Mucociliary clearance is
      impaired in patients with CF, and patients become dependent upon cough and other
      techniques to clear their airways of the thick sputum. This review discusses the
      various techniques and medications that have been demonstrated to be effective at
      assisting the clearance of the excess secretions in the CF airways. No single
      method has been proven to be better than the others, and not all patients will
      benefit, or use, the same techniques. Therefore, the methods of airway clearance
      must be tailored for each patient to assure effective therapy.

PMID- 16088589
TI  - Macrolides as biological response modifiers in cystic fibrosis and
      bronchiectasis.
AB  - For 50 years, macrolide antibiotics have been used to treat community acquired
      pneumonia and atypical infections such as Chlamydia pneumonia and Mycoplasma. In
      the late 1960s it was noted that when the 14-member ring macrolide antibiotic
      troleandomycin was given to asthma patients who required large doses of systemic
      corticosteroids, they could often reduce their steroid dose or even stop steroids
      completely without exacerbation of their asthma. Because of this experience,
      Prof. S. Kodoh and colleagues first used erythromycin as an immunomodulatory
      agent to treat diffuse panbronchiolitis (DPB). DPB is a cystic fibrosis (CF)-like
      condition seen predominantly in young, nonsmoking adults in Japan and Korea. The
      introduction of erythromycin profoundly improved survival, and in many of these
      very ill patients the illness disappeared. Since then, research has focused
      attention on many non-antibacterial, disease modifying effects of this class of
      compounds. These include downregulation of proinflammatory cytokines via an
      effect on nuclear transcription factors, reduction in adhesion molecule
      expression, suppression of inducible nitric oxide synthase (iNOS), reduced
      neutrophil chemotaxis and degranulation, inhibition of neutrophil elastase,
      cytoprotection against bioactive phospholipids, improvement in the rheological
      properties of mucus, reduction in bronchial hyperreactivity, and, perhaps,
      modulation of neutrophil death by apoptosis pathways, and in the end, airway
      remodeling. Additionally, they have unconventional effects on microorganisms,
      including inhibiting Pseudomonas aeruginosa twitching motility and thus biofilm
      formation. There are small case series and three large randomized controlled
      trials that have established unequivocal evidence of benefit in CF. There is less
      evidence for an immunomodulatory effect in bronchiectasis. Future work is likely
      to focus on the development of macrolides with disease-specific modes of action.

PMID- 16088591
TI  - Management of emergencies in critical care.

PMID- 16088590
TI  - The status of gene therapy for cystic fibrosis.
AB  - Cystic fibrosis (CF) has been a primary focus for gene therapy of lung diseases
      because the genetic cause is known and the airway epithelium is accessible for
      direct deoxyribonucleic acid (DNA) delivery. Soon after the mutated gene was
      identified in 1989, investigators demonstrated that transfer of a normal copy of
      the CF gene corrected ion transport abnormalities, thus validating the potential
      for use of gene therapy for this autosomal recessive disease. However, subsequent
      studies in a variety of in vitro and animal models, and more limited human
      studies, have revealed several obstacles to gene therapy for CF: (1) The
      incomplete understanding of CF lung disease pathogenesis, particularly the
      relative importance of ion transport and other cellular abnormalities (including
      glycoconjugate processing, pH regulation of intracellular organelles, and
      membrane trafficking), and of surface epithelial versus submucosal gland CF
      transmembrane regulator (CFTR) expression, generates uncertainty as to the
      necessary target cells for gene transfer and the optimum end point(s) for short
      term human studies. (2) The airway epithelium has protective barriers against
      viral infection that impair gene transfer with several vectors, including
      recombinant viruses and DNA conjugates. Improvement in DNA transfer technology
      will be necessary for successful gene therapy. (3) Immune responses to
      recombinant viruses and inflammatory effects of bacterial DNA are only partially
      understood and appear to limit efficacy, particularly with repeated
      administration. Identification of these obstacles is prerequisite for progress,
      and recent studies with novel DNA delivery methods appear promising.

PMID- 16088592
TI  - Troubleshooting and managing the difficult airway.
AB  - Difficult airways are an inevitable part of the delivery of emergency and
      critical care. Failure to achieve or restore a patent airway can lead, in a
      matter of minutes, to hypoxic neurological injury and death in critically ill
      patients. As with many conditions, the keys to success in a moment of crisis are
      forethought and preparation. Clinicians should be able to recognize risk factors
      for difficult airways and plan accordingly. In the face of failed direct
      laryngoscopy, a variety of rescue techniques are available. Familiarity with many
      strategies, and practiced dexterity with one or two, should be part of every
      intensivist's plan for the management of this life-threatening problem.

PMID- 16088593
TI  - Interfacility transports.
AB  - Financial pressures exerted by managed care organizations toward hospitals to
      improve efficiencies and to lower total healthcare costs continue to force
      physicians and administrators to reevaluate operations and practices. This
      shifting of risk exposure from insurers to providers has resulted in many
      mergers, acquisitions, and affiliations, so as to form integrated health systems
      that reduce repetition and duplication of services. Therefore, as these
      integrated systems develop, along with the emergence of tertiary care, regional
      referral, and specialty hospitals, the need for patient transfers between such
      facilities will expand. The decision to move patients between facilities is a
      multicomponent process comprising health, safety, financial, and legal concerns.
      Interfacility transportation of patients has been performed over the past 20 to
      30 years. Whereas ground transport services were prominent in the 1970s, air
      medical programs using helicopters and fixed-wing aircraft have recently become
      widespread. Both hospital-based and private agencies have continued to develop
      programs for efficiently and expeditiously transporting critically ill or injured
      patients, many requiring complex life-support devices. The Practice Management
      Committee of the American College of Emergency Physicians recently updated the
      1990 policy statement on interfacility transfers, and two position statements are
      available from the National Association of EMS Physicians on criteria for air
      medical transport and medical direction for interfacility transport services.
      This review provides an overview of transportation systems and services available
      and assists physicians in understanding the various modes and characteristics of
      systems available. Personnel configurations and capabilities, physiological
      limitations, inherent requirements for equipment and patient preparation, and
      legal issues involved with transferring patients are also outlined.

PMID- 16088594
TI  - Calcium and beta receptor antagonist overdose: a review and update of
      pharmacological principles and management.
AB  - Calcium channel and beta-adrenergic receptor antagonists are common
      pharmaceutical agents with multiple overlapping clinical indications. When used
      appropriately, these agents are safe and efficacious. In overdose, however, these
      agents have the potential for serious morbidity. Calcium channel blockers and
      beta blockers share similar physiological effects on the cardiovascular system,
      such as hypotension and bradycardia, in overdose and occasionally at therapeutic
      doses. The initial management for symptomatic overdose of both drug classes
      consists of supportive care measures. Other therapies including administration of
      glucagon, calcium, catecholamines, phosphodiesterase inhibitors and insulin have
      been used with varying degrees of success. In addition, intra-aortic balloon pump
      and extracorporeal membrane oxygenation techniques have been successfully
      utilized in refractory cases. This article reviews beta blocker and calcium
      channel blocker pharmacological principles and updates current management
      strategies.

PMID- 16088595
TI  - Amphetamine toxicity.
AB  - Amphetamine abuse is widespread and associated with significant health risk. The
      most commonly encountered amphetamines are methamphetamine, 3,4
      methylenedioxymethamphetamine (MDMA, Ecstasy), and the ephedra alkaloids.
      Although each of these harbors unique toxicity, they similarly impact the
      cardiovascular and neurological systems in overdose. Other serious complications
      associated with amphetamine abuse include severe hyperpyrexia and hyponatremia.
      Secondary conditions such as rhabdomyolysis, disseminated intravascular
      coagulation (DIC), gastrointestinal (GI) bleeding, hepatic necrosis, and renal
      failure are common, especially in those with hyperthermia. Chronic abuse poses
      risk of vasculitis, neuropsychiatric abnormalities, and cardiomyopathy. In
      addition, there is a growing body of evidence that even recreational abuse of
      methamphetamine and MDMA may produce long-lasting damage to dopaminergic and
      serotonergic neurons. Management principles include adequate sedation, aggressive
      cooling, and the use of titratable agents in the management of cardiovascular
      abnormalities.

PMID- 16088596
TI  - Traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a serious health issue in the United States,
      killing 100,000 people a year and serving as a source of long-term disability for
      many more. It is the leading cause of death in patients under the age of 45
      years. Successful management of TBI requires first an appreciation that a
      significant part of the neuronal injury incurred following trauma is secondary
      and is a result of disordered homeostatic mechanisms rather than the mechanical
      energy of the initial insult. Key skills in the care of brain-injured patients
      include adequately gauging the severity of injury, recognizing the primacy of
      sufficient blood flow and oxygen delivery to the injured brain, and being able to
      detect and correct when possible local and global physiological abnormalities
      that frequently put the injured brain at ongoing risk within the intensive care
      unit. This article discusses these issues, including invasive hemodynamic and
      intracranial monitoring, useful methods for reducing intracranial pressure, and
      management of complications arising from acute head injury.

PMID- 16088597
TI  - Submersion injuries in children and adults.
AB  - Drowning is defined as death by suffocation after submersion in a liquid medium.
      Near drowning is a term used when a patient recovers, at least temporarily, from
      the drowning episode. Most authors include loss of consciousness while submerged
      to complete the criteria of near drowning. In its Guidelines 2000 Conference, the
      American Heart Association urged that the term near drowning no longer be used
      and that it be replaced by the term submersion injury.

PMID- 16088598
TI  - Hypothermia.
AB  - Accidental hypothermia is defined as an unintentional decline in the core
      temperature below 35 degrees C. The population of patients at risk is very
      heterogeneous. Common thermal stressors include both primary exposures and
      secondary contributory diseases or injuries. As the core temperature
      progressively declines, the compensatory metabolic, adrenergic, and
      cardiovascular responses that attempt to maintain thermal homeostasis fail. At
      this juncture, therapeutic intervention must occur. An understanding of the
      pathophysiological variables impacting rewarming is critical. For example, the
      effects of cold on the coagulation system impact both the approach to
      cardiovascular resuscitation and the choice of rewarming technique. There are no
      randomized controlled trials that definitively establish the ideal rewarming
      strategy for each unique presentation. The resuscitative goal is to match the
      clinical presentation with the threshold temperatures at which various rewarming
      modalities and pharmacological interventions should occur. Identification of the
      indications for both noninvasive and invasive active rewarming techniques in
      patients requiring critical care is key. Poikilothermia, failure to rewarm,
      endocrinologic insufficiency, cardiovascular instability, traumatic or
      toxicological induced peripheral vasodilation, or the presence of major
      predisposing factors mandates active rewarming. The simultaneous or sequential
      use of the various rewarming techniques permits a versatile approach to therapy.
      Outcome remains problematic to predict because there may never be a validated
      prognostic neurological scale. The history, physical examination, and,
      ironically, the vital signs are routinely misleading. A tachycardia that is not
      proportionate to the degree of hypothermia suggests hypovolemia, hypoglycemia, or
      the presence of toxins. Given the decreased carbon dioxide production, persistent
      hyperventilation implies an underlying organic acidosis or central nervous system
      abnormality. Finally, toxic or traumatic or infectious impairment of the central
      nervous system may be obscured by hypothermia.

PMID- 16088599
TI  - Management of acute ischemic stroke.
AB  - Prior to 1995 no proven therapy existed for acute ischemic stroke. In 1996 the
      U.S. Food and Drug Administration approved the use of intravenous rt-PA in acute
      stroke based largely on the results of a two-part trial sponsored by the National
      Institutes of Health and National Institute of Neurological Disorders and Stroke
      (NIH/NINDS). Five years following approval, however, thrombolytic treatment
      remains underutilized, occurring in only 1 to 2% of all stroke patients. The
      medical community is now being called upon to organize systems capable of
      delivering acute stroke care in a time-urgent manner not previously contemplated.
      Critical care specialists may be called upon to treat stroke occurring in
      hospitalized patients or to continue care initiated in the emergency department.
      This article briefly reviews the pathogenesis of cellular injury in stroke and
      its initial evaluation and care and then focuses on the data involving
      thrombolytic reperfusion. Special attention is given to postthrombolytic critical
      care issues as these represent an important determinant in patient outcome.
      Secondary stroke prevention strategies and complication management are discussed
      along with general intensive care issues for the stroke patient.

PMID- 16088600
TI  - Rare or orphan lung diseases.

PMID- 16088601
TI  - Lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a rare disease categorized by an overgrowth of
      atypical smooth muscle cells (LAM cells) in the lungs and axial lymphatics, which
      is associated with the mesenchymal tumor angiomyolipoma. The disease occurs in
      women generally in their mid thirties with a prevalence approximately 1 per
      million in the general population but is much more frequent in women with
      tuberous sclerosis complex (TSC). LAM is categorized by airflow obstruction, lung
      cysts, recurrent pneumothorax, and pleural and abdominal chylous collections. The
      disease is progressive, generally resulting in respiratory failure and death. The
      TSC-2 gene is abnormal in LAM cells and may be responsible for their disordered
      growth. These cells are of an unusual phenotype, expressing smooth muscle
      proteins, melanoma proteins, estrogen and progesterone receptors. Although at
      present of unknown significance these are useful in diagnosis. Treatment is
      largely supportive, being directed at airflow obstruction, pneumothorax, chylous
      complications, and bleeding from angiomyolipomas. In patients with rapidly
      progressive disease, hormone manipulation is frequently tried in the form of
      progesterone or antiestrogen therapies although no firm evidence of their
      efficacy exists.

PMID- 16088602
TI  - Pulmonary Langerhans' cell histiocytosis.
AB  - Pulmonary Langerhans' cell histiocytosis (PLCH) remains an important diagnostic
      consideration in the differential diagnosis of diffuse infiltrative lung disease,
      particular among smokers. This review highlights recent progress in our
      understanding of the etiology, clinical presentation, and diagnostic and
      therapeutic approaches to this unusual lung disorder. Evolving studies strongly
      link the basic pathogenesis of PLCH as an uncommon reaction to tobacco smoke.
      Recent progress in the clinical approach to these patients has emphasized
      important roles for high-resolution computed tomographic (CT) scanning and immune
      reactive tissue markers including cluster differentiation (CD) 1a antigen in the
      diagnosis of this disorder. A rationale diagnostic algorithm and current
      management strategies are summarized.

PMID- 16088603
TI  - Pulmonary alveolar microlithiasis.
AB  - Pulmonary alveolar microlithiasis is a rare pulmonary disorder of unknown
      etiology characterized by intra-alveolar development and deposition of microliths
      or calcispherytes consisting of calcium phosphate. Approximately 400 cases of
      this rare disorder have been described in the literature. The age range of
      patients is from newborn to 80 years, with a mean age at diagnosis of about 35
      years. No sexual predominance has been noted. In about half of the reported
      cases, a familial pattern has been found, with the disease usually affecting the
      siblings. The progression of the disease is generally very slow, some patients
      having been followed up for more than 30 years without evidence of change.
      Pulmonary function studies demonstrate a tendency toward a restrictive pattern.
      Chest roentgenography, high-resolution computed tomographic chest scan, and
      technetium-99m lung scan are useful in the diagnosis. A definitive diagnosis can
      be established by bronchoalveolar lavage or lung biopsy. There is no known
      therapy for this unusual disorder. In patients who develop progressive
      respiratory insufficiency and cor pulmonale, lung transplantations have been
      performed.

PMID- 16088604
TI  - Pulmonary Alveolar Proteinosis: recent advances.
AB  - Pulmonary Alveolar Proteinosis (PAP) is characterized by the accumulation of
      surfactant phospholipids and proteins within the alveoli of lungs. Currently, no
      specific therapy exists for PAP, and sequential whole lung lavage is standard
      treatment. Over the past 5 years, important advances have been made in our
      understanding of alveolar proteinosis, offering new directions for research as
      well as patient management. First, genetically altered mice that are homozygous
      for a disrupted granulocyte-macrophage colony-stimulating factor (GM-CSF) gene
      developed a lung lesion with histologic resemblance to PAP, along with normal
      hematopoiesis. The biochemical properties of the material filling the airspaces
      in these mutant mice are similar to those of patients with PAP. Surfactant is
      thought to be cleared or catabolized mostly by alveolar macrophages, a process
      dependent on GM-CSF. Second, a neutralizing autoantibody against GM-CSF was found
      in bronchoalveolar lavage fluid and serum of patients with idiopathic PAP, but
      not healthy controls. These observations raise the previously unsuspected notion
      that human alveolar proteinosis may be an autoimmune disease, and suggest that GM
      CSF antibody has a potential role as a diagnostic test. The relationship between
      the antibody and disease pathogenesis remains unknown. Additional data suggest
      that exogenous therapy with GM-CSF may improve the lung disease in some patients
      with PAP. Intervention directed at treating a relative GM-CSF deficiency or
      lowering the antibody (i.e., by plasmapheresis or immunosuppression) may have
      promise in the therapy of this disease. Alveolar proteinosis may be the first
      human disease wherein a circulating antibody against a growth factor is linked to
      disease pathogenesis. Over a relatively short time, studies from ;;knock-out''
      mice have been translated to human studies for a new approach to diagnosis and
      therapy for this disease.

PMID- 16088605
TI  - The eosinophilic pneumonias.
AB  - Acute and chronic eosinophilic pneumonia can be distinguished by their clinical,
      laboratory, and radiographic features. Patients with both acute and chronic
      eosinophilic pneumonia present with cough, dyspnea, and fever. Patients with
      chronic eosinophilic pneumonia present subacutely over weeks to months but
      patients with acute eosinophilic pneumonia present within 5 days of symptom
      onset. Chest radiographs in chronic eosinophilic pneumonia show peripheral
      alveolar infiltrates. In contrast, radiographs in acute eosinophilic pneumonia
      show mixed interstitial and alveolar infiltrates, Kerley B lines, and pleural
      effusions. Both disorders are characterized by high percentages of
      bronchoalveolar lavage eosinophils, but high numbers of blood eosinophils
      accompanies only chronic eosinophilic pneumonia. The diagnosis of both disorders
      can usually be made based on clinical and radiographic findings; however, lung
      biopsy is occasionally necessary to distinguish the eosinophilic pneumonias from
      other eosinophilic lung diseases. In both conditions, patients will respond
      rapidly and completely to corticosteroids but patients with chronic eosinophilic
      pneumonia usually relapse if less than 6 months of treatment is given, whereas
      patients with acute eosinophilic pneumonia do not relapse after a brief course of
      treatment.

PMID- 16088606
TI  - Mediastinal granuloma and mediastinal fibrosis.
AB  - Mediastinal granuloma/mediastinal fibrosis is a chronic inflammatory disease of
      the mediastinum. Mediastinal granuloma is the abnormal enlargment of mediastinal
      lymph nodes by granulomatous inflammation, is usually asyptomatic or minimally
      symptomatic, and is often detected on chest radiographs taken for other reasons.
      In contrast, mediastinal fibrosis is extensive fibrous tissue throughout the
      middle mediastinum causing compression, encasement, or invasion of the large
      bronchi, superior vena cava, pulmonary veins, or esophagus, often with serious
      clinical consequences. Some patients may exhibit a clinical entity characterized
      by enlarged fibrotic and/or calicified lymph nodes with a variable amount of
      fibrosis that may be asymptomatic, or may cause symptoms by compression or
      invasion of structures in the mediastinum. Clinical manifestations may be due to
      superior vena cava (SVC) obstruction, esophageal compression, large airway
      involvement, pulmonary artery or pulmonary vein narrowing, or laryngeal or
      phrenic nerve impingement. Definitive diagnosis is traditionally made on the
      basis of a surgical exploration and biopsy, either a mediastinoscopy or
      thoracotomy; however, characteristic findings on computed tomography (CT) of the
      chest may be sufficient for a diagnosis in a certain number of cases. The best
      therapy is unknown. Antifungal therapy and corticosteroids have been reported
      effective in some cases. Surgical resection of localized mediastinal granuloma or
      fibrosis causing symptoms is often effective. However, surgical resection of
      extensive mediastinal fibrosis usually is not feasible.

PMID- 16088607
TI  - Relapsing polychondritis.
AB  - Relapsing polychondritis (RP) is a rare disease causing inflammation and
      destruction of cartilage and other connective tissues. Specific laboratory
      aberrations are lacking. Predominant clinical manifestations include auricular
      chondritis, polyarthritis, nasal chondritis, ocular inflammation, audiovestibular
      damage, and respiratory tract chondritis. A relapsing course is characteristic.
      Airways are involved in 50% of patients and may cause dyspnea, stridor, wheezing,
      hoarseness, aphonia, and laryneal or tracheal tenderness. Airflow obstruction may
      result from RP involving the tracheobronchial tree; there is no interstitial or
      pulmonary vascular component. Collapse or failure of the trachea to dilate during
      inspiration is a key feature. Fast computed tomographic (CT) scanners can
      visualize dynamic airway collapse. Randomized, controlled trials of therapy have
      not been done. Corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs)
      are used most commonly, but optimal regimens and duration of therapy have not
      been elucidated. Endobronchial stents or tracheostomy may be required for severe
      stenoses refractory to medical therapy.

PMID- 16088608
TI  - Pulmonary and tracheobronchial amyloidosis.
AB  - Amyloidosis is a collection of diseases in which different proteins are deposited
      as insoluble beta-pleated sheets, disrupting organ function. Each precursor
      protein induces a separate spectrum of organ involvement, and different disease
      manifestations within the lung. Although autopsy data often demonstrate amyloid
      deposits in various compartments of the lung, few of the pathologic findings are
      expressed clinically. We review the pulmonary pathology, radiology, clinical
      presentations, and treatment options for each of the major systemic and localized
      forms of amyloidosis. This review focuses on amyloid derived from immunoglobulin
      light-chain protein (AL disease), which most frequently involves the lung in both
      systemic and localized forms of the disease. Manifestations of AL-related lung
      disease range from nodules identified on incidental chest films to diffuse
      alveolar+-septal deposition mimicking diffuse alveolar damage. We discuss
      respiratory failure due to diaphragm invasion, proximal tracheal disease, and
      diffuse alveolar-septal deposition. Guidelines for evaluation of patients with
      amyloid are presented.

PMID- 16088609
TI  - Tracheobronchopathia osteochondroplastica.
AB  - Tracheobronchopathia osteochondroplastica (TPO) is an uncommon benign disease of
      unknown etiology characterized by multiple cartilaginous or bony submucosal
      nodules, which project into the tracheobronchial lumen. The nodules originate in
      the airway cartilages and thus typically spare the posterior membranous wall of
      the airways. The disorder is more common in men and the diagnosis is usually made
      in the fourth through sixth decades of life. There is no relationship to smoking
      or other systemic disorders. The disease is manifested by chronic cough and
      wheezing, which frequently lead to the mistaken diagnosis of asthma. Other
      pulmonary symptoms include dyspnea and hemoptysis. One of the complications is
      the increased incidence of recurrent respiratory infections. The pulmonary
      symptoms and complications are the consequence of narrowing and thickening of the
      airway walls. Even though roentgenologic imaging studies may indicate the
      diagnosis, bronchoscopy is the most definitive diagnostic test. The bronchoscopic
      appearance alone is diagnostic of the disease, and biopsy of the airway lesions
      is seldom, if ever, required. Although there is no specific therapy for this
      disorder, management of tracheobronchopathia osteochondroplastica includes
      bronchodilators, prompt treatment of pulmonary infections, and bronchoscopic
      dilatation when indicated.

PMID- 16088610
TI  - Genetics of pulmonary fibrosis.
AB  - Pulmonary fibrosis is a devastating disease that occurs in association with
      environmental exposures, several inherited diseases, collagen vascular disease,
      as well as in an idiopathic form. Epithelial cell damage, excessive fibroblast
      proliferation, upregulation of extracellular matrix production, and attenuated
      matrix degradation are shared pathophysiological features of these different
      forms of pulmonary fibrosis. Several observations suggest that genetic
      predisposition plays an important role in the pathophysiology of pulmonary
      fibrosis. There is significant inter-individual variation in the degree of
      pulmonary fibrosis resulting from exposure to similar levels of an inhaled
      fibrogenic agent. There are several inherited diseases with known genetic
      mutations that have high rates of pulmonary fibrosis. Idiopathic pulmonary
      fibrosis can occur in multiple first-degree relatives, including those separated
      at an early age. Finally, recent studies have identified polymorphisms within
      genes for cytokines, histocompatability antigens, and extracellular matrix
      components that are associated with the development of pulmonary fibrosis.
      Identification of putative pulmonary fibrosis gene/s (PF gene/s) may result in
      novel diagnostic and therapeutic interventions for those at risk for development
      of pulmonary fibrosis.

PMID- 16088611
TI  - Overview of neuromuscular disorders affecting respiratory function.
AB  - A great many neuromuscular disorders affect respiratory function. This article
      focuses on neuropathic and myopathic disorders that weaken the diaphragm and
      respiratory muscles. This discussion gives a general overview and attempts to
      update the reader on recent pathophysiological insights and developments in
      therapy. Among the disorders discussed, amyotrophic lateral sclerosis,
      poliomyelitis, postpolio syndrome, Kennedy syndrome, and spinal muscular atrophy
      are motor neuron diseases. Brachial plexitis and isolated unilateral or bilateral
      phrenic neuropathies can also weaken the diaphragm significantly. Peripheral
      neuropathies affecting respiration are primarily acute disorders such as Guillain
      Barre syndrome, porphyria, and critical illness neuropathy, but chronic diseases
      such as chronic inflammatory demyelinating polyneuropathy (CIDP) and Charcot
      Marie-Tooth disease (CMT) can also cause respiratory insufficiency. Disorders of
      neuromuscular transmission such as Lambert-Eaton syndrome, botulism, and
      myasthenia gravis often affect respiration. Many muscle diseases also affect
      pulmonary function, including polymyositis/dermatomyositis, muscular dystrophy,
      hereditary channel disorders, mitochondrial encephalomyopathies, acid maltase
      deficiency, and congenital myopathy.

PMID- 16088612
TI  - Respiratory muscle evaluation of the patient with neuromuscular disease.
AB  - This review presents clinically relevant issues regarding the assessment of
      respiratory muscles in individuals with neuromuscular disorders, and discusses
      the advantages and disadvantages of methods generally available to the clinician.
      Vital capacity (VC) and total lung capacity (TLC) are routinely measured in
      pulmonary function laboratories and are typically reduced in the context of
      severe respiratory muscle weakness, but the sensitivity and specificity of these
      measures are limited. Better measures of respiratory muscle weakness are maximal
      static inspiratory and expiratory pressures (PI max and PE max). PI max is
      reduced even with mild or moderate degrees of inspiratory muscle weakness, but
      low values also may be related to submaximal effort. To circumvent this problem,
      pressures can be measured using simpler maneuvers such as a maximal sniff.
      Specific tests of diaphragm function such as measurements of maximal
      transdiaphragmatic pressure are invasive and not routinely available to the
      clinician. Recently, noninvasive methods that specifically assess diaphragm
      function, such as diaphragm ultrasound of the zone of apposition and magnetic or
      electrophrenic nerve stimulation, have shown promise as new techniques for
      clinical use.

PMID- 16088613
TI  - Sleep abnormalities associated with neuromuscular disease: pathophysiology and
      evaluation.
AB  - The development of respiratory failure is common in patients with neuromuscular
      disorders that involve the respiratory muscles. However, the high incidence of
      sleep-related breathing problems in this population is less well known. In
      patients with neuromuscular disease, nocturnal breathing abnormalities frequently
      precede respiratory failure during wakefulness by months or even years. These
      nocturnal breathing problems are caused by multiple factors, including diaphragm
      and upper airway muscle weakness, scoliosis, obesity, and central respiratory
      control problems. Advances in the understanding of the links between sleep
      disordered breathing and the development of daytime dysfunction and respiratory
      failure has revolutionized the management of these individuals. Mask positive
      pressure therapy is now available to improve both quality of life and longevity
      for these individuals. The lack of correlation between daytime testing and the
      severity of nocturnal breathing abnormalities makes it difficult to predict the
      presence of sleep-disordered breathing. Further, patients may not always be aware
      of symptoms associated with sleep-disordered breathing, even if specifically
      questioned. However, simple bedside measurements of vital capacity and
      inspiratory muscle strength can provide useful guides for when nocturnal
      respiratory monitoring is indicated.

PMID- 16088614
TI  - Respiratory complications of rapidly progressive neuromuscular syndromes:
      Guillain-Barre syndrome and myasthenia gravis.
AB  - Neuromuscular respiratory failure is a common complication of both the Guillain
      Barre syndrome and myasthenia gravis. Several key pathophysiological mechanisms
      contribute to the spiral of respiratory insufficiency in these diseases,
      including inspiratory, expiratory, and bulbar muscle weakness. It is important to
      identify patients with impending respiratory failure early to avoid emergency
      intubations. Several clinical features and bedside pulmonary function tests
      (PFTs) are useful in guiding decisions about intubation. Weaning is initiated
      when respiratory muscles have recovered sufficiently, and again, PFT criteria are
      helpful. Intravenous immunoglobulin and plasmapheresis are the cornerstones of
      specific therapy for both illnesses when complicated by respiratory failure.
      Mortality and morbidity are dramatically increased by respiratory failure and are
      mainly due to associated medical complications. Optimal outcomes depend on
      avoidance of these and prompt implementation of immunomodulatory therapy.

PMID- 16088615
TI  - Respiratory complications of the muscular dystrophies.
AB  - Pulmonary complications including chest infections, atelectasis, pulmonary
      hypoplasia and ventilatory failure are the leading cause of death in the muscular
      dystrophies and atrophies. Ventilatory insufficiency is virtually inevitable in
      Duchenne muscular dystrophy and type 1 spinal muscular atrophy (SMA), but more
      variable in limb-girdle, congenital, and facioscapulohumeral muscular dystrophy.
      A cardiomyopathy may complicate Duchenne, Becker, and Emery-Dreifuss muscular
      dystrophies. Most patients respond well to ventilatory support with reduced
      pulmonary morbidity and extended survival. Careful monitoring and anticipation of
      complications are important so that ventilatory assistance can be started in a
      timely fashion.

PMID- 16088616
TI  - Respiratory complications of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      with no known cure. Involvement of muscles of the respiratory system, the
      inspiratory, expiratory, and upper airway muscles, is the major cause of
      morbidity and mortality. Dyspnea, swallowing difficulties, sialorrhea, and
      impaired cough are all symptoms that can be palliated with pharmacological and
      nonpharmacological methods. Noninvasive positive pressure ventilation (NPPV) in
      particular is a technique to assist ventilation that not only relieves dyspnea
      and ameliorates respiratory failure but may also extend the lives of patients
      with this disease. It should be offered to all ALS patients with a forced vital
      capacity of less than 50%.

PMID- 16088617
TI  - Respiratory complications of stroke.
AB  - Stroke is the third leading cause of death in the United States. Stroke survivors
      often experience medical complications and long-term disability. Disturbances in
      respiratory system function and complications affecting the respiratory system
      are common after stroke. The nature of these disorders depends on the severity
      and site of neurological injury. Alterations in breathing control, respiratory
      mechanics, and breathing pattern are common and may lead to gas exchange
      abnormalities or the need for mechanical ventilation. Stroke can lead to sleep
      disordered breathing such as central or obstructive sleep apnea. Sleep disordered
      breathing may also play a role in the pathogenesis of cerebral infarction. Venous
      thromboembolism, swallowing abnormalities, aspiration, and pneumonia are among
      the most common respiratory complications of stroke. Neurogenic pulmonary edema
      occurs less often. Close observation of the stroke patient for these potential
      disturbances, and implementation of prophylactic measures can prevent significant
      morbidity and mortality.

PMID- 16088618
TI  - Respiratory complications of Parkinson's disease.
AB  - Patients with Parkinson's disease are at risk for pulmonary complications as a
      consequence of both the underlying disease pathology and the side effects of
      medication. Degeneration of the substantia nigra and subsequent loss of
      dopaminergic neurons may produce changes in ventilatory parameters. Upper airway
      obstruction and chest wall restriction are both common, and both may respond to
      levodopa. However, therapy for Parkinson's may also contribute to pulmonary
      morbidity. Overtreatment with levodopa causes respiratory dyskinesia that may be
      difficult to differentiate from complications of the disease itself. Therapy with
      ergot derivatives may cause pleuropulmonary fibrosis. Pneumonia resulting from
      the respiratory complications remains a significant cause of morbidity and
      mortality in Parkinson's disease.

PMID- 16088619
TI  - Respiratory complications of poliomyelitis and multiple sclerosis.
AB  - Years after suffering from poliomyelitis and completely recuperating from any of
      its acute complications, patients can develop postpolio syndrome (PPS), thought
      to be caused by progressive neuronal loss. The symptoms and manifestations of PPS
      vary in intensity and distribution, but many patients have respiratory
      involvement and will require a pulmonary evaluation for new or increased dyspnea,
      fatigue, or symptoms suggestive of sleep-related disordered breathing. The
      diagnosis, evaluation, and management of this complex problem are discussed in
      the first part of this article. In the second part, pulmonary complications of
      multiple sclerosis are described. This common neurological disease affects young
      adults and often requires evaluation by a pulmonologist. This review centers on
      the acute respiratory manifestations of multiple sclerosis and also describes the
      chronic effects.

PMID- 16088620
TI  - Respiratory management of diaphragm paralysis.
AB  - The diaphragm is the most important muscle of ventilation. Its contraction is key
      to the development of intrathoracic pressures. Diseases that affect diaphragmatic
      function result in decreased pressure-generating capacity by the respiratory
      muscles. If the involvement is severe or if there is underlying respiratory
      pathology, diaphragmatic paralysis can lead to overt ventilatory failure.
      Diaphragmatic involvement can occur unilaterally or bilaterally from systemic
      diseases or from diseases primarily affecting the diaphragm. Whatever the cause,
      unilateral diaphragmatic paralysis is usually well tolerated if there is no
      underlying lung or ribcage pathology. However, under conditions of increased
      loads, unilateral diaphragmatic paralysis can cause dyspnea and hypoxemia and
      require treatment. Bilateral diaphragmatic paralysis of any etiology is usually
      symptomatic and may result in ventilatory failure when severe, or when associated
      with underlying lung pathology. In some patients unilateral or bilateral
      paralysis can improve spontaneously but usually over prolonged periods of time.
      In patients with significant symptoms or development of ventilatory failure,
      symptoms and outcomes are improved by treatment with noninvasive ventilation or,
      in selected cases of unilateral paralysis, surgical plication of the diaphragm.

PMID- 16088621
TI  - Continuous noninvasive ventilation for patients with neuromuscular disease and
      spinal cord injury.
AB  - Patients with a variety of neuromuscular diseases including quadraplegia due to
      high spinal cord lesions can be managed with full-time noninvasive ventilation
      instead of intermittent positive pressure ventilation (IPPV) via a tracheostomy.
      This approach is not suitable for patients with severe bulbar involvement. To be
      successful with full-time noninvasive IPPV, the ventilator user must realize
      three goals. First, respiratory system compliance should be optimized and
      maintained by frequent full inflations delivered by stacking breaths from a
      volume-cycled ventilator or by insufflating air at adequate pressures using a
      mechanical insufflator-exsufflator. Second, normal levels of alveolar ventilation
      are sustained using a variety of noninvasive approaches, including nasal,
      oronasal, or mouthpiece interfaces. Third, patients must be taught to use
      techniques and devices to enhance cough, particularly the mechanical insufflator
      exsufflator. When these goals are met, noninvasive NPPV can offer patients
      greater comfort, simpler and more convenient ventilator use, and reduced rates of
      infections, complications, and hospitalizations as compared with tracheostomy
      IPPV.

PMID- 16088622
TI  - Ventilator management for neuromuscular disease.
AB  - Many progressive neuromuscular disorders involve the muscles of the respiratory
      system, and respiratory insufficiency is a major cause of morbidity and
      mortality. Thus ventilatory assistance becomes an important part of disease
      management for patients with advanced neuromuscular disease. The following
      discusses the evaluation of patients with neuromuscular disease to characterize
      the nature and severity of respiratory muscle involvement, indications and
      contraindications for the use of noninvasive ventilation, and techniques for
      initiation and monitoring. Indications for invasive ventilation are also
      discussed, and major principles of management and monitoring of invasive
      mechanical ventilation are outlined. For optimal ventilator management of
      patients with neuromuscular disease, clinicians must be familiar with the
      principles discussed in this article so that treatment can be tailored to the
      individual's goals and desires. With proper implementation, ventilatory support
      of patients with neuromuscular disease can bring about improvements in quality of
      life and, for those who desire, potential prolongation of survival.

PMID- 16088623
TI  - Ethical issues in the long-term management of progressive degenerative
      neuromuscular diseases.
AB  - Degenerative neuromuscular diseases are characterized by a gradual decline of
      motor function leading to respiratory collapse, while the patients retain
      consciousness and cognition. The ethical challenges of caring for such patients
      result from the need to implement various combinations of initiating,
      withholding, and withdrawing life-sustaining interventions. In caring for this
      population of patients physicians should adhere to the ethical principles of
      autonomy, beneficence, nonmaleficence, and justice. A central goal of care is to
      avoid a decisional impasse by anticipating end-of-life issues in discussion with
      patients and families. The evolution of these diseases is usually slow enough to
      allow ample patient education, and thus physicians should foster early and frank
      discussions and encourage the patient to set up advance directives, designate a
      durable power of attorney for health care, and plan end-of-life care. Competent
      patients have the right to accept or refuse life-sustaining therapies, and such
      requests should be honored. In delivering palliative care, adequate sedation and
      analgesia must be provided when needed. If a decision to withhold or withdraw
      life support is made, patient comfort and dignity are the ultimate objectives.

PMID- 16088624
TI  - Asthma.

PMID- 16088625
TI  - Epidemiology of asthma.
AB  - There is no illness more in need of epidemiological study than asthma. Despite
      significant advances in our understanding of the pathophysiology, course, and
      management of this disease, its prevalence, morbidity, and mortality appear to be
      on the rise, and the reasons are not entirely clear. Historically,
      epidemiological studies of asthma have suffered from the lack of a standardized
      definition of the disease and the lack of a ;;gold standard'' with which to
      compare objective measures for diagnosing the illness. Recent studies have
      overcome some of these difficulties to provide solid epidemiological data on
      asthma from a global perspective. International studies have demonstrated that
      asthma prevalence varies significantly worldwide, with Western, English-speaking
      countries having the highest prevalence rates. In the United States, the
      prevalence of asthma has increased by nearly 75% in the past 2 decades. Young
      children, blacks, and Hispanics tend to be disproportionately affected by the
      disease. Asthma morbidity, as measured by emergency department visits,
      hospitalizations, and medication usage has been increasing worldwide, and asthma
      mortality, although still rare, has been increasing as well. Epidemiological
      studies have provided important information regarding the etiology and risk
      factors for asthma. The disease is emerging as a prototypical illness for the
      alliance of genetic and environmental disease determinants. Some of the most
      important conclusions relate to the developing immune system and the timing of
      certain allergic or infectious exposures that may predispose the child to develop
      asthma. Indeed, advances in epidemiological study will be critical if we are to
      intervene and reverse some of asthma's disturbing trends.

PMID- 16088626
TI  - The genetics of asthma.
AB  - Asthma is a complex respiratory disease that, based on familial aggregation
      studies, has long been recognized to have a significant genetic component.
      Understanding the genetics of asthma is complicated by the fact that there are
      multiple different pathophysiological mechanisms leading to a complicated
      heterogeneous phenotype that is difficult to define. It is generally recognized
      as a complex genetic disease that cannot be explained by single gene models, and
      in most cases it appears to result from the interaction of multiple genetic and
      environmental factors. Although linkage and association studies have demonstrated
      several important relationships between asthma and a variety of genetic loci, no
      single gene or group of genes has been definitively demonstrated to be
      responsible for asthma. However, population studies, candidate gene approaches,
      genome-wide screens, and pharmacogenetic studies have all resulted in an
      increased understanding of the complexities of asthma genetics and may lead to
      better preventive strategies, diagnostic tools, and therapies for this disease.

PMID- 16088627
TI  - Infections and asthma.
AB  - Infections have a variety of influences in the asthmatic patient. Respiratory
      syncytial virus (RSV) is the most common cause of wheezing illnesses in children
      under the age of 2 years and may be a risk factor for the inception of asthma in
      the first decade of life. Once asthma has become recognized clinically,
      rhinovirus is the leading cause of acute asthma exacerbations in adults and older
      children. Certain respiratory infections may induce chronic lower airway
      inflammation that may contribute to disease progression or severity in asthma.
      Paradoxically, some infections may even protect against the development of
      asthma. This article reviews the evidence for these associations and the
      mechanisms proposed to explain these various outcomes.

PMID- 16088628
TI  - The role of the distal lung in asthma.
AB  - Accumulating patholological and physiological evidence in the last few years
      suggests that the airway inflammation and remodeling that characterize asthma
      occur not only in the central airways but extend to the distal lung and the lung
      parenchyma. The distal airways are capable of producing T-helper (Th)2 cytokines
      as well as chemokines, and more recently, they have been recognized as a
      predominant site of airflow obstruction in asthmatics. A similar TH2-type
      cytokine profile and infiltration of inflammatory cells has also been reported in
      the lung parenchyma. The inflammation at this distal site has been described as
      more severe when compared with the large airway inflammation, and evidence of
      remodeling in the lung periphery is emerging. Recognition of asthma as a disease
      of the entire respiratory tract has an important clinical significance
      highlighting the need also to consider the distal lung as a target in any
      therapeutic strategy for effective treatment of this disease.

PMID- 16088629
TI  - Airway remodeling in asthma.
AB  - Airway remodeling is a summary term for the pathological changes that occur in
      airway structure in allergic or suppurative airway diseases. Characteristic
      changes of airway remodeling in asthma include goblet cell hyperplasia,
      deposition of collagens in the basement membrane zone, increased size and number
      of microvessels in the submucosa, hyperplasia and hypertrophy of airway smooth
      muscle, and hypertrophy of submucosal glands. Some of these changes, such as
      goblet cell hyperplasia and subepithelial collagen deposition, are present even
      in mild asthma; other changes such as increases in airway smooth muscle and gland
      volume appear to be more characteristic of severe asthma. Airway narrowing,
      airway hyperresponsiveness, and mucus hypersecretion are all functional
      consequences of airway remodeling leading to clinical manifestations such as
      dyspnea, wheeze, sputum production, and susceptibility to asthma exacerbations.
      Noninvasive measures of remodeling are lacking, and monitoring the effects of
      treatment on remodeling has been difficult. For this reason relatively little is
      known about the effects of current asthma treatments on airway remodeling. As
      mechanisms of airway remodeling are developed, it is hoped that novel therapeutic
      targets will be identified. Treatments specifically targeting mediators of
      remodeling hold promise as treatments that could modify disease progression in
      asthma.

PMID- 16088630
TI  - Beta2-agonists: friend or foe?
AB  - This review summarizes the effects of beta2-agonists on asthma severity. There
      has been a controversy as to whether the regularly scheduled use of beta2
      adrenergic agonists increases the risk of adverse outcomes in asthma. A number of
      epidemiological and clinical studies have found an association between the
      regularly scheduled use of beta-agonist drugs and increased risk of asthma
      morbidity and mortality. However, this observation has not been consistent across
      studies. We discuss here the potential mechanisms to explain the relationship
      between the use of beta-agonists on a regularly scheduled basis and adverse
      outcomes of asthma therapy; and we provide a brief review of the effect of
      genetic diversity at the beta2-adrenergic receptor locus on asthma severity.
      Overall, the evidence suggests that the beta2-agonists in current use in the
      United States are generally safe and effective; friends, not foes.

PMID- 16088631
TI  - Inhaled steroids: are they all created equal?
AB  - New inhaled steroids or new formulations of inhaled steroids continue to be
      introduced on a regular basis in an attempt to replace hydrochlorofluorocarbon
      propellant-based, pressurized, metered dose delivery systems. New delivery
      systems are being introduced with either a replacement propellant in a
      pressurized metered dose inhaler, such as a hydrofluoroalkane, or a dry powder,
      breath-actuated delivery device. Although there are now many different steroid
      preparations and delivery devices available, little is known about their relative
      beneficial and adverse effects. Several recent studies have introduced methods to
      determine the comparative efficacy of different inhaled steroids as related to a
      standardized measure of systemic effect. Physicians should be familiar with the
      differences among the available choices of inhaled steroid-delivery device
      combinations in order to select therapy that will optimize response and minimize
      the risk for adverse effects.

PMID- 16088632
TI  - Steroid-unresponsive asthma.
AB  - Although most patients with chronic asthma respond to corticosteroid therapy, a
      small subset of asthmatics are unresponsive to corticosteroids and demonstrate
      persistent airway obstruction and inflammation despite treatment with high doses
      of systemic glucocorticoids. There are at least two types of steroid-resistant
      asthma. Type I steroid-resistant (SR) asthma is cytokine induced and is
      associated with increased expression of glucocorticoid receptor beta, a less
      active glucocorticoid receptor isoform. Type II SR asthma is due to low numbers
      of glucocorticoid receptors. An important distinction between these two types of
      SR asthma is that the glucocorticoid receptor defect in Type I, but not Type II,
      SR asthma is reversible in culture and is sustained by incubation with
      combination interleukin (IL)-2 and IL-4. The treatment of these patients requires
      a systematic approach to rule out underlying conditions that lead to steroid
      resistance or treatment failure as well as the use of alternative strategies to
      inhibit airway inflammation.

PMID- 16088633
TI  - Leukotriene receptor antagonists.
AB  - In the past decade, heightened emphasis has been placed on the importance of
      inflammation in the pathogenesis of asthma. Although corticosteroids have
      remained the primary anti-inflammatory agents in the management of the persistent
      asthmatic, new classes of drugs have recently been added. The leukotriene
      receptor antagonists (LTRAs) are the first new approach in asthma therapy in the
      past 25 years and the first class of drugs to target specific components of the
      inflammatory process. These drugs reverse the primary biological effects of the
      cysteinyl leukotrienes in relation to the pathogenesis of asthma including
      bronchoconstriction, mucus hypersecretion, and airway inflammation. The LTRAs
      have demonstrated efficacy against exercise- and allergen-induced
      bronchoconstriction, aspirin-sensitive asthma, and additive benefit in
      symptomatic moderate asthmatics on maintenance inhaled corticosteroids, as well
      as potential steroid-sparing effects. Finally, although evidence for their role
      as first-line controller agents for the management of mild persistent asthma has
      grown stronger in recent years, this role continues to evolve.

PMID- 16088634
TI  - Hospital-acquired pneumonia.

PMID- 16088635
TI  - Epidemiology and microbiology of hospital-acquired pneumonia.
AB  - Hospital-acquired pneumonia (HAP) is the second most common nosocomial infection
      in the critically ill patient and is associated with the greatest mortality and
      increased morbidity and cost of care. The major risk factor for the development
      of HAP in intensive care is the occurrence of intubation and mechanical
      ventilation, giving rise to the term ventilator-associated pneumonia (VAP).
      Incidence of VAP varies in different populations of critically ill patients and
      generally ranges from 9 to 20%, with an overall rate of 10 to 15 cases per 1,000
      ventilator days. The cumulative risk of developing VAP is ~1% per day of
      mechanical ventilation (MV). The crude mortality rate of VAP is 60% and the
      estimates of attributable risk range from 27 to 43%. Mortality from VAP is
      influenced by host factors, the virulence of the pathogens, and the adequacy of
      initial antimicrobial therapy. The etiologic agents for VAP differ according to
      the population studied, duration of hospital stay, time after intubation, and
      prior antimicrobial therapy. Risk factors include nonmodifiable factors like age,
      chronic obstructive pulmonary disease, severe head trauma, and multiple trauma,
      and modifiable factors like large volume gastric aspiration, duration of MV,
      elevated gastric pH, histamine type 2 blocker therapy, ventilator circuit change
      frequency, self-extubation, and reintubation. The impact that diagnosis using
      invasive diagnostic techniques may have on the epidemiological characteristics of
      VAP are unknown, but may potentially reduce problems resulting from
      misclassification of this entity.

PMID- 16088636
TI  - The pathogenesis of ventilator-associated pneumonia.
AB  - Of the four routes of infection pathogenic bacteria can take, the inhalation and
      aspiration ones are the most important. Inhalation pneumonia is usually due to
      manipulation of the ventilator tubing and aspiration of the infected condensate.
      Aspiration of the colonized oropharyngeal contents through the open vocal cords
      and eventually around the blown up endotracheal cuff allows bacteria to invade
      the trachea and main bronchi. Reflux of the bacteria and infection of the biofilm
      on the inner surface of the endotracheal tube is the source for recurrent seeding
      of pathogenic bacteria into the lungs, causing ventilator-associated pneumonia.

PMID- 16088637
TI  - Pneumonia in head-injured and severe trauma patients.
AB  - Trauma is the leading cause of death in young people. Trauma deaths have a
      classic trimodal distribution; in late death (3 days to 3 weeks postinjury),
      infection is the principal cause. Because pneumonia is a major cause of morbidity
      in trauma patients, early identification of subjects at a high risk of developing
      nosocomial pneumonia (NP) can reduce morbidity and costs. Methicillin-sensitive
      Staphylococcus aureus (MSSA) is the predominant pathogen in multiple-trauma
      patients in coma, and nasal MSSA colonization at time of severe injury may
      increase the risk of MSSA pneumonia. In the remaining patients, gram-negative
      bacilli are responsible for the majority of cases. Prolonged mechanical
      ventilation, continuous enteral feeding, and craniotomy are risk factors for NP
      in trauma patients. Diagnosis of NP in these patients is difficult because
      radiographic infiltrates may not highlight any infection. In coma patients,
      coverage with a beta-lactam active against MSSA is mandatory. Variations in
      organisms and sensitivities across intensive care units due to differences in
      demographic characteristics or comorbidities should be considered.

PMID- 16088638
TI  - Pneumonia complicating the acute respiratory distress syndrome.
AB  - Ventilator-associated pneumonia (VAP) complicating the course of acute
      respiratory distress syndrome (ARDS) is one of the most challenging diagnostic
      and treatment dilemmas in critical care medicine. The VAP incidence rate ranges
      from 37 to 60% in ARDS patients, significantly greater than for other causes of
      respiratory failure. Although the normal risk factors for VAP are the same in
      ARDS patients, multiple aspects of the underlying disease and its management
      increase the risk compared with non-ARDS patients. Multiple mimics of the
      clinical symptoms and signs make the clinical diagnosis of VAP very nonspecific
      in the setting of ARDS. The multilobar but predominantly lower lobe pattern of
      pneumonia in ARDS makes use of quantitative cultures of lower respiratory
      secretions (sampled by various techniques) very accurate to confirm the presence
      of pneumonia. VAP in ARDS patients is usually late-onset and therefore caused by
      highly antibiotic-resistant microorganisms. Somewhat surprisingly, the mortality
      of ARDS patients with VAP is not significantly greater than that of ARDS patients
      without VAP, although subsequent duration of mechanical ventilation is
      consistently prolonged in patients with VAP.

PMID- 16088639
TI  - Evolution of antimicrobial resistance: impact on antibiotic use.
AB  - During the past 50 years, the permanent increase in bacterial resistance to
      antibiotics has led to modifications in therapeutic recommendations. Despite
      evidence that antimicrobial exposure of human populations is the most important
      driving force for the continuous increase in bacterial resistance, the studies of
      the impact of bacterial resistance on antibiotic use have, during the past,
      focused on clinical efficacy of individual treatments rather than on collective
      control of resistance. There are current changes in this attitude, mainly in
      hospitals, probably because hospital prescribers have experienced the
      consequences of resistance on their patients. However, in the community such an
      awareness is not likely to develop in the near future. Therefore, there is a need
      for public health decision makers to become more involved in prevention of the
      impact of resistance in antibiotic use.

PMID- 16088640
TI  - Guidelines for treatment of hospital-acquired pneumonia.
AB  - In the past decade, much information has been gained on the diagnostic and
      therapeutic strategies in patients suspected of having hospital-acquired
      pneumonia. The key to an effective therapeutic approach is the diagnostic
      strategy used, and timely administration of appropriate antibiotic therapy. Many
      patients, but not all, need early appropriate empiric therapy. This decision and
      the selection of the initial regimen is based on local epidemiological and
      surveillance data, the clinical presentation, and the recent history of the
      individual patient; direct examination of reliable respiratory tract samples can
      provide a valuable help, but cannot be relied on solely. Whenever possible, the
      timely performance of such samples (i.e., before instituting therapy) is of
      paramount importance because this will bear heavily on their interpretation and
      the conduct of subsequent and definitive therapy. Hospitals are now plagued with
      infection caused by increasingly multidrug-resistant organisms; this is
      especially the case in intensive care units (ICUs), where nosocomial respiratory
      tract infection is the primary reason for prescribing antibiotics. Although many
      questions remain unanswered regarding the optimal choices and duration of
      therapy, reversing this trend will require continuous and prolonged efforts to
      strictly adhere to a rigorous approach for antibiotic prescribing in nosocomial
      respiratory tract infection.

PMID- 16088641
TI  - What is the natural history of resolution of nosocomial pneumonia?
AB  - Little is known about the natural history of resolution of nosocomial pneumonia,
      and thus it is likely that we are not always using the optimal duration of
      therapy in all patients. For some patients, with few risk factors for a poor
      outcome, and infection with easily treated pathogens, we can probably treat with
      a more abbreviated course of therapy than is commonly used. For other patients
      with risk factors for a poor outcome, and infection with ;;high risk'' pathogens
      such as Pseudomonas aeruginosa, we may need longer durations of therapy. We
      review the clinical and microbiological definitions of resolution, including
      improvement, delayed resolution, relapse, or recurrent infection. There are also
      microbiological end points for resoution including eradication, persistence, and
      superinfection. The clinical parameters that affect resolution are patient
      related, microbiological, and treatment related, and these factors are summarized
      here. Currently, the time course of resolution is being defined using clinical
      end points such as the clinical pulmonary infection score (CPIS) and
      microbiological end points such as quantitative cultures of respiratory
      secretions. The hope for the future is to be able to identify whether the
      clinical response is adequate, at the earliest posible time point. This may allow
      for interventions to help the nonresponding patient, or shorten the duration of
      therapy in the responding patient.

PMID- 16088642
TI  - Strategies for prevention of hospital-acquired pneumonia: oral and selective
      decontamination of the gastrointestinal tract.
AB  - The use of antimicrobial prophylaxis is the most extensively studied, though
      probably also the most controversial, method to prevent the development of
      ventilator-associated pneumonia (VAP). Selective decontamination of the digestive
      tract (SDD) includes the application of topical nonabsorbable antibiotics in the
      oropharynx, stomach, and intestines in combination with systemic antibiotics
      during the first days of ventilation. Multiple individual studies as well as
      seven meta-analyses have demonstrated that antimicrobial prophylaxis effectively
      reduces the incidence of VAP. However, oral decontamination may be as effective
      as the full SDD regimen in reducing the incidence of late-onset VAP. Moreover,
      the significant reductions in incidences of VAP have, so far, not resulted in
      reductions of duration of ventilation and ICU-stay, and reductions in ICU
      mortality were found only in meta-analysis. Selection of resistant bacteria is
      the most important drawback of antimicrobial prophylaxis, and the demonstrated
      benefits of antimicrobial prophylaxis should be carefully balanced with this
      potential risk.

PMID- 16088643
TI  - Nonpharmacological prevention of hospital-acquired pneumonia.
AB  - Hospital-acquired pneumonia (HAP) is the most common nosocomial infection
      occurring among mechanically ventilated patients. The benefits associated with
      the systematic prevention of HAP include fewer infections with high-risk
      antibiotic-resistant bacteria, lower rates of hospital mortality, reduced medical
      care costs, and shorter hospital lengths of stay. Unfortunately, many hospitals
      do not have an organized approach to the prevention of HAP. This review will
      describe the nonpharmacological approaches available for the prevention of HAP.
      It should help clinicians to design their own strategies for the prevention of
      this important hospital-acquired infection.

PMID- 16088644
TI  - Antibiotic utilization strategies to limit antimicrobial resistance.
AB  - Antimicrobial resistance is now being recognized as a major factor determining
      morbidity, mortality, and cost in the intensive care unit (ICU). Various
      strategies to limit its spread have evolved with our understanding and are based
      on four basic principles: infection prevention, infection eradication,
      containment of resistant species, and optimization of antibiotic utilization. The
      optimization of antibiotic utilization, at its most basic level, is the
      appropriate use of antibiotics and the limitation of unnecessary antibiotic
      administration/exposure consisting of appropriate diagnosis, acquiring
      appropriate culture and sensitivity data, implementing the most appropriate
      treatment, selecting appropriate antibiotics, and dosing appropriately. In
      addition various antibiotic utilization strategies including antibiotic
      utilization guidelines, formulary restriction, and antibiotic cycling or rotation
      have evolved from our understanding of the impact of changes in antibiotic
      utilization on subsequent antibiotic susceptibility patterns. These strategies
      can be utilized as a part of a multidisciplinary approach to limit the appearance
      and dissemination of antimicrobial resistance in our ICUs.

PMID- 16088645
TI  - Extrapulmonary sarcoidosis.

PMID- 16088646
TI  - Neuromuscular sarcoidosis.
AB  - Neuromuscular sarcoidosis is recognized with increasing frequency. Although
      reported to occur in only 5% of patients with sarcoidosis, major centers are
      reporting up to 20% neuromuscular involvement. While the majority of patients
      with neurologic involvement present with 7 (th) nerve palsy, the reported
      frequency of sarcoidosis of the brain, meninges, spinal cord, and muscles is
      rising. The diagnosis of neuromuscular sarcoidosis is usually accepted when a
      patient with previous biopsy-proven sarcoidosis presents with a compatible
      neurologic syndrome. In addition to cranial nerve abnormalities, these syndromes
      include leptomeningitis, seizures, mass lesions of brain and spinal cord,
      pituitary dysfunction, and neuropathies. Occasionally, the typical intrathoracic,
      ocular, cutaneous and lymph node presentations of sarcoidosis are not present or
      are unrecognized and the diagnosis is established by biopsy of neuromuscular
      tissue. Biopsy exhibiting granulomas is not specific and requires absence of
      evidence of known granulomagenic agents plus presence of multiorgan disease. An
      isolated granuloma in neural tissue without other organ involvement is not
      diagnostic of sarcoidosis. Treatment of neuromuscular sarcoidosis is usually
      prolonged. Facial palsy often improves spontaneously. Prednisone is still the
      drug of choice. Most authorities agree that 30 to 40 mg qd is sufficient with
      concomitant azathioprine or cyclophosphamide.

PMID- 16088647
TI  - Cardiac involvement in sarcoidosis.
AB  - Cardiac sarcoidosis is a challenging diagnostic entity. Manifestations range from
      an incidentally discovered, benign condition to fatal cardiomyopathy and
      arrhythmias. In this review, we discuss the salient clinical features, diagnostic
      evaluation, treatment, and prognosis of cardiac sarcoidosis. A definitive
      histologic diagnosis of myocardial sarcoidosis is difficult, and treatment may be
      necessary in some patients with suspected cardiac involvement even in the absence
      of histologic confirmation. Optimal strategies to diagnose cardiac involvement
      have not been clarified. Thallium (201) radionuclide scintigraphy has been most
      extensively studied; 2-D echocardiography is less sensitive, but may have a
      complementary role. Additional radionuclide techniques (e.g., gallium (67) or
      technetium (99) ) may have a role in complex cases. Given the life-threatening
      nature of cardiac involvement, prompt and aggressive treatment with
      corticosteroids or immunosuppressive agents, or both, is warranted. Long-term,
      possibly lifelong, therapy may be required. Serious, recurrent tachyarrhythmias
      may require implantation of an automatic cardioverter-defibrillator. Recognizing
      cardiac sarcoidosis and selecting a sensible management strategy remain the major
      obstacles facing clinicians.

PMID- 16088648
TI  - Hepatic, splenic, and gastrointestinal involvement with sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disease of unknown cause that
      primarily affects the lung and lymphatic systems of the body. However, any organ
      may be affected, including the abdominal organs and gastrointestinal tract. As
      with other forms of sarcoidosis, abdominal sarcoidosis presents diagnostic,
      prognostic, and therapeutic dilemmas. This article reviews the various forms of
      abdominal sarcoidosis, with particular attention given to methods of diagnosis
      and treatment options.

PMID- 16088649
TI  - Ocular manifestations of sarcoidosis.
AB  - Ophthalmic involvement in sarcoidosis may cause significant sight-threatening
      illness for patients. Studies of patients with histologically proven sarcoidosis
      have found 25 to 50% of patients to have ocular manifestations. The frequency in
      which eye disease is seen and the course that it takes vary with age, race, and
      geography. This article discusses relevant aspects of the ocular manifestations
      of sarcoidosis for the internist and pulmonologist. Overall disease presentation,
      specific types of ocular involvement, evaluation strategies, and treatment
      considerations are discussed.

PMID- 16088650
TI  - Sinonasal sarcoidosis: diagnosis and management.
AB  - Sinonasal sarcoidosis is a fairly uncommon, yet clinically challenging,
      manifestation of this systemic disease. The diagnosis is often difficult to
      establish, treatment options are often unclear, and ultimate clinical responses
      can be quite variable. This article discusses the varied clinical presentations
      of this unusual nasal inflammatory process, as well as various treatment options,
      from simple local nasal hygiene measures to more aggressive systemic therapy.
      Although the role of surgical intervention is controversial, a simple review of
      some of the indications for surgery in these patients helps to clarify this
      somewhat cloudy clinical area. Aggressive clinical management in conjunction with
      long-term surveillance can often produce dramatic clinical responses for these
      difficult patients with sarcoidosis in the sinonasal area.

PMID- 16088651
TI  - Sarcoidosis involving the musculoskeletal system.
AB  - Although sarcoidosis can affect virtually any organ, musculoskeletal involvement
      is infrequent. Early in the course of the disease, acute polyarthritis may be
      observed in up to 40% of patients, but this is often self-limited. Chronic or
      recurrent sarcoid arthritis is rare, affecting only 1 to 4% of patients.
      Asymptomatic involvement of muscles has been reported in 25 to 75% of patients in
      small series, but symptomatic involvement of muscles is rare. Although
      prospective studies assessing the prevalence of muscle involvement in sarcoidosis
      have not been done, several large retrospective studies suggest that symptomatic
      muscle involvement occurs in < 0.5% of patients with sarcoidosis. Patterns of
      sarcoid muscle involvement include chronic, progressive myopathy; nodular or
      tumorous sarcoidosis affecting muscles; and an acute polymyositis-like syndrome.
      Corticosteroid therapy is usually efficacious for the acute myositis variant but
      is less consistently helpful in the other forms (e.g., chronic myopathy or
      nodules). Similarly, clinically significant involvement of bone is rare (< 2-5%),
      and is often associated with chronic multisystemic disease, lupus pernio, and
      chronic uveitis. Unfortunately, osseous sarcoidosis is often unresponsive to
      therapy. In this review, we discuss the prevalence, clinical features, and
      management of sarcoidosis involving muscle, joints, and bones.

PMID- 16088652
TI  - Cutaneous sarcoidosis.
AB  - Sarcoidosis, a multisystem disease of unknown etiology, remains enigmatic in
      modern medicine. Skin involvement happens in < 20% of patients with this disease.
      Yet, when it occurs, it can be virtually diagnostic or it can be so baffling and
      obtuse as to test the diagnostic skills of virtually any clinical dermatologist.
      Clinically, sarcoidosis can mimic many conditions, in a manner similar to
      syphilis. Therefore, the astute clinician must always consider cutaneous
      sarcoidosis in diagnosing both obscure and ;;obvious'' diseases, such as
      folliculitis.

PMID- 16088653
TI  - Sarcoidosis of the thyroid and kidneys and calcium metabolism.
AB  - In sarcoidosis, the thyroid and the kidneys are infrequently affected. Clinically
      recognizable thyroid involvement occurs in < 1% of sarcoidosis patients.
      Hyperthyroidism, myxodema, and thyroid occur with an equal frequency. It is
      important to distinguish sarcoidosis of the thyroid from other infections and
      disorders of the gland. Renal involvement may present as granulomatous
      infiltration of the renal parenchyma, glomerulonephritis, renal arteritis, and
      nephrocalcinosis or renal stones. The latter are due to abnormalities of calcium
      metabolism. Hypercalcemia occurs in about 10 to 13% of sarcoidosis patients;
      hypercalciuria is three times more frequent. Calcium abnormalities may precede,
      follow, or occur at any time during the course of sarcoidosis. An endogenous
      overproduction of 1,25-dihydroxyvitamin D [1,25-(OH (2))-D (3)] by granulomatous
      tissue and activated macrophages results in an increase of intestinal absorption
      of calcium. Corticosteriods, chloroquine, and hydroxychloroquine subdue 1,25-(OH
      (2))-D (3) production and correct hypercalcemia and hypercalciuria.

PMID- 16088654
TI  - Therapy for extrapulmonary sarcoidosis.
AB  - The treatment of extrapulmonary sarcoidosis has to be adapted to the various
      organs involved. No treatment is necessary for most asymptomatic individuals. In
      some cases, topical therapy is sufficient to control problems, especially skin
      and eye involvement. Systemic therapy usually starts with corticosteroids.
      However, for chronic forms of the disease, steroid sparing alternatives such as
      methotrexate and hydroxychloroquine are useful. In some neurologic and cardiac
      cases, the response to corticosteroids is limited. In that case, alternatives are
      sought for these refractory patients. Drugs that inhibit tumor necrosis factor
      may prove useful in these patients. Among the new anti-tumor necrosis factor
      drugs are thalidomide and infliximab, an antibody to tumor necrosis factor.

PMID- 16088655
TI  - Case report: peritoneal sarcoidosis in an unusual location.
AB  - A 48-year-old woman underwent surgery for a lesion seen on ultrasound and
      interpreted as a uterine myoma. The surgery revealed multiple nodules that had
      seeded on the omentum, peritoneum, and ovaries. The macroscopic interpretation
      was either metastasis or tuberculosis. The biopsy showed noncaseating granulomas,
      and a diagnosis of peritoneal sarcoidosis was reported. The AFB (acid fast
      bacillus) and Lowenstein-Jensen culture were negative. She was treated with
      methylprednisolone for 1 year for pulmonary sarcoidosis progression, with a
      resulting decrease in her DLCO (diffusing lung capacity for carbon monoxide).
      Computed tomography showed only a slight decrease in the multiple nodules and
      cysts. She is currently symptom-free.

PMID- 16088656
TI  - Management of cerebral perfusion pressure.
AB  - The management of cerebral perfusion pressure is among the most controversial
      treatment issues. Cerebral perfusion pressure (CPP) is normally expressed as the
      difference between mean arterial blood pressure and intracranial pressure and has
      two important physiological roles in the patient with severe head injury. First,
      CPP represents the pressure gradient acting across the cerebrovascular bed and
      hence is an important factor in the regulation of cerebral blood flow. Second,
      CPP contributes to the hydrostatic pressure within the intracerebral vessels, and
      therefore is one of the factors that determines edema formation in the injured
      brain. The border between adequate and inadequate CPP should be assessed
      individually and continuously, as it may fluctuate in time. The treatment plan
      that includes rapid identification of intracranial hemorrhage, rapid evacuation
      of extra-axial blood, treatment of intracranial hypertension, and promotion of
      cerebral and systemic perfusion is likely to provide the best outcome for all
      patients.

PMID- 16088657
TI  - Smoke inhalation injury.
AB  - Smoke inhalation injuries are the leading cause of fatalities from burn injury.
      The major forms of inhalation injuries are carbon monoxide toxicity, injury to
      the upper airway, and pulmonary parenchymal damage. The compromised airway is
      protected by tracheal intubation, and respiratory failure is treated with
      assisted ventilation. Maintenance of good pulmonary hygiene, optomized fluid
      resuscitation, and routine invasive hemodynamic monitoring are the mainstays of
      therapy. The development of acute pulmonary insufficiency, pulmonary edema, or
      bronchopneumonia requires a comprehensive approach to all aspects of the illness.
      Acute pathophysiologic responses to inhalation injury are complex. Future
      therapies will target improved ventilatory strategies and the redundant host
      inflammatory response.

PMID- 16088658
TI  - Management issues in toxicology.
AB  - The lack of evidence-based information in toxicology results in debate and
      differing recommendations on management issues. Gastric lavage is often utilized
      to remove toxins from the stomach but a clinical benefit of the procedure has not
      been definitively demonstrated. A selective approach is warranted in each
      patient, and gastric lavage can be considered in patients with life-threatening
      ingestions if it can be performed within 60 minutes of ingestion. Whole bowel
      irrigation is a method of GI decontamination utilizing isotonic electrolyte
      solution. Although safe, there is currently insufficient data to establish
      definite indications for use. This technique can be considered for potentially
      toxic ingestions of lithium, iron, and sustained-release or enteric-coated drugs.
      Multiple-dose activated charcoal has been used to enhance elimination of drugs
      already absorbed into the body but the optimum dose and frequency of
      administration is not established. Based on volunteer studies and limited
      clinical reports, multiple-dose activated charcoal may be considered in patients
      with life-threatening ingestions of carbamazepine, dapsone, phenobarbital,
      quinine, or theophylline. A variety of interventions in addition to hemodialysis
      have been proposed to enhance lithium elimination. Forced saline diuresis and
      diuretics are not indicated. Although studies suggest that sodium polystyrene
      sulfonate may enhance elimination of lithium, no beneficial effects on clinical
      outcomes have been demonstrated and potential complications include hypokalemia
      and hypernatremia. Blood alkalinization for cyclic antidepressant toxicity has
      become standard therapy. Alkalinization is most effective in treating significant
      cardiac toxicity. Sodium bicarbonate, rather than hyperventilation, should be
      used initially to alkalinize blood. The benefit of blood alkalinization in the
      treatment of hypotension and seizures is not established.

PMID- 16088659
TI  - Nutritional support in acute pancreatitis: an update on management issues.
AB  - About 20% of acute pancreatitis cases develop necrosis and have a high risk of
      inflammatory and infectious complications and a high mortality rate. Acute
      pancreatitis has a variety of causes and despite years of research its
      pathogenesis remains complex and obscure. Both local and systemic inflammatory
      responses play key roles in the pathophysiology of this disorder. Treatment plans
      continue to rely on supportive care without proven specific therapies. Pancreatic
      rest and use of total parenteral nutrition (TPN) were the gold standard for
      nutritional support of these challenging patients. Because numerous studies in
      other critically ill patients demonstrated benefits of enteral nutrition, recent
      investigations compared TPN to enteral nutrition in acute pancreatitis. These
      studies indicated that enteral nutrition delivered into the jejunum was tolerated
      well, even in patients with severe acute pancreatitis. "Mild'' cases of
      pancreatitis should improve and tolerate oral nutrition within a few days. In
      contrast, "severe'' cases of pancreatitis or those with a protracted clinical
      course require nutritional support to aid in preventing adverse effects of
      starvation and nutrient deficiencies. Current recommendations are to attempt
      enteral nutrition in patients with acute pancreatitis prior to instituting TPN.
      Further studies to determine optimal nutrient composition are warranted and
      should investigate the possibility of modulating the inflammatory response
      induced by pancreatitis to improve outcomes.

PMID- 16088660
TI  - Selected controversies in cardiopulmonary resuscitation.
AB  - Cardiopulmonary resuscitation (CPR) is performed frequently by paramedics,
      emergency department personnel, and inpatient physicians. Unfortunately, after
      more than 40 years of practice and study, there are still many controversies and
      unresolved treatment issues. This article focuses on four current controversies
      in CPR: (1) the role of end-tidal CO2 (ETCO2) detection, (2) the use of
      bicarbonate, (3) whether epinephrine is the optimal alpha agonist, and (4)
      whether amiodarone should replace lidocaine as the initial antiarrhythmic of
      choice in the treatment of ventricular fibrillation.

PMID- 16088661
TI  - Controversies in the antibiotic management of critically ill patients.
AB  - Preventing infection, managing antibiotics, and controlling antibiotic resistance
      are integral to the daily practice of any physician caring for critically ill
      patients. Many controversies remain in this area, but improving our ability to
      manage anti-infective drugs is likely to be a determinant factor on the outcome
      of critically ill patients. Several measures to prevent nosocomial infections are
      available, including selective digestive decontamination (SDD) and antibiotic
      coated catheters, but a careful assessment of the effect of these strategies upon
      resistance is needed before considering their extensive use in the ICU.
      Antibiotic therapy of severely infected patients can be considered as a two-step
      contract, the first part of which consists in providing individual patients with
      the best antibiotic strategy. This raises important, although often unsolved,
      questions regarding the dose, the interest of combining two antibiotics, and the
      length of therapy. The second part of the contract concerns not only individual
      patients but the community. Reassessment of the initial therapy is mandatory to
      avoid prolonged and unnecessary usage of broad spectrum and costly antibiotics,
      which increase resistance pressure. In many cases, antibiotics can be either
      stopped or changed after 2 or 3 days.

PMID- 16088662
TI  - Inotrope/vasopressor support in sepsis-induced organ hypoperfusion.
AB  - Vasoactive agents are commonly required in the management of septic shock not
      only to restore a sufficient tissue perfusion pressure but also to increase blood
      flow and oxygen delivery to the organs. Importantly, vasoactive agents are no
      substitute for fluid therapy. Defining end points for therapy remains difficult.
      These should be, above all, clinical. Even though the gut may play an important
      role in the development of multiple organ failure, the use of gastric tonometry
      to guide therapy cannot be recommended at this time. Study of the
      microcirculation at the bedside with orthogonal polarization spectral imaging may
      be helpful in the future. Adrenergic agents are the preferred agents for
      hemodynamic stabilization. Dopamine and norepinephrine are the drugs of choice to
      increase arterial pressure. Dobutamine remains the agent of choice to increase
      blood flow to the organs, including the gut and the kidneys. Many questions
      remain unanswered with respect to optimal hemodynamic management of septic shock.

PMID- 16088663
TI  - Acute myocardial ischemia and infarction: making the right decisions in
      antithrombotic and reperfusion therapies.
AB  - Acute coronary syndromes, which include unstable angina and myocardial infarction
      (MI), have the common pathophysiological mechanism of intracoronary thrombus
      formation. Treatment of an acute MI initially focuses on reperfusion with
      thrombolysis or percutaneous coronary interventions (PCI)s. Primary or direct
      percutaneous interventions, with traditional angioplasty and stenting, appear to
      provide superior efficacy for acute MI, although temporal factors are crucial.
      However, antiplatelet and antithrombin therapies are also vital for the
      maintenance and enhancement of complete coronary perfusion and for primary
      management of non-Q wave myocardial infarction (NQWMI) and unstable angina.
      Recent advances in the pharmacological treatment include the use of direct
      thrombin inhibitors, low-molecular-weight heparin, and glycoprotein IIb/IIIa
      antagonists, all of which have shown substantial benefit for acute coronary
      syndromes. The article focuses on the clinical literature supporting the utility
      of recent therapeutic advances and outlines the current indications for such
      treatments.

PMID- 16088664
TI  - Nonphysician clinicians in the ICU.
AB  - Until very recently the medical care of the patient in the intensive care unit
      (ICU) was provided primarily by physicians. Many of these physicians were
      specifically trained as intensivists to manage the critically ill and provide
      minute to minute titration of care to improve the outcomes of these patients.
      However there has been a change in the delivery of critical care in many centers
      with the addition of NPCs (nonphysician clinicians) to the team. A 1998 article
      in JAMA listed 10 nonphysician disciplines that will affect the demand for
      physicians in the future; this article focuses on only two of these disciplines:
      physician assistants (PAs) and acute care nurse practitioners (ACNPs). A driving
      force for the addition of these NPCs to the ICU team is the downsizing of
      resident programs. This article explores the utilization of NPCs in the ICU,
      including the perceived advantages and potential controversies associated with
      these practitioners.

PMID- 16088665
TI  - Models of critical care delivery: physician staffing in the ICU.
AB  - Although a consensus has emerged over the value of intensive care units (ICUs) in
      improving both the outcome and efficiency of critical care, the optimal staffing
      configuration of physicians who provide this care remains controversial. The
      value of open ICUs, where many clinicians can admit and care for patients, versus
      closed ICUs, where an on-site intensivist or housestaff team (or both) provides
      primary care of the critically ill patient is one aspect of this controversy. The
      roles of the intensivist, the ICU housestaff team, and the ICU director have also
      been debated. This article reviews the available literature on physician staffing
      in critical care units and its relationship to outcome and cost-effectiveness of
      care.

PMID- 16088666
TI  - Comfort and distress in the ICU: scope of the problem.

PMID- 16088667
TI  - Delirium in the intensive care unit: an under-recognized syndrome of organ
      dysfunction.
AB  - The intensivist should think of delirium, or acute central nervous system
      dysfunction, as the brain's form of "organ dysfunction.'' Delirium is extremely
      common in intensive care unit (ICU) patients due to factors such as comorbidity,
      critical illness, and iatrogenesis. This complication of hospital stay is
      extremely hazardous in older persons and is associated with prolonged hospital
      stays, institutionalization, and death. Neurologic dysfunction compromises
      patients' ability to be removed from mechanical ventilation or achieve full
      recovery and independence. Yet ICU nurses and physicians are usually unaware of
      the presence of hypoactive delirium and only recognize this disturbance in
      agitated patients (hyperactive delirium). More importantly, there are few studies
      that have included ICU patients in the assessment or prevention of delirium. This
      article reviews the definition and salient features of delirium, its primary risk
      factors, a newly validated instrument for delirium assessment that is being
      developed for ICU nurses and physicians, and pharmacological agents associated
      with the development of delirium and used in its management.

PMID- 16088668
TI  - Pain in the intensive care unit: recognition, measurement, management.
AB  - There has been a resurgence in interest in the in-hospital management of pain,
      largely related to results of investigations into the role of analgesia in
      outcome and cost-efficiency. The traditional aim of analgesia as simply an
      altruistic goal has been supplanted by the goal of impacting on the altered
      physiology accompanying critical illness and trauma. Elucidation of the effect of
      pain and the accompanying stress response on pulmonary dysfunction in particular,
      but also on myocardial ischemia and coagulation, has suggested that the provision
      of adequate analgesia by time-honored methods may not in itself effect a
      reduction in morbidity without attention to the method of analgesic delivery and
      choice of agent.

PMID- 16088669
TI  - Optimizing patient-ventilator synchrony.
AB  - Mechanical ventilation assumes the work of breathing, improves gas exchange, and
      unloads the respiratory muscles, all of which require good synchronization
      between the patient and the ventilator. Causes for patient-ventilator
      dyssynchrony include both patient factors (abnormalities of respiratory drive and
      abnormal respiratory mechanics) and ventilator factors (triggering, flow
      delivery, breath termination criteria, the level and mode of ventilator support,
      and imposed work of breathing). Although patient-ventilator dyssynchrony can
      often be detected on physical exam, careful analysis of ventilator waveforms
      (pressure-time, flow-time) allows for more precise definition of the underlying
      cause. Patient-ventilator interaction can be improved by reversing patient
      factors that alter respiratory drive or elevate patient ventilatory requirements
      and by correcting factors that contribute to dynamic hyperinflation. Proper
      setting of the ventilator using sensitive triggering mechanisms, satisfactory
      flow rates, adequate delivered minute ventilation, matching machine T(I) to
      neural T(I), and applying modes that overcome the imposed work of breathing,
      further optimize patient-ventilator synchrony.

PMID- 16088670
TI  - Sleep in the critically ill patient.
AB  - The sleep of intensive care unit (ICU) patients is remarkably disrupted. Several
      studies, employing both subjective and objective measures of sleep quality, have
      demonstrated that critically ill patients exhibit severe sleep fragmentation and
      reduced restorative sleep, particularly a suppression of rapid eye movement (REM)
      sleep. The cause of sleep disruption in the ICU appears to be multifactorial and
      includes both the patients' acute and chronic illnesses and factors that are
      unique to the ICU environment. Noise has been a significant focus of
      investigation, and the effects of medications, light, and patient-care activities
      have also been examined. Several questions remain to be answered so that
      caregivers can improve sleep in ICU patients, including the relative contribution
      of different sleep-disrupting factors and possible changes in patient
      susceptibility to these factors over time.

PMID- 16088671
TI  - Use of sedative medications in the intensive care unit.
AB  - Current choices for sustained sedation in the critically ill include the
      benzodiazepines, the opiates, and propofol. Each of these groups of medications
      has their particular benefits: benzodiazepines provide the greatest amnesia,
      opiates are the only agents to provide analgesia, and propofol is the most easily
      titratable and the least likely to excessively accrue. The literature seems to
      favor propofol over the benzodiazepines as the most cost-effective solution to
      sustained sedation. A newly approved agent, dexmedetomidine, holds promise as a
      continuous infusion that can provide both anxiolysis and analgesia, but without
      the ventilatory depression seen in the other classes of sedatives. Further
      research is needed to determine the role of dexmedetomidine in the ICU. The
      emerging standard of care for sustained sedation is the use of standardized
      protocols, formulated with the help of clinical practice guidelines, and titrated
      with the guidance of sedation monitoring.

PMID- 16088672
TI  - Neuromuscular blockade in the intensive care unit.
AB  - Neuromuscular blocking agents (NMBA) are frequently utilized in the ICU,
      primarily to facilitate mechanical ventilation. An ideal NMBA is nondepolarizing,
      has no propensity to accumulate, is easily titrated, has a rapid onset and
      offset, does not rely on organ function for metabolism, and has no toxic or
      active metabolites. Current NMBAs are classified as aminosteroids or
      benzylisoquinoliniums and have different features, but none are ideal. Selection
      of the best NMBA is determined by individual patient characteristics. Proper use
      of these agents includes a comprehensive plan to manage all aspects of care
      affected by NMBA, as well as monitoring of clinical effect and degree of
      neuromuscular blockade via periodic peripheral nerve stimulation. There are well
      recognized complications of NMBA, including prolonged drug effect and acute
      quadriplegic myopathy. The latter condition can result in prolonged
      rehabilitation. The use of an NMBA can be essential for the successful outcome
      from critical illness; however, cautious use of these agents with a structured
      approach to minimize complications is urged.

PMID- 16088673
TI  - Monitoring sedation, agitation, analgesia, neuromuscular blockade, and delirium
      in adult ICU patients.
AB  - Preliminary evidence suggests that closely monitoring sedation may have a
      positive effect on patient outcomes, including reductions in intensive care unit
      (ICU) stay, duration of mechanical ventilatory support, and number of diagnostic
      tests requested to assess central nervous system function. In the last few years,
      subjective instruments to assess agitation and sedation have been developed and
      tested for reliability and validity, including the Sedation-Agitation Scale and
      the Motor Activity Assessment Scale. Similar efforts directed to delirium among
      ICU patients have produced several assessment tools to help clinicians with this
      difficult area of patient care. Promising techniques for objective assessment of
      sedation (such as the bispectral index) and strategies to guide neuromuscular
      blockade with train-of-four (TOF) or clinical exam monitoring have emerged.
      Future efforts should focus on evaluating the impact of these monitoring
      techniques on specific outcomes in an effort to improve patient comfort, minimize
      adverse events, and reduce resource consumption.

PMID- 16088674
TI  - Cost considerations in sedation, analgesia, and neuromuscular blockade in the
      intensive care unit.
AB  - Sedation of critically ill patients is a costly endeavor. Costs of commonly used
      intensive care unit (ICU) sedatives range from pennies to more than $500 per day.
      Although the agents account for some of this expense, complications related to
      the use of these drugs in the ICU produce even greater costs. Prolongation of
      mechanical ventilation and length of stay are some of the common complications
      resulting from non-ideal use of these drugs. Sedative agents also impair
      neurological evaluation in many critically ill patients, which may mask detection
      of acute delirium resulting from intercurrent illness or intracranial
      catastrophes and can lead to excessive diagnostic testing. Opiates may result in
      gastrointestinal dysfunction with resulting malnutrition and perhaps bacterial
      translocation and sepsis. Neuromuscular blocking agents may cause prolonged
      paralysis and disability in critically ill patients who receive them. Simple
      dosing strategies based on pharmacological principles may decrease the incidence
      of these costly problems.

PMID- 16088675
TI  - Multidisciplinary management of sedation and analgesia in critical care.
AB  - Management of sedation and analgesia in critical care medicine is a
      multidisciplinary process that involves physicians, nurses, pharmacists, and
      other healthcare providers. Optimal management of these common issues includes
      recognition of the importance of predisposing and causative conditions that
      contribute to the sensations of pain and discomfort, anxiety, and delirium.
      Treatment includes pharmacological intervention, correction of predisposing
      factors, and use of other preventative and nonpharmacological measures. It is
      increasingly clear that, although necessary for patient comfort, sedative and
      analgesic medications can have adverse consequences, including side-effects as
      well as prolonged mechanical ventilation and ICU length of stay. Optimal use of
      sedative and analgesic medications involves matching unique properties of
      specific medications with individual patient characteristics. Guidelines that
      minimize unnecessary variability in practice, prevent excessive medication, and
      emphasize management based on individual patient characteristics improve the
      effective utilization of these medications.

PMID- 16088676
TI  - Clinical epidemiology of acute lung injury.
AB  - Acute lung injury (ALI) remains a serious threat to critically ill patients and
      continues to pose challenges to clinicians and investigators as they strive to
      better identify and treat these patients. Over 30 years of clinical and basic
      science investigations have led to a better understanding of the pathophysiology,
      risk factors, and prognosis of this entity but we still lack a "gold standard''
      for its identification. The American-European Consensus Conference definition has
      helped in the effort to standardize the definition of ALI but is still fraught
      with difficulties in the application of criteria for the chest radiograph,
      hypoxemia, and left atrial hypertension. As further efforts are undertaken to
      better define ALI and to more accurately describe its incidence, it is critical
      that methodology to assess the accuracy and reliability of such definitions be
      utilized. This union of clinical epidemiology, clinical research, and basic
      science will not only better describe the population burden of ALI but will also
      better track the effect of current and future therapeutic interventions.

PMID- 16088677
TI  - Pathophysiology of acute lung injury.
AB  - The acute respiratory distress syndrome (ARDS) is a life-threatening syndrome
      that may occur in any patient without any predisposition and that is mostly
      triggered by underlying processes such as sepsis, pneumonia, trauma, multiple
      transfusions, and pancreatitis. ARDS is defined by (1) acute onset, (2) bilateral
      infiltrates in chest x-rays, (3) absence of left ventricular failure, and (4)
      severe arterial hypoxemia with a PaO2/FiO2 ratio less than 200 mmHg. Still, ARDS
      is feared (mortality 30-40%) and relatively frequent (incidence between 13.5 per
      100,000 to 75 per 100,000). Acute lung injury (ALI) describes a similar, but less
      severe, clinical condition, with PaO2/FiO2 values between 200 and 300 mmHg.
      Despite ongoing and intensive scientific research in this area, the mechanisms
      underlying ALI/ARDS are still not completely understood, and until recently,
      there were no studies demonstrating any beneficial effect of a single treatment
      modality in ARDS. The recent report that a specific approach to ventilatory
      support can significantly reduce mortality in ARDS underscores the need for
      better understanding of the pathophysiological events occurring in this syndrome.
      This review therefore summarizes the current pathophysiological concepts
      underlying the evolution of acute hypoxemic respiratory failure and focuses on:
      (1) possible reasons for the development of ALI/ARDS; (2) cellular and humoral
      mediator responses leading to a sustained and self-perpetuating inflammation of
      the lung; (3) consequences with regard to fluid balance, pulmonary perfusion,
      ventilation, and efficiency of gas exchange; and (4) mechanisms underlying the
      aggravating complications commonly seen in ARDS, especially ventilator-associated
      lung injury, ventilator-associated pneumonia, and lung fibrosis.

PMID- 16088678
TI  - Pulmonary and extrapulmonary forms of acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is usually viewed as the functional
      and morphological expression of a similar underlying lung injury caused by a
      variety of insults. However, the distinction between ARDS due to a direct (ARDSp)
      versus an indirect (ARDSexp) lung injury is gaining more attention as a means of
      better comprehending the pathophysiology of ARDS and for modifying ventilatory
      management. From the few published studies, we can summarize that: (1) the
      prevalent damage in early stages of a direct insult is intra-alveolar, whereas in
      indirect injury it is the interstitial edema. It is possible that the two insults
      may coexist (i.e., one lung with direct injury (as in pneumonia) and the other
      with indirect injury, through mediator release from the contralateral pneumonia);
      (2) the radiological pattern, by chest x-ray or computed tomography (CT), is
      different in ARDSp (characterized by prominent consolidation) and ARDSexp
      (characterized by prominent ground-glass opacification); (3) in ARDSp lung
      elastance is more markedly increased than in ARDSexp, where the main abnormality
      is the increase in chest wall elastance, due to abnormally high intra-abdominal
      pressure; (4) positive end-expiratory pressure (PEEP), inspiratory recruitment,
      and prone position are more effective to improve respiratory mechanics, alveolar
      recruitment, and gas-exchange in ARDSexp. Further studies are warranted to better
      define if the distinction between ARDS of different origins can improve clinical
      management and survival.

PMID- 16088679
TI  - Ventilator-induced lung injury and recommendations for mechanical ventilation of
      patients with ARDS.
AB  - Mechanical ventilation is life sustaining and is the standard therapy for acute
      respiratory failure. The 16th century anatomist Vesalius is often credited for
      the earliest account of positive-pressure ventilation. In his work De humani
      corporis fabrica (On the Fabric of the Human Body), he described how an animal
      could be resuscitated by blowing into a reed inserted into a hole in its trachea.
      Although positive pressure ventilation using bellows was first used for drowning
      victims in the 1700s, there were soon concerns that such therapy could in fact be
      harmful to the lungs. In 1827, Leroy d'Etoille condemned bellows ventilation
      after discovering that it could lead to emphysema and tension pneumothoraces.
      Subsequently, positive pressure ventilation would be virtually abandoned for over
      100 years. Despite this early concern about the potential for harm from
      mechanical ventilation, it is only in the last one to two decades that research
      into so-called ventilator-induced lung injury (VILI) has blossomed. Indeed,
      although initial studies have focused on which ventilatory parameters are
      associated with the most (or least) harm, there has been an explosion of research
      in the last 5 years attempting to delineate the basic cellular mechanisms by
      which mechanical ventilation injures the lung. Recently, there has been exciting
      evidence to suggest that lung injury induced by mechanical ventilation may have
      important systemic consequences, including multi-organ dysfunction. Lastly and
      most importantly, there is accumulating data from clinical trials in humans that
      ventilatory strategies designed to avoid VILI can in fact save lives.

PMID- 16088680
TI  - Acute respiratory distress syndrome: adjuncts to lung-protective ventilation.
AB  - Despite recent advances in understanding, the management of acute respiratory
      distress syndrome (ARDS) remains a challenging clinical problem. Optimization of
      gas exchange and preventing the iatrogenic propagation of lung injury are
      cornerstones of its clinical management. A number of novel approaches and
      adjuncts to mechanical ventilation have been described over the past decade to
      help achieve these goals, and some have been widely implemented with varying
      degrees of success. This chapter will review the rationale and evidence
      supporting the use of such adjunctive strategies.

PMID- 16088681
TI  - Acute respiratory distress syndrome: innovative therapies.
AB  - Since its description in 1967, the acute respiratory distress syndrome (ARDS) has
      become one of the most studied pathophysiological processes in intensive care
      units worldwide. The current state of knowledge about this severe illness and its
      associated mediators has come from the study of relevant animal models. In the
      mid-1970s, the development of the sheep model of ARDS and later, the porcine
      model, led to the discovery of a wide variety of inflammatory lipid mediators,
      cytokines, and proteases, to name but a few. Recognition of the presence of such
      highly toxic mediators associated with the development of ARDS has led to
      numerous potential targets for drug development toward therapeutic intervention.
      Through implementation of a standardized definition for ARDS and its less severe
      sibling acute lung injury (ALI), growth in patient-oriented research has been
      possible. Substantial numbers of new therapies have been brought forth and
      examined in recent years, many of which remain controversial. This article is a
      critical appraisal of the potential therapeutic options investigated in recent
      years for the management of ALI/ARDS.

PMID- 16088682
TI  - Cardiovascular management of ARDS.
AB  - The acute respiratory distress syndrome (ARDS) is often thought of as a pulmonary
      disease yet death most often occurs due to multiple system organ failure (MSOF).
      The cardiovascular system plays a key role in the evolution of multiple organ
      involvement and is, itself, a frequently involved organ system.

PMID- 16088683
TI  - Ventilator-associated pneumonia complicating the acute respiratory distress
      syndrome.
AB  - Pulmonary infections span a wide spectrum, ranging from self-limited processes
      (e.g., tracheobronchitis) to life-threatening infections including both community
      acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). Together,
      pneumonia and influenza rank as the sixth leading cause of death in the United
      States and lead all other infectious diseases in this respect. Pneumonia is the
      second-most-common hospital-acquired infection in the United States, accounting
      for 17.8% of all hospital-acquired infections and 40,000 to 70,000 deaths per
      year. HAP is the most common nosocomial infection occurring in patients requiring
      mechanical ventilation, developing in 6.5% of patients after 10 days and in 28%
      of patients after 30 days of ventilatory support. Patients acquiring HAP have a
      greater risk of mortality than comparably ill ventilated patients who do not
      develop pneumonia. Ventilator-associated pneumonia (VAP) specifically refers to a
      bacterial pneumonia developing in patients with acute respiratory failure who
      have been receiving mechanical ventilation for at least 48 hours. The etiologic
      bacteriologic agents associated with VAP typically differ based on the timing of
      the occurrence of the infection relative to the start of mechanical ventilation.
      VAP occurring within 96 hours of the onset of mechanical ventilation is usually
      due to antibiotic-sensitive bacteria that colonize the patient prior to hospital
      admission (e.g., Streptococcus pneumoniae, Haemophilus influenza, oxacillin
      sensitive Staphylococcus aureus). VAP developing after 96 hours of ventilatory
      support is more often associated with antibiotic-resistant bacteria including
      oxacillin-resistant Staphylococcus aureus, Acinetobacter species and Pseudomonas
      aeruginosa. However, more recent data suggest that hospitalization and exposure
      to antibiotics prior to the start of mechanical ventilation are important risk
      factors for the occurrence of VAP attributed to antibiotic-resistant bacteria.
      Therefore, these risk factors should be considered when deciding on an
      appropriate empiric antibiotic regimen regardless of the onset of VAP. VAP and
      catheter-associated bloodstream infections are the leading causes of infection
      acquired in the intensive care unit (ICU) setting. Patients in the ICU have rates
      of HAP that are as much as five to ten times higher than the rates in general
      hospital wards. Additionally, like nosocomial bloodstream infections, VAP is
      associated with an attributable mortality beyond that accounted for by patients'
      severity of illness. The attributable mortality associated with VAP appears to be
      greatest for "high-risk'' antibiotic-resistant bacteria including Pseudomonas
      aeruginosa and oxacillin-resistant Staphylococcus aureus. The greater hospital
      mortality associated with these "high-risk'' pathogens has been attributed to the
      virulence of these bacteria and the increased occurrence of inadequate initial
      antibiotic treatment of VAP due to the presence of antibiotic resistance. This
      review provides an overview of the clinical importance of VAP. We then describe
      how this nosocomial infection influences the management and outcomes of patients
      with the acute respiratory distress syndrome (ARDS).

PMID- 16088684
TI  - Long-term outcomes after ARDS.
AB  - Early reports of late outcomes among survivors of ARDS indicated that most
      patients improved dramatically after their intensive care unit stay, and few
      lived with residua of their once-severe pulmonary injury. Over the last decade, a
      collection of new studies with improved methodology and novel questions has
      improved our understanding of life after ARDS. After reviewing these newer
      investigations in the context of previously published literature, we have drawn
      several preliminary conclusions: (1) Long-term survival after hospital discharge
      is unaffected by ARDS, but is strongly affected by ARDS risk factor and
      comorbidities. (2) Respiratory symptoms after ARDS are more prevalent than
      previously indicated, but improve over the first 12 months of recovery. (3)
      Pulmonary function testing reveals marked impairment soon after ARDS. There is
      improvement over the first 6 months, with lingering mild decreases in lung volume
      and diffusing capacity in most patients. A small group of patients have severe
      impairment without improvement. (4) Quality of life, functional independence, and
      cognitive function are severely affected by ARDS, with dramatic improvement over
      the first year. Quality of life is lower than in matched critically ill controls.
      (5) Significant numbers of ARDS survivors suffer from posttraumatic stress
      syndrome. This is an exciting time for research in long-term outcomes of ARDS,
      with potential for future studies that validate these single-center hypotheses,
      explore their ramifications, and investigate the impacts of changing practices in
      the intensive care unit in the acute phase of ARDS.

PMID- 16088685
TI  - The clinical significance of histopathologic subgroups in idiopathic interstitial
      pneumonia: is surgical lung biopsy essential?
AB  - For many years, the clinical entity of idiopathic interstitial pneumonia (IIP)
      has been a source of confusion for physicians. There has been much debate over
      the utility of subclassifying this condition histopathologically. It now appears
      that such classification is useful, and the most important distinction is the
      presence or absence of usual interstitial pneumonia (UIP). Unlike the other
      histopathologic subgroups, UIP has a grave prognosis and responds poorly to
      traditional therapies. To emphasize this clinical difference, the diagnosis of
      idiopathic pulmonary fibrosis (IPF), once used synonymously with IIP, is now
      reserved for only those patients with the histopathologic pattern of UIP.
      Although the gold standard for the diagnosis of IPF/UIP remains surgical lung
      biopsy, recent studies suggest that careful clinical and radiographic evaluation
      can identify IPF/UIP with a specificity of 90% or more. In the absence of a clear
      clinical diagnosis, we recommend pursuing surgical lung biopsy. Knowledge of the
      underlying histopathology will allow for more accurate prognosis, help guide
      therapy, and make possible the clinical investigation of novel therapeutic agents
      for patients with IIP.

PMID- 16088686
TI  - Usual interstitial pneumonia.
AB  - Usual interstitial pneumonia (UIP) is a distinct histological lesion observed in
      idiopathic pulmonary fibrosis (IPF), but can be found in other etiologies. The
      diagnosis of UIP can be established by surgical lung biopsy or by high resolution
      thin section computed tomographic scans (provided the radiographic features are
      classical). Historically, patients labeled as "IPF'' encompassed a group of
      disorders including UIP as well as other idiopathic interstitial pneumonias,
      which differ from UIP in prognosis and responsiveness to therapy. Current
      recommendations from international consensus statements restrict the term IPF to
      patients with idiopathic UIP. The inciting cause(s) and pathogenesis of UIP have
      not been elucidated, but alveolar epithelial cell injury and dysregulation or
      altered phenotypic expression of fibroblasts are key elements. Inflammatory cells
      may play minor roles in initiating or propagating the fibrotic process. The
      prognosis of UIP is poor. Mean survival following diagnosis approximates 3 years.
      Current therapies are of unproven value. Corticosteroids or immunosuppressive
      agents have been most often used, but data affirming benefit are lacking. Single
      lung transplantation is a viable option for patients failing medical therapy.
      Novel therapeutic strategies based upon inhibiting fibroproliferation or
      enhancing alveolar reepithelialization are desperately needed. In this article,
      we discuss diagnostic criteria for UIP (both histopathological and radiographic),
      natural history and clinical course, and therapeutic approaches (both current and
      future).

PMID- 16088687
TI  - Desquamative interstitial pneumonia and respiratory bronchiolitis-associated
      interstitial lung disease.
AB  - Our understanding of the various types and patterns of diffuse lung disease that
      might result in fibrosis has evolved considerably over the last 50 years. Many
      entities now regarded as distinct had been previously "lumped'' together as a
      single disease, "lung fibrosis,'' and more recently misdiagnosed as idiopathic
      pulmonary fibrosis (IPF, synonymous with cryptogenic fibrosing alveolitis). In
      1965 desquamative interstitial pneumonia (DIP) was first described, and later it
      was clearly demonstrated that the clinical and pathological features of DIP and
      IPF were different, particularly in terms of survival and response to therapy.
      They are not part of the same disease spectrum nor does DIP evolve into usual
      interstitial pneumonia (UIP). Later, in the mid-1980s, RBILD was described as a
      distinct clinicopathologic syndrome with features consistent with an interstitial
      lung disease among current or former smokers. In the recent histopathological
      classification of idiopathic interstitial pneumonia (IIP), DIP and RBILD have
      been included as separate entities, although there is some evidence that suggests
      they may lie at the two ends of a single spectrum. The debate bears similarities
      with the debate about DIP and UIP and is as yet unresolved. This article will
      give a broad and current overview of these two rarer forms of IIP, including
      issues that relate to diagnosis, imaging, histopathology, treatment, and
      prognosis.

PMID- 16088688
TI  - Acute interstitial pneumonitis: current understanding regarding diagnosis,
      pathogenesis, and natural history.
AB  - Acute interstitial pneumonitis (AIP) is a fulminant disease culminating in acute
      respiratory failure and often death. Originally described in 1935 by the
      pathologists Hamman and Rich, this rare syndrome is characterized by rapidly
      progressive pulmonary fibrosis, leading to frequent confusion with idiopathic
      pulmonary fibrosis. In fact, the eponym Hamman-Rich syndrome became synonymous
      with idiopathic pulmonary fibrosis despite clear differences in clinical
      presentation, radiography, pathology, and survival. In 1986, Katzenstein
      described eight patients with acute respiratory failure of unknown etiology. On
      biopsy, organizing diffuse alveolar damage was present in all specimens. Given
      the idiopathic nature of the disease, Katzenstein coined the phrase acute
      interstitial pneumonitis to distinguish it from the fibroproliferative stage of
      the acute respiratory distress syndrome (ARDS), which has an identical pathology.
      Olson et al retrospectively examined Hamman and Rich's original cases, compared
      them to contemporary cases of AIP, and found the two identical. Since then,
      little progress into understanding this disease has been made. Many questions
      still linger regarding the epidemiology, pathogenesis, and outcome. We recently
      published our experience with AIP providing new information regarding natural
      history. This review summarizes the current literature on AIP emphasizing
      diagnostic criteria, pathogenesis, and natural history.

PMID- 16088689
TI  - Lymphocytic interstitial pneumonia and other lymphoproliferative disorders in the
      lung.
AB  - Lymphocytic interstitial pneumonia (LIP) is a clinicopathologic term that relates
      histologically to a dense interstitial infiltrate of mainly T cells, plasma
      cells, and histiocytes, with germinal centers often identified. Its precise
      etiology is unknown, but there are strong clinical associations with several
      autoimmune disorders, as well as both congenital and acquired immunodeficiency
      syndromes. It may overlap histologically with both extrinsic allergic alveolitis
      and nonspecific interstitial pneumonia, and therefore close clinical/radiological
      association is essential for diagnosis. LIP also overlaps clinically and
      histologically with follicular bronchitis/bronchiolitis, the latter showing
      reactive lymphoid hyperplasia with a peribronchiolar distribution predominantly
      comprising lymphoid follicles. LIP may also be histologically indistinguishable
      from nodular lymphoid hyperplasia and lymphomas arising from mucosa-associated
      lymphoid tissue (MALT) but can usually be differentiated via analysis of clinical
      and imaging data plus assessment of immunohistochemistry and gene rearrangement
      studies. Other entities include lymphomatoid granulomatosis, intravascular
      lymphomatosis, Castleman's disease, primary pleural lymphomas, primary effusion
      lymphomas, plasmacytomas, and secondary involvement by lymphoma, but these should
      all be readily distinguishable from lymphocytic interstitial pneumonia if all
      clinical, imaging, and histological data are apparent.

PMID- 16088690
TI  - Nonspecific interstitial pneumonia (NSIP).
AB  - Nonspecific interstitial pneumonia (NSIP) represents one histologic subtype of
      idiopathic interstitial pneumonia (IIP). NSIP is typified by temporal homogeneity
      and less profusion of fibroblastic foci than is seen with usual interstitial
      pneumonia (UIP), the most common IIP. Clinically patients with NSIP present with
      similar symptoms (cough and dyspnea) when compared to patients with UIP. The
      duration of these symptoms prior to presentation is variable. The finding of
      fever may be more common in NSIP and clubbing may be more common in UIP; however,
      both findings can be seen in either UIP or NSIP. Physiological findings typically
      demonstrate a restrictive ventilatory defect with decreased gas transfer; little
      difference exists between UIP and NSIP. High resolution computed tomography
      (HRCT) scans are more likely to show honeycombing with UIP and a ground-glass
      pattern with NSIP, however, either of these findings can be seen with UIP or
      NSIP. The most striking differential feature between NSIP and UIP is the markedly
      better prognosis for patients with NSIP, a finding that cannot be explained by
      baseline differences in physiology or radiographic features. In this article we
      explore the clinical, physiological, and radiographic features of NSIP. We also
      review available information regarding response to therapy and prognosis.

PMID- 16088691
TI  - Giant cell interstitial pneumonia (hard metal lung disease, cobalt lung).
AB  - Hard metal lung disease is a rare form of occupational lung disease that can
      occur in workers engaged in the manufacture, utilization, or maintenance of tools
      composed of hard metal [a material composed mainly of tungsten carbide (WC) and
      cobalt] or diamond-cobalt. Clinically, the condition resembles hypersensitivity
      pneumonitis, with subacute presentations and possible evolution to pulmonary
      fibrosis. However, this interstitial lung disease is uniquely characterized by
      the presence of bizarre ;;cannibalistic'' multinucleated giant cells in the
      alveoli and the bronchoalveolar lavage. A pathological diagnosis of giant cell
      interstitial pneumonitis (GIP) is, therefore, specific for hard metal lung
      disease, even though not all affected subjects exhibit this pathognomonic
      feature. Cobalt is the critical toxic component causing hard metal lung disease,
      hence also the term cobalt-lung. Hard metal lung disease is more likely to occur
      in poorly regulated workplaces, but its occurrence depends mainly on individual
      susceptibility, rather than on cumulative exposure, so that even young subjects
      may be affected.

PMID- 16088692
TI  - Cryptogenic organizing pneumonia.
AB  - The terms cryptogenic organizing pneumonia (COP) and idiopathic bronchiolitis
      obliterans with organizing pneumonia (BOOP) are synonymous. Typical COP should be
      viewed as a clinicopathological syndrome, consisting of respiratory and systemic
      symptoms (usually low-grade), patchy consolidation on chest radiography and
      computed tomography, a restrictive defect on pulmonary function testing, and the
      presence of buds of granulation tissue within the distal airways and alveolar
      spaces. In the correct clinical context, the diagnosis can be secured by
      transbronchial biopsy, with typical bronchoalveolar lavage features providing
      useful diagnostic support. In typical COP, corticosteroid therapy is highly
      effective; an early trial of withdrawal of treatment is appropriate because
      relapse of COP is not associated with a poor long-term outcome. Atypical forms of
      COP are outlined in this article, including focal, explosive, progressive
      fibrotic, and nonprogressive fibrotic variants. The occasional evolution of COP
      into a progressive fibrotic disorder is associated with a poor long-term outcome
      and poses particular therapeutic difficulties.

PMID- 16088693
TI  - Idiopathic interstitial pneumonias: the role of environmental triggers.
AB  - Idiopathic--or cryptogenic--fibrosing alveolitis is defined by a cluster of
      clinical, radiological, functional, and pathological features as well as by the
      exclusion of a recognized "cause.'' The processes by which clinicians assign
      causes to nonspecific diseases are complex and often subjective. Furthermore, the
      disease is comparatively rare and is generally diagnosed only after the use of
      specialized techniques. As a result, the study of its etiological factors is
      difficult and has been largely unrewarding. The distribution of the disease, so
      far as it is understood, favors the elderly and, to a lesser extent, males. In
      some countries mortality has been rising, although it is not clear whether this
      can be attributed to a diagnostic shift. Studies of occupational classifications
      among patients dying with the disease offer no striking etiological leads. Four
      potential etiologies have been formally studied: occupational dust exposures,
      cigarette smoking, prescription drug use, and viral infections. Three studies
      have indicated a role for wood and metal dust exposures; methodological issues,
      however, leave room for remaining doubt and these studies require verification in
      other populations. There is little epidemiological evidence that cigarette
      smoking contributes to the disease, or that therapeutic drug use plays an
      important part. The role of viral infections, particularly those related to
      Epstein-Barr virus (EBV), is intriguing but remains largely unsubstantiated.

PMID- 16088694
TI  - Lung and heart-lung transplantation: overview of results.
AB  - During the last decade, activity in lung transplantation increased rapidly to a
      plateau of approximately 900 transplants per year in the United States, and it is
      unlikely to increase further unless the supply of usable donor organs can be
      expanded. However, the demand for lung transplantation has continued to rise, and
      the median waiting time for lung transplantation in the United States is
      approaching 2 years. The main indications for lung transplantation have been
      chronic obstructive pulmonary disease, alpha1-antitrypsin deficiency emphysema,
      cystic fibrosis, idiopathic pulmonary fibrosis, primary pulmonary hypertension,
      and Eisenmenger's syndrome. Overall, survival after lung transplantation has been
      good, with 1-, 3-, and 5-year survival rates of 75, 58, and 44%, respectively,
      and the results have been improving. Chronic rejection and infection have been
      the main causes of medium-term mortality, and the high prevalence of chronic
      rejection remains a barrier to better outcomes. Quality of life has been enhanced
      by lung transplantation, but the posttransplantation immunosuppressive regimen
      has been associated with considerable morbidity.

PMID- 16088695
TI  - Prognostication in chronic obstructive pulmonary disease: implications for lung
      transplantation.
AB  - Chronic obstructive pulmonary disease (COPD) is the most common disease for which
      single lung transplantation (SLT) is performed and is a frequent reason for
      bilateral lung transplantation (BLT). Recent data suggest a favorable survival
      advantage for patients with COPD undergoing lung transplantation compared with
      other diagnoses. This has led some investigators to question whether
      transplantation leads to improved survival in COPD patients compared with
      alternative treatment and whether this surgical therapy is appropriate in these
      individuals. These viewpoints may reflect the difficulties inherent in accurately
      predicting short- and long-term survival in patients with advanced COPD. Our
      review of the available data suggests that clinical, physiological, and
      radiographic features allow the identification of COPD patients with increased
      mortality despite maximal medical therapy. In these high risk individuals
      transplantation remains a viable therapeutic option.

PMID- 16088696
TI  - Cystic fibrosis and bronchiectasis: selection, timing, and outcome.
AB  - Of the nearly 30,000 Cystic Fibrosis (CF) patients alive in the United States,
      more than 300 die each year. Of CF deaths at least 75% are from respiratory
      failure due to bronchiectasis. CF patients make up about 40% of the patients
      undergoing bilateral transplant. Because of the shortage of donor organs relative
      to the demand for them, it is important to choose candidates who are in the
      "transplant window.'' International criteria have been developed to assist in
      proper selection of potential candidates, but new data suggest that some
      refinement of current criteria may improve this process. Appropriate prognostic
      models, however, are not yet completely validated. Bronchiectasis patients are
      usually evaluated according to the same protocols as CF patients because no large
      studies exist that would allow us to derive separate prognostic indicators.
      Outcomes for CF patients are comparable to those for other diagnoses, except in
      the case of living donor recipients, which are slightly lower. CF patients may
      face particular issues following transplant-like infections and some
      immunosuppression complications possibly related to their underlying disease
      process. In addition, CF patients seem to be at particular risk of posttransplant
      lymphoproliferative disorder.

PMID- 16088697
TI  - Lung transplantation for cystic lung diseases: lymphangioleiomyomatosis,
      histiocytosis x, and sarcoidosis.
AB  - Lung transplantation for respiratory failure due to lymphangioleiomyomatosis,
      histiocytosis X, and sarcoidosis is a therapeutic option in selected patients.
      These indications account for less than 6% of all lung transplant procedures, and
      experience is relatively scarce. Pulmonary function testing at evaluation usually
      shows an obstructive pattern in lymphangioleiomyomatosis, whereas histiocytosis
      presents with a mixed pattern, and sarcoidosis with a restrictive pattern. Lung
      diffusion capacity is similarly reduced, however, only histiocytosis and
      sarcoidosis are often associated with pulmonary hypertension. In all three
      diseases extrapulmonary manifestations, although of different kinds, are common
      and must be investigated before transplantation to avoid posttransplant
      diagnostic pitfalls. In all these diseases, single and bilateral transplantation
      show comparable results. Typical complications in lymphangioleiomyomatosis
      include intraoperative severe intrathoracic bleeding, posttransplant chylothorax,
      pneumothorax, and bleeding of angiomyolipomas. In histiocytosis, extrapulmonary
      manifestations in bones and pituitary gland may progress. These diseases
      typically recur in the allograft, leading to clinical symptoms in histiocytosis
      whereas recurrence in lymphangioleiomyomatosis and sarcoidosis is most often
      asymptomatic. Survival is similar to patients transplanted for other diseases.

PMID- 16088698
TI  - Timing of lung transplantation for patients with fibrotic lung diseases.
AB  - Idiopathic pulmonary fibrosis (IPF) is typically a fatal disease that fails to
      respond to medical therapy. For these patients lung transplantation offers the
      promise of improved quality and duration of life. The initial reports of
      successful transplantation for IPF date back to the mid-1980s although recent
      data suggest IPF patients make up nearly 20% of all single lung transplants. The
      survival rates following lung transplantation for IPF are estimated at 67% for 1
      year, 52% for 3 years, and 35% for 5 years. Mortality rates following lung
      transplantation for IPF are higher than emphysema, but are generally comparable
      to primary pulmonary hypertension. Given the relatively high mortality following
      transplant the decision of when to transplant a patient is of paramount
      importance. Although individual patients differ, generalizations predicting a
      poor prognosis include the diagnosis of usual interstitial pneumonia (UIP), a
      forced vital capacity or total lung capacity of less than 65% predicted, a
      diffusion capacity for carbon monoxide (DL(CO)) less than 45% of predicted, and
      the presence of extensive honeycombing on high-resolution computed tomographic
      scans. The presence of any of these features should prompt the patient and
      physician to consider lung transplantation as a potential therapeutic modality.
      Patients with interstitial lung disease related to collagen vascular diseases or
      other causes need to be considered on an individual basis; their prognosis is
      usually better than patients with IPF, and the potential for systemic involvement
      may preclude listing for lung transplantation.

PMID- 16088699
TI  - Lung transplantation for pulmonary hypertension.
AB  - Although lung transplantation is a viable option for patients with end-stage
      pulmonary hypertension, it is associated with numerous problems including
      infection, rejection, and limited long-term survival. Because of these
      limitations, transplantation should only be considered for patients who are
      failing maximal medical therapy. Treatment options for patients with pulmonary
      hypertension that may serve to prolong or obviate the need for transplantation
      include anticoagulation with warfarin, diuretics, and vasodilators such as
      calcium channel blockers or continuous intravenous epoprostenol (prostacyclin).
      The response to medical therapy should be assessed at regular intervals by
      evaluating exercise tolerance and hemodynamic parameters. Because waiting periods
      for transplantation now exceed 1.5 to 2 years in the United States, and the
      response to medications is unpredictable, referral for transplantation should
      occur when patients become symptomatic. Those who are responding well to medical
      therapy should be removed from the active transplant waiting list, whereas those
      who fail therapy should go on to transplant. Utilizing medical therapy and
      transplantation as complementary treatments will achieve the best potential to
      improve quality of life and prolong survival.

PMID- 16088700
TI  - Organ procurement--strategies to optimize donor availability.
AB  - Increasing donor availability for organ transplantation requires attention to
      factors that are potentially modifiable. The potential pool of available organs
      can theoretically be enlarged by considering new sources of organs, including non
      beating heart donors, live donor lobar transplants, xenotransplants, and in vitro
      organ culture. Increased utilization of the current pool of organs can be
      achieved by creating a system that identifies, considers, and optimizes all
      possible donors. Although protocols have been drawn up regarding general and
      specifically lung donor acceptance criteria, many of these can be now recognized
      as unduly conservative and without a proven clinical basis. Careful reanalysis of
      these acceptance criteria and active donor management can be balanced against the
      particular circumstance of an individual potential recipient to increase lung
      transplantation rates.

PMID- 16088701
TI  - Chronic allograft rejection (obliterative bronchiolitis).
AB  - Lung and heart-lung transplantation are currently recognized as effective
      treatment for selected patients with end-stage lung or heart-lung disease.
      Although the survival rates have improved in recent years, long-term survival is
      still hampered by the development of chronic rejection. Histologically chronic
      rejection is manifested by obliterative bronchiolitis (OB), a process that leads
      to airways obstruction, with a gradual decline in pulmonary function tests.
      Extensive research efforts have attempted to unravel the pathophysiology of OB
      and identify key cytokines and growth factors involved in the process. Since the
      histological diagnosis of chronic rejection remains difficult, a clinical grading
      system has been proposed, determined as bronchiolitis obliterans syndrome (BOS),
      divided into four and, more recently, five categories, depending on the severity
      of airflow obstruction. This paper reviews the current knowledge of chronic
      rejection after heart-lung and lung transplantation.

PMID- 16088702
TI  - Immunosuppressive drugs and novel strategies to prevent acute and chronic
      allograft rejection.
AB  - Maintenance immunosuppression for lung transplantation includes cyclosporine or
      tacrolimus, mycophenolate mofetil or azathioprine, and prednisone. Some centers
      rely on induction agents including OKT3 (murine monoclonal antibody, OKT3), ATG
      (antithymocyte globulin), or thymoglobulin. In addition, a number of new agents
      including sirolimus (SRL) and the interleukin (IL)-2 receptor antagonists,
      daclizumab and basiliximab, have become available. Management of chronic
      rejection typically consists of augmented immunosuppression using many of the
      standard agents, and other potent agents such as methotrexate or cytoxan or more
      novel strategies including photopheresis, radiation, and total lymphoid
      irradiation (TLI).

PMID- 16088703
TI  - Parapneumonic effusions and empyema.
AB  - Parapneumonic effusions occur in up to 60% of patients hospitalized with
      community acquired pneumonia. Fortunately, the majority of these effusions follow
      an uncomplicated course responding to antibiotic therapy alone. An important
      subgroup of patients, however, follow a complicated course progressing to an
      empyema unless infected pleural fluid is drained. Decisions for drainage depend
      on host factors, the nature of the respiratory pathogen, and the extent of
      pleural inflammation and loculation. Staging of a parapneumonic effusion allows
      selection of a drainage procedure that will be most effective. Adjunctive
      therapies, such as intrapleural fibrinolysis, appear to contribute to resolution
      of pleural infection but more investigational data are needed to determine their
      specific role.

PMID- 16088704
TI  - Malignant pleural effusions.
AB  - The estimated annual incidence of malignant pleural effusions in the United
      States is 150,000 cases. Patients most commonly present with dyspnea, initially
      on exertion and later at rest. Chemical pleurodesis is the most common modality
      of therapy for patients with recurrent, symptomatic, malignant pleural effusion.
      Talc is the most successful pleurodesis agent, and talc poudrage and slurry have
      equal efficacy. Although a number of cases of acute respiratory failure have been
      associated with talc pleurodesis, the incidence is < 1% and many of these
      episodes cannot be clearly attributed to talc alone. Although a low pleural fluid
      pH is associated with a decreased survival and less successful pleurodesis, pH
      should not be the sole criterion for recommending or withholding pleurodesis.
      Other factors that need to be considered before recommending pleurodesis include
      relief of dyspnea after therapeutic thoracentesis, general health of the patient,
      performance status, presence of trapped lung, and the primary malignancy.
      Pleuroperitoneal shunt or chronic indwelling catheter should be considered for
      patients who fail pleurodesis or who have a trapped lung.

PMID- 16088705
TI  - Chylothorax.
AB  - Chylothorax or chylous pleural effusion occurs when chyle accumulates in the
      pleural space usually secondary to disruption of thoracic lymphatics. Chyle is a
      milky, white, opalescent fluid that is formed when long-chain triglycerides in
      the diet are transformed into chylomicrons and very-low-density lipoproteins,
      which are then secreted into intestinal lacteals. These lymphatic channels
      coalesce to form the thoracic duct, which transports chyle and ultimately drains
      it into the left subclavian vein. Any injury to the duct (or its major
      tributaries) as it courses through the thoracic cavity can lead to a chylous
      effusion. Diagnosis depends on direct analysis of the fluid by assaying the
      triglyceride content and, at times, lipid electrophoretic pattern (chylomicrons).
      Management depends on the underlying cause and the individual clinical
      circumstances. Nonoperative options include observation, treatment of the
      underlying disease, dietary modification employing strict medium-chain
      triglyceride diet or total parenteral nutrition, therapeutic thoracentesis, tube
      thoracostomy with chemical pleurodesis, and embolization of the thoracic duct.
      Surgical management may include pleurectomy, talc poudrage, pleuroperitoneal
      shunting, and repair or ligation of the thoracic duct via thoracoscopy or
      thoracotomy.

PMID- 16088706
TI  - Hemothorax.
AB  - Hemothorax has been recognized as a clinical entity for centuries. However, the
      use of closed drainage has only recently been described in the last 50 years.
      Chest radiography remains the mainstay of diagnosis, however computed tomography
      and ultrasound are useful in some circumstances. The treatment of hemothorax is
      adequate drainage. Drainage allows for apposition of the visceral and parietal
      pleura, which aids hemostasis. Massive hemothorax and ongoing bleeding are
      indications for thoracotomy. Clotted hemothorax can be difficult to drain
      adequately with tube thoracostomy alone. Video assisted thoracic surgery (VATS)
      has proven most effective in obtaining adequate drainage if performed early in
      the patient's course.

PMID- 16088707
TI  - Trapped lung.
AB  - Trapped lung is one of the outcomes of fibrinous or granulomatous pleuritis and
      is a cause of chronic, benign, unilateral pleural effusion. It is characterized
      by inability of the lung to expand and fill the thoracic cavity due to a
      restricting fibrous visceral pleural peel. The resulting chronic pleural space is
      fluid filled, and the persistence of the fluid is solely due to hydrostatic
      equilibrium. Historically recognized as a complication of therapeutic
      pneumothorax for treatment of tuberculosis, it is today most commonly a
      consequence of inadequately treated parapneumonic effusion, but it is also
      associated with cardiac surgery, chest trauma, and other inflammatory processes
      involving the pleura. The diagnosis requires documentation of chronicity and
      stability and the absence of an active inflammatory or malignant pleural process,
      bronchial obstruction, or severe underlying lung disease. Findings supporting the
      diagnosis are an initial negative pleural liquid pressure, increased pleural
      space elastance, and the demonstration of a pleural peel. Confirmation of the
      diagnosis requires successful surgical decortication, which is the only available
      therapy. In the asymptomatic patient, decortication is not indicated and
      observation is warranted.

PMID- 16088708
TI  - Tuberculous pleural effusion and tuberculous empyema.
AB  - Tuberculous pleuritis has increased worldwide, especially in developing
      countries, as a consequence of human immunodeficiency virus co-infection.
      Tuberculous pleuritis is a delayed hypersensitivity reaction against
      mycobacterial antigens in the pleural space. Mycobacteria are detected in less
      than 50% of pleural samples, but the characteristic pleural involvement,
      granulomas with or without caseous necrosis, is evident in 56 to 80% of cases
      from samples obtained by percutaneous pleural biopsy. Of several pleural fluid
      parameters studied, adenosine deaminase and interferon gamma (IFN-gamma) have the
      best diagnostic yield, while polymerase chain reaction remains a promising test.
      Treatment of patients with tuberculous pleuritis is discussed. Tuberculous
      empyema is a rare form of tuberculous pleuritis. It consists of a purulent
      infection of the pleural cavity with detectable bacilli in pleural fluid.
      Diagnosis is easily established clinically and bacteriologically. Treatment is to
      adequately drain the pleural space and achieve lung reexpansion, in conjunction
      with antituberculous chemotherapy. The efficacy of different surgical techniques
      is discussed.

PMID- 16088709
TI  - Pneumothorax.
AB  - Pneumothoraces are classified as spontaneous, traumatic, and iatrogenic.
      Spontaneous pneumothoraces (SP) occur without recognized lung disease (primary,
      PSP) or due to an underlying lung disease (secondary, SSP). Treatment of PSP and
      SSP has been quite heterogeneous in the United States; adoption of the recently
      published American College of Chest Physicians guidelines will hopefully improve
      care. Central to these guidelines is the emphasis of observational management of
      a small pneumothorax in clinically stable PSP patients, and chest tube placement
      as key initial management in PSP or SSP patients who are unstable or have a large
      pneumothorax. Traumatic pneumothoraces due to penetrating or nonpenetrating
      (blunt) trauma usually require the placement of a larger-bore chest tube.
      Iatrogenic pneumothoraces appear most commonly due to transthoracic needle
      aspiration and may be treated in carefully selected patients with observation.
      The presence of underlying emphysema in the setting of an iatrogenic pneumothorax
      usually mandates placement of a drainage catheter. Newer mechanical ventilation
      modes and strategies may limit the development of positive pressure ventilation-
      related iatrogenic pneumothoraces.

PMID- 16088710
TI  - Pleural effusions following cardiac injury and coronary artery bypass graft
      surgery.
AB  - This article discusses the pleural effusions that occur with the post-cardiac
      injury (Dressler's) syndrome (PCIS) and those that occur after coronary artery
      bypass graft (CABG) surgery. The PCIS can occur after any type of cardiac injury
      and is thought to be due to anti-myocardial antibodies. The primary symptoms are
      fever and chest pain, and pericarditis is frequently present. Pleural effusions
      are common with PCIS. The primary treatment for PCIS is a nonsteroidal anti
      inflammatory agent or corticosteroids. Following CABG surgery, most patients will
      have a small unilateral left-sided pleural effusion, and approximately 10% of
      patients will have a larger effusion. These large effusions can be separated into
      early effusions occurring within the first 30 days of surgery that are bloody
      exudates with a high percentage of eosinophils, and late effusions occurring more
      than 30 days after surgery that are clear yellow lymphocytic exudates. The
      primary symptom of a patient with a pleural effusion post-CABG surgery is
      dyspnea; chest pain and fever are uncommon. Most patients with large pleural
      effusions postCABG surgery are managed successfully with one to three therapeutic
      thoracenteses.

PMID- 16088711
TI  - Hepatic hydrothorax.
AB  - Hepatic hydrothorax (HH) is an uncommon manifestation of cirrhosis with ascites.
      Pleural effusions form when ascitic fluid moves through diaphragmatic defects
      that have been opened by increased peritoneal pressure. The diagnosis is
      established clinically by finding a serous transudate and is confirmed by
      radionuclide imaging demonstrating communication between the peritoneal and
      pleural spaces. In end-stage liver disease, the management of hepatic hydrothorax
      is problematic and often does not respond to medical therapy. Therapeutic options
      for a refractory hepatic hydrothorax include therapeutic thoracentesis, talc
      slurry through a chest tube, peritoneovenous and pleurovenous shunting,
      thoracoscopic talc poudrage, transjugular intrahepatic portosystemic shunt
      (TIPS), thoracosopic diaphragmatic defect repair followed by talc poudrage, and
      lastly, liver transplant. TIPS can be used as a bridge for transplantation but is
      often complicated by encephalopathy. Video assisted thoracic surgery (VATS) with
      patching the defect and talc poudrage may provide symptomatic relief; however,
      the morbidity and mortality in these extremely ill patients is high. The only
      definitive treatment for refractory hepatic hydrothorax associated with end-stage
      cirrhosis is liver transplantation.

PMID- 16088712
TI  - Persistent air leaks in patients receiving mechanical ventilation.
AB  - The term bronchopleural fistula (BPF) can be loosely defined as persistent
      leakage of gas from the airways into the pleural space. A true BPF, however, is
      located in the central airways, whereas leaks located peripherally are better
      described by the term parenchymal-pleural fistula (PPF). The presence of a
      persistent leak in a mechanically ventilated patient is a worrisome prognostic
      sign independent of the precise origin, yet it is important to distinguish BPF
      from PPF in this population. Fundamental differences in the pathogenesis and
      natural history of these two entities dictate divergent approaches to management.
      This review compares and contrasts the evaluation and management of BPF and PPF
      in patients receiving mechanical ventilation, and provides an overview of the
      many nonsurgical interventions used to manage persistent leaks.

PMID- 16088713
TI  - Antibiotic resistance: a historical perspective.
AB  - Antibiotic resistance is an increasing problem worldwide. Much of the antibiotic
      resistance occurs among community-acquired and nosocomial pulmonary pathogens.
      Antibiotic resistance may be classified as relative or absolute, which has
      important therapeutic implications. Considerable misunderstanding exists with
      regard to the factors that are responsible for antibiotic resistance. Misuse and
      overuse of antibiotics should be avoided; however, high volume of antibiotic use
      alone does not result in resistance. Antimicrobial resistance is agent specific
      and not related to antibiotic class. The antibiotics associated with a high
      resistance potential include ampicillin, cefamandole, ceftazidime, imipenem,
      ciprofloxacin, and vancomycin. The use of these antibiotics should be restricted
      to prevent generalized resistance problems. The substitution on the formulary of
      ;;vacuum cleaner'' antibiotics, along with effective infection control measures,
      can eliminate resistance problems in institutions. The key to controlling
      antibiotic resistance is to selectively use antibiotics with a low resistance
      potential and restrict those with a high resistance potential.

PMID- 16088714
TI  - Monotherapy of nosocomial pneumonia.
AB  - Nosocomial pneumonia remains a common problem and is the leading cause of death
      among patients with nosocomial infection. However, the initial empiric therapy of
      nosocomial pneumonia is directed at the leading organisms common to all patients,
      and for many patients monotherapy is adequate for at least 48 hours, at which
      time the microbiological results of appropriate diagnostic procedures should be
      known and the treatment can be focused. The currently available antimicrobial
      agents such as third- and fourth-generation cephalosporins, piperacillin plus
      tazobactam, carbapenems, and some fluoroquinolones are highly active and
      bactericidal. They should be used in consideration of current pharmacodynamic
      knowledge, which will lead to convincing clinical results. Combination of
      antibiotics is necessary only in specific situations or for the amelioration of
      special pathogens, such as Pseudomonas aeruginosa, Acinetobacter spp., and
      against mixed aerobic and anaerobic infections.

PMID- 16088715
TI  - New antibiotics in pulmonary and critical care medicine: focus on advanced
      generation quinolones and cephalosporins.
AB  - The primary goal in the treatment of respiratory tract infections is to provide
      the best possible clinical outcome for the patients. In order for this to occur,
      one must consider and synthesize a tremendous amount of data, much of it changing
      continually. Important considerations include the pharmacokinetics of the
      selected agent, its microbiological potency when used alone and in combination
      with various other agents, and the susceptibilities of the target organisms. Gram
      negative bacilli remain among the most frequent cause of bacterial infection in
      the intensive care unit and in debilitated populations. They also have the
      ability to resist the best therapies. Among the topics to be discussed here are
      the important pharmacodynamic concepts and their role in the determination of
      clinical efficacy, the newer quinolone agents, newly emerging mechanisms of
      resistance, and recent countermeasures that have been added to the therapeutic
      armamentarium. In addition, specific strategies designed to combat current
      resistance trends supported by several recent publications will be reviewed.

PMID- 16088716
TI  - Antibiotic resistance in community-acquired pulmonary pathogens.
AB  - Among infectious diseases, pneumonia is still the ;;captain of the men of
      death.'' Etiologic diagnosis is often unreliable; consequently, clinicians must
      know epidemiology of community-acquired pneumonia for optimizing empiric
      antibiotic therapy. In recent years, all major pulmonary pathogens have become
      more and more resistant to conventional antibiotics. Penicillin-resistant and
      even multiresistant pneumococci have spread worldwide, but primarily in the
      United States, some European countries, South Africa, and the Far East. A similar
      trend is evidenced by ampicillin-resistant Hemophilus influenzae, whereas
      Moraxella catarrhalis almost invariably produces beta-lactamases. The widening of
      methicillin-resistant Staphylococcus aureus from hospitals to the community may
      be the new reality of the 1990s. Increasing erythromycin resistance of
      Streptococcus pyogenes requires beta-lactam therapy. The spread of both
      cromosomally and plasmid-mediated beta-lactamases makes treatment of infections
      caused by gram-negative enterobacilli more difficult. Bacterial resistance
      creates a challenge for clinicians from the viewpoint of correct and successful
      management of patients with community-acquired pneumonia.

PMID- 16088717
TI  - Antibiotic resistance in nosocomial pulmonary pathogens.
AB  - Nosocomial pneumonia is the second most common hospital-acquired infection and
      are associated with antibiotic-resistant microorganisms. In nosocomial pneumonia,
      both the diagnosis of the disease and the identification of the pathogen agent
      are controversial. The lack of standard diagnostic criteria can lead to the
      inappropriate use of broad-spectrum antibiotic therapy and the emergence of
      multiresistant bacteria. Moreover, empirical antibiotic treatment must be
      prescribed after bacteriological sample but before culture results because the
      majority of nosocomial pneumonias require an urgent antibiotic therapy. Most
      nosocomial pneumonias are of an endogenous origin, particularly in mechanically
      ventilated patients, and this is associated with a higher rate of multiresistant
      methicillin-resistant Staphylococcus aureus, Acinetobacter baumanii, Klebsiella
      pneumoniae with extended spectrum b-lactamases, and Pseudomonadaceae. Multiple
      factors influence the frequency of pathogens associated with antibiotic
      resistance, such as duration of hospital stay, time of onset, prior antibiotic
      therapy, and local microbial ecology.

PMID- 16088718
TI  - Antibiotic side effects.
AB  - There is recent enhanced interest in the potential of medication to produce
      serious toxicity, and the television media have focused on the serious side
      effects and drug-drug interactions caused by antibiotics. In fact, a recent
      hospital study noted that drug-related toxicity was one of the most common causes
      of death for hospitalized patients. Antibiotic-induced adverse events contribute
      to host injury diagnostic confusion and excessive medical costs. In addition,
      however, a "spin-off'' of antibiotic-induced adverse events is the emergence and
      dissemination of drug-resistant organisms. This chapter will describe the adverse
      events and drug-drug interactions produced by those antibiotics that are most
      commonly prescribed to patients to prevent or treat respiratory tract infections.
      An effort will also be made to focus on those unique settings (the patient with
      renal insufficiency, the patient receiving immunosuppressive medication, the
      pregnant patient, the elderly patient, and the HIV-infected patient who is a
      candidate for primary or secondary prophylaxis for Pneumocystis carinii) that
      require a knowledge of antibiotic-induced adverse events.

PMID- 16088720
TI  - Epidemiology of chronic bronchitis and acute infective exacerbations of chronic
      bronchitis.
AB  - Acute exacerbations of chronic bronchitis (AECBs) are one of the major causes of
      morbidity and mortality in the United States, resulting in significant cost to
      the health care system. Epidemiological information on chronic bronchitis is
      abundant and has been collected in most industrialized countries. The
      epidemiology of AECB, however, is less forthcoming. The causes of AECB are
      multifactorial and include environmental pollutants, allergic responses, and
      viral and bacterial infections. The role of bacterial infection in AECB is
      controversial but is believed to account for half of AECB. Because the medical
      and economic implications of treatment failure in these patients are substantial,
      an aggressive approach to stratify and treat these patients is necessary.
      Epidemiological data on chronic bronchitis and acute infective exacerbations of
      chronic bronchitis will allow us to more precisely define the role of bacterial
      infection in AECB, and this information may help guide antimicrobial therapy.

PMID- 16088719
TI  - The antibiotic treatment of severe community-acquired pneumonia admitted to the
      critical care unit.
AB  - Community-acquired pneumonias (CAP) are still caused by Streptococcus pneumoniae,
      Hemophilus influenzae, or Moraxella catarrhalis. Legionella and Chlamydia
      pneumoniae have been defined as important atypical pathogens causing CAP.
      Klebsiella causes CAP primarily in patients with chronic alcoholism or in chronic
      care facilities. Normal hosts do not present with "unusual pathogens'' e.g.,
      Staphylococcus aureus or Pseudomonas aeruginosa. The clinical severity of a
      bacterial pneumonia has important prognostic implications and predicts admission
      to intensive care units, duration of therapy, and complications. The factors that
      determine the severity of a CAP are less related to the pathogen than the
      underlying cardiopulmonary status of the patient as well as the patient's humoral
      immunity. Relatively avirulent pathogens may result in severe CAP in patients
      with diminished/absent splenic function or significant cardiopulmonary disease. A
      critical concept is to appreciate that the selection of antimicrobial therapy is
      not dependent on co-morbidities since the antimicrobial therapy is directed
      against the pathogen and not the co-morbidities. Therefore the treatment of CAP,
      whether moderate or severe is with the same antibiotic at the same dose. Many
      antibiotic regimens are equally efficacious in the treatment of CAP. The most
      cost effective optimal regimen covers both typical and atypical pathogens, e.g.,
      levofloxacin, and is currently the preferred antibiotic approach to moderate or
      severe CAP in the CCU.

PMID- 16088721
TI  - The inflammatory response in chronic bronchitis.
AB  - Chronic bronchitis is diagnosed clinically by a chronic productive cough and is
      characterized by a variety of pathological changes, including bronchial gland
      hyperplasia, goblet cell metaplasia, and peribronchiolar fibrosis. As implied by
      the term ;;bronchitis,'' chronic airway inflammation is typically found in the
      central airways in patients with persistent cough and mucus hypersecretion.
      Although the exact pathogenesis of chronic bronchitis remains unclear, bacterial
      colonization and the resulting inflammatory response are thought to be of central
      importance. The generation of proinflammatory cytokines and chemotactic stimuli
      by the airway epithelium likely plays a central role in propagating the
      inflammatory response in patients with chronic bronchitis. Typically, an
      inflammatory mononuclear cell infiltrate is found in the airway wall, and the
      airway lumen is filled with neutrophils and their products. Further insights into
      the initiating events and underlying mechanisms that result in the clinical
      syndrome of chronic bronchitis will likely provide novel opportunities for
      therapeutic interventions.

PMID- 16088722
TI  - Infections in acute exacerbation of chronic bronchitis: what are they and how do
      we know?
AB  - Acute exacerbations of chronic bronchitis can be due to many factors. The most
      commonly recognized factor is infection, with bacterial infection being
      identified in about fifty percent of patients with chronic bronchitis. The
      causative agent can be detected by several different methods. The most common is
      sputum examination; however, more invasive techniques have been studied. These
      include transtracheal aspirates and bronchoscopic samples. The most widely
      studied bronchoscopic sample has been the protected brush specimen (PBS). Despite
      the wide array of sampling techniques, the pathogens which have been identified
      have been relatively consistent. The three most common pathogens have been H.
      influenzae, S. Pneumoniae, and B. catarrhalis. Other pathogens, including gram
      negative enteric organisms, are seen in patients with more advanced disease. The
      information obtained by the diagnostic studies has allowed clinicians to develop
      treatment strategies for AECB. These diagnostic studies will be needed to help
      upgrade treatment guidelines as new bacteria and bacterial resistance patterns
      change.

PMID- 16088723
TI  - Treatment of acute exacerbations of chronic bronchitis: antibiotic therapy.
AB  - Acute exacerbation of chronic bronchitis (AECB) is a condition associated with
      increased morbidity and mortality. Bacterial infections are the most frequent
      cause of exacerbations. The most common bacterial etiologies include Haemophilus
      influenzae, Moraxella catarrhalis, and Streptococcus pneumonia. The diagnosis of
      AECB is often based on the clinical presentation, but microbiological assessment,
      including Gram stain and sputum culture should be done. Antibiotic therapy should
      be used in patients with the following characteristics: underlying lung disease,
      frequent exacerbations, and comorbid conditions. Penicillins, erythromycin, beta
      lactamase inhibitors, and trimethoprim-sulfamethoxazole have been the preferred
      antibiotics. However, because of the increasing prevalence of resistance among
      respiratory pathogens, mainly the production of beta-lactamase by H. influenzae
      and M. catarrhalis, and the emergence of multidrug-resistant S. pneumonia, new
      generation macrolides and fluoroquinolones should be the first line of treatment
      in selected patients. These drugs have increased efficacy and safety.

PMID- 16088724
TI  - Impact of lower respiratory tract infections on health status.
AB  - Acute exacerbations of COPD have a broad range of effects on the patients in
      addition to cough and sputum production. These include malaise, increased
      dyspnea, diminished tolerance and social restriction. No single clinical or
      physiological measure captures this multiplicity of effects adequately. Health
      status measurement using instruments erroneously termed ;quality of life'
      questionnaires can provide this integrative function. Validation studies have
      shown that these scores reflect exercise capacity, respiratory symptoms,
      disability in daily life, and impaired mood. Furthermore they relate to levels of
      arterial hypoxaemia in COPD and blood leucocyte count in patients with
      bronchiectasis. Health status scores have been shown to predict hospital
      readmission or death in patients with COPD. Recent studies have shown that whilst
      sputum color and volume recover within a week of starting treatment, full
      recovery of health status may take over three months. This is consistent with the
      observation that exacerbation frequency is strongly related to health status and
      a recent report that the rate of decline in health status over time is related to
      the frequency of exacerbations. Health status instruments were developed
      originally to measure treatment efficacy, but they also provide insights into
      acute exacerbations of COPD and their clinical importance.

PMID- 16088725
TI  - Use of guidelines and risk stratification in acute exacerbations of chronic
      obstructive pulmonary disease.
AB  - Guidelines have been developed to simplify the antimicrobial treatment decision
      for patients with acute exacerbations of chronic obstructive lung disease.
      Approximately half of these patients will have a demonstrable bacterial infection
      and antibiotics have been demonstrated to shorten the clinical illness and
      prevent significant deterioration. Patients can be stratified by the risk of
      treatment failure with usual first-line antimicrobial agents. Patients presenting
      with worsening dyspnea, increased sputum volume and purulence should be offered
      antimicrobial therapy. In the presence of significant impairment of lung function
      (FEVI 50% predicted), frequent exacerbations, significant comorbidity,
      malnutrition, chronic corticosteroid administration and long duration of disease,
      should be treated with more aggressive therapy such as with a fluoroquinolone,
      amoxicillin-clavulanate, or a second or third generation cephalosporin or second
      generation macrolide. In the absence of these risk factors, first-line agents
      such as amoxicillin appear adequate. Patients with chronic suppurative airway
      disease (mainly bronchiectasis) should be treated with an antipseudomonal
      fluoroquinolone if P. aeruginosa is identified in pulmonary secretions. More
      prospective randomized trial are warranted to validate this approach.

PMID- 16088726
TI  - Bronchiolitis obliterans.
AB  - Bronchiolitis obliterans (BO) is a fibrotic lung disease involving the small
      conducting airways. BO may be classified by etiology and underlying disease or,
      more commonly, by histopathological pattern. The two major histopathological
      categories are (1) BO organizing pneumonia (BOOP) and proliferative bronchiolitis
      and (2) constrictive bronchiolitis. The former is often idiopathic in nature and
      may also be associated with connective tissue diseases and inhalation injury.
      Characteristic findings on chest imaging include alveolar infiltrates and ground
      glass opacities and pulmonary function tests (PFTs) usually reveal restrictive
      dysfunction. Constrictive bronchiolitis is associated with organ transplantation,
      infections, connective tissue diseases, inhalation injury, and drugs and may also
      have an idiopathic origin. The radiographic characteristic is a mosaic pattern on
      high-resolution computed tomography (HRCT) and PFTs most often reveal obstructive
      dysfunction. This article will attempt to review constrictive BO, including
      histopathology, clinical presentation, radiographic appearance, and physiological
      findings, for both idiopathic diseases, as well as specific clinical-associated
      entities.

PMID- 16088727
TI  - Bronchiolitis obliterans organizing pneumonia.
AB  - Bronchiolitis obliterans with organizing pneumonia (BOOP) is a pathological
      syndrome common to a variety of pulmonary inflammatory disorders. It is defined
      by the presence of buds of granulation tissue consisting of fibroblasts and
      collagen within the lumen of the distal airspaces. BOOP may be secondary to lung
      injury resulting especially from infection or drug toxicity or may develop in the
      context of connective tissue diseases or after lung or bone marrow
      transplantation. BOOP may also be idiopathic (and then preferentially called
      cryptogenic organizing pneumonia) and then is the hallmark of a distinct
      clinicoradiological syndrome of subacute pneumonia, with typical alveolar patchy
      and often migratory pulmonary opacities on imaging. Other imaging presentations
      consist of diffuse infiltrative opacities or focal pneumonia. Improvement with
      corticosteroids is usually spectacular, but relapses are common after stopping or
      while reducing treatment.

PMID- 16088728
TI  - Proportional assist ventilation.
AB  - Acute respiratory failure due to derangement of mechanical properties of
      respiratory system and/or to neuromuscular weakness has been defined as "poor
      neuroventilatory coupling.'' Proportional assist ventilation (PAV) is an
      innovative mode of partial ventilatory support designed to "amplify'' patient
      inspiratory effort and thus to restore a normal "neuroventilatory coupling.''
      Potential advantages of PAV in terms of more physiologic patient-ventilator
      interactions have been evaluated by several studies. We review the literature to
      elucidate the state of the art of the clinical implementation of PAV.

PMID- 16088729
TI  - High-frequency ventilation.
AB  - High-frequency ventilation (HFV) provides respiratory gas exchange using positive
      airway pressure-driven tidal breaths that are often smaller than anatomic dead
      space and breathing frequencies several times faster than normal. Gas transport
      with HFV involves nonconvective mechanisms such as Taylor dispersion, coaxial
      flow, and augmented diffusion. Devices to deliver HFV include the jet (an airway
      injector delivers jet pulses) and the oscillator (a piston oscillates a bias flow
      of fresh gas). The conceptual advantage to HFV is that maximal airway pressures
      are limited by the small tidal breath and lung recruitment is optimized by the
      intrinsic positive end expiratory pressure effect. Outcome has been shown to be
      improved in pediatric patients at risk for volutrauma. Adult outcome data are
      still lacking.

PMID- 16088730
TI  - Partial liquid ventilation.
AB  - Mortality from the adult respiratory distress syndrome (ARDS) and the infant
      respiratory distress syndrome remains high despite numerous interventions and
      modalities. Perfluorocarbons (PFC) are inert liquids that can dissolve large
      amounts of oxygen and carbon dioxide and can be used as respiratory media.
      Partial liquid ventilation uses PFC to partially fill the lungs of patients with
      ARDS to improve gas exchange and support them. Studies in animals and humans
      (mostly neonates) using perflubron, which is currently the only PFC approved for
      clinical use, have shown that they are safe and effective in improving
      oxygenation. In this article the rationale of the technique, its historical
      background, and animal and clinical data to date are reviewed.

PMID- 16088731
TI  - Aerosol therapy in mechanically ventilated patients: recent advances and new
      techniques.
AB  - Therapeutic aerosols are commonly used in mechanically ventilated patients, yet
      information regarding their efficacy and optimal technique of administration has
      been limited. The advantages of aerosol therapy include a smaller dose, efficacy
      comparable with that observed with systemic administration of the drug, and a
      rapid onset of action. Inhaled drugs are delivered directly to the respiratory
      tract, their systemic absorption is limited, and systemic side effects are
      minimized. Inhaled bronchodilators are routinely used with mechanically
      ventilated patients in the intensive care unit, but a variety of drugs ranging
      from antibiotics to surfactants has been administered. Nebulizers and metered
      dose inhalers (MDIs) are commonly used aerosol generators because they produce
      respirable particles with a mass median aerodynamic diameter (MMAD) between 1 and
      5 mum. Due to the limitation of available formulations, MDIs are chiefly used to
      deliver bronchodilators and steroids, whereas nebulizers have greater versatility
      and can be used to administer bronchodilators, antibiotics, surfactant,
      mucokinetic agents, and other drugs. The delivery of inhaled drugs in
      mechanically ventilated patients differs from that in ambulatory patients in
      several respects. Until recently, the consensus of opinion was that the
      efficiency of aerosol delivery to the lower respiratory tract in mechanically
      ventilated patients was much lower that that in ambulatory patients. Data suggest
      that this might be overly pessimistic and that the endotracheal tube may actually
      facilitate greater aerosol delivery compared with the normal airway when a
      variety of variables effecting aerosol delivery during mechanical ventilation are
      optimized.

PMID- 16088732
TI  - Techniques for automated feedback control of mechanical ventilation.
AB  - Mechanical ventilators have become more sophisticated with the advent of
      microprocessor control. Advances in monitoring have also improved our ability to
      harmonize patient-ventilator interaction. The next obvious step in this
      technologic progression is to turn over some decision making to the ventilator.
      In the jargon of today, we are "closing the loop.'' Ventilators have used closed
      loop control for simple tasks for the last decade. Newer closed-loop processes
      include modes that increase or decrease support based on a single-monitored
      variable. An example is the automated control of pressure support to maintain a
      deired tidal volume. More sophisticated closed-loop techniques, such as
      proportional assist ventilation and adaptive support ventilation, not only
      monitor multiple input variables but also use closed-loop control of several
      variables. This article reviews the closed-loop ventilation modes currently
      available to clinicians.

PMID- 16088733
TI  - Tracheal gas insufflation.
AB  - Tracheal gas insufflation (TGI) is an adjunct to mechanical ventilation that
      reduces CO (2) present in the anatomic deadspace. This is accomplished by flowing
      fresh gas (typically 6-10 lpm) directly into the trachea via a catheter placed
      into the endotracheal tube positioned at the distal end or by an embedded
      catheter in the wall of a specially designed endotracheal tube. This is thought
      to improve gas mixing because of the turbulent flow created at the tip of the
      catheter. There are two methods of gas flow delivery and cycling. Gas flow may be
      delivered directly toward the carina or in a reverse flow fashion. Cycling of TGI
      flow may be just during exhalation or during both inhalation and exhalation. A
      system integrated into the monitoring and controls of a mechanical ventilator
      could eventually prove the safest and most effective. However, currently there
      are no FDA-approved devices for TGI administration. It is critical to monitor the
      adverse effects (triggering, auto-PEEP [positive end expiratory pressure], air
      trapping, and patient comfort) created by the additional flow introduced into the
      ventilator circuit, while balancing the CO (2) clearance. There are limited data,
      mostly from animal studies. However, the trials done in both animal and humans
      are promising with regard to effective CO (2) elimination and avoidance of
      unacceptably high peak airway pressures. Available equipment has limited studies
      with infants. Even within the adult population, much work needs to be done to
      determine the optimal catheter position, the most appropriate TGI flow
      characteristics, and improve the safety of TGI.

PMID- 16088734
TI  - Mechanical ventilation strategies for lung protection.
AB  - A large body of animal literature has shown that lungs stretched beyond their
      normal maximum are likely to be injured and release inflammatory cytokines into
      the systemic circulation. Moreover, this injury seems to be compounded if
      alveolar collapse also occurs. This has give rise to the notion that adequate
      positive end expiratory pressure (PEEP) to prevent derecruitment coupled with a
      tidal volume-PEEP combination that limits maximal distention to below the normal
      maximum is the ideal way to provide positive pressure ventilatory support. Some
      have argued that static pressure-volume plots to describe upper and lower
      inflection points are particularly important in implementing this approach.
      Supporting this concept is the recently completed NIH trial showing improved
      survival in acute respiratory distress syndrome (ARDS) when a small tidal volume
      strategy was used.

PMID- 16088735
TI  - Pharmacologic adjuncts during mechanical ventilation.
AB  - Despite recent advances in technology, the mortality rate for patients suffering
      from adult respiratory distress syndrome remains in the range of 40-50%. This
      high mortality rate may be in part related to complications from ventilator
      management, such as ventilator-induced lung injury. In these patients, adjunct
      therapies aiming at ameliorating ventilator-induced lung injury are being
      developed. This article discusses the rationale for use of pharmacologic adjunct
      therapies, including inhaled nitric oxide, surfactant replacement therapy,
      antioxidants, prostaglandins, and corticosteroids, in patients with acute lung
      injury, and reviews the effectiveness of these agents in human clinical trials to
      date.

PMID- 16088736
TI  - Tracheal pressure ventilator control.
AB  - Tracheal pressure ventilator control (TPVC) is a ventilator mode that relies on
      tracheal pressure at the carinal end of the endotracheal tube for triggering the
      ventilator ;;on,'' controlling pressure, and cycling the ventilator ;;off.'' TPVC
      automatically nullifies imposed resistive work of the breathing apparatus
      (endotracheal tube plus ventilator) by providing automatic and variable levels of
      pressure assist. TPVC improves ventilator responsiveness for a spontaneously
      breathing patient by providing significantly higher peak inspiratory flow rates
      much closer to that demanded by a patient. TPVC also provides higher assist
      pressures and flow rates earlier in the breath and thus better-match ventilator
      supplied flow to patient-demanded flow than an equivalent level of pressure
      support ventilation. Matching patient demand for flow to ventilator supply of
      flow, early in the breath, promotes patient-ventilator synchrony and minimizes
      work of breathing. We recommend moving the pressure-triggering and control site
      to the carinal end of the endotracheal tube to provide TPVC.

PMID- 16088737
TI  - Advances in infection control: ventilator-associated pneumonia.
AB  - Mechanically ventilated patients are 6-21 times more likely to develop nosocomial
      pneumonia. It is estimated that between 6% and 52% of ventilated patients develop
      ventilator-associated pneumonia (VAP) with attributable mortality of 27-51%.
      Certain high risk organisms carry higher mortality (e.g., Pseudomonas aeruginosa
      and Acinetobacter spp.). Aspiration of colonized orodigestive secretions is the
      commonly recognized route of infection, whereas inhalation of contaminated
      aerosol hematogenous spread and direct infection are less common. Gram-negative
      pathogens are responsible for 40-60% of VAP, whereas gram-positive pathogens
      cause 15-20%, and it is commonly polymicrobial. Diagnosis remains difficult, and
      studies showed that early appropriate treatment can improve patient outcome.
      Better understanding of the pathogenesis and risk factors is important for
      implementing more effective infection control measures. Clinical trials
      evaluating outcome will help in assessing current and future preventive and
      therapeutic measures.

PMID- 16088738
TI  - Antimicrobial resistance with Streptococcus pneumoniae in the United States.
AB  - Among antimicrobial agents that have consistently been efficacious in treating
      infections due to specific bacteria over extended periods of time, there are few
      better examples than Streptococcus pneumoniae and penicillin. Until recently in
      the United States (U.S.), this combination had remained nearly uniformly
      effective. The sole issue mitigating for or against use of penicillin (or
      ampicillin) in the management of systemic pneumococcal infections, or oral
      ampicillin (or amoxicillin) in treating localized, nonlife-threatening
      pneumococcal infections, was the penicillin allergy status of the patient. In the
      nonallergic patient, penicillin or its congeners, have been the drugs of choice
      largely because resistance to these agents remained uncommon. All of that changed
      dramatically in the U.S. during the early part of the decade of the 1990s with
      the emergence of high rates of antimicrobial resistance with S. pneumoniae, and
      concomitantly, the recognition of diminished efficacy when certain other
      antimicrobials were used to treat pneumococcal infections. The intent of this
      discussion is to address a variety of specific issues that pertain to the problem
      of antimicrobial resistance with S. pneumoniae. The format chosen is a selection
      of the most asked questions regarding S. pneumoniae and antimicrobial resistance,
      and then answers are provided.

PMID- 16088739
TI  - Chlamydia pneumoniae pneumonia.
AB  - Chlamydia pneumoniae is a common cause of community-acquired pneumonia. At
      present there is no "gold'' standard for diagnosis and there is no easily
      accessible means of rapid diagnosis available. The best indication of acute C.
      pneumoniae infection is a fourfold rise in antibody titer, accompanying a
      positive polymerase chain reaction or culture. C. pneumoniae is usually
      associated with nonsevere clinical manifestations but the features will vary
      depending upon the occurrence as primary or reinfection syndrome, the presence of
      co-pathogens, or the existence of co-morbid conditions. C. pneumoniae has been
      described as a cause of severe disease requiring intensive care unit admission.
      Recommendations for therapy of C. pneumoniae pneumonia include macrolides,
      tetracyclines, or the new fluoroquinolones.

PMID- 16088740
TI  - Legionella as a cause of severe pneumonia.
AB  - Legionella pneumophila has been found to be a common cause of community-acquired
      pneumonia in patients who required intensive care unit (ICU) admission. In many
      studies, the clinical manifestations for Legionnaires' disease were more severe
      and the mortality was higher when compared with pneumonias of other etiology.
      However, this may be due to delay in diagnosis and suboptimal antibiotic therapy,
      rather than enhanced virulence of L. pneumophila. A syndromic approach using high
      fever, diarrhea, mental status changes, hyponatremia, etc., may be useful in
      suggesting the correct diagnosis in patients with severe pneumonia, but this
      remains to be validated. The availability of Legionella diagnostic microbiology
      testing in-house (rather than being sent to an outside reference laboratory)
      maximizes the ability to correctly diagnose Legionnaires' disease. All patients
      with community-acquired pneumonia admitted to an ICU should undergo Legionella
      testing using the urinary antigen and culture on selective media. Moreover, we
      recommend routine cultures of the hospital water supply once a year (regardless
      of whether a case of nosocomial Legionnaires' disease has ever been diagnosed).
      If Legionella is found in the water supply, all patients with nosocomial
      pneumonia should undergo diagnostic tests for Legionella; empiric anti-Legionella
      antibiotics should be administered pending definitive diagnosis.

PMID- 16088741
TI  - Respiratory syncytial virus infection: an emerging or unappreciated infection?
AB  - Respiratory syncytial virus (RSV) is a ubiquitous cause of respiratory infection
      with a worldwide distribution and seasonal occurrence. Natural immunity does not
      normally follow infection, and reinfection is the rule. Reinfection may even
      occur within a single season. Although its role in serious lower respiratory
      tract infection (LRTI) in infants is well recognized, the importance of RSV in
      disease of older children, adults and, especially in the elderly, is poorly
      appreciated. In large surveillance studies, RSV is at least as important in
      contributing to respiratory morbidity and mortality as influenza. These data
      would suggest that tens of millions of Americans suffer respiratory disease (LRTI
      and upper respiratory tract infection [URTI]) from RSV each winter. In addition,
      otitis media and episodic bronchospasm are complications following RSV infection.
      Unfortunately, there is no vaccine yet available for prevention. Prevention of
      disease with a hyperimmune globulin (RSVIG) and with a monoclonal antibody (MAb)
      (palivizuMab) is possible, but only for those neonates and infants at highest
      risk of morbidity and mortality from RSV infection. Therapy with the only
      approved antiviral for this indication, ribavirin, is difficult, is of
      questionable efficacy, and the compound itself is teratogenic. Infection by RSV
      constitutes an enormous but unappreciated medical need worldwide.

PMID- 16088742
TI  - Hantavirus pulmonary syndrome in the Americas: the early years.
AB  - The initial recognition of hantavirus pulmonary syndrome (HPS) as a new disease
      associated with a cluster of acute respiratory deaths among American Indians in
      the southwestern United States in 1993 bears little resemblance to the current
      understanding of this syndrome. HPS is now recognized as a zoonotic disease that
      has been endemic throughout the Americas for at least 40 years and that is
      closely linked to population densities and virus dynamics among a specific
      subfamily of rodents. The classic disease description has also been markedly
      broadened to include a spectrum of illness that ranges from asymptomatic
      infection to fulminate cardiorespiratory failure. Clinical variants with
      hemorrhagic or prominent renal manifestations have also been recognized.
      Prevention efforts have been targeted at minimizing peri-domestic contact with
      rodents and their excreta and improving clinical recognition of infection. This
      paper describes the pathogenesis underlying the profound cardiorespiratory
      compromise, person-to-person transmission reported in South America, and viable
      treatment modalities.

PMID- 16088743
TI  - Therapeutic considerations in the treatment of respiratory infections caused by
      ceftazidime-resistant Klebsiella pneumoniae.
AB  - Klebsiella pneumoniae are important human pathogens, particularly as causes of
      nosocomial respiratory tract infections. Intrinsically resistant to ampicillin,
      in recent years K. pneumoniae strains have acquired resistance to a broad variety
      of extended-spectrum cephalosporins. This resistance is most commonly mediated by
      the extended-spectrum beta-lactamases (ESBLs), plasmid-mediated enzymes that have
      evolved through point mutations in the genes encoding the more susceptible
      penicillinases TEM-1 and SHV-1. In a small minority of cases, K. pneumoniae have
      also been found to express extended-spectrum cephalosporin resistance by the
      elaboration of plasmid-mediated AmpC-type enzymes. These mutant enzymes confer
      resistance to extended-spectrum cephalosporins, penicillins, and in some cases
      cefamycins or beta-lactam-beta-lactamase inhibitor combinations. The most
      reliable and effective antimicrobial treatment of infections caused by these
      strains are the carbapenems imipenem and meropenem.

PMID- 16088744
TI  - Problem pulmonary pathogens: Pseudomonas aeruinosa.
AB  - Pseudomonas aeruginosa is a common and highly lethal agent of nosocomial
      pneumonia, especially among patients receiving mechanical ventilation. It is
      widespread in the environment and commonly recovered from water in nature and in
      hospital settings. P. aeruginosa is endowed with a formidable array of virulence
      factors that facilitate attachment to host cells, tissue invasion, and systemic
      disease. It is intrinsically resistant to many commonly used antibiotics due to a
      complex variety of mechanisms that we will briefly review. Recent advances in the
      understanding of the molecular biology of this organism have shed considerable
      light on its ability to form biofilms, which facilitate adherence especially in
      cystic fibrosis patients, and confer resistance to clearance by host immune
      mechanisms and antimicrobial killing. Treatment studies have demonstrated a
      significant risk of emergence of resistance during therapy with a variety of
      agents. Several studies suggest that two drugs are better than one for therapy of
      serious infections, although dual therapy does not always prevent emergence of
      resistant strains.

PMID- 16088745
TI  - Acinetobacter.
AB  - Members of the genus Acinetobacter are oxidase negative, aerobic Gram-negative
      coccobacilli, which have evolved taxonomically from former strains of the Mima
      Herrelia group. Their natural habitat is human skin and mucous membranes, water,
      soil, vegetation, and sewage. The most common multiresistant nosocomial pathogen
      among 19 genospecies is the A. calcoaceticus-baumannii complex ( A. baumannii).
      This species is not a common component of normal human acinetobacter
      colonization, and its ecological origin remains unknown. Outbreaks of nosocomial
      acinetobacter infection are due to spread of one or a few clones among patients,
      personnel, and the inanimate hospital environment. Thus, strict implementation of
      infection control procedures is the major technique for prevention and
      suppression of such outbreaks. Surveillance cultures of personnel and the
      environment; molecular genotyping of isolates; cohorting of colonized or infected
      patients and staff; and topical application of polymyxin B to colonized wounds
      have been used to enhance standard infection control procedures. Antimicrobial
      resistance to beta lactam antibiotics in Acinetobacter is due primarily to a
      combination of chromosomal beta lactamase production and reduced outer membrane
      permeability. Carbapenem resistance is an increasing phenomenon and restriction
      of late-generation cephalosporin and carbapenem utilization should be considered
      in outbreak control. Effective therapy of multiresistant Acinetobacter infection
      may require a variety of potentially synergistic antibiotic combinations.

PMID- 16088746
TI  - The clinical spectrum of stenotrophomonas (xanthomonas) maltophilia respiratory
      infection.
AB  - During a 15-month retrospective clinical study in an academic referral-based
      cancer center, 26 patients with S. maltophilia respiratory tract infections were
      identified (which were associated with bacteremia in 13 patients). Five of these
      26 patients had previously undescribed sinopulmonary involvement. The infections
      were typically nosocomial. Nine patients with solid tumors had malignant
      involvement of the respiratory tract (five with obstruction). In two patients,
      the infection co-existed with pulmonary aspergillosis. Fifteen patients (58%)
      died of the infection. The factors that correlated with a poor outcome included
      bacteremic pneumonia, persistent neutropenia, presence of obstruction,
      development of septic shock or multiple organ dysfunction, and delay in
      institution of appropriate antibiotic therapy. In multivariate analysis, only
      septic shock and delayed therapy remained significant. Trimethoprim
      sulfamethoxazole and/or ticarcillin-clavulanate were most commonly associated
      with a favorable outcome.

PMID- 16088747
TI  - New gene and cell-based therapies for lung cancer.
AB  - Lung cancer is the leading cause of cancer-related mortality in men and women in
      the United States, in part, because of the poor treatment options available. New
      treatment strategies that specifically target discreet steps in the molecular and
      cellular pathogenesis of this disease are under development. This review
      highlights many of the basic defects that result in the cellular transformation
      and subsequent progression of lung cancer, and how the understanding of those
      fundamental defects lead to the formulation of rational gene-based or cell-based
      therapies.

PMID- 16088748
TI  - Epidemiology of lung cancer with special reference to genetics, bioassays, women,
      and developing countries.
AB  - The twentieth century may be looked back upon as the century of lung cancer. At
      the beginning of the century lung cancer was quite rare, but this century the
      rates have increased approximately 10-fold and it is the second most common type
      of cancer and has become the leading cause of death due to cancer in the United
      States. The rate of lung cancer among U.S. women continues to rise, in contrast
      rates in U.S. men have been declining since about 1990. Cigarette smoking
      accounts for 85-90% of lung cancer deaths in the United States. However, only 10
      15% of smokers eventually develop lung cancer. In the past 25 years, since the
      U.S. Surgeon General's ground breaking report in 1964, overall smoking rates have
      been declining, but smoking still remains a significant behavior. More troubling,
      the rates of smoking continue to increase in many parts of the world. Advances in
      molecular biology and early diagnosis have increased the understanding of lung
      cancer etiology and may be effective in uncovering more efficient detection and
      treatment regimens. These advances will hopefully make lung cancer as uncommon at
      the end of the twenty-first century, as it was at the beginning of the twentieth
      century.

PMID- 16088749
TI  - Economic issues in lung cancer.
AB  - The purpose of this study is to review the economics of lung cancer management.
      The economic literature that relates to the diagnosis, treatment, and palliation
      of lung cancer as well as the pertinent methodological literature were reviewed.
      Lung cancer treatment is moderately expensive. The overall cost to society is
      significant given its high incidence. The cost of staging lung cancer can be
      minimized through the judicious use of diagnostic and staging procedures. The
      cost-effectiveness of combined modality therapy and palliative chemotherapy for
      lung cancer appears reasonable when compared with commonly accepted medical
      interventions. Based on this review, current approaches to lung cancer diagnosis
      and treatment are, for the most part, cost-effective. Reasons for inconsistent
      practice patterns in the management of lung cancer in the medical community
      should be further explored.

PMID- 16088750
TI  - Screening for lung cancer in high-risk groups: current status of low-dose spiral
      CT scanning and sputum markers.
AB  - Lung cancer is the number one cause of death from cancer in the United States.
      Currently, there is no official recommendation to screen for lung cancer even in
      high-risk populations. Accordingly, we wait for patients to present with
      symptoms. Only 15-20% of patients are stage I lung cancer at diagnosis. Past
      screening trials with chest roentgenogram and sputum cytology did not show a
      reduction of lung cancer mortality in the screened population. Since the
      completion of those trials in the early 1980s we have learned that the chest X
      ray is not sensitive at detecting lesions <2 cm in size, and patients with
      chronic obstructive pulmonary disease (COPD) have a 4- to 6-fold increased risk
      of lung cancer independent of their smoking history. Recent trials with spiral
      computed tomography (CT) scan screening have detected 80-85% of lung cancers
      while they are stage I. The problems related to spiral CT screening are the cost
      and the frequent detection of benign lesions. Algorithms are being developed to
      try and prevent unnecessary biopsies and/or surgery. Sputum cytology is currently
      the only clinically approved sputum test for detecting lung cancer. However, in
      patients with moderate dysplasia of cytology, the LIFE autofluorescence
      bronchoscopy system may yield an increased sensitivity of detecting precancerous
      or cancerous lesions. More studies are needed before the LIFE system can be
      adopted as a standard clinical tool. Currently, investigators are evaluating the
      sputum for early lung cancer detection markers. The marker that is the most
      developed is the monoclonal antibody to the heterogeneous nuclear
      ribonucleoprotein A2/B1 on the sputum epithelial cell surface. Encouraging
      preliminary results have been reported and trials are ongoing. The future looks
      bright for the field of lung cancer screening.

PMID- 16088751
TI  - Case studies in the diagnosis and staging of non-small cell lung cancer.
AB  - Lung cancer is the most common cause of cancer death in men and women. While
      overall survival rates remain dismal, survival for early stage disease approaches
      70%. Expedient, accurate staging is vital to ensure timely resection of all
      potentially curable disease. Conversely, accurate staging is important in
      preventing unnecessary surgery. While a negative clinical evaluation has a high
      negative predictive value, many clinicians routinely order conventional imaging
      to exclude distant metastases. In this article, five case vignettes are presented
      to demonstrate the international system for staging lung cancer, including the
      most recent modifications. Various tumor characteristics and patterns of lymph
      node involvement are explored to demonstrate the subtleties of staging. The
      accuracy of various diagnostic modalities in the evaluation for mediastinal and
      distant metastasis is discussed.

PMID- 16088752
TI  - Role of bronchoscopy in lung cancer.
AB  - Advancements in technology and experience have pushed forth the bronchoscope's
      increasing role in the struggle against lung cancer. The bronchoscope is useful
      in the following situations: diagnosis, staging, treatment of endobronchial
      lesions for palliation or cure, early detection of lung cancer, and research. In
      this article, we provide a concise overview of several endoscopic modalities
      (i.e., transbronchial needle aspiration, laser photoresection, photodynamic
      therapy, electrocautery, cryotherapy, brachytherapy, stents, autofluorescence
      bronchoscopy, and gene therapy). Basic principles, technique, indications,
      outcome data, and associated complications of each modality are discussed.

PMID- 16088753
TI  - Preoperative evaluation of the high-risk surgical patient for lung cancer
      resection.
AB  - Surgery is the treatment of choice for patients with stage I or II non-small cell
      carcinoma of the lung. Many such patients will have concurrent chronic
      obstructive pulmonary disease, the presence of which may increase the risk of
      lung resection. Prediction of surgical morbidity and mortality related to
      impaired pulmonary physiology should be based on evaluation of physiological
      parameters. Such measurements can be derived from a variety of studies including
      pulmonary function testing, assessment of split lung function, and measurements
      of exercise capacity. While there does not exist uniform agreement about
      threshold levels of risk related to individual tests, judicious use of widely
      available physiological measurements including FEV1, DL (CO), and V (O2)max
      should enable clinicians to make reasonable assessments of operative risk.
      Because surgery is clearly optimal treatment for stages I and II non-small cell
      lung cancer, thoughtful consideration should be given to the decision of
      operability in each individual case.

PMID- 16088754
TI  - Evidence-based outcomes for patients with non-small cell lung cancer undergoing
      resection.
AB  - Surgery plays a vital role in the management of Stages I-IIIa NSCLC. Careful
      patient selection and improved perioperative care now allow pulmonary resection
      to be performed with a very low morbidity and mortality even in older patients,
      or in patients undergoing pneumonectomy or extended operations. Most patients
      with Stage IIIb disease are not candidates for surgery, but resection can be
      curative for highly selected groups of patients with T4 tumors when these are not
      associated with nodal metastases. Surgery in conjunction with induction
      chemotherapy or chemoradiation has become a standard approach to the management
      of Stage IIIa (N2) disease and, in that setting, can be performed safely and
      effectively. The role of surgical resection in the treatment of NSCLC will
      undoubtedly continue to evolve as we gain a better understanding of the biology
      and multimodality therapy of this disease.

PMID- 16088755
TI  - Evidence-based outcomes for patients with advanced non-small cell lung cancer.
AB  - A majority of patients diagnosed with non-small cell lung cancer (NSCLC) will
      have advanced disease at diagnosis. In the past, systemic therapy (chemotherapy)
      has demonstrated only slight improvement in survival, hence, practitioners were
      reluctant to refer patients for cytotoxic therapy. In the past few years, newer
      chemotherapeutic agents, with increased activity against NSCLC, have been shown
      to significantly improve median and 1-year survival rates and improve quality of
      life. Although advanced NSCLC is considered incurable disease, it is, however,
      potentially treatable disease. This chapter will address the evidence regarding
      currently available therapies for patients with advanced stage NSCLC.

PMID- 16088756
TI  - Evaluation and management of the complications of lung cancer treatment.
AB  - The principal treatment-related complications encountered in the management of
      lung cancer are presented with particular reference to surgery, radiotherapy, and
      chemotherapy. The clinical features, risk factors, and management of the
      complications are discussed.

PMID- 16088757
TI  - Hereditary and acquired thrombophilia.
AB  - During the past decade knowledge about the etiology of venous thromboembolism has
      increased tremendously. Inherited and acquired risk factors for venous
      thromboembolism are common in patients as well as in the general population.
      Whether the presence of most of these risk factors has consequences for the
      management of symptomatic and asymptomatic individuals is not fully clear at
      present. Therefore, while searching for new thrombophilic defects, it is crucial
      to determine the absolute risk for (recurrent) venous thromboembolism as well as
      other clinical manifestations in carriers. However, tentative guidelines for
      managing patients and their families are given in this review.

PMID- 16088758
TI  - Venous thromboembolism: risk factors and prophylaxis.
AB  - Venous thromboembolism is a common disease in the community and the most frequent
      preventable cause of hospital death. Acquired and inherited risk factors for
      thrombosis have been extensively studied over the past two decades. These factors
      and the clinical setting allow the stratification of most hospitalized patients
      into low-, moderate-, and high-risk groups. For patients in the moderate- and
      high-risk categories, routine thromboprophylaxis can decrease the morbidity and
      mortality from thromboembolic complications as well as reduce patient care
      expenditures. Low-dose heparin is generally the most appropriate prophylaxis for
      moderate-risk patients, and either low molecular weight heparin or adjusted-dose
      warfarin is generally the most appropriate for high-risk patients.

PMID- 16088759
TI  - Spiral CT for pulmonary embolism.
AB  - Radiologic imaging for pulmonary embolism has been problematic. Ventilation
      perfusion scanning is frequently inconclusive; pulmonary angiography has been
      traditionally underused. Now spiral computed tomographic (CT) angiography
      provides a readily available, noninvasive test for pulmonary embolism. The
      accuracy of this examination is exceedingly high, so it should become the first
      line test for pulmonary embolism. Recent investigations reveal a high negative
      predictive value for spiral CT, further proving its value. In addition, spiral CT
      provides an alternative diagnosis in a high percentage of patients. This article
      reviews current literature regarding the sensitivity, specificity, reliability,
      consistency, and cost-effectiveness of spiral CT.

PMID- 16088760
TI  - The diagnostic approach to deep venous thrombosis.
AB  - Accurate diagnosis of deep vein thrombosis is important because untreated deep
      vein thrombosis can cause death or permanent impairment and because effective
      treatments are available. The approach to the diagnosis of deep vein thrombosis
      varies because of differences in local resources and expertise. Duplex
      ultrasonography with venous compression is the preferred initial test for the
      majority of outpatients who present with symptoms and signs that suggest acute
      deep vein thrombosis. Clinical outcome studies have shown the safety of
      withholding anticoagulants when two compression ultrasonography examinations are
      negative over a 5- to 7-day period. Alternative strategies, for example,
      combining clinical scores and D-dimer with compression ultrasonography, may also
      prove effective. In unusual circumstances, venography or even magnetic resonance
      imaging may be necessary.

PMID- 16088761
TI  - The role of the D-dimer in the diagnosis of venous thromboembolism.
AB  - Classic enzyme-linked immunosorbent assay (ELISA) D-dimer assays are sensitive in
      screening for thromboembolic disease; however, they are cumbersome and time
      consuming to perform, which limits their routine use. Latex agglutination assays
      are easier to perform, but they are not as sensitive as the ELISA assays. New D
      dimer assays incorporating novel technologies can be performed rapidly with a
      sensitivity approaching that of classic ELISA assays. D-dimer assays are
      uniformly sensitive in detecting thromboembolic disease in different patient
      populations; however, low specificity limits the clinical utility of D-dimer
      measurements in medical inpatients and postoperative patients. Increasingly,
      these measurements are being incorporated into diagnostic algorithms for venous
      thromboembolism and are reducing the need for invasive diagnostic studies.

PMID- 16088762
TI  - Low molecular weight heparins: background and pharmacology.
AB  - Low molecular weight heparins (LMWHs) are a class of drugs designed to improve on
      the therapeutic effects and complications of unfractionated heparin (UH). The two
      drug types share many structural properties and have multiple mechanisms of
      action in common. The relative potencies with which the mechanisms are expressed
      differ between LMWH and UH and among specific LMWHs. The pharmacokinetics of
      LMWHs and UH are often compared according to the results of plasma activity
      against purified factor Xa, although the correlation between ;;anti-Xa'' assays
      and the actual mechanisms of action of the drugs is questionable. Animal models
      of thrombosis give some information regarding the antithrombotic efficacy of
      different LMWHs compared with UH and with other LMWHs, but the results are varied
      and may not be applicable to human thrombosis. Similarly, clinical measurements
      of clot suppression have yielded conflicting results when the two types of
      anticoagulants have been directly compared. Numerous clinical outcome studies
      support the conclusion that subcutaneous regimens of LMWH (and of UH) are at
      least as effective and safe as intravenous UH for the treatment of clinically
      stable patients with venous thromboembolism. However, the superiority of one
      subcutaneous regimen over the others can be established only by the performance
      of well-planned comparative clinical trials.

PMID- 16088763
TI  - Treatment of acute deep venous thrombosis and pulmonary embolism: use of low
      molecular weight heparin.
AB  - Over the past decade, the use of low molecular weight heparin (LMWH) preparations
      has revolutionized the approach to preventing and treating venous
      thromboembolism. For established deep venous thrombosis, numerous prospective
      clinical trials have indicated that these drugs are at least as safe and as
      effective as standard, unfractionated heparin (UFH) and perhaps even more
      effective at preventing recurrences. Advantages of low molecular weight heparin
      include superior bioavailability compared with standard heparin, once- or twice
      daily subcutaneous delivery, and the lack of need to monitor in most clinical
      circumstances. Because of these advantages, increasing numbers of stable,
      compliant patients with deep venous thrombosis are being treated as outpatients.
      This approach requires an organized team effort with comprehensive patient
      education and carefully planned follow-up. Cost-benefit analyses have
      unequivocally proved that when treatment with low molecular weight heparin is
      utilized in the outpatient setting, there are substantial cost savings.

PMID- 16088764
TI  - The approach to massive pulmonary embolism.
AB  - Massive pulmonary embolism (PE) is surprisingly common and is not necessarily
      heralded by dramatic symptoms or signs. The death rate from PE remains high, and
      the most common cause of mortality is recurrent PE, not cancer. Prevention of
      recurrent embolism with intensive anticoagulation remains the foundation of
      therapy. The Food and Drug Administration has approved use of the low molecular
      weight heparin enoxaparin for inpatient treatment of deep venous thrombosis (DVT)
      with or without PE as a "bridge'' to warfarin. However, in patients with massive
      PE, anticoagulation alone often does not suffice to prevent death or disability
      from chronic pulmonary hypertension. Impending hemodynamic instability due to
      massive PE and its attendant ominous prognosis can be detected by rapid
      identification of moderate or severe right ventricular failure (usually easily
      with transthoracic echocardiography). Successful treatment of overt cardiogenic
      shock, manifested by systemic arterial hypotension and tachycardia, is far more
      difficult than implementing a strategy that champions early intervention after
      the onset of right ventricular failure. Among patients with massive PE,
      thrombolysis and embolectomy (often performed in the interventional angiography
      laboratory) are being used with increasing skill and improved outcomes. Intensive
      pharmacologic therapy and mechanical support devices portend a new era of
      improved intensive and multidisciplinary management of these gravely ill
      patients.

PMID- 16088765
TI  - Chronic thromboembolic pulmonary hypertension.
AB  - Under most circumstances, chronic thromboembolic pulmonary hypertension
      represents a correctable form of pulmonary hypertension. Approximately 1500
      thromboendarterectomy procedures have now been performed worldwide. Mortality
      rates reported by established programs with experience in the management of
      patients with this disease process have fallen to a range of 6 to 8%. This
      reduction in mortality has been contributed to by several factors: improved
      methods of preoperative evaluation and more selective surgical referral,
      increased surgical experience and refined techniques, and an increased
      understanding of the unique postoperative problems that occur following pulmonary
      thromboendarterectomy. Despite these advances, a great deal more needs to be
      accomplished. The early natural history and pathophysiologic mechanisms of the
      disease remain uncertain; improved diagnostic techniques are required; and the
      most feared complication of the procedure, reperfusion pulmonary edema, remains
      enigmatic in terms of its pathogenesis, prevention, and therapy.

PMID- 16088766
TI  - Venous thromboembolism: past, present and future.
AB  - Over the last four decades there have been remarkable advances in the diagnosis
      and treatment of venous thromboembolism (VTE)-pulmonary embolism (PE) and deep
      venous thrombosis (DVT). We have moved from no objective documentation to a
      plethora of ever improving imaging studies. Evolving treatment modalities have
      reduced the mortality due to PE to approximately 2%. Shorter hospitalizations
      followed by outpatient therapy are a growing reality. The use of primary
      prophylaxis is increasing, but more widespread use must be encouraged. Despite
      the many accomplishments, too many patients with VTE with its high mortality
      without treatment remain undiagnosed. There is a critical need to improve the
      role of the patient's history in identifying patients who warrant objective
      testing. The ideal would be the development of a biological marker of VTE,
      similar to the creatinine kinase-MB, creatinine kinase-MM, or troponin I in acute
      myocardial infarction.

PMID- 16088768
TI  - [Capsule endoscopy in patients with cardiac pacemakers: current situation in
      Germany].
AB  - BACKGROUND AND AIMS: The study evaluated the actually experience of capsule
      endoscopy (CE) in patients with electrical implants (cardiac
      pacemaker/defibrillator) in Germany. PATIENTS AND METHODS: A standardized
      questionnaire was sent to all centers in Germany doing capsule endoscopy. The
      questionnaire covers the number of examined patients, monitoring during CE, check
      of the electric implants before and after CE, occurrence of arrhythmia, quality
      of CE-video, complications, location and indication of CE. RESULTS: The
      questionnaire was sent to 154 hospitals and 51 surgeries. 43% of the
      questionnaires were sent back to our hospital. In 28 centers 45 Patients with a
      cardiac pacemaker (CP) and 8 patients with a defibrillator (ICD) were examined
      with CE. There were no relevant complications. In only two cases supraventricular
      extrasystoles were seen. 93% of patients with a cardiac pacemaker and 67% of the
      patients with a defibrillator were examined in a hospital. The predominant
      indication (patients with CP 86%, patients with ICD 67%) was a gastrointestinal
      bleeding. CONCLUSION: There are limited experiences of CE in patients with
      electric implants in Germany. Domain of CE is the diagnostic of gastrointestinal
      bleeding. Through the results of the inquiry you can conclude that CE in patients
      with cardiac pacemakers seems to be acceptable in the clinics.

PMID- 16088767
TI  - [Nation-wide outbreak of Salmonella Give in Germany, 2004].
AB  - PURPOSE: In spring and summer 2004, a multistate outbreak of infections caused by
      Salmonella enterica serovar Give (S. Give), a relatively rare serovar in Germany,
      was detected. In order to identify a common exposure and to describe the
      characteristics of infections caused by S. Give, an outbreak investigation was
      performed. MATERIALS AND METHODS: In addition to passive surveillance through
      mandatory case-reporting, active case-finding was conducted. A case-control study
      was undertaken in order to identify the probable vehicle of infection. S. Give
      strains were isolated and molecular subtyping was performed by pulsed-field gel
      electrophoresis (PFGE). Rates of hospitalization were assessed in patients with
      S. Give infection, and compared to the rates found in patients infected by the
      most common serovar in Germany, S. enteritidis. RESULTS: From March to July 2004,
      115 cases of gastroenteritis caused by S. Give were identified, with highest
      incidences being observed in the states of Lower Saxony and Saxony-Anhalt.
      Consumption of raw minced pork was strongly associated with S. Give infections
      (OR: 8.0; 95% CI 2.3-27.7; P = 0.001). This result was confirmed by the detection
      of common outbreak strains in isolates from both patients and pork, using PFGE.
      Infections caused by S. Give lead to hospitalization in 55% of patients > or = 60
      years, but only in 17 % of younger patients (OR: 6.0; 95% CI 2.1-16.3; P < 0.001)
      and 33% in patients > or = 60 years with infections caused by S. enteritidis (OR:
      2.5; 95% CI 1.1-5.4; P = 0.02). CONCLUSION: This is, to our knowledge, the first
      documented multistate outbreak of salmonellosis associated with the consumption
      of raw minced pork in Germany. Since contamination of pork meat with Salmonella
      cannot be avoided, people with risk factors for severe infection should generally
      avoid the consumption of raw minced pork. The high hospitalization rates in
      patients > or = 60 years infected with S. Give possibly indicate a higher
      virulence of this specific serovar. Even in non-typhoidal salmonellosis, early
      antibiotic therapy should be considered depending on infecting serovar, age and
      medical history of the patient.

PMID- 16088769
TI  - Microangiopathic hemolytic anemia (MAHA) as paraneoplastic syndrome in
      metastasized signet ring cell carcinomas: case reports and review of the
      literature.
AB  - We report on two spontaneous cases of microangiopathic hemolytic anemia (MAHA) as
      first manifestation due to metastasized signet ring carcinoma, one of gastric and
      one of unknown origin. The patients presented with an acute onset of Coombs
      negative hemolytic anemia and fragmentocytes in the peripheral blood smear which
      are typical for MAHA. These case reports present MAHA as a rare paraneoplastic
      syndrome in patients with metastasized signet ring carcinoma. Parallel to
      symptomatic treatment we started chemotherapy treatment (ELF and PLF regimen,
      respectively). In both cases we were able to control the MAHA and cancer
      progression.

PMID- 16088770
TI  - [Effects of alcohol on the upper gastrointestinal tract and the pancreas--an up
      to-date overview].
AB  - The oesophagus, stomach and pancreas are primary target organs for ethanol
      related diseases. In the oesophagus and stomach, ethanol induces motility
      disorders and mucosal lesions that are dose-dependent and reversible under acute
      conditions. Chronic consumption of alcohol causes a significant increase in the
      risk for squamous carcinoma of the oesophagus. All of these effects are mainly
      caused by direct contact of alcohol or its metabolite acetaldehyde with the
      mucosa. Non-alcoholic components are responsible for many effects of alcoholic
      beverages, including the powerful stimulation of gastric acid secretion by
      beverages that are produced by fermentation. In the exocrine pancreas, alcohol
      induces secretory alterations that are mainly affected by the manner and duration
      of alcohol exposure, the additional administration of food, the type of beverage
      or the basal secretory state of the gland. Because the pancreas is not topically
      exposed to ethanol, these ethanol effects on pancreatic secretion are primarily
      caused by systemic cholinergic mechanisms of the vagus nerve. Chronic alcohol
      abuse may cause chronic alcoholic pancreatitis after recurrent subclinical
      inflammatory episodes. Genetic predispositions are believed to play an additional
      role in the pathomechanism of the disease. In contrast to the cardiovascular
      system, moderate consumption of alcoholic beverages does not have any beneficial
      health effects on the oesophagus, stomach or pancreas. Future research needs to
      define the exact molecular mechanisms and the role of different genetic
      predispositions for alcohol-induced diseases as well as the effects of the non
      alcoholic components of alcoholic beverages.

PMID- 16088771
TI  - [Endoscopic ultrasound in chronic pancreatitis].
AB  - Endoscopic ultrasound has continuously gained importance and has proven to be of
      clinical value in patients with chronic pancreatitis. In addition, the much lower
      complication rate when compared to ERCP has to be recognised. Some authors have
      indicated that endoscopic ultrasound in the evaluation of chronic pancreatitis is
      the imaging method of choice, depending on both ductal and parenchymal criteria,
      but there are still some limitations. The two major limitations of EUS preventing
      it being the "gold standard" in patients with chronic pancreatitis are the lack
      of standard criteria to be used, and adequate education. Endoscopic ultrasound is
      difficult to learn and therefore teaching has to be standardised. A general
      acceptance of the staging of chronic pancreatitis using a catalogue based on
      criteria compatible to the Cambridge classification is required. Difficulties in
      evaluating parenchymal criteria with the exception of "indicative"
      calcifications, depend on the differentiation of the normal ageing process from
      sequelae of acute pancreatic, ethyl-toxic fibrosis and early stages of chronic
      pancreatitis. In addition, the differentiation of hypoechoic and cystic lesions
      as inflammatory changes or neoplastic tumours is still difficult; complementary
      imaging methods also have low sensitivity in this area. In conclusion, there is
      no doubt that endoscopic ultrasound has proven to be of value using an
      interdisciplinary approach in the evaluation and therapy of pseudocysts,
      peripancreatic necrosis, and pancreatic and bile duct obstruction.

PMID- 16088772
TI  - [Definitions of celiac disease--statement of an expert group from the German
      Society for Celiac Disease].
AB  - Celiac disease may have different manifestations and the clinical course can be
      very heterogeneous. Thus, management and treatment of celiac disease can be
      difficult and therefore requires individual patient care. In this article an
      expert group from the German Society for Celiac Disease (Deutsche Zoliakie
      Gesellschaft) defines the different manifestations of celiac disease. In the past
      these definitions were often used differently. The consequent usage of these
      definitions may diminish uncertainties in clinical practice and lead to a more
      standardized management of the disease which is likely to improve patient care.

PMID- 16088775
TI  - [Application of acupressure in nursing practice].
AB  - In an attempt to offer comfort, pain control and symptom management, nurses are
      increasingly offering acupressure as part of their focus on comprehensive patient
      care. According to many research reports, acupressure may be regarded as a viable
      nursing intervention. From a practical perspective, acupressure has several
      distinct advantages; it is non-invasive, free, and relatively easy to learn. Most
      importantly, since acupressure depends on neither tools nor products, it is more
      accessible than medical techniques, and easily taught to patients to enable them
      to engage in holistic self-treatment. Once patients learn the techniques
      involved, acupressure can be self-administered at home as required, thus reducing
      the dependence of patients on clinic visits. This paper provides a brief
      introduction to acupressure and its aims, and explains how it may be applied in
      nursing practice.

PMID- 16088776
TI  - [Aromatherapy in nursing practice].
AB  - Aromatherapy is the use of essential oils which are distilled from aromatic
      plants to obtain holistic effects on the mind, body, and spirit. Among nurses,
      aromatherapy is the second most commonly used complementary therapy. The chemical
      components of essential oils, such as ketones, aldehydes, and esters, determine
      the specific effects of the essential oils. Essential oils may be administered by
      inhalation, bathing, or massage to decrease anxiety, pain, and fatigue, and
      improve wound healing. As neuronal, liver, and kidney toxicity, as well as skin
      allergies may occur, it is recommended not to use essential oils on a regular
      basis. Research has provided evidence on the effects of essential oils, but
      further research is needed to identify the effects of their interaction with
      medications, and whether there are any side effects or contraindications.
      Consequently, it will provide a scientific base on the use of essential oils and
      enhance the possibilities for the use of essential oils in health care.

PMID- 16088777
TI  - [The sound of gong: the relationship between music and nursing care].
AB  - Nurses focus on individual care in order to create the beauty of unique caring
      arts. But music therapy can also play an essential role to fill the gap between
      patients' care needs and individual wants. When nurses use music therapy as an
      intervention tool, they consider the process of progress, analyzing the data to
      show the outcome. How to apply music to the care process, improving the patients'
      care quality may, therefore, become an important task in future nursing training.
      However, due to the lack of specific and accurate measurements for music therapy,
      suggestions should be made for further investigation in three directions: 1. To
      develop a suitable Taiwanese style of music therapy. 2. To understand the
      mechanism of music therapy's physical and emotional effects on humans. 3. Quality
      assurance of music therapy in nursing care.

PMID- 16088778
TI  - [Lassie's magic: animal-assisted therapy in Taiwan].
AB  - Animal-assisted therapy (AAT) is a goal-directed intervention, which involves
      placing appropriately qualified animals into the therapeutic environment of human
      patients. AAT is also a cross-professional cooperation model combining different
      health related disciplines, such as veterinary science, animal behavior,
      medicine, nursing, rehabilitation, and education. Based on concepts of concern
      for the welfare of both humans and animals, AAT provides an alternative route to
      comprehensive human health. This article describes the development and current
      state of canine Animal-Assisted Therapy in Taiwan. It covers the development of
      the relationship between humans and animals, a review of the literature about
      AAT, research, development, and outcomes in respect of the current AAT system in
      Taiwan. It also discusses practical issues concerning the AAT system, by means of
      examples. Suggestions regarding future services, professional development,
      education and research are also discussed.

PMID- 16088779
TI  - [A project to reduce mistakes in collecting specimens].
AB  - Specimen collection is an important task of nursing care. Any failure to collect
      the whole missing of a specimen may affect diagnosis and treatment. It will also
      increase the workloads of staff and the cost of medicines. From April to July
      2002, a total of 3,382 specimens were collected in A112 ward in Taipei Veterans
      General hospital. There were 43 wrong specimens, 1.27% of the total. Analysis
      showed that the reasons for the error were as follows: (1) The level of knowledge
      about the test tubes and about the volume of specimens was low. (2) The procedure
      for dealing with application from was not appropriate. (3) The box in which
      specimens were kept was not appropriate. (4) The checklist was bad. The PDCA
      process used in this project reduced the rate of wrong specimens. The strategy
      was designed with three dimensions: staff, facilities, and procedure. After it
      was implemented, the rate of wrong specimens dropped from 1.27% to 0.49%, the
      improvement rate was 61.4%, and the rate of achievement was 101.3%. This project
      not only reduced the rate of wrong specimens, but also made the process easier
      and more safisfying for staff.

PMID- 16088780
TI  - [Promoting the efficacy of discharge planning through the case management model].
AB  - Careful analysis has shown that case management in unit, has the potential to be
      improved in to reduce patient re-admission rates. The purposes of this project
      were to use case management to identify as early as possible the potential care
      problems and care needs of patients after discharge, to establish care programs,
      to arrange services and transfers, and facilitate efficient patient discharges.
      The project also provided sustainable care via telephone visiting. The project
      was divided into preparation, performance and evaluation phases. Our results
      showed that we not only improved the quality of nursing care, and the nursing
      patient relationship, but that we also dramatically increased the number of
      patients following discharge planning (from 31 to 74, an increase of 138%), and
      telephone visiting (from 31 to 253, an increase of 716%). The rate of
      satisfactions with discharge planning increased from 2.8 to 4.4, and the re
      admission rate decreased from 12.1% to 4.5%. Thus, we can see that discharge
      planning and telephone visiting are very important to improvements in service
      quality and the satisfaction of patients.

PMID- 16088781
TI  - [A woman's perception of the experience of homebirth assisted by midwife].
AB  - The purpose of this study was to understand the essence of midwife care
      throughout the pregnancy period, ending with the homebirth. Upon learning that
      the client had given birth at home, the investigator phoned her three months
      after she had done so. After having explained the purpose of this study, the
      investigator obtained the client's consent form on arrival at her house. With two
      90-minute interviews being conducted, the investigator did not consider the data
      to be complete until they stopped producing new issues. In accordance with
      Husserl's phenomenology and the steps of Colaizzi's analysis method, the data's
      rigor was sustained. Data were classified into four majors themes relating to the
      client's feelings. These were (1) receiving care in accordance with the woman's
      wishes, (2) having the right to involve herself in decision making, (3) being
      supported in her ability to give birth by herself, (4) Strengthening family
      intimacy. This study shows that homebirth can become a positive experience, only
      if the pregnant woman has got full support from her family and health
      professionals before and during the homebirth. It is suggested that homebirth
      should be encouraged for those women who are healthy and strong enough to
      undertake it.

PMID- 16088782
TI  - [Aromatherapy for dysmenorrhea].
AB  - Dysmenorrhea is one of a number of discomforts that women often suffer. Many
      kinds of complementary therapies have been discussed in the literature on the
      subject, and aromatherapy is one of these. Aromatherapy uses the action of
      essential oils refined from plants to relieve discomfort. It is effective at
      relieving the symptom distress associated with many conditions, but the
      literature contains little information about essential oils and dysmenorrhea
      relief. This paper therefore discusses several topics that may be of interest to
      women, as follows: 1. The fundamental concept of aromatherapy and its
      applications. 2. The essential oil used for dysmenorrhea relief. 3. The
      principles of essential oil recipes for dysmenorrhea relief. 4. The method for
      using essential oil for dysmenorrhea relief, and things to note.

PMID- 16088783
TI  - [Physical, psychological, social, and spiritual issues facing kidney transplant
      recipients].
AB  - Kidney Transplantation (KT) is one of the best treatments for patients with end
      stage renal disease. The "new" organ starts functioning after transplantation,
      but this doesn't mean that the patient now lives without chronic illness. On the
      contrary, the patient is actually living with another chronic disease. KT not
      only keeps patients alive, but also encourages them to live their daily lives
      well, enjoying better psychological well-being and quality of life, and playing
      role functions and taking responsibilities based on their development tasks. But,
      KT patients encounter physical problems (infection, rejection, and long-term
      complications), psychological problems (social stresses, depression, low self
      esteem, and altered family interaction), and unemployment issues. Nurses play an
      important role in assisting KT patients and should adopt appropriate
      interventions, education programs, and psychological counseling programs to help
      them to cope with their stresses. This article discusses the physical,
      psychological, spiritual, and social issues affecting KT patients and seeks to
      propose suggestions regarding future studies and KT care.

PMID- 16088784
TI  - [Developing a hospital-based asthma case management program].
AB  - The case management model, on the basis of current trends, is likely to be the
      main model for caring for chronic disease in the future. Since 2001, asthma care
      has been covered under chronic disease-management by Taiwan's Health Insurance
      Bureau. But there is no report describing a hospital-based asthma case management
      program. The purposes of this essay were to develop a hospital-based asthma case
      management model and introduce the procedures for this model: recruitment,
      monitoring, implementation, evaluation and follow-up. This model can be used as
      the standard case management model for caring for children with chronic asthma.

PMID- 16088785
TI  - [Using SWOT to analyze breastfeeding education results in a medical center].
AB  - The breastfeeding rate within the first month after postpartum dropped from 95%
      in 1962 to 25% in 1989. As a result, the Department of Health, Executive Yuan,
      has made a lot of effort to promote a baby-friendly hospital policy since 2001,
      with the aim of increasing the breastfeeding rate. However, many studies have
      pointed out that the Department of Health is encountering difficulties when
      implementing this policy. This study is designed to use the Strengths, Weakness,
      Opportunities, and Threats (SWOT) Analysis to evaluate the development of
      breastfeeding education in a certain medical center. We divide those factors that
      influence the effect of this policy into extrinsic environmental factors and
      intrinsic environmental factors. The intrinsic environmental factors are the
      strengths and weaknesses of the baby-friendly hospital policy. The extrinsic
      environmental factors are the opportunities and threats. The SWOT Matrix is also
      applied to develop appropriate strategies to take the greatest possible advantage
      of opportunities available. With the SWOT approach, managers can not only readily
      extinguish intrinsic advantages from intrinsic disadvantages, but also recognize
      external opportunities and threats. Furthermore, it assists managers in resolving
      problems and turning adversity into opportunity. In providing the SWOT analysis,
      we hope clinical nursing staff will gain a better understanding of the baby
      friendly hospital policy and deliver higher quality of health care for postpartum
      mothers, thus increasing the breastfeeding rate.

PMID- 16088786
TI  - [Physiological changes and related nursing care issues during hunger strike].
AB  - The use of hunger strike as a tool to assert grievances has been around for ages
      and has occasionally happened in the world. Hunger strikers' motives may differ,
      but their tool is the same--the voluntary refusal of food. Fasting not only
      results in body weight loss, but also in physiological and neurological function
      changes, and, of course, it may even threaten life. The health care of hunger
      strikers is complex. It involves medical staff, medical ethics and guidance for
      the management of the hunger strikers. Improper medical management may not only
      undermine the hunger striker's dignity but also risk further damage to his or her
      health. By understanding hunger strikers' physiological changes and related
      ethical issues, therefore, we aim to identify appropriate forms of nursing care
      management and guidance for the care of hunger strikers.

PMID- 16088787
TI  - [An experience nursing a patient with dengue hemorrhagic fever].
AB  - The case report presented a patient with dengue hemorrhagic fever after being
      bitten by an insect in a suburban area. The author observed and interviewed the
      patient and utilized Gorden's functional health scale to collect information,
      from Nov., 08 to Nov., 15 2002. Thrombocytopenia, febrile, and pain accompanied
      with dengue hemorrhagic fever were recorded during nursing evaluation. Lack of
      associated medical information contributed to the patient's anxiety status. The
      major nursing problems were changing of protection/ thrombocytopenia,
      hyperthermia, pain, and inadequacy of knowledge. The gum bleeding, fevers, and
      generalized bone pain were relieved by sincere listening and nursing
      intervention. In addition, medical information was delivered by way of a health
      information booklet to improve the understanding of the patient and ease the
      latter's anxiety status. Amid an increase in cases of dengue hemorrhagic fever in
      Taiwan, this case report might provide some valuable information to the nursing
      staff in order to enhance their ability to provide comprehensive care.

PMID- 16088790
TI  - Rotavirus in Asia: the value of surveillance for informing decisions about the
      introduction of new vaccines.

PMID- 16088791
TI  - Incidence of diarrhea caused by rotavirus infections in rural Zhengding, China:
      prospective, population-based surveillance.
AB  - Rotavirus is the pathogen most commonly associated with severe gastroenteritis in
      young children in the People's Republic of China, yet there are few population
      based data on the incidence of rotavirus infection. The present study
      investigated the burden of rotavirus diarrhea and rotavirus infections in rural
      China, according to age. Population-based surveillance was used to study the
      incidence of rotavirus infection among children <5 years of age in 4 townships of
      Zhengding County, Hebei Province, China. The total population in the catchment
      area in 2002 was 75,630 individuals, including 2997 children aged <5 years. Stool
      samples were obtained and were tested for rotavirus antigen by use of an enzyme
      linked immunosorbent assay. During 2002, a total of 2010 cases of diarrhea were
      detected among children <5 years of age. The incidence of treated cases of
      diarrhea was 671 cases/1000 children/year for children <5 years of age, and it
      was highest for children <12 months of age (1467 cases/1000 children/year). The
      estimated incidence of rotavirus infection was 151 cases/1000 children/year for
      children <5 years of age. The highest incidence of rotavirus infection was among
      children aged 1-2 years (340 cases/1000 children/year). Widespread immunization
      of children against rotavirus before 6 months of age should be considered for the
      control of rotavirus diarrhea.

PMID- 16088792
TI  - Incidence and burden of rotavirus gastroenteritis in Japan, as estimated from a
      prospective sentinel hospital study.
AB  - We assessed the burden of rotavirus infection-related disease, in terms of
      hospitalization and associated costs, at 3 sentinel hospitals in Akita
      prefecture, Japan. From January 2001 through December 2002, a total of 443
      children <5 years of age were hospitalized for acute gastroenteritis. Of 422
      stool specimens collected, 244 (58%) tested positive for rotavirus. Only 7.8% of
      the rotavirus disease-associated hospitalizations involved infants <6 months of
      age, whereas most cases of disease (39%) were reported in the second year of
      life, and 89% of cases had occurred by 36 months of age. The mean severity score
      for rotavirus gastroenteritis resulting in hospitalization was 16.5, according to
      the modified 20-point severity scoring system. The average associated direct
      medical cost was 136,000 yen (1236 US dollars) per case and was similar among the
      3 hospitals. The estimated incidence of rotavirus disease-associated
      hospitalizations among children <5 years of age was 7.9-17.6
      hospitalizations/1000 person-years, and the estimated cumulative incidence by 5
      years of age was 6.6%. Thus, approximately 1 in 15 children will require
      hospitalization due to rotavirus diarrhea by their fifth year of life. In Japan,
      this would mean that 78,000 children <5 years of age would be hospitalized each
      year, resulting in a direct medical cost of 10 billion yen (96 US dollars
      million). The burden associated with rotavirus gastroenteritis in Japan is
      substantial and might be reduced through the introduction of vaccines.

PMID- 16088793
TI  - Hospital-based surveillance for rotavirus diarrhea in children in Yangon,
      Myanmar.
AB  - Diarrhea is a common childhood illness in Myanmar, and rotavirus is the single
      most important etiological agent of diarrhea. Surveillance for rotavirus diarrhea
      in children <5 years of age was conducted in a tertiary pediatric hospital in
      Yangon, Myanmar, from January 2002 through December 2003. Stool specimens
      obtained from children admitted to the hospital for acute diarrhea were tested
      for the presence of rotavirus by use of an enzyme-linked immunosorbent assay.
      Diarrhea was the cause of 5671 (18%) of all hospitalizations of children <5 years
      of age during the 2-year study period (n = 30,869). Rotavirus was identified in
      923 (53%) of the 1736 stool specimens tested, and rotavirus infection was
      associated with approximately 10% of all hospitalizations of children. Rotavirus
      diarrhea most frequently occurred in children 6-17 months of age, and it was more
      commonly identified in boys (62% of children with rotavirus diarrhea were boys).
      The seasonal pattern of rotavirus disease mimicked that of diarrheal illness due
      to all causes, with the peak season for rotavirus disease occurring from November
      through February (i.e., during the cool, dry season). During the study period, 53
      of the children who were hospitalized for diarrhea died. The present study
      confirms the importance of the etiological role that rotavirus plays in childhood
      diarrhea.

PMID- 16088794
TI  - Incidence of severe rotavirus diarrhea in New Delhi, India, and G and P types of
      the infecting rotavirus strains.
AB  - A total of 62,475 children <5 years old from a defined population of
      approximately 500,000 children and adults from slums in New Delhi, India, were
      assessed for 1 year by means of passive surveillance, to identify children who
      were hospitalized for diarrhea. The incidence of severe rotavirus diarrhea was
      estimated, and the G and P types of the infecting rotavirus strains were
      determined and were correlated with the clinical severity of diarrhea. Of 584
      children who were hospitalized with diarrhea, 137 (23.5%) had rotavirus detected
      in stool specimens (incidence of rotavirus diarrhea-associated hospitalizations,
      337 hospitalizations/100,000 children <5 years of age). Most cases of diarrhea
      (98%) occurred during the first 2 years of life, peaking at 9-11 months of age.
      Rotavirus-associated diarrhea occurred year-round but was predominant in winter.
      Among the strains that could be G-typed, G1 was the most common serotype,
      followed by G9 and G2; 10% of cases of diarrhea were due to mixed G-type
      infections. Common strains identified in the present surveillance study were
      P[8]G1, P[4]G2, P[8]G9, P[6]G1, P[6]G9, and P[6]G3. Children infected with G1
      strains had a greater risk of developing more-severe cases of diarrhea than did
      children infected with other rotavirus strains (odds ratio, 2.95; 95% confidence
      interval, 1.3-6.67).

PMID- 16088795
TI  - Epidemiological profile of rotaviral infection in India: challenges for the 21st
      century.
AB  - BACKGROUND: Rotaviruses cause acute viral gastroenteritis worldwide. It has been
      estimated that, each year, 440,000 deaths that occur among children are
      attributed to rotavirus infection, mainly in developing countries. In India, the
      diversity of rotaviruses reported during the 1980s and 1990s emphasizes the need
      for surveillance of cocirculating strains, to follow the rapid changes in
      circulation and to detect novel strains. METHODS: We analyzed data from published
      epidemiological studies, to collate available information on serotyping and
      genotyping of rotaviruses before the initiation of a national rotavirus
      surveillance program. The studies included 18 Indian cities and were performed
      during 1996-2001. RESULTS: Rotaviruses were detected in 23.4% of patients with
      diarrhea who presented to the hospital. There were marked geographic differences
      in virus circulation, with G1 being the single most common G type identified in
      all parts of India, except for western India. Group B rotaviruses were reported
      from Kolkata and Pune. Human infections with strains G6, G8, G10, and G9P[19],
      which may occur as a result of zoonotic transmission of bovine and porcine
      rotaviruses, were reported from western, southern, and eastern India.
      CONCLUSIONS: The remarkable diversity of rotaviruses circulating in India
      highlights the need for uniform, widespread surveillance for rotaviruses before
      the initiation and during the implementation of immunization programs.

PMID- 16088796
TI  - Epidemiological profile and burden of rotavirus diarrhea in Vietnam: 5 years of
      sentinel hospital surveillance, 1998-2003.
AB  - For 5 years, we have conducted sentinel surveillance for rotavirus at 6 hospitals
      in 4 cities in Vietnam. Stool samples obtained from >10,000 children <5 years old
      who were admitted to the hospital with diarrhea have been screened for rotavirus.
      Overall, 55% of samples were positive, and there was little variability in rates
      of detection of rotavirus between sites (44%-62%). In Vietnam, the
      characteristics of rotavirus infection more closely resemble those seen in
      developed countries, rather than those seen in developing countries: children
      become infected at an older age, the percentage of stool samples in which
      rotavirus is detected is extremely high, and the rotavirus strains appear to be
      the common types, with fewer mixed infections occurring. It is estimated that
      5300-6800 children <5 years old die of rotavirus infection each year in Vietnam,
      representing 8%-11% of all deaths in this age group (cumulative risk per child by
      age 5 years, 1 in 200 to 1 in 285). Additional studies are ongoing to document
      the economic cost of the disease and to assess the burden of both fatal cases and
      milder cases of disease. Study outcomes will provide information for future
      testing and potential use of a rotavirus vaccine.

PMID- 16088797
TI  - Projected cost-effectiveness of rotavirus vaccination for children in Asia.
AB  - BACKGROUND: New rotavirus vaccines may soon be licensed, and decisions regarding
      implementation of their use will likely be based on the health and economic
      benefits of vaccination. METHODS: We estimated the benefits and cost
      effectiveness of rotavirus vaccination in Asia by using published estimates of
      rotavirus disease incidence, health care expenditures, vaccine coverage rates,
      and vaccine efficacy. RESULTS: Without a rotavirus vaccination program, it is
      estimated that 171,000 Asian children will die of rotavirus diarrhea, 1.9 million
      will be hospitalized, and 13.5 million will require an outpatient visit by the
      time the Asian birth cohort reaches 5 years of age. The medical costs associated
      with these events are approximately 191 million US dollars; however, the total
      burden would be higher with the inclusion of such societal costs as lost
      productivity. A universal rotavirus vaccination program could avert approximately
      109,000 deaths, 1.4 million hospitalizations, and 7.7 million outpatient visits
      among these children. CONCLUSIONS: A rotavirus vaccine could be cost-effective,
      depending on the income level of the country, the price of the vaccine, and the
      cost-effectiveness standard that is used. Decisions regarding implementation of
      vaccine use should be based not only on whether the intervention provides a cost
      savings but, also, on the value of preventing rotavirus disease-associated
      morbidity and mortality, particularly in countries with a low income level
      (according to 2004 World Bank criteria for the classification of countries into
      income groups on the basis of per capita gross national income) where the disease
      burden is great.

PMID- 16088798
TI  - Serotype diversity and reassortment between human and animal rotavirus strains:
      implications for rotavirus vaccine programs.
AB  - The development of rotavirus vaccines that are based on heterotypic or serotype
      specific immunity has prompted many countries to establish programs to assess the
      disease burden associated with rotavirus infection and the distribution of
      rotavirus strains. Strain surveillance helps to determine whether the most
      prevalent local strains are likely to be covered by the serotype antigens found
      in current vaccines. After introduction of a vaccine, this surveillance could
      detect which strains might not be covered by the vaccine. Almost 2 decades ago,
      studies demonstrated that 4 globally common rotavirus serotypes (G1-G4) represent
      >90% of the rotavirus strains in circulation. Subsequently, these 4 serotypes
      were used in the development of reassortant vaccines predicated on serotype
      specific immunity. More recently, the application of reverse-transcription
      polymerase chain reaction genotyping, nucleotide sequencing, and antigenic
      characterization methods has confirmed the importance of the 4 globally common
      types, but a much greater strain diversity has also been identified (we now
      recognize strains with at least 42 P-G combinations). These studies also
      identified globally (G9) or regionally (G5, G8, and P2A[6]) common serotype
      antigens not covered by the reassortant vaccines that have undergone efficacy
      trials. The enormous diversity and capacity of human rotaviruses for change
      suggest that rotavirus vaccines must provide good heterotypic protection to be
      optimally effective.

PMID- 16088799
TI  - Rotavirus vaccines: targeting the developing world.
AB  - For the past 2 decades, rotavirus infection, the most common cause of severe
      diarrhea in children, has been a priority target for vaccine development. This
      decision to develop rotavirus vaccines is predicated on the great burden
      associated with fatal rotavirus disease (i.e., 440,000 deaths/year), the firm
      scientific basis for developing live oral vaccines, the belief that increased
      investment in development at this time could speed the introduction of vaccines
      in developing countries, and the appreciation that implementation of a vaccine
      program should result in a measurable decrease in the number of hospitalizations
      and deaths associated with rotavirus disease within 2-3 years. RotaShield (Wyeth
      Ayerst), the first rotavirus vaccine licensed in the United States, was withdrawn
      after 9 months because of a rare association of the vaccine with the development
      of intussusception. In the developing world, this vaccine could still have had a
      measurable effect, because the benefits of preventing deaths due to rotavirus
      disease would have been substantially greater than the rare risk of
      intussusception. Two live oral vaccines being prepared by GlaxoSmithKline and
      Merck have completed large-scale clinical trials. The GlaxoSmithKline vaccine has
      been licensed in Mexico and the Dominican Republic, and the Merck vaccine could
      be licensed in the United States within 1 year; several other candidate vaccines
      are in earlier stages of testing. However, many challenges remain before any of
      these vaccines can be incorporated into childhood immunization programs in the
      developing world. First, vaccine efficacy, which has already been demonstrated in
      children in industrialized and middle-income countries, needs to be proven in
      poor developing countries in Africa and Asia. The safety of vaccines with regard
      to the associated risk of intussusception must be demonstrated as well. Novel
      financing strategies will be needed to ensure that new vaccines are affordable
      and available in the developing world. Decision makers and parents in developing
      countries need to know about this disease that has little name recognition and is
      rarely diagnosed. Finally, for the global effort toward the prevention of
      rotavirus disease to be successful, special efforts will be required in India,
      China, and Indonesia, because one-third of all deaths due to rotavirus disease
      occur in these countries, and because these countries depend almost entirely on
      vaccines manufactured domestically.

PMID- 16088800
TI  - Development of a pentavalent rotavirus vaccine against prevalent serotypes of
      rotavirus gastroenteritis.
AB  - The strategy of decreasing the morbidity and mortality associated with rotavirus
      gastroenteritis through vaccination is supported by studies demonstrating that
      wild-type rotavirus infection protects against subsequent rotavirus disease.
      Primary infection with wild-type rotavirus typically induces homotypic immunity.
      Vaccination of infants with a multivalent vaccine directed against prevalent
      rotavirus serotypes is the strategy most likely to provide the broadest degree of
      protection against rotavirus gastroenteritis. The pentavalent human-bovine
      reassortant rotavirus vaccine (HBRV) is directed against each of the most
      prevalent rotavirus serotypes, including G1, G2, G3, G4, and P1. The safety,
      immunogenicity, and efficacy of different reassortant compositions and
      formulations of the HBRV have been evaluated in clinical trials. An HBRV dose of
      > or =8 x 10(6) plaque-forming units has demonstrated 68.8%-76.6% efficacy
      against any rotavirus gastroenteritis, regardless of severity, and approximatel
      100% efficacy against severe rotavirus gastroenteritis for the first rotavirus
      infection season after vaccination. The HBRV has been generally well tolerated,
      with no increase in the incidence of fever, vomiting, diarrhea, or behavioral
      changes among vaccine recipients, compared with placebo recipients, during the 14
      and 42-day periods after administration of any dose. Shedding of vaccine strains
      in feces is uncommon. A large-scale trial is under way to evaluate the efficacy
      and safety of the manufacturing-scale formulation of pentavalent HBRV.

PMID- 16088801
TI  - A hexavalent human rotavirus-bovine rotavirus (UK) reassortant vaccine designed
      for use in developing countries and delivered in a schedule with the potential to
      eliminate the risk of intussusception.
AB  - There is an urgent need for a rotavirus vaccine, because up to 592,000 infants
      and young children <5 years old die each year from rotavirus diarrhea,
      predominantly in the developing countries. We have developed a tetravalent human
      bovine rotavirus (UK) reassortant vaccine with VP7 (G) specificity for serotypes
      1, 2, 3, and 4, which has been shown to be safe, immunogenic, and effective in
      preventing severe rotavirus diarrhea. However, because of the emergence of VP7
      (G) serotype 9 as an epidemiologically important serotype and the importance of
      VP7 (G) serotype 8 in focal areas, we are planning to add human-bovine (UK)
      reassortants with G8 and G9 specificity to the tetravalent vaccine, thereby
      formulating a "designed" hexavalent vaccine for universal use. In addition, we
      propose that the vaccine be administered orally in a 2-dose schedule, with the
      first dose given at 0-4 weeks of age and the second dose given at 4-8 weeks of
      age, when infants are relatively refractory to developing intussusception,
      thereby avoiding the age period when naturally occurring intussusception is most
      prevalent (i.e., ages 3-4 months through age 9 months). In this way, there may be
      the potential to eliminate or at least significantly decrease the risk of
      intussusception associated with rotavirus vaccination.

PMID- 16088802
TI  - Development of candidate rotavirus vaccines derived from neonatal strains in
      India.
AB  - The need for a rotavirus vaccine in India is based on the enormous burden
      associated with the >100,000 deaths due to rotavirus diarrhea that occur annually
      among Indian children. Two rotavirus strains identified during nosocomial
      outbreaks of rotavirus infection in New Delhi and Bangalore, India, more than a
      decade ago are being developed as live oral vaccines. Infected newborns had no
      symptoms, shed virus for up to 2 weeks after infection, mounted a robust immune
      response, and demonstrated protection against severe rotavirus diarrhea after
      reinfection. The 2 strains are naturally occurring bovine-human reassortants. The
      New Delhi strain, 116E, is characterized as having a P[11],G9 genotype, and the
      Bangalore strain, I321, is characterized as having a P[11],G10 genotype. The
      strains have been prepared as pilot lots for clinical trials to be conducted in
      New Delhi. This unique project, which is developing a new rotavirus vaccine in
      India with the use of Indian strains, an Indian manufacturer, and an Indian
      clinical development program, aims to expedite introduction of rotavirus vaccines
      in India.

PMID- 16088803
TI  - More on RotaShield and intussusception: the role of age at the time of
      vaccination.
AB  - BACKGROUND: RotaShield, a vaccine intended to prevent severe rotavirus diarrhea,
      was withdrawn in July 1999, 9 months after it became available in the United
      States, because of a temporal association with intussusception events that
      occurred in vaccinated infants. We explore here the effect of age on the risk of
      intussusception. METHODS: We reanalyzed a case-control database of the Centers
      for Disease Control and Prevention by use of a 21-day window, to define vaccine
      associated events. We obtained data on vaccine use from the National Immunization
      Survey and estimated the age-stratified background incidence of intussusception
      by use of Healthcare Cost and Utilization Project data. We combined these data to
      estimate how absolute risk varies with age and to model the projected population
      attributable risk associated with 3 different vaccination schedules. RESULTS: We
      found that the incidence of intussusception associated with the first dose of
      vaccine increased with age. Infants > or = 90 days old accounted for 80% of cases
      of intussusception associated with a first dose but had received only 38% of
      first doses. Modeling of the recommended schedule of vaccination at ages 2, 4,
      and 6 months projected 1 intussusception event/11,000-16,000 vaccine recipients;
      modeling of a 2-dose schedule beginning in the neonatal period projected 1
      intussusception event/38,000-59,000 vaccine recipients. CONCLUSIONS: The practice
      of initiating immunization after age 90 days, which we call "catch-up"
      vaccination, contributed disproportionately to the occurrence of intussusception
      associated with the use of RotaShield. A fully implemented 2-dose vaccination
      schedule begun during the neonatal period would lead to, at most, a 7% increase
      in the incidence of intussusception above the annual background incidence.

PMID- 16088804
TI  - Sentinel hospital surveillance for rotavirus diarrhea in Taiwan, 2001-2003.
AB  - We examined the epidemiological profile of rotavirus infection among children
      hospitalized for diarrhea in Taiwan, to assess the burden of this disease. From 1
      April 2001 through 31 March 2003, children <5 years old with gastroenteritis
      admitted to 4 sentinel hospitals were enrolled in a surveillance study and had
      stool specimens tested for the presence of rotavirus, enteric adenovirus, and the
      bacterial pathogens for which routine screening is performed. For 52% of
      patients, a recognized enteric pathogen was identified, including rotavirus (43%
      of patients), bacteria (11%), enteric adenovirus (2.5%), and a mixture of
      pathogens (3.9%). Rotavirus was detected year-round, but great month-to-month
      variability made it difficult to identify a distinct seasonal pattern. Rotavirus
      disease was most common among children 7-23 months old, but the rate of rotavirus
      detection varied little between the youngest and oldest age groups. The novel
      strain P[8]G9 was detected most commonly (37% of strains), followed by strains
      P[8]G1 (31%), P[4]G2 (10%), P[8]G3 (9.3%), and P[8]G4 (3.7%). Rotavirus infection
      is the most important cause of diarrhea among hospitalized children in Taiwan,
      and a rotavirus vaccination program for young children might significantly reduce
      this problem.

PMID- 16088805
TI  - Epidemiological profile of rotavirus infection in the Republic of Korea: results
      from prospective surveillance in the Jeongeub District, 1 July 2002 through 30
      June 2004.
AB  - To facilitate future decisions regarding the usefulness of rotavirus vaccines in
      the Republic of Korea, active surveillance was conducted in a network of clinics,
      emergency departments, and hospitals serving Jeongeub District, Korea. Children
      with diarrhea underwent standard clinical evaluations, and stool specimens were
      collected to test for the presence of rotavirus. Parents were interviewed to
      collect demographic and family information. From 1 July 2002 through 30 June
      2004, a total of 4106 children, representing 1 (50%) of every 2 children <5 years
      old in the study population, were evaluated for rotavirus diarrhea. Of the 2232
      stool specimens obtained throughout the year, 460 (20.6%) were rotavirus
      positive; however, the monthly prevalence of rotavirus infection peaked at 49.5%
      in February 2004. Of the 460 rotavirus-positive stool specimens, 366 were
      obtained from children who visited outpatient clinics, and 94 were obtained from
      children who were hospitalized. By extrapolating the proportion of rotavirus
      positive patients to all children with diarrhea in the surveillance system, we
      calculate that 882 children in Jeongeub District had rotavirus infection (which
      would predict that there would be 702 associated clinic visits and 180
      hospitalizations). Genotyping of rotavirus strains showed that 39% of strains
      were type G9P[8], 24% were type G1P[8], 17% were type G3P[8], and 13% were type
      G2P[4]. The incidence of rotavirus diarrhea peaked at age 13-24 months, and 94%
      of cases occurred during the first 3 years of life. The annual incidence of all
      rotavirus disease-associated outcomes was 56.9 cases/1000 children <5 years old
      (95% confidence interval [CI], 51.9-62.2 cases/1000 children <5 years old). The
      incidence of rotavirus disease-associated hospitalizations was 11.6 cases/1000
      children <5 years old (95% CI, 9.5-14.2 cases/1000 children <5 years old). In
      Korea, diarrhea is common during childhood, and the incidence of diarrhea due to
      rotavirus infection suggests that improved programs for the prevention and
      control of both rotavirus diarrhea and diarrhea due to other causes are needed.

PMID- 16088806
TI  - Molecular epidemiological profile of rotavirus in South Korea, July 2002 through
      June 2003: emergence of G4P[6] and G9P[8] strains.
AB  - To determine the distribution of rotavirus strain genotypes in South Korea,
      rotavirus-positive stool specimens were collected from July 2002 through June
      2003 at 8 hospitals in the Korean Rotavirus Strain Surveillance Network, and they
      were genotyped by means of reverse-transcription polymerase chain reaction. The
      globally uncommon G4P[6] type was the most prevalent type identified among
      strains (27% of strains), the newly emerging G9P[8] strain accounted for 11% of
      strains, and the globally common genotypes (i.e., G1P[8], G2P[4], G3P[8], and
      G4P[8]) constituted 55% of the strains characterized. Ninety percent of G4P[6]
      strains were detected in specimens obtained from neonates. Common genotypes were
      responsible for the rotavirus epidemic that began in January 2003 and ended in
      May 2003; however, an early peak in infections with the G4P[6] strain occurred
      from August through October 2002, and infections with this strain were detected
      throughout the remaining study period. G4P[6] strains were most commonly
      identified at 6 urban health care centers, but they were absent from 2 rural
      health care centers. The newly emerging strain G9P[8] represented a relatively
      greater proportion of strains identified at a hospital in the central region of
      Korea and at 2 hospitals in the southern region. The identification of novel
      rotavirus genotypes in this laboratory-based surveillance study underscores the
      importance to public health of continued strain surveillance among children for
      whom prevention of rotavirus infection by vaccination might be considered.

PMID- 16088807
TI  - Evaluation of RIX4414, a live, attenuated rotavirus vaccine, in a randomized,
      double-blind, placebo-controlled phase 2 trial involving 2464 Singaporean
      infants.
AB  - BACKGROUND: At present, no rotavirus vaccine is commercially available for use
      worldwide. Hence, a live, attenuated monovalent vaccine was developed with human
      strain RIX4414 (G1P1A P[8] specificity). Vaccination trials involving infants are
      ongoing in developed and developing countries. METHODS: This study was a
      randomized, double-blind, placebo-controlled trial conducted at pediatric
      hospitals and polyclinics in Singapore for the evaluation of the immunogenicity,
      reactogenicity, and efficacy of 2 oral doses of RIX4414. In total, 2464 healthy
      infants (who were 11-17 weeks old when the first dose was administered, which is
      in accordance with the local immunization schedule) were enrolled to receive
      RIX4414 at 3 concentrations of virus (10(4.7), 10(5.2), or 10(6.1) focus-forming
      units) or placebo at 1-month intervals, concomitantly with routinely administered
      infant vaccines. RESULTS: The RIX4414 vaccine was highly immunogenic, and
      virtually all vaccine recipients (98%-100%) experienced "vaccine take" (i.e., a
      combined immunogenicity end point based on seroconversion and/or shedding of
      RIX4414 in postvaccination stool samples) after receipt of 2 doses at all 3
      dosage levels. Depending on the virus concentration, the anti-rotavirus IgA
      seroconversion rate varied from 76% (95% confidence interval [CI], 68%-83%) to
      91% (95% CI, 85%-95%). Two doses of RIX4414 were well tolerated, with no increase
      in high fever, severe diarrhea, or vomiting after either dose or with increased
      viral concentration, compared with placebo. There was no observed interference
      with routine vaccinations of infants when RIX4414 was coadministered. The
      calculated efficacy of RIX4414 against rotavirus gastroenteritis was 82% (P =
      .046); however, this result was considered to be of limited conclusive value
      because of the low number of rotavirus gastroenteritis episodes identified during
      the follow-up period. CONCLUSIONS: The live, attenuated rotavirus vaccine
      (RIX4414) was well tolerated and highly immunogenic in Singaporean infants. The
      immunogenicity of routinely administered infant vaccines was not impaired by
      concomitant administration of RIX4414 vaccine.

PMID- 16088808
TI  - Hospital-based study of the economic burden associated with rotavirus diarrhea in
      Hong Kong.
AB  - BACKGROUND: Rotavirus infection is the most common cause of severe diarrhea in
      both developed and developing countries. METHODS: To estimate the economic burden
      associated with rotavirus infection in Hong Kong, we combined data on the disease
      burden of rotavirus-associated hospital admissions with detailed cost data for a
      subsample of 471 children with diarrhea admitted to hospitals. RESULTS: The
      annual total social cost and total direct medical cost for rotavirus-associated
      admissions were calculated as 4.3 US dollars and 4 million US dollars,
      respectively, by use of data collected during March 2001 to March 2003. The
      estimate of the direct medical costs was approximately 4-fold higher than a
      previous estimate; this difference largely reflects the greater disease burden
      identified through active disease surveillance conducted under the auspices of
      the Asian Rotavirus Surveillance Network. On average, families spent 120 US
      dollars when their child's admission was associated with rotavirus infection;
      this cost represents approximately 10% of the monthly salary of an unskilled or
      service worker. CONCLUSIONS: These data emphasize the potential for a safe and
      effective rotavirus vaccine to reduce the economic burden associated with
      rotavirus disease.

PMID- 16088809
TI  - Estimates of rotavirus disease burden in Hong Kong: hospital-based surveillance.
AB  - BACKGROUND: We conducted prospective, hospital-based surveillance for rotavirus
      disease for a 2-year period at 4 of 12 public government (Hospital Authority
      [HA]) hospitals in Hong Kong. It has been estimated that HA hospitals provide 90%
      of inpatient care in Hong Kong. METHODS: Information was collected for children
      <5 years old who had a primary or secondary diagnosis of diarrhea or for whom a
      stool sample was tested for the presence of rotavirus (by enzyme immunoassay) or
      bacteria (by culture). Surveillance data were compared with routine discharge
      information from the HA's computerized Clinical Management System (CMS). RESULTS:
      During a 2-year period (1 April 2001 through 31 March 2003), 7391 children were
      admitted to the hospital with diarrhea or developed diarrhea during their
      hospital stay. Of these children, 5881 (80%) had a stool sample tested for the
      presence of rotavirus, and 30% were positive for rotavirus (representing 24% of
      all diarrhea-associated admissions). CMS data underreported the total percentage
      of diarrhea-associated admissions (15% vs. 20%) and the percentage of diarrhea
      associated admissions that were the result of rotavirus infection (13% vs. 24%).
      Estimated rates of hospitalization for rotavirus infection (8.8 admissions/1000
      children <5 years old and 18.4 admissions/1000 children <1 year old) were 4-fold
      higher than our previous estimates, which were determined on the basis of CMS
      data alone. We estimate that the cumulative risk of hospitalization with
      rotavirus diarrhea by age 5 years is 1 in 24. Combined active and passive (CMS)
      surveillance data indicate that 4.6% of all general pediatric admissions to HA
      hospitals in Hong Kong were associated with rotavirus infection. CONCLUSION: Our
      study combined passive surveillance data from all Hong Kong HA hospitals with
      active surveillance data from 4 sentinel hospitals. The estimates of rotavirus
      disease burden obtained will help emphasize the effect of this important disease
      and create awareness of the potential for rotavirus vaccines. The surveillance
      model developed could also be a powerful tool for monitoring the effect of a
      vaccine.

PMID- 16088810
TI  - Estimates of the burden of rotavirus disease in Malaysia.
AB  - BACKGROUND: Accurate national estimates of the disease burden associated with
      rotavirus diarrhea are essential when considering implementation of a rotavirus
      vaccination program. We sought to estimate rotavirus disease-associated morbidity
      and mortality in Malaysia, using available sources of information. METHODS: We
      analyzed national data from the Ministry of Health (Kuala Lumpur, Malaysia) to
      derive rates of hospitalization, clinic visits, and deaths related to acute
      gastroenteritis (AG) among children <5 years of age. The number of events
      attributable to rotavirus infection was estimated by multiplying age-stratified
      rates of detection of rotavirus from 2 hospital surveillance sites by national
      data. RESULTS: In 1999 and 2000, an average of 13,936 children (1 in 187
      children) were hospitalized annually for AG. Surveillance of visits to outpatient
      clinics for AG identified an average of 60,342 such visits/year between 1998 and
      2000. The AG-associated mortality rate was 2.5 deaths/100,000 children. On the
      basis of the finding that 50% of children were hospitalized for rotavirus
      diarrhea, we estimated that 1 in 61 children will be hospitalized for rotavirus
      disease and that 1 in 37 children will seek treatment as an outpatient.
      CONCLUSIONS: Among Malaysian children, there is a significant burden associated
      with AG- and rotavirus disease-related hospitalizations and outpatient visits,
      and this burden potentially could be prevented by the use of rotavirus vaccines.

PMID- 16088811
TI  - Epidemiology and burden of rotavirus diarrhea in Thailand: results of sentinel
      surveillance.
AB  - Diarrhea remains an important cause of morbidity and mortality among children in
      Thailand, with >1 million cases reported in 2002. In anticipation of the
      development of vaccines against rotavirus, we evaluated the disease burden
      associated with rotavirus infection in Thai children and evaluated the rotavirus
      serotypes now circulating in Thailand. Diarrhea surveillance was conducted at 6
      Thai hospitals in different geographic areas. Community-based surveillance was
      conducted in Huaykrajao District, Kanchanaburi Province. During the 24 months of
      surveillance, 4057 children were admitted to the 6 participating hospitals, and
      1950 stool samples were collected. Of these stool samples, 43% (838) were
      positive for rotavirus. All rotavirus-positive stool samples were evaluated to
      identify their serotypes; 54.8% of samples were of serotype G9, which was
      predominant each year. Other identified rotavirus serotypes included G2, G4, G1,
      and G3 (17.2%, 5.3%, 0.8%, and 0.1% of isolates, respectively). Approximately one
      half of the children hospitalized with rotavirus diarrhea were <1 year old.
      Community surveillance showed the proportion of cases of rotavirus diarrhea in
      the community to be much lower than that in the hospitalized population (12.2%
      vs. 43.0%).

PMID- 16088812
TI  - Sentinel hospital surveillance for rotavirus diarrhea in the People's Republic of
      China, August 2001-July 2003.
AB  - China has the second largest birth cohort in the world and the second highest
      number of deaths due to rotavirus infection. It is also the only country with a
      licensed rotavirus vaccine. Chinese policy makers now need credible estimates of
      the burden of rotavirus disease, to decide about vaccine use. From August 2001
      through July 2003, prospective hospital-based surveillance for rotavirus diarrhea
      among children <5 years of age was conducted in 6 sentinel hospitals. Rotavirus
      isolates were characterized to determine the G and P genotypes circulating during
      the study. Of 3149 children who were admitted to the hospitals for diarrhea and
      for whom screening for rotavirus was performed, 1590 (50%) had positive results
      of an antigen detection assay. Of all episodes of rotavirus diarrhea, 95%
      occurred during the first 2 years of life. The most common rotavirus strain was
      P[8]G3 (49% of episodes), and all the common strains were detected, including G9
      strains (4% of episodes). Ongoing efforts are under way to more precisely define
      the burden of rotavirus diarrhea in urban and rural populations, to assess the
      proportion of episodes that may be due to unusual or emerging strains, and to
      estimate the economic burden of rotavirus disease.

PMID- 16088819
TI  - Combination antiretroviral therapy in african nursing mothers and drug exposure
      in their infants: new pharmacokinetic and virologic findings.

PMID- 16088820
TI  - Highly active antiretroviral therapy started during pregnancy or postpartum
      suppresses HIV-1 RNA, but not DNA, in breast milk.
AB  - BACKGROUND: The ability of highly active antiretroviral therapy (HAART) to reduce
      human immunodeficiency virus type 1 (HIV-1) RNA and DNA in breast milk has not
      been described. METHODS: We compared breast-milk HIV-1 RNA and DNA loads of women
      in Botswana who received HAART (nevirapine, lamivudine, and zidovudine) and women
      who did not receive HAART. RESULTS: Women in the HAART group received treatment
      for a median of 98 days (range, 67-222 days) at the time of breast-milk sampling;
      23 (88%) of 26 had whole breast-milk HIV-1 RNA loads <50 copies/mL, compared with
      9 (36%) of 25 women who did not receive HAART (P=.0001). This finding remained
      significant in a multivariate logistic-regression model (P = .0006). The whole
      milk HIV-1 DNA load was unaffected by HAART. Of women who received HAART, 13
      (50%) of 26 had HIV-1 DNA loads <10 copies/10(6) cells, compared with 15 (65%) of
      23 who did not receive HAART (P = .39). CONCLUSIONS: HAART suppressed cell-free
      HIV-1 RNA in breast milk and may therefore reduce mother-to-child transmission
      (MTCT) of HIV-1 via breast-feeding. However, HAART initiated during pregnancy or
      early after delivery had no apparent effect on cell-associated HIV-1 DNA loads in
      breast milk. Clinical trials to determine MTCT among breast-feeding women
      receiving HAART are needed.

PMID- 16088821
TI  - Antiretroviral concentrations in breast-feeding infants of women in Botswana
      receiving antiretroviral treatment.
AB  - BACKGROUND: The magnitude of infant antiretroviral (ARV) exposure from breast
      milk is unknown. METHODS: We measured concentrations of nevirapine, lamivudine,
      and zidovudine in serum and whole breast milk from human immunodeficiency virus
      type 1 (HIV-1)-infected women in Botswana receiving ARV treatment and serum from
      their uninfected, breast-feeding infants. RESULTS: Twenty mother-infant pairs
      were enrolled. Maternal serum concentrations of nevirapine were high (median,
      9534 ng/mL at a median of 4 h after nevirapine ingestion). Median breast-milk
      concentrations of nevirapine, lamivudine, and zidovudine were 0.67, 3.34, and
      3.21 times, respectively, those in maternal serum. The median infant serum
      concentration of nevirapine was 971 ng/mL, at least 40 times the 50% inhibitory
      concentration and similar to peak concentrations after a single 2-mg/kg dose of
      nevirapine. The median infant serum concentration of lamivudine was 28 ng/mL, and
      the median infant serum concentration of zidovudine was 123 ng/mL, but infants
      were also receiving zidovudine prophylaxis. CONCLUSIONS: HIV-1 inhibitory
      concentrations of nevirapine are achieved in breast-feeding infants of mothers
      receiving these ARVs, exposing infants to the potential for beneficial and
      adverse effects of nevirapine ingestion. Further study is needed to understand
      the impact of maternal ARV treatment on breast-feeding HIV-1 transmission, infant
      toxicity, and HIV-1 resistance mutations among infected infants.

PMID- 16088822
TI  - Elevated T cell counts and RANTES expression in the genital mucosa of HIV-1
      resistant Kenyan commercial sex workers.
AB  - The initial site of exposure to human immunodeficiency virus (HIV)-1 during
      heterosexual transmission occurs in the genital tract. Although the majority of
      immunological studies have focused on the immune response to HIV-1 at the
      systemic level, our understanding of tissue-specific immunity is deficient. The
      goal of the present study was to characterize T cell populations found in the
      cervix of women shown to be resistant to infection by HIV-1. Levels of both
      systemic and cervical mucosal lymphocytes were compared between HIV-1-resistant,
      HIV-1-uninfected, and HIV-1-infected commercial sex workers (CSWs) as well as HIV
      1-uninfected non-CSW control subjects at low risk for exposure. The HIV-1
      resistant CSWs had increased cervical CD4+ and CD8+ T cell counts, compared with
      the HIV-1-uninfected CSWs; importantly, these increases were not reflected in the
      systemic lymphocyte compartment. There was a 2-fold increase in CD4+ T cell
      counts in the HIV-1-resistant CSWs, compared with both the HIV-1-infected and the
      HIV-1-uninfected CSWs. Expression of the HIV-1 coreceptors CCR5 and CXCR4 was
      also determined, and cytokine and beta chemokine levels in the genital mucosa
      were assessed. The HIV-1-resistant CSWs had a 10-fold increase in RANTES
      expression, compared with the HIV-1-uninfected CSWs. This is the first study to
      show elevated levels of beta chemokines and CD4+ T cells in the genital tracts of
      women who are exposed to HIV-1 and yet are uninfected.

PMID- 16088823
TI  - Low CD4 T cell counts before HIV-1 seroconversion do not affect disease
      progression in Ethiopian factory workers.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1)-uninfected Ethiopians
      have lower CD4 T cell counts than do other populations in Africa and
      industrialized countries. We studied whether this unique immunological profile
      results in shorter survival times in HIV-1-infected Ethiopians. METHODS: Data
      from an open cohort study of 149 HIV-1-infected factory workers in Ethiopia for
      1997-2002 were used. To estimate survival times, a continuous-time Markov model
      was designed on the basis of CD4 T cell counts and World Health Organization
      clinical staging. By use of a random-effects model, decline in CD4 T cell counts
      was compared between HIV-1-infected Ethiopian and Dutch individuals. RESULTS:
      Median survival times were in the range of 9.1-13.7 years, depending on the
      approach used. This range is similar to that for populations in industrialized
      countries before the advent of antiretroviral therapy. Ethiopians had a lower
      annual decline in CD4 T cell counts than did Dutch individuals, which remained
      when groups with similar CD4 T cell count categories were compared. Moreover, the
      slower decline in CD4 T cell counts was not due merely to lower HIV-1 RNA loads
      or an absence of syncytium-inducing/X4 HIV-1 subtype C strains in Ethiopians.
      CONCLUSIONS: Low baseline CD4 T cell counts do not imply shorter survival times
      in Ethiopians than in other populations, presumably because of a slower decline
      in CD4 T cell counts.

PMID- 16088824
TI  - Cytolytic T lymphocytes (CTLs) from HIV-1 subtype C-infected Indian patients
      recognize CTL epitopes from a conserved immunodominant region of HIV-1 Gag and
      Nef.
AB  - Analysis of the human immunodeficiency virus type 1 (HIV-1) cytolytic T
      lymphocyte (CTL) epitopes recognized by the targeted population is critical for
      HIV-1 vaccine design. Peripheral blood mononuclear cells from 47 Indian subjects
      at different stages of HIV-1 infection were tested for HIV-1 Gag-, Nef-, and Env
      specific T cell responses by interferon (IFN)- gamma enzyme-linked immunospot
      (ELISPOT) assay, using pools of overlapping peptides. The Gag and Nef antigens
      were targeted by 83% and 36% of responders. Five immunodominant regions, 4 in Gag
      and 1 in Nef, were identified in the study; these regions are conserved across
      clades, including the African subtype C clade. Three antigenic regions were also
      found to be recognized by CTLs of the study participants. These regions were not
      identified as immunodominant regions in studies performed in Africa, which
      highlights the importance of differential clustering of responses within HIV-1
      subtype C. Twenty-six putative epitopes--15 Gag (10 in p24 and 5 in p17), 10 Nef,
      and 1 Env (gp 41)--were predicted using a combination of peptide matrix ELISPOT
      assay and CTL epitope-prediction software. Ninety percent of the predicted
      epitopes were clustered in the conserved immunodominant regions of the Gag and
      Nef antigens. Of 26 predicted epitopes, 8 were promiscuous, 3 of which were
      highly conserved across clades. Three Gag and 4 Nef epitopes were novel. The
      identification of conserved epitopes will be important in the planning of an HIV
      1 vaccine strategy for subtype C-affected regions.

PMID- 16088825
TI  - Genome sequence of a serotype M28 strain of group a streptococcus: potential new
      insights into puerperal sepsis and bacterial disease specificity.
AB  - Puerperal sepsis, a major cause of death of young women in Europe in the 1800s,
      was due predominantly to the gram-positive pathogen group A Streptococcus.
      Studies conducted during past decades have shown that serotype M28 strains are
      the major group A Streptococcus organisms responsible for many of these
      infections. To begin to increase our understanding of their enrichment in
      puerperal sepsis, we sequenced the genome of a genetically representative strain.
      This strain has genes encoding a novel array of prophage virulence factors, cell
      surface proteins, and other molecules likely to contribute to host-pathogen
      interactions. Importantly, genes for 7 inferred extracellular proteins are
      encoded by a 37.4-kb foreign DNA element that is shared with group B
      Streptococcus and is present in all serotype M28 strains. Proteins encoded by the
      37.4-kb element were expressed extracellularly and in human infections.
      Acquisition of foreign genes has helped create a disease-specialist clone of this
      pathogen.

PMID- 16088826
TI  - Evolutionary origin and emergence of a highly successful clone of serotype M1
      group a Streptococcus involved multiple horizontal gene transfer events.
AB  - To better understand the molecular events involved in the origin of new
      pathogenic bacteria, we studied the evolution of a highly virulent clone of
      serotype M1 group A Streptococcus (GAS). Genomic, DNA-DNA microarray, and single
      nucleotide polymorphism analyses indicated that this clone evolved through a
      series of horizontal gene transfer events that involved (1) the acquisition of
      prophages encoding streptococcal pyrogenic exotoxin A and extracellular DNases
      and (2) the reciprocal recombination of a 36-kb chromosomal region encoding the
      extracellular toxins NAD+-glycohydrolase (NADase) and streptolysin O (SLO). These
      gene transfer events were associated with significantly increased production of
      SLO and NADase. Virtual identity in the 36-kb region present in contemporary
      serotype M1 and M12 isolates suggests that a serotype M12 strain served as the
      donor of this region. Multiple horizontal gene transfer events were a crucial
      factor in the evolutionary origin and emergence of a very abundant contemporary
      clone of serotype M1 GAS.

PMID- 16088827
TI  - Specific C-terminal cleavage and inactivation of interleukin-8 by invasive
      disease isolates of Streptococcus pyogenes.
AB  - Lethal necrotizing fasciitis caused by Streptococcus pyogenes is characterized by
      a paucity of neutrophils at the site of infection. Interleukin (IL)-8, which is
      important for neutrophil transmigration and activation, can be degraded by S.
      pyogenes. Blood isolates of S. pyogenes were better able to degrade human IL-8
      than throat isolates. Degradation of IL-8 was the result of a single specific
      cleavage between 59glutamine and 60arginine within the IL-8 C-terminal alpha
      helix. Cleaved IL-8 reduced neutrophil activation and migration. IL-8-cleaving
      activity was found in partially purified supernatant of a necrotizing fasciitis
      isolate, and this activity was associated with an approximately 150-kDa fraction
      containing S. pyogenes cell envelope proteinase (SpyCEP). IL-8-cleaving activity
      corresponded with the presence of SpyCEP in the supernatant. Cleavage of IL-8 by
      S. pyogenes represents an unprecedented mechanism of immune evasion, effectively
      preventing IL-8 C-terminus-mediated endothelial translocation and subsequent
      recruitment of neutrophils.

PMID- 16088828
TI  - Virulence in mice of pneumococcal clonal types with known invasive disease
      potential in humans.
AB  - Streptococcus pneumoniae isolates of serotypes 1, 4, 6B, 7F, 14, and 19F
      belonging to clonal types with known invasive disease potential in humans were
      used to infect C57BL/6 and BALB/c mice. Most isolates were able to colonize the
      nasopharynx for 7 days. One serotype 19F isolate of the clonal type ST162 had
      higher bacterial numbers than other isolates and clonal types of the same
      serotype. Serotype 4 clones caused the most-severe invasive disease, whereas
      serotype 1 clones caused low-level bacteremia without disease symptoms. BALB/c
      mice were more likely than C57BL/6 mice to develop meningitis. Disease kinetics
      varied significantly between clonal types. Although most induced a robust tumor
      necrosis factor response, some isolates of serotype 1 and 7F did not, suggesting
      that invasive disease caused by different clonal types may result in different
      degrees of host response. Capsular serotype, other clonal properties, and host
      factors are important for the development of pneumococcal disease.

PMID- 16088829
TI  - The predominant variant of the Brazilian epidemic clonal complex of methicillin
      resistant Staphylococcus aureus has an enhanced ability to produce biofilm and to
      adhere to and invade airway epithelial cells.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a therapeutic
      problem. In the present study, the molecular characterization by pulsed-field gel
      electrophoresis of MRSA isolates collected from a university hospital revealed
      that the predominant variant of the Brazilian epidemic clonal complex (BECC) was
      responsible for the increase in the incidence of MRSA strains, which reached 28%
      in 1998. It was verified that this predominant variant of the BECC displayed an
      enhanced ability to produce biofilm on inert polystyrene surfaces and to adhere
      to and invade epithelial airway cells. These results indicate that MRSA strains
      belonging to the BECC have evolved advantageous properties that might play a role
      in their predominance as international nosocomial pathogens.

PMID- 16088830
TI  - Population dynamics of nasal strains of methicillin-resistant Staphylococcus
      aureus--and their relation to community-associated disease activity.
AB  - BACKGROUND: Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA)
      plays a key role in the epidemiology and pathogenesis of disease. The purpose of
      this study was to determine the characteristics and dynamics of nasal strains of
      MRSA, as well as their relation to community-associated disease activity.
      METHODS: This study is a cross-sectional survey and molecular epidemiologic
      analysis of nasal colonization by S. aureus in homeless and runaway youths, an
      underserved population at high risk for staphylococcal disease. RESULTS: Of the
      308 study participants, 27.6% carried S. aureus, and 6.2% carried MRSA. Subgroups
      of individuals with increased MRSA carriage rates were also at highest risk for
      community-associated MRSA infection; these subgroups included individuals with
      either HIV infection or AIDS, injection drug users, patients with abscesses, and
      those recently hospitalized. Multilocus sequence typing and pulsed-field gel
      electrophoresis identified 2 genotypes--ST59:P (USA1000) and ST8:S (USA300)--that
      accounted for 84.2% (16/19) of the MRSA isolates carried. The genotypes were
      distinct from nosocomial genotypes endemic in the hospital, although they
      originated from individuals with prior exposure to health care. CONCLUSIONS:
      Comparison of MRSA strains from asymptomatic carriers versus concurrently
      collected community-associated clinical strains from patients treated at local
      health-care facilities allowed for the identification of 3 population dynamics of
      nasal strains of MRSA: (1) endemic clones--for example, ST8:C and ST59:P-
      sustained asymptomatic carriage and infection over prolonged periods; (2) an
      epidemic clone, ST8:S, demonstrated enhanced capacity for rapid transmission and
      widespread infections; and (3) an outbreak clone, ST30:Z (USA1100), was highly
      infectious but exhibited poor asymptomatic transmission.

PMID- 16088831
TI  - Presence of multiple copies of the capsulation b locus in invasive Haemophilus
      influenzae type b (Hib) strains isolated from children with Hib conjugate vaccine
      failure.
AB  - Most invasive Haemophilus influenzae type b strains possess a duplication of the
      capsulation locus. Further amplification resulting in as many as 5 copies has
      been described. To verify whether amplification is involved in vaccine failure,
      the number of copies of the locus was determined by Southern blotting in 90
      strains from children with true vaccine failure (TVF) between 1993 and 1999 and
      in 139 strains from unvaccinated children (50 collected between 1993 and 1999 and
      89 collected between 1991 and 1992, before routine immunization was introduced).
      A significantly greater proportion of strains from TVFs contained multiple
      copies, compared with strains from control children (24% vs. 10%; P = .0379),
      which suggests that amplification of the capb locus may be a contributory factor
      in vaccine failure. The presence of multiple-copy strains was associated with
      disease other than meningitis.

PMID- 16088832
TI  - Vicious and virtuous circles in the dynamics of infectious disease and the
      provision of health care: gonorrhea in Britain as an example.
AB  - Prompt treatment of infectious diseases plays an important role in infection
      control. In the face of the increasing incidence of sexually transmitted
      infection, the ability of genitourinary medicine services to provide appropriate
      and timely care is reduced. To explore the relationship between capacity and
      demand for care, we developed and analyzed a mathematical model of gonorrhea
      transmission, incorporating patient flow through treatment services and
      heterogeneity in sexual risk behavior. Two equilibrium levels of infection
      incidence--"high" and "low"--exist for the same parameter values, and which of
      them occurs depends on starting conditions. At the high-incidence equilibrium,
      there is a "vicious circle" in which inadequate treatment capacity leads to many
      untreated infections, generating further high incidence and high demand and thus
      maintaining the inadequacy of services. A substantial increase in capacity is
      needed to interrupt this process and enter a "virtuous circle," in which adequate
      service provision keeps demand low, offering cost savings as well as improvements
      in health.

PMID- 16088833
TI  - Anthrax lethal toxin paralyzes neutrophil actin-based motility.
AB  - Bacillus anthracis causes high-level bacteremia, strongly suggesting paralysis of
      the innate immune system. We have examined the effects of anthrax lethal toxin
      (LT) on human neutrophil chemotaxis, a process that requires actin filament
      assembly. Polymorphonuclear neutrophils (PMNs) treated with a sublethal
      concentration of LT (50 ng/mL) for 2 h demonstrated insignificant apoptosis or
      necrosis. However, this same concentration slowed human PMN
      formylmethionylleucylphenylalanine (FMLP)-stimulated chemokinesis by >60%,
      markedly reduced polar morphology, and rendered PMNs incapable of responding to a
      chemotactic gradient. These changes were accompanied by a >50% reduction in FMLP
      induced actin filament assembly. One hour of exposure to LT failed to impair
      polarity or actin assembly, and the effects of LT were independent of mitogen
      activated protein kinase kinase 1 inhibition. We conclude that 2 h of exposure to
      LT markedly impairs PMN actin assembly, and reductions in actin filament content
      are accompanied by a profound paralysis of PMN chemotaxis.

PMID- 16088835
TI  - Evidence that interferon-gamma plays a protective role during cerebral malaria.
AB  - BACKGROUND: The pathogenic mechanisms of cerebral malaria (CM) are unclear but
      are thought to involve cytokine-mediated inflammation enhanced by parasite
      sequestration in the brain microcirculation. The role that interferon (IFN)-gamma
      could play that would enhance inflammation but also reduce parasitemia is
      unclear. METHODS: Plasma IFN-gamma concentrations were measured by enzyme-linked
      immunosorbent assay in 96 children with CM and 40 children with uncomplicated
      malaria (UM) who had been recruited from Gabriel Toure Hospital (Bamako, Mali).
      We investigated the relationship between IFN- gamma concentrations and disease by
      nonparametric analysis. Polymorphisms in IFNG were characterized by restriction
      enzyme analysis or size-determination electrophoresis. Associations between
      polymorphisms and CM were evaluated by the family-based association test on 240
      families. RESULTS: During episodes of malaria, IFN-gamma concentrations were
      lower in children with CM than in children with UM (P = .007). IFNG-183T (P =
      .009) and IFNG-183G/T (P = .013) were found to be less frequent than expected in
      children with CM. A trend toward association was also observed between
      IFNG(CA)14/(CA)14 (P = .073) and CM. The IFNG-183G/T and IFNG(CA)14/(CA)14
      genotypes were more frequent in children with UM than in children with CM (odds
      ratio, 0.30 and 0.34, respectively). CONCLUSIONS: The low plasma IFN- gamma
      concentrations in children with CM and the associations between a reduced risk of
      CM and (1) the IFNG-183T allele (which increases gene transcription) and (2) the
      IFNG-183G/T genotype are consistent with the concept that IFN-gamma protects
      against CM.

PMID- 16088834
TI  - A randomized comparison of artesunate-atovaquone-proguanil versus quinine in
      treatment for uncomplicated falciparum malaria during pregnancy.
AB  - BACKGROUND: There is no safe, practical, and effective treatment for pregnant
      women infected with multidrug-resistant Plasmodium falciparum. METHODS: We
      recruited pregnant Karen women in the second or third trimesters of pregnancy who
      had uncomplicated falciparum malaria for a randomized, open-label trial with a
      restricted sequential trial design of 7 days of supervised quinine (SQ7) versus 3
      days of artesunate-atovaquone-proguanil (AAP). RESULTS: Eight-one pregnant women
      entered the study between December 2001 and July 2003; 42 were treated with SQ7
      and 39 were treated with AAP. Fever, parasite clearance, and duration of anemia
      were significantly better with AAP; the treatment failure rate was 7 times lower
      (5% [2/39] vs. 37% [15/41]; relative risk, 7.1 [95% confidence interval, 1.7
      29.2]; P = .001). There were no significant differences in birth weight, duration
      of gestation, or congenital abnormality rates in newborns or in growth and
      developmental parameters of infants monitored for 1 year. CONCLUSION: AAP is a
      well-tolerated, effective, practical, but expensive treatment for multidrug
      resistant falciparum malaria during the second or third trimesters of pregnancy.
      Despite the small number of subjects, our results add to the growing body of
      evidence that AAP is safe for the mother and the fetus.

PMID- 16088836
TI  - Antibodies to rhoptry-associated membrane antigen predict resistance to
      Plasmodium falciparum.
AB  - Previously, we collected plasma from 143 male volunteers residing in an area of
      western Kenya where Plasmodium falciparum is holoendemic. Volunteers were cured
      of current malaria infection by use of drugs, blood was collected 2 weeks after
      treatment, and blood films were collected weekly for 18 weeks. We identified and
      pooled plasma from the 10 most resistant individuals (RP) and the 7 most
      susceptible individuals (SP) and used these pools in a differential screen of a
      P. falciparum cDNA expression library. We screened 550,000 clones and identified
      7 clones that were uniquely recognized by RP but not by SP. Two clones encoded a
      C-terminal region polypeptide from rhoptry-associated membrane antigen (RAMA-pr),
      a recently described RAMA. We measured anti-RAMA-pr antibody levels in plasma
      obtained 2 weeks after treatment. Individuals with detectable immunoglobulin G1
      anti-RAMA-pr (n = 24) had fewer positive blood films (odds ratio, 1.7 [95%
      confidence interval, 1.21-2.44]; P < .003), 43% lower density of parasitemia (P <
      .02), and prolonged time to reinfection (P < .0027), compared with individuals
      without detectable antibody levels (n = 115), after known determinants of
      resistance were accounted for. In summary, RAMA-pr is a rationally identified
      vaccine candidate that is preferentially recognized by antibodies produced by
      humans with a high level of naturally acquired resistance to P. falciparum
      infection.

PMID- 16088837
TI  - Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and
      its effect on the performance of PfHRP2-based rapid diagnostic tests.
AB  - Rising costs of antimalarial agents are increasing the demand for accurate
      diagnosis of malaria. Rapid diagnostic tests (RDTs) offer great potential to
      improve the diagnosis of malaria, particularly in remote areas. Many RDTs are
      based on the detection of Plasmodium falciparum histidine-rich protein (PfHRP) 2,
      but reports from field tests have questioned their sensitivity and reliability.
      We hypothesize that the variability in the results of PfHRP2-based RDTs is
      related to the variability in the target antigen. We tested this hypothesis by
      examining the genetic diversity of PfHRP2, which includes numerous amino acid
      repeats, in 75 P. falciparum lines and isolates originating from 19 countries and
      testing a subset of parasites by use of 2 PfHRP2-based RDTs. We observed
      extensive diversity in PfHRP2 sequences, both within and between countries.
      Logistic regression analysis indicated that 2 types of repeats were predictive of
      RDT detection sensitivity (87.5% accuracy), with predictions suggesting that only
      84% of P. falciparum parasites in the Asia-Pacific region are likely to be
      detected at densities < or = 250 parasites/microL. Our data also indicated that
      PfHRP3 may play a role in the performance of PfHRP2-based RDTs. These findings
      provide an alternative explanation for the variable sensitivity in field tests of
      malaria RDTs that is not due to the quality of the RDTs.

PMID- 16088838
TI  - An anti-Chitinase malaria transmission-blocking single-chain antibody as an
      effector molecule for creating a Plasmodium falciparum-refractory mosquito.
AB  - Indirect evidence has suggested the existence of a second chitinase gene, PgCHT2,
      in the avian malaria parasite Plasmodium gallinaceum. We have now identified
      PgCHT2 as the orthologue of the P. falciparum chitinase gene PfCHT1, a malaria
      transmission-blocking target. Computational phylogenetic evidence and biochemical
      and cell biological functional data support the hypothesis that an avian-related
      Plasmodium species was the ancestor of both P. falciparum and P. reichenowi, and
      this single lineage gave rise to another lineage of malaria parasites, including
      P. vivax, P. knowlesi, P. berghei, P. yoelii, and P. chabaudi. A recombinant
      PfCHT1/PgCHT2-neutralizing single-chain antibody significantly reduced P.
      falciparum and P. gallinaceum parasite transmission to mosquitoes. This single
      chain antibody is the first anti-P. falciparum effector molecule to be validated
      for making a malaria transmission-refractory transgenic Anopheles species
      mosquito. P. gallinaceum is a relevant animal model that facilitates a
      mechanistic understanding of P. falciparum invasion of the mosquito midgut.

PMID- 16088839
TI  - Prevalence of clinical isolates of Cryptococcus gattii serotype C among patients
      with AIDS in Sub-Saharan Africa.
AB  - Cryptococcus gattii is a group of exogenous, neurotropic yeasts that possess the
      capsular serotype B or C. Isolates of serotype C are extremely rare and, until
      recently, were known to infect only immunocompetent individuals. We genotyped 176
      isolates of Cryptococcus from patients in sub-Saharan Africa who had AIDS; 22
      (13.7%) of 161 isolates from Botswana and 2 (13.3%) of 15 isolates from Malawi
      were C. gattii serotype C strains. All of these serotype C strains belong to the
      rare VGIV genotype, possess the MAT alpha mating-type allele, and exhibit little
      genetic diversity.

PMID- 16088840
TI  - A simple approach for estimating gene expression in Candida albicans directly
      from a systemic infection site.
AB  - Gene expression analysis after the host-pathogen interaction is revolutionizing
      our understanding of the host response to infection. Numerous studies have
      utilized microarray analysis to follow host cell transcriptome alterations in
      response to interactions with infectious pathogens. However, similar analyses of
      pathogen transcriptional adaptation at the infection site have been limited.
      Understanding the nature of this interaction from the pathogen perspective at
      different sites and stages of infection is central to strategies for development
      of new anti-infective therapies. Toward this end, we developed a protocol to
      analyze changes in gene expression for a eukaryotic pathogen, Candida albicans,
      during systemic infection in mice. The experimental approach takes advantage of
      the resistance of the cell wall of many fungal pathogens to cell lysis, relative
      to mammalian cells. After lysis of mammalian cells, the tissue mixture containing
      fungal cells is depleted of mammalian RNA by centrifugation, followed by
      enzymatic digestion. RNA-digesting enzymes are then inhibited before eukaryotic
      cell lysis and RNA isolation. The protocol provides a reproducible quantity of
      RNA based on pathogen cell number. The quality of the RNA allowed reliable
      downstream transcriptional analysis using reverse-transcription polymerase chain
      reaction and microarrays. The in vivo gene expression data confirmed involvement
      of several putative pathogenesis genes. More importantly, the results provided a
      wealth of biologically interesting hypotheses to direct future investigation.

PMID- 16088841
TI  - Coculture of THP-1 human mononuclear cells with Candida albicans results in
      pronounced changes in host gene expression.
AB  - BACKGROUND: The host's first line of defense against bloodstream infection with
      Candida albicans involves the recognition and clearance of the fungus by
      neutrophils and monocytes/macrophages. The purpose of the present study was to
      examine changes in the monocytic cell gene-expression profile in response to C.
      albicans stimulation. METHODS: RNA was isolated from THP-1 cells 3 h after
      coculture with live C. albicans SC5314 cells. After hybridization to microarrays,
      genes differentially expressed by at least 2.0-fold were included in the final
      data set. RESULTS: As expected, TNFA, IL8, CD83, MIP1A, and MIP1B were among the
      genes up-regulated. This was confirmed by real-time reverse-transcriptase
      polymerase chain reaction (RT-PCR), fluorescence-activated cell sorting analysis,
      and enzyme-linked immunosorbent assay. Furthermore, RGS1, RGS2, RGS16, DSCR1,
      GROB, EGR3, FLT4, and TNFAIP6 were also up-regulated in response to C. albicans,
      whereas CCR2 and NCF2 were among the genes down-regulated in response to C.
      albicans. Differential expression of selected genes was confirmed at several time
      points by real-time RT-PCR. CONCLUSIONS: This study defines the gene expression
      profile of an early response of human mononuclear cells to C. albicans and
      identifies genes not previously known to be responsive to this pathogen.

PMID- 16088842
TI  - Rotavirus antigenemia in patients with acute gastroenteritis.
AB  - Although rotavirus infections are generally considered to be confined to the
      intestine, recent reports suggest that extraintestinal disease occurs. We studied
      whether rotavirus infection was associated with antigenemia during a major
      outbreak of gastroenteritis in the Kingston metropolitan area, during July-August
      2003. Rotavirus antigen was identified in 30 of 70 acute-phase serum samples
      (including from 2 deceased individuals) but in only 1 of 53 control samples.
      Serum antigen levels were inversely associated with time since symptom onset and
      were directly associated with antigen levels in stool (P = .02). Serum antigen
      levels were significantly elevated during primary infections (acute-phase serum
      immunoglobulin G [IgG] titers, <25), compared with those in subsequent infections
      (acute-phase serum IgG titers, > or = 25) (P = .02). Antigenemia was common in
      this outbreak and might provide a mechanism to help explain rare but well
      documented reports of findings of extraintestinal rotavirus. In situations in
      which stool samples are not readily available (i.e., patients with severe
      dehydration or those recently recovered or deceased), serum testing by enzyme
      immunoassay offers a new and practical diagnostic tool.

PMID- 16088843
TI  - Modulation of vaccine-induced immune responses to hepatitis C virus in rhesus
      macaques by altering priming before adenovirus boosting.
AB  - BACKGROUND: Preventive and therapeutic vaccine strategies aimed at controlling
      hepatitis C virus (HCV) infection should mimic the immune responses observed in
      patients who control or clear HCV, specifically T helper (Th) type 1 and CD8+
      cell responses to multiple antigens, including nonstructural protein (NS) 3.
      Given the experience with human immunodeficiency virus, the best candidates for
      this are based on DNA prime, pox, or adenovirus boost regimens. METHODS: In
      rhesus macaques, we compared NS3-expressing DNA prime and adenovirus boost
      strategy with 2 alternative priming approaches aimed at modifying Th1 and CD8+
      responses: DNA adjuvanted with interleukin (IL)-2- and -12-encoding plasmids or
      Semliki Forest virus (SFV). RESULTS: All prime-boost regimens elicited NS3
      specific B and T cell responses in rhesus macaques, including CD8+ responses. SFV
      priming induced higher lymphoproliferation and longer Th1 memory responses. The
      use of IL-2- and IL-12-expressing vectors resulted in reduced Th2 and antibody
      responses, which led to increased Th1 skewing but not to an increase in the
      magnitude of the IFN- gamma and CD8+ responses. CONCLUSIONS: All strategies
      induced Th1 cellular responses to HCV NS3, with fine modulations depending on the
      different priming approaches. When they are developed for more HCV antigens,
      these strategies could be beneficial in therapeutic vaccine approaches.

PMID- 16088844
TI  - Thermal stability of hepatitis E virus.
AB  - The thermal stability of virulent hepatitis E virus (HEV) and hepatitis A virus
      (HAV) was compared. Fecal suspensions of virus were heated to temperatures
      between 45 degrees C and 70 degrees C, and residual infectivity was determined in
      a cell culture system that was permissive for both viruses. Although HEV was less
      stable than was HAV, some HEV would most likely survive the internal temperatures
      of rare-cooked meat.

PMID- 16088845
TI  - Highly bovine spongiform encephalopathy-sensitive transgenic mice confirm the
      essential restriction of infectivity to the nervous system in clinically diseased
      cattle.
AB  - Transgenic mice expressing bovine prion protein (PrP)(C) (Tgbov XV mice) display
      remarkably shorter incubation times for cattle-derived bovine spongiform
      encephalopathy (BSE) infectivity than do nontransgenic mice. To verify that this
      phenomenon reflects increased sensitivity, we challenged Tgbov XV mice and
      conventional RIII mice with a BSE brain-stem homogenate of known infectivity
      titer in cattle. An end-point titration experiment in Tgbov XV mice revealed
      their superior sensitivity, which exceeded that of RIII mice by at least 10,000
      fold and even that of cattle by approximately10-fold. Moreover, Tgbov XV mice
      were challenged with various tissues from cattle with end-stage clinical BSE, and
      infectivity was found only in the central and peripheral nervous system and not
      in lymphatic tissues; the only exception was the Peyer's patches of the distal
      ileum, which most likely are the site of entry for BSE infectivity. These results
      provide further indication that the pathogenesis of BSE in cattle is
      fundamentally different from that in sheep and mice, due to an exclusive
      intraneuronal spread of infectivity from the gut to the central nervous system.

PMID- 16088846
TI  - Preventing end stage renal disease in diabetic patients--genetic aspect (part I).
AB  - Diabetic nephropathy is a major cause of diabetes- related morbidity and
      mortality; however the clinical course of the disease and the renal prognosis is
      highly variable among individuals. The current review will discuss the genetic
      influence on the development of end stage renal disease (ESRD) in diabetic
      patients and potential improvements to the current treatment strategy to slow the
      loss of kidney function in these patients. In this first part, the growing
      evidence that glucose-induced activation of the intra-renal and systemic renin
      angiotensin systems plays an essential role in processes leading to destruction
      of renal function is summarised. Genetic variations, especially the angiotensin
      converting enzyme (ACE)/ID polymorphisms in the gene coding for ACE, are involved
      in activation of the renin-angiotensin system and seem to influence the clinical
      course of diabetic nephropathy during treatment with ACE inhibitors. In addition,
      this polymorphism may interact with other polymorphisms within the renin
      angiotensin system, leading to high risk of ESRD. As new genetic approaches and
      methods develop, further understanding of diabetic nephropathy will evolve and
      genotyping will help prevent ESRD in diabetic patients.

PMID- 16088847
TI  - Molecular-specific effects of angiotensin II antagonists: clinical relevance to
      treating hypertension?
AB  - Angiotensin II receptor blockers (ARBs) may produce a number of molecule-specific
      effects that appear to be independent of interaction with the angiotensin II type
      1 (AT1)-receptor. These include antagonism of the thromboxane A2 receptor,
      inhibition of platelet aggregation, induction of peroxisome proliferator-
      activated receptor gamma (PPARgamma) activity, and reduction of serum uric acid
      levels. However, definitive evidence is lacking that these molecule-specific
      effects give rise to a therapeutic advantage of one ARB over another. Currently,
      the possibility of a link between a molecule-specific effect of an ARB and an
      improvement in clinical outcomes is best illustrated by a reduction in serum uric
      acid levels with losartan. Data from Losartan Intervention For Endpoint reduction
      in hypertension (LIFE) study suggest a treatment-induced decrease in serum uric
      acid may contribute to the treatment benefit of a losartan-based versus atenolol
      based therapy on the composite endpoint (death, myocardial infarction, or
      stroke). This finding should prompt further studies to investigate the long-term
      cardioprotective benefits issue of reducing hyperuricaemia in hypertensive
      patients.

PMID- 16088848
TI  - The DIabetic REtinopathy Candesartan Trials (DIRECT) Programme: baseline
      characteristics.
AB  - Renin-angiotensin system blockade has been shown to be superior to other
      antihypertensive therapy in slowing progression of renal disease in diabetic
      patients, but questions remain regarding diabetic retinopathy. The primary
      objective of the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme is to
      examine primary (incidence) and secondary (progression) prevention of diabetic
      retinopathy when blocking angiotensin II type 1-receptors with candesartan in
      normoalbuminuric, normotensive Type 1 diabetic patients, and secondary prevention
      only in normoalbuminuric, normotensive or treated hypertensive Type 2 diabetic
      patients. The secondary objectives include examining the effect of candesartan
      treatment on urinary albumin excretion rate (UAER) in each of the three studies
      and to examine the incidence of proliferative retinopathy in all three
      populations combined. Standardised investigations for patients at enrolment
      include blood pressure measurement, analysis of HbA1C and serum lipids, and a
      detailed ophthalmological examination. Retinopathy and UAER outcomes are assessed
      yearly. Retinopathy is graded centrally, based on seven-field stereo photographs
      using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol.
      Randomisation was performed when the results of retinal gradings were available,
      and treatment with 16 mg candesartan cilexetil or matching placebo was initiated;
      the dose was increased to 32 mg after one month. Calculations of UAER are based
      on two timed overnight urine collections. A sample size re-assessment was carried
      out when approximately 70% of the patients had been randomised in the DIRECT
      Programme to ensure the results to be conclusive. In total, 5,231 patients were
      randomised in the DIRECT Programme in 30 countries. One thousand, four hundred
      and twenty one and 1,905 patients are evaluated in the primary and secondary
      prevention studies in Type 1 diabetes, respectively and 1,905 patients in the
      secondary prevention study in Type 2 diabetes. HbA1C showed mean values of 8.1,
      8.5 and 8.2% for the Type 1 primary, Type 1 secondary and Type 2 secondary
      prevention studies, respectively. In the Type 1 secondary prevention study, 49%
      of the patients had mild nonproliferative retinopathy (level 20) in at least one
      eye, and 9% had moderate-moderately severe non-proliferative retinopathy (level
      43-47). In Type 2 patients, 17% had level 43-47 and the remainder less severe
      retinopathy.

PMID- 16088849
TI  - Additive effects of endothelial progenitor cells combined with ACE inhibition and
      beta-blockade on left ventricular function following acute myocardial infarction.
AB  - Animal studies have demonstrated the efficacy of endothelial progenitor cells
      (EPCs) in preventing left ventricular (LV) remodelling following myocardial
      infarction (MI). Preliminary human studies are underway, yet no studies have
      demonstrated efficacy in combination with standard medical therapy, i.e.
      angiotensin-converting enzyme (ACE) inhibitors and beta-blockers. Nude rats
      underwent left anterior descending coronary artery ligation to induce MI. Animals
      were randomised to receive no treatment (MI, n = 5), quinapril 200 mg/L +
      metoprolol 2 g/L (ACE/BB, n = 5), two million EPCs intravenously (EPC, n = 5)or
      both (ACE/BB + EPC [n = 5]), then sacrificed after two weeks treatment. ACE/BB
      resulted in a 75% reduction in fibrosis in the region remote from the MI (p <
      0.05), but EPC therapy had little effect here. Conversely, EPC therapy induced
      neovascularisation at the peri-infarct rim, thereby preventing peri-infarct
      apoptosis by 81% (p < 0.05). Acting via different but complementary mechanisms,
      the combination of ACE/BB + EPCs resulted in a greater overall improvement in LV
      function on echocardiography than either therapy alone. Clinical trials using
      stem cell therapy in conjunction with standard medical treatment are warranted.

PMID- 16088850
TI  - Renin-angiotensin system gene polymorphisms and premature coronary heart disease.
AB  - INTRODUCTION: Experimental and clinical studies demonstrated that the renin
      angiotensin system (RAS) affects the pathogenesis of atherosclerosis and
      prognosis of coronary heart disease (CHD). The aim of this study was to
      investigate the genotype distribution and the allele frequencies of three RAS
      genes polymorphisms and their effects on premature CHD in a Turkish population.
      MATERIALS AND METHODS: One-hundred and fifteen Turkish patients with premature
      CHD and 128 controls were included into the study. Angiotensin-converting enzyme
      (ACE), angiotensin II type 1 (AT1) receptor and angiotensinogen (AGT) gene
      polymorphisms were analysed by polymerase chain reaction (PCR) and restriction
      fragment length polymorphism (RFLP). RESULTS: The patients group showed an
      increased frequency of the ACE D allele compared with controls (65% vs. 35%, p =
      0.0001). There was a significant association between the DD genotype and
      premature CHD (ACE DD vs. ID and II; odds ratio [OR] = 2.82 [CI 95% 1.33 2.91, p
      = 0.002]). Also, we observed increased premature CHD risk associated with higher
      frequencies of the AGT MM genotype in patients when compared with controls (AGT
      MM vs. TT and MT, OR = 1.92 [CI 95% 1.11-3.33, p = 0.018]). We found a
      significant association between AT1-receptor AA genotype and decreased risk of
      premature CHD (AT1R AA vs. AC and CC, OR = 0.57[CI 95% 0.34-0.95, p = 0.03]).
      CONCLUSIONS: We demonstrated that increased premature CHD risk is associated with
      higher frequencies of the ACE DD and AGT MM genotypes. These findings indicate a
      synergistic contribution of ACE DD and AGT MM polymorphisms to the development of
      premature CHD. Also, our results suggest that family history, smoking, diabetes,
      hypertension, obesity and ACE DD genotype were independent risk factors for
      premature CHD.

PMID- 16088851
TI  - Angiotensin II receptor blockade and ventricular remodelling.
AB  - Cardiac remodelling is the expression of molecular, cellular and interstitial
      changes in response to cardiac injury, manifesting as adverse alterations in the
      size, shape and function of the ventricle. Several clinical studies have
      documented significant elevations in the levels of renin, angiotensin II (Ang II)
      and aldosterone attending acute myocardial infarction and/or congestive heart
      failure. Similar to catecholamines, markedly elevated activity of the renin
      angiotensin-aldosterone system (RAAS) is associated with poor prognosis. The
      effects of Ang II upon cardiac tissue are related to two primary receptors, Ang
      II type 1 (AT1) and Ang II type 2 (AT2). The AT1-receptor appears to mediate many
      of the deleterious effects of chronic RAAS activity, while the AT2-receptor is
      increasingly shown to have potential cardioprotective effects. Attenuating the
      deleterious effects of sustained Ang II stimulation can be achieved by direct
      inhibition of angiotensin- converting enzyme (ACE) and/or direct antagonism of AT
      receptors. ACE inhibition reduces left ventricular (LV) volumes, retards the
      progression of LV dilatation and hypertrophy and increases systolic function in
      systolic dysfunction. By blocking at the receptor level, Ang II receptor blockers
      (ARBs) provide an alternative and more direct approach to inhibiting the effects
      of Ang II; however, data relating to their effects upon ventricular remodelling,
      whether used in isolation or in combination with ACE inhibitors (ACE-Is), are
      less convincing. Data arising from several recent clinical trials suggest that
      simultaneous use of ACE-Is and ARBs maybe of more benefit in attenuating
      ventricular remodelling than either agent alone.

PMID- 16088852
TI  - A noninvasive transfer system for polarized renal tubule epithelial cell sheets
      using temperature-responsive culture dishes.
AB  - We used temperature-responsive culture dishes onto which the temperature
      responsive polymer, poly(Nisopropylacrylamide), was covalently grafted for tissue
      engineering. Confluent cells harvested as intact sheets from these surfaces by
      simple temperature reduction can be transferred to various surfaces including
      additional culture dishes, other cell sheets, and tissues. In order to examine
      the maintenance of cell polarity, Madin-Darby canine kidney cells and human
      primary renal proximal tubule epithelial cells which had developed apical-basal
      cell polarity in culture, were subjected to cell sheet transfer. This functional
      and structural cell polarity, which is susceptible to treatment with trypsin, was
      examined by immunohistochemistry and transmission electron microscopy. Using our
      cell-sheet method, the noninvasive transfer of these cell sheets retaining
      typical distributions of Na+/K+-ATPase, GLUT-1, SGLT-1, aquaporin-1, neutral
      endopeptidase and dipeptidylendopeptidase IV, could be achieved. The transferred
      cell sheets also developed numerous microvilli and tight junctions at the apical
      and lateral membranes, respectively. For biochemical analysis, immunoblotting of
      occludin, a transmembrane protein that composes tight junctions, was conducted
      and results confirmed that occludin remained intact after cell sheet transfer.
      This two-dimensional cell sheet manipulation method promises to be useful for
      tissue engineering as well as in the investigation of epithelial cell polarity.

PMID- 16088853
TI  - New beginnings.

PMID- 16088854
TI  - To tame a volcano: patients with borderline personality disorder and their
      perceptions of suffering.
AB  - The aim of the study was to investigate life situations, suffering, and
      perceptions of encounter with psychiatric care among 10 patients with borderline
      personality disorder. The results are based on a hermeneutic interpretation of
      narrative interviews in addition to biographical material (diary excerpts and
      poems). The interpretation revealed three comprehensive theme areas: life on the
      edge , the struggle for health and dignity-a balance act on a slack wire over a
      volcano , and the good and the bad act of psychiatric care in the drama of
      suffering . These theme areas form a movement back and forth-from despair and
      unendurable suffering to struggle for health and dignity and a life worth living.
      Common beliefs regarding these patients among personnel and implications for
      psychiatric care are discussed in relation to the results.

PMID- 16088855
TI  - Perilous work: nurses' experiences in psychiatric units with high risks of
      assault.
AB  - Psychiatric facilities struggle to maintain therapeutic environments made
      increasingly difficult by severe nursing shortages. Related safety concerns
      prompted a phenomenological inquiry about nurses' experiences working in
      environments with high risks of assault. Ten registered nurses participated in
      open-ended interviews. Analysis of interview transcripts generated four
      categories and 13 subcategories subsumed under the primary construct of "perilous
      work," providing the frame for the exhaustive description and essential structure
      of participants' lived experiences. Outcomes suggest that serious work-related
      hazards exist and provide insight into possible remedies and a springboard for
      follow-up studies.

PMID- 16088856
TI  - Group therapy for survivors of childhood sexual abuse who have chronic mental
      illness.
AB  - Medication and supportive services are usually the approaches used to treat women
      with chronic mental illness (CMI). The goal of this study was to evaluate the
      outcomes of group therapy for women with CMI in comparison with those for women
      without CMI, all of whom experienced childhood sexual abuse. The sample ( N=121)
      consisted of women, all of whom were sexually abused as children. The results
      indicated that abused women with CMI had improved self-esteem and decreased
      symptom scores at the same rate as abused women without CMI. It was suggested
      that nurses can play an essential role in their practice with this population.

PMID- 16088857
TI  - Nursing students' attitudes toward mental health nursing and consumers:
      psychometric properties of a self-report scale.
AB  - There is a paucity of measures suitable for assessing the impact of educational
      and clinical placement strategies on nursing students' career preferences and
      attitudes toward mental health nursing and consumers of mental health services.
      Information derived from such scales could be used to improve existing
      recruitment strategies to this specialty area and identify misperceptions held by
      individuals joining the health care workforce. This article details the
      psychometric properties of a self-report scale designed to assess (1)
      preparedness for the mental health field, (2) attitudes toward mental illness and
      consumers of mental health services, and (3) attitudes toward mental health
      nursing, including career preferences. Results are based on data from a large
      Victorian study that explored the attitudes of 802 nursing students before their
      clinical placement in the mental health field. Principal components analysis with
      oblique rotation was used to identify the number and composition of components
      composing the newly developed scale. Results indicated seven components composed
      of relatively homogenous items; most items were good to excellent measures of
      each component. Cronbach alpha values indicated acceptable internal consistency
      of items composing four of the suggested components. Overall, findings indicated
      that the self-report scale is a useful instrument with acceptable psychometric
      properties. Descriptive and correlational analyses emphasized the importance of
      educational preparation preplacement and highlighted the potential for
      educational strategies to improve recruitment via improved attitudes and
      preparedness.

PMID- 16088858
TI  - Self-care symptom management strategies for auditory hallucinations among
      inpatients with schizophrenia at a Veterans' Hospital in Taiwan.
AB  - The purpose of this study was to explore self-care management strategies for
      auditory hallucinations (AHs) among inpatients with schizophrenia. Self-report
      and semistructured questionnaires were used to identify 36 self-management
      strategies of 200 inpatients with schizophrenia living at a veterans' hospital in
      Taiwan. The most commonly used management category was behavioral change and the
      most commonly used strategy was ignoring the AHs. The most common resource for
      strategies was self-learning. These results can help broaden health care
      providers' understanding about self-care management strategies for coping with
      AHs among inpatients with schizophrenia. Developing a manual containing selected
      self-care strategies and incorporating those strategies into cognitive-behavioral
      psychotherapy could be useful and beneficial to patients experiencing AHs.

PMID- 16088859
TI  - Comment on "Paying the price: the psychiatric cost of war.

PMID- 16088861
TI  - Non-empirical calculations of NMR indirect spin-spin coupling constants. Part 13:
      configurational assignment of aminosulfonylamidines.
AB  - Carbon-carbon coupling constants have been experimentally measured using the
      INADEQUATE pulse sequence in the series of N-[1,2-bis(dialkylamino)-2
      arylethylidene]arylsulfonamides obtained from N-(1-aryl-2,2,2
      trichloroethyl)amides of arylsulfonic acids. Comparison of the experimental
      J(C,C) in this series with those calculated at the SOPPA (Second-Order
      Polarization Propagator Approach) level in the model aminosulfonylamidine
      provided an unambiguous assignment at the C=N bond of the eight-title
      aminosulfonylamidines to E-configuration, while the unknown J(C,C) couplings in
      their inaccessible diverse Z isomers have been predicted with high reliability.
      The established marked difference between J(C,C) of the corresponding carbon
      carbon bonds in cis and trans orientations to the nitrogen lone pair in
      aminosulfonylamidines provides a powerful tool in the configurational assignment
      at the C=N bond in a wide series of the related systems containing the C=N-SO2R
      moiety.

PMID- 16088862
TI  - Second trimester ultrasound prenasal thickness combined with nasal bone length: a
      new method of Down syndrome screening.
AB  - OBJECTIVE: To evaluate ultrasound prenasal thickness (PT) as a way of enhancing
      the Down syndrome (DS) screening performance of second-trimester nasal bone (NB)
      length measurement. METHODS: Twenty-one DS and 500 normal fetuses were scanned at
      14-27 weeks' gestation. The affected karyotype was known to the person performing
      the scan. Both PT and NB were measured in a mid-sagittal position and results
      were expressed in multiples of the normal gestation-specific median (MoM).
      Gaussian modelling was used to predict the performance of routine screening.
      RESULTS: Among DS fetuses, the PT median was 1.35 MoM, a highly statistically
      significant increase compared with the unaffected pregnancies (p < 0.0001,
      Wilcoxon Rank Sum Test, two-tailed). The NB median was 0.87 MoM (p < 0.0005) and
      the ratio PT/NB median was 1.51 MoM (p < 0.0001). In the normal fetuses, the two
      markers were positively correlated (0.25, p < 0.0001), whereas in the DS fetuses
      there was a non-significant negative correlation (-0.24, p = 0.33). For a 5%
      false-positive rate, the model predicted detection rate was 70% for PT and NB
      compared with 43% for NB alone. CONCLUSION: In the second trimester, PT is
      increased on average in DS fetuses. Combining PT and NB measurement could yield a
      higher screening detection rate than NB alone. Confirmation of our findings in a
      series of women scanned before the karyotype was known is needed before the
      method can be clinically implemented.

PMID- 16088863
TI  - Prenatal diagnosis in a family with X-linked hydrocephalus.
AB  - The neural cell adhesion molecule L1 is a transmembrane glycoprotein belonging to
      the immunoglobulin superfamily of cell adhesion molecules (CAMs). Its expression
      is essential during embryonic development of the nervous system and it is
      involved in cognitive function and memory. Mutations in the L1CAM gene are
      responsible for four related L1 disorders; X-linked hydrocephalus/HSAS
      (Hydrocephalus as a result of Stenosis of the Aqueduct of Sylvius), MASA (Mental
      retardation, Aphasia, Shuffling gait, and Adducted thumbs) syndrome, X-linked
      complicated spastic paraplegia type I (SPG1) and X-linked Agenesis of the Corpus
      Callosum (ACC). These four disorders represent a clinical spectrum that varies
      both between and within families. The main clinical features of this spectrum are
      Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic
      paraplegia and Hydrocephalus (CRASH syndrome). Since there is no biochemically
      assayed disease marker, molecular analysis of the L1CAM gene is the only means of
      confirming a clinical diagnosis. Most L1CAM mutations reported to date are point
      mutations (missense, nonsense, splice site) and only a few patients with larger
      rearrangements have been documented. We have characterised a rare intragenic
      deletion of the L1CAM gene in a sample of DNA extracted from a chorionic villus
      biopsy (CVB) performed at 12 weeks' gestation. =

PMID- 16088864
TI  - The influence of maternal insulin-dependent diabetes on fetal nuchal translucency
      thickness and first-trimester maternal serum biochemical markers of aneuploidy.
AB  - OBJECTIVE: To evaluate the influence of maternal insulin dependent diabetes
      mellitus (IDDM) on maternal serum free beta-hCG, PAPP-A and fetal nuchal
      translucency (NT), thickness at 11 to 13(+6) weeks of gestation in a large cohort
      of women screened prospectively for chromosomal anomalies. METHODS: Information
      on maternal IDDM status, maternal serum biochemical marker levels and fetal NT
      were collected from the prenatal screening computer records in two first
      trimester screening centres. In total the control group included 33 301
      pregnancies of which 16 366 had NT and maternal serum biochemistry results and 16
      305 with NT only. The IDDM group included 195 pregnancies of which 79 had NT and
      maternal serum biochemistry results and 127 with NT only. The median maternal
      weight corrected free beta-hCG and PAPP-A, expressed as multiple of the median
      (MoM), and fetal NT, expressed as delta values, in the IDDM and non-IDDM groups
      were compared. RESULTS: There were no significant differences between the IDDM
      and non-IDDM groups in median maternal weight corrected free beta-hCG (IDDM 0.87
      MoM, 95% Confidence Interval 0.75 to 1.16 MoM, non-IDDM 1.00 MoM), median
      maternal weight corrected PAPP-A (IDDM 1.02 MoM, 95% Confidence Interval 0.83 to
      1.05 MoM, non-IDDM 1.01 MoM), or mean delta NT (IDDM 0.0358 mm, non-IDDM 0.0002
      mm). CONCLUSIONS: In pregnancies with maternal IDDM, first-trimester screening
      for chromosomal defects does not require adjustments for the measured fetal NT.
      However, more data are required before the possible reduction in maternal serum
      free beta-hCG and the reduction of PAPP-A suggested by the published world series
      can be considered sufficiently important to take into account in the calculation
      of risks for chromosomal defects.

PMID- 16088865
TI  - Array comparative genomic hybridization profiling of first-trimester spontaneous
      abortions that fail to grow in vitro.
AB  - OBJECTIVES: Cytogenetic analysis of spontaneous abortion samples can be limited
      by culture failure. Failure to grow in vitro has traditionally been suspected to
      be due to in vivo death of tissue associated with spontaneous abortion (SAB) or
      simply technical factors of growth in culture. METHOD: We used array comparative
      genomic hybridization (array CGH) to investigate chromosomal imbalances in
      products of conception that failed to grow in vitro. RESULTS: Our data on 26
      cases of SABs that failed to grow in culture are compared and contrasted with
      published data on cytogenetic findings following in vitro culture. The results
      revealed abnormalities uncommonly seen by classic cytogenetic methods. These
      abnormalities include high rates of double aneuploidy and autosomal monosomy. The
      data taken together suggest that classic cytogenetics of spontaneous abortion may
      yield normal karyotypes or selected abnormal karyotypes that permit cell
      proliferation in vitro while Array CGH detects other abnormalities. CONCLUSION:
      Array CGH is becoming an important clinical assay for unbalanced chromosome
      abnormalities whether cells grow in culture or not and in cases of analysis on
      one or few cells.

PMID- 16088866
TI  - Trisomy 2 due to a 3:1 segregation in an abortion studied by QF-PCR and CGH.
AB  - Balanced reciprocal translocation is one of the known causes of recurrent
      spontaneous abortions. Cytogenetic studies of unbalanced miscarriages are
      difficult due to the growth failure of early loss and usually macerated
      abortions. We present a molecular study of an abortion in which the father
      carries a balanced reciprocal translocation t(2;17)(q32.1;q24.3) using QF-PCR and
      CGH techniques. DNA analysis showed the presence of a trisomy 2 due to a 3:1
      interchange segregation. Recombinant events could also be investigated by
      comparing DNA samples from the family. We propose QF-PCR in addition to CGH as an
      efficient diagnostic method to improve our knowledge of unbalanced offspring in
      balanced translocation carriers.

PMID- 16088867
TI  - Interstitial deletion del(10)(q25.2q25.3 approximately 26.11)--case report and
      review of the literature.
AB  - OBJECTIVES: To present the clinical, cytogenetic, and molecular cytogenetic
      findings of prenatally diagnosed interstitial deletion 10q25.2-q26.1. The
      majority of distal 10q deletions are pure terminal deletions with breakpoints in
      10q25 and 10q26. Only four patients have been described so far with interstitial
      deletions involving bands 10q25.2-q26.1. METHODS: Postmortem physical examination
      and autopsy of the foetus after medically terminated pregnancy. GTG-banding,
      reverse painting, and FISH analysis with BAC clones on amniocyte metaphases were
      performed to determine the extent of the deletion. RESULTS: At 20 weeks the
      eutrophic female foetus showed pronounced microretrogeny and hypertelorism,
      clubfeet as well as minor internal anomalies like pancreas anulare, atypically
      lobed liver, and missing choleocystis. Cardiac anomalies were not observed and
      the genitalia were of a normal female. The deletion encompasses 6-Mb and is
      associated with hemizygosity for 30 genes, including the genes for beta-tectorin,
      the beta-1 adrenergic receptor, and the alpha-2A adrenergic receptor. CONCLUSION:
      An interstitial deletion del(10)(q25.2q25.3 approximately 26.11) was confirmed by
      FISH with mapped BAC clones. Clinical and molecular cytogenetic analyses of
      further interstitial 10q deletions are necessary to assess whether the phenotypic
      manifestations differ between deletions that are interstitial compared to those
      that include also the terminal region of chromosome 10.

PMID- 16088868
TI  - A semi-quantitative microarray method to detect fetal RNAs in maternal plasma.
AB  - OBJECTIVES: To set up a semi-quantitative microarray method for the detection of
      fetal RNAs in maternal plasma. METHODS: We developed a semi-quantitative
      microarray method for the detection of placental RNA in maternal plasma. Firstly,
      the selected fetal RNAs were linearly amplified from the maternal plasma and then
      fluorescently labeled as the target DNAs. Finally, the targets were hybridized
      and detected by capturing DNA probes on a microarray slide. Two genes of beta
      subunit of human chorionic gonadotrophin (beta-hCG) and zinc finger gene on the Y
      chromosome (ZFY) were assayed with the microarray, and beta actin gene was used
      as an internal standard. Eighty-five pregnant women in the first trimester and
      the third trimester of gestation joined in this experiment, 14 of them also
      sampling in 36 h after delivery for the same assay. Real-time quantitative PCR
      was performed for comparison. RESULTS: It was found that the mRNA level of beta
      hCG decreased with the increasing of gestation age, and it was much higher in the
      carriers of the female fetus than in the carriers of the male fetus in the first
      trimester of gestation, which was consistent with the real-time quantitative PCR
      results. The results also reveal that delivery would result in the clearance of
      fetal mRNA in maternal plasma. CONCLUSIONS: The results suggest that the semi
      quantitative microarray method has great potential as a high-throughput assay in
      prenatal diagnosis and clinical laboratory.

PMID- 16088869
TI  - Structural elucidation of a new delta2-pyrazoline derivatives using 1H and 13C
      NMR spectroscopy.
AB  - This paper describes the unequivocal structural elucidation of a new kind of
      Delta2-pyrazoline derivatives carried out by means of monodimensional 1H and 13C
      NMR spectroscopies, bidimensional ones such as HMBC and HMQC experiments, and
      NOEDIFF effects. Conformational analysis of this molecule agrees very well with
      the experimentally NOEDIFF effects found.

PMID- 16088870
TI  - The nuclear actin-related protein Act3p/Arp4p is involved in the dynamics of
      chromatin-modulating complexes.
AB  - Chromatin remodelling and histone-modifying complexes govern the modulation of
      chromatin structure. While components of these complexes are diverse, nuclear
      actin-related proteins (Arps) have been repeatedly found in these complexes from
      yeast to mammals. In most cases, Arps are required for functioning of the
      complexes, but the molecular mechanisms of nuclear Arps have as yet been largely
      unknown. The Arps and actin, sharing a common ancestor, are supposed to be highly
      similar in the three-dimensional structure of their core regions, including the
      ATP-binding pocket. The Arp Act3p/Arp4p of Saccharomyces cerevisiae exists within
      the nucleus, partly as a component of several high molecular mass complexes,
      including the NuA4 histone acetyltransferase (HAT) complex, and partly as
      uncomplexed molecules. We observed that mutations in the putative ATP-binding
      pocket of Act3p/Arp4p increased its concentration in the high molecular mass
      complexes and, conversely, that an excess of ATP or ATPgammaS led to the release
      of wild-type Act3p/Arp4p from the complexes. These results suggest a requirement
      of ATP binding by Act3p/Arp4p for its dissociation from the complexes. In
      accordance, a mutation in the putative ATP binding site of Act3p/Arp4p inhibited
      the conversion of the NuA4 complex into the smaller piccoloNuA4, which does not
      contain Act3p/Arp4p and exhibits HAT activity distinct from that of NuA4.
      Although the in vitro binding activity of ATP by recombinant Act3p/Arp4p was
      found to be rather weak, our observations, taken together, suggest that the ATP
      binding pocket of Act3p/Arp4p is involved in the function of chromatin modulating
      complexes by regulating their dynamics.

PMID- 16088871
TI  - A high-efficiency method to replace essential genes with mutant alleles in yeast.
AB  - Temperature-sensitive (TS), internally deleted and truncated alleles are
      important tools to facilitate the characterization of essential genes. We have
      developed a straightforward method to replace a wild-type gene with a mutant
      allele at the endogenous locus. This method is an efficient alternative to the
      two-step method for integration of alleles that are compromised in function or
      contain multiple mutations. A strain is constructed that has the essential gene
      of interest disrupted by a selectable marker. Strain viability is maintained by a
      plasmid carrying a copy of the essential wild-type gene and the ADE3 gene. The
      mutant allele is cloned into an integratable vector carrying a selectable/counter
      selectable marker, such as URA3. The plasmid is linearized and transformed,
      directing integration to the 5' or 3' region flanking the essential open reading
      frame (ORF). Transformants that have integrated the mutant gene at the endogenous
      locus can lose the autonomous plasmid carrying the wild-type copy of the
      essential gene and the ADE3 gene. These transformants are identifiable as white
      sectoring colonies, display the mutant phenotype and may be characterized. An
      optional second selection step on 5-fluoroorotic acid (5-FOA) selects for popouts
      of the integrating vector sequences, leaves the mutant allele at the endogenous
      locus, and recycles selectable markers. We have used this method to integrate a
      TS allele of SPC110 that could not be integrated by standard methods.

PMID- 16088872
TI  - Maltotriose utilization in lager yeast strains: MTT1 encodes a maltotriose
      transporter.
AB  - Maltotriose is the second most abundant fermentable sugar in wort and, due to
      incomplete fermentation, residual maltotriose in beer causes both quality and
      economic problems in the brewing industry. To identify genes that might improve
      utilization of maltotriose, we developed a library containing genomic DNA from
      four lager strains and a laboratory Saccharomyces cerevisiae strain and isolated
      transformants that could grow on YP/2% maltotriose in the presence of 3 mg/l of
      the respiratory inhibitor antimycin A. In this way we found a gene which shared
      74% similarity with MPH2 and MPH3, 62% similarity with AGT1 and 91% similarity
      with MAL61 and MAL31, all encoding known maltose transporters. Moreover, the gene
      shared an even higher similarity (98%) with the uncharacterized Saccharomyces
      pastorianus mty1 gene (M. Salema-Oom, unpublished; NCBI Accession No. AJ491328).
      Therefore, we named the gene MTT1 (mty1-like transporter). We showed that the
      gene was present in four different lager strains but was absent from the
      laboratory strain CEN.PK113-7D. The ORF in the plasmid isolated from the library
      lacks 66 base pairs from the 3'-end of MTT1 but instead contains 54 bp of the
      vector. We named this ORF MTT1alt (NCBI Accession No. DQ010174). 14C-Maltose and
      repurified 14C-maltotriose were used to show that MTT1 and, especially, MTT1alt,
      encode maltose transporters for which the ratio between activities to maltotriose
      and maltose is higher than for most known maltose transporters. Introduction of
      MTT1 or MTT1alt into lager strain A15 raised maltotriose uptake by about 17% or
      105%, respectively.

PMID- 16088873
TI  - Cytosine deaminase MX cassettes as positive/negative selectable markers in
      Saccharomyces cerevisiae.
AB  - We describe positive/negative selectable cytosine deaminase MX cassettes for use
      in Saccharomyces cerevisiae. The basis of positive selection for cytosine
      deaminase (Fcy1) activity is that (a) fcy1 strains are unable to grow on medium
      containing cytosine as a sole nitrogen source and (b) fcy1 ura3 strains are
      unable to grow on medium containing cytosine as the sole pyrimidine source.
      Conversely, as 5-fluorocytosine (5FC) is toxic to cytosine deaminase-producing
      cells, fcy1 strains are resistant to 5FC. FCY1MX and FCA1MX cassettes, containing
      open reading frames (ORFs) of S. cerevisiae FCY1 and Candida albicans FCA1,
      respectively, were constructed and used to disrupt targeted genes in S.
      cerevisiae fcy1 strains. In addition, new direct repeat cassettes, kanPR, FCA1PR,
      FCY1PR and CaURA3PR, were developed to allow efficient deletion of target genes
      in cells containing MX3 repeats. Finally, the FCY1- and FCA1MX3 or PR direct
      repeat cassettes can be readily recycled after 5FC counter-selection on both
      synthetic and rich media.

PMID- 16088874
TI  - A rapid and simple procedure for high-efficiency lithium acetate transformation
      of cryopreserved Schizosaccharomyces pombe cells.
AB  - A rapid, simple, convenient, and highly efficient transformation of the fission
      yeast Schizosaccharomyces pombe has been developed. Freezing fission yeast cells
      in glycerol, a permeating cryoprotectant, with lithium acetate improved
      remarkably the transformation efficiency by one to two orders of magnitude. The
      optimum concentration of glycerol was found to be 30%, which is higher than that
      (10-15%) in the conventional cryopreservation of yeast cells. Glycerol not only
      played a role in cryopreserving the competent cells but also improved the
      transformation efficiency of the process. The thawed cell suspension with
      glycerol and lithium acetate was immediately mixed with carrier DNA, plasmid DNA
      and polyethylene glycol. Next, the mixture was heat shocked and directly spread
      on a selection plate. This simple procedure yielded more than 10(6)
      transformants/microg plasmid DNA, reducing the time required to only 20 min in
      total, including the thawing time. Furthermore, the frozen competent cells were
      stored long-term for more than 3 months without any significant loss of
      efficiency.

PMID- 16088875
TI  - Quantifying dynamic contrast-enhanced MRI of the knee in children with juvenile
      rheumatoid arthritis using an arterial input function (AIF) extracted from
      popliteal artery enhancement, and the effect of the choice of the AIF on the
      kinetic parameters.
AB  - Quantification of dynamic contrast-enhanced (DCE) MRI based on pharmacokinetic
      modeling requires specification of the arterial input function (AIF). A full
      representation of the plasma concentration data, including the initial rise and
      decay parts, considering the delay and dispersion of the bolus contrast is
      important. This work deals with modeling of DCE-MRI data from the knees of
      children with a history of juvenile rheumatoid arthritis (JRA) by using an AIF
      extracted from the signal enhancement data from the nearby popliteal artery.
      Three models for the AIFs were considered: a triexponential (AIF1), a gamma
      variate plus a biexponential (AIF2), and a biexponential (AIF3). The
      pharmacokinetic parameters obtained from the model were Ktrans', kep, and V'p.
      The results from AIF1 and AIF2 showed no statistically significant difference.
      However, some statistically significant differences were seen with AIF3,
      particularly for parameters Ktrans' and V'p in the synovium (SNVM). These results
      suggest the importance of obtaining an appropriate AIF representation in
      pharmacokinetic modeling of JRA. Specifically, the initial rising part of the AIF
      should be incorporated for optimal pharmacokinetic modeling results. The
      pharmacokinetic parameters (mean+/-SD) derived from AIF1, using the average
      plasma concentration data, were as follows: SNVM Ktrans'(min-1)=0.52+/-0.34,
      kep(min-1)=0.71+/-0.39, and V'p=0.33+/-0.16, and for the distal femoral physis
      (DFP) Ktrans'(min-1)=1.83+/-1.78, kep(min-1)=2.65+/-1.80, and V'p=0.46+/-0.31.
      The pharmacokinetic parameters in the SNVM may be useful for investigating
      activity and therapeutic efficacy in studies of JRA. Longitudinal studies are
      necessary to find or demonstrate the parameter that is more sensitive to disease
      activity.

PMID- 16088876
TI  - Microscopic magnetic resonance elastography (microMRE).
AB  - Magnetic resonance elastography (MRE) was extended to the microscopic scale to
      image low-frequency acoustic shear waves (typically less than 1 kHz) in soft gels
      and soft biological tissues with high spatial resolution (34 micromx34 micromx500
      microm). Microscopic MRE (microMRE) was applied to agarose gel phantoms, frog
      oocytes, and tissue-engineered adipogenic and osteogenic constructs. Analysis of
      the low-amplitude shear wave pattern in the samples allowed the material
      stiffness and viscous loss properties (complex shear stiffness) to be identified
      with high spatial resolution. microMRE experiments were conducted at 11.74 T in a
      56-mm vertical bore magnet with a 10 mm diameterx75 mm length cylindrical space
      available for the elastography imaging system. The acoustic signals were
      generated at 550-585 Hz using a piezoelectric transducer and high capacitive
      loading amplifier. Shear wave motion was applied in synchrony with the MR pulse
      sequence. The field of view (FOV) ranged from 4 to 14 mm for a typical slice
      thickness of 0.5 mm. Increasing the agarose gel concentration resulted in an
      increase in shear elasticity and shear viscosity. Shear wave motion propagated
      through the frog oocyte nucleus, enabling the measurement of its shear stiffness,
      and in vitro shear wave images displayed contrast between adipogenic and
      osteogenic tissue-engineered constructs. Further development of microMRE should
      enable its use in characterizing stiffer materials (e.g., polymers, composites,
      articular cartilage) and assessing with high resolution the mechanical properties
      of developing tissues.

PMID- 16088877
TI  - Cloning, sequencing and application of the LEU2 gene from the sour dough yeast
      Candida milleri.
AB  - We have cloned by complementation in Saccharomyces cerevisiae and sequenced a
      LEU2 gene from the sour dough yeast Candida milleri CBS 8195 and studied its
      chromosomal location. The LEU2 coding sequence was 1092 nt long encoding a
      putative beta-isopropylmalate dehydrogenase protein of 363 amino acids. The
      nucleotide sequence in the coding region had 71.6% identity to S. cerevisiae LEU2
      sequence. On the protein level, the identity of C. milleri Leu2p to S. cerevisiae
      Leu2p was 84.1%. The CmLEU2 DNA probe hybridized to one to three chromosomal
      bands and two or three BamHI restriction fragments in C. milleri but did not give
      any signal to chromosomes or restriction fragments of C. albicans, S. cerevisiae,
      S. exiguus or Torulaspora delbrueckii. Using CmLEU2 probe for DNA hybridization
      makes it easy to quickly identify C. milleri among other sour dough yeasts.

PMID- 16088879
TI  - Simulation of anisotropic growth of low-grade gliomas using diffusion tensor
      imaging.
AB  - A recent computational model of brain tumor growth, developed to better describe
      how gliomas invade through the adjacent brain parenchyma, is based on two major
      elements: cell proliferation and isotropic cell diffusion. On the basis of this
      model, glioma growth has been simulated in a virtual brain, provided by a 3D
      segmented MRI atlas. However, it is commonly accepted that glial cells
      preferentially migrate along the direction of fiber tracts. Therefore, in this
      paper, the model has been improved by including anisotropic extension of gliomas.
      The method is based on a cell diffusion tensor derived from water diffusion
      tensor (as given by MRI diffusion tensor imaging). Results of simulations have
      been compared with two clinical examples demonstrating typical growth patterns of
      low-grade gliomas centered around the insula. The shape and the kinetic evolution
      are better simulated with anisotropic rather than isotropic diffusion. The best
      fit is obtained when the anisotropy of the cell diffusion tensor is increased to
      greater anisotropy than the observed water diffusion tensor. The shape of the
      tumor is also influenced by the initial location of the tumor. Anisotropic brain
      tumor growth simulations provide a means to determine the initial location of a
      low-grade glioma as well as its cell diffusion tensor, both of which might
      reflect the biological characteristics of invasion.

PMID- 16088880
TI  - Improved data reconstruction method for GRAPPA.
AB  - This paper presents an improved data reconstruction method for generalized
      autocalibrating partially parallel acquisitions (GRAPPA) using multicolumn
      multiline interpolation (MCMLI). Both nearest acquired line (ky) neighboring
      points and column (kx) neighboring points from all components of an array coil
      were used to reconstruct each missing datum through interpolation. A new fitting
      scheme was designed to estimate the interpolation weights. Both simulations and
      in vivo experiments demonstrated that the proposed method yields higher-quality
      data reconstruction than the original GRAPPA method, especially with high
      acceleration factors.

PMID- 16088881
TI  - A PMR1-like calcium ATPase of Aspergillus fumigatus: cloning, identification and
      functional expression in S. cerevisiae.
AB  - The understanding of the controlling factors of calcium homeostasis in
      Aspergillus fumigatus is very poor, although this ion is involved in several
      important events of these particular cells. We have cloned, identified and
      expressed for functional complementation a PMR1-like Ca(2+)-ATPase gene from A.
      fumigatus. The Afpmr1 gene encodes a protein of 1061 deduced amino acids,
      containing all the conserved subdomains found in other P-type ATPases: the
      phosphatase region, phosphorylation site, FITC labelling site, ATP binding
      domain; E(386), N871, D875 amino acid residues for calcium ion interaction and
      Q880, a residue that alters ion selectivity in PMR1. The expressed AfPMR1 in S.
      cerevisiae K616 strain functionally complemented the deficient growth in EGTA (5
      20 mM)- and MnCl2 (4 mM)-containing medium. These results demonstrate the first
      evidence of a Ca(2+)-ATPase in A. fumigatus and strongly suggest a role for this
      enzyme in calcium and manganese homeostasis.

PMID- 16088883
TI  - Variable-density one-shot Fourier velocity encoding.
AB  - In areas of highly pulsatile and turbulent flow, real-time imaging with high
      temporal, spatial, and velocity resolution is essential. The use of 1D Fourier
      velocity encoding (FVE) was previously demonstrated for velocity measurement in
      real time, with fewer effects resulting from off-resonance. The application of
      variable-density sampling is proposed to improve velocity measurement without a
      significant increase in readout time or the addition of aliasing artifacts. Two
      sequence comparisons are presented to improve velocity resolution or increase the
      velocity field of view (FOV) to unambiguously measure velocities up to 5 m/s
      without aliasing. The results from a tube flow phantom, a stenosis phantom, and
      healthy volunteers are presented, along with a comparison of measurements using
      Doppler ultrasound (US). The studies confirm that variable-density acquisition of
      kz-kv space improves the velocity resolution and FOV of such data, with the
      greatest impact on the improvement of FOV to include velocities in stenotic
      ranges.

PMID- 16088884
TI  - Selective excitation of myelin water using inversion-recovery-based preparations.
AB  - T1 and T2 relaxation of excised frog sciatic nerve water was characterized at 7
      T. Based on these findings, optimal timings for multiple inversion-recovery
      magnetization preparations were determined to selectively excite the so-called
      myelin-water T2 component. Subsequent double inversion-recovery and triple
      inversion-recovery preparations were used in combination with CPMG acquisitions
      to experimentally determine optimal timings and effect of the preparation. Using
      double inversion-recovery, optimal timings were found to excite magnetization
      that is predominantly (approximately 93%) derived from the myelin-water
      component. Greater selectivity (approximately 96%) was found by extending the
      preparation to triple inversion-recovery, at the price of decreasing SNR by a
      factor of approximately 2.

PMID- 16088885
TI  - Practical approaches to the evaluation of signal-to-noise ratio performance with
      parallel imaging: application with cardiac imaging and a 32-channel cardiac coil.
AB  - In this work, two practical methods for the measurement of signal-to-noise-ratio
      (SNR) performance in parallel imaging are described. Phantoms and human studies
      were performed with a 32-channel cardiac coil in the context of ultrafast cardiac
      CINE imaging at 1.5 T using steady-state free precession (SSFP) and TSENSE. SNR
      and g-factor phantom measurements using a "multiple acquisition" method were
      compared to measurements from a "difference method". Excellent agreement was seen
      between the two methods, and the g-factor shows qualitative agreement with
      theoretical predictions from the literature. Examples of high temporal (42.6 ms)
      and spatial (2.1x2.1x8 mm3) resolution cardiac CINE SSFP images acquired from
      human volunteers using TSENSE are shown for acceleration factors up to 7. Image
      quality agrees qualitatively with phantom SNR measurements, suggesting an optimum
      acceleration of 4. With this acceleration, a cardiac function study consisting of
      6 image planes (3 short-axis views, 3 long-axis views) was obtained in an 18
      heartbeat breath-hold.

PMID- 16088886
TI  - Vital exhaustion and risk for cancer: a prospective cohort study on the
      association between depressive feelings, fatigue, and risk of cancer.
AB  - BACKGROUND: Vital exhaustion, defined as feelings of depression and fatigue, has
      previously been investigated mainly as a risk factor for cardiovascular disease.
      The authors investigated the association between depressive feelings and fatigue
      as covered by the concept of vital exhaustion and the risk for cancer. METHODS:
      The sample consisted of 8527 persons aged 21-94 who had been examined in 1991
      1994 within the Copenhagen City Heart Study. For the analysis, the sample was
      divided into quartiles on the basis of vital exhaustion scores. Cancer cases were
      ascertained by linkage to the Danish Cancer Registry. The mean length of follow
      up was 8.6 years. Regression analyses for etiology-based groups of cancer sites
      were conducted on the basis of the Cox proportional hazards model, with
      adjustment for a number of confounding variables. RESULTS: Cancer was diagnosed
      in 976 persons (12%) during follow-up. In comparison to those with the lowest
      scores, persons with the highest vital exhaustion scores had a significantly
      decreased risk for developing cancer at all sites (hazard ratio [HR], 0.80; 95%
      confidence interval [CI}, 0.66-0.96), smoking-related cancers (HR, 0.64; 95% CI,
      0.46-0.90), and virus and immune-related cancers (HR, 0.51; 95% CI, 0.26-0.99).
      No significant change in risk was found for cancers related to alcohol
      consumption or hormones. CONCLUSIONS: The results did not support the hypothesis
      that symptoms of fatigue and depression, as ascertained in the vital exhaustion
      index, increased the risk for cancer.

PMID- 16088887
TI  - The effect of changes in tumor size on breast carcinoma survival in the U.S.:
      1975-1999.
AB  - BACKGROUND: Temporal comparisons of case survival are commonly used to assess
      improvement in cancer treatment at the population level. However, such
      comparisons may be confounded by secular trends in disease prognosis, even within
      conventional stage categories. The objective of the current study was to
      characterize within-stage migration of tumor size in breast carcinoma, and to
      estimate the effect of this shift on reported breast carcinoma survival. METHODS:
      Population-based Surveillance, Epidemiology, and End Results (SEER) cancer
      registry data were used to evaluate secular trends in tumor size at the time of
      diagnosis and relative survival among localized and regional invasive breast
      carcinoma patients diagnosed between 1975-1999. Outcomes were stage-specific
      tumor size distribution, 5-year relative survival, relative survival standardized
      to the tumor size distribution of the cohort diagnosed between 1975-1979, and the
      percentage of improvement in relative survival attributable to shifts in tumor
      size distribution. RESULTS: Within each stage category, the proportion of smaller
      tumors increased significantly over time. Comparing patients diagnosed between
      1995-1999 with those diagnosed between 1975-1979, within-stage migration of tumor
      size accounted for 61% and 28%, respectively, of the relative survival increases
      noted in localized and regional breast carcinoma. CONCLUSIONS: The tumor size
      distribution of incident breast carcinomas in SEER has shifted toward smaller
      tumors. A substantial fraction of the improvement in breast carcinoma survival
      noted since 1975 may be attributable to within-stage migration of tumor size.

PMID- 16088888
TI  - Serum deprivation improves seeding and repopulation of acellular matrices with
      valvular interstitial cells.
AB  - Cell-extracted valvular tissues (acellular scaffolds, or aScaffolds) offer unique
      advantages over synthetic polymers for cardiac valve engineering applications in
      that they retain extracellular matrix molecules to support cellular ingrowth. The
      extracellular matrix is important in directing many cellular pathways, such as
      adhesion, proliferation, migration, differentiation, and survival. However,
      repopulating this type of scaffold often requires high seeding densities or
      recurrent cell delivery. The optimization of valvular interstitial cell (VIC)
      seeding onto aScaffolds is reported herein. VICs (the most prevalent cell type in
      valve leaflets) have maximal growth in 15-20% serum concentrations on tissue
      culture polystyrene. Interestingly, after VIC seeding onto aScaffolds, a
      reduction of serum content, from 15% serum to 5% or less, was found to increase
      significantly the number of adherent cells, as well as induce transfer of VICs
      from a tissue-culture polystyrene surface to the aScaffold. aScaffolds seeded and
      cultured with periods of reduced serum levels were shown to support and enhance
      VIC viability and attachment, as well as accelerate VIC migration into the
      aScaffold, leading to a uniformly repopulated valve leaflet construct after 4
      weeks of static culture.

PMID- 16088889
TI  - Comparison of implantation and cytotoxicity testing for initially toxic
      biomaterials.
AB  - To evaluate the predictive value of cytotoxicity testing, the present study
      compares the in vivo tissue responses to in vitro cytotoxicity before and after
      implantation. Material toxicity was caused by addition of the toxic substance
      Zincdiethyldithiocarbamate (ZDEC) that is used as a standard for in vitro
      cytotoxicity testing. Polyurethane discs with the addition of 0.5% or 1% ZDEC as
      well as nontoxic discs were inserted in the abdominal wall of rats for 1 day up
      to 6 weeks. After explantation the foreign body response was analyzed
      immunohistochemically. An in vitro reanalysis of the explanted reference
      materials (RMs) revealed remaining high concentrations of toxic compounds after 1
      week implantation, whereas no toxicity was seen after 6 weeks implantation. This
      was reflected in the foreign body response where a significantly thicker capsule
      and more inflammatory cells were seen at 1 week for the toxic implants. Over
      time, with decreasing toxicity, these differences disappeared. Test samples that
      only were subjected to in vitro extraction with water did not elute toxic
      compounds to the same extent as the in vivo conditions. It is concluded that many
      clinically useful implant materials may be unnecessarily rejected due to the
      results of in vitro tests.

PMID- 16088890
TI  - Prefabrication of vascularized bone graft using a combination of fibroblast
      growth factor-2 and vascular bundle implantation into a novel interconnected
      porous calcium hydroxyapatite ceramic.
AB  - The aim of this study was to create a prefabricated vascularized bone graft using
      a novel interconnected porous calcium hydroxyapatite ceramic (IP-CHA) by
      combining vascular bundle implantation and basic fibroblast growth factor (FGF)-2
      administration in a rabbit model. Twenty-four Japanese white rabbits were used.
      The saphenous artery and vein were passed through the hole of the IP-CHA. In an
      experimental group, 100 microg of FGF-2 was administered into the IP-CHA before
      implanting the vascular bundle. In the control group, the saline was administered
      into the IP-CHA before implanting the vascular bundle. Finally, the IP-CHA was
      placed subcutaneously in the medial thigh. Neovascularization from the vascular
      bundle was evaluated at 2 weeks after surgery, and osteogenesis was evaluated at
      4 weeks. At 2 weeks, the length and density of newly formed vessels were
      significantly greater in the experimental group than in the control group.
      Histological evaluation showed osteoid deposition in the pores of the IP-CHA at 4
      weeks in the experimental group, whereas no evidence of osteoid deposition was
      noted in the control group. This study showed the potential of creating a
      vascularized bone graft of a predetermined size and shape using a combination of
      FGF-2 and vascular bundle implantation in the IP-CHA.

PMID- 16088891
TI  - Suppression of polyethylene particle-induced osteolysis by exogenous
      osteoprotegerin.
AB  - Alterations of the key regulators of osteoclastogenesis, receptor activator of NF
      kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) have been
      implicated in wear particle-induced osteolysis, the most common cause for implant
      failure in total joint replacements. This study investigated the effect of
      exogenous OPG on ultra-high-molecular-weight polyethylene (UHMWPE) particle
      induced osteolysis. The murine calvarial osteolysis model was utilized in 28
      C57BL/6J mice randomized to four groups. Group I underwent sham surgery only,
      group II received UHMWPE particles, and group III and IV particles and
      subcutaneous OPG starting from day 0 (group III) or day 5 (group IV) until
      sacrifice. After 2 weeks, calvaria were prepared for histology and
      histomorphometry. Bone resorption was measured within the midline suture using
      Giemsa staining and osteoclast numbers were determined using TRAP staining.
      UHMWPE particle implantation resulted in grossly pronounced osteoclastogenesis
      and bone resorption. Both immediate and delayed treatment with OPG counteracted
      these particle-induced effects significantly, suppressing osteoclast formation
      and bone resorption (p < 0.001 and p < 0.001, respectively). In conclusion,
      exogenous OPG markedly suppressed UHMWPE particle-induced osteolysis in a murine
      calvarial model. This important finding underscores the crucial significance of
      the OPG-RANKL-RANK signaling in wear particle-induced osteolysis. Exogenous OPG
      may prove an effective treatment modality for wear debris-mediated periprosthetic
      osteolysis after total joint arthroplasty.

PMID- 16088892
TI  - Novel PEX1 coding mutations and 5' UTR regulatory polymorphisms.
AB  - Zellweger syndrome and its milder variants--neonatal adrenoleukodystrophy and
      infantile Refsum disease--comprise a clinical continuum of diseases referred to
      as the Zellweger spectrum. Mutations in the PEX1 gene, which consists of 24 exons
      and encodes a AAA ATPase protein required for peroxisomal protein import, account
      for approximately two-thirds of the known Zellweger spectrum patient mutations.
      In this paper, we report on four novel PEX1 mutations and two polymorphisms in an
      Australasian cohort. Two of the mutations--c.1108_1109insA and c.2391_2392delTC-
      that lead to the introduction of a premature termination codon in exons 5 and 14,
      respectively, are associated with the severe Zellweger phenotype. One patient
      with a milder disease phenotype was a compound heterozygote for two missense
      mutations (I989T and R998Q), both affecting amino acids in the second, C-terminal
      AAA domain of the protein. PTS1 protein import levels in cultured skin
      fibroblasts from this patient were almost 20% of normal control levels. We have
      also characterized two co-segregating polymorphisms in the 5' UTR of the PEX1
      gene. Based on reporter assays, the c.-137T>C polymorphism leads to reduced PEX1
      expression, whereas the c.-53C>G polymorphism leads to increased expression. When
      present together, these regulatory polymorphisms lead to near-normal PEX1
      expression. Altered PEX1 expression due to the presence of either the c.-137T>C
      or the c.-53C>G variant could impact on residual PEX1 function if another co
      allelic mutation was present which did not completely abolish PEX1 function. It
      also follows that the presence of polymorphisms in the PEX1 promoter region could
      have implications for patients with mutations in other PEX proteins known to
      interact with PEX1, such as PEX6. Thus, although not deleterious in control
      individuals, these polymorphisms could contribute to phenotypic heterogeneity
      among Zellweger spectrum patients.

PMID- 16088893
TI  - In vitro induction of polyploidy and chromatid exchanges by culture medium
      extracts of natural rubbers compounded with 2-mercaptobenzothiazole as a positive
      control candidate for genotoxicity tests.
AB  - We tested extracts of custom-made natural rubber samples for cytotoxicity using
      V79 cells and for chromosome aberration (CA) induction using CHL cells in
      compliance with the Japanese guidelines for basic biological tests of medical
      materials and devices. The samples were formulated with a high level of 2
      mercaptobenzothiazole (MBT) (A); a low level of MBT (B); or zinc
      dibutyldithiocarbamate (ZDBC) (C). In the CA test, MBT induced mainly polyploidy,
      including endoreduplication, and ZDBC induced structural CAs. In the cytotoxicity
      test, culture medium extracts of A, B, and C suppressed colony formation to 50%
      of the control value at 53.1%, 94.3%, and >100%, respectively. Culture medium
      extracts of sample A induced polyploidy and structural CAs in the absence of an
      exogenous metabolic activation system (S9 mix), but at lower concentrations in
      its presence, indicating the existence of other leachable promutagens. The
      extracts of sample B induced structural CAs at the highest concentration and only
      with S9 mix. Sample C was negative. The facts suggest that sample A may be a
      candidate for a positive control for genotoxicity tests. The high frequency of
      polyploidy induced by sample A was not predicted by MBT, suggesting the
      usefulness of the test for safety evaluation of medical devices. Numerical CAs
      induced by MBT and sample A are discussed.

PMID- 16088894
TI  - A preliminary in vitro and in vivo study of the effects of new anthraquinones on
      neutrophils and bone remodeling.
AB  - Osteolysis, that is, progressive periprosthetic bone loss, is responsible for
      approximately 70% of aseptic loosening and implant failure. Usually, it is due to
      a granulomatous reaction wear-induced, leading to macrophage and osteoclast
      mediated bone resorption. At present, there is no established prophylaxis or
      treatment for this process. For this purpose, as a preliminary investigation, we
      aimed to study the effects in two directions, inhibition of proinflammatory
      signals, and bone remodeling activity, of two newly synthesized anthraquinone
      molecules [N,N'-Diethylamino-2,6-anthraquinone-disulfonamide (GR375) and N,N'-(p
      ethoxyphenyl)-2,6-anthraquinone-disulfon amide (GR377)]. Among the pro
      inflammatory signals, the ability of the two anthraquinones to interfere with the
      production of superoxide anion (O(2) (-)), which was assumed as a marker of
      reactive oxygen species (ROS), was evaluated in an in vitro cell model by testing
      phagocytes, such as human neutrophils, challenged by the chemotactic agent N
      formylmethionyl-leucyl-phenylalanine (FMLP). Both compounds inhibited O(2) (-)
      production, in a dose-dependent way, without exerting scavenger effects. An in
      vivo model was applied to investigate their effect on bone remodeling. Fifty-four
      female Wistar rats were divided into eight groups of six animals each, and a 4
      week treatment was applied in two phases. A 25 mg/kg/os dose in the first phase
      and 12.5-6.25 mg/kg/os doses in the second one were employed. The tibia
      trabecular bone at the secondary spongiosa level was analyzed, and trabecular
      bone volume (%TBV), trabecular thickness (TbTh), and apatite lattice parameters
      were measured. At the highest doses of GR375 and GR377 the %TBV and the TbTh
      increased by 33.2, 34.6%, and 3.6 and 9.1%, respectively, whereas
      crystallographic parameters were not significantly different from the untreated
      group. Our results suggest a simultaneous antiinflammatory and antiosteoclastic
      activity of both drugs that encourages to perform further research. If it will be
      confirmed, they could be proposed in a variety of bone diseases, in particular,
      when acute inflammation is associated to osteolytic processes and, eventually, in
      the prevention and treatment of periprosthetic osteolysis.

PMID- 16088895
TI  - Prolonged duration local anesthesia with lipid-protein-sugar particles containing
      bupivacaine and dexamethasone.
AB  - Glucocorticoids prolong block duration from polymeric microspheres containing
      bupivacaine, but not from unencapsulated drug. Here we investigate this effect
      applies to particles with much more rapid drug release and improved long-term
      biocompatibility. Male Sprague-Dawley rats were given sciatic nerve blocks with
      75 mg of 3% or 60% (w/w) dipalmitoylphosphatidylcholine (DPPC) spray-dried lipid
      protein-sugar particles (LPSPs) containing 10% (w/w) bupivacaine and 0%, 0.05%,
      or 0.1% (w/w) dexamethasone. Sensory nerve block from bupivacaine-containing 3%
      and 60% (w/w) DPPC particles without dexamethasone yielded blocks lasting 301 +/-
      56 and 321 +/- 127 min, respectively. Addition of 0.05% (w/w) dexamethasone
      increased block durations to 610 +/- 182 and 538 +/- 222 min, respectively;
      increasing dexamethasone loading to 0.1% did not further increase duration. One
      day after injection, dexamethasone-containing particles resulted in lower
      inflammation scores and capsule thickness than dexamethasone-free particles, but
      the difference was gone by day 4. Excipient composition had prominent effects at
      all time points. For all groups, inflammation was largely resolved by 2 weeks
      after injection. Dexamethasone approximately doubled the duration of nerve block
      from bupivacaine-loaded LPSPs, while maintaining excellent biocompatibility. Such
      formulations could be useful in clinical applications when nerve blockade is
      needed for 24 hours or less.

PMID- 16088896
TI  - A multiplex PCR method for the detection of all five individual genes of ica
      locus in Staphylococcus epidermidis. A survey on 400 clinical isolates from
      prosthesis-associated infections.
AB  - In Staphylococcus epidermidis, ica locus encodes for the synthesis of a
      polysaccharide intercellular adhesin (slime or biofilm). A multiplex polymerase
      chain reaction (PCR) for the detection of the five individual genes of ica locus
      was developed, with the aim to probe the set of genes in a large collection of
      Staphylococcus epidermidis clinical isolates. Single representative fragments for
      icaR, icaA, icaD, icaB, and icaC genes were selected. Multiplex PCR was applied
      to two reference Staphylococcus epidermidis strains [the non-biofilm-forming ATCC
      12228 and the biofilm-forming ATCC 35984 (RP62A)] and to 400 clinical isolates of
      Staphylococcus epidermidis from orthopedic prosthesis associated infections. The
      gene profile was compared with the phenotypic biofilm-forming ability, evaluated
      by means of an optimized Congo red agar (CRA) plate test. Among the clinical
      isolates, 228 (57%) turned out completely ica positive and were biofilm
      producing. Among the 172 non-biofilm-forming strains (43%), 164 (41%) were
      completely ica negative and 8 strains (2%) harbored all five ica genes. The ica
      locus thus proves to be a cluster of strictly linked genes, without any evidence
      of single gene deletion.

PMID- 16088897
TI  - Pesticides, microbial functions and biodiversity in soil. Proceedings of the 4th
      International Symposium on Environmental Aspects of Pesticide Microbiology.
      September 4-9, 2004. Thessaloniki, Greece.

PMID- 16088898
TI  - Defect-induced fatigue microcrack formation in cement mantle.
AB  - Acoustic emission (AE) was used to monitor the progress of the fatigue damage
      process in the cement mantles of two cemented femur stem constructs that
      contained naturally occurring defects. After the fatigue tests, morphological
      features of the defects were investigated using an environmental scanning
      electron microscope. It showed that the regions with no visible defects were
      mainly microcrack free, whereas the defect regions were the main sources
      generating microcracks. Two types of microcracks were identified: type I and type
      II. Signal energies associated with type I microcracks were about an order of
      magnitude higher than that of type II. The microstructural investigations of the
      defects and the areas in the vicinity of the defects suggested their
      categorization into stable and unstable. The accumulative energy-time
      relationships revealed that stable and unstable microcrack curves had convex
      [formula: see text], and concave [formula: see text] shapes, respectively. The
      progress of fatigue microcrack formation occurred over three distinct phases:
      initiation, transition, and stableness.

PMID- 16088899
TI  - Evaluation of calcium titanate as apatite growth promoter.
AB  - Calcium titanate (CaTiO(3), perovskite) has been used to determine its apatite
      nucleation ability and propose a possible nucleation initial step. Measurements
      of calcium leaching from the calcium titanate surface and phosphate adsorption
      experiments were carried out separately by using commercial calcium titanate
      suspensions at room temperature. Adsorption behaviour determined by zeta
      potential measurements shows that phosphate is strongly adsorbed on the calcium
      titanate surface. It was found that the higher the pH, the higher the Ca present
      on the calcium titanate surface, but phosphate adsorption followed this trend
      only up to pH 7.4. Results suggest that phosphate ions are not adsorbed only on
      Ca sites but also on TiO(2) groups sites of the surface, formed after calcium
      leaching from the surface. When both ions are simultaneously added in a modified
      simulated body fluid containing calcium titanate, at 37 degrees C, apatite growth
      occurs on its surface after 1 week of immersion.

PMID- 16088900
TI  - Development of multifunctional polymer-mineral composite materials for bone
      tissue engineering.
AB  - The main goal of this article is the development of a novel approach to construct
      multifunctional composite scaffolds for bone tissue engineering. For this
      purpose, different kinds of mineral macroporous supports, water-soluble aldehyde
      containing copolymers of N-vinylpyrrolidone, as well as different nonspecific and
      biospecific ligands governing cell adhesion and growth have been used. The
      composite materials were tested initially for cytotoxicity in cell culture
      experiments using a model cell line.

PMID- 16088901
TI  - The effects of calcium phosphate deposition upon corrosion of CoCr alloys and the
      potential for implant failure.
AB  - Physical wear of orthopedic implants is inevitable. CoCr metal samples, typically
      used in joint reconstruction, corrode rapidly after removal of the protective
      oxide layer. The behavior of CoCr pellets immersed in human serum, fetal bovine
      serum (FBS), synovial fluid, and water were studied using time-of-flight
      secondary ion mass spectroscopy (ToF-SIMS). The differences in the corrosive
      nature of human serum, FBS, synovial fluid, and water after 5 days immersion were
      highlighted by the oxide/hydroxide layer, which was, respectively, 25, 10, 1.5,
      and 3-3.5 nm thick. The thickness of calcium phosphate deposit from human serum,
      FBS, and synovial fluid was, respectively, 30, 20, and 2 nm. Co and Cr ions
      migrated from the bulk metal surface and were trapped in the serum deposits,
      where chromium existed as oxides, hydroxides, and phosphates, whereas the cobalt
      chemistry was dominated only by phosphates and hydroxides. This may account for
      the composition of wear debris from CoCr orthopedic implants, which are
      predominantly hydroxyphosphate compounds. From the literature, proteoglycans,
      pyrophosphates, phospholipids, lubricin, and superficial zone protein (SZP) have
      been identified as possible causes for the insignificant deposit of calcium
      phosphate from synovial fluid. Circulation of these compounds around the whole
      implant may inhibit calcium phosphate deposition and therefore contribute to
      osteolysis.

PMID- 16088902
TI  - Permeable guidance channels containing microfilament scaffolds enhance axon
      growth and maturation.
AB  - Successful peripheral nerve regeneration is still limited in artificial conduits,
      especially for long lesion gaps. In this study, porous poly(L-lactide-co-DL
      lactide, 75:25) (PLA) conduits were manufactured with 16 poly(L-lactide) (PLLA)
      microfilaments aligned inside the lumen. Fourteen and 18 mm lesion gaps were
      created in a rat sciatic nerve lesion model. To evaluate the combined effect of
      permeable PLA conduits and microfilament bundles on axon growth, four types of
      implants were tested for each lesion gap: PLA conduits with 16 filaments; PLA
      conduits without filaments; silicone conduits with 16 filaments; and silicone
      conduits without filaments. Ten weeks following implantation, regeneration within
      the distal nerve was compared between corresponding groups. Antibodies against
      the markers S100, calcitonin gene related peptide (CGRP), RMDO95, and P0 were
      used to identify Schwann cells, unmyelinated axons, myelinated axons, and myelin,
      respectively. Results demonstrated that the filament scaffold enhanced tissue
      cable formation and Schwann cell migration in all groups. The filament scaffold
      enhanced axonal regeneration toward the distal stump, especially across long
      lesion gaps, but significance was only achieved with PLA conduits. When compared
      to corresponding silicone conduits, permeable PLA conduits enhanced myelinated
      axon regeneration across both lesion gaps and achieved significance only in
      combination with filament scaffolds. Myelin staining indicated PLA conduits
      supported axon myelination with better myelin quantity and quality when compared
      to silicone conduits.

PMID- 16088903
TI  - Pesticides, microbial functions and biodiversity in soil.

PMID- 16088904
TI  - Bioactive and biocompatible pieces of HA/sol-gel glass mixtures obtained by the
      gel-casting method.
AB  - Hydroxyapatite (HA)/glass mixtures have shown a faster bioactive behaviour than
      HA itself. On the other hand, the gel-casting method is a simple and reproducible
      colloidal method to produce ceramic pieces with complex shapes. In this work,
      pieces of HA/glass mixtures were prepared by the gel-casting method. A study for
      obtaining concentrated slurries of these mixtures is reported; the bioactivity
      and biocompatibility of the obtained pieces have been studied also. The influence
      of pH, dispersant concentration, the content and milling of glass, and the way to
      prepare the suspensions were investigated. The lowest viscosity and better
      rheological properties were achieved with the lowest glass content, when the
      glass was added after the dispersion of the HA powder and when the glass was not
      milled after calcination. Fluid suspensions with a high solid content (50 vol.%)
      could be prepared and well-shaped pieces were obtained from these slurries. These
      pieces showed in vitro bioactive behavior in simulated body fluid; additionally,
      the proliferation and spreading assays with osteoblastic cells (HOS) showed that
      the pieces are biocompatible. The results obtained indicate that the gel-casting
      of HA/glass mixtures produces bioactive and biocompatible pieces with the
      required shapes. Therefore, these materials could be good candidates for clinical
      applications and scaffolds for tissue engineering.

PMID- 16088905
TI  - Fatigue of kidney stones with heterogeneous microstructure subjected to shock
      wave lithotripsy.
AB  - In this article a theoretical framework is developed for the mechanics of kidney
      stones with an isotropic, random microstructure--such as those comprised of
      cystine or struvite. The approach is based on a micromechanical description of
      kidney stones comprised of crystals in a binding matrix. Stress concentration
      functions are developed to determine load sharing of the particle phase and the
      binding matrix phase. Measurements have shown the inclusions to be considerably
      harder than the binder; consequently, loading of a stone leads to higher stresses
      in the inclusions than in the binder. As an illustration of the theory, the
      fatigue of kidney stones subject to shock-wave lithotripsy is considered. Stress
      concentration functions are used to construct fatigue-life estimates for each
      phase, as a function of the volume fraction and of the mechanical properties of
      the constituents, as well as the loading from SWL. The failure of the binding
      matrix, or of the particulate phase, is determined explicitly in a model for the
      accumulation of distributed damage. The theory can be used to assess the
      importance of microscale heterogeneity on the comminution of renal calculi, and
      to estimate the number of cycles to failure in terms of measurable material
      properties.

PMID- 16088906
TI  - Homozygous microdeletion of chromosome 4q11-q12 causes severe limb-girdle
      muscular dystrophy type 2E with joint hyperlaxity and contractures.
AB  - Microdeletion syndromes are commonly transmitted as dominant traits and are
      frequently associated with variably expressed pleiotropic phenotypes. Nonlethal
      homozygous microdeletions, on the other hand, are very rare. Here, we delineate
      the fifth and so far largest homozygous microdeletion in nonmalignancies of
      approximately 400 kb on chromosome 4q11-q12 in a large consanguineous East
      Anatolian family with six affected patients. The deleted region contains the beta
      sarcoglycan gene (SGCB), the predicted gene SPATA18 (spermatogenesis associated
      18 homolog) and several expressed sequence tags. Patients presented with a severe
      and progressive Duchenne-like muscular dystrophy phenotype, a combination of
      hyperlaxity and joint contractures, chest pain, palpitations, and dyspnea.

PMID- 16088907
TI  - Twenty-four novel mutations in Wilson disease patients of predominantly European
      ancestry.
AB  - Wilson disease (WND), an autosomal recessive disorder of copper transport, shows
      wide genotypic and phenotypic variability, with hepatic and/or neurological
      symptoms. The WND gene, ATP7B, encodes a copper transporting ATPase that is
      involved in the transport of copper into the plasma protein ceruloplasmin, and in
      the excretion of copper from the liver. ATP7B mutations result in copper storage
      in liver and brain. From 247 WND patients worldwide whose DNA has been sequenced
      in our laboratory, we have identified 24 new mutations. The origins of the
      patients were European white (one deletion, one nonsense, one splice site, and 18
      missense), Chinese (one deletion, one missense) and Bangladeshi (one missense).
      Most of these had strong support as disease causing mutations, based on
      conservation between species, structural changes, and absence in controls. One
      missense mutation in a Chinese patient was considered uncertain because of its
      conservative nature and position in the protein. We also identified 15 nucleotide
      substitutions (11 of them new) causing silent or intronic changes, none of which
      produce an additional splice site that could lead to disease. Characterization of
      mutations, both disease-causing and normal variants, is essential for accurate
      molecular diagnosis of this condition.

PMID- 16088908
TI  - Novel EXT1 and EXT2 mutations identified by DHPLC in Italian patients with
      multiple osteochondromas.
AB  - We describe the results of an optimised DHPLC-based mutation screening of the
      EXT1 and EXT2 genes in Italian patients affected by multiple osteochondromas [MO;
      also referred to as hereditary multiple exostoses (HME) in the literature], using
      a multistep approach. We first analysed 36 unrelated probands for EXT1 mutations
      by DHPLC analysis and subsequent direct sequencing of all samples with abnormal
      elution profile. Negative cases were then screened for EXT2 mutations using the
      same approach. In patients who tested normal at DHPLC screening, all EXT1 and
      EXT2 exons and splice-site junctions were directly sequenced. In 7 informative
      families, we also performed a pre-screening linkage analysis to selectively focus
      the DHPLC testing on the EXT1 or EXT2 gene. We detected 31 MO-related mutations,
      of which 23 (74%) were novel. Seven polymorphisms were also found. Twenty-four
      mutations (77%) were found in EXT1 and 7 (23%) in EXT2. No disease-causing
      mutations were detected in five of 36 patients, with a mutation frequency of 86%.
      According with previous studies, most mutations (90%) are loss of function.
      Neither false positive nor false negative results were obtained. This multistep
      method can be considered a fast and reliable diagnostic strategy for the
      detection of EXT1/2 mutations, with excellent sensitivity and specificity.

PMID- 16088909
TI  - Schmid type of metaphyseal chondrodysplasia and COL10A1 mutations--findings in 10
      patients.
AB  - The Schmid type of metaphyseal chondrodyplasia (MCDS) is characterized by short
      stature, widened growth plates, and bowing of the long bones. It results from
      autosomal dominant mutations of COL10A1, the gene which encodes alpha1(X) chains
      of type X collagen. We report the clinical and radiographic findings in 10
      patients with MCDS and COL10A1 mutations. Six patients had lower limb
      deformities, which necessitated orthopedic surgeries in all of them. One patient
      demonstrated no deformities and normal stature at age 11 years (height -1.2 SDS)
      while the others manifested severe short stature (<-3.5 SDS). Radiographs showed
      metaphyseal changes which were most pronounced at the hips and knees. Five of the
      identified 10 mutations in COL10A1 were novel. Six mutations resulted in
      truncation of the NC1 domain while four mutations were single amino-acid
      substitutions. Our findings suggest that COL10A1 mutations result in a uniform
      pattern of growth plate abnormalities. However, the clinical variability in
      severity among affected individuals is greater than previously thought.

PMID- 16088910
TI  - A patient with mutations in DNA Ligase IV: clinical features and overlap with
      Nijmegen breakage syndrome.
AB  - The clinical phenotype of Ligase IV syndrome (LIG4 syndrome), an extremely rare
      autosomal recessive condition caused by mutations in the LIG4 gene, closely
      resembles that of Nijmegen breakage syndrome (NBS), and is characterized by
      microcephaly, characteristic facial features, growth retardation, developmental
      delay, and immunodeficiency. We report a 4(1/2)-year-old boy who presented with
      acute T-cell leukemia. The facial gestalt was strongly reminiscent of NBS. The
      patient died shortly after the onset of treatment for his T-cell leukemia.
      Subsequent chromosome breakage studies showed a high rate of breakage in a
      fibroblast culture. Radiosensitivity was assessed by a colony survival assay; the
      results showed radiosensitivity greater than is typically seen in NBS. Mutation
      screening of the NBS1 gene was negative. Sequencing of the LIG4 gene revealed a
      homozygous truncating mutation 2440 C>T (R814X). Although this mutation has been
      previously noted in LIG4 syndrome, this patient is the first reported homozygote
      for the mutation. In this study, we review the clinical features of this rare
      syndrome and provide suggestions for differential diagnosis.

PMID- 16088911
TI  - Mutation spectrum of the APC gene in 83 Korean FAP families.
AB  - Familial adenomatous polyposis (FAP) is a clinically well-defined hereditary
      disease caused by germline mutations in the adenomatous polyposis coli (APC)
      gene. FAP is characterized by polyposis in the large bowel and variable
      extracolonic manifestations. With an increase of reported APC germline mutations,
      many reports have investigated genotype-phenotype correlations in FAP patients.
      Here, we analyzed the APC gene for germline mutations in 83 unrelated Korean FAP
      patients and investigated genotype-phenotype correlations. We identified germline
      APC mutations in 59 (71%) of the cases, including 34 frameshift mutations, 19
      nonsense mutations, and six splice site mutations. Among 59 patients with the
      identified germline mutation of the APC gene, 37 had been reported previously and
      were included in the genotype-phenotype analysis. In the other 22 patients, we
      identified seven novel mutations: c.1438C>T, c.2232_2233dupCT, c.3426delT,
      c.3739_3769del31, c.3931_3935delATTGG, c.4332dupA, and c.4722_4725delACTA.
      Desmoid tumors were identified in six of the examined FAP patients, five of whom
      had APC germline mutations; these mutations involved codons 849, 864, 1309, 1444
      and 1464, respectively (c.2547_2548delTA, c.2592_2593insCT, c.3927_3931delAAAGA,
      c.4332dupA and c.4391-4394delAGAG). Four of the included FAP patients had
      papillary thyroid cancers; all were female and had germline APC mutations
      (c.1863_1865delTTAincCT, c.2805C>A, c.3183_3187delACAAA and c.3927_3931delAAAGA).

PMID- 16088912
TI  - Growth deficiency, facial anomalies, and brachydactyly (Frias syndrome): a second
      family.
AB  - A second family with the condition first described by Frias et al. in 1975 is
      presented. Those authors examined a mother and her son affected with short
      stature, facial anomalies (epicanthic folds, downward palpebral fissures,
      hyperthelorism, and eyelid ptosis), cup-shaped and posteriorly rotated ears, hand
      and foot defects, and delayed bone age. In the family we are presenting here, a
      girl, her mother, the mother's brother, and the propositus' maternal grandmother,
      were affected. This supports autosomal dominant inheritance, as proposed by
      (Frias et al. [1975] BDOAS 11:30-33), although with variable expressivity.

PMID- 16088914
TI  - Familial visceral neuropathy: a defined entity?
AB  - Familial visceral neuropathy (FVN) is a heterogeneous group of disorders due to
      abnormalities of the myenteric plexus. FVN with neuronal intranuclear inclusions
      is one particular form of FVN with a variable phenotype that includes achalasia,
      gastro-esophageal reflux, intestinal dysmotility and pseudo-obstruction,
      dysarthria, peripheral neuropathy and pupillary defects, and the presence of
      intranuclear inclusions within the neurons of the enteric nervous system. We
      present a four-generation family in which 10 individuals (7 of whom have been
      examined) are affected with FVN. The family was previously reported as familial
      esophageal achalasia, an autosomal recessive condition (MIM200400). At that time,
      several individuals in a single sibship were affected and there were no
      manifestations in either parent. Since that report, two individuals have had
      affected children and the mother has developed symptoms and has abnormalities on
      electromyography, thus enabling us to reclassify the family. This family provides
      further evidence of autosomal dominant inheritance, with marked variation in
      expression.

PMID- 16088913
TI  - Clefting, amniotic bands, and polydactyly: a distinct phenotype that supports an
      intrinsic mechanism for amniotic band sequence.
AB  - Amniotic band sequence (ABS) is a well-described condition involving a variety of
      congenital anomalies in association with fibrous bands. However, many cases are
      associated with birth defects that are not readily explained by the mechanism of
      fibrous strings entangling body parts and causing disruption of the fetal
      structures. The most common of these is typical cleft lip and palate (CLP). Here
      we describe such a case, with typical ABS limb defects and constriction bands,
      along with CLP, supernumerary left nipple, polydactyly, and a skin papilla. This
      case is nearly identical to a child previously described by Guion-Almieda and
      Richieri-Costa [2000] and may, therefore, represent a previously unrecognized
      syndrome that overlaps with ABS. Furthermore it may be that cases with ABS-like
      anomalies associated with CLP represent a different condition, possibly caused by
      mutations in the genes Disorganization, p63, or IRF6.

PMID- 16088915
TI  - Novel amino acid substitution in the Y-position of collagen type II causes
      spondyloepimetaphyseal dysplasia congenita.
AB  - We report on monozygotic twins with short stature and severe
      spondyloepimetaphyseal dysplasia congenita (SEMDC) from the Polish population.
      Phenotype of the twin girls resembles spondyloepiphyseal dysplasia congenita
      Spranger-Wiedemann (SEDC-SW), but shortening of the stature is more severe and
      the cranioface is normal. The distinctive radiographic features, in spite of
      similarity to SEDC-SW, indicate different spinal and, notably, severe metaphyseal
      involvement. Molecular analysis of the COL2A1 gene revealed an A to G transition
      at nucleotide +79 of exon 41 that converted the codon for arginine at amino acid
      792 to a codon for glycine (Arg792Gly). The twins were heterozygous for the
      mutation and neither parent had this change. The Arg792Gly substitution is
      located at the Y-position of Gly-X-Y triplet, and it is likely that this
      substitution decreased the thermal stability of the triple helix and may affect
      fibril growth by replacement of an arginine residue, which is important for a
      conformation of the triple helix.

PMID- 16088916
TI  - High prevalence of the W24X mutation in the gene encoding connexin-26 (GJB2) in
      Spanish Romani (gypsies) with autosomal recessive non-syndromic hearing loss.
AB  - Molecular testing for mutations in the gene encoding connexin-26 (GJB2) at the
      DFNB1 locus has become the standard of care for genetic diagnosis and counseling
      of autosomal recessive non-syndromic hearing impairment (ARNSHI). The spectrum of
      mutations in GJB2 varies considerably among the populations, different alleles
      predominating in different ethnic groups. A cohort of 34 families of Spanish
      Romani (gypsies) with ARNSHI was screened for mutations in GJB2. We found that
      DFNB1 deafness accounts for 50% of all ARNSHI in Spanish gypsies. The
      predominating allele is W24X (79% of the DFNB1 alleles), and 35delG is the second
      most common allele (17%). An allele-specific PCR test was developed for the
      detection of the W24X mutation. By using this test, carrier frequencies were
      determined in two sample groups of gypsies from different Spanish regions
      (Andalusia and Catalonia), being 4% and 0%, respectively. Haplotype analysis for
      microsatellite markers closely flanking the GJB2 gene revealed five different
      haplotypes associated with the W24X mutation, all sharing the same allele from
      marker D13S141, suggesting that a founder effect for this mutation is responsible
      for its high prevalence among Spanish gypsies.

PMID- 16088917
TI  - A microtubule associated protein (hNUDC) binds to the extracellular domain of
      thrombopoietin receptor (Mpl).
AB  - Human NUDC (hNUDC) was initially characterized as a nuclear migration protein
      based on the similarity of its C-terminus to that of fungal NUDC from Aspergillus
      nidulans. However, hNUDC is a 331 amino acid protein whereas fungal NUDC is 198
      amino acids in length. The extra N-terminal portion of hNUDC has no known
      function or homology to other proteins. In this study, we report the binding of
      hNUDC to the extracellular domain of the thrombopoietin receptor (Mpl) as
      detected by the yeast two-hybrid system, GST pull-down, and co
      immunoprecipitation. Our deletion analysis demonstrated that amino acids between
      positions 100 and 238 as the critical domain mediating the hNUDC and Mpl
      interactions as detected by the two-hybrid system and GST pull-down assay.
      Immunofluorescence staining of human megakaryocyte cells indicated that hNUDC and
      Mpl colocalized at all stages of megakaryocyte development. Substantial
      colocalization of hNUDC with microtubules was also detected around nuclei and
      elongated microtubular structures, especially in proplatelet extensions.

PMID- 16088918
TI  - Malaria-suppressible expression of the anti-apoptotic triple GTPase mGIMAP8.
AB  - The IMAP/IAN family of AIG1-like GTPases is conserved among vertebrates and
      angiosperm plants and has been postulated to regulate apoptosis, particularly in
      context with diseases such as cancer, diabetes, and infections. The human genes
      were recently renamed as gimap for GTPase of the immunity associated protein
      (GIMAP) family. Here we extend this new nomenclature to the murine gimap gene
      family. All gimap genes of the mouse are clustered on chromosome 6B with eight
      functional members and one pseudogene. The mGIMAP proteins contain one GTP
      binding site and display molecular masses between 33 and 38 kDa except for the
      very unusual 77 kDa mGIMAP8 protein, which is the first characterized protein
      containing three GTP-binding domains. Northern blot analysis revealed expression
      of mgimap8 predominantly in the thymus. The low expression level observed in the
      spleen was further suppressed by Plasmodium chabaudi malaria. Confocal laser
      scanning microscopy demonstrated localization of mGIMAP8 at ER, Golgi, and
      mitochondria. Overexpression of mGIMAP8 could significantly impair anisomycin
      induced activation of caspase 3. Our data support the view that mGIMAP8 exerts an
      anti-apoptotic effect in the immune system and is involved in responses to
      infections.

PMID- 16088919
TI  - ATP1A2 mutations in 11 families with familial hemiplegic migraine.
AB  - Familial hemiplegic migraine (FHM) is an autosomal dominant form of migraine with
      aura. The disease is caused by mutations of at least three genes among which two
      have been identified, CACNA1A and ATP1A2. Very few mutations have been identified
      so far in ATP1A2. We screened the coding sequence of ATP1A2 in 26 unrelated FHM
      probands in whom CACNA1A screening was negative. A total of eight different
      mutations were identified in 11 of the probands (41%), including six missense
      mutations, one small deletion leading to a frameshift, and one in frame deletion.
      All were novel mutations. Two mutations were recurrent, in three and two
      families, respectively. Genotyping of 94 relatives of these 11 probands
      identified 47 mutation carriers, among whom 36 were clinically affected.
      Sequencing of all 23 exons in an ethnically matched panel detected only one
      exonic coding polymorphism.

PMID- 16088920
TI  - Recurrence of Mowat-Wilson syndrome in siblings with the same proven mutation.
AB  - Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with
      distinctive facial features, microcephaly, epilepsy, and a variable spectrum of
      congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the
      corpus callosum, genitourinary abnormalities, and congenital heart disease.
      Heterozygous mutations or deletions involving the gene ZFHX1B (previously SIP1)
      [OMIM 605802] have recently been found to cause MWS. There have previously been
      no reports of a sibling recurrence of this syndrome. A brother and sister are
      described with clinical features of MWS, where both have the same truncating
      mutation in exon 8 of ZFHX1B. As their parents are phenotypically normal and do
      not have the mutation in lymphocyte-derived DNA, the most likely explanation is
      germ-line mosaicism.

PMID- 16088921
TI  - Meier-Gorlin (ear-patella-short stature) syndrome: growth hormone deficiency and
      previously unrecognized findings.

PMID- 16088922
TI  - SALL1 mutation analysis in Townes-Brocks syndrome: twelve novel mutations and
      expansion of the phenotype.
AB  - Townes-Brocks syndrome is an autosomal dominantly inherited disorder, which
      comprises multiple birth defects including renal, ear, anal, and limb
      malformations. TBS has been shown to result from mutations in SALL1, a human gene
      related to the developmental regulator SAL of Drosophila melanogaster. The SALL1
      gene product is a zinc finger protein thought to act as a transcription factor.
      It contains four highly conserved, evenly distributed C2H2 double zinc finger
      domains. A single C2H2 motif is attached to the second domain, and at the amino
      terminus SALL1 contains a C2HC motif. Most mutations causing TBS are clustered in
      the N-terminal third of the SALL1 coding region and result in the production of
      truncated proteins containing only one or none of the C2H2 domains and the N
      terminal transcriptional repressor domain of SALL1. Twenty-three SALL1 mutations
      were reported prior to this work, 22 of which are located in exon 2, 5' of the
      second double zinc finger-encoding region. Here we present 12 novel mutations in
      SALL1 associated with Townes-Brocks syndrome in 13 unrelated families. These
      include three nonsense mutations, three short insertions and six short deletions.
      Thus the number of SALL1 mutations increases to 35. Rare phenotypical features
      among mutation positive patients include hypothyroidism, vaginal aplasia with
      bifid uterus, cryptorchidism, bifid scrotum without hypospadia scrotalis,
      unilateral chorioretinal coloboma with loss of vision, dorsal hypoplasia of the
      corpus callosum, and umbilical hernia.

PMID- 16088923
TI  - Analysis of RPS19 in patients with cartilage-hair hypoplasia and severe anemia:
      preliminary results.

PMID- 16088924
TI  - Analytical approach to the MR signal.
AB  - In this work, an analytical evaluation of the MR signal is presented using the
      principle of reciprocity for any transmit and receive probe(s) with general
      geometrical structure(s). It is shown that the excitation of the spins cannot be
      explained using the principle of reciprocity in its standard form due to the
      asymmetry in the permeability tensor of the transverse magnetization. In the
      reception problem, the standard form of the principle of reciprocity is then
      utilized to calculate the NMR signal. As expected, the analysis shows that the
      strength of the NMR signal is a function of the receive coil's (fictitious)
      circularly polarized component of the field that poses an opposite sense of
      rotation to that corresponding with the excitation field, produced by the same
      coil, if it were to be used for excitation.

PMID- 16088925
TI  - Protein structure prediction with the UNRES force-field using Replica-Exchange
      Monte Carlo-with-Minimization; Comparison with MCM, CSA, and CFMC.
AB  - Two current methods of global optimization are coupled to produce the Replica
      Exchange method together with Monte Carlo-with-Minimization (REMCM). Its
      performance is compared with each separate component and with other global
      optimization techniques. REMCM was applied to search the conformational space of
      coarse grain protein systems described by the UNRES force field. The method
      consists of several noninteracting copies of Monte Carlo simulation, and
      minimization was used after every perturbation to enhance the sampling of low
      energy conformations. REMCM was applied to five proteins of different topology,
      and the results were compared to those from other optimization methods, namely
      Monte Carlo-with-Minimization (MCM), Conformational Space Annealing (CSA), and
      Conformational Family Monte Carlo (CFMC). REMCM located global minima for four
      proteins faster and more consistently than either MCM or CFMC, and it converged
      faster than CSA for three of the five proteins tested. A performance comparison
      was also carried out between REMCM and the traditional Replica Exchange method
      (REM) for one protein, with REMCM showing a significant improvement. Moreover,
      because of its simplicity, REMCM was easy to implement, thereby offering an
      alternative to other global optimization methods used in protein structure
      prediction.

PMID- 16088926
TI  - CH/pi interactions involving aromatic amino acids: refinement of the CHARMM
      tryptophan force field.
AB  - High-level ab initio calculations have been carried out to study weak CH/pi
      interactions and as a check of the CHARMM force field for aromatic amino acids.
      Comparisons with published data indicate that the MP2/cc-pVTZ level of theory is
      suitable for calculations of CH/pi interaction, including the T-shape benzene
      dimer. This level of theory was, therefore, applied to investigate CH/pi
      interactions between ethene or cis-2-butene and benzene in a variety of
      orientations. In addition, complexes between ethene and a series of model
      compounds (toluene, methylindole and p-cresol) representing the aromatic amino
      acids were studied motivated by the presence of CH/pi interactions in biological
      systems. Ab initio binding energies were compared to the binding energies
      obtained with the CHARMM22 force field. In the majority of orientations, CHARMM22
      reproduces the preferred binding modes, with excellent agreement for the benzene
      dimer. Small discrepancies found in the calculations involving methylindole along
      with a survey of published thermodynamic data for the aromatic amino acids
      prompted additional optimization of the tryptophan force field. Partial atomic
      charges, Lennard-Jones parameters, and force constants were improved to obtain
      better intra- and intermolecular properties, with significant improvements
      obtained in the reproduction of experimental heats of sublimation for indole and
      free energies of aqueous solvation for methylindole.

PMID- 16088927
TI  - Is there an increased birth defect risk to children born to offspring of first
      cousin parents?

PMID- 16088928
TI  - An augmented effective core potential basis set for the calculation of molecular
      polarizabilities.
AB  - Calculations of molecular polarizabilities require basis sets capable of
      accurately describing the responses of the electrons to an external perturbation.
      Unfortunately, basis sets that yield suitable quantitative results have
      traditionally been all-electron sets with large numbers of primitives, making
      their use computationally intractable even for moderately sized systems. We
      present a systematic augmentation of the effective core potential basis set of
      Stevens et al. [J Chem Phys 81, 12 (1984), Can J Chem 70, 612 (1992)] for 39 main
      group elements based on the procedure used to construct diffuse and polarization
      functions in the well-known Sadlej basis sets [Collec Czech Chem Comm 53, 1995
      (1988)]. Representative calculations have been performed and we have shown that
      results to within 1% of all-electron calculations using the Sadlej basis set can
      be obtained for <1-35% of the computational cost using this new basis set.

PMID- 16088929
TI  - Molecular analysis of the HEXA gene in Italian patients with infantile and late
      onset Tay-Sachs disease: detection of fourteen novel alleles.
AB  - Tay-Sachs disease (TSD) is a recessively inherited disorder caused by the
      hexosaminidase A deficiency. We report the molecular characterization performed
      on 31 Italian patients, 22 with the infantile, acute form of TSD and nine
      patients with the subacute juvenile form, biochemically classified as B1 Variant.
      Of the 29 different alleles identified, fourteen were due to 15 novel mutations,
      two being in-cis on a new complex allele. The new alleles caused four
      frameshifts, three premature stop codons, three amino acid changes, two amino
      acid deletions and two splicing alterations. As previously reported, the c.533G>A
      (p.R178H) mutation was present either in homozygosity or as compound
      heterozygote, in all the patients with the late onset TSD form (B1 Variant); the
      allele frequency in this group is discussed by comparison with that found in
      infantile TSD.

PMID- 16088930
TI  - An MCA/MR syndrome with hypocholesterolemia due to familial
      hypobetalipoproteinemia: report of a second patient with Nguyen syndrome.
AB  - [Nguyen et al. (2003); Am J Med Genet 121A: 109-112] reported a boy with severe
      hypocholesterolemia due to autosomal dominant hypobetalipoproteinemia (ADBHL)
      associated with severe growth retardation, mental deficiency, epicanthal folds, a
      short nose with low nasal bridge and anteverted nares and bilateral partial
      cutaneous syndactyly of toes 2 and 3. Many of these manifestations resembled
      those in a mild form of Smith-Lemli-Opitz syndrome (SLOS). We report on a 13-year
      old boy with ADHBL, who manifested a SLOS-like phenotype, including mental
      retardation and a characteristic face, similar to that of a patient reported by
      [Nguyen et al. (2003); Am J Med Genet 121A: 109-112]. Our patient supports the
      hypothesis by [Nguyen et al. (2003); Am J Med Genet 121A: 109-112] that ADHBL
      induced cholesterol deficiency has a significant effect on morphogenesis during
      embryogenesis, although additional genetic or environmental factors may be
      required to develop an SLOS-like phenotype in individuals with ADHLB. This is a
      second case of Nguyen syndrome.

PMID- 16088931
TI  - Molecular markers in malignant cutaneous melanoma: gift horse or one-trick pony?
AB  - The management of malignant cutaneous melanoma is problematic. Current clinical
      prognostic factors do not adequately predict disease recurrence and overall
      survival in a significant subset of patients. Adjuvant therapies for melanoma are
      notoriously toxic and associated with significant morbidity. Furthermore, it has
      been difficult to predict which patients will respond best to these treatments,
      if at all. DNA and RNA biomarkers have been developed to help overcome these
      problems. Biomarkers have been shown to upstage patients with melanoma, but are
      the assays sensitive and specific enough for clinical use as predictors of
      disease outcome or treatment response? We review our experience with DNA and RNA
      biomarkers in terms of their prognostic and predictive capabilities in malignant
      melanoma and outline their likely role in the future of melanoma staging,
      surveillance, and treatment.

PMID- 16088932
TI  - Upregulation of Daxx mediates apoptosis in response to oxidative stress.
AB  - Oxidative stress induces apoptosis in a variety of cell types by as yet unclear
      signaling mechanisms. The Daxx protein is reportedly involved in apoptosis
      through its interactions with Fas, transforming growth factor-beta receptor, and
      promyelocytic leukemia protein (PML). Here, we explored the possible roles of
      Daxx in oxidative stress-induced apoptosis. We found that both the mRNA and
      protein levels of Daxx markedly increased when cells underwent apoptosis after
      H2O2 treatment. Pretreatment with the cell-permeable antioxidant, N-acetyl
      cysteine, prevented cells from H2O2-induced Daxx upregulation and subsequent
      apoptosis, indicating that the endogenous oxidant regulated Daxx expression.
      Furthermore, suppression of endogenous Daxx expression by antisense
      oligonucleotide technology inhibited oxidative stress-induced apoptosis in HeLa
      cells. Taken together, these results suggest that Daxx acts as an intermediary
      messenger of pro-apoptotic signals triggered by oxidative stress.

PMID- 16088933
TI  - DHPLC analysis of patients with Nevoid Basal Cell Carcinoma Syndrome reveals
      novel PTCH missense mutations in the sterol-sensing domain.
AB  - Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal dominant disorder
      characterised by multiple basal cell carcinomas, palmar and plantar pitting,
      odontogenic keratocysts of the jaws and bilamellar calcification of the falx.
      Mutations in the PTCH gene are responsible for NBCCS but most studies have found
      mutations in less than half of the cases tested. We used denaturing high
      performance liquid chromatography (DHPLC) to screen for PTCH mutations in 28
      NBCCS cases, most of whom had been previously evaluated by single stranded
      conformation polymorphism analysis but found to be negative. Protein truncating
      (n = 10) and missense or indel (n = 4) mutations were found in 14/28 (50%) cases
      and one additional case carried an unclassified variant, c.2777G>C. Thirteen of
      the variants were novel. The mutation frequency was similar in inherited and de
      novo cases. Three of the missense and indel mutations were in the sterol-sensing
      domain, and one was in the sixth transmembrane domain.

PMID- 16088934
TI  - Electromagnetic perspective on the operation of RF coils at 1.5-11.7 Tesla.
AB  - In this work experimental and numerical studies of the MR signal were performed
      at frequencies ranging from 64 MHz to 485 MHz, utilizing three different MRI
      coils: a single-strut transverse electromagnetic (TEM)-based coil, a TEM
      resonator, and a high-pass birdcage coil. The experimental analyses were
      conducted using 1.5 and 8 Tesla whole-body systems and volume RF head coils. The
      simulation data were obtained utilizing an in-house-developed finite difference
      time domain (FDTD) model. Pertinent data from the numerical and experimental
      setups were compared, and a remarkable agreement between the two methods was
      found that clearly demonstrates the effectiveness of the FDTD method when it is
      applied rigorously. The numerical and experimental studies demonstrate the
      complexity of the electromagnetic (EM) fields and their role in the MR signal.
      These studies also reveal unique similarities and differences between the
      transmit and receive field distributions at various field strengths. Finally, for
      ultra high-field operations, it was demonstrated mathematically, numerically, and
      experimentally that highly asymmetric inhomogeneous images can be acquired even
      for linear excitation, symmetrical load geometries, and symmetrical load
      positioning within the coil.

PMID- 16088935
TI  - De novo Alu element insertions targeted to a sequence common to the BRCA1 and
      BRCA2 genes.
AB  - Linkage analysis suggests that mutations in the BRCA1 and BRCA2 genes are
      responsible for cancer predisposition in more than 80% of the families with high
      incidence of breast/ovarian cancer. However, pathogenic mutations in the BRCA1/2
      genes are generally identified in much less than half of the families
      investigated in a diagnostic setting with the currently used PCR-based screening
      protocols. Here we report the identification of two different de novo Alu element
      insertions within the BRCA1/2 coding sequences in three out of the 50 families in
      which we found a cancer predisposing mutation, suggesting that this type of
      mutation is much more common than suggested by their occurrence in mutation
      databases. The Alu insertion in the BRCA2 gene resulted in the removal of the
      targeted exon from the corresponding mRNA molecule. Unexpectedly the Target Site
      Duplications generated by both Alu element insertions contained a specific 9 bp
      long segment, which might eventually serve as a recognition site for the
      transposition machinery. Finally, in contrast to the disease causing Alu
      insertions reported to date, the transposon identified in the BRCA1 gene does not
      belong to a "young" AluY but to an AluS subfamily, indicating that some of these
      "old" Alu elements, which are supposed to be non-functional fossil relics, are
      still able to retrotranspose in vivo.

PMID- 16088936
TI  - Marked decrease in specific activity contributes to disease phenotype in two
      human glucose 6-phosphate dehydrogenase mutants, G6PD(Union) and G6PD(Andalus).
AB  - Clones overexpressing clinical glucose 6-phosphate dehydrogenase (G6PD) mutants
      Union (c.1360C>T/p.Arg454Cys) and Andalus (c.1361G>A/p.Arg454His), have been
      constructed. These abolish a salt bridge between Arg454 and Asp 286. One mutant
      is reportedly a Class II clinical variant and the other a Class I. Kinetic
      studies of the purified proteins reveal that, for both mutants, kcat is about 10
      fold decreased, thus giving a 90% decrease in the WHO assay, and also presumably
      under physiological conditions. In contrast with unfavourable changes in Vmax for
      both mutants, Km values for both G6P and NADP+ are decreased approximately 5
      fold. Measurements with alternative substrates confirm that G6PD Union, like the
      wild-type enzyme, follows a rapid-equilibrium random-order mechanism, allowing
      calculation of enzyme-substrate dissociation constants from initial-rate
      parameters. The mutations result in several-fold tighter binding of glucose 6
      phosphate to the free enzyme. Binding, however, is clearly less productive than
      with normal enzyme. G6PD mutations are thought to cause haemolytic anaemia by
      compromising enzyme stability. Both these mutants indeed show somewhat decreased
      thermostability. However, at 37 degrees C and with NADP+, the stability
      differences are only moderate. Decreased catalytic efficiency clearly contributes
      to the disease phenotype of these two mutants, entirely accounting for reported
      decrease in leukocyte G6PD levels, though not for still lower levels in
      erythrocytes. Neither the kinetic nor the stability effects appear to justify the
      different clinical classification of these mutations.

PMID- 16088937
TI  - Prospects: histone deacetylase inhibitors.
AB  - Histone deacetylase (HDAC), inhibitors represent a new class of targeted anti
      cancer agents. Several of these compounds are in clinical trials with significant
      activity against a spectrum of both hematologic and solid tumors at doses that
      are well tolerated by the patients. The HDAC inhibitors are a structurally
      diverse group of molecules that can induce growth arrest, differentiation,
      apoptosis, and autophagocytic cell death of cancer cells. While the base sequence
      of DNA provides the genetic code for proteins, the expression of genes is
      regulated, in large part, by the structure of the chromatin proteins around which
      the DNA is wrapped (epigenetic gene regulation). The acetylation and
      deacetylation of the lysines in the tails of the core histones, among the most
      extensively studied aspects of chromatin structure, is controlled by the action
      of two families of enzymes, histone deacetylases (HDACs) and histone
      acetyltransferases (HATs). Protein components of transcription factor complexes
      and many other non-histone proteins are also substrates for HDACs and HATs. The
      structure and activity of these non-histone proteins may be altered by
      acetylation/deacetylation with consequent effects on various cell functions
      including gene expression, cell cycle progression, and cell death pathways. This
      review focuses on several key questions with respect to the mechanism of action
      of HDACi, including, what are the different cell phenotypes induced by HDACi, why
      are normal cells compared to transformed cells relatively resistant to HDACi
      induced cell death, why are certain tumors more responsive to HDACi than others,
      and what is the basis of the selectivity of HDACi in altering gene expression.
      The answers to these questions will have therapeutic importance since we will
      identify targets for enhancing the efficacy and safety of HDACi.

PMID- 16088938
TI  - PIKE/nuclear PI 3-kinase signaling in preventing programmed cell death.
AB  - PI 3-kinase enhancer (PIKE) is a nuclear GTPase that enhances PI 3-kinase (PI3K)
      activity. Nerve growth factor (NGF) treatment leads to PIKE activation by
      triggering the nuclear translocation of PLC-gamma1, which acts as a physiological
      guanine nucleotide exchange factor (GEF) for PIKE. PI3K occurs in the nuclei of a
      broad range of cell types, and various stimuli elicit PI3K nuclear translocation.
      While cytoplasmic PI3K has been well characterized, little is known about the
      biological function of nuclear PI3K. Surprisingly, nuclei from 30 min NGF-treated
      PC12 cells are resistant to DNA fragmentation initiated by the activated cell
      free apoptosome, and both PIKE and nuclear PI3K are sufficient and necessary for
      this effect. Moreover, pretreatment of the control nucleus with PI(3,4,5)P3 alone
      mimics the anti-apoptotic activity of NGF by selectively preventing apoptosis,
      for which nuclear Akt is required but not sufficient. Recently, a nuclear
      PI(3,4,5)P3 receptor, nucleophosmin/B23, has been identified from NGF-treated
      PC12 nuclear extract. PI(3,4,5)P3/B23 complex mediates the anti-apoptotic effects
      of NGF by inhibiting DNA fragmentation activity of caspase-activated DNase (CAD).
      Thus, PI(3,4,5)P3/B23 complex and nuclear Akt effectors might coordinately
      mediate PIKE/nuclear PI3K signaling in promoting cell survival by NGF.

PMID- 16088939
TI  - Nuclear inositol lipid metabolism: more than just second messenger generation?
AB  - A distinct polyphosphoinositide cycle is present in the nucleus, and growing
      evidence suggests its importance in DNA replication, gene transcription, and
      apoptosis. Even though it was initially thought that nuclear inositol lipids
      would function as a source for second messengers, recent findings strongly
      indicate that lipids present in the nucleus also fulfil other roles. The scope of
      this review is to highlight the most intriguing advances made in the field over
      the last few years, such as the possibility that nuclear phosphatidylinositol
      (4,5) bisphosphate is involved in maintaining chromatin in a transcriptionally
      active conformation, the new emerging roles for intranuclear phosphatidylinositol
      (3,4,5) trisphosphate and phosphoinositide 3-kinase, and the evidence which
      suggests a tight relationship between a decreased level of nuclear
      phosphoinositide specific phospholipase C-beta1 and the evolution of
      myelodisplastic syndrome into acute myeloid leukemia.

PMID- 16088940
TI  - TGF-beta control of cell proliferation.
AB  - This article focuses on recent findings that the type V TGF-beta receptor (TbetaR
      V), which co-expresses with other TGF-beta receptors (TbetaR-I, TbetaR-II, and
      TbetaR-III) in all normal cell types studied, is involved in growth inhibition by
      IGFBP-3 and TGF-beta and that TGF-beta activity is regulated by two distinct
      endocytic pathways (clathrin- and caveolar/lipid-raft-mediated). TGF-beta is a
      potent growth inhibitor for most cell types, including epithelial and endothelial
      cells. The signaling by which TGF-beta controls cell proliferation is not well
      understood. Many lines of evidence indicate that other signaling pathways, in
      addition to the prominent TbetaR-I/TbetaR-II/Smad2/3/4 signaling cascade, are
      required for mediating TGF-beta-induced growth inhibition. Recent studies
      revealed that TbetaR-V, which is identical to LRP-1, mediates IGF-independent
      growth inhibition by IGFBP-3 and mediates TGF-beta-induced growth inhibition in
      concert with TbetaR-I and TbetaR-II. In addition, IRS proteins and a Ser/Thr
      specific protein phosphatase(s) are involved in the TbetaR-V-mediated growth
      inhibitory signaling cascade. The TbetaR-V signaling cascade appears to cross
      talk with the TbetaR-I/TbetaR-II, insulin receptor (IR), IGF-I receptor (IGF-IR),
      integrin and c-Met signaling cascades. Attenuation or loss of the TbetaR-V
      signaling cascade may enable carcinoma cells to escape from TGF-beta growth
      control and may contribute to the aggressiveness and invasiveness of these cells
      via promoting epithelial-to-mesenchymal transdifferentiation (EMT). Finally, the
      ratio of TGF-beta binding to TbetaR-II and TbetaR-I is a signal controlling TGF
      beta partitioning between two distinct endocytosis pathways and resultant TGF
      beta responsiveness. These recent studies have provided new insights into the
      molecular mechanisms underlying TGF-beta-induced cellular growth inhibition,
      cross-talk between the TbetaR-V and other signaling cascades, the signal that
      controls TGF-beta responsiveness and the role of TbetaR-V in tumorigenesis.

PMID- 16088941
TI  - Parathyroid hormone (PTH) and hematopoiesis: new support for some old
      observations.
AB  - Forty-seven years ago, the parathyroid hormone (PTH) in one injection of Lilly's
      old bovine parathyroid extract, PTE, was found to greatly increase the 30-day
      survival of heavily X-irradiated rats when given from 18 h before to as long as 3
      h after irradiation but no later. This was the first indication that PTH might
      stimulate hematopoiesis. Recent studies have confirmed the relation between PTH
      and hematopoiesis by showing that hPTH-(1-34)OH increases the size of the
      hematopoietic stem cell pool in mice. The peptide operates through a cyclic AMP
      mediated burst of Jagged 1 production in osteoblastic cells lining the stem
      cells' niches on trabecular bone surfaces. The osteoblastic cells' Jagged 1
      increases the hematopoietic stem cell pool by activating Notch receptors on
      attached stem cells. PTH-triggered cyclic AMP signals also directly stimulate the
      proliferation of the hematopoietic stem cells. However, the single PTH injection
      in the early experiments using PTE probably increased the survival of irradiated
      rats mainly by preventing the damaged hematopoietic progenitors from irreversibly
      initiating self-destructive apoptogenesis during the first 5 h after irradiation.
      It has also been shown that several daily injections of hPTH-(1-34)OH enable
      lethally irradiated mice to survive by stimulating the growth of transplanted
      normal bone marrow cells. If the osteogenic PTHs currently entering or on the
      verge of entering the market for treating osteoporosis can also drive
      hematopoiesis in humans as well as rodents, they could be potent tools for
      reducing the damage inflicted on bone marrow by cytotoxic cancer chemotherapeutic
      drugs and ionizing radiation.

PMID- 16088942
TI  - Localization of neuronal calcium sensor-1 at the adult and developing rat
      neuromuscular junction.
AB  - Neuronal calcium sensor (NCS-1; frequenin) is a calcium-binding protein involved
      in the regulation of neurotransmission in the central and peripheral nervous
      systems from insects to vertebrates. This study reports the localization of NCS-1
      immunoreactivity, by Western blotting and immunohistochemistry, at the adult and
      developing postnatal rat neuromuscular junction. Our confocal immunofluorescence
      results on the whole-mount muscle and on semithin cross-sections are indicative
      of the localization of NCS-1 to motor axon terminals. There is no evidence of
      immunoreactivity in the postsynaptic side of the neuromuscular junctions or
      teloglial Schwann cells. These results suggest that NCS-1 is involved in the
      formation and function of presynaptic nerve terminal part of the neuromuscular
      junction during synaptogenesis and in adult mammals.

PMID- 16088943
TI  - PTEN enters the nucleus by diffusion.
AB  - Despite much evidence for phosphatidylinositol phosphate (PIP)-triggered
      signaling pathways in the nucleus, there is little understanding of how the
      levels and activities of these proteins are regulated. As a first step to
      elucidating this problem, we determined whether phosphatase and tensin homolog
      deleted on chromosome 10 (PTEN) enters the nucleus by passive diffusion or active
      transport. We expressed various PTEN fusion proteins in tsBN2, HeLa, LNCaP, and
      U87MG cells and determined that the largest PTEN fusion proteins showed little or
      no nuclear localization. Because diffusion through nuclear pores is limited to
      proteins of 60,000 Da or less, this suggests that nuclear translocation of PTEN
      occurs via diffusion. We examined PTEN mutants, seeking to identify a nuclear
      localization signal (NLS) for PTEN. Mutation of K13 and R14 decreased nuclear
      localization, but these amino acids do not appear to be part of an NLS. We used
      fluorescence recovery after photobleaching (FRAP) to demonstrate that GFP-PTEN
      can passively pass through nuclear pores. Diffusion in the cytoplasm is retarded
      for the PTEN mutants that show reduced nuclear localization. We conclude that
      PTEN enters the nucleus by diffusion. In addition, sequestration of PTEN in the
      cytoplasm likely limits PTEN nuclear translocation.

PMID- 16088944
TI  - E2F1 induces cell death, calpain activation, and MDMX degradation in a
      transcription independent manner implicating a novel role for E2F1 in neuronal
      loss in SIV encephalitis.
AB  - The E2F1 transcription factor can initiate proliferation or apoptosis, the latter
      by both transcription-dependent and -independent mechanisms. Recently, an E2F1
      mutant lacking the DNA binding domain, E2F1(180-437), has been implicated in
      degradation of MDMX and MDM2 proteins via lysosomal proteases. MDM proteins block
      p53 dependent apoptosis by directly inhibiting p53 stability and function. Here
      we demonstrate E2F1(180-437) induces death in HEK293 cells independent of E2F1
      transcriptional activation and p53 stabilization. E2F1(180-437) elevates the
      activity of the calcium-activated protease, calpain, which is required for E2F1
      induced proteolysis of MDMX and E2F1 induced cell loss. To determine if E2F1
      could be activating proteolysis via calpains in neurodegeneration, we examined
      MDMX immunofluorescence in simian immunodeficiency virus encephalitis (SIVE). We
      found a reciprocal relationship between E2F1 and MDMX staining: in SIVE where
      E2F1 immunostaining is increased, MDMX is decreased, while in controls where E2F1
      immunostaining is low, MDMX is high. Together these experiments support a new
      function for E2F1 in the activation of calpain proteases and suggest a role for
      this pathway in SIVE.

PMID- 16088945
TI  - Induction of osteogenic differentiation of human mesenchymal stem cells by
      histone deacetylase inhibitors.
AB  - Valproic acid (VPA) has been used as an anticonvulsant agent for the treatment of
      epilepsy, as well as a mood stabilizer for the treatment of bipolar disorder, for
      several decades. The mechanism of action for these effects remains to be
      elucidated and is most likely multifactorial. Recently, VPA has been reported to
      inhibit histone deacetylase (HDAC) and HDAC has been reported to play roles in
      differentiation of mammalian cells. In this study, the effects of HDAC inhibitors
      on differentiation and proliferation of human adipose tissue-derived stromal
      cells (hADSC) and bone marrow stromal cells (hBMSC) were determined. VPA
      increased osteogenic differentiation in a dose dependent manner. The pretreatment
      of VPA before induction of differentiation also showed stimulatory effects on
      osteogenic differentiation of hMSC. Trichostatin A (TSA), another HDAC inhibitor,
      also increased osteogenic differentiation, whereas valpromide (VPM), a structural
      analog of VPA which does not possess HDAC inhibitory effects, did not show any
      effect on osteogenic differentiation on hADSC. RT-PCR and Real-time PCR analysis
      revealed that VPA treatment increased osterix, osteopontin, BMP-2, and Runx2
      expression. The addition of noggin inhibited VPA-induced potentiation of
      osteogenic differentiation. VPA inhibited proliferation of hADSC and hBMSC. Our
      results suggest that VPA enhance osteogenic differentiation, probably due to
      inhibition of HDAC, and could be useful for in vivo bone engineering using hMSC.

PMID- 16088946
TI  - Inhibitory effects of thioredoxin reductase antisense RNA on the growth of human
      hepatocellular carcinoma cells.
AB  - Thioredoxin reductase (TrxR) in conjunction with thioredoxin (Trx) is a
      ubiquitous intracellular oxidoreductase system with antioxidant and redox
      regulatory roles. In some human tumors, the thioredoxin system is found
      overexpressed. We have used an antisense approach to investigate whether
      inhibition of TrxR overexpression can suppress the growth of human hepatocellular
      carcinoma SMMC-7721 cells. TrxR cDNA fragment was inserted in the antisense
      direction into pcDNA3.1/myc-His and SMMC-7721 cells were stably transfected with
      the plasmid construct. The results showed that TrxR antisense RNA could
      significantly reduce TrxR mRNA level and activity, and suppress the growth of
      SMMC-7721 cells. Cell-cycle analysis showed G2/M phase arrest in SMMC-7721 cells
      transfected with TrxR antisense plasmid. TrxR antisense RNA could significantly
      increase p53 mRNA level and decrease Bcl-2 mRNA level by reverse transcriptase
      polymerase chain reaction (RT-PCR). Furthermore a significant decrease in human
      telomerase reverse transcriptase (hTERT) mRNA level was found in SMMC-7721 cells
      transfected with TrxR antisense plasmid. Flow cytometry and telomere fluorescence
      in situ hybridization (Flow FISH) showed that TrxR antisense RNA could
      significantly reduce the telomere fluorescence in SMMC-7721 cells. The results
      suggested that TrxR antisene RNA inhibited the growth of SMMC-7721 cells through
      an accumulation of cell cycle at G2/M phase, an increase in p53 mRNA level and a
      reduction in telomere fluorescence and Bcl-2, hTERT mRNA levels.

PMID- 16088947
TI  - Fluoxetine treatment of prepubescent rats produces a selective functional
      reduction in the 5-HT2A receptor-mediated stimulation of oxytocin.
AB  - Various childhood mood disorders are being treated with serotonin selective
      reuptake inhibitors (SSRIs) such as fluoxetine (Prozac(R)), yet limited data are
      available on their effects on serotonergic systems prior to maturation. This
      study investigated the effects of chronic fluoxetine treatment on 5-HT2A
      serotonin receptor-mediated neuroendocrine responses in young male rats.
      Prepubescent male rats were treated with saline or fluoxetine (10 mg/kg/day,
      i.p.) for 14 days, a treatment regimen producing maximal changes in postsynaptic
      5-HT2A function in adults. Eighteen hours post-treatment, the rats received
      saline or increasing doses (0.5, 2.0, or 5.0 mg/kg, i.p.) of the 5-HT2 receptor
      agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl ((+/-)-DOI).
      Trunk blood was obtained to determine changes in oxytocin, ACTH, corticosterone,
      and renin responses. Fluoxetine produced a small ( approximately 6%) but
      significant reduction in body weight gain, but no changes were observed in basal
      hormone levels. In both saline- and fluoxetine-treated rats, (+/-)-DOI increased
      plasma oxytocin levels in a dose-dependent manner. However, the magnitude of the
      oxytocin responses to all doses of (+/-)-DOI were markedly attenuated (
      approximately 50%) in the fluoxetine-treated rats, indicating a functional
      reduction in the E(max) of 5-HT(2A) receptor-mediated oxytocin responses. In
      contrast, fluoxetine did not alter the (+/-)-DOI-induced increases in plasma
      ACTH, corticosterone, or renin. These data provide the first demonstration of
      selective neuroadaptive responses in 55-HT2A serotonin receptor function due to
      prepubescent treatment with fluoxetine. These data may be clinically relevant
      with respect to the use of selective serotonin reuptake inhibitors in children
      and adolescents.

PMID- 16088949
TI  - Decreased cell proliferation in the dentate gyrus of rats after repeated
      administration of cocaine.
AB  - Cell proliferation in the dentate gyrus of hippocampus was assessed using in vivo
      labeling with 5-bromo-2'-deoxyuridine (BrdU) in adult rats that were administered
      cocaine (20 mg/kg) for 14 consecutive days. Rats showed increased stereotypy at a
      challenge dose of cocaine after 1 week of withdrawal, suggesting the acquisition
      of behavioral sensitization. Twenty-four hours after final injection of
      repetitive cocaine administration, a 26% decrease in BrdU-positive cells was
      observed, compared with control rats. However, this returned to control level
      within 1 week. No differences were observed in rats that received a single
      injection of cocaine. Differentiation of newly formed cells was not influenced.
      These data imply that the regulation of hippocampal cell proliferation by cocaine
      may be involved in the development of certain symptoms of addiction, such as
      cognitive impairment and acquisition of behavioral sensitization.

PMID- 16088948
TI  - Induction of striatal pre- and postsynaptic damage by methamphetamine requires
      the dopamine receptors.
AB  - Methamphetamine (METH) is a psychostimulant that induces excessive release of
      dopamine (DA) in the striatum. In this study we have assessed the role of DA D1
      and D2 receptors (D1R and D2R) on striatal METH-induced apoptosis and depletion
      of DA-terminal markers. Male mice were given one i.p. injection of METH (30
      mg/kg). Apoptosis was assessed at 24 h, and DA-terminal marker depletion 3 days,
      after METH. A single toxic dose of METH induced apoptosis in approximately 10-13%
      of striatal neurons. This was completely prevented by pretreatment (30 min before
      METH) with either the D1R antagonist SCH-23390 (0.1 mg/kg) or the D2R antagonist
      raclopride (1 mg/kg). The same dose of METH induced depletion of DA transporter
      sites up to 61, 56, 71, and 69% in dorsal-medial, ventral-medial, dorsal-lateral,
      and ventral-lateral striatum, respectively, relative to vehicle-injected
      controls. Similarly, METH induced depletion of TH protein levels up to 80, 72,
      87, and 90% in those respective quadrants. METH induced the expression of glial
      fibrillary acidic protein throughout the striatum. All these neurochemical
      changes were significantly attenuated by pretreatment with SCH-23390 (0.1 mg/kg)
      or raclopride (1 mg/kg). However, pretreatment with either raclopride or SCH
      23390 did not prevent METH-induced hyperthermia in mice. These data demonstrate
      that the induction by METH of both striatal apoptosis and DA-terminal damage
      requires the activity of the postsynaptic DA receptors in the mouse brain.
      Moreover, since blockade of either receptor subtype protected from METH, the
      activity of both DA receptor subtypes is required for the induction of toxicity
      by METH in the striatum.

PMID- 16088950
TI  - Characterization of the spontaneous and gripping-induced immobility episodes on
      taiep rats.
AB  - In 1989, we described a new autosomic-recessive myelin-mutant rat that develops a
      progressive motor syndrome characterized by tremor, ataxia, immobility episodes
      (IEs), epilepsy, and paralysis. taiep is the acronym of these symptoms. The rat
      developed a hypomyelination, followed by demyelination. At an age of 7-8 months,
      taiep rats developed IEs, characterized electroencephalographically by REM sleep
      like cortical activity. In our study, we analyzed the ontogeny of gripping
      induced IEs between 5 and 18 months, their dependence to light-dark changes,
      sexual dimorphism, and susceptibility to mild stress. Our results showed that IEs
      start at an age of 6.5 months, with a peak frequency between 8.5 and 9.5 months.
      IEs have two peaks, one in the morning (0800-1000 h) and a second peak in the
      middle of the night (2300-0100 h). Spontaneous IEs showed an even distribution
      with a mean of 3 IEs every 2 h. IEs are sexually dimorphic being more common in
      male rats. The IEs can be induced by gripping the rat by the tail or the thorax,
      but most of the IEs were produced by gripping the tail. Mild stress produced by
      i.p. injection of physiological saline significantly decreased IEs. These results
      suggested that IEs are dependent on several biological variables, which are
      caused by hypomyelination, followed by demyelization, which causes alterations in
      the brainstem and hypothalamic mechanisms responsible for the sleep-wake cycle
      regulation, producing emergence of REM sleep-like behavior during awake periods.

PMID- 16088951
TI  - Antiparkinson concentrations of pramipexole and PHNO occupy dopamine D2(high) and
      D3(high) receptors.
AB  - Because the high-affinity state of dopamine D2 receptors, D2(High), is the
      functional state of D2, and because the proportion of D2 receptors in the high
      affinity state correlates with dopamine behavioral supersensitivity, the present
      study was designed to determine the affinities of antiparkinson dopamine agonists
      at the D2(High) site by means of competition with [3H]domperidone. In contrast to
      [125I]iodosulpride or [3H]spiperone, which are not sensitive to low
      concentrations of dopamine agonists, [3H]domperidone readily reveals dissociation
      constants (K(i)) for antiparkinson agonists at D2(High) and D3(High) receptors.
      The K(i) values for the human cloned D2(High) and D3(High) receptors,
      respectively, were 19 and 9 nM for pramipexole, 0.24 and 0.6 nM for +PHNO, 0.7
      and 1.3 nM for bromocriptine, 0.5 and 2.6 nM for apomorphine, and 0.09 and 0.25
      nM for (-)N-propylnorapomorphine. After correcting for the fraction of drug bound
      to plasma proteins, the known clinical concentrations in plasma or plasma water
      of these drugs, including pramipexole and +PHNO, are sufficient to occupy and
      activate the high-affinity state of D2, D2(High), in treating Parkinson's
      disease. The D3(High) receptors are less selectively occupied by +PHNO,
      bromocriptine, apomorphine, and -NPA.

PMID- 16088952
TI  - A comprehensive atlas of the topography of functional groups of the dopamine
      transporter.
AB  - The neuronal dopamine transporter (DAT) is a transmembrane transporter that
      clears DA from the synaptic cleft. Knowledge of DAT functional group topography
      is a prerequisite for understanding the molecular basis of transporter function,
      the actions of psychostimulant drugs, and mechanisms of dopaminergic
      neurodegeneration. Information concerning the molecular interactions of drugs of
      abuse (such as cocaine, amphetamine, and methamphetamine) with the DAT at the
      functional group level may also aid in the development of compounds useful as
      therapeutic agents for the treatment of drug abuse. This review will provide a
      cumulative and comprehensive focus on the amino acid functional group topography
      of the rat and human DATs, as revealed by protein chemical modification and the
      techniques of site-directed mutagenesis. The results from these studies,
      represented mostly by site-directed mutagenesis, can be classified into several
      main categories: modifications without substantial affects on substrate
      transport, DAT membrane expression, or cocaine analog binding; those
      modifications which alter both substrate transport and cocaine analog binding;
      and those that affect DAT membrane expression. Finally, some modifications can
      selectively affect either substrate transport or cocaine analog binding. Taken
      together, these literature results show that domains for substrates and cocaine
      analogs are formed by interactions with multiple and sometimes distinct DAT
      functional groups.

PMID- 16088953
TI  - Extracts of retina and brain that excite afferent fibers innervating hair cells
      contain a compound related to hydroxyphenylglycine-N-carbamoyl.
AB  - To identify new neurotransmitter and modulator candidates that might be important
      in transmission from sensory hair cells to afferent nerves, we examined extracts
      of neural tissue for compounds that excite afferent fibers innervating hair
      cells. Here, we describe the extraction and purification from retina and brain of
      a potent, unstable, excitatory compound with pharmacological activity similar to
      glutamate on afferent fibers innervating hair cells. This compound, however, was
      clearly distinguished from glutamate, other common amino acids, and known
      endogenous glutamate-receptor agonists. After derivatization and analysis by gas
      chromatography-mass spectrometry, the major compound found in highly purified
      neuroactive chromatographic fractions had the same gas chromatographic elution
      time and mass spectrum as the compound formed by derivatization of L-p
      hydroxyphenylglycine-N-carbamoyl. Hydroxyphenylglycine-N-carbamoyl, however, did
      not copurify with the neuroactive compound and was not neuroactive. We thus
      hypothesize that the detected compound was produced from a precursor,
      structurally related to L-p-hydroxyphenylglycine-N-carbamoyl, that was a major
      component of the neuroactive chromatographic fractions. Because several compounds
      related to hydroxyphenylglycine are known to act on glutamate receptors, such a
      compound is an interesting candidate to be an endogenous glutamate-receptor
      ligand in the mammalian nervous system.

PMID- 16088954
TI  - Isolation and identification of 1alpha-hydroxy-3-epi-vitamin D3, a potent
      suppressor of parathyroid hormone secretion.
AB  - Since our original demonstration of the metabolism of 1alpha,25(OH)2D3 into
      1alpha,25(OH)2-3-epi-D3 in human keratinocytes, there have been several reports
      indicating that epimerization of the 3 hydroxyl group of vitamin D compounds is a
      common metabolic process. Recent studies reported the metabolism of 25OHD3 and
      24(R),25(OH)2D3 into their respective C-3 epimers, indicating that the presence
      of 1alpha hydroxyl group is not necessary for the 3-epimerization of vitamin D
      compounds. To determine whether the presence of a 25 hydroxyl group is required
      for 3-epimerization of vitamin D compounds, we investigated the metabolism of
      1alphaOHD3, a non-25 hydroxylated vitamin D compound, in rat osteosarcoma cells
      (ROS 17/2.8). We noted metabolism of 1alphaOHD3 into a less polar metabolite
      which was unequivocally identified as 1alphaOH-3-epi-D3 using the techniques of
      HPLC, GC/MS, and 1H-NMR analysis. We also identified 1alphaOH-3-epi-D3 as a
      circulating metabolite in rats treated with pharmacological concentrations of
      1alphaOHD3. Thus, these results indicated that the presence of a 25 hydroxyl
      group is not required for 3-epimerization of vitamin D compounds. Furthermore,
      the results from the same studies also provided evidence to indicate that
      1alphaOH-3-epi-D3, like 1alphaOHD3, is hydroxylated at C-25. We then evaluated
      the biological activities of 1alphaOH-3-epi-D3. Treatment of normal rats every
      other day for 7 days with 2.5 nmol/kg of 1alphaOH-3-epi-D3 did not raise serum
      calcium, while the same dose of 1alphaOHD3 increased serum calcium by 3.39 +/-
      0.52 mg/dl. Interestingly, in the same rats which received 1alphaOH-3-epi-D3 we
      also noted a reduction in circulating PTH levels by 65 +/- 7%. This ability of
      1alphaOH-3-epi-D3 to suppress PTH levels in normal rats without altering serum
      calcium was further tested in rats with reduced renal function. The results
      indicated that the ED50 of 1alphaOH-3-epi-D3 for suppression of PTH was only
      slightly higher than that of 1alpha,25(OH)2D3, but that the threshold dose of the
      development of hypercalcemia (total serum Ca > 10.5 mg/dl) was nearly 80 times
      higher. These findings indicate that 1alphaOH-3-epi-D3 is a highly selective
      vitamin D analog with tremendous potential for treatment of secondary
      hyperparathyroidism in chronic renal failure patients.

PMID- 16088955
TI  - Stimulation of amphiregulin expression in osteoblastic cells by parathyroid
      hormone requires the protein kinase A and cAMP response element-binding protein
      signaling pathway.
AB  - Parathyroid hormone (PTH), an anabolic agent for bone metabolism, has profound
      effects on gene expression in the osteoblast. Recently, we identified that
      amphiregulin (AR), an EGF-like ligand, is an immediate early gene for PTH
      treatment and has an important role in bone metabolism. In the present report, by
      using different PTH peptide fragments, protein kinase activators, and inhibitors,
      we have demonstrated that PTH regulates amphiregulin in a cAMP-protein kinase A
      (PKA)-dependent manner both in vitro and in vivo. We found that the
      phosphorylation of cAMP-response element (CRE)-binding protein (CREB) preceded AR
      transcription after PTH treatment. Moreover, luciferase reporter assays revealed
      that the binding of phosphorylated CREB to a conserved CRE site in the AR
      promoter plays an important role in basal, PTH-induced, and prostaglandin E2
      (PGE2)-induced AR expression in osteoblastic cells. In summary, our data suggest
      that PTH-induced AR mRNA expression is mediated primarily through cAMP-PKA-CREB
      signaling.

PMID- 16088956
TI  - In vitro chondrogenesis of human synovium-derived mesenchymal stem cells: optimal
      condition and comparison with bone marrow-derived cells.
AB  - There are increasing reports that mesenchymal stem cells (MSCs) are present in
      various tissues other than bone marrow, including synovium. Here we investigated
      the optimal conditions for in vitro chondrogenesis of human synovium-derived MSCs
      and compared these cells with bone marrow-derived MSCs, especially in terms of
      their chondrogenesis potential. Synovium and bone marrow were harvested from six
      donors during knee operations for ligament injuries. Digested synovium cells or
      nucleated cells from bone marrow were expanded clonally. A pellet culture system
      was used for chondrogenesis, and the best combination of up to three cytokines of
      the seven assessed. Synovium-derived MSCs plated at a lower density expanded more
      rapidly. Contrary to previous reports, a combination of TGFbeta and dexamethasone
      was not sufficient to induce chondrogenesis. However, addition of BMP2 to TGFbeta
      and dexamethasone dramatically increased cartilage pellet size and the synthesis
      of cartilage matrix. The cartilage pellets were also analyzed by electron
      microscopy and immunohistology. DNA content per pellet decreased during
      chondrogenesis, indicating the pellet increased its size through the accumulation
      of newly synthesized extracellular matrix. Sequential chondrogenic gene
      expression was demonstrated by RT-PCR. Synovium-derived MSCs looked similar to
      the bone marrow-derived MSCs in their surface epitopes and proliferation
      potential; however, cartilage pellets from synovium were significantly larger
      than those from bone marrow in patient-matched comparisons. We demonstrated that
      the combination of TGFbeta, dexamethasone, and BMP2 was optimal for in vitro
      chondrogenesis of synovium-derived MSCs and that the synovium-derived MSCs have a
      greater chondrogenesis potential than bone marrow-derived MSCs.

PMID- 16088957
TI  - Interactions between the rabbit CSN1 gene and the nuclear matrix of stably
      transfected HC11 mammary epithelial cells vary with its level of expression.
AB  - The expression of casein genes is specific to the mammary gland and maximal
      during lactation. However, among the numerous mammary cell lines described so
      far, only a few express some casein genes. The regulatory regions of casein genes
      have been largely described but the mechanisms explaining the mammary specific
      expression of these genes, and their silencing in most mammary cell lines, have
      not yet been fully elucidated. To test the hypothesis that the nuclear location
      of the casein genes may affect their expression, we transfected HC11 mouse
      mammary cell line with a 100 kb DNA fragment surrounding the rabbit alpha S1
      casein gene. We derived stable clones which express or not the transfected rabbit
      casein gene, in the same cellular context, independently of the number of
      transgene copies. Metaphase spreads were prepared from the different clones and
      the transfected genes were localized. Unexpectedly, we observed that in the
      original HC11 cell line the number of chromosomes per metaphase spread is close
      to 80, suggesting that HC11 cells have undergone a duplication event, since the
      mouse karyotype is 2n = 40. In alpha S1 casein expressing cells, the expression
      level does not clearly correlate with a localization of the transfected DNA
      proximal to the centromeres or the telomeres. Analysis of the localization of the
      transfected DNA in nuclear halos allows us to conclude that when expressed,
      transfected DNA is more closely linked to the nuclear matrix. The next step will
      be to study the attachment of the endogenous casein gene in mammary nuclei during
      lactation.

PMID- 16088958
TI  - Differential regulation of cyclooxygenase 2 expression by small GTPases Ras,
      Rac1, and RhoA.
AB  - Cyclooxygenase 2 (COX-2) is an immediate early gene induced by a variety of
      stimuli and its expression is stimulated by individual activation of Ras or Rho
      GTPases. Here we investigate the role of coordinate activation of Ras and Rho
      GTPases in the induction of COX-2. Individual expression of constitutively active
      Ras, RhoA, or Rac1 was capable of stimulating COX-2 expression in NIH3T3 cells,
      but co-expression of constitutively active RhoA with either constitutively active
      Ras or Rac1 was required for full stimulation of COX-2 expression. Serum growth
      factors differentially activated Ras, RhoA, and Rac1, which correlated with the
      activation of Raf-1, ERK, and c-Jun as well as with induction of COX-2.
      Inhibition of Ras significantly blocked the activation of Raf-1, ERK, and c-Jun
      and the stimulation of COX-2 expression in response to serum. In contrast,
      inhibition of Rho family GTPases partially blocked serum induction of ERK
      activation but had little effects on COX-2 expression. Both inhibitors of MEK
      (PD098059) and JNK (SP600125) inhibited serum induction of COX-2. PD98059 only
      inhibited constitutively active Ras-induced COX-2 expression, while SP600125
      significantly inhibited both constitutively active Ras- and RhoA-induced COX-2
      expression. Together, our data suggest that constitutively active oncogenic Ras
      and Rho coordinately stimulate COX-2 expression whereas transient activation of
      Ras but not RhoA or Rac1 mediates the induction of COX-2 in response to serum.
      Furthermore, ERK and JNK activation are both required for serum- and oncogenic
      Ras-mediated COX-2 expression whereas only JNK activation is required for
      oncogenic RhoA-mediated stimulation of COX-2 expression.

PMID- 16088959
TI  - Low pH and Helicobacter pylori increase nuclear factor kappa B binding in gastric
      epithelial cells: a common pathway for epithelial cell injury?
AB  - Helicobacter pylori infection results in peptic ulceration and chronic gastritis
      through mechanisms which are not fully elucidated. Live H. pylori activate the
      pro-inflammatory transcription factor NF-kappaB in gastric epithelial cells.
      Patients may have peptic ulcer disease in the absence of H. pylori infection;
      therefore other factors contribute to the inflammatory process. Maximal acid
      output in patients with H. pylori infection and duodenal ulceration is
      significantly increased indicating a role for acid in the pathogenesis of mucosal
      ulceration. The effect of low pH on NF-kappaB activation in gastric epithelial
      cells has not been studied. Human gastric epithelial cells (AGS) were exposed to
      a range of pH changes in the presence or absence of H. pylori. NF-kappaB DNA
      binding and cytosolic IkappaB-alpha were measured using electrophoretic mobility
      shift assay and Western blotting. NF-kappaB DNA-binding in gastric epithelial
      cells dramatically increased when the pH of the culture medium decreased.
      Increases in NF-kappaB nuclear binding were paralleled by decreasing amounts of
      cytosolic IkappaB-alpha. These findings were similar but less potent than those
      observed when cells were exposed to H. pylori. Low pH resulted in enhancement of
      H. pylori-induced NF-kappaB nuclear binding. DNA binding of NF-kappaB activation
      secondary to low pH was attenuated by PD98059 but not by SB203580. Similar to H.
      pylori, low pH potently and independently augments NF-kappaB nuclear binding in
      AGS cells and such activation appears to be mediated through MEK1-dependant
      signaling pathways.

PMID- 16088960
TI  - During male pronuclei formation chromatin remodeling is uncoupled from nucleus
      decondensation.
AB  - Male pronucleus formation involves sperm nucleus decondensation and sperm
      chromatin remodeling. In sea urchins, male pronucleus decondensation was shown to
      be modulated by protein kinase C and a cdc2-like kinase sensitive to olomoucine
      in vitro assays. It was further demonstrated that olomoucine blocks SpH2B and
      SpH1 phosphorylation. These phosphorylations were postulated to participate in
      the initial steps of male chromatin remodeling during male pronucleus formation.
      At final steps of male chromatin remodeling, all sperm histones (SpH) disappear
      from male chromatin and are subsequently degraded by a cysteine protease. As a
      result of this remodeling, the SpH are replaced by maternal histone variants
      (CS). To define if sperm nucleus decondensation is coupled with sperm chromatin
      remodeling, we have followed the loss of SpH in zygotes treated with olomoucine.
      SpH degradation was followed with anti-SpH antibodies that had no cross
      reactivity with CS histone variants. We found that olomoucine blocks SpH1 and
      SpH2B phosphorylation and inhibits male pronucleus decondensation in vivo.
      Interestingly, the normal schedule of SpH degradation remains unaltered in the
      presence of olomoucine. Taken together these results, it was concluded that male
      nucleus decondensation is uncoupled from the degradation of SpH associated to
      male chromatin remodeling. From these results, it also emerges that the
      phosphorylation of SpH2B and SpH1 is not required for the degradation of the SpH
      that is concurrent to male chromatin remodeling.

PMID- 16088961
TI  - Cyclic AMP-dependent modification of gonad-selective TAF(II)105 in a human
      ovarian granulosa cell line.
AB  - In response to gonadotropins, the elevated level of intracellular-cyclic AMP
      (cAMP) in ovarian granulosa cells triggers an ordered activation of multiple
      ovarian genes, which in turn promotes various ovarian functions including
      folliculogenesis and steroidogenesis. Identification and characterization of
      transcription factors that control ovarian gene expression are pivotal to the
      understanding of the molecular basis of the tissue-specific gene regulation
      programs. The recent discovery of the mouse TATA binding protein (TBP)-associated
      factor 105 (TAF(II)105) as a gonad-selective transcriptional co-activator
      strongly suggests that general transcription factors such as TFIID may play a key
      role in regulating tissue-specific gene expression. Here we show that the human
      TAF(II)105 protein is preferentially expressed in ovarian granulosa cells. We
      also identified a novel TAF(II)105 mRNA isoform that results from alternative
      exon inclusion and is predicted to encode a dominant negative mutant of
      TAF(II)105. Following stimulation by the adenylyl cyclase activator forskolin,
      TAF(II)105 in granulosa cells undergoes rapid and transient phosphorylation that
      is dependent upon protein kinase A (PKA). Thus, our work suggests that pre-mRNA
      processing and post-translational modification represent two important regulatory
      steps for the gonad-specific functions of human TAF(II)105.

PMID- 16088962
TI  - First analysis of patient demographics, technical reproducibility, cosmesis, and
      early toxicity: results of the American Society of Breast Surgeons MammoSite
      breast brachytherapy trial.
AB  - BACKGROUND: Eighty-seven institutions participated in a Registry Trial that was
      designed to collect data on the clinical use of the MammoSite breast
      brachytherapy catheter for delivering breast irradiation. Patient demographics,
      technical reproducibility, cosmesis, and early toxicity were evaluated. METHODS:
      From May 4, 2002 through July 30, 2004, 1419 patients with Stage 0, I, or II
      breast carcinoma who were undergoing breast-conserving therapy were enrolled on
      the trial. The device was placed in 1403 of these patients. The 1237 patients
      (87% of enrolled patients) who received accelerated partial breast irradiation
      (APBI) (34 grays prescribed to 1.0 cm in 10 fractions; 95% of patients who
      received APBI) constituted the study population; 86% of those patients (1068) had
      Stages I-II breast carcinoma (median tumor size, 10 mm), and 14% of those
      patients (169) had Stage 0 breast carcinoma. Ninety-one percent of the patients
      with invasive carcinoma (977 of 1068 patients) had negative lymph node status,
      and 99% of all patients had negative margins. The median patient age was 65
      years. Systemic chemotherapy alone was administered to 79 patients with invasive
      carcinoma (7%), hormone therapy was administered to 501 patients (45%), and both
      were administered to 39 patients (4%). The median follow-up was 5 months.
      RESULTS: Five hundred fifty-four catheters (45%) were placed with an open cavity
      at the time of lumpectomy, and 683 catheters (55%) were placed with a closed
      cavity after lumpectomy. Skin spacing ranged from 2 mm to 75 mm (median, 10 mm).
      In 89% of patients, there was a minimum balloon-to-skin distance of 7 mm (2% of
      patients had distances < 5 mm). In terms of cosmetic assessment, 95% of patients
      (1030 of 1084 patients) who had a cosmetic assessment had a good/excellent result
      (last follow-up visit). Cosmetic results at 12 months were good/excellent in 92%
      of 248 evaluable patients. The median skin spacing (> or = 7 mm vs. < 7 mm) was
      associated significantly with a good/excellent cosmetic result (96.1% vs. 86.8%;
      P = 0.0001) overall and at 6 months (P = 0.006). Increasing skin spacing was
      associated with a good/excellent cosmetic result as a continuous variable (P <
      0.0001). In total, 92 of 1140 evaluable patients (8.1%) developed an infection in
      the breast, which was device-related in 5.3% of patients (60 of 1140 patients).
      Good/excellent cosmetic results were noted in 86% of these patients (last follow
      up visit). Fifteen of 442 evaluable patients (3.4%) developed a radiation recall
      reaction. Good/excellent cosmetic results were noted in 93% of these patients at
      their last follow-up visit. One local recurrence (0.1%) was reported (new primary
      carcinoma). CONCLUSIONS: Clinical evaluation of the ability of the MammoSite
      breast brachytherapy catheter to deliver APBI demonstrated acceptable technical
      reproducibility between multiple institutions and use in appropriate groups of
      patients. Cosmetic results at 12 months (92% good/excellent) were comparable to
      those reported with whole-breast RT. Early toxicity rates (infections, radiation
      recall) appeared to be acceptable.

PMID- 16088963
TI  - Anorexia/cachexia-related quality of life for children with cancer.
AB  - BACKGROUND: Anorexia is a common symptom in patients with cancer, which can lead
      to poor tolerance of treatment and can contribute to cachexia in extreme cases.
      Children with advanced-stage cancer are especially vulnerable to malnutrition
      resulting from anorexia and cachexia. Currently, there are no instruments that
      measure common concerns specifically associated with anorexia and cachexia in
      children with cancer. The purpose of the current article was to test the
      psychometric properties of a newly developed pediatric Functional Assessment of
      Anorexia and Cachexia Therapy (peds-FAACT) for children with cancer. METHODS:
      Ninety-six patients (ages 7-17 yrs) receiving cancer treatment and their parents
      were asked to complete the 12-item peds-FAACT. The authors implemented both
      classical test theory and item response theory to evaluate the agreement between
      parents and patients, internal consistency and unidimensionality of the scale,
      and stability of items across subgroups. RESULTS: As a result, a patient-reported
      six-item scale was recommended as the core measure for all pediatric patients
      with cancer and four additional peripheral items were recommended for adolescent
      patients. CONCLUSIONS: The peds-FAACT demonstrated good psychometric properties,
      differentiated patients with different functional performance status, and was
      determined to be a useful tool for future clinical trials.

PMID- 16088964
TI  - Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant
      glioma.
AB  - BACKGROUND: The authors determined the maximum tolerated dose (MTD) and dose
      limiting toxicity (DLT) of irinotecan (CPT-11), a topoisomerase I inhibitor, when
      administered with temozolomide among patients with recurrent malignant glioma
      (MG). METHODS: Patients with MG at any recurrence received temozolomide (TMZ) at
      a dose of 200 mg/m(2)/day on Days 1-5 plus CPT-11 administered as a 90-minute
      intravenous infusion during Weeks 1, 2, 4, and 5 of each 6-week cycle. Patients
      were stratified based on concurrent administration of CYP3A4-inducing
      anticonvulsants (enzyme-inducing antiepileptic drugs [EIAEDs]). The CPT-11 dose
      was escalated in successive cohorts of patients independently for each stratum.
      RESULTS: CPT-11, at doses ranging from 40 mg/m(2) to 375 mg/m(2), was
      administered with TMZ to 107 patients. Ninety-one patients (85%) had recurrent
      glioblastoma multiforme (GBM) and 16 (15%) had recurrent anaplastic glioma. Sixty
      eight patients (64%) were given EIAEDs. The MTD of CPT-11 for patients
      concurrently receiving and not receiving EIAEDs was 325 mg/m(2) and 125 mg/m(2),
      respectively. The DLTs were hematologic, gastrointestinal, and hepatic. Fifteen
      patients (14%) achieved either a radiographic complete (n = 5) or partial (n =
      10) response across a wide range of CPT-11 dose levels. Patients with recurrent
      GBM who achieved radiographic response had a median time to disease progression
      of 54.9 weeks. CONCLUSIONS: The current study built on preclinical observations
      designed to increase the clinical activity of topoisomerase I inhibitors. CPT-11,
      administered at full dose levels, was well tolerated in combination with TMZ.
      Furthermore, durable responses were observed in this recurrent population.
      Ongoing Phase II studies will evaluate the efficacy of this regimen and its
      application to other malignancies.

PMID- 16088965
TI  - New aromatase inhibitors as second-line endocrine therapy in postmenopausal
      patients with metastatic breast carcinoma: a pooled analysis of the randomized
      trials.
AB  - BACKGROUND: New aromatase inhibitors (AI) (second-generation: formestane and
      fadrozole; third-generation: letrozole, anastrozole, vorozole, and exemestane)
      have been tested in several controlled clinical trials after tamoxifen failure in
      metastatic breast carcinoma (MBC). They have resulted in better survival compared
      with megestrol acetate (MEG) in a number of studies. The authors performed a
      pooled analysis including all the Phase III trials published between 1996 and
      2004 evaluating the AIs approved or not by the Food and Drug Administration (FDA)
      and the European Agency for the Evaluation of Medical Products (EMEA) as second
      line endocrine therapy (ET) for patients with MBC. METHODS: The overall response
      rate (ORR) and time to disease progression (TTP) were considered the primary end
      points, whereas toxicity was regarded as a secondary objective. Relative risk,
      95% confidence interval, and heterogeneity were derived using 2 methods. RESULTS:
      No significant differences in ORR and TTP were noted in the entire group of 9
      trials comparing AI with MEG (3908 patients) and in the 6 trials comparing
      nonsteroidal AI and MEG (2415 patients). AI yielded significantly more hot
      flashes than MEG (P = 0.004) but caused significantly less toxicity than MEG in
      weight gain (P = 0.001), dyspnea (P = 0.008), and peripheral edema (P = 0.03).
      Significant heterogeneity for nausea, weight gain, dyspnea, and peripheral edema
      was registered. When steroidal AIs were excluded from the toxicity analysis,
      nausea maintained its strongly significant heterogeneity (P = 0.0002), whereas
      weight gain, dyspnea, and peripheral edema lost their significance. CONCLUSIONS:
      This pooled analysis suggested that AIs in second-line ET for patients with MBC
      do not seem to add any significant benefit to MEG in terms of ORR and TTP. With
      regard to toxicity, the findings in the current study showed that weight gain,
      dyspnea, and peripheral edema are more frequent with the use of MEG, whereas hot
      flashes were more represented using AI.

PMID- 16088966
TI  - The prognostic impact of histology and 1p/19q status in anaplastic
      oligodendroglial tumors.
AB  - BACKGROUND: It has been reported previously that the combined loss of chromosomal
      arms 1p and 19q is a significant predictor of outcome for patients with
      anaplastic oligodendroglial (AO) tumors and that such chromosomal loss correlates
      with classic histology in AO. The authors sought to determine whether histology
      was an equivalent or superior predictor of outcome compared with 1p/19q status in
      131 patients with AO tumors. METHODS: The status of 1p and 19q was determined
      using real-time, quantitative polymerase chain reaction analysis and/or
      fluorescence in situ hybridization. Clinical features (response to adjuvant
      therapy and tumor location) and molecular genetic abnormalities (9p and 10q
      deletions, overexpression of p53 and epidermal growth factor receptor) were
      determined on available specimens. Histologic assessments for classic
      oligodendroglial features were performed by five neuropathologists. RESULTS:
      Classic histology was associated closely with 1p/19q loss, as reported
      previously. Patients who had tumors that were considered classic by at least four
      of the five neuropathologists showed significantly increased progression-free and
      overall survival compared with the patients who had less classic tumors. The
      authors also tested the correlation between 1p/19q status and outcome in subsets
      of patients stratified according to classic tumor features. The association of
      1p/19q status with survival was related closely to the presence of classic
      histology. Loss of 1p/19q was predictive of improved outcome only among patients
      who had tumors with classic histologic features. CONCLUSIONS: The current results
      suggested that, in addition to 1p/19q status, histologic features contribute
      information to the prediction of outcome in patients with AO. Loss of 1p and 19q
      appeared to be a prognostic marker only in the subset of patients who had AO
      tumors with classic histologic features.

PMID- 16088967
TI  - Electrospray ionization suppression, a physical or a chemical phenomenon?
AB  - Mass spectrometry is a powerful qualitative and quantitative analytical technique
      that has been introduced in many bioanalytical and research laboratories in the
      last 10 years. The combination of HPLC with tandem MS yields a particularly
      powerful tool and it is now the method of choice for the analysis drugs,
      metabolites, biomarkers and proteins. However, HPLC-MS methods are not completely
      without problems that can compromise the quality of the results. An important
      phenomenon that can affect the quantitative performance of a mass detector is ion
      suppression. In this study, we measured the influence of the observed current (I)
      vs signal intensity and the variation of the observed current (I) when analyzing
      biological samples. Our experiment suggests that, despite the fact that it is
      possible for other chemicals to compete for protons in the droplets, the increase
      in the observed current (I) during the signal suppression is important and
      indicates that the conductivity of the liquid increases significantly. The salts
      and the charged species influence the conductivity and the surface tension of the
      droplets and modify the equilibrium between the two main forces involved during
      the electrospray process, resulting in an erratic spray behavior.

PMID- 16088968
TI  - Determination of drug absorption rate in time-variant disposition by direct
      deconvolution using beta clearance correction and end-constrained non-parametric
      regression.
AB  - A novel numerical deconvolution method is presented that enables the estimation
      of drug absorption rates under time-variant disposition conditions. The method
      involves two components. (1) A disposition decomposition-recomposition (DDR)
      enabling exact changes in the unit impulse response (UIR) to be constructed based
      on centrally based clearance changes iteratively determined. (2) A non
      parametric, end-constrained cubic spline (ECS) input response function estimated
      by cross-validation. The proposed DDR-ECS method compensates for disposition
      changes between the test and the reference administrations by using a "beta"
      clearance correction based on DDR analysis. The representation of the input
      response by the ECS method takes into consideration the complex absorption
      process and also ensures physiologically realistic approximations of the
      response. The stability of the new method to noisy data was evaluated by
      comprehensive simulations that considered different UIRs, various input
      functions, clearance changes and a novel scaling of the input function that
      includes the "flip-flop" absorption phenomena. The simulated input response was
      also analysed by two other methods and all three methods were compared for their
      relative performances. The DDR-ECS method provides better estimation of the input
      profile under significant clearance changes but tends to overestimate the input
      when there were only small changes in the clearance.

PMID- 16088969
TI  - Prevention of nutritionally induced diabetes by rosiglitazone in the gerbil
      Psammomys obesus.
AB  - BACKGROUND: Psammomys obesus is a desert gerbil developing hyperglycaemia,
      hyperinsulinaemia and insulin resistance when placed for 2 weeks on a high-energy
      (HE) diet. The mechanism underlying the antidiabetic effect of rosiglitazone (RG)
      treatment (20 mg/kg per day for 2 weeks) was studied. METHODS: The
      antidiabetogenic effect of RG treatment on serum insulin and metabolic parameters
      in serum and target tissues of insulin action was investigated in vivo and
      compared with the pancreatic beta cell protective effects of RG. RESULTS: Almost
      all RG-treated animals remained normoglycaemic compared to controls, but, at the
      same time, they were hyperinsulinaemic. RG had no effect on serum free fatty acid
      and serum and muscle triglyceride concentrations and did not appreciably affect
      body weight and fat depots. RG prevented a HE diet-induced reduction of GLUT 4
      glucose transporter content in epididymal adipose tissue, but not in
      gastrocnemius muscle. The normoglycaemic effect was not associated with a
      suppression of liver PEPCK activity. Muscle PKCepsilon expression, known to be
      elevated in diabetic Psammomys and to inhibit insulin signalling, was only
      marginally decreased. However, RG treatment prevented the marked decrease in
      insulin immunostaining as well as the vacuolization of the beta cells and
      accelerated beta cell proliferation. CONCLUSIONS: These data indicate that the
      skeletal muscle is not the primary target of RG action, whereas the preservation
      of the insulin secretory capacity and the prevention of degenerative beta cell
      vacuolization in spite of persisting insulin resistance appear to be the basis
      for the anti-hyperglycaemic effect of RG in Psammomys.

PMID- 16088970
TI  - Elevated serum urate concentration independently predicts poor outcome following
      stroke in patients with diabetes.
AB  - BACKGROUND: Type 2 diabetes is a risk factor for stroke and confers increased
      risk of poor outcome and further vascular events following stroke. Hyperuricaemia
      occurs commonly in patients with type 2 diabetes, but its significance as a
      predictor of outcome following stroke is uncertain. We sought to investigate the
      prognostic significance of elevated serum urate concentration in diabetic
      subjects following stroke. METHODS: We studied a cohort of type 2 diabetes
      patients presenting to our unit with computed tomography-confirmed acute stroke.
      Fasting blood samples were drawn within 24 h of admission for urate concentration
      and standard battery of biochemistry and hematological tests. Information on age,
      stroke type, prior hypertension, smoking status, resolution time of symptoms and
      National Institutes of Health Stroke Score was collated. The main outcome event
      was time to myocardial infarction, recurrent stroke or vascular death, as defined
      in the CAPRIE trial. Stepwise proportional hazards regression was used to
      estimate the effect of the above variables on event-free survival following
      stroke. RESULTS: One hundred and forty patients were studied. Median follow-up
      duration was 974 days (IQR 163 to 1830 days). Sixty-four patients suffered an
      outcome event. Urate levels of greater than 0.42 mmol/L (p < 0.001) and an
      increasing NIHSS score (p < 0.001) independently predicted increased likelihood
      of suffering an event. CONCLUSION: Elevated urate concentration is significantly
      and independently associated with increased risk of future vascular events in
      diabetic stroke patients. Further studies to elucidate the mechanism of this
      observation are required.

PMID- 16088971
TI  - Computational methods in coupled electron-ion Monte Carlo simulations.
AB  - In the last few years, we have been developing a Monte Carlo simulation method to
      cope with systems of many electrons and ions in the Born-Oppenheimer
      approximation: the coupled electron-ion Monte Carlo method (CEIMC). Electronic
      properties in CEIMC are computed by quantum Monte Carlo rather than by density
      functional theory (DFT) based techniques. CEIMC can, in principle, overcome some
      of the limitations of the present DFT-based ab initio dynamical methods. The new
      method has recently been applied to high-pressure metallic hydrogen. Herein, we
      present a new sampling algorithm that we have developed in the framework of the
      reptation quantum Monte Carlo method chosen to sample the electronic degrees of
      freedom, thereby improving its efficiency. Moreover, we show herein that, at
      least for the case of metallic hydrogen, variational estimates of the electronic
      energies lead to an accurate sampling of the proton degrees of freedom.

PMID- 16088972
TI  - Phase stability and broken-symmetry transition of elemental lithium up to 140
      GPa.

PMID- 16088973
TI  - Reversible hydride generation and release from the ligand of
      [Ru(pbn)(bpy)2](PF6)2 driven by a pbn-localized redox reaction.

PMID- 16088974
TI  - Stereospecific and stereoselective preparation of 2-(1-hydroxyalkyl)-1
      alkylcyclopropanols from alpha,beta-epoxy ketones and bis(iodozincio)methane.

PMID- 16088976
TI  - Structural analysis of lignin by resonance Raman spectroscopy.
AB  - Resonance Raman (RR) spectroscopy, combined with Kerr gated fluorescence
      rejection in the time domain, has recently elucidated lignin structure with
      unique sensitivity and selectivity. This promises structural studies of
      fluorescent natural macromolecules, such as lignin, which were previously not
      possible. Such studies rely on an improved understanding of the RR spectral
      behavior of lignin, which is today scarcely understood. We explain for the first
      time this behavior by a semi-empirical theory, and observe its pertinent features
      for lignin in vascular plants. We have used well-defined oxidative treatments as
      means of probing lignin structural elements, and show that RR sensitivity and
      selectivity depend crucially on excitation wavelength. Through the theory we
      relate these results to basic structural aspects of lignin. Spectra obtained by
      blue light laser excitation (400 nm) are dominated by low redox potential
      syringyl lignin groups, whereas lower photon energy (500 nm) decreases the
      selectivity markedly. RR bands depend on molecular structure but also on
      molecular environment. Thus charge transfer donor-acceptor interactions within
      lignin reduce the intensity of bands associated with electron rich moieties. New
      possibilities for basic and selective structural information on fluorescent
      natural materials, such as lignin, have thus appeared.

PMID- 16088978
TI  - AKT activation predicts outcome in breast cancer patients treated with tamoxifen.
AB  - Oestrogen receptor (ERalpha) expression is a strong predictor of response to
      endocrine therapy. The PI3K/AKT/mTOR signal transduction pathway has been
      implicated in endocrine resistance in vitro. The present study was carried out to
      test the hypothesis that AKT activation mediates tamoxifen resistance in clinical
      breast cancer. Immunohistochemistry (IHC) using AKT1-3, pan-AKT, pAKT (Thr-308),
      pAKT (Ser-473), pER (Ser-167), and pHER2 antibodies was performed on 402 ERalpha
      positive breast carcinomas from patients treated with tamoxifen. High pAKT (Ser
      473) activity (p = 0.0406) and low AKT2 expression (p = 0.0115) alone, or in
      combination [high pAKT (Ser-473)/low AKT2; 'high-risk' patient group] (p =
      0.0014), predicted decreased overall survival in tamoxifen-treated patients with
      ERalpha-positive breast cancers. There was no significant association between
      tumour levels of AKT expression or activity and disease-free survival (DFS);
      however, the 'high-risk' patient group was significantly more likely to relapse
      (p = 0.0491). During tamoxifen treatment, neither AKT2 nor pAKT predicted DFS.
      Finally, activation of AKT, via phosphorylation, was linked to activation of both
      HER2 and ERalpha in this patient cohort. The data presented here show that the
      PI3K/AKT/mTOR pathway is associated with relapse and death in ERalpha-positive
      breast cancer patients treated with tamoxifen, supporting in vitro evidence that
      AKT mediates tamoxifen resistance. Patients with a 'high-risk' expression profile
      were at increased risk of death (hazard ratio 3.22, p = 0.002) relative to 'low
      risk' patients, highlighting the potential that tumour profiling, with multiple
      IHC markers predictive of therapeutic response, may improve patient selection for
      endocrine therapies, eg tamoxifen or aromatase inhibitor-based treatments.

PMID- 16088979
TI  - The concept of the 'percent wasted patients' in preventive health strategies.
AB  - PURPOSE: To better communicate the impact of poor persistence when preventive
      therapies are initiated, we propose a new measure that is intuitively
      understandable for clinicians. This measure is the percent wasted patients (PWP).
      METHODS: The PWP is the percentage of patients, out of the new users of a given
      preventive treatment, who have discontinued therapy before the time point at
      which clinical benefits become apparent on the cumulative incidence curves in
      randomized controlled trials (RCTs) comparing active treatment to placebo. To
      calculate the PWP, the RCTs that demonstrated the efficacy of the therapy under
      study must be identified from a MEDLINE search. The point at which the cumulative
      incidence curves for the main outcome in the experimental and placebo group start
      diverging is identified and is called the point of visual divergence (PVD). Then,
      using pharmaceutical claims databases, the percent persistence at the PVD in new
      users of the therapy is determined. The PWP is then calculated as 100%
      persistence at PVD. RESULTS: For primary prevention with statins, in the province
      of Quebec, the PWP is 44%. Of 100 patients starting statins for the primary
      prevention of coronary events, 44 will represent a waste in health resources
      because they will have discontinued therapy before any clinical benefit can be
      expected. CONCLUSIONS: The PWP is a simple measure that can be used by clinicians
      to select the therapies that need the most reinforcement concerning the
      importance of persistence.

PMID- 16088980
TI  - A ranked presentation of the MHRA/CSM (Medicines & Health Care Regulatory
      Agency/Committee on Safety of Medicines) Drug Analysis Print (DAP) data on
      practolol.
AB  - PURPOSE: To display a ranked presentation of the data given in the Drug Analysis
      Prints (DAPs) provided by the MHRA/CSM so that the monitoring clinician may be
      readily alerted to the most important findings. The practolol DAP is taken as an
      example of the presentation. METHOD: The data for the ranked system organ
      classes, the ranked deaths and the ranked reaction reports within each system
      organ class are considered separately. RESULTS: It has been found that there are
      advantages in considering the system-organ classes, the deaths and the reports of
      the individual reactions separately and then, within these groupings, providing
      the mathematically ranked data. The results for practolol, withdrawn due to the
      associated oculomucocutaneous syndrome, are given as a single worked example.
      CONCLUSIONS: Presentations of the ranked data arising from spontaneous adverse
      drug reactions reporting may have useful advantages.

PMID- 16088981
TI  - Revealing alcohol abuse: to ask or to test?

PMID- 16088982
TI  - Original series of screening, evaluation, and care of adolescent substance abuse.

PMID- 16088983
TI  - World Health Organization/International Society for Biomedical Research on
      Alcoholism study on state and trait markers of alcohol use and dependence: back
      to the future.

PMID- 16088984
TI  - Alcoholic liver disease: from pathophysiology to therapy.

PMID- 16088985
TI  - Advances in alcoholism research in Germany.

PMID- 16088986
TI  - Health economics of addiction.

PMID- 16088987
TI  - Neuroactive steroids and ethanol.

PMID- 16088988
TI  - Control of basic fibroblast growth factor release from fibrin gel with heparin
      and concentrations of fibrinogen and thrombin.
AB  - Basic fibroblast growth factor (bFGF) has been known to stimulate the
      regeneration of a number of tissues including cartilage, nerve, skin, liver, and
      blood vessel. Delivery of bFGF for a long period in a controlled manner would
      enhance stimulative effects. The purpose of the present study is to test the
      hypothesis that the kinetics of bFGF release from fibrin gels could be controlled
      with heparin and concentrations of fibrinogen and thrombin. The kinetics of bFGF
      release from fibrin gels with various concentrations of fibrinogen, thrombin, and
      heparin was determined. The bioactivity of bFGF released from fibrin gels was
      assessed using dermal fibroblast cell culture. To examine the therapeutic
      potential of the bFGF delivery system, bFGF-loaded fibrin gels were injected into
      mouse ischemic limbs. The addition of heparin to fibrin gels decreased the bFGF
      release rate. As the thrombin content in fibrin gels increased, the bFGF release
      rate significantly decreased. Similarly, increased concentration of fibrinogen in
      fibrin gels decreased the bFGF release rate. Basic FGF released from fibrin gels
      exhibited significantly higher extents of fibroblast growth than bFGF added in a
      free form daily into the culture medium, suggesting that the fibrin gels may
      stabilize the bFGF bioactivity. Immunohistological analysis of mouse ischemic
      limbs indicated that the microvessel density was much higher in the ischemic
      limbs treated with injection of bFGF-loaded fibrin gels than in the ischemic
      limbs with no treatment. This study showed that the rate of bFGF release from
      fibrin gels can be controlled and that the bFGF delivery system has therapeutic
      potentials for angiogenesis.

PMID- 16088989
TI  - Weight adjusted spinal anaesthesia for Caesarean section.

PMID- 16088990
TI  - [Comments on a critical consideration of a modern construct--subjective life
      quality].

PMID- 16088991
TI  - Weight adjusted spinal anaesthesia for Caesarean section.

PMID- 16088992
TI  - Signal transduction in alcohol-related diseases.

PMID- 16088994
TI  - Mechanisms in alcohol-associated carcinogenesis.

PMID- 16088993
TI  - Recent advances in alcohol-induced adduct formation.

PMID- 16088995
TI  - Recent developments in the genetics of alcohol-related phenotypes.

PMID- 16088997
TI  - Health risks of chronic moderate and heavy alcohol consumption: how much is too
      much?
AB  - This article presents the proceedings of a symposium held at the meeting of the
      International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim,
      Germany, in October 2004. Most of what we know about the deleterious effects of
      alcohol in vivo has been gleaned from studies in sober alcoholics recruited from
      substance abuse treatment programs. Little is known about effects of chronic
      drinking in the moderate or heavy range encountered in a much larger fraction of
      modern society. Extrapolation of information on the adverse effects of chronic
      drinking on organ function from clinical samples to social drinkers in the
      general population has to be met with great skepticism, as it may lead to wrong
      conclusions about the chronic effects of alcohol in social drinkers. Several
      recent studies suggest that moderate alcohol consumption has certain beneficial
      health effects, whereas heavy social alcohol consumption has recently been
      associated with organ abnormalities and cognitive deficits. These social drinking
      effects have attracted great public interest; reports of benefits of moderate
      drinking have also inspired inappropriate publications by the media, including
      misleading advertisements by the alcohol producing and distributing industry.
      Although adverse effects of moderate to heavy drinking on heart, liver, and
      cancer development have attracted attention by clinicians and researchers for
      some time, its compromising effects on brain and cognition have only recently
      been studied. This symposium brought together researchers from different
      disciplines, who reviewed and presented new data on consequences of social
      drinking in the areas of clinical neuropsychology and behavior (Drs. Nixon and
      Meyerhoff), neurophysiology (Dr. Nixon, Ms. De Bruin), neuroimaging (Ms. de
      Bruin, Dr. Meyerhoff), hepatic disease (Dr. Bode), and cancer (Dr. Seitz). The
      symposium aimed to clarify both the potential health benefits of moderate alcohol
      consumption and risks of moderate and heavy drinking on proper organ function and
      to provide insights and new data to practicing physicians and public health
      authorities for education on problem drinking.

PMID- 16088996
TI  - Factors mediating alcohol craving and relapse: stress, compulsivity, and
      genetics.

PMID- 16088998
TI  - From alcohol toxicity to treatment.
AB  - This article presents the proceedings of a symposium held at the meeting of the
      International Society for Biomedical Research on Alcoholism in Mannheim, Germany,
      in October 2004. This symposium was dedicated to Charles S. Lieber in recognition
      of his contribution in alcohol research over the last 50 years. It was divided
      into two parts, namely effects of alcohol on the gastrointestinal tract and
      effects of alcohol on the liver. Major emphasis was given to recent discoveries
      elucidating mechanisms of alcohol-associated carcinogenesis. M. Salaspuro
      (Finland) discussed the role of acetaldehyde in the saliva and in the large
      intestine with respect to its role in the pathogenesis of alcohol-associated
      cancer, and H. K. Seitz (Germany) presented new data identifying individuals
      homozygous for the ADH1C&1 allele as high on risk for alcohol-associated upper
      aerodigestive tract cancer. M. Savolainen (Finland) discussed the role
      phosphatidylethanol as a bioactive lipid that can mediate beneficial and harmful
      effects of alcohol drinking. In the second part of the symposium, alcoholic liver
      disease was discussed. P. Haber (Australia) presented new data on hepatic
      transcriptome in alcoholic liver disease with the identification of new genes
      possibly involved in alcohol-initiated fibrogenesis of the liver, and H. Moshage
      (The Netherlands) described survival mechanisms of the cholestatic hepatocytes
      with implications for therapy in cholestatic liver disease. The role of the
      hepatic microsomal ethanol oxidizing system in the metabolism of alcohol in
      alcoholic liver disease was summarized by R. Teschke (Germany). H. Ishii (Japan)
      discussed the current status and treatment of alcoholic hepatitis in Japan.
      Finally, in a state-of-the-art lecture, Charles S. Lieber (USA) discussed the
      development of the understanding of the pathophysiology of alcoholic liver
      disease in the last 50 years. He emphasized the role of pathophysiology as an
      important prerequisite for better treatment strategies.

PMID- 16088999
TI  - Suppression of the HPA axis stress-response: implications for relapse.
AB  - This article presents the proceedings of a symposium held at the meeting of the
      International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim,
      Germany, in October 2004. This symposium explored the potential role of
      hypothalamic-pituitary-adrenal (HPA) axis dysregulation upon relapse. HPA axis
      stimulation induces the release of the glucocorticoid cortisol, a compound with
      profound effects upon behavior and emotion. Altered stress-responses of the HPA
      axis in abstinent alcohol-dependent subjects, therefore, may influence their
      affective and behavioral regulation, thus impacting their potential for relapse.
      Bryon Adinoff began the symposium with a review of HPA axis dysfunction in
      alcohol-dependent subjects, including recent studies from his lab demonstrating
      an attenuated glucocorticoid response to both endogenous and exogenous
      stimulation in one-month abstinent men. Klaus Junghanns presented his work
      demonstrating that a blunted ACTH or cortisol response to subjective stressors
      (social stressor or alcohol exposure) is predictive of a return to early
      drinking. The final two presenters examined the interaction between naltrexone
      and HPA responsiveness in alcohol-dependent or at-risk subjects, as naltrexone
      induces an increase in ACTH and cortisol. Falk Kiefer discussed the relationship
      between basal HPA axis responsivity and clinical outcome following treatment with
      naltrexone or acamprosate. Plasma ACTH significantly decreased over the course of
      the study in the placebo group, but not the medication groups [corrected] Lower
      basal concentrations of ACTH and cortisol were associated with quicker relapse in
      the placebo group only. Suchitra Krishnan-Sarin described her preliminary work,
      in which family-history positive (FH+) and family history negative (FH-) subjects
      were administered naltrexone, followed by an assessment of alcohol-induced
      craving. The cortisol response to alcohol was significantly and inversely related
      to craving in the FH+, but not the FH-, subjects. Alterations in HPA axis
      responsivity may therefore have a negative impact upon clinical outcome in
      alcohol-dependent subjects, and disinhibition of the axis with medication may
      have therapeutic potential.

PMID- 16089001
TI  - Niger and its implications for health security.

PMID- 16089000
TI  - Remembering Hiroshima.

PMID- 16089002
TI  - Overcoming health inequalities in the USA.

PMID- 16089003
TI  - The day the bomb fell.

PMID- 16089004
TI  - Hiroshima: how much have we learned?

PMID- 16089005
TI  - Bibliography. Current world literature. Insect allergy.

PMID- 16089006
TI  - Wellcome funding.

PMID- 16089007
TI  - Strength in numbers.

PMID- 16089008
TI  - Strong bonds.

PMID- 16089009
TI  - Software solutions.

PMID- 16089010
TI  - A new role for psychologists--hospital ethics committees.
AB  - Over the past decade psychology has begun to appreciate that it represents more
      than "merely mental health care" and has become increasingly involved in the
      generic health care arena. The participation of psychologists in Hospital Ethics
      Committees (HECs) is presented as a professional activity for which psychologists
      are particularly well suited. The clinical mission of HECs, the historical
      importance of ethical considerations to psychology, and the field's specific
      training and psycho-social expertise suggest valuable contributions that
      psychologists can make in this particular area. Further, as psychology actively
      increases its participation in HECs, other professional disciplines outside of
      the mental health field will systematically have the opportunity to become more
      familiar with psychology and its clinical and research expertise.

PMID- 16089011
TI  - A hematopoietic stromal lesion associated with fractionated radiotherapy (FxRT):
      time- and dose-effects.
AB  - Earlier, we reported that the local exposure of femoral bone marrow to a
      clinically-relevant course of fractionated radiotherapy [FxRT; 2.0 Gy (q24h x 5) 
      -> 74 Gy] resulted in the delayed appearance of a stromal lesion which temporally
      appeared after exposures to a threshold dose of 20 Gy FxRT. To further define
      this threshold dose, the temporal recovery of blood-forming elements
      ("cobblestone area" forming colonies; CAFC(7-28d)) and the microenvironmental
      stroma (long-term bone marrow cultures; LTBMC) of the marrow was examined over a
      17-week period following 10 and 30 Gy FxRT. After a subthreshold dose of 10 Gy,
      each of the 4 CAFC subpopulations were significantly dampened, with recovery
      initiated within a 6-week interval of 10 Gy of FxRT. Above the threshold dose (30
      Gy FxRT), the CAFC subpopulations were again reduced to a level similar to that
      observed with 10 Gy FxRT. However, after exposures to 30 Gy FxRT, CAFC recovery
      was significantly well beyond the 6-week interval observed with a 10 Gy Dose of
      FxRT. Similarly, cell production in LTBMC prepared from marrow exposed to either
      10 or 30 Gy FxRT was significantly dampened for at least 3 weeks following the
      FxRT. Moreover, while cell production in LTBMC derived from marrow exposed to 10
      Gy was eventually restored to normal, the dampened cell production observed in
      LTBMC prepared after 30 Gy FxRT persisted for a period in excess of 17 weeks.
      Collectively, these observations provide additional support to our earlier
      observation suggesting that FxRT generates two forms of dose-dependent damage in
      the marrow: the first an early lesion arising in the blood-forming CAFC
      subpopulations; the second form, a delayed lesion that involves the persistent
      expression of a dysfunctional microenvironmental phenotype, appearing to disrupt
      the normal regulation of hematopoietic stem cell (HSC) proliferation and
      differentiation of the HSC during the recovery process.

PMID- 16089012
TI  - Chemical biology: innovative solutions for diverse challenges.

PMID- 16089013
TI  - [Analysis of antiretroviral-therapy-derived costs in a group 2 hospital during
      2002 and 2003].

PMID- 16089014
TI  - [Peripheral blood smear utility in meningococcal sepsis].

PMID- 16089015
TI  - [Acute confusional state associated with prosthetic vascular graft infection].

PMID- 16089016
TI  - [Spontaneous bacterial peritonitis as the presenting form of colon
      adenocarcinoma].

PMID- 16089017
TI  - [Hypothyroidism and lovastatin-induced myositis].

PMID- 16089018
TI  - [Hepatic hydrothorax].

PMID- 16089019
TI  - [Pyomyositis in diabetic patient].

PMID- 16089020
TI  - [Arthritis tuberculosis].

PMID- 16089021
TI  - The development of penicillin: genesis of a famous antibiotic.

PMID- 16089022
TI  - The hidden costs of environmentally responsible health care.

PMID- 16089023
TI  - Opportunistic infections as causes of death in HIV-infected patients in the HAART
      era in France.
AB  - The objective of the study was to describe the underlying causes of death of HIV
      infected patients in the HAART era and to focus on those related to opportunistic
      infection (OI), in a national multicentre study ('Mortalite 2000'). A total of
      964 deaths were recorded and 924 cases were available for analysis. Underlying
      cause of death were AIDS-related (47%), viral hepatitis (11%), non-AIDS cancers
      (11%), cardiovascular diseases (7%) and others (11%). Among patients who died of
      AIDS events, 262 (27%) died of at least one OI. OIs reported at the time of death
      were Cytomegalovirus infection 67 times, Pneumocystis jiroveci pneumonia 56,
      disseminated Mycobacterium avium intracellulare infection 53 and cerebral
      toxoplasmosis 48. Compared to patients who died of other causes, patients who
      died of OIs were younger and more likely to be infected through heterosexual
      contact, in poor socioeconomic conditions, migrants, more recently diagnosed for
      HIV infection, and naive of antiretroviral therapy and OI prophylaxis. OIs are
      still a major cause of death in HIV-infected patient in the HAART era, especially
      among patients recently diagnosed for HIV infection and who do not have access to
      care, as well as in long term infected patients where prophylaxis should be
      revisited.

PMID- 16089024
TI  - Mental health and juvenile justice: moving toward more effective systems of care.
AB  - This issue brief discusses the mental health needs of youth who are involved with
      the juvenile justice system, how they come into contact with the system, and the
      evidence of the availability and quality of mental health services for such
      youth. The paper also explores public policy options for avoiding dependence on
      the juvenile justice system as a last resort for treating youth with mental
      disorders.

PMID- 16089025
TI  - Patient education. Asthma first aid for your child.

PMID- 16089026
TI  - [Endobronchial foreign body due to an injury].

PMID- 16089027
TI  - COPD rehabilitation: the acid test.

PMID- 16089028
TI  - Emerging of admitted pneumonia after tsunami in Phuket, Thailand.

PMID- 16089029
TI  - Re: Whitelaw W. Oxygen therapy, then and now. Can Respir J 2005;12:67-8.

PMID- 16089030
TI  - Ethics self-assessment.

PMID- 16089031
TI  - Siemens shows its U.S. face.

PMID- 16089032
TI  - Microsatellite diversity within Oryza sativa with emphasis on indica-japonica
      divergence.
AB  - The molecular evolution of cultivated rice Oryza sativa L. has long been a
      subject of rice evolutionists. To investigate genetic diversity within and
      differentiation between the indica and japonica subspecies, 22 accessions of
      indica and 35 of japonica rice were examined by five microsatellite loci from
      each chromosome totalling 60 loci. Mean gene diversity value in the indica rice
      (H=0.678) was 1.18 times larger than in the japonica rice (H=0.574). Taking the
      sampling effect into consideration, average allele number in the indica rice was
      1.40 times higher than that in the japonica rice (14.6 vs 10.4 per variety).
      Chromosome-based comparisons revealed that nine chromosomes (1, 2, 3, 4, 5, 8, 9,
      10 and 11) harboured higher levels of genetic diversity within the indica rice
      than the japonica rice. An overall estimate of F(ST) was 0.084-0.158, indicating
      that the differentiation is moderate and 8.4-15.8% of the total genetic variation
      resided between the indica and japonica groups. Our chromosome-based comparisons
      further suggested that the extent of the indica-japonica differentiation varied
      substantially, ranging from 7.62% in chromosome 3 to 28.72% in chromosome 1.
      Cluster analyses found that most varieties formed merely two clusters for the
      indica and japonica varieties, in which two japonica varieties and five indica
      varieties were included in the counterpart clusters, respectively. The 12
      chromosome-based trees further showed that 57 rice varieties cannot be clearly
      clustered together into either the indica or japonica groups, but displayed
      relatively different clustering patterns. The results suggest that the process of
      indica japonica differentiation may have proceeded through an extensive
      contribution by the alleles of the majority in the rice genome.

PMID- 16089033
TI  - Response to selection for rapid chill-coma recovery in Drosophila melanogaster:
      physiology and life-history traits.
AB  - Resistance to low temperatures can vary markedly among invertebrate species and
      is directly related to their distribution. Despite the ecological importance of
      cold resistance this trait has rarely been studied genetically, mainly because
      low and variable fitness of offspring from cold-stressed mothers makes it
      difficult to undertake selection experiments and compare cold resistance of
      parents and offspring. One measure of cold resistance that varies geographically
      in Drosophila melanogaster and that is amenable to genetic analysis is chill-coma
      recovery. Three replicate lines of D. melanogaster were selected every second
      generation, for over 30 generations, for decreased recovery time following
      exposure to 0 degrees C. Correlated responses were scored to characterize
      underlying physiological traits and to investigate interactions with other
      traits. Lines responded rapidly to the intermittent selection regime with
      realized heritabilities varying from 33% to 46%. Selected lines showed decreased
      recovery time after exposure to a broad range of low temperatures and also had a
      lower mortality following a more severe cold shock, indicating that a general
      mechanism underlying cold resistance had been selected. The selection response
      was independent of plastic changes in cold resistance because the selected lines
      maintained their ability to harden (i.e. a short-term exposure to cool
      temperature resulted in decreased recovery time in subsequent chill-coma assays).
      Changes in cold resistance were not associated with changes in resistance to high
      temperature exposure, and selected lines showed no changes in wing size,
      development time or viability. However, there was a decrease in longevity in the
      selected lines due to an earlier onset of ageing. These results indicate that
      chill-coma recovery can be rapidly altered by selection, as long as selection is
      undertaken every second generation to avoid carry-over effects, and suggest that
      lower thermal limits can be shifted towards increased cold resistance
      independently of upper thermal limits and without tradeoffs in many life-history
      traits.

PMID- 16089034
TI  - Evolutionary history of the Drosophila bipectinata species complex.
AB  - Groups of recently diverged species offer invaluable glimpses into the history
      and genetic basis of speciation and phenotypic evolution. In this report, we
      combine phylogenetic and population-genetic approaches to reconstruct the
      evolutionary history of the Drosophila bipectinata species complex. This complex
      is a group of four closely related, largely sympatric species--D. bipectinata, D.
      parabipectinata, D. malerkotliana and D. pseudoananassae. Using the sequences of
      one mitochondrial and six nuclear loci, we show that D. bipectinata and D.
      parabipectinata are the two most closely related species, and that together with
      D. malerkotliana they form a monophyletic clade to which D. pseudoananassae is a
      relatively distant outgroup. Genetic divergence among D. bipectinata, D.
      parabipectinata and D. malerkotliana is extremely low, and we estimate that these
      species diverged only 283,000-385,000 years ago. We also find that mitochondrial
      DNA shows evidence of recent gene flow across species boundaries. Despite the low
      genetic divergence, species of the bipectinata complex show an unusually high
      degree of morphological differentiation. This contrast underscores the importance
      of understanding the genetic basis of functional differentiation among closely
      related species.

PMID- 16089035
TI  - Comparative losses of quantitative and molecular genetic variation in finite
      populations of Drosophila melanogaster.
AB  - Quantitative genetic variation, the main determinant of the ability to evolve, is
      expected to be lost in small populations, but there are limited data on the
      effect, and controversy as to whether it is similar to that for near neutral
      molecular variation. Genetic variation for abdominal and sternopleural bristle
      numbers and allozyme heterozygosity were estimated in 23 populations of
      Drosophila melanogaster maintained at effective population sizes of 25, 50, 100,
      250 or 500 for 50 generations, as well as in 19 highly inbred populations and the
      wild outbred base population. Highly significant negative regressions of
      proportion of initial genetic variation retained on inbreeding due to finite
      population size were observed for both quantitative characters (b = -0.67 +/-
      0.14 and -0.58 +/- 0.11) and allozyme heterozygosity (b = -0.79 +/- 0.10), and
      the regression coefficients did not differ significantly. Thus, quantitative
      genetic variation is being lost at a similar rate to molecular genetic variation.
      However, genetic variation for all traits was lost at rates significantly slower
      than predicted by neutral theory, most likely due to associative overdominance.
      Positive, but relatively low correlations were found among the different measures
      of genetic variation, but their low magnitudes were attributed to large sampling
      errors, rather than differences in the underlying processes of loss.

PMID- 16089036
TI  - Fine mapping of porcine chromosome 6 QTL and LEPR effects on body composition in
      multiple generations of an Iberian by Landrace intercross.
AB  - The leptin receptor gene (LEPR) is a candidate for traits related to growth and
      body composition, and is located on SSC6 in a region where fatness and meat
      composition quantitative trait loci (QTL) have previously been detected in
      several F2 experimental designs. The aims of this work were: (i) to fine map
      these QTL on a larger sample of animals and generations (F3 and backcross) of an
      Iberian x Landrace intercross and (ii) to examine the effects of LEPR alleles on
      body composition traits. Eleven single nucleotide polymorphisms (SNPs) were
      detected by sequencing LEPR coding regions in Iberian and Landrace pig samples.
      Three missense polymorphisms were genotyped by pyrosequencing in 33 F0, 70 F1,
      418 F2, 86 F3 and 128 individuals coming from the backcross of four F2 males with
      24 Landrace females. Thirteen microsatellites and one SNP were also genotyped.
      Traits analysed were: backfat thickness at different locations (BF(T)),
      intramuscular fat percentage (IMF(P)), eye muscle area (EM(A)), loin depth
      (LO(D)), weight of shoulder (SH(W)), weight of ribs (RIB(W)) and weight of belly
      bacon (BB(W)). Different statistical models were applied in order to evaluate the
      number and effects of QTL on chromosome 6 and the possible causality of the LEPR
      gene variants with respect to the QTL. The results support the presence of two
      QTL on SSC6. One, at position 60-100 cM, affects BF(T) and RIB(W). The other and
      more significant maps in a narrow region (130-132 cM) and affects BF(T), IMF(P),
      EM(A), LO(D), SH(W), RIB(W) and BB(W). Results also support the association
      between LEPR alleles and BF(T) traits. The possible functional implications of
      the analysed polymorphisms are considered.

PMID- 16089037
TI  - Marker densities and the mapping of ancestral junctions.
AB  - In any partially inbred population, 'junctions' are the loci that form boundaries
      between segments of ancestral chromosomes. Here we show that the expected number
      of junctions per Morgan in such a population is linearly related to the
      inbreeding coefficient of the population, with a maximum in a completely inbred
      population corresponding to the prediction given by Stam (1980). We further show
      that high-density marker maps (fully informative markers with average densities
      of up to 200 per cM) will fail to detect a significant proportion of the
      junctions present in highly inbred populations. The number of junctions detected
      is lower than that which would be expected if junctions were distributed randomly
      along the chromosome, and we show that junctions are not, in fact randomly
      spaced. This non-random spacing of junctions significantly increases the number
      of markers that is required to detect 90% of the junctions present on any
      chromosome: a marker count of at least 12 times the number of junctions present
      will be needed to detect this proportion.

PMID- 16089038
TI  - An entropy-based measure of founder informativeness.
AB  - Optimizing quantitative trait locus (QTL) mapping experiments requires a
      generalized measure of marker informativeness because variable information is
      obtained from different marker systems, marker distribution and pedigree types.
      Such a measure can be derived from the concept of Shannon entropy, a central
      concept in information theory. Here we introduce entropy-based founder
      informativeness (EFI), a new measure of information content generalized across
      pedigrees, maps, marker systems and mating configurations. We derived equations
      for inbred- and outbred-derived mapping populations. Mathematical properties of
      EFI include enhanced sensitivity to mapping population type and extension to any
      number of founders. To illustrate the use of EFI, we compared experimental
      designs for QTL mapping for three examples: (i) different marker systems for an
      F2 pedigree, (ii) different marker densities and sampling sizes for a BC1
      pedigree and (iii) a comparison of haplotypic versus zygotic analyses of an
      outbred pedigree. As an a priori generalized measure of information content, EFI
      does not require phenotypic data for optimizing experimental designs for QTL
      mapping.

PMID- 16089039
TI  - A grandfather's contradictory course.

PMID- 16089040
TI  - Peri-implant bone reaction to immediate, early, and delayed orthodontic loading
      in humans.
AB  - Seventeen endosseous titanium implants were placed in completely edentulous jaws
      of 15 patients. The implants were loaded immediately or after 2 or 6 months, with
      100 g orthodontic force. Three weeks later, the implants were removed and
      histologically analyzed. All of the immediately loaded implants, along with three
      of the eight that were loaded after 2 months, were lost. The remaining implants
      were stable until the end of the study. Histologic analysis of the retrieved
      implants showed bone remodeling in the cortical bone, thickening of the bony
      trabeculae by new lamellar bone deposition, and microcalli of woven bone or a
      lattice of woven bone formation around some implants that had been placed in soft
      bone. Tetracycline labeling revealed an elevated amount of newly formed bone. If
      further studies prove that a controlled application of orthodontic force, before
      application of occlusal loading, is able to rapidly enhance the density of soft
      peri-implant bone, we will have a powerful and precise tool to improve the rate
      of implant success.

PMID- 16089041
TI  - Implants in regenerated bone in patients treated for generalized aggressive
      periodontitis: a prospective longitudinal study.
AB  - The aim of this prospective longitudinal study of patients treated for
      generalized aggressive periodontitis (GAP) was the clinical, microbiologic, and
      radiologic longitudinal evaluation of implants placed into bone regenerated by
      the guided bone regeneration (GBR) technique. Ten patients with GAP who had lost
      either one or two maxillary incisors or premolars through periodontal disease and
      whose alveolar bone was neither high nor wide enough for implant placement were
      enrolled in the study. GBR was carried out in a two-stage procedure using
      titanium-reinforced extended polytetrafluoroethylene membranes and titanium
      screws. No bone graft or bone substitute materials were used. After 6 to 8
      months, the membranes and supporting screws were removed, and a total of 15
      implants (Nobel Biocare) were placed. The control group comprised 10
      periodontally healthy patients who had a total of II implants (Nobel Biocare)
      placed in the maxilla (incisor and premolar region) without GBR because of
      aplasia, trauma, or endodontic lesions. All patients were examined 2 to 4 weeks
      before extraction of the nonretainable teeth (baseline) and again immediately
      after placement of the superstructure. Further examinations were performed within
      the framework of a 3-month recall schedule over a 3-year period. At each session,
      clinical parameters (probing pocket depths, bleeding on probing, gingival
      recession, clinical attachment level, Gingival Index, and Plaque Index) were
      recorded at teeth and implants, and the composition of the subgingival microflora
      was determined by dark-field microscopy and DNA probe. Intraoral radiographs were
      taken for control purposes at baseline, immediately after insertion of the
      superstructure, and 1 and 3 years later. The GBR technique yielded a horizontal
      and vertical bone gain of 4.5 to 7.0 mm in the GAP patients. The clinical,
      microbiologic, and radiologic findings indicated healthy periodontal and
      periimplant conditions in both patient groups throughout the study. However, a
      slightly increased attachment loss (0.65 mm) and bone loss (1.78 mm) were
      recorded at the implants in the regenerated bone after 3 years of loading. The 3
      year implant survival rate was 100% in both groups. The possibility of continuous
      attachment loss and bone loss occurring at teeth and implants in regenerated bone
      cannot be ruled out in patients treated for aggressive periodontitis. The
      prognosis for the retention of the teeth and implants is thus open to question.

PMID- 16089042
TI  - Clinical considerations for densely sintered alumina and zirconia restorations:
      part 2.
AB  - Part 1 of this series provided the foundation for understanding the nature of
      densely sintered alumina- and zirconia-based restorations, provided guidelines
      for case selection, and addressed framework design considerations. This article
      discusses guidelines for lamination of the densely sintered alumina- and zirconia
      based restorations and proper try-in, and examines options for conventional and
      adhesive luting procedures.

PMID- 16089043
TI  - The use of intraorally harvested autogenous block grafts for vertical alveolar
      ridge augmentation: a human study.
AB  - This study presents a clinical, radiographic, laboratory, and
      histologic/histomorphometric analysis of the use of mandibular block autografts
      for vertical alveolar ridge augmentation. Twelve patients were included in the
      study. The autogenous block autografts were fixated at the recipient sites with
      screws, and a mixture of autogenous bone marrow and inorganic bovine mineral (Bio
      Oss) was used at the periphery. At re-entry surgery, all the grafts appeared well
      incorporated at the recipient sites. Radiographic measurements revealed an
      average of 5.75 +/- 1.29 mm vertical ridge augmentation at 1 month after surgery
      and 4.75 +/- 1.29 mm at 4 to 6 months after surgery. This indicated 17.4%
      resorption. Laboratory volumetric measurements revealed an average of 0.84 +/-
      0.34 mL of alveolar ridge augmentation 1 month after surgery and 0.71 +/- 0.28 mL
      at 6 months postoperatively. The resorption rate according to the laboratory
      volumetric measurements was 15.5%. Linear laboratory measurements revealed 5.92
      +/- 1.38 mm of vertical ridge augmentation 1 month postoperatively and 4.08 +/-
      1.01 mm at 4 to 6 months after surgery. Histologic evaluation of the block
      autografts indicated signs of active remodeling activity in 10 of the 12
      specimens. In one case the block graft became exposed and infected, and in
      another case the block autograft became dislodged during implant placement
      surgery. Histomorphometric analysis of the peripheral particulate bone indicated
      bone present at 33.99% +/- 8.82% of the graft surface, while 42.43% +/- 11.06% of
      the area was occupied by fibrous tissue and 23.89% +/- 9.12% was made up of
      residual Bio-Oss particles. Residual Bio-Oss particles were in tight contact with
      newly formed bone along 58.57% +/- 15.22% of their perimeter.

PMID- 16089044
TI  - Three-dimensional micro-computed tomographic evaluation of periodontal
      regeneration: a human report of intrabony defects treated with Bio-Oss collagen.
AB  - This study utilized three-dimensional micro-computed tomography (micro-CT) to
      evaluate the regenerative response to Bio-Oss Collagen when used alone or in
      combination with a Bio-Gide bilayer collagen membrane for the treatment of four
      intrabony defects (5 to 7 mm) around single-rooted teeth. The micro-CT
      observations are compared to the clinical, radiographic, and histologic results,
      which have been previously reported. After reflecting a full-thickness flap,
      thorough degranulation and root planing were accomplished. Bio-Oss Collagen was
      then used to fill the defects, and in two cases a Bio-Gide membrane was placed
      over the filled defect. Radiographs, clinical probing depths, and attachment
      levels were obtained before treatment and immediately preceding en bloc resection
      of teeth and surrounding tissues 9 months later. A mean pocket depth reduction of
      5.75 mm and mean clinical attachment level gain of 5.25 mm were recorded. The
      histologic evaluation demonstrated the formation of a complete new attachment
      apparatus with new cementum, periodontal ligament, and alveolar bone at the level
      of and coronal to the calculus reference notch. Micro-CT evaluation confirmed the
      histologic results and demonstrated the absence of ankylosis or root resorption
      for all specimens. This human histologic study demonstrated that Bio-Oss Collagen
      has the capacity to facilitate regeneration of the periodontal attachment
      apparatus when placed in intrabony defects. Micro-CT observations confirmed the
      histologic results and enhanced the three-dimensional understanding of
      periodontal wound healing. The results indicate that micro-CT may be useful for
      three-dimensional evaluation of periodontal regenerative procedures.

PMID- 16089045
TI  - Mobilization of the inferior alveolar nerve with simultaneous implant insertion:
      a new technique. Case report.
AB  - For reconstruction of an atrophied posterior mandible, different therapeutic
      options have been proposed, such as autologous bone grafting, guided bone
      regeneration for vertical ridge augmentation, and inferior alveolar nerve (IAN)
      mobilization with simultaneous implant placement. The possible dehiscence of soft
      tissues covering the surgical zone makes the first and second techniques
      unpredictable. Moreover, two surgical sites are necessary and a long treatment
      time is required (about 12 months). With IAN mobilization, only one surgical
      intervention is required and the total treatment time is shorter (about 6
      months). However, this technique risks irreversible damage to the IAN, with
      consequent functional alterations. Current studies have shown extreme variability
      in the examination of functionality of the neurovascular bundle after its
      mobilization. This variability can be attributed both to the methodology used for
      the tests, which evoke subjective answers from the patient, and to the surgical
      procedure, which is highly dependent on operator technique. Nerve damage can be
      the result of an overstretched mucoperiosteal flap in the premolar area to
      achieve optimal visibility of the surgical zone. This article reports a case in
      which a new surgical approach to IAN mobilization is performed using a
      specifically engineered device for simplified bone surgery (Mectron
      Piezosurgery). This device enables the surgeon to cut hard tissue without
      injuring the soft tissues. Therefore, there is a lower risk of damaging the IAN,
      and it is possible to reduce overstretching of the mental nerve by creating a
      smaller bone window and using an apicocoronal inclination of instruments to
      capture the neurovascular bundle.

PMID- 16089046
TI  - The use of a resin-bonded fixed splint in periodontally compromised mandibular
      anterior teeth: a case report.
AB  - In the treatment of patients with severe periodontal disease, it is becoming
      possible to re-establish a healthy and well-functioning dentition through
      interdisciplinary dental teamwork. This article presents a case using a resin
      bonded splint for stabilizing periodontally compromised mandibular anterior teeth
      after orthodontic treatment. A 30-year-old woman came to the authors with severe
      periodontitis, which had resulted in spacing of the anterior teeth and tipping of
      the posterior teeth. Periodontal-orthodontic treatment was combined with
      prosthodontic reconstruction, and a resin-bonded splint extending from canine to
      canine was placed for postorthodontic stabilization of the periodontally
      compromised teeth. No debonding of the splint occurred, and no further
      periodontal invasion was found in this case after 4 years of follow-up.

PMID- 16089047
TI  - Immediate substitution of central incisors with an unusual enamel paraplasia by a
      newly developed titanium implant: a case report.
AB  - The replacement of incisors with an unfavorable hard and soft tissue environment
      in the maxilla can be a challenging procedure in terms of esthetic outcome. The
      present report describes the replacement of two hopeless central incisors by
      newly developed titanium implants (TE Implant, Straumann) for immediate
      placement. This type of implant was chosen to compensate for the natural
      esthetics, which became compromised because of periodontitis and an unusual root
      anatomy. Both incisors presented with an atypical enamel paraplasia characterized
      by a circumferential enamel projection in apical direction. The consequence was a
      markedly reduced surface for periodontal attachment. Two weeks after implant
      placement, two acrylic resin crowns were cemented onto the new temporary titanium
      abutments. Five months later, the definitive prosthetic restoration was processed
      by porcelain pressed onto galvanic-cap crowns, which were cemented to standard
      wide-neck abutments. Control radiographs showed uneventful healing.

PMID- 16089048
TI  - Fabrication of a surgical template for implant/bar-retained mandibular
      overdentures.
AB  - To achieve long-term success with an implant-retained overdenture, application of
      force in the path of insertion of the prosthesis has been recommended. This
      implies that the retentive matrices and the implants are positioned parallel to
      each other and to the path of insertion of the prosthesis. This article describes
      a technique for the fabrication of a surgical template for an implant-retained
      overdenture in the mandible. Adherence to the guidelines proposed in this article
      will lead to optimal implant placement in a consistent and repeatable manner.

PMID- 16089049
TI  - Pressure ulcer prevention and care: preventing and managing pressure ulcers in
      long-term care: an overview of the revised federal regulation.
AB  - Although the Centers for Medicare and Medicaid Service's Federal Regulation as it
      relates to pressure ulcer prevention and care in long-term care facilities has
      not changed, the Guidance to Surveyors (F-314) has been expanded significantly.
      In addition to more clearly defining commonly used terms, the new guidance
      document emphasizes the use of pressure ulcer risk assessment and prevention
      strategies, pain assessment and treatment, and monitoring the care outcomes. The
      Centers for Medicare and Medicaid Service has clearly raised the bar on pressure
      ulcer care. Based on currently available evidence, the guidance document is clear
      in its intent to encourage all long-term care facilities to adopt evidence-based
      pressure ulcer protocols of care. This transition, and the development and
      implementation of this guidance document, may present considerable challenges to
      some long-term care facilities. However, the lack of ambiguity in the F-314
      document and its consistency with currently available evidence may be helpful to
      staff and improve outcomes of care.

PMID- 16089050
TI  - Pressure ulcer prevention and care: implementing the revised guidance to
      surveyors for long-term care facilities.
AB  - The revised guidelines for long-term care surveyors by the Centers for Medicare
      and Medicaid Services link the existing pressure ulcer prevention and treatment
      evidence base with federal guidelines. The guidance document is detailed and
      attempts to ensure that residents receive optimal care to help prevent and manage
      these wounds. Implementation of the guidance document recommendations requires a
      complete review, and possibly revision, of existing policies and procedures.
      Understanding the background, rationale, and methods to implement these
      recommendations will help administrators and clinicians develop protocols of care
      that are effective, cost efficient, and comply with the new guidelines.

PMID- 16089051
TI  - Passion in practice.

PMID- 16089052
TI  - Psychological adjustment after ostomy surgery: what do we know?

PMID- 16089053
TI  - Silicone net dressing as an adjunct with negative pressure wound therapy.

PMID- 16089054
TI  - Law & order PUF: pressure ulcer forensics.

PMID- 16089055
TI  - Living with a necrotic wound: a clinician's personal journey.

PMID- 16089056
TI  - A spring mix of news.

PMID- 16089057
TI  - The NPUAP Dual Mission Conference: reaching consensus on staging and deep tissue
      injury.

PMID- 16089058
TI  - AAWC submits comments to the MCAC on usual care of chronic wounds.

PMID- 16089059
TI  - Computer-based testing of the Braden Scale for Predicting Pressure Sore Risk.
AB  - The Detroit Medical Center nursing documentation system requires all staff nurses
      to complete the Braden Scale for Predicting Pressure Sore Risk on an Acute Care
      Flow Record or Critical Care Flow Sheet on every patient, every day. An audit of
      these records raised concern as to whether staff nurses accurately used the
      Braden Scale to calculate pressure sore risk. Advanced Practice and ET Nurses
      noted that staff nurses were rating patients at lower levels of pressure sore
      risk than was warranted by the patient condition. In response, a computer-based
      learning module with case study examples was developed and tested to teach
      nursing staff to accurately evaluate pressure ulcer risk by using the Braden
      Scale and its subscales and to identify preventive interventions based on the
      patient's Braden subscale scores. Following revisions of those case study example
      narratives that were found to be problematic, the learning/assessment module was
      instituted in 2002. More than 2,500 nurses at the facility were tested regarding
      their knowledge of pressure ulcer risk assessment and prevention using this
      program. On average, nurses correctly rated the Braden Scale level of risk 75.6%
      of the time. The percentage of correct responses was highest for very high (92%)
      and very low (78%) levels of risk. This finding is consistent with the
      observation that most nosocomial pressure ulcers in this facility occur in
      patients who are rated in the "mild risk" level on the Braden scale. Subscales
      with the lowest percentage of correct answers were moisture and sensory
      perception. Correct clinical identification of a Stage I pressure ulcer as it was
      described in writing occurred only 53% of the time. These results indicate that
      training and practice are needed to use an assessment scale accurately. The
      Detroit Medical Center plans to include the Braden Scale in annual nursing
      education and competency testing.

PMID- 16089060
TI  - Managing wound care outcomes.
AB  - Chronic wounds increase home care costs, stressing an already overburdened
      system. To improve costs and wound outcomes of home care in Nova Scotia,
      dedicated home care professionals collaborated with the Nova Scotia Department of
      Health Clinical Issues Committee in a four-phase endeavor. In Phase I, a
      descriptive, retrospective chart review (1995-1999) was conducted using an
      Outcomes Management Model research framework to assess existing wound prevalence,
      costs, and outcomes of care in the Nova Scotia Home Care setting. In Phase II,
      using literature-based best available evidence, the Nova Scotia Standardized
      Prevention and Treatment Protocol was developed. In Phase III, the Protocol was
      disseminated to 20 Nova Scotia healthcare agencies educated on its use. Wound
      care outcomes and costs were measured in Phase IV using a prospective, quasi
      experimental, descriptive study design. The study found that before 1999, Nova
      Scotia Home Care wound care practices were costly and outdated, yielding
      sporadically recorded, often inferior, outcomes--eg, 30% of patients had pressure
      ulcers, 42% received daily home care visits, and of the 115 (24.6%) clients with
      venous leg ulcers only 16 received compression therapy. The Protocol increased
      awareness of the principles of moist wound healing and reduced the prevalence of
      chronic wounds, dressing change frequency, healing time, and costs of care. Phase
      IV study results (n = 50) showed an average decline in labor and materials costs
      of dollar 946.64 per client per month after Protocol implementation. The Nova
      Scotia Protocol enables home care professionals to provide quality wound care and
      has since been issued as policy for Home Care in Nova Scotia.

PMID- 16089061
TI  - The effects of massage as a method to prevent pressure ulcers. A review of the
      literature.
AB  - General information about the effects of massage to prevent pressure ulcers is
      limited. A literature search was conducted to provide more detailed knowledge
      about the effects of massage in general and in preventing the development of
      pressure ulcers in particular. Using the keywords massage, rubbing, prevention of
      pressure ulcers/pressure ulcers, and paying particular attention to referenced
      articles yielded a summary of different manual massage techniques and
      indications/contraindications of this intervention for both healthy tissues and
      tissues in patients at risk for developing pressure ulcers. A careful review of
      this information; the clinical, physical, and pathophysiological aspects of
      pressure ulcers, including extrinsic and intrinsic factor; and the time-pressure
      relationship suggests that one type of massage may be beneficial for persons who
      are at risk for developing pressure ulcers. Specifically, effleurage applied with
      moderate pressure is the most preferred massage in the treatment of pressure
      ulcers, although based on currently existing studies, it cannot be proven
      statistically that massage is an adequate preventive method for pressure ulcers.
      Although many guidelines advised against use of massage in people at risk for
      pressure ulcers, current evidence suggests that research to increase knowledge
      about the mechanism behind the effects of massage as part of an individualized
      prevention and treatment plan should be conducted.

PMID- 16089062
TI  - It's not just a wound...
AB  - An ongoing challenge in wound management is a belief that wounds are temporary,
      routine, and merely physical. However, wounds can be very complex ethically
      which, in turn, necessitates careful and sensitive attention by practitioners.
      Five clinical cases are analyzed in terms of their ethical and legal
      implications. More specifically, concepts such as informed consent, surrogate
      decision-making, compliance, intimacy, embodiment, stigma, and bodily memory are
      examined. Following the conceptual analyses are recommendations for responsive
      clinical practice.

PMID- 16089063
TI  - A summary of posters presented at the Symposium on Advanced Wound Care: 2003 and
      2004.
AB  - Poster topics and study designs presented at the 2003 and 2004 Symposium on
      Advanced Wound Care were summarized and compared to gain insight into current
      wound care developments and trends. The percentage of product-related posters
      increased from 54% in 2003 to 76.5% in 2004. The greatest increase was observed
      in the so-called physical treatment modalities category (eg, vacuum-assisted
      closure, electrical stimulation). They represented 11% of poster topics in 2003
      compared to more than 25% in 2004. The proportion of laboratory research studies
      presented decreased from 25% to 10% of posters while the percentage of clinical
      case studies increased from 40% to 50%. These observations may provide useful
      information to clinicians and manufacturers.

PMID- 16089064
TI  - Development of imageless computer navigation for acetabular component position in
      total hip replacement.
AB  - The purpose of this study was to develop an imageless (without preoperative
      computerized tomography (CT) scans or intraoperative fluoroscopy) computer
      navigation system for total hip replacement. One-hundred and ninety-five hips
      were operated with imageless computer navigation. Eighty-five hips were operated
      prior to obtaining precise results, with precision refined in the subsequent 110
      hips. Computer accuracy for cup-adjusted anteversion was achieved in 100% of the
      final 40 hips, and for adjusted inclination in 96.6%. The factors necessary for
      accurate measurements are mechanical stability of the tools with the light
      emitting diodes, adjusted computer anteversion and inclination for the tilt of
      the pelvis (tilt in the AP plane), and check-and-balance techniques for
      confirmation of measurements of tilt, anteversion and inclination.

PMID- 16089065
TI  - The clinical performance of metal-on-metal as an articulation surface in total
      hip replacement.
AB  - The metal-on-metal articulations in total hip arthroplasty (THA) were widely used
      between 1960 and 1975. The McKee-Farrar and other first-generation prostheses
      failed at a high rate because impingement caused early component loosening. The
      problem of early component loosening was corrected by improved component design
      and better manufacturing quality. Second-generation metal-on-metal total hip
      replacements have experienced short and medium-term success as assessed by Harris
      Hip Scores and patient self-assessment. The combined annual linear wear of the
      metal-on-metal femoral head and acetabular insert is less than 10 mm and
      osteolysis has only rarely been observed in association with well-fixed metal-on
      metal total hip replacements. Hypersensitivity is not a common cause of loosening
      with second-generation hip replacements and remains to be proven as a definitive
      diagnosis in unusual cases of unexplained pain. More than 40 years of use has
      demonstrated no increase in the incidence of renal failure or cancer in patients
      with metal-on-metal total hip replacements. The scientific evidence of the
      results using the metal-on-metal articulations would recommend its continued use
      in any patient who does not have compromised renal function.

PMID- 16089066
TI  - Does smoking affect implant survivorship in total hip arthroplasty? A preliminary
      retrospective case series.
AB  - This retrospective study aimed to explore the effects of smoking on hip implant
      survivorship. The study included 147 patients (165 hips) from 1985 to 1991 who
      underwent total hip arthroplasty (THA) with a particular uncemented cup, and
      either a cemented or uncemented femoral component of the same design. Thirty-one
      patients (34 hips, 21 percent of study group) smoked at the time of surgery. Of
      13 components (seven cups, five cemented and one cementless stem) revised for
      aseptic loosening, eight (8/68, 11.8 percent) were revised in six smokers, and
      five (5/262, 1.9 percent) were revised in four nonsmokers (p = 0.0012).
      Multivariate covariate analysis revealed a 4.5 times greater risk of implant
      loosening in smokers (p = 0.0662). Based on this preliminary study, further
      larger studies should be performed to determine the extent that smoking may
      contribute to THA survivorship.

PMID- 16089067
TI  - Early attempts at hip arthroplasty--1700s to 1950s.
AB  - Over the last three centuries, treatment of hip arthritides has evolved from
      rudimentary surgery to modern total hip arthroplasty (THA), which is considered
      one of the most successful surgical interventions ever developed. We here review
      the history of the early hip arthroplasty procedures for hip arthritis that
      preceded Charley total hip arthroplasty. An evaluation of such past enterprises
      is relevant, and reminds us of the ephemeral nature of human industriousness, and
      how medical research and procedures are not isolated developments, but correlate
      to the social, economical, and cultural framework of their time.

PMID- 16089068
TI  - A historical and economic perspective on Sir John Charnley, Chas F. Thackray
      Limited, and the early arthoplasty industry.
AB  - In the 1960s, Sir John Charnley pioneered modern total hip arthroplasty (THA) and
      spent the next two decades refining all aspects of the procedure, working with
      the commercial firm of Chas F. Thackray Limited, now a subsidiary of DePuy
      Orthopaedics, a Johnson and Johnson Company. We review here that relationship, in
      light of the complex relationships today that exist among industry, researchers,
      surgeons, and the public.

PMID- 16089069
TI  - Total hip arthroplasty and rehabilitation in ambulatory lower extremity amputees-
      a case series.

PMID- 16089070
TI  - Case report: Salmonella infection following total hip arthroplasty.
AB  - A case of a total hip arthroplasty infection with Staphylococcus aureus, co
      infected with Salmonella choleraesuis was treated with two-stage exchange and
      administration of vancomycin and ciprofloxacin. No signs of re-infection have
      appeared fourteen months after surgery. Cases of salmonella infection of hip
      prostheses are quite rare, with only a handful of reports in the literature.

PMID- 16089071
TI  - Epidemiology of ankle arthritis: report of a consecutive series of 639 patients
      from a tertiary orthopaedic center.
AB  - The purpose of our study was to identify the cause of symptomatic ankle arthritis
      in a consecutive series of patients presenting in a tertiary care setting.
      Between 1991 and 2004, 639 patients with Kellgren grade 3 or 4 ankle arthritis
      presented to the University of Iowa Orthopaedic Foot and Ankle Surgery service.
      The cause of the arthritis was determined based on medical history, physical
      examination, and imaging studies. To get a sense of the relative prevalence of
      the etiologies of lower extremity arthritis in our setting, we evaluated the
      cause of arthritis of all new patients presenting to the University of Iowa
      Orthopaedic Department from 1999-2004 with arthritis of the ankle, to those with
      arthritis of the hip or knee during one year. Of the 639 arthritic ankles, 445
      (70%) were post-traumatic, 76 (12%) were rheumatoid disease and 46 (7%) were
      idiopathic (primary osteoarthritis). The post-traumatic ankle arthritis patients
      were most commonly associated with past rotational ankle fractures. The majority
      of ankle arthritis is associated with previous trauma, whereas the primary cause
      of knee or hip arthritis is idiopathic. Unique strategies to prevent or treat
      post-traumatic ankle arthritis are needed.

PMID- 16089072
TI  - Salvage of diffuse ankle osteomyelitis by single-stage resection and
      circumferential frame compression arthrodesis.
AB  - Salvage of diffuse ankle osteomyelitis, especially in compromised hosts, is a
      challenging problem. The purpose of this report was to evaluate early
      complications and results using a standardized salvage protocol. Eight patients
      with diffuse ankle osteomyelitis were treated by resection of all infected
      tiissue and hybrid-frame compression arthrodesis. At presentation, five had open
      wounds. According to the Cierny/Mader classification, all had diffuse anatomic
      involvement and six of eight were compromised hosts. Seven had central distal
      tibial column involvement and one had primarily talar involvement. Surgical
      technique involved a two-inicision approach, removal of all infected materialand
      application of a compression circumferential frame with five thin wires across
      the foot, two across the tibia and two half-pins in the tibia. Fusion of eight
      ankles and four subtalar joints was attempted. All patients received six weeks of
      intravenous antibiotics. Open wounds were treated with wound vacuum assisted
      closure (VACs) devices until closure was achieved. Frames were removed at three
      months and walking casts were appliedfor one to two more months. Ankle sepsis was
      eradicated in all patients. Seven of eight ankles fused at an average of 13.5
      weeks (range, 10 to 16 weeks). One limb required below-knee amputation (BKA) at
      five weeks due to nonreconstructible vascular insufficiency. Three of four
      subtalar joints fused. Fixation problems included two pin-track infections
      cleared with oral cephalexin and one broken half-pin. Two diabetic Charcot
      patients required long-term ankle-foot orthosis (AFO) use due to subtalar
      instability. At average 3.4-year follow-up, none of the seven fused ankles has
      required further surgery. Use of this standardized salvage treatment protocol for
      these difficult problems in selected patients was effective with a relatively low
      associated complication rate.

PMID- 16089073
TI  - Systemic blastomycosis with osseous involvement of the foot: case report.
AB  - We report a patient who presented with three months of foot pain, lytic bone
      lesions in the foot, and a painless ipsilateral leg skin ulcer. Bone and skin
      biopsies revealed organisms compatible with Blastomyces. Systemic blastomycosis
      is rare, especially with bone involvement in the foot.

PMID- 16089074
TI  - Significant scoliosis regression following syringomyelia decompression: case
      report.
AB  - We present the case of a 5-year-old boy presenting with a 54-degree scoliosis
      secondary to a Chiari I malformation with a holocord syringomyelia extending from
      C1 to T10. Neurosurgical treatment involved posterior fossa craniectomy with
      decompression, and partial C1 laminectomy. At follow-up 7 years later, at age 12,
      radiographs revealed only a 4-degree scoliosis, and follow-up MRI revealed a
      deflated syrinx. We report this case to reveal the most significant scoliosis
      regression seen in our experience that may occur in younger patients after
      neurosurgical syringomyelia decompression for Chiari I hindbrain herniation.

PMID- 16089075
TI  - Evaluation, imaging, histology and operative treatment for dysplasia epiphysealis
      hemimelica (Trevor disease) of the acetabulum: a case report and review.
AB  - Dysplasia epiphysealis hemimelica (DEH), or Trevor's disease, is a rare disorder
      that most commonly affects the epiphysis of long bones in children. Rarely, major
      joints such as the hip can be involved. In this paper we describe a successfully
      treated case involving the acetabulum, documented with multiple imaging
      modalities, intraoperative photographs, histology, and follow-up radiographs.

PMID- 16089076
TI  - Case report: unusual tibia intramedullary osteoid osteoma in a two-year-old.
AB  - In this report, we discuss a case of a 30-month-old male presenting with a
      painful limp. Plain radiographic studies gave a preliminary diagnosis of a Brodie
      abscess. Further studies, including magnetic resonance imaging (MRI), were more
      consistent with that of an osteoid osteoma located within the tibial medullary
      canal, which is a rare location. The patient had an excisional biopsy. The final
      pathologic diagnosis confirmed intramedullary osteoid osteoma.

PMID- 16089077
TI  - Unicameral bone cysts of the pelvis: a study of 16 cases.
AB  - Unicameral bone cysts of the pelvis are extremely rare. This study summarizes the
      clinical, radiologic and pathologic features of 16 cases. Patients ranged in age
      from nine to 69. Most lesions were in the anterior portion of the iliac wing;
      many appeared to be related to an open iliac crest apophysis. This suggests that
      the pathogenesis of unicameral bone cysts in this portion of the ilium is similar
      to that seen in the proximal humerus and the proximal femur. The correct
      diagnosis was made preoperatively in only five cases. This indicates that,
      although they are well documented, unicameral bone cysts of the pelvis remain a
      diagnostic problem. Patients received a spectrum of treatments from curettage to
      observation. There appeared to be no difference in the outcome after any form of
      treatment. Therefore, unicameral bone cysts of the pelvis can be managed
      conservatively. The choice to manage patients conservatively depends on making
      the correct diagnosis based on clinical history and imaging. The most effective
      imaging is a combination of plain radiographs, computed tomography (CT) and
      magnetic resonance imaging (MRI).

PMID- 16089078
TI  - Severe periprosthetic cortical atrophy in the skeletally immature: a report of
      three cases.
AB  - We describe three patients who developed cortical bone atrophy around cemented
      endoprostheses used for partial femur reconstructions after resection of Ewing's
      sarcoma. We believe this to be related to remodeling secondary to stress
      shielding. Rather than increased porosity and decreased mineral density, the
      stress-shielding in these skeletally immature patients resulted in altered
      morphology of the cortical bone, with apparent maintenance of density.

PMID- 16089080
TI  - In vivo healing after capsular plication in an ovine shoulder model.
AB  - Traditionally, arthroscopic management of shoulder instability has been reserved
      for patients with isolated Bankart lesions without any capsular laxity or injury.
      To date, there are no animal studies evaluating the healing potential of capsular
      plication and/or capsulo-labral repair. The purpose of this in vivo animal study
      was to determine if the histological capsular healing of an open capsular
      plication simulating an arthroscopic plication is equivalent to the more
      traditional open capsular shift involving cutting and advancing the capsule.
      Twenty-six skeletally mature sheep were randomized to either an open capsular
      plication simulating arthroscopic plication (n = 13), or an open traditional
      capsular shift (n = 13). A sham operation (n = 4) was also performed involving
      exposure to visualize the capsule. Normal non-operated control shoulders were
      also analyzed. A pathologist blinded to the treatment evaluated both hematoxylin
      and eosin (H&E) sections and polarized light microscopy. Qualitative scoring
      evaluated fibrosis, mucinous degeneration, fat necrosis, granuloma formation,
      vascularity, inflammatory infiltrate and hemosiderin (0 to 3 points). Both the
      capsular plication and open shift groups demonstrated healing by fibrosis at the
      site of surgical manipulation. There were no statistical differences in the
      capsular healing responses between the two groups with regard to fibrosis,
      granuloma formation and vascularity. The open shift group demonstrated
      significantly more mucinous degeneration (p = 0.038). Fat necrosis was present in
      4/13 specimens in the open shift group and none in the capsular plication
      specimens. Both groups demonstrated disorganized collagen formation under
      polarized light microscopy. There were no differences between non-operated
      control specimens and sham surgery specimens. Our findings support the hypothesis
      that histologic capsular healing is equivalent between the plication group and
      the open shift group. In addition, the open shift group demonstrated
      significantly more changes indicative of tissue injury. This basic science model
      confirms capsular healing after simulated arthroscopic plication, providing
      support for arthroscopic capsular plication in practice.

PMID- 16089079
TI  - Joint contact stress: a reasonable surrogate for biological processes?
AB  - A joint's normal mechanical history contributes to the maintenance of articular
      cartilage and underlying bone. Loading facilitates the flow of nutrients into
      cartilage and waste products away, and additionally provides the mechanical
      signals essential for normal cell and tissue maintenance. Deleteriously low or
      high contact stresses have been presumed to result in joint deterioration, and
      particular aspects of the mechanical environment may facilitate repair of damaged
      cartilage. For decades, investigators have explored static joint contact stresses
      (under some more or less arbitrary condition) as a surrogate of the relevant
      mechanical history. Contact stresses have been estimated in vitro in many joints
      and in a number of species, although only rarely in vivo. Despite a number of
      widely varying techniques (and spatial resolutions) to measure these contact
      stresses, reported ranges of static peak normal stresses are relatively similar
      from joint to joint across species, and in the range of 0.5 to 5.0 MPa. This
      suggests vertebrate diarthrodial joints have evolved to achieve similar
      mechanical design criteria. Available evidence also suggests some disorders of
      cartilage deterioration are associated with somewhat higher peak pressures
      ranging from 1-20 MPa, but overlapping the range of normal pressures. Some
      evidence and considerable logic suggests static contact stresses per se do not
      predict cartilage responses, but rather temporal aspects of the contact stress
      history. Static contact stresses may therefore not be a reasonable surrogate for
      biomechanical studies. Rather, temporal and spatial aspects of the loading
      history undoubtedly induce beneficial and deleterious biological responses.
      Finally, since all articular cartilage experiences similar stresses, the concept
      of a "weight-bearing" versus a "non-weight-bearing" joint seems flawed, and
      should be abandoned.

PMID- 16089081
TI  - Use of a novel joint-simulating culture system to grow organized ex-vivo three
      dimensional cartilage-like constructs from embryonic epiphyseal cells.
AB  - A method for growth and maintenance of vital cartilaginous tissue is necessary
      for cartilage repair by in-vitro produced biologic implants. A previously tested
      perfusion system simulating joint activity was used. Whole epiphyses collected
      from thirty 11-day-old chick embryos were divided into two groups. One group was
      grown in a tissue culture dish for 10 days. The other group was placed in a
      perfusion system termed a joint-simulating device (JSD). After a period of 10
      days, histology and immunohistochemistry were performed on five epiphyses from
      each group. Histologically, epiphyses grown in the device coalesced into a
      homogenous three-dimensional mass. The bridging tissue between individual
      epiphyses was highly cellular (PCNA staining positive) and was composed of
      mesenchymal stem cells as shown by expression of FGF receptor 3. No such tissue
      formed between epiphyses in the tissue culture dish and the epiphyseal cores were
      shown to be necrotic. The rest of the epiphyses were evaluated for radioactive
      sulfate incorporation into glycosaminoglycans (GAGs). A tenfold increase in
      sulfate incorporation occurred in epiphyses grown within the JSD as compared to
      the traditional culture method. In conclusion, embryonic epiphyses could be a
      suitable source for the ex-vivo growth of tissue-engineered cartilage constructs
      that might later be used as an in-vivo cartilage implant. The joint simulating
      device effectively maintains cartilage viability and bioactivity for as long as
      10 days.

PMID- 16089082
TI  - A three-dimensional finite element model of the radiocarpal joint: distal radius
      fracture step-off and stress transfer.
AB  - Displaced intra-articular distal radius fractures are difficult to treat, with
      numerous associated complications. The potential onset of post-traumatic
      osteoarthritis (OA) is a major concern. The relationship between malreduced intra
      articular fracture of the distal radius and subsequent early onset of radiocarpal
      OA is clinically important, yet poorly understood. To better understand this
      presumed mechanical relationship, detailed information regarding joint loading,
      kinematics and associated stress distributions must be obtained. Toward this end,
      a three-dimensional finite element (3D FE) contact model of the radiocarpal joint
      has been developed, including the radius, lunate, scaphoid, articulations between
      these bones and selected soft tissues near the joint. FE model geometry was
      derived from cryomicrotome sections of a cadaver wrist. Radiocarpal contact
      stress distributions in the intact and simulated malreduced fracture conditions,
      previously collected using a cadaveric intra-articular fracture model, are used
      to establish validity of the computational model. Finally, a section of the
      distal radius constituting the entire lunate fossa was displaced 1,2 and 3 mm to
      represent a depressed lunate die-punch fracture.

PMID- 16089083
TI  - Quantification of the microstructural anisotropy of distraction osteogenesis in
      the rabbit tibia.
AB  - A longitudinal orientation of fibers and trabeculae has been observed
      histologically within distracted callus. This study quantified the intensity and
      angle of orientation of trabeculae within a distracted callus. Sixteen New
      Zealand white rabbits underwent unilateral tibial callus distraction with an
      external fixator across a mid-diaphyseal osteotomy. Included were: a seven-day
      postoperative latency period, ten days of distraction at 0.5 mm every 12 hours,
      and 20 days of post-distraction consolidation before euthanasia. Tibiae were
      removed, stripped of soft tissue, sectioned, and processed for decalcified
      histology. Micrographs of mid-coronal sections of the callus were evenly divided
      into 12 regions and underwent Fast Fourier Transform (FFT) analysis of the
      digitized image to determine the angle and intensity of the orientation of the
      bony trabeculae within the callus. The microstructure of the regenerate callus
      demonstrated an angle of orientation that uniformly matched that of cortical bone
      in all of regions of the callus and an intensity of orientation which approached
      that of cortical bone.

PMID- 16089084
TI  - In vivo longitudinal assessment of bone resorption in a fibular osteotomy model
      using micro-computed tomography.
AB  - Longitudinal in vivo micro-computerized tomography (CT) imaging was used to
      monitor bone resorption in a rat fibula osteotomy model. Quantitative image post
      processing techniques were developed for spatially aligning the longitudinal data
      sets. Nominal length and bone volume in the proximal and distal segments of the
      fibula after the osteotomy were measured, and quantitative comparisons of bone
      loss over a 13-week period post-surgery were made in five individual rats. A
      significant decrease in nominal length and bone volume of the distal segment was
      observed 13 weeks post surgery. A significant decrease in bone volume was also
      observed in the proximal segment. However, no change in nominal length was
      observed for the proximal segment of the fibula. This study illustrates the power
      of this non-invasive technology to measure in vivo small changes in bone length
      and volume using just a small cohort of animals.

PMID- 16089085
TI  - Effects of recombinant hematopoietins on blood-loss anemia in mice.
AB  - Use of recombinant human erythropoietin (rhEPO) for treatment of pre-operative
      anemia in anticipation of orthopaedic surgical blood loss has become a routine
      practice. Use of rhEPO to help manage unanticipated blood loss from elective
      surgery or major orthopaedic trauma is limited by the rate and volume of
      erythropoiesis that is achievable with exogenously administered rhEPO. The rate
      and volume of erythropoiesis may be limited by the available population of cells
      responsive to EPO. Cytokines known to affect these early hematopoietic
      progenitors may potentiate the effects of rhEPO. In this study, mice were
      rendered anemic by loss of approximately one-third of their total blood volume. A
      control group received only iron supplementation. Mice in three experimental
      groups received three injections of rhEPO. Two of these groups also received
      either recombinant murine stem cell factor (rmSCF) or recombinant murine
      interleukin-3 (rmIL-3). Both were before and in conjunction with rhEPO. Animals
      were sacrificed for peripheral blood testing at baseline, after initiation of
      rmSCF and rmIL-3 prior to rhEPO administration, and at three time points after
      dosing of rhEPO. Additionally, the bone marrow was harvested and cultured to
      determine the concentration of erythroid progenitors after treatment with rmIL-3
      or rmSCF, and after further treatment with rhEPO. Hematocrits were significantly
      higher in the first measurement point after administration of rhEPO in the groups
      receiving additional cytokines. The control and rhEPO-only groups were not
      different at this early time point. The maximal rate of erythropoiesis was also
      elevated in the groups receiving additional cytokines. The bone marrow of mice
      receiving SCF had a dramatically increased number of erythroid progenitors
      compared to all other groups. The population of EPO-responsive cells, dependent
      on cytokines not controlled by hypoxia, is a major rate-limiting and volume
      limiting factor in the response to rhEPO during recovery from blood-loss anemia.
      Administration of earlier-acting cytokines has the potential to increase the rate
      and volume of exogenously stimulated erythropoiesis.

PMID- 16089086
TI  - Cytogenetics of swarm rat chondrosarcoma.
AB  - The Swarm rat chondrosarcoma is a tumor tissue line derived from a tumor that
      arose spontaneously in a Sprague-Dawley rat. The original tissue has given rise
      to several tissue lines and cell lines that have been prepared in different
      laboratories. It has been observed that these lines differed in their growth
      rates and biochemical characteristics. We have characterized our Swarm rat
      chondrosarcoma tissue and cell lines currently in use in terms of their
      cytogenetic profiles and their tumorigenic properties in vivo. We found a wide
      variety of chromosomal abnormalities among cell lines, including translocations,
      deletions and polyploidy. There were also significant differences in their growth
      properties in vivo, giving rise to tumors of a few milligrams in the case of Ng
      cells, to 35 grams in the tissue line JWS. The cytogenetic complexity of the
      Swarm rat chondrosarcoma between and among different lines makes it very suitable
      to address questions about the changes that occur as a result of karyotypic
      abnormalities and to provide links between cytogenetic abnormalities and the
      dynamic oncogenic machinery.

PMID- 16089087
TI  - Limitations of isokinetic testing to determine shoulder strength after rotator
      cuff repair.
AB  - Some investigators have reported incomplete data when using isokinetic testing as
      a means of analyzing shoulder strength after rotator cuff repair. An explanation
      provided has been that the subjects could not reach the speed at which the
      machine was set. The purpose of this study was to determine if strength data
      could be generated for all motions being tested by using not only the one or two
      speeds employed by others, but three speeds across the spectrum of those
      available. Inclusion criteria were a minimum of two years since surgery with a
      normal contralateral shoulder. All eligible subjects had isokinetic testing of
      the non-operated shoulder followed by the operated shoulder, in flexion,
      abduction and external rotation, tested at 60 degrees, 120 degrees and 180
      degrees per second. Fourteen patients were eligible and tested. Isokinetic data
      showed deficiencies in strength in the operated shoulder compared to the opposite
      side for abduction, external rotation and flexion of 14%, 27% and 20%
      respectively. In 10/123 (8%) of the tests, the patients could not reach the
      preset velocity to yield valid data. One patient could not place and maintain the
      operated arm in the test position of 90 degrees of shoulder abduction. There was
      a significant deficiency in abduction at only one of three speeds. This study
      confirms that isokinetic testing is a powerful tool that lends itself well to
      producing objective data on shoulder strength after rotator cuff repair, but it
      also has the limitation that some patients cannot reach the preset velocity for
      some motions, or place and maintain the operated arm in the test position for the
      movements being tested. Therefore, to optimize the chances of obtaining
      isokinetic data for all movements after rotator cuff repair, we suggest using
      speeds for all motions and consideration of scapular, frontal and sagittal planes
      for testing.

PMID- 16089088
TI  - ACL tears in collegiate wrestlers: report of six cases in one season.
AB  - Six NCAA Division I wrestlers at The University of Iowa tore an anterior cruciate
      ligament (ACL) during the 2002-03 season. In comparison, between the years of
      1993 and 2002, only five wrestlers sustained the same injury. Retrospective
      review and video data analysis were performed. All six were injured while their
      knee was near terminal extension and in a vulnerable position. Eighty-three
      percent of all injuries occurred during takedowns. Five of the six wrestlers'
      mechanism of injury involved rotation and stress on the weight-bearing knee.
      Eighty-three percent sustained their injuries while their foot was firmly planted
      on the ground. Five of the injuries occurred in competition. Of the six wrestlers
      injured, four underwent immediate rehabilitation in hope of wrestling that same
      season. Three ultimately needed surgery and one continued to wrestle in the same
      season without having surgery. Of the five wrestlers who underwent surgical
      reconstruction of their ACL, each had bone-patellar-bone grafts.

PMID- 16089089
TI  - Direct arthroscopic distal clavicle resection: a technical review.
AB  - Degenerative change involving the acromioclavicular (AC) is frequently seen as
      part of a normal aging process. Occasionally, this results in a painful clinical
      condition. Although AC joint symptoms commonly occur in conjunction with other
      shoulder pathology, they may occur in isolation. Treatment of isolated AC joint
      osteoarthritis is initially non-surgical. When such treatment fails to provide
      lasting relief, surgical treatment is warranted. Direct (superior) arthroscopic
      resection of the distal (lateral) end of the clavicle is a successful method of
      treating the condition, as well as other isolated conditions of the AC joint. The
      following article reviews appropriate patient evaluation, surgical indications
      and technique.

PMID- 16089090
TI  - Rare bilateral femoral shaft stress fractures in a female long-distance runner: a
      case report.

PMID- 16089091
TI  - Patellofemoral realignment: dynamic intraoperative assessment.
AB  - We describe a method of dynamic assessment of patellar tracking intraoperatively
      during a Fulkerson osteotomy. We utilize an electrically conductive catheter
      intraopertively to directly stimulate the femoral nerve to cause quadriceps
      muscle contraction. The resultant active knee extension allows dynamic assessment
      of patellofemoral tracking prior to and after final Fulkerson fixation. This
      dynamic intraopertive technique allows us to approximate in vivo patellofemoral
      motion better than with passive motion assessment.

PMID- 16089092
TI  - Treatment of anterior femoroacetabular impingement with combined hip arthroscopy
      and limited anterior decompression.
AB  - Anterior femoroacetabular impingement results from abnormal abutment of the
      anterolateral femoral head-neck junction with the anterior acetabular-labral
      complex resulting in pain and progressive hip dysfunction. This under-recognized
      problem could be the manifestation of acetabular or proximal femoral deformity,
      and when left untreated leads to the development of osteoarthritis of the hip.
      Conservative treatment is usually unsuccessful and the optimal surgical treatment
      for these disorders needs to be determined. We present our technique for treating
      femoral (cam) impingement which combines hip arthroscopy and a limited open
      anterior head-neck osteoplasty as a less invasive and more conservative surgical
      approach, which still adequately addresses the anatomy and pathophysiology of
      this disease.

PMID- 16089093
TI  - A review of hip arthroscopy and its role in the management of adult hip pain.
AB  - The diagnosis and management of patients presenting with hip pain is often
      challenging. A thorough history and physical examination, imaging studies and
      selective injections can help define the source of pain in many of these
      individuals. As technology and technical skills continue to improve, the role for
      hip arthroscopy will continue to expand. Further well-designed studies will
      better refine the indications for hip arthroscopy in managing patients with hip
      pathology.

PMID- 16089094
TI  - A future model of musculoskeletal rehabilitation at the University of Iowa
      Hospitals and Clinics: spanning the continuum of care.
AB  - Models of rehabilitation care vary widely within academic medical centers, with
      most housing their own inpatient rehabilitation units. The University of Iowa
      Hospitals and Clinics focuses both on acute hospital inpatient and outpatient
      rehabilitation care instead of leaving rehabilitation to local community-based
      hospitals. This article discusses a method to provide adult inpatient
      rehabilitation care, and simultaneously provide specialized rehabilitation teams
      capable of spanning the entire continuum of rehabilitative care from admission at
      a Level I Trauma Center to the conclusion of successful outpatient rehabilitation
      needs. The costs of implementation of this plan can be justified by avoiding
      increased expenses already being incurred in addition to successful capture of
      outpatient rehabilitation revenues.

PMID- 16089095
TI  - Gluteus medius tendon rupture as a source for back, buttock and leg pain: case
      report.
AB  - A 67-year-old woman with chronic lumbosacral and hip symptoms involving gluteus
      medius tendon rupture and strain injury is presented here. We report her work-up
      and management. Although this is an uncommonly reported pathology, many patients
      with back, buttock and leg pain see physicians who often focus on lumbar spinal
      stenosis, lumbar radiculopathy or hip/knee osteoarthritis. Careful physical
      examination guided us to this patient's diagnosis.

PMID- 16089096
TI  - Bigelow's wire technique for a humeral shaft fracture: brief case report and
      historical perspective.
AB  - An older technique of limited open reduction and wire fixation was applied in the
      treatment of an open transverse humeral shaft fracture in a 14-year-old female.
      The original operative technique by H. Bigelow is described.

PMID- 16089097
TI  - A case series and review of salvage surgery for refractory humeral shaft nonunion
      following two or more prior surgical procedures.
AB  - The orthopedic surgery literature is replete with techniques for managing primary
      humeral shaft nonunions, with success rates upwards of 90 percent with plate
      fixation and autogenous bone grafting. Despite this success, persistent nonunion
      following one or more initial failed nonunion interventions can occur, imposing a
      significant clinical and surgical challenge. We report the application of a
      standard treatment protocol for refractory humeral shaft nonunions including
      optimization of patient co-morbidities in the peri-operative period, rigid 4.5mm
      compression plating with a minimum of eight cortices of fixation proximal and
      distal to the nonunion site, and utilization of autogenous bone grafting. This
      study, a retrospective review of seven patients, all managed based on this
      standard treatment protocol, revealed that all achieved fracture nonunion within
      six months of revision surgery. Six of seven patients were clinically satisfied
      with the outcome of surgery; one remained dissatisfied secondary to a chronic
      neuropathic pain syndrome. Although more complex surgical options such as
      Ilizarov external fixation and allograft cortical strut augmentation have been
      reported, and are available in the salvage situation of refractory humeral
      nonunions, we conclude strict application of basic nonunion principles can result
      in successful salvage of humerus nonunions in patients who have failed two or
      more prior surgical interventions.

PMID- 16089098
TI  - Normal leg compartment pressures in adult Nigerians using the Whitesides method.
AB  - In Caucasians, the range of normal intracompartmental pressure of the leg is from
      0 mmHg to 15 mmHg. In the literature, such measurements have not been done in
      Africa to identify normal leg intracompartmental pressures. We have sought to
      identify the normal range of pressures in such a population of Nigerians, and to
      demonstrate the reproducibility of the Whitesides injection technique with
      materials that are easily available in most hospitals so that compartment
      syndromes could be identified promptly and inexpensively in developing countries.
      We performed a 16-month hospital-based prospective study at Wesley Guild Hospital
      in Ilesa, Osun State, Nigeria, to measure the intracompartmental pressures in the
      anterior and deep posterior compartments of 49 contralateral uninjured legs of
      patients with closed contralateral tibial fractures, measured at presentation.
      The Whitesides infusion technique was used with the aim of determining the normal
      range of compartmental pressure in Nigerians. The anterior compartment pressures
      ranged from 3 mmHg to 18 mmHg with a mean 7.6 +/- 2.6 mmHg. The pressure in the
      deep posterior compartment ranged from 3 mmHg to 14 mmHg with mean of 7.4 +/- 2.7
      mmHg. The values are similar to those reported in the literature. There was no
      statistically significant difference between the pressures in the two
      compartments (p = 0.668).

PMID- 16089099
TI  - Scapholunate instability following dorsal wrist ganglion excision: a case report.

PMID- 16089100
TI  - Familial bilateral carpal tunnel syndrome in a Nigerian family: case report.

PMID- 16089101
TI  - Health status of non-Hispanic U.S.-born and foreign-born black and white persons:
      United States, 1992-95.
AB  - OBJECTIVE: This report describes differences in selected sociodemographic and
      health characteristics of the non-Hispanic U.S. population by race (black and
      white) and nativity (U.S-born and foreign-born), using data from the 1992-95
      National Health Interview Surveys (NHIS). METHODS: Data were collected for a
      household, multistage probability sample representative of the U.S. civilian
      noninstitutionalized population. A total of 456,729 persons were included in
      these analyses for the 4 data years combined. Statistics were age adjusted to the
      2000 U.S. standard population, and unadjusted estimates are also presented for
      comparison. RESULTS: Over 87 percent of the foreign-born black population
      assessed their health as being excellent or very good, significantly higher than
      U.S.-born black persons (52 percent), and similar to U.S.- and foreign-born white
      persons (69 percent for each group). Eleven percent of foreign-born black persons
      were limited in performing some type of activity, compared with 20 percent of
      their U.S.-born counterparts. Among white persons, 14 percent of foreign-born and
      16 percent of U.S.-born individuals were limited in activity. The foreign-born
      black population, especially women, had the lowest current smoking prevalence of
      all of the study groups. CONCLUSIONS: The data show significant differences in
      health characteristics between groups classified by race and nativity.
      Information about the nativity status of black and white populations may be
      useful in public health efforts to eliminate health disparities.

PMID- 16089102
TI  - [The demographic, perioperative and mortality characteristics of the Hungarian
      Liver Transplant Program].
AB  - INTRODUCTIONS: The authors summarize the demographic, morbidity and mortality
      characteristics of the Hungarian Liver Transplant Program. AIMS: They evaluate
      the changes and development, that has taken place with regard to indications,
      recipient population and characteristics, operation technique, and peroperative
      patient management. METHOD: In order to present the development, data are
      compared between two time periods (before and after 1999). The results are
      summarized on Tables and statistical Figures. Categorical variables are evaluated
      by chi2-test, continuous ones are with Levene Test (for homogeneity of means),
      Student T test and Mann-Whitney U-test. Cumulative survivals are computed with
      Kaplan-Meier log rank analysis. RESULTS: 194 primary liver transplantation have
      been performed. The hepatitis C was the leading indication from the beginning.
      Ten (10) liver transplantation have been performed in 1995, while 44 in 2004. The
      mortality within the first 2 months decreased from 24% to 5%. The 1, 3 and 5 year
      cumulative patient survival increased from 55%, 45% es 39% (1995-1997), to 72%,
      64% es 61% (1998-2000). Recently this is 78%, 77% es 77%. CONCLUSIONS: Between
      1995-1997 conventional liver transplantation became standard, while piggy back
      turned to be popular from 1998. From 1999 the HCV-PCR monitoring, the combined
      antiviral treatment, the UW perfusion of the donors took place. From 2003 we
      introduced the tailored immunosuppression, the steroid-free protocol for viral
      diseases. Total infused volume was decreased together with the amount of
      transfusion. The retrograde graft reperfusion (from the caval side) was
      introduced in 2004 together with the split technique in the liver transplantation
      and the rebirth of the pediatric program. The overall outcome of the
      retrospective analysis is, that the program has been developed to European
      standards with respect to its volume, technical capabilities and results.

PMID- 16089103
TI  - [The effect of chemo-radiotherapy on the remission and survival in patients with
      limited stage small cell lung cancer].
AB  - INTRODUCTION: The combined modality treatment used in case of limited stage small
      cell lung cancer assures the longest disease-free and average survival meanwhile
      maintaining an acceptable quality of life. OBJECT: The authors examined whether
      the combined modality treatment in case of limited-stage small cell lung cancer
      affects the remission positively or not: they presumed that the therapeutic
      response, early partial or complete clinical and oncological remission develops
      earlier than in patients treated with chemotherapy. The authors' other
      presumption was that the early therapeutic response could be the guarantee of the
      longest possible disease-free and average survival. PATIENTS AND METHOD: Small
      cell lung cancer (SCLC) was proved in 72 patients (23 women, 49 men, average 53
      year-olds) with histological and/or cytological examination. Having examined
      which stage the patients were in, they proved to be in the limited stage. The
      patients were divided into two groups at random: cytotoxic chemotherapy
      containing cisplatin + etoposide was used in 36 cases, meanwhile in the other 36
      cases the chemotherapy was completed with early concurrent thoracic radiotherapy.
      RESULTS: The therapeutic response happened earlier (early remission) in case of
      patients treated with chemo-radiotherapy than with chemotherapy treatment
      (average 10.4-12.6 weeks, SD = 1.22-1.99). The result of the "log rank" test
      showing the difference between the two groups is strongly significant in favor of
      the chemo-radiotherapy group (p = 0.0001). In patients with early remission
      receiving chemo-radiotherapy, the thoracic recidives and metastasis developed
      later (average 74.8 weeks, SD = 44.95), furthermore the average survival also
      proved to be longer (93.9 weeks, SD = 57.09). The average time until the
      development of tumor recidives and metastasis in patients belonging to the
      chemotherapy group was 44.5 weeks (SD = 30.23), and the average survival was 67.4
      weeks (SD = 32.77). The result of the "log rank" test proved significant
      advantage for the chemo-radiotherapy group both for disease-free survival (p =
      0.0010) and average survival (p = 0.0079 ). Another positive effect of chemo
      radiotherapy was that less thoracic recidives and central nervous system
      metastasis could be diagnosed. Examination of treatment toxicity showed that one
      has to count primarily with esophagitis and pneumonitis related to the
      radiotherapy in patients receiving chemo-radiotherapy.

PMID- 16089104
TI  - [Treatment of children's and adolescent's knee injuries].
AB  - INTRODUCTION: Authors made 162 knee arthroscopic operations due to hemarthrosis
      of the knee, acute knee blocking or acute developed instability on patients under
      18 years after knee injury during a 12 years period. The retrospective analysis
      of patient reports shows, that in 61.7% of the cases they found chondral- or
      osteochondral fracture in the knee. MATERIAL AND METHODS: On three dimensional
      routine X-ray pictures they were performed after the injury, in 85% of the cases
      fractures were not seen. Fortunately the most part of the hyalin surface injuries
      was smaller than 0.5 cm or were situated on less weight-bearing area only
      hemarthrosis evacuation and removing of loose body were done. If the
      osteochondral fractures was bigger than 0.5 cm or was broken from the weight
      bearing surface, they were fixed by KFI or Herbert-screws. When refixation of
      osteochondral fracture was not possible technically or in cases of chondral
      fractures, primary mosaic chondroplasty was used. The correct diagnosis and the
      early reconstruction of injured hyalin surface in childhood and teenagers is
      essential regarding to the function of the knee.

PMID- 16089105
TI  - [New intraoperative diagnostic methods parathyroid surgery. Adenoma localization
      by gamma probe].
AB  - INTRODUCTION: The key to heal primary hyperparathyroidism is to find the hyper
      functioning parathyroid gland(s). Promoting this the perioperative isotope guided
      localization technique is worldwide used in the last years. AIM: Authors use this
      method since February, 2000. They present their experiences. METHODS: At 122
      patients undergoing parathyroidectomy in last 5 years with diagnosis of primary
      hyperparathyroidism perioperative sestamibi scanning by gamma probe was taken to
      localize the adenoma. Tc-99m-sestamibi was administered 90-150 minutes before
      starting anesthesia. The distribution of activity was measured before operation
      percutaneously on the neck and during operation directly at explored parathyroid
      regions. Finally the removed specimens were ex vivo scanned. RESULTS: Because of
      the thyroid lobes also accumulate sestamibi the localizability of adenomas
      depended on direction of scanning. Important factor is the correct timing of
      isotope administration in order to achieve domination of parathyroid activity in
      time of measurement. Localization of adenomas by percutaneous measurement was
      correct in 36.1% of cases and by perioperative direct scanning in 66.4%.
      Furthermore, ex vivo scan of removed adenomas showed impressively high activity
      in all cases. CONCLUSIONS: In their experience sestamibi scanning lightens the
      operation only in a part of cases but probably it will be the most important
      method of localization if isotope selectively accumulating in parathyroid gland
      could be found. For the moment the greatest profit of this method is that the ex
      vivo measurement indicates the success of operation with great probability.

PMID- 16089106
TI  - [Hybridization and their application in the DNA array technology].
AB  - Hybridization and their application in the DNA array technology. DNA
      hybridization arrays measure simultaneously the expression of several genes.
      First, a known DNA sequence (probe) is fixed on a firm basis. Then the
      complementer sequence (target sequence) is linked to it during the hybridization
      process. The target sequence extracted from biological samples is fluorescently,
      enzimatically or radioactively labeled before detection. Higher expression
      results in higher signal in the detection system. Unlabeled DNA strands can also
      be detected, as the electronic and optical characteristics of the DNA is altered
      after complementer hybridization. In this review we summarize the basics of
      hybridisation and its newest application area in the DNA array systems.

PMID- 16089107
TI  - [Oncocytic tumor of the adrenal gland].
AB  - Oncocytic tumor of the adrenal gland. The authors describe a case of a rare tumor
      arising in the adrenal gland. The tumor 6 cm in diameter, connected to the right
      adrenal gland, was found incidentally in a healthy young man of 34 years of age,
      who suffered an accident and had a rib fracture. No pathological hormone
      production was detected on laboratory tests. The right adrenal gland with the
      tumor was removed by laparoscopic surgery. Histopathological examination revealed
      an oncocytic adenoma of the adrenal cortex. The authors describe the morphology
      and the differential diagnosis of this rare tumor of the adrenal gland.

PMID- 16089108
TI  - The anatomy of a pickle.

PMID- 16089109
TI  - When health policy is the problem: a report from the field.
AB  - We often think of health policy and health services research as offering
      solutions to cost, quality, and access problems. Many of us see health policy as
      simply ineffective. But any activity that has the power to cure can also do harm.
      Is it possible that the health policy enterprise has contributed to the very
      problems it has been attempting to eliminate? We argue that it has. Reasonable
      assumptions have led to a series of solutions that have provided political cover
      for those vested in the status quo. This process is nonpartisan, with those of us
      on the left and the right unintentionally and inadvertently contributing to the
      problems we are so committed to solving.

PMID- 16089110
TI  - Fostering rational regulation of patient safety.
AB  - After decades of inattention to the problem of medical injuries, patient safety
      is now occupying a prominent place on the health policy agenda and garnering
      renewed regulatory interest. Health care providers' behavior, with respect to
      patient safety and health care quality improvement, is now being shaped by top
      down regulation through statutes and administrative agency oversight, as well as
      bottom-up drivers such as tort litigation and the forces of the consumer-driven
      health care market. Patient safety today exemplifies that eclectic mix of
      regulation that can occur when a new problem is exposed to the general public; it
      also demonstrates the difficulties of coordinating regulatory signals from
      multiple sources and regulating incomplete information. This article reviews the
      evolution of the regulatory environment for patient safety, examines some of the
      tensions and challenges that currently define patient safety oversight, and
      suggests strategies for more rational and responsive regulation.

PMID- 16089111
TI  - The death of managed care: a regulatory autopsy.
AB  - On the heels of widespread patient protection legislation in the states, the
      managed care industry abandoned or greatly scaled back the core elements of gate
      keeping, utilization management, and financial incentives, which are the very
      targets of this legislation. This article explores whether, and to what extent,
      the industry's abrupt change in course can be attributed to these laws. Based on
      extensive interviews with key informants in six representative states, the
      article concludes that these laws were not the primary driver of changes in
      managed care practices. However, patient protection laws interacted with other
      social and market forces, through complex forms of feedback and reinforcement, to
      bring about more thoroughgoing change than would have otherwise occurred.

PMID- 16089112
TI  - The who, what, and why of risk adjustment: a technology on the cusp of adoption.
AB  - Risk adjustment (RA) consists of a series of techniques that account for the
      health status of patients when predicting or explaining costs of health care for
      defined populations or for evaluating retrospectively the performance of
      providers who care for them. Although the federal government seems to have
      settled on an approach to RA for Medicare Advantage programs, adoption and
      implementation of RA techniques elsewhere have proceeded much more slowly than
      was anticipated. This article examines factors affecting the adoption and use of
      RA outside the Medicare program using case studies in six U.S. health care
      markets (Baltimore, Seattle, Denver, Cleveland, Phoenix, and Atlanta) as of 2001.
      We found that for purchasing decisions, RA was used exclusively by public
      agencies. In the private sector, use of risk adjustment was uncommon and
      scattered and assumed informal and unexpected forms. The most common private
      sector use of RA was by health plans, which occasionally employed RA in
      negotiations with purchasers or to allocate resources internally among providers.
      The article uses classic technology diffusion theory to explain the adoption and
      use of RA in these six markets and derives lessons for health policy generally
      and for the future of RA in particular. For health policy generally, the
      differing experiences of public and private actors with RA serve as markers of
      the divergent paths that public and private health care sectors are pursuing with
      respect to managed care and risk sharing. For the future of RA in particular, its
      history suggests the need for health service researchers to consider barriers to
      use adoption and new analytic technologies as they develop them.

PMID- 16089113
TI  - When methods meet politics: how risk adjustment became part of Medicare managed
      care.
AB  - Health-based risk adjustment has long been touted as key to the success of
      competitive models of health care. Because it decreases the incentive to enroll
      only healthy patients in insurance plans, risk adjustment was incorporated into
      Medicare policy via the Balanced Budget Act of 1997. However, full implementation
      of risk adjustment was delayed due to clashes with the managed care industry over
      payment policy, concerns over perverse incentives, and problems of data burden.
      We review the history of risk adjustment leading up to the Balanced Budget Act
      and examine the controversies surrounding attempts to stop or delay its
      implementation during the years that followed. The article provides lessons for
      the future of health-based risk adjustment and possible alternatives.

PMID- 16089115
TI  - Superselective catheterization and embolization as first-line therapy for lower
      gastrointestinal bleeding.
AB  - Emergent operative intervention for lower gastrointestinal bleeding (LGIB) is
      associated with significant morbidity and mortality. Advances in endovascular
      techniques have made superselective catheterization and embolization (SSCE) of
      small visceral arterial branches possible. We hypothesized that SSCE for LGIB
      would be an effective first-line therapy and associated with low mortality. We
      identified all patients that underwent visceral angiography at our institution
      from 1997 to 2003. Records from all patients with documented LGIB and in whom
      SSCE was used as first-line therapy were reviewed. Twenty-three patients (69 +/-
      11 years) were treated with SSCE as an initial intervention for LGIB. A
      definitive bleeding site was identified in 95 per cent of cases (22/23). Eleven
      patients (48%) developed an early complication [recurrent bleeding (n=5; two
      required surgery), asymptomatic ischemic colonic mucosa (n=3), acute renal
      insufficiency (n=1; resolved), and femoral pseudo-aneurysm (n=2; one treated
      operatively)]. Long-term (mean 19 months) follow-up was available for 17
      patients. Five patients (22%) experienced recurrent LGIB, and three patients had
      evidence of colonic ischemic. One patient required endoscopic dilation of a
      stricture, and three underwent surgical resection. There was no mortality in our
      series. In this series, SSCE was an effective first-line therapy for LGIB.
      Rebleeding and ischemia rates were low.

PMID- 16089116
TI  - Two distinct phenotypes of rat vascular smooth muscle cells: growth rate and
      Production of tumor necrosis factor-alpha.
AB  - The monoclonal theory of atherosclerosis postulates that a subpopulation of
      vascular smooth muscle cells (VSMCs) is selectively expanded in response to
      pathologic stimuli and accumulates in vascular intima. The purpose of this
      research was to clone VSMC, determine growth rates of the clones and their
      ability to release the mitogenic cytokine tumor necrosis factor-alpha (TNF
      alpha). With approval of the institutional animal care and use committee, VSMCs
      were isolated and cultured from the thoracic aortas of three rats. To confirm
      that the cells in primary culture were of smooth muscle origin, they were
      immunostained with anti-alpha-smooth muscle-actin antibodies. Single cell-derived
      individual colonies with uniform appearance were surrounded by cloning rings,
      released with trypsin, and expanded. Growth rates of the clones were assessed by
      the mitochondrial dependent reduction of methyltetrazolium (MTT) to formazan
      after 24-hour stimulation with 10 per cent serum. Additionally, cloned cells were
      stimulated with 0.1, 1, 10, and 20 microg/mL lipopolysaccharide (LPS) for 24
      hours, and TNF-alpha was determined in the culture medium. Data were analyzed by
      ANOVA. Two clones were isolated that could be divided into categories based on
      distinctly different morphology: 1) spindle-shaped (SP) or 2) epithelioid-shaped
      (EP) VSMCs. The SP clone had a growth rate that was 25 per cent higher than the
      EP clone (P < 0.05). Also, the SP clone had significantly higher release of TNF
      alpha in response to LPS. For instance, TNF-alpha released in response to 0.1
      microg/mL of LPS in the SP clone was 157 +/- 45 pg/mL versus 21 +/- 8.5 pg/mL in
      the EP clone (P < 0.05). Primary cultures of rat VSMCs are heterogeneous and
      consist of at least two morphologically distinct cell types. These clones are
      different in growth rate and cytokine production. It is possible that selective
      expansion of one of these clones contributes to formation of stenotic vascular
      lesions.

PMID- 16089117
TI  - Effect of the 80-hour work week on cases performed by general surgery residents.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) implemented
      mandatory work week hours restrictions in 2003. Due to the traditionally long
      hours in general surgery, the effect of restrictions on surgical training and
      case numbers was a matter of concern. Data was compiled retrospectively from
      ACGME logs and operating room (OR) records at a university hospital for 2002 and
      2003. Work week restrictions began in January 2003. This data was reviewed to
      determine resident case numbers, both in whole and by postgraduate year (PGY).
      Mean case numbers per resident-month in 2002 were 8.8 +/- 8.2 for PGY1s, 16.2 +/-
      15.7 for PGY2s, 31.4 +/- 12.9 for PGY3s, 31.5 +/- 17.6 for PGY4s, and 31.5 +/-
      17.6 for PGY5s. In 2003, they were 8.8 +/- 5.2 for PGY1s, 16.6 +/- 13.9 for
      PGY2s, 27.8 +/- 12.5 for PGY3s, 38.2 +/- 18.8 for PGY4s, and 26.1 +/- 9.6 for
      PGY5s. PGY1s, PGY2s, PGY3s, PGY4s, or all classes were not statistically
      different. PGY5s did have statistically fewer cases in 2003 (P = 0.03). PGY5s did
      have statistically fewer cases after the work-hours restriction, which likely
      represented shifting of postcall afternoon cases to other residents. Comparing
      other classes and all PGYs, case numbers were not statistically different.
      Operative training experience does not appear to be hindered by the 80-hour work
      week.

PMID- 16089118
TI  - Surgeon-performed ultrasound improves localization of abnormal parathyroid
      glands.
AB  - With a secure diagnosis of hyperparathyroidism, preoperative localization of
      abnormal glands is the initial step toward limited parathyroidectomy (LPX). We
      investigated whether ultrasonography in the hands of the surgeon (SUS) could
      improve the localization of abnormal parathyroids when sestamibi scans (MIBI)
      were negative or equivocal. One hundred eighty patients with sporadic primary
      hyperparathyroidism (SPHPT) underwent preoperative SUS and MIBI scans before LPX
      guided by intraoperative parathormone assay. When the sestamibi scans were
      negative, SUS was used to localize the parathyroid, distinguish parathyroid from
      thyroid tissue, and to guide the intraoperative jugular venous sampling for
      differential elevation of parathyroid hormone (PTH). Operative findings,
      intraoperative hormone dynamics, and postoperative calcium levels determined
      successful localization. MIBI was negative or equivocal in 36/180 (20%) patients:
      (1) showed no parathyroid gland in 22 patients, (2) suggested an incorrect
      location for the abnormal gland in 9, and (3) was insufficient in recognizing
      multiglandular disease in 5. In these 36 patients, the addition of SUS led to the
      successful identification of the abnormal tissue in 19/36 (53%). In the remaining
      17 patients with negative/equivocal scans, the parathyroid could not be clearly
      visualized by SUS. In these patients, SUS facilitated LPX by aiding preoperative
      transcutaneous jugular venous sampling for differentially elevated PTH (n=3) and
      identifying questionable thyroid nodule versus parathyroid tissue (n=1). Overall,
      SUS was useful in 23/36 (67%) patients with nonlocalizing MIBI scans, thus
      improving the rate of localization from 80 per cent to 93 per cent (P < 0.01).
      Surgeon-performed cervical ultrasonography improved the localization of abnormal
      parathyroids by MIBI scan, adding to the success of limited parathyroidectomy.

PMID- 16089119
TI  - 5-year follow-up after sentinel node mapping for breast cancer demonstrates
      better than expected treatment outcomes.
AB  - We conducted this study to provide one of the initial assessments of treatment
      outcomes for breast cancer patients evaluated with sentinel node mapping. All
      patients diagnosed with breast carcinoma, evaluated with sentinel node mapping,
      and followed for 5 years were divided into three groups depending on sentinel
      node(s) status. Group I (node negative) included 91 patients, 77 with invasive
      cancer, and 7 lost to follow-up. Of the remaining 70 patients, 3 (4.3%) suffered
      a distant recurrence and died, 1 developed an in-breast recurrence, and 9 (12.9%)
      developed a contralateral cancer during the study. Group II (IHC positive)
      included 28 patients. One (3.6%) developed a distant recurrence and died of
      breast cancer, and one developed a contralateral cancer during follow. Group III
      (H&E positive) included 36 patients with 1 lost to follow-up. Five patients
      (14.3%) died of breast cancer and two (5.7%) developed contralateral carcinomas
      during follow-up. The most striking observation was a lower than expected rate of
      distant recurrences in these patients followed for 5 years after a diagnosis of
      breast cancer and staging with sentinel node mapping. The ability to identify
      subtle nodal metastasis and design appropriate systemic therapeutic strategies
      may explain this finding.

PMID- 16089120
TI  - Large gastric mesenteric cyst: case report and literature review.
AB  - The case is a 33-year-old white female presenting with a 3-day history of
      abdominal pain. On initial examination, she was found to have significant right
      lower quadrant tenderness. Workup included computed tomography, which
      demonstrated a large cystic mass appearing to be of ovarian origin. The patient
      required an exploratory laparotomy, at which time she was found to have a large
      cyst involving the lesser curvature of her stomach. The cyst was successfully
      resected, and the patient had a rapid postoperative recovery with complete
      resolution of symptoms. Histopathologic evaluation of the specimen identified a
      mesenteric cyst. Mesenteric cysts are uncommon; gastric involvement is
      exceedingly rare. A review of the literature is presented.

PMID- 16089121
TI  - Mesenteric venulitis in a 71-year-old man after acute appendicitis.
AB  - Mesenteric inflammatory veno-occlusive disease (MIVOD) is a clinicopathological
      entity recently described for a case series of patients with intestinal ischemia
      of unknown etiology. MIVOD is characterized as a venulitis with lymphocytic,
      necrotizing, or mixed granulomatous morphology. The disease seems to be self
      limiting with resolution of symptoms after surgical resection. We describe a 71
      year-old man who developed focal intestinal ischemia in the postoperative period
      after laparoscopic appendectomy. At re-exploration, a 20-cm segment of grossly
      ischemic jejunum was identified and resected. The excised specimen demonstrated
      early ischemic mucosal injury and necrotizing mesenteric venulitis with
      thrombosis, consistent with verso-occlusive disease. The etiology of this rare
      vasculitis is currently unknown. We present our case report, which is followed by
      a review of the literature of MIVOD.

PMID- 16089122
TI  - Metastatic thymic carcinoid: a case report.
AB  - Thymic neuroendocrine carcinomas (carcinoid) are rare tumors. They have malignant
      potential, the capacity for distant metastasis, and often present with associated
      endocrinopathies. This report describes a patient who was diagnosed with thymic
      carcinoid and Cushing syndrome at age 19 that, despite complete surgical excision
      of his tumor, developed local recurrence with distant metastases to his brain,
      lungs, and bone. We discuss the evolution of this patient's illness as well as
      the therapies used in his care. Due to the nature of these tumors to recur both
      locally and distant, the importance of aggressive surgical management is
      emphasized. We also discuss the role of adjuvant therapy, which in our case
      consisted of chemotherapy, radiotherapy, and several new therapies including an
      antiangiogenesis agent and a tyrosine kinase inhibitor.

PMID- 16089123
TI  - Coronary artery bypass via resternotomy after pectus excavatum repair.
AB  - Pectus excavatum is a chest wall deformity that commonly warrants pediatric
      surgical correction for cosmesis or respiratory impairment via sternotomy. The
      repair typically consists of sternal wedge osteotomy and subsequent placement of
      a Steinman pin across the sternum with fixation to the ribs bilaterally. Coronary
      artery bypass grafting (CABG) after surgical repair of the sternum with a metal
      implant poses an intriguing surgical challenge. Literature review reveals only
      one such previously described case. We present a case of coronary
      revascularization in an adult who previously underwent pectus excavatum repair
      with ligation of the internal mammary arteries. Our coronary revascularization
      was accessed through a resternotomy after surgical removal of the metal implant
      previously placed during the pectus excavatum repair. Autologous greater
      saphenous vein was used as a conduit for bypass. The patient did well
      postoperatively and was discharged on postoperative day 4. The pectus repair
      remained intact even after the median sternotomy was performed. This was
      confirmed at the 1-year follow-up for the patient. Resternotomy after pectus
      excavatum repair with a prosthetic implant poses a challenge to cardiothoracic
      surgeons. Many such repairs have been described in the pediatric population. As
      our society ages and coronary artery disease becomes more prevalent, this unique
      situation may be more commonly encountered. We present an approach to coronary
      artery bypass grafting via median resternotomy after pectus excavatum repair.

PMID- 16089124
TI  - The effect of storage on the survival of cancer cells in blood and efficient
      elimination of contaminating cancer cells by a leukocyte depletion filter.
AB  - Preoperative autologous blood pooling has been employed in patients with
      malignant tumor. However, it has not been reported how the survival period of
      tumor cells contaminating the preoperative pooled blood changes corresponding to
      the storage period. Intraoperative blood salvage (IBS) is used together with
      preoperative blood pooling. However, IBS in oncologic surgery is generally
      regarded as a contraindication. In the current study, using cytokeratin 19 (CK
      19) mRNA reverse transcription polymerase chain reaction method, we examined the
      survival period of cultured cancer cells in the pooled blood and the efficacy of
      irradiation and leukocyte depletion filter in eliminating cancer cells in the
      blood. Expression of CK-19 mRNA was observed in the pooled blood stored for 21
      days. The number of cancer cells decreased to about 1/10 in the blood stored for
      14 days. We irradiated blood with cancer cells with doses of 25 Gy or 100 Gy. No
      change was observed in the amplified CK-19 signal strength immediately after and
      1 day after irradiation at 100 Gy. After filtration of blood with cancer cells
      through the leukocyte depletion filter, no CK-19 mRNA was detected. Blood
      filtration with the leukocyte depletion filter was effective in eliminating
      cancer cells in the blood.

PMID- 16089125
TI  - Common femoral vein aneurysm simulating an inguinal hernia.
AB  - Common femoral vein aneurysms are rare, yet knowledge of this entity is important
      for the surgeon who performs hernia repairs. This is because common femoral vein
      aneurysms can simulate inguinal or femoral hernias, and misdiagnosis can lead to
      significant morbidity if treated incorrectly. To our knowledge, only five other
      cases of femoral aneurysms simulating inguinal or femoral hernias have been
      reported. We present the case of a 50-year-old male with inguinal pain and
      swelling who was found to have a common femoral vein aneurysm at surgical
      exploration for hernia repair. The etiology, diagnostic strategy, and management
      options for common femoral vein aneurysm are presented and are followed by
      recommendations for operative management. In the case of an unanticipated femoral
      aneurysm found during hernia repair, we recommend termination of the procedure
      followed by elective repair to be performed after appropriate diagnostic testing
      has been completed.

PMID- 16089126
TI  - Recombinant activated factor VII as an adjunct to packing for liver injury with
      hepatic venous disruption.
AB  - Injuries to the juxtahepatic veins represent a small proportion of all liver
      injuries but constitute the most challenging and deadly form of hepatic trauma.
      Recombinant activated factor VII, established as a crucial therapy for enhancing
      hemostasis in hemophiliacs with inhibitors, has also been used to correct
      coagulopathy after traumatic injury. We report two children with hepatic venous
      injury requiring perihepatic packing and recombinant activated factor VII to
      successfully control hemorrhage.

PMID- 16089127
TI  - Components separation technique and laparoscopic approach: a review of two
      evolving strategies for ventral hernia repair.
AB  - When faced with large ventral hernias, surgeons frequently must choose between
      higher incidence of recurrence after primary repair and higher incidence of wound
      complications after repair with mesh. The aim of this study is to compare early
      outcomes between laparoscopic repair (LR) and components separation technique
      (CST), two evolving strategies for the management of large ventral hernias. We
      reviewed 42 consecutive patients who underwent CST and 45 consecutive patients
      who underwent LR of ventral hernia defects of at least 12 cm2. Demographics,
      hernia characteristics, and short-term outcomes were compared between groups.
      Patients in the LR group were younger (53 +/- 2 vs 68 +/- 2 years, P < 0.0001),
      had greater body mass index (34 +/- 2 vs 29 +/- 1 kg/m2, P = 0.02), and had
      larger hernia defects (318 +/- 49 vs 101 +/- 16 cm2, P < 0.0001) than patients in
      the CST group. The LR resulted in shorter length of hospital stay (4.9 +/- 0.9 vs
      9.6 +/- 1.8 days, P < 0.0001), lower incidence of ileus (7% vs 48%, P < 0.0001),
      and lower incidence of wound complications (2% vs 33%, P < 0.001) than the CST.
      Both techniques resulted in similar operative times, transfusion requirements,
      and mortality. Recurrences occurred in 7 per cent of patients at mean follow-up
      of 16 months in the CST group and 0 per cent at mean follow-up of 9 months after
      LR. The LR may have a short-term advantage over the CST in terms of incidence of
      ileus, wound complications, and hospital stay. Because of their unique advantage
      over traditional hernia repairs, both techniques may play a significant role in
      the future treatment of large ventral hernias. Adequate training will be
      essential for the safe and effective implementation of these techniques within
      the surgical community.

PMID- 16089128
TI  - Monetary lessons from litigation involving laparoscopic cholecystectomy.
AB  - Limited information exists on the relationship between adverse events associated
      with laparoscopic cholecystectomy (LC) and subsequent litigation. Out of 104
      suits concerning LC, 18 cases were settled for 628,138 dollars; 48 cases resulted
      in a plaintiff's verdict with the plaintiff receiving 2,891,421 dollars; and 18
      cases resulted in a surgeon's verdict. However, when multiple defendant cases
      were excluded, there was <20,000 dollars difference between a negotiated
      settlement and plaintiff's verdict. Given the minimal monetary differences
      between a settlement and a plaintiff's verdict, when a surgeon is the sole
      defendant in a malpractice case concerning LC, the surgeon should encourage their
      carriers not to settle before trial; as only a trial will exonerate the surgeon.
      However, this encouragement should be tempered when there are "red flags" that
      favor the plaintiff, including multiple defendants (especially a hospital), male
      plaintiffs, bile duct injuries, knowledgeable and well-financed plaintiff's
      attorneys, and certain plaintiff's venues.

PMID- 16089129
TI  - Re: Mesh plug hernia repair complications.

PMID- 16089130
TI  - [Current status and development of monitoring on adverse reaction of traditional
      Chinese medicine in China].
AB  - With the wide usage of traditional Chinese medicine (TCM) and the diversity of
      its dosage-forms, the reports about adverse reaction (ADR) caused by TCM were
      gradually increased. As the cradle of TCM with tremendous manufacturing
      enterprise engaged for this purpose, to establish and perfect the TCM ADR
      monitoring is the problem that TCM industry should face to. In this paper, the
      key point of TCM ADR monitoring was made clear by analysing the current situation
      and the problems presented in TCM ADR monitoring in China, and indicated that the
      nowday developing goals of TCM ADR monitoring are to establish and perfect the
      technologic system for TCM ADR monitoring, strengthen the related basic research
      and enhance international communication and cooperation in this field.

PMID- 16089131
TI  - [Surrogate outcomes, intermediary outcomes and their application in TCM clinical
      efficacy evaluation].
AB  - In this paper, the concepts of surrogate outcomes and intermediary outcomes,
      their correlation with the primary outcome, how to select surrogate outcomes and
      intermediary outcomes and the particular requirements for using surrogate
      outcomes in assessing TCM clinical efficacy were discussed and described. It is
      difficult to evaluate clinical efficacy objectively and thoroughly by means of a
      single surrogate outcome for reason of the global characteristics of TCM,
      therefore, to rationally select such intermediary outcomes as important clinical
      symptoms, combination of several syndromes, patients' subject feeling, patients'
      satisfaction for treatment and quality of life, should be beneficial for
      objectively evaluating the efficacy of TCM intervention approaches.

PMID- 16089132
TI  - [Effect of yisui shengxue granule on gene expression in children with beta
      thalassemia].
AB  - OBJECTIVE: To investigate the mechanism of yisui shengxue granule (YSG) in
      children with betathalassemia. METHODS: The changes of hemoglobin (Hb), red blood
      cells (RBC), reticulocyte (Ret) and fetal hemoglobin (HbF) of 20 children with
      beta-thalassemia were measured before and after treatment. The effect of YSG on
      gene expression in myelo-karyocytes in 3 selected children treated effectively by
      YSG was determined by using DDRT-PCR. RESULTS: The hematologic parameters were
      significantly enhanced and the ferritin gene expression declined after treatment
      respectively, as compared with those before treatment, the difference were
      significant (P < 0.01 or P < 0.05). CONCLUSION: YSG could improve the clinical
      symptoms of children with beta-thalassemia. One of its therapeutic mechanisms may
      be its action in decreasing ferritin gene expression so as to effectively relieve
      the accumulation of iron in body.

PMID- 16089133
TI  - [Study on the relationship among the international scales for quality of life
      evaluation in patients with lung cancer, the East Cooperative Oncology Group
      Status and Lung Cancer Symptoms Lists of TCM].
AB  - OBJECTIVE: To investigate the relationship among international scales for quality
      of life (QOL), physical performance assessment and Lung Cancer Symptoms Lists of
      Traditional Chinese Medicine (LCSL) from the viewpoint of clinical observation.
      METHODS: QOL of 363 patients with lung cancer was estimated with two
      international scales, the European Organization for Research and Treatment of
      Cancer QOL Questionnaire LC-43 (EORTC QLQ-LC43) and the Functional Assessment of
      Cancer Therapy General and Lung (FACT-L). In the same time, scores calculated by
      Karnofsky Performance Status (KPS), East Cooperative Oncology Group Status (ECOG)
      and LCSL were recorded. Correlation and consistency among them were analyzed.
      RESULTS: EORTC QLQ-C43, FACT-L were correlated with KPS, ECOG and LCSL, but the
      correlation coefficient was small. All these indexes were consistent. CONCLUSION:
      QOL should be assessed by QOL questionnaire, not by physical performance indexes,
      although they can be the simply forecast indexes of QOL. There is certain
      consistency between LCSL, QOL and physical performance.

PMID- 16089134
TI  - [Familial pedigree analysis of Shen-yin deficiency syndrome in families with type
      2 diabetes mellitus GU].
AB  - OBJECTIVE: To analyse the familial aggregation and genetic predisposition of Shen
      yin deficiency syndrome (SYDS) in families with diabetes mellitus type 2 (DM2).
      Methods One hundred and forty-one DM2 patients were collected from 32 family
      lines in Nanjin area, in which the probands were differentiated as DM2 with SYDS.
      On them, genetic analysis on the characteristics of SYDS was conducted using
      pedigree analysis, morbidity and heritability of the first-degree relatives of
      the probands were calculated, and the action of familial SYDS factor on the
      genesis of the syndrome was assessed by multiple factors regression analysis.
      Results The morbidity rate of SYDS in the first-degree relatives of the probands
      was 33.71%, and the heritability, calculated by Falconer formula, was 80.6%. The
      fitting result of regression analysis showed that familial factor played an
      important role in SYDS genesis (OR = 5.61, P = 0.001), but DM2 itself is not an
      independent risk factor for it. Conclusion DM2 with SYDS shows the tendency of
      familial aggregation and genetic predisposition, genetic factor is associated
      with the genesis of the syndrome. Pedigree research is a good method for
      exploring the relationship between syndrome and genetic factor.

PMID- 16089135
TI  - [Clinical study on spontaneous improvement after blood flow reconstruction
      interfered by tongxinluo capsule in patients with early stage acute myocardial
      infarction].
AB  - OBJECTIVE: To observe and evaluate the effect of tongxinluo capsule (TXL) on
      recovery of ventricular wall with segmental dyskinesia in patients with early
      stage acute myocardial infarction (AMI). METHODS: One hundred and twelve AMI
      patients after percutaneous coronary intervention (PCI) or fibrinolytic therapy,
      were randomly divided into 2 groups, the control group (CG) treated with
      conventional medicine and the interfered group (IG) treated with conventional
      medicine plus TXL. The changes of ventricular wall motion, left ventricular end
      diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were
      observed at different time points (1-w, 2-w, 1-m, 3-m and 6-m) after PCI by using
      two dimensional echocardiography (2DE). RESULTS: The ventricular dyskinetic
      segment recovery rate at 1-w, 2-w, 1-m and 6-m in IG was 11.9%, 18.1%, 18.8% and
      70.02% respectively, which was significantly higher than the respective rates in
      CG (4.1%, 8.3%, 11.1% and 51.68%, P < 0.01), but the 3-m recovery rate in the two
      groups was insignificantly different. LVEDV increase rate in the two groups at 1
      w was insignificantly different, but it significantly increased at 2-w and 1-m,
      and showed a higher rate in CG (P < 0.05). However, at 3-m and 6-m, it
      significantly decreased in IG but was insignificantly changed in CG. Improvement
      of LVEF was insignificant at 1-w, 2-w and 1-m in both groups, but at 3-m and 6-m,
      LVEF was significantly improved in the interfered group (P < 0.01), but still
      showed no obvious change in the control group. CONCLUSION: Conventional western
      medicine combined with TXL can significantly decrease the infarction area,
      improve left ventricular diastolic function in patients with AMI.

PMID- 16089136
TI  - [Effect of tongjingning granule on primary dysmenorrhea].
AB  - OBJECTIVE: To study the mechanisms of tongjingning granule (TJN) on primary
      dysmenorrhea (PD). METHODS: One hundred and twenty PD patients were treated with
      TJN, and 40 patients treated with aspirin as controls. The levels of serum
      estrogen (E2) and progestin (P) content in the luteal metaphase and anaphase
      (MI/AI) as well as endothelin (ET) and calcitonin gene related peptide (CGRP) in
      the metaphase and menstrual stage before and after treatment in partial patients
      were determined. RESULTS: The therapeutic effect , and the curative markedly
      effective rate and improvement rate of main accompanied symptoms of severe and
      moderate PD patients in the treated group were superior than those in the control
      group (P < 0.01). The level of E2 and ET were significantly decreased, and the
      content of P and CGRP were significantly increased in the treated group after
      treatment respectively (P < 0.01). CONCLUSION: JTN not only can regulate ovarian
      hormone, ET and CGRP, but shows advantages in adjusting spirits and emotions,
      improving homeostasis and consolidating the therapeutic effect.

PMID- 16089137
TI  - [Systematic evaluation on clinical literature related with treatment of
      Parkinson's disease with traditional Chinese medicine].
AB  - OBJECTIVE: To analyze the quality of scientific research design of clinical
      literature related with treatment of Parkinson's disease with traditional Chinese
      medicine, so as to objectively evaluate the therapeutic effect of TCM. METHODS:
      According to principles of evidence-based medicine, clinical epidemiology/design
      measurement evaluation (DME), the "Table of Systematic Evaluation of Quality and
      Information Collection for TCM Clinical Research Literature" were established and
      used to evaluate clinical control trial literature related with treatment of
      Parkinson's disease with TCM published during 1979 to 2000. RESULTS: The method
      of randomization was not described in 66.7% of the literature. Although
      randomized design was declared in 33.3 %, problems or mistakes of randomized
      allocation still existed in them. No record about the state of dropped out or
      absconded cases in follow-up study and without any record of samples screening
      presented in all literature. There were some problems of key links concerning
      samples' homogeneity, outcome indexes selection, conclusion deduction and so on,
      which could also influence the quality and reliability of randomized controlled
      trials. CONCLUSION: Methodological design of clinical research of TCM on
      Parkinson's disease should be strengthened.

PMID- 16089138
TI  - [Effects of fuzheng quxie granule on immune cells and cytokines in populations
      with respiratory viral infection].
AB  - OBJECTIVE: To investigate the effect of fuzheng quxie granule (FQG) on immune
      cells and cytokines in populations with respiratory viral infection. METHODS:
      Fifty-nine patients were randomly divided into 3 groups, that is, 19 patients
      treated with conventional western medicine (WM) plus FQG in the treated group, 19
      patients treated with conventional western medicine alone in the WM group, and 21
      patients treated with FQG alone in the TCM group. The levels of T lymphocyte
      subsets, interleukine-2,4,6,10 (IL-2, IL-4, IL-6, IL-10), tumor necrosis factor
      alpha (TNF-alpha), interferon-gamma (INF-gamma) and Th1/Th2 were determined
      before treatment, and at the end of 1st and 2nd week of treatment respectively.
      RESULTS: Before treatment, levels of TNF-alpha, IL-2, IL-6, IL-10 and INF-gamma
      in all patients were significantly higher than normal range (P < 0.05). After
      being treated for 1 week, the levels of serum TNF-alpha, IL-6, and IL-10 were
      significantly decreased in all groups (P < 0.05), serum IL-2 and INF-gamma
      decreased to the normal level in the WM group, but in the treated and the FQG
      group by the end of the 2nd week, the two indexes still remained at the rather
      higher level (P < 0.05). The ratio of Th1 and Th2 in the treated group and the
      FQG group increased significantly by the end of 2nd week, reached the level
      higher than that in the WM group and that before treatment (P < 0.05). No
      significant difference in, T lymphocytes subsets (CD3+ , CD4+ , CD8+) and
      percentage of B and NK cells before and after treatment was found in all the 3
      groups. CONCLUSION: FQG can positively regulate the immune function of patients
      with respiratory tract viral infection in certain degree.

PMID- 16089139
TI  - [Clinical observation on effect of intra-articular injection of sodium
      hyaluronate accompanied with external application of sanhua ointment for knee
      osteoarthritis].
AB  - OBJECTIVE: To observe clinical efficacy of intra-articular injection of Sodium
      hyaluronate (SH) accompanied with external application of Sanhua ointment (SHO)
      for knee osteoarthritis. METHODS: One hundred and twelve patients with
      osteoarthritis were randomly divided into two groups, Group I was treated with SH
      and Group II was treated with SH plus SHO. The entire condition of knee joint in
      the two groups were compared before and after treatment according to Lysholm's
      function scoring. RESULTS: The functional score in the two groups at the 2nd
      week, 5th week, 3rd month and end of 1st year of the treatment course were
      significantly higher than that before treatment (P < 0.05), and the scores
      continuously increased within the first 3 months of treatment. Comparison of
      scores between the two groups showed that scores in Group II was significantly
      higher than those in Group I at the corresponding period. The total effective
      rate after 1 year treatment in Group lI was higher than that in Group II (81.5%
      vs 96.6%, P < 0.05). In Group II , the initial time of symptom improving was
      earlier and the adverse effect disappeared more quickly than those in Group I
      markedly. CONCLUSION: The efficacy of combined therapy of intra-articular
      injection of SH and SHO for knee osteoarthritis was superior to that of intra
      articular injection of SH only.

PMID- 16089140
TI  - [Clinical observation on effect of shenqi fanghou recipe in preventing and
      treating radiation injury in patients with head and neck tumor].
AB  - OBJECTIVE: To observe the therapeutic effect of shenqi fanghou recipe (SFR) in
      preventing and treating radiation injury in patients with head and neck tumor.
      METHODS: One hundred and forty patients with head and neck tumor, including
      nasopharyngeal carcinoma, carcinoma of tonsil or tongue, were randomly divided
      into 2 groups, 70 patients in the observed group were given modified SFR as
      adjuvant to radiotherapy, while 70 patients in the control group were treated
      with radiotherapy alone. The radiation reactions during radiotherapy and the
      condition of late stage radiation injury radiotherapy in patients in the 2 groups
      were observed. RESULTS: The degree of oropharyngeal mucosa reaction, dryness in
      mouth and radiation dermatitis in cervical region in the observed group was
      milder than those in the control group, and the radiation injury induced late
      stage sequelae, such as the degree of mouth-opening was better and the cervical
      muscular sclerosis was better in the observed group than in the control group,
      showing significant difference (P < 0.01). CONCLUSION: SFR has definite effect in
      preventing and treating radiation reaction and late stage radiation injury in
      patients with head and neck tumor.

PMID- 16089141
TI  - [Effect of shenqi fuzheng injection on pre/post-operational change of
      argyrophilic-nucleolar organizer regions in peripheral T-lymphocyte in patients
      with gastric carcinoma].
AB  - OBJECTIVE: To investigate the pre-post operational change of argyrophilic
      nucleolar organizer regions (Ag-NORs) in peripheral T-lymphocyte of patients with
      gastric carcinoma (GC), and to explore the effect of shenqi fuzheng
      injection(SFI) on it. METHODS: Eighty five patients were divided into two groups
      according to the operation performed was radical or non-radical, and the two
      groups were subdivided into two by additional intravenous dripping of SFI was
      given to them or not. The content of Ag-NORs in peripheral T-lymphocyte in all
      patients before and after operation as well as in 12 healthy subjects was
      determined. RESULTS: Content of Ag-NORs in GC patients was significantly lower
      than that in the healthy subject (P < 0.01), which significantly increased after
      patients underwent radical operation (P < 0. 01 or P < 0.05), especially in those
      treated with SFI (P < 0.01). While in patients underwent non-radical operation
      but not treated with SFI, it showed insignificant change after operation, however
      it did significantly increase in those treated with SFI (P < 0.05). CONCLUSION:
      The immune function of T lymphocyte was low in patients with gastric carcinoma,
      post-operational adjuvant treatment of SFI can significantly improve the cellular
      immunity of patients.

PMID- 16089142
TI  - [Experimental research on effect of human mesenchymal stem cells induced by
      shenqi fuzheng injection in cerebral infarction].
AB  - OBJECTIVE: To investigate the effect of shenqi fuzheng injection (SFI) in
      inducing differentiation of human mesenchymal stem cells (hMSCs) in brain stem
      and its effect on nervous function in model rats of cerebral infarction. METHODS:
      Middle cerebral artery occlusion model rats were made, and hMSCs was injected
      into their brain after being amplified in vitro and incubated with SFI for 0.5 h,
      then the survival, migration and differentiation of hMSCs in brain stem as well
      as the change of nervous function in model rats were observed. RESULTS: The post
      transplantation reject reaction to hMSCs was low, it could survive as long as 6
      weeks or more. No difference in area of infarction was shown before and after
      transplantation. Immunohistochemical staining showed that hMSCs expressed human
      neuron specific enolase (NSE), neurofilament (NF) and glial fibrillary acid
      protein (GFAP). The limb-kinetic function and tactile perception were improved in
      the model rats. CONCLUSION: SFI can induce hMSCs differentiate into neurons in
      vivo, and hMSCs may be the ideal germinal cells for treating cerebral infarction.

PMID- 16089143
TI  - [The neuroprotective effects and its mechanisms of qingkailing injection on
      bacterial meningitis induced by E. coli in rabbits].
AB  - OBJECTIVE: To explore the neuro-protective effect and mechanism of qingkailing
      injection (QKL) against cerebral injury caused by E. coli-meningitis (CM).
      METHODS: The CM model rabbits were treated by ampicillin with QKL as adjuvant.
      The leukocyte count and protein content in cerebral spinal fluid (CSF), the
      contents of water, sodium, potassium and calcium in cerebral tissues were
      measured before, 16 h and 26 h after Bacillus coli injection respectively. The
      expression of matrix metalloproteinase-9 (MMP-9) was determined at the same time.
      RESULTS: Adjunctive treatment with QKL can not only inhibit the increase of
      leukocyte cells, protein content in CSF, and water, sodium, calcium content in
      cerebral tissues, but also the decrease of potassium content revealed during
      simple antibiotic treatment. It also can decrease the expression of MMP-9 in
      cerebral tissues of rabbits with CM. CONCLUSION: As an adjunctive treatment, QKL
      can prevent transient inflammatory reaction and aggravation of brain injury in CM
      induced by simple antibiotic treatment, its mechanisms might relate with calcium
      antagonism and attenuation of MMP-9 expression in brain tissues.

PMID- 16089144
TI  - [Effect of Governer Meridian electro-acupuncture on water channel aquaporin-4 in
      experimental spinal cord injured rats].
AB  - OBJECTIVE: To investigate effects of electro-acupuncture (EA) on Du Meridian on
      the water channel aquaporin-4 (AQP-4) expression and hind limbs function recovery
      in experimental spinal cord injured rats. METHODS: One hundred and fifty SD rats
      were divided into the normal group, the model group and the EA group, with 50
      rats in each group, modified Allen method was used to establish spinal cord
      injury model in the model and EA group. Rats in the EA group was EA on Dazhui and
      Ming men acupoints after modelling successfully. At the 1st, 3rd, 7th, 14th and
      21th day after injury, the hind limbs function of rats was evaluated by BBB
      scales respectively, and the AQP-4 expression in spinal cord tissue was
      determined by immunohistochemistry technique and quantity analysed with image
      analyzer. RESULTS: At the 1st day after spinal cord injury, the AQP-4 expression
      was significantly increased in gray matter and white matter of spinal cord in the
      model group and the EA group, which reached the peak at the 3rd day, but showed
      significant difference between the two groups (P < 0.05), and the difference at
      the 7th, 14th and 21th day became more significant (P < 0.01). CONCLUSION: EA on
      Du Meridian can down-regulate AQP-4 expression after spinal cord injury, inhibit
      spinal cord edema for alleviating secondary spinal cord lesion, so as to protect
      the residual normal spinal cord tissues and promote the rebuilding of nervous
      tissues.

PMID- 16089145
TI  - [Inhibitory effect of emodin on proliferation of human lung adenocarcinoma cells
      in vitro].
AB  - OBJECTIVE: To investigate the anti-tumor mechanisms of emodin on human lung
      adenocarcinoma cell line Anip973 (LACC). METHODS: The influence of emodin of
      different concentration at different time on LACC proliferation were determined
      and compared using MTT colorimeric assay and cell growth curve assay. And the
      cell apoptotic rate was determined by flow cytometry and analyzed with electronic
      microscope. RESULTS: In a certain range, the higher concentration and longer
      acting time of emodin could induce the stronger inhibitory effect on tumor cell
      growth and the higher apoptotic rate. The proliferation inhibitory rate reached
      90% after LACC being treated with emodin 60 micromol/L for 72h. CONCLUSION:
      Emodin can significantly inhibit proliferation of human LACC, showing dose-effect
      and time-effect relationship.

PMID- 16089146
TI  - [Effect of qingfei oral liquid on protein expression of transforming growth
      factor-beta1 and platelet derived growth factor-BB of adenovirus type 3I, 7b
      induced human embryonic lung fibroblast cells].
AB  - OBJECTIVE: To explore the effect of qingfei oral liquid (QOL) contained serum on
      protein expression of transforming growth factor-beta1 (TGF-beta1) and platelet
      derived growth factor-BB (PDGF-BB) of adenovirus type 3I, 7b induced human
      embryonic lung fibroblast cells. METHODS: The cells were divided into 5 groups,
      the normal cells group (NCG), the virus control group (VCG), the blank serum
      group (BSG), the ribavirin group (RVG) and the QOL contained serum group (QSG).
      All the cells except those in the NCG were challenged by adenovirus type 3I, 7b
      and treated with correspondent medicine. The contents of TGF-beta1 and PDGF-BB in
      the supernatant of cell culture were monitored by ELISA and compared among
      groups. RESULTS: Contents of TGF-beta1 and PDGF-BB in VCG were significantly
      higher, while those in QSG were significantly lower than those in VCG (P < 0.01).
      CONCLUSION: Adenovirus infection can increase the protein expression of TGF-beta1
      and PDGF-BB of human embryonic lung fibroblast cells. QOL can decrease the
      protein expression of these cytokines, which maybe one of the mechanisms of its
      antiviral effect.

PMID- 16089147
TI  - [Effect of astragalus injection on left ventricular remodeling and apoptotic gene
      caspase-3 in rats after myocardial infarction].
AB  - OBJECTIVE: To investigate the effect of Astragalus injection (AI) on left
      ventricular remodeling and the expression of apoptotic gene caspase-3 in rats
      after myocardial infarction (MI). METHODS: The MI model was established. The
      experimental animals were divided into 4 groups, Group I (the sham-operated
      group), Group II (the sham-operated plus AI group), Group III (the model group),
      Group IV (the model plus AI group). Animals in the II and IV group were
      intraperitoneally injected with 2 ml AI once a day after operation, while animals
      in the I and III group were treated with normal saline of equal volume. After
      treated for 4 weeks successively, the structural change of left ventricle and the
      level of oxyproline in myocardium were observed, and expression of caspase-3 was
      determined by immunohistochemical method. RESULTS: As compared with Group Ill,
      the ultrastructure of myocardium and indexes of left ventricular remodeling were
      improved, the myocardial content of oxyproline decreased (P < 0.05), the caspase
      3 positive cells reduced and caspase-3 mRNA expression significantly down
      regulated (P < 0.05). CONCLUSION: AI can improve left ventricular remodeling,
      inhibit apoptosis by down-regulate the expression of apoptotic gene caspase-3 in
      rats after MI.

PMID- 16089148
TI  - [Effect of combined therapy of xiaoke shen'an capsule and western medicine in
      diabetic nephropathy].
AB  - OBJECTIVE: To observe the therapeutic effect of xiaoke shen' an capsule on
      diabetic nephropathy. METHODS: Ninety patients with diabetic nephropathy were
      randomly divided into two groups, the patients in the control group (CG) were
      treated with conventional western medicine, and those in the treated group (TG)
      were treated with combined therapy of xiaoke shen'an capsule and conventional
      western medicine. The treatment course of both groups was 8 weeks, and the
      therapeutic effect related indexes were measured before and after treatment.
      RESULTS: The curative rate was 85.0% and 73.3% in CG and TG respectively, it was
      better in TG than that in CG (P < 0.05). Indexes such as fasting blood glucose,
      glycosylated hemoglobin, blood pressure, quantity of 24h urinary protein, urinary
      albumin excretion rate, renal function, blood lipids and hemoreheologic
      parameters were significantly different before and after treatment in TG (P <
      0.05 or P < 0.01). As compared with CG, some of these indexes after treatment
      were superior to those in CG (P < 0.01 or P < 0.05). CONCLUSION: Combined therapy
      of xiaoke shen'an capsule and conventional western medicine has definite
      therapeutic effect on diabetic nephropathy.

PMID- 16089149
TI  - [Effect of angong niuhuang pill as an adjuvant treatment on moderate or severe
      neonatal hypoxic-ischemic Encephalopathy].
AB  - OBJECTIVE: To evaluate the clinical efficacy and safety of angong niuhuang pill
      (ANP) as an adjuvant treatment on moderate or severe neonatal hypoxic-ischemic
      encephalopathy (NHIE). METHODS: Thirty-nine neonates with NHIE in the control
      group were treated with conventional treatment, and 58 in the treated group were
      administered orally ANP additionally, and relative indexes were observed.
      RESULTS: The improvement of aspects such as recovery of consciousness, muscular
      tension, and primitive reflex and disappearance of convulsion, in the treated
      group was better than that in the control group (P < 0.01). CONCLUSION: ANP as an
      adjuvant treatment has a definite effect on NHIE, it can promote the recovery of
      patients, decrease the occurrence of sequelae and with high safety, therefore, is
      a drug feasible for clinical application.

PMID- 16089150
TI  - [The CONSORT statenent: Revised Recommendations For Improving the Quality of
      Reports of Parallel-Group Randomized Trials].

PMID- 16089152
TI  - [Clinical experimentation].

PMID- 16089151
TI  - [Application of biotechnics in the identification of Chinese medicinal herbs and
      the production and cultivation of their excellent species].
AB  - In this paper, application of biotechnics in the identification of traditional
      Chinese medicinal herbs, and the production and cultivation of their excellent
      species was discussed, and the relevant references about usage of biotechnics in
      TCM researches published in recent decade were summarized and analysed. Lots of
      literature showed that biotechnics played important roles in the quality
      identification of Chinese medicinal herbs and the researches on new drugs of TCM.

PMID- 16089153
TI  - Oestrogen-dependence of decidualization in some Myomorph rodents: basic endocrine
      mechanisms and their biological significance.

PMID- 16089154
TI  - [Food packaging materials: health, technical and legal problems].

PMID- 16089155
TI  - [Research on influenza virus inhibitors].

PMID- 16089156
TI  - [Study of some biological characteristics of strains of A2/68 influenza virus].

PMID- 16089157
TI  - [New data on trophic behaviour of Italian Simuliidae].

PMID- 16089158
TI  - [Fate of I131-iodinated insulin in incubated tissues].

PMID- 16089159
TI  - [Isolation of a leptospira strain belonging to the serotype pyrogenes in
      Argentina].

PMID- 16089160
TI  - [Presence of Simulium damnosum Th. (Diptera-Simuliidae) in Yemen].

PMID- 16089161
TI  - Nerve growth factor effect on fatty acids in mouse sympathetic ganglia during
      development.

PMID- 16089162
TI  - [Observations on the developmental cycle of Miyagawanella abortus ovis].

PMID- 16089163
TI  - [On mycophenolic acid production in submerged culture].

PMID- 16089164
TI  - [Strychnine and brucine determination in Strychnos Nux Vomica seeds].

PMID- 16089165
TI  - [Control of the adulteration of pepper samples by electrophoretic analysis of
      protein extracts].

PMID- 16089166
TI  - [Problems raising from the control of biological products employed in medicine.
      Control of sera, vaccines, and biological products in France].

PMID- 16089167
TI  - Complexes of alkali metals?

PMID- 16089168
TI  - Behavioral and clinical pathology changes in koi carp (Cyprinus carpio) subjected
      to anesthesia and surgery with and without intra-operative analgesics.
AB  - Fish surgery is becoming increasingly common in laboratory and clinical settings.
      Behavioral and physiologic consequences of surgical procedures may affect
      experimental results, so these effects should be defined and, if possible,
      ameliorated. We document behavioral and clinical pathology changes in koi carp
      (Cyprinus carpio) undergoing surgery with tricaine methanesulphonate (MS-222)
      anesthesia, with and without intraoperative administration of the opiate
      butorphanol (0.4 mg/kg intramuscularly) or the nonsteroidal antiinflammatory
      analgesic ketoprofen (2 mg/kg intramuscularly). For all fish combined, surgery
      resulted in reduced activity, lower position in the water column, and decreased
      feeding intensity at multiple time points after surgery. The butorphanol-treated
      group was the only one not to experience significant (P < 0.05) alterations from
      presurgical behaviors. Clinical pathology changes at 48 h after anesthesia and
      surgery included decreased hematocrit, total solids, phosphorus, total protein,
      albumin, globulin, potassium, and chloride and increased plasma glucose,
      aspartate aminotransferase, creatine kinase, and bicarbonate. The only clinical
      pathology difference between treatment groups was a lower increase in creatine
      kinase in the ketoprofen-treated group. No adverse effects of butorphanol or
      ketoprofen at these doses were identified. These results suggest a mild
      behavioral sparing effect of butorphanol and reduced muscle damage from the
      antiinflammatory activity of ketoprofen.

PMID- 16089169
TI  - Genetic characterization of Indian-origin and Chinese-origin rhesus macaques
      (Macaca mulatta).
AB  - Genetic differences between Indian-origin and Chinese-origin rhesus macaques are
      as great as those between some primate species and can influence the results of
      experiments in which both are used as animal models for the study of the same
      human diseases. Unfortunately, many breeding facilities do not know with
      certainty the origin of the founders of their rhesus breeding colonies. Here I
      summarize the most definitive of the genetic traits among the microsatellite
      (STR) loci and mitochondrial DNA sequences that my laboratory previously reported
      to characterize Indian-origin and Chinese-origin rhesus macaques and then
      estimate the frequencies of these traits and their reliability as indicators of
      country of origin. The expression of diagnostic traits at two or more of four
      different unlinked loci provides a nearly 100% reliability in distinguishing
      rhesus macaques of Indian and Chinese origin.

PMID- 16089170
TI  - Squamous cell carcinomas of the skin at ear tag sites in aged FVB/N mice.
AB  - We report the development of squamous cell carcinomas (SCCs) of the skin at or
      near the site of ear tags composed of a nickel-copper alloy and used for
      identification during the course of a long-term study of incipient congenic FVB/N
      mice containing the human BCL6 transgene (FVB.Cg-Tg[tetO-BCL6]Bbn Tg[EmicroSR
      tTa]83Bop), their littermate controls, and wild-type FVB/N. Of a total population
      of 160 mice, 14 (8.8%) developed SCCs in the tagged (right) ear after a median
      observation period of 25 months, but none of the animals developed tumors in the
      opposite ear (P = 0.0001). Nine of the fourteen mice with SCCs had to be
      euthanized because they were thought to be in distress from the ear condition,
      but the remaining five died or were euthanized for other reasons related to the
      research study. These animals ranged in age from 331 to 921 days at the time of
      death. Five of the tumors were well-differentiated (grade 1) SCCs; the remainder
      were grade 3 and tended to be deeply invasive neoplasms with undifferentiated
      areas containing a spindle cell component. One of these metastasized to kidney.
      When using the FVB/N mouse strain for long-term studies, it is necessary to
      consider that nearly 9% of the population may develop SCCs at or near ear-tag
      sites that may necessitate early removal of the animal.

PMID- 16089171
TI  - Green fluorescent protein (GFP)-expressing tumor model derived from a spontaneous
      osteosarcoma in a vascular endothelial growth factor (VEGF)-GFP transgenic mouse.
AB  - Vascular endothelial growth factor (VEGF) mediates tumor angiogenesis, growth,
      and metastasis. Murine models of metastatic tumors in which green fluorescent
      protein (GFP) expression is driven by the VEGF promoter can be imaged both
      intravitally and externally and thus offer many possibilities for real-time
      studies of tumor angiogenesis, metastasis, and treatment in vivo. In our defined
      flora animal facility, an 11-month-old female transgenic mouse with a C3H
      background (VEGF(P)-GFP/C3H) developed a spontaneous tumor that expressed GFP
      under the control of VEGF. Necropsy and histopathologic examination revealed an
      osteosarcoma with lung metastases. Fresh tumor fragments were transplanted
      successfully into other VEGF(P)-GFP/C3H transgenic mice. During the first five
      generations, the tumor "take rate" was 100% (25 of 25 animals), with a latent
      period of 8 days and an average tumor volume of 1500 mm3 at 36 days. Transplanted
      tumors have maintained their original histopathologic characteristics and
      metastatic behavior. In addition, the tumor grows in wild-type C3H mice with an
      83% take rate (10 of 12 animals) and as monolayer cells in vitro. GFP was
      expressed strongly in tumor tissue, lung metastatic foci, and cultured tumor
      cells. Real-time growth of tumors grown in dorsal skin chambers in C3H mice could
      be visualized using GFP fluorescence. In addition, GFP fluorescence of metastatic
      lesions in lungs of C3H mice was clearly visible by multiphoton laser scanning
      microscopy. This in vitro and in vivo transplantable and metastatic osteosarcoma
      (Os-P0107) is an attractive model for further study of tumor pathophysiology and
      treatment efficiency affecting VEGF expression.

PMID- 16089172
TI  - Validation of an enzyme-linked immunosorbent assay kit using herpesvirus papio 2
      (HVP2) antigen for detection of herpesvirus simiae (B virus) infection in rhesus
      monkeys.
AB  - Serologic testing for antibody to monkey B virus (BV) in macaque sera is
      problematic due to the biohazardous nature of BV antigens. Herpesvirus papio 2
      (HVP2), a herpesvirus of baboons, is nonpathogenic to humans and is genetically
      and antigenically more closely related to BV than is human herpes simplex virus
      1. This paper describes the results of our in-house laboratory that compared a BV
      antigen-based enzyme-linked immunosorbent assay (ELISA) by commercial testing
      laboratory and an HVP2-based ELISA in our laboratory by using 447 sera from 290
      rhesus monkeys. The HVP2-based ELISA identified as positive 99.11% of the sera
      identified as BV-positive by the BV ELISA. The BV antigen-based ELISA identified
      as positive 98.21% of the sera identified as BV-positive by the HVP2-based ELISA.
      The HVP2 ELISA also identified two BV-negative and six BV-equivocal sera as
      positive. Both ELISAs identified the same 85 negative and three equivocal samples
      as negative and equivocal, respectively. The high degree of correlation (weighted
      kappa coefficient, 0.94) between the two tests indicates that the HVP2 ELISA is a
      sensitive and reliable assay for in-house testing of the BV status of rhesus
      monkeys.

PMID- 16089173
TI  - Circadian temperature rhythm of laboratory swine.
AB  - The circadian temperature rhythm (CTR) profile holds promise for monitoring the
      domestic pig's responses to stress and illness. In the present study we
      quantified the CTR profile of nine growing-finishing swine using a time-series,
      small-group design. Temperature was monitored using a probe implanted in the ear
      for 5 1/2 to 9 1/2 consecutive days while the unrestrained pigs were housed
      singly in pens. The dominant period of the temperature data was estimated with
      the autocorrelation function and then used in standard cosinor analysis to
      compute the amplitude (half of the distance between the highest and lowest value
      within the period), mesor (rhythm-adjusted mean), and acrophase (timing of the
      cosine maximum). To examine the effect of procedural stress on CTR, we compared
      data from the first 3 days with those from subsequent days. Eight of the nine
      (89%) pigs had CTR with a mean (+/- standard error) period of 23.6 (0.5) h,
      amplitude of 0.18 (0.02) degrees C, mesor of 38.7 (0.24) degrees C, and acrophase
      at 19:44 h. Mean mesor and acrophase were not different, but amplitude was lower
      (P = 0.03) during the first 3 days after instrumentation than during subsequent
      days. We conclude that: 1) laboratory-housed, unrestrained, growing-finishing
      swine have CTR; 2) our ear-based instrumentation protocol imposes acute stress as
      reflected in attenuated CTR amplitude during the first 3 days after
      instrumentation; and 3) CTR adaptation to stress appears to occur over time.

PMID- 16089174
TI  - Evaluation of two combinations of Domitor, Zoletil 100, and Euthatal to obtain
      long-term nonrecovery anesthesia in Sprague-Dawley rats.
AB  - We sought to evaluate a new protocol designed to maintain long-term, nonrecovery,
      surgical anesthesia in Sprague-Dawley rats. In the first phase, two groups of
      rats were anesthetized with two different dose combinations of Domitor
      (medetomidine) and Zoletil 100 (tiletamine-zolazepam) to investigate their
      efficacy in induction of anesthesia. One combination comprised Domitor at 35
      microg/kg and Zoletil 100 at 40 mg/kg, whereas the other comprised Domitor at 50
      microg/kg and Zoletil 100 at 20 mg/kg. Both combinations effectively induced deep
      anesthesia and caused no mortality, but the duration of anesthesia differed
      statistically. In the second phase, we induced anesthesia with both Domitor
      Zoletil 100 dose combinations then investigated the possibility of maintaining
      anesthesia for 5 h by administering Euthatal (pentobarbitone) intra-arterially at
      10 mg/kg hourly. Depth of anesthesia, mortality, physiological parameters, blood
      gas analysis, hematology, clinical chemistry, and postmortem histopathology were
      recorded. Euthatal provided stable long-term anesthesia with both dose
      combinations of Domitor-Zoletil 100. Seven of 8 (88%) animals anesthetized with
      Domitor at 50 microg/kg and Zoletil 100 at 20 mg/kg successfully were maintained
      under deep anesthesia for 5 h. Higher mortality (36% versus 12%) occurred in
      group of animals treated with Domitor at 35 microg/kg and Zoletil 100 at 40
      mg/kg. This difference may be linked to dose-related respiratory depression, as
      alterations of arterial gas levels were noted. Our findings suggest that, when
      long-term nonrecovery anesthesia is required, doses of 50 microg/kg Domitor and
      20 mg/kg Zoletil 100 are preferable when given with Euthatal to maintain
      physiological conditions in animals.

PMID- 16089175
TI  - Eradication of enteric helicobacters in Mongolian gerbils is complicated by the
      occurrence of Clostridium difficile enterotoxemia.
AB  - Outbred Mongolian gerbils from a United States commercial source were examined
      for colonization with naturally occurring enterohepatic Helicobacter spp.
      Helicobacter spp. were identified in the cecum and colon by culture and by using
      genus-specific primers in polymerase chain reaction (PCR) assays. Nutritionally
      balanced triple-antibiotic wafers (containing amoxicillin, metronidazole, and
      bismuth) used previously to eliminate helicobacter infections in mice were
      administered in an attempt to eradicate the naturally occurring novel
      helicobacters in the gerbils. After 7 days of antibiotic treatment, two of the
      experimental animals died due to Clostridium difficile-associated enterotoxemia.
      However, at 3 weeks after antibiotic cessation, the surviving three animals had
      no Helicobacter spp. in the cecum or colon according to PCR analysis. Eradication
      of Helicobacter spp. using dietary administration of antibiotics was complicated
      by the presence of toxin-producing C. difficile. An alternate method to develop
      helicobacter-free gerbils (such as Caesarian rederivation) may be necessary.

PMID- 16089176
TI  - Relationship of feline bispectral index to multiples of isoflurane minimum
      alveolar concentration.
AB  - The study reported here was done to determine the relationship between bispectral
      index (BIS) values and minimum alveolar concentration (MAC) multiples of
      isoflurane in cats. Isoflurane MAC was determined using the tail-clamp method in
      eight domestic cats. Ten days later, the cats were anesthetized a second time
      with isoflurane at each of five MAC multiples administered in random order.
      Ventilation was controlled and, after a 20-min equilibration period at each MAC
      multiple of isoflurane, BIS data were collected for 5 min and the median BIS
      value calculated. Data from each isoflurane MAC multiple were compared using
      analysis of variance for repeated measures, and statistical significance was set
      at P < 0.05. The MAC of isoflurane (mean +/- 1 standard deviation) was 1.8% +/-
      0.2%. BIS values at 0.5 MAC could not be recorded due to spontaneous movement in
      all eight cats. BIS values at 2.0 MAC were confounded by burst suppression in
      seven of the eight cats. Over the range of 0.8 to 1.5 MAC, BIS values decreased
      significantly with increasing end-tidal isoflurane concentrations. Mean (+/- 1
      standard deviation) BIS measurements were 32 +/- 3 at 0.8 MAC, 20 +/- 4 at 1.0
      MAC, and 5 +/- 3 at 1.5 MAC. Therefore, BIS values are inversely and linearly
      related to end-tidal isoflurane concentrations in anesthetized cats. However, the
      consistently low BIS values recorded in this study suggest that clinical BIS
      endpoints used to titrate anesthetic agents in humans may not be applicable to
      cats.

PMID- 16089177
TI  - Euthanasia of neonatal mice with carbon dioxide.
AB  - Exposure to carbon dioxide (CO2) is the most prevalent method used to euthanize
      rodents in biomedical research. The purpose of this study was to determine the
      time of CO2 exposure required to euthanize neonatal mice (0 to 10 days old).
      Multiple groups of mice were exposed to 100% CO2 for time periods between 5 and
      60 min. Mice were placed in room air for 10 or 20 min after CO2 exposure, to
      allow for the chance of recovery. If mice recovered at one time point, a longer
      exposure was examined. Inbred and outbred mice were compared. Results of the
      study indicated that time to death varied with the age of the animals and could
      be as long as 50 min on the day of birth and differed between inbred and outbred
      mice. Institutions euthanizing neonatal mice with CO2 may wish to adjust their
      CO2 exposure time periods according to the age of the mice and their genetic
      background.

PMID- 16089178
TI  - Use of low-dose chlorpromazine in conjunction with environmental enrichment to
      eliminate self-injurious behavior in a rhesus macaque (Macaca mulatta).
AB  - A 7-year-old, captive-bred, female rhesus macaque was placed in a quarantine
      facility upon arrival at our institution. At release from quarantine, she was
      observed pawing at and chewing on her left cheek. Physical examination revealed
      ulcerative lesions on the buccal surface of the left cheek. Initial differential
      diagnoses included Cercopithecine herpesvirus 1 (B virus)-induced lesions and
      bacterial infection. Dental abnormalities and cheek pouch foreign body were ruled
      out during the physical exam. Treatment with 30 mg/kg cefazolin intramuscularly
      every 12 h was initiated. Twelve days later, the animal presented with a 2 x 2
      cm, full-thickness erosion involving the opposite (right) cheek. Treatment with
      buprenorphine (0.1 mg/kg intramuscularly every 24 h) was initiated. Cultures for
      B virus were negative, and only nonpathogenic bacteria were isolated from swabs
      of the lesions. Hematology and serum chemistry profiles were normal. A wedge
      biopsy of the lesion revealed no definitive etiology. Further observation
      revealed that the lesions likely resulted from self-injurious behavior (SIB).
      Treatment with low-dose chlorpromazine (1 mg/kg intramuscularly once daily for 25
      days, and then 0.5 mg/kg intramuscularly once daily for 25 days) was initiated.
      Bodyweight and condition were maintained during therapy, and serial hematology
      and serum chemistry profiles were normal. The animal was moved into a different
      room, and a toy "necklace" was created. The SIB was eliminated, and lesions
      healed within 35 days. Presently, 20 months after presentation, this animal
      remains in good health.

PMID- 16089179
TI  - Long-term trends in home advantage in professional team sports in North America
      and England (1876-2003).
AB  - Home advantage is quantitatively defined and calculated for each season since the
      start of the main professional sports in North America and England. Over 400,000
      games are analysed. The leagues represented are the National League (1876-2002)
      and American League (1901-2002) for baseball, the National Hockey League (1917
      2003) for ice hockey, the National Football League (1933-2002) for American
      football, the National Basketball Association (1946-2003) for basketball, and the
      four levels of professional football, formerly called the Football League, in
      England (1888-2003). Problems caused by unbalanced playing schedules are
      considered. The results are presented graphically to show long-term trends and
      sudden changes. The highest levels of home advantage for all sports were in their
      early years of existence. Home advantage in ice hockey, basketball and football
      in England has declined over the last two decades. In baseball there has been
      very little change over the last 100 years, with home advantage consistently
      lower than in other sports. There was a large drop in home advantage in football
      in England following the 7-year suspension of the league during the Second World
      War. The trends and changes provide some evidence that travel and familiarity
      contribute to home advantage, but little in support of crowd effects.

PMID- 16089180
TI  - Disconnects between popular discourse and home advantage research: what can fans
      and media tell us about the home advantage phenomenon?
AB  - Many of the factors identified as influencing the home advantage have an
      underlying social basis, presumably through the influence exerted by the home
      crowd. Beliefs in the home advantage and the causes of that advantage also have a
      social basis: sports coverage and fan discourse focus on some aspects of the
      phenomenon at the expense of others. This paper compares home advantage research
      with the use of the concept in media narratives and fan Intemet postings. While
      there are many similarities across sources, the findings suggest three major
      differences. Fans, and to a lesser extent the media, (1) focus almost exclusively
      on winning as the evidence for a home advantage, (2) see crowd noise as the main
      factor for the home advantage, and (3) treat the phenomenon as much more
      transient than is suggested by academic studies. I identify several features of
      the phenomenon that facilitate popular views of the home advantage and suggest
      how future research may benefit from incorporating those views.

PMID- 16089181
TI  - Football supporters' perceptions of their role in the home advantage.
AB  - Football fans' views on their role in the home advantage were obtained by placing
      links to an internet questionnaire on supporters' websites. Altogether, 461 fans
      from clubs which had been promoted, relegated or unchanged in the past season of
      the English football leagues rated crowd support as significantly more
      influential than familiarity, travel, territoriality and referee bias in
      contributing to the home advantage. Fans felt responsible for inspiring their
      team to victory, took credit for distracting opponents, and believed that they
      could influence officials into making decisions in their team's favour. However,
      they did not accept personal blame for poor results. No effects for gender, age
      or the team's outcome in the promotion/relegation battle emerged, though season
      ticket holders were more extreme in their feelings of responsibility overall.
      Furthermore, it was suggested that mechanisms such as the perception of being
      superior to rivals can encourage fans to retain their allegiance to their teams,
      even when outcomes are disappointing. Indeed, affiliation may become so
      incorporated into self-identity that supporters may not have the option of
      abandoning their team, but instead perceive a reciprocal relationship in which
      both they and the team are expected to do their best to achieve success.

PMID- 16089182
TI  - Home advantage in the Australian Football League.
AB  - The results of this study on home advantage in Australian rules football
      demonstrate that individual clubs have different home advantages. Traditional
      measures of home advantage as applied to whole competitions such as percentage of
      games won, and alternative measures such as average margin of victory for the
      home team, are calculated. Problems with these measures are discussed. Individual
      home advantages for each team are obtained using a linear model fitted to
      individual match margins; the resultant home advantages are analysed, and
      variations and possible causes or groupings of home advantage are proposed. It is
      shown that some models allowing different home advantages for different clubs are
      a significant improvement over previous models assuming a common home advantage.
      The results show a strong isolation effect, with non-Victorian teams having large
      home advantages, and lend support to the conclusion that crowd effects and ground
      familiarity are a major determinant of home advantage.

PMID- 16089183
TI  - Game location and aggression in rugby league.
AB  - The present study examined the relationship between aggression and game location
      in rugby league. We videotaped a random sample of 21 professional rugby league
      games played in the 2000 Super League season. Trained observers recorded the
      frequency of aggressive behaviours. Consistent with previous research, which used
      territoriality theories as a basis for prediction, we hypothesized that the home
      team would behave more aggressively than the away team. The results showed no
      significant difference in the frequency of aggressive behaviours exhibited by the
      home and away teams. However, the away teams engaged in substantially more
      aggressive behaviours in games they lost compared with games they won. No
      significant differences in the pattern of aggressive behaviours for home and away
      teams emerged as a function of game time (i.e. first or second half) or game
      situation (i.e. when teams were winning, losing or drawing). The findings suggest
      that while home and away teams do not display different levels of aggression, the
      cost of behaving aggressively (in terms of game outcome) may be greater for the
      away team.

PMID- 16089184
TI  - The home advantage in sport competitions: Courneya and Carron's (1992) conceptual
      framework a decade later.
AB  - This paper had three aims. The first was to review research carried out on the
      home advantage from 1992 to the present. The second was to examine the extent to
      which a conceptual framework proposed by Courneya and Carron (1992) was/is viable
      as a tool to highlight and organize an understanding of the home advantage. The
      final aim was to provide suggestions for future research.

PMID- 16089185
TI  - Do judges enhance home advantage in European championship boxing?
AB  - There have been many examples of contentious points decisions in boxing.
      Professional boxing is scored subjectively by judges and referees scoring each
      round of the contest. We assessed whether the probability of a home win (and
      therefore home advantage) increased when bouts were decided by points decisions
      rather than knockouts. Overall, we found that bouts ending in points decisions
      had a significantly higher proportion of home wins than those decided by a
      knockout, though this effect varied across time, and controlling for relative
      quality of boxers was only effective when using more recent data. Focusing on
      these data, again the probability of a home win was higher with a points decision
      and this effect was consistent as "relative quality" varied. For equally matched
      boxers ("relative quality" = 0), expected probability of a home win was 0.57 for
      knockouts, 0.66 for technical knockouts and 0.74 for points decisions. The
      results of the present study lend general support to the notion that home
      advantage is more prevalent in sports that involve subjective decision-making. We
      suggest that interventions should be designed to inform judges to counter home
      advantage effects.

PMID- 16089186
TI  - Home advantage in speed skating: evidence from individual data.
AB  - Home advantage is a well-documented phenomenon in many sports. Home advantage has
      been shown to exist for team sports (soccer, hockey, football, baseball,
      basketball) and for countries organizing sports tournaments like the Olympics and
      World Cup Soccer. There is also some evidence for home advantage in some
      individual sports, but there is a much more limited literature. This paper
      addresses the issue of home advantage in speed skating. From a methodological
      point of view, it is difficult to identify home advantage, because skaters vary
      in their abilities and the conditions of tournaments vary. There is a small but
      significant home advantage using a generalized linear mixed model, with random
      effects for skaters and fixed effects for skating rinks and seasons. Even though
      the home advantage effect exists, it is very small when compared to variation in
      skating times due to differences of rinks and individual abilities.

PMID- 16089187
TI  - Audience support and choking under pressure: a home disadvantage?
AB  - This paper highlights the not-so-obvious but compelling reasons why the same
      supportive audiences that can help performers attain their highest potential also
      may increase performers' risk of choking under pressure. Drawing primarily from
      social psychology research and theory, we conclude that audience support
      magnifies performance pressure and induces performers to avoid failure rather
      than seek success during the most critical moments of performance contests.
      Although supportive audiences can inspire performers to excel when motivation
      would otherwise be lacking, audiences may also lead performers towards
      maladaptive self-monitoring and overcautiousness when the stakes are highest. The
      increased self-focus that supportive audiences induce can disrupt the automatic
      execution of the skills performers possess. Dispositional and situational
      moderators of the relationship between audience support and performance are
      reviewed.

PMID- 16089188
TI  - Home advantage and the debate about competitive balance in professional sports
      leagues.
AB  - A recurrent theme in sports economics is the extent to which overall league
      attendances will be raised by measures, such as revenue sharing, which aim to
      improve competitive balance. This debate has ignored the phenomenon of home
      advantage, which may, however, be important to the extent that, if all teams had
      equal talent, all matches may then be weighted heavily in favour of the home
      team. We present an analysis of the relationship between attendance and match
      level uncertainty in the English Football League. A simulation from our model
      indicates that equality of playing talent would in fact lower aggregate
      attendance. This result is explained by the loss of prospectively the most
      uncertain games, where weak teams have home advantage over strong teams.

PMID- 16089189
TI  - Two hours at work, with Amanda.

PMID- 16089190
TI  - Variations on the concept of traumatism: traumatism, traumatic, trauma.
AB  - In this paper, the author outlines Freud's fundamental hypotheses concerning the
      concept of traumatism, then goes on to differentiate three notions (French being
      a particularly apposite language for such a venture): 'traumatism', 'traumatic'
      (in a substantive sense) and 'trauma'. These three terms correspond to the three
      turning points in Freud's theory with respect to the concept of traumatism (1895
      97, 1920, 1938). The author evokes also the developments that are due to
      Ferenczi, particularly in his later writings (1928-33), where he defined and
      discussed the question of 'trauma' in contemporary clinical practice; the author
      goes on to explore the different variations on this theme as regards mental
      functioning. He then defines, from a metapsychological point of view, the
      differences between 'traumatisms' that have been 'worked over by secondary
      processes', organised and governed by the pleasure-unpleasure principle
      ('traumatism') and 'early' or 'primary traumatisms', which interfere with the
      process of binding the instinctual drives ('trauma'); states of mind influenced
      by a traumatic imprint ('traumatic') are looked upon as belonging to both
      categories of the above mentioned traumatisms. The author illustrates his
      hypotheses with a clinical example.

PMID- 16089191
TI  - The basic traumatic situation in the analytical relationship.
AB  - The author attempts to develop a concept of psychic trauma which would comply
      with the nucleus of this Freudian notion, that is, an excess of excitations that
      cannot be processed by the mental apparatus, but which would also consider the
      functions and the crucial role of objects in the constitution of the psychism and
      in traumatic conditions, as well as taking into account the methodological
      positioning according to which the analytical relationship is the sole possible
      locus of observation, inference and intervention by the psychoanalyst. He
      considers as a basic or minimal traumatic psychoanalytical situation that in
      which a magnitude or quality of emotions exceeds the capacity for containment of
      the psychoanalytical pair, to the point of generating a period or area of
      dementalisation in the psyche of one or both of the participants, of requiring
      analytical work on the matter and promoting a significant positive or negative
      change in the relationship. Availing himself of Bion's theory about the alpha
      function and the metapsychological conceptions of Freud and Green concerning
      psychic representations, he presents two theoretical formulations relating to
      this traumatic situation, utilising them according to the 'altered focus' model
      proposed by Bion. He presents three clinical examples to illustrate the concept
      and the relevant theoretical formulations.

PMID- 16089192
TI  - Los Degradados: out, down, dead. Transmitted and inflicted trauma as encountered
      in the analysis of a 6-year-old girl.
AB  - The author presents the analysis of a precocious traumatized little girl, which
      reveals the ways in which historical trauma is transmitted and intrafamilial
      trauma is both disguised and represented. The play as it evolves is seen to
      simultaneously communicate what the child struggles with and to resolutely try to
      hide what has actually happened. Analyst and child together participate in play
      which utilizes displacement, enactment and interactive enactment, the latter play
      mode being the very hallmark of profound traumatic experience. Carlotta, the
      child, helps the analyst to follow her quest for meaning making even as the
      interaction between them adheres to and departs from the deepening pentimenti of
      traumatic experience, which needs to be unraveled and reconstructed in order that
      her own developmental progression can be rejoined. The analysis facilitates
      Carlotta's capacity to play in a more unfettered fashion and to assist her
      family's recovery as well.

PMID- 16089193
TI  - The specificity of torture as trauma: the human wilderness when words fail.
AB  - The author attempts to situate the specificity of torture--understood as the
      product of political violence and of totalitarian states--within the historical
      framework of the concept of trauma in psychoanalysis. When the mind and social
      ties are simultaneously affected, the intrapsychic and transpersonal aspects of
      the suffered damage intertwine in a complex and unique web. The author aims to
      dismantle the notion of victim, considering it both stigmatizing and inaccurate.
      The goal is not just to identify the after-effects and the disabilities suffered
      by those affected by torture, but also to integrate their experiences and their
      narratives into a life project. Rather than individual psychopathology, this
      essay reflects upon those phenomena of suggestion and hypnosis that are at work
      in human groups under ordinary conditions and that are exacerbated under social
      crises, following the Freudian axis developed in Group psychology and the
      analysis of the ego.

PMID- 16089194
TI  - Psychodynamic assessment of changes in children with autism under psychoanalytic
      treatment.
AB  - In this article the authors report insights into autism developed through their
      extensive experience of psychoanalytic therapy with children with autism. The
      first stages of body psychic development are seriously disrupted by this
      pathology, resulting in primitive anxieties of falling and of being liquefied.
      These anxieties are connected to the fragile development of body ego and of its
      related spatiotemporal organisation. The changes in children observed by the
      authors during the therapeutic process lead them to offer a psychodynamic
      assessment tool, which revolves principally around the development of body ego.
      After the initial state of 'severe autism', the authors describe three stages:
      the stage of 'recovery of the skin' (Bick); the established 'symbiotic phase',
      subdivided into 'vertical then horizontal splitting of the body ego'; and finally
      the stage of 'individuation'. First, the authors describe the principal
      psychoanalytic approaches to autism and reflect on the links possible with non
      psychoanalytic work.

PMID- 16089195
TI  - Destruction and guilt: splitting and reintegration in the analysis of a
      traumatised patient.
AB  - The author traces in detail how, in the analytic relationship, she was slowly
      able to read aspects of the trauma as 'quotations' and gradually, through
      transference, transform them into a symbolic language. Split-off aggression and
      guilt feelings became progressively accessible to interpretation through
      transferential projective identifications. During his analysis, the patient
      discovered he was the child of Nazi criminals: on his mother's side they were the
      third generation; on his father's side, the second.

PMID- 16089196
TI  - Confidentiality with respect to third parties: a psychoanalytic view.
AB  - It is assumed that confidentiality is not one singular ethical entity but a
      conglomerate of quite different issues depending upon clinical context and the
      sector of information sharing at stake. The focus here is on how to think
      psychoanalytically about requests for information from third parties (payers,
      courts, public security). Defining confidentiality as a promise to 'never tell
      anything' outside of the relationship omits evaluation of the impact of the
      third's listening on the combined freedom of thought and freedom of speech in
      analyst and analysand. Circulation of information outside the dyad need not be
      toxic, need not disrupt the analytic couple's openness to new meaning. Key to
      contamination and inhibition of analytic work is whether or not disclosure serves
      an analytic end. Current defense of confidentiality relies heavily on the models
      of protection of privacy and professional secrecy, which, though useful and
      relevant, fail to encompass the transitional, intersubjective space engendered by
      the analytic process. Suggestions are made for alternate sources of paradigms
      better suited to represent the latter. Offered for discussion is a draft of a
      confidentiality policy with respect to third parties that is informed by
      psychoanalytic theory and clinical practice rather than by local legal
      jurisdiction or original disciplines' ethics codes.

PMID- 16089197
TI  - Leonardo's phantasy and the importance of Freud's slip. The role of the analyst's
      phantasies in applied psychoanalysis and in the analytic relation.
AB  - In his paper on Leonardo, Freud made a slip. Referring to the bird which,
      according to one of Leonardo's memories, tossed its tail into the painter's mouth
      many times when he was a child, Freud replaced 'kite' with 'vulture'. It is
      widely accepted that this slip doesn't significantly damage the whole of Freud's
      constructions on the paper, nevertheless, the part of his considerations relating
      to the meaning of 'vulture' should be discounted. In the author's view, this part
      of the Leonardo paper is necessary. Thanks to the slip Freud was able to reach a
      comprehension which otherwise would have been unattainable. Interpretation based
      on the vulture made possible the configuration of a mother as 'daughter of the
      wind' as was the case not only with Leonardo's mother but also with Freuds.
      Interpretation of Leonardo's phantasy was achieved through Freud's unconscious
      identification with Leonardo and the slip adequately interpreted becomes the
      evidence of this. Through identification, Freud succeeded in making sense of
      Leonardo's memory but also in realising an indirect virile possession of his own
      'winged' mother Freud's position as interpreting subject in his paper on Leonardo
      also has more general value: the analyst's knowledge about the 'other' has a very
      important basis in the indirect expression of his unconscious wishes within the
      field of sense. The author uses clinical material in order to show how the
      analyst's phantasies play an important role in analytical interpretive work.

PMID- 16089198
TI  - A disturbance of interpreting, of symbolisation and of curiosity in the analyst
      analysand relationship (the patient without insight).
AB  - The author examines the function of the analyst who may distort the unconscious
      communication with the patient by means of the expression of his
      countertransference. He studies a disturbance in curiosity and in symbolisation
      in a patient with a narcissistic pathology. Both problems were related to this
      failure in interpreting. The curiosity of the patient, which initially seemed to
      be non-existent, was found to be directed towards investigating the mind of the
      analyst, this being his sole purpose. The disturbance in symbolisation was
      manifested as a constant verbal acting out, which was expressed as verbal
      communication empty of meaning. A change in the interpretative attitude enabled a
      modification in the objective of the curiosity, which became focused on
      investigating his own inner world, and the emptiness of the verbal communication
      was replaced by representations. This change in communication allowed the analyst
      to relate the facts of the psychoanalytic relationship both with the patient's
      phantasy and with the events in his history. An idealised identification with
      destructive aspects of the mother towards the father was discovered. This
      idealisation had been sustained by the analyst by means of his errors in
      interpreting. The author explores disturbances in symbol formation and in the use
      of symbols, and he considers the different states of emptiness.

PMID- 16089199
TI  - The Gottingen study of psychoanalytic therapy: first results.
AB  - Results of a naturalistic study of the effectiveness of psychoanalytic therapy
      are reported. Outcome data are presented for a sample of N = 36 patients who were
      treated with psychoanalytic therapy. For a sample of n = 23 of these patients,
      data for 1-year follow-up are available at present. According to the results,
      psychoanalytic therapy yielded significant improvements in symptoms (Symptom
      Checklist 90-R, SCL-90-R and rating of psychoanalysts), in interpersonal problems
      (Inventory of Interpersonal Problems, IIP), in quality of life (Questionnaire of
      Quality of Life, FLZ), in well-being (Questionnaire of Changes in Experience and
      Behaviour VEV) and in target problems defined by the patients (Goal Attainment
      Scaling, GAS). Large effect sizes between 1.28 and 2.48 were found in symptoms
      (GSI of the SCL-90-R), interpersonal problems (IIP-total), quality of life (FLZ
      total), well-being (VEV) and target problems (GAS). At 1-year follow-up, all
      improvements proved to be stable or even increased. The self-reported
      improvements in symptoms were corroborated by the ratings of the psychoanalysts.
      At the end of therapy, 77% of the patients showed clinically significant
      improvements. In the 1-year follow-up group, this was true for 80%. Further
      results are presented and discussed.

PMID- 16089200
TI  - In the shadow of a controversy: Freud and Ferenczi 1925-33.
AB  - In recent literature, Freud's relation with pioneers of psychoanalysis has been
      reevaluated. This paper describes the evolution of the relation between Freud and
      Ferenczi during their most controversial period--1925-33. The consequences of
      this evolution on psychoanalytic theory and practice are shown. The links between
      events of the protagonists' lives, their reflections about them, and the
      resulting theoretical elaboration (e.g. on homosexuality, female sexuality,
      problems of separation) are also taken into account. This work is essentially
      based on their recently published correspondence.

PMID- 16089201
TI  - Analytical space and work in Russia: some remarks on past and present.
AB  - In this paper, the author outlines the historical-cultural picture in the former
      USSR and post-Soviet Russia. He looks at some facets of psychoanalysis in Russia
      in the years immediately before and after the October Revolution as well as in
      its recent history, exploring the implicit question of how the wider social
      context, and specifically totalitarian and post-totalitarian reality, has
      influenced psychoanalytic work and analytic space in this country. With the help
      of Sebek's concept of the totalitarian object and Britton's formulations about
      the triangular space, the author attempts to understand the interaction of
      external and internal space and to give an introduction to the problem of
      establishing the analytic setting as well as finding some new possibilities of
      enlarging the space for new psychoanalysts in Russia.

PMID- 16089202
TI  - Submission, inhibition and sexuality: masochistic character and psychic change in
      Austen's Mansfield Park.
AB  - Mansfield Park is Austen's most controversial novel. 'Squarely taking on such
      issues as class, gender, sexuality, religion, education, theatricality, and
      colonialism, Mansfield Park now appears to occupy a more critical place in
      Austen's canon and in literary and cultural history generally than that perennial
      favorite, Pride and prejudice' (Johnson, 1998, p. xiii). Austen's heroine, Fanny
      Price has generated heated controversy because of the provocative contradictions
      in her character which this paper argues tally with the psychoanalytic
      understanding of moral masochism within the masochistic character As a child
      neglected at home and then sent to a frightening new environment, in which she
      was lowest and last, Fanny Price needed the love and protection even of those who
      mistreated her. She needed to control and influence them with submission and the
      inhibition of her aggressive impulses and through a vigilant scrupulousness.
      Austen created a plot in which she also dramatized the seeds of change that lie
      within the submissive character, within the repressed and inhibited psychosexual
      desire linked to the father which can drive the reemergence of wishes for love
      and satisfaction in situations of relative safety.

PMID- 16089203
TI  - Psychoanalytical teamwork in a day hospital: revisiting some preconditions for
      patients' subjective appropriation.
AB  - Psychoanalytical 'teamwork' may be recommended for dealing with a particular kind
      of transference that characteristically occurs during the institutional treatment
      of young patients presenting psychotic or behavioural symptoms. In such cases,
      the degree of alienation is such that repetition is usually induced in other
      people (the therapists), filling in for fantasy construction that seems to be
      lacking in the patient's psyche. A case like that of 'Angel' can give some idea
      of this phenomenon, wherein several caregivers have to harbour fragmented and
      incompatible elements of the case's particular history, which are in need of more
      mental representation. Any subjective restitution and appropriation of these
      elements by the patient would require a sort of detour (often a trying one!) by
      way of the psychical space of caregivers whose initial task will be to 'work it
      through' among themselves.

PMID- 16089204
TI  - Intergenerational transmission of psychopathology.

PMID- 16089205
TI  - Psychoanalysis and the academic world.

PMID- 16089206
TI  - Adolescent psychoanalysis: how we work--clinical models in practice. Two clinical
      cases with detailed session material.

PMID- 16089207
TI  - An update on time.

PMID- 16089208
TI  - Freud and Jung today: Oedipus and symbolisation.

PMID- 16089209
TI  - Artist and model: psychoanalytic perspectives.

PMID- 16089210
TI  - Developing psychoanalysis under socio-political pressure: viewpoints from Eastern
      Europe.

PMID- 16089211
TI  - On: incorporation of an invasive object.

PMID- 16089212
TI  - On: incorporation of an invasive object.

PMID- 16089213
TI  - On: what can we learn from psychoanalysis and prospective studies about
      chemically dependent patients?

PMID- 16089214
TI  - On: a boycott by passport.

PMID- 16089215
TI  - On: projective identification and consciousness alteration.

PMID- 16089216
TI  - On the threshold of the creative imagination: Swimming pool (2003).

PMID- 16089217
TI  - Inflammatory chronic otitis media and the anterior epitympanic recess.
AB  - OBJECTIVE: To demonstrate the important role of the anterior epitympanic recess
      (AER) in the surgery of noncholesteatomateous chronic inflammatory middle ear
      disorders. To establish selective criteria as to the indication of surgical
      intervention on the AER, aiming to create a permanent anterior aeration pathway
      for the attic. In addition, to point out the mandatory role of preoperative
      temporal bone computed tomography (CT) demonstrating whether the AER is involved
      and thus contributing, within the clinical context, to the indication for this
      surgery and its appropriate approach. STUDY DESIGN: Prospective study on patients
      with persistent or recurring chronic inflammatory middle ear disease for at least
      3 years, after failure of conventional medical or surgical treatments. SETTING:
      Tertiary referral university centre. PATIENTS: Between November 2002 and July
      2003, every patient presenting with clinical findings suggestive of an AER
      pathology was included in this study. SURGERY: Surgical approach of the AER
      during a mastoatticotomy and tympanoplasty with excision of the Cog and the
      tensor tympani fold, preserving the ossicular chain in almost all cases. OUTCOME
      MEASURES: Absence of postoperative otorrhea, satisfactory otoscopic examination,
      and improvement in the air-bone gap postoperatively in case the presurgery
      hearing level was abnormal and not due to an ossicular chain abnormality.
      RESULTS: Eight patients were included in the study. The preoperative CT scan
      showed AER opacities in all patients that were either isolated or associated with
      a diseased meso- or hypotympanum or the mastoid cavity. The measurement of the
      relevant transverse diameter of the AER is proposed to evaluate preoperatively
      the distance between the Cog laterally and the facial nerve canal medially to
      minimize the risk of a perioperative injury. During the operation, we found
      granulation tissue and adhesions in the AER in all cases A clinical follow-up 3
      months after the intervention showed good local control in all patients, absence
      of otorrhea, and almost complete closure of the air-bone gap at audiometric
      evaluation. The last clinical follow-up in August 2004, a mean of 18 months after
      our intervention, did not reveal any relapse of symptoms in any case. CT control
      could be obtained in five of eight cases, within 13 to 21 months after the
      intervention, showing a reaerated tympanic cavity and AER. CONCLUSION: The AER
      plays a major role in sustaining some noncholesteatomateous chronic or recurrent
      inflammatory middle ear disorders that do not respond to conventional medical
      treatment. Definitive control of this pathology will be obtained by approaching
      the AER through an excision of the Cog and the tensor tympani fold, exenterating
      the inflammatory tissues, and creating a sufficient and permanent anterior
      atticomesotympanic communication. The indication for such a surgical approach is
      highly dependent on clinical findings correlated to temporal bone CT. Familiarity
      with the AER and its critical role should become part of every resident's
      training program in otology.

PMID- 16089218
TI  - Perioperative mortality in oncologic head and neck surgery.
AB  - OBJECTIVE: The aim of this study was to establish the causes of perioperative
      mortality after head and neck oncologic surgery, to improve operative strategies
      and surgery procedures, and to reduce postoperative complications. SETTING:
      University Hospitals of Strasbourg, Head and Neck Department. PATIENTS AND
      METHODS: The medical files of patients who died within 30 days of presentation
      with epidermoid carcinoma of the head or neck were analyzed; criteria included
      age, sex, medical history, and the location and stage of development of the
      tumour. MEASUREMENT METHOD: The causes of death are discussed with reference to
      the pre- and postmortem observations. RESULTS: In this study, the perioperative
      mortality rate was 3.07%. It depended more on tumour stage and the medical
      history of the patient than on tumour location and the age of the patient. The
      responsibility of the medical team itself was involved in some cases. DISCUSSION
      AND CONCLUSION: The study shows the difficulty of establishing the cause of death
      of weakened patients who have undergone a heavy surgical operation. Although the
      majority of deaths recorded are considered to have been unavoidable, for a small
      number of them, the absence of vital function monitoring over the first days
      after the operation was a contributory cause. Perioperative mortality has greatly
      decreased over the last 30 years and is, at present, almost nonexistent during
      anesthesia in head and neck surgery.

PMID- 16089219
TI  - Early identification of rhinocerebral mucormycosis.
AB  - OBJECTIVES: Mucormycosis is an acute and often fatal infection caused by a fungus
      of the Mucorales order of the Zygomycetes class. In the majority of cases, it is
      associated with an underlying disorder, such as diabetes mellitus with
      ketoacidosis, or with immunocompromising factors, but it may appear in healthy
      people, although rarely. Early diagnosis and treatment are critical to prevent an
      otherwise fatal outcome. This article presents and discusses the early (alarming)
      signs and symptoms and the predisposing factors that should be considered to
      avoid delays in diagnosis. METHODS: We review seven cases of rhinocerebral
      mucormycosis admitted to our hospitals from 1998 to 2003. RESULTS: All patients
      had an underlying immunocompromising factor and/or diabetes mellitus. Five
      patients had palatal necrotic ulcers and/or black eschars. Three patients had
      unilateral blindness, and two patients required orbital exenteration. Four
      patients died because of a delayed diagnosis. CONCLUSIONS: Early diagnosis is
      critical in the prevention of intracranial extension of the infection, which is
      the cause of death in 80% of cases. Therefore, a high index of clinical suspicion
      is essential in immunocompromised or diabetic patients with acute sinus
      infection. Identification of a fungal organism on histopathology is the most
      specific element for diagnosis. A team approach to management is recommended for
      early surgical debridement, correction of diabetic ketoacidosis, and systemic
      antifungal agents. Timely medical-surgical treatment proves extremely important
      for prognosis.

PMID- 16089220
TI  - Emotional effects of nasal packing measured by the Hospital Anxiety and
      Depression Scale in patients following nasal surgery.
AB  - The aim of this study was to test the validity of the Hospital Anxiety and
      Depression (HAD) Scale in patients who underwent nasal surgery as a method of
      screening for emotional disorders during their hospital stay. The study group
      consisted of 50 adult patients (29 male, 21 female) who underwent nasal surgery
      for different reasons, such as chronic sinusitis, nasal polyposis, and nasal
      septal deviation. Functional endoscopic sinus surgery and/or septoplasty were
      managed in these patients, and all of the patients had nasal packing applied
      bilaterally for 2 days. The HAD Scale was given to all of the patients 1 day
      before surgery and 1 day after surgery, with anterior nasal packing bilaterally
      during the hospital stay. The anxiety and depression levels of the male group
      were under the cutoff points. For the female group, the depression levels were
      under the cutoff points, and the anxiety levels were high in the preoperative
      period and decreased after the operation. Anxiety and depression levels in the
      pre- and postoperative periods for the male and female groups were analyzed by
      Paired t-test. No statistically significant result was found (p > .05). It was
      concluded that, for patients well informed about nasal packing and hospital
      conditions, nasal packing may be used safely, without any psychological
      disturbance. The HAD Scale should be a more useful screening method to diagnose
      emotional disorders, especially in patients who are hospitalized for a long time.

PMID- 16089221
TI  - Hydrogen peroxide mouth rinse: an analgesic post-tonsillectomy.
AB  - OBJECTIVE: To compare the analgesic efficacy of hydrogen peroxide (H2O2) mouth
      rinse with control for post-tonsillectomy pain management. DESIGN: Double
      blinded, prospective, randomized, controlled clinical trial. PATIENTS AND
      METHODS: Thirty-seven patients from 5 to 14 years old undergoing electrocautery
      tonsillectomy were randomized to either the H2O2 mouth rinse or the water rinse
      (control) group. For 14 days, patients recorded pain levels twice daily using a
      visual analogue scale. Analgesic uses, as well as any complications, were also
      noted by the patients. RESULTS: Thirty-seven patients completed the study, 21 in
      the treatment group and 16 in the control group. Mean postoperative days of pain
      were 10.3 and 8.3, respectively, and differed significantly (p = .008). Mean
      postoperative days of analgesic use were 9.0 and 6.7, respectively, and differed
      significantly (p = .005). Only one incidence of postoperative hemorrhage occurred
      in the study group. CONCLUSION: In our study, the H2O2 mouth rinse does not
      provide a better analgesic effect than the water rinse for post-tonsillectomy
      pain relief.

PMID- 16089222
TI  - Sinonasal endoscopy reporting format: emphasis on chronic rhinosinusitis.
AB  - The role of nasal endoscopy has been well characterized in terms of diagnosis and
      treatment, the methods of performing the endoscopy, and the findings that can be
      visualized within the nasal cavities. The reporting format of such findings has
      not been the subject of such detailed popularity. A structured format would
      create a common language between otolaryngologists, potentially facilitating
      outcomes assessment and/or research by providing an objective tool for recording
      findings. More so, professional associations might use a structured format for
      government or billing negotiations and justifications. The following sinonasal
      endoscopy reporting format represents a synthesis of clinical experience from
      three rhinologists in attempting to document endoscopic findings in the nose and
      sinuses. Our primary objective was limited to establishing a standardized format
      that will be suitable for objective outcomes assessment and communication between
      endoscopic sinus surgeons. It is also hoped that this reporting format can be
      correlated with patients' subjective quality of life outcomes.

PMID- 16089223
TI  - Partial inferior turbinectomy using the microdebrider.
AB  - BACKGROUND: A microdebrider was selected to accomplish partial inferior
      turbinectomy, allowing for controlled and rapid removal of hypertrophic soft
      tissue while preserving the general turbinate form. OBJECTIVE: To assess the
      clinical outcome, healing, and any adverse consequences from the microdebrider
      partial turbinectomy procedure. SETTING: A public hospital in north-central
      Israel. DESIGN: A nonrandomized prospective study of 35 adults who were referred
      for nasal airway surgery, including turbinectomy. METHODS: All patients underwent
      bilateral inferior turbinate reduction with the microdebrider, with removal of
      mucosa from the medial and inferior portions of the inferior turbinates. Detailed
      follow-up was accomplished at 4 or more months postoperatively, including a
      visual analogue scale questionnaire and videoendoscopy. For seven patients, pre-
      and postoperative mucosal biopsies were available to evaluate healing and
      epithelial regeneration. RESULTS: Nasal endoscopy showed well-healed turbinate
      membranes and preservation of the turbinate form, with widening of the
      inferomedial nasal airway space. Subjective nasal patency improved after surgery,
      p < .01, and the subjective sense of smell was improved, p < .01, without
      associated crusting, pain, irritation, sneezing, or dryness. Postoperative
      biopsies showed subepithelial fibrosis and regenerated epithelium, generally of
      respiratory differentiation. CONCLUSION: Inferior turbinate reduction can be
      accomplished efficiently with the microdebrider device, without undue side
      effects. SIGNIFICANCE: Further experience and long-term follow-up with this
      technique are warranted.

PMID- 16089224
TI  - Lobular capillary hemangioma of the nasal cavity.

PMID- 16089225
TI  - Second branchial cleft cysts with mediastinal extension: the diagnostic
      challenge.

PMID- 16089226
TI  - Parotid magnetic resonance imaging, sialography, and parotid biopsy for diagnosis
      of Sjogren's syndrome in a patient with negative serology.

PMID- 16089227
TI  - Laryngeal manifestation of autoimmune disease: rheumatoid arthritis mimicking a
      cartilaginous neoplasm.

PMID- 16089228
TI  - Polypoid degeneration of the middle turbinate mucocele mimicking intranasal
      neoplasia.

PMID- 16089229
TI  - Penetrating esophageal foreign body: metallic wire in the thyroid gland.

PMID- 16089230
TI  - Basaloid squamous carcinoma of the larynx and hypopharynx: immunohistopathologic
      features of two cases.

PMID- 16089231
TI  - Malignant fibrous histiocytoma of the thyroid gland: recurrence treated by
      radiotherapy.

PMID- 16089232
TI  - Esophageal foreign body in a prison inmate: genuine suicide attempt or pursuit of
      illness for secondary gain?

PMID- 16089233
TI  - Resistant microorganisms in head and neck infections.
AB  - The key pathogens most commonly associated with acute infections in the upper
      respiratory tract include Streptococcus pneumoniae, Haemophilus influenzae,
      Moraxella catarrhalis and Streptococcus pyogenes. Antimicrobial resistance
      amongst these organisms to many of the commonly used agents for treatment
      continues to evolve. S. pneumoniae is probably the most important pathogen in the
      respiratory tract and antimicrobial resistance of this organism to many drugs
      appears to be rising. For some organisms, such as S. pyogenes, resistance to
      standard therapy such penicillin has not been described. For others, such as M.
      catarrhalis, beta-lactamase production has become the norm, with over 90% of
      isolates now producing this enzyme. One of the major drivers of resistance
      continues to be the overuse and misuse of antibiotics in the community. This is
      complicated by the fact that most therapy is empiric and the exact etiology of a
      patient's infection is not known. Despite the fact that the clinical impact of
      antibiotic resistance on patient outcomes is not always clear, it remains prudent
      to consider the issue of resistance when selecting therapy for a patient and to
      continue to strive for appropriate antibiotic use as a means to stem the tide of
      evolving resistance.

PMID- 16089234
TI  - Infectious adult rhinosinusitis: etiology, diagnosis, and management principles.
AB  - Rhinosinusitis represents a complicated and multifaceted group of diseases that
      is generally classified into the categories of acute and chronic. Although many
      instances of acute rhinosinusitis lasting longer than 7 days are thought to be of
      bacterial origin, most are thought to be inflammatory rather than infectious. The
      contribution of infectious organisms to the pathogenesis of chronic
      rhinosinusitis is an area of controversy and active investigation. Examples of
      these areas of investigation include biofilms, osteitis, and bacterial
      superantigens. This review discusses the role of infectious organisms in both
      acute and chronic sinusitis, with special focus on the etiology and diagnosis of
      these conditions, and includes a discussion of principles of their management.

PMID- 16089235
TI  - Pediatric sinusitis: update.
AB  - Sinusitis in children is a very common condition. It is being seen more and more
      by primary care physicians and pediatricians. Children average six to eight colds
      per year. Of those, 0.5 to 5% will develop a sinus infection. Symptoms of a cold
      or allergy overlap with those of rhinosinusitis in the child. Distinguishing
      rhinosinusitis from a cold or allergy may be challenging. It is agreed that if
      cold symptoms are not improving by 7 to 10 days, a sinus infection should be
      seriously considered. Plain radiographs can be helpful for maxillary sinusitis
      especially if an air-fluid level is seen; otherwise, the sensitivity and
      specificity of plain radiographs are poor. Computed tomography (CT) should not be
      used for diagnostic purposes. The role of CTis mainly in children with chronic
      rhinosinusitis when surgery is being considered. In cases of complicated
      sinusitis, a CT scan is necessary. Treatment of most rhinosinusitis cases in
      children is medical. Antibiotics constitute the mainstay of medical treatment.
      Medical treatment should be with an appropriate antibiotic and for at least 14
      days. Adjunctive treatment with saline irrigations and topical and systemic
      decongestants may be helpful. Surgical intervention is necessary for complicated
      cases and for cases that do not respond to prolonged course of medical
      management. Currently adenoidectomy and endoscopic sinus surgery are the most
      common procedures used. Children needing surgical intervention are a small
      percentage because of the success of medical treatment. When and which surgical
      procedure to use are discussed in detail.

PMID- 16089236
TI  - Fungal rhinosinusitis: state-of-the-art diagnosis and treatment.
AB  - The past 30 years has been witness to a period of tremendous growth and
      innovation within the field of rhinology, facilitating a better understanding and
      improved management techniques for a variety of local and systemic conditions
      manifesting within the nose and paranasal sinuses. Of these disease states, the
      spectrum of conditions considered under the rubric of fungal rhinosinusitis best
      exemplifies modern rhinology's position as a truly multidisciplinary specialty.
      We review the classification of the various forms of fungal rhinosinusitis and
      their clinical presentations, radiologic findings, and treatment options.

PMID- 16089237
TI  - Otitis media and the new guidelines.
AB  - Otitis media, including recurrent acute otitis media (AOM) and otitis media with
      effusion (OME), is one of the most common reasons for an illness-related visit to
      the primary care clinician. Until recently, antibacterial therapy was the
      standard treatment for most episodes of AOM and often for OME. However, in 1994,
      a clinical practice guideline on OME was developed by the Agency for Healthcare
      Policy and Research (now the Agency for Healthcare Research and Quality) and
      applied to normal children aged 1 to 3 years. The recommendations in the 1994
      guideline were evidence based, widely discussed, and somewhat controversial but
      also acted as a starting point for some ideas about standardization of management
      of this very common disease. In 2004, revised clinical practice guidelines were
      published for OME that applied to children aged 2 months to 12 years and included
      children with developmental disabilities and underlying conditions that
      predispose them to OME. In addition, a new evidence-based clinical practice
      guideline for AOM was published in 2004. This guideline recognized that many
      episodes of AOM will resolve on their own without antimicrobial therapy, and on
      that basis, one of the recommendations for initial treatment of AOM in specified
      situations was watchful waiting without antibacterial therapy. This article
      briefly discusses the current knowledge about AOM and OME and then addresses the
      new AOM and OME guidelines point by point. It is important to remember that
      although important, these clinical practice guidelines are just guidelines and
      that actual management of the patient with otitis media depends on clinical
      judgement, the severity of the illness, other underlying medical conditions,
      ready access to adequate follow-up care, and other features, such as cultural
      differences. Surgical recommendations were not included in the AOM guidelines but
      were addressed in the OME guidelines. Further information about the efficacy and
      effectiveness of both sets of guidelines will likely include the results of
      prospective studies using the guidelines in both normal children and those with
      underlying medical conditions.

PMID- 16089238
TI  - Complications of otitis media: an evolving state.
AB  - The advent of antibiotics in the 1930s and 1940s has led to a decline in the
      incidence of otitis media complications. However, otitis media and its
      complications are continuing to evolve owing to the emergence of antibiotic
      resistance and the introduction of pneumococcal vaccines. Modern high-resolution
      computed tomographic scans have allowed for earlier diagnosis when signs and
      symptoms are present, but a high index of suspicion must be maintained because
      the clinical presentation may be quite subtle. The intent of this article is to
      discuss the intracranial and extracranial complications of acute and chronic
      otitis media. The clinical presentation, work-up, and management of the
      individual complications are presented.

PMID- 16089239
TI  - Nontuberculous mycobacteria in children: a changing pattern.
AB  - Nontuberculous mycobacteria (NTM) infections seem to be increasing in numbers and
      in severity in developed countries worldwide. OBJECTIVE: To document the severity
      and to assess whether an increase in cases has occurred over the years, we
      described the epidemiology, clinical presentation, investigations, and treatment
      of NTM adenitis seen at the Montreal Children's Hospital. METHODS: Cases were
      identified through revision of the microbiology laboratory database for positive
      NTM culture from any site and through retrieval by the medical records of charts
      of patients with a diagnosis of adenitis and a node biopsy or excision or a
      diagnostic code of NTM disease, between 1990 and 2004. These charts were reviewed
      retrospectively. RESULTS: Over the 15-year period, we identified 36 patients with
      a median age of 2.8 years with NTM adenitis. Of these cases, 22 (61%) occurred in
      the past 5 years. Only 3 children were born outside Canada. The majority (92%)
      presented with a cervicofacial mass, and 25% had constitutional symptoms or
      fever. There were 3 cases of mediastinal adenitis and 2 cases of cervical disease
      extending to the deep neck vessels, all of which occurred in the past 5 years.
      The purified protein derivative (PPD) test for tuberculosis was positive (> or =
      10 mm) in 11 of 15 patients tested (73%), none of whom had ever had contact with
      tuberculosis. Thirty-three patients had surgery. Of the 26 patients who had
      excisional biopsy or functional neck dissection, 15% required a second surgery
      for persistence or recurrence compared with 100% of those who had incision and
      drainage or curettage. Cultures were positive in 72% of the 32 specimens sent,
      mainly for Mycobacterium avium complex. Very few complications were noted.
      CONCLUSION: The number of cases of NTM disease has almost doubled between 2000
      2004 compared with between 1990-1999, with more invasive cases seen in the past 4
      years. The significance of this important rise in numbers is still unclear.
      Resolution of NTM adenitis is higher with complete surgical excision of affected
      lymph nodes. Moreover, given the proportion of PPD > or = 10mm among those
      tested, a pan-Canadian study assessing the incidence of NTM disease compared with
      tuberculosis is required to determine if a change in the recommendations for PPD
      positivity is needed.

PMID- 16089240
TI  - Tonsillopharyngitis: clinical highlights.
AB  - Tonsillopharyngitis is an extremely common infection seen in adults and children.
      Although the symptoms and signs of this disease are usually sufficient to make a
      diagnosis, it is often difficult to make a distinction between bacterial and
      viral etiology on clinical grounds alone. The complications of
      tonsillopharyngitis may be classified into suppurative and nonsuppurative
      complications. The nonsuppurative complications include scarlet fever, acute
      rheumatic fever, and post-streptococcal glomerulonephritis. Suppurative
      complications include peritonsillar, parapharyngeal, and retropharyngeal
      cellulites and/or abscess. Features suggestive of viral bacterial (GABHS)
      etiologies, the medical and surgical guidelines for managing tonsillopharyngitis,
      and its complications are highlighted in this article.

PMID- 16089241
TI  - Is donepezil therapy associated with reduced mortality in nursing home residents
      with dementia?
AB  - BACKGROUND: Since cholinesterase inhibitors (CEIs) were approved for use in mild
      to moderate Alzheimer's disease, the therapeutic efficacy of this class of
      medications has largely centered on demonstration of short-term improvement in
      cognition and global function. Later evidence suggested that the beneficial
      effects of CEIs might be sustainable for at least 3 years and that CEIs may have
      a disease-modifying effect on Alzheimer's disease. These broad-ranging, long-term
      effects may explain the recent finding that the use of a CEI among nursing home
      residents with dementia was associated with lower mortality. OBJECTIVE: The goal
      of this study was to investigate whether donepezil treatment is associated with
      reduced mortality in nursing home residents who have dementia. METHODS: We
      performed a retrospective matched cohort study using the Systematic Assessment of
      Geriatric Drug Use via Epidemiology database, which contains data collected with
      the Minimum Data Set on a cross section of 915,469 nursing home residents aged >
      65 years between 1998 and 2000 in 6 US states. We identified users of donepezil
      (5 and 10 mg) and an equal number of matched nonusers in the same facility, date
      of donepezil use, level of cognitive function, and dementia diagnosis.
      Comparisons of the 2 groups were made for sociodemographic variables, dementia
      severity, number of medications, and major comorbid illnesses (heart disease,
      cancer, diabetes mellitus, chronic obstructive pulmonary disease, and
      malnutrition), as well as survival over the 2-year study period. RESULTS: A total
      of 5423 users and 5423 nonusers of donepezil were identified. Based on Cox
      proportional hazards models, donepezil users showed a lower mortality rate than
      nonusers. The hazard rate ratio was 0.89 (95% CI, 0.83-0.95). After adjusting for
      the confounding variables, sociodemographic factors, other psychotropic drugs,
      and comorbid conditions, this survival advantage remained (hazard rate ratio,
      0.90; 95% CI, 0.84-0.96). CONCLUSIONS: A relationship was observed between
      treatment of nursing home residents with donepezil and lower mortality. If the
      relationship was due to a direct effect of donepezil use, then this observation
      has implications for the socioeconomic impact of CEI therapy in those with
      advanced dementia in the nursing home. These implications deserve future
      investigation.

PMID- 16089242
TI  - Open-label, observational study of the effects of risperidone on the behavioral
      and psychological symptoms of dementia and caregiver stress in the community
      setting.
AB  - BACKGROUND: Behavioral disturbances and psychological symptoms of dementia--such
      as agitation, aggression, and psychosis--compromise patients' quality of life and
      daily functioning as well as contribute to caregiver burden and the decision to
      institutionalize the relative with the disease. OBJECTIVE: The goal of this study
      was to examine the effects of risperidone on noncognitive symptoms and caregiver
      burden in the community setting. The tolerability of risperidone was also
      assessed. METHODS: This was an observational, open-label, multicenter study.
      Dementia patients with behavioral and psychological symptoms received risperidone
      for 3 months. At 1 and 3 months, physicians rated symptoms on the
      Neuropsychiatric Inventory (NPI) and the Clinical Global Impression of Severity
      (CGI-S) scale. Caregivers rated their distress in relation to individual NPI
      items using the NPI Caregiver Distress (NPI-D) scale. Outcome variables were
      analyzed using Friedman and Wilcoxon tests. RESULTS: A total of 263 patients
      (mean age, 77.5 years) received a mean (SD) risperidone dose of 1.4 (0.7) mg/d at
      1 month and 1.5 (0.8) mg/d at 3 months. The total NPI score (mean [SEM])
      decreased from 33.7 (1.91) at baseline to 11.9 (0.98) at month 3 (P < 0.01), and
      the NPI-D score decreased from 22.5 (1.02) at baseline to 9.0 (0.64) at month 3
      (P < 0.01). Agitation/aggression and sleep disturbances were the most improved
      symptoms and caused the largest decrease in caregiver burden. Improvements were
      also noted on the CGI-S scale (from 4.0 at baseline to 3.4 at month 3; P < 0.01).
      Extrapyramidal symptoms decreased significantly (P < 0.05) over the course of the
      study. CONCLUSIONS: In this study of community-based patients with dementia,
      risperidone significantly improved behavioral and psychological symptoms and, as
      a result, also reduced caregiver burden. Risperidone was well tolerated in this
      elderly population, particularly with regard to extrapyramidal symptoms.

PMID- 16089243
TI  - Dextromethorphan-induced delirium and possible methadone interaction.
AB  - INTRODUCTION: Dextromethorphan is a commonly used antitussive agent that can be
      purchased over the counter. It is metabolized primarily by the cytochrome P450
      (CYP) 2D6 isozyme. Methadone has been found to inhibit CYP2D6, indicating a
      potential for interaction with dextromethorphan. CASE SUMMARY: An 83-year-old
      woman was evaluated for delirium, hypersomnia, confusion, lethargy, impaired
      concentration, and poor food intake. Symptoms resolved soon after discontinuing
      dextromethorphan. DISCUSSION: Vulnerability to delirium was potentially caused by
      coadministration of methadone, which can inhibit the CYP2D6 isozyme. CONCLUSION:
      Evaluation of delirium should include close investigation of the patient's
      medications for potential interactions with dextromethorphan.

PMID- 16089244
TI  - Olanzapine-induced vasculitis.
AB  - INTRODUCTION: Elderly patients are particularly vulnerable to adverse drug
      reactions as a result of polypharmacy and metabolic changes associated with
      aging. We present a case of leukocytoclastic vasculitis induced by olanzapine, a
      medication commonly used in elderly patients. CASE SUMMARY: An 82-year-old woman
      was admitted to the extended-care center for short-term rehabilitation after
      prolonged hospitalization for a pulmonary embolism requiring mechanical
      ventilation. The pulmonary problem resolved, but her hospitalization and
      subsequent rehabilitation were complicated by agitated delirium, which was
      treated with olanzapine and modification of contributory factors. At the time of
      admission to the rehabilitation facility, the patient had been receiving warfarin
      for 2 weeks and olanzapine for 6 days. On the eighth day after initiation of
      olanzapine, erythematous skin lesions developed on dependent areas. The
      international normalized ratio for warfarin was within the acceptable range;
      however, because warfarin has been associated with subcutaneous bleeding
      presenting as petechiae and ecchymosis, subcutaneous enoxaparin was substituted
      for warfarin. The skin lesions continued to worsen over the next week and
      developed into palpable lesions. Biopsy of the rash revealed leukocytoclastic
      vasculitis. In the absence of another cause, olanzapine was discontinued and the
      rash improved significantly. When the agitation recurred, risperidone was
      initiated, but the patient experienced dizziness with this agent. Olanzapine was
      resumed and the skin lesions recurred. Olanzapine was then changed to quetiapine,
      and the skin lesions improved over the next few weeks. DISCUSSION: Olanzapine is
      commonly used in elderly patients to control behavioral disturbances associated
      with dementia, delirium, and other psychiatric disorders. Leukocytoclastic
      vasculitis is an infrequently reported adverse drug reaction with olanzapine. Its
      exact pathogenic mechanism is unknown, but both cell-mediated and humoral
      immunity appear to play important roles. Because drug-induced vasculitis has an
      identical clinical presentation and identical serologic/pathologic parameters to
      idiopathic forms of vasculitis, a high index of suspicion is necessary for its
      accurate diagnosis. CONCLUSIONS: Because adverse drug reactions are common in
      elderly patients taking multiple medications, physicians should be vigilant when
      starting new medications and should attempt to eliminate unnecessary medications.
      Clinicians should be aware of the potential for leukocytoclastic vasculitis in
      association with olanzapine.

PMID- 16089245
TI  - Duloxetine for management of stress urinary incontinence.
AB  - OBJECTIVE: The aim of this article was to review data regarding the efficacy and
      tolerability of duloxetine, a selective serotonin (5-HT)-norepinephrine (NE)
      reuptake inhibitor that has received US Food and Drug Administration marketing
      approval for the treatment of major depressive disorder and painful diabetic
      neuropathy, and that has been investigated as a treatment for stress urinary
      incontinence. METHODS: A MEDLINE/PubMed search was conducted to identify English
      language study reports. In addition, proceedings of meetings of the International
      Continence Society, European Association of Urology, American Urological
      Association, and American College of Obstetrics and Gynecology were reviewed for
      relevant abstracts (search terms included duloxetine, thiophenes, serotonin
      uptake inhibitors, adrenergic uptake inhibitors, and stress urinary
      incontinence). Additional references were obtained from the bibliographies of
      these sources. Data for the period from 1986 through January 2005 were reviewed.
      RESULTS: All in vitro and in vivo studies of duloxetine were included. Because
      both 5-HT and NE are involved in the maintenance of urinary continence,
      duloxetine may have a role in the treatment of urinary incontinence. Duloxetine
      is primarily eliminated via metabolism, with < 1% of the parent compound excreted
      via urine. Duloxetine QD or BID has been found to be significantly superior to
      placebo in reducing incontinence episode frequency (P < 0.001 to P < 0.05),
      increasing the interval between micturitions (P < 0.001 to P = 0.004), and
      improving the condition as measured by patient self-report (P < 0.001 to P =
      0.028) and incontinence quality-of-life scores (P = 0.002 to P = 0.03). The most
      problematic adverse events are nausea, dry mouth, constipation, dizziness, and
      insomnia. CONCLUSIONS: Although statistically superior to placebo in efficacy
      trials, the clinical effects of duloxetine therapy on incontinence are small,
      suggesting that any benefits to the patient would be modest and must be weighed
      against the drug's adverse event profile. No comparative efficacy/tolerability
      data with alpha-receptor agonists (eg, pseudoephedrine) are available. On the
      basis of available data, duloxetine is a modest, but welcome, advance in the
      pharmacotherapeutic management of stress urinary incontinence.

PMID- 16089246
TI  - Economics of dementia and pharmacoeconomics of dementia therapy.
AB  - BACKGROUND: The economic impact of dementia is not well appreciated, even though
      Alzheimer's disease and related dementias were the third most expensive health
      condition in the United States in 2000. In 1997, the cost of managing patients
      with Alzheimer's disease and other dementias was estimated at US dollar 100
      billion. Direct medical costs are compounded by indirect costs of care, including
      unpaid care and loss of earnings. OBJECTIVE: The aim of this review was to
      examine studies of the economic impact of approved treatments for dementia
      therapy. METHODS: Searches of the MEDLINE database were conducted to identify
      prospective, randomized trials and retrospective or modeling studies of the
      economic impact of dementia medications, as well as analyses of managed care data
      (years 1996-2004; English language; search terms: dementia or Alzheimer's cross
      referenced with economic or costs). RESULTS: Only 3 studies directly examined the
      economic effects of dementia therapy. Two of these demonstrated economic benefits
      of treatment, whereas the third study concluded that there were no benefits;
      however, the conclusions of the latter study may have been weakened by such
      factors as the high rate of attrition and biased selection of study participants.
      Modeling studies and analyses of managed care data also indicate economic
      benefits from approved treatments. CONCLUSIONS: Therapies that are efficacious
      early in the disease can postpone the progression of dementia to more severe
      stages and may offer economic benefit to patients' families, caregivers, and
      society.

PMID- 16089247
TI  - Widening perspectives on pediatric rehabilitation.

PMID- 16089249
TI  - Paediatric traumatic brain injury: a review of pertinent issues.
AB  - Children with traumatic brain injury (TBI), regardless of the severity of the
      injury, often face challenges when living in home, school and community. Their
      needs are often overlooked and recognition of the long-term consequences is not
      always central to the management of the child in the school or community. This
      article provides references to pertinent literature and suggestions for
      intervention from the clinical experiences of four individuals with extensive
      experience of the family stresses, educational, cognitive-communicative and
      behavioural challenges that occur after TBI in children. It provides information
      regarding these issues, particularly educational situations, and suggests methods
      that may be useful for service providers and family members.

PMID- 16089250
TI  - Managing autism and Asperger's syndrome in current educational provision.
AB  - There is a need to understand the difficulties faced by those with autistic
      spectrum disorders (ASD) in educational settings if one is to manage and help
      them manage their learning. This paper explores some of the most pertinent
      problems that arise. It analyses perceptual, social, conceptual, emotional and
      memorizing barriers to learning and shows how difficulties in communication are
      exacerbated by educational language, which gives a poor model for those who have
      no prior understanding of inter-personal communication. The notion of an 'autism
      friendly' environment is examined as is the process of how schools and other
      learning institutions might be helped to create such an environment. Education as
      entitlement is distinguished from education as therapy and the implications for
      inclusion are examined. It is argued that the best teaching arises from an
      empathetic understanding and a willingness to be flexible, the worst, from
      rigidity and an expectation that it is the child who must change. There is no
      single approach that can meet all the needs of those with ASDs, but nor are needs
      entirely determined by individual behaviour. It is the understanding of ASD that
      enables the teacher to correctly identify the child's learning needs and begin to
      meet them.

PMID- 16089248
TI  - Educational approaches for maximizing arousal in children with multiple and
      severe disability: new directions for research and practice in early childhood
      contexts.
AB  - This paper provides a review of several critical issues and directions for
      research and practice, centred on children with multiple and severe disability,
      with special attention to the recent study of individual behaviour states as a
      measure of arousal and involvement. It notes several areas for future research
      and discusses educational interventions designed to improve the engagement of
      children, focusing on the central role of early intervention and human ecologies
      in supporting the achievement of positive educational outcomes for this
      population.

PMID- 16089251
TI  - Speech rehabilitation in 10 Spanish-speaking children with severe cerebral palsy:
      a 4-year longitudinal study.
AB  - A 4-year longitudinal intervention was conducted with 10 young severely
      dysarthric children with cerebral palsy. Two procedures were implemented, each
      one for a period of 2 years. The first procedure centred on training the oral
      praxies, whereas the second one favoured a more functional approach based on
      voice and prosody training as well as parents' and school teachers' involvement.
      Bobath neurodevelopmental treatment was given throughout the 4-year period.
      Results clearly favour the second type of procedure which in interaction with
      Bobath's technique proved able to bring the children from unintelligible to an
      acceptable level of functional speech.

PMID- 16089252
TI  - Saint or sinner? Teacher perceptions of a child with traumatic brain injury.
AB  - PURPOSE: To examine influences on classroom performance and behaviour following
      traumatic brain injury (TBI). METHODS: A case-study of one child who suffered a
      moderate TBI, with frontal brain damage, aged 8, followed up at ages 12 and 13
      years. Parents and child were interviewed to establish pre- and post-injury
      behaviour and functioning. All 19 teachers who taught the child reported on
      classroom performance, behaviour and educational achievement in each of their
      subjects. The child completed a comprehensive neuropsychological assessment
      battery including the Weschler Intelligence Scale for Children (WISC-III(UK)),
      Children's Memory Scale (CMS) and Vineland Adaptive Behaviour Scales (VABS).
      RESULTS: This child demonstrated above-average intelligence and good
      attention/concentration on the CMS. However, he was unable to focus or maintain
      attention in most classroom situations. His behaviour was erratic and disruptive
      in class and at home. At 5-year follow-up, his behaviour had deteriorated in both
      home and school situations, particularly in less structured environments.
      CONCLUSIONS: Teachers of more structured subjects (maths and science) perceived
      the child as excitable but performing at average or above-average levels, whereas
      teachers of less structured subjects (art, drama, music) perceived him to be
      'attention-seeking' and very disruptive in class. The influences of environmental
      factors are discussed.

PMID- 16089253
TI  - The relationship between school environment and participation for students with
      disabilities.
AB  - The aim of this study was to investigate the relationship between participation
      in school activities of students with disabilities and their school environment.
      Children and youths with disabilities rated their own participation in school
      activities while teachers and special education counsellors rated the student's
      school environment. Statistical methods used in this study were the Pearson's
      correlation coefficient and one-way-ANOVA. The results revealed that neither the
      amount of support given nor the general school environment was statistically
      related to students' participation. Further, the individual's specific
      environment, especially when rated as availability to activities by the students
      themselves, was related to students' participation. This might indicate that when
      investigating important environmental factors related to participation, students'
      own perceptions of his/her niches is important to investigate. The support
      students were given related more to type and number of disabilities than to
      students' participation.

PMID- 16089254
TI  - 'Must try harder?': a family empowerment intervention for acquired brain injury.
AB  - This paper describes an intervention aimed at empowering parents of child
      survivors of acquired brain injury (ABI) in their interaction with teachers and
      other professionals involved in their child's education. The particular
      characteristics of the late morbidity of child ABI led to the design of an
      intervention in the form of a video and informational booklet that is the
      property of the family. Early response to the intervention has been extremely
      positive, although formal evaluation has been unexpectedly challenging.

PMID- 16089255
TI  - Developing behavioural services to meet defined standards within a national
      system of specialist education services.
AB  - In response to increasing demand for more accountability and improved outcomes in
      the provision of behavioural services, Specialist Education Services (SES) in New
      Zealand employed the trainer of trainers programme developed by the Institute for
      Applied Behaviour Analysis (IABA). The goal was to develop a national training
      team capable of training SES staff to carry out assessments and develop support
      plans that could meet defined standards. The purpose of this study was to
      evaluate the outcomes of this trainer of trainers project. The primary methods of
      evaluation included the pre-post training comparisons of trainees' functional
      assessments and positive behaviour support plans, against 140 defined criteria.
      The results of this project indicated that the SES national training team was
      able to train SES staff to meet the same standards of service delivery as the
      external IABA trainers. Further, a Periodic Service Review (PSR) system was
      implemented to insure that service standards could be maintained at a high level.
      A major conclusion reached in this study was that a trainer of trainer approach
      appears to be effective in preparing large numbers of educational personnel to
      meet the increasing demands by schools for professionals to meet a high standard
      of service delivery.

PMID- 16089256
TI  - A comparison of developmental versus functional assessment in the rehabilitation
      of young children.
AB  - BACKGROUND: The purpose of this study was to explore the differences in and
      potential uses of information derived from developmental vs. functional
      assessment during the acute rehabilitation of very young children with acquired
      brain injury. Both methods of assessment are typically used during
      hospitalization in order to assist in developing individualized goals and outcome
      measures. With the trend of shortened hospital stays, effective assessment for
      determining optimal treatment goals and outcomes becomes increasingly important.
      The results from a developmental and a functional assessment obtained on 23
      inpatient children below 6 years of age who had experienced either an acquired
      brain injury or encephalitis were compared. The data was collected through a
      retrospective chart review spanning 4 years. METHODS AND OUTCOME MEASURES: Each
      child received a cognitive and a language test using either the Early Learning
      Accomplishment Profile (E-LAP) or the Learning Accomplishment Profile Diagnostic
      (LAP-D) for the developmental assessment measure. The Functional Independence
      Measure for Children (WeeFIM) was used as a functional assessment. Summary
      statistics and frequencies were calculated for variables including age and
      diagnosis. Partial Pearson correlations and 95% confidence intervals were
      calculated between the functional and developmental assessments, adjusting for
      the amount of time between administrations of the two exams. Pearson correlations
      were computed between length of hospital stay and performance on the
      developmental and functional quotients. RESULTS: Moderate, statistically
      significant Pearson partial correlations were found between the E-LAP/LAP-D
      cognitive quotient and the WeeFIM cognitive quotient (r = 0.42, 95% CI (0,
      0.72)), the E-LAP/LAP-D language quotient and the WeeFIM cognitive quotient (r =
      0.55, 95% CI (0.17, 0.79)) and the E-LAP/LAP-D cognitive quotient and the WeeFIM
      total quotient (r = 0.50, 95% CI (0.10, 0.76)). An inverse correlation was found
      between the length of stay and the E-LAP/ LAP-D cognitive quotient (r = -0.68,
      95% CI (-0.86, -0.34)) as well as the E-LAP/LAP-D language quotient (r = -0.61,
      95% CI (-0.83, -0.23)). CONCLUSIONS: The moderate but limited correlations
      between developmental and functional assessments may be attributed to differences
      in the two forms of assessment including the test items, their administration and
      scoring. While both forms of assessment were thought to be useful for developing
      individualized treatment goals and measuring outcomes, there were advantages and
      disadvantages to each.

PMID- 16089257
TI  - Radiographic evaluation of cervical spine of subjects with temporomandibular
      joint internal disorder.
AB  - Although the etiopathophysiology of internal temporomandibular joint internal
      disorders (TMJ ID) is still unknown, it has been suggested that head and body
      posture could be related to its initial onset, development and perpetuation. The
      purpose of the present study was to observe the relationship between cervical
      spine X-ray abnormalities and TMJ ID. This investigation evaluated 30 subjects
      with internal TMJ disorder symptoms (test group) and 20 healthy subjects (control
      group). Subjects were submitted to clinical and radiographic evaluation. Clinical
      evaluation comprised anamnesis and stomatognathic system physical examination.
      Radiographic evaluation comprised analysis of lateral cervical spine X-rays by
      three physical therapists and tracing on the same images. The test group
      presented twice as much cervical spine hyperlordosis as the control group (20.7%
      versus 10.5%), but almost half of rectification prevalence (41.4 versus 79.0%, p
      = 0.03). After that, the test group was divided into three subgroups according to
      TMJ dysfunction severity, evaluated by Helkimo's index. These subgroups were not
      significantly different, but the subgroup with more severe TMD showed a tendency
      to cervical spine hyperlordosis prevalence. Results showed a tendency for
      subjects with more severe TMD to exhibit cervical spine hyperlordosis.
      Nevertheless, studies with a larger number of subjects suffering from severe TMD
      are encouraged in order to corroborate the present findings.

PMID- 16089258
TI  - Effect of conventional TENS on pain and electromyographic activity of masticatory
      muscles in TMD patients.
AB  - Temporomandibular disorders (TMD) are characterized by several signs and
      symptoms, such as pain and changes in the electrical activity of masticatory
      muscles. Considering that transcutaneous electrical nerve stimulation (TENS) is a
      resource indicated to promote analgesia, the objective of this study was to
      evaluate the effect of TENS on pain and electromyographic (EMG) activity of the
      jaw elevator muscles in TMD patients. This study evaluated 35 female volunteers:
      19 TMD patients (mean age = 23.04 +/- 3.5) and 16 normal subjects (mean age =
      23.3 +/- 3.0). Transcutaneous electrical nerve stimulation (conventional mode,
      150 Hz) was applied once to each group for 45 minutes. Surface electromyography
      (gain of 100 times and 1 kHz sampling frequency) and the visual analogue scale
      (VAS) were applied before and immediately after TENS application. Both VAS data
      and root mean square (RMS) values were analyzed using Student's t-test. The TMD
      group, compared to the control group, showed higher EMG activity of the jaw
      elevator muscles at rest. No difference was observed between the groups regarding
      maximum voluntary clenching (MVC). In TMD patients, TENS reduced both pain and
      EMG activity of the anterior portion of the temporal muscle, increasing the
      activity of the masseter muscles during MVC. It is possible to conclude that a
      single TENS application is effective in pain reduction. However, it does not act
      homogeneously on the features of the electric activity of the muscles evaluated.

PMID- 16089259
TI  - Effect of instruction and motivation in the use of electric and manual
      toothbrushes in periodontal patients. A comparative study.
AB  - The aim of the present study was to evaluate the efficacy of manual and electric
      toothbrushes in plaque control in periodontal patients after proper instructions.
      Thirty six periodontal patients (mean age of 49 years, 21 females and 15 males)
      were included and completed the study (100% compliance). A single-blinded,
      randomized, controlled, cross-over clinical design was adopted, with the patients
      using during 2 periods of 14 days each the manual and/or electric toothbrush.
      Four subgroups of 9 individuals were studied: A1--used manual toothbrush in both
      experimental periods; A2--used the manual toothbrush during the first period and
      the electrical toothbrush during the second period; B1--used electrical
      toothbrush during both periods; B2--used the electrical toothbrush in the first
      period and the manual one in the second period. Brushing was performed during 14
      days and at day 14 and 28 it was performed in the clinic, and timing of brushing
      was recorded without patients being aware. The Plaque Index (Silness, Loe, 1964)
      was used. Intra-group comparisons were performed by paired t-test and inter-group
      comparisons by independent sample t-test, with an alpha level of 0.05. The
      results showed no difference between the tested brushes neither for plaque nor
      for timing. However, re-instruction was detected as an important factor, since
      for all groups the second period, after reinstruction, showed lower plaque
      scores. It is concluded that professional advice and instruction and re
      instruction seem more important in order to obtain good plaque control than the
      choice of toothbrush in subjects with periodontal disease.

PMID- 16089260
TI  - Periodontal conditions of teeth presenting pathologic migration.
AB  - The aim of the present study was to evaluate the periodontal conditions of
      anterior teeth that presented pathologic migration in patients with chronic
      periodontitis and to compare periodontal destruction in migrated versus non
      migrated teeth. The sample included 32 patients of both sexes (mean age: 46.0 +/-
      11.6 years) diagnosed with generalized chronic periodontitis and selected on the
      basis of the presence of pathologic migration in one or more anterior teeth. This
      migration was classified according to the following categories: facial flaring,
      diastema, proximal tilting, rotation or extrusion. The periodontal parameters
      recorded were clinical attachment loss (CAL) and percentage of radiographic bone
      loss (BL). Mean CAL of 5.50 +/- 2.20 mm and mean BL of 41.90 +/- 15.40% were
      found in 115 teeth assessed. The most frequent type of migration was facial
      flaring (34.80%), followed by diastema (27.00%). Extrusion was hardly observed in
      the sample (4.30%). However, greater severity of BL and CAL were observed in
      teeth with this type of migration (59.44% and 8.42 mm, respectively), and in
      teeth with facial flaring (45.17% of BL and 6.07 mm of CAL). Kruskal-Wallis test
      indicated that BL presented by teeth with extrusion or facial flaring was greater
      than that observed in rotated or tilted teeth (p < 0.05), while there was no
      difference between groups regarding CAL (p = 0.11). It was observed that anterior
      teeth with pathologic migration presented greater CAL and BL (5.1 mm and 40%)
      than non-migrated teeth (4.1 and 31%). The study indicated that the most
      prevalent kind of pathologic migration is facial flaring, which was associated to
      higher level of bone loss.

PMID- 16089261
TI  - Peroxide bleaching agent effects on enamel surface microhardness, roughness and
      morphology.
AB  - The aim of this study was to evaluate the surface roughness, microhardness and
      morphology of human enamel exposed to six bleaching agents (at baseline and post
      treatment). Human dental enamel samples were obtained from human third molars and
      randomly divided into seven groups (n = 11): control, Whiteness Perfect--10%
      carbamide peroxide (10% CP), Colgate Platinum--10% CP, Day White 2Z--7.5%
      hydrogen peroxide (7.5% HP), Whiteness Super--3% CP, Opalescence Quick--35% CP
      and Whiteness HP--35% HP. Bleaching agents were applied according to
      manufacturers' instructions. The control group remained not treated and stored in
      artificial saliva. Microhardness testing was performed with a Knoop indentor and
      surface roughness was analyzed with a profilometer. Morphologic observations were
      carried out with scanning electron microscopy (SEM). Results were statistically
      analyzed by two-way analysis of variance and Tukey's test (5%), and revealed a
      significant decrease in microhardness values and a significant increase in
      surface roughness post-bleaching. Changes in enamel morphology after bleaching
      were observed under SEM. It was concluded that bleaching agents can alter the
      microhardness, roughness and morphology of dental enamel surface.

PMID- 16089262
TI  - Evaluation of microleakage in human, bovine and swine enamels.
AB  - The suitability of bovine and swine teeth has been evaluated when they are used
      as substitutes for extracted human teeth in varied researches. This study
      evaluated in vitro the marginal microleakage in human, bovine and swine enamel.
      Cubic cavities (2 x 2 x 2 mm3) were prepared in enamel blocks from human, swine
      and bovine teeth. The cavities were filled with composite resin and conventional
      glass-ionomer cement. All the samples were thermocycled for 1,000 cycles (5 +/- 2
      degrees C - 55 +/- 2 degrees C) and immersed in 2% methylene blue solution for 12
      hours. The microleakage was quantified by a spectrophotometric technique. The
      results were statistically analyzed using ANOVA and Tukey's test. The glass
      ionomer cement presented significantly higher leakage means (microg/ml +/- SD)
      than the composite resin for all substrates (0.0695 +/- 0.01313 vs. 0.0471 +/-
      0.0163, p < 0.01). No significant differences were found between bovine and swine
      enamel (0.0668 +/- 0.0246 vs. 0.0674 +/- 0.0286); however, both presented
      statistically higher leakage means than human enamel (0.0407 +/- 0.0195, p <
      0.01). It was concluded that the microleakage pattern was affected by substrates,
      and that bovine and swine substrates allow higher marginal leakage than human
      substrates. The results indicate there should be precaution in the substitution
      of human substrate in laboratory studies of microleakage.

PMID- 16089263
TI  - Sealing ability of MTA, Super EBA, Vitremer and amalgam as root-end filling
      materials.
AB  - This study evaluated the root-end sealing ability of mineral trioxide aggregate
      (MTA Angelus), reinforced zinc oxide-eugenol cement (Super EBA), resin-modified
      glass ionomer (Vitremer) and zinc-free amalgam (GS-80) (control). The root canals
      of eighty human lower molars were accessed, cleansed, shaped and obturated.
      Apexes were resected and cavities were prepared. Teeth were divided into 4 groups
      of 40 cavities, root-end filled with the materials, and immersed in methylene
      blue for 72 h at 37 degrees C. Roots were then sectioned transversally at each
      millimeter and evaluated under magnification, observing the dye penetration in
      each section. Data were evaluated using Kruskal-Wallis test at a 5% level of
      significance, showing the differences among all materials (p < 0.001). The
      crescent order of microleakage was MTA < Vitremer < Super EBA < amalgam. Higher
      leakage levels were observed in the first millimeter sections of amalgam,
      Vitremer and MTA, when compared with the third millimeter section (p < 0.05).

PMID- 16089264
TI  - Facial fractures: a 1-year retrospective study in a hospital in Belo Horizonte.
AB  - A retrospective study was performed to assess facial fractures in patients
      treated at a public hospital in Belo Horizonte, in 2000. The data collected
      included age, gender, etiology, distribution of maxillofacial trauma considering
      day of the week and month, anatomic site of the fracture, and treatment. The
      analyses involved descriptive statistics and chi-squared test, Bonferroni test
      and analysis of variance. A total of 1,326 facial fractures were found in 911
      patients. Most fractures occurred in adults with age ranging from 21 to 30 years.
      Men were more affected than women, with a male-female ratio of 4.69:1. Accidents
      causing facial fractures occurred predominantly on weekends. Bicycle and
      motorcycle accidents were the major cause of trauma, followed by interpersonal
      violence, automobile accidents, and falls. When the relation between the gender
      and the etiology of facial fractures was analyzed, a significant relation was
      noted between these variables (p < 0.001). There was also a relation between the
      patients' age and the site of the fractures (p = 0.0014). The mandible was found
      to be the most commonly fractured bone in the facial skeleton, followed by the
      zygomatic complex and the nose. A non-surgical approach was chosen in most cases.
      There were significant differences between the kind of treatment applied and the
      site of the fracture (p < 0.001).

PMID- 16089265
TI  - Tooth ankylosis in deciduous teeth of children with cleft lip and/or palate.
AB  - The present study aimed at evaluating the prevalence of tooth ankylosis in
      deciduous molars of Caucasian children with cleft lip and/or palate aged 5 to 12
      years, of both genders. A total of 330 patients seen at the Hospital for
      Rehabilitation of Craniofacial Anomalies of the University of Sao Paulo for
      routine treatment were clinically evaluated. The prevalence of ankylosis was
      analyzed in relation to gender, age range (5-7, 8-10, 11-12 years), type of
      cleft, affected tooth and arch. The total group showed a prevalence of 18%, with
      no statistical difference between genders and among types of cleft; ankylosis was
      more often in the mandibular arch, lower first molars and among children in the
      age ranges 8-10 and 11-12 years. The results agreed with those observed in the
      related literature for patients without clefts, pointing out the absence of
      influence of the cleft on the prevalence of ankylosis. This reinforces the
      importance of early diagnosis of this anomaly and of the treatment of choice,
      which are similar in patients with or without clefts.

PMID- 16089266
TI  - Relation between speaking space of the /s/ sound and freeway space in dentate and
      edentate subjects.
AB  - The purpose of this study is to assess the relation between the speaking space of
      the /s/ sound and the freeway space in two subject groups. One group had natural
      dentition (Group I, n = 61) and the other comprised complete denture wearers
      (Group II, n = 33). The analysis was done by means of a jaw-tracking device (K6-I
      Diagnostic System, Myotronics Research Inc., Seattle, WA, USA). Freeway space was
      determined by asking the subjects to occlude from the postural rest position.
      Speaking space of /s/ was measured during the pronunciation of the word "seis"
      and comprised the mean distance from the /s/ speaking position to maximal
      intercuspation. A weak correlation was found between the speaking space of /s/
      and the freeway space in Group I (r = 0.41, p < 0.01), but in Group II, the
      correlation was stronger (r = 0.75, p < 0.01). The speaking space of /s/ and
      freeway space were different in Group I, but statistically similar in Group II
      (paired t-test, alpha = 0.05). It can be suggested that anatomic changes
      following prosthetic procedures caused a functional adaptation which resulted in
      more similar values for the speaking space of /s/ and the freeway space.

PMID- 16089267
TI  - CT-based analysis of malignant tumor volume and localization. A preliminary
      study.
AB  - The purpose of this study was to correlate 3D-CT (3D computed tomography) volume
      measurements of malignant tumors with the response to treatment, and to observe
      bone invasion in these lesions applying a specific imaging protocol. We analyzed
      17 individuals with maxillofacial malignant lesions who were submitted to spiral
      CT (2D-CT). The original data were transferred to an independent workstation
      using a 3D volume rendering package software, which was used by two examiners to
      obtain area and volume measurements of the lesions, independently, three times
      each, prior to and after treatment. The segmentation protocol was applied for the
      assessment of bone involvement. The difference between imaging and gold standard
      values was not considered significant (p > 0.05). Regarding bone invasion, three
      false-negatives were obtained using MPR-CT (multiplanar reconstruction) and no
      false-negatives were obtained using the 3D segmentation protocol. The use of 3D
      CT may be a differential and important factor for expanding options regarding the
      localization, dimension, and clarification of lesion components.

PMID- 16089268
TI  - Histologic evaluation of the effect of nicotine administration on bone
      regeneration. A study in dogs.
AB  - The objective of this study was to investigate the histometric impact of nicotine
      on bone regeneration of surgically created alveolar ridge defects in dogs.
      Sixteen mongrel dogs were used. One defect was surgically created unilaterally in
      the mandible, and left to heal spontaneously. The animals were randomly assigned
      to one of the following groups: Group 1--control (n = 8) and Group 2-
      subcutaneous nicotine administration (2 mg/kg) twice a day (n = 8). After 4
      months, the animals were sacrificed and the specimens routinely processed for
      semi-serial decalcified sections. Bone height (BH), bone width (BW), bone density
      (BD), and bone area (BA) of the newly-formed bone were evaluated. Intergroup
      analysis (Mann-Whitney rank sum test) showed that regardless of the presence of
      nicotine, no significant differences were observed regarding bone width (BW),
      bone area (BA) and bone height (BH) (p > 0.05). On the other hand, it was
      demonstrated that nicotine administration significantly influenced the proportion
      of mineralized tissue within the limits of the newly-formed bone (BD) (p <
      0.001). Within the limits of the present study, it can be concluded that nicotine
      might affect but not prevent bone healing in defects left to heal spontaneously.

PMID- 16089269
TI  - Correlation among mutans streptococci counts, dental caries, and IgA to
      Streptococcus mutans in saliva.
AB  - Two-hundred and forty individuals were studied, divided into five groups as
      follows: caries-free children, children with caries, children with rampant
      caries, young adults with and without caries. Whole stimulated saliva was
      collected and all individuals were investigated for DMFT/dmft according to the
      WHO criteria and the simplified oral hygiene index (OHI-S). Quantitative analysis
      of the total aerobic flora and mutans streptococci in saliva was performed. Also,
      the level of salivary anti-S. mutans IgA was determined by ELISA. Children with
      rampant caries showed the highest OHI-S value. The highest total counts of
      microorganisms were found in the group of children with caries. No statistically
      significant differences were observed for salivary flow, OHI-S and microorganism
      counts between the groups of young adults. No correlation between mutans
      streptococci counts and anti-Streptococcus mutans IgA levels was observed in the
      studied groups. A correlation between increased anti-Streptococcus mutans IgA
      levels and caries-free status was observed among young adults but not among
      children.

PMID- 16089270
TI  - Variability in exercise capacity and metabolic response during endurance exercise
      after a low carbohydrate diet.
AB  - The impact of altered blood glucose concentrations on exercise metabolism and
      performance after a low carbohydrate (CHO) diet was investigated. In random
      order, 1 wk apart, 9 trained men underwent euglycemic (CI) or placebo (PI)
      clamps, while performing up to 150 min of cycling at 70% VO2(max), after 48 h on
      a low CHO diet. The range in improvement in endurance capacity with glucose
      infusion was large (28 +/- 26%, P < 0.05). Fifty-six percent of subjects in CI
      failed to complete 150 min of exercise despite maintenance of euglycemia, while
      only 2 subjects in PI completed 150 min of exercise, despite being hypoglycemic.
      Total CHO oxidation remained similar between trials. Despite longer exercise
      times in CI, similar amounts of muscle glycogen were used to PI. Maintenance of
      euglycemia in the CHO-depleted state might have an ergogenic effect, however, the
      effect is highly variable between individuals and independent of changes in CHO
      oxidation.

PMID- 16089271
TI  - Should carbohydrate concentration of a sports drink be less than 8% during
      exercise in the heat?
AB  - Our purpose was to determine if sports drinks with 6 and 8% CHO differentially
      affect physiological responses or run performance in the heat. Ten men ran 32 km
      while ingesting: placebo (P), 6% carbohydrate-electrolyte (CE6), and 8%
      carbohydrate-electrolyte (CE8). At 15 km, a 250 mL drink labeled with deuterium
      oxide (D2O) was ingested. Blood glucose and respiratory exchange ratio were
      significantly higher (P < 0.05) for CE6 and CE8 compared to P. Rectal temperature
      (T(re)) at 32 km was higher for CE8 (40.1 +/- 0.2 degrees C) compared to P (39.5
      +/- 0.2 degrees C) but similar to CE6 (39.8 +/- 0.2 degrees C). D2O accumulation
      was not different among drink trials. Run performance was 8% faster for CE8 (1062
      +/- 31 s) compared to P (1154 +/- 56 s) and similar to CE6 (1078 +/- 33 s).
      Confirming the ACSM Position Stand, 8% CE are acceptable during exercise in the
      heat and attenuate the decline in performance.

PMID- 16089272
TI  - Oxidative stress and antioxidants in athletes undertaking regular exercise
      training.
AB  - Exercise has been shown to increase the production of reactive oxygen species to
      a point that can exceed antioxidant defenses to cause oxidative stress. Dietary
      intake of antioxidants, physical activity levels, various antioxidants and
      oxidative stress markers were examined in 20 exercise-trained "athletes" and 20
      age- and sex-matched sedentary "controls." Plasma F2-isoprostanes, antioxidant
      enzyme activities, and uric acid levels were similar in athletes and sedentary
      controls. Plasma alpha-tocopherol and beta-carotene were higher in athletes
      compared with sedentary controls. Total antioxidant capacity tended to be lower
      in athletes, with a significant difference between male athletes and male
      controls. Dietary intakes of antioxidants were also similar between groups and
      well above recommended dietary intakes for Australians. These findings suggest
      that athletes who consume a diet rich in antioxidants have elevated plasma alpha
      tocopherol and beta-carotene that were likely to be brought about by adaptive
      processes resulting from regular exercise.

PMID- 16089273
TI  - Cognitive dietary restraint is associated with stress fractures in women runners.
AB  - High levels of cognitive dietary restraint (CDR) have been associated with
      subclinical menstrual cycle irregularities and increased cortisol levels, both of
      which can affect bone mineral density (BMD). Low BMD has been implicated in
      stress fracture risk. We assessed CDR in female runners (> or = 20 km/wk) with a
      recent stress fracture (SF) and with no stress fracture history (NSF). A sample
      of 79 runners (n = 38 SF, 29 +/- 5 y; n = 41 NSF, 29 +/- 6 y) completed a 3-d
      food record and questionnaire assessing physical activity, menstrual cycle
      history, and perceived stress. SF and NSF runners had similar body mass index
      (21.2 +/- 1.8 vs. 22.0 +/- 2.5 kg/m2), physical activity (35.7 +/- 13.5 vs. 33.4
      +/- 1.34 km/wk), perceived stress, and dietary intakes. CDR, however, was higher
      in SF runners (11.0 +/- 5.4 vs. 8.4 +/- 4.3, P < 0.05). Subclinical menstrual
      cycle disturbances and increased cortisol levels that are associated with high
      CDR, might in turn contribute to lowered BMD and increased stress fracture risk.

PMID- 16089274
TI  - Nutritional strategies of mountain marathon competitors--an observational study.
AB  - Mountain marathons are 2-d, self-supported adventure races, during which
      competitors must carry all nutritional requirements to sustain athletic effort.
      This requires a compromise between the energy required to perform and the weight
      penalty of carrying it. We have undertaken a nutritional survey of event
      competitors in the UK using a questionnaire-based approach and have monitored
      dehydration during the event. We found that competitors in longer-distance
      classes (> 50 km) carry significantly less mass of food, which is more energy
      dense, but that the calorific value is lower than that of competitors in shorter
      classes. Carbohydrate and protein consumption both positively associated with
      performance. Competitors became progressively dehydrated throughout the event.
      Counterintuitively, the better-performing subjects became the most dehydrated.
      Competitors at all distances should make more effort to rehydrate during breaks
      in the event. Competitors at shorter distances could choose more energy-dense
      foods to reduce weight penalty.

PMID- 16089275
TI  - Ingestion of tyrosine: effects on endurance, muscle strength, and anaerobic
      performance.
AB  - Acute tyrosine ingestion is thought to improve aerobic endurance, muscle strength
      and endurance, and anaerobic power of men undergoing severe physiologic stress.
      In a double-blind, crossover study, 20 men (32 +/- 1 y old) underwent 2
      loadcarriage treadmill sessions, 1 after taking tyrosine (150 mg/ kg L
      crystalline tyrosine) and 1 after taking placebo. Tyrosine dosage was based on
      subject weight and ingested 30 min before load carriage. A physical performance
      battery was administered after the load carriage: maximal and submaximal
      handgrip, pull-ups, and stair stepping with weight. Total time on treadmill was
      not significantly lengthened with ingestion of tyrosine (118.9 +/- 1.4 min) as
      compared with placebo (119.2 +/- 1.2 min). Total power for stair stepping
      (tyrosine 223 +/- 8 watts, placebo 216 +/- 9 watts) and muscle strength and
      endurance (handgrip) was not significantly improved by tyrosine ingestion. The
      results indicate that acute ingestion of tyrosine by healthy men has no
      measurable effect on endurance, muscle strength, or anaerobic power.

PMID- 16089276
TI  - Validation of a new handheld device for measuring resting metabolic rate and
      oxygen consumption in children.
AB  - The purpose of this study was to assess the validity and reliability of the
      MedGem device to measure resting metabolic rate (RMR) in children. Subjects
      included 59 children (29 boys, 30 girls; mean age, 11.0 +/- 0.2 y). Subjects were
      given 4 RMR tests during 1 test session, cconsisting of 2 Douglas bag and 2
      MedGem tests, in random counterbalanced order. No significant differences were
      found between Douglas bag and MedGem systems for oxygen consumption (209 +/- 5
      and 213 +/- 5 mL/min, respectively, P = 0.106, r = 0.911, mean +/- standard
      deviation absolute difference 3.72 +/- 17.40 mL/min) or RMR (1460 +/- 39 and 1477
      +/- 35 kcal/d, P = 0.286, r = 0.909, mean +/- standard deviation absolute
      difference 17.4 +/- 124 kcal/d). Standard error of estimates for oxygen
      consumption and RMR were 17.4 mL/min and 124 kcal/d, respectively. In conclusion,
      these data indicate that the MedGem is a reliable and valid system for measuring
      oxygen consumption and RMR in children.

PMID- 16089277
TI  - Dietary supplement use by varsity athletes at a Canadian university.
AB  - The purpose of this study was to assess reasons for and prevalence of supplement
      use among varsity athletes and nonvarsity athlete students (controls) at a
      Canadian university. A questionnaire, distributed to 247 varsity athletes and 204
      controls, included variables regarding sports participation, supplements used,
      reasons for usage, perceived effects, and areas of interest about supplements.
      Response rates were 85.5% among varsity athletes and 44.6% among controls.
      Supplements were used by 98.6% of varsity athletes and 94.3% of controls. Varsity
      men most often reported using sports drinks, and used these (and carbohydrate
      gels, protein powder, and creatine) more than varsity women. Caffeine products
      were most often reported by other groups. Health professionals and the Internet
      were the most reported information sources, while friends most often recommended
      supplements. Many subjects indicated knowing little about supplements and wanting
      to learn more. Results indicate a need for nutrition education among both varsity
      athletes and university students.

PMID- 16089278
TI  - [Education and evaluation].

PMID- 16089279
TI  - [Diabetes mellitus: causes for hospitalization, intrahospital complications and
      mortality].
AB  - OBJECTIVE: To determine hospitalization causes, complications and mortality in
      Mexican patients with diabetes mellitus (DM). METHODS: Between July and December
      2001, we reviewed all admissions to the Department of Internal Medicine. Patients
      with a diagnosis of DM were included. A structured questionnaire was applied with
      the assessment of the following variables: sociodemographic; clinical history;
      variables associated with DM (complications associated with DM, treatment and
      diet, control of the disease by general practitioner or specialist); admissions
      (causes, length of stay, complications, glycemia at onset of admission and causes
      of death). RESULTS: One hundred forty-seven patients were hospitalized, 57% were
      women with a mean age of 58 years and disease duration of 165 months; 43% knew
      their glycemia value upon admission and 67% were seen in the outpatient clinic 30
      days previous to admission. At onset of hospitalization 61% were hyperglycemic,
      5% had hypoglycemia and 22% had normal glycemic values. The causes of
      hospitalization were cardiovascular diseases (37%), complications associated with
      DM (20%), and infections (18%). The mean length of hospital stay was 10 days.
      There were 16 (11%) deaths specifically due to cardiovascular disease.
      CONCLUSIONS: Frequent causes of hospitalizations, intrahospital complications and
      deaths were similar to previous studies in other countries.

PMID- 16089280
TI  - [Coexistent morbidity in chronic and hypertrophic adenotonsillitis: a case study
      in 3600 subjects].
AB  - OBJECTIVE: To know the frequency of chronic and hypertrophic adenotonsillitis,
      affected population, coexisting morbidity and surgical procedures in a population
      of Zone 89, IMSS at Guadalajara, Jalisco. MATERIALS AND METHODS: Descriptive,
      transversal and prospective study of patients with diagnosis of chronic and
      hypertrophic adenotonsillitis treated between January 2000 and October 2001 were
      studied. Through age groups were analyzed coexisting morbidity and surgical
      procedures. RESULTS: Of the 3600 patients with chronic and hypertrophic
      adenotonsillitis evaluated, they were distinguished 3 age groups that are
      characterized by coexisting morbidity, the average age group (45%) was between 6
      to 10 years and characterized by the presence of chronic sinusitis, otitis media
      with effusion and recurrent otitis media; while the children younger than 5 years
      (30.3%) prevailed the obstruction of the upper respiratory tract, chronic
      sinusitis, bronchitis and otitis media with effusion; however, all individuals
      aged from 16 to 49 years (9.4%) was notary the presence of chronic otitis media
      and peritonsillar abscess. CONCLUSIONS: The present study represented the first
      step for future studies and permitted us to understand the frequency and
      coexisting morbidity of this pathology in our medium. The usefulness of this
      study will contribute to the promotion of prevention measures, opportune
      detection of complications, acquire new methods of bacteriologies diagnostics and
      therapeutic strategies. It is possible that new prevention measures will chain
      react a new series of events that will translate into a reduction of this
      pathology, surgeries and complications.

PMID- 16089281
TI  - [Critical reading ability in research during medical internship].
AB  - OBJECTIVE: To evaluate level of development that medical interns achieve, before
      graduating, in critical reading ability during their internship in five general
      hospitals. MATERIAL AND METHODS: During the academic year, we compared the
      initial and final scores of critical reading of medical interns before graduation
      in five general hospitals in IMSS. An instrument using 98 items that explored
      interpretation, judgment and proposal was developed and validated by four medical
      education researchers. In hospitals 1, 4, and 5, professors developed active
      participative strategies related to critical reading in clinical research. In
      Hospital 2, no course was given and in Hospital 3, a traditional course (mainly
      clinical exposure) was offered. RESULTS: The final global scores were better for
      those students in Hospitals 1, 4 and 5 versus Hospitals 2 and 3 (median: 31, 29,
      31 versus 9 and 24) (Kruskal-Wallis < 0.05). Initial and final differences in
      global and interpretation, judgment and proposal were also better in those same
      students. CONCLUSIONS: Active-participative educational strategies may develop
      the ability for critical reading of clinical research in internship and these
      strategies must be included in the curriculum during internship.

PMID- 16089282
TI  - [Impact of an active educational strategy in arterial hypertension].
AB  - OBJECTIVE: To evaluate the efficacy of an active-participative educational
      intervention on the average arterial pressure, index of corporal mass and level
      of knowledge in hypertensive patients. METHODS: A quasi-experimental open study
      was carried out. An active-participative educational intervention 4 h daily
      during a period of 5 days twice monthly for 3 months focused on themes related to
      arterial hypertension in patients with high blood pressure. No control subjects
      were included. Subject to acceptance and after informed consent, 48 patients (25
      60 years of age) were included with slight and moderate arterial hypertension.
      Patients with evidence of severe organ damage or with chronic underlying disease
      were excluded. The impact of the educational intervention was evaluated based on
      the increase of knowledge, improvement of weight (IMC), and average arterial
      pressure, taking into consideration 2, 4, and 6 months of the educational
      strategy. Descriptive statistics were utilized for analyzing results using
      Student's ttest. RESULTS: The level of knowledge increased 31.30 points in the
      population studied and there was a decrease of the IMC of 2.75 points after
      educational intervention (p < 0.05). The decrease in weight, as well as the
      arterial pressure, showed statistically significant differences with respect to
      the initial measurements, with a difference of the PAM of 13.69 mm Hg at the
      conclusion of the study (p < 0.05). CONCLUSIONS: An active-participative
      educational strategy is useful in the control of the PAM and IMC in the
      hypertensive patient.

PMID- 16089283
TI  - [Pharmacosurveillance III: international experience].
AB  - This article, the third of the series called pharmacovigilance, deals with
      international experience with adverse drug reactions. It highlights the countries
      with the greatest cumulative number of reports and how their position changes
      with the use of the country-adjusted number of reports by million of
      inhabitants/year. It includes, in decreasing order, the number of reports of
      twenty therapeutic drug classes. Included in each one are the most plausible
      explanations for their frequency and, finally, the cumulative number of reports
      for clinical manifestations of adverse drug reactions.

PMID- 16089284
TI  - [The training of specialists at the Instituto Mexicano de Seguro Social. Towards
      a new evaluation system].
AB  - We present the new system for the evaluation of the medical specialization
      courses at the IMSS which will substitute in 2005 the one used at present. This
      system derives from a participative conception of education and has as an axis
      the development of aptitudes. For participative education, knowledge is the
      result of the student's elaboration, and not the result of the consumption of
      information. An aptitude is the conjunction of knowledge, abilities and attitudes
      in a constant development which gives the bearer experience a growing penetration
      to understand the problematic situations that challenge him, a greater reach of
      the decisions and actions performed and progressive pertinence to positively
      influence the working environment. The new evaluation system is centered in the
      development of two types of aptitude: the clinical aptitude and the aptitude for
      the appropriate use of information sources. It has an explanatory and
      instructions section, as well as four types of forms: (a) evaluation of the
      aptitudes development through time. (b) Performance of activities (in the service
      and academic) related with the aptitudes seeking to develop. (c) Evaluation of
      the academic and working environment, and (d) self evaluation. With the new
      system of evaluation of the formation of medical specialists we pretend to
      contribute to the overcoming of the educative labors at the Institute, by
      orienting the professors' and students' reflection towards the main aspects of
      learning, as well as promote the criticism and self-criticism.

PMID- 16089285
TI  - [Incidence of dentofacial deformities in the Specialty Hospital of the Instituto
      Mexicano del Seguro Social].
AB  - OBJECTIVE: To report the incidence and classification of dentofacial deformities
      from the Maxillofacial Department at the Specialty Hospital at the 21st Century
      National Medical Center of the Mexican Institute of Social Security in Mexico
      City. A descriptive, retrospective and transversal study was carried out.
      MATERIAL AND METHODS: Clinical files from 120 patients were reviewed from May
      1997 to May 1998 with the purpose of classifying and determining the types of
      maxillofacial deformities and also to report whether these deformities were
      corrected by orthognatic surgery. RESULTS: One hundred twenty clinical files were
      reviewed and dentofacial deformities were found in 47 (39%). All patients were
      treated with orthognatic surgery. Surgical treatment was often combined
      (orthodontia and surgery). CONCLUSIONS: Regardless of the type of dentofacial
      deformities, an individualized treatment protocol must be designed for each
      patient. It is important to list the priorities and needs of the patients in
      order to find appropriate solutions, in regard to their importance.

PMID- 16089286
TI  - [A case of small-cell malignant melanoma in a pregnant patient].
AB  - INTRODUCTION: Malignant melanoma (MM) is an aggressive neoplasm that may affect
      pregnant women. Malignant melanoma with small-cell morphology (MMSCM) is a rare
      variant of MM that can cause confusion in its diagnosis. OBJECTIVE: To report a
      fatal case of MMSCM in a pregnant woman, highlighting immunohistochemistry (IHC)
      as a very useful tool in the final diagnosis. CLINICAL CASE: A 22-year-old
      pregnant female presented with a 5-cm cutaneous tumor in her right leg. The
      lesion was excised but the patient refused any further therapy. The natural
      outcome of this neoplasm occurred with local recurrence and multiple metastases
      to the lungs, liver, and kidneys. CONCLUSIONS: MM should be included in the
      differential diagnosis of small-cell cutaneous tumor, and IHC is mandatory for
      diagnosis confirmation. The recommended suggested screening includes, as a
      minimum, one sensitive marker (S-100 protein) and one specific (HMB45) marker for
      melanogenesis.

PMID- 16089287
TI  - [Surgical correction of oroantral fistulas with integration of mandibular bone].
AB  - OBJECTIVE: The goal of this study was to formulate a proposal for an alternative
      surgical technique for treating >3 mm oroantral fistulas by integration of
      mandibular bone, in an attempt to decrease complications due to its invasive
      nature. MATERIAL AND METHODS: An observational, descriptive and longitudinal
      cohort study was carried out in the Maxillofacial Oral Surgery Department in the
      Specialty Hospital of the 21st Century National Medical Center of the Mexican
      Institute of Social Security in Mexico City. Sample patients with a diagnosis of
      oroantral fistula from January 1984 to December 1999 were selected. Surgical
      correction under general anesthesia was performed with the integration of
      mandibular osseous graft. Patients were followed postoperatively for 4 years.
      RESULTS: Of the 22 patients, 13 were male and 9 female, and all were between 25
      and 45 years old (average: 35.5 years). They were treated by application of
      osseous external mandible graft. In most cases, the graft was covered with a
      sliding mucoperiosteal flap, two were covered with a racquet-type flap and one
      only one procedure was Von Lagenbeck type because the nasal floor was involved.
      None of the patients refused the graft. All patients were followed
      postoperatively, both clinically and radiologically, for 4 years. DISCUSSION:
      Oroantral communication control is difficult because of mouth fluids, mixed
      bacterium and a humid environment that promotes development of infection.
      Therefore, the solution is complicated. As a consequence, it is thought that a
      simple technique such as the use of mandible graft, which offers advantages over
      others that are performed such as the application of calotte, rib, iliac crest,
      and perone grafts, but also implies double surgery in distant anatomic areas with
      particular complications in each one and a longer surgical time. CONCLUSIONS:
      Whatever the etiology of the oroantral communication, the fistulas must be
      treated immediately after diagnosis. Treatment protocol must be established
      according to the size and location and presence or absence of infectious process.
      Successful treatment is achieved by this process.

PMID- 16089288
TI  - [Training of family physicians and development of clinical aptitude].

PMID- 16089289
TI  - [Strategy of specialization in family medicine in the Mexican Institute of Social
      Security].
AB  - The main characteristics of the specialization course in Family Medicine given at
      the IMSS since March 2002 are described. We show the epistemological and
      methodological principles that support the plan of studies. The most important
      are a closer relationship between theory and practice, the development of
      clinical aptitudes through the study of problematic clinical cases, and
      methodological aptitudes such as the development of critical reading of
      theoretical texts and bibliographic and operative research. This continuing
      education strategy not only lowers the costs of formal education but also
      contributes to increasing the quality of medical care given at the first level
      family medical units.

PMID- 16089290
TI  - [The detection and cultivation of the scientific talent of young doctors].
AB  - Although science is not a key issue for the general public in The Netherlands,
      and scouting talents is not a customary activity, it is of the utmost importance
      for the scientific progress to detect gifted young people and to motivate them
      for a career in medical sciences. The scouting of talent should start as early as
      possible. A working group of the Royal Netherlands Academy of Arts and Sciences
      has issued a report on secondary schooling in which scouting of talent is a
      central issue. The modern medical curricula at the universities in The
      Netherlands all offer a substantial elective programme and the modern teaching in
      small groups also offers opportunities for teachers to detect talent. Recognition
      of scientific talent is further possible during the research period that every
      medical student has to go through. In Nijmegen, the Department of Internal
      Medicine organises a yearly master class at the end of the summer for the best
      second year medical students; in this course they are introduced to the
      scientific approach in medicine: from bedside to bench and vice versa. With this
      course we try to enforce the motivation for medical research. A prime instrument
      for the development of scientific talent is the nationally funded PhD track for
      medical specialists in training.

PMID- 16089291
TI  - [Scientific education in the training of specialists from the European
      perspective].
AB  - An overview is given on the scientific education of the Trainees (Specialists in
      Training in Europe). European legislation is clear and insists on the scientific
      formation in the undergraduate as well as in the Postgraduate education. It is
      the task of the national (or regional) authorities to create possibilities for
      research during clinical training. In most of the national training programmes
      Research activities are included. Moreover in the European visiting system
      Research facilities are an important item. Examples are shown how the Royal
      College of Obstetricians and Gynaecologists (U.K.) and the European Board and
      College of Obstetrics and Gynaecology have implemented these Research activities
      in the training programme.

PMID- 16089292
TI  - [Scientific education of the candidate specialist in training].
AB  - Scientific education is an essential component of the post-graduate training.
      Fluency in the language of sciences is necessary to understand scientific
      progress and to translate new scientific advances at the level of medical
      practice. To reach this goal, specific research skills and participation in
      research projects should be introduced in postgraduate training. Lack of
      dedicated time and interest are major barriers in implementing systematically
      research in the curricula. Some suggestions are made in order to improve research
      training in the postgraduate programs.

PMID- 16089293
TI  - [Aneurysms of the posterior cerebral artery: comparison of a retrospective series
      of surgically-treated patients with endovascularly-treated patients from the
      literature].
AB  - Subarachnoid hemorrhages caused by rupture of an aneurysm of the posterior
      cerebral artery are very rare. The surgical treatment of these aneurysms by
      clipping is studied in a retrospective series. Recent data from the literature
      seem to confirm good results when these aneurysms are treated by endovascular
      techniques. The results from the surgical series are compared with the results
      from the endovascular series. The endovascular treatment seems to become more
      important for the future.

PMID- 16089294
TI  - [The effect of interferon-gamma in collagen-induced arthritis in mice shows a
      mechanism of expanding Mac-1+ blood cells during its pathogenesis].
AB  - Collagen-induced arthritis (CIA) is an animal model for human rheumatoid
      arthritis. CIA is induced in the mouse by immunization with collagen type II in
      complete Freund's adjuvant (CFA). As a result of this immunization, mice will
      develop an autoimmune disease that is characterized by an inflammatory and
      destructive affection of the joints. IFN-gammaR KO mice have an increased
      susceptibility to CIA as compared to wild-type control animals: they developed
      arthritis with a significant earlier disease onset and a higher disease incidence
      and score. The results indicate that IFN-gamma acts as a disease-protective
      factor in CIA. The disease-protective effect of IFN-gamma in CIA appeared to be
      due to CFA that was used for the induction of CIA, and more precisely to the
      presence of killed mycobacteria in this adjuvant. The killed mycobacteria in CFA
      elicited in mice an extramedullar myelopoiesis and an expansion of Mac-1+ cells
      that was strongly inhibited by endogenous IFN-gamma. Parts of the expanded Mac-1+
      splenocytes were precursor cells for osteoclasts, they migrated to the joints
      after challenge with SDF-1, where they found to differentiate into mature
      osteoclasts who are responsible for bone destruction. The mechanism of expansion,
      migration and osteoclast activation occurred in IFN-gammaR KO as well as in wild
      type mice, but was much more pronounced in the mutant mice. Thus, the use of IFN
      gammaR KO mice has exposed a new mechanism in the pathogenesis of autoimmune
      arthritis in mice. These findings may have important clinical perspectives.

PMID- 16089295
TI  - [Orthodontics: interface between biology and biomechanics].
AB  - As far as craniofacial development is concerned, the orthodontist is mainly
      interested in growth of the jaws, craniofacial growth patterns and physiologic
      backgrounds of bone remodelling after tooth displacement. In biomechanics, the
      principle "action is equal to reaction" is one of the most important issues to
      deal with. The art in orthodontics is to distribute the reaction forces or to use
      them on purpose in an attempt to achieve one of the treatment goals. Reaction
      forces can be neutralized intra-orally. In this respect the location of the
      center of resistance of the tooth or a group of teeth needs to be defined
      carefully in order to have a good understanding of the biomechanical principles
      of tooth displacement. The action forces can be neutralized extra-orally. When no
      reaction forces on other teeth are applied, there will be no side effects of the
      reaction forces on other teeth. Research on the biomechanical principles of the
      headgear does offer some clinical information. Recently in orthodontics, the use
      of implants has been introduced. It can be used to neutralize reaction forces
      intra-orally. Moreover, the implants can be used primarily as anchorage during
      orthodontic tooth movement and later on to replace missing teeth. Recent animal
      studies at our department have shown that non-axial loading of implants with
      forces higher than 5 Newton can be used.

PMID- 16089296
TI  - [Indirect bronchial provocation tests: a new, specific group of bronchial
      provocation tests for asthma].
AB  - Asthma is characterized by a variable airway obstruction, bronchial
      hyperresponsiveness and airway inflammation. Usually, bronchial
      hyperresponsiveness is measured in the clinic by provocation with non specific
      stimuli such as histamine or methacholine. These stimuli are called direct, as
      they constrict the airways by a direct stimulation of airway smooth muscle.
      Pharmacological stimuli such as adenosine, tachykinins and bradykinin, and
      physical stimuli such as exercise, isocapnic hyperventilation or hypertonic
      saline, are called indirect stimuli: they stimulate inflammatory cells and/or
      neuronal cells and the released mediator and/or neurotransmitter causes the
      airways to narrow. In the past 10 years the mechanisms and receptors involved in
      the airway narrowing caused by these indirect bronchial challenges have been
      characterized. It has become clear that indirect challenges form a specific group
      of challenges that play a role in the diagnosis and the monitoring of asthma.

PMID- 16089297
TI  - FIP1L1-PDGFR alpha, a therapeutic target for the treatment of chronic
      eosinophilic leukemia.
AB  - The identification of the FIP1L1-PDGFRA fusion gene provides a molecular
      explanation for the pathogenesis of approximately half of the patients with the
      hypereosinophilic syndrome (HES). A diagnostic test to identify FIP1L1-PDGFRA
      positive HES cases (subsequently reclassified as chronic eosinophilic leukemia,
      CEL) is now available. FIP1L1-PDGFR alpha is a novel therapeutic target of the
      kinase inhibitor imatinib (Glivec, Novartis), which provides the basis for the
      treatment of these patients with this drug. FIP1L1-PDGFRA positive CEL patients
      respond very well to imatinib therapy, some of which are remarkable responses
      with normalization of the blood counts within 2 weeks after start of the therapy.
      Imatinib is well tolerated with minimal side effects, and most CEL patients
      respond to low doses of imatinib (100 mg/day), being important for lowering both
      the cost of therapy and drug related toxicity. All imatinib treated FIP1L1-PDGFRA
      positive CEL patients achieve hematological and cytogenetic remission, and the
      majority of patients also achieve a molecular remission with the fusion gene no
      longer detectable in blood, even by the most sensitive PCR techniques.

PMID- 16089298
TI  - Puncture of immature ovarian follicles in bovine assisted reproduction.
AB  - Transvaginal, ultrasound-guided follicular aspiration (OPU) is the method of
      choice to retrieve immature oocytes from highly valuable living donor cows for in
      vitro embryo production. In the introduction, we comment on general techniques of
      oocyte retrieval. In the second part, we describe the OPU technique from a
      technical point of view, and we discuss the factors that influence the quality
      and quantity of the oocytes retrieved. Firstly, there is a group of technical
      factors such as aspiration procedure, needle type, and the influence of the
      aspiration vacuum on cumulus oocyte complex morphology. Secondly, there is a huge
      group of biological influences, e.g. hormonal stimulation prior to follicle
      puncture, timing of the procedure relative to the estrous cycle, age, breed, and
      physiological condition of the donor. Subsequently, the use of OPU in combination
      with in vitro embryo production for the treatment of bovine sterility patients is
      discussed, as a way to obtain additional offspring from donors with impaired
      fertility. Reports on donor animal health and reproductive performance following
      repeated OPU are commented upon. Finally, future research possibilities related
      to the OPU technique are discussed. Additional gain is expected from the
      development of better ultrasound equipment, permitting optimal visualization of
      the smallest follicles. In addition, OPU equipment will be used for related
      purposes, such as repeated retrieval of ovarian biopsies, and the injection of
      local ovarian mediators, which will permit to study local paracrine hormonal
      effects, and their influence on oocyte quality.

PMID- 16089300
TI  - An improved scanning method based on characteristics of the human visual system
      for scanning electron microscopy.
AB  - An improved scanning method for the scanning electron microscope (SEM) is
      proposed. Here, quincuncial scanning (sampling) instead of a conventional
      (raster) scanning is used. This scanning method is very effective for quality
      improvement of an SEM image obtained under undersampling conditions (rough
      sampling). The present study focuses on characteristics of the human visual
      system, specifically the low response of eyes in diagonal directions. When using
      this method coupled with a high-precision interpolation, the number of pixels
      necessarily doubles. It is not surprising that it is advantageous for printing. A
      more important advantage is the fact that SEM images can be acquired with a
      shorter recording time. Hence, this type of scanning will be helpful for quick
      and frequent recordings in a "snapshot" mode, which up to now has not been
      achieved successfully by SEM.

PMID- 16089301
TI  - Characterization of an oil-degrading Microcoleus consortium by means of confocal
      scanning microscopy, scanning electron microscopy and transmission electron
      microscopy.
AB  - A consortium of microorganisms with the capacity to degrade crude oil has been
      characterized by means of confocal laser scanning microscopy (CLSM), transmission
      electron microscopy (TEM), and scanning electron microscopy (SEM). The analysis
      using CLSM shows that Microcoleus chthonoplastes is the dominant organism in the
      consortium. This cyanobacterium forms long filaments that group together in
      bundles inside a mucopolysaccharide sheath. Scanning electron microscopy and
      transmission electron microscopy have allowed us to demonstrate that this
      cyanobacterium forms a consortium primarily with three morphotypes of the
      heterotrophic microorganisms found in the Microcoleus chthonoplastes sheath. The
      optimal growth of Microcoleus consortium was obtained in presence of light and
      crude oil, and under anaerobic conditions. When grown in agar plate, only one
      type of colony (green and filamentous) was observed.

PMID- 16089302
TI  - Field-emission scanning electron microscopy analysis of morphology and enzyme
      distribution within an industrial biocatalytic particle.
AB  - Field-emission scanning electron microscopy (FESEM) was used in a technical
      feasibility study to obtain insight into the internal morphology and the
      intraparticle enzyme distribution of Assemblase, an industrial biocatalytic
      particle containing immobilized penicillin-G acylase. The results were compared
      with previous studies based on light and transmission electron microscopic
      techniques. The integrated FESEM approach yielded the same quantitative results
      as the microscopic techniques used previously. Given this technical equivalence,
      the integrated approach offers several advantages. First, the single preparation
      method and detection system avoids interpretation discrepancies between
      corresponding areas that were examined for different properties with different
      detection techniques in different samples. Second, the specimen size suitable for
      whole particle study is virtually unlimited, which simplifies sectioning and puts
      less stringent demands on the embedding technique. Furthermore, the sensitivity
      toward enzyme presence and distribution increases because the epitopes inside
      thick sections become available for labeling. Quick and unambiguous analysis of
      the relation between particle morphology and enzyme distribution is important
      because this information may be used in the future for the design of enzyme
      distributions in which the particle morphology can be used as a control
      parameter.

PMID- 16089305
TI  - Immunogold labeling of insulin growth factor-I receptors in elderly human
      skeletal muscle.
AB  - Age-associated muscle wasting, or sarcopenia, can be delayed or reversed with
      interventions, including exercise and pharmaceutical agents. Mapping morphometric
      changes in the skeletal muscle insulin growth factor 1 receptor can provide
      valuable information regarding mechanisms controlling muscle protein metabolism.
      Immunocolloidal gold labeling is a powerful immunocytochemistry procedure for
      detecting antigens at the ultrastructural level, providing plausible biological
      markers of cell and tissue adaptations to stimuli. The intent here was to employ
      immunogold labeling to identify, localize, and quantify the insulin growth factor
      receptor-I (IGF-IR) in elderly human skeletal muscle. Needle biopsy specimens of
      the leg vastus lateralis muscle were fixed with 1% glutaraldehyde and 4%
      paraformaldehyde, dehydrated, and embedded in LR white resin. Pilot experiments
      were carried out to establish optimal dilutions of primary and secondary
      antibodies and to employ controls to establish staining specificity. The 6 nm
      gold particles were first evident when viewed at transmission electron microscopy
      (TEM) magnifications at 54,000x and clearest at 71,000x. Consistencies were noted
      in the staining patterns, with the majority of particles lying in proximity to
      the myofilaments. Gold particles were also found randomly along the outer
      membrane of the sarcolemma and the mitochondrial membranes. National Institutes
      of Health (NIH) Image 1.55 version software was used to measure receptor density
      (NIH, Bethesda, Md., USA). It appears that immunogold labeling of postembedded
      tissue samples is a sensitive method for detecting IGF-I receptors at the
      ultrastructural level.

PMID- 16089306
TI  - Esophageal acid exposure in healthy adults in Taiwan: experience with pH step-up
      method by dual-channel pH-metry.
AB  - Esophageal acid exposure is common in normal subjects. The aim of this study was
      to investigate proximal and distal esophageal acid exposure in asymptomatic
      volunteers using dual-channel esophageal pH-metry with probe positioning by pH
      step-up. A total of 21 healthy subjects (9 male; mean age, 51 years) underwent 24
      hour ambulatory esophageal pH recording with the pH step-up method using a two
      channel pH probe, a portable digital data recorder, and computerized data
      analysis. All reflux episodes, episodes longer than 5 minutes, longest reflux
      episode, duration of acidity (pH <4), and percentage of time with acidity were
      analyzed. The 95th percentile for reflux parameters assessed in the
      distal/proximal esophagus were: total reflux episodes, 100/34; episodes greater
      than 5 minutes, 2.9/0; longest reflux episode, 16.6/2.95 minutes; duration of
      acidity, 87.95/15.5 minutes; and percentage of time with acidity, 7.0%/1.3%.
      Proximal and distal acid exposure were well correlated. Results showed that
      neither gender nor age influenced reflux parameters and that asymptomatic
      volunteers might experience some gastroesophageal reflux.

PMID- 16089307
TI  - Percutaneous ultrasound-guided radiofrequency ablation of intrahepatic
      cholangiocarcinoma.
AB  - This study evaluated the clinical applications, treatment effects, and
      complications of percutaneous ultrasound (US)-guided radiofrequency ablation
      (RFA) of intrahepatic cholangiocarcinoma. Ten patients (6 men and 4 women) with
      histologically proven cholangiocarcinoma underwent US-guided percutaneous RFA.
      Tumor diameters ranged from 1.9 to 6.8 cm. There were 12 sessions of RFA for 10
      solitary cholangiocarcinomas. Eight patients were treated at a single session and
      two patients had two treatment sessions. The efficacy of RFA was evaluated using
      contrast-enhanced dynamic computed tomography 1 month after treatment and then
      every 3 months. Complete necrosis was defined as lack of contrast enhancement of
      the treated region. There was complete necrosis in eight tumors. In two patients
      with large tumors (4.7 and 6.8 cm in diameter), enhancement of residual tissue
      was observed after RFA treatment, indicating residual tumor. Complete necrosis
      was seen in all five tumors (100%) with diameters of 3.0 cm or less, two of three
      tumors (67%) with diameters of 3.1-5.0 cm, and one of two tumors (50%) with
      diameters of more than 5.0 cm. A large biloma was found in one patient after
      treatment. No serious complications occurred in the other nine patients. In
      conclusion, percutaneous RFA is effective and successful in the treatment of
      intrahepatic cholangiocarcinoma of 3 cm or less and satisfactory for tumors of 3
      5 cm. The rate of serious complications after RFA is low. Further follow-up is
      necessary to determine long-term efficacy.

PMID- 16089308
TI  - T4 sympathectomy for palmar hyperhidrosis: an effective approach that
      simultaneously minimzes compensatory hyperhidrosis.
AB  - Compensatory hyperhidrosis (CH) is the most troublesome side effect after T2
      sympathectomy for palmar hyperhidrosis (PH). The aim of this study was to
      evaluate whether T4 ganglion interruption for PH is an effective approach that
      can simultaneously minimize the rate of CH. Between July 2001 and July 2003, 84
      PH patients undergoing bilateral thoracoscopic T4 sympathectomy were followed up
      in the outpatient clinic and by telephone questionnaire. Rates of success,
      regret, CH, recurrence, and complications were recorded. The follow-up period
      ranged from 18 to 42 months. All excessive hand sweating was stopped. Only two
      patients had mild CH that did not affect their daily activities. No patients had
      recurrence or regret. The only other complication was that four patients had
      postoperative minimal residual pneumothorax, which needed no treatment. All
      patients were satisfied with the outcome. T4 sympathectomy was an effective
      method to cure PH. The success rate was 100%. The rate of CH was remarkably low
      compared with T2 sympathetic ganglionic interruption.

PMID- 16089309
TI  - Assessing the psychometric and language equivalency of the Chinese versions of
      the Index of Nausea, Vomiting and Retching, and the Prenatal Self-Evaluation
      Questionnaire.
AB  - This study was an initial psychometric test of the Chinese versions of the Index
      of Nausea, Vomiting and Retching (INVR), and the Prenatal Self-Evaluation
      Questionnaire (PSEQ) in pregnant Taiwanese women. Although there already is
      evidence that the English-language versions of the scales are reliable and valid,
      it is important to verify the proper psychometric characteristics of the Chinese
      versions. Forward and backward translation, and a multiphase instrumentation
      study describing internal consistency, test-retest reliability, and content
      validity of the translated versions were conducted. A convenience sample was
      recruited from prenatal clinics in the south of Taiwan. Three measurement
      instruments were used in this study: the demographic inventory (DI), the INVR,
      and the PSEQ. Thirty pregnant women participated in the study. Both the internal
      consistency and stability coefficients of the INVR and PSEQ were satisfactory.
      The indices of content validity (CVI) for the Chinese versions of these two
      instruments were both 1.0, indicating that they are acceptable for use among
      Taiwanese pregnant women. This was the first instrumentation study of the INVR
      and PSEQ applied to Taiwanese pregnant women. Researchers could use this study as
      a model for future translation and application of psychometric instrumentation.

PMID- 16089310
TI  - Tuberculous pericardial abscess: a case report.
AB  - We present the case of a 71-year-old diabetic man who came to us complaining of
      dyspnea for 1 month. Chest X-ray showed cardiomegaly and bilateral pleural
      effusion. Echocardiography showed a pericardial cystic mass with external
      compression of the right ventricle. Because of clinically impending cardiac
      tamponade, we performed urgent sternotomy and removed the pericardial mass
      without event. Pathologic examination of the excised pericardial specimen showed
      caseous necrosis compatible with tuberculosis infection. The patient was put on a
      1-year treatment regimen of anti-tuberculosis medication. This case is an
      important reminder that tuberculosis can occur as a pericardial abscess.

PMID- 16089311
TI  - Citalopram-induced serotonin syndrome: a case report.
AB  - Serotonin syndrome is a disorder resulting from excess stimulation of serotonin
      and is associated with drug interaction, single-drug therapy, and overdose. We
      report a case involving a 32-year-old man who developed sudden agitation,
      diaphoresis, subjective fever, tremor, and insomnia. These symptoms were related
      to doubling the dose of citalopram in combination antidepressant therapy.
      Discontinuation of the agent resulted in early notable clinical resolution after
      1 week. This is a rare report of serotonin syndrome induced by citalopram
      polytherapy. Although serotonin syndrome is rare, clinicians need to recognize it
      early.

PMID- 16089312
TI  - Cutaneous metastasis from gastric adenocarcinoma: a case report.
AB  - Cutaneous metastasis from gastric adenocarcinoma is an infrequent disease entity.
      When present, it typically signifies disseminated disease with a poor prognosis.
      We report a case of a 57-year-old male patient with gastric cancer who developed
      generalized erythematous nodules on the chest, abdomen, back, neck, and four
      extremities 2 months postoperatively. Results of a skin biopsy disclosed groups
      of metastatic adenocarcinoma cells in the dermis and subcutaneous tissue, forming
      clusters and strands in a desmoplastic stroma. Histopathologic examination
      demonstrated that the cutaneous metastasis was of stomach origin.

PMID- 16089313
TI  - Facial cellulitis arising from dens evaginatus: a case report.
AB  - Dens evaginatus is a developmental anomaly that produces a tubercle on the
      occlusal surface of a tooth. It is found most frequently in the mandibular
      premolars. The occlusal tubercle easily causes occlusal interferences. Attrition
      or fracture of the tubercle can lead to pulpitis, pulp necrosis, periapical
      pathosis, and periapical infection. This case report illustrates the treatment of
      facial cellulitis arising from dens evaginatus with open apex. Calcium hydroxide
      was used for the apexification procedure. One year after canal obturation,
      radiography revealed no apical pathosis and the apical seal was evident.

PMID- 16089314
TI  - Harmonization of immunotoxicity guidelines in the ICH process--pathology
      considerations from the guideline Committee of the European Society of
      Toxicological Pathology (ESTP) .
AB  - As part of the ICH process of harmonization of testing guidelines for
      immunotoxicity, the European Society of Toxicologic Pathology (ESTP) has
      contributed to the scientific discussion on methods and evaluation of
      immunotoxicity studies with technical and scientific recommendations on
      toxicologic pathology. The weighing and sampling of immune organs is discussed
      taking into consideration specifically the value of lymph node weighing and the
      selection of appropriate lymph nodes for the detection of local and systemic
      effects. The different techniques of bone marrow preparation are considered for
      routine and extended investigations. Criteria are given for the gross and
      histopathological detection of effects in Peyer's patches. For the
      histopathological evaluation it is strongly recommended that each compartment
      within the different lymphoid organs is investigated separately and
      semiquantitatively since this approach has shown to increase the sensitivity and
      specificity of immunohistopathology.

PMID- 16089315
TI  - Neurogenic tumors in rats induced by ethylnitrosourea.
AB  - Ethylnitrosourea (ENU) was injected intravenously into Sprague-Dawley rats on day
      15 of gestation at doses of 0, 2.50, 6.25 and 10.00 mg/kg. The resulting 1980
      progeny were observed for up to 24 months in a life-time study (900 rats) or for
      periods of 171-325 days in a serial sacrifice study (1080 rats). The rats in both
      studies were randomized into three groups, one exposed to a radiofrequency, one
      sham-exposed and one cage control. Since no effects of the radiofrequency were
      observed on the ENU-induced tumors, the exposure groups were combined to
      facilitate study of the tumors by dose rate over time. All rats were necropsied
      and major organs were examined histologically including the brain, entire spinal
      cord, trigeminal nerves and all tumors. A total of 48 spinal cord tumors (SCT),
      251 spinal nerve tumors, 264 cranial nerve tumors and 1058 brain tumors were
      studied. The tumors were characterized by incidence, histologic type, volume,
      malignancy and multiplicity. Ethylnitrosouria, as given in this study, was
      determined to be an effective carcinogen reliably inducing (in order of
      frequency) brain, cranial nerve, spinal nerve and SCT. Dose of ENU correlated
      positively with the frequency, multiplicity, volume, malignancy, and negatively
      with latency of brain tumors and to a lesser extent with nerve tumors.

PMID- 16089316
TI  - Microarray analysis of T-2 toxin-induced liver, placenta and fetal liver lesions
      in pregnant rats.
AB  - Pregnant rats on day 13 of gestation were treated orally with 2 mg/kg of T-2
      toxin and sacrificed at 1, 3, 6, 9 and 12 h after the treatment (HAT).
      Histopathologically, the number of apoptotic cells was increased in the liver,
      placenta and fetal liver (peaked at 6, 12 and 9-12 HAT, respectively). To examine
      the gene expression profiles, we performed microarray analysis of these tissues
      at two selected time points based on the results of the TdT-mediated dUTP nick
      end labeling (TUNEL) staining. Increased expression of oxidative stress- and
      apoptosis-related genes was detected in the liver of dams, placenta and fetal
      liver of pregnant rats treated with T-2 toxin at the peak time point of
      apoptosis. Decreased expression of lipid metabolism- and drug-metabolizing enzyme
      related genes was also detected in these tissues. The results suggested that the
      mitogen-activated protein kinase (MAPK) pathway might be involved in the
      mechanism of T-2 toxin-induced apoptosis. In addition, increased expression of
      the c-jun gene was consistently observed in these tissues. Our results suggest
      that the mechanism of T-2 toxin-induced toxicity in pregnant rats is due to
      oxidative stress followed by the activation of the MAPK pathway, finally inducing
      apoptosis. The c-jun gene may play an important role in T-2 toxin-induced
      apoptosis.

PMID- 16089317
TI  - Histopathologic findings after treatment with different oxidosqualene cyclase
      (OSC) inhibitors in hamsters and dogs.
AB  - In order to investigate the toxicity of oxidosqualene cyclase (OSC) inhibitors,
      hamsters and dogs were treated up to 13 weeks with three different agents of this
      compound class. Subacute treatment (< or = 4 weeks) of hamsters and dogs with OSC
      inhibitors produced a similar spectrum of histopathologic lesions, which have
      previously been described for compounds of this pharmacological class. In the
      hamster, other lesions were produced only after subchronic treatment (13 weeks).
      After subacute treatment, histopathologic findings were observed in the eye, skin
      and forestomach. Lesions in the eye were characterized as proliferation, swelling
      and degeneration of lens fiber cells. This finding was considered to be an early
      stage in cataract development. In the skin and forestomach, squamous cell
      hyperplasia and hyperkeratosis accompanied by a mixed inflammation was observed.
      After subchronic treatment of hamsters, histopathologic findings were observed in
      the eye, skin, forestomach, testes, epididymides, prostate gland, seminal
      vesicles and long bones. Lesions in the eye were characterized as cataracts.
      Squamous cell hyperplasia accompanied by a diffuse hyperkeratosis and a mixed
      inflammation was seen in the skin and forestomach epithelium. In addition, testes
      lesions were characterized as testicular atrophy, generalized germ cell
      depletion, germ cell degeneration and tubular collapse. Atrophy, oligospermia and
      lumenal germ cells/cell debris were found in the epididymides. The prostate gland
      and seminal vesicles were decreased in size (atrophy). The bone lesions were
      characterized as a failure of enchondral ossification causing variable widening
      of the growth plate and a failure to form primary bone trabecula (lesions
      resemble those found in rickets). To our knowledge, this is the first study
      describing the toxicity of OSC inhibitors after subchronic treatment in hamsters
      and dogs. As all adverse effects described in this report are considered to be
      due to an exaggeration of the desired biochemical mechanism of action at high
      dose levels, a decrease of the systemic exposure by the use of more
      hepatoselective OSC inhibitors is expected to reduce the probability of these
      adverse effects in humans.

PMID- 16089318
TI  - L-selectin: adhesion, signalling and its importance in pathologic posttraumatic
      endotoxemia and non-septic inflammation.
AB  - The leucocyte expressed surface-bound L-selectin belongs to the selectin family
      of adhesion molecules. It exhibits adhesive as well as signalling functions.
      Mainly, it is of importance in lymphocyte homing and in the extravasation of
      leucocytes into the surrounding tissue during inflammation. Acting in the initial
      step of the cell adhesion cascade, L-selectin is responsible for the rolling of
      leucocytes on endothelial layers. Therefore, L-selectin is thought to be an
      adequate target for pharmacological interventions. Beneath the discussion of the
      molecules' general features like molecule structure and its regulation, the
      review focuses firstly on L-selectin in the context of posttraumatic inflammatory
      disorders, and secondly on the importance of L-selectin specific signalling
      events.

PMID- 16089319
TI  - The role of alkaloids in Ipomoea carnea toxicosis: a study in rats.
AB  - Ipomoea carnea promotes in livestock a toxicosis histologically characterized by
      vacuolated cells in different organs. The toxic principles of I. carnea are the
      alkaloids swainsonine and calystegines B1, B2, B3 and Cl. However, it has not
      been determined whether the effects observed in rats treated with this plant are
      only due to swainsonine or if the calystegines have some additive toxic effect.
      Thus, the aim of the present study was to evaluate in rats the toxic effects of
      the L carnea aqueous fraction (AF) and of its different alkaloids when
      administered individually at the same concentration as in this fraction, for 14
      days. No anorexic effect and/or alteration in body weight was observed in any
      group. The histopathologic study showed that while calystegines did not produce
      any toxic effects, swainsonine and I carnea AF promoted vacuolation in different
      organs, being more severe in the animals from the I. carnea AF group and
      extensible to other organs evaluated. No alterations were detected in the central
      nervous system of rats of any group assayed. The results obtained here suggest
      that calystegines may act as coadjuvants of swainsonine in I carnea toxicosis;
      however, little can be proposed about the neurotoxic effect of I. carnea since
      rats did not prove to be a good model for the reproduction of neuronal storage
      disease.

PMID- 16089320
TI  - Effect of sodium fluoride on gastric emptying and intestinal transit in mice.
AB  - Fluoride, a well-recognised harmful substance, is easily absorbed by the
      gastrointestinal mucosa. It is therefore conceivable that any alteration of the
      gastrointestinal motility can affect the rate of absorption of fluoride and leads
      to aggravation of its toxic effects. The effects of fluoride on gastric emptying
      and intestinal transit were studied in the mouse using a carboxymethyl cellulose
      (CMC) solution as a non-nutrient meal. The participation of the cholinergic and
      nitrergic systems in these effects was also evaluated. Oral gavage of 5 mM NaF
      had no significant effect on gastric emptying and intestinal transit of the CMC
      meal, whereas a decrease of gastric emptying (-33%, P<0.05) and an increase in
      intestinal transit (+20.7%, P<0.05) were observed with 20 mM NaF. Atropine
      injection induced a significant decrease of gastric emptying. Combined treatment
      of atropine with 20 mM NaF brought about a further, but not significant decrease
      in gastric emptying. N-G-nitro-L-arginine-methyl ester (L-NAME) treatment with or
      without oral administration of NaF decreased gastric emptying. Atropine treatment
      significantly depressed intestinal transit from 56.5% to 37.7% in the absence of
      NaF and from 70.1% to 42.8% in its presence. In contrast, L-NAME administration
      either alone or with fluoride increased intestinal transit (P<0.05). The present
      results suggest that fluoride alter gastrointestinal motility, an effect that may
      partly involve the cholinergic pathway.

PMID- 16089321
TI  - Dietary supplementation with monounsaturated and long-chain polyunsaturated fatty
      acids influences the liver structural recovery and hepatocyte binuclearity in
      female Wistar rats in experimental cirrhosis induced by thioacetamide.
AB  - Oral administration of 300 mg/l thioacetamide (TAA) for 4 months causes hepatic
      lesions comparable to those described in alcoholic liver cirrhosis in humans and
      associated protein-energy malnutrition. In this sense, direct supplementation
      with monounsaturated fatty acids (MUFAs) and/or polyunsaturated fatty acids
      (PUFAs) might provide an advantage in the correction of the fatty acid deficiency
      in these patients. PUFAs are essential components of cell membranes maintaining
      its fluidity and function, important energy sources, and precursors of
      eicosanoids. Moreover, these fatty acids also modulate gene transcription, mRNA
      stability, and cellular differentiation. METHODS: Fifty-four female Wistar rats
      (Interfauna Iberica, Barcelona, Spain) weighing 110-120 g were used in this
      study. The animals were divided into two groups: one group was treated with 300
      mg/l TAA dissolved in drinking water during 4 months, and the other group, which
      served as a control, was given water without TAA. To evaluate the changes induced
      by the administration of TAA for 4 months, TAA-treated (n = 7) and control
      animals (n = 5) were killed. Then, the TAA treatment was stopped and the rest of
      the animals in both TAA and control groups were divided into three experimental
      groups and three control groups which received for 2 weeks different type of
      diets. Using the TAA-induced liver cirrhosis model in rats, we analysed the
      effects of dietary supplementation with MUFAs and PUFAs on binuclearity and
      ultrastructure of hepatocytes. After TAA-induced cirrhosis, we analysed whether
      dietary supplementation with fatty acids may restore the normal percentage of
      binucleated cells, as well as the ultrastructure, nuclear area, and
      nuclear/cytoplasm index of hepatocytes. RESULTS: Treatment with TAA causes
      cirrhosis characterized by the appearance of parenchyma nodules and fibrous
      septae, as well as qualitative and quantitative alterations in liver and plasma
      lipids. Our results indicate that dietary MUFAs support hepatocyte recovery
      regarding its ultrastructural and morphometric values. However, PUFAs-enriched
      diets (n-3 and n-3 + n-6) do not correct hepatomegaly, fibrosis or lipid
      accumulation. Thus, dietary PUFAs do not enhance hepatocyte recovery from
      morphological and ultrastructural alterations. CONCLUSIONS: In our experimental
      model of cirrhosis, dietary supplementation with a high proportion of long-chain
      PUFAs (n-3 or n-6) negatively influences liver recovery. This negative effect was
      likely due to the increased susceptibility of cell membranes to lipid
      peroxidation, together with an alteration in lipid metabolism.

PMID- 16089322
TI  - Multinucleate cells (MNC) as sensitive semiquantitative biomarkers of the toxic
      effect after experimental fibrous dust and cigarette smoke inhalation by rats.
AB  - Changes in the counts of binucleate (BNC) and multinucleate cells (MNC) in cell
      mixtures from lung tissue and bronchoalveolar lavage fluid (BALF) as well as in
      proportions of four types of BALF cells: Alveolar macrophages (AM), lymphocytes,
      polymorphonuclears (PMN), BNC and in total BALF protein were followed in a study
      comparing the toxicity of wollastonite with that of amosite asbestos in Fischer
      344 rats. Both of the fibrous dusts were inhaled every second day at 30 or 60
      mg/m3 air combined with daily exposure to cigarette smoke at 30 mg of total
      particulate matter (TPM)/m3 air for 1 h. The exposures lasted 175 days. Both,
      proportions of BNC as well as of MNC in lung cell mixtures rose significantly
      after exposure to cigarette smoke only. After inhalation of wollastonite the BNC
      proportions in all except the lower dust exposure group compared to controls
      showed a significant rise with the maximal factor value of 2.1 in the higher dust
      plus smoke exposure group. Wollastonite caused only marginal changes in MNC and
      other inflammation parameters. After inhalation of amosite at comparing to
      controls the proportion of BNC rose 8 times in the 30 mg/m3 and 11 times in the
      60 mg/m3 exposure group, respectively. The effect of smoking was additive. The
      proportions of MNC were 39 times higher in the 30 mg/m3 and 41 times higher in
      the 60 mg/m3 amosite exposure group than in controls. In the higher exposure
      group the effect of smoking was synergic in that the MNC proportion rose about 58
      times over control values from 0.05% up to about 3.0% (99% confidence interval-
      CI = 2.7-3.3%). The other followed inflammation parameters showed the presence of
      inflammation in the lung. It could be concluded that wollastonite at the same
      inhalation exposure concentration caused in rats less toxic effects than amosite,
      and, that the number of MNC, as well as BNC in lung cell mixtures and in BALF may
      serve as an important semiquantitative biomarker of inflammation.

PMID- 16089323
TI  - Joint effects of acetochlor and urea on germinating characteristics of crop
      seeds.
AB  - In order to evaluate ecological risk of agrochemicals in common use, joint toxic
      effects of acetochlor and urea on germinating characteristics of Chinese cabbage
      (Brassica Pekinensis Rupr) seeds were investigated using the water-culture method
      and the soil-culture method. The results indicated that excessive application of
      acetochlor and urea, when the concentrations were higher than 31.3 mg x kg(-1)
      for acetochlor and 500 mg x kg(-1) for urea, had strong inhibitory effects on the
      rate of seed germination, root elongation and hypocotyl length of Chinese
      cabbage. The inhibitory rate of the germinating characteristics of Chinese
      cabbage seeds was significantly increased with an increase in the concentration
      of acetochlor or urea. The two agrochemicals in water had a stronger toxicity
      than these in the soil at the same concentration. Among the three indexes,
      hypocotyl length was the most sensitive to the toxicity of acetochlor and urea.

PMID- 16089324
TI  - Evaluation of genotoxicity of combined soil pollution by cadmium and
      imidacloprid.
AB  - Cadmium (Cd) is one of the important pollutants of soil and the genotoxicity of
      Cd-contaminated soil was studied in combination with imidacloprid. The single
      cell gel electrophoresis or comet assay was used to quantify DNA strand breaks as
      a measure of DNA damage induced by Cd and imidacloprid contamination in soil. The
      soil was artificially contaminated by Cd (0.0, 0.2, 0.5, 1.0, 2.0 mg x kg(-1) dry
      soil) or Cd (0.0, 0.2, 0.5, 1.0, 2.0 mg x kg(-1) dry soil) and imidacloprid (0.5
      mg x kg(-1) dry soil). Roots of Vicia faba were exposed to the contaminated soil
      for 2 h at 25 degrees C and were used in the comet assay. DNA damage was measured
      as the values of percentage of nuclei with tails, tail length, tail DNA, tail
      moment (TM), and Olive tail moment (OTM). DNA damages of root tips of Vicia faba
      increased after Cd treatment and there were dose-related increases in DNA damage
      measured as these parameters. However, the addition of imidacloprid further
      increased the DNA damage. These data confirmed the genotoxic effect of Cd to
      plants, and that the combined pollution with imidacloprid can enhance the
      genotoxicity of Cd.

PMID- 16089325
TI  - Impacts of methamidophos, copper, and their combinations on bacterial community
      structure and function in black soil.
AB  - The potential ecotoxicologial risks of methamidophos, copper, and their
      combinations on microbial community of black soil ecosystem in the Northeast
      China were assessed in species richness and structures by using 16S rDNA-PCR-DGGE
      analysis approach, and functional characteristics at community levels by using
      BIOLOG(GN) system analysis method as well as two conventional methods (DHA and
      SIR). All results of DGGE banding fingerprint patterns (amplified by bacterial
      specific 16S rDNA V3 high variable region universal primer) indicated that the
      species richness of bacterial community in tested soil was significantly
      decreased to different extents by using different concentrations of single
      methamidophos, copper, especially some of their combinations had worse effects
      than their corresponding single factors. In addition, the structures of soil
      bacterial community had been disturbed under all stresses applied in this study
      because of the enrichment of some species and the disappearance of other species
      from the bacterial community. The effects of the single factors with lower
      concentrations on the community structure were weaker than those with higher
      concentrations. Moreover, the bacterial community structures under the combined
      stresses of methamidophos and copper were significantly different from those of
      control and their corresponding single factors. The change of DHA and carbon
      source substrate utilizing fingerprint patterns based on BIOLOG(GN) system were
      two relatively sensitive directors corresponding to the stress presented in this
      study. Between methamodophos and copper, there happened the significant joint
      toxic actions when they were used in combination on DHA and carbon source
      substrate utilizing fingerprint patterns of soil bacterial communities. The DHA
      of soil under the combined stresses was lower than that of the control and that
      under the single factors, and the BIOLOG(GN) substrate utilizing patterns of soil
      treated by combinations were distinctively differentiated from the control and
      their corresponding single factors. From all of above, the methamidophos, copper,
      especially their combinations had the clearly potential ecotoxicological risks to
      influence the natural soil microbial ecological system by changing the structure,
      richness, and the functional characteristics of microbial community.

PMID- 16089326
TI  - Effects of slow-release urea fertilizers on urease activity, microbial biomass,
      and nematode communities in an aquic brown soil.
AB  - A field experiment was carried out at the Shenyang Experimental Station of
      Ecology (CAS) in order to study the effects of slow-release urea fertilizers high
      polymer-coated urea (SRU1), SRU1 mixed with dicyandiamide DCD (SRU2), and SRU1
      mixed with calcium carbide CaC2 (SRU3) on urease activity, microbial biomass C
      and N, and nematode communities in an aquic brown soil during the maize growth
      period. The results demonstrated that the application of slow-release urea
      fertilizers inhibits soil urease activity and increases the soil NH4+-N content.
      Soil available N increment could promote its immobilization by microorganisms.
      Determination of soil microbial biomass N indicated that a combined application
      of coated urea and nitrification inhibitors increased the soil active N pool. The
      population of predators/omnivores indicated that treatment with SRU2 could
      provide enough soil NH4+-N to promote maize growth and increased the food
      resource for the soil fauna compared with the other treatments.

PMID- 16089327
TI  - Short-term toxic effects of chlorobenzenes on broadbean (Vicia faba) seedlings.
AB  - The root growth, changes in superoxide dismutase (SOD, EC 1.15.1.1) activity,
      malonyldialdehyde (MDA) and total soluble protein level of broadbean (Vicia faba)
      seedlings were researched at different soil concentrations of chlorobenzene (CB),
      1,2,4-trichlorobenzene (TCB) and hexachlorobenzene (HCB). The results showed that
      root growth of seedlings was interrupted after 5 d of 50-200 microg x g(-1) TCB
      treatment. During a 3 d recovery period, root growth was, however, restored to
      some extent although there was a delay in returning to the control level. The
      total soluble protein content in seedlings increased with TCB concentration and
      duration of exposure. Effect of TCB stress on SOD activity in seedlings displayed
      a significant dose-effect relationship for 1-5 d of 50-200 microg x g(-1)
      treatment. When broadbean seedlings were placed in clean tap water for 3 d
      following exposure to 5 d of TCB stress to clear tap water for 3 d, SOD activity
      at 50 microg x g(-1) TCB recovered towards control level (P>0.05) while a
      significant increase in SOD activity was observed at 100 and 200 microg x g(-1)
      TCB compared to control (P<0.05). The experiments also revealed that a
      significant increase of MDA level in seedlings occurred after 3 and 5 d of 100
      and 200 microg x g(-1) TCB treatment (P<0.05 and P<0.01), and there was a
      positive correlation between TCB concentration and MDA level. All the above
      results showed that SOD activity and MDA level of broadbean seedlings might be
      proposed as the biomarkers for short-term TCB contamination in soil. Compared to
      TCB, the toxicity of 50-1000 microg x g(-1) CB or HCB in soil to broadbean
      seedlings was not observed after a 3 d exposure.

PMID- 16089328
TI  - DNA damaging effects of carbofuran and its main metabolites on mice by
      micronucleus test and single cell gel electrophoresis.
AB  - The DNA damaging effects of the carbamate pesticide carbofuran and its four
      metabolites (carbofuranphenol, 3-ketocarbofuran, 3-hydrocarbofuran and
      nitrosocarbofuran) on mice were evaluated by single cell gel electrophoresis
      (SCGE) assay and micronucleus test. KM mice were exposed to test compounds with
      different doses of 0.1, 0.2 and 0.4 mg/kg through intraperitoneal injection two
      times with an internal of 24 h, and then killed by cervical dislocation 6 h after
      the second injection. In SCGE assay, isolated mice peripheral blood lymphocytes
      were employed to determine DNA damaging degree after a 1 h treatment by test
      compounds and a following electrophoresis. Carbofuran and carbofuranphenol showed
      negative results in both test and had no obvious toxicity. 3-Hydrocarbofuran and
      nitrosocarbofuran were positive. 3-Ketocarbofuran could not induce micronucleus
      formation but caused significant DNA migration in SCGE test. These tests revealed
      that 3-ketocarbofuran, 3-hydrocarbofuran and nitrosocarbofuran are potential
      mutagesis and further research is needed.

PMID- 16089329
TI  - Ecotoxicity of soils contaminated with industrial and domestic wastewater in
      western Shenyang, China.
AB  - Soil samples were collected from 7 sites in the up-, mid- and down-reach along
      and nearby the wastewater irrigation channel, western Shenyang of China. The
      concentrations of selected pollutants (mineral oil, PAHs--polycycle aromatic
      hydrocarbons and Cd) were determined by UV spectrometer, HPLC and AAS (atomic
      adsorption spectrometer) spectrometer, respectively. Toxicity effects of soils
      were evaluated by seedling emergence test with root length of wheat as the end
      point and by earthworms test with the mortality rate and inhibition rates of body
      weight as endpoints. Results showed accumulation of pollutants for most soils
      with concentration of 200.2 mg x kg(-1)-1600 mg x kg(-1) for mineral oil, 0.33 mg
      x kg(-1)-1.81 mg x kg(-1) for Cd and 900.16 mg x kg(-1)-2737.91 mg x kg(-1) for
      PAHs. The inhibition rates of root elongation were from -20% up to 40%, and
      mortality rates of earthworms ranged from 0%-40% from the exposure period of two
      weeks to eight weeks by sampling interval of two weeks, the inhibition rates of
      earthworm growth were from -19.36% to 34.53%, showing effects of stimulation at 2
      weeks to an increasing effects of inhibition at 4, 6 and 8 weeks, respectively.
      Mortality rates correlated with the loss of body weight of earthworms. This study
      indicated the potential risk of pollutants of environmental low content in soil
      by the determination of selected chemicals combined with toxicity indexes.

PMID- 16089330
TI  - Effects of dissolved organic matter from sewage sludge on the atrazine sorption
      by soils.
AB  - The effects of dissolved organic matter (DOM), water soluble organic matter
      derived from sewage sludge, on the sorption of atrazine (2-chloro-4-ethylamino-6
      isopropylamino-1,3,5-trazine) by soils were studied using a batch equilibrium
      technique. Six paddy soils, chosen so as to have different organic carbon
      contents, were experimented in this investigation. Atrazine sorption isotherms on
      soils were described by the linear equation, and the distribution coefficients
      without DOM (Kd) or with DOM (Kd*) were obtained. Generally, the values of Kd*/Kd
      initially increased and decreased thereafter with increasing DOM concentrations
      of 0-60 mg DOC x L(-1) in soil-solution system form. Critical concentrations of
      DOM (DOM(np)) were obtained where the value of Kd* was equal to Kd. The presence
      of DOM with concentrations lower than DOM(np) promoted atrazine sorption on soils
      (Kd* > Kd), whereas the presence of DOM with concentrations higher than DOM(np)
      tended to inhibit atrazine sorption (Kd* < Kd). Interestingly, DOM(np) for tested
      soils was negatively correlated to the soil organic carbon content, and the
      maximum of Kd*/Kd (i.e. Kmax) correlated positively with the maximum of DOM
      sorption on soil (Xmax). Further investigations showed that the presence of
      hydrophobic fraction of DOM evidently promoted the atrazine sorption on soils,
      whereas the presence of hydrophilic DOM fraction obviously tended to inhibit the
      atrazine sorption. Interactions of soil surfaces with DOM and its fractions were
      suggested to be the major processes determining atrazine sorption on soils. The
      results of this work provide a reference to the agricultural use of organic
      amendment such as sewage sludge for improving the availability of atrazine in
      soils.

PMID- 16089331
TI  - Effects of methamidophos and glyphosate on copper sorption-desorption behavior in
      soils.
AB  - A batch-equilibration technique was employed to study the impact of two
      organophosphorus pesticides methamidophos (MDP) and glyphosate (GPS) on copper
      (Cu2+) sorption-desorption for phaeozem and burozem collected from Northeastern
      China. The addition of the two pesticides decreased Cu2+ sorption, increased Cu2+
      desorption and prolonged the equilibrium time of Cu2+ sorption-desorption. But
      GPS appeared to exert a stronger influence on Cu2+ sorption-desorption due to its
      stronger complexion with Cu2+. When MDP was added, Cu2+ sorption-desorption was
      linearly correlated with MDP treatment concentrations. But in the presence of
      GPS, Cu2+ sorption first underwent a rapid decrease period, and then slowly
      tended towards a steady period. The reverse pattern could be found for Cu2+
      desorption in the presence of GPS. Without pesticides and with the existence of
      MDP, Cu2+ sorption-desorption kinetics was well conformed to two-constant
      equation and Elovich equation. But that was not the case for Cu2+ desorption
      kinetics in the presence of GPS although its sorption could be also described by
      these two equations.

PMID- 16089332
TI  - Correlations between the ages of Alnus host species and the genetic diversity of
      associated endosymbiotic Frankia strains from nodules.
AB  - Nodule samples were collected from four alder species: Alnus nepalensis, A.
      sibirica, A. tinctoria and A. mandshurica growing in different environments on
      Gaoligong Mountains, Yunnan Province of Southwest China and on Changbai
      Mountains, Jilin Province of Northeast China. PCR-RFLP analysis of the IGS
      between nifD and nifK genes was directly applied to uncultured Frankia strains in
      the nodules. A total of 21 restriction patterns were obtained. The Frankia
      population in the nodules of A. nepalensis had the highest genetic diversity
      among all four Frankia populations; by contrast, the population in the nodules of
      A. mandshurica had the lowest degree of divergence; the ones in the nodules of A.
      sibirica and A. tinctoria were intermediate. A dendrogram, which was constructed
      based on the genetic distance between the restriction patterns, indicated that
      Frankia strains from A. sibirica and A. tinctoria had a close genetic
      relationship. Frankia strains from A. nepalensis might be the ancestor of Frankia
      strains infecting other Alnus species. From these results and the inference of
      the ages of Alnus host species, it is deduced that there was a co-evolution
      between Alnus and its microsymbiont Frankia in China.

PMID- 16089333
TI  - Spatial heterogeneity of DTPA-extractable zinc in cultivated soils induced by
      city pollution and land use.
AB  - The spatial heterogeneity of DTPA-extractable zinc in the cultivated soils of
      Shenyang suburbs in Liaoning Province of China was investigated, and its map was
      drawn by the methods of geostatistics combined with geographic information
      system. The data of soil DTPA-extractable zinc fitted normal distribution after
      logarithm transformation, and its semivariogram fitted a spherical model. The
      semivariogram indicated that the spatial dependence of soil DTPA-extractable zinc
      content was moderate, with the spatial dependence range of 1.69 km and the
      fractal dimension of 1.96. Stochastic factors contributed to 49.9% of the spatial
      variability, while structural factors contributed to 50.1% of it. The spatial
      heterogeneity of soil DTPA-extractable zinc shown by a kriged interpolation map
      was deeply influenced by stochastic factors such as city pollution, land use
      pattern and crop distributions. For example, the average content of Zn in
      vegetable garden soils was 2.5-4 times as much as in their originated soils, and
      was lower in paddy soils than in their originated soils. The areas with a higher
      content of soil DTPA-extractable zinc appeared in the near suburbs and the
      riverside along Hunhe River and the wastewater drainage of Xihe River, and the
      extremely high values in the near suburb of the city's residential area were a
      striking feature, indicating the key role of city pollution in the spatial
      heterogeneity of soil DTPA-extractable zinc. When recorded in the form of a soil
      pollution map, the results of such a survey make it possible to identify the
      unusually polluted areas, and to provide more information for precise agriculture
      and environmental control.

PMID- 16089334
TI  - Initial results for urban metal distributions in house dusts of Syracuse, New
      York, USA.
AB  - A program of house dust sample collection and analysis has begun in Syracuse, New
      York, USA, in order to determine the feasibility of a geography-based exposure
      assessment for urban metals. The sampling program, and the protocols it employs,
      is described for two different types of wipe media, Ghost Wipes and Whatman
      Filters. Preliminary results show that strong spatial patterns of floor dust
      loading (mg dust per square foot) can be observed for data aggregated at a
      spatial scale of about 1600 m (approximately 2.5 km2). Floor dust metal
      concentrations were similar to those found in other urban environments, with some
      regional variation. The median floor dust Pb concentration was approximately 108
      mg x kg(-1) for this initial data set of approximately 264 sampled residential
      locations, and varied from 50 to 1100 mg Pb x kg(-1).

PMID- 16089335
TI  - A water quality analysis system to evaluate the impact of agricultural activities
      on N outflow in river basins in Japan.
AB  - We have developed a personal-computer-based water quality analysis system for
      river basins. The system estimates potential N outflow by model and calculates
      actual N outflow from monitoring data. For the former it uses the potential load
      factor method to estimate annual nitrogen load from various sources and runoff
      potential from each area of land in a basin. For the latter it analyzes water
      quality monitoring data in relation to meteorological data. We used the system to
      analyze N outflow in basins around Lake Kasumigaura and the Yahagi River in
      central Honshu, Japan. The land around Lake Kasumigaura is rather flat, and about
      25% is periodically flooded for rice and lotus cultivation. The land around the
      Yahagi River is mountainous, and much less land is flooded. In the Yahagi River
      basin the actual N outflow agreed closely with the potential. However, the actual
      N outflow in the basin around Lake Kasumigaura was much less than the potential,
      suggesting that a large part of the N load is denitrified in flooded soils. This
      further indicates that a sequence of different land uses including flooded rice
      fields is an important factor determining N outflow in basins in Japan. On the
      basis of the above analyses, we incorporated a denitrification model into the
      system that enables us to estimate N balance in a designated basin; this system
      may be helpful in the formulation of scenarios of land use and soil management
      for improving water quality.

PMID- 16089336
TI  - Trace metals in barnacles: the significance of trophic transfer.
AB  - Barnacles have very high accumulated trace metal body concentrations that vary
      with local trace metal bioavailabilities and represent integrated measures of the
      supply of bioavailable metals. Pioneering work in Chinese waters in Hong Kong
      highlighted the potential value of barnacles (particularly Balanus amphitrite) as
      trace metal biomonitors in coastal waters, identifying differences in local trace
      metal bioavailabilities over space and time. Work in Hong Kong has also shown
      that although barnacles have very high rates of trace metal uptake from solution,
      they also have very high trace metal assimilation efficiencies from the diet.
      High assimilation efficiencies coupled with high ingestion rates ensure that
      trophic uptake is by far the dominant trace metal uptake route in barnacles, as
      verified for cadmium and zinc. Kinetic modelling has shown that low efflux rate
      constants and high uptake rates from the diet combine to bring about accumulated
      trace metal concentrations in barnacles that are amongst the highest known in
      marine invertebrates.

PMID- 16089337
TI  - Quantifying effects of soil heterogeneity on groundwater pollution at four sites
      in USA.
AB  - Four sites located in the north-eastern region of the United States of America
      have been chosen to investigate the impacts of soil heterogeneity in the
      transport of solutes (bromide and chloride) through the vadose zone (the zone in
      the soil that lies below the root zone and above the permanent saturated
      groundwater). A recently proposed mathematical model based on the cumulative beta
      distribution has been deployed to compare and contrast the regions' heterogeneity
      from multiple sample percolation experiments. Significant differences in patterns
      of solute leaching were observed even over a small spatial scale, indicating that
      traditional sampling methods for solute transport, for example the gravity pan or
      suction lysimeters, or more recent inventions such as the multiple sample
      percolation systems may not be effective in estimating solute fluxes in soils
      when a significant degree of soil heterogeneity is present. Consequently,
      ignoring soil heterogeneity in solute transport studies will likely result in
      under- or overprediction of leached fluxes and potentially lead to serious
      pollution of soils and/or groundwater. The cumulative beta distribution technique
      is found to be a versatile and simple technique of gaining valuable information
      regarding soil heterogeneity effects on solute transport. It is also an excellent
      tool for guiding future decisions of experimental designs particularly in regard
      to the number of samples within one site and the number of sampling locations
      between sites required to obtain a representative estimate of field solute or
      drainage flux.

PMID- 16089338
TI  - Study of microbial community structures in UASB sludge treating municipal
      wastewater by denaturing gradient gel electrophoresis of 16S rDNA.
AB  - The structures of microbial communities in lab-scale upflow anaerobic sludge
      blanket (UASB) reactors for treating municipal wastewater with different ratios
      of COD soluble/COD total were studied using denaturing gradient gel
      electrophoresis (DGGE) of 16S rRNA genes. The microbial structure of the inoculum
      sludge obtained from a full-scale UASB reactor of treating potato processing
      wastewater was compared with the structures of sludges collected from three lab
      scale UASB reactors after eight months feeding with raw municipal wastewater,
      with CEPS (chemically enhanced primary sedimentation) pretreated municipal
      wastewater, and with a synthetic municipal sewage, respectively. Computer-aided
      numerical analysis of the DGGE fingerprints showed that the bacterial community
      underwent major changes. The sludges for treating raw and CEPS pretreated
      wastewater had very similar bacterial and archaeal communities (82% and 96%
      similarity) but were different from that for treating the synthetic sewage.
      Hence, despite similar % COD in the particulate form in the synthetic and the
      real wastewater, the two wastewaters were selected for different microbial
      communities. Prominent DGGE bands of Bacteria and Archaea were purified and
      sequenced. The 16S rRNA gene sequences of the dominant archaeal bands found in
      the inoculum, and UASB sludge fed with raw sewage, CEPS pretreated wastewater,
      and synthetic sewage were closely associated with Methanosaeta concilii. In the
      UASB sludge fed with synthetic sewage, another dominant band associated with an
      uncultured archaeon 39-2 was found together with M. concilii.

PMID- 16089339
TI  - Respective and interactive effects of doubled CO2 and O3 concentration on
      membrane lipid peroxidation and antioxidative ability of soybean.
AB  - Effects of doubled CO2 and O3 concentration on Soybean were studied in open-top
      chambers (OTC). Under doubled CO2 concentration, grain yield and biomass
      increased, the SOD activity, vitamin C (Vc) and carotenoid (Car) content also
      increased; Superoxide (O2-*) generating rate decreased, relative conductivity and
      malondialdehyde (MDA) content significantly declined. But under doubled O3
      concentration, the SOD activity, Vc and Car contents declined, resulting in
      imbalance of activated-oxygen production, enhanced O2-* generating rate and
      accelerated process of lipid peroxidation and increase in MDA content and ion
      leakage of leaves. The final result was decreased grain yield and plant biomass.
      Interactive effects of doubled CO2 and O3 concentrations on soybean were mostly
      counteractive. However, the beneficial effects of concentration-doubled CO2 more
      than compensate the negative effects imposed by doubled O3, and the latter in its
      turn partly counteracted the positive effects of the former.

PMID- 16089340
TI  - Phyto-availability and speciation change of heavy metals in soils amended with
      lignin as micro-fertilizer.
AB  - Lignin is a primary byproduct from the black liquor treatment in paper making
      industries, its application as micro-fertilizer in agricultural land might
      provide a promising alternative to sewage discharge. However, application of such
      a micro-fertilizer might affect the soil properties and result in soil pollution.
      In this study, the effects of lignin application on phyto-availability and
      speciation change of heavy metals in soils were investigated. Greenhouse
      experiments showed that lignin application improved the growth of winter wheat
      (Triticum aestivum L.) in all three soils investigated. The increase of the
      biomass for wheat shoot was 59.7%, 39.8% and 12.3% for Beijing soil, Jiangxi soil
      and Dongbei soil, respectively. In contrast, lignin amendment decreased the
      concentrations of heavy metals in wheat shoots from 2.2% to 61.0%. Sequential
      extraction procedure of a three-step BCR was used to investigate the fraction
      distribution. The extractable fractions were specified as fraction B1: water
      soluble, exchangeable and carbonate bound or weakly specifically adsorbed; B2: Fe
      Mn oxide bound; B3: organic matter and sulfide bound. The results showed that
      lignin application led to the redistribution of heavy metals in each fraction.
      Generally, heavy metals decreased in B1 and B2 fractions and increased in B3
      fraction. Upon the results short-term application of lignin in agricultural land
      not only improves the growth of wheat but also reduces the phyto-abailability of
      heavy metal in wheat.

PMID- 16089341
TI  - Study of the tolerance of Hippochaete ramosissimum to Cu stress.
AB  - We investigated the tolerance of Hippochaete ramosissimum and the changes in
      physiological metabolism following exposure to copper using pot experiments and
      analyzing plant physiology and biochemistry. The results showed that Cu tolerance
      in Hippochaete ramosissimum varied significantly between different populations;
      the tolerance of plants living in Cu polluted areas for extended periods of time
      exceeded that of plants living in unpolluted areas. SOD and POD activities in
      highly Cu tolerant plants increased noticeably following exposure to Cu. This
      indicates that maintaining and increasing the two kinds of protective enzyme
      activities are the primary foundations of plant tolerance. However, no change in
      CAT activity was demonstrated following Cu exposure. In summary, there existed
      considerable differences in physiological metabolism between different
      populationsof Hippochaete ramosissimum following exposure to Cu.

PMID- 16089342
TI  - Metal concentrations and mycorrhizal status of plants colonizing copper mine
      tailings: potential for revegetation.
AB  - A field survey of metal concentrations and mycorrhizal status of plants growing
      on copper mine tailings was conducted in Anhui Province, China. Available
      phosphorus and organic matter in the tailings were very low. High concentrations
      of Pb, Zn, As and Cd as well as Cu were observed on some sites. The dominant
      plants growing on mine tailings belonged to the families Gramineae and
      Compositae, and the most widely distributed plant species were Imperata
      cylindrica, Cynodon dactylon and Paspalum distichum. Coreopsis drummondii also
      grew well on the arid sites but not on wet sites. Very low or zero arbuscular
      mycorrhizal (AM) fungal colonization was observed in most of the plants, but
      extensive mycorrhizal colonization was recorded in the roots of C. drummondii and
      C. dactylon. Metal concentrations in plant tissues indicated that I. cylindrica
      and P. distichum utilized avoidance mechanisms to survive at high metal
      concentrations. The investigation suggests that remediation and revegetation of
      heavy metal contaminated sites might be facilitated by selection of tolerant
      plant species. Isolation of tolerant AM fungi may also be warranted.

PMID- 16089343
TI  - Chromate and selenate hydrocalumite solid solutions and their applications in
      waste treatment.
AB  - Hydrocalumite, a calcium aluminate hydrate phase, consists of positively-charged
      structure units, and is therefore an ideal candidate for accommodating anionic
      contaminants. In this study, a series of batch experiments was carried out to
      examine the uptake of chromate and selenate by hydrocalumite. To determine the
      uptake capacity and long-term stability, hydrocalumite solid solutions between
      chromate/selenate and hydroxyl were synthesized over a reaction time of more than
      one year. At a ratio of water to initial solids added (CaAl2O4+CaO) of 75:1, the
      maximum uptake capacities were over 77 and 114 g/kg for Cr and Se, respectively.
      These values are very close to the theoretical uptake capacities of chromate and
      selenate hydrocalumite end-members (81 and 118 g/kg, respectively). The oxyanion
      removal efficiency from solution was above 95%. Due to the high uptake capacity
      and anion removal efficiency of hydrocalumites, their application in wastewater
      treatment is promising. Hydrocalumites are also important hydration products of
      cementitious materials and the long-term stability of these phases is of
      significance for application in solidification/stabilization technology.

PMID- 16089344
TI  - Lipid transport into bile and role in bile formation.
AB  - Biliary lipid secretion is driven by bile salts, the primary metabolites of
      cholesterol. Transport of bile salts as well as phospholipids and cholesterol is
      mediated by ATP Binding Cassette (ABC) transporters. Expression of these
      transporters is regulated in a coordinate fashion by a set of nuclear hormone
      receptors explaining the old observation of coupling between bile salt secretion
      and biliary lipid secretion. Although it is now clear which proteins are
      involved, the molecular mechanism of biliary lipid secretion is still unresolved.
      In addition, scarce information is available about the systems responsible for
      intracellular transport of cholesterol, phospholipid and bile salt. These issues
      form the subject of the review.

PMID- 16089345
TI  - Water transport into bile and role in bile formation.
AB  - Formation of bile and generation of bile flow are driven by the active secretion
      of bile salts (BS), lipids and electrolytes into the canalicular and bile duct
      lumens followed by the osmotic movement of water. Although the transporting
      proteins involved in solute secretion have been cloned and their coordinated
      interplay defined both in health and disease, boosted by the discovery of the
      aquaporin water channels, only recently has considerable attention been addressed
      to the mechanism by which water, the major component of bile (> 95%), moves
      across the hepatobiliary epithelia. This review summarizes the novel acquisitions
      in liver membrane water transport and functional participation of aquaporin water
      channels in multiple aspects of hepatobiliary fluid balance. Emerging evidences
      suggesting involvement of aquaporins in the metabolic homeostasis of the
      hepatobiliary tract are also discussed.

PMID- 16089346
TI  - Ion transport across the gallbladder epithelium.
AB  - The function of the gallbladder is not only to store bile, but also to
      concentrate it during the interdigestive phase by means of salt-dependent water
      reabsorption. On the contrary, secretions of water and salt take place during the
      digestive phase. Dysregulation of ion absorption or secretion are common in many
      gallbladder diseases, such as colelithiasis. Transepithelial absorptions are
      determined by the Na+/K+ pump on the basolateral membrane, and by several apical
      membrane Na(+)-coupled transporters. Among these, some isoforms of Na+/H+ and Cl
      /HCO3(-) exchangers have been studied. The presence of a Na(+)-Cl(-) simport has
      been molecularly and functionally characterized in some animal species. The ion
      transepithelial secretion is mainly dependent on an apical chloride transport
      attributable to a CFTR-like cAMP-activated channel with high permeability to
      HCO3(-). The apical membrane electrical potential is one of the factors
      influencing anion secretion and is maintained by the activity of cAMP-dependent
      K+ channels. The regulation of the activity of these channels is complex, because
      of their sensitivity to voltage, and to intracellular calcium and pH. The
      coordinated interplay underlying the regulation of transporters and channels
      needs to be clarified yet, as well as the interactions between transporters,
      channels and aquaporins.

PMID- 16089347
TI  - Contribution of canalicular glutathione efflux to bile formation. From
      cholestasis associated alterations to pharmacological intervention to modify bile
      flow.
AB  - At least one third of the bile flow is driven osmotically by the amount of
      hepatic glutathione excreted into canalicular spaces. Beyond the importance of
      this secretory mechanism for bile formation, the excretion of glutathione is an
      important way to discharge toxic anionic compounds deriving from liver metabolism
      of exogenous and endogenous substances. Thus, biliary secretion of glutathione
      and its conjugates really works as a major detoxification system for the
      hepatocytes. Derangement of hepatic and/or biliary glutathione status can occur
      in several experimental animal models of liver injury and in human diseases. In
      the present review, we will focus on mechanisms of bile glutathione efflux and
      changes associated with cholestatic conditions. Novel findings on the role of
      water channels and of the multidrug resistant proteins in bile salt-independent
      bile formation, will also be discussed. New routes of intervention to modify bile
      flow for therapeutic purposes are considered.

PMID- 16089348
TI  - The genetic background of cholesterol gallstone formation: an inventory of human
      lithogenic genes.
AB  - Family and twin studies as well as animal studies indicate that gallstone disease
      is, in part, genetically determined. Recently new single gene defects have been
      identified in specific patients with cholesterol and pigment gallstones. Examples
      include low phospholipid-associated cholelithiasis due to mutations of the gene
      encoding the hepatocanalicular phosphatidylcholine transporter, and pigment
      stones in association with mutations of the ileal bile salt transporter gene.
      Here we summarize the evidence for common genetic determinants of human gallstone
      disease in general and provide an inventory of human lithogenic genes. The
      precise understanding of such genes and their molecular mechanisms will establish
      new targets for rational drugdesign for this exceptionally prevalent and
      economically significant digestive disease.

PMID- 16089349
TI  - Effects of fatty acid bile acid conjugates (FABACs) on biliary lithogenesis:
      potential consequences for non-surgical treatment of gallstones.
AB  - Fatty acid bile acid conjugates (FABACs) are novel synthetic lipid molecules,
      which were designed for the treatment of cholesterol gallstones. The rationale
      was to combine a cholesterol solubilizing moiety (a saturated fatty acid) with a
      bile acid (cholic acid) as a vehicle to enable secretion into bile and entry into
      the enterohepatic circulation. An amide bond was used to provide stability
      against intestinal degradation. Initial in vitro studies showed that FABACs are
      indeed cholesterol solubilizers, able to prevent biliary cholesterol
      crystallization. Arachidyl-amido-cholanoic acid (Aramchol) was found to be the
      most potent FABAC in these studies. Animal studies revealed that Aramchol was
      absorbed after oral administration and could prevent cholesterol crystallization
      as well as dissolve preformed crystals in rodents fed a lithogenic diet. In
      gallstone susceptible mice, Aramchol prevented gallstone formation and dissolved
      gallstones. FABACs were found to be metabolically active substances, also able to
      decrease blood cholesterol, atherosclerotic plaques and fat accumulation in the
      liver in several animal species. The underlying mechanisms of action are under
      active investigation, and several effects, e.g. on cholesterol and bile salt
      metabolizing enzymes as well as cholesterol efflux from cells have been
      discovered. These findings are, however, only the beginning of our understanding
      of the metabolic actions as well as the potential of use of FABACs as therapeutic
      agents.

PMID- 16089350
TI  - Modulation of cholesterol crystallization in bile. Implications for non-surgical
      treatment of cholesterol gallstone disease.
AB  - The first step in cholesterol gallstone disease is precipitation of cholesterol
      crystals in bile. In gallbladder bile. cholesterol is normally solubilized
      together with bile salts and phospholipids to form mixed micellar structures.
      When cholesterol in bile is in excess, vesicles (i.e. phospholipid-cholesterol
      globular structures: liquid crystals) form which become supersaturated in
      cholesterol. Early aggregation and precipitation of cholesterol molecules into
      submicroscopic nuclei occurs from these supersaturated vesicles. This crucial
      step is followed by precipitation and agglomeration of cholesterol crystals which
      then become visible at light microscopy. Here we describe the mechanism of
      cholesterol crystallization and its modulation in vivo and in vitro. Recent
      advances on the role of ursodeoxycholate as an agent preventing the precipitation
      of cholesterol crystals in bile will be highligthed.

PMID- 16089351
TI  - Drugs affecting biliary lipid secretion and gallbladder motility: their potential
      role in gallstone treatment and prevention.
AB  - Gallstone disease in the Western world has an estimated prevalence of 10-15% and
      more than 75% are cholesterol-enriched gallstones. Defective gallbladder motility
      has been identified as an important pathogenic factor for cholesterol gallstone
      disease. Various agents may enhance or impair postprandial gallbladder motility,
      and their effects on interdigestive gallbladder and intestinal motility should
      also be taken into account. Patients in high-risk situations for gallstone
      disease, and those chronically treated with drugs inhibiting gallbladder motility
      (e.g. somatostatin analogues) may benefit from improving gallbladder motility
      with prokinetic agents. Whether such a strategy can really prevent gallstone
      formation is still unknown, long-term studies are lacking so far. The efficacy of
      bile acid therapy with UDCA for gallstone dissolution or for prevention in high
      risk patients is limited and hampered by high recurrence rates. The efficacy of
      UDCA in prevention of colics or gallstone related complications in symptomatic
      patients with gallbladder stones with contraindications for operation or on the
      waiting list should be explored further, since several retrospective studies
      showed favourable outcomes with this strategy.

PMID- 16089352
TI  - Pharmacological manipulation of biliary water and lipids: potential consequences
      for prevention of acute biliary pancreatitis.
AB  - Acute biliary pancreatitis, caused by macroscopic cholesterol gallstones or
      microlithiasis, is often a severe disease with considerable morbidity and
      mortality. Formation of cholesterol gallstones and microlithiasis is caused by
      cholesterol crystallization from cholesterol supersaturated gallbladder bile.
      Particularly patients with fast and extensive crystallization, due to highly
      concentrated bile, low biliary phospholipid contents and gallbladder mucin
      hypersecretion seem at risk for pancreatitis. Patients who suffered from acute
      biliary pancreatitis should undergo cholecystectomy as secondary prevention
      strategy. For patients at high surgical risk, endoscopic sphincterotomy may be an
      appropriate alternative. Pharmacological manipulation of biliary lipids by the
      hydrophilic bile salt ursodeoxycholic acid is reserved for patients with
      recurrent pancreatitis despite previous cholecystectomy or sphincterotomy, or
      with contraindications to surgical and endoscopic treatment. Maintenance therapy
      with ursodeoxycholic acid is however a very effective secondary prevention
      strategy. Potentially, secondary prevention of acute biliary pancreatitis could
      also be achieved through decreasing biliary mucin contents by UDCA, NSAIDs or N
      acetylcystein, or through achieving bile dilution (currently not feasible).

PMID- 16089353
TI  - Manipulation of biliary lipids by gene therapy: potential consequences for
      patients with progressive familial intrahepatic cholestasis.
AB  - Gene therapy constitutes a great promise for the treatment of inherited diseases
      as well as cancer. Although the principle is extremely elegant, reality proves
      that several important problems remain to be solved before gene therapy becomes a
      standard application for these conditions. Meanwhile, and because of these
      problems alternatives are being considered as well. For the treatment of hepatic
      inherited disorders, hepatocyte transplantation has proven to be an attractive
      alternative, although this form of therapy also remains experimental at this
      moment. Problems and possibilities are discussed with the inherited disease,
      Progressive Familial Intrahepatic Cholestasis, as an example.

PMID- 16089354
TI  - Effects of leptin on biliary lipids: potential consequences for gallstone
      formation and therapy in obesity.
AB  - Gallstone disease is exceptionally common, occurring especially in Western
      populations, with cholesterol gallstones predominating. Currently, it is believed
      that obesity is the most consistent and important risk factor for the development
      of cholesterol gallstones. Obesity has been shown to be associated with the
      supersaturation of bile with cholesterol because of increased hepatic secretion
      of the sterol. In accord with current information from experimental studies,
      leptin appears to be involved in biliary cholesterol secretion and cholesterol
      gallstone formation in humans. This review summarizes the current information on
      the role of obesity in biliary lipid secretion as well as the effect of leptin
      and its potential consequences for gallstone formation and therapy in the obese.

PMID- 16089355
TI  - Assessment of modes of action and efficacy of plasma cholesterol-lowering drugs:
      measurement of cholesterol absorption, cholesterol synthesis and bile acid
      synthesis and turnover using novel stable isotope techniques.
AB  - Several processes are involved in control of plasma cholesterol levels, e.g.,
      intestinal cholesterol absorption, endogenous cholesterol synthesis and transport
      and bile acid synthesis. Adaptation of either of these processes allows the body
      to adapt to changes in dietary cholesterol intake. Disturbances herein may lead
      to hypercholesterolemia and increase the risk for atherosclerosis. Several
      approaches are available for plasma-cholesterol lowering therapies, particularly
      aimed at reduction of low-density lipoprotein (LDL) cholesterol. Currently used
      therapies aim to decrease (hepatic) cholesterol synthesis, to inhibit cholesterol
      absorption or to stimulate bile acid synthesis. The latter can be achieved by
      reducing bile acid absorption to alleviate the negative feedback control exerted
      by bile acids circulating in the body. Approaches to directly stimulate bile acid
      synthesis may become available. Novel drugs should be tested on the efficiency to
      influence their actual targets. Several techniques are available to measure
      cholesterol absorption, cholesterol synthesis and bile acid synthesis and
      absorption in vivo in human subjects. The most reliable techniques are based on
      the use of stable isotopes and mass spectrometry. This paper provides a condensed
      background on physiological parameters that determine cholesterol homeostasis,
      and potential new mechanisms of drug action and focuses, especially, on new
      techniques to monitor the effects of drugs in humans.

PMID- 16089357
TI  - Therapeutic targets for the prevention of type 1 diabetes mellitus.
AB  - The pathogenesis of type 1 diabetes is multifactorial, involving genetic
      susceptibility, autoimmune mechanisms, and environmental factors. This article
      will focus on two main strategies for altering the underlying disease process in
      type 1 diabetes. The first strategy is to identify individuals at risk for the
      development of diabetes and to halt the immune process before it leads to overt
      clinical disease, Promising in vitro and animal studies with nicotinamide,
      parenteral insulin, and oral insulin led to large clinical prevention studies,
      such as the European Nicotinamide Diabetes Intervention Trial and the Diabetes
      Prevention Trial (DPT-1). These studies failed to show that nicotinamide and
      insulin prevented the disease in at risk relatives of patients with type 1
      diabetes and left many questions unanswered. The second strategy focuses on
      intervention shortly after diagnosis in order to arrest the destruction of beta
      cells and to preserve residual beta-cell function as long as possible.
      Cyclosporin was an effective immunosuppressive but was rejected as a potential
      treatment for type 1 diabetes because of its renal toxicity. Recently, more
      attention has been focused on an anti-CD3 antibody, on DiaPep277, and on glutamic
      acid decarboxylase (GAD). Animal studies and small short-term human trials with
      these compounds have suggested that they may be effective interventions in
      patients recently diagnosed with type 1 diabetes.

PMID- 16089356
TI  - Myocardial insulin resistance and cardiac complications of diabetes.
AB  - Cardiovascular disease is a major cause of mortality and morbidity in individuals
      with obesity, type 2 diabetes and the metabolic syndrome. The mechanisms for this
      are partially understood, but include increased atherosclerosis,
      hypercoagulability and increased hypertension. Epidemiological data suggests
      however, that a component of the excess cardiovascular mortality occurs
      independently of underlying coronary artery disease. Indeed, diabetes is an
      independent risk factor for the development of heart failure and the mechanisms
      responsible remain to be clarified. Insulin resistance in skeletal muscle,
      adipose tissue and the liver are widely recognized features of obesity and type 2
      diabetes, and contribute to the pathogenesis of impaired glucose homeostasis.
      Insulin resistance has also been described in the vasculature, and may contribute
      to endothelial dysfunction and atherosclerosis. The heart is an insulin
      responsive organ and less is known about whether or not the heart becomes insulin
      resistant in diabetes and what the pathogenic consequences of this might be. This
      review will discuss the currently available evidence from human and animal
      studies, that the heart may become insulin resistant in obesity and type 2
      diabetes. The potential consequences of this on cardiac structure, function and
      metabolism will be discussed as well as recent data from transgenic mice with
      perturbed cardiac insulin sensitivity that have shed interesting new insight into
      potential mechanisms linking cardiac insulin resistance with myocardial
      dysfunction in diabetes.

PMID- 16089358
TI  - The mammalian innate immune system: potential targets for drug development.
AB  - The innate immune system is the oldest mammalian defence against invading micro
      organisms and provides the first line of defence against them, however until
      recently a detailed understanding of its complexity has been lacking. This review
      describes recent advances that have been made in understanding the components of
      the innate immune system, including the pathogen sensing mechanisms, receptor and
      intracellular signalling pathways, linkage to the acquired immune system, and
      effectors of the innate immune response. These discoveries have created an
      opportunity for the development of novel drugs through the identification of
      targets for rational drug design. The opportunity for the development of novel
      anti-inflammatory and antimicrobial drugs through modulation of pro-inflammatory
      or antimicrobial signals within the innate immune system, are discussed. A more
      detailed understanding of the effectors of the innate immune system is providing
      an opportunity for the design of effector mimetics as novel antimicrobial drugs.
      The innate immune system is providing the basis for much-needed alternative
      approaches to controlling infection and inflammation in human medicine.

PMID- 16089359
TI  - Using the chorions of fertilized zebrafish eggs as a biomaterial for the
      attachment and differentiation of mouse stem cells.
AB  - The development of proper biomaterials is critical for the success of cell
      therapy and modern tissue engineering. Here, we extruded the yolk and remaining
      inner mass from fertilized zebrafish eggs and used the resulting chorions as a
      biomaterial for the differentiation and attachment of mouse P19 embryonic
      carcinoma (EC) cells. Cells inserted into the chorion showed the spontaneous
      formation of embryoid body due to the repulsive cell adhesion of the chorion and
      differentiated specifically into neural cells and cardiomyocytes. In contrast,
      dissolved chorion extracellular matrix (ECM) conferred enhanced cell attachment
      on it, suggesting that a unique property of the zebrafish chorion with nanoporous
      structure appears to be responsible for the simple and controllable embryoid
      formation for stem cell differentiation. These results indicate that chorions
      from fertilized zebrafish eggs may be used as an extracellular matrix alternative
      and applied for stem cell differentiation to specific cell lineages.

PMID- 16089360
TI  - Functional antibody immobilization on 3-dimensional polymeric surfaces generated
      by reactive ion etching.
AB  - Reactive ion etching (RIE) was used to pattern antibodies onto the surfaces of
      polymer substrates. A low pressure, inductively coupled oxygen plasma was used to
      anisotropically etch 25-30 mum deep features into poly(methyl methacrylate)
      (PMMA), Zeonex, and polycarbonate (PC). Scanning electron microscopy and contact
      angle measurements show that the resulting surfaces exhibit significant
      microroughness and enhanced hydrophilicity. Fourier transform infrared
      spectroscopy suggests that, in addition to enhanced surface area, chemical
      modifications may contribute to antibody immobilization. Polyclonal antibodies
      preferentially bind to the etched areas in RIE-patterned PMMA and Zeonex
      substrates but localize in unetched regions of RIE-patterned PC surfaces. Simple
      immunoassays were performed to demonstrate a potential application for RIE
      modified polymer surfaces. Antibodies specific for the capture of fluorescently
      labeled cholera toxin, S. aureus enterotoxin B, and B. anthracis protective
      antigen were immobilized onto etched PMMA surfaces and shown to specifically
      capture their labeled antigen from solution. This work demonstrates a potentially
      useful fabrication methodology for constructing antibody microarrays on plastic
      substrates.

PMID- 16089361
TI  - Reversible photoswitching in a cell-sized vesicle.
AB  - A photosensitive amphiphilic molecule can switch the shape of an assembled
      vesicle as determined by microscopic observation. Photoisomerization induces a
      change in membrane fluctuation behavior or a morphological transition between
      ellipsoid and bud shapes, depending on the asymmetrical degree of the initial
      shape. The mechanism of this reversible photoswitching in the vesicle morphology
      is interpreted in terms of a change in the effective cross-sectional area of the
      photosensitive molecule.

PMID- 16089362
TI  - Novel asymmetric through-hole array microfabricated on a silicon plate for
      formulating monodisperse emulsions.
AB  - We have proposed a novel microchannel (MC) structure for formulating monodisperse
      emulsions. The emulsification device is a silicon array of microfabricated,
      asymmetric through-holes with a slit and a circular channel (an asymmetric
      straight-through MC). The asymmetric through-holes of a uniform size stably
      yielded monodisperse emulsions with average droplet diameters of 35-41 mum and
      coefficients of variation of less than 2% by forcing the to-be-dispersed phase
      into the continuous phase via the through-holes. Their asymmetry enabled the
      stable formation of monodisperse emulsion droplets by spontaneous transformation,
      even using a to-be-dispersed phase with a very low viscosity below 1 mPa s.
      Additionally, the asymmetric straight-through MC with a high-density through-hole
      layout has the potential for high-throughput formulation of monodisperse
      emulsions.

PMID- 16089363
TI  - Critical concentration for colloidal crystallization determined with microliter
      centrifuged suspensions.
AB  - We report an elegant method using centrifugal sedimentation for determining the
      critical particle concentration for colloidal crystallization. A small amount of
      a dilute suspension of monodispersed particles stored in a flat capillary cell
      was centrifuged to temporarily generate a nonequilibrium gradient of the particle
      concentration including a crystalline-noncrystalline phase boundary in the cell.
      In the recovering process after the centrifugation, the particle concentration of
      the crystalline phase at the boundary was found to always have the equilibrium
      value, although the global concentration distribution evolved with time. The
      critical concentration was determined based on spatially resolved spectrometry.
      The present method requires only one batch of a suspension of the order of
      microliters and is applicable up to high concentration regions near the closest
      packing without the effect of the particle aggregation.

PMID- 16089364
TI  - Novel cationic amphiphilic derivatives from vernonia oil: synthesis and self
      aggregation into bilayer vesicles, nanoparticles, and DNA complexants.
AB  - Self-assembling nanostructures were prepared from novel cationic amphiphilic
      compounds synthesized from vernonia oil, a natural epoxydized triglyceride. The
      presence of a 12,13-epoxy group on the C18 unsaturated fatty acid, vernolic acid,
      which is the main constituent of vernonia oil, permitted the synthesis of novel
      amphiphilic derivatives with a hydrogen-bonding hydroxyl and a cationic headgroup
      moiety on adjacent carbon atoms. The amphiphiles were prepared in a two-stage
      synthesis that comprised opening of the epoxy groups with a haloacetic acid,
      followed by quaternization of the halo group with a tertiary amine containing a
      C12 aliphatic chain. Intact vernonia oil as the starting material gave a triple
      headed cationic amphiphile, containing three vernolic acid derived moieties
      connected through a glycerol backbone. A single-headed amphiphile with two alkyl
      chains and a single quaternary ammonium headgroup was synthesized from the methyl
      ester of vernolic acid as the starting material. The triple-headed derivative
      could form nonencapsulating structures. Cholesterol was required in the
      formulation (1:1) to make spherical vesicles that could encapsulate a water
      soluble marker. The single-headed derivative, however, formed spherical
      encapsulating vesicles without cholesterol. TEM, NMR, and FT-IR were used to
      characterize the vesicles, and molecular structure vs morphology relationships
      were postulated on the basis of these data. The triple-headed amphiphile also
      formed a DNA complex that was highly resistant to hydrolysis by DNase. This
      amphiphile-DNA complex was used as vector for gene transfer in cell culture
      demonstrating efficient DNA transfection.

PMID- 16089365
TI  - Wormlike micelles mediated by polyelectrolyte.
AB  - Aqueous solutions of the anionic surfactant potassium oleate (K-oleate) were
      studied using small-angle neutron scattering (SANS), steady-state rheology, and
      cryogenic transmission electron microscopy (cryo-TEM). The micellar structural
      changes induced by the addition of potassium chloride (KCl) and sodium
      polystyrenesulfonate (PSS) of different molecular weights were investigated. Upon
      addition of KCl, a transition from spherical to wormlike micelles was detected
      from the SANS data and confirmed by the cryo-TEM pictures. The rheological
      measurements revealed a strong dependence of the low-shear viscosity on the
      concentration of salt: a broad maximum in the viscosity curve was observed upon
      addition of KCl, characteristic of the growth of micelles into long worms,
      followed by branching. The addition of PSS to salt-free solutions of K-oleate had
      a significant effect on the scattering patterns, revealing partial growth of the
      spherical micelles into rodlike micelles. In contrast, in the presence of high
      salt concentrations, addition of PSS to solutions of wormlike micelles did not
      bring any noticeable modifications in the scattering. However, in the same salt
      conditions, a clear effect was observed on the low shear viscosity upon addition
      of PSS, which was found to depend significantly on molecular weight. This
      suggests a novel way of impacting the viscosity of solutions of wormlike
      micelles.

PMID- 16089366
TI  - Interaction of cetylpyridinium chloride with giant lipid vesicles.
AB  - The interaction of cationic surfactant cetylpyridinium chloride, CPC, with giant
      lipid vesicles prepared from 1-palmitoyl-2-oleoylphosphatidylcholine, POPC, was
      examined at various concentrations of the lipid component. The lipid
      concentration was determined by a spectrophotometric method. The potentiometric
      method based on surfactant-selective electrode was used for the determination of
      surfactant concentration in the external water solution. From these results,
      moles of surfactant incorporated in the membrane per mole of lipid (parameter
      beta) and two kinds of partition coefficients were calculated. Their values were
      found to be considerably larger than the available literature data. A three stage
      process of surfactant-induced solubilization of lipid vesicles was observed.
      First, stable mixed bilayers form, which become saturated with CPC at a value
      beta(sat) larger than 0.8, which then gradually disintegrate. Just prior to the
      breakdown of the vesicular structure, formation of ellipsoidal vesicles was
      observed by optical microscopy. This phenomenon was attributed to the cooperative
      incorporation of surfactant into the bilayer. Fluorescence measurements have
      shown that the second stage in the solubilization process of POPC by the C16
      chain-length surfactant does not involve mixed micelles. These are formed only in
      the third stage, which is the complete solubilization of POPC bilayers. The
      corresponding critical micellization concentration decreases with increasing
      concentration of the lipid component.

PMID- 16089367
TI  - Investigation of the electrokinetic properties of paraffin suspension. 2. In
      cationic and anionic surfactant solutions.
AB  - Electrical phenomena at nonionogenic hydrophobic surfaces (solid or liquid) in
      water, electrolyte, and/or surfactant solutions still attract research. In part 1
      of this paper we described the electrokinetic behavior of paraffin wax suspension
      in water and electrolyte solutions (NaCl or LaCl3). On the basis of the latest
      data of water structure near hydrophobic surfaces it was concluded that
      immobilized water dipoles at the interface can play an essential role in the zeta
      potential formation. In this paper were investigated the zeta potentials of
      paraffin wax in cationic surfactants cetyltrimethylammonium bromide,
      C16H33(CH3)3NBr, and octadecyltrimethylammonium chloride, C18H37(CH3)3NCl, and
      anionic surfactant sodium dodecyl sulfate, C12H25SO4Na. Also changes in
      wettability of the paraffin surface due to the surfactant's adsorption were
      studied via wetting contact angle measurements and calculation of the surface
      free energy. It was concluded that at a low surfactant concentration (10(-6) M)
      the water dipole structure still contributes to the zeta potential, but at a
      higher one the zeta potential is determined by the surfactant molecules'
      adsorption. A special role of OH- ions is also clearly seen. Moreover, a
      functional relationship was found between the surface free energy of the
      surfactant-covered paraffin surface and the zeta potential.

PMID- 16089368
TI  - Ionizing power and nucleophilicity in water in oil AOT-based microemulsions.
AB  - A study was carried out on the solvolysis of substituted phenyl chloroformates in
      AOT/isooctane/water microemulsions. (AOT is the sodium salt of bis(2
      ethyhexyl)sulfosuccinate.) The results obtained have been interpreted by taking
      into account the distribution of the chloroformates between the continuous medium
      and the interface of the microemulsions, where the reactions take place. The
      values obtained for the rate constant in the interface, k(i), decreases as the
      water content of the microemulsions increases, as a consequence of the decrease
      in its nucleophilic capacity. This behavior is consistent with a rate-determining
      step of water addition to the carbonyl group. The values of k(i) allow us to
      obtain the slopes of the Hammett correlations at the interface of the
      microemulsions, rho = 2.25, whose values are greater than those obtained in an
      aqueous medium, rho = 0.82. This increase in the Hammett slope is similar to that
      observed in ethanol/water mixtures and is a consequence of a variation in the
      structure of the transition state of the reaction where there is a smaller
      extension of the expulsion of the leaving group. The values of the rate constants
      at the interface of the microemulsions have allowed us, by means of the Grunwald
      Winstein equation, to obtain the solvent ionizing power and the nucleophilicity
      of the solvent. The values obtained for Y(Cl) increase together with the water
      content of the microemulsion, whereas the values of N(T) decrease. These
      variations are a consequence of the interaction between the AOT headgroups and
      the interfacial water, where the water molecules act like electronic acceptors.
      The intensity of this interaction is greater if the system has a small water
      content, which explains the variation of Y(Cl) and N(T).

PMID- 16089369
TI  - Some properties of electrolyte solutions in nanoconfinement revealed by the
      measurement of transient filtration potential after pressure switch off.
AB  - We have demonstrated that with a composite nanoporous ceramic membrane in a batch
      membrane cell it is technically feasible to switch off the trans-membrane
      hydrostatic pressure difference within tens of milliseconds. That enabled us to
      resolve practically the whole time evolution of transient filtration potential.
      Measurements of the latter have been complemented by measurements of steady-state
      salt rejection by the composite membrane and by measurements of the streaming
      potential and hydraulic permeability of membrane supports available separately. A
      theory has been developed in terms of network thermodynamics for the electrical
      response of a bilayer membrane to a pressure perturbation. In combination with
      the results of salt rejection measurements, from the time transients of
      filtration potential we could determine the ion transport numbers within the
      nanoporous layer. Besides that, from the dependence of steady-state salt
      rejection on the trans-membrane volume flow, we have determined the diffusion
      permeability of and the salt reflection coefficient in the nanoporous layer. This
      has enabled us to estimate the contributions of Donnan and non-Donnan mechanisms
      to the rejection of ions by the nanoporous membrane used in this study. It has
      been unexpectedly found that the Donnan exclusion played only a secondary role.
      Our hypothesis is that the non-Donnan exclusion of ions from the nanopores might
      be caused by changes in water properties in nanoconfinement. Proceeding from the
      results of steady-state filtration experiments with the membrane and the support,
      we also concluded that the nanoporous layer was imperfection-free and had a quite
      narrow pore size distribution, which made it a suitable object for fundamental
      studies of ion transfer mechanisms in nanopores.

PMID- 16089370
TI  - Degree of micelle ionization and micellar growth for gemini surfactants detected
      by 6-methoxy-N-(3-sulfopropyl)quinolinium fluorescence quenching.
AB  - The degree of micelle ionization of gemini surfactants has been investigated by
      using halide-sensitive fluorescence probes (e.g., 6-methoxy-N-(3
      sulfopropyl)quinolinium (SPQ)). The fluorescence is quenched by the free bromide
      ions dissociated from surfactants. The degree of micelle ionization increased
      with increasing spacer chain length, but it decreased with increasing surfactant
      concentration. The Stern-Volmer plot gave two inflection points (i.e., not only
      at the cmc but also far above the cmc). The second inflection point suggested
      spherocylindrical micellar growth with decreases in the degree of micelle
      ionization. The spherocylindrical micellar growth was depressed with increasing
      spacer chain length, whereas it was enhanced with increasing tail chain length.
      The degree of micelle ionization of spherocylindrical micelles depended on the
      concentration and chain length of gemini surfactants. The change in SPQ
      fluorescence spectra upon hydrogenation was utilized to evaluate the
      solubilization site in micelle solutions. The dissolved SPQ in water was
      instantly reduced by the addition of NaBH4, resulting in abrupt changes in
      fluorescence intensity and spectral shift. All of the SPQ in micelle solution was
      also instantly reduced by NaBH4, indicating the existence of SPQ in the water
      bulk phase, but its fluorescence intensity increased upon the solubilization of
      hydrogenated SPQ into micelles.

PMID- 16089371
TI  - Conformational transition of the core chain in radiation-modified polysilane
      micelles formed in selective solvents.
AB  - Poly(methyl acrylate)-grafted poly(methyl-n-propylsilane) (PMPrS-g-PMA) and
      poly(acrylic acid)-grafted PMPrS (PMPrS-g-PAA) were synthesized by gamma-ray
      induced graft polymerization, and the association behavior of these graft
      copolymers was investigated in selective solvents composed of good and poor
      solvents for the PMPrS main chain. Fluorescence spectroscopy with perylene as a
      fluorescent probe revealed that PMPrS-g-PAA in a water/THF mixed solvent self
      assembles into micelles with a swollen core of PMPrS chains in the water content
      range of 50-95%. UV spectroscopy demonstrated that a further increase of the
      water content gives rise to the conformational transition of the PMPrS chains in
      the micelle core from the random conformation to the conformation that
      corresponds to that in the solid state at a water content of ca. 95%, independent
      of the grafting yield. Similar behavior was also observed in DMSO/THF solutions
      of PMPrS-g-PMA, for which the conformational transition occurred at the constant
      DMSO content of ca. 95%. These results indicate that solvatochromic behavior of
      polysilane, which is a characteristic feature of polysilane, proved to provide
      information on the inner structure of those micelles: PMPrS chains in the core
      undergo conformational transition as the content of the poor solvents for PMPrS
      increases, while maintaining the micelle structure.

PMID- 16089372
TI  - Magnetic resonance investigations of lipid motion in isotropic bicelles.
AB  - The dynamics of DMPC in different isotropic bicelles have been investigated by
      NMR and EPR methods. The local dynamics were obtained by interpretation of 13C
      NMR relaxation measurements of DMPC in the bicelles, and these results were
      compared to EPR spectra of spin-labeled lipids. The overall size of the bicelles
      was investigated by PFG NMR translational diffusion measurements. The dynamics
      and relative sizes were compared among three different bicelles: [DMPC]/[DHPC] =
      0.25, [DMPC]/[DHPC] = 0.5, and [DMPC]/[CHAPS] = 0.5. The local motion is found to
      depend much more strongly on the choice of the detergent, rather than the overall
      size of the bicelle. The results provide an explanation for differences in
      apparent dynamics for different peptides, which are bound to bicelles. This in
      turn determines under what conditions reasonable NMR spectra can be observed. A
      model is presented in which extensive local motion, in conjunction with the
      overall size, affects the spectral properties. An analytical expression for the
      size dependence of the bicelles, relating the radius of the bilayer region with
      physical properties of the detergent and the lipid, is also presented.

PMID- 16089373
TI  - Concomitant adsorption of poly(ethylene oxide)-b-poly(epsilon-caprolactone)
      copolymers and sodium dodecyl sulfate at the silica-water interface.
AB  - Upon addition of silica to aqueous solutions of poly(ethylene oxide)-b
      poly(epsilon-caprolactone) copolymers (PEO-b-PCL) and sodium dodecyl sulfate
      (SDS), adsorption of the solutes occurs at the silica-water interface. The amount
      of the adsorbed constituents has been measured by the total concentration
      depletion method. Small-angle neutron scattering experiments (SANS) have been
      carried out to investigate the structure of the adsorbed layer. Although SDS is
      not spontaneously adsorbed onto hydrophilic silica, adsorption is observed in the
      presence of PEO-b-PCL diblocks, in relation to the relative concentration of the
      two compounds. Conversely, SDS has a depressive effect on the adsorption of the
      copolymer, whose structure at the interface is modified. Copolymer desorption is
      however never complete at high SDS content. These observations have been
      rationalized by the associative behavior of PEO-b-PCL and SDS in water.

PMID- 16089374
TI  - Protolytic surface reactions of a fluorapatite-maghemite mixture in aqueous
      suspension.
AB  - Synthetically prepared maghemite and fluorapatite, characterized with BET, SEM,
      XRD, FT-IR, and FT-Raman, are used to investigate the protolytic properties and
      surface characteristics in a mixed system of maghemite and fluorapatite by means
      of potentiometric titrations and surface complex modeling. Titrations were
      performed in the pH range of 7.3-10.5 at 25 +/- 0.2 degrees C in ionic media of
      0.10 mol dm(-3) NaNO3 with 0.0100 mol dm(-3) HNO3 and 0.0100 mol dm(-3) NaOH used
      as titrants. The constant capacitance model (CCM) was applied to interpret the
      titration data. Two models with different surface equilibria were tested. In the
      first model, the mixed system was treated as a one-component system with a total
      surface area of 40.04 +/- 5.2 m2 g(-1) without any consideration to the
      subsystems. The surface equilibria, triple bond XOH + H+ <==> triple bond XOH2+,
      beta(s)(-11)(int) = 6.74 +/- 0.07; XOH <==> triple bond XO- + H+, beta(s)(
      11)(int) = -7.75 +/- 0.07, were found to represent an accurate model for the
      system, and the specific capacitance was optimized to 2.0 F m(-2). The number of
      active surface sites N(s) was found to be 1.2 sites nm(-2). This model has,
      however, no relation to the subsystems of maghemite and fluorapatite. The second
      model is related to the subsystems and displays the surface equilibria, triple
      bond S2OH<==> triple bond S2O- + H+, beta(s)(-101)(int) = -9.12 +/- 0.01; triple
      bond FeOH + H+<==> triple bond FeOH2+, lg beta(s)(-11)(int) = 6.80 +/- 0.01;
      triple bond FeOH<==>FeO- + H+, beta(s)(-11)(int) = -7.77 +/- 0.01, where S2OH is
      related to fluorapatite and FeOH is representing maghemite. Fluorapatite
      corresponds to the dominating active surface in the system. The specific
      capacitance was optimized to 18 F m(-2). The N(s) values were found to be 2.27
      sites nm(-2) for fluorapatite and 0.80 sites nm(-2) for maghemite. The N(s)
      values together with evidence from the FT-Raman and SEM investigations reveal
      that interactions between maghemite and fluorapatite surfaces occur during the
      titration. The acid-base properties and surface characteristics of the subsystems
      maghemite-H+ and fluorapatite-OH- using the CCM have been published earlier.

PMID- 16089375
TI  - Adhesion between chemically heterogeneous switchable polymeric brushes and an
      elastomeric adhesive.
AB  - We investigated the adhesive properties of binary heterogeneous polymer brushes
      made from end-functionalized polystyrene (PS) and poly(2-vinylpyridine) (P2VP)
      chains. The molecular organization of the mixed brush could be varied reversibly
      by exposure to selective solvents for PS (toluene) and for P2VP (acidic water).
      This exposure results in reversible switching of adhesive and wetting properties.
      The manner in which the adhesion switching occurs can be tuned by the composition
      of mixed brushes. However, the outer surface composition could be enriched more
      effectively in PS after the toluene treatment than in P2VP after the acidic water
      treatment. As a result, the mixed brush compositions that showed the largest
      difference in properties between an exposure to toluene and an exposure to water
      were the P2VP-rich compositions. Adhesive properties, tested against a soft
      hydrophobic pressure-sensitive adhesive (PSA) using a probe test, always showed
      smaller differences between solvent treatments than wetting properties with
      water, suggesting a much higher sensitivity of the hydrophobic/hydrophilic
      brushes to polar molecules than to nonpolar molecules.

PMID- 16089376
TI  - Improved methodology to measure surface tension and its application to
      polystyrene or poly(methyl methacrylate) in styrene solutions.
AB  - Several methods to measure surface tension involve some inconveniences when
      applied to moderate or highly viscous polymer solutions. Therefore, an improved
      version of the weight drop method (WDM) is proposed here. In addition, a
      comparative analysis of methods is carried out, including the drop profile (DPM),
      the selected planes (SPM), the WDM and the one proposed here (WDSM), finding that
      the WDSM is as easy to apply as the SPM and the WDM, although in practical
      conditions it is much more accurate than either of them. Moreover, the WDSM
      allows to reproduce the results that can be obtained using DPM, but, in general,
      it is much easier to implement and apply than such method. The WDSM was used to
      determine surface tension in polystyrene or poly(methyl methacrylate) in styrene
      solutions, where the dependence of such property with polymer average molecular
      weight and polymer concentration was experimentally evaluated.

PMID- 16089377
TI  - Spreading kinetics of water drops on self-assembled monolayers of thiols:
      significance of inertial effects.
AB  - Spreading of 5-15 microL water drops on self-assembled monolayers of 1
      hexadecanethiol and 11-mercapto-1-undecanol, both homogeneous and mixed
      compositions, formed on gold-coated silicon wafers or glass slides was recorded
      with a high-speed video camera. The time (t) evolution of the drop base diameter
      (D) during spreading was analyzed by a power law-correlation: D approximately
      t(n). The n value was found to increase from n = 0.3-0.5 for water drops on
      hydrophobic surfaces characterized by the advancing water contact angle of thetaA
      = 94-104 degrees to n = 0.5-0.8 on less hydrophobic surfaces (thetaA = 45-66
      degrees ). These experimental values were found to be of similar magnitude as the
      literature values reported for small drops and bubbles, which spread over a
      variety of different substrates including water and water-ethanol drops on self
      assembled monolayers of alkylsilanes, air bubbles in water on glass, molten
      metals on solid metals and ceramics, hydrocarbon drops on water, and others.
      Inertial effects, which are often not accounted for in the analysis of spreading
      results, appear to have an impact on the spreading kinetics of small drops in at
      least the first few milliseconds of the spreading phenomenon.

PMID- 16089378
TI  - Loading and release of charged dyes using ultrathin hydrogels.
AB  - The anionic dyes methyl orange (MO) and allura red (AR) were used as model drugs
      to assess the loading and release by layer-by-layer assembled ultrathin hydrogels
      prepared via the amide formation of poly(acrylic acid-co-N-isopropylacrylamide)
      with AAc contents of 5, 10, and 15 mol % plus poly(vinylamine hydrochloride). The
      amount of MO loaded was potentially controlled by changing the dye
      concentrations, film thickness, and AAc content of the copolymers. The release of
      AR was controlled by the NaCl concentration and pH. We conclude that the
      polymeric matrices of ultrathin hydrogels have great potential for the loading
      and release of charged drugs.

PMID- 16089380
TI  - Importance of structural and chemical heterogeneity of activated carbon surfaces
      for adsorption of dibenzothiophene.
AB  - The performance of various activated carbons obtained from different carbon
      precursors (i.e., plastic waste, coal, and wood) as adsorbents for the
      desulfurization of liquid hydrocarbon fuels was evaluated. To increase surface
      heterogeneity, the carbon surface was modified by oxidation with ammonium
      persulfate. The results showed the importance of activated carbon pore sizes and
      surface chemistry for the adsorption of dibenzothiophene (DBT) from liquid phase.
      Adsorption of DBT on activated carbons is governed by two types of contributions:
      physical and chemical interactions. The former include dispersive interactions in
      the microporous network of the carbons. While the volume of micropores governs
      the amount physisorbed, mesopores control the kinetics of the process. On the
      other hand, introduction of surface functional groups enhances the performance of
      the activated carbons as a result of specific interactions between the acidic
      centers of the carbon and the basic structure of DBT molecule as well as sulfur
      sulfur interactions.

PMID- 16089379
TI  - Microscopic interpretation of the dependence of the contact angle on roughness.
AB  - The macroscopic contact angle theta(m) of a liquid drop on a rough solid surface
      in the presence of a gas is calculated microscopically on the basis of a
      variational minimization of the total potential energy of the drop. Two limiting
      cases are considered: the liquid penetrates into the space between asperities
      (Wenzel regime) and the liquid resides on the top of asperities (Cassie-Baxter
      regime). Long-range as well as short-range interactions between the molecules of
      liquid, solid, and gas are taken into account. It was also assumed that small
      portions of insoluble gas are accumulated near the edges of the asperities during
      the formation of the droplet. The contact angle depends on several parameters
      involved in the microscopic interactions as well as on the fractions of solid
      surface between asperities, and of the surface of the asperities themselves, that
      are in contact with the liquid. It is shown that the theory can explain the
      nonlinear dependence of cos theta(m) on roughness observed by Krupenkin et al.
      [Krupenkin, T. N.; Taylor, J. A.; Schneider, T. M.; Yang, S. Langmuir 2004, 20,
      3824].(1).

PMID- 16089381
TI  - In situ determination of orientational distributions in Langmuir monolayers by
      total internal reflection fluorescence.
AB  - A new application of the polarized total internal reflection fluorescence (PTIRF)
      technique to study the orientation distribution of a fluorophore within a
      Langmuir monolayer in situ on an aqueous subphase is described. The technique
      utilizes the measurement of polarized fluorescence, excited by the evanescent
      field appearing upon total internal reflection. The excitation by the evanescent
      field is achieved by launching the beam into a prism that is brought into contact
      with the monolayer from above. We also show here that a combination of PTIRF of
      monolayers on water and those freshly deposited onto the prism by horizontal lift
      in the same experiment provide enough data to determine the dielectric constant
      of the actual local environment of the fluorophore in the monolayer to eliminate
      the ambiguity of the orientation determination, arising from uncertainty in the
      normal component of excitation field. The new technique was applied to several
      model systems: fatty acid monolayers containing amphiphilic dyes DiI or BODIPY
      and also a monolayer of a synthetic amphiphilic porphyrin-binding peptide AP0.
      This technique is more accurate than polarized epifluorescence (PEF) in
      determining the fluorophore orientation distribution due to the much higher
      normal component of the excitation, achievable in the evanescent field, and to
      the lack of surface vibrations caused by capillary waves. Comparison of the new
      PTIRF approach with PEF shows that the monolayer structure is not disturbed by
      weak van der Waals attachment to the hydrophobic substrate.

PMID- 16089382
TI  - Adsorption of nonionic surfactants on cellulose surfaces: adsorbed amounts and
      kinetics.
AB  - Kinetic and equilibrium aspects of three different poly(ethylene oxide)
      alkylethers (C12E5, C12E7, C14E7) near a flat cellulose surface are studied. The
      equilibrium adsorption isotherms look very similar for these surfactants, each
      showing three different regions with increasing surfactant concentration. At low
      surfactant content both the headgroup and the tail contribute to the adsorption.
      At higher surface concentrations, lateral attraction becomes prominent and leads
      to the formation of aggregates on the surface. The general shape of the isotherms
      and the magnitude of the adsorption resemble mostly those for hydrophilic
      surfaces, but both the ethylene oxide and the aliphatic segments determine
      affinity for the surface. The adsorption and desorption kinetics are strongly
      dependent on surfactant composition. At bulk concentrations below the CMC, the
      initial adsorption rate is attachment-controlled. Above the CMC, the micellar
      diffusion coefficient and the micellar dissociation rate play a crucial role. For
      the most hydrophilic surfactant, C12E7, both parameters are relatively large. In
      this case, the initial adsorption rate increases with increasing surfactant
      concentration, also above the CMC. For C12E5 and C14E7 there is no micellar
      contribution to the initial adsorption rate. The initial desorption kinetics are
      governed by monomer detachment from the surface aggregates. The desorption rate
      constants scale with the CMC, indicating an analogy between the surface
      aggregates and those formed in solution.

PMID- 16089383
TI  - Carboranethiol-modified gold surfaces. A study and comparison of modified cluster
      and flat surfaces.
AB  - Four different carboranethiol derivatives were used to modify the surfaces of
      gold nanoparticles and flat gold films. The novel materials engendered from these
      modifications are extraordinarily stable species with surfaces that support self
      assembled monolayers of 1-(HS)-1,2-C2B10H11, 1,2-(HS)2-1,2-C2B10H10, 1,12-(HS)2
      1,12-C2B10H10, and 9,12-(HS)2-1,2-C2B10H10, respectively. Surprisingly,
      characterization of these materials revealed that a number of molecules of the
      carboranethiol derivatives are incorporated inside the nanoparticles. This
      structural feature was studied using a number of techniques, including X-ray
      photoelectron spectroscopy (XPS), UV-vis, and IR spectroscopies. Thermal
      desorption experiments show that carborane molecules detach and leave the
      nanoparticle surface mostly as 1,2-C2B10H10 isotopic clusters, leaving sulfur
      atoms bound to the gold surface. The surfaces of both the gold nanoparticles and
      the flat gold films are densely packed with carboranethiolate units. One
      carborane cluster molecule occupies an area of six to seven surface gold atoms of
      the nanoparticle and eight surface gold atoms of the flat film. XPS data showed
      that molecules of 1,12-(HS)2-1,12-C2B10H10 bind to the flat gold surface with
      only half of the thiol groups due to the steric demands of the icosahedral
      carborane skeleton. Electrochemical measurements indicate complete coverage of
      the modified gold surfaces with the carboranethiol molecules.

PMID- 16089384
TI  - Effect of time on the interfacial and foaming properties of beta
      lactoglobulin/acacia gum electrostatic complexes and coacervates at pH 4.2.
AB  - The electrostatic complexation between beta-lactoglobulin and acacia gum was
      investigated at pH 4.2 and 25 degrees C. The binding isotherm revealed a
      spontaneous exothermic reaction, leading to a DeltaHobs = -2108 kJ mol(-1) and a
      saturation protein to polysaccharide weight mixing ratio of 2:1. Soluble
      electrostatic complexes formed in these conditions were characterized by a
      hydrodynamic diameter of 119 +/- 0.6 nm and a polydispersity index of 0.097. The
      effect of time on the interfacial and foaming properties of these soluble
      complexes was investigated at a concentration of 0.1 wt % at two different times
      after mixing (4 min, referred as t approximately 0 h and t = 24 h). At t
      approximately 0 h, the mixture is mainly made of aggregating soluble
      electrostatic complexes, whereas after 24 h these complexes have already
      insolubilize to form liquid coacervates. The surface elasticity, viscosity and
      phase angle obtained at low frequency (0.01 Hz) using oscillating bubble
      tensiometry revealed higher fluidity and less rigidity in the film formed at t
      approximately 0 h. This observation was confirmed by diminishing bubble
      experiments coupled with microscopy of the thin film. It was thicker, more
      homogeneous and contained more water at t approximately 0 h as compared to t = 24
      h (thinner film, less water). This led to very different gas permeability's of Kt
      approximately 0 h = 0.021 cm s(-1) and Kt=24 h) = 0.449 cm s(-1), respectively.
      Aqueous foams produced with the beta-lactoglobulin/acacia gum electrostatic
      complexes or coacervates exhibited very different stability. The former (t
      approximately 0 h) had a stable volume, combining low drainage rate and mainly
      air bubble disproportionation as the destabilization mechanism. By contrast,
      using coacervates aged for 24 h, the foam was significantly less stable,
      combining fast liquid drainage and air bubble destabilization though fast gas
      diffusion followed by film rupture and bubble coalescence. The strong effect of
      time on the air/water interfacial properties of the beta-lactoglobulin/acacia gum
      electrostatic complexes can be understood by their reorganization at the
      interface to form a coacervate phase that is more fluid/viscous at t
      approximately 0 h vs rigid/elastic at t = 24 h.

PMID- 16089385
TI  - Printing chemical gradients.
AB  - We describe a method to exploit the mass-transfer limitations of microcontact
      printing for the fabrication of surfaces with well-defined, arbitrarily shaped
      composition variations. An analysis of the transport processes reveals that the
      printing of hexadecanethiol (HDT) from poly(dimethylsiloxane) is purely diffusion
      controlled. Stamps with geometries that enhance surface-normal diffusion paths
      therefore allow not only the contours, but also the local density of self
      assembled monolayers to be controlled. We use stamps with variable thickness and
      uniform ink concentration to print HDT density gradients on gold, depleting the
      stamps during the process. In the second step, a perfluorinated thiol fills the
      vacancies in the partial monolayer to form a two-component gradient that we
      analyze by means of X-ray photoelectron spectroscopy and spectroscopic
      ellipsometry. Linear and radial gradients are shown here as examples for a wide
      range of geometries that can be fabricated with high precision using the method.

PMID- 16089386
TI  - Investigating the interface of superhydrophobic surfaces in contact with water.
AB  - Neutron reflectivity (NR) is used to probe the solid, liquid, vapor interface of
      a porous superhydrophobic (SH) surface submerged in water. A low-temperature, low
      pressure technique was used to prepare a rough, highly porous organosilica
      aerogel-like film. UV/ozone treatments were used to control the surface coverage
      of hydrophobic organic ligands on the silica framework, allowing the contact
      angle with water to be continuously varied over the range of 160 degrees
      (superhydrophobic) to <10 degrees (hydrophilic). NR shows that the
      superhydrophobic nature of the surface prevents infiltration of water into the
      porous film. Atomic force microscopy and density functional theory simulations
      are used in combination to interpret the NR results and help establish the
      location, width, and nature of the SH film-water interface.

PMID- 16089387
TI  - Covalent molecular assembly of oligoimide ultrathin films in supercritical and
      liquid solvent media.
AB  - An ultrathin film of oligoimide has been fabricated on amine-modified substrates
      of silicon and quartz through alternate layer-by-layer (LBL) assembly of
      pyromellitic dianhydride (PMDA) and diaminodiphenyl ether (DDE), with interlayer
      links established by covalent bonds. The assembly was formed in supercritical
      carbon dioxide (SCCO2) and in solution (dimethyl acetamide, DMAc), and the
      imidization reaction was performed by thermal and chemical methods, in benzene
      and in the supercritical medium. X-ray photoelectron and UV-visible absorption
      spectroscopies, atomic force microscopy (AFM), and ellipsometry were employed to
      study the interfacial chemistry, growth, morphology, and thickness of the
      assembled film. XPS analysis confirmed the sequential deposition of PMDA and DDE
      through formation of amic acids. At each deposition step, surface functionalities
      for the assembly of the next layer were generated. The interfacial chemical
      reaction was almost complete in the SCF (supercritical fluid) medium, as compared
      to the conversions observed in conventional assembly. Both the PMDA and DDE
      molecules were assembled in an organized manner, resulting in uniform surface
      morphology. Uniform film growth was revealed from the increase of UV absorption
      intensity and film thickness. The overall growth and quality of the films in SCF
      medium were greater than that for films formed in DMAc. The results of this novel
      study show that an environmentally friendly solvent can be used to obtain
      mechanically robust and thermally stable ultrathin films with little loss of
      material during the imidization step. In contrast to conventional deposition of
      the molecular layers that utilizes liquid solvents, use of SCCO(2) avoids solvent
      effects and posttreatment for solvent removal, while ensuring facile transport
      during contact.

PMID- 16089388
TI  - Photoreductive self-assembly from [Mo7O24]6- to carboxylates-coordinated {Mo142}
      Mo-blue nanoring in the presence of carboxylic acids.
AB  - The primary steps of the photoredox reaction between [Mo7O24]6- and carboxylic
      acid electron (and proton) donors in aqueous solutions are investigated by the
      chemically induced dynamic electron spin polarization (CIDEP) spectroscopy. The
      excitation of the O-->Mo ligand-to-metal charge-transfer (LMCT) bands of
      [Mo7O24]6- in the presence of CH3CO2H induces the emissive electron spin
      polarization (ESP) of *CH2CO2 and *CH3 radicals with an accompanying formation of
      the one-electron reduced species [Mo7O23(OH)]6-, which is demonstrated by the
      triplet mechanism involving the O --> Mo LMCT triplet states. The prolonged
      photolysis of the solution containing [Mo7O24]6- and CH3CO2H at pH = 3.4 leads to
      the formation of the acetate/propionate-coordinated {Mo142} Mo-blue nanoring,
      [MoV28MoV(I)114O429H10(H2O)(49)(CH3)CO2 triple bond Ac5(C2H5CO2 triple bond
      Pr)]30- (1a) through the formation of the cis-configured dimeric dehydrative
      condensation to two-electron reduced Mo-blue [(Mo7O23)2]10- ({Mo14}). 1a is
      isolated as a [NH4]+/[Me3NH]+-mixed salt which is formulated as
      [NH4]27[Me3NH]3[Mo(V)28Mo(VI)114O429H10(H2O)49(CH3CO2)5(C2H5CO2)].150 +/- 10H2O
      (1) by results of elementary analysis, single-crystal X-ray analysis, 1H NMR, IR,
      and UV/Vis measurements, and manganometric redox titration. Based on the building
      block sequence of for 1a, the bottom-up processes from [Mo7O24]6- to the {Mo142}
      ring in the coexistence of beta-[Mo8O26]4- are discussed by (i) the stabilization
      of the molecular curvature of {Mo14} through both the intramolecular transfer of
      monomolybdates and the intermolecular transfer of monomolybdates as degradation
      fragments of beta-[Mo8O26]4-, to yield {Mo21} and {Mo20} building blocks, (ii)
      the outer-ring formation resulting from seven successive two-electron
      photoreductive condensations among {Mo21} and {Mo20}, and (iii) inner-ring
      formation resulting from eight successive dehydrative condensations between
      monomolybdate linkers attached to the neighboring head Mo sites.

PMID- 16089390
TI  - Chiral electrochemical recognition by very thin molecularly imprinted sol-gel
      films.
AB  - Thin films with enantioselective properties for electrochemically active chiral
      probes were developed. Enantioselectivity was accomplished via molecular
      imprinting. The films were fabricated through the sol-gel technique and were spin
      coated on ITO electrodes. The chiral selectivity recognition was detected using
      two enantiomer pairs: D- and L-3,4-dihydroxyphenylalanine (D- and L-dopa) and (R)
      and (S)-N,N'-dimethylferrocenylethylamine [(R)-Fc and (S)-Fc]. A defined chiral
      cavity was obtained by selection of functional monomers that interact with the
      template molecule, followed by its removal. Chiral selection properties were
      measured by cyclic voltammetry and square wave voltammetry. For both template
      molecules, very good chiral recognition was revealed by electrochemical
      measurement. The nonspecific adsorption measured for reference nonimprinted films
      was negligible (less than 5%). Dopa imprinted films revealed both high
      sensitivity, by the detection of 1 nM (0.2 ppb) concentration, and excellent
      selectivity, when challenged with a series of catechol derivatives. Fc-imprinted
      films were able to detect ca. 2 ppm of the target molecule, with very good
      enantioselectivity and low nonspecific adsorption. To our knowledge, this is the
      first report of successful molecular imprinting of a ferrocene derivative.

PMID- 16089389
TI  - Surface chemical and mechanical properties of plasma-polymerized N
      isopropylacrylamide.
AB  - Surface-immobilized poly(N-isopropyl acrylamide) (pNIPAM) is currently used for a
      wide variety of biosensor and biomaterial applications. A thorough
      characterization of the surface properties of pNIPAM thin films will benefit
      those applications. In this work, we present analysis of a plasma-polymerized
      NIPAM (ppNIPAM) coating by multiple surface analytical techniques, including time
      of-flight secondary-ion mass spectrometry (ToF-SIMS), contact angle measurement,
      atomic force microscopy (AFM), and sum frequency generation (SFG) vibrational
      spectroscopy. ToF-SIMS data show that the plasma-deposited NIPAM polymer on the
      substrate is cross-linked with a good retention of the monomer integrity. Contact
      angle results confirm the thermoresponsive nature of the film as observed by a
      change of surface wettability as a function of temperature. Topographic and force
      distance curve measurements by AFM further demonstrate that the grafted film
      shrinks or swells depending on the temperature of the aqueous environment. A
      clear transition of the elastic modulus is observed at 31-32 degrees C. The
      change of the surface wettability and mechanical properties vs temperature are
      attributed to different conformations taken by the polymer, which is reflected on
      the outmost surface as distinct side chain groups orienting outward at different
      temperatures as measured by SFG. The results suggest that a ppNIPAM thin film on
      a substrate experiences similar mechanical and chemical changes to pNIPAM bulk
      polymers in solution. The SFG result provides evidence supporting the current
      theory of the lower critical solution temperature (LCST) behavior of pNIPAM.

PMID- 16089391
TI  - DNA hybridization detection at heated electrodes.
AB  - The detection of DNA hybridization is of central importance to the diagnosis and
      treatment of genetic diseases. Due to cost limitations, small and easy-to-handle
      testing devices are required. Electrochemical detection is a promising
      alternative to evaluation of chip data with optical readout. Independent of the
      actual readout principle, the hybridization process still takes a lot of time,
      hampering daily use of these techniques, especially in hospitals or doctor's
      surgery. Here we describe how direct local electrical heating of a DNA-probe
      modified gold electrode affects the surface hybridization process dramatically.
      We obtained a 140-fold increase of alternating current voltammetric signals for
      20-base ferrocene-labeled target strands when elevating the electrode temperature
      during hybridization from 3 to 48 degrees C while leaving the bulk electrolyte at
      3 degrees C. At optimum conditions, a target concentration of 500 pmol/L could be
      detected. Electrothermal regeneration of the immobilized DNA-probe strands
      allowed repetitive use of the same probe-modified electrode. The surface coverage
      of DNA probes, monitored by chronocoulometry of hexaammineruthenium(III), was
      almost constant upon heating to 70 degrees C. However, the hybridization ability
      of the probe self-assembled monolayer declined irreversibly when using a 70
      degrees C hybridization temperature. Coupling of heated electrodes and highly
      sensitive electrochemical DNA hybridization detection methods should enhance
      detection limits of the latter significantly.

PMID- 16089393
TI  - Synthesis of ferrocene-grafted poly(p-phenylene-ethynylenes) and control of
      electrochemical behaviors of their thin films.
AB  - New ferrocene-coated poly(p-phenylene-ethynylenes) (PPEs) with end capping groups
      of protected thiol were prepared by a palladium-catalyzed Sonogashira coupling
      reaction. Ferrocene groups were covalently attached to polymers A and B through
      ethylene oxide tethers and to polymer C through methylene tethers. Polymers A and
      B are soluble in common solvents such as tetrahydrofuran (THF), chloroform,
      methylene chloride, acetone, dimethylformamide (DMF), and dimethyl sulfoxide
      (DMSO), and polymer C is soluble in toluene, THF, chloroform, and methylene
      chloride. Polymers A-C display low quantum yield, caused by electron-transfer
      quenching of ferrocene groups as electron donors. The polymer thin films were
      prepared through incubation of gold electrodes in THF solutions containing the
      polymers for 2 days. Ferrocene in thin films of polymers A and B display
      significantly faster electron-transfer rate than that of polymer C. Hydrophilic
      ethylene oxide side chains of polymers A and B decrease formal potential of
      tethered ferrocene groups because of electron-donating effect from ethylene oxide
      side chains, which stabilizes the ferrocenium ion and leads to a cathodic shift
      of the redox wave.

PMID- 16089392
TI  - Layer by layer self-assembled polyelectrolyte multilayers with embedded
      phospholipid vesicles obtained by spraying: integrity of the vesicles.
AB  - In a previous paper (Michel, M.; Vautier, D.; Voegel, J.-C.; Schaaf, P.; Ball, V.
      Langmuir 2004, 20, 4835), we showed that phospholipid vesicles can be
      incorporated into poly(glutamic-acid)/poly(allylamine) (PGA/PAH) multilayered
      polyelectrolyte films built by the alternated dipping of a surface in polyanion
      and polycation solutions. AFM imaging, quartz crystal microbalance, and
      ellipsometry suggested that the vesicles remain intact when adhering on the
      surface. In the present paper, we show that such films can also be realized by
      spraying both the polyelectrolyte solutions and the vesicles onto the surface.
      Using such vesicles filled with ferrocyanide ions, we prove by cyclic voltammetry
      that the sprayed vesicles remain intact when embedded in the multilayers. We show
      that multilayers containing two distinct layers of intact vesicles separated by
      several polyanion/polycation bilayers can also be constructed. Polyelectrolyte
      multilayers containing layers of phospholipid vesicles could act as reservoirs
      for drug or other biologically active molecules in controlled release bioactive
      coatings.

PMID- 16089394
TI  - Multivalent dendrimers at molecular printboards: influence of dendrimer structure
      on binding strength and stoichiometry and their electrochemically induced
      desorption.
AB  - A fundamental understanding of multivalency can have a profound influence on
      bottom-up nanofabrication. For this purpose, three different types of ferrocenyl
      (Fc) functionalized dendrimers of generations 1-5 with various spacer groups were
      adsorbed at self-assembled monolayers (SAMs) of heptathioether-functionalized
      beta-cyclodextrin (betaCD) on gold. The dendrimers formed kinetically stable
      supramolecular assemblies at the betaCD host surface having up to eight
      multivalent supramolecular interactions, but could be efficiently removed from
      the host surface by electrochemical oxidation of the Fc end groups. Dendrimer
      desorption and re-adsorption could be repeated a number of times without
      significant decomposition of the system. The stoichiometries of the dendrimers at
      the surface were determined using cyclic voltammetry (CV). These were
      quantitatively confirmed for the lower generations by surface plasmon resonance
      (SPR) titrations of the dendrimers to the betaCD SAM. Measuring CV and SPR
      simultaneously gave crucial mechanistic information on the electrochemically
      induced desorption of the dendrimers from the host surface. The redox-active
      dendrimers effectively blocked the host surface for binding other molecules, e.g.
      adamantyl-functionalized dendrimers, but electrochemically induced release of the
      blocking layer revealed the host surface to which the adamantyl dendrimers could
      then bind.

PMID- 16089395
TI  - Surface immobilized protein multilayers for cell seeding.
AB  - Multilayer assemblies containing various cell-adhesive proteins such as gelatin,
      collagen IV, and laminin or polycations polylysine and poly(ethyleneimine) were
      immobilized on the polystyrene surface using the layer-by-layer technique based
      on hydrophobic and electrostatic interactions between oppositely charged
      macromolecules. The formation and stability of the assemblies and the adsorption
      of proteins from a serum containing cell-cultivation media onto their surfaces
      were observed in real time by Fourier transform infrared multiple internal
      reflection spectroscopy. The adhesion and growth of mouse embryonic stem cells
      line D3 were tested in polystyrene culture dishes coated with the assemblies. The
      cells were seeded in complete serum-containing media or in serum-free media and
      in the presence (non-differentiated) and/or absence (differentiated) of leukemia
      inhibitory factor. Proteins from serum-containing cell-cultivation media adsorbed
      rapidly onto positively charged surfaces. The cells grew best on surfaces coated
      with gelatin and collagen IV assemblies. There were no significant differences in
      the growth of the non-differentiated and differentiated cells in complete serum
      containing media. When seeded in serum-free media, non-differentiated cells grew
      better than the differentiated ones. Particularly, polycation surfaces treated
      with glutaraldehyde promoted the growth of the non-differentiated cells and
      hindered the growth of the differentiated cells. The layer-by-layer deposition
      appears to be a practicable technique by which scaffolds for tissue engineering
      can be coated with biomolecular assemblies tailored to specific cells and
      applications.

PMID- 16089396
TI  - Formation of aminosilane-functionalized mica for atomic force microscopy imaging
      of DNA.
AB  - Factors affecting the functionalization of mica with aminosilanes, in particular,
      aminopropyltriethoxysilane (APTES-mica), formed from the vapor phase have been
      systematically studied. The relative humidity (RH) during vapor deposition has
      been varied, and postdeposition treatment through baking has been used, as well
      as the comparison of mono and trifunctionality, to investigate how optimal
      surfaces for AFM imaging of DNA are formed. It is found that the stability of the
      APTES layers is a consequence of lateral polymerization and not covalent
      attachment to the mica substrate. At low RH (<25%), DNA adopts an open, well
      resolved conformation, whereas at >25% RH, DNA surface-induced condensation
      occurs. Contact mode AFM scratching experiments show that two main structures of
      the silane layer exist at different humidity: a monolayer exists at RH < 25%, and
      a bilayer structure exists at RH > 25%. Finally, structural changes that these
      two layer types undergo after baking at 150 degrees C were investigated by AFM
      and X-ray photoelectron spectroscopy (XPS), and these now prevented DNA from
      binding to the APTES-mica, except in the presence of Mg(II) ions.

PMID- 16089397
TI  - Architecture and high-resolution structure of Bacillus thuringiensis and Bacillus
      cereus spore coat surfaces.
AB  - We have utilized atomic force microscopy (AFM) to visualize the native surface
      topography and ultrastructure of Bacillus thuringiensis and Bacillus cereus
      spores in water and in air. AFM was able to resolve the nanostructure of the
      exosporium and three distinctive classes of appendages. Removal of the exosporium
      exposed either a hexagonal honeycomb layer (B. thuringiensis) or a rodlet outer
      spore coat layer (B. cereus). Removal of the rodlet structure from B. cereus
      spores revealed an underlying honeycomb layer similar to that observed with B.
      thuringiensis spores. The periodicity of the rodlet structure on the outer spore
      coat of B. cereus was approximately 8 nm, and the length of the rodlets was
      limited to the cross-patched domain structure of this layer to approximately 200
      nm. The lattice constant of the honeycomb structures was approximately 9 nm for
      both B. cereus and B. thuringiensis spores. Both honeycomb structures were
      composed of multiple, disoriented domains with distinct boundaries. Our results
      demonstrate that variations in storage and preparation procedures result in
      architectural changes in individual spore surfaces, which establish AFM as a
      useful tool for evaluation of preparation and processing "fingerprints" of
      bacterial spores. These results establish that high-resolution AFM has the
      capacity to reveal species-specific assembly and nanometer scale structure of
      spore surfaces. These species-specific spore surface structural variations are
      correlated with sequence divergences in a spore core structural protein SspE.

PMID- 16089399
TI  - Biomimetics with a self-assembled monolayer of catalytically active tethered
      isoalloxazine on Au.
AB  - A new biomimetic nanostructured electrocatalyst comprised of a self-assembled
      monolayer (SAM) of flavin covalently attached to Au by reaction of
      methylformylisoalloxazine with chemisorbed cysteamine is introduced. Examinations
      by Fourier transform infrared spectroscopy and scanning tunneling microscopy
      (STM) show that the flavin molecules are oriented perpendicular to the surface
      with a 2 nm separation between flavin molecules. As a result of the contrast
      observed in the STM profiles between areas only covered by unreacted cysteamine
      and those covered by flavin-cysteamine moieties, it can be seen that the flavin
      molecules rise 0.7 nm above the chemisorbed cysteamines. The SAM flavin
      electrocatalyst undergoes fast electron transfer with the underlying Au and shows
      activity toward the oxidation of enzymatically active beta-NADH at pH 7 and very
      low potential (-0.2 V vs Ag/AgCl), a requirement for use in an enzymatic biofuel
      cell, and a 100-fold increase in activity with respect to the collisional
      reaction in solution.

PMID- 16089398
TI  - Determining the conformation of an adsorbed Br-PEG-peptide by long period X-ray
      standing wave fluorescence.
AB  - Long-period X-ray standing wave fluorescence (XSW) and X-ray reflectivity
      techniques are employed to probe the conformation of a Br-poly(ethylene glycol)
      (PEG)-peptide adsorbate at the hydrated interface of a polystyrene substrate. The
      Br atom on this Br-PEG-peptide construct serves as a marker atom allowing
      determination by XSW of its position and distribution with respect to the
      adsorption surface with angstrom resolution. Adsorption occurs on native or ion
      beam-modified polystyrene films that are spin-coated onto a Si substrate and
      display either nonpolar or polar surfaces, respectively. A compact, oriented
      monolayer of Br-PEG-peptide can be formed with the peptide end adsorbed onto the
      polar surface and the PEG end terminating with the Br tag extending into the
      aqueous phase. The 108-141 A distance of the Br atom from the polystyrene surface
      in this oriented monolayer is similar to the estimated approximately 150 A length
      of the extended Br-PEG-peptide. This Br-polystyrene distance depends on
      adsorption time and surface properties prior to adsorption. Incomplete
      multilayers form on the polar surface after sufficient adsorption time elapses.
      By contrast, adsorption onto the nonpolar surface is submonolayer, patchy, and
      highly disordered with an isotropic Br distribution. Overall, this combination of
      X-ray surface scattering techniques with a novel sample preparation strategy has
      several advantages as a real space probe of adsorbed or covalently bound
      biomolecules at the liquid-solid interface.

PMID- 16089401
TI  - Spatial modulation in cross-linked binary polymer blends.
AB  - Spatial modulation means that the free energy of the composite mixture is
      minimized at a finite wavenumber, which defines the primary length scale, the
      maximum size possible, of the evolving phases. Although spatial modulation may
      appear in different systems in different ways and is not necessarily a
      thermodynamic precept, here it is expressed as a thermodynamic consequence of
      short-range interfacial forces pitted against long-range elastic forces. Cross
      linked chains bring about new thermodynamic interactions based on their
      conformations and the fractal dimensions of the chain networks to which they
      tether and belong. Interplay among these different interactions during phase
      ordering brings about the spatial modulation and the spatial pattern. Here, the
      underlying processes are only succinctly outlined.

PMID- 16089400
TI  - Interaction of cationic lipid vesicles with model cell membranes--as determined
      by neutron reflectivity.
AB  - Transfection of cells by DNA (for the purposes of gene therapy) can be
      effectively engineered through the use of cationic lipid/DNA "lipoplexes",
      although the transfection efficiency of these lipoplexes is sensitive to the
      neutral "helper" lipid included. Here, neutron reflectivity has been used to
      investigate the role of the helper lipid present during the interaction of
      cationic lipid vesicles with model cell membranes. Dimethyldioctadecylammonium
      bromide (DDAB) vesicles were formed with two different helper lipids, 1,2
      dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) and cholesterol, and the
      interaction of these vesicles with a supported phospholipid bilayer was
      determined. DOPE-containing vesicles were found to interact faster with the
      membrane than those containing cholesterol, and vesicles containing either of the
      neutral helper lipids were found to interact faster than when DDAB alone was
      present. The interaction between the vesicles and the membrane was characterized
      by an exchange of lipid between the membrane and the lipid aggregates in
      solution; the deposition of vesicle bilayers on the surface of the membrane was
      not apparent.

PMID- 16089402
TI  - Porous tin oxide nanostructured microspheres for sensor applications.
AB  - We have sought to enhance the sensitivity of conductometric gas microsensors
      through the design and fabrication of porous, three-dimensional tin oxide
      nanoparticle structures. Electrostatically controlled layer-by-layer processing
      in aqueous solutions was used to decorate sacrificial latex microspheres with
      Sb:SnO2 nanoparticles. To evaluate their sensing performance, these structures
      were then deposited as films, via micropipetting, on MEMS micro-hot-plate
      platforms with interdigitated electrodes. Prior to gas testing, rapid heating of
      the micro-hot-plates was used to remove the sacrificial latex templates, thereby
      revealing a 3-D structure composed of interconnected spherical tin oxide
      nanoparticle shells with porous ultrathin walls. Changes in film conductance,
      caused by exposure to test gases (methanol, carbon monoxide, benzene, water) in a
      dry air background, were measured at different temperatures. Hollow nanoparticle
      microsphere films exhibited partial selectivity for these different gases, good
      dynamic range at different temperatures and gas concentrations, and good
      repeatability and stability over long runs. These films also yielded
      approximately 3-fold and 5-fold increases in sensitivity to methanol when
      compared to SnO2 polycrystalline chemical vapor deposition films and Sb:SnO2
      microporous nanoparticle films, respectively. Gains in sensitivity are attributed
      to the multiscale porous architecture of the hollow microsphere films. This
      architecture promotes gas diffusion and increases the active surface area.

PMID- 16089403
TI  - Fabricating and aligning pi-conjugated polymer-functionalized DNA nanowires:
      atomic force microscopic and scanning near-field optical microscopic studies.
AB  - We report a simple method to functionalize DNA with pi-conjugated polymer,
      forming highly aligned and integrated arrays of pi-conjugated polymer nanowires
      of a few nanometers diameter. pi-conjugated polymer, polyphenazasiline, having
      alkylammonium salts on the N atom (PPhenaz-TMA), synthesized in this study can be
      directly attached to DNA, which can be organized along stretched and aligned DNA
      molecules on surfaces as a template. Furthermore, PPhenaz-TMA/DNA nanowires were
      stretched and aligned on surfaces, even when PPhenaz-TMA/DNA complexes formed in
      solutions. The resulting PPhenaz-TMA/DNA nanowires could be easily converted to
      oxidized states or metallic nanowires by using adequate oxidant or metal salts.
      The direct visualization of PPhenaz-TMA/DNA nanowires and its structural changes
      have been studied by atomic force microscopy and scanning near-field optical
      microscopy.

PMID- 16089404
TI  - Gold and silver uptake and nanoprecipitation on calcium alginate beads.
AB  - Calcium alginate beads were investigated for their biosorption performance in the
      removal of gold and silver from aqueous solutions. It was found that uptake
      capacities were significantly affected by the solution pH, with optimum pH values
      of 2 and 4 for gold and silver, respectively. Kinetic and isotherm experiments
      were carried out at the optimum pH. The maximum uptake capacities were 290 mg/g
      for Au and 52 mg/g for Ag. FTIR analysis indicated that both carboxylic and
      hydroxylic functional groups in alginate beads are involved in the metal binding
      and later reduction of gold (+3) and silver (+1) to gold (0) and silver (0). SEM
      and X-ray diffraction confirmed the formation of gold and silver nanoparticles.

PMID- 16089405
TI  - Diverse spreading behavior of binary polymer nanodroplets.
AB  - Molecular dynamics simulations are used to study the spreading of binary polymer
      nanodroplets in a cylindrical geometry. The polymers, described by the bead
      spring model, spread on a flat surface with a surface-coupled Langevin thermostat
      to mimic the effects of a corrugated surface. Each droplet consists of chains of
      length 10 or 100 monomers with approximately 350,000 monomers total. The
      qualitative features of the spreading dynamics are presented for differences in
      chain length, surface interaction strength, and composition. When the components
      of the droplet differ only in the surface interaction strength, the more strongly
      wetting component forms a monolayer film on the surface even when both materials
      are above or below the wetting transition. In the case where the only difference
      is the polymer chain length, the monolayer film beneath the droplet is composed
      of an equal amount of short chain and long chain monomers even when one component
      (the shorter chain length) is above the wetting transition and the other is not.
      The fraction of short and long chains in the precursor foot depends on whether
      both the short and the long chains are in the wetting regime. Diluting the
      concentration of the strongly wetting component in a mixture with a weakly
      wetting component decreases the rate of diffusion of the wetting material from
      the bulk to the surface and limits the spreading rate of the precursor foot, but
      the bulk spreading rate actually increases when both components are present. This
      may be due to the strongly wetting material pushing out the weakly wetting
      material as it moves toward the precursor foot.

PMID- 16089406
TI  - Fabrication of a metal nanoparticles and polymer nanofibers composite material by
      an in situ chemical synthetic route.
AB  - This work demonstrated a facile route for the synthesis of poly(3,5-dimethyl
      aniline) nanofibers by polymerization of 3,5-dimethyl aniline using Pd-acetate as
      the oxidant. The reduction of Pd ion is accompanied by oxidative polymerization
      of 3,5-dimethyl aniline, leading to a metal-polymer composite material. Palladium
      nanoparticles (approximately 2 nm) are uniformly distributed throughout the
      polymer that makes the composite material a unique morphology. The resultant
      composite material was characterized by means of different techniques. IR and
      Raman spectra provide the information on the chemical structure of the polymer.
      TEM images show the morphology of the polymer and size of the metal particles.

PMID- 16089407
TI  - Morphology-driven surface segregation in a blend of poly(epsilon-caprolactone)
      and poly(vinyl chloride).
AB  - A blend of poly(epsilon-caprolactone) (PCL) and poly(vinyl chloride) (PVC) with
      90 wt % PCL was prepared. Two films of this blend, which were grown at 35 and 45
      degrees C, showed the absence and presence of banded spherulites, respectively. A
      detailed examination conducted with time-of-flight secondary ion mass
      spectrometry (ToF-SIMS) found that the surface composition of the film grown at
      45 degrees C was related to its structure, which was shown to contain ridges and
      valleys. Phase images obtained using atomic force microscopy (AFM) indicated that
      the ridges and valleys consisted of edge-on and flat-on lamellae, respectively.
      ToF-SIMS imaging revealed that PVC and PCL were located mainly on the surface of
      the valleys and ridges, respectively. This morphology-driven surface segregation
      was caused by the difference in the surface energy between the flat-on and edge
      on lamellae.

PMID- 16089408
TI  - Numerical and experimental study of critical roof collapse conditions in soft
      lithography.
AB  - One of the major issues during soft lithographic processes is that, if the
      pressing force on the stamp becomes too high, the stamp may erroneously come into
      contact with the substrate in zones where contact is not intended. This decreases
      the patterning accuracy and may lead to badly or nonperforming electronic devices
      and is therefore undesired. Design rules, available at an early stage in the
      design phase, are desired to speed-up the development of this technique.
      Ultimately, these rules should give an indication of the critical pressure that
      can safely be applied on the stamp thereby avoiding unwanted contact between the
      stamp and the substrate. To obtain these critical pressures, numerical analyses
      of the deformation behavior of two characteristic configurations in the
      microstructured surface pattern of the rubber stamp are performed. The
      deformation behavior of the rubber is modeled according to a Gaussian and a non
      Gaussian approach, leading to a neo-Hookean and Arruda-Boyce constitutive model,
      respectively. Besides these material nonlinearities, geometrical nonlinearities
      are taken into account as well. The calculated pressure at which undesired
      contact takes place (the roof collapse pressure) is compared to experimentally
      obtained values for two particular types of structures, and the results are in
      agreement within the error margins of the experiments and those ensuing from the
      assumptions of the numerical simulations.

PMID- 16089409
TI  - Gold nanoparticle networks with photoresponsive interparticle spacings.
AB  - Photoresponsive gold nanoparticle networks were prepared by functionalizing them
      with azobenzene derivatives. A network can be formed when a linker molecule
      constituting the azobenzene moiety suitably derivatized on either side with gold
      surface sensitive groups such as thiols and amines is added to the nanoparticle
      solution. It is shown that the interparticle spacing in the networks could be
      controlled by the reversible trans-cis isomerization of the azobenzene moiety
      induced by UV and visible light, respectively. The photoinduced variation in the
      interparticle spacings is inferred by the changes in the optical spectra of the
      gold nanoparticles which display a red or blue shift in the surface plasmon
      resonance peak depending on a decrease or increase in the interparticle spacing,
      respectively. Transmission electron microscopy images are in consonance with the
      evidence from the optical spectra.

PMID- 16089410
TI  - Nonspecific interactions of a carboxylate-substituted PPE with proteins. A
      cautionary tale for biosensor applications.
AB  - Two carboxylate-substituted, fluorescent (Phi = 0.08), water-soluble poly(p
      phenyleneethynylene)s (PPE) and a water-soluble model compound were exposed to a
      series of proteins and bovine serum. While the anionic PPEs do not have any
      specific binding sites, they form stable complexes with histone, lysozyme,
      myoglobin, and hemoglobin. The complex formation was evidenced by fluorescence
      quenching. Bovine serum albumin does not quench the fluorescence of the PPEs but
      enhances it, probably due to its surfactant character. These results imply that
      the use of charged conjugated polymers as biosensors, while an attractive
      proposition, has to take into account strong nonspecific interactions between
      conjugated polymers and the host of proteins that is found in cells and complex
      biological fluids.

PMID- 16089411
TI  - Effects of sonication on the size and crystallinity of stable zwitterionic
      organic nanoparticles formed by reprecipitation in water.
AB  - Nanoparticles of a novel organic zwitterionic Meisenheimer complex, N',N' ',N' ''
      tri(isopropyl)-4-oxo-6-(isopropyliminio)-2-s-(2H)triazinespiro-1'-2',4',6'
      trinitrocyclohexadienylide, were synthesized by reprecipitation in water under
      different conditions. While reprecipitation alone resulted in a suspension of
      amorphous particles that fell out of solution within hours, sonication for
      different periods of time resulted in the formation of crystalline particles that
      were stable in solution over the course of weeks. The disk-shaped particles had
      an average diameter of 140 nm and a thickness of 70 nm. Comparison of the optical
      spectroscopy of these particles with the monomer indicates that they possess
      delocalized excitonic states and enhanced radiative decay rates. The use of
      zwitterionic molecules in conjunction with sonication provides a way to exert
      some level of control over particle size and morphology, as well as increased
      colloidal stability.

PMID- 16089412
TI  - Star-block copolymers as templates for the preparation of stable gold
      nanoparticles.
AB  - Gold nanoparticles of improved stability against aggregation were prepared using
      poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) star-block
      copolymers. A five-arm star-shaped macroinitiator (PEO) was utilized for the
      automated parallel controlled ring-opening polymerization of epsilon-caprolactone
      to prepare a series of PEO-b-PCL star-block copolymers with a constant PEO core
      linked to PCL blocks of variable length. The PEO core was swelled with KAuCl4 in
      N,N-dimethylformamide (DMF), and gold nanoparticles were subsequently obtained by
      reduction with NaBH4. Since the process was always templated by the same PEO core
      for all investigated polymers, the average dimension of the formed gold
      nanoparticles was in the same range for all star-block copolymers. In sharp
      contrast, the size distribution and long-term stability against aggregation of
      the gold nanoparticles dispersed in DMF were strongly dependent on the PCL block
      length, confirming the role of PCL blocks as stabilizing blocks for these
      nanoparticles.

PMID- 16089413
TI  - Kinetic studies on the sulfate radical-initiated polymerization of vinyl acetate
      and 4-vinyl pyridine in the presence of silica nanoparticles.
AB  - The photolysis of silica suspensions of pH approximately 8 containing
      peroxodisulfate ions leads to the generation of two "surface transients" with a
      distinct spectrum and reactivity. Time-resolved and continuous irradiation
      experiments of similar dispersions also containing variable concentrations of
      vinyl acetate (VA) or 4-vinyl pyridine (4-VP) allowed the evaluation of the
      contribution of silica/water interfacial reactions to the kinetics and structural
      pattern of polymers synthesized using sulfate radicals as initiators. The rate
      constants measured for the reactions of the surface transients with 4-VP are 1
      order of magnitude higher than those of VA, despite the fact that both species
      show similar reactivity in homogeneous solution toward sulfate radicals. It is
      suggested that both the sorption capacity and the different specific interactions
      with the silica surface of 4-VP and VA contribute to the observed reaction rates.
      Micrometer-sized latex particles of 4-VP and VP showed higher stability and more
      homogeneous size distributions when obtained in the presence of silica
      nanoparticles. Under the experimental conditions required for obtaining polymer
      particles, both the contribution of the described interfacial reactions and the
      effect of silica adsorbed monomer on the initiation steps of the polymerization
      may be neglected. The importance of in situ adsorption of the oligomer/polymer
      chains to silica NP during the polymerization propagation steps in determining
      the particle morphology is discussed.

PMID- 16089414
TI  - Physical properties of aqueous solutions of a thermo-responsive neutral copolymer
      and an anionic surfactant: turbidity and small-angle neutron scattering studies.
AB  - Aqueous mixtures of the anionic sodium dodecyl sulfate (SDS) surfactant and
      thermo-responsive poly(N-vinylcaprolactam) chains grafted with omega-methoxy
      poly(ethylene oxide) undecyl alpha-methacrylate (PVCL-g-C11EO42) have been
      characterized using turbidimetry and small-angle neutron scattering (SANS).
      Turbidity measurements show that the addition of SDS to a dilute aqueous
      copolymer solution (1.0 wt %) induces an increase of the cloud point (CP) value
      and a decrease of the turbidity at high temperatures. In parallel, SANS results
      show a decrease of both the average distance between chains and the global size
      of the objects in solution at high temperatures as the SDS concentration is
      increased. Combination of these findings reveals that the presence of SDS in the
      PVCL-g-C11EO42 solutions (1.0 wt %) promotes the formation of smaller aggregates
      and, consequently, leads to a more homogeneous distribution of the chains in
      solution upon heating of the mixtures. Moreover, the SANS data results show that
      the internal structure of the formed aggregates becomes more swollen as the SDS
      concentration increases. On the other hand, the addition of moderate amounts of
      SDS (up to 4 mm) to a semidilute copolymer solution (5.0 wt %) gives rise to a
      more pronounced aggregation as the temperature rises; turbidity and SANS studies
      reveal in this case a decrease of the CP value and an increase of the scattered
      intensity at low q. The overall picture that emerges from this study is that the
      degree of aggregation can be accurately tuned by varying parameters such as the
      temperature, level of surfactant addition, and polymer concentration.

PMID- 16089415
TI  - Spontaneous formation of gold nanoparticles in poly(ethylene oxide)
      poly(propylene oxide) solutions: solvent quality and polymer structure effects.
AB  - We report here on the effects that the solution properties of poly(ethylene
      oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers have on the
      reduction of hydrogen tetrachloroaurate(III) hydrate (HAuCl4.3H2O) and the size
      of gold nanoparticles produced. The amphiphilic block copolymer solution
      properties were modulated by varying the temperature and solvent quality (water,
      formamide, and their mixtures). We identified two main factors, (i) block
      copolymer conformation or structure (e.g., loops vs entanglements, nonassociated
      polymers vs micelles) and (ii) interactions between AuCl4- ions and block
      copolymers (attractive ion-dipole interactions vs repulsive interactions due to
      hydrophobicity), to be important for controlling the competition between the
      reactivities of AuCl4- reduction in the bulk solution to form gold seeds and on
      the surface of gold seeds (particles) and the particle size determination. The
      particle size increase observed with increased temperature in aqueous solutions
      is attributed to enhanced hydrophobicity of the block copolymer, which favors
      AuCl4- reduction on the surface of seeds. The lower reactivity and higher
      particle sizes observed in formamide solutions are attributed to the shielding of
      ion-dipole interaction between AuCl4- ions and block copolymers by formamide,
      which overcomes the beneficial effects of formamide on the block copolymer
      conformation (lower micelle concentration).

PMID- 16089416
TI  - Preparation of visible-light-responsive TiO2-xNx photocatalyst by a sol-gel
      method: analysis of the active center on TiO2 that reacts with NH3.
AB  - Active reaction centers for ammonia on titanium oxyhydroxide were explored to
      direct the search for an efficient sol-gel method for the synthesis of a titanium
      oxynitride (TiO2-xNx) sample with an efficient responsiveness to the visible
      light constituting a main part of the solar spectrum. The results lead to the
      conclusion that the site giving IR bands at around 2195 cm(-1) for the adsorbed
      CO molecules at 300 K is a reactive site and behaves as Lewis acid site in the
      coordination environment of distorted five-coordinate Ti4+ ions. Ammonia
      molecules are adsorbed on such a site to form -NH2 and -OH species during the
      heat treatments at a temperature above 373 K, and they are ultimately
      incorporated into the TiO2 lattice as nitride through the dehydration at higher
      temperatures of up to 723 K, resulting in the formation of an anatase type of
      TiO2-xNx.

PMID- 16089417
TI  - Fabrication and photocatalytic characterizations of ordered nanoporous X-doped (X
      = N, C, S, Ru, Te, and Si) TiO2/Al2O3 films on ITO/glass.
AB  - Transparent, ordered nanoporous TiO2/Al2O3 composite films doped with metal
      elements (Ru, Si, and Te) and nonmetal elements (N, C, and S) were fabricated by
      successive anodization and sol-gel process directly on glass substrates covered
      with a tin-doped indium oxide (ITO) film. The doping of ruthenium, nitrogen,
      carbon, and sulfur in TiO2 exhibited an enhanced effect on the absorbance, while
      the doping of silicon and tellurium showed little effect. Particularly, the N-
      and Ru-doped TiO2/Al2O3 films on ITO/glass developed an enhanced absorption red
      shift of 580 nm (-N) and 500 nm (-Ru). The nanoporous TiO2/Al2O3 composite film
      exhibited the highest photocatalytic activity in decomposing acetaldehyde under
      ultraviolet-light irradiation, with a value of 13 times in initial reaction rate
      or 7.8 times in quantum yield higher than a commercially available TiO2 material,
      Degussa P25. The ultraviolet-light photocatalytic activities of nanoporous
      TiO2/Al2O3 films were enhanced by the doping of nitrogen, carbon, and sulfur but
      slightly weakened by the doping of ruthenium, silicon, and tellurium.
      Particularly, the nanoporous N-doped TiO2/Al2O3 films exhibited effective
      photocatalytic activity on ultraviolet light decomposition of a highly toxic
      dioxin, HpCDD, and gave the highest decomposition rate of approximately 95% (via
      7 h of irradiation) for the specimen with a dopant content of 1.7 wt % nitrogen.

PMID- 16089418
TI  - Micropore to macropore structure-designed silicas with regulated condensation of
      silicic acid nanoparticles.
AB  - A new preparation method for porous silica particles was developed using
      activated silica sols which are called nano-silica solutions in this paper.
      Several kinds of organic and inorganic acids are employed to neutralize diluted
      sodium silicate solutions to form the nano-silica solutions: formic acid, acetic
      acid, propionic acid, oxalic acid, succinic acid, dl-malic acid, citric acid, and
      tricarballylic acid as carboxylic acids, and sulfuric acid and hydrochloric acid
      as inorganic acids. The effect of salts in the nano-silica solution is also
      studied. The products were investigated using a field emission scanning electron
      microscope, an X-ray diffractometer, the nitrogen adsorption technique, and a
      mercury porosimeter. Microporous silicas were produced when carboxylic acids were
      applied; the formation of micropores was influenced by the pH of the nano-silica
      solutions and molecular sizes of the carboxylic acids. Addition of a salt in a
      citric acid solution increased the mesopore volume. Macropores were formed when
      inorganic acids including salts were applied; the salt nanoparticles which were
      crystallized in silica spheres acted as templates. The anion types and salt
      concentrations in the nano-silica solutions affected the aggregation condition of
      silica nanoparticles, following the Schulze-Hardy rule.

PMID- 16089419
TI  - Flow behavior of colloidal rodlike viruses in the nematic phase.
AB  - The behavior of a colloidal suspension of rodlike fd viruses in the nematic
      phase, subjected to steady state and transient shear flows, is studied. The
      monodisperse nature of these rods combined with relatively small textural
      contribution to the overall stress make this a suitable model system to
      investigate the effects of flow on the nonequilibrium phase diagram. Transient
      rheological experiments are used to determine the critical shear rates at which
      director tumbling, wagging, and flow-aligning occurs. The present model system
      enables us to study the effect of rod concentration on these transitions. The
      results are in quantitatively agreement with the Doi-Edwards-Hess model.
      Moreover, we observe that there is a strong connection between the dynamic
      transitions and structure formation, which is not incorporated in theory.

PMID- 16089420
TI  - Stamp collapse in soft lithography.
AB  - We have studied the so-called roof collapse in soft lithography. Roof collapse is
      due to the adhesion between the PDMS stamp and substrate, and it may affect the
      quality of soft lithography. Our analysis accounts for the interactions of
      multiple punches and the effect of elastic mismatch between the PDMS stamp and
      substrate. A scaling law among the stamp modulus, punch height and spacing, and
      work of adhesion between the stamp and substrate is established. Such a scaling
      law leads to a simple criterion against the unwanted roof collapse. The present
      study agrees well with the experimental data.

PMID- 16089421
TI  - Evolution of mechanical response of sodium montmorillonite interlayer with
      increasing hydration by molecular dynamics.
AB  - The mechanical response of the interlayer of hydrated montmorillonite was
      evaluated using steered molecular dynamics. An atomic model of the sodium
      montmorillonite was previously constructed. In the current study, the interlayer
      of the model was hydrated with multiple layers of water. Using steered molecular
      dynamics, external forces were applied to individual atoms of the clay surface,
      and the response of the model was studied. The displacement versus applied stress
      and stress versus strain relationships of various parts of the interlayer were
      studied. The paper describes the construction of the model, the simulation
      procedure, and results of the simulations. Some results of the previous work are
      further interpreted in the light of the current research. The simulations provide
      quantitative stress deformation relationships as well as an insight into the
      molecular interactions taking place between the clay surface and interlayer water
      and cations.

PMID- 16089422
TI  - Direct probe of iron vibrations elucidates NO activation of heme proteins.
AB  - We use nuclear resonance vibrational spectroscopy (NRVS) to identify the Fe-NO
      stretching frequency in the NO adduct of myoglobin (MbNO) and in the related six
      coordinate porphyrin Fe(TPP)(1-MeIm)(NO). Frequency shifts observed in MbNO Raman
      spectra upon isotopic substitution of Fe or the nitrosyl nitrogen confirm and
      extend the NRVS results. In contrast with previous assignments, the Fe-NO
      frequency of these six-coordinate complexes lies 70-100 cm-1 lower than in the
      analogous five-coordinate nitrosyl complexes, indicating a significant weakening
      of the Fe-NO bond in the presence of a trans imidazole ligand. This result
      supports proposed mechanisms for NO activation of heme proteins and underscores
      the value of NRVS as a direct probe of metal reactivity in complex biomolecules.

PMID- 16089423
TI  - Stereochemical assignment of intermediates in the rifamycin biosynthetic pathway
      by precursor-directed biosynthesis.
AB  - Natural and semisynthetic rifamycins are clinically important inhibitors of
      bacterial DNA-dependent RNA polymerase. Although the polyketide-nonribosomal
      peptide origin of the naphthalene core of rifamycin B is well established, the
      absolute and relative configuration of both stereocenters introduced by the first
      polyketide synthase module is obscured by aromatization of the naphthalene ring.
      To decode the stereochemistry of the rifamycin polyketide precursor, we
      synthesized all four diastereomers of the biosynthetic substrate for module 2 of
      the rifamycin synthetase in the form of their N-acetylcysteamine (SNAC)
      thioester. Only one diastereomer was turned over in vivo into rifamycin B, thus
      establishing the absolute and relative configuration of the native biosynthetic
      intermediates.

PMID- 16089424
TI  - CO2 as a supramolecular assembly agent: a route for lamellar materials with a
      high content of amine groups.
AB  - The uptake of carbon dioxide on N-(2-aminoethyl)-3-aminopropyltrimethoxysilane 1
      and N-(6-aminohexyl)-3-aminopropyltrimethoxysilane 2 afforded a supramolecular
      network of bis-silylated ammonium carbamate salts, the hydrolytic
      polycondensation of which gave rise to structured hybrid materials. Subsequent
      loss of CO2 was readily achieved upon heating, thus generating materials in which
      the structure was maintained (well-defined lamellar structure from 2) and
      contains free amino groups. The accessibility of amine-functionalized groups was
      shown by their ability to complex transition metal or lanthanide salts.

PMID- 16089425
TI  - Versatile diastereoselectivity in formal [3,3]-sigmatropic shifts of substituted
      1-alkenyl-3-alkylidenecyclobutanols and their silyl ethers.
AB  - A new method for the preparation of highly substituted cyclohexenones is
      reported. [2 + 2] Cycloaddition of 2-silyloxydienes with allenecarboxylate
      affords the 1-alkenyl-3-alkylidenecyclobutanol silyl ethers. Thermolysis of these
      compounds affords the methylene cyclohexenyl silyl ethers with excellent exo
      selectivity (>95:5) when monosubstituted alkenyl groups are used, while the use
      of disubstituted alkenyl groups gives generally low selectivity ( approximately
      2:1). However, rearrangement of the anion of the cyclobutanol (prepared by acidic
      hydrolysis of the TMS silyl ether) at low temperature gives the endo product with
      good to excellent diastereoselectivity (5-23:1). Two different mechanistic
      rationales are given for the two different processes: the first via a diradical
      and the second via a cleavage intramolecular Michael addition. Thus, the same
      starting material (e.g., 20) can be converted into either the exo or endo
      product, 22x or 22n, with good diastereocontrol by just changing the
      rearrangement conditions.

PMID- 16089426
TI  - Characterization of dynamics of perdeuterated proteins by MAS solid-state NMR.
AB  - We show in this communication that dynamic information for uniformly 2H,13C,15N
      isotopically enriched, crystalline proteins can be obtained by MAS solid-state
      NMR spectroscopy. The experiments make use of the deuterium quadrupolar tensor,
      which is the dominant interaction mechanism. Dynamic properties are accessed by
      measurement of the size of the quadrupolar coupling constant, Cq, and the value
      of the asymmetry parameter, eta, via evolution of the deuterium chemical shift,
      as well as by measurement of deuterium T1 relaxation times. Three-dimensional
      experiments are performed in order to obtain site-specific resolution. Due to
      proton dilution, no proton decoupling is required in the carbon evolution periods
      at MAS rotation frequencies of 10 kHz.

PMID- 16089427
TI  - Replication of a DNA microarray.
AB  - A mechanical method for efficient replication of DNA microarrays is described.
      The approach consists of three steps. First, a master DNA microarray consisting
      of single-stranded DNA elements is exposed to a solution containing the biotin
      functionalized complement of each array element. Following hybridization, a
      replica surface modified with streptavidin is brought into contact with the
      master. This results in linking of the biotin-functionalized complement with the
      replica surface. Next, the replica is separated from the master, and the
      complementary strands are transferred to the replica surface. The resulting
      complementary DNA microarray contains position-coded sequences that mirror the
      information contained on the master DNA microarray. Multiple replicas can be
      prepared from a single master, the replicas efficiently hybridize only their
      complement, and DNA not labeled with biotin is not transferred to the replica
      surface.

PMID- 16089428
TI  - Redox couples of inducible nitric oxide synthase.
AB  - We report direct electrochemistry of the iNOS heme domain in a DDAB film on the
      surface of a basal plane graphite electrode. Cyclic voltammetry reveals FeIII/II
      and FeII/I couples at -191 and -1049 mV (vs Ag/AgCl). Imidazole and carbon
      monoxide in solution shift the FeIII/II potential by +20 and +62 mV, while the
      addition of dioxygen results in large catalytic waves at the onset of FeIII
      reduction. Voltammetry at higher scan rates (with pH variations) reveals that the
      FeIII/II cathodic peak can be resolved into two components, which are
      attributable to FeIII/II couples of five- and six-coordinate hemes. Digital
      simulation of our experimental data implicates water dissociation from the heme
      as a gating mechanism for ET in iNOS.

PMID- 16089429
TI  - Excited-state structure determination of the green fluorescent protein
      chromophore.
AB  - Ultrafast polarization-sensitive infrared (IR) spectroscopy of the C=O stretching
      mode of the chromophore of the green fluorescent protein reveals a near complete
      twisting around the ethylenic bridge between the phenolate and imidazolidinone
      groups upon electronic excitation, hinting at a decisive role of this motion in
      the efficient internal conversion process.

PMID- 16089430
TI  - DNA-templated photoinduced silver deposition.
AB  - We are presenting a photography-derived methodology to achieve the photoreduction
      of Ag+-DNA complexes. lambda-Phage DNA was first loaded with silver ions, then
      irradiated with UV light at 254 nm. The DNA bases acted as light sensitizers,
      promoting the in situ reduction of Ag+ and the formation of metallic silver
      clusters. Three different approaches will illustrate this procedure, and silver
      nanoparticle chains will be grown along a DNA template in a rapid and specific
      way.

PMID- 16089431
TI  - Ti(IV) binds to human serum transferrin more tightly than does Fe(III).
AB  - The binding of titanium(IV) to human serum transferrin in 50 mM Tris with 20 mM
      bicarbonate and 10 mM citrate at pH 7.4 was studied by UV/vis kinetics and by
      isothermal titration calorimetry. Ti(IV) citrate, [Ti(C6H4O7)3]8-, employed in
      this study was previously characterized and delivers the metal to transferrin
      rapidly, allowing the quantification of the intrinsic binding constants for
      Ti(IV) to the C- and N-sites of transferrin. The results after correcting for
      blood plasma conditions (pH 7.4, [HCO3-] = 27 mM) reveal that Ti(IV) binds with
      greater affinity (log K = 26.8 and 25.7) than Fe(III) (log K = 22.5 and 21.4) to
      transferrin, a finding not previously observed for other examined metal ions. The
      strength of metal binding to transferrin correlates with the Lewis acidity of the
      metal. Ti(IV) is more Lewis acidic than Fe(III) and is nearly the same size. The
      study also reveals that Ti(IV) binds more tightly to one site than the other, and
      this difference is due to both entropic and enthalpic contributions. The study
      has implications for the role of transferrin in the anticancer activity of Ti(IV)
      drugs and the serum binding of Ti(IV) ions released from implants or imaging
      reagents.

PMID- 16089432
TI  - Time-resolved detection of melanin free radicals quenching reactive oxygen
      species.
AB  - Melanin, a ubiquitous, heterogeneous biological polymer composed of many
      different monomers, contains a population of stationary, intrinsic semiquinone
      like radicals. Additional extrinsic semiquinone-like radicals are reversibly
      photogenerated with visible or UV irradiation. The free radical chemistry of
      melanin is complex and not well characterized, especially the photochemistry of
      melanin in the presence of oxygen. To determine directly how melanin reacts in
      the presence of oxygen, time-resolved electron paramagnetic resonance (TREPR)
      spectroscopy was used to examine melanin free radical chemistry in human retinal
      pigment epithelium (RPE) cells under aerobic and anaerobic conditions. A TREPR
      difference spectrum was used to explore the nature of melanin chemistry in the
      presence of oxygen. The position and symmetrical line shape of the TREPR three
      dimensional difference spectrum shows that when reactive oxygen species (ROS) are
      scavenged, only one of the two or more chemically different melanin free radical
      species participates in ROS scavenging. This protective melanin radical species
      exists in both the extrinsic and intrinsic populations of melanin free radicals,
      allowing melanin to protect the RPE from toxic species in both the light and
      dark.

PMID- 16089433
TI  - A deep cavitand provides a structured environment for the Menschutkin reaction.
AB  - We report that a synthetic, vase-shaped host molecule forms complexes with
      quinuclidine and accelerates the Menschutkin reaction in the nanoenvironment that
      the host provides. Kinetic simulation is used to determine rate constants for
      reactions of the complex, and these are compared to control reactions in the
      absence of the host. The efficacy of the host in effecting this supramolecular
      acceleration is dependent on the structures of the alkylating agent and its
      leaving group.

PMID- 16089434
TI  - Selection of smart aptamers by equilibrium capillary electrophoresis of
      equilibrium mixtures (ECEEM).
AB  - We coin a term of "smart aptamers", which describes aptamers with predefined
      binding parameters of their interaction with the target. Here, we introduce a
      method for selection of smart aptamers with predefined values of Kd: equilibrium
      capillary electrophoresis of equilibrium mixtures (ECEEM). Conceptually, a
      mixture of a target with a DNA (RNA) library is prepared and equilibrated. A plug
      of the equilibrium mixture is injected into a capillary prefilled with a run
      buffer containing the target at the concentration identical to the target
      concentration in the equilibrium mixture. The components of the equilibrium
      mixture are separated by capillary electrophoresis while equilibrium is
      maintained between the target and aptamers. The unique feature of ECEEM is that
      aptamers with different Kd values migrate with different and predictable
      mobilities. Thus, collecting fractions with different mobilities results in smart
      aptamers with different and predefined Kd values. In this proof-of-principle
      work, we used ECEEM to select smart aptamers for MutS protein, for which aptamers
      have never been previously selected. Three rounds of ECEEM-based selection were
      sufficient to obtain smart aptamers with Kd values approaching theoretically
      predicted ones. ECEEM is the first method for aptamer selection whose ability to
      generate smart aptamers has been experimentally proven.

PMID- 16089435
TI  - Computational study of phosphatase activity in soluble epoxide hydrolase: high
      efficiency through a water bridge mediated proton shuttle.
AB  - Recently, a new branch of fatty acid metabolism has been opened by the novel
      phosphatase activity found in the N-terminal domain of the, hence bifunctional,
      soluble epoxide hydrolase (sEH). Importantly, this finding has also provided a
      new site for drug targeting in sEH's activity regulation. Classical MD and hybrid
      Car-Parrinello QM/MM calculations have been performed to investigate the reaction
      mechanism of the phosphoenzyme intermediate formation in the first step of the
      catalysis. The results support a concerted multi-event reaction mechanism: (1) a
      dissociative in-line nucleophilic substitution for the phosphoryl transfer
      reaction; (2) a double proton transfer involved in the formation of a good
      leaving group in the transition state. The presence of a water bridge in the
      substrate/enzyme complex allowed an efficient proton shuttle, showing its key
      role in speeding up the catalysis. The calculated free energy of the favored
      catalytic pathway is approximately 19 kcal/mol, in excellent agreement with
      experimental data.

PMID- 16089436
TI  - Self-cleavable stimulus responsive tags for protein purification without
      chromatography.
AB  - A simple method to purify recombinant proteins is described by fusing a target
      protein with an intein and an elastin-like polypeptide that only requires NaCl,
      dithiothreitol, and a syringe filter to isolate the target protein from
      Escherichia coli lysate. This tripartite fusion system enables rapid isolation of
      the target protein without the need for affinity chromatography for purification
      or proteases for cleavage of the target protein from the fusion. The elastin-like
      polypeptide tag imparts reversible phase transition behavior to the tripartite
      fusion so that the fusion protein can be selectively aggregated in cell lysate by
      the addition of NaCl. The aggregates are isolated by microfiltration and
      resolubilized by reversal of the phase transition in low ionic strength buffer.
      After resolubilizing the fusion protein, the intein is activated to cleave the
      target protein from the elastin-intein tag, and the target protein is then
      isolated from the elastin-intein fusion by an additional phase transition cycle.

PMID- 16089437
TI  - Force spectroscopy of quadruple H-bonded dimers by AFM: dynamic bond rupture and
      molecular time-temperature superposition.
AB  - We report on the application of the time-temperature superposition principle to
      supramolecular bond-rupture forces on the single-molecule level. The construction
      of force-loading rate master curves using atomic force microscopy (AFM)-based
      single-molecule force spectroscopy (SMFS) experiments carried out in situ at
      different temperatures allows one to extend the limited range of the
      experimentally accessible loading rates and hence to cross from thermodynamic
      nonequilibrium to quasi-equilibrium states. The approach is demonstrated for
      quadruple H-bonded ureido-4[1H]-pyrimidinone (UPy) moieties studied by variable
      temperature SMFS in organic media. The unbinding forces of single quadruple H
      bonding (UPy)2 complexes, which were identified based on a polymeric spacer
      strategy, were found to depend on the loading rate in the range of 5 nN/s to 500
      nN/s at 301 K in hexadecane. By contrast, these rupture forces were independent
      of the loading rate from 5 to 200 nN/s at 330 K. These results indicate that the
      unbinding behavior of individual supramolecular complexes can be directly probed
      under both thermodynamic nonequilibrium and quasi-equilibrium conditions. On the
      basis of the time-temperature superposition principle, a master curve was
      constructed for a reference temperature of 301 K, and the crossover force (from
      loading-rate independent to -dependent regimes) was determined as approximately
      145 pN (at a loading rate of approximately 5.6 nN/s). This approach significantly
      broadens the accessible loading-rate range and hence provides access to fine
      details of potential energy landscape of supramolecular complexes based on SMFS
      experiments.

PMID- 16089438
TI  - Selective recovery of dynamic guest structure in a nanoporous prussian blue
      through in situ X-ray diffraction: a differential pair distribution function
      analysis.
AB  - We use in situ X-ray diffraction to obtain data suitable for differential PDF
      analysis, providing unique insight into the structure of weakly bound, dynamic N2
      molecules in the Prussian blue system Mn3[Co(CN)6]2.x{N2}. The differential PDF
      shows a distributed orientation of N2 molecules constrained to sites centered
      about the (1/4,1/4,1/4) positions within the pores. The results show a subtle
      response of the framework to guest loading which corresponds principally to the
      perturbation of the Mn ion coordination.

PMID- 16089439
TI  - In vivo reporter labeling of proteins via metabolic delivery of coenzyme A
      analogues.
AB  - We demonstrate site-specific reporter labeling of proteins within live cells. By
      accessing the coenzyme A (CoA) metabolic pathway with a cell-permeable
      pantetheine analogue, we deliver CoA-bound reporter molecules for post
      translational protein modification in vivo. These methods may be applied to
      natural product pathway manipulation as well as applications in conventional
      molecular and cellular biology.

PMID- 16089440
TI  - Insulator-metal transition of intrinsic diamond.
AB  - Insulator-metal transitions are translations characterized by a sudden change in
      electron transport properties from localized to itinerant behavior of electrons.
      In most cases, it is detected in strongly disordered semiconductors as a function
      of temperature with statistically distributed donors and/or acceptors. Here, we
      show that reversible insulator-metal transitions take place in H-terminated
      intrinsic (undoped) single crystalline diamond, if immersed into redox
      electrolyte solutions at room temperature. The change is generated by valence
      band electrons of diamond, which tunnel into the redox-electrolyte, where they
      occupy empty electronic sites. We applied cyclic voltammetry experiments to
      characterize the insulator-metal transition in combination with different redox
      couples. The experiments show that transfer doping accounts for the
      experimentally detected phenomena, and that intrinsic diamond is a promising
      candidate for chemical sensing in a variety of applications.

PMID- 16089441
TI  - Unusual, promoted release of guests from amphiphilic cross-linked polymer
      networks.
AB  - Hyperbranched fluoropolymer-poly(ethylene glycol) (HBFP-PEG) cross-linked
      networks have been found to exhibit capabilities for the encapsulation of high
      levels of geraniol guest molecules coupled with unusually rapid release of the
      volatile compound. The promotion of the release of the volatile fragrance
      geraniol, observed as decreasing volatilization temperatures and increasing
      volatilization rates by thermogravimetric analyses, was found to be dependent
      upon the HBFP-PEG network composition, with increasing effects from decreasing wt
      % PEG and a maximum effect occurring at 5 wt % PEG.

PMID- 16089442
TI  - Cyanuric chloride as a mild and active Beckmann rearrangement catalyst.
AB  - The first general organocatalytic Beckmann rearrangement of ketoximes into amides
      has been realized by the catalytic use of cyanuric chloride. Furthermore, acids
      such as HCl and ZnCl2 are effective as cocatalysts with cyanuric chloride. For
      example, azacyclotridecan-2-one, which is synthetically useful as a starting
      material for nylon-12, was prepared in quantitative yield by the Beckmann
      rearrangement of cyclododecanone oxime (100 mmol scale) catalyzed by cyanuric
      chloride (0.5 mol %) and ZnCl2 (1 mol %).

PMID- 16089443
TI  - Carbon dioxide reduction and carbon monoxide activation employing a reactive
      uranium(III) complex.
AB  - The highly reactive, six-coordinate tris-aryloxide U(III) species, [((t
      BuArO)3tacn)U] (1) reacts with CO2 in a 2e- reduction to produce CO and a
      dinuclear U(IV/IV) mu-oxygen bridged complex [{((t-BuArO)3tacn)U}2(mu-O)] (2).
      This reaction proceeds via a dinuclear CO2-bridged intermediate 3. Also,
      mononuclear 1 was treated with 1 atm of CO to yield dinuclear [{((t
      BuArO)3tacn)U}2(mu-CO)] (4) with a CO ligand bridging two uranium ions in an
      unprecedented mu:eta1,eta1 fashion. The mixed-valent azido-bridged U(III/IV)
      complex 5 was synthesized from trivalent 1 and tetravalent [((t
      BuArO)3tacn)U(N3)] and serves as an isostructural analogue of triatomic-bridged
      intermediate 3 as well as an electronic model for mixed-valent 4.

PMID- 16089444
TI  - Kinetic resolutions of azomethine imines via copper-catalyzed [3 + 2]
      cycloadditions.
AB  - An effective method has been developed for the kinetic resolution of racemic
      azomethine imines via [3 + 2] cycloadditions with alkynes catalyzed by a chiral
      copper complex. Efficient kinetic resolution is observed for a variety of N1 and
      C5 substituents on the dipole, thereby furnishing a wide array of useful
      enantioenriched azomethine imines, which can readily be transformed into
      monocyclic and bicyclic pyrazolidinones.

PMID- 16089445
TI  - Sterically congested in-methylcyclophanes.
AB  - The crowded in-methylcyclophane 9 was prepared by condensation of 1,8,13
      tris(bromomethyl)-9-methyltriptycene and 1,3,5-tris(mercaptomethyl)benzene under
      high dilution conditions. Oxidation of 9 gave the highly crystalline trisulfone
      10, and its X-ray structure was determined. The in-methyl carbon atoms of the two
      independent molecules in the structure are only 2.90 and 2.87 A from the centroid
      of the basal aromatic ring, the closest such contacts ever observed. In addition,
      the C-CH3 bonds in these cyclophanes are compressed; the two independent bond
      distances are 1.475 and 1.495 A, significantly shorter than the ca. 1.54 A
      distances found in similar but uncongested molecules.

PMID- 16089446
TI  - A terminal Ni(III)-imide with diverse reactivity pathways.
AB  - The synthesis and structure of the beta-diketiminato Ni(I) lutidine adducts
      [MexNN]Ni(2,4-lutidine) (x = 2 (2); x = 3 (3)) are described which serve as
      synthons to the "naked" 13-electron [MexNN]Ni fragments in reactions with N3Ad to
      give Ni-imido complexes. The singly bridged imide {[Me2NN]Ni}2(mu-NAd) (4)
      possesses short Ni-Ni (2.506(1) A) and Ni-N(imido) distances (1.732(4)-1.752(4)
      A). Steric modification of the beta-diketiminate ligand to include an additional
      methyl group in the N-aryl 4-position affords the Ni(III) terminal imide
      [Me3NN]Ni=NAd (8) isolated in 52% yield. The X-ray structure of terminal imide 8
      reveals a contracted Ni-N(imido) bond distance (1.662(2) A) and an only somewhat
      bent imido linkage (Ni-N-C = 164.5(2) degrees ) consistent with a significant
      degree of multiple bond character. Frozen glass EPR studies of 5 indicate a
      rhombic environment in which one of the signals exhibits strong hyperfine
      coupling (A = 22 G) to the imido 14N (I = 1) nucleus. The terminal imide 5
      undergoes complete imido group transfer to CO and CNBut to give AdNCO and
      AdNCNBut, respectively, as well as with PMe3 to afford AdN=PMe3. Exemplifying the
      radical character at the imido N atom, 5 adds to cobaltocene and abstracts a H
      atom from 1,4-cyclohexadiene to give the Ni(II)-amides [Me3NN]Ni-NAd(eta4
      C5H5)CoCp (7) and [Me3NN]Ni-NHAd (8).

PMID- 16089447
TI  - Copper(II) acetate promoted intramolecular diamination of unactivated olefins.
AB  - A concise method for the synthesis of cyclic sulfamides and vicinal diamines is
      presented. This method is enabled by Cu(OAc)2 and demonstrates a new
      transformation for this metal. Both five- and six-membered vicinal diamine
      containing heterocycles have been synthesized in good to excellent yields, and
      substrate-based asymmetric induction has been achieved. This is the first
      reported example of intramolecular diamination of olefins.

PMID- 16089448
TI  - Catalytic enantioselective desymmetrization of meso-N-acylaziridines with TMSCN.
AB  - A catalytic enantioselective desymmetrization of meso-N-p-nitrobenzoylaziridines
      with TMSCN was developed using a chiral gadolinium catalyst generated from
      Gd(OiPr)3 and d-glucose-derived ligand 1. In this reaction, the addition of a
      catalytic amount of trifluoroacetic acid (TFA) improved enantioselectivity. High
      enantioselectivity was obtained from a range of meso-aziridines at 0-60 degrees
      C. The product could be easily transformed into beta-amino acids. Thus, the
      developed catalytic enantioselective desymmetrization reaction allowed for
      efficient catalytic synthesis of chiral cyclic beta-amino acids. The
      incorporation of TFA into the catalyst complex was observed using ESI-MS.
      Generation of this new complex might be the origin of the improved
      enantioselectivity.

PMID- 16089449
TI  - Synthesis and complete stereochemical assignment of psymberin/irciniastatin A.
AB  - We describe a concise and flexible synthetic avenue for the preparation of
      compounds with structures relevant to those proposed for the novel marine-derived
      differential cytotoxins psymberin and irciniastatin A. Our efforts led to their
      complete stereochemical assignment and the notion that psymberin and
      irciniastatin A are identical compounds. Our total synthesis features an
      interesting termini-differentiating lactolization of a dialdehyde obtained from a
      C2-symmetrical bis-olefin precursor, a mild platinum-catalyzed hydrolysis of an
      epimerizable nitrile, a novel protocol to prepare sensitive methyl imidates, and
      a one-pot conversion of these imidates to N-acyl aminals. Starting from fragments
      5-7 (prepared in 7-8 steps each, 30-49% overall yield) the synthesis of
      psymberin/irciniastatin A was completed in an additional 9 steps and 30% yield
      (17 steps longest linear sequence, 8.9% overall).

PMID- 16089450
TI  - Asymmetric Mannich reactions of beta-keto esters with acyl imines catalyzed by
      cinchona alkaloids.
AB  - Cinchona alkaloids catalyze the enantioselective Mannich reaction of beta-keto
      esters with acyl aryl imines. The reaction requires 10 mol % of cinchonine or
      cinchonidine. The reaction products are obtained in good yields (81-99%), high
      enantioselectivities (80-96% ee), and in diastereoselectivities that range from
      1:1 to >95:5. The cinchonine-catalyzed reaction provides access to highly
      functionalized building blocks used in the asymmetric synthesis of a
      dihydropyrimidone and beta-amino alcohol.

PMID- 16089451
TI  - Synthesis of substituted oxa- and aza[3.2.1] and [4.3.1]bicyclics via an
      unprecedented molybdenum-mediated 1,5-"Michael-type" reaction.
AB  - The direct internal nucleophilic functionalization of a pi-bound carbon of
      neutral TpMo(CO)2(5-oxo-eta3-pyranyl) and TpMo(CO)2(5-oxo-eta3-pyridinyl)
      complexes by enolates represents a new reaction profile for neutral
      TpMo(CO)2(eta3-allyl) complexes. This Mo-mediated "1,5-Michael reaction" proceeds
      in good to excellent yields and provides, after demetalation, a new and efficient
      synthetic approach to oxa- and aza[3.2.1]bicyclics of high enantiomeric purity.

PMID- 16089452
TI  - Gold(I)-catalyzed intramolecular acetylenic Schmidt reaction.
AB  - Substituted pyrroles were prepared by a gold(I)-catalyzed acetylenic Schmidt
      reaction of homopropargyl azides. The reaction allows for regiospecific
      substitution at each position of the pyrrole ring under mild conditions. A
      mechanism in which azides serve as nucleophiles toward gold(I)-activated alkynes
      with subsequent gold(I)-aided expulsion of dinitrogen is proposed.

PMID- 16089453
TI  - Surface-enhanced Raman scattering and polarized photoluminescence from
      catalytically grown CdSe nanobelts and sheets.
AB  - We have successfully fabricated single-crystalline CdSe nanowires, nanobelts, and
      sheets by a chemical vapor deposition (CVD) method assisted with laser ablation.
      The synthesized CdSe nanostructures have hexagonal wurtzite phase as
      characterized by X-ray diffraction (XRD). CdSe nanobelts can range in length from
      several tens to a hundred micrometers, in thickness from 40 to 70 nm, and a
      tapered width which is approximately 3 microm at one end and tapers off to
      approximately 100 nm at a catalytic gold particle. Both selected area electron
      diffraction (SAED) and high-resolution transmission electron microscopic (HRTEM)
      measurements show that the single-crystalline hexagonal belts and sheets grew
      along the [0.1-1.0] direction with side surface of +/-(0 0 0 1) and top surface
      of +/-(2 -1 -1 0). While the growth mechanism of nanobelts complies with a
      combination of vapor-liquid-solid (VLS) and vapor-solid (VS) processes, the
      formation of sheets is primarily based on the VS mechanism. For comparison, the
      phonon modes of CdSe nanobelts and bulk powder have been measured by surface
      enhanced Raman scattering (SERS) and normal Raman scattering (NRS) spectroscopies
      with off- and near-resonant excitations. A blue-shift of 2.4 cm(-1) for the
      longitudinal optical (LO) phonon of CdSe nanobelts, relative to bulk CdSe, is
      attributed to a lattice contraction in the belt structure, which is confirmed by
      the XRD measurement. Room-temperature microphotoluminescence (PL) at
      approximately 1.74 eV from single CdSe nanobelts shows a 3-fold enhancement
      compared to that from bulk CdSe powder and displays a partial polarization
      dependence of emission angles.

PMID- 16089454
TI  - Hydrogen-mediated reductive coupling of conjugated alkynes with ethyl (N
      Sulfinyl)iminoacetates: synthesis of unnatural alpha-amino acids via rhodium
      catalyzed C-C bond forming hydrogenation.
AB  - Rhodium-catalyzed hydrogenation of 1,3-enynes 1a-8a and 1,3-diynes 9a-13a at
      ambient temperature and pressure in the presence of ethyl (N-tert
      butanesulfinyl)iminoacetate and ethyl (N-2,4,6
      triisopropylbenzenesulfinyl)iminoacetates, respectively, results in reductive
      coupling to afford unsaturated alpha-amino acid esters 1b-13b in good to
      excellent yields with exceptional levels of regio- and stereocontrol. Further
      hydrogenation of the diene containing alpha-amino acid esters 1b-8b using
      Wilkinson's catalyst at ambient temperature and pressure results in
      regioselective reduction to afford the beta,gamma-unsaturated alpha-amino acid
      esters 1c-8c in good to excellent yields. Exhaustive hydrogenation of the
      unsaturated side chains of the Boc- and Fmoc-protected derivatives of enyne and
      diyne coupling products 14b-16b occurs in excellent yield using Crabtree's
      catalyst at ambient temperature and pressure providing the alpha-amino acid
      esters 14d-16d, which possess saturated side chains. Finally, cross-metathesis of
      the Boc-protected reductive coupling product 14b with cis-1,4-diacetoxy-2-butene
      proceeds readily to afford the allylic acetate 14e. Isotopic labeling studies
      that involve reductive coupling of enyne 1a and diyne 9a under an atmosphere of
      elemental deuterium corroborate a catalytic mechanism in which oxidative coupling
      of the alkyne and imine residues is followed by hydrogenolytic cleavage of the
      resulting metallacycle. A stereochemical model accounting for the observed sense
      of asymmetric induction is provided. These studies represent the first use of
      imines as electrophilic partners in hydrogen-mediated reductive carbon-carbon
      bond formation.

PMID- 16089455
TI  - Endohedral chemistry of C60-based fullerene cages.
AB  - Fullerenes have unique chemistry owing to their cage structure, their richness in
      pi-electrons, and their large polarizabilities. They can trap atoms and small
      molecules to generate endohedral complexes as superconductors, drug carriers,
      molecular reactors, and ferroelectric materials. An important goal is to develop
      effective methods that can affect the behavior of the atoms and small molecules
      trapped inside the cage. In this paper, the quantum chemical density functional
      theory was employed to demonstrate that the stability and position of a guest
      molecule inside the C60 cage can be changed, and its orientation controlled, by
      modifying the C60 cage shell. The outside attachment of two hydrogen atoms to two
      adjacent carbon atoms located between two six-membered rings of the C60 cage
      affects the orientation of the LiF molecule inside and increases the stability of
      LiF inside the cage by 45%. In contrast, when 60 hydrogen atoms were attached to
      the outside surface of the C60 cage, thus transforming all C=C double bonds into
      single bonds, the stability of the LiF inside was reduced by 34%. If two adjacent
      carbon atoms were removed from C60, the stability of LiF inside this defect C60
      was reduced by 41%.

PMID- 16089456
TI  - Spontaneous "phase separation" of patterned binary alkanethiol mixtures.
AB  - This article describes novel phase-separation behavior by a binary mixture of
      alkanethiols when deposited onto a gold surface using micro- and nanodeposition
      tools, such as microcontact printing (muCP) and dip-pen nanolithography (DPN).
      This behavior is significantly different than that observed in the bulk. We
      demonstrate this behavior using three model compounds: 16-mercaptohexadecanoic
      acid (MHA), 1-octadecanethiol (ODT), and CF3(CF2)11(CH2)2SH (PFT). The identity
      of the resulting segregated structure is confirmed by lateral force microscopy
      (LFM) and by selective metal-organic coordination chemistry. Importantly, this
      phenomenon can be exploited to print sub-100 nm wide alkanethiol lines via
      conventional muCP and to form sub-15 nm features using DPN, which is below the
      ultimate resolution of both these techniques. We also demonstrate that these nano
      patterned materials can serve as templates for constructing more complex
      architectures.

PMID- 16089457
TI  - Structure of zone-cast HBC-C12H25 films.
AB  - The structure of a thin zone-cast film of the hexa-n-dodecyl-substituted hexa
      peri-benzocoronene (HBC) has been investigated using grazing incidence X-ray
      diffraction. A model with an orthorhombic unit cell containing two molecules
      accounts well for the observations. The molecules are arranged in a "herringbone"
      structure resembling the packing observed for unsubstituted HBC. The molecular
      disk planes are oriented perpendicularly to the substrate, rotated by
      approximately 39 degrees about the film normal. The relatively long side chains
      of dodecyl were found to be in an ordered interdigitated state. The aliphatic
      side chains and the aromatic HBC-cores segregate to form regular vertical domains
      spanning the film thickness. For in-plane rocking scans a discrete orientation
      distribution is observed with peaks at regular angle intervals. We interpret this
      as a grain boundary effect induced by alkyl chain stacking faults.

PMID- 16089458
TI  - Theoretical studies of stereoselectivities of intramolecular aldol cyclizations
      catalyzed by amino acids.
AB  - The effects of different amino acid catalysts and substrate substituents on the
      stereoselectivity of the title reactions have been studied with the aid of
      density functional theory methods. Experimental data available in the literature
      have been compiled. B3LYP/6-31G(d) calculations match the general experimental
      trends and provide useful insights into the origins of the variations in
      stereoselectivities. Acyclic primary amino acids allow a greater conformational
      flexibility in the aldol transition states compared with proline. This makes them
      poorer enantioselective catalysts with triketone substrates with a methyl ketone
      side chain. The steric repulsion upon substitution at the terminal methyl group
      increases the energy difference between anti- and syn-chairs with primary amino
      acid catalysts and, consequently, the stereoselectivities. Proline, in contrast,
      is a poor catalyst for the latter reactions because the substituent's steric
      bulkiness raises the activation energy of the favored C-C bond-forming pathway.

PMID- 16089459
TI  - Generalized Mulliken-Hush analysis of electronic coupling interactions in
      compressed pi-stacked porphyrin-bridge-quinone systems.
AB  - Donor-acceptor interactions were investigated in a series of unusually rigid,
      cofacially compressed pi-stacked porphyrin-bridge-quinone systems. The two-state
      generalized Mulliken-Hush (GMH) approach was used to compute the coupling matrix
      elements. The theoretical coupling values evaluated with the GMH method were
      obtained from configuration interaction calculations using the INDO/S method. The
      results of this analysis are consistent with the comparatively soft distance
      dependences observed for both the charge separation and charge recombination
      reactions. Theoretical studies of model structures indicate that the phenyl units
      dominate the mediation of the donor-acceptor coupling and that the relatively
      weak exponential decay of rate with distance arises from the compression of this
      pi-electron stack.

PMID- 16089460
TI  - Quantum tunneling and quantum phase interference in a [Mn(II)2Mn(III)2] single
      molecule magnet.
AB  - [Mn4(hmp)6(H2O)2(NO3)2](NO3)2.2.5H2O (1) has been synthesized from the reaction
      of 2-hydroxymethylpyridine (Hhmp) with Mn(NO3)2.4H2O in the presence of
      tetraethylammonium hydroxide. 1 crystallizes in the triclinic P space group with
      two crystallographically independent centrosymmetrical [Mn4(hmp)6(H2O)2(NO3)2]2+
      complexes in the packing structure. Four Mn ions are arranged in a double
      cuboidal fashion where outer Mn2+ are heptacoordinated and inner Mn3+ are
      hexacoordinated. dc magnetic measurements show that both Mn2+...Mn3+ and
      Mn3+...Mn3+ interactions are ferromagnetic with J(wb)/k(B) = +0.80(5) K, and
      J(bb)/k(B) = +7.1(1) K, respectively, leading to an S(T) = 9 ground state.
      Combined ac and dc measurements reveal the single-molecule magnet (SMM) behavior
      of 1 with both thermally activated and ground-state tunneling regimes, including
      quantum phase interference. In the thermally activated regime, the characteristic
      relaxation time (tau) of the system follows an Arrhenius law with tau0 = 6.7 x
      10(-)(9) s and delta(eff)/k(B) = 20.9 K. Below 0.34 K, tau saturates indicating
      that the quantum tunneling of the magnetization becomes the dominant relaxation
      process as expected for SMMs. Down to 0.04 K, field dependence of the
      magnetization measured using the mu-SQUID technique shows the presence of very
      weak inter-SMM interactions (zJ'/k(B) approximately -1.5 x 10(-3) K) and allows
      an estimation of D/k(B) at -0.35 K. Quantum phase interference has been used to
      confirm the D value and to estimate the transverse anisotropic parameter to
      E/k(B) = +0.083 K and the ground-state tunnel splitting delta(LZ) = 3 x 10(-7) K
      at H(trans) = 0 Oe. These results rationalize the observed tunneling time
      (tau(QTM)) and the effective energy barrier (delta(eff)).

PMID- 16089461
TI  - Doping of polyaniline by acid-base chemistry: density functional calculations
      with periodic boundary conditions.
AB  - Calculations with Gaussian orbitals and periodic boundary conditions using
      several density functionals are carried out to study the proton-doping of
      polyaniline. We explore previously proposed mechanisms to explain the spectacular
      increase of the electrical conductivity of polyaniline upon protonation. The
      structural and spectroscopic theoretical predictions for both polaron and
      bipolaron lattices agree quite well with the experimental data, and we find that
      the bipolaron structure is lower in energy.

PMID- 16089462
TI  - Quantum dot-conjugated hybridization probes for preliminary screening of siRNA
      sequences.
AB  - In the present study, we describe the design and fabrication of quantum dot
      conjugated hybridization probes and their application to the development of a
      comparatively simple and rapid procedure for the selection of highly effective
      small-interfering RNA (siRNA) sequences for RNA interference (RNAi) in mammalian
      cells, for example, siRNAs with high accessibility and affinity to the respective
      mRNA target. A single-stranded siRNA was conjugated with a quantum dot and used
      as a hybridization probe. The target mRNA was amplified in the presence of Cy5
      labeled nucleotides, and Cy5-mRNA served as a hybridization sample. The formation
      of siRNA/mRNA duplexes during a comparatively short hybridization time (1 h) was
      used as a criterion for the selection of highly effective, target-specific siRNA
      sequences. The accessibility and affinity of the siRNA sequence for the target
      mRNA site were determined by fluorescence resonance energy transfer (FRET)
      between a quantum dot (donor) and a fluorescent dye molecule (Cy5, acceptor)
      localized at an appropriate distance from each other when hybridization occurred.
      The FRET signal was observed only when there was high accessibility between an
      antisense siRNA and a sense mRNA and did not appear in the case of mismatch
      siRNAs. Moreover, the amplitude of the FRET signal significantly correlated with
      the specific effect of siRNA on the expression of the target mRNA and protein,
      determined in native cells by RT-PCR and immunoblot analysis, respectively.

PMID- 16089463
TI  - Differential effects of the Zn-His-Bkb vs Zn-His-[Asp/Glu] triad on Zn-core
      stability and reactivity.
AB  - The most common partner of the Zn-bound His is the Asp/Glu carboxylate side chain
      in catalytic Zn sites and the backbone (Bkb) carbonyl group in structural Zn
      sites. To elucidate the factors governing the selection of the second-shell
      partner of the Zn-bound His in structural/catalytic Zn sites, systematic studies
      using density functional theory and continuum dielectric calculations were
      performed to determine the relative contributions of the second-shell Bkb
      carbonyl and the Asp/Glu carboxylate to the Zn-core stability and reactivity. The
      results show that the contributions of the second-shell Bkb carbonyl and Asp/Glu
      carboxylate to the Zn-core stability depend mainly on the solvent accessibility
      of the Zn-site and the composition of the Zn-core. They reveal the advantage of a
      second-shell Bkb carbonyl in anionic Zn cavities: it stabilizes anionic, buried
      Zn-cores more than the corresponding negatively charged Asp/Glu carboxylate, thus
      explaining the absence of the Zn-His-Asp/Glu triad in structural [Zn(Cys)3(His)]-
      cores. They also reveal the advantage of a second-shell Asp/Glu carboxylate in
      catalytic Zn-cores: relative to a Bkb carbonyl group, it increases (i) the HOMO
      energy of the cationic/neutral zinc core, (ii) the reactivity of the attacking Zn
      bound OH-, (iii) electron transfer to the substrate, and (iv) the stability of
      the metal complex upon electron transfer. Furthermore, a second-shell Asp/Glu
      carboxylate could facilitate product release in the common cationic catalytic
      cores, by acting as a proton acceptor of the Zn-bound His creating an Asp...His-
      dyad that stabilizes the zinc dication more than the respective Bkb...His0 dyad.

PMID- 16089464
TI  - Boolean control of aptamer binding states.
AB  - Molecules that perform Boolean calculations can analyze a series of inputs and
      make a decision to produce or not to produce an output, based on the presence or
      absence of inputs and a particular formula they encode. We now report that
      molecular computation performed by deoxyribozyme-based logic gates can be used to
      control the functional state of aptamers, switching them on or off based on the
      outcome of such computation.

PMID- 16089465
TI  - Dendrimers made of porphyrin cores and carbazole chromophores as peripheral
      units. Absorption spectra, luminescence properties, and oxidation behavior.
AB  - Luminescent and redox-active porphyrin-based dendrimers of first and second
      generation have been synthesized, and their absorption spectra, photophysical
      properties, and oxidation behavior have been investigated, together with those of
      the corresponding aldehyde carbazole precursors. All the dendrimers contain a
      porphyrin core and carbazole-based chromophores as branches. The structural
      formulas of the new species are represented in Figures 1 and 2, with the
      corresponding schematizations. The absorption spectra of the aldehyde carbazole
      precursors A1-A6 in dichloromethane exhibit intense transitions in the UV region,
      centered on the carbazole and benzaldehyde subunits. The lowest-energy absorption
      bands receive contribution from charge-transfer transitions. Compounds A1-A6 are
      luminescent at room temperature in fluid solution; such a luminescence is
      attributed to twisted intramolecular charge-transfer excited states. The
      luminescence at 77 K in a rigid matrix is blue-shifted with respect to room
      temperature emission and is assigned to locally excited states. Absorption
      spectra of the porphyrin-cored dendrimers P1-P6 appear additive as they are
      constituted by visible bands due to porphyrin absorption and bands in the UV
      region due to transitions centered on the carbazole-based branches. Emission
      spectra of P1-P6 both at 77 K and at room temperature are typical of porphyrin
      species and independent of excitation wavelength, indicating that the light
      collected by the peripheral chromophores is quantitatively transferred to the
      core. All the compounds exhibit a rich oxidation behavior in 1,2-dichloroethane
      solution, with reversible processes centered on the different carbazole subunits.
      Interaction between the different carbazole centers depends on the size of the
      spacer interposed.

PMID- 16089466
TI  - Folate-receptor-mediated delivery of InP quantum dots for bioimaging using
      confocal and two-photon microscopy.
AB  - A novel method for the synthesis of highly monodispersed hydrophillic InP-ZnS
      nanocrystals and their use as luminescence probes for live cell imaging is
      reported. Hydrophobic InP-ZnS nanocrystals are prepared by a new method that
      yields high-quality, luminescent core-shell nanocrystals within 6-8 h of total
      reaction time. Then by carefully manipulating the surface of these passivated
      nanocrystals, aqueous dispersions of folate-conjugated nanocrystals (folate-QDs)
      with high photostability are prepared. By use of confocal microscopy, we
      demonstrate the receptor-mediated delivery of folic acid conjugated quantum dots
      into folate-receptor-positive cell lines such as KB cells. These folate-QDs tend
      to accumulate in multi-vescicular bodies of KB cells after 6 h of incubation.
      Receptor-mediated delivery was confirmed by comparison with the uptake of these
      particles in folate-receptor-negative cell lines such as A549. Efficient two
      photon excitation of these particles and two-photon imaging using these particles
      are also demonstrated. The use of these InP-ZnS nanoparticles and their efficient
      two-photon excitation can be potentially useful for deep tissue imaging for
      future in vivo studies.

PMID- 16089467
TI  - Synthesis, structure, and reactivity of O-donor Ir(III) complexes: C-H activation
      studies with benzene.
AB  - Various new thermally air- and water-stable alkyl and aryl analogues of (acac
      O,O)2Ir(R)(L), R-Ir-L (acac-O,O = kappa2-O,O-acetylacetonate, -Ir- is the trans
      (acac-O,O)2Ir(III) motif, R = CH3, C2H5, Ph, PhCH2CH2, L = Py) have been
      synthesized using the dinuclear complex [Ir(mu-acac-O,O,C3)-(acac-O,O)(acac
      C3)]2, [acac-C-Ir]2, or acac-C-Ir-H2O. The dinuclear Ir (III) complexes, [Ir(mu
      acac-O,O,C3)-(acac-O,O)(R)]2 (R = alkyl), show fluxional behavior with a five
      coordinate, 16 electron complex by a dissociative pathway. The pyridine adducts,
      R-Ir-Py, undergo degenerate Py exchange via a dissociative mechanism with
      activation parameters for Ph-Ir-Py (deltaH++ = 22.8 +/- 0.5 kcal/mol; deltaS++ =
      8.4 +/- 1.6 eu; deltaG++298 K) = 20.3 +/- 1.0 kcal/mol) and CH3-Ir-Py (deltaH++ =
      19.9 +/- 1.4 kcal/mol; deltaS++ = 4.4 +/- 5.5 eu; deltaG++298 K) = 18.6 +/- 0.5
      kcal/mol). The trans complex, Ph-Ir-Py, undergoes quantitatively trans-cis
      isomerization to generate cis-Ph-Ir-Py on heating. All the R-Ir-Py complexes
      undergo quantitative, intermolecular CH activation reactions with benzene to
      generate Ph-Ir-Py and RH. The activation parameters (deltaS++ =11.5 +/- 3.0 eu;
      deltaH++ = 41.1 +/- 1.1 kcal/mol; deltaG++298 K = 37.7 +/- 1.0 kcal/mol) for CH
      activation were obtained using CH3-Ir-Py as starting material at a constant ratio
      of [Py]/[C6D6] = 0.045. Overall the CH activation reaction with R-Ir-Py has been
      shown to proceed via four key steps: (A) pre-equilibrium loss of pyridine that
      generates a trans-five-coordinate, square pyramidal intermediate; (B)
      unimolecular, isomerization of the trans-five-coordinate to generate a cis-five
      coordinate intermediate, cis-R-Ir- square; (C) rate-determining coordination of
      this species to benzene to generate a discrete benzene complex, cis-R-Ir-PhH; and
      (D) rapid C-H cleavage. Kinetic isotope effects on the CH activation with
      mixtures of C6H6/C6D6 (KIE = 1) and with 1,3,5-C6H3D3 (KIE approximately 3.2 at
      110 degrees C) are consistent with this reaction mechanism.

PMID- 16089468
TI  - Single polymer chains as specific transducers of molecular recognition in
      scanning probe microscopy.
AB  - A new approach for the specific detection and mapping of single molecule
      recognition is presented, based on the nonlinear elastic behavior of a single
      polymer chain. The process of molecular recognition between a ligand and a
      receptor is inherently accompanied by a decrease in the translational and
      rotational degrees of freedom of the two molecules. We show that a polymeric
      tether linked to the ligand can effectively transduce the configurational
      constraint imposed by molecular recognition into a measurable force, which is
      dominated by the entropic elasticity of the polymer. This force is specifically
      characterized by a strong nonlinearity when the extension of the polymer
      approaches its contour length. Thus, a polymer chain tethering the ligand to an
      oscillating cantilevered tip gives rise to a highly anharmonic motion upon ligand
      receptor binding. Higher-harmonics atomic force microscopy allows us to detect
      this phenomenon in real time as a specific signature for the probing and mapping
      of single-molecule recognition.

PMID- 16089469
TI  - Where is the spin? Understanding electronic structure and g-tensors for ruthenium
      complexes with redox-active quinonoid ligands.
AB  - Understanding the bonding in transition metal complexes with redox-active ligands
      is a major challenge, for example in redox catalysis or in bioinorganic
      chemistry. In this work, electronic g-tensors, spin-density distributions, and
      electronic structure have been studied by different density functional methods
      for an extended series of complexes [Ru(acac)2(L)]n (n = -1, 0, +1; L = redox
      active o-quinonoid ligand). Comparison is made with experimental g-tensors and g
      tensor-based oxidation-state assignments for a number of experimentally studied
      examples, using both gradient-corrected (BP86) and hybrid functionals (B3LYP,
      BHLYP) representing a range of exact-exchange admixtures. Reasonable, albeit not
      perfect, agreement with experimental g-tensors is obtained in one-component DFT
      calculations with hybrid functionals. Analyses of spin densities confirm the
      assignment of the cationic complexes as predominantly d5-Ru(III) with a neutral
      quinonoid ligand. However, this conclusion is obtained only after inclusion of
      the appreciable spin polarization of the unrestricted determinant, while the
      singly occupied molecular orbital (SOMO) is localized more on the acac ligands.
      The anionic complexes turn out to be approximately halfway between a d6
      Ru(II)/semiquinone and a d5-Ru(III)/catecholate formulation, but again only after
      taking into account the extensive spin polarization. Even the previous assignment
      of the neutral parent systems as d5-Ru(III)/semiquinone is not accurate, as a d6
      Ru(II)/quinone resonance structure contributes to some extent. Very unusual
      trends in the spin contamination of the Kohn-Sham determinant with increasing
      exact-exchange admixture in some of the cationic complexes have been traced to an
      interplay between spin delocalization and spin polarization.

PMID- 16089470
TI  - Hydrogen bonding and cooperativity in isolated and hydrated sugars: mannose,
      galactose, glucose, and lactose.
AB  - The conformation of phenyl-substituted monosaccharides (mannose, galactose, and
      glucose) and their singly hydrated complexes has been investigated in the gas
      phase by means of a combination of mass selected, conformer specific ultraviolet
      and infrared double resonance hole burning spectroscopy experiments, and ab
      initio quantum chemistry calculations. In each case, the water molecule inserts
      into the carbohydrate at a position where it can replace a weak intramolecular
      interaction by two stronger intermolecular hydrogen bonds. The insertion can
      produce significant changes in the conformational preferences of the
      carbohydrates, and there is a clear preference for structures where cooperative
      effects enhance the stability of the monosaccharide conformers to which the water
      molecule chooses to bind. The conclusions drawn from the study of monosaccharide
      water complexes are extended to the disaccharide lactose and discussed in the
      light of the underlying mechanisms that may be involved in the binding of
      carbohydrate assemblies to proteins and the involvement, or not, of key
      structural water molecules.

PMID- 16089471
TI  - Chromium(III) octaethylporphyrinato tetracarbonylcobaltate: a highly active,
      selective, and versatile catalyst for epoxide carbonylation.
AB  - The development of a highly active and selective porphyrin-based epoxide
      carbonylation catalyst, [(OEP)Cr(THF)2][Co(CO)4] (1; OEP = octaethylporphyrinato;
      THF = tetrahydrofuran), is detailed. Complex 1 is a separated ion pair composed
      of a tetracarbonylcobaltate anion and an octahedral chromium porphyrin complex
      axially ligated by two THF ligands. Regarding the carbonylation of epoxides to
      beta-lactones, catalyst 1 exhibits excellent turnover numbers (up to 10,000) and
      turnover frequencies (up to 1670 h(-1)), with regioselective carbonyl insertion
      occurring between the oxygen and the sterically less hindered carbon of the
      epoxide substrate. Complex 1 is highly tolerant of nonprotic functional groups,
      carbonylating an array of aliphatic and cycloaliphatic epoxides, as well as
      epoxides with pendant ethers, esters, and amides. With careful control of
      reaction conditions in the carbonylation of glycidyl esters, the exclusive
      production of either the beta- or gamma-lactone isomer was achieved. Through
      analysis of reaction stereochemistry, a mechanism for the formation of gamma
      lactone products was proposed. Overall, a broad array of synthetically useful
      lactones has been synthesized in a rapid and selective fashion by catalytic
      carbonylation using [(OEP)Cr(THF)2][Co(CO)4].

PMID- 16089472
TI  - Monomolecular DNA nanoparticles for intravenous delivery of genes.
AB  - Delivery is the major obstacle to success of nucleic-acid-based therapies. We
      have neutralized DNA with a cationic detergent (C12CCP) obtained by amide bond
      formation between dodecanoic acid, cysteinyl-cysteine, and diaminopropane.
      Subsequent detergent polymerization by formation of intermolecular disulfide
      bonds within the condensed plasmid DNA leads to 32-nm-large neutral particles.
      (C12CCP)n/DNA complexes are more stable than those formed with other gene
      delivery agents toward exchange with extracellular polyanions such as
      glycosaminoglycans. Yet exposure to phosphatidylserine, an ubiquitous
      intracellular anionic lipid, still releases DNA from the complexes for
      transcription of the carried gene. Pharmacokinetics and biodistribution in mice
      showed that 25% of the complexes were still circulating after 30 min (2% for
      other cationic lipid vectors) in a form essentially not bound to blood cells.
      Altogether, straightforward control over size and surface charge, stability
      toward aggregation or exchange, and favorable pharmacokinetics make these
      complexes attractive vehicles for reaching tumor metastases after injection in
      the blood circulation.

PMID- 16089473
TI  - Fine tuning the anion binding properties of 2,6-diamidopyridine dipyrromethane
      hybrid macrocycles.
AB  - The synthesis, characterization, and anion-binding properties of a series of 2,6
      diamidopyridine dipyrromethane hybrid macrocycles is presented. As part of this
      work, a new method for effecting the oxidation of dipyrromethane-based
      macrocycles in organic solvents has been developed. The macrocyclic frameworks
      presented here stand out because of their ease of synthesis and tunable anion
      binding properties. Evidence for anion binding was obtained from UV-vis
      spectroscopic titrations carried out in acetonitrile. The results clearly
      indicate that by changing the flexibility, cavity size, and directionality of
      anion-binding moieties in the macrocyclic framework the anion selectivity may be
      changed dramatically. These results are in accord with density functional theory
      molecular modeling calculations performed on one member of the series.

PMID- 16089474
TI  - Kinetics of the interconversion of parahydrogen and orthohydrogen catalyzed by
      paramagnetic complex ions.
AB  - The rate constants of para-/orthohydrogen (p-/o-H2) nuclear spin isomerization
      have been measured by means of 1H NMR in deuterated solvents at 298.2 K. The
      indicated reaction is catalyzed by paramagnetic complex ions giving rate
      constants that are proportional to the concentrations of the catalysts. The
      second-order rate constants are directly proportional to the squares of the
      magnetic moments for the solvated metal complexes for two classifications:
      M(solv)m2+, M = 3d transition metals; Ln(solv)n3+, where in 1:9 D2O-CD3CN the
      aqua complexes are the predominant species, Ln = lanthanides. The other 3d
      transition metal complexes with different ligands show rate constants that also
      depend on the sizes of ligands. Whereas the correlation between the second-order
      rate constants and magnetic moments is consistent with Wigner's theory, the size
      of catalyst shows a more modest effect on the rate constants than expected. The
      effective collision radii of the complexes, calculated from the rate constants,
      proved to be approximately constant for each series of solvated metal complexes.

PMID- 16089475
TI  - Water production reaction on Rh110.
AB  - By means of scanning tunneling microscopy and density functional theory
      calculations, we studied the water formation reaction on the Rh(110) surface when
      exposing the (2 x 1)p2mg-O structure to molecular hydrogen, characterizing each
      of the structures that form on the surface during the reaction. First the
      reaction propagates on the surface as a wave front, removing half of the initial
      oxygen atoms. The remaining 0.5 monolayers of O atoms rearrange in pairs, forming
      a c(2 x 4) structure. Second, as the reaction proceeds, areas of an intermediate
      structure with c(2 x 2) symmetry appear and grow at the expense of the c(2 x 4)
      phase, involving all the oxygen atoms present on the surface. Afterward, the c(2
      x 2) islands shrink, indicating that complete hydrogenation occurs at their
      edges, leaving behind a clean rhodium substrate. Two possible models for the c(2
      x 2) structure, where not only the arrangement but also the chemical identity is
      different, are given. The first one is a mixed H + O structure, while the second
      one resembles the half-dissociated water layer already proposed on other metal
      surfaces. In both models, the high local oxygen coverage is achieved by the
      formation of a hexagonal network of hydrogen bonds.

PMID- 16089476
TI  - Electronically selective chemical functionalization of carbon nanotubes:
      correlation between Raman spectral and electrical responses.
AB  - Single-walled carbon nanotubes (SWNTs) demonstrate remarkable electronic and
      mechanical properties useful in developing areas such as nanoelectromechanical
      systems and flexible electronics. However, the highly inhomogeneous electronic
      distribution arising from different diameters and chirality in any given as
      synthesized SWNT samples imposes severe limitations. Recently demonstrated
      selective chemical functionalization methods may provide a simple scalable means
      of eliminating metallic tubes from SWNT transistors and electronic devices. Here,
      we report on combined electron transport and Raman studies on the reaction of 4
      bromobenzene diazonium tetrafluoroborate directly with single and networks of
      SWNT transistors. First, Raman studies are carried out on isolated individual
      SWNTs grown on SiO2/Si substrates by chemical vapor deposition with and without
      metal contacts. Metallic tubes are found to have, on average, higher reactivity
      toward diazonium reagents. However, a considerable degradation of electrical
      properties of semiconducting tubes occurs if the reaction is carried out to the
      point where the conductivity of metallic tubes is significantly suppressed.
      Insights from single-tube studies are then applied to elucidate the electrical
      and the Raman responses of SWNT random network transistors of different channel
      lengths to chemical functionalization.

PMID- 16089477
TI  - A quantitative model describing the selective solubilization of membrane domains.
AB  - The classical three-stage model of membrane solubilization, including mixed
      membranes, membrane-micelle coexistence, and mixed micelles, is not applicable to
      demixed, domain-forming membranes and must, therefore, fail to describe the
      phenomenon of detergent-resistant membranes (DRMs). In lack of a quantitative
      model, it has often been assumed that ordered, detergent-depleted domains are
      inert, whereas fluid domains are solubilized. We establish a quantitative model
      based on equilibrium thermodynamics that is analogous to the three-stage model
      but comprises three components (two lipids and one detergent) in four phases
      (liquid-ordered and liquid-disordered membranes, micelles, and detergent in
      aqueous solution). For a given set of total concentrations and input parameters
      (initial abundance of ordered domains, solubilization boundaries of the pure
      lipids, etc.), it serves to calculate the phase boundaries and partial
      concentrations of all components in all phases. The results imply that the
      abundance and composition of ordered domains may vary substantially upon addition
      of detergent, both before and during solubilization of the fluid phase. It seems
      that gel-phase or order-preferring lipids are thermodynamically "resistant"
      regardless of the presence of a second, fluid phase. However, thermodynamic or
      kinetic resistance is not sufficient for obtaining DRMs because the resistant
      particles may be too small to be isolated. Cholesterol may be crucial for
      rendering the fragments large enough and, furthermore, enhance the formation of
      ordered domains by nonideal interactions with the detergent.

PMID- 16089478
TI  - Glutathione peroxidase (GPx)-like antioxidant activity of the organoselenium drug
      ebselen: unexpected complications with thiol exchange reactions.
AB  - The factors that are responsible for the relatively low glutathione peroxidase
      (GPx)-like antioxidant activity of organoselenium compounds such as ebselen (1, 2
      phenyl-1,2-benzisoselenazol-3(2H)-one) in the reduction of hydroperoxides with
      aromatic thiols such as benzenethiol and 4-methylbenzenethiol as cosubstrates are
      described. Experimental and theoretical investigations reveal that the relatively
      poor GPx-like catalytic activity of organoselenium compounds is due to the
      undesired thiol exchange reactions that take place at the selenium center in the
      selenenyl sulfide intermediate. This study suggests that any substituent that is
      capable of enhancing the nucleophilic attack of thiol at sulfur in the selenenyl
      sulfide state would enhance the antioxidant potency of organoselenium compounds
      such as ebselen. It is proved that the use of thiol having an intramolecularly
      coordinating group would enhance the biological activity of ebselen and other
      organoselenium compounds. The presence of strong S...N or S...O interactions in
      the selenenyl sulfide state can modulate the attack of an incoming nucleophile
      (thiol) at the sulfur atom of the -Se-S- bridge and enhance the GPx activity by
      reducing the barrier for the formation of the active species selenol.

PMID- 16089479
TI  - Charge propagation in "ion channel sensors" based on protein-modified electrodes
      and redox marker ions.
AB  - The mechanism of charge propagation in "ion channel sensors" (ICSs) consisting of
      gold electrodes modified with a layer of charged proteins and highly charged
      redox-active marker ions in solution was investigated by electrochemical
      techniques, QCM and AFM. The study is based on seven proteins (concanavalin A,
      cytochrome c, glucose oxidase, lysozyme, thyroglobulin, catalase, aldolase, and
      EF1-ATPase) in combination with seven electroactive marker ions ([Fe(CN)6]3-,
      [Fe(CN)6]4-, [Ru(NH3)6]3+, mono-, di-, and trimeric viologens), as well as a
      series of suppressor and enhancer ions leading to the following general
      statements: (i) electrostatic binding of charged marker ions to the domains of
      the protein is a prerequisite for an electrochemical current and (ii) charge
      propagation through the layer consists of electron hopping along surface-confined
      marker ions into the pores between adsorbed proteins. It is further shown that
      (iii) marker ions and suppressor ions with identical charge compete for
      oppositely charged sites on the protein domain, (iv) electrostatically bound
      multilayers of marker or enhancer ions with alternating charge form on a charged
      protein domain, and (v) self-exchange and exergonic ET catalysis between adsorbed
      marker ions and marker ions in solution take place. In addition to fundamental
      insight into the mechanism of charge propagation, valuable information for the
      design, optimization, and tailoring of new biosensors based on the ICS concept is
      demonstrated by the current findings.

PMID- 16089480
TI  - Variable-temperature 19F NMR and theoretical study of 1,9- and 1,7-C60F(CF3) and
      C(s-) and C1-C60F17(CF3): hindered CF3 rotation and through-space J(FF) coupling.
AB  - Milligram amounts of the new compounds 1,9- and 1,7-C60F(CF3) (ca. 85:15 mixture
      of isomers) and C60F3(CF3) were isolated from a high-temperature C60/K2PtF6
      reaction mixture and purified to 98 mol % compositional purity by two-dimensional
      high-performance liquid chromatography using Buckyprep and Buckyclutcher columns.
      The previously observed compounds C60F5(CF3) and C60F7(CF3) were also purified to
      90+ mol % for the first time. Variable-temperature 19F NMR spectra of the mixture
      of C60F(CF3) isomers and the previously reported mixture of C(s)- and C1
      C60F17(CF3) isomers demonstrate for the first time that fullerene(F)n(CF3)m
      derivatives with adjacent F and CF3 substituents exhibit slow-exchange limit
      hindered CF3 rotation spectra at -40 +/- 10 degrees C. The experimental and
      density functional theory (DFT) predicted deltaH++ values for CF3 rotation in 1,9
      C60F(CF3) are 46.8(7) and 46 kJ mol(-1), respectively. The DFT-predicted deltaH++
      values for 1,7-C60F(CF3), C(s)-C60F17(CF3), and C1-C60F17(CF3) are 20, 44, and 54
      kJ mol(-1), respectively. The (> or = 4)J(FF) values from the slow-exchange-limit
      19F spectra, which vary from ca. 0 to 48(1) Hz, show that the dominant nuclear
      spin-spin coupling mechanism is through-space coupling (i.e., direct overlap of
      fluorine atom lone-pair orbitals) rather than coupling through the sigma-bond
      framework. The 2J(FF) values within the CF3 groups vary from 107(1) to 126(1) Hz.
      Collectively, the NMR data provide an unambiguous set of (> or = 4)J(FF) values
      for three different compounds that can be correlated with DFT-predicted or X-ray
      diffraction derived distances and angles and an unambiguous set of 2J(FF) values
      that can serve as an internal standard for all future J(FF) calculations.

PMID- 16089481
TI  - Total synthesis of (-)-spirotryprostatin B: synthesis and related studies.
AB  - The total synthesis of spirotryprostatin B, a cytostatic spiro[pyrrolidine-3,3'
      oxindole] alkaloid, is described. The key step of the synthetic approach consists
      of the application of the MgI2-mediated ring-expansion reaction of a
      spiro[cyclopropane-1,3'-oxindole] with an aldimine, leading to rapid assembly of
      the spirotryprostatin core. The route documents the installation of the prenyl
      side chain by Julia-Kocienski olefination of a key aldehyde precursor, a
      transformation that ultimately allows for facile synthesis of analogues and
      facilitates structure-activity relationships studies.

PMID- 16089482
TI  - Use of parallel synthesis to probe structure-activity relationships among 12
      helical beta-peptides: evidence of a limit on antimicrobial activity.
AB  - We report structure-activity trends among helix-forming beta-amino acid oligomers
      that are intended to mimic alpha-helical host-defense peptides. Parallel
      synthesis of two small, focused beta-peptide libraries allowed us to identify
      relatively short (11-residue) beta-peptides that display antimicrobial activity.
      These beta-peptides exhibit selectivity for bacteria relative to human red blood
      cells. A large hydrophobic helical surface is necessary for antimicrobial
      activity. Longer analogues (16 residues) of the most active library members were
      prepared and evaluated. Some of these longer beta-peptides showed very good
      antimicrobial activity, but none was more active than a previously reported beta
      peptide [Porter, E. A.; Wang, X.; Lee, H.-S.; Weisblum, B.; Gellman, S. H. Nature
      2000, 404, 565]. The extensive literature on alpha-helical host-defense peptides
      and related alpha-peptides indicates that such molecules are seldom active at
      concentrations below 1 microg/mL, and our results suggest that amphiphilic
      helical beta-peptides are subject to a comparable limit.

PMID- 16089483
TI  - Mechanical properties of continuously spun fibers of carbon nanotubes.
AB  - We report on the mechanical properties of fibers consisting of pure carbon
      nanotube fibers directly spun from an aerogel formed during synthesis by chemical
      vapor deposition. The continuous withdrawal of product from the gas phase imparts
      a high commercial potential to the process, either for the production of
      particularly strong fibers or for the economic production of bulk quantities of
      carbon nanotubes. Tensile tests were performed on fibers produced from the
      dissociation of three different hydrocarbons, namely, ethanol, ethylene glycol,
      and hexane, with a range of iron (catalyst) concentrations. The conditions were
      chosen to lie within the range known to enable satisfactory continuous spinning,
      the iron concentration being varied within this range. Increasing proportions of
      single wall nanotubes were found as the iron concentration was decreased,
      conditions which also produced fibers of best strength and stiffness. The maximum
      tensile strength obtained was 1.46 GPa (equivalent to 0.70 N/tex assuming a
      density of 2.1 g/cm(3)). The experiments indicate that significant improvements
      in the mechanical properties can be accomplished by optimizing the process
      conditions.

PMID- 16089484
TI  - Gradient chemical micro patterns: a reference substrate for surface
      nanometrology.
AB  - We present fabrication routes for a new type of surface specimen that exhibits a
      micro pattern with a gradient in chemical contrast between the pattern domains.
      Design elements in the specimen allow chemical contrast in the micro pattern to
      be related to well-established surface characterization data, such as contact
      angle measurements. These gradient specimens represent a reference tool for
      calibrating image contrast in chemically sensitive scanning probe microscopy
      techniques and a platform for the high-throughput analysis of polymer thin film
      behavior.

PMID- 16089485
TI  - Transformation of self-assembled InAs/InP quantum dots into quantum rings without
      capping.
AB  - Transformation of self-assembled InAs quantum dots (QDs) on InP(100) into quantum
      rings (QRs) is studied. In contrast to the typical approach to III--V
      semiconductor QR growth, the QDs are not capped to form rings. Atomic force
      micrographs reveal a drastic change from InAs QDs into rings after a growth
      interruption in tertiarybutylphosphine ambient. Strain energy relief in the InAs
      QD is discussed and a mechanism for dot-to-ring transformation by As/P exchange
      reactions is proposed.

PMID- 16089486
TI  - Nanostructuring titania by embossing with polymer molds made from anodic alumina
      templates.
AB  - We demonstrate a method for embossing titania sol--gel precursor with poly(methyl
      methacrylate) (PMMA) molds to make thin films of titania that have dense arrays
      of 35--65 nm diameter pores, whose features are 1 order of magnitude smaller than
      those previously demonstrated for sol--gel molding. We show that the high modulus
      of PMMA is necessary to preserve small features with high aspect ratios on the
      mold for nanopatterning. The molds are prepared by thermally infiltrating PMMA
      into anodic alumina templates, whose pore dimensions and depths are adjustable by
      varying anodization conditions. The difficulties associated with mold release
      from a master are avoided by wet etching the template. These titania films, and
      others made with other semiconductors, could be useful for photovoltaic,
      photocatalytic, and sensing applications where nanostructuring of surfaces with
      controlled dimensions are essential.

PMID- 16089487
TI  - First-principles simulations of inelastic electron tunneling spectroscopy of
      molecular electronic devices.
AB  - Inelastic electron tunneling spectroscopy (IETS) is a powerful experimental tool
      for studying the molecular and metal contact geometries in molecular electronic
      devices. A first-principles computational method based on the hybrid density
      functional theory is developed to simulate the IETS of realistic molecular
      electronic devices. The calculated spectra of a real device with an
      octanedithiolate embedded between two gold contacts are in excellent agreement
      with recent experimental results. Strong temperature dependence of the
      experimental IETS spectra is also reproduced. It is shown that the IETS is
      extremely sensitive to the intramolecular conformation and the molecule-metal
      contact geometry changes. With the help of theoretical calculations, it has
      finally become possible to fully understand and assign the complicated
      experimental IETS and, more importantly, provide the structural information of
      the molecular electronic devices.

PMID- 16089488
TI  - Large enhancement of fluorescence efficiency from CdSe/ZnS quantum dots induced
      by resonant coupling to spatially controlled surface plasmons.
AB  - Nanoengineered fluorescent response is reported from semiconductor core-shell
      (CdSe/ZnS) quantum dots in proximity to the surface plasmon polariton field of
      periodic Ag nanoparticle arrays. Tuning the surface plasmon polariton resonance
      to the quantum dot exciton emission band results in an enhancement of up to
      approximately 50-fold in the overall fluorescence efficiency, in a design where
      each Ag nanoparticle is interconnected by a continuous Ag thin film. Propagating
      modes of surface plasmon resonances have a direct impact on the fluorescence
      enhancement.

PMID- 16089489
TI  - Visualization of individual single-walled carbon nanotubes by fluorescent polymer
      wrapping.
AB  - Manipulating optical properties of single-walled nanotubes (SWNTs) is necessary
      for the development of nanoscale optical devices and probes for biomedical
      research. In life sciences it will make possible the direct observation of SWNTs
      inside living cells using optical microscopes. In the nanotechnology field it
      will enable the development of nanosensors with fluorescent reporting. However,
      the direct fluorescent labeling of SWNTs is obstructed by their strong light
      quenching qualities. Besides, chemical functionalization of SWNTs needed for the
      covalent attachment of fluorescent dyes could change favorable properties of
      nanotubes. Here we report that optical properties of SWNTs can be manipulated
      without their covalent modification by wrapping them with fluorescently labeled
      polymer poly(vinylpyrrolidone) (PVP-1300). Fluorescent PVP-1300 forms a
      monomolecular approximately 2.5 nm thick layer coiling around individual SWNTs
      and nanotube bundles. PVP casing is fluorescent although it is only several
      nanometers thick. This makes individual SWNTs observable by a fluorescent
      microscope. The spare polymer strands left over after wrapping around the
      relatively shorter nanotubes form junctions between SWNTs tying them together
      into new configurations, primarily Y- and psi-type junctions. The ability to use
      a single fluorescent polymer strand to fasten nanotubes together can be useful in
      assembly of nanotube-made devices. In PVP-covered SWNTs multiple fluorophores are
      attached to each single nanotube making them unique composite fluorophores
      attractive as parts of biological fluorescent probes and in the development of
      the new materials in photonics and nanotechnology.

PMID- 16089490
TI  - Surface-enhanced Raman scattering from individual au nanoparticles and
      nanoparticle dimer substrates.
AB  - Surface-enhanced Raman scattering (SERS) intensities for individual Au
      nanospheres, nanoshells, and nanosphere and nanoshell dimers coated with
      nonresonant molecules are measured, where the precise nanoscale geometry of each
      monomer and dimer is identified through in situ atomic force microscopy. The
      observed intensities correlate with the integrated quartic local electromagnetic
      field calculated for each specific nanostructure geometry. In this study, we find
      that suitably fabricated nanoshells can provide SERS enhancements comparable to
      nanosphere dimers.

PMID- 16089491
TI  - Metal--semiconductor transition in single-walled carbon nanotubes induced by low
      energy electron irradiation.
AB  - We report the effect of low-energy (1 keV) electron beam irradiation on gated,
      three-terminal devices constructed from metallic single-walled carbon nanotubes.
      Pristine devices, which exhibited negligible gate voltage response at room
      temperature and metallic single-electron transistor characteristics at low
      temperatures, when exposed to an electron beam, exhibited ambipolar field effect
      transistor (room temperature) and single-electron transistor (low temperature)
      characteristics. This metal-semiconductor transition is attributed to
      inhomogeneous electric fields arising from charging during electron irradiation.

PMID- 16089492
TI  - Electric field induced switching of the fluorescence of single semiconductor
      quantum rods.
AB  - The exceptional fluorescence properties of single CdSe quantum rods (QRs) arising
      from internal and external electric fields are studied. Reversible external field
      induced switching of the emission in single QRs is reported for the first time.
      This effect was correlated with local field induced emission intensity reduction
      and newly observed darkening mechanism. Bimodal spectral jumps under a zero field
      were also observed and assigned to charged exciton emission, a phenomenon that
      was likewise directly controlled through an external field. These phenomena point
      to the use of single QRs as spectrally tunable charge sensitive fluorophores with
      polarized emission in fluorescence tagging and optical switching applications.

PMID- 16089493
TI  - Ferromagnetic GaN--Cr Nanowires.
AB  - Using first-principles theory, we predict ferromagnetism in Cr-doped GaN
      nanowires irrespective of the sites that the Cr atoms occupy. This is in contrast
      to Mn-doped GaN nanowires in which the magnetic coupling between the Mn atoms is
      sensitive to the Mn--Mn and Mn--N distances, although the ground state of Mn
      doped GaN nanowires is ferromagnetic. Each Cr atom carries a magnetic moment of
      about 2.5 micro(B). The magnetic moment at the N site, however, is small and is
      aligned antiferromagnetically to the moments at the Cr atom. The magnetization
      axis is perpendicular to the axis of the wire, but the anisotropy energy is
      rather small. The easy solubility of Cr in GaN and the lack of sensitivity of
      ferromagnetic coupling to Cr distribution suggest that Cr-doped GaN nanowires may
      be a more suitable system for applications in spintronics than Mn-doped GaN
      nanowires.

PMID- 16089494
TI  - Periodic nanovoid structures via femtosecond laser irradiation.
AB  - We have observed periodically aligned nanovoid structures inside a conventional
      borosilicate glass induced by a single femtosecond (fs) laser beam for the first
      time, to our knowledge. The spherical voids of nanosized diameter were aligned
      spontaneously with a period along the propagation direction of the laser beam.
      The period, the number of voids, and the whole length of the aligned void
      structure were controlled by changing the laser power, the pulse number, and the
      position of the focal point.

PMID- 16089495
TI  - Blue electroluminescence from oxadiazole grafted poly(phenylene-ethynylene)s.
AB  - Blue poly(phenylene-ethynylene) (PPE) electroluminescence is achieved in a single
      layer organic light emitting device. The polymeric system consists of an
      oxadiazole grafted PPE, which combines the necessary charge transport properties
      while maintaining the desirable efficient, narrow light-emitting properties of
      the PPE. Incorporation of a pentiptycene scaffold within the PPE structure
      prevents ground-state and excited-state interactions between the pendent
      oxadiazole units and the conjugated backbone.

PMID- 16089496
TI  - Fabrication of high-aspect-ratio Prussian blue nanotubes using a porous alumina
      template.
AB  - Prussian blue nanotubes were fabricated by using a sequential deposition
      technique inside the 60-nm well-ordered pores of anodic alumina. By varying the
      deposition parameters and the dimensions of the template, we could tailor the
      length and the outer as well as the inner diameter of the tubes. The nanotubes
      were characterized using scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), and X-ray diffraction (XRD).

PMID- 16089497
TI  - Hydrophobicity, adhesion, and friction properties of nanopatterned polymers and
      scale dependence for micro- and nanoelectromechanical systems.
AB  - Applications in micro/nanoelectromechanical systems generally require low
      adhesion and friction values between two materials of interest. By alteration of
      the material combinations and surface roughness, including nanopatterning,
      adhesion and friction can be tailored to meet a specific requirement. Surfaces
      found in nature, such as hydrophobic lotus leaves, provide a good example of this
      optimization. Recent models of hydrophobic leaf surfaces show a correlation
      between roughness and hydrophobicity, which can be mimicked by the presence of
      nanopatterned asperities on a polymer surface. In addition, by introducing
      nanopatterns on the polymer surface, the real area of contact decreases when
      another surface comes into contact with the patterned surface, which reduces
      adhesion and friction. This study explores the effect of nanopatterning on
      hydrophobicity, adhesion, and friction for two different hydrophilic polymers,
      poly(methyl methacrylate) (PMMA) and polyurethane acrylate (MINS), with two types
      of patterned asperities, low aspect ratio and high aspect ratio, investigated by
      use of an atomic/friction force microscope (AFM/FFM). In addition to the
      polymers, a hydrophobic coating was deposited on the surface of the patterned
      PMMA to study the effect of roughness on the contact angle, along with adhesion
      and friction. Relative contribution due to change in contact angle and real area
      of contact are explored. Scale dependence on adhesion and friction was also
      studied using AFM tips of various radii. Since applications of these surfaces
      will require operation in varying environments, the effect of relative humidity
      is investigated.

PMID- 16089498
TI  - Self-assembled lipid superstructures: beyond vesicles and liposomes.
AB  - A unique set of nanoparticle dispersions of self-assembled lipid mesophases with
      distinctive reversed cubic, hexagonal, and sponge phase structures has been
      prepared by use of original lipid combinations and a simple, generally applicable
      and scalable method. All key properties, particle size distributions, shape,
      phase structure, and stability, are controlled predictably and reproducibly. The
      results suggest the cross-disciplinary use of nonlamellar particle structures in
      science and technology as, for instance, biomimetics, in vivo drug delivery
      vehicles for diagnostic and therapeutic agents, protein crystallization matrices,
      and soft nanoporous materials.

PMID- 16089499
TI  - Density functional theory study of optical transitions in semiconducting single
      walled carbon nanotubes.
AB  - We present a density functional theory study of optical transitions in
      semiconducting single-walled carbon nanotubes. We utilize recently developed
      exchange-correlation functionals in a set of 21 tubes that includes large and
      chiral nanotubes. The novel TPSSh meta-generalized gradient approximation hybrid
      functional accurately reproduces optical excitations with mean absolute errors of
      0.024 and 0.065 eV for first and second transitions, respectively. We also report
      predictions for higher order optical transitions.

PMID- 16089500
TI  - Mechanisms of 1D crystal growth in reactive vapor transport: indium nitride
      nanowires.
AB  - Indium nitride (InN) nanowire synthesis using indium (In) vapor transport in a
      dissociated ammonia environment (reactive vapor transport) is studied in detail
      to understand the nucleation and growth mechanisms involved with the so-called
      "self-catalysis" schemes. The results show that the nucleation of InN crystal
      occurs first on the substrate. Later, In droplets are formed on top of the InN
      crystals because of selective wetting of In onto InN crystals. Further growth via
      liquid-phase epitaxy through In droplets leads the growth in one dimension (1D),
      resulting in the formation of InN nanowires. The details about the nucleation and
      growth aspects within these self-catalysis schemes are rationalized further by
      demonstrating the growth of heteroepitaxially oriented nanowire arrays on single
      crystal substrates and "tree-like" morphologies on a variety of substrates.
      However, the direct nitridation of In droplets using dissociated ammonia results
      in the spontaneous nucleation and basal growth of nanowires directly from the In
      melt surface, which is quite different from the above-mentioned nucleation
      mechanism with the reactive vapor transport case. The InN nanowires exhibit a
      band gap of 0.8 eV, whereas the mixed phase of InN and In(2)O(3) nanowires
      exhibit a peak at approximately 1.9 eV in addition to that at 0.8 eV.

PMID- 16089501
TI  - Decreased insulin-stimulated ATP synthesis and phosphate transport in muscle of
      insulin-resistant offspring of type 2 diabetic parents.
AB  - BACKGROUND: Insulin resistance is the best predictor for the development of type
      2 diabetes. Recent studies have shown that young, lean, insulin-resistant (IR)
      offspring of parents with type 2 diabetes have reduced basal rates of muscle
      mitochondrial phosphorylation activity associated with increased intramyocellular
      lipid (IMCL) content, which in turn blocks insulin signaling and insulin action
      in muscle. In order to further characterize mitochondrial activity in these
      individuals, we examined insulin-stimulated rates of adenosine triphosphate (ATP)
      synthesis and phosphate transport in skeletal muscle in a similar cohort of
      participants. METHODS AND FINDINGS: Rates of insulin-stimulated muscle
      mitochondrial ATP synthase flux and insulin-stimulated increases in
      concentrations of intramyocellular inorganic phosphate (Pi) were assessed by 31P
      magnetic resonance spectroscopy (MRS) in healthy, lean, IR offspring of parents
      with type 2 diabetes and healthy, lean control participants with normal insulin
      sensitivity. IMCL content in the soleus muscle of all participants was assessed
      by 1H MRS. During a hyperinsulinemic-euglycemic clamp, rates of insulin
      stimulated glucose uptake were decreased by approximately 50% in the IR offspring
      compared to the control participants (p = 0.007 versus controls) and were
      associated with an approximately 2-fold increase in IMCL content (p < 0.006
      versus controls). In the control participants rates of ATP synthesis increased by
      approximately 90% during the hyperinsulinemic-euglycemic clamp. In contrast,
      insulin-stimulated rates of muscle mitochondrial ATP synthesis increased by only
      5% in the IR offspring (p = 0.001 versus controls) and was associated with a
      severe reduction of insulin-stimulated increases in the intramyocellular Pi
      concentrations (IR offspring: 4.7% +/- 1.9% versus controls: 19.3% +/- 5.7%; p =
      0.03). Insulin-induced increases in intramyocellular Pi concentrations correlated
      well with insulin-stimulated increases in rates of ATP synthesis (r = 0.67; p =
      0.008). CONCLUSIONS: These data demonstrate that insulin-stimulated rates of
      mitochondrial ATP synthesis are reduced in IR offspring of parents with type 2
      diabetes. Furthermore, these IR offspring also have impaired insulin-stimulated
      phosphate transport in muscle, which may contribute to their defects in insulin
      stimulated rates of mitochondrial ATP synthesis.

PMID- 16089502
TI  - Functional analysis of human hematopoietic stem cell gene expression using
      zebrafish.
AB  - Although several reports have characterized the hematopoietic stem cell (HSC)
      transcriptome, the roles of HSC-specific genes in hematopoiesis remain elusive.
      To identify candidate regulators of HSC fate decisions, we compared the
      transcriptome of human umbilical cord blood and bone marrow (CD34+)(CD33-)(CD38
      )Rho(lo)(c-kit+) cells, enriched for hematopoietic stem/progenitor cells with
      (CD34+)(CD33-)(CD38-)Rho(hi) cells, enriched in committed progenitors. We
      identified 277 differentially expressed transcripts conserved in these
      ontogenically distinct cell sources. We next performed a morpholino antisense
      oligonucleotide (MO)-based functional screen in zebrafish to determine the
      hematopoietic function of 61 genes that had no previously known function in HSC
      biology and for which a likely zebrafish ortholog could be identified. MO knock
      down of 14/61 (23%) of the differentially expressed transcripts resulted in
      hematopoietic defects in developing zebrafish embryos, as demonstrated by altered
      levels of circulating blood cells at 30 and 48 h postfertilization and
      subsequently confirmed by quantitative RT-PCR for erythroid-specific hbae1 and
      myeloid-specific lcp1 transcripts. Recapitulating the knockdown phenotype using a
      second MO of independent sequence, absence of the phenotype using a mismatched MO
      sequence, and rescue of the phenotype by cDNA-based overexpression of the
      targeted transcript for zebrafish spry4 confirmed the specificity of MO targeting
      in this system. Further characterization of the spry4-deficient zebrafish embryos
      demonstrated that hematopoietic defects were not due to more widespread defects
      in the mesodermal development, and therefore represented primary defects in HSC
      specification, proliferation, and/or differentiation. Overall, this high
      throughput screen for the functional validation of differentially expressed genes
      using a zebrafish model of hematopoiesis represents a major step toward obtaining
      meaningful information from global gene profiling of HSCs.

PMID- 16089504
TI  - Comment on "Recent origin and cultural reversion of a hunter-gatherer group".

PMID- 16089503
TI  - Structure of a pheromone receptor-associated MHC molecule with an open and empty
      groove.
AB  - Neurons in the murine vomeronasal organ (VNO) express a family of class Ib major
      histocompatibility complex (MHC) proteins (M10s) that interact with the V2R class
      of VNO receptors. This interaction may play a direct role in the detection of
      pheromonal cues that initiate reproductive and territorial behaviors. The crystal
      structure of M10.5, an M10 family member, is similar to that of classical MHC
      molecules. However, the M10.5 counterpart of the MHC peptide-binding groove is
      open and unoccupied, revealing the first structure of an empty class I MHC
      molecule. Similar to empty MHC molecules, but unlike peptide-filled MHC proteins
      and non-peptide-binding MHC homologs, M10.5 is thermally unstable, suggesting
      that its groove is normally occupied. However, M10.5 does not bind endogenous
      peptides when expressed in mammalian cells or when offered a mixture of class I
      binding peptides. The F pocket side of the M10.5 groove is open, suggesting that
      ligands larger than 8-10-mer class I-binding peptides could fit by extending out
      of the groove. Moreover, variable residues point up from the groove helices,
      rather than toward the groove as in classical MHC structures. These data suggest
      that M10s are unlikely to provide specific recognition of class I MHC-binding
      peptides, but are consistent with binding to other ligands, including proteins
      such as the V2Rs.

PMID- 16089506
TI  - Prices for ingenuity.

PMID- 16089507
TI  - The left-right polarity puzzle: determining embryonic handedness.

PMID- 16089508
TI  - Bioinformatics and data management support for environmental genomics.

PMID- 16089509
TI  - Theory of enhanced performance emerging in a sparsely connected competitive
      population.
AB  - We provide an analytic theory to explain Anghel et al's recent numerical finding
      whereby a maximum in the global performance emerges for a sparsely connected
      competitive population [Phys. Rev. Lett. 92, 058701 (2004)]. We show that the
      effect originates in the highly correlated dynamics of strategy choice, and can
      be significantly enhanced using a simple modification to the model.

PMID- 16089510
TI  - Phase diagram of the Gaussian-core model.
AB  - We trace with high numerical accuracy the phase diagram of the Gaussian-core
      model, a classical system of point particles interacting via a Gaussian-shaped,
      purely repulsive potential. This model, which provides a reliable qualitative
      description of the thermal behavior of interpenetrable globular polymers, is
      known to exhibit a polymorphic fcc-bcc transition at low densities and reentrant
      melting at high densities. Extensive Monte Carlo simulations, carried out in
      conjunction with accurate calculations of the solid free energies, lead to a
      thermodynamic scenario that is partially modified with respect to previous
      knowledge. In particular, we find that: (i) the fluid-bcc-fcc triple-point
      temperature is about one third of the maximum freezing temperature; (ii) upon
      isothermal compression, the model exhibits a fluid-bcc-fcc-bcc-fluid sequence of
      phases in a narrow range of temperatures just above the triple point. We discuss
      these results in relation to the behavior of star-polymer solutions and of other
      softly repulsive systems.

PMID- 16089511
TI  - Large equilibrium clusters in low-density aqueous suspensions of polyelectrolyte
      liposome complexes: a phenomenological model.
AB  - In this paper, we revisit some of our previous results together with further
      experimental evidences for the existence of large equilibrium clusters in low
      density aqueous colloidal suspensions, resulting from the screening of charged
      spherical macroions by oppositely charged linear polyelectrolytes. The
      aggregation process is described by a simple phenomenological model where
      aggregates interact via a long-range repulsion Yukawa potential and some supports
      to the equilibrium properties of the resulting aggregates, on the basis of
      dynamic light scattering, zeta potential, and transmission electron microscopy
      techniques, have been provided.

PMID- 16089512
TI  - Identification of a wagging vibrational mode of water molecules at the
      water/vapor interface.
AB  - An improved time correlation function description of sum frequency generation
      (SFG) spectroscopy was applied to theoretically describe the water/vapor
      interface. The resulting spectra compare favorably in shape and relative
      magnitude to extant experimental results in the O-H stretching region of water.
      Further, the SFG spectra show a well-defined intermolecular mode at 875 cm(-1)
      that has significant intensity. The resonance is due to a wagging mode localized
      on a single water molecule. It represents a well-defined population of water
      molecules at the interface that, along with the free O-H modes, represent the
      dominant interfacial species.

PMID- 16089513
TI  - Molecular dynamics simulation study of the alpha- and beta-relaxation processes
      in a realistic model polymer.
AB  - Molecular dynamics simulations of a melt of freely rotating chains of 1,4
      polybutadiene (FRC-PBD) have been performed over a wide range of temperature.
      Removal of the dihedral barriers in FRC-PBD allows for complete resolution of the
      Johari-Goldstein beta process from the primary alpha process in the simulation
      time window. We find that relaxation in the beta regime occurs as the result of
      large-angle excursions of all backbone dihedrals. While during the beta process
      each dihedral visits all available states, the complete relaxation of torsional
      autocorrelation function (alpha process) occurs only when the polymer matrix
      shows significant motion and each dihedral populates all states with equilibrium
      probability.

PMID- 16089515
TI  - Quantifying signals with power-law correlations: a comparative study of detrended
      fluctuation analysis and detrended moving average techniques.
AB  - Detrended fluctuation analysis (DFA) and detrended moving average (DMA) are two
      scaling analysis methods designed to quantify correlations in noisy nonstationary
      signals. We systematically study the performance of different variants of the DMA
      method when applied to artificially generated long-range power-law correlated
      signals with an a priori known scaling exponent alpha(0) and compare them with
      the DFA method. We find that the scaling results obtained from different variants
      of the DMA method strongly depend on the type of the moving average filter.
      Further, we investigate the optimal scaling regime where the DFA and DMA methods
      accurately quantify the scaling exponent alpha(0) , and how this regime depends
      on the correlations in the signal. Finally, we develop a three-dimensional
      representation to determine how the stability of the scaling curves obtained from
      the DFA and DMA methods depends on the scale of analysis, the order of
      detrending, and the order of the moving average we use, as well as on the type of
      correlations in the signal.

PMID- 16089514
TI  - Pattern formation of microtubules and motors: inelastic interaction of polar
      rods.
AB  - We derive a model describing spatiotemporal organization of an array of
      microtubules interacting via molecular motors. Starting from a stochastic model
      of inelastic polar rods with a generic anisotropic interaction kernel we obtain a
      set of equations for the local rods concentration and orientation. At large
      enough mean density of rods and concentration of motors, the model describes
      orientational instability. We demonstrate that the orientational instability
      leads to the formation of vortices and (for large density and/or kernel
      anisotropy) asters seen in recent experiments.

PMID- 16089516
TI  - Statistical theory of noble-gas crystals and the phenomenon of sublimation.
AB  - We propose a consistent (without any fitting parameters) statistical theory of
      classical noble-gas crystals with pair interaction between atoms. Using the
      equation for the single-particle distribution function of the statistical system,
      we demonstrate the existence of an infinite number of exact sum rules for the
      amplitudes of the space-periodic solutions. Even the first sum rule leads to the
      solution which turns into the exact one at the absolute zero temperature. For the
      pair distribution function, we obtained the physically correct solution using the
      well-known exact relation for the compressibility as the self-consistent
      condition. As a result, we succeeded in recovering the equation of state of the
      crystal, and starting from the Lennard-Jones potential with the "gaseous"
      parameters, we calculated the temperature dependencies of the lattice constant
      and the isothermal compressibility of the crystal at the sublimation line. These
      calculations (including the form of the sublimation line itself) agree rather
      well with the corresponding experimental data for the argon-type media in the
      "classical" temperature region. The question about the bifurcation of the
      solutions is considered. Ways to further develop the theory are discussed.

PMID- 16089517
TI  - Canonical quantization of nonlinear many-body systems.
AB  - We study the quantization of a classical system of interacting particles obeying
      a recently proposed kinetic interaction principle (KIP) [G. Kaniadakis, Physica A
      296, 405 (2001)]. The KIP fixes the expression of the Fokker-Planck equation
      describing the kinetic evolution of the system and imposes the form of its
      entropy. In the framework of canonical quantization, we introduce a class of
      nonlinear Schrodinger equations (NSEs) with complex nonlinearities, describing,
      in the mean-field approximation, a system of collectively interacting particles
      whose underlying kinetics is governed by the KIP. We derive the Ehrenfest
      relations and discuss the main constants of motion arising in this model. By
      means of a nonlinear gauge transformation of the third kind, it is shown that in
      the case of constant diffusion and linear drift, the class of NSEs obeying the
      KIP is gauge-equivalent to another class of NSEs containing purely real
      nonlinearities depending only on the field rho=|psi|(2) .

PMID- 16089518
TI  - Reaction-diffusion wave fronts on comblike structures.
AB  - From the Hamilton-Jacobi formalism, an explicit expression for the speed of wave
      front propagation along the backbone of comblike structures is obtained. This
      expression, through the waiting-time distribution function, takes into account
      the number of sites and their distribution in the secondary branches. Our
      theoretical results are supported by numerical simulations of the reaction random
      walk process on the structure. Finally, a more complex situation such as the
      Peano basin structure is also considered, both theoretically and numerically,
      exhibiting a good agreement too.

PMID- 16089519
TI  - Point process model of 1/f noise vs a sum of Lorentzians.
AB  - We present a simple point process model of 1/f(beta) noise, covering different
      values of the exponent beta . The signal of the model consists of pulses or
      events. The interpulse, interevent, interarrival, recurrence, or waiting times of
      the signal are described by the general Langevin equation with the multiplicative
      noise and stochastically diffuse in some interval resulting in a power-law
      distribution. Our model is free from the requirement of a wide distribution of
      relaxation times and from the power-law forms of the pulses. It contains only one
      relaxation rate and yields 1/f(beta) spectra in a wide range of frequencies. We
      obtain explicit expressions for the power spectra and present numerical
      illustrations of the model. Further we analyze the relation of the point process
      model of 1/f noise with the Bernamont-Surdin-McWhorter model, representing the
      signals as a sum of the uncorrelated components. We show that the point process
      model is complementary to the model based on the sum of signals with a wide-range
      distribution of the relaxation times. In contrast to the Gaussian distribution of
      the signal intensity of the sum of the uncorrelated components, the point process
      exhibits asymptotically a power-law distribution of the signal intensity. The
      developed multiplicative point process model of 1/f(beta)noise may be used for
      modeling and analysis of stochastic processes in different systems with the power
      law distribution of the intensity of pulsing signals.

PMID- 16089520
TI  - Anisotropy of the magnetoviscous effect in ferrofluids.
AB  - The anisotropy of the magnetoviscous effect in ferrofluids subjected to weak
      planar Couette flow is investigated by extensive molecular simulations. The field
      and concentration dependence of the viscosity coefficients are found to depend on
      the relative orientation of the magnetic field with respect to the flow geometry.
      Comparison with dynamical mean-field models shows satisfactory agreement for
      moderate interaction strengths. In the semidilute regime it is found that the
      anisotropy contains valuable information on particle interaction.

PMID- 16089521
TI  - Quantum drag forces on a sphere moving through a rarefied gas.
AB  - As an application of quantum fluid mechanics, we consider the drag force exerted
      on a sphere by an ultradilute gas. Quantum mechanical diffraction scattering
      theory enters in that regime wherein the mean free path of a molecule in the gas
      is large compared with the sphere radius. The drag force is computed in a model
      specified by the "sticking fraction" of events in which a gaseous molecule is
      adsorbed by the spherical surface. Classical inelastic scattering theory is shown
      to be inadequate for physically reasonable sticking fraction values. The quantum
      mechanical scattering drag force is exhibited theoretically and compared with
      experimental data.

PMID- 16089522
TI  - Combined size and density segregation and mixing in noncircular tumblers.
AB  - Flowing granular materials segregate due to differences in particle size (driven
      by percolation) and density (driven by buoyancy). For noncircular tumblers the
      additional interaction between the segregation mechanisms and chaotic advection
      complicates the physics. Experiments are performed using a bi-disperse mixture of
      equal volumes of different sizes of steel and glass beads in a quasi-two
      dimensional square tumbler. Mixing is observed instead of segregation when the
      denser beads are larger than the lighter beads so that the ratio of particle
      sizes is greater than the ratio of particle densities. This can be expressed in
      terms of the particle diameters and masses as d(heavy)/d(light)
      >(m(heavy)/m(light))(1/4) . Segregation patterns vary from a semicircular core
      when the fill level is below 50% to more complicated patterns including lobes and
      streaks for fill levels above 50%. Temporal evolution of segregated patterns is
      quantified in terms of a "segregation index" (based on the area of the segregated
      pattern) to capture both the rate and extent of segregation at different particle
      properties. The circular and noncircular tumblers have no significant difference
      in the segregation index, even though the segregation patterns differ
      significantly.

PMID- 16089523
TI  - Failure of a granular step.
AB  - We investigate the gravity driven rapid failure of a granular step composed of
      noncohesive steel beads. The step is initially held together with electromagnets,
      and released when the current is switched off. We visualize the surface and the
      motion of the grains during the entire relaxation. The initial failure occurs at
      the surface and the subsequent flow is also confined to the surface as the step
      relaxes to its final state. The final shape of the surface is almost linear,
      depends on the initial angle of the step, and is not sensitive to the size of the
      grains. The average final slope of the pile is only slightly lower than the angle
      of repose of a pile formed by slowly pouring particles on to a flat surface. The
      evolution of the step is compared with a proposed convective-diffusion model of
      our system. The qualitative features of the relaxation are captured by the model
      after a flow-dependent dissipation parameter is introduced.

PMID- 16089524
TI  - Jamming during the discharge of granular matter from a silo.
AB  - In this work, we present an experimental study of the jamming that stops the free
      flow of grains from a silo discharging by gravity. When the outlet size is not
      much bigger than the beads, granular material jams the outlet of the container
      due to the formation of an arch. Statistical data from the number of grains
      fallen between consecutive jams are presented. The information that they provide
      can help one to understand the jamming phenomenon. As the ratio between the size
      of the orifice and the size of the beads is increased, the probability that an
      arch blocks the outlet decreases. We show here that there is a power-law
      divergence of the mean avalanche size for a finite critical radius. Beyond this
      critical radius, no jamming can occur and the flow is never stopped. The
      dependence of the arch formation on the shape and the material of the grains has
      been explored. It has been found that the material properties of the grains do
      not affect the arch formation probability. On the contrary, the shape of the
      grains deeply influences it. A simple model to interpret the results is also
      discussed.

PMID- 16089525
TI  - Role of anisotropy in the elastoplastic response of a polygonal packing.
AB  - We study the effect of the anisotropy induced by loading on the elastoplastic
      response of a two dimensional discrete element model granular material. The
      anisotropy of the contact network leads to a breakdown of the linear isotropic
      elasticity. We report on a linear dependence of the Young moduli and Poisson
      ratios on the fabric coefficients, measuring the anisotropy of the contact
      network. The resulting nonassociated plastic flow rule and the linear
      relationship between dilatancy and stress ratio are discussed in terms of several
      existing models. We propose a paradigm for understanding soil plasticity, based
      on the correlation between the plastic flow rule and the induced anisotropy on
      the subnetwork of sliding contacts.

PMID- 16089526
TI  - Penetration depth for shallow impact cratering.
AB  - We present data for the penetration of a variety of spheres, dropped from rest,
      into a loose noncohesive granular medium. We improve upon earlier work [J. S.
      Uehara, Phys. Rev. Lett. 90, 194301 (2003)] in three regards. First, we explore
      the behavior vs sphere diameter and density more systematically, by holding one
      of these parameters constant while varying the other. Second, we prepare the
      granular medium more reproducibly and, third, we measure the penetration depth
      more accurately. The new data support the previous conclusion that the
      penetration depth is proportional to the 1/2 power of sphere density, the 2/3
      power of sphere diameter, and the 1/3 power of total drop distance.

PMID- 16089527
TI  - Boltzmann equation for a granular capped rectangle in a thermalized bath of hard
      disks.
AB  - By using the Boltzmann approach, we study the steady-state dynamics of a granular
      capped rectangle placed in a two-dimensional bath of thermalized hard disks. Hard
      core collisions are assumed elastic between disks and inelastic between the
      capped rectangle and the disks, with a normal coefficient of restitution alpha <
      1. Assuming a Gaussian ansatz for the probability distribution functions, we
      obtain analytical expressions for the granular temperatures. We show the absence
      of equipartition and investigate both the role of the anisotropy of the capped
      rectangle and of the relative ratio of the bath particles to the linear sizes of
      the capped rectangle. In addition, we investigate a model of a capped rectangle
      with two normal coefficients of restitution for collisions along the straight and
      curved surfaces of the capped rectangle. In this case one observes equipartition
      for a nontrivial ratio of the normal coefficient of restitutions.

PMID- 16089528
TI  - Self-stresses and crack formation by particle swelling in cohesive granular
      media.
AB  - We present a molecular-dynamics study of force patterns, tensile strength, and
      crack formation in a cohesive granular model where the particles are subjected to
      swelling or shrinkage gradients. Nonuniform particle size change generates self
      equilibrated forces that lead to crack initiation as soon as the strongest
      tensile contacts begin to fail. We find that the tensile strength is well below
      the theoretical strength as a result of inhomogeneous force transmission in
      granular media. The cracks propagate either inward from the edge upon shrinkage
      or outward from the center upon swelling. We show that the coarse-grained
      stresses are correctly predicted by an elastic model that incorporates particle
      size change as metric evolution.

PMID- 16089529
TI  - Effective capillary interaction of spherical particles at fluid interfaces.
AB  - We present a detailed analysis of the effective force between two smooth
      spherical colloids floating at a fluid interface due to deformations of the
      interface in an inhomogeneous pressure field. The results hold in general and are
      applicable independently of the source of the deformation provided the capillary
      deformations are small so that a superposition approximation for the deformations
      is valid. We conclude that an effective long-ranged attraction is possible if the
      net force on the system does not vanish. Otherwise, the interaction is short
      ranged and cannot be computed reliably based on the superposition approximation.
      As an application, we consider the case of like-charged, smooth nanoparticles and
      electrostatically induced capillary deformation. The resulting long-ranged
      capillary attraction can be easily tuned by a relatively small external
      electrostatic field, but it cannot explain recent experimental observations of
      attraction if these experimental systems were indeed isolated.

PMID- 16089530
TI  - Morphological transition between diffusion-limited and ballistic aggregation
      growth patterns.
AB  - In this work, the transition between diffusion-limited (DLA) and ballistic
      aggregation (BA) models was reconsidered using a model in which biased random
      walks simulate the particle trajectories. The bias is controlled by a parameter
      lambda, which assumes the value lambda=0 (1) for the ballistic (diffusion
      limited) aggregation model. Patterns growing from a single seed were considered.
      In order to simulate large clusters, an efficient algorithm was developed. For
      lambda (not equal to) 0 , the patterns are fractal on small length scales, but
      homogeneous on large ones. We evaluated the mean density of particles (-)rho in
      the region defined by a circle of radius r centered at the initial seed. As a
      function of r, (-)rho reaches the asymptotic value rho(0)(lambda) following a
      power law (-)rho = rho(0) +Ar(-gamma) with a universal exponent gamma=0.46 (2) ,
      independent of lambda . The asymptotic value has the behavior rho(0)
      approximately |1-lambda|(beta) , where beta=0.26 (1) . The characteristic
      crossover length that determines the transition from DLA- to BA-like scaling
      regimes is given by xi approximately |1-lambda|(-nu) , where nu=0.61 (1) , while
      the cluster mass at the crossover follows a power law M(xi) approximately |1
      lambda(-alpha) , where alpha=0.97 (2) . We deduce the scaling relations
      beta=nugamma and beta=2nu-alpha between these exponents.

PMID- 16089531
TI  - Wall-fluid and liquid-gas interfaces of model colloid-polymer mixtures by
      simulation and theory.
AB  - We perform a study of the interfacial properties of a model suspension of hard
      sphere colloids with diameter sigma(c) and nonadsorbing ideal polymer coils with
      diameter sigma(p) . For the mixture in contact with a planar hard wall, we obtain
      from simulations the wall-fluid interfacial free energy, gamma(wf) , for size
      ratios q =sigma(p)/sigma(c) =0.6 and 1, using thermodynamic integration, and
      study the (excess) adsorption of colloids, Gamma(c) , and of polymers, Gamma(p) ,
      at the hard wall. The interfacial tension of the free liquid-gas interface,
      gamma(lg) , is obtained following three different routes in simulations: (i) from
      studying the system size dependence of the interfacial width according to the
      predictions of capillary wave theory, (ii) from the probability distribution of
      the colloid density at coexistence in the grand canonical ensemble, and (iii) for
      state points where the colloidal liquid wets the wall completely, from Young's
      equation relating gamma(lg) to the difference of wall-liquid and wall-gas
      interfacial tensions, gamma(wl)-gamma(wg) . In addition, we calculate gamma(wf)
      ,Gamma(c) , and Gamma(p) using density functional theory and a scaled particle
      theory based on free volume theory. Good agreement is found between the
      simulation results and those from density functional theory, while the results
      from scaled particle theory quantitatively deviate but reproduce some essential
      features. Simulation results for gamma(lg) obtained from the three different
      routes are all in good agreement. Density functional theory predicts gamma(lg)
      with good accuracy for high polymer reservoir packing fractions, but yields
      deviations from the simulation results close to the critical point.

PMID- 16089532
TI  - Triple-line decoration and line tension in simple three-dimensional foam
      clusters.
AB  - We show that if the triple line around a three-dimensional double bubble or lens
      bubble is decorated with another bubble or with a Plateau border, then the film
      prolongations into the decoration no longer meet at 2pi/3. These deviations can
      be accounted for in terms of a line tension that equals half the excess surface
      energy associated with the decoration.

PMID- 16089533
TI  - Structure formation in a binary monolayer of dipolar particles.
AB  - We propose an experimental technique for an easy to control realization of a
      binary dipolar monolayer where the two components have oppositely oriented dipole
      moments constrained perpendicular to the plane of motion without the application
      of an external field. The experimental setup ensures that hydrodynamic effects do
      not play a crucial role in the structure formation, the particles move
      deterministically due to the dipole-dipole interaction. At low concentrations,
      cluster-cluster aggregation occurs with chainlike morphologies, while at high
      concentration the particles self-assemble into various types of binary crystal
      lattices, in good agreement with the theoretical predictions. The structures
      formed by the particles are found to be sensitive to external perturbations due
      to the central interparticle forces, however, static friction arising at the
      contact surface of particles can increase the stability compared to systems with
      only viscous friction.

PMID- 16089534
TI  - Simulation and theory of fluid demixing and interfacial tension of mixtures of
      colloids and nonideal polymers.
AB  - An extension of the Asakura-Oosawa-Vrij model of hard sphere colloids and
      nonadsorbing polymers is studied with grand canonical Monte Carlo simulations and
      density functional theory. Polymer nonideality is taken into account through a
      repulsive step-function pair potential between polymers. Simulation results
      validate previous theoretical findings for the shift of the bulk fluid demixing
      binodal upon increasing strength of polymer-polymer repulsion, indicating
      suppression of phase separation. For increasing strength of the polymer-polymer
      repulsion, simulation and theory consistently predict the interfacial tension of
      the free interface between the colloidal liquid and the colloidal gas phase to
      decrease significantly for fixed colloid density difference in the coexisting
      phases, and to increase for fixed polymer reservoir packing fraction.

PMID- 16089535
TI  - Anisotropic diffusion in nematic liquid crystals and in ferrofluids.
AB  - A unified, mean-field kinetic theory approach to the anisotropic translational
      diffusion observed in liquid crystals and in ferrofluids is proposed. In the
      dilute regime, unified expressions for the parallel as well as for the
      perpendicular diffusion coefficient in terms of orientational order parameters
      are found that apply for liquid crystals as well as for ferrofluids. This result
      explains the common origin of the anisotropic diffusion found in liquid crystals
      and in ferrofluids. Differences between the two liquids appear in the semi-dilute
      regime, where the diffusion coefficients depend on the specific interaction
      potentials. Explicit expressions for the diffusion coefficients are worked out
      also in this regime within a mean-field approximation. Comparisons with previous
      theoretical and experimental results are performed, showing satisfactory
      agreement to the present results.

PMID- 16089536
TI  - Yang-Yang anomalies and coexistence diameters: simulation of asymmetric fluids.
AB  - A general method for estimating the Yang-Yang ratio, R(mu) , of a model fluid via
      Monte Carlo simulations is presented on the basis of data for a hard-core square
      well (HCSW) fluid and the restricted primitive model (RPM) electrolyte. The
      isothermal minima of Q(L)(triple bond)<m(2)>2L/<m(4)>L scaling are evaluated at
      T(c) in an LxLxL box where m=rho-<rho>L is the density fluctuation. The
      "complete" finite-size scaling theory for the Q(+/-)(min) (T(c);L) incorporates
      pressure mixing in the scaling fields, thereby allowing for a Yang-Yang anomaly.
      It yields a dominant term in the asymmetry, Q(+)(min)-Q(-)(min) , varying as L(
      beta/nu) with an amplitude proportional to the crucial pressure-mixing
      coefficient, j(2) . The reliably known critical order-parameter distribution for
      (d=3) Ising systems then enables one to estimate j(2) , thereby yielding R(mu) ,
      from the Q minima together with information on the nonuniversal amplitudes for
      the order parameter and the susceptibility. The detailed analysis needed to
      estimate j(2) for an HCSW fluid and the RPM is presented. Furthermore, the Q
      minima below T(c) can also provide the coexistence-curve diameters, rho(diam) (T)
      (triple bond)1/2 (rho(+) + rho(-)) , very close to T(c) for both models: here rho
      +/-(T) are the densities of the coexisting liquid and gas phases. The recently
      developed recursive scaling algorithm for Deltarho(infinity) (T) (triple
      bond)rho(+)-rho(-) is adapted to investigate the corresponding universal scaling
      functions. The two extremal forms of these scaling functions are computed with
      the aid of the exactly soluble decorated lattice-gas model. The critical
      densities for the RPM and HCSW fluid found via this route are consistent with
      previous estimates obtained from the data above T(c) ; the magnitudes of the |T-
      T(c)|(2beta) and |T- T(c)|(1-alpha) corrections to rho(diam)(T) are estimated.

PMID- 16089537
TI  - Hydration of an apolar solute in a two-dimensional waterlike lattice fluid.
AB  - In a previous work, we investigated a two-dimensional lattice-fluid model,
      displaying some waterlike thermodynamic anomalies. The model, defined on a
      triangular lattice, is now extended to aqueous solutions with apolar species.
      Water molecules are of the "Mercedes Benz" type, i.e., they possess a D3
      (equilateral triangle) symmetry, with three equivalent bonding arms. Bond
      formation depends both on orientation and local density. The insertion of inert
      molecules displays typical signatures of hydrophobic hydration: large positive
      transfer free energy, large negative transfer entropy (at low temperature),
      strong temperature dependence of the transfer enthalpy and entropy, i.e., large
      (positive) transfer heat capacity. Model properties are derived by a generalized
      first order approximation on a triangle cluster.

PMID- 16089538
TI  - Nonlinear microstructure and rheology of semidilute colloidal suspensions of
      structureless particles.
AB  - We investigate the influence of hydrodynamic and particle-particle interactions
      on the microstructure and rheological properties of semidilute colloidal
      suspensions of structureless particles. The time evolution is described in a
      mesoscopic setting in which the correlation tensor (second moment of the pair
      correlation function) is used as the microstructural state variable. Numerical
      solutions of the governing equations are then presented as linear and nonlinear
      responses of the suspensions to simple viscometric flows.

PMID- 16089539
TI  - Side-branch growth in two-dimensional dendrites. II. Phase-field model.
AB  - The development of side-branching in solidifying dendrites in a regime of large
      values of the Peclet number is studied by means of a phase-field model. We have
      compared our numerical results with experiments of the preceding paper and we
      obtain good qualitative agreement. The growth rate of each side branch shows a
      power-law behavior from the early stages of its life. From their birth, branches
      which finally succeed in the competition process of side-branching development
      have a greater growth exponent than branches which are stopped. Coarsening of
      branches is entirely defined by their geometrical position relative to their
      dominant neighbors. The winner branches escape from the diffusive field of the
      main dendrite and become independent dendrites.

PMID- 16089540
TI  - Free fluid vesicles are not exactly spherical.
AB  - At finite temperature, vesicles perform small fluctuations around an average
      shape. In the limit of low temperature or high bending rigidity, the fluctuations
      vanish and the vesicle approaches the energetically favored configuration. In the
      absence of a volume constraint the configuration of lowest energy is a perfect
      sphere. It is often assumed that the spherical shape is also the most probable
      shape for finite temperatures. Consequently, a force would have to be applied to
      make the average shape of the vesicle anisotropic. In this article it is shown
      that these assumptions are incorrect. At finite temperature, the most probable
      shapes of a vesicle without volume constraint are prolate or oblate, where the
      probability for prolate shapes is slightly larger. For larger deviations from the
      sphere the vesicle behaves as expected. The behavior at small deformations that
      is found for vesicles without volume constraint as well as in the presence of a
      finite osmotic pressure is basically an entropic effect. It already occurs in a
      three-dimensional crossed dumbbells model system. In two dimensions the same
      model favors the isotropic state.

PMID- 16089541
TI  - Instability and droplet formation in evaporating thin films of a binary solution.
AB  - We consider an instability phenomenon in a bilayer structure resulting from phase
      separation in a thin film of mixed solutions located on a water surface. The top
      layer consists of a hexane/hexadecylamine solution with thickness d(2) , the
      lower one of an amyl acetate/cellulose solution with thickness d(1) . During
      evaporation of the solvents from both layers, their thickness, surface tension,
      and viscosity change continuously with time. The thickness d(2) decreases
      significantly faster than the thickness d(1) , because the evaporation rate of
      hexane is much larger than that of amyl acetate. Eventually, the top layer
      decomposes into droplets when its thickness d(2) was only a few nm, while the
      thickness d(1) was still some 100 nm . In addition to the experiments, we present
      calculations based on energetic arguments which are in good agreement with
      experimentally determined geometrical parameters of the droplet pattern, such as
      droplet diameter, droplet height, interdroplet distance, and number of droplets
      per unit area.

PMID- 16089542
TI  - Molecular dynamics simulation of paracetamol molecules ordering around glycogen.
AB  - By the use of classical atomistic molecular dynamics simulations, we demonstrate
      that paracetamol molecules exist in a highly ordered phase in the presence of a
      glycogen substrate at 317 K whereas the paracetamol fluid exists in an isotropic
      phase in the absence of the glycogen substrate at the same temperature. This
      result further validates the studies made on polysaccharide regarding its
      abilities to promote nucleation of paracetamol via liquid preordering. As little
      is known regarding liquid ordering induced by a polymeric substrate, we seek to
      explore the ordering mechanism from an energy perspective. This is accomplished
      using conformation mappings. Our analysis shows that the conformation space
      accessible to the paracetamol molecule at 317 K in the vicinity of glycogen is
      smaller than the one in the absence of glycogen. An investigation on the
      orientation of the dipole moments of the glycogen monomers and paracetamol
      molecules were carried out as well. From the investigations, we show that dipolar
      interactions play an important role in the ordering process. These studies bear
      significance to the understanding of the ordering process as well as the
      promotion and effective control of the nucleation rate.

PMID- 16089543
TI  - Liquid-vapor interface, cavitation, and the phase diagram of water.
AB  - The study of the liquid-vapor interface and of the cavitation phenomenon in water
      can give deeper insight in its metastable phase diagram. We show how two
      different equations of state proposed for water, combined with the van der Waals
      Cahn-Hilliard theory of a nonuniform system, lead to qualitatively different
      predictions. In particular, the thickness of the liquid-vapor interface is found
      either to increase with temperature or to exhibit a minimum. Comparison with
      available data favors the monotonic behavior and suggests directions for future
      measurements.

PMID- 16089544
TI  - Continuum model for mesh crystallization.
AB  - The front propagation of a single crystallizing domain has been well studied for
      more than a century. In many important crystallization processes, however,
      multiple domains grow simultaneously, resulting in a multicrystalline, meshlike
      aggregate. This is the typical case for organic compounds, including polymers and
      alkanes. We have studied such growth in the case of a normal alkane precipitating
      from solution in the presence of kinetic inhibitors--additives which, when
      present in trace amounts, have a dramatic effect on growth kinetics and
      morphology. In this case, we observe a distinct banded growth with a typical
      length scale of 300 microm superimposed on the finer mesh structure. We present a
      simple continuum model that demonstrates the essential behavior of this growth.

PMID- 16089545
TI  - Telephone-cord instabilities in thin smectic capillaries.
AB  - Telephone-cord patterns have been recently observed in smectic liquid-crystal
      capillaries. We analyze the effects that may induce them. As long as the
      capillary keeps its linear shape, we show that a nonzero chiral cholesteric pitch
      favors the Sm-A*-Sm-C* transition. However, neither the cholesteric pitch nor the
      presence of an intrinsic bending stress is able to give rise to a curved
      capillary shape. The key ingredient for the telephone-cord instability is
      spontaneous polarization. The free-energy minimizer of a spontaneously polarized
      Sm-A* phase is attained on a planar capillary, characterized by a nonzero
      curvature. More interestingly, in the Sm-C* phase the combined effect of the
      molecular tilt and the spontaneous polarization pushes towards a helicoidal
      capillary shape, with nonzero curvature and torsion.

PMID- 16089546
TI  - Scattering of light in cholesteric liquid crystals with large pitch.
AB  - We consider the problem of light scattering in a slab of cholesteric liquid
      crystal with the pitch which significantly exceeds the wavelength of light. The
      electromagnetic wave propagation and the Green's function are investigated for
      this medium basing on geometric optics approximation. The correlation function of
      the director fluctuations is calculated with the aid of the vector analog of the
      WKB approximation. A general approach to treatment of single light scattering in
      a stratified medium with smoothly varying properties based on the Kirchhoff
      method is developed. Angular and polarization dependencies of the single light
      scattering intensity as well as extinction of the mean field are analyzed.
      Unusual dependence of the light scattering intensity on the size of the system is
      found.

PMID- 16089547
TI  - Demonstration of the antiferroelectric aspect of the helical superstructures in
      Sm-C*, Sm-C*alpha, and Sm-C*a liquid crystals.
AB  - We show that the helical superstructure in chiral smectic-C-type liquid crystal
      phases can, if the pitch is short enough, give rise to the tristate switching
      characteristic of antiferroelectrics even if the local commensurate order is
      synpolar as in the ordinary Sm-C* phase. Since the field-induced helix unwinding
      exhibits a distinct threshold, in contrast to mere helix distortion, two
      unwinding / rewinding peaks per half cycle of an applied triangular wave voltage
      can be seen in the current response. By considering this antiferroelectric aspect
      of the helical modulation we give a simple explanation of why the ultrashort
      pitch Sm-C*alpha phase exhibits antiferroelectric switching although its
      dielectric spectroscopy response is qualitatively identical to that of the
      synpolar Sm-C* phase. Using data from the compound MHPOCBC we show that the Sm
      C*alpha dielectric response is well described by continuum theory. We also
      demonstrate that, if the pitch is very short as in MHPOCBC, helix
      unwinding/rewinding leave characteristic traces in the electrooptic response even
      in the commensurately antiferroelectric (antipolar) Sm-C*(a) phase,
      distinguishable from the switching between the antipolar and synpolar states of
      this phase.

PMID- 16089548
TI  - Atomic force microscope study of presmectic modulation in the nematic and
      isotropic phases of the liquid crystal octylcyanobiphenyl using piezoresistive
      force detection.
AB  - Using a temperature controlled atomic force microscope (AFM), we have studied
      surface induced pre-smectic order in the nematic and isotropic phases of 4-cyano-
      4'-n -octylbiphenyl. A modified AFM head with piezoresitive cantilevers has been
      used to measure the structural force between a flat BK7 glass plate and a 10
      microm glass sphere, both being treated to induce homeotropic alignment of the
      confined liquid crystal layer in between. We have observed surface-induced
      presmectic force not only in the isotropic, but also in the nematic phase. We
      have measured the temperature dependencies of the presmectic force, the smectic
      correlation length xi and the smectic order parameter psi at the surface. The
      correlation length xi(T) shows a power-law temperature dependence with a critical
      exponent of nu=0.67 +/- 0.03 and the bare correlation length of xi(0) = (0.39 +/-
      0.08) nm, in good agreement with x-ray data. The smectic density at the surface
      is psi(2)(S) =0.4 in the nematic phase and decreases in the isotropic phase.

PMID- 16089549
TI  - Trans-cis isomerization and the blue phases.
AB  - A new class of photoactive chiral liquid crystals based on a photoactive nematic
      host material and a photoinactive chiral dopant was utilized to investigate the
      behavior of the blues phases when trans-cis isomerization is induced. While the
      general behavior follows what has been observed in the cholesteric phase, the
      sensitivity of the blue phases to external parameters causes different behavior
      when these systems are exposed to UV radiation. The results for four different
      mixtures are reported and include (1) modulation of the blue phase selective
      reflection wavelength with low levels of UV and visible light, (2) conversion of
      one blue phase to another upon exposure to UV light, and (3) induction of blue
      phases due to UV irradiation when no blue phases are stable beforehand. It is
      also noted that the supercooled blue phase behaves differently from the other
      blue phases. All of these results can be understood qualitatively from the ratio
      of non-nematogenic cis isomers to nematogenic trans isomers and chiral molecules.

PMID- 16089550
TI  - Viscosity peaks at the cholesteric-isotropic phase transitions.
AB  - In this work, the effective viscosity of the cholesteryl myristate and
      cholesteryl nonanoate liquid crystals is studied as a function of temperature at
      the region of their cholesteric-to-isotropic phase transition, where blue phases
      are found. Using a change of scale it is shown that the viscosity peaks that
      characterize these phase transitions are shape invariant, which suggests that
      large-scale fluctuations on the two-point correlation function give an important
      contribution to the observed viscosity. The consequences of this fact are
      investigated and, from the experimental data, the critical exponents associated
      with the diverging two-point correlation function are calculated. The results
      found for both compounds are essentially the same, being also in good agreement
      with the known values of the corresponding critical exponents of nematic
      isotropic phase transition.

PMID- 16089551
TI  - Planar-fingerprint transition in a thermoreversible liquid crystalline gel.
AB  - A thermoreversible (physical) gel consisting of a nematic liquid crystal mixed
      with a small quantity of a chiral organogelator is investigated in the planar
      configuration. The response of the system to an external electric field reveals
      multistability within a small hysteresis. The relaxation of the liquid crystal
      under this field is characterized by two different time scales: a fast one that
      is connected to the tilt of the director field, and a slow one that describes the
      reorientation of the chiral structure. In the first case, the relaxation is
      nonexponential and can be described by a Kohlrausch-Williams-Watts law with a
      stretching parameter of 0.5.

PMID- 16089552
TI  - Surface anchoring and dynamics of jump-wise director reorientations in planar
      cholesteric layers.
AB  - A theoretical investigation is made into the dynamics of pitch jumps in
      cholesteric liquid-crystal layers having finite strength surface-anchoring
      conditions. A presentation is given of general formulations which connect the
      dynamics of pitch jumps with the key material parameters such as the viscosity,
      the specific form of the anchoring potential, and the dimensionless parameter
      S(d)=K(22)/Wd , where K22 is the elastic modulus, W is the depth of the anchoring
      potential, and d is the layer thickness. To illustrate the dependence of the
      pitch jump dynamics upon the shape and strength of the anchoring potential, we
      investigate two sets of different model surface-anchoring potentials for a jump
      mechanism that is connected with the slipping of the director at a surface over
      the barrier of the anchoring potential. Two types of "narrow" well potentials
      that are natural extensions of the more familiar "wide" potentials are
      considered: one type is based upon the well-known Rapini-Papoular potential and
      the other upon the B potential, introduced in Belyakov, Stewart, and Osipov, JETP
      99, 73 (2004). Calculations for the unwinding (winding) of the helix in the
      process of the jump were performed to investigate the case of infinitely strong
      anchoring on one surface and finite anchoring on the other, which is important in
      applications. The results show that an experimental investigation of the dynamics
      of the pitch jumps will allow one to distinguish different shapes of the finite
      strength anchoring potential, and will, in particular, provide a means for
      determining whether or not the well-known Rapini-Papoular anchoring potential is
      the best suited potential relevant to the dynamics of pitch jumps in cholesteric
      layers with finite surface-anchoring strength.

PMID- 16089553
TI  - Influence of nanosized confinements on 4-n-decyl-4'-cyanobiphenyl (10CB): a
      broadband dielectric study.
AB  - Real (epsilon') and imaginary (epsilon") parts of the complex dielectric
      permittivity (epsilon*) of the liquid crystal (LC) 4-n-decyl-4'-cyanobiphenyl
      (10CB) embedded in Anopore membranes and Vycor porous glass, as well as dispersed
      with hydrophilic aerosils, have been studied by means of broadband dielectric
      spectroscopy in the frequency range from 10(-2) Hz to 1 GHz . In bulk 10CB, which
      has a direct transition from an isotropic to a smectic- A phase, there exists one
      main relaxation process for the parallel orientation of the director with respect
      to the probing field and a faster one for the perpendicular orientation. All
      molecular relaxation processes in 10CB are of Debye type and have Arrhenius like
      temperature dependence. For 10CB embedded in untreated and surface treated
      cylindrical pores of Anopore membranes the dielectric spectra are similar to the
      bulk with the exception that both the rotation around the short axis and the
      libration motion are faster in the pores. In the case of 10CB dispersed with two
      different concentrations of hydrophilic aerosils an emergence of a slow
      relaxation process, which is stronger for the higher concentration, is
      additionally observed along with the bulklike processes. The slow process in the
      LC-hydrophilic aerosil system is attributed to the relaxation of the molecules
      that are homeotropically aligned close to the surfaces of the aerosil particles.
      This process also has an Arrhenius type of temperature dependence. For 10CB
      embedded in narrow channels of Vycor porous glass three relaxation processes are
      observed. Two of these processes are bulklike and are due to the librational
      motion of molecules and the rotation of molecules around their short axes. The
      slowest process seems to be a surface process, similar in origin to that observed
      for 10CB dispersed with hydrophilic aerosils, and is prominent amongst all. The
      material in the Vycor porous glass could be supercooled by at least 185 degrees
      below bulk crystallization temperature. The slow process has a Vogel-Fulcher
      Tamman (VFT) type of temperature dependence typical for glass formers in this
      wide temperature range. In addition, the bulklike processes are found to be
      strongly modified and also have a VFT like temperature dependence from
      measurements done in a wide temperature range. This behavior is in contrast to
      other reports of glassy behavior in confined LC, where the glassy behavior as
      concluded from a slow relaxation process observed in a narrow temperature range.

PMID- 16089554
TI  - Smectic phase in a system of hard ellipsoids with isotropic attractive
      interactions.
AB  - The smectic phase is studied for a thermotropic fluid model consisting of aligned
      hard ellipsoids with superimposed square-well attractive interactions of variable
      range. The system is analyzed using a density functional theory in which the hard
      core contributions to the free-energy functional are treated within a nonlocal
      weighted density approximation and the attractive contributions are considered at
      a mean-field level. In the absence of attractions the model reduces, under
      appropriate scaling, to a fluid of hard spheres and therefore does not exhibit
      smectic ordering. It is shown that above a certain value of the square-well
      range, smectic ordering is stable relative to the nematic state at densities well
      inside the fluid region. The nematic-smectic-A transition is found to be
      continuous at high temperatures and first order at low temperatures, these two
      regimes being separated by a tricritical point at an intermediate temperature.
      These predictions have been confirmed by computer simulation of the model fluid.
      The results highlight that smectic ordering can be stabilized by coupling
      anisotropic short-range repulsions with the isotropic contribution of the soft
      attractive interactions. By increasing the pressure, the range of stability of
      the smectic phase is seen to decrease. At sufficiently high pressure, the smectic
      phase is suppressed, and the solid phase dominates. Our calculations show that
      smectic ordering is no longer stable if the range of the attractions is made too
      long ranged.

PMID- 16089555
TI  - Influence of the backflow effect on the orientational dynamics induced by light
      in nematics.
AB  - We investigate the dynamical phenomena induced by a circularly polarized plane
      wave incident perpendicularly on a homeotropically aligned nematic layer. We
      study theoretically the influence of the velocity field (backflow effect) on the
      bifurcation scenario. Whereas backflow leads to substantial quantitative changes
      of secondary bifurcation thresholds, the overall bifurcation scenario remains
      unchanged. In the regime of uniform precession of the director with large
      reorientation, an unanticipated spatial oscillation of the flow field across the
      layer is found. Quantitative comparison with experimental large-aspect ratio
      systems is now possible.

PMID- 16089556
TI  - Correlation length and chirality of the fluctuations in the isotropic phase of
      nematic and cholesteric liquid crystals.
AB  - Light-scattering measurements of the correlation length in the isotropic phase of
      a nematic liquid crystal reveal a temperature dependence following Landau-de
      Gennes theory for the isotropic phase with a bare correlation length smaller than
      has been measured in other liquid crystals. Similar measurements in a cholesteric
      liquid crystal demonstrate that the correlation length in the isotropic phase is
      larger than typically found in nematics and that the chirality of the
      fluctuations in the isotropic phase is slightly higher than the chirality of the
      cholesteric phase. Landau-de Gennes theory of the cholesteric phase describes the
      chirality in the cholesteric phase well but predicts that the chirality in the
      isotropic phase is temperature independent, which is not consistent with the
      data. There is a discontinuity in the chirality at the cholesteric-isotropic
      transition of about 15%, which is less than the predictions of Landau-de Gennes
      theory but more than the typical specific volume discontinuity at transitions to
      the isotropic phase. Except for a mismatch in the discontinuities at the
      transition, the chirality data resemble the temperature behavior of variables
      just below a critical point, in spite of the fact that this system is far from a
      critical point.

PMID- 16089557
TI  - Electrically driven deformations of nematic gels.
AB  - The electrically driven deformations of side chain nematic networks swollen by
      nematic solvents (nematic gels) have been investigated. The strains of freely
      suspended gels between electrodes were measured as a function of field strength
      (E) . The deformation of the gels composed of a network and solvent with
      identical signs of dielectric anisotropy (Delta epsilon) is dominated by the
      electrically induced alignment of the nematogens. As a result, the stretching
      direction is variable according to the sign of Delta epsilon: The gel with
      positive or negative Delta epsilon is elongated parallel or normal to the field
      axis, respectively. The maximum strain among the samples examined is as large as
      20% at E approximately equal to 0.5 MV/m. The gels composed of a network and
      solvent with opposite signs of Delta epsilon are compressed along the field axis
      since the electrostrictive effect becomes dominant because of a large reduction
      in the mesogen alignment effect due to the discord in the director directions of
      the constituent nematogens. The gels in the isotropic phase show compressive
      strains along the field direction in proportion to E2 purely originating from
      electrostriction, independently of the sign of Delta epsilon. The nematic gels
      are quickly deformed within a second upon field application, while the shape
      recovery after field removal requires a finite time on the order of 10(3) s,
      which reflects the structural relaxation in the polydomain texture from the
      oriented to the random state. The influences of elastic modulus as well as
      network nematicity on the electrical deformation are also examined.

PMID- 16089558
TI  - Minimal coupling model of the biaxial nematic phase.
AB  - A minimal coupling model exhibiting isotropic, uniaxial, and biaxial nematic
      phases is analyzed in detail and its relation to existing models known in the
      literature is clarified. Its intrinsic symmetry properties are exploited to
      restrict the relevant ranges of coupling constants. Further on, properties of the
      model are thoroughly investigated by means of bifurcation theory as proposed by
      Kayser and Raveche [Phys. Rev. A 17, 2067 (1978)] and Mulder [Phys. Rev. A 39,
      360 (1989)]. As a first step toward this goal, the bifurcation theory is applied
      to a general formulation of density functional theory in terms of direct
      correlation functions. On a general formal level, the theory is then analyzed to
      show that the bifurcation points from the reference, high-symmetry equilibrium
      phase to a low-symmetry structure depend only on the properties of the one
      particle distribution function and the direct pair correlation function of the
      reference phase. The character of the bifurcation (whether spinodal, critical,
      tricritical, isolated Landau point, etc.) depends, in addition, on a few higher
      order direct correlation functions. Explicit analytical results are derived for
      the case when only the leading L=2 terms of the potential (mean-field analysis)
      or of the direct pair correlation function expansion in the symmetry-adapted
      basis are retained. Formulas are compared with the numerical calculations for the
      mean-field, momentum L=2 potential model, in which case they are exact. In
      particular, bifurcations from the isotropic and uniaxial nematic to the biaxial
      nematic phases are discussed. The possibility of the recently reported nematic
      uniaxial-nematic biaxial tricritical point [A. M. Sonnet, E. G. Virga, and G. E.
      Durand, Phys. Rev. E 67, 061701 (2003)] is analyzed as well.

PMID- 16089559
TI  - High frequency hysteresis-free switching in thin layers of smectic-C*
      ferroelectric liquid crystals.
AB  - The insulating layers used for the alignment of ferroelectric liquid crystals
      (FLC) in electro-optical cells usually have non-negligible thickness and their
      capacitance determines the type of the director switching caused by a triangular
      form external voltage U(tr) . With decreasing frequency of U(tr) , the hysteresis
      in a switching direction changes from the normal to the abnormal one at a
      characteristic hysteresis inversion frequency f(i) . In the vicinity of f(i) ,
      the electro-optical response is thresholdless and the optical transmission
      manifests the V -shape field dependence. The V -shape regime is very interesting
      for certain applications, in particular to microdisplays due to a possibility of
      the gray scale realization. However, f(i) has to be enhanced from the usually
      observed frequency of a few Hz up to the range of hundreds of Hz. To this effect,
      a special FLC material has been designed and its basic properties (tilt angle,
      spontaneous polarization, rotational viscosity, and electric conductivity) have
      been measured over the entire range of the smectic-C* phase. Upon variation of
      cell parameters (thickness of both the FLC and alignment layers), temperature,
      and external voltage, the frequency of the V -shape effect as high as 150-1000 Hz
      (in the temperature range 30-75 degrees C) has been found experimentally. The
      operating voltage remains lower than 8 V. A quantitative interpretation of these
      results has been done using the modeling procedure developed earlier [S.P. Palto,
      Cryst. Rep. 48, 124 (2003)]. The modeling has been performed with the
      experimental values of the FLC material and the cell parameters and has shown
      very good agreement with experiment. The key point of this approach is
      consideration of the internal voltage on the FLC layer, the sign, amplitude, and
      form of which differ from U(tr) . The results of the modeling allow further
      improvement of the performance of electro-optical FLC cells for high frequency V
      shape effect.

PMID- 16089560
TI  - Interfacial tension of the isotropic-nematic interface in suspensions of soft
      spherocylinders.
AB  - The isotropic to nematic transition in a system of soft spherocylinders is
      studied by means of grand canonical Monte Carlo simulations. The probability
      distribution of the particle density is used to determine the coexistence
      densities of the isotropic and the nematic phases. The distributions are also
      used to compute the interfacial tension of the isotropic-nematic interface,
      including an analysis of finite size effects. Our results confirm that the
      Onsager limit is not recovered until for very large elongation, exceeding at
      least L/D=40 , with L the spherocylinder length and D the diameter. For smaller
      elongation, we find that the interfacial tension increases with increasing L/D ,
      in agreement with theoretical predictions.

PMID- 16089561
TI  - Self-consistent field theory of multiply branched block copolymer melts.
AB  - We present a numerical algorithm to evaluate the self-consistent field theory for
      melts composed of block copolymers with multiply branched architecture. We
      present results for the case of branched copolymers with doubly functional groups
      for multiple-branching generations. We discuss the stability of the cubic phase
      of spherical micelles, the A15 phase, as a consequence of the tendency of the AB
      interfaces to conform to the polyhedral environment of the Voronoi cell of the
      micelle lattice.

PMID- 16089562
TI  - Intermolecular adhesion in conducting polymers.
AB  - We analyze the interaction of two conducting, charged polymer chains in solution
      using a minimal model for their electronic degrees of freedom. We show that a
      crossing of the two chains in which the polymers pass within angstroms of each
      other leads to a decrease of the electronic energy of the combined system that is
      significantly larger than the thermal energy and thus promotes interchain
      aggregation. We consider the competition of this attractive interaction with the
      screened electrostatic repulsion and thereby propose a phase diagram for such
      polymers in solution; depending on the charge density and persistence length of
      the chains, the polymers may be unbound, bound in loose, braidlike structures, or
      tightly bound in a parallel configuration.

PMID- 16089563
TI  - Orientational order transition of the striped microphase structure of a copolymer
      homopolymer mixture under oscillatory particles.
AB  - Based on the three-order-parameter model, we investigate the orientational order
      transition of striped patterns in microphase structures of diblock copolymer
      homopolymer mixtures in the presence of periodic oscillatory particles. Under
      suitable conditions, although the macrophase separation of a system is almost
      isotropic, the microphase separation of the system will be significantly
      perturbed by the oscillatory field, and composition fluctuations are suppressed
      anisotropically. The isotropy of the microphase will be broken up. By changing
      the oscillatory amplitude and frequency, we observe the orientational order
      transition of a striped microphase structure from the isotropic state to a state
      parallel to the oscillatory direction, and from the parallel state to a state
      perpendicular to the oscillatory direction. We examine, in detail, the
      microstructure and orientational order parameter as well as the domain size in
      the process of orientational order transition under the oscillatory field. We
      study also how the microphase structure changes with the composition ratio of
      homopolymers and copolymers in mixtures. The results suggest that our model
      system may provide a simple way to realize orientational order transition of soft
      materials.

PMID- 16089564
TI  - Force-induced triple point for interacting polymers.
AB  - We show the existence of a force induced triple point in an interacting polymer
      problem that allows two zero-force thermal phase transitions. The phase diagrams
      for two different models of mutually attracting but self-avoiding polymers are
      presented. One of these models has an intermediate phase and it shows a triple
      point. A general phase diagram with multicritical points in an extended parameter
      space is also discussed.

PMID- 16089565
TI  - Nonexponential relaxation and hierarchically constrained dynamics in a protein.
AB  - A scaling analysis within a model of hierarchically constrained dynamics is shown
      to reproduce the main features of nonexponential relaxation observed in kinetic
      studies of carbonmonoxymyoglobin.

PMID- 16089567
TI  - Translocation of double-strand DNA through a silicon oxide nanopore.
AB  - We report double-strand DNA translocation experiments using silicon oxide
      nanopores with a diameter of about 10 nm . By monitoring the conductance of a
      voltage-biased pore, we detect molecules with a length ranging from 6557 to 48
      500 base pairs. We find that the molecules can pass the pore both in a straight
      linear fashion and in a folded state. Experiments on circular DNA further support
      this picture. We sort the molecular events according to their folding state and
      estimate the folding position. As a proof-of-principle experiment, we show that a
      nanopore can be used to distinguish the lengths of DNA fragments present in a
      mixture. These experiments pave the way for quantitative analytical techniques
      with solid-state nanopores.

PMID- 16089566
TI  - Mesoscopic modeling for nucleic acid chain dynamics.
AB  - To gain a deeper insight into cellular processes such as transcription and
      translation, one needs to uncover the mechanisms controlling the configurational
      changes of nucleic acids. As a step toward this aim, we present here a mesoscopic
      level computational model that provides a new window into nucleic acid dynamics.
      We model a single-stranded nucleic as a polymer chain whose monomers are the
      nucleosides. Each monomer comprises a bead representing the sugar molecule and a
      pin representing the base. The bead-pin complex can rotate about the backbone of
      the chain. We consider pairwise stacking and hydrogen-bonding interactions. We
      use a modified Monte Carlo dynamics that splits the dynamics into translational
      bead motion and rotational pin motion. By performing a number of tests, we first
      show that our model is physically sound. We then focus on a study of the kinetics
      of a DNA hairpin--a single-stranded molecule comprising two complementary
      segments joined by a noncomplementary loop--studied experimentally. We find that
      results from our simulations agree with experimental observations, demonstrating
      that our model is a suitable tool for the investigation of the hybridization of
      single strands.

PMID- 16089568
TI  - Noise-induced transition from translational to rotational motion of swarms.
AB  - We consider a model of active Brownian agents interacting via a harmonic
      attractive potential in a two-dimensional system in the presence of noise. By
      numerical simulations, we show that this model possesses a noise-induced
      transition characterized by the breakdown of translational motion and the onset
      of swarm rotation as the noise intensity is increased. Statistical properties of
      swarm dynamics in the weak noise limit are further analytically investigated.

PMID- 16089569
TI  - Effects of kinks on DNA elasticity.
AB  - We study the elastic response of a wormlike polymer chain with reversible
      kinklike structural defects. This is a generic model for (a) the double-stranded
      DNA with sharp bends induced by binding of certain proteins, and (b) effects of
      trans-gauche rotations in the backbone of the single-stranded DNA. The problem is
      solved both analytically and numerically by generalizing the well-known analogy
      to the quantum rotator. In the small stretching force regime, we find that the
      persistence length is renormalized due to the presence of the kinks. In the
      opposite regime, the response to the strong stretching is determined solely by
      the bare persistence length with exponential corrections due to the "ideal gas of
      kinks." This high-force behavior changes significantly in the limit of high
      bending rigidity of the chain. In that case, the leading corrections to the
      mechanical response are likely to be due to the formation of multikink
      structures, such as kink pairs.

PMID- 16089570
TI  - Nonequilibrium patterns and shape fluctuations in reactive membranes.
AB  - A simple kinetic model of a two-component deformable and reactive bilayer is
      presented. The two differently shaped components are interconverted by a
      nonequilibrium reaction, and a phenomenological coupling between local
      composition and curvature is proposed. When the two components are not miscible,
      linear stability analysis predicts, and numerical simulations show, the formation
      of stationary nonequilibrium composition/curvature patterns whose typical size is
      determined by the reactive process. For miscible components, a linearization of
      the dynamic equations is performed in order to evaluate the correlation function
      for shape fluctuations from which the behavior of these systems in micropipet
      aspiration experiments can be predicted.

PMID- 16089571
TI  - Stochastic discrete event simulation of germinal center reactions.
AB  - We introduce a generic reaction-diffusion model for germinal center reactions and
      perform numerical simulations within a stochastic discrete event approach. In
      contrast to the frequently used deterministic continuum approach, each single
      reaction event is monitored in space and time in order to simulate the correct
      time evolution of this complex biological system. Germinal centers play an
      important role in the immune system by performing a reaction that aims at
      improving the affinity between antibodies and antigens. Our model captures
      experimentally observed features of this reaction, such as the development of the
      remarkable germinal center morphology and the maturation of antibody-antigen
      affinity in the course of time. We model affinity maturation within a simple
      affinity class picture and study it as a function of the distance between the
      initial antibody-antigen affinity and the highest possible affinity. The model
      reveals that this mutation distance may be responsible for the experimentally
      observed all-or-none behavior of germinal centers; i.e., they generate either
      mainly output cells of high affinity or no high-affinity output cells at all.
      Furthermore, the exact simulation of the system dynamics allows us to study the
      hypothesis of cell recycling in germinal centers as a mechanism for affinity
      optimization. A comparison of three possible recycling pathways indicates that
      affinity maturation is optimized by a recycling pathway that has previously not
      been taken into account in deterministic continuum models.

PMID- 16089572
TI  - Leading-edge vortex stability in insect wings.
AB  - An analytical study is presented to determine if the persistency of the leading
      edge vortex in an insect wing can be explained as the balance between vorticity
      generation at the leading edge and advection plus effects of vorticity stretching
      and tilting by the flow along the wing span. It is found that a spanwise flow of
      the required magnitude is produced by the simple rotation of the wing about its
      root at a constant angle of attack (no supination or pronation), and that the
      regions where this equilibrium exists in stable form are well localized,
      independent of the rotation velocity, almost independent of the position along
      the wing, and weakly dependent on the angle of attack, for angles below
      approximately equal to 70 degrees. In contrast, extended regions of vorticity are
      expected for angles of attack above approximately equal to 75 degrees.

PMID- 16089573
TI  - Multiple weak hits confuse complex systems: a transcriptional regulatory network
      as an example.
AB  - Robust systems, like the molecular networks of living cells, are often resistant
      to single hits such as those caused by high-specificity drugs. Here we show that
      partial weakening of the Escherichia coli and Saccharomyces cerevisiae
      transcriptional regulatory networks at a small number (3-5) of selected nodes can
      have a greater impact than the complete elimination of a single selected node. In
      both cases, the targeted nodes have the greatest possible impact; still, the
      results suggest that in some cases broader specificity compounds or multitarget
      drug therapies may be more effective than individual high-affinity, high
      specificity ones. Multiple but partial attacks mimic well a number of in vivo
      scenarios and may be useful in the efficient modification of other complex
      systems.

PMID- 16089574
TI  - Multicellular tumor spheroid in an off-lattice Voronoi-Delaunay cell model.
AB  - We study multicellular tumor spheroids by introducing a new three-dimensional
      agent-based Voronoi-Delaunay hybrid model. In this model, the cell shape varies
      from spherical in thin solution to convex polyhedral in dense tissues. The next
      neighbors of the cells are provided by a weighted Delaunay triangulation with on
      average linear computational complexity. The cellular interactions include direct
      elastic forces and cell-cell as well as cell-matrix adhesion. The spatiotemporal
      distribution of two nutrients--oxygen and glucose--is described by reaction
      diffusion equations. Viable cells consume the nutrients, which are converted into
      biomass by increasing the cell size during the G1 phase. We test hypotheses on
      the functional dependence of the uptake rates and use computer simulations to
      find suitable mechanisms for the induction of necrosis. This is done by comparing
      the outcome with experimental growth curves, where the best fit leads to an
      unexpected ratio of oxygen and glucose uptake rates. The model relies on physical
      quantities and can easily be generalized towards tissues involving different cell
      types. In addition, it provides many features that can be directly compared with
      the experiment.

PMID- 16089575
TI  - Dynamics of conduction blocks in a model of paced cardiac tissue.
AB  - We study numerically the dynamics of conduction blocks using a detailed
      electrophysiological model. We find that this dynamics depends critically on the
      size of the paced region. Small pacing regions lead to stationary conduction
      blocks while larger pacing regions can lead to conduction blocks that travel
      periodically towards the pacing region. We show that this size-dependence
      dynamics can lead to a novel arrhythmogenic mechanism. Furthermore, we show that
      the essential phenomena can be captured in a much simpler coupled-map model.

PMID- 16089576
TI  - Hydrodynamic stability of helical growth at low Reynolds number.
AB  - A cylindrical object growing at a low Reynolds number can spontaneously develop a
      helical shape. We have studied this phenomenon numerically, and our results may
      shed some light on the spontaneous formation of helical tails of a dense protein
      network observed in experiments on actin based motility. We also identify an
      unstable critical pitch angle which separates helices that straighten into rods
      from helices that flatten into planar curves as they grow. At the critical angle
      the pitch angle remains constant, whereas both helical diameter and pitch
      increase with the helical contour length.

PMID- 16089577
TI  - N-dimensional fractional diffusion equation and Green function approach:
      spatially dependent diffusion coefficient and external force.
AB  - We investigate an N-dimensional fractional diffusion equation with radial
      symmetry by using the Green function approach. We consider, in our analysis, the
      spatial dependence on the diffusion coefficient and the presence of an external
      force. In particular, we employ boundary conditions in a finite interval and
      after we extend it to a semi-infinite interval. We also show that a rich class of
      diffusive processes, including normal and anomalous ones, can be obtained from
      the solutions found here.

PMID- 16089578
TI  - Dipolar interactions in liquids and linear dielectric relaxation spectroscopy.
AB  - Linear dielectric relaxation studies performed on two isotropic liquids composed
      of the molecules of the same moment of inertia and a quite different polarity:
      C10H21-O-Ph-COO-Ph-CN (the dipole moment of about 5 D) and C10H21-O-Ph-OOC-Ph-CN
      (2.5 D) showed that, at given temperature, the relaxation times corresponding to
      the rotation around the short axis of the two kinds of molecules coincide to each
      other, regardless the polarity of the molecules and their abilities to accomplish
      dipolar aggregation. The studies allow one to estimate the lifetime of the
      intermolecular aggregates due to the dipolar interactions in liquids as no longer
      than 0.1 ns.

PMID- 16089579
TI  - Pretransitional critical-like behavior of dielectric permittivity in mixtures of
      mesomorphic and nonmesomorphic compounds.
AB  - Static dielectric measurements are performed in the temperature range of the
      isotropic-nematic phase transition of binary mixtures of mesomorphic n
      heptylcyanobiphenyl (7CB) and nonmesomorphic: (a) n-heptylcyanophenyl (7CP) and
      (b) carbon tetrachloride (CCl4) , the solutes of different molecular shape and
      polarity. In the whole studied range of the solutes mole fraction (x) (x(max)
      approximately equal to 0.17) , the critical-like temperature behavior of the
      permittivity in the vicinity of the transition from the isotropic phase to the
      two-phase (nematic+isotropic) region can be well described with a critical
      exponent close to 0.5, as in a pure 7CB, indicating the tricritical nature of the
      transitions. It seems to be important that the fitting-determined temperatures of
      the virtual second-order transition in the solutions, T*, i.e., the temperature
      limit of the thermodynamic stability of supercooled isotropic phase, correspond
      well to the experimentally observed low-temperature limits of the two-phase
      isotropic+nematic region.

PMID- 16089580
TI  - Elasticity and stability of a helical filament.
AB  - We derive the general shape equations in terms of Euler angles for a uniform
      elastic rod with spontaneous torsion and curvatures and subjected to external
      force and torque. Our results based on an analytic formalism show that the
      extension of a helical rod may undergo a one-step discontinuous transition with
      increasing stretching force. This agrees quantitatively with experimental
      observations for a helix in a chemically defined lipid concentrate. The larger
      the twisting rigidity, the larger the jump in the extension. The effect of torque
      on the jump is, however, dependent on the value of the spontaneous torsion. In
      contrast, increasing the spontaneous torsion encourages the continuous variation
      of the extension. An "over-collapse" behavior is observed for the rod with
      asymmetric bending rigidity, and an intrinsic asymmetric elasticity under
      twisting force is found.

PMID- 16089581
TI  - Elimination of spiral chaos by pulse entrainment in the Aliev-Panfilov model.
AB  - Pulse entrainment between two excitatory media is studied in the Aliev-Panfilov
      model. We show that a spiral chaos in the continuous excitatory medium can be
      eliminated by a grid network using the pulse entrainment. This mechanism may be
      applied to the cardiac system, where the ventricular fibrillation is interpreted
      as the spiral chaos and the Purkinje fibers act as the grid network.

PMID- 16089582
TI  - Periodicity of mass extinctions without an extraterrestrial cause.
AB  - We study a lattice model of a multispecies prey-predator system. Numerical
      results show that for a small mutation rate the model develops irregular long
      period oscillatory behavior with sizeable changes in a number of species. The
      periodicity of extinctions on Earth was suggested by Raup and Sepkoski [Proc.
      Natl. Acad. Sci. 81, 801 (1984)], but thus far is lacking a satisfactory
      explanation. Our model indicates that this might be a natural consequence of the
      ecosystem dynamics and not the result of any extraterrestrial cause.

PMID- 16089583
TI  - Comment on "Fluctuations of elastic interfaces in fluids: theory, lattice
      Boltzmann model, and simulation".
AB  - The formulas for the force exerted by the interface upon the fluids, given by
      Stelitano and Rothman [Phys. Rev. E 62, 6667 (2000)] are corrected.

PMID- 16089584
TI  - Family of solvable generalized random-matrix ensembles with unitary symmetry.
AB  - We construct a very general family of characteristic functions describing random
      matrix ensembles (RME) having a global unitary invariance, and containing an
      arbitrary, one-variable probability measure, which we characterize by a "spread
      function." Various choices of the spread function lead to a variety of possible
      generalized RMEs, which show deviations from the well-known Gaussian RME
      originally proposed by Wigner. We obtain the correlation functions of such
      generalized ensembles exactly and show examples of how particular choices of the
      spread function can describe ensembles with arbitrary eigenvalue densities as
      well as critical ensembles with multifractality.

PMID- 16089585
TI  - Branching mechanism of intergranular crack propagation in three dimensions.
AB  - We investigate the process of slow intergranular crack propagation by the finite
      element method model and show that branching is induced by partial arresting of a
      crack front owing to the geometrical randomness of grain boundaries. A possible
      scenario for the branching instability of crack propagation in a disordered
      continuous medium is also discussed.

PMID- 16089586
TI  - Congestion and decongestion in a communication network.
AB  - We study network traffic dynamics in a two-dimensional communication network with
      regular nodes and hubs. If the network experiences heavy message traffic,
      congestion occurs due to the finite capacity of the nodes. We discuss strategies
      to manipulate hub capacity and hub connections to relieve congestion and define a
      coefficient of betweenness centrality (CBC), a direct measure of network traffic,
      which is useful for identifying hubs that are most likely to cause congestion.
      The addition of assortative connections to hubs of high CBC relieves congestion
      very efficiently.

PMID- 16089587
TI  - Missing physics in stick-slip dynamics of a model for peeling of an adhesive
      tape.
AB  - It is now known that the equations of motion for the contact point during peeling
      of an adhesive tape mounted on a roll introduced earlier are singular and do not
      support dynamical jumps across the two stable branches of the peel force
      function. By including the kinetic energy of the tape in the Lagrangian, we
      derive equations of motion that support stick-slip jumps as a natural consequence
      of the inherent dynamics. In the low mass limit, these equations reproduce
      solutions obtained using a differential-algebraic algorithm introduced for the
      earlier equations. Our analysis also shows that the mass of the ribbon has a
      strong influence on the nature of the dynamics.

PMID- 16089588
TI  - Hexagons become the secondary pattern if symmetry is broken.
AB  - Pattern formation on the free surface of a magnetic fluid subjected to a magnetic
      field is investigated experimentally. By tilting the magnetic field, the symmetry
      can be broken in a controllable manner. When increasing the amplitude of the
      tilted field, the flat surface gives way to liquid ridges. A further increase
      results in a hysteretic transition to a pattern of stretched hexagons. The
      instabilities are detected by means of a linear array of magnetic Hall sensors
      and compared with theoretical predictions.

PMID- 16089589
TI  - Universal critical behavior of the synchronization transition in delayed chaotic
      systems.
AB  - We numerically investigate the critical behavior of the synchronization
      transition of two unidirectionally coupled delayed chaotic systems. We map the
      problem to a spatially extended system to show that the synchronization
      transition in delayed systems exhibits universal critical properties. We find
      that the synchronization transition is absorbing and generically belongs to the
      universality class of the bounded Kardar-Parisi-Zhang equation, as occurs in the
      case of extended systems. We also argue that directed percolation critical
      behavior may emerge for systems with strong nonlinearities.

PMID- 16089590
TI  - Effects of surface tension on immiscible Rayleigh-Taylor turbulence.
AB  - We present phenomenology describing the internal structure of a turbulent zone,
      produced as the result of the push of a heavy fluid into a light one, for the
      case of immiscible fluids. One finds that the Kolmogorov cascade is realized
      within a range that grows with time, viz., scales between the mixing zone width,
      L proportional variant t(2), and the viscous scale, eta proportional variant t(
      1/4). Surface-tension effects lead to formation of an emulsionlike state. Density
      fluctuations on scales larger than the typical drop size, l, are governed by the
      Obukhov-Corrsin cascade. If l >> eta, a wave energy cascade, related to capillary
      waves propagating along the surfaces of drops, is formed at scales below l, l
      proportional variant t(-2/5).

PMID- 16089591
TI  - Nonlinear Rayleigh-Taylor growth in converging geometry.
AB  - The early nonlinear phase of Rayleigh-Taylor growth is typically described in
      terms of the classic Layzer model in which bubbles of light fluid rise into the
      heavy fluid at a constant rate determined by the bubble radius and the
      gravitational acceleration. However, this model is strictly valid only for planar
      interfaces and hence ignores any effects that might be introduced by the
      spherically converging interfaces of interest in inertial confinement fusion and
      various astrophysical phenomena. Here, a generalization of the Layzer nonlinear
      bubble rise rate is given for a self-similar spherically converging flow of the
      type studied by Kidder. A simple formula for the bubble amplitude is found
      showing that, while the bubble initially rises with a constant velocity similar
      to the Layzer result, during the late phase of the implosion, an acceleration of
      the bubble rise rate occurs. The bubble rise rate is verified by comparison with
      numerical hydrodynamics simulations.

PMID- 16089592
TI  - Quasiplanar steep water waves.
AB  - A unique description for highly nonlinear potential water waves is suggested,
      where weak three-dimensional effects are included as small corrections to exact
      two-dimensional equations written in conformal variables. Contrary to the
      traditional approach, a small parameter in this theory is not a surface slope,
      but it is the ratio of a typical wavelength to a large transversal scale along
      the second horizontal coordinate. A first-order correction for the Hamiltonian
      functional is calculated, and the corresponding equations of motion are derived
      for steep water waves over an arbitrary nonuniform quasi-one-dimensional bottom
      profile.

PMID- 16089593
TI  - Two-dimensional sonic crystals with Helmholtz resonators.
AB  - We present a type of sonic crystal composed with an array of two-dimensional
      Helmholtz resonators, which in the long-wave regime have both a high relative
      acoustic refractive index n and at the same time, a small acoustic impedance Z
      mismatch with air for airborne sound. We analyze the n and Z of such sonic
      crystals by finite-difference time-domain simulations, and by mapping our results
      to a corresponding electromagnetic (EM) model, and we find that our Helmholtz
      resonant sonic crystal has a bigger effective magnetic permeability mu than the
      conventional rigid-cylinder sonic crystal in its EM counterpart. As a result, a
      thin convergent lens with very good focusing effect is demonstrated based on our
      crystal.

PMID- 16089594
TI  - Wave dynamics in optically modulated waveguide arrays.
AB  - A model describing wave propagation in optically modulated waveguide arrays is
      proposed. In the weakly guided regime, a two-dimensional semidiscrete nonlinear
      Schrodinger equation with the addition of a bulk diffraction term and an external
      "optical trap" is derived from first principles, i.e., Maxwell equations. When
      the nonlinearity is of the defocusing type, a family of unstaggered localized
      modes are numerically constructed. It is shown that the equation with an induced
      potential is well-posed and gives rise to localized dynamically stable nonlinear
      modes. The derived model is of the Gross-Pitaevskii type, a nonlinear Schrodinger
      equation with a linear optical potential, which also models Bose-Einstein
      condensates in a magnetic trap.

PMID- 16089595
TI  - Coherent backscattering of light by nonlinear scatterers.
AB  - We theoretically study the propagation of light in a disordered medium with
      nonlinear scatterers. We especially focus on interference effects between
      reversed multiple scattering paths, which lead to weak localization and coherent
      backscattering. We show that, in the presence of weakly nonlinear scattering,
      constructive interferences exist in general between three different scattering
      amplitudes. This effect influences the nonlinear backscattering enhancement
      factor, which may thus exceed the linear barrier two.

PMID- 16089596
TI  - Temperature dependence of the Casimir effect.
AB  - The temperature dependence of the Casimir force between a real metallic plate and
      a metallic sphere is analyzed on the basis of optical data concerning the
      dispersion relation of metals such as gold and copper. Realistic permittivities
      imply, together with basic thermodynamic considerations, that the transverse
      electric zero mode does not contribute. This results in observable differences
      from the conventional prediction, which does not take this physical requirement
      into account. The results are shown to be consistent with the third law of
      thermodynamics, as well as being not inconsistent with current experiments.
      However, the predicted temperature dependence should be detectable in future
      experiments. The inadequacies of approaches based on ad hoc assumptions, such as
      the plasma dispersion relation and the use of surface impedance without
      transverse momentum dependence, are discussed.

PMID- 16089597
TI  - Anomalous roughness with system-size-dependent local roughness exponent.
AB  - We note that in a system far from equilibrium the interface roughening may depend
      on the system size which plays the role of control parameter. To detect the size
      effect on the interface roughness, we study the scaling properties of rough
      interfaces formed in paper combustion experiments. Using paper sheets of
      different width lambda L0, we found that the turbulent flame fronts display
      anomalous multiscaling characterized by nonuniversal global roughness exponent
      alpha and the system-size-dependent spectrum of local roughness exponents zeta(q)
      (lambda) = zeta(1) (1) q(-omega) lambda(phi) <alpha, whereas the burning fronts
      possess conventional multiaffine scaling. The structure factor of turbulent flame
      fronts also exhibit unconventional scaling dependence on lambda. These results
      are expected to apply to a broad range of far from equilibrium systems, when the
      kinetic energy fluctuations exceed a certain critical value.

PMID- 16089598
TI  - Subgraph centrality in complex networks.
AB  - We introduce a new centrality measure that characterizes the participation of
      each node in all subgraphs in a network. Smaller subgraphs are given more weight
      than larger ones, which makes this measure appropriate for characterizing network
      motifs. We show that the subgraph centrality [C(S)(i)] can be obtained
      mathematically from the spectra of the adjacency matrix of the network. This
      measure is better able to discriminate the nodes of a network than alternate
      measures such as degree, closeness, betweenness, and eigenvector centralities. We
      study eight real-world networks for which C(S)(i) displays useful and desirable
      properties, such as clear ranking of nodes and scale-free characteristics.
      Compared with the number of links per node, the ranking introduced by C(S)(i)
      (for the nodes in the protein interaction network of S. cereviciae) is more
      highly correlated with the lethality of individual proteins removed from the
      proteome.

PMID- 16089599
TI  - Diffusion-annihilation processes in complex networks.
AB  - We present a detailed analytical study of the A+A --> 0 diffusion-annihilation
      process in complex networks. By means of microscopic arguments, we derive a set
      of rate equations for the density of A particles in vertices of a given degree,
      valid for any generic degree distribution, and which we solve for uncorrelated
      networks. For homogeneous networks (with bounded fluctuations), we recover the
      standard mean-field solution, i.e., a particle density decreasing as the inverse
      of time. For heterogeneous (scale-free networks) in the infinite network size
      limit, we obtain instead a density decreasing as a power law, with an exponent
      depending on the degree distribution. We also analyze the role of finite size
      effects, showing that any finite scale-free network leads to the mean-field
      behavior, with a prefactor depending on the network size. We check our analytical
      predictions with extensive numerical simulations on homogeneous networks with
      Poisson degree distribution and scale-free networks with different degree
      exponents.

PMID- 16089600
TI  - Mean-field conductivity in a certain class of networks.
AB  - We consider resistor networks, which are lattices with bonds represented by
      conductors and some of the bonds removed. It is known that effective medium
      theories predict that the effective conductivity of such networks is a linear
      function of the number of bonds present above the percolation threshold, but
      exact results for completely random networks deviate from linearity. We show that
      if instead we take a randomly chosen tree spanning the lattice and then start
      adding bonds to it at random, the conductivity changes linearly with the number
      of added bonds and coincides with the effective medium result for a given bond
      concentration. We also make comparisons with some related models.

PMID- 16089601
TI  - Recurrence time analysis, long-term correlations, and extreme events.
AB  - The recurrence times between extreme events have been the central point of
      statistical analyses in many different areas of science. Simultaneously, the
      Poincare recurrence time has been extensively used to characterize nonlinear
      dynamical systems. We compare the main properties of these statistical methods
      pointing out their consequences for the recurrence analysis performed in time
      series. In particular, we analyze the dependence of the mean recurrence time and
      of the recurrence time statistics on the probability density function, on the
      interval whereto the recurrences are observed, and on the temporal correlations
      of time series. In the case of long-term correlations, we verify the validity of
      the stretched exponential distribution, which is uniquely defined by the exponent
      gamma, at the same time showing that it is restricted to the class of linear long
      term correlated processes. Simple transformations are able to modify the
      correlations of time series leading to stretched exponentials recurrence time
      statistics with different gamma, which shows a lack of invariance under the
      change of observables.

PMID- 16089602
TI  - Theory of lubrication due to collective pinning.
AB  - In collective pinning theory, the problem of two three-dimensional solids in
      contact is at its critical dimension. This implies that when the disordered
      forces acting between the two solids at the interface are relatively strong, the
      force of static friction should be large, but at smaller values of these forces,
      the system switches over to a regime of weak static friction. It is argued that
      this provides a mechanism for the reduction of friction in boundary lubrication.
      Lubricant molecules reduce static friction by smoothing the roughness of the
      surface, thus allowing the force pushing the surfaces together to be supported by
      more points of contact, which can switch the interface from the strong- to weak
      static-friction regime.

PMID- 16089603
TI  - Robustness of the avalanche dynamics in data-packet transport on scale-free
      networks.
AB  - We study the avalanche dynamics in the data-packet transport on scale-free
      networks through a simple model. In the model, each vertex is assigned a capacity
      proportional to the load with the proportionality constant 1+a . When the system
      is perturbed by a single vertex removal, the load of each vertex is
      redistributed, followed by subsequent failures of overloaded vertices. The
      avalanche size depends on the parameter a as well as which vertex triggers it. We
      find that there exists a critical value a(c) at which the avalanche size
      distribution follows a power law. The critical exponent associated with it
      appears to be robust as long as the degree exponent is between 2 and 3 and is
      close in value to that of the distribution of the diameter changes by single
      vertex removal.

PMID- 16089604
TI  - Dynamics of the Fisher information metric.
AB  - We present a method to generate probability distributions that correspond to
      metrics obeying partial differential equations generated by extremizing a
      functional J [g(mu nu) (theta(i)) ] , where g(mu nu) (theta(i)) is the Fisher
      metric. We postulate that this functional of the dynamical variable g(mu nu)
      (theta(i)) is stationary with respect to small variations of these variables. Our
      approach enables a dynamical approach to the Fisher information metric. It allows
      one to impose symmetries on a statistical system in a systematic way.

PMID- 16089605
TI  - Corrections to the Kelvin equation for long-range boundary fields.
AB  - The properties of a simple fluid, or Ising magnet, confined in an L x infinity
      geometry, are studied by means of numerical density-matrix renormalization-group
      techniques. Whereas the particle-particle interactions are short ranged, the wall
      particle interactions can be long ranged. Using a few complementary criteria the
      wetting transition line has been found for boundary fields with different ranges
      (including a marginal case) and its scaling form has been analyzed. A main goal
      was to analyze the influence of wetting on the scaling of the Kelvin equation,
      focusing on the leading correction term. We have found that at complete wetting
      the larger the range of the boundary fields, the smaller the region of anomalous
      corrections of type 1/L(4/3).

PMID- 16089606
TI  - Thermodynamics of the self-gravitating ring model.
AB  - We present the phase diagram, in both the microcanonical and the canonical
      ensemble, of the self-gravitating-ring (SGR) model, which describes the motion of
      equal point masses constrained on a ring and subject to 3D gravitational
      attraction. If the interaction is regularized at short distances by the
      introduction of a softening parameter, a global entropy maximum always exists,
      and thermodynamics is well defined in the mean-field limit. However, ensembles
      are not equivalent and a phase of negative specific heat in the microcanonical
      ensemble appears in a wide intermediate energy region, if the softening parameter
      is small enough. The phase transition changes from second to first order at a
      tricritical point, whose location is not the same in the two ensembles. All these
      features make of the SGR model the best prototype of a self-gravitating system in
      one dimension. In order to obtain the stable stationary mass distribution, we
      apply an iterative method, inspired by a previous one used in 2D turbulence,
      which ensures entropy increase and, hence, convergence towards an equilibrium
      state.

PMID- 16089607
TI  - Structural transitions in two-dimensional hard-sphere systems.
AB  - We spread randomly noncharged steel particles (diameter, 1.59 mm) on a silicon
      wafer to form a two-dimensional hard-sphere system. The particle structure versus
      the particle coverage was monitored. We observed the particle structural
      transition from liquidlike to triangular-lattice crystal-like with increasing
      particle coverage by analyzing the particle structure factor. The particle
      coverage at which the structural transition occurs was quantified by the curves
      of S(max) (A) and G6 (A); S(max) is the amplitude of the first peak of the
      structure factor (depicting the particle positional order), and G6 is the bond
      orientation order parameter. We also conducted a Monte Carlo simulation study.
      The Monte Carlo simulation results show good agreement with the experimental
      results at low particle area fractions. However, at high area fractions, the
      experimentally observed particle structure is less organized than that generated
      by simulations.

PMID- 16089608
TI  - Influence of the link weight structure on the shortest path.
AB  - The shortest path tree rooted at a source to all other nodes is investigated in a
      graph with polynomial link weights tunable by the power exponent alpha. By
      varying alpha, different types of shortest path trees, in short alpha trees,
      appear. Especially, the alpha --> 0 regime that corresponds to heavily
      fluctuating link weights possesses a peculiar type of tree. The most important
      properties of this alpha --> 0 tree are derived in the asymptotic limit for large
      N. The application of the theoretical insights to real networks (such as the
      Internet) are discussed: steering flow by adjusting link weights (traffic
      engineering), sensitivity of link weights and modeling of the network by alpha
      trees.

PMID- 16089609
TI  - Importance of extremists for the structure of social networks.
AB  - The structure and the properties of complex networks essentially depend on the
      way nodes get connected to each other. We assume here that each node has a
      feature which attracts the others. We model the situation by assigning two
      numbers to each node, omega and alpha, where omega indicates some property of the
      node and alpha the affinity towards that property. A node A is more likely to
      establish a connection with a node B if B has a high value of omega and A has a
      high value of alpha. Simple computer simulations show that networks built
      according to this principle have a degree distribution with a power-law tail,
      whose exponent is determined only by the nodes with the largest value of the
      affinity alpha (the "extremists"). This means that the extremists lead the
      formation process of the network and manage to shape the final topology of the
      system. The latter phenomenon may have implications in the study of social
      networks and in epidemiology.

PMID- 16089610
TI  - Spin-glass phase transition on scale-free networks.
AB  - We study the Ising spin-glass model on scale-free networks generated by the
      static model using the replica method. Based on the replica-symmetric solution,
      we derive the phase diagram consisting of the paramagnetic (P), ferromagnetic
      (F), and spin glass (SG) phases as well as the Almeida-Thouless line as functions
      of the degree exponent lambda, the mean degree K, and the fraction of
      ferromagnetic interactions r. To reflect the inhomogeneity of vertices, we modify
      the magnetization m and the spin-glass order parameter q with vertex- weights.
      The transition temperature T(c) (T(g)) between the P-F (P-SG) phases and the
      critical behaviors of the order parameters are found analytically. When
      2<lambda<3, T(c) and T(g) are infinite, and the system is in the F phase or the
      mixed phase for r>1/2, while it is in the SG phase at r=1/2. m and q decay as
      power-laws with increasing temperature with different lambda-dependent exponents.
      When lambda>3, the T(c) and T(g) are finite and related to the percolation
      threshold. The critical exponents associated with m and q depend on lambda for
      3<lambda<5 (3<lambda<4) at the P-F (P-SG) boundary.

PMID- 16089611
TI  - Compositional properties of random Boolean networks.
AB  - Random Boolean networks (RBNs) are used in a number of applications, including
      cell differentiation, immune response, evolution, gene regulatory networks, and
      neural networks. This paper addresses the problem of computing attractors in
      RBNs. An RBN with n vertices has up to 2(n) states. Therefore, for large n ,
      computing attractors by full enumeration of states is not feasible. The state
      space can be reduced by removing irrelevant vertices, which have no influence on
      the network's dynamics. In this paper, we show that attractors of an RBN can be
      computed compositionally from the attractors of the independent components of the
      subgraph induced by the relevant vertices of the network. The presented approach
      reduces the complexity of the problem from O (2(n)) to O (2(l)), where l is the
      number of relevant vertices in the largest component.

PMID- 16089612
TI  - Optimal spacing and penetration of cracks in a shrinking slab.
AB  - A method based on energy minimization is used to determine the spacing and
      penetration of a regular array of cracks in a slab that is shrinking due to a
      changing temperature field. The results show a range of different crack
      propagation behavior dependent on a single dimensionless parameter, being the
      ratio of the slab thickness and a characteristic length for the material. At low
      parameter values the minimum energy state can be achieved by continually adding
      more cracks until a steady state is achieved. At higher values, a minimum crack
      spacing is reached at finite time, beyond which the cracks are constrained to
      propagate with the minimum spacing. In the latter case, the uniform propagation
      is potentially unstable to a spatial period doubling, leading to increasingly
      complex crack penetration patterns. The energy minimization combined with the
      period doubling instability provides a means of determining the minimum energy
      state of cracks for all time. The problem considered here can be seen as a
      paradigm for cracking phenomena that occur on a large range of scales, from
      planetary to microscopic.

PMID- 16089613
TI  - Branching instabilities in rapid fracture: dynamics and geometry.
AB  - We propose a theoretical model for branching instabilities in 2-dimensional
      fracture, offering predictions for when crack branching occurs, how multiple
      cracks develop, and what is the geometry of multiple branches. The model is based
      on equations of motion for crack tips which depend only on the time dependent
      stress intensity factors. The latter are obtained by invoking an approximate
      relation between static and dynamic stress intensity factors, together with an
      essentially exact calculation of the static ones. The results of this model are
      in qualitative agreement with a number of experiments in the literature.

PMID- 16089614
TI  - Rate description of the stick-slip motion in friction force microscopy
      experiments.
AB  - During the stick-slip motion of an atomic force microscope tip contacting with a
      uniformly moving atomically clean surface, the force developed in the cantilever
      spring performs random sawtoothlike oscillations resulting from the thermally
      activated transitions of the tip from one surface site to the next. Using escape
      rate theory, the probability distribution of forces is calculated numerically to
      deduce the time-average lateral force as a function of pulling velocity. A
      transcendental equation for the average force is proposed and its approximate
      solution is obtained. The accuracy of this analytic approximation is demonstrated
      via comparison with the numerical results. The analogous force-velocity relations
      existing in the literature are shown to be the limiting cases of low and high
      cantilever spring constants of our analytic approximation.

PMID- 16089615
TI  - Application of the Gallavotti-Cohen fluctuation relation to thermostated steady
      states near equilibrium.
AB  - The fluctuation relation of the Gallavotti-Cohen fluctuation theorem (GCFT)
      concerns fluctuations in the phase-space compression rate of dissipative,
      reversible dynamical systems. It has been proven for Anosov systems, but it is
      expected to apply more generally. This raises the question of which non-Anosov
      systems satisfy the fluctuation relation. We analyze time-dependent fluctuations
      in the phase space compression rate of a class of N-particle systems that are at
      equilibrium or in near equilibrium steady states. This class does not include
      Anosov systems or isoenergetic systems; however, it includes most steady-state
      systems considered in molecular-dynamics simulations of realistic systems. We
      argue that the fluctuations of the phase-space compression rate of these systems
      at or near equilibrium do not satisfy the fluctuation relation of the GCFT,
      although the discrepancies become somewhat smaller as the systems move further
      from equilibrium. In contrast, similar fluctuation relations for an appropriately
      defined dissipation function appear to hold both near and far from equilibrium.

PMID- 16089616
TI  - Multifractal properties of the harmonic measure on Koch boundaries in two and
      three dimensions.
AB  - The multifractal properties of the harmonic measure on quadratic and cubic Koch
      boundaries are studied with the help of a new fast random walk algorithm adapted
      to these fractal geometries. The conjectural logarithmic development of local
      multifractal exponents is guessed for regular fractals and checked by extensive
      numerical simulations. This development allows one to compute the multifractal
      exponents of the harmonic measure with high accuracy, even with the first
      generations of the fractal. In particular, the information dimension in the case
      of the concave cubic Koch surface embedded in three dimensions is found to be
      slightly higher than its value D1 =2 for a smooth boundary.

PMID- 16089617
TI  - Directional crack propagation of granular water systems.
AB  - Pattern dynamics of directional crack propagation phenomena observed in drying
      process of starch-water mixture is investigated. To visualize the three
      dimensional structure of the drying-fracture process two kinds of experiments are
      performed, i.e., resin solidification planing method and real-time measurement of
      water content distribution with MR instruments. A cross section with polygonal
      structure is visualized in both experiments. The depth dependency of cell size is
      measured. The phenomenological model for water transportation is also discussed.

PMID- 16089618
TI  - One-dimensional Ising model built on small-world networks: competing dynamics.
AB  - In this paper, we offer a competing dynamic analysis of the one-dimensional Ising
      model built on the small-world network (SWN). Adding-type SWNs are investigated
      in detail using a simplified Hamiltonian of mean-field nature, and the result of
      rewiring-type is given because of the similarities of these two typical networks.
      We study the dynamical processes with competing Glauber mechanism and Kawasaki
      mechanism. The Glauber-type single-spin transition mechanism with probability p
      simulates the contact of the system with a heat bath and the Kawasaki-type
      dynamics with probability 1-p simulates an external energy flux. By studying the
      phase diagram obtained in the present work, we can realize some dynamical
      properties influenced by the small-world effect.

PMID- 16089619
TI  - Continuous majority-vote model.
AB  - We introduce a kinetic irreversible XY model and investigate its dynamic critical
      behavior through short-time Monte Carlo simulations on square lattices with
      periodic boundary conditions, starting from an ordered state. We find evidence
      that this system exhibits a Kosterlitz-Thouless-like phase for low values of the
      noise parameter. We present results for the correlation function exponent eta for
      several noise values. We also find that the dynamic critical exponent z is in
      agreement with the value expected for local update Monte Carlo rules.

PMID- 16089620
TI  - Critical adsorption at chemically structured substrates.
AB  - We consider binary liquid mixtures near their critical consolute points and
      exposed to geometrically flat but chemically structured substrates. The chemical
      contrast between the various substrate structures amounts to opposite local
      preferences for the two species of the binary liquid mixtures. Order parameter
      profiles are calculated for a chemical step, for a single chemical stripe, and
      for a periodic stripe pattern. The order parameter distributions exhibit
      frustration across the chemical steps which heals upon approaching the bulk. The
      corresponding spatial variation of the order parameter and its dependence on
      temperature are governed by universal scaling functions which we calculate within
      mean field theory. These scaling functions also determine the universal behavior
      of the excess adsorption relative to suitably chosen reference systems.

PMID- 16089621
TI  - Empirical mode decomposition and correlation properties of long daily ozone
      records.
AB  - Correlations for daily data of total ozone column are investigated by detrended
      fluctuation analysis (DFA). The removal of annual periodicity does not result in
      a background-free signal for the tropical station Mauna Loa. In order to identify
      the remaining quasiperiodic constituent, the relatively new method of empirical
      mode decomposition (EMD) is tested. We found that the so-called intrinsic mode
      functions do not represent real signal components of the ozone time series, their
      amplitude modulation is very sensitive to local changes such as random data
      removal or smoothing. Tests on synthetic data further corroborate the limitations
      of decomposing quasiperiodic signals from noise with EMD. Nevertheless the EMD
      algorithm helps to identify dominating frequencies in the time series, which
      allows to separate fluctuations from the remaining background. We demonstrate
      that DFA analysis for the cleaned Mauna Loa record yields scaling comparable to a
      mid-latitude station.

PMID- 16089622
TI  - Distribution of the largest aftershocks in branching models of triggered
      seismicity: theory of the universal Bath law.
AB  - Using the epidemic-type aftershock sequence (ETAS) branching model of triggered
      seismicity, we apply the formalism of generating probability functions to
      calculate exactly the average difference between the magnitude of a mainshock and
      the magnitude of its largest aftershock over all generations. This average
      magnitude difference is found empirically to be independent of the mainshock
      magnitude and equal to 1.2, a universal behavior known as Bath's law. Our theory
      shows that Bath's law holds only sufficiently close to the critical regime of the
      ETAS branching process. Allowing for error bars +/- 0.1 for Bath's constant value
      around 1.2, our exact analytical treatment of Bath's law provides new constraints
      on the productivity exponent alpha and the branching ratio n: 0.9 approximately <
      alpha < or =1. We propose a method for measuring alpha based on the predicted
      renormalization of the Gutenberg-Richter distribution of the magnitudes of the
      largest aftershock. We also introduce the "second Bath law for foreshocks:" the
      probability that a main earthquake turns out to be the foreshock does not depend
      on its magnitude rho.

PMID- 16089623
TI  - Entropy and density of states from isoenergetic nonequilibrium processes.
AB  - Two identities in statistical mechanics involving entropy differences (or ratios
      of densities of states) at constant energy are derived. The first provides a
      nontrivial extension of the Jarzynski equality to the microcanonical ensemble [C.
      Jarzynski, Phys. Rev. Lett. 78, 2690 (1997)], which can be seen as a "fast
      switching" version of the adiabatic switching method for computing entropies [M.
      Watanabe and W. P. Reinhardt, Phys. Rev. Lett. 65, 3301 (1990)]. The second is a
      thermodynamic integration formula analogous to a well-known expression for free
      energies, and follows after taking the quasistatic limit of the first. Both
      identities can be conveniently used in conjunction with a scaling relation
      (herein derived) that allows one to extrapolate measurements taken at a single
      energy to a wide range of energy values. Practical aspects of these identities in
      the context of numerical simulations are discussed.

PMID- 16089624
TI  - Exact dynamics of a reaction-diffusion model with spatially alternating rates.
AB  - We present the exact solution for the full dynamics of a nonequilibrium spin
      chain and its dual reaction-diffusion model, for arbitrary initial conditions.
      The spin chain is driven out of equilibrium by coupling alternating spins to two
      thermal baths at different temperatures. In the reaction-diffusion model, this
      translates into spatially alternating rates for particle creation and
      annihilation, and even negative "temperatures" have a perfectly natural
      interpretation. Observables of interest include the magnetization, the particle
      density, and all correlation functions for both models. Two generic types of time
      dependence are found: if both temperatures are positive, the magnetization,
      density, and correlation functions decay exponentially to their steady-state
      values. In contrast, if one of the temperatures is negative, damped oscillations
      are observed in all quantities. They can be traced to a subtle competition of
      pair creation and annihilation on the two sublattices. We comment on the
      limitations of mean-field theory and propose an experimental realization of our
      model in certain conjugated polymers and linear chain compounds.

PMID- 16089625
TI  - Extreme times in financial markets.
AB  - We apply the theory of continuous time random walks (CTRWs) to study some aspects
      involving extreme events in financial time series. We focus our attention on the
      mean exit time (MET). We derive a general equation for this average and compare
      it with empirical results coming from high-frequency data of the U.S. dollar and
      Deutsche mark futures market. The empirical MET follows a quadratic law in the
      return length interval which is consistent with the CTRW formalism.

PMID- 16089626
TI  - Magnetic models on Apollonian networks.
AB  - Thermodynamic and magnetic properties of Ising models defined on the triangular
      Apollonian network are investigated. This and other similar networks are inspired
      by the problem of covering a Euclidian domain with circles of maximal radii. Maps
      for the thermodynamic functions in two subsequent generations of the construction
      of the network are obtained by formulating the problem in terms of transfer
      matrices. Numerical iteration of this set of maps leads to very precise values
      for the thermodynamic properties of the model. Different choices for the coupling
      constants between only nearest neighbors along the lattice are taken into
      account. For both ferromagnetic and antiferromagnetic constants, long-range
      magnetic ordering is obtained. With exception of a size-dependent effective
      critical behavior of the correlation length, no evidence of asymptotic
      criticality was detected.

PMID- 16089627
TI  - Monte Carlo rejection as a tool for measuring the energy landscape scaling of
      simple fluids.
AB  - A simple modification of the Monte Carlo algorithm is proposed to explore the
      topography and the scaling of the energy landscape. We apply this idea to a
      simple hard-core fluid. The results for different packing fractions show a power
      law scaling of the landscape boundary, with a characteristic scale that separates
      the values of the scaling exponents. Finally, it is shown how the topology
      determines the freezing point of the system due to the increasing importance and
      complexity of the boundary.

PMID- 16089628
TI  - Onset of chaotic symbolic synchronization between population inversions in an
      array of weakly coupled Bose-Einstein condensates.
AB  - We investigate the onset of chaotic dynamics of the one-dimensional discrete
      nonlinear Schrodinger equation with periodic boundary conditions in the presence
      of a single on-site defect. This model describes a ring of weakly coupled Bose
      Einstein condensates with attractive interactions. We focus on the transition to
      global stochasticity in three different scenarios as the defect is changed. We
      make use of a suitable Poincare section and study different families of
      stationary solutions, where certain bifurcations lead to global stochasticity.
      The global stochasticity is characterized by chaotic symbolic synchronization
      between the population inversions of certain pairs of condensates. We have seen
      that the Poincare cycles are useful to gain insight in the dynamics of this
      Hamiltonian system. Indeed, the return maps of the Poincare cycles have been used
      successfully to follow the orbit along the stochastic layers of different
      resonances in the chaotic self-trapping regime. Moreover, the time series of the
      Poincare cycles suggests that in the global stochasticity regime the dynamics is,
      to some extent, Markovian, in spite of the fact that the condensates are phase
      locked with almost the same phase. This phase locking induces a peculiar local
      interference of the matter waves of the condensates.

PMID- 16089629
TI  - Quantum chaos algorithms and dissipative decoherence with quantum trajectories.
AB  - Using the methods of quantum trajectories we investigate the effects of
      dissipative decoherence in a quantum computer algorithm simulating dynamics in
      various regimes of quantum chaos including dynamical localization, the quantum
      ergodic regime, and quasi-integrable motion. As an example we use the quantum
      sawtooth algorithm which can be implemented in a polynomial number of quantum
      gates. It is shown that the fidelity of quantum computation decays exponentially
      with time and that the decay rate is proportional to the number of qubits, number
      of quantum gates, and per gate dissipation rate induced by external decoherence.
      In the limit of strong dissipation the quantum algorithm generates a quantum
      attractor which may have a complex or simple structure. We also compare the
      effects of dissipative decoherence with the effects of static imperfections.

PMID- 16089630
TI  - Interplay between noise and boundary conditions in pattern formation in adsorbed
      substances.
AB  - We have studied the interplay between noise and boundary conditions on the
      possibility of noise induced pattern formation. With this aim, we have exploited
      a deterministic model for pattern formation in adsorbed substances--including the
      effect of lateral interactions--used to describe the phenomenon of adsorption in
      surfaces, where a multiplicative noise fulfilling a fluctuation-dissipation
      relation was added. We have found solutions for different boundary conditions,
      particularly corresponding to two stable and one unstable patterns, where one of
      the stable and the unstable one, are purely induced by the multiplicative noise.
      In the case of albedo boundary conditions we have found a transition from
      monostable to a noise induced bistable behavior as the albedo parameter is
      varied.

PMID- 16089631
TI  - Synchronization of spectral components and its regularities in chaotic dynamical
      systems.
AB  - The chaotic synchronization regime in coupled dynamical systems is considered. It
      has been shown that the onset of a synchronous regime is based on the appearance
      of a phase relation between the interacting chaotic oscillator frequency
      components of Fourier spectra. The criterion of synchronization of spectral
      components as well as the measure of synchronization has been discussed. The
      universal power law has been described. The main results are illustrated by
      coupled Rossler systems, Van der Pol and Van der Pol-Duffing oscillators.

PMID- 16089632
TI  - Ising-Bloch transition for the parametric Ginzburg-Landau equation with rapidly
      varying perturbations.
AB  - We study the effects of rapid periodic and stochastic modulations of parameters
      in systems described by the complex parametric Ginzburg-Landau equation.
      Amplitude equations, which govern the dynamics of the field averaged over the
      rapid modulations, are derived. For temporal modulations of the linear detuning
      the threshold for the transition from Ising to Bloch walls is shifted depending
      on the strength of the perturbation. In contrast to this, rapid perturbations of
      the linear gain lead only to a decrease of the amplitude of both wall types
      leaving the bifurcation point of the Ising-Bloch transition unchanged. Stochastic
      perturbations of the detuning lead to a Brownian motion of the Bloch wall beyond
      bifurcation where the velocity is given analytically. All theoretical predictions
      are confirmed by numerical simulations of the full stochastic Ginzburg-Landau
      equation.

PMID- 16089633
TI  - Emulation of quantum mechanical billiards by electrical resonance circuits.
AB  - We propose that a two-dimensional electric network may be used for fundamental
      studies of wave function properties, transport, and related statistics. Using
      Kirchhoff's current law and the j omega method we find that the network is
      analogous to a discretized Schrodinger equation for quantum billiards and dots.
      Thus complex electric potentials play the role of quantum mechanical wave
      functions. Ways of realizing the electric network are discussed briefly. The role
      of symmetries is outlined, and a direct way of selecting states with a given
      symmetry is presented.

PMID- 16089634
TI  - Spatiotemporal coding in an electrochemical oscillatory network.
AB  - A network consisting of N relaxation electrochemical oscillators, mutually
      coupled by all-to-all inhibitory connections, can have (N-1) ! coexisting out-of
      phase states, each state being a permutation of a periodic spiking sequence. The
      modification of the out-of-phase states by shots of laser pulse perturbations is
      shown. In such networks the phase relation of the oscillators is stored as a
      coded pattern. The ability of the network to function as a rewritable memory of
      (N-1) ! different spatiotemporal patterns is demonstrated experimentally for N=4.

PMID- 16089635
TI  - Classical dynamics of two-electron atoms near the triple collision.
AB  - The classical dynamics of two electrons in the Coulomb potential of an attractive
      nucleus is chaotic in large parts of the high-dimensional phase space. Quantum
      spectra of two-electron atoms, however, exhibit structures which clearly hint at
      the existence of approximate symmetries in this system. In a recent paper [Phys.
      Rev. Lett. 93, 054302 (2004)], we presented a study of the dynamics near the
      triple collision as a first step towards uncovering the hidden regularity in the
      classical dynamics of two electron atoms. The nonregularizable triple collision
      singularity is a main source of chaos in three body Coulomb problems. Here, we
      will give a more detailed account of our findings based on a study of the global
      structure of the stable and unstable manifolds of the triple collision.

PMID- 16089636
TI  - Synchronized chaotic intermittent and spiking behavior in coupled map chains.
AB  - We study phase synchronization effects in a chain of nonidentical chaotic
      oscillators with a type-I intermittent behavior. Two types of parameter
      distribution, linear and random, are considered. The typical phenomena are the
      onset and existence of global (all-to-all) and cluster (partial) synchronization
      with increase of coupling. Increase of coupling strength can also lead to
      desynchronization phenomena, i.e., global or cluster synchronization is changed
      into a regime where synchronization is intermittent with incoherent states. Then
      a regime of a fully incoherent nonsynchronous state (spatiotemporal
      intermittency) appears. Synchronization-desynchronization transitions with
      increase of coupling are also demonstrated for a system resembling an
      intermittent one: a chain of coupled maps replicating the spiking behavior of
      neurobiological networks.

PMID- 16089637
TI  - Stiff stability of the hydrogen atom in dissipative Fokker electrodynamics.
AB  - We introduce an ad hoc electrodynamics with advanced and retarded Lienard
      Wiechert interactions plus the dissipative Lorentz-Dirac self-interaction force.
      We study the covariant dynamical system of the electromagnetic two-body problem,
      i.e., the hydrogen atom. We perform the linear stability analysis of circular
      orbits for oscillations perpendicular to the orbital plane. In particular, we
      study the normal modes of the linearized dynamics that have an arbitrarily large
      imaginary eigenvalue. These large eigenvalues are fast frequencies that introduce
      a fast (stiff) time scale into the dynamics. As an application, we study the
      phenomenon of resonant dissipation, i.e., a motion where both particles recoil
      together in a drifting circular orbit (a bound state), while the atom dissipates
      center-of-mass energy only. This balancing of the stiff dynamics is established
      by the existence of a quartic resonant constant that locks the dynamics to the
      neighborhood of the recoiling circular orbit. The resonance condition quantizes
      the angular momenta in reasonable agreement with the Bohr atom. The principal
      result is that the emission lines of quantum electrodynamics agree with the
      prediction of our resonance condition within 1% average deviation.

PMID- 16089638
TI  - Irreversible evolution of quantum chaos.
AB  - The pendulum is the simplest system having all the basic properties inherent in
      dynamic stochastic systems. In the present paper we investigate the pendulum with
      the aim to reveal the properties of a quantum analogue of dynamic stochasticity
      or, in other words, to obtain the basic properties of quantum chaos. It is shown
      that a periodic perturbation of the quantum pendulum (similarly to the classical
      one) in the neighborhood of the separatrix can bring about irreversible
      phenomena. As a result of recurrent passages between degenerate states, the
      system gets self-chaotized and passes from the pure state to the mixed one.
      Chaotization involves the states, the branch points of whose levels participate
      in a slow "drift" of the system along the Mathieu characteristics this "drift"
      being caused by a slowly changing variable field. Recurrent relations are
      obtained for populations of levels participating in the irreversible evolution
      process. It is shown that the entropy of the system first grows and, after
      reaching the equilibrium state, acquires a constant value.

PMID- 16089639
TI  - Correlation function bootstrapping in quantum chaotic systems.
AB  - We discuss a general and efficient approach for "bootstrapping" short-time
      correlation data in chaotic or complex quantum systems to obtain information
      about long-time dynamics and stationary properties, such as the local density of
      states. When the short-time data are sufficient to identify an individual quantum
      system, we obtain a systematic approximation for the spectrum and wave functions.
      Otherwise, we obtain statistical properties, including wave function intensity
      distributions, for an ensemble of all quantum systems sharing the given short
      time correlations. The results are valid for open or closed systems, and are
      stable under perturbation of the short-time input data. Numerical examples
      include quantum maps and two-dimensional anharmonic oscillators.

PMID- 16089640
TI  - Topological singularities and transport in kicked Harper model.
AB  - Quasienergy spectrum of kicked Harper model is found to exhibit a series of
      diabolic crossings. These conical degeneracies reside mostly on the symmetry line
      of its two-dimensional parameter space and their locations are found to coincide
      with the local maxima of the kinetic energy of the kicked system. Additionally,
      there are exceptional point singularities, that are found by analytically
      continuing the kicking parameter in the complex plane. The location of these
      singularities appear to be correlated with the localization of the quantum wave
      packet. These studies suggest a correlation between the transport and the
      topological characteristics of the system.

PMID- 16089641
TI  - Mechanism of bistability: tonic spiking and bursting in a neuron model.
AB  - Neurons can demonstrate various types of activity; tonically spiking, bursting as
      well as silent neurons are frequently observed in electrophysiological
      experiments. The methods of qualitative theory of slow-fast systems applied to
      biophysically realistic neuron models can describe basic scenarios of how these
      regimes of activity can be generated and transitions between them can be made.
      Here we demonstrate that a bifurcation of a codimension one can explain a
      transition between tonic spiking behavior and bursting behavior. Namely, we argue
      that the Lukyanov-Shilnikov bifurcation of a saddle-node periodic orbit with
      noncentral homoclinics may initiate a bistability observed in a model of a leech
      heart interneuron under defined pharmacological conditions. This model can
      exhibit two coexisting types of oscillations: tonic spiking and bursting,
      depending on the initial state of the neuron model. Moreover, the neuron model
      also generates weakly chaotic bursts when a control parameter is close to the
      bifurcation values that correspond to homoclinic bifurcations of a saddle or a
      saddle-node periodic orbit.

PMID- 16089642
TI  - Universal statistics of the scattering coefficient of chaotic microwave cavities.
AB  - We consider the statistics of the scattering coefficient S of a chaotic microwave
      cavity coupled to a single port. We remove the nonuniversal effects of the
      coupling from the experimental S data using the radiation impedance obtained
      directly from the experiments. We thus obtain the normalized scattering
      coefficient whose probability density function (PDF) is predicted to be universal
      in that it depends only on the loss (quality factor) of the cavity. We compare
      experimental PDFs of the normalized scattering coefficients with those obtained
      from random matrix theory (RMT), and find excellent agreement. The results apply
      to scattering measurements on any wave chaotic system.

PMID- 16089643
TI  - Shape and stability of a viscous thread.
AB  - When a viscous fluid, like oil or syrup, streams from a small orifice and falls
      freely under gravity, it forms a long slender thread, which can be maintained in
      a stable, stationary state with lengths up to several meters. We discuss the
      shape of such liquid threads and their surprising stability. The stationary
      shapes are discussed within the long-wavelength approximation and compared to
      experiments. It turns out that the strong advection of the falling fluid can
      almost outrun the Rayleigh-Plateau instability. The asymptotic shape and
      stability are independent of viscosity and small perturbations grow with time as
      exp (C t(1/4)), where the constant is independent of viscosity. The corresponding
      spatial growth has the form exp [(z/L)(1/8)], where z is the down stream distance
      and L approximately Q(2) sigma(-2) g and where sigma is the surface tension
      divided by density, g is the gravity, and Q is the flux. We also show that a slow
      spatial increase of the gravitational field can make the thread stable.

PMID- 16089644
TI  - Marangoni-driven instabilities of an evaporating liquid-vapor interface.
AB  - Marangoni-driven instabilities of a liquid-vapor interface of ethanol formed in a
      horizontally oriented capillary tube of 600 microm diameter are described.
      Instabilities of the interface are reported as well as instabilities of the
      liquid flow underneath the meniscus. The experimental results consist of visual
      observation of the interface, microscale particle image velocimetry measurements
      of the liquid flow and ir temperature measurements of the interface. The
      instabilities are found in both the flow structure and the interfacial
      temperature which present a periodic oscillatory pattern with a characteristic
      frequency of about 5 Hz. The interface also oscillates periodically, having a
      characteristic frequency of about 1.4 Hz. The differential evaporative cooling
      along the extended meniscus in the triple-line region produces a temperature
      difference which sustains the liquid-thermocapillary Marangoni-driven convection.
      A linear stability analysis based on a one-sided model, modified to take into
      account evaporation, is used to show that the self-induced temperature difference
      at the triple-line region is responsible for the observed interfacial
      instabilities. The instabilities in the flow pattern are due to competition
      between the surface tension driving force and gravity and are also found to be
      influenced by the meniscus instabilities.

PMID- 16089645
TI  - Thermal convection in colloidal suspensions with negative separation ratio.
AB  - Thermal convection in colloidal suspensions of nanosized particles is
      investigated. Representative examples for such materials are ferrofluids, but
      since we do not imply any external magnetic field, the description applies to
      nonmagnetic suspensions as well. With the grain size being large on molecular
      length scales, the particle mobility is extremely small, allowing to disregard
      the concentration dynamics in most cases. However, due to the pronounced Soret
      effect of these materials in combination with a considerable solutal expansion,
      this cannot be done when thermal convection is under consideration. Here we
      consider the case when the separation ratio (the Soret coefficient) is negative.
      This case reveals a much richer variety of phenomena than that of positive
      separation ratio. In particular, for heating from below we find a linear
      oscillatory instability, whose amplitude, however, relaxes to zero on the long
      turn and is thus transient only and, at higher Rayleigh numbers, a finite
      amplitude stationary instability coexistent with the linearly stable convection
      free state. By heating from above short-length-scale convective structures occur,
      whose wavelength depends on the Rayleigh number.

PMID- 16089646
TI  - Numerical study of miscible fingering in a time-dependent gap Hele-Shaw cell.
AB  - We perform a detailed numerical study of the evolution of a miscible fluid
      droplet in a time-dependent gap Hele-Shaw cell. The development of the emerging
      fingering instabilities is systematically analyzed by intensive and highly
      accurate numerical simulations. We focus on the influence of three relevant
      physical parameters on the interface dynamics: the Pelclet number Pe, the
      viscosity contrast A, and the Korteweg stress parameter delta. Consistently with
      conventional miscible Saffman-Taylor studies in constant-gap Hele-Shaw cells, our
      results demonstrate that more vigorous fingering is observed at higher Pe and
      larger A. Concerning the specific role of Pe and A, we deduce two general
      results: higher Peclet number favors branching around a nearly circular region
      (which leads to longer interfacial lengths); while larger viscosity contrast
      results in more significant finger penetrations (which is quantitatively
      expressed by larger diameter of gyration). We have also verified that the
      Korteweg stress parameter delta does act as an effective interfacial tension: it
      stabilizes the miscible interface, leading to fingering patterns that present a
      greater resemblance with the structures obtained in similar immiscible
      situations. Finally, we have identified the development of a visually striking
      phenomenon in the limit of high Pe, large A , and relatively small delta: some
      outward fingers pinch, and subsequent droplet detachment is observed. We show
      that such a droplet detachment process can be prevented by the action of stronger
      interfacial stresses. This last finding provides additional evidence for the
      claim that the Korteweg stresses can be treated as an ersatz interfacial tension
      in diffusing fluids.

PMID- 16089647
TI  - Global picture of self-similar and non-self-similar decay in Burgers turbulence.
AB  - This paper continues earlier investigations of the decay of Burgers turbulence in
      one dimension from Gaussian random initial conditions of the power-law spectral
      type E0(k) approximately |k|(n). Depending on the power n , different
      characteristic regions are distinguished. The main focus of this paper is to
      delineate the regions in wave number k and time t in which self-similarity can
      (and cannot) be observed, taking into account small-k and large-k cutoffs. The
      evolution of the spectrum can be inferred using physical arguments describing the
      competition between the initial spectrum and the new frequencies generated by the
      dynamics. For large wave numbers, we always have a k(-2) region, associated with
      the shocks. When n is less than 1, the large-scale part of the spectrum is
      preserved in time and the global evolution is self-similar, so that scaling
      arguments perfectly predict the behavior in time of the energy and integral
      scale. If n is larger than 2, the spectrum tends for long times to a universal
      scaling form independent of the initial conditions, with universal behavior k(2)
      at small wave numbers. In the interval 2<n the leading behavior is self-similar,
      independent of n and with universal behavior k(2) at small wave number. When
      1<n<2, the spectrum has three scaling regions: first, a |k|(n) region at very
      small k's with a time-independent constant; second, a k(2) region at intermediate
      wave numbers; finally, the usual k(-2) region. In the remaining interval n<-3 the
      small-k cutoff dominates and n also plays no role. We find also (numerically) the
      subleading term approximately k(2) in the evolution of the spectrum in the
      interval -3<n<1. High-resolution numerical simulations have been performed
      confirming both scaling predictions and analytical asymptotic theory.

PMID- 16089648
TI  - Electrohydrodynamics of binary electrolytes driven by modulated surface
      potentials.
AB  - We study the electrohydrodynamics of the Debye screening layer that arises in an
      aqueous binary solution near a planar insulating wall when applying a spatially
      modulated ac voltage. Combining this with first order perturbation theory we
      establish the governing equations for the full nonequilibrium problem and obtain
      analytic solutions in the bulk for the pressure and velocity fields of the
      electrolyte and for the electric potential. We find good agreement between the
      numerics of the full problem and the analytics of the linear theory. Our work
      provides the theoretical foundations of circuit models discussed in the
      literature. The nonequilibrium approach also reveals unexpected high-frequency
      dynamics not predicted by circuit models.

PMID- 16089649
TI  - Influence of excitation wave forms and frequencies on the fundamental time
      symmetry of the system dynamics, studied in nematic electroconvection.
AB  - The dynamics of periodically driven nematic electroconvection, a classical
      dissipative pattern forming system, is studied experimentally and theoretically.
      We demonstrate that for certain excitation wave forms, the system's dynamic
      response can be periodic with the excitation or subharmonic, depending on the
      periodicity of the excitation as control parameter, while for some classes of
      wave forms, a subharmonic response seems to be principally excluded. In
      particular, we describe influences of frequency and time symmetry of triangular
      excitation wave forms. Two intrinsically different routes for the transition to
      subharmonic dynamics are observed. The time characteristics of the system
      variables are determined by numerical solution of appropriate model equations and
      a Floquet analysis. Experimental data are compared to calculations of the model
      system of two coupled linear differential equations. Results of experiment and
      model are in excellent agreement.

PMID- 16089650
TI  - Multiple translational temperature model and its shock structure solution.
AB  - Within a shock layer, the translational motion of the gas is more energetic in
      the direction perpendicular to the shock front than in the direction parallel to
      the shock. To predict this translational nonequilibrium, a generalized gas
      kinetic BGK model is proposed. With the adaptation of a continuum gas
      distribution function truncated up to the Navier-Stokes order and a generalized
      particle collision time, this newly constructed kinetic model is used in the
      monatomic gas shock structure calculations, where two translational temperatures
      inside the shock layer are well captured.

PMID- 16089651
TI  - Proposed method to estimate the liquid-vapor accommodation coefficient based on
      experimental sonoluminescence data.
AB  - We used the temporal evolution of the bubble radius in single-bubble
      sonoluminescence to estimate the water liquid-vapor accommodation coefficient.
      The rapid changes in the bubble radius that occur during the bubble collapse and
      rebounds are a function of the actual value of the accommodation coefficient. We
      selected bubble radius measurements obtained from two different experimental
      techniques in conjunction with a robust parameter estimation strategy and we
      obtained that for water at room temperature the mass accommodation coefficient is
      in the confidence interval [0.217,0.329].

PMID- 16089652
TI  - Intermittency of acceleration in isotropic turbulence.
AB  - The intermittency of acceleration is investigated for isotropic turbulence using
      direct numerical simulation. Intermittently found acceleration of large magnitude
      always points towards the rotational axis of a vortex filament, indicating that
      the intermittency of acceleration is associated with the rotational motion of the
      vortices that causes centripetal acceleration, which is consistent with the
      reported result for the near-wall turbulence. Furthermore, investigation on
      movements of such vortex filaments provides some insights into the dynamics of
      local dissipation, enstrophy and acceleration. Strong dissipation partially
      covering the edge of a vortex filament shows weak correlation with enstrophy,
      while it is strongly correlated with acceleration.

PMID- 16089653
TI  - Two-loop calculation of the turbulent Prandtl number.
AB  - The turbulent Prandtl number has been calculated in the two-loop approximation of
      the epsilon expansion of the stochastic theory of turbulence. The strikingly
      small value obtained for the two-loop correction explains the good agreement of
      the earlier one-loop result with the experiment. This situation is drastically
      different from other available nontrivial two-loop results, which exhibit
      corrections of the magnitude of the one-loop term. The reason is traced to the
      mutual cancellation of additional divergences appearing in two dimensions, which
      have had a major effect on the results of previous calculations of other
      quantities.

PMID- 16089654
TI  - Force field inside the void in complex plasmas under microgravity conditions.
AB  - Observations of complex plasmas under microgravity conditions onboard the
      International Space Station performed with the Plasma-Kristall experiment-Nefedov
      facility are reported. A weak instability of the boundary between the central
      void (region free of microparticles) and the microparticle cloud is observed at
      low gas pressures. The instability leads to periodic injections of a relatively
      small number of particles into the void region (by analogy this effect is called
      the "trampoline effect"). The trajectories of injected particles are analyzed
      providing information on the force field inside the void. The experimental
      results are compared with theory which assumes that the most important forces
      inside the void are the electric and the ion drag forces. Good agreement is found
      clearly indicating that under conditions investigated the void formation is
      caused by the ion drag force.

PMID- 16089655
TI  - Electron-temperature and energy-flow history in an imploding plasma.
AB  - The time-dependent radial distribution of the electron temperature in a 0.6
      micros, 220-kA gas-puff z-pinch plasma is studied using spatially-resolved
      observations of line emission from singly to fivefold ionized oxygen ions during
      the plasma implosion, up to 50 ns before maximum compression. The temperature
      obtained, together with the previously determined radial distributions of the
      electron density, plasma radial velocity, and magnetic field, allows for studying
      the history of the magnetic-field energy coupling to the plasma by comparing the
      energy deposition and dissipation rates in the plasma. It is found that at this
      phase of the implosion, approximately 65% of the energy deposited in the plasma
      is imparted to the plasma radial flow, with the rest of the energy being
      converted into internal energy and radiation.

PMID- 16089656
TI  - High-energy proton generation and suppression of transverse proton divergence by
      localized electrons in a laser-foil interaction.
AB  - A suppression of a transverse divergence of high-energy protons generated by an
      interaction of a laser with a thin slab foil is investigated in this paper by 2.5
      dimensional particle-in-cell simulations. When an intense (approximately 10(24)
      W/m(2)) short-pulse (a few ten femtoseconds) laser illuminates a thin foil target
      of a hydrogen, foil electrons are accelerated and compressed longitudinally by a
      laser light pressure and fast electron bunches are produced in the thin foil
      target. The fast electron bunches pass through the foil target, and a strong
      magnetic field is produced near the opposite side of the foil target. Because the
      strong magnetic field confines the electrons, a localization of the electrons is
      observed at the opposite side of a laser illumination surface. The local electron
      bunch produces not only a longitudinal electric field, but also a transverse
      electric field, which is directed toward the laser axis. Protons are accelerated
      and extracted from the foil, and the proton bunch divergence is successfully
      suppressed by the transverse electric field.

PMID- 16089657
TI  - Ionization processes in fluorescent lamps: evaluation of the Hg chemi-ionization
      rate coefficients.
AB  - Chemi-ionization by two mercury atoms to produce mercury atomic and molecular
      ions has been considered an important process in fluorescent lamps (FLs) for a
      quarter of a century. Despite the absence of reliable data, these processes have
      been included in a number of numerical models to help explain some of the
      experimental observations. These models have shown that the most important
      process is the Penning ionization of two Hg metastable atoms
      Hg(6(3)P2)+Hg(6(3)P2) --> Hg(+)+Hg(6(1)S0)+e. Although there is no experimental
      measurement of this cross section, modelers have typically used values implied
      from measurements of other chemi-ionization cross sections, or values obtained by
      fitting parameters to numerical models to obtain agreement with experiment.
      Recent theoretical investigations have indicated that the cross sections for the
      important processes may not be as large as previously thought. The aim of the
      present paper is to critically review the historical development of studies of
      chemi-ionization in fluorescent lamps and to present new experimental evidence
      which is consistent with the theoretical calculations and contradicts the
      conclusions from previously published experiments.

PMID- 16089658
TI  - Viscosity and mutual diffusion in strongly asymmetric binary ionic mixtures.
AB  - We present molecular dynamics simulation results for the viscosity and mutual
      diffusion constant of a strongly asymmetric binary ionic mixture. We compare the
      results with available theoretical models previously tested for much smaller
      asymmetries. For the case of viscosity we propose a predictive framework based on
      the linear mixing rule, while for mutual diffusion we discuss some consistency
      problems of widely used Boltzmann-equation-based models.

PMID- 16089659
TI  - Criticality in a Vlasov-Poisson system: a fermioniclike universality class.
AB  - A model Vlasov-Poisson system is simulated close to the point of marginal
      stability, thus assuming only the wave-particle resonant interactions are
      responsible for saturation, and shown to obey the power-law scaling of a second
      order phase transition. The set of critical exponents analogous to those of the
      Ising universality class is calculated and shown to obey the Widom and Rushbrooke
      scaling and Josephson's hyperscaling relations at the formal dimensionality d=5
      below the critical point at nonzero order parameter. However, the two-point
      correlation function does not correspond to the propagator of Euclidean quantum
      field theory, which is the Gaussian model for the Ising universality class.
      Instead, it corresponds to the propagator for the fermionic vector field and to
      the upper critical dimensionality d(c) = 2. This suggests criticality of
      collisionless Vlasov-Poisson systems corresponds to a universality class
      analogous to that of critical phenomena of a fermionic quantum field description.

PMID- 16089660
TI  - Charged state of a spherical plasma in vacuum.
AB  - The stationary state of a spherically symmetric plasma configuration is
      investigated in the limit of immobile ions and weak collisions. Configurations
      with small radii are positively charged as a significant fraction of the electron
      population evaporates during the equilibration process, leaving behind an
      electron distribution function with an energy cutoff. Such charged plasma
      configurations are of interest for the study of Coulomb explosions and ion
      acceleration from small clusters irradiated by ultraintense laser pulses and for
      the investigation of ion bunches propagation in a plasma.

PMID- 16089661
TI  - Collisional absorption of dense plasmas in strong laser fields: quantum
      statistical results and simulation.
AB  - Collisional absorption of dense fully ionized plasmas in strong laser fields is
      investigated using quantum statistical methods as well as molecular dynamics
      simulations. For high-frequency fields, quantum statistical expressions for the
      electrical current density and the electron-ion collision frequency are
      presented. Strong correlations are taken into account and their influence on the
      absorption rate is discussed. The expressions are valid for arbitrary field
      strength assuming the nonrelativistic case. In addition, molecular dynamics
      simulations were performed to calculate the heating of dense plasmas in laser
      fields. Comparisons with the analytic results for different plasma parameters are
      given. There are considered the cases of isothermal plasmas as well as two
      temperature plasmas. Furthermore, results for the velocity distribution function
      under the influence of intense laser fields are presented which show a different
      behavior in comparison to weak fields.

PMID- 16089662
TI  - Nonlinear deformations of liquid-liquid interfaces induced by electromagnetic
      radiation pressure.
AB  - The idea of working with a near-critical phase-separated liquid mixture whereby
      the surface tension becomes weak, has recently made the field of laser
      manipulation of liquid interfaces a much more convenient tool in practice. The
      deformation of interfaces may become as large as several tenths of micrometers,
      even with the use of conventional laser power. This circumstance necessitates the
      use of nonlinear geometrical theory for the description of surface deformations.
      The present paper works out such a theory, for the surface deformation under
      conditions of axial symmetry and stationarity. Good agreement is found with the
      experimental results of Casner and Delville [A. Casner and J. P. Delville, Phys.
      Rev. Lett. 87, 054503 (2001); Opt. Lett. 26, 1418 (2001); Phys. Rev. Lett. 90,
      144503 (2003)], in the case of moderate power or a broad laser beam. In the case
      of large power and a narrow beam, corresponding to surface deformations of about
      50 micrometers or higher, the theory is found to over-predict the deformation.
      Possible explanations of this discrepancy are discussed.

PMID- 16089663
TI  - Point defect geometries in inverted opal photonic crystals.
AB  - We study point defect geometries in inverted opal photonic crystals that can be
      easily fabricated by means of colloidal self-assembly. Two broad classes of
      defects are considered: substitutional and interstitial. Substitutional point
      defects are found to introduce a usable defect band into the photonic band gap.
      This can be done by using a silica sphere of radius between 0.33a and 0.35a
      (where a is the lattice constant). The state is triply degenerate. Reflectance
      and local density of states calculations are performed to verify the existence
      and frequency of this defect. The point defect can be made by precoating shrunk
      silica spheres with a thin layer of silicon. Such a defect can be used as a
      microcavity for localizing light at a point, with a quality factor Q that is
      limited primarily by the proximity of the defect to the surface of the photonic
      crystal and other such defects.

PMID- 16089664
TI  - Investigation of nonlinear absorption processes with femtosecond light pulses in
      lithium niobate crystals.
AB  - The propagation of high-power femtosecond light pulses in lithium niobate
      crystals (LiNb O3 ) is investigated experimentally and theoretically in collinear
      pump-probe transmission experiments. It is found within a wide intensity range
      that a strong decrease of the pump transmission coefficient at wavelength 388 nm
      fully complies with the model of two-photon absorption; the corresponding
      nonlinear absorption coefficient is beta(p) approximately = 3.5 cm/GW.
      Furthermore, strong pump pulses induce a considerable absorption for the probe at
      776 nm. The dependence of the probe transmission coefficient on the time delay
      Delta t between probe and pump pulses is characterized by a narrow dip (at Delta
      t approximately = 0) and a long (on the picosecond time scale) lasting plateau.
      The dip is due to direct two-photon transitions involving pump and probe photons;
      the corresponding nonlinear absorption coefficient is beta(r) approximately = 0.9
      cm/GW. The plateau absorption is caused by the presence of pump-excited charge
      carriers; the effective absorption cross section at 776 nm is sigma(r)
      approximately = 8 x 10(-18) cm(2). The above nonlinear absorption parameters are
      not strongly polarization sensitive. No specific manifestations of the relaxation
      of hot carriers are found for a pulse duration of approximately = 0.24 ps.

PMID- 16089665
TI  - Determination of the diffusion constant using phase-sensitive measurements.
AB  - We apply a pulsed-light interferometer to measure both the intensity and the
      phase of light that is transmitted through a strongly scattering disordered
      material. From a single set of measurements we obtain the time-resolved
      intensity, frequency correlations and statistical phase information
      simultaneously. We compare several independent techniques of measuring the
      diffusion constant for diffuse propagation of light. By comparing these
      independent measurements, we obtain experimental proof of the consistency of the
      diffusion model and corroborate phase statistics theory.

PMID- 16089666
TI  - Vector-soliton collision dynamics in nonlinear optical fibers.
AB  - We consider the interactions of two identical, orthogonally polarized vector
      solitons in a nonlinear optical fiber with two polarization directions, described
      by a coupled pair of nonlinear Schrodinger equations. We study a low-dimensional
      model system of Hamiltonian ordinary differential equations (ODEs) derived by
      Ueda and Kath and also studied by Tan and Yang. We derive a further simplified
      model which has similar dynamics but is more amenable to analysis. Sufficiently
      fast solitons move by each other without much interaction, but below a critical
      velocity the solitons may be captured. In certain bands of initial velocities the
      solitons are initially captured, but separate after passing each other twice, a
      phenomenon known as the two-bounce or two-pass resonance. We derive an analytic
      formula for the critical velocity. Using matched asymptotic expansions for
      separatrix crossing, we determine the location of these "resonance windows."
      Numerical simulations of the ODE models show they compare quite well with the
      asymptotic theory.

PMID- 16089667
TI  - Modeling of defect modes in photonic crystals using the fictitious source
      superposition method.
AB  - We present an exact theory for modeling defect modes in two-dimensional photonic
      crystals having an infinite cladding. The method is based on three key concepts,
      namely, the use of fictitious sources to modify response fields that allow
      defects to be introduced, the representation of the defect mode field as a
      superposition of solutions of quasiperiodic field problems, and the
      simplification of the two-dimensional superposition to a more efficient, one
      dimensional average using Bloch mode methods. We demonstrate the accuracy and
      efficiency of the method, comparing results obtained using alternative
      techniques, and then concentrate on its strengths, particularly in handling
      difficult problems, such as where a mode is highly extended near cutoff, that
      cannot be dealt with in other ways.

PMID- 16089668
TI  - Ghost imaging with incoherent and partially coherent light radiation.
AB  - We theoretically study ghost imaging with incoherent and partially coherent light
      radiation by using classical optical coherence theory. A Gaussian thin lens
      equation is derived for the ghost image. The equation depends on both paths. The
      quality and visibility of the ghost image are influenced by the source's
      transverse size, coherence width, and object characteristics. The differences
      between ghost imaging formed with incoherent light radiation and with entangled
      photon pairs are discussed.

PMID- 16089669
TI  - Analytic properties of photonic crystal superprism parameters.
AB  - We study the analytic properties of the photonic crystal superprism resolution
      parameters p , q , and r introduced previously by Baba and Matsumoto [Appl. Phys.
      Lett. 81, 2325 (2002)], which characterize the potential dispersive power of a
      superprism. We find closed form expressions for these quantities that greatly
      simplify their accurate evaluation and reveal significant insights about their
      behavior. The expressions imply general properties of the parameters which are
      true for all bands and all photonic crystals. In particular, we demonstrate that
      all photonic crystals exhibit infinite resolution as measured by the parameter r
      along particular contours in any photonic band.

PMID- 16089670
TI  - Analysis of longitudinal-field reflection in dielectric gratings.
AB  - Because of a common approximation used in the derivation of the wave equation,
      conventional analyses of Bragg reflection from dielectric gratings do not account
      for the distinctive behavior of the longitudinal field component of the electric
      field. We address this issue, which has particular significance in subwavelength
      scale periodic dielectric structures. We discuss new reflection phenomena within
      the theoretical framework of coupled-wave analysis, supplemented with numerical
      calculations.

PMID- 16089671
TI  - Generalized optical theorem for reflection, transmission, and extinction of power
      for electromagnetic fields.
AB  - We present a generalization of the optical theorem for electromagnetic fields.
      This result is used to obtain the power extinguished from a field by a scatterer
      contained in a dielectric half space. Applications to microscopy and tomography
      are described.

PMID- 16089672
TI  - Equilibrium orientation of an ellipsoidal particle inside a dielectric medium
      with a finite electric conductivity in the external electric field.
AB  - We study the stability of the orientation of an ellipsoidal dielectric particle
      immersed into a host dielectric medium under the action of the external electric
      field. It is assumed that the particle and the host medium have a finite electric
      conductivity. We demonstrate that an equilibrium orientation of the ellipsoidal
      particle changes with time in a stationary electric field with a constant
      direction. It was found that during time interval T1 an equilibrium orientation
      of the spheroidal particle with a finite electric conductivity remains the same
      as the equilibrium orientation of an ideal dielectric particle. During time
      interval T2 , where T= T1 + T2 is a period of the external electric field, the
      equilibrium orientation of the axis of symmetry of the particle is normal to the
      initial equilibrium direction.

PMID- 16089673
TI  - Discrete quadratic cavity solitons.
AB  - We predict the existence of various types of discrete solitons in arrays of
      coupled optical cavities endowed with a quadratic nonlinearity. We derive mean
      field equations and determine their range of validity by comparing results with
      those from the original round-trip model. By using an analytical approach we
      identify domains in parameter space where solitons can potentially exist and
      describe their asymptotic behavior. Taking advantage of these results, we
      numerically find discrete solitons of different topologies. Some of them are
      unique to discrete models. Ultimately, we study the stability of these soliton
      solutions and find that discreteness appreciably influences this behavior.

PMID- 16089674
TI  - Polarization instability, steering, and switching of discrete vector solitons.
AB  - We study the dynamics of discrete vector solitons in arrays of weakly coupled
      birefringent optical waveguides with cubic nonlinear response. We start with a
      modulational instability analysis, followed by approximate analytical solutions
      in the form of strongly localized modes. Next, we compute the effective Peierls
      Nabarro potential for these modes and obtain the spatial average of the power
      transfer between both polarizations modes as a function of their relative phase.
      Finally, we combine the concepts of polarization mode instability with
      discreteness-induced beam trapping by the array, and demonstrate numerically the
      amplification of a weak signal by a strong pump of the other polarization,
      combined with simultaneous discretized all-optical switching.

PMID- 16089675
TI  - Squared-field amplitude modulus and radiation intensity nonequivalence within
      nonlinear slabs.
AB  - This paper presents an approach to wave propagation inside the Fabry-Perot
      framework. It states that the time-averaged Poynting vector modulus can be
      nonequivalent to the squared-field amplitude modulus. This fact permits the
      introduction of a kind of nonlinear medium whose nonlinearity is proportional to
      the time-averaged Poynting vector modulus. Its transmittance is calculated and
      found to differ from that obtained for a Kerr medium, whose nonlinearity is
      proportional to the squared-field amplitude modulus. The latter emphasizes the
      nonequivalence of these magnitudes. A space-time symmetry analysis shows that the
      Poynting nonlinearity should be possible only in noncentrosymmetric materials.

PMID- 16089676
TI  - Variational approach to spatial optical solitons in bulk cubic-quintic media
      stabilized by self-induced multiphoton ionization.
AB  - Propagation of an optical high-power cylindrically symmetric beam in a material
      characterized by cubic-quintic nonlinearity is studied both analytically and
      numerically. In this case we have to consider the self-defocusing effect caused
      by the presence of free electrons produced due to plasma formation. The
      variational method is used to study the system analytically. The finite
      difference beam propagation method is used for the numerical analysis. Stable
      (2+1) D spatial solitons are observed. The analytical results are found to be in
      very good agreement with the numerical results.

PMID- 16089677
TI  - Coupled-mode theory for spatial gap solitons in optically induced lattices.
AB  - We derive two systems of coupled-mode equations for spatial gap solitons in one
      dimensional (1D) and quasi-one-dimensional (Q1D) photonic lattices induced by two
      interfering optical beams in a nonlinear photorefractive crystal. The models
      differ from the ordinary coupled-mode system (e.g., for the fiber Bragg grating)
      by saturable nonlinearity and, if expanded to cubic terms, by the presence of
      four-wave-mixing terms. In the 1D system, solutions for stationary gap solitons
      are obtained in an implicit analytical form. For the Q1D model and for tilted
      ("moving") solitons in both models, solutions are found in a numerical form. The
      existence of stable tilted solitons in the full underlying model of the photonic
      lattice in the photorefractive medium is also shown. The stability of gap
      solitons is systematically investigated in direct simulations, revealing a
      nontrivial border of instability against oscillatory perturbations. In the Q1D
      model, two disjointed stability regions are found. The stability border of tilted
      solitons does not depend on the tilt. Interactions between stable tilted solitons
      are investigated too. The collisions are, chiefly, elastic, but they may be
      inelastic close to the instability border.

PMID- 16089678
TI  - Dynamic ultrasound radiation force in fluids.
AB  - The subject of this paper is to present a theory for the dynamic radiation force
      produced by dual-frequency ultrasound beams in lossless and nondispersive fluids.
      An integral formula for the dynamic radiation force exerted on a three
      dimensional object by a dual-frequency beam is obtained stemming from the fluid
      dynamics equations. The static radiation force due to a monochromatic wave
      appears as a particular case of this theory. Dependence of the dynamic radiation
      force to nonlinear effects of the medium is analyzed. We calculate the dynamic
      radiation force exerted on solid elastic spheres of two different materials by a
      low-amplitude dual-frequency plane wave. The static and dynamic radiation forces
      exhibited approximately same magnitude. Resonance patterns observed in the
      dynamic radiation force are similar to those present in the static radiation
      force.

PMID- 16089679
TI  - Measurement of dynamic and static radiation force on a sphere.
AB  - Dynamic radiation force from ultrasound has found increasing applications in
      elasticity imaging methods such as vibro-acoustography. Radiation force that has
      both static and dynamic components can be produced by interfering two ultrasound
      beams of slightly different frequencies. This paper presents a method to measure
      both static and dynamic components of the radiation force on a sphere suspended
      by thin threads in water. Due to ultrasound radiation force, the sphere deflects
      to an equilibrant position and vibrates around it. The static radiation force is
      estimated from the deflection of the sphere. The dynamic radiation force is
      estimated from the calculated radiation impedance of the sphere and its vibration
      speed measured by a laser vibrometer. Experimental results on spheres of
      different size, vibrated at various frequencies, confirm the theoretical
      prediction that the dynamic and static radiation force on a sphere have
      approximately equal magnitudes [G. T. Silva, Phys. Rev. E 71, 056617 (2005)].

PMID- 16089680
TI  - Exact solutions of the generalized nonlinear Schrodinger equation with
      distributed coefficients.
AB  - A broad class of exact self-similar solutions to the nonlinear Schrodinger
      equation (NLSE) with distributed dispersion, nonlinearity, and gain or loss has
      been found describing both periodic and solitary waves. Appropriate solitary wave
      solutions applying to propagation in optical fibers and optical fiber amplifiers
      with these distributed parameters have also been studied in detail. These
      solutions exist for physically realistic dispersion and nonlinearity profiles.
      They correspond either to compressing or spreading solitary pulses which maintain
      a linear chirp or to chirped oscillatory solutions. The stability of these
      solutions has been confirmed by numerical simulations of the NLSE with perturbed
      initial conditions. These self-similar propagation regimes are expected to find
      practical application in both optical fiber amplifier systems and in fiber
      compressors.

PMID- 16089681
TI  - Bistability in the sine-Gordon equation: the ideal switch.
AB  - The sine-Gordon equation, used as the representative nonlinear wave equation,
      presents a bistable behavior resulting from nonlinearity and generating
      hysteresis properties. We show that the process can be understood in a
      comprehensive analytical formulation and that it is a generic property of
      nonlinear systems possessing a natural band gap. The approach allows one to
      discover that the sine-Gordon equation can work as an ideal switch by reaching a
      transmissive regime with vanishing driving amplitude.

PMID- 16089682
TI  - Rotating photonic crystals: a medium for compact optical gyroscopes.
AB  - The effect of rotation of a photonic crystal that contains a set of microcavities
      is studied using the formulation of electrodynamics in rotating media. A new
      manifestation of the Sagnac effect is observed. It is shown that the phase shift
      or frequency difference between rotation-codirected and rotation-counterdirected
      propagations depends on a set of parameters not previously reported. The use of
      the new configuration for designing compact optical gyroscopes is studied and
      discussed.

PMID- 16089683
TI  - Reduced Maxwell-Duffing description of extremely short pulses in nonresonant
      media.
AB  - The propagation of extremely short pulses of an electromagnetic field
      (electromagnetic spikes) is considered in the framework of a model wherein the
      material medium is represented by anharmonic oscillators with cubic
      nonlinearities (Duffing model) and waves can propagate only in the right
      direction. The system of reduced Maxwell-Duffing equations admits two families of
      exact analytical solutions in the form of solitary waves. These are bright spikes
      propagating on a zero background, and bright and dark spikes propagating on a
      nonzero background. We find that these steady-state pulses are stable in terms of
      boundedness of the Hamiltonian. Direct simulations demonstrate that these pulses
      are very robust against perturbations. We find that a high-frequency modulated
      electromagnetic pulse evolves into a breather-like one. Conversely, a low
      frequency pulse transforms into a quasiharmonic wave.

PMID- 16089684
TI  - Capture into resonance in dynamics of a classical hydrogen atom in an oscillating
      electric field.
AB  - We consider a classical hydrogen atom in a linearly polarized electric field of
      slowly changing frequency. In the process of evolution, the system passes through
      resonances between the driving frequency and the Keplerian frequency of the
      electron's motion. At a resonance, a capture into the resonance can occur. After
      the capture, the system evolves in such a way that the resonance condition is
      approximately preserved, and parameters of the electron's orbit are varying. We
      study this phenomenon in the case of 2:1 resonance and show that the capture
      results in growth of the eccentricity of the electron's orbit. It strongly
      depends on the initial conditions, whether the capture occurs or not. Hence, the
      capture can be considered as a probabilistic phenomenon. The capture probability
      is defined and calculated.

PMID- 16089685
TI  - Scaling of non-Markovian Monte Carlo wave-function methods.
AB  - We demonstrate a scaling method for non-Markovian Monte Carlo wave-function
      simulations used to study open quantum systems weakly coupled to their
      environments. We derive a scaling equation, from which the result for the
      expectation values of arbitrary operators of interest can be calculated, all the
      quantities in the equation being easily obtainable from the scaled Monte Carlo
      wave-function simulations. In the optimal case, the scaling method can be used,
      within the weak coupling approximation, to reduce the size of the generated Monte
      Carlo ensemble by several orders of magnitude. Thus, the developed method allows
      faster simulations and makes it possible to solve the dynamics of the certain
      class of non-Markovian systems whose simulation would be otherwise too tedious
      because of the requirement for large computational resources.

PMID- 16089686
TI  - Diffusion properties of gradient-based lattice Boltzmann models of immiscible
      fluids.
AB  - We study the diffusion and phase separation properties of a gradient-based
      lattice Boltzmann model of immiscible fluids. We quantify problems of lattice
      pinning associated with the model, and suggest a scheme that removes these
      artifacts. The interface width is controlled by a single parameter that acts as
      an inverse diffusion length. We derive an analytic expression of a fully
      developed interfacial curve and show that interfaces evolve towards this stable
      distribution if no fluid is trapped. Fluid can become trapped inside a competing
      phase if no connecting path to the bulk phase exists. Such trapped bubbles also
      evolve towards the fully developed interfacial curve but constraints on mass
      conservation limit this development. We also show how small numerical errors lead
      to spontaneous phase separation for all values of the diffusion length.

PMID- 16089687
TI  - Forward symplectic integrators and the long-time phase error in periodic motions.
AB  - We show that when time-reversible symplectic algorithms are used to solve
      periodic motions, the energy error after one period is generally two orders
      higher than that of the algorithm. By use of correctable algorithms, we show that
      the phase error can also be eliminated two orders higher than that of the
      integrator. The use of fourth order forward time step integrators can result in
      sixth order accuracy for the phase error and eighth order accuracy in the
      periodic energy. We study the one-dimensional harmonic oscillator and the two
      dimensional Kepler problem in great detail, and compare the effectiveness of some
      recent fourth order algorithms.

PMID- 16089688
TI  - High-resolution numerical approximation of traffic flow problems with variable
      lanes and free-flow velocities.
AB  - This paper develops macroscopic traffic flow models for a highway section with
      variable lanes and free-flow velocities, that involve spatially varying flux
      functions. To address this complex physical property, we develop a Riemann solver
      that derives the exact flux values at the interface of the Riemann problem. Based
      on this solver, we formulate Godunov-type numerical schemes to solve the traffic
      flow models. Numerical examples that simulate the traffic flow around a
      bottleneck that arises from a drop in traffic capacity on the highway section are
      given to illustrate the efficiency of these schemes.

PMID- 16089689
TI  - Density of states of classical spin systems with continuous degrees of freedom.
AB  - In the last years different studies have revealed the usefulness of a
      microcanonical analysis of finite systems when dealing with phase transitions. In
      this approach the quantities of interest are exclusively expressed as derivatives
      of the entropy S=ln Omega where Omega is the density of states. Obviously, the
      density of states has to be known with very high accuracy for this kind of
      analysis. Important progress has been achieved recently in the computation of the
      density of states of classical systems, as new types of algorithms have been
      developed. Here we extend one of these methods, originally formulated for systems
      with discrete degrees of freedom, to systems with continuous degrees of freedom.
      As an application we compute the density of states of the three-dimensional XY
      model and demonstrate that critical quantities can directly be determined from
      the density of states of finite systems in cases where the degrees of freedom
      take continuous values.

PMID- 16089690
TI  - Lattice Boltzmann model for axisymmetric multiphase flows.
AB  - A lattice Boltzmann model is presented for axisymmetric multiphase flows. Source
      terms are added to a two-dimensional standard lattice Boltzmann equation for
      multiphase flows such that the emergent dynamics can be transformed into the
      axisymmetric cylindrical coordinate system. The source terms are temporally and
      spatially dependent and represent the axisymmetric contribution of the order
      parameter of fluid phases and inertial, viscous, and surface tension forces. A
      model which is effectively explicit and second order is obtained. This is
      achieved by taking into account the discrete lattice effects in the Chapman
      Enskog multiscale analysis, so that the macroscopic axisymmetric mass and
      momentum equations for multiphase flows are recovered self-consistently. The
      model is extended to incorporate reduced compressibility effects. Axisymmetric
      equilibrium drop formation and oscillations, breakup and formation of satellite
      droplets from viscous liquid cylindrical jets through Rayleigh capillary
      instability, and drop collisions are presented. Comparisons of the computed
      results with available data show satisfactory agreement.

PMID- 16089691
TI  - Newtonian fluid meets an elastic solid: coupling lattice Boltzmann and lattice
      spring models.
AB  - We integrate the lattice Boltzmann model (LBM) and lattice spring model (LSM) to
      capture the coupling between a compliant bounding surface and the hydrodynamic
      response of an enclosed fluid. We focus on an elastic, spherical shell filled
      with a Newtonian fluid where no-slip boundary conditions induce the interaction.
      We calculate the "breathing mode" oscillations for this system and find good
      agreement with analytical solutions. Furthermore, we simulate the impact of the
      fluid-filled, elastic shell on a hard wall and on an adhesive surface.
      Understanding the dynamics of fluid-filled shells, especially near adhesive
      surfaces, can be particularly important in the design of microcapsules for
      pharmaceutical and other technological applications. Our studies reveal that the
      binding of these capsules to specific surfaces can be sensitive to the physical
      properties of both the outer shell and the enclosed fluid. The integrated LBM-LSM
      methodology opens up the possibility of accurately and efficiently capturing the
      dynamic coupling between fluid flow and a compliant bounding surface in a broad
      variety of systems.

PMID- 16089692
TI  - Effects of data windows on the methods of surrogate data.
AB  - To generate surrogate data in nonlinear time series analysis, the Fourier
      transform is generally used. In the calculation of the Fourier transform, the
      time series is assumed to be periodic. Because such an assumption does not always
      hold true, the estimation accuracy of the Fourier transformed data and thus the
      power spectra is reduced. Due to such an estimation error, it is also possible
      that the surrogate test will lead to a false conclusion; for example, that a
      linear time series is nonlinear. In this paper, we experimentally evaluated the
      effects of data windows from the viewpoint of false rejections with several types
      of surrogate data. Our results indicate that if the data length becomes shorter,
      the false rejections by the data windows are reduced to a greater extent.
      However, if the data length is sufficient, the use of data windows is not a
      viable option. In the worst possible case wherein the linear memory of the
      original data is very long as in the nonstationary case, the critical length of
      the data for which the data windows were effective was approximately 1000.

PMID- 16089693
TI  - Simultaneous computation of free energies and kinetics of rare events.
AB  - We introduce a method to evaluate simultaneously the reaction rate constant and
      the free energy profile of a process in a complex environment. The method employs
      the partial path transition interface sampling technique we recently developed
      for the calculation of rate constants in diffusive systems. We illustrate the
      applicability of the technique by studying a simple dimer in a repulsive fluid,
      and show that the free energy can be obtained at no additional computational
      cost.

PMID- 16089694
TI  - Network clustering coefficient without degree-correlation biases.
AB  - The clustering coefficient quantifies how well connected are the neighbors of a
      vertex in a graph. In real networks it decreases with the vertex degree, which
      has been taken as a signature of the network hierarchical structure. Here we show
      that this signature of hierarchical structure is a consequence of degree
      correlation biases in the clustering coefficient definition. We introduce a
      definition in which the degree-correlation biases are filtered out, and provide
      evidence that in real networks the clustering coefficient is constant or decays
      logarithmically with vertex degree.

PMID- 16089695
TI  - Coevolutionary dynamics on scale-free networks.
AB  - We investigate Bak-Sneppen coevolution models on scale-free networks with various
      degree exponents gamma including random networks. For gamma>3 , the critical
      fitness value f(c) approaches a nonzero finite value in the limit N --> infinity,
      whereas f(c) approaches zero as 2<gamma< or =3. These results are explained by
      showing analytically f(c) (N) approximately =A/<(k+1)(2)>(N) on the networks with
      size N. The avalanche size distribution P (s) shows the normal power-law behavior
      for gamma>3. In contrast, P (s) for 2<gamma < or =3 has two power-law regimes.
      One is a short regime for small s with a large exponent tau(1) and the other is a
      long regime for large s with a small exponent tau(2) (tau(1) > tau(2) ). The
      origin of the two power regimes is explained by the dynamics on an artificially
      made star-linked network.

PMID- 16089696
TI  - Multiple dynamical resonances in a discrete neuronal model.
AB  - The conditions for the occurrence of different multiple resonances in an
      excitable neuron model are analyzed numerically. It is shown that the excitable
      system may display both stochastic and coherence resonance, in response to
      periodic stimuli in the presence of different intensities of additive and
      parametric noises. It is found that double coherence resonances may take place in
      the low-amplitude oscillation regimes, and coherence resonance may persists even
      in the weak oscillatory regimes for control parameters slightly larger than the
      Hopf bifurcation point, where the system is in the incipient stage of large
      amplitude excitation regime.

PMID- 16089697
TI  - Random walks on complex networks with inhomogeneous impact.
AB  - In many complex systems, for the activity f(i) of the constituents or nodes i a
      power-law relationship was discovered between the standard deviation sigma(i) and
      the average strength of the activity: sigma(i) proportional variant <f(i)>alpha:
      universal values alpha=1/2 or 1 were found, however, with exceptions. With the
      help of an impact variable we present a random walk model where the activity is
      the product of the number of visitors at a node and their impact. If the impact
      depends strongly on the node connectivity and the properties of the carrying
      network are broadly distributed (as in a scale-free network) we find both
      analytically and numerically nonuniversal alpha values. The exponent always
      crosses over to the universal value of 1 if the external drive dominates.

PMID- 16089698
TI  - Front propagation in hyperbolic fractional reaction-diffusion equations.
AB  - From the continuous-time random walk scheme and assuming a Levy waiting time
      distribution typical of subdiffusive transport processes, we study a hyperbolic
      reaction-diffusion equation involving time fractional derivatives. The linear
      speed selection of wave fronts in this equation is analyzed. When the reaction
      diffusion dimensionless number and the fractional index satisfy a certain
      condition, we find fronts exhibiting an unphysical behavior: they travel faster
      in the subdiffusive than in the diffusive regime.

PMID- 16089699
TI  - Synchronization in driven versus autonomous coupled chaotic maps.
AB  - The phenomenon of synchronization occurring in a locally coupled map lattice
      subject to an external drive is compared to the synchronization process in an
      autonomous coupled map system with similar local couplings plus a global
      interaction. It is shown that chaotic synchronized states in both systems are
      equivalent, but the collective states arising after the chaotic synchronized
      state becomes unstable can be different in these two systems. It is found that
      the external drive induces chaotic synchronization as well as synchronization of
      unstable periodic orbits of the local dynamics in the driven lattice. On the
      other hand, the addition of a global interaction in the autonomous system allows
      for chaotic synchronization which is not possible in a large coupled map system
      possessing only local couplings.

PMID- 16089700
TI  - Dangerous bifurcation at border collision: when does it occur?
AB  - It has been shown recently that border collision bifurcation in a piecewise
      smooth map can lead to a situation where a fixed point remains stable at both
      sides of the bifurcation point, and yet the orbit becomes unbounded at the point
      of bifurcation because the basin of attraction of the stable fixed point shrinks
      to zero size. Such bifurcations have been named "dangerous bifurcations." In this
      paper we provide explanation of this phenomenon, and develop the analytical
      conditions on the parameters under which such dangerous bifurcations will occur.

PMID- 16089701
TI  - Reexamination of Hagen-Poiseuille flow: shape dependence of the hydraulic
      resistance in microchannels.
AB  - We consider pressure-driven, steady-state Poiseuille flow in straight channels
      with various cross-sectional shapes: elliptic, rectangular, triangular, and
      harmonic-perturbed circles. A given shape is characterized by its perimeter P and
      area A which are combined into the dimensionless compactness number C= P2/A,
      while the hydraulic resistance is characterized by the well-known dimensionless
      geometrical correction factor alpha. We find that alpha depends linearly on C,
      which points out C as a single dimensionless measure characterizing flow
      properties as well as the strength and effectiveness of surface-related phenomena
      central to lab-on-a-chip applications. This measure also provides a simple way to
      evaluate the hydraulic resistance for the various shapes.

PMID- 16089702
TI  - Topology of plasma equilibria and the current closure condition.
AB  - A virtually complete description of the topology of stationary incompressible
      Euler flows and the magnetic field satisfying the magnetostatic equation is given
      by a theorem due to Arnol'd. We apply this theorem to describe the topology of
      stationary states of plasmas with significant fluid flow, obeying the Hall
      magnetohydrodynamics model equations. In the context of the integrability
      (nonchaotic topology) of the magnetic and velocity fields, we discuss the
      validity of conditions analogous to that of Greene and Johnson, which, in the
      case of magnetostatic equations, states that the line integral dl/B is the same
      for each closed magnetic field line on a given magnetic surface. We also show how
      this property follows from the existence of a continuous volume-preserving
      symmetry of the magnetic field.

PMID- 16089703
TI  - Stability of double-peaked solitons in Bragg gratings with the quadratic
      nonlinearity.
AB  - We report systematic results for the existence and stability of double-peaked
      (DP) solitons in the known model including the Bragg grating, which acts on the
      fundamental- and second-harmonic waves, and the quadratic (chi(2)) nonlinearity,
      which accounts for the parametric interaction between the harmonics. We identify
      existence and stability regions for the DP solitons in the plane of relevant
      parameters (the relative Bragg reflectivity at the two harmonics, and phase
      mismatch q between them). We conclude that the existence region considerably
      expands with the soliton's velocity v, while the stability area remains nearly
      constant up to a critical value of v. The stability region quickly vanishes as
      one crosses the critical value, while the region of the existence of unstable DP
      solitons does not disappear. The stability is confined to negative soliton
      frequencies, and almost entirely to q<0. Collisions between stable moving
      solitons are investigated too, with a conclusion that they are always
      destructive.

PMID- 16089704
TI  - Localization of light and second-order nonlinearity enhancement in weakly
      disordered one-dimensional photonic crystals.
AB  - We show how one-dimensional photonic crystal structures which suffer from a weak
      random disorder in the layer lengths may give rise to strong localization of
      light. Using the transfer matrix method we numerically study the effects of this
      localization in media with a second-order nonlinearity. Localization has a deep
      impact on the second-harmonic generation efficiency and may give rise to very
      strong enhancement in correspondence to the localized wavelengths.

PMID- 16089705
TI  - Phase-matched waveguide four-wave mixing scaled to higher peak powers with large
      core-area hollow photonic-crystal fibers.
AB  - Hollow photonic-crystal fibers with large core diameters are shown to allow
      waveguide nonlinear-optical interactions to be scaled to higher pulse peak
      powers. Phase-matched four-wave mixing is predicted theoretically and
      demonstrated experimentally for millijoule nanosecond pulses propagating in a
      hollow photonic-crystal fiber with a core diameter of about 50 microm ,
      suggesting the way to substantially enhance the efficiency of nonlinear-optical
      spectral transformations and wave mixing of high-power laser pulses in the gas
      phase.

PMID- 16089706
TI  - Maximum entropy and the problem of moments: a stable algorithm.
AB  - We present a technique for entropy optimization to calculate a distribution from
      its moments. The technique is based upon maximizing a discretized form of the
      Shannon entropy functional by mapping the problem onto a dual space where an
      optimal solution can be constructed iteratively. We demonstrate the performance
      and stability of our algorithm with several tests on numerically difficult
      functions. We then consider an electronic structure application, the electronic
      density of states of amorphous silica, and study the convergence of the Fermi
      level with increasing number of moments.

PMID- 16089707
TI  - Comment on "Soliton ratchets induced by excitation of internal modes".
AB  - Very recently Willis [Phys. Rev. E 69, 056612 (2004)] have used a collective
      variable theory to explain the appearance of a nonzero energy current in an ac
      driven, damped sine-Gordon equation. In this Comment, we prove rigorously that
      the time-averaged energy current in an ac-driven nonlinear Klein-Gordon system is
      strictly zero.

PMID- 16089709
TI  - Nonequilibrium fluctuations in a resistor.
AB  - In small systems where relevant energies are comparable to thermal agitation,
      fluctuations are of the order of average values. In systems in thermodynamical
      equilibrium, the variance of these fluctuations can be related to the dissipation
      constant in the system, exploiting the fluctuation-dissipation theorem. In
      nonequilibrium steady systems, fluctuations theorems (FT) additionally describe
      symmetry properties of the probability density functions (PDFs) of the
      fluctuations of injected and dissipated energies. We experimentally probe a model
      system: an electrical dipole driven out of equilibrium by a small constant
      current I, and show that FT are experimentally accessible and valid. Furthermore,
      we stress that FT can be used to measure the dissipated power P = R I2 in the
      system by just studying the PDFs' symmetries.

PMID- 16089710
TI  - Flux reversal in a two-state symmetric optical thermal ratchet.
AB  - A Brownian particle's random motions can be rectified by a periodic potential
      energy landscape that alternates between two states, even if both states are
      spatially symmetric. If the two states differ only by a discrete translation, the
      direction of the ratchet-driven current can be reversed by changing their
      relative durations. We experimentally demonstrate flux reversal in a symmetric
      two-state ratchet by tracking the motions of colloidal spheres moving through
      large arrays of discrete potential-energy wells created with dynamic holographic
      optical tweezers. The model's simplicity and high degree of symmetry suggest
      possible applications in molecular-scale motors.

PMID- 16089711
TI  - Molecular valves actuated by intermolecular forces.
AB  - Phase behavior in nanostructured thin films under a gradient in chemical
      potential is studied via kinetic Monte Carlo simulation. Switching between
      saturated, partially saturated, and unsaturated states drives precipitous changes
      in permeation. This phenomenon could render nanostructured thin films as
      molecular valves, where adsorbate-adsorbate forces actuate the flow of molecules.

PMID- 16089712
TI  - Jamming transition in two-dimensional hoppers and silos.
AB  - Jamming of monodisperse metal disks flowing through two-dimensional hoppers and
      silos is studied experimentally. Repeating the flow experiment M times in a
      hopper or silo (HS) of exit size d, we measure the histograms h(n) of the number
      of disks n through the HS before jamming. By treating the states of the HS as a
      Markov chain, we find that the jamming probability J(d), which is defined as the
      probability that jamming occurs in a HS containing m disks, is related to the
      distribution function F(n) is identical with (1/M) sigma(s=n) to (s=infinity)
      h(s) by J(d) = 1 - F(m) = 1 - e(-(alpha(m - n(o))). The decay rate alpha, as a
      function of d, is found to be the same for both hoppers and silos with different
      widths. The average number of disks N is identical with 1/alpha = [n] passing
      through the HS can be fitted to N = A e(Bd2), N = A e(B/(d(c) - d))), or N = A
      (d(c) - d)(-gamma). The implications of these three forms for N to the stability
      of dense flow are discussed.

PMID- 16089713
TI  - Nearly logarithmic decay in the colloidal hard-sphere system.
AB  - Nearly logarithmic decay is identified in the data for the mean-squared
      displacement of the colloidal hard-sphere system at the liquid-glass transition
      [W. van Megen, Phys. Rev. E 58, 6073 (1998)]. The solutions of the mode-coupling
      theory for the microscopic equations of motion fit the experimental data well.
      Based on these equations, the nearly logarithmic decay is explained as the
      equivalent of a beta-peak phenomenon, a manifestation of the critical relaxation
      when the coupling between of the probe variable and the density fluctuations is
      strong. In an asymptotic expansion, a Cole-Cole formula including corrections is
      derived from the microscopic equations of motion, which describes the
      experimental data for three decades in time.

PMID- 16089714
TI  - Equilibrium bundle size of rodlike polyelectrolytes with counterion-induced
      attractive interactions.
AB  - Multivalent counterions can induce an effective attraction between like-charged
      rodlike polyelectrolytes, leading to the formation of polyelectrolyte bundles. In
      this paper, we calculate the equilibrium bundle size using a simple model in
      which the attraction between polyelectrolytes (assumed to be pairwise additive)
      is treated phenomenologically. If the counterions are pointlike, they almost
      completely neutralize the charge of the bundle, and the equilibrium bundle size
      diverges. When the counterions are large, however, steric and short-range
      electrostatic interactions prevent charge neutralization of the bundle, thus
      forcing the equilibrium bundle size to be finite. We also show that if the
      attractive interactions between the rods become frustrated as the bundle grows,
      finite-size bundles can be obtained with pointlike counterions.

PMID- 16089715
TI  - Conformational properties of an adsorbed charged polymer.
AB  - The behavior of a strongly charged polymer adsorbed on an oppositely charged
      surface of a low-dielectric constant is formulated by the functional integral
      method. By separating the translational, conformational, and fluctuational
      degrees of freedom, the scaling behaviors for both the height of the polymer and
      the thickness of the diffusion layer are determined. Unlike the results predicted
      by scaling theory, we identified the continuous crossover from the weak
      compression to the compression regime. All the analytical results are found to be
      consistent with Monte Carlo simulations. Finally, an alternative (operational)
      definition of a charged polymer adsorption is proposed.

PMID- 16089716
TI  - Negative superdiffusion due to inhomogeneous convection.
AB  - Fractional transport of particles on a comb structure in the presence of an
      inhomogeneous convection flow is studied [Baskin and Iomin, Phys. Rev. Lett. 93,
      120603 (2004)]. The large scale asymptotics is considered. It is shown that a
      contaminant spreads superdiffusively in the direction opposite to the convection
      flow. Conditions for the realization of this effect are discussed in detail.

PMID- 16089717
TI  - Isothermal stress and elasticity tensors for ions and point dipoles using Ewald
      summations.
AB  - The isothermal stress tensor and isothermal elasticity tensor for systems of
      point charges and of nonpolarizable point dipoles are derived from the strain
      derivatives of the free energy. For the case of point dipoles, it is shown that
      the angular dependence of the interaction potential gives rise to additional
      contributions to the stress and elasticity tensors not recognized previously.

PMID- 16089718
TI  - Relaxation to equilibrium in few-particle adiabatic piston systems.
AB  - A Hamiltonian system with few particles and a heavy adiabatic piston is studied.
      With ensemble averages based on proper classification of slow and fast variables,
      a nonequilibrium state is defined and the relaxation from nonequilibrium to
      equilibrium is investigated. Coherent oscillation, dissipative oscillation
      damping, and anti-intuition energy transfer of the adiabatic piston are observed
      by numerical simulations. Noise-driven thermodynamic equations of slow variables
      are derived, based on the assumption of local equilibrium and the fluctuation
      dissipation theorem, to understand and quantitatively reproduce all the above few
      body nonequilibrium relaxation features.

PMID- 16089719
TI  - Analytically solvable model in fractional kinetic theory.
AB  - In this article we give a general prescription for incorporating memory effects
      in phase space kinetic equation, and consider in particular the generalized
      "fractional" relaxation time model equation. We solve this for small-signal
      charge carriers undergoing scattering, trapping, and detrapping in a time-of
      flight experimental arrangement in two ways: (i) approximately via the Chapman
      Enskog scheme for the weak gradient, hydrodynamic regime, from which the
      fractional form of Fick's law and diffusion equation follow; and (ii) exactly,
      without any limitations on gradients. The latter yields complete and exact
      expressions in terms of generalized Mittag-Lefler functions for experimentally
      observable quantities. These expressions enable us to examine in detail the
      transition from the nonhydrodynamic stage to the hydrodynamic regime, and thereby
      establish the limits of validity of Fick's law and the corresponding fractional
      diffusion equation.

PMID- 16089720
TI  - Subdiffusion in random compressible flows.
AB  - In this work, we study the diffusion of admixture particles in a one-dimensional
      velocity field given by a gradient of a random potential. This refers us to the
      case of random compressible flows, where previously only scaling estimates were
      available. We develop a general approach which allows to solve this problem
      analytically. With its help we derive the macroscopic transport equation and
      rigorously show in which cases transport can be subdiffusive. We find the Fourier
      Laplace transform of the Green's function of this equation and prove that for
      some potential distributions it satisfies the subdiffusive equation with
      fractional derivative with respect to time.

PMID- 16089721
TI  - Incorporation of excluded-volume correlations into Poisson-Boltzmann theory.
AB  - We investigate the effect of excluded-volume interactions on the electrolyte
      distribution around a charged macroion. First, we introduce a criterion for
      determining when hard-core effects should be taken into account beyond standard
      mean-field Poisson-Boltzmann (PB) theory. Next, we demonstrate that several
      commonly proposed local-density-functional approaches for excluded-volume
      interactions cannot be used for this purpose. Instead, we employ a nonlocal
      excess free energy by using a simple constant-weight approach. We compare the ion
      distribution and osmotic pressure predicted by this theory with Monte Carlo
      simulations. They agree very well for weakly developed correlations and give the
      correct layering effect for stronger ones. In all investigated cases our simple
      weighted-density theory yields more realistic results than the standard PB
      approach, whereas all local density theories do not improve on the PB density
      profiles, but on the contrary, deviate even more from the simulation results.

PMID- 16089722
TI  - Anomalous time correlation in two-dimensional driven diffusive systems.
AB  - We study the time-correlation function of a density field in two-dimensional
      driven diffusive systems within the framework of fluctuating hydrodynamics. It is
      found that the time correlation exhibits power-law behavior in an intermediate
      time regime in the case that the fluctuation-dissipation relation is violated and
      that the power-law exponent depends on the extent of this violation. We obtain
      this result by employing a renormalization group method to treat a logarithmic
      divergence in time.

PMID- 16089723
TI  - Elastically coupled two-dimensional Brownian motors.
AB  - Many workers have theoretically and numerically studied Brownian motors (ratchet
      models) as models for molecular motors for many years. Their studies have been
      mainly concerned about one-dimensional motion of a particle or coupled particles
      experiencing spatially asymmetric interaction force. In this paper, we introduce
      a coupled flashing ratchet model, that is, elastically coupled Brownian particles
      with their own easily advancing directions under the on-and-off (or occasional)
      influence of two-dimensional interaction force asymmetric in the easily advancing
      direction of each particle. The dynamics of the model is investigated by computer
      simulation and characteristic motion of the particles in the two-dimensional
      space is observed. Our model is also studied as that for molecular motors in
      muscle contraction and the simulation results are compared with those of in vitro
      biological experiments in motility assays of the molecular motors. We succeed in
      reproducing the experimental results qualitatively with our model.

PMID- 16089724
TI  - Domain growth in Ising systems with quenched disorder.
AB  - We present results from extensive Monte Carlo (MC) simulations of domain growth
      in ferromagnets and binary mixtures with quenched disorder. These are modeled by
      the random-bond Ising model and the dilute Ising model with either nonconserved
      (Glauber) spin-flip kinetics or conserved (Kawasaki) spin-exchange kinetics. In
      all cases, our MC results are consistent with power-law growth with an exponent
      theta(T, epsilon) which depends on the quench temperature T and the disorder
      amplitude epsilon. Such exponents arise naturally when the coarsening domains are
      trapped by energy barriers that grow logarithmically with the domain size. Our MC
      results show excellent agreement with the predicted dependence of theta(T,
      epsilon).

PMID- 16089725
TI  - Linear response theory for thermal conductivity and viscosity in terms of
      boundary fluctuations.
AB  - Boundary driven shear flows and wall thermostats are being used in computer
      simulations of materials with increasing frequency. One attraction is that such
      boundary constraints offer a more realistic representation of the physical
      constraints imposed experimentally than the widely employed homogeneous
      constraints. In this paper we derive the linear response expressions for shear
      viscosity and thermal conductivity based on the fluctuations associated with
      boundary constraints. We demonstrate that our approach provides an effective
      method of describing the rheology in interfaces as well as bulk samples.

PMID- 16089726
TI  - Role of chaos in one-dimensional heat conductivity.
AB  - We investigate the heat conduction in a quasi-one-dimensional gas model with
      various degrees of chaos. Our calculations indicate that the heat conductivity
      kappa is independent of system size when the chaos of the channel is strong
      enough. The different diffusion behaviors for the cases of chaotic and nonchaotic
      channels are also studied. The numerical results of divergent exponent alpha of
      heat conduction and diffusion exponent beta are consistent with the formula alpha
      = 2 - 2/beta. We explore the temperature profiles numerically and analytically,
      which show that the temperature jump is primarily attributed to superdiffusion
      for both nonchaotic and chaotic cases, and for the latter case of superdiffusion
      the finite size affects the value of beta remarkably.

PMID- 16089727
TI  - Computer simulations of the structure of colloidal ferrofluids.
AB  - The structure of a ferrofluid under the influence of an external magnetic field
      is expected to become anisotropic due to the alignment of the dipoles into the
      direction of the external field, and subsequently to the formation of particle
      chains due to the attractive head to tail orientations of the ferrofluid
      particles. Knowledge about the structure of a colloidal ferrofluid can be
      inferred from scattering data via the measurement of structure factors. We have
      used molecular-dynamics simulations to investigate the structure of both
      monodispersed and polydispersed ferrofluids. The results for the isotropic
      structure factor for monodispersed samples are similar to previous data by Camp
      and Patey that were obtained using an alternative Monte Carlo simulation
      technique, but in a different parameter region. Here we look in addition at
      bidispersed samples and compute the anisotropic structure factor by projecting
      the q vector onto the XY and XZ planes separately, when the magnetic field was
      applied along the z axis. We observe that the XY-plane structure factor as well
      as the pair distribution functions are quite different from those obtained for
      the XZ plane. Further, the two-dimensional structure factor patterns are
      investigated for both monodispersed and bidispersed samples under different
      conditions. In addition, we look at the scaling exponents of structure factors.
      Our results should be of value to interpret scattering data on ferrofluids
      obtained under the influence of an external field.

PMID- 16089728
TI  - Memory function for a fluid of molecules interacting through steeply repulsive
      potentials.
AB  - Previous studies of the properties of fluids of molecules interacting through
      steeply repulsive central potentials are extended to the investigation of the
      memory function. It is assumed that collisions are dominated by binary collisions
      and a general formula previously derived by Miyazaki, Srinivas, and Bagchi [J.
      Chem. Phys. 114, 6276 (2001)] is applied to the present problem. It is shown that
      the equations of motion of a pair of molecules can be solved explicitly and
      substitution of the result into the formula leads to a closed explicit expression
      for the memory function which is easily evaluated for any given state. In the
      limit of hard spheres this result leads to Enskog's equation and represents a
      generalization of that formula to fluids with softer potentials. The results
      obtained from the formula are compared with those derived from the molecular
      dynamics simulation. The velocity autocorrelation function was calculated using
      the generalized soft sphere potential, phi(r) = epsilon (sigma/r)(n), where
      epsilon and sigma set the energy and size of the molecule, and the exponent, n,
      is a variable. The two approaches agree very well for a range of state points for
      n large, especially at short times.

PMID- 16089729
TI  - Convection in vibrated annular granular beds.
AB  - The response to vibration of a granular bed, consisting of a standard cylindrical
      geometry but with the addition of a dissipative cylindrical inner wall, has been
      investigated both experimentally (using positron emission particle tracking) and
      numerically (using hard sphere molecular dynamics simulation). The packing
      fraction profiles and granular temperature distributions (in both vertical and
      horizontal directions) were determined as a function of height and distance from
      the axis. The two sets of results were in reasonable agreement. The molecular
      dynamics simulations were used to explore the behavior of the granular bed in the
      inner wall-outer wall coefficient of restitution phase space. It was observed
      that one could control the direction of the toroidal convection rolls by
      manipulating the relative dissipation at the inner and outer walls via the
      coefficients of restitution, and with several layers of grains it was seen that
      double convection rolls could also be formed, a result that was subsequently
      confirmed experimentally.

PMID- 16089730
TI  - Geometrical structure of disordered sphere packings.
AB  - The three-dimensional structure of large packings of monosized spheres with
      volume fractions ranging between 0.58 and 0.64 has been studied with x-ray
      computed tomography. We search for signatures of organization, classifying local
      arrangements and exploring the effects of local geometrical constrains on the
      global packing. This study is the largest and the most accurate empirical
      analysis of disordered packings at the grain-scale to date, mapping over 380,000
      sphere coordinates with precision within 0.1% of the sphere diameters. We discuss
      topological and geometrical methods to characterize and classify these systems
      emphasizing the implications that local geometry can have on the mechanisms of
      formation of these amorphous structures. Some of the main results are (1) the
      observation that the average number of contacts increases with the volume
      fraction; (2) the discovery that these systems have a very compact contact
      network; (3) the finding that disordered packing can be locally more efficient
      than crystalline packings; (4) the observation that the peaks of the radial
      distribution function follow power law divergences; (5) the discovery that
      geometrical frustration plays no role in the formation of such amorphous
      packings.

PMID- 16089731
TI  - Piling and avalanches of magnetized particles.
AB  - We performed computer simulations based on a two-dimensional distinct element
      method to study granular systems of magnetized spherical particles. We measured
      the angle of repose and the surface roughness of particle piles, and we studied
      the effect of magnetization on avalanching. We report linear dependence of both
      angle of repose and surface roughness on the ratio f of the magnetic dipole
      interaction and the gravitational force (interparticle force ratio). There is a
      difference in avalanche formation at small and at large interparticle force
      ratios. The transition is at f(c) approximately 7. For f < f(c) small vertical
      chains follow each other at short times (granular regime), while for f > f(c) the
      avalanches are typically formed by one single large particle-cluster (correlated
      regime). The transition is not sharp. We give plausible estimates for f(c) based
      on stability criteria.

PMID- 16089732
TI  - Slow drag in polydisperse granular mixtures under high pressure.
AB  - The behavior of polydisperse granular materials, composed of mixtures of
      particles of different sizes, is studied under conditions of high pressure and
      confinement. Two types of experiments are performed. In the first type, granular
      mixtures are compressed, with the resulting force-displacement curve used to
      calculate density and volume modulus. In the second set of experiments, the drag
      force is measured by pulling a cylinder, horizontally, through a compressed
      granular mixture. The density, volume modulus, and drag forces for the mixtures
      are quantified in terms of the mixture composition. The results show that the
      behavior of these mixtures depends strongly on the mass fractions of the
      different sized particles, with density, volume modulus, and drag force all
      reaching values significantly higher than observed in the monodisperse granular
      materials. Furthermore, the trends for density and drag force show strong
      correlation, suggesting that drag resistance of confined granular media could be
      directly related to packing effects. These results should prove useful in
      understanding the physics of drag in granular materials under high pressure, such
      as ballistic penetration of soils or ceramic armors.

PMID- 16089733
TI  - Jamming transition in granular media: a mean-field approximation and numerical
      simulations.
AB  - In order to study analytically the nature of the jamming transition in granular
      material, we have considered a cavity method mean-field theory, in the framework
      of a statistical mechanics approach, based on Edwards' original idea. For
      simplicity, we have applied the theory to a lattice model, and a transition with
      exactly the same nature of the glass transition in mean-field models for usual
      glass formers is found. The model is also simulated in three dimensions under tap
      dynamics, and a jamming transition with glassy features is observed. In
      particular, two-step decays appear in the relaxation functions and dynamic
      heterogeneities resembling ones usually observed in glassy systems. These results
      confirm early speculations about the connection between the jamming transition in
      granular media and the glass transition in usual glass formers, giving moreover a
      precise interpretation of its nature.

PMID- 16089734
TI  - Random close packing revisited: ways to pack frictionless disks.
AB  - We create collectively jammed (CJ) packings of 50-50 bidisperse mixtures of
      smooth disks in two dimensions (2D) using an algorithm in which we successively
      compress or expand soft particles and minimize the total energy at each step
      until the particles are just at contact. We focus on small systems in 2D and thus
      are able to find nearly all of the collectively jammed states at each system
      size. We decompose the probability P(phi) for obtaining a collectively jammed
      state at a particular packing fraction phi into two composite functions: (1) the
      density of CJ packing fractions rho(phi), which only depends on geometry, and (2)
      the frequency distribution beta(phi), which depends on the particular algorithm
      used to create them. We find that the function rho(phi) is sharply peaked and
      that beta(phi) depends exponentially on phi. We predict that in the infinite
      system-size limit the behavior of P(phi) in these systems is controlled by the
      density of CJ packing fractions--not the frequency distribution. These results
      suggest that the location of the peak in P(phi) when N --> infinity can be used
      as a protocol-independent definition of random close packing.

PMID- 16089735
TI  - Stress results from two-dimensional granular shear flow simulations using various
      collision models.
AB  - Collision resolution is one of the key elements in a discrete element method
      algorithm for modeling granular flows. Several collision models have been
      proposed for this process. The hard-particle collision approach is typically used
      for dilute systems, or for those in which the assumption of binary and
      instantaneous particle-particle contact remains valid. As the solids fraction
      increases, however, multiple, enduring collisions can occur and a soft-particle
      approach is more appropriate for resolving the collision dynamics. In this work,
      the delineation between dilute and dense systems and the suitability of contact
      models are explored for a range of solid fractions. Stress results for two
      dimensional shear flow simulations are compared using several collision models
      including an event-driven hard-particle model, a hysteretic spring soft-particle
      collision model following Walton and Braun [J. Rheol. 30, 949 (1986)], and a
      hybrid hard-particle-with-overlap model following Hopkins and Louge [Phys. Fluids
      A 3, 47 (1991)]. Results show that stresses are accurately predicted for a range
      of solids fractions, coefficients of restitution, and friction coefficients by
      both the hard-particle-with-overlap and soft-particle models so long as a
      sufficiently large loading stiffness is used for the soft-particle model.
      Additional results investigating the accuracy of the collision models and the
      amount of collisional overlap are presented as functions of the simulation time
      step and model parameters.

PMID- 16089736
TI  - Comparison between step strains and slow steady shear in a bubble raft.
AB  - We report on a comparison between stress relaxations after an applied step strain
      and stress relaxations during slow, continuous strain in a bubble raft. A bubble
      raft serves as a model two-dimensional foam and consists of a single layer of
      bubbles on a water surface. For both step strains and continuous strain, one
      observes periods of stress increase and decrease. Our focus is on the
      distribution of stress decreases, or stress drops. The work is motivated by
      apparent disagreements between quasistatic simulations of flowing foam and
      simulations of continuous strain for foam. Quasistatic simulations have reported
      larger average stress drops than the continuous strain case. Also, there is
      evidence in quasistatic simulations for a general divergence of the average size
      of the stress drops that only appears to occur in steady strain near special
      values of the foam density. In this work, applied step strains are used as an
      approximation to quasistatic simulations. We find general agreement in the
      dependence of the average stress drop on rate of strain, but we do not observe
      evidence for a divergence of the average stress drop.

PMID- 16089737
TI  - Correlation of fragility of supercooled liquids with elastic properties of
      glasses.
AB  - We present a detailed analysis of correlations between fragility and other
      parameters of glass-forming systems. The analysis shows the importance of the
      ratio between the instantaneous bulk and shear modulus of glass-forming systems,
      or their Poisson ratio, for structural alpha relaxation and fast dynamics. In
      particular, for simple glass formers, the bulk to shear modulus ratio in the
      glassy state correlates with fragility in the liquid state and is inversely
      proportional to the intensity of the boson peak. A simple relationship between
      the temperature dependence of the viscosity of liquids at high temperatures and
      near the glass transition is used to rationalize these correlations. We argue
      that the ratio of the moduli controls the high-temperature activation energy of
      the structural relaxation and in this way affects the fragility. The ratio also
      defines the amplitude of the structural relaxation (i.e., the nonergodicity
      parameter) and the latter influences the strength of the boson peak. These
      observations might explain the puzzling correlation observed between the
      fragility and fast dynamics in glass-forming systems.

PMID- 16089738
TI  - Translational dynamics of water in the nanochannels of oriented chrysotile
      asbestos fibers.
AB  - We performed a high-resolution quasielastic neutron scattering study of water
      dynamics in fully hydrated oriented chrysotile asbestos [chemical formula
      Mg3Si2O5(OH)4] fibers. The fibers possess sets of macroscopically long, parallel
      channels with a characteristic diameter of about 5 nm. Freezing of water in the
      channels was observed at about 237 K. Measurements at 280, 260, and 240 K
      revealed a translational dynamics of water molecules with the relaxation time
      slower by more than an order of magnitude compared to bulk water. The Q
      dependence of the quasielastic broadening was typical of a translational
      diffusion motion with a distribution of jump lengths, similar to that observed in
      bulk water. The relaxation time showed no significant anisotropy in the
      measurements with the scattering vector parallel and perpendicular to the fiber
      axes.

PMID- 16089739
TI  - Shear alignments in three-dimensional simulations of lamellar phases.
AB  - Experiments studying layer orientation of sheared lamellar phases have
      consistently observed not only the seemingly obvious parallel orientation (with
      layers parallel to the shear plane), but also the so called perpendicular
      orientation (with layer normals along the vorticity direction) at the condition
      of higher shear frequencies and near the lamellar phase transition. We find that
      three-dimensional simulations of a deterministic mesoscopic dynamical equation
      (without thermal fluctuations) under the convection of simple shear flows have
      shown exactly such a dependence. The simulations show the important role played
      by the transverse orientation (layer normal along the velocity direction) and
      highlight the mechanism of the shear alignment being the competition between the
      shear frequency and the mesoscopic time scale of pattern organization.

PMID- 16089740
TI  - Liquid-liquid phase transition for an attractive isotropic potential with wide
      repulsive range.
AB  - We investigate how the phase diagram of a repulsive soft-core attractive
      potential, with a liquid-liquid phase transition in addition to the standard gas
      liquid phase transition, changes by varying the parameters of the potential. We
      extend our previous work on short soft-core ranges to the case of large soft-core
      ranges, by using an integral equation approach in the hypernetted-chain
      approximation. We show, using a modified van der Waals equation we recently
      introduced, that if there is a balance between the attractive and repulsive part
      of the potential this potential has two fluid-fluid critical points well
      separated in temperature and in density. This implies that for the repulsive
      (attractive) energy U(R)(U(A)) and the repulsive (attractive) range w(R)(w(A))
      the relation U(R)/U(A) proportional to w(R)/w(A) holds for short soft-core
      ranges, while U(R)/U(A) proportional to 3w(R)/w(A) holds for large soft-core
      ranges.

PMID- 16089741
TI  - Structural order in glassy water.
AB  - We investigate structural order in glassy water by performing classical molecular
      dynamics simulations using the extended simple point charge (SPC/E) model of
      water. We perform isochoric cooling simulations across the glass transition
      temperature at different cooling rates and densities. We quantify structural
      order by orientational and translational order metrics. Upon cooling the liquid
      into the glassy state, both the orientational order parameter Q and translational
      order parameter tau increase. At T=0 K, the glasses fall on a line in the Q-tau
      plane or order map. The position of this line depends only on density and
      coincides with the location in the order map of the inherent structures (IS)
      sampled upon cooling. We evaluate the energy of the IS, eIS(T), and find that
      both order parameters for the IS are proportional to eIS. We also study the
      structural order during the transformation of low-density amorphous ice (LDA) to
      high-density amorphous ice (HDA) upon isothermal compression and are able to
      identify distinct regions in the order map corresponding to these glasses.
      Comparison of the order parameters for LDA and HDA with those obtained upon
      isochoric cooling indicates major structural differences between glasses obtained
      by cooling and glasses obtained by compression. These structural differences are
      only weakly reflected in the pair correlation function. We also characterize the
      evolution of structural order upon isobaric annealing, leading at high pressure
      to very-high density amorphous ice (VHDA).

PMID- 16089742
TI  - Critical exponents of the driven elastic string in a disordered medium.
AB  - We analyze the harmonic elastic string driven through a continuous random
      potential above the depinning threshold. The velocity exponent beta = 0.33(2) is
      calculated. We observe a crossover in the roughness exponent zeta from the
      critical value 1.26 to the asymptotic (large force) value of 0.5. We calculate
      directly the velocity correlation function and the corresponding correlation
      length exponent nu = 1.29(5), which obeys the scaling relation nu = 1/(2 - zeta),
      and agrees with nu(FS), the finite-size-scaling exponent of fluctuations in the
      critical force. Surprisingly, the velocity correlation function is nonuniversal
      at short distances.

PMID- 16089743
TI  - Critical behavior of the banded-unbanded spherulite transition in a mixture of
      ethylene carbonate with polyacrylonitrile.
AB  - We investigate the transition from unbanded to banded spherulitic growth in
      mixtures of ethylene carbonate with polyacrylonitrile. By carefully considering
      systematic errors, we show that the band spacing diverges with a power-law form
      showing scaling over nearly two decades. We also observe that the bands disorder
      as the transition point is approached. The critical exponent is nonclassical. One
      possible explanation is that the nonequilibrium transition is actually weakly
      first order (subcritical).

PMID- 16089744
TI  - Sharp-interface projection of a fluctuating phase-field model.
AB  - We present a derivation of the sharp-interface limit of a generic fluctuating
      phase-field model for solidification. As a main result, we obtain a sharp
      interface projection which presents noise terms in both the diffusion equation
      and in the moving boundary conditions. The presented procedure does not rely on
      the fluctuation-dissipation theorem, and can therefore be applied to account for
      both internal and external fluctuations in either variational or nonvariational
      phase-field formulations. In particular, it can be used to introduce
      thermodynamical fluctuations in nonvariational formulations of the phase-field
      model, which permit to reach better computational efficiency and provide more
      flexibility for describing some features of specific physical situations. This
      opens the possibility of performing quantitative phase-field simulations in
      crystal growth while accounting for the proper fluctuations of the system.

PMID- 16089745
TI  - Cell dynamics approach to the formation of metastable phases during phase
      transformation.
AB  - In this paper, we use the cell dynamics method to study the dynamics of phase
      transformation when three phases exist. The system we study is a two-dimensional
      system. The system is able to achieve three phases coexistence, which for
      simplicity we call crystal, liquid and vapor phases. We focus our study on the
      case when the vapor and crystal phases are stable and can coexist while the other
      intermediate liquid phase is metastable. In this study we examine the most
      fundamental process of the growth of a composite nucleus which consists of a
      circular core of one phase surrounded by a circular layer of second phase
      embedded in a third phase. We found that there is one special configuration that
      consists of a core stable phase surrounded by another stable phase in a
      metastable liquid environment which becomes stationary and stable. Then, the
      nucleus does not grow and the metastable liquid survives. The macroscopic liquid
      phase does not disappear even though it is thermodynamically metastable. This
      result seems compatible to the argument of kinetics of phase transition developed
      by Cahn [J. Am. Ceram. Soc. 52, 118 (1969)] based on the construction of a common
      tangent of the free energy curve.

PMID- 16089746
TI  - Terahertz spectroscopy in smectic phases of a bent-core molecule.
AB  - The dynamics of a bent-core molecule in two smectic phases is studied using
      terahertz (THz) spectroscopy, which enables us to observe some rapid molecular
      motions and segmental motions reflecting intermolecular interactions. The
      isotropic liquid, liquid crystal and crystal phases of the bent-core liquid
      crystal P-8-PIMB are clearly distinguished by THz spectra. Unexpectedly, the
      transmittance in the B3 phase, which has been assigned to either a highly ordered
      smectic or crystal phase from results of x-ray diffraction analysis, is almost
      the same as that in the switchable liquid-crystalline B2 phase. This suggests
      that the molecular dynamics in the B3 phase is liquid-crystal-like on this time
      scale.

PMID- 16089747
TI  - Low-voltage-driven electromechanical effects of swollen liquid-crystal
      elastomers.
AB  - We experimentally investigate, in detail, electromechanical effects in liquid
      crystal elastomers (LCEs) previously swollen with low-molecular-weight liquid
      crystals (LMWLCs). Both polydomain (POLY) and monodomain (MONO) LCEs were
      studied. We used a well known LMWLC, 4-n-pentyl-4-cyanobiphenyl (5CB) as a
      solvent. After swelling POLY and MONO LCEs (LSCE) with 5CB, shape changes were
      measured by recording the displacement of the edge of the swollen LCE at
      different voltages, V, and temperature. With 100 microm distance between
      electrodes, measurable shape changes (approximately 1-20 microm) are observed
      with small voltages (V approximately 0.5-10 V). In particular, we note that,
      compared to unswollen L(S)CEs, a dramatic approximately 200 times decrease of the
      threshold field was found for electromechanical effects in swollen L(S)CEs. While
      swollen MONO LCEs showed electromechanical effects in the planar geometry,
      homeotropic MONO swollen with homeotropically oriented 5CB did not. This is easy
      to understand because, in the homeotropic case, the liquid-crystal preferred axis
      is already aligned with the field so the field has no reorienting effect. The
      inverse of the response time when the field was switched on in both POLY and MONO
      was proportional to E2, which is the same field dependence as the response time
      of LMWLCs. When the field was switched off, the relaxation time showed a field
      dependence different from that of LMWLCs that we attribute to relaxation of the
      LCE network.

PMID- 16089748
TI  - Tricritical points in biaxial liquid crystal phases.
AB  - We further pursue the analysis of a mean-field model recently proposed by Sonnet
      [Phys. Rev. E 67, 061701 (2003)] to describe nematic biaxial phases. This model,
      which is based on a simplified version of Straley's pair potential, is
      characterized by the prediction of a tricritical point along the transition line
      between uniaxial and biaxial phases. We show that the same model predicts another
      tricritical point, but along the line of the direct isotropic-to-biaxial
      transition. Our prediction is quantitative, as it stems from an analytical
      criterion for tricriticality.

PMID- 16089749
TI  - Anomalous heat capacity above the isotropic-chiral-smectic-C phase transition.
AB  - A phenomenological model is developed to describe the isotropic-chiral-smectic-C
      phase transition. The anomalous part of the heat capacity of the chiral-smectic-C
      liquid crystals above the isotropic-chiral-smectic-C phase transition is
      calculated using Landau's fluctuation theory. The temperature dependence of the
      heat capacity above the transition point is calculated first for the Gaussian
      model and then taking the cubic and the quartic terms as a perturbation. The
      theoretical results are found to be in good agreement with experiment.

PMID- 16089750
TI  - Electric-field-induced deformation dynamics of a single nematic disclination.
AB  - Disclinations in nematic liquid crystals usually adopt a straight shape in order
      to minimize their elastic energy. Once created in the course of a nonequilibrium
      process such as a temperature quench from the isotropic to the nematic phase, the
      topologically stable disclinations of half-integer strength either annihilate
      each other in pairs of opposite strength or form topologically unstable
      disclinations of integer strength. In this article, we demonstrate that the
      annihilation process can be inhibited and the defects can be deformed by an
      applied electric field. We study the disclination lines in the deep uniaxial
      nematic phase, located at the boundary between two different types of walls, the
      so-called pi wall (a planar soliton stabilized by the surface anchoring) and the
      Brochard-Leger (BL) wall stabilized by the applied electric field. By changing
      the electric voltage, one can control the energy of director deformations
      associated with the two walls and thus control the deformation and dynamics of
      the disclination line. At small voltages, the disclinations are straight lines
      connecting the opposite plates of the cell, located at the two ends of the pi
      walls. The pi walls tend to shrink. When the voltage increases above E(F), the
      Freedericksz threshold, the BL walls appear and connect pairs of disclinations
      along a path complementary to the pi wall. At E>2 E(F), the BL walls store
      sufficient energy to prevent shrinking of the pi walls. Reconstruction of the
      three-dimensional director configuration using a fluorescent confocal polarizing
      microscopy demonstrates that the disclinations are strongly bent in the region
      between the pi and the BL walls. The distortions and the related dynamics are
      associated with the transformation of the BL wall into two surface disclination
      lines; we characterize it experimentally as a function of the applied electric
      field, the cell thickness, and the sample temperature. A simple model captures
      the essential details of the experimental data.

PMID- 16089751
TI  - Waves at the nematic-isotropic interface: thermotropic nematogen-non-nematogen
      mixtures.
AB  - We develop a theory for surface modes at the nematic-isotropic interface in
      thermotropic nematogen-non-nematogen mixtures. We employ the dynamical
      generalization of the Landau-de Gennes model for the orientational (nonconserved)
      order parameter, coupled with the Cahn-Hilliard equation for concentration
      (conserved parameter), and include hydrodynamic degrees of freedom. The theory
      uses a generalized form of the Landau-de Gennes free-energy density to include
      the coupling between the concentration of the non-nematogen fluid and the
      orientational order parameter. Two representative phase diagrams are shown. The
      method of matched asymptotic expansions is used to obtain a generalized
      dispersion relation. Further analysis is made in particular cases. Orientational
      order parameter relaxation dominates in the short-wavelength limit, while in the
      long-wavelength limit viscous damping processes become important. There is an
      intermediate region (depending on the temperature) in which the interaction
      between conserved parameter dynamics and hydrodynamics is important.

PMID- 16089752
TI  - Determination of liquid-crystal polar anchoring energy by electrical
      measurements.
AB  - We propose a simple method for the determination of liquid-crystal (LC) polar
      anchoring energy by electrical measurements. The basic idea of this method is a
      two-channel scheme for capacitance measurements. The first channel uses one cell
      with a planar LC cell, while the second a LC cell with vertical alignment. One of
      the LC cells can have a high pretilt angle. The proposed method allows
      investigating anchoring properties of both planar and vertical aligned LC
      materials. Simultaneous measurements of the two cells compensate all volume
      effects in LC bulk and provide a good opportunity to study directly the LC
      surface interaction. The method can be applied for LC cells, which do not have
      uniform azimuthal orientation. We used this method to investigate the polar
      anchoring properties of photoaligning material before and after illumination and
      for LC structures with a high pretilt angle.

PMID- 16089753
TI  - Defect modes in a stacked structure of chiral photonic crystals.
AB  - An optical propagation simulation is carried out for the study of photonic defect
      modes in a stacked structure of cholesteric liquid crystal films with spatially
      varying pitch. The defects are introduced by a pitch jump and a phase jump in the
      cholesteric helix. The effect of a finite sample thickness on transmission of the
      defect mode and on the required polarization of incident light to create the
      defect mode is discussed. For normal and near-normal incidence of circularly
      polarized light with the same handedness as structure, the defect caused by a
      pitch jump results in discrete peaks within a forbidden band in the transmission.
      The particular spectrum is similar to the feature of a Fabry-Perot
      interferometer. By introducing an additional phase jump, linear blueshifts of the
      defect modes in transmission spectra are correlated with an increase in the twist
      angle.

PMID- 16089754
TI  - Annihilation dynamics of umbilical defects in nematic liquid crystals under
      applied electric fields.
AB  - Umbilical defects were induced in a nematic liquid crystal with negative
      dielectric anisotropy, confined to Hele-Shaw cells with homeotropic boundary
      conditions, and their annihilation dynamics were investigated experimentally.
      Dynamic scaling laws, previously proposed for Schlieren defects, were verified
      also for electric field induced umbilical defects while varying external
      parameters, such as electric field amplitude, frequency, Hele-Shaw cell gap, and
      temperature. In all cases, scaling relations of rho(t) proportional to t(-1) for
      the defect density and D proportional to (t(0) - t)(1/2) for the defect pair
      separation were obtained, independent of external field parameters. The
      experimental results give evidence of the universality of scaling relations for
      the annihilation of topological defects in liquid crystals, extended to umbilical
      defects and their annihilation dynamics under applied external fields.

PMID- 16089755
TI  - Pattern formation in thin polystyrene films induced by an enhanced mobility in
      ambient air.
AB  - Thin polystyrene films (prepared in a sandwich geometry between two aluminum
      electrodes) develop a characteristic pattern in ambient air when kept above the
      glass-transition temperature, whereas they remain unchanged in vacuum or in a
      pure nitrogen atmosphere. Measurements by broadband dielectric spectroscopy,
      capacitive dilatometry, and AC calorimetry reveal that the pattern formation is
      initiated in ambient air by an increase in the average relaxation rate of the
      dynamic glass transition, which results in a corresponding reduction of the glass
      transition temperature. Infrared measurements evidence that this is caused by a
      shift of the molecular weight distribution to lower values as a consequence of
      oxygen-induced chain scissions.

PMID- 16089756
TI  - Directed polymers with constrained winding angle.
AB  - In this paper we study from a nonperturbative point of view the entanglement of
      two directed polymers subjected to repulsive interactions given by a Dirac delta
      function potential. An exact formula of the so-called second moment of the
      winding angle is derived. This result is used to provide a thorough analysis of
      entanglement phenomena in the classical system of two polymers subjected to
      repulsive interactions and related problems. No approximation is made in treating
      the constraint on the winding angle and the repulsive forces. In particular, we
      investigate how repulsive forces influence the entanglement degree of the two
      polymer system. In the limit of ideal polymers, in which the interactions are
      switched off, we show that our results are in agreement with those of previous
      works.

PMID- 16089757
TI  - Ordering mechanisms in two-dimensional sphere-forming block copolymers.
AB  - We study the coarsening dynamics of two-dimensional hexagonal patterns formed by
      single microdomain layers of block copolymers, using numerical simulations. Our
      study is focused on the temporal evolution of the orientational correlation
      length, the interactions between topological defects, and the mechanisms of
      coarsening. We find no free disclinations in the system; rather, they are located
      on large-angle grain boundaries, commonly where such boundaries bifurcate. The
      correlation lengths determined from the scattering function, from the density of
      dislocations, and from the density of disclinations exhibit similar behavior and
      grow with time according to a power law. The orientational correlation length
      also grows following a power law, but with a higher exponent than the other
      correlation lengths. The orientational correlation length grows via annihilation
      of dislocations, through preferential annihilation of small-angle grain
      boundaries due to poor screening of the strain field around dislocations located
      on small-angle grain boundaries. Consequently, the patterns are characterized by
      large-angle grain boundaries. The most commonly observed mechanism of coarsening
      is the collapse of smaller grains residing on the boundary of two larger grains
      delimited by large-angle grain boundaries. Simulations agree remarkably well with
      experimental results recently obtained.

PMID- 16089758
TI  - Kinetics of the polymer collapse transition: the role of hydrodynamics.
AB  - We investigate numerically the dynamical behavior of a polymer chain collapsing
      in a dilute solution. The rate of collapse is measured with and without the
      presence of hydrodynamic interactions. We find that hydrodynamic interactions
      accelerate polymer collapse. We present a scaling theory describing the physical
      process responsible for the collapse kinetics. Predicted collapse times in a
      hydrodynamic (tauH approximately N(4/3)) and a Brownian heat bath (tauB
      approximately N2) agree well with the numerical results (tauH approximately
      N(1.40+/-0.08) and tauB approximately N(1.89+/-0.09)) where N denotes chain
      length. The folding kinetics of Go models of proteins is also examined. We show
      that for these systems, where many free energy minima compete, hydrodynamics has
      little effect on the kinetics.

PMID- 16089759
TI  - Breather-induced anomalous charge diffusion.
AB  - We present results on the diffusive motion of a charge interacting with the
      nonlinear dynamics of a thermalized underlying lattice. Signatures of anomalous
      diffusive properties are found at relatively high temperatures, where highly
      nonlinear excitations are present. A sublinear diffusion and a plateau appear
      before the standard long-time diffusion during the evolution of the mean-squared
      displacement and a significant degree of heterogeneity is exhibited among
      individual trajectories. Both properties are connected with the existence of
      vibrational hot spots (breather or multibreather excitations). Transport
      parameters of the charge are strongly affected in this case, as can be
      exemplified by the significant suppression of the diffusion coefficient D. The
      variation of D with temperature follows a stretched exponential law. The results
      are contrasted with those of the linearized case, in the absence of breathers.
      Such anomalous diffusion of a charge coupled to a thermalized lattice may be
      relevant in low-dimensional soft materials with strong anharmonicities, such as
      biomolecules, conducting polymers, etc.

PMID- 16089760
TI  - Effective adhesion strength of specifically bound vesicles.
AB  - A theoretical approach has been undertaken in order to model the thermodynamic
      equilibrium of a 3D vesicle adhering to a flat substrate. The vesicle is treated
      in a canonical description with a fixed number of sites. A finite number of these
      sites are occupied by mobile ligands that are capable of interacting with a
      discrete number of receptors immobilized on the substrate. Explicit consideration
      of the bending energy of the vesicle shape has shown that the problem of the
      vesicle shape can be decoupled from the determination of the optimum allocation
      of ligands over the vesicle. The allocation of bound and free ligands in the
      vesicle can be determined as a function of the size of the contact zone, the
      ligand-receptor binding strength, and the concentration of the system
      constituents. Several approximate solutions for different regions of system
      parameters are determined and in particular, the distinction between receptor-
      and ligand-dominated equilibria is found to be important. The crossover between
      these two types of solutions is found to occur at a critical size of the contact
      zone. The presented approach enables the calculation of the effective adhesion
      strength of the vesicle and thus permits meaningful comparisons with relevant
      experiments as well as connecting the presented model with the proven success of
      the continuum approach for modeling the shapes of adhering vesicles. The behavior
      of the effective adhesion strength is analyzed in detail and several approximate
      expressions for it are given.

PMID- 16089761
TI  - Physical mechanisms of rehydration in Polypodium polypodioides, a resurrection
      plant.
AB  - Resurrection plants have an amazing ability to withstand water drought. Here we
      investigate experimentally the rapidity of such revivals using the resurrection
      fern (Polypodium polypodioides) as a model example. Upon drying, the leaves of
      the resurrection fern fold into a thin cylindrical shell, thus protecting the
      photosynthetic area from light. In the dry state the fern looks dead, but will
      quickly come back once exposed to water by unfolding the cylindrical shell into a
      nearly planar sheet. We investigate here the mass and radius of curvature of the
      cylindrical shell as a function of time after rehydration and develop a
      phenomenological model to describe the observed phenomena. In particular, we
      demonstrate that the mass of the rehydrating plant follows a simple kinetic
      relationship, whereas the unfolding is governed by a more complex nonlinear
      constitutive relationship between the water uptake and the induced strain.

PMID- 16089762
TI  - Stability of synchronous oscillations in a system of Hodgkin-Huxley neurons with
      delayed diffusive and pulsed coupling.
AB  - We study the synchronization dynamics for a system of two Hodgkin-Huxley (HH)
      neurons coupled diffusively or through pulselike interactions. By calculating the
      maximum transverse Lyapunov exponent, we found that, with diffusive coupling,
      there are three regions in the parameter space, corresponding to qualitatively
      distinct behaviors of the coupled dynamics. In particular, the two neurons can
      synchronize in two regions and desynchronize in the third. When excitatory and
      inhibitory pulse coupling is considered, we found that synchronized dynamics
      becomes more difficult to achieve in the sense that the parameter regions where
      the synchronous state is stable are smaller. Numerical simulations of the coupled
      system are presented to validate these results. The stability of a network of
      coupled HH neurons is then analyzed and the stability regions in the parameter
      space are exactly obtained.

PMID- 16089763
TI  - Statistics of loop formation along double helix DNAs.
AB  - We compute relative position distributions of distant sites along discretized
      semiflexible polymers, focusing on encounter statistics for pairs of sites along
      a double-stranded DNA molecule (dsDNA), using a transfer-matrix approach. We
      generalize the usual semiflexible polymer, considering nonlinear elasticity
      effects arising from inhomogeneities which either appear at any position via
      thermal fluctuation, or which occur at specific "quenched" locations. We apply
      our theory to two problems associated with dsDNA looping. First, we discuss how
      local flexible defects in double-helix structure facilitate cyclization of short
      dsDNA molecules. Flexible defects greatly enhance cyclization rate, and strongly
      modify its dependence on the closure orientational boundary condition. This
      effect is relevant to free-solution cyclization experiments, and to loop
      formation in vivo. Second, we present calculations of force dependence of the
      probability of formation of loops along single dsDNAs which show how the
      probability of loop formation is suppressed by tension.

PMID- 16089764
TI  - Non-Markovian stochastic resonance: three-state model of ion channel gating.
AB  - Stochastic resonance in single voltage-dependent ion channels is investigated
      within a three-state non-Markovian modeling of the ion channel conformational
      dynamics. In contrast to a two-state description one assumes the presence of an
      additional closed state for the ion channel which mimics the manifold of voltage
      independent closed subconformations (inactivated "state"). The conformational
      transition into the open state occurs through a domain of voltage-dependent
      closed subconformations (closed "state"). At distinct variance with the standard
      two-state and also the three-state Markovian approach, the inactivated state is
      characterized by a broad, nonexponential probability distribution of
      corresponding residence times. The linear response to a periodic voltage signal
      is determined for arbitrary distributions of the channel's recovery times.
      Analytical results are obtained for the spectral amplification of the applied
      signal and the corresponding signal-to-noise ratio. Alternatively, these results
      are also derived by use of a corresponding two-state non-Markovian theory which
      is based on driven integral renewal equations [I. Goychuk and P. Hanggi, Phys.
      Rev. E 69, 021104 (2004)]. The non-Markovian features of stochastic resonance are
      studied for a power law distribution of the residence time intervals in the
      inactivated state which exhibits a large variance. A comparison with the case of
      biexponentially distributed residence times possessing the same mean value, i.e.,
      the simplest non-Markovian two-state description, is also presented.

PMID- 16089765
TI  - Convergence of stochastic learning in perceptrons with binary synapses.
AB  - The efficacy of a biological synapse is naturally bounded, and at some
      resolution, and is discrete at the latest level of single vesicles. The finite
      number of synaptic states dramatically reduce the storage capacity of a network
      when online learning is considered (i.e., the synapses are immediately modified
      by each pattern): the trace of old memories decays exponentially with the number
      of new memories (palimpsest property). Moreover, finding the discrete synaptic
      strengths which enable the classification of linearly separable patterns is a
      combinatorially hard problem known to be NP complete. In this paper we show that
      learning with discrete (binary) synapses is nevertheless possible with high
      probability if a randomly selected fraction of synapses is modified following
      each stimulus presentation (slow stochastic learning). As an additional
      constraint, the synapses are only changed if the output neuron does not give the
      desired response, as in the case of classical perceptron learning. We prove that
      for linearly separable classes of patterns the stochastic learning algorithm
      converges with arbitrary high probability in a finite number of presentations,
      provided that the number of neurons encoding the patterns is large enough. The
      stochastic learning algorithm is successfully applied to a standard
      classification problem of nonlinearly separable patterns by using multiple,
      stochastically independent output units, with an achieved performance which is
      comparable to the maximal ones reached for the task.

PMID- 16089766
TI  - Molecular motions in lipid bilayers studied by the neutron backscattering
      technique.
AB  - We report a high energy-resolution neutron backscattering study to investigate
      slow motions on nanosecond time scales in highly oriented solid supported
      phospholipid bilayers of the model system DMPC-d54 (deuterated 1,2-dimyristoyl-sn
      glycero-3-phoshatidylcholine), hydrated with heavy water. This technique allows
      to discriminate the onset of mobility at different length scales for the
      different molecular components, as, e.g., the lipid acyl-chains and the hydration
      water in between the membrane stacks, respectively, and provides a benchmark test
      regarding the feasibility of neutron backscattering investigations on these
      sample systems. We discuss freezing of the lipid acyl-chains, as observed by this
      technique, and observe a second freezing transition which we attribute to the
      hydration water.

PMID- 16089767
TI  - Synchronization and coordination of sequences in two neural ensembles.
AB  - There are many types of neural networks involved in the sequential motor behavior
      of animals. For high species, the control and coordination of the network
      dynamics is a function of the higher levels of the central nervous system, in
      particular the cerebellum. However, in many cases, especially for invertebrates,
      such coordination is the result of direct synaptic connections between small
      circuits. We show here that even the chaotic sequential activity of small model
      networks can be coordinated by electrotonic synapses connecting one or several
      pairs of neurons that belong to two different networks. As an example, we
      analyzed the coordination and synchronization of the sequential activity of two
      statocyst model networks of the marine mollusk Clione. The statocysts are gravity
      sensory organs that play a key role in postural control of the animal and the
      generation of a complex hunting motor program. Each statocyst network was modeled
      by a small ensemble of neurons with Lotka-Volterra type dynamics and nonsymmetric
      inhibitory interactions. We studied how two such networks were synchronized by
      electrical coupling in the presence of an external signal which lead to
      winnerless competition among the neurons. We found that as a function of the
      number and the strength of connections between the two networks, it is possible
      to coordinate and synchronize the sequences that each network generates with its
      own chaotic dynamics. In spite of the chaoticity, the coordination of the signals
      is established through an activation sequence lock for those neurons that are
      active at a particular instant of time.

PMID- 16089768
TI  - Lattice model for calcium dynamics.
AB  - We present a simplified lattice model to study calcium dynamics in the
      endoplasmic reticulum membrane. Calcium channels and calcium ions are placed in
      two interpenetrating square lattices which are connected in two ways: (i) via
      calcium release and (ii) because transitions between channel states are calcium
      dependent. The opening or closing of a channel is a stochastic process controlled
      by two functions which depend on the calcium density on the channel neighborhood.
      The model is studied through mean field calculations and simulations. We show
      that the critical behavior of the model changes drastically depending on the
      opening/closing functions. For certain choices of these functions, all channels
      are closed at very low and high calcium densities and the model presents one
      absorbing state.

PMID- 16089769
TI  - Duplication-divergence model of protein interaction network.
AB  - We investigate a very simple model describing the evolution of protein-protein
      interaction networks via duplication and divergence. The model exhibits a
      remarkably rich behavior depending on a single parameter, the probability to
      retain a duplicated link during divergence. When this parameter is large, the
      network growth is not self-averaging and an average node degree increases
      algebraically. The lack of self-averaging results in a great diversity of
      networks grown out of the same initial condition. When less than a half of links
      are (on average) preserved after divergence, the growth is self-averaging, the
      average degree increases very slowly or tends to a constant, and a degree
      distribution has a power-law tail. The predicted degree distributions are in a
      very good agreement with the distributions observed in real protein networks.

PMID- 16089770
TI  - Interpreting two-photon imaging data of lymphocyte motility.
AB  - Recently, using two-photon imaging it has been found that the movement of B and T
      cells in lymph nodes can be described by a random walk with persistence of
      orientation in the range of 2 minutes. We interpret this new class of lymphocyte
      motility data within a theoretical model. The model considers cell movement to be
      composed of the movement of subunits of the cell membrane. In this way movement
      and deformation of the cell are correlated to each other. We find that, indeed,
      the lymphocyte movement in lymph nodes can best be described as a random walk
      with persistence of orientation. The assumption of motility induced cell
      elongation is consistent with the data. Within the framework of our model the two
      photon data suggest that T and B cells are in a single velocity state with large
      stochastic width. The alternative of three different velocity states with
      frequent changes of their state and small stochastic width is less likely. Two
      velocity states can be excluded.

PMID- 16089771
TI  - Temperature dependence and counter effect of the correlations of folding rate
      with chain length and with native topology.
AB  - There is a controversy about the major determinants of the folding rate of small
      single-domain proteins. To shed light on this issue, we examined a possibility
      that the major determinants may change depending on temperature by conducting
      molecular dynamics simulations for 17 small single-domain proteins using an off
      lattice Go-like model over a wide range of temperature. It was shown that the
      rank order of the folding rates is temperature dependent, which indicates that
      the major determinants are dependent on temperature. It was also found that as
      temperature is decreased, the correlation of the folding rate with the chain
      length becomes weakened, whereas that with the native topology becomes enhanced.
      Our simulation results, therefore, may provide a clue to reconcile the apparent
      controversy between the study by Plaxco based on experimental data and the
      previous theoretical and subsequent simulation studies: the former showed that
      the folding rate of two-state folders does not correlate with the chain length
      but correlates well with the native topology, whereas the latter showed that the
      folding rate does correlate with the chain length. We propose a possible scenario
      reconciling the controversy, explaining the reason why the correlation of the
      folding rate with the chain length became weakened and that with the native
      topology became enhanced with decreasing temperature.

PMID- 16089772
TI  - Cluster synchronization in an ensemble of neurons interacting through chemical
      synapses.
AB  - In networks of periodically firing spiking neurons that are interconnected with
      chemical synapses, we analyze a cluster state, where an ensemble of neurons are
      subdivided into a few clusters, in each of which neurons exhibit perfect
      synchronization. To clarify stability of the cluster state, we decompose linear
      stability of the solution into two types of stabilities, stability of a mean
      state and stabilities of clusters. Computing Floquet matrices for these
      stabilities, we clarify the total stability of the cluster state for any type of
      neuron and any strength of interaction even if the size of networks is infinitely
      large. First, we apply this stability analysis to investigating synchronization
      in the large ensemble of integrate-and-fire (IF) neurons. In one-cluster state we
      find the change of stability of a cluster, which elucidates that in-phase
      synchronization of IF neurons occurs with only inhibitory synapses. Then, we
      investigate entrainment of two clusters of IF neurons with different
      excitability. IF neurons with fast decaying synapses show low entrainment
      capability, which is explained by a pitchfork bifurcation appearing in the two
      cluster state with change of synapse decay time constant. Second, we analyze a
      one-cluster state of Hodgkin-Huxley (HH) neurons and discuss the difference in
      synchronization properties between IF neurons and HH neurons.

PMID- 16089773
TI  - Models of stochastic biperiodic oscillations and extended serial correlations in
      electroreceptors of paddlefish.
AB  - Two types of minimal models were used to study stochastic oscillations in sensory
      receptors composed of two coupled oscillators, as in the electroreceptors of
      paddlefish. They have populations of cells in sensory epithelia undergoing
      approximately 26 Hz oscillations. These are coupled unidirectionally via synaptic
      excitation to a few afferent neurons, each of whose terminal contains a 30-70 Hz
      oscillator, expressed as a dominant peak in the power spectra of spontaneous
      afferent firing, corresponding to the mean firing rate. The two distinct types of
      internal noisy oscillators result in stochastic biperiodic firing patterns of the
      primary afferent sensory neurons. However, the functions of the oscillations have
      remained elusive, motivating this study. The models we used here are based on the
      circle map, or on the Ermentraut-Koppell canonical phase (theta neuron) model.
      Parameters were chosen according to experimental data. We used the models to
      demonstrate that the presence of epithelial oscillations leads to extended
      negative correlations of afferent interspike intervals, and to show that the
      correlation structure depends crucially on the ratio of the afferent to
      epithelial oscillation frequencies, being most pronounced when this ratio is
      close to 2, as observed in experiments. Our studies of stochastic versions of
      these models are of general interest for a wide range of coupled excitable
      systems, especially for understanding the functional roles of noisy oscillations
      in auditory and other types of "hair cell-primary afferent" sensory receptors.

PMID- 16089774
TI  - Internal noise stochastic resonance for intracellular calcium oscillations in a
      cell system.
AB  - By constructing a mesoscopic stochastic model for intracellular calcium
      oscillations in a cell system, we have investigated how the internal noise would
      influence the calcium oscillations of such a system using stochastic simulation
      methods and chemical Langevin method. It is found that stochastic calcium
      oscillations appear when the internal noise is considered, while the
      deterministic model only yields steady state. The performance of such
      oscillations undergoes a maximum with the variation of the internal noise level,
      indicating the occurrence of internal noise stochastic resonance. Interestingly,
      we find that the optimal system size matches well with the real cell size when
      the control parameter is tuned near the left Hopf bifurcation point, and such a
      match is robust to the variation of the control parameters.

PMID- 16089775
TI  - Event and time-scale characteristics of heart-rate dynamics.
AB  - The cardiac system shows various scale dynamic activities from secondly to
      yearly. Therefore multiple time-scale characteristics of heart dynamics have
      received much attention for understanding and distinguishing healthy and
      pathological cardiac systems. In this paper we expand the multiple time-scale
      analysis into event and time scales to investigate scale characteristics in
      healthy and pathologic cardiac systems. To do this, we define a measure based on
      symbolic dynamics, which calculates complexity at each time and event scale,
      called the unit time block entropy (UTBE). This measure allows a reliable
      comparison of experimental data through matching the number of words and the
      total measurement time at the same time for all RR interval sequences which are
      composed of the time durations between consecutive R waves of electrocardiograms.
      We apply the UTBE to the healthy heart-rate (HR) group and pathological HR groups
      and find that the RR interval acceleration is more effective than the RR interval
      in distinguishing each group. And we also find that the normal and pathological
      HR groups are clearly distinguished in some specific event and time-scale
      regions.

PMID- 16089776
TI  - Analytical derivation of thermodynamic characteristics of lipid bilayer from a
      flexible string model.
AB  - We introduce a flexible string model of the hydrocarbon chain and derive an
      analytical expression for the lateral pressure profile across the hydrophobic
      core of the membrane. The pressure profile influences the functioning of the
      embedded proteins and is difficult to measure experimentally. In our model the
      hydrocarbon chain is represented as a flexible string of finite thickness with a
      given bending rigidity. In the mean-field approximation we substitute the
      entropic repulsion between neighboring chains in a lipid membrane by an effective
      potential. The effective potential is determined self-consistently. The arbitrary
      chain conformation is expanded over eigenfunctions of the self-adjoint operator
      of the chain energy density. The lateral pressure distribution across the bilayer
      is calculated using the path integral technique. We found that the pressure
      profile is mainly formed by the sum of the partial contributions of a few
      discrete lowest-energy "eigenconformations." The dependences on temperature and
      area per lipid of the lateral pressure produced by the hydrocarbon chains are
      found. We also calculated the chain contribution to the area compressibility
      modulus and the temperature coefficient of area expansion.

PMID- 16089777
TI  - Pulse requirements for x-ray diffraction imaging of single biological molecules.
AB  - In this paper we estimate the required pulse parameters for the future
      application of x-ray free electron lasers to imaging single biological molecules.
      The parameters are determined by a tradeoff between minimizing image degradation
      due to damage and maximizing the image signal-to-noise ratio. We discuss several
      means to alleviate the pulse requirements, and compare the requirements with
      parameters of two planned x-ray lasers.

PMID- 16089778
TI  - Relaxation dynamics of a single DNA molecule.
AB  - The relaxation of a single DNA molecule is studied. The experimental system
      consists of optical tweezers and a micron-sized bead that is tethered to the
      bottom of the sample by a single double-stranded DNA molecule. The bead slows
      down the DNA relaxation from a strongly stretched configuration such that it is
      passing through stretched equilibrium states. This allows for a theoretical
      description of the relaxation trajectory, which is in good agreement with
      experiment.

PMID- 16089779
TI  - Adaptive walk on complex networks.
AB  - We investigate the properties of adaptive walks on an uncorrelated fitness
      landscape which is established in sequence spaces of complex structure. In
      particular, we perform numerical simulations of adaptive walks on random graphs
      and scale-free networks. For the former, we also derive some analytical
      approximations for the density of local optima of the fitness landscape and the
      mean length walk. We compare our results with those obtained for regular
      lattices. We obtain that the density of local optima decreases as 1/z, where z is
      the mean connectivity, for all networks we have investigated. In random graphs,
      the mean length walk L reaches the asymptotic value e - 1 for large z, which
      corresponds to the result for regular networks. Although we could not find an
      exact estimate, we derive an underestimated value for L. Unlike random graphs,
      scale-free networks show an upper asymptotic value of L.

PMID- 16089780
TI  - Partly melted DNA conformations obtained with a probability peak finding method.
AB  - Peaks in the probabilities of loops or bubbles, helical segments, and unzipping
      ends in melting DNA are found in this article using a peak finding method that
      maps the hierarchical structure of certain energy landscapes. The peaks indicate
      the alternative conformations that coexist in equilibrium and the range of their
      fluctuations. This yields a representation of the conformational ensemble at a
      given temperature, which is illustrated in a single diagram called a stitch
      profile. This article describes the methodology and discusses stitch profiles vs
      the ordinary probability profiles using the phage lambda genome as an example.

PMID- 16089781
TI  - Dynamic hysteresis in a one-dimensional Ising model: application to allosteric
      proteins.
AB  - We solve exactly the problem of dynamic hysteresis for a finite one-dimensional
      Ising model at low temperature. We find that the area of the hysteresis loop, as
      the field is varied periodically, scales as the square root of the field
      frequency for a large range of frequencies. Below a critical frequency there is a
      correction to the scaling law, resulting in a linear relationship between
      hysteresis area and frequency. The one-dimensional Ising model provides a
      simplified description of switchlike behavior in allosteric proteins, such as
      hemoglobin. Thus our analysis predicts the switching dynamics of allosteric
      proteins when they are exposed to a ligand concentration which changes with time.
      Many allosteric proteins bind a regulator that is maintained at a nonequilibrium
      concentration by active signal transduction processes. In the light of our
      analysis, we discuss to what extent allosteric proteins can respond to changes in
      regulator concentration caused by an upstream signaling event, while remaining
      insensitive to the intrinsic nonequilibrium fluctuations in regulator level which
      occur in the absence of a signal.

PMID- 16089782
TI  - Structure of phospholipid-cholesterol membranes: an x-ray diffraction study.
AB  - We have studied the phase behavior of mixtures of cholesterol with dipalmitoyl
      phosphatidylcholine (DPPC), dimyristoyl phosphatidylcholine (DMPC), and dilauroyl
      phosphatidylethanolamine (DLPE), using x-ray diffraction techniques.
      Phosphatidylcholine (PC)-cholesterol mixtures are found to exhibit a modulated
      phase for cholesterol concentrations around 15 mol % at temperatures below the
      chain melting transition. Lowering the relative humidity from 98% to 75%
      increases the temperature range over which it exists. An electron density map of
      this phase in DPPC-cholesterol mixtures, calculated from the x-ray diffraction
      data, shows bilayers with a periodic height modulation, as in the ripple phase
      observed in many PCs in between the main- and pretransitions. However, these two
      phases differ in many aspects, such as the dependence of the modulation
      wavelength on the cholesterol content and thermodynamic stability at reduced
      humidities. This modulated phase is found to be absent in DLPE-cholesterol
      mixtures. At higher cholesterol contents the gel phase does not occur in any of
      these three systems, and the fluid lamellar phase is observed down to the lowest
      temperature studied (5 degrees C).

PMID- 16089784
TI  - Estimating phase synchronization in dynamical systems using cellular nonlinear
      networks.
AB  - We propose a method for estimating phase synchronization between time series
      using the parallel computing architecture of cellular nonlinear networks (CNN's).
      Applying this method to time series of coupled nonlinear model systems and to
      electroencephalographic time series from epilepsy patients, we show that an
      accurate approximation of the mean phase coherence R--a bivariate measure for
      phase synchronization--can be achieved with CNN's using polynomial-type
      templates.

PMID- 16089783
TI  - Compositional searching of CpG islands in the human genome.
AB  - We report on an entropic edge detector based on the local calculation of the
      Jensen-Shannon divergence with application to the search for CpG islands. CpG
      islands are pieces of the genome related to gene expression and cell
      differentiation, and thus to cancer formation. Searching for these CpG islands is
      a major task in genetics and bioinformatics. Some algorithms have been proposed
      in the literature, based on moving statistics in a sliding window, but its size
      may greatly influence the results. The local use of Jensen-Shannon divergence is
      a completely different strategy: the nucleotide composition inside the islands is
      different from that in their environment, so a statistical distance--the Jensen
      Shannon divergence--between the composition of two adjacent windows may be used
      as a measure of their dissimilarity. Sliding this double window over the entire
      sequence allows us to segment it compositionally. The fusion of those segments
      into greater ones that satisfy certain identification criteria must be achieved
      in order to obtain the definitive results. We find that the local use of Jensen
      Shannon divergence is very suitable in processing DNA sequences for searching for
      compositionally different structures such as CpG islands, as compared to other
      algorithms in literature.

PMID- 16089785
TI  - Control of relative radiation pressure in optical traps: application to
      phagocytic membrane binding studies.
AB  - We show how to control the relative radiation pressure and thereby the stable
      trap position of an optically trapped bead by variation of the mean incident
      axial photon momentum. The thermal position fluctuations of a trapped bead are
      recorded by a three-dimensional back-focal-plane interferometry. The
      interferometric detection signals are in agreement with predictions based on an
      extended Mie theory. Depending on the application, the unique and linear range of
      such a detection system can be optimized by controlling the trap position of the
      bead. We use this method to investigate in three dimensions the binding of beads
      to membranes of living cells during phagocytosis. We found that independent of
      the bead coating (IgG, complement, LPS, avidin) the most frequent initial
      mechanical response of the cell was a downward pulling of the bead into the cell.
      The time delay between binding and response was on average 2 s.

PMID- 16089786
TI  - Electrostatics and the assembly of an RNA virus.
AB  - Electrostatic interactions play a central role in the assembly of single-stranded
      RNA viruses. Under physiological conditions of salinity and acidity, virus capsid
      assembly requires the presence of genomic material that is oppositely charged to
      the core proteins. In this paper we apply basic polymer physics and statistical
      mechanics methods to the self-assembly of a synthetic virus encapsidating generic
      polyelectrolyte molecules. We find that (i) the mean concentration of the
      encapsidated polyelectrolyte material depends on the surface charge density, the
      radius of the capsid, and the linear charge density of the polymer but neither on
      the salt concentration nor the Kuhn length, and (ii) the total charge of the
      capsid interior is equal but opposite to that of the empty capsid, a form of
      charge reversal. Unlike natural viruses, synthetic viruses are predicted not to
      be under an osmotic swelling pressure. The design condition that self-assembly
      only produces filled capsids is shown to coincide with the condition that the
      capsid surface charge exceeds the desorption threshold of polymer surface
      adsorption. We compare our results with studies on the self-assembly of both
      synthetic and natural viruses.

PMID- 16089787
TI  - Coherence resonance in excitable electronic circuits in the presence of colored
      noise.
AB  - We give evidence of coherence resonance in an excitable electronic circuit whose
      dynamics obeys the FitzHugh-Nagumo model system, under the application of
      different noise sources, ranging from Gaussian white noise to colored 1/f2
      noises. The resonance behavior can be significantly reinforced when experimental
      parameters are tuned in order to place the stable fixed point closer to the
      excitability threshold of spiking behavior, as well as when the time scales of
      the circuit are properly modified. A quantitative description of the effects of
      noise correlations in inducing the resonant behavior is provided.

PMID- 16089788
TI  - Nonlinear response of permanent dipoles in a uniaxial potential to alternating
      fields.
AB  - It is shown how the existing theory of the dynamic Kerr effect and nonlinear
      dielectric relaxation based on the noninertial Brownian rotation of
      noninteracting rigid dipolar particles may be generalized to take into account
      interparticle interactions using the Maier-Saupe mean field potential. The
      results (available in simple closed form) suggest that the frequency dependent
      nonlinear response provides a method of measuring the Kramers escape rate (or in
      the analogous problem of magnetic relaxation of fine single domain ferromagnetic
      particles, the superparamagnetic relaxation time).

PMID- 16089789
TI  - Addendum to "Colored-noise-induced discontinuous transitions in symbiotic
      ecosystems".
AB  - A symbiotic ecosystem with Gompertz self-regulation and with adaptive competition
      between populations is studied by means of a N-species Lotka-Volterra stochastic
      model. The influence of fluctuating environment on the carrying capacity of a
      population is modeled as a dichotomous noise. The study is a follow up of
      previous investigations of symbiotic ecosystems subjected to the generalized
      Verhulst self-regulation [Phys. Rev. E 69, 061106 (2004); 65, 051108 (2002)]. In
      the framework of mean-field approximation the behavior of the solutions of the
      self-consistency equation for a stationary system is examined analytically in the
      full phase space of system parameters. Depending on the mutual interplay of
      symbiosis and competition of species, variation of noise parameters (amplitude,
      correlation time) can induce doubly unidirectional discontinuous transitions as
      well as single unidirectional discontinuous transitions of the mean population
      size.

PMID- 16089790
TI  - Influence of adsorption phenomenon on the impedance spectroscopy of a cell of
      liquid.
AB  - We investigate the influence of the adsorption phenomenon on the impedance
      spectroscopy measurements. The analysis is performed by assuming that the ions
      have the same mobility and the electrodes are perfectly blocking. We find that in
      the low frequency range the presence of the adsorption phenomenon is responsible
      for an increasing of the real part of the impedance of the cell, similar to the
      one usually described by means of the impedance of the metal-electrolyte
      interface. The frequency dependencies theoretically predicted by our model for
      the real and imaginary parts of the complex dielectric constant are in
      qualitative agreement with the experimental data published by other groups.

PMID- 16089791
TI  - Anisotropic dynamics in a shaken granular dimer gas experiment.
AB  - The dynamics, velocity fluctuations, and particle-plate interactions for a two
      dimensional granular gas of shaken, nonspherical particles are studied
      experimentally. The experiment consists of a horizontal plate that is vertically
      oscillated to drive the dynamics of macroscopic dimers, spherical pairs that are
      loosely connected by a rod that couple the interaction each of the spheres has
      with the shaking plate. The extended nature of the particles results in more than
      one energy-momentum transfer between the plate and each dimer per shaking cycle.
      This complex interaction results in anisotropic behavior for the dimer that is a
      function of the shaking parameters.

PMID- 16089792
TI  - Multistep radial melting in small two-dimensional classical clusters.
AB  - We report on a molecular dynamics study of small classical two-dimensional
      clusters with ringlike configurations. We focus on the particles motion at low
      temperatures before the radial and angular melting sets in. It is shown that in
      magic number configurations a local radial melting of subshells occur, which is
      related to the intershell rotation.

PMID- 16089793
TI  - Monolayer to bilayer transition in a dipolar system.
AB  - We study the transition from a one-dimensional magnetic dipolar monolayer to a
      bilayer as it is compressed beyond the close-packed condition. The pressure in a
      close-packed monolayer is found to be nearly independent of the number of
      dipoles. In the case of weak dipolar interactions, our experimental results
      indicate that the bilayer formation is governed by short-range steric and
      electrostatic repulsion, whereas for strong dipolar interactions the bilayer
      formation is governed by long-range dipolar repulsion.

PMID- 16089794
TI  - Ordering and melting in colloidal molecular crystal mixtures.
AB  - We show in simulations that a rich variety of interesting orderings such as
      pinwheel and star states can be realized for colloidal molecular crystal mixtures
      at rational ratios of the number of colloids to the number of minima from an
      underlying periodic substrate. These states can have multistep melting
      transitions and also show coexistence in which one species disorders while the
      other species remains orientationally ordered. For other mixtures, only partially
      ordered or frustrated states form.

PMID- 16089795
TI  - Paranematic interaction between nanoparticles of ordinary shape.
AB  - We propose a general approach to the description of the long-ranged interaction
      between nanoparticles (1-10 nm) of ordinary shape in the paranematic phase, i.e.,
      nematic liquid crystal in the isotropic phase. In general case interaction
      potential is attractive of Yukawa form with derivatives. But it can be
      anisotropic despite the isotropy of the paranematic phase. The origin of such
      anisotropy is the shape of nanoparticles. Particular potentials for spherical and
      cylindrical particles are considered. For the case of nanocylinders anisotropic
      part of the interaction potential can lead to the orientational ordering of them
      in the isotropic phase of nematic liquid crystals.

PMID- 16089796
TI  - Radial compression elasticity of single DNA molecules studied by vibrating
      scanning polarization force microscopy.
AB  - The radial compression properties of single DNA molecules have been studied using
      vibrating scanning polarization force microscopy. By imaging DNA molecules at
      different vibration amplitude set-point values, we obtain the correlations
      between radially applied force and DNA compression, from which the radial
      compressive elasticity can be deduced. The estimated elastic modulus is
      approximately 20-70 MPa under small external forces (<0.4 nN) and increases to
      approximately 100-200 MPa for large loads.

PMID- 16089797
TI  - Multiscale multifractality analysis of a 12-lead electrocardiogram.
AB  - This paper proposes that a multiscale multifractality (MSMF) method be adopted
      for the spatiotemporal analysis of 12-lead ECG. By using this method, the authors
      find that, in some frequency range, 12-lead ECG has a more complex fractal
      structure, and the position of the largest singularity strength range delta alpha
      is not relying on the data length but on the scale factor. By determining the
      inflexion, the MSMF proves to be more sensitive in displaying the trend that the
      singularity strength range delta alpha of human ECG decreases with human aging.

PMID- 16089798
TI  - Thermally induced suppression of friction at the atomic scale.
AB  - Atomic-scale friction, as accessed in tip-based experiments, is investigated
      theoretically in the full range of surface corrugations, temperatures, and
      velocities. Emphasis is given to the regime of thermal drift, when the regular
      stick-slip behavior is completely ruined by thermal effects. The possibility of
      nearly vanishing friction ("thermolubricity") is predicted even for strong
      (overcritical) surface corrugations, when traditional models would predict
      significant friction. The manifestation of this effect in recently published
      experimental data is demonstrated.

PMID- 16089799
TI  - Fluctuation-dissipation relation and the Edwards entropy for a glassy granular
      compaction model.
AB  - We analytically study a one-dimensional compaction model in the glassy regime.
      Both correlation and response functions are calculated exactly in the evolving
      dense and low tapping strength limit, where the density relaxes in a 1/ln t
      fashion. The response and correlation functions turn out to be connected through
      a nonequilibrium generalization of the fluctuation-dissipation theorem. The
      initial response in the average density to an increase in the tapping strength is
      shown to be negative, while on longer time scales it is shown to be positive. On
      short time scales the fluctuation-dissipation theorem governs the relation
      between correlation and response, and we show that such a relationship also
      exists for the slow degrees of freedom, albeit with a different temperature. The
      model is further studied within the statistical theory proposed by Edwards and co
      workers, and the Edwards entropy is calculated in the large system limit. The
      fluctuations described by this approach turn out to match the fluctuations as
      calculated through the dynamical consideration. We thus have an instance where
      these ideas can be confirmed analytically in a non-mean-field model.

PMID- 16089800
TI  - Intensity and coherence of motifs in weighted complex networks.
AB  - The local structure of unweighted networks can be characterized by the number of
      times a subgraph appears in the network. The clustering coefficient, reflecting
      the local configuration of triangles, can be seen as a special case of this
      approach. In this paper we generalize this method for weighted networks. We
      introduce subgraph "intensity" as the geometric mean of its link weights
      "coherence" as the ratio of the geometric to the corresponding arithmetic mean.
      Using these measures, motif scores and clustering coefficient can be generalized
      to weighted networks. To demonstrate these concepts, we apply them to financial
      and metabolic networks and find that inclusion of weights may considerably modify
      the conclusions obtained from the study of unweighted characteristics.

PMID- 16089801
TI  - Violating conformal invariance: two-dimensional clusters grafted to wedges,
      cones, and branch points of Riemann surfaces.
AB  - Lattice animals are one of the few critical models in statistical mechanics
      violating conformal invariance. We present here simulations of two-dimensional
      site animals on square and triangular lattices in nontrivial geometries. The
      simulations are done with the pruned-enriched Rosenbluth method (PERM) algorithm,
      which gives very precise estimates of the partition sum, yielding precise values
      for the entropic exponent theta (Z(N) approximately micro(N)N(-theta)). In
      particular, we studied animals grafted to the tips of wedges with a wide range of
      angles alpha, to the tips of cones (wedges with the sides glued together), and to
      branching points of Riemann surfaces. The latter can either have k sheets and no
      boundary, generalizing in this way cones to angles alpha>360 degrees, or can have
      boundaries, generalizing wedges. We find conformal invariance behavior, theta
      approximately 1/alpha , only for small angles (alpha << 2pi) , while theta
      approximately = const-alpha/2pi for alpha << 2pi. These scalings hold both for
      wedges and cones. A heuristic (nonconformal) argument for the behavior at large
      alpha is given, and comparison is made with critical percolation.

PMID- 16089802
TI  - Jamming in complex gradient networks.
AB  - Flows of physical quantities in large complex networks, natural or man made, rely
      in general on some scalar gradients existing in the networks. We investigate,
      analytically and numerically, under what conditions jamming in gradient flows can
      occur in random and scale-free networks. We find that the degree of jamming
      typically increases with the average connectivity <k> of the network. A crossover
      phenomenon is uncovered where for <k> < k(c) (k(c) denotes a critical
      connectivity, estimated to be about 10), scale-free networks have a higher level
      of congestion than random networks with the same <k>, while the opposite occurs
      for <k> > k(c).

PMID- 16089803
TI  - Devil's-staircase-like behavior of the range of random time series with record
      breaking fluctuations.
AB  - We propose insight into the analysis of the record-breaking fluctuations in
      random time series, which permits to distinguish between the self-organized
      criticality and the record dynamics (RD) scenarios of system evolution, using a
      finite time series realization. Performed analysis of the time series associated
      with the historical prices of different commodities has shown that the evolution
      of commodity markets is controlled by the record-breaking fluctuations as it is
      outlined by the RD. Furthermore, we found that the sizes of record-breaking
      fluctuations follow a fat-tailed distribution and the devil's-staircase-like
      records of price ranges are multiaffine and persistent, nevertheless, the high
      moments (q> q(C) >2) of their q-order height-height correlation functions behave
      logarithmically.

PMID- 16089804
TI  - Phase chaos in coupled oscillators.
AB  - A complex high-dimensional chaotic behavior, phase chaos, is found in the finite
      dimensional Kuramoto model of coupled phase oscillators. This type of chaos is
      characterized by half of the spectrum of Lyapunov exponents being positive and
      the Lyapunov dimension equaling almost the total system dimension. Intriguingly,
      the strongest phase chaos occurs for intermediate-size ensembles. Phase chaos is
      a common property of networks of oscillators of very different natures, such as
      phase oscillators, limit-cycle oscillators, and chaotic oscillators, e.g.,
      Rossler systems.

PMID- 16089805
TI  - Desynchronization of coupled electrochemical oscillators with pulse stimulations.
AB  - Various stimulation desynchronization techniques are explored in a laboratory
      experiment on electrochemical oscillators, a system that exhibits transient
      dynamics, heterogeneities, and inherent noise. Stimulation with a short, single
      pulse applied at a vulnerable phase can effectively desynchronize a cluster. A
      double pulse method, that can be applied at any phase, can be improved either by
      adding an extra weak pulse between the original two pulses or by adding noise to
      the first pulse.

PMID- 16089806
TI  - Chaos synchronization in gap-junction-coupled neurons.
AB  - Depending on temperature, the modified Hodgkin-Huxley (MHH) equations exhibit a
      variety of dynamical behaviors, including intrinsic chaotic firing. We analyze
      synchronization in a large ensemble of MHH neurons that are interconnected with
      gap junctions. By evaluating tangential Lyapunov exponents we clarify whether the
      synchronous state of neurons is chaotic or periodic. Then, we evaluate
      transversal Lyapunov exponents to elucidate if this synchronous state is stable
      against infinitesimal perturbations. Our analysis elucidates that with weak gap
      junctions, the stability of the synchronization of MHH neurons shows rather
      complicated changes with temperature. We, however, find that with strong gap
      junctions, the synchronous state is stable over the wide range of temperature
      irrespective of whether synchronous state is chaotic or periodic. It turns out
      that strong gap junctions realize the robust synchronization mechanism, which
      well explains synchronization in interneurons in the real nervous system.

PMID- 16089807
TI  - Mode selection in the spontaneous motion of an alcohol droplet.
AB  - An alcohol (pentanol) droplet exhibits spontaneous motion on an aqueous solution,
      driven by a solutal Marangoni effect. We found that the droplets mode of motion
      is controlled by its volume. A droplet with a volume of less than 0.1 microl
      shows irregular translational motion, whereas intermediate-sized droplets of 0.1
      200 microl show vectorial motion. When the volume is above 300 microl, the
      droplet splits into smaller drops. These experimental results regarding mode
      selection are interpreted in terms of the wave-number selection depending on the
      droplet volume.

PMID- 16089808
TI  - Dynamical scaling and intermittency in shell models of turbulence.
AB  - We introduce a model for the turbulent energy cascade aimed at studying the
      effect of dynamical scaling on intermittency. In particular, we show that by
      slowing down the energy-transfer mechanism for fixed energy flux, intermittency
      decreases and eventually disappears. This result supports the conjecture that
      intermittency can be observed only if energy is flowing towards faster and faster
      scales of motion.

PMID- 16089809
TI  - Multifractal eigenstates of quantum chaos and the Thue-Morse sequence.
AB  - We analyze certain eigenstates of the quantum baker's map and demonstrate, using
      the Walsh-Hadamard transform, the emergence of the ubiquitous Thue-Morse
      sequence, a simple sequence that is at the border between quasiperiodicity and
      chaos, and hence is a good paradigm for quantum chaotic states. We show a family
      of states that are also simply related to the Thue-Morse sequence and are
      strongly scarred by short periodic orbits and their homoclinic excursions. We
      give approximate expressions for these states and provide evidence that these and
      other generic states are multifractal.

PMID- 16089810
TI  - Self-channeling of ultrashort laser pulses in materials with anomalous
      dispersion.
AB  - The nonlinear dynamics of femtosecond optical pulses propagating in solid media
      with anomalous group-velocity dispersion (GVD) is investigated. A map fixing the
      boundaries of collapse or noncollapse regimes for high-power beams versus the
      relative strength of GVD is first established. Next, from a nonlinear Schrodinger
      model accounting for higher-order dispersion, self-steepening, and plasma
      generation, the possibility of producing extended collapse events that promote a
      long self-guiding is confirmed, in agreement with recent experiments [K.D. Moll
      and A.L. Gaeta, Opt. Lett. 29, 995 (2004)]. Three-dimensional collapsing pulses
      are shown to propagate by emitting quasiperiodically bursts of temporally
      compressed light bullets, with durations close to the single cycle limit.

PMID- 16089811
TI  - Coherence resonance in an atmospheric global circulation model.
AB  - Numerical evidence is presented of a coherence-resonant behavior, induced on an
      atmospheric global circulation model by a white (in time and space) additive
      Gaussian noise with amplitude A << 1 . Intermediate A values enhance the
      spatiotemporal regularity of vortical patterns that contribute to the intra
      annual variability of the atmospheric component of the climate. Only weak
      patterns (those appearing in the summer hemisphere) become ordered by noise.

PMID- 16089812
TI  - Stable vortex solitons in nonlocal self-focusing nonlinear media.
AB  - We reveal that spatially localized vortex solitons become stable in self-focusing
      nonlinear media when the vortex symmetry-breaking azimuthal instability is
      eliminated by a nonlocal nonlinear response. We study the main properties of
      different types of vortex beams and discuss the physical mechanism of the vortex
      stabilization in spatially nonlocal nonlinear media.

PMID- 16089813
TI  - Phase behavior of a three-dimensional core-softened model system.
AB  - The phase behavior of a three-dimensional model substance interacting via a
      continuous core-softened pair potential is studied. A combination of
      thermodynamic integration and free-energy augmented metadynamics is employed to
      identify the ground state structure as simple hexagonal. A transition to close
      packing is predicted at high pressure. The melting line is traced, which when
      combined with the liquid-vapor line, allows the liquid to be studied over its
      entire thermodynamically stable range. We find no liquid anomalies in the range
      of pressures for which the vaporization transition exists. Our results therefore
      support suggestions that the anomalous behavior of such fluids is unique to the
      two-dimensional case.

PMID- 16089814
TI  - Biased random satisfiability problems: from easy to hard instances.
AB  - In this paper we study biased random K -satisfiability ( K -SAT) problems in
      which each logical variable is negated with probability p . This generalization
      provides us a crossover from easy to hard problems and would help us in a better
      understanding of the typical complexity of random K -SAT problems. The exact
      solution of 1-SAT case is given. The critical point of K -SAT problems and
      results of replica method are derived in the replica symmetry framework. It is
      found that in this approximation alpha(c) proportional p(-(K-1)) for p --> 0.
      Solving numerically the survey propagation equations for K = 3 we find that for p
      < p* approximately 0.17 there is no replica symmetry breaking and still the SAT
      UNSAT transition is discontinuous.

PMID- 16089815
TI  - Fluctuations of work from quantum subensembles: the case against quantum work
      fluctuation theorems.
AB  - We study how Thomson's formulation of the second law of thermodynamics (no work
      is extracted from an equilibrium ensemble by a cyclic process) emerges in the
      quantum situation through the averaging over fluctuations of work. The latter
      concept is carefully defined for an ensemble of quantum systems, the members of
      which interact with macroscopic sources of work. The approach is based on
      splitting a mixed quantum ensemble into pure subensembles, which according to
      quantum mechanics are maximally complete and irreducible. The splitting is done
      by filtering the outcomes of a measurement process. The approach is corroborated
      by comparing to relevant experiments in quantum optics. A critical review is
      given of two other approaches to fluctuations of work proposed in the literature.
      It is shown that in contrast to those, the present definition (i) is consistent
      with the physical meaning of the concept of work as mechanical energy lost by the
      macroscopic sources, or, equivalently, as the average energy acquired by the
      ensemble; (ii) applies to an arbitrary nonequilibrium state. There is no direct
      generalization of the classical work-fluctuation theorem to the proper quantum
      domain. This implies nonclassical scenarios for the emergence of the second law.

PMID- 16089816
TI  - Effects of diversity on multiagent systems: minority games.
AB  - We consider a version of large population games whose agents compete for
      resources using strategies with adaptable preferences. The games can be used to
      model economic markets, ecosystems, or distributed control. Diversity of initial
      preferences of strategies is introduced by randomly assigning biases to the
      strategies of different agents. We find that diversity among the agents reduces
      their maladaptive behavior. We find interesting scaling relations with diversity
      for the variance and other parameters such as the convergence time, the fraction
      of fickle agents, and the variance of wealth, illustrating their dynamical
      origin. When diversity increases, the scaling dynamics is modified by kinetic
      sampling and waiting effects. Analyses yield excellent agreement with
      simulations.

PMID- 16089817
TI  - Quantum approach to nucleation times of kinetic Ising ferromagnets.
AB  - Low temperature dynamics of Ising ferromagnets under finite magnetic fields are
      studied in terms of quantum spin representations of stochastic evolution
      operators. These are constructed for the Glauber dynamic as well as for its
      modification, introduced by Park [Phys. Rev. Lett. 92, 015701 (2004)]. In both
      cases the relaxation time after a field quench is evaluated both numerically and
      analytically using the spectrum gap of the corresponding operators. The numerical
      work employs standard recursive techniques following a symmetrization of the
      evolution operator accomplished by a nonunitary spin rotation. The analytical
      approach uses low temperature limits to identify dominant terms in the eigenvalue
      problem. It is argued that the relaxation times already provide a measure of
      actual nucleation lifetimes under finite fields. The approach is applied to
      square, triangular and honeycomb lattices.

PMID- 16089818
TI  - Cluster formation in the system of interacting Bose particles.
AB  - Based on statistical approach we described possible formation of spatially
      inhomogeneous distribution in the system of interacting Bose particles. The
      condition of cluster formation in both gas and condensed phases was obtained in
      this system. We studied the dynamics of cluster formation in the limit case of
      high temperatures. We compared the cluster-formation processes in the attractive
      system (with short-range interaction) and in the gravitational system at the low
      temperatures of Bose-Einstein condensate regime.

PMID- 16089819
TI  - Statistical properties of fracture in a random spring model.
AB  - Using large-scale numerical simulations, we analyze the statistical properties of
      fracture in the two-dimensional random spring model and compare it with its
      scalar counterpart: the random fuse model. We first consider the process of crack
      localization measuring the evolution of damage as the external load is raised. We
      find that, as in the fuse model, damage is initially uniform and localizes at
      peak load. Scaling laws for the damage density, fracture strength, and avalanche
      distributions follow with slight variations the behavior observed in the random
      fuse model. We thus conclude that scalar models provide a faithful representation
      of the fracture properties of disordered systems.

PMID- 16089820
TI  - Comparison of voter and Glauber ordering dynamics on networks.
AB  - We study numerically the ordering process of two very simple dynamical models for
      a two-state variable on several topologies with increasing levels of
      heterogeneity in the degree distribution. We find that the zero-temperature
      Glauber dynamics for the Ising model may get trapped in sets of partially ordered
      metastable states even for finite system size, and this becomes more probable as
      the size increases. Voter dynamics instead always converges to full order on
      finite networks, even if this does not occur via coherent growth of domains. The
      time needed for order to be reached diverges with the system size. In both cases
      the ordering process is rather insensitive to the variation of the degree
      distribution from sharply peaked to scale free.

PMID- 16089821
TI  - Phase transition in a directed traffic flow network.
AB  - The generic feature of traffic in a network of flowing electronic data packets is
      a phase transition from a stationary free-flow phase to a continuously growing
      congested nonstationary phase. In the most simple network of directed oriented
      square lattice we have been able to observe all crucial features of such flow
      systems having nontrivial critical behavior near the critical point of
      transition. The network here is in the shape of a square lattice and data packets
      are randomly posted with a rate rho at one side of the lattice. Each packet
      executes a directed diffusive motion toward the opposite boundary where it is
      delivered. Packets accumulated at a particular node form a queue and a maximum of
      m such packets randomly jump out of this node at every time step to its neighbors
      on a first-in-first-out basis. The phase transition occurs at rho(c) = m. The
      distribution of travel times through the system is found to have a log-normal
      behavior and the power spectrum of the load time series shows 1/f-like noise
      similar to the scenario of Internet traffic.

PMID- 16089822
TI  - Correlation function and generalized master equation of arbitrary age.
AB  - We study a two-state statistical process with a non-Poisson distribution of
      sojourn times. In accordance with earlier work, we find that this process is
      characterized by aging and we study three different ways to define the
      correlation function of arbitrary age of the corresponding dichotomous
      fluctuation. These three methods yield exact expressions, thus coinciding with
      the recent result by Godreche and Luck [J. Stat. Phys. 104, 489 (2001)].
      Actually, non-Poisson statistics yields infinite memory at the probability level,
      thereby breaking any form of Markovian approximation, including the one adopted
      herein, to find an approximated analytical formula. For this reason, we check the
      accuracy of this approximated formula by comparing it with the numerical
      treatment of the second of the three exact expressions. We find that, although
      not exact, a simple analytical expression for the correlation function of
      arbitrary age is very accurate. We establish a connection between the correlation
      function and a generalized master equation of the same age. Thus this formalism,
      related to models used in glassy materials, allows us to illustrate an approach
      to the statistical treatment of blinking quantum dots, bypassing the limitations
      of the conventional Liouville treatment.

PMID- 16089823
TI  - Aliasing in 1/f(alpha) noise spectra: origins, consequences, and remedies.
AB  - The scaling exponent of a 1/f(alpha) noise time series is commonly estimated from
      the power-law slope of its Fourier power spectrum. Here I show that because
      1/f(alpha) noises typically have significant power above the Nyquist frequency,
      measurements of their power spectra will often be severely distorted by aliasing,
      not only near the Nyquist frequency, but also far below it. I show that spectral
      aliasing typically leads to large systematic biases in the scaling exponents, and
      thus the fractal dimensions, that are estimated from the power-law slopes of
      1/f(alpha) noise spectra. I describe a simple spectral filtering method that
      corrects the distortions introduced by spectral aliasing, and recovers the
      broadband spectrum of 1/f(alpha) noises. Like a Wiener filter, this filtering
      method does not require that the correct spectrum is known in advance. I
      illustrate this filtering technique using two environmental noise spectra that
      are distorted by aliasing.

PMID- 16089824
TI  - Navigating networks with limited information.
AB  - We study navigation with limited information in networks and demonstrate that
      many real-world networks have a structure which can be described as favoring
      communication at short distance at the cost of constraining communication at long
      distance. This feature, which is robust and more evident with limited than with
      complete information, reflects both topological and possibly functional design
      characteristics. For example, the characteristics of the networks studied derived
      from a city and from the Internet are manifested through modular network designs.
      We also observe that directed navigation in typical networks requires remarkably
      little information on the level of individual nodes. By studying navigation or
      specific signaling, we take a complementary approach to the common studies of
      information transfer devoted to broadcasting of information in studies of virus
      spreading and the like.

PMID- 16089825
TI  - Coexisting phases and lattice dependence of a cellular automaton model for
      traffic flow.
AB  - The Biham-Middleton-Levine traffic model is perhaps the simplest system
      exhibiting phase transitions and self-organization. Moreover, it is an
      underpinning to extensive modern studies of traffic flow. The general belief is
      that the system exhibits a sharp phase transition from freely flowing to fully
      jammed, as a function of initial density of cars. However, we discover
      intermediate stable phases, where jams and freely flowing traffic coexist. The
      geometric structure of such phases is highly regular, with bands of free flowing
      traffic intersecting at jammed wave fronts that propagate smoothly through the
      space. Instead of a phase transition as a function of density, we see bifurcation
      points, where intermediate phases begin coexisting with the more conventionally
      known phases. We show that the regular geometric structure is in part a
      consequence of the finite size and aspect ratio of the underlying lattice, and
      that for certain aspect ratios the asymptotic intermediate phase is on a periodic
      limit cycle (the exact microscopic configuration recurs each tau time steps).
      Aside from describing these intermediate states, which previously were
      overlooked, we derive simple equations to describe the geometric constraints, and
      predict their asymptotic velocities.

PMID- 16089826
TI  - Absorbing-state phase transitions with extremal dynamics.
AB  - Extremal dynamics represents a path to self-organized criticality in which the
      order parameter is tuned to a value of zero. The order parameter is associated
      with a phase transition to an absorbing state. Given a process that exhibits a
      phase transition to an absorbing state, we define an "extremal absorbing"
      process, providing the link to the associated extremal (nonabsorbing) process.
      Stationary properties of the latter correspond to those at the absorbing-state
      phase transition in the former. Studying the absorbing version of an extremal
      dynamics model allows to determine certain critical exponents that are not
      otherwise accessible. In the case of the Bak-Sneppen (BS) model, the absorbing
      version is closely related to the "f -avalanche" introduced by Paczuski, Maslov,
      and Bak [Phys. Rev. E 53, 414 (1996)], or, in spreading simulations to the "BS
      branching process" also studied by these authors. The corresponding nonextremal
      process belongs to the directed percolation universality class. We revisit the
      absorbing BS model, obtaining refined estimates for the threshold and critical
      exponents in one dimension. We also study an extremal version of the usual
      contact process, using mean-field theory and simulation. The extremal condition
      slows the spread of activity and modifies the critical behavior radically,
      defining an "extremal directed percolation" universality class of absorbing-state
      phase transitions. Asymmetric updating is a relevant perturbation for this class,
      even though it is irrelevant for the corresponding nonextremal class.

PMID- 16089827
TI  - Fermi-Dirac statistics and traffic in complex networks.
AB  - We propose an idealized model for traffic in a network, in which many particles
      move randomly from node to node, following the network's links, and it is assumed
      that at most one particle can occupy any given node. This is intended to mimic
      the finite forwarding capacity of nodes in communication networks, thereby
      allowing the possibility of congestion and jamming phenomena. We show that the
      particles behave like free fermions, with appropriately defined energy-level
      structure and temperature. The statistical properties of this system are thus
      given by the corresponding Fermi-Dirac distribution. We use this to obtain
      analytical expressions for dynamical quantities of interest, such as the mean
      occupation of each node and the transport efficiency, for different network
      topologies and particle densities. We show that the subnetwork of free nodes
      always fragments into small isolated clusters for a sufficiently large number of
      particles, implying a communication breakdown at some density for all network
      topologies. These results are compared to direct simulations.

PMID- 16089828
TI  - Damage spreading in two-dimensional trivalent cellular structures with competing
      Glauber and Kawasaki dynamics.
AB  - The damage spreading of the Ising model on several two-dimensional trivalent
      structures, including soap froth, Voronoi, and hierarchical structures, are
      studied with competing Glauber and Kawasaki dynamics. The damage spreading
      transition temperature T(d) and the Curie temperature T(C) of these structures
      are compared. We find that T(d) of the hierarchical lattices decreases sharply as
      the probability of occurrence of Kawasaki dynamics increases, whereas for soap
      froth and Voronoi, T(d) for the Voronoi and soap froth remain nearly unchanged
      except when the dynamics is dominated by Kawasaki dynamics. T(d) and T(C) in our
      two-dimensional structures are nearly the same and they behave similarly as we
      change the relative probability of occurrence of the Glauber and Kawasaki
      dynamics. A heuristic argument is provided to explain the numerical results.

PMID- 16089829
TI  - Loops structure of the Internet at the autonomous system level.
AB  - We present here a study of the clustering and loops in a graph of the Internet at
      the autonomous systems level. We show that, even if the whole structure is
      changing with time, the statistical distributions of loops of order 3, 4, and 5
      remain stable during the evolution. Moreover, we will bring evidence that the
      Internet graphs show characteristic Markovian signatures, since the structure is
      very well described by two-point correlations between the degrees of the
      vertices. This indeed proves that the Internet belongs to a class of network in
      which the two-point correlation is sufficient to describe their whole local (and
      thus global) structure. Data are also compared to present Internet models.

PMID- 16089830
TI  - Quasiparticles in a thermal process.
AB  - We introduce an abstract scalar field and a covariant field equation, by which we
      make an attempt to connect the Fourier heat conduction and wave-like heat
      propagation. This field can be the generalization of the usual temperature from a
      dynamical point of view. It is shown that a kind of effective mass of this
      thermal process can be calculated. Finally, we express the unit of dissipative
      action with the help of universal constants.

PMID- 16089831
TI  - Inverse cascade in a percolation model: hierarchical description of time
      dependent scaling.
AB  - The dynamics of a two-dimensional site percolation model on a square lattice is
      studied using the hierarchical approach introduced by Gabrielov [Phys. Rev. E 60,
      5293 (1999)]. The key elements of the approach are the tree representation of
      clusters and their coalescence, and the Horton-Strahler scheme for cluster
      ranking. Accordingly, the evolution of the percolation model is considered as a
      hierarchical inverse cascade of cluster aggregation. A three-exponent time
      dependent scaling for the cluster rank distribution is derived using the Tokunaga
      branching constraint and classical results on percolation in terms of cluster
      masses. Deviations from the pure scaling are described. An empirical constraint
      on the dynamics of a rank population is reported based on numerical simulations.

PMID- 16089832
TI  - Stabilization analysis and modified Korteweg-de Vries equation in a cooperative
      driving system.
AB  - Two lattice traffic models are proposed by incorporating a cooperative driving
      system. The lattice versions of the hydrodynamic model of traffic flow are
      described by the differential-difference equation and difference-difference
      equation, respectively. The stability conditions for the two models are obtained
      using the linear stability theory. The results show that considering more than
      one site ahead in vehicle motion leads to the stabilization of the system. The
      modified Korteweg-de Vries equation (the mKdV equation, for short) near the
      critical point is derived by using the reductive perturbation method to show the
      traffic jam which is proved to be described by kink-anti-kink soliton solutions
      obtained from the mKdV equations.

PMID- 16089833
TI  - Memory is relevant in the symmetric phase of the minority game.
AB  - Minority game is a simple-mined econophysical model capturing the cooperative
      behavior among selfish players. Previous investigations, which were based on
      numerical simulations up to about 100 players for a certain parameter alpha in
      the range 0.1 < approximately alpha < approximately 1, suggested that memory is
      irrelevant to the cooperative behavior of the minority game in the so-called
      symmetric phase. Here using a large scale numerical simulation up to about 3000
      players in the parameter range 0.01 < approximately alpha < approximately 1, we
      show that the mean variance of the attendance in the minority game actually
      depends on the memory in the symmetric phase. We explain such dependence in the
      framework of crowd-anticrowd theory. Our findings conclude that one should not
      overlook the feedback mechanism buried under the correlation in the history time
      series in the study of minority game.

PMID- 16089834
TI  - Anisotropy in rupture lines of paper sheets.
AB  - We have experimentally investigated the fracture process in paper samples
      submitted to a uniaxial force. Five types of paper sheets (newsprint, towel,
      sulfite, silk, and couche papers) were fractured along two orthogonal
      orientations. In order to characterize the rupture lines of the paper sheets we
      utilized the Hurst exponent. Our results indicate a dependence of the Hurst
      exponent on the orientation of the paper sheets for samples of newsprint and,
      probably, towel and silk papers. For the other types of paper the Hurst exponent
      does not depend on the direction of crack propagation.

PMID- 16089835
TI  - Theory for long memory in supply and demand.
AB  - Recent empirical studies have demonstrated long-memory in the signs of orders to
      buy or sell in financial markets [J.-P. Bouchaud, Y. Gefen, M. Potters, and M.
      Wyart, Quant. Finance 4, 176 (2004); F. Lillo and J. D. Farmer Dyn. Syst. Appl.
      8, 3 (2004)]. We show how this can be caused by delays in market clearing. Under
      the common practice of order splitting, large orders are broken up into pieces
      and executed incrementally. If the size of such large orders is power-law
      distributed, this gives rise to power-law decaying autocorrelations in the signs
      of executed orders. More specifically, we show that if the cumulative
      distribution of large orders of volume v is proportional to v(-alpha) and the
      size of executed orders is constant, the autocorrelation of order signs as a
      function of the lag tau is asymptotically proportional to tau(-(alpha-1)). This
      is a long-memory process when alpha < 2. With a few caveats, this gives a good
      match to the data. A version of the model also shows long-memory fluctuations in
      order execution rates, which may be relevant for explaining the long memory of
      price diffusion rates.

PMID- 16089836
TI  - Monitoring of a preseismic phase from its electromagnetic precursors.
AB  - Fracture in disordered media is a complex problem for which a definitive physical
      and theoretical treatment is still lacking. We view earthquakes (EQ's) as large
      scale fracture phenomena in the Earth's heterogeneous crust. Our main
      observational tool is the monitoring of the microfractures, which occur in the
      prefocal area before the final breakup, by recording their kHz-MHz
      electromagnetic (EM) emissions, with the MHz radiation appearing earlier than the
      kHz. Two fundamental questions (unanswered yet) that scientists in this field
      ought to address are as follows. (i) Is there a way of estimating the time to
      global failure? (ii) Is the evolution towards global failure irreversible after
      the appearance of distinguishing features in the preseismic EM time series? We
      attempt to put forward physically powerful arguments with regard to answering
      these two basic questions. Our approach will be in terms of critical phase
      transitions in statistical physics, drawing on recently published results. We
      obtain two major results. First, the initial MHz part of the preseismic emission,
      which has anti-persistent behavior, is triggered by microfractures in the highly
      disordered system that surrounds the essentially homogeneous "backbone
      asperities" within the prefocal area and could be described in analogy with a
      thermal continuous phase transition. However, the analysis reveals that the
      system is gradually driven out of equilibrium. Considerations of the symmetry
      breaking and "intermittent dynamics of critical fluctuations" method estimate the
      time beyond which the process generating the preseismic EM emission could
      continue only as a nonequilibrium instability. Second, the abrupt emergence of
      strong kHz emission in the tail of the precursory radiation, showing strong
      persistent behavior, is thought to be due to the fracture of the high-strength
      "backbones". The associated phase of the EQ nucleation is a nonequilibrium
      process without any footprint of an equilibrium thermal phase transition. The
      family of asperities sustains the system. Physically, the appearance of
      persistent properties may indicate that the process acquires a self-regulating
      character and to a great degree the property of irreversibility, one of the
      important components of predictive capability. We address the role of the order
      of material heterogeneity on the transition from anti-persistent to persistent
      behavior.

PMID- 16089837
TI  - Generating structured networks based on a weight-dependent deactivation
      mechanism.
AB  - Motivated by the degree-dependent deactivation model generating networks with
      high clustering coefficient [K. Klemm, Phys. Rev. E. 65, 036123 (2002)], a weight
      dependent version is studied to model evolving networks. The growth dynamics of
      the network is based on a naive weight-driven deactivation mechanism which
      couples the establishment of new active vertices and the weights' dynamical
      evolution. Both analytical solutions and numerical simulations show that the
      generated networks possess a high clustering coefficient larger than that for
      regular lattices of the same average connectivity. Weighted, structured scale
      free networks are obtained as the deactivated vertex is target selected at each
      time step, and weighted, structured exponential networks are realized for the
      random-selected case.

PMID- 16089838
TI  - Adiabatic molecular-dynamics-simulation-method studies of kinetic friction.
AB  - An adiabatic molecular-dynamics method is developed and used to study the Muser
      Robbins model for dry friction (i.e., nonzero kinetic friction in the slow
      sliding speed limit). In this model, dry friction between two crystalline
      surfaces rotated with respect to each other is due to mobile molecules (i.e.,
      dirt particles) adsorbed at the interface. Our adiabatic method allows us to
      quickly locate interface potential-well minima, which become unstable during
      sliding of the surfaces. Since dissipation due to friction in the slow sliding
      speed limit results from mobile molecules dropping out of such unstable wells,
      our method provides a way to calculate dry friction, which agrees extremely well
      with results found by conventional molecular dynamics for the same system, but
      our method is more than a factor of 10 faster.

PMID- 16089839
TI  - Liquid-vapor interface of a polydisperse fluid.
AB  - We report a grand canonical Monte Carlo simulation study of the liquid-vapor
      interface of a model fluid exhibiting polydispersity in terms of the particle
      size sigma. The bulk density distribution, rho0(sigma), of the system is
      controlled by the imposed chemical potential distribution mu(sigma), the form of
      which is specified such that rho0(sigma) assumes a Schulz form with associated
      degree of polydispersity approximately = 14%. By introducing a smooth attractive
      wall, a planar liquid-vapor interface is formed for bulk state points within the
      region of liquid-vapor coexistence. Owing to fractionation, the pure liquid phase
      is enriched in large particles, with respect to the coexisting vapor. We
      investigate how the spatial variation of the density near the liquid-vapor
      interface affects the evolution of the local distribution of particle sizes
      between the limiting pure phase forms. We find [as previously predicted by
      density-functional theory, Bellier-Castella, Phys. Rev. E 65, 021503 (2002)] a
      segregation of smaller particles to the interface. The magnitude of this effect
      as a function of sigma is quantified via measurements of the relative adsorption.
      Additionally, we consider the utility of various estimators for the interfacial
      width and highlight the difficulty of isolating the intrinsic contribution of
      polydispersity to this width.

PMID- 16089840
TI  - Void formation and roughening in slow fracture.
AB  - Slow crack propagation in ductile, and in certain brittle materials, appears to
      take place via the nucleation of voids ahead of the crack tip due to plastic
      yields, followed by the coalescence of these voids. Postmortem analysis of the
      resulting fracture surfaces of ductile and brittle materials on the microm-mm and
      the nm scales, respectively, reveals self-affine cracks with anomalous scaling
      exponent zeta approximately = 0.8 in 3 dimensions and zeta approximately = 0.65
      in 2 dimensions. In this paper we present an analytic theory based on the method
      of iterated conformal maps aimed at modelling the void formation and the fracture
      growth, culminating in estimates of the roughening exponents in 2 dimensions. In
      the simplest realization of the model we allow one void ahead of the crack, and
      address the robustness of the roughening exponent. Next we develop the theory
      further, to include two voids ahead of the crack. This development necessitates
      generalizing the method of iterated conformal maps to include doubly connected
      regions (maps from the annulus rather than the unit circle). While mathematically
      and numerically feasible, we find that the employment of the stress field as
      computed from elasticity theory becomes questionable when more than one void is
      explicitly inserted into the material. Thus further progress in this line of
      research calls for improved treatment of the plastic dynamics.

PMID- 16089841
TI  - Cluster mean-field study of the parity-conserving phase transition.
AB  - The phase transition of the branching and annihilating random walk with even
      offspring is studied by N-cluster mean-field approximations on one-dimensional
      lattices. By allowing the system to reach zero branching rate a phase transition
      can be seen for any N < or = 12. Coherent anomaly extrapolations applied for the
      series of approximations results in nu(perpendicular) = 1.85(3) and beta=0.96(2).

PMID- 16089842
TI  - Absorbing phase transition with a conserved field.
AB  - We study a lattice gas model where the number of particles is conserved during
      dynamical process. Our model shows a continuous phase transition from a
      fluctuating phase to two symmetric absorbing states at the critical point in one
      dimension. We conjecture the values of the critical exponents characterizing the
      phase transition of our model. We show that the obtained values are in good
      agreement with those estimated from computer simulations. The critical exponents
      indicate that our model exhibits an absorbing phase transition which is different
      from the known ones.

PMID- 16089843
TI  - Bifurcations in reaction-diffusion systems in chaotic flows.
AB  - We study the behavior of reacting tracers in a chaotic flow. In particular, we
      look at an autocatalytic reaction and at a bistable system which are subjected to
      stirring by a chaotic flow. The impact of the chaotic advection is described by a
      one-dimensional phenomenological model. We use a nonperturbative technique to
      describe the behavior near a saddle node bifurcation. We also find an
      approximation of the solution far away from the bifurcation point. The results
      are confirmed by numerical simulations and show good agreement.

PMID- 16089844
TI  - Noise-induced spatiotemporal dynamics in a linear array of excitable chemical
      oscillators.
AB  - The effects of additive noise on spatiotemporal dynamics are investigated in a
      one-dimensional array of excitable elements in which the Belousov-Zhabotinsky
      reaction is localized. At the appropriate separation between adjacent elements,
      we find that the resonance effect becomes larger for the element being more apart
      from the first element when only the first element is subjected to the external
      noise. This phenomenon is a sort of array-enhanced resonance. Furthermore, we
      find that phase locking between the first element and the other elements is
      induced via coherence resonance of the first element. Experimental observations
      are approximately reproduced in a numerical simulation with a forced Oregonator
      reaction-diffusion model.

PMID- 16089845
TI  - Uniform semiclassical approach to fidelity decay: from weak to strong
      perturbation.
AB  - We study fidelity decay by a uniform semiclassical approach, in the three
      perturbation regimes: namely, the perturbative regime, the Fermi golden rule
      (FGR) regime, and the Lyapunov regime. A semiclassical expression is derived for
      the fidelity of initial Gaussian wave packets with width of the order sqare root
      h (h being the effective Planck constant). The short-time decay of the fidelity
      of initial Gaussian wave packets is also studied with respect to two time scales
      introduced in the semiclassical approach. In the perturbative regime, it is
      confirmed numerically that fidelity has FGR-type decay before Gaussian decay sets
      in. An explanation is suggested for a non-FGR decay in the FGR regime of a system
      with weak chaos in the classical limit by using the Levy distribution as an
      approximation for the distribution of the action difference. In the Lyapunov
      regime, it is shown that the average of the logarithm of fidelity may have
      roughly Lyapunov decay within some time interval in systems possessing large
      fluctuations in the finite-time Lyapunov exponent in the classical limit.

PMID- 16089846
TI  - Bubble, stripe, and ring phases in a two-dimensional cluster with competing
      interactions.
AB  - A system of classical charged particles confined in a two-dimensional trap and
      interacting through a competing short-range attraction and long-range repulsion
      potential is studied. The structure of the system strongly depends on the
      interaction range of the short-range attraction potential and the total number of
      particles. Depending on the appropriate choice of parameters for the attractive
      potential, the particles organize themselves in bubbles, stripe phases, and
      ringlike configurations, or combinations of both of them. Detailed phase diagrams
      are presented for systems consisting of N=2 up to N=6 particles. General rules
      are derived for the different subsequent transitions between those configurations
      and how the ground state configuration of a large system can be deduced from the
      one of a small number of particles.

PMID- 16089847
TI  - Discrete time model for chemical or biological decay in chaotic flows: reentrance
      phase transitions.
AB  - We consider a discrete time model of advection, reaction, and diffusion on a
      lattice to investigate the steady-state spatial structure of chemically decaying
      substances. The time discretization of the dynamics has a considerable impact on
      these structures. Additional smooth-filamental phase transitions, nonexistent in
      the continuous-time description, appear. We show how these structures and their
      scaling properties depend on the time step of the discrete dynamics. Exploiting
      the analogies of this discrete model with the logistic map, some general features
      are discussed.

PMID- 16089848
TI  - Symmetry breaking in a driven and strongly damped pendulum.
AB  - We examine the conditions for appearance of a symmetry breaking bifurcation in
      damped and periodically driven pendulums in the case of strong damping. We show
      that symmetry breaking, unlike other nonlinear phenomena, can exist at high
      dissipation. We prove that symmetry breaking phases exist between phases of
      symmetric normal and symmetric inverted oscillations. We find that symmetry
      broken solutions occupy a smaller region of the pendulum's parameter space in
      comparison to the statements made in earlier considerations [McDonald and
      Plischke, Phys. Rev. B 27, 201 (1983)]. Our research on symmetry breaking in a
      strongly damped pendulum is relevant to an understanding of the phenomena of
      dynamic symmetry breaking and rectification in pure ac driven semiconductor
      superlattices.

PMID- 16089849
TI  - Nonextensive random matrix theory approach to mixed regular-chaotic dynamics.
AB  - We apply Tsallis' q -indexed entropy to formulate a nonextensive random matrix
      theory, which may be suitable for systems with mixed regular-chaotic dynamics.
      The joint distribution of the matrix elements is given by folding the
      corresponding quantity in the conventional random matrix theory by a distribution
      of the inverse matrix-element variance. It keeps the basis invariance of the
      standard theory but violates the independence of the matrix elements. We consider
      the subextensive regime of q more than unity in which the transition from the
      Wigner to the Poisson statistics is expected to start. We calculate the level
      density for different values of the entropic index. Our results are consistent
      with an analogous calculation by Tsallis and collaborators. We calculate the
      spacing distribution for mixed systems with and without time-reversal symmetry.
      Comparing the result of calculation to a numerical experiment shows that the
      proposed nonextensive model provides a satisfactory description for the initial
      stage of the transition from chaos towards the Poisson statistics.

PMID- 16089850
TI  - Statistical validation of mutual information calculations: comparison of
      alternative numerical algorithms.
AB  - Given two time series X and Y , their mutual information, I (X,Y) = I (Y,X) , is
      the average number of bits of X that can be predicted by measuring Y and vice
      versa. In the analysis of observational data, calculation of mutual information
      occurs in three contexts: identification of nonlinear correlation, determination
      of an optimal sampling interval, particularly when embedding data, and in the
      investigation of causal relationships with directed mutual information. In this
      contribution a minimum description length argument is used to determine the
      optimal number of elements to use when characterizing the distributions of X and
      Y . However, even when using partitions of the X and Y axis indicated by minimum
      description length, mutual information calculations performed with a uniform
      partition of the XY plane can give misleading results. This motivated the
      construction of an algorithm for calculating mutual information that uses an
      adaptive partition. This algorithm also incorporates an explicit test of the
      statistical independence of X and Y in a calculation that returns an assessment
      of the corresponding null hypothesis. The previously published Fraser-Swinney
      algorithm for calculating mutual information includes a sophisticated procedure
      for local adaptive control of the partitioning process. When the Fraser and
      Swinney algorithm and the algorithm constructed here are compared, they give very
      similar numerical results (less than 4% difference in a typical application).
      Detailed comparisons are possible when X and Y are correlated jointly Gaussian
      distributed because an analytic expression for I (X,Y) can be derived for that
      case. Based on these tests, three conclusions can be drawn. First, the algorithm
      constructed here has an advantage over the Fraser-Swinney algorithm in providing
      an explicit calculation of the probability of the null hypothesis that X and Y
      are independent. Second, the Fraser-Swinney algorithm is marginally the more
      accurate of the two algorithms when large data sets are used. With smaller data
      sets, however, the Fraser-Swinney algorithm reports structures that disappear
      when more data are available. Third, the algorithm constructed here requires
      about 0.5% of the computation time required by the Fraser-Swinney algorithm.

PMID- 16089851
TI  - Domain wall dynamics in an optical Kerr cavity.
AB  - An anisotropic (dichroic) optical cavity containing a self-focusing Kerr medium
      is shown to display a bifurcation between static--Ising--and moving--Bloch-
      domain walls, the so-called nonequilibrium Ising-Bloch transition (NIB). Bloch
      walls can show regular or irregular temporal behavior, in particular, bursting
      and spiking. These phenomena are interpreted in terms of the spatiotemporal
      dynamics of the extended patterns connected by the wall, which display complex
      dynamical behavior as well. Domain wall interaction, including the formation of
      bound states is also addressed.

PMID- 16089852
TI  - Long-range correlations in quantum-chaotic spectra.
AB  - We discuss the long-range spectral correlations in random matrices. Their
      universality for one-band spectra and its breakdown for multiband spectra are
      investigated and characterized. The long-range properties are complementary to
      the usual short-range properties, and are important for conductance fluctuations
      in mesoscopic systems. However, unlike short-range properties, they are not
      ubiquitous in model quantum-chaotic systems. We formulate a system of multiply
      kicked quantum rotors, and show that it exhibits both long-range and short-range
      correlations.

PMID- 16089853
TI  - Excitation functions of coupling.
AB  - The responses of nonlinear dynamics of two classes to coupling are investigated.
      It is shown both analytically and numerically that coupling has an excitation
      ability in a network of the linearly coupled systems. That is, when an uncoupled
      system is degenerated to a stable steady state from a limit cycle but in the
      "marginal" state due to the system parameter, an appropriate coupling strength
      can excite the limit cycle such that the coupled systems exhibit synchronous
      oscillation; when the uncoupled system is in a stable limit cycle but close to a
      chaotic attractor, a certain coupling strength can induce the chaotic attractor
      such that the coupled systems reach chaotic synchronization. Such excitation
      functions of coupling are different from its traditional role where coupling
      mainly synchronizes the coupled systems with the original dynamics of the
      uncoupled system.

PMID- 16089854
TI  - Out-of-phase oscillatory Turing patterns in a bistable reaction-diffusion system.
AB  - A new type of out-of-phase oscillatory Turing pattern is found in simulations of
      a simple two-variable model of a bistable reaction-diffusion system consisting of
      an autocatalytic activator reacting with a substrate that is replenished by a
      flow. This class of models can describe pH oscillators or enzymatic reactions. No
      Hopf instability is necessary for this type of oscillatory Turing pattern.

PMID- 16089855
TI  - Relation between observability and differential embeddings for nonlinear
      dynamics.
AB  - In the analysis of a scalar time series, which lies on an m-dimensional object, a
      great number of techniques will start by embedding such a time series in a d
      dimensional space, with d>m. Therefore there is a coordinate transformation
      phi(s) from the original phase space to the embedded one. The embedding space
      depends on the observable s(t). In theory, the main results reached are valid
      regardless of s(t). In a number of practical situations, however, the choice of
      the observable does influence our ability to extract dynamical information from
      the embedded attractor. This may arise in problems in nonlinear dynamics such as
      model building, control and synchronization. To some degree, ease of success will
      depend on the choice of the observable simply because it is related to the
      observability of the dynamics. In this paper the observability matrix for
      nonlinear systems, which uses Lie derivatives, is revisited. It is shown that
      such a matrix can be interpreted as the Jacobian matrix of phi(s)--the map
      between the original phase space and the differential embedding induced by the
      observable--thus establishing a link between observability and embedding theory.

PMID- 16089856
TI  - Complex-ordered patterns in shaken convection.
AB  - We report and analyze complex patterns observed in a combination of two standard
      pattern forming experiments. These exotic states are composed of two distinct
      spatial scales, each displaying a different temporal dependence. The system is a
      fluid layer experiencing forcing from both a vertical temperature difference and
      vertical time-periodic oscillations. Depending on the parameters these forcing
      mechanisms produce fluid motion with either a harmonic or a subharmonic temporal
      response. Over a parameter range where these mechanisms have comparable influence
      the spatial scales associated with both responses are found to coexist, resulting
      in complex, yet highly ordered patterns. Phase diagrams of this region are
      reported and criteria to define the patterns as quasiperiodic crystals or
      superlattices are presented. These complex patterns are found to satisfy four
      mode (resonant tetrad) conditions. The qualitative difference between the present
      formation mechanism and the resonant triads ubiquitously used to explain complex
      ordered patterns in other nonequilibrium systems is discussed. The only exception
      to quantitative agreement between our analysis based on Boussinesq equations and
      laboratory investigations is found to be the result of breaking spatial symmetry
      in a small parameter region near onset.

PMID- 16089857
TI  - Quantum computation and analysis of Wigner and Husimi functions: toward a quantum
      image treatment.
AB  - We study the efficiency of quantum algorithms which aim at obtaining phase-space
      distribution functions of quantum systems. Wigner and Husimi functions are
      considered. Different quantum algorithms are envisioned to build these functions,
      and compared with the classical computation. Different procedures to extract more
      efficiently information from the final wave function of these algorithms are
      studied, including coarse-grained measurements, amplitude amplification, and
      measure of wavelet-transformed wave function. The algorithms are analyzed and
      numerically tested on a complex quantum system showing different behavior
      depending on parameters: namely, the kicked rotator. The results for the Wigner
      function show in particular that the use of the quantum wavelet transform gives a
      polynomial gain over classical computation. For the Husimi distribution, the gain
      is much larger than for the Wigner function and is larger with the help of
      amplitude amplification and wavelet transforms. We discuss the generalization of
      these results to the simulation of other quantum systems. We also apply the same
      set of techniques to the analysis of real images. The results show that the use
      of the quantum wavelet transform allows one to lower dramatically the number of
      measurements needed, but at the cost of a large loss of information.

PMID- 16089858
TI  - Long-lived transient behavior in an n+-n-n+ semiconductor device with optical
      stochasticity.
AB  - We numerically study the response time of an ultrafast microwave switch, i.e., a
      GaAs-based Gunn device, under stochastic stimuli. The conducting states in this
      semiconductor device can be controlled in the presence of laser illumination near
      the doping notch. With the consideration of the additional randomness in laser
      intensity, the switching time from the initial unstable state to the final stable
      state will increase. Therefore, the so-called noise delayed decay of unstable
      states in an n+-n-n+ semiconductor device is demonstrated.

PMID- 16089859
TI  - Turing instability controlled by spatiotemporal imposed dynamics.
AB  - The study of the spatiotemporal response of pattern forming systems to spatially
      resonant external forcing has unveiled striking new phenomena which challenge the
      understanding of self-organization in nonlinear, nonequilibrium systems. Here we
      show that a simple spatiotemporal two-dimensional forcing of a system supporting
      an intrinsic wavelength but no intrinsic frequency, under conditions of spatial
      resonance, may induce complex and entirely new spatiotemporal behaviors which do
      not reflect in any simple way the structure of the imposed forcing. We
      demonstrate this phenomenon in the Turing regime of the (photosensitive) CDIMA
      reaction by projecting a traveling stripe light pattern onto the reactor. By
      controlling the velocity of the forcing we induce distinct dynamical regimes that
      express the externally imposed frequency in new and intriguing ways. A detailed
      analysis of the experimental relevant parameters is presented.

PMID- 16089860
TI  - Formation of Fabry-Perot resonances in double-barrier chaotic billiards.
AB  - We study wave transport through a chaotic quantum billiard attached to two
      waveguides via barriers of arbitrary transparencies in the semiclassical limit of
      a large number of open scattering channels. We focus attention on the ergodic
      regime, which is described by using a random-matrix approach to chaotic resonance
      scattering together with an extended version of Nazarov's circuit theory. By
      varying the relative strength of the barriers' transparencies a reorganization of
      the relevant resonances in the energy interval where transport takes place leads
      to a full suppression of high transmission modes. We provide a detailed
      quantitative description of the process by means of both numerical and analytical
      evaluations of the average density of transmission eigenvalues. We show that the
      density of Fabry-Perot modes can be used as a kind of order parameter for this
      quantum transition. A diagram is presented as a function of the transparencies of
      the barriers exhibiting the transport regimes and the transition lines.

PMID- 16089861
TI  - Exponential decay of chaotically advected passive scalars in the zero diffusivity
      limit.
AB  - The time asymptotic decay of the variance of a passive scalar in a chaotic flow
      is studied. Two mechanisms for this decay, which involve processes at short and
      long length scales, respectively, are considered. The validity of the short
      length scale mechanism, which is based on Lagrangian stretching theory, is
      discussed. We also investigate the regimes of applicability and observable
      signatures of the two mechanisms. Supporting evidence is provided by high
      resolution numerical experiments.

PMID- 16089862
TI  - Surface tension effects on the behavior of two cavities near a rigid wall.
AB  - Surface tension effects on the behavior of two initially spherical cavities
      growing and collapsing axisymmetrically above and near a rigid wall are
      investigated numerically by boundary integral method. The numerical simulations
      are performed for different dimensionless maximal cavity sizes, different
      dimensionless distances between the two cavities and those between the wall and
      the two cavities, and different values of Weber number. It is found that surface
      tension effects will resist the deformation of a cavity and make it closer to
      spherical during its growth phase, and make it collapse faster. For the case
      where the lower cavity is much smaller than the upper one, when the Weber number
      is less than or equal to 20, during the collapse phase, surface tension will have
      substantial effects on the behavior of the lower cavity such as change the form
      or the direction of its liquid jet if the Bjerknes forces to the lower cavity
      induced by the wall and the upper one are nearly equal. In all of the other
      cases, when the Weber number is greater than or equal to 10, surface tension will
      not have qualitative effects on the behavior of the cavity but change the length,
      width or sizes of its liquid jet. It is also found that for a convex cavity,
      surface tension has the effects on cavity behavior similar to those of the
      difference between the ambient pressure and the saturated vapor pressure inside
      the cavities. The above phenomena induced by surface tension effects are
      explained by this mechanism.

PMID- 16089863
TI  - Unsteady free-surface waves due to a submerged body moving in a viscous fluid.
AB  - Unsteady viscous free-surface waves generated by a three-dimensional submerged
      body moving in an incompressible fluid of infinite depth are investigated
      analytically. It is assumed that the body experiences a Heaviside step change in
      velocity at the initial instant. Two categories of the velocity change, (i) from
      zero to a constant and (ii) from a constant to zero, will be analyzed. The flow
      is assumed to be laminar and the submerged body is mathematically represented by
      an Oseenlet. The Green functions for the unbounded unsteady Oseen flows are
      derived. The solutions in closed integral form for the wave profiles are given.
      By employing Lighthill's two-stage scheme, the asymptotic representations of free
      surface waves in the far wake for large Reynolds numbers are derived. It is shown
      that the effects of viscosity and submergence depth on the free-surface wave
      profiles are respectively expressed by the exponential decay factors.
      Furthermore, the unsteady wave system due to the suddenly starting body consists
      of two families of steady-state waves and two families of nonstationary waves,
      which are confined within a finite region. As time increases, the waves move away
      from the body and the finite region extends to an infinite V-shaped region. It is
      found that the nonstationary waves are the transient response to the suddenly
      started motion of the body. The waves due to a suddenly stopping body consist of
      a transient component only, which vanish as time approaches infinity.

PMID- 16089864
TI  - Fast-convergent iterative scheme for filtering velocity signals and finding
      Kolmogorov scales.
AB  - The present fundamental knowledge of fluid turbulence has been established
      primarily from hot- and cold-wire measurements. Unfortunately, however, these
      measurements necessarily suffer from contamination by noise since no certain
      method has previously been available to optimally filter noise from the measured
      signals. This limitation has impeded our progress of understanding turbulence
      profoundly. We address this limitation by presenting a simple, fast-convergent
      iterative scheme to digitally filter signals optimally and find Kolmogorov scales
      definitely. The great efficacy of the scheme is demonstrated by its application
      to the instantaneous velocity measured in a turbulent jet.

PMID- 16089865
TI  - Three-dimensional thermal convection of viscoelastic fluids.
AB  - The influence of inertia and elasticity on the onset and stability of three
      dimensional thermal convection is examined for highly elastic polymeric solutions
      with constant viscosity. These solutions are known as Boger fluids, and their
      rheology is approximated by the Oldroyd-B constitutive equation. The onset and
      the stability of steady convective patterns, namely rolls, hexagons and squares,
      are studied in the post-critical range of the Rayleigh number by using an
      amplitude equation approach. The square pattern is found to be unstable. In
      contrast to Newtonian fluids, the hexagonal pattern can be stable for a certain
      range of elasticity.

PMID- 16089866
TI  - Stability of a viscoelastic falling film with surfactant subjected to an
      interfacial shear.
AB  - The long-wavelength stability is analyzed for a surfactant-laden, viscoelastic
      liquid flowing down an inclined plane when the liquid undergoes additional
      interfacial shear. The upper convected Maxwell model is employed for describing
      the elastic nature of the fluid. The system stability is characterized by the
      interface and the surfactant modes. The interface mode involves both elastic and
      Marangoni effects that modulate the stability with applied shears and gravity
      driven flow. The surfactant mode is only determined by the shear-induced
      Marangoni effects. A phase diagram is established to identify the dominant mode
      and the overall features of instability. It reveals that the system is
      susceptible to instability, except in a stable window when the applied shear
      opposes the gravity-driven flow.

PMID- 16089867
TI  - Scaling of longitudinal and transverse velocity increments in a cylinder wake.
AB  - Longitudinal and transverse velocity increments are measured both temporally and
      spatially using two X-wire probes in the intermediate region of a cylinder wake
      over Taylor microscale Reynolds numbers in the range of 100-300. The scaling
      exponents of both the spatial and temporal longitudinal velocity increments agree
      favorably with the predictions of Kolmogorov and She and Leveque. The scaling
      exponents of the transverse velocity increments are considerably smaller than
      those of the longitudinal ones, with the values for spatial transverse velocity
      increments being slightly larger than the temporal ones. The difference between
      the scaling exponents of the longitudinal and transverse velocity increments is
      examined against the refined similarity hypotheses for transverse velocity
      increments (RSHT) proposed by Chen It is found that the RSHT can account for the
      difference between the scaling exponents of the longitudinal and spatial
      transverse velocity increments at all Reynolds numbers considered.

PMID- 16089868
TI  - Natural convection in tilted cylindrical cavities embedded in rocks.
AB  - This paper presents a theoretical investigation of the low Rayleigh number
      conjugate natural convection in a slender tilted cylindrical cavity which is
      embedded in a solid that is subject to a uniform vertical temperature gradient.
      Two cases have been analyzed; a fluid-filled cavity and a cavity filled with a
      fluid-saturated porous medium. The temperature of the solid and the velocity,
      temperature, and pressure in the cavity have been determined by analytically
      solving the coupled problems within and around the cavity. The effect of the
      ratio of the thermal conductivity of the material in the cavity to the thermal
      conductivity of the solid on the structure of the convection flow is discussed.
      The theoretical results for convection in the fluid-filled cavity are shown to be
      in good agreement with experimental PIV measurements.

PMID- 16089869
TI  - Elongation and burst of axisymmetric viscoelastic droplets: a numerical study.
AB  - The dynamics of elongation and burst of an isolated viscoelastic drop are
      investigated numerically in the special case of a viscosity ratio lambda = 1 . We
      show that the burst threshold is not affected by viscoelasticity itself, whereas
      the stationary drop morphology is. A dimple at the tips of the drop can even be
      observed when elastic effects are large. The burst dynamics is very sensitive to
      the presence of viscoelasticity: at low elasticity burst is slowed down while for
      large elasticity levels it becomes even faster than the Newtonian situation.

PMID- 16089870
TI  - Two typical time scales of the piston effect.
AB  - The existence of a fourth mode of heat transfer near the critical point, named
      the piston effect, has been known for more than a decade. The typical time scale
      of temperature relaxation due to this effect was first predicted by Onuki [Phys.
      Rev A 41, 2256 (1990)], and this author's formula has been extensively used since
      then to predict the thermal behavior of near-critical fluids. Recent studies,
      however, pointed out that the critical divergence of the bulk viscosity could
      have a strong influence on piston-effect-related processes. In this paper, we
      conduct a theoretical analysis of near-critical temperature relaxation showing
      that the piston effect is not governed by one (as was until now believed) but by
      two typical time scales. These two time scales exhibit antagonistic asymptotic
      behaviors as the critical point is approached: while the classical piston-effect
      time scale (as predicted by Onuki ) goes to zero at the critical point (critical
      speeding up), the second time scale (related to bulk viscosity) goes to infinity
      (critical slowing down). Based on this property, an alternative method for
      measuring near-critical bulk viscosity is proposed.

PMID- 16089871
TI  - Convective instability of magnetic fluids under alternating magnetic fields.
AB  - A theoretical investigation of the convective instability problem in the thin
      horizontal layer of a magnetic fluid heated from below and under alternating
      magnetic fields is carried out. Both the quasistationary model and the model with
      internal rotation with vortex viscosity are considered. Floquet theory is used
      for discussing the existence and stability boundaries of the differential
      equations with periodic coefficients. The Chebyshev pseudospectral method is
      employed to discretize the partial differential equation, and QZ algorithm is
      used for solving the eigenvalue problem. For quasistationary model, both free
      free and rigid-rigid boundary cases are considered, whereas for the model with
      internal rotation only rigid-rigid boundary condition is studied. The effect of
      frequency variations on the stability are considered in all the cases.

PMID- 16089872
TI  - Anomalous scaling of passively advected magnetic field in the presence of strong
      anisotropy.
AB  - Inertial-range scaling behavior of high-order (up to order N=51 ) two-point
      correlation functions of a passively advected vector field has been analyzed in
      the framework of the rapid-change model with strong small-scale anisotropy with
      the aid of the renormalization group and the operator-product expansion.
      Exponents of the power-like asymptotic behavior of the correlation functions have
      been calculated in the one-loop approximation. These exponents are shown to
      depend on anisotropy parameters in such a way that a specific hierarchy related
      to the degree of anisotropy is observed. Deviations from power-law behavior like
      oscillations or logarithmic behavior in the corrections to correlation functions
      have not been found.

PMID- 16089873
TI  - Intermittency in two-dimensional turbulence with drag.
AB  - We consider the enstrophy cascade in forced two-dimensional turbulence with a
      linear drag force. In the presence of linear drag, the energy wave-number
      spectrum drops with a power law faster than in the case without drag, and the
      vorticity field becomes intermittent, as shown by the anomalous scaling of the
      vorticity structure functions. Using previous theory, we compare numerical
      simulation results with predictions for the power law exponent of the energy wave
      number spectrum and the scaling exponents of the vorticity structure functions
      zeta(2q). We also study, both by numerical experiment and theoretical analysis,
      the multifractal structure of the viscous enstrophy dissipation in terms of its
      Renyi dimension spectrum D(q). We derive a relation between D(q) and zeta(2q),
      and discuss its relevance to a version of the refined similarity hypothesis. In
      addition, we obtain and compare theoretically and numerically derived results for
      the dependence on separation r of the probability distribution of delta(r)omega,
      the difference between the vorticity at two points separated by a distance r. Our
      numerical simulations are done on a 4096 x 4096 grid.

PMID- 16089874
TI  - Quasi-isentropic compression by ablative laser loading: response of materials to
      dynamic loading on nanosecond time scales.
AB  - The TRIDENT laser was used to induce quasi-isentropic compression waves to
      approximately 15 GPa in samples of Si, by ablative loading using a laser pulse
      whose intensity increased smoothly over 2.5 ns. The intensity history of the
      pulse and the velocity history at the opposite surface of the sample were
      recorded. Experiments were performed using samples of two different thicknesses
      simultaneously, in which the evolution of the compression wave was clearly
      visible. Isentropic stress states deduced were consistent with the previously
      investigated response of Si to uniaxial loading. The ablative loading was
      simulated using radiation hydrodynamics, with different equations of state in the
      plasma and condensed regions and including elasticity in the solid Si. These
      calculations reproduced the measured velocity histories quite well, demonstrating
      that quasi-isentropic compression was induced with no preheat from the laser
      drive. Normal continuum behavior was demonstrated to hold below nanosecond time
      scales for isentropic compression waves, with no evidence for nonequilibrium
      effects in the crystal lattice. Details of the velocity history over about 10 GPa
      were reproduced less well, suggesting a deficiency in the model used for
      compressed Si, which may be consistent with recent theoretical predictions of
      uniaxial compression at high strain rates.

PMID- 16089875
TI  - Oscillations in dc driven barrier discharges: numerical solutions, stability
      analysis, and phase diagram.
AB  - A short gas-discharge layer sandwiched with a semiconductor layer between planar
      electrodes shows a variety of spatiotemporal patterns. We focus on the
      spontaneous temporal oscillations that occur while a dc voltage is applied and
      while the system stays spatially homogeneous; the results for these oscillations
      apply equally to a planar discharge in series with any resistor with capacitance.
      We define the minimal model, identify its independent dimensionless parameters,
      and then present the results of the full time-dependent numerical solutions of
      the model as well as of a linear stability analysis of the stationary state. Full
      numerical solutions and the results of the stability analysis agree very well.
      The stability analysis is then used for calculating bifurcation diagrams. We find
      semiquantitative agreement with experiment for the diagram of bifurcations from
      stationary to oscillating solutions as well as for amplitude and frequency of the
      developing limit cycle oscillations.

PMID- 16089876
TI  - Stark broadening of hydrogen lines in dense plasmas: analysis of recent
      experiments.
AB  - In recent years experiments conducted by a number of different groups on line
      broadening of hydrogen lines, mainly H(alpha) on dense plasmas of densities
      larger than or equal to 10(18) e/cm3 have claimed significant differences from
      the predictions of the standard theory. At these high densities the standard
      theory predictions depend on some cutoffs, necessary to preserve unitarity, the
      long range approximation and to ensure the validity of a semiclassical picture.
      Furthermore, a new, supposedly "advanced" theory based on a number of incorrect
      assumptions and/or approximations with extra exotic effects has claimed good
      agreement with these experiments. In this work we produce benchmark simulation
      calculations for these data to identify relevant and not relevant physics for the
      parameters of these experiments. In this way, we evaluate claims of electron-ion
      coupling, ion dynamics, electron vs ion broadening, nonimpact effects, and
      nonperturbative effects. At least one data set is seen to be dubious, in
      agreement with previous analyses.

PMID- 16089877
TI  - Ionization fronts in planar dc discharge systems with high-ohmic electrode.
AB  - Electric breakdown and ionization fronts are considered theoretically in a
      sandwich-like dc discharge system consisting of two plane-parallel electrodes and
      a gaseous gap in between. The key system feature is a high-ohmic cathode opposite
      to an ordinary metal anode. Such systems have received much attention from
      experimental studies because they naturally support current patterns. Using
      adiabatic description of electrons and two-scale expansion we demonstrate that in
      the low-current Townsend mode the discharge is governed by a two-component
      reaction-diffusion system. The latter provides quantitative system description on
      the macroscopic time scale (i.e., much larger than the ion travel time). The
      breakdown appears as an instability of the uniform overvoltage state. A seed
      current fluctuation triggers a shock-like ionization front that propagates along
      the discharge plane with constant speed (typically approximately 10(4) cm/s).
      Depending on the cathode resistivity the front exhibits either monotonic or
      oscillatory behavior in space. Other breakdown features, such as damping
      transient oscillations of the global current, can also be found as solutions of
      the reaction-diffusion equations.

PMID- 16089878
TI  - Role of the thermophoretic force on the transport of nanoparticles in dusty
      silane plasmas.
AB  - A comparison, based on numerical modeling, is made between the different forces
      experienced by nanoparticles present in a low pressure capacitively coupled
      parallel-plate silane (Si H4 ) discharge. We investigate in particular the
      influence of the thermophoretic force on the spatial distribution of the
      nanoparticle density profiles, due to a thermal gradient in gas temperature
      induced by heating or cooling of the electrodes. A series of simulations with a
      one-dimensional fluid model are performed with asymmetrical variation of the
      electrode temperatures. It appears that the resulting density profile of the
      nanoparticles experiences a significant shift towards the cooler electrode as
      soon as a temperature difference is applied. Thus thermophoresis is capable of
      influencing the force balance of suspended nanoparticles in the plasma, even at
      relatively small electrode temperature differences.

PMID- 16089879
TI  - Anisotropy of the electron component in a cylindrical magnetron discharge. I.
      Theory of the multiterm analysis.
AB  - A general multiterm representation of the phase space electron distribution
      function in terms of spherical tensors is used to solve the Boltzmann kinetic
      equation in crossed electric and magnetic fields. The problem is formulated for
      an axisymmetric cylindrical magnetron discharge with the homogeneous magnetic
      field being directed axially and the electric field between the coaxial cathode
      and anode varying in radius only. A spherical harmonic representation of the
      velocity distribution function in Cartesian coordinates becomes especially
      cumbersome in the presence of the magnetic field. In contrast, the employment of
      a spherical tensor representation leads to a compact hierarchy of equations that
      accurately take into account the spatial inhomogeneities and anisotropy of the
      plasma in crossed fields. To describe the spatially inhomogeneous plasma the
      hierarchy of the kinetic equations is formulated in terms of the total energy and
      the radial coordinate. Appropriate boundary conditions at the electrodes for the
      tensor expansion coefficients are obtained.

PMID- 16089880
TI  - Anisotropy of the electron component in a cylindrical magnetron discharge. II.
      Application to real magnetron discharge.
AB  - The physical processes occurring in electrode regions and the positive column of
      a cylindrical magnetron discharge in crossed electric and magnetic fields are
      investigated based on the solution of the Boltzmann kinetic equation by a
      multiterm decomposition of the electron phase space distribution function in
      terms of spherical tensors. The influence of the distribution function anisotropy
      on the absolute values and radial profiles of the electron density and rates of
      various transport and collision processes is analyzed. The spiral lines for the
      directed particle and energy transport are obtained to illustrate the anisotropy
      effects in dependence on the magnetic field. The electron equipressure surfaces
      are constructed in the form of ellipsoids of pressure and their transformation in
      the cathode and anode regions is studied. A strong anisotropy of the energy flux
      tensor in contrast to a weak anisotropy of the momentum flux density tensor is
      found. Particular results are obtained for the cylindrical magnetron discharge in
      argon at pressure 3 Pa, current 200 mA, and magnetic fields ranging within 100
      and 400 G.

PMID- 16089881
TI  - Molecular dynamics simulations of optical conductivity of dense plasmas.
AB  - The optical conductivity sigma (omega) for dense Coulomb systems is investigated
      using molecular dynamics simulations on the basis of pseudopotentials to mimic
      quantum effects. Starting from linear response theory, the response in the long
      wavelength limit k=0 can be expressed by different types of autocorrelation
      functions (ACF's) such as the current ACF, the force ACF, or the charge density
      ACF. Consistent simulation data for transverse as well as longitudinal ACF's are
      shown which are based on calculations with high numerical accuracy. Results are
      compared with perturbation expansions which are restricted to small values of the
      plasma parameter. The relevance with respect to a quantum Coulomb plasma is
      discussed. Finally, results are presented showing a consistent description of
      these model plasmas in comparison to quantum statistical approaches and to
      experimental data.

PMID- 16089882
TI  - Charge-charge coupling effects on dipole emitter relaxation within a classical
      electron-ion plasma description.
AB  - Studies of charge-charge (ion-ion, ion-electron, and electron-electron) coupling
      properties for ion impurities in an electron gas are carried out on the basis of
      a regularized electron-ion potential without short-range Coulomb divergence. This
      work is motivated, in part, by questions arising from recent spectroscopic
      measurements revealing discrepancies with present-day theoretical descriptions.
      Many of the current radiative property models for plasmas include only single
      electron-emitter collisions and neglect some or all charge-charge interactions. A
      molecular-dynamics simulation of dipole relaxation is proposed here to allow
      proper account of many electron-emitter interactions and all charge-charge
      couplings. As illustrations, molecular-dynamics simulations are reported for the
      cases of a single ion embedded in an electron plasma and for a two-component ion
      electron plasma. Charge-charge coupling effects are discussed for hydrogen-like
      Balmer alpha lines at weak coupling conditions.

PMID- 16089883
TI  - Investigation of laser-irradiated Ar cluster dynamics from K-shell x-ray emission
      measurements.
AB  - Intense (up to a few 10(17) W/ cm2) femtosecond (down to 40 fs) laser pulses are
      focused onto a partially clusterized argon gas jet. The target was previously
      characterized and optimized in order to get a homogeneous and dense jet of
      clusters with a well controlled size. The interaction leads to x-ray emission
      that is absolutely calibrated and spectrally resolved using a high resolution
      time-integrated spectrometer in the K-shell range (from 2.9 to 4.3 keV). X-ray
      spectra are investigated as a function of different laser temporal parameters
      such as the nanosecond prepulse contrast, the laser pulse duration, and the
      femtosecond delay between two different laser pulses. The cluster size ranges
      from 180 to 350 angstroms and irradiation by laser pulses with both linear and
      circular polarization is investigated. The experimental results are discussed in
      terms of the laser-cluster interaction dynamics. They are compared with the
      predictions of collision-dominated nanoplasma models. However, further
      interaction processes are required in order to explain the observed
      characteristic lines demonstrating highly charged ions up to Ar16+.

PMID- 16089884
TI  - Residual energy in optical-field-ionized plasmas with the longitudinal motion of
      electrons included.
AB  - The space-charge effect on the residual energy of electrons in optical-field
      ionized plasmas is studied in detail by an extended simplified model and the
      cloud-in-cell simulation, with the longitudinal motion of electrons included. It
      is found that in moderate conditions the space-charge field can influence the
      residual energy of electrons effectively by matching the space-charge field with
      laser pulse. The effect of stimulated Raman scattering on electron temperature is
      also investigated in detail. Finally, a comparison is made between the results
      and experimental data.

PMID- 16089885
TI  - Statistical approach to beam shaping.
AB  - A method for beam shaping based on fitting the power moments of the final beam
      intensity distribution and independent of the optical system particularities is
      suggested. It is shown how one can analytically calculate any moment of the final
      phase space distribution using the moments of the initial distribution and the
      optical system transfer map. Numerical tests carried out for a final focus system
      have demonstrated the usefulness of the approach developed here.

PMID- 16089886
TI  - Effects of delayed Kerr nonlinearity and ionization on the filamentary ultrashort
      laser pulses in air.
AB  - We present a systematic study of filamentary ultrashort laser pulses in air,
      through numerical solutions of the nonlinear Schrodinger equation for various
      contributions of the delayed Kerr nonlinearity. The results show that a
      relatively larger contribution of the delayed Kerr nonlinearity will lead to a
      longer stable filament. This is explained from the transfer of the nonlinear
      contributions from the frontier part to the back of the pulse and the
      counterbalanced action of the negative plasma induced nonlinearity by the delayed
      Kerr nonlinearity in the trailing part of the pulses. Furthermore, effect of
      ionization on the stability of the filament is investigated. Two formulas are
      used to generate the data of the ionization, i.e., the Perelemov, Popov, and
      Terent'ev (PPT) and the Ammosov, Delone, and Krainov formula. It is found that
      simulation with higher ionization rate (PPT) could generate a more stable and
      longer filament.

PMID- 16089887
TI  - Approach for simultaneous measurement of two-dimensional angular distribution of
      charged particles: spherical aberration correction using an ellipsoidal mesh.
AB  - An approach for simultaneous measurement of two-dimensional angular distribution
      of charged particles is proposed. This concerns spherical aberration correction
      in electrostatic lenses with potential use of a mesh. In an earlier work, an
      effective use of a spherical mesh has succeeded to obtain a large acceptance
      angle limited to around 60 degrees (+/- 30 degrees). The present work is aimed at
      dramatically increasing acceptance angles limited in conventional lenses. For
      this purpose, spherical aberration behavior of mesh lenses is studied in detail
      using an analytical approximation and ray tracing, with particular attention paid
      to the effect of the mesh shape. It is shown here that the lens ability to
      correct spherical aberration over wide aperture angles can be effectively
      enhanced by the ellipsoidal deformation of a spherical mesh. We demonstrate that
      an effective use of an ellipsoidal mesh provides remarkable performance
      characteristics for electrostatic lenses, which opens new possibilities in
      surface and materials analysis techniques. Simple examples of ellipsoidal mesh
      lenses are presented that allow very wide acceptance angles of up to 120 degrees.

PMID- 16089888
TI  - Dynamics and stabilization of the Elettra storage-ring free-electron laser.
AB  - The ultimate performance of a storage-ring free-electron laser in terms of light
      stability and extracted power depends on the possibility of simultaneously
      controlling the electron-beam and laser dynamics. As a preliminary requirement,
      the level of longitudinal and transverse electron-beam stability must be high
      enough to guarantee the laser start-up and growth. This is usually obtained by
      means of dedicated feedback systems. Once such a requirement is satisfied, the
      possibility of establishing and maintaining a continuous-wave operation mode
      finally resides in a deep understanding of the strongly coupled laser-electrons
      dynamics. For this purpose, we have developed a simple theoretical model which
      has been proved to be able to provide insight into the evolution of the laser
      intensity. In this framework, we have also proposed the possibility of utilizing
      a derivative closed-loop feedback to create or enlarge the region of stable
      signal. A feedback of this type has been implemented on the Elettra storage-ring
      free-electron laser. The obtained results, which fully confirm our predictions,
      are discussed in this paper.

PMID- 16089889
TI  - Trapping Bragg solitons by a pair of defects.
AB  - We study collisions of moving solitons in a fiber Bragg grating with a structure
      composed of two local defects of the grating, attractive or repulsive. Results
      are summarized in the form of diagrams showing the share of the trapped energy as
      a function of the soliton's velocity and defects' strength. The moving soliton
      can be trapped by a cavity bounded by repulsive defects; a well-defined region of
      the most efficient trapping is identified. The trapped soliton performs
      persistent oscillations in the cavity, with the frequency in the GHz range. For
      attractive defects, essential differences are found from the earlier studied case
      of the collision of a soliton with a single defect: in this case, too, there
      appears a well-defined region of the most efficient trapping, and the largest
      velocity, up to which the soliton can be captured, increases. The findings may be
      significant for experiments aimed at the creation of "standing-light" pulses in
      the fiber gratings and for related applications. Collisions between identical
      solitons moving across the two-defect structure are also studied. On the
      attractive set, soliton-soliton collisions may give rise to symmetric capture of
      the solitons by both defects or merger into a single pulse trapped at one defect.

PMID- 16089890
TI  - Macroscopic diagnostics of microscopic friction phenomena.
AB  - We show that the static friction force which must be overcome to render a
      sticking contact sliding is reduced if an external torque is also exerted. As a
      test system we study a planar disk lying on a horizontal flat surface. We perform
      experiments and compare with analytical results to find that the coupling between
      static friction force and torque is nontrivial: It is not determined by the
      Coulomb friction laws alone, instead it depends on the microscopic details of
      friction. Hence, we conclude that the macroscopic experiment presented here
      reveals details about the microscopic processes lying behind friction.

PMID- 16089891
TI  - Steady light transport under flow: characterization of evolving dense random
      media.
AB  - We describe in this letter a new rheo-optical apparatus able to measure the
      photon transport length l* in an evolving random medium. First, the appropriate
      solution of the diffusion equation for oil in water, stable, micron-sized
      emulsions is compared successfully with the measured spatial distribution of
      incoherent backscattered light given by the new apparatus. Further validation is
      provided using stable samples of varying sizes and volume fractions (1% to 64%)
      and comparing measurements with Mie-Percus-Yevick calculations based on
      independent small-angle light scattering (SALS) measurements. As a typical
      example application of the system, the emulsification of a different oil in water
      system is studied in situ and dynamically. The continuous temporal measurements
      show the decrease of the average size versus time, in excellent quantitative
      agreement with independent SALS measurements. This evidences that this system is
      able to probe continuously and nonintrusively the microscopic and macroscopic
      flow-induced organization of suspensions.

PMID- 16089892
TI  - Design of omnidirectional and multiple channeled filters using one-dimensional
      photonic crystals containing a defect layer with a negative refractive index.
AB  - The band structures of one-dimensional photonic crystals containing a defect
      layer with a negative refractive index are studied, showing that the defect modes
      possess three types of dispersion: positive, zero, and negative types. Based on
      these three types of dispersion, practical designs for large incident angle
      filters without polarization effect and for narrow frequency and sharp angular
      filters are suggested. Moreover, the splitting of one degenerate defect mode into
      multiple defect modes is observed in the band gap when the parameters of the
      defect layer vary. This mode splitting phenomenon can be used to design multiple
      channeled filters or filters with a rectangular profile. The dispersion
      multiplicity of the defect modes can be understood by an approximate formula, and
      the critical condition for the defect mode splitting is also analyzed. Based on
      these analyses, practical optimization design of omnidirectional filter is also
      suggested.

PMID- 16089893
TI  - Left-handed and right-handed metamaterials composed of split ring resonators and
      strip wires.
AB  - The behavior of two structures composed of split ring resonators (SRRs) and strip
      wires (SWs) is examined through full wave simulations. It is shown that both
      structures exhibit a transmission peak in the region where the real parts of the
      electric permittivity and magnetic permeability are presumed to be negative, a
      property which is usually assumed to imply a negative index of refraction.
      However, an analysis of the dispersion characteristics and insertion phase of the
      two structures shows that the first structure, in which the SRRs and SWs are
      printed on opposite sides of a dielectric substrate, is a left-handed medium in
      the passband, whereas the second structure, in which SRRs and SWs are printed on
      the same side, is a right-handed medium in the passband. Hence the transmission
      magnitude alone does not provide sufficient evidence of a negative index of
      refraction. To determine the sign of the index correctly, the insertion phase for
      propagation through several lengths of the structure or calculations of
      dispersion diagrams are necessary. The impact of the unit cell size on the
      "handedness" of the structure is also examined.

PMID- 16089894
TI  - Coherent control of stimulated emission inside one-dimensional photonic crystals.
AB  - In this paper, the quasinormal mode (QNM) theory is applied to discuss the
      quantum problem of an atom embedded inside a one-dimensional (1D) photonic band
      gap (PBG) cavity pumped by two counterpropagating laser beams. The e.m. field is
      quantized in terms of the QNMs in the 1D PBG and the atom modeled as a two-level
      system is assumed to be weakly coupled to just one of the QNMs. The main result
      of the paper is that the decay time depends on the position of the dipole inside
      the cavity, and can be controlled by the phase difference of the two laser beams.

PMID- 16089895
TI  - Hybridization theory between localized mode and free propagating modes for light
      scattering from a dielectric sphere.
AB  - Light scattering from a homogeneous dielectric sphere is discussed in terms of
      hybridization between a localized mode excited inside the dielectric sphere and
      free propagating modes in vacuum. This theory is a photonic counterpart of the
      Anderson model in electron systems, yielding a rigorous theoretical foundation of
      the heavy photon concept, which was numerically proposed for almost flat photonic
      bands. The magnitude of the hybridization is analytically expressed. The
      localized mode is identified with the photon virtual bound state. In order to
      confirm the validity of the present theory, a comparison is made between the
      present theory and conventional numerical calculation for results of the photonic
      density of states.

PMID- 16089896
TI  - Computation of the intensities of parametric holographic scattering patterns in
      photorefractive crystals.
AB  - The present work represents a first attempt to perform computations of output
      intensity distributions for different parametric holographic scattering patterns.
      Based on the model for parametric four-wave mixing processes in photorefractive
      crystals and taking into account realistic material properties, we present
      computed images of selected scattering patterns. We compare these calculated
      light distributions to the corresponding experimental observations. Our analysis
      is especially devoted to dark scattering patterns as they make high demands on
      the underlying model.

PMID- 16089897
TI  - Vibrations of Euler's disk.
AB  - A model of a partially deformable Euler disk is presented that allows transverse
      vibrations to be treated with the techniques of classical analytical mechanics.
      The model clearly shows that the increasing audible frequency produced during
      motion can be directly related to the forcing effect of the reaction and the
      angular velocity of the contact point. The material of the disk seems to play a
      role in affecting the intensity and quality of the sound, but not its pitch.
      Moreover, the friction force grows rapidly with the decline of the disk, thus
      causing the slipping that is partially responsible for the abrupt end of the
      motion. The model also supports the conjecture [P. Kessler and O. M. O'Reilly,
      Regul. Chaotic Dyn. 7, 49 (2002)] that the vibrations themselves contribute to
      this phenomenon by causing a loss of contact with the surface at small angles of
      inclination.

PMID- 16089898
TI  - Tunable sharp angular defect mode with invariant transmitted frequency range in
      one-dimensional photonic crystals containing negative index materials.
AB  - We propose a different photonic crystal structure with a novel defect mode. In
      this defect mode, the transmitted angle is sharp and the pass band is of
      rectangular shape. Surprisingly, there is a critical refractive index of the
      defect layer in the crystal. By changing the refractive index in a range higher
      than this critical value, the sharp transmitted angle can be tuned with
      transmitted frequency range maintained; when the refractive index is lower than
      this critical value, only the transmittance of the defect mode is adjusted, with
      the sharp transmitted angle and transmitted frequency kept unchanged. All these
      phenomena provide possible mechanisms for angular filtering, optical switching
      (i.e., an optical switch working in the angular domain) and setting optical
      limits.

PMID- 16089899
TI  - Existence and stability of accelerating solitons in sliding-frequency filter
      systems.
AB  - Sliding-frequency filter systems are known to admit two families of accelerating
      solitons: high-amplitude and low-amplitude families. Such equilibrium solutions
      are computed here, for a wide range of filter strengths, as self-similar
      solutions having Airy function asymptotics. In a limited parameter region, the
      profile possesses a secondary small hump. The high-amplitude solitons are found
      to be stable over a region of parameter space which is here determined by the
      Evans function method, adjusted to Airy function asymptotics. The loss of
      stability is due to a Hopf bifurcation.

PMID- 16089900
TI  - Beam shifting of an anisotropic negative refractive medium.
AB  - We rigorously derive the formulas of the total electric and magnetic fields in a
      slab of anisotropic negative refractive medium by use of Maxwell's equations. A
      beam shifting is exhibited from a Gaussian beam for an anisotropic negative
      refractive slab. Our results indicate that there exist two possible (positive or
      negative) beam shifting for an anisotropic negative refractive medium due to the
      special anisotropic properties, which is distinct from the case of an isotropic
      negative refractive slab. Physical insights are also presented.

PMID- 16089901
TI  - Generation of solitons by a boxlike pulse in the derivative nonlinear Schrodinger
      equation with nonvanishing boundary conditions.
AB  - The creation of solitons of the derivative nonlinear Schrodinger equation with
      nonvanishing boundary conditions from a boxlike initial pulse is considered. The
      inverse scattering transform is used. An equation for soliton eigenvalues is
      obtained. It is shown that simultaneous generation of breathers (solitons with
      internal oscillations) and one-parametric (nonoscillating) bright or dark
      solitons is possible. For some sets of initial parameters only breathers or only
      one-parametric solitons emerge. No more than three bright solitons can emerge
      (possibly, simultaneously with breathers) in any case, while dark solitons or
      breathers can arise in arbitrary number when the corresponding thresholds are
      exceeded. Analytical estimates for the number of generated solitons and the
      corresponding thresholds are given in some particular cases.

PMID- 16089902
TI  - Motion of discrete solitons assisted by nonlinearity management.
AB  - We demonstrate that time-periodic modulation of the nonlinearity coefficient in
      the discrete nonlinear Schrodinger equation strongly facilitates creation of
      traveling solitons in the lattice. We predict this possibility in a semi
      qualitative form analytically, and test it in direct numerical simulations.
      Systematic computations reveal several generic dynamical regimes, depending on
      the amplitude and frequency of the time modulation, and on the initial thrust
      which sets the soliton in motion. These regimes include irregular motion of the
      soliton, regular motion of a decaying one, and regular motion of a stable
      soliton. The motion may occur in both the straight and reverse directions,
      relative to the initial thrust. In the case of stable motion, extremely long
      simulations in a lattice with periodic boundary conditions demonstrate that the
      soliton keeps moving indefinitely long without any visible loss. Velocities of
      moving stable solitons are in good agreement with the analytical prediction,
      which is based on requiring a resonance between the ac drive and motion of the
      soliton through the periodic lattice. The generic dynamical regimes are mapped in
      the model's parameter space. Collisions between moving stable solitons are
      briefly investigated too, with a conclusion that two different outcomes are
      possible: elastic bounce, or bounce with mass transfer from one soliton to the
      other. The model can be realized experimentally in a Bose-Einstein condensate
      trapped in a deep optical lattice.

PMID- 16089903
TI  - Nonlinear frequency conversion with quasi-phase-mismatch effect.
AB  - In conventional frequency conversion based on chi(2)-induced nonlinear optical
      effects, a number of phase-matching techniques have been deployed to resolve the
      phase mismatch between the interacting waves. In this work, we report that in the
      quasi-phase-matching scheme, the accumulation of the phase mismatch can induce a
      quasi-phase-mismatch effect. And on the contrary, instead of eliminating the
      phase mismatch, modulating the quasi-phase-mismatch effect can lead to bandwidth
      enhancement and multiple-wavelength conversion. Both of these are essential
      factors for applications in nonlinear frequency conversion. As examples, designs
      with reset-periodic and cascaded-periodic optical superlattices based on such
      modulation are presented.

PMID- 16089904
TI  - Synthesis and analysis of linear and nonlinear acoustical vortices.
AB  - Acoustical screw dislocations are synthesized in various configurations with a
      versatile experimental setup. The experimental setup is based on the inverse
      filter technique and allows one to synthesize one or more acoustical vortices
      with a chosen width, position, and topological charge. An interesting feature of
      this experimental facility to study screw dislocation behavior is the direct
      measurement in amplitude and phase. This characteristic is used to develop an
      original method of decomposition of an acoustical vortex field in order to
      analyze the acoustical vortices. Moreover, the behaviors of two acoustical
      vortices of the same or opposite charge have been studied experimentally and
      compared to theoretical laws.

PMID- 16089905
TI  - Generalized geometric cluster algorithm for fluid simulation.
AB  - We present a detailed description of the generalized geometric cluster algorithm
      for the efficient simulation of continuum fluids. The connection with well-known
      cluster algorithms for lattice spin models is discussed, and an explicit full
      cluster decomposition is derived for a particle configuration in a fluid. We
      investigate a number of basic properties of the geometric cluster algorithm,
      including the dependence of the cluster-size distribution on density and
      temperature. Practical aspects of its implementation and possible extensions are
      discussed. The capabilities and efficiency of our approach are illustrated by
      means of two example studies.

PMID- 16089906
TI  - Molecular dynamics study of the influence of wall-gas interactions on heat flow
      in nanochannels.
AB  - Especially at the nanometer scale interfaces play an important role. The effect
      of the wettability on the solid-liquid interface has already been studied with
      molecular dynamics. In this paper we study the dependence of wetting on the solid
      gas interface for different density gases and investigate the influence of
      wetting on the heat transport properties over such an interface using molecular
      dynamics. Subsequently we show how the flow profile of a gas flowing along a
      surface also depends on this wettability. These simulations show that wettability
      increases the conductivity of a solid to a stationary gas and decreases the flow
      velocity near the interface for a gas flow. These two effects influence the
      cooling of a solid achieved by a cold gas flowing along its surface in opposite
      ways. However, we show that a higher wettability has a positive net effect on the
      cooling, explaining experimental results that showed an increased heat cooling
      effect of hydrophilic over hydrophobic microchannels.

PMID- 16089907
TI  - Numerical investigation of the spreading-receding cycle in a concentration
      dependent lattice gas automaton diffusion model.
AB  - This work forms the second part of a numerical study about the dynamics of
      diffusive fronts in concentration-dependent diffusion processes. We previously
      demonstrated that one-dimensional spreading of a density front in a concentration
      dependent microscopically heterogeneous, macroscopically homogeneous isotropic
      lattice gas automaton (LGA) substantially deviates from the t(1/2) relation
      expected from Fick's law over large periods of time. The time exponent was found
      to be larger than 1/2 , i.e., spreading of the density front is enhanced with
      respect to standard Fickian diffusion. In this note, we specifically investigate
      the dynamics of receding by using the same LGA model. We show here that the
      receding process essentially scales as t(1/2). The LGA simulations of diffusive
      fronts thus lead to the paradoxical result of Fick's-compatible receding and
      anomalous superdiffusive spreading for the same microscopic random structure and
      the same boundary conditions. The results also suggest that hysteresis of the
      spreading-receding cycle could arise from the contrasted dynamics between
      spreading and receding. A conceptual model of "offer and demand" which includes
      both the diffusivity gradient dD(rho)/d(rho) and the conditions applied at
      boundaries as main parameters is proposed to tentatively account for the dynamics
      of diffusive fronts in concentration-dependent diffusion processes.

PMID- 16089908
TI  - All-electron quantum Monte Carlo calculations for the noble gas atoms He to Xe.
AB  - We report all-electron variational and diffusion quantum Monte Carlo (VMC and
      DMC) calculations for the noble gas atoms He, Ne, Ar, Kr, and Xe. The
      calculations were performed using Slater-Jastrow wave functions with Hartree-Fock
      single-particle orbitals. The quality of both the optimized Jastrow factors and
      the nodal surfaces of the wave functions declines with increasing atomic number
      Z, but the DMC calculations are tractable and well behaved in all cases. We
      discuss the scaling of the computational cost of DMC calculations with Z.

PMID- 16089909
TI  - Wang-Landau sampling with self-adaptive range.
AB  - We report a self-adapting version of the Wang-Landau algorithm that is ideally
      suited for application to systems with a complicated structure of the density of
      states. Applications include determination of two-dimensional densities of states
      and high-precision numerical integration of sharply peaked functions on
      multidimensional integration domains.

PMID- 16089910
TI  - Finite-difference lattice-Boltzmann methods for binary fluids.
AB  - We investigate two-fluid Bhatnagar-Gross-Krook (BGK) kinetic methods for binary
      fluids. The developed theory works for asymmetric as well as symmetric systems.
      For symmetric systems it recovers Sirovich's theory and is summarized in models A
      and B. For asymmetric systems it contributes models C, D, and E which are
      especially useful when the total masses and/or local temperatures of the two
      components are greatly different. The kinetic models are discretized based on an
      octagonal discrete velocity model. The discrete-velocity kinetic models and the
      continuous ones are required to describe the same hydrodynamic equations. The
      combination of a discrete-velocity kinetic model and an appropriate finite
      difference scheme composes a finite-difference lattice Boltzmann method. The
      validity of the formulated methods is verified by investigating (i) uniform
      relaxation processes, (ii) isothermal Couette flow, and (iii) diffusion behavior.

PMID- 16089911
TI  - Optimization by quantum annealing: lessons from hard satisfiability problems.
AB  - The path integral Monte Carlo simulated quantum annealing algorithm is applied to
      the optimization of a large hard instance of the random satisfiability problem (N
      = 10,000). The dynamical behavior of the quantum and the classical annealing are
      compared, showing important qualitative differences in the way of exploring the
      complex energy landscape of the combinatorial optimization problem. At variance
      with the results obtained for the Ising spin glass and for the traveling salesman
      problem, in the present case the linear-schedule quantum annealing performance is
      definitely worse than classical annealing. Nevertheless, a quantum cooling
      protocol based on field-cycling and able to outperform standard classical
      simulated annealing over short time scales is introduced.

PMID- 16089912
TI  - Studying open quantum systems by means of a deterministic approach to approximate
      functional integration.
AB  - Representation of propagator for open quantum systems in the form of a double
      functional integral with respect to conditional Wiener measure is proposed. It
      allows one to apply the approximate formulas exact for functional polynomials of
      a certain power to calculation of such integrals. Within this deterministic
      approach the problem is reduced to evaluation of usual (Riemann) integrals of low
      multiplicity. The formulas are in fact the basis of a numerical method of
      studying time evolution of the systems. The features of the method are discussed
      and some examples of calculations are given.

PMID- 16089913
TI  - Diffuse-reflection boundary conditions for a thermal lattice Boltzmann model in
      two dimensions: evidence of temperature jump and slip velocity in microchannels.
AB  - We discuss the implementation of diffuse reflection boundary conditions in a
      thermal lattice Boltzmann model for which the upwind finite difference scheme is
      used to solve the set of evolution equations recovered after discretization of
      the velocity space. Simulation of heat transport between two parallel walls at
      rest shows evidence of temperature jumps at the walls that increase with Knudsen
      number. When the walls move in opposite directions with speeds +/- u(W), fluid
      velocity slip is observed at the walls, together with temperature jumps.

PMID- 16089914
TI  - Analytical investigation of innovation dynamics considering stochasticity in the
      evaluation of fitness.
AB  - We investigate a selection-mutation model for the dynamics of technological
      innovation, a special case of reaction-diffusion equations. Although mutations
      are assumed to increase the variety of technologies, not their average success
      ("fitness"), they are an essential prerequisite for innovation. Together with a
      selection of above-average technologies due to imitation behavior, they are the
      "driving force" for the continuous increase in fitness. We will give analytical
      solutions for the probability distribution of technologies for special cases and
      in the limit of large times. The selection dynamics is modeled by a "proportional
      imitation" of better technologies. However, the assessment of a technology's
      fitness may be imperfect and, therefore, vary stochastically. We will derive
      conditions under which a wrong assessment of fitness can accelerate the
      innovation dynamics, as has been found in some surprising numerical
      investigations.

PMID- 16089915
TI  - Resonant exit time in stochastic and deterministic systems.
AB  - The motion of a particle in the field of a time-dependent potential is studied
      here both at absolute zero and in the presence of thermal agitation. The
      potential executes either random fluctuations or deterministic harmonic
      oscillations. Assuming absorbing boundaries it is always possible to find an exit
      time tau(ex)(kappa) which has a local minimum as a function of the potential flip
      rate kappa. Thus resonant activation, usually associated with diffussive systems,
      exists in purely deterministic systems as well. Thermal agitation merely extends
      the range of admissible initial conditions and renders all exit times finite.

PMID- 16089916
TI  - 1/f(alpha) spectra in elementary cellular automata and fractal signals.
AB  - We systematically compute the power spectra of the one-dimensional elementary
      cellular automata introduced by Wolfram. On the one hand our analysis reveals
      that one automaton displays 1/f spectra though considered as trivial, and on the
      other hand that various automata classified as chaotic or complex display no 1/f
      spectra. We model the results generalizing the recently investigated Sierpinski
      signal to a class of fractal signals that are tailored to produce 1/f(alpha)
      spectra. From the widespread occurrence of (elementary) cellular automata
      patterns in chemistry, physics, and computer sciences, there are various
      candidates to show spectra similar to our results.

PMID- 16089917
TI  - Generalized synchronization: a modified system approach.
AB  - The universal mechanism resulting in the generalized synchronization regime
      arising in the chaotic oscillators with the dissipative coupling has been
      described. The reasons for the generalized synchronization occurrence may be
      clarified by means of a modified system approach. The main results are
      illustrated by unidirectionally coupled Rossler systems, Rossler and Lorenz
      systems, and logistic maps.

PMID- 16089918
TI  - Numerical simulation studies of the convective instability onset in a
      supercritical fluid.
AB  - Numerical simulation studies in 2D with the addition of noise are reported for
      the convection of a supercritical fluid, 3He , in a Rayleigh-Benard cell. The
      noise addition is to accelerate the instability growth after starting the heat
      flow across the fluid, so as to bring simulations into better agreement with
      published experimental observations. Homogeneous temperature noise and spatial
      longitudinal periodic temperature variations in either top or bottom plates were
      programmed into the simulations. The second method was the most effective in
      speeding up the instability onset. For a small amplitude of the longitudinal
      perturbations, a semiquantitative agreement with the observations was obtained.
      The results are discussed in relation to predictions by El Khouri and Carles.

PMID- 16089919
TI  - Formation and dynamics of finite amplitude localized pulses in elastic tubes.
AB  - We present theoretical and simulation studies of the formation and dynamics of
      finite-amplitude localized pulses (solitary waves) of an incompressible fluid in
      an elastic tube. Starting from a set of hydrodynamic equations, we derive a
      Hamiltonian which represents the energy integral of our system. The energy
      integral is analyzed to obtain explicit profiles of finite-amplitude solitary
      pulses. Also studied are the excitation and dynamics of solitary pulses by using
      computer simulations. It is found that a train of solitary pulses can be excited
      by the nonlinear self-steepening at shock fronts. The relevance of our
      investigation to blood solitary waves in arteries is discussed.

PMID- 16089920
TI  - Model flames in the Boussinesq limit: the case of pulsating fronts.
AB  - We extend earlier work on the nonlinear behavior of premixed flames in a
      gravitationally stratified medium, subject to the Boussinesq approximation, in
      two dimensions. The main result is that the nature of the traveling burning front
      is largely determined by the form of the adopted boundary conditions on the side
      walls: while symmetric boundary conditions lead to stably scalloped traveling
      wave solutions, loss of symmetry leads to the development of pulsating fronts.
      However, despite differences in geometrical features, the symmetric and
      asymmetric systems obey the same scaling behavior for the average effective flame
      speed.

PMID- 16089921
TI  - Evolution of a passive scalar spectrum in the flow of random waves.
AB  - We consider a passive pollutant advected by the flow due to linear random waves
      with finite attenuation. We derive the equation that governs the evolution of the
      pair correlation function of pollutant concentration and show that it coincides
      with the equation for the case of a short-correlated velocity. Due to a finite
      wave attenuation, nontrivial evolution (particularly, the growth of
      inhomogeneities) appears already in the second order in wave amplitudes. We show
      that random potential waves lead to the growth of concentration inhomogeneities.
      We identify two stationary solutions for the spectral density of concentration,
      equipartition, and flux state. Which one is established depends on the relation
      between mean square velocity gradients due to potential and solenoidal parts of
      the flow, respectively. We also analyze transient regimes and show how periodic
      component in the concentration distribution appears and disappears.

PMID- 16089922
TI  - Second- and third-harmonic generations in compositionally graded films.
AB  - We present a theoretical description of the effective nonlinear susceptibilities
      for second-harmonic generation (SHG) and third-harmonic generation (THG) of
      compositionally graded films, in which one of the components possesses non
      vanishing second- and third-order nonlinear susceptibilities. We first resort to
      the nonlinear effective medium approximation to obtain the equivalent (local)
      second- and third-order nonlinear susceptibilities in a z slice. Then, the
      formulas for effective nonlinear SHG and THG susceptibilities of the graded film
      are directly established, if we regard the graded film as the limit of a
      multilayer one. Numerical results show that if the electric field is polarized
      perpendicular to the plane of layers, both effective SHG and THG susceptibilities
      for graded profiles are larger than those for non-graded ones. Furthermore, for a
      given total volume fraction p , the adjustment of compositional gradient results
      in a large enhancement of effective SHG and THG especially in the high-frequency
      region. Therefore, the compositionally graded films can be served as a noval
      candidate material for obtaining the optimal SHG and THG susceptibilities.

PMID- 16089923
TI  - Traveling salesman problem with a center.
AB  - We study a traveling salesman problem where the path is optimized with a cost
      function that includes its length L as well as a certain measure C of its
      distance from the geometrical center of the graph. Using simulated annealing (SA)
      we show that such a problem has a transition point that separates two phases
      differing in the scaling behavior of L and C, in efficiency of SA, and in the
      shape of minimal paths.

PMID- 16089924
TI  - Natural cutoff in Levy flights caused by dissipative nonlinearity.
AB  - Levy flight models are often used to describe stochastic processes in complex
      systems. However, due to the occurrence of diverging position and/or velocity
      fluctuations Levy flights are physically problematic if describing the dynamics
      of a particle of finite mass. Here we show that the velocity distribution of a
      random walker subject to Levy noise can be regularized by nonlinear friction,
      leading to a natural cutoff in the velocity distribution and finite velocity
      variance.

PMID- 16089925
TI  - Spatially heterogeneous dynamics in a model for granular compaction.
AB  - We suggest the emergence of spatially correlated dynamics in slowly compacting
      dense granular media by analyzing analytically and numerically multipoint
      correlation functions in a simple particle model characterized by slow
      nonequilibrium dynamics. We show that the logarithmically slow dynamics at large
      times is accompanied by spatially extended dynamic structures that resemble the
      ones observed in glass-forming liquids and dense colloidal suspensions. This
      suggests that dynamic heterogeneity is another key common feature present in very
      different jamming materials.

PMID- 16089926
TI  - Interactions between nanoparticles in supercritical fluids: from repulsion to
      attraction.
AB  - We present a density functional theory study of interactions between sterically
      stabilized spherical nanoparticles in a supercritical solvent. The theory is used
      to analyze the effect of particle size, solvent density, and solvent-ligand
      interaction strength on the potential of mean force between the particles.
      Experimentally observed size-selective precipitation of nanoparticles is
      rationalized in terms of the behavior of the density profiles of stabilizing
      ligands as a function of particle size and solvent thermodynamic conditions. The
      theory yields the same general trends as observed in experiments, namely, an
      increased stability of nanoparticle dispersions at higher solvent densities and
      for smaller particle sizes.

PMID- 16089927
TI  - Demixing can occur in binary hard-sphere mixtures with negative nonadditivity.
AB  - A binary fluid mixture of nonadditive hard spheres characterized by a size ratio
      gamma = sigma(2)/sigma(1) < 1 and a nonadditivity parameter Delta = 2
      sigma(12)/(sigma(1) + sigma(2)) - 1 is considered in infinitely many dimensions.
      From the equation of state in the second virial approximation (which is exact in
      the limit d--> infinity) a demixing transition with a critical consolute point at
      a packing fraction scaling as eta approximately d2(-d) is found, even for
      slightly negative nonadditivity, if Delta >-1/8 (ln gamma)(2). Arguments
      concerning the stability of the demixing with respect to freezing are provided.

PMID- 16089928
TI  - Modulated phase of phospholipids with a two-dimensional square lattice.
AB  - We report an observation of a modulated phase of phospholipids in which
      intrabilayer density modulations form an in-plane square lattice. Similar to the
      well-known ripple (P'(beta)) phase, this phase can be induced by either
      dehydration or cooling from the liquid crystalline (L(alpha)) phase. However,
      further lowering of hydration or temperature induces either an untilted straight
      chain gel phase (L(beta)) , or the tilted L'(beta) phase after a brief appearance
      of the P'(beta) phase. The structural characteristics of this phase support the
      notion that the coupling between variations in local chain tilt and bilayer shape
      plays an important role in the formation of modulated phases.

PMID- 16089929
TI  - Structural origin of the brown color of barbules in male peacock tail feathers.
AB  - We report detailed optical measurements and numerical simulations of brown
      barbules in male peacock tail feathers. Our results indicate that brown
      coloration is predominantly produced structurally by the two-dimensional (2D)
      photonic-crystal structure in the cortex layer of a barbule. The constructing
      strategies of brown coloration revealed by numerical simulations are indeed
      subtle, which are of great significance in the artificial constructions of mixed
      structural coloration. It is found that the structural configurations of the 2D
      photonic-crystal structure such as the lattice constant, the number of periods,
      and even the interdistance and missing holes between the two melanin layers
      nearest to the cortex surface, are important in the production of structural
      brown colors.

PMID- 16089930
TI  - Distinctive features of the biological catch bond in the jump-ramp force regime
      predicted by the two-pathway model.
AB  - The receptor-ligand unbinding in the biological catch bond is analyzed within a
      simple model that comprises a single bound state and two unbinding pathways. This
      model is investigated in detail for the jump-ramp force regime, where the pulling
      force quickly jumps to a finite value and then is ramped linearly with time. Two
      qualitative criteria are identified that distinguish the catch bond from the slip
      bond. First, the rupture force probability density of the catch-bond exhibits a
      maximum-minimum pair, which develops at finite forces. In contrast, the slip bond
      produces a maximum that first appears at zero force. Second, the catch bond can
      be identified over a wide range of ramp rates by high rupture probabilities at
      low forces relative to the probability at the maximum, in contrast to the slip
      bond, where the probability at the maximum always corresponds to the most likely
      rupture force. Both distinctive features of the catch bond are masked by large
      jump forces, indicating that the catch bond is best identified in experiments
      with moderate loading rates and small jump forces. The catch-bond lifetime in the
      constant force regime is related to the probability density in the jump-ramp
      regime, allowing one to determine the bond lifetime for a constant force by
      measuring the initial probability density in the jump-ramp experiments with
      different jump forces and a fixed ramp rate. The key analytic results are
      illustrated with the P -selectin/P-selectin glucoprotein ligand-1 bond.

PMID- 16089931
TI  - Power law tails of time correlations in a mesoscopic fluid model.
AB  - In a quenched mesoscopic fluid, modeling transport processes at high densities,
      we perform computer simulations of the single particle energy autocorrelation
      function C(e) (t) , which is essentially a return probability. This is done to
      test the predictions for power law tails, obtained from mode coupling theory. We
      study both off and on-lattice systems in one- and two-dimensions. The predicted
      long time tail approximately t(-d/2) is in excellent agreement with the results
      of computer simulations. We also account for finite size effects, such that
      smaller systems are fully covered by the present theory as well.

PMID- 16089932
TI  - Configurational entropy and its crisis in metastable states: ideal glass
      transition in a dimer model as a paragidm of a molecular glass.
AB  - We discuss the need for discretization to evaluate the configurational entropy in
      a general model. We also discuss the prescription using restricted partition
      function formalism to study the stationary limit of metastable states where a
      more stable equilibrium state exists. We introduce a lattice model of dimers as a
      paradigm of molecular fluid and study stationary metastability in it to
      investigate the root cause of glassy behavior. We demonstrate the existence of
      entropy crisis in metastable states, from which it follows that the entropy
      crisis is the root cause underlying the ideal glass transition in systems with
      particles of all sizes. The orientational interactions in the model control the
      nature of the liquid-liquid transition observed in recent years in molecular
      glasses.

PMID- 16089933
TI  - Fractional rotational diffusion of rigid dipoles in an asymmetrical double-well
      potential.
AB  - The longitudinal and transverse components of the complex dielectric
      susceptibility tensor of an assembly of dipolar molecules rotating in an
      asymmetric double-well potential are evaluated using a fractional rotational
      diffusion equation (based on the diffusion limit of a fractal time random walk)
      for the distribution function of orientations of the molecules on the surface of
      the unit sphere. The calculation is the fractional analog of the Debye theory of
      orientational relaxation in the presence of external and mean field potentials
      (excluding inertial effects). Exact and approximate (based on the exponential
      separation for normal diffusion of the time scales of the intrawell and
      overbarrier relaxation processes associated with the bistable potential)
      solutions for the dielectric dispersion and absorption spectra are obtained. It
      is shown that a knowledge of the characteristic relaxation times for normal
      rotational diffusion is sufficient to predict accurately the anomalous dielectric
      relaxation behavior of the system for all time scales of interest. The model
      explains the anomalous (Cole-Cole-like) relaxation of complex dipolar systems,
      where the anomalous exponent differs from unity (corresponding to the normal
      dielectric relaxation), i.e., the relaxation process is characterized by a broad
      distribution of relaxation times (e.g., in glass-forming liquids).

PMID- 16089934
TI  - Fluctuation-dissipation relations for Markov processes.
AB  - The fluctuation-dissipation relation is calculated for stochastic models obeying
      a master equation with continuous time. In the general case of a nonstationary
      process, there appears to be no simple relation between the response and the
      correlation. Also, if one considers stationary processes, the linear response
      cannot be expressed via time-derivatives of the correlation function alone. In
      this case, an additional function, which has rarely been discussed previously, is
      required. This so-called asymmetry depends on the two times also relevant for the
      response and the correlation and it vanishes under equilibrium conditions. The
      asymmetry can be expressed in terms of the propagators and the transition rates
      of the master equation but it is not related to any physical observable in an
      obvious way. It is found that the behavior of the asymmetry strongly depends on
      the nature of the dynamical variable considered in the calculation of the
      correlation and the response. If one is concerned with a variable which
      randomizes with any transition among the states of the system, the asymmetry
      vanishes in most cases. This is in contrast to the situation for other classes of
      variables. In particular, for trap models of glassy relaxation, the fluctuation
      dissipation ratio strongly depends on the observable and the asymmetry plays a
      dominant role in the determination of this ratio also if only neutral variables
      are considered. Some implications of a nonvanishing asymmetry with regard to the
      definition of an effective temperature are discussed.

PMID- 16089935
TI  - Long-time dynamics of the three-dimensional biaxial Grinfeld instability.
AB  - Using a phase-field model including strain fields, we numerically investigate the
      melting-crystallization dynamics of a biaxially stressed semi-infinite solid. A
      multigrid algorithm is used to solve the elasticity part of the problem. Its
      efficiency allows us to explore the late stages of the full 3D Grinfeld
      instability. Recent analytical predictions [P. Berger, Phys. Rev. Lett. 90,
      176103 (2003)] regarding stability and selection of patterns are confirmed and
      precised. It appears that, in the presence of a large scale stabilization
      mechanism, the system reaches an equilibrium state corresponding to a nontrivial
      striped pattern.

PMID- 16089936
TI  - Exactly solvable model of continuous stationary 1/f noise.
AB  - An exactly solvable model generating a continuous random process with a 1/f power
      spectrum is presented. Examples of such processes include the angular (phase)
      speed of trajectories near stable equilibrium points in two-dimensional dynamical
      systems perturbed by colored Gaussian noise. An exact formula giving the
      correlation function of the 1/f noise in terms of the correlation of the
      perturbing colored noises is derived, and used to show that the 1/f spectrum is
      found in a wide variety of cases. The 1/f noise is non-Gaussian, as demonstrated
      by calculating its one-time probability distribution function. Numerical
      simulations confirm and extend the theoretical results.

PMID- 16089937
TI  - Time-fractional diffusion equation with time dependent diffusion coefficient.
AB  - We consider the time-fractional diffusion equation with time dependent diffusion
      coefficient given by (O)O(alpha)(C)(t) W (x,t) = D(alpha,gamma)(t)(gamma)
      [theta(2) W (x,t) /theta x(2)], where O is the Caputo operator. We investigate
      its solutions in the infinite and the finite domains. The mean squared
      displacement and the mean first passage time are also considered. In particular,
      for alpha = 0 , the mean squared displacement is given by <x(2)> approximately
      t(gamma) and we verify that the mean first passage time is finite for
      superdiffusive regimes.

PMID- 16089938
TI  - Driven classical diffusion with strong correlated disorder.
AB  - For driven classical diffusion quenched by a strong potential disorder V(x), we
      identify a prominent crossover regime between the regimes of very small and very
      large driving forces F, where the corresponding mobility values mu (F) differ
      exponentially. For disorder with power-law correlations at large distances <V(x)
      (y) approximately |x - y|(-n), n > 0, the crossover is characterized by power-law
      dependence of the logarithm of mu (F) on the driving force ln mu (F)
      approximately F(n/(n + 1)). For finite-range disorder (formally, n = infinity),
      the corresponding dependence is linear ("logarithmic susceptibility").

PMID- 16089939
TI  - Interpretation of a fractional diffusion equation with nonconserved probability
      density in terms of experimental systems with trapping or recombination.
AB  - The fractional diffusion equation that is constructed replacing the time
      derivative with a fractional derivative, (0)D(alpha)(t) f = C(alpha) theta(2)
      f/theta x(2), where (0)D(alpha)(t) is the Riemann-Liouville derivative operator,
      is characterized by a probability density that decays with time as t(alpha -1)
      (alpha < 1) and an initial condition that diverges as t -->0 [R. Hilfer, J. Phys.
      Chem. B 104, 3914 (2000)]. These seemingly unphysical features have obstructed
      the application of the fractional diffusion equation. The paper clarifies the
      meaning of these properties adopting concrete physical interpretations of
      experimentally verified models: the decay of free-carrier density in a
      semiconductor with an exponential distribution of traps, and the decay of ion
      recombination isothermal luminescence. We conclude that the fractional diffusion
      equation is a suitable representation of diffusion in disordered media with
      dissipative processes such as trapping or recombination involving an initial
      exponential distribution either in the energy or spatial axis. The fractional
      decay does not consider explicitly the starting excitation and ultrashort time
      scale relaxation that forms the initial exponential distribution, and therefore
      it cannot be extrapolated to t = 0.

PMID- 16089940
TI  - Noise-induced escape of periodically modulated systems: from weak to strong
      modulation.
AB  - Noise-induced escape from a metastable state is studied for an overdamped
      periodically modulated system. We develop an asymptotic technique that gives both
      the instantaneous and period-average escape rates, including the prefactor, for
      an arbitrary modulation amplitude A . We find the parameter range where escape is
      strongly synchronized and the instantaneous escape rate displays sharp peaks. The
      peaks vary with increasing modulation frequency or amplitude from Gaussian to
      strongly asymmetric. The prefactor nu in the period-average escape rate depends
      on A nonmonotonically. Near the bifurcation amplitude A(c) it scales as nu
      approximately (A(c) - A)(zeta). We identify three scaling regimes, with zeta =
      1/4, -1, and 1/2.

PMID- 16089941
TI  - Necessary criterion for distinguishing true superdiffusion from correlated random
      walk processes.
AB  - A difficulty in interpreting phenomena related to anomalous diffusion concerns
      how to identify scale invariant superdiffusive from Markovian correlated random
      walk processes. Here we propose a criterion that can distinguish between these
      two kinds of random walks and describe its usefulness in interpreting real data.
      To do so, we estimate the correlation time tau of the orientation persistence of
      a general correlated random walk. If the experimentally observed random walk
      appears diffusive on scales larger than tau, then the data cannot support the
      possibility of superdiffusion. We argue that the criterion is a necessary but not
      sufficient condition for establishing true superdiffusive behavior.

PMID- 16089942
TI  - Delay Fokker-Planck equations, Novikov's theorem, and Boltzmann distributions as
      small delay approximations.
AB  - We study time-delayed stochastic systems that can be described by means of so
      called delay Fokker-Planck equations. Using Novikov's theorem, we first show that
      the theory of delay Fokker-Planck equations is on an equal footing with the
      theory of ordinary Fokker-Planck equations. Subsequently, we derive stationary
      distributions in the case of small time delays. In the case of additive noise
      systems, these distributions can be cast into the form of Boltzmann distributions
      involving effective potential functions.

PMID- 16089943
TI  - Harmonic velocity noise: non-Markovian features of noise-driven systems at long
      times.
AB  - We propose a harmonic velocity noise with a broadband feature, which is the time
      derivative of the harmonic noise. If this noise is regarded as a thermal one, the
      system has a vanishing effective friction and it should induce ballistic
      diffusion of a free particle at long times. The effective temperature of the
      system coupled to such a structured heat bath represented by the harmonic
      velocity noise is introduced. This means that any initial preparation will
      approach asymptotically a preparation-dependent variance and mean value for
      velocity variable. Thus the fluctuation-dissipation theorem does not hold as
      there is no unique stationary state being connected with a breakdown of
      ergodicity. This noise can show greenness when it is taken as an external noise
      source to drive a correlation ratchet.

PMID- 16089944
TI  - Optimizing the bulk modulus of low-density cellular networks.
AB  - We present an alternative derivation of upper-bounds for the bulk modulus of both
      two-dimensional and three-dimensional cellular materials. For two-dimensional
      materials, we recover exactly the expression of the Hashin-Shtrikman (HS) upper
      bound in the low-density limit, while for three-dimensional materials we even
      improve the HS bound. Furthermore, we establish necessary and sufficient
      conditions on the cellular structure for maximizing the bulk modulus, for a given
      solid volume fraction. The conditions are found to be exactly those under which
      the electrical (or thermal) conductivity of the material reaches its maximal
      value as well. These results provide a set of straightforward criteria allowing
      us to address the design of optimized cellular materials, and shed light on
      recent studies of structures with both maximal bulk modulus and maximal
      conductivity. Finally, we discuss the specific case of spring networks, and
      analyze the compatibility of the criteria presented here with the geometrical
      constraints caused by minimization of surface energy in a real foam.

PMID- 16089945
TI  - Asymmetric nanodiffusion.
AB  - The asymmetric diffusion through conical nanopores is described by the
      diffusional model. Diffusion is several times faster; when the concentration
      gradient points from the wide towards the narrow opening of the cone than in the
      opposite direction. The asymmetric diffusion appears either when the diffusion
      coefficient depends on the concentration or when the diffusing substances
      interact with the channel (i.e., ions moving through channels with charged
      walls). These results suggest that asymmetric nanopores can act as molecular
      (ionic) filters which could be used for retrieving the molecules of a given
      component from solutions in which its concentration fluctuates strongly, and only
      occasionally attains high values.

PMID- 16089946
TI  - Clusters of mobile molecules in supercooled water.
AB  - We study the spatially heterogeneous dynamics in water via molecular dynamics
      simulations using the extended simple point charge potential. We identify
      clusters formed by mobile molecules and study their properties. We find that
      these clusters grow in size and become more compact as temperature decreases. We
      analyze the probability density function of cluster size, and we study the
      cluster correlation length. We find that clusters appear to be characterized by a
      fractal dimension consistent with that of lattice animals. We relate the cluster
      size and correlation length to the configurational entropy, S(conf). We find that
      these quantities depend weakly on 1/ S(conf). In particular, the linearity found
      between the cluster mass n(*) and 1/ S(conf) suggests that n(*) may be
      interpreted as the mass of the cooperatively rearranging regions that form the
      basis of the Adam-Gibbs approach to the dynamics of supercooled liquids. We study
      the motion of molecules within a cluster, and find that each molecule
      preferentially follows a neighboring molecule in the same cluster. Based on this
      finding we hypothesize that stringlike cooperative motion may be a general
      mechanism for molecular rearrangement of complex, as well as simple liquids. By
      mapping each equilibrium configuration onto its corresponding local potential
      energy minimum or inherent structure (IS), we are able to compare the mobile
      molecule clusters in the equilibrium system with the molecules forming the
      clusters identified in the transitions between IS. We find that (i) mobile
      molecule clusters obtained by comparing different system configurations and (ii)
      clusters obtained by comparing the corresponding IS are completely different for
      short time scales, but are the same on the longer time scales of diffusive
      motion.

PMID- 16089947
TI  - Structural relaxation in the glass transition region of water.
AB  - We perform molecular dynamics (MD) simulations using the extended simple-point
      charge (SPC/E) model for water to study the structural relaxation through the
      glass transition region. We follow the same standard protocol used in
      differential scanning calorimetry experiments. Specifically, we cool liquid
      configurations at different cooling rates to produce a glass, and then we heat
      the glass back to the liquid state. We also study aging effects in the glass
      before heating. We find that MD simulations can reproduce the phenomenology
      observed in experiments. We review the Tool-Narayanaswamy-Moynihan (TNM)
      phenomenological approach, introduced to describe the behavior of the specific
      heat upon heating glass to the liquid phase. The TNM approach requires, as an
      ansatz, an expression for the temperature dependence of the relaxation time. We
      compare the simulation results with the prediction of the TNM approach
      supplemented with two well-known expressions for the relaxation time: the
      Narayanaswamy-Moynihan (NM) and the Adam-Gibbs-Scherer (AGS) expressions. We find
      that, in the case of slow cooling rates, our simulations are well represented by
      the TNM approach, but only if the AGS expression is adopted. We also find that
      the TNM approach fails in the case of fast cooling rates for both NM and AGS
      expressions. Several attempts to provide more freedom to the fitting procedure by
      allowing the fitting parameters to depend on temperature, cooling, and/or heating
      rates do not improve the agreement between the simulation data and the TNM
      predictions.

PMID- 16089948
TI  - Closed form for the equations of chemically reacting flows under local
      thermodynamic equilibrium.
AB  - We present a closed form for the governing equations of chemically reacting flows
      under local thermodynamic equilibrium, which rigorously takes into account
      effects of elemental (de)mixing. To this end, we show that when chemistry is
      fast, the diffusion fluxes of elements and species enthalpies can be expressed as
      explicit linear functions of gradients of elemental mass fractions and
      temperature. Our formulation is a natural extension of classical work on local
      equilibrium flows by other authors and yields results equivalent with a recent
      fully rigorous mathematical theory in a straightforward and physically appealing
      manner. The obtained set of equations is well-suited for numerical
      implementations and does not require the computationally expensive evaluation of
      thermodynamic derivatives using finite differences. The new transport
      coefficients that appear in the equations allow quantitative predictions and help
      to gain deeper insight into the physics of chemically reacting flows at and near
      local equilibrium.

PMID- 16089949
TI  - Relaxation in a glassy binary mixture: mode-coupling-like power laws, dynamic
      heterogeneity, and a new non-Gaussian parameter.
AB  - We examine the relaxation of the Kob-Andersen Lennard-Jones binary mixture using
      Brownian dynamics computer simulations. We find that in accordance with mode
      coupling theory the self-diffusion coefficient and the relaxation time show power
      law dependence on temperature. However, different mode-coupling temperatures and
      power laws can be obtained from the simulation data depending on the range of
      temperatures chosen for the power-law fits. The temperature that is commonly
      reported as this system's mode-coupling transition temperature, in addition to
      being obtained from a power law fit, is a crossover temperature at which there is
      a change in the dynamics from the high-temperature homogeneous, diffusive
      relaxation to a heterogeneous, hopping-like motion. The hopping-like motion is
      evident in the probability distributions of the logarithm of single-particle
      displacements: approaching the commonly reported mode-coupling temperature these
      distributions start exhibiting two peaks. Notably, the temperature at which the
      hopping-like motion appears for the smaller particles is slightly higher than
      that at which the hopping-like motion appears for the larger ones. We define and
      calculate a new non-Gaussian parameter whose maximum occurs approximately at the
      time at which the two peaks in the probability distribution of the logarithm of
      displacements are most evident.

PMID- 16089950
TI  - Jamming transition in emulsions and granular materials.
AB  - We investigate the jamming transition in packings of emulsions and granular
      materials via molecular dynamics simulations. The emulsion model is composed of
      frictionless droplets interacting via nonlinear normal forces obtained using
      experimental data acquired by confocal microscopy of compressed emulsions
      systems. Granular materials are modeled by Hertz-Mindlin deformable spherical
      grains with Coulomb friction. In both cases, we find power-law scaling for the
      vanishing of pressure and excess number of contacts as the system approaches the
      jamming transition from high volume fractions. We find that the construction
      history parametrized by the compression rate during the preparation protocol has
      a strong effect on the micromechanical properties of granular materials but not
      on emulsions. This leads the granular system to jam at different volume fractions
      depending on the histories. Isostaticity is found in the packings close to the
      jamming transition in emulsions and in granular materials at slow compression
      rates and infinite friction. Heterogeneity of interparticle forces increases as
      the packings approach the jamming transition which is demonstrated by the
      exponential tail in force distributions and the small values of the participation
      number measuring spatial localization of the forces. However, no signatures of
      the jamming transition are observed in structural properties, like the radial
      distribution functions and the distributions of contacts.

PMID- 16089951
TI  - Jamming transition in a highly dense granular system under vertical vibration.
AB  - The dynamics of the jamming transition in a three-dimensional granular system
      under vertical vibration is studied using diffusing-wave spectroscopy. When the
      maximum acceleration of the external vibration is large, the granular system
      behaves like a fluid, with the dynamic correlation function G (t) relaxing
      rapidly. As the acceleration of vibration approaches the gravitational
      acceleration g , the relaxation of G (t) slows down dramatically, and eventually
      stops. Thus the system undergoes a phase transition and behaves like a solid.
      Near the transition point, we find that the structural relaxation shows a
      stretched exponential behavior. This behavior is analogous to the behavior of
      supercooled liquids close to the glass transition.

PMID- 16089952
TI  - Hydrodynamic modes for a granular gas from kinetic theory.
AB  - Small perturbations of the homogeneous cooling state for a low density granular
      gas are described by means of the linearized Boltzmann equation. The spectrum of
      the generator for this dynamics is shown to contain points corresponding to
      hydrodynamic excitations. The corresponding eigenvectors and eigenvalues are
      calculated to Navier-Stokes order and shown to agree with those obtained by the
      Chapman-Enskog method. The conditions for the hydrodynamic excitations to
      dominate all other excitations are discussed.

PMID- 16089953
TI  - Effect of air on granular size separation in a vibrated granular bed.
AB  - Using high-speed video and magnetic resonance imaging (MRI) we study the motion
      of a large sphere in a vertically vibrated bed of smaller grains. As previously
      reported we find a nonmonotonic density dependence of the rise and sink time of
      the large sphere. We show that air drag causes relative motion between the
      intruder and the bed during the shaking cycle and is ultimately responsible for
      the observed density dependence of the risetime. We investigate in detail how the
      motion of the intruder sphere is influenced by size of the background particles,
      initial vertical position in the bed, ambient pressure, and convection. We
      explain our results in the framework of a simple model and find quantitative
      agreement in key aspects with numerical simulations to the model equations.

PMID- 16089954
TI  - Friction and convection in a vertically vibrated granular system.
AB  - The effect of friction in the thermal convection instability of granular fluids
      is studied by means of molecular dynamics simulations. It is found that the
      transitions between different convective states (zero, one, and two rolls) are
      primarily governed by the average energy loss per collisions and not by the
      friction and restitution coefficients separately, and can be roughly described in
      terms of a single effective restitution coefficient. The average energy loss per
      collisions, for a fixed value of the restitution coefficient, shows a maximum for
      a friction coefficient kappa approximately 0.3. The presence of this maximum
      manifests itself as a reentrant behavior in the transition lines in parameter
      space when the value of the friction coefficient is increased beyond 0.3.

PMID- 16089955
TI  - Aging of a colloidal glass under a periodic shear.
AB  - The aging dynamics under a periodic shear of a concentrated suspension of
      saponite particles is measured. It is observed that the dynamics is fastened by
      the application of a moderate shear amplitude. Nevertheless, this acceleration
      does not affect the dynamics of the suspension when the shear is ceased. By
      applying a succession of shear of various amplitudes, we conclude that the
      dynamics of the suspension at a time t(w) after complete rejuvenation is
      independent of the shear history between times 0 and t(w) , as soon as the
      amplitude of the applied shear is smaller than the characteristic shear gamma(c)
      necessary to completely rejuvenate the suspension.

PMID- 16089956
TI  - Crackling of a coagulating suspension.
AB  - A way of analyzing the intermittent dynamics of nonstationary systems is
      introduced. It is used to study the dynamics of a concentrated suspension while
      it is flocculating, probed by diffusing wave spectroscopy. When the repulsion
      interactions between the particles are slowly decreased their motion appears to
      be intermittent. It is characterized by rapid crackling periods, separated by
      arrested dynamics. Duration of the crackling periods exhibit a power-law
      distribution function.

PMID- 16089957
TI  - Successive exponential and full aging regimes evidenced by tracer diffusion in a
      colloidal glass.
AB  - We study the aging of a colloidal laponite glass by measuring the dynamic
      structure factor of dilute embedded tracer particles on micrometric length
      scales. We show that an initial aging regime, where the decay time grows
      exponentially with aging time t(w), tau approximately exp (gamma t(w)), is
      followed by a full aging regime, tau approximately t(v)(w) with v approximately
      1. The dynamics of the tracers is diffusive in the exponential regime and
      hyperdiffusive in the full aging regime, up to micrometric length scales.

PMID- 16089959
TI  - Structure and dynamics of repulsive magnetorheological colloids in two
      dimensional channels.
AB  - We study a system of colloidal spheres with induced magnetic dipoles confined in
      two-dimensional (2D) hard-wall channels using Brownian dynamics simulations. The
      external magnetic field is directed normal to the 2D plane and therefore the
      colloids interact with a purely repulsive r(-3) potential. The effects of
      confinement between parallel walls are determined by analyzing the structure and
      dynamics of these confined systems and comparing to the unbounded (infinite) 2D
      plane limit. The bond-order correlation function is analyzed as a function of
      time and exhibits unique characteristics associated with the channel-like
      confinement. The existence of a plateau in this correlation function is observed
      over an intermediate time scale and the fate of the plateau (decay or
      persistence) depends upon the channel width, the strength of the external
      magnetic field, and the number density. The plateau is analyzed in further detail
      and an explanation is put forth for its existence and subsequent long time
      behavior. Additionally, re-entrant behavior with respect to dimensionless channel
      width is observed in the structural properties and an associated state-diagram is
      presented for these systems.

PMID- 16089958
TI  - Growth of monodisperse mesoscopic metal-oxide colloids under constant monomer
      supply.
AB  - In closed systems, control over the size of monodisperse metal-oxide colloids is
      generally limited to submicrometric dimensions. To overcome this difficulty, we
      explore the formation and growth of silica particles under constant monomer
      supply. The monomer source is externally driven by the progressive addition into
      the system of one of the precursors. Monodisperse spherical particles are
      produced up to a mesoscopic size. We analyze their growth versus the monomer
      addition rate at different temperatures. Our results show that in the presence of
      a continuous monomer addition, growth is limited by diffusion over the
      investigated temporal window. Using the temperature variation of the growth rate,
      we prove that rescaling leads to a data reduction onto a single master curve.
      Contrary to the growth process, the final particle's size reached after the end
      of the reagent supply strongly depends on the addition rate. The variation of the
      final particle size versus addition rate can be deduced from an analogy with
      crystal formation in jet precipitation. Within this framework, and using the
      temperature dependences of both the particle growth law and the final size, we
      determine the value of the molecular heat of dissolution associated to the silica
      solubility. These observations support the fact that classical theories of phase
      ordering dynamics can be extended to the synthesis of inorganic particles. The
      emergence of a master behavior in the presence of continuous monomer addition
      also suggests the extension of these theories to open systems.

PMID- 16089960
TI  - Fractal dimension and unscreened angles measured for radial viscous fingering.
AB  - We have examined fractal patterns formed by the injection of air into oil in a
      thin (0.127 mm) layer contained between two cylindrical glass plates of 288 mm
      diameter (a Hele-Shaw cell), for pressure differences in the range 0.25 < or =
      DeltaP < or = 1.75 atm. We find that an asymptotic structure is reached at large
      values of the ratio r/b, where r is the pattern radius and b the gap between the
      plates. Both the driving force and the size of the pattern, which reaches r/b =
      900, are far larger than in past experiments. The fractal dimension D0 of the
      pattern for large r/b is 1.70 +/- 0.02. Further, the generalized dimensions D(q)
      of the pattern are independent of q , D(q) approximately 1.70 for the range
      examined, -11 < q < 17; thus the pattern is self-similar within the experimental
      uncertainty. The results for D(q) agree well with recent calculations for
      diffusion-limited aggregation (DLA) clusters. We have also measured the
      probability distribution of unscreened angles. At late times, the distribution
      approaches a universal (i.e., forcing and size-independent) asymptotic form that
      has mean 145 degrees Celsius and standard deviation 36 degrees Celsius. These
      results indicate that the distribution function for the unscreened angle is an
      invariant property of the growth process.

PMID- 16089961
TI  - Depletion interaction in a quasi-two-dimensional binary colloid mixture: Monte
      Carlo simulations.
AB  - We report the results of extensive calculations of the depletion interaction
      between the large hard spheres in a quasi-two-dimensional (q2D) binary mixture of
      large and small hard spheres. Two definitions of the depletion interaction have
      been examined, and the dependencies of both on the large and small sphere
      densities, and the confining wall separation have been explored. The results of
      the simulations show that the depletion interaction is enhanced relative to its
      magnitude in a three-dimensional binary mixture with the same density,
      composition and sphere diameter ratio and that it has a complex dependence on the
      large sphere-large sphere separation. There are qualitative differences between
      the properties of q2D and mathematical 2D systems that are relevant to the
      interpretation of experimental data.

PMID- 16089962
TI  - Simulation of claylike colloids.
AB  - We investigate the properties of dense suspensions and sediments of small
      spherical silt particles by means of a combined molecular dynamics and stochastic
      rotation dynamics (SRD) simulation. We include van der Waals and effective
      electrostatic interactions between the colloidal particles, as well as Brownian
      motion and hydrodynamic interactions which are calculated in the SRD part. We
      present the simulation technique and first results. We have measured velocity
      distributions, diffusion coefficients, sedimentation velocity, spatial
      correlation functions, and we have explored the phase diagram depending on the
      parameters of the potentials and on the volume fraction.

PMID- 16089963
TI  - Surface relaxation and chemical exchange in hydrating cement pastes: a two
      dimensional NMR relaxation study.
AB  - We report the first nuclear magnetic resonance (NMR) two-dimensional correlation
      T(1) - T(2) and T(2) - T(2) measurements of hydrating cement pastes. A small but
      distinct cross peak in the two-dimensional relaxation spectrum provides the first
      direct evidence of chemical exchange of water between gel and capillary pores
      occurring over the first 14 days of hydration. A correlation of features along
      the line T(1) = 4T(2) provides strong supportive evidence for the surface
      diffusion model of (1)H nuclear spin relaxation in cements and for a multimodal
      discrete pore size distribution. Differences in detail of the results are
      reported for white cement paste and white cement paste with added silica fume.
      Both the method and the theory presented can be applied more widely to other high
      surface area materials with other reactive surface areas.

PMID- 16089964
TI  - Solidity of viscous liquids. III. alpha relaxation.
AB  - It is suggested that the omega(-1/2) high-frequency decay of the alpha loss in
      highly viscous liquids, which appears to be generic, is a manifestation of a
      negative long-time tail as typically encountered in stochastic dynamics. The
      proposed mechanism requires that the coherent diffusion constant is much larger
      than estimated from the alpha relaxation time. This is justified by reference to
      the solidity of viscous liquids in an argument which, by utilizing the
      irrelevance of momentum conservation at high viscosity and introducing a center
      of mass diffusion constant, implies that at high viscosity the coherent diffusion
      constant is much larger than the incoherent diffusion constant.

PMID- 16089965
TI  - Kinetics and mechanism of the interconversion of inverse bicontinuous cubic
      mesophases.
AB  - This paper describes time-resolved x-ray diffraction data monitoring the
      transformation of one inverse bicontinuous cubic mesophase into another, in a
      hydrated lipid system. The first section of the paper describes a mechanism for
      the transformation that conserves the topology of the bilayer, based on the work
      of Charvolin and Sadoc, Fogden and Hyde, and Benedicto and O'Brien in this area.
      We show a pictorial representation of this mechanism, in terms of both the water
      channels and the lipid bilayer. The second section describes the experimental
      results obtained. The system under investigation was 2:1 lauric acid:
      dilauroylphosphatidylcholine at a hydration of 50% water by weight. A pressure
      jump was used to induce a phase transition from the gyroid (Q(G)(II)) to the
      diamond (Q(D)(II)) bicontinuous cubic mesophase, which was monitored by time
      resolved x-ray diffraction. The lattice parameter of both mesophases was found to
      decrease slightly throughout the transformation, but at the stage where the Q
      (D)(II) phase first appeared, the ratio of lattice parameters of the two phases
      was found to be approximately constant for all pressure-jump experiments. The
      value is consistent with a topology-preserving mechanism. However, the polydomain
      nature of our sample prevents us from confirming that the specific pathway is
      that described in the first section of the paper. Our data also reveal signals
      from two different intermediate structures, one of which we have identified as
      the inverse hexagonal (H(II)) mesophase. We suggest that it plays a role in the
      transfer of water during the transformation. The rate of the phase transition was
      found to increase with both temperature and pressure-jump amplitude, and its time
      scale varied from the order of seconds to minutes, depending on the conditions
      employed.

PMID- 16089966
TI  - Thermodynamic instabilities of a binary mixture of sticky hard spheres.
AB  - The thermodynamic instabilities of a binary mixture of sticky hard spheres (SHS)
      in the modified mean spherical approximation (mMSA) and the Percus-Yevick (PY)
      approximation are investigated using an approach devised by Chen and Forstmann
      [corrected] [J. Chem. Phys. [corrected] 97, 3696 (1992)]. This scheme hinges on a
      diagonalization of the matrix of second functional derivatives of the grand
      canonical potential with respect to the particle density fluctuations. The zeroes
      of the smallest eigenvalue and the direction of the relative eigenvector
      characterize the instability uniquely. We explicitly compute three different
      classes of examples. For a symmetrical binary mixture, analytical calculations,
      both for mMSA and for PY, predict that when the strength of adhesiveness between
      like particles is smaller than the one between unlike particles, only a pure
      condensation spinodal exists; in the opposite regime, a pure demixing spinodal
      appears at high densities. We then compare the mMSA and PY results for a mixture
      where like particles interact as hard spheres (HS) and unlike particles as SHS,
      and for a mixture of HS in a SHS fluid. In these cases, even though the mMSA and
      PY spinodals are quantitatively and qualitatively very different from each other,
      we prove that they have the same kind of instabilities. Finally, we study the
      mMSA solution for five different mixtures obtained by setting the stickiness
      parameters equal to five different functions of the hard sphere diameters. We
      find that four of the five mixtures exhibit very different type of instabilities.
      Our results are expected to provide a further step toward a more thoughtful
      application of SHS models to colloidal fluids.

PMID- 16089967
TI  - High-frequency microrheology of wormlike micelles.
AB  - We have measured the frequency-dependent shear modulus of entangled solutions of
      wormlike micelles by high-frequency microrheology and have compared the results
      with those from macrorheology experiments done on the same samples. Using optical
      microrheology based on laser interferometry we have measured loss and storage
      moduli over six decades in frequency up to about 100 kHz. We present data over a
      decade in concentration in the entangled regime and find good agreement between
      micro- and macrorheology, thus validating recently developed microrheology
      techniques. By collapsing data for different concentrations, we furthermore
      determine both the concentration scaling of the plateau modulus and a power-law
      exponent of the complex shear modulus at high frequencies.

PMID- 16089968
TI  - Electroconvective instability in concentration polarization and nonequilibrium
      electro-osmotic slip.
AB  - This paper concerns the comparison of electroconvective instability in
      concentration polarization at an ion-selective membrane with previously reported
      nonequilibrium electro-osmotic instability. Electro-osmotic formulation
      represents an asymptotic limit case of the electroconvective one. An improved
      nonequilibrium electro-osmotic slip formula is derived. Linear stability analysis
      for various nonequilibrium electro-osmotic formulations is carried out, including
      the analytic studies of the short- and long-wave limits. The obtained results are
      compared with those for a full electroconvective formulation. It is observed that
      the shortwave singularity typical for the nonequilibrium electro-osmotic
      instability is removed in the full electroconvective formulation. The effect of
      ionic diffusivities ratio on stability is discussed.

PMID- 16089969
TI  - Tunable generic model for fluid bilayer membranes.
AB  - We present a model for the efficient simulation of generic bilayer membranes.
      Individual lipids are represented by one head bead and two tail beads. By means
      of simple pair potentials these robustly self-assemble to a fluid bilayer state
      over a wide range of parameters, without the need for an explicit solvent. The
      model shows the expected elastic behavior on large length scales, and its
      physical properties (e.g., fluidity or bending stiffness) can be widely tuned via
      a single parameter. In particular, bending rigidities in the experimentally
      relevant range are obtained, at least within 3-30 k(B) T. The model is naturally
      suited to study many physical topics, including self-assembly, fusion, bilayer
      melting, lipid mixtures, rafts, and protein-bilayer interactions.

PMID- 16089970
TI  - Kinetics of phase separation in systems exhibiting simple coacervation.
AB  - The kinetics of phase separation of a homogeneous polyelectrolytic solution into
      a dense polymer-rich coacervate and the dilute supernatant phase is discussed
      through statistical thermodynamics. It has been shown that the coacervate phase
      is associated with higher internal pressure, consequently giving rise to
      syneresis. Physical conditions for phase separations has been deduced explicitly
      which reveals that sigma(2)/qrt[I] > or = constant (where sigma is
      polyelectrolyte charge density and I is solution ionic strength), consistent with
      experimental observations. In the lattice model, r is the number of sites
      occupied by the polymer having a volume critical fraction psi(2c), it was found
      that phase separation would ensue when sigma(3)r > or = (64/9 alpha(2))
      [psi(2c)/(1 - omega(2c))(2)], which reduces to (sigma(3)r/psi(2c)) > or = (64/9
      alpha(2)) approximately 0.45 at 20 degrees C for psi(2c) < 1. The separation
      kinetics mimics a spinodal decomposition process. Rate of release of supernatant
      due to syneresis was found to be independent of the initial coacervate mass.
      Syneresis results are discussed in the context of temporal evolution of self
      organization in polymer melts through Avrami model.

PMID- 16089971
TI  - Microscopic theory of glassy dynamics and glass transition for molecular
      crystals.
AB  - We derive a microscopic equation of motion for the dynamical orientational
      correlators of molecular crystals. Our approach is based upon mode coupling
      theory. Compared to liquids we find four main differences: (i) the memory kernel
      contains Umklapp processes if the total momentum of two orientational modes is
      outside the first Brillouin zone, (ii) besides the static two-molecule
      orientational correlators one also needs the static one-molecule orientational
      density as an input, where the latter is nontrivial due to the crystal's
      anisotropy, (iii) the static orientational current density correlator does
      contribute an anisotropic, inertia-independent part to the memory kernel, and
      (iv) if the molecules are assumed to be fixed on a rigid lattice, the tensorial
      orientational correlators and the memory kernel have vanishing l,l(') = 0
      components, due to the absence of translational motion. The resulting mode
      coupling equations are solved for hard ellipsoids of revolution on a rigid sc
      lattice. Using the static orientational correlators from Percus-Yevick theory we
      find an ideal glass transition generated due to precursors of orientational order
      which depend on X(0) and psi, the aspect ratio and packing fraction of the
      ellipsoids. The glass formation of oblate ellipsoids is enhanced compared to that
      for prolate ones. For oblate ellipsoids with X(0) < or = 0.7 and prolate
      ellipsoids with X(0) < or = 4, the critical diagonal nonergodicity parameters in
      reciprocal space exhibit more or less sharp maxima at the zone center with very
      small values elsewhere, while for prolate ellipsoids with 2 < or = X(0) < or =
      2.5 we have maxima at the zone edge. The off-diagonal nonergodicity parameters
      are not restricted to positive values and show similar behavior. For 0.7 < or =
      X(0) < or = 2, no glass transition is found because of too small static
      orientational correlators. In the glass phase, the nonergodicity parameters show
      a much more pronounced q dependence.

PMID- 16089972
TI  - X-ray specular reflectivity study of a critical binary fluid mixture.
AB  - We have used direct inversion of x-ray reflectivity data to extract the liquid
      vapor interface composition profile and the related critical scaling function of
      a binary mixture of dodecane and tetrabromoethane. The mixture was in the one
      phase region above its critical point. The results indicate the formation of a
      monolayer of the lower surface tension component followed by an abrupt change to
      a mixed composition which gradually relaxes to the bulk composition deep within
      the fluid.

PMID- 16089973
TI  - Double dendrite growth in solidification.
AB  - We present experiments on the doublon growth morphology in directional
      solidification. Samples used are succinonitrile with small amounts of
      poly(ethylene oxide), acetone, or camphor as the solute. Doublons, or symmetry
      broken dendrites, are generic diffusion-limited growth structures expected at
      large undercooling and low anisotropy. Low anisotropy growth is achieved by
      selecting a grain near the {111} plane leading to either seaweed (dense branching
      morphology) or doublon growth depending on experimental parameters. We find
      selection of doublons to be strongly dependent on solute concentration and sample
      orientation. Doublons are selected at low concentrations (low solutal
      undercooling) in contrast to the prediction of doublons at large thermal
      undercooling in pure materials. Doublons also exhibit preferred growth directions
      and changing the orientation of a specific doublonic grain changes the character
      and stability of the doublons. We observe transitions between seaweed and doublon
      growth with changes in concentration and sample orientation.

PMID- 16089974
TI  - Quantitative phase-field modeling of two-phase growth.
AB  - A phase-field model that allows for quantitative simulations of low-speed
      eutectic and peritectic solidification under typical experimental conditions is
      developed. Its cornerstone is a smooth free-energy functional, specifically
      designed so that the stable solutions that connect any two phases are completely
      free of the third phase. For the simplest choice for this functional, the
      equations of motion for each of the two solid-liquid interfaces can be mapped to
      the standard phase-field model of single-phase solidification with its quartic
      double-well potential. By applying the thin-interface asymptotics and by
      extending the antitrapping current previously developed for this model, all
      spurious corrections to the dynamics of the solid-liquid interfaces linear in the
      interface thickness W can be eliminated. This means that, for small enough values
      of W, simulation results become independent of it. As a consequence, accurate
      results can be obtained using values of W much larger than the physical interface
      thickness, which yields a tremendous gain in computational power and makes
      simulations for realistic experimental parameters feasible. Convergence of the
      simulation outcome with decreasing W is explicitly demonstrated. Furthermore, the
      results are compared to a boundary-integral formulation of the corresponding free
      boundary problem. Excellent agreement is found, except in the immediate vicinity
      of bifurcation points, a very sensitive situation where noticeable differences
      arise. These differences reveal that, in contrast to the standard assumptions of
      the free-boundary problem, out of equilibrium the diffuse trijunction region of
      the phase-field model can (i) slightly deviate from Young's law for the contact
      angles, and (ii) advance in a direction that forms a finite angle with the solid
      solid interface at each instant. While the deviation (i) extrapolates to zero in
      the limit of vanishing interface thickness, the small angle in (ii) remains
      roughly constant, which indicates that it might be a genuine physical effect,
      present even for an atomic-scale interface thickness.

PMID- 16089975
TI  - Influence of inhomogeneous substrate curvature on line tension.
AB  - Line tension accompanying equilibrium liquidlike films adsorbed at cylinder
      shaped substrates equipped with chemical heterogeneities is studied within an
      effective interfacial Hamiltonian approach. The heterogeneity has the form of a
      stripe of width 2L. The leading corrections to the line tension coefficient due
      to nonzero substrate curvature R(-1) are derived. Their character is shown to be
      sensitively dependent on the system's temperature regime. For temperatures low
      enough that both the homogeneous components of the heterogeneous substrate remain
      nonwetted, the leading curvature correction is found to be proportional to R(-1).
      For temperatures such that one of the solid surface components is wetted by the
      fluid, one obtains corrections to the line tension of the order of either (L/R)
      ln R or R(-1/2) depending on the relative values of R and the heterogeneity width
      2L . For temperatures exceeding wetting temperatures of both the substrate
      components, the line tension is shown to decay to 0 in the limit R --> infinity
      according to the power law eta approximately R(-1/2).

PMID- 16089976
TI  - Influence of pulsed laser heating on morphological relaxation of surface ripples.
AB  - A continuum (Mullins-type) model is proposed for the nonisothermal, isotropic
      evolution of a crystal surface on which mass transport occurs by surface
      diffusion. The departure from constant temperature is assumed induced by incident
      pulsed radiation. It has been shown experimentally and theoretically [see, e.g.,
      Yakunkin, High Temp. 26, 585 (1988); Yilbas and Kalyon, J. Phys. D. 34, 222
      (2001)] that such a heating mode gives rise to the quasistationary regime, in
      which the surface temperature of a thick solid film oscillates about the mean
      value with the pulse repetition frequency. The implications of oscillatory
      driving with high frequency values on relaxation of surface ripples are examined;
      in particular, the traveling wave solutions with decreasing amplitude are
      detected numerically. Pulsed heating also results in faster smoothing of the
      ripple, compared to the case when the surface is at constant temperature which is
      same as the mean temperature in the pulsed heating mode. Impact on ripple shape
      is minor for ripple amplitudes considered.

PMID- 16089977
TI  - Growth and form of spherulites.
AB  - Many structural materials (metal alloys, polymers, minerals, etc.) are formed by
      quenching liquids into crystalline solids. This highly nonequilibrium process
      often leads to polycrystalline growth patterns that are broadly termed
      "spherulites" because of their large-scale average spherical shape. Despite the
      prevalence and practical importance of spherulite formation, only rather
      qualitative concepts of this phenomenon exist. It is established that phase field
      methods naturally account for diffusional instabilities that are responsible for
      dendritic single-crystal growth. However, a generalization of this model is
      required to describe spherulitic growth patterns, and in the present paper we
      propose a minimal model of this fundamental crystal growth process. Our
      calculations indicate that the diversity of spherulitic growth morphologies
      arises from a competition between the ordering effect of discrete local
      crystallographic symmetries and the randomization of the local crystallographic
      orientation that accompanies crystal grain nucleation at the growth front [growth
      front nucleation (GFN)]. This randomization in the orientation accounts for the
      isotropy of spherulitic growth at large length scales and long times. In
      practice, many mechanisms can give rise to GFN, and the present work describes
      and explores three physically prevalent sources of disorder that lead to this
      kind of growth. While previous phase field modeling elucidated two of these
      mechanisms--disorder created by particulate impurities or other static disorder
      or by the dynamic heterogeneities that spontaneously form in supercooled liquids
      (even pure ones)--the present paper considers an additional mechanism,
      crystalline branching induced by a misorientation-dependent grain boundary
      energy, which can significantly affect spherulite morphology. We find the entire
      range of observed spherulite morphologies can be reproduced by this generalized
      phase field model of polycrystalline growth.

PMID- 16089978
TI  - Quasistatic relaxation of arbitrarily shaped sessile drops.
AB  - We study a spontaneous relaxation dynamics of arbitrarily shaped liquid drops on
      solid surfaces in the partial wetting regime. It is assumed that the energy
      dissipated near the contact line is much larger than that in the bulk of the
      fluid. We have shown rigorously in the case of quasi-static relaxation using the
      standard mechanical description of dissipative system dynamics that the
      introduction of a dissipation term proportional to the contact line length leads
      to the well-known local relation between the contact line velocity and the
      dynamic contact angle at every point of an arbitrary contact line shape. A
      numerical code is developed for three-dimensional drops to study the dependence
      of the relaxation dynamics on the initial drop shape. The available asymptotic
      solutions are tested against the obtained numerical data. We show how the
      relaxation at a given point of the contact line is influenced by the dynamics of
      the whole drop which is a manifestation of the nonlocal character of the contact
      line relaxation.

PMID- 16089979
TI  - Master-equation approach to the study of phase-change processes in data storage
      media.
AB  - We study the dynamics of crystallization in phase-change materials using a master
      equation approach in which the state of the crystallizing material is described
      by a cluster size distribution function. A model is developed using the
      thermodynamics of the processes involved and representing the clusters of size
      two and greater as a continuum but clusters of size one (monomers) as a separate
      equation. We present some partial analytical results for the isothermal case and
      for large cluster sizes, but principally we use numerical simulations to
      investigate the model. We obtain results that are in good agreement with
      experimental data and the model appears to be useful for the fast simulation of
      reading and writing processes in phase-change optical and electrical memories.

PMID- 16089980
TI  - Dynamic scaling form in wavelet-discriminated Edwards-Wilkinson growth equation.
AB  - We present an analysis of dynamic scaling of the Edwards-Wilkinson growth model
      from wavelets' perspective. Scaling function for the surface width is determined
      using wavelets' formalism, by computing the surface width for each wavelet scale,
      we show that an exact and simple form of the scaling function is obtained. These
      predictions are confirmed by computer simulation of a growth model described by
      the EW equation, and by numerical calculations.

PMID- 16089981
TI  - Phase behavior of a nematic liquid crystal in contact with a chemically and
      geometrically structured substrate.
AB  - A nematic liquid crystal in contact with a grating surface possessing an
      alternating stripe pattern of locally homeotropic and planar anchoring is studied
      within the Frank-Oseen model. The combination of both chemical and geometrical
      surface pattern leads to rich phase diagrams, involving a homeotropic, a planar,
      and a tilted nematic texture. The effect of the groove depth and the anchoring
      strengths on the location and the order of phase transitions between different
      nematic textures is studied. A zenithally bistable nematic device is investigated
      by confining a nematic liquid crystal between the patterned grating surface and a
      flat substrate with strong homeotropic anchoring.

PMID- 16089982
TI  - Visible and near-infrared characterization and modeling of nanosized holographic
      polymer-dispersed liquid crystal gratings.
AB  - We have studied the electro-optical and angular behavior of holographic-polymer
      dispersed liquid crystal gratings at different wavelengths, in the visible and in
      the near-infrared range. As usual in these kinds of materials, a strong
      polarization dependent behavior was observed. Our samples showed very high
      diffraction efficiency for p-polarized radiation at 1.55 microm, which is very
      interesting for many possible applications in the telecom field. However, we also
      observed a very unusual behavior for visible p-polarized light and we try to
      suggest some explanation for that. By analyzing the angular dependence of the
      diffraction efficiency, we could measure the components of the permittivity
      modulation tensor and infer important information about the main parameters
      involved in the grating structure: the degree of phase separation and the
      anisotropy in the liquid crystal droplet distribution. In our opinion, this
      simple and nondestructive methodology can be very useful for studying these kinds
      of materials and getting information on their morphology, in view of optimizing
      their properties. Finally, we discuss the role of the refractive index optical
      dispersion in order to describe the behavior of these materials at different
      wavelengths. These remarks are especially important when properties in the
      infrared range are extrapolated from measurements in the visible.

PMID- 16089983
TI  - Soft elasticity in smectic elastomers.
AB  - We investigate the soft elastic modes of smectic elastomers, that is shape change
      without energy cost. We use a microscopic model for their nonlinear elasticity,
      similar to those used for nematic elastomers. We consider two different phases of
      smectic elastomer; the biaxial smectic A for a simple illustration, and smectic C
      phases which are of great practical significance. We show that only one
      nontrivial trajectory of the director gives soft deformations. We give a
      geometrical interpretation of this soft elastic mode and give an explicit
      example.

PMID- 16089984
TI  - Dynamics of fluctuations in smectic membranes.
AB  - We present a comprehensive account of the dynamics of layer-displacement
      fluctuations in smectic liquid-crystal membranes as studied by x-ray photon
      correlation spectroscopy (XPCS) and neutron-spin echo (NSE). Combining these two
      techniques at fast relaxation times, three distinct relaxation regimes can be
      distinguished. For thin membranes, at the specular Bragg position oscillatory
      relaxation occurs, which transforms for thicker samples into exponential decay.
      Above a critical off-specular angle, in XPCS exponential relaxation is observed
      that does not depend on the scattering angle. This indicates relaxation times
      that are independent of the wavelength of the fluctuations. In this regime the
      relaxation of the fluctuations is dominated by the surface tension. Using NSE
      larger off-specular angles can be reached than by XPCS, for which the relaxation
      time decreases with the scattering angle. This regime is dominated by the bulk
      elasticity of the smectic membrane. The results are compared with theoretical
      models for the fluctuation behavior of smectic membranes, in which effects of the
      mosaic distribution and of the center of mass movement of the smectic membranes
      must be incorporated.

PMID- 16089985
TI  - Buckling instability of droplet chains in freely suspended smectic films.
AB  - A buckling instability of chains of isotropic droplets in smectic films is
      investigated. The c -director field in a free-standing film is prepared as a
      target pattern with a continuous radial deformation. In such a pattern, isotropic
      liquid droplets are induced by light irradiation of the photochromic mesogenic
      material. The droplets align tangentially in regular chains in the regular
      structure of the c -director field. Incorporation of additional droplets
      lengthens the chains at a given ring diameter until they form complete rings.
      Further chain growth introduces a reversible buckling with a characteristic wave
      length. The phenomenon is similar in many respects to growth processes in
      biosystems or Euler buckling in polymer foils. A simple model of the wavelength
      selection mechanism is introduced.

PMID- 16089986
TI  - Mechanics of soft-solid-liquid-crystal interfaces.
AB  - The interfacial mechanics of soft elastic solids and nematic liquid crystals is
      presented. The theory can be applied to interfaces involving gels, elastomers,
      biomaterials, and thermotropic nematic liquid crystals. A model of anisotropic
      elastic interfaces is formulated and used to derive two fundamental capillary
      quantities: (i) interfacial torques on the nematic orientation, and (ii)
      capillary pressure. The couplings between soft-solid deformation and liquid
      crystal anisotropic interfacial tension is shown to lead to strain-induced
      anchoring transitions, and strain-induced morphological instabilities.

PMID- 16089987
TI  - Experimental investigation of equibiaxial extension and breakup of drops in a
      molten two-phase polymer blend.
AB  - We experimentally investigate the breakup of an equibiaxially elongated
      polystyrene (PS) drop in a poly(methyl methacrylate) (PMMA) matrix during
      relaxation after melt elongation. In equibiaxial elongation, the initially
      spherical PS drop is deformed into an ellipsoidal disclike shape for our test
      parameters. Using a hotstage in combination with a light microscope, we observe
      the evolution of the drop shape during relaxation. In the initial stage of
      relaxation, fingers and holes are formed. The holes are located preferentially
      near the rim of the drop. The number and the size of the holes increase with time
      such that the elongated PS drop attains a complex shape during relaxation. The
      fingers form bulbous ends which separate from the fingers. We discuss the
      dynamics of this breakup process by taking into account the interfacial energy
      between PS and PMMA. Our analysis shows that a very large number of small PS
      droplets can be generated by the sequential breakup of the elongated PS drop.

PMID- 16089988
TI  - Pressure-enhanced dynamic heterogeneity in block copolymers of poly(methyl vinyl
      ether) and poly(isobutyl vinyl ether).
AB  - The static structure factor and associated dynamics have been investigated in a
      series of block copolymers of poly(methyl vinyl ether) (PMVE) and poly(isobutyl
      vinyl ether) (PiBVE) using x-ray scattering and dielectric spectroscopy (DS). The
      origin of the dynamic arrest at the glass temperature (T(g)) of PiBVE has been
      explored by temperature- and pressure-dependent DS and pressure-volume
      temperature measurements. Both temperature and volume are responsible for the
      segmental dynamics but temperature has a stronger effect. The copolymers display
      a minimal dynamic asymmetry (Delta T(g) approximately 7 K), nevertheless, are
      spatially and dynamically heterogeneous. Increasing pressure, unlike temperature,
      enhances the dynamic heterogeneity. This effect originates from the distinctly
      different pressure sensitivities of the homopolymers and can be traced back to
      differences in local packing.

PMID- 16089989
TI  - Assembly of one-dimensional supramolecular objects: from monomers to networks.
AB  - One-dimensional supramolecular aggregates can form networks at exceedingly low
      concentrations. Recent experiments in several laboratories, including our own,
      have demonstrated the formation of gels by these systems at concentrations well
      under 1% by weight. The systems of interest in our laboratory form either
      cylindrical nanofibers or ribbons as a result of strong noncovalent interactions
      among monomers. The stiffness and interaction energies among these thread-like
      objects can vary significantly depending on the chemical structure of the
      monomers used. We have used Monte Carlo simulations to study the structure of the
      threads and their ability to form networks through bundle formation. The
      persistence length of the threads was found to be strongly affected not only by
      stiffness, but also by the strength of attractive two-body interactions among
      thread segments. The relative values of stiffness and attractive two-body
      interaction strength determine if threads collapse or create bundles. Only in the
      presence of sufficiently long threads and bundle formation can these systems
      assemble into networks of high connectivity.

PMID- 16089990
TI  - Phase-field modeling on morphological landscape of isotactic polystyrene single
      crystals.
AB  - Spatio-temporal growth of isotactic polystyrene single crystals during isothermal
      crystallization has been investigated theoretically based on the phase field
      model by solving temporal evolution of a nonconserved phase order parameter
      coupled with a heat conduction equation. In the description of the total free
      energy, an asymmetric double-well local free energy density has been adopted to
      represent the metastable melt and the stable solid crystal. Unlike the small
      molecule systems, polymer crystallization rarely reaches thermodynamic
      equilibrium; most polymer crystals are kinetically stabilized in some metastable
      states. To capture various metastable polymer crystals, the phase field crystal
      order parameter at the solidification potential has been treated to be
      supercooling dependent such that it can assume an intermediate value between zero
      (melt) and unity (perfect crystal), reflecting imperfect polycrystalline nature
      of polymer crystals. Two-dimensional simulations exhibit various single crystal
      morphologies of isotactic polystyrene crystals such as faceted hexagonal patterns
      transforming to nonfaceted snowflakes with increasing supercooling. Of particular
      interest is that heat liberation from the crystallizing front influences the
      curvature of the crystal-melt interface, leading to directional growth of
      lamellar tips and side branches. The landscape of these morphological textures
      has been established as a function of anisotropy of surface energy and
      supercooling. With increasing supercooling and decreasing anisotropy, the
      hexagonal single crystal transforms to the dense lamellar branching morphology in
      conformity with the experimental findings.

PMID- 16089991
TI  - Orientational ordering and dynamics of rodlike polyelectrolytes.
AB  - The interplay between electrostatic interactions and orientational correlations
      is studied for a model system of charged rods positioned on a chain, using Monte
      Carlo simulation techniques. It is shown that the coupling brings about the
      notion of electrostatic frustration, which in turn results in: (i) a rich variety
      of orientational orderings such as chiral phases, and (ii) an inherently slow
      dynamics characterized by stretched-exponential behavior in the relaxation
      functions of the system.

PMID- 16089992
TI  - Correlated disorder in random block copolymers.
AB  - We study the effect of a random Flory-Huggins parameter in a symmetric diblock
      copolymer melt which is expected to occur in a copolymer where one block is near
      its structural glass transition. In the clean limit the microphase segregation
      between the two blocks causes a weak, fluctuation induced first order transition
      to a lamellar state. Using a renormalization group approach combined with the
      replica trick to treat the quenched disorder, we show that beyond a critical
      disorder strength, which depends on the length of the polymer chain, the
      character of the transition is changed. The system becomes dominated by strong
      randomness and a glassy rather than an ordered lamellar state occurs. A
      renormalization of the effective disorder distribution leads to nonlocal disorder
      correlations that reflect strong compositional fluctuation on the scale of the
      radius of gyration of the polymer chains. The reason for this behavior is shown
      to be the chain length dependent role of critical fluctuations, which are less
      important for shorter chains and become increasingly more relevant as the polymer
      length increases and the clean first order transition becomes weaker.

PMID- 16089993
TI  - Creating structures in polymer blends via a dissolution and phase-separation
      process.
AB  - We show how three-dimensional structures can be formed in polymer blends from pre
      existing structures. "Tape" of one polymer is inserted into a matrix of an
      alternative polymer to form an array of parallelepipeds. We subject this regular
      structure to partial dissolution in the one-phase region, before quenching the
      system into the two-phase region. The interplay between dissolution and phase
      separation can result in complex hierarchic structures. In particular, arrays of
      microchannels of one polymer species can be formed inside the other polymer.

PMID- 16089994
TI  - Scaling theory of polyelectrolyte adsorption on a repulsive charged surface.
AB  - We studied the problem of many-polyelectrolyte adsorption on a repulsive charged
      surface by scaling analysis. According to ratio of the dielectric constant
      between the medium and the substrate, the phase diagrams of the adsorbed layer
      are divided into two classes. Their phase diagrams are qualitatively different.
      The polyelectrolytes of low (high) f Z2 are adsorbed for low (high) dielectric
      ratio, where f is the fraction of charged monomers and Z is the polyelectrolyte
      valency.

PMID- 16089995
TI  - Dynamics of fluid vesicles in shear flow: effect of membrane viscosity and
      thermal fluctuations.
AB  - The dynamical behavior of vesicles is investigated in simple shear flow. A
      simulation technique is presented that combines a three-dimensional particle
      based mesoscopic model (multiparticle collision dynamics) for the solvent with a
      dynamically triangulated surface model for the membrane. In this model, thermal
      fluctuations of the solvent and of the membrane are consistently taken into
      account. The membrane viscosity can be varied by changing the bond-flip rate of
      the dynamically triangulated surface. Vesicles are found to transit from steady
      tank-treading to unsteady tumbling motion with increasing membrane viscosity. At
      small reduced volumes, the shear induces a transformation from a discocyte to a
      prolate shape at low membrane viscosity. On the other hand, at high membrane
      viscosity, the shear induces a transformation from prolate to discocyte, or
      tumbling motion accompanied by shape oscillations between these two states.
      Thermal fluctuations induce intermittent tumbling and smooth out the transitions.
      This effect can be understood from a simplified stochastic model.

PMID- 16089996
TI  - Noise correlation length effects on a Morris-Lecar neural network.
AB  - The role of spatially correlated stochastic perturbations on a Morris-Lecar
      neural network subject to an aperiodic subthreshold signal is analyzed in detail.
      Our results suggest that optimum signal-to-noise ratios can be obtained for two
      critical noise intensities due to the interplay of the subthreshold Poisson
      process and the correlated Gaussian forcing. For the second peak, most of the
      cells are periodically excited, the information transfer is enhanced, and a
      collective behavior develops measured in terms of the averaged activity of the
      network. The maximum signal-to-noise ratio increases with the correlation length,
      although it saturates for global coupling. It was found that there is a range of
      mean frequencies of the subthreshold signal that increases the signal-to-noise
      ratio output.

PMID- 16089997
TI  - Budding and domain shape transformations in mixed lipid films and bilayer
      membranes.
AB  - We study the stability and shapes of domains with spontaneous curvature in fluid
      films and membranes, embedded in a surrounding membrane with zero spontaneous
      curvature. These domains can result from the inclusion of an impurity in a fluid
      membrane or from phase separation within the membrane. We show that for small but
      finite line and surface tensions and for finite spontaneous curvatures, an
      equilibrium phase of protruding circular domains is obtained at low impurity
      concentrations. At higher concentrations, we predict a transition from circular
      domains, or caplets, to stripes. In both cases, we calculate the shapes of these
      domains within the Monge representation for the membrane shape. With increasing
      line tension, we show numerically that there is a budding transformation from
      stable protruding circular domains to spherical buds. We calculate the full phase
      diagram and demonstrate two triple points of, respectively, bud-flat-caplet and
      flat-stripe-caplet coexistence.

PMID- 16089998
TI  - Propagator theory of brain dynamics.
AB  - A physiologically based continuum model of brain dynamics is extended to
      incorporate arbitrary numbers of structures and neural populations, multiple
      outgoing fields of activity from a single population of neurons to various
      targets, improved treatment of converging or diverging projections and mesoscopic
      structure, and generalized connections to quantities observable via
      electroencephalography and other methods. The results are applied to study the
      corticothalamic system, predicting an intracortical resonance that leads to
      enhancements of electroencephalographic activity in the gamma (>30 Hz) range.
      This resonance involves feedback loops incorporating slow, short-range inhibitory
      fibers.

PMID- 16089999
TI  - Asymptotic construction of pulses in the discrete Hodgkin-Huxley model for
      myelinated nerves.
AB  - A quantitative description of pulses and wave trains in the spatially discrete
      Hodgkin-Huxley model for myelinated nerves is given. Predictions of the shape and
      speed of the waves and the thresholds for propagation failure are obtained. Our
      asymptotic predictions agree quite well with numerical solutions of the model and
      describe wave patterns generated by repeated firing at a boundary.

PMID- 16090000
TI  - Perceptron learning of pairwise contact energies for proteins incorporating the
      amino acid environment.
AB  - Although a coarse-grained description of proteins is a simple and convenient way
      to attack the protein folding problem, the construction of a global pairwise
      energy function which can simultaneously recognize the native folds of many
      proteins has resulted in partial success. We have sought the possibility of a
      systematic improvement of this pairwise-contact energy function as we extended
      the parameter space of amino acids, incorporating local environments of amino
      acids, beyond a 20 x 20 matrix. We have studied the pairwise contact energy
      functions of 20 x 20, 60 x 60, and 180 x 180 matrices depending on the extent of
      parameter space, and compared their effect on the learnability of energy
      parameters in the context of a gapless threading, bearing in mind that a 20 x 20
      pairwise contact matrix has been shown to be too simple to recognize the native
      folds of many proteins. In this paper, we show that the construction of a global
      pairwise energy function was achieved using 1006 training proteins of a homology
      of less than 30%, which include all representatives of different protein classes.
      After parametrizing the local environments of the amino acids into nine
      categories depending on three secondary structures and three kinds of
      hydrophobicity (desolvation), the 16290 pairwise contact energies (scores) of the
      amino acids could be determined by perceptron learning and protein threading.
      These could simultaneously recognize all the native folds of the 1006 training
      proteins. When these energy parameters were tested on the 382 test proteins of a
      homology of less than 90%, 370 (96.9%) proteins could recognize their native
      folds. We set up a simple thermodynamic framework in the conformational space of
      decoys to calculate the unfolded fraction and the specific heat of real proteins.
      The different thermodynamic stabilities of E.coli ribonuclease H (RNase H) and
      its mutants were well described in our calculation, agreeing with the experiment.

PMID- 16090001
TI  - Dynamics of learning in coupled oscillators tutored with delayed reinforcements.
AB  - In this work we analyze the solutions of a simple system of coupled phase
      oscillators in which the connectivity is learned dynamically. The model is
      inspired by the process of learning of birdsongs by oscine birds. An oscillator
      acts as the generator of a basic rhythm and drives slave oscillators which are
      responsible for different motor actions. The driving signal arrives at each
      driven oscillator through two different pathways. One of them is a direct
      pathway. The other one is a reinforcement pathway, through which the signal
      arrives delayed. The coupling coefficients between the driving oscillator and the
      slave ones evolve in time following a Hebbian-like rule. We discuss the
      conditions under which a driven oscillator is capable of learning to lock to the
      driver. The resulting phase difference and connectivity are a function of the
      delay of the reinforcement. Around some specific delays, the system is capable of
      generating dramatic changes in the phase difference between the driver and the
      driven systems. We discuss the dynamical mechanism responsible for this effect
      and possible applications of this learning scheme.

PMID- 16090002
TI  - Model for the distributions of k-mers in DNA sequences.
AB  - The evolutionary features based on the distributions of k-mers in the DNA
      sequences of various organisms are studied. The organisms are classified into
      three groups based on their evolutionary periods: (a) E. coli and T. pallidum (b)
      yeast, zebrafish, A. thaliana, and fruit fly, (c) mouse, chicken, and human. The
      distributions of 6-mers of these three groups are shown to be, respectively, (a)
      unimodal, (b) unimodal with peaks generally shifted to smaller frequencies of
      occurrence, (c) bimodal. To describe the bimodal feature of the k-mer
      distributions of group (c), a model based on the cytosine-guanine " CG" content
      of the DNA sequences is introduced and shown to provide reasonably good
      agreements.

PMID- 16090003
TI  - Upper limits of dielectric permittivity modulation in bacteriorhodopsin films.
AB  - A theoretical study of light-induced modulation of the dielectric permittivity in
      bacteriorhodopsin films has been done (including B--> M and B --> Q transitions).
      Analysis of dielectric permittivity modulation enables us to determine the
      fundamental limits of BR to be used in a holographic data storage system,
      together with the optimum experimental and material conditions. In order to carry
      out this analysis, the macroscopic dielectric permittivity was related to the
      microscopic polarizability of the three states of BR considered (B, M and Q).
      This parameter was calculated using a modelization procedure that includes the
      effect of ASP85, TRP86, and TYR185 amino acid residues (the B3LYP/6-31+ G(*)
      method was used for the calculations). Good concordance between theoretical
      calculations and experimental data was found for the linear optical properties
      (absorption wavelength, transition dipole moment, and dielectric permittivity
      modulation). The theoretical upper limits of Deltaepsilson at 750 nm (far from
      the resonance of the molecule) in a randomly oriented material are about 0.01 and
      0.012 for B--> M and B--> Q transitions, respectively. The values of Deltaepsilon
      obtained were used to simulate diffraction efficiencies (eta) of a volume phase
      hologram recorded in a BR film. The high absorptive losses at low wavelengths
      (about 625 nm ) cause an interesting behavior, since the highest Deltaepsilom do
      not produce the greatest eta. The highest eta is produced for a hologram
      thickness in the range of 900-1000 microm and working wavelength of 700-750 nm.

PMID- 16090004
TI  - Dynamic simulations of membranes with cytoskeletal interactions.
AB  - We describe a simulation algorithm for the dynamics of elastic membrane sheets
      over long length and time scales. Our model includes implicit hydrodynamic
      coupling between membrane and surrounding solvent and allows for arbitrary
      external forces acting on the membrane surface. In particular, the methodology is
      well suited to studying membranes in interaction with cytoskeletal filaments. We
      present results for the thermal undulations of a lipid bilayer attached to a
      regular network of spectrin filaments as a model for the red blood cell membrane.
      The dynamic fluctuations of the bilayer over the spectrin network are quantified
      and used to predict the macroscopic diffusion constant of band 3 on the surface
      of the red blood cell. We find that thermal undulations likely play a role in the
      mobility of band 3 in the plane of the erythrocyte membrane.

PMID- 16090005
TI  - Steepest descent calculation of RNA pseudoknots.
AB  - We enumerate possible topologies of pseudoknots in single-stranded RNA molecules.
      We use a steepest-descent approximation in the large N matrix field theory, and a
      Feynman diagram formalism to describe the resulting pseudoknot structure.

PMID- 16090006
TI  - Phase transitions in multiplicative competitive processes.
AB  - We introduce a discrete multiplicative process as a generic model of competition.
      Players with different abilities successively join the game and compete for
      finite resources. Emergence of dominant players and evolutionary development
      occur as a phase transition. The competitive dynamics underlying this transition
      is understood from a formal analogy to statistical mechanics. The theory is
      applicable to bacterial competition, predicting novel population dynamics near
      criticality.

PMID- 16090007
TI  - Volatility of linear and nonlinear time series.
AB  - Previous studies indicated that nonlinear properties of Gaussian distributed time
      series with long-range correlations, u(i), can be detected and quantified by
      studying the correlations in the magnitude series |u(i)|, the "volatility."
      However, the origin for this empirical observation still remains unclear and the
      exact relation between the correlations in u(i) and the correlations in |u(i)| is
      still unknown. Here we develop analytical relations between the scaling exponent
      of linear series u(i) and its magnitude series |u(i)|. Moreover, we find that
      nonlinear time series exhibit stronger (or the same) correlations in the
      magnitude time series compared with linear time series with the same two-point
      correlations. Based on these results we propose a simple model that generates
      multifractal time series by explicitly inserting long range correlations in the
      magnitude series; the nonlinear multifractal time series is generated by
      multiplying a long-range correlated time series (that represents the magnitude
      series) with uncorrelated time series [that represents the sign series sgn
      (u(i))]. We apply our techniques on daily deep ocean temperature records from the
      equatorial Pacific, the region of the El-Nino phenomenon, and find: (i) long
      range correlations from several days to several years with 1/f power spectrum,
      (ii) significant nonlinear behavior as expressed by long-range correlations of
      the volatility series, and (iii) broad multifractal spectrum.

PMID- 16090008
TI  - Computer simulations of sympatric speciation in a simple food web.
AB  - Galapagos finches, have motivated much theoretical research aimed at
      understanding the processes associated with the formation of the species.
      Inspired by them, in this paper we investigate the process of sympatric
      speciation in a simple food web model. For that we modify the individual-based
      Penna model that has been widely used to study aging as well as other
      evolutionary processes. Initially, our web consists of a primary food source and
      a single herbivore species that feeds on this resource. Subsequently we introduce
      a predator that feeds on the herbivore. In both instances we manipulate directly
      a basal resource distribution and monitor the changes in the populations.
      Sympatric speciation is obtained for the top species in both cases, and our
      results suggest that the speciation velocity depends on how far up, in the food
      chain, the focus population is feeding. Simulations are done with three different
      sexual imprinting-like mechanisms, in order to discuss adaptation by natural
      selection.

PMID- 16090009
TI  - Flexible lipid bilayers in implicit solvent.
AB  - A minimalist simulation model for lipid bilayers is presented. Each lipid is
      represented by a flexible chain of beads in implicit solvent. The hydrophobic
      effect is mimicked through an intermolecular pair potential localized at the
      "water"/hydrocarbon tail interface. This potential guarantees realistic
      interfacial tensions for lipids in a bilayer geometry. Lipids self-assemble into
      bilayer structures that display fluidity and elastic properties consistent with
      experimental model membrane systems. Varying molecular flexibility allows for
      tuning of elastic moduli and area per molecule over a range of values seen in
      experimental systems.

PMID- 16090010
TI  - Structure optimization by conformational space annealing in an off-lattice
      protein model.
AB  - The optimization results by conformational space annealing are presented for an
      off-lattice protein model consisting of hydrophobic and hydrophilic residues in
      Fibonacci sequences. The ground-state energies found are lower than those
      reported in the literature. In addition, the ground-state conformations in three
      dimensions exhibit the important aspect of forming a single hydrophobic core in
      real proteins. The energy landscape for the population of local minima is also
      investigated.

PMID- 16090011
TI  - Interplay between chemical reactions and transport in structured spaces.
AB  - The main motivation behind this study is to understand the interplay between the
      reactions and transport in a geometries that are not compact. Typical examples of
      compact geometries are a box or a sphere. A network made of containers C(1) ,
      C(2),..., C(N) and tubes is an example of the space that is structured and
      noncompact. In containers, particles react with the rate lambda. Tubes connecting
      containers allow for the exchange of chemicals with the transport rate D. A
      situation is considered where a number of reactants is small and kinetics is
      noise dominated. A method is presented that can be used to calculate the average
      and higher moments of the reaction time. A number of different chemical reactions
      are studied and their performance compared in various ways. Two schemes are
      discussed in general, the reaction on a fixed geometry ensemble (ROGE) and the
      geometry on a fixed reaction ensemble, examples are given in the ROGE case. The
      most important findings are as follows. (i) There is a large number of reactions
      that run faster in a networklike geometry. Such reactions contain antagonistic
      catalytic influences in the intermediate stages of a reaction scheme that are
      best dealt with in a networklike structure. (ii) Antagonistic catalytic
      influences are hard to identify since they are strongly connected to the pattern
      of injected molecules (inject pattern) and depend on the choice of molecules that
      have to be synthesized at the end (task pattern). (iii) The reaction time depends
      strongly on the details of the inject and task patterns.

PMID- 16090012
TI  - Scaling in force spectroscopy of macromolecules.
AB  - We use molecular dynamics to determine the force needed to rupture a chain
      molecule being stretched at constant loading rate and temperature. When all
      energy bonds of the molecule are identical, we find that the force F depends on
      the pulling rate r and temperature T according to F approximately const-
      T(1/3)|ln (r/T)|(1/3). When a single weak bond is introduced, this result is
      modified to F approximately const - T(2/3|ln (r/T)(2/3)|. This scaling, which is
      model independent, can be used with experiment to quantitatively extract relevant
      microscopic parameters.

PMID- 16090014
TI  - Thermodynamic pressure of a fluid confined in a random porous medium.
AB  - Up to now, none of the previously derived expressions is usable in simulations
      for the practical calculation of the thermodynamic pressure of a fluid adsorbed
      in a random porous medium. A bona fide virial expression of this pressure is
      presented. Contrary to what was believed, we show that this pressure is a
      measurable quantity and propose an experimental procedure for its measurement.

PMID- 16090013
TI  - Nonlinear software sensor for monitoring genetic regulation processes with noise
      and modeling errors.
AB  - Nonlinear control techniques by means of a software sensor that are commonly used
      in chemical engineering could be also applied to genetic regulation processes. We
      provide here a realistic formulation of this procedure by introducing an additive
      white Gaussian noise, which is usually found in experimental data. Besides, we
      include model errors, meaning that we assume we do not know the nonlinear
      regulation function of the process. In order to illustrate this procedure, we
      employ the Goodwin dynamics of the concentrations [B. C. Goodwin, (Academic, New
      York, 1963)] in the simple form recently applied to single gene systems and some
      operon cases [H. De Jong, J. Comput. Biol. 9, 67 (2002)], which involves the
      dynamics of the mRNA, given protein and metabolite concentrations. Further, we
      present results for a three gene case in coregulated sets of transcription units
      as they occur in prokaryotes. However, instead of considering their full
      dynamics, we use only the data of the metabolites and a designed software sensor.
      We also show, more generally, that it is possible to rebuild the complete set of
      nonmeasured concentrations despite the uncertainties in the regulation function
      or, even more, in the case of not knowing the mRNA dynamics. In addition, the
      rebuilding of concentrations is not affected by the perturbation due to the
      additive white Gaussian noise and also we managed to filter the noisy output of
      the biological system.

PMID- 16090015
TI  - Analogy of the slow dynamics between the supercooled liquid and supercooled
      plastic crystal states of difluorotetrachloroethane.
AB  - Slow dynamics of difluorotetrachloroethane in both supercooled plastic crystal
      and supercooled liquid states have been investigated with molecular dynamics
      simulations. The temperature and wave-vector dependence of collective dynamics in
      both states are probed using coherent dynamical scattering functions S (Q,t). Our
      results confirm the strong analogy between molecular liquids and plastic crystals
      for which alpha-relaxation times and nonergodicity parameters are controlled by
      the nontrivial static correlations S (Q), as predicted by the mode coupling
      theory.

PMID- 16090016
TI  - Roughness of two-dimensional surfaces with global constraints.
AB  - We study dynamical scaling properties of the two-dimensional surface growth
      models with global constraints. These include the growth model from a partition
      function Z = sigma{(h(r)Pi(h = h)(min) (h(max)) 1/2 (1 + z (n(h))), multiparticle
      correlated surface growth models and dissociative Q-mer growth models. The
      equilibrium surfaces of all the models except the dimer model show the same
      dynamical scaling behavior W2 (L,t) = (1/2piK(G)) ln [L g (t/L(z(W)))] with z(W)
      = 2.5 and K(G) = 0.916 , whereas the surface in the dimer model has a correction
      to the scaling. The growing (eroding) surfaces have two phases. The models with z
      > or = 0 show the normal Kardar-Parisi-Zhang scaling behavior. In contrast the
      models with -1 < or = z < 0 and multiparticle-correlated growth model manifest
      grooved surface structures with alpha = 1. The growing surfaces of Q -mer models
      form rather complex facets.

PMID- 16090017
TI  - Dissolution dynamics of NaCl nanocrystal in liquid water.
AB  - The dissolution dynamics of a NaCl nanocrystal in liquid water was studied using
      molecular dynamics simulations. The dissolution process was found to start with a
      Cl(-) ion at a corner site, followed by a Na(+) ion nearby. Both show directional
      preference in the dissolution path. An ion sequence with alternating charge,
      i.e., Cl(-), Na(+), Cl(-), Na(+), etc. was found to dominate the dissolution
      process. This image can be understood from the ionic hydration structures and the
      Coulomb interaction between the ions.

PMID- 16090018
TI  - Scaling, genetic drift, and clonal interference in the extinction pattern of
      asexual population.
AB  - We investigate the dynamics of loss of favorable mutations in an asexual haploid
      population. In the current work, we consider homogeneous as well as spatially
      structured population models. We focus our analysis on statistical measurements
      of the probability distribution of the maximum population size N(sb) achieved by
      those mutations that have not reached fixation. Our results show a crossover
      behavior which demonstrates the occurrence of two evolutionary regimes. In the
      first regime, which takes place for small N(sb) , the probability distribution is
      described by a power law with characteristic exponent theta(d) =1.8 +/- 0.01.
      This power law is not influenced by the rate of beneficial mutations. The second
      regime, which occurs for intermediate to large values of N(sb), has a
      characteristic exponent theta(c) which increases as the rate of beneficial
      mutations grows. These results establish where genetic drift and clonal
      interference become the main underlying mechanism in the extinction of
      advantageous mutations.

PMID- 16090019
TI  - Light-noise-induced suprathreshold circadian oscillations and coherent resonance
      in Drosophila.
AB  - Based on a reduced circadian oscillator model in Drosophila [Smolen, Biophys. J.
      83, 2349 (2002)], the effects of light noise and time delay on a circadian
      oscillator near a Hopf bifurcation are studied by using numerical computation.
      When the light-controlled parameter is suprathreshold, it was found that the
      circadian oscillations can be induced by light fluctuation. There is an optimal
      light noise intensity at which a remarkable coherent circadian oscillation is
      observed, which implies a significant resonance phenomenon in the sense of
      preferred biological circadian oscillations. Time delay can control the coherence
      of noise-induced circadian oscillations and the strength of coherent resonance
      achieves a maximum under a moderate time delay.

PMID- 16090020
TI  - Raman, hyper-Raman, hyper-Rayleigh, two-photon luminescence and morphology
      dependent resonance modes in a single optical tweezers system.
AB  - We present a setup of optical tweezers combined with linear and nonlinear
      microspectroscopies that enhances the capabilities of capture and analysis of
      both techniques. We can use either a continuous-wave (cw) Ti:sapphire laser for
      Raman measurements or a pulsed femtosecond Ti:sapphire laser that permitted the
      observation of nonlinear results such as hyper-Raman, hyper-Rayleigh, and two
      photon luminescence. Only the high peak intensity of the femtosecond laser allows
      the observation of all these nonlinear spectroscopies. The sensitivity of our
      system also permitted the observation of morphology-dependent resonance (MDR)
      modes of a single stained trapped microsphere of 6 microm. The possibility of
      performing spectroscopy in a living microorganism optically trapped in any
      desired neighborhood would mean that one can dynamically observe the chemical
      reactions and/or mechanical properties changing in real time.

PMID- 16090021
TI  - Comment on "numerical investigation of optically induced director oscillations in
      nematic liquid crystals.".
AB  - A nonlinear optical system based on nematic liquid crystals film was numerically
      investigated by Demeter and Kramer in [Phys. Rev. E 64, 020701(R) (2001)]. They
      show that the uncommon route to chaos via a cascade of homoclinic gluing
      bifurcations predicted by a perturbative approach surprinsingly does not exist
      when the problem is solved exactly. On the other hand, the system still exhibits
      a secondary instability but its threshold is found to be much higher than
      previously reported. We clarify the reason for the failure of the perturbative
      approach and its limits of applicability. Moreover, the significant increase of
      the secondary instability threshold can be understood from a nonrealistic
      amplification of light intensity introduced by the perturbative model.

PMID- 16090022
TI  - Comment on "local elastic stability for nematic liquid crystals".
AB  - We discuss a theory recently proposed by Virga and co-workers for the analysis of
      the local elastic stability of nematic liquid crystals [R. Rosso, E. G. Virga,
      and S. Kralj, Phys. Rev. E. 70, 011710 (2004)]. The periodic instability in a
      nematic sample induced by the saddle-splay elastic constant or by the coupling of
      an external field with the flexoelectric polarization is reconsidered. We show
      that in the case in which the two surfaces limiting the sample are characterized
      by the same easy angle the analysis previously proposed by us coincides with the
      one proposed by Virga.

PMID- 16090023
TI  - Clustering and the synchronization of oscillator networks.
AB  - By manipulating the clustering coefficient of a network without changing its
      degree distribution, we examine the effect of clustering on the synchronization
      of phase oscillators on networks with Poisson and scale-free degree
      distributions. For both types of networks, increased clustering hinders global
      synchronization as the network splits into dynamical clusters that oscillate at
      different frequencies. Surprisingly, in scale-free networks, clustering promotes
      the synchronization of the most connected nodes (hubs) even though it inhibits
      global synchronization. As a result, they show an additional, advanced transition
      instead of a single synchronization threshold. This cluster-enhanced
      synchronization of hubs may be relevant to the brain that is scale-free and
      highly clustered.

PMID- 16090024
TI  - Statistical mechanics of interfering links.
AB  - We consider the statistical mechanics of interfering transmissions in a wireless
      communications protocol. In this case, a connection between two nodes requires
      all other nodes within communication distance of the given two nodes to remain
      quiet on the given channel. This leads to an interesting problem of dimers on a
      lattice, with a restriction that no two dimers can overlap or be nearest
      neighbors. We consider both an equilibrium and a nonequilibrium, "greedy"
      dynamics for the links; the equilibrium properties of the model are found to
      exhibit an interesting spin-glass transition at maximum density on certain
      lattices, while the greedy construction is related to the problem of random
      sequential adsorption.

PMID- 16090025
TI  - Source coding by efficient selection of ground-state clusters.
AB  - We analyze the geometrical structure of clusters of ground states which appear in
      many frustrated systems over random graphs. Focusing on the regime of
      connectivities where the number of clusters is exponential in the size of the
      problems, we identify an appropriate generalization of the survey propagation
      equations efficiently exploring the geometry. The possibility of selecting
      different clusters has also computational consequences. As a proof of concept
      here we show how a well-known physical system can be used to perform nontrivial
      data compression, for which we introduce a unique compression scheme.
      Performances are optimized when the number of well-separated clusters is maximal
      in the underlying physical model.

PMID- 16090026
TI  - Predictability, bred vectors, and generation of ensembles in space-time chaotic
      systems.
AB  - Spatial configuration of initial errors strongly affects predictability of space
      time chaotic systems. The predictability of numerical models can be adjusted by
      using prepared ensembles of initial conditions. We present a natural way of
      preparing ensembles based in using finite-amplitude perturbations with varying
      correlation. This allows one to take into account the underlying dynamics to
      generate initial perturbations with spatial correlations varying from fully
      correlated (bred vectors) to random fluctuations.

PMID- 16090027
TI  - Test of steady-state fluctuation theorem in turbulent Rayleigh-Benard convection.
AB  - The local entropy production rate sigma (r,t) in turbulent thermal convection is
      obtained from simultaneous velocity and temperature measurements in an aspect
      ratio-one cell filled with water. The statistical properties of the time-averaged
      sigma (r,t) are analyzed and the results are compared with the predictions of the
      steady-state fluctuation theorem (SSFT) of Gallavotti and Cohen. The experiment
      reveals that the SSFT can indeed be extended to the local variables, but further
      development is needed in order to incorporate the common dynamic complexities of
      far-from-equilibrium systems into the theory.

PMID- 16090028
TI  - Hot-electron surface retention in intense short-pulse laser-matter interactions.
AB  - Implicit hybrid plasma simulations predict that a significant fraction of the
      energy deposited into hot electrons can be retained near the surface of targets
      with steep density gradients illuminated by intense short-pulse lasers. This
      retention derives from the lateral transport of heated electrons randomly emitted
      in the presence of spontaneous magnetic fields arising near the laser spot, from
      geometric effects associated with a small hot-electron source, and from E fields
      arising in reaction to the ponderomotive force. Below the laser spot hot
      electrons are axially focused into a target by the B fields, and can filament in
      moderate Z targets by resistive Weibel-like instability, if the effective
      background electron temperature remains sufficiently low. Carefully engineered
      use of such retention in conjunction with ponderomotive density profile
      steepening could result in a reduced hot-electron range that aids fast ignition.
      Alternatively, such retention may disturb a deeper deposition needed for
      efficient radiography and backside fast ion generation.

PMID- 16090029
TI  - Dimensional effects in dynamic fragmentation of brittle materials.
AB  - It has been shown previously that dynamic fragmentation of brittle D -dimensional
      objects in a D -dimensional space gives rise to a power-law contribution to the
      fragment-size distribution with a universal scaling exponent 2-1/D . We
      demonstrate that in fragmentation of two-dimensional brittle objects in three
      dimensional space, an additional fragmentation mechanism appears, which causes
      scale-invariant secondary breaking of existing fragments. Due to this mechanism,
      the power law in the fragment-size distribution has now a scaling exponent of
      approximately 1.17 .

PMID- 16090030
TI  - Percolation between vacancies in the two-dimensional Blume-Capel model.
AB  - Using suitable Monte Carlo methods and finite-size scaling, we investigate the
      Blume-Capel model on the square lattice. We construct percolation clusters by
      placing nearest-neighbor bonds between vacancies with a variable bond probability
      p(b) . At the tricritical point, we locate the percolation threshold of these
      vacancy clusters at p(bc) =0.706 33 (6) . At this point, we determine the fractal
      dimension of the vacancy clusters as Xf =0.1308 (5) approximately equal to
      21/160, and the exponent governing the renormalization flow in the p(b) direction
      as y(p) =0.426 (2) approximately equal to 17/40 . For bond probability p(b) >
      p(bc) , the vacancy clusters maintain strong critical correlations; the fractal
      dimension is Xf =0.0750 (2) approximately equal to 3/40 and the leading
      correction exponent is y(p) =-0.45 (2) approximately equal to -19/40 . The above
      values fit well in the Kac table for the tricritical Ising model. These vacancy
      clusters have much analogy with those consisting of Ising spins of the same sign,
      although the associated quantities rho and magnetization m are energylike and
      magnetic quantities, respectively. However, along the critical line of the Blume
      Capel model, the vacancies are more or less uniformly distributed over the whole
      lattice. In this case, no critical percolation correlations are observed in the
      vacancy clusters, at least in the physical region p(b) < or = 1 .

PMID- 16090031
TI  - Analytical results of asymmetric exclusion processes with ramps.
AB  - We present the analytical results in a simple traffic model describing a single
      lane highway with ramps. Both on-ramps and off-ramps are considered. Complete
      classification of distinct phases is achieved. Exact phase diagrams are derived.
      In the case of a single ramp (either on-ramp or off-ramp), the bottleneck effect
      is absent. The traffic conditions of congestion before the ramp and free-flowing
      after the ramp cannot be realized. In the case of two consecutive ramps, the
      bottleneck emerges when the on-ramp is placed before the off-ramp and the flow in
      between the ramps saturates.

PMID- 16090032
TI  - Static and dynamic length scales in a simple glassy plaquette model.
AB  - We study static and dynamic spatial correlations in a two-dimensional spin model
      with four-body plaquette interactions and standard Glauber dynamics by means of
      analytic arguments and Monte Carlo simulations. We study in detail the dynamical
      behavior which becomes glassy at low temperatures, due to the emergence of
      effective kinetic constraints in a dual representation where spins are mapped to
      plaquette variables. We study the interplay between nontrivial static
      correlations of the spins and the dynamic "four-point" correlations usually
      studied in the context of supercooled liquids. We show that slow dynamics is
      spatially heterogeneous due to the presence of diverging length scales and
      scaling, as is also found in kinetically constrained models. This analogy is
      illustrated by a comparative study of a froth model where the kinetic constraints
      are imposed.

PMID- 16090033
TI  - Quantum gas-liquid condensation in an attractive Bose gas.
AB  - Gas-liquid condensation (GLC) in an attractive Bose gas is studied on the basis
      of statistical mechanics. Using some results in combinatorial mathematics, the
      following are derived. (1) With decreasing temperature, the Bose-statistical
      coherence grows in the many-body wave function, which gives rise to the
      divergence of the grand partition function prior to Bose-Einstein condensation.
      It is a quantum-mechanical analogue to the GLC in a classical gas (quantum GLC).
      (2) This GLC is triggered by the bosons with zero momentum. Compared with the
      classical GLC, an incomparably weaker attractive force creates it. For the system
      showing the quantum GLC, we discuss a cold helium 4 gas at sufficiently low
      pressure.

PMID- 16090034
TI  - Universal aging properties at a disordered critical point.
AB  - We investigate, analytically near the dimension d(uc) =4 and numerically in d=3 ,
      the nonequilibrium relaxational dynamics of the randomly diluted Ising model at
      criticality. Using the exact renormalization-group method to one loop, we compute
      the two times t, t(w) correlation function and fluctuation dissipation ratio
      (FDR) for any Fourier mode of the order parameter, of finite wave vector q . In
      the large time separation limit, the FDR is found to reach a nontrivial value
      X(infinity) independently of (small) q and coincide with the FDR associated to
      the total magnetization obtained previously. Explicit calculations in real space
      show that the FDR associated to the local magnetization converges, in the
      asymptotic limit, to this same value X(infinity). Through a Monte Carlo
      simulation, we compute the autocorrelation function in three dimensions, for
      different values of the dilution fraction p at T(c) (p) . Taking properly into
      account the corrections to scaling, we find, according to the renormalization
      group predictions, that the autocorrelation exponent lambda(c) is independent of
      p . The analysis is complemented by a study of the nonequilibrium critical
      dynamics following a quench from a completely ordered state.

PMID- 16090035
TI  - Generalized percolation in random directed networks.
AB  - We develop a general theory for percolation in directed random networks with
      arbitrary two-point correlations and bidirectional edges--that is, edges pointing
      in both directions simultaneously. These two ingredients alter the previously
      known scenario and open new views and perspectives on percolation phenomena.
      Equations for the percolation threshold and the sizes of the giant components are
      derived in the most general case. We also present simulation results for a
      particular example of uncorrelated network with bidirectional edges confirming
      the theoretical predictions.

PMID- 16090036
TI  - Transition to strictly solitary motion in the Burridge-Knopoff model of
      multicontact friction.
AB  - We show that, in the continuous 1D Burridge-Knopoff model of multicontact
      friction, motion occurs via stick-slip sliding on a finite length rather than in
      avalanches, excluding the occurrence of self-organized criticality. We present
      strong numerical evidence that a transition from collective to strictly solitary
      motion occurs at a critical value of the interblock interactions. The solitary
      motion corresponds to successive stick-slip motion of one block between immobile
      neighbors, repeated periodically in time. This state persists also with open
      boundary conditions and moderate temperature.

PMID- 16090037
TI  - Highly optimized tolerance and power laws in dense and sparse resource regimes.
AB  - Power law cumulative frequency (P) versus event size (l) distributions P > or =l)
      approximately l(-alpha) are frequently cited as evidence for complexity and serve
      as a starting point for linking theoretical models and mechanisms with observed
      data. Systems exhibiting this behavior present fundamental mathematical
      challenges in probability and statistics. The broad span of length and time
      scales associated with heavy tailed processes often require special sensitivity
      to distinctions between discrete and continuous phenomena. A discrete highly
      optimized tolerance (HOT) model, referred to as the probability, loss, resource
      (PLR) model, gives the exponent alpha=1/d as a function of the dimension d of the
      underlying substrate in the sparse resource regime. This agrees well with data
      for wildfires, web file sizes, and electric power outages. However, another HOT
      model, based on a continuous (dense) distribution of resources, predicts
      alpha=1+1/d . In this paper we describe and analyze a third model, the cuts
      model, which exhibits both behaviors but in different regimes. We use the cuts
      model to show all three models agree in the dense resource limit. In the sparse
      resource regime, the continuum model breaks down, but in this case, the cuts and
      PLR models are described by the same exponent.

PMID- 16090038
TI  - Path-integral approach to dynamics in a sparse random network.
AB  - We study the dynamics involved in a sparse random network model. We extend the
      standard mean-field approximation for the dynamics of a random network by
      employing the path-integral approach. The result indicates that the distribution
      of the variable is essentially identical to that obtained from globally coupled
      oscillators with random Gaussian interaction. We present the results of a
      numerical simulation of the Kuramoto transition in a random network, which is
      found to be consistent with this analysis.

PMID- 16090039
TI  - Number of attractors in random Boolean networks.
AB  - The evaluation of the number of attractors in Kauffman networks by Samuelsson and
      Troein is generalized to critical networks with one input per node and to
      networks with two inputs per node and different probability distributions for
      update functions. A connection is made between the terms occurring in the
      calculation and between the more graphic concepts of frozen, nonfrozen, and
      relevant nodes, and relevant components. Based on this understanding, a
      phenomenological argument is given that reproduces the dependence of the
      attractor numbers on system size.

PMID- 16090040
TI  - Extinction of epidemics in lattice models with quenched disorder.
AB  - The extinction of the contact process for epidemics in lattice models with
      quenched disorder is analyzed in the limit of small density of infected sites. It
      is shown that the problem in such a regime can be mapped to the quantum
      mechanical one characterized by the Anderson Hamiltonian for an electron in a
      random lattice. It is demonstrated both analytically (self-consistent mean field)
      and numerically (by direct diagonalization of the Hamiltonian and by means of
      cellular automata simulations) that disorder enhances the contact process, given
      the mean values of random parameters are not influenced by disorder.

PMID- 16090041
TI  - Dynamics of book sales: endogenous versus exogenous shocks in complex networks.
AB  - We present an extensive study of the foreshock and aftershock signatures
      accompanying peaks of book sales. The time series of book sales are derived from
      the ranking system of Amazon.com. We present two independent ways of classifying
      peaks, one based on the acceleration pattern of sales and the other based on the
      exponent of the relaxation. They are found to be consistent and reveal the
      coexistence of two types of sales peaks: exogenous peaks occur abruptly and are
      followed by a power law relaxation, while endogenous sale peaks occur after a
      progressively accelerating power law growth followed by an approximately
      symmetrical power law relaxation which is slower than for exogenous peaks. We
      develop a simple epidemic model of buyers connected within a network of
      acquaintances which propagates rumors and opinions on books. The comparison
      between the predictions of the model and the empirical data confirms the validity
      of the model and suggests in addition that social networks have evolved to
      converge very close to criticality (here in the sense of critical branching
      processes of opinion spreading). We test in detail the evidence for a power law
      distribution of book sales and confirm a previous indirect study suggesting that
      the fraction of books (density distribution) P (S) of sales S is a power law P(S)
      approximately 1/ S(1+mu) with mu approximately equal to 2 .

PMID- 16090042
TI  - Ghost stochastic resonance in vertical-cavity surface-emitting lasers: experiment
      and theory.
AB  - We study the polarization response of a vertical-cavity surface-emitting laser,
      driven simultaneously by noise and two (or more) weak periodic signals. In the
      bistable regime, we observe experimentally the occurrence of stochastic resonance
      at a frequency that is absent in the input driving signal. The presence of this
      so-called ghost resonance is confirmed theoretically.

PMID- 16090043
TI  - Statistical mechanics model for the emergence of consensus.
AB  - The statistical properties of pairwise majority voting over S alternatives are
      analyzed in an infinite random population. We first compute the probability that
      the majority is transitive (i.e., that if it prefers A to B to C , then it
      prefers A to C) and then study the case of an interacting population. This is
      described by a constrained multicomponent random field Ising model whose
      ferromagnetic phase describes the emergence of a strong transitive majority. We
      derive the phase diagram, which is characterized by a tricritical point and show
      that, contrary to intuition, it may be more likely for an interacting population
      to reach consensus on a number S of alternatives when S increases. This effect is
      due to the constraint imposed by transitivity on voting behavior. Indeed if
      agents are allowed to express nontransitive votes, the agents' interaction may
      decrease considerably the probability of a transitive majority.

PMID- 16090044
TI  - Mechanism for nonequilibrium symmetry breaking and pattern formation in magnetic
      films.
AB  - Magnetic thin films exhibit a strong variation in properties depending on their
      degree of disorder. Recent coherent x-ray speckle experiments on magnetic films
      have measured the loss of correlation between configurations at opposite fields
      and at the same field, upon repeated field cycling. We perform finite temperature
      numerical simulations on these systems that provide a comprehensive explanation
      for the experimental results. The simulations demonstrate, in accordance with
      experiments, that the memory of configurations increases with film disorder. We
      find that nontrivial microscopic differences exist between the zero field spin
      configuration obtained by starting from a large positive field and the zero field
      configuration starting at a large negative field. This seemingly paradoxical
      behavior is due to the nature of the vector spin dynamics and is also seen in the
      experiments. For low disorder, there is an instability which causes the
      spontaneous growth of linelike domains at a critical field, also in accord with
      experiments. It is this unstable growth, which is highly sensitive to thermal
      noise, that is responsible for the small correlation between patterns under
      repeated cycling. The domain patterns, hysteresis loops, and memory properties of
      our simulated systems match remarkably well with the real experimental systems.

PMID- 16090045
TI  - Fractality of largest clusters and the percolation transition in power-law
      diluted chains.
AB  - Relying on the fractal character of the largest clusters at criticality, we
      employ a finite-size scaling analysis to obtain an accurate phase-diagram of the
      percolation transition in chains with bond concentration decaying as a power-law
      on the form 1/ r(1+sigma) . For the particular case of sigma=1, no percolation
      transition is observed to occur at a finite dilution, in contrast with the finite
      temperature Kosterlitz-Thouless transition exhibited in Ising and Potts chains
      with inverse square-law couplings. The fractal dimension of the critical
      percolation cluster is found to follow distinct dependencies on the decay
      exponent being numerically fitted by d(f) =0.35+4sigma/5 for 0<sigma<1/2 and d(f)
      = (1+sigma) /2 for 1/2<sigma<1 . We also compute average mass ratios of the two
      largest clusters at criticality.

PMID- 16090046
TI  - Control of local relaxation behavior in closed bipartite quantum systems.
AB  - We investigate the decoherence of a spin- 1/2 subsystem weakly coupled to an
      environment of many spins- 1/2 with and without mutual coupling. The total system
      is closed, its state is pure, and evolves under Schrodinger dynamics.
      Nevertheless, the considered spin typically reaches a quasistationary equilibrium
      state. Here we show that this state depends strongly on the coupling to the
      environment on the one hand and on the coupling within the environmental spins on
      the other. In particular we focus on spin star and spin ring-star geometries to
      investigate the effect of intra-environmental coupling on the central spin. By
      changing the spectrum of the environment, its effect as a bath on the central
      spin is also changed and may even be adjustable to some degree. We find that the
      relaxation behavior is related to the distribution of the energy eigenstates of
      the total system. For each of these relaxation modes, there is a dual mode for
      which the resulting subsystem approaches an inverted state occupation probability
      (negative temperature).

PMID- 16090047
TI  - Quantum scaling approach to nonequilibrium models.
AB  - Stochastic nonequilibrium exclusion models are treated using a real space scaling
      approach. The method exploits the mapping between nonequilibrium and quantum
      systems, and it is developed to accommodate conservation laws and duality
      symmetries, yielding exact fixed points for a variety of exclusion models. In
      addition, it is shown how the asymmetric simple exclusion process in one
      dimension can be written in terms of a classical Hamiltonian in two dimensions
      using a Suzuki-Trotter decomposition.

PMID- 16090048
TI  - Finite-size scaling of directed percolation above the upper critical dimension.
AB  - We consider analytically as well as numerically the finite-size scaling behavior
      in the stationary state near the nonequilibrium phase transition of directed
      percolation within the mean field regime, i.e., above the upper critical
      dimension. Analogous to equilibrium, usual finite-size scaling is valid below the
      upper critical dimension, whereas it fails above. Performing a momentum analysis
      of associated path integrals we derive modified finite-size scaling forms of the
      order parameter and its higher moments. The results are confirmed by numerical
      simulations of corresponding high-dimensional lattice models.

PMID- 16090049
TI  - Riemannian geometry of thermodynamics and systems with repulsive power-law
      interactions.
AB  - A Riemannian geometric theory of thermodynamics based on the postulate that the
      curvature scalar R is proportional to the inverse free energy density is used to
      investigate three-dimensional fluid systems of identical classical point
      particles interacting with each other via a power-law potential energy gamma r(
      alpha) . Such systems are useful in modeling melting transitions. The limit alpha
      ->infinity corresponds to the hard sphere gas. A thermodynamic limit exists only
      for short-range (alpha>3) and repulsive (gamma>0) interactions. The geometric
      theory solutions for given alpha>3 , gamma>0 , and any constant temperature T
      have the following properties: (1) the thermodynamics follows from a single
      function b (rho T(-3/alpha) ) , where rho is the density; (2) all solutions are
      equivalent up to a single scaling constant for rho T(-3/alpha) , related to gamma
      via the virial theorem; (3) at low density, solutions correspond to the ideal
      gas; (4) at high density there are solutions with pressure and energy depending
      on density as expected from solid state physics, though not with a Dulong-Petit
      heat capacity limit; (5) for 3<alpha<3.7913 , the solution goes from the low to
      the expected high density limit smoothly; (6) for alpha>3.7913 a phase transition
      is required to go between these regimes; (7) for any alpha>3 we may include a
      first-order phase transition, which is expected from computer simulations; and
      (8) if alpha-->infinity, the density approaches a finite value as the pressure
      increases to infinity, with the pressure diverging logarithmically in the density
      difference.

PMID- 16090050
TI  - Resistance distribution in the hopping percolation model.
AB  - We study the distribution function P (rho) of the effective resistance rho in two
      and three-dimensional random resistor networks of linear size L in the hopping
      percolation model. In this model each bond has a conductivity taken from an
      exponential form sigma proportional to exp (-kappar) , where kappa is a measure
      of disorder and r is a random number, 0< or = r < or =1 . We find that in both
      the usual strong-disorder regime L/ kappa(nu) >1 (not sensitive to removal of any
      single bond) and the extreme-disorder regime L/ kappa(nu) <1 (very sensitive to
      such a removal) the distribution depends only on L/kappa(nu) and can be well
      approximated by a log-normal function with dispersion b kappa(nu) /L , where b is
      a coefficient which depends on the type of lattice, and nu is the correlation
      critical exponent.

PMID- 16090051
TI  - Relationship between phase transitions and topological changes in one-dimensional
      models.
AB  - We address the question of the quantitative relationship between thermodynamic
      phase transitions and topological changes in the potential energy manifold
      analyzing two classes of one dimensional models, the Burkhardt solid-on-solid
      model and the Peyrard-Bishop model for DNA thermal denaturation, both in the
      confining and nonconfining version. These models, apparently, do not fit [M.
      Kastner, Phys. Rev. Lett. 93, 150601 (2004)] in the general idea that the phase
      transition is signaled by a topological discontinuity. We show that in both
      models the phase transition energy v(c) is actually noncoincident with, and
      always higher than, the energy v(theta) at which a topological change appears.
      However, applying a procedure already successfully employed in other cases as the
      mean field phi4 model, i.e., introducing a map M:v-->v(s) from levels of the
      energy hypersurface V to the level of the stationary points "visited" at
      temperature T, we find that M (v(c))=v(theta). This result enhances the relevance
      of the underlying stationary points in determining the thermodynamics of a
      system, and extends the validity of the topological approach to the study of
      phase transition to the elusive one-dimensional systems considered here.

PMID- 16090052
TI  - Accelerating, hyperaccelerating, and decelerating networks.
AB  - Many growing networks possess accelerating statistics where the number of links
      added with each new node is an increasing function of network size so the total
      number of links increases faster than linearly with network size. In particular,
      biological networks can display a quadratic growth in regulator number with
      genome size even while remaining sparsely connected. These features are mutually
      incompatible in standard treatments of network theory which typically require
      that every new network node possesses at least one connection. To model sparsely
      connected networks, we generalize existing approaches and add each new node with
      a probabilistic number of links to generate either accelerating,
      hyperaccelerating, or even decelerating network statistics in different regimes.
      Under preferential attachment for example, slowly accelerating networks display
      stationary scale-free statistics relatively independent of network size while
      more rapidly accelerating networks display a transition from scale-free to
      exponential statistics with network growth. Such transitions explain, for
      instance, the evolutionary record of single-celled organisms which display strict
      size and complexity limits.

PMID- 16090053
TI  - Beyond the Wigner distribution: Schrodinger equations and terrace width
      distributions.
AB  - The so-called generalized Wigner distribution has earlier been shown to be an
      excellent approximation for the terrace width distribution (TWD) of vicinal
      surfaces characterized by step-step interactions that are perpendicular to the
      average step direction and fall off as the inverse square of the step spacing. In
      this paper, we show that the generalized Wigner distribution can be derived from
      a plausible, phenomenological model in which two steps interact with each other
      directly and with other steps through a position-dependent pressure. We also
      discuss generalizations to more general step-step interactions and show that the
      predictions are in good agreement with TWDs derived from numerical transfer
      matrix calculations and Monte Carlo simulations. This phenomenological approach
      allows the step-step interaction to be extracted from experimental TWDs.

PMID- 16090054
TI  - Langevin simulation of the chirally decomposed sine-Gordon model.
AB  - A large class of quantum and statistical field theoretical models, encompassing
      relevant condensed matter and non-Abelian gauge systems, are defined in terms of
      complex actions. As the ordinary Monte Carlo methods are useless in dealing with
      these models, alternative computational strategies have been proposed along the
      years. The Langevin technique, in particular, is known to be frequently plagued
      with difficulties such as strong numerical instabilities or subtle ergodic
      behavior. Regarding the chirally decomposed version of the sine-Gordon model as a
      prototypical case for the failure of the Langevin approach, we devise a
      truncation prescription in the stochastic differential equations which yields
      numerical stability and is assumed not to spoil the Berezinskii-Kosterlitz
      Thouless transition. This conjecture is supported by a finite size scaling
      analysis, whereby a massive phase ending at a line of critical points is clearly
      observed for the truncated stochastic model.

PMID- 16090055
TI  - Monte Carlo study of the site-percolation model in two and three dimensions.
AB  - We investigate the site-percolation problem on the square and simple-cubic
      lattices by means of a Monte Carlo algorithm that in fact simulates systems with
      size L(d-1) x infinity, where L specifies the linear system size. This algorithm
      can be regarded either as an extension of the Hoshen-Kopelman method or as a
      special case of the transfer-matrix Monte Carlo technique. Various quantities,
      such as the magnetic correlation function, are sampled in the finite directions
      of the above geometry. Simulations are arranged such that both bulk and surface
      quantities can be sampled. On the square lattice, we locate the percolation
      threshold at p(c) =0.592 746 5 (4) , and determine two universal quantities as
      Q(gbc) =0.930 34 (1) and Q(gsc) =0.793 72 (3) , which are associated with bulk
      and surface correlations, respectively. These values agree well with the exact
      values 2(-5/48) and 2(-1/3) , respectively, which follow from conformal
      invariance. On the simple-cubic lattice, we locate the percolation threshold at
      p(c) =0.311 607 7 (4) . We further determine the bulk thermal and magnetic
      exponents as y(t) =1.1437 (6) and y(h) =2.5219 (2) , respectively, and the
      surface magnetic exponent at the ordinary phase transition as y (o)(hs) =1.0248
      (3) .

PMID- 16090056
TI  - First-exit times and residence times for discrete random walks on finite
      lattices.
AB  - In this paper, we derive explicit formulas for the surface averaged first-exit
      time of a discrete random walk on a finite lattice. We consider a wide class of
      random walks and lattices, including random walks in a nontrivial potential
      landscape. We also compute quantities of interest for modeling surface reactions
      and other dynamic processes, such as the residence time in a subvolume, the joint
      residence time of several particles, and the number of hits on a reflecting
      surface.

PMID- 16090057
TI  - Surface and bulk transitions in three-dimensional O(n) models.
AB  - Using Monte Carlo methods and finite-size scaling, we investigate surface
      criticality in the O(n) models on the simple-cubic lattice with n=1 , 2, and 3,
      i.e., the Ising, XY , and Heisenberg models. For the critical couplings we find
      Kc (n=2) =0.454 1659 (10) and Kc (n=3) =0.693 003 (2). We simulate the three
      models with open surfaces and determine the surface magnetic exponents at the
      ordinary transition to be y (o)(h1) =0.7374 (15) , 0.781 (2), and 0.813 (2) for
      n=1 , 2, and 3, respectively. Then we vary the surface coupling K1 and locate the
      so-called special transition at kappa(c) (n=1) =0.502 14 (8) and kappa(c) (n=2)
      =0.6222 (3), where kappa= K1 /K-1 . The corresponding surface thermal and
      magnetic exponents are y (s)(t1) =0.715 (1) and y (s)(h1) =1.636 (1) for the
      Ising model, and y(s)(t1) =0.608 (4) and y(s)(h1) =1.675 (1) for the XY model.
      Finite-size corrections with an exponent close to -1/2 occur for both models.
      Also for the Heisenberg model we find substantial evidence for the existence of a
      special surface transition.

PMID- 16090058
TI  - Coarsening dynamics in a two-species zero-range process.
AB  - We consider a zero-range process with two species of interacting particles. The
      steady-state phase diagram of this model shows a variety of condensate phases in
      which a single site contains a finite fraction of all the particles in the
      system. Starting from a homogeneous initial distribution, we study the coarsening
      dynamics in each of these condensate phases, which is expected to follow a
      scaling law. Random-walk arguments are used to predict the coarsening exponents
      in each condensate phase. They are shown to depend on the form of the hop rates
      and on the symmetry of the hopping dynamics. The analytic predictions are found
      to be in good agreement with the results of Monte Carlo simulations.

PMID- 16090059
TI  - Universal critical behavior of noisy coupled oscillators: a renormalization group
      study.
AB  - We show that the synchronization transition of a large number of noisy coupled
      oscillators is an example for a dynamic critical point far from thermodynamic
      equilibrium. The universal behaviors of such critical oscillators, arranged on a
      lattice in a d -dimensional space and coupled by nearest-neighbors interactions,
      can be studied using field-theoretical methods. The field theory associated with
      the critical point of a homogeneous oscillatory instability (or Hopf bifurcation
      of coupled oscillators) is the complex Ginzburg-Landau equation with additive
      noise. We perform a perturbative renormalization group (RG) study in a (4
      epsilon)-dimensional space. We develop an RG scheme that eliminates the phase and
      frequency of the oscillations using a scale-dependent oscillating reference
      frame. Within Callan-Symanzik's RG scheme to two-loop order in perturbation
      theory, we find that the RG fixed point is formally related to the one of the
      model A dynamics of the real Ginzburg-Landau theory with an O2 symmetry of the
      order parameter. Therefore, the dominant critical exponents for coupled
      oscillators are the same as for this equilibrium field theory. This formal
      connection with an equilibrium critical point imposes a relation between the
      correlation and response functions of coupled oscillators in the critical regime.
      Since the system operates far from thermodynamic equilibrium, a strong violation
      of the fluctuation-dissipation relation occurs and is characterized by a
      universal divergence of an effective temperature. The formal relation between
      critical oscillators and equilibrium critical points suggests that long-range
      phase order exists in critical oscillators above two dimensions.

PMID- 16090060
TI  - Surface-element analysis of spatiotemporal stripe patterns formed by Ag and Sb
      coelectrodeposition.
AB  - Various spatiotemporal patterns of light and dark stripes are formed in the Ag
      and Sb coelectrodeposition system. In this research, we report the results of the
      element analysis of three spatiotemporal stripe patterns using an electron probe
      (x-ray) microanalyzer. The results indicate that all the patterns have an O
      distribution reflecting the color configuration of the patterns, in addition to
      Ag and Sb distributions, which have been advocated as forming the patterns. It is
      suggested that O, as well as Ag and Sb, contributes to the formation of the
      patterns.

PMID- 16090061
TI  - Dynamic characterizers of spatiotemporal intermittency.
AB  - We study spatiotemporal intermittency (STI) in a system of coupled sine circle
      maps. The phase diagram of the system shows parameter regimes where the STI lies
      in the directed percolation (DP) class, as well as regimes which show pure
      spatial intermittency (where the temporal behavior is regular) which do not
      belong to the DP class. Thus both DP and non-DP behavior can be seen in the same
      system. The signature of DP and non-DP behavior can be seen in the dynamic
      characterizers, viz. the spectrum of eigenvalues of the linear stability matrix
      of the evolution equation, as well as in the multifractal spectrum of the
      eigenvalue distribution. The eigenvalue spectrum of the system in the DP regimes
      is continuous, whereas it shows evidence of level repulsion in the form of gaps
      in the spectrum in the non-DP regime. The multifractal spectrum of the eigenvalue
      distribution also shows the signature of DP and non-DP behavior. These results
      have implications for the manner in which correlations build up in extended
      systems.

PMID- 16090062
TI  - Ising-Bloch transition for spatially extended patterns.
AB  - The Ising-Bloch transition for domain walls in spatially extended nonlinear
      systems is a known phenomenon. We show a similar transition for extended
      patterns, such as labyrinths and stripes. The analysis is performed in the frame
      of the parametrically driven Ginzburg-Landau equation, which is a paradigmatic
      model for a variety on nonlinear systems showing the Ising-Bloch transition of
      domain walls.

PMID- 16090063
TI  - Hydrodynamic coarsening in striped pattern formation with a conservation law.
AB  - We observed in numerical simulations that the interaction of striped-pattern
      forming instability and a neutrally stable zero mode induces patterns of domains
      of upflow hexagons coexisting with domains of downflow hexagons. They appear only
      when hydrodynamic flow is present.

PMID- 16090064
TI  - Phase synchronization between two essentially different chaotic systems.
AB  - In this paper, we numerically investigate phase synchronization between two
      coupled essentially different chaotic oscillators in drive-response
      configuration. It is shown that phase synchronization can be observed between two
      coupled systems despite the difference and the large frequency detuning between
      them. Moreover, the relation between phase synchronization and generalized
      synchronization is compared with that in coupled parametrically different
      systems. In the systems studied, it is found that phase synchronization occurs
      after generalized synchronization in coupled essentially different chaotic
      systems.

PMID- 16090065
TI  - Controlling dynamical systems using multiple delay feedback control.
AB  - Multiple delay feedback control (MDFC) with two, three, or four different and
      independent delay times is used to stabilize steady states of various chaotic
      dynamical systems. A comparison with delayed feedback control methods that are
      based on a single (fundamental) delay time [Pyragas' time delay auto
      synchronization (TDAS) and extended TDAS] shows that MDFC is more effective for
      fixed point stabilization in terms of stability and flexibility, in particular
      for large delay times.

PMID- 16090066
TI  - Spatial coherence resonance in excitable media.
AB  - We study the phenomenon of spatial coherence resonance in a two-dimensional model
      of excitable media with FitzHugh-Nagumo local dynamics. In particular, we show
      that there exists an optimal level of additive noise for which an inherent
      spatial scale of the excitable media is best pronounced. We argue that the
      observed phenomenon occurs due to the existence of a noise robust excursion time
      that is characteristic for the local dynamics whereby the diffusion constant,
      representing the rate of diffusive spread, determines the actual resonant spatial
      frequency. Additionally, biological implications of presented results in the
      field of neuroscience are outlined.

PMID- 16090067
TI  - Localization of Floquet states along a continuous line of periodic orbits.
AB  - A periodically driven particle in an infinite square well is shown to exhibit
      quantum localization due to a continuous line of periodic orbits in the classical
      system. Individual Floquet eigenstates localized along this line of periodic
      orbits are identified. The enhanced localization persists for field strengths
      beyond that at which the continuous line of orbits is destroyed in the classical
      dynamics. These results may be relevant to experiments involving trapping
      potentials with flat regions.

PMID- 16090068
TI  - Sand ripples under water with complex wave motion.
AB  - Experiments studying ripple formation under water have usually used sinusoidal
      driving force. Here an experiment is presented where the driving force can be an
      arbitrary wave form, thus trying to mimic the realistic wave motion in shallow
      water coastal zones. We study a simple modulated sine wave and more complicated
      wave forms with several superposed harmonics. In particular we demonstrate how a
      small higher order harmonic can have a dramatic effect on the wavelength of the
      ripple pattern.

PMID- 16090069
TI  - Estimation of coupling between time-delay systems from time series.
AB  - We propose a method for estimation of coupling between the systems governed by
      scalar time-delay differential equations of the Mackey-Glass type from the
      observed time series data. The method allows one to detect the presence of
      certain types of linear coupling between two time-delay systems, to define the
      type, strength, and direction of coupling, and to recover the model equations of
      coupled time-delay systems from chaotic time series corrupted by noise. We verify
      our method using both numerical and experimental data.

PMID- 16090070
TI  - Synchronized clusters in coupled map networks. I. Numerical studies.
AB  - We study the synchronization of coupled maps on a variety of networks including
      regular one- and two-dimensional networks, scale-free networks, small world
      networks, tree networks, and random networks. For small coupling strengths nodes
      show turbulent behavior but form phase synchronized clusters as coupling
      increases. When nodes show synchronized behavior, we observe two interesting
      phenomena. First, there are some nodes of the floating type that show
      intermittent behavior between getting attached to some clusters and evolving
      independently. Second, we identify two different ways of cluster formation,
      namely self-organized clusters which have mostly intracluster couplings and
      driven clusters which have mostly intercluster couplings. The synchronized
      clusters may be of dominant self-organized type, dominant driven type, or mixed
      type depending on the type of network and the parameters of the dynamics. We
      define different states of the coupled dynamics by considering the number and
      type of synchronized clusters. For the local dynamics governed by the logistic
      map we study the phase diagram in the plane of the coupling constant (epsilon)
      and the logistic map parameter (mu). For large coupling strengths and nonlinear
      coupling we find that the scale-free networks and the Caley tree networks lead to
      better cluster formation than the other types of networks with the same average
      connectivity. For most of our study we use the number of connections of the order
      of the number of nodes. As the number of connections increases the number of
      nodes forming clusters and the size of the clusters in general increase.

PMID- 16090071
TI  - Synchronized clusters in coupled map networks. II. Stability analysis.
AB  - We study self-organized and driven synchronization in some simple coupled map
      networks, namely globally coupled networks and complete bipartite networks, using
      both linear stability analysis and Lyapunov function approach and determine
      stability conditions for synchronization. The phase diagrams for the networks
      studied here have features very similar to the different kinds of structurally
      similar networks studied in Part I. Lyapunov function approach shows that when
      any two nodes are in driven synchronization, all the coupling terms in the
      difference between the variables of these two nodes cancel out, whereas when they
      are in self-organized synchronization, the direct coupling term between the two
      nodes adds an extra term while the other couplings cancel out. We also discuss
      the conditions for the occurrence of a floating node and suggest that the
      fluctuations of the conditional Lyapunov exponent about zero can be a criterion
      for its occurrence.

PMID- 16090072
TI  - Relativistic kicked rotor.
AB  - Transport properties in the relativistic analog of the periodically kicked rotor
      are contrasted under classically and quantum mechanical dynamics. The quantum
      rotor is treated by solving the Dirac equation in the presence of the time
      periodic delta-function potential resulting in a relativistic quantum mapping
      describing the evolution of the wave function. The transition from the quantum
      suppression behavior seen in the nonrelativistic limit to agreement between
      quantum and classical analyses in the relativistic regime is discussed. The
      absence of quantum resonances in the relativistic case is also addressed.

PMID- 16090073
TI  - Public-channel cryptography using chaos synchronization.
AB  - We present a key-exchange protocol that comprises two parties with chaotic
      dynamics that are mutually coupled and undergo a synchronization process, at the
      end of which they can use their identical dynamical state as an encryption key.
      The transferred coupling- signals are based nonlinearly on time-delayed states of
      the parties, and therefore they conceal the parties' current state and can be
      transferred over a public channel. Synchronization time is linear in the number
      of synchronized digits alpha, while the probability for an attacker to
      synchronize with the parties drops exponentially with alpha. To achieve security
      with finite alpha we use a network.

PMID- 16090074
TI  - Instability threshold of a photorefractive pattern-forming system.
AB  - We report on the detailed experimental determination of the threshold for
      modulational instability in a photorefractive single-mirror feedback system using
      a Fourier control technique. Results are compared to analytical predictions and a
      disagreement for the experimentally significant multiple pattern region is found.
      Implications for the generation of nonhexagonal two-dimensional patterns are
      discussed.

PMID- 16090075
TI  - Thresholds of excitability in three-dimensional dynamical systems.
AB  - A two-dimensional threshold surface of an excitable system is found as a set of
      threshold trajectories calculated step by step in cross sections of the phase
      space. The method leads to a highly nonlinear boundary value problem that can be
      solved numerically with the use of adaptive multiple shooting and continuation
      methods. We demonstrate this technique by examining a model of a biochemical
      oscillator with two positive feedbacks. Generalization to arbitrary dimension is
      discussed.

PMID- 16090076
TI  - Graph operations and synchronization of complex networks.
AB  - The effects of graph operations on the synchronization of coupled dynamical
      systems are studied. The operations range from addition or deletion of links to
      various ways of combining networks and generating larger networks from simpler
      ones. Methods from graph theory are used to calculate or estimate the eigenvalues
      of the Laplacian operator, which determine the synchronizability of continuous or
      discrete time dynamics evolving on the network. Results are applied to explain
      numerical observations on random, scale-free, and small-world networks. An
      interesting feature is that, when two networks are combined by adding links
      between them, the synchronizability of the resulting network may worsen as the
      synchronizability of the individual networks is improved. Similarly, adding links
      to a network may worsen its synchronizability, although it decreases the average
      distance in the graph.

PMID- 16090077
TI  - Quantitative analysis of chaotic synchronization by means of coherence.
AB  - We use an index of chaotic synchronization based on the averaged coherence
      function for the quantitative analysis of the process of the complete
      synchronization loss in unidirectionally coupled oscillators and maps. We
      demonstrate that this value manifests different stages of the synchronization
      breaking. It is invariant to time delay and insensitive to small noise and
      distortions, which can influence the accessible signals at measurements.
      Peculiarities of the synchronization destruction in maps and oscillators are
      investigated.

PMID- 16090078
TI  - Spectral density of the correlation matrix of factor models: a random matrix
      theory approach.
AB  - We studied the eigenvalue spectral density of the correlation matrix of factor
      models of multivariate time series. By making use of the random matrix theory, we
      analytically quantified the effect of statistical uncertainty on the spectral
      density due to the finiteness of the sample. We considered a broad range of
      models, ranging from one-factor models to hierarchical multifactor models.

PMID- 16090079
TI  - Properties making a chaotic system a good pseudo random number generator.
AB  - We discuss the properties making a deterministic algorithm suitable to generate a
      pseudo random sequence of numbers: high value of Kolmogorov-Sinai entropy, high
      dimensionality of the parent dynamical system, and very large period of the
      generated sequence. We propose the multidimensional Anosov symplectic (cat) map
      as a pseudo random number generator. We show what chaotic features of this map
      are useful for generating pseudo random numbers and investigate numerically which
      of them survive in the discrete state version of the map. Testing and comparisons
      with other generators are performed.

PMID- 16090080
TI  - Rapidly decorrelating velocity-field model as a tool for solving one-point Fokker
      Planck equations for probability density functions of turbulent reactive scalars.
AB  - Light is shed upon Eulerian Monte Carlo methods and their application to the
      simulation of turbulent reactive flows. A rapid decorrelating velocity-field
      model is used to derive stochastic partial differential equations (SPDE's)
      stochastically equivalent to the modeled one-point joint probability density
      function of turbulent reactive scalars. Those SPDE's are shown to be hyperbolic,
      advection-reaction equations. They are dealt with in a generalized sense, so that
      discontinuities in the scalar fields can be treated. A numerical analysis is
      proposed and numerical tests are carried out. In particular, a comparison with
      the Lagrangian Monte Carlo method is performed.

PMID- 16090081
TI  - Group-theoretical model of developed turbulence and renormalization of the Navier
      Stokes equation.
AB  - On the basis of the Euler equation and its symmetry properties, this paper
      proposes a model of stationary homogeneous developed turbulence. A regularized
      averaging formula for the product of two fields is obtained. An equation for the
      averaged turbulent velocity field is derived from the Navier-Stokes equation by
      renormalization-group transformation.

PMID- 16090082
TI  - Effect of patterned slip on micro- and nanofluidic flows.
AB  - We consider the flow of a Newtonian fluid in a nano- or microchannel with walls
      that have patterned variations in slip length. We formulate a set of equations to
      describe the effects on an incompressible Newtonian flow of small variations in
      slip and solve these equations for slow flows. We test these equations using
      molecular dynamics simulations of flow between two walls which have patterned
      variations in wettability. Good qualitative agreement and a reasonable degree of
      quantitative agreement is found between the theory and molecular dynamics
      simulations. The results of both analyses show that patterned wettability can be
      used to induce complex variations in flow. Finally we discuss the implications of
      our results for the design of microfluidic mixers using slip.

PMID- 16090083
TI  - Luminescence spectra of laser-induced cavitation bubbles near rigid boundaries.
AB  - The luminescence spectra of laser-induced cavitation bubbles near rigid
      boundaries are measured for various relative distances between the bubble and the
      boundaries. We find that the luminescence spectra of bubbles collapsing near a
      single boundary consist only of a blackbody continuum. Luminescence from bubbles
      collapsing between two parallel rigid boundaries contains O H- emission bands
      similar to those found in multibubble sonoluminescence. In both cases, the bubble
      interior temperature deduced from blackbody fits decreases with the distance
      between bubble and boundary. The shape instabilities of the collapse near a
      boundary and the consequent presence of high-velocity jets inside the bubble at
      its minimum volume are discussed in connection with the generation of the O H-
      radicals.

PMID- 16090084
TI  - Additive equivalence in turbulent drag reduction by flexible and rodlike
      polymers.
AB  - We address the additive equivalence discovered by Virk and co-workers: drag
      reduction affected by flexible and rigid rodlike polymers added to turbulent wall
      bounded flows is limited from above by a very similar maximum drag reduction
      (MDR) asymptote. Considering the equations of motion of rodlike polymers in wall
      bounded turbulent ensembles, we show that although the microscopic mechanism of
      attaining the MDR is very different, the macroscopic theory is isomorphic,
      rationalizing the interesting experimental observations.

PMID- 16090085
TI  - Scaling laws for unsteady natural convection cooling of fluid with Prandtl number
      less than one in a vertical cylinder.
AB  - The flow behavior associated with cooling an initially quiescent isothermal
      Newtonian fluid with Prandtl number (Pr) less than one in a vertical cylinder by
      unsteady natural convection with an imposed lower temperature on vertical
      sidewalls is investigated by scaling analysis and direct numerical simulation.
      The flow is dominated by three distinct stages of development, i.e., the boundary
      layer development stage adjacent to the sidewall, the stratification stage, and
      the cooling-down stage, respectively. The first stage can be further divided into
      three distinct substages, i.e., the start-up stage, the transitional stage, and
      the boundary-layer steady-state stage, respectively. A scaling analysis is
      carried out to obtain scaling laws for the basic flow features in terms of the
      flow control parameters, i.e., the Rayleigh number Ra, Pr, and the aspect ratio
      of the cylinder A , respectively. A series of direct numerical simulations with
      selected values of A , Ra, and Pr in the ranges of 1/3< or = A< or =3, 10(6) < or
      =Ra < or = 10(10) , and 0.01< or =Pr< or =0.5 are carried out, and it is found
      that the numerical results agree well with the scaling laws. These numerical
      results are further used to quantify these scaling laws for Ra, A , and Pr in the
      above-mentioned ranges.

PMID- 16090086
TI  - Infrared decimation renormalization-group calculations for two-dimensional test
      field turbulence.
AB  - We perform a decimation of modes starting from the infrared end of wave numbers
      on the randomly stirred test-field dynamics augmented by linear (Rayleigh) drag
      terms to model turbulence in two dimensions. A renormalization-group scheme shows
      relevant corrections to the drag coefficients and the existence of ultraviolet
      attractive fixed points, facilitating calculations of the universal numbers in
      both the energy and the enstrophy regimes. Marginal behavior in the enstrophy
      range yields logarithmic renormalization. We make a detailed comparison of the
      renormalization-group results with the numerical and analytical results following
      from Kraichnan's test-field closure.

PMID- 16090088
TI  - Eulerian spectral closures for isotropic turbulence using a time-ordered
      fluctuation-dissipation relation.
AB  - Procedures for time-ordering the covariance function, as given in a previous
      paper [K. Kiyani and W. D. McComb, Phys. Rev. E 70, 066303 (2004)], are extended
      and used to show that the response function associated at second order with the
      Kraichnan-Wyld perturbation series can be determined by a local (in wave number)
      energy balance. These time-ordering procedures also allow the two-time
      formulation to be reduced to time-independent form by means of exponential
      approximations and it is verified that the response equation does not have an
      infrared divergence at infinite Reynolds number. Last, single-time Markovianized
      closure equations (stated in our previous paper) are derived and shown to be
      compatible with the Kolmogorov distribution without the need to introduce an ad
      hoc constant.

PMID- 16090087
TI  - Measurements of the bulk and interfacial velocity profiles in oscillating
      Newtonian and Maxwellian fluids.
AB  - We present the dynamic velocity profiles of a Newtonian fluid (glycerol) and a
      viscoelastic Maxwell fluid (CPyCl-NaSal in water) driven by an oscillating
      pressure gradient in a vertical cylindrical pipe. The frequency range explored
      has been chosen to include the first three resonance peaks of the dynamic
      permeability of the viscoelastic-fluid--pipe system. Three different optical
      measurement techniques have been employed. Laser Doppler anemometry has been used
      to measure the magnitude of the velocity at the center of the liquid column.
      Particle image velocimetry and optical deflectometry are used to determine the
      velocity profiles at the bulk of the liquid column and at the liquid-air
      interface respectively. The velocity measurements in the bulk are in good
      agreement with the theoretical predictions of a linear theory. The results,
      however, show dramatic differences in the dynamic behavior of Newtonian and
      viscoelastic fluids, and demonstrate the importance of resonance phenomena in
      viscoelastic fluid flows, biofluids in particular, in confined geometries.

PMID- 16090089
TI  - Parametric autoresonance in Faraday waves.
AB  - We develop a theory of parametric excitation of weakly nonlinear standing gravity
      waves in a tank, which is under vertical vibrations with a slowly time-dependent
      ("chirped") vibration frequency. We show that, by using a negative chirp, one can
      excite a steadily growing wave via parametric autoresonance. The method of
      averaging is employed to derive the governing equations for the primary mode.
      These equations are solved analytically and numerically, for typical initial
      conditions, for both inviscid and weakly viscous fluids. It is shown that, when
      passing through resonance, capture into resonance always occurs when the chirp
      rate is sufficiently small. The critical chirp rate, above which breakdown of
      autoresonance occurs, is found for different initial conditions. The
      autoresonance excitation is expected to terminate at large amplitudes, when the
      underlying constant-frequency system ceases to exhibit a nontrivial stable fixed
      point.

PMID- 16090090
TI  - Extraction of coherent structures in a rotating turbulent flow experiment.
AB  - The discrete wavelet transform (DWT) and discrete wavelet packet transform (DWPT)
      are used to extract and study the dynamics of coherent structures in a turbulent
      rotating fluid. Three-dimensional turbulence is generated by strong pumping
      through tubes at the bottom of a rotating tank (48.4 cm high, 39.4 cm diameter).
      This flow evolves toward two-dimensional (2D) turbulence with increasing height
      in the tank. Particle image velocimetry measurements on the quasi-2D flow reveal
      many long-lived coherent vortices with a wide range of sizes. The vorticity field
      exhibits vortex creation, merger, scattering, and destruction. We separate the
      flow into a low-entropy "coherent" and a high-entropy "incoherent" component by
      thresholding the coefficients of the DWT and DWPT of the vorticity field. Similar
      thresholdings using the Fourier transform and JPEG compression together with the
      Okubo-Weiss criterion are also tested for comparison. We find that the DWT and
      DWPT yield similar results and are much more efficient at representing the total
      flow than a Fourier-based method. Only about 3% of the large-amplitude
      coefficients of the DWT and DWPT are necessary to represent the coherent
      component and preserve the vorticity probability distribution function (PDF),
      transport properties, and spatial and temporal correlations. The remaining small
      amplitude coefficients represent the incoherent component, which has near
      Gaussian vorticity PDF, contains no coherent structures, rapidly loses
      correlation in time, and does not contribute significantly to the transport
      properties of the flow. This suggests that one can describe and simulate such
      turbulent flow using a relatively small number of wavelet or wavelet packet
      modes.

PMID- 16090091
TI  - Does a fast mixer really exist?
AB  - In this paper, we are concerned about the limit behavior of the decay rate of
      variance of a passive and diffusive scalar in a flow field as the diffusivity of
      the scalar goes to zero. Motivated by the concept of the fast dynamo in the
      dynamo theory, we term a flow as fast mixer if the decay rate remains away from
      zero as the diffusivity goes to zero. We first repeat numerical simulations with
      flow maps and velocity fields used in the existing literature, including the
      lattice map, the 1D baker's map, and the sinusoidal shear flow. Our simulations
      shows that, in all cases, the decay rate tends to zero as the diffusivity goes to
      zero. For the closed flows in a bounded domain, we then theoretically proved this
      result under certain plausible conditions on the flows. For the open flows in the
      whole space, we show that the effective diffusivity matrix tends to zero in the
      limit without the conditions for the closed flow. In conclusion, although a fast
      mixer might exist, it could be very difficult to find one.

PMID- 16090092
TI  - Surface wave propagation of thin liquid films on a rotating and nonrotating disk.
AB  - We theoretically and numerically study the evolution of axisymmetrical surface
      waves of a wetting liquid film on a rotating or nonrotating disk. Shock waves may
      form and propagate driven by the centrifugal and external shearing forces.
      Surface tension and disjoining pressure due to van der Waals force provide
      diffusion to the system and smear the surface waves. Multiple waves of a
      molecularly thin liquid film are merged by the disjoining pressure. Surface waves
      are planarized by the centrifugal force, surface tension, external shearing force
      and disjoining pressure.

PMID- 16090093
TI  - Influence of the excited states on the electron-energy distribution function in
      low-pressure microwave argon plasmas.
AB  - In this work the influence of the excited states on the electron-energy
      distribution function has been determined for an argon microwave discharge at low
      pressure. A collisional-radiative model of argon has been developed taking into
      account the most recent experimental and theoretical values of argon-electron
      impact excitation cross sections. The model has been solved along with the
      electron Boltzmann equation in order to study the influence of the inelastic
      collisions from the argon excited states on the electron-energy distribution
      function. Results show that under certain conditions the excited states can play
      an important role in determining the shape of the distribution function and the
      mean kinetic energy of the electrons, deplecting the high-energy tail due to
      inelastic processes from the excited states, especially from the 4s excited
      configuration. It has been found that from the populations of the excited states
      an excitation temperature can be defined. This excitation temperature, which can
      be experimentally determined by optical emission spectroscopy, is lower than the
      electron kinetic temperature obtained from the electron-energy distribution
      function.

PMID- 16090094
TI  - Model for the density, temperature, and plasma potential of low-density hot
      filament discharges.
AB  - A theoretical model is developed for the density and temperature of confined
      electrons and the plasma potential in low-density hot-filament discharges. These
      three parameters are found from a simultaneous solution of the equations for ion
      particle balance, electron particle balance, and electron energy balance. In the
      model, electrons are lost by diffusion in velocity over the potential barrier
      determined by the plasma potential. The confined electrons are heated by the
      unconfined electrons that are the secondaries from the wall and, to a lesser
      extent, by the primary electrons from the filaments. The plasma parameters
      calculated from the model agree with parameters measured in a double plasma
      device that has been modified to have a clean wall that gives a single value for
      the confining potential.

PMID- 16090095
TI  - Electromagnetic instabilities for relativistic beam-plasma interaction in whole k
      space: nonrelativistic beam and plasma temperature effects.
AB  - For the system formed by a relativistic electron beam and its plasma return
      current, we investigate the effects of both transverse and parallel beam and
      plasma temperatures on the linear stability of collective electromagnetic modes.
      We focus on nonrelativistic temperatures and wave-vector orientations ranging
      from two-stream to filamentation instabilities. Water-bag distributions are used
      to model temperature effects and we discuss their relevance. Labeling Theta(k)
      the angle between the beam and the wave vector, one or two critical angles
      Theta(c,i) are determined exactly and separate the k space into two parts. Modes
      with Theta(k) < Theta(c) =min ( Theta(c,i)) are quasilongitudinal and poorly
      affected by any kind of temperature. Modes having Theta(k) > Theta(c) are very
      sensitive to transverse beam and plasma parallel temperatures. Also, parallel
      plasma temperature can trigger a transition between the beam-dependent
      filamentation instability (Theta(k) =pi/2) and the plasma-temperature-dependent
      Weibel instability so that two-stream, filamentation, and Weibel instabilities
      are eventually closely connected to each other. The maximum growth rate being
      reached for a mode with Theta(k) < Theta(c), no temperature of any kind can
      significantly reduce it in the nonrelativistic temperature regime.

PMID- 16090096
TI  - Detailed diagnostics for a hot bromine plasma by the open M-shell opacity.
AB  - The experimental transmission spectrum of a hot bromine plasma [J. E. Bailey, J.
      Quant. Spectrosc. Radiat. Transf. 81, 31 (2003)] has been simulated by using a
      detailed level accounting model (DLA). With assumption of the local thermodynamic
      equilibrium, the major absorption lines of the experimental spectrum are well
      reproduced by the present DLA calculation, and the details of the absorption line
      shapes are used to determine the temperature of the plasma. In contrast to the
      results of two former statistical models, where the temperature was determined
      via a global fitting to the experimental data, the present DLA diagnoses the
      plasma temperature by the line ratios of different charge states in the 2p-->3d
      transition groups resulting in a temperature of 37 eV . It is shown that a change
      of 1 eV in temperature could cause perceptible changes in the simulated spectrum.
      It is also shown that the 2 p1/2 -->3 d3/2 absorptions have been overestimated by
      the statistical models.

PMID- 16090097
TI  - Ion drag force in plasmas at high electronegativity.
AB  - The electric as well as the positive- and negative-ion drag forces on an isolated
      dust grain in an electronegative plasma are studied for large negative-ion
      densities, when the negative ions are not Boltzmann distributed. The
      investigation is carried out for submicrometer dust particles, so that the theory
      of Coulomb scattering is applicable for describing ion-dust interaction. Among
      the forces acting on the dust grain, the negative-ion drag force is found to be
      important. The effects of the negative-ion density, neutral-gas pressure, and
      dust-grain size on the forces are also considered. It is shown that by increasing
      the density of the negative ions one can effectively manipulate the dust grains.
      Our results imply that both dust voids and balls can be formed.

PMID- 16090098
TI  - Particle charge in the bulk of gas discharges.
AB  - An experimental determination of particle charge in a bulk dc discharge plasma
      covering a wide range of neutral gas pressures, was recently reported [S.
      Ratynskaia, Phys. Rev. Lett. 93, 085001 (2004)]. The charges obtained were
      several times smaller than the predictions of collisionless orbital motion
      limited theory. This discrepancy was attributed to the effect of ion-neutral
      collisions. In the present paper a more detailed description of this experiment
      is provided and additional experimental results obtained with particles of
      different sizes are reported. The measurements are compared with molecular
      dynamics simulations of particle charging for conditions similar to those of the
      experiment, with other available experimental data on particle charge in the bulk
      of gas discharges, and with a simple analytical model accounting for ion-neutral
      collisions. All the considered evidence indicates that ion-neutral collisions
      represent a very important factor, which significantly affects (reduces) the
      particle charge under typical discharge conditions.

PMID- 16090099
TI  - Statistical model for intermittent plasma edge turbulence.
AB  - The probability distribution function of plasma density fluctuations at the edge
      of fusion devices is known to be skewed and strongly non-Gaussian. The causes of
      this peculiar behavior are, up to now, largely unexplored. On the other hand,
      understanding the origin and the properties of edge turbulence is a key issue in
      magnetic fusion research. In this paper we show that a stochastic fragmentation
      model, already successfully applied to fluid turbulence, is able to predict an
      asymmetric distribution that closely matches experimental data. The asymmetry is
      found to be a direct consequence of intermittency. A discussion of our results in
      terms of recently suggested Bramwell-Holdsworth-Pinton universal curve [S. T.
      Bramwell, P. C. W. Holdsworth, and J.-F. Pinton, Nature (London) 396, 552
      (1998)], that should hold for strongly correlated and critical systems, is also
      proposed.

PMID- 16090100
TI  - Higher harmonic inverse free-electron laser interaction.
AB  - We expand the theory of the inverse free electron laser (IFEL) interaction to
      include the possibility of energy exchange that takes place when relativistic
      particles traversing an undulator interact with an electromagnetic wave of a
      frequency that is a harmonic of the fundamental wiggler resonant frequency. We
      derive the coupling coefficients as a function of the IFEL parameters for all
      harmonics, both odd and even. The theory is supported by simulation results
      obtained with a three-dimensional Lorentz equation solver code. Comparisons are
      made between the results of theory and simulations, and the recent UCLA IFEL
      experimental results where higher harmonic IFEL interaction was observed.

PMID- 16090101
TI  - Autosoliton propagation and mapping problem in optical fiber lines with lumped
      nonlinear devices.
AB  - A theoretical model is developed to describe the propagation of ultrashort
      optical pulses in fiber transmission systems in the quasilinear regime, with
      periodically inserted in-line nonlinear optical devices.

PMID- 16090102
TI  - Trapping force on a finite-sized particle in a dielectrophoretic cage.
AB  - The point dipole (PD) model is routinely used for estimating the
      dielectrophoretic (DEP) force acting on a particle placed in the nonuniform
      electric fields of dielectrophoresis devices, such as square cages. We show that
      if the particle size is much smaller than the dielectrophoretic cage size, the PD
      model accurately approximates the actual DEP force, computed numerically using
      the Maxwell stress tensor method. However, when the two sizes are comparable, the
      actual DEP force differs significantly in both magnitude and direction from that
      given by the PD model.

PMID- 16090103
TI  - Strongly nonlinear waves in a chain of Teflon beads.
AB  - One-dimensional "sonic vacuum" type phononic crystals were assembled from a chain
      of polytetrafluoroethylene (PTFE,Teflon) spheres with different diameters in a
      Teflon holder. It was demonstrated that this polymer-based sonic vacuum, with
      exceptionally low elastic modulus of particles, supports propagation of strongly
      nonlinear solitary waves with a very low speed. These solitary waves can be
      described using the classical nonlinear Hertz law despite the viscoelastic nature
      of the polymer and high strain rate deformation of the contact area. The
      experimentally measured speeds of solitary waves at high amplitudes are close to
      the theoretically estimated values with a Young's modulus of 1.46 GPa obtained
      from shock wave experiments. This is significantly higher than the Young's
      modulus of PTFE from ultrasonic measurements. Trains of strongly nonlinear
      solitary waves excited by an impact were investigated experimentally and were
      found to be in reasonable agreement with numerical calculations based on Hertz
      interaction law though exhibiting a significant dissipation.

PMID- 16090104
TI  - Causal determination of acoustic group velocity and frequency derivative of
      attenuation with finite-bandwidth Kramers-Kronig relations.
AB  - Kramers-Kronig (KK) analyses of experimental data are complicated by the
      extrapolation problem, that is, how the unexamined spectral bands impact KK
      calculations. This work demonstrates the causal linkages in resonant-type data
      provided by acoustic KK relations for the group velocity (c(g)) and the
      derivative of the attenuation coefficient (alpha') (components of the derivative
      of the acoustic complex wave number) without extrapolation or unmeasured
      parameters. These relations provide stricter tests of causal consistency relative
      to previously established KK relations for the phase velocity (c(p)) and
      attenuation coefficient (alpha) (components of the undifferentiated acoustic wave
      number) due to their shape invariance with respect to subtraction constants. For
      both the group velocity and attenuation derivative, three forms of the relations
      are derived. These relations are equivalent for bandwidths covering the entire
      infinite spectrum, but differ when restricted to bandlimited spectra. Using
      experimental data from suspensions of elastic spheres in saline, the accuracy of
      finite-bandwidth KK predictions for c(g) and alpha' is demonstrated. Of the
      multiple methods, the most accurate were found to be those whose integrals were
      expressed only in terms of the phase velocity and attenuation coefficient
      themselves, requiring no differentiated quantities.

PMID- 16090105
TI  - Discrete dark solitons with multiple holes.
AB  - We consider staggered dark solitons admitted by the discrete nonlinear
      Schrodinger equation with focusing cubic nonlinearity. In particular, we focus on
      the study of dark solitons with several holes characterized by the number of
      zeros in the uncoupled case. Such structures reveal interesting behaviors, such
      as stable intersite dark solitons. All of the structures have no counterpart in
      the strong coupling limit since they disappear in a saddle-node bifurcation. We
      also consider the evolution of structures with multiple holes representing an
      interaction between multiple dark solitons in a very discrete case.

PMID- 16090106
TI  - Stabilizing the discrete vortex of topological charge S=2.
AB  - We study the instability of the discrete vortex with topological charge S=2 in a
      prototypical lattice model and observe its mediation through the central lattice
      site. Motivated by this finding, we analyze the model with the central site being
      inert. We identify analytically and observe numerically the existence of a range
      of linearly stable discrete vortices with S=2 in the latter model. The range of
      stability is comparable to that of the recently observed experimentally S=1
      discrete vortex, suggesting the potential for observation of such higher charge
      discrete vortices.

PMID- 16090107
TI  - Numerical simulations of negative-index refraction in wedge-shaped metamaterials.
AB  - A wedge-shaped structure made of split-ring resonators (SRR) and wires is
      numerically simulated to evaluate its refraction behavior. Four frequency bands,
      namely, the stop band, left-handed band, ultralow-index band, and positive-index
      band, are distinguished according to the refracted field distributions. Negative
      phase velocity inside the wedge is demonstrated in the left-handed band and the
      Snell's Law is conformed in terms of its refraction behaviors in different
      frequency bands. Our results confirmed that negative index of refraction indeed
      exists in such a composite metamaterial and also provided a convincing support to
      the results of previous Snell's Law experiments.

PMID- 16090108
TI  - Full transmission through perfect-conductor subwavelength hole arrays.
AB  - Light transmission through 2D subwavelength hole arrays in perfect-conductor
      films is shown to be complete (100%) at some resonant wavelengths even for
      arbitrarily narrow holes. Conversely, the reflection on a 2D planar array of
      nonabsorbing scatterers is shown to be complete at some wavelengths regardless
      how small the scatterers are. These results are proven analytically and
      corroborated by rigorous numerical solution of Maxwell's equations. This work
      supports the central role played by dynamical diffraction during light
      transmission through subwavelength hole arrays and it provides a systematics to
      analyze more complex geometries and many of the features observed in connection
      with transmission through hole arrays.

PMID- 16090109
TI  - Self-similar parabolic beam generation and propagation.
AB  - The (1+1) -dimensional and (2+1) -dimensional amplified nonlinear Schrodinger
      equations incorporating diffraction, Kerr nonlinearity, and gain are solved
      analytically and numerically. An asymptotic solution is found corresponding to
      self-similar propagation of a beam with parabolic amplitude and phase profiles.
      While the (1+1) -dimensional solution is directly analogous to parabolic pulse
      propagation in nonlinear dispersive media, the existence of self-similar
      propagation in (2+1) dimensions is a nontrivial question, given that spatial
      solitons are unstable in bulk media with nonsaturating nonlinearities. We show
      that self-similar parabolic beams are possible in such media with gain and a
      negative nonlinear index.

PMID- 16090110
TI  - Analytical approach to soliton ratchets in asymmetric potentials.
AB  - We use soliton perturbation theory and collective coordinate ansatz to
      investigate the mechanism of soliton ratchets in a driven and damped asymmetric
      double sine-Gordon equation. We show that, at the second order of the
      perturbation scheme, the soliton internal vibrations can couple effectively, in
      presence of damping, to the motion of the center of mass, giving rise to
      transport. An analytical expression for the mean velocity of the soliton is
      derived. The results of our analysis confirm the internal mode mechanism of
      soliton ratchets proposed in [Phys. Rev. E 65, 025602(R) (2002)].

PMID- 16090111
TI  - Semiclassical model of stimulated Raman scattering in photonic crystals.
AB  - We study the stimulated Raman scattering (SRS) of light from an atomic system
      embedded in a photonic crystal and coherently pumped by a laser field. In our
      study, the electromagnetic field is treated classically and the atomic system is
      described quantum mechanically. Considering a decomposition of the pump and
      Stokes fields into the Bloch modes of the photonic crystals and using a
      multiscale analysis, we derive the Maxwell-Bloch equations for SRS in photonic
      crystals. These equations contain effective parameters that characterize the SRS
      gain, the nonlinear atomic response to the electromagnetic field, and the group
      velocity and that can be calculated in terms of the Bloch modes of the
      unperturbed photonic crystal. We show that if the pump laser frequency is tuned
      near a photonic band edge and the atomic system is carefully chosen such that the
      Stokes mode matches another photonic band edge, low-threshold, enhanced Raman
      amplification is possible. Possible physical realizations of SRS in photonic
      crystals are also discussed.

PMID- 16090112
TI  - Ratchet behavior in nonlinear Klein-Gordon systems with pointlike
      inhomogeneities.
AB  - We investigate the ratchet dynamics of nonlinear Klein-Gordon kinks in a
      periodic, asymmetric lattice of pointlike inhomogeneities. We explain the
      underlying rectification mechanism within a collective coordinate framework,
      which shows that such a system behaves as a rocking ratchet for point particles.
      Careful attention is given to the kink width dynamics and its role in the
      transport. We also analyze the robustness of our kink rocking ratchet in the
      presence of noise. We show that the noise activates unidirectional motion in a
      parameter range where such motion is not observed in the noiseless case. This is
      subsequently corroborated by the collective variable theory. An explanation for
      this phenomenon is given.

PMID- 16090113
TI  - Spectral representation of the effective dielectric constant of graded
      composites.
AB  - We generalize the Bergman-Milton spectral representation, originally derived for
      a two-component composite, to extract the spectral density function for the
      effective dielectric constant of a graded composite. This work has been motivated
      by a recent study of the optical absorption spectrum of a graded metallic film
      [Huang and Yu, Appl. Phys. Lett. 85, 94 (2004)] in which a broad surface-plasmon
      absorption band was shown to be responsible for enhanced nonlinear optical
      response and an attractive figure of merit. It turns out that, unlike in the case
      of homogeneous constituent components, the characteristic function of a graded
      composite is a continuous function because of the continuous variation of the
      dielectric function within the constituent components. Analytical generalization
      to three-dimensional graded composites is discussed, and numerical calculations
      for multilayer composites are given as a simple application.

PMID- 16090114
TI  - Coupled-mode theory for photonic band-gap inhibition of spatial instabilities.
AB  - We study the inhibition of pattern formation in nonlinear optical systems using
      intracavity photonic crystals. We consider mean-field models for singly and
      doubly degenerate optical parametric oscillators. Analytical expressions for the
      new (higher) modulational thresholds and the size of the "band gap" as a function
      of the system and photonic crystal parameters are obtained via a coupled-mode
      theory. Then, by means of a nonlinear analysis, we derive amplitude equations for
      the unstable modes and find the stationary solutions above threshold. The form of
      the unstable mode is different in the lower and upper parts of the band gap. In
      each part there is bistability between two spatially shifted patterns. In large
      systems stable wall defects between the two solutions are formed and we provide
      analytical expressions for their shape. The analytical results are favorably
      compared with results obtained from the full system equations. Inhibition of
      pattern formation can be used to spatially control signal generation in the
      transverse plane.

PMID- 16090115
TI  - Oscillations of dark solitons in trapped Bose-Einstein condensates.
AB  - We consider a one-dimensional defocusing Gross-Pitaevskii equation with a
      parabolic potential. Dark solitons oscillate near a center of the potential trap
      and their amplitude decays due to radiative losses (sound emission). We develop a
      systematic asymptotic multiscale expansion method in the limit when the potential
      trap is flat. The first-order approximation predicts a uniform frequency of
      oscillations for the dark soliton of arbitrary amplitude. The second-order
      approximation predicts the nonlinear growth rate of the oscillation amplitude,
      which results in decay of the dark soliton. The results are compared with
      previous publications and numerical computations.

PMID- 16090116
TI  - Soliton interaction in a fiber ring laser.
AB  - We have experimentally investigated the soliton interaction in a passively mode
      locked fiber ring laser and revealed the existence of three types of strong
      soliton interaction: a global type of soliton interaction caused by the existence
      of unstable cw components, a local type of soliton interaction mediated through
      the radiative dispersive waves, and the direct soliton interaction. We found that
      the appearance of the various soliton operation modes observed in the passively
      mode-locked fiber soliton lasers are the direct consequences of these three types
      of soliton interactions. The soliton interaction in the laser is further
      numerically simulated based on a pulse tracing technique. The numerical
      simulations confirmed the existence of the dispersive-wave-mediated soliton
      interaction and the direct soliton interaction. Furthermore, it was shown that
      the resonant dispersive-wave-mediated soliton interaction in the laser always has
      the consequence of causing random irregular relative soliton movement and the
      experimentally observed states of bound solitons are caused by the direct soliton
      interaction. In particular, as the solitons generated in the laser could have a
      profile with long tails, the direct soliton interaction could extend to a soliton
      separation that is larger than 5 times the soliton pulse width.

PMID- 16090117
TI  - Dynamics of ultraslow optical solitons in a cold three-state atomic system.
AB  - We present a systematic study on the dynamics of a ultraslow optical soliton in a
      cold, highly resonant three-state atomic system under Raman excitation. Using a
      method of multiple scales we derive a modified nonlinear Schrodinger equation
      with high-order corrections that describe effects of linear and differential
      absorption, nonlinear dispersion, delay response of nonlinear refractive index,
      diffraction, and third-order dispersion. Taking these effects as perturbations we
      investigate in detail the evolution of the ultraslow optical soliton using a
      standard soliton perturbation theory. We show that due to these high-order
      corrections the ultraslow optical soliton undergoes deformation, change of
      propagating velocity, and shift of oscillating frequency. In addition, a small
      radiation superposed by dispersive waves is also generated from the soliton. The
      results of the present work may provide a guidance that is useful for
      experimental demonstration of ultraslow optical soliton in cold atomic systems.

PMID- 16090118
TI  - Stability and transient effects in nanosecond ultraviolet light filaments in air.
AB  - We investigate the transient behavior and stability of nanosecond duration
      ultraviolet pulses propagating in air. Both the transient behavior arising from
      the finite pulse duration and the modulational instability, are found to cause
      pulses to fragment over lengths on the scale of meters. We discuss the
      theoretical and experimental implications of the instability and transient
      effects for long duration pulse propagating in air and generating filaments. In
      particular, our results imply that continuous-wave models are very limited when
      used to predict dynamical properties of pulse propagation.

PMID- 16090119
TI  - Theory of generation of new frequencies by mixing of solitons and dispersive
      waves in optical fibers.
AB  - We develop a theory of the generation of new spectral components in optical
      fibers pumped with a solitonic pulse and a weak continuous wave (cw). We derive
      the wave number matching conditions for the above process and present an
      analytical method of finding the amplitudes of the generated waves. We discuss
      related effects of the depletion of the cw pump and spectral recoil on the
      soliton. We also point out examples of the generation of supercontinuum spectra
      in fibers, where mixing between solitons and dispersive waves plays an important
      role.

PMID- 16090120
TI  - Finite amplitude elastic waves propagating in compressible solids.
AB  - The paper studies the interaction of a longitudinal wave with transverse waves in
      general isotropic and unconstrained hyperelastic materials, including the
      possibility of dissipation. The dissipative term chosen is similar to the
      classical stress tensor describing a Stokesian fluid and is commonly used in
      nonlinear acoustics. The aim of this research is to derive the corresponding
      general equations of motion, valid for any possible form of the strain energy
      function and to investigate the possibility of obtaining some general and exact
      solutions to these equations by reducing them to a set of ordinary differential
      equations. Then the reductions can lead to some exact closed-form solutions for
      special classes of materials (here the examples of the Hadamard, Blatz-Ko, and
      power-law strain energy densities are considered, as well as fourth-order
      elasticity). The solutions derived are in a time-space separable form and may be
      interpreted as generalized oscillatory shearing motions and generalized
      sinusoidal standing waves. By means of standard methods of dynamical systems
      theory, some peculiar properties of waves propagating in compressible materials
      are uncovered, such as for example, the emergence of destabilizing effects. These
      latter features exist for highly nonlinear strain energy functions such as the
      relatively simple power-law strain energy, but they cannot exist in the framework
      of fourth-order elasticity.

PMID- 16090121
TI  - Regimes of feedback-controlled beam coupling.
AB  - The introduction of certain electronic feedback loops into photorefractive wave
      coupling schemes makes them noise free and leads to dramatic changes of the whole
      nonlinear behavior. The familiar steady states can be transformed into periodic
      states that are characterized by ultimately high and low values of the
      diffraction efficiency eta of the recorded index grating or into quasisteady
      states with small values of eta. These transformations possess thresholds with
      respect to controllable experimental parameters like the coupling strength and
      the input intensity ratio. We present a general analysis of the threshold
      behavior for different modes of the feedback operation and different types of the
      nonlinear photorefractive response. The results obtained (analytical and
      numerical) allow one to predict the regions of stability for feedback-controlled
      steady states and the observable characteristics of the system, including the
      output amplitudes and diffraction efficiency of the spatial grating, beyond these
      regions. They extend strongly the potentialities of the feedback-controlled wave
      coupling.

PMID- 16090122
TI  - Self-similar evolutions of parabolic, Hermite-Gaussian, and hybrid optical
      pulses: Universality and diversity.
AB  - Three novel types of self-similar solutions, termed parabolic, Hermite-Gaussian,
      and hybrid pulses, of the generalized nonlinear Schrodinger equation with varying
      dispersion, nonlinearity, and gain or absorption are obtained. The properties of
      the self-similar evolutions in various nonlinear media are confirmed by numerical
      simulations. Despite the diversity of their formations, these self-similar pulses
      exhibit many universal features which can facilitate significantly the
      achievement of well-defined linearly chirped output pulses from an optical fiber,
      an amplifier, or an absorption medium, under certain parametric conditions. The
      other intrinsic characteristics of each type of self-similar pulses are also
      discussed.

PMID- 16090123
TI  - Achieving transparency with plasmonic and metamaterial coatings.
AB  - The possibility of using plasmonic and metamaterial covers to drastically reduce
      the total scattering cross section of spherical and cylindrical objects is
      discussed. While it is intuitively expected that increasing the physical size of
      an object may lead to an increase in its overall scattering cross section, here
      we see how a proper design of these lossless metamaterial covers near their
      plasma resonance may induce a dramatic drop in the scattering cross section,
      making these objects nearly "invisible" or "transparent" to an outside observer-
      a phenomenon with obvious applications for low-observability and noninvasive
      probe design. Physical insights into this phenomenon and some numerical results
      are provided.

PMID- 16090124
TI  - Gap solitons in a medium with third-harmonic generation.
AB  - We find two-component optical solitons in a nonlinear waveguide with a Bragg
      grating, including Kerr effects and third-harmonic generation (THG). The model
      may be realized in temporal and in spatial domains. Two species of fundamental
      gap solitons (GSs) are found. The first ("THG-gap soliton") has the bulk of its
      energy at the fundamental frequency (FF) and a lesser part in the third-harmonic
      (TH) band. The FF part of the soliton is always single humped; the TH part may be
      single or double humped. Stability domains for quiescent and moving THG-gap
      solitons strongly shrink with increase of velocity. The second species is the
      usual ("simple") GS, sitting entirely in the TH band. More complex solutions are
      also found, in the form of a bound state of a THG-gap soliton and two simple GSs,
      with a finite binding energy. When a THG-gap soliton is unstable, the instability
      is oscillatory. It may ultimately cause the THG-gap soliton to throw off some
      radiation and evolve into a localized structure with the FF and TH components out
      of phase, with or without internal oscillations. Stable solitons feature an
      excited state (i.e., they support a localized eigenmode).

PMID- 16090125
TI  - Experimental and theoretical study of processes leading to steady-state sound in
      annular thermoacoustic engines.
AB  - This paper gives a simplified analytical description of spontaneous generation
      and finite amplitude saturation of sound in annular thermoacoustic engines, and
      also provides comparison with experiments. The model includes the precise
      description of thermoacoustic amplification of sound (induced by interaction
      between an heterogeneously heated stack of solid plates and resonant gas
      oscillations), which accounts for the details of the temperature distribution in
      the whole thermoacoustic device (i.e., which does not only account for the mean
      temperature gradient along the stack). The saturation of the acoustic wave
      amplitude is described by taking into account both the reverse influence of high
      amplitude acoustic field on temperature field, and the dissipation of acoustic
      energy due to higher harmonics generation and minor losses (vortex generation).
      From the comparison between simulation results and experiments, it is
      demonstrated that the dynamical behavior observed in our experimental device is
      predominantly controlled by the effects of acoustic streaming and acoustically
      enhanced thermal conductivity tending not only to reduce the externally imposed
      temperature gradient along the stack, but also to change the shape of the
      temperature field.

PMID- 16090126
TI  - Nonlinear propagation of electromagnetic waves in negative-refraction-index
      composite materials.
AB  - We investigate the nonlinear propagation of electromagnetic waves in left-handed
      materials. For this purpose, we consider a set of coupled nonlinear Schrodinger
      (CNLS) equations, which govern the dynamics of coupled electric and magnetic
      field envelopes. The CNLS equations are used to obtain a nonlinear dispersion,
      which depicts the modulational stability profile of the coupled plane-wave
      solutions in left-handed materials. An exact (in)stability criterion for
      modulational interactions is derived, and analytical expressions for the
      instability growth rate are obtained.

PMID- 16090127
TI  - Acoustical impedance defined by wave-function solutions of the reduced Webster
      equation.
AB  - The electrical impedance was first defined by Heaviside in 1884, and the analogy
      of the acoustical impedance was made by Webster in 1919. However, it can be shown
      that Webster did not draw a full analogy with the electromagnetic potential, the
      potential energy per unit charge. This paper shows that the analogous "acoustical
      potential" the potential energy per unit displacement of fluid, corresponds to
      the wave function Psi of the reduced Webster equation, which is of Klein-Gordon
      form. The wave function is found to obey all of Dirichlet, Von Neumann, and mixed
      (Robins) boundary conditions, and the latter give rise to resonance phenomena
      that are not elucidated by Webster's analysis. It is shown that the exact
      Heaviside analogy yields a complete analytic account of the one-dimensional input
      impedance, that accounts for both plane- and dispersive-wave propagation both at
      the origin and throughout the duct.

PMID- 16090128
TI  - Dynamic regimes of fluids simulated by multiparticle-collision dynamics.
AB  - We investigate the hydrodynamic properties of a fluid simulated with a mesoscopic
      solvent model. Two distinct regimes are identified, the "particle regime" in
      which the dynamics is gaslike and the "collective regime" where the dynamics is
      fluidlike. This behavior can be characterized by the Schmidt number, which
      measures the ratio between viscous and diffusive transport. Analytical
      expressions for the tracer diffusion coefficient, which have been derived on the
      basis of a molecular-chaos assumption, are found to describe the simulation data
      very well in the particle regime, but important deviations are found in the
      collective regime. These deviations are due to hydrodynamic correlations. The
      model is then extended in order to investigate self-diffusion in colloidal
      dispersions. We study first the transport properties of heavy pointlike particles
      in the mesoscopic solvent, as a function of their mass and number density.
      Second, we introduce excluded-volume interactions among the colloidal particles
      and determine the dependence of the diffusion coefficient on the colloidal volume
      fraction for different solvent mean-free paths. In the collective regime, the
      results are found to be in good agreement with previous theoretical predictions
      based on Stokes hydrodynamics and the Smoluchowski equation.

PMID- 16090129
TI  - Continuous extremal optimization for Lennard-Jones clusters.
AB  - We explore a general-purpose heuristic algorithm for finding high-quality
      solutions to continuous optimization problems. The method, called continuous
      extremal optimization (CEO), can be considered as an extension of extremal
      optimization and consists of two components, one which is responsible for global
      searching and the other which is responsible for local searching. The CEO's
      performance proves competitive with some more elaborate stochastic optimization
      procedures such as simulated annealing, genetic algorithms, and so on. We
      demonstrate it on a well-known continuous optimization problem: the Lennard-Jones
      cluster optimization problem.

PMID- 16090130
TI  - Thermal boundary condition for the thermal lattice Boltzmann equation.
AB  - A thermal boundary condition for a double-population thermal lattice Boltzmann
      equation (TLBE) is introduced and numerically demonstrated. The unknown
      distribution population at the boundary node is decomposed into its equilibrium
      part and nonequilibrium parts, and then the nonequilibrium part is approximated
      with a first-order extrapolation of the nonequilibrium part of the populations at
      the neighboring fluid nodes. Numerical tests with Dirichlet and Neumann boundary
      constraints show that the numerical results of the TLBE together with the present
      boundary schemes agree well with the analytical solutions and those of the finite
      volume method.

PMID- 16090131
TI  - Growth algorithm for finding low energy configurations of simple lattice
      proteins.
AB  - PERM and its new variant nPERMis have been developed to optimize the energy
      function of protein folding based on HP simple lattice model and were found to
      outperform all other previous fully blind general purpose algorithms. Using the
      concept of core-guiding and life-forecasting, we propose a new version of
      nPERMis, called nPERMh. A major difference with respect to nPERMis is that
      criteria for further growth of new residue are based on the species of current
      growing monomer and its position in the HP sequence. Seventeen sequences of
      length ranging from 46 to 124 residues were tested by nPERMh on the cubic lattice
      and our algorithm proved very efficient. It should be pointed out that our new
      version of nPERMis is exclusively designed for conformational search. We hope
      that similar methods will ultimately be useful for finding native states of more
      realistic protein models.

PMID- 16090132
TI  - Hybrid method coupling molecular dynamics and Monte Carlo simulations to study
      the properties of gases in microchannels and nanochannels.
AB  - We combine molecular dynamics (MD) and Monte Carlo (MC) simulations to study the
      properties of gas molecules confined between two hard walls of a microchannel or
      nanochannel. The coupling between MD and MC simulations is introduced by
      performing MD near the boundaries for accuracy and MC in the bulk because of the
      low computational cost. We characterize the influence of different densities and
      molecule sizes on the equilibrium properties of the gas in the microchannel. The
      effect of the particle size on the simulation results is very small in the case
      of a dilute gas and increases with the density. The hybrid MD-MC simulation
      method is validated by comparing the results for density and temperature profiles
      with those of pure MD and pure MC simulations. These results compare well for
      pure MD and pure MC, as well as hybrid MD-MC, both in the bulk and near the
      boundaries, when hard-sphere interactions are used. When Lennard-Jones potentials
      are used to accurately model the interactions between the gas and wall molecules
      instead, the results of pure MD simulations differ significantly from the pure MC
      simulations near the boundaries, but the results of the hybrid method compare
      well with the pure MD results near the wall, and with the pure MC and pure MD
      results in the middle of the channel. The hybrid method also very accurately
      simulates the interface between the MD and MC simulation domains. Comparisons
      between MD, MC, and hybrid MD-MC computational costs are outlined. The speedup
      when using 50% of the domain for MD simulations and 50% for MC simulations is
      very small compared to pure MD simulations times, but this speedup increases
      drastically for more realistic situations where the region near the wall is small
      compared to the bulk region.

PMID- 16090133
TI  - Domain-decomposition method for parallel lattice Boltzmann simulation of
      incompressible flow in porous media.
AB  - The lattice Boltzmann method has proven to be a promising method to simulate flow
      in porous media. Its practical application often relies on parallel computation
      because of the demand for a large domain and fine grid resolution to adequately
      resolve pore heterogeneity. The existing domain-decomposition methods for
      parallel computation usually decompose a domain into a number of subdomains first
      and then recover the interfaces and perform the load balance. Normally, the
      interface recovery and the load balance have to be performed iteratively until an
      acceptable load balance is achieved; this costs time. In this paper we propose a
      cell-based domain-decomposition method for parallel lattice Boltzmann simulation
      of flow in porous media. Unlike the existing methods, the cell-based method
      performs the load balance first to divide the total number of fluid cells into a
      number of groups (or subdomains), in which the difference of fluid cells in each
      group is either 0 or 1, depending on if the total number of fluid cells is a
      multiple of the processor numbers; the interfaces between the subdomains are
      recovered at last. The cell-based method is to recover the interfaces rather than
      the load balance; it does not need iteration and gives an exact load balance. The
      performance of the proposed method is analyzed and compared using different
      computer systems; the results indicate that it reaches the theoretical parallel
      efficiency. The method is then applied to simulate flow in a three-dimensional
      porous medium obtained with microfocus x-ray computed tomography to calculate the
      permeability, and the result shows good agreement with the experimental data.

PMID- 16090134
TI  - Self-referred approach to lacunarity.
AB  - This paper describes an approach to lacunarity which adopts the pattern under
      analysis as the reference for the sliding window procedure. The superiority of
      such a scheme with respect to more traditional methodologies, especially when
      dealing with finite-size objects, is established and illustrated through
      applications to diffusion limited aggregation pattern characterization. It is
      also shown that, given the enhanced accuracy and sensitivity of this scheme, the
      shape of the window becomes an important parameter, with advantage for circular
      windows.

PMID- 16090135
TI  - Most stable structure for hard spheres.
AB  - The hard sphere model is known to show a liquid-solid phase transition, with the
      solid expected to be either face centered cubic or hexagonal close packed. The
      differences in free energy of the two structures are very small and various
      attempts have been made to determine which structure is the more stable. We
      contrast the different approaches and extend one.

PMID- 16090136
TI  - Flow past an impulsively started circular cylinder using a higher-order
      semicompact scheme.
AB  - In the present investigation an attempt has been made to solve the two
      dimensional incompressible viscous flow past an impulsively started circular
      cylinder for Reynolds numbers ranging from 20 to 5000 using higher-order
      semicompact scheme (HOSC). Unlike conventional higher-order compact schemes the
      HOSC scheme has been developed to handle the circular geometry of the chosen
      problem and the intensive algebraic manipulations have been reduced considerably
      by relaxing the compactness of the computational stencil for few terms (but
      retained for most of the terms) of the discretized equations. For the flow past
      an impulsively started circular cylinder the results obtained at low and moderate
      Reynolds numbers have been validated with the experimental and numerical
      observations available in the literature. For high Reynolds number flows, the
      present scheme rightly captures the alpha phenomenon at Re=1000 and both beta and
      alpha phenomena one after the other at Re=5000 .

PMID- 16090137
TI  - Phase separation patterns for diblock copolymers on spherical surfaces: a finite
      volume method.
AB  - We explore phase separation on spherical surfaces by solving the Cahn-Hilliard
      equation modified for diblock copolymers using a finite volume method. The
      spherical surface is discretized into almost uniform triangles by employing
      successive dyadic refinements of the spherical icosahedron, a methodology that
      avoids potential mathematical and numerical problems related to the poles in
      spherical coordinates. The finite volume method is based on averaging Voronoi
      cells built from triangular meshes to calculate the Laplace-Beltrami operator on
      the curved surface, which greatly improves both the accuracy and speed of
      calculation as compared to the conventional finite difference method. By using
      this method we simulate the phase separation of diblock copolymers on a spherical
      surface. It is found that stable and intrinsic defects, which would not occur in
      a flat space after sufficient annealing, appear in the periodic arrangement of
      the domains on the curved surface due to the distinct Euler characteristic of the
      surface.

PMID- 16090138
TI  - Self-referential Monte Carlo method for calculating the free energy of
      crystalline solids.
AB  - A self-referential Monte Carlo method is described for calculating the free
      energy of crystalline solids. All Monte Carlo methods for the free energy of
      classical crystalline solids calculate the free-energy difference between a state
      whose free energy can be calculated relatively easily and the state of interest.
      Previously published methods employ either a simple model crystal, such as the
      Einstein crystal, or a fluid as the reference state. The self-referential method
      employs a radically different reference state; it is the crystalline solid of
      interest but with a different number of unit cells. So it calculates the free
      energy difference between two crystals, differing only in their size. The aim of
      this work is to demonstrate this approach by application to some simple systems,
      namely, the face centered cubic hard sphere and Lennard-Jones crystals. However,
      it can potentially be applied to arbitrary crystals in both bulk and confined
      environments, and ultimately it could also be very efficient.

PMID- 16090139
TI  - Rugged Metropolis sampling with simultaneous updating of two dynamical variables.
AB  - The rugged Metropolis (RM) algorithm is a biased updating scheme which aims at
      directly hitting the most likely configurations in a rugged free-energy
      landscape. Details of the one-variable ( RM1 ) implementation of this algorithm
      are presented. This is followed by an extension to simultaneous updating of two
      dynamical variables ( RM2 ). In a test with the brain peptide Met-Enkephalin in
      vacuum RM2 improves conventional Metropolis simulations by a factor of about 4.
      Correlations between three or more dihedral angles appear to prevent larger
      improvements at low temperatures. We also investigate a multihit Metropolis
      scheme, which spends more CPU time on variables with large autocorrelation times.

PMID- 16090140
TI  - Smoothed particle hydrodynamics model for phase separating fluid mixtures. I.
      General equations.
AB  - We present a thermodynamically consistent discrete fluid particle model for the
      simulation of a recently proposed set of hydrodynamic equations for a phase
      separating van der Waals fluid mixture [P. Espanol and C.A.P. Thieulot, J. Chem.
      Phys. 118, 9109 (2003)]. The discrete model is formulated by following a
      discretization procedure given by the smoothed particle hydrodynamics (SPH)
      method within the thermodynamically consistent general equation for the
      nonequilibrium reversible-irreversible coupling (GENERIC) framework. Each fluid
      particle carries information on the mass, momentum, energy, and the mass fraction
      of the different components. The discrete model allows one to simulate
      nonisothermal dynamic evolution of phase separating fluids with surface tension
      effects while respecting the first and second laws of thermodynamics exactly.

PMID- 16090141
TI  - Smoothed particle hydrodynamics model for phase separating fluid mixtures. II.
      Diffusion in a binary mixture.
AB  - A previously formulated smoothed particle hydrodynamics model for a phase
      separating mixture is tested for the case when viscous processes are negligible
      and only mass and energy diffusive processes take place. We restrict ourselves to
      the case of a binary mixture that can exhibit liquid-liquid phase separation. The
      thermodynamic consistency of the model is assessed and the potential of the model
      to study complex pattern formation in the presence of various thermal boundaries
      is illustrated.

PMID- 16090142
TI  - Monte Carlo algorithms for charged lattice gases.
AB  - We consider Monte Carlo algorithms for the simulation of charged lattice gases
      with purely local dynamics. We study the mobility of particles as a function of
      temperature and show that the poor mobility of particles at low temperatures is
      due to "trails" or "strings" left behind after particle motion. We introduce
      modified updates which substantially improve the efficiency of the algorithm in
      this regime.

PMID- 16090143
TI  - Reaction-diffusion processes on correlated and uncorrelated scale-free networks.
AB  - We compare reaction-diffusion processes of the A+A-->0 type on scale-free
      networks created with either the configuration model or the uncorrelated
      configuration model. We show via simulations that except for the difference in
      the behavior of the two models, different results are observed within the same
      model when the minimum number of connections for a node varies from k(min) =1 to
      k(min) =2 . This difference is attributed to the varying local properties of the
      two systems. In all cases, we are able to identify a power-law behavior of the
      density decay with time, with an exponent f>1 , considerably larger than its
      lattice counterpart.

PMID- 16090144
TI  - Load distribution in weighted complex networks.
AB  - We study the load distribution in weighted networks by measuring the effective
      number of optimal paths passing through a given vertex. The optimal path, along
      which the total cost is minimum, crucially depends on the cost distribution
      function p(c) (c) . In the strong disorder limit, where p(c) (c) approximately c(
      1) , the load distribution follows a power law both in the Erdos-Renyi (ER)
      random graphs and in the scale-free (SF) networks, and its characteristics are
      determined by the structure of the minimum spanning tree. The distribution of
      loads at vertices with a given vertex degree also follows the SF nature similar
      to the whole load distribution, implying that the global transport property is
      not correlated to the local structural information. Finally, we measure the
      effect of disorder by the correlation coefficient between vertex degree and load,
      finding that it is larger for ER networks than for SF networks.

PMID- 16090145
TI  - Nonlocal evolution of weighted scale-free networks.
AB  - We introduce the notion of globally updating evolution for a class of weighted
      networks, in which the weight of a link is characterized by the amount of data
      packet transport flowing through it. By noting that the packet transport over the
      network is determined nonlocally, this approach can explain the generic nonlinear
      scaling between the strength and the degree of a node. We demonstrate by a simple
      model that the strength-driven evolution scheme recently introduced can be
      generalized to a nonlinear preferential attachment rule, generating the power-law
      behaviors in degree and in strength simultaneously.

PMID- 16090146
TI  - Simple algorithm to test for linking to Wilson loops in percolation.
AB  - A simple burning or epidemic type of algorithm is developed in order to test
      whether any loops in percolation clusters link a fixed reference loop, a problem
      considered recently by Gliozzi in the context of gauge theory. We test our
      algorithm at criticality in both two dimensions, where the behavior agrees with a
      theoretical prediction, and in three dimensions.

PMID- 16090147
TI  - Simple sandpile model of active-absorbing state transitions.
AB  - We study a simple sandpile model of active-absorbing state transitions in which a
      particle can hop out of a site only if the number of particles at that site is
      above a certain threshold. We show that the active phase has product measure
      whereas nontrivial correlations are found numerically in the absorbing phase. It
      is argued that the system relaxes to the latter phase slower than exponentially.
      The critical behavior of this model is found to be different from that of the
      other known universality classes.

PMID- 16090148
TI  - Slow phase relaxation as a route to quantum computing beyond the quantum chaos
      border.
AB  - We reveal that phase memory can be much longer than energy relaxation in systems
      with exponentially large dimensions of Hilbert space; this finding is documented
      by 50 years of nuclear experiments, though the information is somewhat hidden.
      For quantum computers Hilbert spaces of dimension 2(100) or larger will be
      typical and therefore this effect may contribute significantly to reduce the
      problems of scaling of quantum computers to a useful number of qubits.

PMID- 16090149
TI  - Generalized dimensions for fluctuations in the solar wind.
AB  - We analyze time series of velocities of the solar wind plasma including the
      outward-directed component of Alfvenic turbulence within slow wind observed by
      the Helios 2 spacecraft in the inner heliosphere. We demonstrate that the
      influence of noise in the data can be efficiently reduced by a singular-value
      decomposition filter. The resulting generalized dimensions show a multifractal
      structure of the solar wind attractor in the inner heliosphere. The obtained
      multifractal spectrum is consistent with that for the multifractal measure on the
      self-similar weighted baker's map with two parameters describing uniform
      compression and natural invariant measure on the attractor of the system.

PMID- 16090150
TI  - Drag reduction by polymer additives in decaying turbulence.
AB  - We present results from a systematic numerical study of decaying turbulence in a
      dilute polymer solution by using a shell-model version of the finitely extensible
      nonlinear elastic and Peterlin equations. Our study leads to an appealing
      definition of the drag reduction for the case of decaying turbulence. We exhibit
      several new results, such as the potential-energy spectrum of the polymer,
      hitherto unobserved features in the temporal evolution of the kinetic-energy
      spectrum, and characterize intermittency in such systems. We compare our results
      with the Gledzer-Ohkitani-Yamada shell model for fluid turbulence.

PMID- 16090151
TI  - Analytic solutions to the shallow water equations.
AB  - Analytic, two-dimensional steady-state solutions to the rotating shallow water
      equations over variable topography are derived, by exploiting a drastic
      simplification of the equilibrium problem that occurs for nondivergent flows. For
      such flows, the equilibrium system decouples, and the cross-stream component of
      the momentum equation formally reduces to the barotropic vorticity equation.
      Thus, any solution to the barotropic vorticity equation can be used, in
      principle, to construct exact equilibrium solutions to the shallow water
      equations.

PMID- 16090152
TI  - Photonic band gap effects on spontaneous emission lifetimes of an assembly of
      atoms in two-dimensional photonic crystals.
AB  - The lifetime distribution functions of the spontaneous emission (SE) of the
      excited atoms embedded in two-dimensional (2D) photonic crystals (PCs) with
      square lattice, consisting of square air rods in dielectric medium with different
      filling factors, are calculated by using the plane wave expansion method. The
      numerical results show that the SE in the 2D PCs cannot be prohibited completely
      but it can be inhibited intensively by the pseudo-PBG of the PCs. In the
      pseudoband edges, the SE is accelerated obviously. The reduced average lifetime
      of the excited atoms and the extension of the reduced lifetime distribution in
      the 2D PCs both are the same as those in the 3D PCs in the order of magnitude.
      Our results provide an available way to control the behavior of the SE by
      changing the structures of the 2D PCs.

PMID- 16090153
TI  - Generalized discretization of the Kardar-Parisi-Zhang equation.
AB  - We report the generalized spatial discretization of the Kardar-Parisi-Zhang (KPZ)
      equation in 1+1 dimensions. We solve exactly the steady state probability density
      function for the discrete heights of the interface, for any discretization
      scheme. We show that the discretization prescription is a consequence of each
      particular model. We derive the discretization prescription of the KPZ equation
      for the ballistic deposition model.

PMID- 16090154
TI  - Structural phase transitions of vortex matter in an optical lattice.
AB  - We consider the vortex structure of a rapidly rotating trapped atomic Bose
      Einstein condensate in the presence of a corotating periodic optical lattice
      potential. We observe a rich variety of structural phases which reflect the
      interplay of the vortex-vortex and vortex-lattice interactions. The lattice
      structure is very sensitive to the ratio of vortices to pinning sites and we
      observe structural phase transitions and domain formation as this ratio is
      varied.

PMID- 16090155
TI  - Complex chemical potential: signature of decay in a bose-einstein condensate.
AB  - We explore the zero-temperature statics of an atomic Bose-Einstein condensate in
      which a Feshbach resonance creates a coupling to a second condensate component of
      quasibound molecules. Using a variational procedure to find the equation of
      state, the appearance of this binding is manifest in a collapsing ground state,
      where only the molecular condensate is present up to some critical density.
      Further, an excited state is seen to reproduce the usual low-density atomic
      condensate behavior in this system, but the molecular component is found to
      produce a coherent, many-body decay, quantified by the imaginary part of the
      chemical potential. Most importantly, the unique decay rate dependencies on
      density (approximately rho (3/2)) and on scattering length (approximately (5/2))
      can be measured in experimental tests of this result.

PMID- 16090156
TI  - Optically induced polarons in bose-einstein condensates: monitoring composite
      quasiparticle decay.
AB  - Nonresonant light scattering off atomic Bose-Einstein condensates is predicted to
      give rise to hitherto unexplored composite quasiparticles: unstable polarons,
      i.e., local "impurities" dressed by virtual phonons. Optical monitoring of their
      spontaneous decay can display either Zeno or anti-Zeno deviations from the golden
      rule, and thereby probe the temporal correlations of elementary excitations in
      the condensates.

PMID- 16090157
TI  - Proposal for quantum gates in permanently coupled antiferromagnetic spin rings
      without need of local fields.
AB  - We propose a scheme for the implementation of quantum gates which is based on the
      qubit encoding in antiferromagnetic molecular rings. We show that a proper
      engineering of the intercluster link would result in an effective coupling that
      vanishes as far as the system is kept in the computational space, while it is
      turned on by a selective excitation of specific auxiliary states. These are also
      shown to allow the performing of single-qubit and two-qubit gates without an
      individual addressing of the rings by means of local magnetic fields.

PMID- 16090158
TI  - Microscopic entropy of the black ring.
AB  - A surprising new seven-parameter supersymmetric black ring solution of five
      dimensional supergravity has recently been discovered. In this paper, M theory is
      used to give an exact microscopic accounting of its entropy.

PMID- 16090159
TI  - Infrared Lorentz violation and slowly instantaneous electricity.
AB  - We study a modification of electromagnetism which violates Lorentz invariance at
      large distances. In this theory, electromagnetic waves are massive, but the
      static force between charged particles is Coulomb, not Yukawa. At very short
      distances the theory looks just like QED. But for distances larger than 1/m the
      massive dispersion relation of the waves can be appreciated, and the Coulomb
      force can be used to communicate faster than the speed of light. In fact,
      electrical signals are transmitted instantly, but take a time approximately 1/m
      to build up to full strength. After that, undamped oscillations of the electric
      field are set in and continue until they are dispersed by the arrival of the
      Lorentz-obeying part of the transmission. Experimental constraints imply that the
      Compton wavelength of the photon may be as small as 6000 km. This bound is weaker
      than for a Lorentz-invariant mass, essentially because the Coulomb constraint is
      removed.

PMID- 16090160
TI  - Improved measurement of the form factors in the decay lambda+c-->lambda + nue.
AB  - Using the CLEO detector at the Cornell Electron Storage Ring, we have studied the
      distribution of kinematic variables in the decay lambda(+)(c)lambda--> e(+)nu(e).
      By performing a four-dimensional maximum likelihood fit, we determine the form
      factor ratio, R= f(2)/f(1) = -0.31 +/- 0.05(stat) +/- 0.04(syst), the pole mass,
      M(pole) = [2.21 +/- 0.08(stat) +/- 0.14(syst)] GeV/c(2), and the decay asymmetry
      parameter of the lambda(+)(c), alpha (lambda(c)) = -0.86 +/-0.03(stat) +/-
      0.02(syst), for q(2) = 0.67 (GeV/c(2))(2). We compare the angular distributions
      of the lambda(+)(c) and lambda(-)(c) and find no evidence for CP violation:
      A(lambda(c)) = (alpha(lambda(c)) + alpha (lambda(c)))/(alpha(lambda(c))
      alpha(lambda(c))) = 0.00 +/- 0.03(stat) +/- 0.01(syst) +/- 0.02, where the third
      error is from the uncertainty in the world average of the CP-violating parameter,
      A(lambda), for ppi(-).

PMID- 16090162
TI  - Collider phenomenology of the Higgsless models.
AB  - We identify and study the signatures of the recently proposed Higgsless models at
      the CERN Large Hadron Collider (LHC). We concentrate on tests of the mechanism of
      partial unitarity restoration in the longitudinal vector boson scattering, which
      is crucial to the phenomenological success of any Higgsless model and does not
      depend on the model-building details. We investigate the discovery reach for
      charged massive vector boson resonances and show that all of the preferred
      parameter space will be probed with 100 fb(-1) of LHC data. Unitarity restoration
      requires that the masses and couplings of the resonances obey certain sum rules.
      We discuss the prospects for their experimental verification at the LHC.

PMID- 16090163
TI  - Study for the pentaquark potential in SU(3) lattice QCD.
AB  - We perform the first study of the static pentaquark (5Q) potential V(5Q) in SU(3)
      quenched lattice QCD with 16(3) x 32 and beta = 6.0. From the 5Q Wilson loop,
      V(5Q) is calculated in a gauge-invariant manner, with the smearing method to
      enhance the ground-state component. V(5Q) is well described by the OGE-plus-multi
      Y ansatz: a sum of the one-gluon-exchange (OGE) Coulomb term and the multi-Y-type
      linear term proportional to the minimal total length of the flux tube linking the
      five quarks. Comparing with QQ and3Q potentials, we find a universality of the
      string tension, sigma(QQ) approximately sigma(3Q) approximately sigma(5Q), and
      the OGE result for Coulomb coefficients.

PMID- 16090165
TI  - Quasielastic 3He(e,e'p)2H reaction at Q2 = 1.5 GeV2 for recoil momenta up to 1
      GeV/c.
AB  - We have studied the quasielastic 3He(e,e(')p)2H reaction in perpendicular
      coplanar kinematics, with the energy and the momentum transferred by the electron
      fixed at 840 MeV and 1502 MeV/c, respectively. The 3He(e,e(')p)2H cross section
      was measured for missing momenta up to 1000 MeV/c, while the A(TL) asymmetry was
      extracted for missing momenta up to 660 MeV/c. For missing momenta up to 150
      MeV/c, the cross section is described by variational calculations using modern
      3He wave functions. For missing momenta from 150 to 750 MeV/c, strong final-state
      interaction effects are observed. Near 1000 MeV/c, the experimental cross section
      is more than an order of magnitude larger than predicted by available theories.
      The A(TL) asymmetry displays characteristic features of broken factorization with
      a structure that is similar to that generated by available models.

PMID- 16090164
TI  - Omega- and Omega+ production in central Pb + Pb collisions at 40 and 158A GeV.
AB  - Results are presented on Omega production in central Pb+Pb collisions at 40 and
      158A GeV beam energy. For the first time in heavy ion reactions, rapidity
      distributions and total yields were measured for the sum Omega(-) + Omega(+) at
      40A GeV and for Omega(-) and Omega(+) separately at 158A GeV. The yields are
      strongly underpredicted by the string-hadronic UrQMD model but agree better with
      predictions from hadron gas models.

PMID- 16090166
TI  - Observation of in-medium modifications of the omega meson.
AB  - The photoproduction of omega mesons on nuclei has been investigated using the
      Crystal Barrel/TAPS experiment at the ELSA tagged photon facility in Bonn. The
      aim is to study possible in-medium modifications of the omega meson via the
      reaction gamma + A --> omega + X --> pi(0)gamma + X('). Results obtained for Nb
      are compared to a reference measurement on a LH2 target. While for recoiling,
      long-lived mesons (pi(0), eta, and eta;(')), which decay outside of the nucleus,
      a difference in the line shape for the two data samples is not observed, we find
      a significant enhancement towards lower masses for omega mesons produced on the
      Nb target. For momenta less than 500 MeV/c an in-medium omega meson mass of
      M(medium) = [722(+4)(-4)(stat)+35-5(syst)] MeV/c(2) has been deduced at an
      estimated average nuclear density of 0.6rho(0).

PMID- 16090167
TI  - First nuclear moment measurement with radioactive beams by the recoil-in-vacuum
      technique: the g factor of the 2+1 state in 132Te.
AB  - Following Coulomb excitation of the radioactive ion beam (RIB) 132Te at HRIBF we
      report the first use of the recoil-in-vacuum (RIV) method to determine the g
      factor of the 2(+)(1) state: g(973.9 keV 2(+) 132Te) = (+)0.35(5). The advantages
      offered by the RIV method in the context of RIBs and modern detector arrays are
      discussed.

PMID- 16090168
TI  - Creating ground state molecules with optical feshbach resonances in tight traps.
AB  - We propose to create ultracold ground state molecules in an atomic Bose-Einstein
      condensate by adiabatic crossing of an optical Feshbach resonance. We envision a
      scheme where the laser intensity and possibly also frequency are linearly ramped
      over the resonance. Our calculations for (87)Rb show that for sufficiently tight
      traps it is possible to avoid spontaneous emission while retaining adiabaticity,
      and conversion efficiencies of up to 50% can be expected.

PMID- 16090169
TI  - High contrast Ramsey fringes with coherent-population-trapping pulses in a double
      lambda atomic system.
AB  - We report the observation of Raman-Ramsey fringes using a double lambda scheme
      creating coherent population trapping in an atomic ensemble combined with pulsed
      optical radiations. The observation was made in a Cs vapor mixed with N2 buffer
      gas in a closed cell. The double lambda scheme is created with lin perpendicular
      lin polarized laser beams leading to higher contrast than the usual simple lambda
      scheme. The pulsed trapping technique leads to narrow fringe widths scaling as
      1/(2T) with high contrasts which are no longer limited by the saturation effect.
      This technique operates in a different way from the classical Ramsey sequence:
      the signal is done by applying a long trapping pulse to prepare the atomic state
      superposition, and fringe detection is accomplished by optical transmission
      during a short second trapping pulse without any perturbation of the dark state.

PMID- 16090170
TI  - Shedding light on the structure of a photoinduced transient excimer by time
      resolved diffraction.
AB  - Time-resolved single-crystal diffraction performed with synchrotron radiation
      shows that the 53(1) micros phosphorescent state, generated in the crystalline
      phase of trimeric {[3,5-(CF3)(2)Pyrazolate]Cu}(3) molecules by exposure to 355 nm
      of light at 17 K, is due to the formation of an excimer rather than the
      shortening of the intramolecular Cu...Cu distances within the trimeric units, or
      the formation of a continuous chain of interacting molecules. One of the
      intermolecular Cu...Cu distances contracts by 0.56 Angstroms from 4.018(1) to
      3.46(1) Angstroms;, whereas the interplanar spacing of the trimers is reduced by
      0.65 Angstroms; from 3.952(1) to 3.33(1) Angstroms. Density-functional theory
      calculations support the formation of a Cu...Cu bond through the intermetallic
      transfer of a Cu 3d electron to a molecular orbital with a large 4p contribution
      on the reacting Cu atoms.

PMID- 16090171
TI  - Phase-coherent frequency combs in the vacuum ultraviolet via high-harmonic
      generation inside a femtosecond enhancement cavity.
AB  - We demonstrate the generation of phase-coherent frequency combs in the vacuum
      utraviolet spectral region. The output from a mode-locked laser is stabilized to
      a femtosecond enhancement cavity with a gas jet at the intracavity focus. The
      resulting high-peak power of the intracavity pulse enables efficient high
      harmonic generation by utilizing the full repetition rate of the laser. Optical
      heterodyne-based measurements reveal that the coherent frequency comb structure
      of the original laser is fully preserved in the high-harmonic generation process.
      These results open the door for precision frequency metrology at extreme
      ultraviolet wavelengths and permit the efficient generation of phase-coherent
      high-order harmonics using only a standard laser oscillator without active
      amplification of single pulses.

PMID- 16090172
TI  - Phase-sensitive detection of bragg scattering at 1D optical lattices.
AB  - We report on the observation of Bragg scattering at 1D atomic lattices. Cold
      atoms are confined by optical dipole forces at the antinodes of a standing wave
      generated by the two counterpropagating modes of a laser-driven high-finesse ring
      cavity. By heterodyning the Bragg-scattered light with a reference beam, we
      obtain detailed information on phase shifts imparted by the Bragg scattering
      process. Being deep in the Lamb-Dicke regime, the scattered light is not
      broadened by the motion of individual atoms.

PMID- 16090173
TI  - Microwave transmission through a single subwavelength annular aperture in a metal
      plate.
AB  - The resonant transmission of a small annular aperture, with a diameter much
      smaller than the radiation wavelength, in a thin metal plate is studied at
      microwave frequencies. It transpires that such an annular aperture supports
      several resonant guided modes, including those that are not quantized in the
      azimuthal direction. Such modes have resonant frequencies that are largely
      independent of the diameter of the annular aperture, thus being supported by
      annular apertures that tend to zero radius. The transmittance of such a structure
      at microwave frequencies is detailed and compared with the predictions of a
      finite element method model.

PMID- 16090174
TI  - Measurement of harmonic phase differences by interference of attosecond light
      pulses.
AB  - By using a self-referencing technique, we have experimentally measured the
      influence of the carrier-envelope phase of femtosecond light pulses on the phase
      of the electric field of the radiation produced by high-order harmonic
      generation. We show that, in particular experimental conditions, the temporal
      evolution of the electric field of the attosecond pulses, is directly controlled
      by the carrier-envelope phase of the driving pulses.

PMID- 16090175
TI  - Is multiscaling an artifact in the stochastically forced Burgers equation?
AB  - We study turbulence in the one-dimensional Burgers equation with a white-in-time,
      Gaussian random force that has a Fourier-space spectrum approximately 1/k, where
      k is the wave number. From very high-resolution numerical simulations, in the
      limit of vanishing viscosity, we find evidence for multiscaling of velocity
      structure functions which cannot be falsified by standard tests. We find a new
      artifact in which logarithmic corrections can appear disguised as anomalous
      scaling and conclude that bifractal scaling is likely.

PMID- 16090176
TI  - Kinematic characterization of valvular opening.
AB  - The evaluation of the valvular opening due to a pulse flow, as is the case of
      cardiac valves, requires the knowledge of the leaflets material properties and
      the coupled solution of the fluid and solid equations. This approach is not
      commonly feasible. A different approach is introduced here to describe the
      opening behavior of valvular leaflets by a functional kinematic relationship. The
      asymptotic analysis, in the limit of leaflet opening without vortex shedding, is
      presented for a two-dimensional rigid leaflet model under the irrotational
      scheme. The approach is then verified by numerical solution of the Navier-Stokes
      equation in asymptotic and nonasymptotic conditions.

PMID- 16090177
TI  - Breakdown of Kolmogorov scaling in models of cluster aggregation.
AB  - We describe a model of cluster aggregation with a source which provides a rare
      example of an analytically tractable turbulent system. The steady state is
      characterized by a constant mass flux from small masses to large. Thus it can be
      studied using a phenomenological theory, inspired by Kolmogorov's 1941 theory,
      which assumes constant flux and self-similarity. We prove that such self
      similarity is violated in dimensions less than or equal to two. We then use
      dynamical renormalization group techniques to show that the scaling of multipoint
      correlation functions implies nontrivial multifractality. The analytical results
      are supported by Monte Carlo simulations.

PMID- 16090161
TI  - Measurements of branching fractions and time-dependent CP-violating asymmetries
      in B --> eta'K decays.
AB  - We present measurements of the B --> eta(')K branching fractions; for B(+) -->
      eta(')K(+) we measure also the time-integrated charge asymmetry Alpha(ch), and
      for B(0) --> eta(')K(0)(S) the time-dependent CP-violation parameters S and C.
      The data sample corresponds to 232 x 10(6) BB pairs produced by e(+)e(-)
      annihilation at the Upsilon (4S). The results are Beta(B --> eta(')K(+)) = (68.9
      +/- 2.0 +/- 3.2) x 10(-6), Beta(B(0) --> eta(')K(0)) = (67.4 +/- 3.2) x 10(-6),
      Alpha(ch) = 0.033 +/- 0.028 +/- 0.005, S = 0.30 +/- 0.140 +/- 0.02, and C = -0.21
      +/- 0.10 +/- 0.02, where the first error quoted is statistical and the second is
      systematic.

PMID- 16090178
TI  - Collective emittance exchange with linear space charge forces and linear
      coupling.
AB  - We show that pronounced collective nonlinear behavior is present in a beam with
      linear coupling and space charge as described by the complete second order moment
      equations. The collective effects result in a shifted and broadened resonance
      condition as well as saturation effects in the emittance transfer. For slow stop
      band crossing either the beam evolves along a skewed matched solution with full
      emittance exchange or the exchange is hindered by collective space charge
      effects, depending on the emittance ratio and direction of crossing.

PMID- 16090179
TI  - Study of electron-beam propagation through preionized dense foam plasmas.
AB  - The transport of an intense electron-beam produced by the Vulcan petawatt laser
      through dense plasmas has been studied by imaging with high resolution the
      optical emission due to electron transit through the rear side of coated foam
      targets. It is observed that the MeV-electron beam undergoes strong filamentation
      and the filaments organize themselves in a ringlike structure. This behavior has
      been modeled using particle-in-cell simulations of the laser-plasma interaction
      as well as of the transport of the electron beam through the preionized plasma.
      In the simulations the filamentary structures are reproduced and attributed to
      the Weibel instability.

PMID- 16090180
TI  - Two-dimensional structure and particle pinch in tokamak H mode.
AB  - Two-dimensional structures of the electrostatic potential, density, and flow
      velocity near the edge of a tokamak plasma are investigated. The model includes
      the nonlinearity in bulk-ion viscosity and turbulence-driven shear viscosity. For
      the case with the strong radial electric field (H mode), a two-dimensional
      structure in a transport barrier is obtained, giving a poloidal shock with a
      solitary radial electric field profile. The inward particle pinch is induced from
      this poloidal asymmetric electric field, and increases as the radial electric
      field becomes stronger. The abrupt increase of this inward ion and electron flux
      at the onset of L- to H-mode transition explains the rapid establishment of the
      density pedestal, which is responsible for the observed spontaneous self
      reorganization into an improved confinement regime.

PMID- 16090181
TI  - Plasma ion evolution in the wake of a high-intensity ultrashort laser pulse.
AB  - Experimental investigations of the late-time ion structures formed in the wake of
      an ultrashort, intense laser pulse propagating in a tenuous plasma have been
      performed using the proton imaging technique. The pattern found in the wake of
      the laser pulse shows unexpectedly regular modulations inside a long, finite
      width channel. On the basis of extensive particle in cell simulations of the
      plasma evolution in the wake of the pulse, we interpret this pattern as due to
      ion modulations developed during a two-stream instability excited by the return
      electric current generated by the wakefield.

PMID- 16090182
TI  - Satellite band in the rovibrational spectrum of CO2 in helium droplets.
AB  - Pulsed infrared (nu approximately 2350 cm(-1)) laser excitation spectra of CO2
      molecules embedded in helium droplets are reported. The spectra exhibit a sharp
      R(0) rovibrational line accompanied by a weak broader (deltanu approximately 10
      cm(-1)) satellite band, which is shifted by 14 cm(-1) towards higher frequencies.
      We assign this satellite band to a simultaneous rovibrational excitation of a
      molecule and its helium solvation shell. The results are rationalized within a
      model, which includes coupling of the rotational states of a molecule and a ring
      of He atoms.

PMID- 16090183
TI  - Multivariate analysis of single-molecule spectra: surpassing spectral diffusion.
AB  - The full exploitation of single-molecule spectroscopy in disordered systems is
      often hampered by spectral diffusion processes of the optical transitions due to
      structural fluctuations in the local environment of the probe molecule which
      leads to temporal averaging of the signal. Multivariate statistical pattern
      recognition techniques, originally developed for single-molecule cryoelectron
      microscopy, allow us to retrieve detailed information from optical single
      molecule spectra. As an example, we present the phonon side band of the B800
      excitations of the light-harvesting 2 (LH2) complex from Rhodospirillum
      molischianum, revealing the electron-phonon coupling strength for these
      transitions. The measured Debye-Waller factors, ranging from 0.4 to 0.9, fall in
      the regime of weak electron-phonon coupling.

PMID- 16090184
TI  - Electron-beam-induced disordering of the Si(001)-c(4 x 2) surface structure.
AB  - An electron beam (EB) irradiation effect on the Si(001)-c(4 x 2) surface was
      investigated by using low-energy electron diffraction. Quarter-order spots become
      dim and streaky by EB irradiation below approximately 40 K, indicating a
      disordering in the c(4 x 2) arrangement of buckled dimers. A quantitative
      analysis of decreasing rates of the spot intensity at various conditions of beam
      current, beam energy, and substrate temperature leads to a proposal for a
      mechanism of the disordering in the buckled-dimer arrangement in terms of
      electronic excitation, electron-phonon coupling, and carrier concentration.

PMID- 16090185
TI  - New helical chain structure for scandium at 240 GPa.
AB  - X-ray diffraction experiments were carried out at 297 K in order to study
      structural-phase transitions of the trivalent rare-earth metal scandium (Sc) at
      pressures of up to 297 GPa. Four stages of structural transition were observed
      around 23, 104, 140, and 240 GPa. The crystal structure of the highest-pressure
      phase, Sc-V, was found to be a hexagonal lattice (S.G.: P6(1)22 or P6(5)22)
      consisting of 6-screw helical chains. The lattice can be derived from modulations
      of the interplane stacking of the (111) planes in an fcc arrangement. The
      occurrence of an anisotropic structure suggests the importance of interactions
      between 3d orbitals with their nearest-neighbor atoms.

PMID- 16090186
TI  - Starlike micelles with starlike interactions: a quantitative evaluation of
      structure factors and phase diagram.
AB  - Starlike PEP-PEO block copolymer micelles offer the possibility to investigate
      the phase behavior and interactions of regular star polymers (ultrasoft
      colloids). Micellar functionality f can be smoothly varied by changing solvent
      composition (interfacial tension). Structure factors obtained by small-angle
      neutron-scattering can be quantitatively described in terms of an effective
      potential for star polymers. The experimental phase diagram reproduces to a high
      level of accuracy the predicted liquid-solid transition. Whereas for intermediate
      f a bcc phase is observed, for high f the formation of a fcc phase is preempted
      by glass formation.

PMID- 16090187
TI  - High-pressure melting of MgSiO3.
AB  - The melting curve of MgSiO(3) perovskite has been determined by means of ab
      initio molecular dynamics complemented by effective pair potentials, and a new
      phenomenological model of melting. Using first principles ground state
      calculations, we find that the MgSiO(3) perovskite phase transforms into post
      perovskite at pressures above 100 GPa, in agreement with recent theoretical and
      experimental studies. We find that the melting curve of MgSiO(3), being very
      steep at pressures below 60 GPa, rapidly flattens on increasing pressure. The
      experimental controversy on the melting of the MgSiO(3) perovskite at high
      pressures is resolved, confirming the data by Zerr and Boehler.

PMID- 16090188
TI  - Localized growth modes, dynamic textures, and upper critical dimension for the
      Kardar-Parisi-Zhang equation in the weak-noise limit.
AB  - A weak-noise scheme is applied to the Kardar-Parisi-Zhang equation for a growing
      interface in all dimensions. It is shown that the solutions can be interpreted in
      terms of a growth morphology of a dynamically evolving texture of localized
      growth modes with superimposed diffusive modes. By applying Derrick's theorem, it
      is conjectured that the upper critical dimension is four.

PMID- 16090189
TI  - Statics and dynamics of single DNA molecules confined in nanochannels.
AB  - The successful design of nanofluidic devices for the manipulation of biopolymers
      requires an understanding of how the predictions of soft condensed matter physics
      scale with device dimensions. Here we present measurements of DNA extended in
      nanochannels and show that below a critical width roughly twice the persistence
      length there is a crossover in the polymer physics.

PMID- 16090190
TI  - Origin and activity of oxidized gold in water-gas-shift catalysis.
AB  - As a promising route for large-scale H2 production, the water-gas-shift reaction
      (WGS, CO + H(2)O-->CO(2) + H(2)) on ceria-supported Au catalysts is of enormous
      potential in efforts to move towards a hydrogen economy. Recent research suggests
      that this reaction is in fact catalyzed by Au cations instead of the
      conventionally regarded metallic Au particles. Here density functional theory
      calculations demonstrate that the presence of empty localized nonbonding f states
      in CeO2 permits the oxidation of Au, enabling subsequent CO adsorption. A
      feasible reaction pathway leading to H2 production is identified, and it is
      concluded that four to six atom Au clusters at the O-vacancy sites of ceria
      catalyze the WGS reaction.

PMID- 16090191
TI  - Atomistic view of the recombinative desorption of H2 from H/Si(100).
AB  - Scanning tunneling microscopy is employed to investigate the recombinative
      desorption of H2 from hydrogenated Si(100) surfaces consisting of dihydride
      (SiH2) and monohydride (SiH) surface species organized in (1 x 1), (3 x 1), and
      (2 x 1) configurations. The results show that desorption from dihydrides involves
      a pair of neighboring dihydrides linked along the tetrahedral bond direction.
      Dihydrides in (3 x 1) domains are separated in the same direction by
      monohydrides, and desorption from a pair is geometrically impossible. The same
      desorption mechanism nevertheless applies via first a position switching of
      dihydrides with neighboring monohydrides.

PMID- 16090192
TI  - Effect of dynamical coulomb correlations on the fermi surface of Na0.3CoO2.
AB  - The t(2g) quasiparticle spectra of Na(0.3)CoO(2) are calculated within the
      dynamical mean field theory. It is shown that as a result of dynamical Coulomb
      correlations charge is transferred from the nearly filled e(g(')) subbands to the
      a(1g) band, thereby reducing orbital polarization among Co t(2g) states.
      Dynamical correlations therefore stabilize the small e(g(')) Fermi surface
      pockets, in contrast to angle-resolved photoemission data, which do not reveal
      these pockets.

PMID- 16090193
TI  - Spin polarized tunneling at finite bias.
AB  - A mesoscopic spin valve is used to determine the dynamic spin polarization of
      electrons tunneling out of and into ferromagnetic (FM) transition metals at
      finite voltages. The dynamic polarization of electrons tunneling out of the FM
      slowly decreases with increasing bias but drops faster and even inverts with
      voltage when electrons tunnel into it. A free-electron model shows that in the
      former case electrons originate near the Fermi level of the FM with large
      polarization whereas in the latter, electrons tunnel into hot electron states for
      which the polarization is significantly reduced. The change in sign is ascribed
      to the matching of the electron wave function inside and outside the tunnel
      barrier.

PMID- 16090194
TI  - Frequency-dependent transport through a quantum dot in the Kondo regime.
AB  - We study the ac conductance and equilibrium current fluctuations of a Coulomb
      blockaded quantum dot in the Kondo regime. To this end we have developed an
      extension of the numerical renormalization group suitable for the nonperturbative
      calculation of finite-frequency transport properties. We demonstrate that ac
      transport gives access to the many-body resonance in the equilibrium spectral
      density. It provides a new route for measuring this key signature of Kondo
      physics, which so far has defied direct experimental observation.

PMID- 16090195
TI  - Steady states of a microwave-irradiated quantum-Hall gas.
AB  - We consider effects of a long-wavelength disorder potential on the zero
      conductance state (ZCS) of the microwave-irradiated 2D electron gas. Assuming a
      uniform Hall conductivity, we construct a Lyapunov functional and derive
      stability conditions on the domain structure of the photogenerated fields. We
      solve the resulting equations for a general one-dimensional and certain two
      dimensional disorder potentials, and find nonzero conductances, photovoltages,
      and circulating dissipative currents. In contrast, weak white-noise disorder does
      not destroy the ZCS, but induces mesoscopic current fluctuations.

PMID- 16090196
TI  - Single-shot readout of electron spin states in a quantum dot using spin-dependent
      tunnel rates.
AB  - We present a method for reading out the spin state of electrons in a quantum dot
      that is robust against charge noise and can be used even when the electron
      temperature exceeds the energy splitting between the states. The spin states are
      first correlated to different charge states using a spin dependence of the tunnel
      rates. A subsequent fast measurement of the charge on the dot then reveals the
      original spin state. We experimentally demonstrate the method by performing
      readout of the two-electron spin states, achieving a single-shot visibility of
      more than 80%. We find very long triplet-to-singlet relaxation times (up to
      several milliseconds), with a strong dependence on the in-plane magnetic field.

PMID- 16090197
TI  - Evidence for skyrmion crystallization from NMR relaxation experiments.
AB  - A resistively detected NMR technique was used to probe the two-dimensional
      electron gas in a GaAs/AlGaAs quantum well. The spin-lattice relaxation rate
      (1/T(1)) was extracted at near complete filling of the first Landau level by
      electrons. The nuclear spin of (75)As is found to relax much more efficiently
      with T --> 0 and when a well developed quantum Hall state with R(xx)
      approximately 0 occurs. The data show a remarkable correlation between the
      nuclear spin relaxation and localization. This suggests that the magnetic ground
      state near complete filling of the first Landau level may contain a lattice of
      topological spin texture, i.e., a Skyrmion crystal.

PMID- 16090198
TI  - Coexistence of superconductivity and antiferromagnetism probed by simultaneous
      nuclear magnetic resonance and electrical transport in (TMTSF)2PF6 system.
AB  - We report simultaneous NMR and electrical transport experiments in the pressure
      range near the boundary of the antiferromagnetic spin density wave (SDW)
      insulator and the metallic/superconducting (SC) phase in (TMTSF)2PF6.
      Measurements indicate a tricritical point separating a line of second-order
      SDW/metal transitions from a line of first-order SDW/metal(SC) transitions with
      coexistence of macroscopic regions of SDW and metal(SC) order, with little mutual
      interaction but strong hysteretic effects. NMR results quantify the fraction of
      each phase.

PMID- 16090199
TI  - Line nodes in the superconducting gap function of noncentrosymmetric CePt3Si.
AB  - The superconducting gap structure of recently discovered heavy fermion CePt(3)Si
      without spatial inversion symmetry was investigated by thermal transport
      measurements down to 40 mK. In zero field a residual T-linear term was clearly
      resolved as T --> 0, with a magnitude in good agreement with the value expected
      for a residual normal fluid with a nodal gap structure, together with a T2
      dependence at high temperatures. With an applied magnetic field, the thermal
      conductivity grows rapidly, in dramatic contrast to fully gapped superconductors,
      and exhibits one-parameter scaling with T/sqrt[H]. These results place an
      important constraint on the order parameter symmetry; that is, CePt(3)Si is most
      likely to have line nodes.

PMID- 16090200
TI  - Ferromagnetic 0-pi junctions as classical spins.
AB  - The ground state of highly damped PdNi based 0-pi ferromagnetic Josephson
      junctions shows a spontaneous half quantum vortex, sustained by a supercurrent of
      undetermined sign. This supercurrent flows in the electrode of a Josephson
      junction used as a detector and produces a phi(0)/4 shift in its magnetic
      diffraction pattern. We have measured the statistics of the positive or the
      negative sign shift occurring at the superconducting transition of such a
      junction. The randomness of the shift sign, the reproducibility of its magnitude,
      and the possibility of achieving exact flux compensation upon field cooling are
      the features which show that 0-pi junctions behave as classical spins, just as
      magnetic nanoparticles with uniaxial anisotropy.

PMID- 16090201
TI  - Electrostatic tuning of the superconductor-insulator transition in two
      dimensions.
AB  - Superconductivity has been induced in insulating ultrathin films of amorphous
      bismuth using the electric field effect. The screening of the electron-electron
      interaction was found to increase with electron concentration in a manner
      correlated with the tendency towards superconductivity. This does not preclude an
      increase in the density of states being important in the development of
      superconductivity. The superconductor-insulator transition appears to belong to
      the universality class of the three dimensional XY model.

PMID- 16090202
TI  - Coincidence of checkerboard charge order and antinodal state decoherence in
      strongly underdoped superconducting Bi2Sr2CaCu2O8 + delta).
AB  - The doping dependence of nanoscale electronic structure in superconducting
      Bi(2)Sr(2)CaCu(2)O(8 + delta) is studied by scanning tunneling microscopy. At all
      dopings, the low energy density-of-states modulations are analyzed according to a
      simple model of quasiparticle interference and found to be consistent with Fermi
      arc superconductivity. The superconducting coherence peaks, ubiquitous in near
      optimal tunneling spectra, are destroyed with strong underdoping and a new
      spectral type appears. Exclusively in regions exhibiting this new spectrum, we
      find local "checkerboard" charge ordering of high energy states, with a wave
      vector of Q = (+/- 2pi/4.5a(0),0); (0, +/- 2pi/4.5a(0)) +/- 15%. Surprisingly,
      this spatial ordering of high energy states coexists harmoniously with the low
      energy Bogoliubov quasiparticle states.

PMID- 16090203
TI  - Observation of modulated quadrupolar structures in PrPb3.
AB  - Neutron diffraction measurements have been performed on the cubic compound
      PrPb(3) in a [001] magnetic field to examine the quadrupolar ordering.
      Antiferromagnetic components with q = (1/2 +/- delta 1/2 0), (1/2 1/2 +/- delta
      0) (delta approximately 1/8) are observed below the transition temperature T(Q)
      (0.4 K at H = 0) whose amplitudes vary linear with H and vanish at zero field,
      providing the first evidence for a modulated quadrupolar phase. For H < 1 T, a
      nonsquare modulated state persists even below 100 mK suggesting quadrupole
      moments associated with a Tau(3) doublet ground state to be partially quenched by
      hybridization with conduction electrons.

PMID- 16090204
TI  - Spin correlations in the paramagnetic phase and ring exchange in La2CuO4.
AB  - Spin correlations in the paramagnetic phase of La(2)CuO(4) have been studied
      using polarized neutron scattering, with two important results. First, the
      temperature dependence of the characteristic energy scale of the fluctuations and
      the amplitude of the neutron structure factor are shown to be in quantitative
      agreement with the predictions of the quantum nonlinear sigma model. Second, a
      comparison of a high-temperature series expansion of the equal-time spin
      correlations with the diffuse neutron intensity provides definitive experimental
      evidence for ring exchange.

PMID- 16090205
TI  - Magnetic-field-induced electric polarization in multiferroic nanostructures.
AB  - Magnetic-field-induced electric polarization in nanostructured multiferroic
      composite films was studied by using the Green's function approach. The
      calculations showed that large magnetic-field-induced polarization could be
      produced in multiferroic nanostructures due to enhanced elastic coupling
      interaction. Especially, the 1-3 type films with ferromagnetic nanopillars
      embedded in a ferroelectric matrix exhibited large magnetic-field-induced
      polarization responses, while the 2-2 type films with ferroelectric and
      ferromagnetic nanolaminates showed much weaker magnetoelectric coupling and lower
      magnetic induced polarization due to large in-plane constraint effect, which was
      in agreement with the recent observations.

PMID- 16090206
TI  - Quantum percolation in two-dimensional antiferromagnets.
AB  - The interplay of geometric randomness and strong quantum fluctuations is an
      exciting topic in quantum many-body physics, leading to the emergence of novel
      quantum phases in strongly correlated electron systems. Recent investigations
      have focused on the case of homogeneous site and bond dilution in the quantum
      antiferromagnet on the square lattice, reporting a classical geometric
      percolation transition between magnetic order and disorder. In this study we show
      how inhomogeneous bond dilution leads to percolative quantum phase transitions,
      which we have studied extensively by quantum Monte Carlo simulations. Quantum
      percolation introduces a new class of two-dimensional spin liquids, characterized
      by an infinite percolating network with vanishing antiferromagnetic order
      parameter.

PMID- 16090207
TI  - Clustering of solutions in the random satisfiability problem.
AB  - Using elementary rigorous methods we prove the existence of a clustered phase in
      the random K-SAT problem, for K > or = 8. In this phase the solutions are grouped
      into clusters which are far away from each other. The results are in agreement
      with previous predictions of the cavity method and give a rigorous confirmation
      to one of its main building blocks. It can be generalized to other systems of
      both physical and computational interest.

PMID- 16090208
TI  - Mechanism for designing metallic metamaterials with a high index of refraction.
AB  - We introduce a mechanism for creating artificial high refractive index
      metamaterials by exploiting the existence of subwavelength propagating modes in
      metallic systems. As an example, we investigate analytically and numerically
      metal films with a periodic arrangement of cut-through slits. Because of the
      presence of TEM modes in the slits, for TM polarization such a system can be
      rigorously mapped into a high refractive index dielectric slab when the features
      are smaller than the wavelength of light. The effective refractive index is
      entirely controlled by the geometry of the metal films, is positive, frequency
      independent, and can be made arbitrarily large.

PMID- 16090209
TI  - Voltage control of the spin dynamics of an exciton in a semiconductor quantum
      dot.
AB  - We report the observation of a spin-flip process in a quantum dot whereby a dark
      exciton with total angular momentum L = 2 becomes a bright exciton with L = 1.
      The spin-flip process is revealed in the decay dynamics following nongeminate
      excitation. We are able to control the spin-flip rate by more than an order of
      magnitude simply with a dc voltage. The spin-flip mechanism involves a spin
      exchange with the Fermi sea in the back contact of our device and corresponds to
      the high temperature Kondo regime. We use the Anderson Hamiltonian to calculate a
      spin-flip rate, and we find excellent agreement with the experimental results.

PMID- 16090210
TI  - Domain wall roughness in epitaxial ferroelectric PbZr0.2Ti0.8O3 thin films.
AB  - The static configuration of ferroelectric domain walls was investigated using
      atomic force microscopy on epitaxial PbZr(0.2)Ti(0.8)O(3) thin films.
      Measurements of domain wall roughness reveal a power-law growth of the
      correlation function of relative displacements B(L) alpha L(2zeta) with zeta
      approximately 0.26 at short length scales L, followed by an apparent saturation
      at large L. In the same films, the dynamic exponent mu was found to be
      approximately 0.6 from independent measurements of domain wall creep. These
      results give an effective domain wall dimensionality of d = 2.5, in good
      agreement with theoretical calculations for a two-dimensional elastic interface
      in the presence of random-bond disorder and long-range dipolar interactions.

PMID- 16090211
TI  - Mobile high resolution xenon nuclear magnetic resonance spectroscopy in the
      earth's magnetic field.
AB  - Conventional high resolution nuclear magnetic resonance (NMR) spectra are usually
      measured in homogeneous, high magnetic fields (>1 T), which are produced by
      expensive and immobile superconducting magnets. We show that chemically resolved
      xenon (Xe) NMR spectroscopy of liquid samples can be measured in the Earth's
      magnetic field (5 x 10(-5) T) with a continuous flow of hyperpolarized Xe gas. It
      was found that the measured normalized Xe frequency shifts are significantly
      modified by the Xe polarization density, which causes different dipolar magnetic
      fields in the liquid and in the gas phases.

PMID- 16090212
TI  - Dissipation of spin angular momentum in magnetic switching.
AB  - Applying one ultrashort magnetic field pulse, we observe up to 10 precessional
      switches of the magnetization direction in single crystalline Fe films of 10 and
      15 atomic layers. We find that the rate at which angular momentum is dissipated
      in uniform large angle spin precession increases with time and film thickness,
      surpassing the intrinsic ferromagnetic resonance spin lattice relaxation of Fe by
      nearly an order of magnitude.

PMID- 16090213
TI  - Evidence of supercritical behavior in liquid single crystal elastomers.
AB  - Temperature profiles of the first and the second moment of the nematic order
      parameter distribution function, as determined from the deuteron nuclear magnetic
      resonance line shapes, as well as heat capacity response, provide support for the
      supercritical scenario of the nematic-paranematic phase transition in liquid
      single crystal elastomers. The relative strength of the locked-in internal
      mechanical field with respect to the critical field can be decreased by swelling
      the elastomer samples with low molecular mass nematogen. By increasing the
      concentration of the dopant, critical and below-critical behavior is promoted.

PMID- 16090214
TI  - Experiments on random packings of ellipsoids.
AB  - Recent simulations indicate that ellipsoids can pack randomly more densely than
      spheres and, remarkably, for axes ratios near 1.25:1:0.8 can approach the densest
      crystal packing (fcc) of spheres, with a packing fraction of 74%. We demonstrate
      that such dense packings are realizable. We introduce a novel way of determining
      packing density for a finite sample that minimizes surface effects. We have
      fabricated ellipsoids and show that, in a sphere, the radial packing fraction
      phi(r) can be obtained from V(h), the volume of added fluid to fill the sphere to
      height h. We also obtain phi(r) from a magnetic resonance imaging scan. The
      measurements of the overall density phi(avr), phi(r) and the core density phi(0)
      = 0.74 +/- 0.005 agree with simulations.

PMID- 16090215
TI  - Optimal search strategies for hidden targets.
AB  - What is the fastest way of finding a randomly hidden target? Experimental
      observations reveal that the search behavior of foraging animals is generally
      intermittent: active search phases randomly alternate with phases of fast
      ballistic motion. Here, we study the efficiency of this two state search strategy
      by calculating analytically the mean first passage time at the target. We model
      the perception mechanism involved in the active search phase by a diffusive
      process. We show that the search strategy is optimal when the average duration of
      "motion phases" varies like the power either 3/5 or 2/3 of the average duration
      of "search phases" depending on the regime. This scaling accounts for
      experimental data over a wide range of species, which suggests that the kinetics
      of search trajectories is a determining factor optimized by foragers and that the
      perception activity is adequately described by a diffusion process.

PMID- 16090217
TI  - Differential growth and instability in elastic shells.
AB  - Differential growth in elastic materials can produce stress either through
      incompatibility of growth or by interaction with the surrounding medium. In many
      situations, this stress can be sufficient to induce shape instability in the
      growing medium. To gain better insight in growth-induced instabilities, the
      growth of an elastic shell loaded with hydrostatic pressure or embedded in an
      elastic medium is studied. The residual stress arising from the incompatibility
      of growth and the contact stress arising from the interaction with the
      surrounding medium are computed with respect to growth and geometric parameters
      and critical values for instability are obtained. Depending on these parameters,
      different modes of instability can be obtained.

PMID- 16090216
TI  - Osmotic force-controlled microrheometry of entangled actin networks.
AB  - In studying a magnetic bead's creep response to force pulses in an entangled
      actin network we have found a novel regime where the bead motion obeys a power
      law x(t) approximately t(1/2) over two decades in time. It is flanked by a short
      time regime with x(t) approximately t(3/4) and a viscous with x(t)approximately
      t. In the intermediate regime the creep compliance depends on the actin
      concentration c as c(-beta) with beta approximately 1.1 +/- 0.3. We explain this
      behavior in terms of osmotic restoring force generated by the piling up of
      filaments in front of the moving bead. A model based on this concept predicts
      intermediate x(t) approximately t(1/2) and long-time regimes x(t) approximately t
      in which the compliance varies as c(-4/3), in agreement with experiment.

PMID- 16090218
TI  - Mechanism and site of attack for direct damage to DNA by low-energy electrons.
AB  - We report results on the desorption of OH- induced by 0-19 eV electrons incident
      on self-assembled monolayer films made of single and double DNA strands of
      different orientations with respect to a gold substrate. Such measurements make
      it possible to deduce the mechanism and site of OH- formation within a
      biomolecule as complex as DNA. This type of damage is attributed to dissociative
      electron attachment to the phosphate group of DNA, when it contains the
      counterion H+.

PMID- 16090219
TI  - Non-markovian transport of DNA in microfluidic post arrays.
AB  - We present an analytically solvable model for the transport of long DNA through
      microfluidic arrays of posts. The motion is a repetitive three-part cycle: (i)
      collision with the post and extension of the arms; (ii) rope-over-pulley post
      disengagement; and (iii) a random period of uniform translation before the next
      collision. This cycle, inspired by geometration, is a nonseparable (Scher-Lax)
      continuous-time random walk on a lattice defined by the posts. Upon adopting a
      simple model for the transition probability density on the lattice, we
      analytically compute the mean DNA velocity and dispersivity in the long-time
      limit without any adjustable parameters. The results compare favorably with the
      limited amount of experimental data on separations in self-assembled arrays of
      magnetic beads. The Scher-Lax formalism provides a template for incorporating
      more sophisticated microscale models.

PMID- 16090220
TI  - Asymmetric target patterns in one-dimensional oscillatory media with genuine
      nonlocal coupling.
AB  - We report the observation of a self-organized asymmetric wave source in a one
      dimensional (1D) electrochemical system, namely, the hydrogen oxidation reaction
      on Pt in the presence of poisons. Numerical simulations reveal that the nonlocal
      migration coupling is crucial for the endogenous persistence of the perturbation
      that causes the asymmetry. Experiments and simulations agree perfectly for the
      regular and irregular variant of these asymmetric waves, manifesting the
      existence of nonlocal coupling induced patterns also in physical systems.

PMID- 16090221
TI  - Observation of a power-law memory kernel for fluctuations within a single protein
      molecule.
AB  - The fluctuation of the distance between a fluorescein-tyrosine pair within a
      single protein complex was directly monitored in real time by photoinduced
      electron transfer and found to be a stationary, time-reversible, and non
      Markovian Gaussian process. Within the generalized Langevin equation formalism,
      we experimentally determine the memory kernel K(t), which is proportional to the
      autocorrelation function of the random fluctuating force. K(t) is a power-law
      decay, t(-0.51 +/- 0.07) in a broad range of time scales (10(-3)-10 s). Such a
      long-time memory effect could have implications for protein functions.

PMID- 16090222
TI  - Apex exponents for polymer-probe interactions.
AB  - We consider self-avoiding polymers attached to the tip of an impenetrable probe.
      The scaling exponents gamma(1) and gamma(2), characterizing the number of
      configurations for the attachment of the polymer by one end, or at its midpoint,
      vary continuously with the tip's angle. These apex exponents are calculated
      analytically by epsilon expansion, and numerically by simulations in three
      dimensions. We find that when the polymer can move through the attachment point,
      it typically slides to one end; the apex exponents quantify the entropic barrier
      to threading the eye of the probe.

PMID- 16090223
TI  - Complete condensation in a zero range process on scale-free networks.
AB  - We study a zero range process on scale-free networks in order to investigate how
      network structure influences particle dynamics. The zero range process is defined
      with the rate p(n) = n(delta) at which particles hop out of nodes with n
      particles. We show analytically that a complete condensation occurs when delta <
      or = delta(c) triple bond 1/(gamma-1) where gamma is the degree distribution
      exponent of the underlying networks. In the complete condensation, those nodes
      whose degree is higher than a threshold are occupied by macroscopic numbers of
      particles, while the other nodes are occupied by negligible numbers of particles.
      We also show numerically that the relaxation time follows a power-law scaling tau
      approximately L(z) with the network size L and a dynamic exponent z in the
      condensed phase.

PMID- 16090224
TI  - Quasiperiodic route to chaotic dynamics of internet transport protocols.
AB  - We show that the dynamics of transmission control protocol (TCP) may often be
      chaotic via a quasiperiodic route consisting of more than two independent
      frequencies, by employing a commonly used ns-2 network simulator. To capture the
      essence of the additive increase and multiplicative decrease mechanism of TCP
      congestion control, and to qualitatively describe why and when chaos may occur in
      TCP dynamics, we develop a 1D discrete map. The relevance of these chaotic
      transport dynamics to real Internet connections is discussed.

PMID- 16090225
TI  - Comment on "anomalously hindered E2 strength B(E2;2+1 --> 0+) in 16C".

PMID- 16090227
TI  - Quantum multimode model of elastic scattering from Bose-Einstein condensates.
AB  - Mean field approximation treats only coherent aspects of the evolution of a Bose
      Einstein condensate. However, in many experiments some atoms scatter out of the
      condensate. We study a semianalytic model of two counterpropagating atomic
      Gaussian wave packets incorporating the dynamics of incoherent scattering
      processes. Within the model we can treat processes of the elastic collision of
      atoms into the initially empty modes, and observe how, with growing occupation,
      the bosonic enhancement is slowly kicking in. A condition for the bosonic
      enhancement effect is found in terms of relevant parameters. Scattered atoms form
      a squeezed state. Not only are we able to calculate the dynamics of mode
      occupation, but also the full statistics of scattered atoms.

PMID- 16090228
TI  - Ultracold collisions involving heteronuclear alkali metal dimers.
AB  - We carry out the first quantum dynamics calculations on ultracold atom-diatom
      collisions in isotopic mixtures. The systems studied are spin-polarized 7Li +
      6Li7Li, 7Li + 6Li2, 6Li + 6Li7Li, and 6Li + 7Li2. Reactive scattering can occur
      for the first two systems even when the molecules are in their ground
      rovibrational states, but is slower than vibrational relaxation in homonuclear
      systems. Implications for sympathetic cooling of heteronuclear molecules are
      discussed.

PMID- 16090229
TI  - Multiple-time correlation functions for non-markovian interaction: beyond the
      quantum regression theorem.
AB  - We derive the dynamical equation of the reduced propagator, an object that
      evolves state vectors of the system conditioned to the dynamics of its
      environment, which is not necessarily in the vacuum state at the initial time.
      Such a reduced propagator is essential to obtain multiple-time correlation
      functions (MTCFs). We also study the evolution of MTCFs within the weak-coupling
      limit and show that the quantum regression theorem is, in general, not satisfied.
      We illustrate the theory in two different cases: first, solving an exact model,
      and, second, presenting the results of the numerical integration for a system
      coupled with a thermal environment through a nondiagonal interaction.

PMID- 16090230
TI  - Locking entanglement with a single qubit.
AB  - We study the loss of entanglement of a bipartite state subjected to discarding or
      measurement of one qubit. Examining behavior of different entanglement measures,
      we find that entanglement of formation, entanglement cost, logarithmic
      negativity, and one-way distillable entanglement are lockable measures in that
      they can decrease arbitrarily after measuring one qubit. We prove that any convex
      and asymptotically noncontinuous measure is lockable. As a consequence, all the
      convex-roof measures can be locked. The relative entropy of entanglement is shown
      to be a nonlockable measure.

PMID- 16090231
TI  - High-temperature expansion for nonequilibrium steady states in driven lattice
      gases.
AB  - We develop a controlled high-temperature expansion for nonequilibrium steady
      states of the driven lattice gas, the "Ising model" for nonequilibrium physics.
      We represent the steady state as P(eta) alpha e(-betaH(eta)-psi(eta)) and
      evaluate the lowest order contribution to the nonequilibrium effective
      interaction psi(eta). We see that, in dimensions d > or = 2, all models with
      nonsingular transition rates yield the same summable psi(eta), suggesting the
      possibility of describing the state as a Gibbs state similar to equilibrium. The
      models with the Metropolis rule show exceptional behavior.

PMID- 16090232
TI  - Phase transition with the Berezinskii-Kosterlitz-Thouless singularity in the
      Ising model on a growing network.
AB  - We consider the ferromagnetic Ising model on a highly inhomogeneous network
      created by a growth process. We find that the phase transition in this system is
      characterized by the Berezinskii-Kosterlitz-Thouless singularity, although
      critical fluctuations are absent and the mean-field description is exact. Below
      this infinite order transition, the magnetization behaves as exp((-const/square
      root of(Tc-T)). We show that the critical point separates the phase with the
      power-law distribution of the linear response to a local field and the phase
      where this distribution rapidly decreases. We suggest that this phase transition
      occurs in a wide range of cooperative models with a strong infinite-range
      inhomogeneity.

PMID- 16090233
TI  - Constraining nuclear equations of state using gravitational waves from
      hypermassive neutron stars.
AB  - Latest general relativistic simulations for the merger of binary neutron stars
      with realistic equations of states (EOSs) show that a hypermassive neutron star
      of an ellipsoidal figure is formed after the merger if the total mass is smaller
      than a threshold value which depends on the EOSs. The effective amplitude of
      quasiperiodic gravitational waves from such hypermassive neutron stars is
      approximately 6-7 x 10(-21) at a distance of 50 Mpc, which may be large enough
      for detection by advanced laser interferometric gravitational wave detectors
      although the frequency is high, approximately 3 kHz. We point out that the
      detection of such signals may lead to constraining the EOSs for neutron stars.

PMID- 16090234
TI  - The flatness problem and Lambda.
AB  - By way of a complete integration of the Friedmann equations, in terms of
      observables, it is shown that for the cosmological constant Lambda > 0 there
      exist nonflat Friedmann-Lemaitre-Robertson-Walker models for which the total
      density parameter omega remains approximately 1 throughout the entire history of
      the Universe. Further, it is shown that in a precise quantitative sense these
      models are not finely tuned. When observations are brought to bear on the theory,
      and, in particular, the Wilkinson microwave anisotropy probe observations, they
      confirm that we live in just such a universe. The conclusion holds when the
      classical notion of Lambda is extended to dark energy.

PMID- 16090235
TI  - Hadronic spectrum of a holographic dual of QCD.
AB  - We compute the spectrum of light hadrons in a holographic dual of QCD defined on
      AdS5 x S5 which has conformal behavior at short distances and confinement at
      large interquark separation. Specific hadrons are identified by the
      correspondence of string modes with the dimension of the interpolating operator
      of the hadron's valence Fock state. Higher orbital excitations are matched quanta
      to quanta with fluctuations about the AdS background. Since only one parameter,
      the QCD scale Lambda(QCD), is used, the agreement with the pattern of physical
      states is remarkable. In particular, the ratio of delta to nucleon trajectories
      is determined by the ratio of zeros of Bessel functions.

PMID- 16090236
TI  - Chiral symmetry breaking and the dirac spectrum at nonzero chemical potential.
AB  - The relation between the spectral density of the QCD Dirac operator at nonzero
      baryon chemical potential and the chiral condensate is investigated. We use the
      analytical result for the eigenvalue density in the microscopic regime which
      shows oscillations with a period that scales as 1/V and an amplitude that
      diverges exponentially with the volume V = L4. We find that the discontinuity of
      the chiral condensate is due to the whole oscillating region rather than to an
      accumulation of eigenvalues at the origin. These results also extend beyond the
      microscopic regime to chemical potentials mu approximately 1/L.

PMID- 16090238
TI  - Interpretation of correlations between nuclear observables in rare-earth nuclei.
AB  - We have recently obtained the optimal core-cluster decompositions for an
      extensive set of heavy even-even nuclei in the rare-earth region. The core
      cluster charge products thus deduced are found to be closely correlated with the
      corresponding B(E2) values. We investigate here the strong resemblance of these
      correlations to the corresponding Casten plots, and find that the cluster model
      also predicts a further correlation between core-cluster charge products and the
      nuclear excitation energies, suggesting a new form of Casten plot for these
      energies.

PMID- 16090239
TI  - Fully coupled channel approach to doubly strange s-shell hypernuclei.
AB  - We describe ab initio calculations of doubly strange, S = -2, s-shell hypernuclei
      (4(LambdaLambda)H, 5LambdaLambda)H, 5(LambdaLambda)He, and 6(LambdaLambda)He) as
      a first attempt to explore the few-body problem of the full-coupled channel
      scheme for these systems. The wave function includes LambdaLambda, LambdaSigma,
      NXi, and SigmaSigma channels. Minnesota NN, D2' YN, and simulated YY potentials
      based on the Nijmegen hard-core model are used. Bound-state solutions of these
      systems are obtained. We find that a set of phenomenological B8B8 interactions
      among the octet baryons in S = 0,-1, and -2 sectors, which is consistent with all
      of the available experimental binding energies of S = 0,-1, and -2 s-shell
      (hyper)nuclei, can predict a particle stable bound state of 4(LambdaLambda)H. For
      5(LambdaLambda)H and 5(LambdaLambda)He, LambdaN-SigmaN and XiN-LambdaSigma
      potentials significantly affect the net LambdaLambda-NXi coupling, and a large Xi
      probability is obtained even for a weaker LambdaLambda-NXi potential.

PMID- 16090237
TI  - First measurement of the transverse spin asymmetries of the deuteron in semi
      inclusive deep inelastic scattering.
AB  - First measurements of the Collins and Sivers asymmetries of charged hadrons
      produced in deep-inelastic scattering of muons on a transversely polarized 6LiD
      target are presented. The data were taken in 2002 with the COMPASS spectrometer
      using the muon beam of the CERN SPS at 160 GeV/c. The Collins asymmetry turns out
      to be compatible with zero, as does the measured Sivers asymmetry within the
      present statistical errors.

PMID- 16090240
TI  - The complement: a solution to liquid drop finite size effects in phase
      transitions.
AB  - The effects of the finite size of a liquid drop undergoing a phase transition are
      described in terms of the complement, the largest (but mesoscopic) drop
      representing the liquid in equilibrium with the vapor. Vapor cluster
      concentrations, pressure, and density from fixed mean density lattice gas (Ising)
      calculations are explained in terms of the complement generalization of Fisher's
      model. Accounting for this finite size effect is important for extracting the
      infinite nuclear matter phase diagram from experimental data.

PMID- 16090241
TI  - Optical production of ultracold polar molecules.
AB  - We demonstrate the production of ultracold polar RbCs molecules in their vibronic
      ground state, via photoassociation of laser-cooled atoms followed by a laser
      stimulated state transfer process. The resulting sample of X1Sigma+ (nu = 0)
      molecules has a translational temperature of approximately 100 microK and a
      narrow distribution of rotational states. With the method described here it
      should be possible to produce samples even colder in all degrees of freedom, as
      well as other bialkali species.

PMID- 16090242
TI  - Suppression of spin projection noise in broadband atomic magnetometry.
AB  - We demonstrate that quantum nondemolition measurement, combined with a suitable
      parameter estimation procedure, can improve the sensitivity of a broadband atomic
      magnetometer by reducing uncertainty due to spin projection noise. Furthermore,
      we provide evidence that real-time quantum feedback control offers robustness to
      classical uncertainties, including shot-to-shot atom number fluctuations, that
      would otherwise prevent quantum-limited performance.

PMID- 16090243
TI  - Phase dependence of enhanced ionization in asymmetric molecules.
AB  - We study enhanced ionization (EI) in asymmetric molecules by solving the 3D time
      dependent Schrodinger equation for HeH2+ driven by a few-cycle laser pulse
      linearly polarized along the molecular axis. We find that EI is much stronger
      when the laser's carrier-envelope phase is such that the electric field at the
      peak of the pulse is antiparallel to the permanent dipole of the molecule (PDM).
      This phase dependence is explained by studying the molecule in the presence of a
      static electric field. When this field is antiparallel to the PDM, the energy of
      the dressed ground state moves up (with increasing internuclear distance R) to
      cross with excited states, leading to a stronger ionization via intermediate
      state resonances and via tunneling. We predict analytically the laser and
      molecular parameters at which these crossings are expected to occur in any
      asymmetric molecule.

PMID- 16090244
TI  - State-selective quantum interference observed in the recombination of highly
      charged Hg 75+...78+ mercury ions in an electron beam ion trap.
AB  - We present experimental data on the state-selective quantum interference between
      different pathways of photorecombination, namely, radiative and dielectronic
      recombination, in the KLL resonances of highly charged mercury ions. The
      interference, observed for well resolved electronic states in the Heidelberg
      electron beam ion trap, manifests itself in the asymmetry of line shapes,
      characterized by "Fano factors," which have been determined with unprecedented
      precision, as well as their excitation energies, for several strong dielectronic
      resonances.

PMID- 16090245
TI  - Application of radiative electron capture for the diagnostics of spin-polarized
      ion beams at storage rings.
AB  - It is proposed to apply the radiative electron capture into high-Z projectiles as
      a probe process for measuring the spin polarization of the hydrogenlike ions at
      storage rings. We argue that such polarization measurements are possible since
      the linear polarization of emitted x-ray photons is greatly sensitive to the spin
      states of incoming ions with nuclear spin I > 1/2. In particular, for K-shell
      electron capture into the hydrogenlike ions, the linear polarization of light as
      measured out of the reaction plane is found to be proportional to the degree of
      ion polarization. Detailed computations for the dependence of the photon
      polarization on the ion spin states and projectile energies are carried out for
      the electron recombination into hydrogenlike Bi 82+ ions.

PMID- 16090246
TI  - Photon number squeezing of ultrabroadband laser pulses generated by
      microstructure fibers.
AB  - To the best of our knowledge, we demonstrate for the first time the generation of
      photon number squeezing by spectral filtering for ultrabroadband light generated
      by microstructure fibers at 800 nm. A maximum squeezing of 4.6 dB is observed,
      corresponding to 10.3 dB after correcting for detection losses. We numerically
      analyzed the quantum dynamics of ultrashort laser pulse propagation through
      optical fibers by solving a nonlinear quantum Schrodinger equation that included
      Raman scattering, especially for the quantum correlation of photon number
      fluctuation among frequency modes in broadband pulses.

PMID- 16090247
TI  - Three-dimensional nonlinear lattices: from oblique vortices and octupoles to
      discrete diamonds and vortex cubes.
AB  - We construct a variety of novel localized topological structures in the 3D
      discrete nonlinear Schrodinger equation. The states can be created in Bose
      Einstein condensates trapped in strong optical lattices and crystals built of
      microresonators. These new structures, most of which have no counterparts in
      lower dimensions, range from multipole patterns and diagonal vortices to vortex
      "cubes" (stack of two quasiplanar vortices) and "diamonds" (formed by two
      orthogonal vortices).

PMID- 16090248
TI  - Explanation of the inverse Doppler effect observed in nonlinear transmission
      lines.
AB  - The theory of the inverse Doppler effect recently observed in magnetic nonlinear
      transmission lines is developed. We explain the crucial role of the backward
      spatial harmonic in the occurrence of an inverse Doppler effect and draw
      analogies of the magnetic nonlinear transmission line to the backward wave
      oscillator.

PMID- 16090249
TI  - Dynamics of periodic pulse collisions in a strongly dissipative-dispersive
      system.
AB  - We report on the dynamics of the periodic collision process occurring between
      different pulse bound states in a stretched-pulse erbium-doped fiber laser. The
      acquisition of a large number of second-order correlation traces allows us to
      reconstruct the dynamics of a single collision event. The measurements clearly
      demonstrate that, unlike true solitons in the case of integrable systems, the
      pulses do not fully overlap in the course of a collision. Instead, the collision
      proceeds through the exchange of bonds between the individual pulses constituting
      the bound states.

PMID- 16090250
TI  - Long-distance frequency dissemination with a resolution of 10(-17).
AB  - We use a new technique to disseminate microwave reference signals along ordinary
      optical fiber. The fractional frequency resolution of a link of 86 km in length
      is 10(-17) for a one day integration time, a resolution higher than the stability
      of the best microwave or optical clocks. We use the link to compare the microwave
      reference and a CO2/OsO4 frequency standard that stabilizes a femtosecond laser
      frequency comb. This demonstrates a resolution of 3 x 10(-14) at 1 s. An upper
      value of the instability introduced by the femtosecond laser-based synthesizer is
      estimated as 1 x 10(-14) at 1 s.

PMID- 16090251
TI  - Heavy photon states in photonic chains of resonantly coupled cavities with
      supermonodispersive microspheres.
AB  - We propose and demonstrate a "bottom-up" approach to constructing photonic
      structures for photon manipulation. Supermonodispersive polymer microspheres are
      used as building blocks and a size uniformity better than 0.05% could be obtained
      by sorting the spheres using spectroscopic methods. The spheres are positioned in
      a V groove on a silicon substrate and form a photonic chain with resonant
      coupling of the optical whispering-gallery modes. Photonic band modes are clearly
      observed in fluorescence and resonant scattering spectra, and an excellent
      agreement with a tight-binding model calculation is found. Heavy photon states
      and a group index as high as 40 are obtained.

PMID- 16090252
TI  - Nonlocality in imaging.
AB  - We show how an effective nonlocality in imaging can lead to the sampling of a
      spatial region which is not significantly illuminated by an imaging probe. The
      nonlocality is embodied in the effective nonlocal potential describing inelastic
      scattering which occurs when coupled channel Schrodinger equations are reduced to
      a single integro-differential equation. The context in which this prediction will
      be illustrated is atomic resolution imaging based on energy-loss spectroscopy in
      scanning transmission electron microscopy.

PMID- 16090253
TI  - Complex oscillations and chaos in electrostatic microelectromechanical systems
      under superharmonic excitations.
AB  - In this Letter, the formation of complex oscillations of the type 2n M
      oscillations per period at the Mth superharmonic excitation is reported for
      electrostatic microelectromechanical systems. A dc bias (beyond "dc symmetry
      breaking") and an ac signal (at the Mth superharmonic frequency) with an
      amplitude around "ac symmetry breaking" gives rise to M oscillations per period
      or period M response. On increasing the ac voltage, a cascade of period doubling
      bifurcations take place giving rise to 2n M oscillations per period. An
      interesting chaotic transition (1-band and 2-band chaos) is observed during the
      first period doubling bifurcation. The nonlinear nature of the electrostatic
      force is shown to be responsible for the reported observations.

PMID- 16090254
TI  - Gravity waves at the interface between miscible fluids and at the top of a
      settling suspension.
AB  - Gravity waves were generated at the interface between miscible fluids, or at the
      top of a settling suspension or a fluidized bed. For these three systems the
      dispersion relation was measured and compared to the theory and calculated
      between two buoyant viscous fluids without surface tension. The experimental
      findings are found to be in good agreement with theory when effective viscosity
      and volume-averaged density values are used.

PMID- 16090255
TI  - Compressibility in solar wind plasma turbulence.
AB  - Incompressible magnetohydrodynamics is often assumed to describe solar wind
      turbulence. We use extended self-similarity to reveal scaling in the structure
      functions of density fluctuations in the solar wind. The obtained scaling is then
      compared with that found in the inertial range of quantities identified as
      passive scalars in other turbulent systems. We find that these are not
      coincident. This implies that either solar wind turbulence is compressible or
      that straightforward comparison of structure functions does not adequately
      capture its inertial range properties.

PMID- 16090256
TI  - Role of kinetic effects on the polarization current around a magnetic island.
AB  - The polarization current due to a magnetic island rotating in a tokamak plasma is
      believed to play a central role in the initial evolution of the neoclassical
      tearing mode. Monte Carlo delta f simulations are performed which also cover a
      parameter range that is not amenable to analytic treatment but is relevant to
      experiments. It is shown that the polarization current can change sign when the
      island rotation frequency is of the order of the ion parallel streaming around
      the island. Moreover, the current is reduced when the island width is of the
      order of the ion banana width. Finally, the transition to the enhanced high
      collisionality regime is shown to occur for collision frequencies higher than
      those typical of today's experiments.

PMID- 16090257
TI  - Ion cyclotron production by a four-wave interaction with a helicon pump.
AB  - Ion cyclotron waves at approximately 0.7 the ion gyrofrequency have been observed
      experimentally in the large volume helicon reactor WOMBAT. These waves are highly
      localized along the axis of the device where a 8 cm diameter, 2 m long. Ar II
      plasma column is produced. Spectral measurements reveal a four-wave interaction
      where energy is down-converted to the ion cyclotron mode from the helicon pump.
      The experimental results are explained in terms of a filamentation type
      instability.

PMID- 16090258
TI  - Relaxation to nonequilibrium in expanding ultracold neutral plasmas.
AB  - We investigate the strongly correlated ion dynamics and the degree of coupling
      achievable in the evolution of freely expanding ultracold neutral plasmas. We
      demonstrate that the ionic Coulomb coupling parameter Gamma(i) increases
      considerably in later stages of the expansion, reaching the strongly coupled
      regime despite the well known initial drop of Gamma(i) to order unity due to
      disorder-induced heating. Furthermore, we formulate a suitable measure of
      correlation and show that Gamma(i) calculated from the ionic temperature and
      density reflects the degree of order in the system if it is sufficiently close to
      a quasisteady state. At later times, however, the expansion of the plasma cloud
      becomes faster than the relaxation of correlations, and the system does not reach
      thermodynamic equilibrium anymore.

PMID- 16090259
TI  - Guiding of intense laser pulses in plasma waveguides produced from efficient,
      femtosecond end-pumped heating of clustered gases.
AB  - We demonstrate intense pulse guiding in efficient femtosecond end-pumped
      waveguides generated in clustered gases. This novel scheme provides a route to
      significantly lower on-axis plasma density (< 10(18) cm(-3)) more than is
      feasible in conventional hydrodynamic plasma waveguides. Self-focused propagation
      and strong absorption of intense femtosecond laser pulses are used to produce
      long centimeter scale channels in an argon cluster jet, and a subsequent pulse is
      guided with 3 x 10(17) W cm(-2) intensity and approximately 50% coupling
      efficiency. Preliminary results with hydrogen clusters also show guiding.

PMID- 16090260
TI  - "Work-Hardenable" ductile bulk metallic glass.
AB  - Usually, monolithic bulk metallic glasses undergo inhomogeneous plastic
      deformation and exhibit poor ductility (< 1%) at room temperature. We present a
      new class of bulk metallic glass, which exhibits high strength of up to 2265 MPa
      together with extensive "work hardening" and large ductility of 18%. Significant
      increase in the flow stress was observed during deformation. The "work-hardening"
      capability and ductility of this class of metallic glass is attributed to a
      unique structure correlated with atomic-scale inhomogeneity, leading to an
      inherent capability of extensive shear band formation, interactions, and
      multiplication of shear bands.

PMID- 16090261
TI  - Amorphous metallic plastic.
AB  - We report cerium-based bulk metallic glasses with an exceptionally low glass
      transition temperature Tg, similar to or lower than that of many polymers. We
      demonstrate that, in near-boiling water, these materials can be repeatedly
      shaped, and can thus be regarded as metallic plastics. Their resistance to
      crystallization permits extended forming times above Tg and ensures an adequate
      lifetime at room temperature. Such materials, combining polymerlike thermoplastic
      behavior with the distinctive properties of metallic glasses, are highly unusual
      for metallic alloys and have great potential in applications and can also
      facilitate studies of the supercooled liquid state.

PMID- 16090262
TI  - Widening of phononic transmission gaps via Anderson localization.
AB  - We demonstrate the existence of strong Anderson localization in certain
      disordered phononic systems. As a result, the transmission coefficient of elastic
      waves through a slab of the material practically vanishes, whatever the angle of
      incidence, over a region of frequency much wider than the absolute frequency gap
      of the corresponding ordered system. The phenomenon can be of use in the design
      of phononic systems with very wide absolute transmission gaps.

PMID- 16090263
TI  - Evidence for a magnetic collapse in the epsilon phase of solid oxygen.
AB  - Solid oxygen is the only elementary molecular magnet. Under the very high
      pressure of 96 GPa oxygen transforms into a metal and a superconductor. Theory
      predicts a nonmagnetic state occurring before the transition into the
      superconducting xi phase. Nevertheless, until now there was no direct evidence of
      a magnetic collapse in high-pressure oxygen. For the first time direct
      information is provided on magnetic properties of the epsilon phase, which is
      sandwiched between the antiferromagnetic delta phase and the superconducting xi
      phase. We used magnetic neutron diffraction. The data show that the long-range
      magnetic order disappears at the delta-epsilon transition. The magnetic collapse
      occurs at P approximately equal to 8 GPa, far below the pressure of the insulator
      metal (superconductor) transition. The collapse is preceded by a decrease in
      temperature of transition towards the long-range magnetically ordered state
      (T(LRO)) in the delta phase, at P = 7.6 GPa.

PMID- 16090264
TI  - Electron correlation and fermi surface topology of NaxCoO2.
AB  - The electronic structure of NaxCoO2 revealed by recent photoemission experiments
      shows important deviations from band theory predictions. The six small Fermi
      surface pockets predicted by local-density approximation calculations have not
      been observed as the associated e'(g) band fails to cross the Fermi level for a
      wide range of sodium doping concentration x. In addition, significant bandwidth
      renormalizations of the t(2g) complex have been observed. We show that these
      discrepancies are due to strong electronic correlations by studying the
      multiorbital Hubbard model in the Hartree-Fock and strong-coupling Gutzwiller
      approximation. The quasiparticle dispersion and the Fermi surface topology
      obtained in the presence of strong local Coulomb repulsion are in good agreement
      with experiments.

PMID- 16090265
TI  - Unified description of charge-carrier mobilities in disordered semiconducting
      polymers.
AB  - From a numerical solution of the master equation for hopping transport in a
      disordered energy landscape with a Gaussian density of states, we determine the
      dependence of the charge-carrier mobility on temperature, carrier density, and
      electric field. Experimental current-voltage characteristics in devices based on
      semiconducting polymers are excellently reproduced with this unified description
      of the mobility. At room temperature it is mainly the dependence on carrier
      density that plays an important role, whereas at low temperatures and high fields
      the electric field dependence becomes important. Omission in the past of the
      carrier-density dependence has led to an underestimation of the hopping distance
      and the width of the density of states in these polymers.

PMID- 16090266
TI  - Zitterbewegung of electronic wave packets in III-V zinc-blende semiconductor
      quantum wells.
AB  - We study the zitterbewegung of electronic wave packets in III-V zinc-blende
      semiconductor quantum wells due to spin-orbit coupling. Our results suggest a
      direct experimental proof of this fundamental effect, confirming a long-standing
      theoretical prediction. For electron motion in a harmonic quantum wire, we
      numerically and analytically find a resonance condition maximizing the
      zitterbewegung.

PMID- 16090267
TI  - Supersymmetric quantum-Hall effect on a fuzzy supersphere.
AB  - Supersymmetric quantum-Hall liquids are constructed on a supersphere in a
      supermonopole background. We derive a supersymmetric generalization of the
      Laughlin wave function, which is a ground state of a hard-core OSp(1/2) invariant
      Hamiltonian. We also present excited topological objects, which are fractionally
      charged deficits made by super Hall currents. Several relations between quantum
      Hall systems and their supersymmetric extensions are discussed.

PMID- 16090268
TI  - Direct measurement of quantum confinement effects at metal to quantum-well
      nanocontacts.
AB  - Model metal-semiconductor nanostructure Schottky nanocontacts were made on
      cleaved heterostructures containing GaAs quantum wells (QWs) of varying width and
      were locally probed by ballistic electron emission microscopy. The local Schottky
      barrier was found to increase by approximately 0.140 eV as the QW width was
      systematically decreased from 15 to 1 nm, due mostly to a large (approximately
      0.200 eV) quantum-confinement increase to the QW conduction band. The measured
      barrier increase over the full 1 to 15 nm QW range was quantitatively explained
      when local "interface pinning" and image force lowering effects are also
      considered.

PMID- 16090269
TI  - Franck-Condon blockade and giant Fano factors in transport through single
      molecules.
AB  - We show that Franck-Condon physics leads to a significant current suppression at
      low bias voltages (termed Franck-Condon blockade) in transport through single
      molecules with strong coupling between electronic and vibrational degrees of
      freedom. Transport in this regime is characterized by remarkably large Fano
      factors (10(2)-10(3) for realistic parameters), which arise due to avalanchelike
      transport of electrons. Avalanches occur in a self-similar manner over a wide
      range of time scales, leading to power-law dependences of the current noise on
      frequency and vibrational relaxation rate.

PMID- 16090270
TI  - Cotunneling-mediated transport through excited states in the Coulomb-blockade
      regime.
AB  - We present finite-bias transport measurements on a few-electron quantum dot. In
      the Coulomb-blockade regime, strong signatures of inelastic cotunneling occur
      which can directly be assigned to excited states observed in the nonblockaded
      regime. In addition, we observe structures related to sequential tunneling
      through the dot, occurring after it has been excited by an inelastic cotunneling
      process. We explain our findings using transport calculations within the real
      time Green's function approach, including diagrams up to fourth order in the
      tunneling matrix elements.

PMID- 16090271
TI  - First-principles study of electron-conduction properties of helical gold
      nanowires.
AB  - Multishell helical gold nanowires (HGNs) suspended between semi-infinite
      electrodes are found to exhibit peculiar electron-conduction properties by first
      principles calculations based on the density functional theory. Our results that
      the numbers of conduction channels in the HGNs and their conductances are smaller
      than those expected from a single-atom row nanowire verify the recent experiment.
      In addition, we obtained a more striking result that, in the cases of thin HGNs,
      distinct magnetic fields are induced by the electronic current helically flowing
      around the shells. This finding indicates that the HGNs can be good candidates
      for nanometer-scale solenoids.

PMID- 16090272
TI  - Scaling and universality of integer quantum Hall plateau-to-plateau transitions.
AB  - We have investigated the integer quantum Hall plateau-to-plateau transition in
      two-dimensional electrons confined to AlxGa(1-x)As-Al0.33Ga0.67As
      heterostructures over a broad range of Al concentration x. For x between 0.65%
      and 1.6%, where the dominant contribution to disorder is from the short-range
      alloy potential fluctuations, we observe a perfect power-law scaling in the
      temperature range from 30 mK to 1 K with a critical exponent kappa = 0.42 +/-
      0.01.

PMID- 16090273
TI  - Optical experimental evidence for a universal length scale for the dynamic charge
      inhomogeneity of cuprate superconductors.
AB  - Time-resolved optical experiments can give unique information on the
      characteristic length scales of dynamic charge inhomogeneity on femtosecond time
      scales. From data on the effective quasiparticle relaxation time tau(r) in La(2
      x)SrxCuO4 and Nd(2-x)Ce(x)CuO4, we derive the temperature and doping dependence
      of the intrinsic phonon escape length l(e), which can be a direct measure of
      charge inhomogeneity. Remarkably, a common feature of both p- and n-type cuprates
      is that, as T --> Tc, l(e) approaches the superconducting coherence length l(e) -
      > xi(s)0. In the normal state l(e) is found to be in excellent agreement with the
      mean free path l(m) obtained from the resistivity data and structural coherence
      lengths l(s) from neutron scattering experiments, implying the existence of
      complex intrinsic textures on different length scales which may have a profound
      effect on the functional properties of these materials.

PMID- 16090274
TI  - Evidence for line nodes in the superconducting energy gap of noncentrosymmetric
      CePt3Si from magnetic penetration depth measurements.
AB  - We report measurements of the magnetic penetration depth lambda(T) in high
      quality CePt3Si samples down to 0.049 K. We observe a linear temperature
      dependence below T approximately equal to 0.16Tc, which is interpreted as
      evidence for line nodes in the energy gap of the low-temperature phase of this
      material. A kink in lambda(T) at about 0.53 K may be associated with the second
      superconducting transition recently reported. The results are discussed in terms
      of the symmetry of the superconducting order parameter.

PMID- 16090276
TI  - Magic doping fractions for high-temperature superconductors.
AB  - We report hole-doping dependence of the in-plane resistivity rho(ab) in a cuprate
      superconductor La(2-x)Sr(x)CuO4, carefully examined using a series of high
      quality single crystals. Our detailed measurements find a tendency towards charge
      ordering at particular rational hole-doping fractions of 1/16, 3/32, 1/8, and
      3/16. This observation appears to suggest a specific form of charge order and is
      most consistent with the recent theoretical prediction of the checkerboard-type
      ordering of the Cooper pairs at rational doping fractions x = (2m+1)/2n, with
      integers m and n.

PMID- 16090275
TI  - Momentum dependence of charge excitations in the electron-doped superconductor
      Nd1.85 Ce0.15 CuO4: a resonant inelastic x-ray scattering study.
AB  - We report a resonant inelastic x-ray scattering (RIXS) study of charge
      excitations in the electron-doped high-T(c) superconductor Nd1.85 Ce0.15 CuO4.
      The intraband and interband excitations across the Fermi energy are separated for
      the first time by tuning the experimental conditions properly to measure charge
      excitations at low energy. A dispersion relation with q-dependent width emerges
      clearly in the intraband excitation, while the intensity of the interband
      excitation is concentrated around 2 eV near the zone center. The experimental
      results are consistent with theoretical calculation of the RIXS spectra based on
      the Hubbard model.

PMID- 16090277
TI  - Mn distribution and spin polarization in Ga(1-x)Mn x As.
AB  - Using the density functional full-potential linearized augmented plane wave
      approach, the x-ray absorption and magnetic circular dichroism (XMCD) spectra of
      Ga(1-x)Mn x As are calculated. Significantly, XMCD of Mn is highly sensitive to
      the change in environment, and thus can be utilized to characterize impurity
      distribution. The nature of Mn-induced spin polarization on Ga and As sites,
      vital for the carrier mediated magnetic ordering, is discussed in light of
      computational and experimental results.

PMID- 16090278
TI  - Supersolids versus phase separation in two-dimensional lattice bosons.
AB  - We study the nature of the ground state of the two-dimensional extended boson
      Hubbard model on a square lattice by quantum Monte Carlo methods. We demonstrate
      that strong but finite on-site interaction U along with a comparable nearest
      neighbor repulsion V result in a thermodynamically stable supersolid ground state
      for densities larger than 1/2, in contrast to fillings less than 1/2 or for very
      large U, where the checkerboard supersolid is unstable towards phase separation.
      We discuss the relevance of our results to realizations of supersolids using cold
      bosonic atoms in optical lattices.

PMID- 16090279
TI  - Metamagnetic phase transition of the antiferromagnetic Heisenberg icosahedron.
AB  - The observation of hysteresis effects in single molecule magnets like Mn12
      acetate has initiated ideas of future applications in storage technology. The
      appearance of a hysteresis loop in such compounds is an outcome of their magnetic
      anisotropy. In this Letter we report that magnetic hysteresis occurs in a spin
      system without any anisotropy, specifically where spins mounted on the vertices
      of an icosahedron are coupled by antiferromagnetic isotropic nearest-neighbor
      Heisenberg interaction giving rise to geometric frustration. At T = 0 this system
      undergoes a first-order metamagnetic phase transition at a critical field Bc
      between two distinct families of ground state configurations. The metastable
      phase of the system is characterized by a temperature and field dependent
      survival probability distribution.

PMID- 16090280
TI  - Zero-temperature criticality in the two-dimensional gauge glass model.
AB  - The zero-temperature critical state of the two-dimensional gauge glass model is
      investigated. It is found that low-energy vortex configurations afford a simple
      description in terms of gapless, weakly interacting vortex-antivortex pair
      excitations. A linear dielectric screening calculation is presented in a
      renormalization group setting that yields a power law decay of spin-wave
      stiffness with distance. These properties are in agreement with low-temperature
      specific heat and spin-glass susceptibility data obtained in large-scale
      multicanonical Monte Carlo simulations.

PMID- 16090281
TI  - Possible quantum critical point in La(2/3)Ca(1/3)Mn(1-x)Ga x O3.
AB  - We study the magnetic ground state in La(2/3)Ca(1/3)Mn(1-x)Ga x O3 manganites,
      where a quantum critical point (QCP) has been theoretically predicted. The
      metallic ferromagnetic ground state for low Ga doping breaks down for x > or =
      0.11, an insulating state being established at low temperatures. Long-range
      ferromagnetism coexists with short-range magnetic correlations in the
      concentration range 0.11 < or = x < or = 0.145 while only the short-range
      correlations survive for x > or = 0.16. We discuss the implications of such a QCP
      to the physics of manganites and compare to other QCP systems.

PMID- 16090282
TI  - Cooperative density wave and giant spin gap in the quarter-filled zigzag electron
      ladder.
AB  - Strong cooperative interactions occur between four different broken symmetries
      involving charge ordering and bond distortions in the quarter-filled correlated
      zigzag electron ladder. The ground state is singlet, with spin gap several times
      larger than in the spin-Peierls state of the one-dimensional quarter-filled chain
      with the same parameters. We propose the quarter-filled zigzag electron ladder
      model for several different organic charge transfer solids with coupled pairs of
      quasi-one-dimensional stacks, in which the spin-gap transition temperatures are
      unusually high.

PMID- 16090283
TI  - Analytic relations between localizable entanglement and string correlations in
      spin systems.
AB  - We study the relation between the recently defined localizable entanglement and
      generalized correlations in quantum spin systems. Differently from the current
      belief, the localizable entanglement is always given by the average of a
      generalized string. Using symmetry arguments we show that in most spin-1/2 and
      spin-1 systems the localizable entanglement reduces to the spin-spin or string
      correlations, respectively. We prove that a general class of spin-1 systems,
      which includes the Heisenberg model, can be used as a perfect quantum channel.
      These conclusions are obtained in analytic form and confirm some results found
      previously on numerical grounds.

PMID- 16090284
TI  - Molecular engineering of antiferromagnetic rings for quantum computation.
AB  - The substitution of one metal ion in a Cr-based molecular ring with dominant
      antiferromagnetic couplings allows the engineering of its level structure and
      ground-state degeneracy. Here we characterize a Cr7Ni molecular ring by means of
      low-temperature specific-heat and torque-magnetometry measurements, thus
      determining the microscopic parameters of the corresponding spin Hamiltonian. The
      energy spectrum and the suppression of the leakage-inducing S mixing render the
      Cr7Ni molecule a suitable candidate for the qubit implementation, as further
      substantiated by our quantum-gate simulations.

PMID- 16090285
TI  - Method for analyzing second-order phase transitions: application to the
      ferromagnetic transition of a polaronic system.
AB  - A new method for analyzing second-order phase transitions is presented and
      applied to the polaronic system La(0.7)Ca(0.3)MnO3. It utilizes heat capacity and
      thermal expansion data simultaneously to correctly predict the critical
      temperature's pressure dependence. Analysis of the critical phenomena reveals
      second-order behavior and an unusually large heat capacity exponent.

PMID- 16090286
TI  - Spin-dependent resonant tunneling through quantum-well states in magnetic
      metallic thin films.
AB  - Quantum-well (QW) states in nonmagnetic metal films between magnetic layers are
      known to be important in spin-dependent transport, but QW states in magnetic
      films remains elusive. Here we identify the conditions for resonant tunneling
      through QW states in magnetic films and report first principles calculations of
      Fe/MgO/FeO/Fe/Cr and Co/MgO/Fe/Cr. We show that, at resonance, the current
      increases by 1 to 2 orders of magnitude. The tunneling magnetoresistance ratio is
      much larger than in simple spin tunnel junctions and is positive (negative) for
      majority- (minority-) spin resonances, with a large asymmetry between positive
      and negative biases. The results can serve as a basis for novel spintronic
      devices.

PMID- 16090287
TI  - Deroughening of domain wall pairs by dipolar repulsion.
AB  - As a magnetic domain wall propagates under small fields through a random
      potential, it roughens as a result of weak collective pinning, known as creep.
      Using Kerr microscopy, we report experimental evidence of a surprising
      deroughening of wall pairs in the creep regime, in a 0.5 nm thick Co layer with
      perpendicular anisotropy. A bound state is found in cases where two rough domains
      nucleated far away from one another and first growing under the action of a
      magnetic field eventually do not merge. The two domains remain separated by a
      strip of unreversed magnetization, characterized by flat edges and stabilized by
      dipolar fields. A creep theory that includes dipolar interactions between domains
      successfully accounts for (i) the domain wall deroughening as the width of the
      strip decreases and (ii) the quasistatic and dynamic field dependence of the
      strip width s.

PMID- 16090288
TI  - Intersubband exciton relaxation dynamics in single-walled carbon nanotubes.
AB  - We study exciton (EX) dynamics in single-walled carbon nanotubes (SWNTs) included
      in polymethylmethacrylate by two-color pump-probe experiments with unprecedented
      temporal resolution. In the semiconducting SWNTs, we resolve the intersubband
      energy relaxation from the EX2 to the EX1 transition and find time constants of
      about 40 fs. The observation of a photoinduced absorption band strictly
      correlated to the photobleaching of the EX1 transition supports the excitonic
      model for primary excitations in SWNTs. We also detect in the time domain
      coherent oscillations due to the radial breathing modes at approximately 250 cm(
      1).

PMID- 16090289
TI  - Microscale localized spectroscopy with a magnetic resonance force microscope.
AB  - Magnetic resonance force microscopy is combined with spin-echo spectroscopy to
      obtain spatially and spectrally resolved NMR signals of micrometer-scale objects.
      The experimental spatial resolution for the demonstration experiment on a sample
      consisting of Ba(ClO3)2.H2O and (NH4)2SO4 single crystals is 3.4 microm. The
      spectral resolution of 3.4 kHz is sample limited. Improvements in resolution and
      extensions of the method to more than one spatial dimension and to
      multidimensional spectroscopy are possible.

PMID- 16090290
TI  - Two scenarios for avalanche dynamics in inclined granular layers.
AB  - We report experimental measurements of avalanche behavior of thin granular layers
      on an inclined plane for low volume flow rate. The dynamical properties of
      avalanches were quantitatively and qualitatively different for smooth glass beads
      compared to irregular granular materials such as sand. Two scenarios for granular
      avalanches on an incline are identified, and a theoretical explanation for these
      different scenarios is developed based on a depth-averaged approach that takes
      into account the differing rheologies of the granular materials.

PMID- 16090291
TI  - How white noise generates power-law switching in bacterial flagellar motors.
AB  - The clockwise (CW) or counterclockwise (CCW) spinning of a bacterial flagellar
      motor is controlled by the concentration [Y] of a phosphorylated protein, CheY-P.
      Representing the stochastic switching behavior of the motor by a dynamical two
      state (CW and CCW) model, whose energy levels fluctuate in time (t) as [Y](t)
      fluctuates, we show that temporal fluctuations in [Y](t) can generate a power-law
      distribution for the durations of the CCW states, in agreement with recent
      experiments. Correlations between the duration times of nearby CCW (CW) intervals
      are predicted by our model, and shown to exist in the experimental data and to
      affect the power spectrum for motor switching.

PMID- 16090292
TI  - Dynamical arrest in attractive colloids: the effect of long-range repulsion.
AB  - We study gelation in suspensions of model colloidal particles with short-ranged
      attractive and long-ranged repulsive interactions by means of three-dimensional
      fluorescence confocal microscopy. At low packing fractions, particles form stable
      equilibrium clusters. Upon increasing the packing fraction the clusters grow in
      size and become increasingly anisotropic until finally associating into a fully
      connected network at gelation. We find a surprising order in the gel structure.
      Analysis of spatial and orientational correlations reveals that the gel is
      composed of dense chains of particles constructed from face-sharing tetrahedral
      clusters. Our findings imply that dynamical arrest occurs via cluster growth and
      association.

PMID- 16090293
TI  - Orthorhombic Fddd network in triblock and diblock copolymer melts.
AB  - The phase behavior of ABC triblock and AB diblock copolymer melts is investigated
      by self-consistent field theory, while allowing for (among other candidates) the
      orthorhombic Fddd (O70) network phase identified in recent experiments with
      poly(isoprene-b-styrene-b-ethylene oxide) (ISO) triblocks. Predicted phase
      diagrams for triblocks similar to ISO contain an O70 phase bordered by gyroid,
      lamellar, and alternating gyroid phases, in agreement with experiment. The O70
      network is also found to be stable in diblock melts within a narrow region that
      overlaps the weak segregation end of the gyroid region found in previous
      calculations.

PMID- 16090294
TI  - Comparative study of C-H stretch and bend vibrations in methane activation on
      Ni(100) and Ni(111).
AB  - State-resolved measurements on clean Ni(100) and Ni(111) surfaces quantify the
      reactivity of CH4 excited to v = 3 of the nu4 bend vibration. A comparison with
      prior data reveals that 3nu4 is significantly less effective than the nu3 C-H
      stretch at promoting dissociative chemisorption, even though 3nu4 contains 30%
      more energy. These results contradict statistical theories of gas-surface
      reactivity, provide clear evidence for vibrational mode specificity in a gas
      surface reaction, and point to a central role for C-H stretching motion along the
      reaction path to dissociative chemisorption.

PMID- 16090295
TI  - Adaptability and "intermediate phase" in randomly connected networks.
AB  - We present a simple model that enables us to analytically characterize a floppy
      to rigid transition and an associated self-adaptive intermediate phase in a
      random bond network. In this intermediate phase, the network adapts itself to
      lower the stress due to constraints. Our simulations verify this picture. We use
      these insights to identify applications of these ideas in computational problems
      such as vertex cover and K-satisfiability.

PMID- 16090296
TI  - Comment on "Temperature in nonequilibrium systems with conserved energy".

PMID- 16090298
TI  - Comment on "Dynamical role of anyonic excitation statistics in rapidly rotating
      bose gases".

PMID- 16090300
TI  - Comment on "Thermal contraction of carbon fullerenes and nanotubes".

PMID- 16090302
TI  - Comment on "Momentum-dependent energy losses in core level photoemission spectra
      of poorly conducting metals".

PMID- 16090304
TI  - Confinement induced molecules in a 1D Fermi gas.
AB  - We have observed two-particle bound states of atoms confined in a one-dimensional
      matter waveguide. These bound states exist irrespective of the sign of the
      scattering length, contrary to the situation in free space. Using radio-frequency
      spectroscopy we have measured the binding energy of these dimers as a function of
      the scattering length and confinement and find good agreement with theory. The
      strongly interacting one-dimensional Fermi gas which we create in an optical
      lattice represents a realization of a tunable Luttinger liquid.

PMID- 16090305
TI  - Full counting statistics with spin-sensitive detectors reveals spin singlets.
AB  - We study the full counting statistics of electric current to several drain
      terminals with spin-dependent entrance conductances. We show that the statistics
      of charge transfers can be interpreted in terms of single electrons and spin
      singlet pairs coming from the source. If the source contains transport channels
      of high transparency, a significant fraction of electrons comes in spin-singlet
      pairs.

PMID- 16090306
TI  - Pulsar kicks via spin-1 color superconductivity.
AB  - We propose a new neutrino propulsion mechanism for neutron stars which can lead
      to strong velocity kicks, needed to explain the observed bimodal velocity
      distribution of pulsars. The spatial asymmetry in the neutrino emission is
      naturally provided by a stellar core containing spin-1 color-superconducting
      quark matter in the A phase. The neutrino propulsion mechanism switches on when
      the stellar core temperature drops below the transition temperature of this
      phase.

PMID- 16090307
TI  - Measuring the 13 neutrino mixing angle and the CP phase with neutrino telescopes.
AB  - The observed excess of high-energy cosmic rays from the Galactic plane in the
      energy range around 10(18) eV may be explained by neutron primaries generated in
      the photodissociation of heavy nuclei. In this scenario, lower-energy neutrons
      decay before reaching the Earth and produce a detectable flux in a 1 km(3)
      neutrino telescope. The initial flavor composition of the neutrino flux,
      phi(nu(e)):phi(nu(mu)):phi(nu(tau))=1:0:0, permits a combined nu(mu)/nu(tau)
      appearance and nu(e) disappearance experiment. The observable flux ratio
      phi(nu(mu))/phi(nu(e)+nu(tau) at Earth depends on the 13 mixing angle theta(13)
      and the leptonic CP phase delta(CP), thus opening a new way to measure these two
      quantities.

PMID- 16090308
TI  - Deconfinement phase transition in a 3D nonlocal U(1) lattice gauge theory.
AB  - We introduce a 3D compact U(1) lattice gauge theory having nonlocal interactions
      in the temporal direction, and study its phase structure. The model is relevant
      for the compact QED3 and strongly correlated electron systems like the t-J model
      of cuprates. For a power-law decaying long-range interaction, which simulates the
      effect of gapless matter fields, a second-order phase transition takes place
      separating the confinement and deconfinement phases. For an exponentially
      decaying interaction simulating matter fields with gaps, the system exhibits no
      signals of a second-order transition.

PMID- 16090310
TI  - Precise determination of the strangeness magnetic moment of the nucleon.
AB  - By combining the constraints of charge symmetry with new chiral extrapolation
      techniques and recent low mass quenched lattice-QCD simulations of the individual
      quark contributions to the magnetic moments of the nucleon octet, we obtain a
      precise determination of the strange magnetic moment of the proton. The result,
      namely, G(s)(M)=(-0.046 +/- 0.019)mu(N) is consistent with the latest
      experimental measurements but an order of magnitude more precise. This poses a
      tremendous challenge for future experiments.

PMID- 16090311
TI  - Two-photon-exchange correction to parity-violating elastic electron-proton
      scattering.
AB  - Higher-order QED effects play an important role in precision measurements of
      nucleon elastic form factors in electron scattering. Here we introduce a two
      photon-exchange QED correction to the parity-violating polarization asymmetry of
      elastic electron-proton scattering. We calculate this correction in the parton
      model using the formalism of generalized parton distributions, and demonstrate
      that it can reach several percent in certain kinematics, becoming comparable in
      size with existing experimental measurements of strange-quark effects in the
      proton neutral weak current.

PMID- 16090312
TI  - Measurement of the kaonic hydrogen x-ray spectrum.
AB  - The DEAR (DAPhiNE exotic atom research) experiment measured the energy of x rays
      emitted in the transitions to the ground state of kaonic hydrogen. The measured
      values for the shift epsilon and the width Gamma of the 1s state due to the K(-)p
      strong interaction are epsilon(1s)=-193 +/- 37 (stat) +/- 6 (syst) eV and
      Gamma(1s)=249 +/- 111 (stat) +/- 30 (syst) eV, the most precise values yet
      obtained. The pattern of the kaonic hydrogen K-series lines, K(alpha), K(beta),
      and K(gamma), was disentangled for the first time.

PMID- 16090313
TI  - Evidence for a kaon-bound state K(-)pp produced in K(-) absorption reactions at
      rest.
AB  - We have searched for a deeply bound kaonic state by using the FINUDA spectrometer
      installed at the e(+)e(-) collider DAPhiNE. Almost monochromatic K(-)'s produced
      through the decay of phi(1020) mesons are used to observe K(-) absorption
      reactions stopped on very thin nuclear targets. Taking this unique advantage, we
      have succeeded to detect a kaon-bound state K(-)pp through its two-body decay
      into a Lambda hyperon and a proton. The binding energy and the decay width are
      determined from the invariant-mass distribution as 115(+6)(-5)(stat)(+3)(
      4)(syst) MeV and 67(+14)(-11)(stat)(+2)(-3)(syst) MeV, respectively.

PMID- 16090314
TI  - Ab-initio coupled-cluster study of 16O.
AB  - We report converged results for the ground and excited states and matter density
      of 16O using realistic two-body nucleon-nucleon interactions and coupled-cluster
      methods and algorithms developed in quantum chemistry. Most of the binding is
      obtained with the coupled-cluster singles and doubles approach. Additional
      binding due to three-body clusters (triples) is minimal. The coupled-cluster
      method with singles and doubles provides a good description of the matter
      density, charge radius, charge form factor, and excited states of a one-particle,
      one-hole nature, but it cannot describe the first-excited 0(+) state.
      Incorporation of triples has no effect on the latter finding.

PMID- 16090315
TI  - Measured total cross sections of slow neutrons scattered by gaseous and liquid
      2H(2).
AB  - The total scattering cross sections for slow neutrons with energies E in the
      range 300 neV to 3 meV for gaseous and liquid ortho-2H2 have been measured. The
      cross sections for 2H2 gas are found to be in excellent agreement with both the
      Hamermesh and Schwinger and the Young and Koppel models. For liquid 2H(2), we
      confirm the existing experimental data in the cold neutron range and the
      discrepancy with the gas models. We find a clear 1 / square root[E'] dependence
      at low energies for both states. A simple explanation for the liquid 2H2 cross
      section is offered.

PMID- 16090316
TI  - Use of electron correlation to make attosecond measurements without attosecond
      pulses.
AB  - We describe how correlations between electrons can be used to trace the dynamics
      of correlated two-electron ionization with attosecond precision, without using
      attosecond pulses. The approach is illustrated using the example of Auger or
      Coster-Kronig decay triggered by photoionization with an extreme ultraviolet
      pulse. It requires correlated measurements of angle-resolved energy spectra of
      both the photo- and Auger electrons in the presence of a laser pulse. To
      reconstruct the dynamics, we use not only classical time and energy correlation,
      but also entanglement between the two electrons.

PMID- 16090317
TI  - QED corrections to the parity-nonconserving 6s-7s amplitude in 133Cs.
AB  - The complete gauge-invariant set of the one-loop QED corrections to the parity
      nonconserving 6s-7s amplitude in 133Cs is evaluated to all orders in alphaZ using
      a local version of the Dirac-Hartree-Fock potential. The calculations are
      performed in both length and velocity gauges for the absorbed photon. The total
      binding QED correction is found to be -0.27(3)%. The weak charge of 133Cs,
      derived using two most accurate values of the vector transition polarizability
      beta, is Q(W)=-72.57(46) for beta=26.957(51)a(3)(B) and Q(W)=-73.09(54) for
      beta=27.15(11)a(3)(B). The first value deviates by 1.1sigma from the prediction
      of the standard model, while the second one is in perfect agreement with it.

PMID- 16090318
TI  - Scattering length scaling laws for ultracold three-body collisions.
AB  - We present a simple and unifying picture that provides the energy and scattering
      length dependence for all inelastic three-body collision rates in the ultracold
      regime for three-body systems with short-range two-body interactions. Here, we
      present the scaling laws for vibrational relaxation, three-body recombination,
      and collision-induced dissociation for systems that support s-wave two-body
      collisions. These systems include three identical bosons, two identical bosons,
      and two identical fermions. Our approach reproduces all previous results,
      predicts several others, and gives the general form of the scaling laws in all
      cases.

PMID- 16090319
TI  - Observation of a molecular frame (e, 2e) cross section: an (e, 2e + M) triple
      coincidence study on H(2).
AB  - We report the first experimental results showing transition-specific anisotropy
      of molecular frame (e, 2e) cross sections. Vector correlations between the two
      outgoing electrons and the fragment ion have been measured for specific
      ionization-excitation processes of H2. The results enable us to obtain molecular
      frame (e, 2e) cross sections for transitions to the 2ssigma(g) and 2psigma(u)
      excited states of H(2)(+), thereby making stereodynamics of the electron-molecule
      collisions directly visible.

PMID- 16090320
TI  - Kaonic hydrogen and K(-)p scattering.
AB  - Chiral SU(3) effective field theory in combination with a relativistic coupled
      channels approach is used to perform a novel analysis of the strong-interaction
      shift and width in kaonic hydrogen in view of the new accurate DEAR measurements.
      Questions of consistency with previous K(-)p data are examined. Coulomb and
      isospin breaking effects turn out to be important and are both taken into account
      in this work.

PMID- 16090321
TI  - Optical absorption spectrum of gold atoms deposited on SiO(2) from cavity
      ringdown spectroscopy.
AB  - The optical properties of gold atoms supported on amorphous silica (alpha-SiO2)
      were studied experimentally and theoretically in the visible range. Samples were
      prepared in situ by depositing Au atoms at low coverages (5 x 10(12) cm(-2)) in
      UHV, and the optical absorption spectra were recorded by cavity ringdown
      spectroscopy. The atomic absorption bands can be attributed to gold atoms trapped
      at [triple bond] Si-O(.-) and [triple bond]Si-O(-) defect sites. The absence of
      optical transitions typical for Au(2) shows that the atoms are efficiently
      anchored at these defect sites, preventing diffusion and aggregation.
      Furthermore, these experimental results reveal that it is now possible to study
      optical properties of well-defined nanostructures at surface coverages as low as
      5 x 10(11) cm(-2).

PMID- 16090322
TI  - Inducing chaos by resonant perturbations: theory and experiment.
AB  - We propose a scheme to induce chaos in nonlinear oscillators that either are by
      themselves incapable of exhibiting chaos or are far away from parameter regions
      of chaotic behaviors. Our idea is to make use of small, judiciously chosen
      perturbations in the form of weak periodic signals with time-varying frequency
      and phase, and to drive the system into a hierarchy of nonlinear resonant states
      and eventually into chaos. We demonstrate this method by using numerical examples
      and a laboratory experiment with a Duffing type of electronic circuit driven by a
      phase-locked loop. The phase-locked loop can track the instantaneous frequency
      and phase of the Duffing circuit and deliver resonant perturbations to generate
      robust chaos.

PMID- 16090323
TI  - A chiral granular gas.
AB  - Inspired by rattleback toys, we created small chiral wires that rotate in a
      preferred direction on a vertically oscillating platform and quantified their
      motion with experiment and simulation. We demonstrate experimentally that angular
      momentum of rotation about particle centers of mass is converted to collective
      angular momentum of center-of-mass motion in a granular gas of these wires, and
      we introduce a continuum model that explains our observations.

PMID- 16090324
TI  - Thermal patterning of a critical polymer blend.
AB  - Utilizing the Soret effect, we have employed a moderately focused laser beam (30
      microm, 20 mW) to write spatial composition patterns into layers of the critical
      polymer blend poly(dimethyl siloxane)/poly(ethyl-methyl siloxane) (PDMS/PEMS,
      M(w)=16.4/22.8 kg/mol) both in the one- and in the two-phase region a few degrees
      above and below the critical temperature T(c)=37.7 degrees C. Because of the
      critical divergence of the Soret coefficient, moderate temperature gradients are
      sufficient to induce composition modulations of large amplitude. In the two-phase
      regime the spinodal demixing pattern can be locally manipulated in a controlled
      way. 2D simulations based on a modified Cahn-Hilliard equation are able to
      reproduce the essential spatial and temporal features observed in the
      experiments.

PMID- 16090325
TI  - Anomalous scaling of a passive scalar in turbulence and in equilibrium.
AB  - We analyze the multipoint correlation functions of a tracer in an incompressible
      flow at scales far exceeding the scale L at which fluctuations are generated
      (quasiequilibrium domain) and compare them with the correlation functions at
      scales smaller than L (turbulence domain). We demonstrate that scale invariance
      can be broken in the equilibrium domain and trace this breakdown to the
      statistical integrals of motion (zero modes) as has been done before for
      turbulence. Employing the Kraichnan model of short-correlated velocity we
      identify the new type of zero modes, which break scale invariance and determine
      an anomalously slow decay of correlations at large scales.

PMID- 16090326
TI  - Large-scale structure of passive scalar turbulence.
AB  - We investigate the large-scale statistics of a passive scalar transported by a
      turbulent velocity field by means of direct numerical simulations. We focus on
      scales larger than the characteristic length scale of scalar injection, yet
      smaller than the correlation length of the velocity. We show the existence of
      nontrivial long-range correlations in the form of new power laws for the decay of
      high-order coarse-grained scalar cumulants. This result contradicts the classical
      scenario of Gibbs equilibrium statistics that should hold in the absence of
      scalar flux. The breakdown of "thermal equilibrium" at large scales is traced
      back to the statistical geometry of turbulent dispersion of two scalar blobs. The
      numerical values obtained for the scaling exponents of the coarse-grained scalar
      cumulants are in agreement with recent theoretical results.

PMID- 16090327
TI  - Polarization-reversal-induced damping of left-hand polarized wave on electron
      cyclotron resonance.
AB  - The left-hand polarized wave, which has been believed not to be related to
      electron cyclotron resonance (ECR), is for the first time demonstrated to be
      damped near the ECR point in an inhomogeneously magnetized plasma as a result of
      the polarization reversal to the right-hand polarized wave. The polarization
      reversal is found to be caused by the existence of the boundary between a plasma
      and a vacuum region, the local point of which shifts depending on the plasma
      column radius. This phenomenon is quantitatively explained in terms of the
      dispersion relation including the effect of the radial boundary condition.

PMID- 16090309
TI  - Measurement of the W(+)W(-) production cross section in pp collisions at square
      root[s]=1.96 TeV using dilepton events.
AB  - We present a measurement of the W(+)W(-) production cross section using 184 pb(
      1) of p(p) collisions at a center-of-mass energy of 1.96 TeV collected with the
      Collider Detector at Fermilab. Using the dilepton decay channel W(+)W(-)-
      >l(+)nul(-), where the charged leptons can be either electrons or muons, we find
      17 candidate events compared to an expected background of 5.0(+2.2)(-0.8) events.
      The resulting W(+)W(-) production cross-section measurement of sigma(pp-->W(+)W(
      ))=14.6(+5.8)(-5.1)(stat)(+1.8)(-3.0)(syst) +/- 0.9(lum) pb agrees well with the
      standard model expectation.

PMID- 16090328
TI  - Measurement of the electric fluctuation spectrum of magnetohydrodynamic
      turbulence.
AB  - Magnetohydrodynamic (MHD) turbulence in the solar wind is observed to show the
      spectral behavior of classical Kolmogorov fluid turbulence over an inertial
      subrange and departures from this at short wavelengths, where energy should be
      dissipated. Here we present the first measurements of the electric field
      fluctuation spectrum over the inertial and dissipative wave number ranges in a
      Beta > or approximately = 1 plasma. The k(-5/3) inertial subrange is observed and
      agrees strikingly with the magnetic fluctuation spectrum; the wave phase speed in
      this regime is shown to be consistent with the Alfven speed. At smaller
      wavelengths krho(i) > or = 1 the electric spectrum is enhanced and is consistent
      with the expected dispersion relation of short-wavelength kinetic Alfven waves.
      Kinetic Alfven waves damp on the solar wind ions and electrons and may act to
      isotropize them. This effect may explain the fluidlike nature of the solar wind.

PMID- 16090329
TI  - Role of bremsstrahlung radiation in limiting the energy of runaway electrons in
      tokamaks.
AB  - Bremsstrahlung radiation of runaway electrons is found to be an energy limit for
      runaway electrons in tokamaks. The minimum and maximum energy of runaway electron
      beams is shown to be limited by collisions and bremsstrahlung radiation,
      respectively. It is also found that a massive injection of a high-Z gas such as
      xenon can terminate a disruption-generated runaway current before the runaway
      electrons hit the walls.

PMID- 16090330
TI  - Evidence for the weak steric hindrance scenario in the supercooled-state
      reorientational dynamics.
AB  - We use molecular-dynamics computer simulations to study the translational and
      reorientational dynamics of a glass-forming liquid of dumbbells. For sufficiently
      elongated molecules the standard strong steric hindrance scenario for the
      rotational dynamics is found. However, for small elongations we find a different
      scenario--the weak steric hindrance scenario--caused by a new type of glass
      transition in which the orientational dynamics of the molecule's axis undergoes a
      dynamical transition with a continuous increase of the nonergodicity parameter.
      These results are in agreement with the theoretical predictions by the mode
      coupling theory for the glass transition.

PMID- 16090331
TI  - From random walk to single-file diffusion.
AB  - We report an experimental study of diffusion in a quasi-one-dimensional (q1D)
      colloid suspension which behaves like a Tonks gas. The mean squared displacement
      as a function of time is described well with an ansatz encompassing a time regime
      that is both shorter and longer than the mean time between collisions. The ansatz
      asserts that the inverse mean squared displacement is the sum of the inverse mean
      squared displacement for short time normal diffusion (random walk) and the
      inverse mean squared displacement for asymptotic single-file diffusion (SFD). The
      dependence of the 1D mobility in the SFD on the concentration of the colloids
      agrees quantitatively with that derived for a hard rod model, which confirms for
      the first time the validity of the hard rod SFD theory. We also show that a
      recent SFD theory by Kollmann leads to the hard rod SFD theory for a Tonks gas.

PMID- 16090332
TI  - Selected growth of cubic and hexagonal GaN epitaxial films on polar MgO(111).
AB  - Selected molecular beam epitaxy of zinc blende (111) or wurtzite (0001) GaN films
      on polar MgO(111) is achieved depending on whether N or Ga is deposited first.
      The cubic stacking is enabled by nitrogen-induced polar surface stabilization,
      which yields a metallic MgO(111)-(1 x 1)-ON surface. High-resolution transmission
      electron microscopy and density functional theory studies indicate that the
      atomically abrupt semiconducting GaN(111)/MgO(111) interface has a Mg-O-N-Ga
      stacking, where the N atom is bonded to O at a top site. This specific atomic
      arrangement at the interface allows the cubic stacking to more effectively screen
      the substrate and film electric dipole moment than the hexagonal stacking, thus
      stabilizing the zinc blende phase even though the wurtzite phase is the ground
      state in the bulk.

PMID- 16090333
TI  - Creation of helical vortices during magnetization of aligned carbon nanotubes
      filled with Fe: theory and experiment.
AB  - We report a novel magnetic phenomenon consisting of the formation of helical spin
      configurations during the magnetization of densely packed ferromagnetic nanowires
      encapsulated inside carbon nanotubes. We studied the hysteresis loops when the
      magnetic fields are applied parallel and perpendicular to the nanotubes axes. We
      also performed theoretical calculations on aligned nanowire arrays that clearly
      indicate the creation of helical spin vortices in the hysteresis loops. The
      latter are caused by the presence of strong dipolar interactions among
      neighboring wires.

PMID- 16090334
TI  - Lateral motion of SiGe islands driven by surface-mediated alloying.
AB  - SiGe islands move laterally on a Si(001) substrate during in situ postgrowth
      annealing. This surprising behavior is revealed by an analysis of the substrate
      surface morphology after island removal using wet chemical etching. We explain
      the island motion by asymmetric surface-mediated alloying. Material leaves one
      side of the island by surface diffusion, and mixes with additional Si from the
      surrounding surface as it redeposits on the other side. Thus the island moves
      laterally while becoming larger and more dilute.

PMID- 16090335
TI  - Optical sum rules that relate to the potential energy of strongly correlated
      systems.
AB  - A class of sum rules for inelastic light scattering is developed. We show that
      the first moment of the nonresonant response provides information about the
      potential energy in strongly correlated systems. The polarization dependence of
      the sum rules provides information about the electronic excitations in different
      regions of the Brillouin zone. We determine the sum rule for the Falicov-Kimball
      model, which possesses a metal-insulator transition, and compare our results to
      the light scattering experiments in SmB(6).

PMID- 16090336
TI  - Full counting statistics for the Kondo dot.
AB  - The generating function for the cumulants of charge current distribution is
      calculated for two generalized Majorana resonant level models: the Kondo dot at
      the Toulouse point and the resonant level embedded in a Luttinger liquid with the
      interaction parameter g=1/2. We find that the low-temperature nonequilibrium
      transport in the Kondo case occurs via tunneling of physical electrons as well as
      by coherent transmission of electron pairs. We calculate the third cumulant
      ("skewness") explicitly and analyze it for different couplings, temperatures, and
      magnetic fields. For the g=1/2 setup the statistics simplifies and is given by a
      modified version of the Levitov-Lesovik formula.

PMID- 16090337
TI  - Heat transport as a probe of electron scattering by spin fluctuations: the case
      of antiferromagnetic CeRhIn(5).
AB  - Heat and charge conduction were measured in the heavy-fermion metal CeRhIn(5), an
      antiferromagnet with T(N)=3.8 K. The thermal resistivity is found to be
      proportional to the magnetic entropy, revealing that spin fluctuations are as
      effective in scattering electrons as they are in disordering local moments. The
      electrical resistivity, governed by a q(2) weighting of fluctuations, increases
      monotonically with temperature. In contrast, the difference between thermal and
      electrical resistivities, characterized by a omega(2) weighting, peaks sharply at
      T(N) and eventually goes to zero at a temperature T(*) approximately = 8 K. T(*)
      thus emerges as a measure of the characteristic energy of magnetic fluctuations.

PMID- 16090338
TI  - Shot noise in the chaotic-to-regular crossover regime.
AB  - We investigate the shot noise for phase-coherent quantum transport in the chaotic
      to-regular crossover regime. Employing the modular recursive Green's function
      method for both ballistic and disordered two-dimensional cavities, we find the
      Fano factor and the transmission eigenvalue distribution for regular systems to
      be surprisingly similar to those for chaotic systems. We argue that, in the case
      of regular dynamics in the cavity, diffraction at the lead openings is the
      dominant source of shot noise. We also explore the onset of the crossover from
      quantum-to-classical transport and develop a quasiclassical transport model for
      shot noise suppression which agrees with the numerical quantum data.

PMID- 16090339
TI  - Phase fluctuations in strongly coupled d-wave superconductors.
AB  - We present a numerically exact solution for the BCS Hamiltonian at any
      temperature, including the degrees of freedom associated with classical phase, as
      well as amplitude fluctuations via a Monte Carlo integration. This allows for an
      investigation over the whole range of couplings: from weak attraction, as in the
      well-known BCS limit, to the mainly unexplored strong-coupling regime of
      pronounced phase fluctuations. In the latter, two characteristic temperatures
      T(*) and T(c), associated with short- and long-range ordering, respectively, can
      be identified in a mean-field-motivated Hamiltonian. T(*) at the same time
      corresponds to the opening of a gap in the excitation spectrum. In addition to
      introducing a novel procedure to study strongly coupled d-wave superconductors,
      our results indicate that classical phase fluctuations are not sufficient to
      explain the pseudogap features of high-temperature superconductors.

PMID- 16090340
TI  - Specific heat measurement of the layered nitride superconductor Li(x)ZrNCl.
AB  - Specific heat has been investigated in a layered nitride superconductor,
      Li(0.12)ZrNCl, with T(c)=12.7 K. The obtained data have shown a marked dichotomy:
      The specific heat jump at T(c) (DeltaC/gamma(n)T(c)=1.8) and the superconducting
      gap ratio (2Delta/k(B)T(c)=4.6-5.2) have indicated an intermediate to a strong
      coupling of electrons, while the upper limit of the electron-phonon coupling
      constant lambda has directly been estimated to be 0.22, which belongs to a weak
      coupling regime. Furthermore, the rapid increase of gamma as a function of
      magnetic field suggests that the present material has an anisotropic s wave gap.

PMID- 16090341
TI  - Neel temperature of quasi-low-dimensional Heisenberg antiferromagnets.
AB  - The Neel temperature T(N) of quasi-one- and quasi-two-dimensional
      antiferromagnetic Heisenberg models on a cubic lattice is calculated by Monte
      Carlo simulations as a function of interchain (interlayer) to intrachain
      (intralayer) coupling J(')/J down to J(')/J approximately = 10(-3). We find that
      T(N) obeys a modified random-phase approximationlike relation for small J(')/J
      with an effective universal renormalized coordination number, independent of the
      size of the spin. Empirical formulas describing T(N) for a wide range of J(') and
      useful for the analysis of experimental measurements are presented.

PMID- 16090342
TI  - Vanishing magnetic interactions in ferromagnetic thin films.
AB  - We have used element-specific hysteresis measurements, based on the x-ray
      magnetic circular dichroism technique, to investigate magnetic trilayer
      structures composed of Fe and Ni layers. Within a critical regime we have
      discovered a class of structures in which the exchange interaction, the mechanism
      responsible for the macroscopic magnetism, can become vanishingly small. The
      experimental observations are supported by first principles theory and are
      explained as arising from a cancellation of several competing magnetic
      interactions. Hence, we have discovered a system with a novel exchange
      interaction between magnetic layers in direct contact that replaces the
      conventional exchange interaction in ferromagnets.

PMID- 16090343
TI  - Long-range frustration in a spin-glass model of the vertex-cover problem.
AB  - In a spin-glass system on a random graph, some vertices have their spins changing
      among different configurations of a ground-state domain. Long-range frustrations
      may exist among these unfrozen vertices in the sense that certain combinations of
      spin values for these vertices may never appear in any configuration of this
      domain. We present a mean field theory to tackle such long-range frustrations and
      apply it to the NP-hard minimum vertex-cover (hard-core gas condensation)
      problem. Our analytical results on the ground-state energy density and on the
      fraction of frozen vertices are in good agreement with known numerical and
      mathematical results.

PMID- 16090344
TI  - Quantitative analysis of magnetic excitations in Landau flux-closure structures
      using synchrotron-radiation microscopy.
AB  - We have measured the excitation spectrum of six micron magnetic squares using x
      ray magnetic circular dichroism. We observe all three excitations expected in a
      Landau flux-closure pattern. High temporal and spatial resolution allows
      quantitative analysis of the excitations. A short magnetic in plane pulse excites
      the magnetic element and we observe precessional motion of the magnetization
      within the domains as well as a domain wall mode and vortex motion. The vortex
      moves perpendicular to the excitation field and relaxes without showing a
      circulating orbit.

PMID- 16090345
TI  - Ferromagnetism driven by intrinsic point defects in HfO(2).
AB  - In view of recent experimental reports of unexpected ferromagnetism in HfO(2)
      thin films, we carried out first-principles investigations looking for magnetic
      order possibly brought about by the presence of small concentrations of intrinsic
      point defects. Ab initio electronic structure calculations using density
      functional theory show that isolated cation vacancy sites in HfO(2) lead to the
      formation of high-spin defect states. Furthermore these appear to be
      ferromagnetically coupled with a rather short range magnetic interaction,
      resulting in a ferromagnetic ground state for the whole system. More
      interestingly, the occurrence of these high-spin states and ferromagnetism is in
      the low symmetry monoclinic phase of HfO(2). This is radically different from
      other systems previously known to exhibit point defect ferromagnetism, warranting
      a closer look at the phenomenon.

PMID- 16090346
TI  - Interface double-exchange ferromagnetism in the Mn-Zn-O system: new class of
      biphase magnetism.
AB  - In this Letter, we experimentally show that the room temperature ferromagnetism
      in the Mn-Zn-O system recently observed is associated with the coexistence of
      Mn(3+) and Mn(4+) via a double-exchange mechanism. The presence of the ZnO around
      MnO(2) modifies the kinetics of MnO(2)-->Mn(2)O(3) reduction and favors the
      coexistence of both Mn oxidation states. The ferromagnetic phase is associated
      with the interface formed at the Zn diffusion front into Mn oxide, corroborated
      by preparing thin film multilayers that exhibit saturation magnetization 2 orders
      of magnitude higher than bulk samples.

PMID- 16090347
TI  - Midgap states in antiferromagnetic Heisenberg chains with a staggered field.
AB  - We study low-energy excitations in antiferromagnetic Heisenberg chains with a
      staggered field which splits the spectrum into a longitudinal and a transverse
      branch. Bound states are found to exist inside the field induced gap in both
      branches. They originate from the edge effects and are inherent to spin-chain
      materials. The sine-Gordon scaling h(2/3)(s)[log(h(s)](1/6) (h(s), the staggered
      field) provides an accurate description for the gap and midgap energies in the
      transverse branch for S=1/2 and the midgap energies in both branches for S=3/2
      over a wide range of magnetic field; however, it can fit other low-energy
      excitations only at much lower field. Moreover, the integer-spin S=1 chain
      displays scaling behavior that does not fit this scaling law. These results
      reveal intriguing features of magnetic excitations in spin-chain materials that
      deserve further investigation.

PMID- 16090348
TI  - Surface-enhanced plasmon splitting in a liquid-crystal-coated gold nanoparticle.
AB  - We show that, when a gold nanoparticle is coated by a thin layer of nematic
      liquid crystal, the nanoparticle surface has a strong effect on the director
      orientation, but, surprisingly, this deformation can enhance the surface plasmon
      splitting. We consider three plausible liquid crystal director configurations in
      zero electric field: boojum pair (north-south pole configuration), baseball
      (tetrahedral), and homogeneous. From the discrete dipole approximation, we find
      that the surface plasmon splitting is largest for the boojum pair, and this
      result is in good agreement with experiment.

PMID- 16090349
TI  - Bonding in the superionic phase of water.
AB  - The predicted superionic phase of water is investigated via ab initio molecular
      dynamics at densities of 2.0--3.0 g/cc (34-115 GPa) along the 2000 K isotherm. We
      find that extremely rapid (superionic) diffusion of protons occurs in a fluid
      phase at pressures between 34 and 58 GPa. A transition to a stable body-centered
      cubic O lattice with superionic proton conductivity is observed between 70 and 75
      GPa, a much higher pressure than suggested in prior work. We find that all
      molecular species at pressures greater than 75 GPa are too short lived to be
      classified as bound states. Up to 95 GPa, we find a solid superionic phase
      characterized by covalent O-H bonding. Above 95 GPa, a transient network phase is
      found characterized by symmetric O-H hydrogen bonding with nearly 50% covalent
      character. In addition, we describe a metastable superionic phase with quenched O
      disorder.

PMID- 16090350
TI  - How the liquid-liquid transition affects hydrophobic hydration in deeply
      supercooled water.
AB  - We determine the phase diagram of liquid supercooled water by extensive computer
      simulations using the TIP5P-E model. We find that the transformation of water
      into a low density liquid in the supercooled range strongly enhances the
      solubility of hydrophobic particles. The transformation of water into a
      tetrahedrally structured liquid is accompanied by a minimum in the hydration
      entropy and enthalpy. The corresponding change in sign of the solvation heat
      capacity indicates a loss of one characteristic signature of hydrophobic
      hydration. The observed behavior is found to be qualitatively in accordance with
      the predictions of the information theory model of Garde et al.

PMID- 16090351
TI  - Stratification kinetics of polyelectrolyte solutions confined in thin films.
AB  - We have studied free horizontal liquid films made with semidilute polyelectrolyte
      solutions. A stratification phenomenon is observed during film thinning, with a
      step size close to the mesh size of the polymer network: dark domains nucleate
      and expand, the outer polymer layer dewetting a thinner film. The kinetics of
      dark spot expansion is not simply related to bulk viscosity and becomes faster
      when the film thickness decreases, suggesting an increase of the chain mobility
      of the confined polymer chains. These findings are similar to recent ones for
      other confined liquids and are the first reported so far for freely standing
      films.

PMID- 16090352
TI  - Langevin trajectories between fixed concentrations.
AB  - We consider the trajectories of particles diffusing between two infinite baths of
      fixed concentrations connected by a channel, e.g., a protein channel of a
      biological membrane. The steady state influx and efflux of Langevin trajectories
      at the boundaries of a finite volume containing the channel and parts of the two
      baths is replicated by termination of outgoing trajectories and injection
      according to a residual phase space density. We present a simulation scheme that
      maintains averaged fixed concentrations without creating spurious boundary
      layers, consistent with the assumed physics.

PMID- 16090353
TI  - Predator-prey cycles from resonant amplification of demographic stochasticity.
AB  - We present the simplest individual level model of predator-prey dynamics and
      show, via direct calculation, that it exhibits cycling behavior. The
      deterministic analogue of our model, recovered when the number of individuals is
      infinitely large, is the Volterra system (with density-dependent prey
      reproduction) which is well known to fail to predict cycles. This difference in
      behavior can be traced to a resonant amplification of demographic fluctuations
      which disappears only when the number of individuals is strictly infinite. Our
      results indicate that additional biological mechanisms, such as predator
      satiation, may not be necessary to explain observed predator-prey cycles in real
      (finite) populations.

PMID- 16090354
TI  - Interference microscopy under double-wavelet analysis: a new approach to studying
      cell dynamics.
AB  - This Letter combines a novel experimental approach to the study of intracellular
      processes with a newly developed technique for multimode time-series analysis.
      Experiments are performed on isolated pond snail (Lymnaea stagnalis) neurons.
      Local variations in the cellular refractive index as detected by laser
      interference microscopy are related to the processes in the cell. A wavelet
      analysis shows the presence of several identifiable modes in the membrane and
      intracellular dynamics, and a double-wavelet analysis reveals nonlinear
      interactions between the regulatory processes in the form of mutual frequency and
      amplitude modulations.

PMID- 16090355
TI  - Model for reversible colloidal gelation.
AB  - We report a numerical study, covering a wide range of packing fraction Phi and
      temperature T, for a system of particles interacting via a square well potential
      supplemented by an additional constraint on the maximum number n(max) of bonded
      interactions. We show that, when n(max)<6, the liquid-gas coexistence region
      shrinks, giving access to regions of low Phi where dynamics can be followed down
      to low T without an intervening phase separation. We characterize these arrested
      states at low densities (gel states) in terms of structure and dynamical slowing
      down, pointing out features which are very different from the standard glassy
      states observed at high Phi values.

PMID- 16090356
TI  - Gravitational collapse of colloidal gels.
AB  - We present a unified framework for understanding the compaction of colloidal gels
      under their own weight. The dynamics of the collapse are determined by the value
      of the gravitational stress sigma(g), as compared to the yield stress sigma(Y) of
      the network. For sigma(g)<sigma(Y), gels collapse poroelastically, and their rate
      of compression decays exponentially in time. For sigma(g)>sigma(Y), the network
      eventually yields, leading to rapid settling. In both cases, the rate of collapse
      is backflow limited, while its overall magnitude is determined by a balance
      between gravitational stress and network elastic stress.

PMID- 16090357
TI  - Synchronization is enhanced in weighted complex networks.
AB  - The propensity for synchronization of complex networks with directed and weighted
      links is considered. We show that a weighting procedure based upon the global
      structure of network pathways enhances complete synchronization of identical
      dynamical units in scale-free networks. Furthermore, we numerically show that
      very similar conditions hold also for phase synchronization of nonidentical
      chaotic oscillators.

PMID- 16090358
TI  - Canalizing Kauffman networks: nonergodicity and its effect on their critical
      behavior.
AB  - Boolean networks have been used to study numerous phenomena, including gene
      regulation, neural networks, social interactions, and biological evolution. Here,
      we propose a general method for determining the critical behavior of Boolean
      systems built from arbitrary ensembles of Boolean functions. In particular, we
      solve the critical condition for systems of units operating according to
      canalizing functions and present strong numerical evidence that our approach
      correctly predicts the phase transition from order to chaos in such systems.

PMID- 16090359
TI  - Comment on "Estimating model parameters from time series by autosynchronization".

PMID- 16090360
TI  - Comment on "Shadowability of statistical averages in chaotic systems".

PMID- 16090362
TI  - Comment on "Normal heat conductivity of the one-dimensional lattice with periodic
      potential of nearest-neighbor interaction".

PMID- 16090364
TI  - Comment on "Quantum confinement and electronic properties of silicon nanowires".

PMID- 16090366
TI  - Comment on "Effects of point defects on the phase diagram of vortex states in
      high-T(c) superconductors in the B//c Axis".

PMID- 16090368
TI  - Ion trap simulations of quantum fields in an expanding universe.
AB  - We propose an experiment in which the phonon excitation of ion(s) in a trap, with
      a trap frequency exponentially modulated at rate kappa, exhibits a thermal
      spectrum with an "Unruh" temperature given by k(B)T=Planck kappa. We discuss the
      similarities of this experiment to the response of detectors in a de Sitter
      universe and the usual Unruh effect for uniformly accelerated detectors. We
      demonstrate a new Unruh effect for detectors that respond to antinormally ordered
      moments using the ion's first blue sideband transition.

PMID- 16090369
TI  - Deconfinement and phase diagram of bosons in a linear optical lattice with a
      particle reservoir.
AB  - We investigate the zero-temperature phases of bosons in a one-dimensional optical
      lattice with an explicit tunnel coupling to a Bose-condensed particle reservoir.
      Renormalization group analysis of this system is shown to reveal three phases:
      one in which the linear system is fully phase locked to the reservoir; one in
      which Josephson vortices between the one-dimensional system and the particle
      reservoir deconfine due to quantum fluctuations, leading to a decoupled state in
      which the one-dimensional system is metallic; and one in which the one
      dimensional system is in a Mott insulating state.

PMID- 16090370
TI  - Simulating maximal quantum entanglement without communication.
AB  - It is known that all causal correlations between two parties which output each 1
      bit, a and b, when receiving each 1 bit, x and y, can be expressed as convex
      combinations of local correlations (i.e., correlations that can be simulated with
      local random variables) and nonlocal correlations of the form a+b=xy mod 2. We
      show that a single instance of the latter elementary nonlocal correlation
      suffices to simulate exactly all possible projective measurements that can be
      performed on a maximally entangled state of two qubits, with no communication
      needed at all. This elementary nonlocal correlation thus defines some unit of
      nonlocality, which we call a nl bit.

PMID- 16090371
TI  - Photonic band gap via quantum coherence in vortex lattices of Bose-Einstein
      condensates.
AB  - We investigate the optical response of an atomic Bose-Einstein condensate with a
      vortex lattice. We find that it is possible for the vortex lattice to act as a
      photonic crystal and create photonic band gaps, by enhancing the refractive index
      of the condensate via a quantum coherent scheme. If high enough index contrast
      between the vortex core and the atomic sample is achieved, a photonic band gap
      arises depending on the healing length and the lattice spacing. A wide range of
      experimentally accessible parameters are examined and band gaps in the visible
      region of the electromagnetic spectrum are found. We also show how directional
      band gaps can be used to directly measure the rotation frequency of the
      condensate.

PMID- 16090372
TI  - Measurement of quantum weak values of photon polarization.
AB  - We experimentally determine weak values for a single photon's polarization,
      obtained via a weak measurement that employs a two-photon entangling operation,
      and postselection. The weak values cannot be explained by a semiclassical wave
      theory, due to the two-photon entanglement. We observe the variation in the size
      of the weak value with measurement strength, obtaining an average measurement of
      the S1 Stokes parameter more than an order of magnitude outside of the operator's
      spectrum for the smallest measurement strengths.

PMID- 16090373
TI  - Demonstrating superior discrimination of locally prepared states using nonlocal
      measurements.
AB  - We experimentally demonstrate the superior discrimination of separated,
      unentangled two-qubit correlated states using nonlocal measurements, when
      compared with measurements based on local operations and classical
      communications. When predicted theoretically, this phenomenon was dubbed "quantum
      nonlocality without entanglement." We characterize the performance of the
      nonlocal, or joint, measurement with a payoff function, for which we measure 0.72
      +/- 0.02, compared with the maximum locally achievable value of 2/3 and the
      overall optimal value of 0.75.

PMID- 16090374
TI  - Pixel entanglement: experimental realization of optically entangled d=3 and d=6
      qudits.
AB  - We demonstrate a simple experimental method for creating entangled qudits. Using
      transverse-momentum and position entanglement of photons emitted in spontaneous
      parametric down-conversion, we show entanglement between discrete regions of
      space, i.e., pixels. We map each photon onto as many as six pixels, where each
      pixel represents one level of our qudit state. The method is easily generalizable
      to create even higher dimensional, entangled states. Thus, the realization of
      quantum information processing in arbitrarily high dimensions is possible,
      allowing for greatly increased information capacity.

PMID- 16090375
TI  - High-fidelity teleportation beyond the no-cloning limit and entanglement swapping
      for continuous variables.
AB  - We experimentally demonstrate continuous-variable quantum teleportation beyond
      the no-cloning limit. We teleport a coherent state and achieve the fidelity of
      0.70 +/- 0.02 that surpasses the no-cloning limit of 2/3. Surpassing the limit is
      necessary to transfer the nonclassicality of an input quantum state. By using our
      high-fidelity teleporter, we demonstrate entanglement swapping, namely,
      teleportation of quantum entanglement, as an example of transfer of
      nonclassicality.

PMID- 16090376
TI  - Propulsion of a molecular machine by asymmetric distribution of reaction
      products.
AB  - A simple model for the reaction-driven propulsion of a small device is proposed
      as a model for (part of) a molecular machine in aqueous media. The motion of the
      device is driven by an asymmetric distribution of reaction products. The
      propulsive velocity of the device is calculated as well as the scale of the
      velocity fluctuations. The effects of hydrodynamic flow as well as a number of
      different scenarios for the kinetics of the reaction are addressed.

PMID- 16090377
TI  - Gravitational radiation reaction and inspiral waveforms in the adiabatic limit.
AB  - We describe progress evolving an important limit of binaries in general
      relativity: stellar mass compact objects spiraling into much larger black holes.
      Such systems are of great observational interest. We have developed tools to
      compute for the first time the radiation from generic orbits. Using global
      conservation laws, we find the orbital evolution and waveforms for special cases.
      For generic orbits, inspirals and waveforms can be found by augmenting our
      approach with an adiabatic self-force rule due to Mino. Such waveforms should be
      accurate enough for gravitational-wave searches.

PMID- 16090378
TI  - Designer gravity and field theory effective potentials.
AB  - Motivated by the anti-de Sitter conformal field theory correspondence, we show
      that there is remarkable agreement between static supergravity solutions and
      extrema of a field theory potential. For essentially any function V(alpha) there
      are boundary conditions in anti-de Sitter space so that gravitational solitons
      exist precisely at the extrema of V and have masses given by the value of V at
      these extrema. Based on this, we propose new positive energy conjectures. On the
      field theory side, each function V can be interpreted as the effective potential
      for a certain operator in the dual field theory.

PMID- 16090379
TI  - Quantum gravity and Lorentz invariance violation in the standard model.
AB  - The most important problem of fundamental physics is the quantization of the
      gravitational field. A main difficulty is the lack of available experimental
      tests that discriminate among the theories proposed to quantize gravity.
      Recently, Lorentz invariance violation by quantum gravity (QG) has been the
      source of growing interest. However, the predictions depend on an ad hoc
      hypothesis and too many arbitrary parameters. Here we show that the standard
      model itself contains tiny Lorentz invariance violation terms coming from QG. All
      terms depend on one arbitrary parameter alpha that sets the scale of QG effects.
      This parameter can be estimated using data from the ultrahigh energy cosmic ray
      spectrum to be |alpha|< approximately 10(-22)-10(-23).

PMID- 16090380
TI  - Effects of a decaying cosmological fluctuation.
AB  - We present the initial conditions for a decaying cosmological perturbation and
      study its signatures in the cosmic microwave background anisotropies and matter
      power spectra. An adiabatic decaying mode in the presence of components that are
      not described as perfect fluids (such as collisionless matter) decays slower than
      in a perfect-fluid dominated Universe and displays super-Hubble oscillations.
      Wilkinson Microwave Anisotropy Probe first year data constrain the decaying to
      growing ratio of scale invariant adiabatic fluctuations at the matter-radiation
      equality to less than 10%.

PMID- 16090382
TI  - Scales of mass generation for quarks, leptons, and majorana neutrinos.
AB  - We study 2-->n inelastic fermion-(anti)fermion scattering into multiple
      longitudinal weak gauge bosons and derive universal upper bounds on the scales of
      fermion mass generation by imposing unitarity of the S matrix. We place new upper
      limits on the scales of fermion mass generation, independent of the electroweak
      symmetry breaking scale. Strikingly, we find that the strongest 2-->n limits fall
      in a narrow range, 3-170 TeV (with n=2-24), depending on the observed fermion
      masses.

PMID- 16090386
TI  - Quantum electrodynamics in strong electric fields: the ground-state Lamb shift in
      hydrogenlike uranium.
AB  - X-ray spectra following radiative recombination of free electrons with bare
      uranium ions (U92+) were measured at the electron cooler of the ESR storage ring.
      The most intense lines observed in the spectra can be attributed to the
      characteristic Lyman ground-state transitions and to the recombination of free
      electrons into the K shell of the ions. Our experiment was carried out by
      utilizing the deceleration technique which leads to a considerable reduction of
      the uncertainties associated with Doppler corrections. This, in combination with
      the 0 degree observation geometry, allowed us to determine the ground-state Lamb
      shift in hydrogenlike uranium (U91+) from the observed x-ray lines with an
      accuracy of 1%. The present result is about 3 times more precise than the most
      accurate value available up to now and provides the most stringent test of bound
      state quantum electrodynamics for one-electron systems in the strong-field
      regime.

PMID- 16090387
TI  - Photoionization of synchrotron-radiation-excited atoms: separating partial cross
      sections by full polarization control.
AB  - Resonant atomic excitation by synchrotron radiation and subsequent ionization by
      a tunable dye laser is used to study the photoionization of short-lived Rydberg
      states in Xe. By combining circular and linear polarization of the synchrotron as
      well as of the laser photons the partial photoionization cross sections were
      separated in the region of overlapping autoionizing resonances of different
      symmetry and the parameters of the resonances were extracted.

PMID- 16090384
TI  - Measurement of polarization and triple-product correlations in B-->phiK* decays.
AB  - We present measurements of decay amplitudes and triple-product correlations in B-
      >phiK* decays based on 253 fb(-1) of data recorded at the Upsilon(4S) resonance
      with the Belle detector at the KEKB e(+)e(-) storage ring. The decay amplitudes
      for the three different helicity states are determined from the angular
      distributions of final-state particles. The longitudinal polarization amplitudes
      are found to be 0.45 +/- 0.05 +/- 0.02 for B0-->phiK(*0) and 0.52 +/- 0.08 +/-
      0.03 for B+ -->phiK(*+) decays. CP- and T-odd CP-violating triple-product
      asymmetries are measured to be consistent with zero.

PMID- 16090388
TI  - Experimental and theoretical evidence for long-lived molecular hydrogen anions H2
      and D2-.
AB  - The existence of (metastable) molecular hydrogen anions H2(-), D2(-), and H3(-)
      is demonstrated. These anion species were produced by sputtering of TiH2 and TiD2
      targets with Cs+ ions and were identified by accelerator mass spectrometry. From
      the respective flight times through the spectrometer, lifetimes for H2(-) and D2(
      ) of at least 3 micros and 4 micros, respectively, can be inferred. Theoretical
      calculations within the nonlocal resonance model predict the existence of highly
      rotationally excited anions with lifetimes in the micros range. It is proposed
      that in sputtering molecular hydrogen species with high rotational and
      vibrational excitation are formed that are stable on the time scale of the
      experiment.

PMID- 16090389
TI  - Collisional properties of cold spin-polarized metastable neon atoms.
AB  - We measure the rates of elastic and inelastic two-body collisions of cold spin
      polarized neon atoms in the metastable 3P2 state for 20Ne and 22Ne in a magnetic
      trap. From particle loss, we determine the loss parameter of inelastic collisions
      beta=6.5(18) x 10(-12) cm(3) s(-1) for 20Ne and beta=1.2(3) x 10(-11) cm(3) s(-1)
      for 22Ne. These losses are caused by ionizing (i.e., Penning) collisions and
      occur less frequently than for unpolarized atoms. This proves the suppression of
      Penning ionization due to spin polarization. From cross-dimensional relaxation
      measurements, we obtain elastic scattering lengths of a=-180(40)a(0) for 20Ne and
      a = +150(+80)(-50)a(0) for 22Ne, where a(0)=0.0529 nm.

PMID- 16090385
TI  - Observation of the D1(2420)-->Dpi + pi- decays.
AB  - We report on the first observation of D0/1(2420)-->D0pi- pi+ and D+/1(2420-->D+
      pi- pi+ decays (where the contribution from the dominant known D1-->D*pi decay
      mode is excluded) in the B- -->D0/1pi-) and (-)B0-->D+/1pi- decays, respectively.
      The observation is based on 15.2 x 10(7) B(-)B events collected with the Belle
      detector at the KEKB collider. We also set 90% confidence level upper limits for
      the branching fractions of the four following decays: B- -->D0/1pi-, D01-
      >D(*0)pi- pi+, (-)B0-->D+/1pi-, D+/1-->D(*+) pi- pi+, B- -->D(*0)2(2460)pi-,
      D(*0)2 -->D(*0) pi- pi+, (-)B0-->D(*+)2(2460)pi-, D(*+)2-->D(*+)pi- pi+.

PMID- 16090391
TI  - Tuning the continuum ground state energy of NO2- 2 by water molecules.
AB  - Electron scattering on NO-2, NO-2 x (H2O), and NO-2 x (H2O)(2) was performed in
      two storage rings. We confirm the presence of earlier reported NO2-2 dianion
      resonances and show that they remain when water is attached. Importantly,
      hydration tunes the energy: each water molecule lowers the ground state energy by
      0.8 +/- 0.3 eV relative to the monoanion. NO2-2 is observed to decay by two
      electron emission, possibly in combination with fragmentation. NO(2-)2 x (H2O)
      mainly decays into NO-2 + H2O + e(-).

PMID- 16090390
TI  - Atom interferometric detection of the pairing order parameter in a Fermi gas.
AB  - We propose two interferometric schemes to experimentally detect in real space the
      onset of pair condensation in a two-spin-component Fermi gas. Two atomic wave
      packets are coherently extracted from the gas at different positions and are
      mixed by a matter-wave beam splitter: we show that the spatial long-range order
      of the atomic pairs in the gas reflects in the atom counting statistics in the
      beam splitter output channels. The same long-range order is also shown to create
      a matter-wave grating in the overlapping region of the two extracted wave
      packets, grating that can be revealed by a light-scattering experiment.

PMID- 16090392
TI  - Proof that the hydrogen-antihydrogen molecule is unstable.
AB  - In the framework of nonrelativistic quantum mechanics we derive a necessary
      condition for four Coulomb charges (m1(+), m2(-), m3(+), m4(-)), where all masses
      are assumed finite, to form the stable system. The obtained stability condition
      is physical and is expressed through the required minimal ratio of Jacobi masses.
      In particular, this provides the rigorous proof that hydrogen-antihydrogen and
      muonium-antimuonium molecules and hydrogen-positron-muon systems are unstable. It
      also proves that replacing hydrogen in the hydrogen-antihydrogen molecule with
      its heavier isotopes does not make the molecule stable. These are the first
      rigorous results on the instability of these systems.

PMID- 16090393
TI  - Wolf equations for two-photon light.
AB  - The spatiotemporal two-photon probability amplitude that describes light in a two
      photon entangled state obeys equations identical to the Wolf equations, which are
      satisfied by the mutual coherence function for light in any quantum state. Both
      functions therefore propagate similarly through optical systems. A generalized
      van Cittert-Zernike theorem explains the predicted enhancement in resolution for
      entangled-photon microscopy and quantum lithography. The Wolf equations provide a
      particularly powerful analytical tool for studying three-dimensional imaging and
      lithography since they describe propagation in continuous inhomogeneous media.

PMID- 16090381
TI  - Measurement of dijet azimuthal decorrelations at central rapidities in pp
      collisions at sqrt s =1.96 TeV.
AB  - Correlations in the azimuthal angle between the two largest transverse momentum
      jets have been measured using the D0 detector in p (-)p collisions at a center-of
      mass energy sqrt[s]=1.96 TeV. The analysis is based on an inclusive dijet event
      sample in the central rapidity region corresponding to an integrated luminosity
      of 150 pb(-1). Azimuthal correlations are stronger at larger transverse momenta.
      These are well described in perturbative QCD at next-to-leading order in the
      strong coupling constant, except at large azimuthal differences where
      contributions with low transverse momentum are significant.

PMID- 16090394
TI  - Indistinguishable photons from a single molecule.
AB  - We report the results of coincidence counting experiments at the output, of a
      Michelson interferometer using the zero-phonon-line emission of a single molecule
      at 1.4 K. Under continuous wave excitation, we observe the absence of coincidence
      counts as an indication of two-photon interference. This corresponds to the
      observation of Hong-Ou-Mandel correlations and proves the suitability of the zero
      phonon-line emission of single molecules for applications in linear optics
      quantum computation.

PMID- 16090395
TI  - Spatially noiseless optical amplification of images.
AB  - We present the first experimental demonstration of noiseless amplification of
      images, where noise refers to spatial quantum fluctuations on the pixels of
      single shot images. Phase-sensitive and phase-insensitive schemes are compared
      and the noise figures are in good agreement with theory, inasmuch this theory
      includes the quantum efficiency of the whole system and the pixel size.

PMID- 16090396
TI  - Measurement of net group and reshaping delays for optical pulses in dispersive
      media.
AB  - We experimentally demonstrate the direct measurement of net group and reshaping
      delays for arbitrary optical pulses in dispersive media, verifying the earlier
      prediction of Peatross et al. [Phys. Rev. Lett. 84, 2370 (2000)]. Incoherent
      pulse propagation in an absorptionless system is well described by net group
      delay; even the medium causes a great deal of deformation in the transmitted
      pulse. However, in the case of phase modulated chirping pulses in a resonant
      absorber, the so-called superluminal or subluminal propagation velocity is
      strongly influenced by the reshaping delay.

PMID- 16090397
TI  - Temporal behavior of radiation-pressure-induced vibrations of an optical
      microcavity phonon mode.
AB  - We analyze experimentally and theoretically mechanical oscillation within an
      optical cavity stimulated by the pressure of circulating optical radiation. The
      resulting radio frequency cavity vibrations (phonon mode) cause modulation of the
      incident, continuous-wave (cw) input pump beam. Furthermore, with increasing cw
      pump power, an evolution from sinusoidal modulation to random oscillations is
      observed in the pump power coupled from the resonator. The temporal evolution
      with pump power is studied, and agreement was found with theory. In addition to
      applications in quantum optomechanics, the present work suggests that radiation
      pressure-induced effects can establish a practical limit for the miniaturization
      of optical silica microcavities.

PMID- 16090398
TI  - Controlled observation of a nonequilibrium Ising-Bloch transition in a nonlinear
      optical cavity.
AB  - We report the controlled observation of the nonequilibrium Ising-Bloch transition
      in a broad area nonlinear optical cavity (a quasi-1D single longitudinal-mode
      photorefractive oscillator in a degenerate four-wave mixing configuration). Our
      experimental technique allows for the controlled injection of the domain walls.
      We use cavity detuning as control parameter and find that both Ising and Bloch
      walls can exist for the same detuning values within a certain interval of
      detunings; i.e., the Ising-Bloch transition is hysteretic in our case. A complex
      Ginzburg-Landau model is used for supporting the observations.

PMID- 16090383
TI  - Search for decays of B0-->e+ e-, B0-->mu+ mu-, B0-->e +/- mu-/+.
AB  - We present a search for the decays B0-->e+ e-, B0-->mu+ mu-, and B0-->e (+/-) mu
      (-/+) in data collected at the Upsilon(4S) resonance with the BABAR detector at
      the SLAC B Factory. Using a data set of 111 fb(-1), we find no evidence for a
      signal in any of the three channels investigated and set the following branching
      fraction upper limits at the 90% confidence level: B(B0-->e+ e-) < 6.1 x 10(-8),
      B(B0-->mu+ mu-) < 8.3 x 10(-8), and B(B0-->e (+/-) mu (-/+) )<18 x 10(-8).

PMID- 16090399
TI  - Self-organization of two-dimensional waves in an active dispersive-dissipative
      nonlinear medium.
AB  - We consider the pattern-formation dynamics of a two-dimensional (2D) nonlinear
      evolution equation that includes the effects of instability, dissipation, and
      dispersion. We construct 2D stationary solitary pulse solutions of this equation,
      and we develop a coherent structures theory that describes the weak interaction
      of these pulses. We show that in the strongly dispersive case, 2D pulses organize
      themselves into V shapes. Our theoretical findings are in good agreement with
      time-dependent computations of the fully nonlinear system.

PMID- 16090400
TI  - Inelastic gravitational billiards.
AB  - We present an experimental investigation of gravitational billiards where the
      particle undergoes inelastic collisions with its boundary. The motion is mapped
      for an inelastic particle contained within parabolic, wedge, and hyperbolic
      boundaries. For the parabola, stable orbits are found and the wedge demonstrates
      a characteristic instability for its vertex angle. In the instance of the
      hyperbola, there are several features of the dynamics similar to the parabola at
      low driving and the wedge for higher driving. However, the low driving case for a
      hyperbola can only be completely understood by considering inelasticity effects
      predicted by a numerical simulation and the observation that the velocity
      dependent inelasticity allows the particle to sample several nearby trajectories
      for fixed driving.

PMID- 16090401
TI  - Universality and hysteretic dynamics in rapid fracture.
AB  - Experiments in the dynamic fracture of brittle polyacrylamide gels show that a
      single-crack state undergoes a hysteretic transition to the microbranching
      instability with a characteristic activation time. Quantitative measurements also
      indicate that features such as crack front inertia, self-focusing of
      microbranches, and the appearance of front waves are universal attributes of
      dynamic fracture.

PMID- 16090402
TI  - Asymptotic behavior of the Rayleigh-Taylor instability.
AB  - We investigate long time numerical simulations of the inviscid Rayleigh-Taylor
      instability at Atwood number one using a boundary integral method. We are able to
      attain the asymptotic behavior for the spikes predicted by Clavin and Williams
      for which we give a simplified demonstration. In particular, we observe that the
      spike's curvature evolves as t(3), while the overshoot in acceleration shows good
      agreement with the suggested 1/t(5) law. Moreover, we obtain consistent results
      for the prefactor coefficients of the asymptotic laws. Eventually we exhibit the
      self-similar behavior of the interface profile near the spike.

PMID- 16090403
TI  - Effective conductivity of heterogeneous multiphase media with circular
      inclusions.
AB  - Determining the effective conductivity of heterogeneous media is a central
      problem in different fields of physics. The medium considered here contains
      cylinders (inclusions) of random conductivities that are distributed at random in
      an embedding matrix. For random systems, widely encountered in applications, we
      derive an approximative analytical solution that applies to significantly denser
      configurations than Maxwell first-order approximations. The analytic solution is
      tested against accurate numerical simulations. The widely used effective medium
      approach is shown to be exact for symmetric conductivity distributions and quite
      accurate for asymmetrical cases.

PMID- 16090404
TI  - Edge-localized-mode--induced transport of impurity density, energy, and momentum.
AB  - High temporal and spatial resolution measurements of impurity dynamics associated
      with an edge-localized mode (ELM) indicate that the ELM perturbation consists of
      two distinct parts: a rapid (< 300 micros) expulsion of impurity density at the
      time of the instability followed by a slower time scale (< 1 ms) decrease in the
      ion temperature. While the density perturbation remains nearly constant over a
      wide range of plasma collisionality, the temperature perturbation decreases as
      the collisionality increases. Analysis of the radial electric field E(r)
      evolution indicates that the E(r) well normally present in H-mode plasmas is
      modified strongly by the ELM and that the size of the temperature perturbation is
      correlated with the associated change in the E x B shear.

PMID- 16090405
TI  - Onset of turbulence and profile resilience in the Helimak configuration.
AB  - An experimental study of the onset of drift wave and flute interchange
      instabilities in the Helimak configuration is presented. It is shown that the
      Helimak offers the opportunity to separate the regions where these instabilities
      are active and to assess their relative role in cross-field anomalous transport
      and in the self-organization of exponential plasma density profiles with
      resilient scale length. Some results indicating a period doubling route to
      turbulence are also presented.

PMID- 16090406
TI  - Direct experimental evidence for current-transfer mode operation of nested
      tungsten wire arrays at 16-19 MA.
AB  - Nested tungsten wire arrays (20-mm on 12-mm diam.) are shown for the first time
      to operate in a current-transfer mode at 16-19 MA, even for azimuthal interwire
      gaps of 0.2 mm that are the smallest typically used for any array experiment.
      After current transfer, the inner wire array shows discrete wire ablation and
      implosion characteristics identical to that of a single array, such as axially
      nonuniform ablation, delayed acceleration, and trailing mass and current. The
      presence of trailing mass from the outer and the inner arrays may play a role in
      determining nested array performance.

PMID- 16090407
TI  - Force-free magnetic relaxation in driven plasmas.
AB  - Taylor relaxation in a driven plasma with normal magnetic field intercepting the
      boundary is described by the Jensen-Chu theory, which predicts infinite energy
      and helicity barriers that constrain the accessible relaxed states to system
      scale. For a partially relaxed force-free (j=kB) plasma where k is a field line
      constant, nonlinearity regularizes the Jensen-Chu singularities and new branches
      of relaxed state become accessible, such as the flipped spheromak and other high
      k states.

PMID- 16090408
TI  - Excitation of toroidicity-induced Alfven eigenmodes by the electrodes inserted in
      a heliotron/torsatron plasma.
AB  - A novel method of exciting shear Alfven waves using electrodes inserted in a
      plasma was developed for basic study of Alfven eigenmodes in a
      heliotron/torsatron plasma. The electrodes can induce excitation current along
      the confinement field line, and generate magnetic perturbations perpendicular to
      the confinement field. By sweeping the frequency of the current in a cold plasma,
      the toroidicity-induced Alfven eigenmode was resonantly excited at the predicted
      frequency and radial location. Plasma response to the applied magnetic
      perturbations indicates a fairly large damping rate caused by continuum damping.

PMID- 16090409
TI  - Universal transition state for high-pressure zinc blende to rocksalt phase
      transitions.
AB  - First-principles density functional calculations show that the high-pressure
      transitions of different semiconductors from zinc blende to rocksalt go through a
      transition state, which is universal in the sense that its position along the
      path and the corresponding geometry is independent of the chemical components of
      the semiconductor. This is explained using a Landau-like model expansion of the
      free energy in cosine functions of atomic position.

PMID- 16090410
TI  - Nonlocal screening, electron-phonon coupling, and phonon renormalization in
      metals.
AB  - A method for calculating the phonon self-energy in metals arising from the
      coupling between phonons and electrons near the Fermi surface is developed. The
      essence of this scheme is the separation of the inter- and intraband parts of the
      electron polarizability. The intraband contribution provides extra screenings and
      is closely related to the electron-phonon coupling and phonon softening in
      metals. Applications of this scheme to phonons in MgB2 give excellent results
      when compared with experiments and previous theoretical work. In addition, both
      electron and hole dopings are found to reduce the renormalization effect of the
      E(2g) phonon mode, which indicates a weakened electron-phonon coupling in the
      doped systems.

PMID- 16090411
TI  - Near-field intensity correlations in semicontinuous metal-dielectric films.
AB  - Spatial intensity correlation functions are obtained from near-field scanning
      optical microscope measurements of semicontinuous metal-dielectric films. The
      concentration of metal particles on a dielectric surface is varied over a wide
      range to control the scattering strength. At low and high metal coverages where
      scattering is weak, the intensity correlation functions exhibit oscillations in
      the direction of incident light due to excitation of propagating surface waves.
      In the intermediate regime of metal concentration, the oscillatory behavior is
      replaced by a monotonic decay as a result of strong scattering and anomalous
      absorption. Significant differences in the near-field intensity correlations
      between metallic and dielectric random systems are demonstrated.

PMID- 16090412
TI  - Kinetic step bunching instability during surface growth.
AB  - We study the step bunching kinetic instability in a growing crystal surface
      characterized by anisotropic diffusion. The instability is due to the interplay
      between the elastic interactions and the alternation of step parameters. This
      instability is predicted to occur on a vicinal semiconductor surface Si(001) or
      Ge(001) during epitaxial growth. The maximal growth rate of the step bunching
      increases like F4, where F is the deposition flux. Our results are complemented
      with numerical simulations which reveal a coarsening behavior in the long time
      evolution for the nonlinear step dynamics.

PMID- 16090413
TI  - Dynamic ad-dimer twisting assisted nanowire self-assembly on Si(001).
AB  - Based on ab initio total energy calculation, we show that a dynamic ad-dimer
      twisting assisted (DATA) process plays a crucial role in facilitating a novel
      structural reconstruction involving surface and subsurface atoms on Si(001). It
      leads to self-assembly of long nanowires of group-V elements (Bi, Sb) in the
      trenches of surface dimer vacancy lines (DVLs) with a characteristic double-dimer
      configuration. The key to this is the lowering of the kinetic barrier by the DATA
      process in conjunction with a favorable interaction between ad-dimers and step
      edges in DVLs. The present results provide an excellent account for experimental
      observations and reveal the atomistic origin and the dynamic transformation path
      for nanowire self-assembly on Si(001).

PMID- 16090414
TI  - Charging of metal atoms on ultrathin MgO/Mo(100) films.
AB  - The chemical activity of supported metal nanoclusters is enhanced by electronic
      charging induced by the interaction with surface defects. We use density
      functional theory plane wave calculations to show that charging of metal atoms
      with high electron affinity like Au is possible also in the absence of defects by
      atom deposition on ultrathin MgO films (1 to 3 layers) grown on Mo(100). The Au
      6s level falls below the Fermi level of Mo, leading to electron transfer from Mo
      to Au by direct tunneling through the insulating MgO film. The effect is not
      observed for Pd, whose 5s empty level falls just above the Fermi level of Mo, or
      for thicker MgO films.

PMID- 16090415
TI  - Long-distance diffusion of excitons in double quantum well structures.
AB  - In this Letter we report on lateral diffusion measurements of excitons at low
      temperature in double quantum wells of various widths. The structure is designed
      so that excitons live up to 30 micros and diffuse up to 500 microm. Particular
      attention is given to establishing that the transport occurs by exciton motion.
      The deduced exciton diffusion coefficients have a very strong well width
      dependence, and obey the same power law as the diffusion coefficient for
      electrons.

PMID- 16090416
TI  - Field-induced suppression of the heavy-fermion state in YbRh2Si2.
AB  - We report dc-magnetization measurements on YbRh2Si2 at temperatures down to 0.04
      K, magnetic fields B< or =11.5 T, and under hydrostatic pressure P< or =1.3 GPa.
      At ambient pressure a kink at B* =9.9 T indicates a new type of field-induced
      transition from an itinerant to a localized 4f state. This transition is
      different from the metamagnetic transition observed in other heavy-fermion
      compounds, as here ferromagnetic rather than antiferromagnetic correlations
      dominate below B*. Hydrostatic pressure experiments reveal a clear correspondence
      of B* to the characteristic spin fluctuation temperature determined from specific
      heat.

PMID- 16090417
TI  - STS observations of Landau levels at graphite surfaces.
AB  - Scanning tunneling spectroscopy (STS) measurements were made on surfaces of two
      different kinds of graphite samples, Kish graphite and highly oriented pyrolytic
      graphite (HOPG), at very low temperatures and in high magnetic fields. We
      observed a series of peaks in the tunnel spectra associated with Landau
      quantization of the quasi-two-dimensional electrons and holes. A comparison with
      the calculated local density of states at the surface layers allows us to
      identify Kish graphite as bulk graphite and HOPG as graphite with a finite
      thickness of 40 layers. This explains the qualitative difference between the two
      graphites reported in the recent transport measurements which suggested the
      quantum-Hall effect in HOPG. This work demonstrates how powerful the combined
      approach between the high quality STS measurement and the first-principles
      calculation is in material science.

PMID- 16090418
TI  - Spin-orbit coupling and anisotropy of spin splitting in quantum dots.
AB  - In lateral quantum dots, the combined effect of both Dresselhaus and Bychkov
      Rashba spin-orbit coupling is equivalent to an effective magnetic field +/- B(SO)
      which has the opposite sign for s(z)= +/- 1/2 spin electrons. When the external
      magnetic field is perpendicular to the planar structure, the field B(SO)
      generates an additional splitting for electron states as compared to the spin
      splitting in the in-plane field orientation. The anisotropy of spin splitting has
      been measured and then analyzed in terms of spin-orbit coupling in several
      AlGaAs/GaAs quantum dots by means of resonant tunneling spectroscopy. From the
      measured values and sign of the anisotropy we are able to determine the
      dominating spin-orbit coupling mechanism.

PMID- 16090419
TI  - Effects of thickness on the spin susceptibility of the two dimensional electron
      gas.
AB  - Using available quantum Monte Carlo predictions for a strictly 2D electron gas,
      we estimate the spin susceptibility of electrons in actual devices taking into
      account the effect of the finite transverse thickness and finding very good
      agreement with experiments. A weak disorder, as found in very clean devices
      and/or at densities not too low, just brings about a minor enhancement of the
      susceptibility.

PMID- 16090420
TI  - Bragg diffraction of microcavity polaritons by a surface acoustic wave.
AB  - Bragg scattering of polaritons by a coherent acoustic wave is mediated and
      strongly enhanced by the exciton states resonant with the acoustic and optic
      fields in the intraband and interband transitions, respectively. In this case, in
      contrast with conventional acousto-optics, the resonantly enhanced Bragg spectra
      reveal the multiple orders of diffracted light. For polaritons in GaAs
      microcavities driven by a surface acoustic wave of nu(SAW)=1 GHz and I(ac)< or
      approximately 100 W/cm(2) the main acoustically induced band gap can be as large
      as Delta(MC)(ac) approximately equal to 0.6 meV and the Bragg replicas up to n=3
      can be observed.

PMID- 16090421
TI  - Ab initio calculation of the intrinsic spin Hall effect in semiconductors.
AB  - Relativistic band theoretical calculations reveal that intrinsic spin Hall
      conductivity in hole-doped archetypical semiconductors Ge, GaAs, and AlAs is
      large [approximately 100(planck/e)(Omega cm)(-1)], showing the possibility of a
      spin Hall effect beyond the four-band Luttinger Hamiltonian. The calculated
      orbital-angular-momentum (orbital) Hall conductivity is one order of magnitude
      smaller, indicating no cancellation between the spin and orbital Hall effects in
      bulk semiconductors. Furthermore, it is found that the spin Hall effect can be
      strongly manipulated by strains, and that the ac spin Hall conductivity is large
      in pure as well as doped semiconductors.

PMID- 16090422
TI  - Pressure-induced non-Fermi-liquid behavior of PrNiO3.
AB  - Comprehensive temperature scans of the resistivity of a high-quality sample of
      PrNiO3 were made under different pressures up to 30 kbar; they have revealed that
      the insulator phase is suppressed completely at P approximately equal to 13 kbar,
      transforming to a non-Fermi-liquid phase in which the resistivity varies as
      Deltarho=rho(T)-rho(0) approximately T(n) with n=1.33 and 1.60 over a broad
      pressure range.

PMID- 16090423
TI  - Current-driven oscillations and time-dependent transport in nanojunctions.
AB  - Resonance inelastic conduction in molecular-scale electronics can be used to
      channel energy into a given mode of the molecular component to generate a desired
      motion. Dependence of the conductance properties on the molecular configuration,
      in turn, leads to a time-modulated current whose temporal properties are subject
      to control. We use an ab initio nonequilibrium formalism and the example of Au
      C60-Au junctions to illustrate the strongly correlated phenomena of current
      driven dynamics and time-dependent conductance in nanoelectronics, noting
      implications to, and potential applications in, several disciplines.

PMID- 16090424
TI  - Magnetic-field-induced insulating phases at large r s.
AB  - Exploring a two-dimensional hole system in the large r(s) regime we found a
      surprisingly rich phase diagram. At the highest densities, beside the nu =1/3,
      2/3, and 2/5 fractional quantum Hall states, we observe both of the previously
      reported high field insulating and reentrant insulating phases. As the density is
      lowered, the reentrant insulating phase initially strengthens, then it
      unexpectedly starts weakening until it completely disappears. The intricate
      behavior of the insulating phases can be explained by a nonmonotonic melting line
      in the nu-r(s) phase space.

PMID- 16090425
TI  - Spin-orbit-driven coherent oscillations in a few-electron quantum dot.
AB  - We propose an experiment to observe coherent oscillations in a single quantum dot
      with the oscillations driven by spin-orbit interaction. This is achieved without
      spin-polarized leads, and relies on changing the strength of the spin-orbit
      coupling via an applied gate pulse. We derive an effective model of this system
      which is formally equivalent to the Jaynes-Cummings model of quantum optics. For
      parameters relevant to an InGaAs dot, we calculate a Rabi frequency of 2 GHz.

PMID- 16090426
TI  - Vortex-antivortex nucleation in magnetically nanotextured superconductors:
      magnetic-field-driven and thermal scenarios.
AB  - Within the Ginzburg-Landau formalism, we predict two novel mechanisms of vortex
      antivortex nucleation in a magnetically nanostructured superconductor. Although
      counterintuitive, nucleation of vortex-antivortex pairs can be activated in a
      superconducting (SC) film covered by arrays of submicron ferromagnets (FMs) when
      exposed to an external homogeneous magnetic field. In another scenario, we
      predict the thermal induction of vortex-antivortex configurations in SC-FM
      samples. This phenomenon leads to a new type of Little-Parks oscillations of the
      FM magnetization-temperature phase boundary of the SC film.

PMID- 16090427
TI  - Ground-state entanglement of the BCS model.
AB  - The concept of local concurrence is used to quantify the entanglement between a
      single qubit and the remainder of a multiqubit system. For the ground state of
      the BCS model in the thermodynamic limit the set of local concurrences completely
      describes the entanglement. As a measure for the entanglement of the full system
      we investigate the average local concurrence (ALC). We find that the ALC
      satisfies a simple relation with the order parameter. We then show that for
      finite systems with a fixed particle number, a relation between the ALC and the
      condensation energy exposes a threshold coupling. Below the threshold,
      entanglement measures besides the ALC are significant.

PMID- 16090428
TI  - Nickel impurity-induced enhancement of the pseudogap of cuprate high-T(c)
      superconductors.
AB  - The influence of magnetic Ni and nonmagnetic Zn impurities on the normal-state
      pseudogap (PG) in the c-axis optical conductivity of (Sm,Nd)Ba(2){Cu(1
      y)(Ni,Zn)(y)}(3)O(7-delta) crystals was studied by spectral ellipsometry. We find
      that these impurities, which strongly suppress superconductivity, have a
      profoundly different impact on the PG. Zn gives rise to a gradual and
      inhomogeneous PG suppression while Ni strongly enhances the PG. Our results
      challenge theories that relate the PG either to precursor superconductivity or to
      other phases with exotic order parameters, such as flux phase or d-density wave
      states, that should be suppressed by potential scattering. The apparent
      difference between magnetic and nonmagnetic impurities instead points towards an
      important role of magnetic correlations in the PG state.

PMID- 16090429
TI  - 17O NMR studies of a triangular-lattice superconductor NaxCoO2 x yH(2)O.
AB  - We report the first 17O NMR studies of a triangular-lattice superconductor
      Na(1/3)CoO2 x 4/3H(2)O and the host material Na(x)CoO2 (x=0.35 and 0.72). Knight
      shift measurements reveal that p-d hybridization induces sizable spin
      polarization in the O triangular-lattice layers. Water intercalation makes CoO2
      planes homogeneous and enhances low frequency spin fluctuations near T(c)=4.5 K
      at some finite wave vectors different from both the ferromagnetic and "120
      degree" modes.

PMID- 16090430
TI  - Observation of interband pairing interaction in a two-band superconductor: MgB2.
AB  - The recently discovered anisotropic superconductor MgB2 is the first of its kind
      showing the intriguing properties of two-band superconductivity. By tunneling
      experiments using thin film tunnel junctions, electron-coupled phonon spectra
      were determined showing that superconductivity in MgB2 is phonon mediated. In a
      further analysis, which involves first principles calculations, the strongest
      feature in these spectra could be traced back to the key quantity of two-band
      superconductivity, the interband pairing interaction. For the phonons, this
      interaction turns out quite selective. It involves mainly low-energy optical
      phonon modes, where the boron atoms move perpendicular to the boron planes.

PMID- 16090431
TI  - Experimental observation of the 1/3 magnetization plateau in the diamond-chain
      compound Cu3(CO3)2(OH)2.
AB  - The magnetic susceptibility, high field magnetization, and specific heat
      measurements of Cu3(CO3)2(OH)2, which is a model substance for the frustrating
      diamond spin chain model, have been performed using single crystals. Two broad
      peaks are observed at around 20 and 5 K in both magnetic susceptibility and
      specific heat results. The magnetization curve has a clear plateau at one third
      of the saturation magnetization. The experimental results are examined in terms
      of theoretical expectations based on exact diagonalization and density matrix
      renormalization group methods. An origin of magnetic anisotropy is also
      discussed.

PMID- 16090432
TI  - Reentrant spin-glass transition in a dilute magnet.
AB  - We perform a large-scale Monte Carlo simulation of a dilute classical Heisenberg
      model with ferromagnetic nearest neighbor and antiferromagnetic next-nearest
      neighbor interactions. We found that the model reproduces a reentrant spin-glass
      transition. That is, as the temperature is decreased, the magnetization increases
      rapidly below a certain temperature, reaches a maximum value, and then disappears
      at some lower temperature. The low temperature phase was suggested to be a spin
      glass phase that is characterized by ferromagnetic clusters.

PMID- 16090433
TI  - Observation of giant magnetic linear dichroism in (Ga, Mn) As.
AB  - Giant magnetic linear dichroism (MLD) is observed in the ferromagnetic
      semiconductor Ga(0.98)Mn(0.02)As. The contribution to this effect induced by the
      spontaneous magnetization can be clearly identified by azimuthal dependencies.
      The spectral dependence of the effect in the range from 1.4 to 2.4 eV shows that
      the MLD induced by the spontaneous magnetization is strongly enhanced for
      excitations from the electronic states that are responsible for the
      ferromagnetism in this material. This spectral sensitivity and the size of the
      effect makes MLD a powerful tool for the study of (III, Mn)V alloys and similar
      novel ferromagnetic semiconductors.

PMID- 16090434
TI  - Magnetization process in holmium: easy axis spin reorientation induced by the
      magnetostrictive basal plane distortion.
AB  - We report on the change of the easy axis direction in holmium, from the a to the
      b axis, under the application of a magnetic field in the basal plane. This spin
      reorientation is observed by measuring the magnetic torque in Ho(n)/Lu(15)
      superlattices (n and 15 are the number of atomic planes in the Ho and Lu blocks).
      We also observe that, at the field H0 and temperature at which the reorientation
      occurs, both axes are easy directions. Based on the fact that the field H0
      depends on n in the same way as the field-induced magnetoelastic distortion does,
      we propose that this spin reorientation originates from the strong field-induced
      magnetoelastic deformation within the basal plane. The modulation of the alpha
      strains with sixfold symmetry originates a 12-fold term in the magnetic
      anisotropy energy.

PMID- 16090435
TI  - Evidence for noncollinearity between surface and bulk magnetization in ultrathin
      Co films.
AB  - The magnetization reversal of ultrathin Co films on Cu(001) has been investigated
      by grazing ion scattering and magneto-optical Kerr effect. Differences in the
      behavior of surface and bulk magnetization are found and attributed to the
      reduced coordination and site symmetry at the surface. The reversal behavior of
      the surface magnetization depends on the chemical surface composition. For pure
      Co films, the reversal of the bulk magnetization is preceded by a complete
      reversal of the surface magnetization. A particular magnetic state of the surface
      is suggested as a precursor for magnetization reversal.

PMID- 16090436
TI  - Ultrafast core-hole-induced dynamics in water probed by x-ray emission
      spectroscopy.
AB  - The isotope effect and excitation-energy dependence have been measured in the
      oxygen K-edge x-ray emission spectrum (XES). The use of XES to monitor core decay
      processes provides information about molecular dynamics (MD) on an ultrafast time
      scale through the O1s lifetime of a few femtoseconds. Different nuclear masses
      give rise to differences in the dynamics and the observed isotope effect in XES
      is direct evidence of the importance of such processes. MD simulations show that
      even the excitation-energy dependence in the XES is mainly related to differences
      in core-excited-state dynamics.

PMID- 16090437
TI  - Modified spontaneous emission and qubit entanglement from dipole-coupled quantum
      dots in a photonic crystal nanocavity.
AB  - The modified spontaneous emission dynamics of two photon-coupled quantum dots in
      a planar-photonic crystal are theoretically investigated. Based on a photon Green
      function technique for quantizing the electromagnetic fields in arbitrary
      surroundings, pronounced vacuum Rabi oscillations and dipole-dipole interactions
      are self-consistently incorporated and are shown to result in a high degree of
      quantum-bit entanglement. Quantum dots with different optical dipole moments are
      also found to yield a very rich display of quantum dynamics and offer several
      advantages over coupling identical atoms.

PMID- 16090438
TI  - Stimulated and spontaneous optical generation of electron spin coherence in
      charged GaAs quantum dots.
AB  - We report on the coherent optical excitation of electron spin polarization in the
      ground state of charged GaAs quantum dots via an intermediate charged exciton
      (trion) state. Coherent optical fields are used for the creation and detection of
      the Raman spin coherence between the spin ground states of the charged quantum
      dot. The measured spin decoherence time, which is likely limited by the nature of
      the spin ensemble, approaches 10 ns at zero field. We also show that the Raman
      spin coherence in the quantum beats is caused not only by the usual stimulated
      Raman interaction but also by simultaneous spontaneous radiative decay of either
      excited trion state to a coherent combination of the two spin states.

PMID- 16090439
TI  - Modeling surfactant adsorption on hydrophobic surfaces.
AB  - Surfactant adsorption on hydrophobic surfaces is of current interest in attempts
      to solubilize single-wall carbon nanotubes and to render quantum dots
      biocompatible. A coarse grained method is presented for incorporating a
      hydrophobic surface into existing liquid force fields by appealing to statistical
      mechanics and probability theory. The dimensionality problem which arises is
      overcome with an approximate treatment and the entire procedure is applied to
      aqueous n-alkyl poly(ethylene oxide) adsorbing onto a graphite surface. The
      simulations are in excellent agreement with atomic force microscopy data. The
      mechanism of micelle adsorption onto a partially coated surface is reported for
      the first time and has implications for the construction of nanotemplates.

PMID- 16090440
TI  - Convex error growth patterns in a global weather model.
AB  - We investigate the error growth, that is, the growth in the distance E between
      two typical solutions of a weather model. Typically E grows until it reaches a
      saturation value E(s). We find two distinct broad log-linear regimes, one for E
      below 2% of E(s) and the other for E above. In each, log (E/E(s)) grows as if
      satisfying a linear differential equation. When plotting d log(E)/dt vs log(E),
      the graph is convex. We argue this behavior is quite different from other
      dynamics problems with saturation values, which yield concave graphs.

PMID- 16090441
TI  - Comment on "Fano line shapes reconsidered: symmetric photoionization peaks from
      pure continuum excitation".

PMID- 16090443
TI  - Comment on "Josephson current through a nanoscale magnetic quantum dot".

PMID- 16090445
TI  - An intrinsic limit to quantum coherence due to spontaneous symmetry breaking.
AB  - We investigate the influence of spontaneous symmetry breaking on the decoherence
      of a many-particle quantum system. This decoherence process is analyzed in an
      exactly solvable model system that is known to be representative of symmetry
      broken macroscopic systems in equilibrium. It is shown that spontaneous symmetry
      breaking imposes a fundamental limit to the time that a system can stay quantum
      coherent. This universal time scale is t(spon) approximately = 2piNH/(kBT), given
      in terms of the number of microscopic degrees of freedom N, temperature T, and
      the constants of Planck (h) and Boltzmann (kB).

PMID- 16090446
TI  - Dynamics of narrow bright solitons in an array of attractive atoms in a Bose
      Einstein condensate.
AB  - We study the dynamics of a narrow bright soliton in a one-dimensional lattice of
      condensed attractive atoms when the soliton width is comparable to the lattice
      spacing. If a momentum is imprinted to a stationary state, the soliton can have
      oscillations around a site or it can undergo a random motion along the array. The
      motion is very sensitive to the atomic background distribution, and a thermal
      cloud or quantum field fluctuations can induce a random motion of the soliton.

PMID- 16090447
TI  - Quantum phase transitions across a p-wave Feshbach resonance.
AB  - We study a single-species polarized Fermi gas tuned across a narrow p-wave
      Feshbach resonance. We show that in the course of a Bose-Einstein condensation
      (BEC)-BCS crossover, the system can undergo a magnetic-field-tuned quantum phase
      transition from a px-wave to a px+ipy-wave superfluid. The latter state, that
      spontaneously breaks time-reversal symmetry, furthermore undergoes a topological
      px+ipy to px+ipy transition at zero chemical potential mu. In two dimensions, for
      mu > 0 it is characterized by a Pfaffian ground state exhibiting topological
      order and non-Abelian excitations familiar from fractional quantum Hall systems.

PMID- 16090448
TI  - Quantum phases in a resonantly interacting boson-fermion mixture.
AB  - We consider a resonantly interacting boson-fermion mixture of 40K and 87Rb atoms
      in an optical lattice. We show that by using a red-detuned optical lattice the
      mixture can be accurately described by a generalized Hubbard model for 40K and
      87Rb atoms, and 40K-87Rb molecules. The microscopic parameters of this model are
      fully determined by the details of the optical lattice and the interspecies
      Feshbach resonance in the absence of the lattice. We predict a quantum phase
      transition to occur in this system already at low atomic filling fraction, and
      present the phase diagram as a function of the temperature and the applied
      magnetic field.

PMID- 16090449
TI  - Experimental error filtration for quantum communication over highly noisy
      channels.
AB  - Error filtration is a method for encoding the quantum state of a single particle
      into a higher dimensional Hilbert space in such a way that it becomes less
      sensitive to noise. We have realized a fiber optics demonstration of this method
      and illustrated its potentialities by carrying out the optical part of a quantum
      key distribution scheme over a line whose phase noise is too high for a standard
      implementation of BB84 to be secure. By filtering out the noise, a bit error rate
      of 15.3% +/- 0.1%, which is beyond the security limit, can be reduced to 10.6% +/
      0.1%, thereby guaranteeing the cryptographic security.

PMID- 16090450
TI  - Asymptotically optimal quantum circuits for d-level systems.
AB  - Scalability of a quantum computation requires that the information be processed
      on multiple subsystems. However, it is unclear how the complexity of a quantum
      algorithm, quantified by the number of entangling gates, depends on the subsystem
      size. We examine the quantum circuit complexity for exactly universal computation
      on many d-level systems (qudits). Both a lower bound and a constructive upper
      bound on the number of two-qudit gates result, proving a sharp asymptotic of
      theta(d(2n)) gates. This closes the complexity question for all d-level systems
      (d finite). The optimal asymptotic applies to systems with locality constraints,
      e.g., nearest neighbor interactions.

PMID- 16090451
TI  - Beating the photon-number-splitting attack in practical quantum cryptography.
AB  - We propose an efficient method to verify the upper bound of the fraction of
      counts caused by multiphoton pulses in practical quantum key distribution using
      weak coherent light, given whatever type of Eve's action. The protocol simply
      uses two coherent states for the signal pulses and vacuum for the decoy pulse.
      Our verified upper bound is sufficiently tight for quantum key distribution with
      a very lossy channel, in both the asymptotic and nonasymptotic case. So far our
      protocol is the only decoy-state protocol that works efficiently for currently
      existing setups.

PMID- 16090452
TI  - Decoy state quantum key distribution.
AB  - There has been much interest in quantum key distribution. Experimentally, quantum
      key distribution over 150 km of commercial Telecom fibers has been successfully
      performed. The crucial issue in quantum key distribution is its security.
      Unfortunately, all recent experiments are, in principle, insecure due to real
      life imperfections. Here, we propose a method that can for the first time make
      most of those experiments secure by using essentially the same hardware. Our
      method is to use decoy states to detect eavesdropping attacks. As a consequence,
      we have the best of both worlds--enjoying unconditional security guaranteed by
      the fundamental laws of physics and yet dramatically surpassing even some of the
      best experimental performances reported in the literature.

PMID- 16090453
TI  - Langevin description of critical phenomena with two symmetric absorbing states.
AB  - On the basis of general considerations, we propose a Langevin equation accounting
      for critical phenomena occurring in the presence of two symmetric absorbing
      states. We study its phase diagram by mean-field arguments and direct numerical
      integration in physical dimensions. Our findings fully account for and clarify
      the intricate picture known so far from the aggregation of partial results
      obtained with microscopic models. We argue that the direct transition from
      disorder to one of two absorbing states is best described as a (generalized)
      voter critical point and show that it can be split into an Ising and a directed
      percolation transition in dimensions larger than one.

PMID- 16090454
TI  - Sub-Hertz optical frequency comparisons between two trapped 171Yb+ ions.
AB  - We compare the frequencies of the 6s2S(1/2)(F = 0)-->5d2D(3/2)(F = 2) reference
      transition in 171Yb+ for two single ions stored in independent traps. The
      quadrupole moment of the 5d2D(3/2) state is measured to be 9.32(48) x 10(-40) C
      m2 and from the quadratic Stark shift the relevant scalar and tensor
      polarizabilities are determined to be alphaS(S(1/2)) - alphaS(D(3/2)) = -6.9(1.4)
      x 10(-40) J m2/V2 and alphaT(D(3/2)) = -13.6(2.2) x 10(-40) J m2/V2,
      respectively. In the absence of external perturbations we find a mean frequency
      difference between the two trapped ions of 0.26(42) Hz, corresponding to a
      relative difference of 3.8(6.1) x 10(-16). This is comparable to the agreement
      found in the most accurate comparisons between cesium fountain clocks.

PMID- 16090455
TI  - Constraining the spectrum of supernova neutrinos from nu-process induced light
      element synthesis.
AB  - We constrain energy spectra of supernova neutrinos through the avoidance of an
      overproduction of the 11B abundance during Galactic chemical evolution. In
      supernova nucleosynthesis calculations with a parametrized neutrino spectrum as a
      function of temperature of nu(mu,tau) and nu(mu,tau) and total neutrino energy,
      we find a strong neutrino temperature dependence of the 11B yield. When the yield
      is combined with observed abundances, the acceptable range of the nu(mu,tau) and
      nu(mu,tau) temperature is found to be 4.8 to 6.6 MeV. Nonzero neutrino chemical
      potentials would reduce this temperature range by about 10% for a degeneracy
      parameter eta(nu) = mu(nu)/kT(nu) smaller than 3.

PMID- 16090456
TI  - Transport of Mars-crossing asteroids from the quasi-Hilda region.
AB  - We employ set oriented methods in combination with graph partitioning algorithms
      to identify key dynamical regions in the Sun-Jupiter-particle three-body system.
      Transport rates from a region near the 3:2 Hilda resonance into the realm of
      orbits crossing Mars' orbit are computed. In contrast to common numerical
      approaches, our technique does not depend on single long term simulations of the
      underlying model. Thus, our statistical results are particularly reliable since
      they are not affected by a dynamical behavior which is almost nonergodic (i.e.,
      dominated by strongly almost invariant sets).

PMID- 16090458
TI  - High-density QCD and cosmic-ray air showers.
AB  - We discuss particle production in the high-energy, small-x limit of QCD where the
      gluon density of hadrons is expected to become nonperturbatively large. Strong
      modifications of the phase-space distribution of produced particles as compared
      to leading-twist models are predicted, which reflect in the properties of cosmic
      ray induced air showers in the atmosphere. Assuming hadronic primaries, our
      results suggest a light composition near Greisen-Zatsepin-Kuzmin cutoff energies.
      We also show that cosmic-ray data are sensitive to various QCD evolution
      scenarios for the rate of increase of the gluon density at small x, such as fixed
      coupling and running-coupling Balitsky-Fadin-Kuraev-Lipatov evolution. There are
      clear indications for a slower growth of the gluon density as compared to RHIC
      and HERA, due, e.g., to running-coupling effects.

PMID- 16090457
TI  - Measurement of the time-dependent CP-violating asymmetry in B(0)-
      >K(0)(S)pi(0)gamma decays.
AB  - We present a new measurement of CP-violation parameters in B(0)-
      >K(0)(S)pi(0)gamma decay based on a sample of 275 x 10(6) BB pairs collected at
      the Gamma(4S) resonance with the Belle detector at the KEKB energy-asymmetric
      e(+)e(-) collider. One of the B mesons is fully reconstructed in the B(0)-
      >K(0)(S)pi(0)gamma decay. The flavor of the accompanying B meson is identified
      from its decay products. CP-violation parameters are obtained from the asymmetry
      in the distribution of the proper time intervals between the two B decays. We
      obtain SK(0)(S)(pi(0)gamma) = -0.58(+0.46)(-0.38)(stat) +/- 0.11(syst) and
      AK(0)(S)(pi(0)gamma) = +0.03 +/- 0.34(stat) +/- 0.11(syst), for the K(0)(S)pi(0)
      invariant mass covering the full range up to 1.8 GeV/c2. We also measure the CP
      violation parameters for the case B(0)-->K(*0)(-->K(0)(S)pi(0))gamma and obtain
      S(K(*0)gamma) = -0.79(+0.63)(-0.50)(stat) +/- 0.10(syst) for A(K(*0)gamma) fixed
      at 0.

PMID- 16090459
TI  - Determining gamma from B --> pi(pi) decays without the CP-asymmetry Cpi(0)pi(0).
AB  - Factorization based on the soft-collinear effective theory (SCET) can be used to
      reduce the number of hadronic parameters in an isospin analysis of B --> pi(pi)
      decays by one. This gives a theoretically precise method for determining the CP
      violating phase gamma by fitting to the B --> pi(pi) data without Cpi(0)pi(0).
      SCET predicts that gamma lies close to the isospin bounds. With the current world
      averages we find gamma = 75 degrees +/- 2 degrees(+9 degrees)(-13 degrees), where
      the uncertainties are theoretical, then experimental.

PMID- 16090461
TI  - Branching fractions for psi(2S)-to-J/psi transitions.
AB  - We describe new measurements of the inclusive and exclusive branching fractions
      for psi(2S) transitions to J/psi using e(+)e(-) collision data collected with the
      CLEO detector operating at CESR. All branching fractions and ratios of branching
      fractions reported here represent either the most precise measurements to date or
      the first direct measurements. Indirectly and in combination with other CLEO
      measurements, we determine B(chi(cJ) --> gamma(J/psi)) and B[psi(2S) --> light
      hadrons].

PMID- 16090464
TI  - First observation of 54Zn and its decay by two-proton emission.
AB  - The nucleus 54Zn has been observed for the first time in an experiment at the
      SISSI/LISE3 facility of GANIL in the quasifragmentation of a 58Ni beam at 74.5
      MeV/nucleon in a (nat)Ni target. The fragments were analyzed by means of the
      ALPHA-LISE3 separator and implanted in a silicon-strip detector where
      correlations in space and time between implantation and subsequent decay events
      allowed us to generate almost background free decay spectra for about 25
      different nuclei at the same time. Eight 54Zn implantation events were observed.
      From the correlated decay events, the half-life of 54Zn is determined to be
      3.2(+1.8)(-0.8) ms. Seven of the eight implantations are followed by two-proton
      emission with a decay energy of 1.48(2) MeV. The decay energy and the partial
      half-life are compared to model predictions and allow for a test of these two
      proton decay models.

PMID- 16090465
TI  - Nuclear time-reversal violation and the Schiff moment of 225Ra.
AB  - We present a comprehensive mean-field calculation of the Schiff moment of the
      nucleus 225Ra, the quantity that determines the static electric-dipole moment of
      the corresponding atom if time-reversal (T) invariance is violated in the
      nucleus. The calculation breaks all possible intrinsic symmetries of the nuclear
      mean field and includes, in particular, both exchange and direct terms from the
      full finite-range T-violating nucleon-nucleon interaction, and the effects of
      short-range correlations. The resulting Schiff moment, which depends on three
      unknown T-violating pion-nucleon coupling constants, is much larger than in
      199Hg, the isotope with the best current experimental limit on its atomic
      electric-dipole moment.

PMID- 16090466
TI  - Formation of eta'(958)-mesic nuclei and axial UA(1) anomaly at finite density.
AB  - We discuss the possibility of producing the bound states of the eta'(958) meson
      in nuclei theoretically. We calculate the formation cross sections of the eta'
      bound states with the Green function method for the (gamma, p) reaction and
      discuss the experimental feasibility at photon facilities such as SPring-8. We
      conclude that we can expect to observe resonance peaks in (gamma, p) spectra for
      the formation of eta' bound states and we can deduce new information on eta'
      properties at finite density. These observations are believed to be essential to
      know the possible mass shift of eta' and deduce new information on the effective
      restoration of the chiral UA(1) anomaly in the nuclear medium.

PMID- 16090467
TI  - Response of polyatomic molecules to ultrastrong laser- and ion-induced fields.
AB  - The exposure of molecules to short, ultrastrong electric fields leads to multiple
      ionization and a subsequent Coulomb explosion. We present a comparative study
      where uracil molecules are exposed to fields generated by high-power laser pulses
      (tau approximately 75 fs, I > 10(16) W/cm2) or swift highly charged ions (0.5 MeV
      Xe25+) representing a half-cycle pulse of less than 10 fs duration. Molecular
      dynamics and structural information contained in the fragmentation pathways can
      be assessed separately. Despite the similar field strengths large differences in
      fragment kinetic energies are found which are related to field shape and duration
      with the aid of molecular dynamics simulations.

PMID- 16090462
TI  - Centrality dependence of direct photon production in (square root)S(NN) = 200 GeV
      Au + Au collisions.
AB  - The first measurement of direct photons in Au + Au collisions at (square
      root)S(NN) = 200 GeV is presented. The direct photon signal is extracted as a
      function of the Au + Au collision centrality and compared to next-to-leading
      order perturbative quantum chromodynamics calculations. The direct photon yield
      is shown to scale with the number of nucleon-nucleon collisions for all
      centralities.

PMID- 16090460
TI  - Measurement of inclusive differential cross sections for pp collisions at (square
      root)s = 1.96 TeV.
AB  - We present measurements of the inclusive production cross sections of the
      Gamma(1S) bottomonium state in pp collisions at (square root)s = 1.96 TeV. Using
      the Gamma(1S) --> mu(+)mu(-) decay mode for a data sample of 159 +/- 10 pb(-1)
      collected by the D0 detector at the Fermilab Tevatron collider, we determine the
      differential cross sections as a function of the Gamma(1S) transverse momentum
      for three ranges of the Gamma(1S) rapidity: 0 < y(Gamma) < or = 0.6, 0.6 <
      y(Gamma) < or = 1.2, and 1.2 < y(Gamma) < or = 1.8.

PMID- 16090468
TI  - Effective potential for natural spin orbitals.
AB  - For the first time the explicit form of the effective nonlocal potential for the
      natural spin orbitals is derived and analyzed. It is shown that in the case of
      the degenerate one-electron reduced density matrix the potential is not unique.
      The knowledge of the effective potential allows one to establish one-electron
      equations for the natural spin orbitals that may be of great value for efficient
      density matrix functional theory calculations.

PMID- 16090470
TI  - Electromagnetically induced magnetochiral anisotropy in a resonant medium.
AB  - Chirality has been extensively studied for well over a century, and its potential
      applications range from optics to chemistry, medicine, and biology. Ingenious
      experiments have been designed to measure this naturally small effect. Here we
      discuss the possibility of producing a medium having a large chiral effect by
      using the ideas of coherent control. The coherent fields resonant with
      appropriate transitions in atomic or molecular systems can be used to manipulate
      the optical properties of a medium. We demonstrate experimentally very large
      magnetochiral anisotropy by using electromagnetic fields in atomic Rb vapors.

PMID- 16090469
TI  - Anomalous size dependence in the melting temperatures of free sodium clusters: an
      explanation for the calorimetry experiments.
AB  - The meltinglike transition in unsupported Na(N) clusters (N = 55, 92, 147, 181,
      189, 215, 249, 271, 281 and 299) is studied by first-principles isokinetic
      molecular dynamics simulations. The irregular size dependence of the melting
      temperatures Tm observed in the calorimetry experiments of Schmidt et al. [Nature
      (London) 393, 238 (1998)] is quantitatively reproduced. We demonstrate that
      structural effects alone can explain all broad features of experimental
      observations. Specifically, maxima in Tm(N) correlate with high surface stability
      and with structural features such as a high compactness degree.

PMID- 16090463
TI  - Saturation of azimuthal anisotropy in Au + Au collisions at (square root)s(NN) =
      62-200 GeV.
AB  - New measurements are presented for charged hadron azimuthal correlations at
      midrapidity in Au+Au collisions at (square root)s(NN) = 62.4 and 200 GeV. They
      are compared to earlier measurements obtained at (square root)s(NN) = 130 GeV and
      in Pb + Pb collisions at (square root)s(NN) = 17.2 GeV. Sizeable anisotropies are
      observed with centrality and transverse momentum (pT) dependence characteristic
      of elliptic flow (upsilon2). For a broad range of centralities, the observed
      magnitudes and trends of the differential anisotropy, upsilon2(pT), change very
      little over the collision energy range (square root)s(NN) = 62-200 GeV,
      indicating saturation of the excitation function for upsilon2 at these energies.
      Such a saturation may be indicative of the dominance of a very soft equation of
      state for (square root)s(NN) approximately 60-200 GeV.

PMID- 16090471
TI  - Communication via the statistics of photon-number squeezed light.
AB  - A method of communication employing the second order statistics of photon-number
      squeezed light is demonstrated. The technique encodes the information content in
      both nonstationary noise processes and in the average optical power, thereby
      creating two orthogonal channels and increasing the transmission capacity.
      Communication via the fragile quantum state has potential applications for
      privatized communication.

PMID- 16090472
TI  - Wave chaos in real-world vertical-cavity surface-emitting lasers.
AB  - We report the onset of wave chaos in a real-world vertical-cavity surface
      emitting laser. In a joint experimental and modeling approach we demonstrate that
      a small deformation in one layer of the complicated laser structure changes the
      emission properties qualitatively. Based on the analysis of the spatial emission
      profiles and spectral eigenvalue spacing distributions, we attribute these
      changes to the transition from regular behavior to wave chaos, and justify the
      full analogy to two-dimensional billiards by model calculations. Hence, these
      lasers represent fascinating devices for wave chaos studies.

PMID- 16090473
TI  - Shadow effects in spiral phase contrast microscopy.
AB  - Recently it has been demonstrated that spatial filtering of images in microscopy
      with a spiral phase element in a Fourier plane of the optical path results in a
      strong edge enhancement of object structures. In principle the operation is
      isotropic, i.e., all phase edges of a sample object are highlighted
      simultaneously, independent of their local direction. However, here we
      demonstrate that the symmetry can be broken intentionally by controlling the
      phase of the central area of a spiral phase hologram, which is displayed at a
      computer controlled spatial light modulator. This produces an apparent shadow
      effect which can be rotated at video rate. The resulting relieflike impression of
      the sample topography with a longitudinal resolution in the subwavelength regime
      is demonstrated by imaging a standard low contrast test sample consisting of a
      human cheek cell.

PMID- 16090474
TI  - Velocity intermittency in a buoyancy subrange in a two-dimensional soap film
      convection experiment.
AB  - In a two-dimensional soap film convection experiment, the velocity fields are
      found to be strongly intermittent in the buoyancy subrange, which was reported to
      be nonintermittent in a recent numerical simulation. The structure functions
      Sq(l)(= <delta(upsilon)l(q)>) exhibit self-similar structures and can be
      described by power laws l(zetaq) for integers 8 > or = q < or = 1. By extending
      Kolmogorov's refined similarity hypothesis to our system, an analytical form is
      derived for the scaling exponent zeta(q) = q/2 + (mu/18)(3q - q2). Our
      measurements yield mu = 0.42, which is significantly greater than 0.2 found in
      high Reynolds number turbulence in wind tunnels.

PMID- 16090475
TI  - Nonlinear dynamics of a flow-focusing bubble generator: an inverted dripping
      faucet.
AB  - We describe the rich dynamic behavior--including period-doubling and period
      halving bifurcations, intermittency, and chaos--observed in the breakup of an
      inviscid fluid in a coflowing, viscous liquid, both confined in a microfabricated
      flow-focusing geometry. Experimental observations support inertia-dominated
      dynamics of the interface, and suggest the possible similarity to the dynamics of
      a topologically inverted counterpart of this system, that is, a dripping faucet.

PMID- 16090476
TI  - Compression of laser radiation in plasmas using electromagnetic cascading.
AB  - Compressing high-power laser beams in plasmas via generation of a coherent
      cascade of electromagnetic sidebands is described. The technique requires two
      copropagating beams detuned by a near-resonant frequency Omega approximately <
      omega(p). The ponderomotive force of the laser beat wave drives an electron
      plasma wave which modifies the refractive index of plasma so as to produce a
      periodic phase modulation of the laser field with the beat period tau(b) =
      2pi/Omega. A train of chirped laser beat notes (each of duration tau(b)) is thus
      created. The group velocity dispersion of radiation in plasma can then compress
      each beat note to a few-laser-cycle duration. As a result, a train of sharp
      electromagnetic spikes separated in time by tau(b) is formed. Depending on the
      plasma and laser parameters, chirping and compression can be implemented either
      concurrently in the same plasma or sequentially in different plasmas.

PMID- 16090477
TI  - Transition to collisionless ion-temperature-gradient-driven plasma turbulence: a
      dynamical systems approach.
AB  - The transition to collisionless ion-temperature-gradient-driven plasma turbulence
      is considered by applying dynamical systems theory to a model with 10 degrees of
      freedom. The study of a four-dimensional center manifold predicts a "Dimits
      shift" of the threshold for turbulence due to the excitation of zonal flows and
      establishes (for the model) the exact value of that shift.

PMID- 16090478
TI  - Stationary vortical flows in two-dimensional plasma and in planetary atmospheres.
AB  - We derive the equation governing the asymptotic stationary states generated by
      decaying turbulence in two-dimensional plasma and planetary atmosphere. These
      fluids may be described by the Charney-Hasegawa-Mima equation and their
      relaxation states show a high degree of organization in vortical flows, similar
      to the Euler fluid. We develop a field-theoretical framework and show that these
      systems attain at stationarity the extremum of an energy functional corresponding
      to self-dual fields.

PMID- 16090479
TI  - Classical rotational inertia of solid 4He.
AB  - The observation of reduced rotational inertia in a cell containing solid 4He has
      been interpreted as evidence for superfluidity of the solid. We propose an
      alternative explanation: slippage of the solid, due to grain boundary premelting
      between the solid and dense adsorbed layers at the container wall. We calculate
      the range of film thickness, and determine the viscosity that will account for
      the missing rotational inertia. Grain boundary premelting also explains inertial
      anomalies in an earlier study of solid helium in porous glass and indicates that
      the liquid is partially superfluid.

PMID- 16090480
TI  - Pressure control of conducting channels in single-wall carbon nanotube networks.
AB  - We measure electrical transport on networks of single-wall nanotube ropes as a
      function of temperature T, voltage V, and pressure up to 22 GPa. We observe
      Luttinger liquid (LL) behavior, a conductance proportional to T(alpha), and a
      dynamic conductance proportional to V(alpha). With pressure, conductance
      increases while alpha decreases, enabling us to test the theoretical prediction
      for LL behavior on the alpha dependence of the T and V independent coefficient of
      the tunneling conductance, and to obtain the high frequency cutoff of LL modes.
      The possible transition to a Fermi liquid at alpha-->0 is unattainable, as
      nanotubes collapse to an insulating state at high pressures.

PMID- 16090481
TI  - Melting curve of MgO from first-principles simulations.
AB  - First-principles calculations based on density functional theory, both with the
      local density approximation (LDA) and with generalized gradient corrections
      (GGA), have been used to simulate solid and liquid MgO in direct coexistence in
      the range of pressure 0 < or = p < or = 135 GPa. The calculated LDA zero pressure
      melting temperature is T(LDA)m = 3110 +/- 50 K, in good agreement with the
      experimental data. The GGA zero pressure melting temperature T(GGA)m = 2575 +/-
      100 K is significantly lower than the LDA one, but the difference between the GGA
      and the LDA is greatly reduced at high pressure. The LDA zero pressure melting
      slope is dT/dp approximately 100 K/GPa, which is more than 3 times higher than
      the currently available experimental one from Zerr and Boehler [Nature (London)
      371, 506 (1994)]. At the core mantle boundary pressure of 135 GPa MgO melts at Tm
      = 8140 +/- 150 K.

PMID- 16090482
TI  - Interacting classical dimers on the square lattice.
AB  - We study a model of close-packed dimers on the square lattice with a nearest
      neighbor interaction between parallel dimers. This model corresponds to the
      classical limit of quantum dimer models [D. S. Rokhsar and S. A. Kivelson, Phys.
      Rev. Lett. 61, 2376 (1988)]. By means of Monte Carlo and transfer matrix
      calculations, we show that this system undergoes a Kosterlitz-Thouless transition
      separating a low temperature ordered phase where dimers are aligned in columns
      from a high temperature critical phase with continuously varying exponents. This
      is understood by constructing the corresponding Coulomb gas, whose coupling
      constant is computed numerically. We also discuss doped models and implications
      on the finite-temperature phase diagram of quantum dimer models.

PMID- 16090483
TI  - Interplay between structure and size in a critical crystal nucleus.
AB  - We study the kinetics of crystal nucleation of an undercooled Lennard-Jones
      liquid using various path-sampling methods. We obtain the rate constant and
      elucidate the pathways for crystal nucleation. Analysis of the path ensemble
      reveals that crystal nucleation occurs along many different pathways, in which
      critical solid nuclei can be small, compact, and face centered cubic, but also
      large, less ordered, and more body centered cubic. The reaction coordinate thus
      includes, besides the cluster size, also the quality of the crystal structure.

PMID- 16090484
TI  - Dynamics of a bonding front.
AB  - A description of the bonding front propagation between two adhesive plates is
      proposed. The model relates the velocity of a bonding front to the adhesion
      energy, with application to wafer direct bonding. Its derivation is based on a
      competition between the bonding energy and the viscous drag of the air flow in
      the gap between the two wafers. The model describes well the experimental data,
      including the wafer deformation profile during bonding or the dependence of the
      velocity on the gas viscosity, pressure, and wafer thickness.

PMID- 16090485
TI  - Coulombic amino group-metal bonding: adsorption of adenine on Cu110.
AB  - The interaction between molecular amino groups and metal surfaces is analyzed
      from first-principles calculations using the adsorption of adenine on Cu110 as a
      model case. The amino group nitrogens are found to adsorb on top of the surface
      copper atoms. However, the bonding clearly cannot be explained in terms of
      covalent interactions. Instead, we find it to be largely determined by mutual
      polarization and Coulomb interaction between substrate and adsorbate.

PMID- 16090486
TI  - Time-resolved measurement of surface diffusion induced by femtosecond laser
      pulses.
AB  - Diffusion of atomic oxygen on a vicinal Pt111 surface induced by femtosecond
      laser pulses has been studied using optical second-harmonic generation as a
      sensitive in situ probe of the step coverage. Time-resolved studies of the
      hopping rate for step-terrace diffusion with a two-pulse correlation scheme
      reveal a time constant of 1.5 ps for the energy transfer from the electronic
      excitation of the substrate to the frustrated translations of the adsorbate.

PMID- 16090487
TI  - Surprises in the phase diagram of an anderson impurity model for a single C60(n-)
      molecule.
AB  - We find by Wilson numerical renormalization group and conformal field theory that
      a three-orbital Anderson impurity model for a C60(n-) molecule has a very rich
      phase diagram which includes non-Fermi-liquid stable and unstable fixed points
      with interesting properties, most notably high sensitivity to doping n. We
      discuss the implications of our results to the conductance behavior of C60-based
      single-molecule transistor devices.

PMID- 16090488
TI  - Shubnikov-de Haas oscillations and the magnetic-field-induced suppression of the
      charge ordered state in Na(0.5)CoO2.
AB  - We have performed electrical transport measurements at low temperatures and high
      magnetic fields in Na(0.5)CoO2 single crystals. Shubnikov-de Haas oscillations
      corresponding to only 1% of the area of the orthorhombic Brillouin zone were
      clearly observed, indicating that most of the original Fermi surface vanishes at
      the charge-ordering (CO) transition. In-plane magnetic fields were found to
      suppress strongly the CO state. For fields rotated within the conducting planes,
      we observe angular magnetoresistance oscillations whose periodicity changes from
      twofold to sixfold at the transition.

PMID- 16090489
TI  - Imaging spin flows in semiconductors subject to electric, magnetic, and strain
      fields.
AB  - Using scanning Kerr microscopy, we directly acquire two-dimensional images of
      spin-polarized electrons flowing laterally in bulk epilayers of n:GaAs. Optical
      injection provides a local dc source of polarized electrons, whose subsequent
      drift and/or diffusion is controlled with electric, magnetic, and--in particular-
      strain fields. Spin precession induced by controlled uniaxial stress along the
      <110> axes demonstrates the direct k-linear spin-orbit coupling of electron spin
      to the shear (off diagonal) components of the strain tensor, epsilon(xy).

PMID- 16090490
TI  - First principles study of work functions of single wall carbon nanotubes.
AB  - We perform first principles calculations on work functions of single wall carbon
      nanotubes, which can be divided into two classes according to tube diameter (D).
      For class I tubes (D > 1 nm), work functions lie within a narrow distribution
      (approximately 0.1 eV) and show no significant chirality or diameter dependence.
      For class II tubes (D < 1 nm), work functions show substantial changes, with
      armchair tubes decreasing monotonically with diameter, while zigzag tubes show
      the opposite trend. Surface dipoles and hybridization effects are shown to be
      responsible for the observed work function change.

PMID- 16090491
TI  - Two-channel Kondo effect in glasslike ThAsSe.
AB  - We present low-temperature heat and charge transport as well as caloric
      properties of a ThAsSe single crystal. An extra -AT(1/2) term in the electrical
      resistivity, independent of magnetic fields as high as 14 T, provides evidence
      for an unusual scattering of conduction electrons. Additionally, both the thermal
      conductivity and the specific heat show a glass-type temperature dependence which
      signifies the presence of tunneling states. These observations apparently point
      to an experimental realization of a two-channel Kondo effect derived from
      structural two-level systems.

PMID- 16090492
TI  - Size-dependent spintronic properties of dilute magnetic semiconductor
      nanocrystals.
AB  - The electronic structure and magnetic properties of Mn-doped Ge, GaAs, and ZnSe
      nanocrystals are investigated using real space ab initio pseudopotentials
      constructed within the local spin-density approximation. The ferromagnetic and
      half-metallicity trends found in the bulk are preserved in the nanocrystals.
      However, the Mn-related impurity states become much deeper in energy with
      decreasing nanocrystalline size, causing the ferromagnetic stabilization to be
      dominated by double exchange via localized holes rather than by a Zener-like
      mechanism.

PMID- 16090493
TI  - Atomic-scale imaging of wall-by-wall breakdown and concurrent transport
      measurements in multiwall carbon nanotubes.
AB  - We report the atomic-scale imaging with concurrent transport measurements of the
      breakdown of individual multiwall carbon nanotubes inside a transmission electron
      microscope equipped with a piezomanipulator. We found unexpectedly three distinct
      breakdown sequences: namely, from the outermost wall inward, from the innermost
      wall outward, and alternatively between the innermost and the outmost walls.
      Remarkably, a significant amount of current drop was observed when an innermost
      wall is broken, proving unambiguously that every wall is conducting. Moreover,
      the breakdown of each wall in any sequence initiates in the middle of the
      nanotube, not at the contact, proving that the transport is not ballistic.

PMID- 16090494
TI  - Solid-state circuit for spin entanglement generation and purification.
AB  - We show how realistic charge manipulation and measurement techniques, combined
      with the exchange interaction, allow for the robust generation and purification
      of four-particle spin entangled states in electrically controlled semiconductor
      quantum dots. The generated states are immunized to the dominant sources of noise
      via a dynamical decoherence-free subspace; all additional errors are corrected by
      a purification protocol. This approach may find application in quantum
      computation, communication, and metrology.

PMID- 16090495
TI  - Microscopic dielectric response functions in semiconductor quantum dots.
AB  - We calculate and model the microscopic dielectric response function for quantum
      dots using first principle methods. We find that the response is bulklike inside
      the quantum dots, and the reduction of the macroscopic dielectric constants is a
      surface effect. We present a model for the microscopic dielectric function which
      reproduces well the directly calculated results and can be used to solve the
      Poisson equation in a nanosystem.

PMID- 16090496
TI  - Effective theory of high-temperature superconductors.
AB  - The field theory of a fluctuating d-wave superconductor is constructed and
      proposed as an effective description of superconducting cuprates at low energies.
      The theory is used to resolve a puzzle posed by recent experiments on superfluid
      density in severely underdoped YBa2(Cu3)O(6+x). In particular, the overall
      temperature dependence of the superfluid density at low dopings is argued to be
      described well by the strongly anisotropic weakly interacting Bose gas, and thus
      approximately linear in temperature with an almost doping-independent slope.

PMID- 16090497
TI  - Isotope effect in the superfluid density of high-temperature superconducting
      cuprates: stripes, pseudogap, and impurities.
AB  - Underdoped cuprates exhibit a normal-state pseudogap, and their spins and doped
      carriers tend to spatially separate into 1D or 2D stripes. Some view these as
      central to superconductivity and others as peripheral and merely competing. Using
      La(2-x)Sr(x)Cu(1-y)Zn(y)O4 we show that an oxygen isotope effect in Tc and in the
      superfluid density can be used to distinguish between the roles of stripes and
      pseudogap and also to detect the presence of impurity scattering. We conclude
      that stripes and pseudogap are distinct, and both compete and coexist with
      superconductivity.

PMID- 16090498
TI  - Strain induced half-metal to semiconductor transition in GdN.
AB  - We investigate the electronic structure and magnetic properties of GdN as a
      function of unit cell volume. Based on the first-principles calculations of GdN,
      we observe that there is a transformation in the conduction properties associated
      with the volume increase: first from half-metallic to semimetallic, then
      ultimately to semiconducting. We show that applying stress can alter the carrier
      concentration as well as mobility of the holes and electrons in the majority spin
      channel. In addition, we found that the exchange parameters depend strongly on
      lattice constant, thus the Curie temperature of this system can be enhanced by
      applying stress or doping impurities.

PMID- 16090499
TI  - Quest for frustration driven distortion in Y2(Mo2)O(7).
AB  - We investigated the nature of the freezing in the geometrically frustrated
      Heisenberg spin glass Y2(Mo2)O(7) by measuring the temperature dependence of the
      static internal magnetic field distribution above the spin-glass temperature, Tg,
      using the muon spin relaxation technique. The evolution of the field distribution
      cannot be explained by changes in the spin susceptibility alone and suggests a
      lattice deformation. This possibility is addressed by numerical simulations of
      the Heisenberg Hamiltonian with magnetoelastic coupling at T > 0.

PMID- 16090500
TI  - Vanishing of the Breit-Wigner-Fano component in individual single-wall carbon
      nanotubes.
AB  - In order to decide definitely on the dependence of the intensity of the Breit
      Wigner-Fano (BWF) component with the size of the bundle, we have measured the
      radial breathing modes and tangential modes (TMs) of well defined metallic
      individual single-wall carbon nanotubes (SWCNTs) and individual SWCNT bundles. In
      this aim, a complete procedure including the preparation of the substrates, the
      sample preparation, atomic-force-microscopy imaging and Raman spectroscopy has
      been developed. From this procedure, we show unambiguously that the BWF component
      vanishes in isolated metallic SWCNTs. In other words, the observation of a BWF
      component in the TM bunch is an intrinsic feature of the metallic SWCNT bundle.

PMID- 16090501
TI  - Vibronic and magnetic excitations in the spin-orbital liquid state of FeSc2S4.
AB  - Inelastic neutron scattering results on the spin-orbital liquid in FeSc2S4 are
      presented. This sulfospinel reveals strong geometric frustration in the spin and
      in the orbital sector. In the present experiments the orbital liquid is evidenced
      by a clear spectroscopic signature of a dynamic Jahn-Teller effect with a
      vibronic splitting 3Gamma approximately 2 meV in agreement with theoretical
      estimates. The excitations of the spin liquid reveal strong dispersion and can be
      characterized as cooperative spin excitations in a supercooled paramagnet with a
      spin gap of Delta approximately 0.2 meV.

PMID- 16090502
TI  - Real space trajectory of the ultrafast magnetization dynamics in ferromagnetic
      metals.
AB  - We have measured the real space trajectory of the ultrafast magnetization
      dynamics in ferromagnetic metals induced by femtosecond optical pulses. Our
      approach allows the observation of the initial change of the modulus and
      orientation of the magnetization, occurring within a few hundreds of
      femtoseconds, as well as its subsequent precession and damping around the
      effective field. The role of the magnetocrystalline anisotropy shows up in the
      magnetization reorientation occurring during the electron-lattice relaxation. In
      addition, we propose a model which takes into account the initial demagnetization
      in the Bloch formalism describing the magnetization dynamics.

PMID- 16090503
TI  - Molecular visualization of conformation-triggered flow instability.
AB  - A new type of flow fingering instability was observed in monolayer-thick polymer
      films as they spread on a solid substrate. Tracing the movement of individual
      molecules by atomic force microscopy enabled us to follow the development of the
      flow instability on the molecular level and to understand the underlying physical
      mechanism. The fingering instability was observed to be triggered by
      conformational changes of brushlike macromolecules in response to the pressure
      gradient driving the flow.

PMID- 16090504
TI  - Coupling of two motor proteins: a new motor can move faster.
AB  - We study the effect of a coupling between two motor domains in highly processive
      motor protein complexes. A simple stochastic discrete model, in which the two
      parts of the protein molecule interact through some energy potential, is
      presented. The exact analytical solutions for the dynamic properties of the
      combined motor species, such as the velocity and dispersion, are derived in terms
      of the properties of free individual motor domains and the interaction potential.
      It is shown that the coupling between the motor domains can create a more
      efficient motor protein that can move faster than individual particles. The
      results are applied to analyze the motion of RecBCD helicase molecules.

PMID- 16090505
TI  - Elastic correlations in nucleosomal DNA structure.
AB  - The structure of DNA in the nucleosome core particle is studied using an elastic
      model that incorporates anisotropy in the bending energetics and twist-bend
      coupling. Using the experimentally determined structure of nucleosomal DNA [T. J.
      Richmond and C. A. Davey, Nature (London) 423, 145 (2003)], it is shown that
      elastic correlations exist between twist, roll, tilt, and stretching of DNA, as
      well as the distance between phosphate groups. The twist-bend coupling term is
      shown to be able to capture these correlations to a large extent, and a fit to
      the experimental data yields a new estimate of G = 25 nm for the value of the
      twist-bend coupling constant.

PMID- 16090506
TI  - Role of delays in shaping spatiotemporal dynamics of neuronal activity in large
      networks.
AB  - We study the effect of delays on the dynamics of large networks of neurons. We
      show that delays give rise to a wealth of bifurcations and to a rich phase
      diagram, which includes oscillatory bumps, traveling waves, lurching waves,
      standing waves arising via a period-doubling bifurcation, aperiodic regimes, and
      regimes of multistability. We study the existence and the stability of the
      various dynamical patterns analytically and numerically in a simplified rate
      model as a function of the interaction parameters. The results derived in that
      framework allow us to understand the origin of the diversity of dynamical states
      observed in large networks of spiking neurons.

PMID- 16090508
TI  - Synthesizing primary molecular relaxation processes in excitable gases using a
      two-frequency reconstructive algorithm.
AB  - Identifying molecular relaxation processes in excitable gases remains
      challenging. An algorithm that reconstructs the primary relaxation processes is
      presented. Based on measurements of acoustic attenuation and sound speed at two
      frequencies, it synthesizes the entire frequency dependence of the complex
      effective specific heat of the gas, which is the macroscopic "footprint" of
      relaxation effects. The algorithm is based on the fact that for a simple
      relaxation process, such as occurs in many polyatomic gases at temperatures
      around 300 K, the effective specific heat traces a semicircle in the complex
      plane as a function of frequency. Knowing the high-frequency or instantaneous
      value of the specific heat provides the capability to not only sense the
      presence, but also infer the nature and, for mixtures of unlike-symmetry
      molecules, the concentration of foreign molecules leaking in a host gas.

PMID- 16090507
TI  - Characterization of biological thin films at the solid-liquid interface by x-ray
      reflectivity.
AB  - We demonstrate that 18 keV x-rays can be used to study organic thin films at the
      solid-liquid interface by x-ray reflectivity. We establish that this is a
      powerful technique for investigating biological systems in a previously
      inaccessible manner. Our measurements enabled the density distribution of single
      phospholipid bilayer membranes in bulk water to be measured with unprecedented
      precision. Previously, characterization of biomimetic structures normal to a
      "buried" interface was a domain of neutron reflectivity.

PMID- 16090509
TI  - Communication boundaries in networks.
AB  - We investigate and quantify the interplay between topology and the ability to
      send specific signals in complex networks. We find that in a majority of
      investigated real-world networks the ability to communicate is favored by the
      network topology at small distances, but disfavored at larger distances. We
      further suggest how the ability to locate specific nodes can be improved if
      information associated with the overall traffic in the network is available.

PMID- 16090510
TI  - Comment on "Observation of optical precursors in water".

PMID- 16090511
TI  - Comment on "Frohlich mass in GaAs-based structures".

PMID- 16090580
TI  - Continuum model for polymorphism of bacterial flagella.
AB  - Bacterial flagellar filaments can abruptly change shape in response to mechanical
      load or changes in solution pH or ionic strength. These polymorphic
      transformations are an instance of a ubiquitous phenomenon, the spread of
      conformational change in large macromolecular assemblies. We propose a new theory
      for polymorphism, whose essential elements are two molecular switches and an
      elastic mismatch strain between the inner and outer cores of the filament. We
      calculate the phase diagram for helical and straight states, and the response of
      a helical filament to an external moment.

PMID- 16090581
TI  - Intrinsic low temperature paramagnetism in B-DNA.
AB  - We present an experimental study of magnetization in lambda-DNA in conjunction
      with structural measurements. The results show the surprising interplay between
      the molecular structures and their magnetic property. In the B-DNA state, lambda
      DNA exhibits paramagnetic behavior below 20 K that is nonlinear in an applied
      magnetic field whereas, in the A-DNA state, it remains diamagnetic down to 2 K.
      We propose orbital paramagnetism as the origin of the observed phenomena and
      discuss its relation to the existence of long range coherent transport in B-DNA
      at low temperature.

PMID- 16090582
TI  - From DNA sequence analysis to modeling replication in the human genome.
AB  - We explore the large-scale behavior of nucleotide compositional strand
      asymmetries along human chromosomes. As we observe for 7 of 9 origins of
      replication experimentally identified so far, the (TA+GC) skew displays rather
      sharp upward jumps, with a linear decreasing profile in between two successive
      jumps. We present a model of replication with well positioned replication origins
      and random terminations that accounts for the observed characteristic serrated
      skew profiles. We succeed in identifying 287 pairs of putative adjacent
      replication origins with an origin spacing approximately 1-2 Mbp that are likely
      to correspond to replication foci observed in interphase nuclei and recognized as
      stable structures that persist throughout subsequent cell generations.

PMID- 16090583
TI  - Predicting mutual entrainment of oscillators with experiment-based phase models.
AB  - We show that mutual entrainment in interacting oscillators can be characterized
      using phase models that are developed from direct experiments with a single
      oscillator. The models are used to predict order-disorder transitions in
      populations and the dependence of order on system parameters; the description is
      verified in independent experiments in sets of chemical oscillators. The
      experiment-based model properly describes in-phase and antiphase mutual
      entrainment with positive and negative interactions in small sets as well as
      dynamical clustering in populations of oscillators.

PMID- 16090584
TI  - Anomalous transport in scale-free networks.
AB  - To study transport properties of scale-free and Erdos-Renyi networks, we analyze
      the conductance G between two arbitrarily chosen nodes of random scale-free
      networks with degree distribution P(k)-k(-lambda) in which all links have unit
      resistance. We predict a broad range of values of G, with a power-law tail
      distribution phi(SF)(G)-G(-g(G)), where g(G)=2lambda-1, and confirm our
      predictions by simulations. The power-law tail in phi(SF)(G) leads to large
      values of G, signaling better transport in scale-free networks compared to Erdos
      Renyi networks where the tail of the conductivity distribution decays
      exponentially. Based on a simple physical "transport backbone" picture we show
      that the conductances of scale-free and Erdos-Renyi networks are well
      approximated by ck(A)k(B)/(k(A)+k(B)) for any pair of nodes A and B with degrees
      k(A) and k(B), where c emerges as the main parameter characterizing network
      transport.

PMID- 16090587
TI  - Realization of fully frustrated Josephson-junction arrays with cold atoms.
AB  - Fully frustrated Josephson-junction arrays (FF-JJA's) exhibit a subtle compound
      phase transition in which an Ising transition associated with discrete broken
      translational symmetry and a Berezinskii-Kosterlitz-Thouless transition
      associated with quasi-long-range phase coherence occur nearly simultaneously. In
      this Letter we discuss a cold-atom realization of the FF-JJA system. We
      demonstrate that both orders can be studied by standard momentum-distribution
      function measurements and present numerical results, based on a successful self
      consistent spin-wave approximation, that illustrate the expected behavior of
      observables.

PMID- 16090588
TI  - Direct observation of tunneling and nonlinear self-trapping in a single bosonic
      Josephson junction.
AB  - We report on the first realization of a single bosonic Josephson junction,
      implemented by two weakly linked Bose-Einstein condensates in a double-well
      potential. In order to fully investigate the nonlinear tunneling dynamics we
      measure the density distribution in situ and deduce the evolution of the relative
      phase between the two condensates from interference fringes. Our results verify
      the predicted nonlinear generalization of tunneling oscillations in
      superconducting and superfluid Josephson junctions. Additionally, we confirm a
      novel nonlinear effect known as macroscopic quantum self-trapping, which leads to
      the inhibition of large amplitude tunneling oscillations.

PMID- 16090589
TI  - Cold atoms in non-Abelian gauge potentials: from the Hofstadter "moth" to lattice
      gauge theory.
AB  - We demonstrate how to create artificial external non-Abelian gauge potentials
      acting on cold atoms in optical lattices. The method employs atoms with k
      internal states, and laser assisted state sensitive tunneling, described by
      unitary k x k matrices. The single-particle dynamics in the case of intense U2
      vector potentials lead to a generalized Hofstadter butterfly spectrum which shows
      a complex mothlike structure. We discuss the possibility to realize non-Abelian
      interferometry (Aharonov-Bohm effect) and to study many-body dynamics of
      ultracold matter in external lattice gauge fields.

PMID- 16090590
TI  - Non-Abelian gauge potentials for ultracold atoms with degenerate dark states.
AB  - We show that the adiabatic motion of ultracold, multilevel atoms in spatially
      varying laser fields can give rise to effective non-Abelian gauge fields if
      degenerate adiabatic eigenstates of the atom-laser interaction exist. A pair of
      such degenerate dark states emerges, e.g., if laser fields couple three internal
      states of an atom to a fourth common one under pairwise two-photon-resonance
      conditions. For this so-called tripod scheme we derive general conditions for
      truly non-Abelian gauge potentials and discuss special examples. In particular we
      show that using orthogonal laser beams with orbital angular momentum an effective
      magnetic field can be generated that has a monopole component.

PMID- 16090591
TI  - Rontgen quantum phase shift: a semiclassical local electrodynamical effect?
AB  - The Rontgen quantum phase shift is exhibited by the interference of point
      particles endowed with an electric dipole moment due to their motion relative to
      a source of the magnetic field. Here we show, using arguments involving the
      classical concepts of force and its impulse, that the Rontgen phase shift arises
      within a largely classical (semiclassical) theoretical framework. All the
      subtleties normally associated with the nonlocality of magnetic (Aharonov-Bohm
      type) quantum phase phenomena are uncontroversially absent in the classical
      treatment.

PMID- 16090592
TI  - Static and dynamic properties of trapped fermionic Tonks-Girardeau gases.
AB  - We investigate some static and dynamic properties of harmonically trapped
      fermionic Tonks-Girardeau gases in tight de Broglie waveguides with attractive p
      wave interactions induced by a Feshbach resonance. An exact solution for the one
      body density matrix is analyzed in terms of its natural orbitals, with the
      surprising result that for odd, but not for even, numbers of fermions the
      maximally occupied orbital coincides with the ground harmonic oscillator orbital.
      A dynamical consequence of this is that when the interactions are turned off the
      on-axis density remains a maximum for an odd number of fermions, whereas a
      minimum develops for an even number.

PMID- 16090593
TI  - Extracting the condensate density from projection experiments with Fermi gases.
AB  - A debated issue in the physics of the BCS-BEC crossover with trapped Fermi atoms
      is to identify characteristic properties of the superfluid phase. Recently, a
      condensate fraction was measured on the BCS side of the crossover by sweeping the
      system in a fast (nonadiabatic) way from the BCS to the Bose-Einstein
      condensation (BEC) sides, thus "projecting" the initial many-body state onto a
      molecular condensate. We analyze here the theoretical implications of these
      projection experiments, by identifying the appropriate quantum-mechanical
      operator associated with the measured quantities and relating them to the many
      body correlations occurring in the BCS-BEC crossover. Calculations are presented
      over wide temperature and coupling ranges, by including pairing fluctuations on
      top of the mean field.

PMID- 16090594
TI  - Two-loop corrections to Bhabha scattering.
AB  - The two-loop radiative photonic corrections to Bhabha scattering are computed in
      the leading order of the small electron mass expansion up to the nonlogarithmic
      term. After including the soft photon bremsstrahlung, we obtain the infrared
      finite result for the differential cross section, which can directly be applied
      to a precise luminosity determination of the present and future e+ e- colliders.

PMID- 16090595
TI  - Resource-efficient linear optical quantum computation.
AB  - We introduce a scheme for linear optics quantum computation, that makes no use of
      teleported gates, and requires stable interferometry over only the coherence
      length of the photons. We achieve a much greater degree of efficiency and a
      simpler implementation than previous proposals. We follow the "cluster state"
      measurement based quantum computational approach, and show how cluster states may
      be efficiently generated from pairs of maximally polarization entangled photons
      using linear optical elements. We demonstrate the universality and usefulness of
      generic parity measurements, as well as introducing the use of redundant encoding
      of qubits to enable utilization of destructive measurements--both features of use
      in a more general context.

PMID- 16090596
TI  - Relations between cloning and the universal NOT derived from conservation laws.
AB  - We discuss certain relations between cloning and the not operation that can be
      derived from conservation laws alone. Those relations link the limitations on
      cloning and the not operation possibly imposed by other laws of nature. Our
      result is quite general and holds both in classical and quantum-mechanical
      worlds, for both optimal and suboptimal operations, and for bosons as well as
      fermions.

PMID- 16090597
TI  - No signaling and quantum key distribution.
AB  - Standard quantum key distribution protocols are provably secure against
      eavesdropping attacks, if quantum theory is correct. It is theoretically
      interesting to know if we need to assume the validity of quantum theory to prove
      the security of quantum key distribution, or whether its security can be based on
      other physical principles. The question would also be of practical interest if
      quantum mechanics were ever to fail in some regime, because a scientifically and
      technologically advanced eavesdropper could perhaps use postquantum physics to
      extract information from quantum communications without necessarily causing the
      quantum state disturbances on which existing security proofs rely. Here we
      describe a key distribution scheme provably secure against general attacks by a
      postquantum eavesdropper limited only by the impossibility of superluminal
      signaling. Its security stems from violation of a Bell inequality.

PMID- 16090598
TI  - Universal and deterministic manipulation of the quantum state of harmonic
      oscillators: a route to unitary gates for Fock state qubits.
AB  - We present a simple quantum circuit that allows for the universal and
      deterministic manipulation of the quantum state of confined harmonic oscillators.
      The scheme is based on the selective interactions of the referred oscillator with
      an auxiliary three-level system and a classical external driving source, and
      enables any unitary operations on Fock states, two by two. One circuit is
      equivalent to a single qubit unitary logical gate on Fock states qubits.
      Sequences of similar protocols allow for complete, deterministic, and state
      independent manipulation of the harmonic oscillator quantum state.

PMID- 16090599
TI  - Chaotic properties of systems with Markov dynamics.
AB  - We present a general approach for computing the dynamic partition function of a
      continuous-time Markov process. The Ruelle topological pressure is identified
      with the large deviation function of a physical observable. We construct for the
      first time a corresponding finite Kolmogorov-Sinai entropy for these processes.
      Then, as an example, the latter is computed for a symmetric exclusion process. We
      further present the first exact calculation of the topological pressure for an N
      body stochastic interacting system, namely, an infinite-range Ising model endowed
      with spin-flip dynamics. Expressions for the Kolmogorov-Sinai and the topological
      entropies follow.

PMID- 16090600
TI  - Dark minihalos with intermediate mass black holes.
AB  - We argue that the Milky Way (MW) contains 10(3)-10(4) intermediate mass black
      holes (IMBHs) of mass approximately 10(2-3)M. Some IMBHs are naked, and some are
      enshrouded by dense dark minispikes and by minihalos of (10(6)-10(7))M circle.
      The IMBH is formed off-center by gas accretion in a minihalo. These dense
      minihalos (the nearest at about 2 kpc) survive mostly without tidal stripping by
      the MW, and are largely invisible except that their pointlike neutralino
      annihilation signals (with bolometric luminosities of 10(3-5)L circle 50 GeV /
      mChi within 0.01-0.1 pc of their centers) stand out well above the MW background
      and are more luminous than outer dwarf satellite galaxies.

PMID- 16090601
TI  - Weighing neutrinos with galaxy cluster surveys.
AB  - Large future galaxy cluster surveys, combined with cosmic microwave background
      observations, can achieve a high sensitivity to the masses of cosmologically
      important neutrinos. We show that a weak lensing selected sample of > or
      approximately 100,000 clusters could tighten the current upper bound on the sum
      of masses of neutrino species by an order of magnitude, to a level of 0.03 eV.
      Since this statistical sensitivity is below the best existing lower limit on the
      mass of at least one neutrino species, a future detection is likely, provided
      that systematic errors can be controlled to a similar level.

PMID- 16090602
TI  - Relationship between Hawking radiation and gravitational anomalies.
AB  - We show that in order to avoid a breakdown of general covariance at the quantum
      level the total flux in each outgoing partial wave of a quantum field in a black
      hole background must be equal to that of a (1+1)-dimensional blackbody at the
      Hawking temperature.

PMID- 16090603
TI  - Gravitational evolution of a perturbed lattice and its fluid limit.
AB  - We apply a simple linearization, well known in solid state physics, to
      approximate the evolution at early times of cosmological N-body simulations of
      gravity. In the limit that the initial perturbations, applied to an infinite
      perfect lattice, are at wavelengths much greater than the lattice spacing l, the
      evolution is exactly that of a pressureless self-gravitating fluid treated in the
      analogous (Lagrangian) linearization, with the Zeldovich approximation as a
      subclass of asymptotic solutions. Our less restricted approximation allows one to
      trace the evolution of the discrete distribution until the time when particles
      approach one another (i.e., "shell crossing"). We calculate modifications of the
      fluid evolution, explicitly dependent on l, i.e., discreteness effects in the N
      body simulations. We note that these effects become increasingly important as the
      initial redshift is increased at fixed l.

PMID- 16090604
TI  - Indication for primordial anisotropies in the neutrino background from the
      Wilkinson microwave anisotropy probe and the Sloan digital sky survey.
AB  - We demonstrate that combining cosmic microwave background anisotropy measurements
      from the 1st year Wilkinson Microwave Anisotropy Probe observations with
      clustering data from the Sloan galaxy redshift survey yields an indication for
      primordial anisotropies in the cosmological neutrino background.

PMID- 16090606
TI  - Quantum electrodynamics for vector mesons.
AB  - Quantum electrodynamics for rho mesons is considered. It is shown that, at the
      tree level, the value of the gyromagnetic ratio of the rho+ is fixed to 2 in a
      self-consistent effective quantum field theory. Further, the mixing parameter of
      the photon and the neutral vector meson is equal to the ratio of electromagnetic
      and strong couplings, leading to the mass difference M(rho0)-M(rho+/-)
      approximately 1 MeV at tree order.

PMID- 16090607
TI  - Solving the leading-order evolution equation for generalized parton
      distributions.
AB  - An analytic method for the solution of the evolution equation for generalized
      parton distributions (GPDs) is presented. The small x, xi asymptotics of GPDs are
      calculated.

PMID- 16090608
TI  - Strange-quark mass from tau-lepton decays with O(alpha3s) accuracy.
AB  - The first complete calculation of the quadratic quark mass correction to the
      correlator of the two currents relevant for the strangeness-changing semihadronic
      tau-decay rate is presented including its real part at the four-loop level. This
      allows us to perform the extraction of the strange-quark mass m(s) from the decay
      width of the tau-lepton with full O(alpha3s) accuracy. In agreement with previous
      estimates, the newly computed alpha3s term proves to be rather large. This
      justifies inclusion of the similarly estimated alpha4s term in phenomenological
      analysis. Combined with an updated value of V us and an "improved" version of the
      renormalization group improvement of the perturbative series, this leads to an
      increase of the central value of m(s) by about 20% and a partial reduction of the
      theoretical uncertainty by about 50%.

PMID- 16090609
TI  - Observation of different azimuthal emission patterns of K+ and of K- mesons in
      heavy-ion collisions at 1-2 A GeV.
AB  - Azimuthal distributions of pi+, K+, and K- mesons have been measured in Au+Au
      reactions at 1.5A GeV and Ni+Ni reactions at 1.93 A GeV. In semicentral
      collisions at midrapidity, pi+ and K+ mesons are emitted preferentially
      perpendicular to the reaction plane in both collision systems. In contrast for K-
      mesons in Ni+Ni reactions, an in-plane elliptic flow was observed for the first
      time at these incident energies.

PMID- 16090610
TI  - Attosecond electron wave packet dynamics in strong laser fields.
AB  - We use a train of sub-200 attosecond extreme ultraviolet (XUV) pulses with
      energies just above the ionization threshold in argon to create a train of
      temporally localized electron wave packets. We study the energy transfer from a
      strong infrared (IR) laser field to the ionized electrons as a function of the
      delay between the XUV and IR fields. When the wave packets are born at the zero
      crossings of the IR field, a significant amount of energy (approximately 20 eV)
      is transferred from the field to the electrons. This results in dramatically
      enhanced above-threshold ionization in conditions where the IR field alone does
      not induce any significant ionization. Because both the energy and duration of
      the wave packets can be varied independently of the IR laser, they are valuable
      tools for studying and controlling strong-field processes.

PMID- 16090611
TI  - Idempotency-conserving iteration scheme for the one-electron density matrix.
AB  - For the first order density matrix P of a noninteracting N-electron problem, an
      iterative formula is presented that preserves the trace and idempotency of P so
      that no purification is needed. Hermiticity--which may be slightly violated in
      the course of the iteration--gets restored when the iteration converges and the
      converged P corresponds to the exact solution. For sparse P, the energy is
      obtained by an O(N) procedure that needs no prior knowledge of the chemical
      potential. Illustrative calculations in tight-binding and ab initio Hartree-Fock
      levels are presented.

PMID- 16090612
TI  - Direct measurement of the radiative lifetime of vibrationally excited OH
      radicals.
AB  - Neutral molecules, isolated in the gas phase, can be prepared in a long-lived
      excited state and stored in a trap. The long observation time afforded by the
      trap can then be exploited to measure the radiative lifetime of this state by
      monitoring the temporal decay of the population in the trap. This method is
      demonstrated here and used to benchmark the Einstein A coefficients in the Meinel
      system of OH. A pulsed beam of vibrationally excited OH radicals is Stark
      decelerated and loaded into an electrostatic quadrupole trap. The radiative
      lifetime of the upper Lamda-doublet component of the Chi2Pi3/2, v=1, J=3/2 level
      is determined as 59.0+/-2.0 ms, in good agreement with the calculated value of
      58.0+/-1.0 ms.

PMID- 16090613
TI  - State-to-state dynamics of high-n Rydberg H-atom scattering with D2.
AB  - Full quantum-state resolved scattering of a highly excited Rydberg H atom with D2
      has been carried out using the Rydberg H-atom time-of-flight method. A detailed
      analysis of the experimental results shows that both inelastic and reactive
      scatterings are significant in the Hn-D2 collisions, and nuclear spin is
      conserved in the inelastic scattering process. The differential cross sections
      for the Hn-D2 reaction measured in this work are then compared with the results
      for the H+ reaction with D2 in an ion beam scattering experiment. The remarkable
      agreement between the two experiments suggests that the Fermi independent
      collider model is valid even at the full quantum state-to-state scattering level,
      providing a promising tool for investigating the state-to-state dynamics of
      certain elementary ion-molecule reactions.

PMID- 16090614
TI  - Coulomb stability limit of highly charged Cq+60 fullerenes.
AB  - We perform density functional theory calculations of Cq+60 and Cq+58 fullerenes
      as well as of transition states related to dissociation of Cq+60 into Cq-s(+)58
      and C(s+)2 for charges q=0-14. For q< or =8, the lowest fission barrier
      corresponds to C+2 emission, whereas, for higher q values, the lowest barrier
      corresponds to the emission of two atomic fragments [2C]s+ with s> or =2. We
      conclude that the Coulomb stability limit corresponds to q=14.

PMID- 16090615
TI  - Phase effects in the diffraction of light: beyond the grating equation.
AB  - Diffraction gratings affect the absolute phase of light in a way that is not
      obvious from the usual derivation of optical paths using the grating equation.
      For example, consider light which encounters first one and then the second of two
      parallel gratings. If one grating is moved parallel to its surface, the phase of
      the light diffracted from the grating pair is shifted by 2pi each time the
      grating is moved by one grating constant, even though the geometric path length
      is not altered by the motion. This additional phase shift must be included when
      incorporating diffraction gratings in interferometers.

PMID- 16090616
TI  - Generalized nonlinear Schrodinger equation for dispersive susceptibility and
      permeability: application to negative index materials.
AB  - A new generalized nonlinear Schrodinger equation describing the propagation of
      ultrashort pulses in bulk media exhibiting frequency dependent dielectric
      susceptibility and magnetic permeability is derived and used to characterize wave
      propagation in a negative index material. The equation has new features that are
      distinct from ordinary materials (mu=1): the linear and nonlinear coefficients
      can be tailored through the linear properties of the medium to attain any
      combination of signs unachievable in ordinary matter, with significant potential
      to realize a wide class of solitary waves.

PMID- 16090617
TI  - Critical behavior of light in mode-locked lasers.
AB  - Light is shown to exhibit critical and tricritical behavior in passively mode
      locked lasers with externally injected pulses. It is a first and unique example
      of critical phenomena in a one-dimensional many-body light-mode system. The phase
      diagrams consist of regimes with continuous wave, driven parapulses, spontaneous
      pulses via mode condensation, and heterogeneous pulses, separated by phase
      transition lines that terminate with critical or tricritical points. Enhanced non
      Gaussian fluctuations and collective dynamics are present at the critical and
      tricritical points, showing a mode system analog of the critical opalescence
      phenomenon. The critical exponents are calculated and shown to comply with the
      mean field theory, which is rigorous in the light system.

PMID- 16090618
TI  - Controlling the spontaneous emission rate of single quantum dots in a two
      dimensional photonic crystal.
AB  - We observe large spontaneous emission rate modification of individual InAs
      quantum dots (QDs) in a 2D photonic crystal with a modified, high-Q single-defect
      cavity. Compared to QDs in a bulk semiconductor, QDs that are resonant with the
      cavity show an emission rate increase of up to a factor of 8. In contrast, off
      resonant QDs indicate up to fivefold rate quenching as the local density of
      optical states is diminished in the photonic crystal. In both cases, we
      demonstrate photon antibunching, showing that the structure represents an on
      demand single photon source with a pulse duration from 210 ps to 8 ns. We explain
      the suppression of QD emission rate using finite difference time domain
      simulations and find good agreement with experiment.

PMID- 16090619
TI  - Repulsive synchronization in an array of phase oscillators.
AB  - We study the dynamics of a repulsively coupled array of phase oscillators. For an
      array of globally coupled identical oscillators, repulsive coupling results in a
      family of synchronized regimes characterized by zero mean field. If the number of
      oscillators is sufficiently large, phase locking among oscillators is destroyed,
      independently of the coupling strength, when the oscillators' natural frequencies
      are not the same. In locally coupled networks, however, phase locking occurs even
      for nonidentical oscillators when the coupling strength is sufficiently strong.

PMID- 16090620
TI  - Localized turbulent flows on scouring granular beds.
AB  - In many applications a sustained, localized turbulent flow scours a cohesionless
      granular bed to form a pothole. Here we use similarity methods to derive a
      theoretical formula for the equilibrium depth of the pothole. Whereas the
      empirical formulas customarily used in applications contain numerous free
      exponents, the theoretical formula contains a single one, which we show can be
      determined via the phenomenological theory of turbulence. Our derivation affords
      insight into how a state of dynamic equilibrium is attained between a granular
      bed and a localized turbulent flow.

PMID- 16090621
TI  - Gas-nanoparticle scattering: a molecular view of momentum accommodation function.
AB  - We examine the origin of diffuse gas-particle scattering by molecular dynamics
      simulation and show that diffuse scattering is the consequence of gas molecule
      trapping on the particle surface. Trapping occurs because of gas-particle
      interactions and the particle's ability of energy accommodation. These
      observations explain the transition from specular-to-diffuse scattering as the
      particle size becomes larger than the molecular size. We discuss the implication
      of this transition on the transport properties of nanometer-size particles.

PMID- 16090605
TI  - Branching fraction and CP asymmetries of B0-->K0(S)K0(S)K0(S).
AB  - We present measurements of the branching fraction and time-dependent CP-violating
      asymmetries in B0-->K0(S)K0(S)K0(S) decays based on 227 x 10(6) Upsilon4S-->BB
      decays collected with the BABAR detector at the PEP-II asymmetric-energy B
      factory at SLAC. We obtain a branching fraction of (6.9(+0.9)(-0.8)+/-0.6) x 10(
      6), and CP asymmetries C=-0.34(+0.28)(-0.25)+/-0.05 and S=-0.71(+0.38)(-0.32)+/
      0.04, where the first uncertainties are statistical and the second systematic.

PMID- 16090622
TI  - Large scale dissipation and filament instability in two-dimensional turbulence.
AB  - Coherent vortices in two-dimensional turbulence induce far-field effects that
      stabilize vorticity filaments and inhibit the generation of new vortices. We show
      that the large-scale energy sink often included in numerical simulations of
      statistically stationary two-dimensional turbulence reduces the stabilizing role
      of the vortices, leading to filament instability and to continuous formation of
      new coherent vortices. This counterintuitive effect sheds new light on the
      mechanisms responsible for vortex formation in forced-dissipated two-dimensional
      turbulence, and it has significant impact on the temporal evolution of the vortex
      population in freely decaying turbulence. The time dependence of vortex
      statistics in the presence of a large-scale energy sink can be approximately
      described by a modified version of the scaling theory developed for small-scale
      dissipation.

PMID- 16090623
TI  - Grad-Shafranov equilibria with negative core toroidal current in Tokamak plasmas.
AB  - Numerical Grad-Shafranov (GS) equilibria with negative current density in the
      plasma core are computed which do not impose any particularly chosen models for
      the pressure and current-density profiles. This flexibility allows the profiles
      to be tailored so that an island unfolds in the low-field side, even for
      elongated plasmas, thus sustaining the negative-current core against outward
      forces. Among other topological results, reversed GS equilibria are also shown to
      be necessarily non-nested, except for the cylindrical and other very special
      degenerate, hence structurally unstable cases.

PMID- 16090624
TI  - Asymptotic evolution of weakly collisional Vlasov-Poisson plasmas.
AB  - We study the role of (weak) numerical diffusion on the long time evolution of the
      Vlasov-Poisson plasma. We consider the classical problem of phase space vortex
      formation by particle trapping. We show that the asymptotic macroscopic state is
      not independent of diffusion even if the dissipative length scale is much shorter
      than any characteristic physical length scale of the system.

PMID- 16090625
TI  - Experimental observation of a periodically oscillating plasma sphere in a gridded
      inertial electrostatic confinement device.
AB  - The periodically oscillating plasma sphere (POPS) [D. C. Barnes and R. A. Nebel,
      Phys. Plasmas 5, 2498 (1998).] oscillation has been observed in a gridded
      inertial electrostatic confinement device. In these experiments, ions in the
      virtual cathode exhibit resonant behavior when driven at the POPS frequency.
      Excellent agreement between the observed POPS resonance frequency and theoretical
      predictions has been observed for a wide range of potential well depths and for
      three different ion species. The results provide the first experimental
      validation of the POPS concept proposed by Barnes and Nebel [R. A. Nebel and D.
      C. Barnes, Fusion Technol. 34, 28 (1998).].

PMID- 16090626
TI  - Ion-pressure equations derived from measurements in space.
AB  - Cluster measurements at the bow shock, the magnetosheath, and the magnetospheric
      boundary layer are used to derive ion-pressure equations for hot anisotropic
      plasmas. It is demonstrated that both perpendicular and parallel ion pressures
      are well approximated by polybaric expressions is proportional to
      N(gamma)B(kappa), where N is the plasma density, B is the magnetic field, gamma
      is in the range 0.5 to 2, and kappa is between -2 and 0. The parameters derived
      from observations are distinctively different from those predicted by double
      adiabatic theory and are shown to hold for pressure variations over 4 orders of
      magnitude and for a range of plasma beta (ratio of kinetic/magnetic pressures)
      between 10(-4) and 10. The results are relevant for simulations and theories of
      astrophysical, solar, interplanetary, and magnetospheric processes based on MHD
      equations.

PMID- 16090627
TI  - Lattice response of quantum solids to an impulsive local perturbation.
AB  - The lattice response of solid para-H2 to an impulsive electronic excitation was
      studied using femtosecond pump-probe spectroscopy. The evolution of an electronic
      bubble in the crystal, created upon excitation of the A(3ssigma) Rydberg state of
      an NO impurity, was followed in real time, with a resolution of 100 fs. The
      experimental results, interpreted in connection with molecular dynamics
      simulations with quantum corrections, indicate the presence of three stages in
      the dynamics: a sub-100 fs "adiabatic" phase, a 0.5-1 ps phase, corresponding to
      the interaction of the first with the next shells driven by the bubble expansion,
      and a 5 ps phase, corresponding to a slow rearrangement of the environment
      surrounding the impurity. These findings indicate that the lattice response in
      solid para-H2 resembles that of a liquid.

PMID- 16090628
TI  - Temperature-dependent energy thresholds for ion-stimulated defect formation in
      solids.
AB  - Recent simulations and experiments have hinted that the solid temperature may
      affect the dynamics of defect formation when the energies of bombarding ions fall
      below about 100 eV. The present work offers direct experimental confirmation of
      this phenomenon through measurements of the energy thresholds for ion-enhanced
      surface diffusion of indium on silicon and germanium, where transport rates
      depend upon surface defect formation. Such temperature-dependent energy
      thresholds may offer a new means for modulating sputtering and defect formation
      in a variety of ion processing applications.

PMID- 16090629
TI  - Dynamic instability in intergranular fracture.
AB  - A molecular-dynamics model for crack propagation under steady-state conditions is
      used to study dynamic instabilities along a grain boundary in aluminum that occur
      when the crack speed approaches 1/3 of the material's Rayleigh wave speed.
      Instead of crack branching, as is characteristic for a crack propagating in a
      homogeneous environment, the instability of an intergranular crack results in a
      periodic series of dislocation bursts. These bursts limit the crack speed and
      produce velocity oscillations with a large increase in energy dissipation that
      increases the grain boundary toughness.

PMID- 16090630
TI  - Singular point of a system of Lennard-Jones particles at negative pressures.
AB  - The method of molecular dynamics is used in a system of 2048 Lennard-Jones
      particles to determine the spinodal of a stretched liquid and crystal and the
      lines of their phase equilibrium at negative pressures. It is shown that a
      metastable extension of the melting line does not reach the zero isotherm, and
      ends on the spinodal of a stretched liquid. The point of termination of
      metastable liquid-crystal phase equilibrium is the singular point at a
      thermodynamic surface of states.

PMID- 16090631
TI  - Subdiffusion and dynamical heterogeneities in a lattice glass model.
AB  - We study a kinetically constrained lattice glass model in which continuous local
      densities are randomly redistributed on neighboring sites with a kinetic
      constraint that inhibits the process at high densities, and a random bias
      accounting for attractive or repulsive interactions. The full steady-state
      distribution can be computed exactly in any space dimension d. Dynamical
      heterogeneities are characterized by a length scale that diverges when
      approaching the critical density. The glassy dynamics of the model can be
      described as a reaction-diffusion process for the mobile regions. The motion of
      mobile regions is found to be subdiffusive, for a large range of parameters, due
      to a self-induced trapping mechanism.

PMID- 16090632
TI  - Tuning diffusion and friction in microscopic contacts by mechanical excitations.
AB  - We demonstrate that lateral vibrations of a substrate can dramatically increase
      surface diffusivity and mobility and reduce friction at the nanoscale. Dilatancy
      is shown to play an essential role in the dynamics of a nanometer-size tip which
      interacts with a vibrating surface. We find an abrupt dilatancy transition from
      the state with a small tip-surface separation to the state with a large
      separation as the vibration frequency increases. Atomic force microscopy
      experiments are suggested which can test the predicted effects.

PMID- 16090633
TI  - Hysteresis, force oscillations, and nonequilibrium effects in the adhesion of
      spherical nanoparticles to atomically smooth surfaces.
AB  - Equilibrium and nonequilibrium aspects of particle adsorption on the walls of
      fluid-filled nanochannels are examined via molecular dynamics simulations. The
      force on the particle and the free energy of the system are found to depend on
      the particle's history (hysteresis), in addition to its radial position and the
      wetting properties of the fluid, even when the particle moves quasistatically.
      The hysteresis is associated with changes in the fluid density in the gap between
      the particle and the wall, which persist over surprisingly long times. The force
      and free energy exhibit large oscillations with distance when the lattice of the
      structured nanoparticle is held in register with that of the tube wall, but not
      if the particle is allowed to rotate freely. Adsorbed particles are trapped in
      free-energy minima in equilibrium but can desorb if forced along the channel.

PMID- 16090634
TI  - Temperature dependent weak field Hall resistance in two-dimensional carrier
      systems.
AB  - Using the Drude-Boltzmann semiclassical transport theory, we calculate the weak
      field Hall resistance of a two-dimensional system at low densities and
      temperatures, assuming carrier scattering by screened random charged impurity
      centers. The temperature-dependent 2D Hall coefficient shows striking
      nonmonotonicity in strongly screened systems, and, in particular, we
      qualitatively explain the recent puzzling experimental observation of a
      decreasing Hall resistance with increasing temperature in a dilute 2D hole
      system. We predict that the impurity scattering limited Hall coefficient will
      eventually increase with temperature at higher temperatures.

PMID- 16090635
TI  - Understanding the heavy fermion phenomenology from a microscopic model.
AB  - We solve the 3D periodic Anderson model using a two impurity cluster dynamical
      mean field theory. We obtain the temperature versus hybridization phase diagram.
      Approaching the quantum critical point (QCP) both the Neel and lattice Kondo
      temperatures decrease and they do not cross at the lowest temperature we reached.
      While strong ferromagnetic spin fluctuation on the Kondo side is observed, our
      result suggests the critical static spin susceptibility is local in space at the
      QCP. We observe in the crossover region a logarithmic temperature dependence in
      the specific heat coefficient and spin susceptibility.

PMID- 16090636
TI  - Nonexponential quasiparticle decay and phase relaxation in low-dimensional
      conductors.
AB  - We show that in low-dimensional disordered conductors, the quasiparticle decay
      and the relaxation of the phase are not exponential processes. In the quasi-one
      dimensional case, both behave at small time as e(-(t/tau(in))3/2) where the
      inelastic time, tau(in), identical for both processes, is a power T-2/3 of the
      temperature. The nonexponential quasiparticle decay results from a modified
      derivation of the Fermi golden rule. This result implies the existence of an
      unusual distribution of relaxation times.

PMID- 16090637
TI  - Origin of charge density wave formation in insulators from a high resolution
      photoemission study of BaIrO3.
AB  - We investigate the origin of charge density wave (CDW) formation in insulators by
      studying BaIrO3 using high-resolution (1.4 meV) photoemission spectroscopy. The
      spectra reveal the existence of localized density of states at the Fermi level,
      E(F), in the vicinity of room temperature. These localized states are found to
      vanish as the temperature is lowered, thereby, opening a soft gap at E(F), as a
      consequence of CDW transition. In addition, the energy dependence of the spectral
      density of states reveals the importance of magnetic interactions, rather than
      well-known Coulomb repulsion effect, in determining the electronic structure
      thereby implying a close relationship between ferromagnetism and CDW observed in
      this compound. Also, Ba core level spectra surprisingly exhibit an unusual
      behavior prior to CDW transition.

PMID- 16090638
TI  - Stability of Fermi surfaces and K theory.
AB  - Nonrelativistic Fermi liquids in d+1 dimensions exhibit generalized Fermi
      surfaces: (d-p)-dimensional submanifolds in the (k,omega)-space supporting
      gapless excitations. We show that the universality classes of stable Fermi
      surfaces are classified by K theory, with the pattern of stability determined by
      Bott periodicity. The Atiyah-Bott-Shapiro construction implies that the low
      energy modes near a Fermi surface exhibit relativistic invariance in the
      transverse p+1 dimensions. This suggests an intriguing parallel between
      nonrelativistic Fermi liquids and D-branes of string theory.

PMID- 16090639
TI  - Perturbing the superconducting planes in CeCoIn5 by Sn substitution.
AB  - In contrast to substitution on the Co or Ce site, Sn substitution has a
      remarkably strong effect on superconductivity in CeCoIn5-xSnx, with Tc-->0 beyond
      only 3.6% Sn. Instead of being randomly distributed on in-plane and out-of-plane
      In sites, extended x-ray absorption fine structure measurements show the Sn atoms
      preferentially substitute within the Ce-In plane. This result highlights the
      importance of the In1 site to impurity scattering and clearly demonstrates the
      two-dimensional nature of superconductivity in CeCoIn5.

PMID- 16090640
TI  - Magnetization noise in magnetoelectronic nanostructures.
AB  - By scattering theory we show that spin current noise in normal electric
      conductors in contact with nanoscale ferromagnets increases the magnetization
      noise by means of a fluctuating spin-transfer torque. Johnson-Nyquist noise in
      the spin current is related to the increased Gilbert damping due to spin pumping,
      in accordance with the fluctuation-dissipation theorem. Spin current shot noise
      in the presence of an applied bias is the dominant contribution to the
      magnetization noise at low temperatures.

PMID- 16090641
TI  - Photoinduced charge transfer across the interface between organic molecular
      crystals and polymers.
AB  - Photoinduced charge transfer of positive and negative charges across the
      interface between a single-crystal organic semiconductor and a polymeric
      insulator is observed in electric field-effect experiments. Immobilization of the
      transferred charge by deep traps in the polymer results in a shift of the
      threshold of field-induced conductivity along the semiconductor-polymer
      interface, which allows for direct measurements of the charge transfer rate. The
      transfer occurs when the photon energy exceeds the absorption edge of the
      semiconductor. The direction of the transverse electric field at the interface
      determines the sign of the transferred charge; the transfer rate is controlled by
      the field magnitude and light intensity.

PMID- 16090642
TI  - Intrinsic spin Hall effect in the two-dimensional hole gas.
AB  - We show that two types of spin-orbit coupling in the 2 dimensional hole gas, with
      and without inversion symmetry breaking, contribute to the intrinsic spin-Hall
      effect. Furthermore, the vertex correction due to impurity scattering vanishes in
      both cases, in sharp contrast to the case of usual Rashba coupling in the
      electron band. Recently, the spin-Hall effect in a hole doped GaAs semiconductor
      has been observed experimentally by Wunderlich et al. [ Phys. Rev. Lett. 94,
      047204 (2005).]. From the fact that the lifetime broadening is smaller than the
      spin splitting, and the fact impurity vertex corrections vanish in this system,
      we argue that the observed spin-Hall effect should be in the intrinsic regime.

PMID- 16090643
TI  - Magnetic-field-dependent carrier injection at La2/3Sr1/3MnO3/ and organic
      semiconductors interfaces.
AB  - We have fabricated organic diodes utilizing several pi-conjugated organic
      semiconductors (OSEC) as spacer layers between La2/3Sr1/3MnO3 (LSMO) and various
      metallic electrodes, and measured their magnetoresistance (MR) and
      magnetoelectroluminescence (MEL) responses. The devices exhibit large negative
      high-field MR responses that resemble the MR response of the LSMO electrode, but
      amplified by approximately 3 orders in the resistance, and accompanied by a
      positive high-field MEL effect. These magnetic-field effects result from enhanced
      carrier injection at the LSMO-OSEC interface that is attributed to the anomalous
      field-dependent Fermi level shift in LSMO.

PMID- 16090644
TI  - Evidence for universal signatures of Zeeman-splitting-limited pseudogaps in
      superconducting electron- and hole-doped cuprates.
AB  - We probe the "normal" state in electron-doped (n-type) Sm2-xCexCuO4-delta through
      interlayer tunneling transport in magnetic fields up to 45 T. The behavior of
      intrinsic high-field c-axis negative magnetoresistance (MR), which is accessed in
      small 30 nm-high mesa structures, is characteristic of the pseudogap state. It
      follows a universal correlation between the excess low-energy dissipation due to
      the pseudogap and its closing field Hpg and is in close correspondence with the
      hole-doped (p-type) Bi2Sr2CaCu2O8+y. The MR in the mesas and in the bulk crystals
      consistently gives a Zeeman relation between the pseudogap temperature T* and its
      closing field, pointing to a preeminent role of spin-singlet correlations in
      forming the pseudogap in cuprates, regardless of their n or p type.

PMID- 16090645
TI  - Coherent multiple charge transfer in a superconducting NbN tunnel junction.
AB  - We measured shot noise and submillimeter-wave response in a superconducting NbN
      tunnel junction that had a subharmonic gap structure on the current-voltage (I-V)
      curve. We found that the observed effective charge, defined from the noise
      current ratio, tends to a steplike function of voltage. In the presence of
      submillimeter-wave radiation of frequency v, novel step structures spaced by
      hv/2e below and above the half-gap voltage clearly appeared on the I-V curve,
      overlapping the ordinary photon-assisted tunneling steps spaced by hv/e.
      Observation of these features provides clear evidence that coherent multiple
      Andreev reflection processes occur in the NbN tunnel junction with low barrier
      transparency.

PMID- 16090646
TI  - Direct observation of a nonmonotonic dx2-y2- wave superconducting gap in the
      electron-doped high-Tc superconductor Pr0.89LaCe0.11CuO4.
AB  - We performed high-resolution angle-resolved photoemission spectroscopy on
      electron-doped high-Tc superconductor Pr0.89LaCe0.11CuO4 to study the anisotropy
      of the superconducting gap. The observed momentum dependence is basically
      consistent with the dx2-y2- wave symmetry, but obviously deviates from the
      monotonic dx2-y2- gap function. The maximum gap is observed not at the zone
      boundary, but at the hot spot where the antiferromagnetic spin fluctuation
      strongly couples to the electrons on the Fermi surface. The present experimental
      results suggest the spin-mediated pairing mechanism in electron-doped high-Tc
      superconductors.

PMID- 16090647
TI  - Edge currents in superconductors with a broken time-reversal symmetry.
AB  - We analyze edge currents and edge bands at the surface of a time-reversal
      symmetry breaking dx2-y2 + id(xy) superconductor. We show that the currents have
      large Friedel oscillations with two interfering frequencies: square root of 2kF
      from subgap states, and 2kF from the continuum. The results are based
      independently on a self-consistent slave-boson mean-field theory for the t-J
      model on a triangular lattice, and on a T-matrix scattering theory calculation.
      The shape of the edge-state band, as well as the particular frequency square root
      of 2kF of the Friedel oscillations, are attributes unique for the dx2-y2 + id(xy)
      case, and may be used as a fingerprint for its identification. Extensions to
      different time-reversal symmetry breaking superconductors can be achieved within
      the same approach.

PMID- 16090648
TI  - High temperature ferromagnetism in GaAs-based heterostructures with Mn delta
      doping.
AB  - We show that suitably designed magnetic semiconductor heterostructures consisting
      of Mn delta (delta)-doped GaAs and p-type AlGaAs layers, in which the locally
      high concentration of magnetic moments of Mn atoms are controllably overlapped
      with the two-dimensional hole gas wave function, realized remarkably high
      ferromagnetic transition temperatures (T(C)). A significant reduction of
      compensative Mn interstitials by varying the growth sequence of the structures
      followed by low-temperature annealing led to high T(C) up to 250 K. The
      heterostructure with high T(C) exhibited peculiar anomalous Hall effect behavior,
      whose sign depends on temperature.

PMID- 16090649
TI  - Bound on anisotropy in itinerant ferromagnets from random impurities.
AB  - We calculate the anisotropy energy of a single-domain ferromagnetic particle in
      which the only source of anisotropy is the presence of nonmagnetic impurities.
      Such anisotropy has easy-axis and easy-plane contributions, with random
      orientations of the axes. Typically the anisotropy energy is of order
      N1/2plankv/tau(so), where N is the number of electrons in the ferromagnetic
      particle and tau(so) is the spin-orbit time.

PMID- 16090650
TI  - Colossal magnetoresistance by avoiding a ferromagnetic state in the Mott system
      Ca3Ru2O7.
AB  - Transport and magnetic studies of Ca3Ru2O7 for temperatures ranging from 0.4 to
      56 K and magnetic fields B up to 45 T lead to strikingly different behavior when
      the field is applied along the different crystal axes. A ferromagnetic (FM) state
      with full spin polarization is achieved for the B//a axis, but colossal
      magnetoresistance is realized only for the B//b axis. For the B//c axis,
      Shubnikov-de Haas oscillations are observed and followed by a less resistive
      state than that for B//a. Hence, in contrast with standard colossal
      magnetoresistive materials, the FM phase is the least favorable for electron
      hopping. These properties together with highly unusual spin-charge-lattice
      coupling near the Mott transition (48 K) are driven by the orbital degrees of
      freedom.

PMID- 16090651
TI  - Antiferromagnetic s-d exchange coupling in GaMnAs.
AB  - Measurements of coherent electron spin dynamics in Ga1-xMnxAs/Al0.4Ga0.6As
      quantum wells with 0.0006%<x<0.03% show an antiferromagnetic (negative) exchange
      between s-like conduction band electrons and electrons localized in the d shell
      of the Mn2+ impurities. The magnitude of the s-d exchange parameter, N0alpha,
      varies as a function of well width indicative of a large and negative
      contribution due to kinetic exchange. In the limit of no quantum confinement,
      N0alpha extrapolates to -0.09+/-0.03 eV indicating that antiferromagnetic s-d
      exchange is a bulk property of GaMnAs. Measurements of the polarization-resolved
      photoluminescence show strong discrepancy from a simple model of the exchange
      enhanced Zeeman splitting, indicative of additional complexity in the exchange
      split valence band.

PMID- 16090652
TI  - Magnetoelastic coupling in the spin-dimer system TlCuCl3.
AB  - Based on high-resolution measurements of the thermal expansion and the
      magnetostriction we analyze the magnetoelastic coupling of TlCuCl3. We find that
      the phase boundary between the low-field spin liquid phase and the magnetic-field
      induced Neel phase is extremely sensitive to pressure and would change by about
      +/-185%/GPa depending on the direction of uniaxial pressure. This drastic effect
      can unambiguously be traced back to the pressure dependencies of the intradimer
      coupling, whereas changes of the interdimer couplings under pressure play a minor
      role. The observed strong decrease of the interdimer coupling, when Tl is
      substituted by K, is therefore not a consequence of chemical pressure.

PMID- 16090653
TI  - Quantum correction to conductivity close to a ferromagnetic quantum critical
      point in two dimensions.
AB  - We study the temperature dependence of the conductivity due to quantum
      interference processes for a two-dimensional disordered itinerant electron system
      close to a ferromagnetic quantum critical point. Near the quantum critical point,
      the crossover between diffusive and ballistic regimes of quantum interference
      effects occurs at a temperature T*=1/taugamma(E(F)tau)2, where gamma is the
      parameter associated with the Landau damping of the spin fluctuations, tau is the
      impurity scattering time, and E(F) is the Fermi energy. For a generic choice of
      parameters, T* is smaller than the nominal crossover scale 1/tau. In the
      ballistic quantum critical regime, the conductivity behaves as T1/3.

PMID- 16090654
TI  - Electron spin resonance in sine-gordon spin chains in the perturbative spinon
      regime.
AB  - We report the low-temperature multifrequency ESR studies of copper pyrimidine
      dinitrate, a spin-1/2 antiferromagnetic chain with alternating g tensor and the
      Dzyaloshinskii-Moriya interaction, allowing us to test a new theoretical concept
      proposed recently by Oshikawa and Affleck [Phys. Rev. Lett. 82, 5136 (1999)].
      Their theory, based on bosonization and self-energy formalism, can be applied for
      precise calculation of ESR parameters of S=1/2 antiferromagnetic chains in the
      perturbative spinon regime. Excellent quantitative agreement between the
      theoretical predictions and experiment is obtained.

PMID- 16090655
TI  - Isotope engineering of carbon nanotube systems.
AB  - The synthesis of a unique isotope engineered system, double-wall carbon nanotubes
      with natural carbon outer and highly 13C enriched inner walls, is reported from
      isotope enriched fullerenes encapsulated in single-wall carbon nanotubes
      (SWCNTs). The material allows the observation of the D line of the highly defect
      free inner tubes that can be related to a curvature induced enhancement of the
      electron-phonon coupling. Ab initio calculations explain the inhomogeneous
      broadening of inner tube Raman modes due to the distribution of different
      isotopes. Nuclear magnetic resonance shows a significant contrast of the isotope
      enriched inner SWCNTs compared to other carbon phases and provides a macroscopic
      measure of the inner tube mass content. The high curvature of the small diameter
      inner tubes manifests in an increased distribution of the chemical shift tensor
      components.

PMID- 16090656
TI  - Single quantum dot coupled to a scanning optical antenna: a tunable superemitter.
AB  - The interaction of a single quantum dot with a bowtie antenna is demonstrated for
      visible light. The antenna is generated at the apex of a Si3N4 atomic force
      microscopy tip by focused ion beam milling. When scanned over the quantum dot,
      its photoluminescence is enhanced while its excited-state lifetime is decreased.
      Our observations demonstrate that the relaxation channels of a single quantum
      emitter can be controlled by coupling to an efficiently radiating metallic
      nanoantenna.

PMID- 16090657
TI  - Microscopic measurement of photon echo formation in groups of individual
      excitonic transitions.
AB  - The third-order polarization emitted from groups of individual localized
      excitonic transitions after pulsed optical excitation is measured. We observe the
      evolution of the nonlinear response from the case of a free polarization decay
      for a single transition, to that of a photon echo for many transitions. The echo
      is shown to arise from the mutual rephasing of the emission from individual
      transitions.

PMID- 16090658
TI  - Persistent and reversible all-optical phase control in a manganite thin film.
AB  - Persistent and reversible optical phase control has been achieved in a manganite
      thin film through a careful choice of the composition of Pr1-x(Ca1-ySr(y))xMnO3
      near a multicritical point. Pulsed laser light brings the lower temperature
      metallic phase out of the higher temperature charge-ordered insulator, while a cw
      light reverses the effect by heating. We clearly demonstrate the two competing
      roles played by light, heating, and excitation across the charge gap, which are
      important in both the application and the understanding of the physics of
      electron correlation.

PMID- 16090659
TI  - Crystallization of confined non-Brownian spheres by vibrational annealing.
AB  - We introduce an experimental method to crystallize ensembles of non-Brownian
      spheres confined in narrow containers. The method is based on programmed
      vibrations and a cooling procedure (annealing). Starting with a granular gas, the
      system slowly relaxes into a solid ordered structure: Body-centered-tetragonal
      and face-centered-cubic single crystals are obtained depending on the dimensions
      of the capillaries. Dry and lubricated beads behave differently, indicating that
      a sticking coefficient between the particles is important in the dynamics of the
      crystallization.

PMID- 16090660
TI  - Broadband absorption spectroscopy via excitation of lossy resonance modes in thin
      films.
AB  - It is shown that broadband absorption spectroscopy utilizing thin lossy film
      configurations can be optimally facilitated when applied to metallic and
      insulating materials. For metallic films, the zero-order highly lossy resonance
      mode, characterized by ultra wideband absorption behavior under normal incidence,
      can be shifted, under parallel-polarization oblique incidence, toward a narrow
      band light-wavelength surface plasmon resonance condition. Higher order low-loss
      modes, however, occur in thin insulating films, exhibiting Debye relaxation
      behavior, typical for many aqueous solutions and biological substances. They can
      be excited in a highly scalable and sensitive manner in various frequency bands,
      between light and radio frequencies.

PMID- 16090661
TI  - Characteristic periodic motion of polymers in shear flow.
AB  - The motion of both free and tethered polymer molecules as well as rigid Brownian
      rods in unbound shear flow is found to be characterized by a clear periodicity or
      tumbling frequency. Periodicity is shown using a combination of single molecule
      DNA experiments and computer simulations. In all cases, we develop scaling laws
      for this behavior and demonstrate that the frequency of characteristic periodic
      motion scales sublinearly with flow rate.

PMID- 16090662
TI  - Diffusion processes on power-law small-world networks.
AB  - We consider diffusion processes on power-law small-world networks in different
      dimensions. In one dimension, we find a rich phase diagram, with different
      transient and recurrent phases, including a critical line with continuously
      varying exponents. The results were obtained using self-consistent perturbation
      theory and can also be understood in terms of a scaling theory, which provides a
      general framework for understanding processes on small-world networks with
      different distributions of long-range links.

PMID- 16090663
TI  - Comment on "model for heat conduction in nanofluids".

PMID- 16090665
TI  - Matter-wave localization in disordered cold atom lattices.
AB  - We propose to observe Anderson localization of ultracold atoms in the presence of
      a random potential made of atoms of another species or spin state and trapped at
      the nodes of an optical lattice, with a filling factor less than unity. Such
      systems enable a nearly perfect experimental control of the disorder, while the
      possibility of modeling the scattering potentials by a set of pointlike ones
      allows an exact theoretical analysis. This is illustrated by a detailed analysis
      of the one-dimensional case.

PMID- 16090666
TI  - Superfluid-insulator transition in a moving system of interacting bosons.
AB  - We analyze the stability of superfluid currents in a system of strongly
      interacting ultracold atoms in an optical lattice. We show that such a system
      undergoes a dynamic, irreversible phase transition at a critical phase gradient
      that depends on the interaction strength between atoms. At commensurate filling,
      the phase boundary continuously interpolates between the classical modulation
      instability of a weakly interacting condensate and the equilibrium quantum phase
      transition into a Mott insulator state at which the critical current vanishes. We
      argue that quantum fluctuations smear the transition boundary in low dimensional
      systems. Finally we discuss the implications to realistic experiments.

PMID- 16090667
TI  - Experimental violation of a cluster state bell inequality.
AB  - Cluster states are a new type of multiqubit entangled states with entanglement
      properties exceptionally well suited for quantum computation. In the present
      work, we experimentally demonstrate that correlations in a four-qubit linear
      cluster state cannot be described by local realism. This exploration is based on
      a recently derived Bell-type inequality [V. Scarani et al., Phys. Rev. A 71,
      042325 (2005)] which is tailored, by using a combination of three- and four
      particle correlations, to be maximally violated by cluster states but not
      violated at all by GHZ states. We observe a cluster-state Bell parameter of
      2.59+/-0.08, which is more than 7sigma larger than the threshold of 2 imposed by
      local realism.

PMID- 16090668
TI  - Molecular probe of pairing in the BEC-BCS crossover.
AB  - We have used optical molecular spectroscopy to probe the many-body state of
      paired 6Li atoms near a broad Feshbach resonance. The optical probe projects
      pairs of atoms onto a vibrational level of an excited molecule. The rate of
      excitation enables a precise measurement of the closed-channel contribution to
      the paired state. This contribution is found to be quite small, supporting the
      concept of universality for the description of broad Feshbach resonances. The
      dynamics of the excitation provide clear evidence for pairing across the BEC-BCS
      crossover and into the weakly interacting BCS regime.

PMID- 16090669
TI  - Realization of a decoherence-free subspace using multiple quantum coherences.
AB  - This Letter presents a two-dimensional nuclear magnetic resonance (NMR) approach
      for constructing a two-logical-qubit decoherence-free subspace (DFS) by using
      four multiple-quantum coherences of a CH3 spin system as logical qubits. The
      three protons in this spin system are magnetically equivalent and can only be
      used as a single qubit in one-dimensional NMR. We have experimentally
      demonstrated that our DFS can protect against more types of decoherences than
      those of the one composed of four noisy physical qubits all with different
      chemical shifts. This idea may provide new insights into extending qubit systems
      in the sense that it effectively utilizes the magnetically equivalent nuclei.

PMID- 16090670
TI  - A class of time-machine solutions with a compact vacuum core.
AB  - We present a class of curved-spacetime vacuum solutions which develop closed
      timelike curves at some particular moment. We then use these vacuum solutions to
      construct a time-machine model. The causality violation occurs inside an empty
      torus, which constitutes the time-machine core. The matter field surrounding this
      empty torus satisfies the weak, dominant, and strong energy conditions. The model
      is regular, asymptotically flat, and topologically trivial. Stability remains the
      main open question.

PMID- 16090671
TI  - (2+1)-dimensional charged black hole in topologically massive electrodynamics.
AB  - The 2+1 black hole coupled to a Maxwell field can be charged in two different
      ways. Besides a Coulomb field, whose potential grows logarithmically in the
      radial coordinate, there also exists a topological charge due to the existence of
      a noncontractible cycle. The topological charge does not gravitate and is somehow
      decoupled from the black hole. This situation changes if one turns on the Chern
      Simons term for the Maxwell field. First, the flux integral at infinity becomes
      equal to the topological charge. Second, demanding regularity of the black hole
      horizon, the Coulomb charge must vanish identically. Hence, in 2+1 topologically
      massive electrodynamics coupled to gravity, the black hole can support holonomies
      only for the Maxwell field. This means that the charged black hole is constructed
      from the vacuum by means of spacetime identifications.

PMID- 16090672
TI  - General N=1 supersymmetric flux vacua of massive type IIA string theory.
AB  - We derive conditions for the existence of four-dimensional N=1 supersymmetric
      flux vacua of massive type IIA string theory with general supergravity fluxes
      turned on. For an SU(3) singlet Killing spinor, we show that such flux vacua
      exist when the internal geometry is nearly Kahler. The geometry is not warped,
      all the allowed fluxes are proportional to the mass parameter, and the dilaton is
      fixed by a ratio of (quantized) fluxes. The four-dimensional cosmological
      constant, while negative, becomes small in the vacuum with the weak string
      coupling.

PMID- 16090674
TI  - Radiatively generated isospin violations in the nucleon and the NuTeV anomaly.
AB  - Predictions of isospin asymmetries of valence and sea distributions are presented
      which are generated by QED leading Oalpha photon bremsstrahlung effects. Together
      with isospin violations arising from nonperturbative hadronic sources (such as
      quark and target mass differences) as well as with even a conservative
      contribution from a strangeness asymmetry (s not equal to s), the discrepancy
      between the large NuTeV anomaly result for sin(2Theta(w)) and the world average
      of other measurements is removed.

PMID- 16090676
TI  - Production of multiply heavy flavored baryons from quark gluon plasma in
      relativistic heavy ion collisions.
AB  - It is argued that in heavy ion collisions at the CERN Large Hadron Collider (LHC)
      there could be a sizable production of baryons containing two or three heavy
      quarks from statistical coalescence. This production mechanism is peculiar of
      quark gluon plasma, and the predicted rates, in heavy ion collisions at LHC
      energies, exceed those from a purely hadronic scenario, particularly for Xi(bc)
      and Omega(ccc). Thus, in addition to the interest in the discovery of these new
      states, enhanced ratios of these baryons over singly heavy flavored hadrons, like
      B or D, in heavy ion collisions with respect to pp at the same energy, would be a
      clear indication of kinetic equilibration of heavy quarks in the quark gluon
      plasma.

PMID- 16090677
TI  - Effective nucleon masses in symmetric and asymmetric nuclear matter.
AB  - The momentum and isospin dependence of the in-medium nucleon mass are studied.
      Two definitions of the effective mass, i.e., the Dirac mass m*D and the
      nonrelativistic mass m*NR which parametrizes the energy spectrum, are compared.
      Both masses are determined from relativistic Dirac-Brueckner-Hartree-Fock
      calculations. The nonrelativistic mass shows a distinct peak around the Fermi
      momentum. The proton-neutron mass splitting in isospin asymmetric matter is
      m*D,n<m*D,p and opposite for the nonrelativistic mass, i.e., m*NR,n>m*NR,p, which
      is consistent with nonrelativistic approaches.

PMID- 16090678
TI  - Observation of proton radioactivity of the (21+) high-spin isomer in 94Ag.
AB  - We have observed direct one-proton decay of the (21+) isomer in the N=Z nuclide
      94Ag into high-spin states in 93Pd by detecting protons in coincidence with gamma
      gamma correlations and applying gamma gates based on known 93Pd levels. Two decay
      branches have been identified, with proton energies of 0.79(3) and 1.01(3) MeV
      and branching ratios of 1.9(5)% and 2.2(4)%, respectively. The corresponding
      partial half-life values are 21(6) and 18(4) s. The Q value of the direct proton
      decay of the (21+) isomer was found to be 5.78(3) MeV. The very small reduced
      widths of the observed proton decays might reflect dominating collective
      configurations in the (21+) isomer, and the fine structure of the proton spectrum
      might indicate a strong deformation of this state.

PMID- 16090679
TI  - Quadrupole deformation of the self-conjugate nucleus 72Kr.
AB  - We report on the first determination of the absolute B(E2;0+(1)-->2+(1))
      excitation strength in the N=Z nucleus 72Kr. 72Kr is the heaviest N=Z nucleus for
      which this quantity has been measured and provides a benchmark in a region of the
      nuclear chart dominated by rapidly changing deformations and shapes mediated by
      the interplay of strongly oblate and prolate-driving orbitals. The deduced
      quadrupole deformation strength is in agreement with a variety of self-consistent
      models that predict an oblate shape for the ground state of 72Kr. Large-scale
      shell-model Monte Carlo calculations reproduce the experimental B(E2) value and
      link the result to the occupation of the deformation-driving g9/2 orbit.

PMID- 16090680
TI  - Direct frequency comb measurements of absolute optical frequencies and population
      transfer dynamics.
AB  - A phase-stabilized femtosecond laser comb is directly used for high-resolution
      spectroscopy and absolute optical frequency measurements of one- and two-photon
      transitions in laser-cooled 87Rb atoms. Absolute atomic transition frequencies,
      such as the 5S1/2 F=2-->7S1/2 F"=2 two-photon resonance measured at 788,794
      768,921 (44) kHz, are determined without a priori knowledge about their values.
      Detailed dynamics of population transfer driven by a sequence of pulses are
      uncovered and taken into account for the measurement of the 5P states via
      resonantly enhanced two-photon transitions.

PMID- 16090681
TI  - Ultrasoft x-ray Bremsstrahlung isochromatic spectra from 300-2000 eV electrons on
      Ar and Kr.
AB  - For the first time the bremsstrahlung effect was studied experimentally in the
      spectral region of 6.5-10 nm with 300-2000 eV electron scattering on Ar and Kr
      atoms. The isochromatic curves displayed maxima at electron energies of
      approximately = 0.7 keV (Ar) and approximately =1 keV (Kr); their positions are
      almost independent of the radiation wavelength in the range studied. These
      experimental data cannot be treated in the framework of theory based on the first
      Born approximation. A phenomenological modification of the quasiclassical (soft
      photon) approximation is proposed which gives a qualitative treatment of data.

PMID- 16090682
TI  - Resonant light scattering by optical solitons.
AB  - We consider the process of light scattering by optical solitons in a planar
      waveguide with homogeneous and inhomogeneous refractive index cores. We observe
      resonant reflection (Fano resonances) as well as resonant transmission of light
      by optical solitons. All resonant effects can be controlled in experiment by
      changing the soliton intensity.

PMID- 16090683
TI  - Stable spatiotemporal solitons in bessel optical lattices.
AB  - We investigate the existence and stability of three-dimensional solitons
      supported by cylindrical Bessel lattices in self-focusing media. If the lattice
      strength exceeds a threshold value, we show numerically, and using the
      variational approximation, that the solitons are stable within one or two
      intervals of values of their norm. In the latter case, the Hamiltonian versus
      norm diagram has a swallowtail shape with three cuspidal points. The model
      applies to Bose-Einstein condensates and to optical media with saturable
      nonlinearity, suggesting new ways of making stable three-dimensional solitons and
      "light bullets" of an arbitrary size.

PMID- 16090684
TI  - Soliton as strange attractor: nonlinear synchronization and chaos.
AB  - We show that dissipative solitons can have dynamics similar to that of a strange
      attractor in low-dimensional systems. Using a model of a passively mode-locked
      fiber laser as an example, we show that soliton pulsations with periods equal to
      several round-trips of the cavity can be chaotic, even though they are
      synchronized with the round-trip time. The chaotic part of this motion is
      quantified using a two-dimensional map and estimating the Lyapunov exponent. We
      found a specific route to chaotic motion that occurs through the creation,
      increase, and overlap of "islands" of chaos rather than through multiplication of
      frequencies.

PMID- 16090685
TI  - Subcritical finite-amplitude solutions for plane Couette flow of viscoelastic
      fluids.
AB  - Plane Couette flow of viscoelastic fluids is shown to exhibit a purely elastic
      subcritical instability at a very small-Reynolds number in spite of being
      linearly stable. The mechanism of this instability is proposed and the nonlinear
      stability analysis of plane Couette flow of the Upper-Convected Maxwell fluid is
      presented. Above a critical Weissenberg number, a small finite-size perturbation
      is sufficient to create a secondary flow, and the threshold value for the
      amplitude of the perturbation decreases as the Weissenberg number increases. The
      results suggest a scenario for weakly turbulent viscoelastic flow which is
      similar to the one for Newtonian fluids as a function of Reynolds number.

PMID- 16090686
TI  - Flow reversal in a simple dynamical model of turbulence.
AB  - In this Letter, we study a simple hydrodynamical model showing abrupt flow
      reversals at random times. For a suitable range of parameters, we show that the
      dynamics of flow reversal is accurately described by stochastic differential
      equations, where the noise represents the effect of turbulence.

PMID- 16090687
TI  - Scaling properties in the production range of shear dominated flows.
AB  - In large Reynolds number turbulence, isotropy is recovered as the scale is
      reduced and homogeneous-isotropic scalings are eventually observed. This picture
      is violated in many cases, e.g., wall bounded flows, where, due to the shear,
      different scaling laws emerge. This effect has been ascribed to the contamination
      of the inertial range by the larger anisotropic scales. The issue is addressed
      here by analyzing both numerical and experimental data for a homogeneous shear
      flow. In fact, under strong shear, the alteration of the scaling exponents is not
      induced by the contamination from the anisotropic sectors. Actually, the
      exponents are universal properties of the isotropic component of the structure
      functions of shear dominated flows. The implications are discussed in the context
      of turbulence near solid walls, where improved closure models would be advisable.

PMID- 16090673
TI  - Search for anomalous kinematics in tt dilepton events at CDF II.
AB  - We report on a search for anomalous kinematics of tt dilepton events in pp
      collisions at square root of s=1.96 TeV using 193 pb(-1) of data collected with
      the CDF II detector. We developed a new a priori technique designed to isolate
      the subset in a data sample revealing the largest deviation from standard model
      (SM) expectations and to quantify the significance of this departure. In the four
      variable space considered, no particular subset shows a significant discrepancy,
      and we find that the probability of obtaining a data sample less consistent with
      the SM than what is observed is 1.0%-4.5%.

PMID- 16090688
TI  - Transport mechanisms of falling crystals detached from the freezing front during
      solidification of a hypereutectic binary mixture.
AB  - Experiments studying transport phenomena during directional solidification of a
      hypereutectic binary solution in a top-cooled rectangular cavity are often
      characterized by the descendence of fragmented solid crystals through the
      unfrozen fluid. This observation, however, is yet to be fundamentally explained
      from a theoretical perspective. In this Letter, we propose a new model to
      describe stochastic dynamics of the falling crystals, which is not only
      applicable to this specific situation, but also appropriate for a generalized
      mathematical description of evolution of solid particles in the presence of
      stochastic fluctuations from the ambience accompanied by the growth or
      dissolution of crystals. Simulations of the proposed model also show an extremely
      good agreement between the theoretical predictions and earlier experimental
      findings.

PMID- 16090689
TI  - Buoyant plumes and vortex rings in an autocatalytic chemical reaction.
AB  - Buoyant plumes, evolving free of boundary constraints, may develop well-defined
      mushroom-shaped heads. In conventional plumes, overturning flow in the head
      entrains less buoyant fluid from the surroundings as the head rises, robbing the
      plume of its driving force. We consider here a new type of plume in which the
      source of buoyancy is an autocatalytic chemical reaction. The reaction occurs at
      a sharp front which separates reactants from less dense products. In this type of
      autocatalytic plume, entrainment assists the reaction, producing new buoyancy
      which fuels an accelerating plume head. When the head has grown to a critical
      size, it detaches from the upwelling conduit, forming an accelerating, buoyant
      vortex ring. A second-generation head then develops at the point of detachment.
      Multiple generations of autocatalytic vortex rings can detach from a single
      triggering event.

PMID- 16090690
TI  - Probing hot and dense laser-induced plasmas with ultrafast XUV pulses.
AB  - In this Letter, we demonstrate the instantaneous creation of a hot solid-density
      plasma generated by focusing an intense femtosecond, high temporal contrast laser
      on an ultrathin foil (100 nm) in the 10(18) W/cm2 intensity range. The use of
      high-order harmonics generated in a gas jet, providing a probe beam of
      sufficiently short wavelengths to penetrate such a medium, enables the study of
      the dynamics of this plasma on the 100 fs time scale. The comparison of the
      transmission of two successive harmonics permits us to determine the electronic
      density and the temperature with accuracies better than 15%, never achieved up to
      this date in the regime of laser pulses at relativistic intensity.

PMID- 16090691
TI  - New source of dense, cryogenic positron plasmas.
AB  - We have developed a new method, based on the ballistic transfer of preaccumulated
      plasmas, to obtain large and dense positron plasmas in a cryogenic environment.
      The method involves transferring plasmas emanating from a region with a low
      magnetic field (0.14 T) and relatively high pressure (10(-9) mbar) into a 15 K
      Penning-Malmberg trap immersed in a 3 T magnetic field with a base pressure
      better than 10(-13) mbar. The achieved positron accumulation rate in the high
      field cryogenic trap is more than one and a half orders of magnitude higher than
      the previous most efficient UHV compatible scheme. Subsequent stacking resulted
      in a plasma containing more than 1.2 x 10(9) positrons, which is a factor 4
      higher than previously reported. Using a rotating wall electric field, plasmas
      containing about 20 x 10(6) positrons were compressed to a density of 2.6 x
      10(10) cm(-3). This is a factor of 6 improvement over earlier measurements.

PMID- 16090692
TI  - Heat transfer in a two-dimensional crystalline complex (dusty) plasma.
AB  - Heating and heat transfer were studied in a two-dimensional crystalline complex
      plasma at the kinetic level. The lattice was formed of microspheres levitated in
      a plasma sheath. One half of the crystal was heated anisotropically to obtain
      higher kinetic temperatures in one direction and heat conduction was observed in
      real time. It was found that the longitudinal phonons conduct heat better than
      the transverse. The thermometric conductivity coefficient was measured to be 53
      mm2/s for longitudinal heating and 30 mm2/s for transverse heating. Heat decay
      lengths and energy exchange times between the temperature components were
      determined.

PMID- 16090693
TI  - Observations of ion-beam formation in a current-free double layer.
AB  - With nonperturbative laser-induced fluorescence measurements of ion flow, we
      confirm numerical simulations of spontaneous electric double-layer (DL) formation
      in a current-free expanding plasma. Measurements in two different experiments
      confirm that the DL is localized to the region of rapidly diverging magnetic
      field. The measurements indicate that the trapped ion population is a single
      Maxwellian, that the spatial gradient of the energy of ions accelerated through
      the DL matches the magnetic field gradient, and that DL formation is triggered
      when the ion-neutral collisional mean-free path exceeds the magnetic field
      gradient scale length.

PMID- 16090694
TI  - Laser-pulse-induced second-harmonic and hard x-ray emission: role of plasma-wave
      breaking.
AB  - We report time resolved measurements of second-harmonic and hard x rays emitted
      during the interaction of an intense laser pulse (10(16) W cm(-2), 100 fs) with a
      preplasma generated on a solid target. We observe that for a particular length
      scale the second harmonic goes through a minimum, while hard x-ray emission on
      the contrary maximizes. Theoretical or numerical modeling of this anticorrelation
      in terms of wave breaking of strongly driven electron plasma waves clearly brings
      out hitherto unexplored links between the physical mechanisms of second-harmonic
      generation and hard x-ray emission.

PMID- 16090695
TI  - Effect of strain on the appearance of subcritical nuclei of ge nanohuts on
      Si(001).
AB  - Real-time scanning tunneling microscopy observations of nucleation and
      heteroepitaxial growth of Ge nanocrystals (from germane) on Si(001) indicate that
      in the absence of Si-Ge intermixing the formation of full hut cluster islands is
      preceded by the nucleation of "subcritical" nuclei consisting of two adjacent
      truncated tetrahedral pyramids, which, upon unification, form a tiny square-based
      pyramidal "critical nucleus" It is suggested that such a precursor aids in
      surpassing the nucleation barrier and that the recently reported gradual faceting
      of prepyramids is characteristic of only Ge(Si) alloys.

PMID- 16090696
TI  - Cracks in thin sheets: when geometry rules the fracture path.
AB  - We study the propagation of brittle fractures coupled to large out-of-plane
      bending, as when a brittle elastic thin sheet is cut by a moving object. Taking
      into account the separation of the film's bending and stretching energies and
      using fracture theory we show that such cracks propagate according to a simple
      set of geometrical rules in the limit of small thickness. In particular, this
      provides some insight into the geometrical origin of the oscillatory fracture
      patterns reported in two recent experiments. Numerical integration of our
      geometrical rules accurately reproduces both the shape of the fracture pattern
      and the detailed time evolution of the propagation of the crack tip, for various
      geometries of the cutting object.

PMID- 16090675
TI  - Measurement of the cross section for prompt diphoton production in pp collisions
      at square root of s=1.96 TeV.
AB  - We report a measurement of the rate of prompt diphoton production in pp
      collisions at square root of s=1.96 TeV using a data sample of 207 pb(-1)
      collected with the upgraded Collider Detector at Fermilab. The background from
      nonprompt sources is determined using a statistical method based on differences
      in the electromagnetic showers. The cross section is measured as a function of
      the diphoton mass, the transverse momentum of the diphoton system, and the
      azimuthal angle between the two photons and is found to be consistent with
      perturbative QCD predictions.

PMID- 16090697
TI  - General rules for predicting phase transitions in perovskites due to octahedral
      tilting.
AB  - Recent experiments on several oxide perovskites reveal that they undergo tilt
      phase transitions to higher-symmetry phases on increasing pressure and that
      dTc/dP<0, contrary to a general rule previously proposed for such zone-boundary
      transitions. We show that the negative slope of the phase boundary is a
      consequence of the octahedra in these perovskites being more compressible than
      the extra-framework cation sites. Conversely, when the octahedra are stiffer than
      the extra-framework cation sites, the phase transition temperatures increase with
      increasing pressure, dTc/dP>0.

PMID- 16090698
TI  - Probing slow dynamics in supported thin polymer films.
AB  - We have used variable cooling rate ellipsometric measurements to probe the slow
      dynamics in thin supported polystyrene films. For the slowest cooling rates
      (approximately 1 K/min) the measured Tg values are reduced below the bulk value
      with the measured Tg of 341 K for a 6 nm film. As the cooling rate is increased
      the Tg reductions become smaller until at cooling rates >90 K/min there is only
      slight evidence for a film-thickness-dependent Tg value. By relating the cooling
      rate to a relaxation time, we show that the relaxation dynamics of the thin films
      appears to become Arrhenius with an activation energy that decreases with
      decreasing film thickness. We discuss this in terms of a possible connection to a
      length scale for cooperative motion. Finally, the results can be used to resolve
      a number of outstanding contradictory reports in the literature.

PMID- 16090699
TI  - Two-dimensional melting transition observed in a block copolymer.
AB  - We report the observation of two-dimensional melting in a monolayer film of a
      sphere-forming diblock copolymer. By annealing in a well-controlled temperature
      gradient we obtain a complete record of the transition from a low-temperature
      hexatic phase to a high-temperature liquid in a single experiment. We investigate
      the temperature dependence of the orientational and translational correlation
      lengths, as well as of the topological defect density. All evidence suggests that
      the melting transition is first-order, but correlations in the liquid phase
      indicate the existence of an underlying second-order transition preempted by the
      first-order freezing.

PMID- 16090700
TI  - Ab initio identification of the nitrogen diffusion mechanism in silicon.
AB  - In this Letter, we present ab initio results identifying a new diffusion path for
      the nitrogen pair complex in silicon, resulting in an effective diffusivity of
      67exp((-2.38 eV/kT) cm2/s. This nudged elastic band result is compared with other
      nitrogen diffusion paths and mechanisms, and is determined to have unmatched
      agreement with experimental results. It is also shown that careful consideration
      of total energy corrections and use of a fully temperature-dependent diffusion
      prefactor have modest but important effects on the calculation of diffusivity for
      paired and for interstitial nitrogen.

PMID- 16090701
TI  - Adhesion of polymer vesicles.
AB  - The adhesion and bending modulus of polybutadiene-poly(ethylene oxide) block
      copolymer vesicles made from a bidisperse mixture of polymers is measured using
      micropipette aspiration. The adhesion energy between biotinylated vesicles and
      avidin beads is modeled by incorporating the extension of the adhesive ligands
      above the surface brush of the vesicle according to the blob model of bidisperse
      polymer mixtures of Komura and Safran assuming the polymer brush at the surface
      of the vesicle is compact. The same model accurately reproduces the scaling of
      the bending modulus with polymer composition.

PMID- 16090702
TI  - Incommensurability of a confined system under shear.
AB  - We study a chain of harmonically interacting atoms confined between two
      sinusoidal substrate potentials, when the top substrate is driven through an
      attached spring with a constant velocity. This system is characterized by three
      inherent length scales and closely related to physical situations with confined
      lubricant films. We show that, contrary to the standard Frenkel-Kontorova model,
      the most favorable sliding regime is achieved by choosing chain-substrate
      incommensurabilities belonging to the class of cubic irrational numbers (e.g.,
      the spiral mean). At large chain stiffness, the well known golden mean
      incommensurability reveals a very regular time-periodic dynamics with always
      higher kinetic friction values with respect to the spiral mean case.

PMID- 16090703
TI  - Kinetic evolution and equilibrium morphology of strained islands.
AB  - Self-assembled SiGe islands grown on Si(001) leave behind characteristic
      "footprints" that reveal that small islands shrink, losing material to nearby
      larger islands. The critical size, dividing shrinking from growing islands,
      corresponds to the pyramid-to-dome shape transition, consistent with "anomalous
      coarsening" While shrinking, {105}-faceted pyramids transform into truncated
      pyramids and ultimately into unfaceted mounds. The similarity to behavior during
      island growth indicates that island shape and facet formation are
      thermodynamically determined.

PMID- 16090704
TI  - Ferro-type orbital state in the Mott transition system Ca2-xSrxRuO4 studied by
      the resonant x-ray scattering interference technique.
AB  - We have succeeded in detecting ferro-type orbital states in Ca2-xSrxRuO4, which
      is the first outcome in a 4d Mott transition system by the resonant x-ray
      scattering interference technique. For x=0 (Mott insulator), the resonant signal
      for d(xy) orbital ordering is observed even at room temperature, in which the
      Jahn-Teller distortion is negligible. The signal disappears near the metal
      insulator transition. On the other hand, in a metallic phase for x=0.5, orbital
      polarization with d(yz/zx) character dominates. With lowering temperature, the
      magnitude of the resonant signal slightly decreases owing to the additional
      influence of the gamma band with d(xy) character.

PMID- 16090705
TI  - Thermodynamics of a Fermi liquid beyond the low-energy limit.
AB  - We consider the nonanalytic temperature dependences of the specific heat
      coefficient, C(T)/T, and spin susceptibility, chi(s)(T), of 2D interacting
      fermions beyond the weak-coupling limit. We demonstrate within the Luttinger-Ward
      formalism that the leading temperature dependences of C(T)/T and chi(s)(T) are
      linear in T, and are described by the Fermi liquid theory. We show that these
      temperature dependences are universally determined by the states near the Fermi
      level and, for a generic interaction, are expressed via the spin and charge
      components of the exact backscattering amplitude of quasiparticles. We compare
      our theory to recent experiments on monolayers of He3.

PMID- 16090706
TI  - Quantum critical 5f electrons avoid singularities in U(Ru,Rh)2Si2.
AB  - We present specific heat measurements of 4% Rh-doped URu2Si2 at magnetic fields
      around the proposed metamagnetic transition field H(m) approximately 34 T,
      revealing striking similarities to the isotructural Ce analog CeRu2Si2 for
      H>H(m). This suggests that strongly renormalized hybridized-band models apply
      equally well to both systems. The vanishing bandwidths as H-->H(m) are consistent
      with a quantum-critical point close to H(m). The existence of a phase transition
      into an ordered phase in the vicinity of H(m) for 4% Rh-doped URu2Si2, but not
      for CeRu2Si2, is consistent with a stronger superexchange in the case of the U 5f
      system. Irreversible processes at the transition indicate a strong coupling of
      the 5f orbitals to the lattice, most suggestive of electric quadrupolar order.

PMID- 16090707
TI  - Direct observation of domain-wall configurations transformed by spin currents.
AB  - Direct observations of current-induced domain-wall propagation by spin-polarized
      scanning electron microscopy are reported. Current pulses move head-to-head as
      well as tail-to-tail walls in submicrometer Fe20Ni80 wires in the direction of
      the electron flow, and a decay of the wall velocity with the number of injected
      current pulses is observed. High-resolution images of the domain walls reveal
      that the wall spin structure is transformed from a vortex to a transverse
      configuration with subsequent pulse injections. The change in spin structure is
      directly correlated with the decay of the velocity.

PMID- 16090708
TI  - Sample-specific and ensemble-averaged magnetoconductance of individual single
      wall carbon nanotubes.
AB  - We discuss magnetotransport measurements on individual single-wall carbon
      nanotubes (SWNTs) with low contact resistance, performed as a function of
      temperature and gate voltage. We find that the application of a magnetic field
      perpendicular to the tube axis results in a large magnetoconductance of the order
      of e2/h at low temperature. We demonstrate that this magnetoconductance consists
      of a sample-specific and of an ensemble-averaged contribution, both of which
      decrease with increasing temperature. The observed behavior resembles very
      closely the behavior of more conventional multichannel mesoscopic wires,
      exhibiting universal conductance fluctuations and weak localization. A
      theoretical analysis of our experiments will enable us to reach a deeper
      understanding of phase-coherent one-dimensional electronic motion in SWNTs.

PMID- 16090709
TI  - Theoretical evidence for equivalence between the ground states of the strong
      coupling BCS Hamiltonian and the antiferromagnetic Heisenberg model.
AB  - By explicitly computing wave function overlap via exact diagonalization in finite
      systems, we provide evidence indicating that, in the limit of strong coupling,
      i.e., Delta/t--> infinity the ground state of the Gutzwiller-projected BCS
      Hamiltonian (accompanied by proper particle-number projection) is identical to
      the exact ground state of the 2D antiferromagnetic Heisenberg model on the square
      lattice. This identity is adiabatically connected to a very high overlap between
      the ground states of the projected BCS Hamiltonian and the t-J model at moderate
      doping.

PMID- 16090710
TI  - Experimental observation of bias-dependent nonlocal Andreev reflection.
AB  - We investigate transport through hybrid structures consisting of two normal metal
      leads connected via tunnel barriers to one common superconducting electrode. We
      find clear evidence for the occurrence of nonlocal Andreev reflection and elastic
      cotunneling through a superconductor when the separation of the tunnel barrier is
      comparable to the superconducting coherence length. The probability of the two
      processes is energy dependent, with elastic cotunneling dominating at low energy
      and nonlocal Andreev reflection at higher energies. The energy scale of the
      crossover is found to be the Thouless energy of the superconductor, which
      indicates the phase coherence of the processes. Our results are relevant for the
      realization of recently proposed entangler devices.

PMID- 16090711
TI  - Frozen low-spin interface in ultrathin Fe films on Cu(111).
AB  - In ultrathin film systems, it is a major challenge to understand how a thickness
      driven phase transition proceeds along the cross-sectional direction of the
      films. We use ultrathin Fe films on Cu(111) as a prototype system to demonstrate
      how to obtain such information using an in situ scanning tunneling microscope and
      the surface magneto-optical Kerr effect. The magnetization depth profile of a
      thickness-driven low-spin to high-spin magnetic phase transition is deduced from
      the experimental data, which leads us to conclude that a low-spin Fe layer at the
      Fe/Cu interface stays live upon the phase transition. The magnetically live low
      spin phase is believed to be induced by a frozen fcc Fe layer that survives a
      thickness-driven fcc-->bcc structural transition.

PMID- 16090712
TI  - Backflow-induced asymmetric collapse of disclination lines in liquid crystals.
AB  - We present experiments where opposed pairs of planar parallel disclination lines
      of topological strength s=+/-1 move due to their mutual attraction. Our
      measurements show that their motion is clearly asymmetric, with +1 defects moving
      up to twice as fast as -1 ones. This is a clear indication of backflow, given the
      intrinsic isotropic elasticity of our system. A phenomenological model is able to
      account for the experimental observations by renormalizing the orientational
      diffusivity estimated from the velocity of each defect.

PMID- 16090713
TI  - Light-induced layer by layer thickening in photosensitive liquid crystal
      membranes.
AB  - Photosensitive smectic membranes of pure liquid crystal (LC) were studied under
      white light illumination. A thickness increase is observed in the illuminated
      film area. Appropriate light and thermal conditions lead to a thickening layer by
      layer process. This unusual phenomenon is opposite to the well-known step-by-step
      thinning transitions under heating. We give a phenomenological interpretation for
      thickening based on layer transport of LC matter towards the illuminated area.

PMID- 16090714
TI  - A horizontal Brazil-nut effect and its reverse.
AB  - Transport effects in a monolayer consisting of a binary granular mixture,
      confined in a horizontally vibrating circular dish, are studied experimentally
      and compared with a reduced theoretical model. Depending on the ratio of the
      particles' material density and size, migration of the larger particles occurs
      either towards the boundary or to the center of the circular container. These
      directed motions show similarities to the Brazil-nut effect and its reverse form.

PMID- 16090715
TI  - Experimental study of granular compaction dynamics at different scales: grain
      mobility, hexagonal domains, and packing fraction.
AB  - We present an original experimental study of the compaction dynamics for two
      dimensional granular systems. Compaction dynamics is measured at three different
      scales: the macroscopic scale through the normalized packing fraction rho, the
      mesoscopic scale through the normalized fraction phi of hexagonal domains in the
      system, and the microscopic scale through the grain mobility mu. Moreover, the
      hexagonal domains are found to obey a growth process dominated by the
      displacement of domain boundaries. A global picture of compaction dynamics
      relevant at each scale is proposed.

PMID- 16090716
TI  - Renormalization-group transformations and correlations of seismicity.
AB  - The effect of transformations analogous to those of the real-space
      renormalization group are analyzed for the temporal occurrence of earthquakes. A
      recently reported scaling law for the distribution of recurrence times implies
      that these distributions must be invariant under such transformations, for which
      the role of the correlations between the magnitudes and the recurrence times are
      fundamental. This approach puts the study of the temporal structure of seismicity
      in the context of critical phenomena.

PMID- 16090717
TI  - Comment on "molecular chemisorption as the theoretically preferred pathway for
      water adsorption on ideal rutile TiO2(110)".

PMID- 16090719
TI  - Phase coherence length and quantum interference patterns at step edges.

PMID- 16090721
TI  - Realization of Hardy's thought experiment with photons.
AB  - We present an experimental realization of Hardy's thought experiment [Phys. Rev.
      Lett. 68, 2981 (1992)], using photons. The experiment consists of a pair of Mach
      Zehnder interferometers that interact through photon bunching at a beam splitter.
      A striking contradiction is created between the predictions of quantum mechanics
      and local hidden variables. The contradiction relies on nonmaximally entangled
      position states of two particles. A Clauser-Horne-type inequality is derived and
      violated.

PMID- 16090722
TI  - Quantum state reconstruction via continuous measurement.
AB  - We present a new procedure for quantum state reconstruction based on weak
      continuous measurement of an ensemble average. By applying controlled evolution
      to the initial state, new information is continually mapped onto the measured
      observable. A Bayesian filter is then used to update the state estimate in
      accordance with the measurement record. This generalizes the standard paradigm
      for quantum tomography based on strong, destructive measurements on separate
      ensembles. This approach to state estimation induces minimal perturbation of the
      measured system, giving information about observables whose evolution cannot be
      described classically in real time and opening the door to new types of quantum
      feedback control.

PMID- 16090723
TI  - Hyperfine coherence in the presence of spontaneous photon scattering.
AB  - The coherence of a hyperfine-state superposition of a trapped 9Be+ ion in the
      presence of off-resonant light is studied experimentally. It is shown that
      Rayleigh elastic scattering of photons that does not change state populations
      also does not affect coherence. We observe coherence times that exceed the
      average scattering time of 19 photons which is determined from measured Stark
      shifts. This result implies that, with sufficient control over its parameters,
      laser light can be used to manipulate hyperfine-state superpositions with very
      little decoherence.

PMID- 16090724
TI  - Equation of state and collective frequencies of a trapped Fermi gas along the BEC
      unitarity crossover.
AB  - We show that the study of the collective oscillations in a harmonic trap provides
      a very sensitive test of the equation of state of a Fermi gas near a Feshbach
      resonance. Using a scaling approach, whose high accuracy is proven by comparison
      with exact hydrodynamic solutions, the frequencies of the lowest compressional
      modes are calculated at T=0 in terms of a dimensionless parameter characterizing
      the equation of state. The predictions for the collective frequencies, obtained
      from the equations of state of mean-field BCS theory and of recent Monte Carlo
      calculations, are discussed in detail.

PMID- 16090725
TI  - Zoo of quantum phases and excitations of cold bosonic atoms in optical lattices.
AB  - Quantum phases and phase transitions of weakly to strongly interacting bosonic
      atoms in deep to shallow optical lattices are described by a single multiorbital
      mean-field approach in real space. For weakly interacting bosons in one
      dimension, the critical value of the superfluid to Mott insulator (MI) transition
      found is in excellent agreement with many-body treatments of the Bose-Hubbard
      model. For strongly interacting bosons, (i) additional MI phases appear, for
      which two (or more) atoms residing in each site undergo a Tonks-Girardeau-like
      transition and localize, and (ii) on-site excitation becomes the excitation
      lowest in energy. Experimental implications are discussed.

PMID- 16090726
TI  - Entanglement generation of nearly random operators.
AB  - We study the entanglement generation of operators whose statistical properties
      approach those of random matrices but are restricted in some way. These include
      interpolating ensemble matrices, where the interval of the independent random
      parameters are restricted, pseudorandom operators, where there are far fewer
      random parameters than required for random matrices, and quantum chaotic
      evolution. Restricting randomness in different ways allows us to probe
      connections between entanglement and randomness. We comment on which properties
      affect entanglement generation and discuss ways of efficiently producing random
      states on a quantum computer.

PMID- 16090727
TI  - Experimental realization of optimal asymmetric cloning and telecloning via
      partial teleportation.
AB  - We report an experimental realization of both optimal asymmetric cloning and
      telecloning of single photons by making use of partial teleportation of an
      unknown state. In the experiment, we demonstrate that, conditioned on the success
      of partial teleportation of single photons, not only the optimal asymmetric
      cloning can be accomplished, but also one of two outputs can be transferred to a
      distant location, realizing the telecloning. The experimental results represent a
      novel way to achieve quantum cloning and may have potential applications in the
      context of quantum communication.

PMID- 16090728
TI  - Natural multiparticle entanglement in a Fermi gas.
AB  - We investigate multipartite entanglement in a noninteracting fermion gas, as a
      function of fermion separation, starting from the many particle fermion density
      matrix. We prove that all multiparticle entanglement can be built only out of two
      fermion entanglement. Although from the Pauli exclusion principle we would always
      expect entanglement to decrease with fermion distance, we surprisingly find the
      opposite effect for certain fermion configurations. The von Neumann entropy is
      found to be proportional to the volume for a large number of particles even when
      they are arbitrarily close to each other. We will illustrate our results using
      different configurations of two, three, and four fermions at zero temperature
      although all our results can be applied to any temperature and any number of
      particles.

PMID- 16090729
TI  - Theory of control of the spin-photon interface for quantum networks.
AB  - A cavity coupling, a charged nanodot, and a fiber can act as a quantum interface,
      through which a stationary spin qubit and a flying photon qubit can be
      interconverted via a cavity-assisted Raman process. This Raman process can be
      made to generate or annihilate an arbitrarily shaped single-photon wave packet by
      pulse shaping the controlling laser field. This quantum interface forms the basis
      for many essential functions of a quantum network, including sending, receiving,
      transferring, swapping, and entangling qubits at distributed quantum nodes as
      well as a deterministic source and an efficient detector of a single-photon wave
      packet with arbitrarily specified shape and average photon number. Numerical
      study of errors from noise and system parameters on the operations shows high
      fidelity and robust tolerance.

PMID- 16090730
TI  - Repeat-until-success linear optics distributed quantum computing.
AB  - We demonstrate the possibility to perform distributed quantum computing using
      only single-photon sources (atom-cavity-like systems), linear optics, and photon
      detectors. The qubits are encoded in stable ground states of the sources. To
      implement a universal two-qubit gate, two photons should be generated
      simultaneously and pass through a linear optics network, where a measurement is
      performed on them. Gate operations can be repeated until a success is heralded
      without destroying the qubits at any stage of the operation. In contrast with
      other schemes, this does not require explicit qubit-qubit interactions, a priori
      entangled ancillas, nor the feeding of photons into photon sources.

PMID- 16090731
TI  - Dynamic decoherence control of a solid-state nuclear-quadrupole qubit.
AB  - We report on the application of a dynamic decoherence control pulse sequence on a
      nuclear-quadrupole transition in Pr3+:Y(2)SiO(5). Process tomography is used to
      analyze the effect of the pulse sequence. The pulse sequence was found to
      increase the decoherence time of the transition to over 30 seconds. Although the
      decoherence time was significantly increased, the population terms were found to
      rapidly decay on the application of the pulse sequence. The increase of this
      decay rate is attributed to inhomogeneity in the ensemble. Methods to circumvent
      this limit are discussed.

PMID- 16090732
TI  - Hydrogen burning of 17O in classical novae.
AB  - We report on the observation of a previously unknown resonance at
      E(lab)(R)=194.1+/-0.6 keV in the 17O(p,alpha)14N reaction, with a measured
      resonance strength omegagamma(palpha)=1.6 +/- 0.2 meV. We studied in the same
      experiment the 17O(p,gamma)18F reaction by an activation method and the resonance
      strength ratio was found to be omegagamma(palpha)/omegagamma(pgamma) = 470 +/-
      50. The corresponding excitation energy in the 18F compound nucleus was
      determined to be 5789.8 +/- 0.3 keV by gamma-ray measurements using the
      14N(alpha, gamma)18F reaction. These new resonance properties have important
      consequences for 17O nucleosynthesis and gamma-ray astronomy of classical novae.

PMID- 16090733
TI  - Hawking radiation in an electromagnetic waveguide?
AB  - It is demonstrated that the propagation of electromagnetic waves in an
      appropriately designed waveguide is (for large wavelengths) analogous to that
      within a curved space-time--such as around a black hole. As electromagnetic
      radiation (e.g., microwaves) can be controlled, amplified, and detected (with
      present-day technology) much easier than sound, for example, we propose a setup
      for the experimental verification of the Hawking effect. Apart from
      experimentally testing this striking prediction, this would facilitate the
      investigation of the trans-Planckian problem.

PMID- 16090734
TI  - Conserved charges and thermodynamics of the spinning Godel black hole.
AB  - We compute the mass, angular momenta, and charge of the Godel-type rotating black
      hole solution to five-dimensional minimal supergravity. A generalized Smarr
      formula is derived, and the first law of thermodynamics is verified. The
      computation rests on a new approach to conserved charges in gauge theories that
      allows for their computation at finite radius.

PMID- 16090736
TI  - Structure of the odd-A, shell-stabilized nucleus 253/102No.
AB  - In-beam gamma-ray spectroscopic measurements have been made on 253/102No. A
      single rotational band was identified up to a probable spin of 39/2planck, which
      is assigned to the 7/2(+)[624] Nilsson configuration. The bandhead energy and the
      moment of inertia provide discriminating tests of contemporary models of the
      heaviest nuclei. Novel methods were required to interpret the sparse data set
      associated with cross sections of around 50 nb. These methods included
      comparisons of experimental and simulated spectra, as well as testing for
      evidence of a rotational band in the gammagamma matrix.

PMID- 16090737
TI  - Ground state proton radioactivity from 121Pr: when was this exotic nuclear decay
      mode first discovered?
AB  - Ground-state proton radioactivity has been identified from 121Pr. A transition
      with a proton energy of E(p)=882(10) keV [Q(p)=900(10) keV] and half-life
      t(1/2)=10(+6)(-3) ms has been observed and is assigned to the decay of a highly
      prolate deformed 3/2(+) or 3/2(-) Nilsson state. The present result is found to
      be incompatible with a previously reported observation of ground-state proton
      radioactivity from 121Pr, which would have represented the discovery of this
      phenomenon.

PMID- 16090738
TI  - Electric quadrupole shift cancellation in single-ion optical frequency standards.
AB  - The electric quadrupole shift is presently the most significant source of
      uncertainty on the systematic shifts for several single-ion optical frequency
      standards. We present a simple method for cancelling this shift based on
      measurements of the Zeeman spectrum of the clock transition. This method is easy
      to implement and yields very high cancellation levels. A fractional uncertainty
      of 5 x 10(-18) for the canceled quadrupole shift is estimated for a measurement
      of the absolute frequency of the 5s (2)S(1/2)-4d (2)D(5/2) clock transition of
      88Sr+.

PMID- 16090739
TI  - Submicrometer position control of single trapped neutral atoms.
AB  - We optically detect the positions of single neutral cesium atoms stored in a
      standing wave dipole trap with a subwavelength resolution of 143 nm rms. The
      distance between two simultaneously trapped atoms is measured with an even higher
      precision of 36 nm rms. We resolve the discreteness of the interatomic distances
      due to the 532 nm spatial period of the standing wave potential and infer the
      exact number of trapping potential wells separating the atoms. Finally, combining
      an initial position detection with a controlled transport, we place single atoms
      at a predetermined position along the trap axis to within 300 nm rms.

PMID- 16090740
TI  - Quantum phases of the extended Bose-Hubbard hamiltonian: possibility of a
      supersolid state of cold atoms in optical lattices.
AB  - Cold atom optical lattices typically simulate zero-range Hubbard models. We
      discuss the theoretical possibility of using excited states of optical lattices
      to generate extended range Hubbard models. We find that bosons confined to higher
      bands of optical lattices allow for a rich phase diagram, including the
      supersolid phase. Using Gutzwiller, mean-field theory we establish the parameter
      regime necessary to maintain metastable states generated by an extended Bose
      Hubbard model.

PMID- 16090741
TI  - Triple coincidence (e,gamma2e) experiment for simultaneous electron impact
      ionization excitation of helium.
AB  - Simultaneous ionization and excitation of helium atoms by 500 eV electron impact
      is observed by a triple coincidence of an ionized slow electron, the recoiling
      He+ ion, and the radiated vacuum ultraviolet photon (lambda< or =30.4 nm).
      Kinematically complete differential cross sections are presented for the
      He+(2p)2P final ionic state, demonstrating the feasibility of a quantum
      mechanically complete experiment. The experimental data are compared to
      predictions from state-of-the-art numerical calculations. For large momentum
      transfers, a first-order treatment of the projectile-target interaction can
      reproduce the experimental angular dependence, but a second-order treatment is
      required to obtain consistent magnitudes.

PMID- 16090742
TI  - Experimental methods for detecting entanglement.
AB  - Here we present experimental realizations of two new entanglement detection
      methods: a three-measurement Bell inequality inequivalent to the Clauser-Horne
      Shimony-Holt inequality and a nonlinear Bell-type inequality based on the
      negativity measure. In addition, we provide an experimental and theoretical
      comparison between these new methods and several techniques already in use: the
      traditional Clauser-Horne-Shimony-Holt inequality, the entanglement witness, and
      complete state tomography.

PMID- 16090743
TI  - Analysis of radiation-pressure induced mechanical oscillation of an optical
      microcavity.
AB  - The theoretical work of Braginsky predicted that radiation pressure can couple
      the mechanical, mirror eigenmodes of a Fabry-Perot resonator to its optical
      modes, leading to a parametric oscillation instability. This regime is
      characterized by regenerative mechanical oscillation of the mechanical mirror
      eigenmodes. We have recently observed the excitation of mechanical modes in an
      ultrahigh Q optical microcavity. Here, we present a detailed experimental
      analysis of this effect and demonstrate that radiation pressure is the excitation
      mechanism of the observed mechanical oscillations.

PMID- 16090744
TI  - Spatiotemporal optical pulse control using microwaves.
AB  - The Davey-Stewartson system allows us to describe the interaction between a
      spatiotemporal optical pulse and adequately matched microwaves. We show that the
      interaction can lead to the formation of a two-dimensional soliton which is
      robust in the sense that it occurs in a wide range of parameters of the incident
      optical pulse and microwaves, and of the material used.

PMID- 16090745
TI  - Shock wave interaction with laser-generated single bubbles.
AB  - The interaction of a lithotripter shock wave (LSW) with laser-generated single
      vapor bubbles in water is investigated using high-speed photography and pressure
      measurement via a fiber-optic probe hydrophone. The interaction leads to
      nonspherical collapse of the bubble with secondary shock wave emission and
      microjet formation along the LSW propagation direction. The maximum pressure
      amplification is produced during the collapse phase of the bubble oscillation
      when the compressive pulse duration of the LSW matches with the forced collapse
      time of the bubble.

PMID- 16090746
TI  - High-frequency driven capillary flows speed up the gas-liquid phase transition in
      zero-gravity conditions.
AB  - Under weightlessness conditions, the phase transition of fluids is driven only by
      slow capillary flows. We investigate the effect of high-frequency vibrations to
      reproduce some features of gravity effects and show that such vibrations can
      greatly modify the phase transition kinetics. The investigation is performed in
      H2 near its critical point (critical temperature 33 K) where critical slowing
      down enables the phase transition process to be carefully studied. Gravity
      effects are compensated in a strong magnetic field gradient.

PMID- 16090747
TI  - Advection-induced spectrotemporal defects in a free-electron laser.
AB  - We evidence numerically and experimentally that advection can induce
      spectrotemporal defects in a system presenting a localized structure. Those
      defects in the spectrum are associated with the breakings induced by the drift of
      the localized solution. The results are based on simulations and experiments
      performed on the super-ACO free-electron laser. However, we show that this
      instability can be generalized using a real Ginzburg-Landau equation with (i)
      advection and (ii) a finite-size supercritical region.

PMID- 16090748
TI  - Proposal for the study of thermophysical properties of high-energy-density matter
      using current and future heavy-ion accelerator facilities at GSI Darmstadt.
AB  - The subject of high-energy-density (HED) states in matter is of considerable
      importance to numerous branches of basic as well as applied physics. Intense
      heavy-ion beams are an excellent tool to create large samples of HED matter in
      the laboratory with fairly uniform physical conditions. Gesellschaft fur
      Schwerionenforschung, Darmstadt, is a unique worldwide laboratory that has a
      heavy-ion synchrotron, SIS18, that delivers intense beams of energetic heavy
      ions. Construction of a much more powerful synchrotron, SIS100, at the future
      international facility for antiprotons and ion research (FAIR) at Darmstadt will
      lead to an increase in beam intensity by 3 orders of magnitude compared to what
      is currently available. The purpose of this Letter is to investigate with the
      help of two-dimensional numerical simulations, the potential of the FAIR to carry
      out research in the field of HED states in matter.

PMID- 16090749
TI  - Natural velocity of magnetic islands.
AB  - The phase velocity of magnetic islands is calculated in the semicollisional
      regime with cold ions. Two solution branches arise, corresponding to islands
      propagating with the ions and with the electrons. For the ion branch the phase
      velocity and the polarization current are small. For the electron branch, the
      phase velocity depends on the ratio of W, the half-width of the island, and
      rho(s), the Larmor radius calculated with the electron temperature. For W
      >>rho(s) the phase velocity is larger than the electron drift velocity and the
      polarization current is destabilizing. For W << rho(s), the situation is reversed
      provided that the density and temperature gradients point in the same direction.

PMID- 16090750
TI  - Reduced heat transport between edge-localized-mode bursts at low collisionality
      and small poloidal Larmor radius.
AB  - Nondimensional parameter dependence of heat transport between edge localized
      modes (ELMs) is examined for H mode plasmas. The electron heat diffusivity
      between ELMs is reduced to the level of ion neoclassical transport in the plasma
      edge region which is affected by ELM burst. At lower edge collisionality, the
      heat flux assigned to the heat transport between ELMs is reduced and the ELM loss
      power is enhanced. During the inter-ELM phase, the energy confinement time
      becomes larger with decreasing the edge collisionality and poloidal Larmor
      radius.

PMID- 16090752
TI  - Stabilization of interchange modes in mirror plasmas by a nonlinear rf-plasma
      wave coupling process.
AB  - Experimental and theoretical studies are made of the consequences of a nonlinear
      coupling process between pump rf waves and interchange modes in mirror plasmas.
      It is demonstrated that the interchange-stable operation window exists depending
      on the applied rf power and gamma=omega(0)/Omega(i), where omega(0) (Omega(i)) is
      the angular frequency of the applied rf wave (ion cyclotron frequency). Results
      are shown that the nonlinear wave coupling process gives rise to the operation
      window near the resonance (gamma approximately equal to 1), which is elucidated
      by theoretical analyses combined with full rf wave simulations.

PMID- 16090751
TI  - Optical deflection and temporal characterization of an ultrafast laser-produced
      electron beam.
AB  - The interaction of a laser-produced electron beam with an ultraintense laser
      pulse in free space is studied. We show that the optical pulse with a(0)=0.5
      imparts momentum to the electron beam, causing it to deflect along the laser
      propagation direction. The observed 3-degree angular deflection is found to be
      independent of polarization and in good agreement with a theoretical model for
      the interaction of free electrons with a tightly focused Gaussian pulse, but only
      when longitudinal fields are taken into account. This technique is used to
      temporally characterize a subpicosecond laser-wakefield-driven electron bunch.
      Applications to electron-beam conditioning are also discussed.

PMID- 16090753
TI  - Freezing and pressure-driven flow of solid helium in Vycor.
AB  - The recent torsional oscillator results of Kim and Chan suggest a supersolid
      phase transition in solid 4He confined in Vycor. We have used a capacitive
      technique to directly monitor density changes for helium confined in Vycor at low
      temperature and have used a piezoelectrically driven diaphragm to study the
      pressure-induced flow of solid helium into the Vycor pores. Our measurements
      showed no indication of a mass redistribution in the Vycor that could mimic
      supersolid decoupling and put an upper limit of about 0.003 microm/s on any
      pressure-induced supersolid flow in the pores of Vycor.

PMID- 16090735
TI  - Evidence for B0 s-->phiphi decay and measurements of branching ratio and A(CP)
      for B+ -->phiK+.
AB  - We present the first evidence of charmless decays of the B(0)(s) meson, the decay
      B(0)(s)--> phiphi, and a measurement of the branching ratio BR(B(0)(s)--> phiphi)
      using 180 pb(-1) of data collected by the CDF II experiment at the Fermilab
      Tevatron collider. In addition, the BR and direct CP asymmetry for the B+-->phiK+
      decay are measured. We obtain BR(B(0)(s)--> phiphi)=[14(+6)(-5)(stat)+/-6(syst)]
      x 10(-6), BR(B+-->phiK+)=[7.6+/-1.3(stat)+/-0.6(syst)] x 10(-6), and A(CP)(B+-
      >phiK+)= -0.07+/-0.17(stat)+0.03 / -0.02(syst). Both decays are governed in the
      standard model by second order (penguin) b-->s(-)ss amplitudes.

PMID- 16090754
TI  - Emission of discrete vortex rings by a vibrating grid in superfluid 3He-B: a
      precursor to quantum turbulence.
AB  - We report a transition in the vorticity generated by a grid moving in the B phase
      of superfluid 3He at T<<T(c). The evolution of the vorticity after arresting the
      grid shows a dramatic change in the decay rate at a critical grid velocity. We
      believe this to reflect a sharp transition from ballistic vortex-ring production
      at low grid velocities to quantum turbulence at higher velocities and that
      independent isolated vortex rings provide the precursors to the developed
      turbulence. Furthermore we believe that this may be a feature of all quantum
      turbulence arising from repetitive mechanical agitation.

PMID- 16090755
TI  - Single impurity effect on the melting of nanoclusters.
AB  - We show by molecular dynamics simulations that the melting temperature of
      clusters can be tuned by selective doping. In fact, a single Ni or Cu impurity in
      Ag icosahedral clusters considerably increases the melting temperature even for
      sizes of more than a hundred atoms. The upward shift is correlated to the strain
      relaxation induced by a small central impurity in icosahedral clusters.

PMID- 16090756
TI  - The simplest quantum model supporting the Kibble-Zurek mechanism of topological
      defect production: Landau-Zener transitions from a new perspective.
AB  - It can be shown that the dynamics of the Landau-Zener model can be accurately
      described in terms of the Kibble-Zurek theory of the topological defect
      production in nonequilibrium phase transitions. The simplest quantum model
      exhibiting the Kibble-Zurek mechanism is presented. A new intuitive description
      of Landau-Zener dynamics is found.

PMID- 16090757
TI  - Surface diffusion: the low activation energy path for nanotube growth.
AB  - We present the temperature dependence of the growth rate of carbon nanofibers by
      plasma-enhanced chemical vapor deposition with Ni, Co, and Fe catalysts. We
      extrapolate a common low activation energy of 0.23-0.4 eV, much lower than for
      thermal deposition. The carbon diffusion on the catalyst surface and the
      stability of the precursor molecules, C2H2 or CH4, are investigated by ab initio
      plane wave density functional calculations. We find a low activation energy of
      0.4 eV for carbon surface diffusion on Ni and Co (111) planes, much lower than
      for bulk diffusion. The energy barrier for C2H2 and CH4 dissociation is at least
      1.3 eV and 0.9 eV, respectively, on Ni(111) planes or step edges. Hence, the rate
      limiting step for plasma-enhanced growth is carbon diffusion on the catalyst
      surface, while an extra barrier is present for thermal growth due to gas
      decomposition.

PMID- 16090758
TI  - Energy-dependent cancellation of diffraction spots due to surface roughening.
AB  - The low-energy electron diffraction (LEED) pattern of the step-kinked Pt{531}
      surface at 200 K shows energy-dependent cancellation of diffraction spots over
      unusually large energy ranges, up to 100 eV. This cannot be reproduced
      theoretically when a flat surface geometry is assumed. A relatively simple model
      of roughening, however, involving 0.25 ML of vacancies and adatoms leads to very
      good agreement with the experiment. The cancellation of intensities within a very
      narrow range of adatom or vacancy coverages is caused by the interference of
      electrons emerging from different heights but similar local environments. This is
      a rare example where the energy dependence of integrated LEED spot intensities is
      dramatically affected by the long-range arrangement of atoms.

PMID- 16090759
TI  - Strong coupling in a microcavity LED.
AB  - Thin films of polyelectrolyte/J aggregate dye bilayers with high absorption
      coefficient (6 nm thick with alpha approximately equal to 1.0 x 10(6) cm(-1))
      inserted in an optical microcavity enable the cavity quantum electrodynamic
      strong coupling limit to be reached at room temperature with a coupling strength
      (Rabi splitting) of 265 +/- 15 meV. By embedding these films in a resonant cavity
      organic LED structure, we demonstrate the first emissive electrically pumped
      exciton-polariton device.

PMID- 16090760
TI  - Many-body spin Berry phases emerging from the pi-flux state: competition between
      antiferromagnetism and the valence-bond-solid state.
AB  - We uncover new topology-related features of the pi-flux saddle-point solution of
      the D=2+1 Heisenberg antiferromagnet. We note that symmetries of the spinons
      sustain a built-in competition between antiferromagnetic (AFM) and valence-bond
      solid (VBS) orders, the two tendencies central to recent developments on quantum
      criticality. An effective theory containing an analogue of the Wess-Zumino-Witten
      term is derived, which generates quantum phases related to AFM monopoles with VBS
      cores, and reproduces Haldane's hedgehog Berry phases. The theory readily
      generalizes to pi-flux states for all D.

PMID- 16090761
TI  - U(1) gauge theory of the Hubbard model: spin liquid states and possible
      application to kappa-(BEDT-TTF)2Cu2(CN)3.
AB  - We formulate a U(1) gauge theory of the Hubbard model in the slave-rotor
      representation. From this formalism it is argued that spin liquid phases may
      exist near the Mott transition in the Hubbard model on triangular and honeycomb
      lattices at half filling. The organic compound kappa-(BEDT-TTF)2Cu2(CN)3 is a
      good candidate for the spin liquid state on a triangular lattice. We predict a
      highly unusual temperature dependence for the thermal conductivity of this
      material.

PMID- 16090762
TI  - Prediction of the capacitance line shape in two-channel quantum dots.
AB  - We propose a setup to realize two-channel Kondo physics using quantum dots. We
      discuss how the charge fluctuations on a small dot can be accessed by using a
      system of two single-electron transistors arranged in parallel. We derive a
      microscopic Hamiltonian description of the setup that allows us to make the
      connection with the two-channel Anderson model (of extended use in the context of
      heavy-fermion systems) and in turn make detailed predictions for the differential
      capacitance of the dot. Its line shape, which we determined precisely, shows a
      robust behavior that should be experimentally verifiable.

PMID- 16090763
TI  - Effect of magnetic impurities on energy exchange between electrons.
AB  - In order to probe quantitatively the effect of Kondo impurities on energy
      exchange between electrons in metals, we have compared measurements on two silver
      wires with dilute magnetic impurities (manganese) introduced in one of them. The
      measurement of the temperature dependence of the electron phase coherence time on
      the wires provides an independent determination of the impurity concentration.
      Quantitative agreement on the energy exchange rate is found with a theory by
      Goppert et al. that accounts for Kondo scattering of electrons on spin-1/2
      impurities.

PMID- 16090764
TI  - Magnetic correlations in the Hubbard model on triangular and Kagome lattices.
AB  - In order to study the magnetic properties of frustrated metallic systems, we
      present, for the first time, quantum Monte Carlo data on the magnetic
      susceptibility of the Hubbard model on triangular and kagome lattices. We show
      that the underlying lattice structure determines the nature and the doping
      dependence of the magnetic fluctuations. In particular, in the doped kagome case
      we find strong short-range magnetic correlations, which makes the metallic kagome
      systems a promising field for studies of superconductivity.

PMID- 16090765
TI  - Spin dynamics in the stripe phase of the cuprate superconductors.
AB  - Within a model that supports stripe spin and charge order coexisting with a d(x2
      y2)-wave superconducting phase, we study the self-consistently obtained
      electronic structure and the associated transverse dynamical spin susceptibility.
      In the coexisting phase of superconducting and static stripe order, the resulting
      particle-hole continuum can strongly damp parts of the low-energy spin-wave
      branches. This provides insight into recent inelastic neutron scattering data
      revealing the dispersion of the low-energy collective magnetic modes of lanthanum
      based cuprate superconductors.

PMID- 16090766
TI  - Quasi-two-dimensional diluted magnetic semiconductor systems.
AB  - We develop a theory for two-dimensional diluted magnetic semiconductor systems
      (e.g., Ga(1-x)Mn(x)As layers) where the itinerant carriers mediating the
      ferromagnetic interaction between the impurity local moments, as well as the
      local moments themselves, are confined in a two-dimensional layer. The theory
      includes exact spatial disorder effects associated with the random local moment
      positions within a disordered RKKY lattice field theory description. We predict
      the ferromagnetic transition temperature (T(c)) as well as the nature of the
      spontaneous magnetization. The theory includes disorder and finite carrier mean
      free path effects as well as the important correction arising from the finite
      temperature RKKY interaction, finding a strong density dependence of T(c) in
      contrast to the simple virtual crystal approximation.

PMID- 16090767
TI  - Scalable design of tailored soft pulses for coherent control.
AB  - We present a scalable scheme to design optimized soft pulses and pulse sequences
      for coherent control of interacting quantum many-body systems. The scheme is
      based on the cluster expansion and the time-dependent perturbation theory
      implemented numerically. This approach offers a dramatic advantage in numerical
      efficiency, and it is also more convenient than the commonly used Magnus
      expansion, especially when dealing with higher-order terms. We illustrate the
      scheme by designing 2nd-order self-refocusing pi pulses and a 6th-order 8-pulse
      refocusing sequence for a chain of qubits with nearest-neighbor couplings. We
      also discuss the performance of soft-pulse refocusing sequences in suppressing
      decoherence due to low-frequency environment.

PMID- 16090768
TI  - Quantum phase interference and spin-parity in Mn12 single-molecule magnets.
AB  - Magnetization measurements of Mn12 molecular nanomagnets with spin ground states
      of S=10 and S=19/2 show resonance tunneling at avoided energy level crossings.
      The observed oscillations of the tunnel probability as a function of the magnetic
      field applied along the hard anisotropy axis are due to topological quantum phase
      interference of two tunnel paths of opposite windings. Spin-parity dependent
      tunneling is established by comparing the quantum phase interference of integer
      and half-integer spin systems.

PMID- 16090769
TI  - Time resolved magnetization dynamics of ultrathin Fe(001) films: spin-pumping and
      two-magnon scattering.
AB  - The time-resolved magnetic response of ultrathin epitaxial Fe(001) films grown on
      GaAs(001) and covered by Au, Pd, and Cr capping layers was investigated by time
      and spatially resolved Kerr effect measurements. The magnetization was excited by
      an in-plane magnetic field pulse using the transient internal field generated at
      a Schottky barrier while the wavelength of the excitation (resonant mode) was
      roughly 4 microm. Each of the three cap layers affected the spin relaxation in a
      unique way. Au cap layers resulted in the bulk Gilbert damping of the Fe film. Pd
      cap layers caused an additional Gilbert damping due to spin-pump or spin-sink
      effects. Cr cap layers lead to a strong extrinsic damping which can be described
      by two-magnon scattering. In this case the strength of the extrinsic damping can
      be controlled by a field induced shift of the spin wave manifold with respect to
      the excited k vector.

PMID- 16090770
TI  - Pressure-induced anomalous phase transitions and colossal enhancement of
      piezoelectricity in PbTiO3.
AB  - We find an unexpected tetragonal-to-monoclinic-to-rhombohedral-to-cubic phase
      transition sequence induced by pressure, and a morphotropic phase boundary in a
      pure compound using first-principles calculations. Huge dielectric and
      piezoelectric coupling constants occur in the transition regions, comparable to
      those observed in the new complex single-crystal solid-solution piezoelectrics
      such as Pb(Mg(1/3)Nb(2/3))O3-PbTiO3, which are expected to revolutionize
      electromechanical applications. Our results show that morphotropic phase
      boundaries and giant piezoelectric effects do not require intrinsic disorder, and
      open the possibility of studying this effect in simple systems.

PMID- 16090771
TI  - Exact analysis of ESR shift in the spin-1/2 Heisenberg antiferromagnetic chain.
AB  - A systematic perturbation theory is developed for the ESR shift and is applied to
      the spin-1/2 Heisenberg antiferromagnetic chain with a general anisotropic
      exchange interaction. Using the Bethe ansatz technique, the resonance shift is
      obtained exactly for the whole range of temperature and magnetic field in the
      first order of the anisotropy. The obtained g shift strongly depends on magnetic
      fields at low temperature, showing a significant deviation from the previous
      classical result.

PMID- 16090772
TI  - Two-dimensional self-assembly in diblock copolymers.
AB  - Diblock copolymers confined to a two-dimensional surface may produce uniform
      features of macromolecular dimensions (approximately 10-100 nm). We present a
      mathematical model for nanoscale pattern formation in such polymers that captures
      the dynamic evolution of a solution of poly(styrene)-b-poly(ethylene oxide), PS-b
      PEO, in solvent at an air-water interface. The model has no fitting parameters
      and incorporates the effects of surface tension gradients, entanglement or
      vitrification, and diffusion. The resultant morphologies are quantitatively
      compared with experimental data.

PMID- 16090773
TI  - Onsets of anharmonicity in protein dynamics.
AB  - Two onsets of anharmonicity are observed in the dynamics of the protein lysozyme.
      One at T approximately 100 K appears in all samples regardless of hydration level
      and is consistent with methyl group rotation. The second, the well-known
      dynamical transition at T approximately 200-230 K, is only observed at a
      hydration level h greater than approximately 0.2 and is ascribed to the
      activation of an additional relaxation process. Its variation with hydration
      correlates well with variations of catalytic activity suggesting that the
      relaxation process is directly related to the activation of modes required for
      protein function.

PMID- 16090774
TI  - Discontinuous unbinding transitions of filament bundles.
AB  - Bundles of semiflexible polymers such as actin filaments are studied
      theoretically. The bundle formation is governed by attractive filament
      interactions mediated by cross-linking sticker molecules. Using a combination of
      analytical arguments and Monte Carlo simulations, it is shown that the formation
      of bundles of parallel filaments requires a threshold concentration of linkers
      which becomes independent of the filament number for large bundles. The unbinding
      of bundles happens in a single, discontinuous transition. We discuss the behavior
      of the bundle thickness at and below the transition. In the bound phase, large
      bundles tend to segregate into sub-bundles due to slow kinetics. Our results are
      in qualitative agreement with experiments on F-actin in the presence of the cross
      linking protein alpha-actinin.

PMID- 16090775
TI  - Spatiotemporal patterns of external noise-induced transitions in a bistable
      reaction-diffusion system: photoelectron emission microscopy experiments and
      modeling.
AB  - The rate of CO oxidation on Ir(111) surfaces exhibits bistability at T=500 K in a
      range of the CO fraction Y in the CO+O reactant gas flux. Measured CO2 rates as a
      function of the noise strength imposed on Y are well reproduced by parameter-free
      modeling. We present photoelectron emission microscopy measurements and 2D
      calculations of the spatiotemporal patterns of CO- and O-rich domains. The role
      of combined multiplicative and additive noise on Y for CO and O domain wall
      motion and island nucleation-growth-coalescence processes is analyzed.

PMID- 16090776
TI  - Evidence of many-particle interactions in two-dimensional charge-stabilized
      colloidal crystals.
AB  - Electrostatic interaction in two-dimensional colloidal crystals obeying the
      nonlinear Poisson-Boltzmann equation is studied numerically. The force constants
      which are the coefficients of the energy quadratic form of the crystal are
      obtained. Significant discrepancy between the results of computer experiments and
      predictions of the harmonic crystal theory based on the idea of pairwise
      interaction has been detected. Two simple parameters are introduced for uniform
      quantitative estimation of many-particle effects and validity of the
      approximation of nearest-neighbor interaction. It is shown that the contribution
      of many-particle interaction into the total electrostatic interaction in
      colloidal crystals is significant for a broad range of crystal lattice constants
      and particles' sizes.

PMID- 16090777
TI  - Segmented waves from a spatiotemporal transverse wave instability.
AB  - We observe traveling waves emitted from Turing spots in the chlorine dioxide
      iodine-malonic acid reaction. The newborn waves are continuous, but they break
      into segments as they propagate, and the propagation of these segments ultimately
      gives rise to spatiotemporal chaos. We model the wave-breaking process and the
      motion of the chaotic segments. We find stable segmented spirals as well. We
      attribute the segmentation to an interaction between front rippling via a
      transverse instability and front symmetry breaking by a fast-diffusing inhibitor
      far from the codimension-2 Hopf-Turing bifurcation, and the chaos to a secondary
      instability of the periodic segmentation.

PMID- 16090778
TI  - Anisotropy of sheared carbon-nanotube suspensions.
AB  - We measure the anisotropy of sheared carbon-nanotube suspensions for a broad
      range of concentration, aspect ratio, and strain rate using a variety of methods.
      Our measurements highlight the importance of excluded-volume interactions in the
      semidilute regime, with scaling in terms of a dimensionless shear rate. Our
      results also suggest that such interactions might be exploited to fractionate
      carbon nanotubes by length in simple shear flow.

PMID- 16090779
TI  - Long-range interactions in polymer melts: the anti-Casimir effect.
AB  - It is well known that small neutral particles normally tend to aggregate due to
      the van der Waals forces. We discover a new universal long-range interaction
      between solid objects in polymer media that is directly opposite the van der
      Waals attraction. The new force could reverse the sign of the net interaction,
      possibly leading to the net repulsion. This universal repulsion comes from the
      subtracted soft fluctuation modes, which are not present in the real polymer
      system, but rather are in its ideal counterpart. The predicted effect has a deep
      relation to the classical Casimir interactions, providing an unusual example of
      fluctuation-induced repulsion instead of normal attraction. That is why it is
      referred to as the anti-Casimir effect. We also find that the correlation
      function of monomer units in a concentrated solution of infinite polymer chains
      follows a power-law rather than an exponential decay at large distances.

PMID- 16090780
TI  - Spatiotemporal networks in addressable excitable media.
AB  - Spatiotemporal networks are studied in a photosensitive Belousov-Zhabotinsky
      medium that allows both local and nonlocal transmission of excitation. Local
      transmission occurs via propagating excitation waves, while nonlocal transmission
      takes place by nondiffusive jumps to destination sites linked to excited sites in
      the medium. Static, dynamic, and domain link networks are experimentally and
      computationally characterized. Transitions to synchronized behavior are exhibited
      with increasing link density, and power-law relations are observed for first
      coverage time as a function of link probability.

PMID- 16090781
TI  - Lossy data compression with random gates.
AB  - We introduce a new protocol for a lossy data compression algorithm which is based
      on constraint satisfaction gates. We show that the theoretical capacity of
      algorithms built from standard parity-check gates converges exponentially fast to
      the Shannon's bound when the number of variables seen by each gate increases. We
      then generalize this approach by introducing random gates. They have theoretical
      performances nearly as good as parity checks, but they offer the great advantage
      that the encoding can be done in linear time using the survey inspired decimation
      algorithm, a powerful algorithm for constraint satisfaction problems derived from
      statistical physics.

PMID- 16090782
TI  - Attosecond double-slit experiment.
AB  - A new scheme for a double-slit experiment in the time domain is presented. Phase
      stabilized few-cycle laser pulses open one to two windows (slits) of attosecond
      duration for photoionization. Fringes in the angle-resolved energy spectrum of
      varying visibility depending on the degree of which-way information are measured.
      A situation in which one and the same electron encounters a single and a double
      slit at the same time is observed. The investigation of the fringes makes
      possible interferometry on the attosecond time scale. From the number of visible
      fringes, for example, one derives that the slits are extended over about 500 as.

PMID- 16090783
TI  - Atomic quantum simulator for lattice gauge theories and ring exchange models.
AB  - We present the design of a ring exchange interaction in cold atomic gases
      subjected to an optical lattice using well-understood tools for manipulating and
      controlling such gases. The strength of this interaction can be tuned
      independently and describes the correlated hopping of two bosons. We discuss a
      setup where this coupling term may allow for the realization and observation of
      exotic quantum phases, including a deconfined insulator described by the Coulomb
      phase of a three-dimensional U(1) lattice gauge theory.

PMID- 16090784
TI  - Atomic gases at negative kinetic temperature.
AB  - We show that thermalization of the motion of atoms at negative temperature is
      possible in an optical lattice, for conditions that are feasible in current
      experiments. We present a method for reversibly inverting the temperature of a
      trapped gas. Moreover, a negative-temperature ensemble can be cooled (reducing
      |T|) by evaporation of the lowest-energy particles. This enables the attainment
      of the Bose-Einstein condensation phase transition at negative temperature.

PMID- 16090785
TI  - Test of Lorentz invariance in electrodynamics using rotating cryogenic sapphire
      microwave oscillators.
AB  - We present the first results from a rotating Michelson-Morley experiment that
      uses two orthogonally orientated cryogenic sapphire resonator oscillators
      operating in whispering gallery modes near 10 GHz. The experiment is used to test
      for violations of Lorentz invariance in the framework of the photon sector of the
      standard model extension (SME), as well as the isotropy term of the Robertson
      Mansouri-Sexl (RMS) framework. In the SME we set a new bound on the previously
      unmeasured kappa(ZZ)(e-) component of 2.1(5.7) x 10(-14), and set more stringent
      bounds by up to a factor of 7 on seven other components. In the RMS a more
      stringent bound of -0.9(2.0) x 10(-10) on the isotropy parameter, P(MM) = delta
      beta + 1 / 2 is set, which is more than a factor of 7 improvement.

PMID- 16090786
TI  - Entanglement of a photon and a collective atomic excitation.
AB  - We describe a new experimental approach to probabilistic atom-photon (signal)
      entanglement. Two qubit states are encoded as orthogonal collective spin
      excitations of an unpolarized atomic ensemble. After a programmable delay, the
      atomic excitation is converted into a photon (idler). Polarization states of both
      the signal and the idler are recorded and are found to be in violation of the
      Bell inequality. Atomic coherence times exceeding several microseconds are
      achieved by switching off all the trapping fields--including the quadrupole
      magnetic field of the magneto-optical trap--and zeroing out the residual ambient
      magnetic field.

PMID- 16090787
TI  - Quantum key distribution with blind polarization bases.
AB  - We propose a new quantum key distribution scheme that uses the blind polarization
      basis. In our scheme the sender and the receiver share key information by
      exchanging qubits with arbitrary polarization angles without basis
      reconciliation. As only random polarizations are transmitted, our protocol is
      secure even when a key is embedded in a not-so-weak coherent-state pulse. We show
      its security against the photon-number splitting attack and the impersonation
      attack.

PMID- 16090788
TI  - Optimizing linear optics quantum gates.
AB  - In this Letter, the problem of finding optimal success probabilities of linear
      optics quantum gates is linked to the theory of convex optimization. It is shown
      that by exploiting this link, upper bounds for the success probability of
      networks realizing single-mode gates can be derived, which hold in generality for
      postselected networks of arbitrary size, any number of auxiliary modes, and
      arbitrary photon numbers. As a corollary, the previously formulated conjecture is
      proven that the optimal success probability of a nonlinear sign shift without
      feedforward is 1/4, a gate playing the central role in the scheme of Knill
      Laflamme-Milburn for quantum computation. The concept of Lagrange duality is
      shown to be applicable to provide rigorous proofs for such bounds, although the
      original problem is a difficult nonconvex problem in infinitely many objective
      variables. The versatility of this approach is demonstrated.

PMID- 16090789
TI  - Faithful qubit distribution assisted by one additional qubit against collective
      noise.
AB  - We propose a distribution scheme of polarization states of a single photon over a
      collective-noise channel. By adding one extra photon with a fixed polarization,
      we can protect the state against collective noise via a parity-check measurement
      and postselection. While the scheme succeeds only probabilistically, it is
      simpler and more flexible than the schemes utilizing decoherence-free subspace.
      An application to the Bennett-Brassard 1984 protocol through a collective-noise
      channel, which is robust to the Trojan horse attack, is also given.

PMID- 16090790
TI  - Concurrence of arbitrary dimensional bipartite quantum states.
AB  - We derive an analytical lower bound for the concurrence of a bipartite quantum
      state in arbitrary dimension. A functional relation is established relating
      concurrence, the Peres-Horodecki criterion, and the realignment criterion. We
      demonstrate that our bound is exact for some mixed quantum states. The
      significance of our method is illustrated by giving a quantitative evaluation of
      entanglement for many bound entangled states, some of which fail to be identified
      by the usual concurrence estimation method.

PMID- 16090791
TI  - Delay-induced excitability.
AB  - We analyze the stochastic dynamics of a bistable system under the influence of
      time-delayed feedback. Assuming an asymmetric potential, we show the existence of
      a regime in which the system dynamics displays excitability by calculating the
      relevant residence time distributions and power spectra. Experimentally we then
      observe this behavior in the polarization dynamics of a vertical cavity surface
      emitting laser with optoelectronic feedback. Extending these observations to two
      dimensional systems with diffusive coupling, we finally show numerically that
      delay-induced excitability can lead to the appearance of propagating wave fronts
      and spirals.

PMID- 16090792
TI  - Entropy production along a stochastic trajectory and an integral fluctuation
      theorem.
AB  - For stochastic nonequilibrium dynamics like a Langevin equation for a colloidal
      particle or a master equation for discrete states, entropy production along a
      single trajectory is studied. It involves both genuine particle entropy and
      entropy production in the surrounding medium. The integrated sum of both
      Delatas(tot) is shown to obey a fluctuation theorem (exp([-Deltas(tot) = 1 for
      arbitrary initial conditions and arbitrary time-dependent driving over a finite
      time interval.

PMID- 16090793
TI  - Histogram reweighting method for dynamic properties.
AB  - The histogram reweighting technique, widely used to analyze Monte Carlo data, is
      shown to be applicable to dynamic properties obtained from molecular dynamics
      simulations. The theory presented here is based on the fact that the correlation
      functions in systems in thermodynamic equilibrium are averages over initial
      conditions of trajectory functions, the latter depending on the volume of the
      system, the total number of particles, and the classical Hamiltonian. Thus, the
      well-known histogram reweighting method can be almost straightforwardly applied
      to reconstruct the probability distribution of initial states at different
      thermodynamic conditions, without extra computational effort. Correlation
      functions and transport coefficients are obtained with this method from few
      simulation data sets.

PMID- 16090794
TI  - Limits on variations in fundamental constants from 21-cm and ultraviolet Quasar
      absorption lines.
AB  - Quasar absorption spectra at 21-cm and UV rest wavelengths are used to estimate
      the time variation of x [triple-bond] alpha(2)g(p)mu, where alpha is the fine
      structure constant, g(p) the proton g factor, and m(e)/m(p) [triple-bond] mu the
      electron/proton mass ratio. Over a redshift range 0.24 < or = zeta(abs) < or =
      2.04, (Deltax/x)(weighted)(total) = (1.17 +/- 1.01) x 10(-5). A linear fit gives
      x/x = (-1.43 +/- 1.27) x 10(-15) yr(-1). Two previous results on varying alpha
      yield the strong limits Deltamu/mu = (2.31 +/- 1.03) x 10(-5) and
      Deltamu/mu=(1.29 +/- 1.01) x10(-5). Our sample, 8 x larger than any previous,
      provides the first direct estimate of the intrinsic 21-cm and UV velocity
      differences 6 km s(-1).

PMID- 16090795
TI  - Escaping the large fine-tuning and little hierarchy problems in the next to
      minimal supersymmetric model and h --> aa decays.
AB  - We demonstrate that the next to minimal supersymmetric model can have small fine
      tuning and modest top-squark mass while still evading all experimental
      constraints. For small tan(beta (large tan(beta), the relevant scenarios are such
      that there is always (often) a standard-model-like Higgs boson that decays to two
      lighter--possibly much lighter--Higgs pseudoscalars.

PMID- 16090797
TI  - Evidence for B0 --> D+ D- and observation of B- --> D0D- and B- -->D0D*- decays.
AB  - We report evidence for B(0) --> D(0)D(-) and the first observation of the decay
      modes B(-) --> D(0)D(-) and B(-) --> D(0)D(*-) based on a sample of 152 x 10(6)
      BB events collected by the Belle detector at KEKB. The branching fractions for
      B(0) --> D(+) D(-), B--->D(0)D(-), and B--> D(0)D(*-) are found to be (1.91 +/-
      0.51 +/- 0.30) x10(-4), (4.83 +/- 0.78 +/- 0.58) x 10(-4), and (4.57 +/- 0.71 +/-
      0.56) x 10(-4), respectively. Charge asymmetries in the B---> D(0)D(-) and B(-) -
      > D(0)D(*-) channels are consistent with zero.

PMID- 16090802
TI  - Isospin dependence in the odd-even staggering of nuclear binding energies.
AB  - The FRS-ESR facility at GSI provides unique conditions for precision measurements
      of large areas on the nuclear mass surface in a single experiment. Values for
      masses of 604 neutron-deficient nuclides (30 < or = Z < or = 92) were obtained
      with a typical uncertainty of 30 microu. The masses of 114 nuclides were
      determined for the first time. The odd-even staggering (OES) of nuclear masses
      was systematically investigated for isotopic chains between the proton shell
      closures at Z = 50 and Z = 82. The results were compared with predictions of
      modern nuclear models. The comparison revealed that the measured trend of OES is
      not reproduced by the theories fitted to masses only. The spectral pairing gaps
      extracted from models adjusted to both masses, and density related observables of
      nuclei agree better with the experimental data.

PMID- 16090803
TI  - Shell model description of the decay out of the superdeformed band of 36Ar.
AB  - Large scale shell model calculations in the valence space spanned by two major
      oscillator shells (sd and pf) describe simultaneously the superdeformed excited
      band of 36Ar and its spherical ground state. We explain the appearance of this
      superdeformed band at low excitation energy as a consequence of the very large
      quadrupole correlation energy of the configurations with many particles and many
      holes (np-nh) relative to the normal filling of the spherical mean field orbits
      (0p-0h). We study the mechanism of mixing between the different configurations to
      understand why the superdeformed band survives and how it finally decays into the
      low-lying spherical states via the indirect mixing of the 0p-0h and 4p-4h
      configurations.

PMID- 16090804
TI  - Microscopic theory of the two-proton radioactivity.
AB  - We formulate a theory of the two-proton radioactivity based on the real-energy
      continuum shell model. This microscopic approach is applied to describe the two
      proton decay of the 1(-)(2) state in 18Ne.

PMID- 16090805
TI  - Control of population flow in coherently driven quantum ladders.
AB  - A technique for adiabatic control of the population flow through a preselected
      decaying excited level in a three-level quantum ladder is presented. The
      population flow through the intermediate or upper level is controlled efficiently
      and robustly by varying the pulse delay between a pair of partly overlapping
      coherent laser pulses. The technique is analyzed theoretically and demonstrated
      in an experiment with Na2 molecules.

PMID- 16090806
TI  - Exact nondipole Kramers-Henneberger form of the light-atom hamiltonian: an
      application to atomic stabilization and photoelectron energy spectra.
AB  - The exact nondipole minimal-coupling Hamiltonian for an atom interacting with an
      explicitly time- and space-dependent laser field is transformed into the rest
      frame of a classical free electron in the laser field, i.e., into the Kramers
      Henneberger frame. The new form of the Hamiltonian is used to study nondipole
      effects in the high-intensity, high-frequency regime. Fully three-dimensional
      nondipole ab initio wave packet calculations show that the ionization probability
      may decrease for increasing field strength. We identify a unique signature for
      the onset of this dynamical stabilization effect in the photoelectron spectrum.

PMID- 16090807
TI  - Vorticity cutoff in nonlinear photonic crystals.
AB  - Using group-theory arguments, we demonstrate that, unlike in homogeneous media,
      no symmetric vortices of arbitrary order can be generated in two-dimensional (2D)
      nonlinear systems possessing a discrete-point symmetry. The only condition needed
      is that the nonlinearity term exclusively depends on the modulus of the field. In
      the particular case of 2D periodic systems, such as nonlinear photonic crystals
      or Bose-Einstein condensates in periodic potentials, it is shown that the
      realization of discrete symmetry forbids the existence of symmetric vortex
      solutions with vorticity higher than two.

PMID- 16090808
TI  - Effects of spatial nonuniformity on laser dynamics.
AB  - Semiclassical equations of lasing dynamics are rederived for a lasing medium in a
      cavity with a spatially nonuniform dielectric constant. The nonuniformity causes
      a radiative coupling between modes of the empty cavity, which results in a
      renormalization of self- and cross-saturation coefficients. Possible
      manifestations of these effects in random lasers are discussed.

PMID- 16090809
TI  - From flow to map in an experimental high-dimensional electro-optic nonlinear
      delay oscillator.
AB  - An optoelectronic nonlinear delay oscillator seeded by a pulsed laser source is
      used to experimentally demonstrate a new transition scenario for the general
      class of delay differential dynamics, from continuous to discrete time behavior.
      This transition scenario differs from the singular limit map, or adiabatic
      approximation model that is usually considered. The transition from the map to
      the flow is observed when increasing the pulse repetition rate. The mechanism of
      this transition opens the way to new interpretations of the general properties of
      delay differential dynamics, which are universal features of many other
      scientific domains. We anticipate that the nonlinear delay oscillator
      architecture presented here will have significant applications in chaotic
      communication systems.

PMID- 16090810
TI  - Eikonal method for calculation of coherence functions.
AB  - A method is presented for computing the cross-spectral density of a special class
      of partially coherent fields in which the coherent modes obey an eikonal
      equation. This method allows for statistical analysis of optical systems based on
      simple ray tracing.

PMID- 16090811
TI  - Dynamics of a bouncing dimer.
AB  - We investigate the dynamics of a dimer bouncing on a vertically oscillated plate.
      The dimer, composed of two spheres rigidly connected by a light rod, exhibits
      several modes depending on initial and driving conditions. The first excited mode
      has a novel horizontal drift in which one end of the dimer stays on the plate
      during most of the cycle, while the other end bounces in phase with the plate.
      The speed and direction of the drift depend on the aspect ratio of the dimer. We
      employ event-driven simulations based on a detailed treatment of frictional
      interactions between the dimer and the plate in order to elucidate the nature of
      the transport mechanism in the drift mode.

PMID- 16090812
TI  - Plasma line emission during single-bubble cavitation.
AB  - Emission lines from transitions between high-energy states of noble-gas atoms
      (Ne, Ar, Kr, and Xe) and ions (Ar(+), Kr(+), and Xe(+)) formed and excited during
      single-bubble cavitation in sulfuric acid are reported. The excited states
      responsible for these emission lines range 8.3 eV (for Xe) to 37.1 eV (for Ar(+))
      above the respective ground states. Observation of emission lines allows for
      identification of intracavity species responsible for light emission; the
      populated energy levels indicate the plasma generated during cavitation is
      comprised of highly energetic particles.

PMID- 16090813
TI  - Understanding the loading dependence of self-diffusion in carbon nanotubes.
AB  - The influence of flexible walls on the self-diffusion of CH4 in an isolated
      single walled carbon nanotube, as an example, is studied by molecular dynamics
      simulations. By simulating the carbon nanotube as a flexible framework we
      demonstrate that the flexibility has a crucial influence on self-diffusion at low
      loadings. We show how this influence can be incorporated in a simulation of a
      rigid nanotube by using a Lowe-Andersen thermostat which works on interface-fluid
      collisions. The reproduction of the results of a flexible carbon nanotube by a
      rigid nanotube simulation is excellent.

PMID- 16090814
TI  - Unstable fingering patterns of Hele-Shaw flows as a dispersionless limit of the
      Kortweg-de vries hierarchy.
AB  - We show that unstable fingering patterns of two-dimensional flows of viscous
      fluids with open boundary are described by a dispersionless limit of the Korteweg
      de Vries hierarchy. In this framework, the fingering instability is linked to a
      known instability leading to regularized shock solutions for nonlinear waves, in
      dispersive media. The integrable structure of the flow suggests a dispersive
      regularization of the finite-time singularities.

PMID- 16090815
TI  - Nonlinear dynamics of inviscid reduced MHD plasmas: the appearance of Quasi
      Single-helicity states.
AB  - The nonlinear dynamics of an inviscid magnetohydrodynamic system in a low-beta
      plasma is investigated through a simplified model obtained by a Galerkin
      projection. We show that a single Fourier mode dominates over the whole energy
      spectrum, a self-organization mechanism of turbulence being responsible for this
      nonlinear effect. Our results are in agreement with observations of an analogous
      phenomenon, say, the emergence of a quasi-single-helicity state both in numerical
      simulations and real experiments in reversed field pinch laboratory plasmas.

PMID- 16090816
TI  - Dynamic and stagnating plasma flow leading to magnetic-flux-tube collimation.
AB  - Highly collimated, plasma-filled magnetic-flux tubes are frequently observed on
      galactic, stellar, and laboratory scales. We propose that a single, universal
      magnetohydrodynamic pumping process explains why such collimated, plasma-filled
      magnetic-flux tubes are ubiquitous. Experimental evidence from carefully
      diagnosed laboratory simulations of astrophysical jets confirms this assertion
      and is reported here. The magnetohydrodynamic process pumps plasma into a
      magnetic-flux tube and the stagnation of the resulting flow causes this flux tube
      to become collimated.

PMID- 16090817
TI  - Suppression of Hall-term effects by gyroviscous cancellation in steady
      collisionless magnetic reconnection.
AB  - The formation of an ion-dissipation region, in which motions of electrons and
      ions decouple and fast magnetic reconnection occurs, is demonstrated during a
      steady state of two-dimensional collisionless driven reconnection by means of
      full-particle simulations. The Hall-term effect is suppressed due to the
      gyroviscous cancellation at scales between the ion-skin depth and ion-meandering
      orbit scale, and thus ions are tied to the magnetic field. The ion frozen-in
      constraint is strongly broken by nongyrotropic pressure tensor effects due to ion
      meandering motion, and thus the ion-dissipation region is formed at scales below
      the ion-meandering-orbit scale. A similar process is observed in the formation of
      an electron-dissipation region. These two dissipation regions are clearly
      observed in an out-of-plane current density profile.

PMID- 16090818
TI  - Influence of indenter tip geometry on elastic deformation during nanoindentation.
AB  - Nanoindentation with a Berkovich indenter is commonly used to investigate the
      mechanical behavior of small volumes of materials. To date, most investigators
      have made the simplifying assumption that the tip is spherical. In reality,
      indenter tips are much more complex. Here, we develop a new method to describe
      the tip shape using the experimentally determined area function of the indenter
      at small depths (0-100 nm). Our analysis accurately predicts the elastic load
      displacement curve and allows the theoretical strength of a material to be
      determined from pop-in data. Application of our new method to single crystal
      Cr3Si shows that the predicted theoretical strengths are within 12% of the ideal
      strength G/2pi, where G is the shear modulus.

PMID- 16090796
TI  - Search for lepton flavor violation in the decay tau+/- --> mu+ gamma.
AB  - A search for the nonconservation of lepton flavor number in the decay tau(+/-) -
      > mu(+/-) has been performed using 2.07 x 10(8) e(+ )e(-) tau(+) tau(-) events
      produced at a center-of-mass energy near 10.58 GeV with the BABAR detector at the
      PEP-II storage ring. We find no evidence for a signal and set an upper limit on
      the branching ratio of Beta(tau(+/-) --> mu(+/-) gamma) < 6.8 x 10(-8) at 90%
      confidence level.

PMID- 16090798
TI  - Search for the rare leptonic decay B--->tau-nutau.
AB  - We present a search for the decay B(-)--> tau(-)nu(tau) in a sample of 88.9 x
      10(6) BB pairs recorded with the BABAR detector at the Stanford Linear
      Accelerator Center B factory. One of the two B mesons from the Gamma(4S) is
      reconstructed in a hadronic or a semileptonic final state, and the decay products
      of the other B in the event are analyzed for consistency with a B(-) --> tau(
      )nu(tau) decay. We find no evidence of a signal and set an upper limit on the
      branching fraction of B(B(-) --> tau(-) nu(tau)) < 4.2 x 10(-4) at the 90%
      confidence level.

PMID- 16090819
TI  - Single C59N molecule as a molecular rectifier.
AB  - We report a new kind of experimental realization of a molecular rectifier, which
      is based on a single azafullerene C59N molecule in a double-barrier tunnel
      junction via the single electron tunneling effect. An obvious rectifying effect
      is observed. The positive onset voltage is about 0.5-0.7 V, while the negative
      onset voltage is about 1.6-1.8 V. Theoretical analyses show that the half
      occupied molecular orbital of the C59N molecule and the asymmetric shift of the
      molecular Fermi level when the molecule is charged are responsible for the
      molecular rectification.

PMID- 16090799
TI  - Improved Measurement of the Cabibbo-Kobayashi-Maskawa angle alpha using B0(B) -->
      rho+rho- decays.
AB  - We present results from an analysis of B(0)B(0)--> rho(+)rho(-) using 232 x 10(6)
      Gamma (4S) --> BB decays collected with the BABAR detector at the PEP-II
      asymmetric-energy B factory at SLAC. We measure the longitudinal polarization
      fraction f(L) = 0.978 +/- 0.014(stat) + 0.021 / -0.029(syst) and the CP-violating
      parameters S(L)= -0.33 +/- 0.24(stat) + 0.08 / -0.14(syst) and C(L)= -0.03 +/-
      0.18(stat) +/- 0.09(syst). Using an isospin analysis of B --> rhorho decays, we
      determine the unitarity triangle parameter alpha. The solution compatible with
      the standard model is alpha = (100 +/- 13) degrees.

PMID- 16090820
TI  - First principles calculations of mechanical properties of 4,4'-bipyridine
      attached to Au nanowires.
AB  - A first attempt is made to calculate the forces involved in the breaking of
      nanowires consisting of a molecule attached to nanosized metallic pieces. As a
      model system, we consider different Au nanowires connected by a 4,4(')-bipyridine
      or pyrazine molecule, for which density functional calculations were performed at
      different elongations. The geometry of the system was optimized for different
      forces applied. In all cases the calculated maximum forces were close to 1 nN,
      which is of the order of the experimental values, and smaller than the
      corresponding to the rupture of the Au-Au chain (1.5-1.6 nN). When 4,4(')
      bipyridine is attached to Au monoatomic nanowire, the maximum force required to
      break the Au-Au bond may be lowered to values close to that obtain to break the
      Au-N bond, but when 4,4(')-bipyridine is attached to small Au clusters, the
      breaking of the nanowire takes place at the Au-N bond only.

PMID- 16090800
TI  - Measurement of the branching fraction of Gamma(4S) --> B0B0.
AB  - We report the first measurement of the branching fraction f(00) for Gamma(4S) -->
      B(0)B(0). The data sample consists of 81.7 fb(-1) collected at the Gamma(4S)
      resonance with the BABAR detector at the SLAC PEP-II asymmetric-energy e(+)e(-)
      storage ring. Using partial reconstruction of the decay B(0) --> D(*+) l(-)nu(l)
      in which only the charged lepton and the soft pion from the decay D(*+) -->
      D(0)pi(+) are reconstructed, we obtain f(00) = 0.487 +/- 0.010(stat) +/-
      0.008(syst). Our result does not depend on the branching fractions of B(0) -->
      D(*+)l(-)nu(l) and D(*+) --> D(0)pi(+) decays, on the ratio of the charged and
      neutral B meson lifetimes, nor on the assumption of isospin symmetry.

PMID- 16090801
TI  - Search for strange-pentaquark production in e+e- annihilation at sqrt[s] = 10.58
      GeV.
AB  - We search for strange-pentaquark states that have been previously reported by
      other experiments--the Theta (1540)(+), Xi(5)(1860)(--), and Xi(5)(1860)(0)--in
      123 fb(-1) of data recorded with the BABAR detector at the PEP-II e(+)e(-)
      storage ring. We find no evidence for these states and set 95% confidence level
      upper limits on the number of Theta(1540)(+) and Xi(5)(1860)(--) pentaquarks
      produced per e(+)e(-) annihilation into qq and Gamma(4S) decay. For qq events the
      Theta(1540)(+) [Xi(5)(1860)(--)] limit is about 8 [4] times lower than the rates
      measured for ordinary baryons of similar mass.

PMID- 16090822
TI  - Forced chemical mixing in alloys driven by plastic deformation.
AB  - Molecular dynamics simulations of forced atomic mixing in crystalline binary
      alloys during plastic deformation at 100 K are performed. Nearly complete atomic
      mixing is observed in systems that have a large positive heat mixing and in
      systems with a large lattice mismatch. Only systems that contained a hard
      precipitate in a soft matrix do not mix. The amount of mixing is quantified by
      defining a mean square relative displacement of pairs of atoms, sigma(2)(R,t),
      that were initially separated by a distance R. Analysis of sigma(2)(R,t) and
      visual inspection of the displacement fields reveal that forced mixing results
      from dislocation glide, and that it resembles the forced mixing of a substance
      advected by a turbulent flow. Consideration of sigma(2)(R,t) also provides a
      rationalization of compositional self-organization during plastic deformation at
      higher temperatures.

PMID- 16090821
TI  - Microscopic mechanism of water diffusion in glucose glasses.
AB  - The preservation of biomaterials depends critically on the mobility of water in
      the glassy state, manifested as a secondary beta relaxation and diffusion. We use
      coarse grain simulations to elucidate the molecular mechanism underlying the
      relaxations for water-glucose glass, finding two pathways for water diffusion:
      (i) water jumps into neighbor water positions (linking to water structure), and
      (ii) water jumps into glucose positions (coupling to glucose rotation). This work
      suggests strategies for enhancing preservation by stiffening the segmental
      motions of the carbohydrates.

PMID- 16090824
TI  - Intertwined electronic and structural phase transitions in the In/Si(111)
      interface.
AB  - The structural (4 x 1) to (8 x 2) transition and the electronic metal to
      semimetal transition at the In/Si interface are studied with scanning tunneling
      microscopy and spectroscopy. Both transitions are gradual, resulting in a complex
      domain structure in the transition temperature regime. At these intermediate
      temperatures, the metallic (4 x 1) and semimetallic (8 x 2) domains coexist with
      each other and with new nanophases. By probing the two intertwined but
      distinguishable transitions at the atomic level, the interaction between
      different phases is visualized directly.

PMID- 16090825
TI  - Optical study of interactions in a d-electron Kondo lattice with ferromagnetism.
AB  - We report on a comprehensive optical, transport, and thermodynamic study of the
      Zintl compound Yb(14)MnSb(11), demonstrating that it is the first ferromagnetic
      Kondo lattice compound in the underscreened limit. We propose a scenario whereby
      the combination of Kondo and Jahn-Teller effects provides a consistent
      explanation of both transport and optical data.

PMID- 16090826
TI  - Universal scaling and a novel quantum critical behavior of CeRhSb1-xSnx.
AB  - We observe and explain a universal scaling rhochi = const for the electrical
      resistivity rho with the inverse magnetic susceptibility chi(-1) for the Kondo
      insulator CeRhSb(1-x)Snx. In the regime where the Kondo gap disappears (x >
      0.12), the system forms a non-Fermi liquid (NFL), which transforms into a Fermi
      liquid at higher temperature. The NFL behavior is associated with the presence of
      a novel quantum critical point (QCP) at the Kondo insulator-correlated metal
      boundary. The divergent behavior of the resistivity, the susceptibility, and the
      specific heat has been observed when approaching the QCP from the metallic side
      and is interpreted as due to the competition between the Kondo and the intersite
      magnetic correlations.

PMID- 16090823
TI  - Disorder in DNA-linked gold nanoparticle assemblies.
AB  - We report experimental observations on the effect of disorder on the phase
      behavior of DNA-linked nanoparticle assemblies. Variation in DNA linker lengths
      results in different melting temperatures of the DNA-linked nanoparticle
      assemblies. We observed an unusual trend of a nonmonotonic "zigzag" pattern in
      the melting temperature as a function of DNA linker length. Linker DNA resulting
      in unequal DNA duplex lengths introduces disorder and lowers the melting
      temperature of the nanoparticle system. Comparison with free DNA thermodynamics
      shows that such an anomalous zigzag pattern does not exist for free DNA duplex
      melting, which suggests that the disorder introduced by unequal DNA duplex
      lengths results in this unusual collective behavior of DNA-linked nanoparticle
      assemblies.

PMID- 16090827
TI  - Exact results for strongly correlated fermions in 2 + 1 dimensions.
AB  - We derive exact results for a model of strongly interacting spinless fermions
      hopping on a two-dimensional lattice. By exploiting supersymmetry, we find the
      number and type of ground states exactly. Exploring various lattices and limits,
      we show how the ground states can be frustrated, quantum critical, or combine
      frustration with a Wigner crystal. We show that on generic lattices the model is
      in an exotic "superfrustrated" state characterized by an extensive ground-state
      entropy.

PMID- 16090828
TI  - Dephasing and weak localization in disordered Luttinger liquid.
AB  - We study the transport properties of interacting electrons in a disordered
      quantum wire within the framework of the Luttinger liquid model. The conductivity
      at finite temperature is nonzero only because of inelastic electron-electron
      scattering. We demonstrate that the notion of weak localization is applicable to
      the strongly correlated one-dimensional electron system. We calculate the
      relevant dephasing rate, which for spinless electrons is governed by the
      interplay of electron-electron interaction and disorder, thus vanishing in the
      clean limit.

PMID- 16090829
TI  - Nonequilibrium spin Hall accumulation in ballistic semiconductor nanostructures.
AB  - We demonstrate that the flow of a longitudinal unpolarized current through a
      ballistic two-dimensional electron gas with Rashba spin-orbit coupling will
      induce a nonequilibrium spin accumulation which has opposite signs for the two
      lateral edges and is, therefore, the principal observable signature of the spin
      Hall effect in two-probe semiconductor nanostructures. The magnitude of its out
      of-plane component is gradually diminished by static disorder, while it can be
      enhanced by an in-plane transverse magnetic field. Moreover, our prediction of
      the longitudinal component of the spin Hall accumulation, which is insensitive to
      the reversal of the bias voltage, offers direct evidence to differentiate
      experimentally between the extrinsic, intrinsic, and mesoscopic spin Hall
      mechanisms.

PMID- 16090830
TI  - Lifetimes of stark-shifted image states.
AB  - The inelastic lifetimes of electrons in image-potential states at Cu(100) that
      are Stark shifted by the electrostatic tip-sample interaction in the scanning
      tunneling microscope are calculated using the many-body GW approximation. The
      results demonstrate that in typical tunneling conditions the image state
      lifetimes are significantly reduced from their field-free values. The Stark shift
      to higher energies increases the number of inelastic scattering channels that are
      available for decay, with field-induced changes in the image state wave function
      increasing the efficiency of the inelastic scattering through greater overlap
      with final state wave functions.

PMID- 16090831
TI  - Channel plasmon-polariton guiding by subwavelength metal grooves.
AB  - We report on realization of channel plasmon-polariton (CPP) propagation along a
      subwavelength metal groove. Using imaging with a near-field microscope and end
      fire coupling with a tapered fiber connected to a tunable laser at
      telecommunication wavelengths (1425-1620 nm), we demonstrate low-loss
      (propagation length approximately 100 microm) and well-confined (mode width
      approximately 1.1 microm) CPP guiding along a triangular 0.6 microm-wide and 1
      microm-deep groove in gold. We develop a simple model based on the effective
      index method that accounts for the main features of CPP guiding and provides a
      clear physical picture of this phenomenon.

PMID- 16090832
TI  - Nonequilibrium noise as a probe of the Kondo effect in mesoscopic wires.
AB  - We study the nonequilibrium noise in mesoscopic diffusive wires hosting magnetic
      impurities. We find that the shot-noise to current ratio develops a peak at
      intermediate source-drain biases of the order of the Kondo temperature. The
      enhanced impurity contribution at intermediate biases is also manifested in the
      effective distribution. The predicted peak represents an increased inelastic
      scattering rate at the nonequilibrium Kondo crossover.

PMID- 16090833
TI  - Metal work-function changes induced by organic adsorbates: a combined
      experimental and theoretical study.
AB  - The role of molecular dipole moment, charge transfer, and Pauli repulsion in
      determining the work-function change (Deltaphi) at organic-metal interfaces has
      been elucidated by a combined experimental and theoretical study of
      (CH(3)S)(2)/Au(111) and CH(3)S/Au(111). Comparison between experiment and theory
      allows us to determine the origin of the interface dipole layer for both phases.
      For CH(3)S/Au(111), Deltaphi can be ascribed almost entirely to the dipole moment
      of the CH(3)S layer. For (CH(3)S)(2)/Au(111), a Pauli repulsion mechanism occurs.
      The implications of these results on the interpretation of Deltaphi in the
      presence of strongly and weakly adsorbed molecules is discussed.

PMID- 16090834
TI  - Models of environment and T1 relaxation in Josephson charge qubits.
AB  - A theoretical interpretation of the recent experiments of Astafiev et al. on the
      T1-relaxation rate in Josephson charge qubits is proposed. The experimentally
      observed reproducible nonmonotonic dependence of T1 on the splitting E(J) of the
      qubit levels suggests further specification of the previously proposed models of
      the background charge noise. From our point of view the most promising is the
      "Andreev fluctuator" model of the noise. In this model the fluctuator is a Cooper
      pair that tunnels from a superconductor and occupies a pair of localized
      electronic states. Within this model one can naturally explain both the average
      linear T1(E(J)) dependence and the irregular fluctuations.

PMID- 16090835
TI  - Depth profile of uncompensated spins in an exchange bias system.
AB  - We have used the unique spatial sensitivity of polarized neutron and soft x-ray
      beams in reflection geometry to measure the depth dependence of magnetization
      across the interface between a ferromagnet and an antiferromagnet. The net
      uncompensated magnetization near the interface responds to applied field, while
      uncompensated spins in the antiferromagnet bulk are pinned, thus providing a
      means to establish exchange bias.

PMID- 16090836
TI  - Finite tunneling spin polarization at the compensation point of rare-earth-metal
      transition-metal alloys.
AB  - We show, using superconducting tunneling spectroscopy and tunneling
      magnetoresistance measurements, that ferrimagnetic alloys of Co and Gd can
      exhibit both positive and negative spin polarization depending on temperature and
      composition. These observations can be understood by considering the relative
      contributions of independent spin-polarized tunneling currents from the rare
      earth-metal and transition-metal subnetwork magnetizations, which are coupled
      antiferromagnetically. At the compensation point of the alloy, where the
      subnetwork magnetizations are equal and the alloy has nearly zero net
      magnetization, nevertheless large tunneling spin polarization is observed.

PMID- 16090837
TI  - Magnetic density of states at low energy in geometrically frustrated systems.
AB  - Using muon-spin-relaxation measurements we show that the pyrochlore compound
      Gd(2)Ti(2)O(7), in its magnetically ordered phase below approximately 1 K,
      displays persistent spin dynamics down to temperatures as low as 20 mK. The
      characteristics of the induced muon relaxation can be accounted for by a
      scattering process involving two magnetic excitations, with a density of states
      characterized by an upturn at low energy and a small gap depending linearly on
      the temperature. We propose that such a density of states is a generic feature of
      geometrically frustrated magnetic materials.

PMID- 16090838
TI  - Optical high harmonic generation in C60.
AB  - High harmonic generation (HHG) requires a strong laser field, but in C60 a
      relatively weak laser field is sufficient. Numerical results presented here show
      that, while its low order harmonics result from the laser field, its high order
      ones are mainly from the multiple excitations. Since high order harmonics
      directly correlate with electronic transitions, the HHG spectrum accurately
      measures transition energies. Therefore, C60 is not only a promising material for
      HHG, but may also present an opportunity to develop HHG into an electronic
      structure probing tool.

PMID- 16090839
TI  - Femtosecond photomagnetic switching of spins in ferrimagnetic garnet films.
AB  - We demonstrate that intense laser pulses can be used to directly control the
      spins in ferrimagnetic garnet films. Through an ultrafast and nonthermal
      photomagnetic effect the magnetocrystalline anisotropy is modified to create a
      new long-lived equilibrium orientation for the magnetization. Simultaneously, the
      magnetization is rotated into this new state by precession in a strong transient
      optically generated magnetic field. All take place within the 100 fs duration of
      a single laser pulse, thus demonstrating the feasibility of photomagnetic
      switching on the femtosecond time scale.

PMID- 16090840
TI  - Geometrical effects on the optical properties of quantum dots doped with a single
      magnetic atom.
AB  - The emission spectra of individual self-assembled quantum dots containing a
      single magnetic Mn atom differ strongly from dot to dot. The differences are
      explained by the influence of the system geometry, specifically the in-plane
      asymmetry of the quantum dot and the position of the Mn atom. Depending on both
      these parameters, one has different characteristic emission features which either
      reveal or hide the spin state of the magnetic atom. The observed behavior in both
      zero field and under magnetic field can be explained quantitatively by the
      interplay between the exciton-manganese exchange interaction (dependent on the Mn
      position) and the anisotropic part of the electron-hole exchange interaction
      (related to the asymmetry of the quantum dot).

PMID- 16090841
TI  - Photoemission electron microscopy as a tool for the investigation of optical near
      fields.
AB  - Photoemission electron microscopy was used to image the electrons photoemitted
      from specially tailored Ag nanoparticles deposited on a Si substrate (with its
      native oxide SiO(x)). Photoemission was induced by illumination with a Hg UV lamp
      (photon energy cutoff homega(UV) = 5.0 eV, wavelength lambda(UV) = 250 nm) and
      with a Ti:sapphire femtosecond laser (homega(l) = 3.1 eV, lambda(l) = 400 nm,
      pulse width below 200 fs), respectively. While homogeneous photoelectron emission
      from the metal is observed upon illumination at energies above the silver plasmon
      frequency, at lower photon energies the emission is localized at tips of the
      structure. This is interpreted as a signature of the local electrical field
      therefore providing a tool to map the optical near field with the resolution of
      emission electron microscopy.

PMID- 16090842
TI  - Surface-assisted monodomain formation of an ordered phase of soft matter via the
      first-order phase transition.
AB  - We produced a monodomain ordered structure with the help of a surface-mediated
      first-order transition, using a sponge-to-lamella transition in a membrane
      suspension as a model system. The long characteristic length and time scales of
      the system allow us to observe the process of the phase ordering in a confined
      geometry with optical microscopy in real time. We demonstrate that a
      homogeneously ordered domain can be attained if we prevent nucleation in bulk by
      using its kinetic coupling to nucleation on the surface.

PMID- 16090843
TI  - Axial segregation of a settling suspension in a rotating cylinder.
AB  - A rotating suspension of nonbuoyant particles can develop striking
      inhomogeneities in particle concentration, with regular bands of high and low
      concentration along the symmetry axis. We report Stokes-flow simulations showing
      that the formation of axial bands is correlated with an inhomogeneous particle
      distribution in the radial plane. An order parameter, based on the average
      angular velocity of the particles, characterizes two distinct phases: a low
      frequency segregated phase and a high-frequency dispersed phase. The axial band
      structure develops during the transition between these two phases.

PMID- 16090844
TI  - Electrostatically driven spatial patterns in lipid membrane composition.
AB  - To explore the physical mechanisms that can guide spatial organization at
      biological membranes, we have constructed simple, cell-free intermembrane
      junctions. We find that the mechanically driven patterning of proteins uncovered
      in our earlier work can electrostatically generate spatial patterns in the
      distribution of charged membrane lipids. Tuning the magnitude of the interaction
      as a function of composition and ionic strength, and analyzing the interplay
      between thermodynamics and electrostatics via a Poisson-Boltzmann approach, we
      are able to determine the charge density and surface potential of the junction
      components. Surprisingly, the electrostatic potential of the proteins is a minor
      factor in the lipid reorganization; the protein size and its modulation of the
      junction topography play the dominant role in driving the electrostatic patterns.

PMID- 16090845
TI  - Mechanical shear can accelerate the gelation of actin filament networks.
AB  - Rearrangements of the filamentous actin cytoskeleton at the leading edge of
      motile cells occur under large mechanical stresses. Contrary to conventional
      wisdom, we show that mechanical deformations applied during gelation can
      accelerate the rate of gelation and produce F-actin networks that are stiffer and
      mechanically more resilient than those polymerized under low or high shear
      deformations. Above a threshold shear strain amplitude, F-actin networks collapse
      and become soft and liquidlike. This effect of shear-induced strengthening of
      polymerizing networks depends on the state of hydrolysis of the actin-bound
      adenosine triphosphate.

PMID- 16090847
TI  - Dynamics of critical Kauffman networks under asynchronous stochastic update.
AB  - We show that the mean number of attractors in a critical Boolean network under
      asynchronous stochastic update grows like a power law and that the mean size of
      the attractors increases as a stretched exponential with the system size. This is
      in strong contrast to the synchronous case, where the number of attractors grows
      faster than any power law.

PMID- 16090846
TI  - Time-dependent strength of colloidal gels.
AB  - Colloidal silica gels are shown to stiffen with time, as demonstrated by both
      dynamic light scattering and bulk rheological measurements. Their elastic moduli
      increase as a power law with time, independent of particle volume fraction;
      however, static light scattering indicates that there are no large-scale
      structural changes. We propose that increases in local elasticity arising from
      bonding between neighboring colloidal particles can account for the strengthening
      of the network, while preserving network structure.

PMID- 16090848
TI  - Comment on "measuring a photonic qubit without destroying it.

PMID- 16090850
TI  - Comment on "constraints on proton structure from precision atomic-physics
      measurements".

PMID- 16090852
TI  - Direct nondestructive imaging of magnetization in a spin-1 Bose-Einstein gas.
AB  - Polarization-dependent phase-contrast imaging is used to resolve the spatial
      magnetization profile of an optically trapped ultracold gas. This probe is
      applied to Larmor precession of degenerate and nondegenerate spin-1 87Rb gases.
      Transverse magnetization of the Bose-Einstein condensate persists for the
      condensate lifetime, with a spatial response to magnetic field inhomogeneities
      consistent with a mean-field model of interactions. In comparison, the
      magnetization of the non-condensed gas decoheres rapidly. Rotational symmetry
      implies that the Larmor frequency of a spinor condensate be density independent,
      and thus suitable for precise magnetometry with high spatial resolution.

PMID- 16090853
TI  - Large-N scaling behavior of the Lipkin-Meshkov-Glick model.
AB  - We introduce a novel semiclassical approach to the Lipkin model. In this way the
      well-known phase transition arising at the critical value of the coupling is
      intuitively understood. New results--showing for strong couplings the existence
      of a threshold energy which separates deformed from undeformed states as well as
      the divergence of the density of states at the threshold energy--are explained
      straightforwardly and in quantitative terms by the appearance of a double well
      structure in a classical system corresponding to the Lipkin model. Previously
      unnoticed features of the eigenstates near the threshold energy are also
      predicted and found to hold.

PMID- 16090854
TI  - Fully three dimensional breather solitons can be created using feshbach
      resonances.
AB  - We investigate the stability properties of breather solitons in a three
      dimensional Bose-Einstein condensate with Feshbach resonance management of the
      scattering length and confined only by a one-dimensional optical lattice. We
      compare regions of stability in parameter space obtained from a fully 3D analysis
      with those from a quasi-two-dimensional treatment. For moderate confinement we
      discover a new island of stability in the 3D case, not present in the quasi-2D
      treatment. Stable solutions from this region have non-trivial dynamics in the
      lattice direction; hence, they describe fully 3D breather solitons. We
      demonstrate these solutions in direct numerical simulations and outline a
      possible way of creating robust 3D solitons in experiments in a Bose-Einstein
      condensate in a one-dimensional lattice. We point out other possible
      applications.

PMID- 16090855
TI  - Phase coherence of an atomic Mott insulator.
AB  - We investigate the phase coherence properties of ultracold Bose gases in optical
      lattices, with special emphasis on the Mott insulating phase. We show that phase
      coherence on short length scales persists even deep in the insulating phase,
      preserving a finite visibility of the interference pattern observed after free
      expansion. This behavior can be attributed to a coherent admixture of particle
      hole pairs to the perfect Mott state for small but finite tunneling. In addition,
      small but reproducible kinks are seen in the visibility, in a broad range of atom
      numbers. We interpret them as signatures for density redistribution in the shell
      structure of the trapped Mott insulator.

PMID- 16090856
TI  - Uniform approximation for the coherent-state propagator using a conjugate
      application of the Bargmann representation.
AB  - We propose a conjugate application of the Bargmann representation of quantum
      mechanics. Applying the Maslov method to the semiclassical connection formula
      between the two representations, we derive a uniform semiclassical approximation
      for the coherent-state propagator which is finite at phase space caustics.

PMID- 16090857
TI  - Geometric phase in eigenspace evolution of invariant and adiabatic action
      operators.
AB  - The theory of geometric phase is generalized to a cyclic evolution of the
      eigenspace of an invariant operator with N-fold degeneracy. The corresponding
      geometric phase is interpreted as a holonomy inherited from the universal Stiefel
      U(N) bundle over a Grassmann manifold. Most significantly, for an arbitrary
      initial state, this holonomy captures the inherent geometric feature of the state
      evolution that may not be cyclic. Moreover, a rigorous theory of geometric phase
      in the evolution of the eigenspace of an adiabatic action operator is also
      formulated, with the corresponding holonomy being elaborated by a pullback U(N)
      bundle.

PMID- 16090858
TI  - Analytically solving the relativistic Dirac-Coulomb equation for atoms and
      molecules.
AB  - A method of solving the Schrodinger equation in an analytically expanded form
      reported previously is extended to the relativistic case and a general method of
      exactly solving the Dirac-Coulomb equation has been proposed for atoms and
      molecules. Some problems characteristic of the relativistic case are discussed.
      Test applications to the hydrogen-like, helium-like atoms are satisfactory,
      implying a high potentiality of the proposed method also for the relativistic
      case.

PMID- 16090859
TI  - Fast quantum algorithm for numerical gradient estimation.
AB  - Given a black box for f, a smooth real scalar function of d real variables, one
      wants to estimate [symbol: see text]f at a given point with n bits of precision.
      On a classical computer this requires a minimum of d + 1 black box queries,
      whereas on a quantum computer it requires only one query regardless of d. The
      number of bits of precision to which f must be evaluated matches the classical
      requirement in the limit of large n.

PMID- 16090860
TI  - Strong hyperon-nucleon pairing in neutron stars.
AB  - We explore the possibilities of hyperon-nucleon pairing, involving lambda or
      sigma- hyperons, using different Nijmegen hyperon-nucleon potentials. We find
      possible very large nsigma- gaps and estimate their relevance for neutron star
      physics.

PMID- 16090861
TI  - Exact quantization of Einstein-Rosen waves coupled to massless scalar matter.
AB  - We show in this Letter that gravity coupled to a massless scalar field with full
      cylindrical symmetry can be exactly quantized by an extension of the techniques
      used in the quantization of Einstein-Rosen waves. This system provides a useful
      test bed to discuss a number of issues in quantum general relativity, such as the
      emergence of the classical metric, microcausality, and large quantum gravity
      effects. It may also provide an appropriate framework to study gravitational
      critical phenomena from a quantum point of view, issues related to black hole
      evaporation, and the consistent definition of test fields and particles in
      quantum gravity.

PMID- 16090862
TI  - Kertesz line in the three-dimensional compact U(1) lattice Higgs model.
AB  - The three-dimensional lattice Higgs model with compact U(1) gauge symmetry and
      unit charge is investigated by means of Monte Carlo simulations. The full model
      with fluctuating Higgs amplitude is simulated, and both energy as well as
      topological observables are measured. The data show a Higgs and a confined phase
      separated by a well-defined phase boundary, which is argued to be caused by
      proliferating vortices. For fixed gauge coupling, the phase boundary consists of
      a line of first-order phase transitions at small Higgs self-coupling, ending at a
      critical point. The phase boundary then continues as a Kertesz line across which
      thermodynamic quantities are non-singular. Symmetry arguments are given to
      support these findings.

PMID- 16090865
TI  - Critical opacity: a possible explanation of the fast thermalization times seen in
      BNL RHIC experiments.
AB  - The Nambu-Jona-Lasinio Lagrangian offers an explication of the seemingly
      contradictory observations that (a) the energy loss in the entrance channel of
      heavy ion reactions is not sufficient to thermalize the system and that (b) the
      observed hadron cross sections are in almost perfect agreement with
      hydrodynamical calculations. According to this scenario, a critical opacity
      develops close to the chiral phase transition which equilibrates and hadronizes
      the expanding system very effectively. It creates as well radial flow and, if the
      system is not isotropic, finite upsilon2 values.

PMID- 16090866
TI  - Accurate determinations of alpha(s) from realistic lattice QCD.
AB  - We obtain a new value for the QCD coupling constant by combining lattice QCD
      simulations with experimental data for hadron masses. Our lattice analysis is the
      first to (1) include vacuum polarization effects from all three light-quark
      flavors (using MILC configurations), (2) include third-order terms in
      perturbation theory, (3) systematically estimate fourth and higher-order terms,
      (4) use an unambiguous lattice spacing, and (5) use an [symbol: see text](a2)
      accurate QCD action. We use 28 different (but related) short-distance quantities
      to obtain alpha((5)/(MS))(M(Z)) = 0.1170(12).

PMID- 16090868
TI  - Evidence for the two-pole structure of the lambda(1405) resonance.
AB  - The K- p --> pi0pi0sigma0 reaction is studied within a chiral unitary model. The
      distribution of pi0sigma0 states forming the lambda(1405) shows, in agreement
      with a recent experiment, a peak at 1420 MeV and a relatively narrow width of
      gamma = 38 MeV. The mechanism for the reaction is largely dominated by the
      emission of a pi0 prior to the K- p interaction leading to the lambda(1405). This
      ensures the coupling of the lambda(1405) to the K- p channel, thus maximizing the
      contribution of the second state found in chiral unitary theories, which is
      narrow and of higher energy than the nominal lambda(1405). This is unlike the pi-
      p --> K0pisigma reaction, which gives more weight to the pole at lower energy and
      with a larger width. The data of these two experiments, together with the present
      theoretical analysis, provide firm evidence of the two-pole structure of the
      lambda(1405).

PMID- 16090867
TI  - Measurement of the D(s)+ lifetime.
AB  - A high statistics measurement of the D(s)+ lifetime from the Fermilab fixed
      target FOCUS photoproduction experiment is presented. We describe the analysis of
      the two decay modes, D(s)+ --> phi(1020)pi+ and D(s)+ -->K*(892)0K+, used for the
      measurement. The measured lifetime is 507.4 +/- 5.5(stat) +/- 5.1(syst) fs using
      8961 +/- 105 D(s)+ --> phi(1020)pi+ and 4680 +/- 90 D(s)+ --> K*(892)0K+ decays.
      This is a significant improvement over the present world average.

PMID- 16090869
TI  - Spin-dependent structure functions in nuclear matter and the polarized EMC
      effect.
AB  - An excellent description of both spin-independent and spin-dependent quark
      distributions and structure functions has been obtained with a modified Nambu-
      Jona-Lasinio model, which is free of unphysical thresholds for nucleon decay into
      quarks--hence incorporating an important aspect of confinement. We utilize this
      model to investigate nuclear medium modifications to structure functions and find
      that we are readily able to reproduce both nuclear matter saturation and the
      experimental F2N(A)/F2N ratio, that is, the European Muon Collaboration (EMC)
      effect. Applying this framework to determine g1p(A), we find that the ratio
      g1p(A)/g1p differs significantly from unity, with the quenching caused by the
      nuclear medium being about twice that of the spin-independent case. This
      represents an exciting result, which, if confirmed experimentally, will reveal
      much about the quark structure of nuclear matter.

PMID- 16090870
TI  - Simultaneous measurement of beta- decay to bound and continuum electron states.
AB  - We report the first measurement of a ratio lambda(beta(b))/lambda(beta(c)) of
      bound-state ((lambda(beta(b))) and continuum-state (lambda(beta(c))) beta(-)
      decay rates for the case of bare 207Tl81+ ions. These ions were produced at the
      GSI fragment separator FRS by projectile fragmentation of a 208Pb beam. After in
      flight separation with the Brho-deltaE-Brho method, they were injected into the
      experimental storage-ring ESR at an energy of 400.5A MeV, stored, and electron
      cooled. The number of both the 207Tl81+ ions and their bound-state beta(-)-decay
      daughters, hydrogen-like 207Pb81+ ions, were measured as a function of storage
      time by recording their Schottky-noise intensities. The experimental result,
      lambda(beta(b))/lambda(beta(c)) = 0.188(18), is in very good agreement with the
      value of 0.171(1) obtained from theory employing spectra of allowed transitions.

PMID- 16090871
TI  - Interpretation of the processes 3He(e,e'p)2H and 3He(e,e'p)(pn) at high missing
      momenta.
AB  - Using realistic three-body wave functions corresponding to the AV18 interaction,
      it is shown that the effects of the final state interaction in the exclusive
      processes 3He(e,e'p)2H and 3He(e,e'p)(pn), can be successfully treated in terms
      of a generalized eikonal approximation based upon the direct calculation of the
      Feynman diagrams describing the rescattering of the struck nucleon. The relevant
      role played by the double rescattering contribution at high values of the missing
      momentum is illustrated.

PMID- 16090863
TI  - Search for Higgs bosons decaying into bb and produced in association with a
      vector boson in pp collisions at square root of s = 1.8 TeV.
AB  - We present a new search for H0V production, where H0 is a scalar Higgs boson
      decaying into bb with branching ratio beta, and V is a Z0 boson decaying into e+e
      , mu+mu-, or nunu. This search is then combined with previous searches for H0V
      where V is a W+/- boson or a hadronically decaying Z0. The data sample consists
      of 106 +/- 4 pb(-1) of pp collisions at square root of s = 1.8 TeV accumulated by
      the Collider Detector at Fermilab. Observing no evidence of a signal, we set 95%
      Bayesian credibility level upper limits on sigma(pp --> H0V) x beta. For H0
      masses of 90, 110, and 130 GeV/c2, the limits are 7.8, 7.2, and 6.6 pb,
      respectively.

PMID- 16090872
TI  - Dynamic supersymmetries of differential equations with applications to nuclear
      spectroscopy.
AB  - Dynamic supersymmetries of differential equations are defined. The case of a
      liquid drop with quadrupole deformation coupled to a particle with j = 3/2 is
      shown as an example of a situation where the dynamic supersymmetry OSp(5/4) may
      occur. A special solution, called E(5/4), of interest in the spectroscopy of odd
      even nuclei in the transitional region between spherical and gamma unstable is
      explicitly worked out.

PMID- 16090874
TI  - Fully relativistic theory of the ponderomotive force in an ultraintense standing
      wave.
AB  - A relativistic field-gradient (ponderomotive) force in a laser standing wave
      ceases to exist in a familiar form; e.g., the adiabatic Hamiltonian is not
      separable into kinetic and potential energies for electrons moving in the
      antinode planes. We show that the force in the direction across the initial
      motion of an electron reverses its sign and makes the high-field areas attractive
      for electrons, opposite to a regular ponderomotive force. The reversal occurs at
      a relativistic-scale incident momentum, and represents the only effect known so
      far that pins down a distinct borderline between relativistic and nonrelativistic
      motion.

PMID- 16090873
TI  - Magnetic trapping of ultracold Rydberg atoms.
AB  - We investigate the quantum dynamics of ultracold Rydberg atoms being exposed to a
      magnetic quadrupole field. A Hamiltonian describing the coupled dynamics of the
      electronic and center of mass motion is derived. Employing an adiabatic approach,
      the potential energy surfaces for intra-n-manifold mixing are computed. By
      determining the quantum states of the center of mass motion, we demonstrate that
      trapped states can be achieved if the total angular momentum of the atom is
      sufficiently large. This holds even if the extension of the electronic Rydberg
      state becomes equal to or even exceeds that of the ultracold center of mass
      motion.

PMID- 16090875
TI  - Enhancing the capacity and performance of collective atomic quantum memory.
AB  - Present schemes involving the quantum non-demolition interaction between atomic
      samples and off-resonant light pulses allow us to store quantum information
      corresponding to a single harmonic oscillator (mode) in one multi-atomic system.
      We discuss the possibility of involving several coherences of each atom so that
      the atomic sample can store information contained in several quantum modes. This
      is achieved by the coupling of different magnetic sublevels of the relevant
      hyperfine level by additional Raman pulses. This technique allows us to design
      not only the quantum non-demolition coupling, but also beam splitter-like and two
      mode squeezer-like interactions between light and collective atomic spin.

PMID- 16090876
TI  - Two dimensional counterpropagating spatial solitons in photorefractive crystals.
AB  - We demonstrate experimentally the existence of two transverse-dimensional
      counterpropagating (CP) incoherent spatial solitons in a 5 x 5 x 23 mm SBN:60Ce
      photorefractive crystal and investigate their dynamical behavior. We carry out
      numerical simulations that confirm our experimental findings. Substantially
      different behavior from the copropagating incoherent solitons is found. A
      symmetry breaking transition from stable overlapping CP solitons to unstable
      transversely displaced CP solitons is observed. We perform linear stability
      analysis that predicts the threshold for the split-up transition, in qualitative
      agreement with numerical simulations and experimental results.

PMID- 16090877
TI  - Discrete Talbot effect in waveguide arrays.
AB  - We report the first observation of discrete Talbot revivals in one-dimensional
      waveguide arrays. Unlike continuous systems where the Talbot self-imaging effect
      always occurs irrespective of the pattern period, in discrete configurations this
      process is only possible for a specific set of periodicities. Recurrence of
      different input periodic patterns is observed in good agreement with theory.

PMID- 16090878
TI  - Curvilinear motion of multivortex laser-soliton complexes with strong and weak
      coupling.
AB  - We reveal the existence of stable dissipative soliton complexes with curvilinear
      motion of their center of mass. This type of motion results from the field
      distribution asymmetry and is well pronounced for asymmetric complexes of laser
      solitons with strong coupling. We present results of numerical simulations of
      such complexes in a model of wide-aperture lasers or laser amplifiers with
      saturable gain and absorption. The complex consists of a pair of strongly coupled
      vortex solitons weakly coupled with a number of other vortex solitons. Similar
      complexes are expected to exist in different spatially distributed nonlinear
      dissipative systems, including schemes with discrete dissipative solitons.

PMID- 16090879
TI  - Observation of second-band vortex solitons in 2D photonic lattices.
AB  - We demonstrate second-band bright vortex-array solitons in photonic lattices.
      This constitutes the first experimental observation of higher-band solitons in
      any 2D periodic system. These solitons possess complex intensity and phase
      structures, yet they can be excited by a simple highly localized vortex-ring
      beam. Finally, we show that the linear diffraction of such beams exhibits
      preferential transport along the lattice axes.

PMID- 16090864
TI  - Study of Zgamma events and limits on anomalous ZZgamma and Zgammagamma couplings
      in pp collisions at square root s = 1.96 TeV.
AB  - We present a measurement of the Zgamma production cross section and limits on
      anomalous ZZgamma and Zgammagamma couplings for form-factor scales of lambda =
      750 and 1000 GeV. The measurement is based on 138 (152) candidates in the eegamma
      (mumugamma) final state using 320(290) pb(-1) of pp(-1) collisions at square root
      of s = 1.96 TeV. The 95% C.L. limits on real and imaginary parts of individual
      anomalous couplings are /h(10,30)Z/ < 0.23, /h(20,40)Z/ < 0.020, /h(10,30)gamma/
      < 0.23, and /h(20,40)gamma/ < 0.019 for lambda = 1000 GeV.

PMID- 16090880
TI  - Observation of spontaneous self-channeling of light in air below the collapse
      threshold.
AB  - We report the observation of the self-guided propagation of 120 fs, 0.56 mJ
      infrared radiation in air for distances greater than 1 m. In contrast with the
      known case of filamentation, in the present experiment the laser power is lower
      than the collapse threshold. Therefore the counterbalance between Kerr self
      focusing and ionization induced defocusing as the stabilizing mechanism is ruled
      out. Instead, we find evidence of a process in which the transversal beam
      distribution reshapes into a form similar to a Townes soliton, with the
      particularity of a very high stability. We include numerical support for this
      conclusion.

PMID- 16090881
TI  - Conformation statistics of a deformable material line in two-dimensional
      turbulence.
AB  - We have observed the fluctuations of the centerline position of a thin column of
      water injected into a turbulent soap film. As the turbulence intensity increases,
      the second order structure function of the centerline position increments
      undergoes a change between different power law scaling regimes. These scalings
      indicate that the centerline position makes a continuous transition from an
      analytic to a non-analytic function. Cusps and other singular configurations of
      the column occur at higher turbulent intensities. Since the column supports
      random wave patterns, we propose that this experiment could serve as a test bed
      for theories of wave turbulence in one dimension.

PMID- 16090882
TI  - Observation of anomalously large spectral bandwidth in a high-gain self-amplified
      spontaneous emission free-electron laser.
AB  - Observation of ultrawide bandwidth, up to 15% full-width, high-gain operation of
      a self-amplified spontaneous emission free-election laser (SASE FEL) is reported.
      This type of lasing is obtained with a strongly chirped beam (deltaE/E
      approximately 1.7%) emitted from the accelerator. Because of nonlinear pulse
      compression during transport, a short, high current bunch with strong mismatch
      errors is injected into the undulator, giving high FEL gain. Start-to-end
      simulations reproduce key features of the measurements and provide insight into
      mechanisms, such as angular spread in emitted photon and electron trajectory
      distributions, which yield novel features in the radiation spectrum.

PMID- 16090883
TI  - Multi-GeV energy gain in a plasma-wakefield accelerator.
AB  - A plasma-wakefield accelerator has accelerated particles by over 2.7 GeV in a 10
      cm long plasma module. A 28.5 GeV electron beam with 1.8 x 10(10) electrons is
      compressed to 20 microm longitudinally and focused to a transverse spot size of
      10 microm at the entrance of a 10 cm long column of lithium vapor with density
      2.8 x 10(17) atoms/cm3. The electron bunch fully ionizes the lithium vapor to
      create a plasma and then expels the plasma electrons. These electrons return one
      half plasma period later driving a large amplitude plasma wake that in turn
      accelerates particles in the back of the bunch by more than 2.7 GeV.

PMID- 16090884
TI  - Experimental measurements of velocity dissipation and neutral-drag effects during
      the formation of a dusty plasma.
AB  - Stereoscopic particle image velocimety is used to make measurements of the
      formation of a dust cloud of 1.2 microm alumina particles in an argon dc glow
      discharge plasma. These measurements show a clear redistribution of particle
      velocities during the cloud formation process. Furthermore, these measurements
      suggest that the particle cloud reaches an equilibrium on a time scale over 100
      times slower than expected due to neutral-drag effects.

PMID- 16090885
TI  - Giant electron tails and passing electron pinch effects in tokamak-core
      turbulence.
AB  - The anomalous particle transport in a tokamak core is believed to be linked to
      the advection of magnetically trapped electrons alone, owing to the passing
      electrons maintaining a thermal equilibrium along the field lines. Surprisingly,
      in nonlinear numerical studies, the radial flux of passing electrons rivals that
      of the trapped ones. The strong interaction of passing electrons and electric
      fluctuations is mediated by long tails of the modes along the magnetic field,
      which are generated by the passing electrons in the first place.

PMID- 16090886
TI  - Experimental verification of the Hall effect during magnetic reconnection in a
      laboratory plasma.
AB  - In this Letter we report a clear and unambiguous observation of the out-of-plane
      quadrupole magnetic field suggested by numerical simulations in the reconnecting
      current sheet in the magnetic reconnection experiment. Measurements show that the
      Hall effect is large in the collision-less regime and becomes small as the
      collisionality increases, indicating that the Hall effect plays an important role
      in collision-less reconnection.

PMID- 16090887
TI  - Global minimum determination of the Born-Oppenheimer surface within density
      functional theory.
AB  - We present a novel method, which we refer to as the dual minima hopping method,
      that allows us to find the global minimum of the potential energy surface (PES)
      within density functional theory for systems where a fast but less accurate
      calculation of the PES is possible. This method can rapidly find the ground state
      configuration of clusters and other complex systems with present day computer
      power by performing a systematic search. We apply the new method to silicon
      clusters. Even though these systems have already been extensively studied by
      other methods, we find new global minimum candidates for Si16 and Si19, as well
      as new low-lying isomers for Si16, Si17, and Si18.

PMID- 16090888
TI  - Superfluid-insulator transition in a commensurate one-dimensional bosonic system
      with off-diagonal disorder.
AB  - We study the nature of the superfluid-insulator quantum phase transition in a one
      dimensional system of lattice bosons with off-diagonal disorder in the limit of a
      large integer filling factor. Monte Carlo simulations of two strongly disordered
      models show that the universality class of the transition in question is the same
      as that of the superfluid-Mott-insulator transition in a pure system. This result
      can be explained by disorder self-averaging in the superfluid phase and the
      applicability of the standard quantum hydrodynamic action. We also formulate the
      necessary conditions which should be satisfied by the stong-randomness
      universality class, if one exists.

PMID- 16090889
TI  - Glassy aging dynamics.
AB  - We present time-dependent dielectric loss data for various glass formers below
      the glass temperature. The observed aging dynamics is described using a modified
      Kohlrausch-Williams-Watts law taking into account the variation of the relaxation
      time during aging. It leads to values for the aging relaxation time and
      stretching exponent, fully consistent with the results from equilibrium
      measurements performed at higher temperatures. Irrespective of the dynamic
      process prevailing in the investigated frequency region, the aging dynamics is
      always determined by the structural relaxation process.

PMID- 16090890
TI  - Transient topographies of ion patterned Si(111).
AB  - The surface of high fluence ion-sputtered Si(111) was found to exhibit a rich
      variety of transient one- and two-dimensional topographies that may be exploited
      as tunable self-organized arrays of nanostructures. Such transient effects are
      only partially described by analytical models of sputter patterning. However, a
      discrete atom kinetic Monte Carlo simulation model incorporating curvature
      dependent sputtering and surface diffusion reproduces many aspects of the
      transient morphological evolution, and clarifies the minimal model of sputter
      patterning.

PMID- 16090891
TI  - Inelastic neutron scattering study of low energy excitations in polymer thin
      films.
AB  - We report inelastic neutron scattering measurements on polystyrene thin films in
      a glassy state in the meV region. We found in elastic scattering that the mean
      square displacement <u2> decreased with film thickness, and hence the
      corresponding force constant f increased. In inelastic and quasielastic
      scattering, we observed the so-called boson peak at around 1.5 meV and the
      picosecond fast process for the first time in thin films, both of which decreased
      in intensity with film thickness. These results were discussed in terms of the
      potential hardening due to the confinement of polymer chains and/or the
      interfacial dead layer.

PMID- 16090892
TI  - Surface rheology of two-dimensional percolating networks: Langmuir films of
      polymer pancakes.
AB  - We report surface rheological measurements on Langmuir films of submicron-sized
      polymer coils (pancakes). The dynamics of the sol phase is found to be governed
      by free volume as in the simplest percolation problem. The observed rheology of
      the percolated phase (gel-like) is compatible with predictions for compressed
      arrangements of highly deformed soft particles interacting through their contact
      interfaces.

PMID- 16090893
TI  - Kinetics of water-assisted single-walled carbon nanotube synthesis revealed by a
      time-evolution analysis.
AB  - Here we investigate the kinetics of water-assisted CVD (henceforth denoted as
      supergrowth CVD) by a quantitative time-evolution analysis based on a simple
      growth model. We found that the supergrowth can be well described by a model
      where the dynamics of the catalyst activity is treated similar to radioactive
      decay. An in-depth analysis based on this growth model revealed the kinetics of
      the supergrowth CVD, showing a scale relationship between the carbon source and
      water, and elucidated the role of water as a catalyst activity enhancer and
      preserver.

PMID- 16090894
TI  - Self-assembly of polymer-tethered nanorods.
AB  - We present results of molecular simulations that predict the phases formed by
      self-assembly of nanorods functionalized by a polymer "tether." Microphase
      separation of the immiscible tethers and rods coupled with the liquid crystal
      ordering of the rods induces the formation of a cubic phase, a smectic C phase, a
      tetragonally perforated lamellar phase, and a honeycomb phase; the latter two
      have been observed experimentally but have not been predicted. We also predict a
      new phase--a racemic mixture of hexagonally ordered chiral cylinders that self
      assemble from these achiral building blocks.

PMID- 16090895
TI  - Interaction-induced adiabatic cooling and antiferromagnetism of cold fermions in
      optical lattices.
AB  - We propose an interaction-induced cooling mechanism for two-component cold
      fermions in an optical lattice. It is based on an increase of the spin entropy
      upon localization, an analogue of the Pomeranchuk effect in liquid helium 3. We
      discuss its application to the experimental realization of the antiferromagnetic
      phase. We illustrate our arguments with dynamical mean-field theory calculations.

PMID- 16090896
TI  - Two-point versus multipartite entanglement in quantum phase transitions.
AB  - We analyze correlations between subsystems for an extended Hubbard model exactly
      solvable in one dimension, which exhibits a rich structure of quantum phase
      transitions (QPTs). The T = 0 phase diagram is exactly reproduced by studying
      singularities of single-site entanglement. It is shown how comparison of the
      latter quantity and quantum mutual information allows one to recognize whether
      two-point or shared quantum correlations are responsible for each of the
      occurring QPTs. The method works in principle for any number D of degrees of
      freedom per site. As a by-product, we are providing a benchmark for direct
      measures of bipartite entanglement; in particular, here we discuss the role of
      negativity at the transition.

PMID- 16090897
TI  - Origin of the anomalous absence of hydride formation by ZrPd2.
AB  - Intermetallic compounds based on hydrogen absorbing elements usually form stable
      hydrides. This is the case for PdZr2. Surprisingly, ZrPd2 does not absorb
      hydrogen although both compounds have the same crystal structure and satisfy the
      empirical geometrical criteria for hydride formation. Results of ab initio
      calculations reveal an unanticipated purely electronic origin. These results have
      implications in the search for new intermetallics for hydrogen storage.

PMID- 16090898
TI  - Generation of spin currents via Raman scattering.
AB  - We show theoretically that stimulated spin-flip Raman scattering can be used to
      inject spin currents in doped semiconductors with spin-split bands. A pure spin
      current, where oppositely oriented spins move in opposite directions, can be
      injected in zinc blende crystals and structures. The calculated spin current
      should be detectable by pump-probe optical spectroscopy and anomalous Hall effect
      measurement.

PMID- 16090899
TI  - Scaling and decoherence in the nonequilibrium Kondo model.
AB  - We study the Kondo effect in quantum dots in an out-of-equilibrium state due to
      an applied dc-voltage bias. Using the method of infinitesimal unitary
      transformations ("flow equations"), we develop a perturbative scaling picture
      that naturally contains both equilibrium coherence and nonequilibrium decoherence
      effects. This framework allows one to study the competition between Kondo effect
      and current-induced decoherence, and it establishes a large regime dominated by
      single-channel Kondo physics for asymmetrically coupled quantum dots.

PMID- 16090900
TI  - Full counting statistics of strongly non-ohmic transport through single
      molecules.
AB  - We study analytically the full counting statistics of charge transport through
      single molecules, strongly coupled to a weakly damped vibrational mode. The
      specifics of transport in this regime--a hierarchical sequence of avalanches of
      transferred charges, interrupted by "quiet" periods--make the counting statistics
      strongly non-Gaussian. We support our findings for the counting statistics as
      well as for the frequency-dependent noise power by numerical simulations, finding
      excellent agreement.

PMID- 16090901
TI  - Electrical readout of the local nuclear polarization in the quantum Hall effect:
      a hyperfine battery.
AB  - It is demonstrated that the now well-established "flip-flop" mechanism of spin
      exchange between electrons and nuclei in the quantum Hall effect can be reversed.
      We use a sample geometry which utilizes separately contacted edge states to
      establish a local nuclear spin polarization--close to the maximum value
      achievable--by driving a current between electron states of different spin
      orientation. When the externally applied current is switched off, the sample
      exhibits an output voltage of up to a few tenths of a mV, which decays with a
      time constant typical for the nuclear spin relaxation. The surprising fact that a
      sample with a local nuclear spin polarization can act as a source of energy and
      that this energy is well above the nuclear Zeeman splitting is explained by a
      simple model which takes into account the effect of a local Overhauser shift on
      the edge state reconstruction.

PMID- 16090902
TI  - Electrical pump-and-probe study of spin singlet-triplet relaxation in a quantum
      dot.
AB  - Spin relaxation from a triplet excited state to a singlet ground state in a
      semiconductor quantum dot is studied by employing an electrical pump-and-probe
      method. Spin relaxation occurs via co-tunneling when the tunneling rate is
      relatively large, confirmed by a characteristic square dependence of the
      relaxation rate on the tunneling rate. When co-tunneling is suppressed by
      reducing the tunneling rate, the intrinsic spin relaxation is dominated by spin
      orbit interaction. We discuss a selection rule of the spin-orbit interaction
      based on the observed double-exponential decay of the triplet state.

PMID- 16090903
TI  - Dynamical coulomb blockade of multiple Andreev reflections.
AB  - We analyze the dynamical Coulomb blockade of multiple Andreev reflections (MAR)
      in a superconducting quantum point contact coupled to a macroscopic impedance. We
      find that at very low transmission the blockade scales as n2 with n =
      Int(2delta/eV), where V is the bias voltage and delta is the superconducting gap,
      as it would correspond to the occurrence of shots of charge ne. For higher
      transmission the blockade is reduced because of both the Pauli principle and the
      elastic renormalization of the MAR probability, and for certain voltage regions
      it may even become an anti-blockade; i.e., the current is enhanced due to the
      coupling with the electromagnetic environment.

PMID- 16090904
TI  - Electronic structure of metal-semiconductor nanojunctions in gold CdSe
      nanodumbbells.
AB  - The electronic properties of metal-semiconductor nanojunctions are investigated
      by scanning tunneling spectroscopy of gold-tipped CdSe rods. A gap similar to
      that in bare CdSe nanorods is observed near the nanodumbbell center, while subgap
      structure emerges near the metal-semiconductor nanocontact. This behavior is
      attributed to the formation of subgap interface states that vanish rapidly
      towards the center of the rod, consistent with theoretical predictions. These
      states lead also to modified Coulomb staircase, and in some cases to negative
      differential conductance, on the gold tips.

PMID- 16090905
TI  - Ehrenfest-time dependence of weak localization in open quantum dots.
AB  - Semiclassical theory predicts that the weak localization correction to the
      conductance of a ballistic chaotic cavity is suppressed if the Ehrenfest time
      exceeds the dwell time in the cavity [I. L. Aleiner and A. I. Larkin, Phys. Rev.
      B 54, 14423 (1996)]. We report numerical simulations of weak localization in the
      open quantum kicked rotator that confirm this prediction. Our results disagree
      with the "effective random matrix theory" of transport through ballistic chaotic
      cavities.

PMID- 16090906
TI  - Resonances in ferromagnetic gratings detected by microwave photoconductivity.
AB  - We investigate the impact of microwave excited spin excitations on the dc charge
      transport in a ferromagnetic (FM) grating. We observe both resonant and
      nonresonant microwave photoresistance, which are caused, respectively, by spin
      and charge dissipations of the microwave power into the FM. A macroscopic model
      based on Maxwell and Landau-Lifschitz equations reveals the mixing of spin and
      charge dissipations, which shows that the ferromagnetic anti-resonance is shifted
      when the conductivity is anisotropic. We find that the microwave
      photoconductivity provides a powerful new tool to study the interplay between
      photonic, spintronic, and charge effects in FM microstructures.

PMID- 16090907
TI  - Composite-fermion spin excitations as nu approaches 1/2: interactions in the
      Fermi sea.
AB  - Measurements of low-lying spin excitations by inelastic light scattering unveil a
      delicate balance between spin reversal and Fermi energies in the Fermi sea of
      composite fermions that emerges in the limit of nu --> 1/2. The interplays
      between these two fundamental quasiparticle interactions are uncovered in lowest
      spin-flip excitations in which the spin orientation and Landau level index of
      composite fermions change simultaneously. A collapse of the spin-flip excitation
      gap as nu --> 1/2 is linked to vanishing quasiparticle energy level spacings and
      loss of full spin polarization.

PMID- 16090908
TI  - New mean-field theory of the tt't''J model applied to high-T(c) superconductors.
AB  - We introduce a new mean-field approach to the tt't''J model that incorporates
      both electron-like quasiparticle and spinon excitations as suggested by some
      experiments and numerical studies. It leads to a mean-field phase diagram which
      is consistent with that of hole and electron doped cuprates. Moreover, it
      provides a framework to describe the observed evolution of the electron spectral
      function from the undoped insulator to the overdoped Fermi metal for both hole
      and electron doping. The theory also provides a new non-BCS mechanism leading to
      superconductivity.

PMID- 16090909
TI  - Superconductivity in disordered thin films: giant mesoscopic fluctuations.
AB  - We discuss the intrinsic inhomogeneities of superconductive properties of
      uniformly disordered thin films with a large dimensionless conductance g. It is
      shown that mesoscopic fluctuations, which usually contain a small factor 1/g, are
      crucially enhanced near the critical conductance g(cF) >> 1 where
      superconductivity is destroyed at T = 0 due to Coulomb suppression of the Cooper
      attraction. This leads to strong spatial fluctuations of the local transition
      temperature and thus to the percolative nature of the thermal superconductive
      transition.

PMID- 16090910
TI  - Gaplike excitations in the superconducting state of Bi2Sr2CaCu2O8 studied by
      resonant Raman scattering.
AB  - We report on the response of the electronic continuum from inelastic light
      scattering experiments over an extended energy range between 1.970 and 4.504 eV
      in the superconducting state of Bi2Sr2CaCu2O8. The formation of a substantial
      Raman feature at shifts below twice the superconducting gap as well as the
      additional weight above this energy are found to be strongly dependent on the
      incident photon energy. For excitation wavelengths observed in ultraviolet, we
      find an enhancement of the integrated spectral weight below T(c). The resulting
      composite feature shows three distinct resonances at 2.5, 3.3, and 3.8 eV. We
      strongly suggest that the superconductivity-induced changes are the result of
      both the opening of a superconducting gap and the appearance of a collective
      mode.

PMID- 16090911
TI  - Percolation transition in the heterogeneous vortex state of NbSe2.
AB  - A percolation transition in the vortex state of a superconducting 2H-NbSe2
      crystal is observed in the regime where vortices form a heterogeneous phase
      consisting of ordered and disordered domains. The transition is signaled by a
      sharp increase in critical current that occurs when the volume fraction of
      disordered domains reaches the value P(c) = 0.26 +/- 0.04. Measurements on
      different vortex states show that, while the temperature of the transition
      depends on history and measurement speed, the value of P(c) and the critical
      exponent characterizing the approach to it, r = 1.97 +/- 0.66, are universal.

PMID- 16090912
TI  - Coexistence of long-range order and spin fluctuation in geometrically frustrated
      clinoatacamite Cu2Cl(OH)3.
AB  - Muon spin rotation experiments are carried out on clinoatacamite, Cu2Cl(OH)3,
      which is a new geometrically frustrated system featuring a three-dimensional
      network of corner-sharing tetrahedral 3d Cu2+ spins. A long-range
      antiferromagnetic order occurs below 18.1 K with a surprisingly small entropy
      release of about 0.05Rln2/Cu. Below 6.5 K, the static long-range order transforms
      abruptly into a metastable state with nearly complete depolarization of muon
      spins which suggests strong fluctuation. The system then enters a state in which
      partial long-range order and spin fluctuation coexist down to the lowest
      experimentally attainable temperature of 20 mK. This work presents a novel system
      for studying geometric frustration.

PMID- 16090913
TI  - Neel-vector tunneling in antiferromagnetic molecular clusters.
AB  - From inelastic neutron scattering experiments, we demonstrate quantum tunneling
      of the Neel vector in the antiferromagnetic molecular ferric wheel CsFe8.
      Analysis of the linewidth of the tunneling transition evidences coherent
      tunneling.

PMID- 16090914
TI  - Spintronics of a nanoelectromechanical shuttle.
AB  - We consider effects of the spin degree of freedom on the nanomechanics of a
      single-electron transistor (SET) containing a nanometer-sized metallic cluster
      suspended between two magnetic leads. It is shown that in such a
      nanoelectromechanical SET (NEM-SET) the onset of an electromechanical instability
      leading to cluster vibrations and shuttle transport of electrons between the
      leads can be controlled by an external magnetic field. Different stable regimes
      of this spintronic NEM-SET operation are analyzed. Two different scenarios for
      the onset of shuttle vibrations are found.

PMID- 16090915
TI  - Origin of the asymmetric magnetization reversal behavior in exchange-biased
      systems: competing anisotropies.
AB  - The magnetization reversal in exchange-biased ferromagnetic-antiferromagnetic (FM
      AFM) bilayers is investigated. Different reversal pathways on each branch of the
      hysteresis loop, i.e., asymmetry, are obtained both experimentally and
      theoretically when the magnetic field is applied at certain angles from the
      anisotropy direction. The range of angles and the magnitude of this asymmetry are
      determined by the ratio between the FM anisotropy and the interfacial FM-AFM
      exchange anisotropy. The occurrence of asymmetry is linked with the appearance of
      irreversibility, i.e., finite coercivity, as well as with the maximum of exchange
      bias, increasing for larger anisotropy ratios. Our results indicate that
      asymmetric hysteresis loops are intrinsic to exchange-biased systems and the
      competition between anisotropies determines the asymmetric behavior of the
      magnetization reversal.

PMID- 16090916
TI  - Spin current and magnetoelectric effect in noncollinear magnets.
AB  - A new mechanism of the magnetoelectric effect based on the spin supercurrent is
      theoretically presented in terms of a microscopic electronic model for
      noncollinear magnets. The electric polarization P(ij) produced between the two
      magnetic moments S(i) and S(j) is given by P proportional e(ij) X (S(i) X S(j))
      with e(ij) being the unit vector connecting the sites i and j. Applications to
      the spiral spin structure and the gauge theoretical interpretation are discussed.

PMID- 16090917
TI  - Efficient evaluation of partition functions of inhomogeneous many-body spin
      systems.
AB  - We present a numerical method to evaluate partition functions and associated
      correlation functions of inhomogeneous 2D classical spin systems and 1D quantum
      spin systems. The method is scalable and has a controlled error. We illustrate
      the algorithm by calculating the finite-temperature properties of bosonic
      particles in 1D optical lattices, as realized in current experiments.

PMID- 16090918
TI  - Ultrafast all optical switching via tunable Fano interference.
AB  - Tunneling induced quantum interference experienced by an incident probe in
      asymmetric double quantum wells can easily be modulated by means of an external
      control light beam. This phenomenon, which is here examined within the dressed
      state picture, can be exploited to devise a novel all-optical ultrafast switch.
      For a suitably designed semiconductor heterostructure, the switch is found to
      exhibit frequency bandwidths of the order of 0.1 THz and response and recovery
      times of about 1 ps.

PMID- 16090919
TI  - In situ Brillouin spectroscopy of a pressure-induced apparent second-order
      transition in a silicate glass.
AB  - Brillouin scattering measurements of a silicate glass, carried out at high
      pressures in the diamond anvil cell, show a dramatic increase in the pressure
      dependence of longitudinal velocity, and a discontinuity in the compressibility
      of the glass at about 6 GPa. While a first-order phase transition has been
      documented under pressure within amorphous ice, we demonstrate that an apparent
      second-order transition to a new, structurally distinct amorphous phase can occur
      via the abrupt onset of a new compressional mechanism, which may be triggered by
      a shift in polymerization of the glass or an onset of a change in coordination of
      silicon, within pressurized amorphous silicates.

PMID- 16090920
TI  - Solenoids and plectonemes in stretched and twisted elastomeric filaments.
AB  - We study the behavior of a naturally straight highly extensible elastic filament
      subjected to large extensional and twisting strains. We find that two different
      phases can coexist for a range of parameter values: the plectoneme and the
      solenoid. A simple theory based on a neo-Hookean model for the material of the
      filament and accounting for the slender geometry suffices to explain these
      observations, and leads to a phase diagram that is consistent with observations.
      Extension and relaxation experiments on these phases show the presence of large
      hysteresis loops and sawtooth-like force-displacement curves which are different
      for the plectoneme and the solenoid.

PMID- 16090921
TI  - Phase transition in a healthy human heart rate.
AB  - A healthy human heart rate displays complex fluctuations which share
      characteristics of physical systems in a critical state. We demonstrate that the
      human heart rate in healthy individuals undergoes a dramatic breakdown of
      criticality characteristics, reminiscent of continuous second order phase
      transitions. By studying the germane determinants, we show that the hallmark of
      criticality--highly correlated fluctuations--is observed only during usual daily
      activity, and a breakdown of these characteristics occurs in prolonged, strenuous
      exercise and sleep. This finding is the first reported discovery of the dynamical
      phase transition phenomenon in a biological control system and will be a key to
      understanding the heart rate control system in health and disease.

PMID- 16090922
TI  - Conformational transitions of nongrafted polymers near an absorbing substrate.
AB  - We have performed multi-canonical chain-growth simulations of a polymer
      interacting with an adsorbing surface. The polymer, which is not explicitly
      anchored at the surface, experiences a hierarchy of phase transitions between
      conformations binding and nonbinding with the substrate. We discuss the phase
      diagram in the temperature-solubility plane and highlight the transition path
      through the free-energy landscape.

PMID- 16090923
TI  - Transition state in a noisy environment.
AB  - Transition state theory overestimates reaction rates in solution because
      conventional dividing surfaces between reagents and products are crossed many
      times by the same reactive trajectory. We describe a recipe for constructing a
      time-dependent dividing surface free of such recrossings in the presence of
      noise. The no-recrossing limit of transition state theory thus becomes generally
      available for the description of reactions in a fluctuating environment.

PMID- 16090924
TI  - Wavelength halving in a transition between standing waves and traveling waves.
AB  - In the Belousov-Zhabotinsky reaction-diffusion system dispersed in a newly
      developed water-in-oil aerosol OT/Span-20 microemulsion, the transition between
      standing waves and traveling waves is accompanied by a halving of the wavelength.

PMID- 16090925
TI  - Comment on "Ambiguities in the up-quark mass".

PMID- 16090926
TI  - Efficient simulation of resistively shunted Josephson junctions.
AB  - We present a cluster algorithm for resistively shunted Josephson junctions or
      similar physical systems, which dramatically improves sampling efficiency, and
      apply it to the superconductor-to-metal transition in a single junction.
      Measuring the temperature dependence of the zero bias resistance, we confirm that
      the critical point does not depend on the strength of the Josephson coupling.
      However, we find that the correlation exponents vary continuously along the phase
      boundary, indicating that the Schmid-Bulgadaev transition is a line of fixed
      points.

PMID- 16090927
TI  - Finite-temperature quasicontinuum: molecular dynamics without all the atoms.
AB  - Using a combination of statistical mechanics and finite-element interpolation, we
      develop a coarse-grained (CG) alternative to molecular dynamics (MD) for
      crystalline solids at constant temperature. The new approach is significantly
      more efficient than MD and generalizes earlier work on the quasicontinuum method.
      The method is validated by recovering equilibrium properties of single crystal Ni
      as a function of temperature. CG dynamical simulations of nano-indentation reveal
      a strong dependence on temperature of the critical stress to nucleate
      dislocations under the indenter.

PMID- 16090928
TI  - Asymmetric two-component Fermion systems in strong coupling.
AB  - We study the phase structure of a dilute two-component Fermi system with
      attractive interactions as a function of the coupling and a finite number
      asymmetry or polarization. In weak coupling, a number asymmetry results in phase
      separation. A mixed phase containing symmetric superfluid matter and an
      asymmetric normal phase is favored. For strong coupling we show that the stress
      on the superfluid phase to accommodate a number asymmetry increases. Near the
      infinite-scattering length, we calculate the single-particle excitation spectrum
      and the ground-state energy. A picture of weakly interacting quasiparticles
      emerges for modest polarizations. In this regime a homogeneous phase with a
      finite population of quasiparticle states characterized by a gapless spectrum is
      favored over the phase separated state. These states may be realized in cold atom
      experiments.

PMID- 16090929
TI  - Formation of molecules near a Feshbach resonance in a 1D optical lattice.
AB  - We study the molecular behavior of two atoms interacting near a Feshbach
      resonance in the presence of a 1D periodic potential. The critical value of the
      scattering length needed to produce a molecule and the binding energy at
      resonance are calculated as a function of the intensity of the periodic
      potential. Because of the non-separability of the center of mass and relative
      motion, the binding energy depends on the quasimomentum of the molecule. This has
      dramatic consequences on the molecular tunneling properties, which become
      strongly dependent on the scattering length.

PMID- 16090930
TI  - Atomic Fermi gas in the trimerized kagome lattice at 2/3 filling.
AB  - We study low temperature properties of a spinless interacting Fermi gas in the
      trimerized kagome lattice. The case of two fermions per trimer is described by a
      quantum spin 1/2 model on the triangular lattice with couplings depending on the
      bond directions. Using exact diagonalizations we show that the system exhibits
      nonstandard properties of a quantum spin-liquid crystal, combining a planar
      antiferromagnetic order with an exceptionally large number of low-energy
      excitations.

PMID- 16090931
TI  - Approaching unit visibility for control of a superconducting qubit with
      dispersive readout.
AB  - In a Rabi oscillation experiment with a superconducting qubit we show that a
      visibility in the qubit excited state population of more than 95% can be
      attained. We perform a dispersive measurement of the qubit state by coupling the
      qubit non-resonantly to a transmission line resonator and probing the resonator
      transmission spectrum. The measurement process is well characterized and
      quantitatively understood. In a measurement of Ramsey fringes, the qubit
      coherence time is larger than 500 ns.

PMID- 16090932
TI  - Long-lived qubit memory using atomic ions.
AB  - We demonstrate experimentally a robust quantum memory using a magnetic-field
      independent hyperfine transition in 9Be+ atomic ion qubits at a magnetic field B
      approximately = 0.01194 T. We observe that the single physical qubit memory
      coherence time is greater than 10 s, an improvement of approximately 5 orders of
      magnitude from previous experiments with 9Be+. We also observe long coherence
      times of decoherence-free subspace logical qubits comprising two entangled
      physical qubits and discuss the merits of each type of qubit.

PMID- 16090933
TI  - Superbroadcasting of mixed states.
AB  - We derive the optimal universal broadcasting for mixed states of qubits. We show
      that the no-broadcasting theorem cannot be generalized to more than a single
      input copy. Moreover, for four or more input copies it is even possible to purify
      the input states while broadcasting. We name such purifying broadcasting
      superbroadcasting.

PMID- 16090934
TI  - Spatially compact solutions and stabilization in Einstein-Yang-Mills-Higgs
      theories.
AB  - New solutions to the static, spherically symmetric Einstein-Yang-Mills-Higgs
      equations with the Higgs field in the triplet (doublet) representation are
      presented. They form continuous families parametrized by alpha = M(W)/M(Pl) [M(W)
      (M(Pl)) denoting the W boson (the Planck) mass]. The corresponding space-times
      are regular and have spatially compact sections. A particularly interesting class
      with the Yang-Mills amplitude being nodeless is exhibited and is shown to be
      linearly stable with respect to spherically symmetric perturbations. For some
      solutions with nodes of the Yang-Mills amplitude a new stabilization phenomenon
      is found, according to which their unstable modes disappear as alpha increases
      (for the triplet) or decreases (for the doublet).

PMID- 16090935
TI  - Proper orthogonal decomposition of solar photospheric motions.
AB  - The spatiotemporal dynamics of the solar photosphere is studied by performing a
      proper orthogonal decomposition (POD) of line of sight velocity fields computed
      from high resolution data coming from the MDI/SOHO instrument. Using this
      technique, we are able to identify and characterize the different dynamical
      regimes acting in the system. Low-frequency oscillations, with frequencies in the
      range 20-130 microHz, dominate the most energetic POD modes (excluding solar
      rotation), and are characterized by spatial patterns with typical scales of about
      3 Mm. Patterns with larger typical scales of approximately 10 Mm, are associated
      to p-modes oscillations at frequencies of about 3000 microHz.

PMID- 16090936
TI  - Revealing the supernova-gamma-ray burst connection with TeV neutrinos.
AB  - Gamma-ray bursts (GRBs) are rare, powerful explosions displaying highly
      relativistic jets. It has been suggested that a significant fraction of the much
      more frequent core-collapse supernovae are accompanied by comparably energetic
      but mildly relativistic jets, which would indicate an underlying supernova-GRB
      connection. We calculate the neutrino spectra from the decays of pions and kaons
      produced in jets in supernovae, and show that the kaon contribution is dominant
      and provides a sharp break near 20 TeV, which is a sensitive probe of the
      conditions inside the jet. For a supernova at 10 Mpc, 30 events above 100 GeV are
      expected in a 10 s burst in the IceCube detector.

PMID- 16090937
TI  - Nonsingular black holes and degrees of freedom in quantum gravity.
AB  - Spherically symmetric space-times provide many examples for interesting black
      hole solutions, which classically are all singular. Following a general program,
      space-like singularities in spherically symmetric quantum geometry, as well as
      other inhomogeneous models, are shown to be absent. Moreover, one sees how the
      classical reduction from infinitely many kinematical degrees of freedom to only
      one physical one, the mass, can arise, where aspects of quantum cosmology such as
      the problem of initial conditions play a role.

PMID- 16090938
TI  - Measurement of time-dependent CP-violating asymmetries in B0 --> K(s)0K(s)0K(s)0
      decay.
AB  - We present a measurement of CP-violation parameters in the B0 --> K(s)0K(s)0K(s)0
      decay based on a sample of 275 x 10(6) BB pairs collected at the upsilon(4S)
      resonance with the Belle detector at the KEKB energy-asymmetric e+e- collider.
      One neutral B meson is fully reconstructed in the decay B0 --> K(s)0K(s)0K(s)0,
      and the flavor of the accompanying B meson is identified from its decay products.
      CP-violation parameters are obtained from the asymmetry in the distributions of
      the proper-time interval between the two B decays: S = +1.26 +/- 0.68(stat) +/-
      0.20(syst) and [symbol: see text] = +0.54 +/- 0.34(stat) +/- 0.09(syst).

PMID- 16090939
TI  - Observation of B+ --> plambdagamma.
AB  - We report the first observation of the radiative hyperonic B decay B+ -->
      plambdagamma, using a 140 fb(-1) data sample recorded on upsilom(4S) resonance
      with the Belle detector at the KEKB asymmetric energy e+e- collider. The measured
      branching fraction is [symbol: see text](B+ --> plambdagamma) = (2.16(+0.58)(
      0.53) +/- 0.20) x 10(-6). We examine its M(plambda) distribution and observe a
      peak near threshold. This feature is expected by the short-distance b --> sgamma
      transition. A search for B+ --> pepsilon0gamma yields no significant signal, and
      we set a 90% confidence-level upper limit on the branching fraction of [symbol:
      see textB+ --> pepsilon0gamma <4.6 x 10(-6).

PMID- 16090942
TI  - Decay of 1+ states as a new probe of the structure of 0+ shape isomers.
AB  - The nuclides 98Mo and 100Mo have been studied in photon-scattering experiments by
      using bremsstrahlung produced from electron beams with kinetic energies from 3.2
      to 3.8 MeV. Six electromagnetic dipole transitions in 98Mo and 19 in 100Mo were
      observed for the first time in the energy range from 2 to 4 MeV. A specific
      feature in the two nuclides is the de-excitation of one state with spin J = 1 to
      the 0+ ground state as well as to the first excited 0+ state, which cannot be
      explained in standard models. We present a model that allows us to deduce the
      mixing coefficients for the two 0+ shape-isomeric states from the experimental
      ratio of the transition strengths from the J = 1 state to the 0+ ground state and
      to the 0+ excited state.

PMID- 16090940
TI  - Observation of thirteen new exclusive multibody hadronic decays of the psi(2S).
AB  - Using data accumulated with the CLEO detector corresponding to an integrated
      luminosity of [symbol: see text] = 5.63 pb(-1) on the peak of the psi(2S) [3.08 x
      10(6) psi(2S) decays] and 20.70 pb(-1) at square root of[s] = 3.67 GeV, we report
      first measurements of the branching fractions for the following 13 decay modes of
      the psi(2S): eta3pi, &eta'3pi, rhoK+K-, K+K-pi+pi-pi0, 2(K+K-), 2(K+K-)pi0,
      rhopp, pppi+pi-pi0, etapp, ppK+K-, lambdalambdapi+pi-, lambdapK+, and
      lambdapK+pi+pi-, and more precise measurements of 8 previously measured modes:
      2(pi+pi-), rhopi+pi-, 2(pi+pi-)pi0, omegapi+pi-, K+K-pi+pi-, omegaK+K-, phiK+K-,
      and pppi+pi-. We also report new branching fraction measurements of phipi+pi- and
      omegapp and upper limits for etapi+pi-, etaK+K-, and phivpp. Results are
      compared, where possible, with the corresponding J/psi branching ratios to
      provide new tests of the 12% rule.

PMID- 16090943
TI  - Control of ultracold collisions with frequency-chirped light.
AB  - We report on ultracold atomic collision experiments utilizing frequency-chirped
      laser light. A rapid chirp below the atomic resonance results in adiabatic
      excitation to an attractive molecular potential over a wide range of internuclear
      separation. This leads to a transient inelastic collision rate which is large
      compared to that obtained with fixed-frequency excitation. The combination of
      high efficiency and temporal control demonstrates the benefit of applying the
      techniques of coherent control to the ultracold domain.

PMID- 16090944
TI  - Matter wave diffraction from an inclined transmission grating: searching for the
      elusive 4He trimer Efimov state.
AB  - The size of the helium trimer is determined by diffracting a beam of 4He clusters
      from a 100 nm period grating inclined by 21 degrees. Because of the bar thickness
      the projected slit width is roughly halved to 27 nm, increasing the sensitivity
      to the trimer size. The peak intensities measured out to the eighth order are
      evaluated via a few-body scattering theory. The trimer pair distance is found to
      be (r) = 1.1(+0.4)(-0.5) nm in agreement with predictions for the ground state.
      No evidence for a significant amount of Efimov trimers is found. Their
      concentration is estimated to be under 6%, less than expected.

PMID- 16090945
TI  - Measuring the quantum efficiency of the optical emission of single radiating
      dipoles using a scanning mirror.
AB  - Using scanning probe techniques, we show the controlled manipulation of the
      radiation from single dipoles. In one experiment we study the modification of the
      fluorescence lifetime of a single molecular dipole in front of a movable silver
      mirror. A second experiment demonstrates the changing plasmon spectrum of a gold
      nanoparticle in front of a dielectric mirror. Comparison of our data with
      theoretical models allows determination of the quantum efficiency of each
      radiating dipole.

PMID- 16090946
TI  - Tunable atomic magnetometer for detection of radio-frequency magnetic fields.
AB  - We describe an alkali-metal magnetometer for detection of weak magnetic fields in
      the radio-frequency (rf) range. High sensitivity is achieved by tuning the Zeeman
      resonance of alkali atoms to the rf frequency and partially suppressing spin
      exchange collisions in the alkali-metal vapor. We demonstrate magnetic field
      sensitivity of 2 fT/Hz(1/2) at a frequency of 99 kHz with a resonance width of
      400 Hz. We also derive a simple analytic expression for the fundamental limit on
      the sensitivity of the rf magnetometer and show that a sensitivity of about 0.01
      fT/Hz(1/2) can be achieved in a practical system with a measurement volume of 200
      cm3.

PMID- 16090947
TI  - Field-free two-direction alignment alternation of linear molecules by elliptic
      laser pulses.
AB  - We show that a linear molecule subjected to a short specific elliptically
      polarized laser field yields post-pulse revivals exhibiting alignment
      alternatively located along the orthogonal axis and the major axis of the
      ellipse. The effect is experimentally demonstrated by measuring the optical Kerr
      effect along two different axes. The conditions ensuring an optimal field-free
      alternation of high alignments along both directions are derived.

PMID- 16090948
TI  - Quantum many particle systems in ring-shaped optical lattices.
AB  - In the present work we demonstrate how to realize a 1D closed optical lattice
      experimentally, including a tunable boundary phase twist. The latter may induce
      "persistent currents" visible by studying the atoms' momentum distribution. We
      show how important phenomena in 1D physics can be studied by physical realization
      of systems of trapped atoms in ring-shaped optical lattices. A mixture of bosonic
      and/or fermionic atoms can be loaded into the lattice, realizing a generic
      quantum system of many interacting particles.

PMID- 16090949
TI  - Atom-molecule dark states in a Bose-Einstein condensate.
AB  - We have created a dark quantum superposition state of a Rb Bose-Einstein
      condensate and a degenerate gas of Rb2 ground-state molecules in a specific
      rovibrational state using two-color photo-association. As a signature for the
      decoupling of this coherent atom-molecule gas from the light field, we observe a
      striking suppression of photo-association loss. In our experiment the maximal
      molecule population in the dark state is limited to about 100 Rb2 molecules due
      to laser induced decay. The experimental findings can be well described by a
      simple three mode model.

PMID- 16090950
TI  - Mapping the magic numbers in binary Lennard-Jones clusters.
AB  - Using a global optimization approach that directly searches for the composition
      of greatest stability, we have been able to find the particularly stable
      structures for binary Lennard-Jones clusters with up to 100 atoms for a range of
      Lennard-Jones parameters. In particular, we have shown that just having atoms of
      different sizes leads to a remarkable stabilization of polytetrahedral
      structures, including both polyicosahedral clusters and at larger sizes
      structures with disclination lines.

PMID- 16090941
TI  - Multiplicity and pseudorapidity distributions of photons in Au+Au collisions at
      square root of (S(NN)) = 62.4 GeV.
AB  - We present the first measurement of pseudorapidity distribution of photons in the
      region 2.3 < or = eta < or = 3.7 for different centralities in Au+Au collisions
      at square root of (S(NN)) = 62.4 GeV. We find that the photon yield scales with
      the number of participating nucleons at all collision centralities studied. The
      pseudorapidity distribution of photons, dominated by pi0 decays, has been
      compared to those of charged pions, photons, and inclusive charged particles from
      heavy-ion and nucleon-nucleon collisions at various energies. The photon
      production has been shown to be consistent with the energy and centrality
      independent limiting fragmentation scenario.

PMID- 16090951
TI  - Emission of thermally activated electrons from rare gas clusters irradiated with
      intense VUV light pulses from a free electron laser.
AB  - The ionization dynamics of Ar and Xe clusters irradiated with intense vacuum
      ultraviolet light from a free-electron laser is investigated using photoelectron
      spectroscopy. Clusters comprising between 70 and 900 atoms were irradiated with
      femtosecond pulses at 95 nm wavelength (approximately 13 eV photon energy) and a
      peak intensity of approximately 4 x 10(12) W/cm2. A broad thermal distribution of
      emitted electrons from clusters with a maximum kinetic energy up to 30-40 eV is
      observed. The observation of relatively low-energy photoelectrons is in good
      agreement with calculations using a time-dependent Thomas-Fermi model and gives
      experimental evidence of an outer ionization process of the clusters, due to
      delayed thermoelectronic emission.

PMID- 16090952
TI  - Stopped light with storage times greater than one second using
      electromagnetically induced transparency in a solid.
AB  - We report on the demonstration of light storage for times greater than a second
      in praseodymium doped Y2SiO5 using electromagnetically induced transparency. The
      long storage times were enabled by the long coherence times possible for the
      hyperfine transitions in this material. The use of a solid-state system also
      enabled operation with the probe and coupling beam counter-propagating, allowing
      easy separation of the two beams. The efficiency of the storage was low because
      of the low optical thickness of the sample; as is discussed, this deficiency
      should be easy to rectify.

PMID- 16090953
TI  - Experimental reconstruction of photon statistics without photon counting.
AB  - Experimental reconstructions of photon number distributions of both continuous
      wave and pulsed light beams are reported. Our scheme is based on on/off avalanche
      photo-detection assisted by maximum-likelihood estimation and does not involve
      photon counting. Reconstructions of the distribution for both semiclassical and
      quantum states of light are reported for single-mode as well as for multi-mode
      beams.

PMID- 16090954
TI  - Surface-plasmon-assisted guiding of broadband slow and subwavelength light in
      air.
AB  - A class of axially uniform waveguides is introduced, employing a new mechanism to
      guide light inside a low-index dielectric material without the use of photonic
      band gap, and simultaneously exhibiting subwavelength modal size and very slow
      group velocity over an unusually large frequency bandwidth. Their basis is the
      presence of plasmonic modes on the interfaces between dielectric regions and the
      flat unpatterned surface of a bulk metallic substrate. These novel waveguides
      allow for easy broadband coupling and exhibit absorption losses limited only by
      the intrinsic loss of the metal.

PMID- 16090955
TI  - Slow light and superluminality in Kerr media without a pump.
AB  - Subluminal and superluminal propagation of a light pulse in Kerr materials has
      been investigated. Group velocities as slow as much less than 1 mm per second to
      as fast as negative several thousands meters per second can easily be obtained in
      the Kerr medium, which possesses a large nonlinear refractive index and long
      relaxation time, such as Cr3+-doped alexandrite, ruby, and GdAlO3. The physical
      mechanism is the strong highly dispersive coupling between different frequency
      components of the pulse.

PMID- 16090956
TI  - Low-frequency noise controls on-off intermittency of bifurcating systems.
AB  - A bifurcating system subject to multiplicative noise can display on-off
      intermittency. Using a canonical example, we investigate the extreme sensitivity
      of the intermittent behavior to the nature of the noise. Through a perturbative
      expansion and numerical studies of the probability density function of the
      unstable mode, we show that intermittency is controlled by the ratio between the
      departure from onset and the value of the noise spectrum at zero frequency.
      Reducing the noise spectrum at zero frequency shrinks the intermittency regime
      drastically. This effect also modifies the distribution of the duration that the
      system spends in the off phase. Mechanisms and applications to more complex
      bifurcating systems are discussed.

PMID- 16090957
TI  - q-Breathers and the Fermi-Pasta-Ulam problem.
AB  - The Fermi-Pasta-Ulam (FPU) paradox consists of the non-equipartition of energy
      among normal modes of a weakly anharmonic atomic chain model. In the harmonic
      limit each normal mode corresponds to a periodic orbit in phase space and is
      characterized by its wave number q. We continue normal modes from the harmonic
      limit into the FPU parameter regime and obtain persistence of these periodic
      orbits, termed here q-breathers (QB). They are characterized by time periodicity,
      exponential localization in the q-space of normal modes and linear stability up
      to a size-dependent threshold amplitude. Trajectories computed in the original
      FPU setting are perturbations around these exact QB solutions. The QB concept is
      applicable to other nonlinear lattices as well.

PMID- 16090958
TI  - Intermittency of velocity time increments in turbulence.
AB  - We analyze the statistics of turbulent velocity fluctuations in the time domain.
      Three cases are computed numerically and compared: (i) the time traces of
      Lagrangian fluid particles in a (3D) turbulent flow (referred to as the dynamic
      case); (ii) the time evolution of tracers advected by a frozen turbulent field
      (the static case); (iii) the evolution in time of the velocity recorded at a
      fixed location in an evolving Eulerian velocity field, as it would be measured by
      a local probe (referred to as the virtual probe case). We observe that the static
      case and the virtual probe cases share many properties with Eulerian velocity
      statistics. The dynamic (Lagrangian) case is clearly different; it bears the
      signature of the global dynamics of the flow.

PMID- 16090959
TI  - Nonlinear saturation of tearing mode islands.
AB  - New, rigorous results for the tearing island saturation problem are presented.
      These results are valid for the realistic case where the magnetic island
      structure is non-symmetric about the reconnection surface and the electron
      temperature, on which the electrical resistivity depends, is evolved self
      consistently with the island growth.

PMID- 16090960
TI  - Drift-kinetic Alfven waves observed near a reconnection X line in the earth's
      magnetopause.
AB  - We identify drift-kinetic Alfven waves in the vicinity of a reconnection X line
      on the Earth's magnetopause. The dispersive properties of these waves have been
      determined using wavelet interferometric techniques applied to multipoint
      observations from the Cluster spacecraft. Comparison of the observed wave
      dispersion with that expected for drift-kinetic Alfven waves shows close
      agreement. The waves propagate outwards from the X line suggesting that
      reconnection is a kinetic Alfven wave source. Energetic O+ ions observed in these
      waves indicate that reconnection is a driver of auroral ion outflow.

PMID- 16090961
TI  - Electronic transport in fullerene C20 bridge assisted by molecular vibrations.
AB  - The effect of molecular vibrations on electronic transport is investigated with
      the smallest fullerene C20 bridge, utilizing the Keldysh nonequilibrium Green's
      function techniques combined with the tight-binding molecular-dynamics method.
      Large discontinuous steps appear in the differential conductance when the applied
      bias voltage matches particular vibrational energies. The magnitude of the step
      is found to vary considerably with the vibrational mode and to depend on the
      local electronic states besides the strength of electron-vibration coupling. On
      the basis of this finding, a novel way to control the molecular motion by
      adjusting the gate voltage is proposed.

PMID- 16090962
TI  - Measuring the thermal conductivity of a single carbon nanotube.
AB  - Although the thermal properties of millimeter-sized carbon nanotube mats and
      packed carbon nanofibers have been readily measured, measurements for a single
      nanotube are extremely difficult. Here, we report a novel method that can
      reliably measure the thermal conductivity of a single carbon nanotube using a
      suspended sample-attached T-type nanosensor. Our experimental results show that
      the thermal conductivity of a carbon nanotube at room temperature increases as
      its diameter decreases, and exceeds 2000 W/mK for a diameter of 9.8 nm. The
      temperature dependence of the thermal conductivity for a carbon nanotube with a
      diameter of 16.1 nm appears to have an asymptote near 320 K. The present method
      is, in principle, applicable to any kind of a single nanofiber, nanowire, and
      even single-walled carbon nanotube.

PMID- 16090963
TI  - Control of the fragility of a glass-forming liquid using the liquid-liquid phase
      transition.
AB  - When a liquid approaches its glass-transition temperatures T(g), the structural
      relaxation time tau dramatically increases. This basic feature is ubiquitous, but
      this increase of tau can be classified between strong and fragile extremes using
      T(g) as a scaling parameter. Liquids, whose tau obeys the Arrhenius law, are
      called "strong," while "fragile" liquids have the super-Arrhenius behavior. Here
      we report the first continuous control of the fragility of liquid of the same
      material over a wide range of fragility, using a continuous liquid-liquid
      transition. Our study clearly demonstrates that the fragility is not a material
      specific quantity, but is controlled by the order parameter governing the liquid
      liquid transition, which may be the fraction of locally favored structures in the
      liquid.

PMID- 16090964
TI  - Brownian motion description of heat conduction by phonons.
AB  - A non-Markovian partial differential equation, rooted in the theory of Brownian
      motion, is proposed for describing heat conduction by phonons. Although a finite
      speed of propagation is a built-in feature of the equation, it does not give rise
      to an inauthentic wave front that results from the application of Cattaneo's
      equation. Even a simplified, analytically tractable version of the equation
      yields results close to those found by solving, through more elaborate means, the
      equation of phonon radiative transfer.

PMID- 16090965
TI  - Self-organization of gold atoms on a polar FeO(111) surface.
AB  - The spatial distribution of single Au atoms on a thin FeO film has been
      investigated by low-temperature scanning tunneling microscopy and spectroscopy.
      The adatoms preferentially adsorb on distinct sites of the Moire cell formed by
      the oxide layer and the Pt(111) support and arrange into a well-ordered hexagonal
      superlattice with 25 angstroms lattice constant. The self-organization is the
      consequence of an inhomogeneous surface potential within the FeO Moire cell and
      substantial electrostatic repulsion between the adatoms.

PMID- 16090966
TI  - Devil's staircase of incompressible electron states in a nanotube.
AB  - It is shown that a periodic potential applied to a nanotube can lock electrons
      into incompressible states. Depending on whether electrons are weakly or tightly
      bound to the potential, excitation gaps open up either due to the Bragg
      diffraction enhanced by the Tomonaga-Luttinger correlations, or via pinning of
      the Wigner crystal. Incompressible states can be detected in a Thouless pump
      setup, in which a slowly moving periodic potential induces quantized current,
      with a possibility to pump on average a fraction of an electron per cycle as a
      result of interactions.

PMID- 16090967
TI  - Mott transition and Kondo screening in f-electron metals.
AB  - We study how a finite hybridization between a narrow correlated band and a wide
      conduction band affects the Mott transition. At zero temperature, the
      hybridization is found to be a relevant perturbation, so that the Mott transition
      is suppressed by Kondo screening. In contrast, a first-order transition remains
      at finite temperature, separating a local-moment phase and a Kondo-screened
      phase. The first-order transition line terminates in two critical end points.
      Implications for experiments on f-electron materials such as the cerium alloy
      Ce0.8La0.1Th0.1 are discussed.

PMID- 16090968
TI  - Orbitronics: the intrinsic orbital current in p-doped silicon.
AB  - The spin Hall effect depends crucially on the intrinsic spin-orbit coupling of
      the energy band. Because of the smaller spin-orbit coupling in silicon, the spin
      Hall effect is expected to be much reduced. We show that an electric field in p
      doped silicon can induce a dissipationless orbital current in a fashion
      reminiscent of the spin Hall effect. The vertex correction from impurity
      scattering vanishes and the effect is robust against disorder. The orbital Hall
      effect leads to accumulation of local orbital momentum at the edge of the sample,
      and can be detected by the Kerr effect.

PMID- 16090969
TI  - Noise thermal impedance of a diffusive wire.
AB  - The current noise density S2 of a conductor in equilibrium, the Johnson noise, is
      determined by its temperature T: S2 = 4k(B)TG, with G the conductance. The
      sample's noise temperature T(N) = S2/(4k(B)G) generalizes T for a system out of
      equilibrium. We introduce the "noise thermal impedance" of a sample as the ratio
      deltaT(N)omega/deltaP(J)omega of the amplitude deltaT(N)omega of the oscillation
      of T(N) when heated by an oscillating power deltaP(J)omega at frequency omega.
      For a macroscopic sample, it is the usual thermal impedance. We show for a
      diffusive wire how this (complex) frequency-dependent quantity gives access to
      the electron-phonon interaction time in a long wire and to the diffusion time in
      a shorter one, and how its real part may also give access to the electron
      electron inelastic time. These times are not simply accessible from the frequency
      dependence of S2 itself.

PMID- 16090970
TI  - Zero-bias anomaly and kondo-assisted quasiballistic 2D transport.
AB  - Nonequilibrium transport measurements in mesoscopic quasiballistic 2D electron
      systems show an enhancement in the differential conductance around the Fermi
      energy. At very low temperatures, such a zero-bias anomaly splits, leading to a
      suppression of linear transport at low energies. We also observed a scaling of
      the nonequilibrium characteristics at low energies which resembles electron
      scattering by two-state systems, addressed in the framework of two-channel Kondo
      model. Detailed sample-to-sample reproducibility indicates an intrinsic
      phenomenon in unconfined 2D systems in the low electron-density regime.

PMID- 16090971
TI  - Observation of the Fano-Kondo antiresonance in a quantum wire with a side-coupled
      quantum dot.
AB  - We have observed the Fano-Kondo antiresonance in a quantum wire with a side
      coupled quantum dot. In a weak coupling regime, dips due to the Fano effect
      appeared. As the coupling strength increased, conductance in the regions between
      the dips decreased alternately. From the temperature dependence and the response
      to the magnetic field, we conclude that the conductance reduction is due to the
      Fano-Kondo antiresonance. At a Kondo valley with the Fano parameter q
      approximately 0, the phase shift is locked to pi/2 against the gate voltage when
      the system is close to the unitary limit in agreement with theoretical
      predictions by Gerland et al. [Phys. Rev. Lett. 84, 3710 (2000)].

PMID- 16090972
TI  - Percolating conduction in finite nanotube networks.
AB  - The percolating conductance of a new class of nanocomposite thin-film
      transistors, with channels composed of isotropic ensembles of nanotubes or
      nanowires, is analyzed as a function of wire/tube density and channel length. The
      conductance exponents are validated against analytical results for short channel
      transistors, and against available experimental data for longer channel devices.
      Our plots of conductance exponents as a function of tube-to-tube coupling
      strength provide a unified framework to interpret future experiments and should
      help design better nanocomposite transistors.

PMID- 16090973
TI  - Splitting of long-wavelength modes of the fractional quantum hall liquid at nu =
      1/3.
AB  - Resonant inelastic light scattering experiments at nu = 1/3 reveal a novel
      splitting of the long-wavelength modes in the low energy spectrum of quasi
      particle excitations in the charge degree of freedom. We find a single peak at
      small wave vectors that splits into two distinct modes at larger wave vectors.
      The evidence of well-defined dispersive behavior at small wave vectors indicates
      a coherence of the quantum fluid in the micron length scale. We evaluate
      interpretations of long-wavelength modes of the electron liquid.

PMID- 16090974
TI  - Manipulating nonequilibrium magnetism through superconductors.
AB  - Electrostatic control of the magnetization of a normal mesoscopic conductor is
      analyzed in a hybrid superconductor-normal-conductor-superconductor system. This
      effect stems from the interplay between the nonequilibrium condition in the
      normal region and the Zeeman splitting of the quasi-particle density of states of
      the superconductor subjected to a static in-plane magnetic field. Unexpected spin
      dependent effects such as magnetization suppression, diamagnetic-like response of
      the susceptibility, as well as spin-polarized current generation are the most
      remarkable features presented. The impact of scattering events is evaluated and
      lets us show that this effect is compatible with realistic material properties
      and fabrication techniques.

PMID- 16090975
TI  - Scattering of surface states at step edges in nanostripe arrays.
AB  - Surface states of noble metal surfaces split into Ag-like and Cu-like subbands in
      stepped Ag/Cu nanostripe arrays. The latter self-assemble by depositing Ag on
      vicinal Cu(111). Ag-like states scatter at nude step edges in Ag stripes, leading
      to umklapp bands, quantum size effects, and peak broadening. By contrast, Ag
      stripe boundaries become transparent to Cu-like states, which display band
      dispersion as in flat Cu(111). We find a linear relationship between the quantum
      size shift and peak broadening that applies in a variety of stepped systems,
      revealing the complex nature of step barrier potentials.

PMID- 16090976
TI  - Reduced electron relaxation rate in multielectron quantum dots.
AB  - We use a configuration-interaction approach and the Fermi golden rule to
      investigate electron-phonon interaction in multielectron quantum dots. Lifetimes
      are computed in the low-density, highly correlated regime. We report numerical
      evidence that electron-electron interaction generally leads to reduced decay
      rates of excited electronic states in weakly confined quantum dots, where carrier
      relaxation is dominated by the interaction with longitudinal acoustic phonons.

PMID- 16090977
TI  - Persistent spin currents without spin-orbit coupling in a spin-1/2 ring.
AB  - We show that a spatially dependent magnetic field can induce a persistent spin
      current in a spin-1/2 Heisenberg antiferromagnetic ring, proportional to the
      solid angle subtended by the magnetic field on a unit sphere. The magnitude of
      the spin current is determined by the ratio of longitudinal and transverse
      exchange interactions J(parallel)/J(perpendicular) and by the magnetic field
      magnitude.

PMID- 16090978
TI  - Quantization of the diagonal resistance: density gradients and the empirical
      resistance rule in a 2D system.
AB  - We have observed quantization of the diagonal resistance, R(xx), at the edges of
      several quantum Hall states. Each quantized R(xx) value is close to the
      difference between the two adjacent Hall plateaus in the off-diagonal resistance,
      R(xy). Peaks in R(xx) occur at different positions in positive and negative
      magnetic fields. Practically all R(xx) features can be explained quantitatively
      by a 1%/cm electron density gradient. Therefore, R(xx) is determined by R(xy) and
      unrelated to the diagonal resistivity rho(xx). Our findings throw an unexpected
      light on the empirical resistivity rule for 2D systems.

PMID- 16090979
TI  - Observation of quantum Hall "valley Skyrmions".
AB  - We report measurements of the interaction-induced quantum Hall effect in a spin
      polarized AlAs two-dimensional electron system where the electrons occupy two in
      plane conduction band valleys. Via the application of in-plane strain, we tune
      the energies of these valleys and measure the energy gap of the quantum Hall
      state at filling factor nu = 1. The gap has a finite value even at zero strain
      and, with strain, rises much faster than expected from a single-particle picture,
      suggesting that the lowest energy charged excitations at nu = 1 are "valley
      Skyrmions."

PMID- 16090980
TI  - Rabi-type oscillations in a classical Josephson junction.
AB  - We study analytically and numerically the phase-modulation properties of a
      classical Josephson tunnel junction biased in the zero-voltage state and phase
      locked to an external ac field. We show that the phase-locked state is being
      modulated in the transients, or in response to perturbations, and the modulation
      frequency is calculated as a function of relevant system parameters, such as
      microwave field amplitude. Our analysis demonstrates that the modulation of a
      phase-locked state in an entirely classical Josephson junction produces
      oscillations analogous to quantum mechanical Rabi oscillations, expected to be
      observed under the same conditions.

PMID- 16090981
TI  - Unpaired electrons in the heavy-fermion superconductor CeCoIn5.
AB  - Thermal conductivity and specific heat were measured in the superconducting state
      of the heavy-fermion material Ce(1-x)La(x)CoIn5. With increasing impurity
      concentration x, the suppression of T(c) is accompanied by the increase in
      residual electronic specific heat expected of a d-wave superconductor, but it
      occurs in parallel with a decrease in residual electronic thermal conductivity.
      This contrasting behavior reveals the presence of uncondensed electrons
      coexisting with nodal quasiparticles. An extreme multiband scenario is proposed,
      with a d-wave superconducting gap on the heavy-electron sheets of the Fermi
      surface and a negligible gap on the light, three-dimensional pockets.

PMID- 16090982
TI  - Magnetization reversal in submicron disks: exchange biased vortices.
AB  - Submicron, circular, ferromagnetic-antiferromagnetic dots exhibit different
      magnetization reversal mechanisms depending on the direction of the magnetic
      applied field. Shifted, constricted hysteresis loops, typical for vortex
      formation, are observed for fields along the exchange bias direction. However,
      for fields applied close to perpendicular to the exchange bias direction,
      magnetization reversal occurs via coherent rotation. Magnetic force microscopy
      imaging together with micromagnetic simulations are used to further clarify the
      different magnetic switching behaviors.

PMID- 16090983
TI  - Numerical renormalization-group study of the Bose-Fermi Kondo model.
AB  - We extend the numerical renormalization-group method to Bose-Fermi Kondo models
      (BFKMs), describing a local moment coupled to a conduction band and a dissipative
      bosonic bath. We apply the method to the Ising-symmetry BFKM with a bosonic bath
      spectral function eta(omega) proportional omega(s), of interest in connection
      with heavy-fermion criticality. For 0 < s < 1, an interacting critical point,
      characterized by hyperscaling of exponents and omega/T scaling, describes a
      quantum phase transition between Kondo-screened and localized phases. A
      connection is made to other results for the BFKM and the spin-boson model.

PMID- 16090984
TI  - Injection locking and phase control of spin transfer nano-oscillators.
AB  - We have directly measured phase locking of spin transfer oscillators to an
      injected ac current. The oscillators lock to signals up to several hundred
      megahertz away from their natural oscillation frequencies, depending on the
      relative strength of the input. As the dc current varies over the locking range,
      time-domain measurements show that the phase of the spin transfer oscillations
      varies over a range of approximately +/-90 degrees relative to the input. This is
      in good agreement with general theoretical analysis of injection locking of
      nonlinear oscillators.

PMID- 16090985
TI  - SU(4) Kondo effect in carbon nanotubes.
AB  - We investigate theoretically the nonequilibrium transport properties of carbon
      nanotube quantum dots. Owing to the two-dimensional band structure of graphene, a
      double orbital degeneracy plays the role of a pseudospin, which is entangled with
      the spin. Quantum fluctuations between these 4 degrees of freedom result in an
      SU(4) Kondo effect at low temperatures. This exotic Kondo effect manifests as a
      four-peak splitting in the nonlinear conductance when an axial magnetic field is
      applied.

PMID- 16090986
TI  - Local polarization fluctuations in an aging glass.
AB  - Polarization fluctuations were measured in nanoscale volumes of a polymer glass
      during aging following a temperature quench through the glass transition.
      Statistical properties of the noise were studied in equilibrium and during aging.
      The noise spectral density had a larger temporal variance during aging; i.e., the
      noise was more non-Gaussian, suggesting stronger correlations during aging.

PMID- 16090987
TI  - Exciton-photon strong-coupling regime for a single quantum dot embedded in a
      microcavity.
AB  - We report on the observation of the strong-coupling regime between the excitonic
      transition of a single GaAs quantum dot and a discrete optical mode of a
      microdisk microcavity. Photoluminescence is performed at various temperatures to
      tune the quantum dot exciton with respect to the optical mode. At resonance, we
      observe a clear anticrossing behavior, signature of the strong-coupling regime.
      The vacuum Rabi splitting amounts to 400 microeV and is twice as large as the
      individual linewidths.

PMID- 16090988
TI  - Negative refraction at optical frequencies in nonmagnetic two-component molecular
      media.
AB  - There is significant motivation to develop media with negative refractive indices
      at optical frequencies, but efforts in this direction are hampered by the
      weakness of the magnetic response at such frequencies. We show theoretically that
      a nonmagnetic medium with two atomic or molecular constituents can exhibit a
      negative refractive index. A negative index is possible even when the real parts
      of both the permittivity and permeability are positive. This surprising result
      provides a route to isotropic negative-index media at optical frequencies.

PMID- 16090989
TI  - Tunneling mechanism of light transmission through metallic films.
AB  - A mechanism of light transmission through metallic films is proposed, assisted by
      tunneling between resonating buried dielectric inclusions. This is illustrated by
      arrays of Si spheres embedded in Ag. Strong transmission peaks are observed near
      the Mie resonances of the spheres. The interaction among various planes of
      spheres and interference effects between these resonances and the surface
      plasmons of Ag lead to mixing and splitting of the resonances. Transmission is
      proved to be limited only by absorption. For small spheres, the effective
      dielectric constant of the resulting material can be tuned to values close to
      unity, and a method is proposed to turn the resulting materials invisible.

PMID- 16090990
TI  - Evidence for light-induced hole polarons in LiNbO3.
AB  - Transient light-induced absorption in LiNbO3 is observed in the blue-green
      spectral range after pulsed illumination with 532 nm. Its buildup and decay in Fe
      doped LiNbO3 is satisfactorily described by a sum of two stretched exponential
      functions. For undoped LiNbO3, however, only one stretched exponential decay is
      observed. These experimental results are explained by the formation of both small
      Nb(Li)4+ electron polarons and O- hole polarons. The mechanism is discussed on
      the basis of a proposed band scheme.

PMID- 16090991
TI  - Band-selective measurements of electron dynamics in VO2 using femtosecond near
      edge x-ray absorption.
AB  - We report on the first demonstration of femtosecond x-ray absorption
      spectroscopy, made uniquely possible by the use of broadly tunable bending-magnet
      radiation from "laser-sliced" electron bunches within a synchrotron storage ring.
      We measure the femtosecond electronic rearrangements that occur during the
      photoinduced insulator-metal phase transition in VO2. Symmetry- and element
      specific x-ray absorption from V2p and O1s core levels (near 500 eV) separately
      measures the filling dynamics of differently hybridized V3d-O2p electronic bands
      near the Fermi level.

PMID- 16090992
TI  - Velocity distributions of granular gases with drag and with long-range
      interactions.
AB  - We study velocity statistics of electrostatically driven granular gases. For two
      different experiments, (i) nonmagnetic particles in a viscous fluid and (ii)
      magnetic particles in air, the velocity distribution is non-Maxwellian, and its
      high-energy tail is exponential, P(upsilon) approximately exp(-/upsilon/). This
      behavior is consistent with the kinetic theory of driven dissipative particles.
      For particles immersed in a fluid, viscous damping is responsible for the
      exponential tail, while for magnetic particles, long-range interactions cause the
      exponential tail. We conclude that velocity statistics of dissipative gases are
      sensitive to the fluid environment and to the form of the particle interaction.

PMID- 16090993
TI  - Nearly smooth granular gases.
AB  - Hydrodynamic equations for nearly smooth granular gases are derived from the
      pertinent Boltzmann equation. The angular velocity distribution field needs to be
      included in the set of hydrodynamic fields. The angular velocity distribution is
      strongly non-Maxwellian for the homogeneous cooling state and any homogeneous
      steady state. In the case of steady wall-bounded shear flows the average spin
      (created at the boundaries) has a finite penetration length into the bulk.

PMID- 16090994
TI  - Statistics of particle velocities in dense granular flows.
AB  - We present measurements of the particle velocity distribution in the slow flow of
      granular material through vertical channels. The velocities of particles adjacent
      to the smooth, transparent front face of the channel were determined by video
      imaging and particle tracking. We find that the mean velocity changes sharply in
      shear layers near the side walls, but remains constant in a substantial core. The
      velocity distribution is non-Gaussian, is anisotropic, and follows a power law at
      large velocities. Remarkably, the distribution is identical in the shear layer
      and the core. We show evidence of spatially correlated motion, and propose a
      mechanism for the generation of fluctuational motion in the absence of shear.

PMID- 16090995
TI  - Thermodynamics of DNA loops with long-range correlated structural disorder.
AB  - We study the influence of a structural disorder on the thermodynamical properties
      of 2D-elastic chains submitted to mechanical/topological constraint as loops. The
      disorder is introduced via a spontaneous curvature whose distribution along the
      chain presents either no correlation or long-range correlations (LRC). The
      equilibrium properties of the one-loop system are derived numerically and
      analytically for weak disorder. LRC are shown to favor the formation of small
      loop, larger the LRC, smaller the loop size. We use the mean first passage time
      formalism to show that the typical short time loop dynamics is superdiffusive in
      the presence of LRC. Potential biological implications on nucleosome positioning
      and dynamics in eukaryotic chromatin are discussed.

PMID- 16090996
TI  - Effect of poisson ratio on cellular structure formation.
AB  - Mechanically active cells in soft media act as force dipoles. The resulting
      elastic interactions are long ranged and favor the formation of strings. We show
      analytically that due to screening, the effective interaction between strings
      decays exponentially, with a decay length determined only by geometry. Both for
      disordered and ordered arrangements of cells, we predict novel phase transitions
      from paraelastic to ferroelastic and antiferroelastic phases as a function of the
      Poisson ratio.

PMID- 16090997
TI  - Comment on "Attraction between nanoparticles induced by end-grafted homopolymers
      in good solvent".

PMID- 16090998
TI  - Role of mammalian lignans in the prevention and treatment of prostate cancer.
AB  - Prostate cancer is poised to become the most prevalent male cancer in the Western
      world. In Japan and China, incidence rates are almost 10-fold less those reported
      in the United States and the European Union. Epidemiological data suggest that
      environmental factors such as diet can significantly influence the incidence and
      mortality of prostate cancer. The differences in lifestyle between East and West
      are one of the major risk factors for developing prostate cancer. Traditional
      Japanese and Chinese diets are rich in foods containing phytoestrogenic
      compounds, whereas the Western diet is a poor source of these phytochemicals. The
      lignan phytoestrogens are the most widely occurring of these compounds. In vitro
      and in vivo reports in the literature indicate that lignans have the capacity to
      affect the pathogenesis of prostate cancer. However, their precise mechanism of
      action in prostate carcinogenesis remains unclear. This article outlines the
      possible role of lignans in prostate cancer by reviewing the current in vitro and
      in vivo evidence for their anticancer activities. The intriguing concept that
      lignans may play a role in the prevention and treatment of prostate cancer over
      the lifetime of an individual is discussed.

PMID- 16090999
TI  - Associations between black tea and coffee consumption and risk of lung cancer
      among current and former smokers.
AB  - Although cigarette smoking is a clear risk factor for lung cancer, the other
      determinants of lung cancer risk among smokers are less clear. Tea and coffee
      contain catechins and flavonoids, which have been shown to exhibit
      anticarcinogenic properties. Conversely, caffeine may elevate cancer risk through
      a variety of mechanisms. The current study investigated the effects of regular
      consumption of black tea and coffee on lung cancer risk among 993 current and
      former smokers with primary incident lung cancer and 986 age-, sex-, and smoking
      matched hospital controls with non-neoplastic conditions. Results indicated that
      lung cancer risk was not different for those with the highest black tea
      consumption (>or=2 cups/day) compared with nondrinkers of tea [adjusted odds
      ratio (aOR)=0.90; 95% confidence interval (CI)=0.66-1.24]. However, elevated lung
      cancer risk was observed for participants who consumed 2-3 cups of regular coffee
      daily (aOR=1.34; 95% CI=0.99-1.82) or >or=4 cups of regular coffee daily
      (aOR=1.51, 95% CI=1.11-2.05). In contrast, decaffeinated coffee drinking was
      associated with decreased lung cancer risk for both participants who consumed
      <or=1 cup/day (aOR=0.67; 95% CI=0.54-0.84) and those who consumed >or=2 cups/day
      (aOR=0.64; 95% CI=0.51-0.80). These results suggest that any chemoprotective
      effects of phytochemicals in coffee and tea may be overshadowed by the elevated
      risk associated with caffeine in these beverages.

PMID- 16091000
TI  - Urinary sex steroid excretion levels during a soy intervention among young girls:
      a pilot study.
AB  - Soy intake early in life may protect against breast cancer later in life,
      possibly by altering sex hormone metabolism. We evaluated the feasibility of
      assessing urinary sex steroid excretion among 20 young girls aged 8-14 yr in an 8
      wk trial. The girls consumed one daily soy serving, collected weekly overnight
      urine samples, and reported Tanner stages for breast and pubic hair development.
      Sex steroid excretion was measured in duplicate by gas chromatography-mass
      spectrometry and adjusted for urinary creatinine. The respective coefficients of
      variation for estrone, estradiol, estriol, testosterone, pregnanediol were 11.4%,
      10.4%, 8.4%, 12.8%, and 4.6%. The statistical analysis included t-tests,
      Spearman's correlations, and analysis of variance. Seventeen girls completed the
      study and showed good compliance with the intervention strategy. We observed
      nonsignificant increases in total androgens (0.11 microg/mg creatinine) and total
      estrogens (0.001 microg/mg creatinine) and a nonsignificant decrease in
      pregnanediol (-0.03 microg/mg creatinine) during the study period. Higher Tanner
      stages for pubic hair development were associated with ninefold higher estrogen,
      fourfold higher androgen, and twofold higher pregnanediol excretions (P=0.01,
      P<0.001, and P=0.047, respectively). Similar differences were observed after
      stratification by breast development and menarcheal status. The association of
      sex steroid levels with pubertal development supports the validity of the sex
      steroid measurements.

PMID- 16091001
TI  - Early percutaneous endoscopic gastrostomy insertion maintains nutritional state
      in patients with aerodigestive tract cancer.
AB  - Patients with upper aerodigestive tract (UAT) cancers often suffer from
      malnutrition and compromised functional ability. We compared clinical outcome
      with percutaneous endoscopic gastrostomy (PEG) tube feeding begun at two
      different time points. The records of 151 patients with UAT carcinomas were
      reviewed retrospectively. We included patients undergoing radical
      radiochemotherapy and PEG tube feeding. Subjects were evaluated before PEG
      insertion and at the end of the treatment. Patients (n=15, 100%) were divided
      into two groups according to the presence (group A) or absence (group B) of
      mucositis. Group A (51.7% of patients) received early PEG: before or within 2 wk
      of radiotherapy. Group B (48.3%) received delayed PEG: between 2 wk and 3 mo
      after the start of radiotherapy. Mean weight loss was 1.03 kg in group A vs. 4.0
      kg in group B, P=0.004. Treatment interruptions were significantly (P=0.01) more
      common in group B. Early PEG placement at the beginning of radiochemotherapy in
      patients with UAT tumors maintains the patient's nutritional state and reduces
      treatment interruptions.

PMID- 16091002
TI  - Human fecal water modifies adhesion of intestinal bacteria to Caco-2 cells.
AB  - The aqueous phase of feces (fecal water) has been suggested to mediate the
      effects of diet on colon carcinogenesis. We determined whether human fecal water
      samples, of varying genotoxic potential, had the capacity to alter adhesion of
      intestinal bacteria to intestinal (Caco-2) cells. Genotoxicity of fecal water
      samples was measured using the single-cell gel electrophoresis assay ("comet"
      assay), and bacterial adhesion was measured using a well-established model
      system. Fecal water genotoxicity was found to correlate positively with
      inhibition of adhesion of Escherichia coli strains, Salmonella species, and
      Enterococcus faecium to Caco-2 cells. The presence of fecal water samples did not
      interfere with adhesion of Bacteroides and Lactobacillus species. Inhibition of
      adhesion by fecal water was not due to cytotoxicity to Caco-2 cells as
      cytotoxicities of most fecal water samples were similar, nor was the inhibitory
      effect due to bacteriotoxicity as toxicity of fecal waters in the 10 strains of
      bacteria studied was not detected. Results indicate that components in fecal
      water may alter adhesion of intestinal bacteria to intestinal cell surfaces and
      that this effect may be correlated to the genotoxic potential of fecal water.
      This may have consequences for dietary effects on colon carcinogenesis.

PMID- 16091003
TI  - Novel interactions of vitamin E and estrogen in breast cancer.
AB  - The prevention of breast cancer through dietary modification is an active area of
      clinical and epidemiological research. It has been proposed that dietary
      supplementation of vitamin E may reduce a woman's risk of developing breast
      cancer. However, the exact mechanism remains unknown. alpha-Tocopherol is the
      most biologically active form of vitamin E. We investigated the effect of vitamin
      E (alpha-tocopherol) on breast cancer cell growth. A dose-dependent inhibition of
      cell proliferation was found in estrogen receptor (ER)-positive cells showing a
      potent suppression of growth at 100 microM vitamin E in MCF-7 (53%) and T47D
      (75%) cells. Vitamin E reduced significantly the response of both cell lines to
      estrogen (10 nM), and cell proliferation was decreased in MCF-7 and T47D cells by
      69% and 84%, respectively. No growth inhibition was observed when cells were
      grown in the absence of estrogen. Vitamin E altered and decreased the growth
      inhibition induced by tamoxifen (10 microM) in MCF-7 (33%) and T47D (54%) cells.
      In addition, the immunostaining of ER of MCF-7 cells was reduced by 30% in the
      presence of vitamin E, suggesting an effect of vitamin E on the expression of ER.
      This provides evidence that vitamin E may inhibit ER-positive cell growth by
      altering the cellular response to estrogen.

PMID- 16091004
TI  - Induction of NAD(P)H quinone oxidoreductase by vegetables widely consumed in
      Catalonia, Spain.
AB  - Monofunctional inducers (MIs) enhance phase 2 enzymes such as nicotinamide
      adenine-dinucleotide-phosphate [NAD(P)H] quinone oxidoreductase (NQO1) without
      modifying oxidation enzymes. The induction of these protective enzymes appears to
      be mediated by genetic regulatory elements in their promoter regions known as the
      antioxidant response element (ARE). The aim of this study was to identify,
      through an in vitro study, which of the 30 fruits and vegetables commonly
      consumed in Catalonia, Spain, contain MIs of NQO1. We assayed the capacity of
      extracts of these fruits and vegetables to induce NQO1 [by more than 1.5-fold:
      ratio of induction (cells treated/control) >1.5, 8-mg/ml dose] in two murine
      hepatoma cell lines: Hepa 1c1c7 and BPrC1, a modified cell line that possesses a
      nonfunctional aryl hydrocarbon receptor nuclear translocator system and is thus
      nonresponsive to bifunctional inducers. We also used a third cell line, papiloma
      (PE) murine keratinocytes, a stably transfected cell line with an ARE-luc+
      plasmid (AREPE cell line) for verifying induction through the ARE with a simple
      luminescence screening assay. Broccoli (Hepa 1c1c7, ratio=5.5; BPrC1, ratio=2.3),
      calcot (Allium cepa L.) (Hepa 1c1c7, ratio=4.7; BPrC1, ratio=.5), green onion
      (Hepa 1c1c7, ratio=4.6; BPrC1, ratio=2), green cabbage (Hepa 1c1c7, ratio=3.6;
      BPrC1, ratio=2.7), purple cabbage (Hepa 1c1c7, ratio=3.4; BPrC1, ratio=2), and
      black cabbage (Hepa 1c1c7, ratio=3; BPrC1, ratio=3) were active NQO1 inducers in
      both murine hepatoma cell lines. Extracts from broccoli (ratio=3.5), calcot
      (ratio=4.8), cauliflower (ratio=4.2), cabbage (ratio=2.2), green onion
      (ratio=3.2), green cabbage (ratio=3.6), black cabbage (ratio=4.5), and purple
      cabbage (ratio=3.7) were confirmed to contain MIs in the AREPE cell line. These
      results are very similar to those described for vegetables consumed in the United
      States, with the exception of calcot, which is common in Catalonia but is not
      grown or consumed widely in the United States.

PMID- 16091005
TI  - Effect of resveratrol on angiogenesis and platelet/fibrin-accelerated tumor
      growth in the chick chorioallantoic membrane model.
AB  - We carried out this investigation to examine the effects on angiogenesis-mediated
      processes and to define anti-angiogenesis mechanisms for flavonoids. We examined
      the effects and mechanisms of the flavonoid resveratrol on angiogenesis and tumor
      growth using the chick chorioallantoic membrane (CAM) model of angiogenesis, the
      CAM tumor growth model, and the effect on p53 in fibroblast growth factor-2
      (FGF2) stimulated human endothelial cells using immunoassay. Resveratrol
      demonstrated potent inhibition (effective dose50=0.7+/-0.1 microM) of FGF2
      induced angiogenesis and tumor growth. Furthermore, resveratrol significantly
      (P<0.01) inhibited platelet/fibrin clot-promoted human colon and fibrosarcoma
      tumor growth in the CAM tumor model. Resveratrol in a concentration-dependent (1
      3 microM) manner significantly promoted apoptosis in FGF2-stimulated endothelial
      cells by increasing p53 protein production. These data indicated potent anti
      angiogenesis efficacy, inhibition of tumor growth, and clot-mediated enhanced
      tumor growth. These data suggest potential anticancer benefits as a
      chemopreventive and chemotherapeutic for the flavonoid resveratrol.

PMID- 16091006
TI  - Green tea polyphenols modulate secretion of urokinase plasminogen activator (uPA)
      and inhibit invasive behavior of breast cancer cells.
AB  - Many epidemiological studies have suggested that consumption of green tea may
      decrease the risk of cancer. The chemopreventive effect of green tea polyphenols
      (GTP) has been demonstrated through the inhibition of cell proliferation and
      angiogenesis in cell culture and animal models of breast cancer. Metastasis of
      breast cancer is the major reason for the high mortality of breast cancer
      patients and is directly linked to the invasive behavior of breast cancer cells.
      Cancer metastasis consists of several interdependent processes including cancer
      cell adhesion, cancer cell migration, and invasion of cancer cells. In this
      study, we evaluated the effect of GTP on human breast cancer cells, and we show
      that in addition to inhibiting cell growth, GTP also suppressed the invasive
      behavior of MDA-MB-231 cells. These anti-invasive effects of GTP were the result
      of the inhibition of constitutively active transcription factors AP-1 and NF
      kappaB, which further suppressed secretion of urokinase plasminogen activator
      (uPA) from breast cancer cells. Based on these results, it can be hypothesized
      that GTP treatment resulted in the inhibition of formation of signaling complexes
      responsible for cell adhesion and migration (uPA, uPA receptor, vitronectin,
      integrin receptor) and cell invasion (uPA, uPA receptor). Our results indicate
      that GTP may contribute to the anticancer effects of green tea by inhibiting the
      invasive behavior of cancer cells.

PMID- 16091007
TI  - Antioxidant and cytotoxic properties of lyophilized beer extracts on HL-60 cell
      line.
AB  - An impressive number of studies have suggested that red wine can be considered
      the protective beverage of choice against chronic and degenerative pathologies.
      Only few and controversial data are available on a potential, similar role for
      beer, which represents a more cost-effective, safe, and widely available
      beverage. Starting from the evidence that many antioxidant compounds present in
      red wine are also present at similar or even higher concentrations in beers, we
      first screened 48 commercially available beers and selected one (Mrt-HP) with
      very high polyphenol concentration and antioxidant activity estimated by ferric
      reducing antioxidant power. We demonstrated that a lyophilized preparation of Mrt
      HP beer was cytotoxic with respect to a beer with low polyphenolic content (Trt
      LP) when assayed on HL-60 human leukemia cell line. We measured a 60% decrease in
      cell viability at a polyphenol concentration of 250 microM quercetin equivalents.
      We also demonstrated that Mrt-HP cytotoxicity was not an artifact due to cell
      growth conditions because addition of Mrt-HP extracts to cell medium generated
      peroxide levels indistinguishable from controls. By means of cytofluorimetric
      analysis of pre-G1 population and caspase 3 activation, we demonstrated that Mrt
      HP extracts activated apoptosis in HL-60 cell line. Finally, we found that the
      concentration of quercetin, resveratrol, and gallic acid in Mrt-HP was 10, 4.6,
      and 4.6-fold higher, respectively, than in Trt-LP, suggesting that the presence
      of these molecules might be responsible for the observed cytotoxicity. These
      data, together with the low in vivo beer toxicity reported in the literature,
      suggest a possible chemopreventive role for this beverage that requires further
      studies in animal models.

PMID- 16091008
TI  - Effects of genistein on the polyamine metabolism and cell growth in DLD-1 human
      colon cancer cells.
AB  - Polyamines and their rate-limiting enzyme, ornithine decarboxylase (ODC), are
      actively involved in cell growth and differentiation. The phytoestrogen genistein
      has been demonstrated to possess antitumor properties by influencing
      proliferation, differentiation, and apoptosis. The aim of this study was to
      investigate the effects of genistein at concentrations ranging from 0.01 to 100
      microM on the polyamine biosynthesis, cell proliferation, and apoptosis in the
      estrogen receptor-positive DLD-1 human colon cancer cell line. Polyamine levels
      and ODC activity were evaluated by high performance liquid chromatography and
      radiometric technique, respectively. The proliferative response was estimated by
      [3H]-thymidine incorporation and the colorimetric 3-(4,5 di-methylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide test. Apoptosis was investigated by DNA
      fragmentation. Bax and Bcl-2 gene expressions were evaluated by multiplex
      polymerase chain reaction. At concentration >or=1 microM, genistein decreased
      significantly the ODC activity and the polyamine levels. At the same
      concentration, genistein also increased significantly Bax mRNA expression, but
      not Bcl-2 mRNA expression. Higher concentrations (>or=10 microM) were needed to
      obtain a significant inhibition of cell proliferation and DNA fragmentation. The
      results of this study suggest that genistein can affect growth of DLD-1 cells by
      both decreasing polyamine biosynthesis and inducing apoptosis. However, further
      studies are required to assess the true ability of a soy rich diet in modifying
      colon cancer risk.

PMID- 16091009
TI  - In vitro effects on polydextrose by colonic bacteria and caco-2 cell
      cyclooxygenase gene expression.
AB  - A 4-stage colon simulator and a cell culture-based human intestinal epithelial
      function model were combined to study the effects of a soluble fiber,
      polydextrose (PDX), on intestinal microbes and mucosal functions relevant to the
      risk of colon cancer. We observed sustained degradation of PDX throughout the
      different stages of the model. The fermentation was characterized by gradual
      degradation of PDX, production of short-chain fatty acids, and no increasing in
      putrefactive markers. We observed less marked effects in the microbial densities.
      When we applied colon fermentation metabolites obtained from the simulators with
      PDX to Caco-2 colon cancer cell line, a significant dose-dependent decreasing
      effect on cyclooxygenase-2 (COX-2) and an increasing effect on COX-3 expression
      levels were observed. PDX concentration appeared not to have effect on the
      expression levels of COX-1. Overexpression of COX-2 and decreased expression of
      COX-1 have been suggested to be characteristics of colon cancer. The exact
      physiological role of COX-3, an intron-retaining splice variant of COX-1, is not
      known, but it is suspected to play a role in transcriptional regulation of COX-1
      and COX-2. In vitro modulation of COX expression by colon microbial fermentation
      products of polydextrose offers an interesting starting point for further studies
      on possible risk-decreasing effect of PDX on the development of colon cancer.

PMID- 16091010
TI  - Upregulation of connexin 43 by retinoids but not by non-provitamin A carotenoids
      requires RARs.
AB  - Expression of connexin 43 (Cx43) is correlated with reduced indexes of neoplasia
      and is upregulated by cancer-preventive retinoids and carotenoids in
      nontransformed human and murine fibroblasts and keratinocytes. The molecular
      mechanism of upregulation, however, is poorly understood. Three retinoic acid
      receptor (RAR) antagonists (Ro 41-5253, BMS453, and BMS493) were capable of
      suppressing retinoid-induced Cx43 protein expression in 10T1/2 cells. However, Ro
      41-5253 did not suppress protein expression by the non-provitamin A carotenoids
      astaxanthin or lycopene. In contrast, Cx43 induction by astaxanthin but not by a
      RAR-specific retinoid was inhibited by GW9662, an antagonist of peroxisome
      proliferator activated receptor-gamma activation. Simultaneous treatment with the
      maximally effective concentration of a retinoid and with beta-carotene or the non
      provitamin A carotenoid astaxanthin resulted in supraadditive upregulation of
      Cx43 expression, again indicating separate mechanisms of gene regulation by these
      two cancer preventive agents.

PMID- 16091016
TI  - The shed ectodomain of type XIII collagen associates with the fibrillar
      fibronectin matrix and may interfere with its assembly in vitro.
AB  - Type XIII collagen is a transmembrane collagen, which is known to exist also as a
      soluble variant due to ectodomain shedding. Earlier studies with the recombinant
      ectodomain have shown it to interact in vitro with a number of extracellular
      matrix proteins, e.g. Fn (fibronectin). In view of its strong binding to Fn, we
      examined in the present study whether the released soluble ectodomain can bind to
      the fibrillar Fn matrix under cell-culture conditions and, if so, influence its
      assembly. In this study, we demonstrate that the type XIII collagen ectodomain of
      mammalian cells can associate with Fn fibres and may eventually hamper
      incorporation of the fibrillar Fn meshwork. The association between type XIII
      collagen and Fn was implicated to be mediated by the C-terminal end of type XIII
      collagen and the N-terminal end of Fn. The results presented here imply that the
      shedding of the type XIII collagen ectodomain results in a biologically active
      molecule capable of remodelling the structure of the pericellular matrix.

PMID- 16091017
TI  - Specific role for p85/p110beta in GTP-binding-protein-mediated activation of Akt.
AB  - We prepared CHO (Chinese hamster ovary) cells expressing both IR (insulin
      receptor) and A1R (A1 adenosine receptor). Treatment of the cells with insulin or
      PIA [N6-(2-phenylisopropyl)adenosine], a specific A(1)R agonist increased Akt
      activity in the cells in a PI3K- (phosphoinositide 3-kinase) dependent manner.
      Transfection of p110beta into the cells augmented the action of PIA with little
      effect on insulin. Introduction of a pH1 vector producing shRNA (short hairpin
      RNA) that targets p110beta abolished PIA-induced Akt activation. By contrast, an
      shRNA probe targeting p110alpha did not impair the effects of PIA. The effect of
      PIA in p110alpha-deficient cells was attenuated effectively by both Deltap85 and
      betaARK-CT (beta-adrenergic receptor kinase-C-terminal peptide). A Deltap85
      derived protein possessing point mutations in its two SH2 domains did not impair
      PIA action. These results suggest that tyrosine-phosphorylated proteins and
      Gbetagamma (betagamma subunits of GTP-binding protein) are necessary for the
      specific function of p110beta in intact cells. The p110beta-middle (middle part
      of p110beta) may play an important role in signal reception from GPCRs (GTP
      binding-protein-coupled receptor), because transfection of the middle part
      impaired PIA sensitivity.

PMID- 16091018
TI  - 13C- and 2H-labelled glucose compared for minimal model estimates of glucose
      metabolism in man.
AB  - In the present study, we have investigated the use of 1-[(13)C]glucose and
      GC/combustion/isotope-ratio MS as an alternative to 6,6-[(2)H(2)]glucose and
      GC/MS in the determination of parameters of glucose metabolism using the IVGTT
      (intravenous glucose tolerance test) interpreted by labelled (hot) minimal
      models. The study has been done in four populations, normoglycaemics (subdivided
      into lean and obese individuals), subjects with impaired glucose tolerance and
      those with diabetes mellitus. Although the use of carbon label may in some
      circumstances be compromised by substrate recycling, our hypothesis was that this
      would not be an issue under the condition of suppression of hepatic glucose
      production during the short timescale of an IVGTT. In all four groups, we found
      that the methodology employing the carbon label gave equivalent results to those
      obtained using the conventional deuterated material, but the sensitivity of the
      measurement technique in the new approach was sufficient to allow an approx. 15
      fold reduction in the quantity of isotope administered. In addition to the clear
      cost advantages, this represents a significant scientific advance in that true
      tracer status is more nearly attained in these measurements with near
      physiological tracee loads.

PMID- 16091019
TI  - Establishing the cost-effectiveness of new pharmaceuticals under conditions of
      uncertainty--when is there sufficient evidence?
AB  - Decisions about which health-care interventions represent adequate value to
      collectively funded health-care systems are as widespread as they are
      unavoidable. In the case of new pharmaceuticals, many countries now require
      formal cost-effectiveness analysis to inform this decision-making process. This
      requires evidence on parameters associated with health-related utilities,
      treatment effects, resource use, and costs, for which data from available
      regulatory trials are invariably absent or highly uncertain. This uncertainty
      results from a number of factors including the predominance of intermediate end
      points in the clinical evidence-base and the limited period of follow-up of
      patients in clinical studies. Despite these imperfections in the evidence base,
      decisions about whether new pharmaceuticals are sufficiently cost-effective for
      reimbursement cannot be side-stepped. Data limitations do, however, require the
      use of rigorous analytical methods to support decision making. Probabilistic
      decision models and value of information analysis offer a means of structuring
      decision problems, synthesizing all available data, characterizing the
      uncertainty in the decision, quantifying the cost of uncertainty, and
      establishing the expected value of perfect information. This analytical framework
      is important because it addresses two fundamental questions about new
      pharmaceuticals. First, is the product expected to be cost-effective on the basis
      of existing evidence? Second, is additional research concerning the product
      itself cost-effective? In addressing these questions, the analytical framework
      can establish when sufficient evidence exists to sustain a claim for a new
      pharmaceutical to be cost-effective.

PMID- 16091020
TI  - An aging population--burden or blessing?

PMID- 16091021
TI  - Evidence-based practice to evidence-based policy: do we really impact on patient
      care?

PMID- 16091022
TI  - Understanding patient preferences for HIV medications using adaptive conjoint
      analysis: feasibility assessment.
AB  - OBJECTIVE: Choosing among HIV medications involve making trade-offs among various
      efficacy, convenience, resistance, and side-effect attributes. This study tested
      the feasibility of using adaptive conjoint analysis (ACA) to assess preferences
      (utilities) for HIV medication attributes. METHODS: HIV individuals were
      recruited through newspaper advertisements. Participants completed a computerized
      ACA survey that assessed 12 attributes, including side effects, regimen
      convenience, resistance, and efficacy. Literature on third-agent HIV drugs was
      used to identify percentage risk and severity level descriptions for each
      attribute. Based on the ACA-derived utilities, we assessed the relative
      importance of the attributes by averaging individually calculated importance and
      estimated the percentages that would prefer selected HIV medications over others.
      To check validity of the ACA utilities, the survey also had respondents choose
      among medications with different attribute profiles. RESULTS: The 35 respondents
      were primarily African Americans (94%) and unemployed (54%). Of these, 28 (80%)
      provided consistent responses and were analyzed. Of the 12 medication attributes
      evaluated, the risk of developing resistance, regimen convenience, and the risk
      of sleep disturbance had the greatest impact on preferences; each accounting for
      more than 8.5% of the variation in preferences. These were followed by risk of
      drug failure (8.2%), cholesterol elevation (7.1%), diarrhea (7.1%) and nausea
      (6.9%). The ACA utilities accurately predicted patients' actual medication
      choices 75% of the time. CONCLUSIONS: Adaptive conjoint analysis was successful
      in predicting HIV treatment preferences under different medication scenarios.
      Resistance, regimen convenience, and sleep disturbance would likely make the most
      difference in the perceived value of a third-agent HIV medication.

PMID- 16091023
TI  - Cost-effectiveness analysis of rituximab combined with chop for treatment of
      diffuse large B-cell lymphoma.
AB  - PURPOSE: To estimate the cost-effectiveness from a French payer perspective of
      CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) alone compared
      with CHOP plus rituximab (R-CHOP) for treatment of patients with diffuse large B
      cell lymphoma. METHODS: Mean patient survival, days of hospitalization, and
      chemotherapy costs during treatment were estimated from a Phase III trial in
      France, Belgium, and Switzerland. Survival during the trial was estimated using
      the Kaplan-Meier method; survival beyond the trial period was projected based on
      mortality rates from the Scottish and Newcastle Lymphoma Group database. French
      diagnosis-related group (DRG) payment schedules were applied to trial data to
      estimate cost of adverse events and drug administration. We estimated survival
      and cost-effectiveness [the incremental cost per quality-adjusted life-year
      (QALY) gained] from 4 years (median clinical trial follow-up period) to 15 years,
      discounted at a fixed annual rate of 3%. We used published patient preferences.
      We converted currency to euros, based on 2003 exchange rates. RESULTS: R-CHOP
      resulted in a 20.6% relative increase in complete response rate (absolute
      increase from 63% to 76%), and a 31% decrease in risk of death at 4 years (95% CI
      8-49%). Over a 15-year time horizon, mean overall survival (OS) duration was
      estimated to be 6.90 years for R-CHOP and 5.74 years for CHOP, a mean increase in
      OS of 1.16 years (or 1.07 QALYs). Total direct medical costs were 13,170 euro
      higher with R-CHOP, with an incremental cost-effectiveness ratio of 12,259 euro
      per QALY gained. CONCLUSION: R-CHOP significantly increases mean OS up to 4 years
      compared with CHOP, and its cost-effectiveness ratio compares favorably with
      other oncology treatments in widespread use.

PMID- 16091024
TI  - Relationship between initial quetiapine dose and effectiveness as reflected in
      subsequent mental health service use among patients with schizophrenia or bipolar
      disorder.
AB  - OBJECTIVE: To investigate the association between initial quetiapine dose and
      effectiveness as gauged by subsequent use of mental health services. METHODS:
      Using a health plan database, we identified patients with bipolar disorder or
      schizophrenia treated with quetiapine monotherapy for at least four consecutive
      months. The stability of each patient before and after quetiapine treatment was
      measured by use of mental health services other than antipsychotic drug, measured
      primarily by charges reported on claims. Regression models controlling for
      patient differences measured associations between initial quetiapine dose and
      subsequent mental health service use. RESULTS: Commercially insured patients with
      schizophrenia (n = 581) or bipolar disorder (n = 2421) received quetiapine
      monotherapy at mean (SD) initial daily doses of 237 (198) mg and 147 (171) mg,
      respectively. Both groups showed negative associations between initial daily dose
      and subsequent mental health charges. Among patients with schizophrenia, mental
      health charges decreased by US 1.28 dollars for each additional milligram of
      quetiapine (P = 0.1097). Among patients with bipolar disorder, there was a
      significant decrease of US 1.31 dollars per additional milligram of quetiapine (P
      = 0.0484). For schizophrenia, hospitalizations were reduced by 0.4% for each
      additional milligram of quetiapine (P = 0.0189). For bipolar disorder, the
      association between quetiapine dose and outpatient charges was negative and
      trended toward significance (P = 0.074), showing a US 0.54 dollars reduction in
      these charges for each additional milligram of quetiapine; the association with
      hospitalization was not significant. CONCLUSIONS: In patients with schizophrenia
      or bipolar disorder, higher initial doses of quetiapine may be more effective in
      stabilizing patients as reflected in lower subsequent mental health service use.

PMID- 16091025
TI  - Eliciting women's preferences for a training program in breast self-examination:
      a conjoint ranking experiment.
AB  - OBJECTIVES: Although the clinical grounds for recommending breast self
      examination (BSE) have been extensively debated in the literature, there has been
      no investigation into women's preferences for BSE training. The aim of this study
      was to test the conjoint ranking method using data on women's preferences for
      different BSE training programs. Different econometric specifications were tested
      and sample subgroup differences were investigated. METHODS: Postal data were
      collected from 1258 women with and without previous participation in a BSE
      training program. The women ranked eight hypothetical training programs that were
      defined in terms of three attributes. Inclusion of a payment attribute enabled
      the calculation of marginal willingness-to-pay (WTP) estimates. RESULTS: The
      marginal WTP for individual training in comparison to group training with 18 to
      20 participants was estimated to be 225 Danish Kroner (DKK) to 462 DKK. The
      marginal WTP for training in groups of eight to 10 participants was 180 DKK to
      270 DKK. The respondents also preferred to receive instruction using their own
      breasts, although this was valued lower than a small group size. The results were
      similar regardless of whether or not the women had previously participated in BSE
      training. Around 20% of respondents violated a basic assumption of economic
      theory, in which the cheaper of two otherwise identical goods should be
      preferred. CONCLUSIONS: Conjoint ranking can provide comprehensive information
      about benefit assessment. The approach is cognitively demanding, however, and may
      cause some respondents to violate the axiom of nonsatiation.

PMID- 16091026
TI  - Cost savings from intravenous immunoglobulin manufactured from
      chromotography/caprylate (IGIV-C) in persons with primary humoral
      immunodeficiency disorder.
AB  - OBJECTIVE: Human intravenous immunoglobulin manufactured with chromatography and
      caprylate methods (IGIV-C, 10%) was associated with a reduction in validated
      infections (pneumonia and sinusitis) compared with treatment with a licensed
      immunoglobulin product manufactured using standard solvent-detergent methods
      (IGIV-SD, 10%) in participants with primary humoral immunodeficiency disorder
      (PIDD). Our objective was to determine the cost-consequences of using IGIV-C
      instead of IGIV-SD. METHODS: Economic analysis of a double-blind, randomized,
      clinical trial was used. Participants were randomly assigned to IGIV-C (N = 87)
      or IGIV-SD (N = 85) and monitored for the development of validated infections
      over the course of 9 months. Consumed resources were enumerated including cost of
      physician and emergency room visits, medications (prescription and over-the
      counter), work productivity losses, and hospitalizations. Resource data was
      obtained from case report forms, patient diaries and the trial medication
      database. Because the amount of IGIV-SD used exceeded that of IGIV-C
      (nonstatistically significant difference) and the products are equivalently
      priced, we conservatively excluded investigational product acquisition cost to
      avoid artificially biasing incremental cost differences. We used a societal
      perspective with indirect costs, measured in 2003 US dollars. Pricing of both
      IGIV products is anticipated to be equivalent. RESULTS: In a multivariate
      analysis, annual mean per participant costs were significantly lower between
      those receiving IGIV-C compared with IGIV-SD for prescription medications [-US
      302 dollars, 95% confidence interval (CI) -US 598 dollars to -US 6 dollars],
      hospitalization (-US 1454 dollars, 95% CI -US 1828 dollars to -US 1080 dollars)
      and total costs (-US 1304 dollars, 95% CI -US 1867 dollars to -US 742 dollars).
      Costs associated with lost work productivity and physician visits were similar in
      both groups (P > 0.10). In sensitivity analyses, varying costs of concomitant
      medications, hospitalization and outpatient care, did not significantly change
      our results. CONCLUSION: IGIV-C is cost-saving compared with IGIV-SD among
      persons with PIDD.

PMID- 16091027
TI  - Persistence and adherence of medications for chronic overactive bladder/urinary
      incontinence in the california medicaid program.
AB  - OBJECTIVES: To investigate persistence and adherence of medication treatment in
      chronic overactive bladder/urinary incontinence (OAB/UI) patients, and to
      evaluate OAB/UI-related comorbidity events associated with persistence. METHODS:
      Pharmaceutical outcomes research with a health-care provider perspective was
      conducted on a California Medicaid (Medi-Cal) chronic OAB/UI population. The
      primary end point was medication possession ratio (MPR), which was used to
      measure refill adherence. Secondary end points measuring persistence patterns
      included discontinuation of OAB drug therapy (medication-uncovered interval > 30
      days) and time to discontinuation (period from the index date until the first
      discontinuation date). Significant factors on nonpersistence were found by using
      a Cox Proportional Hazards model. Factors contributing to nonadherence (MPR <
      0.8) and the relationship between OAB/UI comorbidity events and persistence were
      examined by logistic regressions. RESULTS: Of 2496 eligible patients, 36.9% had
      only one OAB/UI prescription. The mean MPR was 0.34 (SD 0.21) and the median was
      0.3, indicating that on average only about one-third of period of time since
      medication initiation was covered by the therapy. Only 122 patients exhibited >
      80% adherence during the 6-month follow-up-period. Significant predictors of
      higher persistence included: white ethnicity, previous hospitalization length,
      starting with tolterodine or oxybutynin extended-release, and previous use of
      topical drugs or antipsychotics. Nevertheless, previous depression or urinary
      tract infection (UTI) diagnosis, polypharmacy, significantly increased the odds
      of early discontinuation. Treatment discontinuation increased the risk of UTI
      diagnosis by 37% in the post-treatment period (P = 0.03; OR 1.37; 95% CI 1.03
      1.84), but had no significant effect on other OAB/UI-related comorbidities.
      CONCLUSIONS: For chronic OAB/UI patients identified in this study, both
      persistence and adherence with medication treatment were suboptimal. These
      results suggest that persistence and treatment discontinuation remains
      problematic for the OAB/UI population.

PMID- 16091028
TI  - Cost and utilization impacts of oral antihistamines in the California Medi-Cal
      program.
AB  - OBJECTIVES: Newer oral allergic rhinitis (AR) medications, the second-generation
      antihistamines (SGAs) have gained widespread acceptance because of their efficacy
      and reduced side effects relative to first-generation antihistamines (FGAs).
      There are no empirical studies comparing the costs of treatment of SGAs relative
      to FGAs. METHODS: We analyzed data from a 20% beneficiary sample (approximately
      120,000 continuously enrolled beneficiaries per year) for the Medi-Cal Fee-for
      Service program during 1999 to 2000. AR medications available under Medi-Cal
      included three SGA medications (loratadine, fexofenadine, and cetirizine) and
      over 200 FGA products containing either diphenhydramine or chlorpheniramine or
      both. Because multiple medications were evaluated, a sample selection model was
      estimated using a two-stage multinomial logistic--variance components regression
      framework. RESULTS: SGA medications have significantly lower total direct health
      care treatment costs per patient than FGA medications with costs ranging from US
      347 dollars to US 448 dollars less (P < 0.001), despite higher AR medication
      costs. Total drug expenditures were also not significantly different for patients
      using SGA or FGA medications despite SGA prescriptions averaging US 47 dollars
      higher than FGAs. Emergency department visits, inpatient admissions and physician
      office visits were also significantly lower for patients using SGA medications.
      CONCLUSIONS: Significant cost and utilization reductions were associated with all
      of the SGA medications relative to FGA drugs, despite their higher acquisition
      costs. If facing higher copayments for prescription AR drugs, many patients,
      particularly lower income patients, may choose cheaper over-the-counter (OTC)
      FGAs rather than SGAs. Our analysis finds this might lead to increased overall
      health-care treatment costs, unless Medicaid and health insurance plans subsidize
      OTC AR medications.

PMID- 16091029
TI  - Obituary: J.-M. Ghuysen.

PMID- 16091030
TI  - Multiple drug resistance genes in malaria -- from epistasis to epidemiology.
AB  - A decline in our ability to successfully treat patients with malaria infections
      of the parasitic protozoan Plasmodium falciparum with cheap quinoline drugs has
      led to a huge escalation in morbidity and mortality in recent years. Many
      approaches have been taken, including classical genetics, reverse genetics and
      molecular epidemiology, to identify the molecular determinants underlying this
      resistance. The contribution of the P. falciparum multidrug resistance gene,
      pfmdr1, to antimalarial resistance has been a source of controversy for over a
      decade since it was first identified. In the current issue of Molecular
      Microbiology, Sidhu and colleagues use powerful reverse genetics to demonstrate
      the importance of commonly occurring alleles of pfmdr1 in conferring resistance
      to the second-line drugs quinine and sensitivity to the new alternatives
      mefloquine and artemisinin. They also elegantly highlight the importance of
      genetic background and epistasis between pfmdr1 and other potential modulators of
      drug resistance. Such molecular knowledge will facilitate surveillance/monitoring
      and aid the development of strategies for the reversal of resistance.

PMID- 16091031
TI  - Weapons of mass retraction.
AB  - Twitching motility is a unique form of bacterial propulsion on solid surfaces
      associated with cycles of extension, tethering and retraction of type IV pili
      (T4P). Although investigations over the last two decades in a number of species
      have identified the majority of the genes involved in this process, we are still
      learning how these pili are assembled and the mechanics by which bacteria use T4P
      to drag themselves from one place to another. Among the puzzles that remain to be
      solved is the mechanism by which hydrolysis of ATP is coupled to pilus assembly
      and disassembly, and how the cell envelope structure is modified to accommodate
      the passage of the pilus through the periplasm. Unravelling of these and other
      enigmas in the T4P system will not only teach us more about these important
      colonization and virulence factors, but also help us to understand related
      processes such as type II secretion, which relies on a set of proteins homologous
      to those in the T4P system, and bacterial conjugation, involving retractable pili
      belonging to the F-like subgroup of the type IV secretion family. This review
      focuses on recent discoveries relating to the assembly and function of T4P in
      generation of twitching motility.

PMID- 16091032
TI  - Facilitated diffusion in chromatin lattices: mechanistic diversity and regulatory
      potential.
AB  - The interaction between a protein and a specific DNA site is the molecular basis
      for vital processes in all organisms. Location of the DNA target site by the
      protein commonly involves facilitated diffusion. Mechanisms of facilitated
      diffusion vary among proteins; they include one- and two-dimensional sliding
      along DNA, direct transfer between uncorrelated sites, as well as combinations of
      these mechanisms. Facilitated diffusion has almost exclusively been studied in
      vitro. This review discusses facilitated diffusion in the context of the living
      cell and proposes a theoretical model for facilitated diffusion in chromatin
      lattices. Chromatin structure differentially affects proteins in different modes
      of diffusion. The interplay of facilitated diffusion and chromatin structure can
      determine the rate of protein association with the target site, the frequency of
      association-dissociation events at the target site, and, under particular
      conditions, the occupancy of the target site. Facilitated diffusion is required
      in vivo for efficient DNA repair and bacteriophage restriction and has potential
      roles in fine-tuning gene regulatory networks and kinetically compartmentalizing
      the eukaryotic nucleus.

PMID- 16091033
TI  - The lipid A palmitoyltransferase PagP: molecular mechanisms and role in bacterial
      pathogenesis.
AB  - Palmitoylated lipid A can both protect pathogenic bacteria from host immune
      defences and attenuate the activation of those same defences through the TLR4
      signal transduction pathway. A palmitate chain from a phospholipid is
      incorporated into lipid A by an outer membrane enzyme PagP, which is an 8
      stranded antiparallel beta-barrel preceded by an amino-terminal amphipathic alpha
      helix. The PagP barrel axis is tilted by 25 degrees with respect to the membrane
      normal. An interior hydrophobic pocket in the outer leaflet-exposed half of the
      molecule functions as a hydrocarbon ruler that allows the enzyme to distinguish
      palmitate from other acyl chains found in phospholipids. Internalization of a
      phospholipid palmitoyl group within the barrel appears to occur by lateral
      diffusion from the outer leaflet through non-hydrogen-bonded regions between beta
      strands. The MsbA-dependent trafficking of lipids from the inner membrane to the
      outer membrane outer leaflet is necessary for lipid A palmitoylation in vivo. The
      mechanisms by which bacteria regulate pagP gene expression strikingly reflect the
      corresponding pathogenic lifestyle of the bacterium. Variations on PagP structure
      and function can be illustrated with the known homologues from Gram-negative
      bacteria, which include pathogens of humans and other mammals in addition to
      pathogens of insects and plants. The PagP enzyme is potentially a target for the
      development of anti-infective agents, a probe of outer membrane lipid asymmetry,
      and a tool for the synthesis of lipid A-based vaccine adjuvants and endotoxin
      antagonists.

PMID- 16091034
TI  - pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and
      artemisinin sensitivity in Plasmodium falciparum.
AB  - The emergence and spread of multidrug resistant Plasmodium falciparum has
      severely limited the therapeutic options for the treatment of malaria. With ever
      increasing failure rates associated with chloroquine or sulphadoxine
      pyrimethamine treatment, attention has turned to the few alternatives, which
      include quinine and mefloquine. Here, we have investigated the role of pfmdr1 3'
      coding region point mutations in antimalarial drug susceptibility by allelic
      exchange in the GC03 and 3BA6 parasite lines. Results with pfmdr1-recombinant
      clones indicate a significant role for the N1042D mutation in contributing to
      resistance to quinine and its diastereomer quinidine. The triple mutations
      S1034C/N1042D/D1246Y, highly prevalent in South America, were also found to
      enhance parasite susceptibility to mefloquine, halofantrine and artemisinin.
      pfmdr1 3' mutations showed minimal effect on P. falciparum resistance to
      chloroquine or its metabolite mono-desethylchloroquine in these parasite lines,
      in contrast to previously published results obtained with 7G8 parasites. This
      study supports the hypothesis that pfmdr1 3' point mutations can significantly
      affect parasite susceptibility to a wide range of antimalarials in a strain
      specific manner that depends on the parasite genetic background.

PMID- 16091035
TI  - Mutagenesis of PepA suggests a new model for the Xer/cer synaptic complex.
AB  - PepA is an aminopeptidase and also functions as a DNA-binding protein in two
      unrelated systems in Escherichia coli: Xer site-specific recombination and
      transcriptional regulation of carAB. In these systems, PepA binds to and brings
      together distant segments of DNA to form interwrapped, nucleosome-like
      structures. Here we report the selection of PepA mutants that were unable to
      support efficient Xer recombination. These mutants were defective in DNA-binding
      and in transcriptional regulation of carAB, but had normal peptidase activity.
      The mutations define extended patches of basic residues on the surface of the N
      terminal domain of PepA that flank a previously proposed DNA-binding groove in
      the C-terminal domain of PepA. Our results suggest that DNA passes through this C
      terminal groove in the PepA hexamer, and is bound by N-terminal DNA-binding
      determinants at each end of the groove. Based on our data, we propose a new model
      for the Xer synaptic complex, in which two recombination sites are wrapped around
      a single hexamer of PepA, bringing the cross-over sites together for strand
      exchange by the Xer recombinases. In this model, PepA stabilizes negative
      plectonemic interwrapping between two segments of DNA by passing one segment
      through the C-terminal groove while the other is held in place in a loop over the
      groove.

PMID- 16091036
TI  - Cell cycle arrest during S or M phase generates polarized growth via distinct
      signals in Candida albicans.
AB  - Treatments that perturb DNA synthesis or mitosis will activate checkpoints that
      prevent cell cycle progression and cell proliferation. In yeast-form cells of the
      fungal pathogen Candida albicans, exposure to hydroxyurea (HU) or shutting off
      expression of the polo-like kinase CaCDC5 blocked nuclear division and spindle
      elongation, but activated a highly polarized growth mode. We have used
      transcription profiling both to characterize the initiation and progression of
      this polar growth pattern and to determine how cell elongation may be linked to
      the cell cycle in C. albicans. Different gene expression patterns during early
      stages of cell elongation support the concept that CaCdc5p-depleted and HU
      exposed cells were blocked at different stages of the cell cycle, and suggest
      that different signals may generate the common polarized growth phenotype.
      Consistent with this, BUB2 expression was modulated in CaCdc5p-depleted cells,
      and absence of BUB2 prevented the maintenance of cell polarization, resulting in
      multibudded, pseudohyphal cells with constrictions. In contrast, HU-induced
      filaments did not modulate or require BUB2, but were dependent on the GTPase
      Ras1p. However, at later stages of cell elongation, transcription profiles were
      more similar, and comparisons with serum-induced hyphae revealed that the cell
      cycle-arrested filaments expressed several targets of the hyphal signalling
      pathways. Thus, arresting the yeast cell cycle in S or M phase generates a
      polarized growth pattern through different mechanisms in C. albicans, and
      maintenance of the polar growth mode can ultimately lead to the expression of
      hyphal-associated cell wall and virulence-related factors, in the absence of any
      external stimuli.

PMID- 16091037
TI  - LuxS controls bacteriocin production in Streptococcus mutans through a novel
      regulatory component.
AB  - The oral pathogen Streptococcus mutans employs a variety of mechanisms to
      maintain a competitive advantage over many other oral bacteria which occupy the
      same ecological niche. Production of the bacteriocin, mutacin I, is one such
      mechanism. However, little is known about the regulatory mechanisms associated
      with mutacin I production. Previous work has demonstrated that the production of
      mutacin I greatly increased with cell density. In this study, we found that high
      cell density also triggered high level mutacin I gene transcription. However,
      this response was abolished upon deletion of luxS. Further analysis using real
      time reverse transcription polymerase chain reaction (RT-PCR) demonstrated that
      in the luxS mutant transcription of both the mutacin I structural gene mutA and
      the mutacin I transcriptional activator mutR was impaired. Through microarray
      analysis, a putative transcription repressor annotated as Smu1274 in the Los
      Alamos National Laboratory Oral Pathogens Sequence Database was identified, which
      was strongly induced in the luxS mutant. Characterization of Smu1274, which we
      referred to as irvA, suggested that it may act as an inducible repressor to
      suppress mutacin I gene expression. A luxS and irvA double mutant regained the
      ability to produce mutacin I; whereas a constitutive irvA-producing strain was
      impaired in mutacin I production. These findings reveal a novel regulatory
      pathway for mutacin I gene expression, which may provide clues to the regulatory
      mechanisms of other cellular functions regulated by luxS in S. mutans.

PMID- 16091038
TI  - Selection and characterization of Yersinia pestis YopN mutants that
      constitutively block Yop secretion.
AB  - Secretion of Yop effector proteins by the Yersinia pestis plasmid pCD1-encoded
      type III secretion system (T3SS) is regulated in response to specific
      environmental signals. Yop secretion is activated by contact with a eukaryotic
      cell or by growth at 37 degrees C in the absence of calcium. The secreted YopN
      protein, the SycN/YscB chaperone and TyeA form a cytosolic YopN/SycN/YscB/TyeA
      complex that is required to prevent Yop secretion in the presence of calcium and
      prior to contact with a eukaryotic cell. The mechanism by which these proteins
      prevent secretion and the subcellular location where the block in secretion
      occurs are not known. To further investigate both the mechanism and location of
      the YopN-dependent block, we isolated and characterized several YopN mutants that
      constitutively block Yop secretion. All the identified amino-acid substitutions
      that resulted in a constitutive block in Yop secretion mapped to a central domain
      of YopN that is not directly involved in the interaction with the SycN/YscB
      chaperone or TyeA. The YopN mutants required an intact TyeA-binding domain and
      TyeA to block secretion, but did not require an N-terminal secretion signal, an
      intact chaperone-binding domain or the SycN/YscB chaperone. These results suggest
      that a C-terminal domain of YopN complexed with TyeA blocks Yop secretion from a
      cytosolic, not an extracellular, location. A hypothetical model for how the
      YopN/SycN/YscB/TyeA complex regulates Yop secretion is presented.

PMID- 16091039
TI  - Paralysis and killing of Caenorhabditis elegans by enteropathogenic Escherichia
      coli requires the bacterial tryptophanase gene.
AB  - Pathogenic Escherichia coli, including enteropathogenic E. coli (EPEC),
      enterohaemorrhagic E. coli (EHEC), enteroinvasive E. coli (EIEC) and
      enterotoxigenic E. coli (ETEC) are major causes of food and water-borne disease.
      We have developed a genetically tractable model of pathogenic E. coli virulence
      based on our observation that these bacteria paralyse and kill the nematode
      Caenorhabditis elegans. Paralysis and killing of C. elegans by EPEC did not
      require direct contact, suggesting that a secreted toxin mediates the effect.
      Virulence against C. elegans required tryptophan and bacterial tryptophanase, the
      enzyme catalysing the production of indole and other molecules from tryptophan.
      Thus, lack of tryptophan in growth media or deletion of tryptophanase gene failed
      to paralyse or kill C. elegans. While known tryptophan metabolites failed to
      complement an EPEC tryptophanase mutant when presented extracellularly,
      complementation was achieved with the enzyme itself expressed either within the
      pathogen or within a cocultured K12 strains. Thus, an unknown metabolite of
      tryptophanase, derived from EPEC or from commensal non-pathogenic strains,
      appears to directly or indirectly regulate toxin production within EPEC. EPEC
      strains containing mutations in the locus of enterocyte effacement (LEE), a
      pathogenicity island required for virulence in humans, also displayed attenuated
      capacity to paralyse and kill nematodes. Furthermore, tryptophanase activity was
      required for full activation of the LEE1 promoter, and for efficient formation of
      actin-filled membranous protrusions (attaching and effacing lesions) that form on
      the surface of mammalian epithelial cells following attachment and which depends
      on LEE genes. Finally, several C. elegans genes, including hif-1 and egl-9,
      rendered C. elegans less susceptible to EPEC when mutated, suggesting their
      involvement in mediating toxin effects. Other genes including sek-1, mek-1, mev
      1, pgp-1,3 and vhl-1, rendered C. elegans more susceptible to EPEC effects when
      mutated, suggesting their involvement in protecting the worms. Moreover we have
      found that C. elegans genes controlling lifespan (daf-2, age-1 and daf-16), also
      mediate susceptibility to EPEC. Together, these data suggest that this C.
      elegans/EPEC system will be valuable in elucidating novel factors relevant to
      human disease that regulate virulence in the pathogen or susceptibility to
      infection in the host.

PMID- 16091040
TI  - A tertiary structural element in S box leader RNAs is required for S
      adenosylmethionine-directed transcription termination.
AB  - The S box transcription termination control system regulates expression of genes
      involved in methionine metabolism. Expression of the S box regulon, comprised of
      11 transcriptional units in Bacillus subtilis, is induced in response to
      starvation for methionine. We previously demonstrated that S-adenosylmethionine
      (SAM) is the molecular effector sensed by the S box leader RNAs during
      transcription. A secondary structure model for S box leader RNAs was developed
      based on conservation of primary sequence elements and sequence covariation in
      helical domains. Covariation of nucleotides in two distantly spaced unpaired
      regions in the S box leader RNAs suggested that these two domains might interact
      in the RNA tertiary structure. In this study, site-directed mutagenesis of the
      covarying residues in two B. subtilis S box leader sequences was employed to test
      the hypothesis that base-pairing between these regions may be important. The
      effect of these mutations on in vivo expression, transcription termination in
      vitro, SAM binding, and leader RNA structure strongly supported the model that
      interaction between these two regions plays a key role in S box leader function.
      This provides the first insight into the three-dimensional arrangement of
      structural elements within the S box RNAs.

PMID- 16091041
TI  - Identification of a fibronectin-binding domain within the Campylobacter jejuni
      CadF protein.
AB  - The binding of Campylobacter jejuni to fibronectin (Fn), a component of the
      extracellular matrix, is mediated by a 37 kDa outer membrane protein termed CadF
      for Campylobacter adhesion to Fn. Previous studies have indicated that C. jejuni
      binds to Fn on the basolateral surface of T84 human colonic cells. To further
      characterize the interaction of the CadF protein with Fn, enzyme-linked
      immunosorbent assays were performed to identify the Fn-binding domain (Fn-BD).
      Using overlapping 30-mer and 16-mer peptides derived from translated cadF
      nucleotide sequence, maximal Fn-binding activity was localized to four amino
      acids (AA 134-137) consisting of the residues phenylalanine-arginine-leucine
      serine (FRLS). A mouse alpha-CadF peptide polyclonal antibody (M alpha-CadF
      peptide pAb) was generated using FRLS containing peptides and found to react with
      viable C. jejuni as judged by indirect fluorescent microscopy, suggesting that
      the FRLS residues are surface-exposed. Binding of CadF to purified Fn and INT 407
      human epithelial cells was significantly inhibited with peptides containing the
      Fn-BD. Moreover, a CadF recombinant variant protein, in which the Phe-Arg-Leu
      residues (CadF AA 134-136) were altered to Ala-Ala-Gly, exhibited a 91% decrease
      in Fn-binding activity as compared with the wild-type CadF protein. Collectively,
      these data indicate that the FRLS residues (CadF AA 134-137) of the C. jejuni
      CadF protein possess Fn-binding activity.

PMID- 16091042
TI  - A symbiosis expressed non-ribosomal peptide synthetase from a mutualistic fungal
      endophyte of perennial ryegrass confers protection to the symbiotum from insect
      herbivory.
AB  - While much is known about the biosynthesis of secondary metabolites by
      filamentous fungi their biological role is often less clear. The assumption is
      these pathways have adaptive value to the organism but often the evidence to
      support this role is lacking. We provide the first genetic evidence that the
      fungal produced secondary metabolite, peramine, protects a host plant from insect
      herbivory. Peramine is a potent insect feeding deterrent synthesized by
      Epichloe/Neotyphodium mutualistic endophytes in association with their grass
      hosts. The structure of peramine, a pyrrolopyrazine, suggests that it is the
      product of a reaction catalysed by a two-module non-ribosomal peptide synthetase
      (NRPS). Candidate sequences for a peramine synthetase were amplified by reverse
      transcription polymerase chain reaction. Four unique NRPS products were
      identified, two of which were preferentially expressed in planta. One of these
      hybridized to known peramine producing strains. This clone was used to isolate an
      Epichloe festucae cosmid that contained a two-module NRPS, designated perA. Nine
      additional genes, which show striking conservation of microsynteny with Fusarium
      graminearum and other fungal genomes, were identified on the perA-containing
      cosmid. Associations between perennial ryegrass and an E. festucae mutant deleted
      for perA lack detectable levels of peramine. A wild-type copy of perA
      complemented the deletion mutant, confirming that perA is a NRPS required for
      peramine biosynthesis. In a choice bioassay, plant material containing the perA
      mutant was as susceptible to Argentine stem weevil (ASW) (Listronotus
      bonariensis) feeding damage as endophyte-free plants confirming that peramine is
      the E. festucae metabolite responsible for ASW feeding deterrent activity.

PMID- 16091043
TI  - Frp1 is a Fusarium oxysporum F-box protein required for pathogenicity on tomato.
AB  - Fusarium oxysporum f. sp. lycopersici is the causal agent of tomato wilt disease.
      In order to identify genes involved in its pathogenicity, we performed
      insertional mutagenesis. Mutant N40 had lost its pathogenicity completely, when
      tested in bioassays with tomato seedlings. Molecular characterization of mutant
      N40 revealed that the plasmid insertion had occurred in a gene that codes for a
      60.2 kDa protein containing an F-box motif. The gene was therefore designated as
      FRP1 (F-box protein required for pathogenicity). Targeted FRP1 disruptants had
      lost their pathogenicity completely, and became fully virulent again upon re
      introduction of the FRP1 gene. This confirmed that the FRP1 gene is required for
      pathogenesis. In a yeast two-hybrid assay Frp1 interacts with Skp1, suggesting
      involvement of an SCF ubiquitin ligase complex in pathogenicity. FRP1 is
      constitutively expressed during infection and under different culture conditions.
      Although growth, spore formation and germination on artificial media were not
      impaired, confocal laser scanning microscopy of a GFP-marked mutant N40 and a GFP
      marked targeted FRP1 disruptant revealed that they were unable to colonize the
      roots.

PMID- 16091044
TI  - A new mechanism for chloramphenicol, florfenicol and clindamycin resistance:
      methylation of 23S ribosomal RNA at A2503.
AB  - The gene product of cfr from Staphylococcus sciuri confers resistance to
      chloramphenicol, florfenicol and clindamycin in Staphylococcus spp. and
      Escherichia coli. Cfr is not similar to any other known chloramphenicol
      resistance determinant. Comparative investigation of E. coli with and without a
      plasmid-encoded Cfr showed a decreased drug binding to ribosomes in the presence
      of Cfr. As chloramphenicol/florfenicol and clindamycin have partly overlapping
      drug binding sites on the ribosome, the most likely explanation is that Cfr
      modifies the RNA in the drug binding site. This hypothesis was supported by drug
      footprinting data that showed both a decreased drug binding and an enhanced
      reverse transcriptase stop at position 2504, which corresponds to a modification
      at position A2503 at the drug binding site. A 45 n long RNA fragment containing
      the appropriate region was isolated and MALDI-TOF mass spectrometry in
      combination with tandem mass spectrometry showed an additional methylation at
      position A2503. Moreover, reduced methylation was detected at nucleotide C2498.
      The results show that Cfr is an RNA methyltransferase that targets nucleotide
      A2503 and inhibits ribose methylation at nucleotide C2498, thereby causing
      resistance to chloramphenicol, florfenicol and clindamycin.

PMID- 16091045
TI  - Localization of RecA in Escherichia coli K-12 using RecA-GFP.
AB  - RecA is important in recombination, DNA repair and repair of replication forks.
      It functions through the production of a protein-DNA filament. To study the
      localization of RecA in live Escherichia coli cells, the RecA protein was fused
      to the green fluorescence protein (GFP). Strains with this gene have
      recombination/DNA repair activities three- to tenfold below wild type (or about
      1000-fold above that of a recA null mutant). RecA-GFP cells have a background of
      green fluorescence punctuated with up to five foci per cell. Two types of foci
      have been defined: 4,6-diamidino-2-phenylindole (DAPI)-sensitive foci that are
      bound to DNA and DAPI-insensitive foci that are DNA-less aggregates/storage
      structures. In log phase cells, foci were not localized to any particular region.
      After UV irradiation, the number of foci increased and they localized to the cell
      centre. This suggested colocalization with the DNA replication factory. recA,
      recB and recF strains showed phenotypes and distributions of foci consistent with
      the predicted effects of these mutations.

PMID- 16091046
TI  - Dps/Dpr ferritin-like protein: insights into the mechanism of iron incorporation
      and evidence for a central role in cellular iron homeostasis in Streptococcus
      suis.
AB  - The Dps family members constitute a distinct group of multimeric and ferritin
      like iron binding proteins (up to 500 iron atoms/12-mer) that are widespread in
      eubacteria and archaea and implicated in oxidative stress resistance and
      virulence. Despite the wealth of structural knowledge, the mechanism of iron
      incorporation has remained elusive. Here, we provide evidence on Dpr of the swine
      and human pathogen Streptococcus suis that: (i) iron incorporation proceeds by
      Fe(II) binding, Fe(II) oxidation and subsequent storage as Fe(III); (ii) Fe(II)
      atoms enter the 12-mer cavity through four hydrophilic pores; and (iii) Fe(II)
      atoms are oxidized inside the 12-mer cavity at 12 identical inter-subunit sites,
      which are structurally different but functionally equivalent to the ferroxidase
      centres of classical ferritins. We also provide evidence, by deleting and
      ectopically overexpressing Dpr, that Dpr affects cellular iron homeostasis. The
      key residues responsible for iron incorporation in S. suis Dpr are well conserved
      throughout the Dps family. A model for the iron incorporation mechanism of the
      Dps/Dpr ferritin-like protein is proposed.

PMID- 16091047
TI  - The crystal structures of Lactococcus lactis MG1363 Dps proteins reveal the
      presence of an N-terminal helix that is required for DNA binding.
AB  - Dps proteins play a major role in the protection of bacterial DNA from damage by
      reactive oxygen species. Previous studies have implicated the extended lysine
      containing N-terminal regions of Dps subunits in DNA binding, but this part of
      the structure has not previously been observed crystallographically. Here the
      structures of two Dps proteins (DpsA and DpsB) from Lactococcus lactis MG1363
      reveal for the first time the presence of an N-terminal alpha helix that extends
      from the core of the Dps subunit. Consequently, the N-terminal helices are
      displayed in parallel pairs on the exterior of the dodecameric Dps assemblies.
      Both DpsA and DpsB bind DNA. Deletion of the DpsA N-terminal helix impaired DNA
      binding. The N-terminal Lys residues of Escherichia coli Dps have been implicated
      in DNA binding. Replacement of the lactococcal DpsA Lys residues 9, 15 and 16 by
      Glu did not inhibit DNA binding. However, DNA binding was inhibited by EDTA,
      suggesting a role for cations in DNA binding. In contrast to E. coli, Bacillus
      brevis and Mycobacterium smegmatis Dps:DNA complexes, in which DNA interacts with
      crystalline Dps phases, L. lactis DNA:Dps complexes appeared as non-crystalline
      aggregates of protein and DNA in electron micrographs.

PMID- 16091048
TI  - Identification and structural characterization of an unusual mycobacterial
      monomeromycolyl-diacylglycerol.
AB  - Systematic thin layer chromatographic (TLC) analysis of apolar lipids in
      Mycobacterium kansasii revealed the presence of a previously uncharacterized
      novel component. The product was ubiquitously found in a panel of M. kansasii
      clinical isolates, as well as other pathogenic and non-pathogenic mycobacterial
      species. TLC analysis of [(14)C]-acetate- or [(14)C]-glycerol-labelled M.
      kansasii cultures tentatively assigned the novel product as an unusual
      triacylglycerol-related lipid. Subsequent purification, followed by structural
      determination using (1)H-nuclear magnetic resonance (NMR) and electrospray mass
      spectrometry (ES/MS), led to the identification of this product as a
      monomeromycolyl-diacylglycerol (MMDAG). Treatment of M. kansasii with either
      isoniazid (INH), a well-known type II fatty acid synthase (FAS-II) and mycolic
      acid biosynthesis inhibitor, or tetrahydrolipstatin (THL), a drug approved for
      treating obesity, correlated with a reduced incorporation of [(14)C]-acetate into
      both mycolic acids and MMDAG. Addition of INH or THL to the cultures induced
      major morphological changes and, surprisingly, resulted in an increased number of
      lipid storage bodies, as determined by electron microscopy. The potent
      antimycobacterial activity of THL was confirmed against a variety of
      mycobacterial species, including INH-susceptible and -resistant Mycobacterium
      tuberculosis strains. Therefore, THL and other beta-lactones may be promising
      drugs for the development of new antitubercular therapy.

PMID- 16091049
TI  - The conserved flaF gene has a critical role in coupling flagellin translation and
      assembly in Caulobacter crescentus.
AB  - The expression of the flagellin proteins in Caulobacter crescentus is regulated
      by the progression of flagellar assembly both at the transcriptional and post
      transcriptional levels. An early basal body structure is required for the
      transcription of flagellin genes, whereas the ensuing assembly of a hook
      structure is required for flagellin protein synthesis. Previous experiments have
      shown that the negative regulatory protein, FlbT, operates this second post
      transcriptional checkpoint by associating with the 5' untranslated region (UTR)
      of the fljK flagellin transcript, inhibiting translation and destabilizing the
      mRNA. In this paper we examine the role of flaF in flagellar biogenesis. The flaF
      gene, which is conserved in several speices of flagellated alpha-proteobacteria,
      is required for motility and flagellin protein synthesis. A deletion of flbT in a
      DeltaflaF strain restored flagellin protein expression, but not motility,
      indicating that FlaF functions in filament assembly. Mutant strains with a
      deletion in flaF had no detectable fljK mRNA, the levels of which were restored
      by an additional mutation in flbT. Assay of fljK gene expression using
      transcription and translation reporter fusions indicated that FlaF was essential
      for the translation of fljK mRNA. FlaF protein levels were under cell cycle
      control, peaking during the period of flagellin expression and filament assembly,
      whereas FlbT was present throughout the cell cycle. These results suggest that
      FlbT and FlaF activities oppose one another in the regulation of flagellin
      expression in response to both the progression of flagellar assembly and the cell
      cycle.

PMID- 16091050
TI  - Defining the genetic differences between wild and domestic strains of Bacillus
      subtilis that affect poly-gamma-dl-glutamic acid production and biofilm
      formation.
AB  - Biofilms are communities of microbial cells that are encased in a self-produced,
      polymeric matrix and are adherent to a surface. For several species of bacteria,
      an enhanced ability to form biofilms has been linked with an increased capability
      to produce exopolymers. To identify exopolymers of Bacillus subtilis that can
      contribute to biofilm formation, we transferred the genetic determinants that
      control exopolymer production from a wild, exopolymer-positive strain to a
      domesticated, exopolymer-negative strain. Mapping these genetic determinants led
      to the identification of gamma-poly-dl-glutamic acid (gamma-PGA) as an exopolymer
      that increases biofilm formation, possibly through enhancing cell-surface
      interactions. Production of gamma-PGA by Bacillus subtilis was known to be
      dependent on the two-component regulator ComPA; this study highlighted the
      additional dependence on the DegS-DegU, DegQ and SwrA regulator proteins. The
      inability of the domestic strain of B. subtilis to produce gamma-PGA was mapped
      to two base pairs; a single base pair change in the promoter region of degQ and a
      single base pair insertion in the coding region of swrA. Introduction of alleles
      of degQ and swrA from the wild strain into the domestic strain was sufficient to
      allow gamma-PGA production. In addition to controlling gamma-PGA production,
      ComPA and DegSU were also shown to activate biofilm formation through an as yet
      undefined pathway. The identification of these regulators as affecting gamma-PGA
      production and biofilm formation suggests that these processes are regulated by
      osmolarity, high cell density and phase variation.

PMID- 16091051
TI  - Conservation of genes and processes controlled by the quorum response in
      bacteria: characterization of genes controlled by the quorum-sensing
      transcription factor ComA in Bacillus subtilis.
AB  - Quorum or diffusion responses in bacteria are mediated by secreted signalling
      molecules that accumulate extracellularly as cultures grow to high density. The
      regulatory response to these signalling molecules can result in dramatic changes
      in gene expression. In Bacillus subtilis, a quorum response is mediated by a
      secreted 10-amino-acid modified peptide (ComX pheromone) that activates a
      receptor histidine kinase (ComP) that activates a response regulator
      transcription factor (ComA). We have used DNA microarrays to identify genes
      controlled by the ComX-ComP-ComA quorum-sensing pathway. We found that ComX, ComP
      and ComA affect the same set of genes, indicating that the kinase ComP is the
      only receptor for the signalling molecule ComX, and that ComA is the only
      transcription factor activated directly by ComP, under the conditions tested.
      Expression of over 20 genes appears to be controlled directly by this signalling
      pathway, and expression of over 150 additional genes, including those involved in
      competence development, appears to be controlled indirectly. The genes affected
      appear to have three general functions: (i) to co-ordinate physiological changes
      involved in developmental pathways, (ii) to produce extracellular products under
      conditions in which high concentrations of product are needed to be effective and
      (iii) to enhance survival, growth and colonization under conditions of crowding
      or limited diffusion. Many of the genes and processes controlled by the quorum
      response in B. subtilis are also regulated by quorum sensing in Gram-positive and
      Gram-negative bacteria. The quorum-sensing signalling molecules and regulatory
      proteins are quite different between Gram-positives and Gram-negatives and the
      convergent physiological regulation of similar genes and processes indicate the
      important and conserved nature of the quorum response.

PMID- 16091053
TI  - Systematic review and meta-analysis: proton-pump inhibitor treatment for ulcer
      bleeding reduces transfusion requirements and hospital stay--results from the
      Cochrane Collaboration.
AB  - BACKGROUND: Proton-pump inhibitors reduce re-bleeding and surgical intervention,
      but not mortality, after ulcer bleeding. AIM: To examine the effects of proton
      pump inhibitor treatment on transfusion requirements and length of hospital stay
      in patients with ulcer bleeding. METHODS: For the Cochrane Collaboration meta
      analysis of randomized-controlled trials of proton-pump inhibitor therapy for
      ulcer bleeding, outcomes of transfusion requirements and hospital stay were
      summarized, respectively, as mean (+/-s.d.) units transfused and hospital days.
      We calculated weighted mean difference with 95% confidence interval. We also
      performed subgroup analyses according to geographical origin of the randomized
      controlled trials. RESULTS: There was significant heterogeneity among randomized
      controlled trials for either outcome. Overall, proton-pump inhibitor treatment
      marginally reduced transfusion requirements (WMD = -0.6 units; 95% CI: -1.1 to 0;
      P = 0.05) and length of hospitalization (WMD = -1.1 days; 95% CI: -1.5 to -0.7; P
      < 0.0001). Most of the randomized-controlled trials did not state precise
      criteria for administering blood transfusion and discharging patients, thereby
      limiting the strength of conclusions on the pooled effects. CONCLUSIONS: Proton
      pump inhibitor treatment for ulcer bleeding produces small, but potentially
      important, reductions in transfusion requirements and length of hospitalization.

PMID- 16091054
TI  - Does concurrent prescription of selective serotonin reuptake inhibitors and non
      steroidal anti-inflammatory drugs substantially increase the risk of upper
      gastrointestinal bleeding?
AB  - BACKGROUND: A 15-fold increased risk of gastrointestinal bleeding has been
      reported with concurrent use of selective serotonin reuptake inhibitors and non
      steroidal anti-inflammatory drugs. Recent guidance cautions against concurrent
      prescription, particularly in older people. AIM: To quantify the risk of
      gastrointestinal bleeding associated with current exposure to non-steroidal anti
      inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs
      concurrently. METHODS: We conducted a case-control analysis of 11,261 cases with
      upper gastrointestinal bleeding and 53,156 controls matched by gender, age and
      general practice from computerized primary care data. We coupled this with self
      controlled case series analysis. RESULTS: Both drugs were associated with a
      twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95%
      confidence interval 2.08-2.72 for selective serotonin reuptake inhibitors and
      odds ratio = 2.15, 95% confidence interval 2.02-2.28 for non-steroidal anti
      inflammatory drugs). This increased risk was marginally higher for concurrent
      prescription (odds ratio = 2.93, 95% confidence interval 2.25-3.82). The self
      controlled analysis showed a greater incidence rate ratio for gastrointestinal
      bleeding with non-steroidal anti-inflammatory drugs (2.71, 95% confidence
      interval 2.51-2.91) and lower incidence rate ratio with selective serotonin
      reuptake inhibitors (1.71, 95% confidence interval 1.48-1.98). The incidence rate
      ratio when both drugs were combined was 3.25, 95% confidence interval 1.95-5.42.
      Estimates were similar after restricting to people over 80 years of age.
      Increased risk of gastrointestinal bleeding was not specifically related to class
      of non-steroidal anti-inflammatory drugs and was similar when we looked at
      tricyclic anti-depressants. CONCLUSIONS: Our study suggests that the risk of
      gastrointestinal bleeding is not substantially increased when non-steroidal anti
      inflammatory drugs and selective serotonin reuptake inhibitors are prescribed
      together, compared with their use alone.

PMID- 16091055
TI  - Daily treatment with esomeprazole is superior to that taken on-demand for
      maintenance of healed erosive oesophagitis.
AB  - BACKGROUND: On-demand therapy with esomeprazole is effective for long-term
      treatment of non-erosive gastro-oesophageal reflux disease, but it has not been
      evaluated in erosive gastro-oesophageal reflux disease. AIMS: To compare
      endoscopic and symptomatic remission over a 6-month period when patients with
      healed erosive gastro-oesophageal reflux disease are treated with esomeprazole 20
      mg, either once daily or on-demand. METHODS: Patients with verified erosive
      reflux oesophagitis of Los Angeles grades A-D were enrolled. Following 4-8 weeks
      treatment with esomeprazole 40 mg daily, those who were endoscopically healed and
      had symptom control during the last week were randomized to maintenance therapy
      for 6 months with esomeprazole 20 mg, taken either once daily or on-demand.
      RESULTS: Of 539 enrolled patients, 494 (91%) were healed at 8 weeks and 477 were
      randomized to maintenance therapy with esomeprazole 20 mg, 243 once daily and 234
      on-demand. After once daily treatment, 81% of patients were still in remission at
      6 months, compared with only 58% who took on-demand treatment (P < 0.0001). A
      difference in remission was found irrespective of baseline grade of oesophagitis,
      but it was more pronounced for the more severe grades. There was no difference in
      overall symptomatic remission between the two treatments, although heartburn was
      significantly more prevalent in the on-demand group. CONCLUSIONS: Once daily
      esomeprazole 20 mg was better than that taken on-demand for maintaining healed
      erosive oesophagitis, regardless of baseline Los Angeles grade.

PMID- 16091056
TI  - Long-term prevention of erosive or ulcerative gastro-oesophageal reflux disease
      relapse with rabeprazole 10 or 20 mg vs. placebo: results of a 5-year study in
      the United States.
AB  - BACKGROUND: Erosive gastro-oesophageal reflux disease (GERD) is a chronic
      condition requiring long-term maintenance treatment. However, few trials of
      proton pump inhibitors in maintaining healing of erosive or ulcerative GERD are
      conducted for longer than 1 year. AIM: To compare the efficacy and safety of 10-
      and 20-mg rabeprazole with placebo in the 5-year maintenance of healing in
      patients previously diagnosed with erosive/ulcerative GERD healed in an acute
      efficacy trial. METHODS: Patients (N = 497) were randomized to receive once-daily
      doses of 10- or 20-mg rabeprazole or placebo. The primary efficacy measure was
      endoscopically documented absence of oesophageal erosions or ulcerations.
      RESULTS: After 5 years, relapse rates in both rabeprazole groups were
      significantly lower than with placebo (rabeprazole 20 mg, 11%; 10 mg, 23%;
      placebo, 63%; P < 0.001 for rabeprazole vs. placebo; P = 0.005 for rabeprazole 20
      mg vs. 10 mg). Both rabeprazole doses were significantly superior to placebo in
      preventing relapse of heartburn frequency and improving patient quality of life.
      Analyses of adverse events, biopsy findings and laboratory values showed no
      evidence of clinically significant effects. CONCLUSIONS: Five-year maintenance
      therapy with rabeprazole is effective in preventing relapse of erosive or
      ulcerative GERD and is well tolerated.

PMID- 16091057
TI  - Low-dose oral microemulsion ciclosporin for severe, refractory ulcerative
      colitis.
AB  - BACKGROUND: The optimal modalities of treatment with oral microemulsion
      ciclosporin in patients with severe, steroid-refractory ulcerative colitis are
      uncertain. AIM: To assess the applicability, in terms of efficacy and
      tolerability, of a standard oral microemulsion ciclosporin treatment protocol
      targeting relatively low blood ciclosporin concentrations, in patients with
      severe, steroid-resistant ulcerative colitis. PATIENTS AND METHODS: Patients with
      a severe attack of ulcerative colitis and no satisfactory response to intravenous
      corticosteroids were started on oral microemulsion ciclosporin. Dosages were
      adapted according to a standard protocol, targeting a blood predose ciclosporin
      concentration (C0) of 100-200 ng/mL. Patients without a clinical response on day
      8 were scheduled for colectomy. RESULTS: Sixteen patients were enrolled. A
      clinical response was observed in 14/16 (88%). The mean clinical activity index
      scores and concentrations of C-reactive protein on days 0, 4 and 8 were 11.8, 6.7
      and 4.1, and 50.3, 19.3 and 9.7 mg/L respectively. The mean C0 (days 0-8) was 149
      pg/mL. The mean creatinine clearance rates on days 0 and 8 were 88 and 96 mL/min.
      One patient had an acute elevation of transaminases that resulted in
      discontinuing ciclosporin. CONCLUSIONS: Even when dosed for a target C0 of 100
      200 ng/mL, oral microemulsion ciclosporin for severe, steroid-refractory
      ulcerative colitis achieves an efficacy similar to that attained with higher,
      potentially more toxic levels. The oral route should replace intravenous
      treatment in this clinical setting.

PMID- 16091058
TI  - Is interferon-alpha therapy safe and effective for patients with chronic
      hepatitis C and inflammatory bowel disease? A case-control study.
AB  - BACKGROUND: Hepatitis C virus infection is more common in patients with
      inflammatory bowel disease than in general population. Limited data are available
      as to the safety and efficacy of alpha-interferon therapy for chronic active
      hepatitis C in patients with concomitant inflammatory bowel disease. AIM: To
      evaluate the efficacy and safety of alpha-interferon monotherapy in patients with
      chronic active hepatitis C and inactive or mildly active inflammatory bowel
      disease. METHODS: A total of 513 consecutive inflammatory bowel disease patients
      at a single centre were tested for antibodies to hepatitis C virus (anti
      hepatitis C virus) between 1995 and 2000. Twenty-one patients had detectable anti
      hepatitis C virus Ab and were hepatitis C virus-RNA positive with histologically
      proved chronic active hepatitis. Each of these patients, whose inflammatory bowel
      disease was in clinical remission or mildly active, was sex- and age-matched to
      three controls with similar histological grade and stage of chronic hepatitis C
      virus but without inflammatory bowel disease; and all were treated with human
      leucocyte alpha-interferon 6 million units given thrice weekly for 12 months.
      Responses to treatment were classified as follows: complete response-
      persistently normal alanine aminotransferase and viral clearance (hepatitis C
      virus-RNA-ve) at the end-of-treatment, incomplete response--alanine
      aminotransferase normalization without viral clearance (hepatitis C virus
      RNA+ve), and sustained response--alanine aminotransferase normalization and
      hepatitis C virus clearance 12 months after the end-of-treatment. RESULTS: Twenty
      one patients with chronic active hepatitis C and inflammatory bowel disease (10
      with Crohn's disease and 11 with ulcerative colitis) and 63 sex- and age-matched
      controls with chronic hepatitis C virus alone received alpha-interferon
      monotherapy. Response rates to interferon were similar for inflammatory bowel
      disease patients compared with controls [CR 42% vs. 35% and SR 24% vs. 18% (P,
      not significant), respectively]. None of the 21 inflammatory bowel disease
      patients had severe adverse effects and the mild ones observed were comparable
      with those seen in the control group. No patients developed an inflammatory bowel
      disease relapse during the interferon treatment period or in the 12 months
      thereafter. CONCLUSIONS: The biochemical and virological response to a 12-month
      human leucocyte alpha-interferon treatment in patients with chronic active
      hepatitis C are similar to that observed in matched controls with chronic
      hepatitis C virus without inflammatory bowel disease. Adverse effects are similar
      in both groups of patients and unrelated to the underlying inflammatory bowel
      condition. This provides hepatologists with evidence that alpha-interferon can be
      safely administered to patients with chronic hepatitis C virus and inflammatory
      bowel disease provided that the inflammatory bowel condition is in clinical
      remission.

PMID- 16091059
TI  - alpha-fetoprotein response predicts survival benefits of thalidomide in advanced
      hepatocellular carcinoma.
AB  - BACKGROUND: Radiographic measurements do not always reflect the biological
      response of hepatocellular carcinoma to drug therapy. AIMS: To evaluate the
      clinical implications of tumour marker (alpha-fetoprotein) response in advanced
      hepatocellular carcinoma patients with thalidomide treatment. PATIENTS AND
      METHODS: Forty-two advanced hepatocellular carcinoma patients with baseline alpha
      fetoprotein levels above 200 ng/mL and thalidomide therapy were included. Serum
      alpha-fetoprotein levels were measured every 4 weeks. alpha-fetoprotein response
      was defined as a 50% or greater reduction of alpha-fetoprotein levels for 4 or
      more weeks during treatment. Radiographic response was assessed by World Health
      Organization criteria; survivals were estimated by Kaplan-Meier method and
      prognostic factors were assessed by Cox's proportional hazard model. RESULTS:
      With intention-to-treat analysis, radiographic response and alpha-fetoprotein
      response were obtained in 7% (three of 42, 95% confidence interval: 0-15) and 24%
      (10 of 42, 95% CI: 10-38) of patients, respectively. All radiographic response
      was observed in alpha-fetoprotein responders. Multivariate analyses showed alpha
      fetoprotein response was independent prognostic factor for both progression-free
      survival (relative risk = 0.394, 95% CI: 0.189-0.820, P = 0.013) and overall
      survival (relative risk = 0.241, 95% CI: 0.096-0.606, P =0.003), whereas
      radiographic response was not. CONCLUSION: alpha-fetoprotein response can more
      accurately reflect the biological response of advanced hepatocellular carcinoma
      to thalidomide therapy than radiographic response.

PMID- 16091060
TI  - Lamivudine therapy in chronic delta hepatitis: a multicentre randomized
      controlled pilot study.
AB  - BACKGROUND: Delta virus (HDV)-related chronic hepatitis is difficult to treat.
      AIMS: To evaluate the efficacy of lamivudine 100 mg daily on serum HDV-RNA,
      hepatitis D virus antibodies and alanine aminotransferase levels, liver
      histology, and on hepatitis B surface antigen seroconversion. METHODS: Thirty-one
      hepatitis B surface antigen-positive, HDV-RNA-positive patients with ALT > or =
      1.5 upper normal level and compensated liver disease were randomized (1:2 ratio)
      to placebo (group A, n = 11) or lamivudine (group B, n = 20) for 52 weeks;
      thereafter, all patients were given lamivudine for 52 weeks and followed up for
      16 weeks. RESULTS: Twenty-five patients (81%) completed the study. No patient was
      HDV-RNA-negative at week 52; three patients (11%) were negative at week 104. Two
      of them remained HDV-RNA-negative at week 120, and one lost the hepatitis B
      surface antigen without seroconversion. Paired pre-treatment and week 104 liver
      biopsies were available from 19 patients: of which three of seven (43%) from
      group A and two of 12 patients (17%) from group B had a > or =2 point decrease in
      the Ishak necroinflammatory score. CONCLUSION: A sustained complete response was
      achieved in 8% of hepatitis D virus-infected patients treated with lamivudine and
      a partial histological response in 26% of them. Hepatitis D virus viraemia was
      unaffected, even in patients when hepatitis B virus replication was lowered by
      lamivudine therapy.

PMID- 16091061
TI  - Trends in the management and survival of digestive tract cancers among patients
      aged over 80 years.
AB  - BACKGROUND: Advances have occurred in the management of digestive tract cancers,
      but it is not known how much they have benefited the elderly. AIMS: To determine
      trends in treatment, stage at diagnosis and prognosis of digestive tract cancers
      among patients aged > or =80 years in two well-defined French populations.
      DESIGN: Time trends were studied in three age classes and in 5 four-year time
      intervals. A multivariate relative survival analysis was performed to estimate
      the independent effect of both age and period on prognosis. RESULTS: Five-year
      relative survival rates were 1.9% for oesophageal cancer, 12% for stomach cancer,
      41% for colon cancer and 37% for rectal cancer. The survival rates improved
      between the first and the fifth period for all cancer sites except for
      oesophageal cancer. This improvement remained significant after adjustment for
      age, sex, site and treatment. It was associated with an increase in the
      proportion of patients who underwent curative resection. Very few patients
      received adjuvant chemotherapy. The use of adjuvant radiotherapy for rectal and
      oesophageal cancers did not significantly increase over time. CONCLUSIONS: Except
      for oesophageal cancers, substantial advances in the care of digestive tract
      cancers in the elderly have been achieved. Surgery should not be restricted on
      the basis of age alone. Further improvements can be made in particular to enhance
      adjuvant therapy whenever possible.

PMID- 16091062
TI  - Trends in the prevalence of peptic ulcer disease and Helicobacter pylori
      infection in family physician-referred uninvestigated dyspeptic patients in Hong
      Kong.
AB  - BACKGROUND: Peptic ulcer disease is mainly caused by Helicobacter pylori
      infection and the use of non-steroidal anti-inflammatory drugs. AIM: To
      investigate the trends in the prevalence of peptic ulcer disease, H. pylori
      infection and non-steroidal anti-inflammatory drug use in uninvestigated
      dyspeptic patients over recent years in Hong Kong. METHODS: Data from consecutive
      patients with uninvestigated dyspeptic symptoms referred by family physicians for
      open access upper endoscopy during 1997 and 2003 were analysed in relation to
      peptic ulcer disease, H. pylori infection and non-steroidal anti-inflammatory
      drug use. RESULTS: Among 2700 patients included, 405 (15%) had peptic ulcer
      disease and 14 (0.5%) had gastric cancer. There was a reduced trend from 1997 to
      2003 in the prevalence of peptic ulcer disease (17, 20, 14, 16, 13, 14 and 14%,
      respectively, chi2 = 5.80, P = 0.016) (mainly because of decrease in duodenal
      ulcers), H. pylori infection (44, 50, 49, 44, 40, 40, 36 and 43%, respectively,
      chi2 = 13.55, P < 0.001) and non-steroidal anti-inflammatory drug use (13, 5, 5,
      6, 3, 4, 4 and 5% respectively, chi2 = 13.61, P < 0.001). The prevalence of
      peptic ulcer disease, H. pylori infection and non-steroidal anti-inflammatory
      drug use between 2001 and 2003 were significantly lower than that between 1997
      and 2000 (17% vs. 13%, OR = 0.78, 95% CI: 0.63-0.96, P = 0.020 for peptic ulcer
      disease; 47% vs. 39%, OR =0.72, 95% CI: 0.60-0.86, P < 0.001 for H. pylori
      infection; and 6% vs. 4%, OR = 0.56, 95% CI: 0.39-0.82, P = 0.002 for non
      steroidal anti-inflammatory drug use). H. pylori infection was associated with
      both duodenal ulcer (OR = 15.87, 95% CI: 10.60-23.76, P < 0.001) and gastric
      ulcer (OR = 3.12, 95% CI: 2.15-4.53, P < 0.001) whereas non-steroidal anti
      inflammatory drug use was only associated with gastric ulcer (OR = 2.97, 95% CI:
      1.70-5.20, P < 0.001). CONCLUSIONS: The prevalence of peptic ulcer disease,
      mainly duodenal ulcers, was reduced in association with a decreasing trend in the
      prevalence of H. pylori infection and non-steroidal anti-inflammatory drug use
      from 1997 to 2003.

PMID- 16091063
TI  - Dyspepsia consulters and patterns of management: a population-based study.
AB  - BACKGROUND: Although dyspepsia is common, management patterns in the United
      States are unknown. AIM: To determine the pattern of dyspepsia evaluation and
      treatment over 20 years in a population-based cohort, and test the hypothesis
      that the management was influenced by dyspepsia subgroup and gender. METHODS: The
      validated Bowel Disease Questionnaire was mailed to a random sample of Olmsted
      County, Minnesota residents (1988-1990). Of the 835 survey respondents, 213
      subjects were identified as having dyspepsia according to Rome I Criteria. The
      medical chart of each dyspeptic subject who had not denied research authorization
      (n = 206) was reviewed to identify all episodes of care for dyspepsia symptoms 10
      years before and 10 years after the date the Bowel Disease Questionnaire was
      completed. Of these 206 subjects (mean age 47 years, 48% female), 34% had ulcer
      like dyspepsia, 32% had dysmotility-like dyspepsia, and 37% had reflux-like
      dyspepsia. RESULTS: Nearly half (n = 98, 48%) had episodes of care for dyspepsia
      symptoms over 20 years. Of these 98 subjects, 49% had upper gastrointestinal
      endoscopy, 4% motility studies and 12% were tested for Helicobacter pylori. At
      the first visit of the episode of care closest to Bowel Disease Questionnaire
      completion, 72% were seen in primary care, 16% in emergency medicine and 2% in
      gastroenterology. In addition, 13% were referred to gastroenterology clinic
      within this episode. During the study period, 70% were given an 'acid' diagnosis,
      7% a 'motility' diagnosis and 54% a 'functional' diagnosis; 78% received acid
      suppression agents (28% proton pump inhibitors), 18% psychotropic agents and 7%
      prokinetic agents. No significant association was found between gender and test
      usage, specialty referral or type of treatment, although women were three times
      less likely to receive proton pump inhibitors (odds ratio 3.3, 95% CI: 1.2-9.1).
      Symptom severity, frequency and pattern were risk factors for health care seeking
      in dyspepsia. CONCLUSIONS: Delivery of care for dyspepsia was similar among
      dyspepsia subgroups and in men and women.

PMID- 16091064
TI  - Lower oesophageal sphincter pressure and timed barium oesophagogram: two
      objective parameters in the non-invasive assessment of primary achalasia.
AB  - BACKGROUND: The non-invasive assessment of primary achalasia is not precise. AIM:
      To compare investigations before and 1 month after balloon dilation in achalasia.
      METHODS: Fifty-two patients with primary achalasia were enrolled. Subjective and
      objective variables of oesophageal functions were analysed before and 1 month
      after balloon dilation. RESULTS: The mean predilation symptom score, lower
      oesophageal sphincter pressure, height and volume of barium at 5 min were 7.7 +/-
      2.6, 62.0 +/- 25.1 mmHg, 9.2 +/- 6.1 cm and 53.2 +/- 49.8 mL respectively; the
      mean postdilation values were 3.0 +/- 3.0, 34.1 +/- 12.5 mmHg, 7.9 +/- 5.1 cm and
      28.0 +/- 30.1 mL respectively. The before dilation volume of barium at 5 min
      correlates significantly with lower oesophageal sphincter pressure (P < 0.01).
      The mean symptom scores, lower oesophageal sphincter pressure and volume of
      barium at 5 min dropped significantly after intervention (P < 0.01), but the
      reduction in barium height at 5 min was not significant. The percentage changes
      in volume at 5 min significantly predicted the percentage changes in lower
      oesophageal sphincter pressure (P < 0.01). CONCLUSIONS: The volume of barium
      retention at 5 min can predict the lower oesophageal sphincter pressure before
      and after balloon dilation in primary achalasia. This could be used as a non
      invasive objective tool for initial and post-dilation assessment.

PMID- 16091065
TI  - Relationship between diabetes mellitus and adenocarcinoma of the oesophagus and
      gastric cardia.
AB  - BACKGROUND: Obesity is a risk factor for adenocarcinomas of the oesophagus and
      gastric cardia. Diabetes mellitus might mediate that association. AIM: To
      estimate the risk of diabetes mellitus on the development of adenocarcinoma of
      distal oesophagus and gastric cardia beyond that of gastro-oesophageal reflux
      disease. METHODS: A case-control study was performed using a national
      administrative database of the Veterans Administration. RESULTS: A total of 311
      cases of cancer and 10,154 controls were identified. Gender, age, and race were
      risks for cancer. Diabetes was diagnosed in 36% of cases, and 32% of controls (P
      = 0.15). Diabetic complications were diagnosed in 14% of cases and 13% of
      controls (P = 0.60). Multiple logistic regression confirmed the absence of an
      association between cancer and diabetes (odds ratio 1.1, 95% confidence interval
      0.8-1.5) or diabetic complications (odds ratio 0.8, 95% confidence interval 0.6
      1.3), adjusting for age, gender, and race. CONCLUSIONS: Within the limitations of
      this case-control study, there is no evidence of an association between diabetes
      and adenocarcinoma of the oesophagus or gastric cardia among US veterans with
      gastro-oesophageal reflux disease.

PMID- 16091066
TI  - Helicobacter pylori eradication, CYP2C19 and omeprazole doses.

PMID- 16091067
TI  - The efficacy of Helicobacter pylori eradication related to CYP2C19 metabolism.

PMID- 16091070
TI  - The relationship between autonomic nervous activity and physical activity in
      children.
AB  - BACKGROUND: There have been few studies that have reported on heart rate
      variability and the development of autonomic nervous function in children. This
      study investigated the relationship between heart rate variabilities at night and
      physical activity in children. METHODS: The study subjects were 29 children,
      including 17 boys and 12 girls. The daily activity product and heart rate
      variabilities during sleep at night (00.00-05.00 hours) were measured and several
      aspects of these parameters were analyzed. In one child (an 8-year-old girl),
      heart rate variability and the physical activity product were measured for 12
      days. RESULTS: There was a negative correlation between the mean R-R interval and
      the duration (min) of heavy exercise per day (r = -0.39, P < 0.05). In the 8-year
      old girl, from whom data was obtained for 12 days, the duration of heavy exercise
      per day was negatively correlated with the mean R-R interval (r = -0.63, P <
      0.05), the number of changes in successive R-R intervals greater than 50 msec
      (RR50) (r = -0.74, P < 0.01), and the high frequency (HF) component (r = -0.66, P
      < 0.05). Furthermore, the daily number of steps was negatively correlated with
      the mean R-R interval (r = -0.66, P < 0.05), RR50 (r = -0.71, P < 0.05) and the
      HF component (r = -0.66, P < 0.05). There was a negative correlation between the
      amounts of energy consumption and the mean R-R interval (r = -0.69, P < 0.05).
      There was a negative correlation between the amounts of energy consumption and
      RR50 (r = -0.76, P < 0.01). Moreover, there was also a negative correlation
      between the amount of energy consumption and the HF component (r = -0.71, P <
      0.05). CONCLUSION: These findings suggested that physical activities increase
      heart rate during sleep, but reduce parasympathetic nervous activity at night.
      Because both the HF component and RR50 reduce with growth, the exercise-related
      inhibition of parasympathetic nervous activity may be a developmental stimulus to
      reach a balanced autonomic nervous pattern in adults.

PMID- 16091071
TI  - Lamivudine treatment in maternally transmitted chronic hepatitis B virus
      infection patients.
AB  - BACKGROUND: Lamivudine treatment in chronic carriers who acquired hepatitis B
      virus through maternal transmission were investigated. METHODS: A total of 29
      subjects (Male:Female, 24:5; mean age, 14.7 +/- 5.6 years) who were hepatitis B e
      antigen (HBeAg) seropositive for >6 months, alanine aminotransferase (ALT) was
      >1.3 times of upper limit of normal value, and receiving a 52 week-long
      treatment, received open-label lamivudine (3 mg/kg per day, maximum 100 mg/day).
      Another 29 subjects matched for gender, age, liver function, and HBeAg status
      followed up before the introduction of lamivudine served as the control group.
      The control group did not receive any treatment and were evaluated at week 52
      after the onset of abnormal ALT. Mothers of all study subjects were hepatitis B
      surface antigen (HBsAg) carriers. A successful treatment response at week 52 was
      defined as: (i) undetectable hepatitis B virus DNA by real time polymerase chain
      reaction; (ii) normal ALT; and (iii) HBeAg/anti-HBe seroconversion. Lamivudine
      resistant YMDD mutants were checked at week 52. RESULTS: The lamivudine group did
      not reach a better successful treatment response rate than the control group (17
      vs 10%, P = 0.44), except in patients with a baseline ALT >5 times of the upper
      limit of normal value. YMDD mutants developed in 34% of patients in the
      lamivudine group. CONCLUSION: Lamivudine treatment is effective for maternally
      transmitted subjects with high ALT.

PMID- 16091072
TI  - Is leptin a predictive factor in the end of therapy response in chronic hepatitis
      B?
AB  - BACKGROUND: The purpose of this study was to determine the leptin levels in
      children with chronic hepatitis B virus (HBV) infection, and to evaluate the
      effect of serum leptin levels on the end of therapy response (ETR). It is known
      that leptin stimulates T-cell immunity and so T-cell mediated immune response is
      critical in the outcome of chronic HBV infection. METHODS: Leptin levels in
      children with chronic HBV infection were investigated and its effects on the ETR
      in 24 children who were treated with interferon-alpha and lamivudine combination
      therapy were evaluated. RESULTS: The mean leptin level of the patients was higher
      than that of healthy children (P = 0.034). Of the patients, seven (29.2%) had
      ETR. The mean hepatic activity index and portal inflammation score were higher,
      the HBV DNA was lower, and the leptin level was similar in children with ETR when
      compared to others (P = 0.017, P = 0.04, P = 0.007, P = 0.34, respectively). HBV
      DNA and the fibrosis score were positively correlated (P = 0.016). CONCLUSION:
      Although the higher leptin value observed in children with ETR was not
      statistically significant, because of close interactions between leptin,
      cytokines and lymphocytes, it is thought that leptin should be investigated as a
      predictive factor of ETR in further studies.

PMID- 16091073
TI  - Epidemiologic picture of Kawasaki disease in Korea, 2000-2002.
AB  - BACKGROUND: The aim of this study was to investigate the incidence rate and
      epidemiologic patterns of Kawasaki disease in Korea for a 3 year period during
      2000 to 2002. METHODS: An epidemiologic survey on Kawasaki disease was
      retrospectively performed. The questionnaire was sent to all 112 hospitals having
      pediatric residency programs, and obtained data were analyzed. RESULTS: The 9150
      cases of Kawasaki disease from 92 hospitals which responded (response rate,
      82.1%) included 5515 males and 3635 females (male : female ratio, 1.52:1). The
      incidence rate per 100,000 children <5 years old was 73.7 in 2000, and increased
      to 90.8 in 2001, and 95.5 in 2002 (average rate, 86.4). The monthly number of
      patients was slightly higher in May, June and July. Their mean age of onset, the
      proportion of sibling cases, and a rate of recurrent cases were 30.5 months,
      0.17%, and 2.9%, respectively. Coronary arterial abnormalities occurred in 18.6%
      of cases including dilatations of 17.3% and aneurysms of 3.1%. CONCLUSION: The
      average annual incidence, 86.4/100 000 in children <5 years old is the second
      highest rate in the world.

PMID- 16091074
TI  - The use of pethidine as pre-medication to prevent anoxic spells in patients with
      tetralogy of Fallot.
AB  - OBJECTIVE: The aim of this study was to determine whether morphine-HCl or
      pethidine-HCl differ as pre-medication to prevent anoxic spell in patients with
      tetralogy of Fallot (TOF) at catheterization. METHODS: A 3 year retrospective
      case notes review study of 46 consecutive patients who underwent cardiac
      catheterization from 1998 to 2001 was conducted. In a prospective 1 year
      randomized control study, 10 patients diagnosed as TOF and admitted to Tokyo
      Women's Medical University, The Heart Institute of Japan, Tokyo, in 2002 were
      randomized to receive morphine or pethidine as pre-medication for cardiac
      catheterization. The incidence of anoxic spell before and after cardiac
      catheterization was investigated in both studies. RESULTS: In the case notes
      review, a total of 10 out of the 46 patients showed anoxic spell study: eight out
      of 24 patients in the morphine group and two out of 22 in the pethidine group.
      The difference in the incidence was statistically significant (P < 0.05, Fisher's
      exact test). Four patients in the prospective study showed anoxic spell: three
      out of six in the morphine group and one out of four in the pethidine group (odds
      ratio = 3.0). Overall, 14 out of 56 patients had anoxic spell: 11 out of 30 in
      the morphine group and three out of 26 in the pethidine group (P = 0.03).
      CONCLUSION: The incidence of hypoxic spells in patients with TOF undergoing
      cardiac catheterization is reduced by the use of pethidine-HCl as pre-medication
      compared to morphine. This has important clinical implications.

PMID- 16091075
TI  - A 28-year trend of infective endocarditis associated with congenital heart
      diseases: a single institute experience.
AB  - BACKGROUND: Infective endocarditis (IE) is still one of the major complications
      of congenital heart disease and, therefore, prevention has always been an
      important issue. But there has been no large scale investigation of IE in Japan.
      METHODS: Clinical and microbiological features in 183 patients with congenital
      heart diseases complicated with infective endocarditis (IE), which were treated
      in our institute in the last 28 years, were reviewed. RESULT: During the period,
      the age distribution of the patients shifted to an older age; 80% were older than
      15 years in the latest 7 year period. In the underlying diseases more complex
      conditions increased, such as the post Rastelli operation. Dental or oral
      diseases were the major preceding events and Streptococcus was the major pathogen
      throughout the study periods in the data. CONCLUSION: The result indicates the
      importance of continuing education for the prevention of IE and oral hygiene
      especially in adult patients with a risk for IE.

PMID- 16091076
TI  - Safety and efficacy of palivizumab prophylaxis in children with congenital heart
      disease.
AB  - BACKGROUND: Infants with congenital heart diseases (CHD) are at high risk for
      Respiratory syncytial virus (RSV) infection, which causes severe respiratory
      distress. Palivizumab, an anti-RSV monoclonal antibody, was licensed in the USA,
      Europe and Canada, and a large-scale placebo-controlled double-blind test in
      these countries confirmed its efficacy and safety. A survey using questionnaires
      to assess usage, prophylactic efficacy, and safety of palivizumab in Japanese
      infants and young children with CHD was conducted. METHODS: The survey was
      conducted between October 2002 and March 2003. The questionnaire asked for
      patients' characteristics, presence of CHD, underlying diseases, starting date
      and number of injection, adverse events, correlation between adverse events and
      treatment with palivizumab, and evaluation of efficacy. RESULTS: In total, 108
      infants were reported from 61 institutions. A total of 60 of the 108 infants
      evaluated without major non-cardiac complications received intramuscular
      injection of 15 mg/kg per month of palivizumab in a manner not consistent with
      approved indications for this drug. A total of 43 cases (39.8%) had complexed
      CHD, while 64 cases (59.3%) had the first injection in October or November. The
      average number of injections was 3.0 +/- 1.4. Seven children (6.5%) had notable
      respiratory infections confirmed by positive test for RSV antigen, and five
      (4.6%) were hospitalized. No children died nor received mechanical ventilation.
      The number of adverse events was nine in five cases. There was no significant
      relationship between adverse events and treatment with palivizumab. CONCLUSION:
      Palivizumab is well-tolerated, fairly effective and safe in preventing severe RSV
      infection in infants and young children with CHD.

PMID- 16091077
TI  - Treatment of intestinal perforation in extremely low-birthweight infants.
AB  - BACKGROUND: The mortality of intestinal perforation in extremely low-birthweight
      infants (ELBWI) is high. It still remains to be determined whether peritoneal
      drainage is a definitive treatment instead of laparotomy. The authors used
      bedside peritoneal drainage (BSPD) as the diagnostic procedure, and exchange
      transfusion (ET) as the preparatory procedure for invasive stress of laparotomy.
      The treatment protocol is composed primarily of laparotomy combined with BSPD and
      ET. METHODS: ELBWI who developed intestinal perforation during hospitalization
      between 1993 and 2000 were treated according to the aforementioned protocol.
      Their medical records were examined retrospectively. RESULTS: Eight ELBWI were
      identified. The subjects' birthweights ranged from 553 to 892 g and the
      gestational age ranged from 23 to 26 weeks. The subjects consisted of five cases
      with idiopathic intestinal perforation, two cases with necrotizing enterocolitis,
      and one case with meconium plug syndrome. Laparotomy was performed in all cases,
      and BSPD was performed in seven cases. Intestinal perforation was definitively
      diagnosed by X-ray only in three cases, while by stool-like drainage in BSPD in
      the other five cases. Seven (87.5%) cases survived. CONCLUSION: In this limited
      experience, the treatment mainly composed of laparotomy combined with BSPD and ET
      appeared beneficial.

PMID- 16091078
TI  - Serum malondialdehyde level in children infected with Vampirolepis nana.
AB  - BACKGROUND: Vampirolepis nana is the only human tapeworm in which the
      intermediate host is not necessary and transmission is from person to person. In
      this study the changes of serum malondialdehyde level, that is, the oxidative
      stress hypothesis in patients infected with V. nana, was investigated. METHODS:
      Serum malondialdehyde concentration activity was measured in 32 patients who were
      positive for intestinal parasite of V. nana. Levels were obtained for the
      positively infected patients and their age and gender were matched to 32 healthy
      controls. RESULTS: The difference between malondialdehyde levels of patients
      infected with V. nana and the control group was statistically significant both
      for females (P < 0.05) and males (P < 0.05). In the patient and control groups,
      no correlation was found between age and malondialdehyde levels both in females
      and males. In addition, no significant correlation could be found between
      malondialdehyde levels of both females and males for the patient and control
      groups. CONCLUSION: Malondialdehyde levels were clearly increased in the patients
      infected with V. nana.

PMID- 16091079
TI  - The clinical features of respiratory syncytial virus: lower respiratory tract
      infection after upper respiratory tract infection due to influenza virus.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) and influenza virus are the primary
      pathogens of respiratory tract infection. However, epidemics of influenza virus
      infection have been observed to interrupt RSV epidemics (termed an
      epidemiological interference effect). METHODS: At a clinic in Tsuna county, Hyogo
      prefecture, Japan, a total of 1262 outpatients under 6 years of age with lower
      respiratory tract infection due to RSV (RSV-LRTI) and upper respiratory tract
      infection due to influenza virus (FLU-URTI) in three successive winter seasons
      (1999-2000, 2000-2001 and 2001-2002) were analyzed. RESULTS: The RSV-LRTI
      epidemic and FLU-URTI epidemic overlapped in each season, but the RSV-LRTI
      epidemic peak preceded that of the FLU-URTI epidemic. Epidemiological
      interference between RSV and influenza virus was observed in the second and third
      season; the number of patients with RSV-LRTI began to decrease after the start of
      the FLU-URTI epidemic and recovered to some extent after the FLU-URTI epidemic
      passed its peak. There were no differences in onset age, male-to-female ratio and
      severity of RSV-LRTI in outpatients before and after the start of the FLU-URTI
      epidemic in all the three seasons. CONCLUSION: An epidemiological interference
      between RSV and influenza virus was observed in Tsuna county in two of the three
      winter seasons. However, there was no difference between the clinical features of
      the patients with RSV-LRTI before and after the start of the influenza virus
      infection epidemic. The data suggest that the clinical severity of RSV infection
      is not changed by the epidemiological interference effect of influenza virus
      infection epidemics.

PMID- 16091080
TI  - Risk factors for the different types of chronic lung diseases of prematurity
      according to the preceding respiratory distress syndrome.
AB  - BACKGROUND: Recently, atypical chronic lung disease (CLD) of prematurity that
      develops in the absence of preceding respiratory distress syndrome (RDS) have
      been observed frequently. The specific risk factors for atypical CLD that are
      presumed to be different from those for classical CLD that develops following RDS
      were assessed. METHODS: Prospective cohort analysis was done from 115 very low
      birthweight infants who were born in Seoul National University Hospital, Seoul,
      Korea, and survived more than 36 weeks postmenstrual age or 28 days of life. All
      subjects were classified into either a preceding RDS group (n = 35) or a non-RDS
      group (n = 80). Logistic regression analysis was done for the multivariate
      assessment of specific risk factors for CLD in both groups. RESULTS: The analysis
      showed that short gestational age (GA; relative risk [RR], 3.1 per 1 week
      decrement; 95% confidence intervals [CI], 2.7-3.4), of the male gender (RR, 9.8;
      CI, 0.9-112), and poor response to surfactant (RR, 14; CI, 1.2-156) were
      significant risk factors for CLD in the preceding RDS group. In the non-RDS
      group, chorioamnionitis was one of the significant risk factors for CLD (RR, 4.8;
      CI, 1.1-21) along with short GA and high mean airway pressure (MAP) during the
      first 3 days of life. CONCLUSION: Chorioamnionitis was a risk factor for atypical
      CLD in addition to short GA and high MAP during the early postnatal period, and
      poor response to surfactant was a risk factor for classical CLD in addition to
      short GA and being male. Therefore, CLD is considered to have type-specific risk
      factors.

PMID- 16091081
TI  - Relationship of serum interleukin-7 concentration and the coagulation state in
      children with nephrotic syndrome.
AB  - BACKGROUND: Enhanced platelet reactivity may play a significant role in the
      hypercoagulable state of nephrotic syndrome (NS). Thrombocytosis with platelet
      aggregation cause the release of some cytokines, among them interleukin-7 (IL-7).
      The aim of the study was to evaluate serum IL-7 levels in children with the
      symptoms of NS and to determine a correlation between its concentration and
      platelet count, other hemostatic factors, and NS intensity. METHODS: The study
      was performed in two groups. I--the examined group of 26 children with NS (12
      boys, 14 girls) aged 6.8 +/- 2.1 years, subjected to two examinations: A--before
      treatment, B--during treatment with prednisone (60 mg/kg 24 h after albuminuria
      regression); and II--the control group (C) of 20 healthy children. Serum IL-7
      level was assayed by enzyme-linked immunosorbent assay method using a R & D
      Quantikine set. RESULTS: In group I, IL-7 level in examination A (33.33 +/- 33.24
      pg/mL) was higher than in the control subjects (P < 0.01). In examination B, IL-7
      concentration was reduced to the level of 10.86 +/- 5.22 pg/mL and did not differ
      from the controls (P > 0.05). A positive correlation was observed between IL-7
      and platelet count and serum fibrinogen level. A negative correlation was noted
      with antithrombin III concentration. No correlation was found with serum levels
      of albumin and cholesterol or urine protein. CONCLUSION: In children with NS,
      serum IL-7 level increases proportionally to the elevated platelet count and
      other hemostatic components, but shows no correlation with serum albumin or urine
      protein.

PMID- 16091082
TI  - Usefulness of the addition of metformin to insulin in pediatric patients with
      type 1 diabetes mellitus.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of metformin in
      addition to insulin therapy in adolescents and young adults with type 1 diabetes
      mellitus. METHODS: Nine patients, two males and seven females, aged 18.1 +/- 3.0
      years, with type 1 diabetes mellitus were studied. They were relatively
      overweight with a body mass index (BMI) of 24.2 +/- 1.8 and had high levels of
      HbA1c at 9.5 +/- 1.2% despite high doses of insulin of 74.0 +/- 31.2 U/day.
      Metformin at the dose of 500-750 mg daily was administered to the patients in
      addition to insulin therapy for 1 year. RESULTS: HbA1c, BMI and insulin dose were
      compared before 1 year without metformin therapy, at baseline, and at 3, 6 and 12
      months during the use of metformin in addition to insulin therapy. HbA1c lowered
      (8.6 +/- 1.4**, 8.4 +/- 1.3**, 8.4 +/- 1.2*%), BMI was reduced (23.9 +/- 1.7*,
      23.8 +/- 1.8, 23.5 +/- 1.8*), and insulin requirement decreased (69.8 +/- 29.7*,
      68.7 +/- 29.8**, 67.3 +/- 29.1**U/d) significantly after the start of metformin
      therapy (*P < 0.05, **P < 0.01 vs at baseline). There were no adverse events, not
      even lactic acidosis, during the study period. CONCLUSION: Metformin is safe and
      may represent a useful adjunct to the management of type 1 diabetes mellitus in
      adolescents and young adults who have poor glycemic control despite a large
      amount of insulin.

PMID- 16091083
TI  - The protective role of melatonin in experimental hypoxic brain damage.
AB  - BACKGROUND: It is known that oxygen-derived free radicals play an important role
      in the pathogenesis of brain injury. Melatonin is a powerful scavenger of the
      oxygen free radicals. In this study, the protective effect of melatonin against
      the damage inflicted by reactive oxygen species during brain hypoxia was
      investigated in newborn rats using biochemical parameters. METHODS: For
      biochemical analyses, the levels of lipid peroxidation product (malondialdehyde
      ([MDA]), levels of reduced glutathione (GSH) and the activities of superoxide
      dismutase (SOD) and catalase (CAT) were estimated. RESULTS: After the third day
      of brain hypoxia, the brain levels of MDA increased. Pretreatment of animals with
      melatonin abolished the rise in MDA induced by hypoxia. GSH concentration did not
      increase by pretreatment with melatonin. Additionally, the activities of two
      antioxidative enzymes (SOD and CAT) decreased after the experimental period with
      melatonin only preventing the change of CAT. The activity of SOD was not
      influenced by melatonin administration as expected. CONCLUSION: In this
      experimental study, exogenously administered melatonin effectively protected
      against brain injury by oxidative stress. This protective effect of melatonin may
      be due to its direct scavenger activity and activation of CAT. Thus, melatonin
      may potentially be useful in the treatment of neurodegenerative conditions that
      may involve free radical production, such as perinatal hypoxia.

PMID- 16091084
TI  - Assessment of the short-term effect of antispastic positioning on spasticity.
AB  - BACKGROUND: This study was performed in order to investigate the effect of
      antispastic positioning on spasticity by using different assessment methods.
      METHODS: A total of 16 patients (11 males [68.75%] and five females [31.25%]),
      diagnosed as spastic diplegic and referred to the School of Physical Therapy and
      Rehabilitation, Paediatric Rehabilitation Unit for treatment, were included in
      this study. The mean age of patients was 6.43 +/- 1.99 years (range, 4-13 years).
      Passive dorsi-flexion movement was measured by using goniometer and intensity of
      spasticity was determined by using Modified Ashworth Scale (MAS) and
      electromyography. For the objective measurement of severity of spasticity,
      Hoffman reflex (H) and Hoffman reflex/motor response (H/M) ratios were used.
      Children were placed in an antispastic position for 20 min. The patient was
      placed in a sitting position, by a physiotherapist, with hips abducted at a 45
      degrees angle and externally rotated, knees extended, and ankles placed in a
      neutral position. RESULTS: The decrease in H responses, H/M ratios, MAS values
      and the increase in goniometric measurement values were found statistically
      significant after antispastic positioning (P < 0.05). CONCLUSION: Our study
      supports that antispastic positioning can be used with neurodevelopmental
      treatment approaches when it is required. Antispastic positioning may help
      exercises to be performed more easily, and also has importance in a home exercise
      program to prevent muscle contractures and joint limitation in children with long
      term spastic diplegia.

PMID- 16091085
TI  - Cross-cultural comparison of the neurobehavioral characteristics of Chinese and
      Japanese neonates.
AB  - BACKGROUND: Similarities and differences in the neurobehavioral repertoire of
      neonates from different cultures have been noted using the Brazelton Neonatal
      Behavioral Assessment Scale (NBAS). By identifying the behavioral attributes of
      newborns that are seen more universally versus those that are culture-specific,
      comparative studies increase understanding of the roles of cultural factors in
      shaping the behavioral trajectory of infants. This study compared the
      neurobehavioral characteristics of neonates in Chengdu, China and Nagasaki,
      Japan. METHODS: The Brazelton NBAS was administered within the first week of life
      to 40 Chinese and 62 Japanese healthy, full-term neonates in Chengdu and
      Nagasaki. RESULTS: The two groups differed significantly in birthweight, gender,
      age at time of exam, mode of delivery, and gestational age. When these variables,
      in addition to group status (Chinese or Japanese), were entered into multiple
      linear analyses with NBAS cluster scores as dependent variables, group status
      independently predicted Range of State and Habituation scores. The group status
      did not predict Orientation, Motor, Regulation of States, Autonomic Stability,
      and Abnormal Reflexes cluster scores. CONCLUSION: These results suggest that
      Japanese newborns habituated more readily to stimuli, and were less irritable
      than newborns in the Chinese sample. The infants in the two groups shared many
      similar neurobehavioral characteristics as well. The implications of these
      similarities and differences were discussed.

PMID- 16091086
TI  - Luteinizing hormone-releasing hormone analog treatment for a criminal sexual
      habit caused by male precocious puberty.

PMID- 16091087
TI  - Oseltamivir phosphate in infants under 1 year of age with influenza infection.

PMID- 16091088
TI  - Evidence-based practice: Where next? What, now?

PMID- 16091089
TI  - First footsteps in tsunamiland.

PMID- 16091090
TI  - Emergency departments under siege?

PMID- 16091091
TI  - HIV/AIDS in Papua New Guinea: an unfolding disaster?

PMID- 16091092
TI  - Evidence-based medicine: arguments for and against.
AB  - In this article I will discuss the various definitions of evidence-based medicine
      (EBM), and summarize the application, criticisms and limitations of EBM. The
      spectrum of evidence, from pathophysiological inference to randomized controlled
      trials, will be presented as a mechanism for filtering bias with more rigorous
      evidence being required when bias is more likely. Although randomized controlled
      trials and meta-analyses are at the top of the evidence hierarchy, they are not
      always necessary, might not be the most appropriate forms of evidence for some
      clinical questions, and have their own limitation that need to be understood.
      Best available evidence, applied to individual patients, is the corner stone of
      EBM. Although there are valid criticisms and limitations of EBM, if these are
      understood then the practice of EBM can provide guidance to the clinician and
      enhance patient care.

PMID- 16091093
TI  - History of evidence-based medicine. Oranges, chloride of lime and leeches:
      barriers to teaching old dogs new tricks.
AB  - Knowledge translation is the process of taking evidence from research and
      applying it in clinical practice. In this article I will cite some pivotal
      moments in the history of medicine to highlight the difficulties and delays
      associated with getting evidence into practice. These historical examples have
      much in common with modern medical trials and quality improvement processes. I
      will also review the reasons why evidence is not used and consider what factors
      facilitate the uptake of evidence. Understanding these concepts will make it
      easier for individual clinicians and institutions to change clinical behaviour
      and provide a starting point for those looking at implementing 'new' practices,
      new therapies and clinical guidelines. Finally, I will offer a list of criteria
      that clinicians might choose to consider when deciding on whether or not to adopt
      a new practice, treatment or concept.

PMID- 16091094
TI  - Likelihood ratios increase diagnostic certainty in pulmonary embolism.
AB  - Pulmonary embolism (PE) is a difficult diagnosis to confirm. The choice of tests
      has led to a myriad of algorithms. Diagnostic uncertainty can be quantified by
      the application of the tests' likelihood ratios (LR). Positive and negative LR
      enable the conversion of a pretest to a post-test probability, given a positive
      and negative test result, respectively. Thus, a pretest probability of <17% and a
      negative D-dimer with a negative LR of 0.05 (sensitivity 98%, specificity 40%)
      lead to a post-test probability of PE of <1%. Ventilation perfusion (V/Q) scans
      with a normal, very low, low, intermediate and high probability result have an LR
      of 0, 0.125, 0.25, 1 and 17, respectively. Also, patients with a V/Q scan result
      other than normal or high probability still have a post-test probability of PE
      from 3 to 65%. Positive and negative computed tomography pulmonary angiograms
      (CTPA) have an LR of 8.6 and 0.06, respectively (sensitivity 95%, specificity
      89%). Patients with a high pretest probability and negative CTPA again still have
      a post-test probability of more than 10%. However, as the post-test probability
      after one test becomes the pretest probability for the next, test results used
      cumulatively progressively narrow the gap to a final diagnosis. The post-test
      probability after a D-dimer, V/Q scan, CTPA, leg ultrasound or pulmonary
      angiography, alone or in any combination or in any order, can be calculated using
      their LR. Use of LR thus assists in the precise interpretation of test results,
      such as in complex algorithms for PE.

PMID- 16091095
TI  - Evidence-based emergency medicine at the 'coal face'.
AB  - While evidence-based medicine may be trumpeted by zealots, managers and
      politicians, incorporating it into clinical practice is easier said than done.
      The present article aims to show that it can be achieved and gives some clinical
      examples to illustrate this. An appendix contains a summary of useful databases
      and websites for accessing good medical information and evidence, quickly and
      reliably near the bedside.

PMID- 16091096
TI  - Rapid health assessment in Aceh Jaya District, Indonesia, following the December
      26 tsunami.
AB  - OBJECTIVES: To rapidly determine the public health impact of the Asian tsunami on
      the population of three communities in Aceh Jaya District, Indonesia, and to
      prioritize health interventions. METHODS: Rapid health assessment, utilizing
      direct observations, interviews with key informants, a single focus group
      discussion, town mapping, a review of medical records and a systematic random
      sample of the entire town of Calang, capital of Aceh Jaya District, Indonesia.
      RESULTS: Almost 100% of dwellings were destroyed in all three communities. For
      the town of Calang: only 18.2% of the pre-tsunami population remained 2 weeks
      following the disaster, with an estimated 70% of the population having died at
      the time of impact; government estimates of the remaining population were
      inflated by approximately 250%; mortality rates were not elevated post-tsunami;
      100% of the population lacked access to sanitation and clean water; 85% of
      children under 5 years reported diarrhoea over the preceding 2 week period; 95%
      of individuals with a medical complaint reported satisfactory access to clinical
      care; acute malnutrition was not a significant problem; and over one-fifth of
      households were hosting an orphan. For the villages of Rigah and Sayeung:
      approximately 46.2 and 86.0% of the population survived the tsunami impact,
      respectively; mortality rates were not elevated post tsunami; 100% of the
      population lacked access to sanitation and clean water; diarrhoea was the main
      cause of morbidity; primary care services were available only in Rigah; and only
      Rigah had received external assistance. CONCLUSIONS: Almost two-thirds of the
      population of the three communities died as a result of the tsunami's impact.
      Although mortality rates were not elevated post tsunami, significant threats to
      public health persisted, especially water-borne diseases. Priority activities
      included emergent environmental health interventions, mobile clinics to the two
      villages and a more detailed assessment of the needs of orphans. Data were shared
      with agencies better placed to address needs in the areas of shelter and food
      aid.

PMID- 16091097
TI  - Epidemiology of unarmed threats in the emergency department.
AB  - OBJECTIVE: To evaluate the precipitants, subject characteristics, nature and
      outcomes of unarmed threats in the ED. METHODS: A 12 month prospective survey of
      security codes precipitated by an unarmed threat (Code Grey). RESULTS: Data were
      collected on 151 subjects. The Code Grey rate was 3.2/1000 ED presentations. They
      were most frequent on Saturday and in the late evening/early morning. There were
      verbal or physical threats of violence made to staff on 104 occasions (69%, 95%
      confidence interval [CI] 61-76) and a perceived threat of patient self-harm on
      114 occasions (76%, 95% CI 68-82). Median time to be seen by a doctor was 8 min
      (interquartile range [IQR]: 2-21 min) and median time from presentation to Code
      was 59 min (IQR: 5-222 min). Sixteen subjects (11%, 95% CI 6-17) had a history of
      violence, 45 (30%, 95% CI 23-38) were affected by alcohol, 25 (17%, 95% CI 11-24)
      had used illicit drugs and 79 (52%, 95% CI 44-60) had a significant mental
      illness contributing to the Code Grey. Seventy-one patients (47%, 95% CI 39-55)
      required psychiatric admission, 49 (79%, 95% CI 66-88) involuntarily. CONCLUSION:
      Acutely agitated subjects pose a threat to themselves and the staff caring for
      them. The reason for the agitation is multifactorial and the majority arrive in a
      behaviourally disturbed state requiring early intervention. The times most likely
      to result in a Code Grey coincide with least available resources: ED and hospital
      risk management policies must account for this. A coherent approach by ED to this
      population is required to optimize patient and staff outcomes.

PMID- 16091098
TI  - HIV antibody seroprevalence in the emergency department at Port Moresby General
      Hospital, Papua New Guinea.
AB  - OBJECTIVE: To determine the prevalence of HIV antibody in patients presenting to
      the ED at Port Moresby General Hospital in Papua New Guinea. METHOD: Three
      hundred patients in whom blood samples were taken for investigation of illness or
      injury between April and July 2003 were surveyed for HIV antibodies. Sex, age and
      presenting illness were recorded. RESULTS: Fifty-four tests (18%, 95% confidence
      interval [CI] 14-23%) were positive. Forty-seven per cent were men and 53% were
      women. The most common presenting illnesses were respiratory tract infections
      (37%) and gastrointestinal tract infections (26%). Because of resource
      constraints results were not linked to patients and there was no follow up.
      CONCLUSION: These limited data support the prediction that the developing
      HIV/AIDS epidemic in Papua New Guinea will be serious.

PMID- 16091099
TI  - Substance misuse, anxiety and depression and urgency of presentation to a public
      emergency department in Australia.
AB  - OBJECTIVES: To establish the prevalence and comorbidity of substance-related
      problems and anxiety and depression, among ED presentations, and to compare the
      prevalence of these conditions among more and less urgent presentations. DESIGN
      AND SETTING: Cross-sectional survey of ED presentations over a 14 day period (24
      h/day) at the Gold Coast Hospital Emergency Department in south-east Queensland,
      Australia, in October 2002. MEASURES: Usual level of alcohol consumption (Alcohol
      Use Disorders Identification Test), acute alcohol and illicit drug use (during 24
      h prior to interview), symptoms of anxiety and depression (Hospital Anxiety and
      Depression Scale) and triage category (Australasian Triage Scale). RESULTS:
      Thirty-one per cent of the sample reported usually consuming alcohol at a
      hazardous or harmful level. Twenty per cent of participants reported clinically
      significant levels of anxiety and/or depression, which were in turn significantly
      associated with hazardous and harmful levels of alcohol use. Hazardous/harmful
      alcohol consumption was over-represented among less urgent ED presentations,
      whereas anxiety and depression were more prevalent among more urgent ED
      presentations. CONCLUSIONS: Emergency departments in Australia are appropriate
      settings for the detection of both substance use and mental health problems in
      the wider community. The prevalence of these problems in ED settings is high and
      there is a need for the development of systematic screening and referral
      processes. The evidence of a link between urgency of presentation and these
      problems needs to be further explored.

PMID- 16091100
TI  - Diagnostic use of C-reactive protein in bacteraemic emergency department
      patients.
AB  - OBJECTIVE: To assess C-reactive protein (CRP) as a marker of bacteraemia in ED
      patients. METHODS: A retrospective review of a convenience sample of adult
      patients was conducted at an urban, tertiary care, academic ED. Patients were
      included in the present study if they had CRP and blood cultures taken during
      their ED assessment. Neutropenic patients were excluded. Sensitivity,
      specificity, predictive values and likelihood ratios for CRP in the detection of
      bacteraemia were calculated. RESULTS: Over a 12 month period 1214 patients were
      included in the present study. Blood cultures were positive in 77 (6.3%, 95%
      confidence interval [CI] 5.0-7.6%), and contaminated in 33 (2.7%, 95% CI 1.8
      3.6%). An elevated CRP was 94% sensitive (95% CI 86-98%) and 18% specific (95% CI
      16-20%) for concurrent bacteraemia. The positive likelihood ratio for bacteraemia
      with an elevated CRP was 1.15 (95% CI 1.07-1.23), and the negative likelihood
      ratio was 0.33 (95% CI 0.23-0.49). CONCLUSION: Although the present study has
      limitations, it appears to show that CRP has limited diagnostic utility for the
      detection of bacteraemia in ED patients.

PMID- 16091101
TI  - Assessment of cricoid pressure application by emergency department staff.
AB  - OBJECTIVE: To assess the accuracy of cricoid force applied by ED staff working in
      two hospitals based on the New South Wales central coast. METHODS: A prospective,
      observational study of 38 doctors and 69 nurses working in the ED. Each staff
      member was asked to demonstrate cricoid pressure using a model based on a set of
      weighing scales. Five attempts were measured and a mean value calculated for each
      participant. Subgroup analysis was also performed for specific variables of
      interest. RESULTS: Twenty-seven (25%) participants applied the target cricoid
      force. Of the 80 participants who were outside of the target range, 50 (63%)
      applied less than the target range and 30 (37%) applied more than the target
      range. No statistically significant difference was demonstrated for sex, age,
      qualification or years of experience and the ability to apply cricoid force
      within the target range. More candidates (27) applied the target range than those
      who correctly identified it (12). When methods of instruction were compared there
      was no difference between candidates with one and more than one modality of
      instruction (t-test: t (105) = -0.09, P = 0.9; 95% confidence interval [CI]-0.66
      0.6) and the mean cricoid force applied. Those who had greater than one form of
      instruction applied correct cricoid force at the target range more often than
      those who had received only one form of instruction, this result was significant.
      (chi(2) = 4.24, d.f. = 1, P = 0.04; odds ratio = 2.6; 95% CI 1.03-6.41).
      CONCLUSION: The application of cricoid force by ED staff participating in the
      present study is unreliable, often providing inadequate protection against
      regurgitation. Training using a model integrating the concept of force is
      recommended. The role of cricoid pressure in rapid sequence induction needs to be
      further investigated.

PMID- 16091102
TI  - Triage nurses validly and reliably estimate emergency department patient
      complexity.
AB  - OBJECTIVE: To access the validity and reliability of triage nurse estimates of ED
      patient complexity. METHODS: Prospective, single-blinded evaluation of triage
      nurse estimates of patient complexity, where a high-complexity patient is defined
      as a patient requiring two or more procedures or investigations or consultations.
      Validity of complexity estimates was assessed by comparison with the number of
      actual procedures, investigations and consultations requested. Reliability of
      triage nurse estimates of complexity was assessed by comparison with assessment
      nurse estimates of complexity. RESULTS: The specific proportion of agreement and
      spearman correlation coefficient of triage nurse estimates of complexity with
      actual procedure, investigations and consultation use were 0.83 (95% confidence
      interval [CI] 0.79-0.88) and 0.59 (95% CI 0.51-0.66), respectively. The specific
      proportion of agreement and kappa of triage nurse estimates of complexity with
      assessment nurse estimates were 0.80 (95% CI 0.73-0.87) and 0.59 (95% CI 0.47
      0.71), respectively. CONCLUSIONS: Triage nurses make valid and reliable estimates
      of patient complexity. This information might be used to guide ED work flow and
      ED casemix system analysis.

PMID- 16091103
TI  - Helicopter primary retrieval: tasking who should do it?
AB  - BACKGROUND: Cairns Base Hospital utilizes a helicopter retrieval system, which
      until 2001 had been tasked and staffed by emergency physicians. Since 2001, the
      ambulance service has assumed the role of both tasking and staffing the
      helicopter with intensive care paramedics. The present study examines whether the
      change has resulted in different activation patterns and patient outcomes.
      METHOD: A retrospective chart review over 4 consecutive years, comparing the two
      groups, was carried out examining 30 day mortality, length of in-hospital stay,
      transfer rates, the Revised Trauma Score where appropriate and rates of discharge
      directly from the ED. RESULTS: A total of 374 patients were retrieved (211
      patients in the emergency physician group from 1 April 1999 to 31 March 2001 and
      163 in the ambulance group from 1 April 2001 to 31 March 2003) over the 4 year
      period. The demographics of the two groups were similar. Fifty-four patients in
      the ambulance group (33.1%) were discharged from the ED without admission while
      31 (14.7%) were discharged from the physician group. This was statistically
      significant (P = 0.0001). There were no other significant differences between the
      two groups. The subgroup of patients admitted also did not show any significant
      difference in outcomes. CONCLUSION: The similarities in outcomes for admitted
      patients support the view that both groups have similar tasking criteria for high
      acuity patients and suggest that paramedics are as efficacious as physicians in
      delivering prehospital care in this group of patients. However, for lower-acuity
      patients, there is a statistically significant higher rate of clinically
      unnecessary taskings by the ambulance group. Given the recent fatal aeromedical
      accidents in Queensland (Thursday Island 1998, Rockhampton 1999 and Mackay 2003),
      it would seem prudent to reduce clinically unnecessary retrievals through
      clinical coordination with appropriately qualified emergency physicians.

PMID- 16091104
TI  - Equitable emergency access: rhetoric or reality?
AB  - The present paper is based on an address given at the Australian Financial Review
      Health Congress in February, 2005. Let's start with the underlying premise that
      patients have a valid right to fair and just access to emergency care. Fairness
      and justice are concepts more comfortably placed within legal and sociological
      settings than within health. They refer to our ability to deliver care without
      bias or favour. Our college has published a statement asserting patients' right
      to appropriate access (Patients' Right to Access Emergency Department Care. ACEM
      Policy Statement P31, March 2004). The other underlying premise in this
      discussion is that this issue of equity of access actually matters. It may be of
      significance at a moral level, at a relative resource consumption level, at the
      level of occupation of system capacity, or at the level of clinical outcomes for
      individual patients.

PMID- 16091105
TI  - Thyrotoxic, hypokalaemic periodic paralysis.
AB  - Thyrotoxic, hypokalaemic periodic paralysis is an uncommon, potentially life
      threatening endocrine emergency. Because of the acute onset of neurological
      symptoms patients often initially present to hospital ED. To reduce patient
      morbidity and costs of unnecessary investigations, early recognition and
      appropriate treatment is required. The case of a young man of Singaporean origin
      is presented to highlight current treatment, management and pathophysiology of
      this condition.

PMID- 16091106
TI  - Stroke or encephalitis?
AB  - Viral encephalitis is associated with significant morbidity and mortality,
      particularly when appropriate management is omitted as a result of delayed
      diagnosis. A case of herpes simplex virus type 1 (HSV-1) encephalitis is
      presented, demonstrating that the presentation of confusion, speech difficulties
      and fever with non-specific early brain CT appearances can easily be misdiagnosed
      as pneumonia with stroke. This case highlights the need for increased awareness
      of HSV-1 encephalitis among emergency physicians and radiologists, given that the
      early spectrum of clinical and CT findings can mimic the more common diagnoses of
      sepsis and stroke.

PMID- 16091108
TI  - National Emergency X-radiography Utilization Study: doing what's right for your
      patients.

PMID- 16091109
TI  - Time to turn up the HEAT?

PMID- 16091111
TI  - Chromosomal aberrations in squamous cell carcinomas of the upper aerodigestive
      tract: biologic insights and clinical opportunities.
AB  - Oncogenesis results from a progressive accumulation of genetic aberrations
      consequent to a complex interplay between carcinogenic factors and innate
      infidelity of DNA surveillance mechanisms. Although the development of genetic
      aberrations is random, those conferring survival advantages are selected for in a
      Darwinian manner, thus allowing continuous adaptation to selection pressures.
      Chromosomal aberrations are a prominent manifestation of genetic damage, which
      can be closely linked with tumor behavior and outcome as exemplified by curative
      treatment of chronic myelogenous leukemia resulting from targeting the BCR-ABL
      translocation. In the case of head and neck squamous cell carcinomas (HNSCC),
      chromosomal changes are detectable at all stages of tumor development, providing
      excellent opportunities for genomic prognostication and therapy. Several studies
      have shown that the overall genomic profile of HNSCC is highly consistent, but
      individual tumors vary significantly in their complement of genetic alterations,
      thereby confounding clinical correlation. The application of modern genetic and
      bioinformatic analytic approaches has facilitated the identification of critical
      genomic changes in HNSCC, many of which have been linked to clinical outcome.
      These genetic aberrations represent excellent targets for novel therapeutics, but
      require validation. The initiation of phase III trials evaluating the therapeutic
      utility of genetic aberrations suggests a promising future for genome-based
      treatment of HNSCC.

PMID- 16091112
TI  - Oral precancerous disorders associated with areca quid chewing, smoking, and
      alcohol drinking in southern Taiwan.
AB  - OBJECTIVE: To investigate the prevalence and the associated risk factors of oral
      precancerous disorders in southern Taiwan. METHODS: We conducted a cross
      sectional community survey interviewing 1075 adult subjects, 15 years of age and
      over, gathered from randomly selected 591 households, and spanning five villages
      in southern Taiwan. The study protocol included a visual oral soft tissue
      examination and a questionnaire-based interview. The chi-square test was used to
      test the differences in prevalence of oral precancerous lesions and conditions by
      different "life styles" relating to current risk habits of current areca quid
      chewing, smoking, and alcohol drinking. To control for possible confounding, a
      logistic regression model was used to estimate the Odds Ratios (OR) for
      leukoplakia and oral submucous fibrosis (OSF). RESULTS: 136 precancerous lesions
      and conditions were detected among 1075 subjects (12.7%). The analysis of the
      spectrum of oral precancerous disorders detected, leukoplakia (n = 80), OSF (n =
      17) and verrucous lesions (n = 9), demonstrated an association with gender (P <
      0.001). There were statistically significant associations among leukoplakia (P <
      0.01), OSF (P < 0.0001), and verrucous lesions (P < 0.0001) and the life style of
      current areca quid chewing, smoking, and alcohol drinking. The synergistic effect
      of smoking and areca quid chewing habit on leukoplakia and OSF was demonstrated.
      CONCLUSION: This study reinforces the association of current areca quid chewing
      without tobacco, cigarette smoking, and alcohol drinking to leukoplakia, OSF, and
      verrucous lesions in Taiwan.

PMID- 16091113
TI  - A clinical study of 674 patients with oral lichen planus in China.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease with
      different clinical presentations that can be classified as reticular, atrophic or
      erosive. Although OLP is a relatively common disorder, the reports comprising
      large numbers of OLP patients with specific character are lacking in the
      literature. The purpose of this paper was to describe the clinical
      characteristics of OLP in 674 Chinese patients. METHODS: A total of 674 charts of
      patients with histologically confirmed OLP were collected from Stomatological
      Hospital of Wuhan University between 1963 and 2003. RESULTS: Of the 674 patients,
      65.9% were women and 34.1% were men. The most common clinical presentation was
      the reticular type (51.3%), and symptomatic OLP was noted in 67.5% of the
      patients, mainly in those with the erosive form. The erosive presentations showed
      significantly longer duration, more sites affected and a much greater old
      patients predominance than reticular or atrophic ones. About 90.9% of the
      patients had multiple oral sites of involvement and isolated lower lip lichen
      planus were observed in 60 cases (8.9%) and isolated gingiva lichen in only one
      case (0.2%). Skin involvement of lichen planus was found in 11.4% of patients. No
      statistically significant differences could be identified between OLP and
      diabetes, cardiovascular disease, smoking or alcohol use. Precipitating factors
      that resulted in an exacerbation of the disease were frequently noted and
      included foods, stress, dental cusp and poor oral hygiene. The transformation of
      OLP into malignancy was observed in four patients at sites previously diagnosed
      by clinical examination as erosive or atrophic lichen planus. CONCLUSIONS:
      Patients with OLP in China usually present with distinctive clinical morphology
      and characteristic distribution and few may display lesions with a confusing
      array of forms mimicking other diseases. A long time follow up is of utmost
      importance to detect its malignant transformation.

PMID- 16091114
TI  - Association of GST genotypes with age of onset and lymph node metastasis in oral
      squamous cell carcinoma.
AB  - BACKGROUND: Environment-gene interaction in oral carcinogenesis is well
      demonstrated by phase I and II enzymes that are involved in the metabolism of
      carcinogens. This study investigated the association of glutathione S-transferase
      (GST)T1 and GSTM1 genotypes of phase II enzyme genes with risk for, age of onset,
      and neck lymph node metastasis (LNM) in areca-associated oral squamous cell
      carcinoma (OSCC). METHODS: A total of 114 OSCC male patients and 100 male
      controls were recruited. All subjects were areca users and tobacco smokers. DNA
      was obtained from peripheral blood samples. Genotyping of GSTT1 (non-null/null)
      and GSTM1 (non-null/null) was determined by polymerase chain reaction (PCR)
      analysis using specific primers that only amplify non-null alleles. RESULTS: No
      association was found between GST genotype and the risk of OSCC based on case
      controls. Patients with the GSTT1 null genotype were older at onset (P = 0.03).
      Those with the GSTM1 null genotype had a higher incidence of neck LNM than those
      with the GSTM1 non-null genotype (P = 0.01). Patients with the GSTM1/GSTT1 null
      genotype appeared to have later onset and a higher incidence of neck LNM than
      those carrying the opposite genotype. CONCLUSION: The GST genotypes may be
      important markers for the age of onset and risk of metastasis in OSCC. The data
      also suggest that the various GST isoforms may be differentially involved in
      development or progression of OSCC.

PMID- 16091115
TI  - Cleavage of nucleolin and AgNOR proteins during apoptosis induced by anticancer
      drugs in human salivary gland cells.
AB  - BACKGROUND: To investigate the behavior of nuclear proteins in apoptosis induced
      by anticancer drugs in cultured human salivary gland (HSG) cells. METHODS:
      Dynamic alternations of nucleolin and argyrophilic nucleolar organizer region
      (AgNOR) proteins in anticancer drug-induced apoptosis of HSG cells and in a cell
      free apoptotic system were examined using Western blot analysis and
      immunocytochemical method. RESULTS: The 110-kDa form of nucleolin and AgNOR
      protein decreased and the 80- and 95-kDa forms appeared during apoptosis in HSG
      cells and in a cell-free apoptotic system. In addition, the induction of DNA
      ladder formation coincided with the appearance of alternation of nucleolin and
      AgNOR proteins in a cell-free apoptosis. Nucleolin diffusely spread out into the
      nuclear material in the apoptotic body of HSG cells. CONCLUSIONS: The present
      results indicate that alternations of nucleolin and AgNOR proteins are associated
      with the induction of DNA fragmentation and the final active phase of apoptosis
      induced by anticancer drugs in malignant salivary gland cells.

PMID- 16091116
TI  - Late effects of chronic graft-vs.-host disease in minor salivary glands.
AB  - BACKGROUND: The established pathologic criteria for minor salivary gland (MSG)
      involvement in chronic graft-vs.-host disease (cGVHD) could play a role in
      monitoring response to therapy. METHODS: We evaluated MSG sequential biopsies
      during cGVHD therapy in 14 allogeneic bone marrow transplantation (BMT) patients.
      Nine patients that did not develop GVHD after BMT entered the control group.
      Biopsies were examined using hematoxylin-eosin, Periodic acid-Schiff (PAS) and
      leukocyte common antigen staining. RESULTS: A significant loss of PAS+ acinar
      volume was observed at the diagnosis of cGVHD as much as at the end of treatment
      when compared with the control group. In the second evaluation, the inflammatory
      infiltrate was still greater than control group. CONCLUSIONS: The results suggest
      that persistent xerostomia after cGVHD treatment is because of maintenance of
      lymphocytic infiltrate and consequent absence of MSG secretory unit recovery.
      This data may be useful to provide improved insight into the histopathology of
      this organ involvement.

PMID- 16091117
TI  - Serotonin transporter gene polymorphism (5-HTTLPR) in patients with recurrent
      aphthous stomatitis.
AB  - BACKGROUND: Considerable evidence indicates that serotonergic mechanisms,
      particularly the serotonin transporter (5-HTT) may be involved in psychological
      alterations. Recent findings have demonstrated that depression and stress are
      influenced by polymorphism of the promoter region of 5-HTT (5-HTTLPR) and that
      the short allele (S) is associated with reduced transcriptional efficiency
      resulting in reduced serotonin expression and uptake. As psychological and
      genetic factors have been implicated in the pathogenesis of recurrent aphthous
      stomatitis (RAS), the purpose of the present study was to investigate 5-HTTLPR
      polymorphism in patients with RAS compared with control subjects. METHODS: Sixty
      nine consecutive subjects affected by minor and major forms of RAS and 70 healthy
      volunteers were genotyped at 5-HTTLPR. The chi-square test was used for
      statistical analysis. RESULTS: A significant increase in the genotype of SS (P =
      0.05) and of the allele S (P = 0.04) in the group of RAS were observed.
      CONCLUSION: Our findings demonstrate that RAS patients have a tendency to show
      polymorphism associated with anxiety-related traits.

PMID- 16091118
TI  - Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific
      modes revealed by immunohistochemistry and in situ hybridization.
AB  - BACKGROUND: Oral submucous fibrosis (OSF) is a chewing habit-related pre
      cancerous condition of the oral mucosa affecting predominantly south Asians. It
      is histopathologically characterized by epithelial atrophy and fibrosis of the
      subepithelial connective tissue. Fibrosis extends all the way into the muscle
      layer, leading to difficulty in mouth opening. However, the dynamics of
      extracellular matrix (ECM) remodeling with OSF progression is largely unknown.
      METHODS: Forty biopsy specimens of OSF and 10 of normal buccal mucosa were
      examined for expression/deposition modes of eight ECM molecules by
      histochemistry, immunohistochemistry, and in situ hybridization. RESULTS: In the
      early stage of OSF, tenascin, perlecan, fibronectin, collagen type III were
      characteristically enhanced in the lamina propria and the submucosal layer. In
      the intermediate stage, the ECM molecules mentioned above and elastin were
      extensively and irregularly deposited around muscle fibers. In the advanced
      stage, such ECM depositions decreased and were entirely replaced with collagen
      type I only. Their gene expression levels varied with progression of fibrosis,
      but the mRNA signals were confirmed in fibroblasts in the submucosal fibrotic
      areas. CONCLUSIONS: The results indicate that the ECM remodeling steps in OSF are
      similar to each phase of usual granulation tissue formation. Restricted mouth
      opening may be a result of loss of variety of ECM molecules including elastin
      into the homogeneity of collagen type I replacing muscle fibers.

PMID- 16091119
TI  - Pemphigus mimicking aphthous stomatitis.
AB  - BACKGROUND: The aim of this report is to highlight the case that pemphigus
      vulgaris (PV) may mimic aphthous stomatitis. Pemphigus classically causes
      persistent oral ulceration. METHODS AND RESULTS: We report five patients from
      southern Europe, who presented with recurrent oral ulceration mimicking aphthous
      stomatitis, but who proved by histology, immunostaining and antibodies against
      epithelial intercellular substance to have PV. CONCLUSION: It is advisable to
      assay antibodies against desmoglein 3 in patients who appear to suffer recurrent
      aphthous stomatitis (RAS) with atypical ulceration for location and in adulthood.

PMID- 16091120
TI  - Ameloblastoma ex calcifying odontogenic cyst (dentinogenic ghost cell tumor).
AB  - Calcifying odontogenic cyst (COC) has shown to be of extensive diversity in its
      clinical and histopathological features, as well as in its biological behavior.
      In this report, a rare case is described of ameloblastoma ex COC (dentinogenic
      ghost cell tumor) and the relevant literature is briefly reviewed.

PMID- 16091121
TI  - CD4+CD25+-regulatory T cells from mouse to man.
AB  - Immunological tolerance is one of the fundamental concepts of the immune system.
      During the past decade, CD4+CD25+-regulatory T cells have emerged as key players
      in the development of tolerance to autoantigens as well as to foreign antigens.
      Still many questions remain illusive regarding the basic properties of CD4+CD25+
      regulatory T cells. This review aims to recapitulate some of the current
      understandings about the phenotype, function and clinical relevance of murine and
      human CD4+CD25+-regulatory T cells.

PMID- 16091122
TI  - The six mammalian cell entry proteins (Mce3A-F) encoded by the mce3 operon are
      expressed during in vitro growth of Mycobacterium tuberculosis.
AB  - The pathogenesis of Mycobacterium tuberculosis is largely due to its ability to
      enter and survive within human macrophages. The mammalian cell entry (mce)3
      operon is one of four homologous mce operons that encodes six putative invasin
      like exported proteins (Mce3A-F), possibly involved in entry and survival of M.
      tuberculosis inside macrophages. We have recently shown that Mce3A, Mce3D and
      Mce3E are expressed and elicit antibody responses in a majority of human subjects
      during natural infection with M. tuberculosis. In this study, we demonstrate the
      expression of Mce3A-F proteins and their mRNA during in vitro growth of M.
      tuberculosis. To demonstrate the expression of mce3A-F proteins, the antibodies
      were raised in rabbits against three pure proteins (Mce3A, Mce3D and Mce3E), and
      their specificity was checked by immunoblotting with recombinant Mce1A-F proteins
      encoded by mce1 operon. The antibodies were also generated against all the six
      Mce3 proteins, which were expressed and purified as fusion proteins with
      glutathione S-transferase (GST) as the fusion partner (GST-Mce3A-F). The
      antibodies reacted, in each case, with a protein of expected molecular mass (Mr)
      for the corresponding Mce3 protein in the cell wall fraction but not in the
      soluble fraction of in vitro-grown M. tuberculosis cells. The presence of mRNA
      for mce3A-F genes was also shown by using mce3A-F gene-specific primers, and
      total RNA isolated from in vitro-grown M. tuberculosis cells by reverse
      transcription-polymerase chain reaction (RT-PCR). Pretreatment of the RNA
      preparation with RNase A abolished amplification in RT-PCR confirming that mce3A
      F mRNA rather than genomic DNA was being amplified. The data show that Mce3A-F
      encoded by the mce3 operon are expressed during in vitro growth of M.
      tuberculosis.

PMID- 16091123
TI  - Signal pathway of cytokines produced by reactive oxygen species generated from
      phorbol myristate acetate-stimulated HMC-1 cells.
AB  - The relationship of cytokine production and reactive oxygen species (ROS)
      generated in mast cells has not been reported yet. This study aimed to examine
      the signal pathway in the production of cytokines [interleukin-8 (IL-8) and
      tumour necrosis factor-alpha (TNF-alpha)] by ROS generated from phorbol myristate
      acetate (PMA)-stimulated human mast cell line-1 cells (HMC-1). HMC-1 cells were
      stimulated with 25 ng/ml of PMA. The ROS generation and production of cytokines
      (IL-8 and TNF-alpha) were measured by fluorescence-activated cell sorter and
      enzyme-linked immunosorbent assay method, respectively. Phosphorylation of
      mitogen-activated protein kinase family (extracellular signal-regulated kinase,
      p38 and c-Jun N-terminal kinase) was detected by the Western blotting method. The
      expression of cytokine's mRNA was measured by reverse transcriptase--polymerase
      chain reaction, and the DNA-binding activity of the transcription factors
      [nuclear factor-kappaB (NF-kappaB) and activator protein-1] was detected by
      electrophoretic mobility shift assay. PMA-stimulated HMC-1 cells immediately
      generated ROS, and the generated ROS was inhibited by 1,3-dimethyl-2-thiourea
      (DMTU), but partially inhibited by catalase or N-acetyl-L-cysteine. The
      production of cytokines in PMA-stimulated HMC-1 cells reached the maximum at 3-5
      h and was inhibited by DMTU and specific kinase inhibitor for p38, SB203580. DMTU
      and SB203580 also inhibited the expressed cytokine's mRNA level and the increased
      DNA-binding activity of transcription factors, NF-kappaB in PMA-stimulated HMC-1
      cells. These data suggest that intracellular ROS generated from PMA-stimulated
      HMC-1 cells contributes to the production of inflammatory cytokines via p38
      kinase/NF-kappaB.

PMID- 16091124
TI  - Dexamethasone induces IL-10-producing monocyte-derived dendritic cells with
      durable immaturity.
AB  - It is highly desirable that immature dendritic cells (DC) used for tolerance
      induction maintain steady immature state with predominant interleukin (IL)-10
      production. In this study, we attempted to develop DC with durable immaturity and
      other tolerogenic features by using dexamethasone (Dex). We found DC derived from
      human monocytes in the presence of 10(-7) m Dex were negative for CD1a. Compared
      with control transduced DC (Ctrl-DC), Dex-DC expressed lower CD40, CD80 and CD86
      but equivalent human leucocyte antigen-DR. Both immature Dex- and Ctrl-DC did not
      express CD83. Nevertheless, upon stimulation of lipopolysaccharide (LPS) or CD40
      ligand, the expression of CD40, CD80, CD83 and CD86 was upregulated on Ctrl-DC
      but not on Dex-DC. The immaturity of Dex-DC was durable following Dex removal.
      Interestingly, Dex-DC maintained production of large amount of IL-10 and little
      IL-12 five days after Dex removed. Further study indicated that high-level IL-10
      production by Dex-DC was associated with high-level phosphorylation of
      extracellular signal-regulated kinase (ERK) as blockade of this enzyme markedly
      attenuated IL-10 production. Furthermore, Dex-DC sustained the capability of high
      phosphorylation of ERK and IL-10 production 5 days after Dex removal. In
      addition, Dex-DC had significantly lower activity in stimulating T-cell
      proliferation. Neutralization of IL-10, to some extent, promoted DC maturation
      activated by LPS, as well as T-cell stimulatory activity of Dex-DC. The above
      findings suggest that IL-10-producing Dex-DC with durable immaturity are
      potentially useful for induction of immune tolerance.

PMID- 16091125
TI  - Phenotypic study of peripheral blood lymphocytes and humoral immune response in
      Helicobacter pylori infection according to age.
AB  - There are differences between children and adults in certain aspects of the
      Helicobacter pylori (HP) infection, among them the lower titre of IgG antibodies
      anti-HP in the former group. Thus, we investigated by means of flow cytometry
      CD4+/CD3+ (CD4+T), CD8+/CD3+ (CD8+T) and CD19+/CD3- (B) cells, activation/co
      stimulatory markers (CD4+/HLA-DR+, CD4+/CD28+, CD8+/HLA-DR+ and CD8+/CD28+) and
      by means of ELISA IgG anti-HP antibodies in the peripheral blood from HP-positive
      and -negative children and adults. An increased CD4+/CD28+ and CD8+/CD28+
      percentage and number of CD4+/CD3+ cells were seen in infected adults.
      Conversely, no difference was observed between infected and noninfected children,
      but when they were stratified by age, an increased CD4+/CD28+ cell percentage was
      seen in the HP-positive group older than 10 years. The mean level of IgG anti-HP
      was lower in younger infected children, increased with age and correlated with
      CD4+ cells. Our data suggest that the immune response to HP infection vary
      according to the age. Low percentage of activated CD4+ cell may contribute to the
      lower level of serum IgG anti-HP observed in younger infected children. In
      addition, the CD4+ cell participation during the infection seems to begin after
      10 years old, when the immune response becomes similar to that seen in adults.

PMID- 16091126
TI  - Ethnic variations of IL-10 polymorphisms in a Sami and Norwegian population.
AB  - Interleukin-10 (IL-10) production is genetically determined and influenced by
      different polymorphisms in the promoter region of IL-10. These polymorphisms may
      contribute to the risk and clinical outcome of various infectious and
      immunological-related diseases. The Samis are the aboriginal inhabitants of
      Norway and Fennoscandinavia and are ethnically different from the Norwegians.
      Different distribution of various immune-related diseases among the Samis
      compared with Norwegians have been reported. This is the first study to evaluate
      the distribution of IL-10 polymorphisms in the Sami population. Two hundred
      healthy Samis were genotyped for polymorphisms in the promoter region of IL-10 at
      region -1082 (G/A), -819 (T/C) and -592 (A/C). The allele frequencies, genotypes
      and haplotypes were compared with 187 healthy Norwegians. A significantly higher
      number of the Samis than the Norwegians had the ATA/ATA genotype, whereas the
      Norwegians displayed a higher frequency of the GCC/GCC genotype (P=0.0057). There
      was a significant difference in haplotypes in the two populations with a
      P=0.0024. These findings may be important for the distribution and clinical
      outcome of various infectious and immune-related disorders in the two
      populations.

PMID- 16091127
TI  - Leukaemia-derived dendritic cells can be generated from blood or bone marrow
      cells from patients with myelodysplasia: a methodological approach under serum
      free culture conditions.
AB  - Functional dendritic cells (DC) are professional antigen-presenting cells (APC)
      and can be generated in vitro from healthy as well as from leukaemic cells from
      AML patients giving rise to APC of leukaemic origin presenting leukaemic
      antigens. In a comparative methodological analysis of 50 AML samples, we could
      already show that leukaemia-derived DC can regularly be generated under serum
      free culture conditions. In this study, we describe the generation and
      characterization of DC from different mononuclear cell (MNC) fractions from 24
      myelodysplastic syndrome (MDS) patients under those different serum-free culture
      conditions, determine the optimal culture conditions and compare the results with
      that from 23 healthy donors. In parallel cultures, we compared DC harvests after
      7- or 14-day culture, with total or adherent MNC or T-cell-depleted MNC or PB or
      BM-MNC, thawn or fresh MNC, in Xvivo or CellGro serum-free media, +/-10%
      autologous plasma or +/-FL. In detail, we could show that MDS-DC harvests
      compared to healthy DC were higher after 10- to 14-day culture; total or adherent
      PB or BM-MNC fractions yield comparable DC counts; however, from MACS-depleted
      MNC fractions or thawn MNC lower DC counts can be generated. Whereas the addition
      of FL increases the DC harvest, the addition of autologous plasma in many cases
      has inhibitory influence on DC maturation, CellGro and Xvivo media yield
      comparable DC counts. Optimal harvest of vital and mature DC from MDS samples was
      obtained with a GM-CSF, IL-4, FL and TNF-alpha containing serum-free Xvivo medium
      after 10-14 days of culture (18/26% DC; 54/64% vital DC; 59/51% mature DC were
      generated from MDS/healthy MNC samples). Surface marker profiles (e.g.
      costimulatory antigen expression) of DC obtained from MDS samples were comparable
      with that of healthy DC. The leukaemic derivation of MDS-DC was demonstrated by
      the persistence of the clonal cytogenetic aberration in the DC or by coexpression
      of leukaemic antigens on DC. Autologous T-cell activation of leukaemia-derived DC
      was demonstrated in cases with MDS. Autologous T cells proliferate and upregulate
      DC-contact-relevant antigens. We are the first who demonstrate that the
      generation of leukaemia-derived DC is feasible not only in AML but also in MDS
      under serum-free culture conditions giving rise to DC with comparable
      characteristics as healthy DC and offering an antileukaemia-directed
      immunotherapeutical vaccination strategy in AML and MDS.

PMID- 16091128
TI  - Leukemia-derived dendritic cells can be generated from blood or bone marrow cells
      from patients with acute myeloid leukaemia: a methodological approach under serum
      free culture conditions.
AB  - Functional dendritic cells (DC) are professional antigen-presenting cells (APC)
      and can be generated in vitro from healthy as well as from leukaemic cells from
      acute myeloid leukemia (AML) patients giving rise to APC of leukaemic origin
      presenting leukaemic antigens. We describe the generation and characterization of
      DC from different mononuclear cell (MNC) fractions from 50 AML patients under
      different serum-free culture conditions, determine the optimal culture conditions
      and compare the results with that from 23 healthy donors. In parallel cultures,
      we compared DC harvests after 7- or 14-day culture, with total or adherent MNC or
      T-cell depleted MNC or peripheral blood (PB) or bone marrow-MNC (BM-MNC), thawn
      or fresh MNC, in Xvivo or CellGro serum-free media, +/-10% autologous plasma or
      +/-FL. In detail, we could show that AML-DC harvests were higher after 10-14 days
      culture (healthy DC: 7 days); total or adherent PB or BM-MNC fractions yield
      comparable DC counts, however, from magnetic cell sorting (MACS)-depleted MNC
      fractions or thawn MNC lower DC counts can be generated. Whereas the addition of
      FL increases the DC harvest, the addition of autologous plasma in many cases has
      inhibitory influence on DC maturation. CellGro and Xvivo media yield comparable
      DC counts. Optimal harvest of vital and mature DC from AML samples was obtained
      with a granulocyte/macrophage-colony stimulating factor, interleukin-4, FL and
      tumour necrosis factor-alpha-containing serum-free Xvivo medium after 10-14 days
      of culture (36/26% DC; 38/64% vital DC; 46/51% mature DC were generated from
      AML/healthy MNC samples). Surface marker profiles (e.g. costimulatory antigen
      expressing) of DC obtained from AML samples were comparable with that of healthy
      DC. The leukaemic derivation of AML-DC was demonstrated by the persistence of the
      clonal cytogenetic aberration in the DC or by coexpression of leukaemic antigens
      on DC. Autologous T-cell activation of leukaemia-derived DC was demonstrated in
      cases with AML. Autologous T cells proliferate and upregulate DC-contact-relevant
      antigens. We demonstrate that the generation of leukaemia-derived DC is feasable
      in AML under serum-free culture conditions giving rise to DC with comparable
      characteristics as healthy DC and offering an anti-leukaemia-directed
      immunotherapeutical vaccination strategy in AML.

PMID- 16091129
TI  - On the responses of Zinkernagel and Hengartner: an invitation to join the fray.

PMID- 16091130
TI  - The definition of disabling fatigue in children and adolescents.
AB  - BACKGROUND: Disabling fatigue is the main illness related reason for prolonged
      absence from school. Although there are accepted criteria for diagnosing chronic
      fatigue in adults, it remains uncertain as to how best to define disabling
      fatigue and Chronic Fatigue Syndrome (CFS) in children and adolescents. In this
      population-based study, the aim was to identify children who had experienced an
      episode of disabling fatigue and examine the clinical and demographic differences
      between those individuals who fulfilled a narrow definition of disabling fatigue
      and those who fulfilled broader definitions of disabling fatigue. METHODS:
      Participants (aged 8-17 years) were identified from a population-based twin
      register. Parent report was used to identify children who had ever experienced a
      period of disabling fatigue. Standardised telephone interviews were then
      conducted with the parents of these affected children. Data on clinical and
      demographic characteristics, including age of onset, gender, days per week
      affected, hours per day spent resting, absence from school, comorbidity with
      depression and a global measure of impairment due to the fatigue, were examined.
      A narrow definition was defined as a minimum of 6 months disabling fatigue plus
      at least 4 associated symptoms, which is comparable to the operational criteria
      for CFS in adults. Broader definitions included those with at least 3 months of
      disabling fatigue and 4 or more of the associated symptoms and those with simply
      a minimum of 3 months of disabling fatigue. Groups were mutually exclusive.
      RESULTS: Questionnaires were returned by 1468 families (65% response rate) and
      telephone interviews were completed on 99 of the 129 participants (77%) who had
      experienced fatigue. There were no significant differences in demographic and
      clinical characteristics or levels of impairment between those who fulfilled the
      narrower definition and those who fulfilled the broader definitions. The only
      exception was the reported number of days per week that the child was affected by
      the fatigue. All groups demonstrated evidence of substantial impairment
      associated with the fatigue. CONCLUSION: Children and adolescents who do not
      fulfil the current narrow definition of CFS but do suffer from disabling fatigue
      show comparable and substantial impairment. In primary care settings, a broader
      definition of disabling fatigue would improve the identification of impaired
      children and adolescents who require support.

PMID- 16091131
TI  - Predictors of primary breast cancers responsiveness to preoperative
      epirubicin/cyclophosphamide-based chemotherapy: translation of microarray data
      into clinically useful predictive signatures.
AB  - BACKGROUND: Our goal was to identify gene signatures predictive of response to
      preoperative systemic chemotherapy (PST) with epirubicin/cyclophosphamide (EC) in
      patients with primary breast cancer. METHODS: Needle biopsies were obtained pre
      treatment from 83 patients with breast cancer and mRNA was profiled on Affymetrix
      HG-U133A arrays. Response ranged from pathologically confirmed complete remission
      (pCR), to partial remission (PR), to stable or progressive disease, "No Change"
      (NC). A primary analysis was performed in breast tissue samples from 56 patients
      and 5 normal healthy individuals as a training cohort for predictive marker
      identification. Gene signatures identifying individuals most likely to respond
      completely to PST-EC were extracted by combining several statistical methods and
      filtering criteria. In order to optimize prediction of non responding tumors
      Student's t-test and Wilcoxon test were also applied. An independent cohort of 27
      patients was used to challenge the predictive signatures. A k-Nearest neighbor
      algorithm as well as two independent linear partial least squares determinant
      analysis (PLS-DA) models based on the training cohort were selected for
      classification of the test samples. The average specificity of these predictions
      was greater than 74% for pCR, 100% for PR and greater than 62% for NC. All three
      classification models could identify all pCR cases. RESULTS: The differential
      expression of 59 genes in the training and the test cohort demonstrated
      capability to predict response to PST-EC treatment. Based on the training cohort
      a classifier was constructed following a decision tree. First, a transcriptional
      profile capable to distinguish cancerous from normal tissue was identified. Then,
      a "favorable outcome signature" (31 genes) and a "poor outcome signature" (26
      genes) were extracted from the cancer specific signatures. This stepwise
      implementation could predict pCR and distinguish between NC and PR in a
      subsequent set of patients. Both PLS-DA models were implemented to discriminate
      all three response classes in one step. CONCLUSION: In this study signatures were
      identified capable to predict clinical outcome in an independent set of primary
      breast cancer patients undergoing PST-EC.

PMID- 16091132
TI  - The complete mitochondrial genome of the stomatopod crustacean Squilla mantis.
AB  - BACKGROUND: Animal mitochondrial genomes are physically separate from the much
      larger nuclear genomes and have proven useful both for phylogenetic studies and
      for understanding genome evolution. Within the phylum Arthropoda the subphylum
      Crustacea includes over 50,000 named species with immense variation in body plans
      and habitats, yet only 23 complete mitochondrial genomes are available from this
      subphylum. RESULTS: I describe here the complete mitochondrial genome of the
      crustacean Squilla mantis (Crustacea: Malacostraca: Stomatopoda). This 15994
      nucleotide genome, the first described from a hoplocarid, contains the standard
      complement of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA
      genes, and a non-coding AT-rich region that is found in most other metazoans. The
      gene order is identical to that considered ancestral for hexapods and
      crustaceans. The 70% AT base composition is within the range described for other
      arthropods. A single unusual feature of the genome is a 230 nucleotide non-coding
      region between a serine transfer RNA and the nad1 gene, which has no apparent
      function. I also compare gene order, nucleotide composition, and codon usage of
      the S. mantis genome and eight other malacostracan crustaceans. A translocation
      of the histidine transfer RNA gene is shared by three taxa in the order Decapoda,
      infraorder Brachyura; Callinectes sapidus, Portunus trituberculatus and
      Pseudocarcinus gigas. This translocation may be diagnostic for the Brachyura. For
      all nine taxa nucleotide composition is biased towards AT-richness, as expected
      for arthropods, and is within the range reported for other arthropods. Codon
      usage is biased, and much of this bias is probably due to the skew in nucleotide
      composition towards AT-richness. CONCLUSION: The mitochondrial genome of Squilla
      mantis contains one unusual feature, a 230 base pair non-coding region has so far
      not been described in any other malacostracan. Comparisons with other
      Malacostraca show that all nine genomes, like most other mitochondrial genomes,
      share a bias toward AT-richness and a related bias in codon usage. The nine
      malacostracans included in this analysis are not representative of the diversity
      of the class Malacostraca, and additional malacostracan sequences would surely
      reveal other unusual genomic features that could be useful in understanding
      mitochondrial evolution in this taxon.

PMID- 16091133
TI  - Reduced expression of multiple gap junction proteins is a feature of cervical
      dysplasia.
AB  - Cervical dysplasia is a premalignant lesion associated with human papillomavirus
      (HPV) infection which, over time, can turn cancerous. Previous studies have
      indicated that loss of gap junctions may be a feature of cervical cancer and
      premalignant dysplasia. Loss of the gap junction protein connexin43 has been
      demonstrated in dysplastic cervix, but other connexins have not been
      investigated. In contrast we previously showed that HPV-associated cutaneous
      warts--and other hyperproliferative skin conditions--display a dramatic
      upregulation of certain connexins, in particular connexin26. By performing
      immunofluorescence staining after antigen retrieval of paraffin-embedded cervical
      tissue samples, this study reports for the first time that connexin26 and
      connexin30, in addition to connexin43, are expressed in differentiating cells of
      normal human cervical epithelia. Moreover, in dysplastic ectocervix, all
      connexins studied display a dramatic loss of expression compared to adjacent
      normal epithelia. The role of connexins in keratinocyte differentiation and
      carcinogenesis is discussed.

PMID- 16091134
TI  - Reflex control of the spine and posture: a review of the literature from a
      chiropractic perspective.
AB  - OBJECTIVE: This review details the anatomy and interactions of the postural and
      somatosensory reflexes. We attempt to identify the important role the nervous
      system plays in maintaining reflex control of the spine and posture. We also
      review, illustrate, and discuss how the human vertebral column develops,
      functions, and adapts to Earth's gravity in an upright position. We identify
      functional characteristics of the postural reflexes by reporting previous
      observations of subjects during periods of microgravity or weightlessness.
      BACKGROUND: Historically, chiropractic has centered around the concept that the
      nervous system controls and regulates all other bodily systems; and that
      disruption to normal nervous system function can contribute to a wide variety of
      common ailments. Surprisingly, the chiropractic literature has paid relatively
      little attention to the importance of neurological regulation of static upright
      human posture. With so much information available on how posture may affect
      health and function, we felt it important to review the neuroanatomical
      structures and pathways responsible for maintaining the spine and posture.
      Maintenance of static upright posture is regulated by the nervous system through
      the various postural reflexes. Hence, from a chiropractic standpoint, it is
      clinically beneficial to understand how the individual postural reflexes work, as
      it may explain some of the clinical presentations seen in chiropractic practice.
      METHOD: We performed a manual search for available relevant textbooks, and a
      computer search of the MEDLINE, MANTIS, and Index to Chiropractic Literature
      databases from 1970 to present, using the following key words and phrases:
      "posture," "ocular," "vestibular," "cervical facet joint," "afferent,"
      "vestibulocollic," "cervicocollic," "postural reflexes," "spaceflight,"
      "microgravity," "weightlessness," "gravity," "posture," and "postural." Studies
      were selected if they specifically tested any or all of the postural reflexes
      either in Earth's gravity or in microgravitational environments. Studies testing
      the function of each postural component, as well as those discussing postural
      reflex interactions, were also included in this review. DISCUSSION: It is quite
      apparent from the indexed literature we searched that posture is largely
      maintained by reflexive, involuntary control. While reflexive components for
      postural control are found in skin and joint receptors, somatic graviceptors, and
      baroreceptors throughout the body, much of the reflexive postural control
      mechanisms are housed, or occur, within the head and neck region primarily. We
      suggest that the postural reflexes may function in a hierarchical fashion. This
      hierarchy may well be based on the gravity-dependent or gravity-independent
      nature of each postural reflex. Some or all of these postural reflexes may
      contribute to the development of a postural body scheme, a conceptual internal
      representation of the external environment under normal gravity. This model may
      be the framework through which the postural reflexes anticipate and adapt to new
      gravitational environments. CONCLUSION: Visual and vestibular input, as well as
      joint and soft tissue mechanoreceptors, are major players in the regulation of
      static upright posture. Each of these input sources detects and responds to
      specific types of postural stimulus and perturbations, and each region has
      specific pathways by which it communicates with other postural reflexes, as well
      as higher central nervous system structures. This review of the postural reflex
      structures and mechanisms adds to the growing body of posture rehabilitation
      literature relating specifically to chiropractic treatment. Chiropractic interest
      in these reflexes may enhance the ability of chiropractic physicians to treat and
      correct global spine and posture disorders. With the knowledge and understanding
      of these postural reflexes, chiropractors can evaluate spinal configurations not
      only from a segmental perspective, but can also determine how spinal dysfunction
      may be the ultimate consequence of maintaining an upright posture in the presence
      of other postural deficits. These perspectives need to be explored in more
      detail.

PMID- 16091135
TI  - Menstrual function among women exposed to polybrominated biphenyls: a follow-up
      prevalence study.
AB  - BACKGROUND: Alteration in menstrual cycle function is suggested among rhesus
      monkeys and humans exposed to polybrominated biphenyls (PBBs) and structurally
      similar polychlorinated biphenyls (PCBs). The feedback system for menstrual cycle
      function potentially allows multiple pathways for disruption directly through the
      hypothalamic-pituitary-ovarian axis and indirectly through alternative
      neuroendocrine axes. METHODS: The Michigan Female Health Study was conducted
      during 1997-1998 among women in a cohort exposed to PBBs in 1973. This study
      included 337 women with self-reported menstrual cycles of 20-35 days (age range:
      24-56 years). Current PBB levels were estimated by exponential decay modeling of
      serum PBB levels collected from 1976-1987 during enrollment in the Michigan PBB
      cohort. Linear regression models for menstrual cycle length and the logarithm of
      bleed length used estimated current PBB exposure or enrollment PBB exposure
      categorized in tertiles, and for the upper decile. All models were adjusted for
      serum PCB levels, age, body mass index, history of at least 10% weight loss in
      the past year, physical activity, smoking, education, and household income.
      RESULTS: Higher levels of physical activity were associated with shorter bleed
      length, and increasing age was associated with shorter cycle length. Although no
      overall association was found between PBB exposure and menstrual cycle
      characteristics, a significant interaction between PBB exposures with past year
      weight loss was found. Longer bleed length and shorter cycle length were
      associated with higher PBB exposure among women with past year weight loss.
      CONCLUSION: This study suggests that PBB exposure may impact ovarian function as
      indicated by menstrual cycle length and bleed length. However, these associations
      were found among the small number of women with recent weight loss suggesting
      either a chance finding or that mobilization of PBBs from lipid stores may be
      important. These results should be replicated with larger numbers of women
      exposed to similar lipophilic compounds.

PMID- 16091136
TI  - PPARalpha downregulates airway inflammation induced by lipopolysaccharide in the
      mouse.
AB  - BACKGROUND: Inflammation is a hallmark of acute lung injury and chronic airway
      diseases. In chronic airway diseases, it is associated with profound tissue
      remodeling. Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a
      ligand-activated transcription factor, that belongs to the nuclear receptor
      family. Agonists for PPARalpha have been recently shown to reduce
      lipopolysaccharide (LPS)- and cytokine-induced secretion of matrix
      metalloproteinase-9 (MMP-9) in human monocytes and rat mesangial cells,
      suggesting that PPARalpha may play a beneficial role in inflammation and tissue
      remodeling. METHODS: We have investigated the role of PPARalpha in a mouse model
      of LPS-induced airway inflammation characterized by neutrophil and macrophage
      infiltration, by production of the chemoattractants, tumor necrosis factor-alpha
      (TNF-alpha), keratinocyte derived-chemokine (KC), macrophage inflammatory protein
      2 (MIP-2) and monocyte chemoattractant protein-1 (MCP-1), and by increased MMP-2
      and MMP-9 activity in bronchoalveolar lavage fluid (BALF). The role of PPARalpha
      in this model was studied using both PPARalpha-deficient mice and mice treated
      with the PPARalpha activator, fenofibrate. RESULTS: Upon intranasal exposure to
      LPS, PPARalpha-/- mice exhibited greater neutrophil and macrophage number in
      BALF, as well as increased levels of TNF-alpha, KC, MIP-2 and MCP-1, when
      compared to PPARalpha+/+ mice. PPARalpha-/- mice also displayed enhanced MMP-9
      activity. Conversely, fenofibrate (0.15 to 15 mg/day) dose-dependently reduced
      the increase in neutrophil and macrophage number induced by LPS in wild-type
      mice. In animals treated with 15 mg/day fenofibrate, this effect was associated
      with a reduction in TNF-alpha, KC, MIP-2 and MCP-1 levels, as well as in MMP-2
      and MMP-9 activity. PPARalpha-/- mice treated with 15 mg/day fenofibrate failed
      to exhibit decreased airway inflammatory cell infiltrate, demonstrating that
      PPARalpha mediates the anti-inflammatory effect of fenofibrate. CONCLUSION: Using
      both genetic and pharmacological approaches, our data clearly show that PPARalpha
      downregulates cell infiltration, chemoattractant production and enhanced MMP
      activity triggered by LPS in mouse lung. This suggests that PPARalpha activation
      may have a beneficial effect in acute or chronic inflammatory airway disorders
      involving neutrophils and macrophages.

PMID- 16091137
TI  - Effect on survey response rate of hand written versus printed signature on a
      covering letter: randomised controlled trial [ISRCTN67566265].
AB  - BACKGROUND: It is important that response rates to postal surveys are as high as
      possible to ensure that the results are representative and to maximise
      statistical power. Previous research has suggested that any personalisation of
      approach helps to improve the response rate. This experiment tested whether
      personalising questionnaires by hand signing the covering letter improved the
      response rate compared with a non-personalised group where the investigator's
      signature on the covering letter was scanned into the document and printed.
      METHODS: Randomised controlled trial. Questionnaires about surgical techniques of
      caesarean section were mailed to 3,799 Members and Fellows of the Royal College
      of Obstetricians and Gynaecologists resident in the UK. Individuals were randomly
      allocated to receive a covering letter with either a computer printed signature
      or a hand written signature. Two reminders were sent to non-respondents. The
      outcome measures were the proportion of questionnaires returned and their time to
      return. RESULTS: The response rate was 79.1% (1506/1905) in the hand-signed group
      and 78.4% (1484/1894) in the scanned and printed signature group. There was no
      detectable difference between the groups in response rate or time taken to
      respond. CONCLUSION: No advantage was detected to hand signing the covering
      letter accompanying a postal questionnaire to health professionals.

PMID- 16091138
TI  - Fast, visual specialization for reading in English revealed by the topography of
      the N170 ERP response.
AB  - BACKGROUND: N170 effects associated with visual words may be related to
      perceptual expertise effects that have been demonstrated for faces and other
      extensively studied classes of visual stimuli. Although face and other object
      expertise effects are typically bilateral or right-lateralized, the spatial
      topography of reading-related N170 effects are often left-lateralized, providing
      potential insights into the unique aspects of reading-related perceptual
      expertise. METHODS: Extending previous research in German, we use a high-density
      channel array to characterize the N170 topography for reading-related perceptual
      expertise in English, a language with inconsistent spelling-to-sound mapping.
      N170 effects related to overall reading-related expertise are defined by
      contrasting responses to visual words versus novel symbol strings. By contrasting
      each of these conditions to pseudowords, we examined how this reading-related
      N170 effect generalizes to well-ordered novel letter strings. RESULTS: A sample
      by-sample permutation test computed on word versus symbol ERP topographies
      revealed differences during two time windows corresponding to the N170 and P300
      components. Topographic centroid analysis of the word and symbol N170
      demonstrated significant differences in both left-right as well as inferior
      superior dimensions. Words elicited larger N170 negativities than symbols at
      inferior occipito-temporal channels, with the maximal effect over left inferior
      regions often unsampled in conventional electrode montages. Further contrasts
      produced inferior-superior topographic effects for the pseudoword-symbol
      comparison and left-lateralized topographic effects for the word-pseudoword
      comparison. CONCLUSION: Fast specialized perception related to reading experience
      produces an N170 modulation detectable across different EEG systems and different
      languages. Characterization of such effects may be improved by sampling with
      greater spatial frequency recordings that sample inferior regions. Unlike in
      German, reading-related expertise effects in English produced only partial
      generalization in N170 responses to novel pseudowords. The topographic inferior
      superior N170 differences may reflect general perceptual expertise for
      orthographic strings, as it was found for words and pseudowords across both
      languages. The topographic left-right N170 difference between words and
      pseudowords was only found in English, and may suggest that ambiguity in
      pronunciating novel pseudowords due to inconsistency in spelling-to-sound mapping
      influences early stages of letter string processing.

PMID- 16091139
TI  - The cost-effectiveness of neonatal screening for cystic fibrosis: an analysis of
      alternative scenarios using a decision model.
AB  - BACKGROUND: The use of neonatal screening for cystic fibrosis is widely debated
      in the United Kingdom and elsewhere, but the evidence available to inform policy
      is limited. This paper explores the cost-effectiveness of adding screening for
      cystic fibrosis to an existing routine neonatal screening programme for
      congenital hypothyroidism and phenylketonuria, under alternative scenarios and
      assumptions. METHODS: The study is based on a decision model comparing screening
      to no screening in terms of a number of outcome measures, including diagnosis of
      cystic fibrosis, life-time treatment costs, life years and QALYs gained. The
      setting is a hypothetical UK health region without an existing neonatal screening
      programme for cystic fibrosis. RESULTS: Under initial assumptions, neonatal
      screening (using an immunoreactive trypsin/DNA two stage screening protocol)
      costs 5,387 pound sterling per infant diagnosed, or 1.83 pound sterling per
      infant screened (1998 costs). Neonatal screening for cystic fibrosis produces an
      incremental cost-effectiveness of 6,864 pound sterling per QALY gained, in our
      base case scenario (an assumed benefit of a 6 month delay in the emergence of
      symptoms). A difference of 11 months or more in the emergence of symptoms (and
      mean survival) means neonatal screening is both less costly and produces better
      outcomes than no screening. CONCLUSION: Neonatal screening is expensive as a
      method of diagnosis. Neonatal screening may be a cost-effective intervention if
      the hypothesised delays in the onset of symptoms are confirmed. Implementing both
      antenatal and neonatal screening would undermine potential economic benefits,
      since a reduction in the birth incidence of cystic fibrosis would reduce the cost
      effectiveness of neonatal screening.

PMID- 16091140
TI  - Proanthocyanidins, from Ribes nigrum leaves, reduce endothelial adhesion
      molecules ICAM-1 and VCAM-1.
AB  - BACKGROUND: The effects of proanthocyanidins (PACs), isolated from blackcurrant
      (Ribes nigrum L.) leaves, on neutrophil accumulation during inflammatory
      processes were investigated in vivo and in vitro. METHODS: In vivo studies were
      performed using carrageenin-induced pleurisy in rats pre-treated with PACs.
      Exudate volume and PMNs accumulation were measured. Leukocyte cell adhesion
      molecules (LFA-1, Mac-1 and VLA-4) mobilization in circulating granulocytes were
      analysed by flow cytometry and endothelial cell adhesion molecules (ICAM-1 and
      VCAM-1) were detected by immunohistochemistry on lung sections. In vitro studies
      were conducted on endothelial LT2 cells, stimulated with TNF-alpha, to evaluate
      ICAM-1, IL-8 and VEGF mRNA expression upon PACs treatment. Data sets were
      examined by one-way analysis of variance (ANOVA) followed by a Scheffe post-hoc
      test. RESULTS: Pretreatment of the animals with PACs (10, 30 and 60 mg/kg)
      inhibited dose-dependently carrageenin-induced pleurisy in rats by reducing
      pleural exudate formation and PMNs infliltration. Leukocyte cell adhesion
      molecules mobilization was not down-regulated on granulocytes by PACs.
      Immunohistochemistry on lung sections showed a decreased production of
      endothelial cell adhesion molecules. In vitro experiments demonstrated that PACs
      were able to significantly inhibit ICAM-1 but not IL-8 and VEGF165 mRNA
      expression. Moreover, VEGF121 mRNA expression was dose-dependently enhanced.
      CONCLUSION: This study provides evidence to support the anti-inflammatory
      activity of proanthocyanidins is related to an inhibition of leukocyte
      infiltration which can be explained at least in part by a down-regulation of
      endothelial adhesion molecules, ICAM-1 and VCAM-1 and that these compounds are
      capable of modulating TNF-alpha-induced VEGF transcription.

PMID- 16091141
TI  - Neuropsychological measures of attention and memory function in schizophrenia:
      relationships with symptom dimensions and serum monoamine activity.
AB  - BACKGROUND: Some clinical symptoms or cognitive functions have been related to
      the overall state of monoamine activity in patients with schizophrenia, (e.g.
      inverse correlation of the dopamine metabolite HVA with delusions or visual
      masking performance). However, profiles (as presented here) of the relations of
      the activity of dopamine, noradrenaline and serotonin to neuropsychologic
      (dys)functions in major patient sub-groups with their very different symptomatic
      and cognitive characteristics have not been reported. METHODS: Serum measures of
      dopamine, noradrenaline and serotonin turnover were examined by regression
      analyses for the prediction of performance on 10 neuropsychological measures
      reflecting left- and right-hemispheric and frontal-, parietal- and temporal-lobe
      function in 108 patients with schizophrenia and 63 matched controls. The
      neuropsychological battery included tests of verbal fluency, Stroop interference,
      trail-making, block-design, Mooney faces recognition, picture-completion,
      immediate and delayed visual and verbal recall. Paranoid and nonparanoid
      subgroups were based on ratings from the Positive and Negative Syndrome Scale
      (PANSS). Groups with high and low ratings of ideas-of-reference and thought
      disorder were formed from a median split on the Scale for Assessment of Positive
      Symptoms (SAPS). RESULTS: Verbal-fluency and Stroop-interference (left frontal
      and fronto-cingulate function) were negatively associated with noradrenergic
      turnover in nonparanoid and thought-disordered patients. High dopamine turnover
      related to speeded trail-making (frontal modulation of set switching) in those
      with many ideas-of-reference. In contrast, low dopamine turnover predicted poor
      recall in nonparanoid patients and those with little thought disorder. Serotonin
      metabolism did not independently contribute to the prediction any measure of
      cognitive performance. But, with regard to the relative activity between
      monoaminergic systems, increased HVA/5-HIAA ratios predicted visual-reproduction
      and Mooney's face-recognition performance (right-hemisphere functions) in highly
      symptomatic patients. Decreased HVA/MHPG predicted non-verbal recall. CONCLUSION:
      Clinical state and function are differentially sensitive to overall levels of
      monoamine activity. In particular, right-lateralised cerebral function was
      sensitive to the relative activities of the monoamines. Increased noradrenergic
      activity was associated with enhanced frontal but impaired temporal lobe function
      in nonparanoid syndromes. Low dopaminergic activity predicted poor attentional
      set control in those with ideas-of-reference, but poor recall in nonparanoid
      patients. These data, especially the HVA/5-HIAA ratios, provide a basis for
      planning the nature of antipsychotic treatment aimed at patient specific symptom
      dimensions and cognitive abilities.

PMID- 16091142
TI  - Reversal of high dietary fructose-induced PPARalpha suppression by oral
      administration of lipoxygenase/cyclooxygenase inhibitors.
AB  - High fructose feeding causes diet-induced alterations of lipid metabolism and
      decreased insulin sensitivity, hallmark of which is a rapid and profound
      hypertriglyceridemia. One of the mechanisms that contribute to serum
      hypertriglyceridemia in this model is suppression of hepatic PPARalpha. HMG-CoA
      inhibitors, which reduce serum triglycerides in these animals, also
      elevate/restore hepatic PPARalpha. Previously we demonstrated that two known
      lipoxygenase/cyclooxygenase inhibitors reversed diet-induced hypertriglyceridemia
      in this model and that reversal of certain inflammatory markers in the liver
      correlated with the metabolic benefit. In this paper we extended these studies by
      examining the impact of these compounds on expression of PPARalpha, both at the
      level of transcription and expression. Our data show that diet-induced
      suppression of hepaic PPARalpha is reversed upon treatment with
      lipoxygenase/cyclooxygenase compounds. We then tested one of these compounds, BW
      755c, over a range of doses from 10 mg/kg to 100 mg/kg to establish a dose
      response relationship with the reduction of serum hypertriglyceridemia in this
      model. These experiments support the concept of using anti-inflammatory
      medications as one method to correct metabolic dysfunction.

PMID- 16091143
TI  - Phosphatidylserine treatment relieves the block to retrovirus infection of cells
      expressing glycosylated virus receptors.
AB  - BACKGROUND: A major determinant of retrovirus host range is the presence or
      absence of appropriate cell-surface receptors required for virus entry. Often
      orthologs of functional receptors are present in a wide range of species, but
      amino acid differences can render these receptors non-functional. In some cases
      amino acid differences result in additional N-linked glycosylation that blocks
      virus infection. The latter block to retrovirus infection can be overcome by
      treatment of cells with compounds such as tunicamycin, which prevent the addition
      of N-linked oligosaccharides. RESULTS: We have discovered that treatment of cells
      with liposomes composed of phosphatidylserine (PS) can also overcome the block to
      infection mediated by N-linked glycosylation. Importantly, this effect occurs
      without apparent change in the glycosylation state of the receptors for these
      viruses. This effect occurs with delayed kinetics compared to previous results
      showing enhancement of virus infection by PS treatment of cells expressing
      functional virus receptors. CONCLUSION: We have demonstrated that PS treatment
      can relieve the block to retrovirus infection of cells expressing retroviral
      receptors that have been rendered non-functional by glycosylation. These findings
      have important implications for the current model describing inhibition of virus
      entry by receptor glycosylation.

PMID- 16091144
TI  - Studies on Acanthocheilonema viteae cystatin: genomic organization, promoter
      studies and expression in Caenorhabditis elegans.
AB  - Cystatins are reversible, tightly binding inhibitors of cysteine proteases.
      Filarial cystatins have been ascribed immunomodulatory properties and have been
      implicated in protective immunity. To continue exploration of this potential,
      here we have determined the sequence, structure and genomic organization of the
      cystatin gene locus of A. viteae. The gene is composed of 4 exons separated by 3
      introns and spans approximately 2 kb of genomic DNA. The upstream genomic
      sequence contains transcriptional factor binding sites such as AP-1 and NF-Y, an
      inverted CCAAT sequence, and a TATA box. To investigate sites of cystatin
      expression, Caenorhabditis elegans worms were transformed by microinjection with
      the putative promoter region and the first exon of the A. viteae cystatin gene
      fused to the reporter GFP. In transgenic worms fluorescence was observed in the
      pharyngeal and rectal gland cells suggesting that cystatin is secreted.
      Additionally, A. viteae cystatin was expressed in C. elegans to explore its
      potential as an expression system for filarial genes.

PMID- 16091145
TI  - Ventriculo-atrial gradient due to first degree atrio-ventricular block: a case
      report.
AB  - BACKGROUND: Isolated, asymptomatic first degree AV block with narrow QRS has not
      prognostic significance and is not usually treated with pacemaker implantation.
      In some cases, yet, loss of AV synchrony because of a marked prolongation of the
      PR interval may cause important hemodynamic alterations, with subsequent symptoms
      of heart failure. Indeed, AV synchrony is crucial when atrial systole, the
      "atrial kick", contributes in a major way to left ventricular filling, as in case
      of reduced left ventricular compliance because of aging or concomitant structural
      heart disease. CASE PRESENTATION: We performed a trans-septal left atrium
      catheterization aimed at evaluating the entity of a mitral valve stenosis in a 72
      year-old woman with a marked first-degree AV block, a known moderate aortic
      stenosis and NYHA class III symptoms of functional deterioration. We occurred in
      a deep alteration in cardiac hemodynamics consisting in an end-diastolic
      ventriculo-atrial gradient without any evidence of mitral stenosis. The patient
      had a substantial improvement in echocardiographic parameters and in her symptoms
      of heart failure after permanent pacemaker implantation with physiological AV
      delay. CONCLUSION: We conclude that if a marked first degree AV block is
      associated to instrumental signs or symptoms of heart failure, the restoration of
      an optimal AV synchrony, achieved with dual-chamber pacing, may represent a
      reasonable therapeutic option leading to a consequent clinical improvement.

PMID- 16091146
TI  - Controlled, double-blind, randomized clinical trial to evaluate the impact of
      fruit juice consumption on the evolution of infants with acute diarrhea.
AB  - In order to assess the effects of juice feedings during acute diarrhea a double
      blind, randomized study was performed in 90 children, mean age of 10 +/- 4.28
      months. Thirty patients with acute diarrhea were fed twice-daily 15 ml/kg of
      Apple Juice (AJ), 30 received White Grape Juice (WGJ), and 30 were given colored
      and flavored water (WA) as part of their age appropriate dietary intake. The
      duration and severity of diarrhea were the main endpoint variables of the study
      performed in a metabolic unit. The patients were similar among the 3 groups, had
      diarrhea for 50-64 hours prior to admission, and were dehydrated when admitted to
      the unit for study. Half of the patients in each group were well nourished and
      the others had mild to moderate degrees of malnutrition. Rotavirus infection was
      the agent causing the illness in 63% of the patients. The infants fed juice
      ingested 14-17% more calories than those given WA, (those receiving AJ and WGJ
      ingested 95 and 98 Calories/Kg/d respectively) whereas those receiving WA
      consumed 81 cal/kg/d). The increased energy intake was not at the expense of
      other foods or milk formula. The mean body weight gain was greater among patients
      receiving WGJ (+ 50.7 gm) as compared with the patients in the AJ group (+ 18.3
      gm) or the patients fed WA (- 0.7 gm) (p = 0.08). The duration of the illness was
      longer in the infants fed juice as compared with those given WA (p = 0.006), the
      mean +/- SD duration in hours was 49.4 +/- 32.6, 47.5 +/- 38.9 and 26.5 +/- 27.4
      in patients fed AJ, WGJ and WA respectively. All patients improved while
      ingesting juice and none of them developed persistent diarrhea; most recovered
      within 50 hours of the beginning of treatment and less than one fourth had
      diarrhea longer than 96 hours in the unit. The fecal losses were also increased
      among the juice fed patients (p = 0.001); the mean +/- SD fecal excretion in
      g/kg/h was 3.94 +/- 2.35, 3.59 +/- 2.35, and 2.19 +/- 1.63 in AJ, WGJ and WA
      respectively. The stool output was highest during the first day of treatment
      among all the patients, though those fed AJ had the highest volume of fecal
      losses and those who received WA had the lowest stool excretion. After the first
      day of treatment the differences in fecal excretion were not significant. The
      ability to tolerate carbohydrates during the illness and immediately after
      recovery was similar among the 3 groups of patients. Intake of juices with
      different fructose/glucose ratios and osmolarities resulted in more fecal losses
      and more prolonged diarrhea as compared with water feedings, but the patients
      given juice ingested more calories and gained more weight, particularly among
      those being fed the juice with equimolar concentrations of fructose and glucose.

PMID- 16091147
TI  - DynGO: a tool for visualizing and mining of Gene Ontology and its associations.
AB  - BACKGROUND: A large volume of data and information about genes and gene products
      has been stored in various molecular biology databases. A major challenge for
      knowledge discovery using these databases is to identify related genes and gene
      products in disparate databases. The development of Gene Ontology (GO) as a
      common vocabulary for annotation allows integrated queries across multiple
      databases and identification of semantically related genes and gene products
      (i.e., genes and gene products that have similar GO annotations). Meanwhile,
      dozens of tools have been developed for browsing, mining or editing GO terms,
      their hierarchical relationships, or their "associated" genes and gene products
      (i.e., genes and gene products annotated with GO terms). Tools that allow users
      to directly search and inspect relations among all GO terms and their associated
      genes and gene products from multiple databases are needed. RESULTS: We present a
      standalone package called DynGO, which provides several advanced functionalities
      in addition to the standard browsing capability of the official GO browsing tool
      (AmiGO). DynGO allows users to conduct batch retrieval of GO annotations for a
      list of genes and gene products, and semantic retrieval of genes and gene
      products sharing similar GO annotations. The result are shown in an association
      tree organized according to GO hierarchies and supported with many dynamic
      display options such as sorting tree nodes or changing orientation of the tree.
      For GO curators and frequent GO users, DynGO provides fast and convenient access
      to GO annotation data. DynGO is generally applicable to any data set where the
      records are annotated with GO terms, as illustrated by two examples. CONCLUSION:
      We have presented a standalone package DynGO that provides functionalities to
      search and browse GO and its association databases as well as several additional
      functions such as batch retrieval and semantic retrieval. The complete
      documentation and software are freely available for download from the website
      http://biocreative.ifsm.umbc.edu/dyngo.

PMID- 16091148
TI  - Beta-adrenergic receptor activation in immortalized human urothelial cells
      stimulates inflammatory responses by PKA-independent mechanisms.
AB  - BACKGROUND: Interstitial cystitis (IC) is a debilitating disease characterized by
      chronic inflammation of the urinary bladder, yet specific cellular mechanisms of
      inflammation in IC are largely unknown. Multiple lines of evidence suggest that
      beta-adrenergic receptor (AR) signaling is increased in the inflamed urothelium,
      however the precise effects of these urothelial cell signals have not been
      studied. In order to better elucidate the AR signaling mechanisms of inflammation
      associated with IC, we have examined the effects of beta-AR stimulation in an
      immortalized human urothelial cell line (UROtsa). For these studies, UROtsa cells
      were treated with effective concentrations of the selective beta-AR agonist
      isoproterenol, in the absence or presence of selective inhibitors of protein
      kinase A (PKA). Cell lysates were analyzed by radioimmunoassay for generation of
      cAMP or by Western blotting for induction of protein products associated with
      inflammatory responses. RESULTS: Radioligand binding demonstrated the presence of
      beta-ARs on human urothelial UROtsa cell membranes. Stimulating UROtsa cells with
      isoproterenol led to concentration-dependent increases of cAMP production that
      could be inhibited by pretreatment with a blocking concentration of the selective
      beta-AR antagonist propranolol. In addition, isoproterenol activation of these
      same cells led to significant increases in the amount of phosphorylated
      extracellular signal-regulated kinase (pERK), inducible nitric oxide synthase
      (iNOS) and the induced form of cyclooxygenase (COX-2) when compared to control.
      Moreover, preincubation of UROtsa cells with the selective PKA inhibitors H-89 or
      Rp-cAMPs did not diminish this isoproterenol mediated phosphorylation of ERK or
      production of iNOS and COX-2. CONCLUSION: Functional beta-ARs expressed on human
      urothelial UROtsa cell membranes increase the generation of cAMP and production
      of protein products associated with inflammation when activated by the selective
      beta-AR agonist isoproterenol. However, the increased production of iNOS and COX
      2 by isoproterenol is not blocked when UROtsa cells are preincubated with
      inhibitors of PKA. Therefore, UROtsa cell beta-AR activation significantly
      increases the amount of iNOS and COX-2 produced by a PKA-independent mechanism.
      Consequently, this immortalized human urothelial cell line can be useful in
      characterizing potential AR signaling mechanisms associated with chronic
      inflammatory diseases of the bladder.

PMID- 16091149
TI  - Bystander effects in UV-induced genomic instability: antioxidants inhibit delayed
      mutagenesis induced by ultraviolet A and B radiation.
AB  - BACKGROUND: Genomic instability is characteristic of many types of human cancer.
      Recently, we reported that ultraviolet radiation induced elevated mutation rates
      and chromosomal instability for many cell generations after ultraviolet
      irradiation. The increased mutation rates of unstable cells may allow them to
      accumulate aberrations that subsequently lead to cancer. Ultraviolet A radiation,
      which primarily acts by oxidative stress, and ultraviolet B radiation, which
      initially acts by absorption in DNA and direct damage to DNA, both produced
      genomically unstable cell clones. In this study, we have determined the effect of
      antioxidants on induction of delayed mutations by ultraviolet radiation. Delayed
      mutations are indicative of genomic instability. METHODS: Delayed mutations in
      the hypoxanthine phosphoribosyl transferase (hprt) gene were detected by
      incubating the cells in medium selectively killing hprt mutants for 8 days after
      irradiation, followed by a 5 day period in normal medium before determining
      mutation frequencies. RESULTS: The UVB-induced delayed hprt mutations were
      strongly inhibited by the antioxidants catalase, reduced glutathione and
      superoxide dismutase, while only reduced glutathione had a significant effect on
      UVA-induced delayed mutations. Treatment with antioxidants had only minor effects
      on early mutation frequencies, except that reduced glutathione decreased the UVB
      induced early mutation frequency by 24%. Incubation with reduced glutathione was
      shown to significantly increase the intracellular amount of reduced glutathione.
      CONCLUSION: The strong effects of these antioxidants indicate that genomic
      instability, which is induced by the fundamentally different ultraviolet A and
      ultraviolet B radiation, is mediated by reactive oxygen species, including
      hydrogen peroxide and downstream products. However, cells take up neither
      catalase nor SOD, while incubation with glutathione resulted in increased
      intracellular levels of glutathione. Previously, we have shown that ultraviolet
      induced delayed mutations may be induced via a bystander effect and that this
      effect is 5-fold higher for UVB radiation than for UVA radiation. Therefore, we
      propose that the antioxidants inhibit an ultraviolet radiation-induced bystander
      effect and that the effect is transmitted via the medium and via an internal
      transfer between cells, like gap junctional intercellular communication, for UVB
      radiation and only by the latter mechanism for UVA radiation.

PMID- 16091150
TI  - Characterization of the linkage disequilibrium structure and identification of
      tagging-SNPs in five DNA repair genes.
AB  - BACKGROUND: Characterization of the linkage disequilibrium (LD) structure of
      candidate genes is the basis for an effective association study of complex
      diseases such as cancer. In this study, we report the LD and haplotype
      architecture and tagging-single nucleotide polymorphisms (tSNPs) for five DNA
      repair genes: ATM, MRE11A, XRCC4, NBS1 and RAD50. METHODS: The genes ATM, MRE11A,
      and XRCC4 were characterized using a panel of 94 unrelated female subjects (47
      breast cancer cases, 47 controls) obtained from high-risk breast cancer families.
      A similar LD structure and tSNP analysis was performed for NBS1 and RAD50, using
      publicly available genotyping data. We studied a total of 61 SNPs at an average
      marker density of 10 kb. Using a matrix decomposition algorithm, based on
      principal component analysis, we captured >90% of the intragenetic variation for
      each gene. RESULTS: Our results revealed that three of the five genes did not
      conform to a haplotype block structure (MRE11A, RAD50 and XRCC4). Instead, the
      data fit a more flexible LD group paradigm, where SNPs in high LD are not
      required to be contiguous. Traditional haplotype blocks assume recombination is
      the only dynamic at work. For ATM, MRE11A and XRCC4 we repeated the analysis in
      cases and controls separately to determine whether LD structure was consistent
      across breast cancer cases and controls. No substantial difference in LD
      structures was found. CONCLUSION: This study suggests that appropriate SNP
      selection for an association study involving candidate genes should allow for
      both mutation and recombination, which shape the population-level genomic
      structure. Furthermore, LD structure characterization in either breast cancer
      cases or controls appears to be sufficient for future cancer studies utilizing
      these genes.

PMID- 16091151
TI  - Arabidopsis ETO1 specifically interacts with and negatively regulates type 2 1
      aminocyclopropane-1-carboxylate synthases.
AB  - BACKGROUND: In Arabidopsis, ETO1 (ETHYLENE-OVERPRODUCER1) is a negative regulator
      of ethylene evolution by interacting with AtACS5, an isoform of the rate-limiting
      enzyme, 1-aminocyclopropane-1-carboxylate synthases (ACC synthase or ACS), in
      ethylene biosynthetic pathway. ETO1 directly inhibits the enzymatic activity of
      AtACS5. In addition, a specific interaction between ETO1 and AtCUL3, a
      constituent of a new type of E3 ubiquitin ligase complex, suggests the molecular
      mechanism in promoting AtACS5 degradation by the proteasome-dependent pathway.
      Because orthologous sequences to ETO1 are found in many plant species including
      tomato, we transformed tomato with Arabidopsis ETO1 to evaluate its ability to
      suppress ethylene production in tomato fruits. RESULTS: Transgenic tomato lines
      that overexpress Arabidopsis ETO1 (ETO1-OE) did not show a significant delay of
      fruit ripening. So, we performed yeast two-hybrid assays to investigate potential
      heterologous interaction between ETO1 and three isozymes of ACC synthases from
      tomato. In the yeast two-hybrid system, ETO1 interacts with LE-ACS3 as well as
      AtACS5 but not with LE-ACS2 or LE-ACS4, two major isozymes whose gene expression
      is induced markedly in ripening fruits. According to the classification of ACC
      synthases, which is based on the C-terminal amino acid sequences, both LE-ACS3
      and AtACS5 are categorized as type 2 isozymes and possess a consensus C-terminal
      sequence. In contrast, LE-ACS2 and LE-ACS4 are type 1 and type 3 isozymes,
      respectively, both of which do not possess this specific C-terminal sequence.
      Yeast two-hybrid analysis using chimeric constructs between LE-ACS2 and LE-ACS3
      revealed that the type-2-ACS-specific C-terminal tail is required for interaction
      with ETO1. When treated with auxin to induce LE-ACS3, seedlings of ETO1-OE
      produced less ethylene than the wild type, despite comparable expression of the
      LE-ACS3 gene in the wild type. CONCLUSION: These results suggest that ETO1 family
      proteins specifically interact with and negatively regulate type 2 ACC synthases.
      Our data also show that Arabidopsis ETO1 can regulate type 2 ACS in a
      heterologous plant, tomato.

PMID- 16091153
TI  - [How to win the battle against a shortage of tissues and organs for transplants?
      Expand the donor pool].

PMID- 16091152
TI  - Cross genome phylogenetic analysis of human and Drosophila G protein-coupled
      receptors: application to functional annotation of orphan receptors.
AB  - BACKGROUND: The cell-membrane G-protein coupled receptors (GPCRs) are one of the
      largest known superfamilies and are the main focus of intense pharmaceutical
      research due to their key role in cell physiology and disease. A large number of
      putative GPCRs are 'orphans' with no identified natural ligands. The first step
      in understanding the function of orphan GPCRs is to identify their ligands.
      Phylogenetic clustering methods were used to elucidate the chemical nature of
      receptor ligands, which led to the identification of natural ligands for many
      orphan receptors. We have clustered human and Drosophila receptors with known
      ligands and orphans through cross genome phylogenetic analysis and hypothesized
      higher relationship of co-clustered members that would ease ligand
      identification, as related receptors share ligands with similar structure or
      class. RESULTS: Cross-genome phylogenetic analyses were performed to identify
      eight major groups of GPCRs dividing them into 32 clusters of 371 human and 113
      Drosophila proteins (excluding olfactory, taste and gustatory receptors) and
      reveal unexpected levels of evolutionary conservation across human and Drosophila
      GPCRs. We also observe that members of human chemokine receptors, involved in
      immune response, and most of nucleotide-lipid receptors (except opsins) do not
      have counterparts in Drosophila. Similarly, a group of Drosophila GPCRs
      (methuselah receptors), associated in aging, is not present in humans.
      CONCLUSION: Our analysis suggests ligand class association to 52 unknown
      Drosophila receptors and 95 unknown human GPCRs. A higher level of phylogenetic
      organization was revealed in which clusters with common domain architecture or
      cellular localization or ligand structure or chemistry or a shared function are
      evident across human and Drosophila genomes. Such analyses will prove valuable
      for identifying the natural ligands of Drosophila and human orphan receptors that
      can lead to a better understanding of physiological and pathological roles of
      these receptors.

PMID- 16091154
TI  - [Paradoxical cortical response during the intermittent photo stimulation in the
      dissociated strabismus].
AB  - OBJECTIVES: To determine the behavior of the visual cerebral cortex during the
      photo stimulation in the dissociated strabismus. MATERIAL AND METHODS: We
      elaborated a digital cerebral mapping using the international 10-20 system with
      21 electrodes and an option of a register of 32 channels with established
      parameters in every period (printed and with pulse monitoring) applied to two
      children with dissociated strabismus. We registered and evaluated the cortical
      response to different stimuli: luminous, hyperventilation, closing and opening of
      eyelids, asleep and awake; through digital electroencephalography, as well as the
      registering of ocular movements with electroculography and video film with
      infrared light. RESULTS: We discovered a paradoxical neuroelectrical response and
      the visual cerebral cortex during the intermittent photo stimulation never
      reported before, showing the neuroelectrical changes that occur in the
      dissociated horizontal deviation (DHD). We correlated these findings with the
      origin of the dissociated strabismus.

PMID- 16091155
TI  - [Profile of maxillofacial trauma in bicycle accidents].
AB  - OBJECTIVE: To determine the maxillofacial trauma profile, concomitant results and
      treatment of those persons injured in bicycle accidents. Several variables were
      identified such as age, sex, mechanism, place, month, injury patterns and
      symptomatology, time for receiving medical care, and treatments. MATERIAL AND
      METHODS: This was an exploratory, descriptive, analytic, and retrospective study.
      All patients with maxillofacial trauma injury as a result of bicycle accidents
      were admitted to the emergency service in 2002 in the traumatology hospital
      Victorio de la Fuente Narvaez, Mexican Institute of Social Security that covers
      the entire Federal District zone and some suburbs, without any distinction made
      as to injury specialty. RESULTS: Patients (127) with maxillofacial trauma from
      bicycle accidents were identified. Children aged 6 to 10 years were the most
      affected. There was more injury in soft tissue in the midfacial area, such as
      contusions, injuries dermabrasion and some fractures resulting in nose trauma.
      Most of the accidents happened in the streets by falling from the bicycles. Forty
      six persons had more than two maxillofacial injuries. Head trauma with cervically
      projected sprain was demonstrated as associated trauma. More than 50% of the
      patients received immediate treatment under local anesthesia by maxillofacial
      surgery or orthopedics and traumatology during the afternoon and night.
      CONCLUSIONS: Prevention programs for parents and children in homes, schools and
      medical care facilities should be established to encourage traffic education and
      the use of protective headgear.

PMID- 16091156
TI  - [Relaparotomy on demand: factors related to mortality].
AB  - OBJECTIVE: To assess the mortality related factors of patients after relaparotomy
      on demand. BACKGROUND: In some patients, a relaparotomy after a primary
      laparotomy will be necessary, most due to acute complications. The relaparotomy
      can be planned or on demand based on the evolution of the patient. Which of these
      approaches is better is still a matter of debate. MATERIAL AND METHODS: Thirty
      three patients underwent relaparatomy on demand in a general surgery unit.
      RESULTS: Of 51 relaparotomies, 98% were positive. Nineteen of the 33 patients
      died, resulting in a mortality rate of 58%. The factors associated with mortality
      were development of an intestinal fistula (p < 0.02), wound infection (p < 0.03),
      generalized peritonitis in the primary surgery (p < 0.001), urgent primary
      laparotomy (p < 0.003), development of multiple organ failure (p < 0.005), and
      respiratory insufficiency (p < 0.01). CONCLUSIONS: Laparotomy on demand is useful
      in the treatment of patients with abdominal sepsis; however, the mortality is
      still very high.

PMID- 16091157
TI  - [Early diagnosis and risk factors associated with abdominal compartment
      syndrome].
AB  - INTRODUCTION: Abdominal compartment syndrome (ACS) is a clinical entity that
      develops after sustained and uncontrolled intraabdominal hypertension (IAHT). The
      ACS is clinically characterized by a massively distended abdomen and respiratory,
      cardiovascular, neurologic, and renal dysfunction. OBJECTIVE: The goal of this
      study was to demonstrate the benefit of early diagnosis of intra-abdominal
      hypertension and ACS and to identify risk factors associated with mortality.
      MATERIAL AND METHODS: We used a prospective study that included all patients
      admitted to Hospital de Especialidades Miguel Hidalgo with known ACS risk factors
      between January 2002 and December 2003. All patients were submitted to systematic
      measurements of intra-abdominal pressure (IAP). Those patients with grade III-IV
      IAHT were treated with decompressive laparotomy. RESULTS: Included in the study
      were 32 patients (23 males and 9 females). Mean age was 45.0 +/- 18.34 years.
      Twenty three patients developed IAHT grade I-II (group I) and nine developed
      grade IIIIV (group II). All group II patients were treated with abdominal
      decompression. The most common clinical entities associated were closed abdominal
      trauma (28%), hernias (15%), intestinal occlusions: (12.5%), acute pancreatitis
      (9.4%) and mesenteric ischemia (6.3%). Grade III-IV IAHT was statistically
      associated with reoperation (p = 0.038), acidosis (p = 0.003), anuria (p < 0.001)
      and sustained arterial hypotension (p = 0.004). The significant variables
      associated to mortality were anuria (p = 0.024) and grade III-IV IAHTA (0.017).
      CONCLUSIONS: It is possible to make an early diagnosis of IAHT and ACS with an
      indirect measurement of IAP. The most important factors related to mortality are
      anuria and IAHT.

PMID- 16091158
TI  - [Restorative proctocolectomy with J-pouch reservoir. Experience in a national
      medical center].
AB  - OBJECTIVE: To present the experience for morbidity and mortality of surgical
      treatment of chronic ulcerative colitis (CUC) and familiar adenomatous polyposis
      (FAP) with restorative proctocolectomy with J-pouch. MATERIAL AND METHODS: We
      used a cases series of patients treated consecutively from January 1993 to
      December 2003. Selection criteria were patients with J-pouch restorative
      proctocolectomy with CUC and FAP who were treated and assessed prospectively.
      RESULTS: There were 16 cases treated with restorative proctocolectomy (nine males
      and seven females). Diagnosis of inflammatory bowel disease was established in 12
      patients, and 4 with familiar adenomatous polyposis. Age average was 33 years.
      All cases had protective ileostomy. Seven patients developed at least one
      complication such as pelvic abscess, uretheral transection, pulmonary
      thromboembolism, hemoperitoneum, persistent transrectal bleeding, wound infection
      and sexual impotence. Only four patients required surgical reintervention. The
      median hospital stay was 11.9 days. Average bowel movements at 3 month-follow-up
      was 10.1, at 6 months 6.6. Medium average follow-up was 44.25 months. There was
      no mortality. CONCLUSIONS: Results of this study demonstrated adequate quality of
      life and appropriate functional results; rate of morbidity was acceptable with no
      mortality.independent of morbidity there was no mortality. Long-term follow up is
      necessary to identify long-term-late complications.

PMID- 16091159
TI  - [Experiences with the en bloc multiorgan procurement technique].
AB  - INTRODUCTION: The pressing need to obtain organs for transplantation demands an
      optimal usage of donors. Surgical techniques based on rapid multiorganic
      retrieval gain vital importance especially when hemodynamically unstable donors
      are involved. OBJECTIVE: To highlight the advantages of this technique and
      evaluate our experience after 2 years of implementation. MATERIAL AND METHODS: A
      longitudinal, prospective non-controlled study was performed, including 34
      multiorganic retrievals using the Total Abdominal Evisceration (TAE) technique.
      Information on demographic characteristics, surgical times, anatomical variations
      and final fate of organs is gathered. RESULTS: Thirty four organ retrievals were
      performed using TAE techniques. Included donors had a mean age of 47 years and a
      mean weight of 66 kg. Dissection time range was 35 +/- 10 min, bloc retrieval was
      performed in 20 +/- 8 min and dissection at backbench range was 100 +/- 30 min.
      All anatomic variations were detected and were present in 46.9% of cases. Over
      70% of livers retrieved by TAE resulted in minimal preservation injury. Only one
      presented primary non-function after transplantation, directly related to
      hemodynamic instability. CONCLUSIONS: The TAE technique for multiorgan retrieval
      allows adequate harvesting of organs for transplantation with favorable
      preservation. It is a valid alternative for transplant groups in our country,
      especially when dealing with unstable donors.

PMID- 16091160
TI  - [Defensive medicine in Mexico: an explorative survey of its characteristics].
AB  - INTRODUCTION: defensive medicine, has been recognized as a problem for health
      services in several countries of the world. It is defined as the application of
      treatments, tests and procedures with the main intention to defend the doctor of
      critic's and to avoid controversies, regarding diagnosis or patient's treatment.
      There are multiple causes of the defensive medicine: the fundamental is patient
      doctor relationship without the necessary trust. MATERIAL AND METHODS: the
      present reports it is a observational, cross-sectional and descriptive study of
      exploratory nature, with the objective to consider the dimension of the defensive
      medicine (MD) in Mexico. A survey was designed to pilot an application with
      Likert scale in a representative sample. 613 doctors participated to national
      level, with index of confidence of 95% and maximum error of 5% (p < 0.05). The
      questions explore the level in agreement or disagreement with perceptions,
      specific attitudes and conducts that are related to the MD practice. RESULTS:
      categories and degrees in the defensive practices of the interviewed doctors
      settled down, 38,7% were nondefensive, whereas 61,3% presented association with
      some MD degree (p < 0.05). CONCLUSIONS: The defensive attitude of the participant
      doctors is high, it emphasizes the importance of establishing measures that
      stimulate their containment and fights, which will allow to improve the quality
      of the medical practice and the doctor-patient relationship. The instrument
      maintained a degree of confidence and sensitivity (p < 0.05), that its future use
      allows.

PMID- 16091161
TI  - Iatrogenic dissection of the right coronary artery and the ascending aorta
      secondary to endoluminal angioplasty. A case report.
AB  - The authors present the case of a 54-year-old woman with iatrogenic dissection of
      the right coronary artery ostium and extension of the dissection to the ascending
      aorta during the intraluminal angioplasty of an obstructive lesion in the middle
      portion of the right coronary artery. In order to maintain coronary blood flow
      before surgery, the coronary dissection was treated with the implantation of
      three direct coronary stents that dilated the stenosis and sealed the dissection
      of the coronary artery. The aortic dissection needed treatment with the
      implantation of a Haenoshield aortic graft. During the surgery, it was decided to
      implant an aortocoronary bypass graft to guarantee the distal right coronary
      blood flow, given the possible increased risk of thrombosis of the stents because
      of the large thrombogenic metallic surface of the stents. On the other hand, the
      administration of anticoagulants and antithrombotic drugs were not indicated
      because of the intended surgery of the aortic dissection. The evolution of the
      patient was satisfactory. Causes, frequency, and treatment procedures of this
      iatrogeny are discussed.

PMID- 16091162
TI  - [Cadaveric kidney transplant using horseshoe kidney: report of two cases].
AB  - The number of patients awaiting a renal transplant is increasing. The shortage of
      organs demands the exploration of alternative organ sources such as kidneys with
      congenital anatomical anomalies. The horseshoe kidney is the most common renal
      anatomical anomaly and is able to be transplanted en bloc or split after
      procurement with good results. The decision whether to divide a horseshoe kidney
      depends on several factors. The most important feature is the number and position
      of the renal vessels. The second is the collector system anatomy. In this study
      we present two technically successful cases of renal transplantation using
      horseshoe kidneys en bloc with good results. Both cases have normal renal
      function. Horseshoe kidney transplantation offers good results and therefore
      should be considered as an option for cadaver kidney transplantation.

PMID- 16091163
TI  - [Maffucci's syndrome. Case reports and literature review].
AB  - Maffucci syndrome is a rare, congenital disease, which is associated with the
      appearance of multiple enchondromas (possibility of malignant transformation in
      20 to 100%), soft tissue hemangiomas and other mesenchymatous injuries. Case 1 is
      a 33-year-old female who presented with multiple nodules predominantly in upper
      extremities. Upon examination, there was deformity in articulation and nodules on
      the hands, which were soft and moveable. There were bony shavings in the second
      and fourth fingers of the left hand (enchondromas and atypical cells associated
      with hemangioma esclerosante). Maffucci syndrome was diagnosed. Later, excision
      of subcutaneous nodules in superior extremities was performed along with excision
      of nodules in both hands and hypochondrium (enchondroma injuries of left hand and
      hypochondrium, hemangioma in right hand). There was dysarticulation of the second
      finger at the metacarpal level of the phalanges of the left hand
      (chondrosarcoma). The patient is being followed up currently. Case 2 is a 26-year
      old female. The patient had a history of subcutaneous abdominal tumor, exostosis,
      nodules and nodule in right breast. Upon examination, a tumor was found in the
      right breast, exostosis of right tibia, injury to the right wrist and left
      thyroid nodule. A simple mastectomy and axillary dissection was performed
      (fibroadenoma to intracanalicular and 14 negative lymph nodes). Later, left
      thyroidectomy and lumpectomy in right wrist were performed (hyperplasia to
      nodular thyroid and hemangioma cavernous). There was injury in the carpus of the
      right hand and elbow (hemangioma cavernous and synovial tissue with fibrosis and
      enchondroma). A diagnosis was made of Marffucci syndrome associated with
      mesenchymatous tumors. The patient was in poor general health and did not survive
      this hospitalization.

PMID- 16091164
TI  - [Practice guidelines for the management of acute perioperative pain].
AB  - The inadequacy of perioperative management causes a severe adverse outcome, a
      prolonged time of hospitalization and unnecessary suffering. Therefore, it is
      important to provide an effective management approach to the patient with
      perioperative pain. A task force with experience in this field systematically
      develops practice guidelines and the primary goal is to facilitate, to health
      care professionals, decision-making regarding pain relief. The well-known concept
      of "administer as needed" is inaccurate and must be eliminated from hospital's
      management protocols in order to facilitate the staff education to decrease the
      painful experience. A method to evaluate and document pain in an objective and
      periodic way shall be implemented. Also, analgesic therapy shall be
      individualized and chosen regarding pain intensity in every surgical procedure.
      The treatment options include the use of non-opiate and opiate drugs, regional
      analgesia and nonpharmacological techniques. The best analgesic will be the one
      that shall provide the highest relief of pain with the fewest side effects. In
      the pediatric and obstetric populations, special considerations for the
      ambulatory patient must be taken. Finally, these practice guidelines could be the
      reference for future practice guidelines on pain management in Mexico.

PMID- 16091165
TI  - [Discussion about vaccines from animal origin at the Mexican National Academy of
      Medicine in the XIX century].
AB  - This is a recount about the prevailing ideas in Mexico during the second half of
      the XIX century for introducing the use of vaccines of animal origin; thus, the
      thoughts of men like Agustin Andrade, Angel Iglesias y Dominguez, Lino Ramirez,
      Fernando Malanco and Luis E. Ruiz, who emphasized this work.

PMID- 16091166
TI  - [Brief history of hospital care in Tapachula, Chiapas, Mexico].
AB  - This paper presents the history of hospital care in Tapachula, Chiapas. Hospital
      services began 100 years ago. At present there is one government hospital,
      hospitals of the Social Security systems, private hospitals and one hospital of
      the Mexican Red Cross. Hospital services have been oriented to attend labor and
      delivery, infectious diseases, malnutrition and accidents.

PMID- 16091167
TI  - [Dances of the day of the dead. From suicide tendency to fear of death].

PMID- 16091168
TI  - [Factors related to the olive size in patients with hypertrophic pyloric
      stenosis].

PMID- 16091170
TI  - [Clinicopathologic study of 369 B-cell non-Hodgkin lymphoma cases, with reference
      to the 2001 World Health Organization classification of lymphoid neoplasms].
AB  - OBJECTIVE: To describe the relative frequency, morphologic features,
      immunophenotype and clinical data of different types of B-cell non-Hodgkin
      lymphoma (B-NHL) and to evaluate the practical application of the 2001 World
      Health Organization (WHO) classification of lymphoid neoplasms. METHODS: 369
      documented cases of B-NHL were further subtyped according to the 2001 WHO
      classification of lymphoid neoplasms, on the basis of hematoxylin and eosin
      staining, immunohistochemistry and in-situ hybridization techniques. RESULTS:
      Amongst the 369 cases of B-NHL studied, 353 cases could be further classified
      into 11 subtypes. Diffuse large B-cell lymphoma, extranodal marginal zone
      lymphoma and follicular lymphoma were the commonest subtypes, accounting for
      51.2% (189 cases), 14.9% (55 cases) and 10.6% (39 cases) of all cases
      respectively. Tumors in lymph nodes were seen in 158 cases (42.8%) and in extra
      node in 211 cases (57.2%). B-cell prolymphocytic leukemia and hairy cell leukemia
      were not identified. When comparing the diagnosis based on morphologic
      examination alone with the diagnosis based on both morphology and
      immunophenotype, there was a 80% concordance rate. Immunohistochemical study was
      helpful in reaching the correct diagnosis in many cases and could improve the
      overall diagnostic accuracy by about 20%. CONCLUSIONS: Amongst cases of B-NHL,
      diffuse large B-cell lymphoma is the commonest subtype, followed by MALToma and
      follicular lymphoma. While morphologic examination forms the basis for lymphoma
      diagnosis, immunohistochemical study also plays an important role in further
      subtyping. A combination of both modalities are sufficient for arriving at an
      accurate diagnosis in most cases of B-NHL, in keeping with the recommendation of
      the 2001 WHO classification of lymphoid neoplasms.

PMID- 16091171
TI  - [Sensitivity and specificity of granzyme B and perforin in diagnosing acute
      rejection after liver transplantation].
AB  - OBJECTIVE: To study the roles of granzyme B and perforin in diagnosing acute
      rejection after liver transplantation, and the relationship between their
      activity index (AI) and Banff's histological grading criteria. METHODS: Liver
      biopsies were processed as for routine surgical specimens and labeled with
      granzyme B and perforin monoclonal antibodies. The number of positive cells/mm(2)
      was determined as activity index (AI) by IPP image analysis software. Histologic
      findings were used as the "gold standard" in diagnosing acute rejection. RESULTS:
      Of 41 liver biopsy samples studied, acute rejection was noted in 21 cases, the
      remaining 20 cases showed no evidence of rejection. The AI of granzyme B and
      perforin in the acute rejection group was significantly higher than that in the
      non-acute rejection group (< 0.001). In the acute rejection group, the AI in
      moderate to severe acute rejection was higher than that in mild to indeterminate
      acute rejection (< 0.001). Compared with the "golden" histologic criteria, the
      sensitivity, specificity, positive predictive value, negative predictive value
      and accuracy of granzyme B in diagnosing acute rejection were 90.0%, 95.2%,
      94.7%, 90.9% and 92.7% respectively. The values of these parameters for perforin
      were also above 80%. CONCLUSIONS: Granzyme B and perforin are key markers of
      activated immune cells in acute rejection and highly expressed during acute liver
      rejection episodes. As ancillary investigations, these parameters demonstrated
      high sensitivity and specificity in diagnosing acute rejection in allograft post
      transplant liver biopsies.

PMID- 16091172
TI  - [Expression of NY-ESO-1 and LAGE-1 cancer-testis antigens in hepatocellular
      carcinoma].
AB  - OBJECTIVE: To study the role of NY-ESO-1 and LAGE-1 cancer-testis antigens as
      targets for immunotherapy and the relationship between corresponding gene
      expression and biologic behavior of hepatocellular carcinoma (HCC). METHODS: The
      expression of NY-ESO-1 and LAGE-1 was studied in frozen tumor tissues from 30
      cases of HCC by reverse transcriptase-polymerase chain reaction and
      immunohistochemistry. NY-ESO-1 expression and its distribution were further
      studied by immunohistochemistry in a tissue array contained 191 cases of HCC.
      RESULTS: NY-ESO-1 and LAGE-1 mRNAs were expressed in 33.3% (10/30) and 16.7%
      (5/30) of HCC respectively. Either NY-ESO-1 or LAGE-1 was expressed in 36.7%
      (11/30) cases. NY-ESO-1 was expressed mainly in the cytoplasm of tumor cells. It
      was positive in 13.8% (24/174) cases of HCC. There was an increased expression of
      NY-ESO-1 from 6.8%, 3/44 in small HCC, 16.2%, 21/130 in advanced HCC and 23.1%,
      12/52 in metastatic HCC. The expression in the non-metastatic group was 9.8%
      (12/122). The differences between the metastatic group and non-metastatic group
      (< 0.05) and between normal liver tissue and HCC (< 0.01) were statistically
      significant. There was no relationship between NY-ESO-1 expression and tumor
      size. NY-ESO-1 and LAGE-1 were not detected in adjacent normal liver tissue.
      CONCLUSIONS: NY-ESO-1 and LAGE-1 are expressed in a high percentage of HCC,
      especially in cases with metastasis. It is thus possible that NY-ESO-1/LAGE-1 can
      serve as targets for antigen-specific immunotherapy in HCC and NY-ESO-1 peptide
      vaccination may be of use for patients with advanced HCC.

PMID- 16091173
TI  - [Expression of p120ctn and its significance in non-small cell lung cancer].
AB  - OBJECTIVE: To investigate the expression of p120(ctn) in non-small cell lung
      cancer (NSCLC) and its correlation with the clinical and pathologic parameters.
      METHODS: Immunohistochemistry (S-P method) was used to detect the expression of
      p120(ctn) in 143 NSCLC cases. The variation of protein expression was further
      analyzed in 36 cases by Western blot. The correlation with clinical and
      pathologic parameters was studied. RESULTS: Immunohistochemically, normal
      bronchial cells showed membranous expression for p120(ctn), while NSCLC was
      characterized by cytoplasmic or diminished membranous staining. The rate of
      abnormal p120(ctn) expression was 79.7% (114/143). There was a significant
      correlation between abnormal expression of p120(ctn) and tumor differentiation,
      clinical stage, lymph node metastasis and poor prognosis (< 0.05), but not
      histologic typing. Western blot showed that the total amount of p120(ctn) in
      normal bronchial cells was significantly higher than that in NSCLC. The p120(ctn)
      isoform 1 (120,000) and isoform 3 (100,000) were expressed in normal lung tissue,
      while there was a reduced expression or absence of isoform 1 in NSCLC.
      CONCLUSION: The expression of p120(ctn) is abnormal in NSCLC; p120(ctn) may serve
      as a useful prognostic marker for NSCLC.

PMID- 16091174
TI  - [Clinical and pathologic features of malignant myoepithelioma of salivary
      glands].
AB  - OBJECTIVE: To analyze the clinical features, morphology and biologic behavior of
      primary malignant myoepithelioma (MME) of salivary glands. METHODS: The H&E
      sections of 16 MME cases were reviewed. Immunohistochemical study using EnVision
      method for cytokeratin (CK), epithelial membrane antigen (EMA), vimentin, S-100
      protein, desmin, muscle-specific actin (MSA), smooth muscle actin (SMA), Myo,
      proliferation cell nuclear antigen (PCNA), leukocyte common antigen (LCA) and
      glial fibrillary acidic protein (GFAP) was carried out. RESULTS: Of the 16
      patients studied, 6 were males and 10 were females. Their ages ranged from 12 to
      65 years (with an average age of 44 years). The tumor occurred predominantly in
      the parotid gland and minor salivary gland of the palate. Common clinical
      features included sudden and rapid tumor growth, superficial ulceration, bony
      destruction and nerve infiltration. Seven of the 16 patients developed local
      recurrences, while 2 patients had metastasis in the lymph nodes of submandibular
      or other cervical regions. Most tumors infiltrated adjacent normal salivary
      gland, adipose, muscular and bony tissues. The extent of local invasion however
      varied. Histologically, MME showed a wide range of morphologic appearance, with
      various combinations of clear, spindle, epithelioid or plasmacytoid cells. The
      tumor cells were atypical and demonstrated high mitotic activity. In this study,
      9 cases were composed predominantly of clear tumor cells. Immunohistochemically
      the tumor cells were positive for CK, EMA, MSA, desmin and S-100 protein.
      CONCLUSIONS: In general, MME is a rare and low-grade malignant salivary gland
      tumor. It carries a low potential for lymph node or distant metastasis but
      relatively high tendency for local recurrences, resulting in destruction of
      adjacent soft and bony tissues. The biologic behavior also varies, depending on
      the site of involvement. Morphologic diagnosis of MME can be difficult in view of
      the wide spectrum of histologic changes. A definitive diagnosis however is
      possible with the application of immunohistochemistry.

PMID- 16091175
TI  - [Monoclonal antibody against G3BP: preparation, characterization and its
      application in analysis of human tumors].
AB  - OBJECTIVE: To better understand the molecular mechanism of tumorigenesis and
      progression, the monoclonal antibody against G3BP (Ras-GAP SH3 binding protein),
      which serves as an important downstream effector of Ras signaling, was prepared,
      characterized and utilized in analysis of various human tumors. METHODS: By using
      the prokaryotic expression vector pGEX-5X1, GST-G3BP fusion protein was expressed
      in E. coli BL21 under induction of IPTG. Purified GST-G3BP fusion protein was
      used to immunize BALB/c mice. The monoclonal antibody against G3BP was produced
      through conventional hybridoma method and characterized by ELISA, Western blot
      and immunohistochemical staining. RESULTS: A hybridoma cell line secreting anti
      G3BP IgG1 subtype antibody was obtained. Western blot and competitive inhibition
      assay showed that the antibody was G3BP-specific. Immunohistochemical staining
      demonstrated that G3BP was over-expressed in formalin-fixed and paraffin-embedded
      tissues of some human tumors, such as lung cancer, colon cancer, gastric cancer
      and breast cancer. In breast cancer specimens, the degree of G3BP expression
      correlated positively with the presence of lymph node metastasis and c-erbB2
      expression. CONCLUSIONS: The G3BP-specific monoclonal antibody derived from
      recombination protein can be used in ELISA, Western blot and immunohistochemical
      assay. It may provide an important tool in analysis of G3BP in in vitro and in
      vivo experiments. Besides, G3BP may serve as another prognostic marker for breast
      cancer.

PMID- 16091176
TI  - [Preliminary study on human embryonic kidney cell line HEK-293 after porcine
      endogenous retrovirus infection].
AB  - OBJECTIVE: To assess the infectivity of porcine endogenous retrovirus (PERV) via
      in vitro infection of human embryonic kidney cell line HEK-293. METHODS: PERV
      particles were detected by immunoelectron microscopy. PERV DNA and mRNA were
      studied in HEK-293 24 hours after the infection using polymerase chain reaction
      and reverse transcriptase-PCR respectively. The PERV types were also analyzed.
      PERV-gag protein was observed by confocal microscopy. RESULTS: Retroviral
      particles were round under electron microscope. PERV-gag pol gene and gag protein
      were detected and expressed in the infected HEK-293 cells. The types of PERV were
      PERV-A and PERV-B. PERV-gag protein was also identified in the cytoplasm of
      infected cells by confocal microscopy. CONCLUSIONS: PERV is able to infect HEK
      293 cell line in vitro; types of PERV-gag protein is also expressed as a result.
      Further studies are thus necessary in order to evaluate the possibility of
      xenozoonoses in pig-to-human xenotransplantation.

PMID- 16091177
TI  - [Suppressive effects of par-4 antisense oligodeoxynucleotide on up-regulation of
      intracellular calcium concentration in PC12 cell induced by glutamate and its
      anti-apoptosis effects].
AB  - OBJECTIVE: To investigate the uppressive effects of par-4 antisense
      oligodeoxynucleotide on the up-regulation of intracellular calcium concentration
      in PC12 cell induced by glutamate and its anti-apoptosis effects. METHODS:
      Cationic lipid-mediated par-4 antisense oligodeoxynucleotide (par-4-AS-ODN) was
      transfected into PC12 cells and followed by glutamate for treatment. Mismatch
      oligodeoxy-nucleotide (MS-ODN) was used as the control. Morphological assessment
      and evaluation of the anti-apoptosis effects of par-4-AS-ODN on PC12 cells were
      performed by laser scanning confocal microscopy by double staining of the cells
      with Hoechest 33258/propidium iodide (Hoe/PI) and flow cytometry respectively.
      The mRNA and protein levels of calpain 10 and par-4 were measured by RT-PCR and
      Western blot. Intracellular calcium concentration was determined by using laser
      scanning confocal microscope with Fura-2/AM as the fluorescent dye. RESULTS: Par
      4-AS-ODN repress the increase of par-4 protein in PC12 cell (52.3 +/- 5.0 vs 90.0
      +/- 3.2, < 0.01). Par-4-AS-ODN significantly inhibited the apoptosis of PC12
      cells induced by glutamate (53% vs 31%, < 0.01). Par-4-AS-ODN significantly
      suppress the up-regulation of intracellular calcium concentration in PC12 cells
      induced by glutamate (Rate of fluorescent density: 167.9 +/- 32.4 vs 228.8 +/-
      36.8, < 0.01). Par-4-AS-ODN inhibited the increase of calpain 10 mRNA in PC12
      cells induced by glutamate (46.3 +/- 3.7 vs 34.8 +/- 2.1, < 0.01). CONCLUSIONS:
      par-4-AS-ODN enables to inhibit apoptosis of PC12 cells induced by glutamate. The
      mechanism of the inhibition may be closely related to suppression of the up
      regulation of intracellular calcium concentration and calpain transcription
      expression.

PMID- 16091178
TI  - [Effect of wortmannin on endothelial cell proliferation and migration induced by
      high glucose Muller cell conditioned medium].
AB  - OBJECTIVE: To investigate the effect of wortmannin on endothelial cells
      proliferation and migration induced by high glucose Muller cell conditioned
      medium (HGMCM). METHODS: Immunofluorescence, flow cytometry and Boyden chamber
      migration models were used to analyze the effect of wortmannin on endothelial
      cells. RESULTS: 50 nmol/L wortmannin could significantly inhibit the
      proliferation and migration of endothelial cells induced by HGMCM. The percentage
      of endothelial cells in S phase was obviously decreased [from (37.82 +/- 0.57)%
      to (21.91 +/- 0.23)%, P < 0.01], while there was an increase in the percentage of
      cells in G(0)/G(1) phase [from (54.57 +/- 1.19)% to (65.59 +/- 0.41)%, < 0.01]
      and G(2)/M phase (< 0.05). CONCLUSION: Wortmannin can inhibit proliferation and
      migration of endothelial cells induced by HGMCM, suggesting that wortmannin
      carries an anti-angiogenetic ability in diseased retina.

PMID- 16091179
TI  - [Isolation, culture and identification of endothelial cells from rat glomeruli].

PMID- 16091180
TI  - [A clinicopathologic study of ten cases of cellular schwannoma].

PMID- 16091182
TI  - [Gleason grading of prostatic adenocarcinoma].

PMID- 16091181
TI  - [Advances of lymphoblastic lymphoma and its molecular genetics].

PMID- 16091183
TI  - [Triple staining of immunohistochemistry].

PMID- 16091184
TI  - [Congenital neurocutaneous melanosis].

PMID- 16091185
TI  - [Primary leydig cell tumor of epididymis: a case report].

PMID- 16091186
TI  - [Chondroid matrix-producing metaplastic carcinoma of the breast].

PMID- 16091187
TI  - [Colon hepatoid adenocarcinoma with live metastasis].

PMID- 16091188
TI  - [Pleomorphic adenoma of nasal cavity in fancy].

PMID- 16091189
TI  - [Clear cell sarcoma of temporal soft tissues: a case report].

PMID- 16091190
TI  - [Cementoblastoma: report of a case].

PMID- 16091191
TI  - The patient and Web-based cancer information: a role for provider input into this
      rapidly evolving relationship.

PMID- 16091192
TI  - Advances in the molecular genetics of acute leukemia.
AB  - Acute leukemias are characterized by the unrestrained clonal proliferation of
      hematopoietic precursor cells coupled with aberrant or arrested differentiation.
      The molecular basis of hematopoiesis and leukemogenesis is still being defined,
      yet it is increasingly evident that acute leukemias have recurrent molecular
      features that can be exploited for diagnostic, prognostic, and therapeutic
      purposes. Modern molecular technologies already influence treatment strategies
      for these diseases, and it is likely that as such technology matures it will have
      an increasing impact on all aspects of acute leukemia management. This article
      reviews recent developments in the molecular classification, prognostication, and
      treatment of the acute leukemias.

PMID- 16091193
TI  - Advances in the treatment of chronic lymphocytic leukemia.
AB  - A dramatic change has taken place in therapy for chronic lymphocytic leukemia
      over the past 15 years. In 1990, available therapy produced complete responses in
      less than 5% of treated patients. This is in marked contrast to modern regimens,
      which can reliably produce complete responses in over 50% of patients. This
      remarkable improvement is completely attributable to the introduction of new
      active agents. These new agents include three purine analogues (pentostatin,
      fludarabine, and cladribine) and two monoclonal antibodies (rituximab and
      alemtuzumab). Novel combinations of these agents have emerged as effective new
      therapies for previously untreated and pretreated patients. Clinical studies
      indicate that such combinations can induce higher response rates--including
      complete responses--than single-agent therapy. Those patients who achieve a
      complete response have superior survival, compared with those who only achieve a
      partial response. Though not yet demonstrated in a prospective randomized trial,
      treatment approaches aimed at achieving high-quality responses may one day lead
      to an improvement in survival for patients with chronic lymphocytic leukemia and,
      ultimately, offer the hope of curative therapy in these patients.

PMID- 16091194
TI  - Immunotherapy for acute myeloid leukemia.
AB  - Immunotherapeutic strategies have become part of standard cancer treatment.
      Chimeric and humanized antibodies have demonstrated activity against a variety of
      tumors. Although the humanized anti-CD33 antibody HuM195 has only modest activity
      against overt acute myeloid leukemia (AML), it can eliminate minimal residual
      disease in acute promyelocytic leukemia. High-dose radioimmunotherapy with b
      particle-emitting isotopes targeting CD33, CD45, and CD66 can potentially allow
      intensification of antileukemic therapy before hematopoietic stem cell
      transplantation. Conversely, a-particle immunotherapy with isotopes such as
      bismuth-213 or actinium-225 offers the possibility of selective tumor cell kill
      while sparing surrounding normal tissues. Targeted chemotherapy with the anti
      CD33- calicheamicin construct gemtuzumab ozogamicin has produced remissions in
      relapsed AML and appears promising when used in combination with standard
      chemotherapy for newly diagnosed AML. T-cell recognition of peptide antigens
      presented on the cell surface in combination with major histocompatibility
      complex antigen provides another potentially promising approach for the treatment
      of AML.

PMID- 16091195
TI  - Linking KSHV to human cancer.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8
      (HHV-8), has been linked to several malignancies in humans. KSHV is the etiologic
      agent associated with the development of Kaposi's sarcoma (KS), primary effusion
      lymphoma (PEL), and multicentric Castleman's disease (MCD). KSHV is a double
      stranded DNA virus that has been classified as a gammaherpesvirus. Here, we
      review the association of KSHV with human cancer, viral genes that may
      potentially be involved in the neoplastic process, and current therapies used to
      treat KS, PEL, and MCD.

PMID- 16091196
TI  - Diffuse large B-cell lymphomas with plasmablastic differentiation.
AB  - Recent evidence suggests that diffuse large B-cell lymphoma (DLBCL) with
      plasmablastic differentiation represents a clinically heterogeneous spectrum with
      different clinicopathologic characteristics representing distinct entities.
      Subtypes of DLBCL with plasmablastic features and terminal B-cell differentiation
      include plasmablastic lymphoma (PBL) of oral mucosa type; PBL with plasmacytic
      differentiation; primary effusion lymphoma (PEL); KSHV-positive solid
      lymphoma/extracavitary PEL/HHV-8 associated DLBCL; and DLBCL expressing ALK. In
      contrast, PBL associated with multicentric Castleman disease, DLBCL with
      secretory differentiation, pyothorax-associated lymphoma, and atypical Burkitt
      lymphoma with plasmacytoid differentiation have morphologic appearances of plasma
      cell differentiation but maintain a mature B-cell (CD20 positive) phenotype.
      These tumors as well as extramedullary plasmablastic tumors secondary to multiple
      myeloma or plasmacytomas are included in the differential diagnosis. In this
      review, we discuss recently described clinicopathologic insights, case
      observations, and recently reported molecules involved in terminal B-cell or
      plasma cell differentiation and their possible roles in disease pathogenesis.

PMID- 16091198
TI  - Mitotic rate and younger age as predictors of sentinel lymph node positivity.

PMID- 16091197
TI  - New developments in immunotherapy for non-Hodgkin's lymphoma.
AB  - The clinical development of immunotherapy with rituximab (chimeric anti-CD20
      monoclonal antibody) has markedly affected the treatment approach for patients
      with B-cell non-Hodgkin's lymphoma (NHL). Rituximab was initially evaluated in
      relapsed indolent lymphoma and has substantial activity in this setting both
      alone and in combination with chemotherapy. Ongoing efforts in indolent NHL are
      seeking to optimize the dose and schedule of rituximab through "maintenance"
      strategies exploring chemotherapy-rituximab combinations and the use of other
      biologic agents or antibodies that may enhance activity when employed together
      with rituximab. Other studies in indolent NHL suggest that radiolabeled anti-CD20
      antibodies (such as I-131 tositumomab and Y-90 ibritumomab tiuxetan) may be
      useful in relapsed and refractory disease and have potential utility as part of
      initial treatment as well. In diffuse large B-cell lymphoma, the addition of
      rituximab to CHOP chemotherapy can improve survival, though benefits are more
      limited in mantle cell lymphoma. Further studies of unlabeled and radiolabeled
      immunotherapies are ongoing in order to optimize their use for maximal clinical
      benefit.

PMID- 16091199
TI  - Molecular staging in stage II and III melanoma patients.

PMID- 16091200
TI  - Tumor cell and circulating markers in melanoma: diagnosis, prognosis, and
      management.
AB  - The search is on for biomarkers for use in the diagnosis, staging, prognosis, and
      management of patients with melanoma. As with many types of cancer, the
      hematogenous spread of melanoma is a bad prognostic sign, and many groups have
      attempted to detect circulating melanoma cells in patients with different stages
      of melanoma. Some studies have used direct extraction of intact tumor cells from
      the peripheral blood and others the detection of surrogate markers of circulating
      melanoma cells, such as tyrosinase or MART-1. However, a correlation between the
      detection of intact melanoma cells in the circulation and prognosis is
      controversial. Many other biomarkers have also been studied, including lactate
      dehydrogenase, S100, TA90, and C-reactive protein. Much progress has been made,
      and preliminary studies have shown promise with many of these markers. Finally,
      the detection of tumor-specific circulating DNA has shown promise as a prognostic
      and diagnostic marker of disease in melanoma as well. In this review we examine
      the most promising biomarkers for use in patients with cutaneous melanoma.

PMID- 16091201
TI  - Immunotherapy for melanoma: the good, the bad, and the future.
AB  - The past 20 years have seen remarkable advances in our understanding of the
      molecular and cellular processes controlling the development of an anticancer
      immune response. These advances have spawned a renaissance in the field of cancer
      immunotherapy, the original targeted therapy, during which investigators have
      pushed the envelope and translated promising strategies into investigational
      therapeutics in patients with cancer. An approach that combined nonmyeloablative
      lymphodepleting chemotherapy with adoptive transfer of tumor-specific CD4 and CD8
      T cells exhibited an initial objective response rate of 51% for patients with
      stage IV melanoma. Although this strategy is extremely challenging, one can
      expect technological advances that may simplify this approach and further improve
      outcome.

PMID- 16091202
TI  - New concepts in asthma pathophysiology.

PMID- 16091205
TI  - WHIM syndrome: a defect in CXCR4 signaling.
AB  - The study of inherited immunodeficiencies has proven valuable in elucidating
      molecular signaling cascades underlying the developmental and functional
      regulation of the human immune system. The first example of a human immunologic
      disease caused by mutation of a chemokine receptor was provided by WHIM (warts,
      hypogammaglobulinemia, infections, and myelokathexis) syndrome, a rare, combined
      immunodeficiency featuring an unusual form of neutropenia. Subsequent studies
      following the initial description of mutations in the CXCR4 gene have revealed a
      striking concordance in the types of mutations observed, suggesting that impaired
      regulation of receptor signaling by truncation of the cytoplasmic tail domain is
      an essential aspect in disease pathogenesis. Biochemical studies have provided
      support for the model that impaired receptor downregulation leads to the
      characteristic immunologic and hematologic disturbances. Interestingly, these
      genetic studies have also identified phenocopies with the same clinical features
      but without mutation of CXCR4, suggesting that mutations in as yet
      uncharacterized downstream regulators of the receptor may be involved in a
      proportion of cases.

PMID- 16091206
TI  - The role of the FOXP3 transcription factor in the immune regulation of allergic
      asthma.
AB  - Unbalanced immune reactions against allergens are caused by Th2 cells, which are
      the basis of immunoglobulin E (IgE)-mediated symptoms of allergy and asthma.
      Although Th2 cells are essential for allergy, they are not sufficient to cause
      disease, because regulatory T cells (Tregs) control their activity and expansion.
      Therefore, Tregs are assumed to play an important role not only in the
      sensitization but also in established allergic disease under therapy. A key
      factor of Tregs is FOXP3, which, upon expression, is sufficient to induce
      regulatory T-cell phenotypes. The initiation and suppressive function of FOXP3
      and Tregs in the context of allergic asthma are discussed in this review.

PMID- 16091207
TI  - New insights into the role of the complement pathway in allergy and asthma.
AB  - Despite extensive inquiry, the mechanisms underlying the pathophysiology of
      allergic diseases remain unknown. Recently, there has been a resurgence of
      interest in the role of the innate immune mediators of the complement pathway in
      asthma pathogenesis, particularly the anaphylatoxins (C3a, C5a). The emerging
      paradigm is that C3a production at the airway surface serves as a common pathway
      for the induction of airway hyperresponsiveness to a variety of asthma triggers
      (ie, allergens, viral infections, particulate matter, ozone, smoke), whereas
      C5/C5a plays a dual immunoregulatory role by protecting against Th2-mediated
      immune responses during initiation of responses and a proinflammatory role once
      immune responses are established. Support for a causal role for altered
      anaphylatoxin production in human disease comes from reports of exaggerated
      complement production in the lungs of asthmatics as well as the association of
      asthma with polymorphisms in C3/C3aR genes. Herein, we explore our current
      understanding of the role of complement activation in asthma pathogenesis and
      highlight the potential of targeting complement pathways for therapeutic drug
      development.

PMID- 16091208
TI  - Granulomatous disease in common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a primary immunodeficiency of unknown
      etiology characterized by low levels of immunoglobulin (Ig)G, failure to make
      specific antibodies in response to infection or immunization, and variable T-cell
      abnormalities. Multisystemic granulomatous disease is a well-documented
      complication of CVID, and its presence is associated with significant morbidity
      and early mortality. Although the lung is the most common organ system affected,
      granulomas are also found frequently in other organs, including skin, liver,
      spleen, and the gastrointestinal tract. Autoimmune disorders are common in these
      patients, and there appears to be an increased propensity to develop
      lymphoproliferative disorders. Common physical, radiographic, and laboratory
      abnormalities in patients with CVID and granulomatous disease include
      splenomegaly, hilar and mediastinal lymphadenopathy with ground glass or nodular
      opacities in the lung parenchyma, and reduced T-cell numbers and function. The
      etiology of granulomatous disease in patients with CVID is unknown, and optimal
      treatment of granulomatous disease in CVID remains to be established. Further
      studies are needed to elucidate the underlying etiology of granulomatous
      lymphoproliferative interstitial lung disease and to delineate appropriate
      treatments for this disease.

PMID- 16091211
TI  - Immunobiology of grass pollen allergens.
AB  - Among pollen allergens, grass pollen allergens are some of the most frequent
      contributors to allergic symptoms. Substantial progress has been made since the
      1960s in the identification and characterization of the grass allergens. Members
      of this group belong to the Poaceae family, and have been classified into 13
      distinct groups based on their structure, and their biological and immunologic
      properties. The major contributors to allergy and, hence, most studied among the
      grass allergens, are those belonging to groups 1 and 5. This review is focused on
      the structure and immunobiology of the grass allergens and highlights how recent
      advances in the field have contributed to superior diagnosis and immunotherapy
      for allergy to grass pollens.

PMID- 16091212
TI  - Structural biology of allergens.
AB  - Major allergens may have special aerobiological properties and allergenic
      structures. It would also be instructive to consider the properties of
      nonallergens and nonallergenic responses. In some cases, nonallergenic responses
      appear to result from a lack of antigenicity and in others from regulation.
      Proteolytic activity has been proposed as an adjuvant for allergenicity, but
      lipid binding is far more common and is found for more than 50% of the major
      allergens. Such structures can enhance allergenicity via Toll-like receptor (TLR)
      or CD1 pathways. TLR signaling can enhance both Th1 and Th2 responses and be
      induced by peptides as well as nonproteinaceous ligands.

PMID- 16091213
TI  - Assessment of indoor allergen exposure.
AB  - Of the four modes of treating human allergic disease, avoidance or separation of
      the allergic patient from the allergen source is most effective and least
      expensive. The clinical immunology laboratory has established efficient and
      inexpensive "reservoir" dust sampling and processing procedures to obtain a
      surface dust specimen that reflects the allergen burden of the environment.
      Following extraction, allergens are quantified by reproducible, validated
      immunoenzymetric assays for the quantification of "indicator" aeroallergen levels
      in home, school, and work environments. In this paper, the strategies and methods
      for collecting and processing dust samples are discussed, and assays are reviewed
      for quantifying indoor aeroallergen exposure from dust mites (Der p 1 and 2, Der
      f 1 and 2), animals (cat: Fel d 1; dog: Can f 1; mouse: Mus m 1; rat: Rat n 1),
      and insects (cockroach: Bla g 1 and 2). Accurate quantification of the levels of
      allergen in indoor environments facilitates avoidance therapy by identifying
      environmental risk factors for asthma and allergy exacerbation and allowing the
      allergic patient to monitor the effectiveness of environmental remediation
      actions.

PMID- 16091214
TI  - Mite allergens.
AB  - There is an increasing awareness of the health implications of mite sensitivity,
      as it is closely related to asthma. Mite allergy constitutes a complex worldwide
      problem, with sanitary and economical implications. Not only are mite species
      present in house dust, producing potent allergens, but other, less studied
      species are also responsible for significant allergic reactions in occupational
      settings. In this review, we focus on the growing number of mite species that are
      implicated in allergic cutaneous and respiratory diseases in humans. Mite allergy
      is not restricted only to the human "indoor" environment, because numerous
      reports clearly demonstrate that many species that can induce sensitization and
      symptoms are encountered in occupational settings. An important component of
      allergy research is the evaluation of the allergenic cross-reactivity to verify
      to what extent different mite species have unique, species-specific, or cross
      reactive allergens. The results of these investigations have important clinical
      consequences for the diagnosis and treatment of allergic diseases.
      Internationally standardized mite extracts are needed to compare sensitization
      rates around the world and clearly establish risk factors associated with
      sensitization and asthma. In spite of recent controversial results, a significant
      reduction in the exposure to mite allergens continues to be an important
      challenge and one of the main goals in the treatment of mite-induced respiratory
      symptoms. In many cases, this reduction must be achieved in the workplace as well
      as in the home environment.

PMID- 16091215
TI  - Cockroach allergens.
AB  - Cockroaches produce several potent allergens associated with sensitization and
      the development of asthma. Many of these allergens have been cloned and produced
      as biologically active recombinant proteins. Three-dimensional structure and
      molecular modeling, in addition to studies on the biological functions of these
      proteins in the cockroach, have provided new insights into the ability of these
      allergens to cause immunoglobulin E antibody responses. Recent studies have
      pointed to a potential role of recombinant cockroach allergens for diagnosis and
      the development of novel therapeutic strategies that may benefit cockroach
      allergic patients.

PMID- 16091216
TI  - Animal allergens.
AB  - Animal allergen exposure in early childhood and its relationship to the
      development of atopic disease is a subject that has been evolving rapidly.
      Recently, several well-designed studies have helped elucidate previous, often
      conflicting findings on this topic. In addition, results from studies on farm
      animal exposure have added strength to data on early dog and cat exposure. In
      this paper, we review several recent studies that have helped clarify the
      relationship between early animal-allergen exposure and childhood atopic disease.

PMID- 16091217
TI  - Human herpesvirus 8: biology and role in the pathogenesis of Kaposi's sarcoma and
      other AIDS-related malignancies.
AB  - Human herpesvirus type 8, or Kaposi's sarcoma-associated herpesvirus (KSHV), is
      the only known human g(2) herpesvirus (rhadinovirus) and the most recently
      discovered tumor virus. KSHV is associated with Kaposi's sarcoma and two other
      lymphoproliferative disorders in the AIDS setting: primary effusion lymphoma and
      the plasma cell variant of multicentric Castleman's disease. This review offers
      an update on the epidemiology and the role of KSHV genes in the development of
      disease.

PMID- 16091218
TI  - Advances in understanding immunologic control of HIV infection.
AB  - Over the past several years, the progress made in understanding the cellular
      immune response to HIV is likely greater compared to any other time since the
      beginning of the worldwide epidemic. This progress has largely been made possible
      by technical advances that have permitted a much more quantitative and highly
      detailed study of virus-specific cellular immunity in humans than was previously
      available. However, despite intensive study of the HIV-specific cellular immune
      response, we do not fully understand the nature of immunologic control in some
      rare cases and lack of control in most of untreated patients. It has become
      increasingly clear that HIV replication is poorly controlled in most untreated
      patients, despite a high-frequency HIV-specific cellular immune response.
      Therefore, attention has turned to qualitative features of the immune response
      that may dictate restriction of viral replication. Because most vaccines in
      preclinical or clinical testing rely on cellular immune responses that may alter
      disease progression but are unlikely to prevent infection, understanding these
      qualitative features is of particular importance. Further study could yield
      critical information for inducing effective immunity in vaccinees, preventing the
      loss of control of viral replication on the infection of vaccinees, or inducing
      immunologic control in infected humans.

PMID- 16091219
TI  - Current advances in HIV vaccines.
AB  - Development of a safe and preventive HIV-1 vaccine is a high priority. Recent
      advances in HIV vaccine development include an improved understanding of HIV
      envelope structure, development of techniques that enable a detailed analysis of
      vaccine-induced immune responses in humans, expansion of the pipeline of
      promising candidate vaccines, and completion of the first vaccine efficacy
      trials. A common feature of several preventive vaccine strategies in early
      clinical trials is their ability to attenuate clinical disease rather than
      completely prevent HIV infection in nonhuman primates. One or more candidate
      vaccines will likely advance into efficacy trials within the next few years,
      while efforts to identify new designs that induce broadly neutralizing antibodies
      continue with incremental success.

PMID- 16091220
TI  - Vaginal microbicides: a novel approach to preventing sexual transmission of HIV.
AB  - The AIDS epidemic continues its unrelentless expansion. According to the Joint
      United Nations Programme on HIV/AIDS, there are more than 40 million people
      living with HIV, and more than 15,000 new infections occur every day. One
      approach to curbing HIV is the development of topical microbicidal agents or
      microbicides. These are compounds designed to protect the body's mucosal surfaces
      from infection by sexually transmitted disease-causing pathogens, including HIV.
      Several candidates are in preclinical stages; however, only a handful have been
      tested in humans for safety, and even fewer are ready for clinical efficacy
      trials. In this update, we describe microbicide research and development,
      including preclinical screening algorithms, ideal properties, compounds in the
      pipeline, and future prospects. This review is based on a previous work, which
      has been updated to contain new information, especially regarding microbicide
      candidates in preclinical and clinical stages of development.

PMID- 16091221
TI  - Updated clinical pharmacologic considerations for HIV-1 protease inhibitors.
AB  - Many data associate low protease inhibitor plasma concentrations with suboptimal
      virologic responses, whereas fewer data associate high plasma concentrations with
      toxicity. Knowledge of relationships between concentrations and virologic
      response is important because significant variability in concentrations exists
      among patients. For antiretroviral-naive patients, target trough concentrations
      have been suggested on the basis of retrospective associations with virologic
      responses. Two prospective studies demonstrated improved virologic responses when
      indinavir and nelfinavir doses were managed based on these troughs.
      Investigations among antiretroviral-experienced patients have identified a
      relationship between the trough concentration and the in-vitro susceptibility of
      the patient's virus with virologic outcome. However, differences in virologic
      response may further depend on other pharmacologic factors, such as protein
      binding, intracellular kinetics, function of drug transporters, and the activity
      of other drugs in the regimen. In the future, dosing strategies that accommodate
      the variability in pharmacokinetics and pharmacodynamics may improve virologic
      outcomes.

PMID- 16091222
TI  - Viral and cellular dynamics in HIV disease.
AB  - The control mechanisms that maintain a steady state viral load during chronic HIV
      1 infection are critical to understanding the pathophysiology of HIV disease. The
      conceptual features of the two alternative models of viral control, referred to
      in this article as target cell limitation and immune control, are compared to the
      data regarding the viral and cellular dynamics of HIV-1 infection and the pattern
      of changes induced by effective antiretroviral drug therapy. The available data
      support the model that an antigen-driven immune response is the primary mechanism
      that limits viral growth in vivo.

PMID- 16091223
TI  - HIV accessory proteins and surviving the host cell.
AB  - Human immunodeficiency virus generates the accessory proteins Nef, viral
      infectivity factor (Vif), viral protein R, and viral protein U or viral protein X
      during viral replication in host cells. Although the significance of these
      accessory proteins is often lost in vitro, they are essential for viral
      pathogenesis in vivo. Therefore, these proteins have much potential as antiviral
      targets. Recent data reveal Vif perturbs an ill-defined antiviral pathway in host
      cells allowing HIV replication. These data highlight a common feature among HIV
      accessory proteins in manipulating the host to aid viral pathogenesis. Therefore,
      these new insights into Vif and other HIV accessory proteins are reviewed,
      emphasizing host cell interactions and new targets for therapeutic intervention.

PMID- 16091224
TI  - Antiretroviral therapy: when and what to start-- an American perspective.
AB  - The major US treatment guidelines now recommend starting antiretroviral therapy
      (ART) later in the course of HIV infection because of an increasing awareness of
      the difficulties associated with these regimens. Most of the data to support this
      change come from observational cohort studies. When deciding to start ART,
      several patient-specific factors and other issues should be considered. Because
      of the many choices for initial ART, clinicians should individualize the choice,
      taking into account regimen antiretroviral potency, durability, side effects,
      toxicities, and convenience to ensure a sustained clinical benefit for the
      patient.

PMID- 16091225
TI  - Primary HIV Infection.
AB  - Primary HIV infection refers to the events surrounding acquisition of HIV
      infection. It is associated with a nonspecific clinical syndrome that occurs 2 to
      4 weeks after exposure in 40% to 90% of individuals acquiring HIV. Patients
      identified before seroconversion often have very high plasma HIV RNA titers that,
      without treatment, gradually decrease to reach a set point. Treatment of primary
      HIV infection with highly active antiretroviral therapy does not prevent
      establishment of chronic infection. However, very early therapy could potentially
      decrease the viral set point, prevent viral diversification, preserve immune
      function, improve clinical outcomes, and decrease secondary transmission. These
      benefits have not yet been definitely demonstrated. Transmission of viral strains
      with decreased susceptibility to antiviral drugs has led to recommendations for
      resistance testing in primary infection before initiation of therapy.
      Immunomodulators and vaccines are also under study as adjuvant therapy for
      treatment of primary HIV infection.

PMID- 16091226
TI  - Virologic and immunologic response to highly active antiretroviral therapy.
AB  - Highly active antiretroviral therapy (HAART) delays clinical progression by
      suppressing viral replication, measured by a substantial reduction in HIV RNA,
      allowing the immune system to reconstitute, measured in most studies by an
      increase in CD4 cells. These virologic and immunologic consequences do not occur
      uniformly among HAART users. Markers of HIV disease stage at the time of HAART
      initiation are critical determinants of the progression while receiving HAART. In
      this report, we review studies describing the heterogeneous virologic and
      immunologic progression after the initiation of HAART, discuss methodologic
      concerns in the study of the response of biomarkers, and update findings obtained
      in the Multicenter AIDS Cohort Study, which show that CD4 cell count, history of
      antiretroviral therapy, and age at the time of initiation are independent
      determinants of response.

PMID- 16091227
TI  - New antiretroviral agents for the treatment of HIV infection.
AB  - Issues, such as complexity, tolerability, and drug resistance and cross
      resistance, limit the effectiveness of current antiretroviral regimens and make
      the continued development of newer agents important, despite the availability of
      20 approved drugs for the treatment of HIV infection. Many new compounds are in
      development in existing classes: nucleoside and nucleotide analogue reverse
      transcriptase inhibitors (eg, D-d4FC and SPD754), non-nucleoside analogue reverse
      transcriptase inhibitors (eg, capravirine and TMC125), and protease inhibitors
      (eg, tipranavir and TMC114). In addition, newer classes of antiretroviral drugs,
      such as HIV entry inhibitors (eg, TNX-355, SCH 417690, UK-427,857, AMD 11070),
      that target the first step in the HIV life cycle are under development. Continued
      improvement in the treatment of HIV infection will result from the availability
      of convenient, well-tolerated, and affordable drugs with potent and durable
      antiretroviral activity.

PMID- 16091228
TI  - Drug interactions with antiretrovirals.
AB  - The recent development of new antiretroviral drugs, along with the evolution in
      clinical practice guidelines that include the recommendation of the use of three-
      to four-drug combination regimens for achieving optimal suppression of viral
      replication, has focused clinicians on the relevance of drug-drug interactions in
      the chronic care of HIV-infected individuals. However, the routine clinical
      management of drug interactions is complicated by our expanding knowledge of the
      physiologic mechanisms underlying pharmacokinetic interactions, particularly as
      they relate to drug transport and tissue distribution (eg, P-glycoprotein) and
      biotransformation (hepatic cytochrome p450 mono-oxygenase induction and
      inhibition). This review provides an updated summary of key drug interactions
      that have been reported since its initial publication.

PMID- 16091229
TI  - Management of antiretroviral therapy in neonates, children, and adolescents.
AB  - There have been tremendous advances in the prevention of maternal-to-child
      transmission of HIV and treatment of HIV-infected children and adolescents.
      Although multiple classes of anti-HIV drugs are available that can control viral
      replication and stabilize immune function when used in combination, patients and
      their providers must also manage complex and frequently toxic regimens. This
      article updates our original report that summarizes official National Institutes
      of Health guidelines for the prevention of perinatal HIV infection and the
      management of pediatric and adolescent HIV infection and provides the most
      current updates on indications for therapy, recommended first-line therapy,
      criteria for changing therapy, salvage therapy, novel management strategies, and
      a comprehensive summary of available antiretroviral agents.

PMID- 16091230
TI  - HIV and the kidney: a status report after 20 years.
AB  - The first association between HIV-1 infection and kidney disease was made in 1984
      and much has been learned over the past 20 years. In recent years, more effective
      therapies for HIV-1 infection and its associated opportunistic infections have
      led to improved patient survival. However, with prolonged survival, morbidity
      associated with renal disease has also increased. Among the multiple
      glomerulopathies that can affect patients with HIV, focal segmental
      glomerulosclerosis (FSGS) is most common and frequently leads to end-stage renal
      disease. Although the precise mechanisms of HIV-associated FSGS remain to be
      elucidated, it appears that host genetic susceptibility, direct infection of the
      renal epithelium, and toxicity of one or more viral accessory protein contribute.
      Therapy for HIV-associated FSGS includes control of blood pressure and the use of
      angiotensin antagonist therapy. A randomized trial of angiotensin receptor
      blocker will be initiated shortly. Drug-related nephropathies are also common,
      manifesting as acute renal failure, nephrolithiasis, and interstitial nephritis.
      Tenofovir, a newer nucleoside analogue, has recently been implicated in causing
      tubular toxicity, although the incidence is low. Appropriate screening for renal
      dysfunction can minimize the likelihood of progressive renal injury in all
      patients with HIV-1 infection.

PMID- 16091231
TI  - Management of HIV-infected patients with multidrug-resistant virus.
AB  - Treatment-experienced patients with HIV may harbor virus that has accumulated
      several mutations conferring decreased susceptibility to one or more
      antiretroviral drugs. For clinicians treating these patients, identifying a
      tolerable antiretroviral regimen with a reasonable chance of a durable virologic
      effect represents a major challenge. The first priority is to identify and
      correct the mechanisms responsible for previous treatment failure. Resistance
      testing and drug level monitoring may be useful in this setting. The patient's
      history of antiretroviral drug tolerability, comorbidities, and concomitant
      medications should be considered. Patients embarking on multiple-drug regimens
      will require close monitoring for adherence, toxicities, and drug-drug
      interactions. The guiding principle when constructing a rescue or salvage regimen
      is to achieve a cumulative activity score greater than 2, recognizing that some
      agents will have only partial activity. Some new drugs are available that may be
      helpful if used carefully with an active background regimen.

PMID- 16091232
TI  - Immune restoration inflammatory syndromes: apparently paradoxical clinical events
      after the initiation of HAART.
AB  - Immune reconstitution occurs after initiation of highly active antiretroviral
      therapy in immunodeficient HIV-positive individuals. Unexpected deterioration of
      inflammatory disease and atypical clinical features resembling symptoms of
      autoimmune disease may arise. These atypical inflammatory disorders, synonymously
      summarized as immune reconstitution syndrome, immune restoration disease, and
      immune restoration inflammatory syndrome (IRIS), are caused by augmentation of
      inflammation during immune reconstitution in an immunocompromised host. These
      disorders have to be distinguished from intercurrent infection and rheumatic
      disease, respectively. Treatment of IRIS consists of elements for both potential
      differential diagnoses (ie, anti-inflammatory and immunosuppressive drugs, such
      as in autoimmune disorders and antimicrobial chemotherapy, to decrease the burden
      of pathogen, such as in infectious disease). Therefore, awareness for IRIS is of
      increasing importance from a clinical point of view. However, diagnostic criteria
      and standards of treatment are still preliminary.

PMID- 16091233
TI  - Hepatitis C virus infection in HIV-infected patients.
AB  - Because of shared routes of transmission, hepatitis C and HIV coinfection is
      common in the United States, affecting 15% to 30% of HIV-infected individuals. In
      the era of highly effective antiretroviral therapy, hepatitis C virus (HCV)
      related liver disease has emerged as a significant cause of morbidity and
      mortality. Accordingly, the Infectious Diseases Society of America and the
      American Association for the Study of Liver Disease guidelines for the management
      of HCV recommend that patients with HIV/HCV undergo medical evaluation for HCV
      related liver disease and consideration for HCV treatment and, if indicated,
      orthotopic liver transplantation. However, the treatment of patients with HIV/HCV
      is complicated by the relatively high prevalence of medical and psychiatric
      comorbidities and the challenges of anti-HCV therapy in the setting of HIV
      disease and antiretroviral therapy. Nonetheless, recently completed randomized
      controlled trials provide evidence of the safety, tolerability, and efficacy of
      HCV treatment with pegylated interferon-alpha plus ribavirin in HIV-infected
      individuals. This review focuses on the epidemiology, natural history, and
      management of HCV in the HIV-infected patient.

PMID- 16091234
TI  - Controlling neuropathic pain in HIV.
AB  - Neuropathic pain is associated with numerous systemic illnesses, including HIV
      infection. The diagnosis and management of peripheral neuropathy presents
      diagnostic and therapeutic challenges. Among various forms of HIV-associated
      peripheral neuropathies, distal symmetrical polyneuropathy (DSP) is the most
      common. DSP may be caused or exacerbated by neurotoxic antiretrovirals,
      particularly the dideoxynucleoside analogues (d-drugs). Selection of appropriate
      pharmacologic intervention for peripheral neuropathy should be based on efficacy,
      safety, ease of administration, and cost. We review treatment options for painful
      HIV neuropathy, including experimental agents studied in recent and ongoing
      clinical trials.

PMID- 16091235
TI  - Syphilis in the HIV-infected patient: an update on epidemiology, diagnosis, and
      management.
AB  - After a decade of unprecedented declines, incidence of early-stage syphilis in
      the United States and Europe has increased significantly since 2000. These cases
      have occurred at disproportionately elevated rates among people infected with
      HIV. Speculation continues as to whether the clinical spectrum of syphilis is
      qualitatively different among those individuals who are HIV infected. Recent data
      suggest that individuals who are immune compromised because of HIV have a higher
      likelihood of developing neurosyphilis. Recommendations for treatment of syphilis
      remain the same for patients with and without HIV.

PMID- 16091236
TI  - Changes in HIV and AIDS in the United States: entering the third decade.
AB  - The epidemiology of the HIV transmission in the United States has changed
      considerably since the epidemic began. Our increased understanding of the virus
      has fostered development of new treatments to prolong life, and vaccine research
      has increased hope for those at risk in both developed and less developed
      countries. In this review, we provide information about current trends in HIV and
      AIDS among those in the United States most affected by the epidemic.

PMID- 16091237
TI  - Management of occupational and nonoccupational postexposure HIV prophylaxis.
AB  - The principles of managing patients with recent HIV exposures are similar whether
      the exposure occurs in an occupational or nonoccupational setting. For both
      settings, clinicians should 1) assess the likelihood that HIV and other
      bloodborne viruses will be transmitted as a consequence of the exposure; 2)
      advise the patient about the risks and benefits of treatment; 3) choose an
      appropriate antiretroviral treatment regimen (if the decision is made to treat);
      4) screen for other illnesses that may complicate treatment or follow-up; 5)
      counsel patients about the importance of adhering to treatment; 6) promote safe
      sex practices and methods to avoid future exposures; 7) follow the patient for
      potential side effects of treatment; 8) provide follow-up care including repeat
      HIV testing for seroconversion, surveillance for primary HIV infection, and
      reinforcement of counseling messages.

PMID- 16091238
TI  - Efforts to control sexually transmitted infections as a means to limit HIV
      transmission: what is the evidence?
AB  - There is overwhelming and compelling evidence that control efforts for STI have a
      major role to play in the prevention of HIV transmission. Community-based
      randomized controlled trials are set as the highest standard of evidence for
      showing the efficacy of STI interventions to prevent HIV transmission. The
      negative results of recent randomized controlled trials have cast doubt on the
      positive findings of the Mwanza study. Deeper analysis of the result of these
      trials has improved understanding of the role of STI interventions and augmented
      the wealth of evidence provided by numerous epidemiological and biomedical
      studies. Apart from the biological impact of effective treatment of curable STIs
      on HIV transmission, clinical services also support the reduction of HIV-risk
      behaviors. STI interventions should limit the scale of the impending epidemics in
      Asia and Eastern Europe, depending on the priority that they are given by
      governments and major donor agencies.

PMID- 16091239
TI  - Adherence to antiretroviral therapy: an update of current concepts.
AB  - The remarkable effectiveness of combination antiretroviral therapy (CART) in the
      treatment of HIV infection has placed a high premium on long-term adherence to
      therapy. Adherence levels to CART among HIV-infected individuals are similar to
      adherence levels with chronic medical conditions, such as diabetes and
      hypertension. However, unlike chronic medical conditions, medication adherence
      that is insufficient to maintain suppression of HIV replication will lead to drug
      resistance. Combination antiretroviral therapy regimen complexity and side-effect
      burden are clearly linked to adherence and are likely to be the factors most
      amenable to intervention. Adherence interventions that are multifaceted,
      flexible, and protracted are the most likely to be successful. Owing to the great
      benefits of CART even the small to modest gains in adherence that are achievable
      with adherence programs may prove to be cost effective.

PMID- 16091240
TI  - The evolving role of HIV counseling and testing in resource-limited settings: HIV
      prevention and linkage to expanding HIV care access.
AB  - The role of voluntary counseling and testing (VCT)of HIV in resource-limited
      settings has recently broadened from primarily that of a prevention intervention
      to its identification as the key entry point into expanding access to life-saving
      antiretroviral therapy, additional HIV-specific medical care, and other support
      services. To fulfill this expanded mandate, calls for routine counseling and
      testing in diverse health care settings, in addition to other innovative
      approaches to traditional VCT, are emerging. The efficacy and cost-effectiveness
      of traditional facility-based VCT with respect to risk-behavior reduction of HIV
      have been demonstrated rigorously in resource-limited settings. Additional
      research is needed urgently to evaluate the feasibility, acceptability, and
      effectiveness of streamlined counseling and testing interventions that seek to
      reach as many individuals as possible to meet dual prevention and treatment
      goals.

PMID- 16091241
TI  - The HIV epidemic among individuals with mental illness in the United States.
AB  - People with depression and other mental illness comprise a growing proportion of
      individuals living with HIV in the United States; at the same time, the
      prevalence of HIV among mentally ill individuals is at least seven times higher
      than in the general population. Individuals with mental illness are particularly
      vulnerable to infection with HIV because of several factors, including the higher
      prevalence of poverty, homelessness, high-risk sexual activities, drug abuse,
      sexual abuse, and social marginalization found in this population. Nevertheless,
      mentally ill individuals are often not screened for HIV and may not be
      appropriately targeted in current HIV prevention efforts. Moreover, despite
      widespread access to antiretroviral treatment in the United States, HIV outcomes
      among mentally ill individuals continue to be poor. This disparity can be
      explained by several interrelated factors, including lower rates of highly active
      antiretroviral therapy (HAART) utilization, lower rates of adherence to HAART,
      and immunologic changes associated with mental illness itself. We need to improve
      our design of prevention, screening, and treatment programs to better reach
      individuals with comorbid HIV and mental illness.

PMID- 16091242
TI  - Therapeutic HIV vaccines: an update.
AB  - The goal of therapeutic immunization in HIV infection is to induce strong and
      sustained immune responses against HIV. Several arguments suggest that the immune
      system may contain HIV replication in the long term before declining. The potency
      on new antiviral regimens in clinic has provided an opportunity to improve the
      control of the virus replication by the immune system. In clinical terms, this
      might allow patients to delay or to stop antiviral therapy and to minimize the
      duration of the exposition to antiviral drugs.

PMID- 16091243
TI  - The innate immune system and HIV pathogenesis.
AB  - Innate immunity represents the first line of defense against microbial
      infections. The innate immune system is activated by conserved structures present
      on most pathogens and profoundly regulates subsequent adaptive immune responses.
      HIV is notorious for evading and disrupting the immune system. Although HIV
      directly targets and gradually destroys the adaptive immunity, it has become
      clear that the virus also perturbs the components of the innate immune system. In
      this paper, we review the role of two innate lymphocyte subsets, natural killer
      and natural killer T cells, that are disrupted during HIV infection.

PMID- 16091244
TI  - CD4+ T-cell depletion in HIV infection: killed by friendly fire?
AB  - Recent studies have emphasized the role of a chronic, generalized activation of
      the immune system as a prominent cause of CD4+ T-cell depletion in HIV-infected
      patients. The HIV-induced immune activation is a strong predictor of disease
      progression in humans, and lack of immune activation is a key feature of
      nonpathogenic simian immunodeficiency virus (SIV) infection of natural hosts. The
      mechanisms by which immune activation induces CD4+ T-cell depletion are still
      incompletely understood, but likely involve changes in the complex dynamics of
      the naive, memory, and effector subsets of T cells. A better understanding of how
      HIV-induced immune activation leads to CD4+ T-cell depletion may provide new
      targets for immune-based interventions that could be used, in addition to
      standard antiretroviral therapy, to slow disease progression in HIV-infected
      individuals.

PMID- 16091245
TI  - Thymic function in HIV infection.
AB  - Current models hold that CD4+ depletion occurs as a result of direct and indirect
      effects of HIV, which both kill peripheral CD4+ cells and prevent adequate
      regeneration. Although age-associated involution diminishes thymic reserve and
      HIV is clearly thymotoxic, clinical trials have nonetheless shown that large
      proportions of patients who sustain adequate control of viral replication with
      highly active antiretroviral therapy (HAART) will demonstrate some evidence for
      thymic-dependent immune reconstitution, which is associated with improved immune
      competence. Furthermore, patients with insufficient or absent immune
      reconstitution following HAART generally lack evidence for thymopoiesis. Current
      studies are focused on improving our understanding of the causes for thymic
      failure in HIV infection. Recent work has demonstrated that some HIV strains,
      especially those that are CXCR4 trophic, are more thymotoxic and may contribute
      to irreversible thymic damage in this population.

PMID- 16091246
TI  - The role of viral fitness in HIV pathogenesis.
AB  - The development of clinical symptoms, and clinical progression among persons
      infected with HIV-1 is the manifestation of the effects of the pathogenic viral
      life cycle of HIV-1. Individual variants of HIV-1 vary widely in features that
      determine viral fitness and virulence. HIV-1 exploits host antiviral responses,
      the APOBEC3G cytidine deaminase, and the low-fidelity HIV-1 reverse
      transcriptase, to ensure new variants with novel phenotypic features are
      continually present for expansion in response to changing conditions in the host,
      such as immune responses, or antiretroviral therapy. This high-level variance has
      led to a wide range in observed fitness and virulence, across strains of HIV-1.
      The HIV-1 pol replication capacity assay (pol RC) measures features of viral
      fitness, associates with elevated CD4+ T-cell counts, yet is not strongly
      associated with HIV-1 RNA levels. The biological basis for elevated CD4+ T-cell
      counts among those carrying a virus of low pol RC may be because of lowered virus
      infectivity, or restricted tissue replication.

PMID- 16091247
TI  - HIV-1 infection of the female reproductive tract.
AB  - The human immunodeficiency virus type 1 (HIV-1) infects cells within mucosal
      tissues, including those of the female reproductive tract (FRT). The mechanism of
      viral transmission within the FRT and the mode of viral spread to the periphery
      are not completely understood. We performed phenotypical analyses and infectivity
      studies of primary FRT cells to identify potential targets of infection within
      the FRT. Our findings indicate that expression of HIV-1 receptors and coreceptors
      in the FRT varies as a function of menstrual-cycle stage, suggesting that sex
      hormone levels may influence a woman's susceptibility to infection by HIV-1.
      Moreover, HIV-1 strains that utilize the CXCR4 chemokine receptor for infectivity
      are able to undergo reverse transcription, integration, viral DNA transcription,
      and viral release, whereas viral strains that utilize CCR5 do not undergo these
      early replicative events, and are only released unmodified from these cells. This
      indicates that several mechanisms for viral infection and transmission are
      present throughout the FRT.

PMID- 16091248
TI  - The effects of HIV protease inhibitors on carbohydrate and lipid metabolism.
AB  - Since the introduction of HIV protease inhibitors (PIs), disorders of glucose and
      lipid metabolism have emerged. In dissecting out the direct effect on lipid and
      glucose metabolism, it has become apparent that individual PIs have different
      effects on metabolism. Some PIs such as indinavir acutely induce insulin
      resistance. PIs have also been shown to cause other disorders of glucose
      metabolism, including impairment of insulin secretion and increased endogenous
      glucose production. Individual PIs also have different effects on lipid
      metabolism. Ritonavir predominantly increases triglyceride and very low-density
      lipoprotein cholesterol levels. Limited studies in HIV-negative volunteers
      suggest that several of the PIs do not increase low-density lipoprotein
      cholesterol levels. This review examines the direct effects of PIs on glucose and
      lipid metabolism by assessing prospective studies of HIV-infected and healthy
      normal volunteers, and in vitro studies.

PMID- 16091249
TI  - Primary human immunodeficiency virus type 1 infection.
AB  - Primary human immunodeficiency virus type 1 (HIV-1) infection represents the
      initial stage of disease that immediately follows viral entry into the body.
      Primary infection is frequently accompanied by an acute retroviral syndrome with
      associated high levels of plasma HIV-1 RNA and the development of host immune
      responses. The identification of subjects during this period requires a high
      index of suspicion and an understanding of how to make the diagnosis, as standard
      HIV-1 antibody tests can initially be negative. Identifying these people provides
      a unique opportunity for early counseling to reduce further transmission,
      facilitates entry into care, and allows for further study of the
      immunopathogenesis of disease and the potential role of early antiretroviral
      therapy.

PMID- 16091250
TI  - Therapeutic drug monitoring: pharmacologic considerations for antiretroviral
      drugs.
AB  - Therapeutic drug monitoring (TDM) is the process by which a patient's dosing
      regimen is guided by repeated measures of plasma drug concentrations. An enormous
      challenge with regard to TDM of antiretroviral drugs (ARV) is that the
      concentration goals can be moving targets. Well-designed prospective studies
      demonstrating that prospectively altering ARV doses based on TDM leads to
      virologic success and increased tolerability are needed. Nevertheless, there are
      specific clinical instances where this experimental intervention should be
      considered to potentially reduce toxicity and improve therapeutic outcomes.

PMID- 16091251
TI  - Coronary heart disease in HIV-infected patients.
AB  - Increased risk of coronary heart disease has emerged as a long-term concern among
      HIV-infected patients receiving antiretroviral therapy. HIV-infected patients may
      have modifiable risk factors for heart disease that are associated with HIV
      itself, antiretroviral therapy, or factors unrelated to HIV. Dyslipidemia,
      insulin resistance, and diabetes mellitus are often multifactorial in origin.
      Patients with lipodystrophy frequently have a constellation of metabolic changes
      that may predispose them to accelerated atherosclerosis. There is also concern
      about contributions of chronic inflammation and prothrombotic tendencies in the
      pathogenesis of coronary heart disease in the HIV-infected population. Several
      epidemiological studies support an increased relative risk of myocardial
      infarction in HIV-infected patients on highly active antiretroviral therapy.
      Although absolute risk appears low in the short term, patients may accrue
      significant risk over time. Clinicians are advised to assess coronary heart
      disease risk in HIV-infected patients and to intervene to reduce the impact of
      modifiable risk factors.

PMID- 16091252
TI  - Body shape, lipid, and cardiovascular complications of HIV therapy.
AB  - Metabolic complications of HIV therapy have emerged as a vexing problem for
      individuals living with HIV infection and their clinicians. These adverse effects
      threaten health and quality of life as well as adherence to HIV treatment. Among
      the most common metabolic complications confronting clinicians are body shape
      changes and dyslipidemia. The pathogenesis of these disorders remains elusive,
      challenging the development of treatment strategies particularly for fat
      redistribution. Switching from metabolically offensive antiretrovirals has
      yielded improvements in both body shape and dyslipidemia. In addition,
      therapeutic approaches that have been developed for the treatment of dyslipidemia
      in HIV-uninfected patients, can with important caveats be applied to HIV therapy
      associated lipid disorders. Aggressive assessment of cardiovascular disease risk
      and intervention is likely to reduce the incidence of cardiovascular disorders in
      HIV-infected patients. Development of antiretrovirals with fewer metabolic
      adverse effects will reduce the incidence of these and similar disorders during
      HIV therapy.

PMID- 16091253
TI  - Approach to the treatment-experienced patient.
AB  - Failure of antiretroviral therapy can occur for a variety of reasons, but is
      often caused by or accompanied by drug resistance, which increases with continued
      time on nonsuppressive, failing regimens. Response to early virologic failure on
      an initial regimen may be associated with minimal or no resistance and can
      sometimes be managed simply by reinforcing adherence or by intensifying therapy.
      Resistance testing is an important tool for managing patients who are failing
      therapy; it should be used in most cases to guide selection of the next regimen.
      For patients with extensive treatment experience and drug resistance, there are a
      variety of approaches that have been suggested when fully suppressive options are
      not available. Clinicians caring for such patients must balance the benefit of
      slower progression associated with continued therapy against the risk of
      increasing drug resistance and loss of future treatment options.

PMID- 16091254
TI  - Immune-based therapies: an adjunct to antiretroviral treatment.
AB  - Combination antiretroviral therapy potently suppresses HIV replication, but does
      not eradicate the infection. Drug resistance and long-term toxicities limit its
      use. The recovery of general immune function is often not complete. Immune-based
      therapies have the potential to boost HIV-specific immunity and reduce the need
      for antiretroviral drugs, and to promote general immune competence in situations
      in which antiretroviral treatment alone is inadequate. Strategies to reduce the
      immunopathogenic consequences of HIV infection with immunomodulating therapies
      are conceivable. Ultimately, eradication of the infection will require methods to
      target the latent memory T-cell reservoir of virus.

PMID- 16091255
TI  - HIV antiretroviral therapy in resource-limited settings: experiences from Haiti.
AB  - An unprecedented international effort to expand high activity antiretroviral
      therapy (HAART) to resource-poor nations has been launched. The World Health
      Organization (WHO) has created antiretroviral (ARV) treatment guidelines adapted
      to resource-poor settings. The first-line regimen is two nucleoside reverse
      transcriptase inhibitors (NsRTIs) and one nonnucleoside reverse transcriptase
      inhibitor (NNRTI). Therapy is initiated by clinical staging and CD4 T-cell counts
      when available. Adherence is the responsibility of health care workers. The use
      of ARV therapy in resource-poor settings faces several challenges, including the
      poverty of patients, political and social upheavals and violence, social stigma
      associated with HIV/AIDS, unreliable pharmacy systems, tuberculosis, and lack of
      trained health care workers. Using our experience in Haiti, we describe how we
      have addressed these challenges with the goal of increasing access to care for
      the poor with HIV/AIDS.

PMID- 16091256
TI  - HIV-associated renal disorders: recent insights into pathogenesis and treatment.
AB  - Renal electrolyte disorders, acute renal failure, and a variety of chronic renal
      diseases are common in HIV-infected patients. Glomerular disorders include IgA
      nephropathy, cryoglobulinemia, amyloidosis, and a lupus-like immune complex
      glomerulopathy. The most attention has been focused on collapsing glomerulopathy
      associated with nephrotic syndrome and progressive renal failure, which appears
      to be unique for patients with HIV/AIDS, called HIV-associated nephropathy
      (HIVAN), and it occurs predominantly in African American patients. Investigations
      in humans and in a transgenic mouse model reveal direct infection of renal
      epithelial cells by HIV and toxic cellular and immunologic processes mediated by
      HIV glycoproteins as the principal pathophysiology of HIVAN. Highly active
      antiretroviral treatment may be associated with an improved renal outcome and
      even reversal of kidney disease in some patients. Treatment with angiotensin
      converting enzyme inhibitors may avert progression of HIVAN to end-stage kidney
      disease and result in superior patient and kidney survival as compared with
      untreated patients.

PMID- 16091257
TI  - HIV-associated tuberculosis and cryptococcosis in resource-limited settings.
AB  - Tuberculosis (TB) and cryptococcosis are common infectious complications in HIV
      in resource-limited settings and contribute substantial morbidity and mortality.
      The increasing access to highly active antiretroviral treatment (HAART) has
      invited numerous challenges such as timing of HAART, cotreatment (drug dosages
      and interaction), immune reconstitution syndromes, and withdrawal of
      chemoprophylaxis. Numerous small studies propose the feasibility of concomitant
      TB/HIV treatment that needs to be confirmed in large, randomized trials.
      Treatment of acute cryptococcocal meningo-encephalitis with amphoterecin B is
      fraught with logistic problems in resource-limited settings. An effective safe
      dose of fluconazole as monotherapy needs to be determined in phase II studies.
      Current management guidelines extrapolated from developed countries may not
      necessarily apply and need validation in resource-limited settings.

PMID- 16091258
TI  - Managing hepatitis B coinfection in HIV-infected patients.
AB  - Since viral hepatitis is one of the most common causes of morbidity and mortality
      in HIV, it is critical to recognize and treat these patients appropriately.
      Hepatitis B infection is particularly difficult to manage as it changes with
      shifts in immune status. Inactive infection may flare up with restoration of CD4
      cell count. In addition, many drugs used to treat HIV are also active against
      hepatitis B. Thus, patients may require therapy for both diseases or only for
      hepatitis B. The practicing physician must be aware of which drug to use with
      antiretrovirals and which can be used for hepatitis B alone. Current therapies
      for HIV that have hepatitis B activity include lamivudine, emtricitabine, and
      tenofovir. Therapies for hepatitis B without HIV activity are adefovir and
      entecavir. The major advances in the past year include emerging data on
      epidemiology, occult infection, genotypes, and newer therapies. Long-term
      management of hepatitis B includes monitoring for hepatocellular carcinoma. Two
      recent consensus conferences have provided excellent reviews of management of
      coinfection .

PMID- 16091259
TI  - Plastic surgical approaches for HIV-associated lipoatrophy.
AB  - Prolonged antiretroviral therapy, particularly with thymidine analogue-based
      regimens, may lead to generalized lipoatrophy. The facial changes associated with
      lipoatrophy are highly stigmatizing, affecting quality of life and decisions
      around therapy. Changes in antiretrovirals to thymindine-sparing regimens may
      lead to gradual fat recovery but, even over several years, may not result in
      impressive restoration of appearance. The need for a rapid and effective panacea
      for facial changes has led to investigation of a range of cosmetic treatments to
      enhance facial appearance. Surgical fillers, which may be either permanent or
      biodegradable, are the mainstay of cosmetic management. These treatments not only
      lead to improved physical appearance but also may reduce social anxiety and
      depression.

PMID- 16091260
TI  - Lipids, metabolic syndrome, and risk factors for future cardiovascular disease
      among HIV-infected patients.
AB  - The availability of potent combination antiretroviral therapy has changed the
      long-term prognosis for people living with HIV/AIDS. There is increasing concern,
      however, about the effect of HIV therapy on lipid disorders and subsequent
      development of coronary artery disease. Virtually all classes of antiretroviral
      drugs have been associated with some aspect of atherogenic changes in the lipid
      profiles. This article reviews the current literature on HIV-associated
      dyslipidemias and the metabolic syndrome, their potential effect on future
      coronary heart disease, and reviews strategies for management.

PMID- 16091261
TI  - Human papillomavirus-related cervical and anal disease in HIV-infected
      individuals in the era of highly active antiretroviral therapy.
AB  - HIV-infected men who have sex with men remain at high risk of developing anal
      cancer despite the widespread use of highly active antiretroviral therapy
      (HAART). In HIV-infected women, however, there is some evidence that HAART may be
      associated with regression of human papillomavirus (HPV)-related cervical
      disease. So far, epidemiologic data provided by cancer registries have shown no
      reduction in the incidence of cervical and anal cancer in patients with HIV
      infection since the initiation of HAART in 1996. Recent data suggest that HPV
      infection occurs in the anal canal of immunocompromised patients, as an
      opportunistic infection, in the absence of receptive anal intercourse. Taken
      together, these lines of evidence support the need for developing anal and
      cervical cancer screening programs for patients with HIV, whether untreated or on
      HAART.

PMID- 16091262
TI  - Non-AIDS-defining cancers and HIV infection.
AB  - With fewer patients now succumbing to infectious complications of AIDS, other HIV
      related morbidities, such as malignancies, have become increasingly important.
      Apart from Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer, which
      are considered as AIDS-defining, several additional cancers, referred to as non
      AIDS-defining cancers, are also statistically increased in HIV-infected persons.
      These include Hodgkin's disease, anal carcinoma, lung cancer, nonmelanomatous
      skin cancer, and testicular germ cell tumors, among others. However, the types of
      cancer observed at an increased frequency and the relative risks reported vary
      widely among studies. Although immunosuppression is consistently associated with
      an increased risk of AIDS-related malignancies, the role of immunosuppression in
      the pathogenesis of non-AIDS- defining cancers is controversial. Although data
      regarding the optimal management of these cancers are lacking, current studies
      suggest that patients with HIV-associated malignancies should be treated with
      similar approaches to those of their counterparts in the general population.

PMID- 16091263
TI  - State-dependent thinking: a comparison of waking and dreaming thought.
AB  - Thinking is known to be state dependent but a systematic study of how thinking in
      dreams differs from thinking while awake has not been done. The study consisted
      of analyzing the dream reports of 26 subjects who, in addition to providing dream
      reports also provided answers to questions about their thinking within the dream.
      Our hypothesis was that thinking in dreams is not monolithic but has two distinct
      components, one that is similar to wake-state cognition, and another that is
      fundamentally different. We found that cognition within a dream scenario was
      similar to that of wake-state cognition, but that thinking about the scenario
      itself was deficient and very different than wake-state thinking.

PMID- 16091264
TI  - On the inference of personal authorship: enhancing experienced agency by priming
      effect information.
AB  - Three experiments examined whether the mere priming of potential action effects
      enhances people's feeling of causing these effects when they occur. In a computer
      task, participants and the computer independently moved a rapidly moving square
      on a display. Participants had to press a key, thereby stopping the movement.
      However, the participant or the computer could have caused the square to stop on
      the observed position, and accordingly, the stopped position of the square could
      be conceived of as the potential effect resulting from participants' action of
      pressing the stop key. The location of this position was primed or not just
      before participants had to stop the movement. Results showed that (subliminal as
      well as supraliminal) priming of the position enhanced experienced authorship of
      stopping the square. Additional experimentation demonstrated that this priming of
      agency was not mediated by the goal or intention to produce the effect.

PMID- 16091265
TI  - Does priming with awareness reflect explicit contamination? An approach with a
      response-time measure in word-stem completion.
AB  - The present experiment investigates the involvement of awareness in functional
      dissociations between explicit and implicit tests. In the explicit condition,
      participants attempted to recall lexically or semantically studied words using
      word stems. In the implicit condition, they were instructed to complete each stem
      with the first word which came to mind. Subjective awareness was subsequently
      measured on an item-by-item basis. As voluntary retrieval strategies are known to
      be time consuming, the time taken to complete each stem was recorded. In the
      explicit task, semantically studied words were associated with higher levels of
      recall and faster response times than lexically studied words. By contrast, in
      the implicit task, these effects failed to reach significance, although deep
      encoding made the contents of memory more accessible to awareness. As expected,
      performance was slower in the explicit than in the implicit task, but in the
      latter condition, times to produce old words with and without awareness were
      comparable, and both of these responses were produced more quickly than control
      words. This finding suggests that although participants may become aware in
      implicit paradigms, they do not adopt voluntary retrieval strategies.

PMID- 16091266
TI  - The effect of unconscious priming on temporal production.
AB  - We examined the effects of unconscious priming on temporal-interval production.
      In Experiment 1, participants were instructed to keep visual displays on a screen
      for 2500 ms intervals. Half of the displays were repeated across blocks
      throughout the entire experiment, and the others were newly generated from trial
      to trial. The displays consisted of patterns so complex that the participants
      could not intentionally memorize them. The results showed that significantly more
      time elapsed for old displays than for new displays before participants indicated
      that a 2500 ms interval had elapsed. Experiment 2 replicated this effect and
      excluded an alternative account based on perceived pattern complexity. The effect
      of repetitive presentation was obtained despite the fact the participants did not
      recognize the repetition, suggesting that unconscious priming increased temporal
      production. These results suggest that time perception is affected by an
      unconscious process.

PMID- 16091267
TI  - The ontology of neglect.
AB  - As shown by neuroscientific evidence, neglect may occur without elementary
      sensorimotor impairments. The deficit is to be found at a higher, more abstract
      level of representation, which prevents the patient not only from seeing, but
      from conceiving the contralesional space. By analysing a series of
      neuropsychological results, in this paper we suggest a crucial role of time for
      the construction of a world: on this basis, we try to explain how it is possible
      that half the ontology gets lost. The analysis of the ontological implication of
      neglect will allow us to shed light on manifestations of the pathology apparently
      disconnected.

PMID- 16091268
TI  - Are strategy shifts caused by data-driven processes or by voluntary processes?
AB  - The present research investigates the role of voluntary, conscious processing in
      strategy change. In 2 experiments, we address whether the switch to a new
      strategy is the result of data-driven, automatic processes or of voluntary
      processes. Experiment 1 demonstrates that participants performing an alphabet
      verification task are able to (a) transfer a newly adopted strategy to dissimilar
      information never encountered before, (b) verbally describe the task regularity
      that allows for the generation and application of the new strategy immediately
      after the strategy was adopted. Using the same experimental task, Experiment 2
      shows that participants, and (c) decide against adopting a new strategy when the
      available evidence suggests that the new strategy cannot be used for the entire
      range of problems encountered. Overall, the obtained results support the view
      that strategy change is mediated by voluntary controlled processing. They do not
      support the view that strategy change is an inevitable, automatic consequence of
      task practice. The present research thus highlights a potential function of
      conscious human processing.

PMID- 16091269
TI  - Conscious recollection in autobiographical memory: an investigation in
      schizophrenia.
AB  - Whether or not conscious recollection in autobiographical memory is affected in
      schizophrenia is unknown. The aim of this study was to address this issue using
      an experiential approach. An autobiographical memory enquiry was used in
      combination with the Remember/Know procedure. Twenty-two patients with
      schizophrenia and 22 normal subjects were asked to recall specific
      autobiographical memories from four lifetime periods and to indicate the
      subjective states of awareness associated with the recall of what happened, when
      and where. They gave Remember, Know or Guess responses according to whether they
      recalled these aspects of the event on the basis of conscious recollection,
      simply knowing, or guessing. Results showed that the frequency and consistency of
      Remember responses was significantly lower in patients than in comparison
      subjects. In contrast, the frequency of Know responses was not significantly
      different, whereas the frequency of patients' Guess responses was significantly
      enhanced. It is concluded that the frequency and consistency of conscious
      recollection in autobiographical memory is reduced in patients with
      schizophrenia.

PMID- 16091270
TI  - Strength of visual percept generated by famous faces perceived without awareness:
      effects of affective valence, response latency, and visual field.
AB  - Participants who were unable to detect familiarity from masked 17 ms faces (Stone
      and Valentine, 2004 and Stone and Valentine, in press-b) did report a vague,
      partial visual percept. Two experiments investigated the relative strength of the
      visual percept generated by famous and unfamiliar faces, using masked 17 ms
      exposure. Each trial presented simultaneously a famous and an unfamiliar face,
      one face in LVF and the other in RVF. In one task, participants responded
      according to which of the faces generated the stronger visual percept, and in the
      other task, they attempted an explicit familiarity decision. The relative
      strength of the visual percept of the famous face compared to the unfamiliar face
      was moderated by response latency and participants' attitude towards the famous
      person. There was also an interaction of visual field with response latency,
      suggesting that the right hemisphere can generate a visual percept
      differentiating famous from unfamiliar faces more rapidly than the left
      hemisphere. Participants were at chance in the explicit familiarity decision,
      confirming the absence of awareness of facial familiarity.

PMID- 16091271
TI  - Functional consequences of perceiving facial expressions of emotion without
      awareness.
AB  - A substantial body of research has established that even when we are not
      consciously aware of the faces of others we are nevertheless sensitive to, and
      impacted by their facial expression. In this paper, we consider this body of
      research from a new perspective by examining the functions of unconscious
      perception revealed by these studies. A consideration of the literature from this
      perspective highlights that existing research methods are limited when it comes
      to revealing possible functions of unconscious perception. The critical
      shortcoming is that in all of the methods, the perceived facial expression
      remains outside of awareness. This is a problem because there are good reasons to
      believe that one important function of unconsciously perceived negative faces is
      to attract attention so that they are consciously perceived; such conscious
      perception, however, is never allowed with existing methodologies. We discuss
      recent studies of emotional face perception under conditions of visual search
      that address this issue directly. Further, we suggest that methodologies that do
      not examine cognitive processes as they occur in more natural settings may result
      in fundamental misunderstandings of human cognition.

PMID- 16091272
TI  - Unconscious processing of multiple nonadjacent letters in visually masked words.
AB  - The claim that visually masked, unidentifiable ("subliminal") words are analyzed
      at the level of whole word meaning has been challenged by recent findings
      indicating that instead, analysis occurs mainly at the subword level. The present
      experiments examined possible limits on subword analysis. Experiment 1 obtained
      semantic priming from pleasant- and unpleasant-meaning subliminal words in which
      no individual letter contained diagnostic information about a word's evaluative
      valence; thus analysis must operate on information more complex than that
      contained in individual letters. Experiments 2 and 3 showed that analysis must
      operate on information more complex than that represented by individual bigrams
      (adjacent letters) or trigrams (three consecutive letters). These findings
      suggest that while subliminal priming is driven by subword analysis, the
      effective units of analysis are distributed widely across at least short (four-
      and five-letter) words.

PMID- 16091273
TI  - Fantasy proneness, but not self-reported trauma is related to DRM performance of
      women reporting recovered memories of childhood sexual abuse.
AB  - Extending a strategy previously used by , we administered a neutral and a trauma
      related version of the Deese-Roediger-McDermott paradigm to a sample of women
      reporting recovered (n=23) or repressed memories (n=16) of childhood sexual abuse
      (CSA), women reporting having always remembered their abuse (n=55), and women
      reporting no history of abuse (n=20). We found that individuals reporting
      recovered memories of CSA are more prone than other participants to falsely
      recalling and recognizing neutral words that were never presented. Moreover, our
      study is the first to show that this finding even held when trauma-related
      material was involved. Correlational analyses revealed that fantasy proneness,
      but not self-reported traumatic experiences and dissociative symptoms were
      related to false recall and false recognition.

PMID- 16091274
TI  - Split-brain reveals separate but equal self-recognition in the two cerebral
      hemispheres.
AB  - To assess the ability of the disconnected cerebral hemispheres to recognize
      images of the self, a split-brain patient (an individual who underwent complete
      cerebral commissurotomy to relieve intractable epilepsy) was tested using morphed
      self-face images presented to one visual hemifield (projecting to one hemisphere)
      at a time while making "self/other" judgments. The performance of the right and
      left hemispheres of this patient as assessed by a signal detection method was not
      significantly different, though a measure of bias did reveal hemispheric
      differences. The right and left hemispheres of this patient independently and
      equally possessed the ability to self-recognize, but only the right hemisphere
      could successfully recognize familiar others. This supports a modular concept of
      self-recognition and other-recognition, separately present in each cerebral
      hemisphere.

PMID- 16091277
TI  - Selective transport of ions and molecules across layer-by-layer assembled
      membranes of polyelectrolytes, p-sulfonato-calix[n]arenes and Prussian Blue-type
      complex salts.
AB  - Our recent studies in the field of ultrathin membranes prepared upon layer-by
      layer assembly of various polyionic compounds such as polyelectrolytes,
      calixarenes and polyelectrolytes, and metal hexacyanoferrate salts such as
      Prussian Blue are reviewed. It is demonstrated that polyelectrolyte multilayers
      can be used (a) as nanofiltration and reverse osmosis membranes suitable for
      water softening and seawater desalination and (b) as molecular sieves and ion
      sieves for size-selective separation of neutral and charged aromatic compounds.
      Furthermore, hybrid membranes of p-sulfonato-calixarenes and cationic
      polyelectrolytes showing specific host-guest interactions with permeating ions
      are described. The membranes exhibit high selectivities for distinct metal ions.
      Finally, it is demonstrated that purely inorganic membranes of Prussian Blue (PB)
      and analogues can be prepared upon multiple sequential adsorption of transition
      metal cations and hexacyanoferrate anions. Due to the porous lattice of PB, the
      membranes are useful as ion filters able to separate cesium from sodium ions, for
      example.

PMID- 16091278
TI  - Sensitivity comparison of real-time PCR probe designs on a model DNA plasmid.
AB  - We investigated three probe design strategies used in quantitative polymerase
      chain reaction (PCR) for sensitivity in detection of the PCR amplicon. A plasmid
      with a 120-bp insert served as the DNA template. The probes were TaqMan,
      conventional molecular beacon (MB), and shared-stem molecular beacon (ATssMB and
      GCssMB). A shared-stem beacon probe combines the properties of a TaqMan probe and
      a conventional molecular beacon. It was found that the overall sensitivities for
      the four PCR probes are in the order of MB>ATssMB>GCssMB>TaqMan. The fluorescence
      quantum yield measurements indicate that incomplete or partial enzymatic cleavage
      catalyzed by Taq polymerase is the likely cause of the low sensitivities of two
      shared-stem beacons when compared with the conventional beacon probe. A high
      fluorescence background associated with the current TaqMan probe sequence
      contributes to the relatively low detection sensitivity and signal-to-background
      ratio. The study points out that the nucleotide environment surrounding the
      reporting fluorophore can strongly affect the probe performance in real-time PCR.

PMID- 16091279
TI  - An improved colorimetric method for quantitation of heme using
      tetramethylbenzidine as substrate.

PMID- 16091280
TI  - Directional surface plasmon-coupled emission: application for an immunoassay in
      whole blood.
AB  - We present a new approach for performing fluorescence immunoassay in whole blood
      using fluorescently labeled anti-rabbit immunoglobulin G (IgG) on a silver
      surface. This approach, which is based on surface plasmon-coupled emission
      (SPCE), provides increased sensitivity and substantial background reduction due
      to exclusive selection of the signal from the fluorophores located near a
      bioaffinity surface. This article describes the effect of an optically dense
      sample matrix, namely human whole blood and serum, on the intensity of the SPCE.
      An antigen (rabbit IgG) was adsorbed to a slide covered with a thin silver metal
      layer, and the SPCE signal from the fluorophore-labeled anti-rabbit antibody,
      binding to the immobilized antigen, was detected. The effect of the sample matrix
      (buffer, human serum, or human whole blood) on the end-point immunoassay SPCE
      signal was studied. It was demonstrated that the kinetics of binding could be
      monitored directly in whole blood or serum. The results showed that human serum
      and human whole blood attenuate the SPCE end-point signal and the immunoassay
      kinetic signal only approximately two- and threefold, respectively, as compared
      with buffer, resulting in signals that are easily detectable even in whole blood.
      The high optical absorption of the hemoglobin can be tolerated because only
      fluorophores within a couple of hundred nanometers from the metallic film
      contribute to SPCE. Excited fluorophores outside the 200-nm layer do not
      contribute to SPCE, and their free space emission is not transmitted through the
      opaque metallic film into the glass substrate. We believe that SPCE has the
      potential of becoming a powerful approach for performing immunoassays based on
      surface-bound analytes or antibodies for many biomarkers directly in dense
      samples such as whole blood with no need for washing steps.

PMID- 16091281
TI  - Onset of oxidative damage in alpha-crystallin by radical probe mass spectrometry.
AB  - The early onset oxidative damage within segments of the protein alpha-crystallin
      is examined by radical probe mass spectrometry by its treatment with reactive
      oxygen species under low-, moderate-, and high-oxidizing conditions. Five regions
      comprising the first 11 residues of the N-termini of the A and B subunits (A/B:1
      11), central domains from each subunit B:57-69 and A:104-112, and a C-terminal
      segment of the A subunit A:120-145 were found to be the initial sites of
      oxidation. The susceptibility of each segment to oxidation and oxidative damage
      is investigated by subjecting the intact protein to different oxidation
      conditions within the ion source of an electrospray ionization mass spectrometer.
      LC-MS of the oxidized protein digests enables the sites and levels of oxidation
      to be monitored. The onset of oxidative damage and the levels of oxidation
      observed before damage occurs differ across the protein surface. The regions
      comprising residues A/B:1-11 and A:104-112 are shown to be more susceptible to
      oxidative damage than those comprising residues B:57-69 and A:120-145. The
      results are discussed in the context of available experimental and homology
      modeled theoretical structures for the subunits of alpha-crystallin.

PMID- 16091282
TI  - A method for the isolation of covalent DNA-protein crosslinks suitable for
      proteomics analysis.
AB  - The covalent crosslinking of protein to DNA is a form of DNA damage induced by a
      number of commonly encountered agents, including metals, aldehydes, and radiation
      as well as chemotherapeutic drugs. DNA-protein crosslinks (DPCs) are potentially
      bulky and helix distorting and have the potential to block the progression of
      translocating protein complexes. To fully understand the induction and repair of
      these lesions, it will be important to identify the crosslinked proteins
      involved. To take advantage of dramatic improvements in instrument sensitivity
      that have facilitated the identification of proteins by proteomic approaches,
      improved methods are required for isolation of DPCs. This article describes a
      novel method for the isolation of DPCs from mammalian cells that uses chaotropic
      agents to isolate genomic DNA and stringently remove noncrosslinked proteins
      followed by DNase I digestion to release covalently crosslinked proteins. This
      method generates high-quality protein samples in sufficient quantities for
      analysis by mass spectrometry. In addition, the article presents a modified form
      of this method that also makes use of chaotropic agents for promoting the
      adsorption of DNA (with crosslinked proteins) to silica fines, markedly reducing
      the DPC isolation time and cost. These approaches were applied to radiation- and
      camptothecin-induced DPCs.

PMID- 16091283
TI  - Direct amperometric determination of lipase activity.

PMID- 16091284
TI  - A biochemical analysis of topoisomerase II alpha and beta kinase activity found
      in HIV-1 infected cells and virus.
AB  - Human topoisomerase II plays a crucial role in DNA replication and repair. It
      exists in two isoforms: topoisomerase II alpha (alpha) and topoisomerase II beta
      (beta). The alpha isoform is localized predominantly in the nucleus, while the
      beta isoform exhibits a reticular pattern of distribution both in the cytosol and
      in the nucleus. We show that both isoforms of topoisomerase II are phosphorylated
      in HIV infected cells and also by purified viral lysate. An analysis of the
      phosphorylation of topoisomerase II isoforms showed that extracts of HIV infected
      cells at 8 and 32 h. post-infection (p.i.) contain maximal phosphorylated
      topoisomerase II alpha, whereas infected cell extracts at 4 and 64 h p.i. contain
      maximum levels of phosphorylated topoisomerase II beta. In concurrent to
      phosphorylated topoisomerase II isoforms, we have also observed increased
      topoisomerase II alpha kinase activity after 8h p.i and topoisomerase beta kinase
      activity at 4 and 64 h p.i. These findings suggest that both topoisomerase II
      alpha and beta kinase activities play an important role in early as well as late
      stages of HIV-1 replication. Further analysis of purified virus showed that HIV-1
      virion contained topoisomerase II isoform-specific kinase activities, which were
      partially isolated. One of the kinase activities of higher hydrophobicity can
      phosphorylate both topoisomerase II alpha and beta, while lower hydrophobic
      kinase could predominantly phosphorylate topoisomerase II alpha. The
      phosphorylation status was correlated with catalytic activity of the enzyme.
      Western blot analysis using phosphoamino-specific antibodies shows that both the
      kinase activities catalyze the phosphorylation at serine residues of
      topoisomerase II alpha and beta. The catalytic inhibitions by serine kinase
      inhibitors further suggest that the alpha and beta kinase activities associated
      with virus are distinctly different.

PMID- 16091285
TI  - Effect of D-amino acids at Asp23 and Ser26 residues on the conformational
      preference of Abeta20-29 peptides.
AB  - The effects of d-amino acids at Asp(23) and Ser(26) residues on the
      conformational preference of beta-amyloid (Abeta) peptide fragment (Abeta(20-29))
      have been studied using different spectroscopic techniques, namely vibrational
      circular dichroism (VCD), vibrational absorption, and electronic circular
      dichroism. To study the structure of the Abeta(20-29), [d-Asp(23)]Abeta(20-29),
      and [d-Ser(26)]Abeta(20-29) peptides under different conditions, the spectra were
      measured in 10mM acetate buffer (pH 3) and in 2,2,2-trifluoroethanol (TFE). The
      spectroscopic results indicated that at pH 3, Abeta(20-29) peptide takes random
      coil with beta-turn structure, while [d-Ser(26)]Abeta(20-29) peptide adopts
      significant amount of polyproline II (PPII) type structure along with beta-turn
      contribution and d-Asp-substituted peptide ([d-Asp(23)]Abeta(20-29)) adopts
      predominantly PPII type structure. The increased propensity for PPII conformation
      upon d-amino acid substitution, in acidic medium, has important biological
      implications. In TFE, Abeta(20-29), [d-Asp(23)]Abeta(20-29), and [d
      Ser(26)]Abeta(20-29) peptides adopt 3(10)-helix, alpha-helix, and random coil
      with some beta-turn structures, respectively. The VCD data obtained for the Abeta
      peptide films suggested that the secondary structures for the peptide films are
      not the same as those for corresponding solution and are also different among the
      Abeta peptides studied here. This observation suggests that dehydration can have
      a significant influence on the structural preferences of these peptides.

PMID- 16091286
TI  - Transformation of mouse fibroblasts alters the induction pattern of type I IFNs
      after virus infection.
AB  - Type I interferons (IFNs) have been shown to be involved in many immune defence
      and inflammatory responses. We here show that IFN-beta plays an absolute
      essential role in the efficient induction of all type I IFNs after infection of
      primary embryonic as well as primary adult fibroblasts with Sendai virus. In
      contrast, after immortalization of such fibroblasts with SV40 large T antigen,
      IFN-alpha4 can be induced independently of IFN-beta. However, efficient secretion
      of type I IFNs even in immortalized fibroblasts is only found when the complete
      signalling loop is induced by IFN-beta.

PMID- 16091288
TI  - Mercury and selenium concentrations in hair samples of women in fertile age from
      Amazon riverside communities.
AB  - The aim of the present study was to evaluate mercury and selenium concentrations
      in hair samples of reproductive age women from riverside communities of the
      Tapajos River basin. We studied 19 pregnant and 21 non-pregnant women, 13 to 45
      years old, living in the region for at least 2 years, and having a diet rich in
      fish. The analysis of Se and total Hg were performed in the Instituto de
      Pesquisas Energeticas e Nucleares (IPEN, Sao Paulo, Brazil) by using a Varian
      AA220-FS atomic absorption spectrometer with a flow injection system. There were
      no differences between the two groups - pregnant and non-pregnant -- concerning
      age (23.80 +/- 6.92 and 26.60 +/- 9.60 years old, respectively) and residential
      time (20.21 +/- 8.30 and 22.20 +/- 10.90 years, respectively). The geometric
      means and ranges for total Hg concentration were similar (p > 0.05): 8.25
      microg/g (1.51-19.43) in pregnant and 9.39 microg/g (5.25-21.00) in non-pregnant
      women, respectively. Total Hg concentrations were also similar in different
      gestational stages. However, there was a significant difference between the two
      groups (p < 0.05, Student t test) in relation to Se concentration: 0.61 microg/g
      (0.40-2.33) in pregnant and 2.46 microg/g (0.92-5.74) in non-pregnant women,
      respectively. We concluded that Hg exposure levels in reproductive age women were
      only slightly higher than a provisional tolerable weekly intake of MeHg would
      provide, that Hg concentration in maternal hair samples was independent of
      gestational age, and that low Se concentration in pregnant women indicates high
      mineral consumption by fetal organism to satisfy their metabolic requirements
      raised during pregnancy, including as a protective mechanism for Hg cytotoxic
      effects.

PMID- 16091289
TI  - Occurrence of antibiotics in wastewater treatment facilities in Wisconsin, USA.
AB  - Samples from several wastewater treatment facilities in Wisconsin were screened
      for the presence of 21 antibiotic compounds. These facilities spanned a range of
      community size served (average daily flow from 0.0212 to 23.6 million
      gallons/day), secondary treatment processes, geographic locations across the
      state, and they discharged the treated effluents to both surface and ground
      waters (for ground water after a soil passage). A total of six antibiotic
      compounds were detected (1-5 compounds per site), including two sulfonamides
      (sulfamethazine, sulfamethoxazole), one tetracycline (tetracycline),
      fluoroquinolone (ciprofloxacin), macrolide (erythromycin-H(2)O) and trimethoprim.
      The frequency of detection of antibiotics was in the following order:
      tetracycline and trimethoprim (80%)>sulfamethoxazole (70%)>erythromycin-H(2)O
      (45%)>ciprofloxacin (40%)>sulfamethazine (10%). However, the soluble
      concentrations were in the parts-per-billion (ppb) range (<or=1.3 microg/L), and
      importantly were unaffected by the size of the wastewater treatment facility. The
      concentrations detected were within an order of magnitude of those reported for
      similar systems in Europe and Canada: they were within a factor of two in
      comparison to those reported for Canada but generally lower relative to those
      measured in wastewater systems in Europe. Only sulfamethoxazole and tetracycline
      were detected in groundwater monitoring wells adjacent to the treatment systems.
      Future intensive wastewater monitoring programs in Wisconsin may be limited to
      the six antibiotic compounds detected in this study.

PMID- 16091290
TI  - Efficiency of the activated carbon filtration in the natural organic matter
      removal.
AB  - The removal and transformation of natural organic matter were monitored in the
      different stages of the drinking water treatment train. Several methods to
      measure the quantity and quality of organic matter were used. The full-scale
      treatment sequence consisted of coagulation, flocculation, clarification by
      flotation, disinfection with chlorine dioxide, activated carbon filtration and
      post-chlorination. High-performance size-exclusion chromatography separation was
      used to determine the changes in the humic substances content during the
      purification process; in addition, a UV absorbance at wavelength 254 nm and total
      organic carbon amount were measured. A special aim was to study the performance
      and the capacity of the activated carbon filtration in the natural organic matter
      removal. Four of the activated carbon filters were monitored over the period of 1
      year. Depending on the regeneration of the activated carbon filters, filtration
      was effective to a degree but did not significantly remove the smallest molar
      mass organic matter fraction. Activated carbon filtration was most effective in
      the removal of intermediate molar mass compounds (range 1,000-4,000 g/mol).
      Regeneration of the carbon improved the removal capacity considerably, but
      efficiency was returned to a normal level after few months.

PMID- 16091291
TI  - Personality disorder traits associated with risk for unipolar depression during
      middle adulthood.
AB  - Data from the Children in the Community Study, a prospective longitudinal
      investigation, were used to investigate the association of personality disorder
      (PD) traits, evident by early adulthood, with risk for the development of
      unipolar depressive disorders by middle adulthood. Antisocial, borderline,
      dependent, depressive, histrionic, and schizotypal PD traits, identified between
      ages 14 and 22, were significantly associated with risk for dysthymic disorder
      (DD) or major depressive disorder (MDD) by a mean age of 33 after a history of
      unipolar depression and other psychiatric disorder was controlled statistically.
      Individuals without a history of unipolar depression who met diagnostic criteria
      for > or =1 PD by a mean age of 22 were at elevated risk for DD or MDD by a mean
      age of 33 years. Individuals identified as having a DSM-IV Cluster A (paranoid,
      schizoid, or schizotypal) or Cluster C (avoidant, dependent, obsessive
      compulsive) PD by a mean age of 22 years were at elevated risk for recurrent or
      chronic unipolar depression. The findings of this study suggest that some types
      of PD traits that become evident by early adulthood may contribute to an
      increased risk for the development or recurrence of unipolar depressive disorders
      by middle adulthood.

PMID- 16091292
TI  - Cerebrospinal fluid interferon-gamma-inducible protein 10 (IP-10, CXCL10) in HIV
      1 infection.
AB  - Interferon-gamma-inducible protein (IP-10 or CXCL10) is a potent chemoattractant
      and has been suggested to enhance retrovirus infection and mediate neuronal
      injury. In order to assess this chemokine in central nervous system (CNS) HIV
      infection, we measured the cerebrospinal fluid (CSF) and plasma concentrations of
      CXCL10 by immunoassay in samples derived from 97 HIV-infected subjects across a
      spectrum of immunological progression and CNS complications and from 16 HIV
      seronegative control subjects studied at three clinical centers between 1994 and
      2001. We also examined changes in the CSF and plasma CXCL10 concentrations in 30
      subjects starting and three stopping antiretroviral therapy. CSF CXCL10
      concentrations: (1) correlated with CSF HIV RNA and white blood cell (WBC)
      counts, but not with blood CXCL10, HIV RNA, or CD4 counts; (2) were increased in
      subjects with primary and asymptomatic HIV infections and AIDS dementia complex,
      but less frequently in those with more advanced infection, with or without CNS
      opportunistic diseases except cytomegalovirus encephalitis; (3) decreased in
      subjects starting antiretroviral in association with decreases in CSF and plasma
      HIV RNA and CSF WBCs; and (4) conversely, increased in subjects stopping
      treatment in parallel with CSF HIV RNA and WBCs. These results confirm that CSF
      CXCL10 associates closely with both CSF HIV and WBCs and suggest that this
      chemokine may be both a response to and contributing determinant of local
      infection. High CSF levels may be useful in the diagnosis of ADC in subjects with
      advanced immunosuppression in whom CMV encephalitis has been ruled out, though
      this issue requires further study.

PMID- 16091293
TI  - PPARgamma antagonists exacerbate neural antigen-specific Th1 response and
      experimental allergic encephalomyelitis.
AB  - Peroxisome proliferator-activated receptor-gamma is a nuclear receptor
      transcription factor that regulates cell growth, differentiation and homeostasis.
      PPARgamma agonists have been used in the treatment of obesity, diabetes, cancer
      and inflammation. We and others have shown recently that PPARgamma agonists
      ameliorate experimental allergic encephalomyelitis (EAE), a Th1 cell-mediated
      autoimmune disease model of multiple sclerosis (MS). We have further shown that
      PPARgamma agonists inhibit EAE through blocking IL-12 signaling leading to Th1
      differentiation and the PPARgamma-deficient heterozygous mice (PPARgamma(+/-))
      develop an exacerbated EAE. In this study, we show that in vivo treatment (i.p.)
      with 100 mug PPARgamma antagonists, Bisphenol A diglycidyl ether (BADGE) or 2
      Chloro-5-nitro-N-(4-pyridyl)benzamide (T0070907), on every other day from day 0
      to 30, increased the severity and duration of EAE in C57BL/6 wild-type and
      PPARgamma(+/-) mice. The exacerbation of EAE by PPARgamma antagonists associates
      with an augmented neural antigen-induced T cell proliferation, IFNgamma
      production or Th1 differentiation. These results further suggest that PPARgamma
      is a critical physiological regulator of CNS inflammation and demyelination in
      EAE.

PMID- 16091294
TI  - Repression of interferon-gamma-induced inducible nitric oxide synthase (iNOS)
      gene expression in microglia by sodium butyrate is mediated through specific
      inhibition of ERK signaling pathways.
AB  - We have reported recently that sodium butyrate suppressed IFN-gamma, but not the
      LPS-mediated induction of nitric oxide and TNF-alpha in microglia via the
      specific inhibition of NF-kappaB. In order to further determine the upstream
      signaling mechanism involved in the IFN-gamma-specific down-regulation of iNOS by
      sodium butyrate in microglia, this study investigated the effect of sodium
      butyrate on the MAP kinase activities. Sodium butyrate significantly repressed
      the phosphorylation of ERK induced by IFN-gamma, but had little effect on that
      induced by LPS. This suggests that sodium butyrate suppresses the IFN-gamma
      induced iNOS expression by inhibiting the ERK to NF-kappaB pathway. In addition,
      it was found that sodium butyrate suppressed the IFN-gamma-induced interferon
      regulatory factor 1 (IRF-1) expression via the inhibition of ERK. Therefore, the
      ERK signaling pathway appears to play a key role in the sodium butyrate-mediated
      down-regulation of iNOS in the IFN-gamma-stimulated microglia.

PMID- 16091295
TI  - Detection of Aspergillus fumigatus hyphae in respiratory secretions by membrane
      filtration, fluorescent labelling and laser scanning.
AB  - The detection of Aspergillus fumigatus hyphae in bronchoalveolar lavage fluid
      (BAL) and sputum is diagnostically useful in patients at risk of invasive
      aspergillosis. We report a dedicated enzymatic-chemical sample pretreatment that
      allows the application of a previously described solid phase cytometry (SPC)
      method for detection of A. fumigatus hyphae in sputum and BAL samples. Non
      specific detection of fungal hyphae by SPC is based on a 'viability' staining
      using carboxyfluorescein diacetate. For a specific detection of A. fumigatus
      hyphae by SPC, viability staining is combined with a pre-incubation at 45 degrees
      C, immunofluorescent labelling and microscopic recognition of the characteristic
      hyphal morphology. Low numbers of A. fumigatus hyphae (2-10 hyphae/sample) have
      now been demonstrated in spiked sputum using the non-specific and specific
      staining in 2.5 and 8.5 h, respectively.

PMID- 16091296
TI  - Stochastic modelling of individual cell growth using flow chamber microscopy
      images.
AB  - In this paper, we analysed individual cell growth images obtained by flow chamber
      microscopy system. We used replicate flow chamber experiment data as reported by
      [Elfwing, A., Le Marc, Y., Baranyi, J., Ballagi, A., 2004. Observing the growth
      and division of large number of individual bacteria using image analysis. Applied
      and Environmental Microbiology 70, 675-678] involving both unstressed and heat
      shocked Listeria innocua cells. After observing the kinetics of a large number of
      cells, we propose a new stochastic model for their individual growth. By
      comparing our model with other existing models in the literature, we demonstrate
      that ours can accurately describe the growth of both stressed and unstressed
      cells. Our results indicate that the lag period, in terms of cell division,
      coincides dominantly with a lag period in terms of cell size. We also reveal
      various connections between cell length, lag time and cell division models.
      Finally, we present the results of our investigation on the effect of the
      duration of sublethal heat shock on the found growth properties.

PMID- 16091297
TI  - Discrimination of Listeria monocytogenes contaminated commercial Japanese meats.
AB  - Discrimination was attempted on 14 Listeria monocytogenes strains isolated from
      commercially available Japanese pork and chicken. Examination of the isolates was
      performed by restriction fragment length polymorphism (RFLP) analysis of the
      chromosomal DNA and amplified products and comparison of the nucleotide sequences
      of the amplified products. A polymorphism region containing the repeated
      sequences in the iap gene was amplified by the polymerase chain reaction (PCR).
      The genetic analyses could discriminate the 14 isolates in combination with
      traditional serotyping, and some strains isolated from different meats were
      confirmed to have a genetically close relationship. Genetic analyses used in the
      present study would be useful for the elucidation of the pathogen tracks from
      contaminated sources to humans and of the ecological niche in the food
      environment.

PMID- 16091298
TI  - Role of C-terminal regions of the C-terminal fragment of Clostridium perfringens
      enterotoxin in its interaction with claudin-4.
AB  - Claudin family proteins, which contain 4 transmembrane domains, play a pivotal
      role in the barrier function of tight junctions (TJs) in epithelial sheets. We
      previously found that a modulator of claudin-4, the C-terminal fragment of
      Clostridium perfringens enterotoxin (C-CPE), is a potent enhancer of jejunal drug
      absorption in rats. But the effects of C-CPE on the barrier function of TJs have
      never been fully understood. In the present study, we investigated the effects of
      C-CPE on the barrier function of TJs in Caco-2 monolayer and characterized the
      functional domain of C-CPE that is responsible for interaction with claudin-4. To
      evaluate the effects of C-CPE on the barrier function of TJs, we measured
      transepithelial electric resistance (TER) in Caco-2 monolayer cells seeded onto
      polycarbonate filters. Treatment of Caco-2 cells with C-CPE resulted in a
      decrease in TER. But, deletion of the 30 C-terminal amino acids of C-CPE, which
      is the putative binding domain for claudin, attenuated the decrease in TER
      values. Moreover, ablation of the 16 C-terminal amino acids of C-CPE also
      resulted in attenuation of the decrease in TER values. The C-terminal-deleted C
      CPEs did not interact with claudin-4 or the extracellular domain 2 of claudin-4,
      which is the C-CPE binding site. These results suggest that the 16 C-terminal
      amino acids of C-CPE are responsible for the interaction of C-CPE and claudin-4
      following the disruption of TJ barrier function.

PMID- 16091299
TI  - Subsurface sediment contamination during borehole drilling with an air-actuated
      down-hole hammer.
AB  - Drilling methods can severely alter physical, chemical, and biological properties
      of aquifers, thereby influencing the reliability of water samples collected from
      groundwater monitoring wells. Because of their fast drilling rate, air-actuated
      hammers are increasingly used for the installation of groundwater monitoring
      wells in unconsolidated sediments. However, oil entrained in the air stream to
      lubricate the hammer-actuating device can contaminate subsurface sediments.
      Concentrations of total hydrocarbons, heavy metals (Cu, Ni, Cr, Zn, Pb, and Cd),
      and nutrients (particulate organic carbon, nitrogen, and phosphorus) were
      measured in continuous sediment cores recovered during the completion of a 26-m
      deep borehole drilled with a down-hole hammer in glaciofluvial deposits. Total
      hydrocarbons, Cu, Ni, Cr and particulate organic carbon (POC) were all measured
      at concentrations far exceeding background levels in most sediment cores.
      Hydrocarbon concentration averaged 124 +/- 118 mg kg(-1) dry sediment (n = 78
      samples) with peaks at depths of 8, 14, and 20 m below the soil surface (maximum
      concentration: 606 mg kg(-1)). The concentrations of hydrocarbons, Cu, Ni, Cr,
      and POC were positively correlated and exhibited a highly irregular vertical
      pattern, that probably reflected variations in air loss within glaciofluvial
      deposits during drilling. Because the penetration of contaminated air into the
      formation is unpreventable, the representativeness of groundwater samples
      collected may be questioned. It is concluded that air percussion drilling has
      strong limitations for well installation in groundwater quality monitoring
      surveys.

PMID- 16091300
TI  - Antidepressant drug induced alterations in binding to central dopamine
      transporter sites in the Wistar Kyoto rat strain.
AB  - The Wistar Kyoto (WKY) rat has been proposed as an animal model of depressive
      behavior. Exposing WKY rats to stress stimulation produces symptoms such as
      anhedonia, psychomotor retardation, ambivalence and negative memory bias. Given
      the role of the mesolimbic dopamine (DA) system in cognitive, emotional and
      motivational behaviors, we previously examined the distribution of DA transporter
      (DAT) sites in the brains of WKY compared to Wistar (WIS) and Sprague-Dawley (S
      D) rats. WKY rats exhibited significant differences in DAT binding sites in the
      cell body as well as mesolimbic areas compared to the other strains. It was
      reasoned that these differences may lead to altered synaptic levels of DA in
      specific brain regions thus contributing to the behavioral differences observed
      in this rat strain. Thus, the present study examined whether repeated treatment
      with antidepressant drugs that block the uptake of DA (nomifensine and bupropion)
      would modify [3H]-GBR12935 binding to DAT sites in WKY rats compared to WIS and S
      D rats. The results indicate that while nomifensine and bupropion increased the
      binding of [3H]-GBR12935 to DAT sites in the mesocorticolimbic regions in WKY
      rats, these drugs increased the binding of [3H]-GBR12935 to DAT sites in the cell
      body areas in WIS rats but not in S-D and WKY rats. The data from this study
      suggest that antidepressant induced alterations in DAT sites in the
      mesocorticolimbic brain regions may play a role in the behavioral improvement
      seen in WKY rats, as measured by the Open Field Test (OFT) and the Porsolt Forced
      Swim Test (FST).

PMID- 16091301
TI  - Decoding the auditory corticofugal systems.
AB  - The status of the organization of the auditory corticofugal systems is
      summarized. These are among the largest pathways in the brain, with descending
      connections to auditory and non-auditory thalamic, midbrain, and medullary
      regions. Auditory corticofugal influence thus reaches sites immediately
      presynaptic to the cortex, sites remote from the cortex, as in perolivary regions
      that may have a centrifugal role, and to the cochlear nucleus, which could
      influence early central events in hearing. Other targets include the striatum
      (possible premotor functions), the amygdala and central gray (prospective limbic
      and motivational roles), and the pontine nuclei (for precerebellar control). The
      size, specificity, laminar origins, and morphologic diversity of auditory
      corticofugal axons is consonant with an interpretation of multiple roles in
      parallel descending systems.

PMID- 16091302
TI  - Fungal glucoamylases.
AB  - Fungi are employed to produce industrially important glucoamylases. Most
      glucoamylases are glycosylated. Glycosylation enhances the enzyme stability.
      Glucoamylases contain both starch binding and catalytic binding domains, the
      former being responsible for activity on raw (insoluble) starch. Proteases may
      act on this domain causing the enzyme to lose its activity on insoluble starch.
      Optimal activity is observed at pH 4.5 to 6.5 and 50 to 70 degrees C.
      Glucoamylases contain up to 7 sub-sites with highly varying affinity. They can be
      produced by different methods including submerged, solid state and semi-solid
      state fermentation processes.

PMID- 16091303
TI  - TrkA signalling pathways in human airway smooth muscle cell proliferation.
AB  - NGF may play a role in airway inflammation and hyperresponsiveness. We studied
      its possible involvement in airway remodelling and report here its proliferative
      effect and its receptor and signalling pathways in human airway smooth muscle
      cells in culture (HASMC). Proliferation of HASMC induced by NGF (0.1-10 pM) was
      assessed by the XTT and BrdU techniques with and without kinase inhibitors.
      Immunoprecipitation and Western blotting were used to study phosphorylation of
      TrkA and MAPK. NGF caused dose-dependent proliferation of HASMC and induced TrkA
      phosphorylation, both abolished by the tyrosine-kinase inhibitor K252a. PI3K and
      JNK inhibitors had no effect. PKC inhibitors partially inhibited NGF-induced
      proliferation and totally abolished p38 phosphorylation but did not affect ERK1/2
      phosphorylation. The rafK inhibitor decreased NGF-induced proliferation, and
      totally abolished ERK1/2 phosphorylation, but did not affect p38 phosphorylation.
      This finding was confirmed by the decrease of NGF-induced proliferation after
      treatment with inhibitors of the p38 or of ERK1/2 pathways. In conclusion, NGF
      activation of the TrkA receptor involves two distinct signalling pathways: PKC
      selectively activates p38, and the ras/raf pathway selectively activates ERK1/2.
      Both are necessary to induce HASMC proliferation.

PMID- 16091304
TI  - Preparation of enzymatically active recombinant class III protein deacetylases.
AB  - Class III histone deacetylases, or sirtuins, are homologous to the Saccharomyces
      cerevisiae transcriptional regulator SIR2. The class III enzymes are
      characterized by their dependence on nicotinamide adenine dinucleotide (NAD+).
      This cofactor serves as an acetyl-group acceptor in the deacetylation reaction
      generating O-acetyl-ADP-ribose. Enzymatic activity of sirtuin can be measured in
      vitro using recombinant proteins purified from mammalian cells after
      overexpression or after purification from Escherichia coli. This review discusses
      protocols for the purification of enzymatically active human sirtuin 1, 2, and 3
      and their activities on histone and nonhistone substrates.

PMID- 16091305
TI  - Nitric oxide and mitochondrial biogenesis: a key to long-term regulation of
      cellular metabolism.
AB  - Mitochondria, the site of oxidative energy metabolism in eukariotic cells, are a
      highly organised structure endowed with different enzymes and reactions localized
      in discrete membranes and aqueous compartments. Mitochondrial function is
      regulated in complex ways by several agonists and environmental conditions,
      through activation of specific transcription factors and signalling pathways. A
      key player in this scenario is nitric oxide (NO). Its binding to cytochrome c
      oxidase in the mitochondrial respiratory chain, which is reversible and in
      competition with oxygen, plays a role in acute oxygen sensing and in the cell
      response to hypoxia. Evidence of the last two years showed that NO has also long
      term effects, leading to biogenesis of functionally active mitochondria, that
      complement its oxygen sensing function. Mitochondrial biogenesis is triggered by
      NO through activation of guanylate cyclase and generation of cyclic GMP, and
      yields formation of functionally active mitochondria. Thus, the combined action
      of NO at its two known intracellular receptors, cytochrome c oxidase and
      guanylate cyclase, appears to play a role in coupling energy generation with
      energy demand. This may explain why dysregulation of the NO signalling pathway is
      often associated with the pathogenesis of metabolic disorders.

PMID- 16091306
TI  - Kinetic and stability analysis of PKU mutations identified in BH4-responsive
      patients.
AB  - From all the different molecular mechanisms put forward to explain the basis of
      BH4 responsiveness in PKU patients, a clear picture is now emerging based on the
      results from expression studies performed with a number of missense mutations
      identified in patients with a positive response in BH4 loading tests. Two of the
      proposed mechanisms, namely decreased binding affinity of the mutant proteins for
      the natural cofactor and stabilization effect of BH4, have been confirmed for
      several PKU mutations and the results are reviewed here. The actual view supports
      a multifactorial basis of the response, highlighting the necessity of detailed in
      vitro characterization of each mutant PAH protein. Several of the confirmed
      molecular mechanisms may be operating simultaneously, as exemplified in the data
      presented, and this may result in different degrees of BH4 responsiveness.

PMID- 16091307
TI  - Tetrahydrobiopterin-responsive phenylketonuria: the New South Wales experience.
AB  - Recent studies have shown that a subgroup of phenylketonuric patients respond to
      high doses of BH4 (20 mg/kg) by a decrease of plasma phenylalanine. A clinically
      significant response has been defined as a decrease in phenylalanine by more than
      30% within 24 h, after a BH4 challenge. We report our experience with 37 patients
      diagnosed with hyperphenylalaninemia, mild, moderate, or classical
      Phenylketonuria (PKU) using a seven day combined BH4 and phenylalanine load. Nine
      of the 37 patients responded with a 30% decrease in their phenylalanine levels in
      the first 8 h of treatment. A total of 17 patients (46%) had a decrease of at
      least 30% during the study period. This study confirms that a significant number
      of patients with mild to moderate PKU will respond to a BH4 load. Furthermore, it
      confirms that the seven-day phenylalanine test is more sensitive in detecting BH4
      responsive patients.

PMID- 16091308
TI  - Response inhibition and set shifting in patients with frontal lobe epilepsy or
      temporal lobe epilepsy.
AB  - Patients with frontal lobe epilepsy (FLE), patients with temporal lobe epilepsy
      (TLE), and matched controls were administered a test of response inhibition and
      set shifting (switching) (Color Word Interference Test, CWIT). Patients with FLE
      were impaired relative to the controls across all conditions of the CWIT, with
      the FLE patients showing disproportionate impairment in the Inhibition and
      Inhibition/Switching conditions. In contrast, the TLE patients did not differ
      from controls. Further analysis of the patient groups revealed that patients with
      left FLE were impaired relative to those with right FLE, left TLE, and right TLE
      in the Inhibition condition. In the Inhibition/Switching condition, patients with
      left FLE and left TLE were impaired relative to their right-sided counterparts.
      Finally, performance by the TLE group in the Inhibition/Switching condition was
      correlated with seizure frequency. These data suggest that patients with FLE, but
      not TLE, show impaired inhibition and set shifting relative to controls. In
      addition, side of the seizure focus and seizure frequency may contribute to
      executive dysfunction in patients with epilepsy.

PMID- 16091309
TI  - Gynaecological malignancy in pregnancy.

PMID- 16091310
TI  - A study of maternal plasma beta-endorphin in pre-eclamptic women during labour.
AB  - This prospective study was undertaken to determine the maternal plasma beta
      endorphin levels in pre-eclamptic women during labour and to explore any
      correlation between the levels and the severity of pre-eclampsia. A total of 50
      primiparous women at term were recruited over a period of 5 years. Twenty-five
      with pre-eclampsia and 25 healthy women considered as a control group. The mean
      concentration of maternal plasma beta-endorphin in pre-eclamptic group (22.73+/
      8.02 pmol/l) was significantly lower (p<0.001) than that of the control group
      (48.38+/-5.94 pmol/l). A highly significant (p<0.001) negative correlation was
      found between maternal plasma beta-endorphin levels and both systolic and
      diastolic blood pressures in pre-eclamptic group.

PMID- 16091311
TI  - Coping with placenta praevia and accreta in a DGH setting and words of caution.
AB  - The incidence of placenta praevia and accreta has been increasing with rising
      caesarean section rates. We highlight the increasing incidence of severe post
      partum haemorrhage due to placenta accreta. Four cases occurred within 3 years
      (2002--2004) in a small District General Hospital (DGH) with a delivery rate of
      1,800 per year. All of the cases had previous caesarean sections and three had an
      associated anterior low-lying placenta. These patients were diagnosed to have
      placenta accreta in the third stage of labour, as the placenta was completely
      adherent and was difficult to remove. However, two of them had a provisional
      diagnosis made of placenta accreta and prophylactic measures had been taken in
      the form of counselling and consent for possible hysterectomy. Patients were
      counselled regarding this condition, and the possible need for hysterectomy was
      discussed. Two of them had to be managed by post-partum hysterectomy and the
      other two were treated conservatively. The purpose of writing these case reports
      is to warn others of the need for vigilance, particularly in keeping their
      primary caesarean section rates down and being prepared for long-term
      complications.

PMID- 16091312
TI  - Does discussion of possible scar rupture influence preferred mode of delivery
      after a caesarean section?
AB  - Using retrospective and prospective analyses of antenatal records, it was found
      that by 2003, discussions about the options for delivery after one lower segment
      caesarean section (LSCS) were almost always documented in antenatal notes,
      compared with only rare entries in 1993; specific mention of the risks of scar
      rupture were made in just under 50% in 2003. There was a considerable reduction
      in the proportion of women whose preference was to labour in 2003 compared with
      1993 and also in the number who ultimately delivered vaginally. There was,
      however, no evidence that those women with whom possible scar rupture had been
      discussed were discouraged from attempting vaginal delivery. These data suggest
      that, contrary to expectations, increasing patients' involvement in their
      management in this situation does not result in fewer caesarean sections.

PMID- 16091313
TI  - Decision - delivery interval and perinatal outcome in emergency caesarean
      sections.
AB  - Recent studies have cast doubt on the recommended 30-min decision--delivery
      interval (DDI) in emergency caesarean sections. The practicability,
      justification, anticipated beneficial effect on neonatal outcome and its medico
      legal implications have been questioned. We set out to determine (1) the DDI for
      emergency caesarean sections in two Nigerian tertiary care centres (2) the effect
      of DDI on perinatal outcome (particularly if the DDI is longer than the
      internationally recommended 30 min) and (3) the factors causing delays in
      intervention if any. This was a prospective observational study of consecutive
      cases of emergency caesarean sections performed at the two centres over an 8
      month period. The main outcome measures were: indication for the caesarean, the
      decision-baby delivery interval, 1-min and 5-min Apgar scores, newborn admission
      to special care, perinatal death and reasons for any delay in decision - delivery
      interval beyond 30 min. The data were analysed with descriptive and inferential
      statistics and regression equations at the 95% confidence level. A total of 224
      emergency caesarean sections were performed in the two institutions within the
      period of study. None of the caesarean sections was done within the recommended
      30-min interval. Despite this, there was no significant correlation between the
      DDI and perinatal outcome. The major causes of delays in DDI were anaesthetic
      delays in both centres and difficulty in sourcing essential materials in one of
      the centres. The recommended 30-min DDI in emergency caesarean section is not
      currently feasible in Nigeria. Although the 30-min interval should remain the
      gold standard, DDI up to 3 hours may not be incompatible with good perinatal
      outcome as shown in this study. As in other studies, anaesthetic delay is the
      major cause of delay in carrying out emergency caesarean sections. Finally, since
      prolonged DDI may not be the cause of an adverse perinatal outcome in the
      majority of cases, litigation on these grounds may be unjustified.

PMID- 16091314
TI  - Are we increasing serious maternal morbidity by postponing termination of
      pregnancy in severe pre-eclampsia/eclampsia?
AB  - The objective of this study was to evaluate the impact of admission--delivery
      interval on maternal morbidity in patients with severe pre-eclampsia/eclampsia.
      This was a retrospective study, which involved review of case sheets of 188 women
      (admitted to St John's Medical College Hospital during the year 2000--2001 with
      the above diagnosis). The incidence of severe pre-eclampsia and eclampsia was
      5.18% (188/3,627) with 119 primigravida and 69 multigravida. The incidence of
      serious maternal complications in the post partum period was 17% (11/68) in the
      category of women who delivered within 12 hours of admission compared with 40.6%
      (28/69) in the 12--48-h category and 60.8% (31/51) in the>48-h category. The
      incidence of serious maternal complications in the subset with HELLP (hemolysis,
      elevated liver enzymes, and low platelet count) syndrome was 33.4% (7/21) in
      the<or=12-h category compared with 90.9% (20/22)in the>12-h. We concluded that
      termination of pregnancy within 12 hours of admission in severe pre
      eclampsia/eclampsia especially in patients with HELLP syndrome helps to prevent
      avoidable serious maternal morbidity.

PMID- 16091315
TI  - Atypical eclampsia.

PMID- 16091316
TI  - Maternal end-pregnancy ponderal index and birth weight.

PMID- 16091317
TI  - Should loose fascial sutures be removed in the 1st postoperative week in patients
      with superficial wound dehiscence and intact fascia after caesarean section using
      a Pfannenstiel incision?

PMID- 16091318
TI  - Acid aspiration prophylaxis and caesarean delivery: time for another close look.

PMID- 16091319
TI  - The impact of introduction of selective episiotomy policy on the rate of
      episiotomy and associated perineal trauma.

PMID- 16091320
TI  - Twenty-five sacrospinous ligament fixation procedures in a district general
      hospital: our experience.
AB  - The aim of this study was to assess the safety and medium term efficacy of
      sacrospinous ligament fixation procedure for grade 2 and grade 3-uterovaginal
      prolapse. This retrospective case study was performed between 1 July 2000 - 4
      July 2003 at a District General Hospital in Scotland. For data collection,
      patient files, theatre records and the computer database were reviewed. The
      procedure was performed on 25 women. The subjective cure rate in our department
      was 23/25 (92%) and the recurrence rate was 2/25 (8%). These two patients
      underwent repeat surgery successfully. The mean follow-up time was 2 years (range
      6 months to 3 years). The immediate postoperative complication rate was 2/25
      (8%). The late postoperative complications rate was 7/25(28%). We concluded that
      the sacrospinous ligament fixation is safe and effective with good medium-term
      results and few postoperative complications. It should be regarded as a good
      primary procedure in a District General Hospital.

PMID- 16091321
TI  - Incidence of genital Chlamydia trachomatis infection in the male partners
      attending an infertility clinic.
AB  - Chlamydia trachomatis is an important pathogen in the aetiology of pelvic
      inflammatory disease, resulting in female infertility. If all female infertility
      patients are screened for silent genital chlamydia infection, should the male
      partners of these patients also be screened to decrease the risk of re-infection?
      To determine the incidence of current and present male infection with C.
      trachomatis, we carried out a prospective clinical study. We studied 100
      consecutive new male partners of patients seen in the infertility clinic. The
      infertility was of at least 12 months duration. We used polymerase chain reaction
      detection of C. trachomatis in urine specimens and microimmunofluorescence
      serology was performed to detect both past and current infection. The female
      partners were also screened for chlamydia infection by cervical swabs and
      serology. In five male patients (5%) C. trachomatis DNA was detected in the urine
      specimen by polymerase chain reaction. Microimmunofluorescence serology was
      positive in five patients (5%). One of the subjects had positive serology and
      urine polymerase chain reaction testing. The proportion of male partners with
      current or previous C. trachomatis infection was therefore 9% (95% CI 3.39 -
      14.60). Seven female patients had positive serology results (7%), one of whom
      also had a positive cervical swab result indicating current infection with the
      pathogen. In four cases, both the male and female partner had positive serology
      results. The cost of screening for C. trachomatis is cheaper than treating the
      complications of undiagnosed genital Chlamydia infection, which is implicated in
      tubal disease leading to infertility. The results suggest that routine screening
      of male partners in an infertility setting may be justified.

PMID- 16091322
TI  - Delayed diagnosis of cervical cancer in young women.
AB  - This study aims to determine whether women under 35 years presenting with
      cervical cancer experience delays between presentation and diagnosis. All women
      referred with cervical cancer to the gynaecological cancer centre for the North
      London Cancer Network from January 2002 to December 2004 were identified
      retrospectively. Clinical presentation and time interval from symptoms to
      diagnosis were compared between women under and women over 35 years. A total of
      105 women were included. Median age at diagnosis was 45 years (range 23--88).
      Twenty-two women (19%) were under 35 years at presentation and 17 had persistent
      symptoms prior to diagnosis. Median time from initial presentation to diagnosis
      in this group was 9 months (range 3--24 months); significantly longer than in the
      older group (9 vs 2 months; p=0.0009). Although cervical cancer is relatively
      rare in young women, diagnosis should be considered in symptomatic women as delay
      can limit treatment options.

PMID- 16091323
TI  - Serum calcium and magnesium levels in women with detrusor overactivity.
AB  - The aim of this study was to determine whether abnormal serum levels of magnesium
      and calcium occur in women with detrusor overactivity. These were compared with
      the serum level of magnesium and calcium ions in women with urodynamic stress
      incontinence as controls to see whether alteration of these levels offer a
      further therapeutic option. The study included 20 women with urodynamically
      proven detrusor overactivity compared with 20 women with urodynamic stress
      incontinence as controls. A blood test was taken to determine serum levels of
      total magnesium phosphate together with free and corrected calcium. In addition,
      the calcium and magnesium ratio (Ca:Mg) and calcium corrected and magnesium ratio
      (Ca Corr:Mg) were calculated. Both parametric and non-parametric tests were used
      to compare the two groups with respect to these variables. The mean, median and
      standard deviation of the two groups are very similar for each of the variables.
      There is no evidence to suggest that there is any difference between detrusor
      overactivity and urodynamic stress incontinence with respect to these variables.
      This study has shown that there is no abnormal correlation between serum calcium
      and magnesium ions in women with detrusor overactivity. There appears to be no
      therapeutic benefit in calcium and/or magnesium supplements for detrusor
      overactivity.

PMID- 16091324
TI  - Is there a benefit from routine follicular flushing for oocyte retrieval?
AB  - The object of this study was to determine the optimum number of follicular
      flushing for a maximum number of oocytes to be retrieved. This was a prospective
      study, based at a private in vitro fertilization centre (Brentwood Fertility
      Centre, The Essex Nuffield Hospital, Brentwood, Essex UK). Patients attending the
      IVF centre for assisted reproductive technology were studied. We counted the
      number of oocytes obtained with each flushing after primary aspiration of the
      follicle. Some 40% of the oocytes were retrieved with primary aspiration without
      follicular flushing, while up to 82% of oocytes were retrieved with two flushes
      and 97% of oocytes were retrieved in up to four flushes. Only 3% of the remaining
      oocytes were retrieved with 5th and 6th flush. The optimum number of follicular
      flushing was four times, in order to achieve maximum number of oocytes without
      compromising the duration of retrieval and number of oocytes retrieved.

PMID- 16091325
TI  - Evaluation of haemostatic function in Nigerian Norplant acceptors after 12 months
      of use.
AB  - A total of 55 non-breastfeeding informed volunteers were recruited into a
      prospective longitudinal study from a family planning clinic between September
      and December 2002. Blood samples were collected at pre-treatment and at 3, 6 and
      12 months follow-up, for packed cell volume, platelet count, prothrombin and
      activated partial thromboplastin time. Statistical analysis was with paired t
      tests. The level of significance was set at 5%. Each subject received a menstrual
      calendar to chart all bleeding and spotting events. The mean age and weight of
      acceptors were 32.5 +/- 6.1 years and 63.6 +/- 9.6 kg, respectively. Mean packed
      cell volume (PCV) was 35.2 +/- 2.9% at pre-insertion. This rose to significant
      mean +/- SD values of 36.5 +/- 3.1%; p<0.05, 38.5 +/- 2.8%; p<0.0001 and 38.4 +/-
      3.6%; p<0.0001 at 3, 6 and 12 months, respectively when compared with the pre
      insertion mean value. The mean values of the platelet count showed no significant
      change at 3 months (238,448 +/- 68,618 mm(3); p>0.9), compared with pre-treatment
      value (240,545 +/- 96,769 mm(3)). There was a significant reduction in mean
      concentration at 6 months (p<0.009; 191,364 +/- 55,531 mm(3)) and at 12 months
      (p<0.003; 202,773 +/- 81,544 mm(3)) follow-up. The prothrombin and the partial
      thromboplastin time did not show significant change over their pre-insertion mean
      values of 12.0 +/- 1.1 s and 36.9 +/- 2.9 s, respectively. At 12 months, 79.5%
      (35) of the users reported an abnormal menstrual pattern, which included 54.5%
      (24) reduced bleeding pattern, 20.5% (9) increased bleeding and 4.5% (2) of
      combination of patterns. Only 20.5% (9) had a normal menstrual pattern. The
      continuation rate was 98%, as one user discontinued because of headaches.
      Norplant (the registered trademark of the Population Council for levonorgestrel
      subdermal implants) had an effect on the bleeding pattern - mainly reduced
      bleeding. The increase packed cell volume is beneficial in preventing anaemia.
      There was no detrimental effect as a result of the reduced but normal platelet
      count and users were not predisposed to clotting abnormalities.

PMID- 16091326
TI  - An evaluation of the use of an intra-operative uterine tourniquet during multiple
      myomectomy: does this reduce blood loss and the need for blood transfusion?

PMID- 16091327
TI  - An evaluation of troublesome inter-menstrual bleeding in menorrhagic users of the
      LNG-IUS.

PMID- 16091328
TI  - Presumed lupus nephritis with autoimmune haemolysis and thrombocytopenia
      mimicking severe early onset pre-eclampsia and HELLP syndrome.

PMID- 16091329
TI  - Transient blindness complicating primary post-partum haemorrhage: a case report.

PMID- 16091330
TI  - Post-partum aortic dissection.

PMID- 16091331
TI  - Massive inferior vena caval thrombosis: an unusual puerperal case.

PMID- 16091332
TI  - Spontaneous uterine rupture following intercourse in a scarred uterus.

PMID- 16091333
TI  - An ovarian torsion in severe spontaneous ovarian hyperstimulation syndrome
      associated with a singleton pregnancy.

PMID- 16091334
TI  - Ovarian hyperstimulation associated with a spontaneous pregnancy.

PMID- 16091335
TI  - Pregnancy complicated by a fetus with aneurysm of the vein of Galen and
      microcephaly.

PMID- 16091336
TI  - A case of placenta percreta with bladder involvement managed conservatively.

PMID- 16091337
TI  - Bombay blood group and pregnancy: a rare clinical scenario.

PMID- 16091338
TI  - Severe, acute pain following application of Filshie clips: a case of possible
      viscero-visceral sensitization.

PMID- 16091339
TI  - Leiomyomata of the uterus presenting as an abdominal mass in a true
      hermaphrodite.

PMID- 16091340
TI  - Complete androgen insensitivity syndrome with persistent Mullerian derivatives: a
      case report.

PMID- 16091341
TI  - Subphrenic abscess: an unusual complication of vaginal hysterectomy.

PMID- 16091342
TI  - Surgical management of chronic tubo-ovarian actinomycosis simulating malignancy:
      a case report.

PMID- 16091343
TI  - Not all disseminated intra-abdominal lesions are malignant: a case of
      leiomyomatosis peritonealis disseminata.

PMID- 16091344
TI  - Benign cystic teratoma in a pre-pubertal girl.

PMID- 16091345
TI  - Cervical ectopic pregnancy with successful conservative treatment.

PMID- 16091346
TI  - Tape erosion into the vagina.

PMID- 16091347
TI  - Maulik's manoeuvre: a simple and reversible technique for controlling uterine
      haemorrhage.

PMID- 16091349
TI  - Validation of a solvent-free sampler for the determination of low molecular
      weight aliphatic isocyanates under thermal degradation conditions.
AB  - During the thermal degradation of 1,6-hexamethylenediiso- cyanate-based (HDI) car
      paint, the eight most abundant isocyanates generated are isocyanic acid, methyl
      isocyanate, ethyl isocyanate, propyl isocyanate, butyl isocyanate, pentyl
      isocyanate, hexyl isocyanate, and 1,6-hexamethylenediisocyanate. For the first
      time, a method using solvent-free samplers is proposed and validated for the
      simultaneous sampling of all these isocyanates. The sampling efficiency during
      thermal degradation of car paint can be affected by the formation of dust and
      aerosols and by the emission of many chemicals, such as isocyanic acid,
      anhydrides, amines, and alcohols that consume the reagent or interfere in the
      derivatization procedure. Sampling was performed using cassettes containing two 1
      (2-methoxyphenyl)piperazine (MOPIP)-coated glass fiber filters (MFs)
      (approximately 4.9 mg per filter) and compared with bubblers containing 15 mL of
      MOPIP solution in toluene (1.0 mg/mL(-1)) and with bubblers backed with MFs. A
      DIN 53436 laboratory scale furnace was used to generate the isocyanates under
      thermal degradation conditions. For an aliphatic isocyanate concentration of
      approximately 42 microg(NCO) m(-3), no significant difference in sampling
      efficiency was observed between the three techniques studied, thus confirming the
      sampling efficiency of the MFs. The samples were analyzed using high-performance
      liquid chromatography coupled with electrospray/tandem mass spectrometry.
      Quantification was performed in daughter mode monitoring (MOPIP+H)(+) fragments.
      For concentrations between 0.013 microg(NCO) mL(-1) and 0.52 microg(NCO) mL(-1)
      for the monoisocyanates, and between 0.026 microg(NCO) mL(-1) and 1.04
      microg(NCO) mL(-1) for the HDI, the correlation coefficients were in the 0.9974
      0.9996 range (n = 18). Analytical reproducibility and precision were better than
      95.4% and 94.9%, respectively, for all the isocyanates. The instrumental
      detection limits, defined as three times the standard deviation measured at the
      lowest point on the calibration curve were in the 1.8-3.0 ng(NCO) mL(-1) range (n
      = 8), which corresponds to about 0.37-0.60 microg(NCO) m(-3) for a 15-L air
      sample when the filters are desorbed in 3 mL.

PMID- 16091350
TI  - Exposures to refractory ceramic fibers in manufacturing and related operations: a
      10-year update.
AB  - Refractory ceramic fiber (RCF) is a man-made vitreous fiber used for its
      insulating properties. Since 1987, the work environment of approximately 800
      persons employed in fiber manufacture or production operations directly related
      to manufacturing has been monitored to evaluate exposure levels. Samples were
      collected quarterly from the breathing zones of randomly selected workers. The
      measurements from those working in areas of similar activities and exposure
      controls (dust zones or homogeneous exposure groups) were used to calculate a
      mean exposure during identified time periods. Persons who spent all of their work
      time in one zone/group were assigned this mean exposure; those with
      responsibilities in more than one area were assigned an exposure based on a time
      weighted formula. A total of 3213 measurements were used to estimate exposure for
      130 job titles; because of the mobile jobs, many samples contribute to the
      estimates of exposure for multiple job titles. The majority of exposure estimates
      (53%) have remained stable over the operational history of the plant reported
      here. For 32 job titles (25%) exposures have decreased, and for 28 job titles
      (22%) exposures have increased. Of the 122 job titles active in 2001, 97 (79%)
      exposures were estimated to be at 0.25 f/cc or lower; 8 (7%) had an exposure
      exceeding 0.5 f/cc (range 0.51-0.80) and 17 (14%) of these exposure estimates
      were in the range of > 0.25 f/cc to 0.5 f/cc. The continuing program to measure
      exposure supports a respiratory health surveillance program in these facilities.

PMID- 16091351
TI  - Treating cancer by blocking cell signals.

PMID- 16091352
TI  - Extended lymph node dissection for gastric cancer: who may benefit? Final results
      of the randomized Dutch gastric cancer group trial.

PMID- 16091355
TI  - Mechanisms underlying energy-independent transfer of lipoproteins from LolA to
      LolB, which have similar unclosed {beta}-barrel structures.
AB  - The Lol system, comprising five Lol proteins, transfers lipoproteins from the
      inner to the outer membrane of Escherichia coli. Periplasmic LolA accepts
      lipoproteins from LolCDE in the inner membrane and immediately transfers them to
      LolB, a receptor anchored to the outer membrane. The unclosed beta-barrel
      structures of LolA and LolB are very similar to each other and form hydrophobic
      cavities for lipoproteins. The lipoprotein transfer between these similar
      structures is unidirectional and very efficient, but requires no energy input. To
      reveal the mechanisms underlying this lipoprotein transfer, Arg and Phe at
      positions 43 and 47, respectively, of LolA were systematically mutagenized. The
      two residues were previously found to affect abilities to accept and transfer
      lipoproteins. Substitution of Phe-47 with polar residues inhibited the ability to
      accept lipoproteins from the inner membrane. No derivatives caused periplasmic
      accumulation of lipoproteins. In contrast, many Arg-43 derivatives caused unusual
      periplasmic accumulation of lipoproteins to various extents. However, all
      derivatives, except one having Leu instead of Arg, supported the growth of cells.
      All Arg-43 derivatives retained the ability to accept lipoproteins from the inner
      membrane, whereas their abilities to transfer associated lipoproteins to LolB
      were variously reduced. Assessment of the intensity of the hydrophobic
      interaction between lipoproteins and Arg-43 derivatives revealed that the LolA
      lipoprotein interaction should be weak, otherwise lipoprotein transfer to LolB is
      inhibited, causing accumulation of lipoproteins in the periplasm.

PMID- 16091356
TI  - Human Sco1 and Sco2 function as copper-binding proteins.
AB  - The function of human Sco1 and Sco2 is shown to be dependent on copper ion
      binding. Expression of soluble domains of human Sco1 and Sco2 either in bacteria
      or the yeast cytoplasm resulted in the recovery of copper-containing proteins.
      The metallation of human Sco1, but not Sco2, when expressed in the yeast
      cytoplasm is dependent on the co-expression of human Cox17. Two conserved
      cysteines and a histidyl residue, known to be important for both copper binding
      and in vivo function in yeast Sco1, are also critical for in vivo function of
      human Sco1 and Sco2. Human and yeast Sco proteins can bind either a single Cu(I)
      or Cu(II) ion. The Cu(II) site yields S-Cu(II) charge transfer transitions that
      are not bleached by weak reductants or chelators. The Cu(I) site exhibits
      trigonal geometry, whereas the Cu(II) site resembles a type II Cu(II) site with a
      higher coordination number. To identify additional potential ligands for the
      Cu(II) site, a series of mutant proteins with substitutions in conserved residues
      in the vicinity of the Cu(I) site were examined. Mutation of several conserved
      carboxylates did not alter either in vivo function or the presence of the Cu(II)
      chromophore. In contrast, replacement of Asp238 in human or yeast Sco1 abrogated
      the Cu(II) visible transitions and in yeast Sco1 attenuated Cu(II), but not
      Cu(I), binding. Both the mutant yeast and human proteins were nonfunctional,
      suggesting the importance of this aspartate for normal function. Taken together,
      these data suggest that both Cu(I) and Cu(II) binding are critical for normal Sco
      function.

PMID- 16091357
TI  - Ubiquilin-1 regulates nicotine-induced up-regulation of neuronal nicotinic
      acetylcholine receptors.
AB  - Chronic exposure to nicotine, as in tobacco smoking, up-regulates nicotinic
      acetylcholine receptor surface expression in neurons. This up-regulation has been
      proposed to play a role in nicotine addiction and withdrawal. The regulatory
      mechanisms behind nicotine-induced up-regulation of surface nicotinic
      acetylcholine receptors remain to be determined. It has recently been suggested
      that nicotine stimulation acts through increased assembly and maturation of
      receptor subunits into functional pentameric receptors. Studies of muscle
      nicotinic acetylcholine receptors suggest that the availability of unassembled
      subunits in the endoplasmic reticulum can be regulated by the ubiquitin
      proteosome pathway, resulting in altered surface expression. Here, we describe a
      role for ubiquilin-1, a ubiquitin-like protein with the capacity to interact with
      both the proteosome and ubiquitin ligases, in regulating nicotine-induced up
      regulation of neuronal nicotinic acetylcholine receptors. Ubiquilin-1 interacts
      with unassembled alpha3 and alpha4 subunits when coexpressed in heterologous
      cells and interacts with endogenous nicotinic acetylcholine receptors in neurons.
      Coexpression of ubiquilin-1 and neuronal nicotinic acetylcholine receptors in
      heterologous cells dramatically reduces the expression of the receptors on the
      cell surface. In cultured superior cervical ganglion neurons, expression of
      ubiquilin-1 abolishes nicotine-induced up-regulation of nicotinic acetylcholine
      receptors but has no effect on the basal level of surface receptors.
      Coimmunostaining shows that the interaction of ubiquilin-1 with the alpha3
      subunit draws the receptor subunit and proteosome into a complex. These data
      suggest that ubiquilin-1 limits the availability of unassembled nicotinic
      acetylcholine receptor subunits in neurons by drawing them to the proteosome,
      thus regulating nicotine-induced up-regulation.

PMID- 16091358
TI  - Crystal structures representing the Michaelis complex and the thiouronium
      reaction intermediate of Pseudomonas aeruginosa arginine deiminase.
AB  - L-arginine deiminase (ADI) catalyzes the irreversible hydrolysis of L-arginine to
      citrulline and ammonia. In a previous report of the structure of apoADI from
      Pseudomonas aeruginosa, the four residues that form the catalytic motif were
      identified as Cys406, His278, Asp280, and Asp166. The function of Cys406 in
      nucleophilic catalysis has been demonstrated by transient kinetic studies. In
      this study, the structure of the C406A mutant in complex with L-arginine is
      reported to provide a snapshot of the enzyme.substrate complex. Through the
      comparison of the structures of apoenzyme and substrate-bound enzyme, a substrate
      induced conformational transition, which might play an important role in activity
      regulation, was discovered. Furthermore, the position of the guanidinium group of
      the bound substrate relative to the side chains of His278, Asp280, and Asp166
      indicated that these residues mediate multiple proton transfers. His278 and
      Asp280, which are positioned to activate the water nucleophile in the hydrolysis
      of the S-alkylthiouronium intermediate, were replaced with alanine to stabilize
      the intermediate for structure determination. The structures determined for the
      H278A and D280A mutants co-crystallized with L-arginine provide a snapshot of the
      S-alkylthiouronium adduct formed by attack of Cys406 on the guanidinium carbon of
      L-arginine followed by the elimination of ammonia. Asp280 and Asp166 engage in
      ionic interactions with the guanidinium group in the C406A ADI. L-arginine
      structure and might orient the reaction center and participate in proton
      transfer. Structure determination of D166A revealed the apoD166A ADI. The
      collection of structures is interpreted in the context of recent biochemical data
      to propose a model for ADI substrate recognition and catalysis.

PMID- 16091359
TI  - Phospholipid scramblase 1 binds to the promoter region of the inositol 1,4,5
      triphosphate receptor type 1 gene to enhance its expression.
AB  - Phospholipid scramblase 1 (PLSCR1) is a multiply palmitoylated, endofacial
      membrane protein originally identified based on its capacity to promote
      accelerated transbilayer phospholipid movement in response to Ca(2+). Recent
      evidence suggests that this protein also participates in cell response to various
      growth factors and cytokines, influencing myeloid differentiation, tumor growth,
      and the antiviral activity of interferon. Whereas plasma membrane PLSCR1 was
      shown to be required for normal recruitment and activation of Src kinase by
      stimulated cell surface growth factor receptors, PLSCR1 was also found to traffic
      into the nucleus and to tightly bind to genomic DNA, suggesting a possible
      additional nuclear function. We now report evidence that PLSCR1 directly binds to
      the 5'-promoter region of the inositol 1,4,5-triphosphate receptor type 1 gene
      (IP3R1) to enhance expression of the receptor. Probing a CpG island genomic
      library with PLSCR1 as bait identified four clones with avidity for PLSCR1,
      including a 191-bp fragment of the IP3R1 promoter. Using electrophoretic mobility
      shift and transcription reporter assays, the PLSCR1-binding site in IP3R1 was
      mapped to residues (-101)GTAACCATGTGGA(-89), and the segment spanning Met(86)
      Glu(118) in PLSCR1 was identified to mediate its transcriptional activity. The
      significance of this interaction between PLSCR1 and IP3R1 in situ was confirmed
      by comparing levels of IP3R1 mRNA and protein in matched cells that either
      expressed or were deficient in PLSCR1. These data suggest that in addition to its
      role at the plasma membrane, effects of PLSCR1 on cell proliferative and
      maturational responses may also relate to alterations in expression of cellular
      IP3 receptors.

PMID- 16091360
TI  - Spontaneous thermal motion of the GABA(A) receptor M2 channel-lining segments.
AB  - The gamma-aminobutyric acid type A (GABA(A)) receptor channel opening involves
      translational and rotational motions of the five channel-lining, M2 transmembrane
      segments. The M2 segment's extracellular half is loosely packed and undergoes
      significant thermal motion. To characterize the extent of the M2 segment's
      motion, we used disulfide trapping experiments between pairs of engineered
      cysteines. In alpha1beta1 gamma2S receptors the single gamma subunit is flanked
      by an alpha and beta subunit. The gamma2 M2-14' position is located in the alpha
      gamma subunit interface. Gamma2 13' faces the channel lumen. We expressed either
      the gamma2 14' or the gamma2 13' cysteine substitution mutants with alpha1
      cysteine substitution mutants between 12' and 16' and wild-type beta1. Disulfide
      bonds formed spontaneously between gamma2 14'C and both alpha1 15'C and alpha1
      16'C and also between gamma2 13'C and alpha1 13'C. Oxidation by copper
      phenanthroline induced disulfide bond formation between gamma2 14'C and alpha1
      13'C. Disulfide bond formation rates with gamma2 14'C were similar in the
      presence and absence of GABA, although the rate with alpha1 13'C was slower than
      with the other two positions. In a homology model based on the acetylcholine
      receptor structure, alphaM2 would need to rotate in opposite directions by
      approximately 80 degrees to bring alpha1 13' and alpha1 15' into close proximity
      with gamma2 14'. Alternatively, translational motion of alphaM2 would reduce the
      extent of rotational motion necessary to bring these two alpha subunit residues
      into close proximity with the gamma2 14' position. These experiments demonstrate
      that in the closed state the M2 segments undergo continuous spontaneous motion in
      the region near the extracellular end of the channel gate. Opening the gate may
      involve similar but concerted motions of the M2 segments.

PMID- 16091361
TI  - Inhibition of metabotropic glutamate receptor signaling by the huntingtin-binding
      protein optineurin.
AB  - Huntington disease is caused by a polyglutamine expansion in the huntingtin
      protein (Htt) and is associated with excitotoxic death of striatal neurons. Group
      I metabotropic glutamate receptors (mGluRs) that are coupled to inositol 1,4,5
      triphosphate formation and the release of intracellular Ca(2+) stores play an
      important role in regulating neuronal function. We show here that mGluRs interact
      with the Htt-binding protein optineurin that is also linked to normal pressure
      open angled glaucoma and, when expressed in HEK 293 cells, optineurin functions
      to antagonize agonist-stimulated mGluR1a signaling. We find that Htt is co
      precipitated with mGluR1a and that mutant Htt functions to facilitate optineurin
      mediated attenuation of mGluR1a signaling. In striatal cell lines derived from
      Htt(Q111/Q111) mutant knock-in mice mGluR5-stimulated inositol phosphate
      formation is also severely impaired when compared with striatal cells derived
      from Htt(Q7/Q7) knock-in mice. In addition, we show that a missense single
      nucleotide polymorphism optineurin H486R variant previously identified to be
      associated with glaucoma is selectively impaired in mutant Htt binding. Although
      optineurin H486R retains the capacity to bind to mGluR1a, optineurin H486R
      dependent attenuation of mGluR1a signaling is not enhanced by the expression of
      mutant Htt. Because G protein-coupled receptor kinase 2 (GRK2) protein expression
      is relatively low in striatal tissue, we propose that optineurin may substitute
      for GRK2 in the striatum to mediate mGluR desensitization. Taken together, these
      studies identify a novel mechanism for mGluR desensitization and an additional
      biochemical link between altered glutamate receptor signaling and Huntington
      disease.

PMID- 16091362
TI  - Familial Danish dementia: co-existence of Danish and Alzheimer amyloid subunits
      (ADan AND A{beta}) in the absence of compact plaques.
AB  - Familial Danish dementia is an early onset autosomal dominant neurodegenerative
      disorder linked to a genetic defect in the BRI2 gene and clinically characterized
      by dementia and ataxia. Cerebral amyloid and preamyloid deposits of two unrelated
      molecules (Danish amyloid (ADan) and beta-amyloid (Abeta)), the absence of
      compact plaques, and neurofibrillary degeneration indistinguishable from that
      observed in Alzheimer disease (AD) are the main neuropathological features of the
      disease. Biochemical analysis of extracted amyloid and preamyloid species
      indicates that as the solubility of the deposits decreases, the heterogeneity and
      complexity of the extracted peptides exponentially increase. Nonfibrillar
      deposits were mainly composed of intact ADan-(1-34) and its N-terminally modified
      (pyroglutamate) counterpart together with Abeta-(1-42) and Abeta-(4-42) in
      approximately 1:1 mixture. The post-translational modification, glutamate to
      pyroglutamate, was not present in soluble circulating ADan. In the amyloid
      fractions, ADan was heavily oligomerized and highly heterogeneous at the N and C
      terminus, and, when intact, its N terminus was post-translationally modified
      (pyroglutamate), whereas Abeta was mainly Abeta-(4-42). In all cases, the
      presence of Abeta-(X-40) was negligible, a surprising finding in view of the
      prevalence of Abeta40 in vascular deposits observed in sporadic and familial AD,
      Down syndrome, and normal aging. Whether the presence of the two amyloid subunits
      is imperative for the disease phenotype or just reflects a conformational mimicry
      remains to be elucidated; nonetheless, a specific interaction between ADan
      oligomers and Abeta molecules was demonstrated in vitro by ligand blot analysis
      using synthetic peptides. The absence of compact plaques in the presence of
      extensive neuro fibrillar degeneration strongly suggests that compact plaques,
      fundamental lesions for the diagnosis of AD, are not essential for the mechanism
      of dementia.

PMID- 16091363
TI  - Control of ASPP2/(53BP2L) protein levels by proteasomal degradation modulates p53
      apoptotic function.
AB  - The p53 pathway is a central mediator of the apoptotic response. ASPP2/(53BP2L)
      (apoptosis-stimulating protein of p53 2, also known as 53BP2L) enhances apoptosis
      through selective stimulation of p53 transactivation of proapoptotic target
      genes. Although the Rb/E2F pathway regulates ASPP2/(53BP2L) transcription, the
      complex mechanisms controlling ASPP2/(53BP2L) levels and function remain unknown.
      We now report that proteasomal degradation modulates ASPP2/(53BP2L) protein
      levels and apoptotic function. Treatment of cells with proteasomal inhibitors,
      including the clinically utilized proteasomal inhibitor bortezomib, increases
      ASPP2/(53BP2L) protein but not RNA levels. Likewise, anthracycline-based
      chemotherapy, which has multiple mechanisms of action, including proteasomal
      inhibition, increases ASPP2/(53BP2L) protein but not RNA levels. Proteasomal
      inhibition or anthracycline treatment increases ASPP2/(53BP2L) protein stability
      and half-life. Furthermore, the central region of the ASPP2/(53BP2L) protein is
      ubiquitinated as would be expected for a proteasomal substrate. More importantly,
      small interfering RNA knockdown of ASPP2/(53BP2L) levels attenuated bortezomib
      induced apoptosis, and this effect was greater in wild-type p53 cells. Because
      elevated levels of ASPP2/(53BP2L) are proapoptotic, these results described an
      important new molecular mechanism that modulates the p53-ASPP2/(53BP2L) apoptotic
      pathway.

PMID- 16091364
TI  - Selective vulnerability of dopaminergic neurons to microtubule depolymerization.
AB  - Parkinson disease (PD) is characterized by the specific degeneration of
      dopaminergic (DA) neurons in substantia nigra and has been linked to a variety of
      environmental and genetic factors. Rotenone, an environmental PD toxin, exhibited
      much greater toxicity to DA neurons in midbrain neuronal cultures than to non-DA
      neurons. The effect was significantly decreased by the microtubule-stabilizing
      drug taxol and mimicked by microtubule-depolymerizing agents such as colchicine
      or nocodazole. Microtubule depolymerization disrupted vesicular transport along
      microtubules and caused the accumulation of dopamine vesicles in the soma. This
      led to increased oxidative stress due to oxidation of cytosolic dopamine leaked
      from vesicles. Inhibition of dopamine metabolism significantly reduced rotenone
      toxicity. Thus, our results suggest that microtubule depolymerization induced by
      PD toxins such as rotenone plays a key role in the selective death of
      dopaminergic neurons.

PMID- 16091365
TI  - Chlortetracycline and demeclocycline inhibit calpains and protect mouse neurons
      against glutamate toxicity and cerebral ischemia.
AB  - Minocycline is a potent neuroprotective tetracycline in animal models of cerebral
      ischemia. We examined the protective properties of chlortetracycline (CTC) and
      demeclocycline (DMC) and showed that these two tetracyclines were also potent
      neuroprotective against glutamate-induced neuronal death in vitro and cerebral
      ischemia in vivo. However, CTC and DMC appeared to confer neuroprotection through
      a unique mechanism compared with minocycline. Rather than inhibiting microglial
      activation and caspase, CTC and DMC suppressed calpain activities. In addition,
      CTC and DMC only weakly antagonized N-methyl-D-aspartate (NMDA) receptor
      activities causing 16 and 14%, respectively, inhibition of NMDA-induced whole
      cell currents and partially blocked NMDA-induced Ca2+ influx, commonly regarded
      as the major trigger of neuronal death. In vitro and in vivo experiments
      demonstrated that the two compounds selectively inhibited the activities of
      calpain I and II activated following glutamate treatment and cerebral ischemia.
      In contrast, minocycline did not significantly inhibit calpain activity. Taken
      together, these results suggested that CTC and DMC provide neuroprotection
      through suppression of a rise in intracellular Ca2+ and inhibition of calpains.

PMID- 16091367
TI  - Tyrosine modification is not required for myeloperoxidase-induced loss of
      apolipoprotein A-I functional activities.
AB  - Apolipoprotein A-I (apoAI), the major protein of high density lipoprotein, plays
      an important role in reverse cholesterol transport via its activity as an ABCA1
      dependent acceptor of cellular cholesterol. We reported recently that
      myeloperoxidase (MPO) modification of apoAI inhibits its ABCA1-dependent
      cholesterol acceptor activity (Zheng, L., Nukuna, B., Brennan, M. L., Sun, M.,
      Goormastic, M., Settle, M., Schmitt, D., Fu, X., Thomson, L., Fox, P. L.,
      Ischiropoulos, H., Smith, J. D., Kinter, M., and Hazen, S. L. (2004) J. Clin.
      Invest. 114, 529-541). We also reported that MPO-mediated chlorination
      preferentially modifies two of the seven tyrosines in apoAI, and loss of parent
      peptides containing these residues dose-dependently correlates with loss in ABCA1
      mediated cholesterol acceptor activity (Zheng, L., Settle, M., Brubaker, G.,
      Schmitt, D., Hazen, S. L., Smith, J. D., and Kinter, M. (2005) J. Biol. Chem.
      280, 38-47). To determine whether oxidative modification of apoA-I tyrosine
      residues was responsible for the MPO-mediated inactivation of cholesterol
      acceptor activity, we made recombinant apoAI with site-specific substitutions of
      all seven tyrosine residues to phenylalanine. ApoAI and the tyrosine-free apoAI
      were equally susceptible to dose-dependent MPO-mediated loss of ABCA1-dependent
      cholesterol acceptor activity, as well as lipid binding activity. MPO
      modification altered the migration of apoAI on SDS gels and decreased its alpha
      helix content. MPO-induced modification also targeted apoAI tryptophan and lysine
      residues. Specifically, we detected apoAI tryptophan oxidation to mono- and
      dihydroxytryptophan and apoAI lysine modification to chlorolysine and 2
      aminoadipic acid. Thus, tyrosine modification of apoAI is not required for its
      MPO-mediated inhibition of cholesterol acceptor activity.

PMID- 16091366
TI  - N-linked glycosylation is required for nicotinic receptor assembly but not for
      subunit associations with calnexin.
AB  - We investigated how asparagine (N)-linked glycosylation affects assembly of
      acetylcholine receptors (AChRs) in the endoplasmic reticulum (ER). Block of N
      linked glycosylation inhibited AChR assembly whereas block of glucose trimming
      partially blocked assembly at the late stages. Removal of each of seven glycans
      had a distinct effect on AChR assembly, ranging from no effect to total loss of
      assembly. Because the chaperone calnexin (CN) associates with N-linked glycans,
      we examined CN interactions with AChR subunits. CN rapidly associates with 50% or
      more of newly synthesized AChR subunits, but not with subunits after maturation.
      Block of N-linked glycosylation or trimming did not alter CN-AChR subunit
      associations nor did subunit mutations prevent N-linked glycosylation.
      Additionally, CN associations with subunits lacking N-linked glycans occurred
      without subunit aggregation or misfolding. Our data indicate that CN associates
      with AChR subunits without N-linked glycan interactions. Furthermore, CN-subunit
      associations only occur early in AChR assembly and have no role in events later
      that require N-linked glycosylation.

PMID- 16091368
TI  - Identification of a repressor in the first intron of the human alpha2(I) collagen
      gene (COL1A2).
AB  - The human and mouse genes that code for the alpha2 chain of collagen I (COL1A2
      and Col1a2, respectively) share a common chromatin structure and nearly identical
      proximal promoter and far upstream enhancer sequences. Despite these homologies,
      species-specific differences have been reported regarding the function of
      individual cis-acting elements, such as the first intron sequence. In the present
      study, we have investigated the transcriptional contribution of the unique open
      chromatin site in the first intron of COL1A2 using a transgenic mouse model.
      DNase I footprinting identified a cluster of three distinct areas of nuclease
      protection (FI1-3) that span from nucleotides +647 to +760, relative to the
      transcription start site, and which contain consensus sequences for GATA and
      interferon regulatory factor (IRF) transcription factors. Gel mobility shift and
      chromatin immunoprecipitation assays corroborated this last finding by
      documenting binding of GATA-4 and IRF-1 and IRF-2 to the first intron sequence.
      Moreover, a short sequence encompassing the three footprints was found to inhibit
      expression of transgenic constructs containing the COL1A2 proximal promoter and
      far upstream enhancer in a position-independent manner. Mutations inserted into
      each of the footprints restored transgenic expression to different extents. These
      results therefore indicated that the unique open chromatin site of COL1A2
      corresponds to a repressor, the activity of which seems to be mediated by the
      concerted action of GATA and IRF proteins. More generally, the study reiterated
      the existence of species-specific difference in the regulatory networks of the
      mammalian alpha2(I) collagen coding genes.

PMID- 16091369
TI  - Domain 5 of high molecular weight kininogen is antibacterial.
AB  - Antimicrobial peptides are important effectors of the innate immune system. These
      peptides belong to a multifunctional group of molecules that apart from their
      antibacterial activities also interact with mammalian cells and
      glycosaminoglycans and control chemotaxis, apoptosis, and angiogenesis. Here we
      demonstrate a novel antimicrobial activity of the heparin-binding and cell
      binding domain 5 of high molecular weight kininogen. Antimicrobial epitopes of
      domain 5 were characterized by analysis of overlapping peptides. A peptide, HKH20
      (His(479)-His(498)), efficiently killed the Gram-negative bacteria Escherichia
      coli and Pseudomonas aeruginosa and the Gram-positive Enterococcus faecalis.
      Fluorescence microscopy and electron microscopy demonstrated that HKH20 binds to
      and induces breaks in bacterial membranes. Furthermore, no discernible hemolysis
      or membrane-permeabilizing effects on eukaryotic cells were noted. Proteolytic
      degradation of high molecular weight kininogen by neutrophil-derived proteases as
      well as the metalloproteinase elastase from P. aeruginosa yielded fragments
      comprising HKH20 epitopes, indicating that kininogen-derived antibacterial
      peptides are released during proteolysis.

PMID- 16091370
TI  - The binding site in {beta}2-glycoprotein I for ApoER2' on platelets is located in
      domain V.
AB  - The antiphospholipid syndrome is caused by autoantibodies directed against
      beta(2)-glycoprotein I (beta(2)GPI). Dimerization of beta(2)GPI results in an
      increased platelet deposition to collagen. We found that apolipoprotein E
      receptor 2' (apoER2'), a member of the low density lipoprotein receptor family,
      is involved in activation of platelets by dimeric beta(2)GPI. To identify which
      domain of dimeric beta(2)GPI interacts with apoER2', we have constructed domain
      deletion mutants of dimeric beta(2)GPI, lacking domain I (DeltaI), II (DeltaII),
      or V (DeltaV), and a mutant with a W316S substitution in the phospholipid (PL)
      insertion loop of domain V. DeltaI and DeltaII prolonged the clotting time, as
      did full-length dimeric beta(2)GPI; DeltaV had no effect on the clotting time.
      Second, DeltaI and DeltaII bound to anionic PL, comparable with full-length
      dimeric beta(2)GPI. DeltaV and the W316S mutant bound with decreased affinity to
      anionic PL. Platelet adhesion to collagen increased significantly when full
      length dimeric beta(2)GPI, DeltaI, or DeltaII (mean increase 150%) were added to
      whole blood. No increase was found with plasma beta(2)GPI, DeltaV, or the W316S
      mutant. Immunoprecipitation indicated that full-length dimeric beta(2)GPI,
      DeltaI, DeltaII, and the W316S mutant can interact with apoER2' on platelets.
      DeltaV did not associate with apoER2'. We conclude that domain V is involved in
      both binding beta(2)GPI to anionic PL and in interaction with apoER2' and
      subsequent activation of platelets. The binding site in beta(2)GPI for
      interaction with apoER2' does not overlap with the hydrophobic insertion loop in
      domain V.

PMID- 16091371
TI  - Analysis of the transport activity of barley sucrose transporter HvSUT1.
AB  - Localization studies indicate that barley (Hordeum vulgare) sucrose transporter
      HvSUT1 functions in sucrose uptake into seeds during grain filling. To further
      understand the physiological function of HvSUT1, we have expressed the HvSUT1
      cDNA in Xenopus laevis oocytes and analyzed the transport activity by two
      electrode voltage clamping. Consistent with a H(+)-coupled transport mechanism,
      sucrose induced large inward currents in HvSUT1-expressing oocytes with a K (0.5)
      of 3.8 mM at pH 5.0 and a membrane potential of -157 mV. Of 21 other sugars
      tested, four glucosides were also transported by HvSUT1. These glucosides were
      maltose, salicin (2-(hydroxymethyl) phenyl beta-D-glucoside), alpha
      phenylglucoside and alpha-paranitrophenylglucoside. Kinetic analysis of transport
      of these substrates by HvSUT1 was performed and K (0.5) values were measured. The
      apparent affinity for all substrates was dependent on membrane potential and pH
      with lower K (0.5) values at lower external pH and more negative membrane
      potentials. HvSUT1 was more selective for alpha-glucosides over beta-glucosides
      than the Arabidopsis sucrose transporter AtSUC2. Several substrates transported
      by AtSUC2 (beta-phenylglucoside, beta-paranitrophenylglucoside, alpha
      methylglucoside, turanose, and arbutin (hydroquinone beta-D-glucoside)) showed
      low or undetectable transport by HvSUT1. Of these, beta-paranitrophenylglucoside
      inhibited sucrose transport by HvSUT1 indicating that it interacts with the
      transporter while arbutin and alpha-methyl glucoside did not inhibit. The results
      demonstrate significant differences in substrate specificity between HvSUT1 and
      AtSUC2.

PMID- 16091372
TI  - Can rhabdomyolysis be the only cause of acute renal failure in leptospirosis?

PMID- 16091373
TI  - Vascular calcification and increased mortality in dialysis patients: Is the
      baroreflex sensitivity the answer?

PMID- 16091374
TI  - Long-term follow-up of metachronous marrow-kidney transplantation in severe type
      II sialidosis: what does success mean?

PMID- 16091375
TI  - Monoclonal antibody 1-22-3-induced glomerulonephritis in uninephrectomized rats
      as a model of progressive renal failure.
AB  - BACKGROUND: At present, there are few available animal models of progressive
      renal failure originating from mesangial proliferative glomerulonephritis (GN).
      In the current study, we examined the usefulness of anti-Thy-1 monoclonal
      antibody (mAb) 1-22-3-induced GN in uninephrectomized rats as a model of
      progressive renal failure by analysing the similarities to human disease.
      METHODS: GN was induced by intravenous injection of mAb 1-22-3 into
      uninephrectomized male Wistar rats. The natural course of the disease was
      analysed in this model for 47 weeks. The effect of treatment with the angiotensin
      converting enzyme inhibitor, captopril, on renal functional outcome was also
      examined in this model for 23 weeks, beginning from 1 week after antibody
      injection. RESULTS: Injection of mAb 1-22-3 induced a persistent proteinuria
      during the entire study period. Animals showed a progressive decline in renal
      function and 63% died by week 47. Severe glomerular and tubulointerstitial
      lesions were consistently observed. Treatment with captopril significantly
      inhibited increases in proteinuria and blood pressure, and attenuated renal
      injury. Captopril also retarded the progression of renal failure, and decreased
      mortality. Finally, the level of proteinuria was significantly correlated with
      the rate of decline in renal function, and the reduction in proteinuria by
      captopril was accompanied by a slower progression of renal failure. CONCLUSIONS:
      The mAb 1-22-3-induced GN in a uninephrectomized rat model simulates the clinical
      manifestations of human disease, indicating that this model may be useful for
      studying progressive renal failure and for investigating new therapeutic
      strategies against renal failure.

PMID- 16091376
TI  - Impact of social factors on patients on peritoneal dialysis.
AB  - BACKGROUND: Clinical outcomes among patients on peritoneal dialysis (PD) might
      not be linked to medical factors alone. We studied the clinical impact of various
      social factors among patients on PD. METHODS: In a cohort of 102 consecutive
      patients who started PD in a single centre between 2003 and 2004, we evaluated
      the effects of social factors on the development of peritonitis and risk of
      hospitalization after initiation of PD. RESULTS: Of 102 incident PD patients, 35
      subjects (34.3%) were referred to nephrologists more than 3 months before
      dialysis initiation. During 85.7 patient-years of observation (median follow-up,
      10.7 months), four subjects died and six underwent kidney transplantation.
      Patients receiving social security assistance and those younger than 40 years
      fared worse than others in terms of their risk of peritonitis. Mean peritonitis
      free time for subjects who were on social security assistance was 2.7 months, and
      for those who were not, 16.4 months (P = 0.045). In the Cox proportional hazards
      analysis, need for social security assistance and illiteracy were the only
      statistically significant factors associated with the time to a first
      peritonitis, after adjustment for social characteristics and relevant coexisting
      medical factors. Dependence on social security assistance prior to PD was
      associated with a >2-fold increased likelihood of peritonitis, with an adjusted
      risk ratio of 2.69 (95% confidence interval, 1.10 to 6.54; P = 0.029). The total
      number of hospitalization days was similar between those who received social
      security assistance and those who did not: 17.4+/-14.6 days (range, 4-50 days) vs
      17.9+/-14.0 days (range, 0-60 days) (P = 0.89). CONCLUSIONS: Our results confirm
      that socioeconomic status is closely associated with the rate of peritonitis
      among PD patients. The long-term reliability of these social predictors remains
      to be validated.

PMID- 16091377
TI  - Dose-reducing H2 receptor antagonists in the presence of low glomerular
      filtration rate: a systematic review of the evidence.
AB  - BACKGROUND: While it is recommended that H2 receptor antagonists (H2RAs) be dose
      reduced in the presence of low glomerular filtration rate (GFR), in practice such
      adjustments often do not occur. We reviewed the evidence for this recommendation.
      METHODS: We searched multiple medical reference databases for relevant cohort
      studies and randomized clinical trials. Studies that enrolled five or more
      participants with low GFR who also received at least one unadjusted dose of an
      H2RA, and who were compared with controls were included. Data were abstracted on
      study and participant characteristics and drug-related adverse effects.
      Pharmacokinetic measures were pooled using meta-analysis. RESULTS: A total of 22
      articles were included, comprising 19 unique cohort studies. With declining GFR,
      there was a significant increase in the area under the curve (AUC) and
      elimination half-life (t(1/2)) of the serum drug concentration of H2RAs (P <
      0.001). Compared with a GFR >80 ml/min/1.73 m2, drug AUC increased by 200% when
      the GFR was 30 ml/min/1.73 m2, and by 300% when the GFR was 20 ml/min/1.73 m2. In
      hospitalized patients with low GFR, reducing the interval dose of intravenous
      H2RA was associated with fewer adverse reactions. The gastro-protective effects
      of H2RAs were similar with reduced and unadjusted doses. CONCLUSIONS: Reducing
      the dose of H2RAs in persons with low GFR will decrease drug expenditure and may
      prevent adverse events, without a change in efficacy. Quality assurance
      programmes, which improve deficiencies in H2RAs prescribing, appear justified.

PMID- 16091378
TI  - A 77 year-old haemodialysis patient with unexpected alkalosis.

PMID- 16091379
TI  - Irbesartan reduces creatinine clearance in type 1 diabetic children with renal
      hyperfunction: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Previous studies in type 2 diabetes have demonstrated the
      renoprotective effect of AT(1)-receptor antagonist drugs, but data on type 1
      diabetic (T1DM) children are scarce. The aim of this study was to evaluate the
      effectiveness of the AT(1)-receptor antagonist irbesartan in reducing creatinine
      clearance rate (CCR) in non-hypertensive T1DM children with renal hyperfunction.
      METHODS: In this randomized, double-blind, placebo-controlled trial we enrolled
      20 T1DM children aged 6-16 years and randomly allocated them to receive either
      irbesartan (1 mg/kg body weight) or placebo daily for 12 weeks. Children were
      eligible to participate if they had renal hyperfunction, defined as a CCR >20
      ml/min/1.73 m(2) body surface area. In addition, the participants could not have
      high blood pressure or renal failure and they could not be receiving diuretics or
      angiotensin-converting enzyme inhibitors. The primary endpoint of the trial was
      the change in CCR. RESULTS: There were no significant differences in age,
      duration of diabetes or body mass index between the two groups. No subject
      dropped out, withdrew consent or had side effects or adverse events attributable
      to irbesartan or the placebo. In the irbesartan group, CCR decreased from 155.0+/
      6.6 to 86.2+/-7.4 ml/min (P<0.0001); CCR did not change significantly in the
      control group (154.1+/-13.1 to 172.0+/-15.5 ml/min; P = 0.86). Blood pressures at
      baseline and throughout the study were similar in both groups. CONCLUSIONS:
      Irbesartan significantly reduces CCR in non-hypertensive, non-controlled T1DM
      children; the clinical significance of this finding, however, remains to be
      established.

PMID- 16091380
TI  - QUality European STudies (QUEST)--a step forward in the quality of RRT care.

PMID- 16091381
TI  - Nutcracker phenomenon or nutcracker syndrome?

PMID- 16091382
TI  - Mortalin/GRP75 promotes release of membrane vesicles from immune attacked cells
      and protection from complement-mediated lysis.
AB  - The membrane attack complex (MAC) of the complement system is causing membrane
      damage and cell death. For protection, cells have adopted several resistance
      mechanisms, including removal of the membrane-inserted MAC by vesiculation. To
      identify proteins involved in MAC vesiculation, extracellular proteins released
      from K562 cells in response to treatment with sub-lytic complement were separated
      by acrylamide gel electrophoresis and protein bands were extracted, digested into
      peptides and the peptides were analyzed by mass spectrometry. A 75-kDa protein
      that was abundant in the supernatant of complement-treated cells was identified
      as mortalin/GRP75. Analysis by western blotting demonstrated that as early as 5
      min after exposure to sub-lytic doses of complement, mortalin was released from
      K562 cells. Mortalin was released after complete activation of the complement
      system and formation of C5b-8, and even more so when C5b-9 was formed. Other pore
      formers, such as streptolysin O and melittin, did not induce release of mortalin.
      As shown, mortalin can bind to complement C8 and C9 and is shed in vesicles
      containing C9 and complement MACs. Anti-mortalin antibodies reduced mortalin
      release from complement-treated cells and elevated the extent of cell death by
      complement. Inhibitors of protein kinase C and extracellular signal-regulated
      protein kinase also prevented mortalin release from complement-activated cells.
      These results suggest that mortalin/GRP75 promotes the shedding of membrane
      vesicles loaded with complement MAC and protects cells from complement-mediated
      lysis.

PMID- 16091383
TI  - Heterotypic interaction of CRTAM with Necl2 induces cell adhesion on activated NK
      cells and CD8+ T cells.
AB  - NK cells and CD8+ T cells exhibit cytotoxicity and cytokine production upon
      recognizing target cells through cell-cell interaction. We screened the molecules
      involved in the recognition and regulation of these cells using cDNA subtraction
      between naive and activated NK cells. We identified class I-restricted T cell
      associated molecule (CRTAM), a two Ig domain-bearing surface receptor, as a
      molecule rapidly and transiently expressed on NK cells and CD8+ T cells upon
      activation. CRTAM is expressed as a dimer on the cell surface, and its expression
      is transcriptionally regulated. Using an expression-cloning system, we then
      further identified Nectin-like (Necl) molecule 2, a three Ig domain-containing
      receptor, as a ligand of CRTAM. While Necl2 mediates homotypic interaction, CRTAM
      interacts with Necl2 but not with CRTAM itself. The heterotypic CRTAM-Necl2
      interaction has a higher affinity than the homotypic Necl2 interaction. Although
      there was no clear alteration in the cytotoxic function of the NK cells and CD8+
      T cells against the Necl2-expressing target cells, T cells expressing CRTAM
      tightly bound to Necl2-expressing cells. CRTAM+ cells did not induce homotypic
      aggregation but they did exert strong heterotypic binding with Necl2+ cells,
      which was inhibited by the addition of the CRTAM-Ig fusion protein. These results
      suggest that the heterotypic interaction between CRTAM and Necl2 plays an
      important role in the adhesion, interaction or migration of NK cells and CD8+ T
      cells upon stimulation.

PMID- 16091384
TI  - The role of suppressor of cytokine signaling 1 as a negative regulator for
      aberrant expansion of CD8alpha+ dendritic cell subset.
AB  - The suppressor of cytokine signaling (SOCS) 1 is a negative regulator in multiple
      cytokine-related aspects to maintain immunological homeostasis. Here, we studied
      a role of SOCS1 on dendritic cell (DC) maturation in the mice lacking either
      TCRalpha chain or CD28 in SOCS1-deficient background, and found that the SOCS1
      could restore acute phase of inflammatory response in SOCS1-deficient mice. The
      CD11c+ CD8- DC population in freshly isolated splenic DCs from normal mice highly
      expressed SOCS1. However, in SOCS1-deficient environment, the proportion of
      CD8alpha+ DCs (CD8 DCs) noticeably increased without affecting the cell number of
      conventional and plasmacytoid DC populations. This population revealed the
      CD11cdull CD8alpha+ CD11b- CD45RA- B220- phenotype, which is a minor population
      in normal mice. Localization of the abnormal CD8 DCs in splenic microenvironments
      was mainly restricted to deep within red pulp. The CD8 DCs secrete a large amount
      of IFN-gamma, IL-12 and B lymphocyte stimulator/B cell activation factor of the
      tumor necrosis factor family in response to LPS and CpG stimulation. This is
      responsible for the development of DC-mediated systemic autoimmunity in the old
      age of SOCS1-deficient mice. Moreover, the CD8 DC subsets expressed more
      indoleamine 2,3-dioxygenase and IL-10, and hence inhibit the allogeneic
      proliferative T cell response and antigen-induced Th1 responses. Therefore, SOCS1
      expression during DC maturation plays a role in surveillance in controlling the
      aberrant expansion of abnormal DC subset to maintain homeostasis of immune
      system.

PMID- 16091385
TI  - Impact of flow rate on lactate uptake and gluconeogenesis in glucagon-stimulated
      perfused livers.
AB  - The impact of reduced hepatic flow on lactate uptake and gluconeogenesis was
      examined in isolated glucagon-stimulated perfused livers from 24-h-fasted rats.
      After surgical isolation, livers were perfused (single pass) for 30 min with
      Krebs-Henseleit (KH) bicarbonate buffer, fresh bovine erythrocytes (hematocrit
      approximately 20%), and no added substrate. After this "washout" period, steady
      state perfusions were initiated with a second reservoir containing the KH buffer,
      bovine erythrocytes, [U-(14)C]lactate (10,000 dpm/ml), lactate (2.5 mM), and
      glucagon (250 microg/ml). Perfusion flow rate was adjusted to one of five rates
      (i.e., 1.8, 2.7, 3.9, 7.4, and 11.0 ml.min(-1).100 g body wt(-1)). After the
      perfusion, the liver was dissected out and weighed so as to establish the actual
      flow rate per gram of liver. The resulting flow rates ranged from 0.52 to 4.03
      ml.min(-1).g liver(-1). As a function of flow rate, lactate uptake rose in a
      hyperbolic fashion to an apparent plateau of 2.34 micromol.min(-1).g liver(-1).
      Fractional extraction (FX) of lactate from the perfusate demonstrated an
      exponential decline with increased flow rates (r=0.97). At flow rates above 1.0
      ml.min(-1).g liver(-1), adjustments in FX compensated for changes in lactate
      delivery, resulting in steady rates of lactate uptake and gluconeogenesis. Below
      1.0.min(-1).g liver(-1) the increased FX was unable to compensate for the decline
      in lactate delivery and lactate uptake declined rapidly. Gluconeogenesis
      demonstrated similar kinetics to lactate uptake, reflecting its dominant role
      among pathways for lactate removal under the current conditions.

PMID- 16091386
TI  - Differential effects of leptin administration on the abundance of UCP2 and
      glucocorticoid action during neonatal development.
AB  - In the neonate, adipose tissue and the lung both undergo a rapid transition after
      birth, which results in dramatic changes in uncoupling protein abundance and
      glucocorticoid action. Leptin potentially mediates some of these adaptations and
      is known to promote the loss of uncoupling protein (UCP)1, but its effects on
      other mitochondrial proteins or glucocorticoid action are not known. We therefore
      determined the effects of acute and chronic administration of ovine recombinant
      leptin on brown adipose tissue (BAT) and/or lung in neonatal sheep. For the acute
      study, eight pairs of 1-day-old lambs received, sequentially, 10, 100, and 100
      mug of leptin or vehicle before tissue sampling 4 h from the start of the study,
      whereas in the chronic study, nine pairs of 1-day-old lambs received 100 mug of
      leptin or vehicle daily for 6 days before tissue sampling on day 7. Acute leptin
      decreased the abundance of UCP2, glucocorticoid receptor, and 11beta
      hydroxysteroid dehydrogenase (11beta-HSD) type 1 mRNA and increased 11beta-HSD
      type 2 mRNA abundance in BAT, a pattern that was reversed with chronic leptin
      administration, which also diminished lung UCP2 protein abundance. In BAT, UCP2
      mRNA abundance was positively correlated to plasma leptin and nonesterified fatty
      acids and negatively correlated to mean colonic temperature in the leptin group
      at 7 days. In conclusion, leptin administration to the neonatal lambs causes
      differential effects on UCP2 abundance in BAT and lung. These effects may be
      important in the development of these tissues, thereby optimizing lung function
      and fat growth.

PMID- 16091387
TI  - Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and
      adipocytes.
AB  - Intracellular lipolysis is a major pathway of lipid metabolism that has roles,
      not only in the provision of free fatty acids as energy substrate, but also in
      intracellular signal transduction. The latter is likely to be particularly
      important in the regulation of insulin secretion from islet beta-cells. The
      mechanisms by which lipolysis is regulated in different tissues is, therefore, of
      considerable interest. Here, the effects of long-chain acyl-CoA esters (LC-CoA)
      on lipase activity in islets and adipocytes were compared. Palmitoyl-CoA (Pal
      CoA, 1-10 microM) stimulated lipase activity in islets from both normal and
      hormone-sensitive lipase (HSL)-null mice and in phosphatase-treated islets,
      indicating that the stimulatory effect was neither on HSL nor phosphorylation
      dependent. In contrast, we reproduced the previously published observations
      showing inhibition of HSL activity by LC-CoA in adipocytes. The inhibitory effect
      of LC-CoA on adipocyte HSL was dependent on phosphorylation and enhanced by acyl
      CoA-binding protein (ACBP). In contrast, the stimulatory effect on islet lipase
      activity was blocked by ACBP, presumably due to binding and sequestration of LC
      CoA. These data suggest the following intertissue relationship between islets and
      adipocytes with respect to fatty acid metabolism, LC-CoA signaling, and
      lipolysis. Elevated LC-CoA in islets stimulates lipolysis to generate a signal to
      increase insulin secretion, whereas elevated LC-CoA in adipocytes inhibits
      lipolysis. Together, these opposite actions of LC-CoA lower circulating fat by
      inhibiting its release from adipocytes and promoting fat storage via insulin
      action.

PMID- 16091388
TI  - Method for the determination of the arteriovenous muscle protein balance during
      non-steady-state blood and muscle amino acid concentrations.
AB  - We describe a method based on the traditional arteriovenous balance technique in
      conjunction with muscle biopsies for the determination of leg muscle protein
      balance during the nonsteady state in blood amino acid concentrations. Six young,
      healthy individuals were studied in the postabsorptive state (pre-Phe) and after
      a bolus ingestion of approximately 0.5 g phenylalanine (post-Phe). Post-Phe free
      phenylalanine concentrations in blood and muscle increased (P < 0.05), but the
      respective concentrations of the amino acid threonine did not change. The average
      post-Phe leg net balance (NB) for threonine decreased from basal (P < 0.05), but
      that for phenylalanine did not change. A volume of distribution for free
      phenylalanine in the leg was calculated based on the leg lean mass and the
      relative muscle water content and used to estimate the rate of accumulation of
      free phenylalanine in the leg. When the post-Phe NB for phenylalanine was
      corrected for the rate of accumulation of free phenylalanine in the leg, the post
      Phe NB for phenylalanine decreased from basal (P < 0.05). This corrected value
      was not different (P > 0.05) from the value predicted for the phenylalanine NB
      based on the pre- and post-Phe NB responses for threonine. We conclude that the
      protein NB in non-steady-state blood phenylalanine concentrations can be
      determined from the arteriovenous phenylalanine NB by accounting for changes in
      free phenylalanine within its volume of distribution.

PMID- 16091389
TI  - Sex-based physiology prior to political correctness.

PMID- 16091390
TI  - Adrenocortical function, feedback, and alphabet soup.

PMID- 16091391
TI  - Estimation of dose-response curves and identification of peaks in hormone
      pulsations: classic marriages of statistics to science.

PMID- 16091392
TI  - Interpreting the overall metabolic consequences of exercise in diabetes.

PMID- 16091393
TI  - Systemic sclerosis, morphoea and breast cancer.

PMID- 16091394
TI  - The economic burden of disabling hip and knee osteoarthritis (OA) from the
      perspective of individuals living with this condition.
AB  - OBJECTIVE: To estimate the direct and indirect arthritis-attributable costs to
      individuals with disabling hip and/or knee osteoarthritis (OA). METHODS: An
      established population cohort with disabling hip and/or knee OA from two regions
      of Ontario, Canada was surveyed to determine participant and caregiver costs
      related to OA, and the predictors of these costs. RESULTS: The response rate was
      87.2%. Of 1378 respondents, 1258 had OA (mean age 73.1 yr, range 59-100). Sixty
      per cent (n = 758) reported OA-related costs. Among these individuals, the
      average annual cost was 12,200 dollars(CDN dollars in 2002, where 1.00 CDN dollar
      approximately 0.81 US dollar). Time lost from employment and leisure by
      participants and their unpaid caregivers accounted for 80% of the total. Men were
      less likely than women to report costs (adjusted odds ratio 0.54, P < 0.0001),
      but when they did their expenditures were significantly higher (P = 0.004).
      Greater disability was associated with higher costs: compared with individuals
      with WOMAC total scores <15, those with scores > or = 55 were 15 times more
      likely to report costs, and their costs were 3 times greater (both P < 0.0001).
      Both the young (<65 yr) and very old were more likely to incur costs (P <
      0.0001), and when they did their costs were higher (P < 0.001). CONCLUSION: Costs
      incurred were mainly for time lost from employment and leisure, and for unpaid
      informal caregivers. Failure to value such indirect costs significantly
      underestimates the true burden of OA. Costs increased with worsening health
      status and greater OA severity. After adjustment, men were less likely to incur
      costs, possibly due to greater social resources.

PMID- 16091395
TI  - The current concept of spondyloarthritis with special emphasis on
      undifferentiated spondyloarthritis.

PMID- 16091396
TI  - Persistent reduction of spinal inflammation as assessed by magnetic resonance
      imaging in patients with ankylosing spondylitis after 2 yrs of treatment with the
      anti-tumour necrosis factor agent infliximab.
AB  - OBJECTIVES: Patients with ankylosing spondylitis (AS) benefit from anti-TNF
      therapy both on a clinical basis and as depicted by magnetic resonance imaging
      (MRI). It is not known whether spinal inflammation remains suppressed over time.
      Our objective was to assess spinal inflammation by MRI in AS patients after 2 yr
      of continuous infliximab treatment. METHODS: Twenty patients with active AS were
      examined by MRI at baseline, after 3 months (end of placebo-controlled-phase) and
      after 2 yr of continuous infliximab therapy (5 mg/kg/6 weeks). T1 pre- and post
      gadolinium (T1/gadolinium-diethylenetriamine-pentaacetic acid) and short tau
      inversion recovery (STIR) MRI sequences were performed and read by one blinded
      reader using the ASspiMRI score. RESULTS: Spinal inflammation, detected by MRI in
      all patients at baseline, decreased after 3 months only in the infliximab group
      in both MRI sequences. Persistent improvement of spinal inflammation was seen
      after 2 yr by scoring STIR sequences, with a mean score of 4.6 +/- 5.9 vs 15.2 +/
      13.2 at baseline (P = 0.01). On an individual level, inflammatory spinal lesions
      decreased from 6.7 +/- 5.0 per patient at baseline to 2.2 +/- 1.8 after 2 yr (P =
      0.003). Improvement in spinal inflammation was found in all patients by both MRI
      sequences. Only a minor degree but some spinal inflammation was still present
      after 2 yrs. CONCLUSION: Spinal inflammation in MRI was persistently reduced in
      all patients constantly treated with infliximab, but it was not completely
      eradicated. Disease activity parameters did not directly correlate with MRI, but
      both pointed in the same direction. Both types of information may be useful for
      the definition of response to anti-TNF therapy.

PMID- 16091397
TI  - Reading radiographs in pairs or in chronological order influences radiological
      progression in osteoarthritis.
AB  - OBJECTIVE: To determine the influence of the order in which a series of
      radiographs were read on the sensitivity to change over a 2-yr follow-up period
      in patients with osteoarthritis (OA) at multiple sites. METHODS: Radiographs of
      20 patients with OA in at least two joint sites were obtained at baseline and
      after 2 yr, and scored according to the consensus of two readers. Joint space
      narrowing (JSN) and osteophytes were graded (0-3) in the hand, hip and
      tibiofemoral joints. The cervical (C2-7) and lumbar spine disc spaces (L1-S1)
      were graded (0-3) for disc space narrowing (DSN) and anterior osteophytes. Films
      were read by two different procedures: in pairs, with an unknown time sequence
      and in chronological order. Radiological progression was defined as an increase
      of at least one grade in JSN, DSN or osteophyte total scores. The two procedures
      were compared using standardized response means (SRM). RESULTS: The SRM for
      changes in JSN or DSN progression scores in the hands, hips, knees and spine
      were, respectively, 0.00, 0.00, 0.32, 0.13 and 0.38, 0.32, 0.56, 0.18 for the
      paired and chronological readings. The SRM for changes in osteophyte progression
      scores in the hands, hips, knees and spine were, respectively, 0.39, 0.20, 0.32,
      0.38 and 0.41, 0.37, 0.56, 0.66 for the paired and chronological readings.
      CONCLUSION: When assessing radiological progression in OA, reading a series of
      radiographs in chronological order tended to be more sensitive to change over a 2
      yr follow-up period than reading in pairs with an unknown time sequence.

PMID- 16091398
TI  - A cost consequences analysis of local corticosteroid injection and physiotherapy
      for the treatment of new episodes of unilateral shoulder pain in primary care.
AB  - OBJECTIVE: Local steroid injections and community-based physiotherapy have been
      shown to be of similar benefit for treating shoulder pain presenting to primary
      care. This paper presents a cost consequences analysis of a prospective economic
      evaluation, conducted alongside a randomized clinical trial (RCT) of
      corticosteroid injections versus physiotherapy for new episodes of unilateral
      shoulder pain, to determine the economic implications of injection versus
      physiotherapy. METHODS: A pragmatic RCT with 207 patients randomized to either
      physiotherapy (n = 103) or local steroid injection (n = 104) was conducted. The
      resource inputs required were identified for each treatment arm in terms of
      capital, staff and consumables. These were measured for the period up to 6 months
      post-randomization. Outcome measures included shoulder disability, shoulder pain,
      global assessment of health change and the EQ5D, all at 6 months. A sensitivity
      analysis was performed around the general practitioner minor surgical fee.
      RESULTS: Analysis is presented on the 199 patients for which the general practice
      record review (101 physiotherapy, 98 injection) was available. The total mean
      costs, per patient, were 71.28 pound sterling for the injection group and 114.60
      pound sterling for the physiotherapy group. The difference in average total cost
      per patient was 43.32 pound sterling (95% bootstrap confidence interval: 16.21
      pound sterling, 68.03 pound sterling ). This is a statistically significant
      difference in cost. Outcome was similar in both groups across all measures
      following intervention. Smaller mean differences in cost were observed between
      the treatment groups in the sensitivity analysis, but the difference remained in
      favour of injection over physiotherapy. CONCLUSIONS: This study has shown, given
      similar clinical outcomes across the treatment groups, that corticosteroid
      injections were the cost-effective option for patients presenting with new
      episodes of unilateral shoulder pain in primary care.

PMID- 16091399
TI  - Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies
      to Escherichia coli are associated with early rheumatoid factor (RF)-positive
      rheumatoid arthritis.
AB  - OBJECTIVE: Antibodies to Proteus mirabilis were previously detected in patients
      with established rheumatoid arthritis (RA). We examined the prevalence of
      antibodies to P. mirabilis and their associations with RA in early synovitis
      patients. METHODS: Two hundred and forty-six patients with inflammatory arthritis
      for less than 1 yr were prospectively evaluated for 1 yr. Of these patients, 30%
      had rheumatoid factor (RF)-positive RA, 16% RF-negative RA, 17% a
      spondyloarthropathy and 37% undifferentiated arthritis. Serum antibodies to P.
      mirabilis, Escherichia coli and other potentially arthritogenic organisms
      (Chlamydia, Salmonella, Shigella, Campylobacter, Yersinia and parvovirus B19) and
      for antibodies specific for immunoglobulin (Ig) G damaged with advanced glycation
      end-products (anti-IgG-AGE) were measured. RESULTS: IgM and IgA anti-Proteus
      antibodies were significantly higher in patients with RF-positive RA compared
      with all other patient groups (P < 0.0005 and P < 0.005). Anti-P. mirabilis IgG,
      and IgG, IgA, and IgM antibodies to other potentially arthritogenic pathogens did
      not differ in the patient groups. IgM antibodies to E. coli were elevated in RF
      positive RA patients. Anti-P. mirabilis IgM and IgA results were not explained by
      false-positive reactions, because after absorption of RF there was no decrease in
      antibodies to Proteus in 10 of 12 patients. Proteus and E. coli antibodies were
      highest in patients positive for both RF and anti-IgG-AGE antibodies (P<0.001).
      Patients with erosions tended to have higher IgA anti-Proteus titres, but no
      association with the shared HLA epitope or treatment was detected. CONCLUSION:
      Anti-P. mirabilis IgM and IgA and anti-E. coli IgM antibody elevations are
      associated with early seropositive RA and the presence of anti-IgG-AGE
      antibodies. The role that P. mirabilis or E. coli plays in early RF-positive RA
      requires further investigation.

PMID- 16091400
TI  - Optimisation of a secondary standard chamber for the measurement of the ambient
      dose equivalent, H*(10), for low photon energies.
AB  - A secondary standard ionisation chamber for photon radiation for measuring an
      ionisation current, which is directly proportional to the conventionally true
      value of the ambient dose equivalent, H*(10), was optimised. The chamber was
      developed in the Austrian Research Centers Seibersdorf and is used successfully
      worldwide by dosimetry laboratories. The chamber response with respect to H*(10)
      for photon energies from 40 to 1,250 keV is nearly constant. For lower photon
      energies the response is strongly energy-dependent and does not fulfil the
      requirements concerning the quality of a secondary standard given in ISO 4,037-2,
      i.e. for energies for which the determination of the conventionally true value of
      H*(10) is very difficult. Considering the dose limits defined in the Directive
      96/29/Euratom, in the case of whole-body irradiation the knowledge of the
      personal dose equivalent is of importance down to energies of approximately 12
      keV. For area dosimetry, this means that the knowledge of H*(10) for energies
      approximately >or=12 keV is necessary. To get one secondary standard chamber for
      H*(10) for the whole photon energy range and to close the gap for low energies in
      the dissemination of the conventionally true value of H*(10), the chamber was
      optimised for a flat response for energies from approximately 12 to 1,250 keV.

PMID- 16091401
TI  - Calibration of an electrostatic chamber for thoron measurements in exhaled
      breath.
AB  - An electrostatic chamber system used for measuring thoron in the exhaled breath
      of thorium workers is calibrated using a standard thoron source and a
      scintillation cell counting system. A formulation based on both a streamlined
      flow model and a well-mixed flow model in the chamber has been made to estimate
      thoron concentration in breath from the observed alpha counts. The experimental
      measurements of the ratio of the outlet and the inlet thoron concentrations
      across the chamber strongly validate the well-mixed flow model for thoron, as
      against the streamlined flow model. The progeny collection efficiency on the
      electrode has been found to be 70%. The study points out a major error by a
      factor of approximately 25 in the calibration factor reported in an earlier work.
      From the present study, the minimum detectable limit of the activity of (224)Ra,
      freely emanating thoron at mouth works out to be 0.36 Bq as against 0.014 Bq
      reported earlier for the same system.

PMID- 16091402
TI  - New dimensions in tissue engineering: possible models for human physiology.
AB  - Tissue engineering is a discipline of great promise. In some areas, such as the
      cornea, tissues engineered in the laboratory are already in clinical use. In
      other areas, where the tissue architecture is more complex, there are a number of
      obstacles to manoeuvre before clinically relevant tissues can be produced.
      However, even in areas where clinically relevant tissues are decades away, the
      tissues being produced at the moment provide powerful new models to aid the
      understanding of complex physiological processes. This article provides a
      personal view of the role of tissue engineering in advancing our understanding of
      physiology, with specific attention being paid to musculoskeletal tissues.

PMID- 16091403
TI  - Long-term effects of streptozotocin-induced diabetes on the electrocardiogram,
      physical activity and body temperature in rats.
AB  - In vivo biotelemetry studies have demonstrated that short-term streptozotocin
      (STZ)-induced diabetes is associated with a reduction in heart rate (HR) and
      heart rate variability (HRV) and prolongation of QT and QRS intervals. This study
      investigates the long-term effects of STZ-induced diabetes on the
      electrocardiogram (ECG), physical activity and body temperature. Transmitter
      devices were surgically implanted in the peritoneal cavity of young adult male
      Wistar rats. Electrodes from the transmitter were arranged in Einthoven bipolar
      lead II configuration. ECG, physical activity and body temperature data were
      continuously recorded with a telemetry system before and following the
      administration of STZ (60 mg kg(-1)) for a period of 22 weeks. HR, physical
      activity and body temperature declined rapidly 3-5 days after the administration
      of STZ. The effects became conspicuous with time reaching a new steady state
      approximately 1-2 weeks after STZ treatment. HR at 4 weeks was 268 +/- 5 beats
      min(-1) in diabetic rats compared to 347 +/- 12 beats min(-1) in age-matched
      controls. HRV at 4 weeks was also significantly reduced after STZ treatment (18
      +/- 3 beats min(-1)) compared to controls (33 +/- 3 beats min(-1)). HR and HRV
      were not additionally altered in either diabetic rats (266 +/- 5 and 20 +/- 4
      beats min(-1)) or age-matched controls (316 +/- 6 and 25 +/- 4 beats min(-1)) at
      22 weeks. Reduced physical activity and/or body temperature may partly underlie
      the reductions in HR and HRV. In addition, the increased power spectral low
      frequency/high frequency ratio from 4 weeks after STZ treatment may indicate an
      accompanying disturbance in sympathovagal balance.

PMID- 16091404
TI  - Dose-dependent systemic and renal haemodynamic effects of angiotensin II in
      conscious lambs: role of angiotensin AT1 and AT2 receptors.
AB  - The present experiments were designed to measure the effects of acute
      administration of angiotensin (ANG) II on mean arterial pressure (MAP) and renal
      blood flow (RBF) in conscious, chronically instrumented lambs at two different
      stages of postnatal maturation, and to determine the receptors through which
      these effects of ANG II are elicited. Experiments consisted of haemodynamic
      measurements for 10 s before (Control) and for 60 s after intravenous (i.v.)
      administration of one of 11 doses of ANG II (0-200 ng kg(-1)). Administration of
      ANG II was associated with a dose-dependent increase in MAP to a maximal
      effective concentration (EC100) of 100 ng kg(-1) in lambs aged 1 and 6 weeks.
      Administration of ANG II has caused a dose-dependent decrease in RBF, with EC100
      values of 50 ng kg(-1) in 1-week-old lambs, and 25 ng kg(-1) in 6-week-old lambs.
      Responses to ANG II at the EC(50) were also measured in the presence of the
      specific ANG II AT(1) receptor antagonist, ZD 7155, the specific AT2 receptor
      antagonist, PD 123319, and vehicle. Administration of ZD 7155, but not PD 123319
      or vehicle, abolished the MAP and RBF responses to ANG II in both age groups. In
      addition, MAP decreased and RBF increased in both age groups after administration
      of ZD 7155, but not PD 123319; the effects were similar in both age groups. These
      data provide new information that pressor and renal vasoconstrictor effects of
      ANG II during the first 6 weeks of postnatal life in lambs are elicited by
      activation of AT1 but not AT2 receptors.

PMID- 16091405
TI  - CNS-induced natriuresis, neurohypophyseal peptides and renal dopamine and
      noradrenaline excretion in prehypertensive salt-sensitive Dahl rats.
AB  - To identify defects in the salt-sensitive Dahl rat (Dahl-S), the natriuretic,
      catecholaminergic and pressor responses to 60-min elevation of the
      cerebroventricular sodium concentration (CNS-induced natriuresis) were compared
      between prehypertensive salt-sensitive Dahl-S and salt-resistant Dahl rats (Dahl
      R). The plasma concentrations of the rat natriuretic hormone oxytocin, which has
      implications for the development of hypertension, and vasopressin (AVP) were also
      measured. Basal sodium and catecholamine excretion and mean arterial blood
      pressure (MAP) were similar in both strains. Sodium excretion during CNS
      stimulation increased more than 15-fold in Dahl-R but only 10-fold in Dahl-S.
      Dopamine excretion increased only transiently and similarly in both strains.
      Noradrenaline excretion and response to CNS stimulation were similar, suggesting
      a comparable sympathetic nervous activity between the strains. MAP increased
      comparably in Dahl-R and Dahl-S. Plasma AVP concentration was similar in both
      strains while plasma oxytocin concentration after CNS stimulation was more than 2
      fold higher in Dahl-S than in Dahl-R. In conclusion, the prehypertensive Dahl-S
      has an attenuated natriuretic response to elevations of the cerebroventricular
      fluid sodium concentration and a higher plasma level of the natriuretic hormone
      oxytocin. Dopamine is not a mediator of CNS-induced natriuresis in neither
      strain. The attenuated natriuretic response may partly explain the salt
      sensitivity in Dahl-S, and the higher plasma oxytocin value may either represent
      an effort to compensate for the deficient natriuretic response or reflect a
      primary defect in this system. Due to the known involvement of oxytocin in
      central MAP regulation in some hypertensive animal models, the findings warrant
      further investigation.

PMID- 16091406
TI  - Specialty versus community hospitals: what role for the law?
AB  - U.S. health care has long featured a struggle between regulation and markets as
      vehicles of reform, and the community hospital is at the center of this struggle.
      The key to its financial viability is cross-subsidization, whereby revenues from
      insured patients subsidize the care of the uninsured and underinsured, and
      profits from well-compensated services support those operating at a loss. Cross
      subsidization has been challenged by efforts to move highly compensated services
      and well-insured patients to ambulatory surgical centers and specialty hospitals.
      We review the ongoing battle between through a legal lens and offer conjectures
      about the outcome. Refined certificate-of-need regulation may be the preferable
      policy choice.

PMID- 16091407
TI  - Monopoly is not the answer.
AB  - Certificate-of-need (CON) regulation was originally intended to correct market
      failures that no longer afflict health care markets. It is ironic that Sujit
      Choudhry and colleagues now invoke it to deal with situations where, in their
      view, competition is working altogether too well. Protectionist regulation, long
      discredited in other areas, is particularly misguided in health care, where
      health insurance greatly increases the profitability of monopoly and imposes the
      resulting higher costs on unwilling premium payers. To use cross-subsidies to
      finance even worthy (let alone unworthy) health care projects is to put public
      burdens unfairly (regressively) on the backs of working Americans.

PMID- 16091408
TI  - When the price isn't right: how inadvertent payment incentives drive medical
      care.
AB  - Unintended overpayment of some services, in combination with other market
      factors, is driving increased use of expensive care, which in turn could be an
      important driver of health care cost trends. Reimbursement systems are highly
      dependent on provider charge data that rarely provide accurate and up-to-date
      indicators of relative costs. As a result, newer services, in which productivity
      is increasing over time, tend to be more lucrative. As the largest payer, and one
      whose reimbursement policies are followed by private insurers and Medicaid
      programs, Medicare can address this issue by taking steps to make its prospective
      payment rates reflect relative costs more accurately.

PMID- 16091409
TI  - Accounting for probe-level noise in principal component analysis of microarray
      data.
AB  - MOTIVATION: Principal Component Analysis (PCA) is one of the most popular
      dimensionality reduction techniques for the analysis of high-dimensional
      datasets. However, in its standard form, it does not take into account any error
      measures associated with the data points beyond a standard spherical noise. This
      indiscriminate nature provides one of its main weaknesses when applied to
      biological data with inherently large variability, such as expression levels
      measured with microarrays. Methods now exist for extracting credibility intervals
      from the probe-level analysis of cDNA and oligonucleotide microarray experiments.
      These credibility intervals are gene and experiment specific, and can be
      propagated through an appropriate probabilistic downstream analysis. RESULTS: We
      propose a new model-based approach to PCA that takes into account the variances
      associated with each gene in each experiment. We develop an efficient EM
      algorithm to estimate the parameters of our new model. The model provides
      significantly better results than standard PCA, while remaining computationally
      reasonable. We show how the model can be used to 'denoise' a microarray dataset
      leading to improved expression profiles and tighter clustering across profiles.
      The probabilistic nature of the model means that the correct number of principal
      components is automatically obtained.

PMID- 16091410
TI  - A hybrid machine-learning approach for segmentation of protein localization data.
AB  - MOTIVATION: Subcellular protein localization data are critical to the
      quantitative understanding of cellular function and regulation. Such data are
      acquired via observation and quantitative analysis of fluorescently labeled
      proteins in living cells. Differentiation of labeled protein from cellular
      artifacts remains an obstacle to accurate quantification. We have developed a
      novel hybrid machine-learning-based method to differentiate signal from artifact
      in membrane protein localization data by deriving positional information via
      surface fitting and combining this with fluorescence-intensity-based data to
      generate input for a support vector machine. RESULTS: We have employed this
      classifier to analyze signaling protein localization in T-cell activation. Our
      classifier displayed increased performance over previously available techniques,
      exhibiting both flexibility and adaptability: training on heterogeneous data
      yielded a general classifier with good overall performance; training on more
      specific data yielded an extremely high-performance specific classifier. We also
      demonstrate accurate automated learning utilizing additional experimental data.

PMID- 16091411
TI  - ProRule: a new database containing functional and structural information on
      PROSITE profiles.
AB  - MOTIVATION: Increase the discriminatory power of PROSITE profiles to facilitate
      function determination and provide biologically relevant information about
      domains detected by profiles for the annotation of proteins. SUMMARY: We have
      created a new database, ProRule, which contains additional information about
      PROSITE profiles. ProRule contains notably the position of structurally and/or
      functionally critical amino acids, as well as the condition they must fulfill to
      play their biological role. These supplementary data should help function
      determination and annotation of the UniProt Swiss-Prot knowledgebase. ProRule
      also contains information about the domain detected by the profile in the Swiss
      Prot line format. Hence, ProRule can be used to make Swiss-Prot annotation more
      homogeneous and consistent. The format of ProRule can be extended to provide
      information about combination of domains. AVAILABILITY: ProRule can be accessed
      through ScanProsite at http://www.expasy.org/tools/scanprosite. A file containing
      the rules will be made available under the PROSITE copyright conditions on our
      ftp site (ftp://www.expasy.org/databases/prosite/) by the next PROSITE release.

PMID- 16091412
TI  - Assessing the application of Ka/Ks ratio test to alternatively spliced exons.
AB  - SUMMARY: Recently, the Ka/Ks ratio test, which assesses the protein-coding
      potentials of genomic regions based on their non-synonymous to synonymous
      divergence rates, has been proposed and successfully used in genome annotations
      of eukaryotes. We systematically performed the Ka/Ks ratio test on 925 transcript
      confirmed alternatively spliced exons in the human genome, which we describe in
      this manuscript. We found that 22.3% of evolutionarily conserved alternatively
      spliced exons cannot pass the Ka/Ks ratio test, compared with 9.8% for
      constitutive exons. The false negative rate was the highest (85.7%) for exons
      with low frequencies of transcript inclusion. Analyses of alternatively spliced
      exons supported by full-length mRNA sequences yielded similar results, and nearly
      half of exons involved in ancestral alternative splicing events could not pass
      this test. Our analysis suggests a future direction to incorporate comparative
      genomics-based alternative splicing predictions with the Ka/Ks ratio test in
      higher eukaryotes with extensive RNA alternative splicing.

PMID- 16091413
TI  - Statistical challenges in the analysis of two-dimensional difference gel
      electrophoresis experiments using DeCyder.
AB  - MOTIVATION: The DeCyder software (GE Healthcare) is the current state-of-the-art
      commercial product for the analysis of two-dimensional difference gel
      electrophoresis (2D DIGE) experiments. Analyses complementing DeCyder are
      suggested by incorporating recent advances from the microarray data analysis
      literature. A case study on the effect of smallpox vaccination is used to compare
      the results obtained from DeCyder with the results obtained by applying moderated
      t-tests adjusted for multiple comparisons to DeCyder output data that was
      additionally normalized. RESULTS: Application of the more stringent statistical
      tests applied to the normalized 2D DIGE data decreased the number of potentially
      differentially expressed proteins from the number obtained from DeCyder and
      increased the confidence in detecting differential expression in human clinical
      studies.

PMID- 16091414
TI  - Two-stage designs for experiments with a large number of hypotheses.
AB  - MOTIVATION: When a large number of hypotheses are investigated the false
      discovery rate (FDR) is commonly applied in gene expression analysis or gene
      association studies. Conventional single-stage designs may lack power due to low
      sample sizes for the individual hypotheses. We propose two-stage designs where
      the first stage is used to screen the 'promising' hypotheses which are further
      investigated at the second stage with an increased sample size. A multiple test
      procedure based on sequential individual P-values is proposed to control the FDR
      for the case of independent normal distributions with known variance. RESULTS:
      The power of optimal two-stage designs is impressively larger than the power of
      the corresponding single-stage design with equal costs. Extensions to the case of
      unknown variances and correlated test statistics are investigated by simulations.
      Moreover, it is shown that the simple multiple test procedure using first stage
      data for screening purposes and deriving the test decisions only from second
      stage data is a very powerful option.

PMID- 16091415
TI  - Sense and antisense transcripts of the apolipoprotein E gene in normal and ApoE
      knockout mice, their expression after spinal cord injury and corresponding human
      transcripts.
AB  - The apolipoprotein E (ApoE) gene has been linked to maladies such as
      hypercholesterolemia, CNS injury and disease. In this study, we present evidence
      that, in addition to the known transcript (ApoE S1) that translates into ApoE,
      there are three additional transcripts in mice. Two of these transcripts, ApoE S2
      and ApoE S3, which are predicted to be transmembrane proteins, are transcribed
      from the sense strand. ApoE AS1 is transcribed from the antisense strand and is
      complementary to exon 4 of ApoE S1. The open reading frame of ApoE AS1 is
      conserved between human and mouse. The antisense transcript falls within the
      region of the human epsilon 4 allele that has been linked to the familial onset
      form of Alzheimer's disease. We also demonstrate the expression of ApoE S3 and
      ApoE AS1 in ApoE knockout mice, and ApoE S1 and ApoE S2 do not get transcribed.
      We had previously identified ApoE S1 as being upregulated in mice after spinal
      cord injury. In this study, we show that in spinal cord-injured C57BL/6 mice,
      both ApoE S1 and ApoE S3 transcripts are 10-fold upregulated and the antisense
      ApoE AS1 is 100-fold upregulated compared with normal levels. Such data suggest
      that these alternate transcripts are involved in the molecular pathogenesis of
      CNS disease and perhaps in ApoE expression in general, as we show that ApoE S2
      and AS1 are also transcribed in human.

PMID- 16091416
TI  - 70/30 insulin algorithm versus sliding scale insulin.
AB  - BACKGROUND: The medical literature supports the fact that sliding scale dosing of
      insulin is an ineffective means to control blood glucose concentrations. Despite
      this, many clinicians still use sliding scale insulin (SSI) regimens. A better
      tool for controlling hyperglycemia is clearly needed. OBJECTIVE: To compare the
      efficacy of an algorithm using 70/30 insulin with traditional SSI dosing for
      glycemic control in hospitalized patients with type 2 diabetes. METHODS: A
      prospective, cohort, comparative trial was conducted at a 644-bed, 2-hospital,
      regional referral health system. Patients were screened for enrollment based on
      orders received in the pharmacy for sliding scale dosing of insulin. Patients
      were treated either following an algorithm using 70/30 insulin twice daily or
      traditional SSI dosing as written by the prescribing physician. RESULTS: Twenty
      patients with type 2 diabetes were involved in this pilot trial: 10 were treated
      with the 70/30 insulin algorithm and 10 received a physician-determined
      traditional SSI regimen. Patients treated based on the 70/30 insulin algorithm
      achieved better glycemic control (p = 0.042). No difference between the groups
      was detected in the average number of insulin units administered, insulin
      injections, or days patients spent on their respective insulin regimens.
      CONCLUSIONS: Glycemic control with the 70/30 insulin algorithm was superior to
      traditional SSI dosing.

PMID- 16091417
TI  - Antidepressant-induced adverse reactions in a patient with hemorrhagic stroke.
AB  - OBJECTIVE: To report a case of antidepressant-induced adverse drug reactions in a
      patient with hemorrhagic stroke. CASE SUMMARY: A 56-year-old man developed life
      threatening adverse reactions after fluoxetine was added to his previously
      prescribed regimen of buspirone and olanzapine. One week after starting
      fluoxetine 60 mg/day, the patient developed syndrome of inappropriate
      antidiuretic hormone secretion and serotonin syndrome concurrently. The patient
      had experienced a hemorrhagic stroke before the adverse drug reactions occurred.
      DISCUSSION: A patient with a history of hemorrhagic stroke developed serious
      adverse drug reactions when fluoxetine was added to his drug therapy. When the
      combination therapy was stopped, all adverse effects gradually disappeared and
      laboratory abnormalities were corrected. The likelihood that the adverse
      reactions were caused by fluoxetine is probable according to the Naranjo
      probability scale. In addition, a history of stroke may be a risk factor for the
      development of such reactions. CONCLUSIONS: Today, patients with depression after
      experiencing a stroke are treated more effectively, but antidepressant-induced
      adverse drug reactions may be serious. A growing number of patients are treated
      for post-stroke depression; they require close supervision and careful dosing of
      antidepressants to prevent full-blown adverse reactions from occurring.

PMID- 16091418
TI  - Temporal gene expression profiling of liver from periparturient dairy cows
      reveals complex adaptive mechanisms in hepatic function.
AB  - Long-term molecular adaptations in liver from high-producing dairy cows are
      virtually unknown. Liver from five Holstein cows was biopsied at -65, -30, -14,
      +1, +14, +28, and +49 days relative to parturition for transcript profiling using
      a microarray consisting of 7,872 annotated cattle cDNA inserts. More than 5,000
      cDNA elements represented on the microarray were expressed in liver. From this
      set we identified 62 differentially expressed genes related to physiological
      state, with a false discovery rate threshold of P = 0.20. The dominant expression
      pattern consisted of upregulation from day -30 through day +1, followed by
      downregulation through day +28. There was a threefold decrease from day -65
      through day +14 in expression of IGFBP3, GSTM5, and PDPK1. These genes mediate
      IGF-I transport, oxidative stress, and glucose homeostasis, respectively. IGFBP3,
      EIF4B, and GSTM5 mRNA levels were positively correlated with blood serum total
      protein. Correlation analysis showed positive associations between serum
      nonesterified fatty acids and mRNA expression for SAA1, CPT1A, ACADVL, and
      TFAP2A. Transcript levels of ACSL1, PPARA, and TFAP2A were positively correlated
      with serum beta-hydroxybutyrate. Expression patterns for certain genes (e.g.,
      IGFBP3, HNF4A, GPAM) revealed adaptations commencing well ahead of parturition,
      suggesting they are regulated by factors other than periparturient hormonal
      environment. Results provide evidence that hepatic inflammatory responses
      occurring near parturition initiate or augment adipose catabolism. In this
      context, cytokines, acute-phase proteins, and serum nonesterified fatty acids are
      key players in periparturient cow metabolism. We propose a model for integrating
      gene expression, metabolite, and liver composition data to explain physiological
      events in placenta, adipose, and liver during the periparturient period.

PMID- 16091419
TI  - The PROTEKT global study (year 4) demonstrates a continued lack of resistance
      development to telithromycin in Streptococcus pneumoniae.

PMID- 16091420
TI  - Extra-mitochondrial localisation of frataxin and its association with IscU1
      during enterocyte-like differentiation of the human colon adenocarcinoma cell
      line Caco-2.
AB  - Friedreich's ataxia is a recessive neurodegenerative disease due to insufficient
      expression of the mitochondrial protein frataxin. Although it has been shown that
      frataxin is involved in the control of intracellular iron metabolism, by
      interfering with the mitochondrial biosynthesis of proteins with iron/sulphur
      (Fe/S) clusters its role has not been well established. We studied frataxin
      protein and mRNA expression and localisation during cellular differentiation. We
      used the human colon adenocarcinoma cell line Caco-2, as it is considered a good
      model for intestinal epithelial differentiation and the study of intestinal iron
      metabolism. Here we report that the protein, but not the mRNA frataxin levels,
      increase during the enterocyte-like differentiation of Caco-2 cells, as well as
      in in-vivo-differentiated enterocytes at the upper half of the crypt-villus axis.
      Furthermore, subcellular fractionation and double immunostaining, followed by
      confocal analysis, reveal that frataxin localisation changes during Caco-2 cell
      differentiation. In particular, we found an extramitochondrial localisation of
      frataxin in differentiated cells. Finally, we demonstrate a physical interaction
      between extramitochondrial frataxin and IscU1, a cytoplasmic isoform of the human
      Fe/S cluster assembly machinery. Based on our data, we postulate that frataxin
      could be involved in the biosynthesis of iron-sulphur proteins not only within
      the mitochondria, but also in the extramitochondrial compartment. These findings
      might be of relevance for the understanding of both the pathogenesis of
      Friedreich's ataxia and the basic mechanism of Fe/S cluster biosynthesis.

PMID- 16091421
TI  - ER stress and SREBP-1 activation are implicated in beta-cell glucolipotoxicity.
AB  - The reduction in insulin secretory capacity and beta-cell mass observed in type 2
      diabetes is thought to be caused by glucolipotoxicity secondary to hyperglycemia
      and hyperlipidemia. Our aim in this study was to elucidate the underlying
      molecular mechanisms. We found a strong correlation between chronic high-glucose
      treatment and SREBP-1c activation in INS-1 cells and rat islets. Both high
      glucose treatment and SREBP-1c activation in INS-1 cells resulted in lipid
      accumulation, impaired glucose-stimulated insulin secretion, apoptosis, and
      strikingly similar gene expression patterns, including upregulation of lipogenic
      and pro-apoptotic genes and downregulation of IRS2, Bclxl and Pdx1. These
      lipotoxic effects of high glucose were largely prevented by induction of a
      dominant-negative mutant of SREBP-1c, suggesting SREBP-1c is a major factor
      responsible for beta cell glucolipotoxicity. Moreover, overexpression of another
      lipogenic transcription factor, ChREBP, in INS-1 cells did not cause
      lipotoxicity. Intriguingly, chronic high glucose treatment in INS-1 cells led to
      pronounced induction of the ER stress marker genes, BIP and Chop10. Treatment of
      rat islets with both chronic high glucose and two ER stress inducers,
      thapsigargin and tunicamycin, enhanced SREBP-1 binding to the human IRS2
      promoter. These results suggest that SREBP-1 activation caused by ER stress is
      implicated in beta-cell glucolipotoxicity.

PMID- 16091422
TI  - Neurogenic potential of human mesenchymal stem cells revisited: analysis by
      immunostaining, time-lapse video and microarray.
AB  - The possibility of generating neural cells from human bone-marrow-derived
      mesenchymal stem cells (hMSCs) by simple in vitro treatments is appealing both
      conceptually and practically. However, whether phenotypic modulations observed
      after chemical manipulation of such stem cells truly represent a genuine trans
      lineage differentiation remains to be established. We have re-evaluated the
      effects of a frequently reported biochemical approach, based on treatment with
      butylated hydroxyanisole and dimethylsulphoxide, to bring about such phenotypic
      conversion by monitoring the morphological changes induced by the treatment in
      real time, by analysing the expression of phenotype-specific protein markers and
      by assessing the modulation of transcriptome. Video time-lapse microscopy showed
      that conversion of mesenchymal stem cells to a neuron-like morphology could be
      reproduced in normal primary fibroblasts as well as mimicked by addition of drugs
      eliciting cytoskeletal collapse and disruption of focal adhesion contacts.
      Analysis of markers revealed that mesenchymal stem cells constitutively expressed
      multi-lineage traits, including several pertaining to the neural one. However,
      the applied ;neural induction' protocol neither significantly modulated the
      expression of such markers, nor induced de novo translation of other neural
      specific proteins. Similarly, global expression profiling of over 21,000 genes
      demonstrated that gene transcription was poorly affected. Most strikingly, we
      found that the set of genes whose expression was altered by the inductive
      treatment did not match those sets of genes differentially expressed when
      comparing untreated mesenchymal stem cells and immature neural tissues.
      Conversely, by comparing these gene expression profiles with that obtained from
      comparisons between the same cells and an unrelated non-neural organ, such as
      liver, we found that the adopted neural induction protocol was no more effective
      in redirecting human mesenchymal stem cells toward a neural phenotype than toward
      an endodermal hepatic pathway.

PMID- 16091423
TI  - Different intracellular trafficking of FGF1 endocytosed by the four homologous
      FGF receptors.
AB  - Many growth factors and cytokines bind to more than one receptor, but in many
      cases the different roles of the separate receptors in signal transduction are
      unclear. Intracellular sorting of ligand-receptor complexes may modulate the
      signalling, and we have here studied the intracellular trafficking of ligand
      bound to receptors for fibroblast growth factors (FGFs). For this purpose, we
      transfected HeLa cells with any one of the four tyrosine kinase FGF receptors
      (FGFR1-4). In cells expressing any one of these receptors, externally added FGF1
      was localized to sorting/early endosomes after 15 minutes at 37 degrees C. After
      longer incubation times, FGF1 internalized in cells expressing FGFR1 was
      localized mainly to late endosomes/lysosomes, similarly to EGF. By contrast, FGF1
      internalized in cells expressing FGFR4 followed largely the same intracellular
      pathway as the recycling ligand, transferrin. In cells expressing FGFR2 or FGFR3,
      sorting of FGF1 to lysosomes was somewhat less efficient than that observed for
      FGFR1. Furthermore, FGF1 was more slowly degraded in cells expressing FGFR4 than
      in cells expressing FGFR1-3 and in addition, internalized FGFR4 as such was more
      slowly degraded than the other receptors. The data indicate that after
      endocytosis, FGFR4 and its bound ligand are sorted mainly to the recycling
      compartment, whereas FGFR1-3 with ligand are sorted mainly to degradation in the
      lysosomes. Alignment of the amino acid sequence of the intracellular part of the
      four FGFRs revealed several lysines conserved in FGFR1-3 but absent in FGFR4.
      Lysines are potential ubiquitylation sites and could thus target a receptor to
      lysosomes for degradation. Indeed, we found that FGFR4 is less ubiquitylated than
      FGFR1, which could be the reason for the different sorting of the receptors.

PMID- 16091424
TI  - Modulating the strength of cadherin adhesion: evidence for a novel adhesion
      complex.
AB  - Adherens junctions and desmosomes are critical for embryogenesis and the
      integrity of adult tissues. To form these junctions, classical cadherins interact
      via alpha- and beta-catenin with the actin cytoskeleton, whereas desmosomal
      cadherins interact with the intermediate filament system. Here, we used a hormone
      activated mutant N-cadherin expressed in fibroblasts to show the existence of a
      novel classical cadherin adhesion system. N-cadherin was fused at its C-terminus
      to a modified estrogen receptor ligand-binding domain (NcadER) that binds 4
      hydroxytamoxifen (4OHT) and expressed in L cells, which lack an endogenous
      cadherin. Cells with the mutant cadherin (LNER cells) aggregated in the absence
      of 4OHT, but only in its presence formed tightly compacted aggregates like those
      formed by L cells expressing wild-type N-cadherin (LN cells). Compaction of LNER
      cells treated with 4OHT was accompanied by elevated levels of p120ctn in NcadER
      immunoprecipitates, compared to immunoprecipitates of non-treated cells, but
      without changes in alpha- and beta-catenin, or actin. Compaction induced by 4OHT
      was also accompanied by increased interaction of the NcadER with the cytoskeleton
      and increased vimentin organization. Vimentin co-immunoprecipitated with the
      NcadER/catenin complex, suggesting an interaction between cadherin and vimentin.
      The mechanism by which vimentin interacts with the cadherin appears to involve
      p120ctn as it co-immunoprecipitates and colocalizes with vimentin in the parent L
      cells, which lack a cadherin and alpha- and beta-catenins. Disrupting the actin
      cytoskeleton with cytochalasin B inhibited aggregation, whereas knocking down
      vimentin with specific siRNAs inhibited compaction. Based on our results we
      propose that a vimentin-based classical cadherin complex functions together with
      the actin-based complex to promote strong cell-cell adhesion in fibroblasts.

PMID- 16091425
TI  - Calmodulin-dependent protein kinase II, and not protein kinase C, is sufficient
      for triggering cell-cycle resumption in mammalian eggs.
AB  - Mouse eggs arrest at metaphase II following ovulation and are only triggered to
      complete meiosis when fertilized. Sperm break the cell-cycle arrest by a long
      lasting series of Ca2+ spikes that lead to an activation of the anaphase
      promoting complex/cyclosome. The signal transduction pathway is not fully
      resolved but both protein kinase C (PKC) and calmodulin-dependent protein kinase
      II (CamKII) activities increase at fertilization and previous pharmacological
      studies have implicated both in cell-cycle resumption. We have used a combination
      of pharmacological inhibitors and constitutively active cRNA constructs of
      PKCalpha and CamKIIalpha microinjected into mouse eggs to show that it is CamKII
      and not PKC that is the sufficient trigger for cell-cycle resumption from
      metaphase II arrest. Constitutively active PKC constructs had no effect on the
      resumption of meiosis but caused an immediate and persistent elevation in
      intracellular Ca2+ when store-operated Ca2+ entry was stimulated. With respect to
      resumption of meiosis, the effects of constitutively active CamKII on eggs were
      the same as sperm. Eggs underwent second polar body extrusion and pronucleus
      formation with normal timings; while both securin and cyclin B1 destruction,
      visualised by coupling to fluorescent protein tags, were complete by the time of
      polar body extrusion. Induction of a spindle checkpoint by overexpression of Mad2
      or by spindle poisons blocked CamKII-induced resumption of meiosis, but the Ca2+
      chelator BAPTA did not. Furthermore direct measurement of Ca2+ levels showed that
      CamKII did not induce exit from metaphase II arrest by raising Ca2+. Therefore,
      we conclude that PKCs may play an important role in maintaining Ca2+ spiking at
      fertilization by promoting store-operated Ca2+ entry, while CamKII transduces
      cell-cycle resumption, and lies downstream of sperm-induced Ca2+ release but
      upstream of a spindle checkpoint. These data, combined with the knowledge that
      CamKII activity increase at fertilization, suggest that mouse eggs undergo cell
      cycle resumption through stimulation of CamKII.

PMID- 16091426
TI  - PCTAIRE protein kinases interact directly with the COPII complex and modulate
      secretory cargo transport.
AB  - The export of secretory cargo from the endoplasmic reticulum is mediated by the
      COPII complex. In common with other aspects of intracellular transport, this step
      is regulated by protein kinase signalling. Recruitment of the COPII complex to
      the membrane is known to require ATP and to be blocked by the protein kinase
      inhibitor H-89. The identity of the specific protein kinase or kinases involved
      remains equivocal. Here we show that the Sec23p subunit of COPII interacts with
      PCTAIRE protein kinases. This interaction is shown using two-hybrid screening,
      direct binding and immunoprecipitation. Inhibition of PCTAIRE kinase activity by
      expression of a kinase-dead mutant, or specific depletion of PCTAIRE using RNAi,
      leads to defects in early secretory pathway function including cargo transport,
      as well as vesicular-tubular transport carrier (VTC) and Golgi localization.
      These data show a role for PCTAIRE protein kinase function in membrane traffic
      through the early secretory pathway.

PMID- 16091427
TI  - Non-enrolment of ovarian cancer patients in clinical trials: reasons and
      background.
AB  - BACKGROUND: Some retrospective analyses have suggested that participation in
      clinical trials is associated with better outcome. However, it is not clear to
      what extent selection bias contributes to this observation. PATIENTS AND METHODS:
      We evaluated the reasons for non-enrolment of ovarian cancer patients in clinical
      trials. All patients with ovarian cancer not enrolled in clinical studies and
      treated in 2001 in the participating centres were documented retrospectively and
      compared with patients enrolled in clinical trials at the same institutions
      during the same time period. RESULTS: Two hundred and seventy-four patients with
      advanced ovarian cancer (FIGO stage IIB-IV) were included, of whom 139 (51%) and
      135 (49%) patients were enrolled in this study and in prospective clinical
      trials, respectively. Ninety-four of 274 patients (34%) did not meet the
      inclusion criteria for clinical trials. Of 180 eligible patients, 28 (16%)
      refused participation and a further 17 patients (9%) were not recruited although
      they met the inclusion criteria. The non-study patients were older (66.7 versus
      57.2 years; P <0.0001), underwent less radical surgery (hysterectomy,
      oophorectomy and omentectomy performed: 61.2% versus 80.7%; P = 0.001; rate of
      lymphadenectomy 30.9% versus 45.2%; P = 0.015) and more frequently had bulky
      residual disease (residual disease >2 cm: 36.2% versus 20%; P = 0.016). However,
      62% of the non-study patients were treated with the same chemotherapy as in the
      standard arm of the respective clinical studies. CONCLUSIONS: Study patients
      differ substantially from non-study patients, thus hampering generalisation of
      study results. Our results suggest that at least some inclusion criteria for
      clinical trials should be modified to increase study participation without
      compromising safety.

PMID- 16091428
TI  - Does an apple a day keep the oncologist away?
AB  - BACKGROUND: Apples have commonly been described as a healthy food. To understand
      better their role on risk of cancer at several sites, we analyzed data from
      multicenter case-control studies conducted between 1991 and 2002 in Italy.
      PATIENTS AND METHODS: The studies included 598 patients with incident cancers of
      the oral cavity and pharynx, 304 of the oesophagus, 460 of the larynx, 1953 of
      the colorectum, 2569 of the breast, 1031 of the ovary and 1294 of the prostate.
      The comparison group included a total of 6629 patients admitted to the same
      network of hospitals as cases for acute, non-neoplastic diseases. Multivariate
      odds ratios (OR) were obtained with allowance for age, sex, study center,
      education, body mass index, tobacco smoking, alcohol drinking, total energy
      intake, vegetable consumption and physical activity. RESULTS: Compared with
      subjects reporting consumption of <1 apple/day, the ORs for > or =1 apple/day
      were 0.79 [95% confidence interval (CI) 0.62-1.00] for cancers of the oral cavity
      and pharynx, 0.75 (95% CI 0.54-1.03) for oesophagus, 0.80 (95% CI 0.71-0.90) for
      colorectum, 0.58 (95% CI 0.44-0.76) for larynx, 0.82 (95% CI 0.73-0.92) for
      breast, 0.85 (95% CI 0.72-1.00) for ovary and 0.91 (95% CI 0.77-1.07) for
      prostate. CONCLUSION: This investigation found a consistent inverse association
      between apples and risk of various cancers.

PMID- 16091429
TI  - Neoadjuvant chemotherapy with infusional 5-fluorouracil, adriamycin and
      cyclophosphamide (iFAC) in locally advanced breast cancer: an early response
      predicts good prognosis.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy and safety of
      neoadjuvant chemotherapy with infusional 5-fluorouracil (5-FU), adriamycin and
      cyclophosphamide (iFAC) in locally advanced breast cancer (LABC). PATIENTS AND
      METHODS: Eighty-two LABC patients were treated with neoadjuvant iFAC chemotherapy
      including infusional 5-FU (1000 mg/m2, continuous intravenous infusion, days 1
      3), adriamycin (40 mg/m2, intravenous bolus, day 1) and cyclophosphamide (600
      mg/m2, intravenous bolus, day 1) every 3 weeks until maximum tumor response.
      Patients subsequently received surgery, adjuvant chemotherapy, radiotherapy and
      hormonal therapy as appropriate. RESULTS: Downstaging occurred in 71 of the 82
      patients (86.6%). Seventy-two patients (67 patients with downstaging and five
      patients without downstaging) were resectable (resectability rate, 87.8%). The
      clinical response rate was 84.2%, with a complete response (CR) rate of 17.1% and
      a pathological CR rate of 7.8%. During 891 cycles of chemotherapy, the most
      common grade 3/4 hematological toxicity was leukopenia (36.0%). There were no
      treatment-related deaths. The median follow-up period was 51 months, with a
      median overall survival (OS) of 66 months, and a 5 year OS rate of 50.9% for all
      patients. The 5 year OS and disease-free survival (DFS) rates of the 64 patients
      who underwent surgery were 55.8% and 44.7%, respectively. CONCLUSIONS:
      Neoadjuvant chemotherapy with iFAC had a comparable response rate and DFS to the
      conventional bolus FAC regimen, with an acceptable toxicity in LABC using the
      AJCC 2002 staging system. An early response to neoadjuvant iFAC was a favorable
      prognostic factor.

PMID- 16091430
TI  - Role of swarming in the formation of crystalline Proteus mirabilis biofilms on
      urinary catheters.
AB  - The care of many patients undergoing long-term bladder catheterization is
      frequently complicated by infection with Proteus mirabilis. These organisms
      colonize the catheter, forming surface biofilm communities, and their urease
      activity generates alkaline conditions under which crystals of magnesium ammonium
      phosphate and calcium phosphate are formed and become trapped in the biofilm. As
      the biofilm develops it obstructs the flow of urine through the catheter, causing
      either incontinence due to leakage of urine around the catheter or retention of
      urine in the bladder. The aim of this study was to investigate the role of the
      surface-associated swarming motility of P. mirabilis in the initiation and
      development of these crystalline catheter biofilms. A set of stable transposon
      mutants with a range of swimming and swarming abilities were tested for their
      ability to colonize silicone surfaces in a parallel-plate flow cell. A laboratory
      model of the catheterized bladder was then used to examine their ability to form
      crystalline, catheter-blocking biofilms. The results showed that neither swarming
      nor swimming motility was required for the attachment of P. mirabilis to
      silicone. Mutants deficient in swarming and swimming were also capable of forming
      crystalline biofilms and blocking catheters more rapidly than the wild-type
      strain.

PMID- 16091432
TI  - Identification of staphylococci by 16S internal transcribed spacer rRNA gene
      restriction fragment length polymorphism.
AB  - The capacity of 16S internal transcribed spacer (16S-ITS) rRNA gene RFLP to
      differentiate 16 type strains and nine clinical isolates of staphylococci was
      evaluated. The 16S rRNA gene was amplified together with the ITS region and the
      amplification products were digested with TaqI restriction enzyme. Analysis of
      the 16S-ITS rRNA gene RFLP profiles differentiated each of the 16 type strains
      into distinct RFLP haplotypes.

PMID- 16091433
TI  - Evaluation of commercial kits for the identification of Neisseria gonorrhoeae.
AB  - Eight identification methods were evaluated against 100 isolates of Neisseria
      gonorrhoeae and 21 non-gonococcal Neisseria strains. The methods examined
      included four commercial biochemical kits, API NH, RapID NH, Gonochek II and
      Neisseria Preformed Enzyme Test (PET), three immunological kits, Phadebact
      Monoclonal GC test, GonoGen II and MicroTrak, and one in-house carbohydrate
      utilization method, cystine trypticase agar (CTA) sugars. The percentage of
      isolates unambiguously identified as N. gonorrhoeae by each of the methods was as
      follows: API NH, 66 %; RapID NH, 64 %; GonoChek II, 66 %; Neisseria PET, 66 %;
      Phadebact Monoclonal GC OMNI test, 99 %; GonoGen II, 100 %; MicroTrak, 100 %; and
      CTA sugars, 96 %. The low sensitivity of the biochemical kits for the
      identification of N. gonorrhoeae was due to a lack of the enzyme proline
      iminopeptidase (Pip) in 34 % of the isolates examined. All the biochemical kits
      utilized the presence of this enzyme as a marker for N. gonorrhoeae. The
      Phadebact Monoclonal GC kit, GonoGen II, MicroTrak, CTA sugars and the API NH kit
      all exhibited high specificity, but non-gonococcal Neisseria were misidentified
      as N. gonorrhoeae using RapID NH (two strains), Gonochek II (11 strains) and
      Neisseria PET (11 strains). Whilst the isolates examined in this study may not be
      truly representative, they do indicate that N. gonorrhoeae isolates lacking the
      enzyme Pip can give anomalous results when using commercially available
      biochemical tests and that some non-pathogenic Neisseria species are still being
      misidentified using some biochemical kits. This further reinforces the
      recommendation that any dubious biochemical result should be confirmed with an
      immunological test.

PMID- 16091431
TI  - Cellular immune response induced by Salmonella enterica serotype Typhi iron
      regulated outer-membrane proteins at peripheral and mucosal levels.
AB  - The role of purified iron-regulated outer-membrane proteins (IROMPs) from
      Salmonella enterica serotype Typhi in modulation of specific T-cell responses was
      studied. The cellular immune response induced by IROMPs was measured by assessing
      the delayed-type hypersensitivity (DTH) response, lymphocyte proliferation, T
      cell phenotyping and cytokine-producing cells using lymphocytes isolated from the
      spleen and Peyer's patches of IROMPs-immunized, immunized-challenged, infected
      and control mice. IROMPs immunization resulted in an enhanced DTH response and
      exhibited a significant increase in the protein-specific proliferative response
      of lymphocyte from the spleen as well as Peyer's patches. A significant increase
      was also observed in the ratio of CD4+/CD8+ cells in the immunized mice as
      compared to the infected mice. Results of the cytokine analysis revealed that
      during the initial period there was increased production of interleukin (IL)-2-
      and interferon (IFN)-gamma-producing cells in the spleen and Peyer's patches,
      indicating a Th1 type response, whereas in the later period of the study,
      increased production of IL-4-producing cells suggested a Th2 type response. The
      results of this study suggest a role for S. Typhi IROMPs in modulating the
      cellular immune response at peripheral and mucosal levels.

PMID- 16091434
TI  - Characterization of a tandem repeat polymorphism in Rickettsia strains.
AB  - Mediterranean spotted fever (MSF) is a tick-borne rickettsiosis caused by
      'Rickettsia conorii complex' strains. In Portugal, R. conorii and Israeli tick
      typhus (ITT) are the aetiological agents of this disease. A novel 65 bp tandem
      repeat was identified by the analysis of the R. conorii Malish 7 whole genome
      sequence with an appropriate algorithm for searching for repeated sequences. The
      variable number tandem repeat (VNTR) was named VNTR Rc-65 and this locus was
      amplified by PCR and sequenced in order to characterize the repeat diversity
      within different rickettsial strains including Portuguese strains isolated from
      clinical and vector samples. The VNTR Rc-65 has seven alleles within the
      rickettsial strains studied and a diversity index value of 0.71, meaning that
      this locus has a great discriminatory capacity and therefore can be used for
      identification of closely related strains. PCR amplification of the Rc-65 locus
      can be used to differentiate between the Portuguese R. conorii Malish-like and
      Israeli tick typhus strains, enabling a more accurate and rapid identification of
      these rickettsial isolates.

PMID- 16091435
TI  - Increased sensitivity of bacterial detection in cerebrospinal fluid by
      fluorescent staining on low-fluorescence membrane filters.
AB  - A membrane-filter-based, fluorescent Gram stain method for bacterial detection in
      cerebrospinal fluid samples was developed and evaluated as a rapid, sensitive
      alternative to standard Gram stain protocols. A recently developed, modified
      version of the aluminium oxide membrane Anopore with low-fluorescence optical
      properties showed superior performance in this application. Other aspects of the
      fluorescent Gram stain system that were evaluated include membrane filter
      selection, strategies to reduce fluorescence fading and the effect of patient
      blood cells on bacterial detection in the fluorescently stained cerebrospinal
      fluid samples. The combination of the membrane filter's bacteria-concentrating
      ability and absolute retention along with high-contrast, fluorescent Gram
      discriminating dyes enabled rapid bacterial detection and Gram discrimination,
      with a 1-1.5 order of magnitude increase in the bacterial concentration limit of
      detection.

PMID- 16091436
TI  - Repetitive-DNA-element PCR fingerprinting and antibiotic resistance of pan
      European multi-resistant Acinetobacter baumannii clone III strains.
AB  - In the present study, it was shown that repetitive-DNA-element PCR fingerprinting
      using the (GTG)5 primer [(GTG)5-PCR] is a rapid and reliable tool to
      genotypically differentiate members of the recently described pan-European multi
      resistant Acinetobacter baumannii (MAB) clone III from the known MAB clones I and
      II. The identification of four new representatives of the MAB clone III dating
      from 1991 to 1993 by (GTG)5-PCR indicates that this clone has persisted in
      European hospitals since the beginning of the 1990s. Tetracycline (TET)
      resistance was found to be common among clone III strains, including one strain
      that also displayed resistance to minocycline. The TET-resistance phenotype in
      this MAB clone appeared to be strongly associated with the presence of the efflux
      type gene tet(A), but the fact that some members lack this gene or have acquired
      an additional tet gene [i.e. tet(M)] suggests that the tet gene carriage in the
      pan-European clone III population may have diversified in time and space. In
      contrast, all clone III strains shared the previously described aminoglycoside
      resistotype encoded by the aminoglycoside-modifying genes aphA6 and the class 1
      integron-associated aadB, which may point to the fact that these genes probably
      are more stably inherited in MAB clone III compared to tet genes.

PMID- 16091437
TI  - Species identification of mutans streptococci by groESL gene sequence.
AB  - The near full-length sequences of the groESL genes were determined and analysed
      among eight reference strains (serotypes a to h) representing five species of
      mutans group streptococci. The groES sequences from these reference strains
      revealed that there are two lengths (285 and 288 bp) in the five species. The
      intergenic spacer between groES and groEL appears to be a unique marker for
      species, with a variable size (ranging from 111 to 310 bp) and sequence.
      Phylogenetic analysis of groES and groEL separated the eight serotypes into two
      major clusters. Strains of serotypes b, c, e and f were highly related and had
      groES gene sequences of the same length, 288 bp, while strains of serotypes a, d,
      g and h were also closely related and their groES gene sequence lengths were 285
      bp. The groESL sequences in clinical isolates of three serotypes of S. mutans
      were analysed for intraspecies polymorphism. The results showed that the groESL
      sequences could provide information for differentiation among species, but were
      unable to distinguish serotypes of the same species. Based on the determined
      sequences, a PCR assay was developed that could differentiate members of the
      mutans streptococci by amplicon size and provide an alternative way for
      distinguishing mutans streptococci from other viridans streptococci.

PMID- 16091438
TI  - Evaluation of two enzyme immunoassays for detecting Helicobacter pylori in stool
      specimens of dyspeptic patients after eradication therapy.
AB  - The aim of the current study was to assess the reliability of two enzyme
      immunoassays in detecting the Helicobacter pylori status of stool specimens of
      Turkish dyspeptic patients in the post-treatment period. Forty-eight patients
      with non-ulcer dyspepsia who were positive for H. pylori underwent a 1 week
      regimen of triple therapy. Stool samples of patients were obtained 2 and 6 weeks
      after eradication therapy and a [13C]urea breath test was performed 6 weeks after
      therapy in order to assess the reliability of mAb-based (Amplified IDEIA HpStAR,
      DakoCytomation) and polyclonal-antiserum-based (Premier Platinum HpSA, Meridian
      Diagnostics) stool antigen test kits and to compare their diagnostic accuracies.
      Using a minimum cutoff OD450 value of 0.19 for Amplified IDEIA HpStAR and 0.16
      for Premier Platinum HpSA the sensitivity, specificity, positive predictive
      value, negative predictive value and diagnostic accuracy of the tests were
      determined 2 and 6 weeks after completion of eradication therapy. At both the
      second and the sixth week in the post-treatment period the diagnostic accuracy of
      Amplified IDEIA HpStAR was significantly better than the Premier Platinum's (75%
      versus 50%, S2=6.4; P=0.011, and 90% versus 69%, S2=6.316; P=0.012,
      respectively). In light of these findings the mAb-based Amplified IDEIA HpStAR
      has a high diagnostic accuracy for H. pylori infection in Turkish dyspeptic
      patients 6 weeks after completion of eradication therapy.

PMID- 16091439
TI  - Genomic analysis of a multidrug-resistant strain of enterohaemorrhagic
      Escherichia coli O157:H7 causing a family outbreak in Japan.
AB  - A family outbreak of enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection
      occurred in October 2003 in the Hiroshima prefecture, Japan. Four isolates of
      EHEC O157:H7, 03064, 03065, 03066 and 03067, were recovered from a 1-year-old
      daughter, mother, father and 3-year-old daughter, respectively. All EHEC O157:H7
      isolates were positive for Stx1 and Stx2 Shiga toxins. Surprisingly, DNA
      fingerprinting profiles obtained by PFGE showed that the first isolate, 03064,
      had unique XbaI and BlnI profiles that differed from the other three isolates.
      Also, plasmid analysis results revealed that isolate 03064 contained an extra
      plasmid larger than the classic large plasmid of EHEC O157, pO157 (93.6 kb). This
      new plasmid was named pMDR157. Furthermore, isolate 03064 showed a multidrug
      resistance (MDR) phenotype against streptomycin, spectinomycin, co-trimoxazole
      (trimethoprim/sulfamethoxazole), ampicillin and tetracycline; the other isolates
      were completely sensitive to these antibiotics. Molecular analysis of the MDR
      phenotype in this unique strain revealed the presence of a class 1 integron
      containing two gene cassettes: a dihydrofolate reductase type 1 gene (dfrI),
      which confers resistance to trimethoprim, and an aminoglycoside adenyltransferase
      gene (aadA1), which confers resistance to streptomycin and spectinomycin.
      Southern blot hybridization showed that the class 1 integron was located in the
      extra plasmid, pMDR157. The ampicillin resistance was found to be due to the
      presence of the TEM-1-type beta-lactamase gene. The MDR phenotype was transferred
      successfully to E. coli HB101 by conjugation, indicating that both the class 1
      integron and the TEM-1 beta-lactamase were located on the conjugative
      transferable plasmid, pMDR157. To the authors' knowledge, this is the first
      report of the identification of a beta-lactamase gene in EHEC O157.

PMID- 16091440
TI  - Assessment of possible tuberculous lymphadenopathy by PCR compared to non
      molecular methods.
AB  - Tuberculosis is a major public health problem in India and other developing
      countries and has formed a lethal partnership with AIDS. It often presents a
      diagnostic challenge especially when clinical presentation is suggestive but
      bacteriological proof is lacking. The objective of this study was to compare the
      various diagnostic techniques in clinically suspected cases of tubercular lymph
      nodes and to find a suitable, cost-effective but sensitive and specific method
      for diagnosis. A total of 100 cases were recruited for the study. Fine needle
      aspiration cytology was done in all cases and the smears prepared were processed
      for Giemsa, Ziehl-Neelsen's, Kinyoun and Papanicolaou stains. Parts of the
      aspirated materials were assessed by fluorescent staining, culture and PCR.
      Seventy-four percent of aspirates were positive by fluorescent stain while only
      22% were positive by culture. PCR could be performed in 55 cases, out of which 22
      (40%) were positive. When compared to culture, the sensitivity and specificity of
      PCR were found to be 89.5% and 86.1%, respectively. Fluorescent stain was found
      to be the most sensitive (81.8%) of the conventional methods but showed poor
      specificity (28.2%). Interestingly, PCR detected 80% of smear-negative but
      culture-positive cases.

PMID- 16091441
TI  - Enterovirus RNA sequences in sera of schoolchildren in the general population and
      their association with type 1-diabetes-associated autoantibodies.
AB  - Type 1 diabetes (T1D) is an autoimmune disease linked with genetic factors as
      well as with environmental triggers, such as virus infections, but the aetiology
      is still unclear. The authors analysed serum from autoantibody-positive (n=50)
      and autoantibody-negative (n=50) schoolchildren as well as children newly
      diagnosed with T1D (n=47; time from diagnosis, median 5 days, interquartile range
      1-12 days) for the presence and frequency of enterovirus (EV) and adenovirus
      sequences. The autoantibody-positive and -negative groups were part of the
      Karlsburg Type 1 Diabetes Risk Study of a Normal Schoolchild Population, which
      represents a general population without T1D first-degree relatives. There was no
      significant seasonality of sampling in any of the three groups investigated. EV
      RNA sequences were detected in 10 of 50 (20%) autoantibody-positive children and
      in 17 of 47 (36%) children newly diagnosed with T1D, but only in two of 50 (4%)
      of the age- and sex-matched controls (P<0.05, P<0.001). Characterization of the
      EV amplicons by direct sequencing revealed high homology with coxsackievirus B
      group. For adenovirus we found no data to support an association with T1D. The
      data support the hypothesis that different enteroviruses may be aetiologically
      important as a trigger and/or accelerating factor in the process of T1D
      development.

PMID- 16091442
TI  - Nosocomial spread of multi-resistant Klebsiella pneumoniae containing a plasmid
      encoding multiple beta-lactamases.
AB  - Six Klebsiella pneumoniae isolates that exhibited resistance to a wide spectrum
      of antibiotics were recovered from the intensive care units in the First
      Affiliated Hospital, Zhejiang University, Hangzhou, China. All isolates contained
      two plasmids of approximately 95 kb and 200 kb. The 95 kb plasmid was shown to be
      transferable by conjugation experiments. Isoelectric focusing patterns of the
      beta-lactamases extracted from the six transconjugants were identical, displaying
      five pI bands: 5.4, 7.75, 8.0, 8.2 and 8.4. The band corresponding to a pI of
      7.75 could be inhibited by cloxacillin but not clavulanic acid, while the other
      bands could be inhibited by clavulanic acid but not cloxacillin. The 95 kb
      plasmid was digested with HindIII and a recombinant plasmid pT948 was obtained.
      The insert was found to contain blaDHA-1, regulatory gene ampR and an insertion
      element (IS26), which was downstream of blaDHA-1. PCR and DNA sequencing results
      confirmed that the 95 kb plasmid encoded at least four beta-lactamase genes:
      blaTEM-1, blaSHV-12), blaCTX-M-3 and blaDHA-1. Epidemiological typing by PFGE of
      the six clinical isolates of K. pneumoniae demonstrated identical genotypic
      patterns. In conclusion, all results indicated that the six multi-drug resistant
      clinical isolates of K. pneumoniae most probably originated from one clone and
      caused a localized epidemic in the intensive care units.

PMID- 16091443
TI  - Hydrogen sulfide-producing bacteria in tongue biofilm and their relationship with
      oral malodour.
AB  - The aims of this study were to identify hydrogen sulfide (H2S)-producing bacteria
      among tongue biofilm microflora and to investigate the relationship between
      bacterial flora and H2S levels in mouth air. Oral malodour levels in 10 subjects
      (age 21-56 years) were assessed by gas chromatography, and Breathtron and
      organoleptic scores. Based on these assessments, subjects were divided into two
      groups: an odour group and a no/low odour group. Tongue coatings were sampled and
      spread onto Fastidious Anaerobe Agar plates containing 0.05% cysteine, 0.12%
      glutathione and 0.02% lead acetate, and were then incubated anaerobically at 37
      degrees C for 2 weeks. Bacteria forming black or grey colonies were selected as
      H2S-producing phenotypes. The numbers of total bacteria (P<0.005) and H2S
      producing bacteria (P<0.05) in the odour group were significantly larger than
      those in the no/low odour group. Bacteria forming black or grey colonies (126
      isolates from the odour group; 242 isolates from the no/low odour group) were
      subcultured, confirmed as producing H2S and identified according to 16S rRNA gene
      sequencing. Species of Veillonella (38.1% in odour group; 46.3% in no/low odour
      group), Actinomyces (25.4%; 17.7%) and Prevotella (10.3%; 7.8%) were the
      predominant H2S-producing bacteria in both the odour and no/low odour groups.
      These results suggest that an increase in the number of H2S-producing bacteria in
      the tongue biofilm is responsible for oral malodour, although the bacterial
      composition of tongue biofilm was similar between the two groups.

PMID- 16091444
TI  - Direct sequencing of Scedosporium apiospermum DNA in the diagnosis of a case of
      keratitis.
AB  - The present report describes the diagnostic strategy followed in a case of
      keratomycosis. Together with conventional methods, a molecular strategy that
      involved the direct sequencing of an amplified portion of the genome encompassing
      the internal transcribed spacer 1 and 2 regions and sequence analysis was used.
      The data highlight the diagnostic role of molecular techniques, in parallel with
      conventional methods, in the management of ocular infections of fungal aetiology.

PMID- 16091445
TI  - Community-acquired vancomycin-resistant Enterococcus faecium: a case report from
      Malaysia.
AB  - Vancomycin-resistant enterococci (VRE) are formidable organisms renowned for
      their ability to cause infections with limited treatment options and their
      potential for transferring resistance genes to other Gram-positive bacteria.
      Usually associated with nosocomial infections, VRE are rarely reported as a cause
      of community-acquired infection. Presented here is a case of community-acquired
      infection due to vancomycin-resistant Enterococcus faecium. The patient had been
      applying herbal leaves topically to his cheek to treat a buccal space abscess,
      resulting in a burn of the overlying skin. From pus aspirated via the skin a pure
      culture of E. faecium was grown that was resistant to vancomycin with a MIC of
      >256 microg ml-1 by the E test and resistant to teicoplanin by disc diffusion,
      consistent with the VanA phenotype. The organism was suspected of contaminating
      the leaf and infecting the patient via the burnt skin. This case highlights the
      need for further studies on the community prevalence of VRE among humans and
      animals to define unrecognized silent reservoirs for VRE, which may pose a threat
      to public health.

PMID- 16091446
TI  - Probiotics for recurrent Clostridium difficile disease.

PMID- 16091447
TI  - Use of ciprofloxacin for treating leptospirosis--need for clinical trials.

PMID- 16091448
TI  - Evidence for ineffective erythropoiesis in severe sickle cell disease.
AB  - Peripheral destruction of sickled erythrocytes is a cardinal feature of sickle
      cell disease (SCD). Less well established is the potential contribution of
      ineffective erythropoiesis to the pathophysiology of this hemoglobinopathy. Since
      patients with SCD frequently develop mixed hematopoietic chimerism after
      allogeneic nonmyeloablative stem cell transplantation, we used this opportunity
      to directly compare the differentiation and survival of SCD and donor-derived
      erythropoiesis in vivo. Donor and recipient erythropoiesis was compared in 4
      patients with SCD and 4 without SCD who developed stable mixed hematopoietic
      chimerism following transplant. Molecular analysis of chimerism in peripheral
      blood and bone marrow demonstrated higher expression of donor-derived beta-globin
      RNA relative to the level of donor-derived genomic DNA in patients with SCD.
      Analysis of chimerism in immature (glycophorin A-positive [GYPA(+)], CD71(hi))
      and mature (GYPA(+), CD71(neg)) erythroblasts confirmed the intramedullary loss
      of SS erythroblasts with progressive maturation. In patients with SCD, relative
      enrichment of donor erythroid precursors began to appear at the onset of
      hemoglobinization. Ineffective erythropoiesis of homozygous hemoglobin S (SS)
      progenitors thus provides a maturation advantage for homozygous hemoglobin A (AA)
      or heterozygous hemoglobin S/hemoglobin A (SA) donor erythroid precursor cells
      that results in greater donor contribution to overall erythropoiesis following
      stem-cell transplantation and improvement of clinical disease.

PMID- 16091449
TI  - Analysis of T-cell repertoire diversity in Wiskott-Aldrich syndrome.
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by
      thrombocytopenia, eczema, and variable degrees of impaired cellular and humoral
      immunity. Age-dependent T-cell lymphopenia has been described in WAS, however,
      the diversity of the T-cell compartment over time in these patients has not been
      characterized. We have used complementarity-determining region 3 (CDR3) size
      distribution analysis to assess T-cell receptor (TCR) Vbeta repertoire in 13
      patients with WAS. Diverse CDR3 size pattern was demonstrated in patients under
      15 years of age regardless of the levels of WAS protein (WASP) expression. In
      contrast, older patients showed significantly higher skewing of TCRVbeta
      repertoire as compared with healthy adults. We did not find correlation between
      clinical score and complexity of TCRVbeta repertoire. These findings suggest that
      WASP deficiency does not limit thymic generation of a normal TCR and indicate
      that T-cell oligoclonality may contribute to the immunodeficiency in older
      patients with WAS.

PMID- 16091450
TI  - The alphaC domains of fibrinogen affect the structure of the fibrin clot, its
      physical properties, and its susceptibility to fibrinolysis.
AB  - The functions of the alphaC domains of fibrinogen in clotting and fibrinolysis,
      which have long been enigmatic, were determined using recombinant fibrinogen
      truncated at Aalpha chain residue 251. Scanning electron microscopy and confocal
      microscopy revealed that the fibers of alpha251 clots were thinner and denser,
      with more branch points than fibers of control clots. Consistent with these
      results, the permeability of alpha251 clots was nearly half that of control
      clots. Together, these results suggest that in normal clot formation, the alphaC
      domains enhance lateral aggregation to produce thicker fibers. The viscoelastic
      properties of alpha251 fibrin clots differed markedly from control clots;
      alpha251 clots were much less stiff and showed more plastic deformation,
      indicating that interactions between the alphaC domains in normal clots play a
      major role in determining the clot's mechanical properties. Comparing factor
      XIIIa cross-linked alpha251 and control clots showed that gamma chain cross
      linking had a significant effect on clot stiffness. Plasmin-catalyzed lysis of
      alpha251 clots, monitored with both macroscopic and microscopic methods, was
      faster than lysis of control clots. In conclusion, these studies provide the
      first definitive evidence that the alphaC domains play an important role in
      determining the structure and biophysical properties of clots and their
      susceptibility to fibrinolysis.

PMID- 16091451
TI  - Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and
      repopulating ability of hematopoietic stem cells.
AB  - The homeobox gene Hoxa-9 is normally expressed in primitive bone marrow cells,
      and overexpression of Hoxa-9 markedly expands hematopoietic stem cells,
      suggesting a function in early hematopoiesis. We present evidence for major
      functional defects in Hoxa-9-/- hematopoietic stem cells. Hoxa-9-/- marrow cells
      have normal numbers of immunophenotypic stem cells (Lin(-)c-kit(+)flk-2(-)Sca-1+
      [KLFS] cells). However, sublethally irradiated Hoxa-9-/- mice develop persistent
      pancytopenia, indicating unusual sensitivity to ionizing irradiation. In
      competitive transplantation assays, Hoxa-9-/- cells showed an 8-fold reduction in
      multilineage long-term repopulating ability, a defect not seen in marrow cells
      deficient for the adjacent Hoxa-10 gene. Single-cell cultures of KLFS cells
      showed a 4-fold reduction in large high-proliferation potential colonies. In
      liquid cultures, Hoxa-9-deficient Lin(-)Sca-1(+) cells showed slowed
      proliferation (a 5-fold reduction in cell numbers at day 8) and delayed emergence
      of committed progenitors (a 5-fold decrease in colony-forming cells). Slowing of
      proliferation was accompanied by a delay in myeloid maturation, with a decrease
      in Gr-1hiMac-1hi cells at the end of the culture. Retroviral transduction with a
      Hoxa-9 expression vector dramatically enhanced the cytokine-driven proliferation
      and in vivo engraftment of Hoxa-9-/- marrow cells. Hoxa-9 appears to be
      specifically required for normal hematopoietic stem cell function both in vitro
      and in vivo.

PMID- 16091452
TI  - Phenotypic and functional analyses of dendritic cells in patients with
      lymphoproliferative disease of granular lymphocytes (LDGL).
AB  - We investigated whether dendritic cells (DCs) play a role in favoring granular
      lymphocyte (GL) proliferation in patients with lymphoproliferative disease of
      granular lymphocytes (LDGL). The presence of in vivo circulating DCs was studied
      in 11 patients (5 CD3+ and 6 CD3- LDGL). Autologous immature (iDCs) and mature
      (mDCs) DCs generated in vitro were studied for stimulatory activity on cell
      proliferation of CD3+ and CD3- GLs. The topographic organization of GLs and DCs
      was also studied in bone marrow (BM) biopsies. Peripheral blood (PB) CD3- GLs
      from patients showed significant proliferative activity in the presence of iDCs
      and mDCs. Conversely, monoclonal CD3+ GLs were unresponsive to autologous and
      allogeneic PB DCs. Analysis of BM biopsies demonstrated a topographic
      distribution of DCs and GLs that indicates contact between the 2 cell types. On
      functional assays, DCs obtained from BM were more efficient than PB DCs in
      stimulating CD3- GLs, and surprisingly, a low but definite stimulatory effect was
      demonstrated also on CD3+ GLs. The putative contact between DCs and GLs in the BM
      and, more crucial, the proliferative response of discrete GL populations to DC
      stimulation suggest the presence of a specific antigen within BM DCs, providing
      evidence for a role of DCs in the pathogenesis of LDGL.

PMID- 16091453
TI  - Intrabodies targeting the Kaposi sarcoma-associated herpesvirus latency antigen
      inhibit viral persistence in lymphoma cells.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen-1
      (LANA1) is essential for the maintenance and segregation of viral episomes in
      KSHV latently infected B cells. We report development of intracellular, rabbit
      derived antibodies generated by phage display technology, which bind to N
      terminal LANA1 epitopes and neutralize the chromosome-binding activity of LANA1.
      Although these cloned single-chain variable fragments (scFvs) show relatively low
      binding affinities for the LANA1 viral antigen in in vitro assays, they
      nonetheless outcompete KSHV-seropositive human sera for LANA1 epitope binding. In
      heterologous cells, intracellular intrabody expression inhibits LANA1-dependent
      plasmid maintenance of both an artificial plasmid containing KSHV LANA1 binding
      sequences and a bacterial artificial chromosome containing the entire KSHV
      genome. In KSHV naturally infected primary effusion lymphoma cells, intracellular
      intrabody expression causes a reduction or loss of the typical LANA1 punctate,
      nuclear pattern. This morphologically apparent LANA1 dispersion correlates to
      loss of viral episome by molecular analysis. These data suggest a novel approach
      to antiherpes viral therapy and confirm LANA1 is critical target for
      neutralization of KSHV viral latency.

PMID- 16091454
TI  - Cell of origin, germinal center versus nongerminal center, determined by
      immunohistochemistry on tissue microarray, does not correlate with outcome in
      patients with relapsed and refractory DLBCL.
AB  - A number of prognostic factors affect outcome in patients with relapsed or
      primary refractory diffuse large B-cell lymphoma (DLBCL), including refractory
      disease and the second-line age-adjusted international prognostic index. In de
      novo DLBCL, the cell of orgin, as determined by expression microarray analysis or
      immunohistochemistry (IHC), predicts event-free survival (EFS). We evaluated the
      cell of origin, as well as other pathologic markers of outcome, on the repeat
      biopsy specimen of 88 transplantation-eligible patients undergoing ifosfamide,
      carboplatin, etoposide (ICE) second-line chemotherapy (SLT) followed by high-dose
      therapy (HDT) and autologous stem cell transplantation (ASCT) to see if were they
      prognostic in the salvage setting. Pretreatment clinical factors were well
      balanced between the cohorts. There was no significant difference in response to
      SLT, HDT, event-free or overall survival based on the cell of origin or any of
      the common pathologic markers examined. The cell of origin as determined by IHC
      does not predict outcome in transplantation-eligible patients with relapsed or
      primary refractory DLBCL.

PMID- 16091455
TI  - Functional consequences of the human DMT1 (SLC11A2) mutation on protein
      expression and iron uptake.
AB  - We have previously described a case of severe hypochromic microcytic anemia
      caused by a homozygous mutation in the divalent metal transporter 1 (DMT1 1285G >
      C). This mutation encodes for an amino acid substitution (E399D) and causes
      preferential skipping of exon 12 during processing of the DMT1 mRNA. To examine
      the functional consequences of this mutation, full-length DMT1 transcript with
      the patient's point mutation or a DMT1 transcript with exon 12 deleted was
      expressed in Chinese hamster ovary (CHO) cells. Our results demonstrate that the
      E399D substitution has no effect on protein expression and function. In contrast,
      deletion of exon 12 led to a decreased expression of the protein and disruption
      of its subcellular localization and iron uptake activity. We hypothesize that the
      residual protein in hematopoietic cells represents the functional E399D DMT1
      variant, but because of its quantitative reduction, the iron uptake activity of
      DMT1 in the patient's erythroid cells is severely suppressed.

PMID- 16091456
TI  - High-dose factor VIII inhibits factor VIII-specific memory B cells in hemophilia
      A with factor VIII inhibitors.
AB  - Hemophilia A in its severe form is a life-threatening hemorrhagic disease that is
      caused by mutations in the factor VIII (FVIII) gene (symbol F8). About 25% of
      patients who receive replacement therapy develop neutralizing antibodies that
      inhibit the function of substituted FVIII. Long-term application of high doses of
      FVIII has evolved as an effective therapy to eradicate the antibodies and to
      induce long-lasting immune tolerance. Little is known, however, about the
      immunologic mechanisms that cause the down-modulation of anti-FVIII antibodies by
      high doses of FVIII. We report that high doses of FVIII inhibit the restimulation
      of FVIII-specific memory B cells and their differentiation into antibody
      secreting plasma cells in vitro and in vivo in a murine model of hemophilia A.
      The inhibition of memory B-cell responses is irreversible and not mediated by
      FVIII-specific T cells. Furthermore, it seems to involve the activation of
      caspases. We conclude that the inhibition of FVIII-specific memory B cells might
      be an early event in the down-modulation of anti-FVIII antibodies in patients
      with hemophilia A who receive high doses of FVIII.

PMID- 16091459
TI  - Observation of the skin-depth effect on the Casimir force between metallic
      surfaces.
AB  - We have performed measurements of the Casimir force between a metallic plate and
      a transparent sphere coated with metallic films of different thicknesses. We have
      observed that, if the thickness of the coating is less than the skin-depth of the
      electromagnetic modes that mostly contribute to the interaction, the force is
      significantly smaller than that measured with a thick bulk-like film. Our results
      provide direct evidence of the skin-depth effect on the Casimir force between
      metallic surfaces.

PMID- 16091458
TI  - Mechanical control of tissue growth: function follows form.

PMID- 16091457
TI  - Transcription factor GATA-1 potently represses the expression of the HIV-1
      coreceptor CCR5 in human T cells and dendritic cells.
AB  - CC chemokine receptor 5 (CCR5) is the major HIV-1 coreceptor and its expression
      levels are a critical determinant of HIV-1 infection. However, the molecular
      mechanisms of CCR5 regulation in primary targets of HIV-1 remain unknown. Despite
      binding to conserved DNA elements, we show that the transcription factors GATA
      binding protein 1 (GATA-1) and GATA-3 differentially suppress the expression of
      CCR5 in stem-cell-derived dendritic cells and primary human T-cell subsets. In
      addition, GATA-1 expression was also more potent than GATA-3 in suppressing T
      helper 1 (Th1)-associated genes, interferon-gamma (IFNgamma), and CXC chemokine
      receptor-3 (CXCR3). GATA-1, but not GATA-3, potently suppressed CCR5
      transcription, thereby rendering human T cells resistant to CCR5-tropic HIV-1
      infection. However, GATA-1 could also serve as a surrogate for GATA-3 in its
      canonic role of programming Th2 gene expression. These findings provide insight
      into GATA-3-mediated gene regulation during T-cell differentiation. Importantly,
      decoding the mechanisms of GATA-1-mediated repression of CCR5 may offer an
      opportunity to develop novel approaches to inhibit CCR5 expression in T cells.

PMID- 16091460
TI  - Structure of trigger factor binding domain in biologically homologous complex
      with eubacterial ribosome reveals its chaperone action.
AB  - Trigger factor (TF), the first chaperone in eubacteria to encounter the emerging
      nascent chain, binds to the large ribosomal subunit in the vicinity of the
      protein exit tunnel opening and forms a sheltered folding space. Here, we present
      the 3.5-A crystal structure of the physiological complex of the large ribosomal
      subunit from the eubacterium Deinococcus radiodurans with the N-terminal domain
      of TF (TFa) from the same organism. For anchoring, TFa exploits a small ribosomal
      surface area in the vicinity of proteins L23 and L29, by using its "signature
      motif" as well as additional structural elements. The molecular details of TFa
      interactions reveal that L23 is essential for the association of TF with the
      ribosome and may serve as a channel of communication with the nascent chain
      progressing in the tunnel. L29 appears to induce a conformational change in TFa,
      which results in the exposure of TFa hydrophobic patches to the opening of the
      ribosomal exit tunnel, thus increasing its affinity for hydrophobic segments of
      the emerging nascent polypeptide. This observation implies that, in addition to
      creating a protected folding space for the emerging nascent chain, TF association
      with the ribosome prevents aggregation by providing a competing hydrophobic
      environment and may be critical for attaining the functional conformation
      necessary for chaperone activity.

PMID- 16091461
TI  - Monitoring disease progression in transgenic mouse models of Alzheimer's disease
      with proton magnetic resonance spectroscopy.
AB  - Currently no definitive biomarker of Alzheimer's disease (AD) is available, and
      this impedes both clinical diagnosis in humans and drug discovery in transgenic
      animal models. Proton magnetic resonance spectroscopy ((1)H MRS) provides a
      noninvasive way to investigate in vivo neurochemical abnormalities. Each
      observable metabolite can potentially provide information about unique in vivo
      pathological processes at the molecular or cellular level. In this study, the age
      dependent 1H MRS profile of transgenic AD mice was compared to that of wild-type
      mice. Twenty-seven APP-PS1 mice (which coexpress mutated human presenilin 1 and
      amyloid-beta precursor protein) and 30 wild-type mice age 66-904 days were
      examined, some repeatedly. A reduction in the levels of N-acetylaspartate and
      glutamate, compared with total creatine levels, was found in APP-PS1 mice with
      advancing age. The most striking finding was a dramatic increase in the
      concentration of myo-inositol with age in APP-PS1 mice, which was not observed in
      wild-type mice. The age-dependent neurochemical changes observed in APP-PS1 mice
      agree with results obtained from in vivo human MRS studies. Among the different
      transgenic mouse models of AD that have been studied with 1H MRS, APP-PS1 mice
      seem to best match the neurochemical profile exhibited in human AD. 1H MRS could
      serve as a sensitive in vivo surrogate indicator of therapeutic efficacy in
      trials of agents designed to reduce neurotoxicity due to microglial activation.
      Because of its noninvasive and repeatable nature, MRS in transgenic models of AD
      could substantially accelerate drug discovery for this disease.

PMID- 16091462
TI  - The electroosmotic droplet switch: countering capillarity with electrokinetics.
AB  - Electroosmosis, originating in the double-layer of a small liquid-filled pore
      (size R) and driven by a voltage V, is shown to be effective in pumping against
      the capillary pressure of a larger liquid droplet (size B) provided the
      dimensionless parameter sigmaR(2)/epsilon|zeta|VB is small enough. Here sigma is
      surface tension of the droplet liquid/gas interface, epsilon is the liquid
      dielectric constant, and zeta is the zeta potential of the solid/liquid pair. As
      droplet size diminishes, the voltage required to pump electroosmotically scales
      as V approximately R(2)/B. Accordingly, the voltage needed to pump against
      smaller higher-pressure droplets can actually decrease provided the pump poresize
      scales down with droplet size appropriately. The technological implication of
      this favorable scaling is that electromechanical transducers made of moving
      droplets, so-called "droplet transducers," become feasible. To illustrate, we
      demonstrate a switch whose bistable energy landscape derives from the surface
      energy of a droplet-droplet system and whose triggering derives from the
      electroosmosis effect. The switch is an electromechanical transducer
      characterized by individual addressability, fast switching time with low voltage,
      and no moving solid parts. We report experimental results for millimeter-scale
      droplets to verify key predictions of a mathematical model of the switch. With
      millimeter-size water droplets and micrometer-size pores, 5 V can yield switching
      times of 1 s. Switching time scales as B(3)/VR(2). Two possible "grab-and
      release" applications of arrays of switches are described. One mimics the
      controlled adhesion of an insect, the palm beetle; the other uses wettability to
      move a particle along a trajectory.

PMID- 16091463
TI  - A map of the human genome in linkage disequilibrium units.
AB  - Two genetic maps with additive distances contribute information about
      recombination patterns, recombinogenic sequences, and discovery of genes
      affecting a particular phenotype. Recombination is measured in morgans (w) over a
      single generation in a linkage map but may cover thousands of generations in a
      linkage disequilibrium (LD) map measured in LD units (LDU). We used a subset of
      single nucleotide polymorphisms from the HapMap Project to create a genome-wide
      map in LDU. Recombination accounts for 96.8% of the LDU variance in chromosome
      arms and 92.4% in their deciles. However, deeper analysis shows that LDU/w, an
      estimate of the effective bottleneck time (t), is significantly variable among
      chromosome arms because (i) the linkage map is approximated from the Haldane
      function, then adjusted toward the Kosambi function that is more accurate but
      still exaggerates w for all chromosomes, especially shorter ones; (ii) the non
      pseudoautosomal region of the X chromosome is subject to hemizygous selection;
      and (iii) at resolution less than approximately 40,000 markers per w, there are
      indeterminacies (holes) in the LD map reflecting intervals of very high
      recombination. Selection and stochastic variation in small regions must have
      effects, which remain to be investigated by comparisons among populations. These
      considerations suggest an optimal strategy to eliminate holes quickly, greatly
      enhance the resolution of sex-specific linkage maps, and maximize the gain in
      association mapping by using LD maps.

PMID- 16091464
TI  - Centromere renewal and replacement in the plant kingdom.

PMID- 16091465
TI  - The metabolic basis of whole-organism RNA and phosphorus content.
AB  - Understanding the storage, flux, and turnover of nutrients in organisms is
      important for quantifying contributions of biota to biogeochemical cycles. Here
      we present a model that predicts the storage of phosphorus-rich RNA and whole
      body phosphorus content in eukaryotes based on the mass- and temperature
      dependence of ATP production in mitochondria. Data from a broad assortment of
      eukaryotes support the model's two main predictions. First, whole-body RNA
      concentration is proportional to mitochondrial density and consequently scales
      with body mass to the -1/4 power. Second, whole-body phosphorus content declines
      with increasing body mass in eukaryotic unicells but approaches a relatively
      constant value in large multicellular animals because the fraction of phosphorus
      in RNA decreases relative to the fraction in other pools. Extension of the model
      shows that differences in the flux of RNA-associated phosphorus are due to the
      size dependencies of metabolic rate and RNA concentration. Thus, the model
      explicitly links two biological currencies at the individual level: energy in the
      form of ATP and materials in the form of phosphorus, both of which are critical
      to the functioning of ecosystems. The model provides a framework for linking
      attributes of individuals to the storage and flux of phosphorus in ecosystems.

PMID- 16091466
TI  - Kinship-based politics and the optimal size of kin groups.
AB  - Kin form important political groups, which change in size and relative inequality
      with demographic shifts. Increases in the rate of population growth increase the
      size of kin groups but decrease their inequality and vice versa. The optimal size
      of kin groups may be evaluated from the marginal political product (MPP) of their
      members. Culture and institutions affect levels and shapes of MPP. Different
      optimal group sizes, from different perspectives, can be suggested for any MPP
      schedule. The relative dominance of competing groups is determined by their MPP
      schedules. Groups driven to extremes of sustainability may react in Malthusian
      fashion, including fission and fusion, or in Boserupian fashion, altering social
      technology to accommodate changes in size. The spectrum of alternatives for
      actors and groups, shaped by existing institutions and natural and cultural
      selection, is very broad. Nevertheless, selection may result in survival of
      particular kinds of political structures.

PMID- 16091467
TI  - Isolation of a rice regeneration quantitative trait loci gene and its application
      to transformation systems.
AB  - Regeneration of plant organs is often the essential step in genetic
      transformation; however, the regeneration ability of a plant varies depending on
      the genetic background. By conventional crosses of low-regeneration rice strain
      Koshihikari with high-regeneration rice strain Kasalath, we identified some
      quantitative trait loci, which control the regeneration ability in rice. Using a
      map-based cloning strategy, we isolated a main quantitative trait loci gene
      encoding ferredoxin-nitrite reductase (NiR) that determines regeneration ability
      in rice. Molecular analyses revealed that the poor regeneration ability of
      Koshihikari is caused by lower expression than in Kasalath and the specific
      activity of NiR. Using the NiR gene as a selection marker, we succeeded in
      selectively transforming a foreign gene into rice without exogenous marker genes.
      Our results demonstrate that nitrate assimilation is an important process in rice
      regeneration and also provide an additional selectable marker for rice
      transformation.

PMID- 16091468
TI  - Fractal intermediates in the self-assembly of silicatein filaments.
AB  - Silicateins are proteins with catalytic, structure-directing activity that are
      responsible for silica biosynthesis in certain sponges; they are the constituents
      of macroscopic protein filaments that are found occluded within the silica
      needles made by Tethya aurantia. Self-assembly of the silicatein monomers and
      oligomers is shown to form fibrous structures by a mechanism that is
      fundamentally different from any previously described filament-assembly process.
      This assembly proceeds through the formation of diffusion-limited, fractally
      patterned aggregates on the path to filament formation. The driving force for
      this self-assembly is suggested to be entropic, mediated by the interaction of
      hydrophobic patches on the surfaces of the silicatein subunits that are not found
      on highly homologous congeners that do not form filaments. Our results are
      consistent with a model in which silicatein monomers associate into oligomers
      that are stabilized by intermolecular disulfide bonds. These oligomeric units
      assemble into a fractal network that subsequently condenses and organizes into a
      filamentous structure. These results represent a potentially general mechanism
      for protein fiber self-assembly.

PMID- 16091469
TI  - CD1d ligation on human monocytes directly signals rapid NF-kappaB activation and
      production of bioactive IL-12.
AB  - Natural killer T cells (NKT cells) expressing a semi-invariant CD1d-reactive T
      cell receptor (invariant NKT, iNKT) can be rapidly activated by monocytes or
      immature dendritic cells (iDCs) bearing a CD1d-presented glycolipid antigen and
      can in turn stimulate these myeloid cells to mature and produce IL-12. Previous
      studies have shown that iNKT-produced IFNgamma and CD40 ligand contribute to this
      dendritic cell maturation. This study demonstrates that CD1d ligation alone, in
      the absence of iNKT, could rapidly (within 24 h) stimulate production of
      bioactive IL-12p70 by CD1d+ human peripheral blood monocytes as well as iDCs.
      IFNgamma alone had no effect, but it markedly enhanced CD1d-stimulated IL-12
      production. Monocyte differentiation, as assessed by CD40 and CD1a up-regulation,
      was also accelerated by CD1d stimulation, consistent with this representing a
      physiological response. CD1d ligation on the human monocytic cell line THP-1
      similarly specifically stimulated IL-12 production. Biochemical studies showed
      that IL-12 release correlated with rapid phosphorylation of IkappaB, a critical
      step in NF-kappaB activation. Selective NF-kappaB inhibition blocked this CD1d
      stimulated IL-12 production. Finally, CD1d ligation could also enhance IL-12
      production in the presence of suboptimal LPS or CD40 stimulation. These findings
      demonstrate an innate immune signaling function for CD1d and provide a mechanism
      for the rapid activation of monocytes and iDCs by CD1d-reactive T cells.

PMID- 16091470
TI  - Ubiquitin at Fox Chase.

PMID- 16091471
TI  - NKG2D-independent suppression of T cell proliferation by H60 and MICA.
AB  - The activating receptor NKG2D recognizes a wide range of different ligands, some
      of which are primarily expressed in "stressed" tissues or on tumor cells. Until
      now, similar stimulatory effects on natural killer and CD8+ T cells have been
      described for all NKG2D ligands, and the NKG2D receptor/ligand system has
      therefore been interpreted as a sensor system involved in tumor immune
      surveillance and activation of immune responses. We show here that the NKG2D
      ligands H60 and MIC class 1 chain-related protein A (MICA) can also mediate
      strong suppressive effects on T cell proliferation. Responsiveness to H60- and
      MICA-mediated suppression requires IL-10 and involves a receptor other than
      NKG2D. These findings might provide explanations for the observation that strong
      in vivo NKG2D ligand expression, such as that on tumor cells, sometimes fails to
      support effective immune responses and links this observation to a distinct
      subgroup of NKG2D ligands.

PMID- 16091472
TI  - Coevolution between nonhomologous but functionally similar proteins and their
      conserved partners in the Legionella pathogenesis system.
AB  - Legionella pneumophila, the causative agent of Legionnaires' disease, and other
      pathogenic Legionella species multiply inside protozoa and human macrophages by
      using the intracellular multiplication (Icm)/defect in organelle trafficking
      (Dot) type-IV secretion system. The IcmQ protein, which possesses pore-forming
      activity, and IcmR, which regulates the IcmQ activity, are two essential
      components of this system. Analysis of the region expected to contain these two
      genes from 29 Legionella species revealed the presence of a conserved icmQ gene
      and a large hypervariable gene family [functional homologues of icmR (fir)
      genes], located at the icmR genomic position. Although hypervariable in their
      sequence, the fir genes from all 29 Legionella species were found, together with
      their corresponding icmQ genes, to function similarly during infection. In
      addition, all FIR proteins we examined were found to interact with their
      corresponding IcmQ proteins. Detailed bioinformatic, biochemical, and genetic
      analysis of the interaction between the variable FIR proteins and conserved IcmQ
      proteins revealed that their interaction depends on a variable region located
      between two conserved domains of IcmQ. This variable region was also found to be
      critical for IcmQ self-interaction, and the region probably coevolved with the
      corresponding FIR protein. A FIR-IcmQ pair was also found in Coxiella burnetii,
      the only known non-Legionella bacterium that contains an Icm/Dot system,
      indicating the significance of this protein pair for the function of this type-IV
      secretion system. We hypothesize that this gene variation, which is probably
      mediated by positive selection, plays an important role in the evolutionary arms
      race between the protozoan host cell and the pathogen.

PMID- 16091473
TI  - Efficient delivery of small interfering RNA to bone-metastatic tumors by using
      atelocollagen in vivo.
AB  - Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly
      becoming a powerful tool for genetic analysis and represents a potential strategy
      for therapeutic product development. However, there are no reports of systemic
      delivery for siRNAs toward treatment of bone-metastatic cancer. Accordingly, we
      report here that i.v. injection of GL3 luciferase siRNA complexed with
      atelocollagen showed effective reduction of luciferase expression from bone
      metastatic prostate tumor cells developed in mouse thorax, jaws, and/or legs. We
      also show that the siRNA/atelocollagen complex can be efficiently delivered to
      tumors 24 h after injection and can exist intact at least for 3 days.
      Furthermore, atelocollagen-mediated systemic administration of siRNAs such as
      enhancer of zeste homolog 2 and phosphoinositide 3'-hydroxykinase p110-alpha
      subunit, which were selected as candidate targets for inhibition of bone
      metastasis, resulted in an efficient inhibition of metastatic tumor growth in
      bone tissues. In addition, upregulation of serum IL-12 and IFN-alpha levels was
      not associated with the in vivo administration of the siRNA/atelocollagen
      complex. Thus, for treatment of bone metastasis of prostate cancer, an
      atelocollagen-mediated systemic delivery method could be a reliable and safe
      approach to the achievement of maximal function of siRNA.

PMID- 16091474
TI  - Egr3 stimulation of GABRA4 promoter activity as a mechanism for seizure-induced
      up-regulation of GABA(A) receptor alpha4 subunit expression.
AB  - GABA is the major inhibitory transmitter at CNS synapses. Changes in subunit
      composition of the pentameric GABA(A) receptor, including increased levels of
      alpha4 subunit in dentate granule cells and associated functional alterations
      such as increased zinc blockade of GABA currents, are hypothesized to be critical
      components of epileptogenesis. Here, we report that the minimal promoter of the
      human alpha4 subunit gene (GABRA4p), when used to drive reporter gene expression
      from adeno-associated viral vectors, controls condition-specific up-regulation in
      response to status epilepticus, defining a transcriptional mechanism for seizure
      induced changes in levels of alpha4 subunit containing GABA(A) receptors.
      Transfection studies in primary hippocampal neurons show that inducible early
      growth response factor 3 (Egr3) up-regulates GABRA4p activity as well as the
      levels of endogenous alpha4 subunits. Given that Egr3 knockout mice display
      approximately 50% less GABRA4 mRNAs in the hippocampus and that increases in
      alpha4 and Egr3 mRNAs in response to pilocarpine-induced status epilepticus are
      accompanied by increased binding of Egr3 to GABRA4 in dentate granule cells, our
      findings support a role for Egr3 as a major regulator of GABRA4 in developing
      neurons and in epilepsy.

PMID- 16091475
TI  - Pooled association genome scanning: validation and use to identify addiction
      vulnerability loci in two samples.
AB  - Association genome scanning is of increasing interest for identifying the
      chromosomal regions that contain gene variants that contribute to vulnerability
      to complex disorders, including addictions. To improve the power and feasibility
      of this approach, we have validated "10k" microarray-based allelic frequency
      assessments in pooled DNA samples and have used this approach to seek allelic
      frequency differences between heavy poly-substance abusers and well characterized
      control individuals. Thirty-eight loci contain SNPs that display robust allele
      frequency differences between abusers and controls in both European- and African
      American samples. These loci identify an alcohol/acetaldehyde dehydrogenase gene
      cluster and genes implicated in cellular signaling, gene regulation, development,
      "cell adhesion," and Mendelian disorders. The results converge with previous
      linkage and association results for addictions. Pooled association genome
      scanning provides a useful tool for elucidating molecular genetic underpinnings
      of complex disorders and identifies both previously understood and previously
      unanticipated mechanisms for addiction vulnerability.

PMID- 16091476
TI  - Proteomic analysis of formalin-fixed prostate cancer tissue.
AB  - Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissue would enable
      retrospective biomarker investigations of this vast archive of pathologically
      characterized clinical samples that exist worldwide. These FFPE tissues are,
      however, refractory to proteomic investigations utilizing many state of the art
      methodologies largely due to the high level of covalently cross-linked proteins
      arising from formalin fixation. A novel tissue microdissection technique has been
      developed and combined with a method to extract soluble peptides directly from
      FFPE tissue for mass spectral analysis of prostate cancer (PCa) and benign
      prostate hyperplasia (BPH). Hundreds of proteins from PCa and BPH tissue were
      identified, including several known PCa markers such as prostate-specific
      antigen, prostatic acid phosphatase, and macrophage inhibitory cytokine-1.
      Quantitative proteomic profiling utilizing stable isotope labeling confirmed
      similar expression levels of prostate-specific antigen and prostatic acid
      phosphatase in BPH and PCa cells, whereas the expression of macrophage inhibitory
      cytokine-1 was found to be greater in PCa as compared with BPH cells.

PMID- 16091477
TI  - Cyclooxygenase-2 inhibitors reverse chemoresistance phenotype in medullary
      thyroid carcinoma by a permeability glycoprotein-mediated mechanism.
AB  - OBJECTIVE: Medullary thyroid carcinoma (MTC) is a highly chemoresistant malignant
      neoplasia deriving from parafollicular C cells. Chemotherapy failure has been
      ascribed, at least in part, to the overexpression by MTC of the multidrug
      resistance 1 (MDR1) gene, encoding a transmembrane glycoprotein [permeability
      glycoprotein (P-gp)] that antagonizes intracellular accumulation of cytotoxic
      agents. P-gp expression and function in a rat model have been demonstrated to
      depend on cyclooxygenase (COX)-2 isoform levels, which are found elevated in many
      human cancers. The aim of our study was to investigate the role of the COX-2
      pathway in modulating chemoresistance. DESIGN AND RESULTS: We investigated P-gp
      and COX-2 expression and then evaluated the sensitizing effects of COX-2
      inhibitors on the cytotoxic effects of doxorubicin in the presence or in the
      absence of prostaglandin E2 in primary cultures and in a human MTC cell line, TT.
      Moreover, P-gp function has been studied. Our data show that TT cells express
      both MDR1 and COX-2 and that rofecoxib, a selective COX-2 inhibitor, sensitizes
      TT cells to the cytotoxic effects of doxorubicin, reducing P-gp expression and
      function. CONCLUSIONS: Our data suggest that these effects are mediated by a
      mechanism not involving the generation of prostaglandin E2, possibly implicating
      the synthesis of other COX-2 products.

PMID- 16091478
TI  - Estrogen replacement in women of fertile years with hypopituitarism.
AB  - BACKGROUND: What form of estrogen to prescribe a young hypopituitary woman with
      gonadal failure remains an open question despite evidence that oral estrogen
      therapy induces GH resistance and an increase in fat mass. METHODS: Using an
      international surveillance study of hypopituitary patients, we examined two
      questions: 1) What estrogen is prescribed to young women of fertile years with
      hypopituitarism? 2) Is there a difference in body composition or IGF-I levels
      dependent on the type of estrogen prescribed? RESULTS: Six hundred twenty-eight
      GH-deficient women, aged 18-50 yr, were identified. Three hundred thirteen had
      normal gonadal function, and 315 were receiving estrogen therapy; of these 14%
      were using transdermal estradiol, and 86% were taking an oral estrogen
      preparation (38% oral estradiol, 18% conjugated estrogens, and 30% ethinyl
      estradiol in the oral contraceptive). There was no difference in weight,
      waist/hip ratio, or body composition between the women taking different estrogen
      therapies. However, if the oral estrogen groups were combined, they showed less
      change in waist and hip measurement and had a greater waist/hip ratio after 1 yr
      of GH treatment compared with patients with normal gonadal function (0.85 vs.
      0.83; P = 0.022). Patients taking ethinyl estradiol had lower age-adjusted IGF-I
      sd scores and required almost twice the GH dose to achieve an IGF-I sd score that
      remained lower than patients with normal gonadal function and patients receiving
      transdermal estradiol. CONCLUSIONS: 1) The majority of women of fertile years
      with hypo-pituitarism take oral estrogen replacement therapy. 2) Waist/hip ratio
      was greater in women taking oral estrogens, and there is indirect evidence that
      oral estrogens reduce the action of GH on fat mass. 3) Patients using the oral
      contraceptive had lower IGF-I levels and required twice the GH dose compared with
      patients receiving transdermal estradiol.

PMID- 16091479
TI  - Epicardial adipose tissue and insulin resistance in obese subjects.
AB  - CONTEXT: Epicardial adipose tissue has been recently recognized as a source of
      bioactive molecules as well as free fatty acids, adiponectin, and inflammatory
      cytokines. Epicardial fat reflects intraabdominal visceral fat, and the
      echocardiographic assessment of this tissue is an easy and reliable marker of
      visceral adiposity. OBJECTIVE: In this study we evaluated whether epicardial
      adipose tissue is related to insulin sensitivity and glucose metabolism in obese
      subjects. PATIENTS: Thirty obese subjects (20 women and 10 men; mean age, 40.8 +/
      11.5 yr; body mass index, 43 +/- 9.1 kg/m2) were included in this study. No
      subject was taking drugs or had a history or evidence of metabolic,
      cardiovascular, respiratory, or hepatic disease. MAIN OUTCOME MEASURES: Each
      subject underwent a transthoracic echocardiogram to evaluate epicardial adipose
      tissue thickness, a euglycemic hyperinsulinemic clamp to estimate insulin
      sensitivity, and an oral glucose tolerance test to evaluate glucose tolerance.
      RESULTS: The thickness of the epicardial adipose tissue on the right ventricle
      varied between 4 and 17.4 mm. Echocardiographic epicardial adipose tissue was
      significantly correlated with whole-body glucose uptake index from the clamp and
      with all indices of insulin resistance and glucose intolerance measured, except
      the 120-min plasma glucose level after an oral glucose tolerance test.
      CONCLUSIONS: Our study showed that the epicardial fat is significantly related to
      obesity-related insulin resistance. This finding could be of potential interest
      in clinical practice and research of obesity-related risk stratification.

PMID- 16091480
TI  - Children with differentiated thyroid cancer achieve adequate hyperthyrotropinemia
      within 14 days of levothyroxine withdrawal.
AB  - CONTEXT: The preparation for radioiodine administration recommended by the
      current pediatric literature is a 6-wk withdrawal that typically includes the
      transient administration of T3. Compared with adults, T4 clearance rates and
      serum TSH to free T4 ratios are higher in children, implying that pediatric
      patients can achieve adequate hyperthyrotropinemia with shorter levothyroxine
      withdrawals. OBJECTIVE: The objective of this study was to determine whether
      children with differentiated thyroid cancer achieve adequate hyperthyrotropinemia
      using an abbreviated levothyroxine withdrawal protocol. DESIGN: The study design
      was a retrospective analysis of 15 consecutive levothyroxine withdrawals
      performed without T3 at Children's Hospital Boston. PATIENTS: Eleven children
      with differentiated thyroid cancer were included. The average age at the time of
      withdrawal was 12.5 +/- 0.8 yr. MAIN OUTCOME MEASUREMENT: Serum TSH
      concentrations obtained after the discontinuation of levothyroxine were analyzed
      to determine the time interval required to achieve a serum TSH level greater than
      25 microU/ml for each patient. RESULTS: Adequate hyperthyrotropinemia was
      documented in all children tested by d 14. The mean interval required to achieve
      a serum TSH level above 25 microU/ml from a suppressed serum TSH was 12.3 +/- 0.7
      d. CONCLUSIONS: Shorter withdrawals minimize hypothyroid morbidity and the
      theoretical risk of decreased 131micro)I residence time from excessive
      hyperthyrotropinemia. These benefits are amplified in children due to their high
      incidence of distant metastases. We propose an abbreviated 2-wk withdrawal
      protocol to facilitate the adjunctive therapy and surveillance of children with
      follicular cell-derived cancers.

PMID- 16091481
TI  - Comparison of apolipoprotein B100 metabolism between continuous subcutaneous and
      intraperitoneal insulin therapy in type 1 diabetes.
AB  - OBJECTIVE: In type 1 diabetic patients, the replacement of s.c. insulin infusion
      with i.p. insulin infusion restores the normal physiological gradient between the
      portal vein and the peripheral circulation, which is likely to modify lipoprotein
      metabolism. DESIGN: To check this hypothesis, we performed two apolipoprotein
      (apo) B100 kinetic studies in seven type 1 diabetic patients, first under s.c.
      insulin infusion and then 3 months after the beginning of i.p. insulin infusion.
      RESULTS: Glycemic control was similar under s.c. insulin infusion and i.p.
      insulin infusion, as assessed by glycated hemoglobin A1c and the capillary
      glycemic curve determined during the kinetic study. Very low-density and
      intermediate-density lipoprotein apoB100 pool size, production rate, and
      fractional catabolic rate (FCR) were similar under s.c. insulin infusion and i.p.
      insulin infusion. The low-density lipoprotein apoB100 FCR tended to decrease
      under ip insulin (0.45 +/- 0.06 vs. 0.55 +/- 0.11 pool/d), but the difference did
      not reach statistical significance (95% confidence interval for the difference, 
      0.33, 0.11). The low-density lipoprotein apoB100 pool size and production rate
      remained unchanged under i.p. insulin infusion compared with s.c. insulin
      infusion. CONCLUSION: In type 1 diabetic patients, the replacement of s.c.
      insulin infusion with i.p. insulin infusion does not induce profound
      modifications of apoB100-containing lipoprotein production and FCRs.

PMID- 16091482
TI  - Effects of dietary weight loss on sympathetic activity and cardiac risk factors
      associated with the metabolic syndrome.
AB  - CONTEXT: Weight reduction, the first line treatment for the metabolic syndrome,
      improves insulin sensitivity and associated metabolic and cardiovascular
      abnormalities, but there is a paucity of data regarding its effect on sympathetic
      nervous system (SNS) activity in this clinical setting. OBJECTIVES: The
      objectives of this study were to test the hypothesis that dietary weight loss
      attenuates both insulin resistance and SNS activity and to examine the
      relationships between SNS activity and metabolic syndrome (MetS) components.
      DESIGN: This was a single-sample, repeated measures design study. SETTING: This
      study was performed at a tertiary referral center. PARTICIPANTS: Twenty-three
      MetS subjects (age, 58 +/- 2 yr; body mass index, 33.3 +/- 0.8 kg/m2; mean +/-
      sem) were studied. INTERVENTION: A hypocaloric modified Dietary Approaches to
      Stop Hypertension diet (26% fat, 22% protein, and 51% carbohydrate; 100 mmol/d
      sodium) was consumed for 3 months. MAIN OUTCOME MEASURES: The main outcome
      measures were postganglionic muscle sympathetic nerve activity (microneurography
      at a peroneal nerve), whole-body plasma norepinephrine spillover rate,
      spontaneous cardiac baroreflex function, and insulin sensitivity. RESULTS: The
      hypocaloric diet significantly reduced body weight by 7% and improved all MetS
      components. Norepinephrine spillover decreased from 877 +/- 180 to 503 +/- 39
      ng/min (P = 0.005), and muscle sympathetic nerve activity decreased from 40.6 +/-
      2.1 to 34.6 +/- 2.4 bursts/min (P = 0.01), whereas cardiac baroreflex sensitivity
      increased by 23.0 +/- 8.0% (P = 0.02). The change in the norepinephrine spillover
      rate correlated positively and independently with the change in plasma leptin
      concentration (r = 0.49; P = 0.03). CONCLUSION: Weight loss by a hypocaloric diet
      with moderate sodium restriction diminishes SNS activity in MetS subjects. This
      may be due to the consequences of decreased leptin concentration, enhanced
      insulin sensitivity, or improvements in cardiac baroreflex function.

PMID- 16091483
TI  - Genotypes at 11beta-hydroxysteroid dehydrogenase type 11B1 and hexose-6-phosphate
      dehydrogenase loci are not risk factors for apparent cortisone reductase
      deficiency in a large population-based sample.
AB  - CONTEXT: Apparent cortisone reductase deficiency (ACRD) is a rarely ascertained
      condition characterized by signs of androgen excess in women or children and
      decreased urinary excretion of cortisol metabolites compared with cortisone
      metabolites. These findings suggest a deficiency of 11beta-hydroxysteroid
      dehydrogenase type 1 (11-HSD1; encoded by the HSD11B1 gene), which normally
      converts cortisone to cortisol. Common polymorphisms in both HSD11B1 and the
      hexose-6-phosphate dehydrogenase (H6PD) gene encoding hexose-6-phosphate
      dehydrogenase have been found together in ACRD patients, who carry three of a
      possible four minor alleles at the two loci. OBJECTIVE: The objective of this
      study was to confirm the postulated digenic inheritance mechanism for ACRD.
      DESIGN: This was a population-based association study (Dallas Heart Study).
      Subjects were genotyped for the 1971T>G polymorphism in intron 3 of HSD11B1 and
      the R453Q polymorphism in H6PD. SUBJECTS: The study comprised 3551 individuals in
      a population-based sample (50% black, 35% white, and 15% Hispanic). MAIN OUTCOME
      MEASURE: The main outcome measure was association between genotypes and risk for
      polycystic ovarian syndrome. RESULTS: Both polymorphisms occurred more frequently
      than previously reported. Thus, ACRD genotypes (at least three of four minor
      alleles) occurred in 7.0% of subjects. There were no associations between
      genotype and body mass index; waist/hip ratio; visceral adiposity; measures of
      insulin sensitivity; levels of testosterone, FSH, or LH (in females); or risk of
      polycystic ovarian syndrome. There was no genotype effect on urinary free
      cortisol/cortisone or corticosteroid metabolite ratios, which were measured in 10
      subjects, each carrying zero, three, or four minor alleles. CONCLUSIONS:
      Previously reported associations of ACRD with HSD11B1 and H6PD alleles represent
      ascertainment bias. However, rare severe mutations in these genes cannot be ruled
      out.

PMID- 16091484
TI  - Sex steroid metabolism in human peripheral blood mononuclear cells changes with
      aging.
AB  - CONTEXT: Dehydroepiandrosterone (DHEA) mainly exerts indirect action via
      downstream conversion toward sex steroids within peripheral target cells
      including immune cells. In vitro DHEA has been shown to enhance IL-2 release from
      T lymphocytes, whereas it inhibits IL-6 secretion. Conversely, aging is
      associated with a decline in both DHEA and IL-2, whereas IL-6 increases.
      OBJECTIVE: The objective of the study was to investigate age-related differences
      in expression and functional activity of steroidogenic enzymes involved in
      downstream conversion of DHEA in peripheral blood mononuclear cells (PBMCs).
      DESIGN: This study was cross-sectional. PARTICIPANTS/SETTING: Healthy young men
      (n = 8; age range, 23-29 yr) and healthy middle-aged men (n = 8; age range, 52-66
      yr) were studied in an academic setting. MEASURES: mRNA expression of
      steroidogenic enzymes in PBMCs was measured by qualitative and quantitative RT
      PCR analysis and enzyme activity assays after incubation of PBMCs with
      radiolabeled DHEA, 4-androstene-3,17-dione (androstenedione), and testosterone.
      RESULTS: RT-PCR analysis showed expression of all enzymes required for DHEA
      conversion toward active androgens and to the immune-stimulatory metabolite
      androstenediol. Steroid conversion patterns indicated a particularly increased
      activity of 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD5) in the older
      men, demonstrated by significantly higher conversion rates of DHEA to
      androstenediol and of androstenedione to testosterone (all P < 0.05). By
      contrast, conversion of DHEA to androstenedione via 3beta-HSD occurred at a
      similar rate. Quantitative RT-PCR analysis revealed increased expression of
      17beta-HSD 5 mRNA in PBMCs from the older men. CONCLUSIONS: Our results provide
      evidence for significant changes in sex steroid metabolism by human PBMCs with
      aging, which may represent an endocrine link to immune senescence.

PMID- 16091485
TI  - Distinctive inhibitory mechanisms of age and relative visceral adiposity on
      growth hormone secretion in pre- and postmenopausal women studied under a
      hypogonadal clamp.
AB  - BACKGROUND: Aging, body composition, and sex steroids jointly determine GH
      production. However, the actions of any given factor are confounded by the
      effects of the other two. HYPOTHESIS: Age and abdominal visceral fat (AVF) mass
      govern GH secretion via individually distinctive mechanisms, which can be
      unmasked by short-term sex steroid deprivation. DESIGN/SUBJECTS: In a university
      setting, healthy pre- and postmenopausal volunteers underwent GnRH agonist
      induced down-regulation for 6 wk to deplete ovarian sex steroids. GH secretion
      was evaluated by frequent blood sampling, saline vs. dual secretagogue infusions,
      an irregularity statistic, variable waveform deconvolution analysis, and a
      simplified feedback model. Computerized tomography was used to estimate AVF mass.
      OUTCOMES/MEASURES: In the sex steroid-deficient milieu, postmenopausal compared
      with premenopausal women exhibited 1) lower concentrations of IGF-I (P = 0.028)
      and GH (P < 0.05); 2) reduced pulsatile, but elevated basal, GH secretion (P <
      0.05); 3) more irregular GH patterns (P = 0.027); 4) an attenuated GH response to
      simultaneous GHRH/GH-releasing peptide-2 stimulation (P < 0.01); and 5) more
      rapid onset of GH release within secretory bursts (P < 0.01). In contrast, AVF
      negatively forecast GH responses to L-arginine/GH-releasing peptide-2 (r2= 0.45;
      P < 0.001) and L-arginine/GHRH (r2= 0.57; P = 0.007). From these marked
      contrasts, model-based analyses predicted distinguishable mechanisms by which
      aging and AVF alter pulsatile GH production. CONCLUSION: Under limited
      confounding by sex steroids, age and body composition modulate GH secretion via
      highly selective peptidyl pathways in healthy women.

PMID- 16091486
TI  - The metabolic syndrome, insulin resistance, and cardiovascular risk in diabetic
      and nondiabetic patients.
AB  - CONTEXT: The contribution of insulin resistance per se to the vascular risk
      conferred by the metabolic syndrome (MetS) is not known; conversely, it is
      uncertain whether insulin resistance confers vascular risk beyond the entity of
      the MetS. OBJECTIVE: The objective of this study was to investigate the impact of
      the MetS (Adult Treatment Panel III criteria) and insulin resistance (as
      estimated by the homeostasis model assessment index) on the incidence of vascular
      events. DESIGN AND PATIENTS: This was a prospective cohort study enrolling 750
      consecutive patients undergoing coronary angiography for the evaluation of
      coronary artery disease. SETTING: The study was performed at a tertiary care
      clinical research center. MAIN OUTCOME MEASURE: The main outcome measure was the
      incidence of vascular events over 2.3 yr. RESULTS: Both the MetS and insulin
      resistance predicted vascular events after controlling for non-MetS risk factors
      [hazard ratio (HR), 2.74 (95% confidence interval, 1.71-4.39; P < 0.001) and 1.51
      (1.24-1.84; P < 0.001), respectively]. After additional adjustment for insulin
      resistance, the MetS remained significantly predictive of vascular events [HR,
      2.69 (1.57-4.64); P < 0.001], and conversely, insulin resistance remained
      significantly predictive of vascular events despite adjustment for the MetS
      [standardized HR, 1.41 (1.14-1.75); P = 0.002]. Additional adjustment for the
      presence of type 2 diabetes revealed that both the MetS [adjusted HR, 2.57 (1.47
      4.51); P = 0.001] and homeostasis model assessment of insulin resistance
      [standardized adjusted HR, 1.37 (1.09-1.73); P = 0.007] significantly predicted
      vascular events independent from diabetes status. CONCLUSIONS: Both the MetS and
      insulin resistance are strong and mutually independent predictors of vascular
      risk among angiographed coronary patients.

PMID- 16091487
TI  - Androgens are associated with hemostatic and inflammatory factors among women at
      the mid-life.
AB  - GOAL: The goal of this study was to relate annually measured endogenous androgens
      to hemostatic and inflammation markers in women longitudinally. METHODS: A total
      of 3302 participants from the Study of Women's Health Across the Nation, aged 42
      52 yr at baseline and self-identified as African-American (28%), Caucasian (47%),
      Chinese (8%), Hispanic (8%), or Japanese (9%) were evaluated for testosterone
      (T), dehydroepiandrosterone sulfate, and SHBG at four time points in 5 yr.
      Cardiovascular disease markers were fibrinogen, activated factor VII-c, C
      reactive protein (hsC-RP), and the fibrolytic factors, plasminogen activator
      inhibitor type 1 (PAI-1), and tissue plasminogen activator [t(PA)]. RESULTS: T
      and free androgen index (FAI) were associated highly positively with PAI-1 and
      t(PA), and FAI was associated highly and positively with hsC-RP. Lower SHBG
      levels, associated with greater bioavailable T, were associated significantly
      with higher levels of PAI-1, t(PA), hsC-RP, and factor VII-c. SHBG was lower in
      Chinese and Japanese women markedly, resulting in FAI values that, on average,
      were higher among Chinese and Japanese women compared with African-American,
      Caucasian, and Hispanic women. IMPLICATIONS: There were strong, positive
      associations of androgens with fibrolytic and inflammation markers, even after
      considering age, body size, smoking, and race/ethnicity. It is important to study
      androgens, their precursors, and their carrier protein as part of the risk
      profile for heart disease in mid-aged women.

PMID- 16091488
TI  - Inaccuracy of insulin-like growth factor (IGF) binding protein (IGFBP)-3
      assessment in the diagnosis of growth hormone (GH) deficiency from childhood to
      young adulthood: association to low GH dependency of IGF-II and presence of
      circulating IGFBP-3 18-kilodalton fragment.
AB  - CONTEXT: Poor sensitivity of IGF binding protein (IGFBP)-3 assessment in the work
      up of GH deficiency (GHD) has been ascribed to the equal affinity of IGFBP-3 for
      IGF-I and IGF-II and to IGFBP-3 proteolysis. OBJECTIVE: The objective of this
      study was to determine the IGF-II GH dependency and IGFBP-3 proteolysis in
      patients with GHD from childhood to young adulthood. DESIGN: This study was cross
      sectional. SETTING: This was a national multicenter study performed in university
      hospitals. PATIENTS: One hundred thirty-one subjects (chronological age, 1.3-25
      yr), 72 patients with GHD and 59 subjects with idiopathic short stature, were
      studied. INTERVENTIONS: IGF-I, IGF-II, and IGFBP-3 serum concentrations were
      measured by immunoradiometric assay. IGFBP-3 circulating forms were assessed by
      Western immunoblot (WIB) analysis. MAIN OUTCOME MEASURES: Main outcome measures
      were sensitivity and specificity of IGF-I, IGF-II, and IGFBP-3 measurements.
      RESULTS: Sensitivity and specificity of IGFBP-3 measurement were 27 and 100%,
      respectively. IGFBP-3 sensitivity was 46% in young adulthood. Sensitivity and
      specificity of IGF-I were 69 and 81%, respectively. Sensitivity and specificity
      of IGF-II assessment were 23 and 97%, respectively. IGFBP-3 WIB revealed the
      presence of the intact form and the major 29-kDa fragment in both GHD and
      subjects with idiopathic short stature. In patients with GHD, WIB showed the
      presence of an additional smaller IGFBP-3 fragment migrating at approximately 18
      kDa. CONCLUSIONS: Our results suggest that in children and young adults with GHD,
      the low GH dependency of IGF-II together with IGFBP-3 proteolytic activity
      yielding the 18-kDa fragment concur to reduce the sensitivity of IGFBP-3
      assessment, ultimately making it too inaccurate as a screening test in the work
      up of GHD.

PMID- 16091489
TI  - Expression of the antiapoptotic gene seladin-1 and octreotide-induced apoptosis
      in growth hormone-secreting and nonfunctioning pituitary adenomas.
AB  - CONTEXT: Seladin-1 (from selective Alzheimer's disease indicator-1) is a recently
      discovered gene that has been found to be down-regulated in brain regions
      affected by Alzheimer's disease. Seladin-1 effectively protects neurons against
      beta-amyloid-mediated toxicity and prevents apoptosis via inhibition of the
      activation of caspase-3, a key mediator of the apoptotic cascade. Although
      seladin-1 is expressed in the pituitary gland, no study addressed the expression
      or the function of this gene in pituitary adenomas. OBJECTIVE: The aim of the
      present study was to determine the expression level of the seladin-1 gene in
      pituitary tumors, i.e. GH-secreting and nonfunctioning pituitary adenomas (NFPA),
      and to determine whether differential expression might be associated with
      different somatostatin (sst)-induced apoptosis. RESULTS: We found by quantitative
      real-time RT-PCR that the expression level of seladin-1 was significantly higher
      in NFPA (n = 21) than in GH-secreting adenomas (n = 30; mean +/- se, 25.69 +/-
      6.39 vs. 8.02 +/- 2.68 pg/microg total RNA; P = 0.006). Although the amount of
      activated caspase-3 did not differ between the two groups of tumors, in primary
      cell cultures, octreotide was able to increase apoptosis, evaluated by the level
      of cleaved cytokeratin 18 and the presence of apoptotic nuclei, in GH-secreting
      adenomas, but not in NFPA. This different response was not attributable to
      differences in the amount of transcript of sst receptors 2 and 5, which was
      similar in the two groups of tumors. CONCLUSIONS: Our results suggest that
      differential seladin-1 expression in pituitary adenomas may be associated with a
      different apoptotic response to sst analogs.

PMID- 16091490
TI  - Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is
      believed to have a genetic basis. However, no specific susceptibility gene or
      region has been conclusively identified. OBJECTIVE: The objective of this study
      was to duplicate a previous study that localized a PCOS susceptibility region to
      chromosome 19p13.2 and to narrow the susceptibility region. DESIGN: This study
      was designed to test for genetic linkage and association between PCOS and short
      tandem repeat polymorphisms in 367 families, by analysis of linkage and family
      based association. SETTING: The study was conducted at academic medical centers.
      PATIENTS OR OTHER PARTICIPANTS: We studied 367 families of predominantly European
      origin with at least one PCOS patient. Families included 107 affected sibling
      (sister) pairs (ASPs) in 83 families, and 390 trios with both parents and an
      affected daughter. The data set comprises two independent groups. Set 1 consists
      of 44 ASPs and 163 trios. Set 2 consists of 63 ASPs and 227 trios.
      INTERVENTION(S): The intervention was the drawing of blood for DNA extraction.
      MAIN OUTCOME MEASURE: We employed measures of evidence for linkage and
      association between PCOS and 19 STRs. RESULTS: Linkage with PCOS was observed
      over a broad region of chromosome 19p13.2. The strongest evidence for association
      was observed with D19S884 (chi2 = 11.85; nominal P < 0.0006; permutation P =
      0.034) and duplicated our earlier findings. CONCLUSIONS: The present analysis
      suggests that a PCOS susceptibility locus maps very close to D19S884. Additional
      studies that systematically characterize DNA sequence variation in the immediate
      area of D19S884 are required to identify the PCOS susceptibility variant.

PMID- 16091491
TI  - Impact of carbohydrate-rich meals on plasma epinephrine levels: dysregulation
      with aging.
AB  - CONTEXT: Plasma norepinephrine (NE) and epinephrine (E) levels are indicators of
      peripheral sympathetic and adrenomedullary activities, respectively. The
      sympathoadrenomedullary system is involved in the metabolic response to
      carbohydrate intake and is affected by aging; however, the relationship between
      glucose metabolism and adrenomedullary activity in older adults remains poorly
      defined. OBJECTIVE: The objective of this study was to examine the changes in the
      impact of carbohydrate-rich meals on circulating catecholamines with aging.
      DESIGN: After iv glucose tolerance testing and 1 d of habituation, blood samples
      were collected every 10-30 min for 24 h. Daytime hours were spent at bed rest.
      Sleep was scheduled between 2300 and 0700 h with polygraphic monitoring. SETTING:
      The study was performed at a general clinical research center. PARTICIPANTS: Nine
      young (age, 20-28 yr) and eight older (age, 50-69 yr) healthy men participated in
      this study. INTERVENTION: Identical mixed meals (62% carbohydrate) were given at
      0900, 1400, and 1900 h. MAIN OUTCOME MEASURES: The main outcome measures were 24
      h plasma E and NE measurements. RESULTS: The profiles of E and NE were
      characterized by clear day-night differences, which were preserved in the older
      group. Young subjects showed a clear dissociation between postprandial
      adrenomedullary and sympathetic activities characterized by a rapid decline in
      plasma E and increased NE levels. There was an overall increase in NE levels and
      markedly dampened postprandial variation in plasma E in the older men.
      CONCLUSIONS: In young adults, postprandial E levels follow a biphasic pattern
      that is inversely related to that of glucose and insulin. Aging is associated
      with a dysregulation of this response.

PMID- 16091492
TI  - Aggregation of high-normal thyroid-stimulating hormone in hypertensive families.
AB  - BACKGROUND: Studies suggest that there are genetic variants that influence both
      blood pressure regulation and serum TSH levels. We investigated whether high
      normal TSH values aggregate in hypertensive families. The influence of
      hypertension family history on serum TSH levels in healthy normotensive
      individuals was also examined. METHODS: All subjects were euthyroid (TSH, 0.5-5.0
      mIU/liter). The study subjects were 333 hypertensives, including 229 members of
      multiple sibling families. The subjects had blood samples for serum TSH
      determination drawn in the morning after overnight bed rest. High-normal TSH was
      defined as values above 2.0 mIU/liter and equal to or less than 5.0 mIU/liter.
      Thirty-one healthy normotensives provided information about their family history
      of hypertension by telephone. RESULTS: The concordance for high-normal TSH values
      among hypertensive, multiple sibling families was greater than expected by chance
      (P = 0.009). There were nearly twice as many families concordant for high-normal
      TSH status as expected (13.2% vs. 7.0%), whereas the observed proportion
      concordant for normal TSH status was similar to that expected (58.3% vs. 54.1%).
      Family membership explained a significant proportion of variance in TSH status (P
      = 0.038). Healthy normotensives with a family history of hypertension had
      significantly higher TSH values (2.2 +/- 1.2 mIU/liter) than those with a
      negative family history of hypertension (TSH 1.3 +/- 0.7 mIU/liter) independent
      of other characteristics (P = 0.025). CONCLUSIONS: There is familial aggregation
      of high-normal TSH values in hypertensive families, and a hypertension family
      history influences serum TSH levels in healthy individuals. These findings are
      consistent with the existence of genetic variants affecting both blood pressure
      regulation and serum TSH levels.

PMID- 16091493
TI  - A unique role of monocyte chemoattractant protein 1 among chemokines in adipose
      tissue of obese subjects.
AB  - CONTEXT: Low-grade inflammation in adipose tissue may contribute to insulin
      resistance in obesity. However, the roles of individual inflammatory mediators in
      adipose tissue are poorly understood. OBJECTIVES: The objective of this study was
      to determine which inflammation markers are most overexpressed at the gene level
      in adipose tissue in human obesity and how this relates to corresponding protein
      secretion. DESIGN: We examined gene expression profiles in 17 lean and 20 obese
      subjects. The secretory pattern of relevant corresponding proteins was examined
      in human s.c. adipose tissue or isolated fat cells in vitro and in vivo in
      several obese or lean cohorts. RESULTS: In ranking gene expression, defined
      pathways associated with obesity and immune and defense responses scored high.
      Among seven markedly overexpressed chemokines, only monocyte chemoattractant
      protein 1 (MCP1) was released from adipose tissue and isolated fat cells in
      vitro. In obesity, the secretion and expression of MCP1 in adipose tissue pieces
      were more than 6- and 2-fold increased, respectively, but there was no change in
      circulating MCP1 levels. There was no net release of MCP1, but there was a net
      release of leptin, in vivo from adipose tissue into the circulation. CONCLUSIONS:
      Obesity is associated with the increased expression of several chemokine genes in
      adipose tissue. However, only MCP1 is secreted into the extracellular space,
      where it primarily acts as a local factor, because little or no spillover into
      the circulation occurs. MCP1 influences the function of adipocytes, is a
      recruitment factor for macrophages, and may be a crucial link among chemokines
      between adipose tissue inflammation and insulin resistance.

PMID- 16091494
TI  - Leptin and adiponectin responses in overweight inactive elderly following
      resistance training and detraining are intensity related.
AB  - CONTEXT: Adiponectin and leptin are closely related to weight control and energy
      balance, whereas exercise affects elderly metabolic regulation and functional
      capacity. OBJECTIVE: The objective of this study was to investigate leptin and
      adiponectin responses in elderly males after exercise training and detraining.
      DESIGN: The study design was a 1-yr randomized controlled trial. SETTING: The
      study was performed at the Laboratory of Physical Education and Sport Science
      Department. PARTICIPANTS: Fifty inactive men [age, 65-78 yr; body mass index
      (BMI), 28.7-30.2 kg/m2] were recruited from a volunteer database by word of mouth
      and fliers sent to medical practitioners, physiotherapists, and nursing homes in
      the local community. INTERVENTION(S): Participants were randomly assigned to a
      control (n = 10), low-intensity (n = 14), moderate-intensity (n = 12), or high
      intensity training (HI; n = 14) group. Resistance training (6 months, 3 d/wk, 10
      exercises/three sets) was followed by 6 months of detraining. MAIN OUTCOME
      MEASURE(S): Strength, exercise energy cost, skinfold sum, body weight, maximal
      oxygen consumption, resting metabolic rate (RMR), and plasma leptin and
      adiponectin were determined at baseline and after training and detraining.
      RESULTS: Strength, maximal oxygen consumption, RMR, and exercise energy cost
      increased (P < 0.05) after training in an intensity-dependent manner. Skinfold
      sum and BMI were reduced by resistance training (P < 0.05), with HI being more
      effective (P < 0.05) than moderate-intensity/low-intensity training. Leptin was
      diminished (P < 0.05) by all treatments, whereas adiponectin increased (P < 0.05)
      only in HI. Detraining maintained training-induced changes only in HI. The
      percent leptin decrease was associated (P < 0.05) with the percent BMI decrease
      and the percent RMR increase, whereas the percent adiponectin increase was
      associated (P < 0.05) with the percent BMI decrease. CONCLUSIONS: Resistance
      training and detraining may alter leptin and adiponectin responses in an
      intensity-dependent manner. Leptin and adiponectin changes were strongly
      associated with RMR and anthropometric changes.

PMID- 16091495
TI  - Glucocorticoid sensitivity in young healthy individuals: in vitro and in vivo
      studies.
AB  - CONTEXT: Interindividual variation and tissue specificity of glucocorticoid (GC)
      sensitivity may occur in healthy subjects. OBJECTIVE AND PARTICIPANTS: The
      objective of this study was to evaluate the GC sensitivity in 40 healthy young
      subjects (21 women and 19 men; 22-42 yr old). DESIGN: We measured salivary and
      plasma cortisol levels before and after the administration of 0.25, 0.5, and 1 mg
      dexamethasone (DEX), given at 2300 h. We also evaluated the pattern of DEX
      mediated inhibition of concanavalin A-stimulated peripheral blood mononuclear
      cell proliferation using different DEX doses, the number of binding sites, and
      the affinity of the GC receptor (Kd). RESULTS: The increasing DEX doses resulted
      in a dose-dependent decrease in cortisol levels. The majority of the subjects
      (70%) suppressed cortisol with DEX doses lower than 0.5 mg, and two did not
      suppress even with 1 mg DEX. The binding capacity was 4.1 +/- 0.3 fmol/mg
      protein, and the Kd was 8.1 +/- 1.3 nm. Four individuals presented with elevated
      Kd. Peripheral blood mononuclear cell proliferation was inhibited by DEX in a
      dose-dependent pattern. The median IC50 value was 7.1 x 10(-7) mol/liter. We
      found 77.5% (31 of 40) concordance among all three tests; 29 subjects showed all
      parameters between the 10th and 90th percentiles (P10-P90), one above P90, and
      one below P10. These two subjects could be classified as more GC resistant or
      sensitive, respectively. No concordance between in vivo and in vitro tests in two
      subjects suggested a tissue-specific sensitivity. CONCLUSIONS: This is the first
      report that, taking advantage of three bioassays performed on the same subject,
      demonstrated a considerable interindividual variability and tissue-specific GC
      sensitivity in a young healthy population.

PMID- 16091496
TI  - Effects of short-term experimental insulin resistance and family history of
      diabetes on pancreatic beta-cell function in nondiabetic individuals.
AB  - CONTEXT: Normal glucose homeostasis is maintained despite reductions in insulin
      sensitivity by increasing insulin secretion. This ability to compensate for
      reduced insulin sensitivity is highly heritable, but the mechanisms for this
      compensation or its failure in type 2 diabetes (T2DM) are unknown. OBJECTIVE: The
      objective of this study was to test whether individuals with a family history of
      T2DM have a fixed decrease in beta-cell mass or function that would be revealed
      as an impaired insulin secretory response to short-term insulin resistance.
      DESIGN: Glucose tolerance, insulin sensitivity (S(I)), and insulin response to
      i.v. glucose (AIR(G)) were compared in nondiabetic individuals with and without a
      family history of diabetes before and after nicotinic acid (NA) treatment.
      SETTING: This study was performed at the Ambulatory General Clinical Research
      Center. SUBJECTS: Healthy, nonobese, nondiabetic individuals with or without a
      family history of T2DM were studied. INTERVENTIONS: Oral NA was given, with a
      final dose of 2 g/d, for at least 7 d. MAIN OUTCOME MEASURE: The main outcome
      measure was the disposition index (insulin sensitivity x insulin response) in
      response to NA. RESULTS: Postchallenge plasma glucose levels rose during NA
      therapy regardless of family history. Neither group adequately increased their
      AIR(G) to maintain the disposition index. Family members did not differ from
      controls at baseline or after NA treatment for any outcome measure, but only 28
      of 52 subjects experienced a 25% or greater fall in S(I) with NA treatment.
      CONCLUSIONS: Short-term beta-cell compensation to NA-induced insulin resistance
      was incomplete and did not differ by genetic predisposition. A genetic defect
      controlling beta-cell growth in response to chronic insulin resistance better
      explains differences in the ability to compensate for insulin resistance than an
      inherited, fixed defect in beta-cell mass.

PMID- 16091497
TI  - Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times
      in patients with medullary thyroid carcinoma.
AB  - CONTEXT: After unsuccessful surgery, medullary thyroid carcinoma (MTC) may be
      fatal or remain stable for decades, and precise survival predictors are needed.
      OBJECTIVE: This study assesses the prognostic value of calcitonin and
      carcinoembryonic antigen (CEA) doubling-times (DT). DESIGN: This is a
      retrospective study on 65 MTC patients from 2.9-29.5 yr after surgery. SETTING:
      Data registered in the database of the French Neuroendocrine Tumor Group were
      analyzed anonymously. PATIENTS: All patients had abnormal calcitonin levels after
      total thyroidectomy and bilateral lymph node dissection. INTERVENTION: Calcitonin
      and CEA serum levels were measured during routine disease follow-up. MAIN OUTCOME
      MEASURE: To assess DT as prognostic factors, a patient population was extracted
      from the database. RESULTS: When calcitonin DT was less than 6 months, 5- and 10
      yr survivals were three of 12 (25%) and one of 12 (8%), respectively; when
      between 6 months and 2 yr, 5- and 10-yr survivals were 11 of 12 (92%) and three
      of eight (37%), whereas all 41 patients with calcitonin DT greater than 2 yr were
      alive at the end of the study. Tumor-Node-Metastasis (TNM) stage, European
      Organization for Research and Treatment of Cancer (EORTC) score, and calcitonin
      DT were significant predictors of survival by univariate analysis, but only
      calcitonin DT remained an independent predictor of survival by multivariate
      analysis (P = 0.002) with a proportion of variance explained (PVE) of 37.4%.
      Calcitonin DT was a better predictor than CEA (PVE 63.3% and 47.0%,
      respectively). Calcitonin DT calculated using only the first four measurements
      was also an independent predictor of survival (P < 0.000001; PVE 40.4%).
      CONCLUSION: Calcitonin DT may be superior to initial clinical staging and among
      the most powerful prognostic indicators in MTC.

PMID- 16091498
TI  - Spontaneous diurnal thyrotropin secretion is enhanced in proportion to
      circulating leptin in obese premenopausal women.
AB  - CONTEXT: Recent evidence implicates leptin as an important modulator of thyroid
      axis activity. OBJECTIVE: The objective of this study was to study spontaneous 24
      h TSH secretion and 24-h circulating leptin concentrations in obese and lean
      women. DESIGN: This was a prospective parallel study (2004). SETTING: This study
      was conducted at the Clinical Research Center (Leiden University Medical Center,
      Leiden, The Netherlands). PARTICIPANTS: Twelve healthy obese premenopausal women
      (body mass index, 33.2 +/- 0.9 kg/m2) and 11 lean controls (body mass index, 21.4
      +/- 0.5 kg/m2) were studied in the follicular phase of their menstrual cycle.
      INTERVENTION(S): There were no interventions in this study. MAIN OUTCOME
      MEASURE(S): Spontaneous 24-h TSH concentrations (10-min time intervals) and
      secretion were calculated using waveform-independent deconvolution technique
      (pulse). Twenty-four-hour circulating leptin concentrations (20-min time
      intervals) were measured. RESULTS: Mean TSH concentration (obese, 1.9 +/- 0.2 vs.
      lean, 1.1 +/- 0.1 mU/liter; P = 0.009) and secretion rate (obese, 43.4 +/- 5.5
      vs. lean, 26.1 +/- 2.2 mU/liter distribution volume.24 h; P = 0.011) were
      substantially enhanced in obesity, whereas the fasting free T4 (fT4)
      concentrations were similar (fT4 in obese, 15.4 +/- 1.5 vs. in lean, 16.4 +/- 1.5
      pmol/liter; P = 0.147). TSH secretion was positively related to 24-h leptin
      concentrations (r2= 0.31; P = 0.007). CONCLUSIONS: TSH release is enhanced in the
      face of normal plasma fT4 concentrations in obese premenopausal women, and
      hyperleptinemia may well be involved in this neuroendocrine alteration.

PMID- 16091499
TI  - Polymorphisms in the initiators of RET (rearranged during transfection) signaling
      pathway and susceptibility to sporadic medullary thyroid carcinoma.
AB  - CONTEXT: Medullary thyroid carcinoma (MTC) is a characteristic tumor occurring in
      individuals with multiple endocrine neoplasia type 2 who carry germ-line
      mutations in RET (rearranged during transfection). However, most MTC occur in
      individuals without a family history. OBJECTIVES: The objective of this study was
      to explore the possibility that susceptibility in these cases results from low
      penetrance alleles of RET, its coreceptors, and ligands. DESIGN: We carried out
      an association study in 135 sporadic MTC (sMTC) patients and 533 controls from
      the United Kingdom population. RESULTS AND CONCLUSIONS: We analyzed 33
      polymorphisms in all nine genes involved in the glial cell line-derived
      neurotropic factor receptor-alpha (GFRalpha)-RET complex. This is the first
      association study in which all genes involved in this complex have been
      investigated for susceptibility to sMTC. We did not find any association between
      single nucleotide polymorphisms in the exonic regions of the GFRalpha2,
      GFRalpha3, GFRalpha4, glial cell line-derived neurotropic factor, neurturin, or
      persephin genes and risk of developing sMTC. We found a strong association
      between the disease and specific haplotypes of RET. We not only confirmed the
      previously described association with G691S and S904S (for heterozygotes: odds
      ratio, 1.85; range, 1.22-2.82; P = 0.004), but we found a novel protective effect
      associated with a specific haplotype (odds ratio, 0.39; range, 0.21-0.72; P =
      0.005) revealing the existence of different genetic variants in the RET oncogene
      that either increase or decrease risk of sMTC.

PMID- 16091500
TI  - Deconvolution analysis of rapid insulin pulses before and after six weeks of
      continuous subcutaneous administration of glucagon-like peptide-1 in elderly
      patients with type 2 diabetes.
AB  - CONTEXT: Insulin is secreted in a pulsatile fashion with measurable orderliness
      (low entropy). Normal aging and diabetes in middle-aged patients is characterized
      by alterations in pulsatile insulin release. OBJECTIVES: We undertook the current
      studies to determine whether disruptions in pulsatile insulin release also
      accompany diabetes in the elderly. DESIGN: Two studies were performed. In the
      first study, insulin values were sampled every minute for 1 h under fasting
      conditions. In the second study, subjects underwent a 2-h hyperglycemic glucose
      clamp (glucose 5.4 mm above basal). From 60-120 min, insulin was sampled every 1
      min. Secretory pulse analysis was conducted using a multiparameter deconvolution
      technique. SETTING: The study was conducted in a general clinical research center
      and during outpatient visits. PATIENTS: Volunteers were healthy young [n = 10;
      body mass index (BMI), 23 +/- 1 kg/m2; age, 23 +/- 1 yr] and elderly (n = 10;
      BMI, 24 +/- 1 kg/m2; age, 78 +/- 2 yr) volunteers and elderly patients with
      diabetes (n = 8; BMI, 28 +/- 1 kg/m2; age, 73 +/- 2 yr). INTERVENTION: Five of
      the older patients with type 2 diabetes (BMI, 29 +/- 1 kg/m2; age, 72 +/- 2 yr)
      were treated with continuous sc glucagon-like peptide-1 (GLP-1) (7-36) amide
      infusion for 6 wk, and a second 2-h hyperglycemic clamp was performed. MAIN
      OUTCOME MEASURES: Insulin burst mass, pulsatile insulin secretion, and entropy
      were measured. RESULTS: Under fasting conditions, elderly patients with diabetes
      had a reduction in insulin burst mass (P < 0.05) that was similar to normal
      elderly. During hyperglycemia, elderly patients with diabetes had an even greater
      impairment in insulin burst mass (P < 0.05) and basal (P < 0.05) and pulsatile
      insulin secretion (P < 0.05) than normal elderly. Approximate entropy, a measure
      of irregularity of insulin release, was increased to a greater extent in older
      diabetes patients than normal elderly, signifying loss of orderliness of insulin
      secretion (P < 0.05). In response to treatment with GLP-1, insulin burst mass (P
      < 0.05) and pulsatile insulin secretion (P < 0.05) improved significantly in
      elderly patients with diabetes. CONCLUSIONS: We conclude that alterations in
      pulsatile insulin release can be improved in elderly patients with diabetes by
      the administration of sc GLP-1.

PMID- 16091501
TI  - MRI and the evaluation of the blood-spinal cord barrier following injury.

PMID- 16091502
TI  - Vertebroplasty and the randomized study: where science and ethics collide.

PMID- 16091503
TI  - Evaluation of the pathologic characteristics of excitotoxic spinal cord injury
      with MR imaging.
AB  - BACKGROUND AND PURPOSE: Although high-resolution MR imaging is a valuable
      diagnostic tool, in vivo MR imaging has not yet been compared with in vitro MR
      imaging and histologic techniques following experimental spinal cord injury
      (SCI). The goal of the present study was to evaluate the feasibility of using in
      vivo MR imaging, in vitro MR imaging, and histologic techniques to study
      pathologic changes associated with excitotoxic SCI at a single time point. These
      results are important for future research using in vivo MR imaging to study the
      temporal profile of pathologic changes following SCI. METHODS: Rats received
      intraspinal injections of quisqualic acid at the T12-L2 spinal level. In vivo T1-
      and T2-weighted and dynamic contrast-enhanced MR images were collected 17-24 days
      postinjury. Once completed, spinal cords were removed and in vitro MR microscopy
      and histologic assessment were performed. MR images were collected using 4.7-T
      (in vivo) and 14.1-T magnets (in vitro). RESULTS: Pathologic changes--including
      hemorrhage, neuronal loss, cavities, and central canal expansion--were visible in
      T2-weighted in vivo MR images. Evaluation of the blood-spinal cord barrier after
      injury with contrast agent enhancement showed no disruption at the time points
      evaluated. In vitro MR images and histologic evaluation confirmed pathologic
      details observed in vivo. CONCLUSION: Results show that high-resolution in vivo
      MR imaging has the potential to be used in studying the progression of pathologic
      changes at multiple time points following SCI. This strategy may provide a way of
      studying structure-function relationships between therapeutic interventions and
      different pathologic characteristics of the injured spinal cord.

PMID- 16091504
TI  - Prospective analysis of clinical outcomes after percutaneous vertebroplasty for
      painful osteoporotic vertebral body fractures.
AB  - BACKGROUND AND PURPOSE: Previous studies have retrospectively reported the
      positive effects of percutaneous vertebroplasty. The purpose of our study was to
      evaluate prospectively the effects of vertebroplasty on mobility, analgesic use,
      pain, and SF-36 (short-form 36-item) scales for patients with painful vertebral
      compression fractures that are refractory to medical therapy. METHODS: We
      prospectively followed 167 patients who received 207 vertebroplasty treatment
      sessions for stabilization of 264 symptomatic vertebral compression fractures
      between August 1999 and January 2003. The average age of patients was 74.6 years
      (SD = 12.2 years), and 76% were women. Pre- and postprocedural measurements of
      pain, mobility, analgesic use, and SF-36 scales were compared at 1 month after
      the procedure and between 6 months and 3 years after the procedure with the SF-36
      scales. RESULTS: Respective pre- and post-treatment pain scores were 8.71 (SE =
      0.1) and 2.77 (SE = 0.18; P < .00001). Respective pre- and post-treatment
      analgesic use scores were 2.93 (SE = 0.9) and 1.64 (SE = 0.09; P < .00001).
      Respective pre- and post-treatment activity levels were 2.66 (SE = 0.1) and 1.64
      (SE = 0.11; P < .00001). There was a statistically significant improvement on
      nine of 10 SF-36 scales (P < .001) after 1 month and on eight of 10 SF-36 scales
      (P < .02) at long-term follow-up. CONCLUSION: Percutaneous vertebroplasty offers
      statistically significant benefits in decreasing pain, decreasing use of
      analgesics, and increasing mobility in appropriately selected patients.
      Percutaneous vertebroplasty also offers a statistically significant benefit in
      most SF-36 scales at both short- and long-term follow-up.

PMID- 16091505
TI  - Vertebroplasty in the inpatient population.
AB  - BACKGROUND AND PURPOSE: Vertebroplasty is frequently offered to patients
      hospitalized for refractory pain due to vertebral fractures, because it is
      assumed that the procedure will facilitate resolution of pain and a rapid
      hospital discharge. We report our experience with inpatient vertebroplasty, with
      attention to rapidity of discharge and relevant clinical parameters. METHODS: We
      retrospectively reviewed the duration of hospitalization in patients admitted
      with primary diagnoses of back pain or vertebral fracture who were treated with
      vertebroplasty. We cataloged outcomes in the form of verbal pain scales (graded 0
      10), in-hospital medication use (graded 0-6), and posthospitalization medication
      use. Outcomes were assessed at baseline and at 1 week, 1 month, 6 months, 1 year,
      and 2 years postvertebroplasty. RESULTS: We identified 66 such patients who had a
      median total hospital stay of 6.0 days (range, 1-26 days). Median length of stay
      before and after vertebroplasty were 4.0 (range, 1-24 days) and 1.5 days (range,
      0-7 days), respectively. Ten (15%) patients were discharged the day of
      vertebroplasty. By days 2 and 3, 33 (50%) and 48 (72.7%) of the 66 patients had
      been discharged. Patients who received vertebroplasty earlier in the course of
      hospitalization demonstrated greater decreases in medication strength by
      discharge (P = .045). There was significant improvement in all outcome measures
      by 1 week, with continued improvement at 1 and 6 months. CONCLUSION: This study
      confirms that vertebroplasty facilitates a rapid hospital discharge as well as
      long-term improvement in patients admitted for refractory pain. Vertebroplasty
      administered earlier in hospitalization also leads to greater decreases in
      analgesic requirements.

PMID- 16091506
TI  - Vacuum clefts of the vertebral bodies.
AB  - BACKGROUND AND PURPOSE: The appearance of vacuum clefts (VCs) of the vertebral
      bodies has frequently been considered pathognomonic for avascular necrosis. Until
      recently, this was considered to be a rare finding that might indicate excessive
      motion at the fracture site. Our aim in this retrospective study was to determine
      the occurrence and location of these clefts in patients with osteoporotic
      vertebral fractures and evaluate the risk factors involved for developing these
      clefts in such patients. METHODS: The records of 66 patients with 101 painful
      osteoporotic vertebral fractures who were treated by vertebroplasty in our
      department were reviewed. All the fractures with VCs were collected. Age, sex,
      degree of deformity, and extent of degenerative changes in the adjacent disk
      space were compared with those found in the patients without clefts. RESULTS: VCs
      were found in 26 fractured vertebrae of 26 patients. They were significantly more
      common in elderly men who had deformed fractures located at the thoracolumbar
      junction, when compared with fractures without clefts, especially when
      degenerative changes were observed in the adjacent disk space. CONCLUSION: This
      study suggests that VCs, which have long been considered pathognomonic for
      avascular necrosis (Kummell disease), are not rare and most probably represent
      fracture nonunion. Elderly patients who have deformed fractures at the
      thoracolumbar area have a higher risk for developing clefts, mainly when there is
      degeneration of the adjacent disk space.

PMID- 16091507
TI  - Percutaneous vertebroplasty for metastatic involvement of the axis.
AB  - BACKGROUND AND PURPOSE: Percutaneous vertebroplasty in the upper cervical spine
      is a challenging procedure, and little is known about its therapeutic outcome.
      The purpose of this study was to assess the risks and benefits of percutaneous
      vertebroplasty for metastatic involvement of the axis. METHODS: From January 1994
      to August 2004, 12 patients (mean age, 52.3 years) underwent percutaneous
      vertebroplasty via an anterolateral approach using fluoroscopic guidance for
      metastatic lesions involving the C2 vertebral body; pain intensity was scored on
      a scale ranging from 0.0 (no pain) to 10.0 (maximum pain intensity). Eight
      patients (66.7%) were followed up (mean, 6.9 months); 5 of them had percutaneous
      vertebroplasty indicated for pain control and spine stabilization and 3, for
      spine stabilization only. RESULTS: The mean volume of cement injected was 2.9 +/-
      0.7 mL (range, 2.0-4.0 mL) with a mean vertebral filling of 60.7 +/- 14.6%
      (range, 25-80%). Cement leakage was detected in 7 treated vertebrae (58.3%). Pain
      improvement was achieved in 4/5 patients (80%). Spine stability was observed in 7
      patients (87.5%), but 1 patient (12.5%) presented with a secondary spine
      deformity in association with partial vertebral filling. Two postprocedural
      clinical manifestations (16.7%) were observed: 1 patient (8.3%) had a transient
      occipital neuralgia and another (8.3%) had an ischemic stroke. Mortality and
      morbidity rates at mean follow-up were 0.0% and 12.5% (1 patient), respectively.
      CONCLUSION: Percutaneous vertebroplasty of C2 metastases by an antero-lateral
      approach is an effective option in the treatment strategy of patients with
      metastases to C2. Nevertheless, it is a challenging procedure and may carry
      regional and even intracranial risks due to the proximity to the vertebral
      artery.

PMID- 16091508
TI  - Spinal cord schistosomiasis: MR imaging appearance with surgical and pathologic
      correlation.
AB  - BACKGROUND AND PURPOSE: Spinal cord involvement is a rare manifestation of
      schistosomiasis. We describe the MR imaging findings of spinal cord
      schistosomiasis in correlation with surgery and pathology. METHODS: We report
      eight cases of spinal cord schistosomiasis. All patients were men (mean age, 16.7
      years) with neurologic manifestations who had been referred for spinal MR
      imaging. In all cases, spinal masses were surgically removed. MR imaging findings
      were correlated with surgery and pathology. RESULTS: MR imaging showed moderate
      expansion of the distal spinal cord in all cases. Abnormalities were isointense
      to cord in T1 and patchy hyperintense in T2-weighted spin-echo images (n = 8).
      Three forms of contrast enhancement were recognized: (1) intramedullary nodular
      (n = 8); (2) peripheral (n = 8); and (3) linear radicular (n = 4). Total gross
      surgical removal of masses by using the Cavitron ultrasonic surgical aspirator
      was possible in six cases. Diagnosis was established by identification of ova in
      histopathologic studies: Schistosoma mansoni (n = 3), S. hematobium (n = 1), and
      uncertain species (n = 4). Intramedullary nodular enhancement was correlated to
      multiple schistosomiasis microtubercles. Peripheral enhancing lesions correlated
      to thickened leptomeninges infested by chronic granulomatous inflammatory cells
      and schistosoma eggs. Linear radicular enhancement correlated with thickened
      resected nervous roots infested by granulomatous cells and schistosoma eggs.
      CONCLUSION: Multinodular intramedullary contrast enhancement of the distal cord
      enabled correct presumptive preoperative MR imaging diagnosis of spinal
      schistosomiasis in three cases. Accurate diagnosis, through recognition of its MR
      imaging appearance, allows early treatment and better prognosis of spinal cord
      schistosomiasis.

PMID- 16091509
TI  - Transient traumatic spinal venous hypertensive myelopathy.
AB  - We present a case of a reversible spinal venous hypertensive myelopathy that
      occurred following a traumatic mediastinal hematoma. The mediastinal hematoma
      caused compression of the brachiocephalic vein, resulting in elevation of the
      venous pressures that ultimately resulted in dilation of the epidural venous
      plexus and spinal cord edema. The secondary neurologic deficits were the
      culmination of venous outflow obstruction at the level of the spinal cord that
      resolved on the resolution of the mediastinal hematoma.

PMID- 16091510
TI  - Disruption of cerebellar development: potential complication of extreme
      prematurity.
AB  - BACKGROUND AND PURPOSE: Infants with very low birth weight are at high risk for
      cerebral lesions. Although supratentorial brain damage is a common radiologic
      finding, posterior fossa pathologies are rare. We studied the morphology of
      cerebellar involvement in a large series of 28 premature infants born before the
      30th week of gestation to define typical patterns and identify possible risk
      factors for this pathology. METHODS: Cranial sonograms were obtained in the early
      neonatal period. MR imaging was performed between the 2nd month and the 6th year
      of life. Morphologic patterns of cerebellar involvement were evaluated. RESULTS:
      Three morphologic patterns of cerebellar involvement were recognized: (1)
      symmetric volume reduction of the cerebellar hemispheres, which were floating
      immediately beneath the tentorium, and a small vermis with preserved shape; (2)
      symmetrical reduction in hemispheric volume with an enlarged, balloon-shaped
      fourth ventricle and a small, deformed vermis; and (3) normal overall cerebellar
      shape with extensive reduction of its dimensions. A small brain stem with
      flattened anterior curvature of the pons and loss of supratentorial white matter
      was present in all patients. CONCLUSION: Symmetric cerebellar volume reduction
      was found as a consequence of extreme prematurity. Selective vulnerability of the
      developing cerebellum in the window of 24-30 weeks of gestation, combined with
      several additive perinatal risk factors (eg, hemosiderin deposits) seems to lead
      to destruction of immature structures and developmental arrest. Therefore, the
      resulting condition is the consequence of disrupted cerebellar development.

PMID- 16091511
TI  - Thiamine deficiency in infants: MR findings in the brain.
AB  - BACKGROUND AND PURPOSE: Thiamine deficiency is extremely rare in infants in
      developed countries. To our knowledge, its MR findings in the brain have not been
      reported. The purpose of this study was to investigate the brain MR findings in
      infants with encephalopathy due to thiamine deficiency. METHODS: The study group
      included six infants aged 2-10 months with encephalopathy who had been fed with
      solely soy-based formula devoid of thiamine from birth. All underwent MR
      evaluation at admission and follow-up (total of 14 examinations). In one patient,
      MR spectroscopy (MRS) was performed. RESULTS: In five patients T2-weighted, fluid
      attenuated inversion recovery, or proton-attenuated sequences showed bilateral
      and symmetric hyperintensity in the periaqueductal area, basal ganglia and
      thalami. Five had lesions in the mammillary bodies, and three, in the brain stem.
      In all six patients, the frontal region (cortex and white matter) was clearly
      involved. At presentation, MRS of the periaqueductal area showed a lactate
      doublet. On long-term follow-up, three of four patients had severe frontal
      damage; in two, this occurred as part of diffuse parenchymal loss, and in one, it
      was accompanied by atrophy of the basal ganglia and thalami. CONCLUSION: Thiamine
      deficiency in infants is characterized by involvement of the frontal lobes and
      basal ganglia, in addition to the lesions in the periaqueductal region, thalami,
      and the mammillary bodies described in adults. MRS demonstrates a characteristic
      lactate peak.

PMID- 16091512
TI  - Predominant cerebellar volume loss as a neuroradiologic feature of pediatric
      respiratory chain defects.
AB  - BACKGROUND AND PURPOSE: Predominant cerebellar involvement has not been
      previously reported as a common neuroradiologic feature in pediatric
      mitochondrial cytopathies. Here we report the neuroradiologic findings of
      predominant cerebellar volume loss in children with various mitochondrial
      disorders. METHODS: A retrospective analysis of the medical records of 400
      consecutive patients referred for evaluation of mitochondrial encephalomyopathies
      was performed. In 113 cases, definite diagnosis of mitochondrial disease was
      based on the modified adult criteria that include clinical, histologic,
      biochemical, functional, molecular, and metabolic parameters. RESULTS:
      Predominant cerebellar volume loss with progressive cerebellar atrophy and, less
      often, cerebellar hypoplasia were found in a heterogeneous group of patients with
      mitochondrial disease that consisted of four patients with complex I deficiency;
      four patients with multiple respiratory chain deficiencies; two patients with
      combined complex I + III and II + III deficiencies, including one patient with
      partial coenzyme Q10 deficiency; three patients with complex II deficiency; two
      patients with complex IV deficiency; one patient with mitochondrial
      neurogastrointestinal encephalomyopathy; and two patients with mitochondrial
      encephalomyopathy, lactic acidosis, and strokes. CONCLUSION: Our retrospective
      study shows that isolated or predominant cerebellar involvement can be found in
      various respiratory chain defects or mitochondrial disorders expanding the
      classical neuroradiologic findings observed in mitochondrial encephalomyopathies.
      The diagnostic workup in patients with neuromuscular features whose brain MR
      imaging exhibits cerebellar volume loss should include the evaluation for
      mitochondrial encephalomyopathies.

PMID- 16091513
TI  - MR imaging-based volumetry in patients with early-treated phenylketonuria.
AB  - BACKGROUND AND PURPOSE: Our purpose was to specify the most severely affected
      brain structures in early treated phenylketonuria regarding volume loss and
      establish possible correlations between volume loss and plasma levels of
      phenylalanine (Phe). METHODS: In 31 patients with early treated phenylketonuria
      and in 27 healthy volunteers, we acquired volumetric MR imaging data. Serum Phe
      concentrations at different times were measured as well. Semiautomatic volumetric
      postprocessing of the cerebellum, cerebrum (supratentorial brain tissue),
      hippocampus, intracranial volume, lateral ventricles, nucleus caudatus, nucleus
      lentiformis, pons, and thalamus, as well as the two-dimensional extension of the
      corpus callosum, was performed using the software BRAINS2. For each separate
      brain structure, the relative differences between the normal and the
      phenylketonuria group (delta(rel)) were calculated. RESULTS: The cerebrum, corpus
      callosum, hippocampus, intracranial volume, and pons were significantly smaller
      in patients with phenylketonuria than in healthy patients. The volume of the
      lateral ventricles was significantly larger in patients with phenylketonuria than
      in healthy ones. The most severely affected structures were the pons (delta(rel)
      = 16%), hippocampus (delta(rel) = 14.5%), cerebrum (delta(rel) = 13%), and corpus
      callosum (delta(rel) = 10%). No significant differences were found for the basal
      ganglia, cerebellum, and thalamus. There were no significant correlations found
      between the volume of any of the different brain structures and the metabolic
      parameters. CONCLUSION: The most severely affected brain structures in early
      treated patients with phenylketonuria regarding volume loss are the cerebrum,
      corpus callosum, hippocampus, and pons.

PMID- 16091514
TI  - Diffusion-weighted MR imaging of early methotrexate-related neurotoxicity in
      children.
AB  - BACKGROUND AND PURPOSE: Methotrexate is a major cause of treatment-related acute
      neurotoxicity in children with hematologic malignancies. The purpose of this
      study was to investigate whether diffusion-weighted MR imaging (DWI) detects
      acute methotrexate white matter neurotoxicity in this patient population.
      METHODS: Six children-three female and three male-with hematologic malignancies
      were studied at time of onset of neurologic dysfunction during the delayed
      intensification or consolidation phase of therapy, when intensive intrathecal
      methotrexate is given. MR imaging including DWI was performed on 1.5 T MR
      scanners. RESULTS: DWI demonstrated abnormal restriction of motion of water in
      the centrum semiovale in all six patients. This finding correlated to the acute
      onset of hemiparesis or aphasia. Fluid-attenuated inversion recovery imaging was
      not positive at this time, but it was positive in all five patients in whom
      follow-up imaging was performed. CONCLUSION: Early detection of methotrexate
      white matter injury by DWI has the potential to alert the oncologist to this
      event and provide a technique by which treatment of neurotoxicity can be
      monitored.

PMID- 16091515
TI  - Brain apparent diffusion coefficient decrease during correction of severe
      hypernatremic dehydration.
AB  - We report on the brain diffusion MR imaging findings in a neonate with severe
      hypernatremic dehydration, which resulted in cerebral edema (osmotic edema) and
      in apparent diffusion coefficient decrease, despite a careful and slow
      rehydration. This report provides in vivo insight into nervous cell response to
      osmotic challenge.

PMID- 16091516
TI  - Pediatric central nervous system posttransplant lymphoproliferative disorder.
AB  - Post-transplant lymphoproliferative disorder complicates approximately 1% of all
      renal transplants. The usual site of occurrence is within the abdomen, thorax,
      allograft, or head and neck. Central nervous system involvement is uncommon but,
      when present, occurs in isolation, sparing other organ systems. Few articles in
      the radiology literature have focused on the acute and follow-up central nervous
      system findings of the disease, especially in children. Because the clinical and
      imaging characteristics of central nervous system post-transplant
      lymphoproliferative disorder overlap those of infection and primary central
      nervous system lymphoma and the fact that untreated posttransplant
      lymphoproliferative disorder has a poor prognosis, it is important to maintain a
      high index of suspicion for this disorder so that appropriate treatment can be
      instituted.

PMID- 16091517
TI  - Application of transcranial Doppler sonography in children with acute neurologic
      events due to primary cerebral and West Nile vasculitis.
AB  - We describe the use of serial transcranial Doppler studies to evaluate
      neurovascular disease in three girls presenting with acute stroke due to primary
      cerebral vasculitis (n = 2) and West Nile vasculitis (n = 1). Correlation of
      abnormal findings on transcranial Doppler sonography was compared with those of
      MR angiography and conventional angiography in each child. All three girls had
      left middle cerebral artery infarcts on MR imaging, with an abnormal left middle
      cerebral artery detected by MR angiography, conventional angiography, and
      transcranial Doppler sonography in each child. In all three cases, findings of
      the transcranial Doppler sonography, MR imaging, and catheter angiography were
      concordant.

PMID- 16091518
TI  - Acute and chronic swine rete arteriovenous malformation models: hemodynamics and
      vascular remodeling.
AB  - BACKGROUND AND PURPOSE: An acute and a chronic arteriovenous malformation (AVM)
      model were developed by using the swine rete to study hemodynamics and vascular
      remodeling. The models were also used to study in vivo polymerization kinetics
      and the distribution of various N-butyl 2-cyanoacrylate (NBCA) and Lipiodol
      mixtures. METHODS: In the acute swine AVM model, retrograde flow through the left
      side of the rete was created by the placement of an endovascular shunt through
      the ipsilateral ascending pharyngeal artery. In the chronic model, flow was
      redirected retrograde through the left side of rete and ascending pharyngeal
      artery by creating an arteriovenous fistula between the ipsilateral jugular vein
      and the common carotid artery. After a period of at least 6 months, the entire
      head with the rete was connected to a perfusion loop driven by a peristaltic
      pump. A total of 30 swine were used for both the acute (n = 23) and chronic
      groups (n = 7). Hemodynamic parameters, including the flow and pressure drop
      across the rete, were recorded before NBCA embolization. Image processing was
      used on high-resolution radiographs of the explanted retia to measure the total
      rete length. Measurements of rete vessel calibers were based on histology.
      RESULTS: The pressure gradients across retia were higher in the chronic model
      than in the acute model, but they did not reach the level of statistical
      significance (23.7 +/- 12.0 mm Hg vs 15.4 +/- 1.4 mm Hg). The rete blood outflow
      was significantly higher in the chronic model compared with the acute one (139.9
      +/- 100.3 mL/min vs 32.5 +/- 17.6; P = .03). The rete length in the chronic model
      was significantly higher than in the acute model (593.1 +/- 39.9 vs 401.3 +/-
      65.2 pixel; P < .001). The average vessel diameter of the rete in the chronic
      group was 520 microm and 320 microm in the control animals. CONCLUSION: Increased
      pressure gradients and flow in the chronic swine rete AVM model may be related to
      increased size and decreased impedance. The resulting hemodynamic changes reflect
      a true flow-induced vascular remodeling rather than a simple change related to
      aging and size of the animal.

PMID- 16091519
TI  - Acute and chronic swine rete arteriovenous malformation models: effect of
      ethiodol and glacial acetic acid on penetration, dispersion, and injection force
      of N-butyl 2-cyanoacrylate.
AB  - BACKGROUND AND PURPOSE: Liquid embolic agents are increasingly gaining importance
      in the embolization of cerebral arteriovenous malformations (AVMs). Currently,
      the most commonly used agent is N-butyl 2-cyanoacrylate (NBCA). Various NBCA
      mixtures, arterial hypotension, and Valsalva maneuver (increased positive end
      expiratory pressure) during the injection of the acrylate have been used to
      address hemodynamic and architectural variations of an AVM; however, the precise
      in vivo polymerization, distribution, and kinetics of NBCA mixtures are unknown.
      We investigated the effect of different acrylate/Lipiodol mixtures and the
      addition of glacial acetic acid (GAA) on the penetration, dispersion, and
      injection force of NBCA. METHODS: A swine rete AVM model that has been described
      elsewhere was used for the embolization. In one subgroup of animals, embolization
      was performed immediately after construction of the AVM model. In a second
      subgroup, a chronic AVM model was used. GAA was added to the NBCA mixture to
      decrease the pH value of the solution and prolong the polymerization time. The
      addition of GAA allowed us to reduce the amount of Lipiodol, thereby reducing the
      viscosity of the mixture. A total of 30 swine were used for both the acute (n =
      23) and chronic (n = 7) subgroups. The following mixtures of Lipiodol/NBCA and
      GAA (% vol/%vol + microL) were used for embolization: 80/20 + 0; 50/50 + 0; 50/50
      + 5; 50/50 + 10; and 50/50 + 20. A total of six retia per mixture were used for
      the analysis. Glue injection pressure profiles were recorded in each experiment.
      High-resolution radiographic images obtained from the harvested retia were used
      to correlate the dispersion and depth of glue penetration with the AVM
      hemodynamics. The effect of different amounts of GAA on the glue dispersion and
      depth of penetration of the mixtures was also studied. RESULTS: Using the same
      pressure gradients, less viscous NBCA + GAA mixtures led to a deeper nidal
      penetration. The addition of 20 microL of GAA resulted in a three times higher
      penetration and dispersion of the NBCA mixture that was more homogenous.
      CONCLUSION: The viscosity of the liquid embolic agent used is an important
      limiting factor for an AVM embolization. Reducing the amount of Lipiodol improves
      nidus penetration. Quicker polymerization can be overcome by adding GAA, which
      reduces the pH of the mixture.

PMID- 16091520
TI  - Dural sinus compartment in dural arteriovenous shunts: a new angioarchitectural
      feature allowing superselective transvenous dural sinus occlusion treatment.
AB  - BACKGROUND AND PURPOSE: The dural sinus occlusion has been shown to be effective
      in the treatment of some dural arteriovenous shunts (DAVS). No long-term results
      are available, however, regarding the significance of occlusion of a dural sinus.
      If the disease will stop or if other events will occur later in the remaining
      sinuses are not well known yet. Careful analyses of our cases led us to discover
      that, in some instances, the shunt involves only a single portion or compartment
      of a sinus. In this report, we describe our results in the treatment of these
      lesions: occluding only the involved compartment while preserving patency of the
      remainder of the sinus and the angiographic signals, thus allowing diagnosis of
      the presence of a compartment. METHODS AND RESULTS: From 1996 to October 2002, we
      found 12 cases of DAVS (among 40 news cases of DAVS) with two types of
      compartments--one inside the sinus, which we call "septation" (nine cases), and
      the other outside the sinus, which we call "accessory sinus" (three cases). It
      was possible to occlude completely the lesion superselectively in nine cases. In
      two cases, it was necessary to occlude the entire sinus secondarily, and in one
      case the sinus was occluded because was impossible to catheterize the septation.
      Two cases with recanalization on the control were treated by additional arterial
      and arterial and venous approach. CONCLUSION: It is very important to diagnose
      the presence of a compartment in dural arteriovenous shunts during the diagnostic
      angiography. In most cases, it allows curative treatment of the lesion by
      occluding only the compartment while preserving patency of the remainder of the
      sinus.

PMID- 16091521
TI  - A multicenter study of 705 ruptured intracranial aneurysms treated with Guglielmi
      detachable coils.
AB  - BACKGROUND AND PURPOSE: The long-term durability of Guglielmi detachable coil
      (GDC) embolization of cerebral aneurysms is still unknown. The purpose of this
      study was to evaluate the stability of anatomic occlusion of aneurysms treated
      with GDCs and assess the rate of recanalization and re-treatment. METHODS: A
      multicenter study involving 650 patients with 705 ruptured aneurysms treated with
      GDCs between January 1998 to May 2003 was conducted. During this period, 63% of
      ruptured aneurysms were treated by the endovascular technique. The morbidity and
      mortality associated with this technique, procedural feasibility, acute
      angiographic occlusion results, and long-term angiographic follow-up were
      assessed. RESULTS: Overall technical feasibility of GDC treatment was 96.9%. Upon
      admission, 25% of patients were Hunt and Hess grade IV or V. Acute angiographic
      results in 683 aneurysms demonstrated total occlusion in 496 cases (72.6%),
      subtotal occlusion in 171 cases (25.%), and incomplete occlusion in 16 cases
      (2.4%). All patients were controlled by angiography and MR imaging at 3 months, 1
      year, and subsequent yearly examinations post-treatment. A second treatment was
      performed in 27 cases (recanalization, 4.7%). Long-term follow-up angiograms
      (mean, 36 months) were obtained in 571 aneurysms (95%). Of them, 422 aneurysms
      (73.9%) demonstrated complete occlusion, 148 aneurysms (25.9%) demonstrated
      subtotal occlusion, and only 1 aneurysm was incompletely occluded. Overall
      mortality was 11.4% for all patients, with procedural mortality evaluated at
      1.4%. Overall morbidity was calculated at 8.6%. Only one rebleeding occurred in
      our study, with a second procedure performed without vital consequences for the
      patient. CONCLUSION: Our multicenter study confirms the stability of aneurysm
      embolization with GDC, with only 4.7% of aneurysms requiring re-treatment.

PMID- 16091522
TI  - Endovascular treatment of posterior circulation cerebral aneurysms by using
      Guglielmi detachable coils: a 10-year single-center experience with special
      regard to technical development.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to analyze the immediate
      and long-term angiographic and clinical results of endovascular treatment of
      posterior circulation aneurysms with special regard to technical development.
      MATERIALS: Between 1993 and 2003, 46 patients with 47 aneurysms of the posterior
      circulation were referred to our institution for endovascular treatment. Mean
      angiographic follow-up was 1.7 years. Clinical follow-up was determined at
      hospital discharge and by using a questionnaire for long-term follow-up (mean,
      3.3 years). To analyze technical development, patients treated before (group 1)
      and after (group 2) implementation of 3D Guglielmi detachable coils (3D GDCs) in
      1999 were compared. Multivariate analysis was performed to determine factors
      predictive of clinical and technical outcome. RESULTS: Overall, at initial
      treatment complete occlusion was achieved in 27 (57.4%) aneurysms, a neck remnant
      was present in 16 (34.0%) aneurysms, incomplete occlusion was achieved in 3
      (6.4%) aneurysms, and in 1 (2.1%) case occlusion was not attempted. Procedure
      related permanent morbidity was 4.3%, and the mortality rate was 0%. There was no
      rebleeding of treated aneurysms. Complete occlusion at initial treatment (P =
      .003) and recanalization rate (P = .008) correlated with aneurysm sac size. A
      statistically significant relationship between Hunt and Hess/World Federation of
      Neurologic Surgeons clinical grading scale score and clinical outcome (Glasgow
      Outcome Score) was found (P < .05). Subgroup analysis revealed that a higher
      initial obliteration rate of larger aneurysms was achieved in group 2 (3D GDC, 22
      patients, 22 aneurysms) than in group 1 (23 patients, 24 aneurysms; P = .03). At
      angiographic follow-up, overall recanalization was 47.1% in group 2 and 47.6% in
      group 1. Aneurysm neck size was not found to be correlated with occlusion and
      recanalization rate. CONCLUSION: In our series, GDC technology was an effective
      and safe technique for the treatment of posterior circulation aneurysms. Aneurysm
      sac size was predictive for occlusion rate and the Hunt and Hess/World Federation
      of Neurologic Surgeons grade for clinical outcome. The introduction of 3D GDCs
      into our practice significantly improved the initial occlusion rate but did not
      affect the incidence of recanalization.

PMID- 16091523
TI  - Early rebleeding after coiling of ruptured cerebral aneurysms: incidence,
      morbidity, and risk factors.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to assess the incidence of
      early rebleeding after coiling of a ruptured cerebral aneurysm, assess the
      clinical outcome, and identify risk factors for this event. METHODS: Early
      rebleedings occurred in 6/431 (1.4%) consecutive patients after coiling of a
      ruptured aneurysm. Clinical condition at the time of treatment, aneurysm location
      and size, initial aneurysm occlusion, timing of coiling, and the presence of an
      adjacent intracerebral hematoma in the six patients with early rebleedings were
      compared with the remaining 425 patients. RESULTS: Incidence of early rebleeding
      after coiling of a ruptured aneurysm was 1.4%, and mortality was 100%.
      Independent risk factors are the presence of an adjacent intracerebral hematoma
      and small aneurysm size. Dependent risk factors are location on the anterior
      communicating artery, initial incomplete aneurysm occlusion, and poor clinical
      condition at the time of treatment. CONCLUSION: Early rebleeding after coiling of
      ruptured aneurysms is a major concern, in particular because the mortality is
      very high. A more restricted postembolization anticoagulation strategy in high
      risk aneurysms may possibly prevent the occurrence of this devastating event.

PMID- 16091524
TI  - Abciximab in patients with ruptured intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: Experience with intravenous abciximab to manage
      thromboembolism during treatment of ruptured intracranial aneurysms is limited.
      We present our experience in 13 patients. METHODS: We retrospectively reviewed
      all patients with thromboembolic complications during endovascular management of
      ruptured intracranial aneurysms. Thromboembolic complications were treated with
      intravenous abciximab. We recorded patient and aneurysm demographics, aneurysm
      occlusion, drug therapy, complications, and outcomes. RESULTS: World Federation
      of Neurological Surgeons Grades were 1 or 2 in 11 patients (85%). Median time
      from diagnostic angiography to treatment was 1 day. Ten (77%) aneurysms involved
      the anterior or posterior communicating artery, and one each occurred in the
      posterior inferior cerebellar artery, middle cerebral artery, and basilar
      regions. Eleven aneurysms were <10 mm. Five were incompletely occluded (0%-90%
      treated) at the time of the complication. Thromboembolic complications were at
      the coil-ball/parent-artery interface in nine patients (69%). Two were associated
      with coil-loop prolapse; one was prophylactically treated without evidence of
      thromboembolism. Five patients (38%) had distal complications; one also had a
      proximal thrombus. All patients received an intravenous bolus of abciximab (5-10
      mg in 92%) without infusion. Postprocedural recanalization was complete in eight
      (62%) and partial in four (31%). Eleven patients (85%) had a Glasgow Outcome
      Scale score of 1 at 3 months. One had a poor outcome (GOS4). One died following
      additional coiling after abciximab administration, though this intervention was
      uneventful in three others. CONCLUSION: Abciximab completely or partially treated
      thromboembolic complications arising during coiling of ruptured aneurysms.
      Further coiling should be performed with extreme caution and needs to be decided
      on a patient-by-patient basis.

PMID- 16091525
TI  - Initial clinical experience with a new self-expanding nitinol stent for the
      treatment of intracranial cerebral aneurysms: the Cordis Enterprise stent.
AB  - BACKGROUND AND PURPOSE: A new neurovascular microstent, the Cordis Enterprise
      stent, composed of nitinol, with a closed cell design, was specifically developed
      for the treatment of wide-necked intracranial cerebral aneurysms. The purpose of
      this study was to evaluate the safety, feasibility, and initial clinical results
      of using this device in patients. METHODS: In clinical evaluation, five patients
      ranging in age from 54 to 71 years were electively treated. The smallest aneurysm
      measured 3.3 x 2.9 mm, and the largest aneurysm measured 10.6 x 8.5 mm (neck and
      height measurements). RESULTS: All five cases (100%) were technically successful
      without complications. In each case, the stent was accurately placed in the
      desired location, immediately followed by coil embolization to the desired degree
      of occlusion with a satisfactory result. The poststent and coil-occlusion
      angiogram demonstrated excellent blood flow across the stent, with satisfactory
      positioning of the coils within the aneurysm in all cases (100%). No patient
      suffered any clinical or neurologic complications, and all were discharged 1-3
      days postprocedure, in stable condition with no new neurologic deficits.
      CONCLUSION: In early clinical studies, the Cordis Enterprise stent performed
      well. The stent was able to be well visualized, deployed easily, could be
      repositioned if needed, and was accurately placed without technical difficulties.
      The closed cell design allowed all coils to be placed within the aneurysm and
      remain outside the flow of the parent artery. No periprocedural complications
      were encountered.

PMID- 16091526
TI  - Angiographic and histologic analysis of experimental aneurysms embolized with
      platinum coils, Matrix, and HydroCoil.
AB  - BACKGROUND AND PURPOSE: A report directly comparing platinum coils, Matrix coils,
      and HydroCoils in a single animal model does not currently exist. We evaluated
      and compared the performance of these three products in the embolization of
      experimental aneurysms. METHODS: Thirty-three elastase-induced saccular aneurysms
      were created in rabbits. Aneurysms were embolized with Matrix coils (n = 15),
      HydroCoils (n = 9), or platinum coils (n = 9). The groups were compared with
      respect to the following parameters: aneurysm size, procedure duration, number
      and total length of devices deposited, angiographic occlusion score, and
      volumetric occlusion percentage. Follow-up angiographic and histologic features
      at 2, 6, and 10 weeks after embolization were analyzed. Groups were compared by
      using analysis of variance and chi2 tests. RESULTS: No significant differences
      were found among groups regarding aneurysm size, total device length, initial
      angiographic occlusion score, or procedure time. The mean number of devices for
      Matrix subjects was less than that for platinum coils (P = .02) and HydroCoil (P
      = .03). Volumetric occlusion for HydroCoil (76%) was significantly greater (P <
      .0001) than both platinum coils (31%) and Matrix (23%). Angiographic durability
      was significantly increased in the HydroCoil group compared with Matrix (P =
      .03). Coil compaction was found more frequently in the Matrix group (five cases,
      33%) than the HydroCoil (no cases, 0%), or platinum coil groups (two cases, 22%).
      The Matrix group showed greater tissue reaction compared with platinum coils (P <
      .05). CONCLUSION: In the rabbit model, the use of HydroCoils results in improved
      long-term occlusion rates compared with Matrix and platinum coils. The Matrix
      group showed an increase in inflammation and coil compaction compared with
      HydroCoils and platinum coils.

PMID- 16091527
TI  - Creation of four experimental aneurysms with different hemodynamics in one dog.
AB  - We developed an experimental canine model in which four types of aneurysm-
      bifurcation, side-wall, small branch-artery, and arterial-stump--were surgically
      created in the same animal. These experimental aneurysms are exposed to
      simultaneous but different hemodynamic stresses correlating to human intracranial
      aneurysms in different locations. Because this model allowed for the creation of
      four aneurysms, each with different hemodynamic features, it seems to offer
      advantages from ones previously described. This model may foster investigation of
      new and current endovascular devices.

PMID- 16091528
TI  - Double-balloon remodeling of wide-necked aneurysms distal to the circle of
      Willis.
AB  - We describe a remodeling technique in which two compliant balloon catheters were
      used to treat large, wide-necked bifurcation aneurysms distal to the circle of
      Willis in two patients with subarachnoid hemorrhage. Although vasospasm and
      interaction between the constrained catheters in the small distal arteries added
      to the complexity of the procedure, placement of a balloon catheter in each side
      branch prevented coil encroachment and enabled embolization of these aneurysms.

PMID- 16091529
TI  - Effects of carotid or vertebrobasilar stent placement on cerebral perfusion and
      cognition.
AB  - INTRODUCTION: There are no well-established physiologic or neuropsychological
      criteria for identifying which patients with stenosis of the cervicocerebral
      vessels are at high risk of stroke or cognitive impairment. Our purpose was to
      evaluate changes in cognitive performance and cerebral perfusion associated with
      endovascular stent placement of the cervicocerebral vessels. METHODS: A
      consecutive series of 20 patients, 31-88 years of age, who underwent 21 stent
      procedures for arterial stenosis (10 extracranial carotid stents [ECS], four
      intracranial carotid stents [ICS], and seven extra- or intracranial
      vertebrobasilar stents [VBS]) was investigated retrospectively. All patients were
      evaluated with CT or MR perfusion studies both before and after stent placement.
      Cognitive response after stent placement was evaluated by using an informant
      questionnaire. RESULTS: In patients with anterior circulation stenoses (ECS and
      ICS group), 11 of 14 (79%) had a baseline perfusion abnormality and all 11
      patients showed improved perfusion after stent placement. Four of seven (57%)
      patients with posterior circulation stenoses (VBS group) had a baseline perfusion
      abnormality and two of the four patients showed improved perfusion after stent
      placement. Degree of stenosis was the strongest predictor of the presence of a
      baseline perfusion abnormality (P = .03). Fifteen of 19 (79%) of the patients
      showed improved cognitive scores after stent placement. Among patients with
      improvement in perfusion after stent placement, 11 of 13 (85%) had improved
      cognitive scores. Improved perfusion after stent placement was a significant
      predictor of cognitive improvement (P = .04). Patients who were stented on an
      elective basis demonstrated greater improvement in cognition as compared with
      patients stented urgently (P = .01). CONCLUSION: Endovascular stent placement of
      the cervicocerebral vessels can safely and effectively resolve cerebral perfusion
      abnormalities. Improvement in perfusion parameters is associated with cognitive
      improvement. Larger, blinded, prospective studies are needed to confirm these
      preliminary observations.

PMID- 16091530
TI  - Outcomes of carotid angioplasty and stenting for radiation-associated stenosis.
AB  - BACKGROUND AND PURPOSE: In light of their high surgical risk, carotid angioplasty
      and stent placement may be preferred in patients with radiation-associated
      carotid stenosis. The purpose of this study was to determine the procedural
      complication rate, patency, and clinical outcomes after carotid angioplasty and
      stent placement in this small group of high-risk patients. METHODS: Sixteen
      patients (mean age, 65 years; 5 women and 11 men) who received radiation therapy
      for head and/or neck malignancy subsequently developed carotid stenosis (mean,
      84%; range, 70%-99%) in a total of 19 carotid arteries, which were treated with
      angioplasty and stent placement. The patients were followed for a mean time of 28
      months (range, 5-78 months) with periodic Doppler studies, angiography, CT
      angiography, or clinically. RESULTS: In the total 19 stented carotid arteries, 23
      procedures were performed (22 stent placement procedures and one repeat
      angioplasty). The procedural stroke rate was 1/23 (4%). The procedural transient
      ischemic attack rate was 0/23 (0%). There was one other observed complication: a
      puncture site hematoma. The 30-day postprocedure complication rate was 0/23 (0%);
      no neurologic symptoms were reported. Fifteen of the 19 vessels (79%) developed
      no new stenosis throughout the follow-up period. Two of 19 (11%) vessels had
      repeat angioplasty and stent placement; 1/19 (5%) had a repeat angioplasty. One
      restented vessel has remained patent for 50 months. Another restented vessel
      required a third stent placement 17 months after the second. Two of 19 (11%)
      vessels occluded per Doppler examination 14 and 22 months postprocedure.
      CONCLUSION: Angioplasty and stent placement have low rates of complications and
      restenosis in the treatment of radiation-associated carotid occlusive disease.

PMID- 16091531
TI  - Angiographic assessment of pial collaterals as a prognostic indicator following
      intra-arterial thrombolysis for acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: This study examines whether anatomic extent of pial
      collateral formation documented on angiography during acute thromboembolic stroke
      predicts clinical outcome and infarct volume following intra-arterial
      thrombolysis, compared with other predictive factors. METHODS: Angiograms, CT
      scans, and clinical information were retrospectively reviewed in 65 consecutive
      patients who underwent thrombolysis for acute ischemic stroke. Clinical data
      included age, sex, time to treatment, National Institutes of Health Stroke Scale
      (NIHSS) score on presentation of symptoms, NIHSS score at the time of hospital
      discharge, and modified Rankin scale score at time of hospital discharge. Site of
      occlusion, scoring of anatomic extent of pial collaterals before thrombolysis,
      and recanalization (complete, partial, or no recanalization) were determined on
      angiography. Infarct volume was measured on CT scans performed 24-48 hours after
      treatment. RESULTS: Fifty-three patients (82%) qualified for review. Both infarct
      volume and discharge modified Rankin scale scores were significantly lower for
      patients with better pial collateral scores than those with worse pial collateral
      scores, regardless of whether they had complete (P < .0001) or partial (P =
      .0095) recanalization. Adjusting for other factors, regression analysis models
      indicate that the infarct volume was significantly larger (P < .0001) and
      modified discharge Rankin scale score and discharge NIHSS score significantly
      higher for patients with worse pial collateral scores. Similarly, adjusting for
      other factors, the infarct volume was significantly lower (P = .0006) for
      patients with complete recanalization than patients with partial or no
      recanalization. CONCLUSIONS: Evaluation of pial collateral formation before
      thrombolytic treatment can predict infarct volume and clinical outcome for
      patients with acute stroke undergoing thrombolysis independent of other
      predictive factors. Thrombolytic treatment appears to have a greater clinical
      impact in those patients with better pial collateral formation.

PMID- 16091532
TI  - Hypoattenuation on CT angiographic source images predicts risk of intracerebral
      hemorrhage and outcome after intra-arterial reperfusion therapy.
AB  - BACKGROUND AND PURPOSE: Symptomatic hemorrhagic transformation (HT) is a
      significant complication of intravenous and catheter-based reperfusion. We
      hypothesized that the degree of vascular insufficiency, reflected as
      hypoattenuation on initial CT angiography (CTA) axial source images, is
      predictive of HT risk in stroke patients receiving intra-arterial reperfusion
      therapy. METHODS: We examined initial CTA source images and follow-up CT scans in
      32 consecutive patients. Regions of interest were semiautomatically segmented and
      reviewed. Mean intensity was determined in the region of maximal hypoattenuation
      and in normal contralateral tissue, and the arithmetic difference (deltaHU)
      calculated. Receiver operator characteristic (ROC) curves and cross-validation
      were used to identify threshold deltaHU values. RESULTS: Thirteen patients had HT
      on follow-up CT (seven with parenchymal hematoma, six with hemorrhagic
      infarction). Patients with and those without HT did not differ in age, blood
      glucose level, lesion volume, or time to treatment or recanalization, though the
      former had a greater mean deltaHU (9.0 vs 6.3, P = .006). The ROC threshold at
      deltaHU > or = 8.1 was 69% sensitive and 90% specific for patients who developed
      HT (odds ratio = 19.1; 95% confidence interval: 2.9, 125; P = .002) and was
      predictive of poor clinical outcome (modified Rankin scale score > 2, P = .03).
      Neither HT in general nor parenchymal hematoma subtype was associated with poor
      outcome. CONCLUSION: The degree of hypoattenuation on initial CTA source images
      is a risk factor for HT and poor clinical outcome after intra-arterial
      reperfusion therapy. Prospective validation of this relationship in large
      populations may permit feasible real-time risk stratification.

PMID- 16091533
TI  - Intra-arterial high-dose chemotherapy with cisplatin as part of a palliative
      treatment concept in oral cancer.
AB  - BACKGROUND AND PURPOSE: Patients with cancer of the oral cavity often present
      with advanced tumor stages, distant metastasis, or severe comorbidities, which
      render radical surgery unfeasible. The purpose of this study was to investigate
      the response rate, technical feasibility, and safety of intra-arterial (IA)
      chemotherapy as palliative treatment in this situation. METHODS: From November
      1997 to December 2003, 64 patients with histologically proven oral squamous cell
      carcinoma, classified as inoperable, received IA high-dose chemotherapy with
      cisplatin as a palliative treatment at our institution. To minimize toxic side
      effects, sodium thiosulfate was given intravenously. Twenty-eight percent of the
      patients were female; average age was 61.5 years. Clinical staging of primary
      tumors was TNM (tumor, nodules, metastases) stage IV in 89%, stage III in 6.3%
      and stage II in 4.7%. After local chemotherapy, additional radiation of the tumor
      area or radiochemotherapy was performed in 33 patients. RESULTS: There were no
      major catheter-related complications or severe side effects of IA chemotherapy.
      After the first cycle, 10% percent of the patients had complete remission (CR),
      35% had partial response (PR), and 43.3% presented with stable disease. Mean
      follow-up interval was 11 +/- 12.9 months. Forty-five patients died after a mean
      period of 7.6 +/- 7.0 months (median, 5.1 months). The overall 1- and 2-year
      survival rates were 29.5% and 18%, respectively. There was a trend toward longer
      survival in patients who received subsequent radiation or radiochemotherapy after
      IA chemotherapy. CONCLUSION: IA chemotherapy in patients with inoperable
      carcinoma of the oral cavity as palliative treatment was technically feasible and
      safe. The overall response rate after IA chemotherapy was 45% (CR 10%; PR 35%).
      Side effects could be minimized by neutralizing the cytotoxic agent by sodium
      thiosulfate.

PMID- 16091534
TI  - Use of a pressure-sensing wire to detect sequential pressure gradients for
      ipsilateral vertebral and subclavian artery stenoses.
AB  - Endoluminal stent placement is safe and effective in the treatment of symptomatic
      ostial stenoses of the vertebral artery (VA) and proximal subclavian artery
      (SCA). However, determining the relative importance of an individual lesion on
      angiography is difficult when VA and SCA stenoses are concurrent. Pressure
      sensing wires help in determining the functional significance of coronary artery
      stenosis. We present a case of ipsilateral VA and SCA stenoses in which a
      pressure-sensing wire was used in making interventional decisions.

PMID- 16091535
TI  - Angiographic CT in cerebrovascular stenting.
AB  - We evaluated the feasibility of angiographic CT (ACT) for visualizing metallic
      stents in three patients who underwent intracranial (n = 2) or extracranial (n =
      1) stent placement to treat atherosclerotic lesions. ACT is a new technique that
      provides cross-sectional CT-like images based on rotational radiography performed
      with a rotating C-arm-mounted flat-panel detector. ACT allowed for the clear
      visualization of stents in both intracranial and extracranial arteries and was
      superior to conventional digital subtraction angiography and digital radiography
      in visualizing both the stent struts and their relationships to the arterial
      walls and aneurysmal lumen.

PMID- 16091536
TI  - Functional heterogeneity of the supplementary motor area.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to assess supplementary
      motor area (SMA) activation during motor, sensory, word generation, listening
      comprehension, and working memory tasks by using functional MR imaging (fMRI).
      Human supplementary motor area (SMA) has been shown to play roles in motor
      control and other various functions such as sensory, speech expression, and
      memory. However, topographical localizations of these functions in the SMA remain
      unclear. The purpose of this study was to assess SMA activation during motor,
      sensory, word generation, listening comprehension, and working memory tasks by
      using functional MR imaging (fMRI). METHODS: Sixteen healthy right-handed
      subjects (nine men and seven women) were imaged on a Siemens 1.5T system. Whole
      brain functional maps were acquired by using blood oxygenation level-dependent
      echo-planar imaging sequences in the axial plane. Each paradigm consisted of five
      epochs of activation versus the control condition. The activation tasks consisted
      of left-finger complex movement, heat sensory stimulation of the left hand, word
      generation, listening comprehension, and working memory. The reference function
      was a boxcar waveform. Activation maps were thresholded at an uncorrected P =
      .0001. The thresholded activation maps were placed into MNI (Montreal Neurologic
      Institute) stereotactic coordinates, and the anatomic localization of activation
      within the SMA was compared across tasks. RESULTS: SMA activation was observed in
      16 volunteers for the motor task, 11 for the sensory task, 15 for the word
      generation task, five for the listening comprehension task, and 15 for the
      working memory task. Although not statistically significant, qualitative
      differences in the location of activation within the SMA were present by task.
      The rostral aspects of the SMA tended to activate during word generation and
      working memory tasks, and the caudal aspect of the SMA tended to activate during
      the motor and sensory tasks. Right (contralateral) SMA activation was observed
      during the motor and sensory tasks, and left SMA activation during the word
      generation and memory tasks. CONCLUSION: Our results suggest that SMA is involved
      in a variety of functional tasks, including motor, sensory, word generation, and
      working memory. Some are tasks that are traditionally associated with this area
      (such as motor and sensory), and others are not (such as word generation and
      working memory). Qualitatively, the anterior and posterior portions of the SMA
      appeared to be engaged by different types of tasks.

PMID- 16091537
TI  - Regional lobar atrophy predicts memory impairment in multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: In recent studies, measures of whole brain atrophy were
      strongly correlated with neuropsychological testing, explaining more variance
      than measures of lesion burden in patients with multiple sclerosis. The
      relationship between regional lobar atrophy and cognitive impairment is yet to be
      examined. We endeavored to assess the clinical significance of regional lobar
      atrophy in multiple sclerosis. METHODS: In a cross-sectional study, we evaluated
      31 patients with multiple sclerosis with brain MR imaging and neuropsychological
      testing. Impairment was determined by comparison with demographically matched
      healthy controls. MR imaging generated measures of lesion burden (fluid
      attenuated inversion recovery hyperintense volume), general atrophy (brain
      parenchymal fraction), central atrophy (lateral ventricle volume), and lobar
      atrophy (regional brain parenchymal fraction of frontal, temporal, parietal, and
      occipital lobes in each hemisphere). Neuropsychological testing emphasized
      measures of processing speed and memory, because these are commonly affected in
      multiple sclerosis. RESULTS: Patients with multiple sclerosis showed significant
      atrophy and impairment on all neuropsychological tests. Regional atrophy
      accounted for the most variance in all regression models predicting memory
      performance. Left temporal atrophy was the primary predictor of auditory/verbal
      memory (partial r's = 0.55-0.61), and both left and right temporal atrophy
      predicted visual/spatial memory performance (partial r's = 0.51-0.67). Models
      predicting learning consistency retained frontal lobe atrophy measures (partial
      r's = 0.44-0.68). Central and general atrophy measures were the primary
      predictors in modeling processing speed (partial r's = 0.42-0.64). CONCLUSION:
      Regional atrophy accounts for more variance than lesion burden, whole brain
      atrophy, or lateral ventricle volume in predicting multiple sclerosis-associated
      memory dysfunction.

PMID- 16091538
TI  - Correlation of apparent diffusion coefficient with neuropsychological testing in
      temporal lobe epilepsy.
AB  - BACKGROUND AND PURPOSE: Patients with nonlesional temporal lobe epilepsy have
      long been known to have abnormalities of memory. Recently, these patients have
      been shown to have increased diffusivity in the hippocampus. We hypothesized that
      in these patients, a negative correlation would exist between diffusivity
      measures of the mesial temporal lobe and performance on neuropsychological tests.
      METHODS: Twenty presurgical patients with temporal lobe epilepsy and 20 age- and
      sex-matched healthy controls underwent MR imaging of the brain. Apparent
      diffusion coefficient region of interest measures were taken in both hippocampi
      and parahippocampal gyri by 2 independent observers. Mean whole brain diffusivity
      was calculated. All patients completed neuropsychological testing.
      Electroencephalogram and pathology results were collected. Patients and controls
      were compared with respect to each apparent diffusion coefficient measure. In
      patients, apparent diffusion coefficients ipsilateral and contralateral to the
      seizure focus were compared. Associations were assessed between diffusivity
      measures and neuropsychological scores. RESULTS: Eleven patients had right-sided
      seizure foci and 9 had left-sided seizure foci. Patients demonstrated higher
      apparent diffusion coefficient values than controls over the whole brain, in the
      hippocampi, and in the parahippocampal gyri (P < .05). Patients demonstrated
      higher apparent diffusion coefficient within the ipsilateral hippocampus (1.19 +/
      0.22 x 10(-3) s/mm2) and parahippocampal gyrus (1.02 +/- 0.12 x 10(-3) s/mm2)
      compared with the contralateral side (1.02 +/- 0.16 x 10(-3) s/mm2 and 0.96 +/-
      0.09 x 10(-3) s/mm2, respectively) (P < .05). Negative correlations were seen
      between hippocampal apparent diffusion coefficients and multiple memory tests (P
      < .05). CONCLUSION: Quantitative diffusion measurements in the hippocampus
      correlate with memory dysfunction in patients with temporal lobe epilepsy.

PMID- 16091539
TI  - MR diffusion tensor imaging, fiber tracking, and single-voxel spectroscopy
      findings in an unusual MELAS case.
AB  - A 23-year-old man was admitted to the intensive care unit for respiratory
      failure, global lower and upper limb palsy, and higher cognitive function
      deterioration. Imaging, performed with a combination of the MR diffusion tensor
      imaging, fiber tracking, and MR spectroscopy, suggested the diagnosis of an acute
      severe unusual mitochondrial encephalopathy, lactic acidosis, and strokelike
      event, which was confirmed by muscle biopsy, but fiber tracking showed unexpected
      unaltered white matter tracts.

PMID- 16091540
TI  - Pallidoreticular damage in acute carbon monoxide poisoning: diffusion-weighted MR
      imaging findings.
AB  - We describe a case of carbon monoxide poisoning that led to pallidoreticular
      damage and delayed leukoencephalopathy. Serial diffusion-weighted MR imaging was
      performed. A restricted water diffusion pattern was demonstrated in the globus
      pallidus and substantia nigra in the early stage. Diffusion-weighted imaging is
      useful for early identification of the effects of acute carbon monoxide
      poisoning.

PMID- 16091541
TI  - Ruptured aneurysm of the anomalous cerebellar artery originating from internal
      carotid artery presenting with carotid cavernous fistula: a case report.
AB  - We report a case of a ruptured aneurysm of the anomalous cerebellar artery
      originating from internal carotid artery presenting with a carotid cavernous
      fistula (CCF). An initial angiogram showed the typical appearance of a CCF with a
      direct fistulous tract with focal aneurysmal dilation from the ascending
      cavernous segment of the right internal carotid artery. A postembolization
      angiogram of the right internal carotid disclosed the anomalous cerebellar artery
      originating from the fistula point of the internal carotid artery.

PMID- 16091542
TI  - Linear accelerator-based radiosurgery for multiple arteriovenous malformations:
      case report.
AB  - This report presents a rare case of multiple, widely spaced arteriovenous
      malformations in a single patient treated with linear accelerator-based
      radiosurgery. The choices associated with the requisite imaging and planning are
      presented. In light of the anatomic topography, linear accelerator-based
      radiosurgery was chosen over gamma knife treatment, with CT angiography being
      used to image all target areas simultaneously.

PMID- 16091543
TI  - Temporal lobe intraparenchymal retained foreign body from remote orbital trauma.
AB  - We present the case of a 35-year-old man with a new onset of seizure disorder who
      was found to harbor an intraparenchymal retained foreign body related to remote
      orbital trauma. Imaging revealed a rim-enhancing anterior medial temporal lobe
      mass. Histologic evaluation of the resected mass showed evidence of acute and
      chronic inflammation with associated foreign material. The patient described a
      "bar fight" 16 years previously in which he received a blow to the orbit with a
      pool cue stick. The diagnosis of a foreign body reaction should be considered
      when an intraparenchymal mass is identified in this location.

PMID- 16091544
TI  - Posterior pituitary astrocytoma: a rare tumor of the neurohypophysis: a case
      report.
AB  - Astrocytoma, or pituicytoma, of the posterior pituitary is a relatively rare
      entity consisting of poorly characterized glial tumor cells. We report two cases
      of posterior pituitary astrocytomas in middle-aged women presenting as focal
      lesions of the neurohypophysis. A review of the literature reveals only a few
      reports of this tumor, and there has been scanty discussion of the imaging
      findings of posterior pituitary astrocytomas compared with lesions of the
      anterior pituitary gland. This report reviews the clinical characteristics and
      imaging findings and discusses the differential diagnosis of these two cases.

PMID- 16091545
TI  - Second brachial cleft cyst mimic: case report.
AB  - We report the CT findings in a patient with a lateral neck mass histologically
      shown to be a schwannoma but having certain radiographic features commonly
      considered pathognomonic for a type III second branchial cleft cyst. Our case,
      therefore, represents an exception to this long-established rule.

PMID- 16091546
TI  - Bifid mandibular condyle: CT and MR imaging appearance in two patients: case
      report and review of the literature.
AB  - We describe two cases of a bifid mandibular condyle. The first case is a 48-year
      old woman with headaches and a pain and clicking sensation in her right jaw
      during mastication. The second case is an asymptomatic 17-year-old woman with a
      history of bilateral microtia and hemifacial microsomia. In both patients, the
      bifid condyle was first identified by CT and affected the temporomandibular
      joint. The imaging findings of both patients' bifid mandibular condyles led us to
      conclude that both patients likely had an abnormal development of the mandibular
      condyles. We believe that an intervening fibrous or vascular structure may have
      split the condyle into two heads.

PMID- 16091547
TI  - Diffusion-weighted imaging, apparent diffusion coefficients, and fluid-attenuated
      inversion recovery MR imaging in endophthalmitis.
AB  - We describe the appearance of endogenous bacterial endophthalmitis in a patient
      who underwent MR imaging of the orbits before and during the course of treatment.
      Intraocular hyperintensity on fluid-attenuated inversion recovery and diffusion
      weighted images were found very useful for diagnosing endophthalmitis. After a
      few days of treatment, a marked relative increase in intraocular mean apparent
      diffusion coefficient values was observed, which appears to indicate good
      treatment response.

PMID- 16091548
TI  - Transalar encephalocele associated with Wegener granulomatosis and meningeal
      enhancement: case report.
AB  - Transalar encephaloceles are rare lesions that do not fit the standard
      classification of basal encephaloceles. Typically, these lesions present in
      adulthood, with nonspecific symptoms. We report here a case of a patient with
      Wegener disease in whom a large transalar encephalocele posterior to the sinus
      was noted when he was preoperative for left maxillary sinus surgery. The
      encephalocele demonstrated irregular peripheral enhancement along the margin--a
      very uncommon finding--as well as contrast enhancement of the basal meninges,
      which can be seen occasionally with Wegener granulomatosis.

PMID- 16091549
TI  - Posterior column involvement in Miller Fisher syndrome or dorsal root ganglion
      neuronopathy?

PMID- 16091550
TI  - Questionable interpretation of results of ACTIVE study on Matrix coils by Boston
      Scientific.

PMID- 16091551
TI  - Concha bullosa and nasal septal deviation.

PMID- 16091552
TI  - Fatal Ethibloc embolization of vertebrobasilar system following percutaneous
      injection into aneurysmal bone cyst of the second cervical vertebra.

PMID- 16091553
TI  - Gastroprotective effects of oral nucleotide administration.
AB  - BACKGROUND AND AIMS: Nucleotides form the building blocks of DNA and are marketed
      as dietary supplements, alone or in combination with other ingredients, to
      promote general health. However, there has been only limited scientific study
      regarding the true biological activity of orally administered nucleotides. We
      therefore tested their efficacy in a variety of models of epithelial injury and
      repair. METHODS: Effects on proliferation ([3H] thymidine incorporation) and
      restitution (cell migration of wounded monolayers) were analysed using HT29 and
      IEC6 cells. The ability of a nucleotide mixture to influence gastric injury when
      administered orally and subcutaneously was analysed using a rat indomethacin (20
      mg/kg) restraint model. RESULTS: In both cell lines, cell migration was increased
      by approximately twofold when added at 1 mg/ml (p<0.01); synergistic responses
      were seen when a mixture of nucleotides was used. Cell proliferation was
      stimulated by adenosine monophosphate (AMP) in HT29, but not in IEC6, cells.
      Gastric injury was reduced by approximately 60% when gavaged at 4-16 mg/ml
      (p<0.05), concentrations similar to those likely to be found in consumers taking
      nucleotide supplements. Systemic administration of nucleotides was unhelpful.
      CONCLUSIONS: Nucleotides possess biological activity when analysed in a variety
      of models of injury and repair and could provide a novel inexpensive approach for
      the prevention and treatment of the injurious effects of non steroidal anti
      inflammatory drugs and other ulcerative conditions of the bowel. Further studies
      on their potential benefits (and risks) appear justified.

PMID- 16091554
TI  - Multimodal pain stimulations in patients with grade B oesophagitis.
AB  - AIM: To obtain a better understanding of nociceptive processing in patients with
      oesophagitis. PATIENTS AND METHODS: Eleven patients with grade B oesophagitis
      were compared with an age and sex matched group of 16 healthy subjects. A probe
      was positioned in the lower part of the oesophagus. After preconditioning of the
      tissue, painful mechanical stimuli were applied as distensions with a bag using
      an impedance planimetric method. Distensions were done before and after
      pharmacological impairment of distension induced smooth muscle contractions.
      Thermal stimulation was performed by recirculating water at 1 and 60 degrees C in
      the bag. The area under the temperature curve (AUC) represented caloric load. The
      referred pain area (being a proxy for the central pain mechanisms) to the
      mechanical stimuli was drawn at maximum pain intensities. RESULTS: Patients were
      hyposensitive to mechanical stimuli, as assessed by the distending volume (F=8.1,
      p=0.005). After relaxation of smooth muscle with butylscopolamine, the difference
      between the two groups was more evident (F=27.4, p<0.001). AUC for cold
      stimulation was 1048.6 (242.7) degrees Cxs in controls and 889.8 (202.6) degrees
      Cxs in patients (p=0.5). For heat stimuli, AUC values were 323.3 (104.1) and 81.3
      (32.3) degrees Cxs in controls and patients, respectively (p=0.04). The referred
      pain area to the mechanical stimulations was larger and more widespread in
      patients (49.3 (6.2) cm2 compared with controls 23.9 (7) cm2; p=0.02).
      CONCLUSIONS: The data indicate that peripheral sensitisation of heat sensitive
      receptors and pathways combined with facilitation of central pain mechanisms may
      explain the symptoms in patients with oesophagitis.

PMID- 16091555
TI  - Attenuation of acid induced oesophagitis in VR-1 deficient mice.
AB  - BACKGROUND AND AIMS: Activation of the vanilloid receptor subtype 1 (VR-1)
      results in release of proinflammatory peptides which initiate an inflammatory
      cascade known as neurogenic inflammation. We investigated its role in an acute
      model of surgically induced oesophagitis. METHODS: Oesophagitis was induced by
      pyloric ligation in wild-type and VR-1 deficient mice. A subset of animals were
      administered the VR-1 antagonist capsazepine, famotidine, or omeprazole one hour
      before surgery. Five hours after surgery, myeloperoxidase activity (MPO),
      histological damage scores, intragastric pH, and immunocytochemical analysis of
      substance P (SP) receptor endocytosis were determined. RESULTS: Oesophagitis
      induced knockout mice exhibited significantly lower levels of MPO activity,
      histological damage scores, and SP receptor endocytosis than wild-type mice.
      Inflammatory parameters were significantly reduced by acid inhibition and
      capsazepine in wild-type mice. CONCLUSIONS: We conclude that acute acid induced
      oesophagitis is reduced in animals lacking VR-1. This suggests that acid induced
      oesophagitis may act through VR-1 and that inhibition of the receptor may reduce
      inflammation.

PMID- 16091556
TI  - Simple and efficient isolation of hematopoietic stem cells from H2K-zFP
      transgenic mice.
AB  - We have generated a transgenic mouse line that allows for simple and highly
      efficient enrichment for mouse hematopoietic stem cells (HSCs). The transgene
      expresses a green fluorescent protein variant (zFP) under the control of H2Kb
      promoter/enhancer element. Despite the broad zFP expression, transgenic HSCs
      express exceptionally high levels of zFP, allowing prospective isolation of a
      population highly enriched in HSCs by sorting the 0.2% of the brightest green
      cells from the enriched bone marrow of H2K-zFP mice. Up to 90% of zFP(bright)
      cells are also c-kit(high), Sca-1(high), Lin(neg), Flk-2(neg), which is a bona
      fide phenotype for long-term HSCs. Double-sorted zFP(bright) HSCs were capable of
      long-term multilineage reconstitution at a limiting dilution dose of
      approximately 12 cells, which is comparable to that of highly purified HSCs
      obtained by conventional multicolor flow cytometry. Thus, the H2K-zFP transgenic
      mice provide a straightforward and easy setup for the simple and highly efficient
      enrichment for genetically labeled HSCs without using fluorescence-conjugated
      monoclonal antibodies. This approach will greatly facilitate gene transfer,
      including short interfering RNA for gene knockdown, into HSCs and, consequently,
      into all other hematopoietic lineages.

PMID- 16091557
TI  - Electrophysiological properties of pluripotent human and mouse embryonic stem
      cells.
AB  - Pluripotent embryonic stem cells (ESCs) possess promising potential for cell
      based therapies, but their electrophysiological properties have not been
      characterized. Here we describe the presence of ionic currents in mouse (m) and
      human (h) ESCs and their physiological function. In mESCs, tetraethylammonium
      (TEA)-sensitive depolarization-activated delayed rectifier K+ currents (IK(DR))
      (8.6 +/- 0.9 pA/pF at +40 mV; IC50 = 1.2 +/- 0.3 mM), which contained components
      sensitive to 4-aminopyridine (4-AP) (IC50 = 0.5 +/- 0.1 mM) and 100 nM Ca2+
      activated K+ current (IK(Ca)) blocker iberiotoxin (IBTX),were detected in 52.3%
      of undifferentiated cells.IK(DR) was similarly present in hESCs (approximately
      100%) but with an approximately sixfold higher current density (47.5 +/- 7.9
      pA/pF at +40 mV). When assayed by bromodeoxyurindine incorporation, application
      of TEA, 4-AP, or IBTX significantly reduced the proliferation of mESCs and hESCs
      in a dose-dependent manner (p < .05). A hyperpolarization-activated inward
      current (I(h)) (-2.2 +/- 0.4 pA/pF at -120 mV) was detected in 23% of mESCs but
      not hESCs. Neither Na(v) nor Ca(v) currents were detected in mESCs and hESCs.
      Microarray and reverse transcription-polymerase chain reaction analyses
      identified several candidate genes for the ionic currents discovered.
      Collectively, our results indicate that pluripotent ESCs functionally express
      several specialized ion channels and further highlight similarities and
      differences between the two species. Practical considerations for the therapeutic
      use of ESCs are discussed.

PMID- 16091558
TI  - Fetal microchimerism in the maternal mouse brain: a novel population of fetal
      progenitor or stem cells able to cross the blood-brain barrier?
AB  - We investigated whether fetal cells can enter the maternal brain during
      pregnancy. Female wild-type C57BL/6 mice were crossed with transgenic Green Mice
      ubiquitously expressing enhanced green fluorescent protein (EGFP). Green Mouse
      fetal cells were found in the maternal brain. Quantitative real-time polymerase
      chain reaction (PCR) of genomic DNA for the EGFP gene showed that more fetal
      cells were present in the maternal brain 4 weeks postpartum than on the day of
      parturition. After an excitotoxic lesion to the brain, more fetal cells were
      detected in the injured region. The presence of fetal cells in the maternal brain
      was also confirmed by quantitative real-time PCR for the sex-determining region
      of the Y chromosome. Four weeks postpartum, EGFP-positive Green Mouse fetal cells
      in the maternal brain were found to adopt locations, morphologies, and expression
      of immunocytochemical markers indicative of perivascular macrophage-, neuron-,
      astrocyte-, and oligodendrocyte-like cell types. Expression of morphological and
      immunocytochemical characteristics of neuron- and astrocyte-like cell types was
      confirmed on identification of fetal cells in maternal brain by Y chromosome
      fluorescence in situ hybridization. Although further studies are required to
      determine whether such engraftment of the maternal brain has any physiological or
      pathophysiological functional significance, fetomaternal microchimerism provides
      a novel model for the experimental investigation of the properties of fetal
      progenitor or stem cells in the brain without prior in vitro manipulation.
      Characterization of the properties of these cells that allow them to cross both
      the placental and blood-brain barriers and to target injured brain may improve
      selection procedures for isolation of progenitor or stem cells for brain repair
      by intravenous infusion.

PMID- 16091559
TI  - The cover. Boats in Trouville Harbor.

PMID- 16091560
TI  - Hormone changes in aging adults probed.

PMID- 16091561
TI  - Researchers investigate factors linked to development of secondary diabetes.

PMID- 16091563
TI  - Volunteering overseas gives physicians a measure of adventure and altruism.

PMID- 16091562
TI  - Managing lipid levels in diabetes beneficial but requires clinical judgment.

PMID- 16091564
TI  - Study reveals mitochondrial role in aging.

PMID- 16091565
TI  - Racial differences in BRCA testing.

PMID- 16091566
TI  - Direct-to-consumer advertising and physician prescribing.

PMID- 16091567
TI  - Blood mercury levels and neurobehavior.

PMID- 16091568
TI  - Quality improvement organizations and the Institute of Medicine.

PMID- 16091569
TI  - Confidentiality and "Jambo, Jahi".

PMID- 16091570
TI  - Incidence of basal cell and squamous cell carcinomas in a population younger than
      40 years.
AB  - CONTEXT: The incidence of nonmelanoma skin cancer is increasing rapidly among
      elderly persons, but little is known about its incidence in the population
      younger than 40 years. OBJECTIVES: To estimate the sex- and age-specific
      incidences of basal cell carcinoma and squamous cell carcinoma in persons younger
      than 40 years in Olmsted County, Minnesota, and to evaluate change in incidence
      over time; to describe the clinical presentation, rate of recurrence and
      metastasis, and histologic characteristics of these tumors in this population
      based sample. DESIGN: Population-based retrospective incidence case review.
      SETTING: Residents of Olmsted County, Minnesota, a population with comprehensive
      medical records captured through the Rochester Epidemiology Project.
      PARTICIPANTS: Patients younger than 40 years with basal cell carcinoma or
      squamous cell carcinoma diagnosed between 1976 and 2003. MAIN OUTCOME MEASURES:
      Incident basal cell carcinomas and squamous cell carcinomas and change in
      incidence of these tumors over time. RESULTS: During the study period, 451
      incident basal cell carcinomas were diagnosed in 417 patients and 70 incident
      squamous cell carcinomas were diagnosed in 68 patients. Of these tumors, 328 were
      histologically confirmed basal cell carcinomas and 51 were histologically
      confirmed squamous cell carcinomas. Overall, the age-adjusted incidence of basal
      cell carcinoma per 100,000 persons was 25.9 (95% confidence interval [CI], 22.6
      29.2) for women and 20.9 (95% CI, 17.8-23.9) for men. The incidence of basal cell
      carcinoma increased significantly during the study period among women (P<.001)
      but not men (P = .19). Nodular basal cell carcinoma was the most common
      histologic subtype; 43.0% of tumors were solely nodular basal cell carcinoma and
      11.0% had a mixed composition, including the nodular subtype. The incidence of
      squamous cell carcinoma was similar in men and women, with an average age- and
      sex-adjusted incidence per 100 000 persons of 3.9 (95% CI, 3.0-4.8); the
      incidence of squamous cell carcinoma increased significantly over the study
      period among both women (P = .01) and men (P = .04). CONCLUSIONS: This population
      based study demonstrated an increase in the incidence of nonmelanoma skin cancer
      among young women and men residing in Olmsted County, Minnesota. There was a
      disproportionate increase in basal cell carcinoma in young women. This increase
      may lead to an exponential increase in the overall occurrence of nonmelanoma skin
      cancers over time as this population ages, which emphasizes the need to focus on
      skin cancer prevention in young adults.

PMID- 16091571
TI  - Angiotensin-converting enzyme insertion/deletion genotype, exercise, and physical
      decline.
AB  - CONTEXT: Physical performance in response to exercise appears to be influenced by
      the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) genotype in
      young adults, but whether this relationship could help explain variation in older
      individuals' response to exercise has not been well studied. OBJECTIVE: To
      determine whether the ACE genotype interacts with significant physical activity
      to affect the incidence of mobility limitation in well-functioning older adults.
      DESIGN, SETTING, AND PARTICIPANTS: The Health Aging and Body Composition (Health
      ABC) Cohort Study, conducted in the metropolitan areas of Memphis, Tenn, and
      Pittsburgh, Pa. A total of 3075 well-functioning community-dwelling adults aged
      70 through 79 years were enrolled from 1997 to 1998 and had a mean of 4.1 years
      of follow-up. MAIN OUTCOME MEASURE: Incident mobility limitation defined as the
      report of difficulty walking a quarter of a mile (0.4 km) or walking up 10 steps
      on 2 consecutive semiannual interviews (n = 1204). RESULTS: Physically active
      participants (those reporting expending > or =1000 kcal/wk in exercise, walking,
      and stair climbing) were less likely to develop mobility limitation regardless of
      genotype. However, activity level interacted significantly with the ACE genotype
      (P = .002). In the inactive group, the ACE genotype was not associated with
      limitation (P = .46). In the active group, those with the II genotype were more
      likely to develop mobility limitation after adjusting for potential confounders
      compared with those with ID/DD genotypes (adjusted rate ratio, 1.45, 95%
      confidence interval, 1.08-1.94). The gene association was especially strong among
      participants reporting weightlifting. Exploration of possible physiological
      correlates revealed that among active participants, those with the II genotype
      had higher percentage of body fat (P = .02) and more intermuscular thigh fat (P =
      .02) but had similar quadriceps strength as those with ID/DD. CONCLUSIONS: Among
      older individuals who exercised, those with the ACE DD or ID genotypes were less
      likely to develop mobility limitation than those with the II genotype. Regardless
      of genotype, individuals who exercised were less likely to develop mobility
      limitation than those who did not exercise.

PMID- 16091572
TI  - Childhood vaccination and nontargeted infectious disease hospitalization.
AB  - CONTEXT: It has been hypothesized that multiple-antigen vaccines, such as measles
      mumps-rubella vaccine, or aggregated vaccine exposure could lead to immune
      dysfunction, resulting in nontargeted infectious diseases as a result of an
      "overload" mechanism. OBJECTIVE: To evaluate the relationship between routinely
      administered childhood vaccines (Haemophilus influenzae type b; diphtheria
      tetanus-inactivated poliovirus; diphtheria-tetanus-acellular pertussis
      inactivated poliovirus; whole-cell pertussis; measles-mumps-rubella; oral
      poliovirus) and hospitalization for nontargeted infectious diseases. DESIGN,
      SETTING, AND PARTICIPANTS: Population-based cohort comprising all children born
      in Denmark from 1990 through 2001 (N = 805 206). Longitudinal information was
      collected on type and number of vaccine doses received and hospitalization with
      infectious diseases, specifically acute upper respiratory tract infection, viral
      and bacterial pneumonia, septicemia, viral central nervous system infection,
      bacterial meningitis, and diarrhea. MAIN OUTCOME MEASURES: Rate ratios for each
      type of infectious disease according to vaccination status. RESULTS: During
      2,900,463 person-years of follow-up, 84,317 cases of infectious disease
      hospitalization were identified. Out of 42 possible associations (6 vaccines and
      7 infectious disease categories), the only adverse association was for
      Haemophilus influenzae type b vaccine and acute upper respiratory tract infection
      (rate ratio, 1.05; 95% confidence interval, 1.01-1.08 comparing vaccinated
      participants with unvaccinated participants). This one adverse association of 42
      possible outcomes was within the limits of what would be expected by chance alone
      and the effect was not temporal or dose-response. When considering aggregated
      vaccine exposure, we found no adverse associations between an increasing number
      of vaccinations and infectious diseases. CONCLUSION: These results do not support
      the hypotheses that multiple-antigen vaccines or aggregated vaccine exposure
      increase the risk of nontargeted infectious disease hospitalization.

PMID- 16091573
TI  - Duration of anticoagulation following venous thromboembolism: a meta-analysis.
AB  - CONTEXT: Patients with venous thromboembolism (VTE) are susceptible to recurrent
      events, but whether prolonging anticoagulation is warranted in patients with VTE
      remains controversial. OBJECTIVE: To review the available evidence and quantify
      the risks and benefits of extending the duration of anticoagulation in patients
      with VTE. DATA SOURCES: PubMed, EMBase Pharmacology, the Cochrane database,
      clinical trial Web sites, and a hand search of reference lists. STUDY SELECTION:
      Included studies were randomized controlled trials with results published from
      1969 through 2004 and evaluating the duration of anticoagulation in patients with
      VTE that measured recurrent VTE. Excluded studies were those enrolling only pure
      populations of high-risk patients. Two independent reviewers assessed each
      article for inclusion and exclusion criteria, with adjudication by a third
      reviewer in cases of disagreement. Fifteen of 67 studies were included in the
      analysis. DATA EXTRACTION: Two independent reviewers performed data extraction
      using a standardized form, with adjudication by the remainder of the
      investigators in cases of disagreement. Data regarding recurrent VTE, major
      bleeding, person-time at risk, and study quality were extracted. DATA SYNTHESIS:
      If patients in the long-term therapy group remained receiving anticoagulation,
      the risk of recurrent VTE with long- vs short-term therapy was reduced (weighted
      incidence rate, 0.020 vs 0.126 events/person-year; rate difference, -0.106 [95%
      confidence interval {CI}, -0.145 to -0.067]; P<.001; pooled incidence rate ratio
      [IRR], 0.21 [95% CI, 0.14 to 0.31]; P<.001). If anticoagulation in the long-term
      therapy group was discontinued, the risk reduction was less pronounced (weighted
      incidence rate, 0.052 vs 0.072 events/person-year; rate difference, -0.020 [95%
      CI, -0.039 to -0.001]; P = .04; pooled IRR, 0.69 [95% CI, 0.53 to 0.91]; P =
      .009). The risk of major bleeding with long- vs short-term therapy was similar
      (weighted incidence rate, 0.011 vs 0.006 events/person-year; rate difference,
      0.005 [95% CI, -0.002 to 0.011]; P = .14; pooled IRR, 1.80 [95% CI, 0.72 to
      4.51]; P = .21). CONCLUSIONS: Patients who receive extended anticoagulation are
      protected from recurrent VTE while receiving long-term therapy. The clinical
      benefit is maintained after anticoagulation is discontinued, but the magnitude of
      the benefit is less pronounced.

PMID- 16091574
TI  - Clinical practice guidelines and quality of care for older patients with multiple
      comorbid diseases: implications for pay for performance.
AB  - CONTEXT: Clinical practice guidelines (CPGs) have been developed to improve the
      quality of health care for many chronic conditions. Pay-for-performance
      initiatives assess physician adherence to interventions that may reflect CPG
      recommendations. OBJECTIVE: To evaluate the applicability of CPGs to the care of
      older individuals with several comorbid diseases. DATA SOURCES: The National
      Health Interview Survey and a nationally representative sample of Medicare
      beneficiaries (to identify the most prevalent chronic diseases in this
      population); the National Guideline Clearinghouse (for locating evidence-based
      CPGs for each chronic disease). STUDY SELECTION: Of the 15 most common chronic
      diseases, we selected hypertension, chronic heart failure, stable angina, atrial
      fibrillation, hypercholesterolemia, diabetes mellitus, osteoarthritis, chronic
      obstructive pulmonary disease, and osteoporosis, which are usually managed in
      primary care, choosing CPGs promulgated by national and international medical
      organizations for each. DATA EXTRACTION: Two investigators independently assessed
      whether each CPG addressed older patients with multiple comorbid diseases, goals
      of treatment, interactions between recommendations, burden to patients and
      caregivers, patient preferences, life expectancy, and quality of life.
      Differences were resolved by consensus. For a hypothetical 79-year-old woman with
      chronic obstructive pulmonary disease, type 2 diabetes, osteoporosis,
      hypertension, and osteoarthritis, we aggregated the recommendations from the
      relevant CPGs. DATA SYNTHESIS: Most CPGs did not modify or discuss the
      applicability of their recommendations for older patients with multiple
      comorbidities. Most also did not comment on burden, short- and long-term goals,
      and the quality of the underlying scientific evidence, nor give guidance for
      incorporating patient preferences into treatment plans. If the relevant CPGs were
      followed, the hypothetical patient would be prescribed 12 medications (costing
      her 406 dollars per month) and a complicated nonpharmacological regimen. Adverse
      interactions between drugs and diseases could result. CONCLUSIONS: This review
      suggests that adhering to current CPGs in caring for an older person with several
      comorbidities may have undesirable effects. Basing standards for quality of care
      and pay for performance on existing CPGs could lead to inappropriate judgment of
      the care provided to older individuals with complex comorbidities and could
      create perverse incentives that emphasize the wrong aspects of care for this
      population and diminish the quality of their care. Developing measures of the
      quality of the care needed by older patients with complex comorbidities is
      critical to improving their care.

PMID- 16091575
TI  - Prognosis and decision making in severe stroke.
AB  - CONTEXT: An increasing number of deaths following severe stroke are due to
      terminal extubations. Variation in withdrawal-of-care practices suggests the
      possibility of unnecessary prolongation of suffering or of unwanted deaths.
      OBJECTIVES: To review the available evidence on prognosis in mechanically
      ventilated stroke patients and to provide an overall framework to optimize
      decision making for clinicians, patients, and families. DATA SOURCES: Search of
      MEDLINE from 1980 through March 2005 for English-language articles addressing
      prognosis in mechanically ventilated stroke patients. From 689 articles
      identified, we selected 17 for further review. We also identified factors that
      influence, and decision-making biases that may result, in overuse or underuse of
      life-sustaining therapies, with a particular emphasis on mechanical ventilation.
      EVIDENCE SYNTHESIS: Overall mortality among mechanically ventilated stroke
      patients is high, with a 30-day death rate approximating 58% (range in
      literature, 46%-75%). Although data are limited, among survivors as many as one
      third may have no or only slight disability, yet many others have severe
      disability. One can further refine prognosis according to knowledge of stroke
      syndromes, early patient characteristics, use of clinical prediction rules, and
      the need for continuing interventions. Factors influencing preferences for life
      sustaining treatments include the severity and pattern of future clinical
      deficits, the probability of these deficits, and the burdens of treatments.
      Decision-making biases that may affect withdrawal-of-treatment decisions include
      erroneous prognostic estimates, inappropriate methods of communicating evidence,
      misunderstanding patient values and expectations, and failing to appreciate the
      extent to which patients can physically and psychologically adapt. CONCLUSIONS:
      Although prognosis among mechanically ventilated stroke patients is generally
      poor, a minority do survive without severe disability. Prognosis can be assessed
      according to clinical presentation and patient characteristics. There is an
      urgent need to better understand the marked variation in the care of these
      patients and to reliably measure and improve the patient-centeredness of such
      decisions.

PMID- 16091576
TI  - HIV testing without consent in critically ill patients.

PMID- 16091577
TI  - Disclosing individual results of clinical research: implications of respect for
      participants.

PMID- 16091578
TI  - Adding value to evidence-based clinical guidelines.

PMID- 16091579
TI  - JAMA patient page. Thrombophlebitis.

PMID- 16091580
TI  - UT-A urea transporter promoter, UT-Aalpha, targets principal cells of the renal
      inner medullary collecting duct.
AB  - The urea transporters, UT-A1 and UT-A3, two members of the UT-A gene family, are
      localized to the terminal portion of the inner medullary collecting duct (IMCD).
      In this manuscript, we demonstrate that 4.2 kb of the 5'-flanking region of the
      UT-A gene (UT-Aalpha promoter) is sufficient to drive the IMCD-specific
      expression of a heterologous reporter gene, beta-galactosidase (beta-Gal), in
      transgenic mice. RT-PCR, immunoblotting, and immunohistochemistry demonstrate
      that within the kidney, transgene expression is confined to the terminal portion
      of the IMCD. Colocalization studies with aquaporin-2 show that expression is
      localized to the principal cells of the IMCD2 and IMCD3 regions. Utilizing beta
      Gal activity assays, we further show that within the kidney, the beta-Gal
      transgene can be regulated by both water restriction and glucocorticoids, similar
      to the regulation of the endogenous UT-A gene. These results demonstrate that 4.2
      kb of the UT-Aalpha promoter is sufficient to drive expression of a heterologous
      reporter gene in a tissue-specific and cell-specific fashion in transgenic mice.

PMID- 16091581
TI  - Renal expression and localization of the facilitative glucose transporters GLUT1
      and GLUT12 in animal models of hypertension and diabetic nephropathy.
AB  - Renal tubular glucose reabsorption is mediated by facilitative glucose
      transporter (GLUT) proteins and energy-dependent sodium glucose luminal
      transporters. Glucose transport in the diabetic kidney is upregulated and has
      been implicated in the pathogenesis of progressive diabetic nephropathy.
      Hyperglycemia, hypertension, and activation of the renin-angiotensin system are
      believed important in the development of the disease. The present study examines
      the renal expression of the facilitative glucose transporters GLUT1 and GLUT12 in
      rat models of diabetic nephropathy. Sprague-Dawley and transgenic (mRen-2)27 rats
      received either streptozotocin-induced diabetes or vehicle. GLUT12 expression and
      localization were determined by immunohistochemistry, immunoblotting, in situ
      hybridization, and confocal immunofluorescence. GLUT1 immunolabeling was detected
      on the basolateral membrane throughout the nephron. GLUT12 was localized to the
      distal tubules and collecting ducts. A significant increase in GLUT12
      immunolabeling was measured in Ren-2 controls and Ren-2 diabetic animals compared
      with Sprague-Dawley controls. GLUT12 expression was higher in Ren-2 diabetic
      compared with Sprague-Dawley diabetic rats. Long-term diabetes resulted in
      significant increases in GLUT1 levels in the renal proximal tubules and
      expression was higher in Ren-2 diabetic than Sprague-Dawley diabetic rats. GLUT12
      protein was localized to the cytoplasm and to the apical membrane of human and
      rat distal tubules and collecting ducts. The apical localization of GLUT12 in the
      distal tubules and collecting ducts suggests that it could contribute to
      additional glucose reabsorption in the late nephron. Levels of both GLUT1 and
      GLUT12 are elevated in animal models of hypertension and diabetic nephropathy.

PMID- 16091582
TI  - Morphological and functional evidence for an important role of the endothelial
      cell glycocalyx in the glomerular barrier.
AB  - In this study, we pursued the somewhat controversial issue whether the
      glycosaminoglycans (GAG) in the endothelial cell glycocalyx are important for
      glomerular size and charge selectivity. In isoflurane-anesthetized mice,
      Intralipid droplets were used as indirect markers of the glomerular endothelial
      cell-surface layer, i.e., the glycocalyx. The mice were given intravenous
      injections of GAG-degrading enzymes, which due to their high molecular weight
      remained and acted intravascularly. Flow-arrested kidneys were fixed and prepared
      for electron microscopy, and the distance between glomerular endothelial cells
      and the luminal Intralipid droplets was measured. The relative frequency of
      Intralipid droplets was calculated for each 50-nm increment zone up to 500 nm
      from the endothelial cell membrane surface as were the mean distances. Glomerular
      size and charge selectivity were estimated from the clearance data for neutral
      Ficolls (molecular radii of 12-72 A), and albumin in isolated kidneys was
      perfused at 8 degrees C. In enzyme-treated animals (hyaluronidase, heparinase,
      and chondroitinase), the relative Intralipid droplet frequency in the zone
      closest to the endothelial cells, i.e., 0-50 nm, was increased approximately 2.5
      times compared with controls. Also, the mean distance between the Intralipid
      droplets and the endothelium was decreased from 176 to 115-122 nm by enzyme
      treatment. These changes were accompanied by an increase in the fractional
      clearance for albumin. In conclusion, both morphological and functional
      measurements suggest the endothelial cell glycocalyx to be an important component
      of the glomerular barrier.

PMID- 16091583
TI  - Regulation of TRPV1 by a novel renally expressed rat TRPV1 splice variant.
AB  - The capsaicin receptor and transient receptor potential channel TRPV1 senses
      heat, protons, and vanilloid agonists in peripheral sensory ganglia. Abundant
      data have suggested the presence of potentially novel splice variants in the
      kidney. We report a novel rat TRPV1 splice variant, TRPV1(VAR), cloned from
      kidney papilla. TRPV1(VAR) cDNA was identified in multiple kidney tissues. Its
      sequence was fully compatible with potential splice donor and acceptor sites in
      the rat TRPV1 gene. TRPV1(VAR) is predicted to encode a truncated form of TRPV1
      consisting of the NH2-terminal 248 residues of TRPV1 (all within the NH2-terminal
      intracellular domain) followed by five nonconsensus amino acids (Arg-Glu-Ala-Met
      Trp) and a stop codon. The variant utilizes the same consensus Kozak sequence as
      canonical TRPV1. A band of the appropriate molecular mass was identified in rat
      kidney papillary (but not medullary) lysates immunoblotted with an antibody
      directed against the NH2 terminus of TRPV1, whereas an antibody recognizing the
      TRPV1 COOH terminus failed to detect it. Upon heterologous expression in HEK 293
      cells, TRPV1(VAR) potentiated the ability of cotransfected TRPV1 to confer
      calcium influx in response to resiniferatoxin. TRPV1(VAR) did not influence
      expression or cell surface localization of cotransfected TRPV1. TRPV1(VAR)
      protein product associated with the NH2 terminus of canonical TRPV1.
      Interestingly, when expressed in the COS-7 epithelial cell line, TRPV1(VAR)
      functioned in a dominant-negative acting capacity, partially blocking TRPV1
      dependent resiniferatoxin responsiveness. We conclude that TRPV1(VAR) is one of
      perhaps several TRPV1 splice variants expressed in rat kidney and that it may
      serve to modulate TRPV1 responsiveness in some tissues.

PMID- 16091584
TI  - Study of androgen receptor functions by genetic models.
AB  - Androgens exert most of their biological activities through binding to the
      androgen receptor (AR). The AR belongs to the nuclear receptor superfamily and
      acts as a ligand-inducible transcriptional factor. AR dysfunction causes a
      diverse range of clinical conditions, such as testicular mutation (Tfm) syndrome,
      prostate cancer, and spinal and bulbar muscular atrophy (SBMA). However, the
      molecular basis of the AR function underlying these AR-related disorders remains
      largely unknown due to the lack of stable genetic models. Here we review recent
      results of our studies into genetic models of the loss of AR function in mice and
      the gain of AR function in Drosophila.

PMID- 16091585
TI  - Dominant portion of thyrotropin-releasing hormone receptor is excluded from lipid
      domains. Detergent-resistant and detergent-sensitive pools of TRH receptor and
      Gqalpha/G11alpha protein.
AB  - Some G protein-coupled receptors might be spacially targetted to discrete domains
      within the plasma membrane. Here we assessed the localization in membrane domains
      of the epitope-tagged, fluorescent version of thyrotropin-releasing hormone
      receptor (VSV-TRH-R-GFP) expressed in HEK293 cells. Our comparison of three
      different methods of cell fractionation (detergent extraction, alkaline
      treatment/sonication and mechanical homogenization) indicated that the dominant
      portion of plasma membrane pool of the receptor was totally solubilized by Triton
      X-100 and its distribution was similar to that of transmembrane plasma membrane
      proteins (glycosylated and non-glycosylated forms of CD147, MHCI, CD29, CD44,
      transmembrane form of CD58, Tapa1 and Na,K-ATPase). As expected, caveolin and GPI
      bound proteins CD55, CD59 and GPI-bound form of CD58 were preferentially
      localized in detergent-resistant membrane domains (DRMs). Trimeric G proteins
      G(q)alpha/G(11)alpha, G(i)alpha1/G(i)alpha2, G(s)alphaL/G(s)alphaS and Gbeta were
      distributed almost equally between detergent-resistant and detergent-solubilized
      pools. In contrast, VSV-TRH-R-GFP, Galpha, Gbeta and caveolin were localized
      massively only in low-density membrane fragments of plasma membranes, which were
      generated by alkaline treatment/sonication or by mechanical homogenization of
      cells. These data indicate that VSV-TRH-R-GFP as well as other transmembrane
      markers of plasma membranes are excluded from TX-100-resistant, caveolin-enriched
      membrane domains. Trimeric G protein G(q)alpha/G(11)alpha occurs in both DRMs and
      in the bulk of plasma membranes, which is totally solubilized by TX-100.

PMID- 16091586
TI  - Catalytic residues and substrate specificity of recombinant human tripeptidyl
      peptidase I (CLN2).
AB  - Tripeptidyl peptidase I (TTP-I), also known as CLN2, a member of the family of
      serine-carboxyl proteinases (S53), plays a crucial role in lysosomal protein
      degradation and a deficiency in this enzyme leads to fatal neurodegenerative
      disease. Recombinant human TPP-I and its mutants were analyzed in order to
      clarify the biochemical role of TPP-I and its mechanism of activity. Ser280,
      Glu77, and Asp81 were identified as the catalytic residues based on mutational
      analyses, inhibition studies, and sequence similarities with other family
      members. TPP-I hydrolyzed most effectively the peptide Ala-Arg-Phe*Nph-Arg-Leu
      (*, cleavage site) (k(cat)/K(m) = 2.94 microM(-1).s(-1)). The k(cat)/K(m) value
      for this substrate was 40 times higher than that for Ala-Ala-Phe-MCA. Coupled
      with other data, these results strongly suggest that the substrate-binding cleft
      of TPP-I is composed of only six subsites (S(3)-S(3)'). TPP-I prefers bulky and
      hydrophobic amino acid residues at the P(1) position and Ala, Arg, or Asp at the
      P(2) position. Hydrophilic interactions at the S(2) subsite are necessary for TPP
      I, and this feature is unique among serine-carboxyl proteinases. TPP-I might have
      evolved from an ancestral gene in order to cleave, in cooperation with
      cathepsins, useless proteins in the lysosomal compartment.

PMID- 16091587
TI  - Repetitive interactions observed in the crystal structure of a collagen-model
      peptide, [(Pro-Pro-Gly)9]3.
AB  - The crystal structure of a collagen-model peptide [(Pro-Pro-Gly)(9)](3) has been
      determined at 1.33 A resolution. Diffraction data were collected at 100 K using
      synchrotron radiation, which led to the first structural study of [(Pro-Pro
      Gly)(n)](3) under cryogenic conditions. The crystals belong to the P2(1) space
      group with cell parameters of a = 25.95, b = 26.56, c = 80.14 Angstroms and beta
      = 90.0 degrees. The overall molecular conformation was consistent with the left
      handed 7/2-helical model with an axial repeat of 20 A for native collagen. A
      total of 332 water molecules were found in an asymmetric unit. Proline residues
      in adjacent triple-helices exhibited three types of hydrophobic interactions.
      Furthermore, three types of hydrogen-bonding networks mediated by water molecules
      were observed between adjacent triple-helices. These hydrophobic interactions and
      hydrogen-bonding networks occurred at intervals of 20 Angstroms along the c-axis
      based on the previous sub-cell structures [(Pro-Pro-Gly)(n)](3) (n = 9, 10),
      which were also seen in the full-cell structure of [(Pro-Pro-Gly)(10)](3). Five
      proline residues at the Y position in the X-Y-Gly triplet were found in a down
      puckering conformation, this being inconsistent with the recently proposed
      propensity-based hypothesis. These proline residues were forced to adopt opposing
      puckering because of the prevailing hydrophobic interaction between triple
      helices compared with the Pro:Pro stacking interaction within a triple-helix.

PMID- 16091588
TI  - Molecular character of the recombinant antitumor lectin from the edible mushroom
      Agrocybe aegerita.
AB  - The lectin from Agrocybe aegerita (AAL) has been found to possess potent tumor
      suppressing function and tumor cell apoptosis-inducing activity. In this paper,
      we report the full sequence, the active expression of the gene encoding AAL at a
      high level and bioassay of the binding property with lactose, apoptosis-inducing
      activity and DNase activity of recombinant AAL (rAAL). The results reveal that
      AAL is a member of the galectin family and the dimeric form is the active unit
      for the functional performance. The rAAL showed comparable tumor cell apoptosis
      inducing activity with the wild AAL but no DNase activity at all. The molecular
      characters revealed by this study are significant for the in-depth investigation
      of the functional mechanism of this interesting protein.

PMID- 16091589
TI  - Characteristics of apoptosis in HCT116 colon cancer cells induced by deoxycholic
      acid.
AB  - Hydrophobic bile acids induce apoptosis in both colon cancer cells and
      hepatocytes. The mechanism by which colon cancer cells respond to bile acids is
      thought to be different from that of hepatocytes. Therefore, we investigated the
      characteristics of apoptosis in colon cancer cell line HCT116. Hydrophobic bile
      acids, i.e., deoxycholic acid (DCA), and chenodeoxycholic acid, induced apoptosis
      in HCT116 cells. Apoptotic indications were detectable at as early as 30 min and
      the extent increased in time- and concentration-dependent manners. SDS and a
      hydrophilic bile acid, cholic acid, did not induce apoptosis even at cytotoxic
      concentrations. Pretreatment with cycloheximide failed to inhibit apoptosis,
      suggesting that protein synthesis is not involved in the apoptotic response.
      Release of cytochrome c from mitochondria and activation of caspase-9 were
      detectable after 5 and 10 min, respectively, whereas remarkable activation of Bid
      was not detected. Ursodeoxycholic acid (UDCA) protected HCT116 cells from DCA
      induced apoptosis but a preincubation period of > or =5 h was required.
      Nevertheless, UDCA did not inhibit cytochrome c release from mitochondria. Our
      results indicate that hydrophobic bile acids induce apoptosis in HCT116 cells by
      releasing cytochrome c from mitochondria via an undefined but specific mechanism,
      and that UDCA protects HCT116 cells by acting downstream of cytochrome c release.

PMID- 16091590
TI  - Characterization of a thermostable enzyme with
      phosphomannomutase/phosphoglucomutase activities from the hyperthermophilic
      archaeon Pyrococcus horikoshii OT3.
AB  - The phosphomannomutase/phosphoglucomutase (PMM/PGM) enzyme catalyzes reversibly
      the intra-molecular phosphoryl interconverting reaction of mannose-6-phosphate
      and mannose-1-phosphate or glucose-6-phosphate and glucose-1-phosphate. Glucose-6
      phosphate and glucose-1-phosphate are known to be utilized for energy metabolism
      and cell surface construction, respectively. PMM/PGM has been isolated from many
      microorganisms. By performing similarity searches using existing PMM/PGM
      sequences, the homologous ORFs PH0923 and PH1210 were identified from the genomic
      data of Pyrococcus horikoshii OT3. Since PH0923 appears to be part of an operon
      consisting of four carbohydrate metabolic enzymes, PH0923 was selected as the
      first target for the investigation of PMM/PGM activity in P. horikoshii OT3. The
      coding region of PH0923 was cloned and the purified recombinant protein was
      utilized for an examination of its biochemical properties. The enzyme retained
      half its initial activity after treatment at 95 degrees C for 90 min. Detailed
      analyses of activities showed that this protein is capable of utilizing a variety
      of metal ions that are not utilized by previously characterized PMM/PGM proteins.
      A mutated protein with an alanine residue replacing the active site serine
      residue indicated that this residue plays an important but non-essential role in
      PMM/PGM activity.

PMID- 16091591
TI  - Expression of erythropoietin receptor-like molecule in Xenopus laevis and
      erythrocytopenia upon administration of its recombinant soluble form.
AB  - The regulation of hematopoiesis in non-mammalian vertebrates is poorly
      understood. This is partly because the structures and effects of most
      hematopoietic regulators have not been identified. As a first step towards
      studies on the key mechanism of hematopoietic regulation among phyla as well as
      the diversity of organisms, we have focused on amphibian hematopoiesis. A cDNA
      sharing the highest degree of homology with mammalian erythropoietin (EPO)
      receptors, tentatively named xlEPOR, was cloned from a cDNA library of Xenopus
      laevis immature erythrocytes. The comparative identities of the deduced entire
      amino acid sequence to mammalian EPO receptors were quite low, although
      functional domains indispensable for erythropoietic activities were found in the
      molecule. Northern analysis revealed that xlEPOR were expressed in peripheral
      blood cells. In the peripheral blood of phenylhydrazine-treated adult Xenopus,
      immature erythrocytes expressing xlEPOR were identified by in situ hybridization
      and immunostaining with polyclonal antibodies to xlEPOR. To confirm the
      biological functions of this molecule, the extracellular domain of xlEPOR (i.e.,
      soluble xlEPOR) was administered to adult Xenopus by consecutive intracardiac
      injection. The peripheral erythrocyte counts were decreased gradually; meanwhile,
      immature erythrocytes appeared in the circulation, demonstrating that xlEPOR
      plays a significant physiological role in erythropoiesis in Xenopus laevis.

PMID- 16091592
TI  - The interaction between PSD-95 and Ca2+/calmodulin is enhanced by PDZ-binding
      proteins.
AB  - In this study, we evaluate the interaction between the postsynaptic scaffolding
      protein, PSD-95, and calmodulin. Surface plasmon resonance spectroscopy was used
      to characterize the binding of PSD-95 to calmodulin that had been immobilized on
      a sensor chip. Additionally, soluble calmodulin was found to inhibit the binding
      of PSD-95 to immobilized calmodulin. The HOOK region of PSD-95, which is located
      between the src homology 3 domain and the guanylate kinase-like domain, was
      determined to be involved in the binding of PSD-95 to calmodulin. We also found
      that C-terminal peptides from proteins such as CRIPT and the N-methyl-d-aspartate
      receptor NR2B subunit, which associate with the PDZ domain of PSD-95, enhanced
      the affinity of PSD-95 for calmodulin. The binding of ligands to the PDZ domain
      may change the conformation of PSD-95 and affect the interaction between PSD-95
      and calmodulin.

PMID- 16091593
TI  - Expression of functional Streptomyces coelicolor H+-pyrophosphatase and
      characterization of its molecular properties.
AB  - H(+)-translocating pyrophosphatases (H(+)-PPases) are proton pumps that are found
      in many organisms, including plants, bacteria and protozoa. Streptomyces
      coelicolor is a soil bacterium that produces several useful antibiotics. Here we
      investigated the properties of the H(+)-PPase of S. coelicolor by expressing a
      synthetic DNA encoding the amino-acid sequence of the H(+)-PPase in Escherichia
      coli. The H(+)-PPase from E. coli membranes was active at a relatively high pH,
      stable up to 50 degrees C, and sensitive to N-ethylmaleimide, N,N'
      dicyclohexylcarbodiimide and acylspermidine. Enzyme activity increased by 60% in
      the presence of 120 mM K(+), which was less than the stimulation observed with
      plant vacuolar H(+)-PPases (type I). Substitutions of Lys-507 in the Gly-Gln-x-x
      (Ala/Lys)-Ala motif, which is thought to determine the K(+) requirement of H(+)
      PPases, did not alter its K(+) dependence, suggesting that other residues control
      this feature of the S. coelicolor enzyme. The H(+)-PPase was detected during
      early growth and was present mainly on the plasma membrane and to a lesser extent
      on intracellular membranous structures.

PMID- 16091594
TI  - Expression and molecular characterization of spherical particles derived from the
      genome of the hyperthermophilic euryarchaeote Pyrococcus furiosus.
AB  - Spherical particles (SPs) of approximately 30 nm in diameter were found in the
      hyperthermophilic archaeon Pyrococcus furiosus. The SPs contained no nucleic acid
      and were composed of a single 39-kDa protein. The amino acid sequences of the
      amino-terminal and internal fragments were identical to portions of the deduced
      amino acid sequence of the putative 38.7-kDa protein encoded by the genome of P.
      furiosus, suggesting that the protein was expressed from the genome of P.
      furiosus. This possibility was confirmed by the observation that the 38.7-kDa
      protein expressed in Escherichia coli reacted specifically with the antibody
      against purified SPs, and it also formed SPs similar to those found in P.
      furiosus. Of the 345 amino acid residues in the 38.7-kDa protein, the amino
      terminal 100 amino acids exhibited strong homology to putative proteins from
      other species of Pyrococcus, while the remaining 245 carboxy-terminal residues
      were not significantly homologous to putative proteins from other members of
      archaea. Thus, the carboxy-terminal region might be the product of a foreign gene
      that was incorporated relatively recently into the genome of P. furiosus.

PMID- 16091595
TI  - Mitochondrial ATP synthase residue betaarginine-408, which interacts with the
      inhibitory site of regulatory protein IF1, is essential for the function of the
      enzyme.
AB  - Mitochondrial ATP synthase (F(1)F(0)-ATPase) is regulated by an intrinsic ATPase
      inhibitor protein, IF(1). We previously found that six residues of the yeast
      IF(1) (Phe17, Arg20, Glu21, Arg22, Glu25, and Phe28) form an ATPase inhibitory
      site [Ichikawa, N. and Ogura, C. (2003) J. Bioenerg. Biomembr. 35, 399-407]. In
      the crystal structure of the F(1)/IF(1) complex [Cabezon, E. et al. (2003) Nat.
      Struct. Biol. 10, 744-750], the core residues of the inhibitory site interact
      with Arg408, Arg412 and Glu454 of the beta-subunit of F(1). In the present study,
      we examined the roles of the three beta residues by means of site-directed
      mutagenesis. A total of six yeast mutants were constructed: R408I, R408T, R412I,
      R412T, E454Q, and E454V. The betaArg412 and betaGlu454 mutants (R412I, R412T,
      E454Q, and E454V) could grow on a nonfermentable lactate medium, but the
      betaArg408 mutants (R408I and R408T) could not. The ATPase activity of isolated
      mitochondria was decreased in R412I, R412T, E454Q, and E454V mutant cells, and
      undetectable in R408I and R408T cells. The subunits of F(1) (alpha, beta, and
      gamma) were detected in mitochondria from each mutant on immunoblotting, and the
      F(1)F(0) complex was isolated from them. These results indicate that betaArg408
      is essential not for assembly of the F(1)F(0) complex but for the catalytic
      activity of the enzyme. In the crystal structure of F(1), betaArg408 binds to
      alphaGlu399 in the alpha(DP)/beta(DP) pair and seems to be important for
      formation of the closed alpha(DP)/beta(DP) conformation. IF(1) seems to disrupt
      this alpha(DP)Glu399/beta(DP)Arg408 interaction by binding to beta(DP)Arg408, and
      to interfere with the change from the open alpha(DP)/beta(DP) conformation to the
      closed conformation that is required for catalysis by F(1)F(0)-ATPase.

PMID- 16091596
TI  - Characterization of wheat germ agglutinin ligand on soluble glycoproteins in
      Caenorhabditis elegans.
AB  - Some mutants of Caenorhabditis elegans show altered patterns of ectopic binding
      with wheat germ agglutinin (WGA). Some of these mutants also have defects of
      morphogenesis and movement during development. To clarify the structures of WGA
      ligands in C. elegans that may be involved in developmental events, we have
      analyzed glycan structures capable of binding WGA. We isolated glycoproteins from
      wild-type C. elegans by WGA-affinity chromatography, and analyzed their glycan
      structures by a combination of hydrazine degradation and fluorescent labeling.
      The glycoproteins had oligomannose-type and complex-type N-glycans that included
      agalacto-biantenna and agalacto-tetraantenna glycans. Although the complex-type
      glycans carried beta-GlcNAc residues at their non-reducing ends, they did not
      bind to the WGA-agarose-resin. Thus, it was suggested that these N-glycans were
      not responsible for WGA-binding of the isolated glycoproteins. Hydrazinolysis of
      the glycoproteins also released a considerable amount of GalNAc monosaccharide.
      It was surmised that N-acetylgalactosamine was derived from mucin-type O-glycans
      with the Tn-antigen structure (GalNAcalpha1-O-Ser/Thr). WGA-blotting assay of
      neoglycoproteins revealed that a cluster of Tn-antigens was a good ligand for
      WGA. These results suggested that the WGA-ligand in C. elegans is a cluster of
      alpha-GalNAc monosaccharides linked to mucin-like glycoprotein(s). The
      observations reported in this paper emphasize the possible significance of mucin
      type O-glycans in the development of a multicellular organism.

PMID- 16091597
TI  - Environmental implications of adopting a dominant factor approach to salinity
      management.
AB  - Additive or multiplicative models of crop response on which salinity management
      theory have been developed may lead to an erroneous perception regarding
      compensative interaction among salinity and other growth factors. We present
      results from studies of biomass production and transpiration of corn (Zea mays L.
      cv. Jubilee), melon (Cucumis melo L. subsp. melo cv. Galia), tomato (Lycopersicon
      esculentum Mill. cv. 5656), onion (Allium cepa L. cv. HA 944), and date palms
      (Phoenix dactylifera L. cv. Medjool) under salinity combined with water or
      nitrate (growth promoters) or with boron (growth inhibitor). The measured crop
      responses were to the more severe stress rather than to combinations of the
      individual effects of the various stresses. Consequences of shifting management
      of saline water to a dominant factor approach include reduction of environmental
      contamination and conservation of water resources.

PMID- 16091598
TI  - Manipulation of dietary protein and nonstarch polysaccharide to control swine
      manure emissions.
AB  - Odor and greenhouse gas (GHG) emissions from stored pig (Sus scrofa) manure were
      monitored for response to changes in the crude protein level (168 or 139 g kg(
      1), as-fed basis) and nonstarch polysaccharide (NSP) content [i.e., control, or
      modified with beet pulp (Beta vulgaris L.), cornstarch, or xylanase] of diets fed
      to pigs in a production setting. Each diet was fed to one of eight pens of pigs
      according to a 2 x 4, full-factorial design, replicated over three time blocks
      with different groups of animals and random assignment of diets. Manure from each
      treatment was characterized and stored in a separate, ventilated, 200-L vessel.
      Repeated measurements of odor, carbon dioxide (CO2), methane (CH4), and nitrous
      oxide (N2O) emissions from the vessels were taken every two weeks for eight
      weeks. Manure from high-protein diets had higher sulfur concentration and pH (P <
      or = 0.05). High-NSP (beet pulp) diets resulted in lower manure nitrogen and
      ammonia concentrations and pH (P < or = 0.05). Odor level and hedonic tone of
      exhaust air from the storage vessel headspaces were unaffected by the dietary
      treatments. Mean CO2 and CH4 emissions (1400 and 42 g d(-1) m(-3) manure,
      respectively) increased with lower dietary protein (P < or = 0.05). The addition
      of xylanase to high-protein diets caused a decrease in manure CO2 emissions, but
      an increase when added to low-protein diets (P < or = 0.05). Nitrous oxide
      emissions were negligible. Contrary to other studies, these results do not
      support the use of dietary protein reduction to reduce emissions from stored
      swine manure.

PMID- 16091599
TI  - Nitrogen oxide and methane emissions under varying tillage and fertilizer
      management.
AB  - Comprehensive assessment of the total greenhouse gas (GHG) budget of reduced
      tillage agricultural systems must consider emissions of nitrous oxide (N2O) and
      methane (CH4), each of which have higher global warming potentials than carbon
      dioxide (CO2). Tillage intensity may also impact nitric oxide (NO) emissions,
      which can have various environmental and agronomic impacts. In 2003 and 2004, we
      used chambers to measure N2O, CH4, and NO fluxes from plots that had been managed
      under differing tillage intensity since 1991. The effect of tillage on non-CO2
      GHG emissions varied, in both magnitude and direction, depending on fertilizer
      practices. Emissions of N2O following broadcast urea (BU) application were higher
      under no till (NT) and conservation tillage (CsT) compared to conventional
      tillage (CT). In contrast, following anhydrous ammonia (AA) injection, N2O
      emissions were higher under CT and CsT compared to NT. Emissions following
      surface urea ammonium nitrate (UAN) application did not vary with tillage. Total
      growing season non-CO2 GHG emissions were equivalent to CO2 emissions of 0.15 to
      1.9 Mg CO2 ha(-1) yr(-1) or 0.04 to 0.53 Mg soil-C ha(-1) yr(-1). Emissions of
      N2O from AA-amended plots were two to four times greater than UAN- and BU-amended
      plots. Total NO + N2O losses in the UAN treatment were approximately 50% lower
      than AA and BU. This study demonstrates that N2O emissions can represent a
      substantial component of the total GHG budget of reduced tillage systems, and
      that interactions between fertilizer and tillage practices can be important in
      controlling non-CO2 GHG emissions.

PMID- 16091600
TI  - Predicting inter-taxa differences in plant uptake of cesium-134/137.
AB  - For (134/137)Cs, and many other soil contaminants, research into transfer to
      plants has focused on particular crops and phytoremediation candidates, producing
      uptake data for a small proportion of all plant taxa. Despite the significance of
      differences in uptake between plant taxa, the capacity of soil-to-plant transfer
      models to predict them is currently confined to those taxa for which data exist,
      there being no method to predict uptake by other taxa. We used residual maximum
      likelihood (REML) analysis on data from experiments (including 89 plant taxa from
      China plus 32 phytoremediation candidates) together with data from the
      literature, to construct a database of relative (134/137)Cs concentrations in 273
      plant taxa. The REML (134/137)Cs concentrations in plants are not normally
      distributed but significantly clustered. Analysis of variance (ANOVA), coded with
      a recent ordinal phylogeny for flowering plants, showed that plant taxa do not
      behave independently for (134/137)Cs concentration because 42 and 15% of inter
      taxa differences are associated with phylogeny above the species and ordinal
      level, respectively. In general, Eudicots, and especially the Caryophyllales,
      Asterales, and Brassicales, have high (134/137)Cs concentrations, while the
      Fabales and Magnoliids, in particular Poales, have low (134/137)Cs
      concentrations. Plants of the stress-tolerant ruderal (S-R) growth strategy sensu
      Grime have, in general, high concentrations of Cs, while those of the competitive
      (C) and generalist (C-S-R) strategies have low concentrations, although these
      effects are less pronounced than those of phylogeny. Plant phylogeny and growth
      strategy might thus be used to predict a significant portion of inter-taxa
      differences in plant uptake of (134/137)Cs.

PMID- 16091601
TI  - Simulation of phytoremediation of a TNT-contaminated soil using the CTSPAC model.
AB  - Knowledge of water movement in the plant-xylem system and contaminant
      bioavailability in the soil environment is crucial to evaluate the success of
      phytoremediation practices. This study investigated the removal of 2,4,6
      trinitrotoluene (TNT) from a contaminated sandy soil by a single poplar (Populus
      fastigiata) tree through the examinations of temporal variations of xylem water
      potential, root water uptake, and soil TNT bioavailability. A mathematical model,
      CTSPAC (Coupled Transport of water, heat, and solutes in the Soil-Plant
      Atmosphere Continuum), was modified for the purpose of this study. The model was
      calibrated using laboratory measurements before its application. Our simulations
      show that the xylem water potential was high in the roots and low in the leaves
      with a potential head difference of 3.55 cm H2O, which created a driving force
      for water flow and chemical transport upward from the roots through the stem to
      the leaves. The daily average root water uptake rate was 25 cm3 h(-1) when an
      equilibrium condition was reached after 24 h. Our simulations further reveal that
      no TNT was found in the stem and leaves and only about 1% of total TNT mass was
      observed in the roots due to the rapid biodegradation and transformation of TNT
      into its daughter products. About 13% of the soil TNT was removed by the poplar
      tree, resulting mainly from root uptake since TNT is a recalcitrant compound. In
      general, the soil TNT bioavailability decreased with time due to the depletion of
      soil solution TNT by the poplar tree. A constant bioavailability (i.e., 3.1 x 10(
      6)) was obtained in 14 d in which the soil TNT concentration was about 10 mg L(
      1). Our study suggests that CTSPAC is a useful model to simulate phytoremediation
      of TNT-contaminated sites.

PMID- 16091602
TI  - Uptake and transport of radioactive nickel and cadmium into three vegetables
      after wet aerial contamination.
AB  - Knowledge of radionuclide or trace element retention and translocation to plants
      following an aerial contamination event, for example, sprinkling with
      contaminated water, is necessary for the evaluation of human exposure through
      consumption of contaminated vegetables. The fate of 63Ni and 109Cd in all plant
      parts of three different vegetables after wet deposition on leaves or on fruits
      was studied. Lettuce (Lactuca sativa L.), radish (Raphanus sativus L.), and bean
      (Phaseolus vulgaris L.) grown under controlled conditions in a growth chamber
      were contaminated with 63Ni and 109Cd either on leaves, by means of two different
      contamination methods (a single early contamination and a repetitive one), or on
      bean husks (third contamination method: a single contamination at a late stage).
      Spiked and nonspiked organs were harvested at maturity and radionuclide contents
      were measured. The fraction retained was on average 56% of the initially
      administered doses of 63Ni and 87% of 109Cd. The leaf-to-other organ
      translocation factor was considerably higher for 63Ni (on average 43% of retained
      radioactivity) than for 109Cd (8%). Nickel-63 migrated throughout the whole plant
      following foliar contamination, and mainly toward young leaves, seeds in
      formation, and sink organs, whereas 109Cd migrated to a much lesser extent and
      only to the organs that were closest to the spiked one, and not at all into
      fruit. After a fruit contamination event, both radionuclides were translocated
      into the seeds of spiked fruits. Radionuclide retention and translocation were
      not affected by plant species, but principally by the type of organ contaminated.

PMID- 16091603
TI  - Molecular composition of leaves and stems of genetically modified Bt and near
      isogenic non-Bt maize--characterization of lignin patterns.
AB  - Transformation of crops, including maize (Zea mays L.), with the cry1Ab gene from
      Bacillus thuringiensis to combat lepidopteran pests results in pleiotropic
      effects regarding lignin biosynthesis. Lignin patterns in stems and leaves of two
      genetically modified Bt-maize varieties (Novelis T and Valmont T) were studied
      along with their non-Bt near-isolines (Nobilis and Prelude, respectively).
      Molecular-level based thermochemolysis using tetramethylammonium hydroxide (TMAH)
      in combination with gas chromatography-mass spectrometry (GC-MS) was used to
      quantitate the total lignin contents and to identify monomeric lignin subunits
      including p-hydroxyphenyl (P), guaiacyl (G), and syringyl (S) moieties. The
      results were supplemented and confirmed by cupric oxide oxidation. The stems of
      the transgenic lines had higher concentrations of total lignin than the
      respective isogenic lines: Valmont T/Prelude by 18% and Novelis T/Nobilis by 28%.
      In contrast, differences in the total lignin concentration of leaves between the
      transgenic and the respective near-isogenic lines were marginal. There were
      significant modifications in the ratio of p-hydroxyphenyl/guaiacyl/syringyl
      molecular marker units of stem lignin between transgenic and isogenic lines. The
      guaiacyl units (in particular the G18 marker) accounted chiefly for the higher
      total lignin contents in the transgenic lines. The leaf lignin patterns did not
      show significant differences in molecular markers between isogenic and transgenic
      lines. TMAH-induced thermochemolysis--conducted in both the on-line and off-line
      modes--provided detailed information on the molecular composition of lignin, thus
      proving superior to the established "wet chemistry" methods of lignin
      determination.

PMID- 16091604
TI  - Metals distribution and interactions in tissues of shrews (Sorex spp.) from
      copper- and zinc-contaminated areas in Poland.
AB  - To assess the risk from heavy metal accumulation to insectivorous species exposed
      to different pollutants, shrews [Sorex araneus (Linnaeus 1758) and Sorex minutus
      (Linnaeus 1766)] were collected in the Olkuski Ore Region (OOR; a Zn and Cd
      smelter area), Legnicko-Glogowski Copper Mine Region (LGCR; a copper ore-mining
      area), and Bialowieza Forest (BF; a control area). A few sites were chosen in
      each region and a total of 57 animals were collected from them. The liver and
      kidneys were dissected from the animals, dried, and digested in a 4:1 mixture of
      HNO3 (nitric acid) and HClO4 (perchloric acid). Cadmium, lead, zinc, copper, and
      iron were determined in the samples by flame or flameless atomic absorption
      spectrometry. The interactions between toxic and essential metals were calculated
      for each tissue. The data showed that accumulation of metals by insectivores is
      high; shrews accumulated much higher amounts of cadmium and lead than bank voles,
      studied by other researchers, from the same areas. The expected high tissue
      accumulation of copper at LGCR and zinc at OOR was not seen, but the levels of
      both elements were higher in the tissues of shrews from OOR than from LGCR. The
      lowest copper concentrations were in the tissues of shrews from BF. The highest
      cadmium and lead concentrations were found in the tissues of shrews from OOR.
      Some significant correlations were found between the tissue concentrations of
      xenobiotic and essential metals (e.g., between cadmium and zinc and between lead
      and iron).

PMID- 16091605
TI  - Cadmium solubility and sorption in a long-term sludge-amended arable soil.
AB  - Cadmium solubility and sorption in an arable clay loam soil that had received
      sewage sludge for 41 years were compared to an unsludged control in batch
      studies. Soil pH dominated Cd sorption, explaining >92% of the variation in Kd
      values in both treatments. At any pH, Cd sorption was apparently slightly but
      significantly (p < 0.05) smaller in the sludge-amended soil compared to the
      control, even though the organic carbon content was 70% larger and the ammonium
      oxalate-extractable iron content was roughly doubled. Correction for dissolved
      organic carbon (DOC) complexation with the speciation model WHAM reduced the
      difference in sorption between treatments, but the sludged soil still had
      significantly smaller Kd values (p < 0.01). Batch equilibrations without addition
      of Cd showed that there was no significant difference in the solubility of
      "native" cadmium (defined as EDTA-extractable Cd) in sludged and control soils.
      The reason for the lack of increase in Cd sorption in the sludge-amended soil has
      not been established, but it may be due to competition for sorption sites on
      humic compounds with sludge-derived Fe and trace metals such as zinc. The fact
      that the pyrophosphate-extractable (i.e., organically associated) iron content
      was seven times larger in the sludged soil provides some supporting evidence for
      this hypothesis.

PMID- 16091606
TI  - Reduction of copper(II) by iron(II).
AB  - Laboratory and field investigations have clearly demonstrated the important role
      of reduced iron (Fe(II)) in reductive transformations of first-row transition
      metal species. However, interactions of Fe(II) and copper (Cu) are not clearly
      understood. This study examined the reduction of Cu(II) by Fe(II) in stirred
      batch experiments at pH 5.2 and 5.5 as influenced by chloride (Cl-) concentration
      (0.002-0.1 M), initial metal concentration (0.1-9.1 mM), and reaction time (1-60
      min) under anoxic conditions. Reduction of Cu(II) to Cu(I) by dissolved Fe(II)
      was rapid under all experimental conditions and the stability of the products
      explains the driving force for the redox reaction. Under conditions of low [Cl-]
      and high initial metal concentration, >40% of total Cu and Fe were removed from
      solution after 1 min, which accompanied formation of a brownish-red precipitate.
      X-ray diffraction (XRD) patterns of the precipitates revealed the presence of
      cuprite (Cu2O), a Cu(I) mineral, based on d-spacings located at 0.248, 0.215,
      0.151, and 0.129 nm. Fourier transform infrared (FTIR) spectroscopy corroborated
      XRD data for the presence of Cu2O, with features located at 518, 625, and 698 cm(
      1). Increasing [Cl-] stabilized the dissolved Cu(I) product against Cu2O
      precipitation and resulted in more Fe precipitated from solution (relative to Cu)
      that appears to be present as poorly crystalline lepidocrocite (gamma-FeOOH).
      This process may be important in anoxic soil environments, where dissolved Fe(II)
      levels can accumulate.

PMID- 16091607
TI  - Agricultural practices influence flow regimes of headwater streams in western
      Iowa.
AB  - Agricultural tillage influences runoff and infiltration, but consequent effects
      on watershed hydrology are poorly documented. This study evaluated 25 yr (1971
      1995) hydrologic records from four first-order watersheds in Iowa's loess hills.
      Two watersheds were under conventional tillage and two were under conservation
      (ridge) tillage, one of which was terraced. All four watersheds grew corn (Zea
      mays L.) every year. Flow-frequency statistics and autoregressive modeling were
      used to determine how conservation treatments influenced stream hydrology. The
      autoregressive modeling characterized variations in discharge, baseflow, and
      runoff at multi-year, annual, and shorter time scales. The ridge-tilled watershed
      (nonterraced) had 47% less runoff and 36% more baseflow than the conventional
      watershed of similar landform and slope. Recovery of baseflow after drought was
      quicker in the conservation watersheds, as evidenced by 365-d moving average
      plots, and 67% greater baseflow during the driest 2 yr. The two conventional
      watersheds were similar, except the steeper watershed discharged more runoff and
      baseflow during short (<30 d), wet periods. Significant multi-year and annual
      cycles occurred in all variables. Under ridge-till, seasonal (annual-cycle)
      variations in baseflow had greater amplitude, showing the seasonality of
      subsurface contaminant movement could increase under conservation practices.
      However, deviations from the modeled cycles of baseflow were also more persistent
      under conservation practices, indicating baseflow was more stable. Indeed, flow
      frequency curves showed wet-weather discharge decreased and dry-weather discharge
      increased under conservation practices. Although mean discharge increased in the
      conservation watersheds, variance and skewness of daily values were smaller.
      Ridge tillage with or without terraces increased stream discharge but reduced its
      variability.

PMID- 16091608
TI  - Fire and grazing effects on wind erosion, soil water content, and soil
      temperature.
AB  - Selective grazing of burned patches can be intense if animal distribution is not
      controlled and may compound the independent effects of fire and grazing on soil
      characteristics. Our objectives were to quantify the effects of patch burning and
      grazing on wind erosion, soil water content, and soil temperature in sand
      sagebrush (Artemisia filifolia Torr.) mixed prairie. We selected 24, 4-ha plots
      near Woodward, OK. Four plots were burned during autumn (mid-November) and four
      during spring (mid-April), and four served as nonburned controls for each of two
      years. Cattle were given unrestricted access (April-September) to burned patches
      (<2% of pastures) and utilization was about 78%. Wind erosion, soil water
      content, and soil temperature were measured monthly. Wind erosion varied by burn,
      year, and sampling height. Wind erosion was about 2 to 48 times greater on autumn
      burned plots than nonburned plots during the dormant period (December-April).
      Growing-season (April-August) erosion was greatest during spring. Erosion of
      spring-burned sites was double that of nonburned sites both years. Growing-season
      erosion from autumn-burned sites was similar to nonburned sites except for one
      year with a dry April-May. Soil water content was unaffected by patch burn
      treatments. Soils of burned plots were 1 to 3 degrees C warmer than those of
      nonburned plots, based on mid-day measurements. Lower water holding and deep
      percolation capacity of sandy soils probably moderated effects on soil water
      content and soil temperature. Despite poor growing conditions following fire and
      heavy selective grazing of burned patches, no blowouts or drifts were observed.

PMID- 16091609
TI  - Degradation of methyl isothiocyanate and chloropicrin in forest nursery soils.
AB  - Recent studies have observed enhanced degradation of methyl isothiocyanate (MITC)
      from repeated fumigation in agricultural soils. Little is known about fumigant
      degradation in forest and nursery soils. This study was conducted to determine
      degradation rates of MITC and chloropicrin (CP) in two forest soils and the
      impacts of nursery management on degradation of MITC and CP. The half-life values
      of MITC and CP were evaluated in the laboratory under isothermal conditions (22
      +/- 2 degrees C). Three rates representing 0.5x, 1x, and 2x field application
      rates for each fumigant were used in laboratory incubations. Effect of microbial
      degradation was determined by conducting incubations with both fresh and
      sterilized soils. Soil moisture effects were also studied. There was no
      difference in MITC or CP degradation between fumigated and nonfumigated forest
      nursery soils. Soil sterilization and high soil moisture content (15% by wt.)
      reduced MITC and CP degradation. The degradation rates of MITC and CP varied with
      factors such as nursery history, fumigant application rates, and freshness of
      tested soils.

PMID- 16091610
TI  - Effects of commercial diazinon and imidacloprid on microbial urease activity in
      soil and sod.
AB  - Diazinon [O,O-diethyl O-2-isopropyl-6-methyl(pyrimidine-4-yl) phosphorothioate]
      and imidacloprid [1-(1-[6-chloro-3-pyridinyl]methyl)-N-nitro-2-imidazolidinimine]
      are applied to lawns for insect control simultaneously with nitrogenous
      fertilizers such as urea, but their potential effect on urease activity and
      nitrogen availability in turfgrass management has not been evaluated. Urease
      activity in enzyme assays, washed cell assays, and soil slurries was examined as
      a function of insecticide concentration. Intact cores from field sites were used
      to assess the effect of insecticide application on urease activity in creeping
      bentgrass (Agrostis palustris Huds.) and bluegrass (Poa pratensis L.) sod.
      Bacterial urease from Bacillus pasteurii and plant urease from jack bean
      [Canavalia ensiformis (L.) DC.] were unaffected by the insecticides. Both
      insecticides inhibited the growth of Proteus vulgaris, a urease-producing
      bacterium, but only diazinon significantly reduced urease activity in washed
      cells; neither insecticide inhibited urease activity in sonicated cells. Neither
      diazinon nor imidacloprid inhibited urease activity in Woolper soil (fine, mixed,
      mesic Typic Argiudoll) slurries, but diazinon slightly inhibited urease activity
      in Maury soil (fine, mixed, semiactive, mesic Typic Paleudalf) slurries.
      Imidacloprid had no effect on urease activity in creeping bentgrass or bluegrass
      sod at up to 10 times the commercial application rate. Diazinon briefly, but
      significantly, reduced urease activity in bluegrass sod. Co-application of
      imidacloprid and urea appears to be benign with respect to urease activity in
      soil and sod. Diazinon, in contrast, appears to have a significant, short-term,
      inhibitory effect on the microbial urease-producing community, but that effect
      depends on soil type.

PMID- 16091611
TI  - Polycyclic aromatic hydrocarbons (PAHs) in soils of the Moscow Region-
      concentrations, temporal trends, and small-scale distribution.
AB  - The knowledge of the environmental fate of polycyclic aromatic hydrocarbons
      (PAHs) is restricted to few climatic regions of the world almost excluding the
      Taiga. Our objectives were to (i) separate anthropogenic from background
      contributions to PAH concentrations and (ii) determine temporal trends in PAH
      concentrations during the last century including the change in distribution of
      PAHs in interior and exterior portions of aggregates in soils of the Moscow
      region. Along a southeast-bound transect from Moscow (windward in winter) and at
      a background location northeast of Moscow (leeward in winter), seven topsoil
      samples were collected in 1910-1954 and 35 in 1998-2003. We fractionated the
      soils in interior and exterior portions of aggregates > 10 mm and remaining soil
      without aggregates. The sum of 21 PAHs (sigma21PAHs) concentrations in recent
      bulk soil ranged from 59 to 1350 ng g(-1). The concentrations of all PAHs were
      lower outside than in Moscow. The range of the concentrations of the sigma21PAHs
      in archived soil samples (159-1280 ng g(-1)) was similar as in recent soils. In
      most recent and archived samples, naphthalene and phenanthrene, were most
      abundant. The concentrations of low-molecular-weight PAHs decreased during the
      last century at most sites; those of high-molecular-weight compounds increased.
      The sigma21PAHs concentrations were accumulated in the exterior of aggregates
      (109%) and depleted in the interior (95%) relative to the concentration in bulk
      soil (defined as 100%), which was similar to that in the soil without aggregates
      (99%). The differences between aggregate interior and exterior did not change
      during the last century. The dominance of naphthalene and phenanthrene is typical
      of remote regions. The urban influence on PAH concentrations in the last century
      was small.

PMID- 16091612
TI  - Transport and metabolic fate of sewage particles in a recipient stream.
AB  - Although the implementation of wastewater treatment plants (WWTP) has
      dramatically increased the quality of surface waters in urbanized areas, WWTPs
      can still discharge noticeable amounts of solutes and particles to recipient
      streams. Although the fate of WWTP nutrients has received considerable attention,
      transport and in-stream transformation of sewage-derived particulate organic
      matter (SDPOM) have not. To investigate the transport and transformation of SDPOM
      in recipient streams, we experimentally injected fluorescently labeled SDPOM into
      a headwater stream and tracked its downstream fate at baseflow. Most SDPOM
      disappeared from the streamwater within a 160-m long reach with an average
      deposition velocity of 0.14 mm s(-1). We further coupled hydrometric measurements
      of specific water fluxes through the streambed interface with a mixing model to
      estimate streambed oxygen removal, and found significantly higher oxygen removal
      in the deposition (0.75 g O2 m(-2) d(-1)) than in the downstream post-deposition
      (0.36 g O2 m(-2) d(-1)) subreach. Contrary to our expectations, we did not detect
      any apparent effect of SDPOM deposition on streambed clogging. Our results show
      the capacity of a recipient stream to retain SDPOM and to reduce its downstream
      export, and thus contribute to a better understanding of ecosystem services of
      human-altered streams.

PMID- 16091614
TI  - Temporal variability in physical speciation of metals during a winter rain-on
      snow event.
AB  - Particulate matter in urban rivers transports a significant fraction of
      pollutants, changes rapidly during storm events, and is difficult to
      characterize. In this study, the physical speciation of trace metals and organic
      C in an urban river and upstream headwaters site in Torrington, CT, were measured
      during a winter rain-on-snow event. In addition, a selective fractionation
      scheme, using membrane and tangential-flow ultrafiltration methods to separate
      suspended particulate matter into sand, silt, clay, and colloid fractions, was
      evaluated based on the appropriateness of the chosen size categories. During peak
      runoff at the urban river site, total-recoverable concentrations of the metals Cu
      and Pb increased 6- and 13-fold to 16.9 and 9.5 microg L(-1), respectively,
      compared with baseflow concentrations. Concentrations of Cu and Pb reached only
      0.9 and 0.86 microg L(-1) at the headwaters site. For the measured storm event,
      the majority of metals were transported by the urban river in association with
      coarse silt (20-80 microm particle diam.) during peak runoff. During peak runoff
      at the urban site, organic C associated with the large colloid fraction (0.1-1.0
      microm) increased from 5% (at baseflow) to 54% of the total C in transport,
      whereas dissolved organic C and that associated with smaller colloids decreased
      from 91.5% (at baseflow) to 41% of the total. Other elements that were monitored
      as part of the study were Na, K, Ca, Mg, Fe, Mn, Al, Cd, Cl-, NO3(-), and SO4(2
      ). The chosen fractionation scheme was useful to characterize pollutant transport
      during this event, but further testing should be undertaken to determine the most
      appropriate size range categories, and to ensure that the sizes measured are
      comparable to those used in other studies.

PMID- 16091613
TI  - The effect of flow path and mixing layer on phosphorus release: physical
      mechanisms and temperature effects.
AB  - Soil phosphorus (P) concentrations typically are greater in surface soils
      compared with subsurface soils. Surface soils have a greater chance to interact
      with runoff leading to P transport to streams. The thin surface layer where P
      concentrates is referred to as the mixing layer denoting where water and
      chemicals mix during transport. The objective of this study was to evaluate the
      effect of hydrologic flow paths on soluble reactive phosphorus (SRP) loss at two
      temperatures. Laboratory flumes were built to simulate infiltration, return flow,
      saturation excess, and interflow, and subsequent interaction with the mixing
      layer. The sandy loam soil in the flumes was kept at saturation throughout all
      experiments, so that biochemical effects were normalized. Flow through the flumes
      was maintained at 3.6 mm/h for 24 to 99 h (at 6 and 25 degrees C) with water
      entering and exiting the flumes at different ports (to simulate different flow
      paths) or as low intensity rainfall. Experiments were performed with and without
      an artificially created P-enriched surface layer (5 mm thick, total P increased
      from 1010 mg/kg in the original soil to 2310 mg/kg by addition of dissolved
      phosphate). Results indicated that (i) SRP release was greater in soil with a
      mixing layer than in soil without a mixing layer; (ii) SRP release was greater
      during experiments at 25 degrees C than at 6 degrees C; (iii) at 25 degrees C,
      SRP release was greatest when water traversed the mixing layer in the upward
      direction (i.e., in return flow), and by flow parallel to the mixing layer (i.e.,
      surface runoff); and (iv) at 6 degrees C, SRP release in subsurface flow
      following rainfall was slightly greater than in return flow and infiltration. Our
      results confirmed the presence of a variable, temperature-dependent desorption
      process when runoff water interacted with the mixing layer. Our findings have
      important implications for how different water flow paths in and over the soil
      interact with P in the soil, and what the ultimate concentration will be in
      runoff and interflow.

PMID- 16091615
TI  - Corn residue level and manure application timing effects on phosphorus losses in
      runoff.
AB  - Growing interest in corn (Zea mays L.) silage utilization on Wisconsin dairy
      farms may have implications for nutrient losses from agricultural lands.
      Increasing the silage cutting height will increase residue cover and could reduce
      off-site migration of sediments and associated constituents compared with
      conventional silage harvesting. We examined the effects of residue level and
      manure application timing on phosphorus (P) losses in runoff from no-till corn.
      Treatments included conventional corn grain (G) and silage (SL; 10- to 15-cm
      cutting height) and nonconventional, high-cut (60-65 cm) silage (SH) subjected to
      different manure application regimes: no manure (N) or surface application in
      fall (F) or spring (S). Simulated rainfall (76 mm h(-1); 1 h) was applied in
      spring and fall for two years (2002-2003), runoff from 2.0- x 1.5-m plots was
      collected, and subsamples were analyzed for dissolved reactive phosphorus (DRP),
      total phosphorus (TP), and P mass distribution in four particle size classes.
      Total P and DRP loads were inversely related to percent residue cover, but both
      TP and DRP concentrations were unaffected by residue level. Manure application
      increased DRP concentrations in spring runoff by two to five times but did not
      significantly affect DRP loads, since higher concentrations were offset by lower
      runoff volumes. Spring manure application reduced TP loads in spring runoff by 77
      to 90% compared with plots receiving no manure, with the extent of reductions
      being greatest at the lower residue levels (<24%). The TP concentration in
      sediments increased as particle size decreased. Manure application increased the
      TP concentration of the 0- to 2-microm fraction by 79 to 125%, but elevated the 2
      to 10- and 10- to 50-microm fractions to a lesser extent. Recent manure
      additions were most influential in enriching transported sediments with P. By
      itself, higher residue cover achieved by high-cutting silage was often
      insufficient to lower P losses; however, the combination of manure application
      and higher residue levels significantly reduced P losses from corn fields
      harvested for silage.

PMID- 16091616
TI  - Runoff phosphorus losses from surface-applied biosolids.
AB  - Runoff losses of dissolved and particulate phosphorus (P) may occur when rainfall
      interacts with manures and biosolids spread on the soil surface. This study
      compared P levels in runoff losses from soils amended with several P sources,
      including 10 different biosolids and dairy manure (untreated and treated with Fe
      or Al salts). Simulated rainfall (71 mm h(-1)) was applied until 30 min of runoff
      was collected from soil boxes (100 x 20 x 5 cm) to which the P sources were
      surfaced applied. Materials were applied to achieve a common plant available
      nitrogen (PAN) rate of 134 kg PAN ha(-1), resulting in total P loading rates from
      122 (dairy manure) to 555 (Syracuse N-Viro biosolids) kg P ha(-1). Two biosolids
      produced via biological phosphorus removal (BPR) wastewater treatment resulted in
      the highest total dissolved phosphorus (13-21.5 mg TDP L(-1)) and total
      phosphorus (18-27.5 mg TP L(-1)) concentrations in runoff, followed by untreated
      dairy manure that had statistically (p = 0.05) higher TDP (8.5 mg L(-1)) and TP
      (10.9 mg L(-1)) than seven of the eight other biosolids. The TDP and TP in runoff
      from six biosolids did not differ significantly from unamended control (0.03 mg
      TDP L(-1); 0.95 mg TP L(-1)). Highest runoff TDP was associated with P sources
      low in Al and Fe. Amending dairy manure with Al and Fe salts at 1:1 metal-to-P
      molar ratio reduced runoff TP to control levels. Runoff TDP and TP were not
      positively correlated to TP application rate unless modified by a weighting
      factor reflecting the relative solubility of the P source. This suggests site
      assessment indices should account for the differential solubility of the applied
      P source to accurately predict the risk of P loss from the wide variety of
      biosolids materials routinely land applied.

PMID- 16091617
TI  - Soil characteristics and phosphorus level effect on phosphorus loss in runoff.
AB  - The loss of phosphorus (P) in runoff from agricultural soils may accelerate
      eutrophication in lakes and streams as well as degrade surface water quality.
      Limited soil specific data exist on the relationship between runoff P and soil P.
      This study investigated the relationship between runoff dissolved reactive
      phosphorus (DRP) and soil P for three Oklahoma benchmark soils: Richfield (fine,
      smectitic, mesic Aridic Argiustoll), Dennis (fine, mixed, active, thermic Aquic
      Argiudoll), and Kirkland (fine, mixed, superactive, thermic Udertic Paleustoll)
      series. These soils were selected to represent the most important agricultural
      soils in Oklahoma across three major land resource areas. Surface soil (0-15 cm)
      was collected from three designated locations, treated with diammonium phosphate
      (18-46-0) to establish a wide range of water-soluble phosphorus (WSP) (3.15-230
      mg kg(-1)) and Mehlich-3 phosphorus (M3P) (27.8-925 mg kg(-1)). Amended soils
      were allowed to reach a steady state 210 d before simulated rainfall (75 mm h(
      1)). Runoff was collected for 30 min from bare soil boxes (1.0 x 0.42 m and 5%
      slope) and analyzed for DRP and total P. Soil samples collected immediately
      before rainfall simulation were analyzed for the following: M3P, WSP, ammonium
      oxalate P saturation index (PSI(ox)), water-soluble phosphorus saturation index
      (PSI(WSP)), and phosphorus saturation index calculated from M3P and phosphorus
      sorption maxima (P(sat)). The DRP in runoff was highly related (p < 0.001) to M3P
      for individual soil series (r2 > 0.92). Highly significant relationships (p <
      0.001) were found between runoff DRP and soil WSP for the individual soil series
      (r2 > 0.88). Highly significant relationships (p < 0.001) existed between DRP and
      different P saturation indexes. Significant differences (p < 0.05) among the
      slopes of the regressions for the DRP-M3P, DRP-WSP, DRP-PSI(ox), DRP-PSI(WSP),
      and DRP-P(sat) relationships indicate that the relationships are soil specific
      and phosphorus management decisions should consider soil characteristics.

PMID- 16091618
TI  - Quantifying the impact of regular cutting on vegetative buffer efficacy for
      nitrogen-15 sequestration.
AB  - This study used the stable 15N isotope to quantitatively examine the effects of
      cutting on vegetative buffer uptake of NO3(-)-N based on the theory that regular
      cutting would increase N demand and sequestration by encouraging new plant
      growth. During the summer of 2002, 10 buffer plots were established within a
      flood-irrigated pasture. In 2003, 15N-labeled KNO3 was applied to the pasture
      area at a rate of 5 kg N ha(-1) and 99.7 atom % 15N. One-half of the buffer plots
      were trimmed monthly. In the buffers, the cutting effect was not significant in
      the first few weeks following 15N application, with both the cut and uncut
      buffers sequestering 15N. Over the irrigation season, however, cut buffers
      sequestered 2.3 times the 15N of uncut buffers, corresponding to an increase in
      aboveground biomass following cutting. Cutting and removing vegetation allowed
      the standing biomass to take advantage of soil 15N as it was released by
      microbial mineralization. In contrast, the uncut buffers showed very little
      change in 15N sequestration or biomass, suggesting senescence and a corresponding
      decrease in N demand. Overall, cutting significantly improved 15N attenuation
      from both surface and subsurface water. However, the effect was temporally
      related, and only became significant 21 to 42 d after 15N application. The
      dominant influence on runoff water quality from irrigated pasture remains
      irrigation rate, as reducing the rate by 75% relative to the typical rate
      resulted in a 50% decrease in total runoff losses and a sevenfold decrease in 15N
      concentration.

PMID- 16091619
TI  - Degradation of potassium formate in the unsaturated zone of a sandy aquifer.
AB  - This paper presents results from a lysimeter experiment on the fate of potassium
      formate, an alternative deicing agent. The experiment was performed through the
      winter and spring to identify any thermal sensitivity in the transport and
      biodegradation of formate in the lysimeter. Ninety-eight percent of the total
      quantity of formate applied was degraded while percolating through the 1.7-m
      thick unsaturated sand layer within the lysimeter. Concomitantly, the bicarbonate
      concentration of the percolating water increased. The low concentrations of
      nitrogen (0.02 mg L(-1)) and phosphorous (<0.002 mg L(-1)) in the percolated
      water, however, potentially limited microbial activity. During the study period,
      99% of the applied potassium was retained in the lysimeter, and the ion exchange
      between the potassium and a variety of monovalent and divalent ions was assumed
      to be responsible for the leaching of barium, calcium, magnesium, and sodium from
      the soil material. Except for manganese, the concentrations of the studied metals
      in the percolated water did not exceed the threshold values set for drinking
      water by the Council of the European Union. By contrast, the application of
      potassium formate had a detrimental effect on the vegetation on the lysimeter. To
      conclude, formate was effectively degraded in the sandy lysimeter and its
      application did not cause major undesirable changes in the quality of the
      percolating water. Further research at field scale is, however, needed for
      instance on the biodegradation of potassium formate and on its impacts on
      roadside vegetation.

PMID- 16091620
TI  - Long-term effects of sustained beef feedlot manure application on soil nutrients,
      corn silage yield, and nutrient uptake.
AB  - A field study was initiated in 1992 to investigate the long-term impacts of beef
      feedlot manure application (composted and uncomposted) on nutrient accumulation
      and movement in soil, corn silage yield, and nutrient uptake. Two application
      strategies were compared: providing the annual crop nitrogen (N) requirement (N
      based rate) or crop phosphorus (P) removal (P-based rate), as well as a
      comparison to inorganic fertilizer. Additionally, effects of a winter cover crop
      were evaluated. Irrigated corn (Zea mays L.) was produced annually from 1993
      through 2002. Average silage yield and crop nutrient removal were highest with N
      based manure treatments, intermediate with P-based manure treatments, and least
      with inorganic N fertilizer. Use of a winter cover crop resulted in silage yield
      reductions in four of ten years, most likely due to soil moisture depletion in
      the spring by the cover crop. However, the cover crop did significantly reduce
      NO3-N accumulation in the shallow vadose zone, particularly in latter years of
      the study. The composted manure N-based treatment resulted in significantly
      greater soil profile NO3-N concentration and higher soil P concentration near the
      soil surface. The accounting procedure used to calculate N-based treatment
      application rates resulted in acceptable soil profile NO3-N concentrations over
      the short term. While repeated annual manure application to supply the total crop
      N requirement may be acceptable for this soil for several years, sustained
      application over many years carries the risk of unacceptable soil P
      concentrations.

PMID- 16091621
TI  - Amendment effects on soil test phosphorus.
AB  - Applications of animal manures have increased soil test P values in many parts of
      the USA and thus increased the risk that soil P will be transferred to surface
      water and decrease water quality. To continue farming these areas, landowners
      need tools to reduce the risk of P losses. A field experiment was conducted near
      Kurten, TX, on a Zulch fine sandy loam (thermic Udertic Paleustalfs) with Bray-1
      P values exceeding 3000 mg P kg(-1) soil (dry wt.) in the A(p) horizon to
      evaluate the effectiveness of soil amendments for reducing soil test P values.
      Soils were amended annually from 1999 to 2001 with 1.5 and 5.0 Mg gypsum ha(-1),
      1.4 Mg alum ha(-1), or 24.4 Mg ha(-1) of waste paper product high in Al alone or
      in combination with 1.5 Mg gypsum ha(-1) and/or 1.4 Mg alum ha(-1). These
      treatments supplied a maximum of 225 and 1163 kg ha(-1) yr(-1) of Al and Ca,
      respectively. Soil Bray-1 P and dissolved reactive P levels were monitored from
      1999 to 2004. None of the soil amendment treatments affected Bray-1 P values.
      Only annual additions of 5.0 Mg gypsum ha(-1) from 1999 to 2001 significantly
      reduced soil dissolved reactive P. Dissolved reactive P levels reached minimal
      levels after two applications of 5.0 Mg gypsum ha(-1) but increased in 2003 and
      2004. These results indicate that soil dissolved reactive P levels can be reduced
      if sufficient amounts of gypsum were added to supply Ca in amounts similar to the
      soil test P values.

PMID- 16091622
TI  - Soil properties affecting wheat yields following drilling-fluid application.
AB  - Oil and gas drilling operations use drilling fluids (mud) to lubricate the drill
      bit and stem, transport formation cuttings to the surface, and seal off porous
      geologic formations. Following completion of the well, waste drilling fluid is
      often applied to cropland. We studied potential changes in soil compaction as
      indicated by cone penetration resistance, pH, electrical conductivity (EC(e)),
      sodium adsorption ratio (SAR), extractable soil and total straw and grain trace
      metal and nutrient concentrations, and winter wheat (Triticum aestivum L. 'TAM
      107') grain yield following water-based, bentonitic drilling-fluid application (0
      94 Mg ha(-1)) to field test plots. Three methods of application (normal, splash
      plate, and spreader-bar) were used to study compaction effects. We measured
      increasing SAR, EC(e), and pH with drilling-fluid rates, but not to levels
      detrimental to crop production. Field measurements revealed significantly higher
      compaction within areas affected by truck travel, but also not enough to affect
      crop yield. In three of four site years, neither drilling-fluid rate nor
      application method affected grain yield. Extractions representing plant
      availability and plant analyses results indicated that drilling fluid did not
      significantly increase most trace elements or nutrient concentrations. These
      results support land application of water-based bentonitic drilling fluids as an
      acceptable practice on well-drained soils using controlled rates.

PMID- 16091623
TI  - Broiler litter as a micronutrient source for cotton: concentrations in plant
      parts.
AB  - Analytically, poultry litter contains nearly all essential micronutrients but the
      extent of phytoavailability of these nutrients and whether cotton (Gossypium
      hirsutum L.) and other crop plants can receive adequate amounts of these
      nutrients from litter is not fully known. The objective of this research was to
      determine whether cotton receives sufficient amounts of Fe, Cu, Mn, and Zn from
      litter and estimate the efficiency of cotton in extracting these metal nutrients
      from litter in the absence of any other source of the micronutrients. The
      greenhouse research used plastic pots filled with approximately 11 kg of a 2:1
      (v/v) sand to vermiculite growing mix. Cotton (cv. Stoneville 474) was grown in
      the pots fertilized with broiler litter at rates of 30, 60, 90, or 120 g pot(-1)
      in a factorial combination with four supplemental nutrient solution (NS)
      treatments. The nutrient solutions consisted of full Hoagland's nutrient solution
      (NS-full); a solution of the macronutrients N, P, K, Ca, and Mg (NS-macro); a
      solution of the micronutrients Fe, Zn, Mn, Cu, B, and Mo (NS-micro); and water
      (NS-none). Based on tissue nutrient analysis, a one-time broiler litter
      application supplied adequate amounts of Fe, Cu, and Mn to bring the
      concentration of these nutrients in upper leaves within published sufficiency
      ranges. Zinc, with <17 mg kg(-1) concentration in the upper leaves, was the only
      micronutrient below the established sufficiency range regardless of the rate of
      applied litter. Cotton extracted Fe and Mn more efficiently than Cu or Zn,
      removing as much as 8.8% of Fe and 7.2% of Mn supplied by 30 g litter pot(-1). In
      contrast, the extraction efficiency was 1.7% for Cu and 1.9% for Zn. Roots
      accumulated 58% of the total absorbed Fe and 64% of Cu, and leaves accumulated
      32% of the Fe and only 13% of the Cu supplied by litter. In contrast, only 16% of
      the total absorbed Mn and 23% of Zn accumulated in roots while leaves accumulated
      64% of the total Mn and 37% of Zn. These results demonstrate that broiler litter
      is a valuable source of the metal nutrients supplying Fe, Cu, and Mn in full and
      Zn in part, but a very large fraction of the litter-supplied metal nutrients
      remained in the growing mix.

PMID- 16091624
TI  - 14-3-3 proteins: a number of functions for a numbered protein.
AB  - Many signal transduction events are orchestrated by specific interactions of
      proteins mediated through discrete phosphopeptide-binding motifs. Although
      several phosphospecific-binding domains are now known, 14-3-3s were the first
      proteins recognized to specifically bind a discrete phosphoserine or
      phosphothreonine motif. The 14-3-3 proteins are a family of ubiquitously
      expressed, exclusively eukaryotic proteins with an astonishingly large number of
      binding partners. Consequently, 14-3-3s modulate an enormous and diverse group of
      cellular processes. The effects of 14-3-3 proteins on their targets can be
      broadly defined using three categories: (i) conformational change; (ii) physical
      occlusion of sequence-specific or structural protein features; and (iii)
      scaffolding. This review will describe the current state of knowledge on 14-3-3
      proteins, highlighting several important advances, and will attempt to provide a
      framework by which 14-3-3 functions can be understood.

PMID- 16091625
TI  - Histone deacetylases as transcriptional activators? Role reversal in inducible
      gene regulation.
AB  - Histone deacetylation enzymes have often been associated with the suppression of
      eukaryotic gene transcription. In contrast, recent studies of inducible gene
      regulation indicate that protein deacetylation can also be required as a
      transcriptional activation signal. The concept of protein deacetylation as a
      requirement for transcription activation seems to contradict earlier conclusions
      about the function of deacetylation in gene suppression. However, in the context
      of a more global interpretation, these opposing effects of deacetylation imply
      its dynamic role in the overall control of gene expression. The exact requirement
      for deacetylation differs among promoters, depending on their specific
      architecture and regulation scenario.

PMID- 16091626
TI  - Direct detection of methylation in genomic DNA.
AB  - The identification of methylated sites on bacterial genomic DNA would be a useful
      tool to study the major roles of DNA methylation in prokaryotes: distinction of
      self and nonself DNA, direction of post-replicative mismatch repair, control of
      DNA replication and cell cycle, and regulation of gene expression. Three types of
      methylated nucleobases are known: N6-methyladenine, 5-methylcytosine and N4
      methylcytosine. The aim of this study was to develop a method to detect all three
      types of DNA methylation in complete genomic DNA. It was previously shown that N6
      methyladenine and 5-methylcytosine in plasmid and viral DNA can be detected by
      intersequence trace comparison of methylated and unmethylated DNA. We extended
      this method to include N4-methylcytosine detection in both in vitro and in vivo
      methylated DNA. Furthermore, application of intersequence trace comparison was
      extended to bacterial genomic DNA. Finally, we present evidence that
      intrasequence comparison suffices to detect methylated sites in genomic DNA. In
      conclusion, we present a method to detect all three natural types of DNA
      methylation in bacterial genomic DNA. This provides the possibility to define the
      complete methylome of any prokaryote.

PMID- 16091627
TI  - Headloop suppression PCR and its application to selective amplification of
      methylated DNA sequences.
AB  - Selective amplification in PCR is principally determined by the sequence of the
      primers and the temperature of the annealing step. We have developed a new PCR
      technique for distinguishing related sequences in which additional selectivity is
      dependent on sequences within the amplicon. A 5' extension is included in one (or
      both) primer(s) that corresponds to sequences within one of the related
      amplicons. After copying and incorporation into the PCR product this sequence is
      then able to loop back, anneal to the internal sequences and prime to form a
      hairpin structure-this structure is then refractory to further amplification.
      Thus, amplification of sequences containing a perfect match to the 5' extension
      is suppressed while amplification of sequences containing mismatches or lacking
      the sequence is unaffected. We have applied Headloop PCR to DNA that had been
      bisulphite-treated for the selective amplification of methylated sequences of the
      human GSTP1 gene in the presence of up to a 10(5)-fold excess of unmethylated
      sequences. Headloop PCR has a potential for clinical application in the detection
      of differently methylated DNAs following bisulphite treatment as well as for
      selective amplification of sequence variants or mutants in the presence of an
      excess of closely related DNA sequences.

PMID- 16091628
TI  - Novel DNA-binding properties of the RNA-binding protein TIAR.
AB  - TIA-1 related protein binds avidly to uridine-rich elements in mRNA and pre-mRNAs
      of a wide range of genes, including interleukin (IL)-8 and vascular endothelial
      growth factor (VEGF). The protein has diverse regulatory roles, which in part
      depend on the locus of binding within the transcript, including translational
      control, splicing and apoptosis. Here, we observed selective and potent
      inhibition of TIAR-RNP complex formation with IL-8 and VEGF 3'-untranslated
      regions (3'-UTRs) using thymidine-rich deoxyoligonucleotide (ODN) sequences
      derived from the VEFG 3'-UTR. We show by ultraviolet crosslinking and
      electrophoretic mobility shift assays that TIAR can bind directly to single
      stranded, thymidine-rich ODNs but not to double-stranded ODNs containing the same
      sequence. TIAR had a nearly 6-fold greater affinity for DNA than RNA (K(d)app =
      1.6x10(-9) M versus 9.4 x 10(-9) M). Truncation of TIAR indicated that the high
      affinity DNA-binding site overlaps with the RNA-binding site involving RNA
      recognition motif 2 (RRM2). However, RRM1 alone could also bind to DNA. Finally,
      we show that TIAR can be displaced from single-stranded DNA by active
      transcription through the binding site. These results provide a potential
      mechanism by which TIAR can shuttle between RNA and DNA ligands.

PMID- 16091629
TI  - Evidence for rolling circle replication of tandem genes in Drosophila.
AB  - Extrachromosomal circular DNA (eccDNA) is one characteristic of the plasticity of
      the eukaryotic genome. It is found in various organisms and contains sequences
      derived primarily from repetitive chromosomal DNA. Using 2D gel electrophoresis,
      we have previously detected eccDNA composed of chromosomal tandem repeats
      throughout the life cycle of Drosophila. Here, we report for the first time
      evidence suggesting the occurrence of rolling circle replication of eccDNA in
      Drosophila. We show, on 2D gels, specific structures that can be enriched by
      benzoylated naphthoylated DEAE-cellulose chromatography and were identified in
      other systems as rolling circle intermediates (RCIs). These RCIs are homologous
      to histone genes, Stellate and Suppressor of Stellate, which are all organized in
      the chromosomes as tandem repeats. RCIs are detected throughout the life cycle of
      Drosophila and in cultured fly cells. These structures are found regardless of
      the expression of the replicated gene or of its chromosomal copy number.

PMID- 16091630
TI  - siRNA-mediated off-target gene silencing triggered by a 7 nt complementation.
AB  - A growing body of evidence suggests that siRNA could generate off-target effects
      through different mechanisms. However, the full impact of off-target gene
      regulation on phenotypic induction and accordingly on data interpretation in the
      context of large-scale siRNA library screen has not been reported. Here we report
      on off-target gene silencing effects observed in a large-scale knockdown
      experiment designed to identify novel regulators of the HIF-1 pathway. All of the
      three 'top hits' from our screen have been demonstrated to result from off-target
      gene silencing. Two of the three 'siRNA hits' were found to directly trigger down
      regulation of hif-1alpha mRNA through a 7 nt motif, AGGCAGT, that is present in
      both the hif-1alpha mRNA and the siRNAs. Further analysis revealed that the
      generation of off-target gene silencing via this 7 nt motif depends on the
      characteristics of the target mRNA, including the sequence context surrounding
      the complementary region, the position of the complementary region in the mRNA
      and the copy number of the complementary region. Interestingly, the off-target
      siRNA against hif-1alpha was also shown to trigger mRNA degradation with high
      probability of other genes that possess multiple copies of the AGGCAGT motif in
      the 3'-untranslated region. Lessons learned from this study will be a valuable
      asset to aid in designing siRNAs with more stringent target selectivity and
      improving 'hits-follow-up' strategies for future large-scale knockdown
      experiments.

PMID- 16091632
TI  - [Intensive medical treatment of patients with atherosclerosis].

PMID- 16091631
TI  - Telomere structure and shortening in telomerase-deficient Trypanosoma brucei.
AB  - Telomerase consists of a reverse transcriptase (TERT) and an RNA that contains a
      template for telomere-repeat extension. Telomerase is required to prevent
      telomere erosion and its activity or lack thereof is important for tumorigenesis
      and ageing. Telomerase has been identified in numerous organisms but it has not
      been studied in kinetoplastid protozoa. Trypanosoma brucei, the causative agent
      of African sleeping sickness, evades the host immune response by frequently
      changing its variant surface glycoprotein (VSG). The single expressed VSG is
      transcribed from one of approximately 20 subtelomeric 'Expression Sites', but the
      role telomeres might play in regulating VSG transcription and switching is
      unknown. We identified and sequenced the T.brucei TERT gene. Deleting TERT
      resulted in progressive telomere shortening of 3-6 bp per generation. In other
      organisms, the rate of telomere shortening is proportional to the length of the
      terminal 3' single-strand overhang. In T.brucei, G-overhangs were undetectable
      (<30 nt) by in-gel hybridization. The rate of telomere shortening therefore,
      agrees with the predicted shortening due to the end replication problem, and is
      consistent with our observation that G-overhangs are short. Trypanosomes whose
      telomere length can be manipulated provide a new tool to investigate the role of
      telomeres in antigenic variation.

PMID- 16091633
TI  - [Possibilities of combined quantitative determination of myocardial and coronary
      reserves].

PMID- 16091634
TI  - [Predictive role of exercise tests in development of restenosis in patients after
      coronary stent implantation].
AB  - Bicycle exercise tests were carried out in 2 weeks -- 9 months after successful
      stent implantation in 1463 patients. Result of exercise test was positive in 472
      and negative -- in 991 patients. At control angiography which was performed
      within 1 week after exercise test binary in-stent restenosis >50% was found in
      326 of 1463 patients. Sensitivity, specificity, predictive value of positive and
      negative results of exercise test for the presence of restenosis were 85, 83, 59
      and 5%, respectively.

PMID- 16091635
TI  - [Anti-ischemic efficacy of combination of trimetazidine with enalapril in
      patients with stable effort angina and metabolic syndrome].
AB  - Efficacy of combination of trimetazidine (60 mg/day) and enalapril in patients
      with stable effort angina and metabolic syndrome was assessed in a randomized
      placebo controlled study of 64 patients. Anti-ischemic activity of trimetazidine
      was found to be significant. It was most pronounced in patients with abnormal 24
      hour blood pressure index, waist/hip circumference ratio >1.0 at the background
      of satisfactory clinical and laboratory compensation of type 2 diabetes.

PMID- 16091636
TI  - [Antioxidative defense in patients with acute coronary syndrome and concomitant
      type 2 diabetes and its modification by lisinopril].
AB  - AIM: To study antioxidative defense in patients with acute coronary syndrome
      (ACS) and concomitant type 2 diabetes and its modification by lisinopril.
      MATERIAL AND METHODS: Activity of glutathione reductase and myeloperoxidase in
      neutrophils, catalase and superoxide dismutase in blood was measured in 94
      patients with ACS (including 35 with diabetes) and the patients were followed up
      for 1 year. RESULTS: Number of coronary events during observation was
      significantly higher in patients with diabetes. At baseline these patients had
      significantly lower catalase activity which was associated with elevated blood
      glucose, circulating immune complexes, creatinine, and proteinuria. Baseline
      catalase activity was the lowest in diabetic patients with events (reinfarction
      or death) during follow-up. The latter patients had highest levels of blood
      creatinine and proteinuria, and most pronounced left ventricular systolic
      dysfunction. The use of lisinopril during initial hospitalization was associated
      with elevation of catalase activity, lowering of creatinine and elimination of
      proteinuria.

PMID- 16091637
TI  - [Positron emission tomography in assessment of myocardial metabolism in patients
      with dilated cardiomyopathy and left bundle brunch block].

PMID- 16091638
TI  - [Changes of activity of the endothelial system in experimental heart failure].
AB  - Despite obvious participation of endothelins in pathogenesis of heart failure
      therapeutic approaches to the use of endothelin receptor antagonists remain to be
      elucidated. Experimental heart failure caused by prolonged infusion of
      norepinephrine is associated with diminished endothelin induced coronary
      constricting effect of stimulation of ET(A) receptors and inversion of coronary
      dilating effect of stimulation of these receptors. The latter effect is mediated
      by smooth muscle ET(B)-receptors and is indicative of functional derangement of
      vascular control by endothelial cells. The use of selective ET(A)-antagonist is
      effective on early stages of heart failure while on later stages administration
      of nonselective ET(AB)-antagonist produces more pronounced effect.

PMID- 16091639
TI  - [Depressive disorders in general medical practice in KOMPAS study: outlook of a
      cardiologist].

PMID- 16091640
TI  - [Arterial hypertension and its relation to hereditary burden (family history) in
      male population of Novosibirsk (WHO MONICA Program)].

PMID- 16091641
TI  - [Diagnostic value of circadian variability of blood pressure and cardiac rhythm
      for assessment of clinical-functional status of patients with hypertension].

PMID- 16091642
TI  - [Assessment of adaptational reactions of the organism in patients with normal and
      abnormal sinus node function during ortho-clinostatic stress test].

PMID- 16091643
TI  - [WHO Program "Register of Acute Myocardial Infarction": 25-year (1977-2001)
      epidemiological study of myocardial infarction in Russia].

PMID- 16091644
TI  - [The possible role of circulating multipotent stem cells in development of
      atherosclerosis].

PMID- 16091645
TI  - [Dynamic coronary artery stenosis in survivors of myocardial infarction and
      methods of its detection].

PMID- 16091646
TI  - [First line combined antihypertensive therapy as strategy of successful control
      of hypertension].

PMID- 16091647
TI  - [Relationships between changes of coronary blood flow, energy metabolism of the
      myocardium, and hyperinsulinemia in patients with ischemic heart disease].
AB  - The paper reviews current data on relationships between coronary blood flow,
      hemodynamics, and myocardial energy metabolism during phenomena of stunned and
      hibernating myocardium in patients with ischemic heart disease. These data has
      been obtained with various modern techniques including positron emission
      tomography with (18)F-flourodeoxyglucose, (11)C-palmitate and (11)C-acetate.
      Possible association of remodeling of cardiac energetic metabolism under
      conditions of chronic ischemia and hyperinsulinemia in patients at various stages
      of ischemic heart disease is interpreted as compensatory reaction to elevation of
      myocardial glucose requirements.

PMID- 16091650
TI  - [The place of diuretics in the treatment of chronic heart failure. Part I].
AB  - In series of papers the authors analyze the literature data concerned with
      clinical pharmacology of four main classes of diuretics and their use in long
      term treatment of congestive chronic heart failure (CHF). Part I is devoted to
      basic clinical pharmacology of three main classes of diuretics -- loop, thiazide
      and potassium-sparing. The site of action in nephron, mechanisms and duration of
      action different loop and thiazide diuretics with emphasis to furosenide,
      torasemide, hydrochlorothiazide, metolazone and indapamide as well as
      contraindications and limitations for their use in the complex treatment of CHF
      are considered in detail. In long-term comparative studies showed long acting
      loop diuretic torasemide improved symptomatology and functional class of NYHA in
      patients with CHF in compared with furosenide. Thiazide-like diuretic indapamide
      does also act as vasodilator and decreases afterload of left ventricle of heart.
      But indapanide should be used with special caution because of their capacity to
      prolong the Q-T interval, which associates with polymorphic ventricular
      tachycardia, or torsades de poites.

PMID- 16091651
TI  - [Recommendations of the Working Group of European Society of Cardiology on
      diagnosis and treatment of pulmonary arterial hypertension].

PMID- 16091652
TI  - [The role of nitrates in the treatment of cardiological patients in accordance
      with principles of evidence based medicine and recommendations of their practical
      use].

PMID- 16091653
TI  - [Implantation of an extracardiac mesh in the treatment of dilated cardiomyopathy:
      the TOLK Study (Therapevticheskoe Operativnoe Lechenie Kardiomyopatye)].

PMID- 16091654
TI  - [Genetic factors of risk of ischemic heart disease development in patients with
      familial hypercholesterolemia].
AB  - Ischemic heart disease (IHD) develops in patients with familial
      hypercholesterolemia (FHC) 15-20 years earlier than in general population.
      However age of onset of the disease, its clinical manifestations are variable and
      not completely determined by cholesterol level and class of low density
      lipoprotein receptor mutations. AIM: To elucidate associations of some auxiliary
      genetic factors -- such as C151565T, C677T, R353Q polymorphisms of glycoprotein
      IIIa (GPIIIa), methylenetetrahydrofolate reductase (MTHFR) and coagulation factor
      VII genes, respectively, -- with the presence of IHD in patients with FHC.
      MATERIAL: Patients with clinical diagnosis of heterozygous FHC (n=198) with
      (n=106) and without (n=92) IHD. RESULTS: Patients with compared with those
      without IHD had similar frequency of T-allele of MTHFR gene (p=0.519), more often
      had T-allele of GPIIIa gene (23 and 12.5%, respectively, p=0.009), and less often
      -- Q-allele of factor VII gene (13 and 21%, respectively, p=0.048).
      Multifactorial analysis showed that risk of IHD was higher in patients with TT
      compared with CC genotype of the GPIIIa gene (OR 1.53, 95%CI 1.12-2.3), and lower
      in patients with RQ and QQ compared with RR genotype of factor VII gene (OR 0.41,
      95%CI 0.19-0.75). CONCLUSION: In patients with FHC polymorphisms in factor VII
      and GPIIIa genes but not C677T polymorphism of MTHFR gene were associated with
      the presence of IHD.

PMID- 16091655
TI  - [Long-term results of the use of TAIS coronary stent. Data of prospective follow
      up for 18 months].
AB  - The stent was placed in 528 coronary artery segments (39% complicated lesions) in
      448 patients with coronary artery disease and no previous invasive interventions.
      Immediate angiographic success was 99.8% with no case of acute thrombosis. Six
      months survival without restenosis, angina, and reintervention was 83%. Repeat
      angiography was carried out in 432 patients with 502 stented stenoses. Index of
      vessel diameter loss and level of restenosis were 0.32+/-0.26, and 15,6%,
      respectively. Fifty four patients with in-stent restenosis were subjected to
      successful repeat revascularization. Eighteen months survival without myocardial
      infarction and reintervention was 70%. The study demonstrated favorable effect of
      TAIS on 18 month rate of thrombosis and restenosis in patients with native
      atherosclerotic lesions.

PMID- 16091656
TI  - [Effect of mexicor on oxidative stress in acute myocardial infarction].
AB  - Mexicor (5% solution and capsules) was used in 40 of 80 conventionally treated
      patients with acute myocardial infarction. The drug was given intravenously for 5
      days, than intramuscularly (6-9 mg/kg) for 9 days and orally (0.1 mg t.i.d.)
      thereafter until discharge. Severity of oxidative stress was evaluated by K
      coefficient. Calculation of this coefficient required data on degree of oxidation
      of lipids in blood serum, serum levels of diene conjugates, malonic dialdehyde,
      alpha-tocopherol and ceruloplasmin. These parameters as well as activity of
      superoxide dismutase, glutathione peroxidase and catalase in erythrocytes were
      measured at admission, on days 2, 3, 7, 14 and at discharge. Mexicor treated
      compared with untreated (n=40) patients were characterized by diminished severity
      of oxidative stress at the account of lower levels of lipid peroxidation products
      and augmented compensatory potential of the endogenous antioxidant system.

PMID- 16091657
TI  - [Signs of metabolic syndrome in combinations of hypertension with coronary risk
      factors].
AB  - Anthropometric data, parameters of lipoprotein spectrum and carbohydrate
      metabolism were obtained from 115 men aged 34-67 years with hypertension.
      Hypertension combined with any other criterion of metabolic syndrome was
      associated with deviations of parameters of insulin resistance, blood pressure,
      body mass index, waist circumference, levels of cholesterol, low density
      lipoproteins and lipoprotein (a) similar to those observed in complete metabolic
      syndrome. Combinations of hypertension with hypercholesterolemia and/or excessive
      body mass were not associated with signs of insulin resistance in the presence of
      higher then in isolated hypertension values of body mass index, cholesterol, low
      density lipoprotein cholesterol.

PMID- 16091658
TI  - [The use of moexipril in postmenopausal women with hypertension and associated
      changes of bone mineral density].
AB  - Moexipril was given to 35 postmenopausal women with mild and moderate
      hypertension, menopausal syndrome and decreased bone mineral density. Blood
      pressure (BP) was measured before and in 1, 3, 6, and 12 months, while ultrasonic
      bone densitometry was carried out before and in 12 months of moexipril use.
      Significant lowering of systolic and diastolic BP, reduction of severity of
      climacteric syndrome occurred after 1, 3 and 6 months of moexipril use,
      respectively. After 12 months parameters of bone densitometry in moexipril
      treated women became better than in control group (p<0.01). Treatment was also
      associated with significant improvement of quality of life, diminished reactive
      anxiety and depression.

PMID- 16091659
TI  - [Improvement of restoration of heart function after ischemia by modified
      reperfusion solution].
AB  - AIM: To elucidate effect of saline reperfusion solution (RS) containing aspartic
      acid, glucose, mannit, and trisamine (pH 7.5+/-0.1 at 22 degrees C) on
      restoration of isolated perfused rat heart function. METHODS: After 20 minutes of
      initial perfusion hearts were sequentially subjected to 5 min of cardioplegia, 40
      min of normothermic total ischemia and 30-min reperfusion. Hearts of groups 1 and
      2 were stopped by hyper-potassium cardioplegic solution and after ischemia
      reperfused retrogradely for 5 min at 22 degrees C with Krebs solution and RS,
      respectively. This was followed by antegrade reperfusion with Krebs solution for
      25 min at 37 degrees C. In groups 3 and 4 cardioplegia was instituted by perfusol
      while reperfusion was carried out in the same way as in groups 1 and 2. RESULTS:
      RS significantly improved restoration of contractile and pump functions. Action
      of RS was more effective when it was used concomitantly with Perfusol. Thus by
      the end of reperfusion product of heart rate and left ventricular developed
      pressure was 76+/-7 and 56+/-2% of initial value in groups 4 and 3, respectively
      (p<0.05). External heart work calculated as product of cardiac output and mean
      aortic pressure was restored up to 72+/-4 and 35+/-3% of initial value in groups
      4 and 3, respectively (p<0.001). CONCLUSION: RS containing anaerobically
      utilizable substrates (aspartic acid, glucose), cellular membrane protectors, and
      antioxidants (mannit and trisamine), as well as optimal mixture of inorganic
      salts, significantly reduced damaging action of early reperfusion caused by
      activation of lipid peroxidation, Ca2+ overload and derangements of oxidative
      phosphorylation.

PMID- 16091660
TI  - [Cardioprotective effects of ischemic post-conditioning of the myocardium].
AB  - Phenomenon of ischemic post-conditioning of the myocardium (attenuation of
      myocardial damage during reperfusion resulting from interruption of early
      reperfusion period by repetitive short episodes of ischemia) was discovered in
      2003. This paper contains presentation of protective effects of ischemic post
      conditioning during ischemia-reperfusion of the myocardium, data on
      antiarrhythmic effects of post-conditioning in relation to persistent
      tachyarrhythmias during reperfusion, analysis of possible mechanisms of infarct
      limiting effect of post-conditioning, and perspectives of its clinical
      application.

PMID- 16091661
TI  - [Calcium induced calcium release from liver mitochondria of spontaneously
      hypertensive rats].
AB  - BACKGROUND: Disturbances of ionic homeostasis of cells and recently discovered
      cellular energy deficiency due to reduced ATP-synthesizing ability of
      mitochondria are the most important components of pathogenesis of primary
      hypertension. Therefore it is essential to elucidate relationship between
      functioning of ionic transport systems especially that of calcium transport and
      ATP-synthesizing ability of mitochondria. AIM: To study calcium induced calcium
      release from liver mitochondria of spontaneously hypertensive rats at various
      initial calcium concentrations in medium. RESULTS: We observed 30% lowering of
      maximal level of calcium uptake from the medium with unchanged rate of calcium
      uptake. Under conditions of calcium overload the rate of calcium release into the
      medium was 30% higher than in control. INTERPRETATION: These results evidenced
      for changes of functioning of mitochondrial permeability transition pores (MPT
      pores) during calcium overload appearing as acceleration of their switch to high
      conductance mode and equilibration of all ionic gradients on internal
      mitochondrial membrane. This can negatively affect ATP-synthesizing ability of
      mitochondria. Thus the presence of linkage between disturbance of ionic
      homeostasis and intracellular energy deficit was confirmed.

PMID- 16091662
TI  - [Incidence of main cardiovascular diseases among inhabitants of Kaunas in 1983
      2000].

PMID- 16091663
TI  - [Diagnostic value of serum concentrations of apolipoprotein B in male patients
      with suspected ischemic heart disease].

PMID- 16091664
TI  - [Individual sensitivity to antihypertensive drugs: genetic aspects].
AB  - Effective blood pressure lowering is essential for prevention of complications of
      arterial hypertension. Most current guidelines indicate diuretics, beta-blockers,
      angiotensin converting enzyme inhibitors, calcium channel blockers and
      angiotensin receptor blockers as main antihypertensive drugs. Genetic
      polymorphisms underlie pathophysiology of diseases and can affect efficacy of
      therapy. Method of investigation of pharmacogenetic interrelationships is based
      on analysis of genes encoding enzymes responsible for metabolism and transport of
      drugs as well as genes encoding main targets of drug action (receptors). Those
      polymorphic genes that encode elements of the system of metabolism, adsorption,
      transport, elimination of drugs, and main receptor systems are considered to be
      main gene-candidates for pharmacogenetic studies. Some drugs have well known
      genotypes determining efficacy of therapy as for instance alpha-adducin gene for
      diuretics. Data on other classes of drugs (e.g. calcium channel blockers) are
      scanty. Existing information on pharmacogenetic properties of antihypertensive
      drugs is presented in this review.

PMID- 16091665
TI  - [Obesity, remodeling of the heart and its morpho-functional changes.
      Controversial problems].

PMID- 16091666
TI  - [Nitrates. The place in contemporary therapy of ischemic heart disease].

PMID- 16091667
TI  - [Controlled randomized multicenter trial of a support device aimed at prevention
      of cardiac dilatation and remodeling].

PMID- 16091668
TI  - [Aspirin resistance: position paper of the working group on aspirin resistance of
      the international society on thrombosis and haemostasis].

PMID- 16091669
TI  - [Stroke and other thromboembolic complications of atrial fibrillation. Part VII.
      Prevention of cardioversion related thromboembolism].
AB  - In part VII of a series of papers on epidemiology and drug prevention of stroke
      and other thromboembolic complications of atrial fibrillation the authors analyze
      data on frequency and contemporary approaches to prevention of thromboembolic
      complications related to cardioversion. The stress is made on importance of
      prescription of indirect anticoagulants to all patients with duration of atrial
      fibrillation exceeding 48 hours. International normalized ratio should be
      controlled during anticoagulant therapy and be kept between 2.0 and 3.0 at least
      for 3-4 weeks before and after restoration of sinus rhythm. Absence of atrial
      thrombi at transesophageal echocardiography does not exclude possibility of
      thromboembolic complications of cardioversion conducted without anticoagulant
      therapy.

PMID- 16091670
TI  - [Physical exercise in secondary prevention of coronary heart disease].
AB  - Addition of life style intervention to pharmacological therapy has been shown to
      be essential for secondary prevention of cardiovascular diseases. The American
      Heart Association and American College of Sports Medicine propose physical
      activity of moderate intensity using dynamic exercise not causing myocardial
      ischemia and recommend four to five training sessions (30-40 min each) per week.
      Such activity has been shown to improve prognosis in coronary heart disease. This
      can be explained by exercise induced improvements of cardiovascular risk factors
      e.g. dyslipoproteinemia, insulin resistance and inflammation, normalization of
      endothelial function and retardation of atherosclerosis. Because of the strong
      evidence of the benefit of exercise in cardiovascular prevention and
      rehabilitation, this approach should be included in the complex therapy of
      cardiovascular patients.

PMID- 16091671
TI  - [Statins in prevention of attacks of atrial fibrillation].

PMID- 16091672
TI  - [Risk factors of cardiovascular diseases and chronic renal failure].
AB  - Analysis of results of recent studies shows that patients with renal failure have
      increased prevalence of risk factors of cardiovascular diseases including
      ischemic heart disease. This review contains discussion of effects of these risk
      factors on renal function, effectiveness of treatment and prevention.

PMID- 16091673
TI  - [Use of implanted intravascular catheters with subcutaneous "ports" in the
      treatment of surgical diseases].
AB  - Special implanted vascular catheters with subcutaneous "ports" were used in 120
      patients for infusions into arteries, veins and abdominal cavity. The results
      demonstrate high efficacy of this method in the treatment of surgical and cancer
      patients.

PMID- 16091674
TI  - [Reconstructive surgeries after extensive resections of anterior abdominal and
      chest walls for tumors].
AB  - Experience of reconstructive surgeries after extensive resections of anterior
      abdominal and chest walls performed on account of tumors is described. Recovery
      of integrity of anterior abdominal wall was performed by serial grafting with
      dura mater and polypropylene net implant. The thorax was repaired with special
      grafts of the ribs and sternum. The integrity of the skin was reestablished with
      either suturing of the separated flaps or transposition of myodermal flap on
      vascular pedicle.

PMID- 16091675
TI  - [Plastic surgery of postoperative abdominal hernias with polypropylene
      endoprosthesis].
AB  - One hundred and twenty-one patients with postoperative abdominal hernias of
      different size and location were treated, 103 of them underwent surgery with
      polypropylene endoprosthesis. Size of hernia was objectively assessed with an
      original method of X-ray-computed hernioabdominometry. The parameter presents as
      percentage of relative volume of hernia. Based on this index, hernias were
      classified by size in the following way: small -- relative volume 1.0 - 5.0%,
      middle-sized -- 5.1 -14,0%, large -- 14.1 - 18%, gigantic -- over 18.0%. Choice
      of a hernioplasty method depended on relative volume of postoperative hernia.
      Middle-sized hernias were indications for reconstructive surgery (complete
      adaptation of muscular and aponeurotic layers of abdominal wall), gigantic
      hernias - for correcting surgery (specified diastasis of muscular and aponeurotic
      layers was maintained). In large hernias the method of hernioplasty was
      individual depending on compensatory abilities of the patient. Postoperative
      complications (6.6%) were local and seen in 6.6% cases. There were no lethal
      outcomes and complications associated with endoprosthesis. Recurrences of hernia
      were not revealed in all 103 patients examined from 6 months to 2.5 years after
      surgery.

PMID- 16091676
TI  - [Nerve-preserving operations in surgery of rectal cancer].
AB  - Forty-eight patients underwent surgery for rectal cancer. In all the patients
      total mesorectumectomy was combined with one of the types of nerves-preserving
      surgeries. Three groups were divided depending on types of this surgery: 1--
      complete preservation of elements of autonomic nervous system (n=31), 2 --
      partial preservation (n=16), 3 -- complete ablation (n=1). In 30 patients of
      group 1 normal urination recovered on postoperative day 2 to 4. In 2 patients of
      group 2 stable atony of urinary bladder was seen, and in 2 patients -- reflex
      ischuria. In patient of group 3 normal urination recovered on day 14 after
      surgery without vesical tenesmus. Long-term results were assessed in 1 to 12
      months. No recurrences occurred. It is concluded that nerve-preserving surgeries
      improve functional results without loss of oncological radicalism.

PMID- 16091677
TI  - [Surgical treatment of chronic purulent diseases of extremities' bones and great
      joints].
AB  - Results of treatment of chronic purulent diseases of extremities' bones (n=414)
      and great joints (n=136) were analyzed. Combined treatment included surgical
      sanation of the inflammatory focus, autospongioplasty of residual cavities and
      defects after sequesterectomy (87 cases), extrafocal osteosynthesis, aspiration-
      flushing drainage. In 46 cases of severe suppuration in the zone of hip joint's
      endoprosthesis the resection arthroplasty was performed, in 43 cases of severe
      consequences of ankle-joint's fracture-dislocations -- compression talo-tibial
      and calcaneo-tibial arthrodesis. The follow-up was 15 years. Positive results
      were seen in 93.6% patients.

PMID- 16091678
TI  - [Grafting of carotid arteries].
AB  - Over 5-years, 167 reconstructive surgeries for stenosis of internal carotid
      arteries (ICA) were performed in 124 patients. Mean age of the patients was 63.5
      years. One hundred and twenty-nine carotid endarterectomies (CEAE) in 86 patients
      and 38 reconstructive operations of ICA in 38 patients were performed. There were
      no lethal outcomes in short- and long-term postoperative period. In short-term
      period after prosthesis of ICA restenosis was revealed in 3% patients, after
      eversion CEAE in 3% patients the embolism was seen, after standard CEAE
      restenosis were diagnosed in 8% patients and thrombosis -- in 3%. In long-term
      period after grafting of ICA the strokes were seen in 3%, stenosis -- in 6%
      patients, after eversion endarterectomy -- in 0 and 3% patients, and after
      standard CEAE -- in 3 and 24% patients, respectively. It is concluded that
      grafting of ICA is adequate surgical method of reconstruction and stroke
      prevention in specific variants of carotid atherosclerosis.

PMID- 16091679
TI  - [Clinical importance of early diagnosis of anaerobic non-clostridial infection].
AB  - Anaerobic infection is one of the most complicated problems of pyosurgery. The
      algorithm of examination of patients with anaerobic infection including
      intraoperative diagnosis is proposed. Surgical treatment playing also diagnostic
      role is the basis of combined treatment of soft tissues anaerobic infection.
      Early diagnosis and active surgical policy is one of the main ways of problem
      solving.

PMID- 16091680
TI  - [Differential treatment of acute pancreatitis].
AB  - Results of examination and treatment of 194 patients with acute pancreatitis were
      analyzed. It is revealed that the diagnosis of an etiopathogenetic form of acute
      pancreatitis is a key moment in the choice of the treatment. Patients with acute
      biliary pancreatitis and alimentary pancreonecrosis with pancreatogenic
      peritonitis require urgent surgical treatment at early stages of the disease.
      Laparoscopic cholecystectomy and Haulstad's drainage of the common bile duct are
      the procedures of choice in acute biliary pancreatitis. Alimentary
      pancreonecrosis with pancreatogenic peritonitis is the indication for
      videolaparoscopic drainage procedure and peritoneal dialysis as soon as possible
      after the disease beginning. This approach decreased lethality, number of
      complication and hospital stay.

PMID- 16091681
TI  - [Antisecretory therapy as a component of hemostasis in acute gastroduodenal ulcer
      bleedings].
AB  - Results of antisecretory therapy (pyrenzepin, H(2)-blockers, inhibitors of proton
      pump, octreotid) in 962 patients with acute gastroduodenal ulcer bleedings
      (AGDUB) were analyzed over 14-years period. Antisecretory treatment in AGDUB has
      principally different goals and potential depending on risk of bleeding's
      recurrence and morphological changes in tissue of gastroduodenal ulcer.
      Antisecretory therapy is the main treatment in high risk of AGDUB recurrence or
      before urgent surgery. Intravenous infusion of omeprazol has demonstrated the
      highest clinical efficacy due to maximal inhibition of gastric secretion and
      absence of negative influences on oxygen regimen in tissue of ulcer.

PMID- 16091682
TI  - [General anesthesia components during abdominal surgeries in patients with
      abdominal sepsis].
AB  - Results of optimization of general anesthesia during abdominal surgeries in
      patients with abdominal sepsis are analyzed. Inhibitors of proteases (transamin
      and antagozan) were used as non-opiate component in transduction stage. Central
      hemodynamics, gaseous metabolism and heart rate were analyzed in two groups of
      patients: group 1 -- anesthesia was carried out with inhibitors of proteases (32
      patients), group 2 -- without it (30 patients). High efficacy of the inhibitors
      was demonstrated. Inhibitors of proteases are indicated for anesthesia in
      patients with severe metabolic disorders associated with tissues hypoxia.
      Analgesic activity of transamin permits one to decrease doses of anesthetic
      medication with a cardiodepressive effect.

PMID- 16091683
TI  - [Causes, diagnosis and surgical treatment of strictures of lobar and segmental
      hepatic ducts].
AB  - Causes of strictures of lobar and segmental ducts after their injuries during
      open and laparoscopic cholecystectomy in 53 patients were analyzed. For
      correction of bile outflow precision non-wireframe (n=22) and wireframe (n=20)
      anastomoses were used. In 10 patients a combined anastomosis was established. In
      1 patient the external drainage of hepatic ducts was performed. After surgery 3
      patients died. 1-15 year long-term results were studied in 48 (96%) patients.
      Good results were achieved in 29 (60.5%), satisfactory -- in 13 (27%) patients.
      Recurrences of the strictures were diagnosed in 6 patients. It is concluded that
      dynamic control is necessary in patients operated on for bile ducts injuries.
      Underestimation of remittent cholangitis leading to biliary cirrhosis worsens
      prognosis of the disease.

PMID- 16091684
TI  - [Completion of esophagoplasty by means of transplant's remobilization].
AB  - Experience in completion of esophagoplasty by means of old transplant's
      remobilization in 54 patients is analyzed. Primary esophagoplasty in 52 patients
      was performed for burn stricture, 1 -- for traumatic stricture, 1 -- cancer of
      the esophagus. In 26 patients the cause of incomplete esophagoplasty was
      deficient length, in 11 -- necrosis, in 8 -- doubtful viability of transplant, in
      7 -- insufficiency of esophageal anastomosis, in 2 -- prolonged obliteration of
      it. Total remobilization was performed in 41 patients, partial -- in 13. Thirty
      six colic, 17 intestinal and 1 gastric transplants were used repeatedly.
      Esophagoplasty was completed in 50 patients, in 42 of them by one stage. In the
      rest 4 patients delayed pharyngoplasty was performed in the ENT clinic. One
      (1.8%) patient died in hospital due to insufficiency of proximal anastomosis and
      phlegmon of the thorax. Long-term result was studied in 40 patients: it was good
      in 25 patients, satisfactory -- in 12, bad -- in 3 patients.

PMID- 16091685
TI  - [Electrosurgical technologies in hemorrhoidectomy].
AB  - Based on experience in the treatment of 156 patients with chronic haemorrhoids, a
      comparative study of clinical efficiency of electrosurgical techniques in
      hemorrhoidectomy was carried out. Device-controlled bipolar electrocoagulation is
      characterized by less invasiveness compared with electrosurgical closed
      hemorrhoidectomy. Device-controlled bipolar electrocoagulation provides better
      repair and treatment of wound inflammation, shorter wound healing. Long-term
      results of device-controlled bipolar electrocoagulation were followed-up for 12
      months; a high level of life quality was achieved.

PMID- 16091686
TI  - [Relaparascopy in the treatment of postoperative complications].
AB  - Videoendoscopic technologies were used in the treatment of postoperative
      complications in 289 patients. All repeated laparoscopic procedures in early
      postoperative period after laparoscopic and laparotomic surgeries are integrated
      under the term "relaparoscopy". The algorithm of choice of a surgical method
      during laparoscopic examination is presented, technical principles of
      laparoscopic surgeries, indications and contraindications are formulated.
      Postoperative peritonitis was diagnosed in 66 (22.7%) patients, abdominal
      abscesses -- in 64 (22.1%), early intestinal obstruction -- in 58 (20.1%), bile
      outflow -- in 53 (18.2%), postoperative bleedings -- in 26 (9.1%), local liquid
      accumulations -- in 17 (5.8%), abdominal foreign bodies --- in 5 (1.9%) patients.
      Relaparoscopy was a final method of treatment of postoperative complications in
      74.5% patients. In 8.6% patients videoendoscopic procedures permitted performing
      some elements of surgery and to convert to minilaparotomy. In 16.9% patients
      indications for relaparotomy were revealed during relaparoscopy, after which
      dynamic relaparoscopy was used as programmed sanations.

PMID- 16091687
TI  - [Adenomas of the thyroid gland].
AB  - Different methods of diagnosis and treatment of thyroid gland's adenomas are
      analyzed. Current surgical treatment of euthyroid goiter is reviewed. Basing on
      long-term studies, the role and place of special diagnostic methods (ultrasonic
      scanning and fine needle biopsy) and indications for their use and surgical
      treatment were determined. The proposed treatment and diagnostic algorithm
      reduces the number of unjustified surgeries. When elective histological
      examination reveals thyroid cancer, reoperation is not necessary. The groups of
      patients with confirmed diagnosis "thyroid adenoma" and high cancer risk were
      distinguished. Optimization of differential diagnosis of thyroid adenoma and
      cancer based on cytological and immunogenotypic tests will help determine
      indications to surgical treatment in adequate scope.

PMID- 16091688
TI  - [Clinical, endoscopic and morphological criteria for assessing function of
      esophageal anastomosis].
AB  - Clinical and endoscopic data on 115 patients after surgery with creation of
      esophageal anastomosis was analyzed. Functional status of esophageal anastomosis
      was studied with x-ray, endoscopic, morphological, and US-assisted endoscopic
      METHODS: The findings provided information for development of functionally
      effective esophageal anastomosis criteria. Potential of US-assisted endoscopy was
      demonstrated. Objective and early diagnosis of the depth and intensity of
      inflammatory infiltration in early postoperative period allowed conduction of
      adequate treatment. The study of tissue structure in the zone of esophageal
      anastomosis in a late postoperative period discovers the cause of functional
      insufficiency of esophageal anastomosis.

PMID- 16091689
TI  - [Enterosorption and nutritious support with pectin-containing preparation in the
      treatment of stress immunodeficiency in peritonitis].
AB  - Fifty-eight patients aged from 18 to 65 years with peritonitis of different
      etiology in toxic and terminal phases were treated. Nasoenteral intubation,
      enterosorption and early nutritious support with pectin-containing preparation
      (PCP) were carried out in all the patients just after surgery with standard
      course of 5 days. Baseline data was compared with that after PCP-supported
      treatment. Powder products of red beet were used as PCP. Immunodeficiency in
      peritonitis is characterized by imbalance of stress-realizing and stress-limiting
      mechanisms of immunocompetent cells. Enterosorption and early nutritious support
      with PCP in peritonitis decrease the level of plasmic cortisol and enhance stress
      limiting reception that reduces a harmful effect of cortisol and reestablishes
      immunity.

PMID- 16091690
TI  - [Acute pancreatitis (protocols of diagnosis and treatment)].
AB  - Protocols of diagnosis and treatment of acute pancreatitis are presented.
      Definition based on pathogenesis of the disease is given. Phases of acute
      pancreatitis, features of diagnosis and treatment in each phase are analyzed.
      Terms of surgical treatment, main principles of postoperative treatment are
      discussed.

PMID- 16091691
TI  - [Sacral anesthesia in surgical treatment of soft tissues neoplasms of the lower
      extremities].
AB  - The experience with sacral anesthesia in surgical treatment of soft tissues'
      benign and malignant neoplasms of the lower extremities was analyzed. Benign
      tumors were the indications for surgical treatment in 19 patients, malignant
      tumors - in 11 patients. Various methods of sacral anesthesia are described,
      indications for this type of anesthesia and obtained results are discussed. It is
      concluded that sacral anesthesia in surgical treatment of soft tissues neoplasms
      of the lower extremities provides adequate anesthesia even without other types of
      anesthetic protection.

PMID- 16091692
TI  - [Method of suturing of median laparotomic wounds].
AB  - New method of suturing of median laparotomic wounds with interrupted twined (IT)
      suture is developed. Efficacy of IT-suture compared with other methods was
      evaluated in experiment (68 animals) and clinical study based on following data -
      time of elimination of local inflammation in wound area, number and nature of
      purulent complications, long-term results of treatment (postoperative ventral
      hernias). Use of IT-suture in clinical practice permitted to reduce number of
      purulent complications from 23.4 to 6.3% compared with noose sutures and from
      15.7 to 6.3% compared with uninterrupted ones. There were no eventrations,
      postoperative ventral hernias were seen in 2 (4%) patients.

PMID- 16091693
TI  - [Long-term results of excision of anal fissure in combination with lateral
      subcutaneous sphincterotomy].
AB  - One hundred and seventeen patients with anal fissure underwent fissure excision
      in combination with lateral subcutaneous sphincterotomy. The mean follow-up after
      treatment was 4.3 years. All the patients were questioned by the phone. Thirty
      six ones who had some symptoms were examined at outpatient department. The
      examination included physical examination, anorectal manometry, endorectal
      ultrasonography, irrigoscopy, defecography. Recurrences of anal fissure were
      revealed in 12 (10.2%) patients. The cause of recurrence was incomplete
      sphincterotomy. Different grade of anal incontinence was revealed in 23 patients:
      2 of them had soiling, 12 -- incontinence of the flatus, 8 -- incontinence of
      liquid faeces, 1 -- incontinence of solid faeces. In 4 patients the cause of anal
      incontinence was excessive sphincter section during sphincterotomy, in 16 --
      perineal descent syndrome, in 3 -- advanced age. It is concluded that it is
      necessary to modify surgical technique and to examine patients more carefully
      before surgery including anorectal manometry.

PMID- 16091694
TI  - [Pathogenetic mechanisms of peritonitis in acute small intestinal obstruction].
AB  - Microscopic changes in the walls of strangulated small intestine, morphology of
      their vascular and resorption elements, adaptive mechanisms were studied in
      experimental acute small intestinal obstruction. It is demonstrated that the main
      factor of pathogenesis of peritonitis in strangulate and obstructive small
      intestinal obstruction is morphofunctional changes of intraorganic
      microcirculation of the small intestine.

PMID- 16091695
TI  - [On omentum torsion].
AB  - Results of treatment of 10 patients aged from 16 to 62 years with omentum torsion
      were analyzed. The majority of them were hospitalized 1.5 -- 3 days after disease
      beginning. The main symptom was pains in the right half of the abdomen. Clinical
      picture was characterized by slow progress and late manifestation of peritoneal
      symptoms. All the patients underwent surgery under general anesthesia. Eight of
      them were suspected for acute appendicitis, 2 -- for acute cholecystitis. Five
      patients were operated during the first 2 hours, others -- from 6 hrs 40 min to
      20 hrs after hospitalization. In all the patients segmental torsion of the right
      side of the omentum on 360-720 degrees was revealed. Nine patients had abdominal
      hemorrhagic effusion. Resection of the affected part of the omentum with
      additional appendectomy in 5 cases was performed. Destruction in the appendix was
      revealed only in one patient. There were no complications and lethal outcomes.
      Problems of diagnostic and surgical policy are discussed.

PMID- 16091696
TI  - [Free-tension plastic surgery of inguinal canal in hernias].
AB  - Fifty-one patients with inguinal hernia underwent tension-free hernioplasty, 32
      of them were operated according to an original method which protects the
      spermatic cord against contact with net graft. This method permits to avoid
      recurrence, inguinodinia and dis-ejaculation.

PMID- 16091697
TI  - [Comparative study by pH-tests of the efficacy of antimicrobial agents in oral
      cavity].
AB  - The opportunity of use stimulated by sucrose solutions and urea test pH changes
      of the mixed saliva were investigated with the purpose of an estimation of
      efficiency of antiseptic and hygienic means action. Research is carried out on 37
      students who have been specially picked up in 3 groups: "A" -- with low activity
      of caries without periodontitis, "B" -- caries-susceptible and "C" -- with
      gingivitis and periodontitis. It appeared possible with the help of pH-measuring
      of saliva to compare antiseptic action in an oral cavity of 4 popular
      antiseptics: the combined gel with chlorhexidine and metronidazole, and also
      anticarious toothpaste in the form of application and in combination with
      cleaning teeth by a brush. The offered tests allow to reveal primary action of
      antiseptic means for the microflora causing either caries or inflammatory
      periodontal disease.

PMID- 16091698
TI  - [Structural properties of mixed saliva in persons with different levels of tooth
      resistance to caries].
AB  - Structural properties of mixed saliva were studied in 30 persons 16-18 years of
      age divided into 3 groups (10 persons in each) according to different levels of
      tooth resistance to caries -- 1st with high level of resistance (DMFT=0), 2nd
      with medium level of resistance (DMFT=4.3+/-0.82), 3rd with low level of
      resistance (DMFT=6.6+/-0.92). The difference between DMFT figures in groups 2 and
      3 was insignificant. In salivary filtrate (collected in the rest conditions and
      after 5 g sugar load) pH (by potentiometry) and optical density (by photoelectric
      colorimetry) were determined. 60 saliva samples were collected and 240
      determinations were made. In was found that 5 g sugar intake led to structural
      changes of oral fluid in all groups with different levels of tooth resistance to
      caries. But in persons with 0 caries incidence the oral fluid micelle resistance
      and saliva mineralizing capacity were higher than in persons with medium and low
      resistance to caries. The received data may be used for revelation of oral
      mineral homeostasis mechanisms and forecasting pathology arising in cases of its
      disturbance and for planning preventive and curative measures with consideration
      of their corrections depending upon the level of the individual resistance to
      caries.

PMID- 16091699
TI  - [Hemomicrocirculation in oral mucosa of alveolar dental crests in cases of their
      considerable atrophy as determined by Doppler flowmetry].
AB  - Doppler ultrasonography was used to study hemodynamic indices of blood
      circulation in gingival tissues in normal conditions and in cases of parodontal
      diseases. Such hemodynamic parameters as linear and volumetric blood speed were
      determined. It was shown that hemodynamic changes in tissue blood circulation in
      cases of initial inflammatory diseases had moderate intensity (decrease of linear
      and volumetric blood speed by 22-40%). As the severity of inflammation process in
      parodontal tissues increased (parodontitis of medium and severe degree) and in
      cases of parodontosis hemodynamic changes in tissue blood circulation acquired
      more pronounced nature (decrease of blood speed by 56-80%).

PMID- 16091700
TI  - [Mistakes and complications in stomatologic practice leading to neuro
      stomatological diseases].
AB  - There was described the results of mistakes and complications analysis in
      stomatological practice leading to neuro-stomatological diseases; their
      classification is proposed.

PMID- 16091701
TI  - [Possibility of development of oral and tissues diseases in young men with
      constitutional nutrition insufficiency].
AB  - Thorough examination of 114 young men of pre-constriction military training age
      disclosed that possibility of oral cavity pathology development is mainly
      determined by the indices DMFT, PMA, OHI-S and the following parameters of mixed
      saliva -- basic salivary flow, pH and Lactobacillus and Streptococcus mutans
      amounts. The degree of these factors changes expressed in scores identifies
      groups of low, medium and high probability of stomatologic pathology development
      and basing on this to individualize curative and preventive measures.

PMID- 16091702
TI  - [Efficacy of laryngeal mask use during anesthesia in cases of short-term
      operations in maxillofacial area].
AB  - 40 patients, with the pathology of maxillofacial area were investigated during
      the operation. The operation lasted 60.5+/-6.8 min. Combined intravenous
      anesthesia with propophol, phentanil, atracrium besylate was used for all
      patients. The utilization of a laryngeal mask (LM) for respiratory support was
      used in the first group (20 patients). An tracheal intubation (TI) was made in
      the second group (20 patients). In total myoplegia, the installation of LM was
      simple. Undesirable laryngo-pharyngeal reflexes were not noticed. The reaction of
      cardiovascular system while installing. LM was absent unlike TI. As for the gas
      exchange no difference was noticed in both groups (p>0.05). After the operation
      the patients of the first group recovered quicker than the patients of the second
      group (p<0.05). It is the result of reducing the amount of relaxants in the first
      group (p<0.05). Hence, anesthesia with LM may be regarded as alternative method
      of anesthesiological provision for a maxillofacial operations of short duration.

PMID- 16091703
TI  - [Comprehensive treatment of patients with chronic odontogenic perforative
      maxillary sinusitis].
AB  - The results of treatment of 244 patients with chronic odontogenic perforative
      maxillary sinusitis, using sparing sinusotomy show high effectiveness of the
      method. Number of complications, as well as period of disability decreased,
      economic effect were significant.

PMID- 16091704
TI  - [Philtrum formation in congenital cleft of upper lip].
AB  - Philtrum (labial groove) has aesthetic importance and governs individual features
      of human face. There are discussed the ways of philtrum reconstruction described
      in domestic and foreign literature. The main principles of the upper lip central
      part formation in one-sided congenital clefts are set out. Method of orbicularis
      oris muscle myoplasty by putting in the asymmetric stitches on deep and surface
      layers lets to reconstruct the philtrum and its column on the cleft side. Such
      philtrum reconstruction was performed in 90 cases of primary and secondary
      cheiloplasty in female patients with congenital one-sided clefts of the upper
      lips. Long-term results of 58 primary and 14 correcting operations on the upper
      lips were followed in the time period from 1 to 5 years. Good aesthetic results
      were achieved in 86.21 and 92.86% of the cases, respectively.

PMID- 16091705
TI  - [Correction of the short skin part of the septum nasi].
AB  - The method proposed by the authors has favourable features due to taking into
      account all deformities -- flattened nasal end, increased height of the upper lip
      skin part, in drawn position of ala nasi helix. Besides the incisions are made
      with taking into account the natural plicas, that allows to distribute tissues
      properly and make scarring practically un-noticeable.

PMID- 16091707
TI  - [Use of compomers in treatment of early childhood dental caries].
AB  - The purpose of this survey is to establish the effectiveness of the treatment of
      early childhood caries using compomers. The target group consists of 28 children
      aged from 20 to 47 months and presenting "early childhood caries". The team has
      done 126 fillings of vital frontal and distal teeth (61 of frontal and 65 of
      distal teeth) using the Glasiosite compomer by Voco. Fillings are evaluated
      immediately after polishing and after six after twelve months. Evaluation is
      achieved according to the Ryge classification scale, which reflects the type, the
      clinical status and the development of the filling. The information is processed
      through alternative analysis at importance level p<0.05. Our survey shows that
      most of the fillings can be classified as perfect. The remaining fillings made
      within the period of the survey are classified as satisfactory and do not need to
      be replaced. No unsatisfactory filling was found. Based on the features of the
      above compomers and the results of our survey we recommend them for filling of
      vital teeth of up to three-year old children.

PMID- 16091706
TI  - [Milk fluoridization efficacy in a controlled study and dental caries experience
      dynamics in conditions of wide availability of local F-containing means].
AB  - Cross-over, controlled, randomized and triple-blind study of F-milk efficacy and
      monitoring of F excretion with urine under conditions of wide availability of
      fluoride containing toothpastes was performed in Voronezh during last 10 years. F
      milk project increasingly covered annually from 10 to 15 thousand of pre-school
      children. From them 335 children (11 kindergarteners -- age 6 years) regularly
      consuming F-milk during 3 years and 175 children (6 kindergarteners -- age 6
      years) of the control group were examined. Statistics of the received data with 2
      tail t-test has shown that between dmf (1.59+/-1.82) in children consuming F-milk
      and dmf (2.58+/-2.67) in children of the control group there is significant
      difference (p<0.001) with 96% of the statistical power. When implementing F-milk
      for 10 years running there were collected and analyzed data on caries experience
      in children 3, 6, 9 and 12 years (2004 vs. 1994). There is considerable reduction
      of caries incidence in all age groups in 2004, probably due to F containing
      toothpastes wide use and very active hygienic education of the population in
      Voronezh. At the same time dmf index in 6 year old children receiving F-milk was
      by 39% lower than in their contemporaries from the control group. F-intake
      monitoring in children 3, 4, 5 and 6 years of age has shown that F-milk (daily
      appr. 0.2 l with the level 2.5 ppm) use is a very effective method of F
      deficiency elimination, leaving out any possibility of F-overdosage exceeding its
      physiologic needs.

PMID- 16091708
TI  - [Methods of primary dentofacial anomalies prevention used in therapeutic and
      preventive institutions of RF].
AB  - The study of the whole range of measures of primary dentofacial anomalies
      prevention has determined the most often used methods of their prophylaxis. It is
      also shown that consultations with specialists in the allied medical areas and
      use of technical preventive devices are underestimated. Information modalities
      for patients, hygiene (sanitary) education are not at due level. Small attention
      was paid to preventive examinations of children in the so-called organized
      collectives and to regular medical check-up of children population.

PMID- 16091709
TI  - [Choice of treatment strategy in patients with distal occlusion of Division I,
      Class II].
AB  - Comparison of 6 groups of patients with an Angle Class II, Division I
      malocclusions different by age and method of treatment has determined special
      features, which are typical for Class II malocclusion. It has revealed the
      complex of parameters, which determined strategy of treatment. Treatment with non
      extraction of a teeth can be realized in a case of more harmonious relation
      between mandible and maxilla with the teeth of a small size. 2 teeth can be
      extracted in case of the expressed disharmony between mandible and maxilla and a
      disproportion in the size of their teeth. 4 teeth can be extracted in case of the
      small size of mandible and maxilla and big size of a teeth.

PMID- 16091710
TI  - [Influence of the type of impression material, impression tray and making
      impression technology on the dimensional accuracy and depth of impression
      material penetration into "gingival sulcus". In vitro study].
AB  - Results of the profound study of influence of the type of impression material,
      impression tray and making impression technology upon main quality
      characteristics of the precise impression (dimensional accuracy and depth of
      impression material penetration into gingival sulcus) are reviewed. Original
      method to investigate depth of impression material penetration into gingival
      sulcus on experimental model is described. The impression technology exercises
      more influence on quality characteristics of the precise impression than type of
      the used material and impression tray. Optimal combination of different viscosity
      impression materials with technology of making impression has been defined.

PMID- 16091711
TI  - [Chronic ronchopathy -- a nosological entity of pathological realization of upper
      airways obstruction].
AB  - A comprehensive examination and therapy of 90 snoring and apnea patients treated
      in an ENT clinic of the Russian State Medical University have established similar
      features of the diseases: pathological mechanisms, clinical manifestations,
      stages, outcome. This enables differential diagnosis and change of the syndromal
      diagnosis "pathological snoring" for a nosological one -- chronic ronchopathy.
      The term "ronchopathy" originates from a Greek word "ronhus"-- snoring; the term
      "chronic" means development of the disease due to chronic pathology of the upper
      airways and progression of a clinical symptom -- snoring.

PMID- 16091712
TI  - [Prognostic value of hearing function in ischemic stroke].
AB  - The study of 70 patients with acute ischemic stroke has demonstrated that
      ischemic stroke is associated with central hypoacusis the symptoms of which are
      subjectively weak. It is suggested that development of neurosensory hypoacusis of
      the III-IV degree may serve a prognostic sign of a poor outcome of acute ischemic
      attack.

PMID- 16091713
TI  - [Audiometric and dynamometric parameters of functional brain asymmetry].
AB  - We examined influence of intensive noise on auditory and musculoskeletal system
      in series of audiometric and dynamometric tests. We considered Karhart's tooth
      asymmetry and asymmetry of muscular strength of the upper extremities. We
      demonstrate the significance of these parameters in diagnosis of functional
      cortical asymmetry and central hearing pathology; provide audiometric and
      dynamometric evidence of the structure of cortical auditory pathways, the
      integral function of the auditory cortex, pathophysiological nature of functional
      asymmetry and their correlation.

PMID- 16091714
TI  - [The effect of phonational load on parameters of cardiorespiratory system in
      hypotonic dysphonia].
AB  - Cardiointervalometry was used to investigate functional parameters of the
      cardiorespiratory system during text reading. A total of healthy women aged from
      17 to 28 years and 11 women with hypotonic dysphonia 17 to 31 years of age
      entered the study. Both groups exhibited a low index of parasympathetic component
      of cardiorhythm regulation in shortening of the RR-interval. Correlation
      inhalation/expiration has changed with prolongation of inhalation and shortening
      of expiration in reading in women suffering from hypotonic dysphonia. Parameters
      of the respiratory cycle at rest did not correlate with relevant parameters in
      reading text in both groups.

PMID- 16091715
TI  - [The use of real time visual feedback in the treatment of patients with increased
      fundamental frequency of voice].
AB  - To correct fundamental frequency (FF) in five juveniles with puberphonia and in
      five women with functional dysphonia, we used visual computer feedback (musical
      soft Circ FFT, Svante Granqvist). Visual computer control over FF alterations
      facilitated the above correction. This method is an additional tool to the armory
      of therapeutic measures to correct FF. It is especially useful for persons with
      tin ear.

PMID- 16091716
TI  - [Anatomic item of the human ethmoid bone -- bulla ethmoidalis uncinata].
AB  - A discovery was made in the N.N. Burdenko Voronezh State Medical Academy patented
      in 2002 -- earlier unknown anatomic item of human ethmoid bone -- bulla
      ethmoidalis uncinata. It is a pneumatized conjunction of the large ethmoid
      vesicle and the uncinate process located on the medial plate of ethmoid labyrinth
      constituting the upper part of the lateral nasal wall in the region of the middle
      nasal passage. The discovery concerns the field of medicine, i.e. human
      topographic anatomy, surgery, otorhinolaryngology.

PMID- 16091717
TI  - [Immune alterations in patients with laryngeal cancer at different stages].
AB  - The immune status was studied in 162 patients with laryngeal cancer (T2N0M0,
      T3N0M0, T4N1MX). Progression in these patients was associated with suppression of
      specific mechanisms of immune defense -- cytolysis of target cells and activation
      of CD4(+) lymphocytes. Cytolytic mechanisms were not compensated by involvement
      of other defense mechanisms, i.e. nonspecific, natural killers mediated.
      Dysgammaglobulinemia detected in laryngeal cancer patients can be considered as
      alteration associated with tumor damage to mucosa.

PMID- 16091718
TI  - [The role of nitric oxide in antimicrobial defense in chronic tonsillitis].
AB  - Nitric oxide (NO) degradation products were assayed in lacunar discharge in
      chronic compensated and decompensated tonsillitis before and after treatment on
      the ultrasound device Tonsillor. It was found that pretreatment concentration of
      NO degradation products (nitrites and nitrates) differed in decompensated and
      compensated chronic tonsillitis. The treatment reduced content of NO degradation
      products in both forms of tonsillitis. Use of indirect values of NO concentration
      are proposed for differential diagnosis between chronic compensated and
      decompensated tonsillitis as well as for monitoring of treatment efficacy.

PMID- 16091719
TI  - [The features of disorders lipidic change in patients with acute neurosensory
      hipoacusis of various genesis].

PMID- 16091720
TI  - [Efficacy of cytological diagnosis of nodular lesions of the neck].

PMID- 16091721
TI  - [Physician's approach in parapharyngeal tumors].

PMID- 16091722
TI  - [Treatment of patients with hearing functional system impaired as a result of
      explosion barotraumas].

PMID- 16091723
TI  - [A method of frontal sinus puncture].

PMID- 16091724
TI  - [Efficacy of Panclav 625 g in treatment of acute bacterial maxillary sinusitis].

PMID- 16091725
TI  - [Obligatory ENT care which must be provided by outpatient clinics of a large
      industrial city].

PMID- 16091726
TI  - [Rare cases of iatrogenic foreign bodies in the postoperative space].

PMID- 16091727
TI  - [The operation for juvenile angiofibroma of the nasopharynx as in terms of
      anesthesiology and critical care].

PMID- 16091728
TI  - [A rare case of osteoma in the maxillary sinus].

PMID- 16091729
TI  - [Vestibular function and equilibrium system function in patients with
      endolymphatic hydropse].

PMID- 16091730
TI  - [Etiology and pathogenesis of postintubation scarred stenosis of the larynx and
      trachea].

PMID- 16091732
TI  - Dual effect of Kras(D12) knockdown on tumorigenesis: increased immune-mediated
      tumor clearance and abrogation of tumor malignancy.
AB  - Activating mutations in the human KRAS proto-oncogene are acquired during the
      earliest stages of colorectal cancer development. If mutant KRAS is to be used as
      a target for therapy in colorectal cancer, tumor growth should depend on its
      continued presence. Here, we report that stable knockdown of Kras(D12) in murine
      C26 colorectal cancer cells by RNA interference resulted in loss of transformed
      properties in vitro. The incidence of subcutaneous tumor formation was reduced by
      60% and the lag time was increased sevenfold. Kras(D12)-knockdown tumors grew
      noninvasively and did not cause morbidity. Remarkably, some of the Kras(D12)
      knockdown tumors regressed spontaneously, which rendered these mice resistant to
      parental C26 tumor growth. In immune-deficient hosts, the incidence of tumor
      formation by Kras(D12)-knockdown cells was 100%. None of these tumors regressed
      spontaneously. We conclude that the reduced incidence of tumor formation by
      Kras(D12)-knockdown cells is due to tumor cell clearance by the host immune
      system, but not to an intrinsic inability of these cells to grow out as tumors.
      Interestingly, Kras(D12) knockdown resulted in increased production of
      interleukin 18 (Il-18), an immune-stimulatory cytokine that has been implicated
      in limiting colorectal tumor formation. Thus, mutant Kras(D12) suppresses Il-18
      production in colorectal tumor cells, which may contribute to evasion of the
      local immune system during tumor development.

PMID- 16091733
TI  - Commutators of PAR-1 signaling in cancer cell invasion reveal an essential role
      of the Rho-Rho kinase axis and tumor microenvironment.
AB  - We recently reported that proteinase-activated receptors type I (PAR-1) are
      coupled to both negative and positive invasion pathways in colonic and kidney
      cancer cells cultured on collagen type I gels. Here, we found that treatments
      with the cell-permeant analog 8-Br-cGMP and the soluble guanylate cyclase
      activator BAY41-2272, and Rho kinase (ROK) inhibition by Y27632 or a dominant
      negative form of ROK lead to PAR-1-mediated invasion through differential Rac1
      and Cdc42 signaling. Hypoxia or the counteradhesive matricellular protein
      SPARC/BM-40 (SPARC: secreted protein acidic rich in cysteine) overexpressed
      during cancer progression also commutated PAR-1 to cellular invasion through the
      cGMP/protein kinase G (PKG) cascade, RhoA inactivation, and Rac1-dependent or 
      independent signaling. Cultured primary cancer cells isolated from peritoneal and
      pleural effusions from patients with colon cancer or other malignant tumors
      harbored PAR-1, as shown by RT-PCR and FACS analyses. These malignant effusions
      also contained high levels of activated thrombin and fibrin, and induced a
      proinvasive response in HCT8/S11 human colorectal cancer cells. Our data
      underline the essential role of the tumor microenvironment and of several
      commutators targeting cGMP/PKG signaling and the RhoA-ROK axis in the control of
      PAR-1 proinvasive activity and metastatic potential of cancer cells in distant
      organs and peritoneal or pleural cavities. We also add new insights into the
      mechanisms linking the coagulation mediators thrombin and PAR-1 in the context of
      blood coagulation disorders and venous thrombosis often observed in cancer
      patients, as described in 1865 by Armand Trousseau.

PMID- 16091734
TI  - FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in
      hematopoietic malignancies.
AB  - Reccurent chromosomal translocation t(4;14) (p16.3;q32.3) occurs in patients with
      multiple myeloma (MM) and is associated with ectopic overexpression of fibroblast
      growth factor receptor 3 (FGFR3) that sometimes may contain the activation
      mutations such as K650E thanatophoric dysplasia type II (TDII). Although there
      have been significant advances in therapy for MM including the use of proteasome
      inhibitors, t(4;14) MM has a particularly poor prognosis and most patients still
      die from complications related to their disease or therapy. One potential
      therapeutic strategy is to inhibit FGFR3 in those myeloma patients that
      overexpress the receptor tyrosine kinase due to chromosomal translocation. Here
      we evaluated PKC412, a small molecule tyrosine kinase inhibitor, for treatment of
      FGFR3-induced hematopoietic malignancies. PKC412 inhibited kinase activation and
      proliferation of hematopoietic Ba/F3 cells transformed by FGFR3 TDII or a TEL
      FGFR3 fusion. Similar results were obtained in PKC412 inhibition of several
      different t(4;14)-positive human MM cell lines. Furthermore, treatment with
      PKC412 resulted in a statistically significant prolongation of survival in murine
      bone marrow transplant models of FGFR3 TDII-induced pre-B cell lymphoma, or a
      peripheral T-cell lymphoma associated TEL-FGFR3 fusion-induced myeloproliferative
      disease. These data indicate that PKC412 may be a useful molecularly targeted
      therapy for MM associated with overexpression of FGFR3, and perhaps other
      diseases associated with dysregulation of FGFR3 or related mutants.

PMID- 16091735
TI  - Colon cancer prognosis prediction by gene expression profiling.
AB  - This study assessed the possibility to build a prognosis predictor, based on
      microarray gene expression measures, in stage II and III colon cancer patients.
      Tumour (T) and non-neoplastic mucosa (NM) mRNA samples from 18 patients (nine
      with a recurrence, nine with no recurrence) were profiled using the Affymetrix
      HGU133A GeneChip. The k-nearest neighbour method was used for prognosis
      prediction using T and NM gene expression measures. Six-fold cross-validation was
      applied to select the number of neighbours and the number of informative genes to
      include in the predictors. Based on this information, one T-based and one NM
      based predictor were proposed and their accuracies were estimated by double cross
      validation. In six-fold cross-validation, the lowest numbers of informative genes
      giving the lowest numbers of false predictions (two out of 18) were 30 and 70
      with the T and NM gene expression measures, respectively. A 30-gene T-based
      predictor and a 70-gene NM-based predictor were then built, with estimated
      accuracies of 78 and 83%, respectively. This study suggests that one can build an
      accurate prognosis predictor for stage II and III colon cancer patients, based on
      gene expression measures, and one can use either tumour or non-neoplastic mucosa
      for this purpose.

PMID- 16091736
TI  - Both PPARgamma and PPARdelta influence sulindac sulfide-mediated p21WAF1/CIP1
      upregulation in a human prostate epithelial cell line.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) including sulindac sulfide are
      known to exert cancer chemopreventative activity in a range of cell lines. This
      activity has been shown to involve the upregulation of the cyclin-dependent
      kinase inhibitor p21WAF1/CIP1. It is also known that NSAIDs can act as peroxisome
      proliferator-activated receptor (PPAR) agonists and antagonists. In this study,
      we show that sulindac sulfide acts both as a PPARgamma agonist and a PPARdelta
      antagonist in an immortalized prostatic epithelial cell line (PNT1A). We utilized
      siRNA technology to show that PPARgamma is required for both growth inhibition
      and p21WAF1/CIP1 upregulation in response to sulindac sulfide treatment in PNT1A
      cells. In addition, the overexpression of PPARdelta partially rescued these cells
      from growth inhibition and also dramatically inhibited sulindac sulfide-mediated
      p21WAF1/CIP1 upregulation. Together these data identify a novel link between
      PPARgamma/PPARdelta/p21WAF1/CIP1 and the cancer chemo-preventative properties of
      NSAIDs.

PMID- 16091737
TI  - Exclusion of RUNX3 as a tumour-suppressor gene in early-onset gastric carcinomas.
AB  - Recent studies claim a critical role for RUNX3 in gastric epithelial homeostasis.
      However, conflicting results exist regarding RUNX3 expression in the stomach and
      its potential role as a tumour-suppressor gene (TSG) in gastric carcinogenesis.
      Our aim was to evaluate the role of RUNX3 in early-onset gastric carcinomas
      (EOGCs). We analysed 41 EOGCs for RUNX3 aberrations using loss of heterozygosity
      (LOH), fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC)
      analyses. LOH of markers flanking RUNX3 was relatively common, indicating that
      loss of the gene may play a role in gastric carcinogenesis. However, FISH
      analysis of selected cases and a panel of 14 gastric carcinoma-derived cell lines
      showed widespread presence of multiple copies of centromere 1. While RUNX3 copy
      numbers were generally equal to or fewer than those of centromere 1, at least two
      copies were present in almost all cells analysed. Accordingly, a subpopulation of
      tumour cells in 12/37 cases showed RUNX3 protein expression. However, expression
      was not detected in the adjacent nontumorous mucosa of any case. Together, these
      observations indicate that chromosome 1 aberrations occur frequently in EOGCs and
      are reflected in the LOH and IHC patterns found. Our findings refute a role for
      RUNX3 as a TSG in EOGCs.

PMID- 16091738
TI  - beta-Catenin regulates the expression of tenascin-C in human colorectal tumors.
AB  - Tenascin-C (TN-C) is a component of the extracellular matrix (ECM). It is
      expressed during development and re-expressed in many types of cancers, where it
      is involved in the modulation of adhesion and proliferation. TN-C expression is
      especially high at sites of epithelial mesenchymal transition (EMT), which are
      found frequently at the invasion front of well-differentiated human colorectal
      adenocarcinomas. Tumor cells in this compartment are characterized by a strong
      nuclear expression of the oncogenic transcription factor beta-catenin. Here, we
      demonstrate that TN-C is a beta-catenin target gene in human colorectal tumors.
      Thus, by far the most common mutations in colorectal tumors, found in the Wnt
      signaling pathway and leading to the stabilizing of beta-catenin, might influence
      invasion by altering adhesive properties and EMT of tumor cells.

PMID- 16091739
TI  - The retinoblastoma tumor suppressor protein is required for efficient processing
      and repair of trapped topoisomerase II-DNA-cleavable complexes.
AB  - Type II topoisomerases (TOP2) introduce transient double-stranded DNA breaks
      through a covalent TOP2-DNA intermediate. Anticancer agents like etoposide kill
      cells by trapping covalent TOP2-DNA cleavable complexes. Pathways influencing the
      repair of cleavable complexes are expected to be major determinants of
      therapeutic response to etoposide. Rb1 is required to enforce cell cycle
      checkpoints in response to DNA damage, but evidence for a direct role in the
      processing and repair of DNA lesions is lacking. We observe that degradation of
      trapped TOP2-cleavable complexes, liberation of DNA strand breaks, and repair of
      those breaks occurs more efficiently in cells expressing Rb1 protein (pRb). Cells
      lacking pRb are more sensitive to etoposide-induced cytotoxicity. Rb1-mediated
      processing and repair of TOP2-cleavable complexes is genetically separable from
      its ability to bind E2F and enforce DNA damage-induced cell cycle checkpoints.
      Rb1 protein binds both TOP2 and BRCA1 in intact cells, and pRb is required for
      association between TOP2 and BRCA1. These results suggest that pRb facilitates
      processing and repair of TOP2-cleavable complexes by recruiting proteins like
      BRCA1 to the damaged site. The functional status of pRb, therefore, may influence
      sensitivity to etoposide by facilitating the repair of trapped TOP2-DNA complexes
      as well as by enforcing cell cycle checkpoints.

PMID- 16091740
TI  - Roles of tyrosine residues 845, 892 and 922 in constitutive activation of murine
      FLT3 kinase domain mutant.
AB  - FLT3 tyrosine kinase domain (TKD) mutations are detected in approximately 7% of
      acute myeloid leukemia patients, and suggested to correlate with poor prognosis
      and confer resistance to FLT3 inhibitors. To explore activation mechanism of FLT3
      TKD mutation, we analysed critical tyrosine residues for the constitutive
      activation and downstream signaling of the mutant by generating a series of
      single Tyr --> Phe substitution mutant of all 22 cytoplasmic tyrosine residues of
      murine FLT3 TKD-mutant (mFLT3Asp838Val). Tyr845Phe, Tyr892Phe and Tyr922Phe
      substitutions suppressed the phosphorylation of mFLT3Asp838Val itself, the
      activation of Erk1/2, STAT3 and STAT5, and the factor-independent cell
      proliferation and survival. In contrast, these three Tyr --> Phe mutations
      partially suppressed but maintained the ligand-dependent activation and anti
      apoptotic activity of wild-type FLT3, suggesting that these tyrosine residues
      were more critical for the constitutive activation and signaling of
      mFLT3Asp838Val. These three Tyr --> Phe mutations also inhibited the constitutive
      activation of other FLT3 mutants bearing internal tandem duplication, Asp838Tyr
      or Ile839del. The suppression of mFLT3Asp838Val activation and signaling by these
      substitutions was partially recovered by shifting the culture temperature from 37
      to 33 degrees C, or by the introduction of Cdc37 and Hsp90. Taken together,
      Tyr845, Tyr892 and Tyr922 are the critical residues in mFLT3Asp838Val activation,
      possibly through stabilizing the active conformation of mFLT3Asp838Val.

PMID- 16091741
TI  - Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs.
AB  - The mechanism of action of chemotherapeutic drugs and their ability to induce
      multidrug resistance (MDR) are of relevance to cancer treatment. Overexpression
      of P-glycoprotein (Pgp) encoded by the MDR1 gene following chemotherapy can
      severely limit the efficacy of anticancer agents; however, the manner by which
      cells acquire high levels of Pgp has not been defined. Herein, we demonstrate
      that chemotherapeutic drugs induce specific epigenetic modifications at the MDR1
      locus, concomitant with MDR1 upregulation mediated by transcriptional activation,
      and a potential post-transcriptional component. We have established that the
      mechanisms are not mutually exclusive and are dependent on the methylation state
      of the MDR1 promoter. MDR1 upregulation did not result in further changes to the
      CpG methylation profile. However, dramatic changes in the temporal and spatial
      patterning of histone modifications occurred within the 5' hypomethylated region
      of MDR1, directly correlating with MDR1 upregulation. Specifically, drug-induced
      upregulation of MDR1 was associated with increases in H3 acetylation and
      induction of methylated H3K4 within discrete regions of the MDR1 locus. Our
      results demonstrate that chemotherapeutic drugs can actively induce epigenetic
      changes within the MDR1 promoter, and enhance the MDR phenotype.

PMID- 16091742
TI  - c-Abl regulates early growth response protein (EGR1) in response to oxidative
      stress.
AB  - c-Abl is a tyrosine kinase that can act as a regulator of cell growth and
      apoptosis in response to stress. Using cell lines expressing c-Abl in an
      inducible manner, we identified genes whose expression was regulated by c-Abl
      kinase activity. Microarray analysis indicated that Early Growth Response-1
      (EGR1) gene expression is induced by c-Abl kinase activity, which was confirmed
      at the message and protein levels. Promoter mapping experiments revealed that c
      Abl utilizes three distal serum response elements (SREs) in the EGR1 promoter,
      which are transactivated by mitogen/extracellular receptor kinase (MEK/ERK)
      signaling. PD 95089, a specific inhibitor of MEK/ERK signaling, attenuated c-Abl
      mediated upregulation of EGR1 expression in a dose-dependent manner. Similar
      results were obtained by using a dominant-negative mutant of
      mitogen/extracellular kinase. Significantly, hydrogen peroxide-induced EGR1
      expression appears to be mediated by c-Abl, as cells expressing dominant negative
      c-Abl, and c-Abl-/- murine embryonic fibroblasts, are completely defective in
      hydrogen peroxide-induced EGR1 expression. In addition, c-Abl-induced apoptosis
      is partially mitigated by EGR1 activity, as cells devoid of EGR1 expression
      undergo reduced rates of c-Abl-induced apoptosis. Together, these results
      indicate that c-Abl promotes the induction of EGR1 through the MEK/ERK pathway in
      regulating apoptotic response to oxidative stress.

PMID- 16091743
TI  - The nuclear receptor liver receptor homolog-1 is an estrogen receptor target
      gene.
AB  - Liver receptor homolog-1 (LRH-1) is a nuclear receptor previously known to have
      distinct functions during mouse development and essential roles in cholesterol
      homeostasis. Recently, a new role for LRH-1 has been discovered in tumor
      progression, giving LRH-1 potential transforming functions. In order to identify
      critical factors stimulating LRH-1 expression leading to deregulated cellular
      proliferation, we studied its expression and its regulation in several breast
      cancer cell lines. We observed that LRH-1 expression was increased in estrogen
      receptor (ER) alpha expressing cell lines, whereas weak-to-no expression was
      found in nonexpressing ERalpha cell lines. In MCF7, LRH-1 expression was highly
      induced after treatment with 17beta-estradiol (E2). This transcriptional
      regulation was the result of a direct binding of the ER to the LRH-1 promoter, as
      demonstrated by gelshift and chromatin immunoprecipitation assays. Interestingly,
      siRNA-mediated inactivation of LRH-1 decreased the E2-dependent proliferation of
      MCF7 cells. Finally, LRH-1 protein expression was detected by
      immunohistochemistry in tumor cells of human mammary ductal carcinomas.
      Altogether, these data demonstrate that LRH-1 is transcriptionally regulated by
      the ER alpha and reinforce the hypothesis that LRH-1 could exert potential
      oncogenic effects during breast cancer formation.

PMID- 16091744
TI  - Melphalan-induced apoptosis in multiple myeloma cells is associated with a
      cleavage of Mcl-1 and Bim and a decrease in the Mcl-1/Bim complex.
AB  - Multiple myeloma (MM) is a rapidly fatal plasma-cell malignancy that evolves
      mainly in the bone marrow. Melphalan is widely used to treat patients with MM but
      as yet its mechanisms of action are poorly documented. In the current study, we
      demonstrate that melphalan induces a drastic downregulation of Mcl-1L, Bcl-x(L)
      and BimEL in human melphalan-sensitive myeloma cells while the most potent
      proapoptotic isoforms, BimL and S, are affected to a lesser extent. Moreover, Mcl
      1L and BimEL disappearance is associated with the generation of proapoptotic
      cleaved forms generated by a caspase cleavage. In myeloma cells, we have
      previously shown that Mcl-1 neutralizes the proapoptotic function of Bim and
      therefore, prevents the activation of death effectors. In this study, we
      demonstrate that melphalan disrupts the Mcl-1/Bim complex whereas the Bcl-2/Bim
      complex is not modified. The disappearance of full length Mcl-1 allows the
      release of Bim isoforms, particularly L and S, which can exert their proapoptotic
      function and leads to Bax activation and cytochrome c release. Thus, we can
      hypothesize that the cleaved 26 kDa proapoptotic Mcl-1 and the 19 and 12 kDa of
      Bim, generated during melphalan treatment could contribute to the amplification
      loop of apoptosis.

PMID- 16091745
TI  - BBC3 mediates fenretinide-induced cell death in neuroblastoma.
AB  - Fenretinide (4-HPR) is a synthetic retinoid whose apoptosis-inducing effects have
      been demonstrated in many tumor types. The precise mechanism of its apoptotic
      action is not fully understood. To further study the mechanism by which 4-HPR
      exerts its biological effects in neuroblastoma (NB) and to identify the genes
      that contribute to the induction of apoptosis, we determined the sensitivity of
      eight NB cell lines to 4-HPR. Additionally, cDNA microarray analysis was
      performed on a 4-HPR-sensitive cell line to investigate the temporal changes in
      gene expression, primarily focusing on the induction of proapoptotic genes. BBC3,
      a transcriptionally regulated proapoptotic member of the BCL2 family, was the
      most highly induced proapoptotic gene. Western analysis confirmed the induction
      of BBC3 protein by 4-HPR. Furthermore, the induction of BBC3 was associated with
      the sensitivity to this agent in the cell lines tested. Finally we demonstrated
      that BBC3 alone is sufficient to induce cell death in the 4-HPR-sensitive and
      resistant NB cell lines, and that siRNA against BBC3 significantly decreases
      apoptosis induced by 4-HPR. Our results indicate that BBC3 mediates cell death in
      NB cells in response to 4-HPR.

PMID- 16091746
TI  - The aryl hydrocarbon receptor constitutively represses c-myc transcription in
      human mammary tumor cells.
AB  - The aryl hydrocarbon receptor (AhR) is an environmental carcinogen-activated
      transcription factor associated with tumorigenesis. High levels of apparently
      active AhR characterize a variety of tumors, even in the absence of environmental
      ligands. Despite this association between transformation and AhR upregulation,
      little is known of the transcriptional consequences of constitutive AhR
      activation. Here, the effects of constitutively active and environmental ligand
      induced AhR on c-myc, an oncogene whose promoter contains six AhR-binding sites
      (AhREs (aryl hydrocarbon response elements)), were investigated. A reporter
      containing the human c-myc promoter, with its six AhREs and two NF-kappaB-binding
      sites, was constructed. This vector, and variants with deletions in the NF-kappaB
      and/or AhR-binding sites, was transfected into a human breast cancer cell line,
      Hs578T, which expresses high levels of apparently active, nuclear AhR. Results
      indicate that: (1) the AhR constitutively binds the c-myc promoter; (2) there is
      a low but significant baseline level of c-myc promoter activity, which is not
      regulated by NF-kappaB and is not affected by an environmental AhR ligand; (3)
      deletion of any one of the AhREs has no effect on constitutive reporter activity,
      while deletion of all six increases reporter activity approximately fivefold; (4)
      a similar increase in reporter activity occurs when constitutively active AhR is
      suppressed by transfection with an AhR repressor plasmid (AhRR); (5) AhRR
      transfection significantly increases background levels of endogenous c-myc mRNA
      and c-Myc protein. These results suggest that the AhR influences the expression
      of c-Myc, a protein critical to malignant transformation.

PMID- 16091747
TI  - FGF1 inhibits p53-dependent apoptosis and cell cycle arrest via an intracrine
      pathway.
AB  - We analysed the relationships between p53-induced apoptosis and the acidic
      fibroblast growth factor 1 (FGF1) survival pathway. We found that p53 activation
      in rat embryonic fibroblasts induced the downregulation of FGF1 expression. These
      data suggest that the fgf1 gene is a repressed target of p53. Unlike
      extracellular FGF1, which has no effect on p53-dependent pathways, intracellular
      FGF1 inhibits both p53-dependent apoptosis and cell growth arrest via an
      intracrine pathway. FGF1 increases MDM2 expression at both mRNA and protein
      levels. This increase is associated with an acceleration of p53 degradation,
      which may partly account for the ability of endogenous FGF1 to counteract p53
      pathways. In the presence of FGF1, p53 was unable to transactivate bax, but no
      modification of p21 gene transactivation was observed. As Bax is an essential
      component of the p53-dependent apoptosis pathway, this suggests that
      intracellular FGF1 inhibits p53 pathways not only by decreasing the stability of
      p53, but also by modifying some of its transactivation properties. In conclusion,
      we showed that p53 and FGF1 pathways may interact in the cell to determine cell
      fate. Deregulation of one of these pathways modifies the balance between cell
      proliferation and cell death and may lead to tumor progression.

PMID- 16091748
TI  - Constitutive activation of the CD40 pathway promotes cell transformation and
      neoplastic growth.
AB  - CD40, a tumour necrosis factor (TNF) receptor family member, is expressed in a
      variety of cell types, including B lymphocytes, macrophages, fibroblasts,
      endothelial and epithelial cells, and this widespread expression is likely to
      account for its central role in normal physiology and disease pathogenesis. In
      this study, we provide evidence to support a role for constitutive CD40
      signalling in cell transformation. We show that the ligand for CD40 (CD40L/CD154)
      is expressed in CD40-positive human breast tumour biopsies, suggesting that the
      constitutive activation of the CD40 receptor in vivo may contribute to the
      oncogenic process. Coexpression of CD40 and CD40L confers oncogenic effects on
      immortalized human epithelial cells in vitro, increasing their proliferation,
      motility and invasion. Expression of LMP:CD40, a hybrid molecule comprising the N
      terminus and transmembrane domains of the Epstein-Barr virus-encoded latent
      membrane protein-1 (LMP1) fused to the cytoplasmic tail of CD40, mimics a
      constitutively active CD40 receptor and promotes the transformation of
      immortalized rodent fibroblasts in vitro and their oncogenicity in vivo. The
      observed effects of aberrant CD40 activation on cell transformation are largely
      diminished upon suppression of the oncogenic NF-kappaB signalling pathway. Taken
      together, our results suggest a role for the constitutive engagement of the
      CD40L/CD40/NF-kappaB activation pathway in cell transformation and neoplastic
      growth. Strategies that neutralize this pathway may therefore be useful in cancer
      treatment and prevention.

PMID- 16091749
TI  - PK11195 potently sensitizes to apoptosis induction independently from the
      peripheral benzodiazepin receptor.
AB  - 1-(2-Chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195) is a
      prototypic ligand of the peripheral benzodiazepine receptor (PBR), a
      mitochondrial outer membrane protein. PK11195 can be used to chemosensitize tumor
      cells to a variety of chemotherapeutic agents, both in vitro and in vivo. PK11195
      has been suggested to exert this effect via inhibition of the multiple drug
      resistance (MDR) pump and by direct mitochondrial effects which could be mediated
      by the PBR. Here, we established a model system in which PK11195 and another PBR
      ligand, 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2
      one (Ro5-4864), sensitize to nutrient depletion-induced cell death. In this MDR
      independent model, PK11195 and Ro5-4864 are fully active even when the PBR is
      knocked down by small interfering RNA. Cells that lack PBR possess low-affinity
      binding sites for PK11195 and Ro5-4864. The starvation-sensitizing effects of
      PK11195 are not due to a modulation of the adaptive response of starved cells,
      namely autophagy and NF-kappaB activation. Rather, it appears that the
      combination of PK11195 with autophagy or NF-kappaB inhibitors has a potent
      synergistic death-inducing effect. Starved cells treated with PK11195 exhibit
      characteristics of apoptosis, including loss of the mitochondrial transmembrane
      potential, mitochondrial cytochrome c release, caspase activation and chromatin
      condensation. Accordingly, stabilization of mitochondria by overexpression of Bcl
      2 or expression of the viral mitochondrial inhibitor (vMIA) from cytomegalovirus
      inhibits cell death induced by PK11195 plus starvation. Thus, PK11195 potently
      sensitizes to apoptosis via a pathway that involves mitochondria, yet does not
      involve the PBR.

PMID- 16091750
TI  - BCL11B functionally associates with the NuRD complex in T lymphocytes to repress
      targeted promoter.
AB  - BCL11 genes play crucial roles in lymphopoiesis and have been associated with
      hematopoietic malignancies. Specifically, disruption of the BCL11B (B-cell
      chronic lymphocytic leukemia/lymphoma 11B) locus is linked to T-cell acute
      lymphoblastic leukemia, and the loss of heterozygosity in mice results in T-cell
      lymphoma. BCL11 proteins are related C2H2 zinc-finger transcription factors that
      act as transcriptional repressors. Here, we demonstrate the association of the
      endogenous BCL11B with the nucleosome remodeling and histone deacetylase (NuRD)
      complex, one of the major transcriptional corepressor complexes in mammalian
      cells. BCL11B complexes from T lymphocytes possess trichostatin A-sensitive
      histone deacetylase activity, confirming the functionality of the complexes.
      Analysis of the BCL11B-NuRD association demonstrated that BCL11B directly
      interacted with the metastasis-associated proteins MTA1 and MTA2 through the
      amino-terminal region. We provide evidence for the functional requirement of MTA1
      in transcriptional repression mediated by BCL11B through the following: (1)
      overexpression of MTA1 enhanced the transcriptional repression mediated by
      BCL11B, (2) knockdown of MTA1 expression by small interfering RNA inhibited
      BCL11B transcriptional repression activity and (3) MTA1 was specifically
      recruited to a BCL11B targeted promoter. Taken together, these data support the
      hypothesis that the NuRD complex mediates transcriptional repression function of
      BCL11B.

PMID- 16091751
TI  - Reduced cell turnover in lymphocytic monkeys infected by human T-lymphotropic
      virus type 1.
AB  - Understanding cell dynamics in animal models have implications for therapeutic
      strategies elaborated against leukemia in human. Quantification of the cell
      turnover in closely related primate systems is particularly important for rare
      and aggressive forms of human cancers, such as adult T-cell leukemia. For this
      purpose, we have measured the death and proliferation rates of the CD4+ T
      lymphocyte population in squirrel monkeys (Saimiri sciureus) infected by human T
      lymphotropic virus type 1 (HTLV-1). The kinetics of in vivo bromodeoxyuridine
      labeling revealed no modulation of the cell turnover in HTLV-1-infected monkeys
      with normal CD4 cell counts. In contrast, a substantial decrease in the
      proliferation rate of the CD4+ T population was observed in lymphocytic monkeys
      (e.g. characterized by excessive proportions of CD4+ T lymphocytes and by the
      presence of abnormal flower-like cells). Unexpectedly, onset of HTLV-associated
      leukemia thus occurs in the absence of increased CD4+ T-cell proliferation. This
      dynamics significantly differs from the generalized activation of the T-cell
      turnover induced by other primate lymphotropic viruses like HIV and SIV.

PMID- 16091752
TI  - Inhibition of clonogenic tumor growth: a novel function of Smac contributing to
      its antitumor activity.
AB  - While second mitochondria derived activator of caspase (Smac) has been described
      to sensitize for apoptosis, its effect on cell viability in the absence of
      apoptotic stimuli has remained unclear. Here, we report that Smac inhibits
      clonogenic tumor growth by blocking random migration and proliferation and by
      enhancing apoptosis in a cell density and cell type dependent manner in SH-EP
      neuroblastoma cells. Inhibition of clonogenic survival by overexpression of full
      length or processed Smac strictly depended on low cell density, and was
      reversible by replatement at high density. We discovered that Smac inhibits cell
      motility and random migration at low cell density. In addition, Smac enhanced
      apoptosis and inhibited protein, but not mRNA expression of XIAP, survivin and
      other short-lived proteins (FLIP, p21), indicating that Smac may globally inhibit
      protein expression. Also, Smac inhibited proliferation and increased
      polynucleation with no evidence for polyploidy, cell cycle arrest or senescence
      indicating that Smac impaired cell division. Interestingly, inhibition of
      clonogenic capacity by Smac occurred independent of its apoptosis promoting
      activity. By demonstrating that Smac restrains clonogenic tumor growth, our
      findings may have important implications for control of tumor growth and/or its
      metastatic spread. Thus, Smac agonists may be useful in cancer therapy, for
      example, for tumor control in minimal residual disease. Oncogene (2005) 24, 7190
      7202. doi:10.1038/sj.onc.1208876; published online 8 August 2005.

PMID- 16091753
TI  - The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a
      new PCM1-JAK2 fusion gene.
AB  - Several tyrosine kinase genes are involved in chromosomal translocations in
      chronic myeloproliferative disorders, but there are still uncharacterized
      translocations in some cases. We report two such cases corresponding to atypical
      chronic myeloid leukaemia with a t(8;9)(p22;p24) translocation. By fluorescence
      in situ hybridisation (FISH) on the corresponding metaphases with a bacterial
      artificial chromosome probe encompassing the janus kinase 2 (JAK2) gene at 9p24,
      we observed a split for both patients, suggesting that this gene was rearranged.
      The locus at 8p22 contains different candidate genes including the pericentriolar
      material 1 gene (PCM1), already implicated in reciprocal translocations. The
      rearrangement of the PCM1 gene was demonstrated by FISH, for both patients. By RT
      PCR, we confirmed the fusion of 3' part of JAK2 with the 5' part of PCM1.
      Sequence analysis of the chimeric PCM1-JAK2 mRNA suggests that the putative
      protein displays the coiled-coil domains of PCM1 and the tyrosine kinase domain
      of JAK2. This new translocation identifies JAK2 as a possible therapeutic target
      for compounds with anti-tyrosine kinase activity.

PMID- 16091754
TI  - Effect of Herceptin on the development and progression of skeletal metastases in
      a xenograft model of human breast cancer.
AB  - We examined the effects of Herceptin, a bioengineered monoclonal antibody
      directed against Her-2/neu oncogene on skeletal metastasis using a xenograft
      model of breast cancer. Treatment of Her-2 overexpressing human breast cancer
      cells BT-474 with Herceptin caused a dose-dependent decrease in cell
      proliferation. In in vivo studies, BT-474 cells (1 x 10(5)) were injected into
      the left ventricle of female BALB/c nu/nu mice. Intraperitoneal (i.p.) infusion
      of Herceptin (1 mg/kg twice a week for 5 weeks) from the day of tumor cell
      inoculation or at the time of radiologically detectable skeletal metastasis
      either slowed the development or prevented the progression of skeletal metastasis
      as compared to control groups of animals receiving nonspecific IgG. Bone
      histological analysis of long bones showed the ability of Herceptin to reduce the
      ratio of tumor volume to bone volume as well as mitotic index, effects that were
      more pronounced when Herceptin treatment was initiated from the day of tumor cell
      inoculation. While immunohistochemical analysis of long bones showed no
      difference in the production of Her-2, phosphorylated (P) Her-2 and MAPK, a
      significantly lower level of P-MAPK was seen in bones of Herceptin treated
      animals. These studies demonstrate the ability of Herceptin to inhibit the
      development and abrogate the progression of skeletal metastases associated with
      breast cancer by blocking the HER-2-mediated signaling pathways.

PMID- 16091755
TI  - Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2
      tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of
      ErbB2-overexpressing breast cancer cells.
AB  - Antibodies and small molecule tyrosine kinase inhibitors targeting ErbB2 exhibit
      distinct, noncross resistant mechanisms of action. Here, apoptosis of ErbB2
      overexpressing breast cancer cells was enhanced by combining lapatinib, an
      inhibitor of ErbB1 and ErbB2 tyrosine kinases, with anti-ErbB2 antibodies,
      including (i) trastuzumab, a humanized monoclonal antibody, and (ii) pAb, rabbit
      polyclonal antisera generated by vaccination with a human ErbB2 fusion protein.
      Treating ErbB2-overexpressing breast cancer cell lines with a relatively low
      concentration of lapatinib alone resulted in a minimal increase in tumor cell
      apoptosis with an associated decrease in steady-state protein levels of p-ErbB2,
      p-Akt, p-Erk1/2, and notably survivin, compared to baseline. Exposure to pAb
      alone reduced total ErbB2 protein, disrupting ErbB3 transactivation, leading to a
      marked inhibition of p-Akt; however, survivin protein levels remained unchanged
      and apoptosis only increased slightly. Treatment with trastuzumab alone had
      relatively little effect on survivin and apoptosis was unaffected. Combining
      lapatinib with either pAb or trastuzumab markedly downregulated survivin protein
      and enhanced tumor cell apoptosis. The association between the inhibition of
      survivin and enhanced apoptosis following the combination of ErbB2-targeted
      therapies provides a biological effect in order to identify therapeutic
      strategies that promote tumor cell apoptosis and might improve clinical response.

PMID- 16091756
TI  - Plasminogen activator inhibitor-1 as a potential marker for the malignancy of
      colorectal cancer.
AB  - To test the hypothesis that plasminogen activator inhibitor-1 (PAI-1) may serve
      as a candidate marker for the malignancy of colorectal cancer (CRC), we performed
      a quantitative RT-PCR for PAI-1 gene and evaluated the possible relationship
      between PAI-1 gene expression levels and clinicopathological findings in CRC. A
      significant increase in PAI-1 expression scores was observed in lymph node
      metastasis-positive CRCs (2.19 +/- 0.43) compared to negative ones (0.35 +/-
      0.42) (P = 0.0037) as well as in distant metastasis-positive CRCs (3.50 +/- 1.18)
      compared to negative ones (0.99 +/- 0.30). The PAI-1 expression score markedly
      increased with the tumour stage (P = 0.0063; ANOVA test). Moreover, multivariate
      analysis revealed the PAI-1 expression score to be a strong and independent
      prognostic factor for CRC (P = 0.0432). These results suggested that PAI-1 might
      serve as a new parameter for the prediction of prognoses in CRC.

PMID- 16091757
TI  - Oncofoetal fibronectin--a tumour-specific marker in detecting minimal residual
      disease in differentiated thyroid carcinoma.
AB  - Supposedly, thyrocyte-specific transcripts such as thyroglobulin (Tg) and thyroid
      stimulating hormone receptor (TSH-R) were proposed to be useful for the diagnosis
      of circulating tumour cells in patients suffering from differentiated thyroid
      carcinoma (DTC). However, several research groups reported blood-borne Tg
      transcripts in healthy individuals. This study determines in particular the
      origin of Tg mRNA in nucleated blood cells and analyses whether other tumour
      associated sequences are absent in leukocytes, but widely expressed in DTC.
      Therefore, expression analyses for Tg, TSH-R, cytokeratin 19 (CK 19), human
      telomerase reverse transcriptase (hTERT) and oncofoetal fibronectin (onfFN) were
      carried out using cDNAs derived from (1) leukocyte fractions, (2) 18 follicular
      thyroid carcinomas (FTCs) and 48 papillary thyroid carcinomas (PTCs), and (3)
      leukocytes of two thyrocyte-depleted individuals treated for C-cell carcinoma of
      the thyroid. Expression of onfFN was additionally analysed by semiquantitative RT
      PCR and by quantitative fluorescence-based real-time PCR. Tg and TSH-R expression
      was demonstrated not only in both athyroid individuals, but in all leukocyte
      subgroups tested, while hTERT was absent in resting CD4+ cells and only weakly
      expressed in the CD8+ group. CK 19 was notable in each leukocyte population
      except for resting CD14(+), as well as for activated and resting CD19+ cells. All
      blood cell fractions proved negative for onfFN mRNA, whereas its presence in
      thyroid carcinoma was 78/98% (FTC/PTC). Threshold cycle values were calculated
      at: porphobilinogen deaminase (PBGD) = 25.95+/-0.73 (FTC)/24.55+/-5.43 (PTC) (P =
      0.2878); onfFN = 25.48+/-3.15 (FTC)/21.44+/-3.44 (PTC) (*P = 0.0001). Finally,
      onfFN transcripts were detected in blood samples of six out of nine patients with
      known DTC metastases, demonstrating a reliable assay functionality. We propose
      that real-time RT-PCR of onfFN mRNA is superior to other markers in monitoring
      minimal residual disease in DTC with regard to both assay sensitivity and
      specificity.

PMID- 16091758
TI  - Coffee and risk of death from hepatocellular carcinoma in a large cohort study in
      Japan.
AB  - We examined the relation between coffee drinking and hepatocellular carcinoma
      (HCC) mortality in the Japan Collaborative Cohort Study for Evaluation of Cancer
      Risk (JACC Study). In total, 110,688 cohort members (46,399 male and 64,289
      female subjects) aged 40-79 years were grouped by coffee intake into three
      categories: one or more cups per day, less than one cup per day and non-coffee
      drinkers. Cox proportional hazards model by SAS was used to obtain hazard ratio
      of HCC mortality for each coffee consumption categories. The hazard ratios were
      adjusted for age, gender, educational status, history of diabetes and liver
      diseases, smoking habits and alcohol. The hazard ratio of death due to HCC for
      drinkers of one and more cups of coffee per day, compared with non-coffee
      drinkers, was 0.50 (95% confidence interval 0.31-0.79), and the ratio for
      drinkers of less than one cup per day was 0.83 (95% confidence interval 0.54
      1.25). Our data confirmed an inverse association between coffee consumption and
      HCC mortality.

PMID- 16091759
TI  - Cyclin A as a marker for prognosis and chemotherapy response in advanced breast
      cancer.
AB  - We wanted to study cyclin A as a marker for prognosis and chemotherapy response.
      A total of 283 women with metastatic breast cancer were initially enrolled in a
      randomised multicentre trial comparing docetaxel to sequential methotrexate
      fluorouracil (MF) in advanced breast cancer after anthracycline failure. Paraffin
      embedded blocks of the primary tumour were available for 96 patients (34%). The
      proportion of cells expressing cyclin A was determined by immunohistochemistry
      using a mouse monoclonal antibody to human cyclin A. Response evaluation was
      performed according to WHO recommendations. The median cyclin A positivity of
      tumour cells was 14.5% (range 1.2-45.0). Cyclin A correlated statistically
      significantly to all other tested proliferation markers (mitotic count,
      histological grade and Ki-67). A high cyclin A correlated significantly to a
      shorter time to first relapse, risk ratio (RR) 1.94 (95% CI 1.24-3.03) and
      survival from diagnosis, RR 2.49 (95% CI 1.45-4.29), cutoff point for high/low
      proliferation group 10.5%. Cyclin A did not correlate to chemotherapy response or
      survival after anthracycline, docetaxel or MF therapy. Of all tumour biological
      factors tested (mitotic count, histological grade and Ki-67), cyclin A seemed to
      have the strongest prognostic value. Cyclin A is a good marker for tumour
      proliferation and prognosis in breast cancer. In the present study, cyclin A did
      not predict chemotherapy response.

PMID- 16091760
TI  - Capecitabine and mitomycin C as third-line therapy for patients with metastatic
      colorectal cancer resistant to fluorouracil and irinotecan.
AB  - Protracted venous infusion 5-fluorouracil (5FU) combined with mitomycin C (MMC)
      has demonstrated significant activity against metastatic colorectal cancer. Owing
      to potential synergy based upon upregulation of thymidine phosphorylase by MMC,
      the combination of capecitabine and MMC may improve outcomes in irinotecan
      refractory disease. Eligible patients with progressive disease during or within 6
      months of second-line chemotherapy were treated with capecitabine (1250 mg m(-2)
      twice daily) days 1-14 every 3 weeks and MMC (7 mg m(-2) IV bolus) once every 6
      weeks. A total of 36 patients were recruited, with a median age of 64 years
      (range 40-77), and 23 patients (78%) were performance status 0-1. The objective
      response rate was 15.2%. In all, 48.5% of patients had stable disease. Median
      failure-free survival was 5.4 months (95% CI 4.6-6.2). Median overall survival
      was 9.3 months (95% CI: 6.9-11.7). Grade 3 toxicities were palmar-plantar
      erythema 16.7%, vomiting 8.3%, diarrhoea 2.8%, anaemia 8.3%, and neutropenia
      2.8%. No patients developed haemolytic uraemic syndrome. Symptomatic improvement
      occurred for pain, bowel symptoms, and dyspnoea. Capecitabine in combination with
      MMC is an effective regimen for metastatic colorectal cancer resistant to 5FU and
      irinotecan with an acceptable toxicity profile and a convenient administration
      schedule.

PMID- 16091761
TI  - Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression
      of Fas is associated with disease progression.
AB  - The death receptor Fas (Apo1/CD95) and Fas ligand (FasL) system is recognised as
      a major pathway for the induction of apoptosis in vivo, and antiapoptosis via its
      blockade plays a critical role in carcinogenesis and progression in several
      malignancies. However, the function of Fas-FasL system in urothelial cancer (UC)
      has not been elucidated. We therefore investigated the expression of Fas, FasL
      and Decoy receptor 3 for FasL (DcR3) in UC specimens and cell lines, and examined
      the cytotoxic effect of an anti-Fas-activating monoclonal antibody (mAb) in
      vitro. Immunohistochemical examinations of Fas-related molecules were performed
      on 123 UC and 30 normal urothelium surgical specimens. Normal urothelium showed
      Fas staining in the cell membrane and cytoplasm. In UC, less frequent Fas
      expression was significantly associated with a higher pathological grade (P <
      0.0001), a more advanced stage (P = 0.023) and poorer prognosis (P = 0.010). Fas
      and the absence thereof were suggested to be crucial factors with which to select
      patients requiring more aggressive treatment. Moreover, low-dose anti-Fas
      activating mAb sensitised resistant cells to adriamycin, and this synergistic
      effect could be applied in the development of new treatment strategy for UC
      patients with multidrug-resistant tumours.

PMID- 16091762
TI  - Construction of tissue microarrays from prostate needle biopsy specimens.
AB  - Needle biopsies are taken as standard diagnostic specimens for many cancers, but
      no technique exists for the high-throughput analysis of multiple individual
      immunohistochemical (IHC) markers using these samples. Here we present a simple
      and highly reliable technique for constructing tissue microarrays (TMAs) from
      prostatic needle biopsies. Serial sectioning of the TMAs, called 'Checkerboard
      TMAs', facilitated expression analysis of multiple proteins using IHC markers. In
      total, 100% of the analysed biopsies within the TMA both preserved their
      antigenicity and maintained their morphology. Checkerboard TMAs will allow the
      use of needle biopsies (i) alongside other tissue specimens (trans-urethral
      resection of prostates and prostatectomies in the case of prostate cancer) in
      clinical correlation studies when searching for new prognostic markers, and (ii)
      in a diagnostic context for assessing expression of multiple proteins in cancers
      from patients prior to treatment.

PMID- 16091763
TI  - Resistance to tumour challenge after tumour laser thermotherapy is associated
      with a cellular immune response.
AB  - Previous studies in our laboratory have shown that interstitial laser
      thermotherapy (ILT) of an experimental liver tumour is superior to surgical
      excision, at least partly due to a laser-induced immunological effect. The aim of
      the present study was to investigate the time-response relationship of the ILT
      induced immunisation and the cellular response of macrophages and lymphocytes. A
      dimethylhydrazine-induced adenocarcinoma was transplanted into the liver of
      syngeneic rats. Rats with tumour were treated 6-8 days later (tumour size 0.25
      0.40 cm(3)) with ILT of tumour or resection of the tumour-bearing lobe. Two
      groups of rats without tumour were treated with resection of a normal liver lobe
      or ILT of normal liver. A challenging tumour was implanted into the liver of each
      rat 2, 5 or 10 weeks after primary treatment. Rats were killed 6, 12 and 48 days
      (or earlier due to their condition) after challenge (n = 8 in all groups).
      Immunohistochemical techniques were used to determine lymphocytes (CD8, CD4) and
      macrophages (ED1, ED2) in rats having had treatment of a primary tumour.
      Interstitial laser thermotherapy of the first tumour was followed by eradication
      of challenging tumour and absence of tumour spread. This contrasted with rapid
      growth and spread of challenging tumour in the other groups. In the challenging
      vital tumour tissue and in the interface between the tumour and surroundings, the
      number of ED1 macrophages and CD8 lymphocytes was higher in rats having been
      treated with the ILT of tumour than in those having undergone resection of the
      tumour-bearing lobe. The number of ED2 macrophages and CD4 lymphocytes was low
      and did not vary between these two groups. Interstitial laser thermotherapy
      elicited an immune response that eradicated a challenging tumour and was
      associated with increased numbers of tumour-infiltrating macrophages and CD8
      lymphocytes.

PMID- 16091764
TI  - Prognostic significance of osteopontin expression in early-stage non-small-cell
      lung cancer.
AB  - Osteopontin (OPN) is a multifunctional protein, which has recently been shown to
      be linked to tumorigenesis, progression and metastasis in different malignancies.
      Since non-small-cell lung cancer (NSCLC)'s prognosis remains bad, with few
      predictors of outcome, the purpose of this study was to evaluate if OPN might be
      involved in NSCLC's biology and therefore represent a prognostic marker and a
      target for new therapeutic trials. Immunohistochemistry was used to detect OPN
      expression, evaluated as percentage of neoplastic cells with cytoplasmic
      immunoreactivity, in a wide cohort of patients with stage I NSCLC (136 cases).
      The median value of this series (20% of positive cells) was used as the cutoff
      value to distinguish tumours with low (<20%) from tumours with high (> or =20%)
      OPN expression. A statistically significant correlation between high levels of
      OPN and shorter overall (P = 0.034) and disease-free (P = 0.011) survival in our
      patients was shown. Our results support the hypothesis that high OPN expression
      is a significantly unfavourable prognostic factor for the survival of patients
      with stage I NSCLC. This conclusion has notable importance in terms of the
      biological characterization of early-stage tumours and therapeutic opportunities.

PMID- 16091765
TI  - Rapeseed oil, olive oil, plant sterols, and cholesterol metabolism: an ileostomy
      study.
AB  - OBJECTIVE: To study whether olive oil and rapeseed oil have different effects on
      cholesterol metabolism. DESIGN: Short-term experimental study, with controlled
      diets. SETTING: Outpatients at a metabolic-ward kitchen. SUBJECTS: A total of
      nine volunteers with conventional ileostomies. INTERVENTIONS: Two 3-day diet
      periods; controlled diet including 75 g of rapeseed oil or olive oil. MAIN
      OUTCOME MEASURES: Cholesterol absorption, ileal excretion of cholesterol, and
      bile acids. Serum levels of cholesterol and bile acid metabolites. Differences
      between diets evaluated with Wilcoxon's signed rank sum test. RESULTS: Rapeseed
      oil diet contained 326 mg more plant sterols than the olive oil diet. Rapeseed
      oil tended to decrease cholesterol absorption by 11% (P = 0.050), and increased
      excretion of cholesterol, bile acids, and their sum as sterols by 9% (P = 0.021),
      32% (P = 0.038), and 51% (P = 0.011) compared to olive oil. A serum marker for
      bile acid synthesis (7alpha-hydroxy-4-cholesten-3-one) increased by 28% (P =
      0.038) within 10 h of consumption, and serum cholesterol levels decreased by 7%
      (P = 0.024), whereas a serum marker for cholesterol synthesis (lathosterol) as
      well as serum levels of plant sterols remained unchanged. CONCLUSIONS: Rapeseed
      oil and olive oil have different effects on cholesterol metabolism. Rapeseed oil,
      tends to decrease cholesterol absorption, increases excretion of cholesterol and
      bile acids, increases serum marker of bile acid synthesis, and decreases serum
      levels of cholesterol compared to olive oil. This could in part be explained by
      different concentrations of natural plant sterols. SPONSORSHIP: Supported by the
      Goteborg Medical Society, the Swedish Medical Society, the Swedish Board for
      Agricultural Research (SJFR) grant 50.0444/98 and by University of Goteborg.

PMID- 16091766
TI  - Antioxidant supplementation enhances antioxidant capacity and mitigates oxidative
      damage following acute ischaemic stroke.
AB  - OBJECTIVE: To test whether supplementary antioxidants immediately following acute
      ischaemic stroke will enhance antioxidant capacity and mitigate oxidative damage.
      DESIGN: A randomised controlled trial. SETTING: A university teaching hospital.
      SUBJECTS: A total of 48 acute ischaemic stroke patients within 12 h of symptom
      onset. INTERVENTION: Daily oral 800 IU (727 mg) of alpha-tocopherol and 500 mg of
      vitamin C (n = 24), or no treatment (n = 24) for 14 days. Treatment group and
      controls were matched for stroke subtype and age. MAIN OUTCOME MEASURES: alpha
      Tocopherol, ascorbic acid, total antioxidant capacity (TAOC), plasma
      malondialdehyde (MDA) and C-reactive protein (CRP) before treatment, at day 7 and
      day 14 following recruitment. RESULTS: In all, 14 days of vitamin supplementation
      significantly improved plasma alpha-tocopherol and ascorbic concentrations in the
      treatment group compared with the decrease seen in the control group (P < 0.005
      for difference in cumulative changes). TAOC increased significantly in the
      treatment group compared with controls (P < 0.003). There was a significant
      reduction in plasma MDA concentration in the treatment group, in contrast to the
      increase seen in the control group (P < 0.002). After adjusting for clinical
      complications CRP concentrations within 90 days postinfarct were significantly
      lower in the treatment group compared with controls. CONCLUSION: Supplementation
      with antioxidant vitamins within 12 h of onset of acute ischaemic stroke
      increased antioxidant capacity, reduced lipid peroxidation products and may have
      an anti-inflammatory effect. SPONSORSHIP: Sheffield Teaching Hospital NHS Trust.

PMID- 16091767
TI  - Physical activity, energy expenditure and their correlates in two cohorts of
      Swedish subjects between adolescence and early adulthood.
AB  - OBJECTIVE: To assess physical activity and energy expenditure and to identify
      their correlates during adolescence and early adulthood. DESIGN: In a cohort
      study, total energy expenditure (TEE) and physical activity level (PAL) were
      assessed at 15 and 21 y from a 7-day activity diary and predicted BMR. The
      influences on TEE and PAL of body size, gender, sexual maturity, physical
      activity habits, sitting time, region, social conditions, employment, food
      habits, smoking and alcohol intake were examined in multivariate analyses.
      SUBJECTS: 71 male and 89 female subjects, living in two socioeconomically
      different regions of Sweden, a university region and an industrial region.
      SETTING: The university city of Uppsala and the industrial town of Trollhattan.
      RESULTS: At both 15 and 21 y, PAL and TEE were high, with gender, sitting time
      and physical activity habits as main correlates. At age 21 y, employment and the
      mother's educational level also appeared as significant correlates. The relations
      between the main variables and their correlates were more complex than at age 15
      y, and the sitting time was reduced and the activity habits were changed.
      CONCLUSIONS: A reduction of daily sitting appears to be a major reason why high
      levels of physical activity and energy expenditure were maintained from 15 to 21
      y of age in spite of changed and less frequent activity habits during this
      interval.

PMID- 16091768
TI  - Colonization of Phaseolus vulgaris nodules by Agrobacterium-like strains.
AB  - Non-nodulating Agrobacterium-like strains identified among root nodule isolates
      of common bean were labeled with gusA, a reporter gene encoding beta
      glucuronidase (GUS). Bean plants were then co-inoculated with an infective
      Rhizobium strain and labeled transconjugants of Agrobacterium-like strains. Blue
      staining of nodules showed that Agrobacterium-like strains were able to colonize
      these symbiotic organs. Isolation and characterization by restriction fragment
      length polymorphism analysis of PCR-amplified 16S rRNA genes revealed a mixed
      population of Rhizobium and Agrobacterium-like strains in all nodules showing GUS
      activity. PCR amplification of the nifH gene and nodulation tests did not show
      any evidence of acquisition of symbiotic gene by lateral transfer from Rhizobium
      to Agrobacterium-like strains. Moreover, these strains were able to invade mature
      nodules. Based on sequencing of the 16S rRNA gene, one of these Agrobacterium
      like strains showed 99.4% sequence similarity with Agrobacterium bv. 1 reference
      strains and 99% similarity with an Agrobacterium bv. 1 strain isolated from
      Acacia mollisima in Senegal. Agrobacterium tumefaciens C58 and the disarmed
      variant AT123 did not show any ability to colonize nodules. Co-inoculation of
      bean seeds with Agrobacterium and Rhizobium strains did not enhance nodulation
      and plant yield under controlled conditions.

PMID- 16091769
TI  - Intrastrain internal transcribed spacer heterogeneity in Ganoderma species.
AB  - Intrastrain internal transcribed spacer (ITS) heterogeneity is first reported
      from Ganoderma, a fungal genus within Basidiomycetes. ITS amplification products
      from 4 strains, representing 4 Ganoderma species, were cloned and sequenced. Two
      to five different ITS types were found within a single strain. The clone
      sequences were analyzed along with other sequences from Ganoderma retrieved from
      GenBank. The results show that sequence variation within strains varies
      considerably with species and the heterogeneity may occur in the 3 parts (ITS1,
      ITS2, and 5.8S) of the ITS region.

PMID- 16091770
TI  - Biological control of collar rot disease with broad-spectrum antifungal bacteria
      associated with groundnut.
AB  - Bacteria associated with 6 habitats of groundnut were evaluated for their broad
      spectrum antifungal activity and suppression of collar rot (Aspergillus niger) of
      groundnut. Three hundred and ninety-three strains were tested against 8 fungal
      pathogens of groundnut including 5 necrotrophic fungi, Aspergillus flavus, A.
      niger, Rhizoctonia bataticola, Rhizoctonia solani, and Sclerotium rolfsii, and 3
      biotrophic fungi, Cercospora arachidicola, Phaeoisariopsis personata, and
      Puccinia arachidis. Pseudomonas sp. GRS 175, Pseudomonas aeruginosa GPS 21, GSE
      18, GSE 19, and GSE 30, and their cell-free culture filtrates were highly
      antagonistic to all the test fungi. The cell-free culture filtrates of these
      bacteria were fungicidal and induced mycelial deformations including hyphal
      bulging and vacuolization in necrotrophic fungi. The cell-free culture filtrates
      at 10% (v/v) concentration significantly inhibited the spore germination of
      biotrophic fungi. In the greenhouse, P. aeruginosa GSE 18 emerged as an effective
      biocontrol agent of collar rot closely followed by P. aeruginosa GSE 19. The
      bacterium applied as a seed treatment reduced the pre-emergence rotting and
      postemergence wilting by > 60%. Pseudomonas aeruginosa GSE 18 effectively
      colonized the groundnut rhizosphere, both in native and in A. niger infested
      potting mixtures. Ninety-day-old peat formulation of P. aeruginosa GSE 18 had
      biocontrol ability comparable with the midlog-phase cells. Pseudomonas aeruginosa
      GSE 18, tolerant to thiram, in combination with the fungicide had an improved
      collar rot control. The present study was a successful attempt in selection of
      broad-spectrum and fungicide tolerant biocontrol agents that can be a useful
      component of integrated management of collar rot.

PMID- 16091771
TI  - Inhibitory effect of sodium fluoride and chlorhexidine on the growth of oral
      lactobacilli.
AB  - The accumulation of microorganisms in dental plaque is related to the etiology of
      caries and periodontal disease, with a high prevalence worldwide. The
      prophylactic measures include the use of chemical agents as NaF and
      chlorhexidine. Lactic acid bacteria are members of the normal microbiota of the
      oral cavity being discussed with regard to their beneficial or detrimental effect
      in this environment. The present study was performed to determine the growth of
      some species of Lactobacillus at different concentrations of NaF and
      chlorhexidine. The strains were isolated from both caries-free and caries
      patients. Their growth parameters were evaluated by the application of the
      Gompertz model to the experimental data of optical density as a measurement of
      growth. The degree of inhibition of the growth of all of the lactobacilli studied
      was different, depending on each particular strain. NaF at 1 mmol x L(-1)
      inhibited between 5% and 46%, at 5 mmol x L(-1) between 13% and 65%, and at 20
      mmol x L(-1) between 57% and 84%. CHX at higher concentrations (197 and 98 mmol x
      L(-1) showed a complete inhibition of some of the strains. The significance of
      the results was evaluated by the application of a multivariate analysis and also
      compared with the inhibition of pathogenic Streptococcus mutans and with
      lactobacilli strains from collection cultures.

PMID- 16091772
TI  - Novel antibacterial proteins from entomocidal crystals of Bacillus thuringiensis
      ssp. israelensis.
AB  - Proteins with molecular masses of 36 and 34 kDa (Bti36 and Bti34) were isolated
      from entomocidal crystals formed by Bacillus thuringiensis ssp. israelensis
      cells. The samples of Bti36 contained the admixture of a protein with a molecular
      mass of 33 kDa (Bti33), apparently a product of proteolysis of Bti36. These 3
      proteins are significantly different in N-terminal sequences from known delta
      endotoxins of B. thuringiensis and show antibacterial activity toward Micrococcus
      luteus. The combination of Bti36 and Bti33 also suppresses the growth of some
      other microorganisms including Streptomyces chrysomallus. The effects of the
      mixture of Bti36 and Bti33 on the M. luteus cell surface and on the surface of S.
      chrysomallus cells and exospores are similar, but they are different from the
      effect of endotoxin Cry11A on micrococcal cells.

PMID- 16091773
TI  - Characterization of aerobic and anaerobic vegetative growth of the food-borne
      pathogen Bacillus cereus F4430/73 strain.
AB  - The Gram-positive bacterium Bacillus cereus is a facultative anaerobe that is
      still poorly characterized metabolically. In this study, the aerobic vegetative
      growth and anaerobic vegetative growth of the food-borne pathogen B. cereus
      F4430/73 strain were compared with those of the genome-sequenced ATCC14579 strain
      using glucose and glycerol as fermentative and nonfermentative carbon sources,
      respectively. Uncontrolled batch cultures on several defined media showed that B.
      cereus strains had high amino acid or pyruvate requirements for anaerobic
      fermentative growth. In addition, growth performance was considerably improved by
      maintaining the pH of the culture medium near neutrality. Spectra of fermentation
      by-products were typically (per mole of glucose) 0.2-0.4 acetate, 1.1-1.4 L
      lactate, 0.3-0.4 formate, and 0.05-0.2 ethanol with only traces of succinate,
      pyruvate, and 2,3-butanediol. These spectra were drastically changed in the
      presence of 20 mmol nitrate x L(-1), which stimulated anaerobic growth. During
      anaerobic and aerobic respiration, the persistent production of acetate and other
      by-products indicated overflow metabolisms. This was especially true in glucose
      grown cells for which respiratory complex III made only a minor contribution to
      growth. Surprisingly, oxygen uptake rates linked to the cytochrome c and quinol
      branches of the respiratory chain were maintained at high levels in anaerobic,
      respiring, or fermenting cells. Growth and metabolic features of B. cereus
      F4430/73 are discussed using biochemical and genomic data.

PMID- 16091774
TI  - Genetic differentiation of charcoal rot pathogen, Macrophomina phaseolina, into
      specific groups using URP-PCR.
AB  - Forty isolates of Macrophomina phaseolina, a pathogen causing charcoal dry root
      rot of soybean, cotton, and chickpea, were genetically characterized with
      universal rice primers (URP; primers derived from DNA repeat sequences in the
      rice genome) using polymerase chain reaction (URP-PCR). Out of 12 URPs used in
      this study, 5 primers were effective in producing polymorphic fingerprint
      patterns from the DNA of M. phaseolina isolates. Three primers (URP-2F, URP-6R,
      and URP-30F) were quite informative and produced high levels of polymorphism
      among the isolates of M. phaseolina. Analysis of the entire fingerprint profiles
      using unweighted pair-group method with arithmetic averages (UPGMA) clearly
      differentiated M. phaseolina isolates obtained from soybean, cotton, and chickpea
      hosts into specific groups. In this study, we found for the first time
      transferability and use of PCR primers derived from plant genomes to generate
      host-specific fingerprint profiles of M. phaseolina, a broad host range plant
      pathogenic fungus. These results demonstrate that URPs are sensitive and
      technically simple to use for assaying genetic variability in M. phaseolina
      populations.

PMID- 16091775
TI  - Expression of the cry11A gene of Bacillus thuringiensis ssp. israelensis in
      Saccharomyces cerevisiae.
AB  - The complete cry11A region gene of Bacillus thuringiensis ssp. israelensis was
      fused in frame to the 3' end of the GST gene under the control of the
      Saccharomyces cerevisiae HXK1 promoter. The fusion protein GST-cry11A was
      expressed in S. cerevisiae strain AMW13C+. The fusion gene GST-cry11A was
      expressed when yeast cells were grown on galactose and a nonfermentable medium
      containing ethanol as carbon and energy source. When the cells were grown in
      glucose, mannose, fructose, or glycerol as carbon sources, the GST-cry11A gene
      was repressed. Thus, a regulated expression in accordance with the regulatory
      activity of the HXK1 gene promoter has been detected. The GST-cry11A fusion
      protein was detected in the transformed yeasts as a soluble protein. The fusion
      protein was purified by affinity chromatography using glutathione-Sepharose
      beads. Cell-free extracts from transformed yeasts grown in ethanol-containing
      culture media showed insecticidal activity against third-instar Aedes aegypti
      larvae. This insecticidal activity was increased about 4-fold when the purified
      fusion protein was assayed.

PMID- 16091776
TI  - Purification and characterization of an intracellular aspartyl acid proteinase
      (pumAi) from Ustilago maydis.
AB  - The intracellular proteinase pumAi in Ustilago maydis has been associated with
      yeast-mycelium dimorphic transition. The proteinase was purified from a cell-free
      extract by ammonium sulfate fractionation and chromatographic steps including
      hydrophobic interactions on a Phenyl Superose column, ion exchange on a Mono Q
      column, and gel filtration on Superose 12 columns. The enzyme has a mass of 35.3
      36.6 kDa, a pH and temperature optimum of 4.0 and 40 degrees C, respectively, and
      a pI of 5.5. The enzyme degraded hemoglobin, gelatin, albumin, and casein, but
      not collagen, and the enzymatic activity was strongly inhibited by pepstatin A,
      an aspartyl proteinase-specific inhibitor. The biochemical characteristics of
      pumAi are similar to other fungal intracellular aspartyl proteinases, however,
      this is the first biochemical characterization of a basidiomycete proteinase
      probably associated with dimorphic yeast-mycelium transition.

PMID- 16091777
TI  - Overproduction and characterization of xylanase B from Aspergillus niger.
AB  - The xynB gene, which encodes endo-beta-1,4-xylanase XynB, in Aspergillus niger
      BRFM281 was amplified by RT-PCR using mRNA isolated from a culture containing
      sugar beet pulp as an inducer. The cDNA was cloned into an expression cassette
      under the control of the strong and constitutive glyceraldhehyde-3-phosphate
      dehydrogenase gene promoter. The expression system was designed to produce the
      recombinant enzyme XynB with a six-histidine peptide fused to the carboxy end of
      the protein. Homologous overproduction of XynB was successfully achieved in shake
      flask cultures, and the secretion yield was estimated to be 900 mg x L(-1). The
      recombinant XynB was purified 1.5-fold by immobilized metal affinity
      chromatography to homogeneity using a one-step purification protocol with 71%
      recovery. The purified recombinant enzyme was fully characterized and has a
      molecular mass of 23 kDa and an optimal activity at pH 5.5 and 50 degrees C with
      stability in the pH range 4.0-7.0 and temperature up to 50 degrees C. Using
      soluble oat spelts xylan, the determined Km and Vmax values were 7.1 mg x mL(-1)
      and 3881 U x mg(-1), respectively.

PMID- 16091778
TI  - Serial passage of the opportunistic pathogen Aspergillus flavus through an insect
      host yields decreased saprobic capacity.
AB  - To study the early stages of the effect of host restriction on pathogen
      evolution, we subjected the opportunistic fungus Aspergillus flavus to a serial
      propagation scheme, whereby insect-virulent conidia were selected for repeated
      passage through an insect host (Galleria mellonella larvae) for 5 generations. Of
      the 35 lineages promulgated through this scheme, there were no consistent changes
      in virulence, which was measured by percent mortality of the larvae. There were,
      however, increases in the number of conidia on the insect cadavers (9 of 35
      lineages) and decreases in the number of days between death and the appearance of
      fungal growth on the cadavers (4 of 35 lineages). Notably, most of the lineages
      (28 of 35 lineages) demonstrated a statistically significant decrease in the
      diameter of the colonies subcultured onto artificial media, indicating a
      decreased ability to grow saprobically. Conversely, most of the A. flavus
      cultures successively grown on agar media (9 of 10 lineages) exhibited no change
      in colony diameter after 15 rounds of subculturing. Propagation of the
      opportunist A. flavus through the insect host G. mellonella resulted in a
      diminished capacity to grow on an alternate substrate, while maintaining or
      increasing its ability to use the host as a nutrient supply.

PMID- 16091779
TI  - Potential application for mesenchymal stem cells in the treatment of
      cardiovascular diseases.
AB  - Stem cells isolated from various sources have been shown to vary in their
      differentiation capacity or pluripotentiality. Two groups of stem cells,
      embryonic and adult stem cells, may be capable of differentiating into any
      desired tissue or cell type, which offers hope for the development of therapeutic
      applications for a large number of disorders. However, major limitations with the
      use of embryonic stem cells for human disease have led researchers to focus on
      adult stem cells as therapeutic agents. Investigators have begun to examine
      postnatal sources of pluripotent stem cells, such as bone marrow stroma or
      adipose tissue, as sources of mesenchymal stem cells. The following review
      focuses on recent research on the use of stem cells for the treatment of
      cardiovascular and pulmonary diseases and the future application of mesenchymal
      stem cells for the treatment of a variety of cardiovascular disorders.

PMID- 16091780
TI  - Regulation of calcium-activated chloride channels in smooth muscle cells: a
      complex picture is emerging.
AB  - Calcium-activated chloride channels (ClCa) are ligand-gated anion channels as
      they have been shown to be activated by a rise in intracellular Ca2+
      concentration in various cell types including cardiac, skeletal and vascular
      smooth muscle cells, endothelial and epithelial cells, as well as neurons.
      Because ClCa channels are normally closed at resting, free intracellular Ca2+
      concentration (approximately 100 nmol/L) in most cell types, they have generally
      been considered excitatory in nature, providing a triggering mechanism during
      signal transduction for membrane excitability, osmotic balance, transepithelial
      chloride movements, or fluid secretion. Unfortunately, the genes responsible for
      encoding this class of ion channels is still unknown. This review centers
      primarily on recent findings on the properties of these channels in smooth muscle
      cells. The first section discusses the functional significance and biophysical
      and pharmacological properties of ClCa channels in smooth muscle cells, and ends
      with a description of 2 candidate gene families (i.e., CLCA and Bestrophin) that
      are postulated to encode for these channels in various cell types. The second
      section provides a summary of recent findings demonstrating the regulation of
      native ClCa channels in vascular smooth muscle cells by calmodulin-dependent
      protein kinase II and calcineurin and how their fine tuning by these enzymes may
      influence vascular tone.

PMID- 16091781
TI  - The effects of the insulin-like growth factor-I aptamer, NBI-31772, on glucose
      homeostasis in the mouse.
AB  - The majority of insulin-like growth factor-I (IGF-I) in the adult rodent
      circulation is bound to high affinity IGF binding proteins. We investigated the
      changes in IGF-I clearance, blood glucose and plasma insulin levels, and tissue 2
      deoxyglucose uptake after intravenous administration of the IGF aptamer, NBI
      31772, which selectively competes with IGF-I for binding to the IGFBPs, but has
      no effect at the IGF-I receptor. Clearance of 125I-IGF-I was significantly
      increased in NBI-31772-treated mice compared with vehicle-treated mice (t1/2 =
      45.0 +/- 1.9 vs. 56.3 +/- 3.9 min, respectively; p = 0.021). However, NBI-31772
      had no significant effect on glucose levels, and no insulin sparing effect was
      apparent neither under basal conditions nor during an intravenous glucose
      challenge. The decline in the specific activity after 3H-2-deoxyglucose
      administration was significantly less rapid in NBI-31772-treated mice compared
      with controls, suggesting that the IGF-I aptamer had an inhibitory effect on
      hepatic gluconeogenesis. In contrast, no insulin-like effect was apparent in
      other tissues examined. 3H-2-deoxyglucose accumulation was similar in all tissues
      analyzed, including skeletal muscle, which is thought to be particularly
      sensitive to IGF-I. These data suggest that the IGF-I aptamer affects clearance
      of radiolabeled IGF-I from the circulation, but has no marked effects on glucose
      nor insulin homeostasis. The search for hydrophilic IGF aptamers with longer
      duration of action that could be used in the treatment of diabetes may be
      rewarding.

PMID- 16091782
TI  - Functional expression and cellular localization of the Na+/H+ exchanger Sod2 of
      the fission yeast Schizosaccharomyces pombe.
AB  - In the fission yeast Schizosaccharomyces pombe, the Na+/H+ exchanger, Sod2, plays
      a major role in the removal of excess intracellular sodium, and its disruption
      results in a sodium-sensitive phenotype. We examined the subcellular distribution
      and dynamics of Sod2 expression in S. pombe using a sod2-GFP fusion protein under
      the control of an attenuated version of the inducible nmt promoter. Sod2 was
      localized throughout the plasma membrane, the nuclear envelope, and some internal
      membrane systems. In exponentially growing cells, in which sod2-GFP was expressed
      and then the promoter turned-off, previously synthesized sod2-GFP was stable for
      long periods and found localized to the plasma membrane in the medial regions of
      the cell. It was not present at the actively growing cell ends. This suggests
      that these regions of the cell contain old plasma membrane protein vs. newly
      synthesized plasma membrane without Sod2 at the growing ends. Sod2 localization
      was not affected by salt stress. The results suggest that Sod2 is both a plasma
      membrane protein and is present in intracellular membranes. It is likely tethered
      within discrete regions of the plasma membrane and is not free to diffuse
      throughout the bilayer.

PMID- 16091783
TI  - Characterization of [3H]-forskolin binding sites in young and adult rat brain
      cortex: identification of suramin as a competitive inhibitor of [3H]-forskolin
      binding.
AB  - Little is know about forskolin binding in the rat brain during ontogenetic
      development. For this paper, we have characterized specific binding sites for
      [3H]-forskolin in cerebrocortical membranes from young (12-day-old) and adult (90
      day-old) rats. High-affinity, as well as super-high-affinity, [3H]-forskolin
      binding sites were detected in samples from both age groups tested, and the
      binding parameters of these sites differed significantly. Whereas the number of
      high-affinity [3H]-forskolin binding sites was higher by about 50% in adult than
      in young rats, their affinity was markedly (about 4 times) lower. In the presence
      of AlF4-, the number high-affinity [3H]-forskolin binding sites in samples from
      young rats rose to the level determined in samples from adult animals, and the
      number of super-high-affinity sites considerably increased in both age groups.
      The different characteristics of [3H]-forskolin binding found in cerebrocortical
      membranes from young and adult rats may be closely related to markedly diminished
      adenyl cyclase activity in preparations from adult animals. Results of our
      experiments with suramin indicated that this drug may act as a competitive
      inhibitor of [3H]-forskolin binding.

PMID- 16091784
TI  - Homocysteine-dependent cardiac remodeling and endothelial-myocyte coupling in a 2
      kidney, 1 clip Goldblatt hypertension mouse model.
AB  - Accumulation of interstitial collagen (fibrosis) between the endothelium and
      myocytes is one of the hallmarks of cardiac failure in renovascular hypertension
      (RVH). Renal insufficiency increases plasma homocysteine (Hcy), and levels of
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma) are inversely
      related to plasma Hcy levels. We hypothesize that in RVH, accumulation of
      collagen between the endothelium and myocytes leads to endothelial-myocyte
      disconnection and uncoupling, in part, by hyperhomocysteinemia. Furthermore, we
      hypothesize that Hcy increases reactive oxygen species, generates nitrotyrosine,
      activates latent matrix metalloproteinase, and decreases the levels of
      endothelial nitric oxide in response to antagonizing PPAR-gamma. To create RVH in
      mice, the left renal artery was clipped with 0.4-mm silver wire for the 2 kidney,
      1 clip (2K1C) method. Sham surgery was used as a control. To induce PPAR-gamma, 8
      microg/mL ciglitazone (CZ) was administered to drinking water 2 days before
      surgery and continued for 4 weeks. Mice were grouped as 2K1C, sham, 2K1C+CZ, or
      sham+CZ (n = 6 in each group). Plasma Hcy increased 2-fold in the 2K1C-treated
      group (p < 0.05) as compared with the sham, and CZ had no effect on Hcy levels as
      compared to the 2K1C-treated group. Hcy binding in cardiac tissue homogenates
      decreased in the 2K1C-treated group but was substantially higher in the CZ
      treated group. Cardiac reactive oxygen species levels were increased and
      endothelial nitric oxide were decreased in the 2K1C-treated group. Matrix
      metalloproteinase-2 and -9 activities were increased in the 2K1C-treated group
      compared with the control. Levels of cardiac inhibitor of metalloproteinase were
      decreased, whereas there was no change in tissue inhibitor of metalloproteinase-1
      expression in the 2K1C-treated group vs. the sham-treated group. Collagen and
      nitrotyrosine levels were increased in the 2K1C-treated group, but mice treated
      with CZ showed lower levels comparatively. Cardiac transferase deoxyuridine nick
      end labeling-positive cells were increased, and muscle cells were impaired in the
      2K1C-treated mice vs. the sham-control mice. This was associated with decreased
      acetylcholine and bradykinin responses, which suggests endothelial-myocyte
      uncoupling in 2K1C-treated mice. Our results suggest that fibrosis between the
      endothelium and myocytes leads to an endothelial-myocyte disconnection and
      uncoupling by Hcy accumulation secondary to increased reactive oxygen species,
      nitrotyrosine, matrix metalloproteinase, and decreased endothelial nitric oxide
      in response to antagonizing PPAR-gamma.

PMID- 16091785
TI  - Endogenous prolactin modulated the calcium absorption in the jejunum of suckling
      rats.
AB  - Prolactin has been reported to stimulate intestinal calcium absorption in young
      and mature, but not aging rats. The present study was performed on suckling rats
      to elucidate the actions of endogenous prolactin on calcium absorption in various
      intestinal segments. Before measuring the calcium fluxes, 9-day-old rats were
      administered for 7 days with 0.9% NaCl, s.c. (control), 3 mg/kg bromocriptine,
      i.p., twice daily to abolish secretion of endogenous prolactin, or bromocriptine
      plus exogenous 2.5 mg/kg prolactin, s.c. Thereafter, the 16-day-old rats were
      experimented upon by instilling the 45Ca-containing solution into the intestinal
      segments. The results showed that, under a physiological condition, the jejunum
      had the highest rate of calcium absorption compared with other segments (1.4 +/-
      0.35 micromol.h-1.cm-1, p < 0.05). The duodenum and ileum also manifested calcium
      absorption, whereas the colon showed calcium secretion. Lack of endogenous
      prolactin decreased lumen-to-plasma and net calcium fluxes in jejunum from 2.07
      +/- 0.31 to 1.19 +/- 0.12 and 1.40 +/- 0.35 to 0.88 +/- 0.18 micromol.h-1.cm-1 (p
      < 0.05), respectively, and exogenous prolactin restored the jejunal calcium
      absorption to the control value. Endogenous prolactin also had an effect on the
      duodenum but, in this case, exogenous prolactin did not reverse the effect of
      bromocriptine. However, neither ileal nor colonic calcium fluxes were influenced
      by prolactin. Because luminal sodium concentration has been demonstrated to
      affect calcium absorption in mature rats, the effect of varying luminal sodium
      concentrations on calcium fluxes in suckling rats was evaluated. The jejunum was
      used due to its highest rate of calcium absorption. After filling the jejunal
      segments with 124 (control), 80, 40 mmol/L Na+-containing or Na+-free solution,
      increases in calcium absorption were found to be inversely related to luminal
      sodium concentrations in both control and bromocriptine-treated rats. The plasma
      concentration of 45Ca under luminal sodium free condition was also higher than
      that of the control condition (2.26% +/- 0.07% vs. 2.01% +/- 0.09% administered
      dose, p < 0.05). However, 3H-mannitol, a marker of the widening of tight junction
      that was introduced into the lumen, had a stable level in the plasma during an
      increase in plasma 45Ca, suggesting that the widening of tight junction was not
      required for enhanced calcium absorption. In conclusion, calcium absorption in
      suckling rats was of the highest rate in the jejunum where endogenous prolactin
      modulated calcium absorption without increasing the paracellular transport of
      mannitol.

PMID- 16091786
TI  - Expression of proteinase-activated receptor 2 on human primary gastrointestinal
      myofibroblasts and stimulation of prostaglandin synthesis.
AB  - It is known that subepithelial myofibroblast-derived prostaglandin (PG)E2 can
      regulate intestinal epithelial cell functions, and that proteinase-activated
      receptor-2 (PAR2) is abundantly expressed in the gastrointestinal tract. Since
      PAR2 activation has previously been associated with stimulation of PGE2
      synthesis, we hypothesized that PAR2 expressed on primary human gastrointestinal
      myofibroblasts regulates PGE2 synthesis via cyclooxygenase (COX)-1 and (or) COX
      2, and associated PGE synthases. Primary human myofibroblasts were isolated from
      the resection tissue of the esophagus, small intestine, and colon. Expression of
      functional PAR2 was determined by RT-PCR and by calcium mobilization in Fura-2/AM
      loaded cells. Trypsin and the selective PAR2-activating peptide (PAR2-AP) SLIGRL
      NH2 stimulated PGE2 synthesis in a concentration-dependent manner, as measured by
      enzyme immunoassay. Selective COX inhibition showed PAR2-induced PGE2 synthesis
      to be COX-1 dependent in esophageal myofibroblasts and both COX-1 and COX-2
      dependent in colonic cells, consistent with the distribution of COX-1 and COX-2
      expression. Although both cytosolic and microsomal PGE synthases were expressed
      in cells from all tissues, microsomal PGE synthases were expressed at highest
      levels in the colonic myofibroblasts. Activation of PAR2 on gastrointestinal
      myofibroblasts stimulates PGE2 synthesis via different pathways in the colon than
      in the esophagus and small intestine.

PMID- 16091787
TI  - Effects of hydrochlorothiazide and propranolol treatment on chylomicron
      metabolism in hypertensive objects.
AB  - Modifications in chylomicron metabolism caused by antihypertensive drugs were
      investigated in hypertensive subjects because previous studies had indicated that
      diuretics and beta-blockers modify the plasma lipid concentrations through
      mechanisms that were not fully understood. A triglyceride-rich emulsion
      resembling lymph chylomicrons, labeled with (3H) triolein and (14C) cholesteryl
      oleate, was infused intravenously into mildly hypertensive patients after 8 weeks
      on placebo and subsequently on hydrochlorothiazide (n = 10) or propranolol (n =
      8). The residence time of both radioactivities in plasma was utilized for the
      simultaneous calculation of the particle remnant removal rate and of the
      lipoprotein lipase activity expressed as a delipidation index = 1 - [(3H)
      triolein residence time/(14C) cholesteryl oleate residence time]. Treatment with
      hydrochlorothiazide diminished the delipidation rate value whereas propranolol
      mildly increased the removal rate of the remnant particle. These alterations of
      the chylomicron kinetics were not accompanied by changes in plasma triglycerides,
      glucose, and insulin concentration as measured in the fasting state. The
      impairment of the lipoprotein lipase activity by thiazides and the faster removal
      rate of the whole particle by propranolol could explain the reason why in
      previous clinical studies the simultaneous use of these drugs does not aggravate
      the hyperlipidemia known to be induced by thiazides alone.

PMID- 16091788
TI  - Effects of human pregnancy and aerobic conditioning on alveolar gas exchange
      during exercise.
AB  - This study examined the effects of aerobic conditioning during the second and
      third trimesters of human pregnancy on ventilatory responses to graded cycling.
      Previously sedentary pregnant women were assigned randomly to an exercise group
      (n = 14) or a nonexercising control group (n = 14). Data were collected at 15-17
      weeks, 25-27 weeks and 34-36 weeks of pregnancy. Testing involved 20 W.min-1
      increases in work rate to a heart rate of 170 beats.min-1 and (or) volitional
      fatigue. Breath-by-breath ventilatory and alveolar gas exchange measurements were
      compared at rest, a standard submaximal .VO2 and peak exercise. Within both
      groups, resting .V(E), .V(A), and V(T)/T(I) increased significantly with
      advancing gestation. Peak work rate, O2 pulse (.VO2/HR), .V(E), .V(A) respiratory
      rate, V(T)/T(I), .VO2, .VCO2, and the ventilatory threshold (T(vent)) were
      increased after physical conditioning. Chronic maternal exercise has no
      significant effect on pregnancy-induced changes in ventilation and (or) alveolar
      gas exchange at rest or during standard submaximal exercise. Training-induced
      increases in T(vent) and peak oxygen pulse support the efficacy of prenatal
      fitness programs to improve maternal work capacity.

PMID- 16091789
TI  - Effect of various antagonists on the Channa striatus fillet extract
      antinociception in mice.
AB  - The effects of an aqueous supernatant of haruan (ASH) (Channa striatus) fillet
      extract on various antinociception receptor system activities were examined using
      a mouse abdominal-constriction model. Mice that were pretreated with distilled
      water, s.c., followed 10 min later by administration of 25%, 50%, and 100%
      concentration ASH, s.c., produced a significant concentration-dependent
      antinociceptive activity (p < 0.001). Pretreatment with naloxone (0.3, 1.0, and
      3.0 mg/kg body mass), 10 min before ASH administration, failed to block the
      extract antinociception. Pretreatment of the 100% concentration ASH with
      mecamylamine (5 mg/kg), pindolol (10 mg/kg), and haloperidol (1 mg/kg) also did
      not cause any significant change in its antinociception. However, pretreatment
      with atropine (5 mg/kg), bicuculline (10 mg/kg), phenoxybenzamine (10 mg/kg), and
      methysergide (5 mg/kg) were found to reverse ASH antinociception. Based on the
      above findings, the ASH is suggested to contain different types of bioactive
      compounds that act synergistically on muscarinic, GABAA, alpha-adrenergic, and
      serotonergic receptor systems to produce the observed antinociception.

PMID- 16091790
TI  - Metabolic and sarcoplasmic reticulum Ca2+ cycling responses in human muscle 4
      days following prolonged exercise.
AB  - This study investigated the effects of prolonged exercise on muscle sarcoplasmic
      reticulum (SR) Ca2+ cycling properties and the metabolic responses with and
      without a session of exercise designed to reduce muscle glycogen reserves while
      on a normal carbohydrate (CHO) diet. Eight untrained males (VO(2peak) = 3.81 +/-
      0.12 L/min, mean +/- SE) performed a standardized cycle-to-fatigue at 55%
      VO(2peak) while on a normal CHO diet (Norm CHO) and 4 days following prolonged
      exercise while on a normal CHO diet (Ex+Norm CHO). Compared to rest, exercise in
      Norm CHO to fatigue resulted in significant reductions (p < 0.05) in Ca2+ uptake
      (3.17 +/- 0.21 vs. 2.47 +/- 0.12 micromol.(g protein)-1.min-1), maximal Ca2+
      ATPase activity (Vmax, 152 +/- 12 vs. 119 +/- 9 micromol.(g protein)-1.min-1) and
      both phase 1 (15.1 +/- 0.98 vs. 13.1 +/- 0.28 micromol.(g protein)-1.min-1) and
      phase 2 (6.56 +/- 0.33 vs. 4.91 +/- 0.28 micromol.(g protein)-1.min-1) Ca2+
      release in vastus lateralis muscle. No differences were observed between Norm CHO
      and Ex-Norm CHO in the response of these properties to exercise. Compared with
      Norm CHO, Ex+Norm CHO resulted in higher (p < 0.05) resting Ca2+ uptake (3.17 +/-
      0.21 vs. 3.49 +/- 0.24 micromol.(g protein).min-1 and higher ionophore ratio,
      defined as the ratio of Vmax measured with and without the Ca2+-ionophore A23187,
      (2.3 +/- 0.3 vs. 4.4 +/- 0.3 micromol.(g protein).min-1) at fatigue. No
      differences were observed between conditions in the concentration of muscle
      glycogen, the high-energy phosphates (ATP and PCr), or metabolites (Pi, Cr, and
      lactate). Ex+Norm CHO also failed to modify the exercise-induced changes in CHO
      and fat oxidation. We conclude that prolonged exercise to fatigue performed 4
      days following glycogen-depleting exercise while on a normal CHO diet elevates
      resting Ca2+ uptake and prevents increases in SR membrane permeability to Ca2+ as
      measured by the ionophore ratio.

PMID- 16091791
TI  - Chemistry of aluminium(I).
AB  - In this article, we discuss the synthesis of tetrameric and monomeric
      aluminium(I) compounds. These compounds are prepared by reduction of the
      respective Al-X (X = halide) bond containing precursor. The tetrameric
      aluminium(I) compounds are synthesized by using sterically bulky ligands whereas
      a stable monomeric aluminium(I) compound is obtained using a monovalent chelating
      ligand. Theoretical studies are carried out on the monomer to understand the
      Lewis basicity. The presence of a lone pair of electrons plays an important role
      in the preparation of aluminium containing heterocyclic compounds, main group
      main group and transition metal-main group compounds having donor-acceptor bonds
      by carrying out reactions with unsaturated compounds and Lewis acids.

PMID- 16091792
TI  - In situ formation of ligand and catalyst--application in ruthenium-catalyzed
      enantioselective reduction of ketones.
AB  - The direct in situ formation of highly efficient ruthenium-catalysts for the
      asymmetric reduction of ketones was obtained by combining chiral ligand building
      blocks with a ruthenium precursor.

PMID- 16091793
TI  - Gold supported on a mesoporous CeO2 matrix as an efficient catalyst in the
      selective aerobic oxidation of aldehydes in the liquid phase.
AB  - Gold supported on CeO2 catalyses the selective aerobic oxidation of aliphatic and
      aromatic aldehydes better than other reported catalysts such as Pt/C/Bi
      materials; the activity is due to the nanometric particle size of Au and CeO2.

PMID- 16091794
TI  - Facile synthetic approach to novel core-extended perylene carboximide dyes.
AB  - The straightforward synthesis of two new classes of core-extended perylene
      chromophores, dibenzocoronene tetracarboxdiimide and indenoperylene
      dicarboxmonoimide, proves that directional enlargement of the aromatic pi-system
      leads to tailored bathochromic and hypsochromic shifts.

PMID- 16091796
TI  - Mixed monolayer coverage on gold nanoparticles for interfacial stabilization of
      immiscible fluids.
AB  - Gold nanoparticles covered with a mixed monolayer of n-dodecanethiol and 11
      mercapto-1-undecanol were prepared and found to mediate the oil-water interface,
      providing access to stable water droplets in oil.

PMID- 16091795
TI  - A two-dimensional clathrate hydrate sandwiched by planar arrays of a copper
      complex.
AB  - The first structurally characterised example of a 2-D clathrate hydrate
      spontaneously assembles when [CuF(tptm)] (tptm = tris(2-pyridylthio)methyl)
      crystallises from toluene/water solutions to produce a material in which planar
      arrays of [CuF(tptm)] sandwich and hydrogen bond to continuous 2-D sheets of
      water that incorporate toluene molecules at regular intervals.

PMID- 16091797
TI  - Enclathration of morpholinium cations by Dianin's compound: salt formation by
      partial host-to-guest proton transfer.
AB  - In spite of partial deprotonation upon inclusion of morpholine, Dianin's compound
      maintains its well-known clathrate structure in the solid state.

PMID- 16091798
TI  - A latent photoreaction predominates within water-soluble calixarenes:
      photochemistry of benzoin alkyl ethers.
AB  - Benzoin alkyl ethers encapsulated in a cisoid conformation within water-soluble p
      sulfonatocalix[8]arenes preferentially yield the Norrish Type II reaction product
      deoxybenzoin.

PMID- 16091799
TI  - First snapshot of a nonpolymeric hydrogelator interacting with its gelling
      solvents.
AB  - A pyridyl urea based low molecular weight supramolecular hydrogelator has been
      synthesized; crystallized from its gelling solvents, the single crystal structure
      of the gelator molecule interacting with its gelling solvents reported herein is
      the first example in the literature.

PMID- 16091800
TI  - Total synthesis of buergerinin F via effective construction of the asymmetric
      quaternary carbons using an enantioselective aldol reaction.
AB  - An efficient method for the synthesis of (+)-buergerinin F is established via the
      enantioselective aldol reaction of a tetra-substituted ketene silyl acetal with
      crotonaldehyde, followed by intramolecular Wacker-type ketalization.

PMID- 16091801
TI  - Networked calix[4]arene polymers with unusual mechanical properties.
AB  - Polymeric networks built from calix[4]arenes that form a three dimensional folded
      structure have been predicted to exhibit negative Poisson's ratios (auxetic), an
      unusual property which makes them superior to conventional materials in many
      practical applications.

PMID- 16091802
TI  - Directional control of pi-stacked building blocks for crystal engineering: the
      1,8-naphthalimide synthon.
AB  - Incorporating the 1,8-naphthalimide group into bis(pyrazolyl)methane ligands
      triggers the association of their rhenium(i) complexes into directionally ordered
      dimers in both solution and solid state, as demonstrated by ES+/MS, PGSE-NMR and
      X-ray diffraction studies.

PMID- 16091803
TI  - An organometallic chimie douce approach to new Re(x)W(1-x)O3 phases.
AB  - Re(x)W(1-x)O3.H2O and Re(x)W(1-x)O3 phases are prepared by a new organometallic
      chimie douce concept employing the organometallic precursor methyltrioxorhenium.

PMID- 16091804
TI  - Demethylation of the [Me3Sn(PhN2O2)]4 tetramer into dimeric [Me2Sn(PhN2O2)2]2: a
      thermally induced methyl-transfer between supramolecules.
AB  - The single crystals of tetrameric [Me3Sn(PhN2O2)]4 (1) supramolecule demethylates
      into single crystals of [Me2Sn(PhN2O2)2]2 dimer (2) and volatile Me4Sn, as a
      result of a crystal-to-crystal supramolecular structural transformation, which
      occurs upon heating and it is accompanied by a significant change of the
      molecular and crystal structures.

PMID- 16091805
TI  - Enantiomerically pure P-chiral phosphinoselenoic chlorides: inversion of
      configuration at the P-chirogenic center in the synthesis and reaction of these
      substances.
AB  - Reaction of diastereomerically pure phosphinoselenoic acid salts with oxalyl
      chloride leads to enantiomerically pure P-chiral phosphinoselenoic chlorides with
      inversion of configuration at phosphorus; one of these chlorides is converted to
      a phosphinoselenothioic acid salt with a high degree of enantioselectivity.

PMID- 16091806
TI  - Precise synthesis of poly(macromonomer)s containing sugars by repetitive ring
      opening metathesis polymerisation.
AB  - Various poly(macromonomer)s containing sugars have been prepared by ROMP of
      norbornene macromonomers substituted with ROMP block copolymers containing acetal
      protected sugars as the side chain, which upon removal of the protecting group
      affords a novel amphiphilic architecture.

PMID- 16091807
TI  - CdTe@Co(OH)2 (core-shell) nanoparticles: aqueous synthesis and characterization.
AB  - A seed-mediated growth approach for preparation of multifunctional CdTe@Co(OH)2
      (core-shell) nanoparticles in the aqueous phase is reported.

PMID- 16091808
TI  - Ru(IV)-catalyzed isomerization of allylamines in water: a highly efficient
      procedure for the deprotection of N-allylic amines.
AB  - A general and efficient method for the deprotection of N-allylic substrates in
      aqueous media, using catalytic amounts of the bis(allyl)-ruthenium(IV) complexes
      [Ru(eta3:eta2:eta3-C12H18)Cl2] and [{Ru(eta3:eta3-C10H16)(micro-Cl)Cl}2], has
      been developed.

PMID- 16091809
TI  - Hydrophobic magnetic nanoparticles induce selective bioelectrocatalysis.
AB  - Hydrophobic magnetic nanoparticles were used to sense selectively lactate and
      glucose at the same applied potential.

PMID- 16091810
TI  - Redox behaviour of Pd-based TWCs under dynamic conditions: analysis using
      dispersive XAS and mass spectrometry.
AB  - The redox behaviour of Pd-based TWCs is studied under dynamic, cycling conditions
      (e.g. lambda oscillations) on a 50 millisecond scale. Pd temporal response to gas
      inlet mixture changes is governed by metal-promoter interface properties.

PMID- 16091811
TI  - Chemical instability of octadecylammonium monolayers.
AB  - Octadecylammonium in monolayers transforms into a carbamate derivative, as
      observed by attenuated total reflection Fourier transform infrared (ATR-FTIR)
      spectroscopy and 13C nuclear magnetic resonance (NMR) spectroscopy.

PMID- 16091812
TI  - Organic dyes containing thienylfluorene conjugation for solar cells.
AB  - New organic dyes that contain variable lengths of conjugation featuring
      alternating thiophene and fluorene segments have been synthesized and efficient
      nano-crystalline TiO2 based dye-sensitized solar cells were fabricated using
      these molecules as light-harvesting sensitizers.

PMID- 16091813
TI  - Cobalt oxide hollow nanoparticles derived by bio-templating.
AB  - We present here the first fabrication of hollow cobalt oxide nanoparticles
      produced by a protein-regulated site-specific reconstitution process in aqueous
      solution and describe the metal growth mechanism in the ferritin interior.

PMID- 16091814
TI  - A unique microwave effect on the microstructural modification of Cu/ZnO/Al2O3
      catalysts for steam reforming of methanol.
AB  - A short time (3-10 min) of microwave irradiation on the CuO/ZnO/Al2O3 oxide
      precursor can result in a unique tailored microstructural modification on the
      catalyst, leading to a significantly enhanced performance for H2 production from
      steam reforming of methanol.

PMID- 16091815
TI  - Colloidal lithography with crosslinkable particles: fabrication of hierarchical
      nanopore arrays.
AB  - We demonstrate that colloidal lithography with self-assembled monolayers of
      crosslinkable polymeric particles can be used to create hierarchical arrays of
      nanopores on substrates.

PMID- 16091816
TI  - Au nanoparticle-imprinted polymers.
AB  - Au nanoparticles protected with a polymerisable ligand were incorporated into
      bulk macroporous polymers; etching the metal core resulted in disulfide-lined,
      nanometre-scale cavities capable of recognising similarly-sized Au particles.

PMID- 16091817
TI  - Photosensitizing properties of 2,4-dichlorobenzoic acid and chlorinated biphenyl
      carboxylic acids, potentially key components of chromophoric dissolved organic
      matter.
AB  - 2,4-Dichlorobenzoic acid and a suite of models of chlorinated biphenyl carboxylic
      acids were found to be efficient sensitizers of the reactive oxygen species
      singlet oxygen (1O2).

PMID- 16091818
TI  - Chiral azide-bridged two-dimensional Cu(II) compounds showing a field-induced
      spin-flop transition.
AB  - Two azide-bridged chiral Cu(II) compounds, [Cu(R,R-dacy)(N3)2]n (R,R-dacy = trans
      (1R,2R)-diaminocyclohexane) and [Cu(S,S-dacy)(N3)2]n (S,S-dacy = trans-(1S,2S)
      diaminocyclohexane), with two-dimensional layer structures exhibiting end-to-end
      and end-on azide bridging patterns, were prepared and among them was examined to
      show a field-induced spin-flop transition.

PMID- 16091819
TI  - Efficient two-step synthesis of 3-halo-3-enals or 2-halo-2-alkenyl ketones from
      propargylic bromides via a unique cationic 1,2-aryl or proton shift in
      electrophilic addition reaction of 2,3-allenols with X+.
AB  - The reaction of readily available 1-substituted 2,3-allenols with Br2, NBS, or I2
      afforded the not-easily-available but synthetically useful 3-halo-3-alkenals or 2
      halo-2-alkenyl ketones in good yields via a sequential electrophilic interaction
      of X+ with the allene moiety , a 1,2-aryl or proton shift, and a H+-elimination
      process; the structures of the products were established by X-ray diffraction
      study.

PMID- 16091820
TI  - Size dependent interaction of biofunctionalized CdS nanoparticles with tyrosine
      at different pH.
AB  - Enhancement of fluorescence of CdS nanoparticles by tyrosine at pH 10 in contrast
      to Stern-Volmer quenching at pH 7 was observed and both the effects were found to
      depend on the size of the nanoparticles.

PMID- 16091821
TI  - Post-traumatic anterior and posterior pituitary dysfunction.
AB  - BACKGROUND AND PURPOSE: The recognition of hypopituitarism after head trauma is
      important because related neurobehavioral problems can be alleviated by hormone
      replacement. This study investigated the clinical presentations and imaging
      findings of patients with hypopituitarism developing after head trauma. METHODS:
      We retrospectively reviewed the medical records of patients with hypopituitarism
      from 1982 through 2002. Data on disease history and hormone deficiencies of
      patients with hypopituitarism which developed after head trauma were analyzed.
      RESULTS: Eighteen patients with hypopituitarism or diabetes insipidus (DI) due to
      head trauma, including 11 men and 7 women, were identified. Head trauma thus
      accounted for the etiology in 2.8% of all 635 patients with a diagnosis of
      hypopituitarism during the study period. The major cause of head trauma was road
      accident (n = 11, 61%). Ten of the patients (56%) had lost consciousness after
      the head injury. The duration from head trauma to the onset of symptoms of
      hypopituitarism ranged from < 1 month to 15 years. Sex hormone (61%) and growth
      hormone (56%) were the most common hormone deficiencies, followed by
      corticotropin deficiency (39%) and thyrotropin deficiency (22.2%). DI developed
      in 9 patients (50%) and 5 of these patients had only DI without anterior
      hypopituitarism. Routine skull radiograph did not show abnormal signs. Among the
      10 patients with magnetic resonance imaging of the pituitary gland, a small or
      atrophic anterior lobe was seen in patients with anterior hypopituitarism. Loss
      of bright signal intensity from the pituitary posterior lobe on T1-weighted
      magnetic resonance imaging was seen in all 3 patients with DI. An ectopic
      posterior lobe could be seen in 2 patients with hypopituitarism without DI.
      CONCLUSIONS: Identification of head trauma as the etiology of hypopituitarism may
      be overlooked if there is a long delay in onset after trauma. DI is a common
      early complication. Since anterior hypopituitarism can develop decades after the
      episode of head trauma, monitoring for endocrine dysfunction during follow-up of
      these patients is important.

PMID- 16091822
TI  - Effectiveness of coping strategies used by hospitals in response to
      implementation of a case-based payment system by the National Health Insurance
      program.
AB  - BACKGROUND AND PURPOSE: The introduction of the case-based payment system by the
      Bureau of National Health Insurance resulted in greatly increased pressure on the
      health care industry in Taiwan. This study examined the relationship between the
      coping strategies adopted and the results attained by accredited teaching
      hospitals and non-teaching regional hospitals when responding to this regulatory
      change. METHODS: A cross-sectional survey was conducted using a structured
      questionnaire to assess the hospitals' characteristics, and coping strategies at
      the technical, managerial and institutional levels in response to the case-based
      payment system, and to compare these strategies with self-evaluation of the
      effectiveness of these strategies. The questionnaire was sent in early October
      2000 to the superintendents of the 129 hospitals that were accredited at the
      medical center, regional hospital, and district teaching hospital levels in the
      year 2000. Factor analysis was applied to group the strategies into categories
      and stepwise regression analysis was used to explore the relationship between the
      reported coping strategies adopted and their effectiveness as evaluated by
      participants. RESULTS: Among the selected hospitals, 89 responded with complete
      data, a 69% response rate. The following 7 factors were extracted from 30 coping
      strategies: information and financial analysis; service shifting and unbundling;
      service integration and quality improvement; service specialization and
      strengthening; education and training; financial incentives; and claim submission
      skill. After adjusting for accreditation level or ownership status, 2 main
      findings were noted. First, hospitals that implemented financial incentives
      strategies such as holding physicians responsible for all or part of the
      shortfall between actual claim submissions and actual reimbursements, and
      reducing or withholding payment to physicians beyond the standard length of stay,
      tended to increase medical revenue (odds ratio, 1.21). Second, hospitals that
      implemented service integration and quality improvement strategies, such as
      implementing a discharge plan, implementing clinical pathways and periodic review
      of quality indicators, attained higher patient satisfaction rate (odds ratio,
      1.40). CONCLUSIONS: This study suggests that hospitals confronting the
      implementation of a case based-payment system may benefit by adopting financial
      incentives strategies and by efforts to improve service integration and quality.

PMID- 16091824
TI  - Renal dysfunction after heart transplantation: incidence, prognosis and risk
      factors.
AB  - BACKGROUND AND PURPOSE: Despite more than 20 years of experience in heart
      transplantation, the risk factors for development of chronic renal insufficiency
      in recipients are not well established. This study assessed the incidence,
      prognosis and risk factors for renal dysfunction after heart transplantation.
      METHODS: We conducted a retrospective analysis of all adult patients (n = 132)
      who survived for more than 1 year after heart transplantation at our institutions
      from March 1992 through November 2002. Renal dysfunction was defined as serum
      creatinine of > or = 2.0 mg/dL. The incidence and prognosis of renal dysfunction
      after heart transplantation was estimated by the Kaplan-Meier method and compared
      by log rank test. Risk factors for renal dysfunction at 1 year after
      transplantation were evaluated using a logistic regression model. RESULTS: Renal
      dysfunction was present in 9 patients (7%) before heart transplantation. The
      cumulative incidence of renal dysfunction after heart transplantation was 23.0 +/
      3.8%, 36.1 +/- 4.3%, 53.9 +/- 4.9%, and 57.3 +/- 5.8% at 6 months, 1 year, 5
      years and 10 years, respectively, after transplantation. The actuarial survival
      rate in patients without renal dysfunction at 1 year after transplantation was
      better than for patients with renal dysfunction at 1 year after transplantation
      (p = 0.046 by log-rank test). Independent risk factors for renal dysfunction at 1
      year after transplantation were age at transplantation (odds ratio, 1.07; p =
      0.02), pretransplant serum blood urea nitrogen (odds ratio, 1.07; p = 0.048), and
      serum creatinine at 6 months after transplantation (odds ratio, 17.0; p < 0.001).
      CONCLUSIONS: There was a high incidence of renal dysfunction after heart
      transplantation. Patients with renal dysfunction had poor long-term prognosis.
      Serum creatinine at 6 months after transplantation was the most significant major
      risk factor, followed by age at transplantation and pretransplant blood urea
      nitrogen.

PMID- 16091823
TI  - Machine and operator performance analysis of automated external defibrillator
      utilization.
AB  - BACKGROUND AND PURPOSE: The availability of an automated external defibrillator
      (AED) can improve the outcome of patients with out-of-hospital cardiac arrest
      (OHCA). On June 1, 2000, Taipei City became the first city in Taiwan to equip
      emergency medical services personnel with AEDs. This study was conducted to
      assess the performance of the AED machine in detecting ventricular fibrillation
      (VF) and ventricular tachycardia (VT) in the population, and to assess operator
      performance in its use. METHODS: AED use in OHCA patients was assessed over a 1
      year period. Electrocardiography and voice records retrieved from AED data cards
      were analyzed. A shockable rhythm was defined as either VF or VT. AED machine
      performance was assessed based on the correct identification of these rhythms.
      Operator performance was evaluated according to American Heart Association
      guidelines. RESULTS: A total of 978 AED rhythm analyses were obtained for 653
      OHCA patients. The sensitivity and specificity for detecting shockable rhythms by
      the AED machine were 90.0% (95% confidence interval [CI], 85.3% to 93.3%) and
      100% (95% CI, 99.5% to 100%), respectively. Sensitivity for coarse VF, fine VF,
      rapid VT, and slow VT was 97.5%, 74.2%, 63.6% and 60.0%, respectively. An AED was
      deployed in 18 non-OHCA patients and in 119 patients after they had been moved
      into the ambulance. Non-compliance with standard procedures occurred during AED
      use in 162 patients, including interference of movement by cardiopulmonary
      resuscitation (CPR) in progress in 69, untimely machine turn-off in 49, leads
      fell off or disconnected in 33, failure of shock delivery after charge in 28, and
      interference of movement other than CPR in 22. CONCLUSIONS: This study found that
      the AED machine has high specificity and high sensitivity in detecting VF and VT,
      especially coarse VF. Efforts are needed to improve the timing of AED deployment
      and emergency medical technician compliance with standard procedures.

PMID- 16091825
TI  - Ross procedure for pediatric aortic valve disease.
AB  - BACKGROUND AND PURPOSE: Currently, prosthetic selection for aortic valve
      replacement is still debatable in pediatric patients with aortic valve disease.
      Ross procedure is a time-consuming and demanding technique which may produce good
      results. This study assessed the results obtained with various methods of right
      ventricle outflow tract (RVOT) reconstruction in patients receiving Ross
      procedure. METHODS: From September 1996 to December 2003, 13 pediatric patients
      underwent Ross procedure for aortic valve disease. Their ages ranged from 1 month
      to 17 years (mean, 6.29 +/- 3.62 years; median, 7 years) and 2 patients were less
      than 1 year of age. Previous procedures in these patients included balloon
      dilation of the aortic valve in 10 and surgical aortic valvuloplasty in 2. RVOT
      was reconstructed with heterografts in 3, homografts in 3 or without extracardiac
      conduits in 7. RESULTS: There was 1 in-hospital death (7.7%) and 1 late death
      from a non-cardiac cause. One patient developed infective endocarditis with
      periaortic abscess 2 weeks after the Ross procedure. Eleven patients were
      followed for a mean of 3.3 years (range, 8 months to 8 years). There was no
      significant pressure gradient across the neoaorta. Severe stenosis developed
      gradually in 3 patients who had RVOT reconstruction with heterograft conduits.
      All 3 had received RVOT redo operation. None of the patients who received RVOT
      reconstruction without extracardiac conduits had significant pulmonary stenosis
      but 6 had regurgitation (nil 1, mild 3, moderate 3). No redo operation was
      required during follow-up (range, 8 months to 4 years). All of the 11 survivors
      were in New York Heart Association functional class I. CONCLUSIONS: This study
      found satisfactory results of Ross procedure in pediatric aortic valve disease.
      RVOT reconstruction without extracardiac conduit is a feasible alternative
      despite the availability of homograft.

PMID- 16091826
TI  - Starting position and stretching velocity effects on the reflex threshold angle
      of stretch reflex in the soleus muscle of normal and spastic subjects.
AB  - BACKGROUND AND PURPOSE: Although both starting position and stretching velocity
      play an important role in reflex response, their interaction with stretch
      reflexes has not been thoroughly investigated. This study examined the
      interaction effect of starting position and stretching velocity on the reflex
      threshold angle (RTA) of the stretch reflex in the soleus muscle of normal and
      spastic subjects. METHODS: The spastic group included 11 ankles from 7 subjects
      with a history of upper motor neuron lesions. Their ages ranged from 22 to 40
      years. Another 10 healthy subjects served as the control group. RTAs of the
      stretch reflex in the soleus muscle were measured for a matrix of starting
      positions and stretching velocities. The matrix design enabled the use of a 2-way
      analysis model to investigate the effect of starting position and stretching
      velocity on the RTA. RESULTS: No interaction effect was found in either the
      phasic stretch reflex (PSR) or the tonic stretch reflex (TSR) in the spastic
      group, or in the PSR in the normal group. The RTA of the PSR in both spastic and
      normal groups was significantly affected by starting position but not by
      stretching velocity. In contrast, the RTA of the TSR in the spastic group was
      affected by both starting position and stretching velocity. Stretching velocity
      and starting position played independent roles in determining the RTA of both the
      PSR and the TSR of the spastic group and in the PSR of the normal group.
      CONCLUSIONS: The lack of interaction between length-sensitive and velocity
      sensitive muscle spindles in both normal and spastic subjects supports the
      hypothesis that they independently modulate the stretch reflex. Results for the
      RTA of the TSR demonstrated that spasticity results in disinhibition of
      motoneuron excitability with different thresholds.

PMID- 16091827
TI  - Quality of sputum smear microscopy in Taiwan.
AB  - BACKGROUND AND PURPOSE: Four mycobacteriology laboratories in northern Taiwan
      collected slides from their routine work for an international training course on
      quality assurance of sputum smear microscopy held from 19-27 August 2004 in
      Taipei. Rechecking of a random sample of these slides provided an opportunity to
      evaluate the quality of sputum smear microscopy in the collaborating
      laboratories. METHODS: Participants used a systematic sampling method to choose
      100 to 120 slides from a set of 600 to 800 slides for evaluating the quality of
      smear and rechecking. Recheckers were blinded to the microscopy results reported
      by the testing laboratories. Discordant slides were re-examined by a second
      rechecker in order to make the final decision. RESULTS: A total of 433 slides
      were evaluated for smear quality. Of these 433 slides, 177 (41%) had proper smear
      size, 194 (45%) proper thickness and 212 (49%) proper staining. Rechecking of
      slides revealed that 2 of 4 laboratories had at least 1 high false-negative and 3
      of 4 laboratories had at least 1 low false-negative result. CONCLUSIONS: We
      conclude that: 1) the 2 laboratories with high false-negative results need a
      supervisory visit in order to determine the causes; and 2) the national
      tuberculosis program should direct more attention to the quality of sputum smear
      microscopy and develop a formal plan for external quality assessment of sputum
      smear microscopy in Taiwan.

PMID- 16091828
TI  - Successful treatment of acute hepatitis A-associated hemophagocytic syndrome by
      intravenous immunoglobulin.
AB  - Virus-associated hemophagocytic syndrome (VAHS) is a rare complication in acute
      hepatitis A virus (HAV) infection. There is no standard therapy for VAHS and the
      clinical course is variable. Data on the use of intravenous immunoglobulin (IVIG)
      in the treatment of HAV-associated VAHS is limited. We report a previously
      healthy, 32-year-old man who presented with general malaise, fever, chills and
      splenomegaly. Laboratory examination showed marked elevation of aminotransferase,
      leukopenia and thrombocytopenia. Acute hepatitis A was documented by the presence
      of immunoglobulin M anti-HAV and compatible liver biopsy findings. Bone marrow
      examination revealed extensive hemophagocytosis. IVIG was administered after the
      diagnosis of HAV-associated VAHS. His symptoms and laboratory abnormalities
      improved, and following a smooth recovery he was discharged 1 month after
      admission.

PMID- 16091829
TI  - Blood-aqueous barrier function in a patient with combined hamartomas of the
      retina and retinal pigment epithelium.
AB  - Clinical data showing breakdown in the blood-aqueous barrier in patients with
      combined hamartomas of the retina and retinal pigment epithelium are very
      limited. We used a laser flare-cell meter to examine blood-aqueous barrier
      function in a 35-year-old male patient who had typical combined hamartomas of the
      retina and retinal pigment epithelium characterized by an ill-defined, slightly
      elevated, grey-white epipapillary lesion with overlying glial proliferation and
      surrounding vascular tortuosity. Fluorescein angiography showed early
      hypofluorescence corresponding to the pigmented area with speckled
      hyperfluorescence in the lesion. Prominent retinal vascular tortuosity and late
      dye leakage were noted in the late phase. Visual evoked potential demonstrated
      poor waveform. Laser photometry showed an increase in the aqueous flare intensity
      in the affected eye, as compared to the results in the unaffected eye and to data
      from normal subjects. The increase in the aqueous flare intensity in this patient
      suggests that the function of the blood-aqueous barrier may be affected in
      combined hamartomas of the retina and retinal pigment epithelium.

PMID- 16091830
TI  - Computed tomography diagnosis of primary thyroid teratoma.
AB  - Teratomas occur mainly in the gonads, and rarely in the thyroid. They are common
      in reproductive age women. Teratomas in the thyroid occur mainly in neonates and
      are often benign. Here we report a case of primary benign teratoma of the thyroid
      gland in a 15-year-old female, which was accurately diagnosed by computed
      tomography before surgery. The tumor was a well-defined cystic mass in the right
      thyroid region, with a fat-containing nodule in the cystic tumor causing
      displacement of the trachea. The patient was treated with right subtotal
      thyroidectomy and no recurrence was noted during 2 years' follow-up.
      Demonstration of the fat component within a well-defined cystic mass in the
      thyroid region allows accurate diagnosis of teratoma, localization of the tumor
      extent before operation, and adequate treatment.

PMID- 16091831
TI  - Recurrent panniculitis associated with generalized lipodystrophy and growth
      hormone deficiency.
AB  - Generalized lipodystrophy (GLD) is characterized clinically by an almost complete
      lack of fat in adipose tissue. Traditionally, GLD can be divided into congenital
      and acquired types according to the clinical course and underlying etiologies.
      Here, we describe a boy with a probable diagnosis of acquired GLD. He showed
      recurrent panniculitis since early infancy, and short stature with delayed
      skeletal age (3 years less) and low levels of insulin-like growth factor-1 (IGF
      1) and IGF binding protein-3. Growth hormone (GH) deficiency was confirmed by GH
      provocative tests (peak GH below 5 microg/L). In addition to slow progressive
      loss of subcutaneous fat tissue, he also suffered from hepatosplenomegaly,
      recurrent febrile episodes in association with painful nodular skin lesions and
      abdominal pain. The diagnosis of lipodystrophic panniculitis was confirmed after
      skin biopsy. The febrile episodes and skin lesions responded to oral
      corticosteroid with the progression of time. Acquired GLD with GH deficiency
      (e.g., recurrent panniculitis) may occur as a result of chronic inflammation over
      the pituitary stalk and pituitary gland. The use of steroid and GH replacement
      may alleviate this disorder.

PMID- 16091832
TI  - Balloon valvuloplasty for critical aortic stenosis in a low birth weight baby
      with tracheoesophageal fistula.
AB  - The use of valvuloplasty in low birth weight infants with valvular aortic
      stenosis has not been widely reported. We report a 1556 g 3-day-old female infant
      with complex heart disease including critical valvular aortic stenosis, bicuspid
      aortic valve, mitral stenosis, patent ductus arteriosus, and secundum type atrial
      septal defect. She also had esophageal atresia with a distal tracheoesophageal
      fistula and trisomy 18. Balloon valvuloplasty was considered to be more dangerous
      in this patient than in infants with simple critical aortic stenosis without
      other associated anomalies or low birth weight. Retrograde aortic balloon
      valvuloplasty was done carefully with the patient intubated and mechanically
      ventilated. We successfully dilated the stenotic aortic valve, which resulted in
      a dramatic decrease of the left ventricular pressure from 139/12 mm Hg to 81/11
      mm Hg. Despite the high operative risk and poor prognosis, balloon valvuloplasty
      may be the first feasible step towards the survival of low birth weight infants
      with valvular aortic stenosis.

PMID- 16091833
TI  - Six cases of deletion 9p24 and trisomy 19q13.4 inherited from a familial balanced
      translocation.
AB  - The deletion 9p with trisomy 19q syndrome is a rare disorder. We report 2 adults
      and 4 children with deletion 9p and trisomy 19q due to familial balanced 9p;19q
      translocation with clinical features suggestive of monosomy 9p. The children had
      dysmorphic features and psychomotor retardation while the adults were self
      sufficient but worked in a sheltered environment. High-resolution chromosome
      analysis and fluorescence in situ hybridization confirmed that the 6 cases of
      unbalanced translocation, der(9)t(9;19)(p24.1;q13.4) were inherited from a
      balanced translocation carrier, t(9;19)(p24.1;q13.4). The dysmorphic features
      included trigonocephaly, small nose with stunted tip, and long philtrum.
      Associated anomalies included wide-set nipples, extra finger flexion creases,
      hernia, external genitalia hypoplasia, scoliosis, and hypopigmented skin patch.
      We suggest that genetic counseling is necessary for those who have family members
      with dysmorphic features and/or major anomalies and/or psychomotor retardation.

PMID- 16091834
TI  - Frequent occurrence of protein isoforms with or without a single amino acid
      residue by subtle alternative splicing: the case of Gln in DRPLA affects
      subcellular localization of the products.
AB  - Protein isoforms with or without a single amino acid residue make a subtle
      difference. It has been documented on a few genes that alternative splicing
      generated such isoforms; however, the fact has attracted little attention. We
      became aware of a subtle sequence difference in DRPLA, a polyglutamine disease
      gene for dentatorubral pallidoluysian atrophy. Some reported cDNA sequences
      lacked 3 nucleotides (nt) (CAG), which were positioned apart from the expandable
      and polymorphic CAG repeats and also coded for glutamine. We experimentally
      confirmed that the difference was indeed generated by alternative splicing
      utilizing two acceptors separated by 3 nt. In DRPLA, the expression ratio of two
      mRNA isoforms was almost constant among tissues, with the CAG-included form being
      major. The glutamine-included protein isoform was more predominantly localized in
      the nucleus. Database searching revealed that alternative splice acceptors, as
      well as donors, are frequently situated very close to each other. We
      experimentally confirmed two mRNA isoforms of 3 nt difference in more than 200
      cases by RT-PCR and found interesting features associated with this phenomena.
      Inclusion of 3 nt tends to result in single amino acid inclusion despite the
      phase of translational frame. The expression ratio sometimes varied extensively
      among tissues.

PMID- 16091835
TI  - Recommendations for an update of the current (2001) regulatory requirements for
      registration of drugs to be used in the treatment of osteoporosis in
      postmenopausal women and in men.
AB  - Recent advances in the understanding of the epidemiology of osteoporosis suggest
      that certain parts of the current European guidelines for the registration of
      drugs in osteoporosis might be no longer substantiated. The object of this review
      is to provide the European regulatory authorities with an evidence-based working
      document providing suggestions for the revision of the "Note for guidance for the
      approval of drugs to be used in postmenopausal osteoporosis" (CPMP/EWP/552/95).
      Following an extensive review of the literature (1990-2004), the Group for the
      Respect of Ethics and Excellence in Science (GREES) organized a workshop
      including European regulators, academic scientists and representatives of the
      pharmaceutical industry. The outcomes of this meeting reflect the personal views
      of those who attended and should not, in any case, be seen as an official
      position paper of any regulatory agency. The group identified a certain number of
      points that deserve discussion. They mainly relate to the nature of the
      indication being granted to new chemical entities (treatment of osteoporosis in
      women at high risk of fracture instead of prevention and treatment of
      osteoporosis), the requirements of showing an anti-fracture efficacy on all or on
      major nonvertebral fractures (instead of the hip), the duration of pivotal trials
      (2 years instead of 3) and the possibility of considering bridging studies for
      new routes of administration, new doses or new regimens of previously approved
      drugs. The group also recommends that an indication could be granted for the
      treatment of osteoporosis in males on the basis of a placebo-controlled study,
      with bone mineral density changes after 1 year as the primary endpoint, for
      medications approved in the treatment of osteoporosis in women at high risk of
      fractures.

PMID- 16091836
TI  - Determinants of incidence of osteoporotic fractures in the female Spanish
      population older than 50.
AB  - It is well known that the adoption of preventive measures for osteoporosis may
      contribute to minimizing its impact as a result of bone fractures. However, there
      are well-recognized risk factors involved in the onset of osteoporosis that are
      not possible to modify. Better knowledge of these non-modifiable factors could
      aid prevention in subjects at high risk of fractures. The aim of this study was
      to evaluate the likely association between gynecological, reproductive and family
      history of hip fracture with the incidence of vertebral and nonvertebral
      osteoporotic fractures in women older than 50. We studied 255 women aged 50 and
      over, randomly selected from a Spanish population that had participated in a
      study of prevalence of vertebral fractures (EVOS study). This cohort was
      prospectively followed for 8 years by means of four postal questionnaires, in
      order to find out the incidence of nonvertebral fractures. Concerning the
      incidence of vertebral fractures, participants were invited to repeat the lumbar
      spine X-rays 4 years after the initial study. A total of 31 women had incident
      osteoporotic fractures. The analysis of gynecological variables showed that an
      increase in the age at menarche was a risk factor for all incident osteoporotic
      fractures [OR=1.57 (1.04-2.37)]. The presence of amenorrhea at any age during the
      fertile period was associated with higher incidence of all osteoporotic fractures
      [OR=6.30 (1.61-24.70)]. Among all the reproductive variables analyzed (pregnancy,
      number of live births and breast-feeding) only pregnancy was an important
      protective factor in preventing incident Colles fracture [OR=0.15 (0.03-0.62)]. A
      family history of hip fracture was associated with a higher incidence of all
      osteoporotic fractures [OR=3.59 (1.01-12.79)]. In summary, a late age at
      menarche, the presence of amenorrhea and having close relatives with hip fracture
      were all risk factors which, independently of bone mineral density (BMD) and age,
      were associated with higher incidence of all osteoporotic fractures. Pregnancy
      was an important protective factor for the incidence of Colles fractures.

PMID- 16091837
TI  - High parity is associated with increased bone size and strength.
AB  - Some, but not all, studies report an association between decreased hip fracture
      risk and high parity despite similar bone mineral density (BMD). Our hypothesis
      was that bone size, a major determinant of bone strength, is greater in women
      with high parity compared with low parity or nulliparous women. A cross-sectional
      study of 168 Hutterite women aged 40-80 years was conducted. BMD, bone mineral
      content (BMC) and bone area of the total body (TB), hip, femoral neck (FN), and
      lumbar spine (LS) were measured, as well as bone geometry at the 4% and 20%
      distal radius and bending strength at 20% radius. Diet and activity recall and
      strength measurements were obtained. Of the 168 women, 42 (25%) were nulliparous
      while the remaining women reported 1 to 16 births (median=6). Of the 126 parous
      women, 122 (97%) breast-fed their infants (range 1.5-24 months). Hip, FN and LS
      BMD were not associated with either parity or months of breast-feeding. TB BMC
      and bone area (both, p<0.05) and FN bone area (p<0.01) were associated with
      parity. FN bone area was 4% greater in women with 7+ vs 1-4 children. Torsional
      bending strength, which includes structural and material bone properties, at the
      20% distal radius was greater with higher parity (p=0.01). No bone measure was
      associated with average months of breast-feeding. High parity is associated with
      increased radial torsional bending strength and femoral neck size. The greater
      femoral neck size, without higher BMD, may explain the reduced hip fracture risk
      among women with high parity previously reported in some studies.

PMID- 16091838
TI  - Pulmonary involvement in lifelong non-smoking patients with rheumatoid arthritis
      and ankylosing spondylitis without respiratory symptoms.
AB  - Pulmonary involvement seen in rheumatoid arthritis (RA) and ankylosing
      spondylitis (AS) has been detected increasingly by using highly sensitive
      diagnostic techniques such as high-resolution computed tomography (HRCT).
      However, HRCT findings in healthy controls and the effects of smoking and drugs
      have not been well studied. The aim of this controlled study was to evaluate the
      relationships between disease-specific clinical, laboratory, HRCT and pulmonary
      function test (PFT) findings in 20 RA patients using methotrexate (MTX) and 20 AS
      patients using sulphasalazine who were non-smokers and exhibited asymptomatic
      respiratory signs. For this purpose, a total of 60 persons (40 patients and 20
      healthy controls) were included in this study. A restrictive pattern on PFT was
      detected in four patients (20%) with AS, one patient with RA and one control
      (p<0.05). Fourteen patients (70%) with RA and ten patients (50%) with AS had
      positive HRCT findings. Only one patient (5%) in the control group had abnormal
      HRCT findings (p<0.05). Interstitial lung disease (ILD) was the most frequently
      seen HRCT finding in both the RA (35%) and AS (20%) groups. The chest expansion
      measurement, the score of the visual analogue scale (VAS) for pain and C-reactive
      protein (CRP) levels were statistically significantly better in patients with AS
      having normal HRCT than in those with abnormal findings (p<0.05). There was no
      correlation detected between HRCT and duration of disease, disease activity
      markers, functional indexes and PFT in patients with RA and AS. HRCT is a
      sensitive tool in detecting ILD in patients with RA and AS with no signs and
      symptoms of pulmonary involvement and may be an integral part of such work-up.
      However, future prospective studies are needed to better determine if HRCT is in
      fact a predictor of subsequent MTX toxicity.

PMID- 16091839
TI  - Clinical significance of IgA anticardiolipin and anti-beta2-GP1 antibodies in
      patients with systemic lupus erythematosus and primary antiphospholipid syndrome.
AB  - The objectives of this study were to estimate the prevalence of IgA
      anticardiolipin antibodies (aCL) and anti-beta(2)-glycoprotein 1 antibodies
      (abeta(2)-GP1) in a large number of patients with systemic lupus erythematosus
      (SLE) and primary antiphospholipid syndrome (PAPS) and to examine possible
      associations between the clinical manifestations of the APS and the levels of IgA
      aCL and abeta(2)-GP1. We also assessed the operative characteristics of IgA aCL
      and abeta(2)-GP1. We retrospectively studied 130 patients with SLE and 35
      patients with PAPS. In all patients we measured IgG, IgM, and IgA aCL and
      abeta(2)-GP1 and recorded any of the clinical manifestations of the APS. IgA aCL
      were positive in 8.5% of patients with SLE and in 40% of patients with PAPS.
      Positive IgA abeta(2)-GP1 were found in 17.7% of patients with SLE and in 25.7%
      of patients with PAPS. IgA aCL were associated with a history of venous
      thrombosis, thrombocytopenia, and recurrent fetal loss. In contrast, we could not
      establish significant associations between IgA abeta(2)-GP1 and any of the
      clinical manifestations of the APS. Measurement of the IgA in addition to IgG and
      IgM aCL hardly changed the operative characteristics of aCL testing, while
      measurement of the IgA in addition to IgG and IgM abeta(2)-GP1 increased
      sensitivity but with a greater loss in specificity. IgA aCL is significantly
      associated with more than one of the clinical manifestations of the APS in
      contrast to the IgA abeta(2)-GP1. Routine measurement of the IgA isotype of both
      aCL and abeta(2)-GP1 does not improve the operative characteristics of aCL and
      abeta(2)-GP1 and therefore is not recommended at present.

PMID- 16091840
TI  - Effect of ankylosing spondylitis on health-related quality of life and different
      aspects of social life in young patients.
AB  - The aim of this study was to determine the emotional and sociodemographic
      characteristics of patients with ankylosing spondylitis (AS) and to investigate
      the impact of the disease on their social life and quality of life (QOL). This
      study included 101 patients with the diagnosis of AS. All patients filled in a
      questionnaire comprising their sociodemographic and emotional status and their
      self-rating on the disease and completed the 36-item Short Form Health Survey (SF
      36). The impact of the disease on work status, sexuality, and family relations
      was measured on a Likert scale. The impact of the disease on employment, family
      and sexual relations, work life as well as SF-36 was investigated. Therefore, the
      effect of educational level, employment, social security, and sexual relations
      with spouse, etc. on QOL were assessed. More than half of the patients had no
      knowledge about the disease and half of them were not under a physician's
      control. Thirty-two percent of the previously working patients quit their jobs
      because of the disease. Quitting a job due to the disease was more frequent in
      the first 10 years of the disease. The most affected domains of the SF-36 were
      physical role power, general health, and pain. Patients unemployed due to the
      disease had lower SF-36 scores compared with employed ones. Unemployed patients
      without social insurance had lower values on SF-36 subscales (p<0.05). A higher
      education level had positive influences on disease impact. The level of anxiety
      was high and was associated with sexual relations (p<0.05). Our results show that
      the disease affects patients' work and social life. Work disability affects QOL.
      Educating the patients about the disease may play an important role in improving
      his/her life quality and coping with the disease. Thus, the socioeconomic burden
      of the disease on the person and on society can be diminished.

PMID- 16091841
TI  - Neridronate and human osteoblasts in normal, osteoporotic and osteoarthritic
      subjects.
AB  - The objective of this study was to evaluate the metabolic in vitro effect of the
      bisphosphonate neridronate on normal and pathological human osteoblasts. Primary
      human osteoblast cultures were obtained from cancellous bone of osteoarthritic
      (OA) and osteoporotic (OP) patients and a corresponding healthy control group.
      Osteocalcin production was evaluated by cultured cells in neridronate 10(-4) M
      and 10(-6) M, both under basal conditions and after vitamin D3 stimulation. In
      the absence of neridronate, vitamin D3 increased osteocalcin production in all
      cell cultures; under the same conditions, and in the absence of vitamin D3, OA
      osteoblasts showed a significantly higher osteocalcin production whereas OP
      osteoblasts showed a significantly lower osteocalcin production compared to the
      normal osteoblasts, respectively. In all cellular populations neridronate at a
      higher concentration (10(-4) M) induced a reduction in osteocalcin synthesis, but
      in normal and osteoarthritic osteoblasts did not reduce the stimulatory effect of
      vitamin D3, whereas it inhibited the vitamin D3-induced increase of osteocalcin
      synthesis in the osteoporotic cells. In normal and osteoporotic osteoblasts
      stimulation with the lower neridronate concentration (10(-6) M) significantly
      increased osteocalcin production, which was further enhanced by vitamin D3 as an
      additional effect of the combined treatment. In OA osteoblasts, neridronate 10(
      6) M did not induce an increase in osteocalcin synthesis and the additional
      effect of combined treatment with vitamin D3 was not observed. Neridronate can
      modify the metabolic activity of human osteoblasts by enhancing or decreasing
      their biosynthetic activity, both in normal and in pathological conditions,
      depending on compound concentration and on different cell types. These results
      confirm the validity of using neridronate at doses usually administered in
      treating osteoporosis, and they suggest using it to treat other diseases which
      show an altered osteoblast metabolism, such as osteoarthritis.

PMID- 16091842
TI  - The peptidylarginine deiminases expressed in human epidermis differ in their
      substrate specificities and subcellular locations.
AB  - Deimination, a post-translational modification catalyzed by peptidylarginine
      deiminases (PADs), appears as a crucial Ca(2+)-dependent event in the last steps
      of epidermal differentiation. In normal human epidermis, where the deiminated
      proteins are filaggrin and keratins, PAD1, 2 and 3 are expressed but their
      relative role is unknown. The three PADs, produced as active recombinant forms,
      showed distinct synthetic-substrate specificities, various efficiencies to
      deiminate filaggrin and particular calcium and pH sensitivities. Immunoelectron
      microscopy demonstrated that PAD1 and PAD3 are co-located with filaggrin within
      the filamentous matrix of the deeper corneocytes where the protein is deiminated.
      This result strongly suggests that both isoforms are involved in the deimination
      of filaggrin, an essential step leading to free amino acid production necessary
      for epidermal barrier function. Moreover, PAD1 was shown to persist up to the
      upper corneocytes where it deiminates keratin K1, a modification supposed to be
      related to ultrastructural changes of the matrix.

PMID- 16091843
TI  - Detailed molecular comparison between the inhibition mode of A/B-type
      carboxypeptidases in the zymogen state and by the endogenous inhibitor latexin.
AB  - Treatment of advanced stages of prostate carcinoma with histone-deacetylase
      inhibitors entails expression of human procarboxypeptidase-A4 (hPCPA4). The three
      dimensional structure of hPCPA4 has been solved and shows the features of related
      metallocarboxypeptidase zymogens, with a preformed alpha/beta/-hydrolase active
      enzyme moiety (hCPA4) and an inhibiting pro-domain (PD). The protease moiety
      recalls a sphere, out of which a spherical cone has been cut. This results in a
      funnel-like structure, at the bottom of which the active-site cleft resides. The
      border of this funnel is shaped by loops, which are responsible for the
      interaction with the PD, characterised by a large interface area and relatively
      few contacts. Such an inhibitory mode is evocative of the recently reported
      structure of the human inhibitor latexin in its complex with hCPA4. The main
      contacting structure of latexin is similar to the one employed for PD inhibition.
      In both cases, active-site blocking relies mainly on a loop provided by the
      central part of a beta sheet.

PMID- 16091844
TI  - Identification of functional genes during Fas-mediated apoptosis using a randomly
      fragmented cDNA library.
AB  - We describe a general strategy for the identification of functional genes that,
      when downregulated, result in a selectable phenotype. This strategy is based on
      expression selection of cDNA fragments that counteract their cognate genes. A
      cDNA library containing random fragments expressed in human HepG2, A375 and CLS
      354 cells was used to identify functional genes whose inhibition conferred
      resistance to Fas-induced apoptosis. Thirty-five clones were isolated, 28 of
      which were derived from unknown genes, that tagged 19 individual genes and 7 of
      which referred to known genes that tagged the apoptosis-related protein (APR)-1, 
      2 and indoleamine-pyrrole 2,3,-dioxygenase (IDO). The ability of APR-1-, -2- and
      IDO-derived antisense RNAs to induce resistance to Fas in HepG2, A375 and CLS-354
      cells suggested that APR-1, -2 and IDO genes are involved in the machinery of Fas
      mediated apoptosis. Our gene discovery strategy provides a generally applicable
      procedure to identify functional genes that interfere with apoptosis, and may
      therefore be clinically relevant for tumor therapy.

PMID- 16091845
TI  - Scaffolding microdomains and beyond: the function of reggie/flotillin proteins.
AB  - Reggie/flotillin proteins are considered to be components of lipid rafts and are
      commonly used as marker proteins for lipid microdomains. Yet almost a decade
      after their discovery, the function of reggies/ flotillins is still enigmatic. In
      this review we summarize the present state of knowledge on reggie/flotillin
      structure, localization and function, and discuss the role of the proteins in
      development and disease. Based on insights into reggie/flotillin function and by
      comparison with related proteins of the so-called SPFH
      (Stomatin/Prohibitin/Flotillin/HflK/C) protein family, including stomatin,
      podocin and prohibitin, we propose the existence of specific types of protein
      defined microdomains which are sculpt by the clustering of individual SPFH
      proteins. As 'specialized rafts' similar to caveolae, these membrane domains
      provide platforms for the recruitment of multiprotein complexes. Since, under
      certain circumstances, reggie-2/flotillin-1 translocates to the nucleus, reggie/
      flotillin microdomains are not only stable scaffolds but also dynamic units with
      their own regulatory functions.

PMID- 16091846
TI  - The effect of isoforms of the cell polarity protein, human ASIP, on the cell
      cycle and Fas/FasL-mediated apoptosis in human hepatoma cells.
AB  - Human ASIP (hASIP) is expressed as numerous alternative splicing isoforms and
      there is an atypical protein kinease C (aPKC) phosphorylation site in exon 17b of
      the encoded sequence. We have identified an important role for exon 17b in cancer
      cells. Our results showed that hASIP-sa and sb had different effects on cell
      growth and Fas/FasL-mediated apoptosis in BEL-7404 human hepatoma cells. Human
      ASIP-sa modified the S phase of the cell cycle and might stimulate cell
      proliferation. Growth inhibition by hASIP-a antisense oligonucleotide-confirmed
      the positive action of hASIP-sa. Compared with hASIP-sa, hASIP-sb accelerated
      Fas/FasL-induced apoptosis, examined by sub-G1 accumulation, chromatin
      condensation, nuclear fragmentation, PARP cleavage, caspase-8 degradation and
      mitochondria- regulated cell death. Treatment with aPKC inhibitor could enhance
      Fas/FasL-mediated apoptosis in hASIP-sa-overexpressing cells, suggesting that
      hASIP-sa and its interaction with aPKC might contribute to the malignant growth
      and the blocking of Fas/FasL-mediated apoptosis, while hASIP-sb might function as
      an antagonist of hASIP-sa.

PMID- 16091847
TI  - Function and molecular evolution of multicopper blue proteins.
AB  - Multicopper blue proteins (MCBPs) are multidomain proteins that utilize the
      distinctive redox ability of copper ions. There are a variety of MCBPs that have
      been roughly classified into three different groups, based on their domain
      organization and functions: (i) nitrite reductase-type with two domains, (ii)
      laccase-type with three domains, and (iii) ceruloplasmin-type with six domains.
      Together, the second and third group are often commonly called multicopper
      oxidases (MCOs). The rapid accumulation of genome sequence information in recent
      years has revealed several new types of proteins containing MCBP domains, mainly
      from bacteria. In this review, the recent research on the functions and
      structures of MCBPs is summarized, mainly focusing on the new types. The latter
      half of this review focusses on the two domain MCBPs, which we propose as the
      evolutionary intermediate of the MCBP family.

PMID- 16091848
TI  - The Influence of Mycobacterium tuberculosis sigma factors on the promotion
      efficiency of ptpAt promoter in Mycobacterium smegmatis.
AB  - It was found in a previous study that Mycobacterium tuberculosis protein tyrosine
      phosphatase ptpAt promoter is a highly active promoter in slow-growing species of
      mycobacteria, such as M. tuberculosis and M. bovis BCG, but inert in fast-growing
      mycobacterial species, such as M. smegmatis. This difference is presumed to be
      due to the differences between sigma factors systems of slow-growing pathogenic
      mycobacteria and the fast-growing saprophyte M. smegmatis. Therefore, we
      constructed a series of plasmids, named pOLYG-13x, which can express various M.
      tuberculosis sigma factors and also contain a P(ptpAt)-gfp reporter gene
      construct. By inducing different sigma factor genes of M. tuberculosis in M.
      smegmatis, we were able to explore the influences of various sigma factors on the
      expression efficiency of the ptpAt promoter. The result show that of the 10 sigma
      factors evaluated, only sigF and sigL were able to weakly drive the ptpAt
      promoter in M. smegmatis and other sigma factors were unable to drive the
      promoter.

PMID- 16091849
TI  - Occurrence of pS86/pEF47-related plasmids in gram-positive cocci.
AB  - A small, low-copy-number cryptic 5.5-kb plasmid, designated pEF47, was isolated
      from a rumen bacterium Enterococcus faecalis 47 and partially characterized.
      Comparisons by restriction and partial sequence analysis of pEF47 demonstrated
      high homology to pS86 plasmid, recently isolated from a human clinical strain E.
      faecalis S-86. PCR followed by sequence analysis and Southern hybridization
      showed that pS86/pEF47-related replicons are regularly encountered in plasmids
      from gram-positive cocci.

PMID- 16091850
TI  - News and notes: An atypical Campylobacter coli exhibiting unusual morphology.
AB  - Campylobacter coli cells are characterized by a comma, or spiral shape, and a
      single polar flagellum. Here we report stable spontaneous changes in morphology
      to an aflagellated straight rod. The ability to colonize the chick cecum was
      lost. The atypical cells were compared with the original C. coli 67 culture from
      which they were derived, with PCR, Riboprinting, and PFGE.

PMID- 16091851
TI  - Atypical genetic locus associated with the zwf gene encoding the glucose 6
      phosphate dehydrogenase from Enterococcus mundtii CRL35.
AB  - The zwf gene encoding glucose 6-phosphate dehydrogenase (G6PD, EC.1.1.1.49) from
      Enterococcus mundtii CRL35 was cloned as a 4921 bp EcoRI fragment and analyzed.
      The predicted zwf gene product consists of 506 residues with a molecular mass of
      58.4 kDa, and is fully active in Escherichia coli as demonstrated by its
      heterologous expression in the zwf-negative mutant E. coli Su294. It shows a high
      degree of sequence identity (40-60%) to G6PDs described in other bacteria.
      Upstream of the zwf gene, a homolog of the DtxR family was identified (ORF D).
      Analysis of the 5' sequence of ORF D revealed a potential promoter sequence,
      which would suggest the presence of an operon-like structure between ORF D and
      the zwf gene. Finally, it was found that Fe2+ levels have an important role as a
      modulator of G6PD activity. This is the first report of this type of regulation
      of G6PD activity. A possible involvement in oxidative stress is discussed.

PMID- 16091852
TI  - Ambulatory inguinal hernia repair with prolene hernia system (PHS).
AB  - Study was conducted to evaluate the feasibility and benefits of inguinal hernia
      repair with prolene hernia system (PHS) mesh under local anaesthesia as a day
      surgery procedure in a multinational society of United Arab Emirates. One hundred
      and seventy-eight inguinal hernias in 172 consecutive adults of whom 154 (89.5%)
      fitted the criteria of inclusion in the day-case surgery settings were operated
      upon including one early recurrence. Conversion from local to general anaesthesia
      was required in five (2.8%) patients. The mean operation time was 65 min,
      including the anaesthesia injection. The mean hospital stay was 2.1 days for all
      patients and 1.01 days for those who fitted in the ambulatory surgery program.
      Inguinal hernia repair using the PHS technique under local anaesthesia could be
      mastered by many of the surgeons in our hospital with minimal morbidity and short
      hospital stay with a potential to lessen recurrence.

PMID- 16091853
TI  - The association of partner abuse with risky sexual behaviors among women and men
      with HIV/AIDS.
AB  - Prior studies have found that partner abuse is related to risky sexual behavior.
      However, few studies have explored gender, sexual orientation, or substance use
      differences in this association, especially among people with HIV. We examined
      data from the Risk and Prevention survey from the HIV Cost and Services
      Utilization Study (HCSUS) sample on 726 sexually-active individuals in three
      gender/orientation groups (286 women, 148 heterosexual men, and 292 gay/bisexual
      men). The study assessed whether individuals with HIV who experienced or
      perpetrated abuse within a close relationship were likely to engage in
      unprotected intercourse with that same partner. Both abuse perpetration and
      victimization were significantly associated with having any unprotected
      intercourse. In multivariate tests, gender/orientation and substance use during
      sex moderated the perpetration effects. Secondary HIV prevention interventions
      need to take into account potentially abusive contexts in which sexual activity
      may occur for both men and women.

PMID- 16091855
TI  - Reducing the duration of untreated psychosis and changing help-seeking behaviour
      in Singapore.
AB  - AIM: This study was conducted to examine the impact of early detection strategies
      of an early psychosis intervention programme on the duration of untreated
      psychosis (DUP) and the pattern of help-seeking behaviour. METHOD: Patients with
      first-episode psychosis were compared before and after the initiation of a
      programme of public education and networking with primary health care providers.
      These two groups were compared on the DUP and the change in the pattern of help
      seeking. RESULTS: The DUP was significantly reduced from a median of 12 to median
      of 4 months (p=0.002, Mann-Whitney U-test). There was an increase in the
      proportion of self and family referrals, and a fall in the proportion of police
      referrals. CONCLUSION: Awareness campaigns which target multiple groups and use
      various modes of communication are effective in influencing the DUP and patterns
      of help-seeking.

PMID- 16091854
TI  - The effects of the going places program on early adolescent substance use and
      antisocial behavior.
AB  - This study evaluated the effects of a school-based intervention on growth
      trajectories of smoking, drinking, and antisocial behavior among early
      adolescents. Seven middle schools were randomized to intervention or comparison
      conditions and students in two successive cohorts (n = 1484) provided five waves
      of data from sixth to ninth grade. The Going Places Program, included classroom
      curricula, parent education, and school environment components. Latent growth
      curve analyses demonstrated significant treatment group effects, including
      reducing increases in friends who smoke, outcome expectations for smoking, and
      smoking progression, but had non-significant effects on drinking or antisocial
      behavior. The Going Places Program was effective in preventing increases in
      smoking progression, but its efficacy as a more cross-cutting problem behavior
      preventive intervention was not confirmed.

PMID- 16091856
TI  - Behavioural problems in Sri Lankan schoolchildren: associations with socio
      economic status, age, gender, academic progress, ethnicity and religion.
AB  - Little is known about behavioural and emotional adjustment in children in Sri
      Lanka, and this study is the first attempt to assess mental health problems in
      this population. Using the Strengths and Difficulties Questionnaire (Goodman R
      (1994) A modified version of the Rutter parent questionnaire including items on
      children's strengths: a research note. J Child Psychol Psychiatry 35:1483-1494)
      with parent, teacher and child informants, in a large sample of 10- to 13-year
      old school children from Colombo, we found rates and types of problems consistent
      with other international studies of child mental health. Problem rates were
      higher in boys and were associated with lower SES and poorer academic
      performance. Relationships between behavioural adjustment and Tamil ethnicity and
      Hindu religion emerged in this sample and could possibly be associated with the
      experience of longstanding ethnic conflict in Sri Lanka. The study confirms the
      need for development of child and adolescent health services in Sri Lanka.

PMID- 16091857
TI  - Predictors of suicide in a community-based cohort of individuals with severe
      mental disorder.
AB  - BACKGROUND: Rate of suicide is probably an indicator of the quality of mental
      health services within an area. The aim of this study was to identify predictors
      of suicide in a large community-based cohort of persons with long-term mental
      disorder. METHODS: A survey was conducted in Stockholm County, Sweden, in 1997 to
      identify adults with long-term disabling mental disorder (mental retardation and
      dementia excluded). The survey included an inventory of unmet needs as perceived
      by the service providers. The 12,247 cases were linked to the national in-patient
      register and the cause-of-death register. Predictors of suicide in 1997-2000 were
      determined by bivariate analysis and multiple logistic regression. RESULTS:
      Predictors of suicide included a history of in-patient psychiatric care, previous
      suicide attempt, substance abuse and unmet need of a contact person. Personality
      disorder, especially borderline personality disorder, was the strongest
      diagnostic predictor of suicide among those with a history of in-patient
      psychiatric care. CONCLUSION: Unmet needs may signal increased suicide risk in
      persons with severe mental disorder. Methods to improve suicide prevention in
      persons with personality disorder should be further developed. Interventions to
      reduce suicide in persons with a long-term mental disorder will require
      collaboration between psychiatric and social services.

PMID- 16091858
TI  - The prevalence of psychiatric disorders among 5-10 year olds in rural, urban and
      slum areas in Bangladesh: an exploratory study.
AB  - BACKGROUND: No previous epidemiological studies of child mental health have been
      conducted in Bangladesh, partly due to lack of suitable measures. METHODS: A
      Bangla translation of a standardised child psychiatric interview, the Development
      and Well-Being Assessment (DAWBA), was validated against routine clinical
      diagnoses on a consecutive series of 100 referrals to a child mental health
      service. A two-phase study of prevalence was applied to random samples of 5- to
      10-year-olds (N=922) drawn from three contrasting areas: a rural area, a
      moderately prosperous urban area, and an urban slum. RESULTS: There was
      substantial agreement between the DAWBA and the independent clinic diagnosis
      (kappa=0.63-0.94). The estimated prevalence of any ICD-10 diagnosis was 15% (95%
      CI 11-21%). The rate of obsessive-compulsive disorder was higher than in previous
      studies. Children from the slum area were significantly more likely to have
      serious behavioural problems, and marginally more likely to have post-traumatic
      stress disorder. CONCLUSION: A conservative extrapolation is that around 5
      million Bangladeshi children and adolescents have psychiatric disorders. In a
      country with very few child mental health professionals, there is a vast gap
      between need and provision that must be addressed.

PMID- 16091859
TI  - Is there a gender difference on the association between informal work and common
      mental disorders?
AB  - Economic activity in Brazilian women has been increasing in recent years,
      particularly in the form of under- and self-employment, which allows more
      flexibility in the work schedule and facilitates part-time work, a crucial issue
      for women reconciling family duties and the need for a remunerated occupation.
      This paper investigates the gender difference in the association between
      employment status and common mental disorders (CMD). A cross-sectional survey of
      a random sample of private households included 683 adults aged 15 years and over
      living in Olinda, Brazil. The self-reporting questionnaire (SRQ-20) was used to
      estimate the prevalence of CMD. The association between unemployment and CMD for
      men (OR=1.77, 95% CI 0.8-3.9) was in the same direction as that found for women
      (OR=2.66, 95% CI 1.1-6.3), but not significant. In contrast to this, while women
      working in the informal sector were more likely to be a case of CMD than formal
      workers (OR=3.02, 95% CI 1.3-7.2), no difference was found for informally working
      men (OR=1.08, 95% CI 0.5-2.4). The estimated OR for female informal workers was
      out of the 95% confidence intervals of the corresponding OR estimated for males,
      and the test for interaction was statistically significant (p=0.04). From a
      policy perspective, the value of encouraging people to take informal work depends
      both on how quickly individuals can be moved out of unemployment into informal
      work compared to other destinations, and how well individuals fare once in
      informal work. The results of the present study suggest that working outside the
      protection of employment legislation and with limited opportunity for skill use
      may be a risk for women's mental health.

PMID- 16091860
TI  - Comparing the stigma of mental illness in a general hospital with a state mental
      hospital: a Singapore study.
AB  - The stigma faced by psychiatric patients associated with the type of psychiatric
      facilities is controversial. This study was conducted to compare the stigma faced
      by patients with schizophrenia and non-schizophrenia psychiatric disorders in the
      outpatient departments of a state mental hospital with those in a general
      hospital in Singapore. A cross-sectional study involving two groups of
      outpatients in a state mental hospital (n=300) and in a university general
      hospital (n=300) were assessed with a 12-item stigma scale. Components of the
      scale assessed included social rejection, negative media perception, shame and
      social discrimination. Among schizophrenia patients, state mental hospital
      patients had significantly lower stigma scores compared to their counterparts in
      the general hospital. For other mental illnesses, the reverse was true: state
      mental hospital patients had significantly higher stigma scores compared to their
      counterparts in the general hospital. Stigma was also associated with a younger
      age and being employed though not by gender. The stigma faced by psychiatric
      patients is complex and may have institutional and disorder-specific elements.
      Possible reasons for this are discussed.

PMID- 16091861
TI  - IL-2 and IL-4 polymorphisms as candidate genes in schizophrenia.
AB  - An immune process, characterized by a relative predominance of the T helper-2
      (Th2) system and possibly induced by a viral infection,may be involved in the
      pathophysiology of schizophrenia. In this context, functional polymorphisms in
      the Interleukin-2 (IL-2) and Interleukin-4 (IL-4) genes appear to be principal
      candidates for genetic schizophrenia research. Further evidence for these
      candidate genes comes from several linkage analyses, pointing to susceptibility
      gene loci on chromosomes 4q and 5q, where the genes coding for IL- 2 and IL-4 are
      located. We carried out a case-control study including 230 schizophrenic patients
      and 251 healthy persons, investigating the IL-2 -330 T/G single nucleotide
      polymorphism (SNP) and the IL-4 -590 C/T SNP. A significant association of the IL
      2 -330 TT genotype and of the IL-4 -590 CC genotype with schizophrenia could be
      identified. Our findings may partly account for the relative predominance of the
      Th2 system in schizophrenia, although they cannot directly explain this
      immunological imbalance, but may be related to an altered antiviral immune
      response in patients with schizophrenia.

PMID- 16091862
TI  - Influence of striatal dopamine transporter availability on the response to
      methylphenidate in adult patients with ADHD.
AB  - In this study, we investigated whether availability of striatal dopamine
      transporter (DAT) may have an influence on the response of adult patients with
      attention deficit hyperactivity disorder (ADHD) on methylphenidate (MPH). In 18
      non-smoking and non-medicated adult patients with ADHD, availability of DAT was
      measured with [(99m)Tc] TRODAT-1 SPECT. Then, the patients received
      methylphenidate (MPH), individually titrated up to 60 mg per day. Ten weeks
      later, clinical improvement was rated by Clinical Global Impressions scale. In
      all, 6 patients were classified as non-responders, and 12 responded to MPH. From
      the non-responders, 5 presented with a DAT availability below that of normal
      controls of the same age, whereas in the group of responders all patients had
      elevated DAT availability. There was a significant negative correlation between
      values for global clinical improvement and striatal DAT availability. In
      conclusion, ADHD patients with low DAT availability seem not to respond to
      therapy with MPH.

PMID- 16091867
TI  - [In vitro tests for the determination of allergenic potency of "novel foods' and
      genetically modified organisms: relevance in vivo?].

PMID- 16091868
TI  - Early diagnosis of prostate cancer: the continuing debate on the impact on
      mortality.

PMID- 16091869
TI  - Bioethics, the Surviving Sepsis Campaign, and the industry.

PMID- 16091870
TI  - [The role of inflammation in the pathophysiology of acute coronary syndromes].
AB  - All stages of atherosclerotic plaques are characterized by an inflammatory
      component, in which T lymphocytes and macrophages orchestrate lesion progression
      and destabilization by releasing cytokines (e.g., interferon-gamma, tumor
      necrosis factor-alpha, tissue factor). At the extreme end of this process plaque
      rupture occurs, which may manifest clinically as an acute coronary syndrome.
      Hence, measuring this atherosclerosis-inherent inflammation may help predicting
      cardiovascular events. Accordingly, different soluble inflammatory markers were
      studied for their predictive value in acute coronary syndromes. Special attention
      was paid to high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand
      (sCD40L). The latter seems not only to be a marker of inflammation and platelet
      activation, but is suggested to directly destabilize atherosclerotic plaques by
      stimulating pro-inflammatory T lymphocytes. Therefore, reduction of soluble
      inflammatory markers is an attractive target for future therapeutic strategies.
      Statins and glycoprotein IIb/IIIa antagonists, well-established treatments in
      acute coronary syndromes, were demonstrated to decrease hs-CRP and sCD40L.
      Whether this reduction translates into a better prognosis has to be investigated
      in further studies.

PMID- 16091871
TI  - Apical ballooning syndrome.

PMID- 16091872
TI  - Prostate cancer and prostate-specific antigen (PSA) screening in Austria.
AB  - The possible effect of prostate-specific antigen (PSA) testing on prostate cancer
      mortality has remained controversial, despite the test's widespread application.
      We examined age-specific mortality trends for prostate cancer in Austria before
      and after the introduction of (opportunistic) PSA testing, to ask whether PSA
      screening reduces prostate cancer mortality in a uniform cohort of men with equal
      access to health care. Prostate cancer mortality data covering all 9 federal
      states of Austria were analysed from 1970 to 2002. PSA testing became widely
      available in Austria not before 1989. Tyrol, one of the nine federal states of
      Austria, independently launched a mass prostate cancer prevention project in
      1993. We applied join-point regression models to identify changes in the slope of
      age-specific mortality trends in selected age groups (50-59, 60-69, 70-79, and 80
      89 years) and calculated the annual percent change (APC) in mortality between
      1970 and 2002 for Tyrol and the rest of Austria separately. After 12 years of
      follow-up, we were not able to observe a significant reduction in prostate cancer
      mortality since the introduction of the PSA test in the age groups of 50-59, 60
      69, and 80-89 years. A significant decrease was found in the age group of 70-79
      (Austria without Tyrol 1989 through 2002: APC, -2.36; 95% CI, -3.38 to -1.34;
      Tyrol 1991 through 2002: APC, -6.42; 95% CI, -8.92 to -3.86). In this age group
      the join points 1989 and 1991 cannot be related to PSA testing. PSA screening
      does not appear to reduce prostate cancer mortality in a uniform cohort of men
      with equal access to health care. However, given the long lead-time for prostate
      cancer, even longer follow-up may still be needed to detect any important trends.

PMID- 16091873
TI  - Impact of disease severity on quality of life in adults with asthma.
AB  - Health-related quality of life is increasingly used as an outcome measure in
      asthma. The aim of this study was to define the relationship between asthma
      symptoms, lung function and health related quality of life in a community based
      sample of people with asthma ranging from no recent asthma to severe persistent
      asthma. We recruited subjects at the age of 42 years from a well-described
      community cohort, the Melbourne Epidemiological Study of Childhood Asthma, to
      define this association. 161 subjects completed a respiratory symptom survey, the
      Asthma Quality of Life Questionnaire and had lung function testing. According to
      the previous surveys and when applicable in agreement with GINA, subjects were
      classified into 4 groups: no recent asthma, sporadic asthma, intermittent asthma
      and persistent asthma, with the persistent asthma group further categorised by
      wheezing frequency and lung function. 55 had no recent asthma, 31 had sporadic
      asthma, 39 had intermittent asthma and 36 had persistent asthma. There was clear
      evidence of lower total scores with increased asthma severity, with median scores
      of 6.8 for the sporadic asthma group, 6.4 for the intermittent and 5.5 for the
      persistent asthma group compared to 6.9 in those with no recent asthma. All
      domain scores within the intermittent and persistent asthma groups were lower
      than scores for the no recent asthma group (p < 0.01). Those with persistent
      asthma and low FEV1% had the lowest quality of life scores (4.6). Analysis of
      this population cohort highlights that health related quality of life in patients
      with asthma strongly depends on symptom frequency and lung function and
      underlines the necessity of adequate treatment.

PMID- 16091874
TI  - Trends in educational and occupational differentials in all-cause mortality in
      Austria between 1981/82 and 1991/92.
AB  - Comparative international studies regularly find an increase in mortality
      differentials by education and socioeconomic group. We are interested in whether
      the same is true for Austria, a country for which no previous comparable study
      exists. On the basis of linked death and census records for the Austrian
      population in the years 1981/82 and 1991/92, we observed a widening gap in
      educational and occupational differentials of Austrian men in relative and
      absolute mortality from all causes. The increase was restricted to ages 50 to 74,
      whereas mortality differentials at younger and older ages were unchanged or
      slightly lower. The growing gap resulted from increasing mortality advantages for
      men with tertiary education, the highest educational group. Their absolute
      mortality and relative mortality risks decreased faster than those of all other
      educational groups. Educational differentials among women remained unchanged.

PMID- 16091875
TI  - Initial experience with oral valganciclovir for pre-emptive cytomegalovirus
      therapy after lung transplantation.
AB  - BACKGROUND: The most common opportunistic viral pathogen after lung
      transplantation is cytomegalovirus (CMV). Oral valganciclovir, a prodrug of
      ganciclovir, has been introduced as a potential drug for prophylaxis and
      treatment of CMV infection and disease in lung transplantation. The goal of this
      study was to describe our initial experience with oral valganciclovir for pre
      emptive treatment of CMV infections after lung transplantation. METHODS AND
      PATIENTS: We summarize our experience with 19 patients who underwent lung
      transplantation and received pre-emptive oral valganciclovir therapy in the
      situation of positive CMV polymerase chain reaction (PCR) in either plasma or
      bronchoalveolar lavage. None of the patients presented with manifest CMV disease.
      Treatment dosage of valganciclovir was 450 mg to 1800 mg daily, depending on
      renal function and white blood count. Treatment was continued until the CMV PCR
      became negative, in any case for a period of at least 14 days. RESULTS: Three
      patients received two courses of pre-emptive oral valganciclovir; 16 patients
      were treated once. Eleven patients (57.9%) were treated because of a positive
      plasma CMV PCR; in eight patients (42.1%) the PCR was positive only in
      bronchoalveolar lavage. Therapy was initiated 896 +/- 1186 days (range, 108-3911)
      after transplantation with a mean CMV PCR of 45,536 +/- 149,294 copies (range,
      426-706,000). In all cases the PCR fell below detectability (<400 copies) after a
      period of 22 +/- 10 days of treatment (range, 7-50 days). Mild to moderate
      leucopenia was observed in seven patients (36.8%) during treatment. None of the
      patients developed new onset of other potentially drug-related disorders such as
      neutropenia, anemia, deterioration of renal function or gastrointestinal
      disorder. CONCLUSIONS: Pre-emptive therapy with oral valganciclovir for CMV
      infections detected by PCR in either plasma or bronchoalveolar lavage after lung
      transplantation seems to be efficacious and safe. However, regular blood counts
      should be performed to detect developing leucopenia.

PMID- 16091876
TI  - Plasma levels of polyunsaturated fatty acids in children with atopic dermatitis
      and in atopic and nonatopic controls.
AB  - BACKGROUND: Atopic dermatitis has been thought to be associated with a
      disturbance in n-6 polyunsaturated fatty acid (PUFA) metabolism, but randomized
      trials investigating the clinical efficacy of oral supplementation with
      gammalinolenic acid have revealed conflicting results. AIM OF THE STUDY: To re
      investigate the proposed linkage between PUFA dysregulation and atopic
      dermatitis. MATERIALS AND METHODS: Plasma levels of linoleic acid (LA),
      gammalinolenic acid (GLA), dihomogammalinolenic acid (DGLA) and arachidonic acid
      (AA) were measured using HPLC in 22 children with atopic dermatitis. Patients
      were subdivided into those with elevated total serum IgE (group A, n = 15, IgE >
      +1 SD of age-specific normal values) and those with normal IgE (group B, n = 7)
      and compared with children suffering from allergic rhinitis/asthma (group C, n =
      8) and with non-atopic controls (group D, n = 6). RESULTS: GLA levels were
      significantly lower (p < 0.05) in eczema patients with elevated IgE (A, 0.19 +/-
      0.06%) and in atopic controls (C, 0.23 +/- 0.06%) than in eczema patients with
      low IgE (B, 0.42 +/- 0.19%) and non-atopic controls (D, 0.43 +/- 0.16%). There
      were no significant differences between groups for LIN, DGLA and AA, except for
      lower LIN levels in atopic controls. Correlation of individual LA and GLA values
      showed significantly steeper regression lines in low-IgE responders (B and D,
      k(x) = 0.058) than in high-IgE responders (A and C, k(x) = 0.012; p < 0.02),
      suggesting impaired delta-6-desaturase function in the latter. For the study
      population as a whole, there was a clear negative correlation between total
      levels of IgE and GLA (r(s) = -0.64) and a moderate negative correlation between
      total IgE and AA (r(s) = -0.38). CONCLUSIONS: Dysregulation of n-6 PUFA
      metabolism is neither consistently found in nor specifically associated with
      atopic dermatitis but rather appears to be associated with IgE production and
      atopy in general. The finding of decreased GLA levels in eczema patients with
      elevated total IgE and in children with allergic rhinitis and asthma but not in
      eczema patients with normal total IgE questions the proposed pathophysiologic
      role of fatty acid dysregulation in atopic dermatitis.

PMID- 16091877
TI  - [Appendix vermiformis duplex--a rare surprise].
AB  - Duplication of the vermiform appendix is extremely rare. It is found in only
      1/25.000 patients (0.004%) operated on for acute appendicitis. A 60-year-old male
      patient was hospitalized for a peridiverticular sigmoid abscess without signs of
      a free abdominal perforation and an abscess cavity in the small pelvis. A
      Hartmann's resection and an appendectomy (the vermiform appendix was part of the
      abscess wall) were performed. The pathology report described an external
      appendicitis. After 3 months, the intestine was successfully reanastomosed.
      During mobilisation of the coecum, a second retrocoecal vermiform appendix was
      surprisingly found. Because of signs of a chronic appendicitis a second resection
      was performed. Although the diagnosis of an appendix duplex is a rarity, surgeons
      should be aware of the possibility, especially when clinical signs and symptoms
      point to appendicitis, although at laparotomy the appendix looks normal. A
      routine exploration for a second appendix is definitely not indicated because of
      the rarity and the increased complication rate.

PMID- 16091878
TI  - Herpes simplex virus infection limited to the brainstem.
AB  - Focal meningoencephalitis is commonly caused by Herpes simplex virus infection,
      which typically affects temporal or frontal lobes, and carries a mortality rate
      of 70% if untreated. On rare occasions, however, the infection is restricted to
      the brain stem. Polymerase chain reaction analysis of cerebrospinal fluid is the
      gold standard for the diagnosis of herpes simplex encephalitis. A 46-year-old
      male was admitted to the hospital with a three-day history of headache and fever
      up to 39 degrees C. Cerebrospinal fluid findings were in accordance with aseptic
      meningitis. On the third hospital day, the patient presented with double vision
      followed by confusion, and gaze paresis developed. The condition rapidly
      progressed from stupor to coma. A second examination of cerebrospinal fluid
      revealed a low glucose level (1.2 mmol/l) and cefotaxime with ampicillin were
      started empirically. All cerebrospinal fluid specimens were negative for bacteria
      and fungi. Serum IgG antibodies for herpes simplex virus type 1 were found with
      no intrathecal specific antibody synthesis. A polymerase chain reaction analysis
      of cerebrospinal fluid sample performed on the seventh day of his illness was
      negative for herpes simplex virus 1 and 2. A computer tomography scan of the
      brain did not show any abnormality. Despite antimicrobial and supportive
      intensive care, the condition of the patient progressively deteriorated and he
      died on the 11th day after admission. An autopsy revealed hemorrhagic and
      necrotic brainstem meningoencephalitis, and herpes simplex virus type 1 infection
      was confirmed by hybridization in situ. Herpes simplex virus encephalitis carries
      a mortality rate of 70% if untreated. The atypical location of the infection, as
      well as an atypical clinical manifestation with negative radiological and
      microbiological tests, could be the reasons for false diagnoses and mistreatment.
      Many authors advocate the use of empiric acyclovir in any patients with
      unexplained encephalopathy, since delay in treatment may greatly affect outcome.
      We describe a patient who died due to a herpes simplex virus 1 encephalitis
      affecting the brainstem, where nucleic acids were found post mortem by in situ
      hybridization. On rare occasions, the herpes simplex viral infection, as well as
      clinical manifestations and pathological changes, is restricted solely to the
      brainstem.

PMID- 16091879
TI  - Anthroposophic therapy of respiratory and ear infections.

PMID- 16091881
TI  - Expression and purification of N and E proteins from severe acute respiratory
      syndrome (SARS)-associated coronavirus: a comparative study.
AB  - Histidine-tagged N (rNH) and E (rEH) proteins of Severe Acute Respiratory
      Syndrome (SARS)-coronovirus were expressed in the baculovirus/insect cell system
      and purified by immobilized metal affinity chromatography. rNH and rEH proteins
      differed markedly with respect to expression levels, cell death kinetics and
      subcellular localizations that led to different extraction and purification
      schemes. The features of both proteins are compared and the potential
      applications of purified rNH and rEH are discussed.

PMID- 16091882
TI  - A sericin-derived peptide protects sf9 insect cells from death caused by acute
      serum deprivation.
AB  - Sericin is the silk protein enveloping fibroin fibers in cocoons. Sericin
      hydrolysate protects cultured Sf9 insect cells from death caused by serum
      deprivation; the activity depends on the repeats of 38 amino acids. A partial
      peptide from the 38 residues, SGGSSTYGYS, inhibited serum-deprivation death as
      well. Cell viabilities in the presence of 10% (v/v) foetal calf serum, no
      additives and 1 mM: SGGSSTYGYS were 96, 12 and 31% on the third day after
      inoculation, respectively. Aromatic residues seemed to be important because
      SGGSSTWGWS had the same activity as SGGSSTYGYS but SGGSSTAGAS had no activity.

PMID- 16091883
TI  - Stable transformation of embryogenic tissues of Pinus nigra Arn. using a
      biolistic method.
AB  - The stable transformation of embryogenic tissues of Pinus nigra Arn., cell line
      E104, has been achieved using a biolistic approach. The introduced DNA consisted
      of the uidA reporter gene under the control of the double CaMV 35S promoter and
      the nptII selection gene controlled by the single CaMV 35S promoter. Three days
      after bombardment, putative transformed tissues were selected for continued
      proliferation on a medium containing 20 mg geneticin l(-1). Resistant embryogenic
      tissue recovery required 10-12 weeks. The integration of the nptII and uidA genes
      was confirmed by both histochemical/fluorimetric GUS assays and PCR amplification
      of the inserts in the five geneticin resistant sub-lines of line E104. The
      activity of the uidA reporter gene in transgenic, embryogenic tissue lines was
      stable and could be detected after one year of culture. Somatic embryo maturation
      was, however, poor and no plantlet regeneration could be obtained.

PMID- 16091884
TI  - Purification and characterization of recombinant truncated human interleukin-11
      expressed as fusion protein in Escherichia coli.
AB  - Mature human interleukin-11 (HuIL-11) is a cytokine consisting of 178 amino acid
      residues that results from scission of the N-terminal signal peptide, consisting
      of 21 amino acid residaues, from the corresponding nascent polypeptide. A DNA
      fragment encoding a truncated HuIL-11 (trHuIL-11), with an additional 5 amino
      acid residues removed from the N-terminus, was cloned into vector pGEX-2T between
      the BamHI site and the EcoRI site. Upon transformation with Escherichia coli
      BL21, the construct over-produced a glutathione S-transferase (GST)-fused protein
      in a soluble form after IPTG induction. The fusion protein was initially
      fractionated with butyl-Sepharose 4 fast flow column and by affinity
      chromatography using a GSH-Sepharose 4B column. On-site enzymatic release with
      thrombin gave the target protein at 96% purity as judged by SDS-PAGE and HPLC.
      Expression of the interleukin as a GST-fused protein thus greatly improved
      downstream processing. Subsequent biological activity assay suggested that trHuIL
      11 had similar activity profile to the naturally produced sample and may be a
      promising candidate for further development as biopharmaceutical.

PMID- 16091885
TI  - Induction of glutathione S-transferase and glutathione by toxic compounds and
      elicitors in reed canary grass.
AB  - Treatment of read canary grass leaves with phenol, 4-chlorophenol, naphthalic
      anhydride and phenylethylisothiocyanate increased glutathione S-transferase
      activity by 1.4-2.4-fold (control 17 U g(-1) DW). Benzothiadiazole, beta
      aminobutyric acid and salicylic acid increased activity by 1.3-1.8-fold. Total
      glutathione pool was increased by the toxic compounds by 1.2-2-fold and by the
      elicitors 1.4-1.6-fold (control 593 nmol g(-1) DW). Unlike the other compounds,
      benzothiadiazole and salicylic acid did not decrease the redox state.
      Benzothiadiazole acted synergistically with chlorophenol on glutathione S
      transferase and glutathione levels and counteracted the decrease in redox state
      caused by the xenobiotic. Reed canary grass thus has a strong potential to
      neutralize toxic compounds, which may be further enhanced by elicitors.

PMID- 16091886
TI  - Regulation of gamete release in the economic brown seaweed Hizikia fusiforme
      (Phaeophyta).
AB  - Gamete release is an essential event in artificial seeding of the economic brown
      seaweed, Hizikia fusiforme. Mass egg release occurred in the dark, with few eggs
      being discharged in the light. Release of eggs was elicited with eight practical
      salinity units (one PSU identical with 1 g sea salts l(-1)) and was inhibited by
      salinity levels >32 PSU. Egg release was optimal at 23 degrees C, and was
      decreased by 72% in agitated seawater compared to unstirred seawater. Inhibitors
      of photosynthesis and ions channels suppressed egg release, indicating that this
      process was physiologically associated with photosynthetic activity and ion
      transport.

PMID- 16091887
TI  - Monitoring and quantification of inclusion body formation in Escherichia coli by
      multi-parameter flow cytometry.
AB  - Multi-parameter flow cytometry was used to monitor the formation of
      promegapoietin (PMP) inclusion bodies during a high cell density Escherichia coli
      fed-batch fermentation process. Inclusion bodies were labelled with a primary
      antibody and then with a secondary fluorescent antibody. Using this method it was
      possible to detect PMP inclusion body formation with a high specificity and it
      was possible to monitor the increased accumulation of the protein with process
      time (6-48 mg PMP/g CDW) whilst highlighting population heterogeneity.

PMID- 16091888
TI  - Secretion of hepatitis B surface antigen in transformed tobacco cell suspension
      cultures.
AB  - Six different expression cassettes of hepatitis B surface antigen (HBsAg) were
      used to transform tobacco cell suspension cultures. The transgenic nature of the
      cells was confirmed by PCR. The secreted HBsAg was assayed by ELISA and analyzed
      by Western blotting. A maximum of 31 microg antigen/l was obtained in the spent
      medium from the transformed cells. The use of an ethylene-forming enzyme promoter
      and incorporation of C-terminal endoplasmic-reticulum-retention signal enhanced
      the secretion of HBsAg. Salicylic or jasmonic acid at 10 microM: increased
      secretion of HBsAg by six fold.

PMID- 16091889
TI  - Cultivation of microorganisms in the cultural medium made from squid internal
      organs and accumulation of polyunsaturated fatty acids in the cells.
AB  - The disposal and more efficient utilization of marine wastes is becoming
      increasingly serious. A culture media for microorganisms has been prepared from
      squid internal organs that are rich in polyunsaturated fatty acids (PUFAs). Both
      freshwater and marine bacteria grew well in this medium and some bacteria
      accumulated PUFAs in their lipids, suggesting uptake of exogenous PUFAs. Higher
      PUFA accumulations were observed in Escherichia coli mutant cells defective
      either in unsaturated fatty acid biosynthesis or fatty acid degradation, or both,
      compared to those without these mutations. Therefore, PUFA accumulation in cells
      can be improved by genetic modification of fatty acid metabolism in the bacteria.
      Squid internal organs would be a good source of medium, not only for marine
      bacteria but also for freshwater bacteria, and that this process may be
      advantageous to make efficient use of the fishery wastes and to produce PUFA
      containing microbial cells and lipids.

PMID- 16091890
TI  - Bacterial Cr(VI) reduction concurrently improves sunflower (Helianthus Annuus L.)
      growth.
AB  - Four Cr(VI)-reducing bacterial strains (Ochrobactrum intermedium, CrT-2, CrT-3
      and CrT-4) previously isolated from chromium-contaminated sites were inoculated
      on to seeds of sunflower (Helianthus annuus var SF-187), which were germinated
      and grown along with non-inoculated controls with chromate salts (300 microg
      CrCl3 or K2CrO4 ml(-1)). Severe reduction (20%) in seed germination was observed
      in Cr(VI) stress. Plant height decreased (36%) with Cr(VI) when compared with
      chromium-free control, while O. intermedium inoculation resulted a 20% increment
      in this parameter as compared to non-inoculated chromium-free control. CrT-3
      inoculation resulted a 69% increment in auxin content as compared to non
      inoculated control. O. intermedium caused 30% decrease in chromium uptake in
      sunflower plant roots under Cr(VI) stress as compared to chromium-free control
      plants.

PMID- 16091891
TI  - Autohydrogenotrophic denitrifying microbial community in a glass beads biofilm
      reactor.
AB  - A glass bead biofilm reactor was operated using H2 as an electron donor to remove
      nitrate at 150 mg NO3-N l(-1) to below detection level. The microbial community
      in the glass beads biofilm reactor was investigated by using denaturing gradient
      gel electrophoresis (DGGE) and phylogenetic analysis. In DGGE analysis of the
      biofilm, five bands were dominant and indicated the presence of eight beta
      proteobacteria, one gamma-proteobacteria and twelve clostridia. An unculturable
      Hydrogenophaga sp., which is a new genus of hydrogen-oxidizing bacterium was
      dominant in microbial community of the biofilm reactor.

PMID- 16091892
TI  - Carbon and nitrogen sources influence the ligninolytic enzyme activity of
      Trametes versicolor.
AB  - Among carbon sources studied, cellobiose and mannitol provided the highest
      laccase (Lac) activity (648 and 742 U1(-1), respectively) of Trametes versicolor
      775 while glucose gave maximum manganese peroxidase (MnP) and peroxidase
      activities (44 and 114 U1(-1), respectively). Citrus fruit peel as growth
      substrate enhanced Lac activity 7-fold when compared to the medium with
      cellobiose, whereas grape vine sawdust increased MnP and peroxidase activity up
      to 148 and 677 U1(-1), respectively.

PMID- 16091894
TI  - INFECTION - a mirror of the wide field of infectious diseases.

PMID- 16091895
TI  - Starting or changing therapy - a prospective study exploring antiretroviral
      decision-making.
AB  - BACKGROUND: When to start or change antiretroviral treatment against HIV
      infection is of major importance. Patients' readiness is considered a major
      factor influencing such treatment decisions, in particular because no objective,
      absolute time point when to start antiretroviral therapy exists. We aimed at
      evaluating patients' readiness to start or change antiretroviral therapy (ART).
      PATIENTS AND METHODS: HIV-infected patients starting or changing ART between July
      2002 and February 2003, treating physicians and nurses participated in this
      prospective, observational multicenter study. We assessed shared decision-making
      including qualitative aspects, expected treatment decisions and treatment status
      after 3 months. RESULTS: 75 patients were included. Of 34 patients for whom
      starting ART was considered, 27 (79%) indicated that they were willing to start
      treatment. After 3 months, 21 of 27 (78%) actually started therapy, six did not.
      Patients with depression were less likely to be ready for ART (p < 0.05). Of 41
      patients for whom changing ART was considered, 35 (85%) indicated that they were
      willing to change treatment. Of the latter 35 patients, 33 (94%) finally changed
      ART within 3 months. Physicians and nurses were too optimistic in predicting the
      start or change of ART. The main reason to start or change ART was the sole
      recommendation of the physician (52% in those starting, 61% in those changing
      ART). Patients mainly judged the decision as shared and were very satisfied (71%)
      with the process. Qualitative findings revealed the importance of a dialectic
      decisionmaking, described with two categories: "dealing with oneself and others"'
      and "understanding and being understood." CONCLUSION: Patients mainly shared the
      decision made during consultation. Although physicians have an essential role
      concerning ART, patients, physicians, and nurses all contribute to the decision.
      Qualitative findings indicate the importance for health-care providers to include
      patients' expertise and contributions.

PMID- 16091896
TI  - Diagnostic and prognostic values of admission procalcitonin levels in community
      acquired pneumonia in an intensive care unit.
AB  - BACKGROUND: Measurement of procalcitonin (PCT) has been studied for several years
      in infectious diseases. Some studies have focused on community-acquired pneumonia
      (CAP) but only one was conducted in critically ill patients hospitalized in an
      intensive care unit (ICU). PATIENTS AND METHODS: To determine the diagnostic and
      prognostic role of PCT in patients admitted in an intensive care unit for severe
      CAP, 110 patients hospitalized in our unit were prospectively studied. Within 48
      hours following ICU admission, PCT serum level was measured with a quantitative
      method above a threshold value of 0.5 ng/ml. RESULTS: Initially focusing on the
      diagnostic value of PCT, 20% of the patients had a serum PCT level <0.5 ng/ml,
      30% between 0.5 ng/ml and 2 ng/ml, and 50%>/=2 ng/ml. Serum PCT level was higher
      in microbiologically documented CAP (median=4.9 ng/ml vs 1.5 ng/ml if no bacteria
      were found; p=0.001), but was not predictive of any specific bacterial agent.
      Concerning the prognostic value, the serum PCT level was higher for bacteremic
      patients and/or septic shock patients (4.9 ng/ml vs 1.5 ng/ml; p=0.0003).
      Moreover, PCT levels were increased in patients who developed, during their ICU
      stay, infection-related complications (septic shock, multiorgan dysfunction,
      acute respiratory distress syndrome and disseminated intravascular coagulation).
      Finally, the initial PCT level was significantly higher in patients who died
      during the ICU stay (5.6 ng/ml vs 1.5 ng/ml; p<0.0001). Such a relationship was
      not found with C-reactive protein (CRP). CONCLUSION: In ICU patients admitted for
      severe CAP, initial PCT values could be an interesting predictor for
      complications and mortality.

PMID- 16091897
TI  - Cerebrospinal fluid adenosine deaminase levels and adverse neurological outcome
      in pediatric tuberculous meningitis.
AB  - BACKGROUND: There is a lack of data on the prognostic significance of changes in
      cerebrospinal fluid (CSF) parameters in tuberculous meningitis. Our objective was
      to determine whether changes in CSF parameters are associated with poor
      neurological outcome in tuberculous meningitis. PATIENTS AND METHODS: We
      conducted a prospective cohort study on children admitted with a diagnosis of
      tuberculous meningitis to Government General Hospital in Kakinada, India. On
      admission, CSF parameters including cell count with fraction of lymphocytes and
      neutrophil leukocytes, glucose, protein, lactic dehydrogenase (LDH), and
      adenosine deaminase (ADA) levels were measured. We compared levels in children
      with and without adverse neurological outcome. RESULTS: A total of 26 children
      was enrolled over a 2-year period. Ten had an adverse neurological outcome. Six
      had permanent neurological deficits (four hemiplegia and two cranial nerve
      palsies), two a hydrocephalus and two died. There was no significant (p>0.05)
      difference in age, gender and in CSF parameters, including cell count, lymphocyte
      and neutrophil leukocyte fraction, glucose, protein, and LDH levels between
      patients with and without adverse neurological outcome. Patients with adverse
      outcome had with a mean (SD) of 17.1 (3.2) IU/l a significantly higher ADA level
      than patients without, who had a mean (SD) level of 11.3 (2.7) IU/l (p<0.001, t
      test). CONCLUSION: Adverse neurological outcome in childhood tuberculous
      meningitis is associated with increased cerebrospinal fluid adenosine deaminase
      levels.

PMID- 16091898
TI  - Increase of fungal endocarditis in children.
AB  - BACKGROUND: Infective endocarditis (IE) is a rare and feared infection that
      mainly occurs in patients with underlying cardiac disease or altered function of
      the immune system. Recent epidemiological data on both sepsis and nosocomial
      infections indicate a rise in gram-negative bacterial and fungal infection,
      particularly in patients requiring critical care support. This study sought to
      characterize the change in the spectrum of IE encountered in a single pediatric
      tertiary care center during the last 18 years, to evaluate emergence of fungal IE
      and to identify contributing factors. PATIENTS AND METHODS: Review of all cases
      of IE diagnosed between January 1986 and August 2003 at a single university
      children's hospital. Patients were distributed between two equal time periods and
      compared according to the era of IE diagnosis. RESULTS: In 43 patients, 44
      episodes of IE were identified with most cases occurring in children with
      congenital or acquired heart disease. The annual number of diagnosed cases
      fluctuated during the study (mean 2.4 cases/year). Blood or specimen cultures
      were positive in 34 cases (77%) with gram-positive organisms most frequently
      observed (n=20, 44.4%). Fungal IE cases (n=9, 20%) occurred preferentially during
      the second period (p<0.03), and were more common in children with noncardiac
      diseases (p=0.023). Factors associated with fungal IE were the use of broad
      spectrum antibiotics (p<0.001) and the presence of an infected central venous
      catheter (p=0.01). Overall mortality did not differ between the two eras.
      CONCLUSION: The incidence of fungal IE seems to have significantly increased in
      more recent years. Use of broadspectrum antibiotics for prolonged time or/and
      central venous catheters were identified as predisposing factors to fungal
      infective endocarditis.

PMID- 16091899
TI  - Transregional spread of a single clone of methicillin-resistant Staphylococcus
      aureus between groups of drug users in Switzerland.
AB  - BACKGROUND: An epidemic spread of methicillin-resistant Staphylococcus aureus
      (MRSA) among intravenous drug users (IDUs) has been observed in Zurich. In the
      present study we investigated the situation in the Grisons, Switzerland. PATIENTS
      AND METHODS: We screened IDUs and their caregivers in medical and socio
      therapeutical institutions in the Grisons for MRSA. Nose swabs were used for
      bacterial culture and pulsed-field gel electrophoresis for MRSA genotyping.
      RESULTS: A total of 191 nose swabs from 111 IDUs and 80 caregivers was analyzed.
      None of the caregivers was MRSA positive. Six IDUs were asymptomatic MRSA
      carriers (5.4%). They participated in the official heroin program (MRSA
      prevalence in this group 16%). The MRSA genotype was identical with the single
      clone found in IDUs in Zurich, strongly suggesting an epidemic spread.
      Decolonization was successful in two persons only. Persistence of MRSA in IDUs
      must therefore be assumed. CONCLUSION: We conclude that a single clone of MRSA,
      found in IDUs in Zurich, has spread to a distant region of Switzerland. A
      rigorous infection control program in all institutions with IDUs is necessary to
      prevent a further spread of MRSA.

PMID- 16091900
TI  - Localized pulmonary infection associated with Mycobacterium tilburgii in an HIV
      infected patient.
AB  - The case of an HIV-infected patient with low CD4+ cell count and localized
      pulmonary infection associated with Mycobacterium tilburgii, a recently
      recognized atypical mycobacterial species, is reported. Diagnosis was confirmed
      by repeated detection of mycobacterial DNA in lung biopsy specimens. After
      surgical removal of the pulmonary nodules, treatment with antimycobacterial
      combination therapy led to a complete and sustained recovery of the respiratory
      symptoms.M. tilburgii so far has only been described to cause disseminated
      infection in three patients, two of them suffering from acquired immunodeficiency
      syndrome. To our knowledge, this is the first report of localized pulmonary
      disease attributed to this mycobacterial species. As it responds to
      antimycobacterial combination therapy, efforts to establish the diagnosis using
      PCR methods in patients with suspected pulmonary disease due to mycobacteria
      other than tuberculosis should be undertaken.

PMID- 16091901
TI  - Cryptococcus neoformans peritonitis in a patient with alcoholic cirrhosis: case
      report and review of the literature.
AB  - In the absence of coexisting HIV infection Cryptococcus neoformans is rarely
      considered in the differential diagnosis of peritonitis that occurs in patients
      with cirrhosis and ascites. Here, we report on a 39-year-old male, HIV-negative
      patient with decompensated alcohol toxic liver cirrhosis who developed a lethal
      intraperitoneal infection with C. neoformans. We reviewed the literature and
      found an additional 19 cases with culture confirmed cryptococcal peritonitis in
      combination with liver disease or AIDS. We suggest that awareness of this unusual
      but lethal entity may lead to earlier diagnosis and proper treatment.

PMID- 16091902
TI  - Infection by a dimorphic fungus Sporothrix schenckii in an immunocompromised
      patient.
AB  - Infections caused by dimorphic fungi, rarely observed in a temperate climate, may
      cause chronic infections in immunocompromised patients. We describe a case of
      sporotrichosis in a 50-year-old woman, who underwent mastectomy due to breast
      carcinoma, followed by radiation and chemotherapy. She developed skin lesions,
      localized along the lymphatics. Discharge samples repeatedly yielded a
      characteristic growth of the dimorphic fungus Sporothrix schenckii. The isolate
      was resistant to all commonly used antifungal agents, except for itraconazole.
      Therapy with this antifungal agent resulted in disappearance of the clinical
      symptoms.

PMID- 16091903
TI  - Coinfection of Schistosoma mansoni and Strongyloides stercoralis in a patient
      with variceal bleeding.
AB  - We report a case of hepatosplenic schistosomiasis with portal hypertension and
      variceal bleeding in an immigrant patient from Egypt, coinfected with
      Strongyloides stercoralis. The diagnosis was based on the following: (a)
      identification of Schistosoma mansoni ova in the stools and colonic biopsy
      specimens, (b) portal hypertension and esophageal varices with normal liver
      function and the absence of hepatic cirrhosis stigmata, (c) history of migration
      from an endemic area and (d) ultrasonographic findings of spleen and liver
      enlargement, fibrosed portal tracts, and normal lobular architecture of liver
      parenchyma. Hepatosplenic schistosomiasis should be suspected in any patient from
      an endemic area who has splenomegaly, portal hypertension, and esophageal varices
      bleeding in the absence of stigmata of liver cirrhosis and hepatic insufficiency.
      Coinfection with S. stercoralis could be attributed to common epidemiological
      features of the parasites and the patient's habits.

PMID- 16091904
TI  - Crimean-Congo hemorrhagic fever: a case of nosocomial transmission.

PMID- 16091905
TI  - Multiloculated pleural empyema following acupuncture.

PMID- 16091906
TI  - HIV genetic diversity: any implications for drug resistance?
AB  - At least nine different genetic HIV-1 subtypes and several circulating
      recombinant forms exist, which in addition to HIV-1 subgroups and HIV-2 account
      for the global AIDS pandemic. Even though HIV-1 subtype C and A predominate
      globally, antiretroviral drugs have been designed based on sequences of clade B
      reverse transcriptase (RT) and protease enzymes due to the domination of HIV-1
      subtype B in highly industrialized countries. Since there is no clarity about
      possible effects of the genetic diversity of HIV-1 on therapy outcome and drug
      resistance, multiple studies have been performed with divergent results. Up to
      now this question remains to be answered.

PMID- 16091908
TI  - [Can preoperative fine-needle aspiration of parotid tumors pose problems for a
      definitive histological diagnosis?].
AB  - INTRODUCTION: Fine-needle aspiration cytology (FNAC) is a minimally invasive
      procedure that offers high specifity and acceptable sensitivity in the
      preoperative diagnosis of parotid tumors. FNAC provides information that can be
      particularly valuable in surgical planning and patient education. In some cases,
      it may even help prevent unnecessary surgery. After an FNA procedure, on rare
      occasions, morphological changes in the tumor may be observed and can make a
      definitive histological examination difficult or even impossible. METHODS:
      Histopathological changes in parotid tumors after preoperative FNAC are described
      on the basis of a case report and a survey of the literature. RESULTS: In rare
      cases, puncture-induced histopathological changes, such as hyalinization of the
      subepithelial stroma, necrosis and squamous metaplasia, so extensive that a
      definitive histological diagnosis is difficult, are observed. In the present case
      report, fine-needle aspiration of a 3 x 2 cm tumor, which had been classified as
      malignant on the basis of cytological findings, resulted in complete necrosis and
      made a definitive histological diagnosis impossible. Similar cases have been
      described by other authors in recent years. DISCUSSION: In rare cases,
      histological changes in the tumor tissue can occur after an FNA procedure, making
      a definitive histological examination difficult or even impossible. When a
      preoperative FNAC is performed, the pathologist in charge should be advised
      accordingly. In addition, patients should be informed about this infrequent risk
      before undergoing the procedure.

PMID- 16091907
TI  - [Vocal efficiency parameters in children and adolescents: effect of physical
      development and singing activity].
AB  - The influence of physical development and singing activity on vocal efficiency in
      children and adolescents is well known from clinical experience. There is,
      however, no comparative study between singing and non-singing children which also
      considers the influence of age and gender. Therefore, standard values for
      evaluation in clinical practice are missing. We examined the following parameters
      in 164 healthy children and adolescents (90 boys, 74 girls; 11-16 years), 86
      without singing activity (group A) and 78 members of children's and youth choirs
      (group B): frequency and dynamic range of voice and its borders with a voice
      range profile, mean fundamental frequency (normal and loud phonation), maximum
      voice intensity, and maximum duration of intonation. The statistical analysis was
      performed using three-way ANOVA. We found significantly higher ranges of
      frequency and intensity in singing children and adolescents (p<0.0001). The
      borders of the dynamic range and the upper border of the frequency range were
      significantly higher in group B (p<0.0001). The boys in group B used a higher
      mean fundamental frequency during loud phonation. There were no significant
      differences between groups in maximum voice intensity (p=0.051) but a tendency
      towards higher values in singing children. As an unexpected result, we found
      significantly higher values in maximum duration of intonation in group A
      (p<0.0001) independent of age and gender, which seems to be related to the
      methods used. Regular training of the singing voice results in positive effects
      on several voice parameters in children as well as adolescents. Our results can
      be used for estimating standard values in professional clinical and educational
      care of young singing voices and non-singing children. For this purpose, voice
      range profile is particularly suitable.

PMID- 16091910
TI  - To: Hyllienmark L, Maltez J, Dandenell A, Ludvigsson J, Brismar T (2005) EEG
      abnormalities with and without relation to severe hypoglycaemia in adolescents
      with type 1 diabetes. Diabetologia 48:412-419.

PMID- 16091909
TI  - The role of total and high-molecular-weight complex of adiponectin in vascular
      function in offspring whose parents both had type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Adiponectin is an adipokine with insulin-sensitising and anti
      atherogenic properties. We studied the role played by total adiponectin and by
      the bioactive high-molecular-weight (HMW) oligomeric complexes of adiponectin in
      vascular function in offspring whose parents both had type 2 diabetes, a
      population at high risk of diabetes and atherosclerosis. METHODS: Total and %HMW
      adiponectin, the cytokines C-reactive protein, interleukin-6 and plasminogen
      activator inhibitor-1 (PAI-1), as well as lipid profiles were assayed in 19
      offspring, each with two type 2 diabetic parents. Subjects underwent OGTTs and
      IVGTTs. Endothelium-dependent vasodilation (EDV) was assessed by brachial artery
      ultrasonography. RESULTS: There was a significant relationship between %HMW and
      total adiponectin levels (r=0.72, p=0.001). Despite an expected strong positive
      correlation between HDL-cholesterol and adiponectin levels (r=0.52, p=0.04), as
      well as HDL-cholesterol and EDV (r=0.56, p<0.02), there was no significant
      relationship between either total adiponectin or % HMW adiponectin and EDV.
      Adiponectin was inversely associated with PAI-1 (r=0.50, p=0.05), but did not
      correlate with the inflammatory markers C-reactive protein or interleukin-6.
      CONCLUSIONS/INTERPRETATION: In offspring of diabetic parents, a population at
      high risk of diabetes and atherosclerotic disease, there is no relationship
      between total or %HMW adiponectin and endothelium-dependent vasodilation.
      However, low adiponectin was associated with impaired fibrinolysis as manifested
      by increased levels of plasminogen activator inhibitor-1.

PMID- 16091911
TI  - Biphasic development of an intraperitoneal rectum perforation: a rare but serious
      complication after barium enema.

PMID- 16091912
TI  - Topical 0.5% nifedipine vs. lateral internal sphincterotomy for the treatment of
      chronic anal fissure: long-term follow-up.
AB  - BACKGROUND: The aim of this study was to compare the efficacy of the local
      application of 0.5% nifedipine ointment vs. lateral internal sphincterotomy in
      the healing of chronic anal fissure. PATIENTS AND METHODS: Sixty-four patients
      with symptomatic chronic anal fissures were randomly assigned to 0.5% nifedipine
      ointment (n=32) every 8 h for 8 weeks or lateral internal sphincterotomy (n=32).
      Both groups received stool softeners and fiber supplements and were assessed at
      2, 4, 6, and 8 weeks. Long-term outcomes were determined after a median follow-up
      of 19 months (nifedipine group) and 20.5 months (lateral internal sphincterotomy
      group). RESULTS: Complete healing at 8 weeks was achieved in 30 out of 31
      patients (96.7%) in the nifedipine group and 32 out of 32 patients (100%) in the
      lateral internal sphincterotomy group (p=0.49). The overall healing rates at the
      end of follow-up were 28 out of 30 (93%) vs. 32 out of 32 (100%) in the
      nifedipine and sphincterotomy groups respectively (p=0.48). Two of the 30
      patients in the nifedipine group relapsed whereas none in the sphincterotomy
      group did. Sixteen patients (50%) developed side effects in the nifedipine group,
      compared with six patients (18.7%) in the sphincterotomy group. CONCLUSIONS:
      Topical application of 0.5% nifedipine ointment represents a new, promising,
      easily handled, effective alternative to lateral internal sphincterotomy.

PMID- 16091913
TI  - Fistula-in-ano: do antibiotics make a difference?
AB  - BACKGROUND: The objective of this study was to evaluate the hypothesis that
      antibiotics in conjunction with drainage of anorectal abscesses will reduce the
      incidence of fistulae formation. The impact of age and associated comorbidity on
      the formation of fistulae were also evaluated. METHODS: Patients with a diagnosis
      of anorectal abscesses were identified from the database of a single colorectal
      practice. Demographic data, comorbidity, antibiotic usage, and fistulae formation
      were collected from review of patient's charts and phone contact. Statistical
      analysis was performed with the two-sided Fisher's exact and Wald's chi-square
      tests. RESULTS: Fifty-six patients with complete data were analyzed. The overall
      fistulae formation rate was 32%. Of all patients, 45% received a course of broad
      spectrum antibiotics at the time of drainage and 48% of patients had associated
      comorbidity. Although trends were evident, there were no statistical significant
      associations between fistulae formation and age, comorbidity, and antibiotics.
      CONCLUSION: Although not statistically significant, there was a trend that
      antibiotics and age >45 years may be protective against the formation of
      fistulae. Similarly, the data suggest that the presence of comorbidity may
      increase the risk of fistula formation. We are encouraged by this result and
      propose to conduct a larger randomized prospective study.

PMID- 16091915
TI  - Low-dose cyclosporine A in a patient with X-linked immune dysregulation,
      polyendocrinopathy and enteropathy.

PMID- 16091914
TI  - Inherent potential for production of tumor necrosis factor-alpha by human
      intestinal macrophages.
AB  - BACKGROUND AND AIMS: Tumor necrosis factor (TNF) production by the macrophages in
      intestines appears to play a critical role in the pathogenesis of Crohn's disease
      (CD). However, it is reported that resident intestinal macrophages (both colonic
      and small-bowel) do not produce TNF after lipopolysaccharide (LPS) stimulation.
      It has not yet been proven whether or not intestinal macrophages have an inherent
      potential to produce TNF. The purpose of this study is to answer this question.
      MATERIALS AND METHODS: Colonic macrophages were isolated from lamina propria of
      human large intestine and stimulated with a variety of substances: LPS, a lipid A
      derivative (ONO-4007), killed Streptococcus bacterial body (OK-432), phorbol 12
      myristate 13-acetate, and lectins (pokeweed mitogen and Sarcophaga lectin).
      RESULTS: Colonic macrophages were phenotypically negative for CD14 and positive
      for CD68 and produced very little TNF in response to LPS, as reported previously.
      Of the substances tested, only Sarcophaga lectin, which is a defense protein of
      fleshflies (Sarcophaga peregrina), induced TNF production by the intestinal
      macrophages. In addition, when the colonic macrophages were cultured on
      immunoglobulin-A-coated dishes, their characteristic response to LPS was altered,
      and they produced TNF at a level 6.6 times higher than when on collagen-coated
      dishes. CONCLUSION: Colonic macrophages have an inherent ability to produce TNF.
      Activation of colonic macrophages by unknown substances may contribute to the
      induction of TNF production, which causes the intestinal inflammation of CD.

PMID- 16091916
TI  - Molluscum contagiosum prevents progression of staphylococcal scalded skin
      syndrome.
AB  - Prevention of progression of staphylococcal scalded skin syndrome by molluscum
      contagiosum indicated a possible interference by viral anti-cytokine molecule
      such as interleukin-18 binding protein.

PMID- 16091918
TI  - Morphological examination during in vitro cartilage formation by human
      mesenchymal stem cells.
AB  - The formation of the skeleton through endochondral ossification is one of the
      most complex processes in development. One approach to resolving this complexity
      is to examine simplified systems. In vitro cartilage formation by mesenchymal
      stem cells (MSCs) is observed when the cells are cultured as a micromass. Several
      studies have confirmed the molecular events, showing the usefulness of these
      cells as a differentiation model. We have elucidated the process of cartilage
      formation in MSCs from the morphological point of view by light and transmission
      electron microscopy and immunohistochemical examination. The morphology of the
      MSCs changed from spherical to spindle-shaped, and the cells aggregated and
      formed junctional complexes during Day 1. At Day 7, three layers were observed.
      The superficial zone consisted of several layers of elongated cells with
      junctional complexes. The middle zone was composed of apoptotic bodies, and the
      deep zone was occupied by chondrocyte-like cells excreting extracellular
      matrices. At Day 14, the middle zone had disappeared, and the chondrocyte-like
      cells in the deep zone were detected within cartilage lacuna. They were covered
      by cartilage matrices containing collagen types I, II, and X and chondroitin
      sulfate. By Day 21, the outer layer consisting of spindle-shaped cells had
      disappeared in places. As the pellet grew, the outer layer seemed to be unable to
      stretch to maintain a constant covering around the pellet. Our findings have thus
      revealed that MSCs change their morphology depending upon their microenvironment
      during differentiation. In vitro cartilage formation by MSCs makes it possible to
      clarify the detailed morphological events that occur during chondrogenesis.

PMID- 16091917
TI  - Inherited disorders of the IL-12-IFN-gamma axis in patients with disseminated BCG
      infection.
AB  - Disseminated BCG infection is a rare complication of vaccination that occurs in
      patients with impaired immunity. In recent years, a series of inherited disorders
      of the IL-12-IFN-gamma axis have been described that predispose affected
      individuals to disseminated disease caused by BCG, environmental Mycobacteria,
      and non-typhoidal Salmonella. The routine immunological work-up of these patients
      is normal and the diagnosis requires specific investigation of the IL-12-IFN
      gamma circuit. We report here the first two such patients originating from and
      living in Iran. The first child is two years old and suffers from complete IFN
      gamma receptor 2 deficiency and disseminated BCG infection. He is currently in
      clinical remission thanks to prolonged multiple antibiotic therapy. The other, a
      28-year-old adult, suffers from IL-12p40 deficiency and presented with
      disseminated BCG infection followed by recurrent episodes of systemic
      salmonellosis. He is now doing well. A third patient of Iranian descent, living
      in North America, was reported elsewhere to suffer from IL-12Rbeta1 deficiency.
      These three patients thus indicate that various inherited defects of the IL-12
      IFN-gamma circuit can be found in Iranian people. In conclusion we recommend to
      consider the disorders of the IL-12-IFN-gamma circuit in all patients with severe
      BCG infection, disseminated environmental mycobacterial disease, or systemic non
      typhoidal salmonellosis, regardless of their ethnic origin and country of
      residence.

PMID- 16091919
TI  - Paraneoplastic rheumatic syndromes.
AB  - Paraneoplastic symptoms caused by a malignancy but not directly related to tumour
      invasion are the result of a wide variety of tumour-derived biologic mediators,
      such as hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and
      paracrine mediators. Recognition of paraneoplastic syndromes is important, as it
      may lead to an early diagnosis of cancer. On the other hand, the clinical
      severity of the symptoms can be used as a guide to the extent of response to
      underlying tumour therapy. The quality of life of the patient is affected,
      therefore the palliative treatment of paraneoplasia is very important.

PMID- 16091921
TI  - [Permissive anemia in patients with acute coronary syndrome].

PMID- 16091920
TI  - Is intraarticular sodium hyaluronate injection an alternative treatment in
      patients with adhesive capsulitis?
AB  - The aim of this study was to compare the efficacy of sodium hyaluronate (SH)
      injection with the most common treatment methods, intraarticular steroid
      injection and physical therapy modalities in patients with adhesive capsulitis
      (AC). A total of 95 shoulders of 90 patients were included in the study and were
      randomized in four groups. The patients were treated with SH injection (group 1),
      triamsinolone acetonide (group 2) or physical therapy modalities (group 3). Group
      4 patients were served as controls. Pain severity, passive ranges of motion and
      functional considerations were measured before, and 15 days and 3 months after
      the treatments. In all treatment groups, there were significant improvements at
      both the 15th day and third month in all parameters (for each, p<0.001). The
      passive abduction values on the 15th day was found significantly higher in group
      3 when compared with group 1 and controls (for each, p<0.001). At the third
      month, the passive abduction values of the groups 2 and 3 were improved when
      compared with the control group (p<0.001). Constant score was higher in group 3
      on 15th day when compared with group 1. At the third month, all treatment groups
      were improved significantly compared with control group (p<0.001). We provided
      the best results in physical therapy modalities applied group for AC treatment.
      However, we think that SH injection may be administered as an alternative
      treatment method.

PMID- 16091922
TI  - [Preoperative long-term therapy].
AB  - A large number of patients undergoing elective surgical procedures already take
      routine medication preoperatively. The majority of these patients use drugs for
      therapy of preexisting cardiovascular, pulmonary or endocrinological diseases
      which are independent of the planned surgical procedure. The number and type of
      preoperative drug therapy are correlated to age, gender and co-morbidity of the
      patients. Furthermore, patients with higher ASA-classes usually take more drugs,
      as they suffer from several medical diseases. Information about the perioperative
      handling of routine drug therapy is important for the planning of anaesthesia and
      surgery. A close cooperation of all medical specialities involved is necessary,
      in particular when patients take anticoagulants or other substances which should
      be withdrawn or replaced. This review focuses on the handling of routine
      preoperative medication by the anaesthesiologist in the light of available
      literature.

PMID- 16091923
TI  - [Anaesthesiological management of mediastinal tumors].
AB  - The perioperative management of patients with mediastinal masses is a special
      clinical challenge in our field. Even though regional anaesthesia is normally the
      first choice, in some cases it is not feasible due to the method of operation. In
      these cases general anaesthesia is the second option but can lead to respiratory
      and haemodynamic decompensation due to tumor-associated compression syndrome
      (mediastinal mass syndrome). The appropriate treatment begins with the
      preoperative risk classification on the basis of clinical and radiological
      findings. In addition to anamnesis, chest radiograph, and CT, dynamical methods
      (e.g. pneumotachography and echocardiography) should be applied to verify
      possible intraoperative compression syndromes. The induction of general
      anaesthesia is to be realized in awake-fiberoptic intubation with introduction of
      the tube via nasal route while maintaining the spontaneous breathing of the
      patient. The anaesthesia continues with short effective agents applied inhalative
      or iv. If possible from the point of operation, agents of muscle relaxation are
      not to be applied. If the anaesthesia risk is classified as uncertain or unsafe,
      depending on the location of tumor compression (tracheobronchial tree, pulmonary
      artery, superior vena cava), alternative techniques of securing the respiratory
      tract (different tubes, rigid bronchoscope) and cardiopulmonary bypass with
      extracorporal oxygen supply are prepared. For patients with severe clinical
      symptoms and extensive mediastinal mass, the preoperative cannulation of femoral
      vessels is also recommended. In addition to fulfilling technical and personnel
      requirements, an interdisciplinary cooperation of participating fields is the
      most important prerequisite for the optimal treatment of patients.

PMID- 16091924
TI  - [Percutaneous dilational tracheostomy. Indications--techniques--complications].
AB  - Tracheostomy is a generally accepted procedure that assures free access to the
      airways in long-term lung ventilation. Apart from surgical tracheostomy,
      percutaneous dilational tracheostomy (PDT) has been increasingly employed in
      intensive care units. Presently, five dilatation methods are available, all
      equally allowing the performance of a secure and low-risk, bedside tracheostomy
      in the intensive care unit. Exact knowledge of the anatomy of the neck region and
      of the entire procedure are preconditions for a safe intervention. Percutaneous
      procedures offer advantages over surgical tracheostomy in terms of complications.
      To minimize the risks, expertise in airway management during PDT and knowledge of
      the particularities of cannula replacement in dilational tracheostoma, are
      compulsory. Endoscopic control assures that the tracheostoma can be placed
      correctly and that possible complications can be recognised early. The incidence
      of a serious tracheal stenosis after PDT is low.

PMID- 16091926
TI  - [Static fundus perimetry in normals. Microperimeter 1 versus SLO].
AB  - BACKGROUND: The Microperimeter 1 (MP-1) allows for fundus-controlled static
      perimetry of the central visual field. The purpose of this study was to compare
      MP-1 fundus perimetry with the already established scanning laser ophthalmoscope
      (SLO) fundus perimetry concerning detected threshold values of light increment
      sensitivity in normals. METHOD: In 31 eyes of 31 healthy volunteers a fundus
      controlled static threshold perimetry was carried out each with the MP-1 (Nidek
      Technologies) and the SLO (Rodenstock). In the central 21 degrees x 12 degrees
      visual field light increment sensitivity threshold values for 40 corresponding
      stimulus locations were compared in a rectangular 3 degree-grid. RESULTS: The
      average light increment sensitivity was 19.1+/-0.5 dB with the MP-1 and 17.2+/
      0.9 dB with the SLO. On average the threshold values of the 40 corresponding test
      locations were 1.9+/-1.3 dB higher with the MP-1 than with the SLO. CONCLUSION:
      Both the MP-1 and SLO offer the possibility of a reproducible functional analysis
      of the central retina under simultaneous fundus control. For comparison of
      results of the MP-1 and SLO fundus perimetry, a correction factor of
      approximately 2 dB should be used.

PMID- 16091927
TI  - Novel roles of aquaporins revealed by phenotype analysis of knockout mice.
AB  - The aquaporins (AQPs) are small integral membrane proteins that transport water
      and in some cases small solutes such as glycerol. Physiological roles of the ten
      or more mammalian AQPs have been proposed based on their expression in
      epithelial, endothelial and other tissues, their regulation, and in some cases
      the existence of humans with AQP mutation. Here, the role of AQPs in mammalian
      physiology is reviewed, based on phenotype analysis of transgenic mouse models of
      AQP deletion/mutation. Phenotype studies support the predicted roles of AQPs in
      kidney tubule and microvessel fluid transport for urinary concentrating function,
      and in fluid-secreting glandular epithelia. The phenotype studies have also shown
      unexpected roles of AQPs in brain and corneal swelling, in neural signal
      transduction, in regulation of intracranial and intraocular pressure, and in
      tumor angiogenesis and cell migration. The water/glycerol-transporting AQPs were
      found to play unexpected roles in skin hydration and in fat metabolism. However,
      many phenotype studies were negative, such as normal airway/lung and skeletal
      muscle function, despite AQP expression, indicating that tissue-specific AQP
      expression does not indicate physiological significance. The mouse phenotype data
      suggest that modulators of AQP expression/function may have such wide-ranging
      clinical applications as diuretics and in the treatment of brain swelling,
      glaucoma, epilepsy, obesity, and cancer.

PMID- 16091925
TI  - Gluten: a two-edged sword. Immunopathogenesis of celiac disease.
AB  - Celiac disease (CD) is a small intestinal disorder caused by adaptive and innate
      immune responses triggered by the gluten proteins present in wheat. In the
      intestine, gluten is partially degraded and modified, which results in gluten
      peptides that bind with high affinity to HLA-DQ2 or HLA-DQ8 and trigger an
      inflammatory T cell response. Simultaneously, gluten exposure leads to increased
      production of IL15, which induces the expression of NKG2D on intraepithelial
      lymphocytes and its ligand MICA on epithelial cells, leading to epithelial cell
      destruction. The gluten-specific T cell response results in the production of
      antibodies against tissue transglutaminase and these are specific indicators of
      disease. CD is one of the most common inherited diseases, the HLA-DQ locus being
      the major contributing genetic factor. However, as the inheritance does not
      follow a Mendelian segregation pattern, multiple other genes, each with relative
      weak effect, contribute to disease development. An important role for
      environmental factors, however, can not be ignored as the concordance rate in
      monozygous twins is considerably less than 100%. The identification of these
      environmental factors and susceptibility genes may allow a better understanding
      of disease etiology and provide diagnostic and prognostic markers. The current
      treatment for CD consists of a life-long gluten-free diet. Although long thought
      to be impossible, recent results suggest that the development of nontoxic wheat
      varieties may be feasible, which would aid disease prevention and provide an
      alternative food source for patients.

PMID- 16091929
TI  - Effective display of metallothionein tandem repeats on the bioadsorption of
      cadmium ion.
AB  - To increase the level of adsorption of heavy metal ions in surface-engineered
      yeasts, a yeast metallothionein (YMT) was tandemly fused and displayed by means
      of an alpha-agglutinin-based display system. The display of the YMT and its
      tandem repeats was examined by immunofluorescent labeling. The adsorption and
      recovery of Cd(2+) on the cell surface was increasingly enhanced with increasing
      number of tandem repeats. All Cd(2+)-binding sites in the YMT tandem repeats were
      suggested to be completely occupied. To investigate the relationship between cell
      surface adsorption and protection against heavy metal ion toxicity, the tolerance
      of these surface-engineered yeasts to Cd(2+) was examined by growing in Cd(2+)
      containing liquid medium. The rate of growth was found to be dependent on the
      number of displayed tandem repeats of YMT. These results suggest that the
      characteristics of surface-engineered yeasts as a bioadsorbent were dependent on
      the ability of the displayed proteins to bind metal ions, and the adsorption of
      heavy metal ions on the cell surface plays a major role in the ability of the
      cells to resist the toxic effects of metal ions.

PMID- 16091928
TI  - Microbial antibiotic production aboard the International Space Station.
AB  - Previous studies examining metabolic characteristics of bacterial cultures have
      mostly suggested that reduced gravity is advantageous for microbial growth. As a
      consequence, the question of whether space flight would similarly enhance
      secondary metabolite production was raised. Results from three prior space
      shuttle experiments indicated that antibiotic production was stimulated in space
      for two different microbial systems, albeit under suboptimal growth conditions.
      The goal of this latest experiment was to determine whether the enhanced
      productivity would also occur with better growth conditions and over longer
      durations of weightlessness. Microbial antibiotic production was examined onboard
      the International Space Station during the 72-day 8A increment. Findings of
      increased productivity of actinomycin D by Streptomyces plicatus in space
      corroborated with previous findings for the early sample points (days 8 and 12);
      however, the flight production levels were lower than the matched ground control
      samples for the remainder of the mission. The overall goal of this research
      program is to elucidate the specific mechanisms responsible for the initial
      stimulation of productivity in space and translate this knowledge into methods
      for improving efficiency of commercial production facilities on Earth.

PMID- 16091930
TI  - Bioaugmentation and enhanced formation of microbial granules used in aerobic
      wastewater treatment.
AB  - Microbial aggregates of an aerobic granular sludge can be used for the treatment
      of industrial or municipal wastewater, but their formation from a microbial
      activated sludge requires several weeks. Therefore, the aim of this research was
      the selection of microbial cultures to shorten the granule-forming period from
      several weeks to a few days. An enrichment culture with the ability to accelerate
      granulation was obtained by repeating the selection and batch cultivation of fast
      settling microbial aggregates isolated from the aerobic granular sludge.
      Bacterial cultures of Klebsiella pneumoniae strain B and Pseudomonas veronii
      strain F, with self-aggregation indexes of 65 and 51%, respectively, and a
      coaggregation index of 58%, were isolated from the enrichment culture. A mixture
      of these strains with the activated sludge was used as an inoculum in an
      experimental sequencing batch reactor to start up an aerobic granulation process.
      Aerobic granules with a mean diameter of 446+/-76 microm were formed in an
      experiment after 8 days of cultivation, but microbial granules were absent in
      controls. Considering biosafety issues, K. pneumoniae strain B was excluded from
      further studies, but P. veronii strain F was selected for larger-scale testing.

PMID- 16091931
TI  - The degradation of alpha-quaternary nonylphenol isomers by Sphingomonas sp.
      strain TTNP3 involves a type II ipso-substitution mechanism.
AB  - The degradation of radiolabeled 4(3',5'-dimethyl-3'-heptyl)-phenol [nonylphenol
      (NP)] was tested with resting cells of Sphingomonas sp. strain TTNP3.
      Concomitantly to the degradation of NP, a metabolite identified as hydroquinone
      transiently accumulated and short-chain organic acids were then produced at the
      expense of hydroquinone. Two other radiolabeled isomers of NP, 4(2',6'-dimethyl
      2'-heptyl)-phenol and 4(3',6'-dimethyl-3'-heptyl)-phenol, were synthesized. In
      parallel experiments, the 4(2',6'-dimethyl-2'-heptyl)-phenol was degraded more
      slowly than the other isomers of NP by strain TTNP3, possibly because of effects
      of the side-chain structure on the kinetics of degradation. Alkylbenzenediol and
      alkoxyphenol derivatives identified as metabolites during previous studies were
      synthesized and tested as substrates. The derivatives were not degraded, which
      indicated that the mineralization of NP does not proceed via alkoxyphenol as the
      principal intermediate. The results obtained led to the elucidation of the
      degradation pathway of NP isomers with a quaternary alpha-carbon. The proposed
      mechanism is a type II ipso substitution, leading to hydroquinone and nonanol as
      the main metabolites and to the dead-end metabolites alkylbenzenediol or
      alkoxyphenol, depending on the substitution at the alpha-carbon of the
      carbocationic intermediate formed.

PMID- 16091932
TI  - Mouse models of efficient and inefficient anti-tumor immunity, with emphasis on
      minimal residual disease and tumor escape.
AB  - Tumor escape from the host immune response remains the major problem holding the
      development of immunotherapies for cancer. In this review, congenic mouse lines
      are discussed that differ dramatically in their ability to respond to tumors
      tested and, thereby, to survive or to succumb to the tumor and/or its metastases.
      This ability is under the control of either MHC class I or nontrivial MHC class
      II beta genes expressed in a small subpopulation of antigen-presenting cells. Two
      hypotheses can explain the results obtained so far: (1) emergence of tumor cell
      variants that escape the host immune response in morbid mice but are eliminated
      in survivors, and (2) tumor-induced immunosuppression, which is either efficient
      or not, depending on the congenic line used. It is argued that further
      experimentation on these congenics will allow to choose the correct hypothesis,
      and to characterize the mechanism(s) of elimination of minimal residual disease
      and prevention of tumor escape by the immune system of survivors as well as the
      reason(s) for its failure in morbid mice. It is also argued that the use of these
      models will substantially increase the chance to resolve the controversy of poor
      correlation of immunotherapy testing in mice with clinical results.

PMID- 16091933
TI  - Tripeptide tyroserleutide enhances the antitumor effects of macrophages and
      stimulates macrophage secretion of IL-1beta, TNF-alpha, and NO in vitro.
AB  - Tyroserleutide (YSL) is a type of active, low molecular weight polypeptide,
      comprised of three amino acids, which has antitumor effects. YSL has various
      advantages over the other bioactive peptides such as its low molecular weight,
      simple construction, nonimmunogenicity, specificity, few side effects, and ease
      of synthesis. However, the biological activities contributing to it's antitumor
      effects are not yet known. We studied the effects of YSL on the in vitro
      cytotoxic activity of BALB/c mice peritoneal macrophages (PEMphi) against the
      target tumor cell lines BEL-7402 and B16-F10. We also measured the concentrations
      of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and nitric oxide
      (NO) produced by YSL-activated Mphi, and we determined the concentrations of IL
      1beta and NO secreted by YSL-activated murine macrophage RAW264.7 cells. YSL
      activated Mphi in vitro, inhibited BEL-7402 proliferation, enhanced PEMphi
      antitumor effects, and stimulated IL-1beta, TNF-alpha, and NO production by
      RAW264.7 cells. These data suggest that YSL activates the monocyte-macrophage
      system, which enhances Mphi antitumor effects against BEL-7402 and B16-F10 cells
      and stimulates the secretion by Mphi of cytotoxic effectors such as IL-1beta, TNF
      alpha, and NO.

PMID- 16091934
TI  - Effects of geometric isomerism in dinuclear antitumor platinum complexes on their
      interactions with N-acetyl-L-methionine.
AB  - In this study, the reactions of N-acetyl-L-methionine (AcMet) with [{trans
      PtCl(NH(3))(2)}(2)-mu-H(2)N(CH(2))(6)NH(2)](NO(3))(2) (BBR3005: 1,1/t,t 1) and
      its cis analog [{cis-PtCl(NH(3))(2)}(2)-mu-{H(2)N(CH(2))(6)NH(2)}]Cl(2) (1,1/c,c
      2) were analyzed to determine the rate and reaction profile of chloride
      substitution by methionine sulfur. The reactions were studied in PBS buffer at 37
      degrees C by a combination of multinuclear ((195)Pt, {(1)H-(15)N} HSQC) magnetic
      resonance (NMR) spectroscopy and electrospray ionization time of flight mass
      spectrometry (ESITOFMS). The diamine linker of the 1,1/t,t trans complex was
      released as a result of the trans influence of the coordinated sulfur atom,
      producing trans-[PtCl(AcMet)(NH(3))(2)](+) (III) and trans
      [Pt(AcMet)(2)(NH(3))(2)](2+) (IV). In contrast the cis geometry of the dinuclear
      compound maintained the diamine bridge intact and a number of novel dinuclear
      platinum compounds obtained by stepwise substitution of sulfur on both platinum
      centers were identified. These include (charges omitted for clarity): [{cis
      PtCl(NH(3))(2)}-mu-NH(2)(CH(2))(6)NH(2)-{cis-Pt(AcMet)(NH(3))(2)}] (V); [{cis
      Pt(AcMet)(NH(3))(2)}(2)-mu-NH(2)(CH(2))(6)NH(2)] (VI); [{cis-PtCl(NH(3))(2)}-mu
      NH(2)(CH(2))(6)NH(2)-{PtCl(AcMet)NH(3)] (VII); [{PtCl(AcMet)(NH(3))}(2)-mu
      NH(2)(CH(2))(6)NH(2)] (VIII); [{trans-Pt(AcMet)(2)(NH(3))}-mu
      NH(2)(CH(2))(6)NH(2)-{PtCl(AcMet)(NH(3))] (IX) and the fully substituted [{trans
      Pt(AcMet)(2)(NH(3))}(2)-mu-{NH(2)(CH(2))(6)NH(2)] (X). For both compounds the
      reactions with methionine were slower than those with glutathione (Inorg Chem
      2003, 42:5498-5506). Further, the 1,1/c,c geometry resulted in slower reaction
      than the trans isomer, because of steric hindrance of the bridge, as observed
      previously in reactions with DNA and model nucleotides.

PMID- 16091935
TI  - Biophysical studies of a ruthenium(II) polypyridyl complex binding to DNA and RNA
      prove that nucleic acid structure has significant effects on binding behaviors.
AB  - The interactions of a metal complex [Ru(phen)(2)PMIP](2+) {Ru=ruthenium,
      phen=1,10-phenanthroline, PMIP=2-(4-methylphenyl)imidazo[4,5-f]1,10
      phenanthroline} with yeast tRNA and calf thymus DNA (CT DNA) have been
      investigated comparatively by UV-vis spectroscopy, fluorescence spectroscopy,
      viscosity measurements, isothermal titration calorimetry (ITC), as well as
      equilibrium dialysis and circular dichroism (CD). Spectroscopic studies together
      with ITC and viscosity measurements indicate that both binding modes of the
      Ru(II) polypyridyl complex to yeast tRNA and CT DNA are intercalation and yeast
      tRNA binding of the complex is stronger than CT DNA binding. ITC experiments show
      that the interaction of the complex with yeast tRNA is driven by a moderately
      favorable enthalpy decrease in combination with a moderately favorable entropy
      increase, while the binding of the complex to CT DNA is driven by a large
      favorable enthalpy decrease with a less favorable entropy increase. The results
      from equilibrium dialysis and CD suggest that both interactions are
      enantioselective and the Delta enantiomer of the complex may bind more favorably
      to both yeast tRNA and CT DNA than the Lambda enantiomer does, and that the
      complex is a better candidate for an enantioselective binder to yeast tRNA than
      to CT DNA. Taken together, these results indicate that the structures of nucleic
      acids have significant effects on the binding behaviors of metal complexes.

PMID- 16091936
TI  - Structural and functional reconstruction in situ of the [CuSMoO2] active site of
      carbon monoxide dehydrogenase from the carbon monoxide oxidizing eubacterium
      Oligotropha carboxidovorans.
AB  - Carbon monoxide dehydrogenase from the bacterium Oligotropha carboxidovorans
      catalyzes the oxidation of CO to CO(2) at a unique [CuSMoO(2)] cluster. In the
      bacteria the cluster is assembled post-translational. The integration of S, and
      particularly of Cu, is rate limiting in vivo, which leads to CO dehydrogenase
      preparations containing the mature and fully functional enzyme along with forms
      of the enzyme deficient in one or both of these elements. The active sites of
      mature and immature forms of CO dehydrogenase were converted into a [MoO(3)]
      centre by treatment with potassium cyanide. We have established a method, which
      rescues 50% of the CO dehydrogenase activity by in vitro reconstitution of the
      active site through the supply of sulphide first and subsequently of Cu(I) under
      reducing conditions. Immature forms of CO dehydrogenase isolated from the
      bacterium, which were deficient in S and/or Cu at the active site, were similarly
      activated. X-ray crystallography and electron paramagnetic resonance spectroscopy
      indicated that the [CuSMoO(2)] cluster was properly reconstructed. However,
      reconstituted CO dehydrogenase contains mature along with immature forms. The
      chemical reactions of the reconstitution of CO dehydrogenase are summarized in a
      model, which assumes resulphuration of the Mo-ion at both equatorial positions at
      a 1:1 molar ratio. One equatorial Mo-S group reacts with Cu(I) in a productive
      fashion yielding a mature, functional [CuSMoO(2)] cluster. The other Mo-S group
      reacts with Cu(I), then Cu(2)S is released and an oxo group is introduced from
      water, yielding an inactive [MoO(3)] centre.

PMID- 16091937
TI  - Artificial di-iron proteins: solution characterization of four helix bundles
      containing two distinct types of inter-helical loops.
AB  - Peptide-based models have an enormous impact for the development of
      metalloprotein models, as they seem appropriate candidates to mimic both the
      structural characteristics and reactivity of the natural systems. Through the de
      novo design of four-helix bundles, we developed the DF (Due Ferri) family of
      artificial proteins, as models of di-iron and di-manganese metalloproteins. The
      goal of our research is to elucidate how the electrostatic environment, polarity
      and solvent accessibility of the metal-binding site, influence the functional
      properties of di-iron proteins. The first two subsets of the DF protein family,
      DF1 and DF2, consist of two non-covalently associated helix-loop-helix motifs,
      which bind the di-metal cofactor near the center of the structure. The DF2 subset
      was designed to improve the properties of DF1: DF2 and DF2t have several changes
      in their sequences to improve solubility and metal ion access, as well as a
      change in the loop connecting the two helices. In order to evaluate how these
      changes affect the overall structure of the model proteins, we solved the NMR
      structures of the di-Zn(II) complexes of DF2 and DF2t, and compared these
      structures with those recently obtained from X-ray crystallography. Further, we
      examined the thermodynamic consequences associated with the mutations, by
      measuring the stability of DF2t in the presence of different metal ions, and
      comparing the results with the data already obtained for DF2. Taken together,
      analysis of all the data showed the importance of the turn conformation in the
      design and stability of four-helix bundle.

PMID- 16091938
TI  - A new technique for the quantitative assessment of 8-oxoguanine in nuclear DNA as
      a marker of oxidative stress. Application to dystrophin-deficient DMD skeletal
      muscles.
AB  - This is the first report on the development of an immunohistochemical technique,
      combined with quantitative image analysis, for the assessment of oxidative stress
      quantitatively in nuclear DNA in situ, and its application to measure DNA damage
      in Duchenne muscular dystrophic (DMD) muscles. Three sequential staining
      procedures for cell nuclei, a cell marker, and a product of oxidative DNA damage,
      8-oxoguanine (8-oxoG), were performed. First, the nuclei in muscle sections were
      stained with Neutral Red followed by the capture of their images with an image
      analysis system used for absorbance measurements. Second, the same sections were
      then immunostained for laminin in basement membranes as the cell marker. Next,
      the sections were treated with 2 N HCl to remove the bound Neutral Red and to
      denature tissue DNA. Third, the sections were immunostained for 8-oxoG in DNA,
      using diaminobenzidine (DAB) to reveal the antibody complex. This was followed by
      capture of the images of the immunostained sections as previously. The
      absorbances at 451.2 nm of bound Neutral Red and DAB polymer oxides, the final
      product of 8-oxoG immunostaining, were measured in the same myonuclei in the
      sections. Analysis of these absorbances permitted indices of the 8-oxoG content,
      independent of the nuclear densities, to be determined in nuclear DNA in single
      myofibres and myosatellite cells surrounded by basement membranes. We found that
      the mean index for the myonuclei in biceps brachii muscles of 2- to 7-year-old
      patients was 14% higher than that in age-matched normal controls. This finding of
      the increased oxidative stress in the myonuclei in young DMD muscles agrees with
      the previous reports of increased oxidative stress in the cytoplasm in the DMD
      myofibres and myosatellite cells. The present technique for the quantitative
      assessment of oxidative stress in nuclear DNA in situ is applicable not only in
      biomedical research but also in the development of effective drugs for
      degenerative diseases related to oxidative stress.

PMID- 16091939
TI  - Structure and microtubule-nucleation activity of isolated Drosophila embryo
      centrosomes characterized by whole mount scanning and transmission electron
      microscopy.
AB  - Experimental approaches in Drosophila melanogaster over the last 20 years have
      played a fundamental role in elucidating the function, structure and molecular
      composition of the centrosome. However, quantitative data on the structure and
      function of the Drosophila centrosome are still lacking. This study uses, for the
      first time, whole mount electron microscopy in combination with negative staining
      on isolated centrosomes from the early Drosophila embryos to analyze its
      dimensions, structure and capacity to nucleate microtubules in vitro. We show
      that these organelles are on average 0.75 microm in diameter and have abundant
      pericentriolar material which often appears fibrillar and with bulbous
      protrusions. Corresponding to the abundant pericentriolar material, extensive
      microtubule nucleation occurs. Quantification of the number of microtubules
      nucleated showed that 50-300 active nucleation sites are present. We examined via
      electron microscopy immunogold labeling the distribution of gamma-tubulin, CNN,
      Asp and the MPM-2 epitopes that are phosphorylated through Polo and the Cdk1
      kinase. The distribution of these proteins is homogeneous, with the MPM-2
      epitopes exhibiting the highest density. In contrast, centrosomal subdomains are
      identified using a centriole marker to relate centrosome size to the centriole
      number by electron microscopy. In conclusion, we present a clear-cut technique
      assaying and quantifying the microtubule nucleation capacity and antigen
      distribution complementing molecular studies on centrosome protein complexes,
      cell organelle assembly and protein composition.

PMID- 16091940
TI  - Complications of acute fatty liver of pregnancy treated with activated protein C.
AB  - INTRODUCTION: Acute fatty liver (AFL) of pregnancy is a difficult and challenging
      diagnosis. The treatment plan is usually supportive. CASE REPORT: We present a
      case of a patient with AFL of pregnancy and Gram-negative endomyometritis and
      sepsis. Our treatment plan included the use of activated protein C (APC).
      CONCLUSION: This is the first case report of the use of APC in a post-partum
      patient with AFL and sepsis.

PMID- 16091941
TI  - Proteolytic activity of Lactobacillus delbrueckii ssp. bulgaricus and
      Streptococcus thermophilus in frozen-stored Kashkaval cheese.
AB  - Proteolytic activity of Lactobacillus delbrueckii ssp. bulgaricus and
      Streptococcus thermophilus in Kashkaval cheeses of varying aging times, stored at
      -10 to -12 degrees C for 12 months, was studied. It was established that the
      proteolysis of Kashkaval cheese induced by the starter culture was significantly
      delayed by freezing. The noncasein nitrogen (NCN/TN) and nonprotein nitrogen
      (NPN/TN) as a percentage of total nitrogen increased slightly during frozen
      storage of Kashkaval. It was found that NCN/TN and NPN/TN values increased to a
      larger extent in frozen-stored Kashkaval samples with shorter aging time.
      Enhanced proteolysis was observed during ripening of thawed Kashkaval cheese.
      There was greater accumulation of noncasein nitrogen in thawed Kashkaval samples
      compared to the control samples. The enhanced proteolysis during ripening of
      thawed Kashkaval cheese resulted in larger amounts of high and medium molecular
      weight peptides and lower amounts of low molecular weight peptides and free amino
      acids as compared to controls.

PMID- 16091942
TI  - Degradation of RNA during the autolysis of Saccharomyces cerevisiae produces
      predominantly ribonucleotides.
AB  - Autolytic degradation of yeast RNA occurs in many foods and beverages and can
      impact on the sensory quality of the product, but the resulting complex mixture
      of nucleotides, nucleosides and nucleobases has not been properly characterised.
      In this study, yeast autolysis was induced by incubating cell suspensions of
      Saccharomyces cerevisiae at 30-60 degrees C (pH 7.0), and at pH 4.0-7.0 (40
      degrees C) for 10-14 days, and the RNA degradation products formed during the
      process were determined by reversed-phase HPLC. Up to 95% of cell RNA was
      degraded, with consequent leakage into the extracellular environment of mainly 3'
      , 5'- and 2'-ribonucleotides, and lesser amounts of polynucleotides,
      ribonucleosides and nucleobases. The rate of RNA degradation and the composition
      of the breakdown products varied with temperature and pH. RNA degradation was
      fastest at 50 degrees C (pH 7.0). Autolysis at lower temperatures (30 degrees C
      and 40 degrees C) and at pH 5.0 and 6.0 favoured the formation of 3'-nucleotides,
      whereas autolysis at 40 degrees C and 50 degrees C (pH 7.0) favoured 5'- and 2'
      nucleotides. The best conditions for the formation of the two flavour-enhancing
      nucleotides, 5'-AMP and 5'-GMP, were 50 degrees C (pH 7.0) and pH 4.0 (40 degrees
      C), respectively.

PMID- 16091943
TI  - Genetic control for light-induced carotenoid production in non-phototrophic
      bacteria.
AB  - Carotenoids are naturally occurring yellow or orange pigments that serve as a
      protectant against photo-oxidative damages. Among the wide variety of producers,
      the prokaryotes generate a broad spectrum of carotenoids with diverse chemical
      structures that are expected to have a high potential in biotechnological
      applications. Bacterial carotenogenesis occurs in a constitutive or light-induced
      manner, which suggests the diversity of the regulatory mechanism. The mechanism
      for light-induced carotenoid production in non-phototrophic bacteria has been
      studied in detail in Myxococcus xanthus, a Gram-negative gliding bacterium. The
      complicated mechanism involves the activation of an extracytoplasmic function
      (ECF) sigma factor (CarQ), which leads to the sequestration of a MerR family
      transcriptional regulator (CarA) that represses the expression of the carotenoid
      biosynthesis genes in the dark. Recently, we identified another regulatory
      mechanism for light-induced carotenogenesis in Streptomyces coelicolor A3(2), a
      Gram-positive soil bacterium. In this organism, the transcription of the
      carotenoid biosynthesis gene cluster is specified by LitS, a photo-inducible ECF
      sigma factor. The evidence indicates that the photo-dependent transcription of
      litS is mediated by LitR, a MerR family transcriptional regulator. In addition,
      it is suggested that the conformational alteration of LitR upon receiving the
      illumination signal determines its binding to DNA. The carboxy-terminal domain of
      LitR contains a possible binding site for Vitamin B12, which may serve as a
      capturing apparatus for the illumination signal.

PMID- 16091944
TI  - Anaerobic co-reduction of chromate and nitrate by bacterial cultures of
      Staphylococcus epidermidis L-02.
AB  - Industrial wastewater is often polluted by Cr(VI) compounds, presenting a serious
      environmental problem. This study addresses the removal of toxic, mutagenic
      Cr(VI) by means of microbial reduction to Cr(III), which can then be precipitated
      as oxides or hydroxides and extracted from the aquatic system. A strain of
      Staphylococcus epidermidis L-02 was isolated from a bacterial consortium used for
      the remediation of a chromate-contaminated constructed wetland system. This
      strain reduced Cr(VI) by using pyruvate as an electron donor under anaerobic
      conditions. The aims of the present study were to investigate the specific rate
      of Cr(VI) reduction by the strain L-02, the effects of chromate and nitrate
      (available as electron acceptors) on the strain, and the interference of chromate
      and nitrate reduction processes. The presence of Cr(VI) decreased the growth rate
      of the bacterium. Chromate and nitrate reduction did not occur under sterile
      conditions but was observed during tests with the strain L-02. The presence of
      nitrate increased both the specific Cr(VI) reduction rate and the cell number.
      Under denitrifying conditions, Cr(VI) reduction was not inhibited by nitrite,
      which was produced during nitrate reduction. The average specific rate of
      chromate reduction reached 4.4 micromol Cr 10(10 )cells(-1 )h(-1), but was only
      2.0 micromol Cr 10(10 )cells(-1 )h(-1) at 20 degrees C. The maximum specific rate
      was as high as 8.8-9.8 micromol Cr 10(10 )cells(-1 )h(-1). The role of nitrate in
      chromate reduction is discussed.

PMID- 16091945
TI  - A new mass spectrometry electrospray tip obtained via precise mechanical
      micromachining.
AB  - A new electrospray tip incorporating a beveled edge has been designed for use in
      plastic electrophoresis chip/electrospray mass spectrometry. Theoretical
      hydrodynamic analysis has been conducted to model the analytical sensitivity of
      the spray tip shape. A larger sample wall, that provides increased hydraulic
      pressure, is recommended in order to preserve the fluid stability at the tip
      outlet. A polymer with better hydrophobic characteristics than glass was used for
      the spray tip in order to restrict moisture accumulation at the spray tip outlet.
      Experimental results demonstrate that the analytical sensitivity of the proposed
      scheme is better than that obtained using the flat-head tip. Although a tapered
      capillary tip is commonly used in electrophoresis chip/electrospray mass
      spectrometry, the proposed tip offers a similar sensitivity while being more
      rugged and durable than the conventional tapered capillary tip. The cost of our
      design is also much lower than conventional spray tips.

PMID- 16091946
TI  - Validated HPLC-MS-MS method for determination of azithromycin in human plasma.
AB  - A validated, highly sensitive, and selective HPLC method with MS-MS detection has
      been developed for quantitative determination of azithromycin (AZI) in human
      Na2EDTA plasma. Roxithromycin (ROX) was used as internal standard. Human plasma
      containing AZI and internal standard was ultrafiltered through Centrifree
      Micropartition devices and the concentration of AZI was determined by isocratic
      HPLC-MS-MS. Multiple reaction monitoring mode (MRM) was used for MS-MS detection.
      The calibration plot was linear in the concentration range 2.55-551.43 ng mL(-1).
      Inter-day and Intra-day precision and accuracy of the proposed method were
      characterized by R.S.D and percentage deviation, respectively; both were less
      than 8%. Limit of quantification was 2.55 ng mL(-1). The proposed method was used
      to determine the pharmacokinetic profile of AZI (250-mg tablets).

PMID- 16091947
TI  - Quantitative determination of Roundup Ready soybean (Glycine max) extracted from
      highly processed flour.
AB  - Roundup Ready soybean powder has been subjected to different amounts of DNA
      fragmentation to assess the accuracy of real-time PCR on processed food.
      Certified reference material (CRM) containing 10 g kg(-1) of Roundup Ready
      soybean (ERM-BF410d) prepared by a dry-mixing processing method was exposed to
      water at two temperatures, using three different mixing devices, or to baking
      temperature (250 degrees C) for 30 min. The amount of DNA extracted from the
      different samples was quantified by fluorimetry. The amount of fragmentation of
      the extracted DNA was characterised by gel and capillary electrophoresis and the
      percentage of genetically modified (GM) soybean was determined by a double
      quantitative real-time PCR method. Measurement of the event GTS 40-3-2 (RUR) was
      possible in all the treated materials, because small amplicons were amplified.
      Correct RUR percentages could be measured for intact powders with little or no
      DNA fragmentation. For samples with a high level of DNA degradation, however, the
      accuracy of the measurement was found to depend on the method used for DNA
      extraction. Genomic DNA isolated by use of silica resin resulted in statistically
      significant overestimation of the amount of GM.

PMID- 16091948
TI  - CT dose reduction in children.
AB  - World wide, the number of CT studies in children and the radiation exposure by CT
      increases. The same energy dose has a greater biological impact in children than
      in adults, and scan parameters have to be adapted to the smaller diameter of the
      juvenile body. Based on seven rules, a practical approach to paediatric CT is
      shown: Justification and patient preparation are important steps before scanning,
      and they differ from the preparation of adult patients. The subsequent choice of
      scan parameters aims at obtaining the minimal signal-to-noise ratio and volume
      coverage needed in a specific medical situation; exposure can be divided in two
      aspects: the CT dose index determining energy deposition per rotation and the
      dose-length product (DLP) determining the volume dose. DLP closely parallels the
      effective dose, the best parameter of the biological impact. Modern scanners
      offer dose modulation to locally minimise exposure while maintaining image
      quality. Beyond the selection of the physical parameters, the dose can be kept
      low by scanning the minimal length of the body and by avoiding any non-qualified
      repeated scanning of parts of the body. Following these rules, paediatric CT
      examinations of good quality can be obtained at a reasonable cost of radiation
      exposure.

PMID- 16091949
TI  - Casting versus surgical fixation for grade IIIA open tibial diaphysial fractures
      in children: effect on the rate of infection and the need for secondary surgical
      procedures to promote bone union.
AB  - We evaluated 39 grade IIIA open tibial fractures presenting in children younger
      than 13 years of age, to determine if the mode of fracture stabilization (casting
      vs. surgical fixation) was related to the rate of infection or the need for
      secondary surgical procedures to promote bone union. All fractures had wound
      debridement in the operating room. Thirty patients had manipulation and casting,
      and nine surgical internal or external fixation. There were two cases of
      infection in the cast-treated group and two in the surgical fixation group
      (P=0.17). None of the fractures required a secondary surgical procedure to
      promote bone union. Three of the fractures treated by manipulation and casting
      displaced; two required re-manipulation and casting and one was converted to
      external fixation. In two cases the applied external fixator had to be re
      aligned. Our results suggest that manipulation and casting is a reliable
      treatment for open tibial fractures in children.

PMID- 16091950
TI  - Knee flexion deformity from poliomyelitis treated by supracondylar femoral
      extension osteotomy.
AB  - Between April 1979 and August 1993, we treated 39 patients (49 knees) with knee
      flexion deformity after Poliomyelitis. All were subjected to fractional hamstring
      lengthening and supracondylar femoral extension osteotomy in the same surgical
      procedure. The goal was to correct the deformity and fit the lower extremities in
      long braces to improve or promote gait. Patients' mean age was 19.5 (6.5-39)
      years and the mean knee flexion deformity was 65 degrees (24-158 degrees). The
      mean follow-up was 15.5 (11.5-25) years. Postoperatively, 22 knees had full
      extension, in 26 there was an extension lag between -1 and -10 degrees and in one
      a lag greater than 10 degrees. There were no neurovascular complications and all
      patients were fitted with long leg braces. Surgical planning is important,
      especially in severe deformities, where shortening of the femur is necessary to
      facilitate the osteotomy and relax the neurovascular structures.

PMID- 16091951
TI  - Absolute compartment pressure versus differential pressure for the diagnosis of
      compartment syndrome in tibial fractures.
AB  - We studied 39 patients with 42 diaphyseal tibial fractures in whom we suspected a
      high risk for the development of a compartment syndrome. We measured the anterior
      absolute compartment pressure (ACP) every 12 h for 72 h and also recorded the
      differential pressure (DeltaP=diastolic blood pressure-ACP). Fasciotomy of the
      extremity was only performed when the differential pressure was less than 30 mmHg
      for more than 30 min. The highest values of the ACP were recorded between 24 h
      and 36 h after admission. Three fractures had a differential pressure less than
      30 mmHg and all were treated by fasciotomy. In three fractures the ACP was equal
      to or higher than 50 mmHg, of which two had a differential pressure less than 30
      mmHg. The patients were followed up for a mean of 36 months (29-45). All
      fractures healed, and none of our patients showed any sequelae of compartment
      syndrome at their last review.

PMID- 16091952
TI  - Effects of daunorubicin, mitomycin C, azathioprine and cyclosporin A on human
      retinal pigmented epithelial, corneal endothelial and conjunctival cell lines.
AB  - BACKGROUND: We wished to investigate the toxicity of four immunosuppressant and
      antimetabolic drugs, which are known to influence postoperative wound healing, on
      three different human ocular cell lines. METHODS: Acute toxicity to cyclosporin
      A, azathioprine, mitomicyn C and daunorubicin was assessed in Chang cells by
      monitoring their uptake of propidium iodide during a 3-h period. Chronic toxicity
      was assessed by monitoring the proliferation and viability of subconfluent
      cultures of Chang cells, human corneal endothelial cells (HCECs) and retinal
      pigmented epithelial (RPE) cells after continuous exposure to the drugs for 7
      days. RESULTS: Acute toxicity testing revealed no obvious effects. However, the
      chronic toxicity tests disclosed a narrow concentration range over which cell
      proliferation decreased dramatically but calcein metabolism was sustained.
      Although the three lines reacted similarly to each agent, HCECs were the most
      vulnerable to daunorubicin and mitomycin. At a daunorubicin concentration of 0.05
      microg/ml, a 75% decrease in calcein metabolism (P < 0.001) and a > or = 95% cell
      loss (P < 0.001) were observed. At a mitomycin concentration of 0.01 mug/ml, cell
      density decreased by 61% (P < 0.001) without a change in calcein metabolism, but
      at 0.1 microg/ml, the latter parameter decreased to 12% (P = 0.00014). At this
      concentration the proliferation of Chang and RPE cells decreased by more than
      50%, whilst calcein metabolism was largely sustained. Cyclosporin inhibited cell
      proliferation moderately at lower concentrations (< 5 microg/ml; P=0.05) and
      substantially at higher ones, with a corresponding decline in calcein metabolism.
      Azathioprine induced a profound decrease in both parameters at concentrations
      above 5 microg/ml. CONCLUSION: Daunorubicin, cyclosporin and azathioprine could
      be used to inhibit excessive intraocular scarring after glaucoma and
      vitreoretinal surgery without overly reducing cell viability. The attributes of
      immunosuppressants lie in their combined antiproliferative and immunomodulatory
      effects.

PMID- 16091953
TI  - Tubular carcinoma of the breast and associated intra-epithelial lesions: a
      comparative study with invasive low-grade ductal carcinomas.
AB  - Ductal intra-epithelial lesions of the breast are associated with invasive
      neoplasms and comprise a large spectrum of histological patterns. We have
      examined 23 cases of pure tubular carcinomas (TCs) of the breast and 53 cases of
      invasive ductal low-grade carcinomas to determine the relationship and
      distribution of intra-epithelial lesions, mainly of ductal in situ carcinoma
      type, but including also lobular intra-epithelial neoplasia (LIN) in both
      entities. Eleven cases of TC showed flat epithelial atypia (FEA) (47.8%), and, in
      14 and 6 cases, micropapillary and cribriform low-grade ductal carcinoma in situ
      (DCIS) were present (60.7 and 26.1%, respectively). On the opposite, in ductal
      grade I invasive carcinomas, the most frequent architectural pattern was low
      grade DCIS growing in arcades in 26 cases (49%). While absent in TCs, low-grade
      DCIS of solid type was found in five (9.4%) cases of ductal invasive carcinomas,
      where FEA were present in seven (13.2%) cases. LIN lesions were present in four
      (17.4%) cases of TC, whereas they represented 7.5%, as reported by Carstens et
      al. (Am J Clin Pathol 58:231-238, 1972), of cases of low-grade carcinomas. These
      results suggest that invasive pure TC and low-grade ductal carcinomas of the
      breast are different lesions, and support the fact that TC, of low
      histopathological grade, is a particular distinct tumoural entity.

PMID- 16091954
TI  - Insomnia complaints in patients evaluated for obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) and insomnia are among the most common sleep
      diagnoses encountered in the sleep clinic population, however little is known
      about potential interactions or associations between the two disorders. This
      retrospective, cross-sectional study was designed to determine the prevalence of
      insomnia complaints in patients undergoing evaluation for OSA and to ascertain
      which clinical and polysomnographic features are associated with insomnia. Of 255
      consecutive patients who underwent polysomnography for clinically suspected OSA,
      54.9% reported a complaint of insomnia: 33.4% reported difficulty initiating
      sleep, 38.8% difficulty maintaining sleep, and 31.4% early morning awakenings.
      Insomnia complaints were noted more commonly in patients without significant
      sleep-disordered breathing [apnea hypopnea index (AHI)<10; 81.5%] vs those with
      sleep-disordered breathing (AHI> or =10; 51.8%); p=0.01. Clinical factors
      associated with insomnia included female gender, psychiatric diagnoses, chronic
      pain, the absence of regular alcohol use, restless leg symptoms, and reports of
      nocturnal kicking. Polysomnographic factors associated with insomnia included
      lower AHI and lower desaturation index (DI). In the subgroup of patients with
      significant sleep-disordered breathing (AHI> or =10, n=228), there was no
      association between insomnia complaints and AHI or DI. These results suggest that
      insomnia is a common complaint in patients being evaluated for OSA, but it is not
      strongly associated with sleep-disordered breathing and may instead reflect other
      coexisting factors.

PMID- 16091955
TI  - Obstructive sleep apnea and ischemic heart disease in southwestern US veterans:
      implications for clinical practice.
AB  - This study describes associations between obstructive sleep apnea (OSA), intake
      of food rich in antioxidant nutrients, and ischemic heart disease (IHD) in
      military veterans. Subjects were male veterans (n=211), 54 to 85 years of age,
      and enrolled in primary care clinics at the Southern Arizona Veterans Affairs
      Health Care System (SAVAHCS), Tucson, AZ. Measures included the SAVAHCS Minority
      Vascular Center Questionnaire, the Sleep Heart Health Study Sleep Habits
      Questionnaire, the Arizona Food Frequency Questionnaire, height, weight, and
      blood pressure. Veterans with OSA were significantly more likely to be obese, to
      have elevated systolic blood pressure and physician-diagnosed IHD, more likely to
      undergo coronary angiography, and less likely to consume foods rich in
      cardioprotective antioxidants compared to veterans without OSA. After adjusting
      for confounding variables, the association between OSA and IHD remains
      significant [adjusted OR=2.99, confidence interval (CI)=1.07-8.42]. These data
      reinforce the importance of recognizing OSA within the veterans affairs health
      care system and suggest that early detection of OSA may improve veterans' health
      and well-being and reduce associated medical costs.

PMID- 16091956
TI  - CL 316,243, a selective beta3-adrenergic agonist, inhibits protein breakdown in
      rat skeletal muscle.
AB  - The in vitro effect of CL 316,243 (CL), a selective beta3-adrenoceptor agonist in
      the rate of overall proteolysis, the activity of proteolytic systems (lysosomal,
      Ca2+-dependent, ATP-dependent, and ATP-independent) and in the process of protein
      synthesis was investigated in rat skeletal muscles. The rate of overall
      proteolysis in soleus muscle from rats incubated with CL (10(-4) and 10(-5) M) or
      epinephrine (10(-5) M) was significantly decreased. In vitro rates of maximal
      activity of Ca2+-dependent proteolysis in soleus muscles were decreased by about
      41% in the presence of 10(-5) M CL. No change was observed in the activities of
      the lysosomal, ATP-dependent or ATP-independent proteolytic systems. The anti
      proteolytic effect of CL or epinephrine was partially prevented by 10(-5) M SR
      59230A, a selective beta3-adrenoceptor antagonist. The increase of proteolysis
      induced by food deprivation in soleus was abolished by in vitro addition of 10(
      5) M CL. No change in proteolysis was observed in extensor digitorum longus (EDL)
      muscles incubated with any concentration of the beta3-adrenoceptor agonist
      tested. Rates of protein synthesis were not affected by 10(-4) M CL neither in
      soleus nor EDL. The data suggest that a beta3-adrenoceptor-mediated inhibition of
      Ca2+-dependent proteolysis participates of the antiproteolytic effect of
      catecholamines in oxidative muscles.

PMID- 16091957
TI  - Divalent metal-ion transporter DMT1 mediates both H+ -coupled Fe2+ transport and
      uncoupled fluxes.
AB  - The H(+) -coupled divalent metal-ion transporter DMT1 serves as both the primary
      entry point for iron into the body (intestinal brush-border uptake) and the route
      by which transferrin-associated iron is mobilized from endosomes to cytosol in
      erythroid precursors and other cells. Elucidating the molecular mechanisms of
      DMT1 will therefore increase our understanding of iron metabolism and the
      etiology of iron overload disorders. We expressed wild type and mutant DMT1 in
      Xenopus oocytes and monitored metal-ion uptake, currents and intracellular pH.
      DMT1 was activated in the presence of an inwardly directed H(+) electrochemical
      gradient. At low extracellular pH (pH(o)), H(+) binding preceded binding of
      Fe(2+) and its simultaneous translocation. However, DMT1 did not behave like a
      typical ion-coupled transporter at higher pH(o), and at pH(o) 7.4 we observed
      Fe(2+) transport that was not associated with H(+) influx. His(272) --> Ala
      substitution uncoupled the Fe(2+) and H(+) fluxes. At low pH(o), H272A mediated
      H(+) uniport that was inhibited by Fe(2+). Meanwhile H272A-mediated Fe(2+)
      transport was independent of pH(o). Our data indicate (i) that H(+) coupling in
      DMT1 serves to increase affinity for Fe(2+) and provide a thermodynamic driving
      force for Fe(2+) transport and (ii) that His-272 is critical in transducing the
      effects of H(+) coupling. Notably, our data also indicate that DMT1 can mediate
      facilitative Fe(2+) transport in the absence of a H(+) gradient. Since plasma
      membrane expression of DMT1 is upregulated in liver of hemochromatosis patients,
      this H(+) -uncoupled facilitative Fe(2+) transport via DMT1 can account for the
      uptake of nontransferrin-bound plasma iron characteristic of iron overload
      disorders.

PMID- 16091958
TI  - The behaviour of satellite cells in response to exercise: what have we learned
      from human studies?
AB  - Understanding the complex role played by satellite cells in the adaptive response
      to exercise in human skeletal muscle has just begun. The development of reliable
      markers for the identification of satellite cell status
      (quiescence/activation/proliferation) is an important step towards the
      understanding of satellite cell behaviour in exercised human muscles. It is
      hypothesised currently that exercise in humans can induce (1) the activation of
      satellite cells without proliferation, (2) proliferation and withdrawal from
      differentiation, (3) proliferation and differentiation to provide myonuclei and
      (4) proliferation and differentiation to generate new muscle fibres or to repair
      segmental fibre injuries. In humans, the satellite cell pool can increase as
      early as 4 days following a single bout of exercise and is maintained at higher
      level following several weeks of training. Cessation of training is associated
      with a gradual reduction of the previously enhanced satellite cell pool. In the
      elderly, training counteracts the normal decline in satellite cell number seen
      with ageing. When the transcriptional activity of existing myonuclei reaches its
      maximum, daughter cells generated by satellite cell proliferation are involved in
      protein synthesis by enhancing the number of nuclear domains. Clearly,
      delineating the events and the mechanisms behind the activation of satellite
      cells both under physiological and pathological conditions in human skeletal
      muscles remains an important challenge.

PMID- 16091959
TI  - Sequential gene deletions in Hypocrea jecorina using a single blaster cassette.
AB  - In Hypocrea jecorina (anamorph: Trichoderma reesei) multiple gene deletions are
      limited by the number of readily available selection markers. We have therefore
      constructed a blaster cassette which enables successive gene knock-outs in H.
      jecorina. This 3.5 kb pyr4 blaster cassette contains the H. jecorina pyr4 marker
      gene encoding orotidine-5'-monophosphate (OMP) decarboxylase flanked by two
      direct repeats of the Streptoalloteichus hindustanus bleomycin gene (Sh ble),
      which facilitate the excision of the blaster cassette by homologous recombination
      after each round of deletion. Functionality of this pyr4 blaster cassette was
      demonstrated by deletion of the glk1 encoding glucokinase and hxk1 encoding
      hexokinase. 1.4-1.8 kb of the non-coding flanking regions of both target genes
      were cloned into the respective blaster cassettes and transformation of a pyr4
      negative H. jecorina strain with the two cassettes resulted in 10-13% of the
      transformants in the deletion of one of the two kinase genes. For excision of the
      pyr4 blaster cassettes, Deltaglk1 strains were selected for growth in the
      presence of 5-fluoroorotic acid. Recombination between the two Sh ble elements
      resulted in uridine auxotrophic strains which retained their respective
      glucokinase negative phenotype. Subsequent transformation of one of these
      auxotrophic Deltaglk1 strains with the hexokinase blaster cassette resulted in
      pyr4 prototrophic strains deleted in both glk1 and hxk1. Deltaglk1 strains showed
      reduced growth on d-glucose and d-fructose whereas Deltahxkl strains showed
      reduced compact growth on d-glucose but were unable to grow on d-fructose as
      carbon source. The double Deltaglk1Deltahxk1 deletion strain was completely
      unable to grow on either d-glucose or d-fructose.

PMID- 16091960
TI  - Debaryomyces hansenii, a highly osmo-tolerant and halo-tolerant yeast, maintains
      activated Dhog1p in the cytoplasm during its growth under severe osmotic stress.
AB  - The HOG pathway is an important mitogen-activated protein kinase (MAPK) signal
      transduction pathway in Saccharomyces cerevisiae that mediates adaptation of
      cells to hyper-osmotic stress. Activation of this pathway causes rapid but
      transient, phosphorylation of the MAPK Hog1p. Phosphorylated Hog1p is rapidly
      transported to the nucleus that results in the transcription of target genes. The
      HOG pathway appears to be ubiquitous in yeast. Components of HOG pathway have
      also been identified in Debaryomyces hansenii, a highly osmotolerant and
      halotolerant yeast. We have studied activation of HOG pathway in D. hansenii
      under different stress conditions. Our experiments demonstrated that the pathway
      is activated by high osmolarity, oxidative and UV stress but not by heat stress.
      We have provided evidence, for the first time, that D. hansenii maintains
      phosphorylated Dhog1p in the cytoplasm during its growth under severe osmotic
      stress.

PMID- 16091961
TI  - [Metallurgical differentiation of cobalt-chromium alloys for implants].
AB  - BACKGROUND: Cobalt Chromium alloys are used in cemented total hip or knee
      arthroplasty as well as in metal-on-metal bearings in total hip arthroplasty. An
      increasing number of publications report about (allergic) reactions to wear
      particles of Cobalt Chromium alloys. Reactions to nickel are more frequent in
      comparison to Cobalt or Chromium particles. It is well known that different kinds
      of Cobalt Chromium alloys contain different amounts of alloying elements;
      nevertheless. The aim of the current work was to compare the different Cobalt
      Chromium alloys according to ASTM F or ISO standards in respect to the different
      alloying elements. MATERIAL AND METHODS: Co28Cr6Mo casting alloys according to
      ASTM F 75 or ISO 5832-4 as well as forging alloy types according to ASTM F 799
      and ISO 5832 such as Co20Cr15W10Ni, Co35Ni20Cr, Fe40Co20Cr10Ni, Co20Cr20Ni, and
      Co28Cr6Mo were analyzed in respect to their element content of Co, Cr, Ni, Mo,
      Fe, W, and Mn. RESULTS: In 1935 the Cobalt based alloy "Vitallium" Co30Cr5Mo
      basically used in the aircraft industry was introduced into medicine. The
      chemical composition of this alloy based on Cobalt showed 30 wt.% Chromium and 5
      wt.% Molybdenum. The differentiation using alloy names showed no Nickel
      information in single alloy names. CONCLUSION: The information given about
      different alloys can lead to an unprecise evaluation of histopathological
      findings in respect to alloys or alloying constituents. Therefore, implant
      manufacturers should give the exact information about the alloys used and adhere
      to European law, Euronorm 93/42/EWG.

PMID- 16091962
TI  - Gene structure of the ciliate Sterkiella histriomuscorum based on a combined
      analysis of DNA and cDNA sequences from 21 macronuclear chromosomes.
AB  - Macronuclear deoxyribonucleic acid (DNA) in hypotrichous ciliates consists of a
      set of linear molecules ranging in size from 0.5 to several tens of kilobases and
      typically carrying a single gene. Each minichromosome is present at a ploidy of
      >or=1,000 per macronucleus. These molecules are known as gene-sized molecules.
      Multigene molecules are also present, but are still poorly described. In
      analyzing the encystment-excystment cycle of Sterkiella histriomuscorum, we have
      characterized a set of 21 macronuclear molecules both at the DNA and
      complementary DNA (cDNA) levels. On a total of 23 validated coding sequences, we
      mapped the 5' and 3' untranslated regions for a subset of 10 and 18 transcripts,
      respectively. A combination of DNA and cDNA data allows us to precisely determine
      several structural features of macronuclear chromosomes, such as the organization
      of multigene molecules, an intron content higher than expected, and a conserved
      sequence surrounding the initiation transcription site. It also reveals one
      coding sequence containing a transcribed 10-bp element that displays the
      characteristic features of internal eliminated sequences (IES). Its presence in a
      fraction of the minichromosomes carrying this gene raises the possibility of an
      incomplete IES excision process during the development of the S. histriomuscorum
      macronucleus.

PMID- 16091963
TI  - Dynamic contrast-enhanced perfusion MR imaging of diseased vertebrae: analysis of
      three parameters and the distribution of the time-intensity curve patterns.
AB  - OBJECTIVE: To assess the diagnostic value of perfusion MR imaging of diseased
      vertebrae by analysis of three parameters and the distribution of the time
      intensity curve (TIC) patterns. DESIGN AND PATIENTS: Dynamic MR imaging was
      performed on 34 patients with 48 lesions. All lesions were assigned to one of
      four groups: osteoporotic compression fracture, benign lesion without compression
      fracture, pathologic compression fracture, or metastatic lesion without fracture.
      Peak enhancement, steepest slope, and slope value were calculated from the TIC of
      diseased vertebrae. TICs were classified into five types. Comparisons were made
      among groups by analysis of the three parameters and the distributions of the
      TICs pattern. RESULT: All parameters of pathologic compression fracture were
      significantly higher than those of osteoporotic compression fracture (P<0.05).
      The steepest slopes of metastatic lesions with and without pathologic compression
      fracture were significantly higher than those of benign lesions without
      compression fracture (P<0.05). No characteristic distribution of the TIC pattern
      helpful for the differentiation of benign and metastatic lesions was found.
      CONCLUSION: In distinguishing osteoporotic from pathologic compression fractures,
      semiquantitative analysis of the perfusion MR imaging may be useful. However, the
      analysis of the TIC patterns can not significantly contribute to the differential
      diagnosis.

PMID- 16091964
TI  - Neuronavigational neuroendoscopic surgery. Frameless free-hand maneuvering of a
      handy rigid-rod neuroendoscope on visualized three-dimensional computerized image
      guidance: trajectory to the prepontine cistern in cadaver study.
AB  - BACKGROUND: Considering the separate benefits of neuronavigation and
      neuroendoscopy, neuroendoscopic surgery with the aid of neuronavigation systems
      will play an increasingly important role in the future. Bearing this in mind, the
      present research project was conducted to facilitate neuronavigational
      neuroendoscopic surgery along the pathway to the prepontine cistern using cadaver
      heads. MATERIALS AND METHODS: A computer-aided, frameless image-guided
      stereotactic navigation system and a new type of handy rigid-rod neuroendoscope
      were used. The ideal entry point and the safest trajectory to the prepontine
      cistern through the foramen of Monro were defined in two formalin-fixed cadaver
      heads and clinical brain MRI data. Then, maneuvering of the neuroendoscope with
      the aid of the neuronavigation system was performed. RESULTS: Straight
      trajectories from the entry point to the prepontine cistern could be designed.
      For the registration accuracy of the tip of the neuroendoscope, the virtual image
      registered a mean error distance of 5.42 mm away from the reference point along
      the axis of vertical line. However, free-hand maneuvering enabled the
      neuroendoscope to be finely manipulated without damaging brain tissues.
      Neuroendoscopic anatomical views of the interpeduncular and prepontine cistern
      were also acquired. CONCLUSION: Interactive use of free-hand maneuvering of the
      handy rigid-rod neuroendoscope together with frameless neuronavigation systems
      plot the way to true neuronavigational neuroendoscopic surgery in a safe and
      reliable manner. This pairing of the most recent technological neurosurgical
      options with better understanding of neuroendoscopic anatomy enables the
      neurosurgeon to acquire broader treatment options for central nervous system
      diseases.

PMID- 16091965
TI  - Inspiratory vs. expiratory pressure-volume curves to set end-expiratory pressure
      in acute lung injury.
AB  - OBJECTIVE: To study the effects of two levels of positive end-expiratory pressure
      (PEEP), 2 cm H(2)O above the lower inflection point of the inspiratory limb and
      equal to the point of maximum curvature on the expiratory limb of the pressure
      volume curve, in gas exchange, respiratory mechanics, and lung aeration. DESIGN
      AND SETTING: Prospective clinical study in the intensive care unit and computed
      tomography ward of a university hospital. PATIENTS: Eight patients with early
      acute lung injury. INTERVENTIONS: Both limbs of the static pressure-volume curve
      were traced and inflection points calculated using a sigmoid model. During
      ventilation with a tidal volume of 6 ml/kg we sequentially applied a PEEP 2 cm
      H(2)O above the inspiratory lower inflection point (15.5+/-3.1 cm H(2)O) and a
      PEEP equal to the expiratory point of maximum curvature (23.5+/-4.1 cmH(2)O).
      MEASUREMENTS AND RESULTS: Arterial blood gases, respiratory system compliance and
      resistance and changes in lung aeration (measured on three computed tomography
      slices during end-expiratory and end-inspiratory pauses) were measured at each
      PEEP level. PEEP according to the expiratory point of maximum curvature was
      related to an improvement in oxygenation, increase in normally aerated, decrease
      in nonaerated lung volumes, and greater alveolar stability. There was also an
      increase in PaCO(2), airway pressures, and hyperaerated lung volume. CONCLUSIONS:
      High PEEP levels according to the point of maximum curvature of the deflation
      limb of the pressure-volume curve have both benefits and drawbacks.

PMID- 16091966
TI  - Primary stability of anterior lumbar stabilization: interdependence of implant
      type and endplate retention or removal.
AB  - This is a comparative in vitro biomechanical study of the primary stability of an
      anterior lumbar interbody stabilization. The objective was to compare the
      stability of a interbody stabilizing titanium cage with and without the retention
      of the bordering vertebral endplates, as well as to compare the titanium cage
      with a tricalcium phosphate block when the endplates are removed. An adequate
      blood supply is critical for interbody fusion, which suggests surgical treatment
      of the bordering endplates. On the other hand, primary stability is improved by
      the retention of the endplates. Furthermore, bone substitute materials are
      finding more frequent use due to complications associated with autologous bone
      grafts. Ten bovine lumbar spine motion segments (average age 6 months) were
      investigated. Pure bending loadings as well as eccentric axial compression
      loadings were applied. A titanium cage and tricalcium phosphate block, were
      tested in conjunction with an anterior augmentation (MACS). Range of motion,
      neutral zone (NZ) and bending stiffness were measured under pure bending to 10
      Nm, and bending stiffness under axial loads of up to 1,500 N. Range of motion of
      both implants in flexion-extension was significantly smaller than physiologic
      (cage without endplates 4.3 degrees , cage with 2.8 degrees , block without 3.4
      degrees , and physiologic 6.6 degrees , all p<0.001). The cage with endplates and
      the block without endplates were both significantly stiffer than physiologic in
      all directions except left lateral bending. The block without endplates and the
      cage with endplates were both stiffer than the cage without endplates. The
      results suggest that the use of the bone substitute block provides better
      stability than the cage when the endplates are removed.

PMID- 16091968
TI  - Audiotactile interactions in near and far space.
AB  - In this study we investigated audiotactile spatial interactions in the region
      behind the head. In experiment 1, participants made unspeeded temporal order
      judgments (TOJs) regarding pairs of auditory and tactile stimuli presented at
      varying stimulus onset asynchronies (SOAs) using the method of constant stimuli.
      Electrocutaneous stimuli were presented to the left or right earlobe while
      auditory stimuli were presented from just behind the participant's head on either
      the same or opposite side. Participants responded significantly more accurately
      when the stimuli were presented from different sides rather than from the same
      side. In experiment 2, we used a distractor interference task to show that
      speeded left/right discrimination responses to electrocutaneous targets were also
      modulated by the spatial congruency of auditory distractors presented behind the
      head. Performance was worse (i.e. response latencies were slower and error rates
      higher) when the auditory distractors were presented on the opposite side to the
      electrocutaneous target than when they were presented on the same side. This
      crossmodal distractor interference effect was larger when white noise distractors
      were presented from close to the head (20 cm) than when they were presented far
      from the head (70 cm). By contrast, pure tone distractors elicited a smaller
      crossmodal distractor interference effect overall, and showed no modulation as a
      function of distance. Taken together, these results suggest that the spatial
      modulation of audiotactile interactions occurs predominantly for complex auditory
      stimuli (for example, white noise) originating from the region close to the back
      of the head.

PMID- 16091969
TI  - Succession after stand replacing disturbances by fire, wind throw, and insects in
      the dark Taiga of Central Siberia.
AB  - The dark taiga of Siberia is a boreal vegetation dominated by Picea obovata,
      Abies sibirica, and Pinus sibirica during the late succession. This paper
      investigates the population and age structure of 18 stands representing different
      stages after fire, wind throw, and insect damage. To our knowledge, this is the
      first time that the forest dynamics of the Siberian dark taiga is described
      quantitatively in terms of succession, and age after disturbance, stand density,
      and basal area. The basis for the curve-linear age/diameter relation of trees is
      being analyzed. (1) After a stand-replacing fire Betula dominates (4,000 trees)
      for about 70 years. Although tree density of Betula decreases rapidly, basal area
      (BA) reached >30 m2/ha after 40 years. (2) After fire, Abies, Picea, and Pinus
      establish at the same time as Betula, but grow slower, continue to gain height
      and eventually replace Betula. Abies has the highest seedling number (about 1,000
      trees/ha) and the highest mortality. Picea establishes with 100-400 trees/ha, it
      has less mortality, but reached the highest age (>350 years, DBH 51 cm). Picea is
      the most important indicator for successional age after disturbance. Pinus
      sibirica is an accompanying species. The widely distributed "mixed boreal forest"
      is a stage about 120 years after fire reaching a BA of >40 m2/ha. (3) Wind throw
      and insect damage occur in old conifer stands. Betula does not establish. Abies
      initially dominates (2,000-6,000 trees/ha), but Picea becomes dominant after 150
      200 years since Abies is shorter lived. (4) Without disturbance the forest
      develops into a pure coniferous canopy (BA 40-50 m2/ha) with a self-regenerating
      density of 1,000 coniferous canopy trees/ha. There is no collapse of old-growth
      stands. The dark taiga may serve as an example in which a limited set to tree
      species may gain dominance under certain disturbance conditions without ever
      getting monotypic.

PMID- 16091970
TI  - Climatic influences on net ecosystem CO2 exchange during the transition from
      wintertime carbon source to springtime carbon sink in a high-elevation, subalpine
      forest.
AB  - The transition between wintertime net carbon loss and springtime net carbon
      assimilation has an important role in controlling the annual rate of carbon
      uptake in coniferous forest ecosystems. We studied the contributions of
      springtime carbon assimilation to the total annual rate of carbon uptake and the
      processes involved in the winter-to-spring transition across a range of scales
      from ecosystem CO2 fluxes to chloroplast photochemistry in a coniferous,
      subalpine forest. We observed numerous initiations and reversals in the recovery
      of photosynthetic CO2 uptake during the initial phase of springtime recovery in
      response to the passage of alternating warm- and cold-weather systems. Full
      recovery of ecosystem carbon uptake, whereby the 24-h cumulative sum of NEE
      (NEEdaily) was consistently negative, did not occur until 3-4 weeks after the
      first signs of photosynthetic recovery. A key event that preceded full recovery
      was the occurrence of isothermality in the vertical profile of snow temperature
      across the snow pack; thus, providing consistent daytime percolation of melted
      snow water through the snow pack. Interannual variation in the cumulative annual
      NEE (NEEannual) was mostly explained by variation in NEE during the snow-melt
      period (NEEsnow-melt), not variation in NEE during the snow-free part of the
      growing season (NEEsnow-free). NEEsnow-melt was highest in those years when the
      snow melt occurred later in the spring, leading us to conclude that in this
      ecosystem, years with earlier springs are characterized by lower rates of
      NEEannual, a conclusion that contrasts with those from past studies in deciduous
      forest ecosystems. Using studies on isolated branches we showed that the recovery
      of photosynthesis occurred through a series of coordinated physiological and
      biochemical events. Increasing air temperatures initiated recovery through the
      upregulation of PSII electron transport caused in part by disengagement of
      thermal energy dissipation by the carotenoid, zeaxanthin. The availability of
      liquid water permitted a slightly slower recovery phase involving increased
      stomatal conductance. The most rate-limiting step in the recovery process was an
      increase in the capacity for the needles to use intercellular CO2, presumably due
      to slow recovery of Rubisco activity. Interspecific differences were observed in
      the timing of photosynthetic recovery for the dominant tree species. The results
      of our study provide (1) a context for springtime CO2 uptake within the broader
      perspective of the annual carbon budget in this subalpine forest, and (2) a
      mechanistic explanation across a range of scales for the coupling between
      springtime climate and the carbon cycle of high-elevation coniferous forest
      ecosystems.

PMID- 16091971
TI  - Hydraulic redistribution in three Amazonian trees.
AB  - About half of the Amazon rainforest is subject to seasonal droughts of 3 months
      or more. Despite this drought, several studies have shown that these forests,
      under a strongly seasonal climate, do not exhibit significant water stress during
      the dry season. In addition to deep soil water uptake, another contributing
      explanation for the absence of plant water stress during drought is the process
      of hydraulic redistribution; the nocturnal transfer of water by roots from moist
      to dry regions of the soil profile. Here, we present data on patterns of soil
      moisture and sap flow in roots of three dimorphic-rooted species in the Tapajos
      Forest, Amazonia, which demonstrate both upward (hydraulic lift) and downward
      hydraulic redistribution. We measured sap flow in lateral and tap roots of our
      three study species over a 2-year period using the heat ratio method, a sap-flow
      technique that allows bi-directional measurement of water flow. On certain nights
      during the dry season, reverse or acropetal flow (i.e.,in the direction of the
      soil) in the lateral roots and positive or basipetal sap flow (toward the plant)
      in the tap roots of Coussarea racemosa (caferana), Manilkara huberi (macaranduba)
      and Protium robustum (breu) were observed, a pattern consistent with upward
      hydraulic redistribution (hydraulic lift). With the onset of heavy rains, this
      pattern reversed, with continuous night-time acropetal sap flow in the tap root
      and basipetal sap flow in lateral roots, indicating water movement from wet top
      soil to dry deeper soils (downward hydraulic redistribution). Both patterns were
      present in trees within a rainfall exclusion plot (Seca Floresta) and to a more
      limited extent in the control plot. Although hydraulic redistribution has
      traditionally been associated with arid or strongly seasonal environments, our
      findings now suggest that it is important in ameliorating water stress and
      improving rain infiltration in Amazonian rainforests. This has broad implications
      for understanding and modeling ecosystem process and forest function in this
      important biome.

PMID- 16091972
TI  - Arthroscopically assisted retrodrade intramedullary fixation for fractures of the
      distal femur: technique, indications and results.
AB  - The purpose of this study is to present our experience with the technique, the
      problems and the potential pitfalls of arthroscopically assisted retrograde
      femoral nailing for supracondylar femoral fractures. In a 2-year period, nine
      patients (seven women, two men, average age 72 years) with supracondylar femoral
      fractures were treated in our department with a retrograde nailing under
      arthroscopic control. The mean operative time was 63.8 min (42-84 min) and the
      mean follow up period was 34.5 months (ranged 12-52). Solid union of the fracture
      was achieved in all patients without additional intervention, in 14 weeks (range
      12-18). There was no malalignment (more than 5 degrees in any plane) or implant
      failure. In conclusion we believe that the arthroscopically assisted technique is
      a very good method to treat supracondylar fractures of the femur. It has very low
      morbidity since the knee is not opened through the operation, and the surgeon has
      the ability to inspect the joint for any additional damage. It is very helpful in
      multitrauma patients and in young patients, where the precision of the entry
      point is critical. However, we do not recommend the technique in intraarticular
      fractures because the reduction is difficult and the fixation is performed with
      safety only under direct vision.

PMID- 16091975
TI  - The tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      stimulates proliferation of immortalized human pancreatic duct epithelia through
      beta-adrenergic transactivation of EGF receptors.
AB  - PURPOSE: Pancreatic ductal adenocarcinoma is an aggressive smoking-associated
      human cancer in both men and women. The nicotine-derived 4-(methylnitrosamino)-1
      (3-pyridyl)-1-butanone (NNK) is thought to contribute to the development of these
      neoplasms in smokers through genotoxic effects. However, NNK has been recently
      identified as an agonist for both beta(1)- and beta(2)-adrenergic receptors.
      Binding of NNK to these receptors stimulates proliferation of pulmonary and
      pancreatic adenocarcinomas cells in vitro and in hamster models. The goal of this
      study was to elucidate the NNK effects on the signal transduction pathways
      downstream of both beta(1)- and beta(2)-adrenergic receptors in immortalized
      human pancreatic HPDE6-c7 cells. METHODS: The HPDE6-c7 cells are developed from
      normal pancreatic duct epithelial cells which are the putative cells of origin of
      pancreatic ductal adenocarcinoma. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazoliumbromide (MTT) cell proliferation assays, Western blot and cyclic AMP
      assays were employed to demonstrate the effects of NNK and other beta(1)- and
      beta(2)-adrenergic agonists and antagonist treatments on these cells. RESULTS:
      MTT cell proliferation assays demonstrated that NNK and the classic beta
      adrenergic agonist, isoproterenol, increased cell proliferation in HPDE6-c7
      cells. Western blot and cyclic AMP assays demonstrated that NNK treatments also
      resulted in: (1) transactivation of the epidermal growth factor receptor, EGFR,
      (2) an increase in intracellular cyclic AMP accumulation, and (3) phosphorylation
      of mitogen-activated protein kinase, Erk1/2. The proliferative response to NNK
      and isoproterenol were inhibited by the use of beta-blockers (propranolol), and
      the inhibitors of adenylyl cyclase (SQ 22536), EGFR-specific tyrosine kinase (AG
      1478) and Erk (PD 98059). CONCLUSION: These findings suggest that the NNK 
      mediated beta-adrenergic receptor transactivation of the EGFR and phosphorylation
      of Erk1/2 in immortalized human pancreatic duct epithelial cells as a novel
      mechanism might contribute to the development of tobacco-associated pancreatic
      carcinogenesis.

PMID- 16091974
TI  - Iatrogenic carotid artery injury in neurosurgery.
AB  - Iatrogenic carotid artery injury (CAI) results from various neurosurgical
      procedures. A review of the literature was conducted to provide an update on the
      management of this potentially devastating complication. Iatrogenic CAIs are
      categorized according to each diagnostic or therapeutic procedure responsible for
      the injury, i.e., anterior cervical spine surgery, central venous
      catheterization, chemical substances, chiropractic manipulation, diagnostic
      cerebral angiography, middle-ear surgery, percutaneous procedures for trigeminal
      neuralgia, radiation therapy, skull-base surgery, tracheostomy, and
      transsphenoidal surgery. The incidence, mechanisms of injury, diagnostic imaging
      modalities, and reparative procedures are discussed for each procedure.
      Iatrogenic CAI may be more prevalent than had previously been thought, mostly
      because of a heightened awareness on the part of physicians and the earlier
      detection of asymptomatic patients owing to sophisticated and less-invasive
      imaging modalities. Prevention is the best treatment for every iatrogenic injury,
      and it is expected that further accumulation of experience with and knowledge of
      iatrogenic CAI will result in further reduction of this complication. Although
      some CAIs, such as radiation-induced carotid artery stenosis, may not be
      preventable, earlier intervention before the patient becomes symptomatic may
      favorably alter the prognosis. Following the rapid development of endovascular
      techniques in recent years, surgically inaccessible lesions can be treated in a
      more reliable and safe manner than before.

PMID- 16091976
TI  - Liver function assessment in workers exposed to vinyl chloride.
AB  - OBJECTIVE: To investigate liver function in vinyl chloride workers and assess its
      relation with current/past occupational exposure to vinyl chloride monomer (VCM).
      METHODS: A medical examination including the execution of liver function tests
      (LFTs) and liver ultrasonography was executed in a group of 757 workers with a
      long-standing service in the production of VCM/polyvinylchloride (PVC).
      Cumulative and maximum VCM exposures were calculated. History of viral hepatitis
      and alcohol intake were carefully investigated. Regression analysis explored the
      association between abnormal LFTs and a group of possible determinants (VCM
      cumulative and maximum exposure, BMI, age, history of viral hepatitis, alcohol
      and triglyceride levels). Also, synergistic effect between VCM and a history of
      hepatitis was analysed, as well as the possible association between VCM exposure
      and aspartate aminotransferase/alanine amino transferase (AST/ALT) ratio >1.
      Distribution of abnormal LFTs was also assessed in relation to the results
      provided by liver ultrasonography. RESULTS: The most frequently abnormal serum
      parameters were, in decreasing order: total cholesterol (27.3%), triglycerides
      (12.2%), total bilirubin (9.1%), gamma glutamil transpeptidase (GGT; 9.0%) and
      ALT (8.2%). The AST/ALT ratio >1 was present in 28.1% of workers. Abnormal LFTs
      were not found to be associated with current or past VCM exposure. High ALT
      resulted positively associated with BMI, AST with alcohol intake, GGT with
      alcohol intake and triglycerides. No synergistic effect on LFTs of exposure to
      VCM and a history of hepatitis was observed. The AST/ALT ratio >1 was not found
      to be associated with VCM exposure. The prevalence of abnormal LFTs was higher in
      case of liver steatosis (ALT) or periportal fibrosis (GGT), but not in case of
      pure hepatomegaly, as documented by ultrasonography. CONCLUSIONS: Liver function
      assessment only including LFTs is not able to detect VCM-induced liver damage,
      but reveals alterations due to non-occupational factors, such as dietary and/or
      metabolic disfunctions. The LFTs are however of importance to detect conditions
      that could recommend avoidance of exposure to VCM and are useful for medical
      counselling and health promotion purposes.

PMID- 16091978
TI  - The oldest tracheostoma patient alive?

PMID- 16091977
TI  - Cartilage and bone tissue engineering for reconstructive head and neck surgery.
AB  - The loss of cartilage and bone because of congential defects, trauma and after
      tumor resection is a major clinical problem in head and neck surgery. The most
      prevalent methods of tissue repair are through autologous grafting or using
      implants. Tissue engineering applies the principles of engineering and life
      sciences in order to create bioartificial cartilage and bone. Most strategies for
      cartilage tissue engineering are based on resorbable biomaterials as temporary
      scaffolds for chondrocytes or precursor cells. Clinical application of tissue
      engineered cartilage for reconstructive head and neck surgery as opposed to
      orthopedic applications has not been well established. While in orthopedic and
      trauma surgery engineered constructs or autologous chondrocytes are placed in the
      immunoprivileged region of joints, the subcutaneous transplant site in the head
      and neck can lead to strong inflammatory reactions and resorption of the
      bioartificial cartilage. Encapsulation of the engineered cartilage and modulation
      of the local immune response are potential strategies to overcome these
      limitations. In bone tissue engineering the combination of osteoconductive
      matrices, osteoinductive proteins such as bone morphogenetic proteins and
      osteogenic progenitor cells from the bone marrow or osteoblasts from bone
      biopsies offer a variety of tools for bone reconstruction in the craniofacial
      area. The utility of each technique is site dependent. Osteoconductive approaches
      are limited in that they merely create a favorable environment for bone
      formation, but do not play an active role in the recruitment of cells to the
      defect. Delivery of inductive signals from a scaffold can incite cells to migrate
      into a defect and control the progression of bone formation. Rapid osteoid matrix
      production in the defect site is best accomplished by using osteoblasts or
      progenitor cells.

PMID- 16091980
TI  - Seismic activity response as observed in mantled howlers (Alouatta palliata),
      Cuero y Salado Wildlife Refuge, Honduras.
AB  - This report documents the response of wild mantled howlers (Alouatta palliata) to
      coseismic activity (seismic activity at the time of an earthquake). During field
      work on the north coast of Honduras, data were collected on a habituated troop of
      mantled howlers as they responded to coseismic activity. The seismic event
      occurred on 13 February 2001 at 0822 hours local time with a magnitude of Richter
      scale 6.6, focus depth of approximately 15 km at a distance of 341 km from the
      epicentre to the field site, Cuero y Salado. At the field site, based upon
      Jeffreys and Bullen (1988), body waves, noted as P and S waves, arrived at 60 and
      87 s, respectively, with surface waves arriving approximately 103 s post-origin
      time of the seismic event. While there are three reports on non-human primate
      response to coseismic activity in the literature, they report on captive non
      human primates. This is the first documented response on a non-captive troop. In
      addition, this report compares the intensity measure encountered by a wild troop
      of howlers and one captive group of orangutans as set out by the Modified
      Mercalli Intensity scale. The Modified Mercalli measure of intensity is one of
      two standard measures of seismic activity and rates what a person sees and feels
      at their location (Wood and Neumann 1931; Richter 1958). Thus, arboreal nonhuman
      primates are found to respond to coseismic activity ranging from Level IV to
      Level VI as based upon the modified Mercalli intensity scale.

PMID- 16091979
TI  - Maxillary sinus atelectasis in a wild born gibbon (Hylobates moloch).
AB  - In a mixed sex sample of ten adult gibbon (Hylobates moloch) skulls, one cranium
      of a male with maxillary sinus atelectasis of the left side was identified. While
      external inspection revealed a slight drop of the left orbital floor, serial
      coronal computer tomography (CT) scans show characteristic changes of the left
      maxillary sinus and its surrounding structures. In addition to the sunken orbital
      floor, radiological features of the specimen include an inward bowing of the
      medial sinus wall, sinus opacification, and a reduction in maxillary sinus size
      to a slit-like cavity, which suggest a diagnosis of silent sinus syndrome. This
      report is the first, to our knowledge, of maxillary sinus atelectasis in a non
      human primate. This finding is valuable for the understanding of the pathogenesis
      and etiology of maxillary sinus atelectasis. At the same time, however,
      paleoanthropologists and primatologists may refer to this information when
      dealing with the interpretation of maxillary sinus pneumatization of partially
      broken archaeological and fossil skulls.

PMID- 16091981
TI  - Chimpanzees (Pan troglodytes) use markers to monitor the movement of a hidden
      item.
AB  - Four chimpanzees (Pan troglodytes) monitored the movement of hidden items in
      arrays of opaque cups. A chocolate candy was hidden in an array of four cups and
      temporarily presented paper markers indicated the location of the candy (which
      otherwise was not visible). These markers were either non-symbolic or symbolic
      (lexigram) stimuli that in other contexts acted as a label for the hidden candy,
      and the array was either rotated 180 degrees after the marker was removed or the
      array remained in the same location. For three of four chimpanzees, performance
      was better than chance in all conditions and there was no effect of the type of
      marker. These experiments indicate that chimpanzees can track the movement of a
      hidden item in an array of identical cups even when they never see the item
      itself, but only see a temporarily presented marker for the location of that
      item. However, there was no benefit to the use of symbolic as opposed to non
      symbolic stimuli in this performance.

PMID- 16091983
TI  - Detection of lymph node micrometastases and isolated tumor cells in sentinel and
      nonsentinel lymph nodes of colon cancer patients.
AB  - About 20% to 30% of colon cancer patients classified as node negative by routine
      hematoxylin-eosin (H&E) staining are found to have micrometastases (MM) or
      isolated tumor cells (ITC) in sentinel lymph nodes (SLNs) if analyzed by step
      sections and immunohistochemistry (IHC). Whether SLNs are in this respect
      representative for all lymph nodes was addressed in this study. SLNs were
      identified using the intraoperative blue dye detection technique. If all lymph
      nodes (SLNs and non-SLNs) of a patient were negative by routine H&E staining,
      they were step-sectioned and analyzed by IHC using pancytokeratin antibodies. We
      identified at least one SLN in 47 of the 55 patients (85%) and examined a median
      of 26 lymph nodes per patient (range 10-59). By routine H&E staining, 14 of the
      47 patients showed lymph node metastases (30%); the remaining 33 were classified
      as node-negative. In this group (33 patients), 1011 lymph nodes were analyzed by
      step sections and IHC: 14 of 70 SLNs. (20%) but only 37 of 941 non-SLNs (4%) had
      MM/ITC (p < 0.001). Furthermore, 13 of the 33 H&E-negative patients were found to
      have MM/ITC (39%). In 11 of the 13 patients, MM/ITC were identified in both SLNs
      and non-SLNs in 1 patient in the SLN only, and in 1 patient in a non-SLN only
      (sensitivity for the identification of MM/ITC: 92%; negative predictive value:
      95%). The SLN biopsy is a valid tool to detect, as well as exclude, the presence
      of MM/ITC in colon cancer patients. Our results may be of prognostic relevance
      and influence patient stratification for adjuvant therapy trials.

PMID- 16091984
TI  - Prospective randomized comparison between a new mattress technique and Cattell
      (duct-to-mucosa) pancreaticojejunostomy for pancreatic resection.
AB  - The majority of lethal complications after pancreatic head resection are due to
      septic complications after leakage from the pancreatojejunostomy. Especially the
      smooth pancreatic remnant is prone to develop parenchymal leaks from shear forces
      applied during tying of the sutures. We developed a new mattress technique that
      avoids such shear forces, and we compared this method to the standard Cattell
      (duct-to-mucosa) technique. A total of 113 patients undergoing standard
      pancreatic head resection were prospectively randomized to receive either the
      standard Cattell anastomosis (n = 56) or the new mattress technique (n = 57). All
      patients were evaluated for surgical and medical complications until discharge.
      Primary diagnosis and further demographic data compared well between the groups.
      The time to perform the mattress anastomosis was significantly shorter (15 vs. 22
      minutes; p < 0.0001). The incidence of complications at the pancreatojejunostomy,
      and the length of hospital stay and survival were not significantly different
      between the two groups; however, a trend toward more reoperations was noted in
      the Cattell group (10 vs. 5; p < 0.097). The new mattress technique is simple,
      and our data show that the two techniques yield similar incidences of
      complications. Therefore the mattress technique for pancreatojejunostomy seems to
      be safe and is, in our opinion, well suitable for training schedules in
      pancreatic surgery.

PMID- 16091985
TI  - Prevalence of thyroid nodules and carcinomas in patients operated on for renal
      hyperparathyroidism: experience with 339 consecutive patients and review of the
      literature.
AB  - The association between renal hyperparathyroidism (HPT) and differentiated
      thyroid carcinoma is discussed. To determine the prevalence and potential risk
      factors, we performed a retrospective analysis of our patients (1998-2004) and
      compared the data with the data from other surgical and autopsy studies. At our
      hospital, a total of 347 parathyroidectomies in 339 patients with renal HPT were
      performed. Most patients underwent preoperative ultrasound investigation of the
      thyroid gland and, if indicate, thyroid scintigraphy. Intraoperatively, both
      thyroid lobes were mobilized and palpated. Detected thyroid nodules were
      adequately resected and investigated histologically. A systematic analysis of the
      international literature was performed using the PubMed/MEDLINE system to
      identify publications on the prevalence of papillary thyroid carcinoma (PTC) in
      patients with renal HPT and in the overall population. Altogether, 133 patients
      (39.2%) underwent simultaneous thyroid surgery. The initial operation was
      hemithyroidectomy in 55 (16.2%), Dunhill operation in 36 (10.6%), unilateral
      subtotal resection in 17 (5.0%), bilateral subtotal resection in 5 (1.5%), and
      enucleation of a thyroid nodule in 18 (5.3%). A PTC was found in 8 of 339
      patients (2.4%) and a follicular thyroid carcinoma in 1. Among 311 patients with
      primary cervical operation, 6 (1.9%) had a papillary thyroid carcinoma. All
      papillary tumors were classified as pT1 with a diameter of 1 to 12 mm; three were
      bifocal, and only one patient had positive lymph nodes. None of the analyzed
      factors showed a significant correlation with the occurrence of thyroid
      carcinoma. Depending on the screening method, the prevalence of occult PTC in
      European autopsy studies ranged from 5% to 9% and was markedly higher in almost
      all studies than in the present one. The prevalence of PTC in the present study
      makes an etiologic association between renal HPT and PTC unlikely. The clinical
      significance of these tumors remains unclear because all incidental tumors were
      small. However, if easily and safely feasible, relevant thyroid nodules should be
      removed during parathyroid surgery.

PMID- 16091986
TI  - Normotensive pheochromocytoma: institutional experience.
AB  - We report an audit of nine cases of subclinical or normotensive pheochromocytoma
      managed in our department. This is the first report from India of such a series.
      During the period 1990-2003 a total of 45 patients of pheochromocytoma were
      diagnosed and managed in the Department of Endocrine Surgery, Sanjay Gandhi
      Postgraduate Institute of Medical Sciences. Among them, nine patients were
      diagnosed as having subclinical or normotensive pheochromocytoma. Inclusion
      criteria for normotensive pheochromocytoma were: no previous history of
      hypertension clinically and, in the previous treatment documents, any episode of
      symptoms suggesting high blood pressure. The demographic profile, clinical
      presentation, biochemical investigations, imaging results, surgical notes, and
      follow-up record were reviewed retrospectively. All patients had a primary
      complaint of flank/abdominal pain and were normotensive. Seven had elevated
      urinary metanephrine levels, and one patient had normal values. One patient did
      not undergo the urinary metanephrine assay. Imaging of the abdomen showed seven
      adrenal and two extra-adrenal masses (eight had computed tomography scans of the
      abdomen, and one underwent ultrasonography). After selective alpha-adrenergic
      blockade (prazosin), surgery was performed. Six patients required infusion of
      sodium nitroprusside intraoperatively. The final histopathology was
      pheochromocytoma in all patients. Metanephrine levels were normal during the
      follow-up. Normotensive pheochromocytomas are a distinct entity, and all adrenal
      incidentalomas should be investigated for catecholamine hypersecretion. We
      support the use of preoperative alpha-adrenergic blockade, and these patients
      should be treated along the same lines as hypertensive pheochromocytoma.

PMID- 16091987
TI  - Fracture of a renal artery stent due to mobile kidney.

PMID- 16091988
TI  - Sharp central venous recanalization by means of a TIPS needle.
AB  - The purpose of this study was to perform an alternative technique for
      recanalization of a chronic occlusion of the left brachiocephalic vein that could
      not be traversed with a guidewire. Restoration of a completely thrombosed left
      brachiocephalic vein was attempted in a 76-year-old male hemodialysis patient
      with massive upper inflow obstruction, massive edema of the face, neck, shoulder,
      and arm, and occlusion of the stented right brachiocephalic vein/superior vena
      cava. Vessel negotiation with several guidewires and multipurpose catheters
      proved unsuccessful. The procedure was also non-viable using a long, 21 G
      puncture needle. Puncture of the superior vena cava (SVC) at the distal
      circumference of the stent in the right brachiocephalic vein/superior vena cava,
      however, was feasible with a transjugular intrahepatic portosystemic shunt (TIPS)
      set under biplanar fluoroscopy using the distal end of the right brachiocephalic
      vein as a target, followed by balloon dilatation and partial extraction of
      thrombotic material of the left brachiocephalic vein with a wire basket. Finally,
      two overlapping stents were deployed to avoid early re-occlusion. Venography
      demonstrated complete vessel patency with free contrast media flow via the stents
      into the SVC, which was reconfirmed in follow-up examinations. Immediate clinical
      improvement was observed. Venous vascular recanalization of chronic venous
      occlusion by means of a TIPS needle is feasible as a last resort under certain
      precautions.

PMID- 16091989
TI  - Brachial plexus injury from CT-guided RF ablation under general anesthesia.
AB  - Brachial plexus injury in a patient under general anesthesia (GA) is not
      uncommon, despite careful positioning and, particularly, awareness of the
      possibility. The mechanism of injury is stretching and compression of the
      brachial plexus over a prolonged period. Positioning the patient within the
      computed tomography (CT) gantry for abdominal or chest procedures can simulate a
      surgical procedure, particularly when GA is used. The potential for brachial
      plexus injury is increased if the case is prolonged and the patient's arms are
      raised above the head to avoid CT image degradation from streak artifacts. We
      report a case of profound brachial plexus palsy following a CT-guided
      radiofrequency ablation procedure under GA. Fortunately, the patient recovered
      completely. We emphasize the mechanism of injury and detail measures to combat
      this problem, such that radiologists are aware of this potentially serious
      complication.

PMID- 16091990
TI  - Percutaneous drainage of 300 intraperitoneal abscesses with long-term follow-up.
AB  - The purpose of the study was to evaluate the efficacy of percutaneous drainage of
      intraperitoneal abscesses with attention to recurrence and failure rates. A
      retrospective analysis of percutaneous treatment of 300 intraperitoneal abscesses
      in 255 patients (147 male, 108 female; average age: 38 years; range: 40 days to
      90 years) for whom at least 1-year follow-up data were available was performed.
      Abscesses were drained with fluoroscopic, sonographic, or computed tomographic
      guidance. Nine abscesses were drained by simple aspiration; catheter drainage
      either by Seldinger or trocar technique was used in the remaining 291 abscesses
      with 6F to 14 F catheters. Initial cure and failure rates were 68% (203/300) and
      12% (36/300), respectively. Sixty-one abscesses (20%) were either palliated or
      temporized. The recurrence rate was 4% (12/300) and nine of them were cured by
      recatheterization, whereas three of them were treated by medication or surgery.
      The overall success and failure rates were 91% (273/300) and 9% (27/300),
      respectively, with temporized, palliated, and recatheterized recurred abscesses.
      The 30-day mortality rate was 3.1% (8/255). The mean duration of catheterization
      was 13 days. Intraperitoneal abscesses with safe access routes should be drained
      percutaneously because of high success and low morbidity, mortality, and
      recurrence rates.

PMID- 16091991
TI  - Optimal covering material for stent-grafts placed in the portal vein in a canine
      model.
AB  - PURPOSE: We evaluated the suitability of Dacron, polytetrafluoroethylene (PTFE),
      and small intestinal submucosa (SIS) as a covering material for stent-grafts
      placed in the portal vein as compared with a bare stent. METHODS: Using 24 beagle
      dogs, either bare stents or stent-grafts covered with Dacron, PTFE, or SIS were
      placed in the main trunk of the portal vein in 6 animals each. Portography was
      performed immediately after stent placement, and at 2, 4, and 12 weeks
      thereafter. Next, the extracted stents or stent-grafts were examined
      histopathologically. Neointimal thickness adjacent to the stent wire and at the
      midportion between the stent wires was compared among the groups. Then, the
      neointimal thickness at the sub- and supragraft sites was compared between each
      stent-graft group. Serial changes in the histologic features of the thickened
      neointima were also investigated. RESULTS: No significant difference was noted in
      the mean stenotic ratio of the portal vein diameter between the bare stent and
      PTFE groups, whereas it was significantly higher in the Dacron and SIS groups
      compared with the bare stent group. In neither of the studies on neointimal
      thickness adjacent to the stent wire and at the midportion between the stent
      wires were any significant differences noted between the neointimal thickness of
      the bare stent group and the sum of the neointimal thickness of the PTFE group,
      whereas the sum of the neointimal thickness of the Dacron and SIS groups was
      significantly greater than that of the bare stent group at both sites. In the
      comparison of the supragraft neointimal thickness, the SIS group showed
      significantly greater thickness than the PTFE group, while the difference between
      the Dacron and PTFE groups was not significant. In the comparison of the subgraft
      neointimal thickness, the Dacron and SIS groups showed significantly greater
      thickness than the PTFE group. CONCLUSION: The present results indicate that of
      the three covering materials examined here, PTFE is the most suitable material
      for grafts placed in the portal vein.

PMID- 16091992
TI  - Diverticula of Kommerell and aberrant subclavian arteries complicated by
      aneurysms.
AB  - This is a retrospective evaluation of the incidence of aberrant subclavian
      arteries (ASAs) and diverticula of Kommerell, as well as the occurrence and
      significance of associated aneurysms. Thoracic aortograms obtained during a 12.5
      year period were reviewed, seeking the presence of aberrant right and left
      subclavian arteries (ARSAs/ALSAs), diverticula of Kommerell, and the incidence of
      associated aortic aneurysms. Several cases were evaluated with computed
      tomography concomitantly. Results were correlated with a literature review.
      Twenty-two ASAs were identified. Nineteen were on the right (ARSAs) and three
      were on the left (ALSAs). A diverticulum of Kommerell (DOK) was also present on
      the right in seven and on the left in three. Five of these patients had
      complicating aneurysms. Four of these were associated with ARSAs and their
      diverticula. Two were atherosclerotic; one was a limited dissection and one of
      uncertain etiology was ruptured. One additional aneurysm (atherosclerotic)
      involved an ALSA/DOK. The patient with the ruptured aneurysm died in surgery;
      three were managed conservatively because of concomitant disease; and one is
      being followed because of the small size (2.5 cm) of the aneurysm. ARSAs are
      relatively uncommon and ALSAs are rare. Both ARSA and ALSA are frequently
      associated with a DOK. Aneurysms rarely involve ASAs (with or without a DOK), but
      they are associated with a high mortality rate if they are not discovered before
      rupture. Early diagnosis plus surgical and/or endovascular management can be
      lifesaving.

PMID- 16091993
TI  - Study of crystal packing on the solid-state reactivity of indomethacin with
      density functional theory.
AB  - PURPOSE: Solid-state reactions are highly anisotropic. Different polymorphs of
      the same compound may have remarkably different chemical reactivities. It was
      reported that two polymorphs of indomethacin single crystals, alpha- and gamma
      forms, reacted with ammonia gas at dramatically different rates. In this study,
      the effect of crystal packing on their difference in chemical reactivity was
      investigated by examining the electronic structures and properties of the crystal
      forms. METHODS: Ab initio methods, including density functional theory, were used
      to calculate electronic structures of the alpha- and gamma-forms of indomethacin.
      In particular, nuclear Fukui functions were obtained to elucidate how a molecule
      in a crystal may respond to an electronic perturbation that can be caused by a
      chemical reaction. RESULTS: Different conformers in the two polymorphs showed
      different electronic structures. The carboxylic group of one symmetrically
      different molecule in the alpha-form had significantly larger nuclear Fukui
      functions than those of other molecules of either the alpha- or gamma-form,
      supporting the experimental observation that the alpha-form was much more
      reactive with ammonia than the gamma-form. In addition, the large nuclear Fukui
      functions associated with atoms other than those from the carboxylic group were
      attributed to the tension of two dislodged aromatic rings. CONCLUSIONS:
      Electronic calculations were able to provide insightful glimpses into the effect
      of crystal packing on the solid-state reaction of indomethacin. The nuclear Fukui
      function, which characterizes the physical stress on an atom due to perturbation
      in electron density, may provide a powerful means of studying the solid-state
      reactions of organic crystals at the electronic level.

PMID- 16091994
TI  - The effect of formulation variables and breathing patterns on the site of nasal
      deposition in an anatomically correct model.
AB  - PURPOSE: This study was conducted to evaluate the effect of formulation variables
      and breathing patterns on aerosol distribution in the nasal cavity. METHODS:
      Placebo nasal spray formulations containing 0.25% w/v Avicel CL611 (viscosity = 4
      cP) and 2% w/v methylcellulose (MC; viscosity = 18.2 cP) were radiolabeled with
      (99m)Technicium. Following spraying into a silicone nose model, through which air
      was drawn at one of three constant rates (0, 10, and 20 L/min) or one of two
      breathing profiles (representing fast and slow inhalations), aerosol deposition
      in the model was quantified by gamma scintigraphy. Regional deposition was
      expressed as horizontal[inner, middle (h), outer] and vertical distribution
      [upper, middle (v), lower] in the nose model. RESULTS: Compared to 2% MC, Avicel
      CL611 significantly increased aerosol deposition in the middle (h) region of the
      nasal cavity under all breathing conditions, and in the inner region at 0 and 20
      L/min and with a slow inhalation. The different breathing rates showed no effect
      on deposition of 2% MC. However, 10 L/min significantly increased the upper
      deposition of Avicel compared to 0 and 20 L/min. CONCLUSIONS: Nasal sprays with a
      low viscosity provided greater surface coverage of the nasal mucosa than higher
      viscosity formulations. Changes in breathing profiles did not affect aerosol
      deposition in this nose model.

PMID- 16091996
TI  - Understanding the new clinical landscape for psoriasis: a comparative review of
      biologics.
AB  - BACKGROUND: Encouraging results from clinical trials suggest that biologic
      therapies are effective treatments for psoriasis. OBJECTIVE: The aim of our study
      was to evaluate the scientific evidence for the efficacy and safety of biologic
      drugs for psoriasis. METHODS: The studies reviewed include data on the biologies
      alefacept, efalizumab, etanercept, and infliximab. This article reviews all data
      published in the dermatology literature listed in the MEDLINE database, as well
      as data presented as abstracts and posters at dermatology society meetings,
      including the annual meetings of the American Academy of Dermatology. RESULTS:
      The majority of the studies used an improvement from baseline of 75% or more in
      the psoriasis area and severity index (PASI 75) as the primary measure of
      efficacy. CONCLUSIONS: Overall, biologics represent an important addition to the
      psoriatic therapies and have a great impact on the disease course and life
      quality of those afflicted with psoriasis.

PMID- 16091997
TI  - Safety and efficacy of tacrolimus ointment 0.1% (Protopic) in atopic dermatitis:
      a Canadian open-label multicenter study.
AB  - BACKGROUND: Most previously published trials of topical tacrolimus in atopic
      dermatitis were of relatively short duration and comprised a limited population
      with moderate-to-severe disease. OBJECTIVE: The goal of the study was to evaluate
      the safety and efficacy over a 6-month period of tacrolimus 0.1% ointment in
      children and adults with a broader severity spectrum of atopic dermatitis.
      METHODS: An open-label multicenter trial in patients 2 years and older was used.
      Primary safety and tolerability assessments included skin infection and
      application site adverse events. Efficacy parameters were body surface area
      involvement, pruritus score, and overall response. RESULTS: There were 240
      patients recruited at 23 study sites. Significant improvement from baseline was
      noted for all efficacy endpoints in both pediatric and adult patients. Skin
      infections occurred in 26% of patients. Burning sensation with product
      application, reported by 38% of patients, was transient and of mild-to-moderate
      severity in the majority. CONCLUSION: Tacrolimus 0.1% ointment was safe, well
      tolerated, and efficacious in treatment of atopic dermatitis in children and
      adults over six months.

PMID- 16091995
TI  - Membrane binding proteins are the major determinants for the hepatocellular
      transmembrane flux of long-chain fatty acids bound to albumin.
AB  - PURPOSE: The hepatic transmembrane flux of long-chain fatty acids (LCFA) occurs
      through passive and fatty acid transport protein facilitated processes from
      blood. The extent that these transport processes can be related to the unbound
      and protein-bound fractions of LCFA in blood is not clear. METHODS: We used
      hepatocyte suspensions, hepatoma monolayers, and perfused rat livers to
      quantitate the transport of purified [(3)H]palmitate ([(3)H]PA) and 12-(N-methyl)
      N-[(7-nitrobenz-2oxa-1,3-diazol-4yl-)amino]octadecanoicacid (12-NBDS) from
      solutions with a constant unbound LCFA concentration with varying bovine serum
      albumin (BSA) concentrations and in the presence and absence of antisera raised
      against cytosolic liver fatty acid binding protein (L-FABP). RESULTS: In the
      absence of L-FABP antisera, using an unbound ligand concentration that was
      adjusted to remain constant at each BSA concentration, hepatocyte [(3)H]PA and 12
      NBDS uptake rates increased linearly with an increase in BSA concentration (p <
      0.0001). In the presence of L-FABP antisera, [(3)H]PA uptake showed a greater
      reduction in the presence of 100 muM BSA than 5 muM BSA. The calculated
      permeability surface area product (PS) confirmed that both unbound and bound
      fractions of LCFA contributed to the overall flux, but only the PS for the
      protein-bound fraction was reduced in the presence of L-FABP antisera. In situ
      rat liver perfusion studies showed that the only rate process for the disposition
      of [(3)H]PA in the liver inhibited by L-FABP antisera was that for influx, as
      defined by PS, and that it reduced PS in the perfused liver by 42%. CONCLUSION:
      These results suggest that, at physiological albumin concentrations, most of the
      LCFA uptake is mediated from that bound to albumin by a hepatocyte basolateral
      membrane transport protein, and uptake of unbound LCFA occurring by passive
      diffusion contributes a minor component.

PMID- 16091998
TI  - Topical therapy for peristomal pyoderma gangrenosum.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon condition. Literature on the
      management of peristomal PG (PPG) is sparse. In the absence of randomized
      controlled trials the reporting of case series is potentially helpful to the
      management of this uncommon disease. OBJECTIVE: In this study we report our
      experience with topical corticosteroid therapy for 14 consecutive cases of PPG.
      METHODS: A clinical diagnosis PPG was made by a trained dermatologist using the
      appropriate investigations where necessary. RESULTS: The majority of the cases
      presented were managed with simple topical corticosteroids, occasionally in
      combination with a change of dressing. In 8/14 (57%) cases ulcer resolution was
      achieved within 3 months with topical treatment alone or topical treatment plus a
      change of dressing to a silicone-based product applied directly to the wound
      under the normal base plate of the stoma bag. CONCLUSION: Our experience suggests
      that a significant proportion of PPG can be managed by topical treatment alone.
      The simple topical treatment allows the patient to continue use of stoma care
      products while minimizing the potential for side effects.

PMID- 16092000
TI  - Abdominal elephantiasis: a case report.
AB  - BACKGROUND: Elephantiasis is a well-known condition in dermatology usually
      affecting the legs and external genitalia. It is characterized by chronic
      inflammation and obstruction of the lymphatic channels and by hypertrophy of the
      skin and subcutaneous tissues. The etiology is either idiopathic or caused by a
      variety of conditions such as chronic filarial disease, leprosy, leishmaniasis,
      and chronic recurrent cellulites. OBJECTIVE: Elephantiasis of the abdominal wall
      is very rare. A complete review of the English and French literature showed only
      two cases reported in 1966 and 1973, respectively. We report a third case of
      abdominal elephantiasis and we briefly review this entity. METHODS: We present
      the case of a 51-year-old woman who had progressively developed an enormous
      pediculated abdominal mass hanging down her knees. The skin was thickened,
      hyperpigmented, and fissured. She had a history of multiple abdominal cellulites.
      RESULTS: She underwent an abdominal lipectomy. Histopathology of the specimen
      confirmed the diagnosis of abdominal elephantiasis. CONCLUSION: Abdominal
      elephantiasis is a rare disease that represents end-stage failure of lymph
      drainage. Lipectomy should be considered in the management of this condition.

PMID- 16091999
TI  - Successful treatment of Von Zumbusch pustular psoriasis with infliximab.
AB  - BACKGROUND: Von Zumbusch pustular psoriasis is a severe, generalized form of
      psoriasis. Patients may also suffer from systemic complications, such as fever,
      arthropathy, congestive heart failure, and infections, which can ultimately prove
      fatal. Generalized pustular psoriasis can often be recalcitrant, making treatment
      difficult. OBJECTIVE: The purpose of this study was to demonstrate the efficacy
      of infliximab in treating generalized pustular psoriasis. METHODS: Four
      consecutively admitted patients with generalized pustular psoriasis were treated
      with infliximab 5 mg/kg intravenous infusion. RESULTS: After treatment with
      infliximab, white blood cell count, sedimentation rate, C-reactive protein, and
      vital signs normalized in all 4 patients within 24 h of the infusion. PASI scores
      on discharge had improved in all 4 patients. CONCLUSION: All 4 patients with
      generalized pustular psoriasis had rapid and positive responses to infliximab
      without any significant side effects. This experience adds support to the use of
      infliximab for generalized pustular psoriasis.

PMID- 16092001
TI  - Treatment of chronic nonhealing leg ulceration with gaseous nitric oxide: a case
      study.
AB  - BACKGROUND: Despite the best clinical practice, chronic nonhealing ulcers of the
      lower extremities present a significant challenge. Nitric oxide (NO) has been
      shown to play a significant role in biological functions including wound healing
      and as an antimicrobial agent in nonspecific immune response. OBJECTIVE: Our goal
      was to study the effect of gaseous NO (gNO) administered directly to a two-year
      old nonhealing chronic venous ulcer in a 55-year-old male presenting with a 30
      year history of severe venous disease. METHODS: gNO (200 ppm) was applied to the
      lower extremity using a delivery system connected to a "single patient use"
      plastic boot, at 1.0 L/min. RESULTS: The patient received an average of 8.1-h
      treatments for 14 consecutive nights. On day 0 the wound was malodorous and
      covered by bacterial biofilm with little healthy granulation tissue present.
      Following 3 days of gNO treatment, healthy granulation tissue was noted with
      absence of malodorous odor. At day 14, the ulcer was significantly reduced in
      size (p = 0.014) and almost completely reepithelialized. Day 10 post-treatment
      did not reveal any deterioration in healing. Six weeks later, the wound was 90%
      healed. At 26 weeks post gNO discontinuation, the ulcer was completely healed.
      CONCLUSIONS: This single case study demonstrated that gNO as a topical agent was
      well tolerated by the patient without any report of discomfort or side effect.
      The result of wound healing was very promising and warrants future exploration.

PMID- 16092002
TI  - Multiple keratoacanthomas arising post-UVB therapy.
AB  - BACKGROUND: Ultraviolet (UV) radiation is known to be an important etiologic
      agent in the development of skin cancer. Keratoacanthoma is an unusual, well
      described cutaneous neoplasm that resembles squamous cell carcinoma but
      spontaneously resolves. Rarely, multiple keratoacanthomas may develop. OBJECTIVE:
      We present a case of multiple keratoacanthomas in a patient with psoriasis who
      had received UVB phototherapy. These lesions were hyperkeratotic papules, many of
      which spontaneously resolved and demonstrated the histologic characteristics of
      keratoacanthoma. CONCLUSION: We believe that UV radiation is the most likely
      etiologic factor in this patient's development of multiple keratoacanthomas. We
      wish to bring to the attention of clinicians this unusual adverse effect of UV
      treatment.

PMID- 16092003
TI  - Prednicarbate (Dermatop): profile of a corticosteroid.
AB  - BACKGROUND: Topical steroids have been a popular choice for treating various
      cutaneous disorders; however, the potential for significant local and systemic
      adverse events, like skin atrophy and hypothalamic-pituitary-adrenal (HPA) axis
      suppression, has limited their use. OBJECTIVE: This article reviews the topical
      steroid prednicarbate through its mechanism of action, clinical efficacy, and
      adverse events profile. METHODS: Published literature containing the word
      "prednicarbate" was examined and summarized. RESULTS: Prednicarbate is a
      nonhalogenated, double-ester derivative of prednisolone that has been used in the
      treatment of inflammatory and pruritic manifestations of corticosteroid
      responsive dermatoses such as atopic dermatitis. It has a favorable benefit-risk
      ratio, low skin atrophy potential, and high anti-inflammatory action. CONCLUSION:
      These characteristics make prednicarbate an ideal alternative agent for children,
      elderly patients, and those who require long-term intermittent treatment.

PMID- 16092017
TI  - The "oy" of sex: a medical perspective.

PMID- 16092018
TI  - Reclassification will not make the pain go away.

PMID- 16092019
TI  - Is dyspareunia unrelated to early sexual abuse?

PMID- 16092020
TI  - Dyspareunia and DSM: a gynecologist's opinion.

PMID- 16092021
TI  - Weighing the pro's and con's of reclassifying dyspareunia.

PMID- 16092022
TI  - Why deny dyspareunia its sexual meaning?

PMID- 16092023
TI  - Classifying pain: what's at stake for women with dyspareunia.

PMID- 16092024
TI  - Adding insult to injury: the classification of dyspareunia as a sexual
      dysfunction in the DSM.

PMID- 16092025
TI  - A slightly different idea.

PMID- 16092026
TI  - Dyspareunia: a pain disorder or sexual dysfunction?

PMID- 16092027
TI  - Revisiting the diagnosis of dyspareunia: a painful but important discussion.

PMID- 16092028
TI  - Teasing apart the pain from the sex: is the pendulum swinging too far?

PMID- 16092029
TI  - Dyspareunia: another argument for removal.

PMID- 16092030
TI  - Making the case for sexual pain: let's not throw out the baby with the bath
      water.

PMID- 16092031
TI  - A rose by any other name: should dyspareunia be reclassified?

PMID- 16092032
TI  - A more radical proposal: dyspareunia is not a mental disorder.

PMID- 16092033
TI  - Dyspareunia is the only valid sexual dysfunction and certainly the only important
      one.

PMID- 16092034
TI  - Pain or sex?: choosing the best option.

PMID- 16092035
TI  - Sexual dysfunction or pain disorder?: dyspareunia from the perspective of the
      harmful dysfunction analysis.

PMID- 16092036
TI  - [Screening for depression -- two questions practically oriented].
AB  - Despite the high epidemiological relevance of depressive disorders in daily
      clinical practice, they are insufficiently diagnosed. For screening, the U.S.
      Preventive Services Task Force proposed two questions aiming at finding
      depressive core symptoms: "Over the past two weeks, have you felt down,
      depressed, or helpless?" and "Over the past two weeks, have you felt little
      interest or pleasure in doing things?". We tested comparable questions in a
      representative sample from the German population. The correlations between the
      screening and validated questionnaires for depression point towards the validity
      of the screener. Relevant indices are satisfying: For major depression the
      sensitivity is 72.6% and specificity is 87.4%.

PMID- 16092037
TI  - [Psychopharmacotherapy in somatic diseases -- treatment principles in daily
      medical routine].
AB  - Up to 46.5% of general hospital inpatients suffer from clinically relevant
      psychiatric disorders. Appropriate psychopharmacotherapy of comorbid mental
      disorders in the medically ill can have positive effects on the course of somatic
      illness and can enhance quality of life in patients with medical or neurologic
      conditions. However, treating psychiatric disorders in this population can often
      be challenging, even for the most seasoned clinicians. An increasingly important
      issue in daily medical routine when prescribing medications is the possibility
      that a newly prescribed drug may interact with existing pharmacotherapy. Most
      often the concern is to avoid adverse consequences, such as undermining the
      effectiveness of previously stable drug therapy or precipitating the appearance
      of new adverse events. We have used the examples of Parkinson's disease, epilepsy
      and cardiovascular disease commonly associated with mental disorders to
      illustrate how these considerations affect the clinician's choice of a
      psychotropic drug in the medically ill.

PMID- 16092038
TI  - [Gamma-hydroxy butyric acid: neurotransmitter, sedative and party drug].
AB  - Gamma-hydroxybutyric acid (GHB) as a natural component of the mammalian brain was
      first introduced in clinical anaesthesic practice more than 40 years ago. The
      drug was nearly forced from clinical practice because of its prolonged and
      variable duration of action. The results of recent clinical studies indicate a re
      evaluation of GHB in various clinical fields. In the intensive care unit, GHB may
      be a favourable alternative to established drugs. The results of various clinical
      studies also suggest that GHB is efficacious in the treatment of alcohol
      withdrawal syndrome, and narcolepsy. GHB has been used successfully for short
      term sedation in children. In addition, GHB has emerged as a street drug ("liquid
      ecstasy"). Overdose may lead to respiratory depression, coma, and even death.
      Chronic abuse itself may lead to severe withdrawal syndrome. The purpose of this
      article is to outline the neurophysiological, pharmacodynamic and pharmacokinetic
      characteristics of GHB, and to summarize the potential fields of use and misuse
      of GHB in clinical medicine and toxicology.

PMID- 16092039
TI  - [Travel behavior of the Austrians -- review and future trends].
AB  - In the past decades, international travel has expanded exponentially and
      therefore its economic significance has increased. This development has been made
      possible purely by the enormous increase in scheduled and charter flights. Travel
      frequency has also increased among practically all age groups. The manifold
      travel destinations extend virtually to the whole globe. Europe has been able to
      maintain its status as premier destination for tourists. Europe has a 50% share
      of the global income from international travel. The clear up-swing of the travel
      branch in the year 2002 could not be continued in 2003. The desire to travel was
      present, but the trend to short travel has continued. Three years after the
      events of 11 September 2001, experts again expect an increase in travel frequency
      and intensity on the part of European tourists for the next years. The World
      Tourism Organisation prognosticates an enormous growth in international tourist
      arrivals up to 2020. Despite continuing globalization, international tourism will
      continue to take place primarily within the individual regions of the world.

PMID- 16092040
TI  - [Health campaign for atherosclerosis prevention].
AB  - The goal of the campaign "plus leben", a project designed to run for at least 5
      years, is to heighten the awareness of patients at risk of heart disease and to
      provide them with an appropriate prevention program. During the first two years
      of the campaign 20,000 visitors were registered on the homepage, 400,000 tests
      for risk of heart disease were distributed, and more than 3,000 health
      information brochures were requested. Thus, a survey of patients was designed to
      provide information on the extent to which preventive measures are effective. The
      survey, which was carried out by mail, had a response rate of 28%, or 230
      participants. In the random sample, consisting of about 60% men and 40% women,
      only 16% are younger than 50 years of age. Thus the survey provides a
      representative picture of the affected target group. The test for risk of cardiac
      disease provided by "plus leben" led to an increase in awareness of preventive
      measures in more than two thirds of the respondents, and 60% also completed the
      test. Although only a fourth of the patients are regularly informed by their
      physician about preventive measures, the campaign has led about 90% of the
      respondents to make fundamental or at least partial changes in their lifestyle.
      In connection with the study it was shown that the media play an important role
      in providing information on preventive measures. Communication in the doctor's
      office as an important building block in raising consciousness about
      atherosclerosis prevention could be further improved.

PMID- 16092041
TI  - [Examination of stability and compatibility of flucloxacillin (Floxapen) and
      ceftazidime (Fortum) in two infusion media: relevance for the clinical praxis].
AB  - Flucloxacillin (Floxapen) and ceftazidime (Ceftazidim) are both highly active
      antibiotics against Gram-positive and Gram-negative organisms, respectively.
      Because of their complementary spectra of activity, simultaneous administration
      of both drugs via continuous infusion is highly favored by clinicians. Therefore,
      the aim of the present study was to examine the stability and compatibility of
      both drugs in Aqua ad injections and in physiological solution of sodium chloride
      in the presence and absence of furosemide (Lasix). Physical and chemical
      stability were examined using different concentrations of flucloxacillin (2-12
      g/50 ml) and ceftazidime (2-9 g/50 ml). On the basis of a limit of max. 10%
      degradation, flucloxacillin and ceftazidime can be considered stable at 4 degrees
      C and room temperature for up to 24 hours. Neither concentration nor infusion
      medium had significant influence on the degradation of both compounds. Addition
      of furosemide (250 mg/50 ml) does not cause any incompatibilities or significant
      decrease of the antimicrobial drug concentrations.

PMID- 16092045
TI  - IPF-1/MODY4 gene missense mutation in an Italian family with type 2 and
      gestational diabetes.
AB  - Maturity-onset diabetes of the young (MODY) is a monogenic autosomal-dominant
      form of diabetes mellitus with onset before 25 years of age. Genetic variation in
      insulin promoter factor-1 (IPF1) (MODY4) is uncommon but may contribute to early-
      or late-onset diabetes as part of a polygenic background. IPF1 is a homeodomain
      transcription factor required for pancreas development. Our aim was to identify
      whether IPF1 gene mutations play a role in Italian early-onset type 2 diabetic
      (T2D) patients and what functional impact mutations may have in the beta cell. We
      screened 40 Italian early-onset type 2 diabetic probands for IPF1 mutations,
      performed oral glucose tolerance tests in the unaffected family members, and
      performed in vitro functional studies of the mutant variant. In an extended
      family (Italy-6) of 46 members with clinical phenotypes of gestational diabetes,
      MODY, and T2D, a single nucleotide change of CCT to ACT was identified at codon
      33 resulting in a Pro to Thr substitution (P33T) in the IPF1 transactivation
      domain that also contributes to an altered metabolic status in the unaffected NM
      subjects. Of the 22 genotyped Italy-6 members, 9 carried the P33T allele (NM), of
      whom 5 have either T2D or elevated fasting glucose levels. Oral glucose tolerance
      tests showed higher glucose levels at 90 minutes in unaffected NM compared with
      unaffected NN subjects. Of the 5 female pregnant carriers of the IPF1 mutation, 4
      had pregnancies complicated by reduced birth weights, miscarriages, or early
      postnatal deaths. In studies in vitro, the IPF1 mutant protein (P33T) showed a
      reduction in DNA-binding and transcriptional activation functions as compared to
      the wild-type IPF1 protein. Our findings suggest that the P33T IPF1 mutation may
      provide an increased susceptibility to the development of gestational diabetes
      and MODY4 in the Italy-6 pedigree.

PMID- 16092046
TI  - Effect of a single vs multiple bouts of exercise on glucose control in women with
      type 2 diabetes.
AB  - The Surgeon General and Centers for Disease Control and Prevention have
      recommended that multiple bouts of exercise can be accumulated throughout the day
      in lieu of the more traditional single, longer bout of exercise. Yet, conclusive
      evidence does not exist suggesting these 2 training modes provide similar health
      related benefits on metabolic control, especially in individuals with type 2
      diabetes. The purpose of this study was to determine if differences exist in
      glucose control when preceded by one 30-minute or three 10-minute bouts of
      exercise in women with type 2 diabetes. Nine individuals with type 2 diabetes (53
      +/- 6 years old) and 6 control women (49 +/- 4 years old) completed 3 randomly
      ordered oral glucose tolerance tests (OGTTs). Two of the OGTTs were preceded the
      day prior by moderate exercise (approximately 60% of Vo2peak), either one 30
      minute or three 10-minute bouts, whereas the third OGTT was used as a control day
      with no exercise performed 3 days prior. Glucose and insulin were measured every
      30 minutes for 4 hours during the OGTT. Individuals with type 2 diabetes
      exhibited a greater overall glucose response than the controls (P < .05), but the
      glucose response to the OGTT was not different between the 3 conditions within
      each group (2-hour glucose: multiple bout, 14.3 +/- 3.2 vs 5.0 +/- 1.7; single
      bout, 14.1 +/- 3.0 vs 4.7 +/- 1.5; control day, 14.6 +/- 2.7 vs 4.9 +/- 4.9
      mmol/L). Glucose area under the curve analysis resulted in similar findings. As
      expected, the group with type 2 diabetes had greater fasting insulin levels
      compared with the control group for all exercise conditions (multiple bout: 4.5
      +/- 1.2 vs 0.3 +/- 0.2; single bout: 6.4 +/- 1.6 vs 0.9 +/- 0.4; control day: 5.7
      +/- 1.8 vs 1.5 +/- 0.6 pmol/L; P < .05). Exercise or no exercise did not alter
      the insulin response to the OGTT for either group. Despite a higher glucose
      response to the glucose load in T2D, an acute exercise bout (single or multiple
      bouts) did not appear to alter glucose control the following day in either the
      individuals with type 2 diabetes or the control group.

PMID- 16092047
TI  - Physiological difference between obese (fa/fa) Zucker rats and lean Zucker rats
      concerning adiponectin.
AB  - Obese (fa/fa) Zucker rat is a spontaneous genetic obesity model and, by
      comparison with lean Zucker rat, exhibits hyperphagia, hyperinsulinemia, and
      hyperlipidemia. The aim of this study was to examine the physiological difference
      concerning adiponectin between obese (fa/fa) Zucker rats and control lean Zucker
      rats. We therefore measured plasma adiponectin level and analyzed adiponectin and
      adiponectin receptor 1 mRNA expression in retroperitoneal white adipose tissue
      (RT WAT), brown adipose tissue (BAT), liver, and soleus muscle. We also examined
      the tissue mRNA expression of peroxisome proliferator-activated receptor alpha
      (PPAR alpha), PPAR delta, and PPAR gamma, which regulate adiponectin expression
      sensitivity to a PPAR gamma agonist shown by brown adipocytes from obese (fa/fa)
      Zucker rats and lean Zucker rats, by measuring adiponectin release from these
      cells. Plasma adiponectin levels of obese (fa/fa) Zucker rats were significantly
      higher than those of lean Zucker rats. Adiponectin mRNA expression levels in RT
      WAT were lower in obese (fa/fa) Zucker rats than in lean Zucker rats, but those
      in BAT were higher. Adiponectin receptor 1 expression levels in RT WAT, BAT, and
      liver of obese (fa/fa) Zucker rats were lower than in lean Zucker rats. The
      expression level of PPAR alpha, PPAR delta, and PPAR gamma in BAT was lower in
      obese (fa/fa) Zucker rats than in lean Zucker rats. Moreover, the PPAR gamma
      agonist increased adiponectin release only from the brown adipocytes isolated
      from lean Zucker rats. It is the conclusive difference between obese (fa/fa)
      Zucker rats and lean Zucker rats that plasma adiponectin levels of obese (fa/fa)
      Zucker rats are significantly higher than those of lean Zucker rats. Moreover, we
      clarified that mRNA expression level of adiponectin receptor 1 in RT WAT, BAT,
      and liver of obese (fa/fa) Zucker rats is low despite high plasma adiponectin
      level, and low expression of PPARs in BAT leads to less sensibility of
      adiponectin release from brown adipocytes to a PPAR gamma agonist in obese
      (fa/fa) Zucker rats.

PMID- 16092048
TI  - A novel advanced glycation index and its association with diabetes and
      microangiopathy.
AB  - Formation of advanced glycation end products (AGEs) is an important mechanism by
      which chronic exposure to high glucose levels leads to vascular complications.
      Measurement of AGEs is hence of great importance for clinicians and researchers
      concerned with the management and prevention of diabetic vascular disease. The
      aim of this study was to evaluate a simple methodology to detect AGEs in the
      serum and to correlate their levels with diabetes and microangiopathy,
      specifically retinopathy and nephropathy. We studied 157 subjects, which included
      nondiabetic control subjects (n = 38), type 2 diabetic patients without
      microangiopathy (n = 65), and type 2 diabetic subjects with retinopathy (n = 29)
      or both retinopathy and nephropathy (n = 25). All subjects were assessed for
      their glycemic and lipid status. Serum AGEs were monitored by recording the
      Maillard-specific fluorescence that resulted from sequential addition of serum
      into the buffer. The resultant linear regression was modeled to yield the slope
      values that were termed advanced glycation index (AGI) in arbitrary units. The
      serum levels of AGI (mean +/- SD) were higher in diabetic subjects without
      complications (6.0 +/- 1.6 units) compared with nondiabetic subjects (4.6 +/- 1.0
      units), still higher among diabetic subjects with retinopathy (7.6 +/- 1.2 units)
      and highest in diabetic subjects with both retinopathy and nephropathy (8.3 +/-
      2.0 units). Among diabetic subjects, AGI had a significant positive correlation
      with duration of diabetes (r = 0.25, P = .006), glycated hemoglobin (r = 0.27, P
      = .004), cholesterol (r = 0.24, P = .009), triglycerides (r = 0.23, P = .014),
      and serum creatinine (r = 0.30, P = .001), and a significant negative correlation
      with creatinine clearance (r = -0.27, P = .003). Logistic regression analysis
      using diabetic microangiopathy as the dependent variable showed an association
      with AGI even after including age, duration of diabetes, and glycated hemoglobin
      (P < .001) into the model. Advanced glycation index is a simple method to detect
      AGEs, and it correlates well with diabetes, particularly with microangiopathy.

PMID- 16092049
TI  - Brain glucose concentrations in poorly controlled diabetes mellitus as measured
      by high-field magnetic resonance spectroscopy.
AB  - Hyperglycemia and diabetes alter the function and metabolism of many tissues. The
      effect on the brain remains poorly defined, but some animal data suggest that
      chronic hyperglycemia reduces rates of brain glucose transport and/or metabolism.
      To address this question in human beings, we measured glucose in the occipital
      cortex of patients with poorly controlled diabetes and healthy volunteers at the
      same levels of plasma glucose using proton magnetic resonance spectroscopy.
      Fourteen patients with poorly controlled diabetes (hemoglobin A 1c = 9.8% +/-
      1.7%, mean +/- SD) and 14 healthy volunteers similar with respect to age, sex,
      and body mass index were studied at a plasma glucose of 300 mg/dL. Brain glucose
      concentrations of patients with poorly controlled diabetes were lower but not
      statistically different from those of control subjects (4.7 +/- 0.9 vs 5.3 +/-
      1.1 micromol/g wet wt; P = .1). Our sample size gave 80% power to detect a
      difference as small as 1.1 micromol/g wet wt. We conclude that chronic
      hyperglycemia in diabetes does not alter brain glucose concentrations in human
      subjects.

PMID- 16092050
TI  - Influence of apolipoprotein E genotype on the reliability of the Friedewald
      formula in the estimation of low-density lipoprotein cholesterol concentrations.
AB  - Lipoprotein data and apolipoprotein (apo) E genotype from 1302 participants,
      covering a wide range of total plasma cholesterol levels, were used to examine
      the impact of apo E genotype on the estimation of low-density lipoprotein
      cholesterol (LDL-C0 concentrations by the Friedewald formula using high-density
      lipoprotein cholesterol and triglyceride (TG) concentrations as compared with the
      beta -quantification reference procedure. The results showed that participants
      with apo E2/E2 genotype had significantly higher very low-density lipoprotein
      cholesterol (VLDL-C) concentrations and VLDL-C/TG ratio as well as lower LDL-C
      concentrations than participants with other apo E genotypes. Heterozygous
      carriers of the epsilon 2 allele had significantly higher VLDL-C than
      participants with apo E3/E3 and E4/E3 genotypes. The mean absolute error and the
      mean percentage of bias in calculated LDL-C according to all apo E genotypes,
      except E2/E2 genotype, were less than 0.16 mmol/L and 4.4%, respectively. Indeed,
      the mean error and the mean percentage of bias associated with the LDL-C
      calculated by the Friedewald formula in the apo E2/E2 group were 0.93 mmol/L and
      40.6%, respectively. However, participants with the apo E2/E2 genotype and a type
      III phenotype showed a mean error and a mean percentage of bias reaching 1.53
      mmol/L and 63.5%, respectively, whereas E2/E2 participants with a non-type III
      phenotype had a mean error and a mean percentage of bias of 0.18 mmol/L and
      11.0%, respectively. Moreover, 41.9% to 57.1% of the participants had an absolute
      bias higher than 5% according to the apo E genotype, except for the apo E2/E2
      genotypic group where 88.6% of the participants had an absolute bias higher than
      5%. Stepwise multiple linear regression analyses revealed that the apo E genotype
      contributed to 39.0% of the VLDL-C/TG ratio variance, whereas sex, age, and high
      density lipoprotein cholesterol explained between 0.5% and 3.2% of the variance.
      These results indicate that the apo E genotype exerts a significant influence on
      the estimation of LDL-C concentrations by the Friedewald formula as compared with
      the beta-quantification.

PMID- 16092051
TI  - Soluble adhesion molecules (sICAM-1, sVCAM-1) and selectins (sE selectin, sP
      selectin, sL selectin) levels in children and adolescents with obesity,
      hypertension, and diabetes.
AB  - The attachment of monocytes and lymphocytes to endothelial cells, which initiates
      atherosclerosis, arises under the influence of adhesion molecules. The
      preclinical phase of this disease lasts many decades, and this provides an
      opportunity for the presymptomatic detection of high-risk subjects. We evaluated
      levels of the adhesion molecules: sICAM-1 (soluble intercellular adhesion
      molecule 1), sVCAM-1 (soluble vascular adhesion molecule 1), sE selectin, sP
      selectin, and sL selectin in children with atherosclerosis risk factors (n = 123,
      mean age 15.1 years) (obese [n = 17], hypertensive [n = 25], obese with
      hypertension [n = 30], type 1 diabetic [n = 51]). Twenty-seven healthy children
      formed the control group, mean age 15.2 years. sICAM-1 was higher in the study
      group compared with control (314.1 +/- 61 vs 264.9 +/- 55 ng/mL, P < .01). The
      same was found for sVCAM-1 (513.7 +/- 187 vs 407.9 +/- 76 ng/mL, P < .05) and E
      selectin (86.04 +/- 33.6 vs 62.1 +/- 20.3 ng/mL, P < .01). sP-selectin and sL
      selectin levels were not different compared with controls. E selectin correlated
      with body mass index (BMI; r = 0.18, P = .03), total cholesterol (r = 0.2, P =
      .016), and triglycerides (r = 0.22, P = .008). sICAM-1 correlated with BMI (r =
      0.19, P = .019) and systolic blood pressure (r = 0.13, P = .045). In multiple
      linear regression analysis, sE selectin was found to be associated with
      triglycerides (R2 = 0.29, P = .045), sICAM-1 dependent on BMI (R2 = 0.58, P =
      .047), and sVCAM-1 dependent on total cholesterol (R2 = 0.51, P = .006). Elevated
      concentrations of sICAM-1, sVCAM-1, and E selectin were found in obese,
      hypertensive, and diabetic children. We conclude that endothelial activation
      appears in these children, and adhesion molecules are related to the earliest
      stages of atherosclerosis.

PMID- 16092052
TI  - Transaldolase is part of a supramolecular complex containing glucose-6-phosphate
      dehydrogenase in human neutrophils that undergoes retrograde trafficking during
      pregnancy.
AB  - Previous studies have shown that glucose-6-phosphate dehydrogenase (G6PDase) and
      6-phosphogluconate dehydrogenase form a supramolecular complex in human
      neutrophils that undergoes retrograde trafficking in cells from pregnant women,
      but anterograde trafficking in cells from nonpregnant individuals. Using
      fluorescence resonance energy transfer techniques, we now demonstrate that
      transaldolase (TALase), a key regulatory enzyme in the nonoxidative branch of the
      hexose monophosphate shunt, is in close physical proximity with G6PDase, but not
      with lactate dehydrogenase, thus suggesting the formation of a TALase-G6PDase
      complex. Moreover, immunofluorescence microscopy demonstrated that TALase
      undergoes anterograde trafficking in neutrophils from nonpregnant individuals,
      whereas retrograde trafficking is found during pregnancy. However, pregnancy did
      not affect lactate dehydrogenase distribution. Colchicine treatment blocked the
      retrograde distribution of TALase, suggesting that microtubules are involved in
      TALase trafficking. We suggest that TALase is part of a supramolecular hexose
      monophosphate shunt complex, which likely increases the efficiency of the shunt
      via substrate channeling. We further suggest that TALase's retrograde motion
      contributes to uncoupling the shunt from its source of glucose-6-phosphate at the
      plasma membrane, thereby blunting nicotinamide adenine dinucleotide phosphate
      (reduced form) production and downstream oxidant production by neutrophils.

PMID- 16092053
TI  - Contribution of age and declining androgen levels to features of the metabolic
      syndrome in men.
AB  - Plasma dehydroepiandrosterone sulfate (DHEA-S) and testosterone levels both
      decline with age in healthy men. Features of the metabolic syndrome also show age
      related deteriorations. We examined the relative contribution of age and
      declining androgen levels to features of the metabolic syndrome in men. In a
      sample of 130 nonsmoking men from the Quebec Family Study, we tested the
      hypothesis that age-related decreases in DHEA-S and testosterone levels would
      explain most of the variance in alterations of the metabolic profile associated
      with aging. As expected, we found that plasma DHEA-S and testosterone levels were
      negatively associated with age. Significant negative correlations were found
      between androgen levels and adiposity measures, body fat distribution, and
      metabolic risk variables. Statistical control for age eliminated correlations
      with DHEA-S, whereas age-adjusted associations between testosterone and most
      adiposity and metabolic variables remained significant. The percentage frequency
      of men characterized by 3 or more features of the metabolic syndrome increased
      with decreasing testosterone (8.9%-44.2%, chi2 = 15.89, P < .0005 ) and DHEA-S
      levels (8.9%-41.5%, chi2 = 13.02, P < .005). Logistic regression analyses showed
      that men in the upper tertile of testosterone levels had a lower risk of being
      characterized by 3 or more features of the metabolic syndrome (odds ratio = 0.24,
      P < .04) independent of age, whereas tertiles of DHEA-S levels were not related
      to the metabolic syndrome independent of age. In conclusion, results suggest that
      age per se is an important correlate of the associations between DHEA-S and
      metabolic variables, whereas the association of plasma testosterone levels to
      features of the metabolic syndrome appears to be independent of age.

PMID- 16092054
TI  - Leptin decreases lipogenic enzyme gene expression through modification of SREBP
      1c gene expression in white adipose tissue of aging rats.
AB  - Aging is associated with a significant reduction of lipogenic enzyme gene
      expression and lipogenesis in white adipose tissue (WAT). The age-related
      increase of lep gene expression could be, in part, responsible for these changes.
      Considering that sterol regulatory element binding protein 1c (SREBP-1c) plays an
      important role in regulation of lipogenic enzyme gene expression, it is likely
      that the age-related decrease of WAT lipogenic potential could be a consequence
      of the inhibition of SREBP-1c gene expression by leptin. We determined whether
      the increase of lep gene expression would account for the age-related decrease in
      SREBP-1c and its direct target, main lipogenic enzymes acetyl-CoA carboxylase
      (ACC) and fatty acid synthase (FAS), by assaying the messenger RNA (mRNA) levels
      of SREBP-1c, FAS, ACC, and leptin in WAT of 2-month-old (young) and 20-month-old
      (old) rats. Leptin mRNA level was much higher in the old animals, whereas in
      contrast, old rats displayed much lower mRNA levels of SREBP-1c and lipogenic
      enzymes. Moreover, experimentally increased plasma leptin concentration in young
      rats to the value observed in old rats resulted in the decrease of SREBP-1c, FAS,
      and ACC mRNA levels in WAT. Thus, the increase of lep gene expression could, in
      part, account for the reduced SREBP-1c gene expression and, consequently, the
      diminished lipogenic activity in WAT of old animals.

PMID- 16092055
TI  - Substrate availability and transcriptional regulation of metabolic genes in human
      skeletal muscle during recovery from exercise.
AB  - In skeletal muscle of humans, transcription of several metabolic genes is
      transiently induced during recovery from exercise when no food is consumed. To
      determine the potential influence of substrate availability on the
      transcriptional regulation of metabolic genes during recovery from exercise, 9
      male subjects (aged 22-27) completed 75 minutes of cycling exercise at 75% Vo2
      max on 2 occasions, consuming either a high-carbohydrate (HC) or low-carbohydrate
      (LC) diet during the subsequent 24 hours of recovery. Nuclei were isolated and
      tissue frozen from vastus lateralis muscle biopsies obtained before exercise and
      2, 5, 8, and 24 hours after exercise. Muscle glycogen was restored to near
      resting levels within 5 hours in the HC trial, but remained depressed through 24
      hours in the LC trial. During the 2- to 8-hour recovery period, leg glucose
      uptake was 5- to 15-fold higher with HC ingestion, whereas arterial plasma free
      fatty acid levels were approximately 3- to 7-fold higher with LC ingestion.
      Exercise increased (P < .05) transcription and/or mRNA content of the pyruvate
      dehydrogenase kinase 4, uncoupling protein 3, lipoprotein lipase, carnitine
      palmitoyltransferase I, hexokinase II, peroxisome proliferator activated receptor
      gamma coactivator-1 alpha, and peroxisome proliferator activated receptor alpha.
      Providing HC during recovery reversed the activation of pyruvate dehydrogenase
      kinase 4, uncoupling protein 3, lipoprotein lipase, and carnitine
      palmitoyltransferase I within 5 to 8 hours after exercise, whereas providing LC
      during recovery elicited a sustained/enhanced increase in activation of these
      genes through 8 to 24 hours of recovery. These findings provide evidence that
      factors associated with substrate availability and/or cellular metabolic recovery
      (eg, muscle glycogen restoration) influence the transcriptional regulation of
      metabolic genes in skeletal muscle of humans during recovery from exercise.

PMID- 16092056
TI  - Chronic ethanol feeding controls the activities of various sialidases by
      regulating their relative synthetic rates in the rat liver.
AB  - We have determined the concentration effects of feeding for 8 weeks 10.8%, 21.6%,
      and 36% dietary ethanol calories on the activities and relative synthetic rates
      (RSRs) of various subcellular sialidases of rat liver. The hepatic RSRs of each
      species of sialidase was determined based on the ratio of 1-hour incorporation of
      [35S]-methionine into immunoprecipitable sialidase as percent of the
      incorporation into total protein in each subcellular fraction. Ganglioside
      sialidase activities in the hepatic subcellular fractions were also determined.
      Ethanol feeding at 36% dietary calories caused an increase in the ganglioside
      sialidase activity of the plasma membrane sialidase (PMS) by 232% (P < .01) and
      that of cytosolic sialidase (CS) by 184% (P < .05), but decreased the lysosomal
      membrane sialidase (LMS) by 54% (P < .01) when compared with the control animals.
      The specificity of each antisialidase antibody was verified by immunoblots. The
      RSR of PMS was increased by 40% (P < .01), 67% (P < .01), and 220% (P < .01) in
      the 10.8%, 21.6%, and 36% ethanol groups, respectively. Similarly, the RSR of CS
      was increased by 17% (P < .01), 19% (P < .01), and 63% (P < .01), respectively,
      in these ethanol groups. In contrast, the RSR of LMS was inhibited by 36% (P <
      .01), 34% (P < .01), and 69% (P < .01), respectively, in these ethanol groups.
      Intralysosomal sialidase failed to hydrolyze gangliosides. Thus, PMS and CS, but
      not LMS or intralysosomal sialidase, may play important roles in ethanol
      modulated desialylation of gangliosides and consequent liver injury and
      behavioral alterations.

PMID- 16092057
TI  - Targeting vascular risk in patients with metabolic syndrome but without diabetes.
AB  - There are no prospective data on the effect of a multitargeted treatment approach
      on cardiovascular disease (CVD) risk reduction in nondiabetic patients with
      metabolic syndrome (MetS). Furthermore, the optimal hypolipidemic drug treatment
      in these patients remains controversial. In this prospective, randomized, open
      label, intention-to-treat, and parallel study, 300 nondiabetic patients with
      MetS, free of CVD at baseline, were studied for a period of 12 months. Age- and
      sex-matched subjects without MetS (n = 100) acted as controls. All patients
      received lifestyle advice and a stepwise-implemented drug treatment of
      hypertension, impaired fasting glucose, and obesity. For hypolipidemic treatment,
      the patients were randomly allocated to 3 treatment groups: atorvastatin (n =
      100, 20 mg/d), micronized fenofibrate (n = 100, 200 mg/d), and both drugs (n =
      100). Clinical and laboratory parameters, including the lipid profile and C
      reactive protein (CRP), were assessed at the baseline and at the end of the
      study. The primary end point was the proportion of patients not having MetS or
      its component features at the end of the 12-month treatment period. The secondary
      end points were the difference in 10-year CVD risk (Prospective Cardiovascular
      Munster risk calculator) and the degree of CRP reduction. By the end of the
      study, 76% of the patients no longer had MetS, and 46% had only one diagnostic
      MetS factor. The estimated 10-year (Prospective Cardiovascular Munster) risk of
      all patients with MetS at baseline was 14.6%. This was reduced in the
      atorvastatin group to 6.4%, in the fenofibrate group to 9.2%, and in the
      combination group to 5.5% (P < .0001 for all vs baseline). The 10-year risks of
      the atorvastatin and combination groups were not different from that of the
      control group (5.0%). C-reactive protein was significantly reduced in all
      treatment groups, with the atorvastatin and combination groups having the
      greatest reduction (65% and 68%, respectively, P < .01 vs the fenofibrate group,
      44%). Lipid values were significantly improved in all 3 treatment groups, with
      those on the combined treatment attaining lipid targets to a greater extent than
      those in the other 2 groups. A target-driven and intensified intervention aimed
      at multiple risk factors in nondiabetic patients with MetS substantially offsets
      its component factors and significantly reduces the estimated CVD risk. The
      atorvastatin-fenofibrate combination had the most beneficial effect on all lipid
      parameters and significantly improved their CVD risk status. Atorvastatin and
      combination treatment were more effective than fenofibrate alone in reducing CRP
      levels.

PMID- 16092058
TI  - Low-density lipoprotein apolipoprotein B production differs between laboratory
      opossums exhibiting high and low lipemic responses to dietary cholesterol and
      fat.
AB  - Two partially inbred strains of laboratory opossums exhibit extremely high or low
      levels of low-density lipoprotein (LDL) cholesterol concentrations, respectively,
      when challenged with a high-cholesterol and high-fat (HCHF) diet. The present
      studies were conducted to determine whether the catabolism or the production of
      LDL apolipoprotein B (apoB) is responsible for the variability in plasma LDL
      cholesterol and apoB concentrations. Iodinated LDL prepared from plasma of donor
      opossums consuming HCHF diet was injected into high- and low-responding
      recipients maintained on the HCHF diet. Blood was drawn at intervals beginning at
      3 minutes and ending at 24 hours. At the end of the study, animals were
      necropsied, and livers were removed for isolation of RNA. Plasma LDL apoB was
      separated by sodium dodecyl sulfate-electrophoresis, and the level of
      radioactivity was determined. Hepatic LDL receptor and apoB mRNA levels were
      measured by Northern blotting. Radioactivity decay curves were plotted by using
      the radioactivity at each time point as percentage of the radioactivity recovered
      at 3 minutes. Fractional catabolic rates (FCRs) were calculated by the curve
      peeling technique. Steady-state production rates were calculated by multiplying
      the FCR values with apoB concentrations. LDL apoB FCR was slightly higher (1.63
      fold) in low responders than in high responders. On the other hand, LDL apoB
      production was much higher (5.5-fold) in high responders than in low responders.
      There was no difference in hepatic mRNA levels for either the LDL receptor or
      apoB. The differences in LDL apoB FCR may be explained on the basis of
      differences in pool size between the 2 strains. Therefore, LDL apoB production is
      the major determinant of diet-induced hyperlipidemia in laboratory opossums.
      Because LDL apoB production was not associated with hepatic mRNA levels, the
      production of LDL apoB is regulated posttranscriptionally or posttranslationally.

PMID- 16092059
TI  - Mutations in low-density lipoprotein receptor gene as a cause of
      hypercholesterolemia in Taiwan.
AB  - Familial hypercholesterolemia (FH) is inherited as an autosomal dominant trait
      that has been associated with more than 920 different mutations in the low
      density lipoprotein receptor (LDLR) gene. To characterize LDLR gene mutations in
      the Chinese of Han descent with FH, we isolated genomic DNA from peripheral blood
      samples of 20 affected subjects and 50 healthy subjects with no family history of
      hypercholesterolemia. We used polymerase chain reaction and long polymerase chain
      reaction to amplify the 18 coding exons and the minimal promoter of the LDLR
      gene, and subjected amplicons to direct sequence analysis. We identified 6
      mutations in LDLR gene, including heterozygous missense mutations I420T (ATC-
      >ACC), C660W (TGC-->TGG), H562Y (CAC-->TAC), and A606T (GCC-->ACC), and a
      heterozygous and a homozygous mutation in codon P664L (CCG-->CTG) as well as a
      homozygous large deletion of exons 6 to 8. The FH homozygotes manifested
      generalized xanthomatosis. One of the mutations we identified (C660W) was novel.
      In conclusion, we identified 5 missense mutations and 1 large deletion in LDLR
      gene, including 1 novel mutation in Han Chinese with FH in Taiwan.

PMID- 16092060
TI  - The endothelial cholesterol efflux is promoted by the high-density lipoprotein
      anionic peptide factor.
AB  - The prevention of atherosclerosis depends on the high-density lipoprotein (HDL)
      capacity to stimulate the efflux of unesterified cholesterol (UC). We tested here
      the effects of 2 HDL apolipoproteins, apo A-I and the 7-kd anionic peptide factor
      (APF), on the UC efflux by human endothelial ECV 304 cells in culture.
      Apolipoprotein A-I (10 micromol/L) or APF (3.5 micromol/L) in lipid-free forms or
      small particles (13 nm with apo A-I or 19 nm with APF) were incubated in the
      presence of [4-14C]UC. The phosphatidylcholines (PCs) were present either at a
      low level (0.35 mmol/L with apo A-I or 0.20 mmol/L with APF) or at a high level
      (1 mmol/L with apo A-I). We also tested either large 53-nm bile lipoprotein
      complex-like particles (3.5 micromol/L APF [13 microg/500 microL]) with a high PC
      level (0.65 mmol/L) or a 9-residue synthetic peptide (13 microg/500 microL),
      derived from the NH2-terminal domain of HDL3-APF, in a lipid-free or low
      lipidated (0.20 mmol/L PCs) form. A control was developed in absence of the added
      compounds. A rapid [4-14C]UC efflux mediated by APF added in free form or in 19
      nm complexes was 2.2- to 2.3-fold higher than that mediated by apo A-I in free
      form or in 13-nm particles (P < .05). The level of this high APF-related efflux
      was comparable with that obtained with the 12-nm native HDLs (10 micromol/L apo A
      I) or free PCs (1 mmol/L). The increase in the UC efflux was much more limited
      (1.4-fold) in the presence of the 53-nm APF/high-PC particles, but it was higher
      than that mediated by apo A-I. In addition, the efflux mediated by the synthetic
      peptide, in lipid-free or low-lipidated form, constituted the major part of that
      related to the full-length APF. Thus, all these particles are very active HDL
      components, able to act as cholesterol acceptors. Interestingly, we further
      showed a new anti-atherogenic property of APF as well as its metabolic importance
      and clinical relevance. By its involvement in the first step of the reverse
      cholesterol transport, APF could reduce the risk of cardiovascular disease.

PMID- 16092061
TI  - Familial massive tendon xanthomatosis with decreased high-density lipoprotein
      mediated cholesterol efflux.
AB  - We experienced a family with novel massive tendon xanthomatosis which can be
      excluded from known disease causing xanthomatosis. The proband was a 58-year-old
      man who had necrosis in his massive Achilles tendon xanthoma. Three of 5 brothers
      including him and his nephew had the same clinical phenotype. The systemic tendon
      xanthomatosis became apparent around 30 years of their age. The proband and his
      elder brother had mild elevations of serum total cholesterol level (251 and 228
      mg/dL, respectively). The low-density lipoprotein receptor activity of the
      proband's lymphocytes was normal. Neither plant sterol nor cholestanol level was
      increased in the proband's plasma. Magnetic resonance image of the proband's
      Achilles tendon demonstrated a massive expansion of the soft tissue with salami
      sausage-like appearance in his heels (50 mm in thickness). The physiological
      function of macrophages (MPhi) from the patients was investigated to clarify the
      mechanism for the formation of xanthomatosis. There was no significant difference
      in the uptake of oxidized low-density lipoprotein between the proband's MPhi and
      the control. High-density lipoprotein 3-mediated cholesterol efflux from the
      patients' MPhi (n = 2) was significantly reduced compared with the controls (n =
      3), whereas there was no difference in apolipoprotein (apo) A-I-mediated
      cholesterol efflux between the patients' MPhi and the controls. Furthermore,
      there was no reduction of the messenger RNA levels of ATP-binding cassette
      transporter 1 (ABCA1), which is involved in apo A-I-mediated cholesterol efflux,
      in the proband's MPhi compared with the control. The present study demonstrates
      that the mechanism for the formation of novel familial massive tendon
      xanthomatosis may be, at least in part, associated with decreased high-density
      lipoprotein 3, but not free apo A-I-mediated cholesterol efflux from MPhi in
      vivo.

PMID- 16092062
TI  - Relationship between blood lactate concentration and substrate utilization during
      exercise in type 2 diabetic postmenopausal women.
AB  - Increased blood lactate concentration and alterations of substrate utilization
      have been shown to be partly involved in development of insulin resistance in
      obese and type 2 diabetic patients. As blood represents the first great
      distribution space and participates to lactate exchange in whole body, we
      investigated lactate transport in red blood cells at rest and the potential
      relationships between elevated blood lactate and substrate utilization in 7 obese
      controls and 7 obese type 2 diabetic postmenopausal women during an incremental
      exercise test. Blood samples were collected at rest, 30%, 50%, and 60% of maximal
      power and at 8 and 20 minutes of recovery time. Baseline lactatemia and its
      increase during exercise were higher in the diabetic group (P < .05). We found a
      negative correlation between basal and 30% maximal power lactatemia and 2 indexes
      of substrate utilization (crossover point: r = -0.79, r = -0.82 and maximal lipid
      oxidation point: r = -0.83, r = -0.80; P < .05) in diabetic group only.
      Furthermore, there were positive correlations between the affinity constant,
      maximal velocity transport, and basal lactate level in diabetic subjects (r =
      0.91 and r = 0.73, respectively; P < .05). These results show that the elevation
      of blood lactate is associated with a greater carbohydrate oxidation in type 2
      diabetes, but the mechanisms underlying the alteration of substrate utilization
      need to be clarified. Furthermore, increased lactate levels cannot be explained
      by alterations of lactate transport in red blood cells, but it could affect
      monocarboxylate transporter 1 properties.

PMID- 16092063
TI  - Ornithine alpha-ketoglutarate metabolism in the healthy rat in the postabsorptive
      state.
AB  - To gain further insight into the ability of ornithine alpha-ketoglutarate (OKG)
      to generate key metabolites, the aim of this work was to study the short-term
      metabolism, that is, 1 hour after administration, of OKG in plasma and tissues.
      Particular attention was paid to keto acids (alpha-ketoglutarate and branched
      chain keto acids). Young (3 weeks old) male Wistar rats in the postabsorptive
      state received either 1.5 g/kg of monohydrated OKG (OKG group, n = 8) diluted in
      distilled water or an equivalent volume of saline solution at 0.9% (control
      group, n = 8) by gavage and were killed 1 hour later. Plasma, liver, jejunal and
      ileal mucosa, and the extensor digitorum longus muscle were removed to analyze
      amino and keto acid contents. Major metabolites detected after OKG ingestion
      (ornithine [ORN], alpha-ketoglutarate, proline and glutamate; OKG vs control, P <
      .05) and the absence of increased arginine (and even a decrease in jejunum and
      muscle) and citrulline levels suggested that ORN was mainly metabolized by the
      ORN aminotransferase pathway. In addition, significantly decreased plasma
      branched-chain keto acids and increased hepatic branched-chain amino acids (OKG
      vs control, P < .05) were observed upon OKG ingestion. Finally, glutamine
      accumulation restricted to the intestine, as evidenced in this short-term study,
      suggests that the effects of OKG on glutamine pools in other tissues in various
      pathological states after several days of treatment, as observed in previous
      studies, may be related to a long-term induction of glutamine synthetase.

PMID- 16092064
TI  - Metabolic syndrome at follow-up in women with and without gestational diabetes
      mellitus in index pregnancy.
AB  - We prospectively studied 262 women with prior gestational diabetes mellitus (GDM)
      and 66 control women to compare their prevalence of metabolic syndrome and its
      relationship with insulin secretion and sensitivity. A 75-g oral glucose
      tolerance test was scheduled 5 years after delivery along with lipid profile,
      anthropometrics, and blood pressure measurement. Metabolic syndrome was defined
      according to the National Cholesterol Education Program 2001, and insulin
      sensitivity and secretion were estimated with the homeostasis model assessment.
      Women with prior GDM had similar insulin sensitivity and lower insulin secretion
      than control women. In comparison with control women, women with prior GDM had
      higher blood pressure, waist circumference, very low-density lipoprotein
      cholesterol, and oral glucose tolerance test blood glucose values but, with the
      exception of fasting hyperglycemia, did not have an increased prevalence of
      metabolic syndrome or its components. The multivariate prediction of metabolic
      syndrome and its components was similar with age and current homeostasis model
      assessment-insulin secretion and resistance indexes or with age, obesity, and
      GDM. The main predictor was current insulin resistance in the first case and
      obesity in the second, obesity being the best predictor overall. We conclude that
      in our population and at midterm follow-up, women with prior GDM have a decreased
      insulin secretion and display a higher prevalence of fasting hyperglycemia but
      not the full-blown picture of metabolic syndrome. Obesity, a surrogate index of
      insulin resistance, is the best predictor of metabolic syndrome at follow-up.

PMID- 16092066
TI  - Biosynthetic (14)C-labelling of xanthohumol in hop cones.
AB  - Xanthohumol (Xn) has well-established chemopreventive potential in vitro. In
      order to carry out in vivo bioavailability and tissue distribution studies,( 14)C
      labelled Xn was produced by biolabelling. Supplying hop sprouts with 5 mCi [U
      (14)C]glucose led to incorporation of (14)C into Xn. Delivering the radioactive
      precursor at once resulted in Xn with a specific activity of 318 microCi.mmol(
      1); if however the amount was supplied in aliquots over 4 days a specific
      activity of only 53.1 microCi.mmol(-1) Xn was obtained.

PMID- 16092067
TI  - Xanthohumol does not affect the composition of rat intestinal microbiota.
AB  - Xanthohumol (XN), a prenylated chalcone, has been proposed to have beneficial
      effects on human health, including antimicrobial activity. To clarify whether the
      exposure to XN has an impact on the composition of the intestinal microbiota, 100
      mg XN/kg body weight was given daily to rats for 4 wk. Diversity of the fecal
      microbial community was analyzed using PCR-DGGE. Although intact XN was detected
      in the feces of the rats at a concentration of up to 2.3 mg/g fecal dry weight,
      major shifts in the PCR-DGGE patterns in response to this flavonoid were not
      observed. The similarity index decreased slightly from 70 to 62% for the XN
      treated rats and from 71 to 63% for the untreated animals. Thus, changes in the
      rat fecal microbiota observed in the course of the XN application are most likely
      due to intraindividual variability. However, the water content of the feces
      increased significantly during the XN treatment period.

PMID- 16092068
TI  - Xanthohumol stimulates iodide uptake in rat thyroid-derived FRTL-5 cells.
AB  - Sodium-iodide-symporter (NIS), an integral plasma membrane glycoprotein, mediates
      the sodium-dependent active uptake of iodide (I(-)) into the thyroid gland, which
      is a fundamental step in thyroid hormone synthesis. In this work, we analyzed the
      influence of xanthohumol (XN), a prenylated chalcone from hops (Humulus lupulus
      L.), on the I(-) uptake in a cell culture model of normal, nontransformed rat
      thyrocytes (FRTL-5). Acute treatment with nanomolar concentrations of XN does not
      influence I(-) uptake, but after 2 and 3-days of XN stimulation an increase in I(
      ) uptake was observed; I(-) uptake was maximally increased by 50% compared to
      control after 3-days of XN stimulation at 1 nM. A clear time-dependent
      stimulation was observed which showed no marked concentration relationship,
      however. To investigate whether expression of NIS mRNA is also increased, we grew
      FRTL-5 cells for 3-days in a medium containing increasing concentrations of XN
      (0.1 nM-1 muM). Northern blot analysis showed no difference in NIS mRNA
      transcript levels between control cells and those treated with different
      concentrations of XN. This study revealed that nanomolar concentrations of XN, a
      unique compound with anticancer properties, exert stimulating effects on
      radioiodide uptake. In contrast to many other plant-derived phenolic secondary
      metabolites such as (iso-)flavonoids, which inhibit I(-) uptake, XN might be an
      interesting candidate for more efficient radioiodide therapy of thyroid and
      perhaps other cancer expressing NIS such as breast cancer.

PMID- 16092069
TI  - In vitro phase II metabolism of xanthohumol by human UDP-glucuronosyltransferases
      and sulfotransferases.
AB  - Xanthohumol (XN) is the principal prenylated flavonoid of the hop plant and has
      recently gained considerable interest due to its potential cancer-chemopreventive
      effects. However, the metabolism of XN has not yet been investigated in detail.
      Therefore, we studied the in vitro phase II metabolism of XN using nine human
      recombinant UDP-glucuronosyltransferases (UGT) and five sulfotransferases (SULT).
      The identification of the metabolites formed was elucidated using HPLC with diode
      array detection as well as HPLC/API-ES MS. XN was efficiently glucuronidated by
      UGT 1 A 8, 1 A 9, and 1 A 10; further important UGTs were UGT 1 A 1, 1 A 7, and 2
      B 7. With respect to the sulfation reaction, SULT 1 A 1*2, 1 A 2, and 1 E 1 were
      the most active SULT forms. UGT 1 A 3, 1 A 4, and 1 A 6 as well as SULT 1 A 3 and
      2 A 1 were of minor importance for the conjugation of XN. Three mono-glucuronides
      as well as three mono-sulfates were identified. Considering the tissue
      distribution of the tested UGT and SULT enzyme forms, these findings suggest a
      prominent role for the glucuronidation and sulfation of XN in the liver as well
      as in the gastrointestinal tract.

PMID- 16092070
TI  - A safety study of oral xanthohumol administration and its influence on fertility
      in Sprague Dawley rats.
AB  - Xanthohumol (XN) is a prenylated chalcone, which has been shown to possess a
      broad range of potential cancer preventive and additional biological activities.
      In the present study, we have determined the subchronic 4-wk toxicity of XN and
      monitored its influence on fertility and development of offspring in two
      fertility studies. Four-week-old female Sprague Dawley (SD) rats were treated
      with 0.5% XN in the diet or with 1,000 mg XN/kg body weight (b.w.) per day by
      gavage for 28 days. No remarkable treatment-related changes in general appearance
      and b.w. occurred during the study. After autopsy, liver, kidney, lung, heart,
      stomach, and spleen were examined macroscopically and histopathologically.
      Relative liver weights of animals in both treatment groups were significantly
      reduced by 30--40% in comparison with the control group, indicating weak
      hepatotoxicity. Also, mammary glands of treated rats appeared less developed
      compared to the controls. Consequently, we investigated the influence of XN on
      rat reproduction. In two fertility studies, XN (100 mg/kg b.w. per day), given
      either for 4 wk prior to or during mating, gestation, and nursing, did not cause
      any adverse effects on female reproduction and the development of offspring.
      Noteworthy, treatment of male rats prior to mating significantly (p=0.027)
      increased the sex ratio of male to female offspring. Overall, lifelong treatment
      at a daily dose of 100 mg/kg b.w. in a two-generation study did not affect the
      development of SD rats.

PMID- 16092071
TI  - Broad spectrum anti-infective potential of xanthohumol from hop (Humulus lupulus
      L.) in comparison with activities of other hop constituents and xanthohumol
      metabolites.
AB  - This review summarizes the capacity of xanthohumol (XN) in comparison with
      additional hop constituents and metabolites to act as an antiinfective agent
      against microorganisms including bacteria, viruses, fungi and malarial protozoa.
      XN was shown to inhibit the Gram-positive bacteria Staphylococcus aureus and
      Streptococcus mutans. Antiviral activity was demonstrated against bovine viral
      diarrhea virus, cytomegalovirus, herpes simplex virus type 1 and 2 and human
      immunodeficiency virus 1. Inhibition of two Trichophyton spp. was indicative of
      antifungal activity. Finally, XN potently inhibited the replication of Plasmodium
      falciparum, the causative agent of malaria. This effect was linked to the
      inhibition of glutathione-mediated degradation and detoxification of haemin, a by
      product of the parasitic digestion of haemoglobin. Overall, these activities
      further contribute to the broad spectrum of biological effects observed with XN.

PMID- 16092073
TI  - Parkinson's disease: a broken nosology.
AB  - Parkinson's disease (PD) is a clinical diagnosis. We argue here that if we are to
      make progress in understanding its underlying pathogenesis, there is a need to
      have a pathological definition of disease that includes the presence of Lewy
      bodies and nigral loss in the ventrolateral tier of the pars compacta of the
      substantia nigra. Using such a definition, there is only one certain and known
      cause: mutations in the alpha-synuclein gene. However, the phenotype of this one
      known cause is broader than PD and encompasses Lewy body dementia.

PMID- 16092074
TI  - How to diagnose multiple system atrophy.
AB  - The diagnosis of multiple system atrophy (MSA) in life remains entirely clinical.
      Consensus diagnostic criteria have been developed, but their use does not
      particularly render a diagnosis of MSA more accurate than are clinicians'
      diagnoses. Some patients may not fulfill the stipulated core diagnostic criteria,
      yet display many so-called red flags pointing toward MSA. The additional
      usefulness of these red flags and of a variety of investigations currently is
      being investigated, with a view to some of them being incorporated in future sets
      of diagnostic criteria.

PMID- 16092075
TI  - How to diagnose dementia with Lewy bodies: state of the art.
AB  - Dementia with Lewy bodies (DLB) is the second most common cause of
      neurodegenerative dementia in older people that has only been recognized in the
      past decade and that remains widely underdiagnosed. At postmortem examination,
      affected patients show numerous alpha-synuclein-positive Lewy bodies (LB) in many
      parts of the cerebral cortex, particularly neocortical and limbic areas in
      addition to the nigral LB degeneration characteristic of Parkinson's disease
      (PD). Clinical presentation, unlike PD, is with progressive cognitive decline
      with particular deficits of visuospatial ability as well as frontal executive
      function accompanied by usually only mildly to moderately severe parkinsonism,
      which is often akineto-rigid without the classical parkinsonian rest-tremor.
      Further accompanying features include spontaneous recurrent visual hallucinations
      and conspicuous fluctuations in alertness and cognitive performance. The two main
      differential diagnoses are Alzheimer's disease (AD) and Parkinson's disease
      dementia (PDD). To improve the differential diagnosis of DLB, consensus criteria
      have been developed that establish possible and probable levels of clinical
      diagnostic accuracy. Generally, their sensitivity is variable and low but their
      specificity is high. Current consensus is to restrict a diagnosis of DLB only to
      patients with parkinsonism who develop dementia within 12 months of the onset of
      motor symptoms. Using operationalized criteria, DLB can be diagnosed clinically
      with an accuracy similar to that achieved for AD or PD. Ancillary investigations,
      particularly neuroimaging, can aid in differential diagnosis. We review the
      present state of the best practice in the clinical diagnosis of DLB. Future
      modifications of diagnostic criteria would ideally include the full range of
      clinical presentations that can be associated with LB disease.

PMID- 16092076
TI  - Progressive supranuclear palsy and corticobasal degeneration: lumping versus
      splitting.
AB  - Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are both
      sporadic disorders with tau pathology. Criteria have been defined that in most
      instances allow for adequate diagnosis of the two disorders both clinically and
      neuropathologically; however, overlap is not uncommon. For example, patients with
      PSP may present with severe unilateral apraxia and supranuclear gaze palsy can
      occur in CBD. Pathological overlap also occurs and pathologically "mixed" cases
      are encountered. Common to both these two tauopathies is that isoforms of four
      repeat tau due to splicing of exon 10 define the tau filamentous aggregates. This
      is in contrast to other tau disorders such as Pick's with three-repeat tau
      aggregates. Additional evidence for a causal link between PSP and CBD is the
      finding that both disorders are homozygous for the H1 tau haplotype. Furthermore,
      in some families with parkinsonism linked to defined mutations of the tau gene
      (FTDP-17), involved relatives have presented with PSP whereas others with the CBD
      phenotype. Although PSP and CBD frequently can be clearly separated clinically
      and pathologically, the degree of clinicopathological and genetic overlap is
      important and suggests that they represent different phenotypes of the same
      disorder, with differences occurring perhaps in relation to different genetic
      background. That PSP and CBD are distinct nosological entities occurring in
      patients with similar genetic predisposition cannot be ruled out.

PMID- 16092077
TI  - A new threshold dose-response model including random effects for data from
      developmental toxicity studies.
AB  - Usually, in teratological dose finding studies, there are not only threshold
      effects but also extra variations that cannot be accounted for by the beta
      binomial model alone. The beta-binomial model assumes correlation between fetuses
      in the same litter. The general random effect threshold (RE) model allows the
      additional variability that arises due to correlation and between litter
      variability to be modeled, in combination with threshold in the model. The goal
      of this research was to investigate a threshold dose-response model with random
      effects (RE) to model the variability that exists between litters of animals in
      studies of toxic agents. Data from a developmental toxicity study of a toxic
      agent were analysed, using the proposed RE threshold dose-response model, which
      is an extension of logit in form. Also, an approximate likelihood function was
      used to derive parameter estimates from this model, and tests were performed to
      determine the significance of the model parameters, in particular, the RE
      parameter. A simulation study was conducted to assess the performance of the RE
      threshold model in estimating the model parameters.

PMID- 16092078
TI  - Effective bisquaternary reactivators of tabun-inhibited AChE.
AB  - Two cholinesterase reactivators (K074 and K075) were synthesized and their
      reactivation efficacy against tabun-inhibited acetylcholinesterase of the rat
      brain was tested in vitro. Comparing this efficacy showed that commonly used
      oximes (pralidoxim, obidoxime and HI-6) were practically without reactivation
      potency. On the other hand, oximes K074, K075 and trimedoxime were satisfactorily
      effective. Moreover, K-oximes reactivated tabun-inhibited AChE at lower
      concentration (10(-4) and 10(-3) m) in comparison with trimedoxime (10(-3) and
      10(-2) m). Thus, K-oximes can be considered as the most effective reactivators of
      tabun-inhibited AChE at present.

PMID- 16092079
TI  - Effect of binge cocaine treatment on hindlimb vascular function.
AB  - Chronic cocaine abuse is known to cause endothelial dysfunction and
      atherosclerosis. The present study investigated the effect of binge cocaine
      treatment, a model for chronic cocaine abuse, on the blood flow responses to the
      adrenergic agonists norepinephrine, phenylephrine and isoproterenol, the
      endothelium-dependent vasodilator acetylcholine, and the endothelium independent
      vasodilator sodium nitroprusside (SNP) in the hindlimb vascular bed of male
      Sprague Dawley rats. Rats received either single binge or double binge treatment.
      Each binge treatment consisted of three doses of cocaine (30 mg kg(-1) i.p.) for
      3 days. For double binge treatment, there was a 4 day recovery period between the
      binges. At the end of the treatment the rats were anesthetized and agonists were
      administered into the right hindlimb circulation through a catheter in the left
      iliac artery and blood flow responses were measured with a flow probe around the
      right iliac artery. Rats receiving double cocaine binges showed a significant
      decrease in the magnitude and duration of the blood flow response to
      norepinephrine and a decrease in the duration of the blood flow response to
      phenylephrine, isoproterenol and acetylcholine when compared with saline
      controls. The blood flow response to SNP was not changed. Total plasma nitrate
      nitrite levels were significantly reduced and big endothelin levels were
      significantly increased in rats receiving double cocaine binges. This study
      demonstrates that binge cocaine treatment can alter endothelial function, while
      not changing smooth muscle function, and impairs the adrenergic pathway.

PMID- 16092080
TI  - Immediate post-dosing paralysis following severe soman and VX toxicosis in guinea
      pigs.
AB  - There have been numerous studies of the central nervous system (CNS) involvement
      in organophosphate (OP) poisoning showing status epilepticus and/or
      'electrographic seizures'. Brain damage has been demonstrated as 'neuronal
      necrosis' primarily in the cortex, thalamus and hippocampus. To the authors'
      knowledge there have been no reports of partial/total paralysis following close
      upon OP exposure although delayed paralysis has been reported. This report
      summarizes the immediate, OP induced paralytic events recorded in guinea pigs
      during development of the Canadian reactive skin decontaminant lotion (RSDL). As
      part of the development work, supra-lethal cutaneous doses of OP were applied to
      large numbers of guinea pigs followed by decontamination with the RSDL or
      predecessor lotions and solvents. Soman (pinacolyl methylphosphonofluoridate; GD)
      challenges were applied to 1277 animals and S-(2-diisopropyl-aminoethyl)
      methylphosphorothiolate (VX) challenges to 108. The classic sequence of clinical
      signs--ptyalism, tremors, fasciculations, convulsions, apnea and flaccid
      paralysis before death--was seen in the 658 animals that died and in many of the
      survivors. Eighty-four of 688 survivors of GD and 4 of 39 survivors of VX showed
      random paralysis of various distal regions following recovery from an insult
      which produced convulsions and/or flaccid paralysis. Because the experiments were
      designed to assess the decontamination procedures, there were no apparent
      relationships between the amounts of OP applied and the sequellae recorded. The
      observations of paralysis were also incidental to the prime focus of the
      experiments. Because of this, only ten animals paralysed following GD exposure
      were examined for histological effects. The pathologist diagnosed
      'encephalomalacia' and 'focal necrotic lesions' in the cerebral cortex and 'focal
      necrotic lesions' in one spinal cord. Of the 84 guinea pigs paralysed after GD
      challenge, one was not decontaminated and the decontaminants used on the
      remainder were sufficiently varied that there appeared to be no relationship
      between the type of decontaminant and the resulting paralysis.

PMID- 16092081
TI  - Histopathological effects of Thiodan on the freshwater snail, Galba truncatula
      (gastropoda, pulmonata).
AB  - Histopathological alterations in three tissues, namely, digestive gland, foot and
      mantle of the freshwater snail Galba truncatula induced by Thiodan 35 EC, a
      commercial preparation of endosulfan, were studied in the laboratory. The snails
      were exposed to five sublethal concentrations of Thiodan, two of them higher
      concentrations at 0.33% and 0.65% in glass jars for short-term exposure (96 h)
      and three of them lower concentrations at 0.08%, 0.16% and 0.27% for long-term
      exposure (10, 20 and 30 days). Thiodan caused significant histopathological
      changes in the tissues of the snail, irrespective of the concentration of the
      pesticide and its exposure period. The histopathological changes included
      accumulation of amoebocytes in the hemolymphatic spaces between the tubules of
      the digestive gland, exudation in the lumen of tubules, expansion of
      hemolymphatic spaces between the tubules and increase of vacuolation and necrotic
      changes in the digestive cells. Disruption of columnar muscle fibers and
      alteration of epithelial layers were detected in the foot and mantle of the
      treated specimens. The number and size of mucous and protein cells in the foot
      and mantle also changed.

PMID- 16092082
TI  - Pro-oxidative vs antioxidative properties of ascorbic acid in chromium(VI)
      induced damage: an in vivo and in vitro approach.
AB  - The effect of antioxidant ascorbic acid (vitamin C) pretreatment on chromium(VI)
      induced damage was investigated using the yeast Saccharomyces cerevisiae as a
      model organism. The objective of this study was to pretreat yeast cells with the
      antioxidant ascorbic acid in an effort to increase cell tolerance against
      reactive chromium intermediates and reactive oxygen species formed during
      chromium(VI) reduction. Intracellular oxidation was estimated using the
      fluorescence indicators dihidro-2,7-dichlorofluorescein, dihydroethidium and
      dihydrorhodamine 123. The role of ascorbic acid pretreatment on chromium(VI)
      toxicity was determined by measuring mitotic gene conversion, reverse mutations,
      8-OHdG, hydroxyl radical, superoxide anion and chromium(V) formation. The
      chromium content in the biomass was determined by flame atomic absorption
      spectrometry. In the absence of chromium, ascorbic acid effectively protected the
      cells against endogenous reactive oxygen species formed during normal cellular
      metabolism. In vitro measurements employing EPR and the results of supercoiled
      DNA cleavage revealed that the pro-oxidative action of ascorbic acid during
      Cr(VI) reduction was concentration-dependent and that harmful hydroxyl radical
      and Cr(V) had formed following Cr(VI) reduction. However, the in vivo results
      highlighted the important role of increased cytosol reduction capacity related to
      modification of Cr(V) formation, increased chromium accumulation, better
      scavenging ability of superoxide anions and hydrogen peroxide, and consequently
      decreased cytotoxicity and genotoxicity in ascorbic acid pretreated cells.
      Ascorbic acid influenced Cr(VI) toxicity both as a reducing agent, by decreasing
      Cr(V) persistence, and as an antioxidant, by decreasing intracellular superoxide
      anion and hydrogen peroxide formation and by quenching free radicals formed
      during Cr(VI) to Cr(III) reduction. Increased 8-OHdG and decreased reduced
      glutathione in ascorbic acid-treated cells might induce an endogenous antioxidant
      defense system and thus increase cell tolerance against subsequent Cr-induced
      stress.

PMID- 16092083
TI  - Up-and-down procedure (UDP) determinations of acute oral toxicity of nitroso
      degradation products of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).
AB  - Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a widely used military explosive
      and soil and ground water contaminant of munitions manufacturing and artillery
      training sites, undergoes microbial nitroreductase metabolism to hexahydro-1
      nitroso-3,5-dinitro-1,3,5-triazine (MNX), hexahydro-1,3-dinitroso-5-nitro-1,3,5
      triazine (DNX), and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX). Human
      occupational and accidental exposures to RDX, as well as acute oral exposures in
      rats, result in seizures, but little is known about the toxicity of the RDX
      degradation products. The main objective of the present study was to determine
      the oral LD50 of the most potent RDX N-nitroso product in female Sprague-Dawley
      rats using the recently validated up-and-down procedure (UDP). With only 26 rats,
      MNX was identified as the most potent metabolite and a maximum likelihood
      estimate of 187 mg kg(-1) (95% confidence interval 118-491 mg kg(-1)) for its
      LD50 was established and found equivalent to that of RDX determined with the same
      protocol. CNS toxicity, manifested as forelimb clonic seizures progressing to
      generalized clonic-tonic seizures, was the critical adverse effect. Further,
      confirmation of the UDP LD50 for MNX with a fixed-dose design enabled
      identification of 94 mg kg(-1) as the highest nonlethal dose. An ED50 of 57 mg
      kg(-1) was determined for neurotoxicity, while splenic hemosiderosis and
      decreased blood hematocrit and hemoglobin concentration occurred with a threshold
      at 94 mg kg(-1) in 14-day survivors. These studies, while providing new toxicity
      data necessary for the management of RDX-contaminated sites, illustrate the
      efficiency of the UDP for comparative acute toxicity determinations and its value
      in guiding further characterization of dose dependency of identified adverse
      effects.

PMID- 16092084
TI  - Serum levels of albumin, triglycerides, total protein and glucose in rats are
      altered after oral treatment with low doses of 13-cis-retinoic acid or all-trans
      retinoic acid.
AB  - Currently used to treat severe acne, 13-cis-retinoic acid (13-cis-RA) is under
      investigation for its anticancer effects as is the isomer, all-trans-retinoic
      acid (all-trans-RA). Here, the effects of oral 13-cis-RA or all-trans-RA
      treatment on serum chemistry, leptin and adiponectin levels were evaluated. Adult
      Sprague-Dawley rats were gavaged once daily for 7 consecutive days with 13-cis-RA
      (7.5 or 15 mg kg(-1)), all-trans-RA (10 or 15 mg kg(-1)) (n=24/sex/dose), or soy
      oil (n=16/sex) and blood was sampled 30-480 min after the last gavage. The body
      weight was unaffected; however, the liver/body weight ratios were increased by
      both doses of all-trans-RA. Sex differences were noted for levels of cholesterol,
      creatine, triglycerides, albumin, alanine aminotransferase and total protein.
      Both doses of all-trans-RA reduced albumin levels to approximately 90% of the
      control and total protein levels to approximately 93% of the control while
      substantially elevating triglyceride levels to approximately 66%-99% above the
      control. Additionally, triglyceride levels of the 15 mg kg(-1) 13-cis RA group
      were approximately 62% higher than the controls and total protein levels were
      approximately 5% less. Glucose levels were affected by sex and RA treatment in
      that males treated with 15 mg kg(-1) of 13-cis-RA or 10 mg kg(-1) all-trans-RA
      had lower (13%-19%) levels than the same-sex controls; however, females were not
      similarly affected. Neither 13-cis-RA nor all-trans-RA treatment had significant
      effects on the levels of blood urea nitrogen, aspartate amino transferase, leptin
      or adiponectin. On a mg kg(-1) basis, all-trans-RA was more potent than 13-cis
      RA. These results replicate previous findings of RA-induced increased
      triglyceride levels. Additionally, several new findings indicate there may be sex
      specific effects of RA treatment. Finally, neither treatment appeared to alter
      the typical diurnal cycles of these endpoints.

PMID- 16092085
TI  - Cytotoxic actions of palytoxin on aortic smooth muscle cells in culture.
AB  - Palytoxin (PTX), isolated from a zoanthid of the genus Palythoa, is the most
      potent marine toxin known. Intoxication by PTX leads to vasoconstriction,
      hemorrhage, ataxia, muscle weakness, ventricular fibrillation, pulmonary
      hypertension, ischemia and death. In this study, clonal A7r5 rat aortic smooth
      muscle cells were used to study the mechanism of PTX-mediated cytotoxicity. A7r5
      cells exposed to PTX for > or = 15 min exhibited surface granularities, vacuoles
      and rounding. These alterations culminated in a loss of viability as indicated by
      marked increases in the release of lactate dehydrogenase. Electrophysiological
      recording from A7r5 cells disclosed a profound membrane depolarization and an
      increase in conductance to Na+ and K+. PTX-mediated cytotoxicity could not be
      reversed by washout or by the addition of 10 microM verapamil but was antagonized
      by 100 microM ouabain or by removal of extracellular Na+ or Ca2+. In light of the
      involvement of vascular smooth muscle in PTX poisoning, A7r5 cells could serve as
      a useful model to test specific drugs for treatment of PTX intoxication.

PMID- 16092086
TI  - Expression of brush border enzymes in response to lead exposure in rat intestine.
AB  - The effect of feeding lead (50 mg kg(-1) body weight) daily for 7 days on the
      development of various brush border enzymes in the intestine has been studied.
      The activities of brush border sucrase (P < 0.001), lactase (P < 0.001), gamma
      glutamyl transpeptidase (P < 0.05) and leucine aminopeptidase were reduced (P <
      0.05), whereas the alkaline phosphatase level was augmented (P < 0.05) in lead
      fed rats compared with controls. Kinetic studies with sucrase revealed a low Vmax
      (0.224 in control and 0.160 units mg(-1) protein in lead exposed) with no change
      in Km (12.6-13.5 mM). Western blot analysis for alkaline phosphatase yielded
      intense staining of enzyme protein in lead fed rats compared with controls,
      however, the intensity of the antigen signal was reversed for sucrase under these
      conditions. These findings suggest that ingestion of lead may interfere with the
      crypt cell differentiation process thus affecting enzyme functions in the rat
      intestine.

PMID- 16092087
TI  - GB toxicity reassessed using newer techniques for estimation of human toxicity
      from animal inhalation toxicity data: new method for estimating acute human
      toxicity (GB).
AB  - Estimated human inhalation toxicity values for Sarin (GB) were calculated using a
      new two independent (concentration, exposure time), one dependent (toxic
      response), non-linear dose response (toxicity) model combined with re-evaluated
      allometric equations relating to animal and human respiration. Historical animal
      studies of GB toxicity containing both exposure and fractional animal response
      data were used to test the new process. The final data set contained 6621
      animals, 762 groups, 37 studies and 7 species. The toxicity of GB for each
      species was empirically related to exposure concentration (C; mg m(-3)) and
      exposure time (T; min) through the surface function Y = b0 + b1 Log10C + b2
      Log10T or Y = b0 + b2 Log10C(n)T where Y is the Normit, b0, b1 and b2 are
      constants and n is the 'toxic load exponent' (Normit is PROBIT - 5). Between
      exposure times of 0.17 and 30 min, the average value for n in seven species was
      1.35 +/- 0.15. The near parallel toxic load equations for each species and the
      linear relationship between minute volume/body weight ratio and the inhalation
      toxicity (LCt50) for GB were used to create a pseudo-human data set and then an
      exposure time/toxicity surface for the human. The calculated n for the human was
      1.40. The pseudo-human data had much more variability at low exposure times.
      Raising the lower exposure limit to 1 min, did not change the LCt50 but did
      result in lower variability. Raising the lower value to 2 min was
      counterproductive. Based on the toxic load model for 1-30 min exposures, the
      human GB toxicities (LCt01, LCt05, LCt50 and LCt95) for 70 kg humans breathing 15
      l min(-1) were estimated to be 11, 16, 36 and 83; 18, 25, 57 and 132 and 24, 34,
      79 and 182 mg x min m(-3) for 2, 10 and 30 min exposures, respectively. These
      values are recommended for general use for the total human population. The
      empirical relationships employed in the calculations may not be valid for
      exposure times >30 min.

PMID- 16092088
TI  - Grading of neuropathology in multiple system atrophy: proposal for a novel scale.
AB  - Multiple system atrophy (MSA), a sporadic progressive synucleinopathy of advanced
      age, is separated into two clinic opathological subtypes: MSA-P (striatonigral
      degeneration [SND]) with predominant parkinsonian features and MSA-C
      (olivopontocerebellar atrophy [OPCA]) with predominant cerebellar ataxia. We
      propose a novel morphological grading system for both subtypes to compare lesion
      intensities and their possible clinical validity. Forty-two autopsy cases of MSA
      were separated into four grades (SND 0-III and OPCA 0-III) based on
      semiquantitative assessment of neuronal loss, astrogliosis, and presence of alpha
      synuclein-positive glial cytoplasmic inclusions (GCI) in striatum, globus
      pallidus, substantia nigra, pontine basis, cerebellum, and inferior olives.
      Whereas a recent grading system restricted to SND reflected disease progression
      and dopa-responsiveness, there was considerable variation in the morphological
      combination between SND and OPCA, with only around half the cases with OPCA II
      (moderate) and III (severe) showing comparable grades of both types, whereas OPCA
      0 and I (no or little degeneration) was combined with all grades of SND. Twenty
      two cases showing OPCA 0 + SND II (n = 3), OPCA I + SND I-II (n = 11), and OPCA I
      + SND III (n = 8) were classified as pure or predominant SND, consistent with MSA
      P. Twenty cases showing OPCA II + SND II/III (n = 7) and OPCA III + SND III (n =
      13) were classified as predominant OPCA, consistent with MSA-C. In MSA-P, the
      mean age of onset was higher than it was in MSA-C (55.1 vs. 50.5 years), but the
      mean duration of illness was shorter in MSA-P (5.3 vs. 6.7 years). Presenting
      symptoms in MSA-P were mainly parkinsonism, whereas in MSA-C they were mainly
      gait disorders (14 vs. 1; P < 0.001). Among clinical key symptoms, parkinsonism
      was more frequent than were cerebellar signs in MSA-P; in MSA-C it was the
      reverse (P < 0.01), whereas other symptoms (autonomic/urinary failure) showed no
      differences. Parkinsonism was infrequent in MSA-C even when OPCA was associated
      with SND, suggesting a masking effect by cerebellar system involvement. High
      terminal Hoehn and Yahr stages were more frequent in MSA-P (P < 0.01), some with
      good-to-moderate initial levodopa (L-dopa) response. Although the proposed
      morphological grading of both MSA-P and -C correlates well with initial symptoms
      and clinical key features of both types, further prospective studies are required
      to validate the clinical utility of the proposed MSA grading scales for future
      intervention studies.

PMID- 16092089
TI  - Alpha-synuclein dysfunction in Lewy body diseases.
AB  - alpha-Synuclein belongs to a small group of natively unfolded proteins that can
      transiently bind to lipid membranes and acquire a partial alpha-helical
      conformation. Its relevance to Parkinson's disease (PD) is based on mutations
      found in familial cases of the disease and its presence in filaments of Lewy
      bodies (LB) and Lewy neurites (LN) in sporadic cases where it is packed in a beta
      sheet configuration. This structural plasticity of alpha-synuclein has raised the
      possibility that neurodegeneration may be a consequence of abnormal protein
      folding. The extent to which abnormal folding and aggregation of neuronal
      proteins is directly toxic to the cell, an inert biochemical marker of an
      underlying harmful metabolic defect, or a protective reaction remains to be seen.
      We review the function of alpha-synuclein and recent studies that have shed light
      on the mechanisms by which it aggregates.

PMID- 16092090
TI  - Tau gene mutations and their effects.
AB  - Tau is the major component of the intracellular filamentous deposits that define
      a number of neurodegenerative diseases, including the largely sporadic
      Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration,
      Pick's disease, and argyrophilic grain disease, as well as the inherited
      frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). For a
      long time, it was unclear whether the dysfunction of tau protein follows disease
      or whether disease follows the dysfunction of tau protein. The identification of
      mutations in Tau as the cause of FTDP-17 has resolved this issue. About half of
      the known mutations have their primary effect at the protein level, and they
      reduce the ability of tau protein to interact with microtubules and increase its
      propensity to assemble into abnormal filaments. The other mutations have their
      primary effect at the RNA level, thus perturbing the normal ratio of three-repeat
      to four-repeat tau isoforms. Where studied, this resulted in the relative
      overproduction of tau protein with four microtubule-binding repeats in brain.
      Several Tau mutations give rise to diseases that resemble progressive
      supranuclear palsy, corticobasal degeneration, or Pick's disease. Moreover, the
      H1 haplotype of Tau has been identified as a significant risk factor for
      progressive supranuclear palsy and corticobasal degeneration.

PMID- 16092091
TI  - In vitro models of multiple system atrophy.
AB  - alpha-Synuclein represents the major constituent of oligodendroglial cytoplasmic
      inclusions, the hallmark lesion of multiple system atrophy (MSA), a progressive
      disorder that is associated with selective degenerative cell loss in basal
      ganglia, cerebellum, brainstem, and spinal cord. The role of abnormal alpha
      synuclein aggregation in oligodendroglial cells is still obscure, in particular,
      whether alpha-synuclein might impair oligodendroglial and, secondarily, neuronal
      integrity of those cells in the diseased brain. In an attempt to answer some of
      these questions, we have developed an "in vitro model of MSA" by expressing the
      wild-type or C-terminally truncated form of alpha-synuclein in glial cell
      cultures. With this simplified system, we have demonstrated that alpha-synuclein
      significantly affects the survival of glia and its vulnerability to environmental
      stress, which might represent a major step in the pathogenesis of MSA.

PMID- 16092092
TI  - In vivo models of multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative
      disorder of unknown etiology clinically characterized by a combination of
      parkinsonian, pyramidal, and cerebellar signs. Levodopa-unresponsive parkinsonism
      is present in 80% of MSA cases, and this dominant clinical presentation (MSA-P)
      is associated with a combined degeneration of the substantia nigra pars compacta
      and the striatum in anatomically related areas. The limited knowledge of the
      pathophysiology of MSA and the lack of therapeutic strategies prompted the
      development of lesion models reproducing striatonigral degeneration, the
      substrate of levodopa-unresponsive parkinsonism in MSA-P. This method was carried
      out first in rats with two different stereotaxic strategies using either two
      neurotoxins ("double toxin-double lesion") or a single neurotoxin ("single toxin
      double lesion"). Double-lesioned rat models showed severe motor impairment
      compared to those with a single nigral or striatal lesion and helped to mimic
      different stages of the disease. Systemic models were also developed in mice and
      primates using the nigral toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) and the striatal toxin 3-nitropropionic (3-NP). In mice, although MPTP
      reduced the subsequent sensitivity to 3-NP in a sequential lesion, simultaneous
      nigral and striatal insults were shown to exacerbate striatal damage. MPTP
      treated monkeys displayed a significant worsening of parkinsonism and a loss of
      levodopa-responsiveness after the appearance of hindlimb dystonia and striatal
      lesion formation induced by subsequent 3-NP intoxication. The different species
      and intoxication paradigms used will be useful to investigate functional changes
      in substantia nigra and striatum and to define neuroprotective, neurorestorative,
      or symptomatic therapeutic strategies.

PMID- 16092093
TI  - Alpha-synuclein transgenic mice: relevance to multiple system atrophy.
AB  - (Oligodendro)glial cytoplasmic inclusions composed of the protein alpha-synuclein
      (alphaSYN) are the neuropathological hallmark lesions of multiple system atrophy
      (MSA). The recent generation of transgenic mouse models of oligodendroglial alpha
      synucleinopathy has enabled studies to investigate how alphaSYN causally
      contributes to MSA neuropathology. Moreover, human disease-specific pathological
      modifications of alphaSYN were recapitulated in transgenic mice, including
      insolubility, phosphorylation at serine-129, and ubiquitination. Thus, the
      transgenic mice will be useful tools to assess cellular risk factors, such as
      protein folding stress, protein kinase hyperactivity, and failure of the
      ubiquitin-proteasome system. Moreover, transgenic mice expressing a hyperactive
      alpha(1B)-adrenergic receptor mutant showed evidence of alphaSYN pathology in
      oligodendrocytes, adding dysregulated adrenergic neurotransmission to the list of
      potential risk factors of MSA. Finally, a double-transgenic mouse model
      expressing both alphaSYN and tau revealed synergistic fibrillization of these two
      proteins, providing an animal model for the not uncommon neuropathological
      finding of concomitant alpha-synucleinopathy and tauopathy within
      oligodendrocytes. Despite the progress made modeling MSA neuropathology in the
      transgenic mouse models, the molecular mechanism of how alphaSYN aggregation in
      oligodendrocytes causes neurodegeneration remains to be established. Moreover, it
      will be important to understand what defines the predilection sites most severely
      affected by striatonigral degeneration (MSA-P) and olivopontocerebellar atrophy
      (MSA-C), respectively.

PMID- 16092094
TI  - Therapeutic strategies in multiple system atrophy.
AB  - This review provides an update on therapeutic principles and their implications
      for practical management in multiple system atrophy (MSA), a sporadic
      neurodegenerative disorder characterized clinically by various combinations of
      dysautonomia, Parkinsonism, or cerebellar ataxia, often associated with other
      warning features (red flags), and pathologically by cell loss, gliosis, and glial
      cytoplasmic inclusions in selected multiple regions of the brain and spinal cord.
      Because of the small number of randomized controlled trials, the management of
      MSA is largely based on empirical or open-label evidence. Parkinsonism often
      shows a poor or unsustained response to chronic levodopa therapy, although more
      patients than previously recognized may experience an initial moderate-to-good
      dopaminergic response. There is no effective drug treatment for cerebellar
      ataxia. However, features of dysautonomia such as orthostatic hypotension,
      urinary retention or incontinence, constipation, and impotence, may often be
      relieved if recognized by the treating physician. Because no drug treatment
      consistently benefits patients with this disease in the long-term, palliative
      therapies are all the more important. Novel symptomatic and neuroprotective
      therapies are urgently required.

PMID- 16092095
TI  - Treatment of dementia with Lewy bodies and Parkinson's disease dementia.
AB  - Cognitive decline and dementia affect approximately 30% to 40% of patients with
      idiopathic Parkinson's disease during the course of their illness. PD-dementia
      (PDD) and dementia with Lewy bodies (DLB) are second to Alzheimer's disease in
      causing degenerative dementia in the elderly. The nosological distinction of the
      conditions has remained controversial because of broad clinical and pathological
      overlap. Treatment issues in both clinical settings are virtually identical.
      Treatment of Parkinsonism is often complicated by drug-induced psychosis and
      reduced levodopa responsiveness. Cognition, alertness, attention, as well as
      apathy or aggressive behavior have been shown to respond to treatment with
      cholinesterase inhibitors in randomized controlled trials both in DLB and PDD.
      Such treatment may also improve hallucinosis, but many patients will require add
      on treatment with atypical neuroleptics to control drug-induced psychotic
      reactions. Clozapine and quetiapine are the drugs most commonly used and,
      contrary to classic neuroleptics, risperidone or olanzapine do not seem to cause
      severe side effects according to published data.

PMID- 16092096
TI  - Treatment of progressive supranuclear palsy and corticobasal degeneration.
AB  - Success in treating patients with progressive supranuclear palsy and corticobasal
      degeneration remains exceedingly low. This finding probably relates to the
      widespread distribution of the pathological changes that account for the varied
      and complex spectrum of clinical manifestations. Dopaminergic drugs are regularly
      used for the parkinsonian features; however, these rarely result in more than
      modest benefit, and when better or sustained responses are obtained, as sometimes
      occurs in progressive supranuclear palsy, the clinical features are atypical and
      diagnosis is often delayed or not made in life. A variety of other treatments
      have been used in both disorders, sometimes directed at other specific features
      such as dystonia or myoclonus, and these treatments will be reviewed. Greater
      success in treating these disorders will require advances in our understanding of
      their cause(s) or the pathogenetic mechanisms underlying the neurodegenerative
      processes. The similarities in the molecular pathology of these four-repeat
      tauopathies suggests that important advances in the management of one will have a
      definite impact on the treatment of the other.

PMID- 16092097
TI  - Toward future therapies in progressive supranuclear palsy.
AB  - There is a stern therapeutic challenge for progressive supranuclear palsy (PSP)
      that has not yet been met. The lack of randomized, controlled trials and negative
      outcomes from the vast majority of studies make it impossible to set therapeutic
      standards, or to give clear recommendations. We review progress to date in this
      area and briefly consider future potential therapeutic strategies.

PMID- 16092098
TI  - Parkinsonism-dementia complex of Guam.
AB  - On Guam and in two other Pacific locales, indigenous residents and immigrants are
      prone to familial neurodegeneration that manifests as atypical parkinsonism,
      dementia, motor neuron disease, or a combination of these three phenotypes. This
      progressive and fatal disease of the Mariana islands, the Kii peninsula of Japan,
      and the coastal plain of West New Guinea is similar and the pathological features
      have close affiliation with universal tauopathies, including progressive
      supranuclear palsy, Alzheimer's disease, and amyotrophic lateral sclerosis. The
      Chamorros of Guam call the disease lytico-bodig, and neuroscientists refer to it
      as the amyotrophic lateral sclerosis/Parkinsonism-dementia complex. During recent
      decades, its prevalence has declined progressively, and the age at onset has
      steadily increased. In 2004, motor neuron disease, once 100 times more common
      than elsewhere is rare, atypical parkinsonism is declining, and only dementia
      remains unusually common in elderly females. The cause of this obscure malady
      remains uncertain, despite 60 years of international research, but its ending
      implicates environmental influences rather than genetic predisposition.

PMID- 16092099
TI  - Atypical parkinsonism of Japan: amyotrophic lateral sclerosis-parkinsonism
      dementia complex of the Kii peninsula of Japan (Muro disease): an update.
AB  - An update of the endemic parkinsonism-dementia complex (PDC) frequently
      associated with amyotrophic lateral sclerosis (ALS) in the high prevalence ALS
      focus of the Kii peninsula of Japan is presented. The initial symptom was
      parkinsonian gait or hypobulia/amnesia, which was followed by akinesia, rigidity,
      occasional tremor, bradyphrenia, abulia and amnesia, and finally by akinetic
      mutism. In several years, most of the patients developed ALS symptoms such as
      muscle atrophy, bulbar palsy, and upper motor neuron signs. Magnetic resonance
      imaging and computed tomography of the brain showed marked atrophy of the
      temporal and frontal lobes and the cerebral blood flow reduction on single-photon
      emission computed tomography. Marked loss of nerve cells associated with abundant
      neurofibrillar tangles (NFTs) in the entire central nervous system, most
      predominantly in the brainstem and temporal lobe was characteristic. Concomitant
      ALS pathology involving the upper and lower motor neurons was common, and senile
      plaques were absent in most cases. NFTs consisted of twisted tubules on electron
      microscopy. Western blot of tau protein showed three bands consisting of six tau
      isoforms, similar to those of Alzheimer's disease. A family history of ALS/PDC
      was recorded in more than 70% of patients, but no abnormal mutation or
      polymorphism was found in the genes of SOD1, tau, and apolipoprotein E. Familial
      nature and continuing morbidity of Kii ALS/PDC suggest that genetic factors may
      be more likely in its pathogenesis.

PMID- 16092100
TI  - Atypical unclassifiable parkinsonism on Guadeloupe: an environmental toxic
      hypothesis.
AB  - We characterize the clinical features of Parkinson's syndrome on Guadeloupe and
      describe possible environmental causes. Consecutive patients who were referred to
      the University Hospital at Pointe a Pitre with parkinsonism from September 1996
      to May 2002 were included. All cases were examined in a standardized manner by a
      neurologist with a special interest in movement disorders and independently by 3
      external movement disorders specialists, using standard operational clinical
      diagnostic criteria. The subjects were 265 patients with Parkinson's syndrome
      living on Guadeloupe, four fifths of whom had been referred by primary care
      physicians and one fifth by neurologists. The levodopa response was assessed
      after a minimum period of 1 month of continuous treatment. All patients had brain
      computed tomography or brain magnetic resonance imaging scans and detailed
      neuropsychological examinations. Of 265 patients, only 66 were classified as
      Parkinson's disease, whereas 58 fulfilled the National Institute of Neurological
      Disorders and Stroke (NINDS) and Society for Progressive Supranuclear Palsy
      (SPSP) criteria for progressive supranuclear palsy, 100 had unclassifiable
      parkinsonism, characterized by dopa-unresponsiveness, marked axial rigidity,
      relative symmetry of parkinsonian features, early dysarthria, and frontolimbic
      cognitive impairment. Within this group, early postural instability, dysarthria,
      a frontal behavior disorder, cortical or subcortical atrophy, pyramidal signs,
      axial rigidity, and family history of neurodegenerative disorders were associated
      with poorer prognosis. A very large number of unclassifiable cases of atypical
      parkinsonism that do not fulfill operational criteria for Parkinson's disease or
      other defined motor neurodegenerations has been observed on Guadeloupe. Most
      patients closely resemble descriptions of bodig from Guam. In both geographic
      isolates, an environmental cause has been discussed. Annonaceae fruits and herbal
      teas are consumed on both islands. These plants contain several neurotoxins,
      particularly acetogenins, which induce dopaminergic neuron loss in animals.
      Neuronal death involves cholinergic and dopaminergic cells of the substantia
      nigra and GABAergic neurons of the striatum, associated with microglial
      proliferation. The development of atypical parkinsonism in Guadeloupe and
      probably elsewhere, could result from synergistic toxicity, but acetogenins are
      probably the most potent neurotoxin, acting as mitochondrial complex I inhibitor.

PMID- 16092101
TI  - On the decline and etiology of high-incidence motor system disease in West Papua
      (southwest New Guinea).
AB  - The etiology of a high-incidence focus of amyotrophic lateral sclerosis and
      parkinsonism-dementia (ALS/P-D) in south West Papua (Irian Jaya, Indonesia),
      first described in the 1960s and 1970s, has been attributed to mineral
      deficiencies, hyperparathyroidism, and metal neurotoxicity arising from reliance
      on drinking water obtained from springs and shallow wells. More recent visits
      (1987 and 1990) to the south West Papua focus of neurodegenerative disease cast
      doubt on this explanation by revealing changes in disease prevalence in
      communities with an unchanged water supply. These communities have experienced a
      dramatic decline in ALS and a reversal in the relative prevalence of ALS and
      parkinsonism. The extrapyramidal disorder can be distinguished from Parkinson
      disease by pyramidal features (and dementia) reminiscent of Guam P-D. Topical use
      of cycad seed (termed kurru) gametophyte to treat large skin lesions is advanced
      as a plausible but unproven etiologic factor. Medicinal use of untreated cycad
      seed (Cycas sp.) has also been linked with ALS foci in Japan (oral use) and Guam
      (topical use), with the additional consumption on Guam of food items prepared
      from Cycas sp. seed or animals that consume cycad seed components.

PMID- 16092102
TI  - Cramer-Rao bounds for three-point decomposition of water and fat.
AB  - The noise analysis for three-point decomposition of water and fat was extended to
      account for the uncertainty in the field map. This generalization leads to a
      nonlinear estimation problem. The Cramer-Rao bound (CRB) was used to study the
      variance of the estimates of the magnitude, phase, and field map by computing the
      maximum effective number of signals averaged (NSA) for any choice of echo time
      shifts. The analysis shows that the noise properties of the reconstructed
      magnitude, phase, and field map depend not only on the choice of echo time shifts
      but also on the amount of fat and water in each voxel and their alignment at the
      echo. The choice of echo time shifts for spin-echo, spoiled gradient echo, and
      steady-state free precession imaging techniques were optimized using the CRB. The
      noise analysis for the magnitude explains rough interfaces seen clinically in the
      boundary of fat and water with source images obtained symmetrically about the
      spin-echo. It also provides a solution by choosing appropriate echo time shifts (
      pi/6+pik, pi/2+pik, 7pi/6+pik), with k an integer. With this choice of echo time
      shifts it is possible to achieve the maximum NSA uniformly across all fat:water
      ratios. The optimization is also carried out for the estimation of phase and
      field map. These theoretical results were verified using Monte Carlo simulations
      with a newly developed nonlinear least-squares reconstruction algorithm that
      achieves the CRB.

PMID- 16092103
TI  - Iterative decomposition of water and fat with echo asymmetry and least-squares
      estimation (IDEAL): application with fast spin-echo imaging.
AB  - Chemical shift based methods are often used to achieve uniform water-fat
      separation that is insensitive to Bo inhomogeneities. Many spin-echo (SE) or fast
      SE (FSE) approaches acquire three echoes shifted symmetrically about the SE,
      creating time-dependent phase shifts caused by water-fat chemical shift. This
      work demonstrates that symmetrically acquired echoes cause artifacts that degrade
      image quality. According to theory, the noise performance of any water-fat
      separation method is dependent on the proportion of water and fat within a voxel,
      and the position of echoes relative to the SE. To address this problem, we
      propose a method termed "iterative decomposition of water and fat with echo
      asymmetric and least-squares estimation" (IDEAL). This technique combines
      asymmetrically acquired echoes with an iterative least-squares decomposition
      algorithm to maximize noise performance. Theoretical calculations predict that
      the optimal echo combination occurs when the relative phase of the echoes is
      separated by 2pi/3, with the middle echo centered at pi/2+pik (k=any integer),
      i.e., (-pi/6+pik, pi/2+pik, 7pi/6+pik). Only with these echo combinations can
      noise performance reach the maximum possible and be independent of the proportion
      of water and fat. Close agreement between theoretical and experimental results
      obtained from an oil-water phantom was observed, demonstrating that the iterative
      least-squares decomposition method is an efficient estimator.

PMID- 16092104
TI  - Developmental toxicity study with triethylene glycol given by gavage to CD rats
      and CD-1 mice.
AB  - Triethylene glycol (TEG) is a liquid industrial chemical with a potential for
      human exposure. The likelihood for developmental toxicity was investigated in two
      species. Timed-pregnant CD rats and CD-1 mice were dosed daily by gavage with
      undiluted TEG over gestational days (gd) 5-15 at 0.0 (water control), 1126, 5630
      or 11,260 mg kg(-1) day(-1) with rats and 0.0, 563, 5630 or 11,260 mg kg(-1) day(
      1) with mice. They were examined daily, and gestational body weights and food and
      water consumption measured throughout gestation. At necropsy on gd 21 (rats) or
      gd 18 (mice) dams were examined for body, gravid uterine, liver and kidney
      weights, and implantation sites. Maternal kidneys were examined histologically.
      Fetuses were weighed, sex determined, and examined for external, soft tissue and
      skeletal variations and malformations. Rat dams had reduced body weights, body
      weight gains, and food consumption, and increased water consumption and relative
      kidney weights at 11,260 mg kg(-1) day(-1). They also had reduced body weight and
      increased water consumption at 5630 mg kg(-1) day(-1). Mice had clinical signs
      and increased relative kidney weight at 11,260 mg kg(-1) day(-1). Renal histology
      was normal in both species. Neither species had treatment-related effects on
      corpora lutea or implantations. Fetal body weights were reduced at 11,260 mg kg(
      1) day(-1) (both species) and 5630 mg kg(-1) day(-1) (mice). In rat fetuses there
      was a pattern of delayed ossification in the thoracic region at 11,260 mg kg(-1)
      day(-1). Mouse fetuses had delayed ossification in the frontal and supraoccipital
      bones, cervical region, hindlimb proximal phalanges and reduced caudal segments
      at 11,260 mg kg(-1) day(-1), and in the skull bones at 5630 mg kg(-1) day(-1).
      These patterns of delayed ossification are consistent with reduced fetal body
      weights. No biologically significant embryotoxicity or teratogenicity was
      observed at any dosage in either species. The NOEL for TEG given by gavage over
      the period of organogenesis was 1126 mg kg(-1) day(-1) in the rat and 5630 mg kg(
      1) day(-1) in the mouse for maternal toxicity, and 5630 mg kg(-1) day(-1) (rat)
      and 563 mg kg(-1) day(-1) (mouse) for developmental toxicology.

PMID- 16092105
TI  - Psychogenic tremor disorders identified using tree-based statistical algorithms
      and quantitative tremor analysis.
AB  - Detecting psychogenic tremors (PsychT) is often challenging. As there are no
      laboratory investigations or imaging techniques that can confirm the diagnosis,
      PsychT is identified on a clinical basis. We present a tree-based statistical
      algorithm derived from quantitative computerized tremor recordings as a novel
      method to help in the recognition of PsychT. The goal of this study was to show
      that objective data from computerized tremor recordings, when processed through a
      tree-based statistical algorithm, can be used to determine whether a patient can
      be classified as having PsychT.

PMID- 16092106
TI  - Relationship between eye symptoms and blepharospasm: a multicenter case-control
      study.
AB  - Although patients with primary blepharospasm (BSP) commonly report experiencing
      ocular symptoms before the onset of orbicular spasms, the precise frequency and
      pathogenic role of this subjective ocular discomfort are poorly understood. We
      conducted a multicenter case-control study to investigate symptoms related to
      disorders of the anterior segment of the eye, administering a questionnaire to
      165 patients with BSP and 180 age- and gender-matched control patients with
      hemifacial spasm. On a validation sample, our questionnaire yielded high accuracy
      in detecting eye diseases (predominantly, dry eye syndrome) using detailed
      ophthalmological examination as the criterion. Logistic regression analysis
      indicated a significant association between ocular symptoms at disease onset and
      BSP. Ocular symptoms starting in the year preceding disease onset (short-latency
      symptoms) showed a stronger association with BSP than ocular symptoms occurring
      earlier in time (long-latency symptoms). The association was stronger when short
      latency symptoms developed from 40 to 59 years of age, whereas this was not
      observed for long-latency symptoms. Our findings support the view that eye
      symptoms associated with BSP result from eye diseases and may be involved in the
      pathogenesis of BSP. The differential risk of developing BSP, based on age at
      onset of ocular symptoms, suggests that age and eye diseases may interact in
      giving rise to BSP.

PMID- 16092107
TI  - Case of symptomatic propriospinal myoclonus evolving toward acute "myoclonic
      status".
AB  - Propriospinal myoclonus is a rare motor disorder consisting of involuntary spinal
      generated muscular jerks. Here, we report a severe and uncommon case of
      propriospinal myoclonus that appeared after a vertebral fracture of T11. In this
      patient, the polysomnographic investigation showed continuing focal myoclonic
      activity in axial muscles during stable sleep and an acute progression into a
      myoclonic "status" associated with respiratory failure and loss of consciousness.
      It is necessary to consider this severe progression and support it with prompt
      emergency maneuvers and adequate pharmacotherapy.

PMID- 16092108
TI  - Frequent sequence variation at the ETM2 locus and its association with sporadic
      essential tremor in Korea.
AB  - Essential tremor (ET) is the most common but a complex neurological movement
      disorder. ET usually affects hands, but it may also affect head, neck, face, jaw,
      tongue, voice, trunk and, rarely, legs and feet. Although two susceptibility loci
      were identified on chromosome 2p24 (ETM2) and 3q13 (ETM1 or FET1), the exact
      transcript(s) has not been cloned. We analyzed unrelated Korean individuals with
      ET for a genetic association with three reported polymorphic loci (STS-etm1240,
      STS-etm1231, and STS-etm1234) in a candidate region on chromosome 2p24.1. We
      investigated sequence polymorphisms at these three loci in 30 ET patients and 30
      controls using polymerase chain reaction (PCR) amplification followed by sequence
      analysis. Eight different sequence variants (5 at etm1234, 2 at etm1240, and 1 at
      etm1231) were detected from 7 patients. Of interest, sequence variants were found
      only in classic ET patients but not in nonclassic ET patients and healthy
      individuals. Additionally, we also observed that a decrease in the number of
      short tandem repeats within etm1234 locus is more frequent in ET patients
      compared to controls. Our data thus support that ET development would be linked
      with the ETM2 locus and will facilitate the search for the ETM2 gene transcript.

PMID- 16092109
TI  - Dopaminergic influence on disturbed spatial discrimination in Parkinson's
      disease.
AB  - Various sensory symptoms and disturbed sensory perception are often observed in
      patients with idiopathic Parkinson's disease (PD). The basis of sensory
      disturbance in PD is unknown but possibly reflects a role for the basal ganglia
      in sensory processing. To investigate the relationship between the sensory
      dysfunction and dopaminergic deficiency in PD, we measured spatial discrimination
      using the Grating Orientation Task in 21 drug-naive patients with PD, before and
      after long-term antiparkinson therapy, and 25 age-matched healthy controls. The
      grating orientation threshold was significantly higher in patients (3.03 +/-
      0.84) than controls (2.03 +/- 0.79). After 3 to 10 months of antiparkinson
      therapy, the grating orientation threshold was significantly lowered (2.66 +/-
      0.84), although it was still higher than that in controls. Improvement in the
      patients' sensory function was significantly correlated with motor improvement (r
      = 0.44). These results suggest that sensory dysfunction in Parkinson's disease is
      related at least in part to the dopaminergic deficit.

PMID- 16092110
TI  - Very late-onset Friedreich's ataxia with minimal GAA1 expansion mimicking
      multiple system atrophy of cerebellar type.
AB  - Very late-onset Friedreich's ataxia (VLOFA) is characterized by symptomatic onset
      after 40 years of age and, usually, a benign phenotype. We describe a sporadic
      case with onset at 53 years of age and a novel VLOFA phenotype mimicking multiple
      system atrophy (MSA) of cerebellar type associated with minimal GAA1 expansion.
      We detected several atypical features for a diagnosis of MSA, which should alert
      to the possibility of an inherited ataxia.

PMID- 16092111
TI  - Rat bone marrow stromal cell osteogenic differentiation and fibronectin
      adsorption on chitosan membranes: the effect of the degree of acetylation.
AB  - Cell adhesion, migration, and proliferation of a few anchorage-dependent cells
      cultured on chitosan (Ch) matrices are influenced by the degree of N-acetylation
      (DA) of Ch. In the present work, we examined the influence of the DA on the
      attachment, spreading, proliferation, and osteogenic differentiation of rat bone
      marrow stromal cells (rBMSCs). Ch membranes were characterized in terms of
      surface morphology, roughness, and wettability, and in terms of adsorption of an
      adhesive protein, fibronectin (Fn). Chs with DAs in the range of 4 to 49% were
      used. Among the Ch samples, the DA of 4% led to the highest Fn surface
      concentration, both from single protein solution and from diluted serum.
      Furthermore, the levels of Fn adsorbed from serum found for this DA were
      threefold higher than for the tissue culture polystyrene control, indicating that
      in the presence of competitive proteins Ch is more specific toward Fn adsorption
      than tissue culture polystyrene. rBMSCs cultured on Ch carrying a DA of 4% were
      able to spread, proliferate, and differentiate, reaching a higher level of
      osteogenic differentiation than on the control, despite the lower cell attachment
      observed for all Ch samples. Because the Ch sample with a DA of 4% showed the
      highest Fn adsorption from serum, we suggest that cell adhesion, spreading, and
      osteogenic differentiation of rBMSCs on Ch may be mediated by the adsorbed layer
      of Fn.

PMID- 16092112
TI  - In vitro evaluation of biocompatibility of beta-tricalcium phosphate-reinforced
      high-density polyethylene; an orthopedic composite.
AB  - Beta-tricalcium phosphate-reinforced high-density polyethylene (beta-TCP/HDPE) is
      a new biomaterial which was made as a copy of bone composition with the aim of
      replacement of bony tissues. The composite samples were prepared using medical
      grade TCP powder and granular polyethylene. The raw materials were first
      compounded and the resulting composite preforms were compression molded into
      desired shape. The biocompatibility of composite samples with different volume
      fractions of TCP (20, 30, and 40 vol %) was assessed by proliferation, alkaline
      phosphatase (ALP), and cell adhesion assays using G-292 osteoblast cells. Cell
      material interaction on the surface of the composites was observed by scanning
      electron microscopy (SEM). The effect of beta-TCP/HDPE on the behavior of G-292
      cells was compared with those of a composite and a negative control samples.
      Results showed the composite samples had a higher proliferation rate of G-292
      cells in the presence of composite samples as compared to the composite control
      sample after 3, 7, and 14 days of incubation period. ALP production after
      incubation in the presence of composite samples was seen to peak on the day 7.
      The number of adhered cells on the composite samples was higher than the numbers
      adhered on composite and negative control samples after the above incubation
      periods. Morphology investigation of adhered cells by SEM indicated a normal
      morphology and also many of the cells were in the process of cell division. The
      above results indicate that beta-TCP/HDPE samples are biocompatible, nontoxic,
      and in some cases show an increase in the proliferation rate of the cells, ALP
      production, and cell adhesion as compared to the control counterparts.

PMID- 16092113
TI  - Chitosan-alginate as scaffolding material for cartilage tissue engineering.
AB  - Tissue compatibility of chitosan-alginate scaffolds was studied in vitro in terms
      of cell morphology, proliferation, and functionality using HTB-94 cells. The
      scaffold has an interconnected 3D porous structure, and was fabricated by
      thermally induced phase separation followed by freeze drying. Cell proliferation
      on the chitosan-alginate scaffold was found to be faster than on a pure chitosan
      scaffold. After cell culture for 2 weeks in vitro, the cells on the chitosan
      scaffold gradually assumed a fibroblast-like morphology while the cells on the
      chitosan-alginate scaffold retained their spherical morphology throughout the
      period of study. SDS-PAGE electrophoresis and Western blot assays for proteins
      extracted from cells grown on scaffolds indicated that production of cartilage
      specific collagen type II, a marker for chondrocytic phenotype, increased from
      week 2 to week 3 on the chitosan-alginate scaffold but decreased on the chitosan
      scaffold. This study suggested that chitosan-alginate scaffolds promote cell
      proliferation, enhance phenotype expression of HTB-94 chondrocytes, and may
      potentially serve as an improved alternative to chitosan scaffolds for cartilage
      tissue engineering.

PMID- 16092114
TI  - The effect of hyaluronic acid with different molecular weights on collagen
      crosslink synthesis in cultured chondrocytes embedded in collagen gels.
AB  - Hyaluronic acid (HA) is a component of the extracellular matrix of cartilage and
      has various effects on three-dimensional cultured chondrocytes. We measured
      Pyridinoline (Pyr), which is a crosslink of collagen in cultured chondrocyte
      collagen composites treated with HA of different molecular weights to investigate
      the effects of the various molecular weights on collagen crosslink synthesis. The
      control group was collagen gel without cells; group N was treated without HA; and
      the others were treated with HA with an average molecular weight of 2.3 x10(6) Da
      (group H), 8.0 x10(5) Da (group M), and 2.3 x10(4) Da (group L). In the control
      group, the Pyr content decreased, at week 4, being one-tenth that of preculture
      levels. In groups H and M, it was significantly greater than that in groups L and
      N at week 4. Pyr/hydroxyproline, which indicates the concentration of Pyr per
      collagen, decreased greatly in the control group at week 3. In groups H and M, it
      was significantly higher than that in groups L and N at week 4 and increased to
      80 and 76% of normal rabbit articular cartilage, respectively. The concentration
      of Pyr per collagen in cultured chondrocyte-collagen composites was similar to
      that of normal articular cartilage in vivo, and higher molecular weight HA may
      have a greater effect on the maturation of collagen in the composite.

PMID- 16092115
TI  - Genetic expression profiles and biologic pathway alterations in head and neck
      squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is associated with considerable
      mortality and morbidity and is a major public health concern worldwide. To date,
      > 20 studies incorporating DNA microarray analyses have examined genomewide
      genetic expression changes associated with the development of HNSCC. The authors
      identified published reports of genetic expression profiles of HNSCC by Medline
      database search. They performed a review of the reports to identify genes that
      have been found repeatedly to exhibit substantially altered expression in HNSCC.
      Genes with altered expression were subsequently examined in the context of
      defined biologic systems with the use of GenMapp 2.0 pathway analysis software.
      Genes most commonly found to exhibit altered expression were those encoding for
      cytoskeletal and extracellular matrix proteins, inflammatory mediators, proteins
      involved in epidermal differentiation, and cell adhesion molecules. Results of
      GenMapp 2.0 analysis suggested global down-regulation of genes that encode for
      ribosomal proteins and enzymes in the cholesterol biosynthesis pathway; and up
      regulation of genes that encode for matrix metalloproteinases and genes that bear
      on the inflammatory response. The review indicated that there are several genes
      and pathways that exhibit substantially altered expression in cancerous versus
      noncancerous states across studies. Further investigation into the genomic,
      proteomic, and functional consequences of these gene expression alterations may
      provide insight into the pathophysiology of HNSCC.

PMID- 16092116
TI  - Medicine-taking behavior: implications of suboptimal compliance in Parkinson's
      disease.
AB  - Management of Parkinson's disease (PD) depends primarily on oral medication.
      There are several drug classes and multiple doses and formulations, which make
      optimizing therapy complex. Variable drug absorption and the short half-life of
      most antiparkinson treatments, especially levodopa, are a main focus in
      understanding complications and have encouraged alternative delivery systems to
      limit fluctuation and dyskinesia at later stages. Comparatively little attention
      is paid to the way patients take their oral medication. Variable medicine-taking
      behavior can affect the clinician's understanding of the diagnosis and rate of
      progression, and further prescription of PD medication. Medicine overuse in later
      stage PD is well documented and causes psychiatric disturbance and increases
      motor complications, but evidence of undertreatment and erratic intake is
      emerging, which is likely to affect motor control and quality of life adversely.
      Methods of quantifying compliance are compared for accuracy and limitations.
      Understanding medicine-taking behavior is a first step in optimizing therapy and
      requires consideration of a patient's personal beliefs about their medicines.
      Although the benefits of regularizing oral medicine-taking in a practical,
      achievable way in PD remain untested, such an approach might prolong and smooth
      the benefits of oral medication and is worthy of further research.

PMID- 16092117
TI  - Diagnostic significance of reduced serum caeruloplasmin concentration in
      neurological disease.
AB  - This study covers patients seen at a Wilson disease clinic between 1960 and 2002.
      The diagnosis of Wilson disease was confirmed in 316. Of 40 patients with a
      neurological presentation who were found not to have the disease, caeruloplasmin
      concentration was found to be reduced in 19. These 19 patients comprised 17 men
      and 2 women. The various diagnoses included Huntington's disease, multiple
      sclerosis, subacute sclerosing panencephalitis (SSPE), Hallervorden Spatz
      syndrome, and acaeruloplasminemia; in 9 no definite diagnosis was made. In view
      of the marked male preponderance, the lower limit of caeruloplasmin is calculated
      as for males. In an earlier study this was found to be 33.3 mg/dl (standard
      deviation, 6.1 mg/dl); therefore, 21.1 mg/dl is taken as the lower limit of
      normal. Particular attention is paid to 3 patients, 2 of whom had zero
      concentrations of caeruloplasmin and 1 had a very low level of the protein. Only
      1 of these patients conformed to the classical picture of acaeruloplasminemia.
      The significance of a low caeruloplasmin concentration in patients with a variety
      of neurological syndromes is not clear but can lead to diagnostic confusion. When
      the concentration of this protein is very low or absent the diagnosis of
      acaeruloplasminemia must be considered.

PMID- 16092118
TI  - Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation,
      apoptosis, signaling, and angiogenesis.
AB  - BACKGROUND: Because a role for nuclear factor-kappaB (NF-kappaB) has been
      implicated in the pathogenesis of pancreatic carcinoma, this transcription factor
      is a potential target for the treatment of this devastating disease. Curcumin
      (diferuloylmethane) is a phytochemical with potent NF-kappaB-inhibitory activity.
      It is pharmacologically safe, but its bioavailability is poor after oral
      administration. METHODS: The authors encapsulated curcumin in a liposomal
      delivery system that would allow intravenous administration. They studied the in
      vitro and in vivo effects of this compound on proliferation, apoptosis,
      signaling, and angiogenesis using human pancreatic carcinoma cells. NF-kappaB was
      constitutively active in all human pancreatic carcinoma cell lines evaluated and
      liposomal curcumin consistently suppressed NF-kappaB binding (electrophoretic
      mobility gel shift assay) and decreased the expression of NF-kappaB-regulated
      gene products, including cyclooxygenase-2 (immunoblots) and interleukin-8 (enzyme
      linked immunoassay), both of which have been implicated in tumor
      growth/invasiveness. These in vitro changes were associated with concentration
      and time-dependent antiproliferative activity (3-[4,5-dimethylthiazol-2-yl]2,5
      diphenyltetrazolium bromide assay [MTT assay]) and proapoptotic effects (annexin
      V/propidium iodide staining [fluorescence-activated cell sorting] and
      polyadenosine-5'-diphosphate-ribose-polymerase cleavage). RESULTS: The activity
      of liposomal curcumin was equal to or better than that of free curcumin at
      equimolar concentrations. In vivo, curcumin suppressed pancreatic carcinoma
      growth in murine xenograft models and inhibited tumor angiogenesis. CONCLUSIONS:
      Liposomal curcumin down-regulated the NF-kappaB machinery, suppressed growth, and
      induced apoptosis of human pancreatic cells in vitro. Antitumor and
      antiangiogenesis effects were observed in vivo. The experiments in the current
      study provide a biologic rationale for treatment of patients suffering from
      pancreatic carcinoma with this nontoxic phytochemical encapsulated in liposomes
      for systemic delivery.

PMID- 16092119
TI  - Colorectal carcinoma screening procedure use among primary care patients.
AB  - BACKGROUND: Despite evidence-based recommendations for colorectal carcinoma
      screening, population-based surveys report low screening rates. To the authors'
      knowledge, the extent to which screening procedures are used by patients seen in
      primary care is not as clear. The authors estimated the annual and 5-year
      colorectal carcinoma screening procedure use among a cohort of primary care
      patients and evaluated the correlation between patient characteristics and the
      use of screening procedures. METHODS: The authors identified a cohort of patients
      (n = 21,833 patients) ages 55-70 years who had a primary care visit in 2003 and
      who were enrolled in a health plan for the 5-year period ending December 31,
      2003. Using automated data for the 5-year period ending December 31, 2003,
      information on patient sociodemographic characteristics, primary care and health
      maintenance examination (HME) visits, comorbid diagnoses, income, and screening
      receipt was compiled. The latter included barium enema, colonoscopy, fecal occult
      blood testing (FOBT), and flexible sigmoidoscopy use. RESULTS: Approximately one
      half of insured, primary care patients (54%) received recommended colorectal
      carcinoma screening procedures over the 5-year observation period. Among
      individuals who received screening, colonoscopy was used most frequently (39.9%),
      followed by flexible sigmoidoscopy testing alone (28.3%) or in combination with
      FOBT (4.3%). Annual screening rates increased by 3.1% between 1999 and 2003.
      Among individuals who did not receive recommended colorectal carcinoma screening,
      64% had at least 3 HME visits, and 41% received at least 1 FOBT. Increasing HME
      visits and other primary care visit frequency, along with increasing age, income,
      male gender, and African-American race, were associated with screening receipt.
      CONCLUSIONS: Significant opportunities exist to increase colorectal carcinoma
      screening among primary care patients.

PMID- 16092120
TI  - Trisomy 20q13 --> 20qter in a girl with multiple congenital malformations and a
      recombinant chromosome 20 inherited from a paternal inversion (20)(p13q13.1):
      clinical report and review of the trisomy 20q phenotype.
AB  - We report on a patient with a rec(20)dup(20q) chromosome abnormality derived from
      a paternal chromosome 20 inversion [inv(20)(p13q13.1)]. The rearrangement results
      in a duplication of 20q13.1 to 20qter and a deletion of 20p13 to 20pter. The
      patient is a girl with craniofacial features and multiple congenital
      malformations that overlap with the abnormalities previously described in trisomy
      20q syndrome. To our knowledge this is the first report of a patient with
      rec(20)dup 20q.

PMID- 16092121
TI  - Pigmentary mosaicism following the lines of Blaschko in a girl with a double
      aneuploidy mosaicism: (47,XX,+7/45,X).
AB  - We report on a 6-year-old girl with linear streaks of apparent hypopigmentation
      and hyperpigmentation following the Blaschko lines, growth retardation,
      bupthalmos of the left eye, and mild mental retardation. She had a 45,X karyotype
      in lymphocytes. In cultured fibroblasts a double aneuploidy mosaicism was
      detected, consisting of a cell line with trisomy for chromosome 7 and a cell line
      with monosomy for the X-chromosome and no cell line with a normal karyotype.
      Cutis tricolor or three levels of pigmentation in different skin areas suggested
      presence of a third, probably normal cell line. Double aneuploidy mosaicism of a
      cell line with monosomy X and a cell line with trisomy of an autosome is a rare
      finding. The combination of monosomy X with trisomy of chromosomes 8, 10, 13, 18,
      and 21 has been reported, but not the combination with trisomy 7. In the 45,X
      cell line, microsatellite analysis showed loss of the maternal X-chromosome, and
      presence of a maternal and paternal chromosome 7. The 47,XX,+7 cell line showed a
      paternal and a maternal X-chromosome, and a paternal and two identical maternal
      chromosomes 7. Mechanisms that might explain this double aneuploidy mosaicism are
      discussed.

PMID- 16092122
TI  - Brachydactylic multiple delta phalanges plus syndrome.
AB  - Delta phalanges are unusual, shortened bones of the hands and feet with abnormal
      epiphyses and diaphyses. Here, we report on a patient with a unique multiple
      congenital anomaly syndrome that includes brachydactyly consisting of multiple
      delta phalanges in several digits of the hands and feet. The patient, who was
      born to consanguineous parents, had several other congenital anomalies, including
      butterfly vertebrae, craniofacial dysmorphism, and coarctation of the aorta. We
      have called this distinctive condition "brachydactylic multiple delta phalanges
      plus syndrome." Although no other member of the family had obvious hand or foot
      anomalies, several siblings had other malformations. Possible modes of
      inheritance in this family include variable expression of a recessive or de novo
      dominant condition.

PMID- 16092123
TI  - Coincidence of a right retroaortic circumflex coronary artery and a right-sided
      aortic arch with a retroesophageal course of the left subclavian artery (arteria
      lusoria).
AB  - An anomalous branch of the right coronary artery was found in a 71-year-old male
      cadaver with a right-sided aortic arch. The anomalous artery arose from the
      proximal portion of the right coronary artery and ran in a retroaortic course,
      before reaching the posterior wall of the heart. It was recognized as the right
      sided variation of the circumflex coronary artery. The aortic arch had as
      branches the left common carotid, right common carotid, right subclavian, and
      left subclavian arteries, in that order, and the descending aorta was located in
      the right thorax. The left subclavian artery arose from a Kommerell's
      diverticulum and ran behind the esophagus, and the left-sided ligamentum
      arteriosum was also connected at the diverticulum. Therefore, the right aortic
      arch was classified as type N according to Adachi-Williams-Nakagawa and type III
      B1 in accordance with Stewart-Edwards. The Kommerell's diverticulum in this case
      seemed to press on the posterior wall of the esophagus.

PMID- 16092124
TI  - Accessory joints between basiocciput and atlas/axis in the median plane.
AB  - To explore the many osseous irregularities that are found in the area between the
      basiocciput, the anterior arch of the atlas and the tip of the dens axis we
      studied 99 cadaver specimens using magnetic resonance tomography (MRT), computed
      tomography (CT), median saw-cut sections, and histological sections.
      Additionally, "dry" specimens of the skull (n = 110), atlas (n = 56), and axis (n
      = 33) were investigated. In the median plane, the dry and cadaver specimens
      exhibited osteoarthritis-related osseous outgrowths and osteophytes of the
      articular surfaces of the median atlanto-axial joint (n = 63), and the presence
      of congenitally developed free ossicles (n = 22) and of third occipital condyles
      (n = 3). The largest osteophytes (giant osteophytes) (n = 4) of the anterior arch
      of the atlas formed osseous contact zones with the basiocciput that were visible
      histologically as real joints and were designated accessory median atlanto
      occipital joints. The third occipital condyles also formed osseous contact zones,
      visible histologically as real joints, with the anterior arch of the atlas or
      with the tip of the dens, and were designated accessory atlanto-occipital or
      occipito-odontoid joints. Frequent free ossicles, incorporated into the accessory
      joint, were found by histological examination to be covered with hyaline
      cartilage.

PMID- 16092125
TI  - Role of the C2 articular branches in occipital headache: an anatomical study.
AB  - One of the most important structures involved in the pathogenesis of occipital
      headache is the lateral atlanto-axial joint. Previous studies demonstrated that
      injection of this joint with local anesthetic can alleviate occipital headache,
      while injection of contrast medium exacerbates it. The aim of our study is to
      improve the understanding of the nerve supply to the lateral atlanto-axial joint
      by the C2 nerve elements, in order to determine the optimal target for an
      anesthetic block of this area. Ten C2 spinal nerves and roots were dissected in
      five embalmed cadavers with the aid of a 40X microscope and the lateral atlanto
      axial joint was shown to be extensively supplied by articular branches of C2
      nerve elements (dorsal ganglion, spinal nerve, and ventral ramus). Following our
      observations on their distribution, we propose a target for local anesthetic
      injection of the C2 articular branches that is based on reliable landmarks and is
      easily identifiable at fluoroscopy. We suggest that local anesthetic injection at
      this target point could be of benefit in the relief of occipital pain due to
      cervical trauma or degenerative disease involving the lateral atlanto-axial
      joint.

PMID- 16092126
TI  - Fetal azygos pericallosal artery.
AB  - An unpaired trunk forming part of the anterior cerebral arteries, the so-called
      azygos pericallosal artery, was found in a male fetus among a collection of 200
      fetuses. The morphological characteristics of the trunk and the anterior cerebral
      arteries at the "preazygos" and the "postazygos" segments were examined using an
      operating microscope. The azygos pericallosal artery distributes into three
      postazygos segments of which only the median postazygos segment or median
      callosal artery had a bihemispheric distribution of its branches to the medial
      telencephalic surfaces.

PMID- 16092127
TI  - Artificial deformation of the human skull: a review.
AB  - Early examples of intentional human cranial deformation predate written history.
      Intentional cranial deformation as an extreme has seemingly not persisted into
      this century. However, mild forms of this manipulation are still practiced by
      various groups worldwide. Accidental cranial deformation or mild forms of
      intentional cranial deformation may be encountered by the clinician or anatomist.
      We review the literature regarding intentional manipulation of the human cranium.

PMID- 16092128
TI  - Steroid hormone receptor signaling in tumorigenesis.
AB  - Excessive activation of the hormone signaling pathways is implicated in several
      disorders of the target tissues, with cancer being one of the most serious
      fallouts. Steroid hormone receptors are key proteins through which steroid
      hormones convey their signals to the cells. Deregulated activity of the hormone
      receptors due to their altered activation; stability or sub-cellular localization
      is heavily implicated in the onset and progress of cancers. The role played by
      estrogen and its receptors in breast cancer remains the most thoroughly
      investigated steroid-dependent cancer system till date. Choosing it as an
      example, we have summarized the molecular mechanisms underlying the action of the
      estrogen receptors (ERs) in manifesting the effects of the estrogens in the
      cells. A special emphasis is placed on the molecular mechanism of their
      functionality, role of the coactivator proteins, and the reasons for the
      deregulated signaling. The therapeutic approaches resulting from the mechanistic
      study of the ER action and their efficacies are also discussed.

PMID- 16092129
TI  - Structure and size of bronchopulmonary anastomoses in sheep lung.
AB  - The distribution and drainage of bronchial arterial blood flow are complex. We
      used two different methods to study the bronchial-pulmonary anastomoses in sheep
      lung. Initially, we injected two different sizes of fluorescent microspheres (15
      and 100 microm diameter) into the bronchial artery and histologically determined
      where the different-size microspheres were entrapped in the lung. In a second
      series of animals, we injected Microfil into the bronchial artery to observe the
      anastomotic vessels. The microsphere data confirmed the existence of bronchial-to
      pulmonary anastomoses. No microspheres were found in the systemic organs (heart
      and kidney), confirming the absence of large bronchial artery-to-pulmonary vein
      anastomoses. Unexpectedly, proportionately more large microspheres (100 microm)
      lodged in the alveolar parenchyma when compared to 15 microm microspheres. This
      suggests that there are many more small bronchial (< 100 microm) arterioles
      feeding the airway mucosa than the larger anastomotic vessels feeding into the
      parenchyma. In the Microfil cast lungs, we observed four types of anastomotic
      vessels: bronchial arteries/arterioles that anastomose with pulmonary
      arteries/arterioles that accompany airways; bronchial arterioles that anastomose
      directly with parenchymal (and eventually alveolar) vessels; bronchial arterioles
      that anastomose with blood vessels that do not accompany airways; and bronchial
      arterioles that anastomose with bronchial veins. Based on our in vivo microsphere
      data, the vessels that do not accompany the airways are most likely bronchial
      venules, not pulmonary venules.

PMID- 16092130
TI  - Levator palpebrae superioris muscle in human fetuses: anatomical findings and
      their clinical relevance.
AB  - Accessory medial muscular bellies of the levator palpebrae superioris muscle and
      broad lateral insertion of its aponeurosis into tissue near the lacrimal gland
      have been reported as rare variations in adults. The anatomy of this muscle was
      studied in orbits of ten human fetuses between the 5th and 10th months of
      gestation. In each of the dissected orbits, the levator palpebrae superioris
      muscle had a broad lateral insertion into the capsule of the lacrimal gland or
      the periorbita, in this period of development. In addition, medial accessory
      muscles of the levator or singular muscle fibers within fibrous bands that
      inserted near the trochlear region and the medial portion of the upper eyelid
      were present in 70% of the fetuses, either unilaterally or bilaterally. These
      findings demonstrate new unreported aspects of levator palpebrae superioris
      development and morphology. Our findings suggest that an initial broad anterior
      primary anlage of the muscle is followed by secondary atrophy of lesser used
      marginal portions of this muscle, which are replaced by delicate connective
      tissue. These findings might force new considerations about diagnostic and
      therapeutic approaches to congenital mobility disorders of the levator palpebrae
      superioris muscle, such as blepharoptosis or eyelid retraction. The clinical
      relevance of our results are discussed along with a review of the embryogenesis
      of extraocular muscles and soft tissue of the orbit.

PMID- 16092131
TI  - A Bayesian approach to determining connectivity of the human brain.
AB  - Recent work regarding the analysis of brain imaging data has focused on examining
      functional and effective connectivity of the brain. We develop a novel
      descriptive and inferential method to analyze the connectivity of the human brain
      using functional MRI (fMRI). We assess the relationship between pairs of distinct
      brain regions by comparing expected joint and marginal probabilities of elevated
      activity of voxel pairs through a Bayesian paradigm, which allows for the
      incorporation of previously known anatomical and functional information. We
      define the relationship between two distinct brain regions by measures of
      functional connectivity and ascendancy. After assessing the relationship between
      all pairs of brain voxels, we are able to construct hierarchical functional
      networks from any given brain region and assess significant functional
      connectivity and ascendancy in these networks. We illustrate the use of our
      connectivity analysis using data from an fMRI study of social cooperation among
      women who played an iterated "Prisoner's Dilemma" game. Our analysis reveals a
      functional network that includes the amygdala, anterior insula cortex, and
      anterior cingulate cortex, and another network that includes the ventral
      striatum, orbitofrontal cortex, and anterior insula. Our method can be used to
      develop causal brain networks for use with structural equation modeling and
      dynamic causal models.

PMID- 16092132
TI  - Hemispheric asymmetry of sulcus-function correspondence: quantization and
      developmental implications.
AB  - Spatial covariances between the geometric centers of human occipital sulci and
      visual functional areas were calculated to reduce the spatial variance of
      functional-area locations between subjects. Seven visual areas in each occipital
      hemisphere were retinotopically mapped, using horizontal- and vertical-meridian
      stimuli and (15)O PET in 11 subjects. Sulcal locations were determined using
      anatomic brain models derived from high-resolution MRI images. Location
      variability for sulci and functional areas was similar in magnitude, with average
      standard deviations of (2.7x, 5.3y, 5.7z) mm and (4.3x, 5.4y, 5.3z) mm,
      respectively. Sulcal locations were predictive of functional-area locations
      (i.e., significant spatial covariance) in the minority of structure-function
      pairings tested (25 of 168). Location variability was reduced by an average of
      27% for functional areas showing significant covariation with sulcal features.
      Early-developing sulci were stronger predictors of functional-area location than
      late-developing sulci. Sulcus-function covariance was stronger in the left
      occipital lobe than in the right occipital lobe. Notably, the left calcarine
      fissure demonstrated powerful covariances with functional areas in both
      hemispheres, suggesting that it serves as a developmental "anchor" for functional
      areas in the occipital cortex. These findings support the hypothesis that
      hemispheric lateralization of function is reflected in the strength of
      correspondence between cortical surface anatomy and function.

PMID- 16092133
TI  - Ventral-striatal/nucleus-accumbens sensitivity to prediction errors during
      classification learning.
AB  - A prominent theory in neuroscience suggests reward learning is driven by the
      discrepancy between a subject's expectation of an outcome and the actual outcome
      itself. Furthermore, it is postulated that midbrain dopamine neurons relay this
      mismatch to target regions including the ventral striatum. Using functional MRI
      (fMRI), we tested striatal responses to prediction errors for probabilistic
      classification learning with purely cognitive feedback. We used a version of the
      Rescorla-Wagner model to generate prediction errors for each subject and then
      entered these in a parametric analysis of fMRI activity. Activation in ventral
      striatum/nucleus-accumbens (Nacc) increased parametrically with prediction error
      for negative feedback. This result extends recent neuroimaging findings in reward
      learning by showing that learning with cognitive feedback also depends on the
      same circuitry and dopaminergic signaling mechanisms.

PMID- 16092134
TI  - Significance of the latissimus dorsi for shoulder instability. I. Variations in
      its anatomy around the humerus and scapula.
AB  - In a cadaveric instability model that leaves all muscles intact initially, we
      studied anteroinferior glenohumeral dislocation behavior after section of the
      ligaments on the humeral side of the joint. In this study, the latissimus dorsi
      seemed to play a role when complete section did not result in a locked
      anteroinferior dislocation. We therefore initiated a study to test the hypothesis
      that the latissimus dorsi may, in certain circumstances, depending on variations
      in its anatomy, influence dislocation behavior. Here, in Part I, we present the
      results of the anatomic study of latissimus dorsi and its tendons. The anatomy of
      the latissimus dorsi pertaining to the scapula and humerus was studied in 100
      cadaver specimens. The distance between the uppermost part of the tendon of both
      the latissimus dorsi and the teres major and the edge of the articular cartilage
      of the humeral head (tendon-cartilage distance, TCD) as well as the width and
      length of the tendons were measured. Furthermore, the relationship between
      latissimus dorsi and the inferior angle of the scapula was studied. The tendon of
      the latissimus dorsi inserted at a variable distance from the cartilage of the
      humeral head: the TCD ranged from 12.6 to 31.6 mm (mean 21.06 mm+/-5.11 mm). The
      latissimus dorsi can have muscular fibers arising from the inferior angle of the
      scapula (type 1 scapular connection, 43%). Alternatively, there may be only a few
      fibrous strands between the muscle and the scapula or there may be an intervening
      bursa (type 2 scapular connection, 57%). This variability in the morphology of
      the latissimus dorsi may be a factor explaining the differences observed in a
      study of humerus-based sequential cutting of the glenohumeral capsule. This
      possibility is explored in Part II of the study. The latissimus dorsi may also
      complete the tendinous protection of the humeral side of the capsule generally
      provided by the rotator cuff.

PMID- 16092135
TI  - Trabecular rod buckling index in thoraco-lumbar vertebral bonedagger.
AB  - The need for improved mechanistic understanding of cancellous bone failure is at
      the core of important clinical problems such as osteoporosis, as well as basic
      biological issues such as bone formation and adaptation. Three-dimensional (3D)
      anaglyphs were produced from 15 T12 and L1 vertebral bodies, which encompass the
      adult life span in both sexes. The anaglyphs were viewed with red-green stereo
      glasses, using an image analyzer, and trabecular thickness and trabecular length
      were measured. From biomechanical principles, the strength of individual
      trabeculae can be estimated from measurement of trabecular rod thickness and
      trabecular rod length as the load to buckling index. The distribution of the load
      to buckling index was best described by a log normal curve. Trabecular rod
      thickness, trabecular rod length, and load to buckling index for males were
      consistently greater than for females. With aging, trabecular rod thickness, and
      the load to buckling index decrease for males while trabecular rod length
      increases for females. In this study, the load to buckling index for thoraco
      lumbar vertebral trabecular rods potentially quantifies a greater risk of
      vertebral fracture for females. Decreased trabecular rod thickness or increased
      trabecular rod length result in the strength of trabeculae shifting closer to a
      putative fracture threshold. The corollary being that there is a reduced safety
      margin for resistance to mechanical loads for the vertebral bodies. The 3D
      anaglyph technique for measuring trabecular dimensions provides an accurate and
      precise methodology by which these morphological studies can be undertaken.

PMID- 16092137
TI  - Reversible, strain-controlled haptotropic shifts of cyclopentadienyl ligands in
      [1]- and [2]metallocenophanes.

PMID- 16092138
TI  - New iodination reactions of saturated hydrocarbons.

PMID- 16092139
TI  - 9/11 mixed helices in alpha/beta peptides derived from C-linked carbo-beta-amino
      acid and L-Ala repeats.

PMID- 16092140
TI  - Structure and IR spectrum of phenylalanyl-glycyl-glycine tripetide in the gas
      phase: IR/UV experiments, ab initio quantum chemical calculations, and molecular
      dynamic simulations.
AB  - We investigated the potential-energy surface (PES) of the phenylalanyl-glycyl
      glycine tripeptide in the gas phase by means of IR/UV double-resonance
      spectroscopy, and quantum chemical and statistical thermodynamic calculations.
      Experimentally, we observed four conformational structures and we recorded their
      IR spectra in the spectral region of 3000-4000 cm(-1). Computationally, we
      investigated the PES by a combination of molecular dynamics/quenching procedures
      with high-level correlated ab initio calculations. We found that neither
      empirical potentials nor various DFT functionals provide satisfactory results. On
      the other hand, the approximative DFT method covering the dispersion energy
      yields a reliable set of the most stable structures, which we subsequently
      investigated with an accurate, correlated ab initio treatment. The global minimum
      contains three moderately strong intramolecular hydrogen bonds and is mainly
      stabilized by London dispersion forces between the phenyl ring, the carboxylic
      acid group, and various peptide bonds. A proper description of the last type of
      interaction requires accurate correlated ab initio calculations, including the
      complete basis set limit of the MP2 method and CCSD(T) correction terms. Since in
      our beam experiments the conformations are frozen by cooling from a higher
      temperature, it is necessary to localize the most stable structures on the free
      energy surface rather than on the PES. We used two different procedures (rigid
      rotor/harmonic oscillator/ideal gas approximation based on ab initio
      characteristics and evaluation of relative populations from the molecular dynamic
      simulations using the AMBER potential) and both yield four structures, the global
      minimum and three local minima. These four structures were among the 15 most
      energetically stable structures obtained from accurate ab initio optimization.
      The calculated IR spectra for these four structures agree well with the
      experimental frequencies, which validates the localization procedure.

PMID- 16092141
TI  - Unique nanoscale morphologies underpinning organic gel-phase materials.
AB  - This study investigates the self-assembly of simple aliphatic diamines with a
      dendritic peptide. By controlling the molar ratio of this two-component system,
      new nanoscale morphologies were generated. In the presence of relatively long
      aliphatic chains (C10, C12) a transition from nanoscale fibres to platelets was
      observed on changing the molar ratio, whereas, for shorter spacer chains (e.g.,
      C9 and C8), interesting and unique morphological changes were observed by low
      voltage field emission gun scanning electron microscopy (SEM), with "nanosquares"
      or nanoscale "rosette" structures being formed. Remarkably, these discrete
      nanoscale structures were able to form sample-spanning networks capable of
      supporting a gel-phase material; whereas, most gels are usually based on
      fibrillar assemblies. In addition to SEM, the gels were characterised by using
      thermal measurements and circular dichroism spectroscopy. The length of the
      diamine spacer and the molar ratio of components controlled the self-assembly
      process by modifying the spatial organisation of the dendritic head groups at the
      molecular level, which is transcribed into the aspect ratio of the self-assembled
      state at the microscopic level. Ultimately, this led to diamine-induced control
      of the macroscopic material's behaviour. When present in excess, the diamine
      controlled the observed nanoscale morphology as a consequence of undergoing a
      dendritically controlled nanocrystallisation process to form a network, an
      unusual and significant result.

PMID- 16092143
TI  - Controlled hydrothermal synthesis of bismuth oxyhalide nanobelts and nanotubes.
AB  - Ternary bismuth oxyhalide crystalline nanobelts (such as Bi24O31Br10, Bi3O4Br,
      Bi12O17Br2, BiOCl, and Bi24O31Cl10) and nanotubes (such as Bi24O31Br10) have been
      synthesized by using convenient hydrothermal methods. The composition and
      morphologies of the bismuth oxyhalides could be controlled by adjusting some
      growth parameters, including reaction pH, time, and temperature. All the
      nanostructures were characterized by using various methods including X-ray
      diffraction, transmission electron microscopy, high-resolution TEM, electron
      diffraction, and energy-dispersive X-ray analysis. The possible reaction
      mechanism and growth of the crystals are discussed based on the experimental
      results.

PMID- 16092142
TI  - Synthetic scope and mechanistic studies of Ru(OH)x/Al2O3-catalyzed heterogeneous
      hydrogen-transfer reactions.
AB  - Three kinds of hydrogen-transfer reactions, namely racemization of chiral
      secondary alcohols, reduction of carbonyl compounds to alcohols using 2-propanol
      as a hydrogen donor, and isomerization of allylic alcohols to saturated ketones,
      are efficiently promoted by the easily prepared and inexpensive supported
      ruthenium catalyst Ru(OH)x/Al2O3. A wide variety of substrates, such as aromatic,
      aliphatic, and heterocyclic alcohols or carbonyl compounds, can be converted into
      the desired products, under anaerobic conditions, in moderate to excellent yields
      and without the need for additives such as bases. A larger scale, solvent-free
      reaction is also demonstrated: the isomerization of 1-octen-3-ol with a
      substrate/catalyst ratio of 20,000/1 shows a very high turnover frequency (TOF)
      of 18,400 h(-1), with a turnover number (TON) that reaches 17,200. The catalysis
      for these reactions is intrinsically heterogeneous in nature, and the
      Ru(OH)x/Al2O3 recovered after the reactions can be reused without appreciable
      loss of catalytic performance. The reaction mechanism of the present
      Ru(OH)x/Al2O3-catalyzed hydrogen-transfer reactions were examined with
      monodeuterated substrates. After the racemization of (S)-1-deuterio-1
      phenylethanol in the presence of acetophenone was complete, the deuterium content
      at the alpha-position of the corresponding racemic alcohol was 91%, whereas no
      deuterium was incorporated into the alpha-position during the racemization of (S)
      1-phenylethanol-OD. These results show that direct carbon-to-carbon hydrogen
      transfer occurs via a metal monohydride for the racemization of chiral secondary
      alcohols and reduction of carbonyl compounds to alcohols. For the isomerization,
      the alpha-deuterium of 3-deuterio-1-octen-3-ol was selectively relocated at the
      beta-position of the corresponding ketones (99% D at the beta-position),
      suggesting the involvement of a 1,4-addition of ruthenium monohydride species to
      the alpha,beta-unsaturated ketone intermediate. The ruthenium monohydride species
      and the alpha,beta-unsaturated ketone would be formed through alcoholate
      formation/beta-elimination. Kinetic studies and kinetic isotope effects show that
      the Ru-H bond cleavage (hydride transfer) is included in the rate-determining
      step.

PMID- 16092144
TI  - Rationally designed, polymeric, extended metal-ciprofloxacin complexes.
AB  - Reactions of the antimicrobial fluoroquinolone ciprofloxacin (cfH) with metal
      salts in the presence of aromatic polycarboxylate ligands or under basic
      conditions produce fourteen new metal-cfH complexes, namely, [Ba2(cf)2(1,4
      bdc)(H2O)2] x H2O (1), [Sr6(cf)6(1,4-bdc)3(H2O)6] x 2H2O (2),
      [M2(cfH)2(bptc)(H2O)2] x 8H2O (M = Mn3 and Cd4), [M(cfH)(1,3-bdc)] (M = Mn5, Co6,
      and Zn7), [Zn2(cfH)4(1,4-bdc)](1,4-bdc) x 13H2O (8), [Ca(cfH)2(1,2-Hbdc)2] x 2H2O
      (9) and [M(cf)2] x 2.5H2O (M = Mn10, Co11, Zn12, Cd13, and Mg14) (1,4-bdc = 1,4
      benzenedicarboxylate, bptc = 3,3',4,4'-benzophenonetetracarboxylate, 1,3-bdc =
      1,3-benzenedicarboxylate, 1,2-bdc = 1,2-benzenedicarboxylate). Their structures
      were determined by single-crystal X-ray diffraction analyses and further
      characterized by elemental analyses, IR spectra, and thermogravimetric analyses.
      The structures of 1 and 2 consist of unique two-dimensional arm-shaped layers.
      Compounds 3 and 4 are isostructural and feature one-dimensional structures formed
      from the interconnection of [M2(cfH)2(H2O)2] dimers with bptc ligands. Compounds
      5-7 are isostructural and contain double-chain-like ribbons constructed from
      [M2(cfH)2(CO2)2] dimers and 1,3-bdc. Compound 8 consists of a pair of
      [Zn(cfH)2]2+ fragments bridged by a 1,4-bdc into a dinuclear dumbbell structure.
      Compound 9 is a neutral monomeric complex. To the best of our knowledge,
      compounds 1-9 are the first examples of metal-quinolone complexes that contain
      aromatic polycarboxylate ligands. Compounds 10-14 are isostructural and exhibit
      interesting two-dimensional rhombic grids featuring large cavities with
      dimensions of 13.6x13.6 A. Up to now, polymeric extended metal-cfH complexes have
      never been reported.

PMID- 16092145
TI  - Ab initio and DFT benchmark study for nucleophilic substitution at carbon (SN2@C)
      and silicon (SN2@Si).
AB  - To obtain a set of consistent benchmark potential energy surfaces (PES) for the
      two archetypal nucleophilic substitution reactions of the chloride anion at
      carbon in chloromethane (S(N)2@C) and at silicon in chlorosilane (S(N)2@Si), we
      have explored these PESes using a hierarchical series of ab initio methods [HF,
      MP2, MP4SDQ, CCSD, CCSD(T)] in combination with a hierarchical series of six
      Gaussian-type basis sets, up to g polarization. Relative energies of stationary
      points are converged to within 0.01 to 0.56 kcal/mol as a function of the basis
      set size. Our best estimate, at CCSD(T)/aug-cc-pVQZ, for the relative energies of
      the [Cl(-), CH(3)Cl] reactant complex, the [Cl-CH(3)-Cl](-) transition state and
      the stable [Cl-SiH(3)-Cl](-) transition complex is -10.42, +2.52, and -27.10
      kcal/mol, respectively. Furthermore, we have investigated the performance for
      these reactions of four popular density functionals, namely, BP86, BLYP, B3LYP,
      and OLYP, in combination with a large doubly polarized Slater-type basis set of
      triple-zeta quality (TZ2P). Best overall agreement with our CCSD(T)/aug-cc-pVQZ
      benchmark is obtained with OLYP and B3LYP. However, OLYP performs better for the
      S(N)2@C overall and central barriers, which it underestimates by 2.65 and 4.05
      kcal/mol, respectively. The other DFT approaches underestimate these barriers by
      some 4.8 (B3LYP) to 9.0 kcal/mol (BLYP).

PMID- 16092146
TI  - Electronic excitations of green fluorescent proteins: protonation states of
      chromophore model compound in solutions.
AB  - Green fluorescent proteins (GFPs) are widely used as tools in biochemistry, cell
      biology, and molecular genetics due to their unusual optical spectroscopic
      characteristics. The spectrophotometric and fluorescence properties of GFPs are
      controlled by the protonation states and possibly cis-trans isomerization of the
      chromophore (p-hydroxybenzylideneimidazolinone). In this work, we have
      investigated electronic structures, liquid structures, and solvent shifts of the
      three possible protonated states (neutral, anionic, and zwitterionic) and their
      cis-trans isomerization of a model compound 4'-hydroxybenzylidene-2-methyl
      imidazolin-5-one-3-acetate (HBMIA) in aqueous solutions. Our calculated results
      suggest that HBMIA could adopt both cis and trans conformations in a solution,
      and it exists in three different protonation states depending on the pH
      conditions. The absorption spectrum observed in neutral solution is thus assigned
      to the electronic excitations within the neutral form and the cis isomer of the
      zwitterionic form, while the absorption band at 425 nm in the basic solution is
      due to the excitations within the anionic form and the trans isomer of the
      zwitterionic form. Some technical problems related to the computation of
      electronic excitations within the HBMIA at the anionic state are also discussed.

PMID- 16092147
TI  - Identification of immunodominant autoantigens in rat autoimmune orchitis.
AB  - Infection and inflammation of the genital tract are amongst the leading causes of
      male infertility. Experimental autoimmune orchitis (EAO) in the rat serves as a
      model for the investigation of inflammatory testicular impairment. In this study,
      experiments were conducted to identify the molecules that are responsible for
      eliciting the autoimmune attack on the testis. EAO was induced in in-bred Wistar
      rats by active immunization with testis homogenates (EAO group I). Development of
      disease was observed using histological techniques and a new non-invasive three
      dimensional (3D) imaging technology for in vivo monitoring, termed flat-panel
      volumetric computed tomography (fpvCT). Examination of control and EAO testes
      demonstrated the superior image quality of high-resolution fpvCT. A proteomics
      approach using 2D SDS-PAGE and immunoblotting analysis with EAO sera identified
      12 spots. Seven were subsequently identified by mass spectrometry as heat shock
      proteins 60 (Hsp60) and 70 (Hsp70), disulphide isomerase ER-60, alpha-1-anti
      trypsin, heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1), sperm outer dense
      fibre major protein 2 (ODF-2), and phosphoglycerate kinase 1. Hsp70, ODF-2, hnRNP
      H1, and ER-60 were identified by all EAO sera studied. To test the capacity of
      the identified proteins to elicit testicular autoimmune disease, recombinant
      proteins were used either individually or in combination to immunize rats (EAO
      group II). In all groups, the incidence of EAO was 25%. Inflammatory-type (ED1+)
      and resident (ED2+) macrophages, lymphocytes (CD45RA+), and dendritic cells (Ox
      62+) were strongly increased in EAO group II animals, comparable to the testes of
      EAO I rats. Pre-immunization with a low dose of recombinant Hsp 70, hnRNP H1 or
      ODF-2 before induction of EAO with testis homogenate significantly delayed the
      onset of EAO but could not prevent disease. The identification of testicular
      autoantigens will allow a better understanding of disease pathogenesis and could
      provide a basis for the development of novel therapies for inflammation-based
      male infertility.

PMID- 16092148
TI  - [Neuromuscular diseases 2: muscular dystrophies (MD)].
AB  - Traditionally, muscular dystrophies (MDs) are progressive, hereditary, and
      primarily degenerative myopathies. Nowadays, due to molecular biology, MDs are
      looked upon as clinically and genetically heterogeneous myopathies characterized
      by protein defects of muscle tissue resulting most often in muscle weakness. They
      are caused by gene mutations leading to a decrease of structural proteins or
      enzymes. The site of the primary defect and the protein function are different.
      The disorders are defined according to the underlying protein defect
      (dystrophinopathy, calpainopathy, and others). The gene or gene product are not
      yet known in all forms of MD (for example, facioscapulohumeral muscular
      dystrophy). Therefore, the nomenclature based on the protein defects and the term
      MD are used concurrently. Clinical symptoms, pathogenesis, diagnosis, therapy,
      prognosis, and possible prevention of the more frequent MDs are discussed:
      dystrophinopathies (Duchenne, Becker type), Emery-Dreifuss syndrome (3 forms),
      facioscapulohumeral MD, limb-girdle MD (17 forms), myotonic dystrophies (2
      forms), and congenital MD (11 forms). This article highlights the significance of
      molecular analyses and the possible multisystemic symptoms in these myopathies.

PMID- 16092149
TI  - Carbon emissions threaten marine species.

PMID- 16092150
TI  - Africa focus raises malaria funds.

PMID- 16092151
TI  - Greg Gibson.

PMID- 16092152
TI  - The focus of desire.

PMID- 16092153
TI  - Does creatinine kinase-MB elevation after percutaneous coronary intervention
      predict outcomes in 2005? Cardiac enzyme elevation after successful percutaneous
      coronary intervention is not an independent predictor of adverse outcomes.

PMID- 16092154
TI  - [Non invasive ventilation: does it complete the range of care in perioperative
      thoracic surgery?].

PMID- 16092155
TI  - [Research is the future of pulmonary medicine. Welcome to the "Journees de
      recherche respiratoire" (J2R)!].

PMID- 16092156
TI  - [Transbronchial needle aspiration. France in the slow lane of Europe!].

PMID- 16092157
TI  - [Art--and artefacts--of exhaled NO measurement in asthma].

PMID- 16092158
TI  - [To be a francophone pneumologist or a pneumologist and francophone?].

PMID- 16092159
TI  - [From lung research to lung health].

PMID- 16092160
TI  - [Assessment of asthma control: an audit of clinical practice].
AB  - INTRODUCTION: Despite the development of international guidelines for the
      management of asthma, epidemiological surveys suggest that control of the disease
      remains poor. In order to investigate clinical practice a postal questionnaire
      was used to study the evaluation of asthma control, the assessment of factors
      associated with poor control and the impact of tools to measure asthma control.
      METHODS: 12,000 questionnaires were mailed to 10,000 general practitioners (GP)
      and 2000 French specialists. RESULTS: The response rate was 13 and 31% for GP and
      specialists respectively. 44% of specialists and 9% of GP's declared that they
      made a systematic assessment of nocturnal symptoms, beta2 agonist usage and peak
      flow. 32% of the specialists and 15% of the GP's declared a systematic search for
      poor compliance, inhaler technique and the avoidance of trigger factors. 77% of
      the GP's and 43% of the specialists had never used a questionnaire for asthma
      control. CONCLUSION: Available tools for the systematic evaluation of asthma
      control are rarely used and both asthma control itself and factors known to be
      associated with it are insufficiently monitored. The impact of the implementation
      in the medical community of a more systematic and pragmatic approach should be
      evaluated.

PMID- 16092161
TI  - [Development of a questionnaire concerning the knowledge of COPD].
AB  - INTRODUCTION: The level of a patient's knowledge about his disease and its
      treatment is an essential part of an educational assessment. It is useful
      therefore to make use of a rapid, easy and valid method to collect the
      information necessary to develop an educational programme adapted to the needs of
      the patient. The aim of this study is to validate, in a structured way, a
      knowledge questionnaire on chronic obstructive pulmonary disease (COPD). METHODS:
      Following a revue of the literature an initial questionnaire was constructed. It
      included of four domaines: biomedical aspects; symptoms and signs of severity;
      general knowledge and treatments. The questionnaire was tested on 35 subjects
      with COPD in order to assess its clarity and comprehensibility. It was reviewed
      and modified in both content and format by 11: French experts. The
      reproducibility was studied by repeat testing. RESULTS: The first version of the
      questionnaire developed by the working party consisted of 50 items. It was
      reduced to 41 items after interviews with 35 COPD patients and evaluation by 11
      experts. The questionnaire appeared to be reproducible: mean concordance 79.5%;
      minimum 53.3%; maximum 100% and intra-class correlation coefficient 0.53.
      CONCLUSION: This study lead to the development of a French language COPD
      knowledge questionnaire.

PMID- 16092162
TI  - [Desensitisation to infliximab in patients with Crohn's disease].
AB  - BACKGROUND: Infliximab is a chimeric monoclonal antibody directed against tumour
      necrosis factor-alpha that has been shown to improve chronic refractory and
      fistulating Crohn's disease. Infliximab infusions have been associated both with
      immediate and delayed reactions. MATERIAL AND METHODS: Desensitisation was
      performed in four patients who had experienced immediate reactions to infliximab
      infusions and in one who had developed a delayed reaction. No therapeutic
      alternatives were available for these patients. Before desensitisation, skin
      tests were performed. RESULTS: Skin-tests were negative for all patients.
      Desensitisation was performed with serial dilutions of infliximab with monitoring
      of vital signs before each increment. After parenteral desensitisation, all five
      patients were able to tolerate infliximab infusion without complications or any
      requirement for antihistamines or steroids. However, two patients who had
      initially presented with an immediate reaction to infliximab experienced
      arthralgia and myalgia similar to a "serum sickness-type" of reaction 6 to 10
      days after desensitisation. CONCLUSION: Even if there is no evidence of an
      allergic mechanism in infusion reactions to infliximab, successful
      desensitization can be achieved for patients experiencing acute reactions. The
      mechanism of desensitisation remains presently unknown. It is not yet possible to
      say if desensitization will be effective in preventing delayed reactions.

PMID- 16092163
TI  - [Economic burden of COPD: the SCOPE study].
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major health
      problem. Few data about COPD economic burden are available. METHODS: SCOPE was an
      observational economical retrospective and prospective study conducted in France
      in 2001, by 114 general practitioners (GPs) and 57 lung specialists. The aim was
      to describe the burden of COPD patients and to estimate the annual cost according
      to severity stages. Health resource utilization was collected by questionnaires
      over a 12-month period for 285 patients. RESULTS: It was a cost-of-illness
      analysis. COPD patients followed by a lung specialist were more severe than
      patients followed by a GP and had a higher level of medical resource consumption.
      The COPD disease and its complications explained 66% of the total cost. The main
      cost drivers were inpatient care (35%, or 1509,9 euros/year/patient) and
      prescription medications (31%, or 1340,6 euros/year/patient). The direct total
      cost varied according to COPD severity on account of inpatient care and
      respiratory assistance. DISCUSSION: This study confirmed the economic burden of
      COPD in France. Actions allowed to slow down the disease's evolution and to
      anticipate the exacerbation could reduce the cost.

PMID- 16092164
TI  - [Chronic pulmonary berylliosis: a model of interaction between environment and
      genetic predisposition (Part 1). Mineralogy, toxicology, epidemiology and risk
      factors].
AB  - INTRODUCTION: The physico-chemical properties of beryllium (Be) are crucial for
      high technology industries. The inhalation of beryllium may cause, in certain
      individuals, a specific sensitisation (BeS) and lead, in some of them, to a
      pulmonary granulomatosis called chronic pulmonary berylliosis (CPB). BACKGROUND:
      Although there is no linear relationship between the level of exposure to Be and
      the risks of BeS and CPB, the highest exposures are associated with an increased
      risk. The specific influences of the chemical composition, the solubility and
      different types of Be on the risk of BeS an CPB are poorly understood. Insoluble
      particles of small diameter are probably associated with an increased risk. Many
      studies have reported the role of a genetic predisposition in the risk of BeS and
      CPB. At present the role of HLA-DPB1 Glu69 in sensitisation to Be is the best
      studied. CONCLUSION: Sensitisation to Be and CPB result from the combination of
      exposure and predisposing genetic polymorphisms. CPB is a model for the
      understanding of the pathology of certain ideopathic pulmonary granulomatoses
      such as sarcoidosis.

PMID- 16092165
TI  - [Chronic beryllium disease: a model of interaction between environmental exposure
      and genetic predisposition. Pathogenesis and clinical features (Part 2)].
AB  - INTRODUCTION: Chronic beryllium disease (CBD) is an occupational lung disease
      caused by the inhalation of beryllium dust, fumes or metallic salts. CURRENT
      DATA: Beryllium affects the lungs via particles deposited in the pulmonary
      alveoli. These are ingested by alveolar macrophages which act as antigen
      presenting cells to CD4+ T lymphocytes. T lymphocytes proliferate in response to
      beryllium antigens and combined with macrophages produce numerous epithelioid
      granulomas with the release of inflammatory cytokines (IFNgamma, IL-2, TNFalpha
      and IL6) and growth factors. Beryllium induces macrophage apoptosis which reduces
      its clearance from the lung which in turn contributes to the host's continual re
      exposure and thus a chronic granulomatous disorder. Pulmonary granulomatous
      inflammation is the primary manifestation of CBD, but the disease occasionally
      involves other organs such as the liver, spleen, lymph nodes and bone marrow. The
      clinical, radiological, and histopathological features of CBD can be difficult to
      distinguish from sarcoidosis. The Beryllium lymphocyte proliferation test (BeLPT)
      demonstrates a beryllium specific immune response, confirms the diagnosis of CBD,
      and excludes sarcoidosis. CONCLUSIONS AND PERSPECTIVES: CBD provides a human
      model of pulmonary granulomatous disease produced by an occupational exposure,
      occurring more frequently in those with a genetic pre-disposition. It can be
      differentiated from sarcoidosis by specific immunological testing.

PMID- 16092166
TI  - [Domiciliary non-invasive ventilation in children].
AB  - INTRODUCTION: Non-invasive positive pressure ventilation (NPPV) represents a
      particularly interesting technique of ventilatory support in paediatrics. Indeed,
      a significant number of pathologies that may be responsible for chronic
      respiratory insufficiency in childhood, such as neuromuscular diseases,
      obstruction of the upper airways, disorders of chest wall and/or the lungs, and
      disorders of ventilatory control may all lead to alveolar hypoventilation that
      can be improved by ventilatory support. BACKGROUND: Few physiological studies
      have been performed on NPPV in children. The most appropriate modes and settings
      for each pathology have not been clearly defined, and the criteria for commencing
      NPPV are based essentially on consensus guidelines for the management of
      neuromuscular disorders. VIEWPOINT: All the health care professionals managing
      these children should combine their efforts to evaluate more precisely the medium
      and long-term physiological effects of NPPV on the respiratory muscles, the
      development of the respiratory system, inspiratory activity, the indications for
      starting treatment and, above all, the benefits in terms of psycho-neurological
      development and quality of life. CONCLUSIONS: A better evaluation of the medium
      and long-term physiological and psychological benefits together with technical
      improvements in ventilators and associated equipment should allow a rapid
      expansion in the use of domiciliary NPPV in children.

PMID- 16092167
TI  - [T regulatory lymphocytes, atopy and asthma: a new concept in three dimensions].
AB  - BACKGROUND: Allergic inflammation is considered to be the result of a pattern of
      Th2 lymphocyte activation. However this inflammation, relevant for atopy and
      infiltration of affected tissues by eosinophils, is insufficient by itself to
      explain the clinical features of asthma. Several studies have demonstrated that
      Th2 type inflammation was also associated in asthma with a Th1 response, with
      production of gamma interferon. It has recently been shown that the regulatory T
      lymphocytes (Treg) which produce IL-10 and/or TGF-beta and induce tolerance are
      defective in allergic patients. In addition, these lymphocytes increase during
      specific immunotherapy. Their decrease could explain the Th2 activation found in
      atopic patients. PERSPECTIVE: We review the potential importance of Treg cells in
      atopy and also asthma, and propose a concept whereby the allergic inflammatory
      response would not be due to a Th1/Th2 imbalance, but rather to a Treg deficiency
      progressively rising from normal to atopic, from atopy to asthma and from asthma
      to acute exacerbations. CONCLUSION: Three dimensions of inflammation need
      therefore to be taken into account: Th1, Th2 and Treg.

PMID- 16092168
TI  - [An unusual cause of pulmonary cysts].
AB  - INTRODUCTION: Multiple pathologies may be associated with cystic appearances in
      the lungs. Lymphangioleiomyomatosis, Langerhans cell histiocytosis and
      lymphocytic interstitial pneumonia are the principal causes of thin walled
      pulmonary cysts. CASE REPORT: We report the case of a non-smoking woman of 71
      years, a retired farmer, who was admitted on account of cough, increasing
      dyspnoea, fever and loss of weight that developed following exposure to hay. The
      thoracic CT scan revealed diffuse ground glass opacities and centrilobular
      nodules. Multiple thin walled cystic shadows were distributed homogeneously
      throughout both lung fields. Broncho-alveolar lavage revealed a marked
      lymphocytosis (63%) and precipitins for Microsporum Faeni were strongly positive
      (6 arcs). The respiratory symptoms resolved spontaneously during the stay in
      hospital, allowing the patient to be discharged after 3 weeks with the advice to
      avoid all contact with hay. One month later she remained symptom free, the repeat
      CT scan showed a diminution ofthe ground glass opacities and the nodules but
      persistence of the pulmonary cysts. CONCLUSION: The diagnosis of hypersensitivity
      pneumonitis should be considered in the presence of a diffuse pulmonary
      infiltrate with multiple thin walled cysts in a patient with a suggestive history
      and clinical picture.

PMID- 16092169
TI  - [Use of 153Sm-EDTMP to relieve pain from bone metastasis in lung cancer].
AB  - INTRODUCTION: The treatment of bone metastasis from lung cancer is palliative in
      nature with elimination of pain being the primary goal. Management is based on
      pharmacologicalmethods (steroids, morphine, and pamidronate) and radiotherapy.
      However, other treatments have been developed including the systemic
      radiopharmaceutical 153Sm-EDTMP. CASE REPORTS: We report data from 6 lung cancer
      patients with bone metastases treated with 153Sm-EDTMP. Demographic and
      therapeutic data, pain evaluation by visual analogue scale (VAS) and change in
      opioid analgesia requirements (expressed as intravenous morphine equivalent) as
      well as survival were studied. Pain associated with bone metastasis (median VAS =
      8 [7-9], median morphine dose = 167 mg [100-800 mg]) did not significantly
      improve (median VAS after 153Sm-EDTMP = 8.5 [5-10], median morphine dose after
      153Sm-EDTMP = 185 mg [30-2 200 mg]) in this group of patients. CONCLUSION: Our
      results combined with current data in the literature concerning the use of this
      treatment in the treatment of bone pain associated with metastatic lung cancer
      suggest that at present its use cannot be recommended outside the context of
      clinical of clinical trials.

PMID- 16092170
TI  - [Increase in right-to-left intracardiac shunt with non-invasive ventilation].
AB  - INTRODUCTION: Hypoxia caused by an increase in right-to-left shunt has been
      reported in patients with patent foramen ovale treated with levels of positive
      end-expiratory pressures (PEEP) greater than 10 cmH2O. This phenomenon has not
      previously been described with non-invasive ventilation (NIV). CASE REPORT: A 23
      year-old man with tetralogy of Fallot and a severe kyphoscoliosis was admitted at
      the hospital for chronic dyspnoea. Arterial blood gases on room air: pH 7.43,
      PaCO2 39 mmHg, PaO2 67 mmHg, HCO3- 25 mmol/l, SaO2 95%. Nocturnal oxymetry showed
      severe hypoxaemia resistant to oxygen. NIV with PEEP of 3 cm H2O was commenced.
      With ventilation, his oxygenation worsened. An echocardiogram performed during
      NIV showed an increase in the right-to-left interventricular gradient from 22 to
      37 cmH2O, and of the right ventriculo-auricular gradient from 76 to 142 mmHg.
      Furthermore, his oxygen saturation decreased progressively from 95 to 85%.
      Following removal of NIV, the patient recovered in 15 minutes. DISCUSSION: We
      report an increased right-to-left intracardiac shunt in a patient with tetralogy
      of Fallot. Compression of pulmonary vessels and cardiac cavities induced by NIV
      may have been enhanced by a reduction in thoracic compliance related to
      kyphoscoliosis. Right-to-left shunt in patients with kyphoscoliosis may be a
      contra-indication to NIV.

PMID- 16092171
TI  - [Paraneoplastic nephrotic syndrome associated with broncho-pulmonary cancer].
AB  - INTRODUCTION: Paraneoplastic nephrotic syndrome associated with malignant broncho
      pulmonary tumors. Three cases and literature review. Malignant broncho-pulmonary
      tumours are the principal cause of a paraneoplastic nephrotic syndrome. These
      tumours are most often small cell or squamous bronchial carcinomas. In 75% of
      cases the nephrotic syndrome is due to a membranous glomerulonephritis and it
      usually precedes the discovery of the causative tumour. CASES REPORT: Three cases
      of paraneoploastic nephrotic syndrome associated with bronchial carcinoma are
      described. The first is of a bronchial carcinoid tumour associated with a
      membrano-proliferative glomerulonephritis. In the second a bronchial
      adenocarcinoma was revealed by a membranous glomerulonephritis. The last case
      concerns a squamous carcinoma associated with a nephrotic syndrome in which the
      histological lesions were not documented on account of progression to rapidly
      fatal acute renal failure. CONCLUSION: A revue of the literature describes the
      associations between paraneoplastic nephrotic syndrome and bronchial carcinoma.

PMID- 16092172
TI  - [Recurrent aspiration pneumonia after a gastric banding for treatment of
      obesity].

PMID- 16092173
TI  - [Survival analysis: how to manage censored data? The Kaplan-Meier's method].

PMID- 16092174
TI  - [Recent advances in the assessment of respiratory muscle endurance: (1999-2004)].

PMID- 16092175
TI  - [Transbronchial needle aspiration during flexible fibroscopy].

PMID- 16092176
TI  - Healthy eating. Spectacular soy. Easy to cook, tasty to eat.

PMID- 16092177
TI  - Sleep apnea and diabetes.

PMID- 16092178
TI  - Forearm glucose checks may miss lows.

PMID- 16092179
TI  - The joy of chocolate.

PMID- 16092180
TI  - Diabetes basics. Complications. An introduction.

PMID- 16092181
TI  - The heart of a woman.

PMID- 16092182
TI  - A heart on fire.

PMID- 16092183
TI  - What works. What doesn't. Evidence-based medicine helps your doctor decide which
      treatments are best for you.

PMID- 16092184
TI  - Back from Iraq. A soldier's story.

PMID- 16092185
TI  - Tackling type 2 in kids. A new study aims to find the best treatment for children
      with the disease.

PMID- 16092186
TI  - Go fourth! Welcome to our Fourth of July picnic.

PMID- 16092187
TI  - The "hidden story" of Bill C-54: the Personal Information Protection and
      Electronic Documents Act and health information.

PMID- 16092188
TI  - Forty years after ... Medicare and Medicaid by the numbers.

PMID- 16092189
TI  - Seeing red: Americans driven into debt by medical bills. Results from a National
      Survey.
AB  - New analysis of the 2003 Commonwealth Fund Biennial Health Insurance Survey
      reveals that an estimated 77 million Americans age 19 and older--nearly two of
      five (37%) adults--have difficulty paying medical bills, have accrued medical
      debt, or both. Working-age adults incur significantly higher rates of medical
      bill and debt problems than adults 65 and older, with rates highest among the
      uninsured. Even working-age adults who are continually insured have problems
      paying their medical bills and have medical debt. Unpaid medical bills and
      medical debt can limit access to health care: two-thirds of people with a medical
      bill or debt problem went without needed care because of cost--nearly three times
      the rate of those without these financial problems.

PMID- 16092190
TI  - [Studies of acidic degradation of heparin. A UV-VIS spectroscopy study].
AB  - The preliminary studies on acidic degradation of heparin were performed. The UV
      VIS and 1H-NMR techniques were used. The analogical features of degradation
      products of heparin, glucuronic acid and furfural were found (7 characteristic
      groups).

PMID- 16092191
TI  - [Hydrolysis of keratin products using some of sulfonic acids. Isolation of
      hydrolysing factors from hydrolyzates].
AB  - The term of isolation of arylosulfonic acids as hydrolysing factors from casein's
      hydrolyzates have been worked out. The most satisfactory results have been
      achieved when using in this case chloride 2,3,5-triphenylo-2H-tetrazole. When
      using benzenosulfonic acid as the best hydrolising factor 98.4% of this acid was
      removed from hydrolysates of hoofs whereas 96.1% was removed from hydrolysates of
      bristles. The residues of acids remaining in hydrolysates have been removed by
      shaking with Wofatyt SBW in form H+. The total recovery of aminoacids
      irrespectively to kind of hydrolyzate and applied acid amounts to 95.5% average.

PMID- 16092192
TI  - [High-performance liquid chromatographic determination of propanidid and
      etomidate].
AB  - High-performance reversed-phase liquid chromatographic determination of
      propanidid and etomidate was performed on ODS silica, after precipitation of the
      proteins in plasma with methanol, extraction of the drugs with diethyl ether,
      evaporation and dissolving in a mobile phase: acetonitrile-phosphate buffer pH
      4.44 (7:3, v/v); UV detection at 254 nm. Dionine hydrochloride was used as an
      internal standard. Propanidid was determined in a range 5-25 microg/cm3 of plasma
      and etomidate in 0.1-0.5 microg/cm3 of plasma, thus enables the analysis of
      therapeutic levels of the drugs.

PMID- 16092193
TI  - [Propanidid and etomidate identification from the blood by thin-layer
      chromatography].
AB  - Propanidid and etomidate were extracted from blood with diethyl ether at pH ca. 8
      (phosphate buffer), then separated and identified by thin-layer chromatography on
      silica gel, using diethyl ether-acetone (3:1, v/v) for propanidid or dioxane
      acetic acid (47:3, v/v) for etomidate as the mobile phase. Both compounds can be
      revealed on dried chromatograms using sodium carbonate solution up to the amount
      1 microg/cm3 of plasma, and it is sufficient sensivity for propanidid adhibited
      in therapeutic doses, whereas this limits the detection of etomidate for
      overdosed patients only.

PMID- 16092194
TI  - [Determination of a chlorinated pesticides residue in propolis extract].
AB  - On the basis of gas chromatography in 16 samples of the propolis extract (EEP) a
      residue of chlorinated pesticides were determined. In all investigated samples a
      presence of the pesticides was detected. In the analysed material a lever of HCH
      and DDT is low. Among the propolis samples, collected from different places in
      Bydgoszcz and Torun environs the differences were not found.

PMID- 16092195
TI  - [Interaction between papaverine hydrochloride and antacids].
AB  - The interactions between papaverine hydrochloride and antacids and sucralfate was
      studied.

PMID- 16092196
TI  - [The catalytic rate constant. Effect of acetone on acidic hydrolysis of ester
      cyclohexyl acidacetylomethyl (AmMC)].
AB  - The catalytic rate constants k(HCl) were established for hydrolysis of beta
      lactam moiety in AmMC using equation k(obs) = k(H2O) + k(HCl)[HCl]. The estimate
      the effect of aceton the relation log k(HCl) = log kD + k Z(mu)/D was applied.
      The rate constant increases with the decrease of dielectric constant of the
      solvent.

PMID- 16092197
TI  - [Effect of 5-fluorouracil on DNA synthesis, mitotic index and spleen cells in
      mice after syngeneic bone marrow transplantation].
AB  - The effects of 5-fluorouracil (5-FU) on DNA synthesis, mitotic index and cell
      composition of mouse spleens after 6 Gy X rays irradiation of mice and syngenic
      bone marrow transplantation were investigated. One dose of 5-FU (100 mg/kg body
      weight) administered 16 hrs after bone marrow transplantation reduced mitotic
      index and development of bone marrow grafts, but did not inhibit incorporation of
      3H-thymidine into DNA. It correlates with high thymidylate synthase activity
      previously noted in the same model. Also the increased number of cells from
      lineage of erythroblasts correlates with high DNA synthesis and thymidylate
      synthase activity indicating, probably, the presence in those cell lines, the
      cells with high thymidylate synthase content, resistant to 5-FU.

PMID- 16092198
TI  - [Synthesis and analysis of N-acetyl-tyrosine-PAB].
AB  - N-Acetyl-tyrosine-PAB has been synthesised. The results of elementary analysis,
      IR spectrum and physico-chemical properties are presented. A few methods for
      determination of N-acetyl-tyrosine-PAB have been elaborated.

PMID- 16092199
TI  - [Investigations of pyrazine derivatives. Part XXVII. Synthesis and
      tuberculostatic activity of some 6-alkoxypyrazine-2-carbotioamids].
AB  - It was found that reaction of sodium alcoholates and cyanopyrazine yields
      alkoxypyrazine-nitriles. In heterogenic reaction both 2-alkylimidesters-6
      chloropyrazine or 2-alkylimidoesters-6-alkoxypyrazine can be obtained dependent.
      This is dependent on quantity of alcohol used for reaction. Final products,
      alkoxypyrazinethioamides were tested for tuberculostatic activity (MIC within 31
      500 mcg/cm3).

PMID- 16092200
TI  - [Study of the synthesis of pyrazine derivates. Part XXVIII. Reaction of
      pyrazineamide with CS-2].
AB  - The synthesis of pyrazine derivatives, e.g. 1,3,4-thiodiazole (I, III-V, XII),
      1,2,4-triazole (II) and N-substituted amidrazones is reported.

PMID- 16092201
TI  - [Synthesis of 4,4-substituted-5,5-mercapto-3,3'-bi-1,2,4-triazole and 2,2'-amino
      substituted-5,5-bi-1,3,4-thiodiazole].
AB  - In reaction of oxalic acid dihydrazide with isothiocyanates were obtained the
      respective thiosemicarbaside derivatives (Ia-IXa). Their cyclization in alkaline
      media have given the corresponding 4,4'-substituted-5,5'-mercapto-3,3'-bi-1,2,4
      triazole (Ib-IXb), in acidic media however were formed the 2,2'-amino-substituted
      5,5'-bi-1,3,4-thiodiazole (Ic-VIIIc).

PMID- 16092202
TI  - [Thiadiazolidines derivates as analytical reactants. Part XI. Synthesis and
      analytical properties of ATIDAREZ-beta and ATIDAREZ-gamma].
AB  - New complex-forming azodyes were synthesized: 2-amine-5-(2',4'-dihydroxy-5'
      carboxyphenylazo-1')-1,3,4-thiadiazol (ATIDAREZ-beta) and 2-amine-5-(2',4'
      dihydroxy-3-carboxyphenylazo-1')-1,3,4-thiadiazol (ATIDAREZ-gamma). Absorbance
      maximum of methanol solution occurs at lambda = 230 and 440 nm and the molar
      absorbance coefficient E(lambdamax) = 8000 and 25,000, respectively (ATIDAREZ
      beta); lambda = 240 and 440 nm and E(lambdamax) = 10,200 and 21,600, respectively
      (ATIDAREZ-gamma). The determined dissociation constants--higher values for
      ATIDAREZ-gamma than for ATIDAREZ-beta--indicate a stronger interaction of -OH and
      -COOH group positioned (to ortho -COOH) side by side (of spectra IR analysis)-
      intra- and intermolecular hydrogen bonds (association). In reaction with metal
      ions the formation of chelate compounds with Fe3+, Fe2+, Co2+, Ni2+, Cu2+ was
      stated for ATIDAREZ-beta; Co2+, Cu2+ and Ni2+ with ATIDAREZ-gamma at the L:M
      molar ratio of 1:1, when M = Cu2+ (for ATIDAREZ-beta and gamma) and M = Ni2+ (for
      ATIDAREZ-gamma) or 2:1 for Co2+, Fe2+, Fe3+ and Ni2+ (ATIDAREZ-beta) and Co2+
      (ATIDAREZ-gamma). ATIDAREZ-gamma complexes with Co2+ and Cu2+ and Ni2+ are more
      stable than that of ATIDAREZ-beta (except Ni2+ complex). The obtained results of
      determinations were compared with that of azodyes of the following series: 2
      amine-1,3,4-thiadiazole (ATIDAN, ATIDAN-6S, ATIDAK, ATIDAR, ATIDAP), 1,3,4
      thiadiazole (TIDAREZ-beta and gamma), benzimidazole (BIAREZ-beta and gamma).

PMID- 16092203
TI  - [Synthesis of new 4'-[4-(N2-methyl-2-phenyl)-N1-ethyldiamine]-butyrophenones.
      Laboratory notes].
AB  - The synthesis of some 4'-[4-(N2-methyl-2-phenyl)-N1-ethyldiamine]-buthyrophenones
      as intermediates for variety of buthyrophenones is described.

PMID- 16092204
TI  - [Synthesis of some 4-nitrophenylfuran derivates analogs of Dantrolene].
AB  - Six new phenacylidene derivatives of 5-(4-nitrophenyl)furan were obtained by
      reacting 5-(nitrophenyl)furfural with 4 substituted acetophenones.

PMID- 16092205
TI  - [Synthesis of radiosensitizers. Part VII. Synthesis of 3-bromo-4-chlorophenacyl
      alkylxanthates].
AB  - In the frame-work of search for new potential radiosensitizers a series novel 3
      bromo-4-chlorophenacyl alkylxanthates were synthetized by reacting 3-bromo-4
      chlorophenacyl bromide with potassium alkylxanthates, in which allyl, ethyl,
      propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl, heptyl, octyl,
      isooctyl, decyl, 3-tetrahydrofurfuryl, benzyl, phenylethyl and phenylpropyl
      constituted the alkyl group.

PMID- 16092206
TI  - [Derivates of 1,1-dioxo-1,4,2-benzoditiazines. Part XII. Synthesis and
      pharmacology of some 6-chloro-3-carboxyalkylamino-7-methyl-1,1-dioxo-1,4,2
      benzodithiazines].
AB  - Preparation of some novel 6-chloro-3-carboxyalkylamino-7-methyl-1,1-dioxo-1,4,2
      benzodithiazines (I-V) and its sodium salts (Ia, IVa) have been elaborated. Their
      chemical structures have been confirmed by elemental analysis, IR and 1H-NMR
      spectrometry. In preliminary pharmacological examination compounds I, Ia, IV and
      IVa exhibited low acute toxicity, moreover investigated compounds shown
      hypertensive and cholagogic activity (I, Ia) and also hypotensive (IV, IVa) or
      diuretic (Ia, IVa) activity, on the other hand above mentioned compounds didn't
      exhibit antiarrhythmic activity. Some relationships between the chemical
      structure and pharmacological activity of the investigated compounds have also
      been discussed.

PMID- 16092207
TI  - [Derivates of 2-mercaptobenzenesulphonamids. Part V. Synthesis of new 1,3-dialkyl
      2-(4-chloro-2-mercapto-5-R-benzenesulphonyl)guanidines].
AB  - Reactions of 3-methylthio, 3-mercapto and 3-alkylamino-6-chloro-7-R1-1,1-dioxo
      1,4,2-benzodithiazines (Ia-b, IIa, IIIa-e and IVa-b) with amines were
      investigated. Respective 1,3-dialkyl-2-(4-chloro-2-mercapto-5-R1
      benzenesulphonyl)guanidines possessing equal (Va-i) or unequal (VIa-c) alkyl
      substituents at the 1,3-positions were obtained. Some observations regarding the
      influence of molar ratio, as well the kind of amines used on the course of
      reactions were presented. Finally, the probable mechanisms of these reactions
      were discussed.

PMID- 16092209
TI  - The conundrum of too much information.

PMID- 16092208
TI  - [Biological activity of caffeic acid and its derivates].

PMID- 16092210
TI  - Sleep clinics: treating the exhausted.

PMID- 16092211
TI  - The sleep debate--should doctors be well trained or well rested?

PMID- 16092212
TI  - Loss prevention case of the month--Obsessed with family history.

PMID- 16092213
TI  - Physicians Health Program message--Playing "Russian roulette' with inhalants, pt.
      I.

PMID- 16092215
TI  - Create wealth and minimize taxes with AGP program.

PMID- 16092214
TI  - The goose that laid the golden capsule, part II.

PMID- 16092216
TI  - Trauma rounds--Tennessee Trauma Care System Plan, part IV.

PMID- 16092217
TI  - Department of Health report--Advancing HIV prevention: HIV testing as part of
      regular medical care services.

PMID- 16092218
TI  - Design of dispersion-compensating Bragg fiber with an ultrahigh figure of merit.
AB  - We report a novel idea for achieving highly efficient dispersion-compensating
      Bragg fiber by exploiting a modified quarter-wave stack condition. Our Bragg
      fiber yielded an average dispersion of approximately -1800 ps/(nm km) across the
      C band for the fundamental TE mode and an ultrahigh figure of merit of
      approximately 180,000 ps/(nm dB), which is at least 2 orders of magnitude higher
      than that of conventional dispersion-compensating fibers. The proposed
      methodology could be adopted for the design of a dispersion compensator across
      any desired wavelength range.

PMID- 16092219
TI  - Improved air-silica photonic crystal with a triangular airhole arrangement for
      hollow-core photonic bandgap fiber design.
AB  - We propose an improved photonic crystal (PC) cladding design for existing air
      guiding photonic bandgap (PBG) fibers whose cladding airholes are arranged in a
      triangular lattice pattern. By increasing the sizes of concentrated silica
      regions in the cladding PC, we can have a larger degree of freedom in controlling
      the cladding bandgap regions. We predict that a fiber made from this type of
      cladding would perform better in terms of the PBG-guiding wavelength range,
      radiation loss owing to finite cladding size, and the ability to avoid surface
      mode problems.

PMID- 16092220
TI  - Demonstration of a passive subpicostrain fiber strain sensor.
AB  - We demonstrate a fiber Fabry-Perot (FFP) sensor that is capable of detecting
      subpicostrain signals, from 100 Hz and extending beyond 100 kHz, using the Pound
      Drever-Hall (PDH) frequency locking technique. A low-power diode laser at 1550 nm
      is locked to a free-space reference cavity to suppress its free-running frequency
      noise, thereby stabilizing the laser. The stabilized laser is then used to
      interrogate a FFP sensor whose PDH error signal yields the instantaneous fiber
      strain.

PMID- 16092221
TI  - Observation of spatial migration of excitation in Er-doped optical fibers by
      means of a population grating technique.
AB  - The influence of spatial migration of excitation among neighboring Er3+ ions on
      the dynamics of population grating formation in Er-doped optical fibers is
      reported. The effect manifests itself in an additional increment in the grating
      formation rate compared with the fluorescence growth rate observed for the same
      spatially uniform average light power. The experiments, performed at lambda=1549
      nm in the configuration of transient two-wave mixing with two similar single-mode
      Er-doped fibers with significantly different erbium concentrations (approximately
      640 and approximately 5600 parts in 10(6)), demonstrated the essential
      contribution of this effect to the grating formation rate in the latter fiber.
      The evaluated diffusion coefficient proved to be approximately 2.3 x 10(-9)
      cm2/s, which ensures effective migration of the excitation by approximately 48
      nm, i.e., by approximately 18 average inter-ion distances in this fiber.

PMID- 16092222
TI  - Core-clad silver halide fibers with few modes and a broad transmission in the mid
      infrared.
AB  - There is interest in single-mode fibers that are highly transparent in the mid
      infrared. Such fibers would be valuable for spectroscopy, interferometry, and
      heterodyne detection. We have developed core-clad fibers made of crystalline
      silver halides with an external diameter of 900 microm and core diameters as
      small as 60 microm. These fibers exhibit homogeneous core and cladding regions,
      round cores, and smooth core-cladding interfaces. The 60 microm fibers support
      roughly 70 modes and have low losses over a broad spectral range in the mid
      infrared. This will pave the road for the development of single-mode mid-infrared
      fibers. ie ty of America

PMID- 16092223
TI  - Four-wave mixing with large stokes shifts in heavily Ge-doped silica fibers.
AB  - Four-wave mixing (FWM) in nonlinear germanosilicate fibers with GeO2
      concentrations as high as 67 mol.% in the core is studied theoretically and
      experimentally. Large frequency shifts of 1875-3829 cm(-1) are observed in the
      mixed-mode pump parametric process. The dependence of FWM phase matching on the
      GeO2 concentration, core diameter, and index profile is demonstrated. The 2.5%
      conversion efficiency of an 887 nm signal to a 1.3 microm communication band is
      obtained at a 2 W cw pump power inside the fiber.

PMID- 16092224
TI  - Measurement of the frequency response of a diaphragm-based pressure sensor by use
      of a pulsed excimer laser.
AB  - We present a novel method for measuring the frequency response of a diaphragm
      based optical fiber Fabry-Perot interferometric pressure sensor. The impulse
      response of the sensor to the radiation pressure generated by an excimer laser
      pulse is measured. The Fourier transform of the impulse response yields the
      frequency response of the pressure sensor. Experimental results show that it is a
      convenient and efficient method for measurement of the frequency response of
      diaphragm-based pressure sensors.

PMID- 16092225
TI  - Extended continuous-wave supercontinuum generation in a low-water-loss holey
      fiber.
AB  - We report on the development of a 2.5 microm core photonic crystal fiber with a
      substantially reduced water-peak loss around 1.38 microm, which allows extended
      Raman-soliton supercontinuum generation up to 1.55 microm with a cw ytterbium
      fiber laser pump source. The resulting broadband, high-spectral-power-density,
      low-coherence light source can be employed for advanced, submicrometer resolution
      optical coherence tomography.

PMID- 16092226
TI  - Depth-resolved holographic imaging through scattering media by use of a
      photorefractive polymer composite device in the near infrared.
AB  - We report full-field depth-resolved holographic imaging through scattering media
      by use of a photorefractive polymer device in the near infrared. Real-time images
      through seven scattering mean free paths are acquired in a few seconds with a
      broadband superluminescent diode at 794 nm. A depth resolution of 15 microm and a
      transverse resolution of better than 42 microm are achieved. The photorefractive
      devices used are based on a poly(N-vinylcarbazole):2,4,7-trinitro-9-fluorenone
      dimalenitrile charge-transport network doped with the electro-optic chromophore 1
      (2'-ethylhexyloxy)-2,5-dimethyl-4-(4"-nitrophenylazo)benzene.

PMID- 16092227
TI  - Implementation of optical associative memory by a computer-generated hologram
      with a novel thresholding scheme.
AB  - An associative memory based on a model by Rizvi and Zubairy [Appl. Opt. 33, 3642
      (1994)] is experimentally demonstrated. The parallel optical interconnection is
      realized compactly by computer-generated holograms. A novel scheme of real-time
      thresholding is proposed and is proved to be effective and simple to implement.
      Stored images are successfully retrieved with both complete and partial inputs.

PMID- 16092228
TI  - Characterization of microholograms recorded in a thermoplastic medium for three
      dimensional optical data storage.
AB  - A three-dimensional optical data storage system that combines a new recording
      material with a microholographic data format in which data are stored as single
      bit microholograms is presented. This format offers less sensitivity to
      environmental conditions than the page-based holographic approach in addition to
      an increased compatibility with current storage technologies. The new recording
      material is based on a thermoplastic material. The results presented indicate
      that the dimensions of the microholograms are larger than those calculated by use
      of simple laser beam waist approximations and that multiple layers of
      microholograms would significantly affect signal levels. Data densities
      achievable with the microholographic format will likely be limited by those
      effects.

PMID- 16092229
TI  - Polarization gratings in twisted-nematic liquid-crystal composites doped with
      azobenzene dye.
AB  - Highly efficient and functionalized polarization gratings have been recorded in
      azobenzene-containing mesogenic composites with twisted nematic cell
      configurations. The polarization gratings formed in azobenzene-containing
      mesogenic composites show a high diffraction efficiency of more than 45% and
      convert the polarization state of light at the same time. The polarization
      direction of the diffracted laser beams can be controlled by the twisted angle of
      the nematic cell. These characteristics of the polarization gratings are well
      explained by means of Jones calculus.

PMID- 16092230
TI  - Spiral interferometry.
AB  - We present a surprising modification of optical interferometry. A so-called
      spiral phase element in the beam path of a standard microscope results in an
      interferogram of phase samples, for which the interference fringes have the shape
      of spirals instead of closed contour lines as in traditional interferograms. This
      configuration overrides the basic problem of interferometry, i.e., that
      elevations and depressions cannot be distinguished. Therefore a complete sample
      profile can be reconstructed from a single exposure, promising, e.g., high-speed
      metrology with a single laser pulse. The method is easy to implement, it does not
      require a spatially separated reference beam, and it is optimally stable against
      environmental noise.

PMID- 16092231
TI  - Strong optical force induced by morphology-dependent resonances.
AB  - We consider the resonant optical force acting on a pair of transparent
      microspheres by the excitation of morphology-dependent resonance (MDR). The
      bonding and antibonding modes of the MDR correspond to strong attraction and
      repulsion, respectively. The dependence of the force on separation and the role
      of absorption are discussed. At resonance, the force can be enhanced by orders of
      magnitude such that it will dominate other relevant forces. We found that a
      stable binding configuration can be induced by the resonant optical force.

PMID- 16092232
TI  - Transverse mode coupling in an optical resonator.
AB  - Small-angle scattering due to mirror surface roughness is shown to couple the
      optical modes and deform the transmission spectra in a frequency-degenerate
      optical cavity. A simple model based on a random scattering matrix clearly
      visualizes the mixing and avoided crossings between multiple transverse modes.
      These effects are visible only in the frequency-domain spectra; cavity ringdown
      experiments are unaffected by changes in the spatial coherence, as they probe
      just the intracavity photon lifetime.

PMID- 16092233
TI  - Coherent combining in an Yb-doped double-core fiber laser.
AB  - Coherent combining is demonstrated in a clad-pumped Yb-doped double-core fiber
      laser. A slope efficiency of more than 70% is achieved with 96% of the total
      output power in the fundamental mode of one of the two cores. This high combining
      efficiency is obtained when both cores are coupled via a biconical fused taper in
      a Michelson interferometer configuration.

PMID- 16092234
TI  - Three-dimensional vision with dual acousto-optic deflection encoding.
AB  - We report a new method of sensing a three-dimensional (3D) object surface with an
      arbitrary geometric shape. In this approach, the first-order beams diffracted
      from two acousto-optic deflectors (AODs) interfere with each other to form a
      spatial carrier that is used to encode the depth information from the 3D object
      surface. A direct digital synthesizer is utilized to control two AODs to generate
      sequentially spatial carriers with different spatial frequencies so that a
      modified temporal phase-unwrapping technique can be applied for decoding the
      shape information of the test surface. Preliminary experimental results are
      presented to demonstrate the effectiveness of this method.

PMID- 16092235
TI  - Spectral priors improve near-infrared diffuse tomography more than spatial
      priors.
AB  - We compare the benefits of spatial and spectral priors in near-infrared diffuse
      tomography image reconstruction. Although previous studies that incorporated
      anatomical spatial priors have shown improvement in algorithm convergence and
      resolution, our results indicate that functional parameter quantification by this
      approach can be suboptimal. The incorporation of a priori spectral information
      significantly improves the accuracy observed in recovered images. Specifically,
      phantom results show that the maximum total hemoglobin concentration ([Hb(T)]) in
      a region of heterogeneity reached 91% of the true value compared to 63% using
      spatial priors. The combination of both priors produced results accurate to 98%
      of the true [Hb(T)]. When both spatial and spectral priors were applied in a
      healthy volunteer, glandular tissue showed a higher [Hb(T)], water fraction, and
      scattering power compared to adipose tissue.

PMID- 16092236
TI  - Phase matching, quasi-phase matching, and pulse compression in a single waveguide
      for enhanced high-harmonic generation.
AB  - We demonstrate, for the first time to our knowledge, that the efficient region of
      high-harmonic generation can be shifted from lower to higher photon energies by
      combining phase matching, quasi-phase matching, and pulse compression in a single
      gas-filled waveguide. An intrawaveguide pulse compression process that works
      through a combination of ionization-induced refraction and guiding shortens the
      laser pulse as it propagates through an Ar-filled waveguide. This leads to
      enhanced harmonic emission at high photon energies near 95 eV while it reduces
      emission at low photon energies near 45 eV. The waveguide geometry also mitigates
      ionization-induced refraction, allowing Ar gas with high effective nonlinear
      susceptibility to be used.

PMID- 16092237
TI  - High-power optical parametric chirped-pulse amplifier system with a 1.55 microm
      signal and a 1.064 microm pump.
AB  - We have designed and built a chirped-pulse parametric-amplifier system that
      utilizes a 10 Hz, 300 ps, Nd:YAG pump laser system; a 1.575 microm fiber
      oscillator and amplifier as the signal source; and rubidium titanyl phosphate and
      potassium titanyl arsenate nonlinear crystals. We obtained 260 fs, 30 mJ pulses
      centered at 1.550 microm, representing a gain of > 10(9) and a peak power of 100
      GW. To our knowledge, these are the highest energy and peak power pulses ever
      produced in the 1.5-2.0 microm region

PMID- 16092238
TI  - Large self-deflection of soliton beams in LiNbO3.
AB  - We report the observation of large self-deflection of 2-D bright photorefractive
      solitons in LiNbO3 crystal under a dc applied field. Beam deflection as large as
      300 microm after a 7 mm propagation distance is reported, leading to formation of
      curved 2-D waveguides. We attribute this large deflection to the low level of
      impurity acceptors present in the samples, as confirmed by numerical results from
      a time-dependent photorefractive model.

PMID- 16092239
TI  - Engineering the dispersion of tapered fibers for supercontinuum generation with a
      1064 nm pump laser.
AB  - We experimentally demonstrate dispersion tailoring of tapered fibers by immersing
      them in fluids. We obtain a 1200 nm wide supercontinuum in a train of two tapered
      fibers pumped by a low-cost diode-pumped Nd:YAG laser with a pulse width of 0.6
      ns and an output power of 40 mW, where one tapered fiber is immersed in heavy
      water. To our knowledge, this is the widest spectrum ever generated with a system
      of such simplicity.

PMID- 16092240
TI  - Engineering of multicolor spatial solitons with chirped-period quasi-phase
      matching gratings in optical parametric amplification.
AB  - We demonstrate the excitation of solitons in a parametric amplifier with enhanced
      signal content through the use of a chirped-period quasi-phase-matching grating.
      This technique affords a low soliton threshold at the input end of a parametric
      amplifier, and the subsequent transformation to a desired soliton that exists at
      nonzero wave-vector mismatch through the use of a linearly chirped quasi-phase
      matching grating. This approach has an advantage over direct excitation of
      solitons at nonzero wave-vector mismatch in uniform nonlinear materials and holds
      potential for improving the efficiency and mode quality of high-gain parametric
      amplifiers.

PMID- 16092241
TI  - Multistate polarization addressing using a single beam in an azo polymer film.
AB  - Peculiar light-matter interactions can break the rule that a single beam
      polarization can address only two states in an optical memory device. Multistate
      storage of a single beam polarization is achieved using self-induced surface
      diffraction gratings in a photoactive polymer material. The grating orientation
      follows the incident light beam's polarization direction. The permanent self
      induced surface relief grating can be read out in real time using the same laser
      beam.

PMID- 16092242
TI  - Optical circulators in two-dimensional magneto-optical photonic crystals.
AB  - We propose an optical circulator formed of a magneto-optical cavity in a 2D
      photonic crystal. With spatially engineered magnetic domain structures, the
      cavity can be designed to support a pair of counterrotating states at different
      frequencies. By coupling the cavity to three waveguides, and by proper matching
      of the frequency split of the cavity modes with the coupling strength between the
      cavity and the waveguide, ideal three-port circulators with complete isolation
      and transmission can be created. We present a guideline for domain design needed
      to maximize the modal coupling and the operational bandwidth for any given
      magneto-optical constant.

PMID- 16092243
TI  - Active optical control of the terahertz reflectivity of high-resistivity
      semiconductors.
AB  - We study theoretically and demonstrate experimentally light-controllable
      terahertz reflectivity of high-resistivity semiconductor wafers. Photocarriers
      created by interband light absorption form a thin conducting layer at the
      semiconductor surface, which allows the terahertz reflectivity of the element to
      be tuned between antireflective (R <3%) and highly reflective (R >85%) limits by
      means of the intensity and wavelength of the optical illumination.

PMID- 16092244
TI  - Polarization-invariant grating based on a photoaligned liquid crystal in an
      oppositely twisted binary configuration.
AB  - We demonstrate a polarization-invariant liquid-crystal (LC) grating in an
      oppositely twisted and mutually orthogonal configuration. The polarization
      invariant LC grating with high diffraction efficiency is fabricated using a
      single-masking process with two-step exposure of a linearly polarized ultraviolet
      light. It is found that the zeroth- and the first-order diffracted beams are
      linearly polarized and perpendicular to each other irrespective of the incident
      polarization for the phase retardation of m pi (m=integer).

PMID- 16092245
TI  - Dispersion-free pulse propagation in a negative-index material.
AB  - The possibility of controlling the spectral position of the zero group-velocity
      dispersion point of a negative-index material can be exploited by varying the
      ratio between the electric and the magnetic plasma frequency to obtain dispersion
      free propagation in spectral regions otherwise inaccessible using conventional
      positive-index materials. Our predictions are confirmed by pulse propagation
      simulations where all the orders of the complex dispersion of the material are
      taken into account.

PMID- 16092246
TI  - Coherent photon transport from spontaneous emission in one-dimensional
      waveguides.
AB  - A two-level system coupled to a one-dimensional continuum is investigated. By
      using a real-space model Hamiltonian, we show that spontaneous emission can
      coherently interfere with the continuum modes and gives interesting transport
      properties. The technique is applied to various related problems with different
      configurations, and analytical solutions are given.

PMID- 16092247
TI  - Electromagnetically induced diffraction in sodium vapor.
AB  - By using a sodium atomic vapor we have observed a honeycomb-type multiple
      diffraction pattern that was due to a grating induced optically by three
      noncollinear bichromatic excitation beams. In particular, when the two incident
      frequencies satisfy the two-photon resonance condition and the atomic density is
      high, the diffraction is enhanced by electromagnetically induced transparency,
      and strong Stokes and anti-Stokes components are generated in well-defined
      directions.

PMID- 16092248
TI  - Energy conservation of the scattering from one-dimensional random rough surfaces
      in the high-frequency limit.
AB  - Energy conservation of the scattering from one-dimensional strongly rough
      dielectric surfaces is investigated using the Kirchhoff approximation with single
      reflection and by taking the shadowing phenomenon into account, both in
      reflection and transmission. In addition, because no shadowing function in
      transmission exists in the literature, this function is presented here in detail.
      The model is reduced to the high-frequency limit (or geometric optics). The
      energy conservation criterion is investigated versus the incidence angle, the
      permittivity of the lower medium, and the surface rms slope.

PMID- 16092249
TI  - Active phase stabilization in Fourier-transform two-dimensional infrared
      spectroscopy.
AB  - A scheme for active phase stabilization and absolute positioning in Fourier
      transform two-dimensional (2D) IR spectroscopy is presented. The position
      accuracy is better than 20 nm(rms) corresponding to lambda/250 at 5 microm, which
      significantly improves the quality of Fourier-transform 2D IR spectra. Phase
      stabilization is added to a standard photon echo setup in a way that does not
      impair the flexibility of the experiment and the control over IR pulse
      parameters.

PMID- 16092250
TI  - Passive mode-locking by use of waveguide arrays.
AB  - A novel mode-locking technique is presented in which the intensity-dependent
      spatial coupling dynamics of a waveguide array is used to achieve temporal mode
      locking in a passive optical fiber laser. By use of the discrete, nearest
      neighbor spatial coupling of the waveguide array, low-intensity light can be
      transferred to the neighboring waveguides and ejected (attenuated) from the laser
      cavity. In contrast, higher-intensity light is self-focused in the waveguide and
      remains largely unaffected. Numerical studies of this pulse shaping mechanism
      (intensity discrimination) show that using current waveguide arrays and standard
      optical fiber technology produces stable and robust mode-locked soliton-like
      pulses.

PMID- 16092251
TI  - Characterization of ultrashort optical pulse properties by amplitude-modulation
      balanced heterodyne gating.
AB  - We present a general approach for the measurement of the properties of optical
      pulses by exploiting features of the optical carrier domain. We demonstrate the
      principle of a novel balanced detection scheme that avoids the difficulties
      associated with homodyne detection in the baseband used in linear optical
      sampling methods so far. The residual timing instability of the repetition rate
      synchronization between mode-locked lasers is measured with the new detection
      technique.

PMID- 16092252
TI  - Focal transformation and the Gouy phase shift of converging one-cycle surface
      acoustic waves excited by femtosecond laser pulses.
AB  - We studied the changes of the pulse shape and the phase of the spectral
      components in converging-surface acoustic wave pulses. These pulses were excited
      with a femtosecond laser by a thermoelastic mechanism. To produce converging
      acoustic pulses, the laser beam was focused with an axicon in a circle on the
      surface of an aluminum sample. During propagation through the focus, the shape of
      the pulses of the normal surface velocity changed from two to three polar. The
      absolute value of the phase of the spectral components experienced a change close
      to pi/2 rad (Gouy phase shift) after passage of the focal region. These
      observations were confirmed by analytical and numerical calculations based on the
      two-dimensional wave equation for surface acoustic waves.

PMID- 16092253
TI  - Complete characterization of periodic optical sources by use of sampled test-plus
      reference interferometry.
AB  - An interferometric technique measuring the time-dependent electric field of a
      periodic optical source that uses samples of its interference with a reference
      source of short optical pulses is presented. Compared with other test-plus
      reference techniques such as spectral interferometry and Fourier-transform
      spectroscopy, the technique is applicable when the signal under test and the
      reference signal do not originate from the same source. It is highly sensitive
      and allows the direct real-time characterization of optical sources and the
      extraction of a coherent periodic signal in an incoherent background.

PMID- 16092254
TI  - Spectral compression of femtosecond pulses in photonic crystal fibers.
AB  - We demonstrate efficient spectral compression of femtosecond pulses near the zero
      dispersion wavelength in nonlinear photonic crystal fibers (PCFs). The highest
      measured compression factor is 21, in which case the spectral brightness
      increases by a factor of 5. We numerically model the pulse propagation and find
      good agreement with the experiment. We argue that the fibers studied allow for
      spectral narrowing of more than 2 orders of magnitude. With dispersion-shifted
      PCFs, efficient spectral compression can take place across the visible and near
      infrared part of the spectrum.

PMID- 16092255
TI  - Phase-locked ultrashort pulse trains at separate and independently tunable
      wavelengths.
AB  - The generation and characterization of femtosecond pulses at three independently
      tunable visible wavelengths is reported. Selected spectral portions of a common
      continuum generated in sapphire are amplified in noncollinear optical parametric
      amplifiers. The phase relation of the pulse trains is analyzed with a nonlinear
      interferometer based on coherent anti-Stokes Raman scattering and is found to be
      locked to better than 250 mrad rms. Small spectral shifts of the pulses lead to
      interference behavior that is consistent with 1 kHz frequency combs.

PMID- 16092256
TI  - Food 21: a research program looking for measures and tools to increase food chain
      sustainability.
AB  - Food 21, an interdisciplinary research program encompassing the whole agro-food
      chain, was conducted in Sweden during 1997-2004. The challenges undertaken were
      to come up with environmental tools and solutions to existing nonsustainable
      practices along the entire food chain. This required close collaboration between
      the scientists and the food chain stakeholders. A set of goals characterizing
      sustainable food production is presented in this paper. Synthesis and systems
      analysis were the main tools used to analyze the sustainability of proposed
      changes. In this introduction we give an overview of the Food 21 concept and
      highlight some results. For example, we found that organic farming and organic
      products were not in general superior to conventional products and practices with
      respect to environmental impact and product quality. We also summarize the
      management experiences in this article, since we consider them to be rather
      unique and since they contributed to the overall success of the program.

PMID- 16092257
TI  - Perspectives and challenges in the future use of plant nutrients in tilled and
      mixed agricultural systems.
AB  - Producing an adequate quantity of healthy food without polluting the environment
      is a serious challenge for future agriculture around the world. The Food 21
      research program in Sweden has researched all aspects--economic, environmental,
      and social--of sustainable farming systems. This paper presents some of the
      research from that and other relevant international research programs that have
      focused on better nutrient-use efficiency, especially for nitrogen and
      phosphorus. It shows that a range of sustainable solutions to nutrient-use
      efficiency exists, some of which are complex but some very simple. Government
      policies, including subsidies; research and technology; and public acceptance of
      farming practices all combine to create these solutions. Participatory approaches
      to knowledge transfer are needed, in which scientists, policy makers, farmers,
      advisers, and consumers exchange information and together build sustainable
      farming systems.

PMID- 16092258
TI  - Possibilities for improving nitrogen use from organic materials in agricultural
      cropping systems.
AB  - Nitrogen release from organic nutrient sources in soil is influenced by a range
      of factors such as soil temperature and moisture, and chemical composition of the
      organic material. Chemical composition can, to a certain degree, be controlled to
      increase the synchronization of nitrogen (N) release with plant N demand, whereas
      climatic factors cannot be controlled and so must be taken into account when
      planning management measures. In this paper, we discuss different ways to affect
      N release through manipulation of the chemical composition of fresh or pretreated
      plant materials and animal manures, timing of incorporation, and intentional
      distribution during application. We conclude by giving an overview of off-farm
      options that may need to be implemented to achieve improved use of N, especially
      in agricultural systems with surplus N.

PMID- 16092259
TI  - Conditional phosphorus index as an educational tool for risk assessment and
      phosphorus management.
AB  - Phosphorus index (PI) is a risk-assessment tool that combines phosphorus (P)
      source factors and transport factors to rank the vulnerability of fields to P
      losses. Here we present the structure and concepts of conditional PI, developed
      as an educational and P-management tool adjusted for Swedish conditions. Because
      the significance of certain factors for P losses depends on their interplay with
      other factors, conditional rules are needed for a more accurate process
      description and quantification. Accounting for P losses through the soil profile,
      separate calculations for reactive and unreactive P and a changed approach to P
      loss assessment from erosion losses are some of the new features included in the
      tool presented here. The performance of the tool was tested by comparing the
      calculated PI values with measured annual P transport from seven observation
      fields included in a Swedish water quality monitoring program. This first test
      indicated that the tool could be used successfully for P loss risk assessment.

PMID- 16092260
TI  - A systems approach to assess farm-scale nutrient and trace element dynamics: a
      case study at the Ojebyn dairy farm.
AB  - A systems analysis approach was used to assess farmscale nutrient and trace
      element sustainability by combining full-scale field experiments with specific
      studies of nutrient release from mineral weathering and trace-element cycling. At
      the Ojebyn dairy farm in northern Sweden, a farm-scale case study including
      phosphorus (P), potassium (K), and zinc (Zn) was run to compare organic and
      conventional agricultural management practices. By combining different element
      balance approaches (at farmgate, barn, and field scales) and further adapting
      these to the FARMFLOW model, we were able to combine mass flows and pools within
      the subsystems and establish links between subsystems in order to make farm-scale
      predictions. It was found that internal element flows on the farm are large and
      that there are farm internal sources (Zn) and loss terms (K). The approaches
      developed and tested at the Ojebyn farm are promising and considered generally
      adaptable to any farm.

PMID- 16092261
TI  - Selection for increased production and the welfare of dairy cows: are new
      breeding goals needed?
AB  - In many European countries, milk production per cow has more than doubled in the
      last 40 years. The increase in production has been accompanied by declining
      ability to reproduce, increasing incidence of health problems, and declining
      longevity in modern dairy cows. Genetic selection for increased milk yield
      increasingly is viewed as increasing profit at the expense of reducing animal
      welfare. The economic future of the dairy industry is related directly to public
      acceptance of its breeding and production practices. It is important to the dairy
      industry that welfare problems should be addressed before there is widespread
      condemnation of breeding and management practices. A new breeding goal aimed at
      improving fitness and tolerance of metabolic stress is necessary to prevent the
      decrease in the quality of life of dairy cows and instead, perhaps, enhance it.

PMID- 16092262
TI  - Healthy and happy: animal welfare as an integral part of sustainable agriculture.
AB  - Good animal welfare is necessary if an agricultural system is to be sustainable.
      Although we have been concerned about the welfare of our animals since we first
      domesticated them and became dependent on their health and reproduction, this
      article focuses mainly on the development of the animal welfare debate since the
      1960s. It presents animal welfare as a science that arose from society's concern
      about the way animals are kept. These moral and ethical concerns lead to it
      having a value framework that must also be taken into consideration. Different
      definitions of animal welfare, as well as examples of research, are presented and
      discussed in the light of developments in this area. For example, in recent years
      there has been an increased interest among consumers for animal-friendly
      products, as there has been for environment friendly products, and this has
      stimulated the move from experimental studies of animal welfare to its
      application in practice and to monitoring animal welfare on farms. Traditionally
      such measurements have been resource based, e.g. specifying the minimum amount of
      feeding space or the maximum stocking density, but now the trend is toward animal
      based measures, such as the numberof lame animals, body condition, etc.

PMID- 16092263
TI  - Genomics meets ethology: a new route to understanding domestication, behavior,
      and sustainability in animal breeding.
AB  - Animal behavior is a central part of animal welfare, a keystone in sustainable
      animal breeding. During domestication, animals have adapted with respect to
      behavior and an array of other traits. We compared the behavior of junglefowl and
      White Leghorn layers, selected for egg production (and indirectly for growth).
      Jungle-fowl had a more active behavior in social, exploratory, anti-predatory,
      and feeding tests. A genome scan for Quantitative Trait Loci (QTLs) in a
      junglefowl x White Leghorn intercross revealed several significant or suggestive
      QTLs for different traits. Some production QTLs coincided with QTLs for behavior,
      suggesting that pleiotropic effects may be important for the development of
      domestication phenotypes. One gene has been located, which has a strong effect on
      the risk of being a victim of feather pecking, a detrimental behavior disorder.
      Modern genomics paired with analysis of behavior may help in designing more
      sustainable and robust breeding in the future.

PMID- 16092264
TI  - Integration of natural behavior in housing systems.
AB  - This paper deals with how the natural behavior of animals kept for production can
      be integrated when planning new housing systems or making changes to existing
      housing systems. Natural behavior can be defined as the repertoire of different
      behaviors animals show when kept in environments where they can carry out
      behaviors created in the evolutionary process. Motivation and innate behaviors
      are important aspects of natural behavior, and hindering them may lead to
      abnormal behavior and stress. One should first get a basic knowledge about the
      species-specific behavior in the wild or a seminatural environment. Thereafter,
      key stimuli and key features for normal behavior should be worked out, where
      after a reduction in space, development of a pen, scientific testing,
      modification, and finally testing the function in a larger scale should be
      carried out. Examples of housing of calves during the milk period and housing of
      sows around farrowing are given.

PMID- 16092265
TI  - Phenolic compounds in oat grains (Avena sativa L.) grown in conventional and
      organic systems.
AB  - The concentrations of avenanthramides (AVAs), hydroxycinnamic acids (HCAs), a
      sucrose-linked truxinic acid (TASE), and certain agronomic parameters were
      analyzed in organically and conventionally grown oats. Three cultivars of oats
      (i.e. Freja, Sang, and Matilda) were grown according to standards for both
      conventional and organic farming in Sweden, from 1998 to 2000. Two levels of
      nitrogen (N) and three replicates were included. Overall, there were significant
      differences between years, cultivars, and N rate for AVA concentration in the
      grains, but there were no differences in concentration as a consequence of the
      conventional or organic cropping system used. The AVA content was higher in the
      samples grown in 2000, particularly in the cultivar Matilda, and was negatively
      affected by higher N rates. The HCAs showed cultivar and year differences, but
      were not influenced by N rates or the cropping system. The HCA content was
      highest in Matilda, and was significantly lower in samples grown in 1999. The
      concentration of TASE differed only between years, and was about 100% higher in
      samples from 1999, compared with samples from 1998 and 2000. The AVA and HCA
      concentrations were negatively correlated to the yield and specific weight of the
      grains and positively correlated to the protein content. Conversely, the
      concentration of TASE was positively correlated to the yield. The specific
      parameters responsible for the variation in the phenolic compounds are not known,
      but it seems that factors affecting the yield and/or the specific weight also
      affect the concentrations of AVAs, HCAs, and TASE in oat grains.

PMID- 16092266
TI  - The influence of production systems on meat quality, with emphasis on pork.
AB  - Technological, nutritional, and sensory meat quality may be influenced by
      multiple interacting factors before and after slaughter. Reviewing the
      literature, it can be seen that alterations aimed at creating more sustainable
      production systems for pig meat generally have either no effect or a lowering
      effect on the ultimate pH value of the meat. Some studies indicate reduced water
      holding capacity in sustainably produced pork. Outdoor production may be expected
      to increase further the shear force of the meat compared to conventional systems.
      The color may be affected in different ways, leading to either darker, more
      pigmented meat or paler, structurally effected meat. The more unsaturated profile
      of the lipids in meat produced in a system that includes feeds containing
      polyunsaturated fatty acids is favorable with respect to the nutritional quality
      of the meat. To conclude, the combinatory effects of, for example, feeding,
      production systems, genotype, sex, and preslaughter treatments, have to be
      addressed.

PMID- 16092267
TI  - Cadmium in food production systems: a health risk for sensitive population
      groups.
AB  - This paper gives an overview of the cadmium (Cd) situation in agricultural
      systems and human exposure in Sweden. Cadmium levels in agricultural soils (the
      plow layer) increase by 0.03% to 0.05% per year. Feed can give substantial
      contributions of Cd to local agricultural systems. Effects on human kidney
      function are indicated by some measurements already at today's exposure levels.
      If food products reach the maximum permissible levels given by the European
      Union, 10% to 25% of the Swedish population will be exposed to Cd levels above
      the provisional tolerable weekly intake (PTWI 7 microg Cd kg(-1) body weight).
      Sensitive groups in the population are individuals with low iron status (mainly
      women) and kidney disorders. Recent studies indicate that Cd plays a role in
      osteoporosis and that further research is needed to clarify if Cd is neurotoxic
      in early developmental stages. Firm actions have to be taken in order to stop a
      further increase of Cd in agricultural soils. Suggestions for prevention and
      measures are given in this paper.

PMID- 16092268
TI  - Determinants of consumer behavior related to organic foods.
AB  - There have been many studies of what influences consumers in their decisions to
      purchase or consume organic foods, mainly concerned with fresh organic foods.
      These show a discrepancy between attitudes and behavior with people being
      positive about organic foods but often not purchasing them. This discrepancy
      seems to be explained by the fact that consumers do not consider "organically
      produced" to be an important purchase criterion, that organic foods are not
      perceived to surpass conventional foods regarding taste and shelf life (two
      qualities rated to be of great importance), and because of the perceived premium
      prices of organic foods. In two Swedish studies, health benefits were
      demonstrated to be more strongly related to attitudes and behavior toward organic
      foods than were perceived environmental benefits. A new European Union (EU)
      project will investigate the influences on both fresh and processed organic foods
      and investigate the role of moral, ethical, and affective influences on choice
      across eight EU countries.

PMID- 16092269
TI  - Habitual and value-guided purchase behavior.
AB  - Society increasingly requests that individuals adopt environmentally benign
      behavior. Information campaigns purported to change people's attitudes are often
      regarded as prerequisites to installing such changes. While such information may
      be a necessary step, it is not sufficient by itself. We argue that many everyday
      behaviors with environmental consequences are habitual, and that little attention
      is given to information directed toward changing these habitual behaviors. In
      other instances, behavior is guided by values in a more reflective process.
      However, other information besides environmental consequences may draw a person's
      attention and affect behavioral choice. Using surveys and experimental studies
      targeting consumer behavior, we studied under what conditions different kinds of
      information is likely to influence people with varying levels of environmental
      concern. Based on results from these studies, implications for behavioral change
      are discussed.

PMID- 16092270
TI  - Consumer preferences for food product quality attributes from Swedish
      agriculture.
AB  - This paper employs a choice experiment to obtain consumer preferences and
      willingness to pay for food product quality attributes currently not available in
      Sweden. Data were obtained from a large mail survey and estimated with a random
      parameter logit model. We found evidence for intraproduct differences in consumer
      preferences for identical attributes, as well as interproduct discrepancies in
      ranking of attributes. Furthermore, we found evidence of a market failure
      relating to the potential use of genetically modified animal fodder. Finally, we
      found support for the idea that a cheap-talk script can alleviate problems of
      external validity of choice experiments. Our results are useful in forming
      product differentiation strategies within the food industry, as well as for the
      formation of food policy.

PMID- 16092272
TI  - Social sustainability and collaborative learning.
AB  - The social dimension is central to sustainable development of agri-food systems.
      If farmers are not satisfied with their situation or motivated to continue
      farming, many of today's environmental goals will be impossible to achieve.
      Between 1997 and 2003, several case studies were carried out on social
      sustainability, the importance of recognition in the farming system, and the
      potential role of increased collaboration between actors. The main hypothesis was
      that improved recognition is a basis for sustainable social conditions. Our
      findings show that many farmers today perceive an impoverished social situation.
      They believe they lack control over decisions, which hinders their ability to
      continue farming. Public images and political decisions show a lack of respect
      for farmers' skills and knowledge. However, increased collaboration among actors
      is believed to be one important way forward, creating stronger relationships and
      networks, as well as a stronger identity for farmers. Our findings emphasize the
      need for authorities and other organizations to support farmers and to facilitate
      collaborative learning and decision-making processes for socioecological
      sustainability.

PMID- 16092271
TI  - Home transport and wastage: environmentally relevant household activities in the
      life cycle of food.
AB  - In environmental systems analysis of food production systems, the consumer phase
      (home transport, cooking, storing, and wastage) is an important contributor to
      the total life-cycle environmental impact. However, households are the least
      investigated part of the food chain. Information gathering about households
      involves difficulties; the number of households is large, and food-related
      activities are embedded in other household activities. In cooperation between
      researchers from environmental systems analysis and consumer research, Swedish
      households were surveyed by questionnaire, diary, and interviews. Data on home
      transport of food and wastage were collected. The average weekly driving distance
      was 28 to 63 km per household, depending on how trips made in conjunction with
      other errands are allocated. The wastage of prepared food ranged between 0 and
      34% for different food categories, and wastage from storing between 0 and 164%
      (more food was discarded, e.g. by cleaning out a cupboard, than consumed). In
      both cases dairy products scored highest.

PMID- 16092273
TI  - Farm cooperation to improve sustainability.
AB  - In this paper, it is demonstrated that partnership arrangements between farmers
      might be a way to secure the economic viability of their farms as well as to
      increase profitability. The article discusses empirical analyses of three
      different forms of collaboration, with an emphasis on the environmental
      improvements associated with collaboration. Collaboration between a dairy farm
      and a crop farm is analyzed in the first case. The results show that potential
      gains from improved diversification and crop rotation are substantial, and even
      larger when the collaboration also involves machinery. The second analysis
      considers external integration between farrowing and finishing-pig operations.
      Gains from collaboration originate from biological and technical factors, such as
      improved growth rate of the pigs and better utilization of buildings. Finally, an
      evaluation of a group of collaborating crop farmers is performed. In this case,
      the benefits that arise are mainly due to reduced machinery costs and/or gains
      due to other factors, such as improved crop rotation and managerial/marketing
      strategies.

PMID- 16092274
TI  - SALSA: a simulation tool to assess ecological sustainability of agricultural
      production.
AB  - In order to assess the ecological sustainability of agricultural production
      systems, there is a need for effective tools. We describe an environmental
      systems analysis tool called SALSA (Systems Ana/ysis for Sustainable
      Agriculture). It consists of substance/material flow models in which the
      simulation results are interpreted with life-cycle assessment methodology. The
      application of SALSA is demonstrated in a case study in which three different
      ways of producing pigs are compared with respect to energy input and the
      environmental impacts of global warming, eutrophication, and acidification. The
      scenario that combined a low-protein diet without soy meal with an improved
      manure-management technique with low nitrogen losses was the best for all impact
      categories studied. The strength of the SALSA models was their capacity to
      capture consequences of management options that had an influence on several
      processes on a farm, which enabled the type of complex studies we describe.

PMID- 16092275
TI  - Environmental and economic impacts of decision-making at an arable farm: an
      integrative modeling approach.
AB  - This study examines the dependency between physical and anthropogenic systems in
      arable farming. The dynamic simulation model, which has its methodological
      origins in the modeling traditions of environmental systems analysis and
      microsimulation, reproduces the mutual links between the physical flows (e.g.
      energy, materials, emissions, and products), the farmer as a decision-making
      agent, and structural conditions influencing the farm. In running the model, the
      intention is to answer the question: What are the impacts on profitability and
      the environment (i.e. greenhouse gas effects, eutrophication, acidification, and
      energy use) of variations in prices, subsidies, the farmer's environmental
      values, and the farmer's skill in making production allocation choices? The
      results of the model simulations indicate, for example, that in terms of economic
      performance, a farmer can choose between two relatively sustainable strategies-
      either to specialize in organic production (thereby benefiting from higher
      subsidies and output prices), or to focus on conventional cultivation and use of
      pesticides and fertilizers (thereby benefiting from large yields). Regarding
      environmental impacts, there was no clear-cut divide between organic and
      conventional farming due to difficulties in allocating the use of manure. This
      finding is essentially related to the choice of system boundary, which is
      thoroughly discussed in the paper.

PMID- 16092276
TI  - Sustainable development of food production: a case study on scenarios for pig
      production.
AB  - To study future, sustainable production systems, a step-wise method was used to
      create three future scenarios for pig production based on different
      sustainability goals. The first scenario focused on animal welfare and the
      natural behavior of the animals. The second targeted low impacts on the
      environment and the efficient use of natural resources. The third scenario aimed
      at product quality and safety. Each scenario fulfilled different aspects of
      sustainability, but there were goal conflicts because no scenario fulfilled all
      sustainability goals. The scenarios were then parameterized. The environmental
      impact was calculated using the life-cycle assessment (LCA) methodology, and the
      economic cost was calculated from the same data set. The cost per kilo of pork
      was highest for the animal welfare scenario and similar for the other two
      scenarios. The environmental scenario had the lowest environmental impact, and
      the product-quality scenario the highest. The results are discussed based on
      different future priorities.

PMID- 16092277
TI  - Environmental assessment of plant protection strategies using scenarios for pig
      feed production.
AB  - Two scenarios for future pig meat production were constructed. The first was a
      "business as usual" scenario, where the pig feed was based on domestic grain and
      imported soy-meal, and no efforts were made to reduce pesticide use. The second
      scenario had a strong environmental focus, and both peas and rapeseed were grown
      at pig-farm level to produce grain and protein feed. Preventive measures, such as
      a more diverse crop rotation and mechanical weed control, were combined to reduce
      pesticide use. The two scenarios were environmentally assessed by Life Cycle
      Assessment (LCA) and a pesticide risk indicator model (PRI-Farm). The results
      showed environmentally sound possibilities to reduce pesticide dependency and
      risks by using altered plant protection strategies in pig-feed production.
      Organizing on-farm feed production so that protein feed crops are integrated with
      grain crops contributes to a more diverse crop rotation.

PMID- 16092278
TI  - Industrial processing versus home cooking: an environmental comparison between
      three ways to prepare a meal.
AB  - Today there is a strong trend in Sweden for industrially processed meals to
      replace homemade meals. In the public debate this is often claimed to increase
      the environmental impact from foods. In the study presented in this article, we
      used life-cycle assessment to quantify the environmental impact of three meals:
      homemade, semiprepared, and ready-to-eat. The differences in environmental impact
      between the meals were small; the ready-to-eat meal used the most energy, whereas
      the homemade meal had higher emissions causing eutrophication and global warming.
      The dominating contributor to the environmental impact was agriculture,
      accounting for 30%, of the impact related to energy and 95% of that related to
      eutrophication. Industry, packaging, and consumer home transport and food
      preparation also contributed significantly. Important factors were raw material
      use, energy efficiency in industry and households, packaging, and residue
      treatment. To decrease the overall environmental impact of food consumption,
      improvements in agriculture are very important, together with raw-material use
      within industry and households.

PMID- 16092279
TI  - Government moves to enshrine infection control in law.

PMID- 16092280
TI  - A key role in smoking cessation.

PMID- 16092281
TI  - Safety in numbers.

PMID- 16092282
TI  - Patients' right to decide whether to be resuscitated.
AB  - While the issue of do-not-resuscitate orders is often discussed in nursing
      journals, there appears to be little consideration given to the other side of the
      issue--are some patients in danger of being resuscitated when they would prefer
      to be left alone? This article looks at whether all patients should be asked what
      their preferences are regarding resuscitation.

PMID- 16092283
TI  - The heart: Part one--the anatomy.

PMID- 16092284
TI  - Erythromycin.

PMID- 16092285
TI  - Empowering families to care for people with schizophrenia.
AB  - This article examines how community psychiatric nurses (CPNs) can assist the
      relatives and carers of patients with schizophrenia to increase their knowledge
      of the condition as well as widening their coping abilities. The practicalities
      of how CPNs can help families to gain the necessary knowledge and skills are
      considered, as well as factors that contribute to deterioration in the health of
      the family and how CPNs can help to prevent this.

PMID- 16092286
TI  - Guiding principles for patient-centred cancer services.
AB  - Cancer can affect anyone, anywhere, but not all those diagnosed have ready access
      to appropriate services. Macmillan Cancer Relief set out to determine what
      hindrances make it difficult to receive support while experiencing cancer.
      Services that overcame barriers were analysed, and the defining elements of these
      were built into guiding principles for organising cancer services.

PMID- 16092287
TI  - Practice placements for students: a literature review.
AB  - The function of practice placements is to give nursing students the chance to put
      theory into practice and become critical thinkers. This can be done using a range
      of teaching strategies such as demonstration, case conferences, questioning and
      role modelling (Quinn, 2000). Factors that enhance or inhibit learning must be
      recognised by both practitioners and educators.

PMID- 16092288
TI  - Make your workplace better by design.

PMID- 16092289
TI  - Nurses take a lead in mental health.

PMID- 16092290
TI  - A report into the eating habits of schoolchildren.

PMID- 16092291
TI  - Understanding the impacts of the Medicare Modernization Act: concerns of
      congressional staff.
AB  - Sweeping changes to the Medicare program embodied in the Medicare Prescription
      Drug, Improvement, and Modernization Act of 2003 (MMA), including a new
      prescription drug benefit, changes in payment policies, and reform of the
      Medicare managed-care program, have major implications for rural health care. The
      most efficient mechanism for research to affect policy is to provide policy
      makers with information on issues about which they have voiced concern. The Rural
      Policy Research Institute's Health Panel conducted 2 focus groups with 16
      congressional staff in September 2004 to identify a set of researchable questions
      concerning the impact of the MMA on rural health care. This paper presents
      research questions in the following areas that staff identified as having the
      highest priority: access to health plans and pharmacy services, beneficiary
      outreach and enrollment, technology capacity, provider payment policy, and
      demonstration projects.

PMID- 16092292
TI  - Primary and specialty medical care among ethnically diverse, older rural adults
      with type 2 diabetes: the ELDER Diabetes Study.
AB  - PURPOSE: Residents in rural communities in the United States, especially ethnic
      minority group members, have limited access to primary and specialty health care
      that is critical for diabetes management. This study examines primary and
      specialty medical care utilization among a rural, ethnically diverse, older adult
      population with diabetes. METHODS: Data were drawn from a cross-sectional face-to
      face survey of randomly selected African American (n=220), Native American
      (n=181), and white (n=297) Medicare beneficiaries > or =65 years old with
      diabetes in 2 rural counties in central North Carolina. Participants were asked
      about utilization of a primary care doctor and of specialists (nutritionist,
      diabetes specialist, eye doctor, bladder specialist, kidney specialist, heart
      specialist, foot specialist) in the past year. FINDINGS: Virtually all
      respondents (99.0%) reported having a primary care doctor and seeing that doctor
      in the past year. About 42% reported seeing a doctor for diabetes-related care.
      On average, participants reported seeing 2 specialists in the past year, and 54%
      reported i seeing >1 specialist. Few reported seeing a diabetes specialist
      (5.7%), nutritionist (10.9%), or kidney specialist (17.5%). African Americans
      were more likely than others to report seeing a foot specialist (P < .01), while
      men were more likely than women to have seen bladder specialist (P = .02), kidney
      specialist (P = .001), and heart specialist (P = .004), after adjusting for
      potential confounders. Predictors of the number of specialists seen include
      gender, education, poverty status, diabetes medication use, and self-rated
      health. CONCLUSIONS: These data indicate low utilization of specialty diabetes
      care providers across ethnic groups and reflect the importance of primary care
      providers in diabetes care in rural areas.

PMID- 16092293
TI  - Perceived barriers to health care access among rural older adults: a qualitative
      study.
AB  - CONTEXT: Many rural elders experience limited access to health care. The majority
      of what we know about this issue has been based upon quantitative studies, yet
      qualitative studies might offer additional insight into individual perceptions of
      health care access. PURPOSE: To examine what barriers rural elders report when
      accessing needed health care, including how they cope with the high cost of
      prescription medication. METHODS: During Spring 2001, thirteen 90-minute focus
      groups were conducted in 6 rural West Virginia communities. A total of 101
      participants, aged 60 years and older, were asked several culminating questions
      about their perceptions of health care access. FINDINGS: Five categories of
      barriers to health care emerged from the discussions: transportation
      difficulties, limited health care supply, lack of quality health care, social
      isolation, and financial constraints. In addition, 6 diverse coping strategies
      for dealing with the cost of prescription medication were discussed. They
      included: reducing dosage or doing without, limiting other expenses, relying on
      family assistance, supplementing with alternative medicine, shopping around for
      cheapest prices, and using the Veteran's Administration. CONCLUSIONS: Overall,
      rural older adults encounter various barriers to accessing needed health care.
      Qualitative methodology allows rural elders to have a voice to expound on their
      experiences. Research can contribute valuable information to shape policy by
      providing a forum where older adults can express their concerns about the current
      health care delivery system.

PMID- 16092294
TI  - Changes in age-adjusted mortality rates and disparities for rural physician
      shortage areas staffed by the National Health Service Corps: 1984-1998.
AB  - OBJECTIVE: This study assesses whether the National Health Service Corps's
      legislated goals to see health improve and health disparities lessen are being
      met in rural health professional shortage areas for a key population health
      indicator: age-adjusted mortality. METHODS: In a descriptive study using a pre
      post design with comparison groups, the authors calculated age-adjusted mortality
      rates at baseline (1981-1983) and follow-up (1996-1998) for the populations of
      448 rural whole-county health professional shortage areas arrayed into 3 groups
      based on the number of study years they were staffed by National Health Service
      Corps physicians, physician assistants, and nurse practitioners (terms of 1 to 7,
      8 to 11, and 12 to 15 years). The authors compared changes over time in age
      adjusted mortality rates in the 3 county groups that had National Health Service
      Corps staffing with rate changes in 172 whole-county rural health professional
      shortage areas and 772 non-health professional shortage area rural counties that
      had no National Health Service Corps. RESULTS: At baseline age-adjusted mortality
      was higher in all 4 health professional shortage area county groups than in the
      non-health professional shortage area county group. Age-adjusted mortality rates
      improved with time in all groups, including health professional shortage area
      counties both with and without National Health Service Corps support, and non
      health professional shortage area counties. Essentially, baseline differences in
      age-adjusted mortality rates between health professional shortage areas and non
      health professional shortage area counties did not diminish with time, whether or
      not there was National Health Service Corps support. CONCLUSIONS: From the early
      1980s through the mid-1990s, the National Health Service Corps's goal to see
      health improve in rural health professional shortage areas was met, but its goal
      to diminish geographical health disparities was not. Because age-adjusted
      mortality rates improved in all county groups, the authors conclude that
      improvement was likely due to a variety of factors, including decreasing poverty
      and unemployment rates and increasing primary care physician-to-population
      ratios, to which the National Health Service Corps may have contributed.

PMID- 16092295
TI  - Physicians for rural America: the role of institutional commitment within
      academic medical centers.
AB  - CONTEXT: Prior study suggests that contextual characteristics of medical schools
      (e.g., state demographics, public vs private, NIH research effort) predict output
      of rural physicians without also considering the effects of the medical schools'
      own policies and programs. PURPOSE: This study examines medical school commitment
      to rural policies and programs and its relationship to contextual characteristics
      and rural physician output. METHODS: A survey of 122 U.S. allopathic medical
      schools provided data to construct a 32-item Rural Commitment Index for each
      medical school. Data for other characteristics were linked from published
      sources. Correlations, t tests, and multiple regression analysis were used to
      study the association between variables and percentage of medical school
      graduates (1988-1996) who were in rural primary care practice in 2000. FINDINGS:
      Among 90 medical schools (response rate, 73.8%), the Rural Commitment Index
      correlated with the percentage of the state population that is rural and whether
      the school is public or private, and it joined percentage state population rural,
      public vs private, and National Institutes of Health support in correlating with
      percentage of graduates in rural primary care. In a regression model that
      explained 48.4% of variation in the percentage of graduates in rural primary
      care, the Rural Commitment Index explained most variation, followed by percentage
      state population rural, public vs private, National Institutes of Health support,
      and the interaction between the Rural Commitment Index and public vs private.
      CONCLUSIONS: The findings support the proposition that observable institutional
      commitment affects rural physician output and provide justification for a
      definitive study to verify that a change in medical school commitment to rural
      medicine produces a change in rural physician output.

PMID- 16092296
TI  - High school census tract information predicts practice in rural and minority
      communities.
AB  - PURPOSE: Identify census-derived characteristics of residency graduates' high
      school communities that predict practice in rural, medically underserved, and
      high minority-population settings. METHODS: Cohort study of 214 graduates of the
      University of California, San Francisco-Fresno Family Practice Residency Program
      (UCSF-Fresno) from its establishment in 1970 through 2000. Rural-urban commuting
      area code; education, racial, and ethnic distribution; median income; population;
      and federal designation as a medically underserved area were collected for census
      tracts of each graduate's (1) high school address and (2) practice location.
      FINDINGS: Twenty-one percent of graduates practice in rural areas, 28% practice
      in areas with high proportions of minority population (high minority areas), and
      35% practice in federally designated medically underserved areas. Graduation from
      high school in a rural census tract was associated with rural practice (P < .01),
      Of those practicing in a rural site, 32% graduated from a rural high school, as
      compared with 11% of nonrural practitioners. Graduation from high school in a
      census tract with a higher proportion of minorities was associated with practice
      in a proportionally high minority community (P = .01). For those practicing in a
      high-minority setting, the median minority percentage of the high school census
      tract was 31%, compared with 16% for people not practicing in a high minority
      area. No characteristics of the high school census tract were predictive of
      practice in a medically underserved area. CONCLUSION: Census data from the
      residency graduate's high school predicted rural practice and practice in a
      proportionally high minority community, but not in a federally designated
      medically underserved area.

PMID- 16092297
TI  - Where a cancer patient dies: the effect of rural residency.
AB  - CONTEXT: Surveys indicate 50% to 80% of cancer patients would choose to die at
      home if possible, although far fewer actually do. In Nova Scotia (NS), cancer
      deaths occurring out-of-hospital increased from 19.8% in 1992 to 30.2% in 1997.
      The impact of rural residency on this trend has not been studied. PURPOSE: To
      determine the association between dying of cancer in a rural locale and the
      likelihood of it being an out-of-hospital death. METHODS: Secondary analysis of
      linked population-based administrative health data files. Subjects were all Nova
      Scotians who died of cancer from 1992 to 1997. Measures included location of
      death, dichotomized as a hospital death or an out-of-hospital death; and urban
      rural residency, using an enumeration area urban-rural indicator created from
      postal code information adjusted for individual characteristics. RESULTS: Of the
      13,652 total cancer deaths, 6171 occurred in rural NS, of whichl 1471 (23.8%)
      died out-of-hospital. Out-of-hospital deaths in rural NS increased from 16.2% in
      1992 to just over 27% in 1997. Compared with urban cancer patients, the adjusted
      odds of an out-of-hospital death in rural NS was lower (adjusted odds ratio,
      0.87; 95% confidence interval, 0.79-0.95). CONCLUSIONS: There was an increasing
      trend during the 1990s for cancer patients to die out-of-hospital. Compared with
      their urban counterparts, patients in rural areas were less likely to do so.
      Those with cancer living in the rural setting who wish to die at home may face
      unique challenges.

PMID- 16092298
TI  - Urban, rural, and regional variations in physical activity.
AB  - PURPOSE: There is some speculation about geographic differences in physical
      activity (PA) levels. We examined the prevalence of physical inactivity (PIA) and
      whether U.S. citizens met the recommended levels of PA across the United States.
      In addition, the association between PIA/PA and degree of urbanization in the 4
      main U.S. regions (Northeast, Midwest, South, and West) was determined. METHODS:
      Participants were 178,161 respondents to the 2000 Behavioral Risk Factor
      Surveillance System (BRFSS). Data from 49 states and the District of Columbia
      were included (excluding Alaska). States were categorized by urban status
      according to the U.S. Department of Agriculture. Physical activity variables were
      those commonly used in national surveillance systems (PIA = no leisure-time PA;
      and PA = meeting a PA recommendation). RESULTS: Nationally, PA levels were higher
      in urban areas than in rural areas; correspondingly, PIA levels were higher in
      rural areas than in urban areas. Regionally, the urban-rural differences were
      most striking in the South and were, in fact, often absent in other regions.
      Demographic factors appeared to modify the association. CONCLUSION: The
      association between PA and degree of urbanization is evident and robust in the
      South but cannot be generalized to all regions of the United States. For the most
      part, the Midwest and the Northeast do not experience any relationship between PA
      and urbanization, whereas, in the West, the trend appears to be opposite of that
      observed in the South.

PMID- 16092299
TI  - HIV in predominantly rural areas of the United States.
AB  - BACKGROUND: The burden of HIV/AIDS has not been described for certain rural areas
      of the United States (Appalachia, the Southeast Region, the Mississippi Delta,
      and the US-Mexico Border), where barriers to receiving HIV services include rural
      residence, poverty, unemployment, and lack of education. METHODS: We used data
      from Centers for Disease Control and Prevention (CDC) HIV/AIDS Reporting System
      to determine the rates of HIV (data from 29 states) and AIDS diagnoses (data from
      50 states and the District of Columbia) in 2000 for the 4 regions by demographic
      and residential (rural and economic indicators of county of residence)
      characteristics. RESULTS: The rate of HIV diagnoses in 2000 was lower in rural
      areas (7.3 per 100,000) than in suburban (8.6 per 100,000) or urban areas (22.7
      per 100,000). The highest race-adjusted rate was observed for the US-Mexico
      Border (21.1 per 100,000), followed by the Mississippi Delta (17.3 per 100,000),
      Southeast Region (14.7 per 100,000), and Appalachia (10.4 per 100,000).
      Heterosexually acquired HIV was more common in the Southeast Region and the
      Mississippi Delta than elsewhere. The Mississippi Delta had the highest
      proportion of HIV diagnoses among young people aged 13-24 years (18.4%). More
      than three quarters of people diagnosed with HIV in the Mississippi Delta and the
      Southeast Region were black, and diagnosis rates were higher among blacks and
      Hispanics than whites in all regions. The distribution of demographic and
      residential characteristics among people with AIDS was similar to that of all
      people with a diagnosis of HIV. CONCLUSION: Strategies are needed to reach the
      populations of these areas to reduce transmission of HIV.

PMID- 16092300
TI  - Dental decay in southern Illinois migrant and seasonal farmworkers: an analysis
      of clinical data.
AB  - CONTEXT: Migrant and seasonal farmworkers are a population at risk for oral
      health problems. Data on the oral health conditions of migrant and seasonal
      farmworkers' permanent teeth are particularly lacking. PURPOSE: To document the
      relative rates of treated and untreated dental decay in a sample of southern
      Illinois migrant and seasonal farmworkers who had sought care at a farmworker
      health center dental clinic. METHODS: Existing migrant health dental clinic
      records from 1995-2002 were reviewed. Final sample size was 650. Data for
      decayed, missing, and filled tooth surfaces were recorded using both anatomical
      recording and treatment notes. FINDINGS: Sixty-nine percent of migrant
      farmworkers had at least 1 decayed (untreated) tooth surface, and more than half
      had 3 or more decayed surfaces. CONCLUSIONS: Results indicate that untreated
      dental decay is significant among migrant and seasonal farmworkers who seek care
      at this dental clinic. Recommendations include addressing barriers to care,
      improved monitoring of dental health conditions, and further research to better
      document the treatment needs of this population.

PMID- 16092301
TI  - Teenage pregnancy in the Texas Panhandle.
AB  - PURPOSE: This study compares rural and small-city teenage and adult pregnancies,
      with respect to complication rates and pregnancy outcomes. METHODS: Chart review
      of Medicaid patients (513 teenage [under 20 years] and 174 adult controls [ages
      25-34]) delivered (excluding multiple gestation) in Amarillo, Texas, from January
      1999 to April 2001. Demographic data collected included maternal race, gravidity,
      parity, smoking status, drug usage, presence of antenatally diagnosed sexually
      transmitted disease(s), county type (rural vs small city) and number of prenatal
      visits. Outcomes included mode of delivery, primary cesarean section rates,
      preterm birth (<34 or <37 weeks), birth weight, birth weight <2500 g,
      preeclampsia, total maternal weight gain, hemoglobin changes after delivery,
      Apgar scores, and neonatal intensive care unit admissions. Statistical
      comparisons between groups were made for a number of factors and outcomes (P <
      .05). RESULTS: Teenagers did not have a significantly higher frequency of either
      illicit drug or tobacco usage, but teenagers <17 years had a greater incidence of
      sexually transmitted diseases (19.8% vs 10.4%, P < .008) and preeclampsia (7.1%
      vs 2.3%, P < .025, odds ratio 3.2 [1.1 to 9.9]) when compared with adults. The
      total weight gain was highest for teens < or =17 years (36.4 pounds vs adults:
      28.2, P < .001). The primary cesarean section rate was higher in adults (all
      teens 18.5% vs adults 38.6%, P < 001). County rurality had no impact on any of
      the observed findings or variables tested. CONCLUSIONS: Young teenagers have a
      higher incidence of sexually transmitted diseases and preeclampsia and also gain
      significantly more weight with pregnancy than young adults. However, the
      pregnancy outcomes were no different for rural vs small city teens.

PMID- 16092302
TI  - Information technologies in Florida's rural hospitals: does system affiliation
      matter?
AB  - CONTEXT: The recent explosive growth of information technology in hospitals
      promises to improve hospital and patient outcomes. Financial barriers may cause
      rural hospitals to lag in adoption of information technology, however, formal
      studies that examine rural hospital adoption of information technology are
      lacking. PURPOSE: To determine the extent to which rural Florida hospitals
      utilize clinical and other information technology applications, to identify
      related information technology issues and barriers, and to explore differences
      between stand-alone and system-affiliated hospitals. METHODS: Chief information
      officers in rural Florida hospitals were surveyed from June 2003-October 2003. A
      comprehensive set of questions assessed hospital demographics, information
      technology priorities and barriers, clinical and other information technology
      systems, and staffing needs. FINDINGS: In rural Florida, current information
      technology priorities included upgrading security on information technology
      systems to meet Health Insurance Portability and Accountability Act requirements
      (53.6%), implementing technology to reduce medical errors and to promote patient
      safety (50.0%), and implementing wireless systems (46.4%). With respect to
      current information technology adoption, system-affiliated rural hospitals were
      statistically more likely than their stand-alone counterparts to have laboratory
      information systems (93% vs 39%), pharmacy (87% vs 46%), pharmacy dispensing (53%
      vs 8%), chart deficiency (60% vs 15%), and order communication results (60% vs
      23%). Financial barriers to successful information technology implementation were
      noted by 69% of stand-alone and 20% of system-affiliated rural hospitals.
      CONCLUSIONS: Although top information technology priorities are similar for all
      rural hospitals examined, differences exist between system-affiliated and stand
      alone hospitals in adoption of specific information technology applications and
      with barriers to information technology adoption.

PMID- 16092303
TI  - Impact of institution of a stroke program upon referral bias at a rural academic
      medical center.
AB  - CONTEXT: Referral bias reflecting the preferential hospital transfer of patients
      with intracerebral hemorrhage (ICH) has been demonstrated as the major
      contributing factor for an observed high nonrisk-adjusted in-hospital crude acute
      stroke mortality rate at a rural academic medical center. PURPOSE: This study was
      done to assess the impact of a clinical acute stroke program upon referral bias
      in August 2000. METHODS: A chart review of acute stroke (DRG 14) discharges
      during 2001 from a rural academic medical center was compared with the same data
      from 1999. RESULTS: The odds ratio of ICH in hospital-transfer patients compared
      with nonhospital-transfer patients decreased from 11.7 in 1999 to 3.2 in 2001 (P
      < .035). CONCLUSIONS: This study demonstrated the rapid magnitude and
      significance that clinical programs can have upon referral bias. Changes in
      referral bias may be more rapid at rural academic medical centers because of the
      relative lack of health care delivery competition.

PMID- 16092304
TI  - Factors associated with incidence of "inappropriate" ambulance transport in rural
      areas in cases of moderate to severe head injury in children.
AB  - CONTEXT: Ambulance transport of pediatric trauma patients to designated trauma
      centers in cases of moderate and severe injury is not always performed, which has
      been shown to result in poor treatment outcomes. Determination of factors
      involved in inappropriate patient transport, especially in rural areas, remains
      an important avenue of research. PURPOSE: To identify factors involved in
      ambulance transport of pediatric patients sustaining moderate-to-severe head
      injury to nondesignated trauma centers in rural North Dakota. METHOD: Emergency
      medical service ambulance records for North Dakota from 1995 to 2000 were used.
      One hundred fifty-six cases of pediatric head injuries with Glasgow Coma Scale
      scores < or =12 and transported by rural ambulance squads were selected. A
      logistic regression analysis was conducted to identify a set of significant
      predictors of cases of inappropriate deliveries to acute care facilities with no
      trauma-center designation of any level (II-V). RESULTS: Greater distance (mean =
      19.96 miles) to the nearest trauma center and shorter distance traveled by the
      ambulance squad to the receiving facility (mean = 19.07 miles) corresponded to
      higher probabilities of mistriage, especially when a child was Native American
      (16 times more likely) and the transportation was conducted in the winter (9
      times more likely). CONCLUSIONS: Timely delivery of pediatric trauma patients to
      designated trauma centers is encumbered in the winter, particularly in Native
      American communities, because of the greater traveling distances, which could be
      counteracted by better mobilization of available resources aimed at
      administration of optimal trauma care.

PMID- 16092305
TI  - Pattern of congenital orthopaedic malformations in an African teaching hospital.
AB  - BACKGROUND: Congenital Orthopaedic malformations are common malformations that
      are usually unacceptable to the common populace in the West African sub-region.
      There is paucity of knowledge about the common types of Orthopaedic congenital
      malformations in our environment This study was undertaken to determine the
      pattern of congenital Orthopaedic malformations in a Teaching Hospital. STUDY
      DESIGN: This was a prospective study of all the Orthopaedic congenital
      malformations seen in our surgical outpatient departments and the inpatient
      referrals from the wards between January 1995 and December 2003. RESULT: There
      were 284 patients in total with a male to female ratio of 2:1 and age range
      between two days to nine years. Clubfoot (CTEV) accounted for 52.8% of all the
      malformations while Congenital knee dislocation (CDK) and calcaneovalgus
      deformity accounted for 8%. Congenital hip dislocation (CDH) accounted for only
      2.2% of all the cases. CONCLUSION: Congenital talipes equinovarus deformity is
      the most common congenital orthopaedic malformation in this environment while
      congenital hip dislocation (CDH) is rare when compared with the Caucasians.

PMID- 16092306
TI  - Ocular findings seen among the staff of an institution in Lagos, Nigeria.
AB  - BACKGROUND: The degree to which ocular morbidity affects workers productivity in
      the developing countries has not been studied adequately. A federal government
      research institute based in Lagos introduced an annual health screen for all its
      workers, which included eye tests. This provided an opportunity to study the
      pattern of ocular conditions among workers who were 30 years and above, and to
      determine the effect of eye diseases on the workers productivity. STUDY DESIGN:
      Detailed eye examination including refraction, was done on every respondent at
      the institution's clinic by an ophthalmologist. A questionnaire on ocular health
      status and occupational history was administered independently by an ophthalmic
      nurse. Sickness absenteeism, use of the clinic were obtained from clinic records,
      and the results were analysed. RESULTS: The common ocular conditions were
      uncorrected or poorly corrected refractive error, uncorrected or poorly corrected
      presbyopia and allergic. conjunctivitis. Glaucoma, maculopathy and optic atrophy
      were causes of severe visual impairment or blindness in 1.9 % of the subjects.
      Absenteeism and clinic use were more common in subjects with ocular morbidity
      than those with non-ocular morbidity. Subjects with ocular morbidity had more
      illnesses, absenteeism and used the clinic more. CONCLUSION: Ocular problems
      which reduce worker's productivity are prevalent among the staff of the
      institution studied. They are mostly unrecognised.

PMID- 16092307
TI  - Molecular epidemiology of methicillin-resistant Staphylococcus aureus in Ilorin,
      Nigeria.
AB  - BACKGROUND: Nosocomial infections caused by methicillin-resistant strains of
      Staphylococcus aureus constitute significant epidemiologic problems. Defining an
      outbreak requires the use of rapid and highly discriminatory epidemiologic
      methods to determine the epidemic strains involved in such outbreak. STUDY
      DESIGN: A descriptive laboratory based surveillance study for MRSA was
      undertaken. One hundred and forty seven Staphylococcus aureus isolates from
      clinical specimens were screened for methicillin resistance at the University of
      Ilorin Teaching Hospital between January and December 2001. Fifty one (34.7%)
      methicillin resistant strains recovered were epidemiologically characterized
      using Eco R1 restriction enzyme analysis of their plasmid DNAs. RESULT: Forty
      five (88.2%) MRSA isolates were associated with infections and 6 (11.8 %) were
      colonizing strains; 36 (70.6%) and 15 (29.4%) were hospital and community
      acquired respectively. Skin and soft tissues were sites of infection in 36 (70.6
      %) cases and surgical, emergency and ICU accounted for 33 (64.7%) isolates. All
      isolates were resistant to more than two antibiotics but sensitive to vancomycin.
      Forty two (82.4 %) isolates contained plasmids including 9 (21.4 %) that
      contained more than one plasmid. Restriction Enzyme Analysis of the Plasmid DNA
      (REAP) divided the isolates into 9 Eco R1 profiles, with profile 2 accounting for
      41.7% of all nosocomial infections in the wards, implying that it is endemic. The
      remaining nosocomial profiles occurred less frequently, suggesting that they are
      sporadic strains originating from outside the hospital. The community strains
      showed diverse digestion pattern indicating that they are from different clones.
      CONCLUSION: The spread of MRSA can be controlled through reinforcement of
      appropriate use of antibiotics, hand washing and laboratory surveillance for
      MRSA, particularly in the surgical wards and intensive care units, in order to
      identify sources of outbreaks.

PMID- 16092308
TI  - Chronic hepatitis in Nigerian patients: a study of 70 biopsy-proven cases.
AB  - BACKGROUND: Liver cirrhosis and hepatocellular carcinoma are known sequelae of
      chronic hepatitis. Early diagnosis and treatment of chronic hepatitis could delay
      or even abort progression to terminal liver disease. STUDY DESIGN: Prospective
      study of 70 consecutive patients with features of early liver disease or
      discovered with HBsAg (or anti-HCV) during pre-employment and/ or pre-donation
      screening at Ile-Ife, Nigeria. All the patients had liver biopsy and the
      histology evaluated with the Knodell Histological Activity Index. RESULT: Fifty
      three patients had symptomatic disease (M: F ratio, 1.5:1) while 17 were
      asymptomatic (M: F ratio, 3:1). The mean ages were 49.04 (SD+/-16.78) and 29.82
      (SD+/-6.13) for the symptomatic and the asymptomatic patients respectively (P<
      0.005). Major symptoms were right upper abdominal pain (68%), weight loss (51%)
      and fatigue (41.5%). Alcohol consumption was significantly related to symptomatic
      chronic hepatitis (P< 0.01). Over 50 % of patients with asymptomatic chronic
      hepatitis had abnormal liver scan and liver function tests. All the asymptomatic
      cases and 77.4 % of the symptomatic group had HBsAg while only 1 patient
      (symptomatic) was anti-HCV positive. On liver histology, all the patients with
      asymptomatic chronic hepatitis had a Knodell score of< or = 8 and none had
      fibrosis. Over half of the symptomatic patients had a Knodell score of > or = 9
      (56.6%) and stage 2 or 3 fibrosis (51 %). CONCLUSION: Asymptomatic chronic
      hepatitis patients tend to be younger and of the male sex. Symptomatic chronic
      hepatitis may signal the onset of significant fibrosis and alcohol abuse may
      accelerate this process. Serum ALT and liver scan are useful initial screening
      tests for asymptomatic patients with hepatitis B or C viral markers.

PMID- 16092309
TI  - Congenital eye anomalies in Enugu, South-Eastern Nigeria.
AB  - OBJECTIVES: To determine the types of congenital ocular anomalies seen in the eye
      clinic of the University of Nigeria Teaching Hospital Enugu, over an 8-year
      period from January 1992 to December 1999. METHOD: In a retrospective non
      comparative case-series study, the records of all patients with congenital ocular
      anomalies seen between January 1992 and December 1999, were analysed for types of
      anomalies, aetiology, sex and ages at presentation of all patients. RESULTS: A
      total of 54 cases were analysed: 25 females; 29 males (M:F = 1: 1.2). Congenital
      cataract was the most frequently occurring congenital ocular anomaly (42.6%);
      followed by congenital glaucoma (22.2%) and anophthalmia/microphthalmia and
      congenital esotropia (9.3%) each. CONCLUSION: In spite of the limitations of this
      study our findings are similar to those in other studies.

PMID- 16092310
TI  - A comparative study of the haemodynamic effects of atropine and glycopyrrolate at
      induction of anaesthesia in children.
AB  - BACKGROUND: Bradycardia following administration of halothane and suxamethonium
      in children leads to reduced cardiac output, which can be prevented with
      prophylactic anticholinergics. Anticholinergics may result in tachycardia and
      arrhythmias. This study was designed to compare haemodynamic changes and
      incidence of cardiac arrhythmias following intravenous atropine and
      glycopyrrolate. STUDY DESIGN: Ninety ASA I and II children between one month and
      twelve years were studied. Premedication was with oral promethazine 1mg/kg.
      Anaesthesia was achieved with 3 % halothane in 33 % oxygen and nitrous oxide.
      Patients were randomly allocated to receive atropine 0.01mg/kg (Group I) or
      glycopyrrolate 0.005mg/kg (Group II). Tracheal intubation was facilitated with
      suxamethonium 1.5mg/kg. RESULTS: Patients in Group I had a 35.7% rise in heart
      rate from baseline, compared to 22.5 % in Group II two minutes after
      anticholinergic administration (p=0.001). Following intubation, heart rate rose
      by 9.7 % and 13.2 % (p<0.05) in Groups I and II respectively. MAP rose similarly
      in both groups. Arrhythmia occurred in 44.4 % of patients in Group I and 11.1% in
      Group II (p=0.001) and were mainly sinus tachycardia. 2.2% of patients in Group I
      exhibited bigemini. No patient experienced bradycardia. Hypoxia occurred in 2.2
      %, hypotension in 13.3% and mild laryngeal spasm in 0% of Group I and 11.1%, 4.4%
      and 4.4% of Group II respectively. CONCLUSION: The use of glycopyrrolate compared
      to atropine, offered better cardiovascular stability in Nigerian children.
      Arrhythmias occurred more in patients who had atropine and occurred most
      frequently after tracheal intubation.

PMID- 16092311
TI  - Serum magnesium, phosphate and calcium in Nigerian children with sickle cell
      disease.
AB  - BACKGROUND: Biochemical abnormalities have been associated with sickle cell
      disease. Studies on phosphorus and magnesium in sickle cell disease have been
      conflicting. There is paucity of information on the role of these ions in the
      pathogenesis and management of sickle cell disease. This study was set out to
      determine the serum levels of magnesium, phosphorus and calcium in Nigerian
      children with sickle cell disease. STUDY DESIGN: A case-control study carried out
      on children with HbSS genotype (cases) and age-matched controls with HbAA. Serum
      magnesium, calcium, phosphorus and albumin were measured using colorimetric
      methods. RESULTS: Eighty-six subjects and forty-five controls were studied. The
      mean serum magnesium was 0.99mmol/L (0.02) and 0.98mmol/L (0.02) in the cases and
      controls respectively. The difference was not significant. Mean serum calcium was
      significantly lower in the cases [2.1mmol/L (0.3)] compared with the controls
      [2.3mmol/ L (0.15)]; p<0.01. Serum phosphorus was significantly higher in the
      cases than in the controls [2.2mmol/L (0.7) versus (1.5mmol/L (0.6); p<0.001].
      There was no statistical difference in the albumin binding of calcium in both
      groups. A positive correlation existed between serum phosphorus and magnesium and
      also between serum calcium and magnesium in the cases group but no correlation
      between these parameters and age was found. CONCLUSION: Children with sickle cell
      anaemia in this study had normo-magnesaemia, hyperphosphataemia and
      hypocalcaemia. Further studies on changes in intracellular concentrations of
      these ions in children with sickle cell disease are required. Such findings could
      be useful in designing better management in individuals with this abnormality.

PMID- 16092312
TI  - Usefulness of acute phase proteins for monitoring development of hepatocellular
      carcinoma in hepatitis B virus carriers.
AB  - BACKGROUND: Serum levels of acute phase proteins (APP) have been used to diagnose
      and follow up treatment of liver diseases. This study was carried out to
      determine the usefulness of APP to predict development of hepatocellular
      carcinoma (HCC) among Hepatitis B virus (HBV) carriers. STUDY DESIGN: In a
      prospective study, serum haptoglobin, transferrin and alpha 2 macroglobulin
      levels of 55 subjects consisting of 20 HBV carriers, 18 HBV-positive HCC patients
      and 17 controls were determined using single radial immunodiffusion. RESULT: The
      mean levels of haptoglobin were 141.75mg/dl+/-133.76, 97.11mg/dl+/
      92.62,161.59mg/dl+/-146.86 for HBV carriers, HBV-positive HCC and controls
      respectively. The mean transferrin levels for HBV carriers, HBV-positive HCC and
      controls were 166.4mg/ dl+/-88.31, 140.0mg/dl+/-68.73 and 270.35mg/dl+/-122.79
      respectively while similar values for alpha 2 macroglobulin were 195.4mg/dl+/
      93.86, 189.83mg/dl+/-77.19 and 127.53mg/dl+/-43.29. No significant difference in
      the mean serum haptoglobin levels of HBV carriers and HBV-positive HCC (p=0.526),
      HBV carriers and controls (p= 0.883) and HBV-positive HCC and controls (p=0.295).
      The difference between the mean serum transferrin levels was insignificant
      between HBV carriers and HBV-positive HCC, p= 0.671, but was significant between
      HBV carriers, and HBV-positive HCC compared with controls, (p=0.005 and 0.000
      respectively). No significant difference in alpha 2 macroglobulin between HBV
      carriers and HBV-positive HCC, (p=0.972), but the differences were significant
      between HBV carriers, and HBV-positive HCC and controls, (p=0.024 and 0.048
      respectively). CONCLUSION: Haptoglobin, alpha 2 macroglobulin and transferrin
      lack predictive value for development of HCC in HBV carriers. Reduced transferrin
      and increased alpha 2 macroglobulin in HBV carriers might suggest active liver
      disease.

PMID- 16092313
TI  - Double blind clinical trial comparing the safety and efficacy of nimesulide
      (100mg) and diclofenac in osteoarthrosis of the hip and knee joints.
AB  - BACKGROUND: Osteoarthritis of the hip or knees is a very disabling condition in
      both Caucasians and Africans. A lot of medical drugs have been in use with their
      corresponding side effects, hence the search for newer drugs with fewer side
      effects. STUDY DESIGN: A double blind clinical trial comparing the safety and
      efficacy of nimesulide and diclofenac was carried out in the University College
      Hospital Ibadan. All patients referred to the outpatients department of the
      orthopaedic division with osteoarthritis of the hips and knees who met the
      criteria for inclusion in the study were used for the study. RESULTS: There were
      a total number of sixty-seven (67) patients. 70.6% of the nimesulide patients had
      only mild pain in the involved joint on completion of the eight weeks trial
      compared to 50% of the diclofenac group. A significant proportion of the patients
      in the diclofenac group (50% vs 17.6%) had break through pain that warranted the
      use of at least two tablets of 500mg of paracetamol per week in contrast to the
      nimesulide group. There was a statistically significant difference in the
      frequency of side effects between the patients in the diclofenac group and the
      nimesulide group (p<0.05). CONCLUSION: Nimesulide was found to be more effective
      in relieving pain in osteoarthritis of the hip and knees and with less side
      effects than diclofenac.

PMID- 16092314
TI  - Assessment for markers of nephropathy in newly diagnosed type 2 diabetics.
AB  - BACKGROUND: Type 2 diabetics account for a large proportion of patients
      presenting in end-stage kidney disease (ESKD). Although diabetic renal disease
      can be predicted, a lot of diabetics present to Nephrologists in ESKD. OBJECTIVE:
      To assess for markers of nephropathy in newly diagnosed type 2 diabetics, using
      blood pressure levels, endogenous creatinine clearance and urinary protein
      excretion as markers of renal disease. STUDY DESIGN: Ninety newly diagnosed type
      2 diabetics were studied within 6 weeks of diagnosis. They were in good glycaemic
      control during the period of study. Seventy-two age and sex-matched and
      apparently healthy non-diabetics served as controls. Blood pressure was recorded
      in all subjects. 24 hours urine sample was collected for estimation of urinary
      protein excretion and endogenous creatinine clearance. RESULTS: Systolic and
      diastolic blood pressures were consistently higher in diabetics than in controls
      (p=0.001 and p=0.001 respectively). High-normal and midly elevated blood pressure
      were more prevalent in diabetics (p=0.001). Mean creatinine clearance in
      diabetics was significantly lower than in non-diabetics (p=0.037). 7 % of
      diabetics had supra-normal creatinine clearance of >125mls/minute. The prevalence
      of microproteinuria was 40% in diabetics and 33% in non-diabetics, while
      macroproteinuria was present in 44% of diabetics but absent in non-diabetics
      (p=0.000). CONCLUSION: High-normal, mildly elevated blood pressure and
      microproteinuria were commonly encountered in newly diagnosed diabetics studied.
      The phenomenon of hyperfiltration was present in type 2 diabetics. These tools
      should be assessed at diagnosis of diabetes as this will help in identifying
      those who are at an increased risk for developing diabetic nephropathy.

PMID- 16092315
TI  - Burkitt's lymphoma of the head and neck region in a Nigerian tertiary hospital.
AB  - BACKGROUND: Burkitt's lymphoma is endemic in Nigeria; it forms about 39% of all
      childhood cancers. In recent times more of these cases are being seen presenting
      first to the Ear Nose and Throat clinic. OBJECTIVE: This study is designed to
      look at the pattern of presentation of head and Neck Burkitt's lymphoma at a
      Nigerian Tertiary hospital and to evaluate current treatment modality. DESIGN: It
      is a retrospective study of all confirmed Burkitt's lymphoma of the head and neck
      region seen at the Obafemi Awolowo University Teaching Hospital Ile Ife (OAUTHC)
      between 1986 and 2002. PATIENTS AND METHODS: The medical records of all the
      patients with the histopathologically confirmed Burkitt's lymphoma over a 17-year
      period (1986-2002) were evaluated. The proportion of the tumor affecting the Head
      and neck region were noted. The data extracted were entered into a questionnaire
      and analysis of data was done using the SPSS 10.0 software. RESULTS: A total of
      196 cases of Burkitt's lymphoma were seen over the period out of which 140
      (71.4%) were in the head and neck region. There was a male preponderance with the
      incidence of 72% and 28% in females. The peak age incidence was found to be
      within the first decade of life. The most common sites that were affected are;
      the jaw (65.9%), nasal and paranasal sinuses (12.2). Majority of the patients
      presented with advanced disease. Combination Chemotherapy comprising
      Cyclophosphamide, Oncovin, Methotrexate and Prednisolone (COMP) was the mainstay
      of management. The treatment outcome was only favorable in 36.6%. Default rate
      was (11.7%) while the mortality rate was (12.6%). Relapse?recurrence was found in
      (5.1%) of cases. Frank drug resistance was found in (2.6%). Blindness was found
      to be a major morbidity associated with this disease. Septicemia and severe
      anemia were found to be the major causes of mortality. Some complications of
      treatment were noted. DISCUSSION: The importance of the findings in this work was
      discussed in line with the existing literature. CONCLUSION: Head and neck remain
      the mostly affected parts in Burkitt's lymphoma in this environment. Presentation
      with advanced disease is the bane. This partly explains high morbidity and
      mortality in affected children.

PMID- 16092316
TI  - Hernia repair under local or intravenous Ketamine in a tropical low socio
      economic population.
AB  - BACKGROUND: All over the world hernia surgery constitutes a significant portion
      of the operations performed by a general surgeon. Operations for hernias ideally
      should be within the purview of secondary health centres thus allowing the
      tertiary health centres to focus on research and/or manage unusual or difficult
      presentations of diseases. STUDY DESIGN: This prospective study reviews the
      management of hernias in the Catholic hospital Oluyoro in Ibadan by recording the
      demographic data, hernia characteristics and operations performed on 98
      paediatric and 171 adult hernia patients who presented to the hospital between
      April 1996 and October 1998 with the use of intravenous Ketamine or local
      infiltration with xylocaine. RESULTS: In a 30-month period from April 1996 to
      October 1998, the author operated on 98 paediatric and 171 adult hernia patients.
      There were no paediatric mortalities but there was 1 adult mortality. CONCLUSION:
      This paper shows that hernia operations in paediatric and adult patients can be
      safely done under intravenous Ketamine or local infiltration with xylocaine
      injection in a secondary care health institution.

PMID- 16092317
TI  - The ultrastructure of the peri-articular osteophytes - an evaluation by scanning
      electron microscopy.
AB  - OBJECTIVE: Osteophytes are intra-articular osteochondral tissues, which are
      usually found at the margins of degenerating synovial joints. The aetiology or
      pathogenesis of this tissue has been a subject of protracted debate. The aim of
      this study was to offer a possible aetiology and or pathogenesis of this
      expendable yet important osteochondral tissue using the scanning electron
      microscopy to evaluate the structure of the cartilage mantle of osteophytes and
      the relationship of this mantle with that of the adjoining normal articular
      cartilage. METHODS: Sections of periarticular osteophytes and osteophyte-normal
      articular cartilage composite tissues were obtained during total knee replacement
      for osteoarthritis (OA). These sections were routinely processed and examined
      using the scanning electron microscope with emphasis on the osteophytic cartilage
      mantle and the merger of the osteophyte and the adjoining normal articular
      cartilage. RESULTS: The cartilage mantle of osteophytes was found to be thinner
      but continuous with that of the adjoining normal articular cartilage. However, a
      longitudinal bar of acellular tissue was found to separate the subchondral bones
      of both tissues. The cellular (chondrocyte) arrangement in the osteophytic
      cartilage was similar to that of the adjoining normal articular cartilage. In
      addition, in the superficial layer, there was looping of collagen fibres between
      the normal articular cartilage mantle and that of the osteophytic tissues.
      CONCLUSION: The continuity between the cartilage mantle of osteophytes and the
      adjoining normal articular cartilage may suggest that in the formation of
      osteophytes, the chondrocytes from the adjoining normal articular cartilage
      greatly influence the mesenchymal tissue precursor of osteophyte to differentiate
      along a chondrocytic pathway initially. With subsequent vascular invasion
      probably from the periosteum, the neocartilage develops a bony core with a
      completely separate blood supply from that of the adjoining subchondral bone.

PMID- 16092318
TI  - Normative data on mental and motor development in Nigerian children.
AB  - BACKGROUND: In Nigeria and sub-Saharan Africa at large, there has been heavy
      reliance on the "Caucasian data" in the developmental assessment of children.
      Hence, this study set out to establish normative data for psychomotor development
      on Nigerian children. STUDY DESIGN: One hundred and twenty eight children
      distributed equally to eight different integrative age groups between 8 weeks and
      30 months were included in the cross-sectional study. The subjects were assessed
      for the five fields of development using Developmental Screening Inventory (DSI)
      and Bayley Scales of Infant Development (BSID): a screening and performance
      instruments respectively. A trained research assistant administered the DSI on
      each of the subjects, and the scores made blind to the researchers until after
      the subject's assessment with the BSID within maximum of 24 hours interval.
      RESULTS: The subjects scored above the normal values in the five fields of
      development for each of the instruments. Furthermore, from the normative data
      derived, there were high scores in the motor and personal -social fields,
      especially among subjects in the lower age groups of 8,16,and 32 weeks when
      compared to data from the western world. CONCLUSION: It is concluded that this
      normative data will be of much clinical value to practitioners in Nigeria,
      especially the pediatricians, psychiatrists, clinical psychologists, etc.

PMID- 16092319
TI  - Adult tetanus in Accra, why the high mortality? An audit of clinical management
      of tetanus.
AB  - BACKGROUND: Tetanus is a life threatening infection relatively uncommon in the
      developed countries but occurs frequently in developing countries with case
      fatality rates of 40-60 %. Recent review of adult tetanus at the Korle-bu
      Teaching Hospital showed a high case fatality of 50%. In order to determine the
      factors underlying this high case fatality we conducted a retrospective clinical
      audit of the clinical management of adult tetanus admitted in 1994 to 2001 to the
      Korle-bu Teaching Hospital. METHODS: Data extracted from the admission and
      discharge books of the Fevers' Unit of Korle-bu Teaching Hospital, Accra and
      patient case notes were examined and analysed. RESULTS: Case fatality rate (CFR)
      varied from 25 % in 1999 to 72.7% in 2001. There was no gender difference in the
      case fatality. There was no significant difference in the mean age of those who
      died and those who survived, however, the CFR rose with age. The presence of neck
      and a dirty wound were associated with increased CFR. The CFR correlated with the
      severity of tetanus and increased when an expected treatment action, wound
      debridement, administration of antibiotics and/or immunoglobulin, was not
      performed. The administration of anti-tetanus toxin was associated with an
      increased CFR. CONCLUSION: The high case fatality rate in Accra was due to
      inappropriate management with most of the patients not treated with
      immunoglobulin and antibiotics and had inadequate wound care.

PMID- 16092320
TI  - Tear break-up time in eyes with pterygia and pingueculae in Ibadan.
AB  - BACKGROUND: Ultraviolet (UV) rays and chronic irritation to dust have been
      implicated in the pathogenesis of degenerative conditions of the cornea and
      conjunctiva like pterygium and pinguecula. It has been postulated that exposure
      to these environmental factors cause corneal and conjunctival drying by
      disruption of the tear film. While some researchers have found tear film
      dysfunction in eyes with pterygia and pingueculae, others have found no such
      abnormalities. The differences in findings may be due to different methods of
      investigation, or differences based on geography and climate. STUDY DESIGN: The
      tear film has been studied using tear break-up time (TBUT) in adults with
      pterygia and pingueculae disorders, TBUT was measured in 73 eyes with pterygia
      and 74 eyes with pinguecula and were compared to TBUT in 74 eyes of age and sex
      matched normal controls. Abnormal TBUT was defined as TBUT less than 15 secs.
      Unstable tear film was defined as TBUT less than 10 secs. RESULTS: The mean TBUT
      was lower in eyes with pterygia (17.90 secs) than in control eyes (19.86 secs),
      although the mean difference was not statistically significant. Abnormal TBUT,
      defined as TBUT less than 15 secs, was found in 29 eyes out of 73 eyes with
      pterygia (39.7%), compared with 13 eyes out of 74 eyes with pingueculae (17.6%)
      and in 17(23.0%) of 74 control eyes (X2 = 10.01, df = 2, P = 0.0006). A TBUT of
      less than 15 secs was more significantly associated with eyes with pterygia
      compared to control eyes. Unstable tear film (TBUT less than 10 secs) was found
      in 12(16.4%) eyes with pterygia, compared to 4(5.4%) eyes with pingueculae and
      4(5.4%) control eyes. Unstable tear film was significantly associated with eyes
      with pterygia (P = 0.027). CONCLUSION: Tear film abnormalities are associated
      with pterygium but not with pinguecula in the subjects studied. TBHT may vary in
      different populations.

PMID- 16092321
TI  - Risk of nosocomial bacteria transmission: evaluation of cleaning methods of
      probes used for routine ultrasonography.
AB  - BACKGROUND: There exists a small but definite risk of nosocomial infection
      transmission attributable to ultrasonography probes and coupling gels. OBJECTIVE:
      Our objective was to ascertain whether the current method of probe disinfection
      in between patients is adequate to prevent cross infection, and to determine the
      best and safest method of probe disinfection applicable during routine
      ultrasonography in our institution. MATERIALS AND METHOD: Forty consecutive
      patients sent for routine ultrasonography at the Radiology Department of our
      institution in the month of January 2004 were studied. Each patient had a
      standardized ultrasound scan of the abdomen, after which swabs were taken from
      the surface of the unclean probe and after probe disinfection by single and
      double paper wipe cleaning method. The swabs were cultured on Blood agar to
      determine the characteristics of the colony forming units (CFU). RESULT: Forty
      four bacterial isolates were recovered from 37 patients who cultured positive,
      with MRSA constituting 36.4 %, MRCONS 22.7 %, MSSA 13.6 %, MSCONS 13.6%,
      Klebsiella spp 9.1% and Proteus mirabilis 4.6%. The average CFU transmitted by
      the unclean probe was significantly higher (P<0.05) than that transmitted by the
      probe after single or double paper wipe. Also, the average CFU transmitted
      following single and double paper wipe, in the inpatients was significantly
      higher (P<0.05) than in the outpatients. CONCLUSION: Single paper wipe is
      adequate for outpatients, but for inpatients, especially those with high risk of
      cross infection, double paper wipe is preferred with probe thoroughly wiped until
      visibly clean.

PMID- 16092322
TI  - Agitation in the medically ill elderly.
AB  - Agitation is a common and significant problem in the medically ill elderly. It is
      responsible for diminished quality of life for not only the patient, but the
      caregivers as well as the patient's relatives. This paper will illustrate the
      concept of agitation and different modes of classification. The major emphasis
      will be placed on discussing prompt, correct diagnosis of the underlying cause of
      agitation and effective treatment of both the cause of agitation and the symptoms
      of agitation itself.

PMID- 16092323
TI  - A five-year review of childhood mortality at the University College Hospital,
      Ibadan.
AB  - INTRODUCTION: The present study sought to provide a comprehensive description of
      causes of mortality in a local Nigerian children population as a measure of their
      health status. METHODS AND PATIENTS: A retrospective study of the pattern of
      mortality among 12,522 children admitted into all the six wards of the department
      of Paediatrics, University College Hospital, Ibadan during a five-year period
      (January 1996 - December 2000) was done. RESULTS: There were 1,185 deaths with an
      overall mortality rate of 9.5 per cent. There was no significant change in
      childhood mortality rate over the five years reviewed. Of the 1185 deaths, 48.8 %
      occurred within 24 hours and neonatal deaths accounted for 50.8 % of the total
      number of deaths. The leading causes of death were neonatal tetanus,
      Prematurity/low birth weight, neonatal septicaemia, severe birth asphyxia,
      meningitis, severe malaria, pneumonia, septicaemia, severe malnutrition, and
      measles. Deaths from sickle cell anaemia were found only among children above 5
      years of age. CONCLUSIONS: Majority of deaths occurred in neonates and were
      preventable.

PMID- 16092324
TI  - Pancreatic carcinoma presenting as cutaneous nodules in a diabetic Nigerian male.

PMID- 16092325
TI  - Transverse leukonychia: a case report.
AB  - A case of transverse leukonychia following chemotherapy for Hodgkin's disease in
      a 17-year-old white male is reported. The patient presented with multiple white
      bands across the fingernails, which appeared three weeks after the end of
      chemotherapy. The changes were almost homogeneously spread across the breadth of
      the fingernail plates, showing smooth borders with a rounded distal edge. Because
      of Hodgkin's disease in Costwold stage IE, he received sequential chemotherapy
      with cyclophosphamide, adriamycin, procarbazine, prednisolone, vincristine and
      bleomycine, and mediastinal mass irradiation. The authors emphasize that white
      transverse nail banding - Leukonychia striata or Muehrcke lines - constitute an
      aesthetical unpleasant side-effect of medication, but may represent an easily
      observed sign indicative of previous use of cytotoxic therapy for malignancy.

PMID- 16092326
TI  - Delineating fluid-filled region boundaries in optical coherence tomography images
      of the retina.
AB  - We evaluate the ability of a deformable model to yield accurate shape
      descriptions of fluid-filled regions associated with age-related macular
      degeneration. Calculation of retinal thickness and volume by the current optical
      coherence tomography (OCT) system includes fluid-filled regions or lesions along
      with actual retinal tissue. In order to quantify these lesions independently from
      the retinal tissue, they must be outlined. A deformable model was applied to OCT
      images of retinas demonstrating cystoids and subretinal fluid spaces. Several
      implementation issues were addressed in order to choose appropriate parameters.
      The use of a nonlinear anisotropic diffusion filter to suppress speckle noise
      while at the same time preserving the edges of the original image was explored.
      Once the contours of the lesions were outlined, quantitative analysis of the
      surface area and volume of the lesions was performed. The deformable model could
      accurately outline fluid-filled regions within the retina. The detection method
      tested proved effective in capturing the complexity of fluid-filled regions in
      OCT images. Deformable models combined with nonlinear anisotropic diffusion
      filtering show promise in the detection of retinal features of interest for
      diagnosis in clinical OCT images. Thus, fluid-filled region detection may
      significantly aid in analysis of treatments and diagnosis.

PMID- 16092327
TI  - The bi-elliptical deformable contour and its application to automated tongue
      segmentation in Chinese medicine.
AB  - Automated tongue image segmentation, in Chinese medicine, is difficult due to two
      special factors: 1) there are many pathological details on the surface of the
      tongue, which have a large influence on edge extraction; 2) the shapes of the
      tongue bodies captured from various persons (with different diseases) are quite
      different, so they are impossible to describe properly using a predefined
      deformable template. To address these problems, in this paper, we propose an
      original technique that is based on a combination of a bi-elliptical deformable
      template (BEDT) and an active contour model, namely the bi-elliptical deformable
      contour (BEDC). The BEDT captures gross shape features by using the steepest
      decent method on its energy function in the parameter space. The BEDC is derived
      from the BEDT by substituting template forces for classical internal forces, and
      can deform to fit local details. Our algorithm features fully automatic
      interpretation of tongue images and a consistent combination of global and local
      controls via the template force. We apply the BEDC to a large set of clinical
      tongue images and present experimental results.

PMID- 16092328
TI  - A new path planning algorithm for maximizing visibility in computed tomography
      colonography.
AB  - In virtual colonoscopy, minimizing the blind areas is important for accurate
      diagnosis of colonic polyps. Although useful for describing the shape of an
      object, the centerline is not always the optimal camera path for observing the
      object. Hence, conventional methods in which the centerline is directly used as a
      path produce considerable blind areas, especially in areas of high curvature. Our
      proposed algorithm first approximates the surface of the object by estimating the
      overall shape and cross-sectional thicknesses. View positions and their
      corresponding view directions are then jointly determined to enable us to
      maximally observe the approximated surface. Moreover, by adopting bidirectional
      navigations, we may reduce the blind area blocked by haustral folds. For
      comfortable navigation, we carefully smoothen the obtained path and minimize the
      amount of rotation between consecutive rendered images. For the evaluation, we
      quantified the overall observable area on the basis of the temporal visibility
      that reflects the minimum interpretation time of a human observer. The
      experimental results show that our algorithm improves visibility coverage and
      also significantly reduces the number of blind areas that have a clinically
      meaningful size. A sequence of rendered images shows that our algorithm can
      provide a sequence of centered and comfortable views of colonography.

PMID- 16092329
TI  - Partial volume effect compensation for quantitative brain SPECT imaging.
AB  - Partial volume (PV) effects degrade the quantitative accuracy of SPECT brain
      images. In this paper, we extended a PV compensation (PVC) method originally
      developed for brain PET, the geometric transfer matrix (GTM) method, to brain
      SPECT using iterative reconstruction-based compensations. In the GTM method a
      linear transform between the true regional activities and the measured results
      was assumed. Elements of the GTM were calculated by projecting and reconstructing
      maps with uniform regions representing different structures. However, with
      iterative reconstruction methods, especially when reconstruction-based
      compensation for detector response was applied, we found that it was important to
      treat the region maps as a perturbation to the reconstructed image in the
      estimation of the GTM. This modified method, termed perturbation-based GTM (pGTM)
      was evaluated using Monte Carlo (MC) simulated and experimentally acquired data.
      Results showed great improvement of the quantitative accuracy in brain SPECT
      imaging. For MC simulated data, PVC using pGTM reduced the underestimation of
      striatal activities from 30% to less than 1.2%. For experimental data, PVC using
      pGTM reduced the underestimation of striatal activities from 36% to less than
      7.8%. The underestimation of the striatum to background activity ratio was also
      improved from 31% to 2.7%.

PMID- 16092330
TI  - EnPiT: filtered back-projection algorithm for helical CT using an n-Pi
      acquisition.
AB  - In this paper, we formulate a reconstruction algorithm for an n-Pi acquisition,
      where n can be any positive odd integer. The algorithm is a generalization of the
      method presented in (Bontus et al. 2003). It is based on the results obtained by
      Katsevich (2004). For the algorithm, different sets of filter-lines have to be
      defined. We describe the variation of these lines along the detector in some
      detail, before we discuss, how the method gives all Radon-plane contributions the
      correct weighting. The different sets of filter-lines are all contained within
      the n-Pi window, such that a practical realization is possible. Reconstruction
      results, which we present in the final section, show convincing image quality.

PMID- 16092331
TI  - Neural networks approach to clustering of activity in fMRI data.
AB  - Clusters of correlated activity in functional magnetic resonance imaging data can
      identify regions of interest and indicate interacting brain areas. Because the
      extraction of clusters is computationally complex, we apply an approximative
      method which is based on artificial neural networks. It allows one to find
      clusters of various degrees of connectivity ranging between the two extreme cases
      of cliques and connectivity components. We propose a criterion which allows to
      evaluate the relevance of such structures based on the robustness with respect to
      parameter variations. Exploiting the intracluster correlations, we can show that
      regions of substantial correlation with an external stimulus can be unambiguously
      separated from other activity.

PMID- 16092332
TI  - An estimation/correction algorithm for detecting bone edges in CT images.
AB  - The normal direction of the bone contour in computed tomography (CT) images
      provides important anatomical information and can guide segmentation algorithms.
      Since various bones in CT images have different sizes, and the intensity values
      of bone pixels are generally nonuniform and noisy, estimation of the normal
      direction using a single scale is not reliable. We propose a multiscale approach
      to estimate the normal direction of bone edges. The reliability of the estimation
      is calculated from the estimated results and, after re-scaling, the reliability
      is used to further correct the normal direction. The optimal scale at each point
      is obtained while estimating the normal direction; this scale is then used in a
      simple edge detector. Our experimental results have shown that use of this
      estimated/corrected normal direction improves the segmentation quality by
      decreasing the number of unexpected edges and discontinuities (gaps) of real
      contours. The corrected normal direction could also be used in postprocessing to
      delete false edges. Our segmentation algorithm is automatic, and its performance
      is evaluated on CT images of the human pelvis, leg, and wrist.

PMID- 16092333
TI  - An automated method for analysis of flow characteristics of circulating particles
      from in vivo video microscopy.
AB  - The behavior of white and red blood cells, platelets, and circulating injected
      particles is one of the most studied areas of physiology. Most methods used to
      analyze the circulatory patterns of cells are time consuming. We describe a
      system named CellTrack, designed for fully automated tracking of circulating
      cells and micro-particles and retrieval of their behavioral characteristics. The
      task of automated blood cell tracking in vessels from in vivo video is
      particularly challenging because of the blood cells' nonrigid shapes, the
      instability inherent in in vivo videos, the abundance of moving objects and their
      frequent superposition. To tackle this, the CellTrack system operates on two
      levels: first, a global processing module extracts vessel borders and center
      lines based on color and temporal patterns. This enables the computation of the
      approximate direction of the blood flow in each vessel. Second, a local
      processing module extracts the locations and velocities of circulating cells.
      This is performed by artificial neural network classifiers that are designed to
      detect specific types of blood cells and micro-particles. The motion
      correspondence problem is then resolved by a novel algorithm that incorporates
      both the local and the global information. The system has been tested on a series
      of in vivo color video recordings of rat mesentery. Our results show that the
      synergy between the global and local information enables CellTrack to overcome
      many of the difficulties inherent in tracking methods that rely solely on local
      information. A comparison was made between manual measurements and the
      automatically extracted measurements of leukocytes and fluorescent microspheres
      circulatory velocities. This comparison revealed an accuracy of 97%. CellTrack
      also enabled a much larger volume of sampling in a fraction of time compared to
      the manual measurements. All these results suggest that our method can in fact
      constitute a reliable replacement for manual extraction of blood flow
      characteristics from in vivo videos.

PMID- 16092334
TI  - Toward automated segmentation of the pathological lung in CT.
AB  - Conventional methods of lung segmentation rely on a large gray value contrast
      between lung fields and surrounding tissues. These methods fail on scans with
      lungs that contain dense pathologies, and such scans occur frequently in clinical
      practice. We propose a segmentation-by-registration scheme in which a scan with
      normal lungs is elastically registered to a scan containing pathology. When the
      resulting transformation is applied to a mask of the normal lungs, a segmentation
      is found for the pathological lungs. As a mask of the normal lungs, a
      probabilistic segmentation built up out of the segmentations of 15 registered
      normal scans is used. To refine the segmentation, voxel classification is applied
      to a certain volume around the borders of the transformed probabilistic mask.
      Performance of this scheme is compared to that of three other algorithms: a
      conventional, a user-interactive and a voxel classification method. The
      algorithms are tested on 10 three-dimensional thin-slice computed tomography
      volumes containing high-density pathology. The resulting segmentations are
      evaluated by comparing them to manual segmentations in terms of volumetric
      overlap and border positioning measures. The conventional and user-interactive
      methods that start off with thresholding techniques fail to segment the
      pathologies and are outperformed by both voxel classification and the refined
      segmentation-by-registration. The refined registration scheme enjoys the
      additional benefit that it does not require pathological (hand-segmented)
      training data.

PMID- 16092335
TI  - Stereopsis-guided brain shift compensation.
AB  - Brain deformation models have proven to be a powerful tool in compensating for
      soft tissue deformation during image-guided neurosurgery. The accuracy of these
      models can be improved by incorporating intraoperative measurements of brain
      motion. We have designed and implemented a passive intraoperative stereo vision
      system capable of estimating the three-dimensional shape of the surgical scene in
      near real-time. This intraoperative shape is compared with the cortical surface
      in the co-registered preoperative magnetic resonance (MR) volume for the
      estimation of the cortical motion resulting from the open cranial surgery. The
      estimated cortical motion is then used to guide a full brain model, which updates
      a preoperative MR volume. We have found that the stereo vision system is accurate
      to within approximately 1 mm. Based on data from two representative clinical
      cases, we show that stereopsis guidance improves the accuracy of brain shift
      compensation both at and below the cortical surface.

PMID- 16092336
TI  - A method for determination of the timing stability of PET scanners.
AB  - We report on the timing resolution and stability of the MicroPET R4 PET scanner.
      Its detectors have energy resolutions in the range of 25% and previously reported
      timing resolutions 3.2 ns. Our preliminary evaluation of this instrument showed
      that artefact-free normalization sinograms could only be obtained with a timing
      window of 10 ns or more in spite of a timing resolution of 3.2 ns. This
      instrument uses high-speed electronics albeit with 2-ns timing clock. We
      performed sham transmission scans with nothing in the field of view, and a range
      of timing windows from 2 to 14 ns and used a 14-ns timing blank scan to generate
      effective attenuation sinograms as a function of timing window. These showed
      trues count-rates which fit well to a ERF (tau) function. However, the effective
      attenuation value, which should be 1.0, changes from block to block and becomes
      very high in some blocks (> 3.5 at 6 ns) suggesting the need for timing
      alignment. A method was devised to measure the timing stability to a precision
      better than the timing bin width of 2 ns.

PMID- 16092337
TI  - A comparison of a similarity-based and a feature-based 2-D-3-D registration
      method for neurointerventional use.
AB  - Two-dimensional (2-D)-to-three-dimensional (3-D) registration can improve
      visualization which may aid minimally invasive neurointerventions. Using clinical
      and phantom studies, two state-of-the-art approaches to rigid registration are
      compared quantitatively: an intensity-based algorithm using the gradient
      difference similarity measure; and an iterative closest point (ICP)-based
      algorithm. The gradient difference approach was found to be more accurate, with
      an average registration accuracy of 1.7 mm for clinical data, compared to the ICP
      based algorithm with an average accuracy of 2.8 mm. In phantom studies, the ICP
      based algorithm proved more reliable, but with more complicated clinical data,
      the gradient difference algorithm was more robust. Average computation time for
      the ICP-based algorithm was 20 s per registration, compared with 14 min and 50 s
      for the gradient difference algorithm.

PMID- 16092338
TI  - Correction of bias field in MR images using singularity function analysis.
AB  - A new approach for correcting bias field in magnetic resonance (MR) images is
      proposed using the mathematical model of singularity function analysis (SFA),
      which represents a discrete signal or its spectrum as a weighted sum of
      singularity functions. Through this model, an MR image's low spatial frequency
      components corrupted by a smoothly varying bias field are first removed, and then
      reconstructed from its higher spatial frequency components not polluted by bias
      field. The thus reconstructed image is then used to estimate bias field for final
      image correction. The approach does not rely on the assumption that anatomical
      information in MR images occurs at higher spatial frequencies than bias field.
      The performance of this approach is evaluated using both simulated and real
      clinical MR images.

PMID- 16092339
TI  - Optical signal path delay fluctuations caused by atmospheric turbulence.
AB  - We report the first direct measurements, to our knowledge, of optical signal path
      delay fluctuations caused by optical turbulence in the atmosphere. The
      experiments were based on satellite laser ranging. Our initial motivation was to
      identify all the random error contributors in satellite laser ranging. We
      measured and identified the random path fluctuations caused by the atmosphere in
      the range of units of picoseconds. An appropriate fluctuation model was
      developed.

PMID- 16092340
TI  - Intracavity coherent addition of single high-order modes.
AB  - We report on efficient intracavity coherent addition of several single high-order
      mode distributions in a multichannel laser resonator. The phase locking and
      coherent addition is achieved by using an intracavity interferometric beam
      combiner. The principle, configuration, and experimental results with pulsed
      Nd:YAG Laguerre-Gaussian TEM01 and TEM02 laser beam distributions are presented.
      The results reveal more than 95% combining efficiency with a nearly pure high
      order mode output beam distribution in both free-running and Q-switched
      operation.

PMID- 16092341
TI  - Visible and near-infrared responsivity of femtosecond-laser microstructured
      silicon photodiodes.
AB  - We investigated the current-voltage characteristics and responsivity of
      photodiodes fabricated with silicon that was microstructured by use of
      femtosecond-laser pulses in a sulfur-containing atmosphere. The photodiodes that
      we fabricated have a broad spectral response ranging from the visible to the near
      infrared (400-1600 nm). The responsivity depends on substrate doping,
      microstructuring fluence, and annealing temperature. We obtained room-temperature
      responsivities as high as 100 A/W at 1064 nm, 2 orders of magnitude higher than
      for standard silicon photodiodes. For wavelengths below the bandgap we obtained
      responsivities as high as 50 mA/W at 1330 nm and 35 mA/W at 1550 nm.

PMID- 16092342
TI  - Regenerative 40 Gbit/s wavelength converter based on similariton generation.
AB  - We present an all-optical regeneration technique based on spectral filtering of
      self-similar parabolic pulses (similaritons). In particular, we demonstrate
      numerically and experimentally that ghost pulses, which occur in the zero bit
      slots of telecommunication pulse trains, can be effectively suppressed. These
      results are obtained with a 40 Gbit/s pulse train.

PMID- 16092343
TI  - Bending-insensitive single-mode hole-assisted fibers with reduced splice loss.
AB  - We propose and demonstrate a novel type of bending-insensitive single-mode hole
      assisted fiber that has a doped core and two layers of holes with two different
      airhole diameters. The fiber has a 9.3 microm mode field diameter, a bending loss
      of 0.011 dB/turn at 1.55 microm for a bending diameter of 10 mm, and a cutoff
      wavelength below 1.1 microm. The fiber can be fusion spliced to a conventional
      single-mode fiber with low loss.

PMID- 16092344
TI  - Long optically controlled delays in optical fibers.
AB  - Optically controlled delay lines in optical fibers are demonstrated by use of the
      group-velocity control of signal pulses based on stimulated Brillouin scattering.
      We achieve continuous time delay within the range of 150 ns, much larger than the
      width of the 40 ns signal pulse, using cascaded fiber segments joined by
      unidirectional optical attenuators. In the meantime, we also observe a large
      amount of pulse broadening, which agrees well with a theoretical prediction based
      on linear theory.

PMID- 16092345
TI  - Strain and temperature characterization of photonic crystal fiber Bragg gratings.
AB  - A Bragg grating in a photonic crystal fiber was written and its dependence with
      temperature and strain analyzed. The two observed Bragg wavelengths correspond to
      a fundamental and a higher-order mode in the optical fiber. The temperature and
      strain calibration curves for both modes are measured and found to be distinct.
      The general properties of gratings in these fibers, and their implications, are
      enunciated.

PMID- 16092346
TI  - Resonance-temperature-insensitive phase-shifted long-period fiber gratings
      induced by surface deformation with anomalous strain characteristics.
AB  - Received February 18, 2005 We report the fabrication of phase-shifted long-period
      fiber gratings by use of a CO2 laser with a surface deformation technique and a
      point-by-point method. Due to periodicities that are structurally induced by a
      heat source and refractive-index modulation caused by a perturbational
      photoelastic effect, the results of thermal testing show a grating temperature
      coefficient of 28 pm/ degrees C at a range from 22 to 180 degrees C, indicating
      that the band rejections of the grating that is formed remain unchanged in their
      resonant strengths even at temperatures up to the fictive point of fiberglass. It
      is found for what is believed to be the first time that such a grating possesses
      an anomalous strain behavior of resonance with -1.52 x 10(-4) dB/muepsilon for
      the right notch and 7.05 x 10(-5) dB/muepsilon for the left notch.

PMID- 16092348
TI  - Three-dimensional imaging using spectral encoding heterodyne interferometry.
AB  - We present a novel heterodyne approach for performing fast, three-dimensional
      spectrally encoded imaging. Volumetric data of a volunteer's finger and of coin
      surfaces were acquired at a rate of 5 volume sets per second with a depth
      resolution of 145 microm.

PMID- 16092347
TI  - Interstitial Doppler optical coherence tomography.
AB  - Doppler optical coherence tomography (OCT) can image tissue structure and blood
      flow at micrometer-scale resolution but has limited imaging depth. We report a
      novel, linear-scanning, needle-based Doppler OCT system using angle-polished
      gradient-index or ball-lensed fibers. A prototype system with a 19-guage
      (diameter of approximately 0.9 mm) echogenic needle is constructed and
      demonstrates in vivo imaging of bidirectional blood flow in rat leg and abdominal
      cavity. To our knowledge, this is the first demonstration of Doppler OCT through
      a needle probe in interstitial applications to visualize deeply situated
      microcirculation.

PMID- 16092349
TI  - Optical levitation and manipulation of stuck particles with pulsed optical
      tweezers.
AB  - We report on optical levitation and manipulation of microscopic particles that
      are stuck on a glass surface with pulsed optical tweezers. An infrared pulse
      laser at 1.06 microm was used to generate a large gradient force (up to 10(-9) N)
      within a short duration (approximately 45 micros) that overcomes the adhesive
      interaction between the particles and the glass surface. Then a low-power
      continuous-wave diode laser at 785 nm was used to capture and manipulate the
      levitated particle. We have demonstrated that both stuck dielectric and
      biological micrometer-sized particles, including polystyrene beads, yeast cells,
      and Bacillus cereus bacteria, can be levitated and manipulated with this
      technique. We measured the single-pulse levitation efficiency for 2.0 microm
      polystyrene beads as a function of the pulse energy and of the axial displacement
      from the stuck particle to the pulsed laser focus, which was as high as 88%.

PMID- 16092350
TI  - Raman sorting and identification of single living micro-organisms with optical
      tweezers.
AB  - We report on a novel technique for sorting and identification of single
      biological cells and food-borne bacteria based on laser tweezers and Raman
      spectroscopy (LTRS). With this technique, biological cells of different
      physiological states in a sample chamber were identified by their Raman spectral
      signatures and then they were selectively manipulated into a clean collection
      chamber with optical tweezers through a microchannel. As an example, we sorted
      the live and dead yeast cells into the collection chamber and validated this with
      a standard staining technique. We also demonstrated that bacteria existing in
      spoiled foods could be discriminated from a variety of food particles based on
      their characteristic Raman spectra and then isolated with laser manipulation.
      This label-free LTRS sorting technique may find broad applications in
      microbiology and rapid examination of food-borne diseases.

PMID- 16092351
TI  - Fiber-optic-bundle-based optical coherence tomography.
AB  - A fiber-optic-bundle-based optical coherence tomography (OCT) probe method is
      presented. The experimental results demonstrate this multimode optical fiber
      bundle-based OCT system can achieve a lateral resolution of 12 microm and an
      axial resolution of 10 microm with a superluminescent diode source. This novel
      OCT imaging approach eliminates any moving parts in the probe and has a primary
      advantage for use in extremely compact and safe OCT endoscopes for imaging
      internal organs and great potential to be combined with confocal endoscopic
      microscopy.

PMID- 16092352
TI  - Polarimetric laser radar target classification.
AB  - Imaging laser radar (ladar) systems have been developed for automatic target
      identification in surveillance systems. Ladar uses the range value at the target
      pixels to estimate the target's 3-D shape and identify the target. For targets in
      clutter and partially hidden targets, there are ambiguities in determining which
      pixels are on target that lead to uncertainties in determining the target's 3-D
      shape. An improvement is to use the polarization components of the reflected
      light. We describe the operation and preliminary evaluation of a polarization
      diverse imaging ladar system. Using a combination of intensity, range, and degree
      of polarization, we are better able to identify and distinguish the target from
      other objects of the same class.

PMID- 16092353
TI  - Reconstruction method for weak-phase optical interferometry.
AB  - Current optical interferometers are affected by unknown turbulent phases on each
      telescope. We account for this lack of phase information by introducing system
      aberration parameters, and we solve the image reconstruction problem by
      minimizing an original joint criterion in the aberrations and in the object. We
      validate this method by means of simulations. Tests on experimental data are
      under way.

PMID- 16092354
TI  - Relaxation mechanisms in three-dimensional metamaterial lens focusing.
AB  - We study the transient behaviors in focusing a point source with a metamaterial
      lens (epsilon = mu = -1 + delta). We find the time evolutions of image formation
      are dictated by two relaxation mechanisms, namely, surface wave transport and
      absorption, determined, respectively, by Re(delta) and Im(delta). We show that
      image oscillations are inevitable in this three-dimensional configuration when
      Re(delta) double dagger 0 and establish relationships among the relaxation time,
      the resolution enhancement, and delta.

PMID- 16092355
TI  - Simple and compact 1-Hz laser system via an improved mounting configuration of a
      reference cavity.
AB  - We report an improved mounting configuration for a passive optical cavity used
      for laser frequency stabilization. The associated reduction of the vibration
      sensitivity of the effective cavity length has led to a simple and compact
      reference cavity system for laser stabilization at the level of 1 Hz linewidth.

PMID- 16092356
TI  - Upconversion multichannel infrared spectrometer.
AB  - A multichannel IR spectrometer using a standard silicon CCD array is
      demonstrated. Sum frequency generation between an ultrafast optical pulse and a
      frequency-dispersed IR beam generates a spatially extended optical signal that is
      collected on a generic CCD video camera. This method provides an inexpensive and
      efficient alternative to conventional multichannel IR arrays.

PMID- 16092357
TI  - Measurement of pulse amplitude and phase using cross-phase modulation in
      microstructure fiber.
AB  - Cross-phase modulation in a highly nonlinear microstructure optical fiber with
      low dispersion and high birefringence is used for the measurement of the pulse
      amplitude and phase of picosecond pulses by frequency-resolved optical gating. An
      alignment-free configuration including an optical amplifier is proposed and
      experimentally tested. The simulated annealing method is used for retrieving the
      amplitude and phase from cross-phase modulation spectrograms. It takes into
      account the birefringence of the measurement fiber and the resolution of the
      optical spectrum analyzer.

PMID- 16092358
TI  - Wavelength-dispersive device based on a Fourier-transform Michelson-type arrayed
      waveguide grating.
AB  - We propose a new type of arrayed waveguide grating (AWG) device that operates as
      a Fourier-transform (FT) spectrometer without the need of scanning elements. The
      large input aperture size typical of a FT spectrometer eliminates the requirement
      for a narrow single-mode input waveguide while still achieving high spectral
      resolution with a markedly increased light-gathering capability (etendue). An
      example of the device with a resolution of 0.07 nm (approximately 10 GHz) and
      designed for a silicon-on-insulator platform is presented. The calculated spectra
      show no noticeable deterioration for aperture widths as large as 40 microm,
      yielding more than a 50-fold increase in aperture size compared with conventional
      AWG or echelle grating based devices at the equivalent resolution.

PMID- 16092359
TI  - Comment on "microstructured polymer fiber laser".
AB  - We comment on the recent Letter by Argyros et al. [Opt. Lett. 29, 1882 (2004)] in
      which a microstructured polymer fiber doped with the dye Rhodamine 6G was
      discussed as a possible fiber laser source. We suggest that the lasing action at
      632 nm was due to stimulated Raman scattering in the poly(methyl methacrylate)
      host material.

PMID- 16092360
TI  - Middle-infrared luminescence of praseodymium ions in silver halide crystals and
      fibers.
AB  - The luminescence of AgBr, AgCl, and AgClBr crystals and fibers doped with Pr3+
      ions was investigated in the middle-infrared spectral range. We measured the
      absorption, emission, and kinetic parameters over a broad temperature range.
      Strong luminescence in the spectral range 4-5.5 microm was observed for the first
      time to our knowledge in silver halide crystals and fibers at room temperature.
      No noticeable differences were observed between the crystals and the fibers. We
      calculated various optical parameters for Pr:AgBr and Pr:AgCl crystals, using the
      Judd-Ofelt approximation. Both the measured results and the calculated parameters
      indicate that these doped crystals and fibers would be good candidates for the
      fabrication of mid-IR solid-state lasers or fiber lasers.

PMID- 16092361
TI  - Suppression of phase and supermode noise in a harmonic mode-locked erbium-doped
      fiber laser with a semiconductor-optical-amplifier-based high-pass filter.
AB  - By operating an intracavity semiconductor-optical-amplifier- (SOA-) based high
      pass filter at the nearly transparent current condition, the supermode noise
      (SMN), the relaxation oscillation, and the single-sideband (SSB) phase noise can
      be simultaneously suppressed in an actively mode-locked erbium-doped fiber laser
      (EDFL). The SOA at the nearly transparent condition enhances the SMN suppression
      ratio of the EDFL from 32 to 76 dB at the cost of the phase noise degrading from 
      114 to -104.2 dBc/Hz and broadening the pulse width from 36 to 61 ps. With an
      optical bandpass filter, the SSB phase noise and the SMN suppression ratio can be
      further improved to -110 dBc/Hz and 81 dB, respectively. The EDFL pulse can be
      further shortened to 3.1 ps with a time-bandwidth product of 0.63 after
      compression.

PMID- 16092362
TI  - Frequency and phase-lock control of a 3 THz quantum cascade laser.
AB  - We have locked the frequency of a 3 THz quantum cascade laser (QCL) to that of a
      far-infrared gas laser with a tunable microwave offset frequency. The locked QCL
      line shape is essentially Gaussian, with linewidths of 65 and 141 kHz at the -3
      and -10 dB levels, respectively. The lock condition can be maintained
      indefinitely, without requiring temperature or bias current regulation of the QCL
      other than that provided by the lock error signal. The result demonstrates that a
      terahertz QCL can be frequency controlled with 1-part-in-10(8) accuracy, which is
      a factor of 100 better than that needed for a local oscillator in a heterodyne
      receiver for atmospheric and astronomic spectroscopy.

PMID- 16092363
TI  - Observation of two-wave coupling during the formation of POLICRYPS diffraction
      gratings.
AB  - We report on the experimental observation of two-wave mixing that occurs inside a
      sample between the beams used for the fabrication of polymer-liquid-crystal
      polymer slices (POLICRYPS) diffraction gratings. The effect depends on the phase
      shift between the curing interference pattern and the grating being cured. This
      shift can be mechanically induced by accidental vibrations of the experimental
      setup; thus a high setup stability is needed. We devised a mechanism that enables
      us to control setup vibrations in situ and used it to monitor the experiment.
      When the mechanically induced shift was significantly small, wave mixing was
      observed only if the initial intensities of the two curing beams were different
      from each other.

PMID- 16092364
TI  - 5 Hz, > 250 mJ optical parametric chirped-pulse amplifier at 1053 nm.
AB  - A 250 mJ, 5 Hz repetition rate optical parametric chirped-pulse amplifier with
      near-Fourier-transform-limited, 430 fs pulses and a beam that can be focused to
      near the diffraction limit is demonstrated. A pump laser with engineered spatial
      and temporal profiles allows an overall pump-to-signal conversion efficiency of
      34% to be achieved.

PMID- 16092365
TI  - Induced spatiotemporal modulation instability in a noninstantaneous self
      defocusing medium.
AB  - We demonstrate theoretically and experimentally that induced spatiotemporal
      modulation instability can exist in a self-defocusing medium if the nonlinearity
      is noninstantaneous. We predict the growth rate as a function of the spatial and
      temporal frequencies of the modulation and the response time of the nonlinearity
      and confirm it by our experiments.

PMID- 16092366
TI  - Soliton control and bloch-wave filtering in periodic photonic lattices.
AB  - We suggest a novel approach to soliton control and routing based on Bloch-wave
      filtering in periodic photonic structures. Taking a binary waveguide array as an
      example, we demonstrate that spatial solitons that belong to different spectral
      gaps can be selectively reflected from or transmitted through an engineered
      defect, which acts as a low- or high-pass filter for Bloch waves.

PMID- 16092367
TI  - Zero-n gap soliton.
AB  - Periodic structures consisting of alternating layers of positive-index and
      negative-index materials have a novel bandgap at the frequency at which the
      average refractive index is zero. We show that, in the presence of a Kerr
      nonlinearity, this zero-n gap can switch from low transmission to a perfectly
      transmitting state, forming a nonlinear resonance or gap soliton in the process.
      This zero-n gap soliton is omnidirectional, in contrast to the usual Bragg gap
      soliton of positive-index periodic structures.

PMID- 16092368
TI  - Near-infrared cavity-dumped femtosecond optical parametric oscillator.
AB  - We demonstrate a high-energy near-infrared cavity-dumped femtosecond optical
      parametric oscillator (OPO) based on periodically poled lithium niobate. The
      laser generates 90 nJ pulses at a repetition rate of up to 1 MHz when
      synchronously pumped by 800 mW output from a femtosecond Ti:sapphire laser. The
      laser is broadly tunable from 1.0 to 1.5 microm in the signal branch, with a
      pulse duration of < 60 fs at 1.2 microm. High intracavity power is achieved by
      running the laser in the regime of positive group-velocity dispersion.

PMID- 16092369
TI  - Nonlinear dual-core photonic crystal fiber couplers.
AB  - We study nonlinear modes of dual-core photonic crystal fiber couplers made of a
      material with the focusing Kerr nonlinearity. We find numerically the profiles of
      symmetric, antisymmetric, and asymmetric nonlinear modes and analyze all-optical
      switching generated by the instability of the symmetric mode. We also describe
      elliptic spatial solitons controlled by the waveguide boundaries.

PMID- 16092370
TI  - Generation of backward terahertz waves in GaSe crystals.
AB  - We have observed a backward-propagating terahertz wave by mixing two coherent
      infrared beams in two GaSe crystals. For the 47 mm long crystal, the output
      wavelength can be tuned in the wide range of 167.6 to 2060 microm (0.146 to 1.79
      THz), whereas the output peak power reaches 217 W. The corresponding power
      conversion efficiency is approximately 0.03%.

PMID- 16092371
TI  - High-performance optical retarders based on all-dielectric immersion
      nanogratings.
AB  - High-performance true zero-order optical retarders were realized based on all
      dielectric immersion nanogratings. All-dielectric nanolaminate materials,
      deposited by atomic layer deposition, were utilized to fill the trenches of the
      nanogratings to form immersion nanogratings. The refractive index of the
      nanolaminate material can be dialed and controlled precisely by controlling the
      ratio of the two compositions forming the nanolaminate material. This
      significantly improves the design and process windows for realizing precise
      optical retarders, particularly very-low-phase retarders. Three 100-mm-diameter
      very-low-phase retarders with highly precise and uniform phase retardance and
      very high transmittance were realized by use of the all-dielectric immersion
      grating design and an atomic layer deposition technique.

PMID- 16092372
TI  - Polarization-selective etching in femtosecond laser-assisted microfluidic channel
      fabrication in fused silica.
AB  - We fabricate microchannels in fused silica by femtosecond laser irradiation
      followed by etching in diluted hydrofluoric acid. We show a dramatic dependence
      of the etch rate on the laser polarization, spanning 2 orders of magnitude. We
      establish the existence of an energy-per-pulse threshold at which etching of the
      laser-modified zones becomes highly polarization selective. The enhanced
      selective etching is due to long-range, periodic, polarization-dependent
      nanostructures formed in the laser-modified material.

PMID- 16092373
TI  - Near-field diffractive elements.
AB  - A novel near-field imaging system is proposed and simulated. It is seen that a
      significant improvement in performance in the presence of noise is possible
      without loss of resolution.

PMID- 16092374
TI  - Planar heterogeneous structures for coherent emission of radiation.
AB  - The coupling of excited surface polaritons with thermal radiation through
      diffraction by gratings results in coherent thermal emission in a certain
      frequency range toward well-defined directions for p polarization. A planar
      coherent source is proposed that uses multilayers of negative permittivity
      (epsilon) and negative permeability (mu) materials. Owing to the excitation of
      surface polaritons at the interface between the negative-epsilon and negative-mu
      layers, coherent emission can be achieved for both s and p polarization.
      Moreover, one can control the emission frequency and direction by adjusting the
      layer thicknesses.

PMID- 16092375
TI  - Quantum interference in atomic vapor observed by four-wave mixing with incoherent
      light.
AB  - Pairs of pulses from an incoherent source are used to investigate the time
      resolved four-wave mixing response of atomic rubidium when a two-photon resonance
      is involved in the nonlinear process. By varying the relative polarization of the
      pulse pairs, we are able to select the quantum pathways and clearly distinguish
      optical and quantum interferences.

PMID- 16092376
TI  - Geometrical form factor determination with Raman backscattering signals.
AB  - A new method is presented to determine the geometrical form factor in Raman
      lidar. Mie and Raman backscattering signals are acquired by L625 Raman lidar;
      then the aerosol backscattering ratio and atmospheric molecular density are
      derived. By normalizing the molecular density of Raman lidar with radiosonde
      measurements, the geometrical form factors of lidar are obtained. Experimental
      results indicate this method is feasible.

PMID- 16092377
TI  - Cumulative plasmon field enhancement in finite metal particle chains.
AB  - The dramatic field enhancement at the extremity of finite chains of strongly
      coupled gold nanoparticles illuminated under total internal reflection is
      investigated numerically. We demonstrate that high enhancement factors can be
      achieved by exploiting the in-plane forward scattering of the particles, with
      geometries achievable by state-of-the-art lithographic techniques.

PMID- 16092378
TI  - Colloidal subwavelength nanostructures for antireflection optical coatings.
AB  - A two-dimensional (2D) subwavelength nanostructure for antireflection coating is
      fabricated upon a transparent substrate. Self-assembled 2D colloidal crystals are
      used as a nanoscale composite material with controlled thickness and low
      refractive index. The feature size of the structure is approximately 105 nm. The
      structure is used for antireflection coating, and the measured reflectivity of a
      glass substrate is reduced to 0.3%. Enhanced transmission through the substrate
      is also observed.

PMID- 16092379
TI  - Femtosecond fiber lasers with pulse energies above 10 nJ.
AB  - A series of experiments aimed at determining the maximum pulse energy that can be
      produced by a femtosecond fiber laser is reported. Exploiting modes of pulse
      propagation that avoid wave breaking in a Yb fiber laser allows pulse energies up
      to 14 nJ to be achieved. The pulses can be dechirped to sub-100-fs duration to
      produce peak powers that reach 100 kW. The limitations to the maximum pulse
      energy are discussed.

PMID- 16092380
TI  - High-peak-power pulses from a cavity-dumped Yb:KY(WO4)2 oscillator.
AB  - We report generation of 1.35 microJ femtosecond laser pulses with a peak power of
      3 MW at 1 MHz repetition rate from a diode-pumped Yb:KY(WO4)2 laser oscillator
      with cavity dumping. By extracavity compression with a large-mode-area fiber and
      a prism sequence, we generate ultrashort pulses with a duration of 21 fs and a
      peak power of 13 MW.

PMID- 16092381
TI  - Bioethical consensus and the force of good ideas.

PMID- 16092382
TI  - Nutrition and hydration.

PMID- 16092383
TI  - Nutrition and hydration.

PMID- 16092384
TI  - Nutrition and hydration.

PMID- 16092385
TI  - Organs on the Internet.

PMID- 16092386
TI  - Wartime medical ethics.

PMID- 16092387
TI  - Wartime medical ethics.

PMID- 16092388
TI  - Wartime medical ethics.

PMID- 16092389
TI  - Britain's HFEA is caught in the middle.

PMID- 16092390
TI  - Ethics class.

PMID- 16092391
TI  - A new era in drug regulation?

PMID- 16092392
TI  - "Who lost China?" A foreshadowing of today's ideological disputes in bioethics.

PMID- 16092393
TI  - Organ solicitation on the Internet: every man for himself?

PMID- 16092394
TI  - Erring on the side of Theresa Schiavo: reflections of the special guardian ad
      litem.

PMID- 16092395
TI  - Schiavo's legacy: the need for an objective standard.

PMID- 16092396
TI  - The Schiavo case: a medical perspective.

PMID- 16092397
TI  - Hard cases and the politics of righteousness.

PMID- 16092398
TI  - Fallout from the pharma scandals: the loss of doctors' credibility?

PMID- 16092399
TI  - Singleton's story: choosing between psychosis and execution.

PMID- 16092400
TI  - Authenticity and ambivalence: toward understanding the enhancement debate.
AB  - The differences between critics and proponents of enhancement technologies are
      easily overblown. Both sides of this debate share the moral ideal of being
      "authentic" to oneself. They differ in how they prefer to understand
      authenticity, but even this difference is not as stark as it sometimes seems.

PMID- 16092402
TI  - Euthanasia is out of control in The Netherlands.

PMID- 16092401
TI  - Not just for experts: the public debate about reprogenetics in Germany.
AB  - When reproductive and genetic technologies spurred an extended German policy
      debate, the issues at stake went beyond the technologies to include the very
      meaning of "ethics" and the respective roles of ethicists and of the public in
      thinking about ethical questions.

PMID- 16092403
TI  - [Spectrofluorometric analysis of propranolol and atenolol].
AB  - The optimal conditions for spectrofluorimetric determination of propranolol and
      atenolol in substance and pharmaceutical preparations were determined.
      Simultaneous comparison with spectrophotometric method was performed.

PMID- 16092404
TI  - [Spectrofluorometric analysis of select 1,4-benzodiazepine derivatives].
AB  - The optimal conditions for spectrofluorimetric determination of oxazepam and
      nitrazepam in substance and pharmaceutical preparations were determined.
      Simultaneous comparison with spectrophotometric method was performed.

PMID- 16092405
TI  - [Naphthalenesulfonate compounds of alkylaminoalkyl drugs].
AB  - New compounds of alkylaminoalkyl with some naphthalenosulphonate (Na) were
      obtained and some of their physicochemical properties have been determined.
      Ability to formation of these compounds was utilised in qualitative and
      quantitative analysis of the above drugs.

PMID- 16092406
TI  - [Comparison of spectrophotometric and colorimetric methods in determination of
      clavulanic acid].
AB  - The spectrophotometric method for determination of clavulanic acid and
      amoxycillin after NaOH hydrolysis was elaborated.

PMID- 16092407
TI  - [Adsorption of tetracycline and oxytetracycline on Alusal].
AB  - The sorption of tetracycline and oxytetracycline on Alusal was studied. The
      proton complexes between tetracyclines and aluminium ions are formed.

PMID- 16092408
TI  - [Effect of antacids on pepsin activity in gastric acid].
AB  - The 9 widely used antacids were studied for antipepsic activity.

PMID- 16092409
TI  - [Study of allergen release from ointments and clinical evaluation of contact
      dermatitis. Effect of gentamicin sulfate].
AB  - The release of gentamycin sulfate from different ointment basis was studied.
      Contact hypersensitivity was determined in clinical studies.

PMID- 16092410
TI  - [Analysis of phenolic acids in cultured cells and in Penstemon Serrulatus Menz].
AB  - Qualitative and quantitative content of aromatic acids in callus tissues, cells
      in suspension cultures and intact plants of Penstemon serrulatus was determined
      by paper and gas chromatography. It has been observed that these acids occur in
      the investigated material mainly in bounded form. The largest quantities of
      phenolic acids were produced by callus tissues grown on Schenk and Hildebrandt's
      medium. The total content of aromatic acids found in the cells from suspension
      cultures was similar to the content of these compounds in intact plants, but
      twice lower than in callus tissue grown on the same medium.

PMID- 16092411
TI  - [Flavonoids in Arabis Caucasica Willd. (Cruciferae). Part I. Heterozygote similar
      to quercetin and isorhamnetin].
AB  - From flowering herb of Arabis caucasica Willd. have been isolated crystalline
      flavonoid compounds. They have been identified as quercetin 3-glucoside,
      isorhamnetin 3-glucoside, quercetin 3-beta-glucoside-7-alpha-rhamnoside and
      isorhamnetin 3-beta-glucoside-7-alpha-rhamnoside. As chromatographically
      homogenous, in amorphous form have been isolated: quercetin 3-diglucoside-7
      glucoside and isorhamnetin 3-diglucoside-7-glucoside.

PMID- 16092412
TI  - [New alkylated derivates and dissociation constans of 3-hydroxy-1,2
      benzisoxazole].
AB  - In the reactions of 3-hydroxy-1,2-benzisoxazole (BIO) and its 5-Cl and 6-Cl
      derivatives with ethyl bromoacetate were obtained the mixtures of O- and N-
      substituted esters but 7-NO2-BIO formed only O-ester. The products of N
      aminomethylation of 5-NO2-BIO were active against Trichomonas vaginalis. The
      structures of pure compounds have been confirmed by elementary analysis and IR
      spectrometry. Determinations of dissociation constants (pKa) of BIO, 5-Cl-BIO, 6
      Cl-BIO, 7-Cl-BIO, 5-F-BIO, 5-NO2-BIO, 7-NO2-BIO by potentiometric titration
      method were described. Investigated compounds have two values of ionisation
      constants except the nitro derivatives, this is the confirmation of equilibrium 3
      hydroxy-1,2-benzisoxazole <==> 1,2-benzisoxazolinone-3.

PMID- 16092413
TI  - [1-methyl-2-phenylpiperazine and 1-isopropyl-3-phenylpiperazine synthesis].
AB  - The synthesis of 1-methyl-2-phenylpiperazine and 1-isopropyl-3-phenylpiperazine
      as intermediates for potentially pharmacologically active compounds was
      described.

PMID- 16092414
TI  - [Synthesis of 1-N-aryloacetamidobutanol derivatives with anti-seizure effect].
AB  - New derivatives of 1-N-aryloacetamidobutanols were obtained in the reaction of
      arylalkylcarboxylic acid chlorides with R, S, R(-), S(+) 1-amino-2-butanols.
      Structures of the obtained compounds have been confirmed by elemental analysis
      and IR-spectrometry. Results of pharmacological studies will be published
      elsewhere.

PMID- 16092415
TI  - [1-amino-2-butanols derivates with antiarrhythmic effect].
AB  - R(-), R, S, S(+)-1-N-theophylline-7-acetyl or ethyl/-amino-2-butanols were
      obtained in the reaction of 7-methoxycarbonylmethyltheophylline or 7-beta
      chloroethyltheophylline with R(-), R, S, S(+) 1-amino-2-butanols. Compounds I and
      II tested for antiarrhythmic and hypotensive activity were inactive.

PMID- 16092416
TI  - [Derivates of carbodithiomethyl-carboxycrotonic acids and acetic acid anhydride].
AB  - N2-carbodithiomethyl-N1-3-carboxycrotonic acid hydrazide (I) was cyclized with
      acetic acid anhydride to (II). Unstable compound (II) was found to be converted
      by action dilute acids into compound (III). The obtained compound (III) was
      subjected to further reactions for preparing new compounds.

PMID- 16092417
TI  - [Study of the interaction of the compounds resulting from the reaction of
      carbodithiomethyl acid hydrazide with acetic acid. II].
AB  - N2-carbodithiomethyl-N1-3-carboxycrotonic acid hydrazide (I) was cyclized with
      acetic acid to (II) and concentrated sulphuric acid to (III). Unstable compound
      (II) was found to be converted by action concentrated sulphuric acid into
      compound (III). The obtained compound (III) was subjected to further reactions
      for preparing new compound.

PMID- 16092418
TI  - [Synthesis of radiosensitizing agents. Part V. Synthesis of 4-fluoro-3
      nitrophenacyl alkylxanthates].
AB  - Researching the potential radiosensitizers the paper describes several syntheses
      of 4-fluoro-3-nitrophenacyl alkylxanthates. The compounds are obtained as result
      of condensation 4-fluoro-3-nitrophenacyl bromide with respective potassium
      alkylxanthates where R are allyl-, ethyl-, propyl-, isopropyl-, butyl-, isobutyl
      , pentyl-, isopentyl-, hexyl-, heptyl-, octyl-, isooctyl-, decyl-, 3
      tetrahydrofurfuryl-, benzyl-, phenylethyl- and phenylpropyl-.

PMID- 16092419
TI  - [Synthesis of radiosensitizing agents. Part VI. Synthesis of 2,5-dichlorophenacyl
      alkylxanthates].
AB  - Researching the potential radiosensitizers the paper describes several syntheses
      of 2,5-dichlorophenacyl alkylxanthates. The compounds are obtained as result of
      condensation 2,5-dichlorophenacyl bromide with respective potassium
      alkylxanthates where R are: allyl-, ethyl-, propyl-, isopropyl-, butyl-, isobutyl
      , pentyl-, isopentyl-, hexyl-, heptyl-, octyl-, isooctyl-, decyl-, 3
      tetrahydrofurfuryl-, benzyl-, phenylethyl- and phenylpropyl-.

PMID- 16092420
TI  - [Synthesis and pharmacological properties of fluorostyryl derivatives of 3H
      pyrido[2,3]pyrimidine-4-one].
AB  - The synthesis of fluorostyryl derivatives of 3H-pyrido[2,3]pyrimidine-4-one was
      described.

PMID- 16092421
TI  - [2-merkaptobenzenosulfonamides derivates synthesis].
AB  - 1,3-Dialkyl-2-[2-mercapto-4-R(1)-5-(carboxy- or cyano)benzenesulphonyl]guanidines
      (Va-g, VI; R(1)=Cl or H) were synthesized by reactions of 3-methylthio-, 3
      mercapto- and 3-alkylamino-6-R(1)-7-(carboxy- or cyano)-1,4,2-benzoditiazine-1,1
      dioxides with amines. Their oxidation (VII) or methylation products (VIlIa-c, IXa
      c) as well novel 3-isobutylamino-6-chloro-7-R-1,4,2-benzodithiazine-1,1-dioxides
      (II, R=COCl; III, R=CONH2; IV, R=CN) which had been successfully used to the
      synthesis of compound VI, were also obtained.

PMID- 16092422
TI  - [Analysis of different ways of evaporation in Polish Pharmacopoeias].
AB  - Mechanism of evaporation of water from 13 pharmacopoeial organic hydrates using a
      thermogravimetric method was followed. Evaporation of water was analysed under
      the conditions described in the Polish Pharmacopeia IV. The results were compared
      with those obtained when dehydration was performed according to the other
      pharmacopeias.

PMID- 16092423
TI  - [Study of hydrogels containing amphotensides].
AB  - Hydrogels containing different amounts of amphotensides--carboxybetaine and
      amineoxide--have been obtained. It has been stated that obtained preparations in
      "in vitro" tests showed higher activity than commercially available ones, and
      their rheological properties--which can be modified in large range--permit to
      apply them topically with ease.

PMID- 16092424
TI  - IUPAC recommendation on nomenclature and symbols. Clinical Chemistry Division.
      Commision on Toxicology. Glossary of terms used in toxicology synopsis.

PMID- 16092425
TI  - Spectrophotometric determination of ketotifen in pharmaceutical preparations
      after isolation on ion-exchanger.
AB  - Spectrophotometric method have been proposed for the determination of ketotifen
      in complex "Position" (Polfa-Poznan) samples after preliminary separation of
      excipients. For the determinations of the ketotifen in Pozitan a relative
      standard deviation of +/-2.0% was found.

PMID- 16092426
TI  - High-performance liquid chromatographic determination of ethosuximide in plasma.
AB  - A HPLC method for a rapid determination of ethosuximide in plasma is described. A
      sample is extracted with ethyl ether from acidic medium with glutethimide as
      internal standard and injected onto analytical RP-18 column with
      spectrophotometric monitoring at 244 nm.

PMID- 16092427
TI  - Investigation of Fe(III) chloride as a colour reagent for the spectrophotometric
      determination of bumetanide in the pure form and in preparations.
AB  - The formation and stability of the complex between bumetanide (3-butylamino-4
      phenoxy-5-sulphamoylbenzoic acid) and Fe(III) ion was studied. It has been found
      that bumetanide reacts with Fe(III) chloride in the presence of ammonium
      thiocyanate at the pH 1.83-1.92 to form a violet complex soluble in chlorophorm,
      with the maximum absorbance at 514.5 nm. At the optimum experimental conditions
      the conditional stability constant of the complex was found to be log K' = 7.34.
      The Beer's law was obeyed up to the 160 microg x cm(-3) and the relative standard
      deviation varied from 0.406% to 0.475% (n = 10). The proposed method was found to
      be suitable for the accurate and sensitive analysis of bumetanide as a pure
      compound and from tables and ampoules.

PMID- 16092428
TI  - Spectrofluorimetric assay of azathioprine and 6-mercaptopurine in human blood
      plasma.
AB  - In this review is discussed a new modified assay measuring Azathioprine (AZA) and
      6-Mercaptopurine (6-MP) in human plasma using spectrofluorimetric method. After
      completed hydrolysis of AZA to 6-MP, the last has been oxidised to Purine-6
      sulphonate by two methods: using potassium chromate in the first method and
      potassium permanganate in the second one. Fluorescence of the solutions was
      measured at 393 nm with an excitation wavelength of 289 nm. Percentage of 6-MP
      remaining in toluene in the first method was 58 to 64. Comparing both methods of
      determination 6-MP it was noticed, that the first method is repeatable and can be
      applied for therapeutic drug monitoring.

PMID- 16092429
TI  - Application of arylosulfonic acids in analysis of antidepressive drugs.
AB  - Suitability of three phenylsulphonyloxybenzenesulfonic acids and their sodium
      salts to form new derivatives with antidepressive drugs were studied. Then
      physicochemical properties of the obtained arylosulfonates were tested. Reagents
      mentioned above were also used in analysis of these drugs.

PMID- 16092430
TI  - Bioavailability of indomethacin in liposomes.
AB  - The research concerned the influence of the liposomally-entrapped indomethacin on
      its absorption after intragastric administration to rats. It was found that the
      indomethacin entrapped in liposomes has a favorable influence on the
      bioavailability in comparison to sole indomethacin suspension.

PMID- 16092431
TI  - Polysaccharides from fruitbodies and mycelial culture of the fungus Trametes
      hirsuta (Wulf. ex Fr.) Lloyd.
AB  - The fruitbodies and mycelial culture of the wood destroying fungus Trametes
      hirsuta (Wulf. ex Fr.) Lloyd were investigated as a source of polysaccharides.
      Four different polysaccharide fractions were isolated from these sources with the
      good yield 4.76% (PfA) and 1.18% (PfB)--(fruitbodies) and 2.33% (PmcA), 3.25%
      (PmcB)--(mycelium) respectively. Some chemical differences were found in the
      composition of isolated polysaccharides. Some of them contained aminoacids as the
      structural components, especially those isolated from mycelial culture of the
      fungus. In all polysaccharide fractions glucose was present as a main monosugar.

PMID- 16092432
TI  - Biological activity of polysaccharides from the mycelial culture of Tylopilus
      felleus (Bull.: Fr.) P. Karst.
AB  - Polysaccharide A and B fractions from mycelial culture of Tylopilus felleus
      (Bull,: Fr.) P. Karst. were isolated. The acidic hydrolysis of the
      polysaccharides yielded glucose and peptidic part. Both polysaccharide fractions
      revealed mitodepressive and mitostatic activities in Allium test.

PMID- 16092433
TI  - Mitostatic and mitodepressive activities of polysaccharides from Saccharomyces
      cerevisiae Meyen T-411 strain and their preliminary chemical studies.
AB  - Hot water extracts of Saccharomyces cerevisiae Meyen T-411 strain provided the A
      and B polysaccharide fractions by alcohol precipitation. Both fractions revealed
      marked mitostatic and, or mitodepressive activities in Allium test. The fractions
      were purified with DEAE-Sephadex A-25 column what resulted in obtaining of the A1
      A5 and the B1-B5 subfractions. For the fractions and subfractions the elemental,
      sugar and amino acid analyses were carried out. Weight averaged molecular weights
      Mw of the A1 and B1 subfractions were estimated. Purified the A1-A5 and B1-B5
      subfractions were again evaluated in Allium test but their activities markedly
      declined.

PMID- 16092434
TI  - Pharmacological effects of Ukrain in rats and rabbits.
AB  - The effect of Ukrain administered in various doses on mean blood pressure (MAP)
      and breathing rate in rats and rabbits was evaluated. It was found that MAP was
      reduced and breathing rate increased significantly in both animal species.
      Maximum tolerated dose (MTD) of Ukrain was 10-fold higher in rats than in
      rabbits, and it amounted to 3.5 mg x kg(-1) and 0.35 mg x kg(-1), respectively.
      Possible clinical implications of these findings were discussed.

PMID- 16092435
TI  - Morphological evaluation of the effect of d-ribose on adriamycin-evoked
      cardiotoxicity in rats.
AB  - The influence of d-ribose on adriamycin-induced myocardiopathy in rats was
      studied. Adriamycin in the cumulative dose of 25 mg/kg evoked fully developed
      cardiac toxicity. D-ribose in the multiple doses of 200 mg/kg did not influence
      ADR cardiotoxicity.

PMID- 16092436
TI  - Pyrimidines as the cytostatic drugs.
AB  - Investigations on new cytostatic drugs have attracted a worldwide interest during
      the past few years. The pyrimidine derivatives possessing such the activity are
      amongst the biologically active compounds of a considerable pharmaceutical
      significance. All the research works on syntheses of these compounds are aimed at
      modifications in the cytosine ring or at changes in the dihydrofolic acid
      structure as well as at condensation of the pyrimidine ring system with other
      aromatic or heterocyclic rings.

PMID- 16092438
TI  - Pyrimidines as the potential circulatory drugs.
AB  - Chemical structures and biological activities of the novel, biologically active
      pyrimidine derivatives are being reviewed. The extensive pharmacological studies
      do indicate that some of these compounds may be regarded as very valuable
      circulatory drugs.

PMID- 16092437
TI  - Pyrimidines as the chemotherapeutic drugs.
AB  - Investigations on new chemotherapeutic drugs have attracted a worldwide interest
      during the past few years. The pyrimidine derivatives possessing such the
      activity have a considerable pharmaceutical significance. The works on these
      compounds are led in various directions, but a particular importance have
      modifications of the drug Trimetoprime as well as syntheses of new pipemidic acid
      derivatives and pyrimidines with the amide group.

PMID- 16092439
TI  - Studies on the products of conversion of 4-ethoxycarbonylmethyl-1,2,4-triazoline
      5-thione. VII. Synthesis of 4-beta-acetylaminoethyl derivatives of 1,2,4
      triazoline-5-thione.
AB  - In the reaction of 4-ethoxycarbonylmethyl-1,2,4-triazoline-5-thione derivatives
      (Ia,b) with the primary amines the corresponding amides (IIa,b-IVa,b) have been
      formed. These amides were then undergone to reduction with LiAlH4 leading to the
      formation of corresponding amines (Va,b-VIIa,b). Then by means of the reaction
      with acetic anhydride these amines were transformed into corresponding
      acetylamine derivatives of 1,2,4-triazoline-5-thione (VIIIa,b-Xa,b).

PMID- 16092440
TI  - Synthesis of new derivatives of thiosemicarbazide.
AB  - Reactions of methyl phthalimidodithiocarbamate with secondary amines were
      described. S-methyl and S-methylenecarboethoxy derivatives news compound were
      obtained. The reactions S-methyl derivatives with morpholine, piperidine and
      pyrrolidine were investigated.

PMID- 16092441
TI  - Synthesis of new derivatives of 4-hydroxy-(2H)-phthalazinone and phthalazino-1,4
      (2H)(3H)-dione.
AB  - N1-Phthaloyl-N3-substituted thiosemicarbazide (II-IV) in concentrated sulphuric
      acid were isomerized. New derivatives of 4-hydroxy-(2H)-phthalazinone and
      phthalazino-1,4-(2H)(3H)-dione were obtained.

PMID- 16092442
TI  - Derivatives of 2-mercaptobenzenesulphonamide. X. Synthesis of 1-dialkylaminoalkyl
      2-(2-mercaptobenzenesulphonyl)guanidines with potential pharmacological activity.
AB  - Synthesis of 2-(4-R(1)-5-R(2)-2-mercaptobenzenesulphonyl)derivatives of 1
      (dialkylaminoalkyl)-3-isobutylguanidine (III b-l) and 1,3-di(2
      dialkylaminoethyl)guanidine (IV-V) as well as subsequent S-2-aminoethylation
      reaction VI a-h, VII a-b have been described.

PMID- 16092443
TI  - Tensides from the group of propylene oxide and ethylene oxide copolymers. X.
      Solubilization of acetylsalicylic acid by polyetherodiol micelles.
AB  - The process of structural solubilization of acetylsalicylic acid in balanced
      systems (weight-balanced) by micelles of Rokopols of 30p160 and 30p60 types and,
      for comparison, by those of F-68 and F-108 Pluronics was investigated. The
      determined viscosity and hydrodynamic parameters allowed for the calculation of
      solubilizing activity of polyetherodiol micelles--n(s(A)). The results of the
      investigation point at Rokopols as an excipient, which may help to obtain new
      drug delivery systems.

PMID- 16092444
TI  - The history of the discovery and development of investigations on Tolpa's Peat
      Preparation (TPP).

PMID- 16092445
TI  - The technology of production of Tolpa peat preparation and its physical and
      chemical properties.

PMID- 16092446
TI  - Investigations on some pharmacological properties of TPP.
AB  - The experiments were performed on mice, rats and rabbits. The influence on
      circulatory, central nervous, and gastrointestinal system in vivo and in vitro,
      as well as on renal secretory activity was examined. TPP was administered p.o.,
      i.v. and s.c. at the doses 100.0-400.0 mg/kg. Either in a single dose or multiple
      doses TPP did not evoke any significant effects (as compared with NaCl solution)
      on blood pressure, heart and respiratory rate, general behaviour, locomotor
      activity, body temperature, locomotor coordination, ECoG, smooth muscles of
      intestine in vivo and in vitro, gastric secretion and on the volume and quality
      of excreted urine. The augmentation of sodium and potassium ion excretion with
      urine and slight influence on locomotor coordination both after TPP and 6% NaCl
      seems to be connected with a high content of salt in TPP.

PMID- 16092447
TI  - Tight junctions, leaky intestines, and pediatric diseases.
AB  - BACKGROUND: Tight junctions (TJs) represent the major barrier within the
      paracellular pathway between intestinal epithelial cells. Disruption of TJs leads
      to intestinal hyperpermeability (the so-called "leaky gut") and is implicated in
      the pathogenesis of several acute and chronic pediatric disease entities that are
      likely to have their origin during infancy. AIM: This review provides an overview
      of evidence for the role of TJ breakdown in diseases such as systemic
      inflammatory response syndrome (SIRS), inflammatory bowel disease, type 1
      diabetes, allergies, asthma, and autism. CONCLUSION: A better basic understanding
      of this structure might lead to prevention or treatment of these diseases using
      nutritional or other means.

PMID- 16092448
TI  - Clinical implications of mother-to-child transmission of HCV.
AB  - Testing for vertical transmission of hepatitis C virus (HCV) infection in infants
      and children will enable early identification of the majority of uninfected HCV
      exposed infants and children, and will provide significant emotional relief for
      the parents. CONCLUSION: The small percentage of infected children should be
      offered enrollment in well-designed clinical trials of optimal medical management
      for prevention of the predicted long-term outcomes of chronic HCV infection:
      chronic hepatitis, cirrhosis and hepatocellular carcinoma.

PMID- 16092449
TI  - Tackling childhood obesity: diet, physical activity or lifestyle change?
AB  - The present day, almost worldwide, fattening of children is widely attributed to
      both excessive energy intake and reduced physical activity. However, treatments
      which only focus on reducing energy intakes and increasing energy expenditures
      rarely show long-term success. The family attitudes and environments which
      contribute to energy imbalance and the development of obesity are virtually
      unchanged by many treatment programmes. We need to learn more about the nurture
      of those children who retain normal fatness although enveloped by obesity
      promoting environments. CONCLUSION: Better understanding of these children's
      lifestyles could lead to significant community-directed initiatives to promote
      normal childhood nutrition and growth even within affluent modem society.

PMID- 16092450
TI  - Interdisciplinary and prospective studies necessary to increase insight into
      developmental language disorders.
AB  - The study of developmental language disorders is discussed from an
      interdisciplinary perspective. It is argued that retrospective studies have
      provided valuable information on developmental language disorders that needs to
      be integrated into a theoretical model capable of capturing the basic mechanisms
      of language development. CONCLUSION: It is concluded that interdisciplinary and
      prospective studies and theoretical work are necessary to increase insight into
      developmental language disorders.

PMID- 16092451
TI  - Influence of smoking on metallothionein level and other proteins binding
      essential metals in human milk.
AB  - AIM: To assess the influence of smoking on the level of total protein,
      metallothionein (MT), albumin and lactoferrin in human breast milk. METHODS:
      Samples of whole milk and supernatants of milk after centrifugation at 10 000 x g
      and 105 000 x g were analysed. Cadmium was determined by graphite furnace atomic
      absorption spectrometry (GFAAS). The concentration measurements employed the
      following methods: total protein by Lowry, albumin by colorimetry, cotinine and
      lactoferrin by ELISA tests, metallothionein by 109Cd/haemoglobin assay. RESULTS:
      The assessment of tobacco smoke exposure was based on concentrations of cotinine
      in breast milk (197 +/- 98 ng/ml in smokers and 23 +/- 11 ng/ml in non-smokers; p
      < or = 0.001) and serum (179 +/- 87 ng/ml and 32 +/- 19 ng/ml, respectively; p <
      or = 0.001). The level of cadmium was four times higher in the milk of smoking
      women than in non-smokers. The concentration of total protein was lower in
      smoking (37.3 +/- 10.6 mg/ml) than in non-smoking mothers (51.8 +/- 13.8 mg/ml; p
      < or = 0.02). No significant differences between albumin and lactoferrin
      concentrations were observed. The level of metallothionein was over twice as low
      in smokers (5.1 +/- 1.9 microg/ml) than in non-smokers (13.4 +/- 3.0 microg/ml; p
      < or = 0.001), and an inverse correlation between MT level and cadmium
      concentration (r = -0.86; p = 0.001) was noticed. CONCLUSIONS: The breast milk of
      smoking mothers might be of lower nutritive value. The amount of MT transported
      by milk to the mammary gland is smaller in smokers than in non-smokers, which may
      prove to be advantageous to an infant because of the higher toxicity of the Cd-MT
      complex than that of inorganic Cd salts.

PMID- 16092452
TI  - Upper segment/lower segment ratio and armspan-height difference in healthy
      Turkish children.
AB  - AIM: The determination of body proportions is an important part of the clinical
      evaluation of children with short stature. The upper segment/lower segment ratio
      (US/LS ratio) and armspan-height difference is commonly used for this purpose.
      However, reference data are scarce in this respect, and available standards do
      not include standard deviations for the measurements. We aimed to establish the
      normal values for upper segment/lower segment ratio and armspan-height difference
      in Turkish children. METHODS: In the present study, height, upper and lower
      segment, and armspan were measured in 1302 healthy children (3-18 y). The age
      related mean and standard deviation curves of the US/LS ratio and armspan-height
      difference were constructed for each sex. RESULTS: The mean values of the US/LS
      ratio in boys were decreased from 1.108 at 3 y to 0.984 at 10 y. The nadir of the
      US/LS ratio (0.922) was reached at age 15 y. In girls, the mean value of the
      US/LS ratio gradually decreased to less than 1 at 9 y of age (1 y earlier than in
      boys). The nadir of the US/LS ratio (0.946) was reached at age 13 y in girls (2 y
      earlier than in boys). Armspan was shorter than height as expected in younger
      ages, but became slightly longer at around age 12 in girls and boys. Unlike boys,
      the armspan-height difference did not change much after puberty in girls.
      CONCLUSION: US/LS ratio and armspan-height difference are practical parameters
      and easy to perform in any setting. We hope that these standards will aid
      clinicians in the evaluation of children with short stature.

PMID- 16092453
TI  - Immunoglobulin heavy G2 chain (IGHG2) gene restriction in the development of
      severe respiratory syncytial virus infection.
AB  - AIM: Respiratory syncytial virus (RSV) is a prominent cause of airway morbidity
      in children under 1 y of age. It is assumed that host factors influence the
      severity of disease presentation, and thus the need for hospitalization. The
      variation of IGHG genes from chromosome 14q32 are linked to serum IgG subclass
      levels but also to the variations in IgG responses to pneumococcal, meningococcal
      and Haemophilus influenzae antigens. The aim of this investigation was to clarify
      whether IGHG genes are involved in the development of severe RSV lower
      respiratory tract infection (LRTI). METHODS: The alternative expressions of
      IGHG3(b) and (g), IGHG1(f) and (a), and IGHG2(n) and (-n) genes were studied in a
      cohort of 49 previously healthy children hospitalized for RSV LRTI. The gene
      frequencies were compared to a population of healthy individuals. RESULTS: The
      homozygous IGHG2(-n/-n) genotypes dominated in hospitalized children with severe
      RSV infection: 55.1%, compared with 34.2% in the healthy population (OR 2.3; p =
      0.004). The IGHG2 genotypes containing (n/n) and (n/-n) were significantly
      decreased. The IGHG(bf-n) alleles were significantly increased (OR 1.7; p =
      0.025) and the IGHG(bfn) alleles significantly decreased (OR 0.5; p = 0.005).
      CONCLUSION: The IGHG(bf-n) allele and homozygous IGHG2(-n/-n) genotypes are
      associated with the development of severe RSV LRTI.

PMID- 16092454
TI  - Bacterial aetiology of acute osteoarticular infections in children.
AB  - AIM: To study the bacterial aetiology of acute osteoarticular infections in
      children and to analyse the efficiency of culture methods. METHODS:
      Bacteriological data of 407 cases of clinically suspected osteoarticular
      infections affecting 406 children hospitalized in an orthopaedic surgery
      department between 1999 and 2002 were retrospectively reviewed. RESULTS:
      Bacterial cultures from clinical specimens were positive in 74 cases (18%): 38
      cases of septic arthritis and 36 cases of bone infections (osteitis,
      osteomyelitis or osteoarthritis). The use of liquid medium bottles to grow
      bacteria from articular fluids increased the rate of positive cultures compared
      to the use of standard solid media (p = 0.0001). The most commonly recovered
      pathogen was Staphylococcus aureus (44%) followed by Kingella kingae (14%),
      Streptococcus pyogenes (10%) and Streptococcus pneumoniae (10%). K. kingae was
      most frequently isolated among children under 36 mo of age (p = 0.0003), whereas
      S. aureus was most frequently isolated among children over 36 mo (p = 0.0015).
      CONCLUSION: By improving our culture method, we observed a recrudescence of
      isolation of K. kingae, but S. aureus remains the main pathogen isolated from
      osteoarticular infections in children. This finding is useful for the adaptation
      of a probabilistic antibiotic treatment of these infections.

PMID- 16092455
TI  - Accuracy of acute otitis media diagnosis in community and hospital settings.
AB  - AIM: To evaluate the accuracy rates of acute otitis media (AOM) diagnosis in the
      community by analyzing the initial AOM diagnosis (according to information from
      the referral letters to the Pediatric Emergency Department [PED]) among children
      with AOM diagnosis confirmed by tympanocentesis at PED. METHODS: A descriptive,
      retrospective study conducted during the year 2000, including 590 children aged 0
      48 mo diagnosed with AOM at PED. AOM was confirmed by tympanocentesis. We
      defined: (1) simple AOM as < 3 or < 4 episodes during the last 6 or 12 mo,
      respectively; (2) complicated AOM as > or = 3 or > or = 4 episodes during the
      last 6 or 12 mo, respectively, and/or not improving with antibiotics. RESULTS:
      571 (96.8%) were < 24 mo of age; 355 (60%) were Arab Bedouins and 235 (40%) Jews.
      Seventy-three pediatricians, 57 general practitioners and 27 family practitioners
      provided referral letters. Information on disease severity was available in
      471/590 (79.8%) patients, of whom 320 (68%) had simple and 151 (32%) complicated
      AOM. Three hundred and sixty-five (62%) of 590 patients were accurately diagnosed
      by referring physicians, more frequently in patients with complicated than simple
      AOM (p < 0.001). Diagnostic accuracy was similar among physician specialties (p =
      0.33) and ethnic groups (p = 0.11). Multivariable logistic regression analysis
      showed that complicated AOM, adjusted for age, sex, ethnic origin, and physician
      specialty, was the only predictive factor for accurate AOM diagnosis (odds ratio
      4.0, p < 0.001). CONCLUSIONS: Inaccurate diagnosis of AOM in community settings
      is common, occurring more frequently in simple than in complicated AOM, and is
      unrelated to physician specialty and children's ethnicity.

PMID- 16092456
TI  - Mortality among persons with a history of Kawasaki disease in Japan: can
      paediatricians safely discontinue follow-up of children with a history of the
      disease but without cardiac sequelae?
AB  - AIM: To clarify the question of whether patients with Kawasaki disease suffer a
      higher mortality rate after the incidence of the disease in comparison with age
      matched healthy individuals. METHODS: Between July 1982 and December 1992, 52
      collaborating hospitals collected data on all patients having a new, definite
      diagnosis of Kawasaki disease. Patients were followed up until 31 December 2001
      or their death. The expected number of deaths was calculated from Japanese vital
      statistics data and compared with the observed number. RESULTS: Of 6576 patients
      enrolled, 29 (20 males and 9 females) died. The standardized mortality ratio
      (SMR: the observed number of deaths divided by the expected number of deaths
      based on the vital statistics in Japan) was 1.15 (95% CI: 0.77-1.66). In spite of
      the high SMRs during the acute phase, the mortality rate was not high after the
      acute phase for the entire group of patients. Although the SMR after the acute
      phase was 0.75 for those without cardiac sequelae, six males (but none of the
      females) with cardiac sequelae died during this period; and the SMR for the male
      group with cardiac sequelae was 1.95 (95% CI: 0.71-4.25). The mortality from
      congenital anomalies of the circulatory system was elevated, but no increase in
      cancer deaths was observed. CONCLUSION: Although it was not statistically
      significant, the mortality rate among males with cardiac sequelae due to Kawasaki
      disease appeared to be higher than in the general population. On the other hand,
      the mortality rates for females with the sequelae and both males and females
      without sequelae were not elevated.

PMID- 16092457
TI  - Interferon gamma and tumour necrosis factor alpha in relation to anaemia and
      prognosis in childhood cancer.
AB  - This study examined whether the initial plasma levels of tumour necrosis factor
      alpha (TNFalpha) and interferon gamma (IFNgamma) in 131 children with newly
      diagnosed cancer were associated with haematopoietic suppression, and whether
      plasma levels of TNFalpha or haemoglobin at diagnosis affects long-term prognosis
      in childhood acute lymphoblastic leukaemia (ALL). CONCLUSIONS: IFNgamma, and
      possibly also TNFalpha, were related to anaemia in children with solid tumours.
      Neither TNFalpha levels nor Hb levels were associated with increased risk of ALL
      relapse.

PMID- 16092458
TI  - Survival after surgery for congenital heart defects: does reduced early mortality
      predict improved long-term survival?
AB  - AIM: The objectives of this study were 1) to compare early mortality (first 30 d
      after surgery) and long-term survival between two cohorts of patients operated on
      for congenital cardiac defects, and 2) to evaluate the impact of possible changes
      in early mortality on long-term survival. METHODS: 945 patients with congenital
      cardiac defects, born in 1990-1999 and operated on in the same period were
      examined in a retrospective cohort study. The patients were divided into three
      groups: "univentricular cardiac defects", "severe cardiac defects" and "less
      severe cardiac defects". The study population was divided into two cohorts: group
      1 included patients born and operated on in 1990-1994; group 2 included patients
      born and operated on in 1995-1999. The survival patterns in the two groups were
      compared. RESULTS: For all patients, except those with univentricular cardiac
      defects, early mortality (30 d after surgery) was reduced. Among patients with
      severe cardiac defects, early mortality was reduced from 18.6% in group 1 to 2.9%
      in group 2. Among patients with less severe cardiac defects, early mortality was
      reduced from 6.2% to 1.9%. The improved outcome was maintained during the
      following 5 y. Overall relative risk of death during follow-up was reduced to
      0.31 (95% CI: 0.15-0.56) for patients with severe cardiac defects, and to 0.53
      (95% CI: 0.31-0.93) for patients with less severe cardiac defects born and
      operated on in 1995-1999. CONCLUSION: Early mortality has been substantially
      reduced in congenital heart defect patients, and corresponds with significantly
      improved long-term survival.

PMID- 16092459
TI  - Excluding hepatitis C virus (HCV) infection by serology in young infants of HCV
      infected mothers.
AB  - AIM: To identify the age at which HCV infection can be accurately excluded by
      serology in young children born to HCV-infected mothers and to determine an
      appropriate schedule of antibody testing, most informative to clinical practice.
      METHODS: Children born to HCV-infected mothers were followed in centres of the
      European Paediatric HCV Network. Turnbull survival analysis techniques were used
      to estimate the age at which HCV-uninfected children will lose maternally
      acquired HCV antibodies. Factors associated with age at antibody loss were
      assessed in logistic regression. RESULTS: In 1104 children followed from birth
      and later confirmed to be HCV uninfected, an estimated 57% will have lost
      passively acquired HCV antibodies before 6 mo of age and an estimated 95% by 12
      mo. Maternal HCV viraemia antenatally was associated with later, and maternal HIV
      HCV co-infection with earlier loss of antibody. Actual antibody testing of
      uninfected children at 12 mo identified 82% of those tested to be anti-HCV
      negative. CONCLUSIONS: Serological confirmation of HCV uninfection remains
      necessary given the uncertainty in the specificity of virological tests. These
      results suggest that, in most children, HCV infection can be ruled out with
      serological testing at an earlier age than previously thought, and that nearly
      all children born to HCV-infected mothers will have lost passively acquired
      maternal antibodies by 1 y of age. Antibody loss was significantly later among
      children born to HCV viraemic mothers. The earlier loss of HCV antibodies in
      children born to HIV co-infected mothers may be due to HIV treatment.

PMID- 16092460
TI  - Trends in the epidemiology of neonatal sepsis of vertical transmission in the era
      of group B streptococcal prevention.
AB  - AIM: To assess trends in the epidemiology of culture-proven and clinical neonatal
      sepsis of vertical transmission in the era of intrapartum antibiotic prophylaxis.
      METHODS: Since 1995, the neonatal services of 28 acute-care teaching hospitals in
      Spain ("Grupo de Hospitales Castrillo") have been involved in the prospective
      surveillance of neonatal infection of vertical transmission. We here report the
      comparison of the incidence for the periods 1996-1997 and 2000-2001, and look
      separately at two groups of hospitals according to the time at which the official
      hospital policy to provide intrapartum antibiotic prophylaxis for group B
      Streptococcus (GBS) prevention was adopted. In 16 hospitals the policy was
      adopted in 1999 and in 10 before 1998 (nine hospitals in 1996, one in 1997).
      RESULTS: The incidence of proven sepsis decreased significantly by 22% and 54% in
      the hospitals that started prophylaxis in 1999 and before 1998, respectively. The
      incidence of GBS sepsis also declined significantly by 36.4% and 65.4% in both
      groups of hospitals, respectively. Significant variations in the incidence of
      clinical vertical sepsis as well as in the incidence of sepsis caused by
      Haemophilus influenzae and Klebsiella were not found. Sepsis caused by
      Escherichia coli increased in the hospitals with prophylaxis from 1999 and
      decreased in those that began prophylaxis before 1998, in which the mortality
      rate of proven and clinical sepsis also decreased significantly by 58.6%.
      CONCLUSIONS: There was a substantial decline in the incidence of proven vertical
      sepsis, with a significant reduction of GBS sepsis, although decreases were more
      marked when antibiotic prophylaxis was started before 1998. In this group of
      hospitals, there was also a decrease in the mortality rate. Fluctuations in the
      incidence of E. coli infection suggest the need for continuing epidemiological
      surveillance.

PMID- 16092461
TI  - The Milan Project: a newborn hearing screening programme.
AB  - AIM: Since 1997 a newborn hearing screening programme has been implemented by the
      U.O. Neurologia-Neurofisiopatologia and Dipartimento di Neonatologia of the
      Istituti Clinici di Perfezionamento ICP in Milan for both babies with no risk and
      those at risk of hearing impairment. This programme was named the Milan Project.
      METHODS: The protocol for no-risk babies consisted of three stages: in the first
      two stages, newborns were tested with transient click-evoked otoacoustic
      emissions (TEOAE), in the third one with conventional auditory brainstem
      responses (ABR). The first TEOAE test was performed by 36 h of age, before
      discharge, the second one after 15-30 d in case of referral, and the third one,
      by ABR, for those babies who failed the second TEOAE stage. Newborns at
      audiological risk were submitted to conventional ABR before the third month of
      corrected age. Some of this latter population was also submitted to the TEOAE
      test. The entire tested population (no-risk babies and newborns at audiological
      risk) consisted of 19 777 babies: 19 290 without risk ("no risk") and 487 at risk
      ("at risk"). RESULTS: During the course of the Milan Project, hearing impairment
      (ABR threshold equal to or greater than 40 dB nHL) was identified in 63 newborns
      (19 from the no-risk and 44 from the at-risk population), with a prevalence of
      0.32%. Bilateral hearing impairment (BHI) was found in 33 newborns (10 from the
      no-risk and 23 from the at-risk population), corresponding to 0.17%. Among
      infants with bilateral hearing impairment, 30.3% had no risk factors. The
      prevalence of hearing impairment was determined on days 15-30 after birth.
      CONCLUSIONS: The results show that the implementation of a hospital-based,
      universal neonatal hearing screening programme for babies with and without
      audiological risk is feasible and effective. The effectiveness of the programme
      has increased as a function of the years since its inception, with a strong
      decrease in the referral rate. Further improvement is obtained if the TEOAE
      measurements are repeated in cases of referral scoring before discharge.

PMID- 16092462
TI  - Role of physical activity and eating behaviour in weight control after treatment
      in severely obese children and adolescents.
AB  - AIM: To investigate the role of physical activity and eating behaviour in weight
      control 1.5 y after a weight-reduction programme in severely obese children.
      METHODS: Forty-seven children (13.4 +/- 2.1 y) were measured 1.5 y after the
      completion of a 10-mo residential treatment programme. Stature and body mass were
      measured; physical activity, fat and fibre intake, and self-efficacy in relation
      to physical activity and healthy eating behaviour were assessed using validated
      structured interviews. The total sample was divided into four subgroups according
      to unhealthy versus healthy physical activity and eating behaviour at follow-up.
      RESULTS: One-and-a-half years after treatment, subjects had regained 34 +/- 19%
      overweight, but were on average still 20 +/- 19% less overweight than before
      treatment (p < 0.001). The four subgroups did not differ in level of overweight
      at the beginning or end of treatment. At follow-up, there was a significant
      difference in overweight between the four subgroups (p < 0.05). The least healthy
      group (unhealthy physical activity and unhealthy eating behaviour) had a
      significantly higher level of overweight 1.5 y after treatment (183 +/- 36%) in
      comparison with the other groups (unhealthy physical activity and healthy eating:
      150 +/- 21%; healthy physical activity and unhealthy eating: 156 +/- 14%; healthy
      physical activity and healthy eating: 138 +/- 16%) (p < 0.05), whilst the
      healthiest group showed the lowest level of overweight after treatment when
      compared to the other groups (p < 0.05). CONCLUSION: Results suggest that both
      physical activity and nutritional habits play an important role in weight
      maintenance after initial weight loss in obese children and that one healthy
      behaviour can not compensate for another unhealthy behaviour.

PMID- 16092463
TI  - Comorbidity in severe developmental language disorders: neuropediatric and
      psychological considerations.
AB  - AIM: To explore possible patterns of comorbidity in children with severe
      developmental language disorders (DLD). METHODS: A retrospective investigation of
      the clinical records of 28 children relating to oral motor and language problems,
      psychological profiles, medical history and EEG findings. RESULTS: 36% of all the
      children had pure expressive language problems, 64% had combined expressive
      receptive language problems and 57% had additional oral motor problems. Girls
      predominated in expressive-receptive problems, while boys predominated in oral
      motor problems. Children with expressive-receptive disorders were over
      represented at the lower end of normal full-scale IQ (p = 0.015). Lower verbal
      than non-verbal IQ levels were almost as common as equal levels, but a lower non
      verbal IQ than verbal IQ was also found. Pre/perinatal problems were found in
      21%, and heredity for developmental language problems or dyslexia in 39%. There
      was a higher proportion of attention and motor problems, EEG abnormalities, and
      epileptic syndromes than in the general population (p < 0.001). CONCLUSION: In
      severe DLD, both pure expressive and mixed expressive-receptive problems are
      found, and oral motor problems are common. Gender differences regarding symptoms
      are present. Receptive language ability is associated with the full-scale IQ
      level. A high proportion of EEG abnormalities and epilepsy is found. There is a
      complex pattern of comorbidity between speech-language symptoms, psychological
      characteristics, heredity and EEG findings.

PMID- 16092464
TI  - Psychosocial adjustment in Swedish children with upper-limb reduction deficiency
      and a myoelectric prosthetic hand.
AB  - AIM: To study psychosocial adjustment and mental health in children with upper
      limb reduction deficiency and a myoelectric prosthetic hand. METHODS: Sixty-two
      parents of children aged 8 to 18 y old answered a questionnaire concerning
      competence and behaviour/emotional problems in their children. Of the 62
      children, 37 adolescents aged 11 to 18 y old answered questionnaires concerning
      competence, problems and mood state. The results were compared with Swedish
      normative data. The children were divided into five groups based on degree of
      myoelectric prosthetic use. RESULTS: Children with upper-limb reduction
      deficiency and a myoelectric prosthetic hand showed social competence and
      behaviour/emotional problems similar to Swedish standardized norms. However,
      withdrawn behaviour was significantly higher in all children, social competence
      was significantly lower in girls, and social activities were significantly lower
      in older children with upper-limb reduction deficiency. There was a significant
      difference between prosthetic use groups. Non-users had significantly more
      delinquent behaviour problems than full-time users. There was an interaction
      between gender and prosthetic use in their affect on competence and
      behaviour/emotional problems, yielding two contrasting patterns. CONCLUSION:
      Children with upper-limb reduction deficiency and a myoelectric prosthetic hand
      are as well adjusted psychosocially as their able-bodied peers. There are
      indications, however, of social stigmata related to the deficiency, which have to
      be considered differently in boys and girls.

PMID- 16092465
TI  - Test performance and self-esteem in relation to experienced stress in Swedish
      sixth and ninth graders--saliva cortisol levels and psychological reactions to
      demands.
AB  - AIMS: To study relations between test performance, academic self-esteem, self
      reported stress and saliva cortisol levels in students exposed to test demands at
      school. METHODS: 46 randomly selected 6th and 9th graders voluntarily
      participated in an experimental school test concerning reading and mathematics
      skills. Cortisol saliva samples were collected at awakening, 30 min later, before
      test and after test. Perceived stress was registered with a visual analogue scale
      (VAS). A standardized self-rating questionnaire for measuring self-esteem was
      administered together with questions about school stress and psychological
      reactions when exposed to stress during a test. RESULTS: Experienced stress
      during the school test was correlated to low test performance and to low self
      rated evaluation of self-esteem as well as to an increase of saliva cortisol
      levels during the test. There were also correlations between certain
      psychological reactions to demands and different cortisol measures. Children who
      reported that they applied the procedure "I say to myself: I can solve this task"
      in a school test situation had a lower morning increase of saliva cortisol.
      Reported use of the procedure "I get worried and will have problems solving other
      tasks too"--when referring to a school test situation--was correlated to an
      increase in cortisol levels during the test situation. CONCLUSION: Test
      performance, academic self-esteem, perceived stress and reactions of the
      hypothalamus-pituitary-adrenal axis (HPA axis) are highly intertwined.
      Furthermore, certain school stress psychological reactions to performance demands
      seem to be related to different cortisol reactions.

PMID- 16092466
TI  - Alarming prevalences of overweight and obesity for children of Turkish, Moroccan
      and Dutch origin in The Netherlands according to international standards.
AB  - AIM: Prevalences of overweight in The Netherlands, defined by international cut
      off points, are presented in 14 500 children of Dutch origin, 2904 of Turkish and
      2855 of Moroccan origin, aged 0-21 y. RESULTS: The mean prevalence for Turkish
      boys and girls was 23.4% and 30.2%, for Moroccans 15.8% and 24.5%, for Dutch
      youths in large cities 12.6% and 16.5%, and for other Dutch participants 8.7% and
      11.3%, respectively. CONCLUSION: The development of adequate prevention
      strategies is urgently needed.

PMID- 16092467
TI  - Anti-C(w) alloimmunization presenting as hydrops fetalis.
AB  - C(w) is a low frequency red cell antigen that belongs to the Rh blood groups
      system. While not uncommon, anti-C(w) is rarely associated with clinically
      significant haemolytic disease of the newborn (HDN). When it does occur, it is
      often subclinical or of mild to moderate clinical severity. In the majority of
      pregnancies it is considered to be a naturally occurring antibody and has not
      been reported to cause hydrops fetalis or stillbirth. We report a case of anti
      C(w) alloimmunization, which was associated with significant anaemia and hydrops
      fetalis, presenting at 35 wk gestation. CONCLUSION: Pregnancies affected by anti
      C(w) merit closer scrutiny. Consideration should be given to performing more
      frequent antenatal ultrasound assessments to detect hydrops fetalis. This may
      help to support the need for more invasive procedures (cordocentesis and
      intrauterine transfusions).

PMID- 16092468
TI  - Is orofacial granulomatosis in children a feature of Crohn's disease?
AB  - Orofacial granulomatosis is a term generally used to describe lip swelling
      secondary to an underlying granulomatous inflammatory process. Granulomatous
      cheilitis is the histopathological description of such inflammation occurring in
      the lips and surrounding tissues. Melkersson-Rosenthal syndrome (a triad of
      orofacial swelling, facial paralysis and a fissured tongue) is one manifestation
      of orofacial granulomatosis, which more commonly presents as granulomatous
      cheilitis alone. Oral Crohn's disease also belongs to the entity of orofacial
      granulomatosis. Most reported cases of orofacial granulomatosis have been in
      adults and some in adolescents. We present six children presenting with orofacial
      granulomatosis at an early age (range 5-8 y) whose course points towards the
      development of Crohn's disease. CONCLUSION: Orofacial granulomatosis in the
      paediatric population may be an initial manifestation of Crohn's disease and so
      careful surveillance is recommended.

PMID- 16092469
TI  - Giant congenital melanocytic naevus in association with hepatic melanin deposits.
AB  - This report describes a neonate with a giant congenital pigmented naevus over
      most of the trunk surface area, along with multiple satellite lesions, especially
      over the legs. Magnetic resonance imaging of the abdomen showed large deposits of
      melanin in the glutei bilaterally, the rectus abdominis muscles and the liver.
      Treatment consisted of repeated dermabrasion of the naevus over the lower back
      with CO2 laser (Silk Touch), followed by autologous skin grafting. No evidence of
      malignant transformation was observed. CONCLUSION: Giant congenital melanocytic
      naevus may be associated with involvement of internal organs other than the
      central nervous system.

PMID- 16092470
TI  - Reaching the limit of neonatal viability: how do we answer the question "how
      small is too small"?

PMID- 16092471
TI  - Pseudohyponatraemia and hyperviscosity due to IVIG therapy in a term newborn.

PMID- 16092472
TI  - Historic vote in Chicago. With NNOC, nurses vow renewed fight for patients.

PMID- 16092473
TI  - RNs win court fight, keep ratios.

PMID- 16092474
TI  - Surveys, studies overwhelmingly support staffing ratios.

PMID- 16092475
TI  - PASNAP targets mandatory overtime.

PMID- 16092477
TI  - Canada's Supreme Court invites privatization.

PMID- 16092478
TI  - A challenge to NHS. Britain's beloved institution takes hits from Labor.

PMID- 16092479
TI  - The 'right hand of the hospital' in a tumultuous land': 'Auxiliary nurses' in
      Chiapas.
AB  - For many, the road to a career in nursing is an unexpected one, with challenging
      twists and turns along the way. But rarely does it begin with escape down a rain
      beaten jungle path, pursued by wined soldiers and tanks. Such is the saga of
      group of young Mayan auxiliary nurses, who have steadfastly served their
      commuitities in the troubled southeastern Mexican state of Chiapas, a place where
      most doctors had fled.

PMID- 16092481
TI  - Tennessee dentists volunteering at home and around the world.

PMID- 16092480
TI  - It's called caregiving. In California, the social contract is being broken.

PMID- 16092482
TI  - Life is a highway.

PMID- 16092483
TI  - Keystone Dental Care, Inc.

PMID- 16092484
TI  - The history of the InterFaith Health Clinic.

PMID- 16092485
TI  - Free care the RAM way.

PMID- 16092486
TI  - Passion in action.

PMID- 16092487
TI  - I didn't want to go!

PMID- 16092490
TI  - Developmental disabilities dental clinic.

PMID- 16092489
TI  - Smile and see clinic.

PMID- 16092488
TI  - That didn't hurt at all.

PMID- 16092491
TI  - Area dentists participate in international missions.

PMID- 16092492
TI  - Good Samaritan Clinic.

PMID- 16092493
TI  - I found my niche.

PMID- 16092494
TI  - Labs want it all, and blood gas vendors oblige.

PMID- 16092496
TI  - Labs shaking hands with molecular middleman.

PMID- 16092497
TI  - Good tidings--the latest in chemistry analyzers.

PMID- 16092500
TI  - How to meet Medicare's teaching physician billing compliance rules.

PMID- 16092501
TI  - Antiretroviral drug studies in nonhuman primates: a valid animal model for
      innovative drug efficacy and pathogenesis experiments.
AB  - Several nonhuman primate models are used in HIV and AIDS research. In contrast to
      HIV-1 infection of chimpanzees, infection of macaque species with simian
      immunodeficiency virus (SIV) isolates results in a disease (simian AIDS) that
      shares many similarities with HIV infection and AIDS in humans. Although each
      animal model has its limitations and can never completely mimic HIV infection of
      humans, a carefully designed study allows experimental approaches, such as the
      control of certain variables, that are not feasible in humans, but that are often
      the most direct way to gain better insights in disease pathogenesis and provide
      proof-of-concept for novel intervention strategies. In the early days of the HIV
      pandemic, nonhuman primate models played a relatively minor role in the anti-HIV
      drug development process. During the past decade, however, the development of
      better virologic and immunologic assays, a better understanding of disease
      pathogenesis, and the availability of better drugs have made these animal models
      more practical for drug studies. In particular, nonhuman primate models have
      played an important role in demonstrating: (i) preclinical efficacy of novel
      drugs such as tenofovir; (ii) the benefits of chemoprophylaxis, early treatment
      and immunotherapeutic strategies; (iii) the virulence and clinical significance
      of drug-resistant viral mutants; and (iv) the role of antiviral immune responses
      during drug therapy. Comparison of results obtained in primate models with those
      observed in human studies will lead to further validation and improvement of
      these animal models. Accordingly, well-designed drug studies in nonhuman primates
      can continue to provide a solid scientific basis to advance our scientific
      knowledge and to guide future clinical trials.

PMID- 16092502
TI  - Intracellular trafficking of HIV-1 Gag: how Gag interacts with cell membranes and
      makes viral particles.
AB  - The Gag polyprotein of retroviruses and lentiviruses is the master orchestrator
      of viral particle formation. HIV-1 Gag is synthesized on cytosolic polysomes
      where it is co-translationally modified with the 14-carbon fatty acid myristate.
      New findings shed light on how myristoylated HIV-1 Gag traffics through the cell,
      binds to specific membranes, and assembles into virions. The affinity of Gag for
      membrane bilayers is regulated by a myristoyl switch; Gag multimerization induces
      the fatty acid to flip away from the protein, thereby promoting membrane binding
      during assembly. Several recent studies have shown that newly synthesized Gag
      traffics first to multivesicular bodies (MVB), endosomal compartments that
      contain protein complexes necessary for particle budding. Signals within Gag, as
      well as specific host-cell lipids and proteins, promote MVB localization. In
      macrophages, Gag is retained in MVBs; viral particles are formed within the MVB
      lumen and released from the cell via exocytosis. In other cell types, Gag and/or
      MVBs rapidly transit to the plasma membrane where particle release occurs. Given
      that MVB exocytosis is an essential host-cell pathway, effective antiviral agents
      will need to specifically target interaction of Gag with the endocytic pathway
      without perturbing the normal host-cell trafficking network.

PMID- 16092503
TI  - Mechanistic features of recombination in HIV.
AB  - The importance of recombination in retroviral evolution has been acknowledged for
      several decades. Consequently, after the identification of HIV as the etiological
      agent of AIDS, it was suspected that recombination could also play a central role
      in the evolution of this virus. However, only recently, extensive epidemiologic
      studies of HIV infections worldwide have provided an estimate for the occurrence
      of recombination in vivo, unveiling recombination frequencies that dwarf those
      initially expected. Nowadays, recombination is regarded as an integral part of
      the infectious cycle of this retrovirus, which impacts on diagnosis and treatment
      of infections, especially when genetically distant viruses have been at the
      origin of the recombinant forms. Retroviral recombination is observed when two
      genetically divergent genomic RNA molecules are present in the same viral
      particle, and arises during the reverse transcription step. This review focuses
      on the mechanisms that have been proposed to account for the occurrence of
      recombination in retroviruses, from the strand displacement model, according to
      which recombination occurs during second DNA strand synthesis; to the description
      of the factors responsible for copy-choice recombination during first DNA strand
      synthesis, such as the presence of breaks, pause sites, or secondary structures
      in the genomic RNA. Most of these models have been supported by experimental data
      obtained from in vitro reconstituted systems or from cell infection studies using
      academic model sequences. The situation in vivo is expected to be more complex,
      since several factors come into play when recombination involves relatively
      distant isolates, as in the case of inter-subtype recombination. At present, it
      is clear that further studies are needed in order to evaluate whether a
      prevailing mechanism exists for in vivo recombination, and these studies will
      also be essential for understanding how the underlying mechanisms of
      recombination contribute to the evolution of HIV.

PMID- 16092504
TI  - Pharmacogenetics in HIV therapy.
AB  - Administration of standard doses of most antiretroviral drugs results in
      significant variations in plasma drug concentrations among different individuals,
      as well as different rates of drug-associated toxicity. The reasons for the large
      interindividual variability in drug levels are multifactorial, and involve
      differences in gender metabolism, concomitant medications, drug compliance,
      underlying diseases, and genetic factors. Pharmacogenetics is the discipline that
      analyses the genetic basis for the interindividual variation in the body
      disposition of drugs. One of the main goals is to give grounds to individualized
      therapy. The majority of pharmacogenetic traits so far have involved drug
      metabolism. An example of this is the inherited variation in the pharmacokinetics
      and pharmacodynamics of drugs such as hydralazine or isoniazid. This variation is
      due to polymorphisms in the N-acetyltransferase-2 (NAT2) gene, which may split
      the population into three categories: slow, intermediate, and fast metabolizers.
      Pharmacogenetic studies conducted so far with antiretrovirals have focused on
      metabolizing enzymes and transporter proteins in the cell membrane. Herein, we
      review the genetic polymorphisms known to be associated with altered
      pharmacokinetics of antiretrovirals, which may influence the efficacy and
      toxicity of these drugs.

PMID- 16092505
TI  - Intracellular interactions between nucleos(t)ide inhibitors of HIV reverse
      transcriptase.
AB  - Current standard-of-care regimens recommended for the treatment of HIV infection
      include two or more nucleos(t)ide reverse transcriptase inhibitors (NRTI) in
      combination with a protease or non-nucleoside reverse transcriptase inhibitor.
      NRTIs are activated through interactions with the cellular machinery for
      regulating endogenous nucleoside triphosphate (NTP) pools. Once activated to
      their triphosphate form, NRTIs compete with natural 2'-deoxynucleoside
      triphosphates (dNTP) for incorporation by the virally encoded reverse
      transcriptase and host polymerases. Competitive inhibition, changes in enzyme
      expression, or allosteric modulation of cellular metabolizing enzymes may
      therefore alter NRTI activation or perturb cellular dNTP levels causing changes
      in NRTI antiviral activity and toxicity. This paper reviews the unique metabolic
      profiles of NRTIs and discusses methodologies for understanding the effects of
      combining them. Cell culture experiments assessing the antiviral synergy and
      intracellular metabolism of NRTI combinations have yielded valuable insights into
      the behavior of treatment regimens in vivo. The development of more reliable and
      convenient methods for detecting nucleotides, including those applying mass
      spectrometry, are helping to further elucidate the intracellular pharmacology of
      NRTIs. Studies assessing the potential for intracellular NRTI drug-drug
      interactions will facilitate a better understanding of the efficacy of current
      therapies, as well as the design of combination therapies with optimal activity
      and toxicity profiles.

PMID- 16092506
TI  - Canon law and health care ministry.

PMID- 16092507
TI  - Obstetrics and pediatrics: a medical view.

PMID- 16092508
TI  - Obstetrics and pediatrics: an ethical view.

PMID- 16092509
TI  - The theology of community benefit. Our tradition obliges us to reach out beyond
      our hospital walls.
AB  - The Catholic health ministry's concern for communities stems from the church's
      belief that human dignity is most fully expressed and recognized within the
      context of community. We humans are social beings by our very beings, and unless
      we involve ourselves in relationships with others, we fail to develop our innate
      human gifts. We who serve Catholic health care recognize that Jesus had a special
      affection for and ministry for the poor and vulnerable. Our church calls on us to
      provide service and advocacy for people whose disadvantages put them at society's
      margins. This obligation arises from the fact that all people--the healthy and
      the sick, the rich and the poor, the well-educated and the untaught--are children
      of the same loving God. Sharing that God, we are our "brother's keeper."

PMID- 16092510
TI  - Community benefit: what it is and isn't.
AB  - "Community benefit" is the measurable contribtution made by Catholic and other
      tax-exempt organizations to support the health needs of disadvantaged persons and
      to improve the overall health and well-being of local communities. Community
      benefit activities include outreach to low-income and other vulnerable persons;
      charity care for people unable to afford services; health education and illness
      prevention; special health care initiatives for at-risk school children; free or
      low-cost clinics; and efforts to improve and revitalize communities. These
      activities are often provided in collaboration with community members and other
      community organizations to improve local health and quality of life for everyone.
      Since 1989, the Catholic health ministry has utilized a systematic approach to
      plan, monitor, report, and evaluate the community benefit activities and services
      it provides to its communities. This approach, first described in CHA's Social
      Accountability Budget, was updated in the recent Community Benefit Reporting:
      Guidelines and Standard Definitions for the Community Benefit Inventory for
      Social Accountability. By using credible and consistent information, health care
      organizations can improve their strategic response to demands for information
      that demonstrates their worth.

PMID- 16092511
TI  - Does mission still matter? A hospital may forfeit its future by forgetting its
      community.
AB  - The public finds it increasingly difficult to distinguish voluntary, not-for
      profit health care organizations from their for-profit competitors. One result of
      this trend is challenges to not-for-profits' tax-exempt status. In 1987, this
      article's author, with Bruce Vladeck, published a book called Mission Matters: A
      Report on the Future of Voluntary Health Care Institutions. That book warned not
      for-profit hospitals that, if they were to survive, they must maintain a close
      relationship with their communities. They urged such hospitals to nurture five
      traditional characteristics: Values that reflect community commitment.
      Accountability to patients and communities. Long-term commitment in the face of
      short-term trends and opportunities. A physician-hospital relationship that
      fosters a symbiosis of service. Institutional voluntarism that allows
      institutions to be both provider and beneficiary of community service. In this
      article, the author seeks to remind leaders of voluntary, not-for-profit
      institutions, including Catholic institutions, that they neglect community
      service at their own peril.

PMID- 16092512
TI  - The community need index. A new tool pinpoints health care disparities in
      communities throughout the nation.
AB  - Catholic Healthcare West, San Francisco (CHW), has developed a national Community
      Need Index (CNI) in partnership with Solucient, an information products company,
      to help health care organizations, not-for-profits, and policymakers identify and
      address barriers to health care access in their communities. The CNI aggregates
      five socioeconomic indicators long known to contribute to health disparity-
      income, culture/language, education, housing status, and insurance coverage--and
      applies them to every zip code in the United States. Each zip code is then given
      a score ranging from 1.0 (low need) to 5.0 (high need). Residents of communities
      with the highest CNI scores were shown to be twice as likely to experience
      preventable hospitalization for manageable conditions--such as ear infections,
      pneumonia or congestive heart failure--as communities with the lowest CNI scores.
      The CNI provides compelling evidence for addressing socioeconomic barriers when
      considering health policy and local health planning. The tool highlights health
      care disparities between geographic regions and illustrates the acute needs of
      several notable geographies, including inner city and rural areas.Further, it
      should enable health care providers, policymakers, and others to allocate
      resources where they are most needed, using a standardized, quantitative tool.
      The CNI provides CHW with an important means to strategically allocate resources
      where it will be most effective in maintaining a healthy community.

PMID- 16092513
TI  - Seeing Community Benefit broadly. Everybody wins when hospitals collaborate with
      others to serve their communities.
AB  - Community benefit is an opportunity for hospitals and health systems to affirm
      their community-focused missions and to ensure implementation of those missions
      in their organizations. There are four key themes of community benefit: community
      health improvement, underserved populations and unmet needs, collaboration
      outside the hospital, and coordination and strategic management inside the
      hospital. Together, these constitute a broader perspective, one in which
      community benefit is of strategic value to both the community and the hospital,
      and serves as a departure point for some of the hospital's most fruitful
      contributions to health and well-being. The community benefit function can be
      organized and managed to achieve specific priorities with measurable objectives,
      just like any other hospital activity. There are innumerable examples of creative
      and successful models for community benefit programs that incorporate the
      principles of community health improvement, unmet needs, collaboration
      externally, and strategic management internally. These are models that hospital
      leaders should create and pursue, because they demonstrate the value of a broad
      view of community benefit that fully realizes the potential of hospitals'
      charitable purpose.

PMID- 16092514
TI  - Telling the community benefit story. We must remind our neighbors that we do much
      more than provide acute care.
AB  - The nation's not-for-profit voluntary hospitals--Catholic organizations among
      them--provide much more than acute, outpatient, and long-term care. They also
      provide a variety of services-including clinics for the uninsured, parish nurse
      programs, in-school programs for children--that reach out to people who are poor,
      vulnerable, and neglected. Unfortunately, this fact has not been communicated
      well. As a result, many people have a tendency to ask of these hospitals: "What
      have you done for me lately?" Voluntary hospitals should do more to communicate
      their community benefit activities to their various constituencies. Celebration
      should be the thrust--celebration of the hard work of physicians and staff and
      their dedication to the communities in which they live. If that fact is
      celebrated and communicated effectively, voluntary hospitals will find their
      communities celebrating with them.

PMID- 16092515
TI  - The Mercies surprise Baltimore. Community benefit, not profit, was the motive
      behind the preservation in 1887 of the city's downtown hospital.

PMID- 16092516
TI  - "Do good and talk about it". A CHRISTUS health study emphasizes the importance of
      telling our stories to the public.
AB  - In a time of public scrutiny, it is paramount that Catholic health care
      organizations examine their commitments to their communities and effectively
      communicate community benefit activities to stakeholders-employees, physicians,
      patients, and the public. CHRISTUS Academy, a leadership development program at
      CHRISTUS Health, Irving, TX, conducted two studies regarding community benefit.
      The first researched community benefit practices at more than 20 highly
      respected, tax-exempt CHA- and VHA-member organizations, comparing them with the
      practices of about 40 publicly traded, for-profit organizations. The primary
      conclusion was that community benefit is not just about measuring the numbers-it
      is also about "telling the story." Unlike the for-profit organizations, tax
      exempt health care organizations tend to struggle with adequately measuring and
      reporting their community contributions. In a second study, the academy surveyed
      CHRISTUS Health's employees and physicians regarding their knowledge of the
      system's commitment vis-a-vis identifying and meeting community needs. The vast
      majority said the system is important to the community and is actively involved
      in understanding and meeting the needs of the community. However, they also
      ranked the system lower in terms of working with other community organizations,
      being a leader in community health, and being known for sponsoring volunteer
      activities. These lower rankings indicate that the community benefit activities
      are not well publicized or known within the organization. Catholic health
      organizations must take an active approach in communicating their work to the
      public, the media, and each other. In doing so, they fulfill an integral part
      their mission.

PMID- 16092517
TI  - The hospital staff and community benefit. An Iowa facility works to involve busy
      employees in community benefit reporting.
AB  - Mercy Medical Center-North Iowa (MMC), Mason City, IA, has done much over the
      years to support the poor and underserved of its community. However, in recent
      years, the facilities leaders came to see that much of its community benefit
      activity went unreported. They decided to launch an initiative to improve this
      reporting. They began, in the summer of 2002, with a campaign to educate staff
      members about the facility's sponsor, the Sisters of Mercy, and that
      congregation's foundress, Mother Catherine McAuley. In December, MMC adopted a
      biannual reporting cycle for community benefit activities. Such reporting was
      facilitated by putting it online. More recently, MMC has begun publicizing its
      community benefit activities. As a result, both the facility's staff and the
      community have gained a clearer idea of the services that MMC provides in north
      Iowa.

PMID- 16092518
TI  - The challenge of resource allocation: wise decisions require organizations to ask
      difficult questions.

PMID- 16092519
TI  - A "branding program" puts El Proyecto on the map.

PMID- 16092520
TI  - Signal recognition particles in chloroplasts, bacteria, yeast and mammals
      (review).
AB  - The Signal Recognition Particle (SRP) plays a critical role in the sorting of
      nascent secretory and membrane proteins. Remarkably, this function has been
      conserved from bacteria, where SRP delivers proteins to the inner membrane,
      through to eukaryotes, where SRP is required for targeting of proteins to the
      endoplasmic reticulum. This review focuses on present understanding of SRP
      structure and function and the relationship between the two. Furthermore, the
      similarities and differences in the structure, function and cellular role of SRP
      in bacteria, chloroplasts, fungi and mammals will be stressed.

PMID- 16092521
TI  - Sec-dependent protein translocation across biological membranes: evolutionary
      conservation of an essential protein transport pathway (review).
AB  - All living organisms, no matter how simple or complex, possess the ability to
      translocate proteins across biological membranes and into different cellular
      compartments. Although a range of membrane transport processes exist, the major
      pathway used to translocate proteins across the bacterial cytoplasmic membrane or
      the eukaryotic endoplasmic reticulum membrane is conserved and is known as the
      Sec or Sec61 pathway, respectively. Over the past two decades the Sec and Sec61
      pathways have been studied extensively and are well characterised at the genetic
      and biochemical levels. However, it is only now with the recent structural
      determination of a number of the key elements of the pathways that the
      translocation complex is beginning to give up its secrets in exquisite molecular
      detail. This article will focus on the routes of Sec- and Sec61-dependent
      membrane targeting and the nature of the translocation channel in bacteria and
      eukaryotes.

PMID- 16092522
TI  - Type 1 protein secretion in bacteria, the ABC-transporter dependent pathway
      (review).
AB  - The relatively simple type 1 secretion system in gram-negative bacteria is
      nevertheless capable of transporting polypeptides of up to 800 kDa across the
      cell envelope in a few seconds. The translocator is composed of an ABC
      transporter, providing energy through ATP hydrolysis (and perhaps the initial
      channel across the inner membrane), linked to a multimeric Membrane Fusion
      Protein (MFP) spanning the initial part of the periplasm and forming a continuous
      channel to the surface with an outer membrane trimeric protein. Proteins targeted
      to the translocator carry an (uncleaved), poorly conserved secretion signal of
      approximately 50 residues. In E. coli the HlyA toxin interacts with both the MFP
      (HlyD) and the ABC protein HlyB, (a half transporter) triggering, via a
      conformational change in HlyD, recruitment of the third component, TolC, into the
      transenvelope complex. In vitro, HlyA, through its secretion signal, binds to the
      nucleotide binding domain (NBD or ABC-ATPase) of HlyB in a reaction reversible by
      ATP that may mimic initial movement of HlyA into the translocation channel. HlyA
      is then transported rapidly, apparently in an unfolded form, to the cell surface,
      where folding and release takes place. Whilst recent structural studies of TolC
      and MFP-like proteins are providing atomic detail of much of the transport path,
      structural analysis of the HlyB NBD and other ABC ATPases, have revealed details
      of the catalytic cycle within an NBD dimer and a glimpse of how the action of
      HlyB is coupled to the translocation of HlyA.

PMID- 16092523
TI  - Type III secretion: a secretory pathway serving both motility and virulence
      (review).
AB  - 'Type III secretion' (T3S) refers to a secretion pathway that is common to the
      flagellae of eubacteria and the injectisomes of some gram-negative bacteria.
      Flagellae are rotary nanomachines allowing motility but they contain a built-in
      secretion apparatus that exports their own distal components to the distal end of
      the growing structure where they polymerize. In some cases they have been shown
      to export non-flagellar proteins. Injectisomes are transkingdom communication
      apparatuses allowing bacteria docked at the surface of a eukaryotic cell membrane
      to inject effector proteins across the two bacterial membranes and the eukaryotic
      cell membrane. Both nanomachines share a similar basal body embedded in the two
      bacterial membranes, topped either by a hook and a filament or by a stiff short
      needle. Both appear to be assembled in the same fashion. They recognize their
      substrate by a loose N-terminal peptide signal and the help of individual
      chaperones of a new type.

PMID- 16092525
TI  - Protein secretion in the absence of ATP: the autotransporter, two-partner
      secretion and chaperone/usher pathways of gram-negative bacteria (review).
AB  - Bacteria secrete a wide variety of proteins, many of which play important roles
      in virulence. In gram-negative bacteria, these proteins must cross the
      cytoplasmic or inner membrane, periplasm, and outer membrane to reach the cell
      surface. Gram-negative bacteria have evolved multiple pathways to allow protein
      secretion across their complex envelope. ATP is not available in the periplasm
      and many of these secretion pathways encode components that harness energy
      available at the inner membrane to drive secretion across the outer membrane. In
      contrast, the autotransporter, two-partner secretion and chaperone/usher pathways
      are comparatively simple systems that allow secretion across the outer membrane
      without the need for input of energy from the inner membrane. This review will
      present overviews of these 'self-sufficient' pathways, focusing on recent
      advances and secretion mechanisms. Similarities among the pathways and with other
      protein translocation mechanisms will be highlighted.

PMID- 16092524
TI  - Structural and dynamic properties of bacterial type IV secretion systems
      (review).
AB  - The type IV secretion systems (T4SS) are widely distributed among the gram
      negative and -positive bacteria. These systems mediate the transfer of DNA and
      protein substrates across the cell envelope to bacterial or eukaryotic cells
      generally through a process requiring direct cell-to-cell contact. Bacteria have
      evolved T4SS for survival during establishment of pathogenic or symbiotic
      relationships with eukaryotic hosts. The Agrobacterium tumefaciens VirB/D4 T4SS
      and related conjugation machines serve as models for detailed mechanistic studies
      aimed at elucidating the nature of translocation signals, machine assembly
      pathways and architectures, and the dynamics of substrate translocation. The A.
      tumefaciens VirB/D4 T4SS are polar-localized organelles composed of a secretion
      channel and an extracellular T pilus. These T4SS are assembled from 11 or more
      subunits. whose membrane topologies, intersubunit contacts and, in some cases, 3
      dimensional structures are known. Recently, powerful in vivo assays have
      identified C-terminal translocation signals, defined for the first time the
      translocation route for a DNA substrate through a type IV secretion channel, and
      supplied evidence that ATP energy consumption contributes to a late stage of
      machine morphogenesis. Together, these recent findings describe the mechanics of
      type IV secretion in unprecedented detail.

PMID- 16092526
TI  - Evolution of the general protein import pathway of plastids (review).
AB  - The evolutionary process that transformed a cyanobacterial endosymbiont into
      contemporary plastids involved not only inheritance but also invention. Because
      gram-negative bacteria lack a system for polypeptide import, the envelope
      translocon complex of the general protein import pathway was the most important
      invention of organelle evolution resulting in a pathway to import back into
      plastids those nuclear-encoded proteins supplemented with a transit peptide.
      Genome information of cyanobacteria, phylogenetically diverse plastids, and the
      nuclei of the first red alga, a diatom, and Arabidopsis thaliana allows us to
      trace back the evolutionary origin of the twelve currently known translocon
      components and to partly deduce their assembly sequence. Development of the
      envelope translocon was initiated by recruitment of a cyanobacterial homolog of
      the protein-import channel Toc75, which belongs to a ubiquitous and essential
      family of Omp85/D15 outer membrane proteins of gram-negative bacteria that
      mediate biogenesis of beta-barrel proteins. Likewise, three other translocon
      subunits (Tic20, Tic22, and Tic55) and several stromal chaperones have been
      inherited from the ancestral cyanobacterium and modified to take over the novel
      function of precursor import. Most of the remaining subunits seem to be of
      eukaryotic origin, recruited from pre-existing nuclear genes. The next subunits
      that joined the evolving protein import complex likely were Toc34 and Tic110, as
      indicated by the presence of homologous genes in the red alga Cyanidioschyzon
      merolae, followed by the stromal processing peptidase, members of the Toc159
      receptor family, Toc64, Tic40, and finally some regulatory redox components
      (Tic62, Tic32), all of which were probably required to increase specificity and
      efficiency of precursor import.

PMID- 16092527
TI  - Protein import into mitochondria: origins and functions today (review).
AB  - Mitochondria are organelles derived from alpha-proteobacteria over the course of
      one to two billion years. Mitochondria from the major eukaryotic lineages display
      some variation in functions and coding capacity but sequence analysis
      demonstrates them to be derived from a single common ancestral endosymbiont. The
      loss of assorted functions, the transfer of genes to the nucleus, and the
      acquisition of various 'eukaryotic' proteins have resulted in an organelle that
      contains approximately 1000 different proteins, with most of these proteins
      imported into the organelle across one or two membranes. A single translocase in
      the outer membrane and two translocases in the inner membrane mediate protein
      import. Comparative sequence analysis and functional complementation experiments
      suggest some components of the import pathways to be directly derived from the
      eubacterial endosymbiont's own proteins, and some to have arisen 'de novo' at the
      earliest stages of 'mitochondrification' of the endosymbiont. A third class of
      components appears lineage-specific, suggesting they were incorporated into the
      process of protein import long after mitochondria was established as an organelle
      and after the divergence of the various eukaryotic lineages. Protein sorting
      pathways inherited from the endosymbiont have been co-opted and play roles in
      intraorganelle protein sorting after import. The import apparatus of animals and
      fungi show significant similarity to one another, but vary considerably to the
      plant apparatus. Increasing complexity in the eukaryotic lineage, i.e., from
      single celled to multi-cellular life forms, has been accompanied by an expansion
      in genes encoding each component, resulting in small gene families encoding many
      components. The functional differences in these gene families remain to be
      elucidated, but point to a mosaic import apparatus that can be regulated by a
      variety of signals.

PMID- 16092528
TI  - Oxa1/Alb3/YidC system for insertion of membrane proteins in mitochondria,
      chloroplasts and bacteria (review).
AB  - Recent studies have shown that there is a pathway that is evolutionarily
      conserved for the insertion of proteins into the membrane in mitochondria,
      chloroplasts, and bacteria. In this pathway, the Oxa1/Alb3/YidC proteins are
      believed to function as membrane insertases that play an important role in the
      membrane protein biogenesis of respiratory and energy transduction proteins.
      Additional roles of the Oxa1/Alb3/YidC members may be in the lateral integration
      of proteins into the lipid bilayer, and in the folding and assembly of proteins
      into membrane protein complexes.

PMID- 16092529
TI  - The Tat pathway in bacteria and chloroplasts (review).
AB  - Both in prokaryotic organisms and in chloroplasts, a specialized protein
      transport pathway exists which is capable of translocating proteins in a fully
      folded conformation. Transport is mediated in both instances by signal peptides
      harbouring a twin-arginine consensus motif (twin-arginine translocation (Tat)
      pathway). The Tat translocase comprises the three functionally different membrane
      proteins TatA, TatB, and TatC. While TatB and TatC are involved in the specific
      recognition of the substrate, TatA might be the major pore-forming component.
      Current evidence suggests that a functional Tat translocase is assembled from
      separate TatBC and TatA assemblies only on demand, i.e., in the presence of
      transport substrate and a transmembrane H+-motive force.

PMID- 16092530
TI  - Protein translocation into and within cyanelles (review).
AB  - The cyanelles of the glaucocystophyte alga Cyanophora paradoxa resemble
      endosymbiotic cyanobacteria in morphology, pigmentation and, especially, in the
      presence of a peptidoglycan wall situated between the inner and outer envelope
      membranes. However, it is now clear that cyanelles in fact are primitive
      plastids. Phylogenetic analyses of plastid, nuclear and mitochondrial genes
      support a single primary endosymbiotic event. In this scenario cyanelles and all
      other plastid types are derived from an ancestral photosynthetic organelle
      combining the high plastid gene content of the Porphyra purpurea rhodoplast and
      the peptidoglycan wall of glaucocystophyte cyanelles. This means that the import
      apparatus of all primary plastids should be homologous. Indeed, heterologous in
      vitro import can now be shown in both directions, provided a phenylalanine
      residue essential for cyanelle import is engineered into the N-terminal part of
      chloroplast transit peptides. The cyanelle and likely also the rhodoplast import
      apparatus can be envisaged as prototypes with a single receptor showing this
      requirement for N-terminal phenylalanine. In chloroplasts, multiple receptors
      with overlapping and less stringent specificities have evolved explaining the
      efficient heterologous import of native precursors from C. paradoxa. With respect
      to conservative sorting in cyanelles, both the Sec and Tat pathways could be
      demonstrated. Another cyanobacterial feature, the dual location of the Sec
      translocase in thylakoid and inner envelope membranes, is also unique to
      cyanelles. For the first time, protease protection of internalized lumenal
      proteins could be shown for cyanobacteria-like, phycobilisome-bearing thylakoid
      membranes after import into isolated cyanelles.

PMID- 16092531
TI  - Peroxisomes, glyoxysomes and glycosomes (review).
AB  - Peroxisomes, glyoxysomes and glycosomes are related organelles found in different
      organisms. The morphology and enzymic content of the different members of this
      organelle family differ considerably, and may also be highly dependent on the
      cell's environmental conditions or life cycle. However, all peroxisome-like
      organelles have in common a number of characteristic enzymes or enzyme systems,
      notably enzymes dealing with reactive oxygen species. All organelles of the
      family follow essentially the same route of biogenesis, but with species-specific
      differences. Sets of proteins called peroxins are involved in different aspects
      of the formation and proliferation of peroxisomes such as import of proteins in
      the organellar matrix, insertion of proteins in the membrane, etc. In different
      eukaryotic lineages these functions are carried out by often--but not always-
      homologous yet poorly conserved peroxins. The process of biogenesis and the
      nature of the proteins involved suggest that all members of the peroxisome family
      evolved from a single organelle in an ancestral eukaryotic cell. This original
      peroxisome was possibly derived from a cellular membrane system such as the
      endoplasmic reticulum. Most of the organism-specific functions of the extant
      organelles have been acquired later in evolution.

PMID- 16092532
TI  - Facts about CORLAS.

PMID- 16092533
TI  - Study of a temporal bone of Homo heildelbergensis.
AB  - CONCLUSIONS: The characteristic features of the Hh specimen conformed to those of
      other Pleistocene human fossils, indicating strong cranial structures and a heavy
      mandible. The mastoid was large and suggested a powerful sternocleidomastoid
      muscle. The inner ear and tympanic cavities were similar in size and orientation,
      suggesting that their functions were probably similar. Our observations suggest
      that the left ear of this Hh specimen was healthy. The large canaliculo-fenestral
      angle confirms that this ancestor was bipedal. It also strongly suggests that Hh
      individuals were predisposed to develop certain pathologies of the labyrinth
      capsule associated with bipedalism, in particular otosclerosis. OBJECTIVE: We
      studied a temporal bone of Homo heidelbergensis (Hh) in order to investigate the
      clinical and physiological implications of certain morphological features,
      especially those associated with the evolutionary reorganization of the inner
      ear. MATERIAL AND METHODS: The bone, found in a breach of a cave near MAaaga in
      southern Spain, together with Middle Upper Pleistocene faunal remains, is >300000
      years old. Four analytical methods were employed. A 3D high-resolution surface
      laser scan was used for anatomical measurements. For the sectional analysis of
      the middle and inner ears of Hh we used high-resolution CT, simultaneously
      studying a normal temporal bone from Homo sapiens sapiens (Hss). To study the
      middle and inner ear spaces we used 3D reconstruction CT preceded by an intra
      bone air shielding technique. To examine the tympanic cavities and measure the
      canaliculo fenestral angle, we used a special minimally invasive endoscopic
      procedure. RESULTS: The surface, sectional and 3D CT examinations showed that the
      Hh specimen was generally more robust and larger than the Hss specimen. It had a
      large glenoid fossa. The external meatus was wide and deep. The middle ear, and
      especially the mastoid, was large and widely pneumatized. There were no
      appreciable differences in the position and size of the labyrinthine spaces and
      tympanic cavity. The dimensions of the semicircular canals were similar to those
      of the Hss specimen. Endoscopy revealed normal, healthy tympanic walls and an
      ossicle fragment in the atticum that probably belonged to the body of the
      malleus. The diameters of the fallopian duct and the tympanic opening of the
      Eustachian tube were large. The canaliculo-fenestral angle was approximately 114
      degrees

PMID- 16092534
TI  - Sign language: its history and contribution to the understanding of the
      biological nature of language.
AB  - CONCLUSION: The development of conceptualization of a biological basis of
      language during the 20th century has come about, in part, through the
      appreciation of the central nervous system's ability to utilize varied sensory
      inputs, and particularly vision, to develop language. OBJECTIVE: Sign language
      has been a part of the linguistic experience from prehistory to the present day.
      Data suggest that human language may have originated as a visual language and
      became primarily auditory with the later development of our voice/speech tract.
      Sign language may be categorized into two types. The first is used by individuals
      who have auditory/oral language and the signs are used for special situations,
      such as communication in a monastery in which there is a vow of silence. The
      second is used by those who do not have access to auditory/oral language, namely
      the deaf. MATERIAL AND METHODS: The history of the two forms of sign language and
      the development of the concept of the biological basis of language are reviewed
      from the fourth century BC to the present day. RESULTS: Sign languages of the
      deaf have been recognized since at least the fourth century BC. The codification
      of a monastic sign language occurred in the seventh to eighth centuries AD.
      Probable synergy between the two forms of sign language occurred in the 16th
      century. Among other developments, the Abbey de L'Epee introduced, in the 18th
      century, an oral syntax, French, into a sign language based upon indigenous signs
      of the deaf and newly created signs. During the 19th century, the concept of a
      "critical" period for the acquisition of language developed; this was an
      important stimulus for the exploration of the biological basis of language. The
      introduction of techniques, e.g. evoked potentials and functional MRI, during the
      20th century allowed study of the brain functions associated with language.

PMID- 16092535
TI  - Latin American experience with the cochlear implant.
AB  - CONCLUSIONS: Complications such as migration, extrusion, skin inflammation by
      magnets and implant failures are mostly related to the type of device. Meticulous
      technique rather than specific surgical approaches seems to be the key in
      avoiding complications. The overall results of the Latin American experience are
      comparable with those reported recently in the literature. OBJECTIVE: To review
      the experience of Latin American groups with the cochlear implant. MATERIAL AND
      METHODS: A questionnaire was sent to all cochlear implant teams in Latin America.
      The main questions involved: (i) the type of device; (ii) the techniques used for
      placing and fixing the implant, surgical incision and closure; (iii) migration,
      exposure and failure of the implant; and (iv) skin erosion and infection. A total
      of 41 groups participated in the study. The total number of implanted patients
      involved was 3773, representing 92% of Latin American cases. RESULTS: Of the 3773
      devices implanted, 5 were experimental prototypes and therefore 3768 were
      considered for calculations. The occurrence of complications was as follows.
      Migration: 13 cases (0.35%), mostly related to ceramic implants (p =0.016).
      Extrusion: 15 cases (0.4%), mostly related to large implants (p =0.0103). Implant
      failure secondary to trauma: 18 cases (0.48%) (9 in ceramic and 9 in soft
      implants). Spontaneous failure: 86 cases (2.28%), 74/1293 (5.72%) in ceramic and
      11/2418 (0.45%) in soft implants (p = 0.0001). The most reliable implant was the
      Nucleus 24, with a failure rate of 0.3%. Skin inflammation by magnet: 35 cases
      (0.9%), mostly related to soft implants (p =0.0103). INFECTION: 26 cases (0.7%),
      with no significant relationship to device type.

PMID- 16092536
TI  - Measurements of electrode position inside the cochlea for different cochlear
      implant systems.
AB  - CONCLUSIONS: This study demonstrates that the exact location of an electrode
      inside the cochlea needs to be assessed using two complementary measures, namely
      the length and angle of insertion, both of which are mandatory if one wants to
      prevent erroneous outcomes. Knowledge of the contact position may become very
      useful when tuning a cochlear implant processor in a patient with contralateral
      residual hearing, or in cases of binaural implants. OBJECTIVE: Multichannel
      cochlear implants restore useful hearing to deaf patients. However, several types
      of intracochlear electrodes are presently available, each featuring a specific
      technology or design. The aim of this study was to determine precisely the
      intracochlear position of the contacts for different electrode arrays. MATERIAL
      AND METHODS: Electrode array insertions were estimated using special radiographs.
      A total of 26 cochlear implantations were included in the study: 6 Ineraid; 5
      Clarion HiFocus I; 11 Clarion HiFocus II; and 4 Med-El Combi40+. In each case, a
      measurable reference or marker ring placed close to the round window (within 2
      mm) could be identified. Insertion lengths and angles were measured and then
      plotted on a graphl based on 3D reconstructions. RESULTS: Both Clarion HiFocus I
      and II electrode arrays were found to be placed close to the inner wall of the
      cochlea. Ineraid and Med-El Combi40+ electrode arrays were both placed close to
      the organ of Corti, the Med-El Combi40+ arrays demonstrating the deepest
      insertions overall. In spite of marked differences in the positions of the
      contacts, we did not find any correlation with speech perception performance for
      the different types of implants studied.

PMID- 16092537
TI  - Preservation of residual hearing with cochlear implantation: how and why.
AB  - CONCLUSIONS: Hearing may be conserved in adults after implantation with the
      Nucleus Contour Advance perimodiolar electrode array. The degree of hearing
      preservation and the maximum insertion depth of the electrode array can vary
      considerably despite a defined surgical protocol. Residual hearing combined with
      electrical stimulation in the same ear can provide additional benefits even for
      conventional candidates for cochlear implantation. OBJECTIVES: We present
      preliminary results from a prospective multicentre study investigating the
      conservation of residual hearing after implantation with a standard-length
      Nucleus Contour Advance perimodiolar electrode array and the benefits of combined
      electrical and acoustic stimulation. MATERIAL AND METHODS: The subjects were 12
      adult candidates for cochlear implantation recruited according to national
      selection criteria. A "soft" surgery protocol was defined, as follows: 1-1.2-mm
      cochleostomy hole anterior and inferior to the round window; Nucleus Contour
      Advance electrode array inserted using the "Advance-off-stylet" technique; and
      insertion depth controlled by means of three square marker ribs left outside the
      cochleostomy hole. These procedures had been shown to reduce insertion forces in
      temporal bone preparations. Variations in surgical techniques were monitored
      using a questionnaire. Pure-tone thresholds were measured pre- and
      postoperatively. Patients who still retained thresholds <90 dB HL for frequencies
      up to 500 Hz were re-fitted with an in-the-ear (ITE) hearing aid. Word
      recognition was tested in quiet and sentence perception in noise for the cochlear
      implant alone and in combination with an ipsilateral hearing aid. RESULTS:
      Hearing threshold level data were available for 12 patients recruited from 6 of
      the centres. Median increases in hearing threshold levels were 23, 27 and 33 dB
      for the frequencies 125, 250 and 500 Hz, respectively. These median increases
      include the data for two patients who had total loss of residual hearing due to
      difficulties encountered during surgery. "Cochlear view" X-ray images indicated
      that the depth of insertion varied between 300 and 430 degrees, despite modest
      variations in the length of the electrode inserted (17-19 mm). The insertion
      angle had some influence on the preservation of residual hearing at frequencies
      of 250-500 Hz. Six of the 12 patients retained sufficient hearing for effective
      use of an ipsilateral ITE hearing aid (< or = 80 dB HL at 125 and 250 Hz; < or =
      90 dB HL at 500 Hz). Word recognition scores in quiet were improved from 10% to
      30% with the cochlear implant plus ipsilateral hearing aid in 3 patients who had
      at least 3 months postoperative experience. Signal:noise ratio thresholds for
      sentence recognition were improved by up to 3 dB. Patients reported that they
      experienced greatly improved sound quality and preferred to use the two devices
      together.

PMID- 16092538
TI  - Auditory brainstem response and otoacoustic emission assessment of hearing
      impaired children of mothers who contracted rubella during pregnancy.
AB  - CONCLUSIONS: Based on the auditory brainstem response (ABR) results obtained in
      this study, the incidence of deafness in children whose mothers had rubella
      during pregnancy is high (29.5%), and deafness is profound in most cases (80%).
      Vaccinating women of childbearing age against rubella is essential to reduce the
      number of cases of childhood sensorineural hearing loss caused by gestational
      rubella. OBJECTIVE: It has been shown in the literature that, in Brazil,
      gestational rubella is responsible for approximately 21% of cases of deafness in
      children. The purpose of this study was to assess the incidence of deafness in
      children whose mothers had rubella during pregnancy. MATERIAL AND METHODS:
      Between February and July 2001, we conducted a prospective study assessing
      hearing status in 17 children (mean age 6 months). The mothers had serologically
      (ELISA) confirmed gestational rubella. We recorded ABRs and analysed distortion
      product otoacoustic emissions (DPOAEs). RESULTS: In 5 children (29.5%), ABRs
      revealed sensorineural hearing loss, which was moderate to severe in 1 (20%) and
      profound in 4 (80%). The hearing loss was bilateral in 3 children (60%) and
      asymmetrical in 4 (80%). Regarding DPOAEs, 7 children (41%) presented no
      response, and this occurred bilaterally in 4 (57%). All children with abnormal
      ABRs also presented abnormal DPOAEs. Two children with normal ABRs presented
      abnormal DPOAEs.

PMID- 16092539
TI  - Dissociated eye movements: a clinical study.
AB  - CONCLUSIONS: Dissociation of eye movements is an important sign of functional or
      organic lesions of the central vestibular system. Qualitative differences in the
      movements of each eye appear to be more serious than quantitative differences.
      OBJECTIVE: To determine the significance of dissociated nystagmus in
      neurotological diagnosis. MATERIAL AND METHODS: Eye movements were recorded
      separately for each eye during the neurotological examination of patients with a
      suspicion of central vestibular system involvement. RESULTS: Of 137 patients, 38
      had quantitative dissociation of eye movements and 59 had qualitative
      differences. A total of 66/137 patients had abnormal MRI scans: 55 of these
      patients presented dissociated eye movements and only 39 had other signs of
      central vestibular involvement.

PMID- 16092540
TI  - Head-body righting reflex from the supine position and preparatory eye movements.
AB  - CONCLUSION: Saccular and utricular maculae can provide information on the supine
      static position, considering that both have pronounced curved structures with
      hair cells having a variety of polarization vectors that enable them to sense an
      inverted position and thus direct the righting reflex. OBJECTIVE: The vestibular
      system is essential for the structuring of motor behaviour, senses linear and
      angular acceleration and has a strong influence on posture and balance at rest,
      during locomotion and in head body righting reflexes. MATERIAL AND METHODS: Using
      guinea pigs in the supine position with a symmetrical head and trunk position,
      the ocular position was analysed to ascertain whether any ocular movement that
      occurred would adopt a spatial deviation indicative of the subsequent head and
      body righting. The characteristics of the righting reflex (direction, latency,
      duration and velocity) were analysed in guinea pigs from position signals
      obtained from search coils implanted in the eye, head and pelvis. The animals
      were kept in a supine position for a few seconds or even minutes with the eyes in
      a stable primary position and the head and body symmetrical and immobile.
      RESULTS: The righting reflex took place either immediately or after a slow
      deviation of the eyes. In both cases the righting sequence (eyes, head, body) was
      stereotyped and consistent. The direction of head and body righting was along the
      longitudinal axis of the animal and was either clockwise or anticlockwise and the
      direction of righting was related to the direction of the eye deviation. The
      ocular deviation and the direction of deviation that initiated and determined the
      direction of the righting reflex could be explained by possible otolithic
      activation.

PMID- 16092541
TI  - Assessment and amelioration of hyperacusis in tinnitus patients.
AB  - CONCLUSIONS: Tinnitus can be bothersome even without hyperacusis. The good
      correlation found in this study between the multiple-activity scale for
      hyperacusis (MASH) score and the overall annoyance of hyperacusis score supports
      the reliability of self-rating of hyperacusis. Objectives. A prospective study
      was undertaken to investigate the relationships between hyperacusis and tinnitus
      and to determine whether hyperacusis can be rapidly controlled over time.
      MATERIAL AND METHODS: All tinnitus patients seen over a period of 16 months with
      surnames beginning with the letters A L (n = 249) were assessed during a
      structured interview using (i) a scale ranging from 0 to 10 for assessing the
      annoyance of tinnitus and the overall annoyance of hyperacusis and (ii) the newly
      introduced MASH. RESULTS: The annoyance of tinnitus was greater in females. The
      prevalence of hyperacusis was high (79%). The annoyance of hyperacusis varied.
      Patients were categorized into five groups according to the hyperacusis annoyance
      score, as follows: no hyperacusis; mild hyperacusis (< or = 3); moderate
      hyperacusis (3.1-5.0); substantial hyperacusis (5.1-7.0); and severe hyperacusis
      (> or = 7.1). Individuals with severe hyperacusis were younger than those in the
      other groups. The correlation between the annoyance of tinnitus and the annoyance
      of hyperacusis was poor (r = 0.35). No audiometric difference was found between
      categories, whereas self-rated hearing deficiency increased with the annoyance of
      hyperacusis. A good correlation (r = 0.89) was found between the overall
      annoyance of hyperacusis and the MASH score. Changes over time, assessed in 32
      patients investigated at least 3 times, showed more frequent improvement in
      hyperacusis (63%) than tinnitus (47%).

PMID- 16092542
TI  - Coenzyme Q-10 treatment of patients with a 7445A--->G mitochondrial DNA mutation
      stops the progression of hearing loss.
AB  - CONCLUSION: CoQ 10 may be helpful in delaying the progression of hearing loss in
      patients with the 7445A-->G mitochondrial mutation. Objective. To assess the
      effect of an antioxidant drug (Coenzyme Q-10) on the hearing level of patients
      with the mitochondrial DNA 7445A-->G mutation and associated sensorineural
      hearing loss (SNHL). Material and methods. We identified three patients with
      bilateral non-syndromic SNHL harboring the mitochondrial 7445A-->G mutation. Two
      patients had a family history of hearing loss with a strong matrilineal
      inheritance. The other patient did not have a family history of hearing loss. Two
      patients (1 with familial and 1 with sporadic SNHL) received treatment with 75 mg
      of Coenzyme Q-10 (CoQ10) twice a day for 1 year. The remaining patient with a
      familial form of hearing loss did not agree to take the treatment. Average bone
      conduction pure-tone thresholds for 0.5, 1, 2 and 4 kHz were obtained before and
      after diagnosis of mitochondrial hearing loss, and before and after treatment
      with CoQ10. Results. CoQ10-treated patients did not show any additional
      deterioration of their SNHL after 12 (familial case) and 13 months (sporadic
      case). The progression rate of SNHL was 6 dB/year in the 2 years prior to
      initiation of treatment in the familial case who received CoQ10 treatment. One
      year after being diagnosed with mitochondrial hearing loss, the patient who
      refused CoQ10 treatment exhibited an 11-dB deterioration of his hearing
      thresholds. There were no side-effects related to treatment with CoQ10.

PMID- 16092543
TI  - Functional studies of the human auditory pathway after monaural stimulation with
      pure tones. Establishing a normal database.
AB  - CONCLUSIONS: Bilateral activation of Brodmann area 39 provides functional support
      for the concept of bilateral cortical activation with auditory stimulation. The
      observation that when Brodmann area 39 is activated, area 38 of the temporal lobe
      is simultaneously inhibited (a functional observation that has seemingly not been
      previously reported) supports the concept that inhibitory as well as excitatory
      relays play a role in the auditory pathways. In addition, this report helps to
      establish a functional database for future studies. OBJECTIVES: (i) To determine
      which areas of the cerebral cortex and basal ganglia are activated when the left
      and right ears are monaurally stimulated with pure tones, and what type of
      response (e.g. excitatory or inhibitory) occurs in these different areas. (ii) To
      determine the degree of ipsi- and/or contralateral cortical activation and/ or
      inhibition depending on the ear that is stimulated. (iii) To use this information
      as an initial step to develop a normal functional database for future studies.
      MATERIAL AND METHODS: A brain perfusion single-photon emission CT (SPECT)
      evaluation was conducted using auditory monaural stimulation with pure tones in
      10 normal volunteers. Both ears were tested independently (20 examinations in
      total). 99mTc hexamethyl-propylenamine-oxime was injected while pure tones were
      delivered, and the SPECT imaging was done 1 h later. RESULTS: After delivering
      pure tones there was bilateral cortical activation in Brodmann areas 39 and 40,
      regardless of which ear was stimulated. Despite marked hyperperfusion in both
      areas 39, a more intense response was seen on the left compared to the right
      side, although this was not statistically significant. There was also activation
      in the executive frontal cortex areas 9 and 10 as well as in the temporal
      Brodmann areas 21 and 22. Simultaneously, area 38 of the temporal lobe was
      deactivated. In the subcortical structures there was also marked activation in
      both thalami and deactivation of the caudate nuclei without lateralization.

PMID- 16092544
TI  - Effects of efferent acoustic reflex activation on psychoacoustical tuning curves
      in humans.
AB  - CONCLUSIONS: The results show that, in humans, activation of the contralateral
      EAR makes the PTC narrower at 1 kHz but wider at 4 kHz. These data are consistent
      with those reported previously in animals and demonstrate that, during medial
      efferent stimulation in humans, frequency resolution is improved at low
      frequencies but impaired at high frequencies. OBJECTIVE: To evaluate, in humans,
      the effect of activation of the contralateral efferent acoustic reflex (EAR) on
      the psychoacoustical tuning curves (PTCs) recorded for 1- and 4-kHz probe tones.
      MATERIAL AND METHODS. Ten young (20-30 years) volunteers served as subjects. They
      had normal hearing (thresholds <20 dB HL in the frequency range 0.25-8 kHz) and a
      functioning EAR (contralateral suppression of transient-evoked otoacoustic
      emissions > or = 0.8 dB). Frequency resolution was evaluated using PTCs. PTCs
      were recorded at 1 and 4 kHz using a simultaneous masking method. Q10 and Q20
      were calculated as the ratio between the test frequency and the bandwidth of the
      PTC at 10 and 20 dB above the tip of the curve, respectively. The EAR was
      activated with a 40-dB SL contralateral narrow-band noise centered on the
      characteristic frequency of the PTC (1 or 4 kHz). Q10 and Q20 were measured in
      the presence and absence of the contralateral noise. RESULTS: Activation of the
      EAR led to a significant increase (p < 0.001) in Q10 at 1 kHz and a significant
      decrease (p <0.001) at 4 kHz. Changes in the value of Q20 were not significant.

PMID- 16092545
TI  - Contribution of self-motion perception to acoustic target localization.
AB  - CONCLUSION: The findings of this study suggest that acoustic spatial perception
      during head movement is achieved by the vestibular system, which is responsible
      for the correct dynamic of acoustic target pursuit. OBJECTIVE: The ability to
      localize sounds in space during whole-body rotation relies on the auditory
      localization system, which recognizes the position of sound in a head-related
      frame, and on the sensory systems, namely the vestibular system, which perceive
      head and body movement. The aim of this study was to analyse the contribution of
      head motion cues to the spatial representation of acoustic targets in humans.
      MATERIAL AND METHODS: Healthy subjects standing on a rotating platform in the
      dark were asked to pursue with a laser pointer an acoustic target which was
      horizontally rotated while the body was kept stationary or maintained stationary
      while the whole body was rotated. The contribution of head motion to the spatial
      acoustic representation could be inferred by comparing the gains and phases of
      the pursuit in the two experimental conditions when the frequency was varied.
      RESULTS: During acoustic target rotation there was a reduction in the gain and an
      increase in the phase lag, while during whole-body rotations the gain tended to
      increase and the phase remained constant. The different contributions of the
      vestibular and acoustic systems were confirmed by analysing the acoustic pursuit
      during asymmetric body rotation. In this particular condition, in which self
      motion perception gradually diminished, an increasing delay in target pursuit was
      observed.

PMID- 16092546
TI  - Technical pitfalls in middle ear gas studies: errors introduced by the gas
      permeability of tubing and additional dead space.
AB  - CONCLUSIONS: We demonstrated errors introduced by the gas permeability of the
      tubing and additional dead space. Materials with practically no permeability,
      such as glass, must be used to overcome the loss or gain of gas through the walls
      of tubes used for studying ME gas variations. Experiments conducted at a constant
      volume (variable pressure) require the smallest possible tubing volume in order
      to obtain good sensitivity and improve the accuracy of the results. OBJECTIVES:
      Experimental studies that investigate middle ear (ME) gas exchanges, using either
      pressure measurements or volume changes, are conducted using various tubing
      connections between the ME and a measuring device. The aims of this study were to
      highlight experimental problems due to the errors introduced by (i) the gas
      permeability of the tubing used and (ii) additional dead space in experiments
      conducted at constant volume. MATERIAL AND METHODS: The problem of the gas
      permeability of the tubing was addressed by comparing three types of tube
      (silicone, polyethylene, PVC) with a glass tube. Horizontally placed tubes were
      connected to a syringe filled with pure CO2 via a gas-tight valve. The end of
      each tube tested was plunged into colored water (5% Coomassie Brilliant Blue R
      250). The tube was washed out with CO2 until gas bubbles were seen leaving it.
      The valve was then closed and the movement of water in the tube was observed. The
      same experiments were repeated for pure O2. The problem of the error introduced
      by the additional dead space volume was addressed at a theoretical level using
      the well-known gas laws. Two conditions were studied: condition A, in which the
      experiment was conducted at constant pressure and the volume was measured; and
      condition B, in which the experiment was conducted at constant volume and the
      pressure was measured. The main outcome measure of each condition was the
      calculated variation in the final number of moles of gas involved. RESULTS: No
      water movement was observed in glass tubes. In contrast, plastic tubes exhibited
      significant gas permeability effects for both CO2 and O2. The colored solution
      advanced at a faster rate with CO2 than O2 but differently for each type of
      tubing. For condition A, gas transfer was independent of the volume of the
      external tubing and was accurately measured by the displacement of the droplet in
      the lumen. In contrast, for condition B, the pressure variations were influenced
      by the volume of the tubing.

PMID- 16092547
TI  - Ultrastructure of the normal human organ of corti. new anatomical findings in
      surgical specimens.
AB  - CONCLUSION: A thorough scanning electron microscopy (SEM) investigation of
      immediately fixed human adult cochleae obtained during surgery for petro-clival
      meningiomas conveyed new information about morphology. OBJECTIVE: To investigate
      the ultrastructure of human adult cochleae using SEM. MATERIAL AND METHODS: Two
      human cochleae were decalcified, fixed with glutaraldehyde and osmium and
      prepared for SEM. RESULTS: The excellently preserved morphology showed the
      pathways of nerve fibres through the organ of Corti. Undulating lateral cell
      membranes of Hensen and Claudius cells created an enlarged surface that may be
      important for homoeostasis. The distal attachment of the tectorial membrane to
      the reticular lamina was present in the shape of a marginal net, which was
      extended through marginal pillars. Stereocilia imprints extended as far as the
      distal end of the marginal pillars. The presence of an irregularly distributed
      fourth row of outer hair cells attached to the marginal pillars raises questions
      about differences in the excitation of the last row of outer hair cells as a
      result of differences in the composition of the tectorial membrane.

PMID- 16092548
TI  - Reversibility of experimental cholesteatoma epithelium using Mongolian gerbils.
AB  - CONCLUSION: The results of this study encourage our belief that some
      cholesteatomas can be managed using only conservative treatments. OBJECTIVE: We
      hypothesized that once cholesteatoma is in a normal environment, its cellular or
      molecular pathology can revert to those characteristic of normal epidermis. The
      aim of this study was to determine whether or not common molecular
      characteristics of cholesteatoma were reversible after removal of inductive
      factors in experimental cholesteatoma induced in gerbils. MATERIAL AND METHODS:
      We induced cholesteatoma using ear canal ligation in Mongolian gerbils. After
      ligation, the animals in the treated group were managed for 2 weeks. We examined
      differences between treated and untreated cholesteatomas using terminal
      deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) staining and
      an immunohistochemical technique using the proliferation markers proliferating
      cell nuclear antigen (PCNA) and cytokeratin (CK). RESULTS: With PCNA and CK
      13/16, the untreated group showed positive staining in the suprabasal and basal
      cells, but the treated group showed weakly positive staining only in the basal
      cell layer. With TUNEL staining, there were more positive cells in the untreated
      than the treated group.

PMID- 16092549
TI  - Electromotile performance of isolated outer hair cells during slow motile
      shortening.
AB  - CONCLUSION: The electromotile performance of isolated OHCs does not seem to be
      dependent on slow motile shortening alone; other mechanisms, such as
      phosphorylation, are also involved. OBJECTIVE: To elucidate the relationship
      between the magnitude of electromotile displacements and magnitude of slow motile
      shortening of outer hair cells (OHCs) induced by mechanical or chemical
      stimulation over a reversible range. MATERIAL AND METHODS: Isolated guinea pig
      OHCs were mechanically (0.6 microl/min perfusion of saline; n =4) or chemically
      and mechanically (0.6 microl/min perfusion of 12.5 mM KCl; n =4) stimulated in a
      glass microchamber to evoke slow motile shortening. RESULTS: Combined mechanical
      and chemical stimulation evoked greater OHC shortening than mechanical
      stimulation alone. Both forms of stimulation resulted in reversible shortening.
      Electromotility was measured using low voltage (+/- 35 mV) and higher voltage (up
      to +/- 240 mV) electrical pulses mimicking the receptor potential at different
      stages of cell shortening. The magnitude of electromotility decreased
      simultaneously with slow motile shortenings of OHCs. Irrespective of the
      character of the stimulus (mechanical or mechanical + chemical), the decrease in
      the magnitude of electromotility was dependent on the degree of cell shortening.
      Ocadaic acid, a protein phosphatase inhibitor, blocked slow motility and
      decreased the magnitude of electromotility.

PMID- 16092550
TI  - Role of alcohol and smoking in diagnostic delay of head and neck cancer patients.
AB  - CONCLUSIONS: This study shows that heavy drinking is a risk factor for prolonged
      delay in presenting with head and neck cancer and for presenting with a large
      tumour in the head and neck region. Excessive smoking is only a risk factor for
      being diagnosed with a large tumour, although there is a weak association between
      smoking and prolonged diagnostic delay. OBJECTIVE: It is reasonable to assume
      that prolonged delay in presenting with head and neck cancer is associated with
      an advanced stage of cancer at diagnosis. In this study we analysed the effects
      of drinking and smoking habits on diagnostic delay and the T stage of the tumour
      at diagnosis. MATERIAL AND METHODS: A total of 427 patients with newly diagnosed
      head and neck carcinomas were eligible for this study. Of these, 306 (72%)
      actually participated: 134 (77%) with an oral tumour; 117 (69%) with a larynx
      tumour; and 55 (65%) with a pharynx tumour. Diagnostic delay was defined as a
      period of >30 days between the appearance of the first tumour-related symptoms
      and the first visit to a physician. T3 4 tumours were defined as advanced
      tumours. Drinking behaviour was classified into three types: light (0 2
      drinks/day); moderate (3 4 drinks/day); and heavy ( >4 drinks/day). Smoking
      habits were classified into 4 types: never; stopped; light (0 20 cigarettes/day);
      and heavy (>20 cigarettes/day). RESULTS: Logistic regression showed that there
      were significantly more heavy than light drinkers [p = 0.04; odds ratio (OR) 1.8;
      95% CI 1.0-3.1] in the delay group than in the non-delay group. Light smokers
      showed a tendency towards prolonged delay (p = 0.06; OR 2.2; 95% CI 1.0-5.0).
      Both heavy drinking (p = 0.01; OR 2.0; 95% CI 1.2-3.6) and heavy smoking (p =
      0.03; OR 3.1; 95% CI 1.1-8.4) were risk factors for a patient to be diagnosed
      with a large tumour.

PMID- 16092551
TI  - Mood, anxiety and sense of humor in head and neck cancer patients in relation to
      disease stage, prognosis and quality of life.
AB  - CONCLUSION: At diagnosis, control patients had the lowest depression levels and
      anxiety scores, followed by those with limited HNSCC disease and these with
      extended HNSCC disease. Anxiety and depression levels at diagnosis predicted
      prognosis via an association with extent of disease. Sense of humor, but not
      anxiety or depression level, predicted lower QoL and depression levels at follow
      up. OBJECTIVE: To study the association between anxiety score, depression level
      at sense of humor at diagnosis in head and neck squamous cell carcinoma (HNSCC)
      patients versus TNM stage, prognosis and depression level/quality of life (QOL) 6
      years following diagnosis. A control group of patients with benign HN disease was
      also included. MATERIAL AND METHODS: Male patients with newly diagnosed HNSCC (n
      =78) or benign HN (n =61) disease completed the following questionnaires: the
      Beck Depression Inventory, the Spielberger Trait Anxiety Inventory (state) and
      the Svebak humor questionnaire. Patients with cachexia or those aged >80 years
      were excluded. In the HNSCC patients, TNM stage, prognosis and QOL/depression
      level (n =27) were determined following successful therapy. RESULTS: HNSCC
      patients reported high anxiety scores and lower depression levels than control
      patients, although there was overlap between the groups. N stage was associated
      with high anxiety scores and depression levels, whereas T stage was only
      associated with depression levels. Both anxiety scores and depression levels at
      diagnosis predicted prognosis through an association with TNM stage. Sense of
      humor, but not depression levels or anxiety scores, at diagnosis predicted QoL
      and depression levels at follow-up.

PMID- 16092552
TI  - Preliminary study of the lymphatic drainage system of the nose and paranasal
      sinuses and its role in detection of sentinel metastatic nodes.
AB  - CONCLUSIONS: The normal nasal lymphatic drainage runs via the facial vessels into
      the neck lymphatic nodes of levels I-II and this drainage pattern was found in
      our patients with sinonasal tumors. We found only one true-positive sentinel
      lymph node (SLN). Our pathological material was very limited and so further
      investigations are required before any valid conclusions can be drawn concerning
      the clinical value of SLNs in nasal tumors. Objectives. To detect the lymph
      collection route of the nasal fossae and paranasal sinuses and to identify the
      first echelon in the tumor metastatic cascade in order to prevent the risk of
      occult metastases in N0 necks in patients with primary head and neck squamous
      cell carcinoma (SCC). MATERIAL AND METHODS: Our control group comprised 30
      patients (20 females; age range 19-50 years) suffering from chronic otitis media
      who had an anatomically normal nose and a cNO neck on palpation. The pathological
      group comprised 6 patients (2 females; age range 40-85 years) suffering from
      sinonasal tumors: 3 SCC, 1 recurrent melanoma, 1 ameloblastoma and 1 inverted
      papilloma. All had a clinically staged cNO neck on palpation and CT. In the
      control group, lymphoscintigraphy was carried out by means of unilateral
      injection of radioactive gold into the head of the inferior turbinate. The tracer
      was identified using a gamma camera 3 and 6 h after the injection. In the
      pathological group the chosen tracer was technetium, which was administered 1 day
      prior to surgery by means of injections into the heads of the inferior and middle
      turbinates, into the nasal septum and into the retromaxillary gingival mucosa.
      The tracer was identified transcutaneously using a navigator probe in the gamma
      camera at 15 min, 30 min and 1 h post-injection. A mark was drawn on the skin
      corresponding to the hot spot of the SLN. The study was repeated 30 min before
      surgery. The neck incision was selected according to the location of the SLN. A
      hand-held gamma probe was used in the operating theatre to detect in situ the
      radioactivity of the surgical excisional nasal area and the cervical SLN. Once
      the SLN was excised its radioactivity was confirmed ex situ, taking into account
      that the activity counts were at least three times greater than background.
      Postoperatively, all SLNs were histopathologically examined and cytokeratin
      staining was carried out immunohistochemically using the monoclonal antibody
      cocktail AE1/AE3. Results. In the control group, intense activity at the
      injection tracer site and lower activity in the submandibular area (level I) were
      detected in 26.6% of cases. Nasal radioactivity persisted for 6 h post-injection
      and submandibular radioactivity increased, also reaching the area corresponding
      to neck node level II (70%). In two cases (6.6%), radioactivity was observed in
      the retropharyngeal nodes. In the pathological group, the SLN was found in the
      submandibular area (level I) in three cases, and in the ameloblastoma patient
      three SLNs were found at levels I-II. Three cases were false positives, and no
      metastases were detected using any of the histopathological procedures. The only
      one true positive corresponded to a female with an SCC of the maxillary
      infrastructure with invasion of the gingival mucosa. The histopathological code
      was 1 and a metastasis was detected on hematoxylin-eosin examination. In the
      other two cases no SLNs were detected.

PMID- 16092553
TI  - Comparison of ciliary wave disorders measured by image analysis and electron
      microscopy.
AB  - CONCLUSION: We have developed a simple, reliable method for the simultaneous
      determination of the ciliary wave disorder (CWD) and ciliary beat frequency (CBF)
      of actively beating cilia. OBJECTIVE: The CBF and the directions of beating cilia
      are two important components of mucociliary transport. Although lots of studies
      have been performed on the measurement of the CBF, there have been few studies on
      the direction of cilia, with the exception of those using electron microscopy
      (EM). EM takes too long to determine the directions of cilia, and it cannot
      determine the direction of actively beating cilia. The aim of this study was to
      develop an image analysis (IA) system to conveniently determine the wave
      directions of multiple actively beating cilia as well as the CBF. MATERIAL AND
      METHODS: Sphenoid sinus mucosae obtained from 10 patients undergoing pituitary
      tumor removal via a trans-septal trans-sphenoidal approach were divided into two
      4 x 4 mm2-sized pieces. One piece was studied using IA, the other with EM. Using
      IA, ciliary wave directions were determined from 5 20 x 20 microm2 regions of
      interest and the mean of 5 consecutive values was regarded as the CWD of each
      sample. The CBF was also measured. CWD was also measured using EM. RESULTS: The
      average number of cilia analyzed by EM was 102.50 (range 48-136). The mean CWDs
      determined using IA and EM were 28.25+/-4.84 degrees and 23.59+/-8.16 degrees,
      respectively. There was a significant correlation between the CWDs determined
      using these two methods (Spearman's correlation coefficient =0.648; p =0.043).
      The mean CBF of sphenoid mucosa was 10.50+/-2.20 Hz.

PMID- 16092554
TI  - A profession of partners.

PMID- 16092555
TI  - Should the parents be present during the pediatric exam?

PMID- 16092556
TI  - Just be the dentist!

PMID- 16092557
TI  - Accounting basics for the hygienist: understanding office economics.

PMID- 16092558
TI  - Same-day implant placement and provisionalization for single-tooth implants: a
      technique update and review of clinical experiences.

PMID- 16092559
TI  - Treatment planning for dental implants: a rationale for decision making. Part 2:
      Partial edentulism.

PMID- 16092561
TI  - Altering and controlling osseous architecture to achieve an aesthetic dentition.

PMID- 16092560
TI  - Immediate extraction site grafting: materials and clinical objectives.

PMID- 16092562
TI  - Blue-collar cosmetics: alternative approaches to building beautiful smiles.

PMID- 16092563
TI  - Endodontic K-files: invaluable endangered species or ready for the Smithsonian?

PMID- 16092564
TI  - A new paradigm in tooth preparation.

PMID- 16092565
TI  - Assessing patient readiness for full-mouth restoration: a case report.

PMID- 16092567
TI  - Becoming a fee-for-service dental practice.

PMID- 16092566
TI  - Extraction, bone graft, and immediate placement of a 6-unit fixed bridge.

PMID- 16092568
TI  - Cyber solutions to practice problems.

PMID- 16092569
TI  - After the flood: surviving Hurricane Juan.
AB  - Capital Health is the largest integrated academic health district in Atlantic
      Canada. It provides tertiary health services to Atlantic Canadians and to 40 per
      cent of Nova Scotia's population. Capital Health consists of nine facilities, one
      of which is the Queen Elizabeth II Health Sciences Centre. The QEII is the
      largest adult academic health centre in Atlantic Canada, occupying 10 buildings
      on two sites. It employs 8500 staff and has 1075 beds. The QEII was created in
      1996 with the merger of the Victoria General (VG), Halifax Infirmary (HI), Abbie
      J. Lane Memorial, Camp Hill Veterans' Memorial, Nova Scotia Rehabilitation Centre
      and the Nova Scotia Cancer Centre. There are 33 operating rooms at the HI and VG
      sites; together about 29,000 operations are performed there each year. The two
      hospitals are located about five city blocks away from each other. This article
      discusses how the two facilities coped after the devastation of Hurricane Juan in
      September 2003.

PMID- 16092570
TI  - A night in the life of an OR nurse.
AB  - The author shares a personal experience, during a night shift in the OR, that
      changed her forever. I was defined as a nurse by that moment of trauma. I spent 9
      years as a trauma specialist in a large U.S. hospital. We did gun shots and
      stabbings every single night. After facing the results of too many school
      shootings, I came back to Canada. I was tired. After that night, death was never
      again an idea, a poetic notion of the spirit leaving the body. It was cold, it
      was pulseless, it was bloody, and it has a smell all it's own. To this day I can
      tell if a patient is going to die on the table, I can smell it. I had faced fear
      and death, and survived. I was certainly not "new" anymore... nor was I naive.

PMID- 16092571
TI  - Bullying and harassment in perioperative settings.
AB  - This article explores the concepts of bullying and harassment, defines the terms
      and their implications, and explores similarities and differences between the
      two. It also examines pertinent legislation and identifies strategies to raise
      awareness and optimise a bullying and harassment-free perioperative environment.
      Bullying and harassment in the workplace was the focus of this presentation at
      NATN Congress 2002. Challenging behaviours involving patients and careers is
      another topic in itself.

PMID- 16092572
TI  - Interactive work place trauma (IWPT).
AB  - Tragically, horizontal violence and bullying behaviour being master minded by
      nursing colleagues is firmly entrenched in many perioperative environments--just
      like a serious pathological bacteria. Interactive Workplace Trauma (IWPT) is
      ugly, mean, destructive, demoralizing and counterproductive to efficient,
      effective patient care and positive staff performance. Get educated and use
      astute observations to ensure you clearly understand what is occurring. Make sure
      the staff feel safe and have the appropriate, necessary protection to deal with
      unacceptable conduct. Deal effectively with the bullies. Remember if it is not
      documented, it didn't happen!

PMID- 16092573
TI  - Leadership in health care--orchestrating change.
AB  - Today health care is an orchestra. Patients arrive hours before surgery and leave
      hours afterward. They bring manila folders full of downloaded information and
      question lists. They maneuver themselves through complex systems; they are
      instrumental in coordinating their own needs and care.

PMID- 16092574
TI  - Patients' understanding of and compliance with medications: the sixth vital sign?

PMID- 16092575
TI  - Heparin-induced thrombocytopenia: an iceberg rising.

PMID- 16092576
TI  - Patients' understanding of their treatment plans and diagnosis at discharge.
AB  - OBJECTIVE: To ascertain whether patients at discharge from a municipal teaching
      hospital knew their discharge diagnoses, treatment plan (names and purpose of
      their medications), and common side effects of prescribed medications. PATIENTS
      AND METHODS: From July to October 1999, we surveyed 47 consecutive patients at
      discharge from the medical service of a municipal teaching hospital in New York
      City (Brooklyn, NY). Patients were asked to state either the trade or the generic
      name(s) of their medication(s), their purpose, and the major side effect(s), as
      well as their discharge diagnoses. Patients were excluded if they were not
      oriented to person, place, and time, were unaware of the circumstances
      surrounding their admission to the hospital, and/or did not speak or understand
      English. RESULTS: Of the 47 patients surveyed, 4 were excluded. Of the remaining
      43 patients, 12 (27.9%) were able to list all their medications, 16 (37.2%) were
      able to recount the purpose of all their medications, 6 (14.0%) were able to
      state the common side effect(s) of all their medications, and 18 (41.9%) were
      able to state their diagnosis or diagnoses. The mean number of medications
      prescribed at discharge was 3.89. CONCLUSIONS: Less than half of our study
      patients were able to list their diagnoses, the name(s) of their medication(s),
      their purpose, or the major side effect(s). Lacking awareness of these factors
      affects a patient's ability to comply fully with discharge treatment plans.
      Whether lack of communication between physician and patient is actually the cause
      of patient unawareness of discharge Instructions or if this even affects patient
      outcome requires further study.

PMID- 16092577
TI  - Association of heparin-dependent antibodies and adverse outcomes in hemodialysis
      patients: a population-based study.
AB  - OBJECTIVE: To determine whether some adverse outcomes of hemodialysis could be
      explained by subclinical heparin-induced thrombocytopenia (HIT). PATIENTS AND
      METHODS: Platelet factor 4 (PF4)-heparin antibodies were measured by enzyme
      linked immunosorbent assay In a population-based cohort of hemodlalysis patients.
      Participants were then followed up prospectively for thromboembollc events,
      cardiovascular events, or death. RESULTS: Of the 59 hemodialysis patients
      residing In Olmsted County, Minnesota, 57 (97%) agreed to study participation.
      The mean +/- SD age of the patients was 64 +/- 17 years (median hemodialysis
      duration, 23 months), and 27 (47%) were women. The enzyme-linked Immunosorbent
      assay was positive for PF4-heparin antibodies in 2 patients (3.5%). The PF4
      heparin antibody content varied over a 10-fold range and was not associated with
      the duration of hemodialysis (P = .99). During a median follow-up of 798 days, 16
      thrombotic events, 37 cardiovascular events, and 23 deaths (Including 13
      cardiovascular deaths) occurred. After adjusting for the Framingham risk score,
      the all-cause mortality rate was significantly higher for patients with the
      highest tertile of PF4-heparln antibody content compared with patients in the
      lower tertilles (hazard ratio, 2.47; P = .03). Furthermore, 8 (73%) of deaths in
      this tertile were due to cardiovascular causes (hazard ratio, 4.14; P = .02).
      CONCLUSIONS: Despite repetitive heparin exposure, the prevalence of HIT In
      patients undergoing maintenance hemodialysis is no greater than that anticipated
      for other patient populations. However, to our knowledge, this is the first study
      to show an association between elevated PF4-heparin antibodies and Increased
      mortality rates in hemodlalysis patients.

PMID- 16092578
TI  - Outcomes among valvular heart disease patients experiencing ischemic stroke or
      transient ischemic attack in Olmsted County, Minnesota.
AB  - OBJECTIVE: To estimate the rates and predictors of survival and recurrence among
      residents of Olmsted County, Minnesota, who received an Initial diagnosis based
      on 2-dimensional color Doppler echocardiography of moderate or severe mitral or
      aortic stenosis or regurgitation and who experienced a first ischemic stroke,
      transient ischemic attack (TIA), or amaurosis fugax. PATIENTS AND METHODS: At the
      Mayo Clinic in Rochester, Minn, we used the resources of the Rochester
      Epidemiology Project to identify Individuals who met the criteria for inclusion
      in the study and to verify exclusion criteria. The study included all residents
      of Olmsted County, Minnesota, who experienced a first Ischemic stroke, TIA, or
      amaurosis fugax within 30 days of or subsequent to receiving a first-time 2
      dimensional color Doppler echocardlography-based diagnosis of moderate or severe
      mitral or aortic stenosis or regurgitation between January 1, 1985, and December
      31, 1992. The Kaplan-Meier product-limit method was used to estimate the rates of
      subsequent stroke and death after the ischemic stroke, TIA, or amaurosis fugax.
      The Cox proportional hazards model was used to assess the effect of several
      potential risk factors on subsequent stroke occurrence and death. RESULTS: For
      the 125 patients in the study, the Kaplan-Meier estimates of the risk of death
      and the risk of stroke at 2-year follow-up were 38.6% (95% confidence interval
      [CI], 29.9%-47.5%) and 18.5% (95% CI, 10.0%-27.0%), respectively. Compared with
      the general population, death rates were significantly Increased (standardized
      mortality ratio = 1.75; 95% CI, 1.38-2.19; P < .001) but rates of subsequent
      stroke occurrence were not (standardized morbidity ratio = 1.20; 95% CI, 0.75
      1.84; P = .40). After adjustment for age, sex, and cardiac comorbidity, neither
      the type nor severity of valvular heart disease was an independent determinant of
      survival or subsequent stroke occurrence. CONCLUSIONS: Patients with mitral or
      aortic valvular heart disease who experience Ischemic stroke, TIA, or amaurosis
      fugax have Increased rates of death, but not recurrent stroke, compared with
      expected rates. Other cardiovascular risk factors are more important determinants
      of survival In these patients than the type or echocardiographic severity of the
      valvular heart disease.

PMID- 16092579
TI  - Infectious complications of percutaneous vascular closure devices.
AB  - OBJECTIVE: To describe the infectious complications of percutaneous vascular
      closure devices (PVCDs) on the basis of our institutional experience with PVCDs
      and the published medical literature. PATIENTS AND METHODS: We retrospectively
      reviewed all cases of PVCD-related Infection seen at the Mayo Clinic in
      Rochester, Minn, between January 1, 2000, and December 31, 2003, and searched the
      English language medical literature for all previously published reports.
      RESULTS: We identified 46 cases in the medical literature and 6 cases from our
      Institutional database. The median age of patients was 63 years (range, 40-79
      years). Diabetes mellitus and obesity were the most common comorbidities. The
      median Incubation period from device Insertion to presentation with access-site
      infection was 8 days (range, 2-29 days). The most common presenting symptoms were
      pain, erythema, fever, swelling, and purulent drainage at the access site.
      Mycotic pseudoaneurysm (22 cases) was the most common complication.
      Staphylococcus aureus was responsible for most (75%) of the Infections. All
      patients underwent surgical debridement, and 54% required reconstructive
      procedures. The median duration of antibiotic treatment was 28 days (range, 7-42
      days). The mortality rate was 6% (3 patients). CONCLUSIONS: Infection associated
      with PVCD placement is uncommon but is an extremely serious complication.
      Morbidity is high, and aggressive medical and surgical interventions are required
      to achieve cure.

PMID- 16092580
TI  - Valvular heart disease in patients taking pergolide.
AB  - OBJECTIVE: To Investigate the frequency of valvular heart disease in patients
      taking pergolide. PATIENTS AND METHODS: The medical records of patients seen at
      the Mayo Clinic in Jacksonville, Fla, between 1998 and 2003 were searched
      electronically for the word pergolide and the presence of a 2-dimensional
      echocardiogram. Patients who had not taken pergolide before undergoing
      echocardlography served as the control group. Echocardiograms were reviewed for
      the presence of valvular regurgitation. The frequency of valvular disease in
      patients taking pergolide was calculated and compared with controls. Associations
      with dosage and years of treatment also were examined. RESULTS: Fifty-five
      patients made up the pergolide group, and 63 served as controls. When looking at
      aortic regurgitation (AR) of any degree, 45% of patients in the pergolide group
      had AR, compared with 21% of controls (P = .006). The frequency of moderate to
      severe valvular regurgitation in the pergolide group was 11% (95% confidence
      interval [CI], 4%-22%), 13% (95% CI, 5%-24%), and 13% (95% CI, 5%-24%) for the
      tricuspid, mitral, and aortic valves, respectively. No statistical difference was
      identified in the frequency of moderate to severe valvular regurgitation (mitral,
      tricuspid, or aortic) when compared with controls. There was marginal evidence of
      an association between a higher daily dosage of pergolide and moderate to severe
      AR (P = .05). CONCLUSION: The frequency of AR appears to be Increased in patients
      taking pergolide. Our study suggests that if a cause-effect relationship exists
      between pergolide and valvular heart disease, it likely occurs at a low but
      clinically important Incidence and may be associated with dosage.

PMID- 16092581
TI  - Effects of biochemically confirmed smoking cessation on white blood cell count.
AB  - OBJECTIVES: To determine the relationship between white blood cell (WBC) Indices
      and several baseline variables In a large cohort of healthy smokers and to assess
      whether these changed after biochemically confirmed smoking cessation. SUBJECTS
      AND METHODS: The study consisted of 784 healthy smokers enrolled in a trial of
      sustained-release bupropion, 300 mg/d, for relapse prevention after smoking
      cessation from 1995 to 1998. Both WBC counts and absolute neutrophil counts
      (ANCs) were measured at baseline, week 7, and week 52. Smoking status was
      assessed at weeks 7 and 52 by self-report and biochemically confirmed with
      expired air carbon monoxide levels. Multivariate analyses compared changes in WBC
      count and ANC between smokers who did and did not stop smoking, adjusting for
      treatment group, age, sex, and body mass index. RESULTS: Of 784 smokers enrolled,
      461 had biochemically confirmed tobacco abstinence after 7 weeks of bupropion;
      429 were randomly assigned to receive continued bupropion therapy or placebo
      until week 52. Between baseline and week 7, there was a significantly larger
      decrease in WBC count in continuously abstinent subjects compared with continuing
      smokers (adjusted P = .03). At 52 weeks, continuously abstinent subjects,
      compared with continuing smokers, had a greater decline from baseline in WBC
      count (1.2 +/- 1.9 x 10(9)/L vs 0.1 +/- 1.9 x 10(9)/L; P < .001) and ANC (1.0 +/-
      1.6 x 10(9)/L vs 0.2 +/- 1.5 x 10(9)/L; P < .001). CONCLUSION: Biochemically
      confirmed tobacco abstinence leads to a rapid and sustained decrease in WBC and
      ANC, possibly reflecting a decrease In an underlying state of tobacco-induced
      inflammation.

PMID- 16092582
TI  - B-type natriuretic peptide as a biomarker beyond heart failure: speculations and
      opportunities.
AB  - Cardiac secretion of B-type natriuretic peptide (BNP) Increases with the
      progression of heart failure (HF), and plasma measurement of BNP has emerged
      recently as a useful, cost-effective biomarker for the diagnosis and prognosis of
      HF. The diagnostic utility of BNP is complemented by its therapeutic use in
      decompensated HF. Although clinical use of BNP as a biomarker in HF is
      Increasing, the specificity of BNP for HF is not robust, suggesting that other
      mechanisms beyond simple ventricular stretch stimulate BNP release. Several
      studies have shown that BNP levels Increase in other cardiovascular disease
      states including ischemia, arrhythmias, fibrosis, cardiac hypertrophy, and
      coronary endothelial dysfunction. Furthermore, 2 important studies revealed
      recently that moderate elevations In BNP level, well below the HF range, have
      prognostic value for future cardiovascular events. Specifically, BNP levels
      greater than 20 pg/mL were associated with significantly Increased risk of HF and
      atrial fibrillation. These observations increase speculation that elevated BNP
      levels represent a final common pathway for many cardiovascular pathologic states
      and that BNP can be used as a biomarker for non-HF mechanisms, preclinical
      disease, and other pathologic states of myocardial disease.

PMID- 16092583
TI  - Clinical diagnosis of prolonged states of impaired consciousness in adults.
AB  - A prolonged state of impaired consciousness is a devastating consequence of
      severe structural brain injury but fortunately is uncommon. Patients may be
      diagnosed as being in a persistent vegetative state, having akinetic mutism, or
      being in a minimally conscious state. These conditions can be distinguished from
      each other by a comprehensive clinical neurologic examination. Recovery is
      determined by age, cause, and time in such state. For patients diagnosed as being
      in a permanent (irreversible) vegetative state, hope for a clinically meaningful
      recovery is unrealistic after 1 year. Prolonged survival is possible only with
      meticulous care and aggressive medical intervention to prevent and treat systemic
      complications.

PMID- 16092584
TI  - Medication-induced hyperprolactinemia.
AB  - Medication use is a common cause of hyperprolactinemia, and it is important to
      differentiate this cause from pathologic causes, such as prolactinomas. To
      ascertain the frequency of this clinical problem and to develop treatment
      guidelines, the medical literature was searched by using PubMed and the reference
      lists of other articles dealing with hyperprolactinemia due to specific types of
      medications. The medications that most commonly cause hyperprolactinemia are
      antipsychotic agents; however, some newer atypical antipsychotics do not cause
      this condition. Other classes of medications that cause hyperprolactinemia
      include antidepressants, antihypertensive agents, and drugs that increase bowel
      motility. Hyperprolactinemia caused by medications is commonly symptomatic,
      causing galactorrhea, menstrual disturbance, and impotence. It is Important to
      ensure that hyperprolactinemia in an Individual patient is due to medication and
      not to a structural lesion in the hypothalamic/pituitary area; this can be
      accomplished by (1) stopping the medication temporarily to determine whether
      prolactin levels return to normal, (2) switching to a medication that does not
      cause hyperprolactinemia (in consultation with the patient's psychiatrist for
      psychoactive medications), or (3) performing magnetic resonance imaging or
      computed tomography of the hypothalamic/pituitary area. If the patient's
      hyperprolactinemia is symptomatic, treatment strategies include switching to an
      alternative medication that does not cause hyperprolactinemia, using estrogen or
      testosterone replacement, or, rarely, cautiously adding a dopamine agonist.

PMID- 16092585
TI  - Fasten your seat belts.

PMID- 16092586
TI  - Screening for cervical cancer and initial treatment of patients with abnormal
      results from papanicolaou testing.
AB  - New techniques for cervical cancer screening and a better understanding of the
      natural history of human papillomavirus (HPV) and cervical neoplasia have
      inspired a quest for more rational screening strategies for cervical cancer.
      Often, screening intervals for women older than 30 years can be expanded safely
      to every 3 years, and experts now agree that screening may cease after
      hysterectomy and in elderly women (provided certain criteria have been met).
      Liquid-based cytology produces more satisfactory specimens than conventional
      testing and offers the valuable option of treating atypical squamous cells of
      undetermined significance by "reflex" testing for high-risk types of HPV on the
      original specimen. Testing for HPV as an adjunct to cervical cytology for primary
      screening is now considered reasonable for many women older than 30 years.

PMID- 16092587
TI  - 68-year-old man with fever, back pain, and mental status changes.

PMID- 16092588
TI  - Survival of a neurologically intact patient with subarachnoid hemorrhage and
      cardiopulmonary arrest.
AB  - Subarachnold hemorrhage (SAH) is a relatively common cause of cardiopulmonary
      arrest (CPA). Long-term survival with SAH and CPA is rare, and the vast majority
      of those who survive have moderate to severe neurologic disability. To our
      knowledge, there are no prior reports of patients with SAH who experience CPA and
      survive without neurologic deficit. We describe a patient with SAH who
      experienced CPA shortly after hospital admission and survived without neurologic
      sequelae (Cerebral Performance Category 1). Prompt defibrillation of SAH-induced
      ventricular fibrillation and timely neurologic intervention are essential for
      good neurologic outcome.

PMID- 16092589
TI  - Atypical presentation of eosinophilic endomyocardial disease.
AB  - Idiopathic hypereosinophllic syndrome is classically defined as prolonged,
      unexplained peripheral eosinophilia in a patient presenting with evidence of end
      organ damage. The heart is frequently Involved, resulting In eosinophilic
      endomyocardial disease and eventually restrictive cardlomyopathy. The mortality
      rate is high because of progressive heart failure or ventricular arrhythmias. We
      describe a patient who presented with a left ventricular apical thrombus without
      notable peripheral eosinophilia. Findings from clinical evaluation and extensive
      diagnostic testing, including right ventricular biopsy, were Inconclusive.
      Resection of the thrombus and subjacent endomyocardium revealed eosinophilic
      Infiltration of the endomyocardium, which led to the diagnosis of eosinophilic
      endomyocardial disease. Clinicians should be aware of the variable presentation
      of patients with eosinophil-associated endomyocardial disease so that affected
      patients may benefit from early diagnosis and treatment.

PMID- 16092590
TI  - Introduction to a cancer symposium for the practitioner.

PMID- 16092591
TI  - Non-Hodgkin lymphoma: diagnosis and treatment.
AB  - Non-Hodgkin lymphomas are a heterogeneous group of malignancies of the lymphoid
      system. Based on the World Health Organization classification of hematological
      and lymphoid tumors, these diseases have been classified as B-cell and T-cell
      neoplasms. B-cell lymphomas account for approximately 90% of all lymphomas, and
      the 2 most common histological disease entities are follicular lymphoma and
      diffuse large B-cell lymphoma. Approximately 55,000 to 60,000 new cases of non
      Hodgkin lymphoma are diagnosed annually in the United States, a number that has
      nearly doubled during the past 3 decades. The Ann Arbor Staging Classification is
      used routinely to classify the extent of disease, and the International
      Prognostic Index has been used to define prognostic subgroups. Also, recent data
      have identified molecular and genetic markers of prognosis that may be used in
      the future to further refine treatment decisions. Treatment of these diseases is
      based on the histology and extent of disease. Patients with follicular lymphomas
      with early-stage disease generally are treated with radiation therapy, whereas
      those with stage III and IV disease requiring treatment usually are treated with
      chemotherapy, Immunotherapy, or radioimmunotherapy. These patients generally
      experience long survival, but only a minority are cured. For patients with
      diffuse large B-cell lymphoma, treatment of limited-stage disease generally
      includes doxorubicin-based chemotherapy combined with rituximab followed by
      involved field radiation therapy. Those with extensive disease are treated with
      rituximab combined with chemotherapy alone. Disease relapse is a problem, and
      high-dose therapy with stem cell support is the treatment of choice for
      chemosensitive relapsed aggressive lymphomas. Patients with chemoresistant
      disease or whose disease relapses subsequently should be treated with novel
      experimental therapies.

PMID- 16092592
TI  - Retrograde jejunojejunal intussusception secondary to metastatic melanoma.

PMID- 16092593
TI  - PSA and clinical responses to celecoxib in a patient with prostate cancer and
      bone metastases.

PMID- 16092594
TI  - Postural and venous stasis-induced changes in total calcium.

PMID- 16092595
TI  - Workplace hazard reduction through ergonomic evaluation.

PMID- 16092596
TI  - Progress for palliative medicine as a subspecialty.

PMID- 16092597
TI  - Neuromuscular complications of cancer diagnosis and treatment.
AB  - Neuromuscular disorders are a common cause of morbidity in patients with cancer.
      They can be a direct effect of the primary malignancy, a paraneoplastic effect,
      or a treatment complication. Malignant neoplasms may infiltrate or compress nerve
      roots, plexi, and peripheral nerves, causing various sensory and motor symptoms.
      Electrodiagnostic testing, cerebrospinal fluid analysis, and neuroimaging are
      helpful in confirming the diagnosis. Treatment for neuropathies of neoplastic
      origin involves irradiation and chemotherapy, which may improve pain, but usually
      does not improve neurologic function. Paraneoplastic syndromes are rare and
      sometimes result from production of autoantibodies directed against neural
      antigens present in tumor tissues. They commonly precede any symptoms related to
      the cancer itself, and discovery of such syndromes necessitates a thorough
      investigation to look for an occult neoplasm. Treatment of the underlying cancer
      occasionally improves neurologic function. Both brachial and lumbosacral
      plexopathies may represent a complication of radiotherapy. Electrodiagnostic
      tests particularly are helpful; these diagnostics demonstrate the presence of
      myokymic discharges, which are suggestive of radiation injury. Many
      chemotherapeutic agents may cause peripheral neurotoxicity and associated acute
      and chronic peripheral neuropathies, particularly if given to patients with
      preexisting hereditary or acquired neuropathies. These side effects are a
      limiting factor in cancer treatment. Other potential neuromuscular problems
      related to cancer include side effects of steroids and other immunosuppressants,
      effects secondary to bone marrow transplantation, and infections. Early
      recognition and management of these disorders will improve patient outcome and
      quality of life.

PMID- 16092598
TI  - The difficulties of diagnosing neuromuscular complications.

PMID- 16092599
TI  - Paraneoplastic syndromes and the nervous system.

PMID- 16092600
TI  - Newer treatments for fungal infections.
AB  - Invasive fungal infections are a significant cause of morbidity and mortality
      among immunocompromised cancer patients, and until recently, treatment options
      have been limited. The poor outcomes of these infections, and the increased
      incidence of disease, particularly due to resistant and less common fungal
      isolates, necessitate the development of new agents. Antifungal drug development
      had been a slow process since the release of amphotericin B over 40 years ago.
      However, since 1995, six new systemic antifungals have been approved: three lipid
      formulations of amphotericin B, the initial second-generation triazole, and the
      first two approved agents in a new class of antifungals with a novel mechanism of
      action, the echinocandins. These newer agents, and several others currently in
      development, offer improved tolerability and safety profiles and extend the
      spectrum of coverage to resistant and less-common fungal infections. The authors
      describe each of these new compounds and discuss how they fit into the overall
      management of fungal infections in patients with cancer.

PMID- 16092601
TI  - Hope for patients with neoplastic disease and invasive fungal infections.

PMID- 16092602
TI  - Suspected spinal cord compression in cancer patients: a multidisciplinary risk
      assessment.
AB  - Investigators involved in this study sought to identify independent clinical
      predictors of spinal cord compression (SCC) in cancer patients by analyzing a
      comprehensive set of potential risk factors based on the results of spine
      magnetic resonance imaging (MRI). In all, the investigators analyzed 136 episodes
      of suspected SCC among 134 cancer patients evaluated with spine MRI. Each subject
      was interviewed within 7 days of the spine MRI to collect accurate self-reported
      symptom data. Neurologic examination data were detailed by the physician
      examining the subject prior to the spine MRI; uniform demographic and clinical
      information regarding the subject's cancer history was abstracted from the
      medical record. Multivariable logistic regression analysis was used to identify
      independent predictors of SCC. Clinically significant SCC was defined as thecal
      sac compression (TSC), which occurred in 50 episodes (37%). Four independent
      predictors of TSC were identified and included information from the neurologic
      examination (abnormal neurologic examination), subject-reported symptoms (middle
      or upper back pain), and the oncologic history (known vertebral metastases and
      metastatic disease at initial diagnosis). These four predictors stratified
      patients experiencing episodes into subgroups with varying risks of TSC, ranging
      from 8% (no risk factors) to 81% (three or four risk factors). These results
      confirmed earlier retrospective studies indicating that the evaluation of cancer
      patients with suspected SCC should be based upon clinical information that
      includes cancer-related history, symptom data,and the presence of pertinent
      neurologic signs. These predictors may help clinicians to assess risk in this
      patient population.

PMID- 16092603
TI  - Medroxyprogesterone acetate better than venlafaxine at relieving hot flashes.

PMID- 16092604
TI  - The financial benefits of acute inpatient palliative medicine: an inter
      institutional comparative analysis by all patient refined-diagnosis related group
      and case mix index.
AB  - Financial comparisons of acute care hospital services are possible using the
      Centers for Medicare & Medicaid Services case mix index (CMI) and All Patient
      Refined-Diagnosis Related Group (APR-DRG) data. We compared The Cleveland
      Clinic's Inpatient Palliative Medicine (CCIPM) acute care unit's CMI and APR-DRG
      data with national and peer institution data. Total mean charges per admission to
      the CCIPM unit were 7,800 dollars lower than at other peer institutions despite
      an equivalent severity of illness and longer length of stay and higher mortality
      in the CCIPM unit. The lower charges were due primarily to lower laboratory and
      pharmaceutical charges. We conclude that an acute inpatient palliative medicine
      unit operating within a comprehensive integrated palliative medicine program is
      cost-effective in providing specialized care for people with advanced disease.

PMID- 16092605
TI  - Cancer patients, opioids, and driving.

PMID- 16092606
TI  - Establishment of general dental practice in the National Health Service.

PMID- 16092607
TI  - William J. Morrison (1860-1926): co-inventor of the cotton candy machine.
AB  - William James Morrison (1860-1926), from Nashville, Tennessee was a noted
      dentist, lawyer, author and leader in civic and political affairs. An 1890
      graduate of the University of Tennessee Dental College, Dr. Morrison became
      President of the Tennessee State Dental Association in 1894. He had a wide
      interest in both science and politics, and was personally associated with both
      William Jennings Bryan and President Woodrow Wilson. Additionally, he was a
      popular author of children's books and particularly effective in fostering
      reading among youngsters. Also, Dr. Morrison patented several important
      inventions. He developed a process for extracting oils from cotton seed, and
      converting them into a lard substitute. Likewise, he devised a chemical process
      to purify the public drinking water for Nashville. In 1897, he and John C.
      Wharton (a fellow Nashville candy maker) conceived and co-patented an "electric
      candy machine" which produced cotton candy (then called "Fairy Floss".) This
      article provides background information about the production of spun sugar during
      medieval times and later, it describes the development of their cotton candy
      machine, the process of its operation and details about its eventual worldwide
      commercialization. In addition, it discusses the introduction of this new
      confection to the public, during the 184 day, Louisiana Purchase Exposition, held
      in St. Louis, MO. in 1904. In late 1926, Dr. Morrison, died of a stroke at age
      66.

PMID- 16092608
TI  - Gleanings about dentistry from the world of literature (thirty-six in a series).

PMID- 16092609
TI  - Significant events in the history of operative dentistry.

PMID- 16092610
TI  - Dentistry on stamps. The narwhal.

PMID- 16092611
TI  - A new theory: electricity as a cause of caries!

PMID- 16092612
TI  - New research looks at ergonomic stresses on operating room staff.

PMID- 16092613
TI  - Will you be ready for JCAHO's unannounced surveys in 2006?

PMID- 16092614
TI  - Link seen between OR schedule, safety.

PMID- 16092615
TI  - ORB Collaborative to track OR performance.

PMID- 16092616
TI  - Labeling meds is 2006 JCAHO goal.

PMID- 16092617
TI  - Time to retool as CABG volume shrinks.

PMID- 16092618
TI  - Uniform preop review for high-risk patients.

PMID- 16092619
TI  - Managers discuss OR finance, patient flow.

PMID- 16092620
TI  - If OSHA knocks, will you be prepared?

PMID- 16092622
TI  - Muscular dystrophies.

PMID- 16092621
TI  - Preadmit nurse avoids rushed assessments.

PMID- 16092623
TI  - Muscular dystrophies.
AB  - The rapid technological advances in this new millennium have brought about a
      broadened concept of the definition of MD, improved medical care, and the
      prospect of a definitive cure with gene therapy. While we await a cure,
      aggressive supportive treatment by an integrative team of health care providers
      is the key to improving quality and length of life of patients with MD.

PMID- 16092624
TI  - A newborn with intestinal obstruction.

PMID- 16092625
TI  - A 4-year-old boy with fever. Achondroplasia.

PMID- 16092626
TI  - The diagnosis of muscular dystrophy.
AB  - Pediatricians should be familiar with the common presenting signs and symptoms of
      MD so that they can make a clinical diagnosis of possible MD based on the
      patient's medical history, a physical examination, and a CK screen. Appropriate
      referral to a neuromuscular specialist will then enable the precise diagnosis of
      MD to be made with definitive histologic, biochemical, and genetic testing.

PMID- 16092627
TI  - The heart in muscular dystrophy.
AB  - Pediatricians and other healthcare professionals need to be alert to the presence
      and progression of cardiac involvement in patients with MD. The signs and
      symptoms of cardiac involvement may be minimal, necessitating careful interval
      history, physical examination, and noninvasive cardiac testing. Available
      treatment strategies may reduce disease morbidity and mortality. It is reasonable
      to expect that a child who has skeletal muscle weakness from MD may have cardiac
      involvement, even if it is subclinical. Treatment of the muscular dystrophies
      through genetic engineering is a future dream. However, the improvements in
      clinical care, evaluation and treatment standards, and multidisciplinary
      supportive care are able to benefit the current generation of children.

PMID- 16092628
TI  - Pulmonary management of the patient with muscular dystrophy.
AB  - Pulmonary involvement is common in patients with muscular dystrophy, and routine
      screening for evidence of respiratory muscle dysfunction should be performed.
      Testing for respiratory muscle strength, as well as an assessment for sleep
      disordered breathing, should be obtained in consultation with a specialist.
      Adequate airway clearance and correction of impaired ventilation are the key
      components of pulmonary management in this group of patients. Also, special
      emphasis on airway clearance is recommended during upper respiratory infections,
      as well as in the postoperative period. Early initiation of ventilatory support
      has been shown to result in longer life expectancy.

PMID- 16092629
TI  - Developing an interdisciplinary palliative care plan for the patient with
      muscular dystrophy.
AB  - The care of children with MD presents many complex issues. An interdisciplinary
      team, focused on patient and family outcome, that incorporates palliative care
      initiatives can best outline and meet the goals of family-centered care. The
      early introduction of a palliative team allows for a relationship of trust to
      develop, serving as the foundation for the many interventions necessary to fill
      the gaps in care that arise during the care of a child with a chronic, life
      threatening illness such as MD.

PMID- 16092630
TI  - Congenital muscular dystrophy.

PMID- 16092631
TI  - Limb-girdle muscular dystrophy in childhood.
AB  - LGMD refers to a class of muscular dystrophies with onset in the proximal
      muscles. They are genetically heterogeneous, with both autosomal recessive and
      dominant forms. The autosomal recessive forms are more common and in general
      follow a more severe course compared to the dominant forms. It is important to
      reach a specific genetic diagnosis beyond making a group diagnosis of LGMD to
      provide adequate genetic counseling, to predict risks for the patient such as the
      development of cardiomyopathy, and to be able to take advantage of specific
      treatments when they become available. Establishing a specific diagnosis requires
      knowledge about the individual clinical features, expert analysis of the muscule
      biopsy, and the guided initiation of appropriate genetic testing.

PMID- 16092632
TI  - Manufacturing's prescription for improving healthcare quality.
AB  - In this article, the author provides an account of the benefits of using
      Statistical Process Control and Six Sigma to measure and improve healthcare
      quality. Through data analysis, the process variations that diminish quality can
      be evaluated and minimized. W. Edwards Deming's management theory taught that
      variation reduction enabled continuous improvement and that statistical methods
      were the key to achieving this. Although the methodology was created for the
      manufacturing environment, service industry professionals have discovered its
      value for objective, data-driven decision making.

PMID- 16092633
TI  - Compensating medical injury victims in the United States: there must be a better
      way.
AB  - The crisis of medical malpractice insurance affordability and availability,
      highlighted by significant annual premium increases in many states, has led many
      observers to question the adequacy of state civil justice systems for
      compensating medical injury victims. Evidence exists that (a) many victims of
      medical injury are not compensated, (b) the state civil litigation systems
      present formidable obstacles to many injury victims seeking compensation, (c)
      many legitimate claimants may not be able to secure legal representation for
      their cases, and (d) the chance of recovery and the amount of damages awarded
      depend on the state in which the plaintiff resides.

PMID- 16092634
TI  - The need for time management training is universal: evidence from Turkey.
AB  - In many developing countries, healthcare administrators are currently facing
      challenges that are representative of those in the United States. Most healthcare
      administrators here are physicians with no formal training in healthcare
      administration, and this is perhaps most apparent in their difficulties with time
      management. The authors' purpose in this study was to characterize the time
      management difficulties of administrators working in primary healthcare
      facilities of the Ministry of Healthcare. In the study, 67 healthcare
      administrators each completed a 31-item time management questionnaire. Of the
      participants, 79.1% reported that they have never attended time management
      courses or workshops. Although 76.1% said they were free to choose the priority
      of their daily tasks, only 44.8% felt they knew how much time they should allow
      for each activity in their daily life. These and other findings in the study
      suggest that the need for time management education is a well-defined target for
      intervention, both in university-based programs for future healthcare
      administrators and in workplace-based programs, such as in-service training for
      healthcare administrators who are already working.

PMID- 16092635
TI  - Improving patient care through patient-family education programs.
AB  - The author's purpose of this study was to investigate patients' beliefs about the
      effectiveness of a patient education program. The authors interviewed general
      medicine and cardiac patients and their families at a large teaching hospital.
      They asked participants to describe the kind of information the hospital provided
      about patients' illnesses, pain management, and self-care following discharge and
      asked participants if they were satisfied with the information provided. The
      findings revealed that cardiac patients had greater access to information about
      their illnesses than general medicine patients. Overall, patients received verbal
      communication from doctors and nurses about their condition. All of the patients
      relied on pharmacological interventions for managing their pain and were unclear
      about how to manage their care following discharge. The authors describe
      recommendations for developing a written patient education curriculum, including
      information that addresses pain management options and discharge protocols.

PMID- 16092636
TI  - A 2004 retrospective; a 2005 prospective.

PMID- 16092637
TI  - Quality of life issues and assessment tools as they relate to patients with
      chronic nonmalignant pain.

PMID- 16092638
TI  - Synergistic interaction of epinephrine and calcium ionophore in platelet
      aggregation.
AB  - BACKGROUND: Platelets play a key role in haemostasis. Human Platelets contain
      alpha2 adrenergic receptors, which are coupled with guanine nucleotide proteins
      (G proteins). The platelet activation involves a number of receptors for
      agonists. It has also been shown that most of the agonists act in synergy and
      potentiate the effects of each other. The present experimental study was designed
      to study the potentiation of epinephrine on human platelets by calcium ionophore
      A23187 and the possible role of calcium in platelet aggregation as a second
      messenger. METHODS: Study was carried out at Department of Biological Sciences
      Aga Khan University, Karachi. Blood samples from healthy volunteers were
      collected; Platelet aggregation was measured using Dual channel Lumi
      Aggregometer. The chemicals used include epinephrine, calcium ionophore A23187,
      yohimbine, diltiazem, verapamil and S Nitrosoacetylpenicillamin (SNAP). RESULTS:
      Epinephrine at low concentrations (0.01-0.2 microM) and/or A23187 (0.1-0.5
      microM) itself did not produce platelet aggregation. However, when added
      together, a marked potentiation of platelet aggregation was observed. This
      synergistic effect was inhibited by alpha2-receptor blocker yohimbine; (IC50 =
      0.05 microM) showing that the response is receptor mediated. To find out the
      molecular basis of this potentiation, we used SNAP, a nitric oxide donor and Ca++
      channel blockers, i.e. diltiazem and verapamil. The SNAP, diltiazem and verapamil
      inhibited the platelet aggregation induced by A23187 and epinephrine with IC50
      value of 0.5 microM, 50 microM and 22 microM respectively. CONCLUSION: The
      results of the study suggest that epinephrine and calcium ionophore act
      synergistically and Ca++ plays an important role in this synergistic interaction.
      While calcium channels blocking drugs diltiazem and verapamil inhibit this
      synergism.

PMID- 16092639
TI  - Comparison of Mantoux's test with diagnostic BCG in pediatric patients with
      pulmonary tuberculosis.
AB  - BACKGROUND: Pulmonary tuberculosis is a common problem in all age groups in our
      country. Different tests are performed for diagnosis of this disease. This study
      was carried out with an objective to compare Mantoux's test with diagnostic BCG
      in pediatric patients known to have pulmonary tuberculosis. METHODS: This study
      was conducted on one hundred children of either sex, age up to 15 years,
      suffering from pulmonary tuberculosis. Mantoux's test and diagnostic BCG test
      were carried out on each patient simultaneously. Response of the patient to each
      test was recorded on a proforma. Both the tests were compared regarding their
      positivity. RESULTS: Both Mantoux's and BCG tests were found negative in about
      26% cases, and positive in about 40% cases. BCG alone was positive in 34% cases
      in which Mantoux's test was negative. CONCLUSION: It is concluded that in
      paediatric age group, diagnostic BCG test has a definite edge over Mantoux's test
      in diagnosis of tuberculosis.

PMID- 16092640
TI  - Occupational injuries in welders--results from a six month follow-up study.
AB  - BACKGROUND: Injuries are an under recognized public health problem globally. We
      assessed the number and type of occupational injuries in welders, in a
      prospective manner. METHODS: A cohort of 208 welders was re-interviewed twice at
      three-month intervals to determine the type and frequency of injuries in the
      welders primarily involved in the automobile sector, in the twin cities of
      Islamabad and Rawalpindi in Pakistan. Data was analyzed for frequencies and
      counts with STATA 8. RESULTS: Cumulatively, 105 injuries were reported by 61
      welders in the two follow-ups, who took 28 days off as a result of these
      injuries, in the past six months. Four welders reported multiple injuries
      involving the same injury episode. None of the welders reported any permanent
      disfigurement as a result of these injuries. CONCLUSION: Occupational injuries
      are common in the welders working primarily in the automobile sector in the twin
      cities of Islamabad and Rawalpindi. Foreign bodies in the eyes are the most
      common type of injuries sustained by these welders.

PMID- 16092641
TI  - Life style related risk factors for cardiovascular disease among patients at a
      teaching hospital in Karachi.
AB  - BACKGROUND: Cardiovascular disease is a leading cause for morbidity and mortality
      all over the world. It is important to study life style related, modifiable
      cardiovascular risk factors among patients, in order to devise preventive
      strategies. METHODS: We surveyed family practice patients visiting the out
      patient clinics of Aga Khan University Hospital, Karachi. The interview was
      questionnaire-based and recorded the demographic profile of the patients, in
      addition to information on life style related cardiovascular risk factors. The
      ethical requirements for the study were met. SPSS computer software was used for
      data management. RESULTS: Fifty patients were surveyed and included 28 (56%) men
      and 22 (44%) women. Thirty seven (74%) respondents were married, nineteen (38%)
      had graduate education, twenty five (50%) were in private service, and twelve
      (24%) were housewives. Twenty six (52%) respondents were overweight or obese.
      Butter, cream, margarine and red meat was consumed by 17 (34%) and 32 (64%)
      respondents respectively. White meat, fresh fruits and vegetables were consumed
      by 30 (60%), 29 (58%) and 38 (76%) respondents respectively. Oil from vegetable
      sources was used by 49 (98%) respondents. Addition of table salt was found
      occasionally and always in 18 (36%) and 09 (18%) respondents respectively. Twenty
      seven (54%) respondents exercised at least twenty minutes, three times a week,
      while eleven (22%) were current smokers. CONCLUSIONS: Life style related
      modifiable risk factors are prevalent in patients reporting to our hospital. This
      offers an opportunity for preventive strategies, to prevent cardiovascular
      disease. Such surveys, followed by interventional strategies, are recommended to
      be followed by all Primary care facilities.

PMID- 16092642
TI  - Differences between male and female students in cardiovascular and endocrine
      responses to examination stress.
AB  - BACKGROUND: It is known that stress alters biological processes. The aim of the
      present study was to examine the effect of examination stress in young adult male
      and female students. METHODS: Examination stress was studied in 28 young female
      and 21 young male volunteer students of Rafsanjan university of medical Sciences,
      0.5 hour before Physiology examination (stress condition) at 10-12 a.m. and 45
      days after examination (control condition) at the same time in the year 2003.
      RESULTS: There were no differences in BMI of male and female groups at control
      and stress conditions. Subsequent analysis between two sexes showed that males
      had significantly higher systolic [SBP (124.7+/-4.01 mmHg)] and diastolic blood
      pressure [DBP (76.56+/-2.48 mmHg)], heart rate [HR (84.6+/-2.63)] increases in
      stress condition, in both sexes, but in males the increasing of HR is more than
      females, whereas females had higher respiratory frequency increase in stress
      condition, compared to males. Moreover, there were no differences in SBP, DBP and
      HR responses to stress condition in different phases of the menstrual cycle. The
      increased amount of the plasma cortisol in stress condition was significantly
      higher in males (485.3+/-37.9 in stress vs. 335.7+/-27.9 pg/ml in control) than
      females, stress also reduced females' ACTH in both phases of the menstrual cycle
      (13.3+/-0.8 in stress vs. 27.47+/-7.25 pg/ml in control), but in males stress
      increased ACTH (43.72+/-4.45 in stress vs. 49.29+/-3.25 pg/ml in control). In
      males, stress induced a significant decrease in plasma testosterone. Plasma
      progesterone in response to stress showed a significant decrease in the luteal
      phase. CONCLUSION: These data suggest that, the responses to physiology
      examination stress are different between two sexes.

PMID- 16092643
TI  - Frequency and treatment of urinary tract infection in children subjected to urine
      culture, in Sana'a, Yemen.
AB  - BACKGROUND: This study was carried out to estimate the frequency of urinary tract
      infection among children subjected to urine culture presenting to Sam Hospital,
      Sana'a city, Yemen and to determine the susceptibility of the isolated bacteria
      to the antibiotics. METHODS: Record-based study was done in Sam hospital in
      Sana'a city Yemen during three years 1/1/1999-31/12/2001. Out of 70,500 patients
      seen for different causes through that period 820 (1.16%) having urinary symptoms
      (fever, rigor, vomiting, frequency or screams during the act of urination) were
      subjected to urine culture. Data about age and sex were also collected. RESULTS:
      Frequency of urinary tract infections among children examined by urine culture
      was 36.8% (n=302), with mean age of 7.6 years. 272 (90.1%) of them were females,
      and 30 (9.9%) were males. More than half 154 (51%) of infected patients were less
      than three years old. The isolated bacteria was Escherichia coli 201 (66.3%)
      followed by Staphylococcus suprofyticus 45 (14.9%), Proteus spp 15 (4.9%),
      Klebsiella 12 (3.9%) then Enterococcus spp 12 (3.9%). Sensitivity of E. coli to
      Nalidexic acid was 70%, to Amoxicillin/Clavulanic acid was 29.9%, to Co
      trimoxasole was 16.4%, and to Nitrofurantoin was 15.9%. CONCLUSION: The majority
      of the infected patients were females and the highest frequency of the disease
      was in the first three years of age. The most common isolated microorganism was
      E. coli followed by Staphylococcus suprofyticus, Proteus spp, then Enterococcus
      spp. The highly active antibiotic for most organisms isolated was Nalidexic acid,
      then amoxicillin/clavulanic acid. Nalidexic acid can be used as a first line
      empiric treatment and/or prophylaxis of UTI in children.

PMID- 16092644
TI  - Psychiatric morbidity among Afghan refugees in Peshawar, Pakistan.
AB  - BACKGROUND: A review of the literature shows that refugees in different parts of
      the world have high rates of psychological and emotional problems. However,
      psychiatric morbidity among Afghan refugees in Pakistan has been poorly studied.
      Most of the studies of psychiatric disorders come from western countries.
      However, these studies may not be representative of the Afghan refugees in
      Pakistan. This study was carried out to measure psychiatric morbidity among a
      group of Afghan refugees attending a psychiatric clinic in Peshawar, Pakistan.
      METHODS: This is a cross sectional study, to measure prevalence of psychiatric
      morbidity among the residents of Afghan refugee camps in Peshawar, Pakistan, who
      attended a psychiatric clinic between November 2003 and February 2004. Data were
      collected using Mini International neuropsychiatry Interview Schedule (MINI), and
      a form specifically developed for the study. RESULTS: Nearly 80% of our patients
      had a diagnosis of Post Traumatic Stress Disorder. Nearly half (47.9%) reported
      family history of mental illness, while almost a quarter (23.3%) had a physical
      disability or long term illness. Only 13.7% (106) had contacted health services
      prior to seeking help for their psychiatric illness. CONCLUSIONS: A high number
      of patients presenting with PTSD is not an unusual finding when one considers the
      traumatic experiences faced by the general population of Afghanistan. Only a
      small number of the patients had been in contact with the health services prior
      to their contact with the psychiatric service. This study highlights the
      importance of health education among Afghan refugees and to establish the mental
      health services for them.

PMID- 16092645
TI  - A study of reasons of non-compliance to psychiatric treatment.
AB  - BACKGROUND: This study was carried out with an objective to find out the
      frequency of different reasons of non-compliance to treatment in a sample of out
      door psychiatric patients. METHODS: This study was conducted at Psychiatry
      department, Pakistan Institute of Medical Sciences, Islamabad, from Aug. 2001 to
      Jan. 2002. Data from a non-probability sample of two hundred follow up patients
      with a definite psychiatric illness was collected. A questionnaire designed for
      this purpose was administered by a consultant psychiatrist to the patients. The
      data was categorized into different causes of discontinuation of treatment
      accordingly. RESULTS: The commonest reasons for non-compliance were unawareness
      of the benefits of treatment (43%), nonaffordability of drugs (33.5%), physical
      side effects (28.5%), no awareness given by the doctor (03%) and unfriendly
      attitude of doctors (02%). The commonest illnesses leading to non-compliance were
      major depressive disorder (31.5%), schizophrenia (19.5%) and bipolar affective
      disorder (19%). CONCLUSION: Non-compliance is quite common in Pakistan like any
      other society. Medical practitioners need to be aware of it and address this
      problem because compliance is directly related to the prognosis of the illness.
      It is recommended that all efforts should be exerted to improve the compliance of
      psychiatric patients by eliminating the factors leading to non-compliance.

PMID- 16092646
TI  - An index of depression in patients with chronic nonspecific musculoskeletal pain.
AB  - BACKGROUND: The present study was undertaken to derive an index of depression in
      patients with chronic non-specific musculoskeletal pain and to determine
      correlation between these two parameters. METHOD: The study was carried out at
      the Shaikh Zayed Hospital Lahore from November 2001 to May 2002 and included 36
      patients with pain for at least 4-24 weeks duration; an equal number of healthy
      people acted as controls. Depression was assessed among subjects by administering
      the General Health Questionnaire (GHQ) to patients and controls and obtaining
      their GHQ scores. Pain assessment was performed in patients by scoring the total
      number of pain sites on digital palpation to provide a Total Pain Score (TPS).
      RESULTS: Patients differed significantly from controls in their GHQ scores
      (patients 20.47 +/- 7.19, controls 3.11 +/- 1.89 respectively, p<0.001). The GHQ
      score and the TPS score correlated significantly in patients (r=0.517, p=0.001).
      CONCLUSIONS: Patients with chronic non-specific musculoskeletal pain suffer from
      significant levels of depression, in direct correlation to their pain.

PMID- 16092647
TI  - Comparison of percutaneous pinning with casting in supracondylar humeral
      fractures in children.
AB  - BACKGROUND: In Children Supracondylar fracture of humerus is one of the most
      common fractures in first decade of life. There are various treatment modalities
      for this fracture i.e. Close reduction and casting, open reduction and internal
      fixation, skeletal traction and Percutaneous Pinning. This study was conducted to
      know the outcome of Percutaneous Pinning in the management of displaced
      supracondylar humeral fracture in children and to compare the results with close
      reduction and castings and published literature. METHODS: This descriptive study
      was conducted in Orthopaedic department of Ayub Teaching Hospital Abbottabad and
      Lady Reading Hospital, Peshawar from January 2002 till December 2003 on 40
      children. Patients included were of either gender with age range from 3 to 12
      years with displaced supracondylar fracture presenting within 72 hours of injury.
      Two treatment modalities were studied for comparison. Cross k-wires fixation
      through each humeral condyle was done after closed reduction of fracture under
      image intensifier in general anesthesia. Casting/Backslab was applied after
      reduction of fracture without image intensifier under anesthesia or analgesia.
      Out come measures were according to Flynn criteria that are functional and
      cosmetic factor which is based on loss of elbow motion and carrying angle in
      degrees respectively. RESULTS: Cross percutaneous pinning gave excellent results
      in 13 (65%), good outcome in 4 (20%) and poor outcome in 3 (15%) patients. While
      patients treated with close reduction and casting showed excellent results in 4
      patients (20%), good in 8 patients (40%), fair in 2 patients (10%) and poor in 6
      patients (30%). CONCLUSION: Closed reduction and cross percutaneous pinning for
      displaced supracondylar humerus fractures in children is safe, cost and time
      effective method and gives stable fixation with excellent outcome as compared to
      close reduction and casting.

PMID- 16092648
TI  - A comparison between presenatation time and delay in surgery in simple and
      advanced appendicitis.
AB  - BACKGROUND: Acute appendicitis is the most common cause of acute abdomen. Serial
      examinations and investigations increase diagnostic accuracy. But this causes
      delay, which may result in gangrene and perforation. Our aim is to determine the
      affect of delay by the patient as well as by the physician on the stage of the
      disease as determined intraoperatively and to determine the percentage of
      negative appendectomies. METHODS: 102 consecutive patients presenting to the Mayo
      Hospital emergency, undergoing appendectomy between February and April, 2002
      comprise the study group. Data was tabulated and analyzed. The delay by the
      patient in presenting to emergency was called the "patient's delay" and the in
      hospital delay before the actual operation called the "physician's delay" were
      calculated. The appendicitis was divided into two groups i.e. "simple
      appendicitis" which included acutely inflamed appendices and grossly mildly or
      non inflamed but histopathologically inflamed appendicitis and "advanced
      appendicitis" which included gangrenous and perforated cases. RESULTS: The
      percentage of negative appendectomy in our center was 5.9%. Patients' delay
      averaged 2.59 days and 2.43 days in simple and advanced appendicitis. A prolonged
      average delay period of 6.12 day was seen in misdiagnosed cases. The mean delay
      was not significantly different. 86.3% of the patients were operated within 12
      hours of presentation. The mean physician's delay was 9.24 hours. It was
      significantly shorter for advanced appendicitis as compared to simple
      appendicitis. CONCLUSIONS: Patient's delay was not associated with advanced
      appendicitis. It is recognizable clinically and gets operated two hours earlier
      on average. There is a significant lag period of observation leading to a
      physician delay in simple appendicitis, contributing possibly to, increased
      morbidity. However there is an increased need to use ultrasonography and CT in
      the emergency setting to diagnose appendicitis in case of doubt.

PMID- 16092649
TI  - Evaluation of emergency revascularisation in vascular trauma.
AB  - BACKGROUND: Vascular trauma is a common life threatening injury leading to
      serious consequences if not timely and efficiently managed. We evaluated early
      surgical interventions aimed at revascularization and thus salvaging limb/organ
      in life threatening vascular injuries. Aims of our study were to evaluate the
      outcome of available diagnostic modalities, earliest possible surgical
      intervention and rate of related complications with particular reference to our
      existing situation. METHODS: Emergency diagnostic workup based mainly on clinical
      evaluations and required laboratory and imaging parameters leading to
      revascularisation was performed in 48 patients in Combined Military Hospital
      (CMH) Muzaffarabad and Islamic Medical College Hospitals between June 1997 and
      December 2001. Data was collected on pre-designed computerized proforma's which
      were completed by the treating surgeon and data was entered and analyzed
      accordingly. RESULTS: Out of the total 48 patients who sustained major vascular
      injuries during this period, 14 (29.2%) were having injury to upper limb vessels,
      26 (54.2%) patients had injury to the lower limb vessels, 6 (12.5%) patients
      reported with injury to abdominal vessels. One (2%) patient had injury to common
      carotid artery, while an other patient to thoracic aorta respectively (2%).
      Penetrating trauma caused 38 (79%) and blunt trauma caused 10 (21%) major
      vascular injuries. Out of 48 patients, 41 (85.4%) patients were successful
      managed by vascular reconstruction without any residual disability. CONCLUSION:
      Speedy diagnostic work up and early revascularization yields favourable outcome
      in vast majority of patients requiring vascular repair. Selections of surgical
      technique including use of autologous vein graft or artificial vascular graft can
      save many limbs. In order to achieve good results the time lapse between injury
      and revascularisation should be less than 6 hours.

PMID- 16092650
TI  - Outcome of plating, bone grafting and shortening of non-union humeral diaphyseal
      fracture.
AB  - BACKGROUND: Humeral diaphyseal fracture usually heals with closed methods but
      when non union develops then it needs surgical intervention in the form of
      plating and bone grafting, intramedulary nailing (open or closed simple or
      interlocking nails) and external fixators (circular or one plane fixator). In our
      unit we treated non union humeral diaphyseal fracture with plating and bone
      grafting and shortening of fracture ends up to 4 to 5 cm when needed. METHODS:
      This study was conducted at Orthopaedic Department of Ayub Teaching Hospital
      Abbottabad from January 2002 till December 2003. We included 15 cases with
      atrophic non-union in 9 (60%) and hypertrophic non-union in 6 (40%) patients. All
      atrophic non-union were treated with plating, bone shortening by transverse
      osteotomy and bone grafting, while hypertrophic non-union were treated with
      decortications of non-union ends and fixation with compression plates, with bone
      grafting in old age. Follow up measures were based on clinical (range of joints
      motion) and radiological (healing) findings. Follow up was done for up to 6
      months. RESULTS: Out of 15 patients the age range was 20-80 years, 12 (80%) were
      male and 03 (20%) female. Right humerus involved in 5 (33.33%) while left humerus
      in 10 (66.66%) patients. In 9 (60%) patients with atrophic non union bone
      shortening by transverse cut osteotomy was done while in remaining patients with
      hypertrophic non-union plating was done in 2 (13.33%) cases and plating with bone
      grafting in 4 (26.66%) patients. Union was achieved in all patients after 16 to
      20 weeks of surgery. In one patient (6.66%) of 75 years age with hypertrophic non
      union implant was loosened after 03 months of surgery. At that time healing
      (Union) was evident on X-rays and humeral brace was applied for further 03
      months. Two patients (13.33%) got neuropraxia of radial nerve which resolved with
      in 3 months time. 02 patients (13.33%) developed shoulder stiffness which
      resolved after exercise. CONCLUSION: In Non Union of Humerus shortening by
      transverse osteotomy & rigid fixation with plates give excellent results in
      selected cases.

PMID- 16092651
TI  - A two years audit of complications of hysterectomy at Ayub Teaching Hospital
      Abbottabad.
AB  - BACKGROUND: Hysterectomy is one of the most common major surgical procedures
      performed in Gynaecology. Our objective was to determine the operative and
      postoperative complications of this procedure with an aim to improve management
      at our unit. METHODS: This study was conducted in the Department of Gynaecology,
      Ayub Teaching Hospital, Abbottabad form January 2002 to December 2003.
      Indications, complications and mortality associated with hysterectomy were
      assessed. RESULTS: Total number of hysterectomies performed in two years at our
      unit was 316. Major Indications for hysterectomies were dysfunctional uterine
      bleeding (38%) and fibroid uterus, (27%) followed by prolapse (22%).
      Complications developed in 14% out of these. The frequency of complications was
      related with indication for hysterectomy, age, parity and history of associated
      serious illness. It was found that frequency of complications in fibroid uterus
      was higher (1.2%) than that for Dysfunctional uterine bleeding (DUB) (1.0%).
      There was no operative death, while 5 (1.5%) patients died within 2 weeks of
      surgery. CONCLUSION: We have a fairly high frequency of morbidity and mortality
      associated with hysterectomy. In order to reduce these proper selection, pre
      operative preparation and less invasive alternative treatment for the commonest
      indications of hysterectomy (that is fibroids and DUB) for example various
      methods of endometrial ablation or resections can be employed.

PMID- 16092652
TI  - Presentation of polycystic ovary syndrome and its management with clomiphene
      alone and in combination with metformin.
AB  - BACKGROUND: This study was carried out to determine the pattern of presentation
      of Polycystic ovary syndrome (PCOS) in patients presenting at our unit and to
      compare effects of clomiphene alone and in combination with metformin in
      management of PCOS. METHODS: This study was conducted from Jan 2001-2003 at
      Military Hospital, Rawalpindi. All patients presenting with infertility were
      evaluated with a view to select 100 patients of PCOS with the help of history of
      oligomenorrhoea, hirsuitism and acne. Diagnosis was confirmed by ultrasonography
      and hormone analysis (LH, FSH, prolactin, testosterone along with LH:FSH>2). The
      100 selected patients were divided into two equal groups. One was given combined
      clomiphene citrate (CC) and metformin for ovulation induction and the other CC
      alone. These patients were followed for six cycles for ovulation and conception.
      Follicle tracking on ultrasonography and day-21 serum progesterone level were
      used to detect ovulation while conception was confirmed by urine pregnancy test,
      serum B-HCG level and ultrasonography for gestational sac. RESULTS: Hirsuitism
      and oligomenorrhoea were the two most common clinical features of PCOS. In the
      first group 34 patients (68%) ovulated as compared with 18 (36%) in the second
      group. In the first group 18 out of 34 women (52.9%) conceived as compared with
      only 8 out of 18 (44%) in the second group. The difference was significant at
      >0.05 when ovulatory and pregnancy responses were compared among two groups. All
      patients tolerated metformin well and no teratogenic effects were observed in
      patients who conceived after treatment with metformin. CONCLUSION: A combination
      of metformin and clomiphene citrate significantly increases the ovulation and
      conception rates in these patients.

PMID- 16092653
TI  - Screening of pregnant women for gestational diabetes mellitus.
AB  - BACKGROUND: Gestational diabetes mellitus is associated with significant fetal
      and neonatal morbidity and mortality. It is a definitive risk factor for the
      future development of type-II diabetes mellitus in the mother. Our objective was
      to evaluate the effectiveness of screening by 50 gm oral glucose challenge test
      to detect the gestational diabetes mellitus and impaired glucose tolerance in
      pregnant women. METHODS: This study was conducted in the Department of
      Gynaecology at Lady Reading Hospital, Peshawar. A total of 1000 women were
      screened in antenatal clinic by giving them 50 gm oral glucose solution and
      estimation of plasma glucose level 1 hour after glucose intake. Those with plasma
      glucose in excess of 130 mg/dl (cut off value for screen positive) were subjected
      to 3 hours oral glucose tolerance test to confirm the diagnosis of gestational
      diabetes mellitus. RESULT: Out of 1000 cases tested, 43 were found to have
      Gestational Diabetes Mellitus and 17 cases had impaired glucose tolerance. The
      mean age of the patients ranged between 21 and 42 years. Most of the positive
      patients carried medical and obstetric historic risk factors for diabetes
      mellitus like obesity, advanced age and parity and bad obstetric history. They
      also had associated complications of gestational diabetes mellitus like pre
      eclampsia and polyhydramnios in current pregnancy. Also more than 80% of the
      patients had family history of risk factors like diabetics mellitus, obesity,
      hypertension etc. CONCLUSIONS: 50 gm Oral Glucose Challenge Test can be used in
      pregnant ladies from 24 weeks onward to detect the common disorders of
      Gestational Diabetes Mellitus and Impaired Glucose Tolerance.

PMID- 16092654
TI  - Presentation and management outcome of eclampsia at Ayub Teaching Hospital,
      Abbottabad.
AB  - BACKGROUND: This study was carried out evaluate to epidemiology, clinical
      presentation and prognostics aspects of patients presenting with eclampsia.
      METHODS: This study was carried out at Gynae "C" unit of Ayub Teaching Hospital
      Abbottabad from 1st July 2003 to 31st October 2004. All patients presenting with
      eclampsia to the labor ward were included in the study. The diagnosis was based
      on history and confirmed on clinical findings of hypertension, oedema,
      proteinuria superimposed with fits. Patients with history of fits during
      pregnancy, labor and peurperium other than eclampsia were excluded from study.
      History physical findings and base line investigation were recorded on a
      proforma. RESULTS: A total of 2100 admissions were made in the labor ward during
      this period and out of them 68 cases (3.23%) were of eclampsia. Out of them 28
      were primigravidae, 14 multigravidae and 26 grandmultigravidae. The seasonal
      frequency of cases was 29.41% in winters, 42.64% in autumn, 19.11% in summers and
      8.82% in spring. Out of these 11.76% cases were complicated with retroplacental
      haemorrage and the same number with aspiration pneumonia, while Cerebrovascular
      Accident (2.94%) Acute tubular necrosis (2.94%) and Disseminated intravascular
      clotting (4.4%) were also seen. Among the new borns prematurity was found to be
      the major cause of perinatal mortality. CONCLUSION: Eclampsia is a dreadful
      complication of Pre Eclamptic Toxemia of pregnancy associated with high perinatal
      and maternal mortality. A qualitative and quantitative improvement in prenatal
      consultation should make it possible to reduce incidence of eclampsia measuring
      arterial blood pressure daily during antenatal period and for at least 14-days
      postpartum appears to be necessary for diagnosis and treatment for all cases of
      hypertension.

PMID- 16092655
TI  - Glycemic control, hypertension and chronic complications in type 2 diabetic
      subjects attending a tertiary care centre.
AB  - BACKGROUND: This study was carried out to assess the association of glycemic
      control and hypertension with chronic complications in type 2 diabetic subjects
      attending a tertiary care centre in Karachi, Pakistan. METHODS: This was a cross
      sectional analytical study. First visit of type 2 diabetic subjects to the
      outpatient department of Baqai Institute of Diabetology and Endocrinology, from
      September 1996 to December 2001, were analyzed for this study. Sociodemographic
      attributes and clinical profiles were obtained from the computerized records of
      these patients retrospectively. Odds ratio with 95% confidence interval were
      reported for independent variables associated with outcome variables. RESULTS:
      Records of 2199 subjects (48.5% males, 51.5% females) were analyzed. Mean age of
      the male and female subjects was 52.2 and 50.6 years respectively.
      Hypertriglyceridemia [OR: 1.74; 95% CI (1.18-2.57)] and diabetic foot ulcers [OR:
      2.32; 95% CI (1.14-4.01)] were significantly associated with poor glycemic
      control according to HbA1c. Whereas hypertriglyceridemia [OR: 2.39; 95% CI (1.42
      4.03)] and hypertension [OR: 1.65; 95% CI (1.13-2.41)] were significantly
      associated with poor glycemic control according to FPG. Obesity [OR: 1.44; 95% CI
      (1.18-1.75)], Retinopathy [OR: 1.95; 95% CI (1.49-2.53)], nephropathy [OR: 1.99;
      95% CI (1.45-2.75)], neuropathy [OR:1.40; 95% CI (1.15-1.71)] and presence of
      coronary arterial disease [OR: 1.33; 95% CI (1.02-1.72)] were found to be
      significantly associated with systolic blood pressure. Obesity [OR:2.07; 95% CI
      (1.69-2.54)], hyperglycemia [OR: 1.40; 95% CI (1.04-1.90)] and nephropathy [OR:
      1.92; 95% CI (1.39-2.64)] had significant association with high diastolic blood
      pressure. CONCLUSION: In conclusion this study shows the association of chronic
      complications with glycemic control and hypertension amongst type 2 diabetics in
      Karachi. This information needs to be verified by multicentred large scale
      studies in order to be helpful in planning healthcare and treatment strategies.

PMID- 16092656
TI  - Comparison of effects of extract of Myristica fragrans and verapamil on the
      volume and acidity of carbachol induced gastric secretion in fasting rabbits.
AB  - BACKGROUND: Peptic ulcer is mostly produced due to the over production of gastric
      acid. This study was undertaken to find out the effects of extract from Myristica
      fragrans which contains documented natural Calcium channel blocker and Verapamil
      on volume and acidity of Carbacol induced gastric section. Their effects were
      also compared to find out any difference in their efficacy. METHODS: Thirty
      rabbits of local breed, weighing 1-1.5 kg were used. The animals were kept on
      fasting for 48 hours, after which the pylorus of each animal was ligated.
      Verapamil 10 mg/kg, Myristica fragrans 500 mg/kg and Carbachol 600 microg/kg body
      weight were administered intraperitoneally. RESULTS: It was found that extract
      from Myristica fragrans reduced the volume, free and total acidity of gastric
      secretion, which were statistically highly significant when compared with
      Carbachol (P<0.001). Verapamil had also the same effects. When the difference of
      mean for verapamil was compared with that of extract, all these differences were
      found statistically non significant indicating that extract has similar effect as
      that of Verapamil on all parameters included in study. CONCLUSION: The effect of
      Myristica fragrans is similar to Verapamil and therefore it can be used
      effectively in the treatment of peptic ulcer and all other conditions that
      require calcium channel blockers for the treatment of these disorders.

PMID- 16092657
TI  - Effect of Nigella sativa (kalonji) on serum cholesterol of albino rats.
AB  - BACKGROUND: The increased level of LDL-c in the serum has a high risk and the
      increased serum HDL-c level has a low risk for the development of
      atherosclerosis. The effect of Nigella sativa on levels of cholesterol fractions
      were determined in this study on rats. METHODS: 24 albino rats of 08 weeks age
      having equal number of males and females were kept at optimum atmospheric
      condition. The blood samples were taken at the start and different control and
      experimental diets were given for 20 weeks. The experimental diets were added
      with Nigella sativa as 30 mg/kg body weight. The blood samples were taken at the
      end of study. The blood samples drawn at the start and end of the study were
      estimated for serum cholesterol. The results of control and experimental groups
      were compared. RESULTS: Total serum cholesterol in the control group showed
      increase from 8.3+/-3.30 to 13.96+/-9.3 at 20 weeks. The serum HDL cholesterol
      showed increase from 44.4+/-6.12 to 80.45+/-5.95 level at 20 weeks. The serum LDL
      cholesterol showed increase from 8.3+/-3.30 to 13.96+/-9.3 at 20 weeks. The total
      serum cholesterol in experimental group was increased from 76.9+/-6.5 to 117.5+/
      6.65 at 20 weeks. The serum HDL cholesterol levels was increased from 41.7+/-4.9
      to 83.42+/-5.92 at 20 weeks as compared with control group. The LDL cholesterol
      levels were decreased from 12.7+/-6.9 to 8.5+/-7.8 at 20 weeks. CONCLUSION: This
      study shows significant decrease in serum low density lipoprotein cholesterol
      level, and increase in serum high density lipoprotein cholesterol levels.

PMID- 16092658
TI  - An audit of serological tests carried out at clinical laboratory of Ayub Teaching
      Hospital, Abbottabad.
AB  - BACKGROUND: Clinical audit is an important tool for reviewing and improving the
      quality of service in clinical laboratories. Here we present an audit of total
      serology test requests and the frequency of positive tests out of these in a
      calendar year. METHODS: This is an audit of serology tests carried out at
      Microbiology section of Clinical Laboratory of Ayub Teaching Hospital,
      Abbottabad. We counted all the serology test requests for the year 2004. These
      tests requests were grouped month wise. The frequency of positive tests out of
      the total test requests were calculated. The tests included Widal, Toxoplasma,
      Brucella, Anti DNA, Anti Nuclear factor (ANF), Rheumatoid Arthritis Factor (RAF),
      HIV, HBsAg, HCV, Intra Chromatographic Technique for tuberculosis (ICT-TB),
      Purified Protein Derivative (PPD), Venereal Disease Research Laboratory (VDRL)
      test, Anti-Streptolysin-O-test (ASOT) and pregnancy test. RESULTS AND
      CONCLUSIONS: This audit gives a clear idea of trends of test requests in our
      hospital. It reflects accuracy of clinicians' judgment in some tests and failure
      in others, prevalence of different diseases, seasonal variation in number of test
      requests for some tests and impact of awareness campaigns on attitude of
      clinicians towards certain diseases. This will help us in planning our laboratory
      requirements to improve quality.

PMID- 16092659
TI  - Clinical presentation of urinary tract infection among children at Ayub Teaching
      Hospital, Abbottabad.
AB  - BACKGROUND: Urinary tract infection (UTI) is still common among children all over
      the world and a cause for significant number of out patient visits. Keeping in
      view the high incidence of UTI in children with associated morbidity and
      mortality, it is imperative to diagnose the urinary tract infection early and to
      treat the infection. We carried out this study to look into the clinical profile
      of UTI in children presenting at Ayub Teaching Hospital. METHODS: One hundred
      patients of diagnosed UTI, from 0 to 15 years of age admitted in the Pediatric
      units of Ayub Teaching Hospital Abbottabad were included in the study. A proforma
      was used to record the clinical and laboratory presentation of these patients.
      RESULTS: Fever was the commonest clinical presentation (92%) followed by dysuria
      (68%) and failure to thrive (31%). CONCLUSION: Clinical profile of urinary tract
      infection in children in this study was not significantly different from that of
      other developing and developed countries, however it will help us a lot in speedy
      diagnosis of our Paediatrics patients.

PMID- 16092660
TI  - Diagnostic and therapeutic implications of ST-segment elevation in lead aVR of 12
      lead ECG during chest pain.
AB  - 'aVR' is usually not the preferred lead to diagnose myocardial infarction in
      clinical settings, it is rather a neglected lead in this context. We describe the
      case of a 44 year old male who presented with short duration chest pain and ST
      segment elevation in lead 'aVR'. His left heart catheterization showed left main
      stem equivalent disease and totally occluded right coronary artery. Patient
      underwent emergency coronary artery bypass-grafting with favorable outcome. This
      case highlights the significance of ST segment elevation in lead aVR during chest
      pain both in diagnosis and management of patients with acute coronary syndrome.

PMID- 16092661
TI  - Papillon-Lefevre syndrome.
AB  - A 9 year old male presented with keratotic plaques over the skin of his palms and
      soles extending onto the dorsal surface and swollen gums since the age of 4 with
      subsequent loss of most of his permanent dentition. These findings are consistent
      with Papillon-Lefevre syndrome.

PMID- 16092662
TI  - Isolated appendicular tuberculosis.
AB  - Tuberculosis is still very common in developing and under developed countries.
      Each year, 3 million people die of this disease world wide. Tuberculosis can
      affect almost any part of body. The commonest presentation of abdominal
      tuberculosis is ileo-caecal disease, but isolated appendicular involvement is
      also rarely seen. Although many cases have been reported from neighbouring
      countries, a search on national literature has shown no such report from
      Pakistan. We report a case of appendicular tuberculosis that presented in
      Accident and Emergency Department of Pakistan Institute of Medical Sciences,
      Islamabad.

PMID- 16092663
TI  - Is the high frequency of diabetes type 2 in chronic hepatitis C virus infection
      due to strong family history?

PMID- 16092665
TI  - Cervical carcinoma: conventional screening methods efficient enough?
AB  - Organized screening for cervical carcinoma has already demonstrated its
      efficiency in industrial countries but it still has to be better organized,
      particularly in developing countries. In the European Union, results may be
      improved thanks to more cooperation with Health authorities, enabling the
      pathologists to focus the risk evaluation and to broadcast recommendations about
      prevention on a population level.

PMID- 16092664
TI  - Correlates of consulting health professionals for mental health in Canada and
      United States.

PMID- 16092666
TI  - Gastrointestinal stromal tumors. A multicenter experience.
AB  - The report presents 200 cases of gastrointestinal stromal tumors (GIST). The
      material originated from six diagnostic centers in Poland and was reclassified
      according to the current criteria. Among lesions other than GISTs, 14 were
      identified as smooth muscle tumors and seven as neural tumors. GISTs were located
      in the stomach (51-63.3% of the investigated series), small intestine (27.4
      33.8%), colon (approximately 4.5%), abdominal cavity, i.e. in the peritoneum and
      omentum (6%), and in the retroperitoneal space (2.5%). A slight predominance of
      women was noted (53-56%). The age of the patients ranged between 14 and 93 years
      of life, with the mean age of 62.4 years. Individuals younger than 45 years of
      age accounted for 10% of the group. In ten patients (five of them less than 45
      years of life), multiple tumors were detected, their number ranging from two to
      less than 20; these individuals constituted 5% of the entire series. Moderately
      and highly aggressive tumors predominated. In the series, when multiple tumors
      were excluded, a total of 24 epithelioid GISTs (12%) were observed; of this
      number, 13 were situated in the stomach, six--in the small intestine, two--in the
      abdominal cavity and another two in the retroperitoneal space. Synchronic tumors
      observed in patients with GISTs were seen in seven patients, including an
      adenocarcinoma of the colon, two adenocarcinomas of the stomach, a carcinoid
      tumor of the small intestine, a pheochromocytoma of the retroperitoneal space, an
      anaplastic lymphoma and a disseminated squamous cell carcinoma. In
      immunohistochemical reactions (CD117, CD34, SMA, S-100, DES), attention was
      focused on the immunoreactivity of small GISTs, below 2 cm in size, and of
      multiple tumors. Immunohistochemical reactions were equally differentiated as to
      their presence and intensity in small tumors and in highly aggressive lesions
      above 5-10 cm in size. In multiple GISTs, immunohistochemical tests strongly
      indicated the heterogeneity of neoplastic cells, which, nevertheless, showed no
      consistent association with the location of the tumor, its aggressiveness,
      cellular structure or a tendency to form multiple foci.

PMID- 16092667
TI  - Immunohistochemical analysis of the interstitial mast cells in rebiopsied
      patients with idiopathic mesangial proliferative glomerulonephritis.
AB  - Recent evidence suggests a role for mast cells in the pathogenesis of renal
      scarring in various glomerulopathies, therefore the present study was undertaken
      to evaluate whether mast cells have a role in tubulointerstitial fibrosis in
      rebiopsied patients with idiopathic mesangial proliferative glomerulonephritis
      (MPG) and to examine a possible relationship between mast cells and interstitial
      alpha-smooth muscle actin (alpha-SMA) expression as well as interstitial
      infiltrates. Seventeen patients with idiopathic mesangial proliferative
      glomerulonephritis, in whom renal biopsies were repeated and for whom light and
      electron microscopy as well as immunofluorescence microscopy and full clinical
      data were available were examined quantitatively. Morphometric investigations
      were performed by means of a computer image analysis system. The study revealed
      that at the rebiopsy proteinuria was significantly lower as compared with the
      first biopsy. On the other hand, the mean values of the interstitial tryptase
      positive cells, expression of alpha-SMA, interstitial volume and CD68+ cells were
      at rebiopsy significantly increased. The mean values of CD45RB+, CD43+ and CD20+
      cells did not differ significantly in these groups. In both initial biopsy and
      rebiopsy groups there were significant positive correlations between interstitial
      tryptase positive cells and interstitial expression of alpha-SMA, interstitial
      volume, and CD68+ cells. The present quantitative study may suggest that despite
      of the clinical improvement at rebiopsy, MPG is a progressive glomerular disease,
      and point to a role of mast cells in this process.

PMID- 16092668
TI  - Prognostic value of immunohistochemical estimation of CD24 and Ki67 expression in
      cisplatin and paclitaxel treated ovarian carcinoma patients.
AB  - CD24 is a small membranous protein which may participate in invasion of tumor
      cells. Present study aimed at evaluation of prognostic significance linked to
      immunohistochemical demonstration of CD24 expression and the proliferation index,
      Ki67 expression in ovarian cancers. The immunohistochemical reactions with
      monoclonal CD24- and Ki67-specific antibodies were performed in paraffin sections
      originating from 30 patients with ovarian cancer treated using cisplatin and
      paclitaxel. Results of the reactions and analysis of the clinical course of the
      patients were subjected to statistical analysis. Cases with cytoplasmic
      membranous expression of CD24 (CD24c-m) were found to exhibit significantly
      shorter overall survival time (P = 0.0002) and progression-free period (P =
      0.0005). Cases with membranous expression of CD24 (CD24m) manifested a longer
      overall survival time (P = 0.022). No relationship was disclosed between
      expression of Ki67 on the one hand and survival time and CD24 expression on the
      other. As documented using chi square test, expression of CD24c-m predisposed to
      relapses (P = 0.012), progression (P = 0.0362) and to death (P = 0.0034). Deaths
      were encountered significantly less frequently in cases with CD24m expression (P
      = 0.0465). The studies demonstrated that CD24c-m represented a strongly
      unfavorable prognostic indicator. The antigen represents an interesting target in
      the search for novel therapeutic methods. The more aggressive course of cases
      with CD24c-m expression was not linked to more intense proliferation of the tumor
      cells.

PMID- 16092669
TI  - Medianecrosis of the aorta (MNA)--Gsell-Erdheim syndrome: main histopathological
      features.
AB  - Twenty four cases of Gsell-Erdheim syndrome observed in 1999-2001 have been
      examined. There were 20 men (83.4%) and 4 women (16.6%). The age ranged from 22
      to 69 years but 6 men (25%) died at age under 50. The following variants of
      aortic lesions were revealed in autopsy material: intimal tear with the following
      dissection which extends along the aorta to variable distances--in most cases
      into iliac arteries. The morphologic changes, associated with were: anuclear
      zones, elastolysis, thinning, dyschromia and fragmentation of elastic fibers,
      focal hyperelastosis. Such changes were revealed in all parts of the aortic wall,
      independently of the site of rupture.

PMID- 16092670
TI  - Mesothelial inclusion cysts (so-called benign cystic mesothelioma)--a
      clinicopathological analysis of six cases.
AB  - The report presents six cases of mesothelial inclusion cysts (MIC), detected in
      five females (22-53 years of age) and one male (47 years old). The lesions were
      unifocal (four cases) and multifocal (two cases), and were located on the surface
      of the peritoneum in the cul de sac, on the intestines, urinary bladder, uterine
      adnexa, also involved round ligament within the pelvis and in the inguinal canal
      (one patient). Additionally, in one female, small cysts, free-floating in the
      peritoneal cavity were present. In three patients, clinical signs resulted
      directly from the presence of MIC. One female had been 7 years previously
      operated on due to endometrioid ovarian cysts. Apart from MIC, three patients
      presented with concomitant diseases: appendicitis (two cases), peritoneal
      pseudomyxoma or primary ovarian carcinoma. Gross appearance: the lesions were
      polycystic, the surgical materials ranging from three fragments measuring 0.5 cm
      each to seven fragments, with the maximum size of 14x6 cm. The cysts were from
      microscopic size to 2 cm in diameter, the majority were thin-walled,
      semitranslucent, filled with clear or yellowish fluid or gelatinous contents. In
      one case, the cyst walls were thicker and showed intense inflammatory lesions and
      fibrinous exudate. Microscopically, the majority of cysts were lined with a
      single layer of flattened or cuboid mesothelial cells (CK+, calretinin+). In two
      patients, the mesothelium demonstrated diffuse squamous cell metaplasia; in one
      individual, the cells focally formed small papillae and were vacuolated. No mucus
      was observed either in the cytoplasm or outside the cells. Immunohistochemical
      reactions to CEA, ER, PR and MIB-1 were negative. Intramural proliferations and
      intracystic detached clumps of cells showed both mesothelial cells (without any
      mitotic activity and signs of atypia) and macrophages (CD68+). To date, the
      follow-up has been 7 years and 3 years in two individuals, and from 1 to 7 months
      in the remaining three patients--all of them are free from recurrent disease. One
      female failed to report for follow-up examinations. The report also presents the
      review of literature.

PMID- 16092671
TI  - Colonic adenocarcinoma with numerous paneth and endocrine cells.
AB  - Numerous granular eosinophilic cells corresponding to Paneth cells were
      unexpectedly revealed in a moderately differentiated adenocarcinoma of the
      hepatic flexure of the colon in a 76-year-old man. These cells were clearly seen
      in routine slides and their nature was confirmed by Masson's trichrome stain, by
      immunohistochemical reaction for lysozyme, and by electron microscopy. The tumor
      contained also cells intermediate between Paneth and goblet cells (with both
      supranuclear granules and mucous globules), observed in Masson's trichrome stain
      and in electron microscope. Additionally, immunohistochemical reaction for
      chromogranin A was performed and irregularly scattered neoplastic endocrine cells
      were visualized in the tumor. The light microscopic and ultrastructural features
      of this rare neoplasm are described together with detailed clinical data. The
      incidence and significance of the Paneth cell and endocrine differentiation in
      colorectal carcinomas are discussed with the review of the literature.

PMID- 16092672
TI  - Cystic nephroma in adults. A report of two cases and review of the literature.
AB  - We present two cases of cystic nephroma in a 55-year old and a 61-year old women.
      In both patients the results of ultrasound and clinical examinations were not
      characteristic enough to establish the precise preoperative diagnosis. Due to the
      age of the patients and the location of the lesions, possibility of clear cell
      carcinoma with cystic changes was considered. However, microscopic examination of
      postoperative specimens revealed benign nature of the tumors.

PMID- 16092673
TI  - Rare pancreatic tumour in a 16-year-old girl: a case report.
AB  - A 16-year-old girl was admitted to a hospital after having noticed clearly
      palpable abdominal mass, without accompanying symptoms. At surgery a tumour
      superficially attached to the pancreatic tail, well-encapsulated, measuring
      approx. 8x5x3 cm, had been found and resected. Histological examination using
      routine hematoxylin and eosin staining, additional histochemical and
      immunohistochemical techniques revealed low-grade tumour with mixed appearances
      of PSEN and pancreatoblastoma; both of these tumours originate from pancreatic
      primordia.

PMID- 16092674
TI  - International Meetings of Veterinary Pathologists in Olsztyn.

PMID- 16092675
TI  - [Clinical usefulness of the ImmunoCyt urinary test in the follow-up protocol of
      patients with urothelial neoplasms].
AB  - OBJECTIVES: The overall objective of this study was to carry out a prospective
      investigation of the usefulness of the IMMUNOCYT commercial kit in the follow-up
      of patients treated for bladder cancer and to evaluate its utility as a
      complement to urinary cytology and a possible tool for reducing the number of
      follow-up cystoscopies required. SUBJECTS AND METHODS: From September 2001 to
      December 2002, the ImmunoCyt test and urinary cytology were performed in urine
      simples from a total of 136 patients (115 with a history or suspicion of bladder
      cancer and 21 patients with other urological pathologies). Urine simples were
      fixed with an equal volume of 50% alcohol. Urinary cytology and the ImmunoCyt
      test were interpreted by a cytopathologist unacquainted with the result of the
      corresponding cytology and bladder biopsy report. Samples were staged and graded
      using the 1997 TNM classification of the UICC and the 1998 WHO/ISUP
      classification. Histopathological confirmation of lesions was available for 111
      patients (81.6%). RESULTS: The gender distribution was 89% men and 11% women.
      Mean age was 71.68 years (range 27 to 98 years). Overall sensitivity and
      specificity were 77.9% and 92.3% for the ImmunoCyt test and 47.9% and 100% for
      urinary cytology, respectively. The positive (PPV) and negative predictive values
      (NPV) were 96.4% and 61.7%, respectively, for the ImmunoCyt test and 100% and
      36.7% for cytology. In Ta and low-grade carcinomas, the sensitivity of the
      ImmunoCyt test was 70% (n=20) and 76.4% (n=34) respectively, whereas it was 25%
      (n=28) and 29.7% (n=37), respectively, for urinary cytology. The differences
      observed between the sensitivities of the ImmunoCyt test and cytology were
      statistically significant (X2 p<0.05) overall and for Ta and low-grade
      carcinomas. The sensitivity and specificity of the combination of both tests were
      86.8% and 96.2%, respectively. The sensitivity of the combination of both tests
      for Ta and low-grade carcinomas was 80% (n=20) and 82.3% (n=34), respectively.
      The ImmunoCyt test was diagnostic in 36.2% of tumors overall. CONCLUSIONS: In
      view of the results obtained, we decided to change our follow-up protocol to
      reduce the number of follow-up cystoscopies by 32.2% in the first 5 years of
      postoperative follow-up (in a cohort of 140 patients who undergo surgery
      annually). This benefits patients by reducing the number of urinary infections
      and iatrogenesis originated by follow-up cystoscopy. In addition, this 32.2%
      reduction in the number of cystoscopies in 5 years will yield a savings of
      approximately 35,560 EUR to the health care system in 5 years.

PMID- 16092676
TI  - [Radical prostatectomy. A review of our series between 1997-2003].
AB  - OBJECTIVE: To evaluate the complications and results of our series of 398 radical
      retropubic prostatectomies as an elective treatment for clinically localized
      prostate cancer. PATIENTS AND METHODS: Between January 1997 and June 2003, a
      total of 398 radical retropubic prostatectomies have been performed. Mean age was
      63.8 years (45.8-78.2), mean PSA at diagnosis 9.32 ng/ml (0.9-129.7). Mean
      surgical time was 141.6 minutes (70-280), and mean hospitalization was 6.75 days
      (2-37). RESULTS: Mean follow-up was 65.18 months. We report as peroperatory
      complications: rectal injury 1.8%, lymphatic leakage 0.3%, urinary fistula 5%. As
      delay complications: uretrovesical junction stenosis 6%. We observed 49.1% of
      patients with positive surgical margins. We don't report any peroperatory death.
      The overall survival rate is 98.5%, the cancer specific survival rate is 99.75%,
      and the recurrence-free survival rate is 84.97%. CONCLUSIONS: Radical retropubic
      prostatectomy is an excellent treatment form for patients with clinically
      localized prostate cancer. A strict selection of patients candidates is important
      to obtain good results.

PMID- 16092677
TI  - [Periprostatic anaesthesic infiltration for prostatic biopsy: a prospective,
      randomized, double blind and placebo-controlled study].
AB  - A prospective, randomized, double blind and placebo-controlled study to evaluate
      the effectiveness of periprostatic infiltration with lidocaine to reduce pain of
      prostatic biopsy. In a thirteen months period of time, 115 patients were
      randomized to receive 10 ml of lidocaine 1% (n=60) or saline (n=55). Evaluating
      the pain with visual analogue scale (0-10), the first group referred average pain
      of 3.83 and the second group of 6.87, being this difference clearly significant
      (p<0.005). There were not complications from anesthesic puncture. The
      periprostatic infiltration is easy to perform without complications and it is
      effective in reducing the pain of this procedure. It should be used as a routine
      procedure in prostatic biopsy.

PMID- 16092678
TI  - [Adjuvant and salvage radiotherapy after radical prostatectomy].
AB  - After radical prostatectomy is important to identify patients who have a high
      risk of microscopic residual disease without micrometastatic disease. Adjuvant
      RT, in retrospective studies, reduce the risk of recurrence and is more
      efficacious than salvage RT and can improve PSA relapse-free survival and should
      have an impact on long-term overall survival. The benefit of androgen suppression
      could be due to a synergistic interaction and may possibly eliminate occult
      systemic disease. Appropriate selection to identify subgroups of patients who may
      benefit from salvage RT, even for those patients at the highest risk; and whether
      some form of hormone ablation should accompany. To predict the biochemical
      failure and the risk of metastatic disease after salvage RT. We analyze the
      references to select an appropriate therapy. Improved outcomes will need to be
      tested in randomized trials.

PMID- 16092679
TI  - [Radiation-induced infiltrating transitional cell carcinoma].
AB  - INTRODUCTION: The increased risk of developing a transitional cell carcinoma
      (TCC) among patients irradiated for other pathologies in a known fact, but many
      times forgotten due to its low incidence. Our aim is to review the association
      between radiotherapy (RT) and muscle-infiltrating TCC among our patients.
      MATERIAL AND METHODS: Clinical survey among our muscle-infiltrating TCC data base
      since 1975. Descriptive analysis of found cases. RESULTS: We found 5 patients who
      developed muscle-infiltrating TCC with a mean time of 19.2 years since
      radiotherapy (three of them more than 20 years and the other two less than 10
      years). Three patients also developed other tumours or pathologies related to
      radiotherapy. Two of them had an upper tract muscle-infiltrating TCC and required
      nephroureterectomy. All of them had high risk TCC of the bladder and one
      developed distant metastasis. CONCLUSIONS: Patients under abdomino-pelvic RT and
      a prolongued follow-up, can be considered a risk group for developing muscle
      infiltrating TCC. Thus, either micro or macrohaematuria or irritative symptoms
      should lead us to think in this possibility, demanding complete and exhaustive
      study to rule out TCC in all the urothelium.

PMID- 16092680
TI  - [Is it necessary to always treat the relapses of superficial bladder tumour at
      the moment of diagnosis? Preliminary communication].
AB  - OBJECTIVE: To assess the expectant management superficial recurrent bladder
      tumours. MATERIAL AND METHODS: Between Jan 1998 and Dec 2003, 112 patients were
      diagnosed of superficial bladder tumour. 13 patients were observed after the
      diagnosis of tumour relapse until the decision to perform a transurethral
      resection. We analysed the clinical and pathological features. The patients were
      controlled with flexible cystoscopy every 3 months approximately. Of the 13
      patients we count 15 observation events, (2 times in 2 patients). The decision
      between to treat or continue with observation was based in changes of appearance,
      size or number of tumours and presence of hematuria. RESULTS: With a mean age of
      74.6 years (47-91). The mean observation time was 5.76 months (3-71). In the
      group of tumours previous to the observation period, in 12 events (10 patients)
      that means 80% any progression in grade or stage was observed. In the other 3
      events we observed progression in grade and stage in 2 and only stage in 1. In
      any case we observed progression to invasive bladder tumour neither upper urinary
      tract tumour. CONCLUSIONS: Due to the low risk of progression, we believe that
      immediate eradication is not always necessary, thus reducing the adverse impact
      of repeat resections.

PMID- 16092681
TI  - [Foreign bodies in the urethra and bladder: our experience].
AB  - We report the urethra and bladder foreign bodies seen in our department from 1976
      to September 2004. We review the kind of the foreign bodies, the psychological
      profile of the patient, the clinical findings, diagnosis and treatment. We also
      review the literature about this matter.

PMID- 16092682
TI  - [Surgical complications after kidney transplantation. Research based on 185
      cases].
AB  - OBJECTIVE: To analyze the incidence of surgical complications its diagnosis and
      treatment after renal transplantation. METHODS: A retrospective study measuring
      the incidence of surgical complications and reviewing its diagnosis and treatment
      in 185 renal single transplants. RESULTS: 185 transplants, 27% had surgical
      complications. Only one patient lost the graft due to surgical complications and
      there was no associated mortality. Cold ischemia time 20 hours. Double J stenting
      in 19%, under surgeon's opinion. Vascular complications 3.2% (all of them renal
      artery stenosis). Urological complications 6.4%. Perinephric haematoma 7%.
      Lymphocele 4.9%. Peritoneum related complications 4%. Other 4%. The diagnosis was
      clinical and radiological in most of cases. 14% needed any kind of intervention.
      CONCLUSIONS: Our results are similar to those reported in other recent series.
      Only one surgical team involved and the same technique for vascular and vesico
      ureteric anastomosis probably makes lower our complications rate. Early
      postoperative abdominal ultrasonography contributes to the diagnosis of surgical
      complications. The initial treatment approach is the endoscopic-conservative one,
      with exceptions.

PMID- 16092683
TI  - [Endoscopic treatment of pielo-uretheral lithiasis with Holmium-YAG laser. Two
      years of experience].
AB  - OBJECTIVE: To show the efficiency and safety of Holmium laser in the treatment of
      pyeloureteral lithiasis, based on our own experience since the introduction of
      this source of energy in our department. MATERIAL AND METHODS: From January 2002
      to February 2004, we have carried out 198 ureterorenoscopies using Holmium laser
      to treat lithiasis located in the upper urinary tract. In all cases, a previous
      radiological study demonstrated the stone. Follow-up, where the efficacy of the
      treatment was assessed, was done with a scout x-ray after 3-4 weeks. We evaluated
      the localization and features of the lithiasis, technical aspects, results and
      complications of our series. RESULTS: The most common localization of the
      lithiasis was the pelvic ureter (59%), with the number of treated cases in both
      the iliac and lumbar ureter being similar (16%). 70% of the lithiasis had a size
      between 0.5 and 1.5 cm, and 15% showed a diameter bigger than 1.5 cm. In 61.8% of
      cases, laser lithotripsy was carried out under spinal anaesthesia, being the
      average of the pulses used 2532 (confidence interval 95%), using a working power
      of 1 J in all cases. The overall efficacy of the procedure in terms of size and
      localization was 95.5%. The complication rate was scarce (2.19%). CONCLUSIONS:
      Holmium laser lithotripsy is a very effective and safe procedure since in our
      experience it is 95.5% efficient for pyeloureteral lithiasis treatment and has a
      low rate of complications.

PMID- 16092684
TI  - [Acute urinary retention and hematuria secondary to metastatic renal clear-cell
      carcinoma to the penis].
AB  - Renal cell carcinoma have a great capacity of dissemination and have a great
      variety of clinical presentation. We exposed a clinical note of a patient
      diagnosed of renal cell carcinoma who developed hematuria and acute urinary
      retention due to a penis metastasis. Next we review the literature about this
      topic.

PMID- 16092685
TI  - [Xanthogranulomatous pyelonephritis in childhood. A case report].
AB  - Xanthogranulomatous pyelonephritis is an uncommon chronic inflammatory renal
      disorder. Most cases have been described in middle aged women and it is extremely
      rare in children. We report a case of a 4 year old girl who suffered from
      recurrent urinary tract infection and antibiotic therapy resistance. She had low
      growth-rate and palpable left renal mass on examination and was confirmed by
      radiological findings. We performed left kidney partial resection and then
      histological examination showed focal xanthogranulomatous pyelonephritis. The
      focal form of the disease may respond to antibiotic treatment although usually an
      enucleation or partial resection must be performed. In conclusion
      xanthogranulomatous pyelonephritis should be considered in the differential
      diagnosis of a renal mass and recurrent urinary tract infection in childhood.

PMID- 16092686
TI  - [Spontaneous hemorrhage and arterial hypertension as complication of Adrenal
      Pseudocyst. Report of a case].
AB  - Adrenal Pseudocyst are uncommon and asymptomatic tumors. We report an unusual
      case who had previous high blood pressure and acute hemorrhage presented with
      abdominal pain and shock. Diagnosis was made with ultrasonography and computed
      tomography revealed the presence of large retroperitoneal hematoma around the
      superior pole of the left kidney. Urgent surgery was made with a complete
      excision of a 10 cm. tumor with preservation of adrenal tissue and the left
      kidney. Histopathological diagnosis was: Adrenal Pseudocyst. Blood pressure
      normalized after surgery.

PMID- 16092687
TI  - [Hematuria and sharp renal failure as debut of secondary bladder amiloidosis.
      Presentation of a new case and revision of the literature].
AB  - The primary bladder amiloidosis is an uncommon pathology, not existing in the
      world more than 150 published cases, being even more exceptional the secondary
      bladder amiloidosis being described around 25 cases. The secondary bladder
      amiloidosis associates in most from the patients to arthritis reumatoide of long
      evolution. The diagnoses clinical it is difficult, being necessary the
      differential diagnosis with the bladder tumour. The pathological study and
      inmunohistochemics, confirm the diagnosis. We present the case of a patient that
      I debut with frank hematuria, hemodynamic uncertainty and renal inadequacy that
      it required combined treatment, doctor and surgical for the resolution of their
      square.

PMID- 16092688
TI  - [Partial substitution of the ureter using a short segment of the ileum following
      the Monti procedure].
AB  - The partial substitution of the ureter using a pediculated segment of the ileum
      is a technique used to re-establish ureteral transit and preserve the renal unit,
      following the resection of extensive ureteral lesions. Standard surgical
      procedure for an ileoureteroplasty consists of isolating an ileal duct of equal
      or greater length than the ureteral defect and interposing it in the urinary
      tract in an isoperistaltic direction. Monti described a surgical technique that
      allows for the creation of catheterizable stomas in continent urinary diversions,
      using the Mitrofanoff principle. These passageways were created from one or
      several 2.5 cm long ileal sections by means of their detubulization and
      transverse retubulization. The clinical case study presented here corresponds to
      a 57 year-old male with a history of ureteral lithiasis, with a 9 cm stenosis of
      the sacroiliac ureter. He was treated surgically by means of a resection of the
      stenotic ureter and the interposition of a duct made up of 2.5 ileal sections,
      treated in accordance with the Monti procedure. Since this operation, the
      patient's metabolic state has been completely normal. Morphological and
      functional results have also proved totally satisfactory, as the use of image
      techniques have shown.

PMID- 16092689
TI  - [Myofibroblastic tumor of bladder].
AB  - The myofibroblastic tumor, is a mesenchymal benign tumor of exceptional
      character, being its localization but habitual it is the lung; while its
      appearance in the bladder, is exceptional, not existing but of 100 published
      cases, of this tumor type in the bladder. This tumor type that clinic and
      radiologics, behave as a wicked tumor. The pathological diagnosis is complex, due
      to its similarity with the sarcomas, being necessary to appeal to the
      inmunohistochemics for a I diagnose of certainty. The treatment by means of wide
      resection is usually enough not existing any case of metastasis at the present
      time at distance, neither of malignization. We present a new case of this
      neoplasm, carrying out a wide bibliographical revision.

PMID- 16092695
TI  - Build a national network one region at a time.

PMID- 16092694
TI  - Insurers can no longer afford not to share some data.

PMID- 16092696
TI  - Support grows for establishing national clinical trial registry.

PMID- 16092697
TI  - Economically, country mouse does better.

PMID- 16092698
TI  - Turning the corner: momentum shifts toward consumer-directed plans.

PMID- 16092700
TI  - For more and more workers, small pay means small plans.

PMID- 16092699
TI  - Change in thinking for pharmacy benefits in CDHP.

PMID- 16092701
TI  - Is pay for performance: part of the cure or the problem?

PMID- 16092702
TI  - Cost being equal, consumers prefer older drugs.

PMID- 16092703
TI  - Can CDHPs resolve issues raised by age of biologics?

PMID- 16092704
TI  - Efforts to cover the uninsured an opportunity for health plans.

PMID- 16092705
TI  - Premium hikes for 2006 could be lowest in 5 years.

PMID- 16092706
TI  - Computed tomography: reducing the cost and increasing the effectiveness of dental
      implantology.

PMID- 16092707
TI  - Ensuring the credibility of physiological measurements: assessing error
      variability.

PMID- 16092708
TI  - Minimizing sample size when using exploratory factor analysis for measurement.

PMID- 16092709
TI  - The NDNQI-Adapted Index of work satisfaction.
AB  - The valid measurement of nurses' job satisfaction is critical because job
      satisfaction is important for the retention of qualified nurses to provide
      patient care in hospitals. Two studies were conducted to adapt the Stamps Index
      of Work Satisfaction (1997b) to measure work satisfaction at the patient care
      unit level for use by the National Database of Nursing Quality Indicators
      (NDNQI). In Study 1 (n = 918 RNs) exploratory factor analysis of data obtained
      using the NDNQI-Adapted Index replicated the conceptual dimensions of the Stamps
      measure. Associations with scores on Job Enjoyment were evidence that the Index
      measured the intended construct. Using theta, the reliability of the composite
      subscales was .91. The adapted Work Satisfaction subscale scores explained 46% of
      the variance in Job Enjoyment, with each subscale contributing uniquely (p <
      .001). In Study 2 (n = 2277 RNs) confirmatory factor analysis using structural
      equation modeling supported the 7-subscale structure for the Adapted Index (CFI
      [719] = .88; RMR = .05). Replication of associations between scores on the Index
      subscales and Job Enjoyment provided further evidence regarding validity of the
      data, since the Work Satisfaction subscales explained 56% of the variance in Job
      Enjoyment. The feasibility of using an on-line version of the Adapted-Index for
      data collection was demonstrated. The findings from the two studies indicate that
      the adapted Index of Work Satisfaction has a structure similar to the original
      instrument and is a reliable and valid measure of work satisfaction at the
      patient care unit level.

PMID- 16092710
TI  - The Labor Support Questionnaire: development and psychometric analysis.
AB  - Every year approximately 4 million women in the United States experience
      childbirth. This event has been cited as pivotal in a woman's life. Labor support
      is an important part of this experience since it influences the woman's
      classification of the birth experience as positive or negative. Therefore,
      understanding how intrapartum nurses perceive the role of supportive care during
      labor is paramount. The purpose of this study was to develop a reliable and valid
      instrument that measures intrapartum nurses' perceptions concerning the
      importance of professional labor support in their practice. The sample included
      146 intrapartum nurses from Texas. Cronbach's alpha, Pearson's r, and descriptive
      statistics were used for data analysis. Cronbach's alpha for the Labor Support
      Questionnaire (LSQ) was 0.90. Convergent validity with the Caring Behavior
      Inventory was .57 (p < .001). Findings indicated beginning support for the
      reliability and validity of the LSQ. Further development and psychometric testing
      is recommended to ascertain the dimensionality of the LSQ.

PMID- 16092711
TI  - The intragroup conflict scale: development and psychometric properties.
AB  - Managers in health care organizations spend an average of 20% of their time
      dealing with conflict. Hence, a well-developed measure of intragroup conflict is
      needed to assess work environments. The Intragroup Conflict Scale was developed
      to measure views of conflict, perceptions of behavior, and perceptions of
      affective states, that occur in the core process of conflict. The scale was pilot
      tested with a sample of 184 staff nurses and was later used in a study of
      antecedents and effects of intragroup conflict in the nursing unit (n = 141).
      Data from the two studies were merged (n = 325). Using PCA with varimax rotation
      in the analysis of merged data, three factors that explained 69.2% of variance
      were extracted. Factor 1 reflects opposition processes and negative emotion;
      factor 2 reflects trust and freedom of expression; and factor 3 reflects views of
      conflict. Factor loadings ranged from .60 to .88 on factor 1, from .62 to .79 on
      factor 2, and from .69 to .80 on factor 3. Coefficient alpha for the three
      factors were .89 for factor 1, .88 for factor 2, and .79 for factor 3.
      Correlations with existing scales provided support for construct validity. The
      scale has evidence for its reliability and validity, and may have the potential
      to contribute to the understanding of intragroup conflict in organizations. The
      new Intragroup Conflict Scale demonstrates sufficient construct validity to
      warrant its continued evaluation.

PMID- 16092712
TI  - Psychometric properties of the WHOQOL-BREF questionnaire for the Norwegian
      general population.
AB  - In 1994, the World Health Organization Quality of Life (WHOQOL) Group developed
      the procedure (the WHOQOL 100) to measure quality of life in healthy and ill
      persons from diverse cultures. The purpose of this study was to analyze the
      psychometric properties of a 26-item version of the WHOQOL 100, the WHOQOL-BREF,
      when applied to the Norwegian general population. The questionnaire was sent to
      4,000 randomly selected Norwegian citizens aged 19 to 81 years. The response rate
      was 48.5%. Cronbach's alpha ranged from .60 in the social relationships domain to
      .84 in the physical health domain. Factor analysis resulted in a four-component
      solution partly supporting the established domain structure. Multiple regression
      analysis with sex, age, education, cohabitation and self-reported disease as
      independent variables explained 28%, 8%, 4%, and 15% of the variance for the
      physical health, psychological, social relationships and environmental domains,
      respectively. Self-reported disease was the strongest factor. The results appear
      to be promising regarding scaling qualities, discriminative power, and domain
      structure.

PMID- 16092713
TI  - Indoor air and human exposure assessment--needs and approaches.
AB  - The Commission launched on June 9, 2004 the Environment and Health Action Plan to
      reduce diseases caused by a polluted environment. The plan would develop an EU
      system integrating information on the state of the environment, the ecosystem and
      human health. The action plan identifies 13 actions (including an action on
      indoor air quality), which refer to initiatives on how to better understand the
      environment-health link and establish how environmental exposure leads to
      epidemiological effects. The ultimate goal of the proposed "Environment and
      Health Strategy" is to develop an environment and health "cause-effect framework"
      that will provide the necessary information for the development of Community
      policy dealing with sources and the impact pathway of health stressors. The need
      for policy-science interface in the EU guided in the last few years the research
      on indoor air pollution. In particular, the lack of information regarding human
      exposure to air pollutants makes it necessary, in line with the Environment and
      Health Action Plan, to develop targeted strategies to evaluate the impact of
      indoor air pollution on human health. This includes apart from specific
      measurements in selected confined spaces (homes, schools, public buildings,
      etc.), large-scale monitoring campaigns at European level, specifically designed
      to assess indoor and outdoor air quality and personal exposure to pollutants in
      combination with micro-environmental activity patterns. Information from these
      studies will be considered as crucial for a first evaluation of the overall
      situation in indoor environments and the possible sources and source strengths of
      pollutants to which humans are exposed during working, commuting and rest time.
      As a first approach to systematically evaluate the relationship between indoor
      air pollution and human (chronic) exposure to pollutants, we started at the end
      of 2003 with the AIRMEX project (Indoor Air Monitoring and Exposure Assessment
      Study). In the frame of AIRMEX, measuring campaigns in various cities in Southern
      and Central Europe were carried out to estimate indoor/outdoor relationships and
      personal exposure concentrations for selected volatile organic compounds
      (aromatics, carbonyls, terpenoids). In agreement with the overall scope of the
      project, the measuring objects included public buildings (town halls, guild
      halls), schools and kindergartens. Personal exposure measurements were conducted
      with employers and/or teachers working in the selected occupational environments.
      Preliminary results indicate that personal exposure concentrations are higher
      than the indoor/outdoor concentrations. In most cases they are twice as high (or
      even higher) as indoor concentrations and significantly higher than outdoor
      concentrations.

PMID- 16092714
TI  - Health determinants in Europe for indoor and outdoor pollutants from a public
      health and social medicine view.

PMID- 16092715
TI  - Characterization of complex mixtures in urban atmospheres for inhalation exposure
      studies.
AB  - A real-world assessment of the source-to-receptor pathways for ambient
      particulate matter (PM), as opposed to in a laboratory environment, was crucial
      for gaining a better understanding of the types of particles to which people are
      actually exposed in their daily lives, and of the human-health risks for source
      specific PM. However, obtaining scientific evidence linking specific source
      emissions to health responses was not an easy task; ambient PM possesses diverse
      chemical, physical and thermodynamic properties, and is subjected to numerous
      complex atmospheric processes in which source type, source strength, sinks, and
      meteorology interact continuously. Our collaborative PM health research studies
      utilized an integrated approach that employs detailed characterization of ambient
      PM concurrent with inhalation toxicology studies using animal models and
      concentrated fine air particulates (CAPs). Ambient PM2.5 (PM less than 2.5 microm
      in mean aerodynamic diameter) was concentrated with a Harvard fine particle
      concentrator housed in AirCARE1, a unique mobile air research laboratory which
      enables inhalation exposure studies in real-world settings. This paper discusses
      the importance of comprehensive characterization of ambient PM2.5, CAPs and their
      sources, and the associated challenges. In a southwest Detroit community where
      the pediatric asthma rate is about three times the national average, a detailed
      assessment was performed including: characterization of ambient PM2.5 and CAPs;
      identification of major emission sources of PM2.5; and quantification of trace
      elements in lung tissues of laboratory rats that were exposed to CAPs, all in an
      effort to define source-receptor pathways for ambient PM2.5. Our findings to date
      constitute evidence of the retention of ambient urban particulates from local
      combustion sources within animal tissues from short-term exposures, and possible
      associations between the observed health effects and source-specific PM2.5.
      However, a complete understanding of the effects of complex mixtures of air
      pollutants and their toxicological impacts still faces many challenges.

PMID- 16092716
TI  - Atmospheric transformation of diesel emissions.
AB  - This paper reviews the major physical and chemical transformation the primary
      diesel emissions undergo during dispersion and transport in the atmosphere. Since
      diesel emissions contain compounds that are present in other combustion source's
      emissions, their atmospheric transformations are not specific to this source
      category only. The most important chemical reactions of diesel exhaust
      constituents are with OH radicals, followed by ozone, NO3 radicals and light.
      While data now exists concerning the chemical and physical nature and the
      inventory of diesel emissions, our knowledge concerning the products of their
      chemical transformations is still limited. In particular, there is currently very
      little in the literature that addresses the impact of atmospheric transformation
      on the health effects of inhaled diesel exhaust. As an example of such a study,
      the design and the preliminary data obtained from the current project executed
      with the aid of the European Photoreactor (EUPHORE) simulation chamber in
      Valencia, Spain, is discussed.

PMID- 16092717
TI  - Analysis of complex mixtures--cigarette smoke.
AB  - Mainstream cigarette smoke is a complex mixture that is inhaled into the
      respiratory system. The physical characteristics and chemical composition of
      mainstream smoke are reviewed and briefly compared with that of sidestream smoke.
      Special attention is paid to ageing effects and artifact formation during the
      sampling and testing of cigarette smoke, with specific examples of artifact
      formation during sampling discussed (nitrogen dioxide, methyl nitrite, etc.).
      Historically, the generation of cigarette smoke for chemical and biological
      testing has been based on standard smoke generation procedures that are intended
      for product comparisons. More recently, emerging global regulations have called
      for alternative smoke generation methods, with emphasis on results relevant to
      conditions of product use, e.g., estimates of maximum smoke emissions. Strategies
      for establishing such alternative smoke generation methods are discussed and the
      potential effects of alternative smoking conditions on analytical accuracy and
      precision are addressed. Current regulatory requirements that include Hoffmann
      analyte analysis (i.e., constituents reported to be associated with the risks of
      cigarette smoking) are also summarized and the potential effect of alternative
      smoke generation methods on individual constituent yields considered. Finally, a
      limited critique of emerging regulation that relates to mainstream cigarette
      smoke measurements, including a discussion of recent WHO recommendations, is
      offered.

PMID- 16092718
TI  - Biomonitoring of inhaled complex mixtures--ambient air, diesel exhaust and
      cigarette smoke.
AB  - Human biomonitoring comprises the determination of biomarkers in body-fluids,
      cells and tissues. Biomarkers are generally assigned to one of three classes,
      namely, biomarkers of exposure, effect or susceptibility. Since biomarkers
      represent steps in an exposure-disease continuum, their application in
      epidemiological studies ('molecular epidemiology') shows promise. However, to be
      a predictor of disease, a biomarker has to be validated. Validation criteria for
      a biomarker include intrinsic qualities such as specificity, sensitivity,
      knowledge of background in the population, existence of dose-response
      relationships, degree of inter- and intra-individual variability, knowledge of
      the kinetics, confounding and modifying factors. In addition, properties of the
      sampling and analytical procedures are of relevance, including constraints and
      non-invasiveness of sampling, stability of sample as well as simplicity, high
      sensitivity, specificity and speed of the analytical method. It is of particular
      importance to prove by suitable studies that the biomarker of exposure indicates
      the actual exposure, the biomarker of effect strongly predicts the actual risk of
      disease and the biomarker of susceptibility actually modifies the risk.
      Biomonitoring of the exposure to complex mixtures such as polluted ambient air,
      diesel exhaust or tobacco smoke is a particular challenge since these exposures
      have many constituents in common and many people were exposed to more than one of
      these mixtures. Data on the exposure to polycyclic aromatic hydrocarbons (PAH)
      and benzene from ambient air, diesel exhaust and tobacco smoke will be presented.
      In addition, some source-specific biomarkers such as nitro-arenes and nicotine
      metabolites as well as their application in population groups will be discussed.
      The second part of the presentation addresses the application of biomarkers for
      assessing so called 'potentially reduced exposure products' (PREPs). According to
      a recent report of the Institute of Medicine (USA), "reducing risk of disease by
      reducing exposure to tobacco toxicants is feasible" and "surrogate biological
      markers that are associated with tobacco-related diseases could be used to offer
      guidance as to whether or not PREPs are likely to be risk-reducing." In general,
      the same validation criteria apply as discussed above. In addition, it is
      suggested that a panel of biomarkers should be used, representing both smoke
      phases (gas and particulate phase) and the various chemical classes of smoke
      constituents (e.g., carbonyls, benzene, PAH, tobacco-specific nitrosamines,
      aromatic amines). Also, a panel of biomarkers of effect should cover the major
      known adverse effects of smoking (e.g., oxidative stress, inflammatory processes,
      lipid peroxidation, lipometabolic disorders, mutagenic effects). Biomarkers of
      nicotine and carbon monoxide uptake are of interest for evaluating the smoking
      and inhalation behavior, respectively. Finally, suitable study designs for
      evaluating PREPs are discussed. It is concluded that suitable biomarkers for
      assessing the exposure to complex mixtures such as ambient air, diesel exhaust
      and tobacco smoke as well as for evaluating the exposure-reducing properties of
      PREPs are already available. Future efforts should focus on the development and
      validation of biomarkers of effect.

PMID- 16092719
TI  - Overview of inhalation exposure techniques: strengths and weaknesses.
AB  - The vast majority of toxicity studies and risk evaluations deal with single
      chemicals. Due to the growing interest in potential human health risks
      originating from exposure to environmental pollutants or lifestyle-related
      complex chemical mixtures, well thought-out tailor-made mechanistic inhalation
      toxicity studies have been performed. In contrast to the complex mixtures
      potentially encountered from hazardous waste sites, drinking water disinfection
      by-products, natural flavoring complexes or the cumulative intake of food
      additives and pesticide residues, the scientific evaluation of complex airborne
      mixtures, such as acid aerosols, atmospheres produced by combustion or
      thermolysis, e.g. residual oil fly ash (ROFA), diesel and gasoline exhaust, and
      tobacco smoke, or volatile organic chemicals (VOCs) in residential areas, to
      mention but a few, is a daunting challenge for experimental toxicologists. These
      challenges include the controlled in situ generation of exposure atmospheres, the
      compositions of which are often process-determined and metastable. This means
      that volatile agents may partition with liquid aerosols or be adsorbed onto
      surfaces of solid aerosols. Similarly, the nature and composition of test
      atmospheres might change continuously through oxidation and aging of constituents
      or coagulation of particles. This, in turn, poses additional challenges to the
      analytical characterization of such complex test atmospheres, including the
      identification of potential experimental artifacts. Accordingly, highly
      standardized and controlled inhalation studies are required for hazard
      identification of complex mixtures and the results of inhalation studies have to
      be analyzed judiciously due to the great number of experimental variables. These
      variables may be related to technical issues or to the specific features of the
      animal model. Although inhalation exposure of animals mimics human exposure best,
      not all results obtained under such rigorous test conditions might necessarily
      also occur under real-life exposure conditions. In addition, to simulate
      experimentally specific use or exposure patterns may impose a particular
      challenge to traditional approaches in terms of relevant exposure metrics and the
      analytes chosen to characterize exposure atmospheres. This paper addresses major
      developments in the discipline of inhalation toxicology with particular emphasis
      on the state-of-the-art testing of complex mixtures.

PMID- 16092720
TI  - Epithelial and inflammatory responses in the airways of laboratory rats coexposed
      to ozone and biogenic substances: enhancement of toxicant-induced airway injury.
AB  - People are often concurrently exposed to more than one air pollutant whether they
      are in outdoor or indoor environments. Therefore, inhalation studies that are
      designed to examine the toxicity of coexposures to two or more airborne toxicants
      may be more relevant for assessing human health risks than those studies that
      investigate the toxic effects of only one airborne toxicant at a time.
      Furthermore, airborne biogenic substances such as pollens, bacteria, fungi, and
      microbial toxins often coexist with common air pollutants in the ambient air, and
      when inhaled may also cause specific adverse effects on the respiratory tract.
      One such biogenic substance, bacterial endotoxin, is a potent stimulus of airway
      inflammation and is commonly found in domestic, agricultural, and industrial
      settings. Little is known about the interaction of exposures to biogenic
      substances and common air pollutants, such as ozone or airborne particulate
      matter. In the last few years, we have performed a series of in vivo studies
      using laboratory rodents that examined how airway surface epithelial cells are
      altered by coexposure to ozone and a biogenic substance, either bacterial
      endotoxin or a commonly used experimental aeroallergen (ovalbumin). Results from
      these studies indicate that the ozone-induced epithelial and inflammatory
      responses in laboratory rodents may be markedly enhanced by coexposure to an
      inhaled biogenic substance. Conversely, the adverse airway alterations caused by
      exposure to biogenic substances may be enhanced by coexposure to ozone. The
      results from these initial studies have also suggested some of the cellular and
      molecular mechanisms underlying the phenotypic epithelial alterations induced by
      these coexposures. Many more studies are needed to fully elucidate the potential
      risk to human health from coexposure to air pollutants and airborne biogenic
      substances.

PMID- 16092721
TI  - Animal models and their limitations: on the problem of high-to-low dose
      extrapolations following inhalation exposures.
AB  - Inhalation of complex mixtures such as combustion aerosols constitutes a parallel
      and simultaneous exposure of two distinctively different barriers to the body;
      the alveolar type I cells and the rest of the airway air/blood barrier, mainly
      the epithelium of the conducting airways. Exposure of the type I epithelium to
      most solutes leads to a rapid passage into the systemic circulation, and
      activation/deactivation of toxicants will take place mostly in the liver. Because
      of the huge metabolizing capacity of the liver, the dose-response of this
      component of an inhalation exposure is likely to be close to linear over larger
      exposure intervals. In contrast, exposures of the epithelium in the conducting
      airways lead to a slower passage, and in the case of semi-volatile solutes of
      high lipophilicities, a much slower passage into the systemic circulation. The
      result is a highly elevated concentration in the epithelium of the conducting
      airways during absorption, which may either lead directly to a localized
      toxicity, or, provide substrate for activating enzymes present in the airway
      mucosa. However, because of a limited capacity of the airway epithelium in this
      region both to dissolve sparingly soluble inhalants and to metabolize such
      solutes, the local dose response is likely to saturate at rather low exposure
      levels. One important consequence of local saturation in the epithelium of the
      conducting airways, is that inhalation exposures of laboratory animals conducted
      at elevated concentrations and limited time spans, may underestimate the risk in
      humans chronically exposed at relatively low concentrations. The phenomenon could
      be relevant in the etiology of lung cancer as well as inflammatory airway
      disease, where semi-volatile organic toxicants are suspected to contribute
      significantly.

PMID- 16092722
TI  - Genetic aspects of pulmonary responses to inhaled pollutants.
AB  - Air pollution continues to be a major public health concern in industrialized
      cities throughout the world. Recent population and epidemiological studies that
      have associated ozone and particulate exposures with morbidity and mortality
      outcomes underscore the important detrimental effects of these pollutants on the
      lung. Inter-individual variation in human responses to air pollutants suggests
      that some subpopulations are at increased risk to the detrimental effects of
      pollutant exposure, and it has become clear that genetic background is an
      important susceptibility factor. Environmental exposures to inhaled pollutants
      and genetic factors associated with disease risk likely interact in a complex
      fashion that varies from one population to another. The relationships between the
      genetic background and disease risk and severity is often evaluated through
      traditional family-based linkage studies and positional cloning techniques. Case
      control studies based on association of disease or disease subphenotypes with
      candidate genes may have certain advantages over family pedigree studies, and
      have become useful for understanding complex disease phenotypes. This is based in
      part on continued development of quantitative analysis and development of mapping
      technologies. Linkage analyses with genetically standardized animal models are
      useful to identify genetic determinants of host responses to environmental
      stimuli. For example, linkage analyses using inbred mice have identified
      chromosomal segments (quantitative trait loci, QTL) that contain genes that
      control susceptibility to the lung inflammatory and immune dysfunction responses
      to ozone, nitrogen dioxide, zinc oxide, and sulfate-associated particles.
      Candidate genes within the pollutant susceptibility QTLs have been tested for
      proof-of-concept using gene-targeting and overexpression models. Importantly,
      significant homology exists between the human and mouse genomes. Therefore,
      comparative mapping between the human and mouse genomes should yield candidate
      susceptibility genes that may be tested by association studies in humans. The
      combined human studies and mouse modeling will provide important insight to
      understanding genetic factors that contribute to differential susceptibility to
      pollutants in human populations.

PMID- 16092723
TI  - Use of bronchoalveolar lavage to detect respiratory tract toxicity of inhaled
      material.
AB  - The first epithelial surface encountered by inhaled materials is the epithelium
      of the respiratory tract. The epithelium is lined by a fluid (ELF) that can be
      sampled by a saline wash (lavage) of the area of interest. This technique, known
      as bronchoalveolar lavage (BAL), provides a means of sampling a body fluid that
      can provide valuable information on the reaction of the lung to inhaled
      materials. The most common responses measured are indicators of an inflammatory
      response, the most sensitive of which is an influx of neutrophils. In the
      extracellular fluid, levels of beta-glucuronidase activity indicate activation of
      macrophages, and lactate dehydrogenase activity indicates cytotoxicity. Other pro
      and anti-inflammatory soluble factors that can be measured in BAL fluid include
      secretory products of macrophages and epithelial cells, such as tumor necrosis
      factor alpha, fibronectin, interleukin-1, various chemotactic factors (including
      IL-8, MIP-2), growth factors, proteases, and antiproteases. Oxidative stress can
      be measured by the levels of reduced glutathione in ELF, and increased levels of
      alkaline phosphatase indicate increased Type II cell secretions. Allergic
      responses are indicated by increased eosinophils and factors such as histamine
      and arachidonate metabolites in BAL fluid. BAL analysis can be used as a
      complementary technique with more traditional measures of lung injury, such as
      histopathology or radiology. The advantage of BAL analysis is that one can pick
      up early indicators of biochemical changes leading to later morphological changes
      in a disease process. A second advantage is that the BAL fluid analyses are
      quantitative, and dose-response measures can be obtained. In large animals, one
      can do repeated lavages to follow a disease process; in small animals, one can
      use serial sacrifices in similarly exposed rodents to achieve the same goal.
      Research related to the use of BAL fluid analyses to detect lung damage has been
      conducted at the Lovelace Respiratory Research Institute with funding from
      various sources including the US Department of Energy and the US Environmental
      Protection Agency.

PMID- 16092724
TI  - Oxidative DNA modifications.
AB  - Oxidative DNA modifications are frequent in mammalian DNA and have been suggested
      an important mechanism in carcinogenesis, diabetes and ageing. The foundations
      for this suggestion are: Evidence for the importance of oxidative DNA
      modifications in cancer development is: high levels of oxidative lesions in
      cancer tissue; highly conserved and specific DNA repair systems targeting
      oxidative lesions; high levels of oxidative DNA lesions in oxidative DNA repair
      knock-out animals; defective repair of oxidative lesions in cancer-prone progeria
      syndromes; reduced cancer incidence in populations with high dietary antioxidant
      intake; and increased oxidative stress to DNA in tobacco smokers. Conflicting
      evidence for a relation between oxidative stress to DNA and cancer is:
      disagreement about the true levels and occurrence of the oxidative lesions in
      vivo; failure to identify the localization of oxidative lesions in important
      genes, e.g. tumor suppressor and oncogenes; lack of evidence that the oxidative
      lesions induce mutations in vivo; no cancer development in animals knocked-out
      for specific DNA repair enzymes in spite of high tissue levels of oxidative
      lesions; and unchanged cancer rates after antioxidant interventions in large
      clinical controlled and randomized trials. The rate of DNA oxidation has been
      estimated from urinary excretion of repair products and it is evident that if
      these lesions were not repaired, a large part of DNA would be oxidized to a
      degree not compatible with living. The methodologies by which oxidative DNA
      modifications are measured cover a wide and different range, advantages and
      disadvantages will be presented. One particular problem is artificial oxidation,
      and methods to prevent such artifacts will be presented together with results
      from a large interlaboratory standardization program. The methodology by which
      the lesions can be measured is complicated and prone to artifacts during DNA
      isolation, digestion, derivatization and maybe even during the separation
      procedure proper prior to detection. A large effort from 20+ laboratories
      supported by a grant from the EU has reduced artifacts considerably and work
      towards interlaboratory standardization of the methodology is in progress. The
      presently agreed "normal" levels of the most frequent known lesion 8-oxodG is
      about 5 per million dG's in DNA. A comprehensive evaluation of the evidence, from
      chemistry to clinical and epidemiological trials, linking oxidative modifications
      to cancer will be given. Finally, an estimate of the quantitative role oxidative
      DNA modifications play among the multiplicity of other insults is given. While
      there is no question that all of these oxidative mechanisms do exist,
      quantitative data on their importance for the human situation do not exist.
      Prospective human studies that can provide such quantitative data on different
      mechanisms are underway.

PMID- 16092725
TI  - The complexities of an apparently simple lung tumor model: The A/J mouse.
AB  - A simple animal model of tobacco smoke carcinogenesis works as follows: Strain
      A/J mice are exposed for 5 months to tobacco smoke. They are then given a 4-month
      recovery period in air before being killed. Lung surface tumors are counted and
      lung tumor multiplicity (average number of tumors per lung, including non-tumor
      bearing animals) is calculated. Results obtained in four different laboratories
      during the past 8 years have consistently shown significant increases in lung
      tumor multiplicities in tobacco smoke exposed animals. While inhaling to tobacco
      smoke, strain A mice (but not some other strains) fail to gain weight and
      immediately after smoke exposure only have about 75% of control weight; however,
      when removed into air, they regain weight rapidly up to control levels. The
      counting of surface tumors only may occasionally underestimate total number of
      lung tumors and thus yield false negatives. At the end of the experiment, the
      mice are 1-year old and about 80% of the tumors are adenomas, the remainder
      adenomas with carcinomatous foci or adenocarcinomas. Tobacco smoke does not
      increase the percentage of adenocarcinomas. Studies with filtered tobacco smoke
      have suggested that benzo(a)pyrene or tobacco smoke-specific nitrosamines cannot
      account for lung carcinogenesis in mice; the most likely single agent to cause
      lung tumors is 1,3-butadiene. A major disadvantage of the assay is its low
      statistical power. While it is easy to detect a 70-100% decrease in lung tumor
      multiplicity caused by a chemopreventive agent using group sizes of 20-30
      animals, the detection of smaller reductions (20-50%) would require group sizes
      in the hundreds. From all available evidence it must be concluded that the
      complex mixture of tobacco smoke, a known human carcinogen, is a rather weak
      rodent carcinogen.

PMID- 16092726
TI  - In vitro studies: what is their role in toxicology?
AB  - Many epidemiology studies have reported associations between inhaled
      environmental pollutants, especially particles, and mortality or morbidity.
      Despite these impressive associations, fundamental uncertainties exist as to the
      underlying pathophysiological mechanisms responsible for mortality or morbidity
      following exposure to air pollutants. In vitro toxicology provides a powerful
      approach to describe these mechanisms at the cellular, biochemical, and molecular
      level. This manuscript will describe some advantages and limitations of in vitro
      toxicology studies in comparison with epidemiology studies, and human and animal
      exposure studies. A recent example will also be presented which demonstrates that
      the response of cultured cells to air pollution particles is similar to the
      response seen following in vivo exposure to the same particles. This coherence
      between an in vivo and in vitro response provides relevance to additional in
      vitro studies that characterize the mechanisms by which these particles cause
      adverse health effects.

PMID- 16092727
TI  - Metabolism and bioactivation of toxicants in the lung. The in vitro cellular
      approach.
AB  - Lung is a target organ for the toxicity of inhalated compounds. The respiratory
      tract is frequently exposed to elevated concentrations of these compounds and
      become the primary target site for toxicity. Occupational, accidental or
      prolonged exposure to a great variety of chemicals may result in acute or delayed
      injury to cells of the respiratory tract. Nevertheless, lung has a significant
      capability of biotransforming such compounds with the aim of reducing its
      potential toxicity. In some instances, the biotransformation of a given compound
      can result in the generation of more reactive, and frequently more toxic,
      metabolites. Indeed, lung tissue is known to activate pro-carcinogens (i.e.
      polycyclic aromatic hydrocarbons or N-nitrosamines) into more reactive
      intermediates that easily form DNA adducts. Lungs express several enzymes
      involved in the metabolising of xenobiotics. Among them, cytochrome P450 enzymes
      are major players in the oxidative metabolism as well metabolic bioactivation of
      many organic toxicants, including pro-carcinogens. Xenobiotic-metabolising P450
      enzymes are expressed in bronchial and bronchiolar epithelium, Clara cells, type
      II pneumocytes, and alveolar macrophages Individual CYP isoforms have different
      patterns of localisation within pulmonary tissue. With the aid of sensitive
      techniques (i.e. reverse transcriptase-polymerase chain reaction, RT-PCR) it has
      become possible to detect CYP1A1, CYP1B1, CYP2A6, CYP2B6, CYP2E1 and CYP3A5 mRNAs
      in lung cells. Less conclusive results have been obtained concerning CYP2Cs,
      CYP2D6 and CYP3A4. CYP3A5 protein appears to be widely present in all lung
      samples and is localised in the ciliated and mucous cells of the bronchial wall,
      bronchial glands, bronchiolar ciliated epithelium and in type I and type II
      alveolar epithelium. Lung cells also express Phase II enzymes such as epoxide
      hydrolase, UGT1A (glucuronyl transferase) and GST-P1 (glutathione S-transferase),
      which largely act as detoxifying enzymes. A key question concerning organ
      specific chemical toxicity is whether the actual target has the capacity to
      activate (or efficiently inactivate) chemicals. Results of several studies
      indicate that the different xenobiotic-metabolising CYPs, present in the human
      lung and lung-derived cell lines, likely contribute to in situ activation of
      pulmonary toxins, among them, pro-carcinogens. Some CYPs, in particular CYP1A,
      are polymorphic and inducible. Interindividual differences in the expression of
      these CYPs may explain the different risk of developing lung toxicity (possibly
      cancer), by agents that require metabolic activation. Few cell lines, principally
      A549, have been used with variable success as an experimental model for
      investigating the mechanisms of toxicity. Although RT-PCR analysis has evidenced
      the presence of the major human pulmonary CYP mRNAs, the measurable P450 specific
      activities are, however, far below those present in human lungs. Detection of the
      toxicity elicited by reactive metabolites requires the use of metabolically
      competent cells; consequently, better performing cells are needed to ensure
      realistic in vitro prediction of toxicity. Genetic manipulation of lung-derived
      cells allowing them to re-express key biotransformation enzymes appear to be a
      promising strategy to improve their functionality and metabolic performance.

PMID- 16092728
TI  - The detection of genotoxic activity and the quantitative and qualitative
      assessment of the consequences of exposures.
AB  - A wide range of assays are now available which enable the effective detection of
      the mutagenic (the induction of gene and chromosomal changes) and more generally
      genotoxic (cellular interactions such as DNA lesion formation) activity of
      individual chemicals and mixtures. However, when genotoxic activity has been
      detected and human exposure occurs the critical questions relate to the
      qualitative and quantitative activity of the agent and the parameters such as
      routes of exposure, target organs and metabolism. Of major importance in hazard
      and risk estimation is the nature of the dose response relationship of each
      chemical and their potential interactions in mixtures. In this paper, we
      illustrate the methods available to produce quantitative and qualitative data in
      vitro using the micronucleus assay (as a measure of chromosomal structural and
      numerical mutations) and the HPRT assay (as a measure of induced gene and point
      mutations) and the current limitations (such as the large numbers of animals
      required) for obtaining such information in vivo. We recommend that in vivo
      studies should primarily focus upon confirmatory mechanistic analysis. For
      individual chemicals, profiles of the base changes induced can be obtained using
      the HPRT gene mutation assay and comparisons produced both in vitro and in vivo
      and thus allow identification of mechanistic differences between different modes
      of exposure.

PMID- 16092729
TI  - Direct exposure methods for testing native atmospheres.
AB  - In vitro studies of adverse cellular effects induced by inhalable substances face
      a number of problems due to the difficulties in exposing cultured cells of the
      respiratory tract directly to test atmospheres composed of complex gases and
      particulate compounds. This paper discusses the characteristics of in vitro work
      and summarizes the use of different in vitro technologies to determine the
      adverse effects of inhaled pollutants. The exposure of cells to test atmospheres
      requires accurate control of the pollutant levels, as well as the close contact
      of cells and gas without interfering with the medium. Systems which rely on the
      solution of the gas in the medium overlay do not resemble the exposure conditions
      in vivo, and may not be suitable for studying, for example, the effects of poorly
      soluble gases. Exposure to gases or complex mixtures can be performed with roller
      bottles or flasks on rotating and rocking platforms and, using these techniques,
      the cells are periodically exposed to the test atmosphere. However, the most
      promising approach is based on a biphasic cell culture technique, where cells are
      grown on microporous membranes at an air-liquid interface. Here the cells are
      nutrified from the basal side of the membrane whilst the apical part with the
      cultivated cells is in direct contact with the test atmosphere. Based on this
      culture technique, different exposure systems have been developed and these are
      described and discussed. Exposure of cells from the respiratory tract to gases or
      particles is responsible for cell injury or cell activation associated with an
      overexpression of mRNA and the release of bioactive mediators. Therefore, in
      vitro studies using such a strategy, in combination with relevant and efficient
      exposure devices, open up new ways to test native complex gases and aerosols.
      Furthermore, such an experimental approach is not only suitable for cultivated
      cells, but it can also be used for exposing bacteria to inhalable test compounds.
      It is possible to analyze the mutagenic potency of in- and outdoor pollutants and
      several attempts have been made to determine the induction of revertants in a
      modified Ames assay after exposure to single gases or complex mixtures.

PMID- 16092730
TI  - Designing in vitro assay systems for hazard characterization. basic strategies
      and related technical issues.
AB  - Adverse effects of chemicals on humans are typically assessed following four
      steps: hazard identification, hazard characterization, exposure assessment and
      risk characterization. Hazard characterization is defined as the qualitative
      and/or quantitative evaluation of the nature of the adverse effects associated
      with biological, chemical and physical agents of interest. For chemical agents,
      hazard characterization is based on a series of in vitro and/or in vivo data
      obtained from mechanistic, kinetic and dose-response studies on the agent of
      concern, which are analyzed and integrated for extrapolation to eventually match
      human conditions. Thus, an accurate experimental design and the development of
      test methods capable of generating data relevant to hazard characterization are
      essential for the useful risk assessment of chemicals, including inhaled
      materials. It should, however, be stressed that hazard characterization has
      widely been limited to single chemicals. The hazard characterization of airborne
      mixtures therefore poses a new problem in toxicology, which calls for a novel
      approach to its scientific assessment. During the last three decades, a number of
      epidemiological and experimental studies have been conducted focusing on two
      kinds of inhaled complex mixtures, namely cigarette smoke and diesel exhausts. A
      new approach to the assessment of airborne complex mixtures may be elaborated
      through the appropriate, combined use of the findings of such studies. In this
      context, the present review article is intended to illustrate some basic
      strategies for and technical issues related to the hazard characterization of
      inhaled complex mixtures, thereby taking up representative epidemiological and
      experimental data from published papers on tobacco smoke.

PMID- 16092731
TI  - In vitro versus in vivo exposure to combustion emissions.
AB  - Defining the key components of a potentially hazardous aerosol mixture, whether
      at the level of source contributions or specific physical or chemical
      constituents, is a challenging but important problem. From the economic,
      efficiency, and ethical points of view, in vitro techniques have considerable
      appeal for these types of studies. However, no in vitro technique will ever have
      the complexity of the whole animal or person. Even for lung-specific endpoints,
      inhalation of aerosol mixtures by a living animal has the potential to induce
      systemic effects such as recruitment of inflammatory cells and neurogenic effects
      that can secondarily affect the lung, as well as local respiratory system
      responses such as cytokine production, oxidant stress, and cell death. Recent
      studies also demonstrate the potential for the inhaled materials to cause diverse
      systemic effects, which are not easily modeled in vitro. To evaluate the effects
      of aerosol toxicants on lung cells, various in vitro testing techniques have been
      developed. These methods differ in the cell types used (human or other, primary
      cells or transformed cell lines, epithelial or other), the exposure method
      (suspension of collected materials, exposure of conventional cultures to
      aerosols, or air-liquid interface exposures), and the toxicological endpoints
      assessed (cell viability, cytokine production, oxidant stress, cell type-specific
      function). Because these studies may have implications for regulatory decisions,
      it is critical that any in vitro screening process of comparative toxicology be
      validated by comparisons with the effects in animal models, and where possible,
      by controlled human exposures. This article discusses relevant parallels and
      discrepancies between exposures of cells and living animals.

PMID- 16092732
TI  - Experimental Assessment of the Toxicological Effects of Inhaled Complex Mixtures
      on the Respiratory System, 23-25 April 2005, Barcelona, Spain. Summary and
      conclusions of the review committee.

PMID- 16092733
TI  - Infectious diseases of the 21st century and nursing care.

PMID- 16092734
TI  - Chlamydia: A major health threat to adolescents and young adults.
AB  - Sexually transmitted diseases (STDs) constitute a major health burden in the
      United States, causing a number of health problems. Of the top 10 infections
      reported to the Centers for Disease Control and Prevention (CDC), five were STDs-
      chlamydia, gonorrhea, AIDS, syphilis, and hepatitis B. Chlamydia trachomatis
      infections are among the most prevalent of all STDs, and is the most common
      sexually transmitted bacterial infection in the United States. The CDC estimates
      that about four million acute infections occur each year. The number of cases
      that are reported to the CDC has increased every year since 1995. The highest
      incidence of Chlamydia is in teens and young adults from the ages of 15 to 25
      years. It is prevalent in lower socioeconomic groups and large urban populations,
      particularly African Americans. This major health problem is a serious threat to
      teens and young adults, both male and female, but particularly African Americans.
      This paper addresses this major health problem by providing a brief overview of
      STDs, and discusses the most common sexually transmitted disease that women
      experience--Chlamydia. The discussion will include an overview, prevalence,
      pathophysiology, diagnosis, treatment, and screening for Chlamydia and
      observations from research.

PMID- 16092735
TI  - HIV risk behaviors in African American males.
AB  - Human immunodeficiency virus/acquired immune syndrome (HIV/AIDS) infection is the
      fifth leading cause of death for people who are 25-44 years in the United States,
      and is the leading cause of death for African American men ages 35-44. The
      incidence rates for HIV among African Americans are steadily increasing, despite
      wide-spread campaigns to educate the public about the disease. The purpose of
      this article is to review the epidemiology and statistics related to HIV/AIDS, as
      well as changes in the epidemic among African American males. A review of the
      literature was conducted which specifically focused on HIV risk behaviors,
      changing patterns of behavior, and risk modification among African American
      males. Opportunities for future research are also detailed.

PMID- 16092736
TI  - Nurse practitioner/physician assistant education and the management of HCV.
AB  - In this article, the authors discuss the consequences of the 911 attack on the
      United States and the concomitant increase in the noted prevalence of Hepatitis C
      Virus due to the presence of the virus in the blood donors. The authors discuss
      the background and consequences of infection with the virus, epidemiology,
      impetus for curricula development, curricular outcomes, curricula modules, and
      HCV case management for nurse practitioners (NPs) and physician assistants (PAs).

PMID- 16092737
TI  - Herpes Simplex Type 2 Virus: a new horizon.
AB  - Genital herpes or Herpes Simplex Type 2 Virus (HSC-2) is an incurable, venerable
      disease. Genital herpes infects more than 1 of 5 adolescents and adults according
      to the Center for Disease Control. Many people do not know that they have it and
      are not aware that they may be spreading it to others. Treatment and management
      of herpes simplex virus has been through pharmacotherapy and patient education.
      Recent studies have emerged identifying a vaccine for herpes simplex virus. The
      vaccine has thus far proven to be effective for women. Pending further
      investigation the target population is young adolescent girls. The implications
      of the vaccine for future treatment and management of other sexually transmitted
      infections need to be explored.

PMID- 16092738
TI  - Of models and methods: our analytic armamentarium applied to methicillin
      resistant Staphylococcus aureus.

PMID- 16092739
TI  - Use of stochastic epidemic modeling to quantify transmission rates of
      colonization with methicillin-resistant Staphylococcus aureus in an intensive
      care unit.
AB  - OBJECTIVE: To consider statistical methods for estimating transmission rates for
      colonization of patients with methicillin-resistant Staphylococcus aureus (MRSA)
      in an intensive care unit (ICU) from three different sources: background
      contamination, non-isolated patients, and isolated patients. METHODS: We
      developed statistical methods that allowed for the analysis of interval-censored,
      routine surveillance data and extended the general epidemic model for the flow of
      patients through the ICU. RESULTS: Within this ICU, the rate of transmission to
      susceptible patients from a background source of MRSA (0.0092 case per day; 95%
      confidence interval [CI95], 0.0062-0.0126) is approximately double the rate of
      transmission from a non-isolated patient (0.0052 case per day; CI95, 0.0013
      0.0096) and six times the rate of transmission from an isolated patient (0.0015
      case per day; CI95, 0.0001-0.0043). We used the methodology to investigate
      whether transmission rates vary with workload. CONCLUSION: Our methodology has
      general application to infection by and transmission of pathogens in a hospital
      setting and is appropriate for quantifying the effect of infection control
      interventions.

PMID- 16092740
TI  - Modeling transmission of methicillin-resistant Staphylococcus aureus among
      patients admitted to a hospital.
AB  - OBJECTIVE: To determine the impact of the screening test, nursing workload,
      handwashing rates, and dependence of handwashing on risk level of patient visit
      on methicillin-resistant Staphylococcus aureus (MRSA) transmission among
      hospitalized patients. SETTING: General medical ward. METHODS: Monte Carlo
      simulation was used to model MRSA transmission (median rate per 1,000 patient
      days). Visits by healthcare workers (HCWs) to patients were simulated, and MRSA
      was assumed to be transmitted among patients via HCWs. RESULTS: The transmission
      rate was reduced from 0.89 to 0.56 by the combination of increasing the
      sensitivity of the screening test from 80% to 99% and being able to report
      results in 1 day instead of 4 days. Reducing the patient-to-nurse ratio from 4.3
      in the day and 6.8 at night to 3.8 and 5.7, respectively, reduced the number of
      nosocomial infections from 0.89 to 0.85; reducing the ratio to 1 and 1,
      respectively, further reduced the number of nosocomial infections to 0.32.
      Increases in handwashing rates by 0%, 10%, and 20% for high-risk visits yielded
      reductions in nosocomial infections similar to those yielded by increases in
      handwashing rates for all visits (0.89, 0.36, and 0.24, respectively). Screening
      all patients for MRSA at admission reduced the transmission rate to 0.81 per
      1,000 patient-days from 1.37 if no patients were screened. CONCLUSION: Within the
      ranges of parameters studied, the most effective strategies for reducing the rate
      of MRSA transmission were increasing the handwashing rates for visits involving
      contact with skin or bodily fluid and screening patients for MRSA at admission.

PMID- 16092741
TI  - Eradication of methicillin-resistant Staphylococcus aureus from a neonatal
      intensive care unit by active surveillance and aggressive infection control
      measures.
AB  - OBJECTIVES: To describe an outbreak of hospital-acquired MRSA in a NICU and to
      identify the risk factors for, outcomes of, and interventions that eliminated it.
      SETTING: An 18-bed, level III-IV NICU in a community hospital. METHODS:
      Interventions to control MRSA included active surveillance, aggressive contact
      isolation, and cohorting and de-colonization of infants and HCWs with MRSA. A
      case-control study was performed to compare infants with and without MRSA.
      RESULTS: A cluster of 6 cases of MRSA infection between September and October
      2001 represented an increased attack rate of 21.2% compared with 5.3% in the
      previous months. Active surveillance identified unsuspected MRSA colonization in
      6 (21.4%) of 28 patients and 6 (5.5%) of 110 HCWs screened. They were all
      successfully decolonized. There was an increased risk of MRSA colonization and
      infection among infants with low birth weight or younger gestational age.
      Multiple gestation was associated with an increased risk of colonization (OR,
      37.5; CI95, 3.9-363.1) and infection (OR, 5.36; CI95, 1.37-20.96). Gavage feeding
      (OR, 10.33; CI95, 1.28-83.37) and intubation (OR, 5.97; CI95, 1.22-29.31) were
      associated with increased risk of infection. Infants with MRSA infection had a
      significantly longer hospital stay than infants without MRSA (51.83 vs 21.46
      days; P = .003). Rep-PCR with mec typing and PVL analysis confirmed the presence
      of a single common strain of hospital-acquired MRSA. CONCLUSION: Active
      surveillance, aggressive implementation of contact isolation, cohorting, and
      decolonization effectively eradicated MRSA from the NICU for 2 1/2 years
      following the outbreak.

PMID- 16092742
TI  - Staphylococcus aureus colonization and the risk of infection in critically ill
      patients.
AB  - OBJECTIVE: To evaluate the relationship between Staphylococcus aureus nasal and
      tracheal colonization and infection in medical intensive care unit (MICU)
      patients. The primary outcome was the incidence of S. aureus infection in
      colonized versus non-colonized patients. DESIGN: Prospective, observational
      cohort study. Patients admitted to the MICU during the study period were screened
      for S. aureus nasal and tracheal colonization by culture and a PCR assay twice
      weekly. Demographic, clinical, and microbiologic data were collected in the MICU
      and for 30 days after discharge. PFGE and antibiotic susceptibility testing were
      performed on all S. aureus nasal, tracheal, and clinical isolates. RESULTS:
      Twenty-three percent of patients (47 of 208) were nasally colonized with S.
      aureus. Twenty-four percent of these patients developed S. aureus infections
      versus 2% of non-colonized patients (P < .01). Nine of 11 patients with both
      nasal colonization and infection were infected by their colonizing strain. Two of
      47 nasally colonized patients developed an infection with a different strain of
      S. aureus. Fifty-three percent of intubated patients with nasal colonization (10
      of 19) had tracheal colonization with S. aureus as opposed to 4.9% of intubated,
      non-colonized patients (3 of 61) (P < .01). Parenteral antibiotics were
      ineffective at clearing nasal colonization. PCR detected S. aureus colonization
      (nasal and tracheal) within 6.5 hours with a sensitivity of 83% and a specificity
      of 99%. CONCLUSIONS: The incidence of S. aureus infection was significantly
      elevated in nasally colonized MICU patients. Techniques to rapidly detect
      colonization in this population may make targeted topical prevention strategies
      feasible.

PMID- 16092743
TI  - Methicillin-resistant Staphylococcus aureus carriage among patients after
      hospital discharge.
AB  - BACKGROUND AND OBJECTIVE: At the University Medical Center Utrecht (UMCU), follow
      up implies an inventory of risk factors and screening for MRSA colonization among
      all MRSA-positive patients for at least 6 months. If risk factors or positive
      cultures persist or re-emerge, longer follow-up is indicated and isolation at
      readmission. This study investigated how long MRSA-positive patients remained
      colonized after hospital discharge and which risk factors were important.
      Furthermore, the results of eradication therapy were evaluated. DESIGN: All
      patients who were positive for MRSA at the UMCU between January 1991 and January
      2001 were analyzed regarding carriage state, presence of risk factors for
      prolonged carriage of Staphylococcus aureus, and eradication treatment. RESULTS:
      A total of 135 patients were included in the study. The median follow-up time was
      1.2 years. Eighteen percent of the patients were dismissed from follow-up 1 year
      after discharge. Only 5 patients were dismissed after 6 months. Among patients
      with no risk factors, eradication treatment was effective for 95% within 1 year.
      Among patients with persistent risk factors, treatment was effective for 89%
      within 2 years. CONCLUSIONS: Based on these findings, eradication therapy should
      be prescribed for all MRSA carriers, independent of the presence of risk factors.
      MRSA-positive patients should be evaluated for 6 months for the presence of risk
      factors and MRSA carriage. Screening for risk factors is important because
      intermittent MRSA carriage was found in a significant number of our patients.
      Patients with negative MRSA cultures and without risk factors for 12 months can
      be safely dismissed from follow-up.

PMID- 16092744
TI  - Importance of control group selection for evaluating antimicrobial use as a risk
      factor for methicillin-resistant Staphylococcus aureus bacteremia.
AB  - OBJECTIVE: We investigated the importance of control group selection during an
      evaluation of antimicrobial use as a risk factor for methicillin-resistant
      Staphylococcus aureus (MRSA) bacteremia at our institution. METHODS: We performed
      a case-control study. A case was defined as any patient admitted between January
      1997 and May 2001 who developed nosocomial MRSA bacteremia. We used two control
      groups; control group I consisted of patients with nosocomial methicillin
      susceptible S. aureus (MSSA) bacteremia and control group II included only
      patients without bacteremia. We matched control-patients to case-patients using
      age, gender, time at risk, and hospital ward. Data collected on all patients
      included demographics, comorbidities, antibiotic use, time at risk, length of
      stay, severity of illness, and outcome. RESULTS: We evaluated 63 patients (21 in
      each group). The three groups were well matched regarding age, gender, underlying
      diseases, and severity of illness. Patients in the MRSA group were more likely to
      have received a fluoroquinolone and had a higher mean number of days of
      fluoroquinolone use than did patients in the MSSA group (P = .027 and P = .015,
      respectively). However, all measures of fluoroquinolone use were similar for case
      patients and for control-patients who did not have nosocomial bloodstream
      infection. CONCLUSIONS: Control group selection is important in evaluating
      antimicrobial use as a risk factor for MRSA bacteremia. Using control-patients
      infected with MSSA, rather than uninfected control-patients, may overestimate the
      association between antimicrobial use and MRSA infection.

PMID- 16092745
TI  - Use of strain typing data to estimate bacterial transmission rates in healthcare
      settings.
AB  - OBJECTIVE: To create an affordable and accurate method for continuously
      monitoring bacterial transmission rates in healthcare settings. DESIGN: We
      present a discrete simulation model that relies on the relationship between in
      hospital transmission rates and strain diversity. We also present a proof of
      concept application of this model to a prospective molecular epidemiology data
      set to estimate transmission rates for Pseudomonas aeruginosa and Staphylococcus
      aureus. SETTING: Inpatient units of an academic referral center. PATIENTS: All
      inpatients with nosocomial infections. INTERVENTION: Mathematical model to
      estimate transmission rates. RESULTS: Maximum likelihood estimates for
      transmission rates of these two species on different hospital units ranged from 0
      to 0.36 transmission event per colonized patient per day. CONCLUSIONS: This
      approach is feasible, although estimates of transmission rates based solely on
      strain typed clinical cultures may be too imprecise for routine use in infection
      control. A modest level of surveillance sampling substantially improves the
      estimation accuracy.

PMID- 16092746
TI  - Control of vancomycin-resistant enterococci in the neonatal intensive care unit.
AB  - BACKGROUND AND OBJECTIVE: Multidrug-resistant organisms (MDROs), such as
      vancomycin-resistant enterococci (VRE), cause serious infections, especially
      among high-risk patients in NICUs. When VRE was introduced and transmitted in our
      NICU despite recommended infection control practices, we instituted active
      surveillance cultures to determine their efficacy in detecting and controlling
      spread of VRE among high-risk infants. METHODS: Active surveillance cultures,
      other infection control measures, and a mandatory in-service education module on
      preventing MDRO transmission were implemented. Cultures were performed on NICU
      admission and then weekly during their stay. Molecular DNA fingerprinting of VRE
      isolates facilitated targeting efforts to eliminate clonal spread of VRE.
      Repetitive sequence PCR (rep-PCR)-based DNA fingerprinting was used to compare
      isolates recovered from patients with VRE infection or colonization.
      Environmental VRE cultures were performed around VRE-colonized or -infected
      patients. DNA fingerprints were prepared from the products of rep-PCR
      amplification and analyzed using software to determine strain genetic
      relatedness. RESULTS: Active surveillance cultures identified 65 patients with
      VRE colonization or infection among 1,820 admitted to the NICU. Rep-PCR performed
      on 60 VRE isolates identified 3 clusters. Cluster 1 included isolates from 21
      patients and 4 isolates from the environment of the index patient. Clusters 2 and
      3 included isolates from 23 and 3 patients, respectively. Similarity coefficients
      among the members of each cluster were 95% or greater. CONCLUSIONS: Control of
      transmission of multi-clonal VRE strains was achieved. Active surveillance
      cultures, together with implementation of other infection control measures,
      combined with rep-PCR DNA fingerprinting were instrumental in controlling VRE
      transmission in our NICU.

PMID- 16092747
TI  - Reduction in nosocomial transmission of drug-resistant bacteria after
      introduction of an alcohol-based handrub.
AB  - OBJECTIVE: To assess quantitatively the clinical impact of using an alcohol-based
      handrub (ABHR) in the hospital environment, measuring impact as the incidence of
      new, nosocomial isolates of drug-resistant organisms. DESIGN: An observational
      survey from 1998 to 2003 comparing the first 3 years of no ABHR use with the 3
      years following, when an ABHR was provided for hand hygiene. SETTING: An inner
      city, tertiary-care medical center. INTERVENTION: At baseline, an antimicrobial
      soap with 0.3% triclosan was provided for staff hand hygiene. The intervention
      was placement in all inpatient and all outpatient clinic rooms of wall-mounted
      dispensers of an ABHR with 62.5% ethyl alcohol. Data were collected on change in
      the incidence of three drug-resistant bacteria. RESULTS: During the 6 years of
      the survey, all new, nosocomially acquired isolates of methicillin-resistant
      Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and
      Clostridium difficile-associated diarrhea were recorded. On comparison of the
      first 3 years with the final 3 years, there was a 21% decrease in new,
      nosocomially acquired MRSA (90 to 71 isolates per year; P = .01) and a 41%
      decrease in VRE (41 to 24 isolates per year; P < .001). The incidence of new
      isolates of C. difficile was essentially unchanged. CONCLUSION: In the 3 years
      following implementation of an ABHR, this hospital experienced the value of
      reductions in the incidence of nosocomially acquired drug-resistant bacteria.
      These reductions provide clinical validation of the recent CDC recommendation
      that ABHRs be the primary choice for hand decontamination.

PMID- 16092748
TI  - Risk factors for nosocomial infective endocarditis in patients with methicillin
      resistant Staphylococcus aureus bacteremia.
AB  - BACKGROUND AND OBJECTIVE: Nosocomial infections caused by methicillin-resistant
      Staphylococcus aureus (MRSA) are increasing. Only a few studies of MRSA infective
      endocarditis have been conducted, and none have reported its risk factors. We
      sought to determine the host-related risk factors for infective endocarditis in
      patients with nosocomial MRSA bacteremia. SETTING: A 2,000-bed, university
      affiliated, tertiary-care hospital. PATIENTS: Thirty-one patients with nosocomial
      MRSA infective endocarditis between October 1996 and May 2003. DESIGN: A
      retrospective chart review was conducted. Data were compared with those from a
      control group of patients with nosocomial MRSA bacteremia. Logistic regression
      was used to identify independent risk factors for nosocomial infective
      endocarditis. RESULTS: Compared with patients who had nosocomial MRSA bacteremia
      and no infective endocarditis, patients who had infective endocarditis had a
      higher incidence of chronic liver disease and a lower incidence of
      immunodeficiency. The risk of developing infective endocarditis was approximately
      10% for patients with nosocomial MRSA bacteremia. CONCLUSION: Patients with MRSA
      bacteremia and underlying chronic liver disease were prone to infective
      endocarditis.

PMID- 16092749
TI  - Catheter-related vancomycin-resistant Enterococcus faecium bacteremia: clinical
      and molecular epidemiology.
AB  - OBJECTIVE: To study the clinical and molecular epidemiology of vancomycin
      resistant Enterococcus faecium organisms causing catheter-related bacteremia in
      patients with cancer. DESIGN: Retrospective case-control study. SETTING:
      University of Texas M. D. Anderson Cancer Center, a tertiary-care hospital in
      Houston, Texas. PATIENTS: Case-patients were patients with cancer who had
      catheter-related vancomycin-resistant E. faecium bacteremia and control-patients
      were patients with cancer and vancomycin-resistant E. faecium gastrointestinal
      colonization without infection. RESULTS: Ten case-patients with catheter-related
      vancomycin-resistant E. faecium bacteremia were compared with 30 control-patients
      with gastrointestinal colonization by vancomycin-resistant E. faecium. Patients
      with catheter-related vancomycin-resistant E. faecium bacteremia were more likely
      to have required mechanical ventilation (P < .01), received total parenteral
      nutrition (P < .01), and had polyurethane catheters (P < .01) inserted in the
      femoral vein (P = .01). With the use of pulsed-field gel electrophoresis, 4 of
      the 10 catheter-related vancomycin-resistant E. faecium bacteremia isolates were
      genetically indistinguishable, whereas only 2 of the 30 control vancomycin
      resistant E. faecium isolates displayed this same DNA pattern (P = .03).
      CONCLUSION: This study suggests that catheter-related vancomycin-resistant E.
      faecium bacteremia occurs more frequently in patients who receive total
      parenteral nutrition, mechanical ventilation, and femoral catheters.

PMID- 16092750
TI  - Mupirocin for controlling methicillin-resistant Staphylococcus aureus: lessons
      from a decade of use at a university hospital.
AB  - BACKGROUND: From 1990 to 1995 at Hospital Universitario Clementino Fraga Filho,
      patients colonized or infected with methicillin-resistant Staphylococcus aureus
      (MRSA) were treated with mupirocin to eliminate MRSA carriage. In 1995, 65% of
      MRSA patients at this hospital had mupirocin-resistant isolates. Starting in
      1996, mupirocin use was restricted to patients colonized, but not infected, with
      MRSA. OBJECTIVES: To describe the use of mupirocin for controlling MRSA over a
      decade and to analyze the molecular epidemiology of mupirocin-resistant MRSA
      infections at this hospital. SETTING: A 490-bed, tertiary-care university
      hospital. METHODS: The incidence densities of patients with MRSA and acquisition
      of mupirocin by the hospital were calculated for the period 1992-2001. S. aureus
      isolates from 1999-2000 were analyzed by pulsed-field gel electrophoresis.
      Mupirocin-resistant MRSA isolates from 1994-1995 and 1999-2000 were analyzed for
      ileS-2 gene background polymorphisms. RESULTS: The incidence density of MRSA
      patients increased slightly over time, whereas the purchase of mupirocin
      decreased dramatically. Mupirocin-resistant MRSA infections decreased from 65% in
      1994-1995 to 15% in 1999-2000. The MRSA Brazilian clone, detected in 1992, was
      still highly prevalent. The same ileS-2 encoding plasmid found in 1994-1995
      persisted in three identical MRSA isolates from 1999-2000 belonging to the
      Brazilian clone. CONCLUSIONS: After mupirocin use decreased, the ileS-2 encoding
      plasmid persisted in only a few Brazilian clone isolates. Our data on mupirocin
      resistant MRSA incidence and mupirocin use strongly suggested that restricted use
      was related to decreased rates of mupirocin resistance at our hospital.

PMID- 16092751
TI  - Deoxyribozymes inhibit the expression of period1 gene in vitro.
AB  - To investigate the effect of two deoxyribozymes targeting period1 (per1) mRNA in
      vitro for exploring a novel gene therapy approach about circadian rhythm
      diseases, the specific deoxyribozymes targeting per1 were designed and
      synthesized chemically following MFold analysis according to its mRNA secondary
      structure. per1 RNA fragments were prepared by in vitro transcription of
      pcDNA3.1(+)-per1(164:256). The cleavage reactions containing deoxyribozymes and
      per1 RNA fragments were performed under certain conditions. With the transfection
      technique mediated by LipofectAMINE, pcDNA3-per1 and DRz164 or DRz256 were
      introduced into NIH3T3 cells. The effects of deoxyribozymes on per1 were studied
      by reverse transcript-polymerase chain reaction (RT-PCR) and flow cytometry
      (FCM). When deoxyribozymes and RNA transcripts were incubated under the adopted
      conditions at 37 degrees C for 2 h, about 63% of per1(164:256) RNA transcripts
      were cleaved by DRz164 and about 50.5% by DRz256. After cotransfecting pcDNA3
      per1 with DRz164 or DRz256, the expression of per1 mRNA was decreased, as
      indicated by RT-PCR semi-quantity analysis. FCM analysis showed that Per1 protein
      was inhibited. Both DRz164 and DRz256 targeting per1 have the specific cleavage
      activity toward per1 mRNA in vitro and can highly block the expression of per1
      gene in cellular milieu.

PMID- 16092753
TI  - Construction of a cucumber genetic linkage map with SRAP markers and location of
      the genes for lateral branch traits.
AB  - Using SRAP (sequence-related amplified polymorphism) markers a genetic linkage
      map of cucumber was constructed with a population consisting of 138 F2
      individuals derived from a cross of the two cucumber lines, S06 and S52. In the
      survey of parental polymorphisms with 182 primer combinations, 64 polymorphism
      revealing primer pairs were screened out, which generated totally 108 polymorphic
      bands with an average of 1.7 bands per primer pair and at most 6 bands from one
      primer pair. The constructed molecular linkage map included 92 loci, distributed
      in seven linkage groups and spanning 1164.2 cM in length with an average genetic
      distance of 12.6 cM between two neighboring loci. Based on this linkage map, the
      quantitative trait loci (QTL) for the lateral branch number (Ibn) and the lateral
      branch average length (Ibl) in cucumber were identified by QTLMapperl.6. A major
      QTL Ibn1 located between ME11 SA4B and ME5EM5 in LG2 could explain 10.63% of the
      total variation with its positively effecting allele from S06. A major QTL Ibl1
      located between DC1OD3 and DC1EM14 in LG2 could account for 10.38% of the total
      variation with its positively effecting allele from S06.

PMID- 16092752
TI  - Systemic induction of H2O2 in pea seedlings pretreated by wounding and exogenous
      jasmonic acid.
AB  - Pea seedlings (Pisum sativum L.) were used as materials to test the timings and
      compartments of hydrogen peroxide (H2O2) triggered by wounding and exogenous
      jasmonic acid (JA). The results showed that H2O2 could be systemically induced by
      wounding and exogenous JA. H2O2 increased within 1 h and reached the peak 3-5 h
      after wounding in either the wounded leaves or the unwounded leaves adjacent to
      the wounded ones and the inferior leaves far from the wounded ones. After this,
      H2O2 decreased and recovered to the control level 12 h after wounding. The
      activities of antioxidant enzymes, however, were rapidly increased by wounding.
      Diphenylene iodonium (DPI), an inhibitor of NADPH oxidase, could significantly
      inhibit H2O2 burst that was mediated by wounding and exogenous JA. Assay of H2O2
      subcellular location showed that H2O2 in response to wounding and exogenous JA
      was predominantly accumulated in plasma membrane, cell wall and apoplasmic space.
      Numerous JA (gold particles) was found via immunogold electron microscopy to be
      located in cell wall and phloem zones of mesophyll cell after wounding.

PMID- 16092754
TI  - Gene expression and molecular characterization of a thermostable trehalose
      phosphorylase from Thermoanaerobacter tengcongensis.
AB  - A gene encoding the trehalose phosphorylase (TreP), which reversibly catalyzes
      trehalose degradation and synthesis from alpha-glucose-1-phosphate (alpha-Glc-1
      P) and glucose, was cloned from Thermoanaerobacter tengcongensis and successfully
      expressed in Escherichia coli. The overexpressed TreP, with a molecular mass of
      approximately 90 kDa, was determined by SDS-PAGE. It catalyzes trehalose
      synthesis and degradation optimally at 70 degrees C (for 30 min), with the
      optimum pHs at 6.0 and 7.0, respectively. It is highly thermostable, with a 77%
      residual activity after incubation at 50 degrees C for 7 h. Under the optimum
      reaction conditions, 50 microg crude enzyme of the TreP is able to catalyze the
      synthesis of trehalose up to 11.6 mmol/L from 25 mmol/L alpha-Glc-1-P and 125
      mmol/L glucose within 30 min, while only 1.5 mmol/L out of 250 mmol/L trehalose
      is degraded within the same time period. Dot blotting revealed that the treP gene
      in T. tengcongensis was upregulated in response to salt stress but downregulated
      when trehalose was supplied. Both results indicate that the dominant function of
      the T. tengcongensis TreP is catalyzing trehalose synthesis but not degradation.
      Thus it might provide a novel route for industrial production of trehalose.

PMID- 16092755
TI  - Construction, detection and microarray analysis on the Shigella flexneri 2a sitC
      mutant.
AB  - In order to overcome the defects of difficult gene operations in low-copy suicide
      plasmid pCVD442, Gateway technology was applied in the construction process of
      recombinant plasmid for gene knockout in this study. With this improved knockout
      system, we inactivated sitC gene, which is associated with iron transport in
      Shigella flexneri 2a strain 301, to yield the mutant, MTS. The functional
      detection of the mutant was performed at the level of culture medium, cell and
      animal experiment, respectively. The gene expression profiles were compared with
      DNA microarray between the mutant and the wild type under iron-restricted
      conditions. The results showed that MTS grew obviously less well than the wild
      type strains in L broth containing 150 micromol/L iron chelator DIP (2,2'
      dipyridyl). Addition of iron or manganese to the cultures stimulated the growth
      of MTS to wild-type levels in rich culture medium. In either the experiment on
      the ability of intracellular multiplication and cell-to-cell spread in HeLa and
      U937 cell lines, or the experiment on keratoconjunctivitis in guinea pigs, MTS
      showed no obvious changes in virulence compared with the parental strain Sf301.
      When 65 micromol/L DIP was added to the cultured HeLa cells, the ability of
      intracellular multiplication of MTS reduced about 51.6% as compared with that of
      Sf301. The analysis of expression profiles under iron-limited condition showed
      that MTS was more sensitive for the change of iron deficiency than Sf301. There
      are 106 more up-regulated genes in MTS than in wild-type strains, which are
      involved in membrane transportation, amino acid metabolism and uncategorized
      function genes, while down-regulated genes are mainly involved in energy and
      carbohydrate metabolism. Under low iron conditions, the expression levels of
      known iron-transport associated genes generally increased. Additionally, the
      number of these genes and their increase amplitude in MTS are more than those in
      Sf301. Together, these results confirmed that Sit iron-transport system is
      important for the growth of Shigella.

PMID- 16092756
TI  - Key enzymes of the protocatechuate branch of the beta-ketoadipate pathway for
      aromatic degradation in Corynebacterium glutamicum.
AB  - Although the protocatechuate branch of the beta-ketoadipate pathway in Gram+
      bacteria has been well studied, this branch is less understood in Gram+ bacteria.
      In this study, Corynebacterium glutamicum was cultivated with protocatechuate, p
      cresol, vanillate and 4-hydroxybenzoate as sole carbon and energy sources for
      growth. Enzymatic assays indicated that growing cells on these aromatic compounds
      exhibited protocatechuate 3,4-dioxygenase activities. Data-mining of the genome
      of this bacterium revealed that the genetic locus ncg12314-ncg12315 encoded a
      putative protocatechuate 3,4-dioxygenase. The genes, ncg12314 and ncg12315, were
      amplified by PCR technique and were cloned into plasmid (pET21aP34D). Recombinant
      Escherichia coli strain harboring this plasmid actively expressed protocatechuate
      3,4-dioxygenase activity. Further, when this locus was disrupted in C.
      glutamicum, the ability to degrade and assimilate protocatechuate, p-cresol,
      vanillate or 4-hydroxybenzoate was lost and protocatechuate 3,4-dioxygenase
      activity was disappeared. The ability to grow with these aromatic compounds and
      protocatechuate 3,4-dioxygenase activity of C. glutamicum mutant could be
      restored by gene complementation. Thus, it is clear that the key enzyme for ring
      cleavage, protocatechuate 3,4-dioxygenase, was encoded by ncg12314 and ncg12315.
      The additional genes involved in the protocatechuate branch of the beta
      ketoadipate pathway were identified by mining the genome data publically
      available in the GenBank. The functional identification of genes and their unique
      organization in C. glutamicum provided new insight into the genetic diversity of
      aromatic compound degradation.

PMID- 16092757
TI  - The algae-lytic ability of bacterium DC10 and the influence of environmental
      factors on the ability.
AB  - A lysing-bacterium DC10, isolated from Dianchi Lake of Yunnan Province, was
      characterized to be Pseudomonas sp. It was able to lyse some algae well, such as
      Microcystis viridis, Selenastrum capricornutum, and so on. In this study, it was
      shown that the bacterium lysed the algae by releasing a substance; the best lytic
      effects were achieved at low temperatures and in the dark. Different
      concentrations of CaCl2 and NaNO3 influenced the lytic effects; the ability to
      lyse algae decreased in the following order: pH 4 > pH 9 > pH 7 > pH 5.5. It was
      significant to develop a special technology with this kind of bacterium for
      controlling the bloom-forming planktonic microalgae.

PMID- 16092758
TI  - Interaction of restin with transcription factors.
AB  - Restin, a member of melanoma-associated antigen superfamily gene, was first
      cloned from differentiated leukemia cell induced by all trans-retinoic acid, and
      was able to inhibit cell proliferation, but the molecular mechanism was not
      clear. Since Restin was localized in cell nucleus, and its homolog member, Necdin
      (neuronal growth suppressor factor), could interact with transcription factors
      p53 and E2F1, we proposed that Restin might also function as Necdin through
      interacting with some transcription factors. In this study, transcription factors
      p53, AP1, ATFs and E2Fs were cloned and used in the mammalian two-hybrid system
      to identify their interaction with Restin. The results showed that only ATF3 had
      a strong interaction with Restin. It is interesting to know that ATF3 was an
      important transcription factor for G1 cell cycle initiation in physiological
      stress response. It was possible that the inhibition of cell proliferation by
      Restin might be related with the inhibition of ATF3 activity.

PMID- 16092759
TI  - Multi-locus association study of schizophrenia susceptibility genes with a
      posterior probability method.
AB  - Schizophrenia is a serious neuropsychiatric illness affecting about 1% of the
      world's population. It is considered a complex inheritance disorder. A number of
      genes are involved in combination in the etiology of the disorder. Evidence
      implicates the altered dopaminergic transmission in schizophrenia. In the present
      study, in order to identify susceptibility genes for schizophrenia in
      dopaminergic metabolism, we analyzed 59 single nucleotide polymorphisms (SNPs) in
      24 genes of the dopaminergic pathway among 82 unrelated patients with
      schizophrenia and 108 matched normal controls. Considering that traditional
      single-locus association studies ignore the multigenic nature of complex diseases
      and do not take into account possible interactions between susceptibility genes,
      we proposed a multi-locus analysis method, using the posterior probability of
      morbidity as a measure of absolute disease risk for a multi-locus genotype
      combination, and developed an algorithm based on perturbation and average to
      detect the susceptibility multi-locus genotype combinations, as well as to
      repress noise and avoid false positive results at our best. A three-locus SNP
      genotype combination involved in the interactions of COMT and ALDH3B1 genes was
      detected to be significantly susceptible to schizophrenia.

PMID- 16092760
TI  - Human pescadillo induces large-scale chromatin unfolding.
AB  - The human pescadillo gene encodes a protein with a BRCT domain. Pescadillo plays
      an important role in DNA synthesis, cell proliferation and transformation. Since
      BRCT domains have been shown to induce chromatin large-scale unfolding, we tested
      the role of Pescadillo in regulation of large-scale chromatin unfolding. To this
      end, we isolated the coding region of Pescadillo from human mammary MCF10A cells.
      Compared with the reported sequence, the isolated Pescadillo contains in-frame
      deletion from amino acid 580 to 582. Targeting the Pescadillo to an amplified,
      lac operator-containing chromosome region in the mammalian genome results in
      large-scale chromatin decondensation. This unfolding activity maps to the BRCT
      domain of Pescadillo. These data provide a new clue to understanding the vital
      role of Pescadillo.

PMID- 16092761
TI  - Hepatitis B virus X protein modulates the apoptosis of hepatoma cell line induced
      by TRAIL.
AB  - The purpose of this study is to observe the effects of HBx on the apoptosis of
      hepatoma cells induced by TNF-related apoptosis-inducing ligand (TRAIL) and to
      study preliminary molecular mechanisms for its effects. In order to set up a
      model in vitro, BEL7402-HBx cell line, stably expressing HBx mRNA, was
      established by stable transfection of pcDNA-HBx, which contains HBx gene, into
      hepatoma cell line BEL7402. Control cell line BEL7402-cDNA3, stably transfected
      with pcDNA3, was set up simultaneously as a control. Trypan blue exclusion test,
      caspase 3 activity detection and TUNEL assay were performed to detect the
      apoptosis of BEL7402, BEL7402-cDNA3, BEL7402-HBx induced by TRAIL. The expression
      of TRAIL receptors in three groups was analyzed by Flow cytometry. In addition,
      phosphorothioated antisense oligonucleotide against the translation initial
      region of HBx gene (PS-asODNs/HBx) was used to block the expression of HBx in
      HepG2.2.15 cells and to further confirm the effects of HBx on TRAIL-induced
      apoptosis. Trypan blue exclusion test indicated that TRAIL had a dose-dependent
      cytotoxicity on BEL7402, BEL7402-cDNA3 and BEL7402-HBx cells. Under treatment of
      the same concentration of TRAIL, BEL7402-HBx had a higher apoptosis rate and a
      higher level of Caspase 3 activation than BEL7402 and BEL7402-cDNA3. TUENL assay
      showed that the apoptosis rate of BEL7402-HBx induced by 10 microg/L TRAIL was
      41.4% +/- 7.2%, significantly higher than that of BEL7402 and BEL7402-cDNA3
      cells. Blockade of HBx expression in Hep G2.2.15 cells partly inhibited the
      apoptosis induced by TRAIL. The introduction or blockade of HBx did not change
      the expression pattern of TRAIL receptors. The present study firstly confirms the
      effects of HBx on TRAIL- induced apoptosis from two different points and it is
      not related with the expression level of TRAIL receptors. This would be useful to
      further clarify the roles of imbalanced apoptosis in pathogenesis of Hepatitis B
      and related hepatocellular carcinoma.

PMID- 16092762
TI  - The effects of proteasome inhibitor lactacystin on mouse oocyte meiosis and first
      cleavage.
AB  - In order to study the effects of ubiquitin-proteasome pathway (UPP) on mouse
      oocyte meiosis and cleavage, oocytes undergoing maturation and parthenogenetic
      activation and 1-cell embryos were treated with lactacystin, a specific inhibitor
      of proteasome. The results indicated that the rate of GVBD was not influenced by
      the treatment, but polar body extrusion, parthenogenesis and first cleavage were
      inhibited. Immunofluorescent staining using anti beta-tubulin antibody indicated
      that the continuous treatment of lactacystin from GV stage disorganized
      microtubules and spindle assembly. When metaphase stage oocytes were treated with
      the drug, the already formed spindle structure was not affected, but the oocytes
      were arrested at metaphases. The 1-cell embryos were arrested at interphase or
      metaphase of first mitosis when they were incubated in the drug. Proteasome
      regulatory subunit PA700 was located in the spindle region, as indicated by
      immunofluorescence. These results suggest that UPP has effects on the process of
      oocyte meiosis and early cleavage in many aspects, including normal organization
      of spindle at prophase and segregation of chromosomes at anaphase for normal
      meiosis.

PMID- 16092763
TI  - Neural precursors derived from human embryonic stem cells.
AB  - Human embryonic stem (hES) cells provide a promising supply of specific cell
      types for transplantation therapy. We presented here the method to induce
      differentiation of purified neural precursors from hES cells. hES cells (Line PKU
      1 and Line PKU-2) were cultured in suspension in bacteriological Petri dishes,
      which differentiated into cystic embryoid bodies (EBs). The EBs were then
      cultured in N2 medium containing bFGF in poly-L-lysine-coated tissue culture
      dishes for two weeks. The central, small cells with 2-3 short processes of the
      spreading outgrowth were isolated mechanically and replated. The resulting
      neurospheres were cultured in suspension for 10 days, then dissociated into
      single cell suspension with a Pasteur pipette and plated. Cells grew vigorously
      in an attached way and were passed every 4-5 days. Almost all the cells were
      proved nestin positive by immunostaining. Following withdrawal of bFGF, they
      differentiated into neurons expressing beta-tubulin isotype(III), GABA, serotonin
      and synaptophysin. Through induction of PDGF-AA, they differentiated into
      astrocytes expressing GFAP and oligodendrocytes expressing O4. The results showed
      that hES cells can differentiate into typical neural precursors expressing the
      specific marker nestin and capable of generating all three cell types of the
      central nervous system (CNS) in vitro.

PMID- 16092764
TI  - Applications of the double-barreled data in whole-genome shotgun sequence
      assembly and analysis.
AB  - Double-barreled (DB) data have been widely used for the assembly of large
      genomes. Based on the experience of building the whole-genome working draft of
      Oryza sativa L. ssp. Indica, we present here the prevailing and improved uses of
      DB data in the assembly procedure and report on novel applications during the
      following data-mining processes such as acquiring precise insert fragment
      information of each clone across the genome, and a new kind of low-cost whole
      genome microarray. With the increasing number of organisms being sequenced, we
      believe that DB data will play an important role both in other assembly
      procedures and in future genomic studies.

PMID- 16092765
TI  - The impact of federal tax exemption standards on health care policy and delivery.

PMID- 16092766
TI  - The failure of community benefit.
AB  - Though proponents of tax exemption for health care providers continue to extol
      the virtues of the community-benefit test, Part II of this article illustrates
      that the train pretty much has already left the station on this front. Both the
      federal government and the states increasingly look to uncompensated care as the
      touchstone of exemption for health care providers. To a great extent, this
      transition back to a "relief of the poor" standard for exemption is the result of
      the inherent lack of precision in community benefit standards, along with the
      general trend of empirical evidence that nonprofit health care providers behave
      similarly to their for-profit counterparts. Faced with this situation, federal
      and state policymakers naturally have focused on charity care as the one
      quantifiable behavioral difference to justify exemption. Nevertheless, some
      empirical evidence suggests that nonprofits may engage in socially desirable
      behavior other than simply free care for the poor, and the arguments that a mixed
      ownership system provides the best overall health care model cannot be dismissed
      out of hand. Thus, despite my past criticisms of the community benefit
      formulation, I have come to the view that we should seriously consider the
      options available beyond complete repeal of the community benefit test or a
      return to a strict charity-care exemption standard. I continue to believe that we
      should demand a fairly high level of "accountability" from exemption, however,
      and that exemption should have some direct causal connection to whatever socially
      desirable behavior we are seeking. While one option along these lines is to adopt
      Nina Crimm's approach of rewarding specific behaviors through a deduction or
      credit system, using "enhancing access" as a test of exemption may provide the
      best combination of flexibility and verifiable behavioral differences to support
      continued exemption for health care providers.

PMID- 16092767
TI  - Executive compensation in nonprofit health care organizations: who's in charge?

PMID- 16092768
TI  - Health care joint ventures between tax-exempt organizations and for-profit
      entities.
AB  - Health care exempt organizations have many options regarding their structure and
      affiliations with for-profit entities. As long as any joint ventures are
      carefully structured and the nonprofit retains control over the exempt health
      care activities, the Internal Revenue Service should not question the structure.
      However, as outlined above, if the for-profit entity effectively gains control
      over the activities of the venture, the structure is not likely to be upheld by
      the IRS or the courts, and either the exempt status of the nonprofit will be
      denied or revoked, or health care income will be subject to the unrelated
      business income tax. In summary, the health care industry has been severely
      impacted by many economic forces, including uncertainty in the area of joint
      ventures between nonprofits and for-profit health care systems. The uncertainty
      as to whether the joint venture would negatively impact the nonprofit's tax
      exempt status undoubtedly caused many nonprofits to form for-profit subsidiaries
      and otherwise expanded operations in a for-profit marketplace. Fortunately, with
      the guidance that is currently available in the form of Revenue Ruling 98-15,
      Redlands, St. David's, and now Revenue Ruling 2004-51, health care institutions
      can move forward with properly structured joint ventures with greater confidence
      that the joint venture will not endanger the tax-exempt status of the nonprofit.

PMID- 16092769
TI  - Do fiduciary duties contained in federal tax laws effectively promote national
      health care policies and practices?

PMID- 16092770
TI  - Medical education and malpractice: what's the connection?

PMID- 16092771
TI  - Why so glum? Toward a fair balance of competitive interests in direct-to-consumer
      advertising and the well-being of the mentally ill consumers it targets.

PMID- 16092772
TI  - Prompt pay statutes should be interpreted to grant providers a private right of
      action to seek enforcement against payors.

PMID- 16092773
TI  - Is antidepressant drug discontinuation warranted prior to polygraph
      administration?

PMID- 16092774
TI  - Open access: a hot topic in the publishing world.

PMID- 16092775
TI  - Knowing is not enough: we must do.

PMID- 16092776
TI  - Directions in palliative care nursing research: impeccable care, timing, and
      complexity.

PMID- 16092777
TI  - Self-determination: analysis of the concept and implications for research in
      palliative care.
AB  - This paper analyzes the evolution and the definition, current use, and
      application of the concept of self-determination in palliative care research and
      practice. Undertaken as a foundation for the development of a palliative care
      research program, the analysis considers selected historical, bioethical, legal,
      clinical, and relevant medical and nursing health-care literature on adults with
      chronic and terminal illness. Based on a synthesis of the literature, a
      conceptual definition is proposed and ways of integrating the concept of self
      determination into palliative care intervention research are identified.

PMID- 16092778
TI  - Methodological issues in researching palliative care nursing practice.
AB  - The purpose of this integrative review was to describe the research conducted by
      nurses since the mid-1990s on nursing practice in the context of palliative/end
      of-life care, identify promising methodological developments as well as
      methodological challenges, and propose strategies to support the development of
      this field of nursing research. A search of databases resulted in 121 research
      reports published between 1995 and 2003. Studies were included if the lead author
      was a nurse and the focus was nursing practice or nurses' attitudes about
      providing palliative or end-of-life care. Relatively few studies included
      patients, there were limitations in the data-collection methods used, and there
      was a lack of studies evaluating palliative care nursing. An emphasis on the
      interdisciplinary nature of palliative care may be hindering nurses from
      examining the effectiveness of nursing interventions. Increased attention should
      be given to examining the efficiency and effectiveness of nursing interventions
      to ensure the best outcomes for patients and their families.

PMID- 16092779
TI  - Transforming hope: how elderly palliative patients live with hope.
AB  - Hope is important to palliative patients; however, the process by which these
      patients live with hope is unknown. The purpose of this study was to describe,
      using a grounded theory approach, the processes by which palliative patients live
      with hope. Sixteen interviews were conducted with 10 home-care palliative
      patients (mean age 75 years) in their homes using open-ended questions. The
      participants defined their hope as expectations such as not suffering more and
      having a peaceful death. They described their main concern as wanting to "live
      with hope" and they achieved this through the basic social process of
      transforming hope. Transforming hope involved acknowledging "life the way it is,"
      searching for meaning, and positive reappraisal. The results of this study
      provide a foundation for future research and the development of interventions to
      engender hope in older palliative patients.

PMID- 16092780
TI  - Palliative care research in practice.

PMID- 16092781
TI  - The promise of quality care at the end of life takes a leap forward.

PMID- 16092782
TI  - The Manitoba Palliative Care Research Unit: collaboration in action.

PMID- 16092783
TI  - Knowledge translation in palliative care: can theory help?

PMID- 16092784
TI  - Profiling Canadian nurses' preferred knowledge sources for clinical practice.
AB  - Several researchers have examined nurses' knowledge sources within the context of
      research utilization, but conclusions are equivocal. Common problems include a
      lack of replication, conflicting results, poor generalizability of results, and
      unclear implications for practice. The objectives of this study were to: (a)
      describe sources of knowledge and their frequency of use among staff nurses
      across 7 surgical units, (b) compare knowledge-source patterns across the units,
      (c) determine whether knowledge-source preferences correlate to research
      utilization scores, and (d) profile staff nurses' knowledge-source patterns over
      time. A total of 230 nurses in 5 adult and 2 pediatric surgical units from 4
      hospitals in the Canadian provinces of Alberta and Ontario completed a self
      administered survey. The results were compared to the findings of previous
      studies. Nurses' knowledge-source preferences were consistent across the 7 units
      despite differences in education and in research utilization scores. Across all
      units, nurses preferred to use knowledge gained through personal experience and
      interactions with co-workers and with individual patients rather than journal
      articles or textbooks. These findings are consistent with the longitudinal
      comparison in the 2 earlier studies. In contrast to the knowledge privileged by
      nurse clinicians, researchers tend to place greater value on research-based
      knowledge than on experience-based knowledge. To increase research utilization in
      the practice setting, researchers and others need first to understand the reasons
      behind clinicians' valuing of experiential and social knowledge sources and then
      to consider research dissemination and implementation strategies that are more
      closely aligned with clinician preferences.

PMID- 16092785
TI  - A qualitative investigation of seniors' and caregivers' views on pain assessment
      and management.
AB  - The literature suggests that pain in the elderly, especially among seniors with
      dementia, is under-assessed and under-treated. This qualitative study solicited
      the perspectives of seniors, front-line nursing staff, nursing-home
      administrators, and informal caregivers of seniors with dementia on the current
      status of pain assessment and management. The views of these participants
      complement the research findings reported in the literature. While some of their
      explanations and potential solutions concerning under-treatment of pain in
      seniors echo views that have been presented in the literature, the participants
      also pointed to factors and avenues that have been given less formal
      consideration (e.g., systemic barriers to effective assessment and treatment of
      pain). They also highlighted the need for pain-control strategies beyond
      medication. The implications of these findings are discussed.

PMID- 16092786
TI  - Expanding the dialogue on dementia: (Re)positioning diagnosis and narrative.
AB  - The biomedical model that guides the processes of assessment and diagnosis of
      dementia is based on assumptions and approaches which, while critical to
      medicine, may render them less consequential for nursing. Although gerontological
      nurses' research concerning dementia frequently uses the diagnosis as an
      inclusion criterion for projects, and screening tools are often employed to
      evaluate the impact of interventions, we may wish to consider expanding our views
      of assessment and evaluation to include the person's narrative. The purpose of
      this paper is to argue for this expanded dialogue and to suggest that nurses
      reposition the medical diagnosis behind the narrative of the individual patient.
      To that end, this paper explores and critiques the limitations of the diagnostic
      process and questions its relevance to nursing. The alternative considerations
      that are discussed include constructionist and interpretivist approaches, the
      exploration of assumptions, and a relational approach to supporting personhood.

PMID- 16092787
TI  - Anatomical theatres and the teaching of anatomy in early modern Spain.

PMID- 16092788
TI  - The British market for medicine in the late nineteenth century: the innovative
      impact of S M Burroughs & Co.

PMID- 16092789
TI  - Alligation alternate and the composition of medicines: arithmetic and medicine in
      early modern England.

PMID- 16092790
TI  - Midwives and their role in the reduction of direct obstetric deaths during the
      late nineteenth century: the Sundsvall region of Sweden (1860-1890).

PMID- 16092791
TI  - Doctoring beauty: the medical control of women's toilettes in France, 1750-1820.

PMID- 16092792
TI  - Introduction: welcome to the next generation of acne research.

PMID- 16092793
TI  - Insights in the pathogenic potential of Propionibacterium acnes from its complete
      genome.
AB  - One of the long-lasting open questions in understanding acne is the role of the
      skin bacterium Propionibacterium acnes. Opinions within the scientific community
      diverge regarding the importance of this Gram-positive bacterium not only in acne
      but also in other P. acnes-associated diseases. The recently decoded genome gives
      us some clues with respect to its pathogenic potential and its strategies to
      survive in the harsh environment of human skin. This review focuses on the major
      findings of the genome sequence. Special attention has been drawn to the cell
      surface composition of P. acnes, its antigenic potential, and to enzymes that are
      potentially involved in degrading skin-derived substances.

PMID- 16092794
TI  - The role of toll-like receptors in the pathophysiology of acne.
AB  - Acne vulgaris is a common cutaneous disorder of the pilosebaceous follicle,
      affecting more than 45 million people in the United States alone. The
      pathogenesis of acne is multifactorial, involving abnormal hyperkeratinization,
      increased sebum production, hormones, cutaneous microbes, and immunological
      mechanisms. Many of the immunological processes that contribute to the formation
      of acne lesions take place at the very site of disease, the skin. Skin is an
      important component of the innate immune system, providing both physical barriers
      and rapid cellular responses by keratinocytes, Langerhans cells, and other
      infiltrating inflammatory cells. In this review, we discuss the ability of the
      innate immune system to use Toll-like receptors (TLRs) to recognize microbial
      patterns and initiate immune responses in cutaneous disorders. Because TLRs are
      vital players in infectious and inflammatory diseases, they are potential
      therapeutic targets. Indeed, the ability of TLRs to combat disease already has
      been harnessed through the development of drugs that act as TLR agonists. A
      better understanding of TLRs will allow for the development of new therapeutic
      options for cutaneous inflammatory diseases such as acne.

PMID- 16092795
TI  - The role of inflammation in the pathogenesis of acne and acne scarring.
AB  - Evidence now supports a pivotal role for cellular inflammatory events at all
      stages of acne lesion development, from preclinical initiation to clinical
      presentation of active lesions through to resolution. The emphasis has moved from
      acne as a primarily hyperproliferative disorder of the sebaceous follicle to that
      of an inflammatory skin disorder. However, although the sequence of events
      leading to lesion formation has become clearer, the triggers for initiation
      remain speculative. The development of noninvasive techniques to detect
      preclinical "acne-prone" follicles is essential before triggers for initiation
      can be defined. Finally, the differences highlighted in the inflammatory profiles
      of inflamed lesions from patients who scar, as compared with other nonscarring
      acne patients reinforces the view that acne is a disorder, which embraces a
      number of pathologies.

PMID- 16092796
TI  - Implications for the role of diet in acne.
AB  - Within the dermatology community, a general consensus has emerged that diet is
      unrelated to the etiology of acne. Except for 2 poorly designed studies, now more
      than 30 years old, there are few objective data to support this notion. In
      contrast, a large body of evidence now exists showing how diet may directly or
      indirectly influence the following 5 proximate causes of acne: (1) increased
      proliferation of basal keratinocytes within the pilosebaceous duct, (2)
      incomplete separation of ductal corneocytes from one another via impairment of
      apoptosis and subsequent obstruction of the pilosebaceous duct, (3) androgen
      mediated increases in sebum production, (4) colonization of the comedo by
      Propionibacterium acnes, and (5) inflammation both within and adjacent to the
      comedo. This article will provide a review of the currently available literature
      on the association between diet and acne vulgaris as well as a discussion of the
      physiologic principles that may underlie this association.

PMID- 16092797
TI  - Depression and suicidal behavior in acne patients treated with isotretinoin: a
      systematic review.
AB  - Isotretinoin (13-cis retinoic acid) is an effective treatment for severe cystic
      or recalcitrant acne vulgaris; however, concerns have been raised regarding its
      potential association with depression and suicidal behavior. We sought to explore
      the proposed relationship between isotretinoin use and the risk of depression and
      attempted and completed suicide in patients with acne vulgaris by performing a
      systematic literature search for studies reporting primary data on depression and
      suicidal behavior in patients treated with isotretinoin for acne vulgaris. Nine
      studies met the qualifying criteria for our analysis. Rates of depression among
      isotretinoin users ranged from 1% to 11% across studies, with similar rates in
      oral antibiotic control groups. Overall, studies comparing depression before and
      after treatment did not show a statistically significant increase in depression
      diagnoses or depressive symptoms. Some, in fact, demonstrated a trend toward
      fewer or less severe depressive symptoms after isotretinoin therapy. This
      decrease was particularly evident in patients with pretreatment scores in the
      moderate or clinical depression range. No correlation between isotretinoin use
      and suicidal behavior was reported, although only one retrospective study
      presented data on this topic. Although the current literature does not support a
      causative association between isotretinoin use and depression, there are
      important limitations to many of the studies. The available data on suicidal
      behavior during isotretinoin treatment are insufficient to establish a meaningful
      causative association.

PMID- 16092798
TI  - Hormonal therapy for acne using oral contraceptive pills.
AB  - The etiology of acne vulgaris is multifactorial and complex. The four key factors
      involved in the development of acne include follicular plugging, inflammation,
      the presence and activity of Propionibacterium acnes, and sebum. Androgen
      hormones stimulate the sebaceous gland and promote sebum excretion. Therefore,
      therapies that have an overall antiandrogen effect, like combination oral
      contraceptive pills, may be useful in the management of acne vulgaris. Numerous
      combination oral contraceptive pills have been evaluated in the treatment of acne
      vulgaris and have been found to be effective. With a thorough understanding of
      their proper use and potential associated risks, these hormonal treatments may be
      prescribed safely and effectively to women with acne.

PMID- 16092799
TI  - Lasers and light therapy for acne vulgaris.
AB  - Acne vulgaris remains an emotionally and debilitating dermatologic disease, and
      is conventionally treated with a variety of oral and topical therapies with a
      number of significant side effects. An evolving understanding of laser-tissue
      interactions involving Propionibacterium acnes-produced porphyrins, and the
      development of infrared nonablative lasers to target sebaceous glands, has lead
      to the development of an escalating number of laser, light and radiofrequency
      devices for acne. Used as monotherapy or in combination, these devices are
      showing promise as a method to clear acne in a convenient, non-invasive manner,
      though there remains a clear need for long-term data and randomized, blinded
      studies.

PMID- 16092800
TI  - Complementary and integrative therapies. Introduction.

PMID- 16092801
TI  - MindBodySpirit Medicine.
AB  - OBJECTIVES: To present an overview of MindBodySpirit medicine including
      discussions of the efficacy of select self-care approaches. DATA SOURCES:
      Research and clinical articles on select complementary interventions. The model
      developed by the Center for Mind Body Medicine. CONCLUSION: Good information,
      self-care skills, and a supportive environment can assist an individual to
      achieve a higher level of physical, emotional, and spiritual wellness while
      navigating the cancer experience. IMPLICATIONS FOR NURSING PRACTICE: Increasing
      numbers of patients with cancer are becoming active in their health care and are
      choosing complementary approaches. There is an increasing body of literature
      supporting these interventions in improving quality of life. Nurses can acquire
      information to help patients navigate the expanding arena of complementary
      practices. "What Else Can I Do?" "What Else Can I Do?"

PMID- 16092802
TI  - Spiritual complementary therapies in cancer care.
AB  - OBJECTIVES: To review literature documenting the frequency of use and efficacy of
      spiritual complementary therapies. Implications for clinical practice and
      research that reflect this literature are offered. DATA SOURCES: Data based
      research on complementary therapy usage and clinical articles about selected
      mind/body therapies. CONCLUSION: Spiritual complementary therapies are among the
      most frequently used. Prayer, spiritual healing, and meditation are the most
      frequently used spiritual therapies. Equivocal evidence supports their efficacy.
      IMPLICATIONS FOR NURSING PRACTICE: Although spiritual practices may not be
      considered a "therapy," clinicians should assess and support these practices.
      Clinicians should only pray with patients when observing ethical guidelines.

PMID- 16092803
TI  - Reintroduction to nutrition and cancer treatment.
AB  - OBJECTIVES: To review what constitutes optimal nutrition for the cancer patient.
      DATA SOURCES: Conventional nutrition, botanical and biomedical journals and
      texts, electronic media, databases, and abstracts. CONCLUSION: Optimal nutrition
      is neither a complementary nor alternative treatment, but is the fundamental
      groundwork for the creation of the most favorable cancer treatment outcomes as
      presented in numerous study findings and journal articles. The two main topics of
      this article are (1) general food choices and decisions that can affect treatment
      outcomes; and (2) a brief look at the specific scientific application of
      individual nutrients to affect a positive impact on treatment, protection of
      healthy cells and tissues, side-effect mitigation, and quality of life for cancer
      patients. IMPLICATIONS FOR NURSING PRACTICE: It is critical for health care
      providers to both acknowledge and apply the principles of nutrition for cancer
      patients both in general and as part of a therapeutic regimen. It is important
      for nursing staff to understand that nutritional elements can promote or detract
      from cancer treatment and recovery.

PMID- 16092804
TI  - Alternative nutrition therapies in cancer patients.
AB  - OBJECTIVES: To review diet guidelines on selected alternative nutrition
      therapies, and the origins, limitations, and implication of these
      recommendations. DATA SOURCES: Clinical research articles on alternative
      nutrition therapy. CONCLUSION: Alternative nutrition therapy will continue to
      receive increasing scrutiny as research in science and technology develops.
      Individual needs vary widely; there is not one perfect diet for everyone.
      However, nutrition/diet plays a major role in cancer care and patients need to be
      educated about safe alternative nutrition therapy. IMPLICATIONS FOR NURSING
      PRACTICE: Whatever decision patients make regarding alternative nutrition
      therapies, support should be provided so that communication is increased between
      the patient and the health care team.

PMID- 16092805
TI  - Herbal medicine and cancer: an introductory overview.
AB  - OBJECTIVES: To present Western herbal medicine from the perspective of a "food"
      model of herbs in contrast to the pharmaceutical "drug" model derived from
      mainstream medicine. Historical, political, and regulatory aspects of herbal
      medicine in the United States; core principles of herbal medicine in terms of the
      natural link between food and medicine; dietary chemopreventive plant compounds
      in the form of herbal medicines; and herb-drug interactions are briefly
      discussed, with an emphasis on beneficial interactions with conventional
      chemotherapy. DATA SOURCES: Literature on dietary chemopreventive compounds;
      phytotherapeutic training and clinical practice. CONCLUSION: Botanical medicine,
      based on dietary chemopreventive compounds plays an important role in integrative
      cancer treatment. IMPLICATIONS FOR NURSING PRACTICE: Knowledge of the differences
      between herbal and conventional medicine in terms of a food, medicine, and poison
      model will help nurses facilitate patient decision-making choices in integrative
      cancer treatment.

PMID- 16092806
TI  - Alternatives in cancer pain treatment: the application of chiropractic care.
AB  - OBJECTIVES: To review written resources disclosing reliable facts and knowledge
      in chiropractic services in cancer pain management. DATA SOURCES: Conventional
      and biomedical and complementary and alternative medicine journals, electronic
      media, full text databases, electronic resources, books in print, and
      newsletters. CONCLUSION: The judicial use of chiropractic services in cancer
      patients appears to offer many economical and effective strategies for reducing
      the pain and suffering of cancer patients, as well as providing the potential to
      improve patient health overall. IMPLICATIONS FOR NURSING PRACTICE: Clinicians
      should assess and support the use of chiropractic services in cancer patients.
      Chiropractic is one of the leading alternatives to standard medical treatment in
      cancer pain management.

PMID- 16092807
TI  - Acupuncture for side effects of chemoradiation therapy in cancer patients.
AB  - OBJECTIVE: To review strategies and recommendations to improve utilization of
      acupuncture treatment for side effects of chemoradiation therapy in cancer
      centers. DATA SOURCES: Research studies and articles, government reports, and
      author experience. CONCLUSION: Recent evidence in clinical research indicates
      that acupuncture is beneficial for chemotherapy-induced nausea, vomiting, and
      cancer pain. Other preliminary data also suggests acupuncture might be effective
      for chemotherapy-induced leukopenia, postchemotherapy fatigue, radiation therapy
      induced xerostomia, insomnia, and anxiety. However, the utilization rate of
      acupuncture remains low despite the wide use of other complementary and
      alternative medical therapies among cancer patients. This low usage of
      acupuncture in cancer patients indicates a health care quality issue.
      IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses need to increase their
      awareness of the available evidence in the use of acupuncture in the supportive
      care of cancer patients.

PMID- 16092808
TI  - Biofield considerations in cancer treatment.
AB  - OBJECTIVES: To explore the biofield aspect of cancer care; to identify the
      benefits of energetic approaches in cancer care; and to examine one approach
      through a case study. DATA SOURCES: Current research and national reports on
      biofield approaches in complementary therapies. CONCLUSION: Caring for the
      biofield is important in assisting the patient with cancer to enhance vitality,
      reduce pain, fatigue, and other side effects as a result of cancer treatments.
      IMPLICATIONS FOR NURSING PRACTICE: Cancer care must be holistic to provide
      maximal healing opportunities for patients. Consideration of the biofield is an
      important aspect of this care.

PMID- 16092809
TI  - Communicating facts and knowledge in cancer complementary and alternative
      medicine.
AB  - OBJECTIVES: To review written resources disclosing reliable facts and knowledge
      in cancer complementary and alternative medicine (CAM). DATA SOURCES:
      Conventional and biomedical and complementary and alternative medicine journals,
      electronic media, full text databases, electronic resources, and newsletters.
      CONCLUSION: Sources of CAM information are numerous. The inherent quality of this
      information fluctuates. High-quality sources of cancer CAM information are
      available and accessible for health care providers. IMPLICATIONS FOR NURSING
      PRACTICE: As the use of CAM therapies becomes more commonplace in consumer health
      care, it is critical that health care providers are cognizant of available
      sources of high-quality CAM facts and knowledge and possess the ability to
      discuss this information with colleagues and consumers in the scientific and lay
      communities.

PMID- 16092810
TI  - Future direction of complementary and alternative medicine (CAM) education and
      research.
AB  - OBJECTIVES: To identify key educational and scientific tasks for the
      incorporation of complementary and alternative medical therapies (CAM) into
      conventional health care. DATA SOURCES: Journal articles, government and special
      health report, book chapters, and curriculum guidebooks. CONCLUSION: Nursing
      education programs are rapidly adding curricula on the practice and research of
      CAM therapies. The next priority is to facilitate consistency and quality of
      educational programs by developing standards of practice and a core curriculum.
      Educational standards agreed upon by the nursing profession and set at the
      undergraduate, graduate, and professional levels will help guide the safe and
      effective integration of CAM into conventional health care. IMPLICATIONS FOR
      NURSING PRACTICE: Setting educational standards and developing consistent
      curricula for CAM will help students emerge from academic programs prepared for
      safe and effective practice and with skills to evaluate the effectiveness and
      participate in the research of CAM therapies.

PMID- 16092812
TI  - Internal distraction plating of distal radius fractures.
AB  - Internal distraction plating can be used for the treatment of highly comminuted
      distal radius fractures especially in elderly patients. The technique involves
      the use of 3.5, 2.7, or 2.5 dynamic compression plates. The instrumentation is
      applied in distraction dorsally from the radial diaphysis, bypassing the
      comminuted segment, and fixed distally to the long metacarpal. The advantages of
      this technique are: a) it can be used as an alternative for managing difficult
      fractures in the elderly population; b) it is indicated in patients with
      osteoporotic bone; c) complications associated with external pins are avoided;
      and d) the stability of the plate allows patients to use the extremity for
      transfer and activities of daily living. On the other hand, possible
      disadvantages to be considered are: a) the need of a second operation to remove
      the plate; and b) the prolonged duration of immobilization. Elderly patients with
      osteoporotic bone who undergo treatment of comminuted distal radius fractures may
      result in poor outcomes with high rates of complications if external fixation or
      standard internal fixation is used. The current approach represents an
      alternative that provides union of the fracture with excellent alignment,
      functional range of motion, and minimal functional disability.

PMID- 16092813
TI  - Treatment of unstable extra-articular distal radius fractures by modified
      intrafocal Kapandji method.
AB  - The authors prospectively assess the results of surgically treated, unstable
      extra-articular distal radius fractures from 29 patients with good bone quality.
      Mean age was 49 years, ranging from 22 to 69 years; the female gender was the
      most frequently affected (58.6% of the cases). Surgical fixation was indicated
      for fractures presenting an angulation above 20 degrees , marked dorsal
      comminution, and radius shortening in excess of 10 mm on initial x-rays
      (anteroposterior and lateral views). The Kapandji technique, with intrafocal,
      nonthreaded Kirschner wires, was employed. Clinical data assessed anatomic
      aspects according to Scheck, functional aspect after Gartland and Werley,
      strength by Scheck's methods, and esthetic by Frykman's criteria. Functional
      assessment, according to Gartland and Werley, revealed 72.1% of excellent and
      good results at 3 months; 89.7% at 6 months; and 96.6% at 12 months. Immediate
      postoperative reduction was not maintained at the final follow-up at 12 months;
      however, that loss was not severe, and the anatomic outcome was good and
      excellent in 96.6% of the cases. Six patients presented complications. Four
      patients presented reflex sympathetic dystrophy; 1 patient had a superficial
      Kirschner wire infection, and another patient had radial nerve superficial branch
      paresthesia. The employed technique showed to be effective in the treatment of
      unstable, extra-articular fractures of the distal radius. It is easy to learn and
      to perform. The device employed has a low cost and is widely available in
      operation rooms.

PMID- 16092814
TI  - Condylar stabilizing technique for intra-articular fracture of distal radius.
AB  - I previously reported a new reduction and fixation technique for extra-articular
      distal radius fracture associated with osteoporosis. I developed the technique
      and applied it to intra-articular fracturea. I present here the technique and
      verify its reliability, comparing the functional results of intra-articular
      fracture cases to those of extra-articular cases.

PMID- 16092815
TI  - Temporary fixation with the Agee-Wristjack during correctional osteotomies for
      malunions and nonunions of the distal radius.
AB  - Upper extremity surgeons are often responsible for managing complex malunions and
      nonunions of distal radius fractures. Studies have demonstrated that corrective
      osteotomies of the malunited distal radius with placement of sculpted bone grafts
      produce the best functional and cosmetic results in patients. We describe a
      technique for providing provisional stabilization of the osteotomy site for
      treatment of distal radius malunions and nonunions using the Agee-Wristjack
      external fixator device. The Agee-Wristjack has several features that make it
      superior to other available small external fixators. Its gear mechanisms confer
      stable distraction of the distal radius following osteotomy and greatly
      facilitate appropriate positioning of the distal fragment. Iliac crest bone graft
      may be harvested and shaped precisely to fit the osteotomy defect. Placement of
      the Agee-Wristjack's distal fixator pins into the index metacarpal instead of the
      distal radius fragment facilitates application of a plate, with minimal
      interference from the distal pins. Finally, the Agee-Wristjack may be maintained
      following surgery to supplement the internal fixation.

PMID- 16092816
TI  - Diagnosis and treatment of longitudinal instability of the forearm.
AB  - Radio-ulnar dissociation can result from high-injury trauma that the compressive
      forces traverse the wrist forearm and elbow. This injury can be thought of as an
      "unhappy triad" of radial head fracture, triangular fibrocartilage complex
      failure, and a tear of the interosseous membrane. The radius is the primary
      stabilizer of the forearm with the forearm interosseous membrane enabling load
      sharing between the radius and the ulna. The central one-third of the
      interosseous membrane is 3 times stronger than the membranous portion and
      approaches the strength of the anterior cruciate ligament for determining
      interosseous membrane injury. Imaging studies with proven diagnostic efficacy
      include magnetic resonance imaging and ultrasound. Surgical treatment should be
      considered when circumstances imply longitudinal instability of the forearm.
      Surgical treatment includes open reduction/internal fixation or prosthetic
      replacement of the radial head as well as repair of the disrupted triangular
      fibrocartilage complex. Successful treatment of radioulnar dissociation is
      predicated on early diagnosis of the condition.

PMID- 16092817
TI  - Capsulodesis of the wrist for scapholunate dissociation.
AB  - We have had favorable results with our early experience using the Mayo
      modification of the dorsal intercarpal ligament capsulodesis. Our early
      experience with this technique has shown improvement in carpal alignment and pain
      relief with the tradeoff of a mild loss of wrist flexion. These results compare
      with reported results of the various capsulodesis techniques in evolution.
      Attention must also be paid as to the stage of dissociation at time of surgery.
      Dynamic dissociation has been treated with capsulodesis alone, whereas a
      combination of ligament repair in conjunction with dorsal intercarpal ligament
      capsulodesis is used to treat both dynamic and static variants. Many other
      investigators report improvements in scapholunate alignment and improvement in
      pain relief and function with a loss of wrist flexion as a tradeoff. However,
      despite technical advances in surgical technique and intraoperative improvement
      of alignment and gapping, these results may diminish by the 2- to 3-year
      postoperative period. Scapholunate interosseous injuries remain a challenging
      problem to even experienced hand and upper extremity surgeons. The Mayo
      modification of the modified dorsal intercarpal ligament capsulodesis is a
      technique that may be added to the armamentarium of treatment of this pathologic
      entity.

PMID- 16092818
TI  - The aesthetic mini wrap-around technique for thumb reconstruction.
AB  - In the past 12 years, 16 thumb defects at, or distal to, the interphalangeal
      joint were reconstructed using a great toe mini wrap-around flap. A flap
      including the entire nail and most of the distal phalanx of the great toe was
      used. Fifteen of the grafts survived. The sensory recovery of the reconstructed
      thumb was good as assessed by 2-point discrimination test with an average of 10
      mm (range 5-15), and there were no complaints of cold intolerance. This technique
      results in good cosmetic appearance, and all patients were pleased with the
      cosmetic aspect of the thumb and there was no significant morbidity at the great
      toe donor site. The final decision to reconstruct a distal thumb amputation is
      influenced by gender, job, and age of the patients. The great toe mini wrap
      around flap is an excellent reconstruction technique in selected patients.

PMID- 16092819
TI  - The reverse radial forearm flap for soft tissue reconstruction of the wrist and
      hand.
AB  - Soft tissue defects of the upper extremity must be carefully assessed to
      determine the most appropriate method of coverage. Direct closure and local flaps
      represent the most basic techniques on the reconstructive ladder; however, they
      are inadequate for large or complex defects. Split thickness skin grafts are
      appropriate for granulating wounds with a bed of vascularized tissue; however, if
      there is an exposed joint or bone devoid of periosteum or tendon devoid of
      paratenon, there will be insufficient neovascularization, and the graft will
      inevitably fail. The reconstructive hand surgeon must then pursue more
      complicated techniques for wound coverage based upon knowledge of the available
      pedicled and free flaps. The reverse radial forearm flap potentially offers thin,
      mobile skin with similar characteristics to the skin over the dorsum of the hand.
      This flap is more versatile than the groin flap and probably more reliable than
      the posterior interosseous artery flap for coverage of moderate-sized defects of
      the dorsal or palmar wrist and hand and is specifically indicated for coverage of
      degloving injuries of the dorsal wrist and hand, after release of thumb-index
      finger web space, and for coverage of amputations of the thumb in preparation for
      toe-to-thumb transfer.

PMID- 16092820
TI  - Subtotal medial epicondylectomy as a surgical option for treatment of cubital
      tunnel syndrome.
AB  - Ulnar nerve compression at the elbow is commonly accepted as the second most
      frequent compressive peripheral neuropathy. The unique anatomic location of the
      ulnar nerve directly posterior to the medial epicondyle at the elbow places it at
      risk for injury. With normal motion of the elbow, the ulnar nerve is subjected to
      compression, traction, and frictional forces. Compression can occur at any of the
      5 sites that begin proximally at the arcade of Struthers and end distally where
      the nerve exits the flexor carpi ulnaris in the forearm. Initial treatment of
      compressive neuropathy is nonoperative, usually consisting of rest, modification,
      and/or restriction of elbow or wrist movement. If symptoms persist, especially
      when accompanied by muscle weakness, surgery is usually indicated. Surgical
      options include decompression in situ, medial epicondylectomy, transposition of
      the ulnar nerve (subcutaneous, intramuscular, or submuscular), and/or a
      combination of these procedures. Careful decompression with a subtotal medial
      epicondylectomy is a valuable procedure that allows decompression at all levels
      with minimal risk of devascularizing the nerve or creating elbow instability.

PMID- 16092821
TI  - Brachioradialis transposition for elbow extension in obstetrical brachial plexus
      palsy.
AB  - Disorders of elbow extension occur following traumatic or neurologic injuries of
      the triceps muscle. Restoration of elbow extension is an integral part of the
      entire upper extremity surgical reconstruction to improve the following daily
      activities: bringing down an object from above, handwriting, using the hand in
      the supine position, steering a wheelchair, driving a car, and swimming. The
      transfer of the posterior head of the deltoid muscle to triceps (Moberg
      procedure) and the transfer of the biceps to triceps (Friedenberg procedure) are
      previously described procedures for the functional restoration of triceps
      function. In conditions where these procedures cannot be used, we describe a new
      technique for restoration of elbow extension. In 4 cases with obstetrical palsy
      sequela, where shoulder abduction was established with the latissimus dorsi and
      teres major transfer, restoration of elbow extension was planned to aid in
      activities performed while the hand is above the head. To achieve this goal, the
      brachioradialis muscle was transposed bipedically to the triceps muscle.

PMID- 16092822
TI  - Sometimes a little is a lot.

PMID- 16092823
TI  - Mechanochemistry: the mechanical activation of covalent bonds.

PMID- 16092824
TI  - Linking multiple bonds between metal atoms: clusters, dimers of "dimers", and
      higher ordered assemblies.

PMID- 16092825
TI  - Pulsed gradient spin-echo (pgse) diffusion and 1H,19F heteronuclear Overhauser
      spectroscopy (HOESY) NMR methods in inorganic and organometallic chemistry:
      something old and something new.

PMID- 16092826
TI  - Quantum mechanical continuum solvation models.

PMID- 16092827
TI  - Organic reactions in aqueous media with a focus on carbon-carbon bond formations:
      a decade update.

PMID- 16092828
TI  - Alpha,beta-diamino acids: biological significance and synthetic approaches.

PMID- 16092829
TI  - Solid-phase synthesis of bicyclic dipeptide mimetics by intramolecular
      cyclization of alcohols, thiols, amines, and amides with N-acyliminium
      intermediates.
AB  - A general strategy for the solid-phase synthesis of structurally diverse bicyclic
      dipeptide mimetics is presented. Depending on the amino acid side-chain (R(1)),
      peptide-derived N-acyliminium intermediates may undergo nucleophilic attack from
      either side-chain functional groups (-OH, -NH(2), -SH, and -CONH(2)) or the amide
      backbone (-CONH-) of the peptide, thus affording a range of aza-, thia-, and
      oxabicycloalkanes in excellent purity and diastereoselectivity. [reaction: see
      text]

PMID- 16092830
TI  - Catalytic asymmetric ring opening of 2,3-substituted norbornenes with
      organometallic reagents: a new formal aza functionalization of cyclopentadiene.
AB  - An unprecedented regioselective and anti stereoselective asymmetric ring opening
      of 1,3-cyclopentadiene-heterodienophile cycloadducts, including also 2,3
      diazabicyclo[2.2.1]heptenes, with hard alkylmetals and copper-phosphoramidite
      catalysts, is reported. The induced ring opening, in conjunction with C-C bond
      formation, gives a catalytic and practical access to new heterofunctionalized
      cyclopentenes in an enantioenriched form (up to 86% ee). [reaction: see text]

PMID- 16092831
TI  - Samarium-promoted coupling of pyridine-based heteroaryl analogues of benzylic
      acetates with carbonyl compounds.
AB  - 2-Substituted pyridine, quinoline, isoquinoline, bipyridine, and 1,10
      phenanthroline analogues of benzylic acetates undergo SmI(2)-promoted coupling
      with aldehydes and ketones to afford (2-hydroxyalkyl)heteroaromatics. [reaction:
      see text]

PMID- 16092832
TI  - N-acyl derivatives of arginine and tryptophan isolated from environmental DNA
      expressed in Escherichia coli.
AB  - Heterologous expression of microbial DNA extracted directly from environmental
      samples (environmental DNA, eDNA) in easily cultured hosts can provide access to
      natural products produced by previously uncultured bacteria. This report
      describes the characterization of antibacterially active long-chain N-acyl
      derivatives of tryptophan and arginine that are produced by eDNA clones hosted in
      Escherichia coli. The sequencing and subcloning of the proposed N-acyl amino acid
      synthases (NASs) for each family of natural products are also described.
      [reaction: see text]

PMID- 16092833
TI  - Synthesis of the aglycones of altromycins and kidamycin from a common
      intermediate.
AB  - The aglycone structures 1 and 2, respectively corresponding to the antitumor
      antibiotic natural products altromycin and kidamycin, have been efficiently
      synthesized from a common advanced intermediate 3. A series of Claisen
      condensations and aromatizations affords the anthracene section of 3, followed by
      annulation of the pyrone ring. The functional groups of 3 can be manipulated for
      enantioselective introduction of the epoxide side-chain of altromycin aglycone 1,
      as well as synthesis of the kidamycin aglycone 2. [reaction: see text]

PMID- 16092834
TI  - Synthesis of the branched C-glycoside substructure of altromycin B.
AB  - Tungsten-catalyzed cycloisomerization of alkynyl alcohols including 8 provides
      only the endocyclic enol ether (11) as a key intermediate for the branched C
      glycoside substructure (2) of altromycin B. A sequence of Stille cross-coupling
      reaction and regio- and stereoselective functional group transformations affords
      each C13-diastereomer of the branched C-arylglycoside (2a and 2b). [reaction: see
      text]

PMID- 16092835
TI  - Facile dearomatizing radical arylation of furan and thiophene.
AB  - In the presence of catalytic diphenyl diselenide, reduced in situ to
      benzeneselenol, tributyltin hydride and V-70 promote the addition of aryl iodides
      to furan and thiophene. The adduct radicals are trapped by the selenol to give
      the 2-aryl-2,3-dihydro and 2-aryl-2,5-dihydro heterocyclic products. When the
      iodide is an o-iodophenol, a cyclization follows the radical addition and
      provides bridged bicyclic acetals. [reaction: see text]

PMID- 16092836
TI  - A new practical one-pot conversion of phenols to anilines.
AB  - A novel one-pot synthesis of anilines from phenols was developed. Using this
      methodology, anilines are produced in good yield (86%) by a reaction of phenols
      with 2-bromo-2-methylpropionamide and NaOH in DMA via Smiles rearrangement.
      Phenols, which are substituted electron-withdrawing groups, are more reactive for
      Smiles rearrangement. Thiophenols are also converted to anilines. The process is
      a convenient, safe, and inexpensive method for large-scale preparation of
      anilines. [reaction: see text]

PMID- 16092837
TI  - Catalytic asymmetric desymmetrization of cyclic meso-1,3- and 1,4-diols by a
      phosphinite derivative of quinidine.
AB  - Asymmetric monobenzoylation reactions of cyclic meso-1,3- and 1,4-diols were
      catalyzed by a phosphinite derivative of quinidine to afford the corresponding
      monobenzoylated diol with good yield and enantioselectivity. [reaction: see text]

PMID- 16092838
TI  - Allyl sulfones as precursors to allylzincs in the palladium-catalyzed zinc-ene
      cyclization: highly efficient synthesis of enantiopure (-)-erythrodiene.
AB  - Easily prepared allyl phenyl sulfones, capable of introduction of the alkene by
      electrophilic alpha-substitution, are superior to allyl acetates as substrates
      for Pd-catalyzed Zn-ene cyclizations, providing C5 or C(4)N rings with cis-1,2
      vinyl and -CH(2)Zn substituents. Several examples, with different methods of
      substrate preparation, are presented. [reaction: see text]

PMID- 16092839
TI  - Unprecedented alkene stereocontrol in the Claisen rearrangement of cyclic bis
      allylic esters.
AB  - The Ireland and ester enolate Claisen rearrangements of tertiary substituted bis
      allylic esters derived from cyclohexenones afford pentenoic acids that possess
      tri- and tetrasubstituted alkylidenes with unprecedented levels of
      stereoselectivity. In some cases the higher energy exocyclic alkene is the major
      product. [reaction: see text]

PMID- 16092841
TI  - Highly chemoselective addition of amines to epoxides in water.
AB  - Aminolysis of a variety of epoxides by aliphatic and aromatic amines in water, in
      the absence of any catalyst with high yields, is reported. Beta-amino alcohols
      were formed under mild conditions with high selectivity and in excellent yields.
      [reaction: see text]

PMID- 16092840
TI  - Stereoselective assembly of a 1,3-diene via coupling between an allenic acetate
      and a (B)-alkylborane: synthetic studies on amphidinolide B1.
AB  - The preparation of three fragments for the total synthesis of amphidinolide B1
      has been described. The C16 stereochemistry was set by asymmetric allylic
      alkylation. C21 and C25 stereogenic centers were set by an
      enantioselective/diastereoselective double allylation reaction. The C9
      configuration was set by an asymmetric heteroene reaction. A differentially
      substituted stereodefined 1,3-diene iodide was synthesized by iodide-mediated
      S(N)2' reaction. A novel stereoselective method to assemble a 1,3-diene by
      coupling an allenic acetate and (B)-alkylborane is also reported. [structure: see
      text]

PMID- 16092842
TI  - An enantioselective entry to cis-perhydroisoquinolines.
AB  - An enantioselective route to cis-perhydroisoquinolines, involving a
      cyclocondensation reaction of (R)-phenylglycinol with a racemic oxoester, a
      stereoselective conjugate addition to an unsaturated bicyclic lactam, and the
      closure of the carbocyclic ring by a ring-closing metathesis as the key steps is
      reported. This route allows the preparation of 3-cyano derivatives as well as cis
      octahydroisoquinolines bearing a quaternary center at the C4-position. [reaction:
      see text]

PMID- 16092843
TI  - Catalytic coupling of C-H and C-I bonds using pyridine as a directing group.
AB  - A method for the palladium-catalyzed arylation of pyridines and pyrazoles has
      been developed. Both aliphatic and aromatic C-H bonds may be functionalized using
      this method. A bromo substituent is tolerated on the aryl iodide coupling
      component. [reaction: see text]

PMID- 16092844
TI  - Chromophoric binaphthyl derivatives.
AB  - A short synthetic route is outlined, starting from bromo-BN derivatives, via
      halogen lithium exchange, subsequent Michael reaction with dimethylaminoacrolein,
      hydrolysis to the corresponding aldehyde, and final condensation with a
      benzothiazolium unit to produce a BN-pentamethinium system, which absorbs in the
      visible range around 450 nm. Enantiopure ligands show a decent Cotton effect in
      the CD spectrum. Preliminary data show potential of these compounds in the area
      of supramolecular chemistry (enantioselective recognition) and also for medicinal
      application (induction of apoptosis). [reaction: see text]

PMID- 16092845
TI  - Solvent effects on hydrogen abstraction reactions from lactones with antioxidant
      properties.
AB  - Solvent effects on the kinetics for hydrogen abstraction from a lactone
      antioxidant were determined for alkoxyl and nitroxyl radicals; their reactivity
      differ by about 7 orders of magnitude. A decrease by approximately 12 and
      approximately 35 were determined for H-abstraction by tert-butoxyl and nitroxyl
      radicals, respectively, upon changing the solvent from hexane to acetonitrile.
      Results of solvent and isotope studies indicate that the antioxidant properties
      of lactone antioxidants should be attributed to the enol, not the lactone.
      [reaction: see text]

PMID- 16092846
TI  - 9-(cycloheptatrienylidene)-fluorene derivative: remarkable ratiometric pH sensor
      and computing switch with NOR logic gate.
AB  - 2,7-Bis(4-dimethylaminophenyl)-9-(cycloheptatrienylidene)fluorene (1) was
      synthesized and characterized. 1 could be used as a fluorescent sensor either for
      pH or for pyridinium halide. Integrated with the ratiometric method and an NOR
      logic gate, a tunable two-input/multi-output system was presented on the basis of
      this single molecule. [structure: see text]

PMID- 16092847
TI  - Cyclization of lithiated pyridine and quinoline carboxamides: synthesis of
      partially saturated pyrrolopyridines and spirocyclic beta-lactams.
AB  - Lithiation of N-benzyl pyridine and quinoline carboxamides alpha to nitrogen
      gives anions that undergo intramolecular attack on the pyridine or quinoline
      ring, either directly or on activation of the ring by N-acylation. The resulting
      four-, five-, or six-membered-ring-containing compound may be oxidized,
      protonated, alkylated, or acylated to give a range of polycyclic heterocycles,
      including pyrrolopyridines, pyrroloquinolines, benzonaphthyridines, and
      azaspirocyclic beta-lactams. [reaction: see text]

PMID- 16092848
TI  - Increasing fluorous partition coefficients by solvent tuning.
AB  - Low partition coefficients of fluorous components have been a persistent problem
      in liquid-liquid separations using perfluoroalkanes as the fluorous phase.
      Solvent tuning of both the nonfluorous and the fluorous phase dramatically
      enhances the partitioning of light or polar fluorous molecules into the fluorous
      liquid phase, while minimally effecting partition coefficients of nonfluorous
      molecules. These findings suggest an expanded scope for liquid-based separations
      in fluorous biphasic catalysis, fluorous-tagged reagents, fluorous-supported
      oligomer synthesis, and related areas. [reaction: see text]

PMID- 16092849
TI  - Ruthenium-catalyzed [2 + 2] cycloadditions of ynamides.
AB  - Ruthenium-catalyzed [2 + 2] cycloadditions between norbornene and ynamides were
      investigated. The ynamide moiety was found to be compatible with the ruthenium
      catalyzed cycloaddition conditions, giving the corresponding cyclobutene
      cycloadducts in moderate to good yields (up to 97%). [reaction: see text]

PMID- 16092850
TI  - Stereocontrolled assembly of tetrasubstituted tetrahydrofurans: a concise
      synthesis of virgatusin.
AB  - The condensation of substituted allylsiloxanes with aldehydes leads to the highly
      stereoselective construction of 2,3,4,5-tetrasubstituted tetrahydrofurans. With
      electron-rich aryl and alpha,beta-unsaturated aldehydes as substrates, the
      stereochemical outcome at C5 can be dictated by appropriate choice of Lewis acid.
      The reaction has been applied to a concise (nine step) synthesis of (+)
      virgatusin (ent-1). [reaction: see text]

PMID- 16092851
TI  - Copper(II)-catalyzed aerobic oxidation of primary alcohols to aldehydes in ionic
      liquid [bmpy]PF6.
AB  - A room-temperature aerobic oxidation of primary alcohols to aldehydes catalyzed
      by the three-component system acetamido-TEMPO/Cu(ClO(4))(2)/DMAP in the ionic
      liquid [bmpy]PF(6) has been developed, and the catalysts can be recycled and
      reused for five runs without any significant loss of catalytic activity.
      [reaction: see text]

PMID- 16092852
TI  - Parity and heteroatom effects on open-shell exchange interactions: nitrenophenyl
      iminoylnitroxides.
AB  - Photolysis of pN3PhIN and mN3PhIN in frozen matrix yields pNPhIN and mNPhIN,
      respectively. pNPhIN gives a quartet state with nonlinear ESR intensity behavior
      (|D/hc| = 0.300 cm(-1), |E/hc| congruent with 0.0 cm(-1)); mNPhIN gives a
      thermally excited quartet state (|D/hc| = 0.336 cm(-1), |E/hc| = 0.006 cm(-1))
      with inverse Curie behavior. Computations show little nitrene delocalization onto
      the radicals even for the para system. The NPhIN systems behave differently from
      analogous nitronylnitroxides due to asymmetric radical spin distribution.
      [reaction: see text]

PMID- 16092853
TI  - GaCl3-catalyzed insertion of isocyanides into a C-O bond in cyclic ketals and
      acetals.
AB  - The reaction of cyclic ketals or acetals with 2,6-dibromophenylisocyanide in the
      presence of a catalytic amount of GaCl(3) results in the insertion of isocyanide
      into the carbon-oxygen bond of cyclic ketals and acetals. [reaction: see text]

PMID- 16092854
TI  - 1-substituted beta-carbolines by a Pictet-Spengler cyclization with thioortho
      esters and carbon-carbon bond formation via N-sulfonyl iminium ions generated
      from N,S-sulfonyl acetals.
AB  - The reaction of N-tosyltryptamines with thioortho esters, leading to 1
      thiosubstituted tetrahydro-beta-carbolines under modified Pictet-Spengler
      conditions, is described. The 1-heterosubstituted beta-carbolines furnished 1
      substituted beta-carbolines upon reaction with Grignard reagents and silyl
      derivatives under Lewis acid promotion. [reaction: see text]

PMID- 16092855
TI  - A novel oxidative rearrangement of 6-methoxypyran-2-ones.
AB  - As part of our continuing studies of pyrone-containing natural products, a series
      6-methoxypyran-2-ones were synthesized. These were found to react with molecular
      oxygen at 20 degrees C, and this novel reaction yielded a series of highly
      functionalized alpha,beta-butenolides. [reaction: see text]

PMID- 16092856
TI  - Exploring an expedient IMDA reaction approach to construct the guanacastepene
      core.
AB  - Construction of the [5-7-6] tricyclic core of guanacastepenes was attempted by
      using the intramolecular Diels-Alder (IMDA) reaction and Me(3)Al-mediated ring
      opening of the oxabridge as key synthetic steps. The illustrated chemistry
      demonstrated a synthetic feasibility to build up the framework of guanacastepenes
      by the IMDA reaction. [reaction: see text]

PMID- 16092857
TI  - Stereospecific route to 5,11-methanomorphanthridine alkaloids via intramolecular
      1,3-dipolar cycloaddition of nonstabilized azomethine ylide: formal total
      synthesis of (+/-)-pancracine.
AB  - The core structure of the complex pentacyclic 5,11-methanomorphanthridine
      alkaloids is constructed stereospecifically in one step employing an
      intramolecular [3 + 2]-cycloaddition of nonstabilized azomethine ylide as the key
      step. The strategy is demonstrated by accomplishing the formal total synthesis of
      (+/-)-pancracine. [reaction: see text]

PMID- 16092858
TI  - Improved synthesis of 2,2'-dibromo-9,9'-spirobifluorene and its 2,2'-bisdonor
      7,7'-bisacceptor-substituted fluorescent derivatives.
AB  - Pure 2,2'-Dibromo-9,9'-spirobifluorene was synthesized by a method that did not
      involve troublesome dibromination of 9,9'-spirobifluorene or Sandmeyer reaction
      of 2,2'-diamino-9,9'-spirobifluorene. A series of donor-acceptor orthogonally
      substituted 9,9'-spirobifluorene was subsequently prepared showing rich variation
      of fluorescence in solution and in solid state. [reaction: see text]

PMID- 16092859
TI  - Efficient synthesis and structural characteristics of zwitterionic twisted pi
      electron system biaryls.
AB  - A series of unconventional twisted pi-electron system molecules has been
      synthesized via Suzuki cross-coupling of two sterically hindered arenes.
      Crystallographic analysis of these molecules reveals a large ring-ring dihedral
      twist angle (87 degrees ) and a highly charge-separated zwitterionic ground
      state. An efficient conversion of phenols into aryl halides is also reported.
      [reaction: see text]

PMID- 16092860
TI  - Efficient construction of the oxatricyclo[6.3.1.0(0,0)]dodecane core of
      komaroviquinone using a cyclization/cycloaddition cascade of a rhodium carbenoid
      intermediate.
AB  - The rhodium(II)-catalyzed cyclization/cycloaddition cascade of a o
      carbomethoxyaryl diazo dione is described as a potential route to the
      oxatricyclo[6.3.1.0(0,0)]dodecane substructure of the icetexane diterpene
      komaroviquinone. The initially formed carbonyl ylide dipole prefers to cyclize to
      an epoxide at 25 degrees C but can be induced to undergo cycloaddition across the
      tethered pi-bond at higher temperatures. [reaction: see text]

PMID- 16092861
TI  - Photochemical cyclization with release of carboxylic acids and phenol from
      pyrrolidino-substituted 1,4-benzoquinones using visible light.
AB  - Visible light irradiation of 5-acyloxymethyl- and 5-phenoxymethyl-2-pyrrolidino
      1,4-benzoquinones effects photoisomerization to labile oxazolidines, which
      undergo elimination of carboxylate or phenolate leaving groups in high yields to
      generate trappable o-quinone methide intermediates. [reaction: see text]

PMID- 16092862
TI  - Regulation of stereoselectivity using Lewis acid in the cyclization of allenic
      aldehydes catalyzed by palladium complex.
AB  - A highly diastereoselective synthesis of 3 is achieved from the reaction of 1
      with hexamethylditin catalyzed by palladium complex in the presence of 20 mol %
      tris(pentafluorophenyl)borane as a Lewis acid additive for a reversal of
      diastereoselectivity, whereas 2 is formed in the absence of Lewis acid additive.
      The method described herein is successful with various substrates 1 in good
      yields and high levels of diastereoselectivity. [reaction: see text]

PMID- 16092863
TI  - Efficient stereochemical controllers in biaryl Suzuki coupling reactions:
      benzylic carbinols bearing in beta-position thioether, dimethylamino, or
      sulfoxide groups.
AB  - Highly atropo-diastereoselective Suzuki coupling between aryl halides bearing
      stereogenic benzylic carbinols with sulfoxide, thioether, or dimethylamino groups
      as efficient internal chelating ligands and 2-methoxy-1-naphthylboronic acid were
      performed with high yields; a palladacycle is proposed as a potential transition
      state. [reaction: see text]

PMID- 16092864
TI  - Tandem catalytic carbene addition/bicyclization of enynes. One-step synthesis of
      fluorinated bicyclic amino esters by ruthenium catalysis.
AB  - The reaction of diazo compounds with enynes, containing a fluorinated amino acid
      moiety, in the presence of the precatalyst Cp(Cl)Ru(COD) leads to fluorinated
      alkenyl bicyclo[3.1.0]hexane and [4.1.0]heptane amino acid derivatives. It is
      remarkable that the catalyst, in situ generated from ruthenium complex and diazo
      compound, completely inhibits the ring closing metathesis of enyne to the profit
      of tandem alkenylation/cyclopropanation with high stereoselectivity. The study
      shows that the Cp(Cl)Ru moiety in ruthenacyclobutane favors reductive elimination
      versus expected alkene metathesis. [reaction: see text]

PMID- 16092865
TI  - Enantioselective total synthesis of (-)-candelalide A, a novel blocker of the
      voltage-gated potassium channel Kv1.3 for an immunosuppressive agent.
AB  - A convergent route to (-)-candelalide A involved the union of a trans-decalin
      portion (AB ring) and a gamma-pyrone moiety through the C16-C3' bond to assemble
      the whole carbon framework and subsequent formation of the dihydropyran ring (C
      ring) as the crucial steps. A strategic [2,3]-Wittig rearrangement was employed
      for establishing the stereogenic center at C9 and an exo-methylene function at C8
      present in the decalin portion. [reaction: see text]

PMID- 16092866
TI  - Directed ortho lithiation of N-alkylphenylaziridines.
AB  - The ortho lithiation-trapping sequence of phenylaziridines is described. This
      methodology, which counts on the ability of the aziridino group to act as a
      directed metalation group (DMG), provides an easy access to functionalized
      arylaziridines as well as to phthalans and phthalides. The importance of the
      aziridine N-substituent in this DoM reaction is stressed as well. [reaction: see
      text]

PMID- 16092867
TI  - Pentaerythritol as the core of multivalent glycolipids: synthesis of a glycolipid
      with three SO3Lea ligands.
AB  - A glycolipid containing three SO(3)Le(a) ligands was synthesized with
      pentaerythritol as the core. The glycolipid was used to prepare glycoliposomes
      that showed stability similar to that of DSPC liposomes without glycolipid. The
      easily prepared derivatives of pentaerythritol proved to be useful scaffolds for
      multivalent displaying of carbohydrates in the form of glycolipids and clustered
      glycoliposomes. [structure: see text]

PMID- 16092868
TI  - Cu(I)-catalyzed direct enantioselective cross aldol-type reaction of
      acetonitrile.
AB  - Direct catalytic enantioselective cross aldol-type reaction of an acetate
      surrogate was developed using Cu alkoxide-chiral phosphine complexes as
      catalysts. Chemoselective activation and deprotonation of the donor substrate
      (acetonitrile) by the soft metal alkoxide in a strongly donating solvent (HMPA)
      are key to success in this reaction. Useful chemical yields and promising
      enantioselectivities are produced using either DTBM-SEGPHOS or a tuned BIPHEP as
      a chiral ligand. [reaction: see text]

PMID- 16092869
TI  - Solid-phase synthesis of N-formylhydroxylamines (reverse/retro-hydroxamates).
AB  - N-Formylhydroxylamines, also known as reverse- or retro-hydroxamates, have become
      of significant interest in the recent past as inhibitors of metalloenzymes.
      Although solution-phase synthetic routes to such compounds have been reported,
      these are often lengthy and involve purification at each stage. Herein, novel
      three-step solid-phase synthetic approaches are described that enable libraries
      of such compounds to be produced in a convergent and efficient manner using
      commercially available starting materials. [reaction: see text]

PMID- 16092870
TI  - 3,3'-disubstituted BINAP ligands: synthesis, resolution, and applications in
      asymmetric hydrogenation.
AB  - A novel family of BINAP ligands were prepared with alkoxy- and acetoxy-derived
      substituents in the 3,3'-positions. They were prepared through a convergent
      synthesis starting from readily available 4-bromo-2-naphthol. These ligands
      afforded excellent enantioselectivities in the asymmetric hydrogenation of
      substituted olefins. The presence of the 3,3'-substituents was shown to be
      beneficial by a direct comparison with the parent unsubstituted BINAP. [reaction:
      see text]

PMID- 16092871
TI  - One-step assembly of functionalized gamma-butyrolactones from benzoins or
      benzaldehydes via an N-heterocyclic carbene-mediated tandem reaction.
AB  - We describe here a direct, efficient, one-step construction of gamma,gamma
      difunctionalized gamma-butyrolactones from benzoins or benzaldehydes via a tandem
      reaction promoted by 1,3-dimethyl imidazolin-2-ylidene, an N-heterocyclic carbene
      (NHC). [reaction: see text]

PMID- 16092872
TI  - Preparation of 13C4-6-methyl anthranilic ester via a Diels-Alder-type process. an
      experimental and theoretical study to characterize an unexpected isotope
      exchange.
AB  - Buta-2,3-dienoate reacts with vinyl ketenimine to give the corresponding
      substituted aniline through a Diels-Alder cycloaddition. Besides the expected
      Diels-Alder adduct 3a, the aniline 3b was also obtained in a ratio of 91:9. The
      observed (13)C exchange is explained on the basis of a reversible [2 + 2]
      cycloaddition competing with the [4 + 2] process. This is supported by B3LYP DFT
      computations, as a stepwise pathway lies very close in energy to the [4 + 2]
      concerted one. [reaction: see text]

PMID- 16092873
TI  - Effect of imino nitroxyl and nitronyl nitroxyl groups on the photochromic
      reactivity of diarylethenes.
AB  - Diarylethene derivatives having imino nitroxide and nitronyl nitroxide have been
      prepared to examine the effect of the radical substituents on the photochromic
      reactivity of 1,2-bis(2-methyl-1-benzothiophen-3-yl)perfluorocyclopentene. These
      radical substituents reduce the quantum yields of both cyclization and
      cycloreversion reactions. The nitronyl nitroxyl moiety is more effective to
      suppress the reactivity in comparison with the imino nitroxide moiety. [reaction:
      see text]

PMID- 16092874
TI  - Enantioselective Bronsted acid catalyzed transfer hydrogenation: organocatalytic
      reduction of imines.
AB  - The first enantioselective Bronsted acid catalyzed reduction of imines has been
      developed. This new organocatalytic transfer hydrogenation of ketimines with
      Hantzsch dihydropyridine as the hydrogen source offers a mild method to various
      chiral amines with high enantioselectivity. The stereochemistry of the chiral
      amines can be rationalized by a stereochemical model derived from an X-ray
      crystal structure of a chiral BINOL phosphate catalyst. [reaction: see text]

PMID- 16092875
TI  - Triple helicate constructed by covalent bondings: crystal structure and effective
      synthesis based on propeller-like substructures.
AB  - A triple helicate, having a macrocyclic aromatic amide structure, was synthesized
      in high yield because of a preorganized component of the tertiary
      benzenetrianilide moieties in a propeller-like syn conformation at both ends. The
      helicity was derived from tilted T-shaped aromatic-aromatic (CH-pi) interactions
      between each of the N-phenyl rings. [structure: see text]

PMID- 16092876
TI  - Stereoselective functionalization of cyclopropane derivatives using
      bromine/magnesium and sulfoxide/magnesium exchange reactions.
AB  - The reaction of 2,2-dibromo-1-methyl-cyclopropanecarbonitrile (1) with i-PrMgCl
      in Et(2)O/CH(2)Cl(2) provides the cis-magnesium-carbenoid (2), which reacts with
      high retention of configuration with various electrophiles. If E = SPh, a
      stereoselective generation of a quaternary center via a sequential Br/Mg- and
      sulfoxide/Mg-exchange can be achieved. [reaction: see text]

PMID- 16092877
TI  - [2.2]paracyclophane/dehydroannulene hybrids: probing the aromaticity of the
      dehydro[14]annulene framework.
AB  - The synthesis of [2.2]paracyclophane/dehydro[14]annulene hybrids 1 and 2 is
      reported. Comparison of the proton NMR spectra of 1 and 2 with their open
      precursors and with related model compounds reveals the pronounced effect of
      macrocycle formation upon the cyclophane protons H15/H16, which lie above the
      shielding cone of the diatropic [14]annulene moiety. [structure: see text]

PMID- 16092878
TI  - A novel three-component one-pot reaction involving alkynes, urea or thiourea, and
      aldehydes.
AB  - A novel three-component, one-pot condensation yielding 2-amino-4H-1,3-oxazines or
      2-amino-4H-1,3-thiazines from alkynes, urea or thiourea, and aldehydes is
      described. [reaction: see text]

PMID- 16092879
TI  - Chemoselective arylamidine cyclizations: mild formation of 2-arylimidazole-4
      carboxylic acids.
AB  - A versatile, one-pot synthesis of 2-arylimidazole-4-carboxylic acids from
      arylamidines and methyl-2-chloroacetoacetate is described. The transformation is
      chemoselective, and reaction conditions are mild. Moreover, the flexibility of
      the strategy offers rapid access to two important classes of biaryl compounds,
      both 2-arylimidazoles and 2-arylpyrimidines, depending simply upon solvent and
      base selection. [reaction: see text]

PMID- 16092880
TI  - The first Negishi cross-coupling reaction of two alkyl centers utilizing a Pd-N
      heterocyclic carbene (NHC) catalyst.
AB  - The development of an NHC-based system capable of cross-coupling sp(3)-sp(3)
      centers in high yield has been a long-standing challenge. This communication
      describes the use of a Pd-NHC catalytic system that achieves room-temperature
      Negishi cross-couplings of unactivated, primary bromides and alkyl organozinc
      reagents with a variety of functionality. [reaction: see text]

PMID- 16092881
TI  - Efficient asymmetric synthesis of (+)-SCH 351448.
AB  - An efficient and stereocontrolled total synthesis of (+)-SCH 351448, a novel
      activator of low-density lipoprotein receptor promoter, has been achieved with a
      longest linear sequence of 21 steps. Key steps include applications of the
      recently developed asymmetric allyl- and crotylsilane reagents and a new
      protodesilylative version of the tandem silylformylation/allylsilylation
      reaction, which provides an efficient synthesis of 1,5-syn-diols. [reaction: see
      text]

PMID- 16092882
TI  - Sinulochmodins A-C, three novel terpenoids from the soft coral Sinularia
      lochmodes.
AB  - An unprecedented C,C-linked dimeric norcembranoid (sinulochmodin A, 1), a novel
      isocembranoid (sinulochmodin B, 2), and a novel yonarane norditerpenoid
      (sinulochmodin C, 3) were isolated from the soft coral Sinularia lochmodes. The
      structures of these metabolites were elucidated by extensive spectroscopic
      analysis and on the basis of the absolute structures of two related
      norditerpenoids (4 and 5), which were determined for the first time by a modified
      Mosher method. A plausible pathway for the biosynthesis of 1 and 3-5 from 2 was
      postulated. [structure: see text]

PMID- 16092883
TI  - An unusual radical Smiles rearrangement.
AB  - Radicals derived from N-(alpha-xanthyl)acetanilides or N-(alpha
      xanthyl)acetylaminopyridines possessing a substituent next to the nitrogen
      undergo a hitherto undocumented Smiles rearrangement proceeding through a four
      membered ring. It was also found that under certain conditions the amidyl radical
      produced by cleavage of the four-membered ring intermediate can undergo
      fragmentation to give an isocyanate. Such fragmentations are unprecedented at
      temperatures corresponding to refluxing benzene or chlorobenzene. [reaction: see
      text]

PMID- 16092884
TI  - Catalytic asymmetric synthesis with rh-diene complexes: 1,4-addition of
      arylboronic acids to unsaturated esters.
AB  - A general route to enantioenriched tert-butyl 3,3-diarylpropanoates is presented.
      These useful building blocks are prepared via an asymmetric rhodium-catalyzed
      conjugate addition of arylboronic acids to unsaturated tert-butyl esters in the
      presence of chiral dienes as ligands. The addition of both electron-poor and
      electron-rich boronic acids proceeds smoothly with various enoates in 63-90%
      yield with high enantioselectivites (89-94% ee). [reaction: see text]

PMID- 16092885
TI  - My elderly aunt's car accident: a James Bond thriller or a fight for
      independence.

PMID- 16092886
TI  - Asymptomatic lesions isolated to lower back. Patient has undergone radiation
      therapy for tumor of kidney.

PMID- 16092887
TI  - Herb-drug interactions: interactions between ginseng and prescription
      medications.

PMID- 16092888
TI  - Sexual dysfunction in the older woman: complex medical, psychiatric illnesses
      should be considered in evaluation and management.

PMID- 16092889
TI  - Assessing older drivers: a primary care protocol to evaluate driving safety risk.
AB  - Most articles on elder drivers offer either general advice, or review testing
      protocols that divide drivers into two distinct groups: safe or unsafe. We
      believe it is unreasonable to expect any testing to fully separate drivers into
      just these two mutually exclusive groups, so we offer a protocol for a more
      practical approach. This protocol can be applied by primary care physicians. We
      review the justification for the many steps of this protocol, which have branches
      that lead to identifying drivers as low risk, high risk (for accidents) or
      needing further evaluation. Options for further evaluation are provided.

PMID- 16092890
TI  - Giant cell arteritis: diagnosing and treating inflammatory disease in older
      adults.
AB  - Giant cell arteritis (GCA), also known as temporal arteritis, cranial arteritis,
      or granulomatous arteritis, is a systemic necrotizing vasculitis seen in patients
      typically over age 50. If untreated, GCA can cause permanent visual loss in one
      or both eyes in 13% to 50% of patients. Primary care physicians routinely see
      elderly patients with headaches and fatigue; these may be potential symptoms of
      GCA. C-reactive protein (CRP) in conjunction with erythrocyte sedimentation rate
      (ESR) has 97% specificity in diagnosing GCA. Temporal artery biopsy confirms the
      diagnosis in many cases. Early recognition and treatment of this potentially
      blinding condition is thus essential. Systemic steroids are the standard therapy
      for patients with a positive diagnosis of GCA, and in a high percentage of
      patients the treatment may extend for more than one year.

PMID- 16092892
TI  - Abstracts from the 10th Annual CyberTherapy Conference, June 6-10, 2005, Basel,
      Switzerland.

PMID- 16092891
TI  - Functional identification of catalytic metal ion binding sites within RNA.
AB  - The viability of living systems depends inextricably on enzymes that catalyze
      phosphoryl transfer reactions. For many enzymes in this class, including several
      ribozymes, divalent metal ions serve as obligate cofactors. Understanding how
      metal ions mediate catalysis requires elucidation of metal ion interactions with
      both the enzyme and the substrate(s). In the Tetrahymena group I intron, previous
      work using atomic mutagenesis and quantitative analysis of metal ion rescue
      behavior identified three metal ions (MA, MB, and MC) that make five interactions
      with the ribozyme substrates in the reaction's transition state. Here, we combine
      substrate atomic mutagenesis with site-specific phosphorothioate substitutions in
      the ribozyme backbone to develop a powerful, general strategy for defining the
      ligands of catalytic metal ions within RNA. In applying this strategy to the
      Tetrahymena group I intron, we have identified the pro-SP phosphoryl oxygen at
      nucleotide C262 as a ribozyme ligand for MC. Our findings establish a direct
      connection between the ribozyme core and the functionally defined model of the
      chemical transition state, thereby extending the known set of transition-state
      interactions and providing information critical for the application of the recent
      group I intron crystallographic structures to the understanding of catalysis.

PMID- 16092894
TI  - Gender, Internet identification, and Internet anxiety: correlates of Internet
      use.
AB  - This paper reports a study that investigated the effects of gender, Internet
      anxiety, and Internet identification on use of the Internet. The study involved
      608 undergraduate students (490 females and 118 males). We surveyed the students'
      experience with the Internet, as well as their levels of Internet anxiety and
      Internet identification. We found a number of gender differences in participants'
      use of the Internet. Males were proportionally more likely to have their own web
      page than were females. They used the Internet more than females; in particular,
      they were more likely to use game websites, to use other specialist websites, and
      to download material from the Internet. However, females did not use the Internet
      for communication more than males. There was a significant positive relationship
      between Internet identification and total use of the Internet, and a significant
      negative relationship between Internet anxiety and total use of the Internet.
      Controlling for Internet identification and Internet anxiety, we found a
      significant and negative correlation between gender and use of the Internet. In
      total, all three of our predictors accounted for 40% of the variance in general
      Internet use: with Internet identification accounting for 26%, Internet anxiety
      accounting for 11%, and gender accounting for 3%.

PMID- 16092895
TI  - eQuest: case study of a comprehensive online program for self-study and personal
      growth.
AB  - eQuest is an online program that guides participants through a variety of online
      activities in order to help them address some specific personal issue, as well as
      encourage self-insight on a broader level. These activities include locating and
      evaluating information, joining discussion/support groups, establishing one-on
      one relationships with knowledgeable people, experimenting with different types
      of online communication, utilizing and evaluating online psychological tests,
      creating a personal web page, and experimenting with freeform browsing
      techniques. eQuest stimulates integrated learning by encouraging people to
      compare and combine what they discover in these different online activities, and
      to bring their online and offline lifestyles together. It includes
      educational/therapeutic exercises to help people prepare for and benefit from
      these activities. Unlike traditional forms of clinical intervention, in which a
      professional "does" psychotherapy with a client, the eQuest consultant assists
      people through the program, helps them evaluate their experiences, and encourages
      the integration process. Underlying all these therapeutic activities is a
      philosophy that advocates the therapeutic value of developing an online lifestyle
      and integrating it into one's offline life, while also recognizing the potential
      pitfalls of cyberspace.

PMID- 16092899
TI  - Tom Cruise: entertaining or dangerous?

PMID- 16092896
TI  - Effects of group experiential cognitive therapy for the treatment of panic
      disorder with agoraphobia.
AB  - A treatment protocol, called experiential cognitive therapy (ExCT), was
      developed. It integrated traditional cognitive behavior therapy (CBT) with
      virtual reality exposure for the treatment of panic disorder with agoraphobia
      (PDA). The objective of this study was to test the efficacy of short-term (four
      sessions) ExCT compared with a traditional 12-session panic control program (PCP)
      for the treatment of PDA. Forty patients diagnosed as having PDA by the
      diagnostic criteria of DSM-IV were randomly assigned to ExCT and PCP groups of 20
      patients each. The treatment effects were measured with self-report
      questionnaires, including the BDI, STAI, ASI, PBQ, ACQ, and BSQ. The authors also
      assessed high end-state functioning (HES), including the success rate of stopping
      or reducing medication at post-treatment and 6-month follow-up. In all ratings,
      both ExCT and PCP groups showed significant improvement post-treatment compared
      with pre-treatment scores. There were no significant differences between the two
      treatment groups in HES and medication discontinuation at post-treatment, but
      there was a significant difference in medication discontinuation at 6-month
      follow-up. These results suggested that although short-term effectiveness of ExCT
      might be comparable to the effectiveness of PCP, long-term effectiveness of ExCT
      might be relatively inferior to the effectiveness of PCP.

PMID- 16092900
TI  - Psychopharmacology news.

PMID- 16092901
TI  - Diagnostically homeless and needing appropriate placement.

PMID- 16092902
TI  - Barbara Fish: the Bellevue years.

PMID- 16092903
TI  - Abnormal infant neurodevelopment predicts schizophrenia spectrum disorders.
AB  - OBJECTIVE: The aim of this study was to detect infants who carry a schizophrenic
      genotype and study the development of schizophrenia spectrum disorders (SZSD)
      from birth. INTRODUCTION: In the 1940s, Bender described uneven maturation in
      childhood schizophrenics and in 1952 found this in the infant histories of 6
      schizophrenic children. METHODS: We tested a possible index for defective neural
      integration in infants termed "pandysmaturation" (PDM). This required retarded
      cranial growth plus retarded and erratic gross motor development on a single
      exam. Twelve offspring of hospitalized schizophrenic mothers and 12 infants in a
      "Well Baby Clinic," were examined 10 times between birth and 2 years of age.
      Psychiatric interviews and psychological testing were done at 10, 15, and 22
      years of age, plus follow-up at 27-35 years of age. RESULTS: Six infants had PDM
      at 2, 6, or 13 months of age. Five individuals have been blindly diagnosed (by
      KSK) as having lifetime SZSD; all 5 had PDM before 8 months. Chi-square one
      tailed tests confirmed the predictions: (1) PDM was related to subsequent SZSD
      (chi(2) = 11.43; p < 0.0005); (2) schizophrenic mothers had more infants with PDM
      than nonschizophrenic mothers (chi(2) = 3.28; p < 0.05); and (3) schizophrenic
      mothers had more SZSD offspring than nonschizophrenic mothers (chi(2) = 6.39; p <
      0.0125). DISCUSSION: These first behavioral observations of aberrant
      neurodevelopment in pre- SZSD infants support the evidence of early
      neurodevelopmental disorder seen in studies of brain pathology in SZSD adults.

PMID- 16092904
TI  - Longitudinal course of schizophrenia spectrum symptoms in offspring of
      psychiatrically hospitalized mothers.
AB  - OBJECTIVE: The aim of this study was to describe schizophrenia spectrum symptoms
      (SZSD) in children and adolescents with schizotypal personality disorder (SPD) as
      adults. INTRODUCTION: There are no descriptive studies of children who develop
      into adults with SPD. METHOD: Twelve offspring of psychiatrically hospitalized
      mothers (6 mothers with schizophrenia), were compared with 11 socioeconomic
      status (SES)-matched offspring of control, non-ill mothers. Offspring were
      evaluated clinically and psychometrically between infancy and 2, 10, 15 years of
      age, and adulthood. Adult Axis I and II diagnoses were made blind to infant and
      parent status. RESULTS: Six hospitalized mothers were diagnosed with
      schizophrenia, 6 with other severe psychopathology. Offspring with SZSD more
      likely had schizophrenic mothers, and childhood deteriorating IQs, symptoms of
      social isolation, constricted affect, digressive speech, suspiciousness, and
      excessive social anxiety. Global assessment scores in SZSD offspring were lower
      in childhood and adulthood than comparison offspring. DISCUSSION: Children with
      SZSD met currently accepted criteria for schizotypy; 3 by 10 years of age, and 2
      by 19 years of age. Differential diagnosis is discussed. An appendix of case
      histories is presented.

PMID- 16092905
TI  - Development from birth to adolescence of children at-risk for schizophrenia.
AB  - OBJECTIVE: Offspring of patients with schizophrenia are at-risk for developing
      schizophrenia in adult life. The aim of this paper is to describe the development
      from infancy through adolescence of a sample of Israeli young people at-risk for
      schizophrenia. METHODS: The Jerusalem Infant Development Study (JIDS) has
      followed prospectively from birth through adolescence 15 young people who have a
      parent with schizophrenia. Neurobehavioral data were gathered at infancy, middle
      childhood, and adolescence. Mental disorder was assessed at adolescence. RESULTS:
      Data suggest that some children whose parents have schizophrenia are at increased
      risk for a variety of neuromotor, cognitive, and attentional problems during
      infancy and childhood, compared to children whose parents had no mental disorder
      or nonschizophrenia mental disorder. Those high-risk children with
      neurobehavioral signs are also more likely to have poorer social adjustment,
      greater social withdrawal, and more symptoms within the schizophrenia spectrum.
      Case studies are presented of two children with early neurobehavioral impairment
      who, as adolescents, developed disorders within the schizophrenia spectrum.
      CONCLUSION: Because neurobehavioral impairment may be marking genetic
      vulnerability to schizophrenia spectrum disorders, clinicians treating children
      whose parents have schizophrenia need to thoroughly evaluate symptoms of mental
      disorder--but also neuromotor and neuropsychological functioning.

PMID- 16092906
TI  - Childhood-onset schizotypal disorder: a follow-up study and comparison with
      childhood-onset schizophrenia.
AB  - OBJECTIVE: This paper presents results from the UCLA Follow-Up Study of Childhood
      Onset Schizophrenia (SZ) Spectrum Disorders. METHOD: We assessed 12 children with
      schizotypal personality disorder (SPD) and 18 children with schizophrenia 1-7
      years following initial project intake. RESULTS: There was significant continuity
      between SZ spectrum disorders in childhood and adolescence. Although not all
      children who presented initially with SZ spectrum disorders continued to meet
      criteria for SZ spectrum disorder as they progressed through the follow-up
      period, rates of SZ spectrum disorders ranged from 75% to 92% across the 3 follow
      up years for children initially presenting with SPD, and from 78% to 89% for
      children initially presenting with SZ. CONCLUSION: The most common clinical
      outcome for children with SPD was continuing SPD, supporting the hypothesis of
      continuity between childhood and later SPD. However, 25% of the SPD sample
      developed more severe SZ spectrum disorders (schizophrenia or schizoaffective
      disorder), also supporting the hypothesis that SPD represents a risk or precursor
      state for more severe SZ spectrum disorders.

PMID- 16092907
TI  - Searching for the liability to schizophrenia: concepts and methods underlying
      genetic high-risk studies of adolescents.
AB  - Conceptualizations of the liability for schizophrenia help guide the development
      of research protocols, which, in turn, provide empirical confirmations or
      disconfirmations of the conceptualization's tenets. This paper focuses on a
      conception of liability and its relationships to genetic adolescent high-risk
      studies. Specifically, the derivation and nature of a proposed multidimensional
      syndrome of liability to schizophrenia ("schizotaxia") are outlined, followed by
      a representative review of features reported in previous high-risk studies that
      may be related to schizotaxia, and a perspective on future high-risk
      investigations. Overall, genetic high-risk studies generally confirm the concept
      of liability in the offspring of parents with schizophrenia, as expressed by
      deficits or abnormalities in multiple dimensions. It is concluded that high-risk
      studies on the liability to schizophrenia provide an important tool with which to
      explore the etiology and development of schizophrenia, in part by contributing to
      the identification and validation of specific liability syndromes.

PMID- 16092908
TI  - Prospective study of adolescents with subsyndromal psychosis: characteristics and
      outcome.
AB  - OBJECTIVE: The aim of this study was to examine the characteristics and outcome
      of adolescents with psychotic disorder not otherwise specified (PsyNOS) and brief
      psychotic disorder (BrPsy), two neglected subsyndromal diagnostic entities.
      METHODS: As part of an ongoing, naturalistic study investigating adolescents
      considered to be prodromal for schizophrenia, 29 youngsters (mean age, 16.2 +/-
      2.7 years) with PsyNOS or BrPsy were identified as theoretically at highest risk
      for schizophrenia and followed for over 6 (mean, 22.8 +/- 19.4) months. RESULTS:
      Contrary to our expectations, only 7 of the 26 individuals (27.0%) with follow-up
      data developed schizophrenia or schizoaffective disorder, and only 2 subjects
      (7.7%) retained their diagnosis of BrPsy/PsyNOS. The most frequent other
      diagnoses at follow-up were mood disorders (34.6%), personality disorders
      (11.5%), and obsessive-compulsive disorder (7.7%). Regarding severity of outcome,
      38.5% of the patients progressed to a syndromal psychotic disorder, 23.1%
      continued to have attenuated positive symptoms, and 38.4% improved to having
      attenuated negative symptoms only, or no positive or negative symptoms. BrPsy was
      associated with lower maximum levels of negative symptoms (p = 0.02) and higher
      likelihood of symptom remission (p = 0.02). CONCLUSIONS: This study indicates
      that psychotic symptoms not fulfilling criteria for schizophrenia or a psychotic
      mood disorder are unreliable predictors of a syndromal psychotic disorder outcome
      at 2 years. Long-term studies of PsyNOS and BrPsy are needed to clarify where
      these disorders fall in the developmental course of schizophrenia.

PMID- 16092909
TI  - The psychosis prodrome in adolescent patients viewed through the lens of DSM-IV.
AB  - OBJECTIVE: Recently developed research criteria have made it possible to identify
      adolescents at imminent risk for psychosis. However, the array of symptomatology
      in these patients is broad and has not yet been systematically characterized
      using established diagnostic and assessment tools. METHOD: The authors
      characterized 24 adolescent research participants at the UCLA Center for the
      Assessment and Prevention of Prodromal States (CAPPS) using structured interviews
      for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, (DSM
      IV), the Child Behavior Checklist (CBCL), and information regarding psychiatric
      treatment histories. Two composite cases are also presented. RESULTS: The most
      common DSM-IV diagnosis at study entry was major depression, followed by anxiety
      disorder not otherwise specified (NOS), and social phobia. Most participants met
      criteria for at least one subthreshold condition, including obsessive-compulsive
      disorder (OCD), psychosis, mania or hypomania, and generalized anxiety. CBCL data
      revealed high rates of affective disturbance and broad-ranging symptomatology, as
      did participants' diagnostic and treatment histories. CONCLUSIONS: Consistent
      with retrospective studies of patients with first-episode psychosis, findings
      revealed frequent mood and anxiety disturbance during the prodromal phase of
      illness. The DSM-IV does not offer a clear framework for describing the
      widespread subthreshold symptomatology that characterizes putatively prodromal
      patients. The authors consider whether the psychosis prodrome merits designation
      as a recognized clinical entity.

PMID- 16092910
TI  - Autism spectrum traits in children with mood and anxiety disorders.
AB  - The autism spectrum disorders (ASDs) can present with symptoms commonly found in
      mood and anxiety disorders. The Social Communication Questionnaire (SCQ),
      Children's Communication Checklist (CCC-2), and the Social Reciprocity Scale
      (SRS) were used to screen children in a mood disorders research clinic setting
      for symptoms of ASD. Ninety-three patients (mean age, 12.7 +/- 2.8 years; percent
      male, 63%) completed at least one scale, and 50 children completed all three. The
      prevalence of those screening positive for a possible ASD on one instrument was
      62% and on all three measures was 8%. Fifty-seven percent (n = 21/37; odds ratio,
      4.59 [95% confidence interval (CI) = 1.40-15.11]) of those scoring in the "ASD
      likely" range on the SRS scored in that range on the CCC-2. Only 16% (n = 6/37;
      odds ratio, not significant (NS)) of those scoring in the ASD-likely range on the
      SRS, and 14% (n = 5/37; odds ratio, NS) of those scoring in the ASD-likely range
      on the CCC-2, scored similarly on the SCQ. These results demonstrate a need to
      develop valid and reliable instruments to screen for ASDs in children presenting
      outside of ASD clinics.

PMID- 16092911
TI  - A controlled study of formal thought disorder in children with autism and
      multiple complex developmental disorders.
AB  - Along with well-defined categories in classification systems (e.g., autistic
      disorders and attention-deficit/hyperactivity disorder (ADHD)), practitioners are
      confronted with many children showing mixed forms of developmental
      psychopathology. These clusters of symptoms are on the borderlines of more
      defined categories. The late Donald Cohen proposed heuristic criteria to study a
      group defined by impaired social sensitivity, impaired regulation of affect, and
      thinking disorders under the name multiple complex developmental disorders
      (MCDD). Although these children meet criteria for pervasive developmental
      disorder--not otherwise specified (PDD-NOS), they have additional important
      clinical features, such as thought disorder. After highlighting similarities and
      differences between MCDD and comparable groups (e.g., multidimensionally impaired
      children), this paper presents the findings of a study comparing formal thought
      disorder scores in children with MCDD to children with autism spectrum diagnoses,
      such as autistic disorder (AD), and to children with nonspectrum diagnoses, such
      as ADHD and anxiety disorders. METHODS: Videotaped speech samples of four groups
      of high-functioning, latency-aged children with MCDD, AD, ADHD, and anxiety
      disorders were compared to a control group of normal children using the Kiddie
      Formal Thought Disorder Rating Scale (K-FTDS). RESULTS: High formal thought
      disorder scores were found both in the AD and MCDD groups, low rates in the ADHD
      groups, and no thought disorder in the anxiety disorder and normal control
      groups. The severity of formal thought disorder was related to verbal IQ scores
      within the AD and MCDD groups. CONCLUSION: High formal thought scores in children
      with complex developmental disorders, such as AD and MCDD, appear to reflect
      impaired communication skills rather than early signs of psychosis.

PMID- 16092912
TI  - The presentation of anxiety in children with pervasive developmental disorders.
AB  - OBJECTIVE: Although the Diagnostic and Statistical Manual of Mental Disorders,
      4th ed. (DSM-IV) diagnostic criteria generally discourage the diagnosis of other
      Axis I disorders in children with pervasive developmental disorder (PDD), anxiety
      symptoms are often observed in this clinical population. Moreover, there are some
      albeit limited data that suggest an association between anxiety and psychotic
      symptoms in children. Because co-occurring psychiatric symptoms have important
      clinical implications, this study examined anxiety and psychotic symptoms in
      children with and without PDD. METHOD: Parents and teachers completed the Early
      Childhood Inventory-4 (ECI-4) or the Child Symptom Inventory (CSI-4) for children
      evaluated in a developmental disabilities clinic (PDD) or a child psychiatry
      outpatient clinic (non-PDD). Children were divided into four groups: 3-5- year
      olds with (n = 182) and without (n = 135) PDD, and 6-12-year-olds with (n = 301)
      and without (n = 191) PDD. The 6-12-year-olds were further divided into high
      anxious and low-anxious subgroups based on CSI-4 ratings and compared with regard
      to severity of psychotic symptoms. RESULTS: Teachers rated preschoolers with PDD
      as exhibiting more severe anxiety symptoms than the non-PDD group; however, the
      converse was true for parent ratings. For 6-12- year-olds, both parents and
      teachers rated children with PDD as significantly more anxious than non-PDD
      clinic referrals. In general, the severity of anxiety symptoms varied by PDD
      subtype (Asperger's disorder > PDDNOS > Autistic disorder) and IQ (high > low).
      Furthermore, highly anxious 6-12-year-olds with PDD received significantly higher
      parent and teacher ratings of psychotic symptom severity (strange behaviors,
      hearing voices, illogical thinking, inappropriate affect, and odd thoughts) than
      our low-anxious group, even when controlling for PDD symptom severity. Moreover,
      the relation between anxiety level and psychotic symptom severity was similar for
      both PDD and non-PDD children. Parent and teachers differed in their perceptions
      of the severity of specific anxiety symptoms. In addition, parent- versus teacher
      defined anxiety level groups varied with regard to the differential severity of
      psychotic symptoms. This finding highlights the importance of continued
      investigation of source-specific syndromes in children with PDD. Two case
      vignettes are presented. CONCLUSION: Anxiety appears to be a clinically important
      concern in many children with PDD. Similarities in anxiety symptom presentation
      and their association with psychotic symptoms in both children with and without
      PDD support the possibility of: (1) psychiatric comorbidity in the former; (2) at
      least some overlap in causal mechanisms for anxiety and psychotic symptoms in
      both PDD and non-PDD children; and (3) a unique diagnostic entity comprised of
      PDD, anxiety, and psychotic symptoms. Lastly, clinicians should seriously
      consider dual diagnoses in children with PDD.

PMID- 16092913
TI  - Phenomenology and diagnostic stability of youths with atypical psychotic
      symptoms.
AB  - OBJECTIVE: This study aimed to better characterize the phenomenology and
      diagnostic stability of youths that report atypical psychotic symptoms. METHOD:
      In a 2-year longitudinal follow-up study, youths reporting atypical psychotic
      symptoms (n = 20) were compared with youths with schizophrenia (n = 27) and
      youths with bipolar disorder with psychotic features (n = 22) on psychotic,
      dissociative, and general symptomatology, comorbid diagnoses, previous abuse, and
      overall functioning. Diagnoses were obtained using structured diagnostic
      interviews (i.e., the Structured Clinical Interview for DSM-IV and the Diagnostic
      Interview for Children and Adolescents). RESULTS: None of the subjects reporting
      atypical psychotic symptoms went on to develop a classic psychotic illness by the
      year 2 follow-up. These subjects had significantly higher rates of abuse and
      dissociative symptoms, and were significantly more likely to receive a diagnosis
      of posttraumatic stress disorder (PTSD) or a depressive disorder than youths with
      schizophrenia or bipolar disorder. CONCLUSION: Our findings suggest that youths
      with atypical, fleeting, or situationally specific hallucinations are more likely
      to have a mood or anxiety disorder (such as PTSD) than a current or prodromal
      psychotic illness.

PMID- 16092914
TI  - Multidimensionally impaired: the good news.
AB  - INTRODUCTION: Long-term outcomes in children with atypical psychosis have been
      poorly studied. Four to 6 weeks of inpatient observation and up to 11 years
      (mean, 4.0 +/- 1.3 years) of follow- up have afforded us some experience with
      this probably heterogeneous group of transiently psychotic patients commonly
      mislabeled as schizophrenic. Despite severe preadmission morbidity, some patients
      have successfully remained neuroleptic-free since discharge. Predictors of good
      versus poor outcome were sought. METHODS: Of roughly 150 patients admitted with
      the presumptive diagnosis of schizophrenia, 32 patients were discharged meeting
      criteria for psychosis not otherwise specified (NOS), otherwise labeled by the
      NIMH team as "multidimensionally impaired" (MDI). Admission and biannual follow
      up data included a semistructured clinical interview with the Schedule for
      Affective Disorders and Schizophrenia for School Age Children (K-SADS), IQ
      testing, clinical rating scales (e.g., Clinical Global Impression Scale (CGI),
      Children's Global Assessment Scale (C-GAS), Brief Psychiatric Rating Scale
      (BPRS), Scales for the Assessment Negative and Positive Symptoms (SANS and SAPS),
      and Bunney-Hamburg (B-H)). At follow-up (as of February 2005) 38% of patients (12
      of 32) met criteria for bipolar 1 disorder, 12% (4 of 23) for major depressive
      disorder (MDD), and 3% (1 of 32) for schizoaffective disorder. The remaining 47%
      of patients (15 of 32) were divided into two groups on the basis of whether they
      were in remission and neuroleptic-free ("good outcome," n = 5) or still severely
      impaired and/or psychotic regardless of pharmacotherapy ("poor outcome," n = 10)
      at follow-up. RESULTS: Good-outcome patients had a significantly higher baseline
      level of functioning (on admission and on medications). This was demonstrated by
      better scores on CGI (3.5 +/- 0.6 versus 4.8 +/- 0.8; p = 0.03) and C-GAS (66.3
      +/- 6.3 versus 38.6 +/- 11.5; p = 0.01). Groups were otherwise comparable in
      demographic data (gender, race, socioeconomic status, age at onset), months of
      neuroleptic exposure, severity of psychotic symptoms, and level of premorbid
      functioning. CONCLUSION: C-GAS (which correctly classified 85.7% of good-outcome
      subjects) and CGI at baseline appear to predict outcome. On other variables, MDI
      subgroups were remarkably similar.

PMID- 16092915
TI  - Risperidone-induced psychosis and depression in a child with a mitochondrial
      disorder.
AB  - OBJECTIVE: To our knowledge, this is the first published case report of an
      adolescent girl with a mitochondrial disorder and depression who displayed both
      new-onset psychotic and increased mood symptoms during treatment with
      risperidone. DATA: A 16-year-old girl was treated with risperidone for mood
      lability and impulsivity at a community hospital. Within days, she developed
      paranoid ideation, profound psychomotor retardation, increased depression, and
      fatigue. She was transferred to an inpatient psychiatric hospital, where she was
      taken off risperidone. Within 48 hours after discontinuation of the medication,
      she had complete resolution of psychotic symptoms, fatigue, and psychomotor
      retardation, and her depression improved. CONCLUSIONS: This observation of "on
      off" risperidone treatment suggests that risperidone may have worsened both
      psychiatric and physical manifestations of the mitochondrial disorder in this
      adolescent. These findings are consistent with recent in vitro literature, which
      implicate a series of neuroleptic medications with mitochondrial dysfunction.
      Furthermore, the authors provide diagnostic and treatment options that are
      available for mitochondrial disorders, which are of interest to child
      psychiatrists due to the central nervous system manifestations of these
      disorders.

PMID- 16092917
TI  - Quantification of fluorescence in thick specimens, with an application to cyclin
      B-GFP expression in starfish oocytes.
AB  - BACKGROUND INFORMATION: Fluorescence imaging of living cells is widely used in
      cell biology. It is now being extended to thick specimens such as large cells or
      tissues where it is important to establish methods for obtaining quantitative
      fluorescence data due to the increasing importance of computational and systems
      biology approaches. RESULTS: Fluorescent solutions were used as a calibration
      standard for determining cellular fluorescence concentrations from z series image
      sequences. The accuracy of the measurements was evaluated using quantitatively
      injected cells. Different fluorescence attenuation rates of the cytoplasm and
      nucleoplasm were documented, and autofluorescence levels were determined. This
      method was used to characterize the effect of cyclin B overexpression on cell
      cycle timing in starfish oocytes. The time interval between application of
      maturation hormone and germinal vesicle breakdown decreased with increasing
      cyclin B-GFP (green fluorescent protein) concentration to a level of 100-300 nM,
      beyond which there was no effect. CONCLUSIONS: Conditions for determining
      fluorescent probe concentrations in large cells or multicellular tissues were
      established, which will facilitate the collection of data for quantitative
      studies. This method was used to characterize the effect of cyclin B-GFP
      expression levels on cell-cycle timing in starfish oocytes.

PMID- 16092918
TI  - Inhibition of transferrin receptor 1 transcription by a cell density response
      element.
AB  - TfR1 (transferrin receptor 1) mediates the uptake of transferrin-bound iron and
      thereby plays a critical role in cellular iron metabolism. Its expression is
      coupled to cell proliferation/differentiation and controlled in response to iron
      levels and other signals by transcriptional and post-transcriptional mechanisms.
      It is well established that TfR1 levels decline when cultured cells reach a high
      density and in the present study we have investigated the underlying mechanisms.
      Consistent with previous findings, we demonstrate that TfR1 expression is
      attenuated in a cell-density-dependent manner in human lung cancer H1299 cells
      and in murine B6 fibroblasts as the result of a marked decrease in mRNA content.
      This response is not associated with alterations in the RNA-binding activity of
      iron regulatory proteins that are indicative of a transcriptional mechanism.
      Reporter assays reveal that the human TfR1 promoters contains sequences mediating
      cell-density-dependent transcriptional inhibition. Mapping of the human and mouse
      TfR1 promoters identified a conserved hexa-nucleotide 5'-GAGGGC-3' motif with
      notable sequence similarity to a previously described element within the IGF-2
      (insulin-like growth factor-2) promoter. We show that this motif is necessary for
      the formation of specific complexes with nuclear extracts and for cell-density
      dependent regulation in reporter gene assays. Thus the TfR1 promoter contains a
      functional 'cell density response element' (CDRE).

PMID- 16092919
TI  - Tetravalent single-chain avidin: from subunits to protein domains via circularly
      permuted avidins.
AB  - scAvd (single-chain avidin, where two dcAvd are joined in a single polypeptide
      chain), having four biotin-binding domains, was constructed by fusion of
      topologically modified avidin units. scAvd showed similar biotin binding and
      thermal stability properties as chicken avidin. The DNA construct encoding scAvd
      contains four circularly permuted avidin domains, plus short linkers connecting
      the four domains into a single polypeptide chain. In contrast with wild-type
      avidin, which contains four identical avidin monomers, scAvd enables each one of
      the four avidin domains to be independently modified by protein engineering.
      Therefore the scAvd scaffold can be used to construct spatially and
      stoichiometrically defined pseudotetrameric avidin molecules showing different
      domain characteristics. In addition, unmodified scAvd could be used as a fusion
      partner, since it provides a unique non-oligomeric structure, which is fully
      functional with four high-affinity biotin-binding sites. Furthermore, the subunit
      to-domain strategy described in the present study could be applied to other
      proteins and protein complexes, facilitating the development of sophisticated
      protein tools for applications in nanotechnology and life sciences.

PMID- 16092920
TI  - Deciphering the molecular bases of Mycobacterium tuberculosis binding to the
      lectin DC-SIGN reveals an underestimated complexity.
AB  - Interactions between dendritic cells and Mycobacterium tuberculosis, the
      aetiological agent of tuberculosis in humans, are thought to be central to anti
      mycobacterial immunity. We have previously shown that M. tuberculosis binds to
      human monocyte-derived dendritic cells mostly through the C-type lectin DC-SIGN
      (dendritic-cell-specific intercellular molecule-3-grabbing non-integrin)/CD209,
      and we have suggested that DC-SIGN may discriminate between mycobacterial species
      through recognition of the mannose-capping residues on the lipoglycan
      lipoarabinomannan of the bacterial envelope. Here, using a variety of fast- and
      slow-growing Mycobacterium species, we provide further evidence that mycobacteria
      recognition by DC-SIGN may be restricted to species of the M. tuberculosis
      complex. Fine analyses of the lipoarabinomannan molecules purified from these
      species show that the structure and amount of these molecules alone cannot
      account for such a preferential recognition. We propose that M. tuberculosis
      recognition by DC-SIGN relies on both a potential difference of accessibility of
      lipoarabinomannan in its envelope and, more probably, on the binding of
      additional ligands, possibly including lipomannan, mannose-capped arabinomannan,
      as well as the mannosylated 19 kDa and 45 kDa [Apa (alanine/proline-rich
      antigen)] glycoproteins. Altogether, our results reveal that the molecular basis
      of M. tuberculosis binding to DC-SIGN is more complicated than previously thought
      and provides further insight into the mechanisms of M. tuberculosis recognition
      by the immune system.

PMID- 16092921
TI  - Whole influenza virus vaccine is more immunogenic than split influenza virus
      vaccine and induces primarily an IgG2a response in BALB/c mice.
AB  - The aim of this study was to compare the kinetics and the magnitude of the
      humoral immune response to two different influenza vaccine formulations, whole
      and split virus vaccines. BALB/c mice were immunized intramuscularly with one or
      two doses (3 weeks apart) of 7.5, 15 or 30 microg of haemagglutinin of monovalent
      A/Panama/2007/99 (H3N2) split or whole virus vaccine. The two vaccine
      formulations induced similar kinetics of the antibody-secreting cells response;
      however, differences in the magnitude were observed in the spleen and bone
      marrow. Vaccination with whole virus vaccine generally elicited a quicker and
      higher neutralizing antibody response, particularly after the first dose of
      vaccine. The two vaccine formulations gave different immunoglobulin G (IgG)
      subclass profiles. Split virus vaccine stimulated both IgG1 and IgG2a antibodies
      suggestive of mixed T-helper 1 (Th1) and Th2 response, whereas whole virus
      vaccine induced mainly an IgG2a antibody response, which is indicative of a
      dominant Th1 response. The increased immunogenicity of whole virus vaccine in a
      naive population could reduce the vaccine concentration needed to provide
      protective immunity.

PMID- 16092922
TI  - Morphological characterization of receptor activator of NFkappaB ligand (RANKL)
      and IL-1beta expression in rodent collagen-induced arthritis.
AB  - Bone loss represents a major unsolved problem in rheumatoid arthritis (RA). The
      receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for the
      development and activation of osteoclasts, which are key mediators of bone
      erosions. This study was performed to determine temporal and spatial expression
      of RANKL compared with the potentially destructive cytokine interleukin-1beta (IL
      1beta), related to progression of synovitis and joint destruction in collagen
      induced arthritis (CIA), a model of RA. CIA was induced in dark agouti (DA) rats,
      and tissue specimens were obtained for immunohistochemical analyses at various
      time points before and after disease onset. Arthritis was monitored visually, and
      joint pathology was examined histologically. No disease-preceding expression of
      RANKL was detected. However, a marked increase of both RANKL- and IL-1beta
      expressing cells correlated with the progression of synovial inflammation and
      clinical disease severity. Abundant and concomitant expression of these cytokines
      was detected at sites of bone erosion, where a colocalization by osteoclast-like
      multinuclear tartrate-resistant acid phosphatase (TRAP)+ cells was noted. In
      contrast to the paucity of RANKL expression in cartilage, an abundant expression
      of IL-1beta was demonstrated, particularly in superficial cartilage layers. These
      data support the hypothesis that RANKL and IL-1beta are central contributors to
      joint destruction in CIA.

PMID- 16092924
TI  - High functional levels of thrombin-activatable fibrinolysis inhibitor are
      associated with an increased risk of first ischemic stroke.
AB  - BACKGROUND AND OBJECTIVE: Several studies have suggested that thrombin
      activatable fibrinolysis inhibitor (TAFI) levels are associated with the risk of
      arterial thrombosis, but results have been contradictory. We studied functional
      TAFI levels and TAFI gene polymorphisms in 124 patients with a recent ischemic
      stroke and 125 age- and sex-matched controls to establish the role of TAFI in
      ischemic stroke. METHODS AND RESULTS: Functional TAFI levels, defined as TAFI
      related retardation (RT), the difference in clot lysis time (LT) in the absence
      or presence of a specific activated TAFI inhibitor (potato carboxypeptidase
      inhibitor [PCI]), were higher in patients than controls (19.5 +/- 4.2 vs. 17.7 +/
      3.7 min, P < 0.005). Clot LTs in the presence of PCI, which were independent of
      TAFI, were also increased in ischemic stroke patients. This indicates that in
      these patients fibrinolysis is impaired not only by high TAFI levels, but also by
      other mechanisms. Individuals with functional TAFI levels in the highest quartile
      had an increased risk of ischemic stroke compared with the lowest quartile [odds
      ratio (OR) 4.0, 95% confidence interval (CI): 1.6-9.8]. In an unselected group of
      36 of the 125 stroke patients functional TAFI levels were also measured at 3
      months, and were persistently high. This indicates that increased functional TAFI
      levels after stroke are not caused by an acute phase reaction. No difference was
      found between patients and controls with respect to TAFI genotype distribution.
      CONCLUSIONS: Increased functional TAFI levels, resulting in decreased
      fibrinolysis, are associated with an increased risk of ischemic stroke.

PMID- 16092928
TI  - Adenosine A2A receptor stimulation potentiates nitric oxide release by activated
      microglia.
AB  - The absence of adenosine A2A receptors, or its pharmacological inhibition, has
      neuroprotective effects. Experimental data suggest that glial A2A receptors
      participate in neurodegeneration induced by A2A receptor stimulation. In this
      study we have investigated the effects of A2A receptor stimulation on control and
      activated glial cells. Mouse cortical mixed glial cultures (75% astrocytes, 25%
      microglia) were treated with the A2A receptor agonist CGS21680 alone or in
      combination with lipopolysaccharide (LPS). CGS21680 potentiated
      lipopolysaccharide-induced NO release and NO synthase-II expression in a time-
      and concentration-dependent manner. CGS21680 potentiation of lipopolysaccharide
      induced NO release was suppressed by the A2A receptor antagonist ZM-241385 and
      did not occur on mixed glial cultures from A2A receptor-deficient mice. In mixed
      glial cultures treated with LPS + CGS21680, the NO synthase-II inhibitor 1400W
      abolished NO production, and NO synthase-II immunoreactivity was observed only in
      microglia. Binding experiments demonstrated the presence of A2A receptors on
      microglial but not on astroglial cultures. However, the presence of astrocytes
      was necessary for CGS21680 potentiating effect. In light of the reported
      neurotoxicity of microglial NO synthase-II and the neuroprotection of A2A
      receptor inhibition, these data suggest that attenuation of microglial NO
      production could contribute to the neuroprotection afforded by A2A receptor
      antagonists.

PMID- 16092929
TI  - JNK inhibitory kinase is up-regulated in retinal ganglion cells after axotomy and
      enhances BimEL expression level in neuronal cells.
AB  - Optic nerve transection results in retinal ganglion cell (RGC) death in adult
      mammals, after the alteration of gene expression of RGCs. To elucidate the
      molecular mechanism by which axotomy induces RGC death, we isolated the molecules
      up-regulated after optic nerve transection. One of these, axotomy-related
      [corrected] gene (ARG)357, an 898-amino-acid [corrected] protein containing a
      complete serine-threonine kinase domain, was isolated from a subtraction library
      of the rat retina. The sequence showed that this gene was a rat homolog of human
      c-Jun N-terminal kinase (JNK) inhibitory kinase and so belonged to the germinal
      center kinase-VIII subfamily of Sterile20s protein kinase. We designated ARG357
      as rat JNK inhibitory kinase (JIK). Rat JIK was expressed ubiquitously in various
      tissues and was highly expressed in the retina, with selective expression in
      RGCs. After axotomy, BimEL and Hrk, which are BH3-only proteins, and rat JIK were
      up-regulated in RGCs. Overexpression of rat JIK in neuronal cells up-regulated
      the expression of BimEL, but not that of Hrk. These results indicate that JIK may
      contribute to axotomy-induced RGC death by up-regulating the expression of BH3
      only protein.

PMID- 16092930
TI  - Increased nuclear factor-erythroid 2 p45-related factor 2 activity protects SH
      SY5Y cells against oxidative damage.
AB  - The ability of cells to control the balance between the generation and quenching
      of reactive oxygen species is important in combating potentially damaging effects
      of oxidative stress. One mechanism that cells use to maintain redox homeostasis
      is the antioxidant response pathway. Antioxidant response elements (AREs) are cis
      acting elements located in regulatory regions of antioxidant and phase II
      detoxification genes. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is a
      member of the Cap 'n' Collar family of transcription factors that binds to the
      ARE and regulates the transcription of specific ARE-containing genes such as
      NAD(P)H:quinone oxidoreductase 1, glutamylcysteine synthetase and heme oxygenase.
      Activation of Nrf2 results in release from its negative repressor, Kelch-like ECH
      associated protein 1 (Keap1), and allows Nrf2 to translocate into the nucleus to
      induce gene expression. In this study, we demonstrate that increasing Nrf2
      activity by various methods, including chemical induction, Nrf2 overexpression or
      Keap1 siRNA knockdown, protects cells against specific types of oxidative damage.
      Cells were protected against 6-hydroxydopamine- and 3-morpholinosydnonimine
      mediated toxicity but not against 1-methyl-1-4-phenylpyridinium toxicity. As
      oxidative stress is a hallmark of several neurodegenerative disorders, including
      Parkinson's disease, pharmacological agents that selectively target the Keap1
      Nrf2 pathway may provide a novel neuroprotective strategy for the treatment of
      these diseases.

PMID- 16092933
TI  - Metabolic correction in microglia derived from Sandhoff disease model mice.
AB  - Sandhoff disease is an autosomal recessive lysosomal storage disease caused by a
      defect of the beta-subunit gene (HEXB) associated with simultaneous deficiencies
      of beta-hexosaminidase A (HexA; alphabeta) and B (HexB; betabeta), and excessive
      accumulation of GM2 ganglioside (GM2) and oligosaccharides with N
      acetylglucosamine (GlcNAc) residues at their non-reducing termini. Recent studies
      have shown the involvement of microglial activation in neuroinflammation and
      neurodegeneration of this disease. We isolated primary microglial cells from the
      neonatal brains of Sandhoff disease model mice (SD mice) produced by disruption
      of the murine Hex beta-subunit gene allele (Hexb-/-). The cells expressed
      microglial cell-specific ionized calcium binding adaptor molecule 1 (Iba1)
      immunoreactivity (IR) and antigen recognized by Ricinus communis agglutinin
      lectin-120 (RCA120), but not glial fibrillary acidic protein (GFAP)-IR specific
      for astrocytes. They also demonstrated significant intracellular accumulation of
      GM2 and GlcNAc-oligosaccharides. We produced a lentiviral vector encoding for the
      murine Hex beta-subunit and transduced it into the microglia from SD mice with
      the recombinant lentivirus, causing elimination of the intracellularly
      accumulated GM2 and GlcNAc-oligosaccharides and secretion of Hex isozyme
      activities from the transduced SD microglial cells. Recomibinant HexA isozyme
      isolated from the conditioned medium of a Chinese hamster ovary (CHO) cell line
      simultaneously expressing the human HEXA (alpha-subunit) and HEXB genes was also
      found to be incorporated into the SD microglia via cell surface cation
      independent mannose 6-phosphate receptor and mannose receptor to degrade the
      intracellularly accumulated GM2 and GlcNAc-oligosaccharides. These results
      suggest the therapeutic potential of recombinant lentivirus encoding the murine
      Hex beta-subunit and the human HexA isozyme (alphabeta heterodimer) for metabolic
      cross-correction in microglial cells involved in progressive neurodegeneration in
      SD mice.

PMID- 16092934
TI  - Roles of transmembrane domain 2 and the first intracellular loop in human
      noradrenaline transporter function: pharmacological and SCAM analysis.
AB  - The aim was to investigate the roles of transmembrane domain 2 and the adjacent
      region of the first intracellular loop in determining human noradrenaline
      transporter (hNET) function by pharmacological and substituted-cysteine
      accessibility method (SCAM) analyses. It was first necessary to establish a
      suitable background NET for SCAM. Alanine mutants of endogenous hNET cysteines,
      hC86A, hC131A and hC339A, were examined and showed no marked effects on
      expression or function. hNET and the mutants were also resistant to
      methanethiosulfonate (MTS), ethylammonium (MTSEA) and MTStrimethylammonium
      (MTSET). Hence, wild-type hNET is an appropriate background for production of
      cysteine mutants for SCAM. Pharmacological investigation showed that all mutants
      except hT99C and hL109C showed reduced cell-surface expression, while all except
      hM107C showed a reduction in functional activity. The mutations did not markedly
      affect the apparent affinities of substrates, but apparent affinities of cocaine
      were decreased 7-fold for hP97C and 10-fold for hF101C and increased 12-fold for
      hY98C. [3H]Nisoxetine binding affinities were decreased 13-fold for hP97C and 5
      fold for hF101C. SCAM analysis revealed that only hL102C was sensitive to 1.25 mm
      MTSEA, and this sensitivity was protected by noradrenaline, nisoxetine and
      cocaine. The results suggest that this region of hNET is important for
      interactions with antidepressants and cocaine, but it is probably not involved in
      substrate translocation mechanisms.

PMID- 16092935
TI  - Why do Nogo/Nogo-66 receptor gene knockouts result in inferior regeneration
      compared to treatment with neutralizing agents?
AB  - IN-1, the monoclonal antibody against the exon 3-encoded N-terminal domain of
      Nogo-A, and the Nogo-66 receptor (NgR) antagonist NEP1-40 have both shown
      efficacy in promoting regeneration in animal spinal cord injury models, the
      latter even when administered subcutaneously 1 week after injury. These results
      are supportive of the hypothesis that the Nogo-NgR axis is a major path for
      inhibition of spinal cord axonal regeneration and uphold the promises of these
      neutralizing agents in clinical applications. However, mice with targeted
      disruption of Nogo and NgR have, surprisingly, only modest regenerative capacity
      (if any) compared with treatment with IN-1 or NEP1-40. Disruption of the Nogo
      gene by various groups yielded results ranging from significant regenerative
      improvement in young mice to no improvement. Likewise, knockout of NgR produced
      some improvement in raphespinal and rubrospinal axonal regeneration, but not that
      of corticospinal neurons. Other than invoking possible differences in genetic
      background, we suggest here some possible and testable explanations for the above
      phenomena. These possibilities include effects of IN-1 and NEP1-40 on the CNS
      beyond neutralization of Nogo and NgR functions, and the latter's possible role
      in the CNS beyond that of neuronal growth inhibition.

PMID- 16092936
TI  - Serotonin 5-HT receptor blockade enhances Ca(2+)/calmodulin-dependent protein
      kinase II function and membrane expression of AMPA receptor subunits in the rat
      hippocampus: implications for memory formation.
AB  - Stimulation of hippocampal 5-HT(1A) receptors impairs memory retention. The
      highly selective 5-HT(1A) antagonist, WAY-100635, prevents the cognitive deficits
      induced not only by 5-HT(1A) stimulation but also by cholinergic or NMDA receptor
      blockade. On this basis, the effects of WAY-100635 on molecular events associated
      with memory storage were explored. In rat hippocampus, WAY-100635 produced a
      rapid increase in phosphorylated Ca(2+)/calmodulin-dependent protein kinase II
      (CaMKII) and in Ca(2+)-independent CaMKII and protein kinase A (PKA) enzyme
      activity. This increase was followed a few hours later by an enhanced membrane
      expression of AMPA receptor subunits, especially of the GluR1 subunit
      phosphorylated at the CaMKII site, pGluR1(Ser831). The same qualitative effects
      were found with the weaker 5-HT(1A) antagonist NAN-190. The effects of both
      antagonists were no longer apparent in rats with a previous 5-HT depletion
      induced by the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA),
      suggesting that 5-HT(1A) receptor blockade removes the tonic inhibition of 5-HT
      through 5-HT(1A) receptor stimulation on excitatory hippocampal neurons, with the
      consequent increase in PKA activity. In addition, administration of WAY-100635
      potentiated the learning-specific increase in the hippocampus of phospho-CaMKII,
      Ca(2+)-independent CaMKII activity, as well as the phosphorylation of either the
      CaMKII or the PKA site on the AMPA receptor GluR1 subunit. This study suggests
      that blockade of hippocampal 5-HT(1A) receptors favours molecular events
      critically involved in memory formation, and provides an in vivo molecular basis
      for the proposed utility of 5-HT(1A) receptor antagonists in the treatment of
      cognitive disorders.

PMID- 16092937
TI  - Dicer and eIF2c are enriched at postsynaptic densities in adult mouse brain and
      are modified by neuronal activity in a calpain-dependent manner.
AB  - We have hypothesized that small RNAs may participate in learning and memory
      mechanisms. Because dendritic spines are important in synaptic plasticity and
      learning, we asked whether dicer, the rate-limiting enzyme in the formation of
      small RNAs, is enriched within dendritic spines. In adult mouse brain, dicer and
      the RNA-induced silencing complex (RISC) component eIF2c were expressed in the
      somatodendritic compartment of principal neurons and some interneurons in many
      regions, and dicer was enriched in dendritic spines and postsynaptic densities
      (PSDs). A portion of dicer and eIF2c were associated with each other and with
      fragile X mental retardation protein (FMRP), as assessed by co
      immunoprecipitation. Calpain I treatment of recombinant dicer or immunopurified
      brain dicer caused a marked increase in RNAse III activity. Purified PSDs did not
      exhibit RNAse III activity, but calpain caused release of dicer from PSDs in an
      enzymatically active form, together with eIF2c. NMDA stimulation of hippocampal
      slices, or calcium treatment of synaptoneurosomes, caused a 75 kDa dicer fragment
      to appear in a calpain-dependent manner. The findings support a model whereby
      acute neuronal stimulation at excitatory synapses increases intracellular
      calcium, which activates calpain, which liberates dicer and eIF2c bound to PSDs.
      This supports the hypothesis that dicer could be involved in synaptic plasticity.

PMID- 16092938
TI  - Chronic hyperammonemia in vivo impairs long-term potentiation in hippocampus by
      altering activation of cyclic GMP-dependent-protein kinase and of
      phosphodiesterase 5.
AB  - Long-term potentiation (LTP) is impaired in the CA1 area of hippocampal slices
      from rats with chronic moderate hyperammonemia. We studied the mechanisms by
      which hyperammonemia in vivo impairs LTP. This process requires sequential
      activation of soluble guanylate cyclase, cyclic GMP-dependent protein kinase
      (PKG) and cyclic GMP-degrading phosphodiesterase. Application of the tetanus
      induced a rapid increase of cyclic GMP in slices from control or hyperammonemic
      rats, which is followed in control slices by a sustained decrease in cyclic GMP
      due to sustained activation of cyclic GMP-degrading phosphodiesterase, which in
      turn is due to sustained activation of PKG. In slices from rats with chronic
      hyperammonemia tetanus-induced decrease in cyclic GMP was delayed and transient
      due to lower and transient activation of PKG and of the phosphodiesterase.
      Hyperammonemia-induced impairment of LTP may be involved in the alterations of
      cognitive function in patients with hepatic encephalopathy.

PMID- 16092939
TI  - Structural requirements for steady-state localization of the vesicular
      acetylcholine transporter.
AB  - The vesicular acetylcholine transporter (VAChT) regulates the amount of
      acetylcholine stored in synaptic vesicles. However, the mechanisms that control
      the targeting of VAChT and other synaptic vesicle proteins are still poorly
      comprehended. These processes are likely to depend, at least partially, on
      structural determinants present in the primary sequence of the protein. Here, we
      use site-directed mutagenesis to evaluate the contribution of the C-terminal tail
      of VAChT to the targeting of this transporter to synaptic-like microvesicles in
      cholinergic SN56 cells. We found that residues 481-490 contain the trafficking
      information necessary for VAChT localization and that within this region L485 and
      L486 are strictly necessary. Deletion and alanine-scanning mutants lacking most
      of the carboxyl tail of VAChT, but containing residues 481-490, were still
      targeted to microvesicles. Moreover, we found that clathrin-mediated endocytosis
      of VAChT is required for targeting to microvesicles in SN56 and PC12 cells. The
      data provide novel information on the mechanisms and structural determinants
      necessary for VAChT localization to synaptic vesicles.

PMID- 16092940
TI  - Subcellular localization suggests novel functions for prolyl endopeptidase in
      protein secretion.
AB  - For a long time, prolyl endopeptidase (PEP) was believed to inactivate
      neuropeptides in the extracellular space. However, reports on the intracellular
      activity of PEP suggest additional, as yet unidentified, physiological functions
      for this enzyme. Here, we demonstrate using biochemical methods of subcellular
      fractionation, immunocytochemical double-labelling procedures and localization of
      PEP-enhanced green fluorescent protein fusion proteins that PEP is mainly
      localized to the perinuclear space, and is associated with the microtubulin
      cytoskeleton in human neuroblastoma and glioma cell lines. Disassembly of the
      microtubules by nocodazole treatment disrupts both the fibrillar tubulin and PEP
      labelling. Furthermore, in a two-hybrid screen, PEP was identified as binding
      partner of tubulin. These findings indicate novel functions for PEP in axonal
      transport and/or protein secretion. Indeed, a metabolic labelling approach
      revealed that both PEP inhibition and PEP antisense mRNA expression result in
      enhanced peptide/protein secretion from human U-343 glioma cells. Because
      disturbances in intracellular transport and protein secretion mechanisms are
      associated with a number of ageing-associated neurodegenerative diseases, cell
      permeable PEP inhibitors may be useful for the application in a variety of
      related clinical conditions.

PMID- 16092941
TI  - Activation of calcium-independent phospholipase A (iPLA) in brain mitochondria
      and release of apoptogenic factors by BAX and truncated BID.
AB  - Cleaved or truncated BID (tBID) is known to oligomerize both BAK and BAX.
      Previously, BAK and BAX lacing the C-terminal fragment (BAXDeltaC) were shown to
      induce modest cytochrome c (Cyt c) release from rat brain mitochondria when
      activated by tBID. We now show that tBID plus monomeric full-length BAX induce
      extensive release of Cyt c, Smac/DIABLO, and Omi/HtrA2 (but not endonuclease G
      and the apoptosis inducing factor) comparable to the release induced by
      alamethicin. This occurs independently of the permeability transition without
      overt changes in mitochondrial morphology. The mechanism of the release may
      involve formation of reactive oxygen species (ROS) and activation of calcium
      independent phospholipase A(2) (iPLA(2)). Indeed, increased ROS production and
      activated iPLA(2) were observed prior to massive Cyt c release. Furthermore, the
      extent of inhibition of Cyt c release correlated with the degree of suppression
      of iPLA(2) by the inhibitors propranolol, dibucaine, 4-bromophenacyl bromide, and
      bromenol lactone. Consistent with a requirement for iPLA(2) in Cyt c release from
      brain mitochondria, synthetic liposomes composed of lipids mimicking the outer
      mitochondrial membrane (OMM) but lacing iPLA(2) failed to release 10 kDa
      fluorescent dextran (FD-10) in response to tBID plus BAX. We propose that tBID
      plus BAX activate ROS generation, which subsequently augments iPLA(2) activity
      leading to changes in the OMM that allow translocation of certain mitochondrial
      proteins from the intermembrane space.

PMID- 16092942
TI  - Celastrol protects against MPTP- and 3-nitropropionic acid-induced neurotoxicity.
AB  - Oxidative stress and inflammation are implicated in neurodegenerative diseases
      including Parkinson's disease (PD) and Huntington's disease (HD). Celastrol is a
      potent anti-inflammatory and antioxidant compound extracted from a perennial
      creeping plant belonging to the Celastraceae family. Celastrol is known to
      prevent the production of proinflammatory cytokines, inducible nitric oxide
      synthase and lipid peroxidation. Mice were treated with celastrol before and
      after injections of MPTP, a dopaminergic neurotoxin, which produces a model of
      PD. A 48% loss of dopaminergic neurons induced by MPTP in the substantia nigra
      pars compacta was significantly attenuated by celastrol treatment. Moreover,
      celastrol treatment significantly reduced the depletion in dopamine concentration
      induced by MPTP. Similarly, celastrol significantly decreased the striatal lesion
      volume induced by 3-nitropropionic acid, a neurotoxin used to model HD in rats.
      Celastrol induced heat shock protein 70 within dopaminergic neurons and decreased
      tumor necrosis factor-alpha and nuclear factor kappa B immunostainings as well as
      astrogliosis. Celastrol is therefore a promising neuroprotective agent for the
      treatment of PD and HD.

PMID- 16092943
TI  - Biosynthesis and differential processing of two pools of amyloid-beta precursor
      protein in a physiologically inducible neuroendocrine cell.
AB  - The amyloid-beta precursor protein (APP) is linked to Alzheimer's disease through
      its pathological proteolytic processing in the secretory pathway. Nevertheless,
      surprisingly little is known about the biosynthesis of endogenous APP. We
      therefore decided to investigate the intracellular fate of newly synthesized APP
      in a physiologically inducible neuroendocrine cell, the Xenopus intermediate
      pituitary melanotrope cell. We found that the level of both APP mRNA and protein
      was about threefold induced in the activated cells of black-adapted animals.
      Intriguingly, two pools of APP were found, only one of which was up-regulated.
      This induced pool became readily N- and subsequently O-glycosylated and was
      eventually proteolytically processed by an alpha-secretase-like cleavage event
      resulting in a secreted N-terminal and a cell-associated C-terminal APP fragment.
      Conversely, only the other (non-induced, non-glycosylated and uncleaved) pool
      became phosphorylated. Thus, we report on the biosynthesis of APP in a
      physiological context and illuminate the occurrence of two pools of APP, one of
      which is linked to neuroendocrine cell activation.

PMID- 16092945
TI  - Neurotoxicity and behavioral deficits associated with Septin 5 accumulation in
      dopaminergic neurons.
AB  - Septin 5, a parkin substrate, is a vesicle- and membrane-associated protein that
      plays a significant role in inhibiting exocytosis. The regulatory function of
      Septin 5 in dopaminergic (DAergic) neurons of substantia nigra (SN), maintained
      at relatively low levels, has not yet been delineated. As loss of function
      mutations of parkin are the principal cause of a familial Parkinson's disease, a
      prevailing hypothesis is that the loss of parkin activity results in accumulation
      of Septin 5 which confers neuron-specific toxicity in SN-DAergic neurons. In
      vitro and in vivo models were used to support this hypothesis. In our well
      characterized DAergic SN4741 cell model, acute accumulation of elevated levels of
      Septin 5, but not synphilin-1 (another parkin substrate), resulted in cytotoxic
      cell death that was markedly reduced by parkin co-transfection. A transgenic
      mouse model expressing a dominant negative parkin mutant accumulated moderate
      levels of Septin 5 in SN-DAergic neurons. These mice acquired a progressive l
      DOPA responsive motor dysfunction that developed despite a 25% higher than normal
      level of striatal dopamine (DA) and no apparent loss of DAergic neurons. The
      phenotype of this animal, increased striatal dopamine and reduced motor function,
      was similar to that observed in parkin knockout animals, suggesting a common
      DAergic alteration. These data suggest that a threshold level of Septin 5
      accumulation is required for DAergic cell loss and that l-DOPA-responsive motor
      deficits can occur even in the presence of elevated DA.

PMID- 16092944
TI  - Inhibition of Rac GTPase triggers a c-Jun- and Bim-dependent mitochondrial
      apoptotic cascade in cerebellar granule neurons.
AB  - Rho GTPases are key transducers of integrin/extracellular matrix and growth
      factor signaling. Although integrin-mediated adhesion and trophic support
      suppress neuronal apoptosis, the role of Rho GTPases in neuronal survival is
      unclear. Here, we have identified Rac as a critical pro-survival GTPase in
      cerebellar granule neurons (CGNs) and elucidated a death pathway triggered by its
      inactivation. GTP-loading of Rac1 was maintained in CGNs by integrin-mediated
      (RGD-dependent) cell attachment and trophic support. Clostridium difficile toxin
      B (ToxB), a specific Rho family inhibitor, induced a selective caspase-mediated
      degradation of Rac1 without affecting RhoA or Cdc42 protein levels. Both ToxB and
      dominant-negative N17Rac1 elicited CGN apoptosis, characterized by cytochrome c
      release and activation of caspase-9 and -3, whereas dominant-negative N19RhoA or
      N17Cdc42 did not cause significant cell death. ToxB stimulated mitochondrial
      translocation and conformational activation of Bax, c-Jun activation, and
      induction of the BH3-only protein Bim. Similarly, c-Jun activation and Bim
      induction were observed with N17Rac1. A c-jun N-terminal protein kinase (JNK)/p38
      inhibitor, SB203580, and a JNK-specific inhibitor, SP600125, significantly
      decreased ToxB-induced Bim expression and blunted each subsequent step of the
      apoptotic cascade. These results indicate that Rac acts downstream of integrins
      and growth factors to promote neuronal survival by repressing c-Jun/Bim-mediated
      mitochondrial apoptosis.

PMID- 16092946
TI  - High-affinity peripheral benzodiazepine receptor ligand, PK11195, regulates
      protein phosphorylation in rat brain mitochondria under control of Ca(2+).
AB  - The effects of PK11195, a high-affinity peripheral benzodiazepine receptor (PBR)
      ligand, on protein phosphorylation in isolated purified rat brain mitochondria
      were investigated. The isoquinoline carboxamide ligand of PBR, PK11195, but not
      the benzodiazepine ligand Ro5-4864, in the nanomolar concentration range strongly
      increased the phosphorylation of 3.5 and 17 kDa polypeptides. The effect of
      PK11195 was seen in the presence of elevated Ca(2+) levels (3 x 10(-7) to 10(-6)
      m), but not at very low Ca(2+) levels (10(-8) to 3 x 10(-8) m). This indicates
      that PBR involves Ca(2+) as a second messenger in the regulation of protein
      phosphorylation. Staurosporine, an inhibitor of protein kinase activity was able
      to suppress the PK11195-promoted protein phosphorylation. When the permeability
      transition pore (PTP) was opened by threshold Ca(2+) load, phosphorylation of the
      3.5-kDa polypeptide was diminished, but strong phosphorylation of the 43-kDa
      protein was revealed. The 43-kDa protein appears to be a PTP-specific
      phosphoprotein. If PTP was opened, PK11195 did not increase the phosphorylation
      of the 3.5 and 17-kDa proteins but suppressed the phosphorylation of the PTP
      specific 43-kDa phosphoprotein. The ability of PK11195 to increase the protein
      phosphorylation, which was lost under Ca(2+)-induced PTP opening, was restored
      again in the presence of calmidazolium, an antagonist of calmodulin and inhibitor
      of protein phosphatase PP2B. These results show a tight interaction of PBR with
      the PTP complex in rat brain mitochondria. In conclusion, a novel function of PBR
      in brain mitochondria has been revealed, and the PBR-mediated protein
      phosphorylation has to be considered an important element of the PBR-associated
      signal transducing cascades in mitochondria and cells.

PMID- 16092947
TI  - alpha-Linolenic acid does not contribute appreciably to docosahexaenoic acid
      within brain phospholipids of adult rats fed a diet enriched in docosahexaenoic
      acid.
AB  - Adult male unanesthetized rats, reared on a diet enriched in both alpha-linolenic
      acid (alpha-LNA) and docosahexaenoic acid (DHA), were infused intravenously for 5
      min with [1-(14)C]alpha-LNA. Timed arterial samples were collected until the
      animals were killed at 5 min and the brain was removed after microwaving. Plasma
      and brain lipid concentrations and radioactivities were measured. Within plasma
      lipids, > 99% of radioactivity was in the form of unchanged [1-(14)C]alpha-LNA.
      Eighty-six per cent of brain radioactivity at 5 min was present as beta-oxidation
      products, whereas the remainder was mainly in 'stable' phospholipid or
      triglyceride as alpha-LNA or DHA. Equations derived from kinetic modeling
      demonstrated that unesterified unlabeled alpha-LNA rapidly enters brain from
      plasma, but that its incorporation into brain phospholipid and triglyceride, as
      in the form of synthesized DHA, is < or = 0.2% of the amount that enters the
      brain. Thus, in rats fed a diet containing large amounts of both alpha-LNA and
      DHA, the alpha-LNA that enters brain from plasma largely undergoes beta
      oxidation, and is not an appreciable source of DHA within brain phospholipids.

PMID- 16092948
TI  - Gap junction blockage limits intercellular spreading of astrocytic apoptosis
      induced by metabolic depression.
AB  - Astrocytes are highly coupled by gap junction channels, which allow transfer of
      intracellular signalling molecules and metabolites between connected cells.
      Astrocytic gap junctions remain open during ischemic conditions as previously
      demonstrated in vitro and in situ. In this study, we investigated the effect of
      gap junction blockage on iodoacetate-induced ATP depression and cell death
      progression in astrocytes in primary rat hippocampal cultures. We demonstrated
      that blockage of gap junctions during iodoacetate-induced inhibition of the
      glycolysis induced an earlier onset of the ATP depression. Moreover, initiation
      of apoptotic processes, demonstrated by binding of Annexin V, was critically
      dependent on the ATP levels. The apoptotic event was also shown to spread and
      involve neighbouring cells, a process that was inhibited by blockage of gap
      junction communication. Chelating intracellular calcium using BAPTA-AM
      decelerated the iodoacetate-induced ATP depression. The chelation also
      decelerated the spreading of apoptotic processes. Inhibition of caspases did not
      alter the expansion of cell groups being Annexin V positive. However, the
      proportion of Annexin V positive cells also being propidium iodide positive was
      increased after caspase inhibition. The results show that inhibition of gap
      junctions during cellular metabolic depression interferes with the metabolic
      status and cell death progression in astrocytes.

PMID- 16092949
TI  - Topiramate reduces AMPA-induced Ca(2+) transients and inhibits GluR1 subunit
      phosphorylation in astrocytes from primary cultures.
AB  - Topiramate (TPM) is a structurally novel broad spectrum anticonvulsant known to
      have a negative modulatory effect on the alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA)/kainate subtypes of glutamate receptors and some
      types of voltage-gated Na(+) and Ca(2+) channels, and a positive modulatory
      effect on some types of gamma-aminobutyric acid(A) (GABA(A)) receptors and at
      least one type of K(+) channels in neurons. In an earlier work, we showed that
      the negative modulatory effect of TPM (100 mum) on AMPA/kainate receptors in
      neurons is dependent on TPM modulation of the phosphorylation state of these
      receptors. In this work, we investigated the effect of TPM on AMPA-induced
      intracellular calcium ([Ca(2+)](i)) responses in cultured rat cortical
      astrocytes, with special interest in intracellular mechanisms. Here, we report
      that the ability of TPM (1-100 mum) to inhibit AMPA-induced accumulation of
      Ca(2+) in astrocytes is inversely related to the level of protein kinase A (PKA) 
      mediated phosphorylation of channels activated by AMPA. The level of receptor
      phosphorylation was further determined with western blot using phosphorylation
      specific antibodies that recognize the glutamate receptor 1 (GluR1) subunit
      phosphorylated on Ser845. These results demonstrated that, even in cultured
      cortical astrocytes, TPM significantly reduced the phophorylation level of GluR1
      subunits. Furthermore, it was shown that TPM binds to AMPA receptors in the
      dephosphorylated state and thereby exerts an allosteric modulatory effect on the
      ion channel.

PMID- 16092950
TI  - Evidence that gabapentin reduces neuropathic pain by inhibiting the spinal
      release of glutamate.
AB  - Gabapentin is an anticonvulsant that successfully treats many neuropathic pain
      syndromes, although the mechanism of its antihyperalgesic action remains elusive.
      This study aims to help delineate gabapentin's antihyperalgesic mechanisms. We
      assessed the effectiveness of gabapentin at decreasing mechanical and cold
      hypersensitivity induced in a rat model of neuropathic pain. Thus, we compared
      the effectiveness of pre- or post-treatment with systemic or intrathecal (i.t.)
      gabapentin at reducing the development and maintenance of the neuropathic pain
      symptoms. Gabapentin successfully decreased mechanical and cold hypersensitivity,
      both as a pretreatment and post-treatment. Furthermore, both i.t. and systemic
      administration of gabapentin were effective in reducing the behavioral
      hypersensitivity; however, the i.t. administration was superior to the systemic.
      We also examined gabapentin's effects at inhibiting hindpaw formalin-induced
      release of excitatory amino acids (EAAs) in the spinal cord dorsal horn (SCDH)
      both in naive rats and in rats with neuropathic pain. We present the first
      evidence that gabapentin reduces the formalin-induced release of both glutamate
      and aspartate in SCDH. Furthermore, i.t. gabapentin reduces the enhanced noxious
      stimulus-induced spinal release of glutamate seen in neuropathic rats. These data
      suggest that gabapentin reduces neuropathic pain symptoms by inhibiting the
      release of glutamate in the SCDH.

PMID- 16092951
TI  - Insulin modulates hippocampal activity-dependent synaptic plasticity in a N
      methyl-d-aspartate receptor and phosphatidyl-inositol-3-kinase-dependent manner.
AB  - Insulin and its receptor are both present in the central nervous system and are
      implicated in neuronal survival and hippocampal synaptic plasticity. Here we show
      that insulin activates phosphatidylinositol 3-kinase (PI3K) and protein kinase B
      (PKB), and results in an induction of long-term depression (LTD) in hippocampal
      CA1 neurones. Evaluation of the frequency-response curve of synaptic plasticity
      revealed that insulin induced LTD at 0.033 Hz and LTP at 10 Hz, whereas in the
      absence of insulin, 1 Hz induced LTD and 100 Hz induced LTP. LTD induction in the
      presence of insulin required low frequency synaptic stimulation (0.033 Hz) and
      blockade of GABAergic transmission. The LTD or LTP induced in the presence of
      insulin was N-methyl-d-aspartate (NMDA) receptor specific as it could be
      inhibited by alpha-amino-5-phosphonopentanoic acid (APV), a specific NMDA
      receptor antagonist. LTD induction was also facilitated by lowering the
      extracellular Mg(2+) concentration, indicating an involvement of NMDA receptors.
      Inhibition of PI3K signalling or discontinuing synaptic stimulation also
      prevented this LTD. These results show that insulin modulates activity-dependent
      synaptic plasticity, which requires activation of NMDA receptors and the PI3K
      pathway. The results obtained provide a mechanistic link between insulin and
      synaptic plasticity, and explain how insulin functions as a neuromodulator.

PMID- 16092953
TI  - Crystal structure of nitrogen regulatory protein IIANtr from Neisseria
      meningitidis.
AB  - BACKGROUND: The NMB0736 gene of Neisseria meningitidis serogroup B strain MC58
      encodes the putative nitrogen regulatory protein, IIANtr (abbreviated to NM
      IIANtr). The homologous protein present in Escherichia coli is implicated in the
      control of nitrogen assimilation. As part of a structural proteomics approach to
      the study of pathogenic Neisseria spp., we have selected this protein for
      structure determination by X-ray crystallography. RESULTS: The NM-IIANtr was over
      expressed in E. coli and was shown to be partially mono-phosphorylated, as
      assessed by mass spectrometry of the purified protein. Crystals of un
      phosphorylated protein were obtained and diffraction data collected to 2.5 A
      resolution. The structure of NM-IIANtr was solved by molecular replacement using
      the coordinates of the E. coli nitrogen regulatory protein IIAntr [PDB: 1A6J] as
      the starting model. The overall fold of the Neisseria enzyme shows a high degree
      of similarity to the IIANtr from E. coli, and the position of the phosphoryl
      acceptor histidine residue (H67) is conserved. The orientation of an adjacent
      arginine residue (R69) suggests that it may also be involved in coordinating the
      phosphate group. Comparison of the structure with that of E. coli IIAmtl
      complexed with HPr [PDB: 1J6T] indicates that NM-IIANtr binds in a similar way to
      the HPr-like enzyme in Neisseria. CONCLUSION: The structure of NM-IIANtr confirms
      its assignment as a homologue of the IIANtr proteins found in a range of other
      Gram-negative bacteria. We conclude that the NM- IIANtr protein functions as part
      of a phosphorylation cascade which, in contrast to E. coli, shares the upstream
      phosphotransfer protein with the sugar uptake phosphoenolpyruvate:sugar
      phosphotransferase system (PTS), but in common with E. coli has a distinct
      downstream effector mechanism.

PMID- 16092954
TI  - The macular mapping test: a reliability study.
AB  - BACKGROUND: Age-related macular degeneration (ARMD) is the leading cause of
      visual disability in people over 60 years of age in the developed world. The
      success of treatment deteriorates with increased latency of diagnosis. The
      purpose of this study was to determine the reliability of the macular mapping
      test (MMT), and to investigate its potential as a screening tool. METHODS: The
      study population comprised of 31 healthy eyes of 31 participants. To assess
      reliability, four macular mapping test (MMT) measurements were taken in two
      sessions separated by one hour by two practitioners, with reversal of order in
      the second session. MMT readings were also taken from 17 age-related maculopathy
      (ARM), and 12 AMD affected eyes. RESULTS: For the normal cohort, average MMT
      scores ranged from 85.5 to 100.0 MMT points. Scores ranged from 79.0 to 99.0 for
      the ARM group and from 9.0 to 92.0 for the AMD group. MMT scores were reliable to
      within +/- 7.0 points. The difference between AMD affected eyes and controls (z =
      3.761, p = < 0.001) was significant. The difference between ARM affected eyes and
      controls was not significant (z = -0.216, p = 0.829). CONCLUSION: The reliability
      data shows that a change of 14 points or more is required to indicate a
      clinically significant change. This value is required for use of the MMT as an
      outcome measure in clinical trials. Although there was no difference between MMT
      scores from ARM affected eyes and controls, the MMT has the advantage over the
      Amsler grid in that it uses a letter target, has a peripheral fixation aid, and
      it provides a numerical score. This score could be beneficial in office and home
      monitoring of AMD progression, as well as an outcome measure in clinical
      research.

PMID- 16092955
TI  - Subluxation: dogma or science?
AB  - Subluxation syndrome is a legitimate, potentially testable, theoretical construct
      for which there is little experimental evidence. Acceptable as hypothesis, the
      widespread assertion of the clinical meaningfulness of this notion brings
      ridicule from the scientific and health care communities and confusion within the
      chiropractic profession. We believe that an evidence-orientation among
      chiropractors requires that we distinguish between subluxation dogma vs.
      subluxation as the potential focus of clinical research. We lament efforts to
      generate unity within the profession through consensus statements concerning
      subluxation dogma, and believe that cultural authority will continue to elude us
      so long as we assert dogma as though it were validated clinical theory.

PMID- 16092956
TI  - Characterization of insulin-like-growth factor II (IGF II) mRNA positive hepatic
      altered foci and IGF II expression in hepatocellular carcinoma during
      diethylnitrosamine-induced hepatocarcinogenesis in rats.
AB  - BACKGROUND: Insulin-like-growth factor II (IGF II) has been implicated in the
      pathogenesis of neoplasm of different tissues, including liver of rats and men.
      This growth factor is believed to exert its effect during cellular proliferation.
      During the process of development of hepatocellular carcinoma (HCC), different
      hepatic altered foci appear. They are believed to be the putative precursors of
      HCC in rats and in men. Thus, to study the role of the gene in a defined model of
      hepatocarcinogenesis was the target to elucidate its role in various cancer
      phenotypes during the entire development stage of cancer, right from earlier
      preneoplastic lesions to HCC. METHODS: Antisense in situ hybridization technique
      was used here to characterize the type(s) of foci in which IGF II mRNA had
      expressed during the development of hepatocarcinogenesis-induced by
      diethylnitrosamine and promoted by phenobarbital in rats. Various focal lesions
      have been categorized depending on the stages and sizes along with IGF II
      expression patterns in them. Immunohistochemical detection for proliferating cell
      nuclear antigen (PCNA) was made to detect the role of the gene in preneoplastic
      and neoplastic cellular proliferation. RESULTS: IGF II expression was located in
      the glycogen-storage acidophilic cell foci maximally followed by mixed cell
      lesions and the least in basophilic lesions. The expression of IGF II was found
      to be predominant in the HCC. The expression of gene was also located at the
      peripheral cells of spongiosis hepatis which are believed to be the precursor of
      ito cell carcinoma. It was noted that there is a direct correlation between IGF
      II expression and immunohistochemical detection for PCNA. CONCLUSION: It may be
      concluded that IGF II gene expression plays an important role during the
      development of neoplasia and the gene expresses in the sequence of events leading
      from glycogen-rich-acidophilic lesions to glycogen poor basophilic lesions to HCC
      with an expression pattern of "high-low-high" in terms of degree of expression.
      Moreover, the essential role of the gene at the immediate initiation stage of
      carcinogenesis (first few weeks) and during HCC development cannot be ignored.
      Thus this expression can be used as a suitable marker for very early detection of
      the cancerous process and can save numbers of future cancer victims by very early
      detection of this disease.

PMID- 16092957
TI  - A survey of transcutaneous blood gas monitoring among European neonatal intensive
      care units.
AB  - BACKGROUND: PCO2 and PO2 are important monitoring parameters in neonatal
      intensive care units (NICU). Compared to conventional blood gas measurements that
      cause significant blood loss in preterms, transcutaneous (tc) measurements allow
      continuous, non-invasive monitoring of blood gas levels. The aim of the study was
      to survey the usage and opinions among German speaking NICUs concerning tc blood
      gas monitoring. METHODS: A questionnaire was developed and sent to 56 head nurses
      of different NICUs in Germany, Switzerland and Austria. RESULTS: A completely
      answered questionnaire was obtained from 41 NICUs. In two of these units tc
      measurements are not performed. In most NICUs (77%), both PtcO2 and PtcCO2 are
      measured simultaneously. Most units change the sensors every 3 hours; however,
      the recommended temperature of 44 degrees C is used in only 15% of units. In only
      8% of units are arterial blood gases obtained to validate tc values. Large
      variations were found concerning the targeted level of oxygen saturation [median
      upper limit: 95% (range 80-100%); median lower limit: 86% (range 75-93%)] and PO2
      [median upper limit: 70 mmHg (range 45-90 mmHg); median lower limit: 44 mmHg
      (range 30-60 mmHg)]. CONCLUSION: Our survey shows that the use of tc monitors
      remains widespread among German speaking NICUs, despite earlier data suggesting
      that their use had been abandoned in many NICUs worldwide. In addition, we
      suggest that the current method of monitoring oxygenation may not prevent
      hyperoxemia in preterm infants.

PMID- 16092958
TI  - An evaluation of a morphine public health programme for cancer and AIDS pain
      relief in Sub-Saharan Africa.
AB  - BACKGROUND: Despite growing HIV and cancer prevalence in Sub-Saharan Africa, and
      WHO advocacy for a public health approach to palliative care provision, opioid
      availability is severely limited. Uganda has achieved a morphine roll-out
      programme in partnership with the Ministry of Health. This study aimed to
      evaluate that programme by identifying challenges to implementation that may
      inform replication. METHODS: A multi-methods protocol appraised morphine
      regulation, storage, prescribing, and consumption in three phases: key informant
      interviews throughout the opioid supply chain, and direct observation and audit
      of clinical practice. RESULTS: Regulation had achieved its goal of preventing
      misuse and leakage from the supply chain. However, the Government felt that
      relaxation of regulation was now appropriate. Confusion and complexity in storage
      and authorization rules led to discontinuation of opioid pain management at the
      patient level and also wasted service time in trying to obtain supplies to which
      they were entitled. Continued neglect to prescribe among clinicians and public
      fear of opioids led to under prescribing, and clinical skills showed some
      evidence of need for improvement with respect to physical assessment and follow
      up. CONCLUSION: The Ugandan programme offers a successful model for both advocacy
      and Governmental support in achieving opioid roll-out across health districts.
      Despite initial concerns, abuse of opioids has not been evident. Further work is
      required to ensure that available supplies of opioids are prescribed to those in
      need, and that clinical standards are met. However, the programme for roll-out
      has proved a useful model to expand opioid availability as the first step in
      improving patient care, and may prove a useful template for other Sub-Saharan
      African countries.

PMID- 16092959
TI  - Assessing poisoning risks related to storage of household hazardous materials:
      using a focus group to improve a survey questionnaire.
AB  - BACKGROUND: In fall of 2004, the authors began an investigation to characterize
      the correlations between the storage of Household Hazardous Materials and the
      associated health risks, particularly to children. The study area selected was
      Genesee County, Michigan, near Flint, with data to be collected by a phone survey
      of residents and through the acquisition of county hospital records containing
      procedure codes indicating treatment for poison emergencies, and review of poison
      control center data. METHODS: A focus group was used to identify key topics and
      relationships within these data for improving the phone survey questionnaire and
      its analysis. RESULTS: The focus group was successful in identifying the key
      issues with respect to all the data collection objectives, resulting in a
      significantly shorter and more topically focused survey questionnaire. Execution
      time of the phone survey decreased from 30 to 12 minutes, and useful
      relationships between the data were revealed, e.g., the linkage between reading
      food labels and reading labels on containers containing potentially harmful
      substances. CONCLUSION: Focus groups and their preparatory planning can help
      reveal data interrelationships before larger surveys are undertaken. Even where
      time and budget constraints prevent the ability to conduct a series of focus
      groups, one successful focus group session can improve survey performance and
      reduce costs.

PMID- 16092960
TI  - Which resources should be used to identify RCT/CCTs for systematic reviews: a
      systematic review.
AB  - BACKGROUND: Systematic reviewers seek to comprehensively search for relevant
      studies and summarize these to present the most valid estimate of intervention
      effectiveness. The more resources searched, the higher the yield, and thus time
      and costs required to conduct a systematic review. While there is an abundance of
      evidence to suggest how extensive a search for randomized controlled trials
      (RCTs) should be, it is neither conclusive nor consistent. This systematic review
      was conducted in order to assess the value of different resources to identify
      trials for inclusion in systematic reviews. METHODS: Seven electronic databases,
      four journals and Cochrane Colloquia were searched. Key authors were contacted
      and references of relevant articles screened. Included studies compared two or
      more sources to find RCTs or controlled clinical trials (CCTs). A checklist was
      developed and applied to assess quality of reporting. Data were extracted by one
      reviewer and checked by a second. Medians and ranges for precision and recall
      were calculated; results were grouped by comparison. Meta-analysis was not
      performed due to large heterogeneity. Subgroup analyses were conducted for:
      search strategy (Cochrane, Simple, Complex, Index), expertise of the searcher
      (Cochrane, librarian, non-librarian), and study design (RCT and CCT). RESULTS:
      Sixty-four studies representing 13 electronic databases met inclusion criteria.
      The most common comparisons were MEDLINE vs. handsearching (n = 23), MEDLINE vs.
      MEDLINE+handsearching (n = 13), and MEDLINE vs. reference standard (n = 13).
      Quality was low, particularly for the reporting of study selection methodology.
      Overall, recall and precision varied substantially by comparison and ranged from
      0 to 100% and 0 to 99%, respectively. The trial registries performed the best
      with median recall of 89% (range 84, 95) and median precision of 96.5% (96, 97),
      although these results are based on a small number of studies. Inadequate or
      inappropriate indexing was the reason most cited for missing studies. Complex and
      Cochrane search strategies (SS) performed better than Simple SS. CONCLUSION:
      Multiple-source comprehensive searches are necessary to identify all RCTs for a
      systematic review, although indexing needs to be improved. Although trial
      registries demonstrated the highest recall and precision, the Cochrane SS or a
      Complex SS in consultation with a librarian are recommended. Continued efforts to
      develop CENTRAL should be supported.

PMID- 16092961
TI  - Health-related quality of life in patients with pulmonary arterial hypertension.
AB  - BACKGROUND: Improved outcomes with expanding treatment options for patients with
      pulmonary arterial hypertension present the opportunity to consider additional
      end-points in approaching therapy, including factors that influence health
      related quality of life. However, comparatively little is known about health
      related quality of life and its determinants in patients with pulmonary arterial
      hypertension. METHODS: Health-related quality of life was evaluated in a cross
      sectional study of 155 outpatients with pulmonary arterial hypertension using
      generic and respiratory-disease specific measurement tools. Most patients had
      either World Health Organization functional Class II or III symptoms.
      Demographic, hemodynamic and treatment variables were assessed for association
      with health-related quality of life scores. RESULTS: Patients with pulmonary
      arterial hypertension suffered severe impairments in both physical and emotional
      domains of health-related quality of life. Patients with idiopathic ("primary")
      pulmonary arterial hypertension had the best, and those with systemic sclerosis
      the worst health-related quality of life. Greater six-minute walk distance
      correlated with better health-related quality of life scores, as did functional
      Class II versus Class III symptoms. Hemodynamic measurements, however, did not
      correlate with health-related quality of life scores. No differences in health
      related quality of life were found between patients who were being treated with
      calcium channel antagonists, bosentan or continuously infused epoprostenol at the
      time of quality of life assessment. CONCLUSION: Health-related quality of life is
      severely impaired in patients with pulmonary arterial hypertension and is
      associated with measures of functional status. Specific associations with
      impaired health-related quality of life suggest potential areas for targeted
      intervention.

PMID- 16092962
TI  - Use of endogenous retroviral sequences (ERVs) and structural markers for
      retroviral phylogenetic inference and taxonomy.
AB  - BACKGROUND: Endogenous retroviral sequences (ERVs) are integral parts of most
      eukaryotic genomes and vastly outnumber exogenous retroviruses (XRVs). ERVs with
      a relatively complete structure were retrieved from the genetic archives of
      humans and chickens, diametrically opposite representatives of vertebrate
      retroviruses (over 3300 proviruses), and analyzed, using a bioinformatic program,
      RetroTector, developed by us. This rich source of proviral information,
      accumulated in a local database, and a collection of XRV sequences from the
      literature, allowed the reconstruction of a Pol based phylogenetic tree, more
      extensive than previously possible. The aim was to find traits useful for
      classification and evolutionary studies of retroviruses. Some of these traits
      have been used by others, but they are here tested in a wider context than
      before. RESULTS: In the ERV collection we found sequences similar to the XRV
      based genera: alpha-, beta-, gamma-, epsilon- and spumaretroviruses. However, the
      occurrence of intermediates between them indicated an evolutionary continuum and
      suggested that taxonomic changes eventually will be necessary. No delta or
      lentivirus representatives were found among ERVs. Classification based on Pol
      similarity is congruent with a number of structural traits. Acquisition of
      dUTPase occurred three times in retroviral evolution. Loss of one or two NC zinc
      fingers appears to have occurred several times during evolution. Nucleotide
      biases have been described earlier for lenti-, delta- and betaretroviruses and
      were here confirmed in a larger context. CONCLUSION: Pol similarities and other
      structural traits contribute to a better understanding of retroviral phylogeny.
      "Global" genomic properties useful in phylogenies are i.) translational strategy,
      ii.) number of Gag NC zinc finger motifs, iii.) presence of Pro N-terminal
      dUTPase (dUTPasePro), iv.) presence of Pro C-terminal G-patch and v.) presence of
      a GPY/F motif in the Pol integrase (IN) C-terminal domain. "Local" retroviral
      genomic properties useful for delineation of lower level taxa are i.) host
      species range, ii.) nucleotide compositional bias and iii.) LTR lengths.

PMID- 16092963
TI  - Spam1-associated transmission ratio distortion in mice: elucidating the
      mechanism.
AB  - BACKGROUND: While transmission ratio distortion, TRD, (a deviation from Mendelian
      ratio) is extensive in humans and well-documented in mice, the underlying
      mechanisms are unknown. Our earlier studies on carriers of spontaneous mutations
      of mouse Sperm Adhesion Molecule 1 (Spam1) suggested that TRD results from
      biochemically different sperm, due to a lack of transcript sharing through the
      intercellular cytoplasmic bridges of spermatids. These bridges usually allow
      transcript sharing among genetically different spermatids which develop into
      biochemically and functionally equivalent sperm. OBJECTIVES: The goals of the
      study were to provide support for the lack of sharing (LOS) hypothesis, using
      transgene and null carriers of Spam1, and to determine the mechanism of Spam1
      associated TRD. METHODS: Carriers of Spam1-Hyal5 BAC transgenes were mated with
      wild-type female mice and the progeny analyzed for TRD by PCR genotyping. Sperm
      from transgene and Spam1 null carriers were analyzed using flow cytometry and
      immunocytochemistry to detect quantities of Spam1 and/or Hyal5. Transgene-bearing
      sperm with Spam1 overexpression were detected by fluorescence in situ
      hybridization. In wild-type animals, EM studies of in situ transcript
      hybridization of testis sections and Northern analysis of biochemically
      fractionated testicular RNA were performed to localize Spam1 transcript. Finally,
      AU-rich motifs identified in the 3' UTR of Spam1 RNA were assayed by UV cross
      linking to determine their ability to interact with testicular RNA binding
      proteins. RESULTS: The Tg8 line of transgene carriers had a significant (P <
      0.001) TRD, due to reduced fertilizing ability of transgene-bearing sperm. These
      sperm retained large cytoplasmic droplets engorged with overexpressed Spam1 or
      Hyal5 protein. Caudal sperm from transgene carriers and caput sperm of null
      carriers showed a bimodal distribution of Spam1, indicating that the sperm in a
      male were biochemically different with respect to Spam1 quantities. Spam1 RNA was
      absent from the bridges, associated exclusively with the ER, and was shown to be
      anchored to the cytoskeleton. This compartmentalization of the transcript,
      mediated by cytoskeletal binding, occurs via protein interactions with 3' UTR AU
      rich sequences that are likely involved in its stabilization. CONCLUSION: We
      provide strong support for the LOS hypothesis, and have elucidated the mechanism
      of Spam1-associated TRD.

PMID- 16092964
TI  - Wastage in the health workforce: some perspectives from African countries.
AB  - BACKGROUND: Sub-Saharan Africa faces a human resources crisis in the health
      sector. Over the past two decades its population has increased substantially,
      with a significant rise in the disease burden due to HIV/AIDS and recurrent
      communicable diseases and an increased incidence of noncommunicable diseases.
      This increased demand for health services is met with a rather low supply of
      health workers, but this notwithstanding, sub-Saharan African countries also
      experience significant wastage of their human resources stock. METHODS: This
      paper is a desk review to illustrate suggestions that the way human resources for
      health (HRH) are trained and deployed in Africa does not enhance productivity and
      that countries are unable to realize the full potential expected from the working
      life of their health workers. The paper suggests data types for use in measuring
      various forms of "wastage". RESULTS: "Direct" wastage--or avoidable increases in
      loss of staff through factors such as emigration and death--is on the rise,
      perhaps as a result of the HIV/AIDS epidemic. "Indirect" wastage--which is the
      result of losses in output and productivity from health professionals' misapplied
      skills, absenteeism, poor support and lack of supervision--is also common.
      HIV/AIDS represents a special cause of wastage in Africa. Deaths of health
      workers, fear of infection, burnout, absenteeism, heavy workloads and stress
      affect productivity. CONCLUSION: The paper reviews strategies that have been
      proposed and/or implemented. It suggests areas needing further attention,
      including: developing and using indicators for monitoring and managing wastage;
      enhancing motivation and morale of health workers; protecting and valuing the
      health worker with enhanced occupational safety and welfare systems; and
      establishing the moral leadership to effectively tackle HIV/AIDS and the brain
      drain.

PMID- 16092965
TI  - Modern classification of neoplasms: reconciling differences between morphologic
      and molecular approaches.
AB  - BACKGROUND: For over 150 years, pathologists have relied on histomorphology to
      classify and diagnose neoplasms. Their success has been stunning, permitting the
      accurate diagnosis of thousands of different types of neoplasms using only a
      microscope and a trained eye. In the past two decades, cancer genomics has
      challenged the supremacy of histomorphology by identifying genetic alterations
      shared by morphologically diverse tumors and by finding genetic features that
      distinguish subgroups of morphologically homogeneous tumors. DISCUSSION: The
      Developmental Lineage Classification and Taxonomy of Neoplasms groups neoplasms
      by their embryologic origin. The putative value of this classification is based
      on the expectation that tumors of a common developmental lineage will share
      common metabolic pathways and common responses to drugs that target these
      pathways. The purpose of this manuscript is to show that grouping tumors
      according to their developmental lineage can reconcile certain fundamental
      discrepancies resulting from morphologic and molecular approaches to neoplasm
      classification. In this study, six issues in tumor classification are described
      that exemplify the growing rift between morphologic and molecular approaches to
      tumor classification: 1) the morphologic separation between epithelial and non
      epithelial tumors; 2) the grouping of tumors based on shared cellular functions;
      3) the distinction between germ cell tumors and pluripotent tumors of non-germ
      cell origin; 4) the distinction between tumors that have lost their
      differentiation and tumors that arise from uncommitted stem cells; 5) the
      molecular properties shared by morphologically disparate tumors that have a
      common developmental lineage, and 6) the problem of re-classifying
      morphologically identical but clinically distinct subsets of tumors. The
      discussion of these issues in the context of describing different methods of
      tumor classification is intended to underscore the clinical value of a robust
      tumor classification. SUMMARY: A classification of neoplasms should guide the
      rational design and selection of a new generation of cancer medications targeted
      to metabolic pathways. Without a scientifically sound neoplasm classification,
      biological measurements on individual tumor samples cannot be generalized to
      class-related tumors, and constitutive properties common to a class of tumors
      cannot be distinguished from uninformative data in complex and chaotic biological
      systems. This paper discusses the importance of biological classification and
      examines several different approaches to the specific problem of tumor
      classification.

PMID- 16092966
TI  - Specific IgE response to purified and recombinant allergens in latex allergy.
AB  - BACKGROUND: In recent years, allergy to natural rubber latex has emerged as a
      major allergy among certain occupational groups and patients with underlying
      diseases. The sensitization and development of latex allergy has been attributed
      to exposure to products containing residual latex proteins. Although improved
      manufacturing procedures resulted in a considerable reduction of new cases, the
      potential risk for some patient groups is still great. In addition the prevalent
      cross-reactivity of latex proteins with other food allergens poses a major
      concern. A number of purified allergens and a few commercial kits are currently
      available, but no concerted effort was undertaken to evaluate them. METHODS: We
      studied 11 purified latex allergens, Hev b 1 to Hev b 10, and Hev b 13 along with
      several crude allergen extracts and two commercial ImmunoCAP assays to evaluate
      specific IgE antibody in the sera from latex allergic patients and controls.
      Health care workers and spina bifida patients with clinical symptoms of latex
      allergy, spina bifida patients without latex allergy, and non-atopic health care
      workers have been studied. RESULTS: The results suggest that Hev b 2, 5, 6, and
      13 together identified over 80 percent health care workers with latex allergy,
      while Hev b 6 along with Hev b 1 or 3 detected specific IgE antibody in all sera
      studied from patients with spina bifida and latex allergy. The ImmunoCAP results
      using both Hev b 5 amplified and non-amplified closely agreed with the clinical
      diagnosis of latex allergy in health care workers and in spina bifida.
      CONCLUSION: Although the purified allergens and crude extracts reacted diversely
      with IgE from different patient groups, the results indicated that use of certain
      combinations of purified recombinant antigens will be useful in commercial kits
      or in in-house assays for detecting specific IgE antibody in the sera. The
      results suggest that a combination of Hev b 2, 3, 5, 6, and 13 together detected
      specific IgE in 80% of the sera from latex allergic patients. Both ImmunoCAPs
      correctly identified over 95% of latex allergic patients, however, showed
      reactivity with a few normal control subjects.

PMID- 16092967
TI  - mRNA expression and localization of bNOS, eNOS and iNOS in human cervix at
      preterm and term labour.
AB  - BACKGROUND: Preterm birth is the primary cause of the neonatal mortality and
      morbidity. There will be no preterm birth without a cervical softening. Nitric
      oxide (NO) is shown to be a mediator of term cervical ripening. The aim of this
      study was to investigate mRNA expression of the three isomers of NO synthases
      (NOS) and to identify them by immunohistochemistry in the human cervix at preterm
      birth compared to term. METHODS: The three isomers of NOS--inducible (iNOS),
      endothelial (eNOS) and neuronal (bNOS)--were investigated in the human cervix.
      The expression of mRNA was determined using Real-Time Multiplex RT-PCR. The
      localisation of synthases in the cervical tissue was analysed using
      immunohistochemistry. Cervical biopsies were obtained from 4 groups of women
      without clinical signs of infection: preterm (PTL), term labour (TL), preterm not
      in labour (PTnotL) and term not in labour (TnotL) patients. One-Way ANOVA,
      Kruskal-Wallis, Student t-test or Mann-Whitney test were applied as appropriate
      to determine statistically significant differences among the groups. RESULTS:
      Patients in preterm labour had significantly (p < 0.01) higher mRNA levels of all
      the three NOS isomers compared to those in term labour. Women not in labour,
      irrespective of gestational age, thus with unripe cervices, had significantly
      lower eNOS mRNA levels compared to those in labour (p < 0.01). Immunoreactivity
      for all three NO synthases was observed in each examined sample in all groups.
      The bNOS staining was the most prominent. CONCLUSION: The mRNA levels were higher
      in the preterm labour group compared to the women at term labour. The significant
      increase of the eNOS mRNA expression, from the unripe to the favourable cervical
      state during labour, may indicate a role of eNOS and supports the role of NO in
      the cervical ripening process. All the three synthases were identified by
      immunohistochemistry in all the groups of study.

PMID- 16092968
TI  - Relationship between sialic acid and metabolic variables in Indian type 2
      diabetic patients.
AB  - BACKGROUND: Plasma sialic acid is a marker of the acute phase response. Objective
      is to study the relationship between sialic acid relationship with metabolic
      variables in Indian type 2 diabetes with and without microvascular complications.
      RESEARCH DESIGN AND METHODS: Fasting Venous blood samples were taken from 200
      subjects of which 50 were of diabetes mellitus (DM) and nephropathy patients, 50
      patients with type 2 diabetes and retinopathy, 50 patients with type 2 diabetes
      without any complications and 50 healthy individuals without diabetes. The Indian
      subject's aged 15-60 years with type 2 diabetes were recruited for the study.
      Simultaneously urine samples were also collected from each of the subjects. All
      the blood samples were analyzed for total cholesterol, triglyceride (TG), low
      density lipoprotein (LDL), high-density lipoprotein (HDL), fasting and
      postprandial glucose on fully automated analyzer. Serum and urine sialic acid
      along with microalbumin levels were also estimated. RESULTS: There was a
      significantly increasing trend of plasma and urine sialic acid with severity of
      nephropathy (P < 0.001) and with degree of urinary albumin excretion (P < 0.001).
      Serum sialic acid correlated with increasing serum creatinine concentration (P <
      0.001). Elevated serum sialic acid concentrations were also associated with
      several risk factors for diabetic vascular disease: diabetes duration, HbA1c,
      serum triglyceride and cholesterol concentrations, waist-to-hip ratio and
      hypertension. Significant correlations were found between sialic acid
      concentration and cardiovascular risk factors like LDL and TG in the diabetic
      subjects. CONCLUSION: The main finding of this study is that elevated serum and
      urinary sialic acid and microalbumin concentrations were strongly related to the
      presence of microvascular complications like diabetic nephropathy and retinopathy
      and cardiovascular risk factors in Indian type 2 diabetic subjects. Further study
      of acute-phase response markers and mediators as indicators or predictors of
      diabetic microvascular complications is therefore justified.

PMID- 16092969
TI  - Inequalities in neighbourhood socioeconomic characteristics: potential evidence
      base for neighbourhood health planning.
AB  - BACKGROUND: Population health planning aims to improve the health of the entire
      population and to reduce health inequities among population groups. Socioeconomic
      factors are increasingly being recognized as major determinants of many aspects
      of health and causes of health inequities. Knowledge of socioeconomic
      characteristics of neighbourhoods is necessary to identify their unique health
      needs and enhance identification of socioeconomically disadvantaged populations.
      Careful integration of this knowledge into health planning activities is
      necessary to ensure that health planning and service provision are tailored to
      unique neighbourhood population health needs. In this study, we identify unique
      neighbourhood socioeconomic characteristics and classify the neighbourhoods based
      on these characteristics. Principal components analysis (PCA) of 18 socioeconomic
      variables was used to identify the principal components explaining most of the
      variation in socioeconomic characteristics across the neighbourhoods. Cluster
      analysis was used to classify neighbourhoods based on their socioeconomic
      characteristics. RESULTS: Results of the PCA and cluster analysis were similar
      but the latter were more objective and easier to interpret. Five neighbourhood
      types with distinguishing socioeconomic and demographic characteristics were
      identified. The methodology provides a more complete picture of the neighbourhood
      socioeconomic characteristics than when a single variable (e.g. income) is used
      to classify neighbourhoods. CONCLUSION: Cluster analysis is useful for generating
      neighbourhood population socioeconomic and demographic characteristics that can
      be useful in guiding neighbourhood health planning and service provision. This
      study is the first of a series of studies designed to investigate health
      inequalities at the neighbourhood level with a view to providing evidence-base
      for health planners, service providers and policy makers to help address health
      inequity issues at the neighbourhood level. Subsequent studies will investigate
      inequalities in health outcomes both within and across the neighbourhood types
      identified in the current study.

PMID- 16092970
TI  - Efficient trapping of HIV-1 envelope protein by hetero-oligomerization with an N
      helix chimera.
AB  - BACKGROUND: The N-heptad repeat region of the HIV-1 Transmembrane Envelope
      protein is a trimerization domain that forms part of a "six helix bundle" crucial
      to Envelope-mediated membrane fusion. N-heptad repeat peptides have been used as
      extracellular reagents to inhibit virus fusion. RESULTS: When expressed
      intracellularly with wild-type HIV-1 Envelope protein, the N-heptad repeat domain
      efficiently hetero-oligomerized with Envelope and trapped it in the endoplasmic
      reticulum or early Golgi, as indicated by lack of transport to the cell surface,
      absent proteolytic processing, and aberrant glycosylation. CONCLUSION: Post
      translational processing of HIV Envelope is very sensitive to an agent that binds
      to the N-heptad repeat during synthesis, suggesting that it might be possible to
      modify drugs that bind to this region to have transport-blocking properties.

PMID- 16092972
TI  - The potential impact of the next influenza pandemic on a national primary care
      medical workforce.
AB  - BACKGROUND: Another influenza pandemic is all but inevitable. We estimated its
      potential impact on the primary care medical workforce in New Zealand, so that
      planning could mitigate the disruption from the pandemic and similar challenges.
      METHODS: The model in the "FluAid" software (Centers for Disease Control and
      Prevention, CDC, Atlanta) was applied to the New Zealand primary care medical
      workforce (i.e., general practitioners). RESULTS: At its peak (week 4) the
      pandemic would lead to 1.2% to 2.7% loss of medical work time, using conservative
      baseline assumptions. Most workdays (88%) would be lost due to illness, followed
      by hospitalisation (8%), and then premature death (4%). Inputs for a "more
      severe" scenario included greater health effects and time spent caring for sick
      relatives. For this scenario, 9% of medical workdays would be lost in the peak
      week, and 3% over a more compressed six-week period of the first pandemic wave.
      As with the base case, most (64%) of lost workdays would be due to illness,
      followed by caring for others (31%), hospitalisation (4%), and then premature
      death (1%). CONCLUSION: Preparedness planning for future influenza pandemics must
      consider the impact on this medical workforce and incorporate strategies to
      minimise this impact, including infection control measures, well-designed
      protocols, and improved health sector surge capacity.

PMID- 16092971
TI  - Interferon-gamma alters the phagocytic activity of the mouse trophoblast.
AB  - Interferon-gamma (IFN-gamma) mediates diverse functions in bone marrow-derived
      phagocytes, including phagocytosis and microbe destruction. This cytokine has
      also been detected at implantation sites under both physiological and
      pathological conditions in many different species. At these particular sites, the
      outermost embryonic cell layer in close contact with the maternal tissues, the
      trophoblast exhibits intense phagocytic activity. To determine whether IFN-gamma
      affects phagocytosis of mouse-trophoblast cells, ectoplacental cone-derived
      trophoblast was cultured and evaluated for erythrophagocytosis. Phagocytic
      activity was monitored ultrastructurally and expressed as percentage of
      phagocytic trophoblast in total trophoblast cells. Conditioned medium from
      concanavalin-A-stimulated spleen cells significantly enhanced trophoblast
      phagocytosis. This effect was blocked by pre-incubation with an anti-IFN-gamma
      neutralizing antibody. Introduction of mouse recombinant IFN-gamma (mrIFN-gamma)
      to cultures did not increase cell death, but augmented the percentage of
      phagocytic cells in a dose-dependent manner. Ectoplacental cones from mice
      deficient for IFN-gamma receptor alpha-chain showed a significant decrease of the
      phagocytosis, even under mrIFN-gamma stimulation, suggesting that IFN-gamma
      induced phagocytosis are receptor-mediated. Reverse transcriptase-PCR analyses
      confirmed the presence of mRNA for IFN-gamma receptor alpha and beta-chains in
      trophoblast cells and detected a significant increase in the mRNA levels of IFN
      gamma receptor beta-chain, mainly, when cultured cells were exposed to IFN-gamma.
      Immunohistochemistry and Western blot analyses also revealed protein expression
      of the IFN-gamma receptor alpha-chain. These results suggest that IFN-gamma may
      participate in the phagocytic activation of the mouse trophoblast, albeit the
      exact mechanism was not hereby elucidated. Protective and/or nutritional fetal
      benefit may result from this physiological response. In addition, our data also
      shed some light on the understanding of trophoblast tolerance to
      inflammatory/immune cytokines during normal gestation.

PMID- 16092973
TI  - Suicidal tendencies and attitude towards freedom to choose suicide among
      Lithuanian schoolchildren: results from three cross-sectional studies in 1994,
      1998, and 2002.
AB  - BACKGROUND: Suicidal behaviour is increasingly becoming a phenomenon associated
      with young people and an important public health issue in Lithuania. However,
      there are very few studies evaluating impact of young peoples' attitudes towards
      suicide to their suicidal behaviour. A better understanding of the relations
      among the variables associated with suicidal ideation and threats in the normal
      population of adolescents may eventually result in a better understanding of the
      more serious forms of adolescent suicidal behaviour. The aim of the present study
      was to evaluate prevalence of suicidal tendencies among Lithuanian schoolchildren
      and to estimate its association with an attitude towards suicide in 1994-2002.
      METHODS: Three country representative samples of schoolchildren, aged 11, 13 and
      15, were surveyed in 1994 (n = 5,428), 1998 (n = 4,513), and 2002 (n = 5,645)
      anonymously in conformity with the methodology of the World Health Organization
      Cross--National study on Health Behaviour in School-aged Children (HBSC).
      RESULTS: About one third of respondents reported about suicidal ideation, plans
      or attempts to commit suicide. In the study period of eight years, the percentage
      of adolescents who reported sometime suicidal ideation decreased but the
      percentage of adolescents who declared serious suicidal behaviour remained on the
      same high level (8.1%, 9.8% and 8.4% correspondingly in 1994, 1998 and 2002).
      Moreover, the number of suicidal attempts changed from 1.0% in 1994 to 1.8% in
      the year 1998 and to 1,7% in the year 2002. The schoolchildren's attitude towards
      suicide became more agreeable: 36.6%, 41.9% and 62.5% of respondents,
      correspondingly in 1994, 1998 and 2002, answered that they agree with a person's
      freedom to make a choice between life and suicide. A multiple logistic regression
      analysis with low level of suicidality and high level of suicidality versus non
      suicidal behaviour as dependent variables for gender, age, year of the survey and
      attitude towards freedom to choose suicide as independent variables approved a
      significant association between studied covariates over the entire study period.
      CONCLUSION: Suicidal tendencies are quite frequent among Lithuanian adolescents.
      An increasing number of schoolchildren are expressing an agreeable attitude
      towards suicide. The approving attitude towards suicide among adolescents
      correlates with suicidal ideation and behaviour.

PMID- 16092974
TI  - [Further investigations on the mechanisms in drug treatment of liver fibrosis].

PMID- 16092975
TI  - [Proteomic analysis of proliferation and apoptosis in carbon tetrachloride
      induced rat liver fibrosis].
AB  - OBJECTIVE: To study the proliferation and apoptosis in carbon tetrachloride
      induced rat liver fibrosis. METHODS: Wistar rats were injected subcutaneously
      with 40% CCl4-olive oil twice weekly for 12 weeks. Liver tissues were obtained at
      the end of 4, 8, 12 and 16 weeks for histological examination, hydroxyproline
      (Hyp) assay and proteomic analysis. After two dimension electrophoresis (2-DE),
      the silver stained gels were analyzed with PDQUEST 2-DE. More than 30
      differentially expressed proteins were identified by MALDI-TOF-MS. RESULTS: The
      degree of collagen deposition and hydroxyproline content of the fibrotic livers
      increased continuously during the 12 weeks of CCl4 administration, peaked at the
      end of week 12 (P < 0.05) and declined significantly at week 16 (P < 0.05).
      Significant differences were observed in two parameters at each time point
      between the control and the model group. Meanwhile, dramatic change of hepatic
      proteome in the model group rats was also seen. Differentially expressed proteins
      identified by MALDI-TOF-MS were categorized as proliferation-related
      proteins/enzymes (proliferating cell nuclear antigen p120, p40 and cyclin F
      ubiquitin-conjugating enzyme 7 UBC7), and apoptosis-related proteins, mainly
      caspase-12 which was absent in the control rats. CONCLUSION: Proliferation and
      apoptosis related proteins are expressed dynamically in different stages of rat
      liver fibrosis induced by CCl4.

PMID- 16092976
TI  - [Aldosterone stimulating PDGF-B expression in HSC via activation of EGR-1].
AB  - OBJECTIVE: It is known that intrahepatic renin-angiotensin-aldosterone system
      (RAAS) plays a key role in liver fibrogenesis. Aldosterone (Aldo), the principal
      effector molecule of the RAAS, exerts local effects on cell growth and
      fibrogenesis. However, the signal transduction mechanisms underlying the effects
      of Aldo on hepatic fibrogenesis remain to be fully elucidated. The present study
      aims to investigate the signal transduction mechanism underlying the effects of
      Aldo on extracellular signal-regulated kinase 1/2 (ERK1/2), early growth response
      1 (EGR-1) and on the platelet-derived growth factor-B (PDGF-B). METHODS: In
      vitro, hepatic stellate cell (HSC)-T6 cell line was treated with Aldo for 10 min,
      0.5 h, 1 h, 2 h and 3 h. Protein expression of phospho-p42/44 was detected by
      Western blot. In addition, HSC-T6 were preincubated for 1 h or not at all with
      U0126 (an inhibitor of the MAPK/ERK kinase), and antioxidant-N-acetylcysteine
      (NAC) prior to exposure to Aldo for the indicated times. Protein expressions of
      phospho-p42/44 and PDGF-B were measured by Western blot. DNA biding activity of
      EGR-1 was analyzed by electrophoretic gel mobility shift assay (EMSA). By means
      of immunohistochemistry, expression of PDGF-B was detected. RESULTS: Aldo induced
      phospho-p42/44 expression could be abrogated by U0126; NAC did not inhibit
      phospho-p42/44 expression. Gel shift study showed that stimulation of HSC by Aldo
      markedly increased the EGR-1 DNA binding activity, which was abrogated by U0126,
      reaching a maximum at 60 minutes, and then declined progressively. NAC did not
      reduce the EGR-1 activity. Aldo increased the PDGF-B protein level in HSC, which
      was not attenuated by NAC and U0126. CONCLUSIONS: Stimulation of HSC by Aldo
      results in activation of EGR-1 via ERK1/2 pathway, leading to up-regulation of
      PDGF-B expression.

PMID- 16092977
TI  - [Inhibition of proliferation of hepatic stellate cells by taurine is mediated via
      regulating cell cycle proteins].
AB  - OBJECTIVE: To explore the possible mechanism(s) of taurine-inhibiting the
      proliferation of hepatic stellate cells (HSC), this study investigated the effect
      of taurine on the HSC cell cycle and its regulatory protein expression. METHODS:
      Cell proliferation was assessed by MTT assay. Cell cycle was analyzed by flow
      cytometry. Cell cycle regulatory protein Cyclin D1 and P21waf1 expression were
      determined by immunocytochemistry and image-analysis system, and real-time
      quantitative PCR. RESULTS: HSC proliferation was markedly inhibited when HSC were
      treated with taurine at concentrations of 5, 10, 20, 30, 40 and 50 mmol/L for 48
      hours, and the inhibition rates were 6.7%, 14.4%, 23.3%, 32.2%, 36.7% and 45.6%
      respectively (P < 0.05-0.01). In the flow cytometry analysis, it was found that
      taurine could block HSC in the G0/G1 phase from entering the S phase, resulting
      in more cells in the G0/G1 phase and fewer in the S phase. The percentage of the
      cells in the G0/G1 phase and the S phase at the dosage of 40 mmol/L were 68.2%+/
      1.4% and 26.2+/-1.3% respectively, which was significantly different in
      comparison to the controls (56.2%+/-1.7% and 38.5%+/-0.8% respectively, P <
      0.01). HSC expressed cyclin D1 and P21waf1. Taurine inhibited cyclin D1
      expression and induced P21waf1 expression. The cyclin D1 protein and mRNA in the
      HSC treated with 40 mmol/L taurine were significantly reduced compared with the
      controls [protein (optical density value): 0.13+/-0.02 versus 0.18+/-0.02, P <
      0.01; mRNA: 5776.7+/-3345.0 versus 18,400.6+/-1374.8 copies/10(6) GAPDH, P <
      0.01]; and the P21waf1 protein and mRNA were markedly increased compared with the
      controls [protein (optical density value): 0.19+/-0.02 versus 0.14+/-0.01, P <
      0.01; mRNA: 44,866.7+/-3910.7 versus 16,933.3+/-960.9 copies/10(6) GAPDH, P less
      than 0.05]. CONCLUSIONS: Cyclin D1 and P21waf1 were cell cycle regulatory
      proteins in HSC, and taurine can inhibit the HSC cyclin D1 expression and
      stimulate P21waf1 expression, facilitate arresting cells in G0/G1 phase, and
      suppress cell proliferation.

PMID- 16092978
TI  - [Study on the inhibitive effect of Astragalus Injection solution on hepatic
      fibrosis in rats].
AB  - OBJECTIVE: To investigate the effect of Astragalus Injection solution on rat
      hepatic stellate cells (HSC) and hepatic fibrosis. METHODS: HSCs of rats were
      incubated with various concentrations of Astragalus Injection solution (0 mg/ml,
      25 mg/ml, 50 mg/ml, 100 mg/ml, 200 mg/ml, 400 mg/ml) for 24, 48 and 72 hours.
      Cell proliferation was detected with 3-(4, 5-dimethylthiazol-2-yl)-2,5
      diphennyltetrazolium bromide (MTT) colorimetric assay. Cell cycle was detected
      with flow cytometry. Cell apoptosis was detected with acridine orange/ethidium
      bromide (AO/EB) fluorescent staining and flow cytometry. In vivo, rats were
      randomly allocated into a normal control group, a model control group and an
      Astragalus Injection group. Astragalus Injection (800 mg.kg-1.d-1) was
      administered to rats of the Astragalus Injection group. Rats of the model control
      group received saline. Serum concentrations of hyaluronic acid (HA) and laminin
      (LN), hepatic tissue activity of superoxide dismutase (SOD), and hepatic tissue
      contents of malondialdehyde (MDA) were measured in these groups at 8 weeks.
      Hepatic tissue expression of LN was assessed by using immunohistochemistry. The
      pathological changes of hepatic tissues were examined by hematoxylin-eosin (HE)
      and van Gieson (VG) staining of their histological slides. RESULTS: In vitro,
      compared with the 0 mg/ml group, the proliferation of HSCs in other concentration
      groups was significantly inhibited by Astragalus Injection solution in a dose and
      time dependent manner, the cell proliferation cycle of HSCs was blocked in the G2
      M phase, there was no apoptosis of HSCs in AO/EB fluorescent staining and flow
      cytometry. In vivo, compared with rats of the model control group, the rats of
      the Astragalus Injection solution treated group had remarkably decreased serum HA
      and LN levels (114.3+/-25.6) microg/L vs (85.6+/-37.3) microg/L and (78.8+/-11.7)
      microg/L vs (66.8+/-17.6) microg/L, P < 0.05, and liver MDA level (3.7+/-0.4)
      micromol/g protein vs (2.4+/-0.2) micromol/g protein, P < 0.01, but had increased
      activity of liver SOD (49.6+/-5.7) NU/mg protein vs (75.9+/-5.9) NU/mg protein, P
      < 0.01. Microscopic studies revealed that the livers of rats receiving Astragalus
      Injection solution showed decreases in fibrosis and in expression of LN.
      CONCLUSIONS: Astragalus Injection solution has an inhibitive effect on
      experimental hepatic fibrogenesis. The mechanisms of its effects might possibly
      be associated with its antioxidant activity, expression of decreasing LN and its
      inhibition of HSCs proliferation.

PMID- 16092979
TI  - [Study of the down-regulating effect of hepatitis C virus NS5A protein on NACA
      promoter].
AB  - OBJECTIVE: To investigate the effect of hepatitis C virus (HCV) non-structure
      protein NS5A on the activity of calcium-regulating protein alpha subunit of
      nascent polypeptide-associated complex (NACA) promoter. METHODS: HepG2 cell
      plasmid pCAT3-NACA, containing NACA promoter, was transfected alone or
      cotransfected with pcDNA3.1(-)-NS5A, and chloramphenicol acetyl transferase (CAT)
      enzyme activity was assayed by enzyme-linked immunoassay (ELISA). RESULTS: The
      CAT activity in the pcDNA3.1(-)-NS5A cotransfection group was 20.7% of the CAT
      activity in the pCAT3-NACA group. CONCLUSION: HCV non-structural protein NS5A has
      a down-regulating effect on the promoter of NACA gene.

PMID- 16092980
TI  - [Fusion of TGF-beta 1 antigenic determinant and HBV core antigen as an anti-TGF
      beta 1 vaccine].
AB  - OBJECTIVES: To examine the expression and purification of the TGFbeta1 vaccine
      from prokaryotic expression system and to determine the antigenicity of the
      fusion protein of recombinant vector pET28a/ HBcAg1-71-TGFbeta132-HBcAg89-144.
      METHODS: The reconstructed vector pGEMEX-1/CTC was subcloned to pET28a and
      transformed into E. coli BL21 (DE3). The recombinant 6xHis- HBcAg1-71- TGFbeta132
      HBcAg89-144 was to be expressed after induction by IPTG and purified with Ni-NTA
      His affinity chromatography. The detection of the formation of core-like
      particles was done under an electron microscope and of their antigenity by using
      ELISA and Western blot. RESULTS: A 2.46 x 10(4) protein was obtained by
      optimizing the conditions for both expression and purification. The protein had
      the TGFbeta1 antigenicity but not a HBc antigenity and the formed core-like
      particles were bigger than natural core particles. CONCLUSION: The recombinant
      fusion protein in the prokaryotic expressed system can be used as an anti
      TGFbeta1 vaccine to inhibit hepatic fibrosis.

PMID- 16092981
TI  - [A single factor analysis of the prognosis of 301 hepatitis failure cases and a
      study of a scoring system on their prognostic assessment].
AB  - OBJECTIVES: To analyze the factors related to prognosis of hepatitis failure and
      to determine the factors which significantly affect it, and to build a scoring
      system for assessment of the prognosis of hepatitis failure and also to examine
      its efficacy for clinical use. METHODS: Clinical data from 301 patients were
      analyzed retrospectively. The correlated degree between those single factors and
      prognosis of hepatitis failure was explored by logistic regression analysis.
      Independent risk factors of prognosis and those correlated coefficients, which
      were from logistic regression analysis, were used to build a scoring system. This
      system was used in analyzing the clinical data of 275 patients to examine its
      efficacy of the prognostic assessment. RESULTS: The factors that significantly
      affected the prognosis of hepatitis failure included age, clinical typing,
      hepatic coma, total bilirubin, and others (P < 0.01). Some factors, including
      PTA, blood urea, sodium and hepatic coma, were independent risk factors of
      prognosis. The scoring system built gave different scores between the effective
      treatment group and ineffective treatment group with statistical significance (P
      < 0.01). When the score was less than 40, the probability of a recovery was
      76.9%; when the score was 40 to 80, the probability of a recovery was only 12.5%.
      When the score was more than 80, the probability of a recovery dropped to 0%.
      CONCLUSIONS: The factors, including PTA, blood urea and sodium and hepatic coma,
      are important in building a scoring system to assess the prognosis of hepatitis
      failure. The scoring system we built is very effective in evaluating the
      prognosis of hepatitis failure.

PMID- 16092982
TI  - [IgM to recombinant antigen E2 of HEV envelope protein is a sensitive and
      specific serological marker in diagnosis of acute hepatitis E].
AB  - OBJECTIVES: To evaluate the sensitivity and specificity of IgM to recombinant
      antigen E2 of HEV envelope protein in the diagnosis of acute sporadic hepatitis
      E. METHODS: anti-E2 IgM was detected in sera samples from 176 cases of acute
      sporadic hepatitis E and 191 cases of acute non A-E hepatitis by ELISA and was
      compared with HEV IgM detected by some domestic and Genelabs (GL) kits. HEV RNA
      was also detected in sera positive for anti-E2 IgM. Logistic regression was used
      to analyze factors associated with the detection of anti-E2 IgM and HEV RNA.
      RESULTS: Anti-E2 IgM was found in 68.75% of the serum samples from the 176
      patients of acute hepatitis E and the positive rate of HEV IgM detection by
      domestic kits was 56.25% (chi2 IgM = 6.49, P < 0.05). There were 37 (19.37%) anti
      E2 IgM positive cases in those 191 sera of the acute non A-E hepatitis, out of
      which 11 cases were also detected as positive by the GL kit. Of the 158 anti-E2
      IgM positive sera, HEV RNA was found in 81 (51.27%), among which 57.02% was
      positive in acute hepatitis E and 32.43% in acute non A-E hepatitis. No HEV RNA
      was found in the anti-E2 IgM negative sera from the cases of acute hepatitis E.
      By logistic regression analysis, no variance relative to the detection of anti-E2
      IgM was found with the time interval from onset to hospitalization, age, levels
      of bilirubin, ALT and AST of the serum. Only the level of serum ALT was found
      being significantly associated with the detection of HEV RNA (P = 0.024).
      CONCLUSIONS: (1) anti-E2 IgM is a sensitive and specific serological maker for
      diagnosing an acute infection of HEV. (2) HEV is still the pathogen of some cases
      diagnosed clinically as non-A-E hepatitis. (3) Persistent HEV viremia is possibly
      an important factor influencing the severity of acute hepatitis E.

PMID- 16092983
TI  - [Detection of mutants of the "a" determinant region of hepatitis B surface
      antigen S gene among Wuhan childhood patients].
AB  - OBJECTIVE: To investigate whether the presence of HBV mutant in vaccinees simply
      reflects the prevalence of HBV mutant in a specific geographic area or is indeed
      due to the immune pressure induced by vaccination. METHODS: HBV S genes were
      amplified by using polymerase chain reaction (PCR) and DNA sequence analysis of
      the "a" determinant was performed on sera from 30 childhood patients with
      immunoprophylaxis and 30 patients without vaccinations. RESULTS: Mutations of the
      "a" determinant were detected in 8 of the 60 patients. They were all of the adw
      subtype. The prevalence of amino acid substitutions as detected by direct
      sequencing was higher in those fully-vaccinated than of those not vaccinated. In
      all 8 vaccinated and also with detectable mutants, the mean age was older than
      the other vaccinated children. CONCLUSION: The prevalence of mutants is related
      to HBV subtypes and genotypes. Universal vaccination has accelerated an
      accumulation of HBsAg "a" determinant mutants with amino acid changes critical
      for immune escape in vaccinated children who became carriers. This suggests that
      new vaccination strategies should be considered.

PMID- 16092984
TI  - [A study of the changes of hepatic gene expression in the process of nonalcoholic
      fatty liver disease development using U230A oligonucleotide microarray].
AB  - OBJECTIVES: To explore the changes of hepatic gene expression during the course
      of nonalcoholic fatty liver disease (NAFLD) development in rats. METHODS: A rat
      model of NAFLD was developed by feeding the animals a high-fat diet for 24 weeks.
      Liver tissues of the model rats and the control rats were analyzed at different
      time points using rat U230A (Affymetrix GeneChip), which covers 15650 genes.
      RESULTS: Compared with the control rats, the number of genes expressed
      differently in the model group rats at 4 and 8 weeks was 426 and 540. The up
      regulated genes among them were intracellular phosphorylase genes, metabolic
      enzyme genes, fatty acid binding protein genes, cytochrome P450 genes, cellular
      transcription and differentiation genes. The down-regulated genes were ionic
      channel genes, hormone receptor genes, and cytoskeleton genes. At the 12th week,
      the number of the genes expressed differently was 501, in which 352 were up
      regulated genes, including genes related to inflammation and apoptosis such as
      interleukin and Toll-like receptor 4. At the 16th week, the number of the
      differently expressed genes was 665, with 430 up-regulated, such as those related
      to the inflammation and apoptosis genes and collagen I and fibrosis genes,
      however cell regeneration genes were down-regulated. At the 24th week the number
      was 663, of which fibroblast growth factor, transforming growth factor and
      insulin-like growth factor genes were up-regulated. Of all the differently
      expressed genes, the number of up-regulated genes was 128, including 10 lipogenic
      genes, 46 metabolic genes, 15 inflammation genes, 10 apoptosis genes, and 16
      fibrosis genes; and the down-regulated genes were 52, including 6 hormone
      receptor genes, 5 cell regeneration genes and 11 electron transport genes.
      CONCLUSION: The changes of the hepatic gene expression of rats fed a fat-rich
      diet are related to the duration of the feeding, and are correlated with their
      histopathology in the livers.

PMID- 16092985
TI  - [A preliminary study on the serum HBsAg level in patients with chronic hepatitis
      B and hepatitis cirrhosis during lamivudine therapy].

PMID- 16092986
TI  - [Diagnosis and evaluation of hepatic fibrosis].

PMID- 16092987
TI  - [A case report of hepatic myelopathy with abnormal brain MR imaging in the globus
      pallidus].

PMID- 16092988
TI  - [Considerations about suitable patients and suitable time for treating liver
      fibrosis].

PMID- 16092989
TI  - [Therapy for liver fibrosis].

PMID- 16092990
TI  - [Damage of the expression of NF-kappa B, myeloperoxidase and tissue factor in
      liver tissue and disorder of blood coagulation following liver ischemia
      reperfusion injury in rats].

PMID- 16092991
TI  - [Effects of tetrandrine on transmembrane signaling in rat hepatic stellate
      cells].

PMID- 16092992
TI  - [Effects of isosorbide-5-mononitrate on esophageal manometry of cirrhotic
      patients with esophageal varices].

PMID- 16092993
TI  - [A study on quasispecies of HBV precore in liver tissue and serum in fulminant
      hepatitis B patients].

PMID- 16092994
TI  - [Detection rate of primary sclerosing cholangitis in 160 cases of ulcerative
      colitis].

PMID- 16092995
TI  - [Influence of KAI1 gene on the growth and invasion of human hepatocellular
      carcinoma MHCC97-H cells].

PMID- 16092996
TI  - [Identification of a natural opioid peptide Leu-Val-Val-hemorphin-6 in
      hepatocarcinoma cells of a patient by LC-MS].

PMID- 16092997
TI  - [The effect and mechanism of Nocardia rubra cell wall skeleton treatment on mice
      with acute hepatitis induced by CCl4].

PMID- 16092998
TI  - [Effect of enalapril on caspase 3 in experimental liver fibrotic rats].

PMID- 16092999
TI  - [Tolerance limits of liver grafts with warm ischemia to cold preservation in
      swine].

PMID- 16093000
TI  - [Anti-hepatoma effect of arsenic trioxide on rat liver cancers induced by 2
      acetamidofluorene].

PMID- 16093001
TI  - [A report from the 12th Symposium on Viral Hepatitis and Liver Diseases].

PMID- 16093002
TI  - [A report from the 2nd Symposium on Fatty Liver Diseases].

PMID- 16093003
TI  - [Portal vein embolization, a review].

PMID- 16093004
TI  - [Analysis of the prognosis of severe hepatitis treated with molecular adsorbent
      recycling system (MARS) using MELD score].

PMID- 16093005
TI  - [NADPH oxidase in the pathogenesis of alcoholic liver diseases].

PMID- 16093006
TI  - [Endotoxin injury in alcoholic liver disease].

PMID- 16093007
TI  - [Gene therapy in liver diseases using adeno-associated virus as a vector].

PMID- 16093008
TI  - Are we closer to the prevention of HPV-related diseases?

PMID- 16093009
TI  - Overcoming barriers to HPV vaccine acceptance.

PMID- 16093010
TI  - Evaluating the impact of HPV-related diseases: cervical cancer and genital warts.

PMID- 16093011
TI  - Random regression analyses using B-splines to model growth of Australian Angus
      cattle.
AB  - Regression on the basis function of B-splines has been advocated as an
      alternative to orthogonal polynomials in random regression analyses. Basic theory
      of splines in mixed model analyses is reviewed, and estimates from analyses of
      weights of Australian Angus cattle from birth to 820 days of age are presented.
      Data comprised 84533 records on 20731 animals in 43 herds, with a high proportion
      of animals with 4 or more weights recorded. Changes in weights with age were
      modelled through B-splines of age at recording. A total of thirteen analyses,
      considering different combinations of linear, quadratic and cubic B-splines and
      up to six knots, were carried out. Results showed good agreement for all ages
      with many records, but fluctuated where data were sparse. On the whole, analyses
      using B-splines appeared more robust against "end-of-range" problems and yielded
      more consistent and accurate estimates of the first eigenfunctions than previous,
      polynomial analyses. A model fitting quadratic B-splines, with knots at 0, 200,
      400, 600 and 821 days and a total of 91 covariance components, appeared to be a
      good compromise between detailedness of the model, number of parameters to be
      estimated, plausibility of results, and fit, measured as residual mean square
      error.

PMID- 16093012
TI  - Correcting for bias in estimation of quantitative trait loci effects.
AB  - Estimates of quantitative trait loci (QTL) effects derived from complete genome
      scans are biased, if no assumptions are made about the distribution of QTL
      effects. Bias should be reduced if estimates are derived by maximum likelihood,
      with the QTL effects sampled from a known distribution. The parameters of the
      distributions of QTL effects for nine economic traits in dairy cattle were
      estimated from a daughter design analysis of the Israeli Holstein population
      including 490 marker-by-sire contrasts. A separate gamma distribution was derived
      for each trait. Estimates for both the alpha and beta parameters and their SE
      decreased as a function of heritability. The maximum likelihood estimates derived
      for the individual QTL effects using the gamma distributions for each trait were
      regressed relative to the least squares estimates, but the regression factor
      decreased as a function of the least squares estimate. On simulated data, the
      mean of least squares estimates for effects with nominal 1% significance was more
      than twice the simulated values, while the mean of the maximum likelihood
      estimates was slightly lower than the mean of the simulated values. The
      coefficient of determination for the maximum likelihood estimates was five-fold
      the corresponding value for the least squares estimates.

PMID- 16093013
TI  - The effect of fast created inbreeding on litter size and body weights in mice.
AB  - This study was designed to reveal any differences in effects of fast created
      versus total inbreeding on reproduction and body weights in mice. A line selected
      for large litter size for 124 generations (H) and a control line (K) maintained
      without selection for the same number of generations were crossed (HK) and used
      as a basis for the experiment. Within the HK cross, full sib, cousin or random
      mating were practised for two generations in order to create new inbreeding
      (IB(F)) at a fast rate. In the first generation of systematic mating, old
      inbreeding was regenerated in addition to creation of new inbreeding from the
      mating design giving total inbreeding (IB(T)). The number of pups born alive
      (NBA) and body weights of the animals were then analysed by a model including
      both IB(T) and IB(F). The IB(T) of the dam was in the present study found to
      reduce the mean NBA with -0.48 (+/-0.22) (p < 0.05) pups per 10% increase in the
      inbreeding coefficient, while the additional effect of IB(F) was -0.42 (+/-0.27).
      For the trait NBA per female mated, the effect of IB(T) was estimated to be -0.45
      (+/-0.29) per 10% increase in the inbreeding coefficient and the effect of IB(F)
      was -0.90 (+/-0.37) (p < 0.05) pups. In the present study, only small or non
      significant effects of IB(F) of the dam could be found on sex-ratio and body
      weights at three and six weeks of age in a population already adjusted for IB(T).

PMID- 16093014
TI  - A genome scan for quantitative trait loci affecting the Salmonella carrier-state
      in the chicken.
AB  - Selection for increased resistance to Salmonella colonisation and excretion could
      reduce the risk of foodborne Salmonella infection. In order to identify potential
      loci affecting resistance, differences in resistance were identified between the
      N and 6(1) inbred lines and two QTL research performed. In an F2 cross, the
      animals were inoculated at one week of age with Salmonella enteritidis and
      cloacal swabs were carried out 4 and 5 wk post inoculation (thereafter called
      CSW4F2 and CSW4F2) and caecal contamination (CAECF2) was assessed 1 week later.
      The animals from the (N x 6(1)) x N backcross were inoculated at six weeks of age
      with Salmonella typhimurium and cloacal swabs were studied from wk 1 to 4
      (thereafter called CSW1BC to CSW4BC). A total of 33 F2 and 46 backcross progeny
      were selectively genotyped for 103 and 135 microsatellite markers respectively.
      The analysis used least-squares-based and non-parametric interval mapping. Two
      genome-wise significant QTL were observed on Chromosome 1 for CSW2BC and on
      Chromosome 2 for CSW4F2, and four suggestive QTL for CSW5F2 on Chromosome 2, for
      CSW5F2 and CSW2BC on chromosome 5 and for CAECF2 on chromosome 16. These results
      suggest new regions of interest and the putative role of SAL1.

PMID- 16093015
TI  - A region on chicken chromosome 2 affects both egg white thinning and egg weight.
AB  - We describe the results from genetic dissection of a QTL region on chicken
      chromosome 2, shown to affect egg weight and quality in an earlier genome scan of
      an F2 intercross between two divergent egg layer lines. As the 90% confidence
      intervals for the detected QTL covered tens of centiMorgans, new analyses were
      needed. The datasets were re-analysed with denser marker intervals to
      characterise the QTL region. Analysis of a candidate gene from the original QTL
      region, vimentin, did not support its role in controlling egg white thinning.
      Even after reanalysis with additional seven markers in the QTL area, the 90%
      confidence intervals remained large or even increased, suggesting the presence of
      multiple linked QTL for the traits. A grid search fitting two QTL on chromosome 2
      for each trait suggested that there are two distinct QTL areas affecting egg
      white thinning in both production periods and egg weight in the late production
      period. The results indicate possible pleiotropic effects of some of the QTL on
      egg quality and egg weight. However, it was not possible to make a distinction
      between close linkage versus pleiotropic effects.

PMID- 16093016
TI  - Transformation of QTL genotypic effects to allelic effects.
AB  - The genotypic and allelic effect models are equivalent in terms of QTL detection
      in a simple additive model, but the QTL allelic model has the advantage of
      providing direct information for marker-assisted selection. However, the allelic
      matrix is four times as large as the genotypic IBD matrix, causing computational
      problems, especially in genome scans examining multiple positions. Transformation
      from genotypic to allelic effects, after estimating the genotypic effects with a
      smaller IBD matrix, can solve this problem. Although the validity of
      transformation from genotypic to allelic effects has been disputed, this work
      proves that transformation can successfully yield unique allelic effects when
      genotypic and allelic IBD matrixes exist.

PMID- 16093017
TI  - Arrogance.

PMID- 16093018
TI  - In search of Braveheart: unite the clans.

PMID- 16093019
TI  - Liver metastases: new approaches to a difficult challenge. Abstracts &
      commentary.

PMID- 16093020
TI  - Revascularization of myocardial infarction complicated by cardiogenic shock: an
      update. Abstracts & commentary.

PMID- 16093021
TI  - Laparoscopy and colon cancer. Abstracts & commentary.

PMID- 16093022
TI  - Current overview of pectus excavatum. Abstracts & commentary.

PMID- 16093023
TI  - Gastric cancer. Abstracts & commentary.

PMID- 16093024
TI  - Immunotherapy in colon cancer. Abstracts & commentary.

PMID- 16093026
TI  - Spinal cord injury: are there grounds for new hope? Abstracts & commentary.

PMID- 16093025
TI  - Firearm violence in the United States: an overview. Abstracts & commentary.

PMID- 16093027
TI  - Feeling the stress: perceptions of burnout among general surgery program
      directors.
AB  - PURPOSE: To document the types and levels of stress experienced by general
      surgery program directors as they fulfill their education and administrative
      responsibilities. METHODS: This study consisted of a 3-part survey that
      incorporated 2 established instruments to help determine the presence of burnout
      in program directors. A personal projects analysis was used to help identify the
      tasks most relevant to the role of program director as well as to evaluate their
      perceptions of these tasks. The Maslach Burnout Inventory (MBI) was used to
      measure the degree of burnout among program directors. Demographic data were
      gathered to develop a picture of the background of the program directors and how
      they spent their time. RESULTS: A total of 71.8% of program directors responded.
      Of all tasks, teaching received the highest ratings for importance, enjoyment,
      and control, as well as the lowest ratings for stress. Emotional exhaustion was
      the most notable aspect of burnout in program directors on the MBI. Program
      directors scoring high in burnout were younger, had been in their current
      position fewer years, and had fewer years overall as a program director.
      CONCLUSIONS: Burnout is more related to age and experience of program director
      than to features of the program itself.

PMID- 16093028
TI  - Introduction to the electronic media corner.

PMID- 16093029
TI  - Grand rounds in general surgery. Leg weakness in a middle-aged man with
      neurofibromatosis.

PMID- 16093030
TI  - Daring to take action: Charles McBurney and the evolution of the treatment of
      appendicitis.

PMID- 16093031
TI  - Muscle-splitting posterolateral thoracotomy: a novel technique.
AB  - PURPOSE: In an effort to decrease the morbidity of a standard posterolateral
      thoracotomy, numerous muscle-sparing approaches have been developed. However,
      these incisions have been limited by the need for excessive muscle retraction
      with resultant neuropraxia, difficulty with exposure, and postoperative wound
      seroma. We report our results of a novel muscle-splitting thoracotomy incision,
      which affords excellent exposure without significant morbidity. METHODS: We
      conducted a retrospective chart review of 37 consecutive patients who underwent
      "muscle-splitting" thoracotomy from June 1997 to June 1998. The technique, which
      involves a bidirectional spread of the latissimus dorsi and serratus anterior
      muscles, was performed by the same attending surgeon in all patients. RESULTS:
      There were 22 male and 15 female patients, aged 26 to 81 (mean, 58), with a body
      mass index ranging from 18 to 40 kg/m(2) (mean, 25 kg/m(2)). Procedures included
      lobectomy/segmentectomy (19), wedge resection (5), pneumonectomy (2), Belsey IV
      fundoplication (5), Ivor-Lewis esophagogastrectomy (1), T8/T9 thoracic exposure
      (1), and miscellaneous thoracic cases (4). Operative time ranged from 90 minutes
      to 420 minutes (mean, 176), which was comparable with similar procedures through
      a standard incision. No patients required conversion to a muscle-cutting
      thoracotomy. CONCLUSIONS: Our technique of muscle-splitting posterolateral
      thoracotomy appears to provide excellent operative exposure and to avoid problems
      seen with current muscle-sparing incisions. A prospective, randomized trial to
      compare this technique with a standard thoracotomy incision would be useful in
      determining its viability as an alternative thoracic approach.

PMID- 16093032
TI  - Editor's comment on muscle-splitting posterolateral thoracotomy: a novel
      technique.

PMID- 16093033
TI  - Repair of McBurney incisional hernias after open appendectomy.
AB  - Incisional herniation after appendectomy through a right lower quadrant muscle
      splitting (McBurney) incision is rare, occurring in less than 0.12% of operations
      for appendicitis. Primary repair of this form of hernia is particularly difficult
      as a result of the attenuated fascia created by the herniation. By using
      synthetic mesh, it is possible to effectively repair this type of hernia. Three
      cases of postoperative incisional herniation treated by different surgical
      approaches are reviewed.

PMID- 16093034
TI  - An introduction to the Resident Resource Corner: your own RRC.

PMID- 16093035
TI  - The physician assistant.

PMID- 16093036
TI  - Cardiothoracic postmyocardial infarction ventricular septal defect repair.
      Abstracts & commentary.

PMID- 16093037
TI  - Crohn's disease update. Abstracts & commentary.

PMID- 16093038
TI  - Hemorrhoid review. Abstracts & commentary.

PMID- 16093039
TI  - Geriatric nutrition and operative risk. Abstracts & commentary.

PMID- 16093040
TI  - Clinical resources: we need to monitor quality and costs. Abstracts & commentary.

PMID- 16093041
TI  - Inguinal hernias in children: an overview. Abstracts & commentary.

PMID- 16093042
TI  - Adjuvant therapy in rectal cancer. Abstracts & commentary.

PMID- 16093043
TI  - Brain injury. Abstracts & commentary.

PMID- 16093045
TI  - What should you do before you start to use your new computer, or once you've
      bought it, how do you keep from breaking it?

PMID- 16093044
TI  - Clinical research during surgery residency: the Chattanooga approach.
AB  - PURPOSE: The nontraditional clinical research rotation at the University of
      Tennessee College of Medicine-Chattanooga Unit is described and its efficacy
      evaluated by the number of peer-reviewed publications produced. METHODS: In 1988,
      a mandatory year of clinical research was added to the general surgery
      curriculum. The year is completed in 3 4-month rotations, 1 each during the PGY
      2, PGY-3, and PGY-4 years. Curriculum vitae of 31 graduates of the traditional 5
      year residency were evaluated for publications produced during residency and 1
      year beyond training. Comparison was made to 15 subjects; 8 were 6-year graduates
      and 7 were PGY-4, PGY-5, or PGY-6 residents having completed the research year.
      Statistical analysis used the Mann-Whitney U test for nonparametric data as well
      as an independent t test with significance set at 0.05. Publications were
      verified by a MEDLINE search. Six-year graduates also completed a questionnaire
      regarding their research experience. RESULTS: Graduates of the 5-year program
      completed an average of 0.94 publications during residency, whereas 6-year
      graduates completed an average of 2.67 publications (p < 0.001). Opinions varied
      regarding desire to pursue research and the benefit of the research year.
      CONCLUSIONS: Our results demonstrate that basic science research is not the only
      model; academic productivity can be improved with an additional year devoted to
      clinical research. Advantages to this nontraditional approach include decreased
      likelihood of decline of clinical skills and knowledge, ability to maintain long
      term projects, and a physical and mental break from a demanding clinical
      residency.

PMID- 16093046
TI  - Grand rounds in general surgery. Nonhealing skin ulcer in an octogenarian.

PMID- 16093047
TI  - Editor's comment.

PMID- 16093048
TI  - Medical ethics, moral reasoning, and medical education: introduction to a special
      section of student essays.

PMID- 16093049
TI  - Donor or vendor: the commodification of human eggs.

PMID- 16093050
TI  - HIV testing and its role in fighting the battle against AIDS: a comparison of
      mandatory, confidential, and anonymous testing.

PMID- 16093051
TI  - Human cloning: enhancing life at what cost?

PMID- 16093052
TI  - Practice guidelines: the physician's friend or foe?

PMID- 16093053
TI  - Prenatal care to future citizens.

PMID- 16093054
TI  - The consequences of multiple births and the regulation of assisted reproductive
      technologies.

PMID- 16093055
TI  - The ethics of mandatory versus voluntary HIV testing of pregnant women.

PMID- 16093056
TI  - Resident resource corner. Where do I look for a job?

PMID- 16093057
TI  - Electrosurgery 101.

PMID- 16093058
TI  - To drain or not to drain; still a valid question?

PMID- 16093059
TI  - Silicone breast implants--are they associated with connective tissue disease?:
      Part 5 of the 6-part series on current concepts in breast reconstruction.

PMID- 16093060
TI  - State of affairs of sentinel node biopsy for breast cancer.

PMID- 16093061
TI  - If it is right lower quadrant pain?

PMID- 16093063
TI  - Meckel's diverticulum: review and surgical management.

PMID- 16093062
TI  - The treatment of localized prostate cancer.

PMID- 16093064
TI  - Laparoscopic management of Meckel's diverticulum.

PMID- 16093065
TI  - Festschrift. David Sperling, MD.

PMID- 16093066
TI  - A brief history of thyroid surgery.

PMID- 16093067
TI  - Abdominal wall fascial disruption after blunt trauma: a case report and review of
      the literature.

PMID- 16093068
TI  - Minocycline-induced black thyroid gland: Medical curiosity or a marker for
      papillary cancer?
AB  - PURPOSE: Black pigmentation of the thyroid gland is a rare side effect of
      minocycline. METHODS: Only 26 cases, in addition to the 2 we present, have been
      reported in the literature. Eleven cases of thyroid carcinoma associated with
      black thyroid syndrome have been reported. CONCLUSIONS: The incidence of
      papillary cancer may be increased in thyroid glands stained by the minocycline
      pigment, which warrants an increased index of suspicion in patients who develop
      thyroid nodules and have previously been treated with minocycline.

PMID- 16093069
TI  - Reducing operative blood loss during hepatic surgery: from the middle ages to the
      space age.

PMID- 16093070
TI  - Surgical considerations for treatment of amiodarone-induced thyrotoxicosis.
AB  - PURPOSE: We present our experience with surgical management of amiodarone-induced
      thyrotoxicosis, including preoperative, intraoperative, and postoperative
      considerations. METHODS: Retrospective review of the medical records and the
      histological slides and a Medline search of amiodarone and thyroid gland.
      CONCLUSIONS: Amiodarone is a drug used to treat potentially lethal ventricular
      arrhythmia. One of the known side effects is thyroid dysfunction. In patients who
      cannot safely discontinue amiodarone or when medical therapy is ineffective in
      controlling thyrotoxicosis, thyroidectomy is the treatment of choice.

PMID- 16093071
TI  - The aberrant thyroid.

PMID- 16093072
TI  - Painful axillary mass in a middle-aged woman.

PMID- 16093073
TI  - Sigmoid colon diverticulosis adherent to mesh plug migration after open inguinal
      hernia repair.
AB  - PURPOSE: Tension-free hernia repair with polypropylene mesh plug and patch is
      currently the most popular technique for open inguinal hernioplasty. It is well
      tolerated by most patients with few complications. Despite these excellent
      results, late-onset complications may occur. METHODS: An 83-year-old man reported
      2 weeks of bloody stool. His medical history was significant for a left open
      inguinal herniorrhaphy with the mesh plug and patch technique. Barium enema
      revealed a stenotic segment in the sigmoid colon and multiple diverticulosis.
      Because a malignant lesion could not be ruled out, the patient underwent an
      operation. Laparotomy revealed an inflamed sigmoid colon with diverticulosis
      adherent to a hard tumor, which was mesh plug used for the previous open inguinal
      hernia repair. After mobilization of the adhesion between the mesh plug tumor and
      the sigmoid colon, sigmoidectomy was performed. The patient's postoperative
      course was uneventful. CONCLUSIONS: We reported a case of sigmoid colon
      diverticulosis adherent to mesh plug migration after open inguinal hernia repair.
      The potential risk of plug migration should be well understood by the surgeon. To
      avoid this risk completely, several methods have been proposed such as suturing
      the plug and patch together, or using an all-in-one design such as the Prolene
      Hernia System (Johnson and Johnson Co., Tokyo, Japan).

PMID- 16093074
TI  - Resident resource corner. A dying art.

PMID- 16093075
TI  - Digital photography.

PMID- 16093076
TI  - William Arthur Altemeier, MD: the life and times of a surgical legend.

PMID- 16093077
TI  - Yes: we made the Index Medicus!

PMID- 16093078
TI  - The epistle according to T. J.

PMID- 16093079
TI  - Evidence-based surgery.

PMID- 16093080
TI  - Hypothermia: the naked patient.

PMID- 16093081
TI  - PET scans: Is it time to install these in community hospitals?

PMID- 16093082
TI  - Physician assistants.

PMID- 16093083
TI  - Appropriate choices in breast reconstruction: Part 6 of the 6-part series on
      current concepts in breast reconstruction.

PMID- 16093084
TI  - Oxygen therapy in infection and injury.

PMID- 16093085
TI  - Solutions for central line infections: yes or no?

PMID- 16093086
TI  - Handheld devices, personal digital assistants, and palmtop devices; can you live
      with them or without them?

PMID- 16093087
TI  - Alfred Blalock.

PMID- 16093088
TI  - Your first employment agreement: what every surgery resident should know.

PMID- 16093089
TI  - The evolution and early experience with robot-assisted mitral valve surgery.
AB  - Cardiac surgeons, with a warranted enthusiasm, have embraced minimally invasive
      surgery. The acceleration of technological advances in optics, instrumentation,
      and cardiopulmonary bypass has allowed safe, effective, and efficient minimally
      invasive cardiac procedures. In this Technology Focus section, we review the
      evolution and early experience with robot-assisted mitral valve surgery. The
      articles of leading minimally invasive cardiac surgeons, both American and
      European, are reviewed to define the development toward cardiac robotic surgery.
      The current state of robotic mitral surgery is described.

PMID- 16093091
TI  - Morbidity and mortality conference: enhancing delivery of surgery residency
      curricula.
AB  - PURPOSE: To determine the exposure of surgical residents to educational subjects
      contained in the APDS 2000 Curriculum from a weekly Morbidity and Mortality (M&M)
      conference. METHODS: The departmental quality assurance data base was queried for
      content presented in a residency program's M&M conference. The presentation
      topics, the services involved, and the occurrence causation were all cataloged to
      assess the extent of material covered. The topic was logged if the case
      occurrence generated discussion beyond a superficial notation. An attending
      moderated the discussions, with resident and faculty interaction on causality
      determination. Imaging studies were available as appropriate to the case
      discussed. RESULTS: At least 95 discrete topics in 149 separate occurrences were
      covered in the weekly M&M conference in 1 academic year from July 1999 through
      June 2000. Common topics included wound infection (9), deep venous thrombosis
      (7), small bowel obstruction (5), and pulmonary embolus (4). Five topics were
      discussed 3 times, 23 were discussed twice, and 63 were discussed once. Although
      many occurrences had multiple causes, Pareto analysis of causation determined
      that nature of disease was prominent in 78 (52.4%), diagnostic difficulty in 31
      (20.8%), technical error in 27 (18.1%), and error in judgment in 13 (8.7%).
      Pareto analysis of the surgical domains addressed included trauma (37, 24.8%),
      general surgery (35, 23.5%), common issues independent of service (32, 21.5%),
      vascular (20, 13.5%), cardio thoracic (11, 7.4%), critical care (9, 6.1%), and
      all other services (5, 3.4%). CONCLUSIONS: A weekly M&M conference in a residency
      program provides broad exposure to material contained in the APDS 2000
      curriculum. A peer-reviewed M&M conference provides ongoing examination of common
      problems encountered in the delivery of surgical care. By so doing, it promotes
      interactive teaching of the most relevant surgical problems.

PMID- 16093092
TI  - The American College of Surgeons' role in surgical education of the future.

PMID- 16093093
TI  - Whatever happened to the General Surgery graduating class of 2001?
AB  - PURPOSE: Nationally approximately 20% of all categorical General Surgery (GS)
      residents do not complete their GS training. We ranked 57 applicants in the
      National Residency Match Program (NRMP) in 1996 and matched our final eighth
      candidate with slot 22. Although clinically stellar, 4 of these 8 residents (50%)
      opted to switch to different medical specialties. We pondered if other programs
      had difficulties with the 1996 applicant pool and hypothesized that perhaps
      higher ranked applicants have greater attrition rates. METHODS: Programs in which
      our ranked applicants matched were contacted and asked for feedback on trainee
      performance, research time, attrition, and future plans. RESULTS: Four applicants
      did not match in GS. Fifty-three surgical interns (46 men, 7 women) in 1996 are
      now 23 chief residents, 18 senior residents (16 did research time, 1 did an
      intensive care unit fellowship, and 1 required a year of remediation), and 12 non
      GS trainees (orthopedic surgery = 3, anesthesiology = 3, ENT = 1, family medicine
      = 1, internal medicine = 1, radiology = 1, pathology = 1, and Ph.D. researcher =
      1). Clinical performance was similar for both GS trainees and those who dropped
      out. Residents dropped out after the PG-1 year (n = 7), PGY-2 (n = 3), and 1 each
      after PGY-3 and PGY-4. Higher ranked applicants were no more likely to drop out
      than were lower ranked applicants. CONCLUSIONS: Of Mayo Clinic-Rochester-ranked
      GS categorical applicants in 1996, 23% dropped out of GS. Eleven of 12 dropouts
      selected a different field of medicine to finish their training. Attrition
      remains common and problematic both nationally and in individual programs.

PMID- 16093094
TI  - Joseph Colt Bloodgood: pioneer in surgical pathology.

PMID- 16093095
TI  - The dawn of a new specialty: preventive surgery.

PMID- 16093097
TI  - Delay in diagnosis of breast cancer: fact, fiction, or lawyer's folly?

PMID- 16093096
TI  - Coloanal anastomosis: maintaining sphincter function after resection of low
      rectal cancer.

PMID- 16093098
TI  - Esophageal cancer.

PMID- 16093099
TI  - Gastrojejunostomy in pancreatic cancer: is it worthwhile?

PMID- 16093100
TI  - Implant breast reconstruction in the irradiated cancer patient.

PMID- 16093102
TI  - Rectal cancer: Current issues.

PMID- 16093101
TI  - Photochemotherapy: more heat than light?

PMID- 16093103
TI  - Who was Sister Mary Joseph?

PMID- 16093104
TI  - Current diagnosis and treatment of cholecystitis.

PMID- 16093105
TI  - Laparoscopic cholecystectomy--technical considerations.

PMID- 16093106
TI  - Henri Albert Hartmann: labor and discipline.

PMID- 16093107
TI  - Basic aseptic technique for medical students: Identifying essential entry-level
      competencies.
AB  - PURPOSE: Medical students must be competent in basic aseptic technique (BAT) to
      function effectively in the operating room. However, a comprehensive literature
      review revealed a deficit of research in standardized BAT training for the
      operating room in medical school curricula. METHODS: A modified reactive Delphi
      technique was used to survey an expert panel of 100 surgical educators. A focus
      group provided initial responses to key questions, and the panel completed 2
      surveys. In the first survey, the panel identified elements for a BAT curriculum
      for the operating room. In the second survey, the panel received feedback from
      the first survey and was asked to respond in light of those results. RESULTS: An
      81% response rate was obtained from the first survey. A 74% response rate was
      obtained from the second survey. Seven of the 18 essential entry-level
      competencies (EELCs) identified were ranked as the most important. The top 5
      instructional strategies and the top 3 methods for evaluation were also selected.
      The panel identified the third-year curriculum as the preferred time of training
      and a nurse preceptor/educator as the preferred instructor. CONCLUSIONS: These
      results provide a minimum set of educational objectives that can be used to
      develop a standardized curriculum in BAT for the operating room for medical
      students.

PMID- 16093108
TI  - Laparoscopic cholecystectomy in pregnancy.
AB  - PURPOSE: Since the start of laparoscopic cholecystectomy, a debate about its use
      in the gravid patient has remained controversial. Concerns about the morbidity
      and mortality in the mother and fetus through all trimesters have been expressed.
      The objective of this retrospective review was to further evaluate the safety of
      laparoscopic cholecystectomy in the pregnant patient. METHODS: At Covenant Health
      Care-Cooper Campus and Harrison Campus in Saginaw, Michigan, 10 cholecystectomies
      in pregnant patients were performed from 1995 to April 1998. Eight of these
      patients were done with laparoscopy, and 2 were done through the open technique.
      RESULTS: No mortality or significant morbidity occurred in the laparoscopic
      group. However, the open group did have a fetal mortality. CONCLUSIONS: Our study
      showed that laparoscopic cholecystectomy can be performed safely in the pregnant
      patient in the first 2 trimesters. This is consistent with the findings in the
      current world literature.

PMID- 16093110
TI  - Resident resource corner. It was Sunday.

PMID- 16093109
TI  - The content and value of letters of recommendation in the resident candidate
      evaluative process.
AB  - PURPOSE: To determine the content and value of letters of recommendation (LOR) in
      the selection of residents for general surgery training. METHODS: During the 1999
      application process, we evaluated the source, content, and usefulness of 966 LOR
      for 288 viable applicants to our program. Each letter was reviewed to determine
      if the author had clinical contact with the student and whether the student's
      fund of knowledge, clinical achievements, psychomotor skills, and personal
      characteristics were described. The use and type of a "single word" summary was
      also noted. The program director then determined if the LOR was helpful in
      evaluating the student. PARTICIPANTS: All LOR in the application materials of
      candidates applying to the General Surgery Residency of the University of
      Arizona. RESULTS: All of the candidates submitted 3 LOR and 34% submitted 4. The
      average length was 13.7 (range, 4 to 36) sentences. Department chairs wrote LOR
      for 66% of the students, and these comprised 20% of the total LOR. Program
      directors, division chiefs, and clerkship directors wrote 16%, whereas other
      general surgery faculty contributed 40%. In 17% of the LOR, no evidence of direct
      clinical supervision could be found. Personal characteristics were described in
      89% of the letters, but reference to psychomotor skills occurred in only 27%. In
      58% of the LOR, a single adjective was used to describe the students; of these,
      "outstanding" (or equivalent) was used in 37% and "excellent" (or equivalent) was
      used in 38%. Meaningful comparison to student colleagues appeared in 11%. In our
      program director's opinion, 24% of the LOR were helpful in the evaluation
      process. The department chair's letters were helpful only 19% of the time.
      CONCLUSIONS: Letters of recommendation are imprecise indicators of student
      performance for resident candidate evaluation. A "standardized LOR" may help
      provide a consistent and more objective evaluative tool, and the APDS should
      consider its development for future selection processes.

PMID- 16093111
TI  - It was Sunday.

PMID- 16093112
TI  - Cutaneous T-cell lymphoma associated with ileostomy: management of uncommon
      stomal complication.
AB  - PURPOSE: Cutaneous T-cell lymphoma involvement of an ileostomy is a rare stomal
      complication. METHODS: We present the case of a 54-year-old man who presented
      with peristomal skin breakdown associated with fevers and chills. RESULTS: The
      stoma was taken down, and the surrounding skin debrided. A new ileostomy was
      created in left abdominal wall. Pathology specimens of the debrided skin,
      subcutaneous tissue, and stoma returned positive for cutaneous T-cell lymphoma.
      CONCLUSIONS: The medical treatment of the underlying T-cell lymphoma can give a
      good diagnosis when it is diagnosed early, but late-stage identification is less
      encouraging. The surgical treatment involves debridement and careful planning for
      ileostomy formation.

PMID- 16093113
TI  - Historical landmarks in operations on the colon--surgeons courageous.
AB  - PURPOSE: The nearly 300-year history of surgery of the colon is replete with
      creative daring among surgeons who conquered the challenges of operating on this
      highly contaminated organ, housed in the sacrosanct peritoneal cavity. METHODS:
      Alexis Littre's suggestion in 1710 that a colostomy may be successful in treating
      an infant with imperforate anus began an evolutionary process of extraperitoneal
      colostomy for obstructing carcinomas, and then, an intraperitoneal approach,
      which enhanced surgical evaluation of the tumor and optimal placement of the
      stoma. Reybard's introduction of sigmoid resection in 1823, followed by post
      Lister contributions of Mickulicz, Paul, Murphy, Miles, Hartmann, and other 19th-
      and early 20th-century surgeons, paved the way for current successes in colon
      surgery. RESULTS: The morbidity and mortality, which still accompanies surgery on
      the colon, often results from a failure of today's surgeon to apply those
      principles so meticulously documented by colon and rectum surgery historians.
      CONCLUSIONS: The individual, who performs a Miles abdominoperineal resection, a
      Hartmann procedure, or any other of the classic operations on the colon, gains
      much by studying the original philosophy and technique of these pioneers in the
      field.

PMID- 16093114
TI  - Horner's syndrome: a delayed complication after thoracostomy tube removal.
AB  - PURPOSE: Description of a complication from tube thoracostomy. METHODS: Case
      report from experience at an Air Force tertiary care hospital in a 50-year-old
      female smoker undergoing left upper lobectomy for lung cancer. RESULTS: Horner's
      syndrome resulted 18 hours after removal of an apical thoracostomy tube.
      CONCLUSIONS: Horner's syndrome caused by tube thoracostomy is a rare but real
      complication. One should avoid placing the tip of the tube in the medial thoracic
      apex with the intent of avoiding second-order sympathetic chain pathways. As
      evidenced by our patient with a delayed onset of presentation, malpositioned
      tubes should be repositioned before symptoms develop. Long-term prognosis is poor
      once Horner's syndrome develops.

PMID- 16093115
TI  - Simultaneous bilateral spontaneous pneumothorax: a case report.

PMID- 16093116
TI  - Surgical treatment of thymoma.
AB  - PURPOSE: A case report is presented of a 66-year-old white woman with a 3-month
      history of atypical chest pain and shortness of breath. METHODS: A lateral chest
      radiograph demonstrated an anterior mediastinal density. A subsequent computed
      tomography (CT) scan revealed a mass in the right anterolateral mediastinum. Fine
      needle aspiration (FNA) revealed tumor cells positive for cytokeratin and
      negative for leukocyte common antigen. RESULTS: The differential diagnosis at
      that time included thymoma versus thymic carcinoid. She underwent a median
      sternotomy with complete thymectomy. The pathology revealed a large thymoma with
      microinvasion into the surrounding adipose tissue. She had an uneventful
      postoperative course and later underwent adjuvant radiation therapy. CONCLUSIONS:
      Surgical treatment of thymoma is discussed, with emphasis on diagnosis and
      treatment. Although some patients may present with symptoms caused by involvement
      of surrounding structures, most thymomas are discovered incidentally on chest
      radiograph. Various diagnostic procedures can aid the surgeon in ruling out other
      neoplasms, such as lymphoma or germ cell tumors. Prognosis is not based on
      histology, but on the tumor's gross characteristics at operation. Benign tumors
      are noninvasive and encapsulated. All patients with potentially resectable
      lesions should undergo en-bloc excision. Radiation or chemotherapy should be
      instituted in more advanced tumors.

PMID- 16093117
TI  - Some tips on slide-making and electronic presentation.

PMID- 16093118
TI  - Is it possible to stay up-to-date after the residency?

PMID- 16093119
TI  - Residents seeking informed consent: Are they adequately knowledgeable?
AB  - PURPOSE: The purpose of this study was to determine the extent to which first
      year surgical residents are prepared to obtain informed consent from patients.
      The study was designed to answer the following research questions: 1) Are first
      year residents who are asked to obtain informed consent sufficiently
      knowledgeable about the risks, benefits, and alternatives of the procedures? 2)
      Can first-year residents accurately answer the questions patients may pose about
      these procedures? METHODS: First-year residents (n = 18) were asked to list the
      risks, benefits, and alternatives for open inguinal hernia repair, laparoscopic
      cholecystectomy, total thyroidectomy, esophagogastrectomy, and abdominal aortic
      aneurysm repair, assuming the procedures were elective on otherwise healthy
      individuals. Residents were also asked to answer questions that patients may pose
      about each of the procedures. The basic minimum risks, benefits, and alternatives
      to be listed and answers to the questions were validated by asking faculty
      representing general (n = 6) and vascular (n = 3) surgery to complete the
      questionnaires. RESULTS: Few residents were able to correctly list all risks,
      benefits, and alternatives of any of the procedures. Less than one-half of the
      questions that patients may ask about the procedures were correctly answered.
      CONCLUSIONS: Even though first-year residents are commonly obtaining consent for
      surgical procedures, many are unable to provide patients with the correct
      descriptions of the risks, benefits, and alternatives. Nor were they able to
      correctly answer common questions. Surgical faculty must take more time to
      educate first-year residents on the appropriate issues in informed consent for
      the procedures being performed.

PMID- 16093120
TI  - Surgical careers and preparedness of graduating residents--an outcomes-based
      study.
AB  - PURPOSE: Outcome-based measures have recently become the focus of residency
      program evaluations. The ultimate outcome of a surgical training program is the
      successful development of surgical careers by its graduates. METHODS: We
      developed a survey that was sent to all residents completing our surgical
      residency from 1989 to 1999 in order to evaluate practice location, type of
      practice, practice mixture, additional training obtained after residency, Board
      certification, and membership in the American College (ACS) or other professional
      societies. Graduates were asked to report their impression of their residency
      education program's ability to prepare them for surgical practice as well as to
      give an overall opinion of their training using a scale of 10 (high) to 1 (low).
      Solicitations were also made for means to improve the training program. RESULTS:
      Of 32 graduates sent surveys, 30 responded (94%). A total of 29 of 30 responding
      graduates (97%) are active in surgery. A total of 26 of 30 graduates are in
      private or government practice, 3 of 30 are full-time academic, and 1 of 30 is
      completing fellowship training. A total of 13 of 30 (43%) immediately entered
      practice, whereas 17 of 30 (57%) received additional fellowship training. Board
      certification has been achieved by 24 graduates. A total of 17 of 30 (59%) are
      members of the ACS, and 24 of 30 (83%) are members of at least 1 regional or
      specialty society. The average score for practice preparedness was 8.35. Overall
      score for the residency program was 8.7. Specific graduate comments demonstrated
      a perceived need for additional vascular and oncology operative experience that
      led to changes in our program. These results demonstrate an overall high
      satisfaction with our training program by graduates over the past 10 years as
      well as high success rate as evidenced by successful surgical practices by 97% of
      our graduates. CONCLUSIONS: We believe this type of outcome information provides
      valuable feedback to programs with regard to planning and development based on
      the types of careers graduates choose as well as specific changes in curriculum
      based on perceived deficiencies.

PMID- 16093121
TI  - Ampullary neoplasms: is a Whipple resection really necessary?

PMID- 16093122
TI  - Cholecystectomy for acute cholecystitis: why, when, which?

PMID- 16093124
TI  - Esophagectomy: what is the best approach?

PMID- 16093123
TI  - Cirrhotic ascites: an update.

PMID- 16093125
TI  - Management of benign gastric outlet obstruction in the adult patient.

PMID- 16093126
TI  - Rectocele.

PMID- 16093127
TI  - Update on complicated peptic ulcer disease.

PMID- 16093128
TI  - Paraesophageal hernia: current diagnosis and treatment.

PMID- 16093129
TI  - A new method of continuous venovenous rewarming.
AB  - PURPOSE: Hypothermia is a significant problem in medicine and is part of a deadly
      triad, including hypothermia, acidosis, and coagulopathy. Multiple methods of
      rewarming are used to treat moderate hypothermia. The purpose of this study was
      to compare the effectiveness of continuous venovenous rewarming (CVVR) using the
      FMS 2000 (Belmont Instrument Corp., Billerica, Massachusetts) in conjunction with
      external rewarming techniques versus external rewarming alone in the porcine
      model. METHODS: Ten subject animals, each weighing approximately 40 kg, were
      evenly divided and randomly assigned to either a control group using external
      rewarming techniques alone or the CVVR group utilizing the FMS 2000 in addition
      to the external rewarming techniques used in the control group. Hypothermia was
      induced in the swine model using cold water immersion to achieve a core
      temperature of 30 degrees C. Both esophageal and rectal temperature probes were
      used to monitor and record core body temperatures every 15 minutes during the
      experiment. Each study animal was then rewarmed until a core temperature of at
      least 37 degrees C was recorded in both the esophageal and rectal probes. The
      animals were observed clinically for 3 days after the study. RESULTS: The average
      time required to rewarm the control group was 253 minutes, compared with 113
      minutes in the CVVR group. After 30 minutes of rewarming, the difference between
      the 2 groups with respect to core temperature was statistically significant (p =
      0.002). A drop in core temperature after the initiation of rewarming, or after
      drop, was noted in the control group animals, but not in the CVVR group. This
      difference was statistically significant after 15 minutes of rewarming (p =
      0.015) CONCLUSIONS: Venovenous rewarming utilizing the FMS 2000 fluid management
      system is more effective than is standard therapy alone for rewarming in the
      moderately hypothermic porcine model. This finding may prove clinically useful in
      the treatment of patients suffering from moderate hypothermia.

PMID- 16093130
TI  - Laparoscopic repair of a large symptomatic epiphrenic esophageal diverticulum.
AB  - PURPOSE: The diagnosis of symptomatic epiphrenic esophageal diverticula is
      uncommon. Even less common are published reports regarding the efficacy of
      laparoscopic repair of this malady. METHODS: We report the case of a 59-year-old
      male patient with Parkinsonism found to have a large, symptomatic epiphrenic
      diverticulum and discuss the surgical treatment performed. The patient presented
      with a 6-month history of worsening dysphagia to both solids and liquids,
      regurgitation of undigested food, and weight loss. Barium esophagram identified
      the presence of a large distal esophageal diverticulum. Esophagoscopy confirmed
      the epiphrenic location of the diverticulum and the absence of other pathology.
      Laparoscopic transhiatal diverticulectomy was performed utilizing a
      gastrointestinal endoscopic stapler. Intraoperative esophagoscopy was performed
      to confirm resection of the diverticulum without constriction of the lumen.
      RESULTS: The patient resumed intake of liquids on postoperative day 1 after a
      water-soluble contrast esophagram revealed no extravasation. The patient was
      discharged on hospital day 3. He reported residual dysphagia to solids
      postoperatively, which appeared to resolve after pneumatic dilation. CONCLUSIONS:
      We conclude that laparoscopic epiphrenic diverticulectomy is technically feasible
      and safe. The comorbidity of Parkinsonism adds complexity to the diagnosis and
      treatment of this uncommon disorder.

PMID- 16093131
TI  - Preoperative serum TA90-IC as an adjunct to serum CA 19-9 in the diagnosis of
      pancreatic malignancy: a pilot study.
AB  - PURPOSE: Because TA90, a 90-kDa immunogenic tumor-associated antigen, is
      expressed by pancreatic cancer cells, we hypothesized that the serum level of its
      immune complex with IgG (TA90-IC) might be a useful marker for diagnosis of
      pancreatic malignancy. We also wanted to compare TA90-IC with CA 19-9 in the
      diagnosis of pancreatic cancer. METHODS: We undertook a retrospective study of
      prospectively collected sera from patients with histopathologically proven
      pancreatic malignancies. Patient sera were analyzed for TA90-IC and CA 19-9. Sera
      of sex-matched and age-matched healthy volunteers (controls) were analyzed for
      TA90-IC. The study was conducted at a tertiary medical center. Twenty-one
      patients with pancreatic malignancies and 29 controls, from whom sera had been
      obtained and cryopreserved, were included. A positive TA90-IC level was defined
      as an optical density >/= 0.410 at 405 nm following an enzyme-linked
      immunosorbent assay based on a murine monoclonal antibody. CA 19-9 levels were
      determined by immunoradiometric assay performed at outside laboratories (normal
      range, 0 to 37 U/mL). RESULTS: Of the 21 patients, 14 had positive TA90-IC levels
      and 18 had increased CA 19-9 levels (67% vs 86%; p = 0.157). The TA90-IC levels
      were significantly higher in the cancer group than in the control group (p =
      0.0003). Of the 3 patients with normal CA 19-9 levels, 2 had positive TA90-IC
      levels. The combination of both markers identified 95% of patients with
      pancreatic malignancy, a significantly higher diagnostic rate than that of either
      marker alone (p = 0.014). TA90-IC sensitivity was higher for stage II and III
      disease than for stage IV disease (82% vs 50%). CONCLUSIONS: TA90-IC assay may
      improve the prediction of pancreatic malignancy when used in combination with CA
      19-9 levels. Because TA90-IC appears to have improved diagnostic accuracy with
      smaller tumor burden, the role of TA90-IC as an adjunct to CA 19-9 in screening
      and monitoring progression of early disease warrants further investigation.

PMID- 16093132
TI  - Grand rounds. Calcified hepatic cyst.

PMID- 16093133
TI  - William Beaumont--the dedicated opportunist.

PMID- 16093134
TI  - Pheochromocytoma in quadriplegia.

PMID- 16093135
TI  - Resident resource corner. Beginning.

PMID- 16093136
TI  - Clinical profiling in surgical education.

PMID- 16093137
TI  - Performance standards improve American Board of Surgery In-Training Examination
      scores.
AB  - PURPOSE: Although several studies have evaluated factors affecting American Board
      of Surgery In-Training Examination (ABSITE) performance, none has examined the
      impact of setting a minimally acceptable standard. It was hypothesized that
      establishing such a criterion would improve ABSITE scores. METHODS: An
      expectation for residents to score at the 35th percentile or higher was
      established in 1996. The proportion of test scores above or below the 35th and
      50th percentiles for the time periods before and after institution of the
      standard were compared using Fisher's exact test. The subsequent performance of
      residents scoring below the 35th percentile was analyzed for the 2 time periods.
      RESULTS: After the institution of the standard, the proportion of scores below
      the 35th percentile decreased from 46.7% to 21.9% (p = 0.0005). Similarly, the
      proportion of scores at or above the national average increased from 42.1% to
      65.6% (p = 0.0005). After establishing the standard, fewer residents continued to
      have scores below the criterion in subsequent years. CONCLUSIONS: Establishing a
      performance criterion improved ABSITE scores. The decision to institute a
      standard must be individualized for each program. The rationale for the standard
      and a plan to assist residents failing to achieve the benchmark must be
      communicated.

PMID- 16093138
TI  - The impact of re-engineering a multi-institutional residency program on resident
      perceptions of the individual institutions.
AB  - PURPOSE: We report on the development of a survey tool used to assess resident
      perceptions of support and educational quality among multiple institutions in an
      integrated surgical residency, as well as its use in measuring the impact of re
      engineering on that program. METHODS: The University of Connecticut Integrated
      General Surgical Residency (UCIGSR) is a multisite program that was placed on
      probation by the Residency Review Committee in Surgery (RRC) in November 1998.
      This led to a re-evaluation and a re-engineering of the program. In order to
      better assess the residents' evaluation of the program, we serially examined
      their attitudes with a survey of 65 questions. A 4-point grading scale (1 = Poor,
      4 = Excellent) was used, and each resident was required to complete a survey
      beginning shortly after RRC probation was announced and at 6-month intervals.
      Seven global questions in the survey, directed at residency program support and
      educational quality, were asked for each of the 4 individual adult hospitals, for
      a total of 28 questions. Statistical analysis of the data was performed using the
      Jonckhere-Terpstra and the Mann-Whitney U tests. RESULTS: The results
      demonstrated significant improvement for all 7 questions in all 4 hospitals
      between November 1998 (S1) and November 1999 (S3). Average scores for all 7
      questions, Hospital Support (HS), Departmental Support (DS), Hospital Teaching
      (HT), Outpatient Teaching (OTC), Operating Room Teaching (ORT), Grand Rounds
      (GR), and Morbidity and Mortality Conferences (MM), improved in every hospital by
      16-28%. In S1, 1 out of 28 questions received an average score greater than or
      equal to 3, whereas on the most recent survey, 17 of 28 scored greater than or
      equal to 3 and 78.5% of the questions demonstrated statistically significant
      improvement (p < 0.05). Three of the 4 hospitals now have a combined overall
      average score greater than or equal to 3 for all 7 questions. Areas of strength
      in each hospital had the least amount of improvement yet remained highly rated.
      CONCLUSIONS: The survey was able to detect weaknesses and variation in program
      support and educational quality among institutions in our surgical program. Over
      time, a re-engineering of the process of educating surgical residents
      demonstrated a positive effect on all of the institutions. While raising the
      overall satisfaction level of the residents throughout, the greatest improvement
      occurred in the lowest rated hospitals. Despite barriers of different
      institutional cultures and geographic locations, a multi-institutional residency
      program can institute positive change uniformly, and quantitatively monitor that
      change.

PMID- 16093139
TI  - The unkindest cut of all: are international medical school graduates subjected to
      discrimination by general surgery residency programs?
AB  - PURPOSE: International medical school graduates (IMGs) have been part of the
      United States residency applicant pool for several years. There has been
      increasing discussion of an overproduction of doctors in the United States, and
      mention of limiting IMG quotas. The purpose of this study was to find out if
      measurable discrimination existed real or perceived, against IMGs. METHODS: A
      survey was performed to assess whether program directors of surgery residencies
      perceive the performance, dedication, and abilities of IMGs as being equal to
      United States medical school graduates (USMGs), and whether program directors
      believe that a preference toward USMGs exists. Surveys with 30 tailored questions
      were mailed to all members of the Association of Program Directors in Surgery.
      One hundred twenty-five surveys were returned out of 283 mailed, and 112 were
      included in the data analysis. Besides those relating to demographics, questions
      on the survey included two series of queries. One set was designed to assess
      whether the respondent reported that IMGs possessed similar skills and abilities
      as USMGs, whereas the other addressed whether respondents perceived a tendency in
      their programs to focus recruitment toward USMGs. Still others were inserted to
      confirm results of these series, and to assess whether program directors
      perceived discrimination toward IMGs in general. RESULTS: Survey results indicate
      the perception that IMGs are similar in skill and ability to USMGs, regardless of
      program size. However, a perception existed among program directors that USMGs
      were favored in the recruitment process, with more than 70% of respondents
      indicating that they believed IMGs were discriminated against. Furthermore,
      nearly 20% reported that they had been pressured to rank a less-qualified USMG
      higher than a more qualified IMG, and 22% reported that they had ranked a USMG
      higher than an IMG to avoid a reduced compliment of USMGs. CONCLUSIONS: There is
      a significant belief and perception that IMGs are indeed discriminated against,
      despite program directors seeing no clear differences in surgical skills between
      IMGs and USMGs.

PMID- 16093141
TI  - Minimally invasive mitral valve surgery: current status.

PMID- 16093140
TI  - Modernizing surgical education.

PMID- 16093142
TI  - Prophylaxis of perioperative cardiovascular morbidity and mortality.

PMID- 16093143
TI  - Transmyocardial laser revascularization (TMR) and its role in the treatment of
      patients with coronary artery disease and angina.

PMID- 16093144
TI  - DIC: treatment frontiers.

PMID- 16093145
TI  - Disastrous and deceiving.

PMID- 16093146
TI  - Endovascular grafts.

PMID- 16093147
TI  - Selected issues in deep venous thrombosis.

PMID- 16093148
TI  - Surgical thrombectomy, thrombolytics, or anticoagulation for the treatment of
      iliofemoral venous thrombosis.

PMID- 16093149
TI  - Early postoperative intestinal obstruction.

PMID- 16093150
TI  - Current diagnosis and management of gallstone pancreatitis.

PMID- 16093151
TI  - A massive intra-abdominal lipomatous neoplasm arising from the bladder.

PMID- 16093152
TI  - Sentinel lymph node evaluation is technically feasible and may improve staging in
      colorectal cancer.
AB  - PURPOSE: The accurate nodal staging of colorectal cancer (CRC) is important to
      identify those patients who may benefit from adjuvant chemotherapy. Some have
      suggested that identification of sentinel lymph nodes (SLN) may improve staging
      in CRC. We sought to determine: the feasibility of identifying SLN in CRC
      utilizing isosulfan blue dye; the accuracy of the identified SLN in predicting
      the status of the remainder of the lymph nodes in CRC; and whether a more
      thorough evaluation of SLN with serial step sectioning and immunohistochemistry
      would more accurately stage patients with CRC. METHODS: A pilot trial was
      initiated at Walter Reed Army Medical Center (WRAMC), and 17 patients with masses
      on colonoscopy and subsequent tissue diagnosis of CRC were enrolled. Patients
      underwent standard surgical resection of their CRC with wedge of mesentery
      containing draining lymph nodes. Isosulfan blue dye was injected around the tumor
      subserosally/submucosally before dividing the mesenteric portion of the resection
      (n = 7) or ex vivo (n = 10). Sentinel lymph nodes were defined as all nodes
      staining blue and were dissected from the mesentery in the operating room. The
      SLN were sent separately for standard bivalving and hematoxylin and eosin
      staining (H&E) followed by serial step sectioning and immunohistochemistry (IHC)
      staining for cytokeratin. RESULTS: Seventeen patients (6 men, 11 women) were
      enrolled. The average preoperative carcinoembryonic antigen (CEA) was 5.9 (range,
      1.2 to 18.9), and the average postoperative CEA was 2.8 (range, 0.7 to 9.1). One
      patient had a T1 tumor, 6 patients had T2 tumors, and 10 patients had T3 tumors
      on final pathology. Five cancers were well differentiated, 11 were moderately
      differentiated, and 1 was poorly differentiated. In all 17 cases, SLN were
      identified. A mean of 5.5 SLN was found per specimen (range, 2 to 11) with no
      difference noted between injection techniques (in vivo vs ex vivo). An additional
      12 nonsentinel lymph nodes (range, 1 to 29) were identified per specimen. Ten
      patients had negative SLN and non-SLN. Seven patients were found to have positive
      SLN (3 by H&E, 2 by serial step sectioning, and 2 by IHC only). CONCLUSIONS: The
      isosulfan blue technique is technically feasible to allow identification of
      sentinel lymph nodes. In this study, no false-negative SLN occurred. A total of 7
      patients had positive SLN; more importantly, 4 patients were upstaged as a result
      of serial step sectioning and immunohistochemistry staining. We hypothesize that
      this method may help pathologists find appropriate lymph nodes for more detailed
      analysis. As a result, patients may be more accurately staged and counseled for
      adjuvant chemotherapy, which has been shown to improve survival in node-positive
      CRC. Further studies should be undertaken to test these preliminary findings.

PMID- 16093153
TI  - Surgical caseload in army general surgery programs: a 10-year retrospective.
AB  - PURPOSE: Over the past decade, the Army Medical Department (AMEDD) has been
      affected by a military-wide drawdown. The volume and acuity of patients appears
      to be declining, raising questions regarding quantity and quality in Army
      surgical training programs. The purpose of this study is to examine the caseloads
      of Army general surgery programs compared with national averages, and to compare
      the board examination performance of Army residents with national pass rates.
      METHODS: The program directors of all 6 Army training programs were requested to
      submit resident caseloads and performance on qualifying and certifying
      examinations from 1990 to 2000. The Accreditation Council for Graduate Medical
      Education (ACGME) and the American Board of Surgery (ABS) provided resident
      statistics summaries and board examination statistics, respectively, for the same
      period. Total caseloads, chief resident cases, performance in defined categories,
      and board pass rates of military residents were compared with national averages.
      RESULTS: Four of the 6 programs submitted the requested data. The average
      caseload for Army residents, both total and chief residents, has been lower than
      the national average over the past decade. Nationally, total case numbers have
      gradually increased while military changes have been variable. The number of
      chief resident cases has trended steadily downward in Army programs at a rate
      exceeding the national average. The volume of procedures in endoscopy, thoracic,
      and breast surgery in the Army generally exceeds those recorded outside of the
      military. Despite the decline in surgical cases in the military, the pass rates
      in both the certifying and qualifying examinations among Army graduates have been
      consistently higher than the national average. CONCLUSIONS: Residents who train
      in Army programs perform fewer operative cases than do their counterparts in
      civilian programs. The downward trend in the number of chief resident cases over
      the last 10 years is likely reflective of the changes in military medicine.
      Despite these trends, Army residency graduates continue to exceed national
      performance averages on the ABS qualifying and certifying examinations.

PMID- 16093154
TI  - The effect of changing gamma count threshold on sentinel lymph node accuracy.
AB  - PURPOSE: Sentinel lymph node (SLN) biopsy has been increasingly accepted in many
      centers as an alternative to axillary lymph node dissection in the nodal staging
      of breast cancer. The goal of SLN biopsy is to accurately stage the axilla while
      minimizing postoperative morbidity. Theoretically, the continuing search for SLNs
      disrupts additional lymphatics and impacts on operative time. The gamma count
      threshold is a predefined threshold percentage of the ex vivo count of the
      "hottest" SLN, which when applied to each individually excised lymph node
      determines whether a given lymph node is the SLN or a non-SLN. The higher the
      threshold percentage, the less the number of lymph nodes will meet the criteria
      of being an SLN. This study examines the hypothesis that changing the gamma count
      threshold from 10% to 50% will not significantly affect accuracy or the false
      negative rate. METHODS: We retrospectively reviewed the charts of patients who
      underwent SLN biopsy with or without completion axillary lymph node dissection
      from March 1995 to January 2001 at Walter Reed Army Medical Center. Data were
      collected on gamma counts for each SLN and histopathology of each SLN. For each
      SLN ex vivo gamma count, percentage of the ex vivo gamma count of the "hottest"
      SLN was calculated. RESULTS: The SLN identification success rate was 94% (163 out
      of 174 patients). On average, 2.07 SLNs were removed per patient and 58% of
      patients had more than 1 SLN removed (94 out of 163 patients). Only 10% had 4 or
      more SLNs removed (17 out of 163 patients). Sentinel lymph node metastasis was
      found in 21% of patients (35 of 163 patients). Of these 35 patients with positive
      SLNs, 8 patients had a negative "hottest" SLN when a less radioactive SLN was
      positive for metastasis. Changing the gamma count threshold from 10% to 50%
      lowers the extrapolated accuracy from 98% to 95% and increases the extrapolated
      false-negative rate from 8% to 21%. CONCLUSIONS: The accuracy and false-negative
      rate of SLN biopsy varies based on the lower limit gamma threshold. Maintaining
      our 10% gamma count threshold results in acceptable accuracy and false-negative
      rates comparable to reported literature.

PMID- 16093155
TI  - Grand rounds. Chest pain in a woman with Marfan syndrome.

PMID- 16093156
TI  - Are we meeting the needs of our surgical graduates: a survey study.

PMID- 16093157
TI  - Commentary.

PMID- 16093158
TI  - Benefits of surgical experience in a third-world country during residency.
AB  - PURPOSE: Completion of a United States surgical residency enables the graduate to
      provide service in most populated areas. Graduates are technically well trained
      and efficient in performing most surgeries. United States-based teaching
      facilities are generally furnished with technically advanced supplies and
      equipment. Access to financial reserve is also available. Surgery in third-world
      countries, however, can be challenging. These countries, particularly in the
      outskirts, lack supplies and innovation, such as advanced equipment, medication,
      and personnel. Compounding the problem, patients tend to have advanced pathology
      and diminished financial means. METHODS: The United States-based surgical team
      annually collaborated with a medical mission to provide service to a rural
      community of the Dominican Republic. A senior-level surgery resident accompanied
      the surgeon. Surgical supplies were donated and brought with the team. The
      average number of cases performed was approximately 37 per week. All procedures
      were performed for symptomatic pathology. All patients were preoperatively
      screened and evaluated for comorbidities. RESULTS: No immediate complications
      occurred. Local physicians provide long-term follow-up. Pediatric procedures were
      not performed secondary to lack of postoperative resources. CONCLUSIONS: Surgical
      experience is beneficial to the recipient community and the resident surgeon. The
      extent of pathology and lack of resources enforces efficiency and broadens
      skills. This opportunity can potentially prepare surgeons for the growing need of
      rural surgery.

PMID- 16093159
TI  - Laparoscopic orchiectomy for unilateral intra-abdominal testis.
AB  - PURPOSE: A brief description of laparoscopic orchiectomy for undescended testis
      and a representative case report. METHODS: A 22-year-old Chinese man was admitted
      for removal of an intra-abdominal testis. Laparoscopic orchiectomy was used to
      remove the testis at the time of laparoscopic orchiectomy. The patient had an
      uneventful postoperative course. RESULTS: A concurrent inguinal hernia was
      discovered during the procedure and repaired. CONCLUSIONS: The use of
      laparoscopic surgery has proven to be a safe and effective means of treatment for
      the intra-abdominal testis.

PMID- 16093160
TI  - Polypoid esophageal adenocarcinoma--a clinicopathological variant of esophageal
      cancer?
AB  - PURPOSE: Neoplastic polyps are common in the colon, but not elsewhere in the
      gastrointestinal tract. They are rare at the gastroesophageal junction,
      especially associated with Barrett's dysplasia or adenocarcinoma. We identify a
      subset of early esophageal adenocarcinomas that present as symptomatic polyps
      with gastrointestinal bleeding, reflux, and even dysphagia. Because little is
      known about polypoid esophageal adenocarcinomas, we examine the clinical
      presentation, pathological features, and postoperative outcomes of these lesions.
      METHODS: We defined esophageal polyps as macroscopic, well-demarcated projections
      above the mucosa that project the greater percentage of their mass into the lumen
      without central ulceration. From a consecutive series of 400 patients who
      underwent esophagectomies for adenocarcinoma (1988 to 2000), 14 (4%) had polyps
      on presentation. Clinical records, pathology reports, photographs, and original
      slides of these resected specimens were reviewed. RESULTS: All patients with
      polyps had early staged esophageal adenocarcinomas. Lymph node involvement was
      found in only 4 patients, and no patients with distant metastases were found. All
      but 1 patient (13 of 14; 93%) were symptomatic at diagnosis. Most presented
      either with gastrointestinal bleeding or gastroesophageal reflux (11 of 14; 79%).
      Only 2 patients complained of mild dysphagia, and mean weight loss of the series
      was minimal at 1.3 +/- 4.0 kg (range, 0 to 15 kg). Barrett's was present in 10
      patients (71%), and in 80% of these cases, high-grade dysplasia was found. The
      polyps were small 3.4 +/- 1.1 cm, and most contained poorly differentiated
      adenocarcinomas. No postoperative mortalities occurred, and follow-up was
      complete at 100%. Actuarial 2-year survival was 88%, with a mean survival of 61.3
      months. Recurrent disease was identified in 4 patients. CONCLUSIONS: Polypoid
      adenocarcinomas of the distal esophagus are a subset of esophageal cancer that
      produce clear symptoms at an early tumor stage, which allows prompt detection and
      favorable prognosis. Their pathological features and demographics suggest an
      origin via the Barrett's esophagus-dysplasia-carcinoma sequence.

PMID- 16093161
TI  - Forest Dewey Dodrill, MD: pioneer cardiovascular surgeon.

PMID- 16093162
TI  - Residency, fellowships, and pseudo fellowships: whither general surgery?

PMID- 16093163
TI  - The ACGME competencies.

PMID- 16093164
TI  - Coagulopathy review.

PMID- 16093165
TI  - Percutaneous endoscopic gastrostomies, tubes, and the end of the line?

PMID- 16093166
TI  - The effects of volume on surgical practice.

PMID- 16093167
TI  - Laparoscopic pyloromyotomy update.

PMID- 16093168
TI  - Pediatric thoracoscopic surgery.

PMID- 16093169
TI  - Protective ventilatory strategies in adult and pediatric respiratory distress
      syndrome.

PMID- 16093170
TI  - Pyloric stenosis update.

PMID- 16093171
TI  - Blood substitutes: an update.

PMID- 16093172
TI  - Cervical trauma: injury identification and timing of surgical stabilization.

PMID- 16093173
TI  - Percutaneous tracheostomy.

PMID- 16093174
TI  - So you've had a minor head injury...now what?

PMID- 16093175
TI  - The PDA saga continues: updates and essential and nonessential gadgets.

PMID- 16093176
TI  - The evolving management of gastric outlet obstruction from peptic ulcer disease.

PMID- 16093177
TI  - Appendiceal torsion in an adult: case report and review of the literature.
AB  - PURPOSE: Torsion of the appendix is a rare cause of acute abdomen with
      presentation, treatment, and prognosis virtually identical to that of acute
      appendicitis. METHODS: We present a case of appendiceal torsion in a 44-year-old
      male, which is to our knowledge the first in an African-American man, and we
      review all of the reported adult cases in the English language literature.
      CONCLUSION: This condition may have occurred when a normal appendix is
      encountered and no other pathologic findings exist.

PMID- 16093178
TI  - Audition electives during surgical residency and selection for post-residency
      fellowship positions.
AB  - PURPOSE: This study sought to determine the impact of surgical resident elective
      rotations, termed "audition" electives, upon the selection processes of surgical
      subspecialty residency positions, and to establish the incidence and character of
      resident personal contact before selection with the program where they ultimately
      located in order to appropriately council residents in achieving their
      educational and professional goals. METHODS: A national survey of all surgical
      subspecialty programs for academic year 1999/2000 was conducted to determine
      whether the current first-year subspecialty residents had been on a clinical
      rotation of the subspecialty at their institution during their general surgery
      residency, had participated in research efforts of the specific subspecialty at
      their institution, and whether the resident's prerequisite general surgery
      training was obtained at their parent sponsoring institution. RESULTS: Seventy
      two percent of 348 programs responded, representing 396 beginning surgical
      subspecialty residents for the surveyed academic year. Overall, 73% of first-year
      surgical subspecialty residents did not have direct prior personal contact with
      their subspecialty program either through a clinical rotation at the institution
      or through research as a general surgery resident. Eighty-four percent of first
      year surgical subspecialty residents did not complete their general surgery
      residency at the parent sponsoring institution of the subspecialty program.
      CONCLUSIONS: An audition elective does not appear to significantly influence the
      process of surgical subspecialty resident selection. The findings further
      validate the fairness of the selection processes.

PMID- 16093179
TI  - Coexistence of Mirizzi Type II syndrome with a parapapillary choledochoduodenal
      fistula: a case report.

PMID- 16093180
TI  - Flail chest caused by penetrating trauma: a case report.

PMID- 16093181
TI  - Prevalence of teaching sentinel lymph node biopsy for breast cancer in general
      surgery residency programs.
AB  - PURPOSE: Sentinel lymphadenectomy (SLNB) for the evaluation of clinically
      negative lymph nodes in women with invasive breast cancer is rapidly gaining
      acceptance within the surgical community. The purpose of this study was to
      document the prevalence of teaching SLNB to residents in general surgery training
      programs in the United States. METHODS: The Fellowship and Residency Electronic
      Interactive Database (FREIDA) was searched for a listing of all general surgery
      residency programs. A short questionnaire was mailed to the program director of
      each residency program listed. The program directors were asked whether general
      surgery residents are taught the technique of performing SLNB for breast cancer,
      and how the procedure is performed at their institutions. RESULTS: Of the 255
      surgical programs listed in FREIDA, 191 or 75% responded to the survey. Of
      responding programs, 92% are currently teaching surgical residents SLNB, whereas
      4% plan on adding SLNB to the curriculum within the next academic year. A total
      of 74% of programs are performing SLNB as part of an organized hospital protocol,
      whereas 40% routinely follow SLNB with an axillary node dissection. A total of
      89% of the programs use both sulfur colloid radioisotope and isosulfan blue dye,
      whereas 7% use dye alone, and 4% use only radioisotope. CONCLUSIONS: The practice
      of performing SLNB for the purpose of detecting occult nodal metastases in breast
      cancer is being taught at most surgery training programs in this country. In the
      less than 6 years since the modification of this technique for the treatment of
      breast disease, it has become the standard of care for treating women with
      invasive breast cancer with clinically negative axillary lymph nodes at training
      hospitals in the United States.

PMID- 16093182
TI  - A resident's guide to personal finance.

PMID- 16093183
TI  - Roscoe Reid Graham (1890 to 1948): the man of the patch.

PMID- 16093184
TI  - Airbag-related eye trauma: a review of current literature.

PMID- 16093185
TI  - Parotid neoplasm: the lump near the mandible?

PMID- 16093187
TI  - Thyroiditis: is there a place for surgical management?

PMID- 16093186
TI  - Regional anesthesia and thyroidectomy: local anesthesia for thyroidectomies?

PMID- 16093188
TI  - Neurotrauma: lingering issues.

PMID- 16093189
TI  - Review of technological advances in neurosurgery.

PMID- 16093191
TI  - Postoperative pneumonia.

PMID- 16093190
TI  - Update on the lumbar disk syndrome.

PMID- 16093192
TI  - Achalasia: a brief review of treatment options and efficacy.

PMID- 16093193
TI  - The minimally invasive surgical approach to achalasia: a new standard of care?

PMID- 16093194
TI  - Radiofrequency coagulation with Thiersch's operation--a better palliative
      treatment in prolapse rectum.
AB  - PURPOSE: Thiersch operation is an age-old popular option for treatment of
      complete rectal prolapse (proctodentia) in elderly patients. This procedure is
      simple, easy to perform, and with very rare postoperative complications of any
      severe nature. This is especially suitable for those patients who are unfit for
      extensive abdominal surgical procedures in practice today. This procedure does
      help in mechanically supporting and containing the prolapse. Although the
      procedure is not curative, the confining of the prolapse in the anal canal does
      ensure a relief from symptoms generated by the prolapse. Nevertheless, withdrawal
      of the occlusive material used is inevitably followed by recurrence of the
      prolapse, making the procedure a failure in achieving a prolonged relief.
      METHODS: Looking at this drawback, we have made an addition to this conventional
      procedure by introducing circumferential coagulation of the subanodermal region
      through a radio frequency device. This results in inducing fibrosis and forming a
      zone of band. The added maneuver constricts the anal opening permanently and thus
      aids in reinforcement of the atonic sphincter. The study was carried out in 8
      patients. Their average age was 57 years. All of them had complete prolapse of
      the rectum with associated features. Two of them were in early fifties, but they
      refused to undergo extensive procedures and opted for this method considered
      cheaper and quicker. RESULTS: A follow-up for a period ranging from 15 to 18
      months was found satisfactory. None of the patients had any prolapse or its
      sequel. Not a single case was reported for any sinus or discharge from the site
      of incision. The incision site was well consolidated, and the knot or the thread
      could not be felt when seen after 12 months. CONCLUSIONS: The study shows that
      radio frequency coagulation followed by Theirsch operation for complete rectal
      prolapse in the elderly has been found to be relatively easy to perform. Except
      for the radio surgical unit, no special instrumentation is needed. The results of
      this procedure have been found to be gratifying in all the patients. It is felt
      that on appropriate selection of the patients and employing this new technique of
      operation would prove a boon in treatment of this problem. A further work in this
      direction and longer follow-up of the treated patients are bound to bring about
      exciting new dimensions in the field.

PMID- 16093195
TI  - Successful treatment of malignant rhabdoid tumor of the vulva in an older
      patient: a case report and review of the literature.
AB  - PURPOSE: Malignant rhabdoid tumor (MRT) of the vulva is a rare and very
      aggressive neoplasm. Only 7 cases have been reported thus far in the English
      literature. This case reports the oldest patient to date with MRT. This 63 year
      old was successfully treated with surgery and radiation therapy. The current
      literature is reviewed, and different treatment modalities are considered and
      evaluated.

PMID- 16093196
TI  - Resident resource corner. Association of Women Surgeons.

PMID- 16093197
TI  - Practical digital photography for surgeons.

PMID- 16093198
TI  - Competitive displacement of clozapine from plasma proteins in normolipidemic and
      hyperlipidemic plasma samples: clinical implications.
AB  - OBJECTIVE: This study assesses whether competitive displacement of clozapine by
      warfarin affects clozapine's overall plasma distribution. METHODS: Warfarin
      sodium was preincubated in normolipidemic and hyperlipidemic plasma samples in
      varying concentrations. Following the preincubation with warfarin, [3H]clozapine
      mixed with unlabeled clozapine was added to the plasma samples. The plasma was
      separated into its lipoprotein and lipoprotein-deficient fractions by density
      gradient ultracentrifugation, and clozapine distribution was determined. RESULTS:
      When normolipidemic plasma was preincubated with various concentrations of
      warfarin, no significant redistribution of clozapine was noted among the various
      plasma lipoprotein fractions. However, in the case of the hyperlipidemic plasma,
      preincubating with warfarin did result in a significant redistribution of
      clozapine from the lipoprotein-deficient fraction to the very-low-density and low
      density fractions of lipoproteins. Based on pharmacokinetic principles, the
      steady-state unbound concentration of clozapine in normolipidemic and
      hyperlipidemic plasma is not expected to change. CONCLUSION: Although no change
      in the steady-state unbound (active) concentration of clozapine would predict no
      change in clinical status, it is possible that this may only apply to the
      individuals with a normal lipid profile. We believe clozapine's association with
      lipoproteins (particularly triglycerides) may actually increase clozapine's
      effectiveness.

PMID- 16093199
TI  - Eudragit NE40-drug mixed coating system for controlling drug release of core
      pellets.
AB  - This study was aimed at developing a controlled-release coating system around
      core pellets with aqueous dispersion, along with some water channeling agents.
      Core pellets of diltiazem were prepared using the extrusion-spheronization
      technique and subsequently coated with aqueous dispersion of Eudragit NE40 alone,
      or drug-polymer mixtures using bottom-spray fluidized bed coater. The lag time in
      drug release profiles increased as the coating levels of Eudragit NE40 were
      increased, whereas no lag time was observed in core pellets coated with drug
      polymer mixtures. Mixed coating at the 7% level exhibited comparatively better
      release profiles and provided desirable release rates during the 12-hour testing
      interval. Diltiazem HCl release from mixed coating was fairly independent of pH
      and drug loading. Curing of coated pellets was found to be an essential step for
      stable drug release profiles. The selection of core size range had remarkable
      effect on drug release rate and was considerably reduced by using greater core
      size.

PMID- 16093200
TI  - Self-microemulsifying drug delivery systems (SMEDDS) for improving in vitro
      dissolution and oral absorption of Pueraria lobata isoflavone.
AB  - The aim of our investigation was to develop and characterize self
      microemulsifying drug delivery systems (SMEDDS) of Pueraria lobata isoflavone to
      improve its in vitro dissolution and oral absorption in beagle dogs. SMEDDS
      consisted of oil (ethyl oleate), a surfactant (Tween 80), and a cosurfactant
      (Transcutol P). In all the SMEDDS, the level of Pueraria lobata isoflavone was
      fixed at 20% w/w of the vehicle. The in vitro self-microemulsification properties
      and droplet size analysis of SMEDDS were studied following their addition to
      water under mild agitation. A pseudoternary phase diagram was constructed
      identifying the efficient self-microemulsification region. From these
      investigations, an optimized formulation was selected and its dissolution and
      bioavailability were compared with a tablet formulation in beagle dogs. The in
      vitro dissolution rate of puerarin from SMEDDS was more than threefold faster
      than that from Yufengningxin tablets (Pueraria lobata isoflavone tablets). A 2.5
      fold increase in the relative bioavailability was observed for the SMEDDS
      compared with Yufengningxin tablets. The absolute bioavailability of the SMEDDS
      was 82.32 +/- 15.51%, which was significantly improved compared with that of
      Yufengningxin tablets. These results demonstrate the potential of SMEDDS as an
      efficient way of improving the oral absorption of Pueraria lobata isoflavone.

PMID- 16093201
TI  - Three generations of cyclosporine a formulations: an in vitro comparison.
AB  - When the microemulsion formulation of the critical dose drug cyclosporine A (CsA)
      (Sandimmun Optoral) was introduced in the mid-1990s, it became clear that this
      new formulation improves the oral bioavailability of CsA and has a positive
      influence on its pharmacokinetic variability. Previous studies with the original
      CsA formulation (Sandimmun) showed that the size of the emulsion droplets and
      concomitant food intake has an effect on the absorption of CsA from the small
      intestine when orally administered. It was suggested that these effects might
      have an influence on the drugs' pharmacokinetic parameters. In this study, we
      focused on the two above-mentioned aspects and compared the first and second
      generations of CsA products (Sandimmun, Sandimmun Optoral) to generic CsA
      formulations by analyzing the contents of cyclosporine A gel capsules with
      respect to their emulsion droplet and micelle sizes using photon correlation
      spectroscopy (PCS). We tried to discern any differences in droplet size between
      different generations of CsA formulations, primarily the second and third
      generation, through simple physical tests. Because a high fat content food may
      influence the absorption of CsA, we also determined the distribution of CsA
      between hydrophilic and lipophilic phases using high-performance liquid
      chromatography analysis. It became clear that when compared under simple physical
      conditions, established cyclosporine formulations and new generic products show
      significant differences in droplet size and distribution between an aqueous phase
      and a high fat content food. Whether these differences are of clinical relevance
      remains to be investigated.

PMID- 16093202
TI  - Oral sustained delivery of atenolol from floating matrix tablets-formulation and
      in vitro evaluation.
AB  - Floating matrix tablets of atenolol were developed to prolong gastric residence
      time and increase drug bioavailability. Atenolol was chosen as a model drug
      because it is poorly absorbed from the lower gastrointestinal tract. The tablets
      were prepared by direct compression technique, using polymers such as
      hydroxypropyl methylcellulose (HPMC K15M, K4M), guargum (GG), and sodium
      carboxymethylcellulose (SCMC), alone or in combination, and other standard
      excipients. Tablets were evaluated for physical characteristics viz. hardness,
      swelling index, floating capacity, thickness, and weight variation. Further,
      tablets were evaluated for in vitro release characteristics for 8 hr. The effect
      of effervescent on buoyancy and drug release pattern was also studied. In vitro
      release mechanism was evaluated by linear regression analysis. GG- and SCMC-based
      matrix tablets showed significantly greater swelling indices compared with other
      batches. The tablets exhibited controlled and prolonged drug release profiles
      while floating over the dissolution medium.

PMID- 16093203
TI  - Preparation, in vitro and in vivo evaluation of liposomal/niosomal gel delivery
      systems for clotrimazole.
AB  - Clotrimazole, which is an imidazole derivative antifungal agent, was widely used
      for the treatment of mycotic infections of the genitourinary tract. To develop
      alternative formulation for the vaginal administration of clotrimazole to provide
      sustained and controlled release of appropriate drug for local vaginal therapy,
      liposomes/niosomes were evaluated as delivery vehicles. To optimize the
      preparation of liposomes/niosomes with regard to size and entrapment efficiency,
      multilamellar liposomes/niosomes containing drug were prepared by lipid hydration
      method. The prepared liposomes/niosomes were incorporated into 2% carbopol gel,
      and the systems were evaluated for drug stability in phosphate-buffered saline
      (pH 7.4) and simulated vaginal fluid at 37 +/- 1 degrees C. Further, the vesicle
      gel system was evaluated by antifungal activity and tolerability on tissue level
      in rat.

PMID- 16093204
TI  - Chitosan and sodium sulfate as excipients in the preparation of prolonged release
      theophylline tablets.
AB  - The major objectives of this study were to monitor the effect of cross-linking of
      cationic chitosan in acidic media with sulfate anion during granules preparation
      by wet granulation method prior to tableting using theophylline (TPH) as a model
      drug. The prepared granules and the compressed tablets were subjected to in vitro
      evaluation. The properties of the prepared matrix granules and the compressed
      tablets were dependent on chitosan:sodium sulfate weight ratios, chitosan
      content, and molecular weight of chitosan. The prepared granules of all batches
      showed excellent to passable flowability and were suitable for compression into
      tablets. Most of the granules were hard and expected to withstand handling during
      the subsequent compression into tablets. Granules with high friabilities were
      only those prepared with a high amount of sodium sulfate or low amount of
      chitosan. Compression of granule batches yield nondisintegrating tablets that
      showed a decrease in tensile strength with the increase of sodium sulfate content
      at high chitosan:sodium sulfate weight ratio or with decrease of chitosan
      content. On the other hand, friability of tablets was increased in the presence
      of an excessive amount of sodium sulfate and low chitosan content as observed
      with granules. Slow TPH release from the formulated tablets was achieved at 1:0.5
      and 1:1 chitosan:sodium sulfate weight ratios where all or most of the cationic
      chitosan and sulfate anions were used in a cross-linking reaction during wet
      granulation. Ratios of 1:2 and 1:3 showed fast drug release, which support the
      hypothesis that excessive unreacted water-soluble sodium sulfate might increase
      the porosity of the nondesintegrating tablets during dissolution. Slow drug
      release was also obtained with high molecular weight chitosan, whereas changing
      the hardness of the tablets did not significantly change the release profile of
      the drug as long as the tablets are intact during dissolution. Furthermore, slow
      drug release was observed as the total amount of chitosan was increased in the
      formulated tablets. A comparative in vivo study between the chosen formulated
      tablets (1:1 chitosan:sodium sulfate ratio that contains 10% high molecular
      weight chitosan) and the commercial Quibron tablets indicated prolonged
      appearance of the drug in dogs' plasma for both formulations with no significant
      differences (p > 0.05) in rate and extent of drug absorption. The formulated
      tablets showed 103.16% bioavailability relative to that of the commercial
      tablets.

PMID- 16093205
TI  - Characterization of the absorption of theophylline from immediate- and controlled
      release dosage forms with a numerical approach using the in vitro dissolution
      permeation process using caco-2 cells.
AB  - After oral administration, drug absorption rate is recognized to be dependent on
      two major factors: dissolution and intestinal cells permeability. Caco-2
      monolayer cells have been largely used as a permeation study model. In this
      study, a numerical approach funded on an exponential first-order time
      relationship was tested to compare immediate- and controlled-release tablets of
      theophylline using a dissolution-permeation system. The dissolution performance
      using USP II paddle apparatus was coupled to the permeability studies
      investigated in Caco-2 cell monolayers. The dissolved samples were taken at
      different times; their pH and osmolarity were adjusted to render them suitable to
      Caco-2 permeability studies (osmolarity = 300 mosm, pH = 7.4). The experimental
      data show that the dissolution fits the exponential first-order relationship
      rate. The permeability values were in a range of 4.45 10(- 6)-5.28 10(- 6) cm/s,
      and percentages of absorbed drug dose were dependent on the fraction initially
      present in the donor compartment, indicating that absorption of theophylline was
      dissolution rate limited. Plotting experimental absorbed fractions (F(a)) against
      experimental dissolved fractions (F(d)) show that permeation is the rate-limiting
      step in drug absorption process in the extended release form of theophylline. Our
      results demonstrate a general agreement between observed F(a)/F(d) relationships
      and theoretical F(a)/F(d) relationships obtained with our approach funded on
      dissolution and permeation behavior. We concluded that the couple dissolution
      caco-2 system could be a useful tool to characterize intestinal permeation for a
      new formulation of a drug compared with the conventional one.

PMID- 16093206
TI  - Enhanced in vitro percutaneous absorption and in vivo anti-inflammatory effect of
      a selective cyclooxygenase inhibitor using microemulsion.
AB  - Celecoxib, a specific COX-2 inhibitor, was recently approved for the treatment of
      rheumatoid and osteoarthritis, acute pain, familial adenomatous polyposis and
      primary dysmenorrhea. Oral administration of celecoxib is effective against
      ultraviolet B radiation (UVB)-induced skin carcinogenesis; however, its clinical
      use is restricted because of its failure to block the characteristic cutaneous
      inflammatory response and lower availability at the site of inflammation. Topical
      application of celecoxib has been effective compared with oral in certain
      clinical conditions. The present study was undertaken to develop and investigate
      the development of microemulsion system (isopropyl myristate/medium-chain
      glyceride/polysorbate 80/water) for topical delivery of celecoxib. The
      pseudoternary phase diagram was constructed with constant surfactant
      concentration, and several compositions were identified and characterized by
      using dynamic light scattering. The in vitro permeation rate of celecoxib through
      rat skin was determined for microemulsions, microemulsion gel, and cream by using
      the modified Franz-type diffusion cell. In all formulations tested, celecoxib
      permeated more quickly, and the microemulsions increased the permeation rate of
      celecoxib up to 5 and 11 times compared with those of microemulsion gel and
      cream, respectively. Increasing the concentration of medium-chain mono-/di
      glyceride in microemulsion imparted increased droplet size and viscosity and
      decreased diffusion coefficient. In vivo anti-inflammatory study suggested that
      the developed microemulsion formulations might serve as potential drug vehicle
      for the prevention of UVB-induced skin cancer.

PMID- 16093207
TI  - Dissolution, solubility, XRD, and DSC studies on flurbiprofen-nicotinamide solid
      dispersions.
AB  - Flurbiprofen-nicotinamide solid dispersions were prepared by the fusion method.
      The solid dispersions were evaluated for dissolution rate. The drug-carrier
      interaction in the liquid and solid states were studied by using phase solubility
      analysis, phase diagram, X-ray diffraction (XRD), and differential scanning
      calorimentry (DSC). Solid dispersions gave fast and rapid dissolution of
      flurbiprofen compared with the pure drug and the physical mixture. Phase diagram
      and DSC indicated that flurbiprofen and nicotinamide form a eutectic mixture. The
      aqueous solubility of flurbiprofen was enhanced in the presence of nicotinamide.

PMID- 16093208
TI  - Characterization and dissolution properties of ketoprofen in binary and ternary
      solid dispersions with polyethylene glycol and surfactants.
AB  - The effect of incorporation of an anionic [sodium dodecyl sulfate (SDS) or
      dioctylsulfosuccinate (DSS)] or nonionic [Tween 60 (TW60)] surfactant on the
      properties of ketoprofen solid dispersions in polyethylene glycol 15000 (PEG) has
      been investigated. Physicochemical and morphological properties of the various
      solid systems were determined by differential scanning calorimetry, hot stage
      microscopy, X-ray powder diffraction analysis, and scanning electron microscopy.
      The results from dissolution studies, performed according to the USP 24 basket
      method, indicated that all ternary dispersed systems were significantly (p <
      0.001) more efficacious than the corresponding binary ones, by virtue of the
      additive wetting and solubilizing effect due to the presence of the surfactant.
      The relative effectiveness of the incorporated surfactant was in the same order
      as found in phase-solubility studies (i.e., SDS > DSS > TW60). With regard to the
      solid dispersion preparation method, coevaporated products always gave better
      results than the corresponding cofused ones; however, this effect was
      statistically significant (p < 0.001) only in the initial phase of the
      dissolution process. The most effective solid dispersion was the 10-80-10 w/w
      drug-PEG-SDS ternary coevaporate, which allowed dissolution of 50% drug after
      only 6 min (in comparison with > 120 min for drug alone and 17 min for the binary
      coevaporate) and dissolution of about 100% drug after 30 min (in comparison with
      > 120 min for the binary coevaporate).

PMID- 16093209
TI  - Alginate-coated alginate-polyethyleneimine beads for prolonged release of
      furosemide in simulated intestinal fluid.
AB  - Furosemide-loaded calcium alginate (ALG), calcium alginate-polyethyleneimine (ALG
      PEI) and alginate-coated ALG-PEI (ALG-PEI-ALG) beads were prepared by
      ionotropic/polyelectrolyte complexation method to achieve controlled release of
      the drug. Effects of several formulation factors on the characteristics of the
      beads were investigated. Although variation in formulation factors did not
      influence the drug-loading efficiency (DLE) of ALG beads, rapid release of the
      drug in simulated intestinal fluid (SIF) could not be prevented. PEI treatment of
      ALG beads, however, prolonged the drug release considerably. Ionic interaction,
      as appeared from FTIR studies, between alginate and PEI led to the formation of
      polyelectrolyte complex membrane, the thickness of which was dependent on the
      conditions of PEI treatment as demonstrated by scanning electron microscopy
      (SEM). The membrane acted as a physical barrier to drug release from ALG-PEI
      beads. Alginate coating of ALG-PEI beads further prolonged the release of the
      drug by increasing membrane thickness and reducing swelling of the beads possibly
      by blocking the surface pores. Differential scanning calorimetry (DSC) study
      indicated that drug was not degraded by PEI treatment. The release data from ALG
      PEI beads showed a good fit in power law expression, whereas the release data
      from ALG-PEI-ALG beads were found to fit in modified power law expression, and
      the mechanism of drug release changed from super case II transport to nearly
      Fickian transport, depending on the degree of gelation and formation of
      polyelectrolyte complex membrane.

PMID- 16093210
TI  - In vivo skin permeation of sodium naproxen formulated in pluronic F-127 gels:
      effect of Azone and Transcutol.
AB  - The objective of this study was to determine the penetration of sodium naproxen,
      formulated in Pluronic F-127 (PF-127) gels containing Azone and Transcutol as
      penetration enhancers, through human skin in vivo. It was found that the
      combination of Azone and Transcutol in PF-127 gels enhanced sodium naproxen
      penetration, with enhancement ratios of up to two fold compared with the
      formulation containing only Transcutol. These results were confirmed by TEWL and
      ATR-FTIR spectroscopy, suggesting a synergic action for Azone and Transcutol.
      Because of the thermo-reversible behavior of Pluronic gels, the influence of the
      components added to the gel formulations on viscosity, as a function of
      temperature, was also studied.

PMID- 16093211
TI  - Release of ciprofloxacin from chondroitin 6-sulfate-graft-poloxamer hydrogel in
      vitro for ophthalmic drug delivery.
AB  - The system was designed to use Poloxamer as a vehicle for ophthalmic drug
      delivery using in situ gel formation property. To enhance the wound healing and
      cell adhesion as well as transparency of Poloxamer hydrogel, chondroitin 6
      sulfate (C6S) was introduced into Poloxamer. For this purpose, mono amine
      terminated Poloxamer (MATP), which was end-capped with ethylene amine group only
      in one side of terminal hydroxyl groups of Poloxamer, was synthesized.
      Subsequently, C6S-graft-Poloxamer copolymer (C6S-g-Poloxamer) was prepared by
      reaction between the amine groups of MATP and carboxyl groups of C6S in the
      presence of 1-ethyl-3-(3-dimethylaminopropyl)-carboimide (EDC). The coupling of
      MATP with C6S was clarified by 1H-NMR and FT-IR spectroscopy. The gelation
      temperature of graft copolymers was determined by measuring the temperature at
      which immobility of the meniscus in each solution was first noted. Release
      behavior of ciprofloxacin from C6S-g-Poloxamer hydrogel in vitro was investigated
      as a function of C6S content in the graft copolymer by a spectrophotometric assay
      at 287 nm using an UV spectrophotometer. Differences in the adhesion and
      morphology of human lens cell between Poloxamer- and C6S-g-Poloxamer-coated
      surfaces were also investigated. The gelation temperatures of C6S-g-Poloxamer
      copolymers were lowered with increasing of the concentration of the copolymer and
      decreasing of C6S content. The release of ciprofloxacin from the graft copolymer
      was sustained compared with Poloxamer itself and decreased with increasing the
      content of C6S in the copolymer due to the in situ gel formation of the copolymer
      and viscous properties of C6S. Human lens cells (B3) adhered to C6S-g-Poloxamer
      coated surface were observed as transformed shapes after 2 days. The bioadhesive
      and thermally gelling of these graft copolymers will be expected to be an
      excellent drug carrier for the prolonged delivery to surface of the eye.

PMID- 16093212
TI  - Effect of simulated gastrointestinal conditions on drug release from
      pectin/ethylcellulose as film coating for drug delivery to the colon.
AB  - The aim of this work was to investigate the effect of acidic pH representative of
      gastric fluid on the release of 5-aminosalicylic acid from beads coated with
      pectin/ethylcellulose as film coating intended for drug delivery to the colon, in
      media mimicking the lower gastrointestinal (GI) tract and representative of
      colonic conditions. In this work, the in vitro incubation of the beads in acid
      medium was found to influence the hydration and the swelling characteristics of
      pectin after transfer into simulated intestinal fluid and simulated cecal fluid
      containing pectinolytic enzymes. Moreover, the drug release profiles from the
      beads in simulated intestinal fluid after incubation for 2 h or 30 min in
      simulated gastric fluid vs. no acid incubation were found to be very different.
      The in vitro degradation of pectin in the coat by pectinolytic enzymes in
      simulated cecal fluid depended on whether the beads were placed in simulated
      gastric fluid prior to testing in simulated intestinal fluid. The percentage drug
      release also depended on the ratio of pectin to ethylcellulose in the coat.

PMID- 16093214
TI  - Paclitaxel eluting stents for the treatment of angiographically non-significant
      atherosclerotic lesions.
AB  - OBJECTIVE: To assess the safety and efficacy of the implantation of Paclitaxel
      Eluting Stents (PES) for de novo, non-flow limiting lesions. METHODS AND RESULTS:
      We assessed the 12-month occurrence of major adverse cardiac events (MACE) in 21
      patients (4% of the total population treated in a 'real world' registry) with 22
      non-significant coronary narrowings treated with PES. The following criteria had
      to be met: (1) the lesion was de novo; (2) the location was non-ostial, and not a
      bifurcation lesion; (3) the diameter stenosis by quantitative coronary
      angiography (QCA) was <50%; (4) there was no visible thrombus and (5) the lesion
      was not located in an angiographically diffusely diseased segment. Procedural
      success rate was 100% without any periprocedural myocardial infarction. After a
      mean follow-up of 407.33+/-53 (range: 344-498) days the overall MACE-free
      survival was 95.2%. Freedom from target revascularization was 95.2%. CONCLUSIONS:
      The result of this non-randomized observational study suggests that the
      implantation of PES for de novo, non-significant lesions appears most probably
      safe and effective.

PMID- 16093215
TI  - Plaque sealing--a concept waiting for support.

PMID- 16093216
TI  - Detection of the vulnerable coronary atheromatous plaque. Where are we now?
AB  - Atherosclerosis is a progressive process with potentially devastating
      consequences and has been identified as the leading cause of morbidity and
      mortality, especially in the industrial countries. The underlying mechanisms
      include endothelial dysfunction, lipid accumulation and enhanced inflammatory
      involvement resulting in plaque disruption or plaque erosion and subsequent
      thrombosis. However, it has been made evident, that the majority of rupture prone
      plaques that produce acute coronary syndromes are not severely stenotic.
      Conversely, lipid-rich plaques with thin fibrous cap, heavily infiltrated by
      inflammatory cells have been shown to predispose to rupture and thrombosis,
      independently of the degree of stenosis. Therefore, given the importance of
      plaque composition, a continuously growing interest in the development and
      improvement of diagnostic modalities will promptly and most importantly,
      accurately detect and characterize the high-risk atheromatous plaque. Use of
      these techniques may help risk stratification and allow the selection of the most
      appropriate therapeutic approach.

PMID- 16093217
TI  - Safety of bivalirudin during percutaneous coronary interventions in patients with
      abnormal renal function.
AB  - BACKGROUND: Chronic kidney disease is associated with an increased risk of
      ischemic and bleeding complications after percutaneous coronary intervention
      (PCI). Bivalirudin, a direct thrombin inhibitor, has been shown to reduce adverse
      bleeding events compared to unfractionated heparin in patients undergoing PCI.
      However, the effect of diminished renal function on the safety and efficacy of
      bivalirudin for PCI is unknown. We aimed to test the safety of bivalirudin in
      routine practice and to assess whether this benefit was influenced by renal
      function. METHODS AND RESULTS: The interaction between renal impairment and
      benefit from bivalirudin was assessed in 115 consecutive patients (age 68.5+/
      12.1, 45% female) undergoing PCI. Bivalirudin dosing was adjusted based on renal
      function. Creatinine clearance (CrCl) was calculated using the Cockroft-Gault
      formula. The composite endpoints of in-hospital death, myocardial infarction or
      revascularization and bleeding events were assessed. Overall, these events
      occurred in 10 (8.7%) patients. Patients with a CrCl<60 ml/min had a
      significantly increased risk for in-hospital complications (18.6 versus 2.78%, P
      = 0.011). Univariate analysis for MACE and bleeding were significant for CrCl<60
      ml/min OR: 2.54 (95% CI: 1.61-39.7, P = 0.011), age OR: 3.29 (95% CI: 1.07-1.39,
      P<0.001) and female gender OR: 2.1 (95% CI: 0.036-0.89, P = 0.036). Risk of
      complications increased with decreasing renal function: 2.7, 14.2, and 37.5% for
      CrCl of >60, 30-60 or <30 ml/min, respectively, P = 0.002). CONCLUSION: Advanced
      age, renal dysfunction, and female gender remain important risk factors for
      ischemic and bleeding complications in patients undergoing PCI with bivalirudin.

PMID- 16093218
TI  - A comparison of the radial and the femoral approach in vein graft PCI. A
      retrospective study.
AB  - BACKGROUND: Transradial PCI is a safe and effective method of percutaneous
      revascularization. However, there is limited data on the efficacy of the
      transradial approach for saphenous vein graft (SVG) PCI. METHODS: We studied 334
      patients who underwent SVG PCI between January 2000 and December 2003, and
      compared the radial (132 patients) and the femoral (202 patients) approach.
      RESULTS: Mean EF (55.6+/-18.6% radial versus 58.1+/-16.8% femoral), lesion
      location (proximal, mid, distal: 22.6/50.6/26.7% versus 22.6/44.5/32.9%
      respectively) and lesion type (B1/B2/C: 3.4/4.1/92.5% versus 0.4/3.1/96.5%) were
      similar in both groups (P>0.05). Five patients had a failed radial attempt (3.8%)
      and were switched to the femoral approach. Mean fluoroscopy time (20.4+/-12.2
      versus 18.4+/-10.2 min), procedural time (60.0+/-27.2 versus 61.6+/-24.9 min) and
      the use of contrast (223+/-91 versus 234+/-91 ml) IIB/IIIA inhibitors (27.2
      versus 33.2%), and stenting (81.5 versus 81.3%) were similar in both groups,
      whereas 5 or 6 French sheaths were used more often in the radial group (83.4
      versus 64.9%, P<0.01). Angiographic success (93.9 versus 92.9%), in hospital MACE
      (radial:5 MI (3.8%) versus femoral: 1 death (0.5%) and 7 MI (3.5%) and major
      vascular complications (0.7 versus 0.5%) were also similar. CONCLUSIONS: The
      radial approach in SVG PCI is as fast and successful as the femoral.

PMID- 16093219
TI  - Clinical and angiographic outcome of stenting of unprotected left main coronary
      artery bifurcation narrowing.
AB  - PURPOSE: Improvements in techniques and equipments may result in the wider
      applicability of percutaneous coronary intervention (PCI) for unprotected left
      main coronary artery (ULMCA) stenosis. This report is a prospective study focused
      on the feasibility, effectiveness and long-term results of stenting for treatment
      of ULMCA bifurcation lesions. METHODS: From November 2002 to October 2003, 57
      consecutive patients were stented with bare metal stents and the technique of
      kissing balloon followed by T-provisional stenting was applied for ostial left
      anterior descending, left circumflex or distal left main coronary lesion.
      RESULTS: Mean age was 69.5+/-10.7 years. Acute coronary syndrome occurred in
      68.4% of patients with a majority of two or three vessel disease (45.10% and
      35.30% respectively). GpIIbIIIa inhibitors were used in only 5.8% of cases.
      Angiographic success was obtained in 100% of patients. Hospital stay was 7.03+/
      2.26 days without major adverse cardiac events. At eight months follow-up,
      cardiac death was 1.7%, non-fatal myocardial infarction 5.1% and target vessel
      revascularisation 22.8% including CABG 15.7% and repeated PCI 10.5% with an
      angiographic restenosis rate of 29.8%. CONCLUSION: In the setting of coronary
      stenting of the ULMCA stenosis, the use of bare metal stents can no longer be
      considered contemporary technique and another strategy such as coated stent may
      be needed.

PMID- 16093220
TI  - Discrepancy between morphologic and functional criteria of optimal stent
      deployment using intravascular ultrasound and pressure derived myocardial
      fractional flow reserve.
AB  - BACKGROUND: Pressure derived myocardial FFR, a functional index of epicardial
      stenosis has been proposed for the assessment of optimal stent deployment. The
      following study evaluated the potential of serial fractional flow reserve (FFR)
      measurements in comparison to the 'gold standard' intravascular ultrasound (IVUS)
      for optimal stent deployment and its long-term outcome. METHODS: 35 patients with
      a single de novo lesion underwent PTCA followed by stent implantation with an
      initial inflation pressure of 12 atm. If optimal stent expansion using IVUS
      criteria were not fulfilled, re-dilatation at 16 atm as well as additional
      inflations with larger balloon sizes were performed to reach the procedural end
      point. IVUS and FFR were performed after each dilatation (n = 136). Angiography
      was repeated after 6 months. RESULTS: In 30 pts who fulfilled IVUS criteria, mean
      lumen area (2.9+/-1.3 mm2) increased after PTCA and stent implantation to 10.0+/
      3.0 mm2. In six pts, optimum stent deployment according to a value of FFR0.94 was
      not reached. Four of six pts reached the IVUS criteria at 12 atm and two pts at
      16 atm, respectively. Positive and negative predictive values of FFR were 26 and
      64%. Three of the 30 pts (10%) revealed a restenosis at three months follow-up.
      One of these restenosis was seen in a patient with a post-procedural FFR<0.94.
      CONCLUSIONS: FFR was not valid to predict optimal stent expansion according to
      IVUS criteria but could delineate under-expanded stents despite a reasonable
      angiographic appearance. Morphologic (IVUS) and functional criteria (FFR) for
      optimal stent deployment revealed a comparably low restenosis rate.

PMID- 16093221
TI  - Multimodality imaging of borderline left main coronary disease using fluoroscopy,
      IVUS and CT coronary angiography.
AB  - A borderline left main narrowing was discovered during coronary angiography in a
      young asymptomatic man with positive stress test. IVUS demonstrated minimal
      diameter of 2.9 mm and the cross-sectional area was 11.5 mm(2). CTs were
      performed, and an eccentric calcific plaque was imaged at the ostium of the left
      main. Based on all three image modalities after discussing the different
      therapeutic options with the patient he was referred for bypass surgery.

PMID- 16093223
TI  - Subcortical dementia: historical review and personal view.

PMID- 16093224
TI  - Measuring health-related quality of life in patients with progressive
      supranuclear palsy.
AB  - The development of psychometrically sound health-related quality of life (Hr-QoL)
      instruments has made it possible to assess subjectively experienced Hr-QoL
      quantitatively, and to incorporate Hr-QoL as a measure in medical research and
      clinical trials. Hr-QoL in patients with progressive supranuclear palsy (PSP) has
      been measured using generic (not disease-specific) instruments, or Parkinson's
      disease-specific scales. We give an overview of the development of a disease
      specific Hr-QoL instrument for patients with PSP. Based on interviews with 27
      patients with PSP a preliminary Hr-QoL instrument was developed and administered
      to over 300 people with PSP in the UK and US. Following psychometric analysis a
      rating scale with a physical and a mental subscale emerged. In this patient
      sample, both subscales satisfied criteria for scaling assumptions, acceptability,
      reliability and validity (correlations with other measures consistent with a
      priori hypotheses). The psychometric properties of this questionnaire are
      undergoing further evaluation.

PMID- 16093225
TI  - Cognitive and behavioral aspects of PSP since Steele, Richardson and Olszewski's
      description of PSP 40 years ago and Albert's delineation of the subcortical
      dementia 30 years ago.
AB  - Although researchers are now familiar with progressive supranuclear palsy (PSP)
      and its characteristic "subcortical" dementia, this was not the case prior to
      seminal descriptions by Steele, Richardson, Olszewski and Albert. In fact, the
      first three authors identified this disorder, and the last one introduced the
      classification of the dementias according to the anatomical involvement. This
      paper is in honor of their contributions, and will also outline the changes that
      have occurred since their seminal works.

PMID- 16093226
TI  - Limb apraxia and cognitive impairment in progressive supranuclear palsy.
AB  - Limb apraxia occurs in progressive supranuclear palsy (PSP); however, its
      characteristics and relation to dementia are unclear. We compared 25 probable PSP
      patients on cognitive and ideomotor apraxia tests with 19 healthy controls.
      Eleven PSP patients were demented (D-PSP) and 14 not (ND-PSP). D-PSP patients did
      worse than controls and ND-PSP patients in all cognitive tests; and ND-PSP
      patients did worse than controls in all except the memory test. In the apraxia
      test, PSP patients committed mainly sequence errors and executed complex gestures
      badly. Apraxia correlated strongly with dementia. In PSP, limb apraxia seems
      mainly due to frontal deafferentation and lesions, but only when these are severe
      enough to cause dementia.

PMID- 16093227
TI  - Subcortical dementia revisited: similarities and differences in cognitive
      function between progressive supranuclear palsy (PSP), corticobasal degeneration
      (CBD) and multiple system atrophy (MSA).
AB  - To examine the similarities and differences in cognitive function between three
      predominantly subcortical dementing disorders associated with parkinsonism we
      compared the profiles of cognitive performance in 39 patients with Progressive
      Supranuclear Palsy (PSP), 26 patients with Multiple System Atrophy (MSA) and 25
      with Corticobasal Degeneration (CBD) with those of 30 patients with classic
      cortical dementia, Alzheimer's Disease (AD), using two different cognitive
      screening tests: Dementia Rating Scale (DRS) and Addenbrooke's Cognitive
      Examination (ACE). The cognitive profile on ACE and DRS subtests distinguished
      subcortical diseases from each other as well as from AD. All parkinsonian
      syndromes were characterized by a disproportionate impairment in verbal fluency,
      particularly letter fluency. The three diseases differed, however, in the degree
      of language, memory and visuospatial impairment. We conclude that similarities,
      as well as differences, between PSP, MSA and CBD can be detected using a brief,
      clinically applicable cognitive screening test. The pattern of cognitive
      impairment is likely to reflect a different distribution of pathology, in
      particular a higher degree of cortical involvement in PSP and CBD.

PMID- 16093228
TI  - Can the frontal assessment battery (FAB) differentiate bradykinetic rigid
      syndromes? Relation of the FAB to formal neuropsychological testing.
AB  - The frontal assessment battery (FAB) is a bedside test of executive function. It
      takes less than 10 minutes to administer and a low score indicates executive
      dysfunction. To determine whether the FAB could detect the more severe
      subcortical dementia that is a feature of PSP and differentiate it from other
      bradykinetic rigid syndromes, we studied 17 patients with progressive
      supranuclear palsy (PSP); 11 with multiple system atrophy (MSA) and 12 with
      Parkinson's disease (PD). We compared FAB scores with the results of more
      detailed tests of executive and general cognitive function.FAB scores were
      significantly lower in PSP than in MSA or PD (p=0.02 and p<0.001) and were also
      found to be significantly lower in MSA than in PD (p=0.047). We divided the study
      group into those with an FAB score <15 and those with an FAB score>/=5,
      regardless of the clinical diagnosis. While 82% of the PSP group had FAB scores
      of <15, such scores were recorded in only 36% of the MSA and 8% of the PD groups.
      The lexical fluency and motor series subscores of the FAB discriminated 70% of
      the PSP, MSA and PD patients. The FAB scores correlated with tests of executive
      function, as well as with scores on the Mattis Dementia Rating Scale, the Mini
      Mental State Examination and other tests of general cognitive function. A
      stepwise regression analysis revealed that across the groups, among the variables
      that correlated with FAB scores, alternating semantic fluency accounted for 80%
      of FAB variance.These results suggest that the FAB is a valid and easily
      applicable bedside test to discriminate executive dysfunction in these three
      frequently confused bradykinetic rigid syndromes.

PMID- 16093229
TI  - Atypical progressive supranuclear palsy underlying progressive apraxia of speech
      and nonfluent aphasia.
AB  - Progressive supranuclear palsy (PSP) is a clinicopathological entity typically
      presenting as an akinetic rigid syndrome with early falls, axial rigidity,
      vertical supranuclear gaze palsy and levodopa resistance. Pathological features
      consist of tau deposition in neuronal and glial cells located mainly in
      subcortical and brainstem structures. Rare cases with the pathological diagnosis
      of atypical PSP have been described in which neocortical tau deposition is more
      widespread than what is usually seen in typical PSP. Progressive nonfluent
      aphasia (PNFA) is a syndrome characterized by spontaneous nonfluent speech and
      early preserved comprehension of language. Apraxia of speech (AOS) is a motor
      speech disorder that may be a feature of PNFA. We report the clinical and
      pathological findings of four cases that presented with features most consistent
      with PNFA predominated by AOS. Pathological features in these four cases included
      the typical features of PSP subcortically and in brainstem structures, but
      combined with tau-positive neuronal and glial pathology in the neocortex.
      Comprehensive semiquantitative analyses of tau burden including neurofibrillary
      tangles and pretangles, coiled bodies, tufted astrocytes and threads were
      undertaken in the four cases of atypical PSP and compared to 10 cases of typical
      PSP. Semiquantitative analysis demonstrated that in atypical PSP, the pathology
      shifts from subcortical grey and brainstem regions, commonly affected in typical
      PSP, towards neocortical regions. This shift in pathology accounts for the
      presentation of PNFA and AOS observed in our patients, as well as the lack of
      classic features of PSP. These cases demonstrate that atypical PSP can present as
      AOS and PNFA without the classic features of PSP.

PMID- 16093231
TI  - Safety assurances for dietary supplements policy issues and new research
      paradigms.
AB  - Herbal therapies are used by more than 12% of the U.S. population each year,
      resulting in annual out-of-pocket expenses above $5 billion. Utilization rates
      are particularly high among patients with chronic diseases, and in patients
      frequently seen in clinic by physicians and nurse practitioners. Most physicians
      do not receive formal education regarding the safety of these therapies, and
      there is growing concern in the medical community about the potential risks to
      patients and the paucity of reliable information. Numerous adverse effects and
      interactions have been attributed to dietary supplements, based on variable
      levels of evidence ranging from historical use or anecdotes to pre-clinical
      research or high-quality clinical trials. Significant potential morbidity and
      costs have been indirectly associated with herb/supplement-drug interactions,
      including increased emergency room visits, outpatient clinic visits, and
      perioperative complications. However, most research has focused on efficacy
      rather than safety. Post-market surveillance is complicated by the uneven
      standardization of products between manufacturers, and in some cases between
      batches produced by the same manufacturer. To assure public safety around the use
      of dietary supplements within the framework of existing legislation and market
      realities, schema must evolve to more systematically monitor the safety of agents
      in the post-market environment; identify potentially dangerous supplements
      (and/or constituents); study the mechanism and potential hazards of these
      identified products; and clarify the process by which products may be considered
      for removal from the market. We discuss research and educational paradigms within
      this context which make use of existing surveillance mechanisms to more
      efficiently identify agents of particular concern. Specific examples are given.

PMID- 16093232
TI  - A preliminary investigation of the enzymatic inhibition of 5alpha-reduction and
      growth of prostatic carcinoma cell line LNCap-FGC by natural astaxanthin and Saw
      Palmetto lipid extract in vitro.
AB  - Inhibition of 5alpha-reductase has been reported to decrease the symptoms of
      benign prostate hyperplasia (BPH) and possibly inhibit or help treat prostate
      cancer. Saw Palmetto berry lipid extract (SPLE) is reported to inhibit 5alpha
      reductase and decrease the clinical symptoms of BPH. Epidemiologic studies report
      that carotenoids such as lycopene may inhibit prostate cancer. In this
      investigation the effect of the carotenoid astaxanthin, and SPLE were examined
      for their effect on 5alpha-reductase inhibition as well as the growth of
      prostatic carcinoma cells in vitro. These studies support patent #6,277,417 B1.
      The results show astaxanthin demonstrated 98% inhibition of 5alpha-reductase at
      300 microg/mL in vitro. Alphastat, the combination of astaxanthin and SPLE,
      showed a 20% greater inhibition of 5alpha-reductase than SPLE alone n vitro. A
      nine day treatment of prostatic carcinoma cells with astaxanthin in vitro
      produced a 24% decrease in growth at 0.1 mcg/mL and a 38% decrease at 0.01
      mcg/mL. SPLE showed a 34% decrease at 0.1 mcg/mL. CONCLUSIONS: Low levels of
      carotenoid astaxanthin inhibit 5alpha-reductase and decrease the growth of human
      prostatic cancer cells in vitro. Astaxanthin added to SPLE shows greater
      inhibition of 5alpha-reductase than SPLE alone in vitro.

PMID- 16093233
TI  - Hypoglycemic potencies of crude ethanolic extracts of cashew roots and unripe
      pawpaw fruits in guinea pigs and rats.
AB  - Adult guinea pigs and albino rats were given 2 mg/100 g-body weight of crude
      ethanolic extract of cashew root or pawpaw fruits, thereafter, tail blood films
      were collected to monitor postprandial glucose levels, thereafter, animals were
      thereafter maintained at 2 mg/ 100 g-body weight of extract 3 times daily for
      seven days. Organ body weight ratios and biochemical parameters in the plasma
      were determined. The crude ethanolic extract of cashew root and pawpaw fruits
      showed hypoglycemic potencies, however, the crude ethanolic extract of cashew
      roots showed more hypoglycemic potency than the crude extract of pawpaw fruits in
      both guinea pigs and rats. The ethanolic extracts reduced both plasma glucose as
      well as cholesterol and total lipids but showed no effect on plasma protein;
      pawpaw extract reduced glucose, liver glycogen, cholesterol and total lipid in
      guinea pigs from 46.50 +/- 3.50-14.30 +/- 0.29 (mg/dl), 5.51 +/- 1.5-1.52 +/-
      0.50 (g/100 g); 189.09 +/- 5.91-162.50 +/- 2.95 (mg/dl); 705.00 +/- 46.06-630.00
      +/- 15.06 (mg/dl), respectively; while in rats reductions were from 53.3 +/- 3.50
      32.25 +/- 3.25 (mg/dl), 4.28 +/- 0.50-2.3 +/- 0.78 (g/100 g); 203.85 +/- 2.95
      171.23 +/- 5.78 (mg/dl) and 855.00 +/- 45.0-645.00 +/- 30.0 (mg/dl),
      respectively. Cashew extract reduced the same parameters in guinea pig from 46.50
      +/- 3.50-7.00 +/- 0.10 (mg/dl); 5.51 +/- 1.5-0.15 +/- 0.50 (g/100 g); 189.09 +/-
      5.91-162.50 +/- 0.04 (mg/dl) and 705.00 +/- 45.06-562.50 +/- 52.5 5.91-162.50 +/-
      0.04 (mg/dl) and 705.00 +/- 45.06-562.50 +/- 52.5 (mg/dl). The reduction in rats
      were from 53.5 +/- 3.50-10.75 +/- 3.75 (mg/dl); 4.28 +/- 0.50-0.18 +/- 0.30
      (g/100 g); 203.85 +/- 2.95-162.50 +/- 8.06 (mg/dl) and 855.00 +/- 45.0-557.50 +/-
      37.5 (mg/dl), respectively. The work concludes that ethanolic extract of cashew
      root and pawpaw fruit contains natural substances that can be harnessed for the
      treatment and management of diabetes mellitus.

PMID- 16093234
TI  - Phenolic acids in neem (Azadirachta indica): a major pre-existing secondary
      metabolites.
AB  - High Performance Liquid Chromatographic (HPLC) analyses of various parts (fresh
      and dry bark of stem, mature and tender leaves, flower and different parts of
      fruit, i.e., raw and ripe fruit epicarp, mesocarp and seed) of neem (Azadirachta
      indica), which occupies an important place in socio-cultural-religious life in
      Indian communities, indicate that neem is rich in pre-existing secondary
      metabolites (phenolic acids). Dry bark showed only tannic acid but in fresh bark
      three phenolic acids were observed, i.e., gallic, tannic, and ferulic acids. In
      tender leaves only gallic and ferulic acids were detected, but the levels of
      these phenolic acids in mature leaves were about three times and fifty times
      greater, respectively. Flowers had only two phenolic acids in which gallic acid
      was maximum followed by chlorogenic acid. The level of phenolic acid was maximum
      in seeds followed by epicarp and pulp. In raw and ripe fruit seeds four phenolic
      acids were detected. Raw fruit seeds were rich in phenolic acids than ripe fruit
      seeds. Fruit epicarp was relatively richer than seed, seed pulp and flowers of
      the plants. Neem flowers were also rich in gallic and chlorogenic acids.

PMID- 16093235
TI  - Screening of some medicinal plants used in south-west Nigerian traditional
      medicine for anti-Salmonella typhi activity.
AB  - Ten Nigerian medicinal plants used traditionally for the treatment of several
      ailments of both microbial and non-microbial origins were tested on multi-drug
      resistant S. typhi (MDR) strains of which six of them were active. The results
      revealed that both the aqueous and ethanol extracts of Terminalia avicennioides,
      Momordica balsamina, Combretum paniculatum and Trema guineensis were effective on
      the MDR-S. typhi strains with minimum inhibitory concentration (MIC) and minimum
      bactericidal concentration (MBC) values ranging from 9.60 to 14 mcg/ml and 24 to
      33 mcg/ml, respectively. Whereas, only the aqueous extracts of Morinda lucida and
      Ocimum gratissimum were found to be active against this pathogen with MIC and MBC
      values of 9.60 and 24 mcg/ml for M. lucida, 40 and 55 mcg/ml for O. gratissimum,
      respectively. There was no statistical significant difference (P > 0.05) between
      the activity of each plant extract and the decoctions prepared from them. All the
      six active plants showed positive reactions to alkaloids, tannins, flavonoids and
      anthraquinones but in variable degrees. All but M. balsamina, indicated the
      presence of saponin.

PMID- 16093236
TI  - The assessment of biological activities associated with the major constituents of
      the methanol extract of 'wild carrot' (Daucus carota L) seeds.
AB  - Daucus carota L. (Family: Apiaceae alt. Umbelliferae), commonly known as 'wild
      carrot' or 'Queen Anne's-lace,' is an ecologically invasive erect biennial
      naturalized to Scotland. The ethnobotanical uses of this species include
      applications in the treatment of cough, diarrhea, dysentery, cancer, malaria and
      tumors, and as an antiseptic, abortifacient, aphrodisiac, carminative, stimulant,
      stomachic and tonic. The major constituents isolated from the methanol extract of
      D. carota seeds by reversed-phase preparative high performance chromatography
      were luteolin, luteolin 3'-O-beta-D-glucopyranoside and luteolin 4'-O-beta-D
      glucopyranoside, three flavones. The constituents were assessed for their
      antibacterial and free radical scavenging activities, as well as toxicity towards
      brine shrimp. Among these three flavones, luteolin showed the highest degree of
      free radical scavenging activity (RC50 = 4.3 x 10(-4) mg/mL) in the 2,2-diphenyl
      1-picrylhydrazyl (DPPH) assay. Both luteolin and its 4'-O-glucoside demonstrated
      bactericidal activity against Staphylococcus aureus and Escherichia coli (Minimum
      Inhibitory Concentration [MIC] = 5.0 x 10(-2) - 1.0 x 10(-1) mg/mL). Luteolin
      also demonstrated antibactericidal activity against Bacillus cereus and
      Citrobacter freundii (MIC = 5.0 x 10(-2) mg/mL). Luteolin 3'-O-glucoside showed
      bactericidal activity against Bacillus cereus and Lactobacillus plantarum (MIC =
      2.5 x 10(-1) mg/mL and 5 x 10(-1) mg/ mL, respectively). In the brine shrimp
      lethality assay, the LD50 value of luteolin was 5.3 x 10(-2) mg/mL, and that of
      its 3'-O-glucoside and 4'-O-glucoside were > 1.0 mg/mL.

PMID- 16093237
TI  - Dosing botanical medicines.

PMID- 16093238
TI  - Evidence-based systematic review of dandelion (Taraxacum officinale) by natural
      standard research collaboration.

PMID- 16093239
TI  - Crystal structure and functional analysis of lipoamide dehydrogenase from
      Mycobacterium tuberculosis.
AB  - We report the 2.4 A crystal structure for lipoamide dehydrogenase encoded by lpdC
      from Mycobacterium tuberculosis. Based on the Lpd structure and sequence
      alignment between bacterial and eukaryotic Lpd sequences, we generated single
      point mutations in Lpd and assayed the resulting proteins for their ability to
      catalyze lipoamide reduction/oxidation alone and in complex with other proteins
      that participate in pyruvate dehydrogenase and peroxidase activities. The results
      suggest that amino acid residues conserved in mycobacterial species but not
      conserved in eukaryotic Lpd family members modulate either or both activities and
      include Arg-93, His-98, Lys-103, and His-386. In addition, Arg-93 and His-386 are
      involved in forming both "open" and "closed" active site conformations,
      suggesting that these residues play a role in dynamically regulating Lpd
      function. Taken together, these data suggest protein surfaces that should be
      considered while developing strategies for inhibiting this enzyme.

PMID- 16093240
TI  - Crystal structure of SmcL, a bacterial neutral sphingomyelinase C from Listeria.
AB  - Sphingomyelinases C are enzymes that catalyze the hydrolysis of sphingomyelin in
      biological membranes to ceramide and phosphorylcholine. Various pathogenic
      bacteria produce secreted neutral sphingomyelinases C that act as membrane
      damaging virulence factors. Mammalian neutral sphingomyelinases C, which display
      sequence homology to the bacterial enzymes, are involved in sphingolipid
      metabolism and signaling. This article describes the first structure to be
      determined for a member of the neutral sphingomyelinase C family, SmcL, from the
      intracellular bacterial pathogen Listeria ivanovii. The structure has been
      refined to 1.9-A resolution with phases derived by single isomorphous replacement
      with anomalous scattering techniques from a single iridium derivative. SmcL
      adopts a DNase I-like fold, and is the first member of this protein superfamily
      to have its structure determined that acts as a phospholipase. The structure
      reveals several unique features that adapt the protein to its phospholipid
      substrate. These include large hydrophobic beta-hairpin and hydrophobic loops
      surrounding the active site that may bind and penetrate the lipid bilayer to
      position sphingomyelin in a catalytically competent position. The structure also
      provides insight into the proposed general base/acid catalytic mechanism, in
      which His-325 and His-185 play key roles.

PMID- 16093241
TI  - Identification of MMP-15 as an anti-apoptotic factor in cancer cells.
AB  - We have performed an in vitro selection for an anti-apoptotic phenotype that
      resembles the selection process that pre-malignant cells undergo in the initial
      phase of carcinogenesis in vivo. Using the cervical carcinoma cell line HeLa S3
      as a model system, the selection procedure yielded cell clones that displayed
      increased resistance to apoptosis induced by Fas, tumor necrosis factor-related
      apoptosis-inducing ligand, and serum starvation. Gene expression profiling using
      gene family focused cDNA arrays revealed numerous genes that are differentially
      expressed in HeLa S3 and the resistant subclones and therefore are potentially
      involved in the definition of sensitivity to apoptotic stimuli. From the genes
      identified in this functional genomics approach we validated the anti-apoptotic
      activity of the membrane-anchored matrix metalloproteinase 15 (MMP-15) by means
      of small interfering RNA-mediated knock-down and ectopic expression in parental
      HeLa S3 cells and, to confirm a more general significance of our findings, in
      other cancer cell lines. The in vivo relevance of these findings is supported by
      the overexpression of MMP-15 in human lung adenocarcinoma compared with normal
      lung. Because MMP-15 is known to promote invasion, our results suggest that this
      protease connects metastasis and apoptosis resistance by an unknown regulatory
      mechanism. Our findings therefore strongly suggest that cancer characteristics
      such as metastatic potential, which are thought to evolve late in cancer
      progression, could be manifested early on by selection for an anti-apoptotic
      phenotype.

PMID- 16093242
TI  - Identification of mammalian proteins cross-linked to DNA by ionizing radiation.
AB  - Ionizing radiation (IR) is an important environmental risk factor for various
      cancers and also a major therapeutic agent for cancer treatment. Exposure of
      mammalian cells to IR induces several types of damage to DNA, including double-
      and single-strand breaks, base and sugar damage, as well as DNA-DNA and DNA
      protein cross-links (DPCs). Little is known regarding the biological consequences
      of DPCs. Identifying the proteins that become cross-linked to DNA by IR would be
      an important first step in this regard. We have therefore undertaken a proteomics
      study to isolate and identify proteins involved in IR-induced DPCs. DPCs were
      induced in AA8 Chinese hamster ovary or GM00637 human fibroblast cells using 0-4
      gray of gamma-rays under either aerated or hypoxic conditions. DPCs were isolated
      using a recently developed method, and proteins were identified by mass
      spectrometry. We identified 29 proteins as being cross-linked to DNA by IR under
      aerated and/or hypoxic conditions. The identified proteins include structural
      proteins, actin-associated proteins, transcription regulators, RNA-splicing
      components, stress-response proteins, cell cycle regulatory proteins, and GDP/GTP
      binding proteins. The involvement of several proteins (actin, histone H2B, and
      others) in DPCs was confirmed by using Western blot analysis. The dose
      responsiveness of DPC induction was examined by staining one-dimensional SDS
      polyacrylamide gels with SYPRO Tangerine followed by analysis using fluorescence
      imaging. Quantitation of the fluorescence signal indicated no significant
      difference in total yields of IR-induced DPCs generated under aerated or hypoxic
      conditions, although differences were observed for several individual protein
      bands.

PMID- 16093243
TI  - Down-regulation of factor IXa in the factor Xase complex by protein Z-dependent
      protease inhibitor.
AB  - Protein Z-dependent protease inhibitor (ZPI) is a serpin inhibitor of coagulation
      factor (F) Xa dependent on protein Z, Ca2+, and phospholipids. In new studies,
      ZPI inhibited FIXa in the FXase complex. Since this observation could merely
      represent inhibition of the FXa product whose activity was measured, inhibition
      of FIXa was investigated five ways. 1) FXase incubation mixtures with/without
      ZPI/protein Z were diluted in EDTA; FXa activity was measured after reversal of
      its inhibition. 2) FXase incubation mixtures were immunoblotted for FXa product.
      3) FX activation peptide region was 3H-labeled; release of 3H was used to measure
      FXase activity. 4) Activity was monitored in a FIXa-based clotting assay. 5) FIXa
      amidolytic activity was measured. In all cases, FIXa was inhibited by
      subphysiologic levels of ZPI. Unlike inhibition of FXa, inhibition of FIXa did
      not strictly require protein Z. Low concentrations of FVIIIa increased the
      efficiency of ZPI inhibition of FIXa; FVIIIa in molar excess was not protective
      of FIXa unless FIXa/FVIIIa interacted prior to ZPI exposure. Unusual time courses
      were observed for inhibition of both FIXa in the FXase complex and FXa in the
      prothrombinase complex. Activity loss stabilized in <100 s at a level dependent
      on ZPI concentration, suggesting equilibrium interactions rather than typical
      covalent serpin-protease interactions. Surface plasmon resonance binding
      experiments revealed binding and dissociation of ZPI/FIXa with Kd (app) of 9-12
      nm, similar to the concentration of ZPI needed for 50% inhibition. ZPI may be an
      unusual physiologic regulator of both the intrinsic FXase and the prothrombinase
      complexes.

PMID- 16093244
TI  - The DNA-dependent protein kinase catalytic subunit phosphorylation sites in human
      Artemis.
AB  - Artemis protein has irreplaceable functions in V(D)J recombination and
      nonhomologous end joining (NHEJ) as a hairpin and 5' and 3' overhang
      endonuclease. The kinase activity of the DNA-dependent protein kinase catalytic
      subunit (DNA-PKcs) is necessary in activating Artemis as an endonuclease. Here we
      report that three basal phosphorylation sites and 11 DNA-PKcs phosphorylation
      sites within the mammalian Artemis are all located in the C-terminal domain. All
      but one of these phosphorylation sites deviate from the SQ or TQ motif of DNA
      PKcs that was predicted previously from in vitro phosphorylation studies.
      Phosphatase-treated mammalian Artemis and Artemis that is mutated at the three
      basal phosphorylation sites still retain DNA-PKcs-dependent endonucleolytic
      activities, indicating that basal phosphorylation is not required for the
      activation. In vivo studies of Artemis lacking the C-terminal domain have been
      reported to be sufficient to complement V(D)J recombination in Artemis null
      cells. Therefore, the C-terminal domain may have a negative regulatory effect on
      the Artemis endonucleolytic activities, and phosphorylation by DNA-PKcs in the C
      terminal domain may relieve this inhibition.

PMID- 16093245
TI  - Substrate-induced conformational changes in the membrane-embedded IIC(mtl)-domain
      of the mannitol permease from Escherichia coli, EnzymeII(mtl), probed by
      tryptophan phosphorescence spectroscopy.
AB  - Membrane-bound transport proteins are expected to proceed via different
      conformational states during the translocation of a solute across the membrane.
      Tryptophan phosphorescence spectroscopy is one of the most sensitive methods used
      for detecting conformational changes in proteins. We employed this technique to
      study substrate-induced conformational changes in the mannitol permease,
      EnzymeII(mtl), of the phosphoenolpyruvate-dependent phosphotransferase system
      from Escherichia coli. Ten mutants containing a single tryptophan were engineered
      in the membrane-embedded IIC(mtl)-domain, harboring the mannitol translocation
      pathway. The mutants were characterized with respect to steady-state and time
      resolved phosphorescence, yielding detailed, site-specific information of the Trp
      microenvironment and protein conformational homogeneity. The study revealed that
      the Trp environments vary from apolar, unstructured, and flexible sites to
      buried, highly homogeneous, rigid peptide cores. The most remarkable example of
      the latter was observed for position 97, because its long sub-second
      phosphorescence lifetime and highly structured spectra in both glassy and fluid
      media imply a well defined and rigid core around the probe that is typical of
      beta-sheet-rich structural motifs. The addition of mannitol had a large impact on
      most of the Trp positions studied. In the case of position 97, mannitol binding
      induced partial unfolding of the rigid protein core. On the contrary, for residue
      positions 126, 133, and 147, both steady-state and time-resolved data showed that
      mannitol binding induces a more ordered and homogeneous structure around these
      residues. The observations are discussed in context of the current mechanistic
      and structural model of EII(mtl).

PMID- 16093246
TI  - Identification of an agonist-induced conformational change occurring adjacent to
      the ligand-binding pocket of the M(3) muscarinic acetylcholine receptor.
AB  - To study the conformational changes that convert G protein-coupled receptors
      (GPCRs) from their resting to their active state, we used the M(3) muscarinic
      acetylcholine receptor, a prototypical class A GPCR, as a model system.
      Specifically, we employed a recently developed in situ disulfide cross-linking
      strategy that allows the formation of disulfide bonds in Cys-substituted mutant
      M(3) muscarinic receptors present in their native membrane environment. At
      present, little is known about the conformational changes that GPCR ligands
      induce in the immediate vicinity of the ligand-binding pocket. To address this
      issue, we generated 11 Cys-substituted mutant M(3) muscarinic receptors and
      characterized these receptors in transfected COS-7 cells. All analyzed mutant
      receptors contained an endogenous Cys residue (Cys-532(7.42)) located within the
      exofacial segment of transmembrane domain (TM) VII, close to the agonist-binding
      site. In addition, all mutant receptors harbored a second Cys residue that was
      introduced into the exofacial segment of TM III, within the sequence Leu
      142(3.27)-Asn-152(3.37). Disulfide cross-linking studies showed that muscarinic
      agonists, but not antagonists, promoted the formation of a disulfide bond between
      S151(3.36)C and Cys-532. A three-dimensional model of the inactive state of the
      M(3) muscarinic receptor indicated that Cys-532 and Ser-151 face each other in
      the center of the TM receptor core. Our cross-linking data therefore support the
      concept that agonist activation pulls the exofacial segments of TMs VII and III
      closer to each other. This structural change may represent one of the early
      conformational events triggering the more pronounced structural reorganization of
      the intracellular receptor surface. To the best of our knowledge, this is the
      first direct demonstration of a conformational change occurring in the immediate
      vicinity of the binding site of a GPCR activated by a diffusible ligand.

PMID- 16093247
TI  - Suppression of death receptor-mediated apoptosis by 1,25-dihydroxyvitamin D3
      revealed by microarray analysis.
AB  - Recent studies suggest that growth inhibition by 1,25-dihydroxyvitamin D3
      represents an innovative approach to ovarian cancer therapy. To understand the
      molecular mechanism of 1,25-dihydroxyvitamin D3 action, we profiled the hormone
      induced changes in the transcriptome of ovarian cancer cells using microarray
      technology. More than 200 genes were identified to be regulated by 1,25
      dihydroxyvitamin D3. Reverse transcription-PCR analyses confirmed the regulation
      of a group of apoptosis-related genes, including the up-regulation of the decoy
      receptor that inhibits tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) action, TRAIL receptor 4, and the down-regulation of Fas, the receptor
      that mediates the action of Fas ligand. The regulation was further confirmed at
      the protein level. Consistent with the regulation of the death receptors,
      pretreatment with 1,25-dihydroxyvitamin D3 decreased apoptosis induced by TRAIL
      and Fas ligand. Because persistent 1,25-dihydroxyvitamin D3 treatment has been
      shown to induce apoptosis in ovarian cancer, the hormone appears to exert a dual
      effect on the death of ovarian cancer cells. Knockdown of TRAIL receptor 4 by RNA
      interference or ectopic expression of Fas relieved the suppressive effect of 1,25
      dihydroxyvitamin D3, showing that molecular manipulation of death receptors is a
      viable approach to overcome the protective effect of 1,25-dihydroxyvitamin D3 on
      the apoptosis of ovarian cancer. These strategies may allow ovarian cancer
      patients to benefit from therapy with both 1,25-dihydroxyvitamin D3 and ligands
      for death receptors, such as TRAIL, shown to selectively induce apoptosis in
      cancer but not normal cells.

PMID- 16093248
TI  - Sphingosine kinase 2 is required for modulation of lymphocyte traffic by FTY720.
AB  - Immunotherapeutic drugs that mimic sphingosine 1-phosphate (S1P) disrupt
      lymphocyte trafficking and cause T helper and T effector cells to be retained in
      secondary lymphoid tissue and away from sites of inflammation. The prototypical
      therapeutic agent, 2-alkyl-2-amino-1,3-propanediol (FTY720), stimulates S1P
      signaling pathways only after it is phosphorylated by one or more unknown
      kinases. We generated sphingosine kinase 2 (SPHK2) null mice to demonstrate that
      this kinase is responsible for FTY720 phosphorylation and thereby its subsequent
      actions on the immune system. Both systemic and lymphocyte-localized sources of
      SPHK2 contributed to FTY720 induced lymphopenia. Although FTY720 was selectively
      activated in vivo by SPHK2, other S1P pro-drugs can be phosphorylated to cause
      lymphopenia through the action of additional sphingosine kinases. Our results
      emphasize the importance of SPHK2 expression in both lymphocytes and other
      tissues for immune modulation and drug metabolism.

PMID- 16093249
TI  - Early growth response gene 1 (EGR1) regulates heparanase gene transcription in
      tumor cells.
AB  - Heparanase is an endoglycosidase that degrades heparan sulfate chains of heparan
      sulfate proteoglycans, a key component of extracellular matrix and basement
      membranes. Studies using heparanase inhibitors and gene silencing have provided
      evidence to support an important role for heparanase in tumor metastasis and
      angiogenesis. The expression of heparanase is normally very tightly controlled,
      however, it is commonly deregulated in tumor cells, which express elevated
      heparanase activity that correlates with high levels of heparanase mRNA. We
      recently identified the transcription factor early growth response gene 1, EGR1,
      as a key regulator of inducible heparanase transcription in T cells. In this
      study using chromatin immunoprecipitation, we demonstrate for the first time that
      EGR1 binds to the heparanase gene promoter in vivo. The important question of the
      role of EGR1 in regulating heparanase transcription in tumor cells was then
      assessed. Studies were carried out in four epithelial tumor lines of different
      tissue origin. Functional dissection of the heparanase promoter identified a 280
      bp region that was critical for transcription of the heparanase gene.
      Transactivation studies using an EGR1 expression vector co-transfected with a
      reporter construct containing the 280-bp region showed EGR1-activated heparanase
      promoter activity in a dose-dependent manner in prostate or breast adenocarcinoma
      and colon carcinoma cell lines. In contrast, overexpression of EGR1 resulted in a
      dose-dependent repression of promoter activity in melanoma cells. Using site
      directed mutagenesis the 280-bp region was found to contain two functional EGR1
      sites and electrophoretic mobility shift assays showed binding of EGR1 to both of
      these sites upon activation of tumor cells. Furthermore, the heparanase promoter
      region containing the EGR1 sites was also inducible in tumor cells and induction
      corresponded to HPSE expression levels. These studies show that EGR1 regulates
      heparanase transcription in tumor cells and importantly, can have a repressive or
      activating role depending on the tumor type.

PMID- 16093250
TI  - Modulation of arachidonic acid metabolism and nitric oxide synthesis by garcinol
      and its derivatives.
AB  - Garcinol, a polyisoprenylated benzophenone, from the fruit rind of Garcinia spp.,
      has been shown to have anti-inflammatory and anticarcinogenic activities. To
      study its mechanism of action, we analyzed the effects of garcinol and its
      derivatives, including cambogin, garcim-1 and garcim-2, on arachidonic acid
      metabolism and nitric oxide (NO) synthesis in lipopolysaccharide (LPS)-stimulated
      RAW264.7 murine macrophages as well as in three intestinal cell lines. We also
      examined the effect of garcinol on cytosolic phospholipase A2 (cPLA2),
      cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), and related upstream
      signaling. At 1 microM, garcinol and its derivatives, added 1 h after LPS
      stimulation, significantly inhibited the release of arachidonic acid and its
      metabolites in macrophages; garcinol was the most effective, showing >50%
      inhibition. Similar inhibitory activity was also observed in intestinal cells, HT
      29, HCT-116 and IEC-6 cells, showing 40-50% inhibition by 1 microM garcinol. In
      LPS-stimulated macrophages, garcinol inhibited the phosphorylation of cPLA2
      without altering its protein level, and the effect was related to the inhibition
      of ERK1/2 phosphorylation. Garcinol inhibited NFkappaB activation and COX-2
      expression only when it was added to the cells before LPS stimulation. Garcinol
      (1 microM) also significantly decreased iNOS expression and NO release from LPS
      stimulated macrophages; this is probably due to the inhibition of the signal
      transducer and activator of transcription-1 (STAT-1), an upstream event in the
      activation of iNOS synthesis. The results suggest that garcinol modulates
      arachidonic acid metabolism by blocking the phosphorylation of cPLA2 and
      decreases iNOS protein level by inhibiting STAT-1 activation. These activities
      may contribute to the anti-inflammatory and anticarcinogenic actions of garcinol
      and its derivatives.

PMID- 16093251
TI  - Evidence for complex multigenic inheritance of radiation AML susceptibility in
      mice revealed using a surrogate phenotypic assay.
AB  - The mapping of genes which affect individual cancer risk is an important but
      complex challenge. A surrogate assay of susceptibility to radiation-induced acute
      myeloid leukaemia (AML) in the mouse based on chromosomal radiosensitivity has
      been developed and validated. This assay was applied to the mapping of radiation
      induced AML risk modifier loci by association with microsatellite markers. A
      region on chromosome (chr) 18 with strong association is identified and confirmed
      by backcross analysis. Additional loci on chrs 8 and 13 show significant
      association. A key candidate gene Rbbp8 on chr18 is identified. Rbbp8 is shown to
      be upregulated in response to X-irradiation in the AML sensitive CBA strain but
      not AML resistant C57BL/6 strain. This study demonstrates the strength of
      utilizing surrogate endpoints of cancer susceptibility in the mapping of mouse
      loci and identifies additional loci that may affect radiation cancer risk.

PMID- 16093252
TI  - Cognitive behaviour therapy in addition to antispasmodic treatment for irritable
      bowel syndrome in primary care: randomised controlled trial.
AB  - OBJECTIVE: To assess the efficacy of cognitive behaviour therapy delivered in
      primary care for treating irritable bowel syndrome. DESIGN: Randomised controlled
      trial. SETTING: 10 general practices in London. PARTICIPANTS: 149 patients with
      moderate or severe irritable bowel syndrome resistant to the antispasmodic
      mebeverine. INTERVENTIONS: Cognitive behaviour therapy delivered by trained
      primary care nurses plus 270 mg mebeverine taken thrice daily compared with
      mebeverine treatment alone. MAIN OUTCOME MEASURES: Primary measures were
      patients' scores on the irritable bowel syndrome symptom severity scale.
      Secondary measures were scores on the work and social adjustment scale and the
      hospital anxiety and depression scale. RESULTS: Of 334 referred patients, 72 were
      randomised to mebeverine plus cognitive behaviour therapy and 77 to mebeverine
      alone. Cognitive behaviour therapy had considerable initial benefit on symptom
      severity compared with mebeverine alone, with a mean reduction in score of 68
      points (95% confidence interval 103 to 33), with the benefit persisting at three
      months and six months after therapy (mean reductions 71 points (109 to 32) and 11
      points (20 to 3)) but not later. Cognitive behaviour therapy also showed
      significant benefit on the work and social adjustment scale that was still
      present 12 months after therapy (mean reduction 2.8 points (5.2 to 0.4)), but had
      an inconsistent effect on the hospital anxiety and depression scale. CONCLUSION:
      Cognitive behaviour therapy delivered by primary care nurses offered additional
      benefit over mebeverine alone up to six months, although the effect had waned by
      12 months. Such therapy may be useful for certain patients with irritable bowel
      syndrome in primary care.

PMID- 16093253
TI  - Effectiveness of innovations in nurse led chronic disease management for patients
      with chronic obstructive pulmonary disease: systematic review of evidence.
AB  - OBJECTIVE: To determine the effectiveness of innovations in management of chronic
      disease involving nurses for patients with chronic obstructive pulmonary disease
      (COPD). DESIGN: Systematic review of randomised controlled trials. DATA SOURCES:
      24 electronic databases searched for English or Dutch language studies published
      between January 1980 and January 2005. REVIEW METHODS: Included studies described
      inpatient, outpatient, and community based interventions for chronic disease
      management that were led, coordinated, or delivered by nurses. Hospital at home
      and early discharge schemes for acute exacerbations of COPD were excluded.
      RESULTS: We identified nine relevant randomised controlled trials, most of which
      had some potential methodological flaws. All the interventions seemed to be
      variations on a case management model. The interventions described could be
      divided into brief (one month) and longer term (around a year) or more intensive
      interventions. Only two studies examined the effect of brief interventions, these
      found little evidence of any benefit. Meta-analysis of the long term
      interventions failed to detect any influence on mortality at 9-12 months' follow
      up (Peto odds ratio 0.85, 95% confidence interval 0.58 to 1.26). There was
      evidence that the long term interventions had not improved patients' health
      related quality of life, psychological wellbeing, disability, or pulmonary
      function. The evidence on whether long term interventions reduced readmissions to
      hospital was equivocal, but the only study exclusively directed at patients on
      long term oxygen therapy reported a reduction in readmission. We identified
      several outcomes where little or no evidence was available; these included
      patients' satisfaction, self management skills, adherence with treatment
      recommendations, the likelihood of smoking cessation, and the effect of the
      interventions on carers. CONCLUSION: There is little evidence to date to support
      the widespread implementation of nurse led management interventions for COPD, but
      the data are too sparse to exclude any clinically relevant benefit or harm
      arising from such interventions.

PMID- 16093254
TI  - Appropriateness of use of medicines in elderly inpatients: qualitative study.
AB  - OBJECTIVES: To explore the processes leading to inappropriate use of medicines
      for elderly patients admitted for acute care. DESIGN: Qualitative study with
      semistructured interviews with doctors, nurses, and pharmacists; focus groups
      with inpatients; and observation on the ward by clinical pharmacists for one
      month. SETTING: Five acute wards for care of the elderly in Belgium.
      PARTICIPANTS: 5 doctors, 4 nurses, and 3 pharmacists from five acute wards for
      the interviews; all professionals and patients on two acute wards for the
      observation and 17 patients (from the same two wards) for the focus groups.
      RESULTS: Several factors contributed to inappropriate prescribing, counselling,
      and transfer of information on medicines to primary care. Firstly, review of
      treatment was driven by acute considerations, the transfer of information on
      medicines from primary to secondary care was limited, and prescribing was often
      not tailored to elderly patients. Secondly, some doctors had a passive attitude
      towards learning: they thought it would take too long to find the information
      they needed about medicines and lacked self directed learning. Finally, a
      paternalistic doctor-patient relationship and difficulties in sharing decisions
      about treatment between prescribers led to inappropriate use of medicines.
      Several factors, such as the input of geriatricians and good communication
      between members of the multidisciplinary geriatric team, led to better use of
      medicines. CONCLUSIONS: In this setting, improvements targeted at the abilities
      of individuals, better doctor-patient and doctor-doctor relationships, and
      systems for transferring information between care settings will increase the
      appropriate use of medicines in elderly people.

PMID- 16093255
TI  - Ten year follow-up of a randomised controlled trial of care in a stroke
      rehabilitation unit.

PMID- 16093256
TI  - Effects of activator and activator headgear treatment: comparison with untreated
      Class II subjects.
AB  - The aims of this study were to determine whether the activator and activator
      headgear encourage mandibular growth, and whether there is any superiority of one
      appliance over the other or if the resultant changes are due to normal growth.
      Forty-nine skeletal Class II division 1 patients were selected. Thirty-three (13
      females, 20 males; mean age 12.52 +/- 1.42 years) were treated with an Andresen
      activator and the remaining 16 (7 females, 9 males; mean age 13.04 +/- 1.47
      years) with an activator headgear combination. Twenty Class II subjects (9
      females, 11 males; mean age 12.57 +/- 1.11 years) who had previously refused
      treatment served as a control group. Cephalometric landmarks were marked and
      digitized by one author to avoid inter-observer variability. Nine angular and 12
      linear measurements were established and measured using Vistadent AT software. A
      paired-sample t-test and an ANOVA test were used to statistically evaluate the
      findings. The results revealed that both the activator and the activator headgear
      combination significantly (P < 0.001) encouraged mandibular growth, but had
      little restraining effect on the maxilla. The mandibular incisors were more
      controlled in the activator headgear combination group. The resultant skeletal,
      dentoalveolar and soft tissue changes differed significantly from those due to
      growth.

PMID- 16093257
TI  - Age-related changes in sagittal relationship between the maxilla and mandible.
AB  - The aim of the study was to assess age-related changes in sagittal jaw
      relationship during pre-pubertal and pubertal development on the basis of angular
      [ANB, anteroposterior dysplasia indicator (APDI) and A-B plane angle] and linear
      (Wits, AF-BF, App-Bpp, and App-Pgpp) measurements. Lateral cephalograms of
      orthodontically untreated subjects were evaluated at 7, 9, 11, 13 and 15 years of
      age. Cephalometric standards and age-related changes were determined on the basis
      of Class I subjects with a good occlusion (n = 18, 10 males and 8 females). With
      respect to changes related to growth, the main findings were, in both genders, a
      statistically significant age-related decrease in ANB angle, App-Bpp and App
      Pgpp, a significant increase in APDI, but no age-related change in Wits. A
      reduction of sagittal jaw distance during pre-pubertal and pubertal development
      was observed arising from a relative dominance of sagittal mandibular growth. For
      an evaluation of differences concerning jaw relationship in Class II subjects, a
      group with Class II division 1 malocclusions (n = 17) and a group with Class II
      division 2 malocclusions (n = 12 were compared with two control groups, i.e. the
      good occlusion group and a Class I group (n = 37). Conclusions about the sagittal
      discrepancy in Class II division 1 and Class II division 2 subjects depended on
      the geometric reference used in the various parameters, and further research is
      called for with respect to the diagnostic performance of the various
      measurements. Differences between Class II subjects and controls present at 15
      years of age were already established at 7 years of age, but were less
      pronounced.

PMID- 16093258
TI  - Effect of cervical headgear wear on dynamic measurement of head position.
AB  - The aim of this study was to identify the effect of cervical headgear (CHG) wear
      on dynamic measurement of head posture during walking. Six male and 10 female
      patients (mean age, 11.9 +/- 1.9 years) who were receiving CHG therapy for
      correction of a Class II molar relationship as part of their orthodontic
      treatment were included in this study. Dynamic head posture measurements were
      recorded using an inclinometer and data logger apparatus during a walking session
      of 5 minutes. This procedure was repeated before (T1) and after (T2) insertion of
      CHG. The T1 and T2 measurements were repeated twice at 30-minute intervals. The
      mean dynamic head posture was calculated for each subject using the collected
      data. The means of these measurements were statistically compared using a paired
      t-test. Of the 16 subjects, 14 showed a cranial flexion with CHG wear in relation
      to T1 (1.4 to 8.9 degrees). The other two subjects showed a cranial extension of 
      1.6 and -3.8 degrees. The mean values at T1, T2 and T1-T2 were 1.4, -1.8, and 3.1
      degrees, respectively, which indicated a mean cranial flexion at T2 in relation
      to T1. According to the paired sample t-test, there were statistically
      significant differences between the two measurements of dynamic head posture
      recorded before and after CHG insertion (P < 0.001). CHG wear causes a
      significant cranial flexion which may be responsible for its effects on the
      mandible.

PMID- 16093259
TI  - Ion release and cytotoxicity of stainless steel wires.
AB  - Heat treatment is generally applied to orthodontic stainless steel (SS) wires to
      relieve the stresses that result from their manipulation by orthodontists. The
      quality and thickness of the oxide films formed on the surface of heat-treated
      wires can vary, and it is believed that these oxide films can influence the
      properties of heat-treated wires. The aim of this study was to investigate the
      influence of heat treatment and cooling methods on the amount of metal ions
      released and to examine the cytotoxicity of heat-treated wires. In this study,
      four types of SS wires (Remanium, Permachrome, Colboloy and Orthos) with a cross
      sectional area of 0.41 x 0.56 mm were investigated. These wires were heat-treated
      in a vacuum, air, or argon environment, and were cooled in either a furnace or a
      water bath. Four control groups and 24 experimental groups were classified
      according to the type of wires, heat treatment conditions and cooling methods. In
      each group, the amount of nickel released as well as its cytotoxicity was
      investigated. The concentration of dissolved nickel ions in artificial saliva was
      measured for a period of up to 12 weeks. In all groups, the concentration of
      dissolved nickel ions in artificial saliva was lowest for the vacuum heat
      treatment-furnace cooling group and a significant difference was shown compared
      with the other experimental groups. The concentration of dissolved nickel ions in
      artificial saliva was highest in the groups heat-treated in air (P < 0.05), while
      the amount of nickel released was highest in the Remanium and Colboloy (P <
      0.05). The cytotoxicity was mild in all the experimental groups but the response
      index of the air groups was slightly higher than in the other groups. According
      to these results, SS wires retain their high corrosion resistance and low ion
      release rate when heat-treated in a vacuum and cooled in a furnace.

PMID- 16093260
TI  - Maxillary canine anomalies and tooth agenesis.
AB  - The aims of the study were to analyse the records of 26 subjects (18 females,
      eight males) with maxillary canine-first premolar transposition (Mx.C.P1)
      together with 160 subjects with a palatally displaced canine (PDC) to determine
      the pattern of tooth agenesis in these cases and to compare them with similar
      samples reported in the literature. A strong association between Mx.C.P1, lateral
      incisor and lower second premolar agenesis was found, with a 20 per cent
      prevalence of lateral incisor agenesis and a 24 per cent prevalence of lower
      second premolar agenesis. There was a lesser association with third molar (M.3)
      agenesis, with a prevalence of 52.2 per cent. Weaker associations were found for
      a PDC, with a prevalence of 5 per cent for lateral incisor agenesis. The
      prevalence of lower second premolar (5 per cent) and M.3 (27.5 per cent) agenesis
      approached reference values. Evidence for the implication of the MSX1 or PAX9
      genes in the aetiology of PDC was weak.

PMID- 16093261
TI  - Modified natural cycle IVF for poor responders.

PMID- 16093262
TI  - The epigenetic environment: secondary sex ratio depends on differential survival
      in embryogenesis: comment 1.

PMID- 16093263
TI  - The epigenetic environment: secondary sex ratio depends on differential survival
      in embryogenesis: comment 2.

PMID- 16093264
TI  - Is the dose to inhibit the COX-2 enzyme in nude mice also adequate in 'human'
      endometrial tissues?

PMID- 16093265
TI  - Peripartum cardiomyopathy (PPCM) in both surrogate and biological mother.

PMID- 16093266
TI  - Exercise training: only if needed?

PMID- 16093267
TI  - Testosterone therapy in men with moderate severity heart failure: a double-blind
      randomized placebo controlled trial.
AB  - AIMS: Chronic heart failure is associated with maladaptive and prolonged
      neurohormonal and pro-inflammatory cytokine activation causing a metabolic shift
      favouring catabolism, vasodilator incapacity, and loss of skeletal muscle bulk
      and function. In men, androgens are important determinants of anabolic function
      and physical strength and also possess anti-inflammatory and vasodilatory
      properties. METHODS AND RESULTS: We conducted a randomized, double-blind, placebo
      controlled parallel trial of testosterone replacement therapy (5 mg Androderm) at
      physiological doses in 76 men (mean+/-SD, age 64+/-9.9) with heart failure
      (ejection fraction 32.5+/-11%) over a maximum follow-up period of 12 months. The
      primary endpoint was functional capacity as assessed by the incremental shuttle
      walk test (ISWT). At baseline, 18 (24%) had serum testosterone below the normal
      range and bioavailable testosterone correlated with distance walked on the
      initial ISWT (r=0.3, P=0.01). Exercise capacity significantly improved with
      testosterone therapy compared with placebo over the full study period (mean
      change +25+/-15 m) corresponding to a 15+/-11% improvement from baseline (P=0.006
      ANOVA). Symptoms improved by at least one functional class on testosterone in 13
      (35%) vs. 3 (8%) on placebo (P=0.01). No significant changes were found in
      handgrip strength, skeletal muscle bulk by cross-sectional computed tomography,
      or in tumour necrosis factor levels. Testosterone therapy was safe with no excess
      of adverse events although the patch preparation was not well tolerated by the
      study patients. CONCLUSION: Testosterone replacement therapy improves functional
      capacity and symptoms in men with moderately severe heart failure.

PMID- 16093268
TI  - Plant ecology of Australia's tropical floodplain wetlands: a review.
AB  - AIMS: Despite the biodiversity values of the freshwater floodplains of northern
      Australia being widely recognized, there has not been a concomitant investment in
      developing the extent of knowledge of the basic functions and ecological
      processes that underpin the ecological character of these habitats. This review
      addresses the extent of our knowledge on the plant ecology of these wetlands and
      covers: the relationships between the climate and the hydrological regime on the
      floodplain; the vegetation patterns, succession and adaptation; and primary
      production. SCOPE: Information is available on the seasonal, but less regularly
      on the inter-annual, dynamics of the macrophytic vegetation and its evident inter
      relationship with the extent, depth and duration of inundation by seasonal
      flooding. The available scientifically collected information on plant
      distribution and relationship with the water regime could be complemented by more
      attention to traditional knowledge. The productivity of the vegetation is high
      the dominant wetland grass species have an annual dry weight production of 0.5
      2.1 kg m-2 and the surrounding riparian (Melaleuca) trees contribute litterfall
      of 0.7-1.5 kg (dry weight) m-2 year-1, approximately 70% due to leaf-fall. The
      availability of dissolved oxygen in the water is known to vary diurnally and
      seasonally, at least in some habitats. The importance of seasonal differences in
      the availability of dissolved oxygen for the growth of micro- and macrophytic
      vegetation has not been investigated. The seasonal distribution and growth of
      plant species on a few floodplains have been investigated, and maps at scales of
      1:10,000 to 1:100,000 are available for these. However, only on a few occasions
      have longer term analyses been conducted and long-term changes in the vegetation
      measured and assessed. Species lists and categorization of growth strategies and
      forms are available and provide a basis for further ecological investigation.
      CONCLUSIONS: Despite the large investment in managing the many pressures that
      have degraded the ecological character of these highly valued wetlands, the
      fundamental ecological processes that underpin the biodiversity values have not
      received the same level of attention. Further information on plant growth and the
      environmental factors that drive seasonal and annual changes in vegetation
      distribution and productivity is required to assist managers in attending to
      changes due to increasing invasive species and changes in fire regimes.

PMID- 16093269
TI  - Plant traits, environmental factors, and pollinator visitation in winter
      flowering Helleborus foetidus (Ranunculaceae).
AB  - BACKGROUND AND AIMS: This study examined the effect of plant traits and
      environmental factors on pollinator visitation in the winter-flowering Helleborus
      foetidus (Ranunculaceae) in three distant regions in the Iberian Peninsula.
      METHODS: Geographical variation in floral visitor assemblage, plant traits and
      environmental factors were analysed during the flowering season. KEY RESULTS:
      Differences were found in all plant traits measured (number of open flowers,
      flower size, number of stamens per flower, and number of nectaries) both within
      and among regions, and differences among regions in all the environmental factors
      considered (air temperature, exposure to sunlight, canopy cover, and distance to
      the nearest neighbour). Differences were also found among regions in the
      probability that plants would be visited by pollinators. CONCLUSIONS: The results
      show that, although floral display (i.e. number of open flowers on a plant on a
      given day) consistently explained among-plant differences in visitation rate in
      all regions, visitation rate was not significantly affected by any other
      biological or environmental variable. In Helleborus foetidus, then, 'how' the
      plant is would seem to be more important than 'where' is it.

PMID- 16093270
TI  - Kinetics of ethanol and acetaldehyde release suggest a role for acetaldehyde
      production in tolerance of rice seedlings to micro-aerobic conditions.
AB  - BACKGROUND AND AIMS: This paper examines the basis of the greater tolerance of an
      indica rice cultivar FR13A to complete submergence compared with relatively
      intolerant japonica rice CT6241. We study whether this superior tolerance is
      related to its greater tolerance to O2 shortage and to an ability to run a more
      favourable rate of alcoholic fermentation during and after O2 deprivation.
      METHODS Fermentation products were analysed using sensitive laser-based
      photoacoustics at high time resolution to establish patterns and rates of ethanol
      and acetaldehyde emission by intact rice seedlings exposed to micro-aerobic (0.05
      0.5 % O2) or zero O2 supply, and also during their return to air. Oxygen and CO2
      emission or uptake was also quantified. KEY RESULTS: In the dark, no acetaldehyde
      and ethanol emission was observed until external O2 concentration in a gas phase
      decreased to <or=0.3% O2. The ethanol production rate was maximal in 0% O2,
      similar in both cultivars and gradually diminished with increasing O2
      concentration. Lag time for induction of fermentation increased with O2 up to
      0.3% and was shorter in CT6241. Light strongly suppressed fermentation. In
      contrast to that of ethanol, emission of acetaldehyde in the dark under micro
      aerobic conditions (<or=0.15% O2 gas phase) exceeded that under anaerobiosis, was
      maximal in 0.05% O2 and was greater in FR13A than in CT6241. A drop in
      acetaldehyde emission to about half its value immediately followed a switch to
      anaerobic conditions after 6.5 h treatment under 0.05% O2, while ethanol release
      showed a further increase. A large peak in acetaldehyde emission immediately
      followed the return of seedlings to air after treatment with <or=0.15% O2. The
      emission from FR13A was up to three times larger than from CT6241. CONCLUSIONS:
      Tolerance to submergence in FR13A appears not to be connected to its rate of
      ethanol production during anaerobiosis, but to the increased acetaldehyde output
      during and after experiencing micro-aerobic conditions (0.05-0.15% O2). Extra
      acetaldehyde production from ethanol may be a consequence of diversion of the
      reactive oxygen species away from the damaging lipid peroxidation pathway.

PMID- 16093271
TI  - Rice: sulfide-induced barriers to root radial oxygen loss, Fe2+ and water uptake,
      and lateral root emergence.
AB  - BACKGROUND AND AIMS: Akagare and Akiochi are diseases of rice associated with
      sulfide toxicity. This study investigates the possibility that rice reacts to
      sulfide by producing impermeable barriers in roots. METHODS: Root systems of
      rice, Oryza sativa cv. Norin 36, were subjected to short-term exposure to 0.174
      mm sulfide (5.6 ppm) in stagnant solution. Root growth was monitored; root
      permeability was investigated in terms of polarographic determinations of oxygen
      efflux from fine laterals and the apices of adventitious roots, water uptake,
      anatomy and permeability to Fe2+ using potassium ferricyanide. KEY RESULTS: Both
      types of root responded rapidly to the sulfide with immediate cessation of
      growth, decreased radial oxygen loss (ROL) to the rhizospheres and reduced water
      uptake. Profiles of ROL measured from apex to basal regions of adventitious roots
      indicated that more intense barriers to ROL than normal were formed around the
      apices. Absorption of Fe2+ appeared to be impeded in sulfide-treated roots. In
      adventitious roots, deposition of lipid material (suberisation) and thickenings
      of walls within the superficial cell layers were obvious within a week after
      lifting the treatment and could prevent the emergence of laterals and commonly
      result in their upward longitudinal growth within the cortex. Death of laterals
      sometimes occurred prior to emergence; emergent laterals eventually died. In
      adventitious roots, blockages formed within the vascular and aeration systems in
      response to the sulfide. CONCLUSIONS: In both adventitious and lateral roots,
      sulfide-induced cell wall suberization and thickening of the superficial layers
      were correlated with reduced permeability to O2, water and Fe2+. This study sheds
      light on some of the symptoms of diseases such as Akiochi. The results correlate
      with the authors' previous findings on the effects on roots of sulfide and lower
      organic acids in Phragmites and of acetic acid in rice.

PMID- 16093272
TI  - Stem photosynthesis not pressurized ventilation is responsible for light-enhanced
      oxygen supply to submerged roots of alder (Alnus glutinosa).
AB  - BACKGROUND AND AIMS: Claims that submerged roots of alder and other wetland trees
      are aerated by pressurized gas flow generated in the stem by a light-induced
      thermo-osmosis have seemed inconsistent with root anatomy. Our aim was to seek a
      verification using physical root-stem models, stem segments with or without
      artificial roots, and rooted saplings. METHODS: Radial O2 loss (ROL) from roots
      was monitored polarographically as the gas space system of the models, and stems
      were pressurized artificially. ROL and internal pressurization were also measured
      when stems were irradiated and the xylem stream was either CO2 enriched or not.
      Stem photosynthesis and respiration were measured polarographically. Stem and
      root anatomy were examined by light and fluorescence microscopy. KEY RESULTS:
      Pressurizing the models and stems to <or=10 kPa, values much higher than those
      reportedly generated by thermo-osmosis, created only a negligible density-induced
      increase in ROL, but ROL increased rapidly when ambient O2 concentrations were
      raised. Internal pressures rose by several kPa when shoots were exposed to high
      light flux and ROL increased substantially, but both were due to O2 accumulation
      from stem photosynthesis using internally sourced CO2. Increased stem pressures
      had little effect on O2 transport, which remained largely diffusive. Oxygen flux
      from stems in high light periods indicated a net C gain by stem photosynthesis.
      Chloroplasts were abundant in the secondary cortex and secondary phloem, and
      occurred throughout the secondary xylem rays and medulla of 3-year-old stems.
      Diurnal patterns of ROL, most marked when light reached submerged portions of the
      stem, were modified by minor variations in light flux and water level. Low root
      temperatures also helped improve root aeration. CONCLUSIONS: Pressurized gas flow
      to submerged roots does not occur to any significant degree in alder, but stem
      photosynthesis, using internally sourced CO2 from respiration and the
      transpiration stream, may play an important role in root aeration in young trees
      and measurably affect the overall carbon balance of this and other species.

PMID- 16093273
TI  - Enantiomer/enantiomer interactions between the S- and R- isomers of omeprazole in
      human cytochrome P450 enzymes: major role of CYP2C19 and CYP3A4.
AB  - We investigated the enzyme kinetic basis for the stereoselective disposition of R
      and S-omeprazole (OME) and racemic OME in human liver microsomes. OME is
      primarily metabolized by the hepatic cytochrome P450 enzyme system (CYP2C19 and
      3A4). The metabolism of each enantiomer and pseudoracemic OME was studied using
      unlabeled and (13)C(7)-labeled enantiomers. The enantiomers inhibited each
      other's metabolism competitively in human liver microsomes and in recombinant
      CYP2C19 and 3A4. The results obtained with the individual enantiomers allowed
      successful prediction of the enzyme kinetics for the pseudoracemate. The
      intrinsic clearance of each enantiomer in a pseudoracemic mixture remained the
      same as those of the individually incubated enantiomers, although K(m) and V(max)
      decreased. In the pseudoracemate, the relative contribution of CYP2C19 and 3A4 to
      5-hydroxylation and 5'-O-demethylation of R-OME was comparable to that obtained
      for the incubation of R-OME alone. For S-OME, however, the presence of its
      antipode greatly increased the contribution of CYP3A4, with increasing
      concentrations, compared with that obtained when incubating S-OME alone. The
      results of our in vitro study clearly show metabolic interactions between the OME
      enantiomers, which may also occur in vivo. Because the enantiomers of OME produce
      similar pharmacological effects, the enantiomer interactions should not
      significantly affect the pharmacodynamics. On the other hand, the use of the S
      enantiomer results in less complex enzyme kinetics than those of the racemate;
      thus, the outcome of its clinical use is more predictable.

PMID- 16093274
TI  - DAF-FM (4-amino-5-methylamino-2',7'-difluorofluorescein) diacetate detects
      impairment of agonist-stimulated nitric oxide synthesis by elevated glucose in
      human vascular endothelial cells: reversal by vitamin C and L-sepiapterin.
AB  - Elevated plasma glucose, as commonly seen in types I and II diabetes mellitus, is
      known to result in endothelial dysfunction, a condition characterized by a loss
      of nitric oxide (NO)-dependent regulation of vascular tone. In the present study,
      we have utilized a recently developed NO-sensitive fluorescent dye, DAF-FM (4
      amino-5-methylamino-2',7'-difluorofluorescein) diacetate to directly examine the
      consequences of elevated glucose on agonist-evoked NO synthesis in cultured human
      vascular endothelial cells. Exposure of cells for 5 to 7 days to high (20 mM)
      external glucose markedly reduced NO production in response to ATP, histamine, or
      the calcium ionophore calcimycin A23187 compared with 5 and 10 mM glucose
      concentrations. However, high glucose did not affect agonist-evoked elevations in
      cytosolic-free calcium, as monitored by Fluo-3. The addition of vitamin C (150
      microM) and L-sepiapterin (20 microM) for approximately 24 h to 20 mM glucose
      treated cells improved stimulus-evoked NO synthesis but had no effect on cells
      exposed to either 5 or 10 mM glucose. Likewise, impaired NO production in high
      glucose-treated cells was largely reversed by exposure ( approximately 3 h) to
      superoxide dismutase. Cellular levels of endothelial nitric-oxide synthase
      protein were unaltered by elevated glucose treatment, and no further change was
      observed after the addition of vitamin C and l-sepiapterin. Taken together, the
      results of our study serve to directly explain at the cellular level how glucose
      impaired NO production in human endothelial cells may be reversed by agents that
      are reported clinically to improve endothelium-dependent vasorelaxation in
      patients.

PMID- 16093275
TI  - Comprehensive geriatric assessment predicts tolerance to chemotherapy and
      survival in elderly patients with advanced ovarian carcinoma: a GINECO study.
AB  - BACKGROUND: Data from prospective clinical trials are needed to better define
      standards of care in elderly patients with advanced ovarian carcinoma and to
      demonstrate the interest of Comprehensive Geriatric Assessment (CGA) in this
      fragile and heterogeneous population. PATIENTS AND METHODS: From July 1998 to
      October 2000, 83 advanced ovarian carcinoma patients >70 years old received
      carboplatin AUC 5 and cyclophosphamide 600 mg/m2, on day 1 of six 28-day cycles.
      The clinical and biological geriatric covariates prospectively studied were:
      comorbidities, comedications, cognitive functions (Mini-Mental test), nutritional
      status and autonomy. RESULTS: Patient characteristics were: median age 76 years,
      serous histology (73%), FIGO stage III (75%), optimal initial surgery (21%) and
      performance status (PS) > or =2 (44%). Sixty patients (72%) received six
      chemotherapy cycles without severe toxicity (STox) or tumor progression.
      Multivariate analysis retained three factors as independent predictors of STox:
      symptoms of depression at baseline (P = 0.006), dependence (P = 0.048) and PS >
      or =2 (P = 0.026). Independent prognostic factors identified for overall survival
      (Cox model) were depression (P = 0.003), FIGO stage IV (P = 0.007) and more than
      six different comedications per day (P = 0.043). CONCLUSION: CGA could predict
      STox and overall survival of elderly advanced ovarian carcinoma patients.

PMID- 16093276
TI  - Extended field radiotherapy, combined modality treatment or involved field
      radiotherapy for patients with stage IA lymphocyte-predominant Hodgkin's
      lymphoma: a retrospective analysis from the German Hodgkin Study Group (GHSG).
AB  - BACKGROUND: Since there are no randomized studies, the treatment of choice for
      patients with early stage lymphocyte-predominant Hodgkin's lymphoma (LPHL)
      remains unclear. We thus reviewed all LPHL cases registered in the database of
      the German Hodgkin Study Group (GHSG) and compared the different treatment
      approaches, such as extended field (EF), involved field (IF) radiation and
      combined modality (CM) treatment for LPHL stage IA patients. PATIENTS AND
      METHODS: One hundred and thirty-one patients with LPHL in clinical stage IA
      without risk factors were analyzed. Forty-five patients were treated with EF
      radiotherapy, 45 patients with IF radiation and 41 patients received CM
      treatment. The median follow-up was 78 months in the EF group, 40 months after CM
      and 17 months after IF, respectively. RESULTS: A total of 129 patients achieved
      complete remission (CR and CRu): 98% after EF radiotherapy, 100% after IF
      radiation and 95% after CM. With a median follow-up of 43 months there were 5%
      relapses and only three patients died. Toxicity of treatment was generally mild
      with most events observed after CM. CONCLUSION: In terms of remission induction
      IF radiotherapy for stage IA LPHL patients is as effective as EF or CM treatment.
      However, longer follow-up is needed before final conclusion as the optimal
      therapy.

PMID- 16093277
TI  - Na+-dependent HCO3- uptake into the rat choroid plexus epithelium is partially
      DIDS sensitive.
AB  - Several studies suggest the involvement of Na+ and HCO3- transport in the
      formation of cerebrospinal fluid. Two Na+-dependent HCO3- transporters were
      recently localized to the epithelial cells of the rat choroid plexus (NBCn1 and
      NCBE), and the mRNA for a third protein was also detected (NBCe2) (Praetorius J,
      Nejsum LN, and Nielsen S. Am J Physiol Cell Physiol 286: C601-C610, 2004). Our
      goal was to immunolocalize the NBCe2 to the choroid plexus by
      immunohistochemistry and immunogold electronmicroscopy and to functionally
      characterize the bicarbonate transport in the isolated rat choroid plexus by
      measurements of intracellular pH (pHi) using a dual-excitation wavelength pH
      sensitive dye (BCECF). Both antisera derived from COOH-terminal and NH2-terminal
      NBCe2 peptides localized NBCe2 to the brush-border membrane domain of choroid
      plexus epithelial cells. Steady-state pHi in choroidal cells increased from 7.03
      +/- 0.02 to 7.38 +/- 0.02 (n=41) after addition of CO2/HCO3- into the bath
      solution. This increase was Na+ dependent and inhibited by the Cl- and HCO3-
      transport inhibitor DIDS (200 muM). This suggests the presence of Na+-dependent,
      partially DIDS-sensitive HCO3- uptake. The pHi recovery after acid loading
      revealed an initial Na+ and HCO3- -dependent net base flux of 0.828 +/- 0.116
      mM/s (n = 8). The initial flux in the presence of CO2/HCO3- was unaffected by
      DIDS. Our data support the existence of both DIDS-sensitive and -insensitive Na+-
      and HCO3- -dependent base loader uptake into the rat choroid plexus epithelial
      cells. This is consistent with the localization of the three base transporters
      NBCn1, Na+-driven Cl- bicarbonate exchanger, and NBCe2 in this tissue.

PMID- 16093278
TI  - Calcium phosphate precipitation in the sarcoplasmic reticulum reduces action
      potential-mediated Ca2+ release in mammalian skeletal muscle.
AB  - During vigorous exercise, Pi concentration levels within the cytoplasm of fast
      twitch muscle fibers may reach > or =30 mM. Cytoplasmic Pi may enter the
      sarcoplasmic reticulum (SR) and bind to Ca2+ to form a precipitate (CaPi), thus
      reducing the amount of releasable Ca2+. Using mechanically skinned rat fast
      twitch muscle fibers, which retain the normal action potential-mediated Ca2+
      release mechanism, we investigated the consequences of Pi exposure on normal
      excitation-contraction coupling. The total amount of Ca2+ released from the SR by
      a combined caffeine/low-Mg2+ concentration stimulus was reduced by approximately
      20%, and the initial rate of force development slowed after 2-min exposure to 30
      mM Pi (with or without the presence creatine phosphate). Peak (50 Hz) tetanic
      force was also reduced (by approximately 25% and approximately 45% after 10 and
      30 mM Pi exposure, respectively). Tetanic force responses produced after 30 mM Pi
      exposure were nearly identical to those observed in the same fiber after
      depletion of total SR Ca2+ by approximately 35%. Ca2+ content assays revealed
      that the total amount of Ca2+ in the SR was not detectably changed by exposure to
      30 mM Pi, indicating that Ca2+ had not leaked from the SR but instead formed a
      precipitate with the Pi, reducing the amount of available Ca2+ for rapid release.
      These results suggest that CaPi precipitation that occurs within the SR could
      contribute to the failure of Ca2+ release observed in the later stages of
      metabolic muscle fatigue. They also demonstrate that the total amount of Ca2+
      stored in the SR cannot drop substantially below the normal endogenous level
      without reducing tetanic force responses.

PMID- 16093279
TI  - Modulation of intracellular Ca2+ release and capacitative Ca2+ entry by CaMKII
      inhibitors in bovine vascular endothelial cells.
AB  - The effects of inhibitors of CaMKII on intracellular Ca2+ signaling were examined
      in single calf pulmonary artery endothelial (CPAE) cells using indo-1
      microfluorometry to measure cytoplasmic Ca2+ concentration ([Ca2+]i). The three
      CaMKII inhibitors, KN-93, KN-62, and autocamtide-2-related inhibitory peptide
      (AIP), all reduced the plateau phase of the [Ca2+]i transient evoked by
      stimulation with extracellular ATP. Exposure to KN-93 or AIP alone in the
      presence of 2 mM extracellular Ca2+ resulted in a dose-dependent increase of
      [Ca2+]i consisting of a rapid and transient Ca2+ spike followed by a small
      sustained plateau phase of elevated [Ca2+]i. Exposure to KN-93 in the absence of
      extracellular Ca2+ caused a transient rise of [Ca2+]i, suggesting that exposure
      to CaMKII inhibitors directly triggered release of Ca2+ from intracellular
      endoplasmic reticulum (ER) Ca2+ stores. Repetitive stimulation with KN-93 and
      ATP, respectively, revealed that both components released Ca2+ largely from the
      same store. Pretreatment of CPAE cells with the membrane-permeable inositol 1,4,5
      trisphosphate (IP3) receptor blocker 2-aminoethoxydiphenyl borate caused a
      significant inhibition of the KN-93-induced Ca2+ response, suggesting that
      exposure to KN-93 affects Ca2+ release from an IP3-sensitive store. Depletion of
      Ca2+ stores by exposure to ATP or to the ER Ca2+ pump inhibitor thapsigargin
      triggered robust capacitative Ca2+ entry (CCE) signals in CPAE cells that could
      be blocked effectively with KN-93. The data suggest that in CPAE cells, CaMKII
      modulates Ca2+ handling at different levels. The use of CaMKII inhibitors
      revealed that in CPAE cells, the most profound effects of CaMKII are inhibition
      of release of Ca2+ from intracellular stores and activation of CCE.

PMID- 16093280
TI  - N-methyl-D-glucamine and propidium dyes utilize different permeation pathways at
      rat P2X(7) receptors.
AB  - Activation of membrane P2X(7) receptors by extracellular ATP [or its analog 2',3'
      O-(4-benzoylbenzoyl)-ATP] results in the opening within several milliseconds of
      an integral ion channel that is permeable to small cations. If the ATP
      application is maintained for several seconds, two further sequelae occur: there
      is a gradual increase in permeability to the larger cation N-methyl-d-glucamine
      and the cationic propidium dye quinolinium, 4-[(3-methyl-2(3H)
      benzoxazolylidene)methyl]-1-[3-(triethylammonio)propyl]diiodide (YO-PRO-1) enters
      the cell. The similarity in the time course of these two events has led to the
      widespread view that N-methyl-d-glucamine and YO-PRO-1 enter through a common
      permeation pathway, the "dilating" P2X(7) receptor pore. Here we provide two
      independent lines of evidence against this view. We studied single human
      embryonic kidney cells expressing rat P2X(7) receptors with patch-clamp
      recordings of membrane current and with fluorescence measurements of YO-PRO-1
      uptake. First, we found that maintained application of the ATP analog did not
      cause any increase in N-methyl-d-glucamine permeability when the extracellular
      solution contained its normal sodium concentration, although YO-PRO-1 uptake was
      readily observed. Second, we deleted a cysteine-rich 18-amino acid segment in the
      intracellular juxtamembrane region of the P2X(7) receptor. This mutated receptor
      showed normal YO-PRO-1 uptake but had no permeability to N-methyl-d-glucamine.
      Together, the clear differential effects of extracellular sodium ions or of
      mutation of the receptor strongly suggest that N-methyl-d-glucamine and YO-PRO-1
      do not enter the cell by the same permeation pathway.

PMID- 16093281
TI  - Quantification of gap junction selectivity.
AB  - Gap junctions, which are essential for functional coordination and homeostasis
      within tissues, permit the direct intercellular exchange of small molecules. The
      abundance and diversity of this exchange depends on the number and selectivity of
      the comprising channels and on the transjunctional gradient for and chemical
      character of the permeant molecules. Limited knowledge of functionally
      significant permeants and poor detectability of those few that are known have
      made it difficult to define channel selectivity. Presented herein is a
      multifaceted approach to the quantification of gap junction selectivity that
      includes determination of the rate constant for intercellular diffusion of a
      fluorescent probe (k2-DYE) and junctional conductance (gj) for each junction
      studied, such that the selective permeability (k2-DYE/gj) for dyes with differing
      chemical characteristics or junctions with differing connexin (Cx) compositions
      (or treatment conditions) can be compared. In addition, selective permeability
      can be correlated using single-channel conductance when this parameter is also
      measured. Our measurement strategy is capable of detecting 1) rate constants and
      selective permeabilities that differ across three orders of magnitude and 2)
      acute changes in that rate constant. Using this strategy, we have shown that 1)
      the selective permeability of Cx43 junctions to a small cationic dye varied
      across two orders of magnitude, consistent with the hypothesis that the various
      channel configurations adopted by Cx43 display different selective
      permeabilities; and 2) the selective permeability of Cx37 vs. Cx43 junctions was
      consistently and significantly lower.

PMID- 16093282
TI  - Muscle LIM protein plays both structural and functional roles in skeletal muscle.
AB  - Muscle LIM protein (MLP) has been suggested to be an important mediator of
      mechanical stress in cardiac tissue, but the role that it plays in skeletal
      muscle remains unclear. Previous studies have shown that it is dramatically
      upregulated in fast-to-slow fiber-type transformation and also after eccentric
      contraction (EC)-induced muscle injury. The functional consequences of this
      upregulation, if any, are unclear. In the present study, we have examined the
      skeletal muscle phenotype of MLP-knockout (MLPKO) mice in terms of their response
      to EC-induced muscle injuries. The data suggest that while the MLPKO mice recover
      completely after EC-induced injury, their torque production lags behind that of
      heterozygous littermates in the early stages of the recovery process. This lag is
      accompanied by decreased expression of the muscle regulatory factor MyoD,
      suggesting that MLP may influence gene expression. In addition, there is evidence
      of type I fiber atrophy and a shorter resting sarcomere length in the MLPKO mice,
      but no significant differences in fiber type distribution. In summary, MLP
      appears to play a subtle role in the maintenance of normal muscle characteristics
      and in the early events of the recovery process of skeletal muscle to injury,
      serving both structural and gene-regulatory roles.

PMID- 16093283
TI  - Hypoxia and acidosis increase the secretion of catecholamines in the neonatal rat
      adrenal medulla: an in vitro study.
AB  - Hypoxia elicits catecholamine (CA) secretion from the adrenal medulla (AM) in
      perinatal animals by acting directly on chromaffin cells. However, whether
      innervation of the AM, which in the rat occurs in the second postnatal week,
      suppresses this direct hypoxic response is the subject of debate. Opioid peptides
      have been proposed as mediators of this suppression. To resolve these
      controversies, we have compared CA-secretory responses with high external
      concentrations of K+ ([K+]e) and hypoxia in the AM of neonatal (1- to 2-day-old)
      and juvenile (14- or 15- and 30-day-old) rats subjected to superfusion in vitro.
      In addition, we studied the effect of hypercapnic acidosis on the CA-secretory
      responses in the AM during postnatal development and the possible interaction
      between acidic and hypoxic stimuli. Responses to high [K+]e were comparable at
      all ages, but responses to hypoxia and hypercapnic acidosis were maximal in
      neonatal animals. Suppression of the hypoxic response in the rat AM was not
      mediated by opioids, because their agonists did not affect the hypoxic CA
      response. The association of hypercapnic acidosis and hypoxia, mimicking the
      episodes of asphyxia occurring during delivery, generates a more than additive
      secretory response in the neonatal rat AM. Our data confirm the loss of the
      direct sensitivity to hypoxia of the AM in the initial weeks of life and
      demonstrate a direct response of neonatal AM to hypercapnic acidosis. The
      synergistic effect of hypoxia and acidosis would explain the CA outburst crucial
      for adaptation to extrauterine life observed in naturally delivered mammals.

PMID- 16093284
TI  - How to improve nature: study of the electrostatic properties of the surface of
      alpha-lactalbumin.
AB  - It was recently shown that alpha-lactalbumin interacts with histones and simple
      models of histone proteins such as positively charged polyamino acids, suggesting
      that some fundamental aspects of the protein surface electrostatics may come into
      play. In the present work, the energies of charge-charge interaction in apo- and
      Ca(2+)-loaded alpha-lactalbumin were calculated using a Tanford-Kirkwood
      algorithm with either solvent accessibility correction or using a finite
      difference Poisson-Boltzmann method. The analysis revealed two major regions of
      alpha-lactalbumin that possessed highly unfavorable electrostatic potentials: (a)
      the Ca(2+)-binding loop and its neighboring residues and (b) the N-terminal
      region of the protein. Several individual mutants were prepared to neutralize
      specific individual surface acidic amino acids at both the N-terminus and Ca(2+)
      binding loop of bovine alpha-lactalbumin. These mutants were characterized by
      intrinsic fluorescence, differential scanning microcalorimetry and circular
      dichroism. The structural and thermodynamic data agree in every case with the
      theoretical predictions, confirming that the N-terminal region is very sensitive
      to changes in charge. For example, desMet D14N mutation destabilizes protein and
      decreases its calcium affinity. On the other hand, desMet E1M and desMet D37N
      substitutions increase the thermal stability and calcium affinity. The Met E1Q is
      characterized by a marked increase in protein stability, whereas desMet E7Q and
      desMet E11L display a slight increase in calcium affinity and thermal stability.
      Examination of the unfavorable energy contributed by Glu1 and the energetically
      favorable consequences of neutralizing this residue suggests that nature may have
      made an error with bovine alpha-lactalbumin from the viewpoint of stabilizing
      structure and conformation.

PMID- 16093285
TI  - Re: "Appropriate assessment of neighborhood effects on individual health:
      integrating random and fixed effects in multilevel logistic regression".

PMID- 16093286
TI  - Protective and harmful effects of neighborhood-level deprivation on individual
      level health knowledge, behavior changes, and risk of coronary heart disease.
AB  - The authors examined associations between neighborhood-level deprivation and
      cardiovascular disease-related health knowledge and behavior changes, as well as
      the estimated 12-year probability of experiencing a coronary heart disease event.
      Primary analyses included multilevel regression models among 8,197 women and men
      living in 82 neighborhoods in four northern California cities who were
      interviewed in one of five surveys conducted between 1979 and 1990. After
      controlling for age, gender, marital status, race/ethnicity, city, and time, the
      authors found that adults living in high-deprivation neighborhoods had
      significantly lower health knowledge and a higher probability of no positive
      behavior changes than did adults in moderately deprived neighborhoods (i.e.,
      harmful effects). Conversely, those living in low-deprivation neighborhoods had
      significantly higher health knowledge and lower probabilities of no positive
      behavior changes and estimated risk of coronary heart disease (i.e., protective
      effects). The association between high neighborhood deprivation and no positive
      behavior changes remained statistically significant after additional adjustment
      for a composite measure of individual-level socioeconomic status. Associations
      with neighborhood deprivation did not vary by individual-level socioeconomic
      status. These results suggest that focusing exclusively on changing individuals'
      behaviors will have a limited effect unless contextual influences at the
      neighborhood level are also addressed.

PMID- 16093287
TI  - Evaluation of offspring and maternal genetic effects on disease risk using a
      family-based approach: the "pent" design.
AB  - Diseases that develop during gestation may be influenced by the genotype of the
      mother and the inherited genotype of the embryo/fetus. However, given the
      correlation between maternal and offspring genotypes, differentiating between
      inherited and maternal genetic effects is not straightforward. The two-step
      transmission disequilibrium test was the first, family-based test proposed for
      the purpose of differentiating between maternal and offspring genetic effects.
      However, this approach, which requires data from "pents" comprising an affected
      child, mother, father, and maternal grandparents, provides biased tests for
      maternal genetic effects when the offspring genotype is associated with disease.
      An alternative approach based on transmissions from grandparents provides
      unbiased tests for maternal and offspring genetic effects but requires genotype
      information for paternal grandparents in addition to pents. The authors have
      developed two additional, pent-based approaches for the evaluation of maternal
      and offspring genetic effects. One approach requires the assumption of genetic
      mating type symmetry (pent-1), whereas the other does not (pent-2). Simulation
      studies demonstrate that both of these approaches provide valid estimation and
      testing for offspring and maternal genotypic effects. In addition, the power of
      the pent-1 approach is comparable with that of the approach based on data using
      all four grandparents.

PMID- 16093288
TI  - Use of nonsteroidal antiinflammatory drugs and risk of colon cancer in a
      population-based, case-control study of African Americans and Whites.
AB  - African Americans have the highest colon cancer incidence and mortality rates
      among all US ethnic groups. Epidemiologic studies suggest that use of
      nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a reduced risk of
      colon cancer, but no study to date with adequate sample size has reported on the
      association among African Americans. The authors examined the association between
      NSAID use and risk of colon cancer in a population-based, case-control study in
      North Carolina that enrolled 731 African-American (294 cases, 437 controls) and
      960 White (349 cases, 611 controls) participants between 1996 and 2000. Odds
      ratios were calculated using unconditional logistic regression for categories of
      NSAIDs and colon cancer risk. Inverse associations between regular NSAID use and
      colon cancer were similar for African Americans (odds ratio = 0.41, 95%
      confidence interval: 0.22, 0.77) and Whites (odds ratio = 0.48, 95% confidence
      interval: 0.28, 0.83) but stronger for women than men. Inverse associations were
      slightly weaker for occasional versus regular NSAID use, but they were similar
      for aspirin and nonaspirin NSAID use. These results add new knowledge suggesting
      that the protective effect of NSAIDs against colon cancer is similar among
      African Americans and Whites.

PMID- 16093289
TI  - A cluster analysis of bacterial vaginosis-associated microflora and pelvic
      inflammatory disease.
AB  - Controversy surrounds the association between bacterial vaginosis (BV) and pelvic
      inflammatory disease (PID). Women (N = 1,140) were ascertained at five US
      centers, enrolled (1999-2001), and followed up for a median of 3 years. Serial
      vaginal swabs were obtained for Gram's stain and cultures. PID was defined as 1)
      histologic endometritis or 2) pelvic pain and tenderness plus oral temperature
      >38.8 degrees C, leukorrhea or mucopus, erythrocyte sedimentation rate >15
      mm/hour, white blood cell count >10,000, or gonococcal/chlamydial lower genital
      infection. Exploratory factor analysis identified two discrete clusters of
      genital microorganisms. The first correlated with BV by Gram's stain and
      consisted of the absence of hydrogen peroxide-producing lactobacillus,
      Gardnerella vaginalis, Mycoplasma hominis, anaerobic gram-negative rods, and, to
      a lesser degree, Ureaplasma urealyticum. The second, unrelated to BV by Gram's
      stain, consisted of Enterococcus species and Escherichia coli. Being in the
      highest tertile in terms of growth of BV-associated microorganisms increased PID
      risk (adjusted rate ratio = 2.03, 95% confidence interval: 1.16, 3.53). Carriage
      of non-BV-associated microorganisms did not increase PID risk. Women with heavy
      growth of BV-associated microorganisms and a new sexual partner appeared to be at
      particularly high risk (adjusted rate ratio = 8.77, 95% confidence interval:
      1.11, 69.2). When identified by microbial culture, a combination of BV-related
      microorganisms significantly elevated the risk of acquiring PID.

PMID- 16093290
TI  - An approach to estimate between- and within-group correlation coefficients in
      multicenter studies: plasma carotenoids as biomarkers of intake of fruits and
      vegetables.
AB  - In a multicenter study, the overall correlation between two variables can be
      broken down into a within- and a between-group correlation reflecting
      associations at the individual and aggregate levels, respectively. A random
      effects model is used to estimate variance components of nutrition-related
      variables and the within- and between-group correlation coefficients. Using data
      from the European Prospective Investigation into Cancer and Nutrition (EPIC), the
      authors analyzed the association between levels of three plasma carotenoids
      (alpha-carotene, beta-cryptoxanthin, and lycopene) and dietary intake of three
      items (total fruits, carrots, and tomatoes), assessed through dietary
      questionnaire and single 24-hour dietary recall measurements, in a cross
      sectional study involving 3,089 subjects from nine European countries. Intraclass
      correlation coefficients were 0.178 for alpha-carotene, 0.216 for beta
      cryptoxanthin, and 0.299 for lycopene. The between-group correlation coefficients
      were higher than the within-group coefficients for all three carotenoids. For
      beta-cryptoxanthin and fruit intake, the between-group versus the within-group
      correlations were 0.78 and 0.26 for the dietary questionnaire and 0.85 and 0.19
      for the 24-hour dietary recall. Results indicate that variability of exposure is
      driven mainly by the individual compared with the aggregate variation and that
      biomarker levels perform fairly accurately in discriminating population-level
      consumption of fruits and vegetables.

PMID- 16093291
TI  - Is the risk of lung cancer reduced among eczema patients?
AB  - Persons with a history of eczema have been shown to have a reduced risk of lung
      cancer, but the evidence has been inconclusive because of the small size of
      previous studies and their limited ability to control for confounding by smoking.
      The objective of this study was to determine the role of eczema in relation to
      lung cancer while overcoming the limitations of previous investigations. Study
      subjects included 2,854 cases and 3,116 population and hospital controls
      recruited during 1998-2001 from 16 areas in the Czech Republic, Hungary, Poland,
      Romania, Russia, Slovakia, and the United Kingdom. Odds ratios were calculated
      for self-reported history of eczema via multivariate logistic regression
      modeling. The odds ratio for a history of eczema was 0.61 (95% confidence
      interval: 0.48, 0.76) after control for age, sex, study center, and cumulative
      tobacco smoking. There was no heterogeneity in the results by sex or age at onset
      of eczema. Subjects reporting use of medication for eczema had a lower odds ratio
      than subjects not reporting such use. This study provides further evidence for an
      inverse association between history of eczema and lung cancer risk, which is
      unlikely to be due to chance, bias, or confounding.

PMID- 16093292
TI  - Maternal serum levels of polychlorinated biphenyls and 1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene (DDE) and time to pregnancy.
AB  - Polychlorinated biphenyls (PCBs), once used widely in transformers and other
      applications, and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), the main
      metabolite of the pesticide 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT),
      are hormonally active agents. Changes in menstrual cycle functioning associated
      with PCBs and DDE, and increased odds of spontaneous abortion associated with
      DDE, suggest that these compounds could affect fertility. The authors
      investigated the association between PCB and DDE exposure and time to pregnancy
      by using serum levels measured in 390 pregnant women in the Collaborative
      Perinatal Project enrolled at 12 study centers in the United States from 1959 to
      1965. They estimated adjusted fecundability odds ratios by using Cox proportional
      hazards modeling for discrete time data. Compared with time to pregnancy for
      women in the lowest exposure category (PCBs < 1.24 microg/liter, DDE < 14
      microg/liter), time to pregnancy increased for women in the highest exposure
      category in terms of both PCBs (fecundability odds ratio for PCBs > or = 5.00
      microg/liter = 0.65, 95% confidence interval: 0.36, 1.18) and DDE (fecundability
      odds ratio for DDE > or = 60 microg/liter = 0.65, 95% confidence interval: 0.32,
      1.31). Overall, time to pregnancy increased with increasing serum PCB levels but
      was less suggestive of an association with DDE. Both trends were imprecise and
      attenuated when expressed on a lipid basis. Overall, evidence of an association
      between PCB or DDE exposure and time to pregnancy was weak and inconclusive.

PMID- 16093293
TI  - Gas cooking and smoking habits and the risk of childhood and adolescent wheeze.
AB  - The authors investigated the risk of wheezing illnesses in relation to
      contemporaneous pollutant exposures (gas cooking, heating, and smoking) in
      childhood and adolescence in a cohort of 2,289 United Kingdom subjects. Data from
      two questionnaires assessing wheezing at ages 7-8 and 15-17 years and one
      questionnaire on current and past pollutant exposures at age 16-18 years were
      studied (1987-1996). The 1,868 subjects returning all three questionnaires were
      divided into three groups representing childhood (10.5%), adolescent (10.9%), and
      persistent (i.e., both; 16.3%) wheezing and compared with 1,165 controls (62.4%)
      without wheezing. The estimated risks of childhood wheezing were increased by
      exposure to any gas in childhood (odds ratio (OR) = 1.47, 95% confidence interval
      (CI): 1.05, 2.04) and exposure to a gas hob in childhood (OR = 1.56, 95% CI:
      1.13, 2.16) and were increased further in those persistently exposed. Risk of
      persistent wheezing in adolescence was paradoxically reduced by exposure to a gas
      hob (OR = 0.67, 95% CI: 0.50, 0.91), possibly because of selection avoidance.
      Contemporaneous exposure to combined smoking by both parents was associated with
      wheezing in all groups (odds ratios ranged from 1.62 (95% CI: 1.06, 2.46) to 1.93
      (95% CI: 1.10, 3.38)). Maternal smoking alone was associated with persistent
      wheezing and with both childhood (OR = 1.90, 95% CI: 1.06, 3.39) and persistent
      (OR = 2.18, 95% CI: 1.15, 4.14) wheezing if smoking occurred throughout childhood
      and adolescence. The authors conclude that exposures to gas cooking and smoking
      in childhood and adolescence increase the overall risk of wheezing.

PMID- 16093294
TI  - Helicobacter pylori and overweight status in the United States: data from the
      Third National Health and Nutrition Examination Survey.
AB  - Obesity is an important public health problem in the United States. Because of
      its potential effects on gastric leptin homeostasis, Helicobacter pylori may play
      a role in regulating body weight. The authors' aim in this study was to examine
      the association between H. pylori colonization and overweight status. Nonpregnant
      participants in the Third National Health and Nutrition Examination Survey (1988
      1994) aged > or = 20 years who had had H. pylori testing performed and body mass
      index (weight (kg)/height (m2)) measured were studied. Overweight was defined as
      a body mass index greater than or equal to 25. On the basis of serologic results,
      the participants were categorized into three H. pylori status groups: H. pylori
      positive and cytotoxin-associated gene A (cagA)-positive (H. pylori+ cagA+), H.
      pylori-positive and cagA-negative (H. pylori+ cagA-), and H. pylori-negative (H.
      pylori-). Of the 7,003 subjects with complete body mass index and H. pylori data,
      2,634 (weighted percentage, 22.9%) were H. pylori+ cagA+, 1,385 (15.1%) were H.
      pylori+ cagA-, and 2,984 (62.0%) were H. pylori-. The adjusted odds of being
      overweight were 1.17 (95% confidence interval: 0.98, 1.39; p = 0.075) for the H.
      pylori+ cagA+ group and 0.99 (95% confidence interval: 0.80, 1.22; p = 0.92) for
      the H. pylori+ cagA- group in comparison with H. pylori- subjects. Serum leptin
      levels did not differ significantly between the three H. pylori groups. In this
      US population-based study, there was no significant association between H. pylori
      colonization, cagA+ strains of H. pylori, and being overweight.

PMID- 16093295
TI  - Decrements in lung function related to arsenic in drinking water in West Bengal,
      India.
AB  - During 1998-2000, the authors investigated relations between lung function,
      respiratory symptoms, and arsenic in drinking water among 287 study participants,
      including 132 with arsenic-caused skin lesions, in West Bengal, India. The source
      population involved 7,683 participants who had been surveyed for arsenic-related
      skin lesions in 1995-1996. Respiratory symptoms were increased among men with
      arsenic-caused skin lesions (versus those without lesions), particularly
      "shortness of breath at night" (odds ratio (OR) = 2.8, 95% confidence interval
      (CI): 1.1, 7.6) and "morning cough" (OR = 2.8, 95% CI: 1.2, 6.6) in smokers and
      "shortness of breath ever" (OR = 3.8, 95% CI: 0.7, 20.6) in nonsmokers. Among men
      with skin lesions, the average adjusted forced expiratory volume in 1 second
      (FEV1) was reduced by 256.2 ml (95% CI: 113.9, 398.4; p < 0.001) and the average
      adjusted forced vital capacity (FVC) was reduced by 287.8 ml (95% CI: 134.9,
      440.8; p < 0.001). In men, a 100-microg/liter increase in arsenic level was
      associated with a 45.0-ml decrease (95% CI: 6.2, 83.9) in FEV1 (p = 0.02) and a
      41.4-ml decrease (95% CI: -0.7, 83.5) in FVC (p = 0.054). Women had lower risks
      than men of developing skin lesions and showed little evidence of respiratory
      effects. In this study, consumption of arsenic-contaminated water was associated
      with respiratory symptoms and reduced lung function in men, especially among
      those with arsenic-related skin lesions.

PMID- 16093297
TI  - Invited commentary: Considering bias in the assessment of respiratory symptoms
      among residents of Lower Manhattan following the events of September 11, 2001.

PMID- 16093298
TI  - Periconceptional smoking and male:female ratio of newborns.
AB  - We have analysed data collected on 1962 women who gave birth at 37 or more weeks
      of gestation to health infants (excluding those with a low birth weight and
      twins). In comparison with non-smoking parents, the odds ratio (OR) of being male
      was lower than unity for offsprings of both smoking parents, but no clear
      relationship however emerged between the risk of giving birth to a male, and the
      number of cigarettes smoked per day.

PMID- 16093299
TI  - Parent-child relationships and health problems in adulthood in three UK national
      birth cohort studies.
AB  - BACKGROUND: Event-based measures suggest that emotional adversity in childhood
      has a long-term health impact, but less attention has been paid to chronic
      emotional stressors such as family conflict, harsh discipline or lack of
      affection. This study aimed to assess the impact of the latter on health problems
      and illness in adulthood. METHODS: Logistic regression and multinomial logistic
      regression analyses of data collected in three UK national birth cohort studies
      at ages 43 and 16 years covering subjective report of relationship quality from
      the 'child', and number of health problems and illnesses reported in adulthood at
      ages 43, 33 and 26 years adjusted for social class, sex and, in 1946 and 1970
      cohorts, for symptoms of mental illness. RESULTS: Reports of abuse and neglect
      (1946 cohort), poor quality relationship with mother and father (1958 cohort),
      and a range of negative relationship descriptors (1970 cohort) predicted reports
      of three or more illnesses or health problems in adulthood. Results were
      inconsistent with respect to one or two illnesses or health problems. Adjustment
      for sex, social class and poor mental health attenuated the odds of poor health,
      but measures of relationship quality retained a significant independent effect.
      CONCLUSIONS: Poor quality parent-child relationships could be a remediable risk
      factor for poor health in adulthood.

PMID- 16093300
TI  - Advice to patients in Swedish primary care regarding alcohol and other lifestyle
      habits: how patients report the actions of GPs in relation to their own
      expectations and satisfaction with the consultation.
AB  - BACKGROUND: Lifestyle advice given by general practitioners (GPs) may be a cost
      effective means of health promotion; however, it is not fully put into routine
      practice. The aim of this study was to explore to what extent GPs' patients
      expect and receive advice concerning alcohol, tobacco, exercise and diet in
      relation to sociodemographic characteristics, type of visit and patient
      satisfaction. METHODS: A postal questionnaire was sent to a representative sample
      (n = 9750) of patients who had consulted GPs in a county in Sweden. The response
      rate was 69% (n = 6734). RESULTS: Exercise was the most (16%) and alcohol the
      least (5%) common type of advice. The patients received advice more often than
      they expected in all areas except alcohol. The patients reported the highest rate
      of unfulfilled advice expectation and the lowest rate of unexpected advice in the
      case of alcohol. Male gender, poorer self-rated health and scheduled appointment
      were independent predictors of all types of advice. Continuity of GP contact was
      only favourable for exercise and diet advice. The patients who received advice
      were more satisfied with their visit to the doctor. CONCLUSIONS: A tertiary
      preventive perspective guides GPs' practice of giving advice. Male patients with
      advanced illnesses are given priority. Women and patients with long-term risk
      habits are more neglected. The GPs tend to misjudge the expectations and needs of
      their patients and are too restrained in their counselling practice. Alcohol is
      the most disregarded area of advice in proportion to the patients' expectations
      and needs.

PMID- 16093301
TI  - Prevalence of hepatitis A among drug users in north-eastern Italy. Is vaccination
      necessary in low prevalence areas?
AB  - BACKGROUND: The authors report on the prevalence of, and risk factors for,
      hepatitis A virus (HAV) in a group of drug users in Italy. METHODS: 404 heroin
      users were recruited and compared with a control group of 107 subjects in the
      general population. RESULTS: Drug users born in north-eastern Italy have a
      prevalence of anti-HAV similar to the control group. A much higher prevalence was
      found in drug users born in southern Italy. CONCLUSION: The similar prevalence of
      anti-HAV in drug users born in north-eastern Italy and in the general population,
      suggests that their lifestyle does not involve a substantial additional risk of
      HAV. The much higher prevalence found in drug users born in southern Italy is
      more likely to be related to infection during infancy.

PMID- 16093302
TI  - Social inequalities in mortality: changes in the relative importance of income,
      education and household size over a 27-year period.
AB  - BACKGROUND: The aim of this paper was to measure socio-economic inequalities in
      mortality over a 27-year period, and estimate the simultaneous effects of
      education and income adjusted for changing proportions and potential confounders.
      METHODS: Census data in 1970, 1980 and 1990 with information about income,
      educational level and household size were linked to mortality records at the
      individual level and analysed with absolute mortality rates, Poisson regression
      (univariate and multivariate) and Relative Index of Inequality (RII). RESULTS:
      Mortality differences increased between income quartiles and educational groups
      as well as between singles and non-singles. RII between income quartiles
      increased from 1.6 to 3.6 for men and 1.7 to 2.7 for women while RII between the
      educational groups increased from 1.6 to 2.8 for men and 1.5 to 2.1 for women.
      However, RII derived from the adjusted multivariate regression analysis was 1.8
      (men) and 1.9 (women) between the income groups in 1990 and 2.2 (men) and 1.7
      (women) between the educational groups. In the 1990s current income was more
      important than previous income, and the rate ratios (RR) increased for groups
      dropping into the lowest income quartile between two censuses. CONCLUSION: Low
      education and single status have become relatively more important risk factors
      for mortality over time. Confounder effects of education and household size could
      partly explain the seemingly large increase in inequalities between income
      groups. Results may also indicate a stronger reverse causation (poor health
      causing low income) over time.

PMID- 16093303
TI  - The usefulness of area-based socioeconomic measures to monitor social
      inequalities in health in Southern Europe.
AB  - BACKGROUND: The study objective was to investigate the association between health
      outcomes and several small-area-based socioeconomic measures and also with
      individual socioeconomic measures as a check on external validity. METHODS: Cross
      sectional design based on the analysis of the Barcelona Health Interview Survey
      of 1992. A representative stratified sample of the non-institutionalised
      population resident in Barcelona city (Spain) was obtained. The present study
      refers to the 4171 respondents aged over 14. We studied perceived health status,
      presence of chronic conditions and smoking as health outcomes. Area socioeconomic
      measures (1991 census) were generated at census tract level and individual
      socioeconomic measures were educational level and social class obtained through
      the survey. RESULTS: With individual socioeconomic measures we observed that the
      lower the educational level or social class, the higher the probability of
      reporting a perceived health status of fair, poor or very poor and of presenting
      some chronic condition. With regard to smoking, among men this trend was similar
      [odds ratio (OR) = 1.5; 95% confidence interval (CI) = 1.2-1.9 in social classes
      IV-V with respect to social classes I-II], while among women it was reversed (OR
      = 0.7; 95% CI = 0.5-0.9). With the different area-based socioeconomic indicators
      differences were also observed in this sense, with the exception of smoking in
      women for which these indicators do not show any differences by socioeconomic
      level. CONCLUSIONS: With several census area-based socioeconomic measures similar
      effects on inequalities in health have been observed. In general, these
      inequalities were in the same sense as those obtained with individual-based
      measures. Small-area-based socioeconomic measures from the Spanish census could
      greatly enhance analysis of social inequalities in health, overcoming the absence
      of socioeconomic data in public health registries and in medical records.

PMID- 16093304
TI  - Policies to prevent childhood obesity in the European Union.
AB  - The increasing prevalence of childhood obesity needs to be addressed. Without
      clear evidence to show which preventive interventions are most likely to work, a
      series of precautionary measures can be suggested. At a meeting of scientific
      experts organised by the International Obesity TaskForce and held at the European
      Congress on Obesity in May, 2004, a number of measures were proposed which follow
      the precautionary principle of promoting health while being unlikely to increase
      the risk of harm. The proposals are reported in the present paper.

PMID- 16093305
TI  - Effect of grandparent's and parent's socioeconomic position on mortality among
      Danish men born in 1953.
AB  - BACKGROUND: The adverse effect on health of poor social circumstances might
      accumulate not only over the lifespan of the individual but also across
      generations. This study examines the effect of parent's and grandparent's
      socioeconomic position on all-cause mortality of their adult offspring. METHODS:
      2890 males born in the metropolitan area of Copenhagen, Denmark in 1953, whose
      mothers were interviewed for information on family social background in 1968,
      were followed from 1968 to 2002 for information on vital status by record linkage
      to the Civil Registration System. The data were analysed using Cox regression
      models. RESULTS: All-cause mortality from age 15 to 49 years increased 25% [95%
      confidence interval (CI) 13-39%] for each number of parents or grandparents from
      working or unknown occupational social class. Offspring mortality decreased with
      the number of ancestors with a secondary school education hazard ratio [HR = 0.84
      (95% CI 0.76-0.93)]. When the cumulative measures of ancestor's occupation and
      education were included in the same model, the estimates for the effect of
      occupational social class [HR = 1.19 (95% CI 1.06-1.34)] and education [HR = 0.91
      (95% CI 0.80-1.03)] both attenuated. These relations only changed slightly when
      subject's own occupational class at age 22 years was taken into account.
      CONCLUSION: The adverse health effects of disadvantaged social circumstances
      accumulate not only over an individual's lifespan but also across generations.
      Cumulated occupational social class of ancestors seems to be an independent
      predictor of mortality in adult life after adjustment for subject's own social
      class at age 22 years.

PMID- 16093306
TI  - Trends in risk factor control in Germany 1984-1998: high blood pressure and total
      cholesterol.
AB  - BACKGROUND: Diagnosis and treatment of the two primary cardiovascular risk
      factors, hypertension and hypercholesterolaemia, are well established.
      Nevertheless, according to earlier analyses of representative health
      questionnaire and examination surveys in 1984, 1988 and 1991, control of risk
      factors in the sense of normalized values through drug therapy did not improve to
      any relevant degree in former West Germany. The National Health Survey of 1998
      now allows the reconsideration of the hypothesis that medical treatment has been
      improving and lead to a reduction of risk factor values measured in the
      population. METHODS: Datasets of independent cross-sectional studies in 1984,
      1988, 1991 and 1998 with net random sample sizes between 3,458 and 5,335 were
      analysed for actual (persons with elevated values and persons successfully
      treated) and population (persons with elevated values) prevalence, awareness of
      the risk factors under question, treatment coverage (risk factor aware and
      treated) and effectiveness (risk factor aware, treated and normalized), and the
      resulting parameters of controlled (successfully treated persons among actual
      prevalence) and uncontrolled prevalence (persons with elevated values among
      actual prevalence), respectively. Thresholds chosen were blood pressure values
      >or=160/95 mmHg for hypertension and values >or=250 mg/dl for
      hypercholesterolaemia. Regarding medication, the answer of 'one to two times
      weekly' or more was considered to indicate a relevant drug intake. RESULTS: For
      hypertension the population prevalence (population 30-69 years old) increased
      significantly (P < 0.0001) from 19.6% to 24.0% between 1984 and 1998, whereas the
      actual prevalence rose less steeply but still significantly (P < 0.0002) from
      32.5% to 34.4%. For hypercholesterolaemia the population prevalence stagnated at
      37.0% (1998), whereas the actual prevalence was 47.5% in 1998 (39.1% in 1984; P <
      0.0001). For hypertension treatment, coverage improved from 45.4% to 63.0%, but
      treatment effectiveness decreased from 51.7% to 41.3%, both trends being highly
      significant. For hypercholesterolaemia, awareness increased from 18.3% to 57.6%,
      but treatment coverage decreased from 33.5% to 15.5%, whereas treatment
      effectiveness improved from 23.8% to 47.7%, all trends being highly significant
      (P < 0.0001). CONCLUSIONS: The results do not support the hypothesis that medical
      care for the large population at cardiovascular risk in (Western) Germany was
      adequate and successful in the 1980s and 1990s.

PMID- 16093307
TI  - Ten-year incidence and time trends of railway suicides in Germany from 1991 to
      2000.
AB  - BACKGROUND: Railway suicides strongly impact psychological and socioeconomic
      aspects of the railway company, its employees and possible eye witnesses. We
      aimed to assess the incidence of railway suicides compared with the total burden
      of suicides in Germany and its time trend over a 10-year observation period.
      METHODS: From 1991 to 2000, a total of 8,653 fatal railway suicides were recorded
      by the national central registry of all passenger accidents on the German railway
      net. To assess time trends, the average annual percentage change (AAPC) of the
      number of suicides was estimated using Poisson regression. Adjustments were made
      for two age groups and measures of availability. RESULTS: Railway suicides
      accounted for 7.0% (annual range 5.0-7.9%) of all suicides in Germany. The time
      trend of the number of suicides by all means declined, with a significant
      stronger decline for older subjects [AAPC -2.2; 95% confidence intercal (CI) -3.0
      to -1.5; and -4.2; 95% CI -5.2 to -3.0]. An AAPC of 1.8% (95% CI 0.1-3.4)
      indicated an increasing time trend of the number of railway suicides for subjects
      aged <or=65 years, whereas, in contrast, fatal incidences for subjects aged >65
      years exhibited a strong decrease (AAPC -6.2%; 95% CI -10.9 to -1.3).
      CONCLUSIONS: The present study demonstrates different time trends for railway
      suicides compared with all suicides. It underlines the urgent need for amplified
      research efforts in the particular field of railway suicides. Further
      examinations are recommended, in particular concerning possible reasons for this
      suicidal method.

PMID- 16093308
TI  - HOXB4 enforces equivalent fates of ES-cell-derived and adult hematopoietic cells.
AB  - Genetic manipulation of hematopoietic stem and progenitor cells is an important
      tool for experimental and clinical applied hematology. However, techniques that
      allow for gene targeting, subsequent in vitro selection, and expansion of
      genetically defined clones are available only for ES cells. Such molecularly
      defined and, hence, "safe" clones would be highly desirable for somatic gene
      therapy. Here, we demonstrate that in vitro differentiated ES cells completely
      recapitulate the growth and differentiation properties of adult bone marrow
      cells, in vitro and in vivo, when ectopically expressing HOXB4. Myeloid
      development was enforced and (T) lymphoid development suppressed over a wide
      range of expression levels, whereas only high expression levels of the
      transcription factor were detrimental for erythroid development. This indicates a
      close association between the amounts of ectopic HOXB4 present within a
      progenitor cell and and the decision to self renew or differentiate. Because
      HOXB4 mediates similar fates of ES-derived and bone marrow hematopoietic stem
      cells, the primitive embryonic cells can be considered a promising alternative
      for investigating hematopoietic reconstitution, in vivo, based on well defined
      clones. Provided that HOXB4 levels are kept within a certain therapeutic window,
      ES cells also carry the potential of efficient and safe somatic gene therapy.

PMID- 16093309
TI  - Alpha1-antitrypsin monotherapy prolongs islet allograft survival in mice.
AB  - Islet transplantation for type 1 diabetic patients shows promising results with
      the use of nondiabetogenic immunosuppressive therapy. However, in addition to
      compromising the immune system of transplant recipients, long-term studies
      demonstrate that islet viability is impaired. Here, we demonstrate that, in the
      absence of immunosuppressive agents, monotherapy with clinical-grade human alpha1
      antitrypsin (hAAT), the major serum serine-protease inhibitor, prolongs islet
      graft survival and normoglycemia in transplanted allogeneic diabetic mice,
      lasting until the development of anti-hAAT antibodies. Compared to untreated or
      albumin-control-treated graft recipients, which rejected islets at day 10, AAT
      treated mice displayed diminished cellular infiltrates and intact intragraft
      insulin production throughout treatment. Using peritoneal infiltration models, we
      demonstrate that AAT decreases allogeneic fibroblast-elicited natural-killer-cell
      influx by 89%, CD3-positive cell influx by 44%, and thioglycolate-elicited
      neutrophil emigration by 66%. ATT also extended islet viability in mice after
      streptozotocin-induced beta cell toxicity. In vitro, several islet responses to
      IL-1beta/IFNgamma stimulation were examined. In the presence of AAT, islets
      displayed enhanced viability and inducible insulin secretion. Islets also
      released 36% less nitric oxide and 82% less macrophage inflammatory protein 1
      alpha and expressed 63% fewer surface MHC class II molecules. TNFalpha release
      from IL-1beta/IFNgamma-stimulated islet cells was reduced by 99%, accompanied by
      an 8-fold increase in the accumulation of membrane TNFalpha on CD45-positive
      islet cells. In light of the established safety record and the nondiabetogenic
      potential of AAT, these data suggest that AAT may be beneficial as adjunctive
      therapy in patients undergoing islet transplantation.

PMID- 16093310
TI  - Large-scale identification of yeast integral membrane protein interactions.
AB  - We carried out a large-scale screen to identify interactions between integral
      membrane proteins of Saccharomyces cerevisiae by using a modified split-ubiquitin
      technique. Among 705 proteins annotated as integral membrane, we identified 1,985
      putative interactions involving 536 proteins. To ascribe confidence levels to the
      interactions, we used a support vector machine algorithm to classify interactions
      based on the assay results and protein data derived from the literature.
      Previously identified and computationally supported interactions were used to
      train the support vector machine, which identified 131 interactions of highest
      confidence, 209 of the next highest confidence, 468 of the next highest, and the
      remaining 1,085 of low confidence. This study provides numerous putative
      interactions among a class of proteins that have been difficult to analyze on a
      high-throughput basis by other approaches. The results identify potential
      previously undescribed components of established biological processes and roles
      for integral membrane proteins of ascribed functions.

PMID- 16093311
TI  - Blockade of calcium-permeable AMPA receptors protects hippocampal neurons against
      global ischemia-induced death.
AB  - Transient global or forebrain ischemia induced experimentally in animals can
      cause selective, delayed neuronal death of hippocampal CA1 pyramidal neurons. A
      striking feature is a delayed rise in intracellular free Zn(2+) in CA1 neurons
      just before the onset of histologically detectable cell death. Here we show that
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate
      receptors (AMPARs) at Schaffer collateral to CA1 synapses in postischemic
      hippocampus exhibit properties of Ca(2+)/Zn(2+)-permeable, Glu receptor 2 (GluR2)
      lacking AMPARs before the rise in Zn(2+) and cell death. At 42 h after ischemia,
      AMPA excitatory postsynaptic currents exhibited pronounced inward rectification
      and marked sensitivity to 1-naphthyl acetyl spermine (Naspm), a selective channel
      blocker of GluR2-lacking AMPARs. In control hippocampus, AMPA excitatory
      postsynaptic currents were electrically linear and relatively insensitive to
      Naspm. Naspm injected intrahippocampally at 9-40 h after insult greatly reduced
      the late rise in intracellular free Zn(2+) in postischemic CA1 neurons and
      afforded partial protection against ischemia-induced cell death. These results
      implicate GluR2-lacking AMPA receptors in the ischemia-induced rise in free
      Zn(2+) and death of CA1 neurons, although a direct action at the time of the rise
      in Zn(2+) is unproven. This receptor subtype appears to be an important
      therapeutic target for intervention in ischemia-induced neuronal death in humans.

PMID- 16093312
TI  - Vitamin A and immune function: retinoic acid modulates population dynamics in
      antigen receptor and CD38-stimulated splenic B cells.
AB  - Vitamin A and its active metabolite, all-trans retinoic acid (RA), regulate the
      antibody response in vivo, although the underlying mechanisms are not well
      understood. We have investigated the regulation by RA of B cell population
      dynamics and Ig gene expression in purified splenic mouse B cells stimulated
      through the B cell antigen receptor (BCR) and/or CD38, a BCR coreceptor. After
      ligation of the BCR and/or CD38, B cells became more heterogeneous in size. RA
      substantially restrained this change, concomitant with inhibition of cell
      proliferation. To examine B cell heterogeneity more closely, we categorized
      stimulated B cells by size (forward angle light scatter) and determined cell
      division dynamics, germ-line Ig heavy chain gene transcription and surface IgG1
      (sIgG1) expression. Flow cytometric analysis of carboxyfluorescein diacetate
      succinimidyl ester-labeled B cells costained for sIgG1 showed that the more
      proliferative groups of B cells were smaller, whereas cells expressing more sIgG1
      were larger. RA enriched the latter population, whereas cell division frequency
      in general and the number of smaller B cells that had undergone division cycles
      were reduced. Although RA significantly inhibited Ig germ-line transcript levels
      in the total B cell population, CD19(-)IgG1(+) B cells, which represent a more
      differentiated phenotype, were enriched. Furthermore, pax-5 mRNA was decreased
      and activation-induced cytidine deaminase mRNA was increased in RA-treated
      stimulated B cells. Thus, RA regulated factors known to be required for Ig class
      switch recombination and modulated the population dynamics of ligation-stimulated
      B cells, while promoting the progression of a fraction of B cells into
      differentiated sIgG-expressing cells.

PMID- 16093313
TI  - Specific inhibition of CBP/beta-catenin interaction rescues defects in neuronal
      differentiation caused by a presenilin-1 mutation.
AB  - Wnt/beta-catenin signaling has been shown to promote self-renewal in a variety of
      tissue stem cells, including neuronal stem cells and hematopoietic stem cells.
      However, activation of the Wnt/beta-catenin pathway promoted and inhibition of
      the pathway prevented differentiation of neuronal precursor cells. A clear
      explanation for the differential effects of Wnt/beta-catenin activation on
      neuronal precursors is not available at present. Presenilin-1 (PS-1) is a
      polytopic protein comprised of six to eight transmembrane domains. PS-1, as part
      of the gamma-secretase complex, is required for the intramembrane proteolysis of
      both amyloid precursor protein (APP) and Notch. Additionally, through
      interactions with beta-catenin, PS-1 is associated with modulation of Wnt/beta
      catenin signaling. A familial Alzheimer's disease-associated PS-1 mutant, PS
      1(L286V), causes a dramatic increase in T cell factor (TCF)/beta-catenin
      transcription in PC-12 cells, which prevents normal nerve growth factor (NGF)
      induced neuronal differentiation and neurite outgrowth. Selective inhibition of
      TCF/beta-catenin/cAMP-response element-binding protein (CREB)-binding protein
      (CBP)-mediated transcription, but not TCF/beta-catenin/p300, with the recently
      described small molecule antagonist ICG-001 corrects these defects in neuronal
      differentiation, highlighting the importance of Wnt/beta-catenin signaling in
      this process. We propose that increased TCF/beta-catenin/CBP-mediated
      transcription, as well as a failure to switch to TCF/beta-catenin/p300-mediated
      transcription, play an important role in decreasing neuronal differentiation.

PMID- 16093314
TI  - Atomic resolution structures of resting-state, substrate- and product-complexed
      Cu-nitrite reductase provide insight into catalytic mechanism.
AB  - Copper-containing nitrite reductases catalyze the reduction of nitrite to nitric
      oxide (NO), a key step in denitrification that results in the loss of terrestrial
      nitrogen to the atmosphere. They are found in a wide variety of denitrifying
      bacteria and fungi of different physiology from a range of soil and aquatic
      ecosystems. Structural analysis of potential intermediates in the catalytic cycle
      is an important goal in understanding enzyme mechanism. Using "crystal
      harvesting" and substrate-soaking techniques, we have determined atomic
      resolution structures of four forms of the green Cu-nitrite reductase, from the
      soil bacterium Achromobacter cycloclastes. These structures are the resting state
      of the enzyme at 0.9 A, two species exhibiting different conformations of nitrite
      bound at the catalytic type 2 Cu, one of which is stable and also has NO present,
      at 1.10 A and 1.15 A, and a stable form with the product NO bound side-on to the
      catalytic type 2 Cu, at 1.12 A resolution. These structures provide incisive
      insights into the initial binding of substrate, its repositioning before
      catalysis, bond breakage (O-NO), and the formation of a stable NO adduct.

PMID- 16093315
TI  - Beyond affect: a role for genetic variation of the serotonin transporter in
      neural activation during a cognitive attention task.
AB  - Prior work has highlighted the role of genetic variation within the repetitive
      sequence in the transcriptional control region of the serotonin (5-HT)
      transporter gene (5-HTT, SLC6A4) in modulating amygdala and prefrontal activation
      to negative emotional stimuli. However, these studies have not explicitly tested
      the assumption that the control condition (neutral baseline) does not itself
      produce changes in activation as a function of 5-HTT genotype. Using a fixation
      baseline condition, we show that variation in 5-HTT genotype is associated with
      differential activation to negative, positive, and neutral stimuli in limbic,
      striatal, and cortical regions. We replicate earlier reports of increased
      amygdala activation to negative, relative to neutral, stimuli, but then show that
      these differences are driven by decreased activation to neutral stimuli, rather
      than increased activation to negative stimuli, in carriers of the 5-HTT short
      allele. Using high-resolution structural images and automated processes to test
      for brain volume and gray matter density, we further report significant
      differences, as a function of 5-HTT genotype, in frontal cortical regions,
      anterior cingulate, and cerebellum. These functional and structural differences
      suggest a much broader role for 5-HT transport efficiency in brain processes than
      previously thought. 5-HTT genotype affects neural systems controlling affective,
      cognitive, and motor processes.

PMID- 16093316
TI  - Absence of detectable transgenes in local landraces of maize in Oaxaca, Mexico
      (2003-2004).
AB  - In 2000, transgenes were detected in local maize varieties (landraces) in the
      mountains of Oaxaca, Mexico [Quist, D. & Chapela, I. H. (2001) Nature 414, 541
      543]. This region is part of the Mesoamerican center of origin for maize (Zea
      mays L.), and the genetic diversity that is maintained in open-pollinated
      landraces is recognized as an important genetic resource of great cultural value.
      The presence of transgenes in landraces was significant because transgenic maize
      has never been approved for cultivation in Mexico. Here we provide a systematic
      survey of the frequency of transgenes in currently grown landraces. We sampled
      maize seeds from 870 plants in 125 fields and 18 localities in the state of
      Oaxaca during 2003 and 2004. We then screened 153,746 sampled seeds for the
      presence of two transgene elements from the 35S promoter of the cauliflower
      mosaic virus and the nopaline synthase gene (nopaline synthase terminator) from
      Agrobacterium tumefaciens. One or both of these transgene elements are present in
      all transgenic commercial varieties of maize. No transgenic sequences were
      detected with highly sensitive PCR-based markers, appropriate positive and
      negative controls, and duplicate samples for DNA extraction. We conclude that
      transgenic maize seeds were absent or extremely rare in the sampled fields. This
      study provides a much-needed preliminary baseline for understanding the
      biological, socioeconomic, and ethical implications of the inadvertent dispersal
      of transgenes from the United States and elsewhere to local landraces of maize in
      Mexico.

PMID- 16093317
TI  - High-frequency gene targeting in Arabidopsis plants expressing the yeast RAD54
      gene.
AB  - Gene targeting, which is homologous recombination-mediated integration of an
      extra-chromosomal DNA segment into a chromosomal target sequence, enables the
      precise disruption or replacement of any gene. Despite its value as a molecular
      genetic tool, gene targeting remains an inefficient technology in most species.
      We report that expression of the yeast RAD54 gene, a member of the SWI2/SNF2
      chromatin remodeling gene family, enhances gene targeting in Arabidopsis by one
      to two orders of magnitude, from 10(-4) to 10(-3) in WT plants to 10(-2) to 10(
      1). We show that integration events, detected with an assay based on the use of a
      fluorescent seed marker, are precise and germinally transmitted. These findings
      suggest that chromatin remodeling is rate-limiting for gene targeting in plants
      and improves the prospects for using gene targeting for the precise modification
      of plant genomes.

PMID- 16093318
TI  - Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock,
      regulates adipogenesis.
AB  - Brain and muscle Arnt-like protein-1 (BMAL1; also known as MOP3 or Arnt3) is a
      transcription factor known to regulate circadian rhythm. Here, we established its
      involvement in the control of adipogenesis and lipid metabolism activity in
      mature adipocytes. During adipose differentiation in 3T3-L1 cells, the level of
      BMAL1 mRNA began to increase 4 days after induction and was highly expressed in
      differentiated cells. In white adipose tissues isolated from C57BL/6J mice, BMAL1
      was predominantly expressed in a fraction containing adipocytes, as compared with
      the stromal-vascular fraction. BMAL1 knockout mice embryonic fibroblast cells
      failed to be differentiated into adipocytes. Importantly, adding BMAL1 back by
      adenovirus gene transfer restored the ability of BMAL1 knockout mice embryonic
      fibroblast cells to differentiate. Knock-down of BMAL1 expression in 3T3-L1 cells
      by an RNA interference technique allowed the cells to accumulate only minimum
      amounts of lipid droplets in the cells. Adenovirus-mediated expression of BMAL1
      in 3T3-L1 adipocytes resulted in induction of several factors involved in
      lipogenesis. The promoter activity of these genes was stimulated in a BMAL1
      dependent manner. Interestingly, expression of these factors showed clear
      circadian rhythm in mice adipose tissue. Furthermore, overexpression of BMAL1 in
      adipocytes increased lipid synthesis activity. These results indicate that BMAL1,
      a master regulator of circadian rhythm, also plays important roles in the
      regulation of adipose differentiation and lipogenesis in mature adipocytes.

PMID- 16093319
TI  - From The Cover: A role for Arabidopsis cryptochromes and COP1 in the regulation
      of stomatal opening.
AB  - Cryptochromes (CRY) are blue light photoreceptors that mediate various light
      induced responses in plants and animals. Arabidopsis CRY (CRY1 and CRY2)
      functions through negatively regulating constitutive photomorphogenic (COP) 1, a
      repressor of photomorphogenesis. Water evaporation and photosynthesis are
      regulated by the stomatal pores in plants, which are closed in darkness but open
      in response to blue light. There is evidence only for the phototropin blue light
      receptors (PHOT1 and PHOT2) in mediating blue light regulation of stomatal
      opening. Here, we report a previously uncharacterized role for Arabidopsis CRY
      and COP1 in the regulation of stomatal opening. Stomata of the cry1 cry2 double
      mutant showed reduced blue light response, whereas those of the CRY1
      overexpressing plants showed hypersensitive response to blue light. In addition,
      stomata of the phot1 phot2 double mutant responded to blue light, but those of
      the cry1 cry2 phot1 phot2 quadruple mutant hardly responded. Strikingly, stomata
      of the cop1 mutant were constitutively open in darkness and stomata of the cry1
      cry2 cop1 and phot1 phot2 cop1 triple mutants were open as wide as those of the
      cop1 single mutant under blue light. These results indicate that CRY functions
      additively with PHOT in mediating blue light-induced stomatal opening and that
      COP1 is a repressor of stomatal opening and likely acts downstream of CRY and
      PHOT signaling pathways.

PMID- 16093320
TI  - Preventing local regeneration of glucocorticoids by 11beta-hydroxysteroid
      dehydrogenase type 1 enhances angiogenesis.
AB  - Angiogenesis restores blood flow to healing tissues, a process that is inhibited
      by high doses of glucocorticoids. However, the role of endogenous glucocorticoids
      and the potential for antiglucocorticoid therapy to enhance angiogenesis is
      unknown. Using in vitro and in vivo models of angiogenesis in mice, we examined
      effects of (i) endogenous glucocorticoids, (ii) blocking endogenous
      glucocorticoid action with the glucocorticoid receptor antagonist RU38486, and
      (iii) abolishing local regeneration of glucocorticoids by the enzyme 11beta
      hydroxysteroid dehydrogenase type 1 (11betaHSD1). Glucocorticoids, administered
      at physiological concentrations, inhibited angiogenesis in an in vitro aortic
      ring model and in vivo in polyurethane sponges implanted s.c. RU38486-enhanced
      angiogenesis in s.c. sponges, in healing surgical wounds, and in the myocardium
      of mice 7 days after myocardial infarction induced by coronary artery ligation.
      11betaHSD1 knockout mice showed enhanced angiogenesis in vitro and in vivo within
      sponges, wounds, and infarcted myocardium. Endogenous glucocorticoids, including
      those generated locally by 11betaHSD1, exert tonic inhibition of angiogenesis.
      Inhibition of 11betaHSD1 in liver and adipose has been advocated to reduce
      cardiovascular risk in the metabolic syndrome: these data suggest that 11betaHSD1
      inhibition offers a previously uncharacterized therapeutic approach to improve
      healing of ischemic or injured tissue.

PMID- 16093321
TI  - In vivo transcriptional regulation of N-Myc target genes is controlled by E-box
      methylation.
AB  - N-Myc is a transcription factor that forms heterodimers with the protein Max and
      binds gene promoters by recognizing a DNA sequence, CACGTG, called E-box. The
      identification of N-myc target genes is an important step for understanding N-Myc
      biological functions in both physiological and pathological contexts. In this
      study, we describe the identification of N-Myc-responsive genes through chromatin
      immunoprecipitation and methylation-sensitive restriction analysis. Results show
      that N-Myc is a direct regulator of several identified genes, and that
      methylation of the CpG dinucleotide within the E-box prevents the access of N-Myc
      to gene promoters in vivo. Furthermore, methylation profile of the E-box within
      the promoters of EGFR and CASP8, two genes directly controlled by Myc, is cell
      type-specific, suggesting that differential E-box methylation may contribute to
      generating unique patterns of Myc-dependent transcription. This study illuminates
      a central role of DNA methylation in controlling N-Myc occupancy at gene
      promoters and modulating its transcriptional activity in cancer cells.

PMID- 16093322
TI  - RNF17, a component of the mammalian germ cell nuage, is essential for
      spermiogenesis.
AB  - Nuages are found in the germ cells of diverse organisms. However, nuages in
      postnatal male germ cells of mice are poorly studied. Previously, we cloned a
      germ cell-specific gene named Rnf17, which encodes a protein containing both a
      RING finger and tudor domains. Here, we report that RNF17 is a component of a
      novel nuage in male germ cells--the RNF17 granule, which is an electron-dense non
      membrane bound spherical organelle with a diameter of 0.5 mum. RNF17 granules are
      prominent in late pachytene and diplotene spermatocytes, and in elongating
      spermatids. RNF17 granules are distinguishable from other known nuages, such as
      chromatoid bodies. RNF17 is able to form dimers or polymers both in vitro and in
      vivo, indicating that it may play a role in the assembly of RNF17 granules. Rnf17
      deficient male mice were sterile and exhibited a complete arrest in round
      spermatids, demonstrating that Rnf17 encodes a novel key regulator of
      spermiogenesis. Rnf17-null round spermatids advanced to step 4 but failed to
      produce sperm. These results have shown that RNF17 is a component of a novel germ
      cell nuage and is required for differentiation of male germ cells.

PMID- 16093323
TI  - The interplay between DSL proteins and ubiquitin ligases in Notch signaling.
AB  - Lateral inhibition is a pattern refining process that generates single neural
      precursors from a field of equipotent cells and is mediated via Notch signaling.
      Of the two Notch ligands Delta and Serrate, only the former was thought to
      participate in this process. We now show that macrochaete lateral inhibition
      involves both Delta and Serrate. In this context, Serrate interacts with
      Neuralized, a ubiquitin ligase that was heretofore thought to act only on Delta.
      Neuralized physically associates with Serrate and stimulates its endocytosis and
      signaling activity. We also characterize a mutation in mib1, a Drosophila homolog
      of mind bomb, another Delta-targeting ubiquitin ligase from zebrafish. Mib1
      affects the signaling activity of Delta and Serrate in both lateral inhibition
      and wing dorsoventral boundary formation. Simultaneous absence of neuralized and
      mib1 completely abolishes Notch signaling in both aforementioned contexts, making
      it likely that ubiquitination is a prerequisite for Delta/Serrate signaling.

PMID- 16093324
TI  - Mutual repression between msh and Iro-C is an essential component of the boundary
      between body wall and wing in Drosophila.
AB  - During development, the imaginal wing disc of Drosophila is subdivided into
      territories separated by developmental boundaries. The best characterized
      boundaries delimit compartments defined by cell-lineage restrictions. Here, we
      analyze the formation of a boundary that does not rely on such restrictions,
      namely, that which separates the notum (body wall) and the wing hinge
      (appendage). It is known that the homeobox genes of the Iroquois complex (Iro-C)
      define the notum territory and that the distal limit of the Iro-C expression
      domain demarks the boundary between the notum and the wing hinge. However, it is
      unclear how this boundary is established and maintained. We now find that msh, a
      homeobox gene of the Msx family, is strongly expressed in the territory of the
      hinge contiguous to the Iro-C domain. Loss- and gain-of-function analyses show
      that msh maintains Iro-C repressed in the hinge, while Iro-C prevents high level
      expression of msh in the notum. Thus, a mutual repression between msh and Iro-C
      is essential to set the limit between the contiguous domains of expression of
      these genes and therefore to establish and/or maintain the boundary between body
      wall and wing. In addition, we find that msh is necessary for proper growth of
      the hinge territory and the differentiation of hinge structures. msh also
      participates in the patterning of the notum, where it is expressed at low levels.

PMID- 16093325
TI  - A balance of FGF, BMP and WNT signalling positions the future placode territory
      in the head.
AB  - The sensory nervous system in the vertebrate head arises from two different cell
      populations: neural crest and placodal cells. By contrast, in the trunk it
      originates from neural crest only. How do placode precursors become restricted
      exclusively to the head and how do multipotent ectodermal cells make the decision
      to become placodes or neural crest? At neural plate stages, future placode cells
      are confined to a narrow band in the head ectoderm, the pre-placodal region
      (PPR). Here, we identify the head mesoderm as the source of PPR inducing signals,
      reinforced by factors from the neural plate. We show that several independent
      signals are needed: attenuation of BMP and WNT is required for PPR formation.
      Together with activation of the FGF pathway, BMP and WNT antagonists can induce
      the PPR in naive ectoderm. We also show that WNT signalling plays a crucial role
      in restricting placode formation to the head. Finally, we demonstrate that the
      decision of multipotent cells to become placode or neural crest precursors is
      mediated by WNT proteins: activation of the WNT pathway promotes the generation
      of neural crest at the expense of placodes. This mechanism explains how the
      placode territory becomes confined to the head, and how neural crest and placode
      fates diversify.

PMID- 16093326
TI  - Potassium currents in isolated statocyst neurons and RPeD1 in the pond snail,
      Lymnaea stagnalis.
AB  - To begin to determine the underlying neural mechanisms of memory formation, we
      studied two different cell types that play important roles in different forms of
      associative learning in Lymnaea. Statocyst neurons (hair cells) mediate classical
      conditioning, whereas RPeD1 is a site of memory formation induced by operant
      conditioning of aerial respiration. Because potassium (K(+)) channels play a
      critical role in neuronal excitability, we initiated studies on these channels in
      the aforementioned neurons. Three distinct K(+) currents are expressed in the
      soma of both the hair cells and RPeD1. In hair cells and RPeD1, there is a fast
      activating and rapidly inactivating 4-aminopyridine (4-AP)-sensitive A current
      (I(A)), a tetraethyl ammonium (TEA)-sensitive delayed rectifying current, which
      exhibits slow inactivation kinetics (I(KV)), and a TEA- and 4-AP-insensitive
      Ca(2+)-dependent current (I(Ca-K)). In hair cells, the activation voltage of
      I(A); its half-maximal steady-state activation voltage and its half-maximal
      steady-state inactivation were at more depolarized levels than in RPeD1. The time
      constant of recovery from I(A) inactivation was slightly faster in hair cells.
      I(A) in hair cells is also smaller in amplitude than in RPeD1 and is activated at
      more depolarized potentials. In like manner, I(KV) is smaller in hair cells and
      is activated at more depolarized potentials than in RPeD1.

PMID- 16093327
TI  - Role of motor and visual experience during development of bipedal locomotion in
      chicks.
AB  - The purpose of this research was to investigate the role of motor and visual
      experience during the development of locomotion in chicks. We have previously
      demonstrated that when locomotor activity is restricted immediately posthatching,
      chicks walk with shorter stride lengths and attenuated head bobbing movements.
      Head bobbing is an optokinetic response in birds, driven by the movement of the
      visual world across the retina (i.e., optic flow). During locomotion, optic flow
      is generated by forward translation, and we have shown that the magnitude of head
      bobbing movements and stride lengths are moderately correlated in walking chicks.
      In the present study, we investigated this relationship more closely by examining
      whether imposed changes in stride length could affect head excursions during head
      bobbing. We manipulated stride length by hobbling chicks immediately after
      hatching and subsequently quantified kinematic parameters, including step timing
      and head excursions, during walking. Imposition of shorter stride lengths induced
      chicks to take more frequent steps, spend less time in contact with the ground,
      and shortened head excursions during head bobbing. Nevertheless, the
      developmental changes in head excursions were not fully accounted for by altered
      stride lengths, so in a separate experiment, we investigated whether the
      development of head bobbing relies on the normal experience of optic flow. We
      raised chicks under stroboscopic illumination to eliminate chicks' experience of
      optic flow but found that this did not significantly alter head bobbing. These
      results are discussed along with related findings in other species and the
      possible neural and biomechanical constraints underlying development of walking
      and head bobbing in birds.

PMID- 16093328
TI  - Heat shock-mediated thermoprotection of larval locomotion compromised by
      ubiquitous overexpression of Hsp70 in Drosophila melanogaster.
AB  - Maintaining the competence of locomotor circuitry under stressful conditions can
      benefit organisms by enabling locomotion to more tolerable microhabitats. We show
      that prior heat shock protects locomotion and the locomotor central pattern
      generator of larval Drosophila against subsequent hyperthermic stress. We
      combined molecular genetic, electrophysiological, and behavioral techniques to
      investigate heat shock-mediated thermoprotection. Prior heat shock increased the
      distance traveled by larvae during hyperthermia before failure. The frequency of
      the rhythm of peristaltic locomotor contractions and the velocity of locomotion
      were both less thermosensitive after heat shock and were less susceptible to
      failure at high temperatures. Rhythmic coordinated motor patterns, recorded
      intracellularly as excitatory junction potentials in body wall muscles of
      dissected preparations, were centrally generated because patterns could still be
      generated in the absence of sensory feedback (sensory function disrupted with
      shibire). Prior heat shock protected central circuit operation during
      hyperthermic stress by increasing the temperature at which it failed.
      Overexpression of Hsp70 after a heat shock using transgenic flies (traII) did not
      enhance thermoprotection, as expected, but had deleterious effects on parameters
      of behavior.

PMID- 16093329
TI  - Development of GLAST(+) astrocytes and NG2(+) glia in rat hippocampus CA1: mature
      astrocytes are electrophysiologically passive.
AB  - Glia show marked heterogeneity in terms of electrophysiology in the developing
      brain, and two major types can be identified based on GFAP or NG2 expression.
      However, it remains to be determined if such an electrophysiological diversity
      holds for the adult brain and how GFAP and NG2 lineage glia are associated with
      different electrophysiological phenotypes during the course of development. To
      address these fundamental questions, we performed in situ whole cell recording
      from morphologically identified glia from the rat hippocampal CA1 region from
      postnatal (P) days 1-106 and double-stained postrecorded cells with GLAST and NG2
      antibodies. We found glia express mostly voltage-gated outward K(+) currents and
      also have inward Na(+) currents in the newborn (P1-P3), but these are no longer
      present after P22. They consist equally of GLAST(+) and NG2(+) cells in the
      newborn, but are mainly NG2(+) in juvenile animals (P4-P21). Glia showing voltage
      gated outward and inward K(+) currents are also present at P1, peak at P5 and
      decline to a stationary level of approximately 10% in the adult. They are
      GLAST(+) astrocytes from newborn to juvenile but NG2(+) glia in the adult.
      Electrophysiologically passive glia first appear at P4 and increase to 91% in
      adults, of which 85% are GLAST(+). These results indicate that glial
      electrophysiological diversity occurs predominantly in the developing brain.
      While most glia in the NG2 lineage preserve a certain amount of voltage-gated ion
      conductances, mature GLAST(+) astrocytes are electrophysiologically passive.

PMID- 16093330
TI  - Whisker trimming begun at birth or on postnatal day 12 affects excitatory and
      inhibitory receptive fields of layer IV barrel neurons.
AB  - In rats, whisker trimming during development leads to persistent alterations in
      the function of cortical barrel circuits and to behavioral deficits later in
      life. Here we examined how whisker trimming begun either at birth (P0) or on
      postnatal day 12 (P12), around the onset of whisking behavior, affects receptive
      fields of layer IV barrel neurons. All whiskers on the left face were trimmed for
      40-45 days and then allowed to regrow fully. Extracellular single-unit recordings
      and controlled deflections of principal and adjacent whiskers (PW and AW,
      respectively), individually or in paired combinations, were used to assess
      excitatory and suppressive effects of neighboring whiskers on barrel neurons.
      Results indicate that whisker trimming both from P0 and P12 leads to enlarged
      excitatory and weakened inhibitory receptive fields in layer IV neurons. PW- and
      AW-evoked responses are larger in magnitude in trimmed than in control animals;
      AW-evoked responses are disproportionately affected, decreasing the spatial focus
      of barrel neurons. Deprivation after P12 accounts for approximately 50% of the
      total effect observed in P0 trimmed animals. Suppressive interactions, evoked by
      two whiskers deflected in succession, are weaker in trimmed than in control
      animals. Suppressive caudal/rostral and ventral/dorsal gradients, however, seem
      unaffected by sensory deprivation. Thus the developmental period during which
      experience persistently modifies maturing barrel circuitry extends up to and
      likely beyond the onset of whisking behavior. Sensory deprivation during this
      time affects development of both excitatory and inhibitory receptive fields of
      barrel neurons and likely impairs cortical integration of sensory information
      from multiple whiskers.

PMID- 16093331
TI  - A role for hip position in initiating the swing-to-stance transition in walking
      cats.
AB  - In this investigation, we obtained data that support the hypothesis that afferent
      signals associated with hip flexion play a role in initiating the swing-to-stance
      transition of the hind legs in walking cats. Direct evidence came from
      observations in walking decerebrate cats. Assisting the flexion of the hip joint
      during swing advanced the onset of activity in ankle extensor muscles, and this
      advance was strongly correlated with a reduction in the duration of hip flexor
      muscle activity. The hip angle at the time of onset of the flexion to extension
      transition was similar during assisted and unassisted steps. Additional evidence
      for the hypothesis that sensory signals related to hip flexion are important in
      regulating the swing-to-stance transition came from four normal animals trained
      to walk in a variety of situations designed to alter the coordination of
      movements at the hip, knee, and ankle joints during the swing phase. Although
      there were exceptions in some tasks and preparations, the angle of the hip joint
      at the time of onset of extensor activity was generally less variable than that
      of the knee and ankle joints. We also found no clear relationships between the
      angle of the limb and body axes, or the length of the limb axis, and the time of
      onset of extensor activity. Finally, there were no indications that the
      stretching of ankle extensor muscles during swing was a factor in regulating the
      transition from swing-to-stance.

PMID- 16093332
TI  - Contributions of intrinsic membrane dynamics to fast network oscillations with
      irregular neuronal discharges.
AB  - During fast oscillations in the local field potential (40-100 Hz gamma, 100-200
      Hz sharp-wave ripples) single cortical neurons typically fire irregularly at
      rates that are much lower than the oscillation frequency. Recent computational
      studies have provided a mathematical description of such fast oscillations, using
      the leaky integrate-and-fire (LIF) neuron model. Here, we extend this theoretical
      framework to populations of more realistic Hodgkin-Huxley-type conductance-based
      neurons. In a noisy network of GABAergic neurons that are connected randomly and
      sparsely by chemical synapses, coherent oscillations emerge with a frequency that
      depends sensitively on the single cell's membrane dynamics. The population
      frequency can be predicted analytically from the synaptic time constants and the
      preferred phase of discharge during the oscillatory cycle of a single cell
      subjected to noisy sinusoidal input. The latter depends significantly on the
      single cell's membrane properties and can be understood in the context of the
      simplified exponential integrate-and-fire (EIF) neuron. We find that 200-Hz
      oscillations can be generated, provided the effective input conductance of single
      cells is large, so that the single neuron's phase shift is sufficiently small. In
      a two-population network of excitatory pyramidal cells and inhibitory neurons,
      recurrent excitation can either decrease or increase the population rhythmic
      frequency, depending on whether in a neuron the excitatory synaptic current
      follows or precedes the inhibitory synaptic current in an oscillatory cycle.
      Detailed single-cell properties have a substantial impact on population
      oscillations, even though rhythmicity does not originate from pacemaker neurons
      and is an emergent network phenomenon.

PMID- 16093333
TI  - Sensory neurons from Nf1 haploinsufficient mice exhibit increased excitability.
AB  - Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by
      tumor formation. People with NF1 also can experience more intense painful
      responses to stimuli, such as minor trauma, than normal. NF1 results from a
      heterozygous mutation of the NF1 gene, leading to decreased levels of
      neurofibromin, the protein product of the NF1 gene. Neurofibromin is a guanosine
      triphosphatase activating protein (GAP) for Ras and accelerates the conversion of
      active Ras-GTP to inactive Ras-GDP; therefore mutation of the NF1 gene frequently
      results in an increase in activity of the Ras transduction cascade. Using patch
      clamp electrophysiological techniques, we examined the excitability of capsaicin
      sensitive sensory neurons isolated from the dorsal root ganglia of adult mice
      with a heterozygous mutation of the Nf1 gene (Nf1+/-), analogous to the human
      mutation, in comparison to wildtype sensory neurons. Sensory neurons from adult
      Nf1+/- mice generated a more than twofold higher number of action potentials in
      response to a ramp of depolarizing current as wild-type neurons. Consistent with
      the greater number of action potentials, Nf1+/- neurons had lower firing
      thresholds, lower rheobase currents, and shorter firing latencies than wild-type
      neurons. Interestingly, nerve growth factor augmented the excitability of wild
      type neurons in a concentration-related manner but did not further alter the
      excitability of the Nf1+/- sensory neurons. These data clearly suggest that GAPs,
      such as neurofibromin, can play a key role in the excitability of nociceptive
      sensory neurons. This increased excitability may explain the painful conditions
      experienced by people with NF1.

PMID- 16093334
TI  - Regulation of IPSP theta rhythm by muscarinic receptors and endocannabinoids in
      hippocampus.
AB  - Theta rhythms are behaviorally relevant electrical oscillations in the mammalian
      brain, particularly the hippocampus. In many cases, theta oscillations are shaped
      by inhibitory postsynaptic potentials (IPSPs) that are driven by glutamatergic
      and/or cholinergic inputs. Here we show that hippocampal theta rhythm IPSPs
      induced in the CA1 region by muscarinic acetylcholine receptors independent of
      all glutamate receptors can be briefly interrupted by action potential-induced,
      retrograde endocannabinoid release. Theta IPSPs can be recorded in CA1 pyramidal
      cell somata surgically isolated from CA3, subiculum, and even from their own
      apical dendrites. These results suggest that perisomatic-targeting interneurons
      whose output is subject to inhibition by endocannabinoids are the likely source
      of theta IPSPs. Interneurons having these properties include the cholecystokinin
      containing cells. Simultaneous recordings from pyramidal cell pairs reveal
      synchronous theta-frequency IPSPs in neighboring pyramidal cells, suggesting that
      these IPSPs may help entrain or modulate small groups of pyramidal cells.

PMID- 16093335
TI  - Adenosine down-regulates giant depolarizing potentials in the developing rat
      hippocampus by exerting a negative control on glutamatergic inputs.
AB  - Adenosine is a widespread neuromodulator that can be directly released in the
      extracellular space during sustained network activity or can be generated as the
      breakdown product of adenosine triphosphate (ATP). Whole cell patch-clamp
      recordings were performed from CA3 principal cells and interneurons in
      hippocampal slices obtained from P2-P7 neonatal rats to study the modulatory
      effects of adenosine on giant depolarizing potentials (GDPs) that constitute the
      hallmark of developmental networks. We found that GDPs were extremely sensitive
      to the inhibitory action of adenosine (IC(50) = 0.52 microM). Adenosine also
      contributed to the depressant effect of ATP as indicated by DPCPX-sensitive
      changes of ATP-induced reduction of GDP frequency. Similarly, adenosine exerted a
      strong inhibitory action on spontaneous glutamatergic synaptic events recorded
      from GABAergic interneurons and on interictal bursts that developed in CA3
      principal cells after blockade of gamma-aminobutyric acid type A (GABA(A))
      receptors with bicuculline. All these effects were prevented by DPCPX, indicating
      the involvement of inhibitory A1 receptors. In contrast, GABAergic synaptic
      events were not changed by adenosine. Consistent with the endogenous role of
      adenosine on network activity, DPCPX per se increased the frequency of GDPs,
      interictal bursts, and spontaneous glutamatergic synaptic events recorded from
      GABAergic interneurons. Moreover, the adenosine transport inhibitor NBTI and the
      adenosine deaminase blocker EHNA decreased the frequency of GDPs, thus providing
      further evidence that endogenous adenosine exerts a powerful control on GDP
      generation. We conclude that, in the neonatal rat hippocampus, the inhibitory
      action of adenosine on GDPs arises from the negative control of glutamatergic,
      but not GABAergic, inputs.

PMID- 16093336
TI  - Environmental enrichment increases paired-pulse depression in rat auditory
      cortex.
AB  - Temporal features are important for the identification of natural sounds. Earlier
      studies have shown that cortical processing of temporal information can be
      altered by long-term experience with modulated sounds. In a previous study, we
      observed that environmental enrichment dramatically increased the response of
      cortical neurons to single tone and noise burst stimuli in both awake and
      anesthetized rats. Here, we evaluate how enrichment influences temporal
      information processing in the auditory cortex. We recorded responses to repeated
      tones and noise bursts in awake rats using epidural evoked potentials and in
      anesthetized rats using microelectrodes. Enrichment increased the response of
      cortical neurons to stimuli presented at slow rates and decreased the response to
      stimuli presented at fast rates relative to controls. Our observation that
      enrichment substantially increased response strength and forward masking is
      consistent with earlier reports that long-term potentiation of cortical synapses
      is associated with increased paired-pulse depression. Enrichment also increased
      response synchronization at slow rates and decreased synchronization at fast
      rates. Paired-pulse depression increased within days of environmental enrichment
      and was restored to normal levels after return to standard housing conditions.
      These results are relevant to several clinical disorders characterized by
      abnormal gating of sensory information, including autism, schizophrenia, and
      dyslexia.

PMID- 16093338
TI  - Constraining compartmental models using multiple voltage recordings and genetic
      algorithms.
AB  - Compartmental models with many nonlinearly and nonhomogeneous distributions of
      voltage-gated conductances are routinely used to investigate the physiology of
      complex neurons. However, the number of loosely constrained parameters makes
      manually constructing the desired model a daunting if not impossible task.
      Recently, progress has been made using automated parameter search methods, such
      as genetic algorithms (GAs). However, these methods have been applied to
      somatically recorded action potentials using relatively simple target functions.
      Using a genetic minimization algorithm and a reduced compartmental model based on
      a previously published model of layer 5 neocortical pyramidal neurons we compared
      the efficacy of five cost functions (based on the waveform of the membrane
      potential, the interspike interval, trajectory density, and their combinations)
      to constrain the model. When the model was constrained using somatic recordings
      only, a combined cost function was found to be the most effective. This combined
      cost function was then applied to investigate the contribution of dendritic and
      axonal recordings to the ability of the GA to constrain the model. The more
      recording locations from the dendrite and the axon that were added to the data
      set the better was the genetic minimization algorithm able to constrain the
      compartmental model. Based on these simulations we propose an experimental scheme
      that, in combination with a genetic minimization algorithm, may be used to
      constrain compartmental models of neurons.

PMID- 16093337
TI  - Optical recording of fast neuronal membrane potential transients in acute
      mammalian brain slices by second-harmonic generation microscopy.
AB  - Although nonlinear microscopy and fast (approximately 1 ms) membrane potential
      (Vm) recording have proven valuable for neuroscience applications, their
      potentially powerful combination has not yet been shown for studies of Vm
      activity deep in intact tissue. We show that laser illumination of neurons in
      acute rat brain slices intracellularly filled with FM4-64 dye generates an
      intense second-harmonic generation (SHG) signal from somatic and dendritic plasma
      membranes with high contrast >125 microm below the slice surface. The SHG signal
      provides a linear response to DeltaVm of approximately 7.5%/100 mV. By averaging
      repeated line scans (approximately 50), we show the ability to record action
      potentials (APs) optically with a signal-to-noise ratio (S/N) of approximately 7
      8. We also show recording of fast Vm steps from the dendritic arbor at depths
      inaccessible with previous methods. The high membrane contrast and linear
      response of SHG to DeltaVm provides the advantage that signal changes are not
      degraded by background and can be directly quantified in terms of DeltaVm.
      Experimental comparison of SHG and two-photon fluorescence Vm recording with the
      best known probes for each showed that the SHG technique is superior for Vm
      recording in brain slice applications, with FM4-64 as the best tested SHG Vm
      probe.

PMID- 16093339
TI  - Responses of ventral cochlear nucleus neurons to contralateral sound after
      conductive hearing loss.
AB  - Conductive hearing loss (CHL) is an attenuation of signals stimulating the
      cochlea, without damage to the auditory end organ. It can cause central auditory
      processing deficits that outlast the CHL itself. Measures of oxidative metabolism
      show a decrease in activity of nuclei receiving input originating at the affected
      ear but, surprisingly, an increase in the activity of second-order neurons of the
      opposite ear. In normal hearing animals, contralateral sound produces an
      inhibitory response to broadband noise in approximately one third of ventral
      cochlear nucleus (VCN) neurons. Excitatory responses also occur but are very
      rare. We looked for changes in the binaural properties of neurons in the VCN of
      guinea pigs at intervals immediately, 1 day, 1 wk, and 2 wk after the induction
      of a unilateral CHL by ossicular disruption. CHL was always induced in the ear
      ipsilateral to the VCN from which recordings were made. The main observations
      were as follows: 1) ipsilateral excitatory thresholds were raised by at least 40
      dB; 2) contralateral inhibitory responses showed a small but statistically
      significant immediate decrease followed by an increase, returning to normal by 14
      days; and 3) there was a large increase in the proportion of units with
      excitatory responses to contralateral BBN. The increase was immediate and
      lasting. The latencies of the excitatory responses were at least 6 ms, consistent
      with activation by a path involving several synapses and inconsistent with cross
      talk. The latencies and rate-level functions of contralateral excitation were
      similar to those seen occasionally in normal hearing animals, suggesting an
      upregulation of an existing pathway. In conclusion, contralateral excitatory
      inputs to the VCN exist, which are not normally effective, and can compensate
      rapidly for large changes in afferent input.

PMID- 16093340
TI  - Suppression of ih contributes to propofol-induced inhibition of mouse cortical
      pyramidal neurons.
AB  - The contributions of the hyperpolarization-activated current, I(h), to generation
      of rhythmic activities are well described for various central neurons,
      particularly in thalamocortical circuits. In the present study, we investigated
      effects of a general anesthetic, propofol, on native I(h) in neurons of thalamus
      and cortex and on the corresponding cloned HCN channel subunits. Whole cell
      voltage-clamp recordings from mouse brain slices identified neuronal I(h)
      currents with fast activation kinetics in neocortical pyramidal neurons and with
      slower kinetics in thalamocortical relay cells. Propofol inhibited the fast
      activating I(h) in cortical neurons at a clinically relevant concentration (5
      microM); inhibition of I(h) involved a hyperpolarizing shift in half-activation
      voltage (DeltaV1/2 approximately -9 mV) and a decrease in maximal available
      current (approximately 36% inhibition, measured at -120 mV). With the slower form
      of I(h) expressed in thalamocortical neurons, propofol had no effect on current
      activation or amplitude. In heterologous expression systems, 5 muM propofol
      caused a large shift in V1/2 and decrease in current amplitude in homomeric HCN1
      and linked heteromeric HCN1-HCN2 channels, both of which activate with fast
      kinetics but did not affect V1/2 or current amplitude of slowly activating
      homomeric HCN2 channels. With GABA(A) and glycine receptor channels blocked,
      propofol caused membrane hyperpolarization and suppressed action potential
      discharge in cortical neurons; these effects were occluded by the I(h) blocker,
      ZD-7288. In summary, these data indicate that propofol selectively inhibits HCN
      channels containing HCN1 subunits, such as those that mediate I(h) in cortical
      pyramidal neurons-and they suggest that anesthetic actions of propofol may
      involve inhibition of cortical neurons and perhaps other HCN1-expressing cells.

PMID- 16093341
TI  - Cholecystokinin octapeptide increases spontaneous glutamatergic synaptic
      transmission to neurons of the nucleus tractus solitarius centralis.
AB  - Cholecystokinin (CCK) is released from enteroendocrine cells after ingestion of
      nutrients and induces multiple effects along the gastrointestinal tract,
      including gastric relaxation and short-term satiety. We used whole cell patch
      clamp and immunohistochemical techniques in rat brain stem slices to characterize
      the effects of CCK. In 45% of the neurons of nucleus tractus solitarius
      subnucleus centralis (cNTS), perfusion with the sulfated form of CCK (CCK-8s)
      increased the frequency of spontaneous excitatory currents (sEPSCs) in a
      concentration-dependent manner (1-300 nM). The threshold for the CCK-8s
      excitatory effect was 1 nM, the EC(50) was 20 nM, and E(max) was 100 nM. The
      excitatory effects of CCK-8s were still present when the slices were preincubated
      with tetrodotoxin or bicuculline or when the recordings were conducted with Cs(+)
      electrodes. Pretreatment with the CCK-A receptor antagonist, lorglumide (1
      microM), antagonized the effects of CCK-8s, whereas perfusion with the CCK-B
      preferring agonist CCK-8 nonsulfated (CCK-ns, 1 microM) did not affect the
      frequency of sEPSCs. Similarly, pretreatment with the CCK-B receptor antagonist,
      triglumide (1 microM), did not prevent the actions of CCK-8s. Although the
      majority (i.e., 76%) of CCK-8s unresponsive cNTS neurons had a bipolar somata
      shape and were TH-IR negative, no differences were found in either the
      morphological or the neurochemical phenotype of cNTS neurons responsive to CCK
      8s. Our results suggest that the excitatory effects of CCK-8s on terminals
      impinging on a subpopulation of cNTS neurons are mediated by CCK-A receptors;
      these responsive neurons, however, do not have morphological or neurochemical
      characteristics that automatically distinguish them from nonresponsive neurons.

PMID- 16093342
TI  - Myomodulin increases Ih and inhibits the NA/K pump to modulate bursting in leech
      heart interneurons.
AB  - In the medicinal leech, a rhythmically active 14-interneuron network composes the
      central pattern generator for heartbeat. In two segmental ganglia, bilateral
      pairs of reciprocally inhibitory heart interneurons (oscillator interneurons)
      produce a rhythm of alternating bursts of action potentials that paces activity
      in the pattern-generating network. The neuropeptide myomodulin decreases the
      period of this bursting and increases the intraburst spike frequency when applied
      to isolated ganglia containing these oscillator interneurons. Myomodulin also
      decreases period, increases spike frequency, and increases the robustness of
      endogenous bursting in synaptically isolated (with bicuculline) oscillator
      interneurons. In voltage-clamp experiments using hyperpolarizing ramps, we
      identify an increase in membrane conductance elicited by myomodulin with the
      properties of a hyperpolarization-activated current. Voltage steps confirm that
      myomodulin indeed increases the maximum conductance of the hyperpolarization
      activated current I(h). In similar experiments using Cs(+) to block I(h), we
      demonstrate that myomodulin also causes a steady offset in the ramp current that
      is not associated with an increase in conductance. This current offset is blocked
      by ouabain, indicating that myomodulin inhibits the Na/K pump. In current-clamp
      experiments, when I(h) is blocked with Cs(+), myomodulin decreases period and
      increases spike frequency of alternating bursting in synaptically connected
      oscillator interneurons, suggesting that inhibiting the Na/K pump modulates these
      burst characteristics. These observations indicate that myomodulin decreases
      period and increases spike frequency of endogenous bursting in synaptically
      isolated oscillator heart interneurons and alternating bursting of reciprocally
      inhibitory pairs of interneurons, at least in part, by increasing I(h) and by
      decreasing the Na/K pump.

PMID- 16093343
TI  - High gamma activity in response to deviant auditory stimuli recorded directly
      from human cortex.
AB  - We recorded electrophysiological responses from the left frontal and temporal
      cortex of awake neurosurgical patients to both repetitive background and rare
      deviant auditory stimuli. Prominent sensory event-related potentials (ERPs) were
      recorded from auditory association cortex of the temporal lobe and adjacent
      regions surrounding the posterior Sylvian fissure. Deviant stimuli generated an
      additional longer latency mismatch response, maximal at more anterior temporal
      lobe sites. We found low gamma (30-60 Hz) in auditory association cortex, and we
      also show the existence of high-frequency oscillations above the traditional
      gamma range (high gamma, 60-250 Hz). Sensory and mismatch potentials were not
      reliably observed at frontal recording sites. We suggest that the high gamma
      oscillations are sensory-induced neocortical ripples, similar in physiological
      origin to the well-studied ripples of the hippocampus.

PMID- 16093344
TI  - Differential processing of noxious colonic input by thoracolumbar and lumbosacral
      dorsal horn neurons in the rat.
AB  - Previous studies suggest the lumbosacral (LS) spinal cord processes acute
      colorectal stimuli whereas the thoracolumbar (TL) and LS spinal segments process
      inflammatory stimuli. In this study, the effects of colorectal distention (CRD)
      on TL and LS dorsal horn neuronal activity were recorded in Nembutal-anesthetized
      male rats both with and without colonic inflammation. Both single cells (before
      and after inflammation) and populations (multiple cells from noninflamed or
      inflamed rats) were studied. CRD-responsive neurons had excitatory Abrupt (on-off
      with stimulus) or Sustained (prolonged after discharge) responses or were
      Inhibited by CRD. In noninflamed rats, a significantly greater percentage of LS
      neurons (63% Abrupt, 27% Sustained) were excited by CRD than TL neurons (61%
      Abrupt, 3% Sustained). The remaining cells were Inhibited (10% LS, 36% TL). LS
      Abrupt neurons had lower thresholds and greater response magnitudes to CRD
      compared with TL Abrupt neurons. After colonic inflammation, TL neurons became
      more excitable: the percentage of Inhibited neurons decreased, the response
      magnitude of Abrupt neurons increased, and the threshold decreased. In contrast,
      in single-cell recordings, the response of LS Sustained neurons increased,
      whereas LS Abrupt neurons decreased. These data suggest that in noninflamed rats,
      the net response to CRD of TL visceroceptive spinal sensory neurons is less than
      that of LS neurons. Colonic inflammation increases the net response of TL neurons
      and differentially modulates the response of LS neurons. These differences may
      contribute to the functional dichotomy between the TL and LS spinal segments in
      processing acute and inflammatory colorectal pain.

PMID- 16093345
TI  - ODA16p, a Chlamydomonas flagellar protein needed for dynein assembly.
AB  - Dynein motors of cilia and flagella function in the context of the axoneme, a
      very large network of microtubules and associated proteins. To understand how
      dyneins assemble and attach to this network, we characterized two Chlamydomonas
      outer arm dynein assembly (oda) mutants at a new locus, ODA16. Both oda16 mutants
      display a reduced beat frequency and altered swimming behavior, similar to
      previously characterized oda mutants, but only a partial loss of axonemal dyneins
      as shown by both electron microscopy and immunoblots. Motility studies suggest
      that the remaining outer arm dyneins on oda16 axonemes are functional. The ODA16
      locus encodes a 49-kDa WD-repeat domain protein. Homologues were found in
      mammalian and fly databases, but not in yeast or nematode databases, implying
      that this protein is only needed in organisms with motile cilia or flagella. The
      Chlamydomonas ODA16 protein shares 62% identity with its human homologue. Western
      blot analysis localizes more than 90% of ODA16p to the flagellar matrix. Because
      wild-type axonemes retain little ODA16p but can be reactivated to a normal beat
      in vitro, we hypothesize that ODA16p is not an essential dynein subunit, but a
      protein necessary for dynein transport into the flagellar compartment or assembly
      onto the axoneme.

PMID- 16093346
TI  - Oligomerization and dissociation of AP-1 adaptors are regulated by cargo signals
      and by ArfGAP1-induced GTP hydrolysis.
AB  - The mechanism of AP-1/clathrin coat formation was analyzed using purified adaptor
      proteins and synthetic liposomes presenting tyrosine sorting signals. AP-1
      adaptors recruited in the presence of Arf1.GTP and sorting signals were found to
      oligomerize to high-molecular-weight complexes even in the absence of clathrin.
      The appendage domains of the AP-1 adaptins were not required for oligomerization.
      On GTP hydrolysis induced by the GTPase-activating protein ArfGAP1, the complexes
      were disassembled and AP-1 dissociated from the membrane. AP-1 stimulated ArfGAP1
      activity, suggesting a role of AP-1 in the regulation of the Arf1 "GTPase timer."
      In the presence of cytosol, AP-1 could be recruited to liposomes without sorting
      signals, consistent with the existence of docking factors in the cytosol. Under
      these conditions, however, AP-1 remained monomeric, and recruitment in the
      presence of GTP was short-lived. Sorting signals allowed stable recruitment and
      oligomerization also in the presence of cytosol. These results suggest a
      mechanism whereby initial assembly of AP-1 with Arf1.GTP and ArfGAP1 on the
      membrane stimulates Arf1 GTPase activity, whereas interaction with cargo induces
      oligomerization and reduces the rate of GTP hydrolysis, thus contributing to
      efficient cargo sorting.

PMID- 16093347
TI  - A novel degron-mediated degradation of the RTG pathway regulator, Mks1p, by
      SCFGrr1.
AB  - Yeast cells respond to mitochondrial dysfunction by altering the expression of a
      subset of nuclear genes, a process known as retrograde signaling (RS). RS
      terminates with two transcription factors, Rtg1p and Rtg3p. One positive
      regulator, Rtg2p, and four negative regulators, Lst8p, Mks1p, and the redundant
      14-3-3 proteins, Bmh1p and Bmh2p, control RS upstream of Rtg1/3p. Mks1p is
      negatively regulated by binding to Rtg2p and positively regulated when bound to
      Bmh1/2p. Here we report that Grr1p, a component of the SCF(Grr1) E3 ubiquitin
      ligase, modulates RS by affecting Mks1p levels. Grr1p polyubiquitinates Mks1p not
      bound to either Rtg2p or to Bmh1/2p, targeting it for degradation. An acidic
      domain region of Mks1p constitutes the portable Mks1p degron sequence. We have
      isolated dominant mutations in Grr1p leading to increased Mks1p degradation.
      These mutations result in a gain of positive charge on the concave surface of the
      leucine rich repeat (LRR) domain of Grr1p, the proposed substrate binding site.
      We propose that Mks1p is a central player of RS and is acted upon by multiple
      regulators of the pathway.

PMID- 16093348
TI  - CDK phosphorylation of a novel NLS-NES module distributed between two subunits of
      the Mcm2-7 complex prevents chromosomal rereplication.
AB  - Cyclin-dependent kinases (CDKs) use multiple mechanisms to block reassembly of
      prereplicative complexes (pre-RCs) at replication origins to prevent
      inappropriate rereplication. In Saccharomyces cerevisiae, one of these mechanisms
      promotes the net nuclear export of a pre-RC component, the Mcm2-7 complex, during
      S, G2, and M phases. Here we identify two partial nuclear localization signals
      (NLSs) on Mcm2 and Mcm3 that are each necessary, but not sufficient, for nuclear
      localization of the Mcm2-7 complex. When brought together in cis, however, the
      two partial signals constitute a potent NLS, sufficient for robust nuclear
      localization when fused to an otherwise cytoplasmic protein. We also identify a
      Crm1-dependent nuclear export signal (NES) adjacent to the Mcm3 NLS. Remarkably,
      the Mcm2-Mcm3 NLS and the Mcm3 NES are sufficient to form a transport module that
      recapitulates the cell cycle-regulated localization of the entire Mcm2-7 complex.
      Moreover, we show that CDK regulation promotes net export by phosphorylation of
      the Mcm3 portion of this module and that nuclear export of the Mcm2-7 complex is
      sufficient to disrupt replication initiation. We speculate that the distribution
      of partial transport signals among distinct subunits of a complex may enhance the
      specificity of protein localization and raises the possibility that previously
      undetected distributed transport signals are used by other multiprotein
      complexes.

PMID- 16093349
TI  - Dual interaction of JAM-C with JAM-B and alpha(M)beta2 integrin: function in
      junctional complexes and leukocyte adhesion.
AB  - The junctional adhesion molecules (JAMs) have been recently described as
      interendothelial junctional molecules and as integrin ligands. Here we show that
      JAM-B and JAM-C undergo heterophilic interaction in cell-cell contacts and that
      JAM-C is recruited and stabilized in junctional complexes by JAM-B. In addition,
      soluble JAM-B dissociates soluble JAM-C homodimers to form JAM-B/JAM-C
      heterodimers. This suggests that the affinity of JAM-C monomers to form dimers is
      higher for JAM-B than for JAM-C. Using antibodies against JAM-C, the formation of
      JAM-B/JAM-C heterodimers can be abolished. This liberates JAM-C from its vascular
      binding partner JAM-B and makes it available on the apical side of vessels for
      interaction with its leukocyte counter-receptor alpha(M)beta2 integrin. We
      demonstrate that the modulation of JAM-C localization in junctional complexes is
      a new regulatory mechanism for alpha(M)beta2-dependent adhesion of leukocytes.

PMID- 16093350
TI  - Synaptotagmin isoforms couple distinct ranges of Ca2+, Ba2+, and Sr2+
      concentration to SNARE-mediated membrane fusion.
AB  - Ca2+-triggered exocytosis of synaptic vesicles is controlled by the Ca2+-binding
      protein synaptotagmin (syt) I. Fifteen additional isoforms of syt have been
      identified. Here, we compared the abilities of three syt isoforms (I, VII, and
      IX) to regulate soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor (SNARE)-mediated membrane fusion in vitro in response to divalent
      cations. We found that different isoforms of syt couple distinct ranges of Ca2+,
      Ba2+, and Sr2+ to membrane fusion; syt VII was approximately 400-fold more
      sensitive to Ca2+ than was syt I. Omission of phosphatidylserine (PS) from both
      populations of liposomes completely abrogated the ability of all three isoforms
      of syt to stimulate fusion. Mutations that selectively inhibit syt.target-SNARE
      (t-SNARE) interactions reduced syt stimulation of fusion. Using Sr2+ and Ba2+, we
      found that binding of syt to PS and t-SNAREs can be dissociated from activation
      of fusion, uncovering posteffector-binding functions for syt. Our data
      demonstrate that different syt isoforms are specialized to sense different ranges
      of divalent cations and that PS is an essential effector of Ca2+.syt action.

PMID- 16093351
TI  - Mammalian septins regulate microtubule stability through interaction with the
      microtubule-binding protein MAP4.
AB  - Mammalian septins constitute a family of at least 12 GTP-binding proteins that
      can form hetero-oligomers and that are sometimes found in association with actin
      or microtubule filaments. However, their functions are not understood. Using RNA
      interference, we found that suppression of septin expression in HeLa cells caused
      a pronounced increase in microtubule stability. Mass spectroscopic analysis of
      proteins coprecipitating with Sept6 identified the microtubule-associated protein
      MAP4 as a septin binding partner. A small, proline-rich region in the C-terminal
      half of MAP4 bound directly to a Sept 2:6:7 heterotrimer, and to the Sept2
      monomer. The trimer blocked the ability of this MAP4 fragment to bind and bundle
      microtubules in vitro. In intact cells, MAP4 was required for the stabilization
      of microtubules induced by septin depletion. Moreover, septin depletion increased
      the number of cells with abnormal nuclei, and this effect was blocked by gene
      silencing of MAP4. These data identify a novel molecular function for septins in
      mammalian cells: the modulation of microtubule dynamics through interaction with
      MAP4.

PMID- 16093353
TI  - Control of Golgi morphology and function by Sed5 t-SNARE phosphorylation.
AB  - Previously, we demonstrated that the phosphorylation of t-SNAREs by protein
      kinase A (PKA) affects their ability to participate in SNARE complexes and to
      confer endocytosis and exocytosis in yeast. Here, we show that the presumed
      phosphorylation of a conserved membrane-proximal PKA consensus site (serine-317)
      in the Sed5 t-SNARE regulates endoplasmic reticulum (ER)-Golgi transport, as well
      as Golgi morphology. Sed5 is a phosphoprotein, and both alanine and aspartate
      substitutions in serine-317 directly affect intracellular protein trafficking.
      The aspartate substitution results in elaboration of the ER, defects in Golgi-ER
      retrograde transport, an accumulation of small transport vesicles, and the
      inhibition of growth of most cell types. In contrast, the alanine substitution
      has no deleterious effects upon transport and growth, but results in ordering of
      the Golgi into a structure reminiscent of mammalian apparatus. This structure
      seems to require the recycling of Sed5, because it was found not to occur in
      sec21-2 cells that are defective in retrograde transport. Thus, a cycle of Sed5
      phosphorylation and dephosphorylation is required for normal t-SNARE function and
      may choreograph Golgi ordering and dispersal.

PMID- 16093352
TI  - YB-1 coordinates vascular smooth muscle alpha-actin gene activation by
      transforming growth factor beta1 and thrombin during differentiation of human
      pulmonary myofibroblasts.
AB  - Profibrotic regulatory mechanisms for tissue repair after traumatic injury have
      developed under strong evolutionary pressure to rapidly stanch blood loss and
      close open wounds. We have examined the roles played by two profibrotic
      mediators, transforming growth factor beta1 (TGFbeta1) and thrombin, in directing
      expression of the vascular smooth muscle alpha-actin (SMalphaA) gene, an
      important determinant of myofibroblast differentiation and early protein marker
      for stromal cell response to tissue injury. TGFbeta1 is a well known
      transcriptional activator of the SMalphaA gene in myofibroblasts. In contrast,
      thrombin independently elevates SMalphaA expression in human pulmonary
      myofibroblasts at the posttranscriptional level. A common feature of SMalphaA up
      regulation mediated by thrombin and TGFbeta1 is the involvement of the cold shock
      domain protein YB-1, a potent repressor of SMalphaA gene transcription in human
      fibroblasts that also binds mRNA and regulates translational efficiency. YB-1
      dissociates from SMalphaA enhancer DNA in the presence of TGFbeta1 or its Smad 2,
      3, and 4 coregulatory mediators. Thrombin does not effect SMalphaA gene
      transcription but rather displaces YB-1 from SMalphaA exon 3 coding sequences
      previously shown to be required for mRNA translational silencing. The release of
      YB-1 from promoter DNA coupled with its ability to bind RNA and shuttle between
      the nucleus and cytoplasm is suggestive of a regulatory loop for coordinating
      SMalphaA gene output in human pulmonary myofibroblasts at both the
      transcriptional and translational levels. This loop may help restrict organ
      destructive remodeling due to excessive myofibroblast differentiation.

PMID- 16093355
TI  - The endogenous ratio of Smad2 and Smad3 influences the cytostatic function of
      Smad3.
AB  - Although Smad2 and Smad3, critical transcriptional mediators of transforming
      growth factor-beta (TGF-beta) signaling, are supposed to play a role in the TGF
      beta cytostatic program, it remains unclear whether TGF-beta delivers cytostatic
      signals through both Smads equally or through either differentially. Here, we
      report that TGF-beta cytostatic signals rely on a Smad3-, but not a Smad2-,
      dependent pathway and that the intensity of TGF-beta cytostatic signals can be
      modulated by changing the endogenous ratio of Smad3 to Smad2. Depleting
      endogenous Smad3 by RNA interference sufficiently interfered with TGF-beta
      cytostatic actions in various TGF-beta-sensitive cell lines, whereas raising the
      relative endogenous ratio of Smad3 to Smad2, by depleting Smad2, markedly
      enhanced TGF-beta cytostatic response. Consistently, Smad3 activation and its
      transcriptional activity upon TGF-beta stimulation were facilitated in Smad2
      depleted cells relative to controls. Most significantly, a single event of
      increasing this ratio by Smad2 depletion was sufficient to restore TGF-beta
      cytostatic action in cells resistant to TGF-beta. These findings suggest a new
      important determinant of sensitivity to TGF-beta cytostatic signaling.

PMID- 16093354
TI  - Identification of Raf-1 S471 as a novel phosphorylation site critical for Raf-1
      and B-Raf kinase activities and for MEK binding.
AB  - The Ras-Raf-MAPK cascade is a key growth-signaling pathway and its uncontrolled
      activation results in cell transformation. Although the general features of the
      signal transmission along the cascade are reasonably defined, the mechanisms
      underlying Raf activation remain incompletely understood. Here, we show that Raf
      1 dephosphorylation, primarily at epidermal growth factor (EGF)-induced sites,
      abolishes Raf-1 kinase activity. Using mass spectrometry, we identified five
      novel in vivo Raf-1 phosphorylation sites, one of which, S471, is located in
      subdomain VIB of Raf-1 kinase domain. Mutational analyses demonstrated that Raf-1
      S471 is critical for Raf-1 kinase activity and for its interaction with mitogen
      activated protein kinase kinase (MEK). Similarly, mutation of the corresponding B
      Raf site, S578, resulted in an inactive kinase, suggesting that the same Raf-1
      and B-Raf phosphorylation is needed for Raf kinase activation. Importantly, the
      naturally occurring, cancer-associated B-Raf activating mutation V599E suppressed
      the S578A mutation, suggesting that introducing a charged residue at this region
      eliminates the need for an activating phosphorylation. Our results demonstrate an
      essential role of specific EGF-induced Raf-1 phosphorylation sites in Raf-1
      activation, identify Raf-1 S471 as a novel phosphorylation site critical for Raf
      1 and B-Raf kinase activities, and point to the possibility that the V599E
      mutation activates B-Raf by mimicking a phosphorylation at the S578 site.

PMID- 16093357
TI  - Experimental intestinal endometriosis is characterized by increased levels of
      soluble TNFRSF1B and downregulation of Tnfrsf1a and Tnfrsf1b gene expression.
AB  - Endometriosis is commonly associated with symptoms similar to those of
      gastrointestinal diseases, such as inflammatory bowel disease (IBD), leading to
      erroneous diagnosis and inappropriate management. The role of tumor necrosis
      factor alpha (TNF) in IBD is well established, but its role in endometriosis-
      also characterized by the activation of inflammatory mechanisms--is still under
      study. Furthermore, little is known about the involvement of TNF receptors.
      Intestinal endometriosis was surgically induced in female Sprague-Dawley rats (n
      = 10). Control rats (n = 10) received sutures with no implants. Samples of tissue
      and fluids were collected 60 days after surgery. Endometriotic implants were
      classified in grades, and the gastrointestinal tract was examined for damage. A
      significant increase was observed in protein levels of TNF and soluble TNFRSF1B
      in the peritoneal fluid of experimental rats compared to controls. Expression of
      Tnf mRNA was significantly increased both in peritoneal leukocytes and in
      intestinal segments associated with implants in experimental animals. Bioactivity
      of TNF in tissues was confirmed by overexpression of Icam1, Sele, Vegfa, Flt1 and
      Kdr. Gene expression of Tnfrsf1a and Tnfrsf1b was downregulated in colon and
      small intestine of experimental animals, possibly as a mechanism of protection
      against TNF cytotoxicity. Significant overexpression of genes encoding TNF
      receptor-associated factors that have been linked to activation of antiapoptotic
      pathways also was observed. Overexpression of TNF and target genes,
      underexpression of TNF-receptor genes, and increased shedding of TNFRSF1B in this
      animal model provide further evidence for involvement of the TNF system in the
      pathogenesis of endometriosis.

PMID- 16093356
TI  - Effects of parathyroid hormone like hormone (PTHLH) antagonist, PTHLH(7-34), on
      fetoplacental development and growth during midgestation in rats.
AB  - Parathyroid hormone-like hormone (PTHLH) secretion has been reported in human
      amnion, chorion, decidual cytotrophoblast, syncytiotrophoblast, endometrium, and
      myometrium; however, the functions of PTHLH during pregnancy, particularly during
      placenta formation and fetal development, are not well understood. We examined
      whether neutralization of PTHLH action using PTHLH antagonist, PTHLH(7-34), in
      rats during early gestation affects fetal and placental growth. Rats received
      s.c. a daily dose of either 0, 4, 12, or 36 microg of PTHLH(7-34) infused
      continuously through mini-osmotic pumps from Day 8 through Day 15 of pregnancy.
      Fetal weights measured on Day 15 were significantly decreased in rats treated
      with all the doses of PTHLH(7-34) compared to controls, and decreases in
      placental weights were significant at the 12-microg dose. TUNEL assay
      demonstrated an increased number of apoptotic cells in placenta of treated rats,
      including rats treated with the 4-microg dose. Cleaved caspase 3 (CASP3), caspase
      9 (CASP9) (P < 0.05) and poly-ADP-ribose polymerase (PARP1) (P < 0.01) expression
      was increased and BCL2 (P < 0.01) expression was decreased in rats treated with 4
      microg PTHLH(7-34) compared to that in control. Placental cytochrome c expression
      was increased (P < 0.01) in cytosolic and decreased (P < 0.01) in mitochondrial
      fraction in PTHLH(7-34)-treated rats. Caspase 8 expression was not affected by
      the treatment. Immunohistochemical analysis of platelet endothelial cell adhesion
      molecule (PECAM1) showed higher staining intensity in control than in treated
      rats. In conclusion, these results suggests that PTHLH plays a role in early
      pregnancy, and that antagonization of PTHLH action causes fetoplacental growth
      restriction through activation of mitochondrial pathway of apoptosis in the
      placenta and through decreased expression of PECAM1.

PMID- 16093358
TI  - Impaired male sexual behavior in activin receptor type II knockout mice.
AB  - Integration of multiple hormonal and neuronal signaling pathways in the medial
      preoptic area (mPOA) is required for elicitation of male sexual behavior in most
      vertebrates. Perturbation of nitric oxide synthase (NOS) activity in the mPOA
      causes significant defects in male sexual behavior. Although activins and their
      signaling components are highly expressed throughout the brain, including the
      mPOA, their functional significance in the central nervous system (CNS) is
      unknown. Here, we demonstrate a neurophysiologic role for activin signaling in
      male reproductive behavior. Adult activin receptor type II null (Acvr2-/-) male
      mice display multiple reproductive behavioral deficits, including delayed
      initiation of copulation, reduced mount, and intromission frequencies, and
      increased mount, intromission, and ejaculation latencies. These behavioral
      defects in the adult mice are independent of gonadotropin-releasing hormone
      (GnRH) homeostasis or mating-induced changes in luteinizing hormone (LH) and
      testosterone levels. The impairment in behavior can be correlated to the nitric
      oxide content in the CNS because Acvr2-/- males have decreased NOS activity in
      the mPOA but not the rest of the hypothalamus or cortex. Olfactory acuity tests
      confirmed that Acvr2-/- mice have no defects in general odor or pheromone
      recognition. In addition, motor functions are not impaired and the mutants
      demonstrate normal neuromuscular coordination and balance. Furthermore, the
      penile histology in mutant mice appears normal, with no significant differences
      in the expression of penile differentiation marker genes compared with controls,
      suggesting the observed behavioral phenotypes are not due to structural defects
      in the penis. Our studies identify a previously unrecognized role of activin
      signaling in male sexual behavior and suggest that activins and/or related family
      members are upstream regulators of NOS activity within the mPOA of the forebrain.

PMID- 16093359
TI  - Immunological microenvironments in the human vagina and cervix: mediators of
      cellular immunity are concentrated in the cervical transformation zone.
AB  - Cell-mediated immunity (CMI) is key to defense against intracellular pathogens
      such as Chlamydia trachomatis and viruses that infect the lower female genital
      tract, but little is known about CMI at this site. Recent studies indicate that
      there are immunological microenvironments within the female genital tract, and
      that immune functions are affected by hormones as well as infections and
      inflammatory processes. To determine the distribution of mediators of CMI within
      the lower female genital tract, we have enumerated and characterized T-lymphocyte
      subsets and natural killer and antigen presenting cells (APCs; macrophages and
      dendritic cells) in the introitus, vagina, ectocervix, endocervix and cervical
      transformation zone (TZ) from healthy women, and have examined the effects of the
      menstrual cycle, menopause and inflammation on these parameters. In women without
      inflammation, T cells and APCs were most prevalent in the cervical TZ and
      surrounding tissue. Intraepithelial lymphocytes were predominantly CD8+ T cell+;
      most CD8+ cells in the TZ and endocervix, and a proportion of cells in the
      ectocervix, expressed T-cell internal antigen-1, a marker of cytotoxic potential.
      In contrast, the normal vaginal mucosa contained few T cells and APCs. Cervicitis
      and vaginitis cases had increased numbers of intraepithelial CD8+ and CD4+
      lymphocytes and APCs. The menstrual cycle and menopause had no apparent effect on
      cellular localization or abundance in any of the lower genital tract tissues.
      These data indicate that the cervix, especially the TZ, is the major inductive
      and effector site for CMI in the lower female genital tract. Because CD4+ T cells
      and APCs are primary host cells for human immunodeficiency virus type 1 (HIV-1),
      these data also provide further evidence that the cervix is a primary infection
      site of HIV-1, and that inflammation increases the risk of HIV transmission.

PMID- 16093360
TI  - Regulation of the Rhox5 homeobox gene in primary granulosa cells: preovulatory
      expression and dependence on SP1/SP3 and GABP.
AB  - Homeobox genes encode transcription factors that regulate embryonic development
      and postnatal events. Rhox5 (previously called Pem), the founding member of a
      homeobox gene cluster that we recently identified on the X chromosome, is
      selectively expressed in granulosa cells in the ovary and other somatic-cell
      types in other reproductive organs. In this report, we investigate its regulation
      in granulosa cells in the rat ovary. We found that Rhox5 expression in the ovary
      is governed by the Rhox5 distal promoter and is expressed at least as early as
      Day 5 postpartum. Rhox5 mRNA levels are regulated during the ovarian cycle,
      peaking before ovulation. Deletion analysis revealed a 25-nt element essential
      for distal promoter transcription in primary granulosa cells. This distal
      promoter element contains two ETS and one SP1 transcription-factor family binding
      sites that mutagenesis analysis indicated were essential for high-level
      transcription. This element was both necessary and sufficient for transcription,
      because it activated transcription when placed upstream of a heterologous minimal
      promoter. Cold competition and electrophoretic mobility shift assay studies
      demonstrated that SP1, SP3, and the ETS family transcription factor GABP bound
      this element. Dominant-negative forms of GABP and SP3 repressed distal promoter
      expression in primary rat granulosa, showing that these factors are crucial for
      Rhox5 expression. Cotransfection of dominant-negative mutants indicated that
      Rhox5 expression in granulosa cells is regulated by the c-Jun N-terminal protein
      kinase (JNK, MAPK8) and RAS pathways, which are known to be upstream of ETS
      family transcription factors. The discovery that Rhox5 expression in granulosa
      cells is regulated by MAPK pathways and ETS and SP1 family members provides an
      opportunity to understand how these regulatory pathways and factors collaborate
      to regulate gene expression during the ovarian cycle.

PMID- 16093361
TI  - Mice null for Frizzled4 (Fzd4-/-) are infertile and exhibit impaired corpora
      lutea formation and function.
AB  - Previous studies showed that transcripts encoding specific Wnt ligands and
      Frizzled receptors including Wnt4, Frizzled1 (Fzd1), and Frizzled4 (Fzd4) were
      expressed in a cell-specific manner in the adult mouse ovary. Overlapping
      expression of Wnt4 and Fzd4 mRNA in small follicles and corpora lutea led us to
      hypothesize that the infertility of mice null for Fzd4 (Fzd4-/-) might involve
      impaired follicular growth or corpus luteum formation. Analyses at defined stages
      of reproductive function indicate that immature Fzd4-/- mouse ovaries contain
      follicles at many stages of development and respond to exogenous hormone
      treatments in a manner similar to their wild-type littermates, indicating that
      the processes controlling follicular development and follicular cell responses to
      gonadotropins are intact. Adult Fzd4-/- mice also exhibit normal mating behavior
      and ovulate, indicating that endocrine events controlling these processes occur.
      However, Fzd4-/- mice fail to become pregnant and do not produce offspring.
      Histological and functional analyses of ovaries from timed mating pairs at Days
      1.5-7.5 postcoitus (p.c.) indicate that the corpora lutea of the Fzd4-/- mice do
      not develop normally. Expression of luteal cell-specific mRNAs (Lhcgr, Prlr,
      Cyp11a1 and Sfrp4) is reduced, luteal cell morphology is altered, and markers of
      angiogenesis and vascular formation (Efnb1, Efnb2, Ephb4, Vegfa, Vegfc) are low
      in the Fzd4-/- mice. Although a recently identified, high-affinity FZD4 ligand
      Norrin (Norrie disease pseudoglioma homolog) is expressed in the ovary, adult
      Ndph-/- mice contain functional corpora lutea and do not phenocopy Fzd4-/- mice.
      Thus, Fzd4 appears to impact the formation of the corpus luteum by mechanisms
      that more closely phenocopy Prlr null mice.

PMID- 16093362
TI  - Evidence that osteogenic progenitor cells in the human tunica albuginea may
      originate from stem cells: implications for peyronie disease.
AB  - Tissue ossification in Peyronie disease (commonly known as Peyronie's disease
      [PD]), a localized fibrotic lesion within the tunica albuginea (TA) of the penis,
      may result from osteogenic differentiation of fibroblasts, myofibroblasts, and/or
      adult stem cells in the TA, and may be triggered by chronic inflammation,
      oxidative stress, and profibrotic factors like transforming growth factor beta 1
      (TGFB1). In this study, we have investigated whether cultures of cells from
      normal TA and PD plaques undergo osteogenesis, express markers for stem cells,
      and originate other cell lineages via processes modulated by TGFB1. We found that
      TA and PD cells in osteogenic medium (OM) expressed osteogenic markers, alkaline
      phosphatase, and osteopontin and underwent calcification. PD cells, but not TA
      cells, formed foci in soft agar that were positive for alkaline phosphatase and
      calcification and expressed the mRNAs for osteoblast-specific factors
      pleiotrophin and periostin and bone morphogenic protein 2. Both cultures
      expressed stem cell marker CD34 antigen but not protein tyrosine phosphatase,
      receptor type c. TA and PD cells expressed smooth-muscle cell markers smoothelin
      and transgelin. None of the cultures underwent adipogenesis in adipogenic medium.
      Incubation with TGFB1 increased osteogenesis and myofibroblast differentiation
      and reduced CD34 antigen expression in both cultures. TA and PD cells modulated
      the differentiation of the multipotent C3H 10T(1/2) cells in dual cultures, into
      osteoblasts and myofibroblasts. In conclusion, both TA and PD cultures contain
      cells, presumably stem cells, that undergo osteogenic and myofibroblast
      differentiation, and may induce these processes by paracrine interactions. This
      may explain progression of fibrosis in the PD plaque and its eventual
      calcification.

PMID- 16093363
TI  - Constitutive eNOS-derived nitric oxide is a determinant of endothelial junctional
      integrity.
AB  - Basal vascular endothelial permeability is normally kept low in part by the
      restrictiveness of interendothelial junctions (IEJs). We investigated the
      possible role of nitric oxide (NO) in controlling IEJ integrity and thereby
      regulating basal vascular permeability. We determined the permeability of
      continuous endothelia in multiple murine vascular beds, including lung
      vasculature, of wild-type mice, endothelial nitric oxide synthase (eNOS) null
      mice, and mice treated with NOS inhibitor N-nitro-L-arginine methyl ester (L
      NAME). Light and electron microscopic studies revealed that L-NAME treatment
      resulted in IEJs opening within a few minutes with a widespread response within
      30 min. We observed a 35% increase in transendothelial transport of albumin,
      using as tracer dinitrophenylated albumin in mouse lungs and other organs
      studied. To rule out the involvement of blood cells in the mechanism of increased
      endothelial permeability, vascular beds were flushed free of blood, treated with
      L-NAME, and perfused with the tracer. The open IEJs observed in these studies
      indicated a direct role for NO in preserving the normal structure of endothelial
      junctions. We also used the electron-opaque tracer lanthanum chloride to assess
      vascular permeability. Lanthanum chloride was presented by perfusion to various
      vascular beds of mice lacking NO. Open IEJs were seen only in capillary and
      venular endothelial segments of mice lacking NO, and there was a concomitant
      increase in vascular permeability to the tracer. Together, these data demonstrate
      that constitutive eNOS-derived NO is a crucial determinant of IEJ integrity and
      thus serves to maintain the low basal permeability of continuous endothelia.

PMID- 16093364
TI  - Inducible binding of PU.1 and interacting proteins to the Toll-like receptor 4
      promoter during endotoxemia.
AB  - We hypothesized that PU.1 and PU.1 interacting proteins (PIP) binding to the Toll
      like receptor 4 (TLR4) promoter is involved in endotoxin-induced upregulation of
      TLR4 gene expression. Our results employing chromatin immunoprecipitation assays
      indicate that PU.1 binds to the murine TLR4 promoter both in macrophage cells
      and, most importantly, in whole lung tissue. Treatment of RAW 264.7 cells with
      endotoxin induced the association of PU.1 and the TLR4 promoter in a time
      dependent manner, and this was closely tied to interactions between the TLR4
      promoter and the PIP interferon regulatory factors (IRF)4 and IRF8. PU.1 binding
      was related to increases in steady-state TLR4 mRNA and total TLR4 protein in RAW
      cells. Endotoxemia in animals caused the similar inducible interaction between
      PU.1 and IRF4 and the TLR4 promoter in lung tissue of mice that was treated with
      a single intraperitoneal injection of endotoxin. PU.1 binding to the TLR4
      promoter was not enhanced in the lung tissue of endotoxin-resistant C3H/HeJ mice
      in response to endotoxemia. Transient transfection studies in RAW cells indicate
      that inducible binding of PU.1 to the TLR4 promoter is abrogated by a Ser148 to
      Ala mutation in PU.1. These data suggest that induction of PU.1/PIP binding to
      the TLR4 promoter is involved in endotoxin response in vivo and may mediate
      transcriptional changes in TLR4 gene expression.

PMID- 16093365
TI  - Functional assessment of multiple P-glycoprotein (P-gp) probe substrates:
      influence of cell line and modulator concentration on P-gp activity.
AB  - Compounds known to modulate P-glycoprotein (P-gp) activity were evaluated in cell
      monolayers expressing P-gp for their effects on the secretory transport of P-gp
      substrates paclitaxel, vinblastine, and digoxin. Paclitaxel has been proposed to
      selectively interact with a binding site on P-gp that is distinct from the
      vinblastine and digoxin-binding site. Using Madin-Darby canine kidney (MDCK)
      multidrug resistance-1 (MDR1), MDCK-wild-type (WT), and Caco-2 cell monolayers,
      the basal-to-apical (BL-AP) apparent permeability (Papp) of [3H]paclitaxel,
      [3H]vinblastine, and [3H]digoxin in the presence of various concentrations of a
      series of structurally diverse P-gp substrates and modulators of P-gp function
      were determined. MDCK-WT cell monolayers demonstrated active secretory transport
      of all P-gp substrate probes, although the sensitivity to inhibition by verapamil
      was lower than that demonstrated in MDCK-MDR1 cell monolayers. When evaluated as
      competitive inhibitors, several known P-gp substrates had no effect or only a
      slight modulatory effect on the BL-AP Papp of all probe substrates in MDCK-MDR1
      cells. The secretory transport of P-gp substrates in MDCK-WT cells was more
      sensitive to inhibition by known P-gp modulators compared with MDCK-MDR1 cells.
      Low concentrations of ketoconazole (1-3 microM) activated the BL-AP Papp of
      [3H]vinblastine and [3H]digoxin in MDCK-MDR1 cells but not in MDCK-WT or Caco-2
      cells. Determination of secretory transport in P-gp expressing cell monolayers,
      such as MDCK-MDR1 and Caco-2, may be complicated by substrate cooperativity and
      allosteric binding, which may result in the activation of P-gp. In addition,
      expression of other efflux transporters in these cell lines introduces additional
      complexity in distinguishing which transporter is responsible for substrate
      recognition and transport.

PMID- 16093366
TI  - What is qualitative research?

PMID- 16093367
TI  - Institutional narratives in the discourse between oncology social workers and
      cancer patients' self-help organization.
AB  - In this study, the authors examine a discourse between members of a cancer
      patients' self-help organization (CP-SHO) and oncological social workers (OSWs)
      on support groups for cancer patients. Eight OSWs and 8 CP-SHO volunteers served
      as the key research population. Using the interpretive-narrative approach to
      research, the authors apply a variety of data collection methods and a
      combination of data analysis methods: narrative analysis and discourse analysis.
      The findings point to the simultaneous existence of two institutional narratives
      for each organization, one internal and the other external. Discourse between the
      organizations takes place mainly at the external institutional narrative level,
      with each body maintaining the mistaken impression that the other's perception of
      reality is similar to its own (false consensus). In the meantime, the internal
      narratives that attest to the latent meaning of the discourse govern the
      interaction and prevent effective dialogue between the respective organizations.

PMID- 16093368
TI  - The craft of care: family care of relatives with advanced dementia.
AB  - Family caregiving is attracting more attention from policy makers and service
      providers, but managing a chronic condition in the home is a very complex
      activity that usually remains invisible to health care professionals. The study's
      purpose was to identify strategies family caregivers used in the home to care for
      their relatives who have dementia. The author collected data from interviews with
      18 caregivers and 2 health care professionals, and from participant observation
      in caregivers' support groups and homes. She used constant comparison analysis
      and describes the Craft of Care, a category that emerged during qualitative
      analysis. Caregivers craft care by creating ruses in care, a language to
      communicate, and spaces and devices for caregiving. They sustain the humanity of
      the patient in the midst of a condition that tends to destroy it.

PMID- 16093369
TI  - Speech impairment in the postoperative head and neck cancer patient: nurses' and
      patients' perceptions.
AB  - Communication between postoperative head and neck cancer patients with speech
      impairment and their health care providers is challenging. These challenges
      emerge during a period when the patient must communicate needs related to
      symptoms such as pain or concerns of significance in the absence of the
      traditional communication process. Content analysis methods facilitated
      understanding of the perspective of the postoperative head and neck cancer
      patient experiencing pain and a speech impairment, and the examination of the
      nurses' view in the assessment and management of this population. The authors
      identified self-report of pain as a critical component of pain assessment
      regardless of the presence of a speech impairment. Significant levels of
      frustration were associated with the nurses' goal of addressing the pain
      management needs of the speech impaired and the patients' pursuit of reporting
      the uniqueness of their pain experience.

PMID- 16093370
TI  - Manifestations of enduring during interviews with sexual assault victims.
AB  - The retelling of a sexual assault, whether during sexual assault care or law
      enforcement interviews, or in the process of seeking social support, is an
      emotionally stressful event, yet there is little research describing the
      psychological experiences of retelling. In a study of barriers to sexual assault
      care, 43 survivors recounted 76 assault events during individual interviews.
      Although assaults occurred from 1 to 15 years prior to the interview,
      participants demonstrated emotional upset. Using the praxis theory of suffering
      as a scaffold, the author describes manifestations of enduring and emotional
      suffering. The separation of enduring from emotional suffering indicates
      potential usefulness of the praxis theory of suffering in the provision of post
      sexual assault care.

PMID- 16093371
TI  - Constructing the stroke: sudden-onset narratives of stroke survivors.
AB  - In this article, the authors explore the narrative production of stroke from the
      perspectives of survivors, that is, the stroke itself, not its implications for
      the individual poststroke. In the vast amount of literature on both sudden onset
      and chronic illness, the narrative construction of the onset of the illness, for
      the most part, has been ignored by social scientists, most notably in qualitative
      research. This is certainly true of stroke. Drawing on existing literature in
      both chronic illness and the body, the authors extend this to explore the
      phenomenological construction of stroke onset. Using data gathered from in-depth
      interviews with 111 stroke survivors postdischarge, they suggest three narrative
      mechanisms are used in the construct of the sudden-onset event itself: the use of
      typifications to construct the body during stroke, stroke as an internal
      communicative act, and stroke as a physical sensation and the mechanisms used to
      minimize bodily concerns.

PMID- 16093372
TI  - Interaction patterns of adolescents with depression and the important adults in
      their lives.
AB  - The purpose of this study is to describe common interaction patterns between
      adolescents who are depressed and the important adults in their lives, with
      special attention given to interactions that influence the course of the teens'
      depression. Data are drawn from an ongoing grounded theory study of the
      management strategies and service usage patterns of adolescents who are
      depressed. The sample includes 52 young adults between the ages of 18 and 21 who
      experienced depressive symptoms as adolescents, 4 of their parents, and 8
      professionals who work with youths. All participants discussed how both
      adolescents and adults ignore, hide, or minimize the adolescents'distress by
      putting up a facade. The three common interaction patterns that were identified
      (maintaining the facade, poking holes in the facade, breaking down the facade)
      are responses to the facade. The author discusses interaction patterns and their
      influence on the course of the adolescents' depression.

PMID- 16093373
TI  - What is dialogical research, and why should we do it?
AB  - Social scientists have explored the writing of Russian literary philosopher
      Bakhtin from a variety of perspectives, but little attempt has been made to apply
      Bakhtin's conception of dialogue to the conduct of research and the production of
      research reports. The author's questions relate to what dialogical research would
      look like and the ethical imperative of dialogical research.

PMID- 16093374
TI  - Mood and narrative entwinement: some implications for educational practice.
AB  - Moods are one way of existentially reading the authenticity of people and are
      entwined within any narrative. Attunement between narrative and its mood is
      crucial for understanding the implicit message of the narrator. Sometimes, a
      master narrative is interrupted by counternarratives, so that narrative
      recognition becomes problematic. People can disguise their existential state when
      narrating, but the mood discloses it nonetheless. The authors explore the
      relationship between mood and narrative, and how the two are connected with how a
      person acts authentically or inauthentically. They provide selected empirical
      examples of narratives from medical students to support their argument. The
      educational relevance of their discussion comprises the final section. Educators
      in any educational program must first reflect on, then make explicit the manner
      in which narrative and mood are used to communicate knowledge.

PMID- 16093375
TI  - Participant diaries as a source of data in research with older adults.
AB  - Solicited participant diaries are an excellent source of data that has not been
      given sufficient attention as a data collection strategy for qualitative
      research. In a recent grounded theory study designed to explore strategies used
      by older adults to manage their chronic health problems, solicited diaries, when
      combined with an initial and follow-up interview, provided a rich source of data
      about day-to-day activities of participants. There were three options for
      maintaining the diary: written, audiotaped, or telephone conversation. The
      solicited diaries were guided by a set of open-ended questions designed to
      encourage participants to focus on daily activities and reflect on their values.
      The authors provide examples of data from participant diaries and suggestions for
      incorporating solicited participant diaries into data collection strategies for
      qualitative research.

PMID- 16093376
TI  - To the editor.

PMID- 16093378
TI  - Olig2 directs astrocyte and oligodendrocyte formation in postnatal subventricular
      zone cells.
AB  - The subventricular zone (SVZ) in the neonatal mammalian forebrain simultaneously
      generates olfactory interneurons, astrocytes, and oligodendrocytes. The molecular
      cues that enable SVZ progenitors to generate three distinct cell lineages without
      a temporal switching mechanism are not known. Here, we demonstrate that the basic
      helix-loop-helix transcription factor Olig2 plays a central role in this process.
      Olig2 is specifically expressed in gliogenic progenitors in the postnatal SVZ and
      by all glial lineages derived from this structure. By expressing normal and
      dominant-interfering forms of Olig2 in vivo, we show that Olig2 repressor
      function is both sufficient and necessary to prevent neuronal differentiation and
      to direct SVZ progenitors toward astrocytic and oligodendrocytic fates. Although
      Olig2 activity has been associated previously with motor neuron and
      oligodendrocyte development, our findings establish a previously unappreciated
      role for Olig2 in the development of astrocytes. Furthermore, these results
      indicate that Olig2 serves a critical role in pan-glial versus neuronal fate
      decisions in SVZ progenitors, making it the first intrinsic fate determinant
      shown to operate in the early postnatal SVZ.

PMID- 16093379
TI  - Phosphorylation of synapsin I by cAMP-dependent protein kinase controls synaptic
      vesicle dynamics in developing neurons.
AB  - In developing neurons, synaptic vesicles (SVs) undergo cycles of exo-endocytosis
      along isolated axons. However, it is currently unknown whether SV exocytosis is
      regulated before synaptogenesis. Here, we show that cAMP-dependent pathways
      affect SV distribution and recycling in the axonal growth cone and that these
      effects are mediated by the SV-associated phosphoprotein synapsin I. The presence
      of synapsin I on SVs is necessary for the correct localization of the vesicles in
      the central portion of the growth cone. Phosphorylation of synapsin I by cAMP
      dependent protein kinase (protein kinase A) causes the dissociation of the
      protein from the SV membrane, allowing diffusion of the vesicles to the periphery
      of the growth cone and enhancing their rate of recycling. These results provide
      new clues as to the bases of the well known activity of synapsin I in synapse
      maturation and indicate that molecular mechanisms similar to those operating at
      mature nerve terminals are active in developing neurons to regulate the SV life
      cycle before synaptogenesis.

PMID- 16093380
TI  - Abrupt maturation of a spike-synchronizing mechanism in neocortex.
AB  - Synchronous activity is common in the neocortex, although its significance,
      mechanisms, and development are poorly understood. Previous work showed that
      networks of electrically coupled inhibitory interneurons called low-threshold
      spiking (LTS) cells can fire synchronously when stimulated by metabotropic
      glutamate receptors. Here we found that the coordinated inhibition emerging from
      an activated LTS network could induce correlated spiking patterns among
      neighboring excitatory cells. Synchronous activity among LTS cells was absent at
      postnatal day 12 (P12) but appeared abruptly over the next few days. The rapid
      development of the LTS-synchronizing system coincided with the maturation of the
      inhibitory outputs and intrinsic membrane properties of the neurons. In contrast,
      the incidence and magnitude of electrical synapses remained constant between P8
      and P15. The developmental transformation of LTS interneurons into a synchronous,
      oscillatory network overlaps with the onset of active somatosensory exploration,
      suggesting a potential role for this synchronizing system in sensory processing.

PMID- 16093381
TI  - Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss
      of inhibition in lamina II of the dorsal horn after peripheral nerve injury.
AB  - We show that transsynaptic apoptosis is induced in the superficial dorsal horn
      (laminas I-III) of the spinal cord by three distinct partial peripheral nerve
      lesions: spared nerve injury, chronic constriction, and spinal nerve ligation.
      Ongoing activity in primary afferents of the injured nerve and glutamatergic
      transmission cause a caspase-dependent degeneration of dorsal horn neurons that
      is slow in onset and persists for several weeks. Four weeks after spared nerve
      injury, the cumulative loss of dorsal horn neurons, determined by stereological
      analysis, is >20%. GABAergic inhibitory interneurons are among the neurons lost,
      and a marked decrease in inhibitory postsynaptic currents of lamina II neurons
      coincides with the induction of apoptosis. Blocking apoptosis with the caspase
      inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) prevents
      the loss of GABAergic interneurons and the reduction of inhibitory currents.
      Partial peripheral nerve injury results in pain-like behavioral changes
      characterized by hypersensitivity to tactile or cold stimuli. Treatment with
      zVAD, which has no intrinsic analgesic properties, attenuates this neuropathic
      pain-like syndrome. Preventing nerve injury-induced apoptosis of dorsal horn
      neurons by blocking caspase activity maintains inhibitory transmission in lamina
      II and reduces pain hypersensitivity.

PMID- 16093382
TI  - Activity-dependent differential transmitter release in mouse adrenal chromaffin
      cells.
AB  - Chromaffin cells of the adrenal medulla are a primary neuroendocrine output of
      the sympathetic nervous system. When stimulated, they secrete a host of
      transmitter molecules, including catecholamines and neuropeptides, through the
      fusion of dense core secretory granules with the cell surface. At basal firing
      rates, set by the sympathetic tone, chromaffin cells selectively release
      catecholamines at a modest rate. Stress-mediated sympathetic activation leads to
      elevated catecholamine secretion and also evokes neuropeptide release.
      Catecholamines and neuropeptides are copackaged in the same granules; thus, it is
      unclear how this activity-dependent differential transmitter release is achieved.
      In this report, we use electrophysiological, electrochemical, fluorescence, and
      immunocytochemical approaches to quantify transmitter release under physiological
      electrical stimulation at the single cell level. We provide data to show that
      chromaffin cells selectively release catecholamine under basal firing conditions
      but release both neuropeptides and catecholamines under conditions that match
      acute stress. We further show that this differential transmitter release is
      achieved through a regulated activity-dependent dilation of the granule fusion
      pore. Thus, chromaffin cells may regulate release of different transmitters
      through a simple size-exclusion mechanism.

PMID- 16093383
TI  - A comparison of visceral and somatic pain processing in the human brainstem using
      functional magnetic resonance imaging.
AB  - Evidence from both human and animal studies has demonstrated a key role for
      brainstem centers in the control of ascending nociceptive input. Nuclei such as
      the rostral ventromedial medulla and periaqueductal gray (PAG) are able to both
      inhibit and facilitate the nociceptive response. It has been proposed that
      altered descending modulation may underlie many of the chronic pain syndromes
      (both somatic and visceral). We used functional magnetic resonance imaging to
      image the neural correlates of visceral and somatic pain within the brainstem.
      Ten healthy subjects were scanned twice at 3 tesla, during which they received
      matched, moderately painful, electrical stimuli to either the midline lower
      abdomen or rectum. Significant activation was observed in regions consistent with
      the PAG, nucleus cuneiformis (NCF), ventral tegmental area/substantia nigra,
      parabrachial nuclei/nucleus ceruleus, and red nucleus bilaterally to both
      stimuli. Marked spatial similarities in activation were observed for visceral and
      somatic pain, although significantly greater activation of the NCF (left NCF, p =
      0.02; right NCF, p = 0.01; Student's paired t test, two-tailed) was observed in
      the visceral pain group compared with the somatic group. Right PAG activity
      correlated with anxiety during visceral stimulation (r = 0.74; p < 0.05,
      Pearson's r, two-tailed) but not somatic stimulation. We propose that the
      differences in NCF and right PAG activation observed may represent a greater
      nocifensive response and greater emotive salience of visceral over somatic pain.

PMID- 16093384
TI  - Dopamine receptor stimulation modulates AMPA receptor synaptic insertion in
      prefrontal cortex neurons.
AB  - Addiction is believed to involve glutamate-dependent forms of synaptic plasticity
      that promote the formation of new habits focused on drug seeking. We used primary
      cultures of rat prefrontal cortex (PFC) neurons to explore mechanisms by which
      dopamine-releasing psychomotor stimulants such as cocaine and amphetamine
      influence synaptic plasticity, focusing on AMPA receptor trafficking because of
      its key role in long-term potentiation (LTP). Brief stimulation of D1 dopamine
      receptors increased surface expression of glutamate receptor 1 (GluR1)-containing
      AMPA receptors through a protein kinase A-dependent mechanism, by increasing
      their rate of externalization at extrasynaptic sites. Newly externalized GluR1
      remained extrasynaptic under basal conditions but could be translocated into
      synapses by subsequent NMDA receptor activation. These results suggest that D1
      receptors may facilitate LTP by increasing the AMPA receptor pool available for
      synaptic insertion. However, stimulation of D2 receptors decreased surface and
      synaptic GluR1 expression. These findings are discussed in the context of
      evidence that D1 and D2 receptors act independently rather than antagonistically
      in the intact PFC. D1 receptor facilitation of AMPA receptor synaptic insertion
      helps explain D1 receptor-dependent facilitation of LTP and learning in the
      normal brain. Abnormal engagement of this mechanism during unregulated dopamine
      release may account for maladaptive plasticity after repeated exposure to cocaine
      or amphetamine.

PMID- 16093385
TI  - Imaging experimental cerebral malaria in vivo: significant role of ischemic brain
      edema.
AB  - The first in vivo magnetic resonance study of experimental cerebral malaria is
      presented. Cerebral involvement is a lethal complication of malaria. To explore
      the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal
      magnetic resonance techniques were applied (imaging, diffusion, perfusion,
      angiography, spectroscopy). They reveal vascular damage including blood-brain
      barrier disruption and hemorrhages attributable to inflammatory processes. We
      provide the first in vivo demonstration for blood-brain barrier breakdown in
      cerebral malaria. Major edema formation as well as reduced brain perfusion was
      detected and is accompanied by an ischemic metabolic profile with reduction of
      high-energy phosphates and elevated brain lactate. In addition, angiography
      supplies compelling evidence for major hemodynamics dysfunction. Actually, edema
      further worsens ischemia by compressing cerebral arteries, which subsequently
      leads to a collapse of the blood flow that ultimately represents the cause of
      death. These findings demonstrate the coexistence of inflammatory and ischemic
      lesions and prove the preponderant role of edema in the fatal outcome of
      experimental cerebral malaria. They improve our understanding of the pathogenesis
      of cerebral malaria and may provide the necessary noninvasive surrogate markers
      for quantitative monitoring of treatment.

PMID- 16093386
TI  - Use-dependent inhibition of P2X3 receptors by nanomolar agonist.
AB  - P2X3 receptors desensitize within 100 ms of channel activation, yet recovery from
      desensitization requires several minutes. The molecular basis for this slow rate
      of recovery is unknown. We designed experiments to test the hypothesis that this
      slow recovery is attributable to the high affinity (< 1 nM) of desensitized P2X3
      receptors for agonist. We found that agonist binding to the desensitized state
      provided a mechanism for potent inhibition of P2X3 current. Sustained
      applications of 0.5 nM ATP inhibited > 50% of current to repetitive applications
      of P2X3 agonist. Inhibition occurred at 1000-fold lower agonist concentrations
      than required for channel activation and showed strong use dependence. No
      inhibition occurred without previous activation and desensitization. Our data are
      consistent with a model whereby inhibition of P2X3 by nanomolar [agonist] occurs
      by the rebinding of agonist to desensitized channels before recovery from
      desensitization. For several ATP analogs, the concentration required to inhibit
      P2X3 current inversely correlated with the rate of recovery from desensitization.
      This indicates that the affinity of the desensitized state and recovery rate
      primarily depend on the rate of agonist unbinding. Consistent with this
      hypothesis, unbinding of [32P]ATP from desensitized P2X3 receptors mirrored the
      rate of recovery from desensitization. As expected, disruption of agonist binding
      by site-directed mutagenesis increased the IC50 for inhibition and increased the
      rate of recovery.

PMID- 16093387
TI  - Coupled networks of parvalbumin-immunoreactive interneurons in the rat
      basolateral amygdala.
AB  - Recent studies indicate that the basolateral amygdala exhibits fast rhythmic
      oscillations during emotional arousal, but the neuronal mechanisms underlying
      this activity are not known. Similar oscillations in the cerebral cortex are
      generated by a network of parvalbumin (PV)-immunoreactive interneurons
      interconnected by chemical synapses and dendritic gap junctions. The present
      immunoelectron microscopic study revealed that the basolateral amygdalar nucleus
      (BLa) contains a network of parvalbumin-immunoreactive (PV+) interneurons
      interconnected by chemical synapses, dendritic gap junctions, and axonal gap
      junctions. Twenty percent of synapses onto PV+ neurons were formed by PV+ axon
      terminals. All of these PV+ synapses were symmetrical. PV+ perikarya exhibited
      the greatest incidence of PV+ synapses (30%), with lower percentages associated
      with PV+ dendrites (15%) and spines (25%). These synapses comprised half of all
      symmetrical synapses formed with PV+ cells. A total of 18 dendrodendritic gap
      junctions between PV+ neurons were observed, mostly involving secondary and more
      distal dendrites (0.5-1.0 microm thick). Dendritic gap junctions were often in
      close proximity to PV+ chemical synapses. Six gap junctions were observed between
      PV+ axon terminals. In most cases, one or both of these terminals formed synapses
      with the perikarya of principal neurons. This is the first study to describe
      dendritic gap junctions interconnecting PV+ interneurons in the basolateral
      amygdala. It also provides the first documentation of gap junctions between
      interneuronal axon terminals in the mammalian forebrain. These data provide the
      anatomical basis for a PV+ network that may play a role in the generation of
      rhythmic oscillations in the BLa during emotional arousal.

PMID- 16093388
TI  - Dopamine is a regulator of arousal in the fruit fly.
AB  - Sleep and arousal are known to be regulated by both homeostatic and circadian
      processes, but the underlying molecular mechanisms are not well understood. It
      has been reported that the Drosophila rest/activity cycle has features in common
      with the mammalian sleep/wake cycle, and it is expected that use of the fly
      genetic model will facilitate a molecular understanding of sleep and arousal.
      Here, we report the phenotypic characterization of a Drosophila rest/activity
      mutant known as fumin (fmn). We show that fmn mutants have abnormally high levels
      of activity and reduced rest (sleep); genetic mapping, molecular analyses, and
      phenotypic rescue experiments demonstrate that these phenotypes result from
      mutation of the Drosophila dopamine transporter gene. Consistent with the rest
      phenotype, fmn mutants show enhanced sensitivity to mechanical stimuli and a
      prolonged arousal once active, indicating a decreased arousal threshold.
      Strikingly,fmn mutants do not show significant rebound in response to rest
      deprivation as is typical for wild-type flies, nor do they show decreased life
      span. These results provide direct evidence that dopaminergic signaling has a
      critical function in the regulation of insect arousal.

PMID- 16093389
TI  - Deficits in trace fear memory and long-term potentiation in a mouse model for
      fragile X syndrome.
AB  - Trace fear memory requires the activity of the anterior cingulate cortex (ACC)
      and is sensitive to attention-distracting stimuli. Fragile X syndrome is the most
      common form of mental retardation with many patients exhibiting attention
      deficits. Previous studies in fragile X mental retardation 1 (FMR1) knock-out
      (KO) mice, a mouse model for fragile X, focused mainly on hippocampal-dependent
      plasticity and spatial memory. We demonstrate that FMR1 knock-out mice show a
      defect in trace fear memory without changes in locomotion, anxiety, and pain
      sensitivity. Whole-cell path-clamp recordings in the ACC show that long-term
      potentiation (LTP) was completely abolished. A similar decrease in LTP was found
      in the lateral amygdala, another structure implicated in fear memory. No
      significant changes were found in basal synaptic transmission. This suggests that
      synaptic plasticity in the ACC and amygdala of FMR1 KO mice plays an important
      role in the expression of behavioral phenotypes similar to the symptoms of
      fragile X syndrome.

PMID- 16093390
TI  - Bidirectional modulation of hippocampal long-term potentiation under stress and
      no-stress conditions in basolateral amygdala-lesioned and intact rats.
AB  - Hippocampal long-term potentiation (LTP) is widely considered as a cellular model
      for learning and memory formation. We have shown previously that protein
      synthesis-independent, early dentate gyrus (DG) LTP, lasting approximately 4-5 h,
      can be transformed into a late-LTP with a duration of > or = 24 h by a brief
      acute swim stress experience (high-stress condition). This reinforcement requires
      the activation of mineralocorticoid receptors and protein synthesis. The
      basolateral amygdala (BLA) is known to modulate glucocorticoid effects on the
      consolidation of spatial/contextual memory via a beta-adrenergic mechanism.
      Interestingly, hippocampal DG-LTP can also be indirectly modulated by beta
      adrenergic and cholinergic/muscarinergic processes. Here, we show that the
      reinforcement of early-DG-LTP under high-stress conditions depends on the
      processing of novel spatial/contextual information. Furthermore, this
      reinforcement was blocked in BLA-lesioned animals compared with sham-operated and
      intact controls; however, it was not dependent on beta-adrenergic or
      cholinergic/muscarinergic receptor activation. In contrast, under low-stress
      conditions, the induction of late-LTP in BLA-lesioned animals is facilitated, and
      this facilitation, again, was dependent on beta-adrenergic activation. The data
      suggest that DG-LTP maintenance can be influenced by the BLA through different
      mechanisms: a short-lasting corticosterone-dependent and beta-adrenergic
      independent mechanism and a long-lasting mechanism that facilitated hippocampal
      beta-adrenergic mechanisms.

PMID- 16093391
TI  - How to enhance ipsilateral actions of pyramidal tract neurons.
AB  - We have shown previously that ipsilateral pyramidal tract (PT) neurons facilitate
      the actions of reticulospinal neurons on feline motoneurons (Edgley et al.,
      2004), which indicates that they might assist the recovery of motor functions
      after injuries of contralateral corticospinal neurons. Nevertheless, stimulation
      of ipsilateral PT fibers alone only rarely evoked any synaptic actions in
      motoneurons. The aim of this study was to investigate possible ways of enhancing
      such actions and of inducing more effective excitation and inhibition of
      motoneurons. The effects of stimulation of the ipsilateral PT were investigated
      after eliminating the spinal actions of contralateral PT fibers by hemisecting
      the spinal cord at a low thoracic level and were estimated from intracellular
      records from hindlimb motoneurons. Two measures were used to enhance PT actions.
      The first was to increase the probability of activation of reticulospinal neurons
      by mutual facilitation of actions of ipsilateral and contralateral PT neurons.
      The second was to enhance synaptic transmission between PT neurons and
      reticulospinal neurons, and in pathways between the reticulospinal neurons and
      motoneurons via commissural interneurons, by systemic application of a K+ channel
      blocker, 4-aminopyridine (4-AP). The results show that under favorable
      conditions, ipsilateral PT neurons may induce EPSPs and IPSPs in hindlimb
      motoneurons, or even action potentials, via the reticulospinal pathway. This
      study strengthens previous conclusions that ipsilateral PT neurons can
      potentially replace, at least to some extent, the actions of injured
      contralateral PT neurons. It also suggests that 4-AP might improve the progress
      of the recovery.

PMID- 16093392
TI  - Mechanisms of neuropeptide Y, peptide YY, and pancreatic polypeptide inhibition
      of identified green fluorescent protein-expressing GABA neurons in the
      hypothalamic neuroendocrine arcuate nucleus.
AB  - The fast inhibitory transmitter GABA is robustly expressed in the arcuate nucleus
      (ARC) and appears to play a major role in hypothalamic regulation of endocrine
      function and energy homeostasis. Previously, it has not been possible to record
      selectively from GABA cells, because they have no defining morphological or
      physiological characteristics. Using transgenic mice that selectively express GFP
      (green fluorescent protein) in GAD67 (glutamic acid decarboxylase 67)
      synthesizing cells, we identified ARC GABA neurons (n > 300) and used whole-cell
      recording to study their physiological response to neuropeptide Y (NPY), the
      related peptide YY(3-36) (PYY(3-36)), and pancreatic polypeptide (PP), important
      modulators of ARC function. In contrast to other identified ARC cells in which
      NPY receptor agonists were reported to generate excitatory actions, we found that
      NPY consistently reduced the firing rate and hyperpolarized GABA neurons
      including neuroendocrine GABA neurons identified by antidromic median eminence
      stimulation. The inhibitory NPY actions were mediated by postsynaptic activation
      of G-protein-linked inwardly rectifying potassium (GIRK) and depression of
      voltage-gated calcium currents via Y1 and Y2 receptor subtypes. Additionally, NPY
      reduced spontaneous and evoked synaptic glutamate release onto GABA neurons by
      activation of Y1 and Y5 receptors. The peptide PYY(3-36), a peripheral endocrine
      signal that can act in the brain, also inhibited GABA neurons, including
      identified neuroendocrine cells, by activating GIRK conductances and depressing
      calcium currents. The endogenous Y4 agonist PP depressed the activity of GABA
      expressing neurons mainly by presynaptic attenuation of glutamate release.
      Together, these results show that the family of neuropeptide Y modulators reduces
      the activity of inhibitory GABA neurons in the ARC by multiple presynaptic and
      postsynaptic mechanisms.

PMID- 16093393
TI  - PolyADP-ribosylation is involved in neurotrophic activity.
AB  - PolyADP-ribosylation is a transient posttranslational modification of proteins,
      mainly catalyzed by poly(ADP-ribose)polymerase-1 (PARP-1). This highly conserved
      nuclear protein is activated rapidly in response to DNA nick formation and
      promotes a fast DNA repair. Here, we examine a possible association between
      polyADP-ribosylation and the activity of neurotrophins and neuroprotective
      peptides taking part in life-or-death decisions in mammalian neurons. The
      presented results indicate an alternative mode of PARP-1 activation in the
      absence of DNA damage by neurotrophin-induced signaling mechanisms. PARP-1 was
      activated in rat cerebral cortical neurons briefly exposed to NGF-related nerve
      growth factors and to the neuroprotective peptides NAP (the peptide NAPVSIPQ,
      derived from the activity-dependent neuroprotective protein ADNP) and ADNF-9 (the
      peptide SALLRSIPA, derived from the activity-dependent neurotrophic factor ADNF)
      In addition, polyADP-ribosylation was involved in the neurotrophic activity of
      NGF-induced and NAP-induced neurite outgrowth in differentiating pheochromocytoma
      12 cells as well as in the neuroprotective activity of NAP in neurons treated
      with the Alzheimer's disease neurotoxin beta-amyloid. A fast loosening of the
      highly condensed chromatin structure by polyADP-ribosylation of histone H1, which
      renders DNA accessible to transcription and repair, may underlie the role of
      polyADP-ribosylation in neurotrophic activity.

PMID- 16093395
TI  - Stargazin modulates native AMPA receptor functional properties by two distinct
      mechanisms.
AB  - AMPA receptors play a central role in basal excitatory synaptic transmission as
      well as synaptic maturation and plasticity. The transmembrane AMPA receptor
      regulatory protein (TARP) stargazin (gamma2) serves multiple roles in trafficking
      and stabilizing synaptic AMPA receptors and may be incorporated as an auxiliary
      subunit. We wanted to determine whether stargazin altered channel function of
      neuronal AMPA receptors. Transfection of cultured hippocampal neurons with
      stargazin produced two distinct effects on AMPA receptor functional properties: a
      sixfold reduction in glutamate-evoked desensitization and a twofold increase in
      the relative size of responses to the partial agonist kainate. Kinetic and dose
      response analyses suggest that the effect of stargazin on glutamate
      desensitization results from an allosteric interaction that destabilizes the
      desensitized state of the receptor and that potentiation of kainate responses
      reflects increased efficacy rather than a change in affinity. These functional
      effects were also observed in human embryonic kidney 293 cells transfected with
      various heteromeric and homomeric AMPA receptors, with distinct subunit-dependent
      effects on glutamate desensitization, kainate efficacy, and trafficking. Two
      regions of stargazin mediate its functional effects: the C-terminal intracellular
      domain seems to be more important for effects on glutamate-evoked desensitization
      and receptor trafficking, whereas the first extracellular domain makes a larger
      contribution to effects on kainate efficacy. These data indicate that TARPs are
      involved both in trafficking and direct modulation of channel function and, as
      auxiliary subunits of neuronal AMPA receptors, must be considered in the
      functional heterogeneity of neuronal AMPA receptors.

PMID- 16093394
TI  - Prefrontal control of the amygdala.
AB  - Accumulating evidence indicates that phobic and posttraumatic anxiety disorders
      likely result from a failure to extinguish fear memories. Extinction normally
      depends on a new learning that competes with the original fear memory and is
      driven by medial prefrontal cortex (mPFC) projections to the amygdala. Although
      mPFC stimulation was reported to inhibit the central medial (CEm) amygdala
      neurons that mediate fear responses via their brainstem and hypothalamic
      projections, it is unclear how this inhibition is generated. Because the mPFC has
      very sparse projections to CEm output neurons, the mPFC-evoked inhibition of the
      CEm is likely indirect. Thus, this study tested whether it resulted from a
      feedforward inhibition of basolateral amygdala (BLA) neurons that normally relay
      sensory inputs to the CEm. However, our results indicate that mPFC inputs excite
      rather than inhibit BLA neurons, implying that the inhibition of CEm cells is
      mediated by an active gating mechanism downstream of the BLA.

PMID- 16093396
TI  - Cholinergic suppression of KCNQ channel currents enhances excitability of
      striatal medium spiny neurons.
AB  - In response to glutamatergic synaptic drive, striatal medium spiny neurons in
      vivo transition to a depolarized "up state" near spike threshold. In the up
      state, medium spiny neurons either depolarize enough to spike or remain below
      spike threshold and are silent before returning to the hyperpolarized "down
      state." Previous work has suggested that subthreshold K+ channel currents were
      responsible for this dichotomous behavior, but the channels giving rise to the
      current and the factors determining its engagement have been a mystery. To move
      toward resolution of these questions, perforated-patch recordings from medium
      spiny neurons in tissue slices were performed. K+ channels with pharmacological
      and kinetic features of KCNQ channels potently regulated spiking at up-state
      potentials. Single-cell reverse transcriptase-PCR confirmed the expression of
      KCNQ2, KCNQ3, and KCNQ5 mRNAs in medium spiny neurons. KCNQ channel currents in
      these cells were potently reduced by M1 muscarinic receptors, because the effects
      of carbachol were blocked by M1 receptor antagonists and lost in neurons lacking
      M1 receptors. Reversal of the modulation was blocked by a phosphoinositol 4
      kinase inhibitor, indicating a requirement for phosphotidylinositol 4,5
      bisphosphate resynthesis for recovery. Inhibition of protein kinase C reduced the
      efficacy of the muscarinic modulation. Finally, acceleration of cholinergic
      interneuron spiking with 4-aminopyridine mimicked the effects of exogenous
      agonist application. Together, these results show that KCNQ channels are potent
      regulators of the excitability of medium spiny neurons at up-state potentials,
      and they are modulated by intrastriatal cholinergic interneurons, providing a
      mechanistic explanation for variability in spiking during up states seen in vivo.

PMID- 16093397
TI  - Cholecystokinin activates orexin/hypocretin neurons through the cholecystokinin A
      receptor.
AB  - Orexin A and B are neuropeptides implicated in the regulation of
      sleep/wakefulness and energy homeostasis. The regulatory mechanism of the
      activity of orexin neurons is not precisely understood. Using transgenic mice in
      which orexin neurons specifically express yellow cameleon 2.1, we screened for
      factors that affect the activity of orexin neurons (a total of 21 peptides and
      six other factors were examined) and found that a sulfated octapeptide form of
      cholecystokinin (CCK-8S), neurotensin, oxytocin, and vasopressin activate orexin
      neurons. The mechanisms that underlie CCK-8S-induced activation of orexin neurons
      were studied by both calcium imaging and slice patch-clamp recording. CCK-8S
      induced inward current in the orexin neurons. The CCKA receptor antagonist
      lorglumide inhibited CCK-8S-induced activation of orexin neurons, whereas the
      CCKB receptor agonists CCK-4 (a tetrapeptide form of cholecystokinin) and
      nonsulfated CCK-8 had little effect. The CCK-8S-induced increase in intracellular
      calcium concentration was eliminated by removing extracellular calcium but not by
      an addition of thapsigargin. Nifedipine, omega-conotoxin, omega-agatoxin, 4
      ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride, and SNX-482 had
      little effect, but La3+, Gd3+, and 2-aminoethoxydiphenylborate inhibited CCK-8S
      induced calcium influx. Additionally, the CCK-8S-induced inward current was
      dramatically enhanced in the calcium-free solution and was inhibited by the
      cation channel blocker SKF96365, suggesting an involvement of extracellular
      calcium-sensitive cation channels. CCK-8S did not induce an increase in
      intracellular calcium concentration when membrane potential was clamped at -60
      mV, suggesting that the calcium increase is induced by depolarization. The
      evidence presented here expands our understanding of the regulation of orexin
      neurons and the physiological role of CCK in the CNS.

PMID- 16093398
TI  - Distinct fibroblast growth factor (FGF)/FGF receptor signaling pairs initiate
      diverse cellular responses in the oligodendrocyte lineage.
AB  - Fibroblast growth factors (FGFs) have been implicated in numerous cellular
      processes, including proliferation, migration, differentiation, and survival.
      Whereas FGF-2, the prototypic ligand in a family of 22 members, activates all
      four tyrosine kinase FGF receptors (FGFR1-FGFR4), other members demonstrate a
      higher degree of selectivity. Oligodendrocytes (OLs), the myelin-producing cells
      of the CNS, are highly influenced by FGF-2 at all stages of their development.
      However, how other FGFs and their cognate receptors orchestrate the development
      of OLs is essentially undefined. Using a combination of specific FGF ligands and
      receptor blocking antibodies, we now show that FGF-8 and FGF-17 target OL
      progenitors, inhibiting their terminal differentiation via the activation of
      FGFR3, whereas FGF-9 specifically targets differentiated OLs, triggering
      increases in process growth via FGFR2 signaling; FGF-18 targets both OL
      progenitors and OLs via activation of both FGFR2 and FGFR3. These events are
      highly correlated with changes in FGF receptor expression from FGFR3 to FGFR2 as
      OL progenitors differentiate into mature OLs. In addition, we demonstrate that,
      although activation of FGFR1 by FGF-2 leads to proliferation of OL progenitors,
      it produces deleterious effects on differentiated OLs (i.e., aberrant reentry
      into cell cycle and down-regulation of myelin proteins with a loss of myelin
      membrane). These data suggest that ligand availability, coupled with changes in
      FGF receptor expression, yield a changing repertoire of ligand-receptor signaling
      complexes that contribute critically to the regulation of both normal OL
      development and potential OL/myelin pathogenesis.

PMID- 16093399
TI  - Anthropometric characteristics, dietary patterns and risk of type 2 diabetes
      mellitus in Vietnam.
AB  - OBJECTIVE: To determine the impact of anthropometric characteristics and dietary
      patterns on Type 2 diabetes mellitus in Vietnam. METHODS: Data from 144 subjects
      (9m/39f newly diagnosed diabetics; 18m/78f control subjects) were analyzed in
      this case-control study. Height, weight, waist and hip circumferences and percent
      body fat were measured. Dietary intakes were assessed by 24-hour recall on three
      non-consecutive weekdays. Fasting blood samples were collected for the analysis
      of plasma glucose, fructosamine, protein and lipid concentrations. RESULTS:
      Although the body mass index (BMI, kg/m(2)) was similar between diabetic and
      control subjects, diabetic subjects had significantly greater percent body fat
      (31.1 +/- 5.8% vs. 27.7 +/- 6.2%) and waist-hip ratios (WHR, 0.91 +/- 0.07 vs.
      0.86 +/- 0.08). Diabetic subjects had higher intakes of protein (p < 0.01),
      especially animal protein (p < 0.001), and consumed more meat (p < 0.01) than
      control subjects. Percent body fat and WHR were positively associated with
      diabetes (odds ratios [OR] 1.53 [95%CI 1.29-1.79] and 1.09 [95% CI 0.89-1.58],
      respectively) as were protein intake (OR 1.21 [95% CI 1.12-1.31]) and animal
      protein intake (OR 1.18 [95% CI 1.10-1.26]). CONCLUSIONS: This study indicates
      that percent body fat and WHR are risk factors associated with diabetes even when
      the BMI is normal. Evolving dietary patterns with increasingly more protein and
      meat consumption may also contribute to the deterioration of glucose metabolism
      among Vietnamese people.

PMID- 16093400
TI  - Estrogenic effect of yam ingestion in healthy postmenopausal women.
AB  - OBJECTIVE: Yam (Dioscorea) has been used to treat menopausal symptom
      folklorically. This study was to investigate the effects of yam ingestion on
      lipids, antioxidant status, and sex hormones in postmenopausal women. METHODS:
      Twenty-four apparently healthy postmenopausal women were recruited to replace
      their staple food (rice for the most part) with 390 g of yam (Dioscorea alata) in
      2 of 3 meals per day for 30 days and 22 completed the study. Fasting blood and
      first morning urine samples were collected before and after yam intervention for
      the analyses of blood lipids, sex hormones, urinary estrogen metabolites and
      oxidant stress biomarker. The design was a one arm, pre-post study. A similar
      study of postmenopausal women (n = 19) fed 240 g of sweet potato for 41 days was
      included as a control study. Serum levels of estrone, estradiol and SHBG were
      analyzed for this control group. RESULTS: After yam ingestion, there were
      significant increases in serum concentrations of estrone (26%), sex hormone
      binding globulin (SHBG) (9.5%), and near significant increase in estradiol (27%).
      No significant changes were observed in serum concentrations of
      dehydroepiandrosterone sulfate, androstenedione, testosterone, follicular
      stimulating hormone, and luteinizing hormone. Free androgen index estimated from
      the ratio of serum concentrations of total testosterone to SHBG decreased.
      Urinary concentrations of the genotoxic metabolite of estrogen, 16alpha
      hydroxyestrone decreased significantly by 37%. Plasma cholesterol concentration
      decreased significantly by 5.9%. Lag time of low-density lipoprotein oxidation
      prolonged significantly by 5.8% and urinary isoprostane levels decreased
      significantly by 42%. For the control subjects fed with sweet potato, all three
      hormone parameters measured were not changed after intervention. CONCLUSION:
      Although the exact mechanism is not clear, replacing two thirds of staple food
      with yam for 30 days improves the status of sex hormones, lipids, and
      antioxidants. These effects might reduce the risk of breast cancer and
      cardiovascular diseases in postmenopausal women.

PMID- 16093401
TI  - Effects of binge eating behavior on fuel oxidation and body composition.
AB  - OBJECTIVE: To investigate energy expenditure and glucose metabolism after a
      standard oral glucose load (75 g) in 8 normal weight bulimic women and 8 normal
      weight control women and to evaluate the relative endocrine implication. DESIGN:
      Serum glucose and insulin were measured both in basal conditions and after the
      glucose load; a basal endocrine assessment and body composition was evaluated and
      glucose induced thermogenesis (GIT) was calculated during 300 min following the
      glucose load. RESULTS: Serum glucose levels were significantly lower in bulimics
      both in fasting and in post-prandial state. Insulin levels were similar in
      bulimic and control women before and after the glucose load. FSH, leptin and free
      urinary cortisol (FUC) were all within the normal ranges, but significantly lower
      in bulimic patients compared with controls (p < 0.001). Fat mass (FM) and Fat
      free mass (FFM) were reduced in bulimic patients, even if they normalized after
      correction per body weight. Resting energy expenditure (REE) was similar in the
      two groups even after FFM normalization, while GIT was lower in bulimic patients
      and it was strongly related to free urinary chortisol. Glucose oxidation was
      higher in fasting state and post glucose load, while lipid oxidation was strongly
      reduced. CONCLUSION: An energy preservation mechanism seems to be the key element
      for normal-weight bulimic patients' metabolism, consisting in leptin levels and
      GIT reduction, and lipid oxidation inhibition.

PMID- 16093402
TI  - Toenail selenium and cardiovascular disease in men with diabetes.
AB  - OBJECTIVE: Selenium as a component of glutathione peroxidase may be beneficial in
      insulin resistance, hence potentially may modify the risk of diabetes and
      cardiovascular disease (CVD). The aim of this study is to evaluate the
      association between toenail selenium and CVD among men with diabetes. METHODS: We
      performed cross-sectional and nested case-control analyses within the Health
      Professionals Follow-up Study, a cohort of men aged 40 to 75 years in 1986. The
      cross-sectional analysis compared healthy controls (n = 361) to men with diabetes
      only (n = 688), and men with prevalent diabetes and CVD (n = 198). The nested
      case-control study included 202 diabetic men who developed incident CVD during
      follow-up and 361 matched controls. RESULTS: After controlling for potential
      confounders, the odds ratio (OR) for prevalent diabetes was 0.43 (95% CI: 0.28,
      0.64; p-trend <0.001) for the highest compared to the lowest quartile of
      selenium. Comparison between diabetic men with CVD and healthy controls yielded
      an OR of 0.86 (95% CI: 0.47, 1.56, p-trend = 0.37) between extreme quartiles. In
      the nested case-control analysis, the OR between extreme quartiles was 0.57 (95%
      CI: 0.29, 1.03; p-trend = 0.07), comparing diabetic men with incident CVD to
      healthy controls. CONCLUSIONS: Our results suggest that levels of toenail
      selenium are lower among diabetic men with or without CVD than among healthy
      controls. However, this study could not distinguish between the effects of
      selenium on diabetes and those on CVD. Randomized clinical trials are needed to
      study potential benefits of selenium supplementation in the prevention and
      treatment of diabetes and CVD.

PMID- 16093403
TI  - Effect of powdered fermented milk with Lactobacillus helveticus on subjects with
      high-normal blood pressure or mild hypertension.
AB  - OBJECTIVE: Two tripeptides (Val-Pro-Pro and Ile-Pro-Pro) that have inhibitory
      activities for angiotensin I-converting enzyme are produced in milk fermented
      with Lactobacillus helveticus. In this study we evaluated the effect and safety
      of powdered fermented milk with L. helveticus CM4 on subjects with high-normal
      blood pressure or mild hypertension. METHODS: A randomized, placebo-controlled,
      double-blind study was conducted using 40 subjects with high-normal blood
      pressure (HN group) and 40 subjects with mild hypertension (MH group). Each
      subject ingested 6 test tablets (12 g) containing powdered fermented milk with L.
      helveticus CM4 daily for 4 weeks (test group) or the same amount of placebo
      tablets for 4 weeks (placebo group). RESULTS: During treatment, the decrease in
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the test
      group tended to be greater than in the placebo group for both blood pressure
      groups. At the end of treatment (week 4), a significant decrease in DBP in the HN
      group was observed (i.e. 5.0 mm Hg (0.1, 9.9; p = 0.04) compared with the placebo
      group). There was no significant change in SBP (3.2 mm Hg (95% CI -2.6, 8.9; p =
      0.27). In the MH group, SBP decreased by 11.2 mm Hg (4.0, 18.4; p = 0.003) and
      there was a statistically non-significant decrease in DBP of 6.5 mm Hg (-0.1,
      13.0; p = 0.055) compared with the placebo group. No marked changes were observed
      in other indexes, including pulse rate, body weight and blood serum variables,
      and no adverse effects attributed to the treatment was found in each group.
      CONCLUSIONS: Daily ingestion of the tablets containing powdered fermented milk
      with L. helveticus CM4 in subjects with high-normal blood pressure or mild
      hypertension reduces elevated blood pressure without any adverse effects.

PMID- 16093404
TI  - The effect of folate fortification of cereal-grain products on blood folate
      status, dietary folate intake, and dietary folate sources among adult non
      supplement users in the United States.
AB  - OBJECTIVE: Since January 1998, the Federal Drug Administration has required folic
      acid fortification of all enriched cereal-grain products in the U.S. This program
      intended to increase folic acid intake among women of childbearing age in order
      to decrease their risk of pregnancies affected by neural tube defects. The aim of
      this study was to explore the changes in serum and erythrocyte folate status of
      the adult U.S. population following folic acid fortification of enriched cereal
      grain products and to explore accompanying changes in food sources and dietary
      total folate intake. METHODS: We compared data from two National Health and
      Nutrition Examination Surveys (NHANES): NHANES III, conducted during 1988 to
      1994, reflecting the time prior to folate fortification, and NHANES 1999-2000,
      reflecting the time period after fortification. RESULTS: Mandatory folic acid
      fortification led to significant increases in both serum and erythrocyte folate
      concentrations in all sex and age groups. In the overall study population the
      mean serum folate concentration increased more than two-fold (136%), from 11.4
      nmol/L to 26.9 nmol/L, and the mean erythrocyte folate concentration increased by
      57 percent, from 375 nmol/L to 590 nmol/L. Less than 10% of women of childbearing
      age reached the recommended erythrocyte folate concentration of greater than 906
      nmol/L that has been shown to be associated with a significant reduction in
      neural tube defect (NTD) risk. After fortification, the category "bread, rolls,
      and crackers" became the single largest contributor of total folate to the
      American diet, contributing 15.6% of total intake, surpassing vegetables, which
      were the number one folate food source prior to fortification. Dietary intake of
      total folate increased significantly in almost all sex and age groups, except in
      females over 60 years of age. The mean dietary total folate intake of the study
      population increased by 76 microg/d (28%), from 275 microg/d to 351 microg/d.
      CONCLUSIONS: The fortification of enriched cereal-grain products with folic acid
      led to a significant improvement of blood folate status of the overall adult, non
      supplement using, US population. However, women of childbearing age may take
      folic acid supplements to reach erythrocyte folate levels that have been
      associated with decreased risk of NTDs.

PMID- 16093405
TI  - Effect of soy protein containing isoflavones on blood lipids in moderately
      hypercholesterolemic adults: a randomized controlled trial.
AB  - BACKGROUND: Dietary intake of soy protein with isoflavones may be associated with
      reductions in serum cholesterol. OBJECTIVES: To compare the effects of a water
      washed soy protein concentrate with a milk-protein based control on blood lipid
      levels in hyperlipidemic men and women. METHODS: A randomized, double-blind,
      controlled clinical trial including 159 subjects. After a 3-week run-in period
      during which all subjects consumed a milk protein-based supplement, participants
      were randomized into one of two groups: a control group (continued milk protein)
      and an intervention group (soy protein) for a five-week period. Fasting venous
      blood draws for lipid measurement were obtained at baseline, towards the end of
      the run-in period and at the end of the intervention. Blood isoflavone
      concentrations were measured at the end of the study. RESULTS: Blood lipid levels
      were not significantly different between groups at any point in time; and there
      were no significant associations between blood isoflavones and lipid levels.
      Significant decreases in total cholesterol (19 mg/dL), and LDL-cholesterol (11
      mg/dL), were observed during the run-in period, with no further decreases in
      lipids during the intervention period in either group. CONCLUSIONS: These results
      do not support the hypothesis that water-washed soy protein has an effect on
      blood lipids. Several hypotheses are discussed, highlighting the selective nature
      of the effect of soy consumption in the population. The cholesterol-lowering
      effect during the run-in period may be explained by the "regression to the mean
      effect" and by other factors related to study participation, mainly nutrient
      displacement induced by the protein supplement.

PMID- 16093406
TI  - Saturated and cis- and trans-unsaturated fatty acids intake in rural and urban
      Costa Rican adolescents.
AB  - OBJECTIVE: The purpose of this study is to determine whether intake of saturated
      fatty acids and cis- and trans-unsaturated fatty acids is associated with an
      urban compared to a rural lifestyle, and whether these associations are
      responsible for differences in plasma lipid concentrations. METHODS: Two hundred
      seventy-five adolescents, aged 12 to 19 years, living in rural and urban areas of
      San Jose, Costa Rica, were included in the study. All participants completed
      three-day food records, provided a fasting blood sample, and carried out a
      modified Harvard Step Test. RESULTS: Compared to rural, urban adolescents
      reported higher intakes of energy-adjusted individual and total saturated fatty
      acids, total n-3, total n-6 (p < 0.05). Compared to rural, urban adolescents had
      higher intake of 18:1 (3.65 vs. 3.25, p = 0.0001) and 18:2 (0.62 vs. 0.80, p =
      0.001) trans fatty acids, as well as lower intake of carbohydrate (p < 0.05).
      Palm shortening was the main source of saturated fat (32%), and partially
      hydrogenated soybean oil used for cooking was the main source of n-3 fatty acids
      (33%), n-6 fatty acids (33%) and trans fatty acids (34%). Compared to rural,
      urban adolescents had lower systolic and diastolic blood pressure and higher
      plasma HDL cholesterol concentration (44 vs. 40 mg/dL, p < 0.0001), but were more
      likely to be sedentary (68% vs. 57%, p < 0.0001). Among environmental factors,
      higher carbohydrate intake was a significant determinant of a lower HDL
      cholesterol (beta coeff = -1.45, p = 0.04), while lauric and myristic fatty acids
      correlated with increased LDL cholesterol (beta coeff = 3.6, 1.7, p < 0.05).
      CONCLUSIONS: A diet containing less carbohydrate and less saturated fatty acids
      contributes to a more beneficial lipid profile in Costa Rican adolescents, but a
      trend towards high trans fatty acids intake, particularly in the urban area, is
      worrisome given the well-known adverse effects of trans fatty acids.

PMID- 16093407
TI  - A comparison of three dietary pattern indexes for predicting biomarkers of diet
      and disease.
AB  - OBJECTIVE: Examination of dietary indexes in association with objective
      biomarkers of dietary intake and chronic disease risk is an important step in
      their validation. We compared three dietary pattern indexes-Healthy Eating Index
      (HEI), Recommended Foods Score (RFS-24 hour recall), and Dietary Diversity Score
      for recommended foods (DDS-R)-for their ability to predict biomarkers of dietary
      intake, obesity, cardiovascular disease, and diabetes. METHODS: We used dietary
      and laboratory data from the third National Health and Nutrition Examination
      Survey to study these associations in 8719 disease-free adults aged > or =20 y.
      The HEI, developed by the USDA, was a sum of scores on consideration of ten
      individual components; the RFS was a sum of all recommended foods (lean meat,
      poultry and fish, whole grains, fruits and juices, low-fat dairy, and vegetables)
      mentioned in the recall; the DDS-R examined whether or not a recommended food was
      mentioned from each of the five major food groups. The independent association of
      the dietary pattern indexes with body mass index (BMI), blood pressure, and serum
      concentrations of several biomarkers were examined using regression methods to
      adjust for multiple covariates. RESULTS: All indexes were strong independent
      positive predictors of serum concentrations of vitamin C, E, folate, and all
      carotenoids (p < or = 0.00001), except lycopene, and were negative predictors of
      BMI, serum homocysteine, C-reactive protein, plasma glucose, and hemoglobin A1C
      (p < 0.05). The RFS and DDS-R were inversely associated with blood pressure and
      serum cholesterol (p < or = 0.03). CONCLUSIONS: The RFS and DDS-R performed as
      well or better than the HEI for predicting serum concentration of nutrients and
      biomarkers of disease risk.

PMID- 16093408
TI  - New therapeutic approaches to Parkinson's disease including neural transplants.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder of the brain and
      typically presents with a disorder of movement. The core pathological event
      underlying the condition is the loss of the dopaminergic nigrostriatal pathway
      with the formation of alpha-synuclein positive Lewy bodies. As a result, drugs
      that target the degenerating dopaminergic network within the brain work well at
      least in the early stages of the disease. Unfortunately, with time these
      therapies fail and produce their own unique side-effect profile, and this,
      coupled with the more diffuse pathological and clinical findings in advancing
      disease, has led to a search for more effective therapies. In this review, the
      authors will briefly discuss the emerging new drug therapies in PD before
      concentrating on a more detailed discussion on the state of cell therapies to
      cure PD.

PMID- 16093409
TI  - Severity of depressive symptoms and quality of life in patients with amyotrophic
      lateral sclerosis.
AB  - OBJECTIVES: The authors aimed at investigating the occurrence of depression and
      the level of quality of life in patients with amyotrophic lateral sclerosis
      (ALS), an incurable neurodegenerative disease leading to progressive motor
      paralysis. They further wished to elucidate correlates of depression and quality
      of life, such as physical impairment, time since diagnosis, age, sex, and
      education. Additionally, the authors attempted to confirm previous studies that
      had shown quality of life to be underestimated by partners or caregivers.
      METHODS: To assess severity of depressive symptoms, the authors used Beck's
      Depression Inventory (BDI) and the ALS-Depression Inventory. To assess the
      patients' quality of life, they used the Scales to Assess Quality of Life. The
      same questionnaire was presented to partners or caregivers to estimate the
      patients' quality of life. RESULTS: Severity of depressive symptoms was
      everything from not depressed to clinically relevant depressed. On average,
      quality of life was rated as satisfactory. Severity of depressive symptoms and
      quality of life showed a moderate positive relation to physical impairment and a
      weak negative relation to time since diagnosis. Partners or caregivers rated
      patients' quality of life significantly lower than did the patients. CONCLUSIONS:
      Although depression occurs among ALS patients, it is not inevitable. Patients can
      remain free of depression and maintain a good quality of life. Depression should
      be treated, and patients have to be provided with unbiased information, including
      their medical and palliative care options.

PMID- 16093410
TI  - The EXCITE trial: attributes of the Wolf Motor Function Test in patients with
      subacute stroke.
AB  - The Wolf Motor Function Test (WMFT) has been used in rehabilitation studies of
      chronic stroke patients, but until now its psychometric properties have not been
      evaluated in patients with subacute stroke. Two hundred twenty-nine participants
      with subacute stroke (3-9 months postinjury) at 7 research sites met inclusion
      criteria for the EXCITE Trial and were randomized into immediate or delayed (by 1
      year) constraint-induced movement therapy treatment. All evaluations were
      undertaken by assessors standardized in the administration of the WMFT and masked
      to treatment designation. Participants were also assessed using the Fugl Meyer
      Motor Assessment (FMA). Delayed group members had measurements repeated 2 weeks
      following baseline assessment to determine learning or exposure effects. The
      results demonstrate that the WMFT differentiated higher from lower functioning
      participants across sites; scores were uninfluenced by hand dominance or affected
      side. Women exhibited slower performance times than men. The Functional Ability
      scale (FAS) portion of the WMFT also revealed lower scores among lower
      functioning participants and women. Minimal changes were observed after repeating
      the WMFT among delayed group participants 2 weeks later. The FMA revealed similar
      results when the total group was divided into higher and lower functional levels
      at its midpoint score of 33. The WMFT discriminates higher from lower functioning
      participants tested across research sites. Comparable findings using the FMA
      support the criterion validity of the WMFT.

PMID- 16093412
TI  - A new device for experimental modeling of central nervous system injuries.
AB  - This article introduces a new device for inducing central nerve system injuries
      in experimental studies with animal models. The construction of the device is
      based on a commercially available servo-drive system incorporating the latest
      instrumentation technology and software developed in house to control the motion
      profile of the injury bit. The software, which is available upon request from the
      author, was designed such that the user can set the mechanical properties of the
      motion. For the purpose of quality control, tests were described and performed to
      assess the ability of the device to reproduce the prescribed motion when operated
      repetitively under the same set of parameters. Experiments were then conducted on
      animals to injure mouse brain and rat spinal cord. Following the injuries, in
      vivo magnetic resonance imaging was performed on the animals to depict the
      pathologies of the resulting injuries in the corresponding neuronal tissues. Rat
      spinal cords injured mildly and severely were followed longitudinally for up to
      28 days postinjury. The neurobehaviors of the animals evaluated using locomotor
      rating scores indicated the ability of the device to produce repeatable graded
      injuries.

PMID- 16093411
TI  - An auditory brain-computer interface based on the self-regulation of slow
      cortical potentials.
AB  - OBJECTIVES: Communication support for severely paralyzed patients with visual
      impairment is needed. Therefore, the feasibility of a brain-computer interface
      (BCI) using auditory stimuli alone, based on the self-regulation of slow cortical
      potentials (SCPs), was investigated. METHODS: Auditory stimuli were used for task
      and feedback presentation in an SCP self-regulation paradigm. Voluntarily
      produced SCP responses and measures of communication performance were compared
      between 3 groups (total of N = 59) of visual, auditory, and cross-modal visual
      auditory modality. Electroencephalogram recordings and training from Cz-mastoids
      were carried out on 3 consecutive sessions. Data of 1500 trials per subject were
      collected. RESULTS: Best performance was achieved for the visual, followed by the
      auditory condition. The performance deficit of the auditory condition was partly
      due to decreased self-produced positivity. Larger SCP response variability also
      accounted for lower performance of the auditory condition. Cross-modally
      presented stimuli did not lead to significant learning and control of SCP.
      CONCLUSIONS: Brain-computer communication using auditory stimuli only is
      possible. Smaller cortical positivity achieved in the auditory condition, as
      compared to the visual condition, may be a consequence of increased selective
      attention to simultaneously presented auditory stimuli. To optimize performance,
      auditory stimuli characteristics may have to be adapted. Other suggestions for
      enhancement of communication performance with auditory stimuli are discussed.

PMID- 16093413
TI  - A survey of goal-setting methods used in rehabilitation.
AB  - OBJECTIVES: This survey provides a description of the goal-setting methods that
      are currently being used in community and inpatient rehabilitation centers across
      the United Kingdom. Given current policy, emphasis was placed on finding out how
      much patient involvement in the goal-setting process exists, concentrating on how
      such involvement may be facilitated. DESIGN: A postal survey design was used to
      access a large sample size over a broad geographical area. The questionnaire was
      piloted at a British Society for Rehabilitation Medicine (BSRM) meeting;
      subsequently, some response categories were expanded. The questionnaire was
      approved by the BSRM Research and Clinical Standards committee. Questionnaires
      were coded to track responses from individuals. The received data were anonymized
      and analyzed using a statistics package for social science (SPSS) database.
      Subjects. Members of the BSRM were selected for this survey because this
      represents one of the most comprehensive listings of rehabilitation services in
      the United Kingdom. RESULTS: The survey had a 60% response rate. A problem
      orientated approach to goal setting was most commonly reported, with
      rehabilitation teams defining, formulating, and evaluating the goals. Patients
      were supplied with limited information about goal setting during their
      rehabilitation admission, although 60% of respondents reported giving patients a
      copy of their goals. Thirty percent of respondents used goals as a measure of
      rehabilitation effectiveness. Standardized goal-setting measures were not
      commonly used. CONCLUSION: These data demonstrate that individual disciplines
      tend to discuss potential goals with their patients during treatment sessions and
      then formulate goals on the basis of the discussion. There is scope to develop
      and refine the approach to goal setting so the patients have more opportunities
      to engage in the goal-setting process.

PMID- 16093414
TI  - Assessment of the quality of life of mothers of children with cerebral palsy
      (primary caregivers).
AB  - OBJECTIVES: To evaluate the quality of life and psychological status in mothers
      of children with cerebral palsy (MCCPs) and to assess their relation with regard
      to the degree of their child's disability. DESIGN: Face-to-face interviews with
      MCCPs have been performed. A prospective, case control study. SETTING: Physical
      therapy and rehabilitation training and research hospital. Subjects. 46 MCCPs and
      the mothers of 46 healthy children. MAIN OUTCOME MEASURE: Notthingam Health
      Profile-1, Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI)
      scores in MCCPs and the mothers of healthy children. Gross Motor Function
      Classification System (GMFCS) was used for the children with cerebral palsy.
      RESULTS: A significantly worsened (P = 0.001) quality of life was observed in
      MCCPs compared to the mothers of healthy children. BDI scores of the MCCPs were
      significantly higher than the mothers in the control group (P = 0.000). There
      were no significant differences in BAI scores between MCCPs and control mothers
      (P > 0.05). A positive correlation between the quality of life and BDI scores was
      noted in MCCPs (P = 0.000, r = 0.57), and no correlation was detected between the
      quality of life in MCCPs and the GMFCS levels of children with cerebral palsy (r
      = 0.012, P = 0.95). CONCLUSION: The quality of life in MCCPs is significantly
      lower than that of control mothers. Also, although the BAI scores were not
      significantly different between the groups, the BDI scores were poorer in MCCPs
      compared to those the control group.

PMID- 16093415
TI  - Individual factors in constraint-induced movement therapy after stroke.
AB  - OBJECTIVES: Constraint-induced movement therapy (CIMT) has been shown to be
      effective in chronic stroke patients. It is worthwhile to investigate the
      influence of individual factors for two reasons: to find out whether they
      influence outcome and to see whether they support the theory underlying CIMT.
      METHODS: A group of 26 patients were treated with CIMT and followed over 6
      months. In total, 14 individual factors were identified. Patients were assessed
      with 6 tests, including 2 commonly used after stroke (Frenchay Arm Test, 9 Hole
      Peg Test). RESULTS: There were individual differences, but as a group, patients
      improved after therapy. There were no individual factors that influenced
      improvement in more than one test. CONCLUSIONS: CIMT is an effective therapy in
      patients with moderate impairment after stroke, also in tests commonly used in
      stroke rehabilitation. Factors that could have expected to make a difference on
      the basis of the theory behind CIMT (e.g., time since stroke, previous therapy,
      sensory deficit) did not influence results. Patients with hemorrhagic lesions and
      those with a high level of performance (Motor Activity Log > 2.5) profit as well.
      Pairwise therapy is as effective as individual therapy.

PMID- 16093416
TI  - Coordination of hemiparetic locomotion after stroke rehabilitation.
AB  - OBJECTIVES: Determine whether a rehabilitation program targeting functional motor
      recovery of persons with poststroke hemiparesis improved motor coordination.
      METHODS: A subgroup of 20 persons with poststroke hemiparesis (n = 11 in
      intervention and n =9 in control group) was investigated from within a larger
      randomized controlled single-blind clinical trial of 100 patients. Motor
      coordination was measured using a pedaling task, and subjects in the intervention
      group pedaled during an intensive broad-based home exercise program that targeted
      flexibility, strength, balance, and endurance. Coordination variables based on
      paretic leg pedal forces and EMG of 4 thigh muscles were measured while pedaling
      pre- and postintervention. RESULTS: Despite extensive pedaling practice, up to 30
      half-hour sessions that were progressively more intense, there was no effect (P >
      0.05) of the intervention on percent of total work done by the paretic leg,
      quantitative measures of EMG, or pedaling speed. However, walking speed was
      improved and pedaling and walking faster were associated after the intervention.
      CONCLUSIONS: There is no evidence of improved locomotor coordination
      postintervention. The increased walking and pedaling speed was likely achieved by
      a more proficient use of the same impaired pattern without EMG timing changes,
      likely because of increased strength and endurance postintervention. A more task
      specific intervention may be required to improve coordination, consistent with
      principles of use-dependent plasticity.

PMID- 16093417
TI  - Underappreciated statin-induced myopathic weakness causes disability.
AB  - INTRODUCTION: Myopathic syndromes induced by 3-hydroxy-3-methylglutaryl coenzyme
      A (HMG-CoA) reductase inhibitors (statins) include muscle complaints, myalgia,
      myositis, and rhabdomyolysis. No prospective study of statins, however, included
      tests of strength, so the incidence of weakness, with or without muscle symptoms
      and elevated enzymes, is unknown, and perhaps overlooked. METHODS: From a
      convenience sample of patients referred to an outpatient neurorehabilitation
      clinic over the course of 1 year, 8 patients with hemiparetic stroke and 10
      patients with other presumed neurologic diseases presented with new difficulty
      walking by 3 to 12 months after starting one of 3 statins. They reported no
      myalgias, exercise-induced aches, or weakness. Examination revealed proximal
      paresis graded 4/5 on the unaffected side in the hemiparetic patients and
      symmetrical bilateral proximal limb and neck flexor weakness graded 4/5 in the
      others. They stood up with difficulty and walked with bilateral hip drop and
      imbalance on turns. RESULTS: Laboratory tests did not reveal myositis or other
      causes for paresis. No improvement in strength or mobility was found 6 weeks
      after initiating resistance exercises. The statin agent was stopped. By 3 months
      off statin, all recovered 5/5 proximal strength. Walking improved, and they arose
      from a chair without pushing off with their arms. DISCUSSION: Serial manual
      muscle testing after initiating a statin may detect a reversible cause of
      disability. A genetic predisposition to statin-induced myopathic proximal
      weakness with normal creatine kinase is consistent with a continuum of previously
      reported symptoms and signs but may be underappreciated.

PMID- 16093418
TI  - Epithelial cells and their neighbors. II. New perspectives on efferent signaling
      between brain, neuroendocrine cells, and gut epithelial cells.
AB  - Surface sensory enteroendocrine cells are established mucosal taste cells that
      monitor luminal contents and provide an important link in transfer of information
      from gut epithelium to the central nervous system. Recent studies now show that
      these cells can also mediate efferent signaling from the brain to the gut.
      Centrally elicited stimulation of vagal and sympathetic pathways induces release
      of melatonin, which acts at MT2 receptors to increase mucosal electrolyte
      secretion. Psychological factors as well mucosal endocrine cell hyperplasia are
      implicated in functional intestinal disorders. Central nervous influence on the
      release of transmitters from gut endocrine cells offers an exciting area of
      future gastrointestinal research with a clinical relevance.

PMID- 16093419
TI  - Gastrointestinal stem cells. II. Intestinal stem cells.
AB  - Current views of the identity, distribution, and regulation of small intestinal
      epithelial stem cells and their immediate progeny are discussed. Recent works
      implicating Wnt signaling in stem and progenitor proliferation, the involvement
      of Notch signaling in epithelial lineage specification, and the role of hedgehog
      and bone morphogenetic protein families in crypt formation are integrated. We had
      the good fortune that many of these papers came in pairs from independent groups.
      We attempt to identify points of agreement, reinterpret each in the context of
      the other, and indicate directions for continued progress.

PMID- 16093420
TI  - Two pathways for ATP release from host cells in enteropathogenic Escherichia coli
      infection.
AB  - We previously reported that enteropathogenic Escherichia coli (EPEC) infection
      triggered a large release of ATP from the host cell that was correlated with and
      dependent on EPEC-induced killing of the host cell. We noted, however, that under
      some circumstances, EPEC-induced ATP release exceeded that which could be
      accounted for on the basis of host cell killing. For example, EPEC-induced ATP
      release was potentiated by noncytotoxic agents that elevate host cell cAMP, such
      as forskolin and cholera toxin, and by exposure to hypotonic medium. These
      findings and the performance of the EPEC espF mutant led us to hypothesize that
      the CFTR plays a role in EPEC-induced ATP release that is independent of cell
      death. We report the results of experiments using specific, cell-permeable CFTR
      activators and inhibitors, as well as transfection of the CFTR into non-CFTR
      expressing cell lines, which incriminate the CFTR as a second pathway for ATP
      release from host cells. Increased ATP release via CFTR is not accompanied by an
      increase in EPEC adherence to transfected cells. The CFTR-dependent ATP release
      pathway becomes activated endogenously later in EPEC infection, and this
      activation is mediated, at least in part, by generation of extracellular
      adenosine from the breakdown of released ATP.

PMID- 16093421
TI  - Role of Na-K-2Cl cotransporter-1 in gastric secretion of nonacidic fluid and
      pepsinogen.
AB  - Na-K-2Cl cotransporter-1 (NKCC) has been detected at exceptionally high levels in
      the gastric mucosa of several species, prompting speculation that it plays
      important roles in gastric secretion. To investigate this possibility, we 1)
      immunolocalized NKCC protein in the mouse gastric mucosa, 2) compared the volume
      and composition of gastric fluid from NKCC-deficient mice and their normal
      littermates, and 3) measured acid secretion and electrogenic ion transport by
      chambered mouse gastric mucosa. NKCC was localized to the basolateral margin of
      parietal cells, mucous neck cells, and antral base cells. In NKCC-deficient mice,
      gastric secretions of Na+, K+, Cl-, fluid, and pepsinogen were markedly impaired,
      whereas secretion of acid was normal. After stimulation with forskolin or 8-bromo
      cAMP, chambered corpus mucosa vigorously secreted acid, and this was accompanied
      by an increase in transmucosal electrical current. Inhibition of NKCC with
      bumetanide reduced current to resting levels but had no effect on acid output.
      Although prominent pathways for basolateral Cl- uptake (NKCC) and apical Cl- exit
      [cystic fibrosis transmembrane conductance regulator (CFTR)] were found in antral
      base cells, no impairment in gastric secretion was detected in CFTR-deficient
      mice. Our results establish that NKCC contributes importantly to secretions of
      Na+, K+, Cl-, fluid, and pepsinogen by the gastric mucosa through a process that
      is electrogenic in character and independent of acid secretion. The probable
      source of the NKCC-dependent nonacidic electrogenic fluid secretion is the
      parietal cell. The observed dependence of pepsinogen secretion on NKCC supports
      the concept that a nonacidic secretory stream elaborated from parietal cells
      facilitates flushing of the proenzyme from the gastric gland lumen.

PMID- 16093422
TI  - Upregulation of cyclooxygenase-2 and thromboxane A2 production mediate the action
      of tumor necrosis factor-alpha in isolated rat myenteric ganglia.
AB  - Intact myenteric ganglia from 4- to 10-day-old rats were isolated from the small
      intestine. The preparations were cultured overnight, and drugs were applied
      within this time frame (20 h). Whole cell patch-clamp technique was used to
      measure basal membrane potential and carbachol-induced depolarization at neurons
      within these ganglia. Pretreatment with TNF-alpha (100 ng/ml) hyperpolarized the
      membrane (from -31.0 +/- 2.7 mV under control conditions to -61.2 +/- 3.2 mV in
      the presence of the cytokine) and potentiated the depolarization induced by
      carbachol (from 5.2 +/- 0.7 mV under control conditions to 27.5 +/- 2.0 mV in the
      presence of the cytokine). These effects were mimicked by carbocyclic thromboxane
      A2 (10(-6) mol/l), a stable thromboxane A2 agonist. The TNF-alpha action was
      inhibited by 1-benzylimidazole (2 x 10(-4) mol/l), a thromboxane synthase
      inhibitor, and BAY U 3405 (5 x 10(-4) mol/l), an inhibitor of thromboxane
      receptors. Measurements of thromboxane production in the supernatant of the
      culture revealed an increased concentration of thromboxane B2, the stable
      metabolite of thromboxane A2, after exposure to TNF-alpha. Immuncytochemical
      staining for cyclooxygenase-2 (COX-2) and the neuronal marker microtubule
      associating protein-2 revealed an upregulation of COX-2 in myenteric neurons
      after exposure to the cytokine. These results demonstrate the involvement of COX
      2 and the subsequent production of thromboxane A2 in the presence of TNF-alpha.

PMID- 16093423
TI  - Angiotensin receptors and actions in guinea pig enteric nervous system.
AB  - Actions of ANG II on electrical and synaptic behavior of enteric neurons in the
      guinea pig small intestine were studied. Exposure to ANG II depolarized the
      membrane potential and elevated neuronal excitability. The number of responding
      neurons was small, with responses to ANG II in 32% of submucosal neurons and 25%
      of myenteric neurons. Hyperpolarizing responses were evoked by ANG II in 45% of
      the neurons. The hyperpolarizing responses were suppressed by alpha2
      noradrenergic receptor antagonists, which suggested that the hyperpolarizing
      responses reflected stimulation of norepinephrine release from sympathetic
      neurons. Exposure to ANG II enhanced the amplitude and prolonged the duration of
      noradrenergic inhibitory postsynaptic potentials and suppressed the amplitude of
      both fast and slow excitatory postsynaptic potentials. The selective ANG II(1)
      receptor (AT1R) antagonists, ZD-7115 and losartan, but not a selective AT2R
      antagonist (PD-123319), suppressed the actions of ANG II. Western blot analysis
      and RT-PCR confirmed expression of AT1R protein and the mRNA transcript for the
      AT1R in the enteric nervous system. No expression of AT2R protein or mRNA was
      found. Immunoreactivity for AT1R was expressed by the majority of neurons in the
      gastric antrum and small and large intestine. AT1R immunoreactivity was
      coexpressed with calbindin, choline acetyltransferase, calretinin, neuropeptide
      Y, and nitric oxide synthase in subpopulations of neurons. The results suggest
      that formation of ANG II might have paracrine-like actions in the enteric nervous
      system, which include alterations in neuronal excitability and facilitated
      release of norepinephrine from sympathetic postganglionic axons. The enhanced
      presence of norepinephrine is expected to suppress fast and slow excitatory
      neurotransmission in the enteric microcircuits and to suppress neurogenic mucosal
      secretion.

PMID- 16093424
TI  - More than just a barrier: urothelium as a drug target for urinary bladder pain.
AB  - Although the urinary bladder urothelium has classically been thought of as a
      passive barrier to ions/solutes, a number of novel properties have been recently
      attributed to these cells. Studies have revealed that the urothelium is involved
      in sensory mechanisms (i.e., ability to express a number of sensor molecules or
      respond to thermal, mechanical, and chemical stimuli) and can release chemical
      mediators. Localization of afferent nerves next to the urothelium suggests these
      cells may be targets for transmitters released from bladder nerves or that
      chemicals released by urothelial cells may alter afferent excitability. Taken
      together, these and other findings highlighted in this review suggest a sensory
      function for the urothelium. Elucidation of mechanisms impacting on urothelial
      function may provide insights into the pathology of bladder dysfunction.

PMID- 16093425
TI  - Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal
      diseases.
AB  - Renal epoxygenase metabolites are involved in blood flow regulation and long-term
      blood pressure control. One feature of renal and cardiovascular diseases is the
      inability of the kidney to properly increase epoxyeicosatrienoic acid (EET)
      levels. Others (Busse R, Edwards G, Feletou M, Fleming I, Vanhoutte PM, and
      Weston AH. Trends Phamacol Sci 23: 374-380, 2002; Campbell WB, Gebremedhin D,
      Pratt PF, and Harder DR. Circ Res 78: 415-423, 1996; Capdevila JH and Falck JR.
      Biochem Biophys Res Commun 285: 571-576, 2001; Roman RJ. Physiol Rev 82: 131-185,
      2002; Zeldin DC. J Biol Chem 276: 36059-36062, 2001) and we (Imig JD, Falck JR,
      Wei S, and Capdevila JH. J Vasc Res 38: 247-255, 2001; Imig JD, Zhao X, Capdevila
      JH, Morisseau C, and Hammock BD. Hypertension 39: 690-694, 2002; Zhao X, Pollock
      DM, Inscho EW, Zeldin DC, and Imig JD. Hypertension 41: 709-714, 2003; Zhao X,
      Pollock DM, Zeldin DC, and Imig JD. Hypertension 42: 775-780, 2003) have provided
      compelling evidence that cytochrome P-450-derived EETs have antihypertensive
      properties and are endothelially derived hyperpolarizing factors (EDHFs) in the
      kidney. EETs also possess anti-inflammatory actions that could protect the kidney
      vasculature from injury during renal and cardiovascular diseases. A tactic that
      has been used to increase EET levels has been inhibition of the soluble epoxide
      hydrolase enzyme. Epoxide hydrolase inhibitors have been demonstrated to be
      antihypertensive and renal protective. Thus the renal and cardiovascular
      protective actions of increasing epoxygenase levels could be translated to
      therapies for preventing end-organ damage.

PMID- 16093426
TI  - DNA damage signals facilitate osmotic stress adaptation.

PMID- 16093427
TI  - Provenance of the protective property of p21.

PMID- 16093428
TI  - Mechanical strain increases SPARC levels in podocytes: implications for
      glomerulosclerosis.
AB  - Glomerular capillary hypertension is a final common pathway to
      glomerulosclerosis. Because podocyte loss is an early event in the development of
      glomerulosclerosis, it is logical that the deleterious effects of glomerular
      capillary hypertension involve podocyte injury. Yet, the mechanisms by which
      elevated intraglomerular pressure is translated into a maladaptive podocyte
      response remain poorly understood. Secreted protein acidic and rich in cysteine
      (SPARC) is a matricellular protein activated in various disease states of the
      podocyte and accelerates renal injury, as evidenced by the milder course of
      experimental diabetic nephropathy in SPARC-null mice compared with diabetic SPARC
      wild-type mice. Accordingly, we tested the hypothesis that mechanical strain
      activates SPARC in podocytes and thus is a putative mediator of podocyte injury
      in states of intraglomerular capillary hypertension. Conditionally immortalized
      mouse podocytes were subjected to 10% cyclical stretch while nonstretched cells
      served as controls. SPARC levels were measured in whole cell lysate and cell
      media. Immunostaining was performed for SPARC in an experimental model of
      glomerular capillary hypertension. Our results demonstrate cyclical stretch of
      podocytes markedly increased SPARC levels in cell lysate, through activation of
      p38, as well as secreted SPARC. Relevance was shown by demonstrating increased
      podocyte staining for SPARC in the uninephrectomized spontaneously hypertensive
      rat. In conclusion, we have made the novel observation that mechanical forces
      characteristic of states of glomerular capillary hypertension lead to increased
      levels of SPARC in podocytes. We speculate that the increase in SPARC may be
      maladaptive and lead to a progressive reduction in podocyte number, thus fueling
      the future development of glomerulosclerosis.

PMID- 16093429
TI  - Murine double minute 2 as a therapeutic target for radiation sensitization of
      lung cancer.
AB  - Murine double minute 2 (MDM2) inhibits p53-mediated functions, which are
      essential for therapies using DNA-damaging agents. The purpose of this study was
      to determine whether MDM2 inhibition enhances the radiosensitivity of a lung
      cancer model. The effects of MDM2 inhibition on tumor vasculature were also
      studied. Transient transfection of H460 lung cancer cells and human umbilical
      vascular endothelial cells (HUVEC) with antisense oligonucleotides (ASODN)
      against MDM2 resulted in a reduced level of MDM2 and increased levels of p21 and
      p53. Clonogenic assays showed that inhibition of MDM2 greatly decreased cell
      survival following irradiation. Quantification of apoptotic cells by 7
      aminoactinomycin D staining and of senescent cells by X-gal staining showed that
      both processes were significantly increased in H460 cells treated with MDM2
      specific ASODN and radiation. H460 xenografts that were treated with MDM2 ASODN
      plus radiotherapy also showed significant growth delay (P < 0.001) and increased
      apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling
      staining. HUVECs transfected with MDM2-specific ASODN showed impaired viability
      and migration with decreased tube formation. Doppler studies showed that tumor
      blood flow was compromised when H460 xenografts were treated with MDM2-specific
      ASODN and radiation. A combination of radiotherapy and inhibition of MDM2 through
      the antisense approach results in improved tumor control in the H460 lung cancer
      model. This implies that a similar strategy should be investigated among patients
      with locally advanced lung cancer, receiving thoracic radiotherapy.

PMID- 16093430
TI  - Integrin-linked kinase is a potential therapeutic target for anaplastic thyroid
      cancer.
AB  - We investigated integrin-linked kinase (ILK), a focal adhesion serine-threonine
      protein kinase, as a new molecular target for treating anaplastic thyroid cancer.
      ILK mediates cell growth and survival signals and is overexpressed in a number of
      cancers. Therefore, we hypothesized that inhibition of ILK leads to growth arrest
      and apoptosis of thyroid cancer cells. According to Western blotting, the level
      of ILK protein was highly expressed in one papillary (NPA187) and four of five
      (Hth74, DRO, ARO, KAT4, and K4) anaplastic thyroid cancer cell lines.
      Immunohistochemical analysis of a human tissue microarray revealed that ILK was
      highly expressed in anaplastic thyroid cancer but not in normal human thyroid
      tissue. Treating thyroid cancer cell lines with a new ILK inhibitor, QLT0267,
      inhibited epidermal growth factor-induced phosphorylation of AKT, inhibited cell
      growth, and induced apoptosis in the NPA187, DRO, and K4 cell lines. QLT0267 also
      inhibited the kinase activity of immunoprecipitated ILK in four of five cell
      lines. Tumor volumes in mice treated with QLT0267 were significantly reduced
      compared with those in untreated mice. In immunohistochemical studies, QLT0267
      suppressed phosphorylated p-AKT and angiogenesis (i.e., reduced mean vascular
      density) and induced apoptosis in both tumor cells and tumor-associated
      endothelial cells of the thyroid DRO xenografts. In summary, we found that ILK
      expression and activity were elevated in human anaplastic thyroid cancer and ILK
      inhibition led to growth arrest and apoptosis in vitro and in vivo. Our results
      provide preliminary evidence that ILK is a potential therapeutic target for
      treating anaplastic thyroid cancer.

PMID- 16093431
TI  - Competitive disruption of the tumor-promoting function of membrane type 1 matrix
      metalloproteinase/matrix metalloproteinase-14 in vivo.
AB  - Membrane type 1 matrix metalloproteinase (MT1-MMP) is a potent modulator of the
      pericellular environment and promotes tumor cell invasion and proliferation in
      many types of tumor. The activation of proMMP-2 and processing of collagen I by
      MT1-MMP have been thought to be important for its tumor-promoting function. These
      activities can be inhibited by mutant forms of MT1-MMP lacking the catalytic
      domain. However, the effect of such dominant-negative mutants has never been
      evaluated in vivo. Various mutants lacking the catalytic domain (dCAT) were
      prepared and confirmed to inhibit MT1-MMP activity in human fibrosarcoma HT1080
      cells, and tumor cells expressing these mutants were implanted s.c. into nude
      mice to monitor tumor formation. Only the membrane-anchored form of a dCAT
      construct through the transmembrane domain [dCAT(1)] showed potent antitumor
      activity not only in HT1080 cells but also in gastric carcinoma MKN28 and MKN45
      cells expressing MT1-MMP. A soluble form of dCAT lacking the transmembrane domain
      did not show such activity. The expression of dCAT(1) in MKN28 or MKN45 further
      prevented the metastatic spread of tumor cells into the peritoneal cavity;
      however, dCAT(1) showed no effect against TMK-1, another gastric carcinoma cell
      line expressing no MT1-MMP. It is of note that the tumorigenicity of TMK-1 cells
      enhanced by MT1-MMP overexpression was, in turn, canceled by the additional
      expression of dCAT(1). Thus, MT1-MMP expressed in tumor cells seems to play a
      pivotal role in tumor growth in mice. The results also suggest new possibilities
      to abrogate the tumor-promoting function of MT1-MMP other than the conventional
      protease inhibitor-based approach.

PMID- 16093432
TI  - T315I-mutated Bcr-Abl in chronic myeloid leukemia and imatinib: insights from a
      computational study.
AB  - The early stage of chronic myeloid leukemia is triggered by the tyrosine kinase
      Bcr-Abl. Imatinib mesylate, a selective inhibitor of Bcr-Abl, has been successful
      in chronic myeloid leukemia clinical trials, but short-lived remissions are
      usually observed in blast crisis patients. Sequencing of the BCR-ABL gene in
      relapsed patients revealed a set of mutants that mediate drug resistance.
      Previously reported work postulated that the missense T315I mutation both alters
      the three-dimensional structure of the protein binding site, thus decreasing the
      protein sensitivity for the drug, and does not feature a fundamental hydrogen
      bond that is critical for binding with imatinib. These speculations, however,
      were not supported by investigations at the molecular modeling level. Here, we
      present the results obtained from the application of molecular dynamics
      simulations to the study of the interactions between T315I Bcr-Abl and imatinib.
      For the first time, we show that, with respect to the wild-type system, the
      absence of the supposedly critical H-bond is not the only cause for the failure
      of receptor inhibition by imatinib, but also a plethora of other protein/drug
      interactions are drastically and unfavorably changed in the mutant protein.

PMID- 16093433
TI  - Hedamycin, a DNA alkylator, induces (gamma)H2AX and chromosome aberrations:
      involvement of phosphatidylinositol 3-kinase-related kinases and DNA replication
      fork movement.
AB  - Genotoxic treatments, such as UV light, camptothecin, and adozelesin, stall DNA
      replication and subsequently generate DNA strand breaks. Typically, DNA breaks
      are reflected by an increase in ataxia and Rad-related kinase (ATR)-regulated
      phosphorylation of H2AX (gammaH2AX) and require replication fork movement. This
      study examined the potential of the monofunctional DNA alkylating agent
      hedamycin, a powerful inhibitor of DNA replication, to induce DNA strand breaks,
      phosphorylated H2AX (gammaH2AX) foci, and chromosome aberrations. Hedamycin
      treatment of HCT116 carcinoma cells resulted in a rapid induction of DNA strand
      breaks accompanied by increasing H2AX phosphorylation and focalization. Unlike
      many other treatments that also stall replication, such as UV, camptothecin, and
      adozelesin, gammaH2AX formation was not suppressed in ATR-compromised cells but
      actually increased. Similarly, hedamycin induction of gammaH2AX is not dependent
      on ataxia telangiectasia mutated or DNA-protein kinase, and pretreatment of cells
      with the phosphatidylinositol 3-kinase-related kinase inhibitor caffeine did not
      substantially reduce induction of H2AX phosphorylation by hedamycin. Furthermore,
      the DNA replication inhibitor aphidicolin only modestly depressed hedamycin
      induced gammaH2AX formation, indicating that hedamycin-induced DNA double-strand
      breaks are not dependent on fork progression. In contrast, camptothecin- and
      adozelesin-induced gammaH2AX was strongly suppressed by aphidicolin. Moreover,
      after 24 hours following a short-term hedamycin treatment, cells displayed high
      levels of breaks in interphase nuclear DNA and misjoined chromosomes in metaphase
      cells. Finally, focalization of a tightly bound form of Ku80 was observed in
      interphase cells, consistent with the subsequent appearance of chromosomal
      aberrations via abnormal nonhomologous end joining. Overall, this study has
      revealed a disparate type of DNA damage response to stalled replication induced
      by a bulky DNA adduct inducer, hedamycin, that seems not to be highly dependent
      on ATR or DNA replication.

PMID- 16093434
TI  - Temporal quantitation of mutant Kit tyrosine kinase signaling attenuated by a
      novel thiophene kinase inhibitor OSI-930.
AB  - OSI-930, a potent thiophene inhibitor of the Kit, KDR, and platelet-derived
      growth factor receptor tyrosine kinases, was used to selectively inhibit tyrosine
      phosphorylation downstream of juxtamembrane mutant Kit in the mast cell leukemia
      line HMC-1. Inhibition of Kit kinase activity resulted in a rapid
      dephosphorylation of Kit and inhibition of the downstream signaling pathways.
      Attenuation of Ras-Raf-Erk (phospho-Erk, phospho-p38), phosphatidyl inositol-3'
      kinase (phospho-p85, phospho-Akt, phospho-S6), and signal transducers and
      activators of transcription signaling pathways (phospho-STAT3/5/6) were measured
      by affinity liquid chromatography tandem mass spectrometry, by immunoblot, and by
      tissue microarrays of fixed cell pellets. To more globally define additional
      components of Kit signaling temporally altered by kinase inhibition, a novel
      multiplex quantitative isobaric peptide labeling approach was used. This approach
      allowed clustering of proteins by temporal expression patterns. Kit kinase, which
      dephosphorylates rapidly upon kinase inhibition, was shown to regulate both Shp-1
      and BDP-1 tyrosine phosphatases and the phosphatase-interacting protein PSTPIP2.
      Interactions with SH2 domain adapters [growth factor receptor binding protein 2
      (Grb2), Cbl, Slp-76] and SH3 domain adapters (HS1, cortactin, CD2BP3) were
      attenuated by inhibition of Kit kinase activity. Functional crosstalk between Kit
      and the non-receptor tyrosine kinases Fes/Fps, Fer, Btk, and Syk was observed.
      Inhibition of Kit modulated phosphorylation-dependent interactions with pathways
      controlling focal adhesion (paxillin, leupaxin, p130CAS, FAK1, the Src family
      kinase Lyn, Wasp, Fhl-3, G25K, Ack-1, Nap1, SH3P12/ponsin) and septin-actin
      complexes (NEDD5, cdc11, actin). The combined use of isobaric protein
      quantitation and expression clustering, immunoblot, and tissue microarray
      strategies allowed temporal measurement signaling pathways modulated by mutant
      Kit inhibition in a model of mast cell leukemia.

PMID- 16093435
TI  - Validation of in vivo pharmacodynamic activity of a novel PDGF receptor tyrosine
      kinase inhibitor using immunohistochemistry and quantitative image analysis.
AB  - With the advent of agents directed against specific molecular targets in drug
      discovery, it has become imperative to show a compound's cellular impact on the
      intended biomolecule in vivo. The objective of the present study was to determine
      if we could develop an assay to validate the in vivo effects of a compound.
      Hence, we investigated the in vivo pharmacodynamic activity of JNJ-10198409, a
      relatively selective inhibitor of platelet-derived growth factor receptor
      tyrosine kinase (PDGF-RTK), in tumor tissues after administering the compound
      orally in a nude mouse xenograft model of human LoVo colon cancer. We developed a
      novel assay to quantify the in vivo anti-PDGF-RTK activity of the inhibitor in
      tumor tissue by determining the phosphorylation status of phospholipase Cgamma1
      (PLCgamma1), a key downstream cellular molecule in the PDGF-RTK signaling
      cascade. We used two antibodies, one specific for the total (phosphorylated and
      unphosphorylated forms) PLCgamma1 (pan-PLCgamma1) and the other, specific for
      phosphorylated form of PLCgamma1 (ph-PLCgamma1) to immunohistochemically detect
      their expression in tumor tissues. Computer-assisted image analysis was then used
      to directly compare the ratio of ph-PLCgamma1 to pan-PLCgamma1 immunolabeling
      intensities in serial sections (5 mum) of tumors obtained from vehicle- and JNJ
      10198409-treated tumor-bearing mice. Our data showed statistically significant,
      dose-dependent differences in the ph-PLC/pan-PLC ratio among the four treatment
      groups (vehicle, 25, 50, and 100 mg/kg b.i.d.). These results confirmed this
      compound's ability to suppress PDGF-RTK downstream signaling in tumor tissues in
      vivo. In addition to this specific application of this in vivo validation
      approach to those targets that use PLCgamma as a downstream signaling partner,
      these methods may also benefit other drug discovery targets.

PMID- 16093436
TI  - The immunocytokine scFv23/TNF sensitizes HER-2/neu-overexpressing SKBR-3 cells to
      tumor necrosis factor (TNF) via up-regulation of TNF receptor-1.
AB  - Overexpression of HER-2/neu confers cellular resistance to tumor necrosis factor
      (TNF)-mediated cytotoxicity to SKBR-3 breast cancer cell lines. To understand the
      correlation between HER-2/neu expression and TNF resistance, we examined the
      unique signaling pathways associated with the cytotoxic effects of the
      immunocytokine scFv23/TNF, recombinant single-chain antibody fusion constructs
      containing TNF and targeting HER-2/neu, in TNF-resistant SKBR-3-LP cells. We
      found that treatment of HER-2/neu-overexpressing SKBR-3-LP cells with scFv23/TNF
      resulted in a 5- to 7-fold higher level of TNF receptor-1 expression 48 hours
      after exposure. In addition, treatment of SKBR-3-LP cells with scFv23/TNF
      resulted in down-regulation of Akt phosphorylation and induced apoptosis through
      cleavage of caspase-8, caspase-3, and poly(ADP-ribose) polymerase. ScFv23/TNF
      induced cytotoxicity was inhibited by blocking of the binding of the TNF
      component of scFv23/TNF to TNF receptor-1 and was dependent on activation of
      caspase-8 and caspase-3. These results indicate that the immunocytokine
      scFv23/TNF sensitizes TNF-resistant HER-2/neu-overexpressing SKBR-3-LP cells to
      TNF-induced apoptosis via the overexpression of TNF receptor-1 and suggest that
      the overexpression of TNF receptor-1 plays a crucial role in TNF sensitivity in
      HER-2/neu-overexpressing cancer cells. ScFv23/TNF targeting the HER-2/neu may be
      an effective cytotoxic agent against HER-2/neu-overexpressing cancer cells, which
      are inherently resistant to TNF.

PMID- 16093437
TI  - Inhibition of insulin-like growth factor-I receptor (IGF-IR) signaling and tumor
      cell growth by a fully human neutralizing anti-IGF-IR antibody.
AB  - Insulin-like growth factor-I receptor (IGF-IR) plays an important role in tumor
      cell growth and survival. On ligand stimulation, IGF-IR, a receptor tyrosine
      kinase, phosphorylates tyrosine residues on two major substrates, IRS-1 and Shc,
      which subsequently signal through the Ras/mitogen-activated protein kinase and
      phosphatidylinositol 3-kinase/AKT pathways. Here, we describe the
      characterization of a fully human anti-IGF-IR monoclonal antibody 19D12 that
      inhibits IGF binding and autophosphorylation of both IGF-IR/IGF-IR homodimers and
      IGF-IR/insulin receptor heterodimers. 19D12 does not recognize insulin receptor
      homodimers. In addition to inhibiting IGF-IR autophosphorylation, 19D12 also
      inhibits IRS-1 phosphorylation and activation of the major downstream signaling
      molecules AKT and extracellular signal-regulated kinase 1/2. Furthermore, the
      antibody down-regulates the total IGF-IR protein level and can exhibit antibody
      dependent cellular cytotoxicity activity against a non-small cell adenocarcinoma
      cell line in vitro in the presence of isolated human natural killer cells. 19D12
      binds tightly to the receptor, with an affinity of 3.8 pmol/L as measured by
      KinExA. In cell culture, 19D12 inhibits proliferation and soft agar growth of
      various tumor cell lines. In vivo, 19D12 inhibits the tumor growth of a very
      aggressive human ovarian tumor xenograft model A2780. These data support the
      development of this anti-IGF-IR monoclonal antibody as a promising anticancer
      agent.

PMID- 16093438
TI  - Histone deacetylase inhibitors induced caspase-independent apoptosis in human
      pancreatic adenocarcinoma cell lines.
AB  - The antitumor activity of the histone deacetylase inhibitors was tested in three
      well-characterized pancreatic adenocarcinoma cell lines, IMIM-PC-1, IMIM-PC-2,
      and RWP-1. These cell lines have been previously characterized in terms of their
      origin, the status of relevant molecular markers for this kind of tumor,
      resistance to other antineoplastic drugs, and expression of differentiation
      markers. In this study, we report that histone deacetylase inhibitors induce
      apoptosis in pancreatic cancer cell lines, independently of their intrinsic
      resistance to conventional antineoplastic agents. The histone deacetylase
      inhibitor-induced apoptosis is due to a serine protease-dependent and caspase
      independent mechanism. Initially, histone deacetylase inhibitors increase Bax
      protein levels without affecting Bcl-2 levels. Consequently, the apoptosis
      inducing factor (AIF) and Omi/HtrA2 are released from the mitochondria, with the
      subsequent induction of the apoptotic program. These phenomena require AIF
      relocalization into the nuclei to induce DNA fragmentation and a serine protease
      activity of Omi/HtrA2. These data, together with previous results from other
      cellular models bearing the multidrug resistance phenotype, suggest a possible
      role of the histone deacetylase inhibitors as antineoplastic agents for the
      treatment of human pancreatic adenocarcinoma.

PMID- 16093439
TI  - Cell cycle checkpoint signaling involved in histone deacetylase inhibition and
      radiation-induced cell death.
AB  - In breast cancer, radiation has a central role in the treatment of brain
      metastasis, although tumor sensitivity might be limited. The tumor cell defense
      response to ionizing radiation involves activation of cell cycle checkpoint
      signaling. Histone deacetylase (HDAC) inhibitors, agents that cause
      hyperacetylation of histone proteins and thereby aberrations in the chromatin
      structure, may also override the DNA damage defense response and facilitate the
      radiation-induced mitotic cell death. In experimental metastasis models, the
      human breast carcinoma cell line MA-11 invariably disseminates to the central
      nervous system. We compared profiles of in vitro MA-11 cell cycle response to
      ionizing radiation and HDAC inhibition. After radiation exposure, the G2-M phase
      accumulation and the preceding repression of the G2 phase regulatory factors Polo
      like kinase-1 and cyclin B1 required intact G2 checkpoint signaling through the
      checkpoint kinase CHK1, whereas the similar phenotypic changes observed with HDAC
      inhibition did not. MA-11 cells did not show radiation-induced expression of the
      G1 cell cycle inhibitor p21, indicative of a defective G1 checkpoint and
      consistent with a point mutation detected in the tumor suppressor TP53 gene.
      Increase in the p21 level, however, was observed with HDAC inhibition. Following
      pretreatment with the HDAC inhibitor, the efficiency of clonogenic regrowth after
      irradiation was reduced, which is in accordance with the concept of increased
      probability of mitotic cell death when the chromatin structure is disrupted.
      Among molecular cell cycle-targeted drugs currently in the pipeline for testing
      in early-phase clinical trials, HDAC inhibitors may have therapeutic potential as
      radiosensitizers.

PMID- 16093440
TI  - Selenium disrupts estrogen receptor (alpha) signaling and potentiates tamoxifen
      antagonism in endometrial cancer cells and tamoxifen-resistant breast cancer
      cells.
AB  - Tamoxifen, a selective estrogen receptor (ER) modulator, is the most widely
      prescribed hormonal therapy treatment for breast cancer. Despite the benefits of
      tamoxifen therapy, almost all tamoxifen-responsive breast cancer patients develop
      resistance to therapy. In addition, tamoxifen displays estrogen-like effects in
      the endometrium increasing the incidence of endometrial cancer. New therapeutic
      strategies are needed to circumvent tamoxifen resistance in breast cancer as well
      as tamoxifen toxicity in endometrium. Organic selenium compounds are highly
      effective chemopreventive agents with well-documented benefits in reducing total
      cancer incidence and mortality rates for a number of cancers. The present study
      shows that the organic selenium compound methylseleninic acid (MSA, 2.5
      micromol/L) can potentiate growth inhibition of 4-hydroxytamoxifen (10(-7) mol/L)
      in tamoxifen-sensitive MCF-7 and T47D breast cancer cell lines. Remarkably, in
      tamoxifen-resistant MCF-7-LCC2 and MCF7-H2Delta16 breast cancer cell lines and
      endometrial-derived HEC1A and Ishikawa cells, coincubation of 4-hydroxytamoxifen
      with MSA resulted in a marked growth inhibition that was substantially greater
      than MSA alone. Growth inhibition by MSA and MSA + 4-hydroxytamoxifen in all cell
      lines was preceded by a specific decrease in ER(alpha) mRNA and protein without
      an effect on ER(beta) levels. Estradiol and 4-hydroxytamoxifen induction of
      endogenous ER-dependent gene expression (pS2 and c-myc) as well as ER-dependent
      reporter gene expression (ERE(2)e1b-luciferase) was also attenuated by MSA in all
      cell lines before effect on growth inhibition. Taken together, these data
      strongly suggest that specific decrease in ER(alpha) levels by MSA is required
      for both MSA potentiation of the growth inhibitory effects of 4-hydroxytamoxifen
      and resensitization of tamoxifen-resistant cell lines.

PMID- 16093441
TI  - Mitochondria are the primary target in isothiocyanate-induced apoptosis in human
      bladder cancer cells.
AB  - Many isothiocysanates (ITC) are promising cancer-preventive agents, and induction
      of apoptosis is one of their underlying mechanisms of action. We recently found
      that caspase-9 was preferentially activated over other initiator caspases in
      human bladder cancer UM-UC-3 cells. We report here that caspase-9 activation is
      the major step leading to ITC-induced apoptosis in this cell line. More
      importantly, our results show that caspase-9 activation by the ITCs may result
      primarily from mitochondrial damage. Four common naturally occurring ITCs were
      studied, including allyl ITC, benzyl ITC (BITC), phenethyl ITC (PEITC), and
      sulforaphane. BITC and PEITC showed more potent mitochondria-damaging ability
      than the other two ITCs, correlating well with their stronger apoptosis-inducing
      potentials. Furthermore, BITC and PEITC damaged both the outer and inner
      mitochondrial membranes. Use of isolated mitochondria allowed us to establish
      that ITCs, and more importantly their major intracellular derivatives
      (glutathione conjugates) at concentrations that are readily achievable in cells,
      damage mitochondria, leading to the collapse of mitochondrial trans-membrane
      potential and release of cytochrome c. The mitochondria-damaging potencies of the
      ITCs correlate well with their lipophilicities. Bcl-2 family members are known to
      influence the stability of mitochondrial membrane. Our results show that the ITCs
      caused phosphorylation of Bcl-2, induced mitochondrial translocation of Bak, and
      disrupted the association of Bcl-xl with both Bak and Bax in mitochondrial
      membrane, indicating that ITC-induced mitochondrial damage results at least in
      part from modulation of select Bcl-2 family members.

PMID- 16093442
TI  - The antiproliferative agent MLN944 preferentially inhibits transcription.
AB  - MLN944 is a novel compound currently being codeveloped by Millennium
      Pharmaceuticals and Xenova Ltd. as a cancer therapeutic and is in a phase I
      clinical trial for solid tumors. Although MLN944 was originally proposed to
      function as a topoisomerase I and II inhibitor, more recent data has shown that
      it is a DNA-intercalating agent that does not inhibit the catalytic activity of
      topoisomerase I or II. We show here that MLN944 inhibits incorporation of
      radiolabeled precursors into RNA preferentially over incorporation into DNA and
      protein in HCT116 and H460 cells. To determine if MLN944 inhibits transcription,
      a human RNA polymerase II in vitro transcription system was used. MLN944
      inhibited initiation when added before or after the formation of preinitiation
      complexes and inhibited elongation at higher concentrations. The preferential
      inhibition of initiation differentiates MLN944 from actinomycin D, which more
      strongly inhibits elongation. Transcription of all RNA polymerases was inhibited
      in nuclei isolated from HeLa cells treated with low concentrations of MLN944. Our
      data are consistent with transcription as the target of the potent cytotoxic
      effects of MLN944.

PMID- 16093443
TI  - Increased expression of the large subunit of ribonucleotide reductase is involved
      in resistance to gemcitabine in human mammary adenocarcinoma cells.
AB  - Resistance to cytotoxic nucleoside analogues is a major problem in cancer
      treatment. The cellular mechanisms involved in this phenomenon have been studied
      for several years, and some factors have been identified. However, this
      resistance seems to be multifactorial and more studies are needed to gain better
      insight into this domain. For this purpose, we developed a gemcitabine-resistant
      cell line (MCF7 1K) from the human mammary adenocarcinoma MCF7 strain by
      prolonged exposure to gemcitabine in vitro. MCF7 1K cells are highly resistant to
      gemcitabine (533-fold) and cross-resistance is observed with araC (47-fold),
      triapine (14-fold), and hydroxyurea (6.7-fold). Quantitative real-time reverse
      transcription-PCR and Western blot analysis showed an increase in the gene and
      protein expression of the large subunit of ribonucleotide reductase, R1.
      Ribonucleotide reductase activity was also significantly increased in the
      gemcitabine-resistant cells. Study of genomic DNA showed 12-fold increase in R1
      gene dosage in MCF7 1K cells. In contrast, the gene and protein expression of the
      small subunit of ribonucleotide reductase, R2, were not modified in this cell
      line. These results show that gemcitabine resistance can be associated with
      genetic modifications of target genes in malignant cells, and suggest that the
      large subunit of human ribonucleotide reductase is involved in the cellular
      response to gemcitabine.

PMID- 16093444
TI  - Pristimerin induces caspase-dependent apoptosis in MDA-MB-231 cells via direct
      effects on mitochondria.
AB  - Pristimerin, a naturally occurring triterpenoid, has been shown to cause
      cytotoxicity in several cancer cell lines. However, the mechanism for the
      cytotoxic effect of pristimerin was never explored. In the present study, human
      breast cancer MDA-MB-231 cells treated with pristimerin (1 and 3 micromol/L)
      showed rapid induction of apoptosis, as indicated by caspase activation, DNA
      fragmentation, and morphologic changes. Pretreatment of a pan-caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk) completely
      prevented pristimerin-induced apoptosis. Treatment of tumor cells with
      pristimerin resulted in a rapid release of cytochrome c from mitochondria, which
      preceded caspase activation and the decrease of mitochondrial membrane potential.
      In addition, neither benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone nor
      permeability transition pore inhibitor cyclosporin A markedly prevented
      pristimerin-induced mitochondrial cytochrome c release. Pristimerin did not
      significantly alter the protein level of Bcl-2 family members (Bcl-2, Bcl-X(L),
      and Bax), nor did it induce Bax translocation. Moreover, Bcl-2 overexpression
      fails to prevent pristimerin-induced apoptosis. The generation of reactive oxygen
      species in MDA-MB-231 cells was also not affected by pristimerin. In a cell-free
      system, pristimerin induced cytochrome c release from isolated mitochondria.
      Taken together, these results suggested that pristimerin is a novel mitochondria
      targeted compound and may be further evaluated as a chemotherapeutic agent for
      human cancer.

PMID- 16093445
TI  - Septic shock after medical abortions with mifepristone (Mifeprex, RU 486) and
      misoprostol.

PMID- 16093446
TI  - Mechanisms and fetal origins of kidney disease.

PMID- 16093447
TI  - Thrombotic microangiopathy: the next big hurdle for xenotransplantation.

PMID- 16093448
TI  - Molecular biology of hereditary diabetes insipidus.
AB  - The identification, characterization, and mutational analysis of three different
      genes-the arginine vasopressin gene (AVP), the arginine vasopressin receptor 2
      gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2
      [AQP2])-provide the basis for understanding of three different hereditary forms
      of "pure" diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked
      nephrogenic diabetes insipidus (NDI), and non-X-linked NDI, respectively. It is
      clinically useful to distinguish two types of hereditary NDI: A "pure" type
      characterized by loss of water only and a complex type characterized by loss of
      water and ions. Patients who have congenital NDI and bear mutations in the AVPR2
      or AQP2 genes have a "pure" NDI phenotype with loss of water but normal
      conservation of sodium, potassium, chloride, and calcium. Patients who bear
      inactivating mutations in genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA and CLCNKB in
      combination, or BSND) that encode the membrane proteins of the thick ascending
      limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of
      water, sodium, chloride, calcium, magnesium, and potassium. These advances
      provide diagnostic and clinical tools for physicians who care for these patients.

PMID- 16093449
TI  - Bradykinin signaling counteracts cAMP-elicited aquaporin 2 translocation in renal
      cells.
AB  - Bradykinin (BK) is one of the most important peptides regulating vascular tone,
      water, and ionic balance in the body, playing a key role in controlling BP. It is
      interesting that patients with essential hypertension excrete less BK than
      normotensive individuals. For elucidating the mechanism by which BK regulates
      renal water transport that contributes to its antihypertensive effect, aquaporin
      2 (AQP2)-transfected collecting duct CD8 cells, expressing the BK type II
      receptor (BK2R), were used as an experimental model. In CD8 cells, BK
      pretreatment impaired forskolin-induced AQP2 translocation to the apical plasma
      membrane. For clarifying the signal transduction cascade associated with this
      effect, whether BK induced an increase in cytosolic calcium, via the G protein
      Gq, known to be coupled to BK2R, first was investigated. Spectrofluorometry using
      fura-2-AM revealed that 100 nM BK elicited a significant increase in Ca(i), which
      was abolished by the receptor antagonist HOE-140. BK acts through BK2R coupled to
      both Gq and Galpha13, a known upstream effector of Rho protein. In CD8 cells, BK
      causes an increase in Rho activity, likely as a result of Galpha13 activation.
      This results in stabilization of the cortical F-actin network, thus impairing
      AQP2 trafficking. These effects counteract physiologic vasopressin stimulation,
      which instead has an opposite effect on actin network organization through Rho
      inactivation.

PMID- 16093450
TI  - Protection of endothelial cells by dextran sulfate in rats with thrombotic
      microangiopathy.
AB  - The characteristic features of thrombotic microangiopathy (TMA) include
      glomerular and peritubular capillary endothelial cell injury in association with
      loss of heparan sulfate proteoglycans on the cell surface and thrombus formation,
      followed by subsequent ischemic tubulointerstitial damage. It therefore was
      hypothesized that dextran sulfate (DXS) may protect the kidney against
      endothelial damage in a model of TMA. TMA was induced in rats by renal artery
      perfusion of an antiglomerular endothelial antibody, followed by the
      administration of DXS or vehicle. Renal damage was assessed by histologic
      analysis and measurements of blood urea nitrogen and creatinine. Whereas control
      rats developed severe renal failure with extensive glomerular and tubular injury,
      administration of DXS significantly protected renal function and preserved the
      glomerular endothelium and peritubular capillaries. The beneficial effect of DXS
      could be attributed to the ability of DXS to protect endothelial cells from
      coagulation and complement activation, as demonstrated by the histologic
      analysis. In addition, binding of the administered DXS to the surface of the
      glomerular endothelium was confirmed in TMA rats, suggesting that DXS acts as a
      "repair coat" of injured glomerular endothelium. In conclusion, DXS protects the
      kidney from experimental TMA. This protection may be mediated by DXS's binding
      directly to the surface of glomerular endothelium and amelioration of
      coagulation, complement activation, and cellular matrix loss.

PMID- 16093451
TI  - Y-box protein 1 mediates PDGF-B effects in mesangioproliferative glomerular
      disease.
AB  - The pivotal role of PDGF-B for mesangioproliferative glomerular disease is well
      established. Here, Y-box protein-1 (YB-1) was identified as a downstream
      signaling target of PDGF-B. In healthy kidney cells, YB-1 was located
      predominantly within the nuclear compartment. Subsequent to PDGF-B infusion and
      in the course of anti-Thy1.1-induced mesangioproliferative glomerulonephritis,
      relocalization of YB-1 into the cytoplasm was observed. In experimental models
      that lack profound mesangial cell proliferation (e.g., Puromycin-nephrosis,
      passive Heyman nephritis, spontaneous normotensive nephrosclerosis,
      hyperlipidemic diabetic nephropathy), YB-1 remained nuclear. This translocation
      coincided with upregulation of YB-1 protein levels within the mesangial
      compartment. Increased YB-1 expression and subcellular shuttling was dependent on
      PDGF-B signaling via the mitogen-activated protein kinase pathway because these
      alterations were prevented by specific PDGF aptamers and the mitogen-activated
      protein kinase pathway inhibitor U0126. Furthermore, PDGF-B strongly induced YB-1
      expression in vitro. This induction was important because RNAi-dependent
      knockdown of YB-1 abolished the mitogenic PDGF-B effect. Taken together, YB-1
      seems to represent a specific and necessary PDGF-B target in
      mesangioproliferative glomerular disease.

PMID- 16093452
TI  - Endothelial nitric oxide synthase gene/gender interactions and the renal
      hemodynamic response to angiotensin II.
AB  - Endothelial function is dependent on the generation of nitric oxide (NO) by the
      enzyme endothelial NO synthase (eNOS). One functional coding polymorphism of the
      eNOS gene (G894-->T) is associated with reduced enzyme activity, increased
      coronary heart disease, and the development of end-stage renal failure. Because
      gender and renin-angiotensin system activation also play key roles in the
      development of renal and cardiovascular disease and because NO plays a role in
      the response to angiotensin II (AngII), it was hypothesized that the eNOS gene
      G894-->T polymorphism would be a determinant of the systemic and renal vascular
      response to AngII. Fifty young, healthy, normotensive individuals who were on a
      controlled sodium and protein diet for 1 wk underwent assessment of BP and renal
      hemodynamic function at baseline and during AngII infusion (4 ng/kg per min for
      45 min). Participants were genotyped for the eNOS gene G894-->T polymorphism and
      then segregated into groups on the basis of gender and genotype (GG versus
      GT/TT). Baseline values for renal blood flow, effective renal plasma flow, and
      GFR were lower in men with the T allele compared with men who were homozygous for
      the G allele (P = 0.03), but the polymorphism was not associated with renal
      hemodynamic function in women. The BP responses to AngII were similar in men and
      women regardless of genotype. Both multivariate linear regression and analysis of
      covariance (ANCOVA) revealed a relationship between gender and genotype. Men with
      the GT/TT genotype exhibited a significantly greater decrease in GFR (P = 0.04)
      in response to AngII than did those with the GG genotype. This association was
      not observed in women. The eNOS gene G894-->T polymorphism is a determinant of
      both baseline renal hemodynamic function and the hemodynamic response to AngII in
      men but not in women.

PMID- 16093453
TI  - Multifunctional roles for serum protein fetuin-a in inhibition of human vascular
      smooth muscle cell calcification.
AB  - Vascular calcification predicts an increased risk for cardiovascular
      events/mortality in atherosclerosis, diabetes, and ESRD. Serum concentrations of
      alpha(2)-Heremens-Schmid glycoprotein, commonly referred to as fetuin-A, are
      reduced in ESRD, a condition associated with an elevated circulating calcium x
      phosphate product. Mice that lack fetuin-A exhibit extensive soft tissue
      calcification, which is accelerated on a mineral-rich diet, suggesting that
      fetuin-A acts to inhibit calcification systemically. Western blot and
      immunohistochemistry demonstrated that serum-derived fetuin-A co-localized with
      calcified human vascular smooth muscle cells (VSMC) in vitro and in calcified
      arteries in vivo. Fetuin-A inhibited in vitro VSMC calcification, induced by
      elevated concentrations of extracellular mineral ions, in a concentration
      dependent manner. This was achieved in part through inhibition of apoptosis and
      caspase cleavage. Confocal microscopy and electron microscopy-immunogold
      demonstrated that fetuin-A was internalized by VSMC and concentrated in
      intracellular vesicles. Subsequently, fetuin-A was secreted via vesicle release
      from apoptotic and viable VSMC. Vesicles have previously been identified as the
      nidus for mineral nucleation. The presence of fetuin-A in vesicles abrogated
      their ability to nucleate basic calcium phosphate. In addition, fetuin-A enhanced
      phagocytosis of vesicles by VSMC. These observations provide evidence that the
      uptake of the serum protein fetuin-A by VSMC is a key event in the inhibition of
      vesicle-mediated VSMC calcification. Strategies aimed at maintaining normal
      circulating levels of fetuin-A may prove beneficial in patients with ESRD.

PMID- 16093454
TI  - Glomerular number and function are influenced by spontaneous and induced low
      birth weight in rats.
AB  - A link exists between low birth weight and diseases in adulthood, such as
      hypertension, cardiovascular disease, and insulin resistance. Intrauterine growth
      restriction (IUGR) has been used to explain this association and has been shown
      to lead to a nephron endowment in humans. A reduction in glomerular number has
      been described in animal models with induced low birth weight as well but not in
      animals with spontaneous low birth weight. It therefore is debatable whether the
      models are suitable. The effect on glomerular number and size was studied in rats
      with naturally occurring IUGR and experimental IUGR, induced by bilateral uterine
      artery ligation. Design-based stereologic methods were used. Urinary protein
      excretion was determined as a measure of renal damage. Results showed a decrease
      of approximately 20% in glomerular number in both groups of IUGR (control 35,400,
      naturally occurring IUGR 30,900, and experimental IUGR 28,000 glomeruli per
      kidney). Mean glomerular volume was increased in both IUGR groups, which was
      associated with an increased proteinuria. It is concluded that IUGR leads to a
      nephron endowment with a compensatory glomerular enlargement. This compensation
      is associated with more proteinuria in the long run. Uterine artery ligation in
      the pregnant rat is a suitable model to study the effects of IUGR on the kidney.

PMID- 16093455
TI  - SMN genotypes producing less SMN protein increase susceptibility to and severity
      of sporadic ALS.
AB  - BACKGROUND: ALS is believed to be multifactorial in origin with modifying genes
      affecting its clinical expression. Childhood-onset spinal muscular atrophy (SMA)
      is an autosomal recessive disorder of motor neurons, caused by mutations of the
      survival motor neuron (SMN) gene. The SMN gene exists in two highly homologous
      variants: SMN1, the causative gene responsible for the production of the majority
      of functional SMN protein, and SMN2, responsible for the production of less
      protein but sufficient for modifying the SMA phenotype. OBJECTIVE: To test
      whether SMN genotypes are associated with susceptibility to and severity of
      sporadic ALS. METHODS: We performed competitive quantitative PCR analysis for
      both SMN1 and SMN2 genes in 242 clinically well-defined ALS patients and 175
      controls. The combined determination of SMN1 and SMN2 copies also allowed for an
      estimation of the level of SMN for each patient (estimated SMN protein level =
      SMN1 copy number + 0.20 x SMN2 copy number). RESULTS: One copy of SMN1 was
      associated with an increased risk of developing ALS (odds ratio = 4.1, 95% CI =
      1.2 to 14.2, p = 0.02) and ALS patients carried fewer SMN2 copy numbers (p <
      0.001). Sixty-one percent of patients had an estimated protein SMN level < or =
      2.2 vs only 36% of controls (p = 0.0000004). Multivariate Cox regression analyses
      showed that lower SMN2 copy numbers and lower levels of estimated SMN protein
      (hazard ratio = 1.3, 95% CI = 1.1 to 1.6, p = 0.03) were associated with an
      increased mortality rate. CONCLUSIONS: SMN genotypes producing less SMN protein
      increase susceptibility to and severity of ALS.

PMID- 16093456
TI  - Early onset of inflammation and later involvement of TGFbeta in Duchenne muscular
      dystrophy.
AB  - OBJECTIVE: To identify stage-specific induction of molecular pathology pathways
      in Duchenne muscular dystrophy (DMD). METHODS: We performed mRNA profiling using
      muscles from fetopsies, infants (aged 8 to 10 months), and symptomatic patients
      (aged 5 to 12 years) with DMD, and age- and sex-matched controls. We performed
      immunohistochemistry to determine changes at the protein level and protein
      localization. RESULTS: Activated tissue dendritic cells, expression of toll-like
      receptor 7, and strong induction of nuclear factor-kappaB pathways occurred soon
      after birth in DMD muscle. Two muscle wasting pathways, atrogin-1 and myostatin,
      were not induced at any stage of the disease. Normal muscle showed accumulation
      of glycolytic and oxidative metabolism capacity with increased age, but this
      accumulation failed in DMD. The transforming growth factor (TGF)-beta pathway was
      strongly induced in symptomatic patients, with expression of TGFbeta type II
      receptor and apoptosis signal-regulating kinase 1 proteins on subsets of mature
      DMD myofibers. CONCLUSIONS: Our data show stage-specific remodeling of human
      dystrophin-deficient muscle, with inflammatory pathways predominating in the
      presymptomatic stages and acute activation of TGFbeta and failure of metabolic
      pathways later in the disease.

PMID- 16093457
TI  - Pregnancy outcomes during treatment with interferon beta-1a in patients with
      multiple sclerosis.
AB  - BACKGROUND: Although patients with multiple sclerosis (MS) are advised to stop
      interferon (IFN) beta-1a therapy before becoming pregnant, some patients become
      pregnant while on treatment. METHODS: We examined individual patient data from
      eight clinical trials with IFNbeta-1a. RESULTS: Of 3,361 women in the studies, 69
      pregnancies were reported, of which 41 were patients receiving (or who had
      stopped receiving within 2 weeks prior to conception) IFNbeta-1a (in utero
      exposure group), 22 were patients who discontinued IFNbeta-1a treatment more than
      2 weeks before conception (previous exposure group), and six were patients
      receiving placebo. The 41 in utero exposure pregnancies resulted in 20 healthy
      full-term infants, one healthy premature infant, nine induced abortions, eight
      spontaneous abortions, one fetal death, and one congenital anomaly
      (hydrocephalus). One patient was lost to follow-up. The 22 previous exposure
      pregnancies resulted in 20 full-term healthy infants, one healthy premature
      infant, and one birth-related congenital anomaly (Erb palsy). CONCLUSIONS: The
      majority (21/31) of pregnancies that had the potential to go to full term
      produced healthy infants. The rate of spontaneous abortion was higher, but not
      significantly so, in the in utero exposure group compared to general population
      estimates. Until more exposure data become available, patients remain advised to
      stop IFNbeta therapy before becoming pregnant.

PMID- 16093458
TI  - Images in clinical medicine. Patulous eustachian tube.

PMID- 16093459
TI  - The London attacks--a chronicle: Improvising in an emergency.

PMID- 16093460
TI  - The London attacks--preparedness: Terrorism and the medical response.

PMID- 16093461
TI  - The London attacks--response: Prehospital and hospital care.

PMID- 16093462
TI  - The London attacks--aftermath: Victimhood and resilience.

PMID- 16093463
TI  - Rocky Mountain spotted fever--changing ecology and persisting virulence.

PMID- 16093464
TI  - One year of alendronate after one year of parathyroid hormone (1-84) for
      osteoporosis.
AB  - BACKGROUND: Since the use of parathyroid hormone as a treatment for osteoporosis
      is limited to two years or less, the question of whether antiresorptive therapy
      should follow parathyroid hormone therapy is important. We previously reported
      results after the first year of this randomized trial comparing the use of full
      length parathyroid hormone (1-84) alone, alendronate alone, or both combined. In
      the continuation of this trial, we asked whether antiresorptive therapy is
      required to maintain gains in bone mineral density after one year of therapy with
      parathyroid hormone (1-84). METHODS: In the data reported here, women who had
      received parathyroid hormone (1-84) monotherapy (100 microg daily) in year 1 were
      randomly reassigned to one additional year with either placebo (60 subjects) or
      alendronate (59 subjects). Subjects who had received combination therapy in year
      1 received alendronate in year 2; those who had received alendronate monotherapy
      in year 1 continued with alendronate in year 2. Bone mineral density at the spine
      and hip was assessed with the use of dual-energy x-ray absorptiometry and
      quantitative computed tomography (CT). RESULTS: Over two years, alendronate
      therapy after parathyroid hormone therapy led to significant increases in bone
      mineral density in comparison with the results for placebo after parathyroid
      hormone therapy, a difference particularly evident for bone mineral density in
      trabecular bone at the spine on quantitative CT (an increase of 31 percent in the
      parathyroid hormone-alendronate group as compared with 14 percent in the
      parathyroid hormone-placebo group). During year 2, subjects receiving placebo
      lost substantial bone mineral density. CONCLUSIONS: After one year of parathyroid
      hormone (1-84), densitometric gains appear to be maintained or increased with
      alendronate but lost if parathyroid hormone is not followed by an antiresorptive
      agent. These results have clinical implications for therapeutic choices after the
      discontinuation of parathyroid hormone.

PMID- 16093465
TI  - Daily and cyclic parathyroid hormone in women receiving alendronate.
AB  - BACKGROUND: We evaluated whether patients with osteoporosis treated with long
      term alendronate have a response to parathyroid hormone treatment and whether
      short, three-month cycles of parathyroid hormone therapy could be as effective as
      daily administration. METHODS: We randomly assigned 126 women with osteoporosis
      who had been taking alendronate for at least 1 year to continued alendronate plus
      parathyroid hormone (1-34) subcutaneously daily, continued alendronate plus
      parathyroid hormone (1-34) subcutaneously daily for three 3-month cycles
      alternating with 3-month periods without parathyroid hormone, or alendronate
      alone for 15 months. RESULTS: In both parathyroid hormone groups, bone formation
      indexes rose swiftly. Among the women who were receiving cyclic parathyroid
      hormone, bone formation declined during cycles without parathyroid hormone and
      increased again during cycles with parathyroid hormone. Bone resorption increased
      in both parathyroid hormone groups but increased progressively more in the daily
      treatment group than in the cyclic-therapy group. Spinal bone mineral density
      rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic
      therapy group (P<0.001 for each parathyroid hormone group as compared with the
      alendronate group and no significant difference between parathyroid hormone
      groups). One woman in the daily-treatment group, two in the cyclic-therapy group,
      and four in the alendronate group had new or worsening vertebral deformities.
      CONCLUSIONS: This study suggests that a regimen of three-month cycles of
      parathyroid hormone alternating with three-month cycles without parathyroid
      hormone causes the early phase of action of parathyroid hormone (characterized by
      pure stimulation of bone formation) to be dissociated from the later phase
      (activation of bone remodeling). The early phase may be more important to the
      increase in spinal bone mineral density. In patients with persistent osteoporosis
      after prior alendronate treatment, both daily treatment and cyclic treatment with
      parathyroid hormone increase spinal bone mineral density.

PMID- 16093466
TI  - Developmental outcomes after early or delayed insertion of tympanostomy tubes.
AB  - BACKGROUND: To prevent later developmental impairments, myringotomy with the
      insertion of tympanostomy tubes has often been undertaken in young children who
      have persistent otitis media with effusion. We previously reported that prompt as
      compared with delayed insertion of tympanostomy tubes in children with persistent
      effusion who were younger than three years of age did not result in improved
      developmental outcomes at three or four years of age. However, the effect on the
      outcomes of school-age children is unknown. METHODS: We enrolled 6350 healthy
      infants younger than 62 days of age and evaluated them regularly for middle-ear
      effusion. Before three years of age, 429 children with persistent middle-ear
      effusion were randomly assigned to have tympanostomy tubes inserted either
      promptly or up to nine months later if effusion persisted. We assessed
      developmental outcomes in 395 of these children at six years of age. RESULTS: At
      six years of age, 85 percent of children in the early-treatment group and 41
      percent in the delayed-treatment group had received tympanostomy tubes. There
      were no significant differences in mean (+/-SD) scores favoring early versus
      delayed treatment on any of 30 measures, including the Wechsler Full-Scale
      Intelligence Quotient (98+/-13 vs. 98+/-14); Number of Different Words test, a
      measure of word diversity (183+/-36 vs. 175+/-36); Percentage of Consonants
      Correct-Revised test, a measure of speech-sound production (96+/-2 vs. 96+/-3);
      the SCAN test, a measure of central auditory processing (95+/-15 vs. 96+/-14);
      and several measures of behavior and emotion. CONCLUSIONS: In otherwise healthy
      children younger than three years of age who have persistent middle-ear effusion
      within the duration of effusion that we studied, prompt insertion of tympanostomy
      tubes does not improve developmental outcomes at six years of age.

PMID- 16093467
TI  - Rocky Mountain spotted fever from an unexpected tick vector in Arizona.
AB  - BACKGROUND: Rocky Mountain spotted fever is a life-threatening, tick-borne
      disease caused by Rickettsia rickettsii. This disease is rarely reported in
      Arizona, and the principal vectors, Dermacentor species ticks, are uncommon in
      the state. From 2002 through 2004, a focus of Rocky Mountain spotted fever was
      investigated in rural eastern Arizona. METHODS: We obtained blood and tissue
      specimens from patients with suspected Rocky Mountain spotted fever and ticks
      from patients' homesites. Serologic, molecular, immunohistochemical, and culture
      assays were performed to identify the causative agent. On the basis of specific
      laboratory criteria, patients were classified as having confirmed or probable
      Rocky Mountain spotted fever infection. RESULTS: A total of 16 patients with
      Rocky Mountain spotted fever infection (11 with confirmed and 5 with probable
      infection) were identified. Of these patients, 13 (81 percent) were children 12
      years of age or younger, 15 (94 percent) were hospitalized, and 2 (12 percent)
      died. Dense populations of Rhipicephalus sanguineus ticks were found on dogs and
      in the yards of patients' homesites. All patients with confirmed Rocky Mountain
      spotted fever had contact with tick-infested dogs, and four had a reported
      history of tick bite preceding the illness. R. rickettsii DNA was detected in
      nonengorged R. sanguineus ticks collected at one home, and R. rickettsii isolates
      were cultured from these ticks. CONCLUSIONS: This investigation documents the
      presence of Rocky Mountain spotted fever in eastern Arizona, with common brown
      dog ticks (R. sanguineus) implicated as a vector of R. rickettsii. The broad
      distribution of this common tick raises concern about its potential to transmit
      R. rickettsii in other settings.

PMID- 16093468
TI  - Clinical practice. Postmenopausal osteoporosis.

PMID- 16093469
TI  - Retinoid x receptor heterodimers in the metabolic syndrome.

PMID- 16093470
TI  - Images in clinical medicine. Chylothorax and chyloperitoneum.

PMID- 16093471
TI  - Case records of the Massachusetts General Hospital. Case 24-2005. A 58-year-old
      woman with early-stage estrogen-receptor-positive breast cancer.

PMID- 16093472
TI  - Combination and sequential therapy for osteoporosis.

PMID- 16093473
TI  - Rickettsia parkeri infection and other spotted fevers in the United States.

PMID- 16093474
TI  - Amiodarone versus sotalol for atrial fibrillation.

PMID- 16093475
TI  - Multidetector-row computed tomography in suspected pulmonary embolism.

PMID- 16093476
TI  - Detection of acute HIV infections.

PMID- 16093477
TI  - Traumatic brain injury in the war zone.

PMID- 16093478
TI  - Teriparatide, osteoporosis, calcium, and vitamin D.

PMID- 16093479
TI  - Regulation of co-repressive activity of and HDAC recruitment to RIP140 by site
      specific phosphorylation.
AB  - Receptor interacting protein 140 (RIP140) is a versatile transcriptional co
      repressor that contains several autonomous repressive domains (RDs). The N
      terminal RD acts by recruiting histone deacetylases (HDACs). In a comprehensive
      proteomic analysis of RIP140 by MS, 11 phosphorylation sites of RIP140 are
      identified; among them five sites are located in the N-terminal RD including
      Ser104, Thr202, Thr207, Ser358, and Ser380. The role of phosphorylation of RIP140
      in regulating its biological activity and the underlying mechanism are examined
      using a site-directed mutagenesis approach. Mutations mimicking constitutive
      phosphorylation or dephosphorylation are introduced. The N-terminal RD
      phosphorylation, mediated by the mitogen-activated protein kinase (MAPK),
      enhances its repressive activity through increased recruitment of HDAC. Mutations
      mimicking constitutive dephosphorylation at Thr202 or Thr207 significantly impair
      its repressive activity and HDAC recruitment, whereas mutation at Ser358 only
      slightly affects its HDAC recruitment and the repressive activity. Consistently,
      mutations mimicking constitutive phosphorylation at either Thr202 or Thr207
      convert RIP140 into a more potent repressor, which is less responsive to a
      disturbance in the MAPK system. Furthermore, constitutive phosphorylation at both
      Thr202 and Thr207 residues renders RIP140 fully repressive and strongly
      interacting with HDAC. The activity of this mutant is resistant to the MAPK
      inhibitor, indicating an essential role for Thr202 and Thr207 in MAPK-mediated
      modulation of RIP140 function. The study provides insights into the modulation of
      RIP140 biological activity through a specific cellular signaling pathway that
      augments phosphorylation at specific residues of RIP140 molecule and alters its
      cofactor recruitment.

PMID- 16093480
TI  - From organ to molecules: steps and consequences.
AB  - The classic cardiac research programs revolved around measurable properties such
      as pressures, work done, vascular blood flow, electrical propagation, and other
      such parameters that defined the global heart functions in health and decease.
      Consistently, the first Henry Goldberg Workshop, held in Haifa in 1984, focused
      on the interactions between cardiac mechanics, electrical activation, perfusion,
      and metabolism of the whole heart. Questions focused on the macroscale cardiac
      function and performance. These studies involved engineering science, simulation,
      and modeling tools that were essential for the understanding of the complex
      interactions within the cardiac system. Three-dimensional imaging, ventricular
      structure, fiber mechanics, circulation and cardiovascular flow, electrical
      propagation, and blood pumping were all major foci of research at that time.
      However, it was soon obvious that in order to understand organ level
      characteristics, one must explore the complex cellular and intracellular control
      mechanisms; these became the foci of our subsequent workshops. Better
      understanding of organ level performance required integrated studies of organ and
      tissue structure and function with genetic, molecular, and cellular
      characteristics, including cellular communication and ionic and molecular
      signaling. Analysis of the cardiac system thus depends on continuous probing of
      the heart system with modern measurement techniques and on integrating data and
      acquired knowledge with analytical models, constantly evolving to match reality.

PMID- 16093481
TI  - Evolution of the heart from bacteria to man.
AB  - This review provides an overview of the evolutionary path to the mammalian heart
      from the beginnings of life (about four billion years ago ) to the present.
      Essential tools for cellular homeostasis and for extracting and burning energy
      are still in use and essentially unchanged since the appearance of the
      eukaryotes. The primitive coelom, characteristic of early multicellular organisms
      ( approximately 800 million years ago), is lined by endoderm and is a passive
      receptacle for gas exchange, feeding, and sexual reproduction. The cells around
      this structure express genes homologous to NKX2.5/tinman, and gradual
      specialization of this "gastroderm" results in the appearance of mesoderm in the
      phylum Bilateria, which will produce the first primitive cardiac myocytes.
      Investment of the coelom by these mesodermal cells forms a "gastrovascular"
      structure. Further evolution of this structure in the bilaterian branches Ecdysoa
      (Drosophila) and Deuterostoma (amphioxus) culminate in a peristaltic tubular
      heart, without valves, without blood vessels or blood, but featuring a single
      layer of contracting mesoderm. The appearance of Chordata and subsequently the
      vertebrates is accompanied by a rapid structural diversification of this
      primitive linear heart: looping, unidirectional circulation, an enclosed
      vasculature, and the conduction system. A later innovation is the parallel
      circulation to the lungs, followed by the appearance of septa and the four
      chambered heart in reptiles, birds, and mammals. With differentiation of the
      cardiac chambers, regional specialization of the proteins in the cardiac myocyte
      can be detected in the teleost fish and amphibians. In mammals, growth
      constraints are placed on the heart, presumably to accommodate the constraints of
      the body plan and the thoracic cavity, and adult cardiac myocytes lose the
      ability to re-enter the cell cycle on demand. Mammalian cardiac myocyte
      innervation betrays the ancient link between the heart, the gut, and
      reproduction: the vagus nerve controlling heart rate emanates from centers in the
      central nervous system regulating feeding and affective behavior.

PMID- 16093482
TI  - The miscommunicative cardiac cell: when good proteins go bad.
AB  - Troponin (Tn) is made up of three subunits, troponin T (TnT), troponin I (TnI),
      and troponin C (TnC). In cardiac muscle, TnI can exist as two isoforms, slow
      skeletal TnI (ssTnI) or cardiac TnI (cTnI), whereas TnT occurs as multiple
      isoforms. The predominant form of TnI in fetal cardiac muscle is ssTnI, which is
      derived from a different gene than cTnI. However, the predominant form of cardiac
      TnT (cTnT) in fetal muscle is cTnT1, which is derived from the same gene that
      produces the adult cTnT isoform (cTnT3). Fetal cardiac muscle is more sensitive
      to Ca(2+) than adult muscle and this may be due in part to the fetal cTnT1 and
      ssTnI isoforms. cTnT1 and/or ssTnI by themselves cause a significant increase in
      Ca(2+) sensitivity when compared to cTnT3 and/or cTnI. Mutations in the gene for
      cTnT can cause hypertrophic cardiomyopathy or dilated cardiomyopathy (DCM).
      Investigation of DCM mutations in the fetal cTnT1 isoform showed that the cTnT
      isoform is an important determinant of the effect of the mutation. The TnI
      isoform also affects the physiological function of the cardiac muscle. The
      presence of both the fetal TnT isoform, containing a DCM mutation, and ssTnI
      results in larger changes in Ca(2+) sensitivity than the same DCM mutant in the
      adult TnT isoform and in the presence of cTnI (when compared to their respective
      wild-type TnT controls). These recent results suggest that some mutations may
      have different severities in fetal and adult hearts.

PMID- 16093483
TI  - Multiple stem cell populations contribute to the formation of the myocardium.
AB  - Owing to the very rapid growth of the vertebrate embryo following fertilization,
      an efficient circulatory system needs to be established during the initial stages
      of development. For that reason, the first functional organ that develops in both
      the bird and mammalian embryo is the heart. Until recently, the narrative of
      cardiac development was portrayed in a straightforward manner, with all the
      myocardium in the mature heart being generated from the expansion of an original
      pool of myocardial cells present in the early gastrula. It is now known that the
      story of the developing myocardium is more dynamic, as it is comprises cellular
      components of multiple ancestries. The de novo addition of myocytes to the
      developing heart occurs at various points during embryogenesis, as cardiac muscle
      takes on new members by the absorption of cells that either reside in neighboring
      nonmuscle tissue or come into contact with the myocardium by entering the heart
      upon migration or via the circulation. This article reviews what is presently
      known about cellular populations that contribute to the myocardium and examine
      reasons why the embryo utilizes multiple cellular sources for forming the cardiac
      muscle.

PMID- 16093484
TI  - Differentiation pathways in human embryonic stem cell-derived cardiomyocytes.
AB  - Human embryonic stem (hES) cells are pluripotent cell lines derived from the
      inner cell mass of the blastocyst-stage embryo. These unique cell lines can be
      propagated in the undifferentiated state in culture, while retaining the capacity
      to differentiate into derivatives of all three germ layers, including
      cardiomyocytes. The derivation of the hES cell lines presents a powerful tool to
      explore the early events of cardiac progenitor cell specification and
      differentiation, and it also provides a novel cell source for the emerging field
      of cardiovascular regenerative medicine. A spontaneous differentiation system of
      these stem cells to cardiomyocytes was established and the generated myocytes
      displayed molecular, structural, and functional properties of early-stage heart
      cells. In order to follow the in vitro differentiation process, the temporal
      expression of signaling molecules and transcription factors governing early
      cardiac differentiation was examined throughout the process. A characteristic
      pattern was noted recapitulating the normal in vivo cardiac differentiation
      scheme observed in other model systems. This review discusses the known pathways
      involved in cardiac specification and the possible factors that may be used to
      enhance cardiac differentiation of hES cells, as well as the steps required to
      fully harness the enormous potential of these unique cells.

PMID- 16093485
TI  - Functional properties of human embryonic stem cell-derived cardiomyocytes.
AB  - Regeneration of the diseased myocardium by cardiac cell transplantation is an
      attractive therapeutic modality. Yet, because the transplanted cardiomyocytes
      should functionally integrate within the diseased myocardium, it is preferable
      that their properties resemble those of the host. To determine the functional
      adaptability of human embryonic stem cell-derived cardiomyocytes (hESC-CM) to the
      host myocardium, the authors investigated the excitation-contraction (E-C)
      coupling and the responsiveness to common physiological stimuli. The main
      findings are: (1) hESC-CM readily respond to electrical pacing and generate
      corresponding [Ca(2+)](i) transients (measured by fura-2 fluorescence) and
      contractions (measured by video edge detector). (2) In contrast to the mature
      myocardium, hESC-CM display negative force-frequency relations. (3) The hESC-CM
      contraction is dependent on [Ca(2+)](o) and blocked by verapamil. (4)
      Surprisingly, ryanodine, the sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase
      inhibitor thapsigargin, and caffeine do not affect the [Ca(2+)](i) transient or
      contraction. Collectively, these results indicate that at the developmental stage
      of 45 to 60 days, the contraction is largely dependent on [Ca(2+)](o) rather than
      on sarcoplasmic reticulum (SR) Ca(2+) stores. The results show for the first time
      that the E-C coupling properties of hESC-CM differ from the adult myocardium,
      probably due to immature SR function. Based on these findings, genetic
      manipulation of hESC-CM toward the adult myocardium should be considered.

PMID- 16093486
TI  - The assembly of calcium release units in cardiac muscle.
AB  - Calcium release units (CRUs) are constituted of specialized junctional domains of
      the sarcoplasmic reticulum (jSR) that bear calcium release channels, also called
      ryanodine receptors (RyRs). In cardiac muscle, CRUs come in three subtypes that
      differ in geometry, but have common molecular components. Peripheral couplings
      are formed by a junction of the jSR with the plasmalemma; dyads occur where the
      jSR is associated with transverse (T)-tubules; corbular SR is a jSR domain that
      is located within the cells and bears RyRs but does not associate with either
      plasmalemma or T-tubules. Using transmission electron microscopy, this study
      followed the formation of CRUs and their accrual of four components: the L-type
      channel dihydropyridine receptors (DHPRs) of plasmalemma/T-tubules; the RyRs of
      jSR; triadin (Tr) and junctin (JnC), two homologous components of the jSR
      membrane; and calsequestrin (CSQ), the internal calcium binding proteins. During
      differentiation, peripheral couplings are formed first and the others follow.
      RyRs and DHPRs are targeted to subdomains of the CRUs that face each other and
      are acquired in a concerted manner. Overexpressions of either junction (JnC or
      Tr) and of CSQ, singly or in conjunction, shed light on the specific role of JnC
      in the structural development, organization, and maintenance of jSR cisternae and
      on the independent synthetic pathways and targeting of JnC and CSQ. In addition,
      the structural cues provided by the overexpression models allow us to define
      sequential steps in the synthetic pathway for JnC and CSQ and their targeting to
      the CRUs of differentiating myocardium.

PMID- 16093487
TI  - Calcium signaling in cardiac ventricular myocytes.
AB  - Calcium (Ca) is a multifunctional regulator of diverse cellular functions. In
      cardiac muscle Ca is a direct central mediator of electrical activation, ion
      channel gating, and excitation-contraction (E-C) coupling that all occur on the
      millisecond time scale. The key amplification step in E-C coupling is under tight
      control of very local [Ca]. Ca also directly activates signaling via kinases and
      phosphatases (e.g., Ca-calmodulin-dependent protein kinase [CaMKII] and
      calcineurin) that occur over a longer time scale (seconds to minutes), and the co
      localization of these Ca-dependent modulators to their targets and to Ca is also
      critical in distinct signaling pathways. Finally, Ca-dependent signaling is also
      involved in long-term (minutes to hours/days) alterations in gene expression (or
      excitation-transcription coupling). These pathways are involved in hypertrophy
      and heart failure, and they can alter the expression of some of the key Ca
      regulatory proteins involved in E-C coupling and their regulation by kinases and
      phosphatases. There may again be physical microenvironments involved in this
      nuclear transcription, such that they sense a discrete Ca signal that is distinct
      from that involved in E-C coupling. In this way cells can use Ca signaling in
      multiple ways that function in spatially and temporally distinct manners.

PMID- 16093488
TI  - Calcium biology of the transverse tubules in heart.
AB  - Ca(2+) sparks in heart muscle are activated on depolarization by the influx of
      Ca(2+) through dihydropyridine receptors in the sarcolemmal (SL) and transverse
      tubule (TT) membranes. The cardiac action potential is thus able to synchronize
      the [Ca(2+)](i) transient as Ca(2+) release is activated throughout the cell.
      Increases in the amount of Ca(2+) within the sarcoplasmic reticulum (SR) underlie
      augmented Ca(2+) release globally and an increase in the sensitivity of the
      ryanodine receptors (RyRs) to be triggered by the local [Ca(2+)](i). In a similar
      manner, phosphorylation of the RyRs by protein kinase A (PKA) increases the
      sensitivity of the RyRs to be activated by local [Ca(2+)](i). Heart failure and
      other cardiac diseases are associated with changes in SR Ca(2+) content,
      phosphorylation state of the RyRs, [Ca(2+)](i) signaling defects and arrhythmias.
      Additional changes in transverse tubules and nearby junctional SR may contribute
      to alterations in local Ca(2+) signaling. Here we briefly discuss how TT
      organization can influence Ca(2+) signaling and how changes in SR Ca(2+) release
      triggering can influence excitation-contraction (EC) coupling. High speed imaging
      methods are used in combination with single cell patch clamp experiments to
      investigate how abnormal Ca(2+) signaling may be regulated in health and disease.
      Three issues are examined in this presentation: (1) normal Ca(2+)-induced Ca(2+)
      release and Ca(2+) sparks, (2) abnormal SR Ca(2+) release in disease, and (3) the
      triggering and propagation of waves of elevated [Ca(2+)](i).

PMID- 16093489
TI  - Multimodality of Ca2+ signaling in rat atrial myocytes.
AB  - It has been suggested that the multiplicity of Ca(2+) signaling pathways in
      atrial myocytes may contribute to the variability of its function. This article
      reports on a novel Ca(2+) signaling cascade initiated by mechanical forces
      induced by "puffing" of solution onto the myocytes. Ca(i) transients were
      measured in fura-2 acetoxymethyl (AM) loaded cells using alternating 340- and 410
      nm excitation waves at 1.2 kHz. Pressurized puffs of bathing solutions, applied
      by an electronically controlled micro-barrel system, activated slowly
      (approximately 300 ms) developing Ca(i) transients that lasted 1,693 +/- 68 ms at
      room temperature. Subsequent second and third puffs, applied at approximately 20
      s intervals activated significantly smaller or no Ca(i) transients. Puff
      triggered Ca(i) transients could be reactivated once again following caffeine (10
      mM)-induced release of Ca(2+) from sarcoplasmic reticulum (SR). Puff-triggered
      Ca(i) transients were independent of [Ca(2+)](o), and activation of voltage-gated
      Ca(2+) or cationic stretch channels or influx of Ca(2+) on Na(+)/Ca(2+)exchanger,
      because puffing solution containing no Ca(2+), 10 microM diltiazem, 1 mM Cd(2+),
      5 mM Ni(2+), or 100 microM Gd(3+) failed to suppress them. Puff-triggered Ca(i)
      transients were enhanced in paced compared to quiescent myocytes. Electrically
      activated Ca(i) transients triggered during the time course of puff-induced
      transients were unaltered, suggesting functionally separate Ca(2+) pools.
      Contribution of inositol 1,4,5-triphosphate (IP(3))-gated or mitochondrial Ca(2+)
      pools or modulation of SR stores by nitric oxide/nitric oxide synthase (NO/NOS)
      signaling were evaluated using 0.5 to 500 microM 2-aminoethoxydiphenyl borate (2
      APB) and 0.1 to 1 microM carbonylcyanide-p-trifluoromethoxyphenylhydrazone
      (FCCP), and 1 mM Nomega-Nitro-L-arginine methyl ester (L-NAME) and 7
      nitroindizole, respectively. Only FCCP appeared to significantly suppress the
      puff-triggered Ca(i) transients. It was concluded that neither Ca(2+) influx nor
      depolarization was required for activation of this signaling pathway. These
      studies suggest that pressurized puffs of solutions activate a mechanically
      sensitive receptor, which signals in turn the release of Ca(2+) from a limited
      Ca(2+) store of mitochondria. How mechanical forces are sensed and transmitted to
      mitochondria to induce Ca(2+) release and what role such a Ca(2+) signaling
      pathway plays in the physiology or pathophysiology of the heart remain to be
      worked out.

PMID- 16093490
TI  - Effects of Na+-Ca2+ exchange expression on excitation-contraction coupling in
      genetically modified mice.
AB  - We have created genetically altered mice to investigate how expression of the
      Na(+)-Ca(2+) exchange protein alters excitation-contraction (E-C) coupling.
      Whereas low levels of exchanger overexpression have minimal effects on E-C
      coupling properties, high levels of overexpression in homozygous animals results
      in susceptibility to hypertrophy and heart failure, along with a significant
      reduction in E-C coupling gain. While global knockout of the exchanger in mice is
      embryonic-lethal, conditional knockout mice live to adulthood. Cardiac function
      is surprisingly normal in seven-week-old mice, but E-C coupling gain is
      apparently increased. Thus, genetic modification of exchanger expression has a
      major influence on E-C coupling.

PMID- 16093491
TI  - Mitochondrial calcium signaling and energy metabolism.
AB  - A computational model of energy metabolism in the mammalian ventricular myocyte
      is developed to study the effect of cytosolic calcium (Ca(2+)) transients on
      adenosine triphosphate (ATP) production. The model couples the Jafri-Dudycha
      model for tricarboxylic acid cycle regulation to a modified version of the Magnus
      Keizer model for the mitochondria. The fluxes associated with Ca(2+) uptake and
      efflux (i.e., the Ca(2+) uniporter and Na(+)-Ca(2+) exchanger) and the F(1)F(0)
      ATPase were modified to better model heart mitochondria. Simulations were
      performed at steady state and with Ca(2+) transients at various pacing
      frequencies generated by the Rice-Jafri-Winslow model for the guinea pig
      ventricular myocyte. The effects of the Ca(2+) transients for mitochondria both
      adjacent to the dyadic space and in the bulk myoplasm were studied. The model
      shows that Ca(2+) activation of both the tricarboxylic acid cycle and the
      F(1)F(0)-ATPase are necessary to produce increases in ATP production. The model
      also shows that in mitochondria located near the subspace, the large Ca(2+)
      transients can depolarize the mitochondrial membrane potential sufficiently to
      cause a transient decline in ATP production. However, this transient is of short
      duration, minimizing its impact on overall ATP production.

PMID- 16093492
TI  - Rhythmic Ca2+ oscillations drive sinoatrial nodal cell pacemaker function to make
      the heart tick.
AB  - Excitation-induced Ca(2+) cycling into and out of the cytosol via the
      sarcoplasmic reticulum (SR) Ca(2+) pump, ryanodine receptor (RyR) and Na(+)
      Ca(2+) exchanger (NCX) proteins, and modulation of this Ca(2+)cycling by beta
      adrenergic receptor (beta-AR) stimulation, governs the strength of ventricular
      myocyte contraction and the cardiac contractile reserve. Recent evidence
      indicates that heart rate modulation and chronotropic reserve via beta-ARs also
      involve intracellular Ca(2+) cycling by these very same molecules. Specifically,
      sinoatrial nodal pacemaker cells (SANC), even in the absence of surface membrane
      depolarization, generate localized rhythmic, submembrane Ca(2+) oscillations via
      SR Ca(2+) pumping-RyR Ca(2+) release. During spontaneous SANC beating, these
      rhythmic, spontaneous Ca(2+) oscillations are interrupted by the occurrence of an
      action potential (AP), which activates L-type Ca(2+) channels to trigger SR
      Ca(2+) release, unloading the SR Ca(2+) content and inactivating RyRs. During the
      later part of the subsequent diastolic depolarization (DD), when Ca(2+) pumped
      back into the SR sufficiently replenishes the SR Ca(2+) content, and Ca(2+)
      dependent RyR inactivation wanes, the spontaneous release of Ca(2+) via RyRs
      again begins to occur. The local increase in submembrane [Ca(2+)] generates an
      inward current via NCX, enhancing the DD slope, modulating the occurrence of the
      next AP, and thus the beating rate. Beta-AR stimulation increases the submembrane
      Ca(2+) oscillation amplitude and reduces the period (the time from the prior AP
      triggered SR Ca(2+) release to the onset of the local Ca(2+) release during the
      subsequent DD). This increased amplitude and phase shift causes the NCX current
      to occur at earlier times following a prior beat, promoting the earlier arrival
      of the next beat and thus an increase in the spontaneous firing rate. Ca(2+)
      cycling via the SR Ca(2+) pump, RyR and NCX, and its modulation by beta-AR
      stimulation is, therefore, a general mechanism of cardiac chronotropy and
      inotropy.

PMID- 16093493
TI  - Modification of cellular communication by gene transfer.
AB  - Hope has been expressed that gene and cell therapies will one day reduce the
      morbidity and mortality associated with cardiovascular diseases. Work in these
      fields has shown that the road from bench to bedside is filled with obstacles.
      Still, the possibility for treatment or even cure of cardiac disease is real.
      Continuing work will improve understanding of the underlying physiology and
      vector biology. The current review focuses on the potential use of gene therapy
      to affect cellular communication. Included is a review of communication effects
      on a transcellular level with angiogenesis, AV nodal conduction and sinus nodal
      automaticity, and effects on an intracellular level with cardiac myocyte
      repolarization. Challenges facing the field of gene therapy are also reviewed. If
      these problems can be solved, gene therapy will become a viable alternative for
      clinical use.

PMID- 16093494
TI  - Caveolae and lipid rafts: G protein-coupled receptor signaling microdomains in
      cardiac myocytes.
AB  - A growing body of data indicates that multiple signal transduction events in the
      heart occur via plasma membrane receptors located in signaling microdomains.
      Lipid rafts, enriched in cholesterol and sphingolipids, form one such microdomain
      along with a subset of lipid rafts, caveolae, enriched in the protein caveolin.
      In the heart, a key caveolin is caveolin-3, whose scaffolding domain is thought
      to serve as an anchor for other proteins. In spite of the original morphologic
      definition of caveolae ("little caves"), most work related to their role in
      compartmenting signal transduction molecules has involved subcellular
      fractionation or immunoprecipitation with anti-caveolin antibodies. Use of such
      approaches has documented that several G protein-coupled receptors (GPCR), and
      their cognate heterotrimeric G proteins and effectors, localize to lipid
      rafts/caveolae in neonatal cardiac myocytes. Our recent findings support the view
      that adult cardiac myocytes appear to have different patterns of localization of
      such components compared to neonatal myocytes and cardiac fibroblasts. Such
      results imply the existence of multiple subcellular microdomains for GPCR
      mediated signal transduction in cardiac myocytes, in particular adult myocytes,
      and raise a major unanswered question: what are the precise mechanism(s) that
      determine co-localization of GPCR and post-receptor components with lipid
      rafts/caveolae in cardiac myocytes and other cell types?

PMID- 16093495
TI  - Nitric oxide and the heart: update on new paradigms.
AB  - The role of nitric oxide (NO) as a regulator of cardiac contraction was suggested
      in the early nineties, but a consensual view of its main functions in cardiac
      physiology has only recently emerged with the help of experiments using genetic
      deletion or overexpression of the three nitric oxide synthase (NOS) isoforms in
      cardiomyocytes. Contrary to the effects of exogenous, pharmacologic NO donors,
      signaling by endogenous NO is restricted to intracellular effectors co-localized
      with NOS in specific subcellular compartments. This both ensures coordinate
      signaling by the three NOS isoforms on different aspects of the cardiomyocyte
      function and helps to reconcile previous apparently contradictory observations
      based on the use of non-isoform-specific NOS inhibitors. This review will
      emphasize the role of NOS on excitation-contraction coupling in the normal and
      diseased heart. Endothelial NOS and neuronal NOS contribute to maintain an
      adequate balance between adrenergic and vagal input to the myocardium and
      participate in the early and late phases of the Frank-Starling adaptation of the
      heart. At the early phases of cardiac diseases, inducible NOS reinforces these
      effects, which may become maladaptive as disease progresses.

PMID- 16093496
TI  - Cardiac neurobiology of nitric oxide synthases.
AB  - Nitric oxide (NO) is a potent modulator of cardiac and vascular regulation. Its
      role in cardiac-autonomic neural signaling has received much attention over the
      last decade because of the ability of NO to alter cardiac sympathovagal balance
      to favor more anti-arrhythmic states. Complexity and controversy have arisen,
      however, because of the numerous sources of NO in the brain, peripheral nerves,
      and cardiomyocytes, all of which are potential regulators of cardiac excitability
      and calcium signaling. This review addresses the integrative role of NO as a
      relatively ubiquitous signaling molecule with respect to cardiac neurobiology.
      The present idea, that divergent NO-signaling pathways from multiple sources
      within the heart and nervous system converge to modulate cardiac excitability and
      impact on morbidity and mortality in health and disease, is discussed.

PMID- 16093497
TI  - The murine cardiac 26S proteasome: an organelle awaiting exploration.
AB  - Multiprotein complexes have been increasingly recognized as essential functional
      units for a variety of cellular processes, including the protein degradation
      system. Selective degradation of proteins in eukaryotes is primarily conducted by
      the ubiquitin proteasome system. The current knowledge base, pertaining to the
      proteasome complexes in mammalian cells, relies largely upon information gained
      in the yeast system, where the 26S proteasome is hypothesized to contain a 20S
      multiprotein core complex and one or two 19S regulatory complexes. To date, the
      molecular structure of the proteasome system, the proteomic composition of the
      entire 26S multiprotein complexes, and the specific designated function of
      individual components within this essential protein degradation system in the
      heart remain virtually unknown. A functional proteomic approach, employing
      multidimensional chromatography purification combined with liquid chromatography
      tandem mass spectrometry and protein chemistry, was utilized to explore the
      murine cardiac 26S proteasome system. This article presents an overview on the
      subject of protein degradation in mammalian cells. In addition, this review
      shares the limited information that has been garnered thus far pertaining to the
      molecular composition, function, and regulation of this important organelle in
      the cardiac cells.

PMID- 16093498
TI  - Metabolic energetics and genetics in the heart.
AB  - From the first stages of differentiation in the embryo to the end of life, energy
      substrate metabolism and function are inextricably linked features of the heart.
      The principle of energy substrate metabolism is simple. For a given developmental
      stage and for a given environment, the heart oxidizes the most efficient fuel on
      the path to ATP. The "multitasking" of energy substrate metabolism in the heart
      entails more than the generation of reducing equivalents for oxidative
      phosphorylation of ADP in the respiratory chain. In the postnatal heart,
      substrate switching and metabolic flexibility are features of normal function. In
      the stressed heart, metabolic remodeling precedes, triggers, and sustains
      functional and structural remodeling. This manuscript reviews the pleiotropic
      actions of metabolism in energy transfer, signal transduction, cardiac growth,
      gene expression, and viability. Examples are presented to illustrate that
      metabolic signals of stressed and failing heart are the product of complex
      cellular processes. An early feature of the maladapted heart is a loss of
      metabolic flexibility. The example of lipotoxic heart failure illustrates the
      concept of sustained metabolic dysregulation as a cause of contractile
      dysfunction of the heart. Thus, a paradigm emerges in which metabolic signals not
      only regulate fluxes through enzyme catalyzed reactions in existing metabolic
      pathways, but also regulate transcriptional, translational, and post
      translational signaling in the heart. As new insights are gained into metabolic
      adaptation and maladaptation of the heart, metabolic modulation may become an
      effective strategy for the treatment of heart failure.

PMID- 16093499
TI  - The sarcomeric control of energy conversion.
AB  - The Frank-Starling Law, Fenn Effect, and Suga's suggestions of cardiac muscle
      constant contractile efficiency establish the dependence of cardiac mechanics and
      energetics on the loading conditions. Consistent with these observations, this
      review suggests that the sarcomere control of contraction consists of two
      dominant feedbacks: (1) a cooperativity mechanism (positive feedback), whereby
      the number of force-generating cross-bridges (XBs) determines the affinity of
      calcium binding to the troponin regulatory protein; and (2) a mechanical
      (negative) feedback, whereby the filament shortening velocity affects the rate of
      XB turnover from the force to the non-force generating conformation. The study
      explains the roles of these feedbacks in providing the adaptive control of energy
      consumption by the loading conditions and validates the dependence of the
      cooperativity mechanism on the number of strong XBs. The cooperativity mechanism
      regulates XB recruitment. It explains the cardiac force-length calcium
      relationship, the related Frank-Starling Law of the heart, and the adaptive
      control of new XB recruitment and the associated adenosine triphosphate (ATP)
      consumption. The mechanical feedback explains the force-velocity relationship and
      the constant and high-contractile efficiency. These mechanisms were validated by
      testing the force responses to large amplitude (100 nm/sarcomere) sarcomere
      length (SL) oscillations, in intact tetanized trabeculae (utilizing 30 microM
      cyclopiazonic). The force responses to large-length oscillations lag behind the
      imposed oscillations at low extracellular calcium concentration ([Ca(2+)](0)) and
      slow frequencies (<4 Hz, 25 degrees C), yielding counterclockwise hystereses in
      the force-length plane. The force was higher during shortening than during
      lengthening. The area within these hystereses corresponds to the external work
      generated from new XB recruitment during each oscillation, and it is determined
      by the delay in the force response. Characterization of the delayed response and
      its dependence on the SL, force, and calcium allows identification of the
      regulation of XB recruitment. The direct dependence of the phase on force
      indicates that XB recruitment is determined directly by the force (i.e., the
      number of strong XBs) and indirectly by SL or calcium. The suggested feedbacks
      determine cardiac energetics: 1) the constant and high contractile efficiency is
      an intrinsic property of the single XB, due to the mechanical feedback; and 2)
      the XBs are the myocyte sensors that modulate XB recruitment in response to
      length and load changes through the cooperativity mechanism.

PMID- 16093500
TI  - Structure-function relation of the myosin motor in striated muscle.
AB  - Force and shortening in striated muscle are driven by a structural working stroke
      in the globular portion of the myosin molecules-the myosin head-that cross-links
      the myosin-containing filaments and the actin-containing filaments. We use time
      resolved X-ray diffraction in single fibers from frog skeletal muscle to link the
      conformational changes in the myosin head determined at atomic resolution in
      crystallographic studies with the kinetic and mechanical features of the
      molecular motor in the preserved sarcomeric structure. Our approach exploits the
      improved brightness and collimation of the X-ray beams of the third generation
      synchrotrons by using X-ray interference between the two arrays of myosin heads
      in each bipolar myosin filament to measure with A sensitivity the axial motions
      of myosin heads in situ during the synchronous execution of the working stroke
      elicited by rapid decreases in length or load imposed during an active isometric
      contraction. Changes in the intensity and interference-fine structure of the
      axial X-ray reflections following the mechanical perturbation allowed to
      establish the average conformation of the myosin heads during the active
      isometric contraction and the extent of tilt during the elastic response and
      during the subsequent working stroke. The myosin working stroke is 12 nm at low
      loads, which is consistent with crystallographic studies, while it is smaller and
      slower at higher loads. The load dependence of the size and speed of the myosin
      working stroke is the molecular determinant of the macroscopic performance and
      efficiency of muscle.

PMID- 16093501
TI  - Mitochondria and ischemia/reperfusion injury.
AB  - Cardiac ischemia/reperfusion injury results in a variable mixture of apoptotic,
      necrotic, and normal tissue that depends on both the duration and severity of
      ischemia. Injury can be abrogated by activation of protective pathways via
      ischemic and pharmacologic preconditioning. Mitochondria serve as final arbiters
      of life and death of the cell as these organelles not only are required to
      generate ATP but also can trigger apoptosis or necrosis. A key mechanism of
      mitochondrial injury is by the mitochondrial permeability transition (MPT) that
      has been shown to occur at reperfusion. The article hypothesizes that
      ischemia/reperfusion promotes MPT in two phases: (1) MPT priming during ischemia
      occurs as progressive inner mitochondrial membrane leak is accompanied by
      depressed electron transport in the setting of fatty acid accumulation and loss
      of cytochrome c and antioxidants; and (2) Triggering of MPT at reperfusion is
      determined by the interplay of mitochondrial membrane potential (DeltaPsi(m))
      with mitochondrial matrix Ca, reactive oxygen species, and pH. It has been found
      that strategies that promote mitochondrial recovery such as pharmacologic
      preconditioning by diazoxide are mediated by K(+)-dependent regulation of matrix
      volume and DeltaPsi(m), resulting in improved efficiency of ATP synthesis as well
      as prevention of cytochrome c loss. If mitochondria fail to recover, then MPT and
      hypercontracture can result as DeltaPsi(m) depolarization waves regeneratively
      cross the cell (0.1 to 0.2 microm/s).

PMID- 16093502
TI  - Regulation of cardiac energetics: role of redox state and cellular
      compartmentation during ischemia.
AB  - The heart is capable of altering its metabolic rate during exercise or ischemia.
      Under most state transitions, the heart maintains the concentration of adenosine
      triphosphate (ATP) at relatively constant values, in spite of large fluctuations
      in metabolic rate or in the delivery of fuels and oxygen. However, the mechanisms
      responsible for the regulation of cardiac energetics under conditions of
      increased demand or reduced supply are still under debate. To improve
      quantitative understanding of the regulation of glycolysis and oxidative
      phosphorylation under physiological and pathological conditions, it is essential
      to assess the dynamics of cytosolic and mitochondrial nicotinamide adenine
      dinucleotide (NAD(+)) and its reduced form (NADH) during stress (e.g., ischemia,
      exercise). However, at present there are no reliable methods to measure the
      dynamics of redox state in vivo in these subcellular compartments. In the present
      study, computer simulations with a mathematical model of myocardial energy
      metabolism are used to investigate the role of cytosolic and mitochondrial redox
      states in regulating cardiac energetics during reduced myocardial blood flow.

PMID- 16093503
TI  - Spatial regulation of intracellular pH in the ventricular myocyte.
AB  - In the cardiac myocyte, an adequate intracellular proton mobility is necessary
      for coupling sarcolemmal proton transport to bulk cytoplasm during intracellular
      pH regulation. It is also important for dissipating intracellular pH
      nonuniformity in response to local acid/base disturbances. Because cardiac
      myocytes have a high buffering capacity, intracellular H(+) mobility is low.
      Spatial H(i)+ movements occur via a mobile buffer shuttle that most likely
      involves intracellular dipeptides. In the present work with isolated ventricular
      myocytes, it is demonstrated that stimulating a large acid efflux on sarcolemmal
      Na(+)-H(+) exchange, results in spatial pH(i) gradients of up to 0.1 U. These may
      have important implications for pH-sensitive processes within the cell, such as
      contraction. By using computational modeling, it is shown that the gradients can
      be attributed to the low H(i)+ mobility. Computational modeling is also used to
      assess the importance of H(i)+ mobility in mediating local recovery of pH
      following an acidosis in a small region of the cell. Results indicate that local
      mechanisms for H(i)+ movement will be important in determining the global
      regulation of intracellular pH.

PMID- 16093504
TI  - Cardiac systems biology.
AB  - As more detailed molecular information accumulates on the biology of the heart
      and other complex systems in health and disease, the need for new integrative
      analyses and tools is growing. Systems biology and bioengineering seek to use
      high-throughput technologies and integrative computational analysis to construct
      networks of the interactions between molecular components in the system, to
      develop systems models of their functionally integrated biological properties,
      and to incorporate these systems models into structurally integrated multi-scale
      models for predicting clinical phenotypes. This review gives examples of recent
      applications using these approaches to elucidate the electromechanical function
      of the heart in aging and disease.

PMID- 16093505
TI  - Measuring and mapping cardiac fiber and laminar architecture using diffusion
      tensor MR imaging.
AB  - The ventricular myocardium is known to exhibit a complex spatial organization,
      with fiber orientation varying as a function of transmural location. It is now
      well established that diffusion tensor magnetic resonance imaging (DTMRI) may be
      used to measure this fiber orientation at high spatial resolution. Cardiac fibers
      are also known to be organized in sheets with surface orientation varying
      throughout the ventricles. This article reviews results on use of DTMRI for
      measuring ventricular fiber orientation, as well as presents new results
      providing strong evidence that the tertiary eigenvector of the diffusion tensor
      is aligned locally with the cardiac sheet surface normal. Considered together,
      these data indicate that DTMRI may be used to reconstruct both ventricular fiber
      and sheet organization. This article also presents the large deformation
      diffeomorphic metric mapping (LDDMM) algorithm and shows that this algorithm may
      be used to bring ensembles of imaged and reconstructed hearts into correspondence
      (e.g., registration) so that variability of ventricular geometry, fiber, and
      sheet orientation may be quantified. Ventricular geometry and fiber structure is
      known to be remodeled in a range of disease processes; however, descriptions of
      this remodeling have remained subjective and qualitative. We anticipate that use
      of DTMRI for reconstruction of ventricular anatomy coupled with application of
      the LDDMM method for image volume registration will enable the detection and
      quantification of changes in cardiac anatomy that are characteristic of specific
      disease processes in the heart. Finally, we show that epicardial electrical
      mapping and DTMRI imaging may be performed in the same hearts. The anatomic data
      may then be used to simulate electrical conduction in a computational model of
      the very same heart that was mapped electrically. This facilitates direct
      comparison and testing of model versus experimental results and opens the door to
      quantitative measurement, modeling, and analysis of the ways in which remodeling
      of ventricular microanatomy influences electrical conduction in the heart.

PMID- 16093506
TI  - Electrotonic cell-cell interactions in cardiac tissue: effects on action
      potential propagation and repolarization.
AB  - This article characterizes through computer simulations, the role of cell-cell
      interactions and of tissue structure in determining properties of action
      potential propagation and repolarization in cardiac tissue. The results
      demonstrate strong interactions between membrane excitatory processes and
      electrical loading by the passive tissue structure. These interactions modulate
      the ionic mechanism of conduction and influence conduction velocity and
      robustness. Cell-cell interactions also have a strong effect on the dispersion of
      repolarization in cardiac tissue.

PMID- 16093508
TI  - Species- and preparation-dependence of stretch effects on sino-atrial node
      pacemaking.
AB  - Acute dilation of the right atrium (e.g., via increased venous return) raises
      spontaneous beating rate (BR) of the heart in many species. Neural mechanisms
      contribute to this behavior in vivo, but a positive chronotropic response to
      stretch can also be observed in isolated right atrial tissue preparations and
      even at the level of single sino-atrial node (SAN) cells. The underlying
      mechanism has previously been reported to be compatible with stretch-activation
      of cation nonselective ion channels (SAC). This review reports species
      peculiarities in the chronotropic response of isolated SAN tissue strips to
      stretch: in contrast to guinea pig, murine SAN preparations respond to distension
      with a reduction in spontaneous BR. This differential response need not
      necessarily involve disparate (sub-)cellular mechanisms, as SAC activation would
      occur against the background of very different SAN electrophysiology in the two
      species. On the basis of single SAN cell action potential recordings, this review
      illustrates how this may give rise to potentially opposing effects on spontaneous
      BR. Interestingly, streptomycin (a useful SAC blocker in isolated cells) has no
      effect on stretch-induced chronotropy in situ, and this is interpreted as an
      indication of protection of SAC, in native tissue, from interaction with the
      drug.

PMID- 16093507
TI  - Modulation of transmural repolarization.
AB  - Ventricular myocardium in larger mammals has been shown to be comprised of three
      distinct cell types: epicardial, M, and endocardial. Epicardial and M cell action
      potentials differ from endocardial cells with respect to the morphology of phase
      1. These cells possess a prominent I(to)-mediated notch responsible for the
      "spike and dome" morphology of the epicardial and M cell response. M cells are
      distinguished from the other cell types in that they display a smaller I(Ks), but
      a larger late I(Na) and I(Na-Ca). These ionic distinctions underlie the longer
      action potential duration (APD) and steeper APD-rate relationship of the M cell.
      Difference in the time course of repolarization of phase 1 and phase 3 are
      responsible for the inscription of the electrocardiographic J wave and T wave,
      respectively. These repolarization gradients are sensitively modulated by
      electrotonic communication among the three cells types, [K(1)](o), and the
      presence of drugs that either reduce or augment net repolarizing current. A
      reduction in net repolarizing current generally leads to a preferential
      prolongation of the M cell action potential, responsible for a prolongation of
      the QT interval and an increase in transmural dispersion of repolarization (TDR),
      which underlies the development of torsade de pointes arrhythmias. An increase in
      net repolarizing current can lead to a preferential abbreviation of the action
      potential of epicardium in the right ventricle (RV), and endocardium in the left
      ventricle (LV). These actions also lead to a TDR that manifests as the Brugada
      syndrome in RV and the short QT syndrome in LV.

PMID- 16093509
TI  - Dependence of electrical coupling on mechanical coupling in cardiac myocytes:
      insights gained from cardiomyopathies caused by defects in cell-cell connections.
AB  - Cardiac myocytes are electrically coupled by large gap junctions to ensure safe
      conduction. Membrane regions containing gap junction channels are rigid and
      susceptible to fragmentation in response to shear stress. Thus, gap junctions in
      cardiac myocytes are located in close proximity to points of cell-cell adhesion
      within the intercalated disk. These adhesion junctions mechanically stabilize the
      sarcolemmas of adjacent cells to allow formation and maintenance of large arrays
      of intercellular channels. It has been proposed that the extent to which cardiac
      myocytes are coupled mechanically at cell-cell adhesion junctions is an important
      determinant of the extent to which cells can become electrically coupled at gap
      junctions. This hypothesis has been tested by analyzing gap junctions in human
      cardiomyopathies caused by mutations in plakoglobin and desmoplakin,
      intracellular proteins that link adhesion molecules at cell-cell junctions to the
      cardiac myocyte cytoskeleton. Marked remodeling of cardiac gap junctions, despite
      the presence of normal intracellular levels of connexin43, was observed. This
      suggests that defects in cell-cell adhesion, or the presence of discontinuities
      between adhesion junctions and the cytoskeleton, destabilize gap junctions and
      diminish electrical coupling. This could contribute to the high incidence of
      ventricular arrhythmias and sudden death known to occur in these
      cardiomyopathies.

PMID- 16093510
TI  - Spatial nonuniformity of contraction causes arrhythmogenic Ca2+ waves in rat
      cardiac muscle.
AB  - Landesberg and Sideman's four state model of the cardiac cross-bridge (XB)
      hypothesizes a feedback of force development to Ca(2+) binding by troponin C
      (TnC). We have further modeled this behavior and observed that the force (F)
      Ca(2+) relationship as well as the F-sarcomere length (SL) relationship and the
      time course of F and Ca(2+) transients in cardiac muscle can be reproduced
      faithfully by a single effect of F on deformation of the TnC-Ca complex and,
      thereby, on the dissociation rate of Ca(2+). Furthermore, this feedback predicts
      that rapid decline of F in the activated sarcomere causes release of Ca(2+) from
      TnC-Ca(2+), which is sufficient to initiate arrhythmogenic Ca(2+) release from
      the sarcoplasmic reticulum (SR). This work investigated the initiation of Ca(2+)
      waves underlying triggered propagated contractions (TPCs) in rat cardiac
      trabeculae under conditions that simulate functional nonuniformity caused by
      mechanical or ischemic local damage of the myocardium. A mechanical discontinuity
      along the trabeculae was created by exposing the preparation to a small constant
      flow jet of solution that reduces excitation-contraction coupling in myocytes
      within that segment. Force was measured, and SL as well as [Ca(2+)](i) were
      measured regionally. When the jet contained caffeine, 2,3-butanedione monoxime or
      low-[Ca(2+)], muscle-twitch F decreased and the sarcomeres in the exposed segment
      were stretched by shortening the normal regions outside the jet. During
      relaxation, the sarcomeres in the exposed segment shortened rapidly. Short trains
      of stimulation at 2.5 Hz reproducibly caused Ca(2+) waves to rise from the
      borders exposed to the jet. Ca(2+) waves started during F relaxation of the last
      stimulated twitch and propagated into segments both inside and outside of the
      jet. Arrhythmias, in the form of nondriven rhythmic activity, were triggered when
      the amplitude of the Ca(2+) wave increased by raising [Ca(2+)](o). The
      arrhythmias disappeared when the muscle uniformity was restored by turning the
      jet off. These results show that nonuniform contraction can cause Ca(2+) waves
      underlying TPCs, and suggest that Ca(2+) dissociated from myofilaments plays an
      important role in the initiation of arrhythmogenic Ca(2+) waves.

PMID- 16093511
TI  - Ryanodine receptor-targeted anti-arrhythmic therapy.
AB  - Cardiac arrhythmia is an important cause of death in patients with heart failure
      (HF) and inherited arrhythmia syndromes, such as catecholaminergic polymorphic
      ventricular tachycardia (CPVT). Alterations in intracellular calcium handling
      play a prominent role in the generation of arrhythmias in the failing heart.
      Diastolic calcium leak from the sarcoplasmic reticulum (SR) via cardiac ryanodine
      receptors (RyR2) may initiate delayed afterdepolarizations and triggered activity
      leading to arrhythmias. Similarly, SR Ca(2+) leak through mutant RyR2 channels
      may cause triggered activity during exercise in patients with CPVT. Novel
      therapeutic approaches, based on recent advances in the understanding of the
      cellular mechanisms underlying arrhythmias in HF and CPVT, are currently being
      evaluated to specifically correct defective Ca(2+) release in these lethal
      syndromes.

PMID- 16093512
TI  - Stem cells for cardiomyocyte regeneration: state of the art.
AB  - A wide range of stem/progenitor cell types have been used for the regeneration of
      the infarcted heart. This review details the current status of progress
      concerning different strategies that have been used to manipulate cardiomyocyte
      cell growth in vitro, for their use in heart failure. The current status of this
      field involves different types of regenerating cells. Embryonic stem (ES) cells,
      hematopoietic stem and progenitor cells, mesenchymal stem and progenitor cells,
      and resident cardiac "stem" cells are discussed here.

PMID- 16093513
TI  - Extracellular stimulation in tissue engineering.
AB  - The field of tissue engineering has created a need for biomaterials that are
      capable of providing biofunctional and structural support for living cells
      outside of the body. Most of the commonly used biomaterials in tissue engineering
      are designed based on their physicochemical properties, thus achieving precise
      control over mechanical strength, compliance, porosity, and degradation kinetics.
      Biofunctional signals are added to the scaffold by tethering, immobilizing, or
      supplementing biofunctional macromolecules, such as growth factors, directly to
      the scaffold material. The challenge in tissue engineering remains to find the
      correct balance between the biofunctional and the physical properties of the
      scaffold material for each application. Moreover, the ability to modulate
      communication between cells and the extracellular environment using the
      engineered scaffold as the actuator can provide a significant advantage in tissue
      engineering. In this study, a unique scaffold material is presented. The material
      interchangeably combines biofunctional and structural molecules by fusing the two
      into a single backbone macromolecule. This integration provides the basis for
      practical, effective, and high-resolution control of both the biofunctional and
      the physical properties of the scaffold material. This new scaffold material has
      proven effective with smooth muscle, cardiac, cartilage, and human embryonic stem
      cell cultures. The advantages of this approach as well as the potential
      applications of this unique scaffold material are discussed.

PMID- 16093515
TI  - Catastrophic thinking about pain is independently associated with pain severity,
      disability, and somatic complaints in school children and children with chronic
      pain.
AB  - OBJECTIVE: To investigate the value of pain catastrophizing in explaining pain,
      disability, and somatic complaints, beyond negative affectivity (NA). METHOD: Two
      cross-sectional studies, one in a sample of school children (n = 193) and a
      second in a clinical sample of children with recurrent or chronic pain (n = 43),
      were conducted. In both studies, measures of pain catastrophizing and NA were
      examined for their ability to explain pain, disability, and somatic complaints.
      RESULTS: In both studies, pain catastrophizing significantly accounted for the
      variance of pain, disability, and somatic complaints, beyond the effects of age,
      sex, and NA. Furthermore, pain catastrophizing significantly mediated the
      relationship between NA and somatic complaints in both studies and between NA and
      functional disability in study 1. CONCLUSIONS: Results suggest the importance of
      assessing for pain catastrophizing in children. Pain catastrophizing is further
      discussed in terms of communicating distress to significant others.

PMID- 16093516
TI  - Online psychological treatment for pediatric recurrent pain: a randomized
      evaluation.
AB  - OBJECTIVE: To evaluate the efficacy of a distance treatment delivered through
      Internet and telephone for pediatric recurrent pain. METHODS: Forty-seven
      participants (9-16 years of age) were randomly assigned to either an Internet
      based treatment or a standard medical care waitlist. Treatment employed a Web
      based manual for children and parents with weekly therapist contact by telephone
      or e-mail. At 1- and 3-month follow-ups, participants were assessed on the
      outcome variables of pain and quality of life. A 50% reduction in diary pain
      scores was considered clinically significant. RESULTS: Significant between-group
      differences were found: 71 and 72% of the treatment group achieved clinically
      significant improvement at the 1- and 3-month follow-ups, respectively, whereas
      only 19 and 14% of the control group achieved the criterion. No significant
      differences were found on the quality of life variable. CONCLUSIONS: Distance
      methods have considerable potential for making effective treatments more
      accessible with lower associated costs.

PMID- 16093514
TI  - Multiscale modeling of cardiac cellular energetics.
AB  - Multiscale modeling is essential to integrating knowledge of human physiology
      starting from genomics, molecular biology, and the environment through the levels
      of cells, tissues, and organs all the way to integrated systems behavior. The
      lowest levels concern biophysical and biochemical events. The higher levels of
      organization in tissues, organs, and organism are complex, representing the
      dynamically varying behavior of billions of cells interacting together. Models
      integrating cellular events into tissue and organ behavior are forced to resort
      to simplifications to minimize computational complexity, thus reducing the
      model's ability to respond correctly to dynamic changes in external conditions.
      Adjustments at protein and gene regulatory levels shortchange the simplified
      higher-level representations. Our cell primitive is composed of a set of
      subcellular modules, each defining an intracellular function (action potential,
      tricarboxylic acid cycle, oxidative phosphorylation, glycolysis, calcium cycling,
      contraction, etc.), composing what we call the "eternal cell," which assumes that
      there is neither proteolysis nor protein synthesis. Within the modules are
      elements describing each particular component (i.e., enzymatic reactions of
      assorted types, transporters, ionic channels, binding sites, etc.). Cell
      subregions are stirred tanks, linked by diffusional or transporter-mediated
      exchange. The modeling uses ordinary differential equations rather than
      stochastic or partial differential equations. This basic model is regarded as a
      primitive upon which to build models encompassing gene regulation, signaling, and
      long-term adaptations in structure and function. During simulation, simpler forms
      of the model are used, when possible, to reduce computation. However, when this
      results in error, the more complex and detailed modules and elements need to be
      employed to improve model realism. The processes of error recognition and of
      mapping between different levels of model form complexity are challenging but are
      essential for successful modeling of large-scale systems in reasonable time.
      Currently there is to this end no established methodology from computational
      sciences.

PMID- 16093517
TI  - Relationships between family and parent characteristics and functional abilities
      in children with recurrent pain syndromes: an investigation of moderating effects
      on the pathway from pain to disability.
AB  - OBJECTIVE: To identify family characteristics associated with children's ability
      to function with recurrent pain. METHODS: Seventy-eight children ages 7-17 years
      with recurrent pain syndromes [migraine headache or recurrent abdominal pain
      (RAP)] were recruited from clinic settings. Children completed pain diaries and
      the Functional Disability Inventory (FDI). Mothers and fathers completed self
      report measures of psychological distress, and mothers reported on family
      environment. RESULTS: Controlling for the influence of pain intensity, family
      environment and parental distress jointly predicted children's ability to
      function with pain. Among children with migraine, family environment moderated
      the relationship between pain and functional disability; in this group, greater
      pain associated with more functional disability in children from disruptive
      family environments, but not in children from more adaptive family environments.
      CONCLUSIONS: For some pediatric recurrent pain sufferers, family characteristics
      associate with the extent of pain-related disability and may help identify
      children likely to experience more impaired functioning in response to recurrent
      pain.

PMID- 16093518
TI  - Posttraumatic growth in adolescent survivors of cancer and their mothers and
      fathers.
AB  - OBJECTIVE: To describe posttraumatic growth (PTG) following childhood cancer
      survival and its association with demographic and disease/treatment variables,
      perceived treatment severity and life threat, and posttraumatic stress symptoms
      (PTSS). METHOD: Adolescent survivors of cancer (N = 150, ages 11-19), at least 1
      year after treatment, and their mothers (N = 146) and fathers (N = 107) completed
      self-report measures of perceived treatment intensity and PTSS and a
      semistructured interview designed to identify posttraumatic responses and
      indicators of PTG including perceived positive changes for self, relationships,
      and life goals. RESULTS: A majority of adolescents and their mothers and fathers
      reported PTG. Greater perceived treatment severity and life threat, but not
      objective disease severity, was associated with PTG. PTG and PTSS were positively
      associated for the adolescent cancer survivors. Diagnosis after age 5 resulted in
      more perceived benefit and greater PTSS for adolescent survivors. CONCLUSION:
      Clarification of the concept and measurement of PTG after childhood cancer is
      warranted, as are prospective studies of the association of PTG and PTSS and the
      role of demographic variables and illness-specific appraisals.

PMID- 16093519
TI  - Concerns and coping of African-American mothers after youth assault requiring
      emergency medical treatment.
AB  - OBJECTIVE: To explore maternal experience following youth assault occurring in
      the community. METHODS: A semistructured interview was used to elicit concerns
      and coping strategies among 35 African-American mothers whose children received
      emergency department (ED) treatment for assault-related injuries. Mothers also
      completed measures of violence exposure, trauma symptoms, social support, and
      youth functioning. RESULTS: The most common concerns involved family safety,
      maternal mental health, and youth externalizing behavior. Faith and social
      support were the most common coping strategies. High levels of distress were
      found, which were directly related to maternal violence exposure, relationships
      that required mothers to nurture others, and youth functioning. Distress was
      inversely related to relationships that provided guidance from others.
      CONCLUSION: Distress is common among low-income African-American mothers of youth
      assault victims. To bolster youth recovery and to reduce the risk of future
      injury, ED staff should be knowledgeable regarding culturally sensitive resources
      to address maternal distress.

PMID- 16093520
TI  - Posttraumatic stress and depressive symptoms, alcohol use, and recurrent
      traumatic life events in a representative sample of hospitalized injured
      adolescents and their parents.
AB  - OBJECTIVE: Few investigations have comprehensively assessed the scope of
      impairment of injured adolescents presenting to acute care inpatient settings.
      METHODS: Randomly sampled injured adolescent inpatients and their parents were
      screened for posttraumatic stress (PTS) and depressive symptoms, preinjury
      alcohol use, and preinjury trauma. Linear regression was used to assess which
      clinical, demographic, and injury characteristics were independently associated
      with increased levels of adolescent PTS and depressive symptoms. RESULTS: Fifty
      seven percent [corrected] of adolescent-parent dyads endorsed high levels of PTS
      or depressive symptoms and/or high preinjury alcohol use. Adolescent female
      gender, greater levels of preinjury trauma, greater subjective distress at the
      time of the injury, and greater parental depressive symptoms were independently
      associated with increased levels of adolescent PTS and depressive symptoms.
      CONCLUSIONS: The adoption of early screening and intervention procedures that
      broadly consider the scope of impairment of injured adolescents and their family
      members could enhance the quality of acute care mental health service delivery.

PMID- 16093521
TI  - Risk of posttraumatic stress symptoms: a comparison of child survivors of
      pediatric cancer and parental bereavement.
AB  - OBJECTIVE: To compare the risk of posttraumatic stress (PTS) symptoms and the
      mediating effect of perceived future threat on the risk of PTS symptoms among
      survivors of pediatric cancer and children who had a parent die. METHODS: Seventy
      eight children (39 survivors of cancer, 39 bereaved) completed self-report
      measures of PTS symptoms, depression, anxiety, and perceived risk of future
      threat for the event they experienced. RESULTS: The children who lost a parent
      reported significantly more PTS symptoms than the survivors of cancer. The effect
      of group status (survivor of cancer vs. bereaved) on PTS symptomatology was
      partly mediated by the children's perceived risk of future threat. CONCLUSIONS:
      The rate of PTS symptoms was found to be higher among children who had lost a
      parent than among survivors of pediatric cancer. This difference may partly be
      explained by their perceived risk of a future threat. Clinical implications are
      discussed.

PMID- 16093522
TI  - An integrative model of pediatric medical traumatic stress.
AB  - OBJECTIVE: To guide assessment and intervention for patients and families, a
      model for assessing and treating pediatric medical traumatic stress (PMTS) is
      presented that integrates the literature across pediatric conditions. METHODS: A
      model with three general phases is outlined--I, peritrauma; II, early, ongoing,
      and evolving responses; and III, longer-term PMTS. Relevant literature for each
      is reviewed and discussed with respect to implications for intervention for
      patients and families. RESULTS: Commonalities across conditions, the range of
      normative responses to potentially traumatic events (PTEs), the importance of
      preexisting psychological well-being, developmental considerations, and a social
      ecological orientation are highlighted. CONCLUSIONS: Growing empirical support
      exists to guide the development of assessment and intervention related to PMTS
      for patients with pediatric illness and their parents. The need for interventions
      across the course of pediatric illness and injury that target patients, families,
      and/or healthcare teams is apparent. The model provides a basis for further
      development of evidence-based treatments.

PMID- 16093524
TI  - Nonparticulate components of diesel exhaust promote constriction in coronary
      arteries from ApoE-/- mice.
AB  - Air pollution is positively associated with increased daily incidence of
      myocardial infarction and cardiovascular mortality. We hypothesize that air
      pollutants, primarily vapor phase organic compounds, cause an enhancement of
      coronary vascular constriction. Such events may predispose susceptible
      individuals to anginal symptoms and/or exacerbation of infarction. To develop
      this hypothesis, we studied the effects of nonparticulate diesel exhaust
      constituents on (1) electrocardiographic traces from ApoE-/- mice exposed whole
      body and (2) isolated, pressurized septal coronary arteries from ApoE-/- mice.
      ApoE-/- mice were implanted with radiotelemetry devices to assess
      electrocardiogram (ECG) waveforms continuously throughout exposures (6 h/day x 3
      days) to diesel exhaust (0.5 and 3.6 mg/m3) in whole-body inhalation chambers
      with or without particulates filtered. Significant bradycardia and T-wave
      depression were observed, regardless of the presence of particulates. Pulmonary
      inflammation was present only in the whole exhaust-exposed animals at the highest
      concentration. Fresh diesel exhaust or air was bubbled through the physiologic
      saline tissue bath prior to experiments to enable the isolated tissue exposure;
      exposed saline contained elevated levels of several volatile carbonyls and
      alkanes, but low to absent levels of polycyclic aromatic hydrocarbons. Vessels
      were then assayed for constrictive and dilatory function. Diesel components
      enhanced the vasoconstrictive effects of endothelin-1 and reduced the dilatory
      response to sodium nitroprusside. These data demonstrate that nonparticulate
      compounds in whole diesel exhaust elicit ECG changes consistent with myocardial
      ischemia. Furthermore, the volatile organic compounds in the vapor phase caused
      enhanced constriction and reduced dilatation in isolated coronary arteries caused
      by nonparticulate components of diesel exhaust.

PMID- 16093525
TI  - Regulatory mechanisms modulating the expression of cytochrome P450 1A1 gene by
      heavy metals.
AB  - We recently demonstrated that heavy metals, Hg2+, Pb2+, and Cu2+ induced Cyp1a1
      gene expression, yet the mechanisms involved remain unknown. To explore the
      molecular mechanisms involved in the modulation of Cyp1a1 by heavy metals, Hepa
      1c1c7 cells were treated with the metals in the presence and absence of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), a potent Cyp1a1 inducer. Time-dependent
      effect study showed that all metals significantly induced the basal Cyp1a1 mRNA.
      This was apparent 3 h after treatment, and levels remained elevated for at least
      24 h. At the inducible level, Hg2+ and Pb2+ further increased, while Cu2+
      decreased, the TCDD-mediated induction of Cyp1a1 mRNA. The RNA synthesis
      inhibitor, actinomycin D, completely blocked the Cyp1a1 induction by heavy
      metals. The protein synthesis inhibitor, cycloheximide, and 26S proteasome
      inhibitor, carbobenzoxy-L-leucyl-L-leucyl-leucinal (MG-132), super-induced the
      metal-mediated induction of Cyp1a1 mRNA. In addition, all three metals induced
      aryl hydrocarbon receptor/xenobiotic-responsive element (AhR/XRE) binding,
      suggesting an AhR-dependent mechanism. Cyp1a1 mRNA and protein decay experiments
      showed that the three metals did not significantly affect the half-life of mRNA;
      however, they significantly decreased the degradation rate of its protein,
      implying a posttranslational regulation of the Cyp1a1 by the heavy metals. A
      significant decrease in TCDD-mediated induction of Cyp1a1 activity associated
      with an increase in HO-1 mRNA and a decrease in cellular heme content was
      observed after all metals treatment. This suggests that heme degradation plays a
      role in reducing Cyp1a1 activity. This is the first demonstration that heavy
      metals can directly induce Cyp1a1 gene expression in an AhR-dependent manner
      through transcriptional and posttranslational mechanisms.

PMID- 16093526
TI  - Uptake and disposition of inhaled methanol vapor in humans.
AB  - Methanol is a widely used solvent and a potential fuel for motor vehicles. Human
      kinetic data of methanol are sparse. As a basis for biological exposure
      monitoring and risk assessment, we studied the inhalation toxicokinetics of
      methanol vapor in four female and four male human volunteers during light
      physical exercise (50 W) in an exposure chamber. The relative uptake of methanol
      was about 50% (range 47-53%). Methanol in blood increased from a background level
      of about 20 to 116 and 244 microM after 2 h exposure at 0, 100 ppm (131 mg/m3)
      and 200 ppm (262 mg/m3), respectively. Saliva showed substantially higher levels
      than blood immediately after exposure. This difference disappeared in a few
      minutes; thereafter the concentrations and time courses in blood, urine, and
      saliva were similar, with half times of 1.4, 1.7, and 1.3 h, respectively. The
      postexposure decrease of methanol in exhaled air was faster, with a half time of
      0.8 h. The methanol concentrations were approximately twice as high in all four
      types of biological samples at 200 compared to 100 ppm. No increase in urinary
      formic acid was seen in exposed subjects. Our study indicates non-saturated, dose
      proportional kinetics of methanol up to 200 ppm for 2 h. No gender differences
      were detected. Similar, parallel patterns were seen with regard to the methanol
      time courses in blood, urine, and saliva, whereas the concentration in exhaled
      air decreased markedly faster. Thus, apart from blood and urine, saliva also
      seems suitable for biomonitoring of methanol exposure.

PMID- 16093527
TI  - Induction of reactive oxygen species by bisphenol A and abrogation of bisphenol A
      induced cell injury by DJ-1.
AB  - DJ-1 was first identified as an activated ras-dependent oncogene. DJ-1 is related
      to male fertility, and its expression in sperm decreases in response to exposure
      to a number of reproductive toxicants. DJ-1 has been associated with the onset of
      familial Parkinson's disease (PD) in humans, and has been found to have activity
      against oxidative damage by eliminating reactive oxygen species (ROS). In this
      study, we investigated the role of DJ-1 in oxidative stresses by administration
      of bisphenol A (BPA), which has been reported to induce oxidative stress in
      rodents, to male mice and cultured cells. In male mice, we found that BPA
      significantly increased the expression level of DJ-1 in the sperm and brain. In
      cultured Neuro2a and GC1 cells, we found that BPA induced ROS production and
      significantly compromised mitochondrial function concomitant with elevated
      expression and oxidization of DJ-1. DJ-1 was found to maintain the complex I
      activity against BPA-induced oxidative stress after the localization in
      mitochondria. The results showed that DJ-1 plays a role in the prevention of
      mitochondrial injury-induced cell death.

PMID- 16093528
TI  - Partly cloudy.

PMID- 16093529
TI  - Up to speed.

PMID- 16093530
TI  - Arthroscopic treatment of posterior shoulder instability: results in 33 patients.
AB  - BACKGROUND: Posterior shoulder instability is a relatively rare condition and a
      surgical challenge. Arthroscopic techniques have allowed for a potential
      improvement as well as diagnosis and management of this condition. PURPOSE: To
      evaluate the outcomes of arthroscopic posterior shoulder stabilization and to
      evaluate preoperative and intraoperative variables as predictors of success.
      STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Thirty-three
      consecutive patients with a mean age of 25 years (range, 19-34 years) who
      underwent posterior arthroscopic shoulder stabilization with suture anchors
      (mean, 3 anchors) or suture capsulolabral plication (mean, 5.3 stitches) or both
      were reviewed at a mean follow-up of 39.1 months (range, 22-60 months). Shoulder
      outcomes rating scores were determined using the American Shoulder and Elbow
      Surgeons Rating Scale, the Western Ontario Shoulder Instability Index, the
      Subjective Patient Shoulder Evaluation, and the Single Assessment Numeric
      Evaluation. RESULTS: There were 7 failures: 4 for recurrent instability and 3 for
      symptoms of pain. Overall, outcomes scores demonstrated mean values of the
      American Shoulder and Elbow Surgeons Rating Scale of 94.6, Subjective Patient
      Shoulder Evaluation of 20.0, Western Ontario Shoulder Instability Index of 389.4
      (81.5% of normal), and Single Assessment Numeric Evaluation of 87.5. Patients
      with voluntary instability demonstrated worse outcomes (P = .025), and those with
      prior surgery of the shoulder also did worse (P = .02). CONCLUSION: Arthroscopic
      treatment of posterior shoulder instability is an effective means to improve
      symptoms associated with recurrent posterior subluxation of the shoulder. It can
      provide predictable success in the setting of unidirectional, nonvoluntary
      posterior instability without prior surgery.

PMID- 16093531
TI  - Trochlear contact pressures after anteromedialization of the tibial tubercle.
AB  - BACKGROUND: Anteromedialization is recommended for cartilage restoration of
      patellofemoral defects, with the presumption that it decreases contact pressures
      across the trochlea. No study has evaluated pressures on the trochlear side of
      the patellofemoral joint after anteromedialization of the tibial tubercle.
      HYPOTHESIS: Anteromedialization of the tibial tubercle decreases contact pressure
      across the trochlea. STUDY DESIGN: Controlled laboratory study. METHODS: Ten
      cadaveric knees were tested by placing an electroresistive pressure sensor on the
      femoral side of the patellofemoral joint. A validated model of nonweightbearing
      resisted extension was simulated by loading the extensor mechanism at 89.1 N and
      178.2 N. Knees were tested 3 times per load at 30 degrees , 60 degrees , 90
      degrees , and 105 degrees . The center of force and pressure across the
      patellofemoral articulation were compared before and after a reproducible and
      consistent anteromedialization. RESULTS: The mean center of force shifted
      medially after anteromedialization at 89.1 N and 178.2 N. At 89.1 N, the mean
      total contact pressure decreased significantly (P < .05) at all angles, and at
      178.2 N, it decreased significantly at 30 degrees , 60 degrees , and 90 degrees
      of knee flexion. The mean lateral trochlear contact pressure decreased
      significantly (P < .05) at all flexion angles at both 89.1 N and 178.2 N. The
      mean central trochlear contact pressure decreased significantly (P < .05) at 30
      degrees with the 89.1-N and 178.2-N loads but increased significantly (P < .05)
      at 90 degrees with the 89.1-N load. The mean medial trochlear contact pressure
      increased significantly (P < .05) at all flexion angles at 89.1 N and 178.2 N.
      CONCLUSION: Anteromedialization shifts the contact force to the medial trochlea
      and decreases the mean total contact pressure. CLINICAL RELEVANCE:
      Anteromedialization decreases the mean total contact pressure while shifting
      contact pressure toward the medial trochlea. This study suggests that
      anteromedialization is appropriate for unloading the lateral trochlea. However,
      this procedure appears to have minimal benefit on central chondral defects, and
      it may actually increase the load in patients with medial defects.

PMID- 16093532
TI  - Tendon-bone interface motion in transosseous suture and suture anchor rotator
      cuff repair techniques.
AB  - BACKGROUND: Although many studies involving rotator cuff repair fixation have
      focused on ultimate fixation strength and ability to restore the tendon's native
      footprint, no studies have characterized the stability of the repair with regard
      to motion between the tendon and repair site footprint. HYPOTHESIS: Suture anchor
      fixation for rotator cuff repair has greater interface motion between tendon and
      bone than does transosseous suture fixation. STUDY DESIGN: Controlled laboratory
      study. METHODS: Twelve fresh-frozen human cadaveric shoulders were tested in a
      custom device to position the shoulder in internal and external rotations with
      simulated supraspinatus muscle loading. Tendon motion relative to the insertional
      footprint on the greater tuberosity was determined optically using a digital
      camera rigidly connected to the humerus, with the humerus positioned at 60
      degrees of internal rotation and 60 degrees of external rotation. Testing was
      performed for the intact tendon, a complete supraspinatus tear, a suture anchor
      repair, and a transosseous tunnel repair. RESULTS: Difference in tendon-bone
      interface motion when compared with the intact tendon was 7.14 +/- 3.72 mm for
      the torn rotator cuff condition, 2.35 +/- 1.26 mm for the suture anchor repair,
      and 0.02 +/- 1.18 mm for the transosseous suture repair. The transosseous suture
      repair demonstrated significantly less motion when compared with the torn rotator
      cuff and suture anchor repair conditions (P < .05). CONCLUSION: Transosseous
      suture repair compared with suture anchor repair demonstrated superior tendon
      fixation with reduced motion at the tendon-to-tuberosity interface. CLINICAL
      RELEVANCE: Development of new fixation techniques for arthroscopic and open
      rotator cuff repairs should attempt to minimize interface motion of the tendon
      relative to the tuberosity.

PMID- 16093533
TI  - Arthroscopic transtendon repair of partial-thickness articular-side tears of the
      rotator cuff: anatomical and clinical study.
AB  - BACKGROUND: The precise results of arthroscopic transtendon repair of partial
      thickness articular-side tears of the rotator cuff remain to be reported.
      HYPOTHESIS: Arthroscopic transtendon repair is useful in patients with Ellman
      grade 3 (>6 mm) partial-thickness articular-side tears of the supraspinatus
      tendon. STUDY DESIGN: Descriptive laboratory study and case series; Level of
      evidence, 4. METHODS: In 43 cadaveric shoulders (mean age, 80 years; range, 50-97
      years), the authors measured the width of the supraspinatus insertion (medial-to
      lateral direction) and the distance between the articular cartilage edge and the
      tendon insertion at a site 10 mm lateral to the anterior margin of the greater
      tuberosity. A clinical study group of 17 patients (mean age, 42 years; range, 17
      51 years) was observed for a mean follow-up of 39 months (range, 25-57 months).
      University of California at Los Angeles and Japanese Orthopaedic Association
      shoulder scores and postoperative overhead athletic activities were evaluated.
      RESULTS: The mean width of the supraspinatus insertion was 9.6 mm (SD, 1.6 mm;
      range, 7-13 mm; 95% confidence interval, 9.1-10.1 mm; 95% prediction interval,
      6.4-12.8 mm). The mean distance between the articular cartilage edge and the
      tendon insertion was 0.3 mm (range, 0-2 mm). After the procedure, the mean
      University of California at Los Angeles and Japanese Orthopaedic Association
      scores significantly improved from 17.3 and 68.4 points to 32.9 and 94.8 points,
      respectively (P < .01). Rated on the Japanese Orthopaedic Association scale,
      results were excellent in 14, good in 2, and fair in 1 patient; there were no
      poor results. Of 6 overhead-throwing athletes, 2 returned to their previous
      sports at the same level, 3 returned at a lower level, and 1 was unable to
      return. CONCLUSION: Arthroscopic transtendon repair is a safe, reliable procedure
      in patients with grade 3 partial-thickness articular-side tears. In the majority
      of patients, partial tears of more than 6 mm of the supraspinatus tendon
      thickness involved more than 50% of the entire tendon thickness.

PMID- 16093534
TI  - Revision anterior cruciate ligament reconstruction using a 2-stage technique with
      bone grafting of the tibial tunnel.
AB  - BACKGROUND: Revision anterior cruciate ligament surgery is often considered a
      salvage procedure with limited goals. However, this limitation need not be the
      case. Similar to primary reconstruction, the goal should be to choose an
      appropriate graft and place it in an anatomical position in a good quality bone.
      The issue of good quality bone seems to have been ignored. HYPOTHESIS: A 2-stage
      anterior cruciate ligament revision reconstruction with bone grafting of the
      tibial tunnel and the use of a different femoral tunnel will produce measured
      knee laxity and International Knee Documentation Committee scores similar to a
      primary anterior cruciate ligament reconstruction. STUDY DESIGN: Case control
      study; Level of evidence, 3. METHODS: This prospective study involved 49
      consecutive 2-stage anterior cruciate ligament revisions (group R) performed by a
      single surgeon from 1993 to 2000. Two-stage revision surgery was performed if the
      tibial tunnel from a previous reconstruction surgery would overlap (either
      partially or fully) the correctly placed revision tunnel. The first stage
      consisted of removal of the old graft and interfering metalwork, together with
      bone grafting of the tibial tunnel. After ensuring adequate bone graft
      incorporation using computed tomography scan, the second stage revision was
      undertaken. This stage comprised harvesting the autograft, its anatomical
      placement, and its adequate fixation. The results were compared with the results
      of a matched group of patients with primary anterior cruciate ligament
      reconstruction (group P). RESULTS: In group R, as meniscal and chondral lesions
      were more common, the International Knee Documentation Committee scores were
      lower than those of group P (61.2 for group R and 72.8 for group P; P = .006).
      Objective laxity measurement was similar in both groups (1.36 mm for group R and
      1.2 mm for group P; P = .25). CONCLUSION: This study establishes that the laxity
      measurements achieved with a 2-stage revision anterior cruciate ligament
      reconstruction can be similar to those achieved after primary anterior cruciate
      ligament reconstruction, although the International Knee Documentation Committee
      rating is lower.

PMID- 16093535
TI  - Articular cartilage repair in soccer players with autologous chondrocyte
      transplantation: functional outcome and return to competition.
AB  - BACKGROUND: The ability of autologous chondrocyte transplantation to produce and
      maintain an effective articular cartilage repair under high mechanical demands
      has not been investigated. HYPOTHESIS: Autologous chondrocyte transplantation
      provides a reliable and durable repair of full-thickness knee articular cartilage
      lesions in high-demand athletes. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: A total of 45 soccer players were evaluated 41 +/- 4 months after
      autologous chondrocyte transplantation for their ability to return to soccer, the
      timing of their return, skill level, and functional outcome rating by the Tegner
      activity rating scale score and Brittberg score. The factors influencing the
      return to sport were analyzed. RESULTS: Of these players, 72% reported good to
      excellent results, with significant overall improvement of Tegner activity rating
      scale scores; 33% returned to soccer, including 83% of competitive-level players
      and 16% of recreational players. Of the returning players, 80% returned to the
      same skill level and 87% maintained their ability to play soccer at 52 +/- 8
      months postoperatively. Players who successfully returned to soccer were
      significantly younger and had a shorter preoperative duration of symptoms than
      did patients who did not return to the sport. Concomitant adjuvant procedures did
      not adversely affect the ability to return to soccer. CONCLUSION: Repair of knee
      articular cartilage lesions by autologous chondrocyte transplantation in high
      performance athletes is particularly successful in younger, competitive athletes
      with limited preoperative intervals.

PMID- 16093536
TI  - Anatomical acromioclavicular ligament reconstruction: a biomechanical comparison
      of reconstructive techniques of the acromioclavicular joint.
AB  - BACKGROUND: Current surgical treatments for acromioclavicular separations do not
      re-create the anatomy of the acromioclavicular joint. HYPOTHESIS: Anatomical
      acromioclavicular reconstruction re-creates the strength of the native
      acromioclavicular joint and is stronger than a modified Weaver-Dunn repair. STUDY
      DESIGN: Controlled laboratory study. METHODS: The native acromioclavicular joint
      in 6 fresh-frozen cadaveric upper extremities was stressed to failure under
      uniaxial tension in the coronal plane. A modified Weaver-Dunn procedure,
      anatomical acromioclavicular reconstruction using a palmaris longus graft, and
      anatomical acromioclavicular reconstruction using a flexor carpi radialis graft
      were then performed sequentially. Each repair was stressed to failure. Load
      displacement curves and mechanism of failure were recorded for each. RESULTS:
      Loads at failure for the native acromioclavicular joint complex, modified Weaver
      Dunn procedure, anatomical acromioclavicular reconstruction using a palmaris
      longus tendon graft, and anatomical acromioclavicular reconstruction using a
      flexor carpi radialis tendon graft were 815 N, 483 N, 326 N, and 774 N,
      respectively. The strength of the native acromioclavicular joint complex was
      significantly different from the modified Weaver-Dunn repair (P < .001) and the
      anatomical acromioclavicular reconstruction using a palmaris longus tendon graft
      (P < .001) but not from the anatomical acromioclavicular reconstruction using a
      flexor carpi radialis tendon graft (P = .607). CONCLUSION: The strength of the
      described anatomical acromioclavicular reconstruction is limited by the tendon
      graft used. Anatomical acromioclavicular reconstruction with a flexor carpi
      radialis tendon graft re-creates the tensile strength of the native
      acromioclavicular joint complex and is superior to a modified Weaver-Dunn repair.

PMID- 16093537
TI  - Lumbar spondylolysis in pediatric and adolescent soccer players.
AB  - BACKGROUND: Lumbar spondylolysis in young soccer players has not been studied
      extensively. PURPOSE: The purpose of this study was to review lumbar
      spondylolysis in young soccer players, describe the causes, and report the
      results of nonoperative treatment emphasizing the cessation of activity for 3
      months. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The authors
      reviewed 57 child and adolescent soccer players (35 boys and 22 girls) with
      lumbar spondylolysis who came to their outpatient clinic for back pain
      evaluation. These patients received different modalities of nonoperative
      treatment, including cessation of sports and wearing a thoracolumbosacral
      orthosis. Soccer skills, field position, side of dominant leg, age, initiating
      event of low back pain, duration of symptoms, and nonoperative treatment were
      reviewed. Clinical outcome of treatment was assessed by the Steiner-Micheli
      criteria at the most recent follow-up (minimum 2 years). The Fisher exact test
      was used to compare all the data. RESULTS: Of the patients, 43% noticed that pain
      started after a high-velocity kick. Thirty-three (58%) of 57 patients had
      excellent results with no pain during sports, 20 (35%) good, 3 (5%) fair, and 1
      (2%) poor. Subjects who ceased playing soccer for 3 months had better results
      than those who did not comply with this restriction. CONCLUSION: The authors
      recommend stopping sports for at least 3 months in cases of lumbar spondylolysis
      in young soccer players who hope to return to their previous level of play
      without back pain.

PMID- 16093538
TI  - Suture plication, thermal shrinkage, and sclerosing agents: effects on rat
      patellar tendon length and biomechanical strength.
AB  - BACKGROUND: Shortening or tightening of dense, collagenous tissues is often
      desirable in the treatment of laxity. PURPOSE: To compare the effect of stress
      protection suture, radiofrequency thermal shrinkage combined with stress
      protection suture, and a 5% sodium morrhuate sclerosing injection on the length
      and biomechanical strength of the rat patellar tendon. HYPOTHESIS: Sclerosing
      agents will increase tendon mechanical strength. Thermal shrinkage combined with
      stress-protection suture and stress-protection suture only will cause a short
      term decrease in tendon strength. All 3 methods will produce equivalent
      shortening of the tendon. STUDY DESIGN: Controlled laboratory study. METHODS:
      Forty-six female retired breeder rats were split into 4 groups, each receiving 1
      of the 3 aforementioned treatments plus a control group that received a saline
      injection. After 4 weeks' survival, the length and biomechanical properties of
      the patellar tendons were measured and compared to the contralateral untreated
      tendon. RESULTS: Rats treated with stress-protection suture had shorter tendons.
      Radiofrequency thermal shrinkage combined with stress-protection suture yielded
      tendons that were both shorter and stronger than were the untreated contralateral
      tendons. The sodium morrhuate-injected tendons were stronger whereas the saline
      treated tendons were weaker than were their respective untreated contralateral
      tendons. CONCLUSION: Surgical stress-protection suture without radiofrequency
      shrinkage is most effective at shortening the length of the rat patellar tendon,
      whereas radiofrequency thermal shrinkage combined with stress-protection suture
      as well as sodium morrhuate are effective at increasing the strength of rat
      patellar tendons. CLINICAL RELEVANCE: Judicious use of thermal shrinkage in
      combination with stress protection may improve ligament strength and decrease
      laxity.

PMID- 16093539
TI  - Impact of measurement error in the analysis of bone tunnel enlargement after
      anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Radiographic bone tunnel enlargement after anterior cruciate ligament
      reconstruction is frequently reported. The error associated with measuring
      tunnels on radiographs has not been established and may be substantial.
      HYPOTHESIS: Measurement error influences interpretation of bone tunnel
      enlargement. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 2.
      METHODS: Radiographs and clinical outcomes were obtained from 76 subjects who had
      undergone hamstring tendon anterior cruciate ligament reconstruction. Tunnel
      enlargement was determined by measuring the widths of the femoral and tibial
      tunnels with a digital caliper in lateral and anteroposterior radiographs.
      Measurements were corrected for magnification; the percentage change in tunnel
      widths was recorded relative to the diameters drilled at surgery. One examiner
      measured all radiographs and repeated the procedure for 20 randomly selected
      radiographs 12 months later. A second examiner measured the same 20 radiographs.
      Intraclass correlation coefficients and 95% confidence intervals for intrarater
      and interrater measurement errors were calculated. Confidence intervals were used
      to divide subjects into 2 groups according to whether bone tunnel enlargement was
      within (unenlarged tunnel group) or greater than (enlarged tunnel group) the 95%
      confidence interval for measurement error; clinical comparisons between these
      groups were made for each view of tibial and femoral tunnels. RESULTS:
      Measurement errors for tunnel enlargement ranged from 17% to 26% for intrarater
      measurements and 24% to 38% for interrater measurements. For the lateral view of
      the tibial tunnel, there was a significant positive association between tunnel
      enlargement and anterior knee laxity. There was no relationship between femoral
      tunnel enlargement and anterior knee laxity. CONCLUSION: There was considerable
      error associated with bone tunnel measurement. A relationship between tibial
      tunnel enlargement on the lateral radiograph and anterior knee laxity was evident
      once enlargement was defined as a change that exceeded measurement error.
      CLINICAL RELEVANCE: Measurement of bone tunnels on radiographs is useful for
      interpreting large changes; caution should be used when small changes are
      observed.

PMID- 16093540
TI  - Biochemical and biomechanical properties of lesion and adjacent articular
      cartilage after chondral defect repair in an equine model.
AB  - BACKGROUND: Chondral defects may lead to degradative changes in the surrounding
      cartilage, predisposing patients to developing osteoarthritis. PURPOSE: To
      quantify changes in the biomechanical and biochemical properties of the articular
      cartilage adjacent to chondral defects after experimental defect repair. STUDY
      DESIGN: Controlled laboratory study. METHODS: Specimens were harvested from
      tissue within (lesion), immediately adjacent to, and at a distance from (remote
      area) a full-thickness cartilage defect 8 months after cartilage repair with
      genetically modified chondrocytes expressing insulin-like growth factor-I or
      unmodified, control chondrocytes. Biomechanical properties, including
      instantaneous Young's and equilibrium aggregate moduli, were determined by
      confined compression testing. Biochemical properties, such as water and
      proteoglycan content, were also measured. RESULTS: The instantaneous Young's
      modulus, equilibrium modulus, and proteoglycan content increased, whereas water
      content decreased with increasing distance from the repaired lesion. The
      instantaneous Young's and equilibrium moduli of the adjacent articular cartilage
      were 80% and 50% that of remote area samples, respectively, whereas water content
      increased 0.9% and proteoglycan content was decreased by 35%. No significant
      changes in biomechanical and biochemical properties were found either in the
      lesion tissue or in adjacent cartilage with genetic modification of the
      chondrocytes. CONCLUSION: Articular cartilage adjacent to repaired chondral
      defects showed significant remodeling 8 months after chondral defect repair,
      regardless of whether genetically modified or unmodified cells were implanted.
      CLINICAL RELEVANCE: Changes in the biochemical and biomechanical properties of
      articular cartilage adjacent to repaired chondral defects may represent
      remodeling as part of an adaptive process or degeneration secondary to an altered
      distribution of joint forces. Quantification of these changes could provide
      important parameters for assessing progress after operative chondral defect
      repair.

PMID- 16093541
TI  - Biomechanics of the shoulder in youth baseball pitchers: implications for the
      development of proximal humeral epiphysiolysis and humeral retrotorsion.
AB  - BACKGROUND: The effects of repetitive throwing on the shoulders of developing
      athletes are not well understood because of the paucity of data describing the
      biomechanics of youth pitchers and the plasticity of the developing skeleton.
      HYPOTHESIS: The direction and magnitude of the stresses that exist at the
      proximal humeral physis during the fastball pitching motion are consistent with
      the development of proximal humeral epiphysiolysis (Little League shoulder)
      and/or humeral retro-torsion. STUDY DESIGN: Descriptive laboratory study.
      METHODS: A total of 14 elite youth baseball pitchers (mean age, 12.1 +/- 0.4
      years) were filmed from the front and dominant side while throwing fastballs in a
      simulated game. The net force and torque acting on the humerus throughout the
      throwing motion were calculated using standard biomechanical techniques. RESULTS:
      The external rotation torque about the long axis of the humerus reached a peak
      value of 17.7 +/- 3.5 N.m (2.7% +/- 0.3% body weight x height) just before
      maximum shoulder external rotation. A shoulder distraction force of 214.7 +/-
      47.2 N (49.8% +/- 8.3% body weight) occurred at, or just after, ball release.
      CONCLUSION: Shear stress arising from the high torque late in the arm-cocking
      phase is large enough to lead to deformation of the weak proximal humeral
      epiphyseal cartilage, causing either humeral retrotorsion or proximal humeral
      epiphysiolysis over time. The stresses generated by the external rotation torque
      are much greater than those caused by distraction forces generated during the
      pitching motion of youth baseball pitchers. CLINICAL RELEVANCE: The motion of
      throwing fastballs by youth baseball pitchers results in force components
      consistent with proposed mechanisms for 2 clinical entities.

PMID- 16093542
TI  - Broken bioabsorbable femoral cross-pin after anterior cruciate ligament
      reconstruction with hamstring tendon graft: a case report.

PMID- 16093543
TI  - Autologous chondrocyte implantation versus debridement for treatment of full
      thickness chondral defects of the knee: an observational cohort study with 3-year
      follow-up.
AB  - BACKGROUND: Studies that compare the effectiveness of different cartilage repair
      treatments are needed to update treatment algorithms. HYPOTHESIS: Autologous
      chondrocyte implantation provides greater improvement in overall condition score
      than does debridement at a minimum of 3 years' follow-up. STUDY DESIGN: Cohort
      study; Level of evidence, 3. METHODS: Cohorts for debridement and autologous
      chondrocyte implantation each included 58 Cartilage Repair Registry patients who
      met study criteria. A retrospective analysis was performed on prospectively
      collected baseline and follow-up data. RESULTS: Patients in the autologous
      chondrocyte implantation and debridement groups had similar demographics and
      chondral lesions at baseline. However, more autologous chondrocyte implantation
      patients failed a previous debridement or marrow stimulation procedure than did
      debridement patients. Follow-up outcome assessments were completed by 54
      autologous chondrocyte implantation patients and 42 debridement patients. Eighty
      one percent of the autologous chondrocyte implantation patients and 60% of the
      debridement patients reported median improvements of 5 points and 2 points,
      respectively, in the overall condition score. Autologous chondrocyte implantation
      patients also reported greater improvements in the median pain and swelling
      scores than did debridement patients. The treatment failure rate was the same for
      both autologous chondrocyte implantation and debridement patients. Eighteen
      autologous chondrocyte implantation patients and 1 debridement patient had at
      least 1 subsequent operation. CONCLUSION: Although patients treated with
      debridement for symptomatic, large, focal, chondral defects of the distal femur
      had some functional improvement at follow-up, patients who received autologous
      chondrocyte implantations obtained higher levels of knee function and had greater
      relief from pain and swelling at 3 years.

PMID- 16093544
TI  - Knee stability after articulated external fixation.
AB  - BACKGROUND: Articulated external fixation has been proposed as a method to
      protect ligament reconstructions while allowing aggressive and early
      postoperative rehabilitation after knee dislocation. However, the ability of
      these fixators to protect and stabilize the knee joint has not been clearly
      determined. HYPOTHESIS: Articulated external fixation can reduce anteroposterior
      translation in the cruciate-deficient knee and reduce cruciate ligament strain in
      cases of intact or reconstructed ligaments. STUDY DESIGN: Controlled laboratory
      study. METHODS: Knee stability was assessed by 3 standard clinical stability
      tests (Lachman, anterior drawer, and posterior drawer) on 7 human cadaveric lower
      extremities. Instrumented forces of 100 N were applied to the tibia to measure
      cruciate ligament forces and tibiofemoral displacement in intact and cruciate
      deficient specimens with and without articulated external fixation to determine
      the degree to which a fixator can protect cruciate ligaments and stabilize the
      knee. Articulated external fixation was applied using monolateral and bilateral
      fixators to comparatively analyze the effectiveness of each construct.
      Statistical analysis was performed using 2-tailed, paired Student t tests.
      RESULTS: Application of the monolateral articulated external fixator to specimens
      with intact ligaments significantly reduced cruciate ligament forces by 1.0 N (P
      = .011), 1.7 N (P = .046), and 1.4 N (P = .009) for Lachman, anterior drawer, and
      posterior drawer tests, respectively. In the cruciate ligament-deficient knees,
      the application of a monolateral fixator significantly reduced tibiofemoral
      translation by 49%, 70%, and 46% for Lachman, anterior drawer, and posterior
      drawer tests, respectively. No significant differences between the monolateral
      and bilateral fixator frames, in terms of ligament protection and joint
      stabilization, were observed. CONCLUSION AND CLINICAL RELEVANCE: Articulated
      external fixation of the knee can reduce stress in the cruciate ligaments after
      multiligament reconstructions and can decrease anteroposterior translation in the
      cruciate-deficient knee.

PMID- 16093545
TI  - Multirater agreement of arthroscopic grading of knee articular cartilage.
AB  - BACKGROUND: Acute and chronic cartilage injury of the knee has an important
      impact on prognosis. The validity of the classification of such injuries is
      critical for prospective multicenter studies. The agreement among multiple
      surgeons at different institutions for articular cartilage lesions has not been
      established. HYPOTHESIS: Arthroscopic classification of articular cartilage
      lesions is reliable and reproducible and can be used for multicenter studies
      involving multiple surgeons. STUDY DESIGN: Cohort study (diagnosis); Level of
      evidence, 1. METHODS: A total of 6 surgeons from 5 centers reviewed 31 videos of
      articular cartilage lesions. With grade 2 and grade 3 combined for the analysis,
      observed agreement ranged from 81% to 94%, and kappa ranged from 0.34 to 0.87. An
      additional 22 videos comprising grade 2 and grade 3 lesions were analyzed, and
      the observed agreement was 80%, with an overall kappa of 0.47. CONCLUSION:
      Arthroscopic grading of articular cartilage lesions is reproducible among
      surgeons at different centers. CLINICAL RELEVANCE: Articular cartilage lesions
      can be reliably classified among surgeons at different sites. Such reliability is
      important for multicenter clinical research studies involving arthroscopic knee
      surgery.

PMID- 16093546
TI  - Injuries in female soccer players: a prospective study in the German national
      league.
AB  - BACKGROUND: In contrast to the high number of studies about soccer injuries in
      men, epidemiologic data in high-level female soccer players are scarce. PURPOSE:
      Analysis of injury incidence in elite female soccer players. STUDY DESIGN:
      Descriptive epidemiology study. METHODS: There were 165 female soccer players
      (age, 22.4 +/- 5.0 years) from 9 teams competing in the German national league,
      who were followed for one complete outdoor season. Their trainers documented the
      exposure to soccer on a weekly basis for each player, and the team physical
      therapists reported all injuries with regard to location, type, and circumstances
      of occurrence. An injury was defined as any physical complaint associated with
      soccer that limited sports participation for at least 1 day. RESULTS: There were
      241 injuries sustained by 115 players (70%) reported; 39 injuries (16%) were
      owing to overuse, and 202 injuries (84%) were traumatic. Overall, 42% of the
      traumatic injuries occurred during training (2.8/1000 hours of training; 95%
      confidence interval, 2.2-3.4) and 58% during matches (23.3/1000 match hours; 95%
      confidence interval, 19.1-27.5); 102 of the traumatic injuries were caused by a
      contact situation, whereas 95 occurred without any contact. Most injuries (80%)
      were located at the lower extremities, concerning mainly the thigh (n = 44), knee
      (n = 45), and ankle (n = 43). Ankle sprain (n = 37) was the most often diagnosed
      injury. There were 51% minor injuries, 36% moderate injuries, and 13% major
      injuries. Eleven anterior cruciate ligament ruptures were observed during the
      season. CONCLUSION: The results revealed a high injury incidence rate in games as
      well as a comparably low incidence rate during training. An important finding of
      this investigation was the frequent occurrence of anterior cruciate ligament
      ruptures. Preventive measures should thus focus on the high prevalence of
      anterior cruciate ligament tears, mostly occurring in noncontact situations.

PMID- 16093547
TI  - Symptomatic superior labral anterior posterior lesion with absence of the long
      head of the biceps tendon: a case report.

PMID- 16093549
TI  - Computer identification of snoRNA genes using a Mammalian Orthologous Intron
      Database.
AB  - Based on comparative genomics, we created a bioinformatic package for computer
      prediction of small nucleolar RNA (snoRNA) genes in mammalian introns. The core
      of our approach was the use of the Mammalian Orthologous Intron Database (MOID),
      which contains all known introns within the human, mouse and rat genomes. Introns
      from orthologous genes from these three species, that have the same position
      relative to the reading frame, are grouped in a special orthologous intron table.
      Our program SNO.pl searches for conserved snoRNA motifs within MOID and reports
      all cases when characteristic snoRNA-like structures are present in all three
      orthologous introns of human, mouse and rat sequences. Here we report an example
      of the SNO.pl usage for searching a particular pattern of conserved C/D-box
      snoRNA motifs (canonical C- and D-boxes and the 6 nt long terminal stem). In this
      computer analysis, we detected 57 triplets of snoRNA-like structures in three
      mammals. Among them were 15 triplets that represented known C/D-box snoRNA genes.
      Six triplets represented snoRNA genes that had only been partially characterized
      in the mouse genome. One case represented a novel snoRNA gene, and another three
      cases, putative snoRNAs. Our programs are publicly available and can be easily
      adapted and/or modified for searching any conserved motifs within mammalian
      introns.

PMID- 16093548
TI  - Differential and collaborative actions of Rad51 paralog proteins in cellular
      response to DNA damage.
AB  - Metazoan Rad51 plays a central role in homologous DNA recombination, and its
      activity is controlled by a number of Rad51 cofactors. These include five Rad51
      paralogs, Rad51B, Rad51C, Rad51D, XRCC2 and XRCC3. We previously hypothesized
      that all five paralogs participate collaboratively in repair. However, this idea
      was challenged by the biochemical identification of two independent complexes
      composed of either Rad51B/C/D/XRCC2 or Rad51C/XRCC3. To investigate if this
      biochemical finding is matched by genetic interactions, we made double mutants in
      either the same complex (rad51b/rad51d) or in both complexes (xrcc3/rad51d). In
      agreement with the biochemical findings the double deletion involving both
      complexes had an additive effect on the sensitivity to camptothecin and
      cisplatin. The double deletion of genes in the same complex, on the other hand,
      did not further increase the sensitivity to these agents. Conversely, all mutants
      tested displayed comparatively mild sensitivity to gamma-irradiation and
      attenuated gamma-irradiation-induced Rad51 foci formation. Thus, in accord with
      our previous conclusion, all paralogs appear to collaboratively facilitate Rad51
      action. In conclusion, our detailed genetic study reveals a complex interplay
      between the five Rad51 paralogs and suggests that some of the Rad51 paralogs can
      separately operate in later step of homologous recombination.

PMID- 16093550
TI  - GANA--a genetic algorithm for NMR backbone resonance assignment.
AB  - NMR data from different experiments often contain errors; thus, automated
      backbone resonance assignment is a very challenging issue. In this paper, we
      present a method called GANA that uses a genetic algorithm to automatically
      perform backbone resonance assignment with a high degree of precision and recall.
      Precision is the number of correctly assigned residues divided by the number of
      assigned residues, and recall is the number of correctly assigned residues
      divided by the number of residues with known human curated answers. GANA takes
      spin systems as input data and uses two data structures, candidate lists and
      adjacency lists, to assign the spin systems to each amino acid of a target
      protein. Using GANA, almost all spin systems can be mapped correctly onto a
      target protein, even if the data are noisy. We use the BioMagResBank (BMRB)
      dataset (901 proteins) to test the performance of GANA. To evaluate the
      robustness of GANA, we generate four additional datasets from the BMRB dataset to
      simulate data errors of false positives, false negatives and linking errors. We
      also use a combination of these three error types to examine the fault tolerance
      of our method. The average precision rates of GANA on BMRB and the four simulated
      test cases are 99.61, 99.55, 99.34, 99.35 and 98.60%, respectively. The average
      recall rates of GANA on BMRB and the four simulated test cases are 99.26, 99.19,
      98.85, 98.87 and 97.78%, respectively. We also test GANA on two real wet-lab
      datasets, hbSBD and hbLBD. The precision and recall rates of GANA on hbSBD are
      95.12 and 92.86%, respectively, and those of hbLBD are 100 and 97.40%,
      respectively.

PMID- 16093551
TI  - Post-high-throughput screening analysis: an empirical compound prioritization
      scheme.
AB  - An empirical scheme to evaluate and prioritize screening hits from high
      throughput screening (HTS) is proposed. Negative scores are given when chemotypes
      found in the HTS hits are present in annotated databases such as MDDR and WOMBAT
      or for testing positive in toxicity-related experiments reported in TOXNET.
      Positive scores were given for higher measured biological activities, for testing
      negative in toxicity-related literature, and for good overlap when profiled
      against drug-related properties. Particular emphasis is placed on estimating
      aqueous solubility to prioritize in vivo experiments. This empirical scheme is
      given as an illustration to assist the decision-making process in selecting
      chemotypes and individual compounds for further experimentation, when confronted
      with multiple hits from high-throughput experiments. The decision-making process
      is discussed for a set of G-protein coupled receptor antagonists and validated on
      a literature example for dihydrofolate reductase inhibition.

PMID- 16093552
TI  - Development of a novel cytochrome p450 bioaffinity detection system coupled
      online to gradient reversed-phase high-performance liquid chromatography.
AB  - A high-resolution screening platform, coupling online affinity detection for
      mammalian cytochrome P450s (Cyt P450s) to gradient reversed-phase high
      performance liquid chromatography (HPLC), is described. To this end, the online
      Cyt P450 enzyme affinity detection (EAD) system was optimized for enzyme (beta-NF
      induced rat liver microsomes), probe substrate (ethoxyresorufine), and organic
      modifier (methanol or acetonitrile). The optimized Cyt P450 EAD system has first
      been evaluated in a flow injection analysis (FIA) mode with 7 known ligands of
      Cyt P450 1A1/1A2 (alpha-naphthoflavone, beta-naphthoflavone, ellipticine, 9
      hydroxy-ellipticine, fluvoxamine, caffein, and phenacetin). Subsequently, IC50
      values were online in FIA-mode determined and compared with those obtained with
      standardmicrosomal assay conditions. The IC50 values obtained with the online Cyt
      P450 EAD system agreed well with the IC50 values obtained in the standard assays.
      For high affinity ligands of Cyt P450 1A1/1A2, detection limits of 1 to 3 pmol
      injected (n=3; signal to noise [S/N]=3) were obtained. The individual inhibitory
      properties of ligands in mixtures of the ligands were subsequently investigated
      using an optimized Cyt P450 EAD system online coupled to gradient HPLC. Using the
      integrated online gradient HPLC Cyt P450 EAD platform, detection limits of 10 to
      25 pmol injected (n=1; S/N=3) were obtained for high-affinity ligands. It is
      concluded that this novel screening technology offers new perspectives for rapid
      and sensitive screening of individual compounds in mixtures exhibiting affinity
      for liver microsomal Cyt P450s.

PMID- 16093553
TI  - Development of a generic dual-reporter gene assay for screening G-protein-coupled
      receptors.
AB  - Multiple assay formats have been developed for the pharmacological
      characterization of G-protein-coupled receptors (GPCRs) and for screening orphan
      receptors. However, the increased pace of target identification and the rapid
      expansion of compound libraries present the need to develop novel assay formats
      capable of screening multiple GPCRs simultaneously. To address this need, the
      authors have developed a generic dual-reporter gene assay that can detect ligand
      activity at 2 GPCRs within the same assay. Two stable HEK293 cell lines were
      generated expressing either a firefly (Photinus) luciferase gene under the
      control of multiple cAMP-response elements (CREs) or a Renilla luciferase gene
      under the control of multiple 12-O-tetradecanoylphorbol-13-acetate (TPA)
      responsive elements (TREs). Coseeded reporter cells were used to assess ligand
      binding activity at both Galphas-and Galphaq-coupled receptors. By selectively
      coexpressing receptors with a chimeric G-protein, agonist activity was assessed
      at Galphai/o-coupled receptors in combination with either Galphas-or Galphaq
      coupled receptors. The dual-reporter gene assay was shown to be capable of
      simultaneously performing duplexed screens for a variety of agonist and/or
      antagonist combinations. The data generated from the duplexed reporter assays
      were pharmacologically relevant, and Z' factor analysis indicated the suitability
      of both agonist and antagonist screens for use in high-throughput screening.

PMID- 16093554
TI  - A liquid chromatography/mass spectrometry-based method for the selection of ATP
      competitive kinase inhibitors.
AB  - The currently approved kinase inhibitors for therapeutic uses and a number of
      kinase inhibitors that are undergoing clinical trials are directed toward the
      adenosine triphosphate (ATP) binding site of protein kinases. The 5'
      fluorosulfonylbenzoyl 5'-adenosine (FSBA) is an ATP-affinity reagent that
      covalently modifies a conserved lysine present in the nucleotide-binding site of
      most kinases. The authors have developed a liquid chromatography/mass
      spectrometry-based method to monitor binding of ATP competitive protein kinase
      inhibitors using FSBA as a nonselective activity-based probe for protein kinases.
      Their method provides a general, rapid, and reproducible means to screen and
      validate selective ATP competitive inhibitors of protein kinases.

PMID- 16093555
TI  - Homogeneous high-throughput screening assays for HIV-1 integrase 3beta-processing
      and strand transfer activities.
AB  - HIV-1 integrase (HIV-IN) is a well-validated antiviral drug target catalyzing a
      multistep reaction to incorporate the HIV-1 provirus into the genome of the host
      cell. Small molecule inhibitors of HIV-1 integrase that specifically target the
      strand transfer step have demonstrated efficacy in the suppression of virus
      propagation. However, only few specific strand transfer inhibitors have been
      identified to date, and the need to screen for novel compound scaffolds persists.
      Here, the authors describe 2 homogeneous time-resolved fluorescent resonance
      energy transfer-based assays for the measurement of HIV-1 integrase 3'-processing
      and strand transfer activities. Both assays were optimized for high-throughput
      screening formats, and a diverse library containing more than 1 million compounds
      was screened in 1536-well plates for HIV-IN strand transfer inhibitors. As a
      result, compounds were found that selectively affect the enzymatic strand
      transfer reaction over 3beta processing. Moreover, several bioactive molecules
      were identified that inhibited HIV-1 reporter virus infection in cellular model
      systems. In conclusion, the assays presented herein have proven their utility for
      the identification of mechanistically interesting and biologically active
      inhibitors of HIV-1 integrase that hold potential for further development into
      potent antiviral drugs.

PMID- 16093556
TI  - High-throughput screening of G protein-coupled receptor antagonists using a
      bioluminescence resonance energy transfer 1-based beta-arrestin2 recruitment
      assay.
AB  - In this study, the authors developed HEK293 cell lines that stably coexpressed
      optimal amounts of beta-arrestin2-Rluc and VENUS fusions of G protein-coupled
      receptors (GPCRs) belonging to both class A and class B receptors, which include
      receptors that interact transiently or stably with beta-arrestins. This allowed
      the use of a bioluminescence resonance energy transfer (BRET) 1- beta-arrestin2
      translocation assay to quantify receptor activation or inhibition. One of the
      developed cell lines coexpressing CCR5-VENUS and beta-arrestin2- Renilla
      luciferase was then used for high-throughput screening (HTS) for antagonists of
      the chemokine receptor CCR5, the primary co-receptor for HIV. A total of 26,000
      compounds were screened for inhibition of the agonist-promoted beta-arrestin2
      recruitment to CCR5, and 12 compounds were found to specifically inhibit the
      agonist-induced beta-arrestin2 recruitment to CCR5. Three of the potential hits
      were further tested using other functional assays, and their abilities to inhibit
      CCR5 agonist-promoted signaling were confirmed. This is the 1st study describing
      a BRET1-beta-arrestin recruitment assay in stable mammalian cells and its
      successful application in HTS for GPCRs antagonists.

PMID- 16093557
TI  - Quantitative cell-based high-content screening for vasopressin receptor agonists
      using transfluor technology.
AB  - The authors demonstrate the use of a simple, universal G-protein-coupled receptor
      (GPCR) assay to screen for agonists for a specific GPCR. Cells stably expressing
      a green fluorescent protein (GFP)-labeled beta-arrestin fusion protein and the
      vasopressin V2 receptor (V2R) were used in a high-content screening (HCS) assay
      to screen a small peptide library for V2R agonists. Cells were treated with the
      peptides at a final concentration of 500 nM for 30 min. Agonist stimulation
      causes V2R internalization into endosomes. GFP-beta-arrestin remains associated
      with the V2R in endosomes, resulting in a fluorescent pattern of intracellular
      spots. Assay plates were automatically imaged and quantitatively analyzed using
      an HCS imaging platform and a fast turnkey image analysis application optimized
      for detection of receptor activation and intracellular spots. Hits were further
      evaluated to determine their potency. The combination of unique biology,
      automated high-content analysis, and a powerful means of validating hits results
      in better leads.

PMID- 16093558
TI  - Evaluation of the InteraX system technology in a high-throughput screening
      environment.
AB  - The authors have developed a cell-based high-throughput screening (HTS)
      compatible assay to measure EGFR dimerization using the InteraX enzyme
      complementation technology of Applied Biosystems. The cells contain 2 chimeric
      proteins with complementing deletion mutants of the beta galactosidase enzyme,
      each fused to the extracellular and transmembrane part of EGFR. On binding of
      EGF, EGF receptor dimerizes and an active beta galactosidase is built. The
      authors used this homogeneous 384-well assay to screen about 20,000 diverse
      compounds. From 2 independent primary screen runs 239 hits were identified. For
      run 1, a mean S/B ratio of 4.26 and a mean Z' factor of 0.74 were obtained, for
      run 2 a mean S/B ratio of 3.88 and a mean Z' factor of 0.71 were obtained. After
      hit confirmation, repeated 4 times, 112 hits remained with a confirmation rate of
      48.9%. Thirty of the 112 could be identified as cytotoxic. Fifty-one of the
      remaining 82 compounds could be shown to be inhibitors of the beta galactosidase
      enzyme itself. In summary, 31 compounds remained as potential EGFR dimerization
      or EGF stimulation inhibitors. The authors conclude that the InteraX system
      technology is HTS capable and can detect small molecule inhibitors capable of
      inhibiting protein-protein interactions.

PMID- 16093559
TI  - A collagen IV matrix is required for guinea pig gastric epithelial cell
      monolayers to provide an optimal model of the stomach surface for
      biopharmaceutical screening.
AB  - The surface epithelial cells of the stomach represent a major component of the
      gastric barrier. A cell culture model of the gastric epithelial cell surface
      would prove useful for biopharmaceutical screening of new chemical entities and
      dosage forms. Primary cultures of guinea pig gastric mucous epithelial cells were
      grown on filter inserts (Transwells) for 3 days. Tight-junction formation,
      assessed by transepithelial electrical resistance (TEER) and permeability of
      mannitol and fluorescein, was enhanced when collagen IV rather than collagen I
      was used to coat the polycarbonate filter. TEER for cells grown on collagen IV
      was close to that obtained with intact guinea pig gastric epithelium in vitro.
      Differentiation was assessed by incorporation of [3H]glucosamine into
      glycoprotein and by activity of NADPH oxidase, which produces superoxide. Both of
      these measures were greater for cells grown on filters coated with collagen I
      than for cells grown on plastic culture plates, but no major difference was found
      between cells grown on collagens I and IV. The proportion of cells, which stained
      positively for mucin with periodic acid Schiff reagent, was greater than 95% for
      all culture conditions. Monolayers grown on membranes coated with collagen IV
      exhibited apically polarized secretion of mucin and superoxide, and were
      resistant to acidification of the apical medium to pH 3.0 for 30 min. A screen of
      nonsteroidal anti-inflammatory drugs revealed a novel effect of diclofenac and
      niflumic acid in reversibly reducing permeability by the paracellular route. In
      conclusion, the mucous cell preparation grown on collagen IV represents a good
      model of the gastric surface epithelium suitable for screening procedures.

PMID- 16093560
TI  - Adopting a practical statistical approach for evaluating assay agreement in drug
      discovery.
AB  - The authors assess the equivalence of 2 assays and put forward a general approach
      for assay agreement analysis that can be applied during drug discovery. Data sets
      generated by different assays are routinely compared to each other during the
      process of drug discovery. For a given target, the assays used for high
      throughput screening and structure-activity relationship studies will most likely
      differ in their assay reagents, assay conditions, and/or detection technology,
      which makes the interpretation of data between assays difficult, particularly as
      most assays are used to measure quantitative changes in compound potency against
      the target. To better quantify the relationship of data sets from different
      assays for the same target, the authors evaluated the agreement between results
      generated by 2 different assays that measure the activity of compounds against
      the same protein, ALK5. The authors show that the agreement between data sets can
      be quantified using correlation and Bland-Altman plots, and the precision of the
      assays can be used to define the expectations of agreement between 2 assays. They
      propose a scheme for addressing issues of assay data equivalence, which can be
      applied to address questions of how data sets compare during the lead
      identification and lead optimization processes in which assays are frequently
      added and changed.

PMID- 16093561
TI  - The advantages of the Ussing chamber in drug absorption studies.
AB  - By adding high concentrations of test drugs to an Ussing chamber with rat
      jejunum, we established a system that yields very high correlations between the
      rat absorption percentage and the membrane permeability, and that can accurately
      predict the absorption percentage for rats. An advantage of this technique is
      that, unlike the results obtained using Caco-2, the slope of the
      absorption/membrane-permeability curve is gentle, which facilitates a more exact
      prediction of the absorption percentage. In addition, the results obtained with
      this technique demonstrated that it could be used to evaluate the absorption
      percentage of drugs with an affinity for P-glycoprotein (P-gp), which cannot be
      assessed using Caco-2. This method also allows for cassette screening, which
      would facilitate evaluation of the contribution of P-gp to absorption in the
      small intestine. Cassette screening showed that absorption of fexofenadine was
      unaffected by combination with the P-gp substrate ketoconazole. Consistent with
      this finding, in vivo studies showed that ketoconazole did not affect the Fa Fg
      for fexofenadine, a pharmacokinetic parameter that reflects absorption and
      bioavailability in the small intestine. This confirms the usefulness of the
      Ussing chamber for cassette screening and also suggests that intestinal P-gp has
      a minimal contribution to drug absorption.

PMID- 16093562
TI  - Fully automated solid weighing workstation.
AB  - A fully automated, solid-to-solid weighing workstation (patent pending) is
      described in this article. The core of this automated process is the use of an
      electrostatically charged pipette tip to attract solid particles on its outside
      surface. The particles were then dislodged into a 1.2-mL destination vial in a
      microbalance by spinning the pipette tip. Textures of solid that could be weighed
      included powder, crystalline, liquid, and semi-solid substances. The workstation
      can pick up submilligram quantities of sample (=0.3mg) from source vials
      containing as little as 1mg. The destination vials containing the samples were
      stored in a 96-well rack to enable subsequent automated liquid handling. Using
      bovine serum albumin as test solid, the coefficient of variation of the protein
      concentration for 48 samples is less than 6%. The workstation was used
      successfully to weigh out 48 different synthetic compounds. Time required for
      automated weighing was similar to manual weighing. The use of this workstation
      reduced 90% hands-on time and thus exposure to potentially toxic compounds. In
      addition, it minimized sample waste and reduced artifacts due to the poor
      solubility of compound in solvents. Moreover, it enabled compounds synthesized in
      milligram quantities to be weighed out and tested in biological assays.

PMID- 16093563
TI  - Cholinergic action on cortical glial cells in vivo.
AB  - This study aims at understanding complex interactions between cortical neurons,
      glia and blood supply developing during the transition from slow-wave sleep to
      wakefulness. In spite of essential advances from in vitro and culture
      preparations, the basic mechanisms of glial interactions with their cellular and
      ionic environment had remained uninvestigated in vivo. Here we approach this
      issue by performing simultaneous intracellular recordings of cortical neurons and
      glia, together with measurements of cerebral blood flow (CBF), extracellular K+
      concentrations and local field potentials in both anesthetized (ketamine
      xylazine) and naturally behaving cats. Under anesthesia, cortical activation was
      elicited with electric stimulation of cholinergic nuclei (pedunculopontine
      tegmental in the brainstem and/or nucleus basalis in the basal forebrain).
      Iontophoretic application of acetylcholine on the recorded cells was also used.
      In the vast majority of cases (> 80%) glial cells were hyperpolarized during
      electric stimulation or spontaneous activation. This result was also obtained in
      all cases where iontophoresis was used or when glutamatergic kainate/quisqualate
      receptors were blocked with 6-cyano-7-nitroquinoxaline-2,3-dione. The glial
      hyperpolarization was associated with steady neuronal depolarization, increased
      CBF, lower extracellular K+ concentration, increased membrane resistance,
      decreased membrane capacitance and persistent positive DC field potentials. In
      some cases of cortical activation (< 20%), glial cells displayed sustained
      depolarizing potentials, in parallel with neuronal depolarization, decreased CBF
      and more negative DC field potentials. The above-mentioned effects of cholinergic
      activation were blocked by the muscarinic antagonist scopolamine. We propose that
      the glial response to cholinergic activation results from the balance between the
      direct hyperpolarizing action of acetylcholine and the depolarizing modulation of
      glutamate from the neighboring neurons, in addition to the modulation of the
      interglial communication pathway and/or the ionic traffic across blood vessels.

PMID- 16093564
TI  - Single neurons can induce phase transitions of cortical recurrent networks with
      multiple internal States.
AB  - Fluctuations of membrane potential of cortical neurons, referred to here as
      internal states, are essential for brain function, but little is known about how
      these internal states emerge and are maintained, or what determines transitions
      between these states. We performed intracellular recordings from hippocampal CA3
      pyramidal cells ex vivo and found that neurons display multiple and hierarchical
      internal states, which are linked to cholinergic activity and are characterized
      by several power law structures in membrane potential dynamics. Multiple
      recordings from adjacent neurons revealed that the internal states were coherent
      between neurons, indicating that the internal state of any given cell in a local
      network could represent the network activity state. Repeated stimulation of
      single neurons led over time to transitions to different internal states in both
      the stimulated neuron and neighboring neurons. Thus, single-cell activation is
      sufficient to shift the state of the entire local network. As the states shift to
      more active levels, theta- and gamma-frequency components developed in the form
      of subthreshold oscillations. State transitions were associated with changes in
      membrane conductance but were not accompanied by a change in reversal potential.
      These data suggest that the recurrent network organizes the internal states of
      individual neurons into synchronization through network activity with balanced
      excitation and inhibition, and that this organization is discrete, heterogeneous
      and dynamic in nature. Thus, neuronal states reflect the 'phase' of an active
      network, a novel demonstration of the dynamics and flexibility of cortical
      microcircuitry.

PMID- 16093565
TI  - Subfunctionalization of expression and peptide domains following the ancient
      duplication of the proopiomelanocortin gene in teleost fishes.
AB  - The proopiomelanocortin gene (POMC) encodes several bioactive peptides, including
      adrenocorticotropin hormone, alpha-, beta-, and gamma-melanocyte-stimulating
      hormone, and the opioid peptide beta-endorphin, which play key roles in
      vertebrate physiology. In the human, mouse, and chicken genomes, there is only
      one POMC gene. By searching public genome projects, we have found that Tetraodon
      (Tetraodon nigroviridis), Fugu (Takifugu rubripes), and zebrafish (Danio rerio)
      possess two POMC genes, which we called POMCalpha and POMCbeta, and we present
      phylogenetic and mapping evidence that these paralogue genes originated in the
      whole-genome duplication specific to the teleost lineage over 300 MYA. In
      addition, we present evidence for two types of subfunction partitioning between
      the paralogues. First, in situ hybridization experiments indicate that the
      expression domains of the ancestral POMC gene have been subfunctionalized in
      Tetraodon, with POMCalpha expressed in the nucleus lateralis tuberis of the
      hypothalamus, as well as in the rostral pars distalis and pars intermedia (PI) of
      the pituitary, whereas POMCbeta is expressed in the preoptic area of the brain
      and weakly in the pituitary PI. Second, POMCbeta genes have a beta-endorphin
      segment that lacks the consensus opioid signal and seems to be under neutral
      evolution in tetraodontids, whereas POMCalpha genes possess well-conserved
      peptide regions. Thus, POMC paralogues have experienced subfunctionalization of
      both expression and peptide domains during teleost evolution. The study of
      regulatory regions of fish POMC genes might shed light on the mechanisms of
      enhancer partitioning between duplicate genes, as well as the roles of POMC
      derived peptides in fish physiology.

PMID- 16093566
TI  - Geographical distribution of selected and putatively neutral SNPs in Southeast
      Asian malaria parasites.
AB  - Loci targeted by directional selection are expected to show elevated geographical
      population structure relative to neutral loci, and a flurry of recent papers have
      used this rationale to search for genome regions involved in adaptation. Studies
      of functional mutations that are known to be under selection are particularly
      useful for assessing the utility of this approach. Antimalarial drug treatment
      regimes vary considerably between countries in Southeast Asia selecting for local
      adaptation at parasite loci underlying resistance. We compared the population
      structure revealed by 10 nonsynonymous mutations (nonsynonymous single-nucleotide
      polymorphisms [nsSNPs]) in four loci that are known to be involved in
      antimalarial drug resistance, with patterns revealed by 10 synonymous mutations
      (synonymous single-nucleotide polymorphisms [sSNPs]) in housekeeping genes or
      genes of unknown function in 755 Plasmodium falciparum infections collected from
      13 populations in six Southeast Asian countries. Allele frequencies at known
      nsSNPs underlying resistance varied markedly between locations (F(ST) = 0.18
      0.66), with the highest frequencies on the Thailand-Burma border and the lowest
      frequencies in neighboring Lao PDR. In contrast, we found weak but significant
      geographic structure (F(ST) = 0-0.14) for 8 of 10 sSNPs. Importantly, all 10
      nsSNPs showed significantly higher F(ST) (P < 8 x 10(-5)) than simulated neutral
      expectations based on observed F(ST) values in the putatively neutral sSNPs. This
      result was unaffected by the methods used to estimate allele frequencies or the
      number of populations used in the simulations. Given that dense single-nucleotide
      polymorphism (SNP) maps and rapid SNP assay methods are now available for P.
      falciparum, comparing genetic differentiation across the genome may provide a
      valuable aid to identifying parasite loci underlying local adaptation to drug
      treatment regimes or other selective forces. However, the high proportion of
      polymorphic sites that appear to be under balancing selection (or linked to
      selected sites) in the P. falciparum genome violates the central assumption that
      selected sites are rare, which complicates identification of outlier loci, and
      suggests that caution is needed when using this approach.

PMID- 16093567
TI  - Phylogenomics of life-or-death switches in multicellular animals: Bcl-2, BH3
      Only, and BNip families of apoptotic regulators.
AB  - In this report, we conducted a comprehensive survey of Bcl-2 family members, a
      divergent group of proteins that regulate programmed cell death by an
      evolutionarily conserved mechanism. Using comparative sequence analysis, we found
      novel sequences in mammals, nonmammalian vertebrates, and in a number of
      invertebrates. We then asked what conclusions could be drawn from phyletic
      distribution, intron/exon structures, sequence/structure relationships, and
      phylogenetic analyses within the updated Bcl-2 family. First, multidomain members
      having a sequence pattern consistent with the conservation of the Bcl
      X(L)/Bax/Bid topology appear to be restricted to multicellular animals and may
      share a common ancestry. Next, BNip proteins, which were originally identified
      based on their ability to bind to E1B 19K/Bcl-2 proteins, form three independent
      monophyletic branches with different evolutionary history. Lastly, a set of Bcl-2
      homology 3-only proteins with unrelated secondary structures seems to have
      evolved after the origin of Metazoa and exhibits diverse expansion after
      speciation during vertebrate evolution.

PMID- 16093568
TI  - Recombination shapes the natural population structure of the hyperthermophilic
      archaeon Sulfolobus islandicus.
AB  - Although microorganisms make up the preponderance of the biodiversity on Earth,
      the ecological and evolutionary factors that structure microbial populations are
      not well understood. We investigated the genetic structure of a thermoacidophilic
      crenarchaeal species, Sulfolobus islandicus, using multilocus sequence analysis
      of six variable protein-coding loci on a set of 60 isolates from the Mutnovsky
      region of Kamchatka, Russia. We demonstrate significant incongruence among gene
      genealogies and a lack of association between alleles consistent with
      recombination rates greater than the rate of mutation. The observation of high
      relative rates of recombination suggests that the structure of this natural
      population does not fit the periodic selection model often used to describe
      populations of asexual microorganisms. We propose instead that frequent
      recombination among closely related individuals prevents periodic selection from
      purging diversity and provides a fundamental cohesive mechanism within this and
      perhaps other archaeal species.

PMID- 16093569
TI  - How not to search for isochores: a reply to Cohen et Al.
AB  - In a recent paper in these pages, Cohen et al. search for isochores in the human
      genome, based on a system of attributes that they assign to isochores. The
      putative isochores that they find and choose for presentation are almost all
      below 45% GC and cover only about 41% of the genome. Closer inspection reveals
      that the authors' methodology systematically loses GC-rich isochores because it
      does not anticipate the considerable fluctuations and corresponding long-range
      correlations that characterize mammalian DNA and that are highest in GC-rich DNA.
      Thus, they over-fragment GC-rich isochores (and also many GC-poor isochores)
      beyond recognition.

PMID- 16093570
TI  - Mosaic origin of the heme biosynthesis pathway in photosynthetic eukaryotes.
AB  - Heme biosynthesis represents one of the most essential metabolic pathways in
      living organisms, providing the precursors for cytochrome prosthetic groups,
      photosynthetic pigments, and vitamin B(12). Using genomic data, we have compared
      the heme pathway in the diatom Thalassiosira pseudonana and the red alga
      Cyanidioschyzon merolae to those of green algae and higher plants, as well as to
      those of heterotrophic eukaryotes (fungi, apicomplexans, and animals).
      Phylogenetic analyses showed the mosaic character of this pathway in
      photosynthetic eukaryotes. Although most of the algal and plant enzymes showed
      the expected plastid (cyanobacterial) origin, at least one of them
      (porphobilinogen deaminase) appears to have a mitochondrial (alpha
      proteobacterial) origin. Another enzyme, glutamyl-tRNA synthase, obviously
      originated in the eukaryotic nucleus. Because all the plastid-targeted sequences
      consistently form a well-supported cluster, this suggests that genes were either
      transferred from the primary endosymbiont (cyanobacteria) to the primary host
      nucleus shortly after the primary endosymbiotic event or replaced with genes from
      other sources at an equally early time, i.e., before the formation of three
      primary plastid lineages. The one striking exception to this pattern is
      ferrochelatase, the enzyme catalyzing the first committed step to heme and bilin
      pigments. In this case, two red algal sequences do not cluster either with the
      other plastid sequences or with cyanobacterial sequences and appear to have a
      proteobacterial origin like that of the apicomplexan parasites Plasmodium and
      Toxoplasma. Although the heterokonts also acquired their plastid via secondary
      endosymbiosis from a red alga, the diatom has a typical plastid-cyanobacterial
      ferrochelatase. We have not found any remnants of the plastidlike heme pathway in
      the nonphotosynthetic heterokonts Phytophthora ramorum and Phytophthora sojae.

PMID- 16093573
TI  - Is this reaction caused by this drug?
AB  - The case report on cotrimoxazole-induced pancreatitis by Versleijen et al. deals
      with the assessment of the probability that cotrimoxazole induced the acute
      pancreatitis: a causality assessment. In this editorial, we comment on this
      assessment from a clinical, pharmacological and epidemiological perspective.
      Moreover, the consequences of the results of the assessment are discussed.

PMID- 16093574
TI  - Mastocytosis and adverse reactions to biogenic amines and histamine-releasing
      foods: what is the evidence?
AB  - BACKGROUND: It has been suggested that normal concentrations of biogenic amines
      and 'histamine-releasing foods' may exacerbate symptoms in mastocytosis. The
      purpose of this study was to look for scientific evidence in the literature on
      diets restricted in biogenic amines and histamine-releasing foods in the
      treatment of mastocytosis. METHODS: Medline (1966 to 2004), Cinahl (1982 to 2004)
      and the Cochraine Library were searched for double-blind placebo-controlled food
      challenge (DBPCFC) studies with biogenic amines and/or histamine-releasing foods
      in mastocytosis. RESULTS: No studies employing DBPCFC with dietary biogenic
      amines or histamine-releasing foods in mastocytosis were found. Only a few in
      vitro studies in other diseases, animal studies and studies in humans in which
      histamine-releasing agents were incubated directly with duodenal tissues were
      found. One case was reported of severe adverse reactions to alcohol in
      mastocytosis, objectified by an open challenge. CONCLUSION: Despite the
      widespread belief that biogenic amines and histamine-releasing foods may cause
      allergy-like, non-IgE-mediated symptoms in certain patients, the role of diets
      restricted in biogenic amines and histamine-releasing foods in the treatment of
      mastosytosis remains hypothetical but worthy of further investigation. There is
      some evidence for adverse reactions to alcohol in mastocytosis.

PMID- 16093575
TI  - Anti-inflammatory effects of troglitazone in nondiabetic obese subjects
      independent of changes in insulin sensitivity.
AB  - BACKGROUND: Obesity is characterised by insulin resistance and by elevated levels
      of proinflammatory markers. We investigated whether, in the absence of changes in
      glucose, thiazolidinediones (TZDs) have anti-inflammatory effects and whether
      improvement of insulin sensitivity correlates with suppression of inflammatory
      markers. METHODS: We performed a randomised double-blind placebo-controlled
      crossover study with troglitazone (400 mg daily for eight weeks) in 15
      normoglycaemic obese subjects. We measured plasma high-sensitivity C-reactive
      protein (hsCRP), interleukin-6 (IL-6), leptin, tissue-type plasminogen activator
      (tPA), plasminogen activator inhibitor-1 (PAI-1) and tumour necrosis factor-alpha
      (TNF-alpha) after each of the two treatment periods and in 13 age- and sex
      matched lean individuals. RESULTS: Obese subjects were insulin resistant
      (decreased glucose infusion rate (GIR) during euglycaemic hyperinsulinaemic
      clamp) and had higher plasma levels of hsCRP, IL-6, leptin, tPA, and PAI-1
      compared with lean subjects. TNF-alpha also tended to be higher. Troglitazone
      improved insulin sensitivity (mean increase in whole body glucose uptake 23.1 +/-
      10.5% (p = 0.047)) and normalised plasma concentrations of hsCRP, tPA and TNF
      alpha, whereas it did not significantly change IL-6, leptin and PAI-1. Changes in
      GIR did not correlate with changes in inflammatory markers. CONCLUSION:
      Troglitazone induces suppression of some of the inflammatory markers that are
      elevated in normoglycaemic obese subjects. The suppression of inflammatory
      markers, however, does not correlate with improvement in insulin sensitivity,
      suggesting involvement of partially differential mechanisms in these effects of
      TZDs.

PMID- 16093576
TI  - HbA1c in healthy, pregnant women.
AB  - AIM: Congenital malformations and macrosomia in infants of women with type 1
      diabetes mellitus (DM1) still occur, even if diabetic control is considered
      'good' (i.e. HbA1c below the nonpregnant upper reference value of 6.3%). We,
      therefore, measured HbA1c in healthy, pregnant women to determine whether the
      upper reference value for pregnant women should be lower than the nonpregnant
      value. METHODS: We investigated HbA1c, measured by high-performance liquid
      chromatography (HPLC), in two groups of healthy primigravid women. Group 1 (n=30;
      30.0 +/- 5.3 (mean +/- sd) years; body mass index (BMI) before pregnancy 21.7 +/-
      5.3 kg/m2) had a gestational age of 30 weeks (34.6 +/- 2.5) pregnant. None of the
      women had diabetes in the family in the first and/or second degree. RESULTS:
      Group 1 had an HbA1c of 4.3 +/- 0.3% (range 3.9-5.0) and in group 2 the HbA1c was
      4.7 +/- 0.4% (range 3.6-5.9) (p < 0.001). No relation was found between HbA1C and
      BMI vs birth weight, corrected for gestational age, within the groups.
      CONCLUSIONS: Healthy, pregnant women had a low HbA1C, particularly in the first
      trimester of pregnancy. This might implicate that for prevention of congenital
      malformations and macrosomia in pregnant DM1 women and HbA1C should be below 5%
      in the first trimester of pregnancy and below 6% in the third trimester.

PMID- 16093577
TI  - Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD
      syndrome: introducing a vaccination provocation model.
AB  - BACKGROUND: Hyper-IgD and periodic fever syndrome (HIDS) is an hereditary
      autoinflammatory syndrome, characterised by recurrent inflammatory attacks.
      Treatment of HIDS is difficult, although simvastatin is beneficial and etanercept
      might be effective. Studying the treatment of a rare periodic syndrome is
      complicated by the varying frequency and severity of symptoms and low prevalence.
      Our aim was to develop a system of clinical observations to evaluate
      effectiveness of treatment-on-demand. METHODS: Seven fever episodes in three HIDS
      patients were monitored, with and without administration of etanercept or
      anakinra. We developed a clinical score, which includes 12 symptoms. In one
      patient, inflammatory attacks were provoked by vaccination. RESULTS AND
      CONCLUSIONS: At the onset of an attack, all patients reported a clinical score
      between 20 and 25. The score was used to quantify severity and define the end of
      an attack. Reproducible monitoring of inflammatory episodes was difficult, even
      in this pilot study. The effect of early administration of etanercept was
      variable. In one patient, a fever episode could be readily provoked within 12 to
      24 hours by vaccination. In this patient, the IL-1ra analogue anakinra was more
      successful in aborting the inflammatory attack than etanercept. We propose that
      this vaccination model will allow evaluation of treatment-on-demand in a
      controlled setting.

PMID- 16093578
TI  - Diagnostic work-up for faecal incontinence in daily clinical practice in the
      Netherlands.
AB  - BACKGROUND: To study variation in Dutch hospitals in applying diagnostic and
      treatment options for faecal incontinence. METHODS: Surgeons,
      gastroenterologists, internists and gynaecologists were contacted by phone or
      mail and requested to complete a questionnaire. The questionnaire asked for
      general information about patients with faecal incontinence, the use and
      availability of diagnostic techniques, the use of incontinence scores and
      therapeutic options. RESULTS: In total 306 specialists were contacted and data
      were collected from 203 specialists from 86 hospitals (response rate 66%). The
      most frequently applied diagnostics were sigmoidoscopy (64%), endoanal sonography
      (58%), evacuation proctography (56%) and/or anorectal manometry (51%). The choice
      seemed to be related to the availability of the techniques. Sigmoidoscopies were
      performed significantly more often in local hospitals (p < 0.001), while in
      medical academic centres significantly more endoanal MRI examinations were
      conducted (p < 0.05). The most stated treatment option was physiotherapy (90%),
      followed by dietary measures (83%), medicating (71%) and surgery (68%). However,
      in general, combinations of treatment options were used. CONCLUSIONS: A
      substantial variety exists in the diagnostic work-up of faecal incontinence. In
      general, at least one anorectal functional test and an imaging technique are the
      diagnostic techniques of choice. Pelvic floor physiotherapy is the first choice
      in conservative treatment.

PMID- 16093579
TI  - ANCA seropositivity in HIV: a serological pitfall.
AB  - In systemic vasculitis, cytoplasmic staining in ethanol-fixed neutrophilic
      granulocytes, i.e. cytoplasmic antineutrophilic cytoplasmic antibody (c-ANCA), is
      generally considered a highly significant serological marker. When a patient
      presents with upper airway or renal symptomatology and seropositivity to c-ANCA,
      a Wegener's granulomatosis is usually easily diagnosed by performing a biopsy of
      the diseased organ. However, not every ANCA-positive patient with pulmonary
      inflammation is suffering from Wegener's disease. In some cases of upper airway
      or pulmonary symptomatology, the a priori chance of having Wegener's disease is
      low despite a positive ANCA. A coincidental positivity of ANCA may then lead to
      clinicians jumping to conclusions. We present a 40-year-old man who was falsely
      suspected of having Wegener's disease because of upper airway symptomatology and
      c-ANCA positivity. Specificity analysis revealed that he was negative to
      antibodies for proteinase-3, but positive to myeloperoxidase. The potential
      serological pitfall of the supposedly specific c-ANCA is discussed.

PMID- 16093580
TI  - Recurrent pancreatitis after trimethoprim-sulfamethoxazole rechallenge.
AB  - We report a female patient who repeatedly developed pancreatitis after
      trimethoprim-sulfamethoxazole (TMP/SMX) use. During childhood she had undergone
      an ureterosigmoidostomy after which she had been on TMP/SMX 480 mg daily as
      prophylaxis for pyelonephritis for many years. The patient presented with
      abdominal pain caused by acute pancreatitis. No other cause, except for TMP/SMX
      use, could be identified. A causal relationship was confirmed by relapse of the
      pancreatitis after rechallenge. Our case is unique in demonstrating that acute
      pancreatitis related to the use of TMP/SMX may occur even after long-term
      treatment. We advise that the medication is discontinued immediately if a causal
      relationship with pancreatitis is suspected.

PMID- 16093581
TI  - A patient with prolonged vague pain in the lower abdomen following a three-day
      period with diarrhoea and vomiting.

PMID- 16093582
TI  - Global clinical performance rating, reliability and validity in an undergraduate
      clerkship.
AB  - BACKGROUND: Global performance rating is frequently used in clinical training
      despite its known psychometric drawbacks. Inter-rater reliability is low in
      undergraduate training but better in residency training, possibly because
      residency offers more opportunities for supervision. The low or moderate
      predictive validity of global performance ratings in undergraduate and residency
      training may be due to low or unknown reliability of both global performance
      ratings and criterion measures. In an undergraduate clerkship, we investigated
      whether reliability improves when raters are more familiar with students' work
      and whether validity improves with increased reliability of the predictor and
      criterion instrument. METHODS: Inter-rater reliability was determined in a
      clerkship with more student-rater contacts than usual. The in-training assessment
      programme of the clerkship that immediately followed was used as the criterion
      measure to determine predictive validity. RESULTS: With four ratings, inter-rater
      reliability was 0.41 and predictive validity was 0.32. Reliability was lower and
      validity slightly higher than similar results published for residency training.
      CONCLUSION: Even with increased student-rater interaction, the reliability and
      validity of global performance ratings were too low to warrant the usage of
      global performance ratings as individual assessment format. However, combined
      with other assessment measures, global performance ratings may lead to improved
      integral assessment.

PMID- 16093583
TI  - Inappropriate secretion of antidiuretic hormone in a patient with chronic
      inflammatory demyelinating polyneuropathy.

PMID- 16093584
TI  - Miliary tuberculosis or disseminated tuberculosis.

PMID- 16093585
TI  - Brachial-ankle pulse wave velocity.

PMID- 16093586
TI  - Syndrome of transient headache and neurological deficits with cerebrospinal fluid
      lymphocytosis: HaNDL.

PMID- 16093587
TI  - Pasteurellosis as zoonosis.

PMID- 16093588
TI  - Hereditary periodic fever syndromes: autoinflammatory diseases.

PMID- 16093589
TI  - Brachial-ankle pulse wave velocity in Japanese university students.
AB  - OBJECTIVE: Pulse wave velocity (PWV) correlates well with arterial distensibility
      and stiffness and is a useful non-invasive index to assess arteriosclerosis. The
      present study was conducted to evaluate the validity of noninvasive brachial
      ankle PWV (baPWV) measurements in overweight young adults. METHODS: Three hundred
      and fifty-three students were voluntarily enrolled (mean age: 20+/-2, 93 women
      and 260 men). The subjects were divided into three groups: normal (18.5 < or =
      body mass index (BMI) <25 n = 120), overweight (25 < or = BMI <30 n = 164) and
      obese (BMI > or = 30, n = 69). The baPWV was measured using volume
      plethymographic apparatus. RESULTS: Hypertension and hyperlipidemia were
      diagnosed in one-third of the subjects of the obese group and nonalcoholic fatty
      liver disease (NAFLD) was diagnosed in 64% of the obese group. The baPWV in male
      subjects was significantly higher in the obese group than in the overweight group
      and in the males with NAFLD than in those without NAFLD. The stepwise linear
      regression analysis showed that PWV was significantly associated with mean blood
      pressure (p < 0.001) and gamma-GTP (p = 0.03). CONCLUSION: Mean blood pressure
      was a powerful determination for baPWV in the university students. BaPWV may be
      useful to predict the initial stage of arteriosclerosis and conceivably NAFLD
      including nonalcoholic steatohepatitis (NASH) in obese young adults.

PMID- 16093590
TI  - Clinical evaluation of body fat percentage in 11,833 Japanese measured by air
      displacement plethysmograph.
AB  - OBJECTIVE: Body fat percentage is commonly used for assessing body composition.
      We investigated the body fat percentage in Japanese subjects measured by air
      displacement plethysmograph (ADP) termed BOD POD. METHODS: Cross-sectional
      clinical investigation study. PATIENTS AND MEASUREMENTS: We used data of 11,833
      Japanese subjects aged 20-79 years [body mass index (BMI): 23.2+/-3.7 kg/m2].
      Body fat percentage was evaluated by BOD POD. Anthropometric parameters such as
      height, weight, BMI, waist circumference and hip circumference were also
      measured. RESULTS: Mean values of body fat percentage measured by BOD POD were
      24.5+/-6.6% in men and 31.1+/-7.1% in women, mean values were also calculated as
      classified into aged groups in normal weight subjects. Body fat percentage was
      significantly correlated with BMI and 25.1% of men and 34.6% of women
      corresponded to 25 kg/m2 in BMI. CONCLUSION: Mean value of body fat percentage in
      normal weight Japanese subjects was revealed. In addition, the level of 25% in
      men and 35% in women corresponded to 25 kg/m2 of BMI.

PMID- 16093591
TI  - Frequency of gouty arthritis in patients with end-stage renal disease in Japan.
AB  - OBJECTIVE: The purpose of this study was to investigate gouty arthritis in
      Japanese patients with end-stage renal disease (ESRD). METHODS: Questionnaires
      plus patient interviews and reviews of medical records were used to investigate
      gouty arthritis in 493 Japanese patients with ESRD receiving maintenance
      dialysis. RESULTS: The frequency of gouty arthritis was 4.1% for female patients
      and 15.4% for male patients greater than 2 years before the start of dialysis,
      and 0.6% for female patients and 7.7% for male patients less than 2 years before
      the start of dialysis. After the start of dialysis the frequency was 3.4% for the
      first 2 years and 1.2% thereafter in male patients, but no gouty arthritis
      appeared in female patients. Although the annual number of gouty attacks was
      2.0+/-4.2 greater than 2 years before the start of dialysis, and 1.9+/-6.6 less
      than 2 years before the start of dialysis, the annual number of attacks decreased
      significantly after the start of dialysis to 0.2+/-0.7 in the first 2 years and
      0.1+/-0.6 thereafter. CONCLUSIONS: The frequency of gouty arthritis in Japanese
      patients with ESRD is similar to that of patients with hyperuricemia in the
      general population and it is decreased slightly before dialysis; however, the
      frequency decreases markedly after dialysis.

PMID- 16093592
TI  - Severe community-acquired pneumonia in an intensive care unit: risk factors for
      mortality.
AB  - OBJECTIVE: To evaluate severe community-acquired pneumonia (SCAP) patients in an
      intensive care unit (ICU) with regard to risk factors for mortality and to
      compare ICU patients with matched non-ICU patients to evaluate whether our
      judgement for ICU admission was appropriate or not. MATERIALS AND METHODS: During
      a 7-year period, all patients with CAP who were admitted to the ICU were
      examined. They underwent clinical and radiographic evaluations, and two commonly
      used severity of illness scores were also calculated using the Simplified Acute
      Physiological Score (SAPS) and the Acute Physiology and Chronic Health Evaluation
      (APACHE) II methods. To detect risk factors for ICU admission using existing
      guidelines, each study patient was matched with two patients hospitalized in a
      general medical ward. RESULTS: Seventy-two patients were identified during the
      study period. Their mean age was 72.9 years, and 35 patients (48.6%) subsequently
      died. For the univariate analysis, there were significant differences with the
      pulse rate > or = 130/min, blood urea nitrogen > or = 30 mg/dl, multilobar
      shadow, SAPS > or = 13, APACHE II > or = 23, and the occurrence of septic shock
      between the survivors and those who died. For the multivariate analysis, septic
      shock (p = 0.0005, odds ratio of 26.6) and blood urea nitrogen > or = 30 mg/dl (p
      = 0.037, odds ratio of 5.38) were associated with mortality. Regarding the
      characteristics of different clinical predictions for ICU admission, the revised
      American Thoracic Society criteria might have been the most accurate. CONCLUSION:
      Septic shock was associated with high mortality, which is a more accurate and
      higher predictor of mortality than was physical examination, laboratory or
      radiographic findings.

PMID- 16093593
TI  - Risk of falls in Alzheimer's disease: a prospective study.
AB  - OBJECTIVE: Falls are common in patients with Alzheimer's disease (AD).
      Identification of the potential risk factors and developing preventive strategies
      for falls will have a significant impact in maintaining the quality of life in
      AD. PATIENTS: Clinical follow-up of 124 (74.1+/-6.1 years, range 62-88) mild to
      moderate AD patients in an outpatient memory clinic. METHODS: Postural sway,
      cognitive function, use of neuroleptics, severity of periventricular and deep
      white matter lesions, and the presence or absence of silent brain infarctions on
      magnetic resonance imaging were assessed at baseline. RESULTS: A total of 104
      patients (84%) completed the study. Fall events were confirmed in 42.3% (44/104).
      After adjustment for age, gender, and cognitive status, a high grade of
      periventricular white matter lesions (odds ratio 8.7 [95%CI 1.5 to 51.8], p =
      0.017) and neuroleptic drug use (odds ratio 3.5 [95%CI 1.2 to 10.5], p = 0.027)
      were significantly associated with an increased risk of falls. CONCLUSION: Our
      results suggest that periventricular white matter lesions and the use of
      neuroleptics may be related to falls in mild to moderate AD. A comprehensive risk
      management of brain ischemia as well as the use of the smallest efficacious dose
      of neuroleptics in the treatment of behavioral and psychiatric symptoms of AD
      should be recommended to help reduce the risk of unexpected falls.

PMID- 16093594
TI  - Successful coronary stenting of the left anterior descending artery at the
      branching site of the targeted septal perforator immediately after percutaneous
      transluminal septal myocardial ablation in hypertrophic obstructive
      cardiomyopathy.
AB  - We report a case of simultaneous percutaneous treatment of hypertrophic
      obstructive cardiomyopathy (HOCM) and coronary artery disease. Cardiac
      catheterization revealed a left ventricular outflow tract pressure gradient
      (LVOTPG) of 130 mmHg and a significant left anterior descending artery (LAD)
      stenosis at the site of the 1st major septal branch. The LVOTPG was eliminated by
      injection of ethanol into the branch. Subsequently, a coronary stent was
      implanted in the LAD. A coil stent was selected due to possibility of repeat
      septal ablation in the future. Simultaneous treatment of HOCM and LAD stenosis is
      considered safe and effective using a coil stent.

PMID- 16093595
TI  - Takotsubo-like transient biventricular dysfunction with pressure gradients.
AB  - A 78-year-old woman was admitted to our hospital due to chest oppressive
      sensation. Admission electrocardiography revealed ST-segment elevation in I, II,
      III, aV(F) and V(2-6) leads. Left ventriculography showed apical akinesis and
      basal hyperkinesis with a pressure gradient of 60 mmHg between the left
      ventricular apex and the base. Right ventriculography also showed similar
      abnormal wall motion with a pressure gradient of 28 mmHg. Follow-up cardiac
      catheterization after 16 days showed normal wall motion with no pressure
      gradients. However, dobutamine stress (10 microg/kg/min) caused a pressure
      gradient of 60 mmHg between the left ventricular apex and the aorta.

PMID- 16093596
TI  - Hermansky-Pudlak syndrome with a novel mutation.
AB  - We report a case of Hermansky-Pudlak syndrome (HPS) with a novel mutation in the
      HPS1 gene. This case showed oculocutaneous albinism and lysosomal ceroid
      accumulation, however platelet dysfunction was not observed. Histopathological
      findings of the biopsied lung tissue were compatible with HPS. Sequencing
      analysis showed the insertion of C in the codon 178 (739 bp) of the HPS1 gene
      forming a stop codon at codon 181. To the best of our knowledge, this is a novel
      HPS1 gene mutation.

PMID- 16093597
TI  - Amelioration of extrapontine myelinolysis and reversible parkinsonism in a
      patient with asymptomatic hypopituitarism.
AB  - A 37-year-old woman with a history of transphenoidal surgery and gamma knife
      treatment for prolactinoma was admitted because of pneumoniae with hyponatremia
      (Na 109 mmol/l). After the careful correction of the serum sodium level within 15
      mmol/l/day, the patient developed parkinsonism. MRI of the brain disclosed a
      signal increase in the bilateral basal ganglias on T2-weighted images, a finding
      consistent with extrapontine myelinolysis (EPM). Interestingly, the parkinsonism
      fully disappeared after the replacement therapy of hydrocortisone for adrenal
      insufficiency due to hypopituitarism, and MRI 5 months later showed complete
      disappearance of the lesions, indicating the patient had ameliorated from the
      EPM.

PMID- 16093598
TI  - A patient of migraine-like headache with amnesia, pleocytosis and transient
      hypoperfusion of cerebral blood flow.
AB  - Pseudomigraine with pleocytosis (PMP) is an uncommon disease in Japan. The
      diagnostic criteria include at least one episode of transient neurological
      deficit accompanied or followed by migraine-like severe headache, cerebrospinal
      fluid (CSF) lymphocytosis, and normal neuroimaging. Both the etiology and the
      pathophysiology of PMP is not yet well defined. We report a 40-year-old man with
      a PMP-like syndrome. He came to our clinic because of severe throbbing headache
      and amnesia, and the examination showed CSF lymphocytosis of 23/mm3, a transient
      decrease of cerebral blood flow in the left thalamus. All the symptoms were
      completely resolved within 2 months.

PMID- 16093599
TI  - Multiple sclerosis following splenectomy as a treatment for idiopathic
      thrombocytopenic purpura.
AB  - A 27-year-old woman was admitted to our hospital with tetraparesis, dysesthesia
      and hypoesthesia of all regions below the breasts, urinary disturbance, and
      difficulty in breathing. Since age 21 idiopathic thrombocytopenic purpura (ITP)
      was diagnosed and steroid therapy was continued. At age 26, she had splenectomy
      for her ITP. On admission, steroid pulse therapy was administered with a
      tentative diagnosis of transverse myelitis. Symptoms gradually ameliorated. At
      age 29, she gradually lost her left vision, and multiple sclerosis was diagnosed
      and steroid therapy was administered, and her left vision gradually ameliorated.
      There are several reports describing other autoimmune disorders that arise after
      splenectomy. Since the spleen acts as a major pool of type 2 helper T cells, it
      is plausible that peripheral type 1 helper T cell activity may increase after
      splenectomy, promoting the development of autoimmune disorders. We considered
      there would be a close relation between splenectomy for ITP and multiple
      sclerosis in this case.

PMID- 16093600
TI  - Wegener's granulomatosis with eosinophilia.
AB  - Wegener's granulomatosis with eosinophilia both in blood and tissue samples has
      been rarely reported. A 25-year-old woman developed fever, granulomatous
      inflammation of nasal mucosa, pulmonary hemorrhage, suprascleritis, and cutaneous
      vasculitis. She showed eosinophilia in blood and biospy samples of skin, nasal
      mucosa, and lung. She was positive for proteinase 3-antineutrophil cytoplasmic
      antibody. She had no history of asthma. We diagnosed her as Wegener's
      granulomatosis with eosinophilia rather than Churg-Strauss syndrome. Her
      mucocutaneous and pulmonary lesions were successfully treated with high-dose
      corticosteroid and methotrexate, but her suprascleritis required pulsed
      cyclophosphamide.

PMID- 16093601
TI  - Chronic lung abscess with Pasteurella multocida infection.
AB  - We report a patient with chronic lung abscess due to Pasteurella multocida
      infection that may be caused by the contact with cows in his workplace. Despite
      its apparent rarity, chronic abscess due to P. multocida should be considered in
      the differential diagnosis of solitary pulmonary masses. This case report
      suggests that P. multocida infection can be potentially caused from saliva of
      cows as well as dogs or cats.

PMID- 16093602
TI  - Rapidly progressed acquired immunodeficiency syndrome dementia complex as an
      initial manifestation.
AB  - We report a patient with acquired immunodeficiency syndrome dementia complex
      (ADC) that presented human immunodeficiency virus infection as an initial
      manifestation. A 34-year-old man developed disturbance of consciousness and
      severe abulia over 3 months. The CD4 lymphocyte count was 7.9/microl, while human
      immunodeficiency virus RNA in blood amounted to 4.2 x 10(4) copies/ml. T2
      weighted magnetic resonance imaging showed diffusely high signal intensity in the
      deep white matter of both cerebral hemispheres. On the 20th hospital day, the
      patient died of sepsis caused by methicillin-resistant Staphylococcus aureus.
      Autopsy findings in the brain included increased glial cells and multinucleated
      giant cells in cerebral white matter and subcortical gray matter. These features
      were compatible with ADC.

PMID- 16093603
TI  - Causes of chronic retention of urine in the primary care setting.

PMID- 16093604
TI  - Characteristic spinal MRI findings of HIV-associated myelopathy in an AIDS
      patient.

PMID- 16093605
TI  - A Japanese case of familial Mediterranean fever with homozygosity for the pyrin
      E148Q mutation.

PMID- 16093606
TI  - Pulmonary empyema and mediastinal abscess resulting from esophageal carcinoma.

PMID- 16093607
TI  - Renal tuberculosis mimicking hydronephrosis.

PMID- 16093608
TI  - Endobronchial minute leiomyoma in a patient with malignant lymphoma.

PMID- 16093609
TI  - Chronic disseminated intravascular coagulation associated with abdominal aortic
      aneurysm.

PMID- 16093610
TI  - Brain abscess in acute myeloid leukemia.

PMID- 16093611
TI  - Brain MRI of hereditary hemorrhagic telangiectasia (HHT) with intrahepatic
      arteriovenous shunts.

PMID- 16093612
TI  - Nafamostat mesilate induces production of interleukin-12 and -18 in human
      peripheral blood mononuclear cells.
AB  - Little has been reported on the drugs inducing production of monocyte-derived
      cytokines like interleukin (IL)-18 and IL-12. We found that nafamostat mesilate
      elicits IL-12, IL-18, tumor necrosis factor-alpha and interferon-gamma
      production, and the expression of intercellular adhesion molecules-1, B7.1, B7.2,
      CD40, and CD40 ligand in human peripheral blood mononuclear cells. The cytokine
      production and adhesion molecule expression were abolished by anti-IL-12 and IL
      18 antibodies. Therefore, IL-18 and IL-12 may play roles in the significant and
      immediate effects of nafamostat mesilate.

PMID- 16093613
TI  - Mast cell tryptase stimulates DLD-1 carcinoma through prostaglandin- and MAP
      kinase-dependent manners.
AB  - We found that striptease-positive mast cells were abundant in the invasive front
      of human colon adenocarcinoma by examining 30 cases. Because tryptase has been
      suggested to be the agonist proteinase for protease-activated receptor-2 (PAR-2),
      we investigated the effects of stimulation of PAR-2 by tryptase on the cell
      signaling and proliferation of DLD-1, a human colon carcinoma cell line. PAR-2
      stimulation by tryptase induced the increase in [Ca(2+)](i), which was
      desensitized by the prior application of PAR-2 activating peptide (AP). The
      proliferative responses of DLD-1 to tryptase and PAR-2 AP were associated with
      the phosphorylation of MEK and MAP kinase. Inhibition of MEK by PD98059
      completely inhibited the proliferation-enhancing effects of tryptase and PAR-2 AP
      as well as phosphorylation of MAP kinase. Moreover, tryptase and PAR-2 AP
      stimulated the production of prostaglandin E2 and the inhibition of prostaglandin
      synthesis by indomethacin or NS398 resulted in the complete inhibition of the
      proliferative responses to tryptase and PAR-2 AP. Furthermore, the tryptase
      stimulated proliferation of DLD-1 was concentration-dependently inhibited by
      nafamostat mesilate, a specific inhibitor of tryptase. These results as a whole
      indicated that tryptase has proliferative effects on DLD-1 through cyclooxygenase
      and MAP kinase-dependent manners acting on PAR-2 by its proteolytic activity.

PMID- 16093614
TI  - Development of a hyperpolarized 129Xe system on 3T for the rat lungs.
AB  - MRI (magnetic resonance imaging) with 129Xe has gained much attention as a
      diagnostic methodology because of its affinity for lipids and possible
      polarization. The quantitative estimation of net detectability and stability of
      hyperpolarized 129Xe in the dissolved phase in vivo is valuable to the
      development of clinical applications. The goal of this study was to develop a
      stable hyperpolarized 129Xe experimental 3T system to statistically analyze the
      dissolved-phase 129Xe signal in the rat lungs. The polarization of 129Xe with
      buffer gases at the optical pumping cell was measured under adiabatic fast
      passage against the temperature of an oven and laser absorption at the cell. The
      gases were insufflated into the lungs of Sprague-Dawley rats (n = 15, 400-550 g)
      through an endotracheal tube under spontaneous respiration. Frequency-selective
      spectroscopy was performed for the gas phase and dissolved phase. We analyzed the
      129Xe signal in the dissolved phase to measure the chemical shift, T2*, delay and
      its ratio in a rat lungs on 3T. The polarizer was able to produce polarized gas
      (1.1+/-0.47%, 120 cm3) hundreds of times with the laser absorption ratio (25%)
      kept constant at the cell. The optimal buffer gas ratio of 25-50% rendered the
      maximum signal in the dissolved phase. Two dominant peaks of 211.8+/-0.9 and
      201.1+/-0.6 ppm were observed with a delay of 0.4+/-0.9 and 0.9+/-1.0 s from the
      gas phase spectra. The ratios of their average signal to that of the gas phase
      were 5.6+/-5.2% and 4.4+/-4.7%, respectively. The T2* of the air space in the
      lungs was 2.5+/-0.5 ms, which was 3.8 times shorter than that in a syringe. We
      developed a hyperpolarized 129Xe experimental system using a 3T MRI scanner that
      yields sufficient volume and polarization and quantitatively analyzed the
      dissolved-phase 129Xe signal in the rat lungs.

PMID- 16093615
TI  - The optimal trackability threshold of fractional anisotropy for diffusion tensor
      tractography of the corticospinal tract.
AB  - PURPOSE: In order to ensure that three-dimensional diffusion tensor tractography
      (3D-DTT) of the corticospinal tract (CST), is performed accurately and
      efficiently, we set out to find the optimal lower threshold of fractional
      anisotropy (FA) below which tract elongation is terminated (trackability
      threshold). METHODS: Thirteen patients with acute or early subacute ischemic
      stroke causing motor deficits were enrolled in this study. We performed 3D-DTT of
      the CST with diffusion tensor MR (magnetic resonance) imaging. We segmented the
      CST and established a cross-section of the CST in a transaxial plane as a region
      of interest. Thus, we selectively measured the FA values of the right and left
      corticospinal tracts at the level of the cerebral peduncle, the posterior limb of
      the internal capsule, and the centrum semiovale. The FA values of the CST were
      also measured on the affected side at the level where the clinically relevant
      infarction was present in isotropic diffusion-weighted imaging. RESULTS: 3D-DTT
      allowed us to selectively measure the FA values of the CST. Among the 267 regions
      of interest we measured, the minimum FA value was 0.22. The FA values of the CST
      were smaller and more variable in the centrum semiovale than in the other
      regions. The mean minus twice the standard deviation of the FA values of the CST
      in the centrum semiovale was calculated at 0.22 on the normal unaffected side and
      0.16 on the affected side. CONCLUSION: An FA value of about 0.20 was found to be
      the optimal trackability threshold.

PMID- 16093616
TI  - Assessment of myocardial creatine concentration in dysfunctional human heart by
      proton magnetic resonance spectroscopy.
AB  - Creatine depletion in the non-viable infarcted human heart was previously
      demonstrated with proton magnetic resonance (MR) spectroscopy (1H MRS). In the
      present study, we assessed total creatine (CR) in human hearts with non-ischemic
      dysfunctions such as cardiomyopathy. Using cardiac-gated 1H MRS with MR image
      guided PRESS localization, we measured septal CR in healthy and diseased human
      hearts. Fifteen patients with chronic heart failure (CHF, left ventricular
      ejection fraction < 45%) and 14 age-matched normal subjects were examined.
      Myocardial CR was significantly (p < 0.001) lower in failing hearts (15.1+/-SD
      5.0 micromol/g wet weight, range 8.0-22.9) than in normal hearts (27.6+/-4.1
      micromol/g wet weight, range 20.8-36.2). Myocardial CR concentrations in six
      heart failure patients with plasma B-type natriuretic peptide (BNP) levels of >
      200 pg/ml (11.5+/-0.9 micromol/g wet weight, range 9.9-12.3) were significantly
      lower than those in four heart failure patients with plasma BNP levels of < 200
      pg/ml (19.8+/-2.5 micromol/g wet weight, range 17.7-22.9, p < 0.001). Thus, our
      study showed that myocardial CR was decreased in non-ischemic dysfunctional
      hearts. Noninvasive measurements of myocardial CR by 1H MRS may be useful in the
      assessment of the severity of heart failure.

PMID- 16093617
TI  - Utilization of low-field MR scanners.
AB  - The evident advantage of high-field MR (magnetic resonance) scanners is their
      higher signal-to-noise ratio, which results in improved imaging. While no
      reliable efficacy studies exist that compare the diagnostic capabilities of low-
      versus high-field scanners, the adoption and acceptance of low-field MRI
      (magnetic resonance imaging) is subject to biases. On the other hand, the cost
      savings associated with low-field MRI hardware are obvious. The running costs of
      a non-superconductive low-field scanner show even greater differences in favor of
      low-field scanners. Patient anxiety and safety issues also reflect the advantages
      of low-field scanners. Recent technological developments in the realm of low
      field MR scanners will lead to higher image quality, shorter scan times, and
      refined imaging protocols. Interventional and intraoperative use also supports
      the installation of low-field MR scanners. Utilization of low-field systems has
      the potential to enhance overall cost reductions with little or no loss of
      diagnostic performance.

PMID- 16093618
TI  - Performance assessment of phased-array coil in breast MR imaging.
AB  - PURPOSE: To compare the performance of the phased-array coil (PAC) with that of
      the single-loop coil (SLC) in magnetic resonance (MR) imaging of the breast.
      MATERIALS AND METHODS: MR imaging was performed with a 1.5T MR imager. A phantom
      study was performed with the right element of the two coils to obtain their
      signal-to-noise ratio (SNR). MR images of the breasts of 12 patients with breast
      lesions were obtained with the PAC and SLC, and these images were reviewed by
      five readers in a blind evaluation employing a scoring system for assessing
      overall image quality. RESULTS: In the phantom study, the SLC exhibited a SNR
      1.82 times higher than that of the PAC at the center of the coil; however, the
      SLC exhibited an inhomogeneous sensitivity profile and its SNR varied with the
      distance from the center of the coil in the horizontal and vertical directions.
      In most of the 12 patients, the MR images obtained with the PAC showed more noise
      than did those obtained with the SLC, and the PAC obtained lower scores than the
      SLC in the assessment of overall image quality; however, the difference was
      significant (p < 0.05) only in coronal imaging. On the other hand, the uniformity
      of fat saturation in the MR images obtained with the PAC was judged to be
      significantly superior to that obtained with the SLC (p < 0.05). CONCLUSION:
      Compared with the SLC, the PAC exhibited a lower SNR and was less advantageous at
      depicting the breast. However, the PAC provided more homogeneous fat saturation
      and might be useful for reducing artifacts.

PMID- 16093619
TI  - Cardiac cine parallel imaging on a 0.7T open system.
AB  - BACKGROUND: Parallel imaging can be applied to cardiac imaging with a cylindrical
      MRI (magnetic resonance imaging) apparatus. Studies of open MRI, however, are
      few. This study sought to achieve cardiac cine parallel imaging (or RAPID, for
      "rapid acquisition through parallel imaging design") with an open 0.7T MRI
      apparatus. MATERIALS AND METHODS: Imaging time was shortened in all slice
      directions with the use of a dedicated four-channel RF receiving coil comprising
      solenoid coils and butterfly coils. Coil shape was designed through an RF-coil
      simulation that considered biological load. The auto-calibration of a 0.7T open
      MRI apparatus incorporated a modified image-domain reconstruction algorithm. Cine
      images were obtained with a BASG, or balanced SARGE (steady-state acquisition
      with rewound gradient echo), sequence. Image quality was evaluated with
      cylindrical phantoms and five healthy volunteers. RESULTS: Multi-slice phantom
      images showed no visible artifacts. Cine images taken under breath-hold with an
      acceleration factor of two were evaluated carefully. With auto-calibration, the
      images revealed no visible unfolded artifacts or motion artifacts. RAPID thus
      improved the acquisition speed, time resolution, and spatial resolution of short
      axis, long-axis, and four-chamber images. CONCLUSION: The use of a dedicated RF
      coil enabled cardiac cine RAPID to be performed with an open MRI apparatus.

PMID- 16093620
TI  - Brain chip: a hypothesis.
AB  - This article is the English version of the Brain Chip hypothesis previously
      presented in the books "Brain Equation One Plus One (Kinokuniya, 2001)" and "Plus
      Alpha (Kinokuniya, 2002)." The concept in this article has been translated into
      English by the author himself in response to an overwhelming number of requests
      from colleagues outside Japan.

PMID- 16093621
TI  - Optimization of Gd-DTPA-enhanced balanced turbo field echo sequence in abdominal
      imaging: a basic study.
AB  - PURPOSE: To determine the optimum imaging conditions for the balanced turbo field
      echo (bTFE) sequence in abdominal imaging, we performed phantom experiments and
      scanning of a normal volunteer while noting the correlation among signal
      intensity, k-space ordering, flow velocity and Gd-DTPA concentration. MATERIALS
      AND METHODS: Initially, the abdomen of a healthy volunteer and some samples
      (water, blood and bovine albumin solutions with various Gd-DTPA concentrations,
      and olive oil) were examined with the bTFE sequence under various conditions to
      define the correlation among signal intensity, k-space ordering and Gd-DTPA
      concentration. Another experiment was performed to assess the correlation between
      the flow velocity and Gd-DTPA concentration. With the centric-bTFE sequence, we
      measured the signal intensity of water samples having various Gd-DTPA
      concentrations flowing in a long tube with an internal diameter of 4 mm. RESULTS:
      The experiments revealed the following issues: (i) The contrast of bTFE images
      was much influenced by k-space ordering; (ii) Gd-DTPA did not exhibit an overt
      enhancement effect in water and blood under stable conditions; (iii) The signal
      intensity of moving water decreased in centric-bTFE images, and this signal drop
      became more significant as the fluid speed increased; and (iv) Gd-DTPA decreased
      the range of signal loss in the moving fluid; however, this effect had no
      correlation with Gd-DTPA concentration. CONCLUSION: When the bTFE sequence was
      employed for abdominal imaging, centric view ordering, fat suppression and Gd
      DTPA contrast enhancement were assumed to be necessary.

PMID- 16093622
TI  - Optimization of Gd-DTPA-enhanced balanced turbo field echo sequence in abdominal
      imaging: clinical application.
AB  - PURPOSE: We performed MRI examinations of patients in order to confirm the
      enhancement effect of the balanced turbo field echo (bTFE) sequence with centric
      view ordering and SPIR (SPIR-centric-bTFE) as mentioned in the prior paper, and
      to evaluate the actual image quality of this sequence. MATERIALS AND METHODS: The
      upper abdomens of 30 patients with various abdominal disorders were examined with
      the SPIR-centric-bTFE sequence before and after Gd-DTPA administration. To assess
      the enhancement effect of Gd-DTPA, ROI measurements were taken in the aorta,
      superior mesenteric artery, portal vein, liver and bile juice in the common bile
      duct in each patient both in pre- and postcontrast images. Visual evaluations
      were also carried out in order to depict the peripheral vessels in the peritoneal
      fat and the apparent brightness of the soft-tissue organs. RESULTS: In all
      patients, the signal of the arteries after Gd-DTPA administration increased by
      about 50% compared with precontrast images. On the other hand, the veins and the
      liver showed a signal gain of less than 20% in postcontrast images. Consequently,
      only the signal of the arteries appeared enhanced in the postcontrast images. The
      visual evaluation revealed that postcontrast SPIR-centric-bTFE acquisition can
      depict the thin vessels clearly and the abdominal soft-tissue organs brightly.
      CONCLUSION: The balanced turbo field echo sequence with centric view ordering and
      SPIR after Gd-DTPA injection was considered the most appropriate protocol when
      this sequence was employed for abdominal imaging.

PMID- 16093623
TI  - Diffusion-weighted imaging of breast cancer with the sensitivity encoding
      technique: analysis of the apparent diffusion coefficient value.
AB  - PURPOSE: The usefulness of diffusion-weighted imaging (DWI) in the field of
      neuroradiology has been established. Despite its high contrast resolution, DWI
      has the disadvantages of susceptibility artifact and chemical shift artifact. We
      performed DWI of breast cancer with the sensitivity encoding (SENSE) technique.
      METHODS: The subjects were 60 female patients with breast mass. All patients
      underwent MRI including SENSE-DWI and were diagnosed histologically. Of these
      patients, 55 were diagnosed with breast cancer and the remaining five were
      diagnosed with benign mass. The histological diagnoses of breast cancer were as
      follows: 39 cases of invasive ductal carcinoma (IDC); 11 cases of IDC with a
      predominant intraductal component and non IDC (pure or predominant NIDC); and
      five cases of special types of cancer. The MR system used was a Gyroscan Intera
      1.5T (Philips Medical Systems). In addition to routine MRI for breast cancer,
      including contrast-enhanced dynamic, SENSE-DWI was obtained. The accuracy of the
      positional information of SENSE-DWI was visually compared with that of
      conventional images. The apparent diffusion coefficient (ADC) values of breast
      mass were analyzed with SENSE-DWI. RESULTS: The accuracy of positional
      information was adequate for diagnosing of all patients. The mean ADC value of
      breast cancer was 1.021x10(-3) mm2/s and that of benign mass was 1.488x10(-3)
      mm2/s (p=0.0002). The mean ADC value of IDC was 0.968x10(-3) mm2/s and that of
      pure or predominant NIDC was 1.218x10(-3) mm2/s (p=0.0011). CONCLUSION: SENSE-DWI
      was of sufficient quality to support diagnosis of breast mass. SENSE-DWI may
      permit the acquisition of more detailed information about lesions, including
      tumor cellularity, that is difficult to obtain with conventional techniques.

PMID- 16093624
TI  - Detection of hepatocellular carcinoma using double-echo FLASH sequence during the
      hepatic arterial phase.
AB  - PURPOSE: The purpose of this study was to compare the performance of in-phase and
      opposed-phase gradient-recalled echo (GRE) pulse sequences in paramagnetic
      contrast-enhanced magnetic resonance (MR) imaging of hepatocellular carcinomas
      (HCCs) during the hepatic arterial phase. MATERIAL AND METHODS: Thirty-four
      patients with 84 lesions with known or suspected HCCs, nine of whom had a fatty
      liver, were examined with double-echo GRE techniques under 1.5T before and 30 s
      after injection of gadopentenate dimeglumine at a dose of 0.1 mmol/kg. Echo times
      were 2.4 ms (opposed phase) and 5.0 ms (in phase). Contrast enhancement of the
      HCC detected in both in-phase and opposed-phase images was evaluated. The liver
      signal-to-noise ratio (SNR), lesion-liver contrast-to-noise ratio (CNR), and
      enhancement ratio (ER) were calculated for the largest lesion of each patient.
      RESULTS: In dynamic gadolinium-enhanced images of the 84 HCCs, 81 (96.4%) were
      detected in both in-phase and opposed-phase images, two (2.4%) were detected in
      only in-phase images, and one (1.2%) was detected only in opposed-phase images.
      The liver SNR, CNR, and ER were 46.7+/-16.1, 15.2+/-10.3, and 0.637+/-0.268 for
      in-phase images, and 48.9+/-16.9, 16.3+/-11.8, and 0.647+/-0.309 for opposed
      phase images, respectively. In patients with a fatty liver, the SNR, CNR, and ER
      were 46.0+/-18.1, 21.7+/-17.9, and 0.525+/-0.231 for in-phase images, and 44.3+/
      18.7, 26.0+/-21.3, and 0.793+/-0.124 for opposed-phase images, respectively. No
      significant statistical differences were found between the in-phase and opposed
      phase images. CONCLUSION: Opposed-phase GRE imaging is equivalent to in-phase GRE
      sequences in patients with or without fatty liver for detection of HCC in dynamic
      gadolinium-enhanced images.

PMID- 16093625
TI  - Accuracy of MR temperature measurement based on chemical shift change for
      radiofrequency ablation using hook-shaped electrodes.
AB  - The purpose of the current study is to evaluate the accuracy of MR thermometry
      for radiofrequency ablation (RFA) with hook-shaped electrodes. The objects were
      eight extracted bovine livers. The chemical shift change was calculated from MR
      images acquired with a spoiled gradient echo sequence and compared with the
      temperature directly measured with a thermocouple. Linear regression was
      established between them with a coefficient of -0.0110+/-0.0007 ppm/ degrees C
      and errors were calculated as -0.50+/-7.50 degrees C. MR thermometry is capable
      of monitoring temperature for RFA.

PMID- 16093626
TI  - Multicystic acoustic schwannoma with intratumoral hemorrhage: a report of two
      cases.
AB  - We encountered two multicystic acoustic schwannomas with intratumoral hemorrhage.
      The radiological appearance in each case was similar to that obtained with CT and
      MRI. From a histological perspective, in each case we observed hypervascularity
      with thin-walled, dilated vessels in clusters and hemosiderin depositions around
      the dilated vessels.

PMID- 16093627
TI  - Automatic motion correction for quantification of myocardial perfusion with
      dynamic magnetic resonance imaging.
AB  - Respiratory motion makes it difficult to quantify myocardial perfusion with
      dynamic magnetic resonance imaging (MRI). The purpose of this study was to
      evaluate an automatic registration method for motion correction for
      quantification of myocardial perfusion with dynamic MRI. The present method was
      based on the gradient-based method with robust estimation of displacement
      parameters. For comparison, we also corrected for motion with manual registration
      as the benchmark. The myocardial kinetic parameters, K1 (rate constant for
      transfer of contrast agent from blood to myocardium) and k2 (rate constant for
      transfer from myocardium to blood), were calculated from dynamic images with a
      two-compartment model. The images corrected by the present method were similar to
      those corrected by manual registration. The kinetic parameters obtained after
      motion correction with the present method were close to those obtained after
      motion correction with manual registration. These results suggest that the
      present method is useful for motion correction for quantification of myocardial
      perfusion with dynamic MRI.

PMID- 16093628
TI  - Comparison of true FISP with turbo SE in ovarian imaging.
AB  - PURPOSE: To compare the signal pattern of True FISP (true fast imaging with
      steady state precession) with that of T2-weighted TSE (turbo spin echo)
      sequencing in several ovarian pathologies and to clarify the pathologies that may
      be misdiagnosed when True FISP is used as a fast T2-weighted MR (magnetic
      resonance) imaging technique. METHODS: A total of 56 patients with 58 ovarian
      lesions were prospectively studied. The histopathological diagnoses were
      surgically confirmed in all patients. All MR images were acquired with a 1.5T MR
      scanner. After routine MR examination (T2-weighted sagittal imaging with a turbo
      spin echo sequence and T1 and T2 transverse imaging with a spin echo and turbo
      spin echo sequence, respectively), True FISP was performed in the sagittal plane
      with a fat-saturation technique. The acquisition times for the True FISP and TSE
      techniques were 27 s and 4 min, 42 s, respectively. Three radiologists
      interpreted all images according to three grading scores and with particular
      reference to the difference in signal pattern between the two sequences
      (1=similar signal patterns in the ovarian lesions in both True FISP and TSE
      images; 2=partially different signal patterns in both True FISP and TSE images;
      and 3=conflicting signal patterns in both True FISP and TSE images). RESULTS:
      Those assigned a score of "1" included 30 patients with 30 ovarian lesions (12
      malignant lesions and 18 benign lesions); those assigned a score of "2" included
      10 patients with 10 lesions (two malignant and eight benign); and those assigned
      a score of "3" included 16 patients with 18 ovarian lesions (two malignant and 16
      benign). With the influence of the fat-suppression technique excluded, eight
      ovarian lesions showed conflicting signal patterns between the two sequences and
      high signal intensity of hemorrhaging in the corresponding lesion in T1-weighted
      images. Lesions of both high and low signal intensity in TSE images appeared as
      lesions of high signal intensity in True FISP images. About 14% (8/56 lesions) of
      the True FISP and TSE signal patterns in ovarian pathology were conflicting in
      this study. CONCLUSION: The results indicate that the True FISP technique cannot
      replace the T2-weighted TSE technique in the evaluation of ovarian pathology. T1
      weighted images with or without fat suppression are required for the evaluation
      of ovarian lesions with FISP images.

PMID- 16093629
TI  - Morning glory sign: a particular MR finding in progressive supranuclear palsy.
AB  - BACKGROUND AND PURPOSE: We have encountered a peculiar atrophic change in the
      midbrain in some patients with parkinsonian syndromes. We discovered these
      patients had vertical supranuclear gaze-palsy, an eye movement disorder. The
      purpose of this study was to elucidate whether this atrophic pattern of the
      midbrain (which we have termed morning glory sign) is related to the vertical eye
      movement disorder, in particular to progressive supranuclear palsy (PSP).
      METHODS: We reviewed T2-weighted axial images obtained from 42 patients with
      parkinsonian syndromes, including five patients with PSP, 23 patients with
      Parkinson's disease, and 14 patients with multiple system atrophy (MSA). We
      focused on a specific atrophy of the midbrain, the morning glory sign, which is a
      concavity of the lateral margin of the tegmentum of the midbrain. RESULTS: The
      morning glory sign was detected in four of the five patients with PSP and in one
      (striatonigral degeneration; SND) of the14 patients with MSA. All morning glory
      sign patients had vertical supranuclear gaze-palsy, as did the one PSP patient
      without the morning glory sign. Vertical supranuclear gaze-palsy was seen in no
      other patients (23 patients with Parkinson's disease and 13 patients with MSA)
      who lacked the morning glory sign. CONCLUSIONS: Morphologically, the morning
      glory sign is believed to be related to vertical supranuclear gaze-palsy. This
      sign should be considered a useful clue when diagnosing PSP.

PMID- 16093630
TI  - Symmetrical lesions of the middle cerebellar peduncle: MR imaging and
      differential diagnosis.
AB  - The purpose of this paper is to show several diseases that manifest symmetrical
      hyperintense lesions on the middle cerebellar peduncles, the largest connecting
      peduncles between the brainstem and the cerebellum, in conventional magnetic
      resonance (MR) images. We retrospectively reviewed cranial MR images obtained
      with 0.3-, 0.5-, 1.0-, and 1.5-Tesla scanners. We found symmetrical middle
      cerebellar peduncular lesions in patients with Wilson's disease; hepatic
      encephalopathy; extrapontine myelinolysis; acute disseminated encephalomyelitis;
      wallerian degeneration of the pontocerebellar tracts after either pontine
      infarction, pontine hemorrhage, or central pontine myelinolysis; leukodystrophy;
      olivopontocerebellar atrophy; and toluene abuse. Definitive diagnosis of these
      diseases can be made relatively easily on the basis of clinical data; however,
      examination of associated brainstem or supratentorial lesions in MR images is
      also important.

PMID- 16093631
TI  - A case of probable hydroxyapatite deposition disease (HADD) of the hip.
AB  - We describe a patient with acute calcific periarthritis in an unusual site, the
      ilio-femoral ligament. The clinical findings in this patient resembled those of
      septic arthritis. T2*-weighted images with gradient field echo clearly showed
      foci of low signal intensity in this region, corresponding to the calcification
      shown on plain radiographs, and increased signal intensity around the foci,
      representing edema. These signal intensities were diagnostic of the disease.

PMID- 16093632
TI  - Computed tomography and magnetic resonance imaging of the pericardium: anatomy
      and pathology.
AB  - The purpose of this article is to review the characteristics of computed
      tomography (CT) and magnetic resonance imaging (MRI) of the pericardium and
      pericardial diseases. Because patients with pericardial diseases usually present
      with nonspecific symptoms, these diseases may not be detected until they have
      reached an advanced stage. It is therefore important to distinguish between
      normal pericardial structure and disease. Multiplanar reconstruction images of CT
      and MRI are useful for evaluating faint changes of the pericardium. The specific
      pericardial diseases described in this article include pericardial cyst,
      constrictive pericarditis, pericarditis with radiation pericarditis,
      postoperative pericardial hematoma, and cardiac tamponade due to a paracardiac
      mass (lymphoma).

PMID- 16093633
TI  - Dependence of the spin-spin relaxation time of water in collagen gels on collagen
      fiber directions.
AB  - In this study, we investigated the effect of structural differences in collagen
      fibers in relation to the spin-spin (T2) relaxation time of surrounding water
      molecules. We propose a simple experimental model of the magic angle effect based
      on magnetically oriented collagen gels. Experiments were performed with a 4.7T
      magnetic resonance imaging (MRI) system with a quadrature radio frequency coil
      operated at 200 MHz for 1H resonance. Collagen gels were polymerized from
      collagen solutions exposed to a 4.7T magnetic field for 120 min. The T2
      relaxation time was measured with the Carr-Purcell-Meiboom-Gill (CPMG) sequence.
      The apparent diffusion coefficient (ADC) was measured with the stimulated echo
      acquisition mode (STEAM) sequence with a motion-probing gradient (MPG). Orienting
      the collagen fibers at an angle of about 55 degrees to the main magnetic field
      caused an increase in the T2 relaxation times of water molecules in the collagen
      gels. The ADC in the direction parallel to the fibers was larger than that in the
      direction perpendicular to the fibers. The increase in the T2 relaxation time and
      ADC are attributed to a change in the magnetic interaction between the water
      molecules and collagen fibers.

PMID- 16093634
TI  - Detection of weak magnetic fields induced by electrical currents with MRI:
      theoretical and practical limits of sensitivity.
AB  - Detection of weak magnetic fields induced by neuronal electrical activities with
      magnetic resonance imaging (MRI) is a potentially effective method for functional
      imaging of the brain. In this study, we compared the theoretical and practical
      limits of sensitivity for detecting weak magnetic fields with a columnar phantom.
      The theoretical limit of sensitivity was estimated from signal and noise
      intensities in magnetic resonance images. The theoretical limit of sensitivity
      was approximately 10(-8)T. The practical limit was 10 times the theoretical
      limit. The dependence of the theoretical limit of sensitivity on acquisition
      parameters, such as the repetition time (TR), echo time (TE), number of pixels,
      and spectral width, was quantitatively evaluated. The results indicated the
      existence of an optimal value in T(E)/T2*.

PMID- 16093635
TI  - Deconvolution analysis of dynamic contrast-enhanced data based on singular value
      decomposition optimized by generalized cross validation.
AB  - PURPOSE: To present an implementation of generalized cross validation (GCV) for
      automatically determining the regularization parameter--i.e., the threshold value
      in deconvolution analysis based on truncated singular value decomposition (TSVD)
      of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data--and to
      investigate the usefulness of this approach in comparison with TSVD with a fixed
      threshold value (TSVD-F). METHODS: Using computer simulations, we generated a
      time-dependent concentration of the contrast agent in the volume of interest
      (VOI) from the arterial input function (AIF) modeled as a gamma-variate function
      under various cerebral blood flows (CBFs), cerebral blood volumes (CBVs), and
      signal-to-noise ratios (SNRs) for three different types of residue functions
      (exponential, triangular, and box-shaped). We also considered the effects of
      delay and dispersion in AIF. The TSVD with GCV (TSVD-G) and TSVD-F with a fixed
      threshold value of 0.2 were used to estimate CBF values from the simulated
      concentration-time curves in the VOI and AIF, and the estimated values were
      compared with the assumed values. Additionally, the optimal threshold value was
      determined from the threshold value in TSVD-F giving the mean CBF value closest
      to the assumed value and was compared with the threshold value determined with
      TSVD-G. RESULTS: With TSVD-G, the CBF estimation was substantially improved over
      a wide range of CBFs for all types of residue functions at the cost of more noise
      than was seen with TSVD-F. The dependency of the threshold value determined with
      TSVD-G on the CBF, CBV, and SNR was similar to that of the optimal threshold
      value, with some discrepancy being observed for the box-shaped residue function,
      although they did not always agree in terms of absolute value. CONCLUSION: Given
      an improved SNR, TSVD-G is useful for quantification of CBF with deconvolution
      analysis of DCE-MRI data.

PMID- 16093636
TI  - High-speed imaging at 3 Tesla: a technical and clinical review with an emphasis
      on whole-brain 3D imaging.
AB  - Improvements to the inherently high specific-absorption rate (SAR) of high-speed
      imaging at 3T are necessary in order to render this method clinically feasible.
      Various efforts have been undertaken to improve the associated hardware and
      software. In this review, we focus on whole-brain isotropic 3D imaging with a
      turbo spin-echo sequence with variable flip-angle echo trains (3D-TSE-VFL) and
      present its technical and clinical features. This sequence can be used to acquire
      images of various contrasts including T2-weighted, fat-suppressed T2-weighted,
      fluid-attenuated inversion recovery (FLAIR), fat-suppressed FLAIR, and STIR
      (short tau inversion recovery). Various aspects of 3D-TSE-VFL are discussed,
      including CSF (cerebrospinal fluid) and metal artifacts, STIR contrast, small
      part visualization other than brain, and the possibility of serial subtraction.
      Some images from clinical cases are presented.

PMID- 16093637
TI  - Interpretation of breast MRI: correlation of kinetic and morphological parameters
      with pathological findings.
AB  - Breast MRI (magnetic resonance imaging) has emerged as a highly sensitive
      modality for imaging of breast tumors. Differences in MR enhancement
      characteristics between benign and malignant lesions are believed to reflect
      differences in vascularity, vessel permeability, and extracellular diffusion
      space. However, interpretation of breast MRI remains a challenging task. Precise
      MR-pathologic correlations may also lead to an improved understanding of the
      histological heterogeneity of breast cancers and definitions of diagnostic
      criteria.

PMID- 16093638
TI  - Improvement of T1 determination of hyperpolarized 129Xe in mouse brain under
      controlled-flow.
AB  - The method of determining the longitudinal relaxation time of hyperpolarized
      129Xe in the mouse brain has been established in vivo with the ventilation
      technique under controlled-flow conditions. The uptake and washout processes for
      nine mice were traced through observation of time-dependent changes in NMR
      (nuclear magnetic resonance) signal amplitudes and analyzed by means of a two
      compartment model, thus providing the quantitative value of 14.1+/-1.6 s as the
      relaxation time.

PMID- 16093639
TI  - Averaging keyhole pulse sequence with presaturation pulses and EXORCYCLE phase
      cycling for dynamic contrast-enhanced MRI.
AB  - The purpose of this study was to design a keyhole pulse sequence for quantitative
      2D dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on a
      spoiled gradient echo T1-weighted acquisition. Saturation recovery was applied to
      achieve a linear correlation between signal intensity and contrast agent
      concentration in an arterial input function (AIF) while simultaneously removing
      time-of-flight effect. To remove ghosting artifacts arising from incomplete
      presaturation, EXORCYCLE phase cycling with averaging was applied to the pulse
      sequence. RF spoiling by radiofrequency switching with the synthesizer can be
      combined with EXORCYCLE phase cycling. Images affected by the large difference in
      signal intensity before and after contrast agent administration with the keyhole
      technique were improved by interleaving of peripheral lines of k-space with
      groups of central lines. Both peripheral and central lines were renewed during
      the dynamic scan. AIFs were obtained from the rat abdominal aorta with this
      keyhole sequence.

PMID- 16093640
TI  - Reversible focal splenial lesion of the corpus callosum on MR images in a patient
      with malnutrition.
AB  - T2-weighted MR (magnetic resonance) images of a 19-year-old woman undergoing
      concurrent chemoradiotherapy for a nasopharyngeal carcinoma revealed a lesion
      marked by focal hyper signal intensity in the splenium of the corpus callosum.
      The lesion was not visible two weeks later. She suffered from malnutrition caused
      by appetite loss during chemotherapy. We concluded that the lesion revealed by
      the abnormal signal intensity in the splenium had been caused by malnutrition.

PMID- 16093641
TI  - Morning glory sign is not prevalent in progressive supranuclear palsy.

PMID- 16093643
TI  - Emetic responses and neural activity in young musk shrews during the breast
      feeding/weaning period: comparison between the high and low emetic response
      strains using a shaking stimulus.
AB  - The high emetic response (HER) strain and low emetic response (LER) strain of
      musk shrews (Suncus murinus) markedly differ in the emetic reflex in adults.
      However, there have been no studies on young musk shrews. We gave a shaking
      stimulus to young musk shrews aged 10 days or more that were obtained by mating
      within each strain and observed emetic responses. In the HER strain, no animal
      aged 10 days vomited, but vomiting was observed in 1 of 5 animals each aged 12
      and 14 days, 2 of 5 animals aged 16 days, and all animals aged 18 days or more.
      In the LER strain, no vomiting was observed until the age of 14 days, but at the
      age of 16 days or more, 1 or 2 of 5 animals at each age vomited. After
      stimulation, activated neurons of the dorsal vagal complex and the dorsal
      reticular formation of the nucleus ambiguus (Amb) were examined by Fos
      immunohistochemistry. This morphometric study demonstrated that the numbers of
      Fos-positive neurons in the nucleus of the solitary tract and the dorsal
      reticular formation of the Amb were significantly larger in the animals that
      vomited in the HER strain than animals that did not vomit in the LER strain. We
      suggest that neurons in these regions are involved in emetic responses, as is the
      case in adult animals.

PMID- 16093644
TI  - Effects of nitric oxide synthase inhibitor on the digestive system measured by
      simultaneous monitoring of gastric motility, gastric emptying activity and
      postprandial pancreaticobiliary secretion in dogs.
AB  - Relationships between the NO synthase inhibitor and gastric and
      pancreaticobiliary functions measured simultaneously in the digestive state have
      been little studied. The aim of this study was to estimate the effect of NO
      synthase inhibitor on integrated digestive function in conscious dogs. A strain
      gauge force transducer was implanted on the gastric antrum of 6 mongrel dogs to
      measure gastric contractile activity and two duodenal cannulas were inserted into
      the proximal and distal sites to measure the gastric emptying rate and the
      pancreaticobiliary output into the duodenum using our novel method. Postprandial
      pancreatic and biliary secretion were presented as amylase and bile acid
      activity, respectively. Furthermore, a cervical cannula was placed into the
      superior vena cava as a route for the administration of NO synthase inhibitor, N
      omega-nitro-L-arginine (L-NNA), at a dose of 2.5 mg/kg-h. In a group given L-NNA,
      gastric contractile activity after ingestion was significantly enhanced, but the
      emptying rates of gastric solids and liquids were significantly suppressed in
      comparison with the control. The mean 0-1 h amylase integrated output was
      significantly (P < 0.05) decreased in comparison with the control, and the mean
      bile acid integration of 0-1 h output was also significantly (P < 0.01)
      decreased. A possible explanation for this observation is that smaller volumes of
      nutrient are delivered into the duodenum; however, it could also be that
      postprandial pancreaticobiliary secretion is inhibited by an alteration of blood
      flow or by a change in contractions of the sphincter of Oddi after the
      administration of L-NNA.

PMID- 16093645
TI  - Quantitative trait Loci for glomerulosclerosis, kidney weight and body weight in
      the focal glomerulosclerosis mouse model.
AB  - In 183 male progeny derived from a backcross between the FGS/Kist strain, a new
      mouse model for focal glomerulosclerosis (FGS) in humans, and the standard normal
      strain, C57BL/6J, we performed a genome-wide scan for quantitative trait loci
      (QTLs) affecting the glomerulosclerosis index (GSI) based on histological
      observation as well as kidney and body weights. Two QTLs for GSI (Gsi1-2) located
      on chromosomes (Chrs) 8 and 10, a kidney weight QTL (Kdw1) on Chr 19, and a body
      weight QTL (Bdw1) on Chr 13 were detected at the genome-wide 5% or less level.
      The allele derived from FGS/Kist increased GSI at Gsi1, but decreased it at Gsi2.
      The mice homozygous for the FGS/Kist allele decreased body and kidney weights.
      The identified QTLs accounted for 5-8% of the phenotypic variance.

PMID- 16093646
TI  - Arrest of spermatogenesis at the early meiotic stage in the small testis mutant
      (Smt) mice.
AB  - A spontaneous mutant having small testes was found in a laboratory mouse strain
      of mixed origins. The testis size was 1/3-1/2 of normal size, but no significant
      difference was seen in body mass and weight of organs such as kidney and seminal
      vesicle, which are influenced by androgen. Small testis males were found to be
      infertile by the mating test, although formation of a vaginal plug was normally
      observed in their female partners. Histological and air-dried specimens revealed
      degeneration of zygotene or early pachytene spermatocytes and very few numbers of
      pachytene and diplotene spermatocytes, round and elongate spermatids and mature
      spermatozoa in the mutant testis. Therefore, it was concluded that
      spermatogenesis is disrupted at the zygotene to early pachytene stages of meiosis
      in the mutant males. Segregation ratios of normal and mutant males were in accord
      with the assumption that the small testis character is caused by an autosomal
      recessive mutation. This mutant may be useful for research that would contribute
      to the elucidation of genetic mechanisms controlling the process of
      spermatogenesis and as a model animal for male infertility in humans.

PMID- 16093647
TI  - A mutant mouse with severe anemia and skin abnormalities controlled by a new
      allele of the flaky skin (fsn) locus.
AB  - We found a novel recessive mutation in an inbred strain, INT, that was derived
      from an ICR closed colony. Mice homozygous for this mutation are identified by
      severe anemia, dysgenesis and neonatal death. This mutation was tentatively named
      int. Intercrosses of int heterozygotes (+/int) and the flaky skin heterozygotes
      (+/fsn) resulted in abnormal mice (int/fsn heterozygotes) showing anemia and
      flaky skin with the expected frequency for autosomal recessive mutation. The int
      gene was therefore named fsn(Jic) as an allele of the fsn locus on chromosome 17.
      We carried out phenotype analyses using B6.INT- fsn(Jic) mice to observe
      phenotypes of blood and skin in the embryonic and neonatal stages. Discrimination
      of fsn(Jic) embryos from normal embryos was performed by an indirect diagnosis of
      the fsn(Jic) gene using the D17Mit130 microsatellite marker tightly linked to the
      fsn locus. The number of fetal nucleated RBC of normal embryos decreased
      gradually to 17.5 dpc, but that of the abnormal embryos decreased to 14.5 dpc
      followed by a gradual increase to 17.5 dpc. Skin of fsn(Jic) embryos did not show
      any abnormalities and expressed cytokeratins normally as skin epithelial cell
      markers at each embryonic stage (15.5 dpc to 18.5 dpc). Time differences in the
      appearance of the different phenotypes observed in various tissue and organs of
      fsn homozygotes suggest they are caused by expression of the fsn gene at
      different developmental stages.

PMID- 16093648
TI  - Different pattern of pinopodes expression in stimulated mouse endometrium.
AB  - Adult NMRI mice were superovulated using human menopausal chorionic gonadotropic
      hormones (hMG and hCG), and then some of them were daily injected with
      progesterone (1 mg/mouse). At 3.5 and 4.5 days after hCG injection scanning
      electron micrographs revealed that the hyperstimulated and progesterone-injected
      group had well-developed pinopodes while most of the hyperstimulated group
      without progesterone injection had no pinopodes 3.5 days after stimulation. The
      results suggest that the lifespan of pinopodes is short and changeable during
      hyperstimulation and that progesterone causes premature formation of the
      pinopodes and that implantation after ovarian stimulation might depend upon the
      timing of the pinopode expression.

PMID- 16093649
TI  - Establishment of a SPF colony of human apo(a) transgenic rabbits by frozen-thawed
      embryo transfer.
AB  - In the present study, embryo transfer was performed using frozen-thawed embryos
      to establish a SPF colony of human apolipoprotein (a) (apo(a)) transgenic
      rabbits. Apo(a) transgenic rabbits were kept under conventional condition and
      were infected with Bordetella bronchiseptica. Embryos at the morula stage were
      collected and stored in liquid nitrogen. After thawing, the in vitro survival
      rate was 84.6%, and 125 morphologically normal embryos were transferred to 6 SPF
      recipient rabbits. Four rabbits became pregnant and 23 live pups were born. PCR
      and Western blot analyses revealed that 9 of 23 pups were transgenic and
      expressed apo(a) protein. Microbiological tests showed all rabbits were free from
      infections. We succeeded in establishing a SPF colony of apo(a) transgenic
      rabbits. These rabbits are now maintained under a barrier system and are
      available for medical research.

PMID- 16093650
TI  - Differential identification of mycoplasma pulmonis and M. arthritidis using PCR
      based RFLP.
AB  - Mycoplasma pulmonis and Mycoplasma arthritidis were differentially identified
      using PCR-restriction fragment length polymorphism (RFLP). A genus-specific
      sequence of mycoplasma was amplified by PCR and the PCR products were digested
      with the restriction enzyme SmaI. Each PCR product from the four isolates of M.
      pulmonis was digested with SmaI into two fragments; however, there was no
      digestion in the PCR product from M. arthritidis. This method might be useful to
      differentiate infection of M. pulmonis from that of M. arthritidis.

PMID- 16093651
TI  - Histopathological studies of aortic dissection in streptozotocin-induced diabetic
      APA hamsters.
AB  - Syrian hamsters of the APA strain (APA hamsters) are known to show continuous
      diabetes accompanied by its complications, such as glomerulosclerosis and
      atherosclerosis, following a single injection of streptozotocin (SZ). Recently,
      we observed Stanford type B aortic dissection in three diabetic APA hamsters and
      histopathological analysis was performed. The histopathologic observations in the
      false lumen, such as proliferation of granulation tissues, neointima and
      pseudoneointima, corresponded to the non-thrombosed type of human aortic
      dissection, and blood clots of the thrombosed type were similar to the remodeling
      structures of aortic dissection found in human cases. Thus, this model may be
      useful for investigating the etiology and pathogenesis of aortic dissection
      accompanying diabetes mellitus in humans.

PMID- 16093652
TI  - Exposure to common anesthetic agents alters pup-retrieval response in lactating
      rats.
AB  - This study investigated the lactating stage of rats to determine the effect on
      maternal behavior of a single exposure to general anesthetic. Lactating Wistar
      rats were treated with anesthetic doses of pentobarbital (PENT) or ketamine (KET)
      on day 3 or 9 of lactation, and their behavioral responses were evaluated during
      a 50-min nursing period, after a 4-h mother-pup separation, on day 12. Exposure
      to KET on day 9 led to a significantly longer latency to pup-retrieval than that
      of the control. Duration of pup-retrieval in mothers treated with KET on day 3
      and 9 was significantly longer than in the control. Other components of maternal
      behavior did not differ between the groups. The present findings suggested that
      general anesthetics have an impact upon pup-retrieval activities, which
      indirectly represent maternal motivation.

PMID- 16093653
TI  - Microsatellite genotyping for genetic quality testing using sperm cells in the
      mouse.
AB  - We attempted to determine the number of sperm cells required for genotyping of
      one microsatellite marker. The crude genomic DNA extracted from about 760 or more
      sperm cells gave sufficient quantity of PCR product using a 20 microl-scale PCR.
      We also studied the effects of non-ionic detergents on extraction of crude sperm
      genomic DNA. PCR products amplified with the crude sperm genomic DNA extracted
      using the lysis buffer supplemented with non-ionic detergents showed much clear
      bands. In conclusion, our results suggest that a small part of the frozen sperm,
      which is less than 1/10 of the original volume (10 microl), provides sufficient
      quantity of template DNA for genetic quality testing.

PMID- 16093654
TI  - Echoes from the past--are we still in an RNP world?
AB  - Availability of the human genome sequence and those of other species is
      unmeasured in their value for a comprehensive understanding of the architecture,
      function and evolution of genomes and cells. Various mechanisms keep genomes in
      flux and generate intra- and interspecies variation. The conversion of RNA
      modules into DNA and their more or less random integration into chromosomes
      (retroposition) is in many lineages including our own the most pervasive and
      perhaps the most enigmatic. The proclivity of such events in extant multicellular
      eukaryotes, even in more recent evolutionary times, gives the impression that the
      transition period from the RNP (ribonucleoprotein) world to the emergence of
      modern cells, where DNA became the predominant carrier of genetic information,
      has lasted billions of years and is an endlessly drawn-out process rather than
      the punctuated event one might expect. Apart from the impact of such RNA-mediated
      processes as retroposition, the role of RNA in a wide variety of cellular
      functions has only recently become more widely appreciated.

PMID- 16093655
TI  - What transposable elements tell us about genome organization and evolution: the
      case of Drosophila.
AB  - Transposable elements (TEs) have been identified in every organism in which they
      have been looked for. The sequencing of large genomes, such as the human genome
      and those of Drosophila, Arabidopsis, Caenorhabditis, has also shown that they
      are a major constituent of these genomes, accounting for 15% of the genome of
      Drosophila, 45% of the human genome, and more than 70% in some plants and
      amphibians. Compared with the 1% of genomic DNA dedicated to protein-coding
      sequences in the human genome, this has prompted various researchers to suggest
      that the TEs and the other repetitive sequences that constitute the so-called
      "noncoding DNA", are where the most stimulating discoveries will be made in the
      future (Bromham, 2002). We are therefore getting further and further from the
      original idea that this DNA was simply "junk DNA", that owed its presence in the
      genome entirely to its capacity for selfish transposition. Our understanding of
      the structures of TEs, their distribution along the genomes, their sequence and
      insertion polymorphisms within genomes, and within and between populations and
      species, their impact on genes and on the regulatory mechanisms of genetic
      expression, their effects on exon shuffling and other phenomena that reshape the
      genome, and their impact on genome size has increased dramatically in recent
      years. This leads to a more general picture of the impact of TEs on genomes,
      though many copies are still mainly selfish or junk DNA. In this review we focus
      mainly on discoveries made in Drosophila, but we also use information about other
      genomes when this helps to elucidate the general processes involved in the
      organization, plasticity, and evolution of genomes.

PMID- 16093656
TI  - LINEs, SINEs and processed pseudogenes: parasitic strategies for genome modeling.
AB  - Two major classes of retrotransposons have invaded eukaryotic genomes: the LTR
      retrotransposons closely resembling the proviral integrated form of infectious
      retroviruses, and the non-LTR retrotransposons including the widespread,
      autonomous LINE elements. Here, we review the modeling effects of the latter
      class of elements, which are the most active in humans, and whose enzymatic
      machinery is subverted to generate a large series of "secondary" retroelements.
      These include the processed pseudogenes, naturally present in all eukaryotic
      genomes possessing non-LTR retroelements, and the very successful SINE elements
      such as the human Alu sequences which have evolved refined parasitic strategies
      to efficiently bypass the original "protectionist" cis-preference of LINEs for
      their own retrotransposition.

PMID- 16093657
TI  - Hybrid genome evolution by transposition.
AB  - Species hybridization is reviewed focusing on its role as a source of
      evolutionary novelties. Contrary to the view that hybrids are lineages devoid of
      evolutionary value, a number of case studies are given that show how hybrids are
      responsible for reticulate evolution that may lead to the origin of new species.
      Hybrid evolution is mediated by extensive genome repatterning followed by rapid
      stabilization and fixation of highly adapted genotypes. Some well-documented
      cases demonstrate that bursts of transposition follow hybridization and may
      contribute to the genetic instability observed after hybridization. The mechanism
      that triggers transposition in hybrids is largely unknown, but coupling of hybrid
      transposition and demethylation has been observed in mammals and plants. A
      natural scenario is proposed in which marginal small hybrid populations undergo
      transposition mediated genome reorganizations accompanied by exogenous and
      endogenous selection that, in concert with drift, lead to rapid fixation of high
      fitness hybrid genotypes. These genotypes may represent parental introgressed
      species or be entirely new species.

PMID- 16093658
TI  - Reverse transcription in genome evolution.
AB  - As reverse transcription is predominantly performed by retrotransposable
      elements, the process is often entirely associated with the propagation of these
      elements. However, as a unique tool for transmitting information from the dynamic
      RNA to the more inert DNA, reverse transcription has been instrumental in shaping
      extant genomes. This review aims at presenting the diversity by which reverse
      transcription has influenced modern genomic structures.

PMID- 16093659
TI  - Genome evolution mediated by Ty elements in Saccharomyces.
AB  - How mobile genetic elements molded eukaryotic genomes is a key evolutionary
      question that gained wider popularity when mobile DNA sequences were shown to
      comprise about half of the human genome. Although Saccharomyces cerevisiae does
      not suffer such "genome obesity", five families of LTR-retrotransposons, Ty1,
      Ty2, Ty3, Ty4, and Ty5 elements, comprise about 3% of its genome. The
      availability of complete genome sequences from several Saccharomyces species,
      including members of the closely related sensu stricto group, present new
      opportunities for analyzing molecular mechanisms for chromosome evolution,
      speciation, and reproductive isolation. In this review I present key experiments
      from both the pre- and current genomic sequencing eras suggesting how Ty elements
      mediate genome evolution.

PMID- 16093660
TI  - Happy together: the life and times of Ty retrotransposons and their hosts.
AB  - The aim of this review is to describe the level of intimacy between Ty
      retrotransposons (Ty1-Ty5) and their host the yeast Saccharomyces cerevisiae. The
      effects of Ty location in the genome and of host proteins on the expression and
      mobility of Ty elements are highlighted. After a brief overview of Ty diversity
      and evolution, we describe the factors that dictate Ty target-site preference and
      the impact of targeting on Ty and adjacent gene expression. Studies on Ty3 and
      Ty5 have been especially informative in unraveling the role of host factors (Pol
      III machinery and silencing proteins, respectively) and integrase in controlling
      the specificity of integration. In contrast, not much is known regarding Ty1, Ty2
      and Ty4, except that their insertion depends on the transcriptional competence of
      the adjacent Pol III gene and might be influenced by some chromatin components.
      This review also brings together recent findings on the regulation of Ty1
      retrotransposition. A large number of host proteins (over 30) involved in a wide
      range of cellular processes controls either directly or indirectly Ty1 mobility,
      primarily at post-transcriptional steps. We focus on several genes for which more
      detailed analyses have permitted the elaboration of regulatory models. In
      addition, this review describes new data revealing that repression of Ty1
      mobility also involves two forms of copy number control that act at both the
      trancriptional and post-transcriptional levels. Since S. cerevisiae lacks the
      conserved pathways for copy number control via transcriptional and post
      transcriptional gene silencing found in other eukaryotes, Ty1 copy number control
      must be via another mechanism whose features are outlined. Ty1 response to stress
      also implicates activation at both transcriptional and postranscriptional steps
      of Ty1. Finally, we provide several insights in the role of Ty elements in
      chromosome evolution and yeast adaptation and discuss the factors that might
      limit Ty ectopic recombination.

PMID- 16093661
TI  - LTR retrotransposons and flowering plant genome size: emergence of the
      increase/decrease model.
AB  - Long Terminal Repeat (LTR) retrotransposons are ubiquitous components of plant
      genomes. Because of their copy-and-paste mode of transposition, these elements
      tend to increase their copy number while they are active. In addition, it is now
      well established that the differences in genome size observed in the plant
      kingdom are accompanied by variations in LTR retrotransposon content, suggesting
      that LTR retrotransposons might be important players in the evolution of plant
      genome size, along with polyploidy. The recent availability of large genomic
      sequences for many crop species has made it possible to examine in detail how LTR
      retrotransposons actually drive genomic changes in plants. In the present paper,
      we provide a review of the recent publications that have contributed to the
      knowledge of plant LTR retrotransposons, as structural components of the genomes,
      as well as from an evolutionary genomic perspective. These studies have shown
      that plant genomes undergo genome size increases through bursts of
      retrotransposition, while there is a counteracting process that tends to
      eliminate the transposed copies from the genomes. This process involves
      recombination mechanisms that occur either between the LTRs of the elements,
      leading to the formation of solo-LTRs, or between direct repeats anywhere in the
      sequence of the element, leading to internal deletions. All these studies have
      led to the emergence of a new model for plant genome evolution that takes into
      account both genome size increases (through retrotransposition) and decreases
      (through solo-LTR and deletion formation). In the conclusion, we discuss this new
      model and present the future prospects in the study of plant genome evolution in
      relation to the activity of transposable elements.

PMID- 16093662
TI  - How repeated retroelements format genome function.
AB  - Genomes operate as sophisticated information storage systems. Generic repeated
      signals in the DNA format expression of coding sequence files and organize
      additional functions essential for genome replication and accurate transmission
      to progeny cells. Retroelements comprise a major fraction of many genomes and
      contain a surprising diversity of functional signals. In this article, we
      summarize some features of the taxonomic distribution of retroelements,
      especially mammalian SINEs, tabulate functional roles documented for different
      classes of retroelements, and discuss their potential roles as genome organizers.
      In particular, the fact that certain retroelements serve as boundaries for
      heterochromatin domains and provide a significant fraction of scaffolding/matrix
      attachment regions (S/MARs) suggests that the reversed transcribed component of
      the genome plays a major architectonic role in higher order physical structuring.
      Employing an information science model, the "functionalist" perspective on
      repetitive DNA leads to new ways of thinking about the systemic organization of
      cellular genomes and provides several novel possibilities involving retroelements
      in evolutionarily significant genome reorganization.

PMID- 16093663
TI  - Clustering, duplication and chromosomal distribution of mouse SINE
      retrotransposons.
AB  - We analyzed potential mechanisms determining chromosomal distributions of the
      mouse B1 and B2 non-LTR retrotransposons, also known as SINE elements. We report
      that young B1 and B2 SINEs are underrepresented on chromosome X relative to
      autosomes, which is consistent with their integration in male germ lines. As the
      age of the SINE elements progresses, their densities on chromosome X increase
      relative to autosomal densities, possibly due to differences in ectopic
      recombination rates between chromosome X and autosomes. Furthermore, unlike young
      human Alus that tend to be integrated outside Alu-dense regions, young B1 and B2
      elements are found mostly in SINE-rich clusters. The B1- or B2-rich clusters are
      more likely to contain duplicated elements than B1- or B2-poor chromosomal
      regions. We also present evidence indicating potential association of B1 and B2
      elements with intra-chromosomal segmental duplications. No such association was
      found with inter-chromosomal duplications. We propose that the accumulation of
      mouse SINE elements observed in GC-rich regions may be due to the excess of DNA
      duplications over deletions in gene-rich regions that tend to be GC rich.

PMID- 16093664
TI  - Heterochromatic distribution of HeT-A- and TART-like sequences in several
      Drosophila species.
AB  - Drosophila melanogaster telomeres contain arrays of two non-LTR retrotransposons
      called HeT-A and TART. Previous studies have shown that HeT-A- and TART-like
      sequences are also located at non-telomeric sites in the Y chromosome
      heterochromatin. By in situ hybridization experiments, we mapped TART sequences
      in the h16 region of the long arm close to the centromere of the Y chromosome of
      D. melanogaster. HeT-A sequences were localized in two different regions on the Y
      chromosome, one very close to the centromere in the short arm (h18-h19) and the
      other in the long arm (h13-h14). To assess a possible heterochromatic location of
      TART and HeT-A elements in other Drosophila species, we performed in situ
      hybridization experiments, using both TART and HeT-A probes, on mitotic and
      polytene chromosomes of D. simulans, D. sechellia, D. mauritiana, D. yakuba and
      D. teissieri. We found that TART and HeT-A probes hybridize at specific
      heterochromatic regions of the Y chromosome in all Drosophila species that we
      analyzed.

PMID- 16093665
TI  - Retroelements: tools for sex chromosome evolution.
AB  - Many eukaryotic taxa inherit a heteromorphic sex chromosome pair. It is a
      generally accepted hypothesis that the sex chromosome pair is derived from a pair
      of homologous autosomes that has developed after the occurrence of a sex
      differentiator in an evolutionary process into two structurally and functionally
      different partners. In most of the analyzed systems the occurrence of the
      dominant sex differentiator is paralleled by the suppression of recombination
      within and close by that region. The recombinational isolation can spread in an
      evolutionary selection process from neighboring regions finally over the whole
      chromosome. Suppression of recombination strongly biases the distribution of
      retrotransposons in the genome. Our results and that from others indicate that
      the major force driving the evolution of Y chromosomes are retrotransposons,
      remodeling euchromatic chromosome structures into heterochromatic ones. In our
      model, intact or already eroded retrotransposons become trapped due to their
      inherent transposition mechanisms in non-recombining regions. The massive
      accumulation of retrotransposons interferes strongly with the activity of genes.
      We hypothesize that Y chromosome degeneration is a stepwise evolutionary process:
      (1) Massive accumulation of retrotransposons occurs in the non-recombining
      regions. (2) Heterochromatic nucleation centers are formed as a consequence of
      genomic defense against invasive parasitic elements; the established nucleation
      centers become epigenetically inherited. (3) Spreading of heterochromatin from
      the nucleation centers into flanking regions induces in an adaptive process gene
      silencing of neighbored genes that could either be still intact or in an already
      eroded condition, e.g., showing point mutations, deletions, insertions; the
      retroelements should be subjects to the same forces of deterioration as the genes
      themselves. (4) Constitutive silenced genes are not committed to the same genetic
      selection pressure as active genes and therefore more exposed to the decay
      process. (5) Gene dosage balance is reestablished by the parallel evolution of
      dosage compensation mechanisms. The evolving secondary sex chromosomes, neo-X and
      neo-Y, of Drosophila miranda are revealed to be a unique and potent model system
      to catch the evolutionary Y deterioration process in progress.

PMID- 16093666
TI  - Retrotransposable elements on the W chromosome of the silkworm, Bombyx mori.
AB  - The sex chromosomes of the silkworm, Bombyxmori, are designated ZW(XY) for
      females and ZZ(XX) for males. The W chromosome of B. mori does not recombine with
      the Z chromosome and autosomes and no genes for morphological characters have
      been mapped to the W chromosome as yet. Furthermore, femaleness is determined by
      the presence of a single W chromosome, regardless of the number of autosomes or Z
      chromosomes. To understand these interesting features of the W chromosome, it is
      necessary to analyze the W chromosome at the molecular biology level. Initially
      to isolate DNA sequences specific for the W chromosome as randomly amplified
      polymorphic DNA (RAPD) markers, we compared the genomic DNAs between males and
      females by PCR with arbitrary 10-mer primers. To the present, we have identified
      12 W-specific RAPD markers, and with the exception of one RAPD marker, all of the
      deduced amino acid sequences of these W-specific RAPD markers show similarity to
      previously reported amino acid sequences of retrotransposable elements from
      various organisms. After constructing a genomic DNA lambda phage library of B.
      mori we obtained two lambda phage clones, one containing the W-Kabuki RAPD
      sequence and one containing the W-Samurai RAPD sequence and found that these DNA
      sequences comprised nested structures of many retrotransposable elements. To
      further analyze the W chromosome, we obtained 14 W-specific bacterial artificial
      chromosome (BAC) clones from three BAC libraries and subjected these clones to
      shotgun sequencing. The resulting assembly of sequences did not produce a single
      contiguous sequence due to the presence of many retrotransposable elements.
      Therefore, we coupled PCR with shotgun sequencing. Through these analyses, we
      found that many long terminal repeat (LTR) and non-LTR retrotransposons,
      retroposons, DNA transposons and their derivatives, have accumulated on the W
      chromosome as strata. These results strongly indicate that retrotransposable
      elements are the main structural component of the W chromosome.

PMID- 16093667
TI  - HeT-A and TART, two Drosophila retrotransposons with a bona fide role in
      chromosome structure for more than 60 million years.
AB  - Drosophila telomeres have been maintained by retrotransposition for at least 60
      MY, which predates the separation of extant species of this genus. Studies of D.
      melanogaster, D. yakuba, and D. virilis show that, in Drosophila, telomeres are
      composed of two non-LTR retrotransposons, HeT-A and TART. Far from being static,
      HeT-A and TART evolve faster than Drosophila euchromatic genes. In spite of their
      high rate of sequence change, HeT-A and TART maintain their basic structures and
      unusual individual features. The maintenance of their separate identities
      suggests that HeT-A and TART cooperate either in the process of
      retrotransposition onto the chromosome end, or in the formation of telomere
      chromatin by transposed DNA copies. The telomeric retrotransposons and the
      Drosophila genome constitute an example of a robust symbiotic relationship
      between mobile elements and the genome.

PMID- 16093668
TI  - I element distribution in mitotic heterochromatin of Drosophila melanogaster
      reactive strains: identification of a specific site which is correlated with the
      reactivity levels.
AB  - The I factor is a Drosophila melanogaster LINE-like element that efficiently
      transposes in the genetic system of I-R hybrid dysgenesis. It has been suggested
      that some of the I-related sequences located in the heterochromatin of D.
      melanogaster are involved in the regulation of I factor activity. In this work we
      have performed fluorescent in situ hybridization (FISH) mapping of I element
      sequences in mitotic heterochromatin of nine differentially reactive D.
      melanogaster strains. The results of our analysis showed that a single
      hybridization site mapping to region h28 of the distal heterochromatin of the X
      chromosome is present in three strains with low or intermediate levels of
      reactivity, while it is undetectable in six highly reactive strains. Together,
      these observations suggest a negative correlation between I sequences located at
      h28 and the level of reactivity. To this regard, it is intriguing that flamenco
      and COM, two loci that regulate the activity of D. melanogaster endogenous
      retroviruses also map to the distal heterochromatin of the X chromosome. Our data
      represent the first experimental evidence in favour of a silencing effect exerted
      by naturally occurring I element sequences located in pericentromeric
      heterochromatin.

PMID- 16093669
TI  - Transposable elements as artisans of the heterochromatic genome in Drosophila
      melanogaster.
AB  - Over 50 years ago Barbara McClintock discovered that maize contains mobile
      genetic elements, but her findings were at first considered nothing more than
      anomalies. Today it is widely recognized that transposable elements have
      colonized all eukaryotic genomes and represent a major force driving evolution of
      organisms. Our contribution to this special issue deals with the theme of
      transposable element-host genome interactions. We bring together published and
      unpublished work to provide a picture of the contribution of transposable
      elements to the evolution of the heterochromatic genome in Drosophila
      melanogaster. In particular, we discuss data on 1) colonization of constitutive
      heterochromatin by transposable elements, 2) instability of constitutive
      heterochromatin induced by the I factor, and 3) evolution of constitutive
      heterochromatin and heterochromatic genes driven by transposable elements.
      Drawing attention to these topics may have direct implications on important
      aspects of genome organization and gene expression.

PMID- 16093670
TI  - Fixed and unstable I-related transposable elements in heterochromatin of
      Drosophila melanogaster.
AB  - Transposable elements are disproportionately abundant in the heterochromatin of
      Drosophila melanogaster. Among the forces contributing to this bias in genomic
      distribution, fixation due to positive selection has been put forward. We have
      studied I-related elements which are located in pericentromeric heterochromatin
      and are believed to have a role in the control of active I elements. Flies
      straight from the wild have been studied where fixed elements are expected to
      emerge clearly over the highly polymorphic background in the genomic distribution
      of transposable elements. The results show that some restriction fragments due to
      I-related elements are conserved in size and are present in all individuals
      tested, consistent with a selective pressure for a role. Other fragments are
      polymorphic in presence/absence and intensity in individuals from the wild but
      appear homogeneous in laboratory stocks. Although the significance of this type
      of instability is unclear, the finding that these polymorphic bands are recurrent
      in populations from distant geographical locations is also suggestive of a
      selective pressure for a role.

PMID- 16093671
TI  - ERVK9, transposons and the evolution of MHC class I duplicons within the alpha
      block of the human and chimpanzee.
AB  - The genomic sequences within the alpha-block (approximately 288-310 kb) of the
      human and chimpanzee MHC class I region contains ten MHC class I genes and three
      MIC gene fragments grouped together within alternating duplicated genomic
      segments or duplicons. In this study, the chimpanzee and human genomic sequences
      were analyzed in order to determine whether the remnants of the ERVK9 and other
      retrotransposon sequences are useful genomic markers for reconstructing the
      evolutionary history of the duplicated MHC gene families within the alpha-block.
      A variety of genes, pseudogenes, autologous DNA transposons and retrotransposons
      such as Alu and ERVK9 were used to categorize the ten duplicons into four
      distinct structural groups. The phylogenetic relationship of the ten duplicons
      was examined by using the neighbour joining method to analyze transposon sequence
      topologies of selected Alu members, LTR16B and Charlie9. On the basis of these
      structural groups and the phylogeny of the duplicated transposon sequences, a
      duplication model was reconstructed involving four multipartite tandem
      duplication steps to explain the organization and evolution of the ten duplicons
      within the alpha-block of the chimpanzee and human. The phylogenetic analysis and
      inferred duplication history suggests that the Patr/HLA-F was the first MHC class
      I gene to have been fixed and not required as a precursor for further duplication
      within the alpha-block of the ancestral species.

PMID- 16093672
TI  - Polymorphic Alu insertions within the Major Histocompatibility Complex class I
      genomic region: a brief review.
AB  - Most polymorphic Alu insertions (POALINs) belong to a subgroup of the Alu
      multicopy retrotransposon family of short interspersed nucleotide elements
      (SINEs) that are categorized as AluYb8 and AluYa5. The number of AluYb8/AluYa5
      members (approximately 4,492 copies) is significantly less than the approximately
      one million fixed Alu copies per human genome. We have studied the presence of
      POALINs within the Major Histocompatibility Complex (MHC) class I region on the
      short arm of chromosome 6 (6p21.3) because this region has a high gene density,
      many genes with immune system functions, large sequence variations and diversity,
      duplications and redundancy, and a strong association with more than 100
      different diseases. Since little is known about POALINs within the MHC genomic
      region, we undertook to identify some of the members of the AluYb8/AluYa5
      subfamily and to study their frequency of distribution and genetic
      characteristics in different populations. As a result of our comparative genomic
      analyses, we identified the insertion sites for five POALINs distributed within
      the MHC class I region. This brief review outlines the locations of the
      insertions and sequence features of the five MHC POALINs, their single site and
      haplotype frequencies in different geographic populations, and their association
      with different HLA class I genes and disease. We show that the MHC POALINs have a
      potential value as lineage and linkage markers for the study of human population
      genetics, disease associations, genomic diversity and evolution.

PMID- 16093673
TI  - A comparative study of retrotransposons in the centromeric regions of A and B
      chromosomes of maize.
AB  - Bacterial Artificial Chromosomes (BACs) derived from the B chromosome, based on
      homology with the B specific sequence, were subcloned and sequenced. Analysis of
      DNA sequence data indicated the presence of 23 common retroelements, as well as
      novel sequences of B chromosome origin. Generally, where the same retrotransposon
      type was observed in both A and B chromosomes, there were more copies per unit of
      sequence in the B centromeric region (the major site of B repeat) than in the A
      centromere, except for Huck-1. Based on previous estimates of the age of the
      major burst of transposition into the maize genome, the oldest retrotransposons
      (Ji-6 and Tekay, approximately 5.0 and 5.2 million years ago, respectively) were
      found in the B centromere region only, while the next two oldest (Huck-1 and Opie
      1) were found in both the A and B sequences. Phylogenetic analysis of Opie
      retroelements from both A and B centromeres indicated that some of the B Opie
      centromeric sequences share a more recent common ancestor with A Opie
      retroelements than they do with other B Opie centromeric sequences. These results
      imply that the supernumerary maize B chromosome has coexisted with the A
      chromosomes during that period of transposition. They also support the hypothesis
      that the B chromosome had its origins from A chromosome elements, or that
      alternative origins, such as being donated to the maize genome in a wide species
      cross, preceded six million years ago, because the spectrum of retrotransposons
      in the two chromosomes is quite similar.

PMID- 16093674
TI  - Transcriptional interference mediated by retrotransposons within the genome of
      their host: lessons from alleles of the white gene from Drosophila melanogaster.
AB  - Systematic sequencing of model genomes has accelerated our knowledge on genome
      structure and shown that a large proportion of intergenic regions are made up of
      mobile element families. Among them, retrotransposons that are mobilized via an
      RNA intermediate and thus do not excise during their replication cycle are
      certainly essential factors able to imprint novel and heritable transcriptional
      regulation within the genome of their host. Today, a crucial complement to the
      systematic sequencing data is thus to elucidate the potential role of these
      elements in the regulation of nearby genes, and ultimately in the evolution of
      eukaryotic genomes.

PMID- 16093675
TI  - I elements in Drosophila: in vivo retrotransposition and regulation.

PMID- 16093676
TI  - The structures of mouse and human L1 elements reflect their insertion mechanism.
AB  - L1 is an abundant, interspersed repeated DNA element of mammalian genomes. It has
      achieved its high copy number via retrotransposition. Like other non-LTR
      retrotransposons, L1 insertion into chromosomal DNA apparently occurs by target
      site primed reverse transcription, or TPRT. L1 retrotransposition often generates
      elements with 5' truncations that are flanked by a duplication of the genomic
      target site (TSD). It is typically assumed that the 5' truncated elements are the
      consequence of poor processivity of the L1 reverse transcriptase. However, we
      find that the majority of young L1 elements from both the human and mouse genomes
      are truncated at sequences that can basepair with the target site. Thus, to
      whatever extent truncation is a consequence of poor processivity, we suggest that
      truncation is likely to occur when target site sequence can basepair with L1
      sequence. This finding supports a model for insertion that occurs by two
      sequential TPRT reactions, the second of which relies upon the homology between
      the target site and L1. Because perfect heteroduplex formation is not required
      for all insertions, a dynamic relationship between the primer, template and
      enzyme during reverse transcription is inferred. 5' truncation may be a
      successful evolutionary strategy that is exploited by L1 as a means to escape
      host suppression of transposition.

PMID- 16093677
TI  - Stress activation and genomic impact of Tnt1 retrotransposons in Solanaceae.
AB  - Tnt1 elements are a superfamily of LTR-retrotransposons distributed in the
      Solanaceae plant family and represent good model systems for studying regulatory
      and evolutionary controls established between hosts and transposable elements.
      Tnt1 retrotransposons tightly control their activation, by restricting expression
      to specific conditions. The Tnt1A element, originally discovered in tobacco, is
      expressed in response to stress, and its activation by microbial factors is
      followed by amplification, demonstrating that factors of pathogen origin can
      generate genetic diversity in plants. The Tnt1A promoter has the potential to be
      activated by various biotic and abiotic stimuli but a number of these are
      specifically repressed in tobacco and are revealed only when the LTR promoter is
      placed in a heterologous context. We propose that a tobacco- and stimulus
      specific repression has been established in order to minimize activation in
      conditions that might generate germinal transposition. In addition to tight
      transcriptional controls, Tnt1A retrotransposons self-regulate their activity
      through gradual generation of defective copies that have reduced transcriptional
      activity. Tnt1 retrotransposons found in various Solanaceae species are
      characterized by a high level of variability in the LTR sequences involved in
      transcription, and have evolved by gaining new expression patterns, mostly
      associated with responses to diverse stress conditions. Tnt1A insertions
      associated with genic regions are initially favored but seem subsequently counter
      selected, while insertions in repetitive DNA are maintained. On the other hand,
      amplification and loss of insertions may result from more brutal occurrences, as
      suggested by the large restructuring of Tnt1 populations observed in tobacco
      compared to each of its parental species. The distribution of Tnt1 elements thus
      appears as a dynamic flux, with amplification counterbalanced by loss of
      insertions. Tnt1 insertion polymorphisms are too high to reveal species
      relationships in the Nicotiana genus, but can be used to evaluate species
      relationships in the Lycopersicon and Capsicum genera. This also demonstrates
      that the behavior of Tnt1 retrotransposons differs between host species, most
      probably in correlation to differences in expression conditions and in the
      evolutionary and environmental history of each host.

PMID- 16093678
TI  - Host defenses to transposable elements and the evolution of genomic imprinting.
AB  - Genomic imprinting is the differential expression of maternally and paternally
      inherited alleles of specific genes. Several organismic level hypotheses have
      been offered to explain the evolution of genomic imprinting. We argue that
      evolutionary explanations of the origin of imprinting that focus exclusively on
      the organismic level are incomplete. We propose that the complex molecular
      mechanisms that underlie genomic imprinting originally evolved as an adaptive
      response to the mutagenic potential of transposable elements (TEs). We also
      present a model of how these mechanisms may have been co-opted by natural
      selection to evolve molecular features characteristic of genomic imprinting.

PMID- 16093679
TI  - APE-type non-LTR retrotransposons: determinants involved in target site
      recognition.
AB  - Non-long terminal repeat (Non-LTR) retrotransposons represent a diverse and
      widely distributed group of transposable elements and an almost ubiquitous
      component of eukaryotic genomes that has a major impact on evolution. Their copy
      number can range from a few to several million and they often make up a
      significant fraction of the genomes. The members of the dominating subtype of non
      LTR retrotransposons code for an endonuclease with homology to
      apurinic/apyrimidinic endonucleases (APE), and are thus termed APE-type non-LTR
      retrotransposons. In the last decade both the number of identified non-LTR
      retrotransposons and our knowledge of biology and evolution of APE-type non-LTR
      retrotransposons has increased tremendously.

PMID- 16093680
TI  - Reverse transcriptase and integrase of the Saccharomyces cerevisiae Ty1 element.
AB  - Integrase (IN) and reverse transcriptase (RT) play a central role in
      transposition of retroelements. The mechanism of integration by IN and the steps
      of the replication process mediated by RT are briefly described here. Recently,
      active recombinant forms of Ty1 IN and RT have been obtained. This has allowed a
      more detailed understanding of their biochemical and structural properties and
      has made possible combined in vitro and in vivo analyses of their functions. A
      focus of this review is to discuss some of the results obtained thus far with
      these two recombinant proteins and to propose future directions.

PMID- 16093681
TI  - Transfer RNA gene-targeted integration: an adaptation of retrotransposable
      elements to survive in the compact Dictyostelium discoideum genome.
AB  - Almost every organism carries along a multitude of molecular parasites known as
      transposable elements (TEs). TEs influence their host genomes in many ways by
      expanding genome size and complexity, rearranging genomic DNA, mutagenizing host
      genes, and altering transcription levels of nearby genes. The eukaryotic
      microorganism Dictyostelium discoideum is attractive for the study of fundamental
      biological phenomena such as intercellular communication, formation of
      multicellularity, cell differentiation, and morphogenesis. D. discoideum has a
      highly compacted, haploid genome with less than 1 kb of genomic DNA separating
      coding regions. Nevertheless, the D. discoideum genome is loaded with 10% of TEs
      that managed to settle and survive in this inhospitable environment. In depth
      analysis of D. discoideum genome project data has provided intriguing insights
      into the evolutionary challenges that mobile elements face when they invade
      compact genomes. Two different mechanisms are used by D. discoideum TEs to avoid
      disruption of host genes upon retrotransposition. Several TEs have invented the
      specific targeting of tRNA gene-flanking regions as a means to avoid integration
      into coding regions. These elements have been dispersed on all chromosomes,
      closely following the distribution of tRNA genes. By contrast, TEs that lack bona
      fide integration specificities show a strong bias to nested integration, thus
      forming large TE clusters at certain chromosomal loci that are hardly resolved by
      bioinformatics approaches. We summarize our current view of D. discoideum TEs and
      present new data from the analysis of the complete sequences of D. discoideum
      chromosomes 1 and 2, which comprise more than one third of the total genome.

PMID- 16093682
TI  - Competition between R1 and R2 transposable elements in the 28S rRNA genes of
      insects.
AB  - R1 and R2 are non-LTR retrotransposons that insert in the 28S rRNA genes of
      arthropods. R1 elements insert into a site that is 74 bp downstream of the R2
      insertion site, thus the presence of an R2 in the same 28S gene may inhibit the
      expression of R1. Consistent with such a suggestion, the R1 elements of
      Drosophila melanogaster have a strong bias against inserting into 28S genes
      already containing an R2 element. R2 elements, on the other hand, are only 2-3
      fold inhibited from inserting into a 28S gene already containing an R1. D.
      melanogaster R1 elements are unusual in that they generate a 23-bp deletion of
      the target site upstream of the insertion. Using in vitro assays developed to
      study R2 integration, we show that the presence of R1 sequences 51 bp downstream
      of the R2 insertion site changes the nucleosomal structure that can be formed by
      the R2 target site. The R2 endonuclease is inhibited from cleaving these altered
      nucleosomes. We suggest that R1 elements have been selected to make this large
      deletion of the 28S gene to block the insertion of an upstream R2 element. These
      findings are consistent with the model that R1 and R2 are in competition for the
      limited number of insertion sites available within their host's genome.

PMID- 16093683
TI  - A family of neofunctionalized Ty3/gypsy retrotransposon genes in mammalian
      genomes.
AB  - A family of at least eleven genes called Mar related to long terminal repeat
      retrotransposons from the Ty3/gypsy group, including two genes previously
      identified as such, is present in human and mouse genomes. Single orthologous
      copies were identified for most Mar genes in different mammals. All of them have
      lost essential structural features necessary for autonomous retrotransposition
      before divergence between mouse and human. Three Mar genes also have introns at
      identical positions in human and mouse. Hence, Mar genes do not correspond to
      functional retrotransposons. Mar genes evolved under purifying selection,
      strongly suggesting that they are not pseudogenic relics but rather
      neofunctionalized retrotransposon genes. All putative Mar proteins display
      sequence similarity to the capsid-like domain of the Gag protein of Tf1/Sushi
      retrotransposons. In addition, three Mar proteins have conserved the Gag CCHC
      zinc finger motif, suggesting a role in nucleic acid binding. Some Mar genes have
      also retained from their retrotransposon origin a -1 ribosomal frameshifting
      between the gag-related open reading frame and a region encoding a putative
      aspartyl protease domain. EST analysis revealed that the majority of Mar genes
      are expressed in brain as well as in other tissues and organs. Some Mar proteins
      might function as transcription factors or be involved in the control of cell
      proliferation and apoptosis. Strikingly, as many as eight Mar genes are located
      on the X chromosome in human, mouse and other mammals, and at least two of the
      autosomal genes are subject to imprinting. We suggest that retrotransposons might
      be a source for epigenetically regulated genes. Epigenetic regulation of these
      neogenes might be derived from the cellular defense mechanisms having controlled
      their retrotransposon ancestor.

PMID- 16093684
TI  - Human endogenous retroviruses: from infectious elements to human genes.
AB  - Mammalian genomes contain a heavy load (42% in humans) of retroelements, which
      are mobile sequences requiring reverse transcription for their replicative
      transposition. A significant proportion of these elements is of retroviral
      origin, with thousands of sequences resembling the integrated form of infectious
      retroviruses, with two LTRs bordering internal regions homologous to the gag,
      prt, pol, and env genes. These elements, named endogenous retroviruses (ERVs),
      are most probably the proviral remnants of ancestral germ-line infections by
      active retroviruses, which have thereafter been transmitted in a Mendelian
      manner. The complete sequencing of the human genome now allows a comprehensive
      survey of human ERVs (HERVs), which can be grouped according to sequence
      homologies into approximately 80 distinct families, each containing a few to
      several hundred elements. As reviewed here, strong similarities between HERVs and
      present-day retroviruses can be inferred from phylogenetic analyses on the
      reverse transcriptase (RT) domain of the pol gene or the transmembrane subunit
      (TM) of the env gene, which disclose interspersion of both classes of elements
      and suggest a common history and shared ancestors. Similarities are also observed
      at the functional levels, since despite the fact that most HERVs have accumulated
      mutations, deletions, and/or truncations, several elements still possess some of
      the functions of retroviruses, with evidence for viral-like particle formation,
      and occurrence of envelope proteins allowing cell-cell fusion and even conferring
      infectivity to pseudotypes. Along this line, a genomewide screening for human
      retroviral genes with coding capacity has revealed 16 fully coding envelope
      genes. These genes are transcribed in several healthy tissues including the
      placenta, three of them at a very high level. Besides their impact in modelling
      the genome, HERVs thus appear to contain still active genes, which most probably
      have been subverted by the host for its benefit and should be considered as bona
      fide human genes. Some of their characteristic features and possible
      physiological roles, as well as potential pathological effects inherited from
      their retroviral ancestors are also reviewed.

PMID- 16093685
TI  - Transposable elements donate lineage-specific regulatory sequences to host
      genomes.
AB  - The evolutionary implications of transposable element (TE) influences on gene
      regulation are explored here. An historical perspective is presented to
      underscore the importance of TE influences on gene regulation with respect to
      both the discovery of TEs and the early conceptualization of their potential
      impact on host genome evolution. Evidence that points to a role for TEs in host
      gene regulation is reviewed, and comparisons between genome sequences are used to
      demonstrate the fact that TEs are particularly lineage-specific components of
      their host genomes. Consistent with these two properties of TEs, regulatory
      effects and evolutionary specificity, human-mouse genome wide sequence
      comparisons reveal that the regulatory sequences that are contributed by TEs are
      exceptionally lineage specific. This suggests a particular mechanism by which TEs
      may drive the diversification of gene regulation between evolutionary lineages.

PMID- 16093686
TI  - Impact of transposable elements on the evolution of mammalian gene regulation.
AB  - Transposable elements (TEs) are present in all organisms and nearly half of the
      human and mouse genome is derived from ancient transpositions. This fact alone
      suggests that TEs have played a major role in genome organization and evolution.
      Studies undertaken over the last two decades or so clearly show that TEs of
      various kinds have played an important role in organism evolution. Here we review
      the impact TEs have on the evolution of gene regulation and gene function with an
      emphasis on humans. Understanding the mechanisms resulting in genomic change is
      central to our understanding of gene regulation, genetic disease and genome
      evolution. Full comprehension of these biological processes is not possible
      without an in depth knowledge of how TEs impact upon the genome.

PMID- 16093687
TI  - Endogenous retroviruses and animal reproduction.
AB  - Endogenous retroviruses (ERV), as part of the host genetic heritage, are
      transmissible to the next generation in a Mendelian way. Their abundance in
      animal genomes and their expression primarily detected in germ cells, embryonic
      tissues and cancer cell lines, raised the question of their biological
      significance. This article reviews the possible role of ERVs in the physiology
      and diseases of animal reproduction, from Drosophila to human. In males, there is
      no trivial involvement of ERVs in a physiological process. Conversely, a
      spermatogenesis defect was associated in the human male with HERV-K expression
      and HERV15-induced chromosomal alteration, leading to cancer and infertility,
      respectively. In females, the study of insect ERVs (IERV) pointed out the overlap
      between genetics and virology with the genetic-dependent regulation of ZAM and
      the non-infectious and infectious life cycles of gypsy. The pattern of ERVs
      expression in rodent, ovine and human females suggest a hormone-dependent
      mechanism consistent with the mammalian oestrus cycle regulation. The
      differentiation of the mammary epithelium and breast tumorigenesis involving the
      mouse mammary tumour viruses (MMTV) illustrate the intimate connection between
      endogenous and exogenous retroviruses. Last, as a major site of ERVs
      transcription, placenta contributed to our understanding of ERVs modulation of
      neighbouring gene expression. As an interface, i.e. a site of conflicts and
      exchanges, placenta should resist infection and protect the foetus against the
      maternal immune system. Retroviral envelopes could theoretically provide such
      features due to receptor interference, immunosuppression and fusion properties,
      as shown by the HERV-W envelope involved in the syncytiotrophoblast formation. We
      conclude with an insight on the evolutionary and epigenetic consequences of the
      relationships of ERV guests with their animal hosts.

PMID- 16093688
TI  - Human retroelements may introduce intragenic polyadenylation signals.
AB  - In the human genome, the insertion of LINE-1 and Alu elements can affect genes by
      sequence disruption, and by the introduction of elements that modulate the gene's
      expression. One of the modulating sequences retroelements may contribute is the
      canonical polyadenylation signal (pA), AATAAA. L1 elements include these within
      their own sequence and AATAAA sequences are commonly created in the A-rich tails
      of both SINEs and LINEs. Computational analysis of 34 genes randomly retrieved
      from the human genome draft sequence reveals an orientation bias, reflected as a
      lower number of L1s and Alus containing the pA in the same orientation as the
      gene. Experimental studies of Alu-based pA sequences when placed in pol II or pol
      III transcripts suggest that the signal is very weak, or often not used at all.
      Because the pA signal is highly affected by the surrounding sequence, it is
      likely that the Alu constructs evaluated did not provide the required recognition
      signals to the polyadenylation machinery. Although the effect of pA signals
      contributed by Alus is individually weak, the observed reduction of "sense"
      oriented pA-containing L1 and Alu elements within genes reflects that even a
      modest influence causes a change in evolutionary pressure, sufficient to create
      the biased distribution.

PMID- 16093689
TI  - Mobile genetic elements and sexual reproduction.
AB  - Transposable elements (TE) are prominent components of most eukaryotic genomes.
      In addition to their possible participation in the origin of sexual reproduction
      in eukaryotes, they may be also involved in its maintenance as important
      contributors to the deleterious mutation load. Comparative analyses of transposon
      content in the genomes of sexually reproducing and anciently asexual species may
      help to understand the contribution of different TE classes to the deleterious
      load. The apparent absence of deleterious retrotransposons from the genomes of
      ancient asexuals is in agreement with the hypothesis that they may play a special
      role in the maintenance of sexual reproduction and in early extinction for which
      most species are destined upon the abandonment of sex.

PMID- 16093690
TI  - Evolutionary forces generating sequence homogeneity and heterogeneity within
      retrotransposon families.
AB  - Genome projects allow us to sample copies of a retrotransposon sequence family
      residing in a host genome. The variation in DNA sequence between these individual
      copies will reflect the evolutionary process that has spread the sequences
      through the genome. Here I review quantitatively the expected diversity of
      elements belonging to a transposable genetic element family. I use a simple
      neutral model for replicative mobile DNAs such as retrotransposons to predict the
      extent of sequence variability between members of a single family of transposable
      elements, both within and between species. The effects of horizontal transfer are
      also explored. I also consider the impact on these distributions of an increase
      in transposition rate arising from a mutational change in copy of the sequence.
      In addition, I consider the question of the interaction between retrotransposons
      and their hosts, and the causes of the abundance of transposable elements in the
      genomes that they occupy.

PMID- 16093691
TI  - Ribonuclease H evolution in retrotransposable elements.
AB  - Eukaryotic and prokaryotic genomes encode either Type I or Type II Ribonuclease H
      (RNH) which is important for processing RNA primers that prime DNA replication in
      almost all organisms. This review highlights the important role that Type I RNH
      plays in the life cycle of many retroelements, and its utility in tracing early
      events in retroelement evolution. Many retroelements utilize host genome-encoded
      RNH, but several lineages of retroelements, including some non-LTR retroposons
      and all LTR retrotransposons, encode their own RNH domains. Examination of these
      RNH domains suggests that all LTR retrotransposons acquired an enzymatically weak
      RNH domain that is missing an important catalytic residue found in all other RNH
      enzymes. We propose that this reduced activity is essential to ensure correct
      processing of the polypurine tract (PPT), which is an important step in the life
      cycle of these retrotransposons. Vertebrate retroviruses appear to have
      reacquired their RNH domains, which are catalytically more active, but their
      ancestral RNH domains (found in other LTR retrotransposons) have degenerated to
      give rise to the tether domains unique to vertebrate retroviruses. The tether
      domain may serve to control the more active RNH domain of vertebrate
      retroviruses. Phylogenetic analysis of the RNH domains is also useful to "date"
      the relative ages of LTR and non-LTR retroelements. It appears that all LTR
      retrotransposons are as old as, or younger than, the "youngest" lineages of non
      LTR retroelements, suggesting that LTR retrotransposons arose late in eukaryotes.

PMID- 16093692
TI  - The recent evolution of human L1 retrotransposons.
AB  - L1 elements are the most successful retrotransposons in mammals and are
      responsible for at least 30% of human DNA. Far from being indolent genomic
      parasites, L1 elements have evolved and amplified rapidly during human evolution.
      Indeed during just the last 25 million years (MY) five distinct L1 families have
      emerged and generated tens of thousands of copies. The most recently evolved
      human specific L1 family is currently active and L1 copies have been accumulating
      in the human genome at about the same rate per generation as the currently active
      L1 families in Old World rats and mice. At times during the last 25 MY L1
      activity constituted a significant enough genetic load to be subject to negative
      selection. During these same times, and in apparent response to the host, L1
      underwent adaptive evolution. Understanding the molecular basis for these
      evolutionary changes should help illuminate one of the least understood but most
      important aspects of L1 biology, namely the extent and nature of the interaction
      between L1 and its host.

PMID- 16093693
TI  - Extinction of LINE-1 activity coincident with a major mammalian radiation in
      rodents.
AB  - LINE-1 transposable elements (L1s) are ubiquitous in mammals and are thought to
      have remained active since before the mammalian radiation. Only one L1 extinction
      event, in South American rodents in the genus Oryzomys, has been convincingly
      demonstrated. Here we examine the phylogenetic limits and evolutionary tempo of
      that extinction event by characterizing L1s in related rodents. Fourteen genera
      from five tribes within the Sigmodontinae subfamily were examined. Only the
      Sigmodontini, the most basal tribe in this group, demonstrate recent L1 activity.
      The Oryzomyini, Akodontini, Phyllotini, and Thomasomyini contain only L1s that
      appear to have inserted long ago; their L1s lack open reading frames, have
      mutations at conserved amino acid residues, and show numerous private mutations.
      They also lack restriction site-defined L1 subfamilies specific to any species,
      genus or tribe examined, and fail to form monophyletic species, genus or tribal
      L1 clusters. We determine here that this L1 extinction event occurred roughly 8.8
      million years ago, near the divergence of Sigmodon from the remaining
      Sigmodontinae species. These species appear to be ideal model organisms for
      studying the impact of L1 inactivity on mammalian genomes.

PMID- 16093694
TI  - SINE extinction preceded LINE extinction in sigmodontine rodents: implications
      for retrotranspositional dynamics and mechanisms.
AB  - Short Interspersed Nuclear Elements, or SINEs, retrotranspose despite lacking
      protein-coding capability. It has been proposed that SINEs utilize enzymes
      produced in trans by Long Interspersed Nuclear Elements, or LINEs. Strong support
      for this hypothesis is found in LINE and SINE pairs that share sequence homology;
      however, LINEs and SINEs in primates and rodents are only linked by an insertion
      site motif. We have now profiled L1 LINE and B1 SINE activity in 24 rodent
      species including candidate taxa for the first documented L1 extinction. As
      expected, there was no evidence for recent activity of B1s in species that also
      lack L1 activity. However, B1 silencing appears to have preceded L1 extinction,
      since B1 activity is also lacking in the genus most closely related to those
      lacking active L1s despite the presence of active L1s in this genus. A second
      genus with active L1s but inactive B1s was also identified.

PMID- 16093695
TI  - Abundance, distribution and dynamics of retrotransposable elements and
      transposons: similarities and differences.
AB  - Retrotransposable elements and transposons are generally both found in most
      eukaryotes. These two classes of elements are usually distinguished on the basis
      of their differing mechanisms of transposition. However, their respective
      frequencies, their intragenomic dynamics and distributions, and the frequencies
      of their horizontal transfer from one species to another can also differ. The
      main objective of this review is to compare these two types of elements from a
      new perspective, using data provided by genome sequencing projects and relating
      this to the theoretical and observed dynamics. It is shown that the traditional
      division into two classes, based on the transposition mechanisms, becomes less
      obvious when other factors are taken into consideration. A great diversity in
      distribution and dynamics within each class is observed. In contrast, the impact
      on and the interactions with the genome can show striking similarities between
      families of the two classes.

PMID- 16093696
TI  - Comparative evolution history of SINEs in Arabidopsis thaliana and Brassica
      oleracea: evidence for a high rate of SINE loss.
AB  - Brassica oleracea and Arabidopsis thaliana belong to the Brassicaceae(Cruciferae)
      family and diverged 16 to 19 million years ago. Although the genome size of B.
      oleracea (approximately 600 million base pairs) is more than four times that of
      A. thaliana (approximately 130 million base pairs), their gene content is
      believed to be very similar with more than 85% sequence identity in the coding
      region. Therefore, this important difference in genome size is likely to reflect
      a different rate of non-coding DNA accumulation. Transposable elements (TEs)
      constitute a major fraction of non-coding DNA in plant species. A different rate
      in TE accumulation between two closely related species can result in significant
      genome size variations in a short evolutionary period. Short interspersed
      elements (SINEs) are non-autonomous retroposons that have invaded the genome of
      most eukaryote species. Several SINE families are present in B. oleracea and A.
      thaliana and we found that two of them (called RathE1 and RathE2) are present in
      both species. In this study, the tempo of evolution of RathE1 and RathE2 SINE
      families in both species was compared. We observed that most B. oleracea RathE2
      SINEs are "young" (close to the consensus sequence) and abundant while elements
      from this family are more degenerated and much less abundant in A. thaliana.
      However, the situation is different for the RathE1 SINE family for which the
      youngest elements are found in A. thaliana. Surprisingly, no SINE was found to
      occupy the same (orthologous) genomic locus in both species suggesting that
      either these SINE families were not amplified at a significant rate in the common
      ancestor of the two species or that older elements were lost and only the recent
      (lineage-specific) insertions remain. To test this latter hypothesis, loci
      containing a recently inserted SINE in the A. thaliana col-0 ecotype were
      selected and characterized in several other A. thaliana ecotypes. In addition to
      the expected SINE containing allele and the pre-integrative allele (i.e. the
      "empty" allele), we observed in the different ecotypes, alleles with truncated
      portions of the SINE (up to the complete loss of the element) and of the
      immediate genomic flanking sequences. The absence of SINEs in orthologous
      positions between B. oleracea and A. thaliana and the presence in recently
      diverged A. thaliana ecotypes of alleles containing severely truncated SINEs
      suggest a very high rate of SINE loss in these species.

PMID- 16093697
TI  - Human endogenous retroviruses in the primate lineage and their influence on host
      genomes.
AB  - Primates emerged about 60 million years ago. Since that time various primate
      targeting retroviruses have integrated in the germ line of primate species, and
      some drifted to fixation. After germ line fixation, continued activity of
      proviruses resulted in intragenomic spread of so-called endogenous retroviruses
      (ERVs). Variant ERVs emerged, amplified in the genome and profoundly altered
      genome structures and potentially functionality. Importantly, ERVs are genome
      modifiers of exogenous origin. The human genome contains about 8% of sequences of
      retroviral origin. The human ERVs (HERVs) comprise many distinct families that
      amplified to copy numbers of up to several thousand. We review here the evolution
      of several well-characterized HERV families in the human lineage since initial
      germ line fixation. It is apparent that endogenous retroviruses profoundly
      affected the genomes of species in the evolutionary lineage leading to Homo
      sapiens.

PMID- 16093698
TI  - Classification and nomenclature of retrotransposable elements.
AB  - The classification and nomenclature of retrotransposable elements is reviewed. A
      comparison is made between the initial classification summarized in Capy et al.
      (1997b), and the more recent proposal based on the classification of the viruses
      (Hull, 2001). Several problems, mainly relating to the position of elements
      belonging to the DIRS-like or Bel-like groups, are discussed. The first
      classification is now out of date, and must be revisited to take account of the
      discovery of new elements, however the second cannot be extended to the DNA
      elements. There is therefore, clear evidence of the need to adopt a general and a
      common classification.

PMID- 16093699
TI  - Repbase Update, a database of eukaryotic repetitive elements.
AB  - Repbase Update is a comprehensive database of repetitive elements from diverse
      eukaryotic organisms. Currently, it contains over 3600 annotated sequences
      representing different families and subfamilies of repeats, many of which are
      unreported anywhere else. Each sequence is accompanied by a short description and
      references to the original contributors. Repbase Update includes Repbase Reports,
      an electronic journal publishing newly discovered transposable elements, and the
      Transposon Pub, a web-based browser of selected chromosomal maps of transposable
      elements. Sequences from Repbase Update are used to screen and annotate
      repetitive elements using programs such as Censor and RepeatMasker. Repbase
      Update is available on the worldwide web at
      http://www.girinst.org/Repbase_Update.html.

PMID- 16093700
TI  - Genome-wide experimental identification and functional analysis of human specific
      retroelements.
AB  - Retroelements (REs) actively reshape genomes through genomic rearrangements,
      creation of new genes and modulation of the regulatory machinery of existing
      genes, thus introducing genomic novelties which potentially may be subject to
      natural selection. Thousands of RE integrations, presumably distinguishing the
      human and chimpanzee genomes, might well be involved in modern human speciation.
      In this self-review we describe our recent results on genome-wide identification
      of human specific RE integrations and their transcriptional activity obtained
      with three new experimental techniques (TGDA, DiffIR and SDDIR) developed by us
      for such studies. A new mechanism of the formation of retroelements involving
      template switches during L1-mediated mRNA reverse transcription, revealed in this
      research, will also be described in the review.

PMID- 16093701
TI  - SINEs and LINEs: symbionts of eukaryotic genomes with a common tail.
AB  - Many SINEs and LINEs have been characterized to date, and examples of the SINE
      and LINE pair that have the same 3' end sequence have also increased. We report
      the phylogenetic relationships of nearly all known LINEs from which SINEs are
      derived, including a new example of a SINE/LINE pair identified in the salmon
      genome. We also use several biological examples to discuss the impact and
      significance of SINEs and LINEs in the evolution of vertebrate genomes.

PMID- 16093702
TI  - Retrons, msDNA, and the bacterial genome.
AB  - Retrons are distinct DNA sequences that code for a reverse transcriptase (RT)
      similar to the RTs produced by retroviruses and other types of retroelements.
      Retron DNAs are commonly associated with prophage DNA and are found in the
      genomes of a wide variety of different bacteria. The retron RT is used to
      synthesize a strange satellite DNA known as msDNA. msDNA is actually a complex of
      DNA, RNA, and probably protein. It is composed of a small, single-stranded DNA,
      linked to a small, single-stranded RNA molecule. The 5' end of the DNA molecule
      is joined to an internal guanosine residue of the RNA molecule by a unique 2'-5'
      phosphodiester bond. msDNA is produced in many hundreds of copies per cell, but
      its function remains unknown. Although retrons are absent from the genome of most
      members of a population of related bacteria, retrons may not be entirely benign
      DNAs. Evidence is beginning to suggest that retron elements may produce small but
      potentially significant effects on the host cell. This includes the generation of
      repeated copies of the msDNA sequence in the genome, and increasing the frequency
      of spontaneous mutations. Because these events involve the retron RT, this may
      represent a source of reverse transcription in the bacterial cell. Thus, the
      process of reverse transcription, a force that has profoundly affected the
      content and structure of most eukaryotic genomes, may likewise be responsible for
      changes in some prokaryotic genomes.

PMID- 16093703
TI  - Transposable elements in mosquitoes.
AB  - We describe the current state of knowledge about transposable elements (TEs) in
      different mosquito species. DNA-based elements (class II elements), non-LTR
      retrotransposons (class I elements), and MITEs (Miniature Inverted Repeat
      Transposable Elements) are found in the three genera, Anopheles, Aedes and Culex,
      whereas LTR retrotransposons (class I elements) are found only in Anopheles and
      Aedes. Mosquitoes were the first insects in which MITEs were reported; they have
      several LTR retrotransposons belonging to the Pao family, which is distinct from
      the Gypsy-Ty3 and Copia-Ty1 families. The number of TE copies shows huge
      variations between classes of TEs within a given species (from 1 to 1000), in
      sharp contrast to Drosophila, which shows only relatively minor differences in
      copy number between elements (from 1 to 100). The genomes of these insects
      therefore display major differences in the amount of TEs and therefore in their
      structure and global composition. We emphasize the need for more population
      genetic data about the activity of TEs, their distribution over chromosomes and
      their frequencies in natural populations of mosquitoes, to further the current
      attempts to develop a transgenic mosquito unable to transmit malaria that is
      intended to replace the natural populations.

PMID- 16093704
TI  - Penelope-like elements--a new class of retroelements: distribution, function and
      possible evolutionary significance.
AB  - Here we describe a new class of retroelements termed PLE (Penelope-like
      elements). The only transpositionally active representative of this lineage found
      so far has been isolated from Drosophila virilis. This element, Penelope, is
      responsible for the hybrid dysgenesis syndrome in this species, characterized by
      simultaneous mobilization of several unrelated TE families in the progeny of
      dysgenic crosses. Several lines of evidence favor the hypothesis of recent
      Penelope invasion into D. virilis. Moreover, when D. virilisPenelope was
      introduced by P element-mediated transformation into the genome of D.
      melanogaster, it underwent extensive amplification in the new host and induced
      several traits of the dysgenesis syndrome, including gonadal atrophy and numerous
      mutations. The single ORF encoded by PLE consists of two principal domains:
      reverse transcriptase (RT) and endonuclease (EN), which is similar to GIY-YIG
      intron-encoded endonucleases. With the appearance of a large number of PLEs in
      genome databases from diverse eukaryotes, including amoebae, fungi, cnidarians,
      rotifers, flatworms, roundworms, fish, amphibia, and reptilia, it becomes
      possible to resolve their phylogenetic relationships with other RT groups with a
      greater degree of confidence. On the basis of their peculiar structural features,
      distinct phylogenetic placement, and structure of transcripts, we conclude that
      PLE constitute a novel class of eukaryotic retroelements, different from non-LTR
      and LTR retrotransposons.

PMID- 16093705
TI  - Diversity and clustered distribution of retrotransposable elements in the compact
      genome of the pufferfish Tetraodon nigroviridis.
AB  - We report the characterization and chromosomal distribution of retroelements in
      the compact genome of the pufferfish Tetraodon nigroviridis. We have
      reconstructed partial/complete retroelement sequences, established their
      phylogenetic relationship to other known eukaryotic retrotransposons, and
      performed double-color FISH analyses to gain new insights into their patterns of
      chromosomal distribution. We could identify 43 different reverse transcriptase
      retrotransposons belonging to the three major known subclasses (14 non-LTR
      retrotransposons from seven clades, 25 LTR retrotransposons representing the five
      major known groups, and four Penelope-like elements), and well as two SINEs (non
      autonomous retroelements). Such a diversity of retrotransposable elements, which
      seems to be relatively common in fish but not in mammals, is astonishing in such
      a compact genome. The total number of retroelements was approximately 3000,
      roughly representing only 2.6% of the genome of T. nigroviridis. This is much
      less than in other vertebrate genomes, reflecting the compact nature of the
      genome of this pufferfish. Major differences in copy number were observed between
      different clades, indicating differential success in invading and persisting in
      the genome. Some retroelements displayed evidence of recent activity. Finally,
      FISH analysis showed that retrotransposable elements preferentially accumulate in
      specific heterochromatic regions of the genome of T. nigroviridis, revealing a
      degree of genomic compartmentalization not observed in the human genome.

PMID- 16093706
TI  - The Alu Yc1 subfamily: sorting the wheat from the chaff.
AB  - Members of the Alu Yc1 subfamily are distinguished from the older Alu Y subfamily
      by a signature G-->A substitution at base 148 of their 281-bp consensus sequence.
      Members of the much older and larger Alu Y subfamily could have by chance
      accumulated this signature G-->A substitution and be misclassified as belonging
      to the Alu Yc1 subfamily. Using a Mahanalobis classification method, it was
      estimated that the "authentic" Alu Yc1 subfamily consists of approximately 262
      members in the human genome. PCR amplification and further analysis was
      successfully completed on 225 of the Yc1 Alu family members. One hundred and
      seventy-seven Yc1 Alu elements were determined to be monomorphic (fixed for
      presence) in a panel of diverse human genomes. Forty-eight of the Yc1 Alu
      elements were polymorphic for insertion presence/absence in diverse human
      genomes. The insertion polymorphism rate of 21% in the human genome is similar to
      rates reported previously for other "young" Alu subfamilies. The polymorphic Yc1
      Alu elements will be useful genetic loci for the study of human population
      genetics.

PMID- 16093707
TI  - Phylogenomic analysis of chromoviruses.
AB  - Genome sequences of model organisms provide a unique opportunity to obtain
      insight into the complete diversity of any transposable element (TE) group. A
      limited number of chromoviruses, the chromodomain containing genus of
      Metaviridae, is known from plant, fungal and vertebrate genomes. By searching
      diverse eukaryotic genome databases, we have found a surprisingly large number of
      new, structurally intact and highly conserved chromoviral elements, greatly
      exceeding the number of previously known chromoviruses. In this study, we
      examined the diversity, origin and evolution of chromoviruses in Eukaryota.
      Chromoviral diversity in plants, fungi and vertebrates, as shown by phylogenetic
      analyses, was found to be much greater than previously expected. A novel
      centromere-specific chromoviral lineage was found to be widespread and highly
      conserved in all seed plants. The age of chromoviruses has been significantly
      extended by finding their representatives in the most basal plant lineages (green
      and red algae), in Heterokonta (oomycetes) and in Cercozoa (plasmodiophorids).
      The evolutionary origin of chromoviruses has been found to be no earlier than in
      Cercozoa, since none can be found in the basal eukaryotic lineages, despite the
      extensive genome data. The evolutionary dynamics of chromoviruses can be
      explained by a strict vertical transmission in plants and fungi, while in Metazoa
      it is more complex. The currently available genome data clearly show that
      chromoviruses are the most widespread and one of the oldest Metaviridae clade.

PMID- 16093708
TI  - Abyss1: a novel L2-like non-LTR retroelement of the snakelocks anemone (Anemonia
      sulcata).
AB  - Non-LTR retrotransposons are a diverse and taxonomically widely dispersed group
      of retroelements that can be divided into at least 14 distinguishable clades.
      Basal metazoans have not been examined in great detail for their retrotransposon
      content. In order to screen for the presence of reverse transcriptase (RT)
      related sequences in Cnidaria and Ctenophora, basal phyla of metazoans, PCR with
      highly degenerate oligonucleotides was performed and an RT-like sequence was
      identified from the sea anemone species Anemonia sulcata. Further screening
      identified a related element in another anemone species Actinia equina.
      Significant homology to non-LTR retrotransposon RTs was observed, particularly to
      L2-like elements of fish such as Maui. The sequence was not detected among other
      cnidarians and we have designated the A. sulcata and A. equina elements Abyss1
      and Abyss2 respectively. Phylogenetic analysis of Abyss1 compared with members of
      14 known non-LTR retroelement clades suggests that the sequence represents a
      novel L2 element.

PMID- 16093709
TI  - Characterisation of pararetrovirus-like sequences in the genome of potato
      (Solanum tuberosum).
AB  - Three families of pararetrovirus-like sequences were isolated from the genome of
      potato using PCR of a characteristic fragment extending from the end of the
      transactivator domain. The potato pararetrovirus-like sequences are abundant in
      the nuclear genome of potato as demonstrated by their hybridisation to high
      molecular weight DNA in Southern transfers and by fluorescence in situ
      hybridisation. Sequencing of cloned PCR products demonstrated that the potato
      pararetrovirus-like sequences were similar to other pararetroviral sequences and
      also to some expressed sequences from tobacco and tomato, notably from callus and
      Agrobacterium-infected tissue. It is possible that the potato pararetroviral
      sequences defend against viral genes via silencing mechanisms, although, as in
      Petunia or banana, their transcription and recombination may cause infection
      under stress conditions.

PMID- 16093710
TI  - The evolution of transposons in Schizosaccharomyces pombe.
AB  - Recent studies of the LTR-retrotransposons of Schizosaccharomyces pombe have shed
      considerable light on their evolution and function. The sequencing of the S.
      pombe genome allowed analysis of its transposon content. This analysis provides
      information about the maintenance and loss of transposons in the genome. The
      results of transposition assays and biochemical analyses demonstrate that the N
      terminal protein of Tf1 is functionally equivalent to the Gag proteins of
      retroviruses and retrotransposons. Despite this conservation of function, the N
      terminal protein of Tf1 lacks any sequence similarity to other known Gag
      proteins. Sequence analysis and experimental data also indicate that the Tf1
      transposons of S. pombe target their integration into specific sites in the host
      genome. Transposition events resulting from the expression of Tf1 reveal a strong
      preference for intergenic regions, specifically at pol II promoters in a window
      100-400 bp upstream of open reading frames. The complete and partial copies of Tf
      transposons in the sequenced genome of S. pombe show the same association of
      integration with promoter regions. This body of work explores how the transposon
      interacts with the host, the balance between the transposons propagation and
      loss, and how different families of transposons evolve.

PMID- 16093711
TI  - DIRS-1 and the other tyrosine recombinase retrotransposons.
AB  - DIRS-1 is a retroelement from the slime mold Dictyostelium discoideum. Until
      recently only two related retrotransposons had been described: PAT from the
      nematode Panagrellus redivivus and Prt1 from the zygomycete fungus Phycomyces
      blakesleeanus. Analyses of the reverse transcriptase sequences encoded by these
      three elements suggested that they were closely related to each other and more
      distantly related to the Ty3/gypsy Long Terminal Repeat (LTR) retroelements. They
      have several unusual structural features that distinguish them from typical LTR
      elements. For instance, they each encode a tyrosine recombinase (YR), but not a
      DDE-type integrase or an aspartic protease. Although the DIRS-1-related elements
      are bordered by terminal repeats these differ from typical LTRs in a number of
      ways. In DIRS-1, for example, the terminal repeats are inverted (complementary),
      non-identical in sequence, and the outer edges of the terminal sequences are
      repeated (adjacent to each other) in the internal region. PAT has so-called
      "split" direct repeats in which the unrelated terminal sequences appear as direct
      repeats adjacent to each other in the internal region. The only repetition
      displayed by Prt1 is the presence of short inverted terminal repeats, but the
      sequenced copy of this element is believed to be a truncated version of an
      element with a structure resembling DIRS-1. The unusual structure of the terminal
      repeats of the DIRS1-like elements appears to be related to their replication via
      free circular intermediates. Site-specific recombination is believed to integrate
      the circle without creating duplications of the target sites. In recognition of
      these important distinctions it is proposed that the retrotransposons that encode
      tyrosine recombinases be called the tyrosine recombinase (or YR)
      retrotransposons. Recently a large number of additional YR retrotransposons have
      been described, including elements from fungi (zygomycetes and basidiomycetes),
      plants (green algae) and a wide range of animals including nematodes, insects,
      sea urchins, fish and amphibia, while remnants of elements related to DIRS-1
      occur in the human genome. The complete set of YR retrotransposons can be divided
      into two major groups, the DIRS elements and the Ngaro elements, the two groups
      forming distinct clades on phylogenetic trees based on alignments of RT/RH and
      recombinase sequences, and also having some structural distinctions. A third
      group of transposable elements, which we call Cryptons, also carry tyrosine
      recombinases. These elements do not encode a reverse transcriptase and so are
      believed to be DNA transposons not retrotransposons. They have been detected in
      several pathogenic fungi, including the basidiomycete Cryptococcus neoformans,
      and the ascomycetes Coccidioides posadasii and Histoplasma capsulatum. Sequence
      comparisons suggest that the Crypton YRs are related to those of the YR
      retrotransposons. We suggest that the YR retrotransposons arose from the
      combination of a Crypton-like YR DNA transposon and the RT/RH encoding sequence
      of a retrotransposon.

PMID- 16093712
TI  - Group II intron retroelements: function and diversity.
AB  - Group II introns are a class of retroelements capable of carrying out both self
      splicing and retromobility reactions. In recent years, the number of known group
      II introns has increased dramatically, particularly in bacteria, and the new
      information is altering our understanding of these intriguing elements. Here we
      review the basic properties of group II introns, and summarize the differences
      between the organellar and bacterial introns with regard to structures, insertion
      patterns and inferred behaviors. We also discuss the evolution of group II
      introns, as they are the putative ancestors of spliceosomal introns and possibly
      non-LTR retroelements, and may have played an important role in the development
      of eukaryote genomes.

PMID- 16093713
TI  - A movable feast: diverse retrotransposons and their contribution to barley genome
      dynamics.
AB  - Cellular genes comprise at most 5% of the barley genome; the rest is occupied
      primarily by retrotransposons. Retrotransposons move intracellularly by a
      replicative mechanism similar to that of retroviruses. We describe the major
      classes of retrotransposons in barley, including the two nonautonomous groups
      that were recently identified, and detail the evidence supporting our current
      understanding of their life cycle. Data from analyses of long contiguous segments
      of the barley genome, as well as surveys of the prevalence of full-length
      retrotransposons and their solo LTR derivatives in the genus Hordeum, indicate
      that integration and recombinational loss of retrotransposons are major factors
      shaping the genome. The sequence conservation and integrative capacity of barley
      retrotransposons have made them excellent sources for development of molecular
      marker systems.

PMID- 16093715
TI  - International Equine Gene Mapping Workshop Report: a comprehensive linkage map
      constructed with data from new markers and by merging four mapping resources.
AB  - A comprehensive male linkage map was generated by adding 359 new, informative
      microsatellites to the International Equine Gene Map half-sibling reference
      families and by combining genotype data from three independent mapping resources:
      a full sibling family created at the Animal Health Trust in Newmarket, United
      Kingdom, eight half-sibling families from Sweden and two half-sibling families
      from the University of California, Davis. Because the combined data were derived
      primarily from half-sibling families, only autosomal markers were analyzed. The
      map was constructed from a total of 766 markers distributed on the 31 equine
      chromosomes. It has a higher marker density than that of previously reported
      maps, with 626 markers linearly ordered and 140 other markers assigned to a
      chromosomal region. Fifty-nine markers (7%) failed to meet the criteria for
      statistical evidence of linkage and remain unassigned. The map spans 3,740 cM
      with an average distance of 6.3 cM between markers. Fifty-five percent of the
      intervals are < or = 5 cM and only 3% > or = 20 cM. The present map demonstrates
      the cohesiveness of the different data sets and provides a single resource for
      genome scan analyses and integration with the radiation hybrid map.

PMID- 16093716
TI  - The scoliosis (sco) mouse: a new allele of Pax1.
AB  - We describe the spontaneous mutant mouse scoliosis (sco) that carries a new
      allele of Pax1 (un-i, undulated intermediate). The Pax1(un-i) allele is lacking
      the 5'-flanking region and exon 1 to 4 which is mapped to nt -2636 to -640 and 
      272 to 4271 of the Pax1 gene. Homozygous mice show a mild form of the known
      phenotypes of other Pax1 mutants. Adult mice have a lumbar scoliosis and kinky
      tails. In homozygous embryos the skeleton ossifies early, ossification centers of
      the vertebral bodies are fused with the ossification centers of the pedicles.
      Neural arches and spinous processes are underdeveloped but the pedicles and
      transverse processes are overdeveloped which is in contrast to other Pax1
      mutants. In the scapula, the acromion is missing and the deltoid tuberosity of
      the proximal humerus is shortened and thickened. Among the inner organs the
      thymus development is affected. In late embryos, the thymus is small and
      thymocyte numbers are reduced. T-cell development from CD4- and CD8- double
      negative (DN) to CD4+ and CD8+ double positive (DP) is decelerated. The
      percentage of CD90+ cells is also reduced but in contrast to other Pax1 mutants
      no alteration of the expression level of the CD90 (Thy-1) could be found.

PMID- 16093717
TI  - Molecular cytogenetic insights into the ageing syndrome Hutchinson-Gilford
      Progeria (HGPS).
AB  - Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder
      characterized by premature ageing in childhood and serves as a valuable model for
      the human ageing process in general. Most recently, point mutations in the lamin
      A (LMNA) gene on chromosome 1q have been associated with the disease, however how
      these mutations relate to the complex phenotype of HGPS remains to be
      established. It has been shown that fibroblasts from HGPS patients are frequently
      resistant to immortalization with telomerase (hTERT), consistent with the idea
      that the loss of a dominant acting HGPS gene is a pre-requisite for
      immortalization. In this study we report the first detailed cytogenetic analysis
      of hTERT-immortalised HGPS cell lines from three patients and one corresponding
      primary fibroblast culture. Our results provide evidence for a cytogenetic
      mosaicism in HGPS with a distinctive pattern of chromosome aberrations in all the
      HGP clones. Chromosome 11 alterations were observed at a high frequency in each
      immortalised HGPS cell line but were also present at a lower frequency in the
      corresponding primary cells. Moreover, we were able to identify the 11q13-->q23
      region as a potential site of breakage. Our results are therefore consistent with
      a role of chromosome 11 alterations in the escape from senescence observed in
      HGPS cells. In addition to this defined rearrangement, we consistently observed
      complex chromosomal rearrangements, suggesting that HGPS displays features of
      chromosomal instability.

PMID- 16093718
TI  - FISH studies on the telomeric regions of the T-cell acute lymphoblastic leukemia
      cell line CCRF-CEM.
AB  - So far, the problem of an influence of translocations on the telomeres of the
      involved chromosomes has not been addressed yet in human cells. Therefore, the
      telomeres of a karyotypically rather well characterized T-cell acute
      lymphoblastic leukemia (T-ALL) cell line (CCRF-CEM) with several marker
      chromosomes were examined using peptide nucleic acid (PNA) telomere FISH probes
      to compare the telomere length of these markers with that of the chromosome arms
      of their origin. In addition, chromosome libraries, centromeric probes, and
      subtelomeric DNA probes were used to further define the marker chromosomes. Two
      markers could be newly defined and a concise karyotype of the cell line could be
      obtained by these detailed examinations: 42-47,X,-X,del(5)
      (q35?),t(5;15)(q14;q13.2),t(8;9)(p11;p24),del(9)(:p13-->qter)/inv(9)(pter-
      >p12::q21-->p12::q21-->qter),+13,+20,+der(22)(p+ [HSR?])[cp]. The relative
      telomere length of all chromosomes showed considerable interchromosomal,
      intercellular, and inter-passage variation. However, it could be shown, that in
      four different passages of the examined cell line the observed differences
      between relative telomere lengths of the markers and the chromosomes of their
      origin, with two exceptions (short arms of del/inv9 and der22), were not
      significant. On the other hand, because of its mentioned variability, telomere
      length alone is not sufficient to reliably define the derivation of markers.

PMID- 16093719
TI  - Radiosensitivity detected by the micronucleus test is not generally increased in
      sporadic prostate cancer patients.
AB  - The micronucleus test (MNT) has shown increased micronuclei (MN) frequencies in
      BRCA associated and sporadic breast cancer patients, Ataxia telangiectasia and
      Nijmegen Breakage Syndrome patients, demonstrating a common cellular phenotype of
      increased radiosensitivity. Some genes, causative of these diseases, have also
      recently been associated with prostate cancer. In order to investigate if
      prostate cancer exhibits the cellular phenotype of increased radiosensitivity, we
      performed MNT analysis on 22 sporadic prostate cancer patients and 43 male
      controls. We determined the baseline MN frequency, in order to see in vivo
      chromosomal damage without radiation, and induced (after irradiation with 2 Gy)
      frequency of MN, both in binucleated cells (BNC) obtained from cultured
      peripheral blood lymphocytes. An automated image analysis system was used to
      score the MN employing two different classifiers (Classifier A and B) for
      detection of BNC. The mean baseline frequencies were 48/43 MN/1000 BNC (A/B) for
      the controls and 42/50 (A/B) for prostate cancer patients. The induced MN
      frequencies amounted to 107/111 MN/1000 BNC (A/B) for controls and 111/114
      MN/1000 BNC (A/B) for prostate cancer patients. The obtained MN frequencies did
      not result in a statistically significant difference between unselected cases and
      controls. However, restricting the analysis to young patients (50-60 years, N =
      7) and age-matched controls (N = 7) revealed marginally significant higher MN
      frequencies in patients. We conclude that increased radiosensitivity is not a
      property of prostate cancer patients in general.

PMID- 16093720
TI  - Equine FISH mapping of 36 genes known to locate on human chromosome ends.
AB  - The INRA and the CHORI-241 horse BAC libraries were screened by hybridization
      with DNA probes and/or directly by PCR with primers designed in consensus
      sequences of genes localized at the end of each human chromosome. BAC clones were
      retrieved and 36 could be FISH mapped after the expected gene was confirmed in
      each BAC by sequencing. Our results show that 16 BACs can be considered to be at
      telomeric or centromeric positions in the horse and 15 were found at the boundary
      of actually defined conserved segments even-though often located within conserved
      syntenic fragments between horse and human. There is no straightforward relation
      between the end position of a marker in human and its end position in the horse.
      A gene was first anchored to ECA27 by FISH mapping. The localization of these
      markers expands the cytogenetic map of the horse and will serve as anchors for
      the integrated and future physical maps. It should also help to better understand
      the different chromosomal rearrangements that occurred during evolution of
      genomes derived from a common ancestral karyotype.

PMID- 16093721
TI  - Structure of equine 2'-5'oligoadenylate synthetase (OAS) gene family and FISH
      mapping of OAS genes to ECA8p15-->p14 and BTA17q24-->q25.
AB  - Mammalian 2'-5' oligoadenylate (2-5A) synthetases are important mediators of the
      antiviral activity of interferons. Both human and mouse 2-5A synthetase gene
      families encode four forms of enzymes: small, medium, large and ubiquitin-like.
      In this study, the structures of four equine OAS genes were determined using DNA
      sequences derived from fifteen cDNA and four BAC clones. Composition of the
      equine OAS gene family is more similar to that of the human OAS family than the
      mouse Oas family. Two OAS-containing bovine BAC clones were identified in
      GenBank. Both equine and bovine BAC clones were physically assigned by FISH to
      horse and cattle chromosomes, ECA8p15-->p14 and BTA17q24--> q25, respectively.
      The comparative mapping data confirm conservation of synteny between ungulates,
      humans and rodents.

PMID- 16093722
TI  - Differences in the pattern of X-linked gene expression between fetal bovine
      muscle and fibroblast cultures derived from the same muscle biopsies.
AB  - The sex determination system in mammals creates an imbalance between males and
      females in the number of X chromosomes. This imbalance is compensated through
      transcriptional silencing of one of the two X chromosomes in female diploid cells
      by epigenetic modifications. Although common for mammals, X inactivation shows
      marked species-specific differences in mechanisms and end results, and provides a
      unique opportunity to study epigenetic regulation of gene expression. The aim of
      the present study was to establish the expression pattern of selected X-linked
      genes in bovine fetal muscle tissue and muscle fibroblast cultures in order to
      follow possible modifications at the transcriptional level attributable to in
      vitro culture. We used heterologous cDNA microarray hybridization and
      quantitative real-time PCR to study the pattern of expression of X-linked genes
      including SLC25A6, GAB3, MECP2, RPS4X, JARID1C, UBE1, BIRC4 and SLC16A2.
      Quantitative real-time PCR analysis in fetal bovine muscle showed higher
      transcript levels in females for all X-linked genes tested with the exception of
      SLC25A6, with differences being significant for RPS4X, JARID1C and UBE1. The
      expression in fibroblast cultures derived from the same samples differed, with
      significantly higher levels for UBE1, GAB3 and BIRC4, while the rest of the panel
      of X-linked genes remained unchanged. The changed expression pattern in vitro,
      probably reflecting modifications in the epigenetic mechanisms that regulate
      transcriptional activity and gene silencing in X inactivation, has important
      implications for the advancement of new biotechnologies such as somatic cell
      nuclear transfer and stem cell therapy.

PMID- 16093723
TI  - Genomic structure and alternative transcript of bovine fatty acid synthase gene
      (FASN): comparative analysis of the FASN gene between monogastric and ruminant
      species.
AB  - Fatty acid synthesis differs considerably between monogastric and ruminant
      species. Fatty acid synthase (FASN) plays a central role in de novo lipogenesis
      in mammals. FASN has seven active sites which help to catalyse all the reaction
      steps in the conversion of acetyl-CoA and malonyl-CoA to palmitate. In this work,
      the bovine fatty acid synthase gene (FASN) was cloned, characterized and compared
      to the human and rat orthologs. Comparative analysis reveals evolutionarily
      conserved exon regions and gene flanking sequences. Analysis of the DNA sequence
      in the 5' flanking region of the FASN bovine gene revealed a potential TATA box,
      CAAT box and 5 Sp1 binding sites located in a CpG island. RT-PCR and Western blot
      analysis showed that FASN expression was higher in brain, testis and adipose
      tissue than in liver and heart. The longer form of the FASN cDNA includes a 7,542
      bp sequence which encodes a protein with 2,513 amino acids. An alternative
      transcript was discovered in bovine and ovine tissues devoid of part of exon 9.
      The removal of part of exon 9 by post-transcriptional splicing causes a
      frameshift in the open reading frame and results in a premature termination
      codon. We hypothesize that in ruminants, FASN may be regulated by the ratio
      between the two transcripts. The small transcript is mostly produced in tissues
      with low fatty acid synthesis.

PMID- 16093724
TI  - Molecular cloning, expression analysis and assignment of the porcine tumor
      necrosis factor superfamily member 10 gene (TNFSF10) to SSC13q34-->q36 by
      fluorescence in situ hybridization and radiation hybrid mapping.
AB  - We have cloned the complete coding region of the porcine TNFSF10 gene. The
      porcine TNFSF10 cDNA has an ORF of 870 nucleotides and shares 85% identity with
      human TNFSF10, and 75% and 72% identity with rat and mouse Tnfsf10 coding
      sequences, respectively. The deduced porcine TNFSF10 protein consists of 289
      amino acids with the calculated molecular mass of 33.5 kDa and a predicted pI of
      8.15. The amino acid sequence similarities correspond to 86, 72 and 70% when
      compared with human, rat and mouse sequences, respectively. Northern blot
      analysis detected TNFSF10-specific transcripts (approximately 1.7 kb) in various
      organs of a 10-week-old pig, suggesting ubiquitous expression. Real-time RT-PCR
      studies of various organs from fetal (days 73 and 98) and postnatal stages (two
      weeks, eight months) demonstrated developmental and tissue-specific regulation of
      TNFSF10 mRNA abundance. The chromosomal location of the porcine TNFSF10 gene was
      determined by FISH of a specific BAC clone to metaphase chromosomes. This TNFSF10
      BAC clone has been assigned to SSC13q34-->q36. Additionally, the localization of
      the TNFSF10 gene was verified by RH mapping on the porcine IMpRH panel.

PMID- 16093725
TI  - ESTs from brain and testis of White Leghorn and red junglefowl: annotation,
      bioinformatic classification of unknown transcripts and analysis of expression
      levels.
AB  - We report the generation, assembly and annotation of expressed sequence tags
      (ESTs) from four chicken cDNA libraries, constructed from brain and testis tissue
      dissected from red junglefowl and White Leghorn. 21,285 5'-end ESTs were
      generated and assembled into 2,813 contigs and 9,737 singletons, giving 12,549
      tentative unique transcripts. The transcripts were annotated using BLAST by
      matching to known chicken genes or to putative homologues in other species using
      the major gene/protein databases. The results for these similarity searches are
      available on www.sbc.su.se/~arve/chicken. 4,129 (32.9%) of the transcripts
      remained without a significant match to gene/protein databases, a proportion of
      unmatched transcripts similar to earlier non-mammalian EST studies. To estimate
      how many of these transcripts may represent novel genes, they were studied for
      the presence of coding sequence. It was shown that most of the unique chicken
      transcripts do not contain coding parts of genes, but it was estimated that at
      least 400 of the transcripts contain coding sequence, indicating that 3.2% of
      avian genes belong to previously unknown gene families. Further BLAST search
      against dbEST left 1,649 (13.1%) of the transcripts unmatched to any library. The
      number of completely unmatched transcripts containing coding sequence was
      estimated at 180, giving a measure of the number of putative novel chicken genes
      identified in this study. 84.3% of the identified transcripts were found only in
      testis tissue, which has been poorly studied in earlier chicken EST studies.
      Large differences in expression levels were found between the brain and testis
      libraries for a large number of transcripts, and among the 525 most frequently
      represented transcripts, there were at least 20 transcripts with significant
      difference in expression levels between red junglefowl and White Leghorn.

PMID- 16093726
TI  - Virus-like particle formation in Drosophila melanogaster germ cells suggests a
      complex translational regulation of the retrotransposon cycle and new mechanisms
      inhibiting transposition.
AB  - Transposition of 1731, a Drosophila melanogaster LTR retrotransposon, was
      investigated in reproductive organs by RNA, protein and VLP distribution during
      its life cycle. We detected 1731 transcription in oogonia but not in
      spermatogonia; in all cells during oogenesis but only in primary spermatocytes;
      and in ovarian cytoplasm but both in nuclei and cytoplasm of primary
      spermatocytes. By confocal scanning, we showed that whereas Gag protein appeared
      in all cytoplasms during oogenesis, in testes Gag detection began in late
      premeiotic primary spermatocytes and increased in elongating spermatids
      suggesting distinct mechanisms of 1731 transcription and translation regulation.
      By electron microscopy, we did not detect 1731 VLPs in ovaries, suggesting a
      complex post-translational control blocking VLP assembly and transposition.
      Interestingly, in testes we discovered VLP aggregates in cystic cytoplasm of
      maturing partially individualized spermatids. In testes, we observed two delays
      in 1731 product expressions, suggesting a complex temporal control mechanism.
      Transcriptional/translational delay may be determined by accumulation of 1731
      RNAs in primary spermatocyte nuclei. Translational/VLP assembly delay may be
      determined by post-transductional mechanisms controlling +1 frameshift and Pol
      protein degradation. Our results indicated two differential mechanisms inhibiting
      1731 transposition in Drosophila melanogaster ovaries and testes. In addition, we
      proposed a new mechanism for transposition control at the cell cycle level.

PMID- 16093727
TI  - Linkage disequilibrium inflates type I error rates in multipoint linkage analysis
      when parental genotypes are missing.
AB  - OBJECTIVES: Describe the inflation in nonparametric multipoint LOD scores due to
      inter-marker linkage disequilibrium (LD) across many markers with varied allele
      frequencies. METHOD: Using simulated two-generation families with and without
      parents, we conducted nonparametric multipoint linkage analysis with 2 to 10
      markers with minor allele frequencies (MAF) of 0.5 and 0.1. RESULTS:
      Misspecification of population haplotype frequencies by assuming linkage
      equilibrium caused inflated multipoint LOD scores due to inter-marker LD when
      parental genotypes were not included. Inflation increased as more markers in LD
      were included and decreased as markers in equilibrium were added. When marker
      allele frequencies were unequal, the r2 measure of LD was a better predictor of
      inflation than D'. CONCLUSION: This observation strongly supports the evaluation
      of LD in multipoint linkage analyses, and further suggests that unaccounted for
      LD may be suspected when two-point and multipoint linkage analyses show a marked
      disparity in regions with elevated r2 measures of LD. Given the increasing
      popularity of high-density genome-wide SNP screens, inter-marker LD should be a
      concern in future linkage studies.

PMID- 16093728
TI  - Inheritance of total serum IgE in the isolated Tangier Island population from
      Virginia: complexities associated with genealogical depth of pedigrees in
      segregation analyses.
AB  - OBJECTIVES: This study was aimed at performing a segregation analysis of total
      serum immunoglobulin E (tIgE) in an isolated population using maximal
      genealogical information permitted by current software and computer capacities,
      while assessing the reliability of the best-fitting model of inheritance for tIgE
      through simulations. METHODS: All current Tangier Island, VA, residents (n = 664)
      belonged to one large extended pedigree (n = 3,501) spanning 13 generations, with
      an average inbreeding coefficient of 0.009. Phenotype data were obtained on 453
      (68.2%) of the residents using a population-based recruitment scheme. Due to
      computational limitations resulting from the extremely complex pedigree
      structure, analysis on only two pedigree reconstructions was feasible: a reduced
      pedigree retaining all phenotyped individuals and their parents as 57 distinct
      families, and 922 nuclear families. RESULTS: Familial correlations and
      heritability calculations reveal a significant genetic component to tIgE in these
      data (heritability = 26%). The most parsimonious model to explain tIgE
      distribution indicated by the reduced pedigree structure was a two-distribution
      Mendelian model. However, larger and non-genetic models could not be rejected.
      Simulations over 200 replicates performed to evaluate the reliability of this
      model, indicated that using restricted genealogical information had minimal
      impact on results of segregation analyses performed here.

PMID- 16093729
TI  - Pharmacogenetics of oral anticoagulants.
AB  - The use of oral anticoagulants (OA) is problematic due to its association with
      hemorrhagic complications. OA metabolism relies on the CYP2C9 complex. Genetic
      variations compromising metabolic competence of this complex may explain the risk
      of excessive and hazardous anticoagulation. A pharmacogenetics-based approach to
      this issue could be beneficial for choosing adequate dose and duration of
      treatment, in addition to having a better understanding of pharmacological
      interactions to which OA are susceptible. However, evidence from several basic
      and clinical studies indicates that both a complicated system of regulation of
      expression of multiple genes and the influence of a wide variety of epigenetic
      factors could be responsible for adverse drug reactions associated with the use
      of OA. Emphasis on understanding the gene-environment interactions could attain
      new paths to facilitate the use of these important drugs in the quotidian
      clinical practice.

PMID- 16093730
TI  - Generation of tissue factor-rich microparticles in an ex vivo whole blood model.
AB  - The aim of this study was to investigate the role of blood cells in the
      expression of tissue factor (TF) and P-selectin in platelets and microparticles
      from blood stimulated with lipopolysaccharide (LPS), with or without the further
      addition of phorbol myristyl acetate (PMA). TF activity was found to be
      associated with platelets after 2 h incubation of whole blood with LPS or LPS +
      PMA, while no TF activity was detected in microparticles from blood subjected to
      such stimulation. In blood stimulated for 6 and 24 h, addition of PMA to the
      samples led to a substantial increase in TF activity associated with
      microparticles, compared with stimulation with LPS alone. Addition of PMA to
      blood samples also led to a three-fold increase in the amount of P-selectin found
      in the isolated microparticle fraction, and a 50% reduction in P-selectin
      measured in platelets, compared with LPS alone used for stimulation. In a
      different experiment, TF-rich microparticles were shown to be absorbed very
      efficiently by neutrophils in a calcium-independent reaction. Our results imply
      that LPS stimulation of whole blood is associated with a direct transfer of TF
      from monocytes to platelets in the absence of free TF-rich microparticles, which
      probably is accounted for by the fusion of TF-rich microparticles with activated
      platelets exposing P-selectin. Further addition of PMA to samples generates both
      free TF-rich microparticles as well as enhanced transfer of TF from monocytes to
      platelets.

PMID- 16093731
TI  - Demonstration of enhanced endogenous fibrinolysis in thrombin activatable
      fibrinolysis inhibitor-deficient mice.
AB  - To investigate the importance of thrombin activatable fibrinolysis inhibitor
      (TAFI) in the stabilization of plasma clots, we have compared fibrinolysis in
      TAFI-deficient (KO) and wild-type (WT) littermate mice. TAFI-deficient mice were
      previously generated by targeted gene disruption. The level of TAFI activity
      generated in plasma from WT mice in the presence of added thrombin and
      thrombomodulin (activatable TAFI) is twice that of plasma from TAFI heterozygous
      mice (HET); no activatable TAFI is detected in TAFI KO plasma. In vitro, TAFI KO
      plasma clots lysed faster than WT plasma clots, and HET plasma clots lysed at an
      intermediate rate. The rate of clot lysis for KO mice is not changed in the
      presence of potato carboxypeptidase inhibitor, a specific inhibitor of TAFIa,
      whereas the WT and HET clot lysis rates are increased in the presence of potato
      carboxypeptidase inhibitor. C-terminal lysine residues are preserved on partially
      degraded clots from KO mice, but are absent from partially degraded WT clots. In
      vivo, in a batroxobin-induced pulmonary embolism model, KO mice displayed a lower
      retention of fibrin in the lungs than did WT mice. These results are the first
      demonstration of enhanced endogenous fibrinolysis in an in vivo model without the
      addition of exogenous thrombolytic.

PMID- 16093732
TI  - Prevalence of factor V Leiden, prothrombin G20210A, and MTHFR G677A among 594
      thrombotic Jordanian patients.
AB  - Venous thromboembolism develops as the result of multiple interactions between
      non-genetic and genetic risk factors. In order to estimate the frequency of
      factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in Jordanian
      thrombotic patients, we studied 594 patients admitted to the King Hussein Medical
      Center for thrombophilia assessment. Polymerase chain reaction detected 25.7%
      (20.7% heterozygous, 5% homozygous), 6% (5.8% heterozygous, 0.2% homozygous) and
      31.7% (25% heterozygous, 6.7% homozygous) for factor V Leiden, prothrombin
      G20210A and MTHFR C677T mutations, respectively. A one-stage clotting assay was
      used to measure prothrombin activity. None of the prothrombin G20210A mutant
      patients had high prothrombin activity. The high prevalence found among our study
      group of factor V Leiden and prothrombin G20210A confirms the importance of
      thrombophilia screening for patients with venous thrombosis with family history
      and those with additional risk factors. On the contrary, the high prevalence of
      the MTHFR C677T mutation among arterial thrombosis patients shows its importance
      in screening in arterial thrombosis patients. These results, which are close to
      the prevalence found by other studies in the region, suggests that the Eastern
      Mediterranean region is probably the area of origin of these mutations,
      especially factor V Leiden. The knowledge of these frequencies in the Middle East
      region through population-based studies will contribute to a better understanding
      of the interaction between genetic and environmental risk factors underlying the
      mentioned mutations.

PMID- 16093733
TI  - 5-HT2A receptor antagonist increases circulating adiponectin in patients with
      type 2 diabetes.
AB  - We compared the levels of plasma adiponectin, platelet activation markers (P
      selectin, CD63, PAC-1, annexin V, and platelet-derived microparticles), and
      endothelial injury markers (soluble E-selectin and soluble vascular cell adhesion
      molecule-1) in 53 patients with type 2 diabetes mellitus to investigate potential
      contributions to diabetic vascular complications. In addition, we administered
      serotonin antagonist (sarpogrelate hydrochloride) to type 2 diabetes patients who
      had increased soluble E-selectin levels. The concentrations of platelet
      activation markers and endothelial injury markers in diabetic patients were
      significantly higher than those in normal subjects. However, levels of
      adiponectin were lower in type 2 diabetes patients than in control subjects. A
      total of 32 patients had high-soluble E-selectin levels (soluble E-selectin >or=
      62 ng/ml); a subset of patients that also had significant elevation of platelet
      activation and endothelial injury markers compared with patients without high
      soluble E-selectin. In addition, both platelet-P-selectin and platelet-derived
      microparticle levels negatively correlated with the adiponectin level. Patients
      with high soluble E-selectin exhibited significant improvement of all markers
      after sarpogrelate hydrochloride treatment. These findings suggest that there is
      a link between vascular change in type 2 diabetes and activated platelets,
      endothelial dysfunction, and an adiponectin abnormality.

PMID- 16093734
TI  - Clustering of haemostatic variables and the effect of high cashew and walnut
      diets on these variables in metabolic syndrome patients.
AB  - We investigated the effect of a high walnut and cashew diet on haemostatic
      variables in people with the metabolic syndrome. Factor analysis was used to
      determine how the haemostatic variables cluster with other components of the
      metabolic syndrome and multiple regression to determine possible predictors. This
      randomized, control, parallel, controlled-feeding trial included 68 subjects who
      complied with the Third National Cholesterol Education Program Expert Panel on
      Detection, Evaluation, and Treatment of High Blood Cholesterol criteria. After a
      3-week run-in following the control diet, subjects were divided into three groups
      receiving either walnuts or cashews (20 energy%) or a control diet for 8 weeks.
      The nut intervention had no significant effect on von Willebrand factor antigen,
      fibrinogen, factor VII coagulant activity, plasminogen activator inhibitor 1
      activity, tissue plasminogen activator activity or thrombin activatable
      fibrinolysis inhibitor. Statistically, fibrinogen clustered with the body-mass
      correlates and acute phase response factors, and factor VII coagulant activity
      clustered with high-density lipoprotein cholesterol (HDL-C). Tissue plasminogen
      activator activity, plasminogen activator inhibitor 1 activity and von Willebrand
      factor antigen clustered into a separate endothelial function factor. HDL-C and
      markers of obesity were the strongest predictors of the haemostatic variables. We
      conclude that high walnut and cashew diets did not influence haemostatic factors
      in this group of metabolic syndrome subjects. The HDL-C increase and weight loss
      may be the main focus of dietary intervention for the metabolic syndrome.
      Furthermore, diet composition may have only limited effects if weight loss is not
      achieved.

PMID- 16093735
TI  - The performance of quantitative D-dimer assays in laboratory routine.
AB  - Assessment of D-dimer in plasma is routinely used for the exclusion of venous
      thrombosis and the monitoring of hypercoagulability. Little information is
      available about the performance of D-dimer assays in clinical laboratories
      examined by external quality assessment schemes. We obtained results from 423
      laboratories measuring plasma pools from patients with elevated D-dimer levels
      mixed with human normal plasma. The results from five samples were reported
      containing D-dimer from the lower normal range up to a 20-fold increased level.
      In addition, information about the assignment of a cut-off point and the medical
      need to apply these assays was obtained by standardized questionnaire.
      Participants reported results and additional information from 20 different
      assays. Lack of standardization regarding the calibration concepts obstructs
      comparability of results. Results in one sample varied up to 20-fold between the
      assays applied. In addition, a high variability was reported around the cut-off
      values introduced for the exclusion of venous thrombosis and pulmonary embolism.
      As a consequence, generally accepted cut-off values cannot be established. For
      cut-off assignment, 62% of participants used the kit insert but also 14% used
      local validation. In conclusion, standardization or at least harmonization of D
      dimer assays is necessary to ensure comparability of D-dimer plasma levels
      measured in clinical routine.

PMID- 16093736
TI  - Short-course use of recombinant factor VIIa in a haemophilia patient with
      inhibitor undergoing cataract surgeries.
AB  - A 36 year-old patient with severe haemophilia A and high-titre inhibitor
      underwent cataract surgery under topical anaesthesia. Recombinant factor VIIa was
      used only three times, once before and twice following surgery. Tranexamic acid
      was given concomitantly. One month after the first successful procedure on the
      right eye, a second operation was performed on the left eye in the same manner.
      Both procedures were uneventful. Neither bleeding complications nor any other
      side effects occurred.

PMID- 16093737
TI  - Clotting time analysis of citrated blood samples is strongly affected by the tube
      used for blood sampling.
AB  - Our aim was to establish whether differences in clotting times for recalcified
      blood and plasma samples might be explained by the use of different blood
      collection tubes. Samples obtained from different plastic vacuum tubes were
      recalcified and clotting times determined by free oscillation rheometry. The
      clotting times for blood collected in Vacutainer (Becton Dickinson, Rutherford,
      New Jersey, USA) or Vacuette (Greiner Bio-One, Kremsmunster, Austria) tubes
      decreased with time, with maximal effect after 30 min. Blood from Monovette
      (Sarstedt, Numbrecht, Germany) tubes displayed longer clotting times, which did
      not decrease with time. Clotting times for plasma prepared after 1 h storage in
      Vacutainer or Vacuette tubes were unaffected by subsequent addition of corn
      trypsin inhibitor to inhibit factor XIIa, although an antibody against factor XI
      prolonged the clotting time markedly. In Monovette plasma, both corn trypsin
      inhibitor and anti-factor XI effectively prolonged the clotting time. When corn
      trypsin inhibitor or anti-factor XI was added to the tubes before blood
      collection, but both additions clearly prolonged the clotting times in all types
      of tubes, even though corn trypsin inhibitor was less effective in whole blood.
      Antibodies against human tissue factor did not affect the clotting times. The
      amounts of platelet or leukocyte microparticles in plasma were low and similar in
      all tubes. This indicates that blood collection in Vacutainer or Vacuette tubes
      induces a rapid activation of factor XII and factor XI.

PMID- 16093738
TI  - Short-term venous stasis influences routine coagulation testing.
AB  - Preanalytical variability is a common source of errors in coagulation testing, as
      clotting assays are particularly susceptible to poor standardization of the whole
      analytical process. To investigate the effect of a short-term venous stasis on
      routine coagulation testing, we measured activated partial thromboplastin time,
      prothrombin time, fibrinogen and D-dimer in plasma specimens collected either
      without venous stasis or following the application of a 60 mmHg constant,
      standardized external pressure by a sphygmomanometer, for 1 (1-min stasis) and 3
      min (3-min stasis). When compared with blood specimens collected without stasis,
      the Pearson's correlation coefficients and the corresponding slopes of the
      Passing and Bablok regression line of samples collected following 1 and 3-min
      stasis were acceptable. However, statistically significant differences by paired
      Student's t-test could be observed for all parameters tests following 3-min
      stasis, and for all but the activated partial thromboplastin time after 1-min
      stasis. Significant difference between specimens collected after 1- and 3-min
      stasis was also achieved for prothrombin time (P < 0.01), fibrinogen (P < 0.01)
      and D-dimer (P < 0.05). The agreement between measurements was yet acceptable
      after 1-min stasis, but achieved clinical significance for prothrombin time,
      fibrinogen and D-dimer after 3-min stasis. Taken together, results of the present
      investigation confirm that the effects of venous stasis during venipuncture are
      clinically meaningful. As hematocrit values and activities of clotting factors
      VII, VIII and XII significantly increased, whereas that of activated factor VII
      remained unchanged, we hypothesize that a short-term venous stasis, as induced by
      up to 3-min tourniquet placing, might not be sufficient to produce additional
      procoagulant responses besides hemoconcentration.

PMID- 16093739
TI  - Mild factor VII deficiency due to heterozygosis is not associated with a bleeding
      tendency.

PMID- 16093741
TI  - Childhood abuse and pain in adulthood: more than a modest relationship?

PMID- 16093742
TI  - Documented and self-reported child abuse and adult pain in a community sample.
AB  - OBJECTIVES: To examine the association of chronic pain in young adults with
      childhood exposure to maltreatment and to determine whether depressive symptoms
      mediate such an association. DESIGN: A total of 649 members of a randomly
      selected cohort of young adults from a multiwave, multi-informant epidemiological
      study were interviewed with regard to chronic pain and symptoms of major
      depressive disorder. Maltreatment was measured both by retrospective self-report
      and by official records of substantiated child maltreatment. OUTCOME MEASURES:
      Current complaints of frequent pain and functionally impairing chronic pain were
      assessed in young adult interviews at mean age 22. RESULTS: Net of demographic
      factors, adult chronic pain was associated with self-reported sexual abuse. This
      association persisted after the contribution of concurrent depression was
      statistically controlled. Elevations of pain attributable to documented
      maltreatment were comparatively modest and below the threshold of statistical
      significance. Pain complaints in participants who self-reported physical abuse
      were not significantly elevated. CONCLUSIONS: Overall, results show an
      association between self-reported sexual abuse history and adult pain complaints
      in this general population sample, which was not attributable to symptoms of
      depression at the time of such reports.

PMID- 16093743
TI  - Sexual and physical abuse in women with fibromyalgia syndrome: a test of the
      trauma hypothesis.
AB  - OBJECTIVES: According to the trauma hypothesis, women with fibromyalgia syndrome
      (FMS) are more likely to report a history of sexual and/or physical abuse than
      women without FMS. In this study, we rely on a community sample to test this
      hypothesis and the related prediction that women with FMS are more likely to have
      posttraumatic stress disorder than women without FMS. METHODS: Eligibility for
      the present study was limited to an existing community sample in which FMS and
      major depressive disorder were prevalent. The unique composition of the original
      sample allowed us to recruit women with and without FMS from the community. A
      total of 52 female participants were enrolled in the present FMS group and 53 in
      the control (no FMS) group. Sexual and physical abuse were assessed
      retrospectively using a standardized telephone interview. RESULTS: Except for
      rape, sexual and physical abuse were reported equally often by women in the FMS
      and control groups. Women who reported rape were 3.1 times more likely to have
      FMS than women who did not report rape (P<0.05). There was no evidence of
      increased childhood abuse in the FMS group. Women with FMS were more likely to
      have posttraumatic stress disorder symptoms (intrusive thoughts and arousal) as
      well as posttraumatic stress disorder diagnosis (P<0.01). DISCUSSION: With the
      exception of rape, no self-reported sexual or physical abuse event was associated
      with FMS in this community sample. In accord with the trauma hypothesis, however,
      posttraumatic stress disorder was more prevalent in the FMS group. Chronic stress
      in the form of posttraumatic stress disorder but not major depressive disorder
      may mediate the relationship between rape and FMS.

PMID- 16093744
TI  - Is self-reported childhood abuse history associated with pain perception among
      healthy young women and men?
AB  - OBJECTIVE: A self-reported history of childhood physical and/or sexual abuse is
      frequently reported among chronic pain populations and has been associated with
      poorer adjustment to pain. In addition, self-reported abuse history has been
      related to increased pain complaints in population-based studies. One possible
      explanation for the association between abuse and clinical pain is that abuse
      victims may display enhanced sensitivity to painful stimuli, which increases the
      risk of developing clinical pain. However, the limited evidence addressing this
      issue has been mixed. The purpose of this study was to examine the association
      between self-reported history of childhood sexual or physical abuse and
      experimental pain responses in a nonclinical sample of generally healthy young
      adults. DESIGN: Participants were 110 (56 female, 54 male) college students who
      completed a series of questionnaires assessing abuse history, recent pain, health
      care utilization, perceived health, and psychologic variables. Also, measures of
      thermal and ischemic pain threshold and tolerance were obtained in all
      participants. In addition, a procedure assessing temporal summation of heat pain
      was conducted in which intensity and unpleasantness ratings of repetitive thermal
      stimuli were obtained. Systolic and diastolic blood pressure and heart rate were
      assessed at resting and during the ischemic pain task. RESULTS: Participants with
      a positive childhood abuse history were oversampled, yielding 21 out of 56
      (37.5%) women with a positive history of abuse and 13 out of 54 (24.1%) PHA men.
      No abuse group differences emerged for thermal or ischemic pain thresholds or
      tolerances (P values>0.05). However, compared to women with no childhood abuse
      history, women with a positive history of abuse provided significantly lower
      average pain unpleasantness and peak pain unpleasantness ratings and lower
      unpleasantness ratings of the first trial during the temporal summation
      procedure, whereas no abuse group differences emerged for men. Also, compared to
      participants with no childhood abuse history, participants of both genders with a
      positive history of abuse demonstrated smaller increases (ie, less temporal
      summation) in pain unpleasantness ratings across trials of thermal stimulation,
      and participants with a positive history of abuse showed greater decreases in
      pain intensity and unpleasantness after reaching their peak pain level (ie,
      greater wind-down) compared to participants with no childhood abuse history. In
      addition, participants with a positive history of abuse reported more sites of
      recent pain, poorer perceived health, greater somatization, and more negative
      affect. No group differences in resting cardiovascular measures or cardiovascular
      reactivity were observed. CONCLUSION: These findings indicate that a self
      reported history of childhood abuse is associated with decreased sensitivity to
      experimentally induced pain, especially among women. However, abuse history was
      associated with increased pain complaints, poorer self-reported health, and
      greater negative affect. These data highlight the complexity of the relationship
      between abuse history and pain and illustrate the need for further investigation
      of potential pain-related correlates of abuse.

PMID- 16093745
TI  - Are reports of childhood abuse related to the experience of chronic pain in
      adulthood? A meta-analytic review of the literature.
AB  - BACKGROUND: Recent empirical evidence suggests that childhood abuse may be
      related to the experience of chronic pain in adulthood. To date, a systematic
      quantitative review of the literature has not been presented. OBJECTIVES: The
      purpose of this study was to use meta-analytic procedures to evaluate the
      strength of existing evidence of the association between self-reports of
      childhood abuse and the experience of chronic pain in adulthood. METHODS:
      Analyses were designed to test the relationship across several relevant criteria
      with 4 separate meta-analyses. RESULTS: Results of the analyses are as follows:
      1) individuals who reported being abused or neglected in childhood also reported
      more pain symptoms and related conditions than those not abused or neglected in
      childhood; 2) patients with chronic pain were more likely to report having been
      abused or neglected in childhood than healthy controls; 3) patients with chronic
      pain were more likely to report having been abused or neglected in childhood than
      nonpatients with chronic pain identified from the community; and 4) individuals
      from the community reporting pain were more likely to report having been abused
      or neglected than individuals from the community not reporting pain. CONCLUSION:
      Results provide evidence that individuals who report abusive or neglectful
      childhood experiences are at increased risk of experiencing chronic pain in
      adulthood relative to individuals not reporting abuse or neglect in childhood.

PMID- 16093746
TI  - A comparison of physician and nonphysician acupuncture treatment for chronic low
      back pain.
AB  - BACKGROUND: Although up to a third of the 10,000 acupuncturists in the United
      States are medical doctors, little is known about the acupuncture techniques they
      use or how their practices compare with those of nonphysician licensed
      acupuncturists. This is the first study providing descriptive data on physician
      acupuncture and comparison to nonphysician acupuncture. PURPOSE: This study
      describes how a random sample of physician acupuncturists in the United States
      diagnose and treat chronic low back pain and contrasts their practices with those
      of nonphysician licensed acupuncturists. METHODS: A total of 464 questionnaires
      were mailed to physician acupuncturists randomly sampled from 3 sources: web
      based Yellow Pages, American Academy of Medical Acupuncturists (AAMA) membership,
      and Pain Clinics associated with American College of Graduate Medical Education
      approved fellowship programs. Responses (n=137, 30%) were analyzed using
      descriptive statistics. The results of this survey were compared with data
      published from a similar survey of nonphysician licensed acupuncturists in
      Washington State. RESULTS: Physicians who perform acupuncture use a mixture of
      styles and emphasize neuroanatomic approaches to needle placement. Most
      physicians received training in French Energetic acupuncture. In contrast, most
      nonphysician licensed acupuncturists use a traditional Chinese medicine approach
      to needle placement. Despite this apparent difference in their predominant styles
      of acupuncture, there was a high correlation between physician and nonphysician
      licensed acupuncturist acupoint selection to treat low back pain. In addition to
      acupuncture needling, physicians use other medical treatments, whereas
      nonphysician licensed acupuncturists' employ a variety of traditional Chinese
      medicine adjuncts to needling. CONCLUSION: This study provides new information
      about the nature of physician acupuncture practice in the United States and how
      it compares to acupuncture provided by nonphysician licensed acupuncturists.
      Further research is necessary to determine if the different types of acupuncture
      provided by physicians and nonphysician acupuncturists affect treatment outcomes
      and costs for patients with chronic low back pain.

PMID- 16093748
TI  - How pain and analgesics disturb sleep.
AB  - OBJECTIVE: Clinical experiences as well as specific investigations show that pain
      and sleep disturbances are closely correlated. The aims of this review are first
      to describe sleep disturbances related to painful medical diseases and analgesics
      and secondly to propose management possibilities for these sleep disturbances.
      METHOD: The viewpoints presented were based mainly on objective rest activity and
      sleep studies using actigraphy and polysomnography. RESULTS: Polysomnographic and
      actigraphic studies have described significant sleep disturbances in patients
      suffering from different pain disorders. These disturbances are: reduced sleep
      efficiency and altered sleep architecture characterized by increased wakefulness
      and stage 1 non-rapid eye movement sleep, associated with diminished slow wave
      sleep and rapid eye movement sleep. Sleep disturbances may be related to pain and
      to the analgesic or sedative medications administered. CONCLUSION: If many
      factors, including pain, disease process per se, as well as medication, could
      disturb sleep, sleep disturbances may also adversely affect the natural course of
      the painful disease. Improving sleep quantity and quality in patients with
      painful disorders may break this vicious circle and as consequence enhance the
      patients' overall health and quality of life.

PMID- 16093747
TI  - The responses to pharmacological challenges and experimental pain in patients
      with chronic whiplash-associated pain.
AB  - OBJECTIVES: This study evaluates the analgesic responses to intravenous
      administration of morphine, lidocaine, and ketamine and their relations to
      duration of chronic pain after whiplash trauma. In addition, experimental muscle
      pain sensitivity and its correlation to pain duration and pharmacological
      responses were assessed. METHODS: Thirty-three patients with diagnosed whiplash
      associated disorder grade II in the chronic stage, according to the Quebec
      classification, were included. The pharmacological evaluation was performed in a
      randomized, double-blind, cross-over design and consisted of a 30-minute period
      of intravenous administration of morphine (0.3 mg/kg), lidocaine (5 mg/kg),
      ketamine (0.3 mg/kg), or placebo (isotonic saline). Intensity ratings of habitual
      pain on a visual analogue scale were taken before, during, and after the
      infusion. The patients were classified as nonresponders, placebo-responders, or
      responders (minimum 50% decrease of pain intensity) of the drugs. Pressure pain
      thresholds and intramuscular and cutaneous electrical stimulation pain thresholds
      were measured. The pain intensity during experimental muscle pain by
      intramuscular hypertonic saline was also recorded. Experimental pain assessments
      were performed on the lower legs outside the habitual painful area. RESULTS:
      Thirty patients completed the study; 2 were placebo responders and 10 were
      nonresponders. Of 18 responders, there were 15 morphine responders, 11 lidocaine
      responders, and 14 ketamine responders. In the patients with whiplash-associated
      disorder duration less than 2 years, 7 responded to morphine, 5 to lidocaine, and
      8 to ketamine. In the patients with pain duration longer than 2 years, 8
      responded to morphine, 6 to lidocaine, and 6 to ketamine. Thus, no pattern with
      respect to pain duration was found. Seventeen patients participated in the
      experimental pain assessment, and no significant differences in the variables of
      the intramuscular and cutaneous stimulation and intramuscular-induced pain with
      respect to response to the pharmacological challenges or whiplash-associated
      disorder duration existed. DISCUSSION: The pharmacological challenges identified
      subgroups of patients with chronic whiplash-associated disorder that might be
      considered before instituting therapeutic interventions or research. However, the
      pattern of responses to the pharmacological challenges did not show any clear
      relationships with pain duration or the experimental pain tests.

PMID- 16093749
TI  - Psychological, behavioral, and family characteristics of pediatric patients with
      chronic pain: a 1-year retrospective study and cluster analysis.
AB  - OBJECTIVES: There has been a longstanding recognition that adult patients with
      chronic pain are not a homogenous population and that there are subgroups of
      patients who report high levels of distress and interpersonal difficulties as
      well as subgroups of patients who report little distress and high functioning.
      The purpose of the present study was to attempt to identify similar subgroups in
      a pediatric chronic pain population. METHODS: The sample consisted of 117
      children with chronic pain and their parents who were assessed in a
      multidisciplinary pain clinic during 2001. Participants completed a set of
      psychologic self-report questionnaires, as well as demographic and pain
      characteristic information. A cluster analysis was conducted to identify 3
      distinct subgroups of patients to replicate similar studies of adult chronic pain
      sufferers. RESULTS: Overall, mean scores were within population norms on measures
      of distress and family functioning, with somatic symptoms at a level of clinical
      significance. The cluster analysis identified the 3 subgroups that were
      strikingly similar to those identified in adult chronic pain populations: one
      with high levels of distress and disability, another with relatively low scores
      on distress and disability, and a third group that scored in between the other 2
      on these measures but with marked low family cohesion. DISCUSSION: The similarity
      of these subgroups to the adult chronic pain population subgroups as well as
      implications for future studies are discussed.

PMID- 16093750
TI  - The roles of pain catastrophizing and anxiety in the prediction of postoperative
      pain intensity: a prospective study.
AB  - OBJECTIVES: This study was a prospective investigation of the extent to which
      psychologic variables could be predictive of postoperative pain. Study aims were:
      1) to evaluate whether an assessment of pre-operative distress factors could
      predict the intensity of postoperative pain; and 2) to characterize the unique
      pattern in which anxiety and pain catastrophizing scores relate to postoperative
      pain. METHODS: The Pain Catastrophizing Scale and the State-Trait Anxiety
      Inventory were administered to 38 patients scheduled for elective abdominal
      surgery. The questionnaires were completed on the day of admission, a day before
      the operation. On day 1 and day 2 following the operation, perception of pain
      intensity at the surgical wound was assessed by visual analog scale. RESULTS: The
      Pain Catastrophizing Scale and State-Trait Anxiety Inventory scores were
      significantly correlated with the postoperative pain scores. A linear regression
      analysis showed that Pain Catastrophizing Scale predicted the level of
      postoperative pain intensity even after controlling for state anxiety and that
      trait anxiety was not a significant predictor. In addition, analysis of the
      unique pattern of each predictor related to postoperative pain intensity
      indicated a linear curve for the Pain Catastrophizing Scale and curvilinear curve
      for the state anxiety. DISCUSSION: The results are discussed in light of
      appraisal and coping theories. It is suggested that a simple assessment of
      preoperative catastrophizing tendency and anxiety scores may assist medical teams
      in postoperative pain management.

PMID- 16093751
TI  - Sacroiliac joint dysfunction: evaluation and management.
AB  - Sacroiliac joint dysfunction is believed to be a significant source of low back
      and posterior pelvic pain. METHODS: To assess the clinical presentation,
      diagnostic testing, and treatment options for sacroiliac joint dysfunction, a
      systematic literature review was performed using MEDLINE. RESULTS: Presently,
      there are no widely accepted guidelines in the literature for the diagnosis and
      treatment of sacroiliac instability. Establishing management guidelines for this
      disorder has been complicated by the large spectrum of different etiologic
      factors, the variability of patient history and clinical symptoms, limited
      availability of objective testing, and incomplete understanding of the
      biomechanics of the sacroiliac joint. CONCLUSIONS: A reliable examination
      technique to identify the sacroiliac joint as a source of low back pain seems to
      be pain relief following a radiologically guided injection of a local anaesthetic
      into the sacroiliac joint. Most patients respond to non-operative treatment.
      Patients who do not respond to non-operative treatment should be considered for
      operative sacroiliac joint stabilization.

PMID- 16093752
TI  - The value and validity of single-needle approach for multiple medial branch
      blocks is not proven.

PMID- 16093754
TI  - The role of myocardial perfusion imaging in the diagnosis of patients with
      coronary artery disease: developments over the past year.
AB  - PURPOSE OF REVIEW: The role of myocardial perfusion imaging in the diagnosis of
      coronary artery disease in various patient populations has been expanding. Recent
      literature from March 2004 to February 2005 has advanced the concept of
      attenuation correction and electrocardiographic gating in improving the diagnosis
      of coronary artery disease. RECENT DEVELOPMENTS: The American Heart Association
      encourages the use of electrocardiographic-gated single photon emission
      computerized tomography in women. Asymptomatic diabetic patients may benefit from
      screening with myocardial perfusion imaging. Dobutamine stress perfusion imaging
      is an important diagnostic tool in elderly patients who are unable to exercise.
      In patients with chest pain, acute imaging may decrease unnecessary admissions.
      Vasodilator stress imaging has high sensitivity and specificity in patients with
      left bundle branch block. Patients undergoing endovascular stent grafting may
      benefit from risk stratification with vasodilator myocardial perfusion imaging.
      The American Society of Nuclear Cardiology and the Society of Nuclear Medicine
      have recognized the role of attenuation correction in increasing the diagnostic
      accuracy of myocardial perfusion imaging. Multiple studies emphasize the
      importance of electrocardiographic gating in myocardial perfusion imaging.
      SUMMARY: Recent developments have resulted in an important statement by the
      American Heart Association that assigns a larger role for myocardial perfusion
      imaging in the diagnosis of coronary artery disease in women. The role of
      myocardial perfusion imaging is also expanding in various other patient
      populations. The literature has validated the concept of attenuation correction
      for the accurate assessment of attenuation artifacts as well as
      electrocardiographic gating in enhancing the diagnosis and risk stratification
      for coronary artery disease.

PMID- 16093755
TI  - Diagnostic and prognostic value of coronary artery calcium screening.
AB  - PURPOSE OF REVIEW: Algorithms and equations to calculate risk of cardiovascular
      events, though very useful as an in-office tool to conduct a preliminary
      assessment demonstrate a limited ability to predict risk in the individual
      patient. This has favored the development of several imaging modalities for
      subclinical atherosclerosis such as imaging of coronary calcium by computed
      tomography. RECENT FINDINGS: Arterial wall calcification is intimately associated
      with atherosclerosis development and is therefore an optimal marker of the
      presence of disease. The paradigm underlying the use of imaging technologies to
      identify subclinical disease is that the quantification of plaque burden may
      provide a better risk stratification approach for the individual patient than the
      currently available tools. SUMMARY: The most recent evidence supports this
      approach as will be discussed in the current review.

PMID- 16093756
TI  - Intravenous myocardial contrast echocardiography for the diagnosis of coronary
      artery disease.
AB  - PURPOSE OF REVIEW: Myocardial contrast echocardiography is a recently developed
      technique that permits the noninvasive assessment of myocardial perfusion.
      Myocardial contrast enhancement from microbubbles characteristically reflects the
      myocardial blood volume. The analysis of microbubble kinetics using quantitative
      myocardial contrast echocardiography permits the evaluation of myocardial blood
      flow both at rest and during pharmacological stress. RECENT FINDINGS: Myocardial
      contrast echocardiography has been shown to have good concordance with single
      photon emission computed tomography for the localization of perfusion
      abnormalities. As a result of its better spatial resolution and the fact that it
      tracks myocardial blood flow changes, it seems to have higher sensitivity for the
      detection of angiographically significant coronary artery disease, while
      maintaining similar specificity to single photon emission computed tomography.
      Low mechanical index imaging techniques (real-time myocardial contrast
      echocardiography) have the advantage of permitting simultaneous analysis of wall
      motion and perfusion, which is particularly important during dobutamine stress.
      Myocardial perfusion analysis using real-time myocardial contrast
      echocardiography has been shown to have higher sensitivity and diagnostic
      accuracy than wall motion analysis for the detection of coronary artery disease.
      Quantitative myocardial contrast echocardiography seems to overcome the expertise
      requirements for appropriate interpretation of myocardial perfusion images, and
      may have been demonstrated to be an accurate supplemental technique for
      estimating the severity of coronary artery disease. SUMMARY: Recent technological
      advances have positioned myocardial contrast echocardiography as a safe and
      feasible technique for the evaluation of myocardial perfusion. The analysis of
      myocardial perfusion using myocardial contrast echocardiography has higher
      diagnostic accuracy than wall motion analysis for detecting coronary artery
      disease.

PMID- 16093757
TI  - The use of stress echocardiography for prognostication in coronary artery
      disease: an overview.
AB  - PURPOSE OF REVIEW: Stress echocardiography has a high accuracy for the detection
      of coronary artery disease. Additionally, it provides clinically useful
      prognostic information, such as resting left ventricular function, myocardial
      viability, stress-induced ischemia, vascular extent of wall motion abnormalities,
      and changes in end-systolic volume and ejection fraction with stress. RECENT
      DEVELOPMENTS: The timing, extent, and severity of the stress-induced wall motion
      abnormalities are important determinants of long-term prognosis. Previous studies
      have shown the efficacy of stress echocardiography in predicting long-term
      cardiac events in mixed patient groups and the value of this test in selected
      patient subsets. SUMMARY: This review attempts to define the role of stress
      echocardiography for prognostication in coronary artery disease, pointing out the
      ability of this technique to identify low-risk and high-risk subsets among
      patients with known or suspected coronary artery disease and thus guide patient
      management decisions.

PMID- 16093758
TI  - Stress echocardiography for the diagnosis of coronary artery disease: progress
      towards quantification.
AB  - PURPOSE OF REVIEW: This review highlights recent progress in the quantitative
      approach to the interpretation of stress echocardiograms. Recent literature
      regarding the application of tissue Doppler and strain rate imaging for the
      diagnosis of coronary artery disease is summarized. RECENT FINDINGS: The high
      temporal and spatial resolution of tissue Doppler and strain rate imaging permit
      recognition of regional myocardial dysfunction. These techniques have been
      performed during low- and high-dose dobutamine stress echocardiography and have
      been applied to exercise echocardiography. During stress, the peak systolic
      velocity and early diastolic velocity increased to a greater degree in normal
      segments compared to ischemic segments. With tissue Doppler imaging, viable
      segments show increases in systolic velocities in contrast to infarcted segments.
      Presently, the feasibility of strain rate imaging is slightly less than that of
      conventional wall motion assessment. However, in preliminary studies, tissue
      Doppler parameters and especially strain rate parameters appear to offer
      advantages in accuracy compared to conventional wall motion assessment. SUMMARY:
      Tissue Doppler and strain rate imaging offer great promise for the accurate,
      reproducible quantification of regional myocardial function. Further studies are
      indicated to prove their accuracy, efficiency, and superiority over existing
      methods.

PMID- 16093759
TI  - Molecular pathology of aging and its implications for senescent coronary
      atherosclerosis.
AB  - PURPOSE OF REVIEW: This review highlights common mechanisms of organismal aging
      and inflammatory coronary atherosclerosis. RECENT FINDINGS: A substantial body of
      evidence now indicates that aging is largely due to molecular damage inflicted by
      reactive oxygen species, electrophiles, and other reactive endobiotic and
      xenobiotic metabolites. Our understanding of genetic pathways regulating
      longevity began 12 years ago with the discovery that a developmental-arrest
      program in the nematode Caenorhabditis elegans also has marked effects on adult
      lifespan. This pathway, closely related to the insulin and insulinlike growth
      factor-signaling pathways of mammals, modulates longevity and stress resistance
      in several model organisms. Insulin-like signaling also has an impact on redox
      signaling, antioxidant defenses, and metabolic generation of oxidative stress.
      Recently, additional signaling pathways--involving Sirtuins, AMP kinase, Jun N
      terminal kinase 1, and other master regulatory proteins--have been implicated in
      longevity and stress-resistance mechanisms. The inflammatory process involves
      acute production of reactive oxygen species by specialized cells responding to
      infection, exposure to toxins or allergens, cell damage, hypoxia,
      ischemia/reperfusion, and other factors, initiating signaling through several of
      these pathways. Free radical chain reactions arise from lipid oxidation and
      generate oxidized low-density lipoprotein, a powerful inflammatory signal and
      potentiator of atherosclerosis. Oxidized low-density lipoprotein accumulates in
      atherosclerotic arteries, particularly in rupture-prone regions. Inflammation
      involving oxidative stress, by way of the production of reactive oxygen species,
      is a hallmark of coronary atherosclerosis. SUMMARY: Common pathways underlie both
      organismal aging and tissue-autonomous senescent pathologic processes, such as
      coronary atherosclerosis. The mechanisms discovered in model organisms may lead
      to pharmacotherapeutic interventions.

PMID- 16093760
TI  - C-reactive protein and cardiovascular disease: a critical appraisal.
AB  - PURPOSE OF REVIEW: C-reactive protein, a nonspecific marker of inflammation, has
      recently been proposed both as a marker of low-grade inflammation involved in
      atherogenesis and as a predictor of disease progression. RECENT FINDINGS: The
      physiologic functions of C-reactive protein as an anti-inflammatory scavenger
      molecule have begun to emerge. For example, C-reactive protein binds to damaged
      lipoproteins and facilitates their removal by phagocytes without full complement
      activation. Increased levels of C-reactive protein may result in direct effects
      on vascular cells, including induction of cytokines and prothrombotic factors.
      Several sources of biologic variation in the levels of C-reactive protein have
      been identified, chief among which are abdominal obesity and the metabolic
      syndrome. Although previous studies showed a potent independent association of C
      reactive protein levels with cardiac events, the strength of association was
      shown to be much weaker than previously reported in recent large meta-analyses.
      Therapy with nonspecific anti-inflammatory agents such as statins in patients
      with coronary artery disease has been found to reduce adverse outcomes in
      association with reductions in C-reactive protein, on the basis of retrospective
      analysis of stored blood specimens. SUMMARY: Despite a relatively strong
      epidemiologic association with future adverse cardiovascular events, the great
      majority of apparently healthy individuals with elevated C-reactive protein will
      not experience cardiovascular disease. Even though more than 15 000 articles in
      PubMed mention C-reactive protein, current knowledge is insufficient to implicate
      C-reactive protein as a causative factor in atherothrombosis or to enable the
      recommendation of C-reactive protein testing to guide preventive or therapeutic
      interventions in cardiovascular diseases.

PMID- 16093761
TI  - Prevention of atrial fibrillation.
AB  - PURPOSE OF REVIEW: This review summarizes current concepts on the pathophysiology
      of atrial fibrillation, identifying predisposing factors to guide primary and
      secondary preventive approaches. RECENT FINDINGS: Many factors contribute to the
      development and progression of atrial fibrillation, including cardiovascular
      diseases, age, neurohormones, genetics, diet, autonomic influences, and
      inflammation. Therapeutic efforts have been directed to modify this altered
      milieu and prevent the development of atrial electrical and structural
      remodeling. This nonconventional antiarrhythmic management appears to have an
      important role also in secondary prevention of atrial fibrillation; the
      indications for conventional antiarrhythmic agents are decreasing because of side
      effects and limited efficacy. Interventional electrophysiology techniques have
      been developed to target the arrhythmia substrate responsible for the initiation
      or maintenance of atrial fibrillation, achieving high success rates. SUMMARY:
      Atrial fibrillation is the most commonly treated arrhythmia and its incidence is
      predicted to increase. It is associated with significant morbidity and mortality.
      Preventive efforts should be initiated early and include diversified
      interventions to correct predisposing factors and modify the altered atrial
      substrate.

PMID- 16093762
TI  - Sodium directly impairs target organ function in hypertension.
AB  - PURPOSE OF REVIEW: A large body of epidemiologic evidence has been amassed
      attesting to the relation of increased salt ingestion to the prevalence of
      hypertension; however, only a minority of patients with essential hypertension
      are salt sensitive. This report discusses the hypothesis that salt sensitivity
      need not be demonstrated exclusively by a marked rise in arterial pressure with
      salt loading; it may also be manifested by evidence of impaired target organ
      structure and function. RECENT DEVELOPMENTS: This discussion summarizes the
      authors' recent experience with the spontaneously hypertensive rat, the best
      experimental model for naturally occurring hypertension, which demonstrates that
      salt loading precipitates the common structural and functional cardiac and renal
      changes associated with long-standing hypertension. SUMMARY: As a result of salt
      loading, left ventricular diastolic dysfunction and impaired renal excretory
      function with massive proteinuria occur. Both are associated with marked ischemia
      and fibrosis and only a small additional increase in arterial pressure.

PMID- 16093763
TI  - Guidelines on cardiovascular disease prevention in clinical practice: the
      European perspective.
AB  - PURPOSE OF REVIEW: To summarize the recommendations of the Third Joint European
      Society's Task Force on Cardiovascular Disease Prevention in Clinical Practice so
      that these may be made accessible to a wider audience. RECENT FINDINGS: The
      relative importance of population and high-risk strategies for cardiovascular
      disease prevention is summarized. The guidelines stress the primacy of total risk
      assessment to guide management decisions. The hazards of decisions based on
      assessment of single risk factors is illustrated. Compared with earlier
      guidelines, the focus has changed from coronary heart disease to total
      cardiovascular disease prevention. A new system for predicting total
      cardiovascular disease mortality risk (Systematic Coronary Risk Evaluation) is
      presented. Explicit clinical priorities are defined. SUMMARY: Total
      cardiovascular risk should be assessed before making management decisions.
      Individuals with established cardiovascular disease and those with high total
      cardiovascular risk gain most from preventive advice. This high-risk approach
      should be complemented by a population-based preventive strategy.

PMID- 16093764
TI  - Bibliography. Current world literature. Imaging and echocardiography.

PMID- 16093766
TI  - Neurohormonal control of exocrine pancreatic secretion.
AB  - PURPOSE OF REVIEW: Investigations into the neural and hormonal control of
      pancreatic exocrine function have led to many exciting discoveries over the past
      year. This review seeks to identify those articles that further our understanding
      into the complex relation of the varying factors regulating pancreatic secretion.
      RECENT FINDINGS: Major findings include the new insights into the regulation of
      the pancreas through receptor-mediated mechanisms, investigations of pancreatic
      exocytosis, impairment of pancreatic exocrine function by insulin deficiency, the
      effects of surgical interventions for the treatment of chronic pancreatitis on
      pancreatic exocrine function, how exocrine function is altered by the cause of
      acute pancreatitis, and clinical observations relating to management of
      pancreatic disease and investigations of pancreatic function testing. SUMMARY:
      Over the past year, substantial new information has been published on the
      neurohormonal control of pancreatic exocrine function. These data provide
      insights into the physiology and pathophysiology of pancreatic secretion and
      diseases of exocrine insufficiency.

PMID- 16093767
TI  - Acute pancreatitis.
AB  - PURPOSE OF REVIEW: This review presents advances in our understanding of the
      pathobiologic responses that mediate acute pancreatitis with an emphasis on the
      interrelationship between the events occurring in the pancreatic acinar cell and
      the vascular, neural, and immune systems; information on recent reports
      describing clinical diagnostic and therapeutic aspects of autoimmune
      pancreatitis; and information on feeding strategies during acute pancreatitis.
      RECENT FINDINGS: The reports during the past year provide important and
      clinically relevant findings about roles of intracellular events as well as
      vascular and neural regulatory pathways involved in the mechanism of
      pancreatitis. Reports during the past year also add to our rapidly growing
      portfolio describing the characteristics, course, and therapeutic responses in
      autoimmune pancreatitis. Finally, a provocative report demonstrates that a low
      fat elemental-like diet administered by nasogastric tube during severe
      pancreatitis does not worsen outcome compared with administration of the diet by
      nasojejunal tube. This report provides rationale for early feeding in these
      patients by a simpler route than previously recommended and also raises the
      question about the types of nutrients that should be used in this situation that
      have the least effect on neurohumoral stimulation of the pancreas. SUMMARY: Our
      understanding of the mechanistic processes that mediate the pathobiologic
      responses of pancreatitis is rapidly evolving. The continuing challenge is to
      translate these findings into treatment strategies for pancreatitis.

PMID- 16093768
TI  - Chronic pancreatitis.
AB  - PURPOSE OF REVIEW: As in our previous reviews, we endeavor to review important
      new observations in chronic pancreatitis made in the past year. We included
      articles, including review articles, only if they contained new observations or
      readdressed old questions and provided new insights into old and new concepts.
      RECENT FINDINGS: Important observations include the following: (1) Strong
      association between cystic fibrosis transmembrane regulator dysfunction/mutations
      and 'recurrent acute pancreatitis', particularly in patients with pancreas
      divisum (2) Pancreas divisum may be incidental finding in recurrent acute
      pancreatitis (3) Smoking increases risk of chronic pancreatitis (4) Coxsackie B
      virus may increase severity of alcoholic chronic pancreatitis (5) CD4+ T cells
      and an immune reaction against amylase may play a role in pathogenesis of
      autoimmune pancreatitis (6) 2-(18F)-Fluro-2-deoxy-D-glucose positron emission
      tomography might be useful to detect pancreatic cancer in chronic pancreatitis
      patients at risk for developing pancreatic cancer, but contrast-enhanced Doppler
      ultrasound or endosonography may be as sensitive and better than contrast
      enhanced computed tomography (7) Superiority of surgery vs endotherapy for long
      term pain relief and weight gain in painful chronic pancreatitis (8) Early
      treatment of pain and malabsorption may improve life quality (9) Antifibrogenesis
      and fibrolytic agents as potential therapies. SUMMARY: Ongoing basic and clinical
      research this past year has further characterized genetic, molecular and clinical
      aspects of chronic pancreatitis. The advent of predictable and lasting treatments
      of chronic pancreatitis is most likely to appear on the wings of carefully
      conducted studies targeting genetic and molecular mechanisms of chronic
      pancreatitis, particularly pancreatic fibrogenesis.

PMID- 16093769
TI  - When developmental signaling pathways go wrong and their impact on pancreatic
      cancer development.
AB  - PURPOSE OF REVIEW: To describe recent studies of developmental signal pathways
      and their relation to the development of pancreatic cancer. RECENT FINDINGS:
      Pancreatic development and its relation to pancreatic cancer remain one of the
      most provocative areas in the field of pancreatology. Interestingly, for a long
      time, investigators in this field of research worked diligently in describing
      pathways that were shared by both processes, hoping that the day would come when
      their efforts would be translated into the development of diagnostic modalities
      and new treatments. Fortunately, during the past 2 years, we have witnessed the
      development of small molecules that specifically target distinct pathways, thus
      providing the proof of principle that the hope of many scientists in the field of
      pancreatic cancer was justified. SUMMARY: This conceptual validation of previous
      experiments has fuelled new studies, the results of which will be the focus of
      this review.

PMID- 16093770
TI  - New advances in pancreatic imaging.
AB  - PURPOSE OF REVIEW: Exciting new developments and applications of imaging
      techniques in pancreatic diseases have emerged. This review discusses these new
      advances and how they are improving our ability to diagnose malignancies and
      inflammatory lesions, to grade severity of pancreatitis, and to stage pancreatic
      cancer accurately. RECENT FINDINGS: A new computed tomography severity index
      shows promise for grading the severity of acute pancreatitis. Magnetic resonance
      imaging is comparable with computed tomography in staging acute pancreatitis.
      Analysis of pancreatograms and textural changes of the parenchyma may prove
      helpful in diagnosing chronic pancreatitis. Contrast enhanced ultrasonography may
      prove to be a useful way to judge the degree of inflammation and fibrosis in
      autoimmune pancreatitis and to monitor response to steroid therapy. The debate
      over the best means of staging pancreatic cancer has focused on endoscopic
      ultrasound and computed tomography. Preliminary studies with contrast enhanced
      ultrasonography report improved diagnostic and staging capabilities with
      pancreatic cystic and solid neoplasms. Improvements in positron emission
      tomography/computed tomography scans may improve the detection of neuroendocrine
      tumors. SUMMARY: These new advances will help refine the diagnosis and staging of
      pancreatic diseases.

PMID- 16093771
TI  - Pancreatic surgery.
AB  - PURPOSE OF REVIEW: This is a review and summary of pertinent publications that
      have affected the surgical management of pancreatic disease in 2004. RECENT
      FINDINGS: The surgical treatment of pancreatic cancer continues to advance. Over
      the past year, there have been several reports of collected experiences with
      pancreaticoduodenectomy. Most patients with pancreatic cancer do not have
      resectable disease, and the recent thoughts on palliation are discussed. Three
      institutions published large series on the treatment of intraductal pancreatic
      mucinous neoplasms. Laparoscopic surgery is being used more widely to manage
      islet cell tumors of the pancreas and chronic pancreatitis. The complications of
      acute and chronic pancreatitis continue to be serious concerns for clinicians.
      SUMMARY: The surgical management of pancreatic diseases continues to evolve as
      surgical techniques and our knowledge of the disease processes improve. A renewed
      clinical and scientific focus on this organ is changing the treatment of
      pancreatic neoplasms and holds the promise of improved outcomes.

PMID- 16093772
TI  - Double-balloon endoscopy.
AB  - PURPOSE OF REVIEW: Our strategy for small intestinal diseases has dramatically
      been brushed up with a novel technique, double-balloon endoscopy, which exhibits
      extremely better insertability and maneuverability compared with conventional
      methods. Double-balloon endoscopy has a potential to change radically the
      approach for the small intestinal diseases in the future. In this article, the
      publications on double-balloon endoscope will be reviewed. RECENT FINDINGS: A
      double-balloon endoscope can be inserted into deeper portions of the small
      intestine via both oral and anal approaches, and allows endoscopic observation as
      well as treatment for the entire small intestine without general anesthesia.
      Reports have been made on this method's safety and low frequency of complication:
      it is very useful for diagnosis and treatment of small intestinal diseases,
      including small intestinal bleeding, small intestinal tumor, stenosis of small
      intestine, and polyposis syndrome. SUMMARY: The development of double-balloon
      endoscopy enabled observation and treatment in the entire small intestine. The
      double-balloon endoscopy has a potential to be a standard of enteroscopy by
      replacing conventional push enteroscopy and intraoperative enteroscopy. In the
      near future, the double-balloon endoscopy, together with the capsule endoscopy,
      will be essential modalities for the management of small intestinal diseases.

PMID- 16093773
TI  - Endoscopic confocal microscopy.
AB  - PURPOSE OF REVIEW: Endoscopic confocal microscopy is a new endoscopic imaging
      technology that produces high-magnification cross-sectional images of the
      gastrointestinal epithelium during endoscopy. These high-magnification images
      might allow the endoscopist to make a tissue diagnosis during endoscopy without
      biopsy and histopathology. The purpose of this article is to review the salient
      features of endoscopic confocal microscopy, describe current clinical research
      areas using the technology, and depict its potential role in the management of
      gastrointestinal diseases. This review includes an overview of the technology, a
      review of recent publications describing its function, and a discussion of
      potential applications. RECENT FINDINGS: Endoscopic confocal microscopy has been
      technologically feasible only for a short time; therefore, the published
      experience is limited. Studies describing the use of endoscopic confocal
      microscopy for the detection of dysplastic tissue have been limited to a single
      paper in which endoscopic confocal microscopy was reported to be highly sensitive
      and specific for the detection of colonic dysplasia in a general screening
      population. Active areas of investigation include detecting dysplasia in
      ulcerative colitis and Barrett's esophagus. A recent case report detailed the
      ability of endoscopic confocal microscopy to detect gastric Helicobacter pylori
      in vivo. SUMMARY: Endoscopic confocal microscopy is a new imaging technology that
      produces high-magnification cross-sectional images of the gastrointestinal tract.
      Its role in detecting and managing diseases of the gastrointestinal tract has
      been studied in colon cancer screening and is currently being evaluated in a
      variety of premalignant conditions.

PMID- 16093774
TI  - Colonoscopic surveillance in inflammatory bowel disease.
AB  - PURPOSE OF REVIEW: To describe recent findings in the literature aimed at
      decreasing systematic error in dysplasia surveillance in inflammatory bowel
      disease. RECENT FINDINGS: Despite great promise, colonoscopic surveillance in
      inflammatory bowel disease has yet to be demonstrated to reduce colorectal cancer
      mortality. In part, this stems from a number of inherent systematic troubles,
      including low rates of observer agreement among pathologists; lack of consensus
      on the natural history of dysplasia, particularly low-grade dysplasia; the patchy
      nature of dysplasia, which leads to sampling error caused by insufficient biopsy
      by endoscopists; and incomplete patient follow-up. Recent publications that have
      focused on defining better the natural history of different levels of dysplasia
      and improving dysplasia identification at the time of colonoscopy may aid in
      overcoming the flaws of surveillance. The key recent findings include conflicting
      evidence on the relative danger of flat low-grade dysplasia, the safety of
      treating polypoid low-grade dysplasia as a benign adenoma in the absence of flat
      dysplasia in the rest of the colon or the surrounding mucosa, and preliminary
      support of chromoendoscopy to target dysplasia better during colonoscopy and to
      limit unnecessary nontargeted biopsies. SUMMARY: These and other advances stand a
      reasonable chance of making surveillance a more accurate tool to discriminate
      between patients with chronic colitis likely to progress to advanced pathology
      and those less likely to do so. Such advances may result in effective
      surveillance in which both colorectal cancer mortality and unnecessary colectomy
      may be limited.

PMID- 16093775
TI  - Endoscopy in celiac disease.
AB  - PURPOSE OF REVIEW: The primary objective of this review is to highlight the
      evidence for the role of endoscopy in celiac disease. RECENT FINDINGS: Evidence
      is presented that the endoscopic markers of celiac disease are specific although
      not sensitive for the disease. Villous atrophy, the hallmark of celiac disease,
      is patchy in the duodenum, and various techniques may identify areas of villous
      atrophy. These methods include magnification endoscopy and chromoendoscopy. The
      most recent innovation, video capsule endoscopy, may be of value in the diagnosis
      of celiac disease and in the assessment of patients with complicated celiac
      disease. SUMMARY: Endoscopy and duodenal biopsies are the mainstay for diagnosing
      celiac disease. Although characteristic endoscopic features may be useful, their
      absence does not exclude celiac disease. Random biopsy, even of normal-appearing
      mucosa is necessary for the diagnosis of celiac disease.

PMID- 16093776
TI  - Endoscopic approaches to the treatment of gastroesophageal reflux disease.
AB  - PURPOSE OF REVIEW: Endoscopic therapies for gastroesophageal reflux disease
      represent a minimally invasive alternative to medical or surgical treatment.
      These devices include suturing, radiofrequency energy, and bulking agent
      technologies. Research into the use of these technologies in gastroesophageal
      reflux disease continues to accelerate, and the last 2 years have witnessed
      significant developments that may affect current and future clinical practice.
      RECENT FINDINGS: Long-term data from nonrandomized clinical trials have become
      available in the last 2 years for many gastroesophageal reflux disease
      endotherapies, providing some insight into their durability. Furthermore, two
      multicenter and one single-center sham-controlled trials were published recently,
      allowing comparison between groups. SUMMARY: Although it is premature to propose
      the superiority of any individual approach, emerging data in this rapidly
      evolving field may inform current and future directions in the research and
      treatment of gastroesophageal reflux disease.

PMID- 16093777
TI  - Endoscopic palliation of pancreatic adenocarcinoma.
AB  - PURPOSE OF REVIEW: Endoscopic therapies have become an indispensable modality in
      the treatment and palliation of complications from pancreatic adenocarcinoma.
      This review focuses on treatment of biliary obstruction, malignant gastric outlet
      obstruction, and intractable abdominal pain resulting from unresectable
      pancreatic adenocarcinoma. Novel and emerging endoscopic approaches are also
      briefly discussed. RECENT FINDINGS: Endoscopic placement of a biliary stent is
      the modality of choice for palliation of biliary obstruction. Biliary self
      expanding metal stents should be placed if expected survival is more than 6
      months and plastic stents if expected survival is less than 6 months. For
      endoscopic palliation of gastric outlet obstruction, enteral self-expanding metal
      stents should be placed. Biliary self-expanding metal stents should be considered
      prior to the placement of a duodenal stent. Palliation of intractable abdominal
      pain can safely be performed with endoscopic ultrasound-guided celiac plexus
      neurolysis using bupivacaine and absolute alcohol. Exciting novel endoscopic
      approaches are being evaluated especially in the area of drug-eluted biliary
      stents, endoscopic creations of enteral anastomoses, and endoscopic ultrasound
      guided injection of gene vectors. SUMMARY: The frontier of endoscopic palliative
      therapies for pancreatic adenocarcinoma is expanding. Clinical trials are needed
      to evaluate novel endoscopic approaches.

PMID- 16093778
TI  - Current world literature. Pancreas.

PMID- 16093780
TI  - Immunotherapy for thrombotic thrombocytopenic purpura.
AB  - PURPOSE OF REVIEW: This review focuses on recent advances in the use of immune
      based therapy to treat patients with refractory and relapsing acquired thrombotic
      thrombocytopenic purpura. RECENT FINDINGS: Advances in understanding of the
      pathophysiology of idiopathic thrombotic thrombocytopenic purpura have provided
      the rationale for immune-based treatment approaches to refractory and relapsing
      cases of thrombotic thrombocytopenic purpura. The demonstration that a severe
      deficiency of von Willebrand factor-cleaving protease activity in acquired
      thrombotic thrombocytopenic purpura is due to an autoantibody inhibitor of the
      von Willebrand factor-cleaving protease argues for targeting the antibody
      inhibitor of the von Willebrand factor-cleaving protease with immunosuppressive
      therapy as a means of increasing protease activity and inducing a sustained
      remission of the disease. Recent publications, largely case reports and small
      series of patients, have suggested a role for rituximab and cyclosporine in cases
      refractory to plasma exchange or resistant to the tapering of plasma exchange
      therapy. SUMMARY: In the future, a better understanding of the relation between
      the von Willebrand factor-cleaving protease activity, the nature and titer of von
      Willebrand factor-cleaving protease inhibitors, and the risk of relapse of
      thrombotic thrombocytopenic purpura will be important to further validate the
      strategy of targeting the von Willebrand factor-cleaving protease inhibitory
      antibody as an effective means of treating acquired thrombotic thrombocytopenic
      purpura. Prospective data from carefully designed clinical trials are needed to
      define the effectiveness of specific immunosuppressive therapies at suppressing
      antibody inhibitors of von Willebrand factor-cleaving protease, improving von
      Willebrand factor-cleaving protease activity, and inducing a sustained remission
      of the disease.

PMID- 16093781
TI  - Racial disparities in risk factors for thrombosis.
AB  - PURPOSE OF REVIEW: Until recently, the paucity of characterization of the
      epidemiology of venous thromboembolism among non-Caucasians has contributed to
      the misconception that race or ethnicity does not modify disease presentation.
      This review will describe the previously poorly documented magnitude of venous
      thromboembolism disease burden among four racial cohorts, by defining disease
      incidence and associated morbidity/mortality from available literature data.
      RECENT FINDINGS: Emerging data suggest that African-Americans possess the highest
      burden of venous thromboembolism, and Asians the lowest, compared with the
      Caucasian population. In both racial groups, however, the inheritable
      thrombophilic risk factors prevalent in Caucasians (factor V Leiden, Prothrombin
      G20210A) are distinctly rare. The presence of yet undetermined modifiers of
      disease, conferring susceptibility or resistance to venous thromboembolism among
      these racial groups, is suspected and requires further investigation. SUMMARY:
      Racial disparity in thrombotic disorders exists in the divergent patterns of
      disease incidence among different racial/ethnic cohorts, yet the genetic
      determinants of disease and modifiers of risk remain obscure. Further research
      focused on delineating the underlying etiologies of venous thromboembolism across
      different racial/ethnic groups promises to be a productive and much needed area
      of exploration.

PMID- 16093782
TI  - Long-term outcomes of venous thrombosis in children.
AB  - PURPOSE OF REVIEW: Venous thromboembolism has become an increasingly recognized
      clinical entity in children over the past decade. Recently, important efforts
      have been made to track post thrombotic outcomes. The present review discusses
      the knowledge gained from seminal studies in the field over the past decade, with
      particular emphasis on the findings of numerous published reports on outcomes of
      various types of venous thromboembolism in the pediatric literature from January
      2003 to January 2005. RECENT FINDINGS: Large cohort studies involving acute
      venous thromboembolism of all types in children have recently confirmed a rather
      low frequency of recurrent venous thromboembolism, but have shown a lack of
      thrombus resolution following standard-duration anticoagulant therapy in as many
      as 50% of patients. In addition, the development of the post thrombotic syndrome
      has been demonstrated in greater than one third of children with venous
      thromboembolism involving the extremities. Persistent thrombosis despite adequate
      anticoagulation has been independently associated with complete vaso-occlusion at
      diagnosis. Furthermore, the presence of elevated levels of factor VIII and D
      dimer either at diagnosis or following three to six months anticoagulation has
      now been defined as a predictor of adverse long-term outcomes of pediatric
      thrombosis. SUMMARY: This body of work indicates that the various forms of venous
      thromboembolism in children are in general associated with a considerable degree
      of adverse outcomes, particularly in the form of venous thromboembolism-related
      mortality, recurrent thromboembolism, and development of post thrombotic
      syndrome. Advances in the prediction of post thrombotic outcomes have begun, and
      must continue to facilitate a risk-stratified approach to antithrombotic
      management in children, and to ultimately achieve meaningful improvements in long
      term outcomes.

PMID- 16093783
TI  - Fibrinogen heterogeneity: inherited and noninherited.
AB  - PURPOSE OF REVIEW: Many noninherited or inherited variations have been described
      in fibrinogen and they may affect the different functions of fibrinogen. RECENT
      FINDINGS: A number of the acquired variations in fibrinogen affect the properties
      of the fibrinogen molecule, such as the conversion rate to fibrin and/or the
      characteristics of the fibrin clot. Also, genetic polymorphisms are known that
      can affect the function of the fibrinogen molecule. In addition, some other
      genetic variants are associated with plasma levels of fibrinogen and with the
      increase of fibrinogen levels during an acute-phase reaction. SUMMARY: In this
      review the authors discuss the noninherited and inherited variations of
      fibrinogen and the clinical implications (e.g. when determining the risk of
      cardiovascular disease).

PMID- 16093784
TI  - Measurement of ADAMTS13 activity and inhibitors.
AB  - PURPOSE OF REVIEW: Acquired or congenital deficiency in the plasma von Willebrand
      factor-cleaving protease ADAMTS13 causes life-threatening thrombotic
      thrombocytopenic purpura. This condition is characterized primarily by
      thrombocytopenia and microangiopathic hemolytic anemia, accompanied by variable
      degrees of neurologic dysfunction, renal failure, and fever. Measurement of
      ADAMTS13 activity is important in the diagnosis of microangiopathies such as
      thrombotic thrombocytopenic purpura. This review introduces both established and
      emerging assays for ADAMTS13 activity, focusing on their impact on clinical
      practice. RECENT FINDINGS: Previously established assays are useful screening
      methods to identify suspected thrombotic thrombocytopenic purpura. Novel assays
      measuring ADAMTS13 activity using either recombinant peptides or synthetic
      substrates directly measure the activity quantitatively. These assays can also
      detect neutralizing autoantibodies in the plasma of patients with acquired
      ADAMTS13 deficiency. Although ADAMTS13 in control subjects exhibits a broad
      variation in activity, ranging from 30 to 200%, significant decreases in ADAMTS13
      activity have been observed in several physiologic and pathologic conditions. A
      portion of thrombotic thrombocytopenic purpura patients, however, did not display
      severe ADAMTS13 deficiency, suggesting that as-yet-unidentified environmental or
      genetic factors may contribute to the etiology of thrombotic thrombocytopenic
      purpura. SUMMARY: New assays measuring ADAMTS13 activity will contribute
      significantly to the accurate diagnosis of microangiopathies, ultimately leading
      to improved clinical treatment of these diseases. These assays may also help to
      clarify the role of ADAMTS13 activity in additional thrombotic disorders,
      including disseminated intravascular coagulation, stroke, and myocardial
      infarction.

PMID- 16093785
TI  - Management and prevention of recurrent hemarthrosis in patients with hemophilia.
AB  - PURPOSE OF REVIEW: Degenerative arthropathy resulting from recurrent hemarthrosis
      remains the largest source of noninfectious morbidity for persons with
      hemophilia. Optimal treatment to prevent or reduce joint destruction remains
      controversial. RECENT FINDINGS: The most exciting developments in the past year
      have contributed to our understanding of the pathophysiology behind this
      destructive process. Particularly interesting is the possible role of
      protooncogenes and angiogenic factors in the development of hypertrophic
      synovitis. Arthroscopic synovectomy effectively controls the hypertrophic
      synovium and resultant bleeding, and can be used safely even in very young
      patients. Prophylactic factor replacement remains the mainstay to reduce or
      prevent joint damage. New approaches, chiefly dose escalation strategies, have
      shown promise instead of standard prophylactic regimens. Additionally aggressive
      on-demand approaches may be feasible. These techniques allow for fewer indwelling
      venous access devices in small children, as rates of complications with these
      devices are shown to be increasingly high. Whether prophylactic therapy can be
      safely stopped in certain patients is an evolving area of interest. Outcome
      measures are being validated to assess the impact of interventions on patient
      quality of life. SUMMARY: As hemophilia care evolves, current on-demand and
      prophylactic regimens will be optimized. Synovectomy will likely play a larger
      role in the control of synovitis, and validated quality-of-life scores will allow
      more consistent communication of outcomes. New understanding of the molecular
      mechanisms of joint destruction will pave the way for new therapeutic options for
      persons with hemophilia.

PMID- 16093786
TI  - Hormone replacement therapy and risk for venous thromboembolism: what's new and
      how do these findings influence clinical practice?
AB  - PURPOSE OF REVIEW: Although an association between hormone replacement therapy
      and venous thromboembolism has been established, several unanswered questions
      remain. This review will address additional questions relating to hormone
      replacement therapy and venous thromboembolism. Does the risk for venous
      thromboembolism differ according to the type of hormone replacement therapy? Does
      the presence of thrombophilia influence the risk for venous thromboembolism in
      hormone replacement therapy users? Should hormone replacement therapy be
      temporarily interrupted around the time of surgery? RECENT FINDINGS: The risk for
      venous thromboembolism seems to be less in users of estrogen-only hormone
      replacement therapy (odds ratio = 1.2; 95% confidence interval: 0.6-2.6) than in
      users of estrogen-progestin hormone replacement therapy (odds ratio = 2.7; 95%
      confidence interval: 1.4-5.1), and there may be no increased risk for venous
      thromboembolism with transdermal hormone replacement therapy (odds ratio = 1.0;
      95% confidence interval: 0.3-3.3). The presence of a prothrombotic blood
      abnormality, such as the factor V Leiden mutation, seems to further increase the
      risk for venous thromboembolism in hormone replacement therapy users (odds ratio
      = 17.1; 95% confidence interval: 3.7-78). Continued use of hormone replacement
      therapy in the perioperative period does not seem to have an impact on the
      overall risk for postoperative venous thromboembolism (odds ratio = 0.66; 95%
      confidence interval: 0.35-1.18). SUMMARY: Recent studies have extended our
      understanding regarding the association between hormone replacement therapy and
      venous thromboembolism. The implications of these findings on clinical practice
      are discussed.

PMID- 16093787
TI  - Intracellular signaling in platelets.
AB  - PURPOSE OF REVIEW: Over the past few years, a large portion of platelet research
      has focused on intracellular signaling events that contribute to stable platelet
      adhesion and aggregation. RECENT FINDINGS: Studies of knockout mice have
      suggested critical roles for several previously unappreciated signaling molecules
      including phosphatidylinositol 3-kinase, the exchange factor CalDAG-GEFI, and the
      small GTPase Rap1b. These proteins may function to remodel the platelet
      cytoskeleton and thereby regulate both adhesion and aggregation. The abundant
      cytoskeletal protein talin appears to be a key regulator of the platelet integrin
      alphaIIbbeta3. Recent evidence suggests that talin binding to the cytoplasmic
      tail of beta3 promotes integrin oligomerization, thereby increasing the binding
      avidity the alphaIIbbeta3 complex for fibrinogen. SUMMARY: The identification of
      platelet signaling pathways not only has clinical implications for diagnosis, but
      perhaps more importantly for rationale drug design. Aspirin, dipyridamole
      (Persantine), and thienopyridines (ticlopidine and clopidogrel) are all examples
      of agents that specifically target discrete platelet signaling pathways. These
      drugs have already been proven to be beneficial in the treatment of
      cardiovascular disease. Novel agents that target newly identified signaling
      pathways hold promise of greater specificity and efficacy.

PMID- 16093788
TI  - Bibliography current world literature.

PMID- 16093790
TI  - Biology and therapy of mantle cell lymphoma.
AB  - PURPOSE OF REVIEW: Mantle cell lymphoma is an aggressive non-Hodgkin's lymphoma
      characterized by the t(11;14) chromosomal translocation and overexpression of
      cyclin D1. Constituting approximately 5 to 8% of all non-Hodgkin's lymphomas, it
      carries the poorest prognosis among non-Hodgkin's lymphoma subtypes. Standard and
      effective treatment approaches have yet to be established. RECENT FINDINGS:
      Several recent insights regarding the molecular pathogenesis and prognostic
      biomarkers have been realized by way of comparative genomic hybridization, cDNA
      microarray, and proteomic analysis. Clinical trials using chemotherapy plus
      rituximab have shown improved response rates, including complete remissions, but
      without cure in most cases, indicating a clear need for new treatment approaches.
      Novel therapies for relapsed disease using the proteasome inhibitor bortezomib,
      thalidomide plus rituximab, the cyclin inhibitor flavopiridol, or inhibitors of
      the mammalian target of rapamycin (mTOR) have shown encouraging clinical
      responses. Stem cell transplantation, including nonmyeloablative approaches, are
      being incorporated into therapeutic regimens and show promise in both the front
      line and relapsed/refractory settings. SUMMARY: This review summarizes recent
      advances in the biology, pathogenesis, and therapy of mantle cell lymphoma and
      identifies ongoing areas of clinical investigation and new treatment approaches.

PMID- 16093791
TI  - Current status of therapeutic vaccines for non-Hodgkin's lymphoma.
AB  - PURPOSE OF REVIEW: Therapeutic vaccines targeting B cell lymphoma idiotype have
      reached an advanced stage of clinical development, with three multicenter
      randomized clinical trials ongoing. This review describes the rationale and
      development of this immunotherapeutic approach, the design of current phase III
      trials, and other active vaccination approaches likely to move forward into
      clinical testing for lymphomas. RECENT FINDINGS: Several groups have achieved
      promising results in phase II trials of patient-specific idiotype vaccines, with
      very few side effects noted. Anti-idiotype antibodies, in addition to cytotoxic T
      cells, are now believed to be important effectors of antitumor immunity after
      idiotype vaccination. The manufacturing of autologous tumor idiotype proteins is
      being rapidly refined by the use of molecular technologies. Two trials involving
      more than 1000 patients are now under way, which use idiotype vaccination after
      induction chemotherapy; one trial completed accrual in early 2004. A third trial
      opened in 2004, using rituximab followed by idiotype vaccine with maintenance
      booster vaccines continuing throughout the period of normal B cell recovery. In
      accordance with the United States Food and Drug Administration, progression-free
      survival serves as the accepted primary efficacy endpoint in these studies.
      SUMMARY: Lymphoma idiotype vaccination represents a promising immunotherapeutic
      approach targeting a patient-specific tumor antigen. The results of pivotal phase
      III trials for three first-generation idiotype vaccines will become available in
      the next several years. Advanced manufacturing techniques should permit
      application of this tailor-made treatment to large numbers of non-Hodgkin's
      lymphoma patients.

PMID- 16093792
TI  - Positron emission tomography imaging for lymphoma.
AB  - PURPOSE OF REVIEW: To review the current role and the limitations of F
      fluorodeoxygenase positron emission tomography in the management of lymphoma,
      with a particular focus on studies published since January 2004. RECENT FINDINGS:
      F-fluorodeoxygenase positron emission tomography should be routinely performed at
      the initial diagnosis of patients with suffering from Hodgkin's disease because
      it adds useful informations to conventional staging techniques. Residual F
      fluorodeoxygenase uptake is an important prognostic factor after one or a few
      cycles of chemotherapy, but it is clearly too early to change patient treatment
      on the basis of F-fluorodeoxygenase positron emission tomography results. F
      fluorodeoxygenase positron emission tomography is the best noninvasive imaging
      technique after treatment; however, it is always indicated to correlate positron
      emission tomography findings with clinical data, other imaging modalities, a
      biopsy, or all three to reduce the risk of false positive results. There are some
      concerns about the positive predictive value of positron emission tomography
      after treatment, especially in childhood lymphoma. Clinicians should be aware of
      positron emission tomography findings in specific clinical conditions in this
      patient population. F-fluorodeoxygenase positron emission tomography combined
      with computed tomography offers advantages over the two used separately and read
      side by side. It may be particularly useful for the planning of radiation therapy
      or for the planning of a surgical biopsy. Several studies have shown that F
      fluorodeoxygenase positron emission tomography is definitively superior to Ga
      scintigraphy. New radiotracers such as F-fluorothymidine may be useful for the
      noninvasive assessment of proliferation in vivo. SUMMARY: F-fluorodeoxygenase
      positron emission tomography has become the most important nuclear medicine
      imaging modality in the field of lymphoma. It should be routinely used in the
      treatment of lymphoma patients.

PMID- 16093793
TI  - Cancer in AIDS.

PMID- 16093794
TI  - Targeting human herpesvirus-8 for treatment of Kaposi's sarcoma and primary
      effusion lymphoma.
AB  - PURPOSE OF REVIEW: Human herpesvirus-8, also called the Kaposi's sarcoma
      herpesvirus, is present in all cases of Kaposi's sarcoma and primary effusion
      lymphoma and in some cases of multicentric Castleman's disease. This review
      discusses mechanisms by which human herpesvirus-8 contributes to tumorigenesis
      and how this knowledge can be used to target the virus for the treatment of these
      tumors. RECENT FINDINGS: Most primary effusion lymphomas and Kaposi's sarcoma
      tumor cells are latently infected with human herpesvirus-8 and hence resistant to
      antiherpesvirus drugs that are dependent on lytic replication. In contrast, many
      of the cells infected with human herpesvirus-8 in multicentric Castleman's
      disease support lytic replication, so that clinical improvement frequently occurs
      in response to treatment with antiherpesvirus drugs. The resistance of latently
      infected tumor cells to antiherpesvirus drugs can be overcome by inducing human
      herpesvirus-8 to reenter the lytic cascade in the presence of antiherpesvirus
      drugs. This leads to apoptosis of virally infected cells without increasing
      production of infectious virus. Alternatively, the replication and maintenance of
      the human herpesvirus-8 episome during latency can be disrupted by glycyrrhizic
      acid or hydroxyurea so that the virus no longer contributes to tumorigenesis.
      Both the innate and acquired immune systems can also be augmented to help prevent
      or treat human herpesvirus-8-associated tumors. SUMMARY: Novel strategies
      targeting human herpesvirus-8, which is present in all cases of Kaposi's sarcoma
      and primary effusion lymphoma, provide opportunities for selectively killing
      tumor cells.

PMID- 16093795
TI  - Vaccine strategies for human papillomavirus-associated cancers.
AB  - PURPOSE OF REVIEW: To review novel immunologic strategies for the prevention and
      treatment of human papillomavirus infection and associated diseases. Both animal
      model systems and human protocols are discussed. RECENT FINDINGS: Many vaccine
      platforms for both prevention of human papillomavirus infection and treatment of
      associated disease have been developed. Virus-like particle constructs containing
      human papillomavirus capsid proteins have been shown to protect against human
      papillomavirus infection. Novel peptide or protein constructs containing modified
      E6 or E7 proteins, novel adjuvants, fusion proteins such as immunoglobulin-G
      heavy chain E7, or heat shock proteins have been made as therapeutic modalities.
      In addition, many new recombinant vaccine vectors such as vaccinia, Listeria
      species, adenovirus, Semliki Forest vectors, and others have been developed as
      carriers of immunotherapeutic agents. Recently, chimeric virus-like particle
      vaccines have been developed to treat existing human papillomavirus-induced
      neoplasms. SUMMARY: Immunotherapy protocols using a variety of recombinant
      vectors and modified human papillomavirus proteins induce in-vitro T cell
      responses and may lead to tumor regression. Vaccine-induced in-vitro immune
      reactivity and clinical vaccine effects are often not well associated. Further
      analysis of ongoing human immunotherapy trials is awaited.

PMID- 16093796
TI  - Rituximab for HIV-associated lymphoma: weighing the benefits and risks.
AB  - PURPOSE OF REVIEW: This review discusses the potential benefits and risks of
      using the anti-CD20 monoclonal antibody rituximab for the treatment of HIV
      associated B-cell non-Hodgkin's lymphoma. RECENT FINDINGS: Studies have
      consistently demonstrated that rituximab improves response and survival when
      combined with standard chemotherapy compared with chemotherapy alone in
      immunocompetent patients with intermediate-grade non-Hodgkin's lymphoma. Several
      recently reported phase II and III trials have evaluated the use of rituximab
      plus chemotherapy for HIV-associated B-cell non-Hodgkin's lymphoma. Phase II
      trials combining rituximab with either standard cyclophosphamide, doxorubicin,
      vincristine, and prednisone (CHOP) chemotherapy or infusional chemotherapy have
      reported encouraging results, suggesting a similar benefit in HIV-positive
      individuals. A phase III trial comparing CHOP with CHOP-plus rituximab (R-CHOP)
      demonstrated a lower risk from progression of the lymphoma, but a higher risk of
      early and late infectious-related death in patients with a low CD4 count (<
      50/microL). SUMMARY: Rituximab should be used cautiously in patients with
      advanced HIV infection who have a CD4 count of less than 50/microL, as it seems
      to increase the risk of developing fatal infectious complications. In patients
      with higher CD4 counts, the benefit of rituximab may outweigh its risk, although
      this has yet to be confirmed in prospective, randomized trials specifically
      performed in this population.

PMID- 16093797
TI  - Multidrug resistance in AIDS-related lymphoma.
AB  - PURPOSE OF REVIEW: AIDS-related lymphoma has a decreased response rate and poorer
      prognosis to standard chemotherapy when compared with lymphoma in the non-HIV
      population. In addition to the known HIV-related and lymphoma-related poor
      prognostic factors, this review discusses another factor, MDR-1 expression and
      its impact on response to therapy in patients with AIDS-related lymphoma. RECENT
      FINDINGS: There is an increased incidence of de-novo MDR-1 expression in AIDS
      related lymphoma compared with lymphoma in the non-HIV settings. MDR-1 expression
      in AIDS-related lymphoma is associated with poor response to conventional
      combination chemotherapy. Liposomal encapsulation of doxorubicin when substituted
      for doxorubicin in the CHOP regimen (cyclophosphamide, doxorubicin, vincristine,
      prednisone) seems to overcome P-glycoprotein-mediated drug resistance in AIDS
      related lymphoma. SUMMARY: The overexpression of MDR-1 gene product P
      glycoprotein is an adverse prognostic factor in AIDS-related lymphoma. Treatment
      with liposomal encapsulated doxorubicin seems to overcome the P-glycoprotein
      related drug resistance. This and other strategies to modulate MDR-1 should be
      further explored in order to improve success rates in the treatment of AIDS
      related lymphoma.

PMID- 16093798
TI  - Human T cell lymphotropic virus-associated leukemia/lymphoma.
AB  - PURPOSE OF REVIEW: This article summarizes the current pathophysiologic basis for
      human T cell lymphotropic virus-associated leukemia/lymphoma as well as past,
      present, and future therapeutic options. RECENT FINDINGS: New studies have been
      published on allogeneic stem cell transplantation, arsenic trioxide, and
      bortezomib for this condition. SUMMARY: Studies of the molecular biology of human
      T cell lymphotropic virus-1-induced T cell leukemia/lymphoma have defined a
      critical role for oncoprotein, Tax, and activation of nuclear factor kappaB
      transcription pathways, which have provided rational approaches to improved
      therapy for T cell leukemia/lymphoma as well as a model for other hematopoietic
      malignancies characterized by nuclear factor kappaB activation.

PMID- 16093799
TI  - Aerodigestive cancers in HIV infection.
AB  - PURPOSE OF REVIEW: Aerodigestive (lung, head and neck) cancers are among the most
      prevalent and deadly neoplasms worldwide, and the incidence rates are rising.
      Given the improvements in life expectancy of persons with HIV/AIDS when treated
      with highly active antiretroviral agents, persons with HIV infection are
      therefore increasingly likely to develop these malignancies. This chapter focuses
      on the epidemiology of these malignancies and reviews the most recent literature
      and current understanding of the causes and treatment of these malignancies in
      HIV-positive populations. RECENT FINDINGS: Aerodigestive neoplasms in patients
      with HIV infection are associated with younger age at diagnosis, cigarette
      smoking, advanced stage at presentation, and a more aggressive clinical course.
      The causes of these cancers, aside from the traditional risk factors of tobacco
      and alcohol exposure, are not clear. Although these neoplasms are non-AIDS
      defining, factors that might contribute to risk include HIV-related
      immunosuppression and co-infection with high-risk human papillomavirus subtypes.
      SUMMARY: With continued improvements in therapies for HIV, the expected increase
      in incidence and mortality of persons with HIV infection from aerodigestive
      malignancies will likely become a major public health concern. Given the younger
      age of HIV-infected patients with these malignancies and the apparently higher
      rates of smoking among HIV-positive individuals, aggressive smoking cessation
      efforts should be directed to this high-risk population.

PMID- 16093800
TI  - Antiretroviral therapy: an update for the non-AIDS specialist.
AB  - PURPOSE OF REVIEW: The treatment of HIV infection has been transformed by the
      introduction of highly active antiretroviral therapy. For patients who respond
      and can tolerate lifelong therapy, HIV infection may become a chronic disease
      requiring long-term ambulatory care follow-up. The current management of
      antiretrovirals is increasingly complex because of the large number of agents,
      wide spectrum of toxicities, adherence issues, and drug interactions. This review
      summarizes the currently available agents, recommended and alternative
      combinations, commonly encountered adverse events, and viral resistance issues.
      RECENT FINDINGS: Twenty antiretroviral medications are commercially available in
      the United States. Six new agents have been introduced since 2000, including one
      drug in a novel class of HIV fusion inhibitors. The adverse effects of
      antiretrovirals are well characterized and include lactic acidosis related to
      nucleoside reverse transcription inhibitors; metabolic and body habitus changes,
      primarily attributed to protease inhibitors; and concern about the long-term
      vascular consequences of elevated lipids and insulin resistance associated with
      treatment. The recommended antiretroviral therapy by an expert panel as of
      October 2004 is summarized. SUMMARY: The benefits of antiretroviral therapy are
      clear: reduced morbidity and mortality related to advanced HIV infection.
      Managing antiretroviral therapy, along with their adverse effects and drug
      interactions, is complex. Modern treatment mandates a thorough understanding of
      the agents. Consultation with an HIV-experienced clinician should be considered
      in most circumstances.

PMID- 16093801
TI  - Management of locally advanced cervical cancer.
AB  - PURPOSE OF REVIEW: Cervical cancer is a significant global public health problem.
      In underdeveloped countries where screening programs are not widely available and
      in underserved populations in developed countries, women commonly present with
      locally advanced disease that is not curable by any extent of radical
      hysterectomy. This review will critically evaluate the evidence supporting the
      available treatment modalities for locally advanced cancer of the uterine cervix.
      RECENT FINDINGS: Concurrent cisplatin-based chemotherapy and radiation have
      demonstrated significant survival improvement for patients with locally advanced
      cervical cancer. Advances in imaging and radiotherapy technologies, the inclusion
      of newer agents to the chemoradiation regimens, the use of new hypoxic cell
      radiosensitizers and monoclonal antibodies that inhibit cell growth, with
      consequent increase in malignant cell kill fractions, are some of the new
      therapeutic options that may be used to improve the survival of these patients.
      SUMMARY: Continued improvement in understanding the natural history of cervical
      cancer, the limitations of the current staging system, and these newer
      therapeutic options will increase the efficacy of chemoradiation and improved the
      survival of these patients.

PMID- 16093802
TI  - Hormone replacement therapy after cancers.
AB  - PURPOSE OF REVIEW: The role of female hormones in estrogen-dependent cancers has
      been debated for years. This is particularly true of breast cancer.
      Retrospective, case, and cohort control studies usually have suggested no
      influence. The Women's Health Initiative study in 2002, a prospective double
      blind study, noted an increased risk of breast cancer if estrogen plus
      progesterone was given. In the estrogen-only arm of that study, a decreased (not
      significant) risk of breast cancer was noted. With this controversy, can estrogen
      be given safely to a woman who has been treated for breast cancer? The relation
      between endometrial cancer and unopposed estrogen is well established. With clear
      cut evidence of this relation, is there evidence to suggest a role for
      replacement therapy in women who have been treated for endometrial cancer? RECENT
      FINDINGS: Several case-control and cohort studies have noted either no increased
      risk or actually less risk of recurrence in women taking estrogen after therapy
      after breast cancer. Although the general consensus is that such a recommendation
      is contraindicated, the data do not support this admonition. The current data
      suggest that replacement therapy can be given to the woman who has been treated
      for endometrial cancer. SUMMARY: There seems to be little if any risk in giving
      hormone replacement therapy to women who have had breast or endometrial cancer.
      There are no data to suggest that hormone replacement therapy is contraindicated
      in women who have been treated for cervical or ovarian cancer.

PMID- 16093803
TI  - What's new in systemic therapy for endometrial cancer.
AB  - PURPOSE OF REVIEW: Endometrial cancer is one of the most common gynecologic
      cancers. Most women present with early disease that is curable. In women with
      poor prognostic factors or advanced disease, survival is greatly diminished.
      Recently there have been several trials of adjuvant treatment and treatment for
      advanced and recurrent endometrial cancer. These trials of systemic therapy will
      be reviewed. RECENT FINDINGS: Several areas have been the focus of recent
      literature on systemic therapy for endometrial cancer. These include large phase
      III trials of multi-agent chemotherapy regimens for advanced and recurrent
      endometrial cancer, combined chemotherapy and radiotherapy treatments, and novel
      targeted agents. SUMMARY: New approaches to combining the traditional adjuvant
      modalities for high-risk endometrial cancer as well as combining new novel agents
      with traditional chemotherapeutics will improve patient outcomes.

PMID- 16093804
TI  - The role of surgery in ovarian cancer with special emphasis on cytoreductive
      surgery for recurrence.
AB  - PURPOSE OF REVIEW: The role of cytoreductive surgery for recurrent ovarian cancer
      has not clearly been defined, and randomized trials are lacking. Some series have
      reported favorable outcomes for selected patients. This review summarizes the
      available evidence for selecting patients and the results of cytoreductive
      surgery in recurrent ovarian cancer. RECENT FINDINGS: A Medline search identified
      23 series including 1795 patients (21-285 patients per study). Patients who
      underwent cytoreductive surgery for recurrence were highly selected. Complete
      tumor resection was feasible in 9 to 82% of patients and was commonly associated
      with prolonged survival. A variety of predictive and prognostic factors for
      complete resection were reported. Good performance status, disease
      characteristics (e.g. peritoneal carcinosis), and outcome of prior surgery seemed
      to have an impact on surgical outcome. By contrast, disease-free survival played
      only a minor role, especially in patients with recurrence later than 6 months
      after primary treatment. SUMMARY: Prospective evaluation of predictive scores for
      successful cytoreductive surgery in recurrent ovarian cancer is urgently needed.
      In a second step, randomized trials evaluating the role of surgery in the
      treatment strategy of recurrent ovarian cancer should be initiated. Until then,
      experienced and trained surgeons might offer surgery for recurrent disease to
      individually selected patients after giving information about the potential
      benefit and about the limited available evidence regarding this strategy.

PMID- 16093805
TI  - Bibliography. Current world literature. Lymphoma.

PMID- 16093806
TI  - Subcutaneous unfractionated heparin compared with low-molecular-weight heparin
      for the initial treatment of venous thromboembolism.
AB  - PURPOSE OF REVIEW: Low-molecular-weight heparin is the preferred choice for the
      initial treatment of acute, uncomplicated venous thromboembolism. In this
      context, unfractionated heparin is as safe and effective as low-molecular-weight
      heparin but requires strict laboratory monitoring. Twice-daily subcutaneous
      unfractionated heparin is more effective than, and as safe as, intravenous
      unfractionated heparin and may simplify patient treatment in or out of the
      hospital, being possibly cost saving, especially if it is used in weight-based,
      fixed, unadjusted doses. The present review focuses on the relative values of low
      molecular-weight heparin and subcutaneous unfractionated heparin for the initial
      treatment of venous thromboembolism. RECENT FINDINGS: The major advantages of low
      molecular-weight heparin over unfractionated heparin seem to be ease of
      administration and cost savings associated with home therapy or early hospital
      discharge; however, many patients with venous thromboembolism are still admitted
      to the hospital for treatment, and unfractionated heparin is extensively used to
      this purpose, especially in the United States. Subcutaneous unfractionated
      heparin, adjusted according to activated partial thromboplastin time algorithms,
      is as safe and effective as low-molecular-weight heparin for the treatment of
      venous thromboembolism, allows for quick mobilization and early discharge of
      suitable patients, and represents a cost-effective strategy. Fixed-dose
      unfractionated heparin, like low-molecular-weight heparin, may be used for the
      home treatment of deep vein thrombosis. SUMMARY: Subcutaneous unfractionated
      heparin, targeted on activated partial thromboplastin time results or in fixed
      doses, may be used in or out of the hospital for the treatment of venous
      thromboembolism, being possibly cost effective; however, these findings need
      confirmation through appropriate, large-sample, randomized clinical trials.

PMID- 16093807
TI  - Anticoagulation therapy in the antiphospholipid syndrome: recent advances.
AB  - PURPOSE OF REVIEW: The antiphospholipid syndrome is currently best treated with
      anticoagulation. This review discusses the recent literature addressing the
      duration, intensity, and appropriateness of anticoagulation or antiplatelet
      therapy in various clinical subcategories of this syndrome. RECENT FINDINGS:
      Several recent articles reaffirm the benefits of long-term anticoagulation in
      patients with venous thromboembolism or undergoing renal transplantation and
      support recommendations for usual International Normalized Ratio targets. Aspirin
      seems to confer benefits similar to those of anticoagulation in arterial stroke.
      Appropriate anticoagulation strategies for pregnancy are controversial. SUMMARY:
      Anticoagulation will remain the mainstay of treatment for most patients with
      antiphospholipid syndrome. The optimal therapy for specific subgroups of patients
      will, however, require further good-quality studies.

PMID- 16093808
TI  - Perioperative bridging interruption with heparin for the patient receiving long
      term anticoagulation.
AB  - PURPOSE OF REVIEW: To provide a timely and concise review of the most recent
      clinical data in the field of bridging (anticoagulation) therapy with heparin for
      the at-risk patient receiving long-term oral anticoagulation who requires
      temporary interruption for an elective invasive procedure or surgery. RECENT
      FINDINGS: A recent systematic review found that the quality of studies of
      bridging therapy published before June 2001 was generally poor. More recent
      larger prospective cohort studies and registries of patients receiving long-term
      oral anticoagulation, including patients with mechanical heart valves, who
      underwent bridging therapy with mostly treatment-dose low-molecular-weight
      heparin for both major and non-major elective invasive procedures or surgeries
      have been completed. These studies reveal an overall thromboembolic complication
      rate of 1.22 (95% CI 0.81-1.77) and an overall major bleed rate of 2.94 (95% CI
      2.28-3.74). Standardized low-molecular-weight heparin bridging regimens using
      postoperative bleeding risk assessments optimized good clinical outcomes, and
      bridging therapy with low-molecular-weight heparin appears to be at least as safe
      as unfractionated heparin and produces substantial cost savings through reduction
      in length of stay in the hospital. SUMMARY: Perioperative bridging therapy with
      heparin, either unfractionated heparin or low-molecular-weight heparin, appears
      to be safe and effective for patients, including those with mechanical heart
      valves, receiving long-term oral anticoagulation who require temporary
      interruption, especially for non-high-bleeding risk procedures such as minor
      surgery and invasive procedures. Further studies, including randomized double
      blind placebo-controlled trials, are needed to optimize bridging therapy for
      specific patients and procedures.

PMID- 16093809
TI  - Prognostic value of echocardiography and spiral computed tomography in patients
      with pulmonary embolism.
AB  - PURPOSE OF REVIEW: The identification of patients with pulmonary embolism who are
      at risk for mortality or severe morbidity in the early observation period is
      important because these patients may benefit from more aggressive initial
      treatment such as thrombolysis or catheter removal of the thrombus. Right
      ventricular dysfunction has been suggested to have a prognostic value for the
      occurrence of these adverse outcomes. The purpose of this review is to determine
      the prevalence and prognostic value of right ventricular dysfunction, in
      particular in normotensive patients with pulmonary embolism. The association
      between right ventricular dysfunction and outcome of pulmonary embolism was
      evaluated for studies using echocardiography, spiral computed tomography, or both
      to detect right ventricular dysfunction. RECENT FINDINGS: Seven studies using
      echocardiography with a total of 3468 patients and six studies using spiral
      computed tomography with a total of 868 patients were identified. The prevalence
      of right ventricular dysfunction with echocardiography in normotensive patients
      was approximately 30 to 40%, with a positive predictive value for short-term
      mortality of approximately 5%. These indices could not be calculated for
      normotensive patients in the studies that used spiral computed tomography.
      SUMMARY: The studies using echocardiography show that there is an association
      between right ventricular dysfunction and prognosis of pulmonary embolism in
      normotensive patients. Whether this is clinically useful in guiding more
      aggressive therapy remains to be determined, however. Thus far, the results of
      the studies with spiral computed tomography are too preliminary to enable
      definite conclusions to be drawn for the normotensive patient group.

PMID- 16093810
TI  - Unfractionated heparin compared with low-molecular-weight heparin as related to
      heparin-induced thrombocytopenia.
AB  - PURPOSE OF REVIEW: Heparin-induced thrombocytopenia is a severe side effect of
      treatment with unfractionated heparin. The relation of low-molecular-weight
      heparin to heparin-induced thrombocytopenia is less well understood. This review
      will summarize what is known about the similarities and differences between
      thrombocytopenia induced by low-molecular-weight heparin and that induced by
      unfractionated heparin. RECENT FINDINGS: The pathophysiology of unfractionated
      heparin-induced thrombocytopenia, caused by the development of antibodies to
      heparin/platelet factor 4 complexes, holds true for low-molecular-weight heparin
      because the molecules of the latter are of the same saccharidic structure as
      those of unfractionated heparin. Owing to their smaller size, however, low
      molecular-weight heparin does not interact with platelet factor 4 and platelets
      as efficiently as does unfractionated heparin. This translates to a two- to
      threefold lower risk of immune sensitization (antibody generation and occurrence
      of clinical heparin-induced thrombocytopenia). Low-molecular-weight heparin
      induced thrombocytopenia antibodies are more often immunoglobulin A and
      immunoglobulin M, in contrast to the immunoglobulin G antibodies generated with
      unfractionated heparin-induced thrombocytopenia, which tend to be more often
      associated with clinical heparin-induced thrombocytopenia. The clinical
      expression of low-molecular-weight heparin-induced thrombocytopenia is generally
      similar to that of unfractionated heparin-induced thrombocytopenia but can have a
      slower onset, more severe thrombocytopenia, and slower platelet count recovery.
      Given that low-molecular-weight heparin, of itself, is linked with heparin
      induced thrombocytopenia pathophysiology and it can interact with most
      preexisting heparin-induced thrombocytopenia antibodies generated after exposure
      to unfractionated heparin, treatment of heparin-induced thrombocytopenia patients
      with low-molecular-weight heparin is contraindicated. SUMMARY: The risk of the
      development of heparin-induced thrombocytopenia with low-molecular-weight heparin
      treatment is reduced relative to the frequency of unfractionated heparin-induced
      thrombocytopenia, but it is not eliminated, and platelet counts should be
      monitored with treatment.

PMID- 16093811
TI  - Low-molecular-weight heparin for the prevention of postoperative venous
      thromboembolism after abdominal surgery: a review.
AB  - PURPOSE OF REVIEW: To analyze the effect of low-molecular-weight heparin in
      abdominal surgery, which carries a significant risk of thrombosis, a risk further
      increased by cancer. RECENT FINDINGS: Searches in EMBASE and PubMed between 1980
      and 2004 were conducted to identify studies of thromboprophylaxis in abdominal
      surgery patients. Sixteen comparative studies were identified. They showed that
      low-molecular-weight heparin is as effective as unfractionated heparin in
      reducing venous thromboembolism and, at appropriate doses, can reduce bleeding
      complications. In very-high-risk cancer patients, a higher dose of low-molecular
      weight heparin may offer increased efficacy without increasing the risk of
      bleeding. Extending the standard 7-10-day low-molecular-weight heparin
      prophylaxis period may benefit certain high-risk patient groups. SUMMARY:
      Patients undergoing abdominal surgery should be stratified according to
      thromboembolism risk and given prophylaxis accordingly. Low-molecular-weight
      heparin is a recommended alternative to unfractionated heparin in moderate- or
      high-risk patients. In patients with cancer, high doses of low-molecular-weight
      heparin may offer increased efficacy without increased bleeding, and an extended
      4-week period of prophylaxis could be beneficial.

PMID- 16093812
TI  - Age as a risk factor for venous thromboembolism after major surgery.
AB  - PURPOSE OF REVIEW: Postoperative deep venous thrombosis and pulmonary embolism
      are serious and potentially life-threatening complications that frequently occur
      after major surgery. Most guidelines for thromboprophylaxis use advancing age as
      a key component to estimate thromboembolic risk. The reported effect of age on
      postoperative venous thromboembolism varies widely, making it unclear whether age
      alone is a significant risk factor. This article reviews the recent literature on
      the effect of age on the incidence of postoperative venous thromboembolism.
      RECENT FINDINGS: Between 2003 and 2005, several cohort studies assessed the risk
      factors for postoperative venous thromboembolism, showing a variable effect of
      age on its incidence in the 2- to 3-month period after major surgery. Studies
      also revealed a significant difference in the effect of age on the incidence of
      venous thromboembolism depending on the type of surgery. Obesity, postoperative
      immobilization, the use of thromboprophylaxis, the nature of the surgery, and
      underlying comorbid conditions such as heart failure seem to have a greater
      influence on the risk of venous thromboembolism than does age. SUMMARY: The
      variation in the effect of age on postoperative venous thromboembolism likely
      depends on whether or not other comorbid conditions or age-related changes in
      functional status are considered as risk factors. When these other risk factors
      are taken into account, the effect of advanced age decreases. More research is
      needed to develop validated venous thromboembolism risk-prediction tools for
      specific types of surgery. By use of this information, the intensity and duration
      of postoperative thromboprophylaxis can be tailored to the level of risk, not
      just age alone.

PMID- 16093813
TI  - Effect of anticoagulant drugs in cancer.
AB  - PURPOSE OF REVIEW: The aim of this review is to perform a critical analysis of
      all completed studies evaluating the role of anticoagulant agents in improving
      survival in patients with cancer. Furthermore, the rationale for testing
      anticoagulant drugs in this setting, and the recent basic research studies
      providing new evidence for a link between tissue malignant transformation of
      tissues and hemostatic proteins, are also briefly reviewed. RECENT FINDINGS: Four
      prospective randomized clinical studies to test the impact of low-molecular
      weight heparin on mortality in cancer patients have been published. The results
      suggest a benefit from treatment, particularly in patients with nonadvanced
      disease. Inhibition of specific clotting pathways by anticoagulants may be
      hypothesized, particularly those involved in the malignant behavior of tissues.
      In the same vein, a direct action of anticoagulants on mechanisms of tumor growth
      and progression can be considered. SUMMARY: An antineoplastic effect of
      anticoagulant agents has often been suggested. Heparin and vitamin K antagonists
      have both been tested in this context. Heparin has been more extensively studied.
      Data from clinical trials of thromboprophylaxis in cancer patients have suggested
      that heparin may have beneficial effects on survival in these patients, with a
      major role for low-molecular-weight heparin compared with unfractionated heparin.
      Recently, the results of new prospective randomized clinical trials to evaluate
      the effect of low-molecular-weight heparin on cancer survival have become
      available. The published data look promising and provide an important step
      forward in the research knowledge in this field.

PMID- 16093814
TI  - Paraproteinemias and the lungs.

PMID- 16093815
TI  - Chronic cough in adults with interstitial lung disease.
AB  - PURPOSE OF REVIEW: Although dyspnea is the most common and distressing symptom in
      patients with chronic interstitial lung disease, chronic cough, a potentially
      debilitating symptom that impairs health-related quality of life, has been
      described as another common symptom in these patients. RECENT FINDINGS: Many
      patients with interstitial lung disease have their chronic cough mistakenly
      attributed to that condition when, in fact, the cough is due to more common
      disorders such as asthma, upper airway cough syndrome (previously referred to as
      postnasal drip syndrome), or gastroesophageal reflux disease. This article
      presents new data on a select group of patients and shows that more than 50% of
      patients with interstitial lung disease who are referred to a cough clinic for
      evaluation can have cough caused by these other more common causes of chronic
      cough. It is also clear, however, that chronic interstitial lung disease, by
      itself, can cause chronic cough, perhaps related to an increased cough reflex
      sensitivity. SUMMARY: Clinicians should be cautious when ascribing chronic cough
      to interstitial lung disease without first completely evaluating for other
      possible causes of cough. When cough is attributed to interstitial lung disease,
      therapy, when available, should be directed at the specific underlying diagnosis.
      Corticosteroids may be helpful in alleviating chronic cough in some cases of
      interstitial lung disease, but, because of the potential side effects of
      corticosteroids and lack of proven efficacy for some types of interstitial lung
      disease (e.g. idiopathic pulmonary fibrosis), treatment should weigh the risks
      and benefits for each patient individually. Nonspecific antitussive therapies
      shown to be clinically effective for chronic cough in general are codeine and
      dextromethorphan, but these have not been studied specifically in interstitial
      lung disease.

PMID- 16093816
TI  - The role of bronchoalveolar lavage in diffuse parenchymal lung diseases.
AB  - PURPOSE OF REVIEW: To evaluate the role of bronchoalveolar lavage in the
      diagnosis of diffuse parenchymal lung diseases and review the recent literature
      published within the past 12 months. RECENT FINDINGS: Diffuse parenchymal lung
      diseases are a heterogeneous group of disorders originating from the distal lung
      parenchyma. Despite different etiologies, the clinico-radiologic findings are
      usually alike and diagnosis can be challenging. Bronchoalveolar lavage and the
      analysis of cell counts are routine investigations for this group of disorders.
      Not only it can be used to see serial changes, it also important for providing
      information from a broader lung area. Although rarely diagnostic for a particular
      etiology, the predictive value of bronchoalveolar lavage differentials are
      reported to make some diagnoses more likely and exclude others like infections
      and tumors. This result is especially significant for the frequently encountered
      diffuse parenchymal diseases like sarcoidosis, usual interstitial pneumonia or
      extrinsic allergic alveolitis. SUMMARY: Bronchoalveolar lavage is a convenient
      and safe procedure to apply for the diagnosis of diffuse parenchymal lung
      diseases especially to provide more information of the likelihood of the more
      common forms like sarcoidosis, extrinsic allergic alveolitis and usual
      interstitial pneumonia.

PMID- 16093817
TI  - The organizing pneumonias: an update and review.
AB  - PURPOSE OF REVIEW: Basic information as well as more recent concepts regarding
      cryptogenic organizing pneumonia and secondary forms of the disease. RECENT
      FINDINGS: More recently described and less well recognized illnesses associated
      with organizing pneumonia, such as organizing pneumonia associated with
      radiation, are enumerated. In vitro studies from separate laboratories are
      integrated to create a proposed model of the pathogenesis and repair mechanisms
      that occur in organizing pneumonias. Using current criteria, we note other
      interstitial lung processes, in addition to organizing pneumonia, are present in
      some earlier reports. SUMMARY: Cryptogenic organizing pneumonia has been reported
      to respond to corticosteroids with clinico-radiographic resolution in 70-80% of
      cases. Treatment duration is lengthy, and despite this, recurrences and late
      recurrences are common. Rapidly progressive, steroid resistant and poor
      prognostic forms of organizing pneumonia have been described and have been
      reported more frequently with secondary organizing pneumonia. Since other
      histologic interstitial patterns often coexist with organizing pneumonia, tissue
      sampling error or an incorrect morphologic diagnosis can be the reason for
      aggressive clinical behavior. Steroid nonresponsive patients have been treated
      with secondary non-steroidal agents. Good clinical outcomes have been reported.
      Inhaled antigens stimulate GM-CSF-mediated airway inflammation in organizing
      pneumonia. Repair requires the following: granulation tissue, upon which re
      epithelialization occurs; a favorable stromal ratio of matrix metalloproteinase
      to tissue inhibitors of metalloproteinase; concurrent resolution of inflammation;
      and stromal fibroblast ingestion of collagen produced earlier in repair,
      reversing the initial fibrosis.

PMID- 16093818
TI  - Does interstitial lung disease predispose to lung cancer?
AB  - PURPOSE OF REVIEW: This review examines the evidence for the causality and
      pathogenesis of lung cancer associated with interstitial lung disease. RECENT
      FINDINGS: Although cigarette smoking is the leading cause of lung cancer, several
      other conditions either predispose to lung cancer or increase the risk of lung
      cancer in smokers. The evidence supports an increased risk of lung cancer due to
      specific fibrotic and inflammatory lung diseases (termed interstitial lung
      diseases), including idiopathic pulmonary fibrosis, systemic sclerosis, and
      certain pneumoconioses. The potential pathogenetic mechanisms indicate that
      recurrent injury and inflammation result in genetic alterations that predispose
      to lung cancer. SUMMARY: Idiopathic pulmonary fibrosis, systemic sclerosis, and
      certain pneumoconioses are associated with an independent increased risk of lung
      cancer; however, a unifying pathogenetic mechanism to explain the causality of
      this association has not been described. In addition, the inconsistently reported
      lung cancer frequencies call attention to the need for prospective studies of
      good quality.

PMID- 16093819
TI  - Autoimmunity and interstitial lung disease.
AB  - PURPOSE OF REVIEW: The pathogenesis of idiopathic pulmonary fibrosis as well as
      that of several other interstitial lung diseases is poorly understood. The role
      of autoimmunity in interstitial lung diseases associated with connective tissue
      disorders such as systemic sclerosis, systemic lupus erythematosus, and
      rheumatoid arthritis as well as the vasculitides is well established. There is at
      least some evidence in the literature that supports the role of autoimmunity as
      one of the mechanisms of alveolar injury responsible for idiopathic pulmonary
      fibrosis. This review is an attempt to summarize the studies on this subject.
      RECENT FINDINGS: Repeated extraneous insults and exposures are considered to be
      responsible for recurrent alveolar injury, inflammation, dysregulated tissue
      repair, and fibroproliferation resulting in pulmonary fibrosis. The presence of
      autoantibodies in the sera of patients with idiopathic pulmonary fibrosis has
      been demonstrated in a few studies. Several autoantibodies, including anti-Sm
      antibodies, antibodies to U1 ribonucleoproteins, and antibodies to U3
      ribonucleoproteins, have been demonstrated in connective tissue disorders, many
      of which are associated with interstitial lung involvement. Autoimmunity has been
      also suggested as a possible mechanism of rejection caused by bronchiolitis
      obliterans after lung transplantation. SUMMARY: It might seem that the role of
      autoimmunity in interstitial lung disease has been underestimated or even
      underinvestigated. The subject requires further investigation, especially with
      regard to the problems of lung allograft rejection due to bronchiolitis
      obliterans of nonalloimmunity origin and the failure of patients with idiopathic
      pulmonary fibrosis to respond to most forms of currently available therapy.

PMID- 16093820
TI  - Pulmonary involvement in microscopic polyangiitis.
AB  - PURPOSE OF REVIEW: Microscopic polyangiitis is a systemic necrotizing vasculitis
      that affects small vessels, resulting in a wide spectrum of organ involvement
      including the kidneys and the lungs. This paper reviews recent insights and
      observations into the pathogenesis, clinical manifestations, and treatment of
      pulmonary involvement in microscopic polyangiitis. RECENT FINDINGS: The spectrum
      of clinical presentations ranges from antecedent interstitial fibrosis to frank
      hemoptysis secondary to capillaritis. Computerized tomography imaging reveals a
      variety of pulmonary findings, including ground-glass attenuation, consolidation,
      thickening of bronchovascular bundles, and honeycombing. Antineutrophil
      cytoplasmic antibodies are important in diagnosis as well as in the pathogenesis
      and prognosis of microscopic polyangiitis. There is more evidence to support the
      various therapeutic modalities currently used in pulmonary manifestations of
      microscopic polyangiitis, including induction therapy with cyclophosphamide, the
      use of other novel pharmacologic agents such as the tumor necrosis factor-alpha
      blockers and rituximab, and nonpharmacologic modalities such as plasmapheresis
      and ventilatory management. SUMMARY: The pulmonary manifestations of microscopic
      polyangiitis are diverse and often difficult to manage; however, as our
      understanding and experience grows so does our ability to successfully diagnose
      and treat these patients.

PMID- 16093821
TI  - Pulmonary hypertension in interstitial lung disease.
AB  - PURPOSE OF REVIEW: Exercise impairment and pulmonary hypertension are common
      features of interstitial lung disease. Antifibrotic therapies for interstitial
      lung disease remain unproved; therefore, some interest has been focused on
      treating the pulmonary vascular impairment these diseases. RECENT FINDINGS:
      Patients with pulmonary hypertension secondary to idiopathic pulmonary fibrosis
      may have normal resting pulmonary artery pressure, but it often rises with
      exercise. Exercise impairment in idiopathic pulmonary fibrosis has a strong
      correlation with the degree of pulmonary artery pressure elevation, and
      hypoxemia, a hallmark of pulmonary hypertension, strongly correlates with
      survival. SUMMARY: Small case series have shown that some patients improve on
      receiving therapy for pulmonary hypertension secondary to interstitial lung
      disease. These findings suggest that larger treatment trials for medications
      targeting pulmonary hypertension in interstitial lung disease are warranted.

PMID- 16093822
TI  - Epstein-Barr-virus-induced interstitial lung disease.
AB  - PURPOSE OF REVIEW: We describe a patient in whom Epstein-Barr virus infection
      appears to have caused an unusual interstitial lung disease with multisystem
      involvement resembling sarcoidosis and interstitial lung disease. We have
      reviewed the relevant literature about the relation of Epstein-Barr virus and
      interstitial lung disease. RECENT FINDINGS: Epstein-Barr virus replication within
      type II alveolar cells was shown to occur in adult cryptogenic fibrosing
      alveolitis. Latent membrane protein 1 is one of the Epstein-Barr-virus-associated
      proteins and is expressed on the surface of Epstein-Barr-virus-infected cells in
      the latent and replicating phases. Latent membrane protein 1 was positive in the
      cuboidal epithelial cells of the lungs from some patients with idiopathic
      pulmonary fibrosis, and that its positivity correlated with poor prognosis.
      Epstein-Barr virus was also found in the lungs of children with lymphocytic
      interstitial pneumonia, AIDS and Langerhans cell histiocytosis. Epstein-Barr
      virus DNA was not detectable in patients with sarcoidosis. There was also lack of
      evidence for a role of Epstein-Barr virus in the increase of lung cancer in
      idiopathic pulmonary fibrosis. SUMMARY: Using monoclonal antibodies against viral
      antigen Epstein-Barr virus was shown to replicate within type II alveolar cells
      of adult idiopathic pulmonary fibrosis patients. Latent membrane protein
      1positivity indicates poor prognosis; Epstein-Barr virus positivity did not
      increase the incidence of lung cancer in these patients. Epstein-Barr virus was
      also associated with lymphocytic interstitial pneumonia, AIDS and Langerhans cell
      histiocytosis but not with sarcoidosis.

PMID- 16093824
TI  - Bibliography. Current world literature. Disorders of pulmonary circulation.

PMID- 16093823
TI  - Lung transplantation and interstitial lung disease.
AB  - PURPOSE OF REVIEW: Interstitial lung disease includes a heterogeneous group of
      disorders that leads to respiratory insufficiency and death in a significant
      number of patients. Lung transplantation is a therapeutic option in select
      candidates. RECENT FINDINGS: The indications, transplant procedure options, and
      outcomes continue to evolve. Various recipient comorbidities influence the choice
      of procedure in patients with interstitial lung disease. Single lung transplants
      are used as the procedure of choice and bilateral transplants are reserved for
      patients with suppurative lung disease and patients with pulmonary hypertension.
      Issues unique to patients with interstitial lung disease affect the morbidity,
      mortality and recurrence of the disease. SUMMARY: Lung transplantation is an
      effective therapy for respiratory failure in interstitial lung disease with
      survival following transplant being similar to that achieved in transplant
      recipients with other diseases.

PMID- 16093825
TI  - Systemic lupus erythematosus and Sjogren's syndrome.

PMID- 16093826
TI  - Sources of autoantigens in systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: A hallmark of systemic lupus erythematosus is the production
      of autoantibodies that recognize nuclear antigens. However, the underlying events
      and mechanisms that lead to the selection of these molecules for the autoimmune
      response remain poorly understood. In this review, we will examine some of the
      proposed explanations for sources of systemic lupus erythematosus-specific
      autoantigens. We will focus on events related to apoptosis, viral infection,
      cytokine production, innate immune system components, and alternative splicing of
      pre-mRNA transcripts. RECENT FINDINGS: Definitive proof of a viral etiology for
      lupus remains elusive. However, recent observations have added to increasing
      evidence that viruses contribute to the bypass of tolerance in systemic lupus
      erythematosus. Also, events associated with apoptosis - most notably proteolytic
      autoantigen cleavage by caspases and granzyme B - have been implicated in the
      initiation of autoimmune responses for over a decade. Results obtained from
      animal models and human systems suggest complex functions for pro-apoptotic
      pathways in the regulation of immune responses. Inducible antigen expression and
      alternatively spliced transcripts may represent additional ways of generating
      autoantigenic material. Finally, toll-like receptor family members may play
      critical roles in the induction of antibody responses to nucleic acids in
      systemic lupus erythematosus. SUMMARY: Several factors may contribute to the
      generation of systemic lupus erythematosus-specific autoantigens. Determining the
      underlying causes of autoantibody production may provide important insight into
      the etiology and pathogenesis of this disease.

PMID- 16093827
TI  - Immune cells and cytokines in systemic lupus erythematosus: an update.
AB  - PURPOSE OF REVIEW: Systemic lupus erythematosus is characterized by overactive B
      cells that differentiate into autoantibody-forming cells, aberrant T cell
      function that provides help to B cells, and the production of pro-inflammatory
      cytokines. This article reviews recent studies unraveling the complex interplay
      between cytokines and lymphocytes in systemic lupus erythematosus. RECENT
      FINDINGS: In systemic lupus erythematosus, T cells are characterized by
      heightened calcium responses early after activation of their surface receptor.
      Alterations of the T cell receptor/CD3 complex, namely the substitution of the
      FcepsilsonRgamma for the T cell receptor zeta chain, and increased mitochondrial
      potentials can account for this 'overexcitable' phenotype. At the same time, this
      heightened calcium signal leads to a block of the transcription of the IL-2 gene,
      a pivotal cytokine for the immune response. The end result is increased
      spontaneous apoptosis and decreased activation-induced cell death of T cells in
      systemic lupus erythematosus that in turn leads to enhanced help to B cells and
      potentially decreased regulatory function. The B cells, on the other hand, are
      shown to be directly activated by immune complexes by way of Toll-like receptors
      independently of T cells. Finally, recent studies have tried to elucidate the
      role of cytokines such as interferon-alpha in systemic lupus erythematosus and,
      following the paradigm of rheumatoid arthritis, to establish targets for
      treatment. SUMMARY: The increased apoptosis and aberrant T cell activation
      coupled with nonspecific activation of B cells lead to the production of auto
      antigen: auto-antibody complexes that are the hallmark of systemic lupus
      erythematosus. Future treatments aiming at correcting the intracellular and
      intercellular signaling abnormalities may prove effective in restoring immune
      tolerance in systemic lupus erythematosus.

PMID- 16093828
TI  - New insights from murine lupus: disassociation of autoimmunity and end organ
      damage and the role of T cells.
AB  - PURPOSE OF REVIEW: This review summarizes current literature on genetic
      regulation of different phenotypes in systemic lupus erythematosus in context of
      end-organ disease. Recent findings conflicting with the current paradigm that
      loss of tolerance to chromatin is the critical step for end-organ injury are
      discussed. RECENT FINDINGS: Systemic lupus erythematosus is a prototype immune
      complex disease with circulating autoantibodies to chromatin, histone proteins,
      Sm/La, and other nuclear and cytoplasmic proteins. Extensive studies have been
      carried out on the regulation of B-cell and autoantibody production in lupus
      mice. However, the hypothesis that autoantibodies are primary mediators of organ
      damage fails to explain the heterogenous presentation in patients. Studies in
      murine models of systemic lupus erythematosus clearly dissociate genetic control
      of autoantibody responses to classic lupus antigens and kidney disease. There is
      increasing evidence to support the role of autoreactive T cells and genetic
      control of end organ susceptibility. These studies suggest complex interactions
      between innate and adaptive immunity resulting in end-organ damage. This review
      focuses on autoimmune responses and renal involvement in spontaneous systemic
      lupus erythematosus using murine models of lupus nephritis. SUMMARY: Studies in
      murine models demonstrate complex genetic interactions regulating spontaneous
      systemic lupus erythematosus. Although detection of serum autoantibodies is
      considered a hallmark for clinical diagnosis of systemic lupus erythematosus,
      recent evidence shows that autoantibodies to classic lupus antigens are neither
      required nor sufficient for end-organ damage. Thus, murine models provide new
      insights into the pathogenesis of systemic lupus erythematosus.

PMID- 16093829
TI  - Genetics of susceptibility and severity in systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: The genetic basis of systemic lupus erythematosus, a complex
      genetic trait, may provide important insights into autoimmune disease. Innovation
      in both practical and theoretical approaches will assist in accelerating the pace
      of discovery and our understanding of pathogenesis. RECENT FINDINGS: Significant
      progress has been made in the last year with respect to the refinement of genetic
      intervals to promising candidate genes involved in systemic lupus erythematosus
      pathogenesis and specific phenotype susceptibility. This review highlights these
      discoveries and suggests platforms that may affect the future of analysis of this
      complex disease. SUMMARY: Understanding the genetic basis for systemic lupus
      erythematosus disease and sub-phenotype susceptibility will have a substantial
      effect on the therapeutic interventions used to care for patients.

PMID- 16093830
TI  - Complement and systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: It is well recognized that the complement system plays
      multiple roles in systemic lupus erythematosus. Activation of the classical
      pathway by immune complexes leads to the generation of inflammatory mediators,
      thus promoting tissue injury. Complement activation also plays an important role
      in the maintenance of tolerance to self-antigens. This review discusses recent
      insights in the role of complement in the pathogenesis of systemic lupus
      erythematosus. RECENT FINDINGS: The antiphospholipid syndrome is a major feature
      of systemic lupus erythematosus. New findings have clearly demonstrated that the
      prothrombotic effects seen in a mouse model of this syndrome depend on complement
      activation, whereas the protective effects of heparin are due to its
      anticomplementary effects rather than its anticoagulant action. Secondly, a
      potential mechanism explaining the association of anti-C1q autoantibodies with
      lupus glomerulonephritis has been elucidated in a mouse model system. SUMMARY:
      New findings have helped to reinforce the role of complement in the etiology and
      tissue damage of systemic lupus erythematosus. These findings point to more
      precise, mechanism-based therapies for autoimmune and inflammatory disease.

PMID- 16093831
TI  - Biomarkers for systemic lupus erythematosus: a review and perspective.
AB  - PURPOSE OF REVIEW: Despite decades of extensive work in the understanding of the
      etiopathogenesis of systemic lupus erythematosus, few biomarkers have been
      validated and widely accepted for this disease. The lack of reliable, specific
      biomarkers not only hampers clinical management of systemic lupus erythematosus
      but also impedes development of new therapeutic agents. This paper reviews
      briefly the historical aspects of systemic lupus erythematosus biomarkers and
      summarizes recent studies on candidate biomarkers. RECENT FINDINGS: Recognizing
      the urgent need for lupus biomarkers, a Lupus Biomarker Working Group has
      recently been initiated to facilitate collaborative efforts aimed at identifying
      and validating biomarkers for systemic lupus erythematosus. Based on available
      data, several laboratory markers have shown promise as biomarkers for
      susceptibility, diagnosis, and disease activity. These include Fc receptor genes
      (disease susceptibility), complement C4d-bound erythrocytes (diagnosis or disease
      activity), CD27 plasma cells (disease activity), 'interferon signature' (disease
      activity), and anti-C1q antibodies (disease activity and organ involvement).
      SUMMARY: There is a longstanding and recently rejuvenated enthusiasm for
      biomarkers that precisely and specifically reflect the pathophysiologic and
      clinical changes in systemic lupus erythematosus. Promising candidate biomarkers
      have been identified but must still be validated through rigorous, large-scale
      multicenter studies.

PMID- 16093832
TI  - Rituximab anti-B-cell therapy in systemic lupus erythematosus: pointing to the
      future.
AB  - PURPOSE OF REVIEW: To discuss the clinical effects and the immunologic
      consequences of transient B-cell depletion using the anti-CD20 monoclonal
      antibody rituximab in systemic lupus erythematosus. RECENT FINDINGS: A total of
      100 rituximab-treated patients with severe disease, refractory to major
      immunosuppressive treatment, have been reported so far. Within a median follow-up
      period of 12 months rituximab was well tolerated, which is compatible with the
      experience accumulated from its use in more than 500 000 lymphoma patients. About
      80% of patients achieved marked and rapid reductions in global disease activity.
      Because of the clinical heterogeneity, dosing differences, and concomitant
      treatments, including cyclophosphamide in 35% of patients, a proper evaluation of
      the clinical efficacy or rituximab is difficult. Variable degrees of clinical
      benefit have been reported for all clinical systemic lupus erythematosus
      manifestations, including active proliferative nephritis. Whereas 4-weekly
      infusions of 375 mg/m of rituximab result in complete B-cell depletion lasting
      most often from 3 to 8 months, a prolonged depletion does not always correlate
      with a more favorable clinical response. Total immunoglobulin levels and
      protective antibodies are preserved, but anti-dsDNA antibody titers decrease,
      often independently of the clinical response. SUMMARY: The findings reviewed
      point to a growing optimism for targeting B cells in the treatment of systemic
      lupus erythematosus; therefore double-blind studies comparing rituximab with
      existing immunosuppressive therapies are needed. Moreover, careful assessments of
      the effects of transient B-cell depletion on distinct autoimmune pathogenetic
      processes will enable optimization of therapeutic single or combined therapeutic
      schemes.

PMID- 16093833
TI  - Immunopathogenesis of primary Sjogren's syndrome: implications for disease
      management and therapy.
AB  - PURPOSE OF REVIEW: Recent studies have broadened our understanding of the
      etiopathogenesis and immunopathology of primary Sjogren's syndrome. This review
      highlights recent advances in understanding the underlying mechanisms of the
      disease as well as their implications for clinical handling and therapeutic
      options. RECENT FINDINGS: It becomes increasingly apparent that certain
      disturbances of the immune system (i.e. B-cell hyperreactivity and enhanced
      levels of B-cell-activating factor/B-lymphocyte stimulator) play a central role
      in this entity. Whether this is a primary abnormality or the result of
      predisposing factors or infectious, e.g. viral, agents remains uncertain. New
      insights into the pathogenesis also provide candidates for better diagnosis and
      classification of disease severity, such as flow cytometric analysis, measurement
      of soluble cell surface molecules, autoantibodies, cytokines, and ligands (B-cell
      activating factor/B-lymphocyte stimulator). Whether B-cell-directed therapies
      (i.e. blocking B-cell-activating factor/B-lymphocyte stimulator, anti-CD20
      therapy) will have an impact on primary Sjogren's syndrome needs to be shown in
      clinical trials. Alternative therapeutic approaches such as organ-targeted gene
      transfer are in development but must be carefully evaluated for safety and
      efficacy in preclinical models that resemble human primary Sjogren's syndrome.
      SUMMARY: The pathogenesis of primary Sjogren's syndrome is complex and the
      factors initiating and driving autoimmunity in this entity are largely unknown.
      Recent studies provide new insights into potential pathogenetic mechanisms of the
      disease and, thereby, the chance for improved strategies in disease management
      and therapy.

PMID- 16093834
TI  - Pediatric and heritable disorders.

PMID- 16093835
TI  - Outcome in juvenile onset systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: Over the past 2 decades, there has been a marked improvement
      in survival among patients with juvenile-onset systemic lupus erythematosus. As a
      result of the increased life expectancy, children and adolescents with systemic
      lupus erythematosus are now faced with considerable morbidity resulting from
      sequelae of disease activity, side effects of medications, and comorbid
      conditions. This morbidity affects physical and psychosocial well-being.
      Therefore, the need is increasing for monitoring the development of irreversible
      organ damage and the effect of the disease and its treatment on daily life. This
      review summarizes the recent advances in the investigation on survival,
      accumulated damage, and health-related quality of life in patients with juvenile
      onset systemic lupus erythematosus. RECENT FINDINGS: The 5-year survival rate of
      patients with juvenile-onset systemic lupus erythematosus approaches 100%, and
      the 10-year survival rate is close to 90%. The development of cumulative organ
      damage has been observed in 50-60% of patients. Children and adolescents with
      systemic lupus erythematosus have been found to have poorer health-related
      quality of life, particularly in the physical domain, and lower socioeconomic
      achievements than their healthy peers. SUMMARY: The prolongation of the life span
      of patients with juvenile-onset systemic lupus erythematosus has been accompanied
      by a substantial risk of damage accumulation and has not been paralleled by an
      improvement in health-related quality of life. This problem highlights the need
      of measuring cumulative organ damage and health-related quality of life in the
      long-term follow-up of patients with juvenile-onset systemic lupus erythematosus
      and of designing new treatments and treatment strategies that are aimed not only
      at improving control of disease activity but also at minimizing the development
      of nonreversible damage.

PMID- 16093836
TI  - Imaging in juvenile arthritis.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight recent developments
      in imaging in juvenile arthritis. RECENT FINDINGS: The developments in imaging in
      juvenile arthritis are primarily focused on evaluation of destructive changes and
      inflammatory changes in joints. Plain radiography can demonstrate destructive
      changes in juvenile arthritis. The most validated instrument for assessing
      destructive changes juvenile arthritis is the Poznanski index, and this index is
      being used more in studies to understand the natural history and clinical
      correlates of destructive disease. Magnetic resonance imaging has been shown to
      be superior to plain radiography in demonstrating destructive changes. Further
      work is proceeding to detect earlier, biochemical changes in articular cartilage
      prior to the development of thinning or erosion. Magnetic resonance imaging and
      ultrasound can demonstrate both inflammatory and destructive changes. Utilization
      of these techniques to show inflammatory changes can provide information about
      joints that can supplement physical examination, particularly in difficult joints
      to examine, such as the hips, temporomandibular joints, small joints of the feet,
      and tenosynovial locations. This information may help to guide therapy. SUMMARY:
      Imaging provides useful information to supplement clinical and laboratory
      examination in the optimal treatment of patients with juvenile arthritis.

PMID- 16093837
TI  - Caspase recruitment domain 15 mutations and rheumatic diseases.
AB  - PURPOSE OF REVIEW: The purpose of this article is to review the foundational work
      and current developments on a group of rheumatic disorders associated with
      mutations in the caspase recruitment domain 15/nucleotide oligomerization domain
      2 gene. RECENT FINDINGS: To date, there are at least 10 arthritic conditions for
      which specific genetic mutations have been demonstrated. They include familial
      Mediterranean fever; tumor necrosis factor receptor associated periodic syndrome;
      hyper immunoglobulin D syndrome; neonatal onset multisystemic inflammatory
      disease; pyogenic arthritis pyoderma gangrenosum and acne; Muckle-Wells syndrome;
      familial cold autoinflammatory syndrome; immunodysregulation, polyendocrinopathy,
      enteropathy, X-linked syndrome; Crohn's disease; and familial and sporadic
      sarcoid granulomatous arthritis. This review focuses on recent progress in the
      last two diseases and the caspase recruitment domain 15 genetic defects with
      which they are associated. Up to 50% of patients with familial granulomatous
      arthritis (Blau's syndrome), 90% of those with sporadic granulomatous arthritis
      (early-onset sarcoidosis), and 40% of individuals with Crohn's disease have
      documented mutations in the caspase recruitment domain 15 gene. SUMMARY: Although
      histologically, Crohn's disease and familial and sporadic sarcoid granulomatous
      arthritis are distinct from rheumatoid arthritis because of the defining presence
      (albeit in not all cases) of non-caseating granulomata in the synovial and
      intestinal tissues, respectively, they still represent a promising model of both
      chronic synovitis and uveitis. In addition, once the actual mechanism is
      discovered by which defects of the caspase recruitment domain 15 gene product
      lead to chronic arthritis, it may uncover unsuspected biologic targets for
      therapeutics.

PMID- 16093838
TI  - Familial autoinflammatory diseases: genetics, pathogenesis and treatment.
AB  - PURPOSE OF REVIEW: The systemic autoinflammatory diseases are characterized by
      seemingly unprovoked inflammation, without major involvement of the adaptive
      immune system. This review focuses mainly on a subset of these illnesses, the
      hereditary recurrent fevers, which include familial Mediterranean fever, the
      tumor necrosis factor receptor-associated periodic syndrome, the
      hyperimmunoglobulinemia D with periodic fever syndrome, and cryopyrin-associated
      periodic syndromes. This review elucidates how recent advances have impacted
      diagnosis, pathogenesis, and treatment. RECENT FINDINGS: More than 170 mutations
      have been identified in the four genes underlying the six hereditary recurrent
      fevers. Genetic testing has broadened the clinical and geographic boundaries of
      these illnesses, given rise to the concept of the cryopyrin-associated periodic
      syndromes as a disease spectrum, and permitted diagnosis of compound
      heterozygotes for mutations in two different hereditary recurrent fever genes.
      Genetics has also advanced our understanding of amyloidosis, a complication of
      the hereditary recurrent fevers, and suggested a possible role for common
      hereditary recurrent fever variants in other inflammatory conditions. Recent
      advances in molecular pathophysiology include the elucidation of the N-terminal
      PYRIN domain in protein-protein interactions, the description of the NALP3
      (cryopyrin) inflammasome as a macromolecular complex for interleukin-1beta
      activation, and the identification of signaling defects other than defective
      receptor shedding in patients with tumor necrosis factor receptor-associated
      periodic syndrome. These molecular insights form the conceptual basis for
      targeted biologic therapies. SUMMARY: Advances in molecular genetics extend our
      ability to recognize and treat patients with systemic autoinflammatory diseases
      and inform our understanding of the regulation of innate immunity in humans.

PMID- 16093839
TI  - Recent developments in immunomodulatory peptides in juvenile rheumatic diseases:
      from trigger to dimmer?
AB  - PURPOSE OF REVIEW: Current therapy for juvenile rheumatic diseases is based on
      general immune suppression or blocking inflammatory pathways. These treatments do
      not induce long-term disease remission and have a risk of side effects; this is
      especially unfavorable in children. It is better to focus on induction of
      tolerance mechanisms than on suppression of inflammation. This promotes epitope
      specific immunotherapy as a possible safe treatment option. RECENT FINDINGS: In
      the search for specific peptides for immunotherapy in autoimmunity, the focus is
      shifting from purported triggers of disease to peptides that regulate the ongoing
      inflammation. These so-called 'immunomodulatory peptides' are important in every
      healthy immune system. Several juvenile rheumatic diseases have been linked to
      certain immunomodulatory peptides. In juvenile dermatomyositis, peptides from
      human skeletal myosin play a role in the perpetuation of the disease. In systemic
      lupus erythematosus, the focus is mostly on DNA-derived peptides and peptides
      from anti-DNA antibodies. In juvenile idiopathic arthritis, heat shock proteins
      have been shown to contain important immunomodulatory epitopes. SUMMARY:
      Immunomodulatory peptides play an important role in juvenile rheumatic diseases.
      Promising candidates for immunotherapy have been identified. This opens the
      possibility of clinical testing in rheumatic diseases of childhood.

PMID- 16093840
TI  - Gene expression profiling in pediatric rheumatic disease: what have we learned?
      What can we learn?
AB  - PURPOSE OF THIS REVIEW: Gene expression profiling is emerging as a promising
      methodology in pediatric rheumatology research. There is considerable interest in
      using this technology as the basis for diagnostic assays. This review will
      summarize the new knowledge. RECENT FINDINGS: Most gene expression studies of
      children have been exploratory in nature. However, preliminary gene expression
      studies in juvenile dermatomyositis, systemic lupus erythematosus, and chronic
      forms of arthritis demonstrate both the promise and limits of this technology. It
      seems likely that gene expression profiling will significantly enhance our
      understanding of the immunopathology of childhood-onset rheumatic diseases;
      however, considerable impediments must be overcome before these assays move into
      the clinical arena. SUMMARY: Gene expression profiling carries considerable
      potential to provide novel insights into the rheumatic diseases of childhood.
      Future developments will determine whether these technologies provide new
      clinical diagnostic or prognostic tools.

PMID- 16093841
TI  - Update on the pathogenesis and treatment of systemic onset juvenile rheumatoid
      arthritis.
AB  - PURPOSE OF REVIEW: Although systemic onset juvenile rheumatoid arthritis accounts
      for only about 20% of most reported series, children with systemic onset juvenile
      rheumatoid arthritis are often the most difficult to treat. Many children with
      persistent systemic onset juvenile rheumatoid arthritis have marked physical and
      emotional disability as a result of both disease and treatment-related
      morbidities. This review highlights recent studies that better elucidate the
      etiopathogenesis of systemic onset juvenile rheumatoid arthritis. New therapies
      derived from better understanding of cytokines, cytokine gene expression, and
      their complex interactions, which result in inflammation, are improving our
      ability to control active disease while reducing or reliance on corticosteroids.
      RECENT FINDINGS: Recent advances in our understanding of the etiopathogenesis of
      systemic onset juvenile rheumatoid arthritis have led to therapies that
      specifically target the cytokines found in abnormal quantities in children with
      active disease. Biologic agents that directly target interleukin-1a, interleukin
      6, and tumor necrosis factor alpha are currently in use, and additional agents
      that modulate interleukin-18, myeloid-related proteins 8 and 14, natural killer
      cell function, and macrophage migration inhibitory factor production are under
      investigation. SUMMARY: Anakinra, monoclonal antibody to interleukin-6 receptor,
      and thalidomide each have led to significant clinical improvement with fewer side
      effects than resulted when corticosteroids were the mainstay of therapy.

PMID- 16093842
TI  - Pathogenesis and treatment of Kawasaki's disease.
AB  - PURPOSE OF REVIEW: Coronary artery damage resulting from Kawasaki's disease is
      the leading cause of acquired heart disease in children in the developed world.
      This review highlights advances in our understanding of the etiology of
      Kawasaki's disease, the immune response leading to vascular damage, potential
      biomarkers, and insights into mechanisms of disease addressed by an animal model.
      Clinical dilemmas are discussed in the context of the new American Heart
      Association recommendations for the diagnosis and treatment of Kawasaki's
      disease. RECENT FINDINGS: Improved understanding of the mechanisms of disease
      will assist in identifying predisposed individuals and in development of more
      effective therapy. Most investigators agree that an infectious trigger leads to
      massive activation of the immune system, resulting in a prolonged self-directed
      immune response at the coronary arteries. The etiology debate has centered on the
      nature of and mechanisms involved in immune activation. Genetic studies have not
      provided conclusive answers to these questions. Mechanistic studies done in
      animal models have pointed to specific biologic factors critical for coronary
      artery damage and together with studies in children may lead to more rationally
      conceived biologically based interventions. Increasingly, the questions regarding
      clinical management address timing of therapy and the management of children
      presenting with atypical Kawasaki's disease. New guidelines and management
      algorithms have been proposed by the American Heart Association to address these
      concerns. SUMMARY: Biochemical and phenotypic characterization of Kawasaki's
      disease continues to improve. Answers are closer on etiology, reliable
      biomarkers, valid predictors of coronary outcome, and improved treatment of this
      syndrome.

PMID- 16093843
TI  - The sources of pain in knee osteoarthritis.
AB  - PURPOSE OF REVIEW: To review the mechanisms for the production of pain in knee
      osteoarthritis. RECENT FINDINGS: Nociception is produced by stimulation of
      unmyelinated and small myelinated fibers in the joint and surrounding tissue. To
      produce pain, the stimuli must be either repeated or spatially clustered. When
      they reach the spinal cord, stimuli are subject to two inhibitory effectors:
      interneurons and descending central neurons. Inflammation lowers the threshold
      for nociception. In the joint, tissues containing nociceptors include primarily
      the joint capsule, ligaments, synovium, bone, and in the knee, the outer edge of
      the menisci. Nociceptive stimuli are likely to emanate from one or more of these
      locations in people with knee pain. This review does not cover psychological
      aspects of pain. SUMMARY: Nociception in the knee is complex, and the nociceptive
      stimuli are related to but fundamentally different from those producing cartilage
      loss. Better appreciation for these processes will facilitate the development of
      new treatments.

PMID- 16093844
TI  - Polymorphism in signal transduction is a major route through which osteoarthritis
      susceptibility is acting.
AB  - PURPOSE OF REVIEW: In the last year there has been considerable success in the
      identification of genes harbouring susceptibility for primary osteoarthritis.
      This report brings the reader up-to-date by focusing on three of the more
      compelling finds. RECENT FINDINGS: A UK group reported an association of the FRZB
      gene with hip osteoarthritis in females. FRZB codes for secreted frizzled-related
      protein 3, an antagonist of Wnt signalling. The Wnt signal transduction pathway
      is critical for normal development and is also active in adult tissues. Secreted
      frizzled-related protein 3 helps to maintain articular cartilage and the
      associated alleles at FRZB reduce the activity of this important protein. A
      Japanese group has reported an association of the asporin gene ASPN with knee and
      hip osteoarthritis and an association of the calmodulin 1 gene CALM1 with hip
      osteoarthritis. Asporin is a cartilage extracellular protein that regulates the
      activity of transforming growth factor-beta. Calmodulin is an intracellular
      protein that interacts with a number of proteins involved in signal transduction.
      The associated alleles at ASPN and CALM1 reduce the ability of chondrocytes to
      express the genes encoding aggrecan and type II collagen. Since these are
      essential structural components of articular cartilage, the ASPN and CALM1
      associations are predicted to adversely affect the maintenance of cartilage.
      SUMMARY: The FRZB, ASPN and CALM1 results are compelling and highlight that
      polymorphism in signal transduction pathways is a major component of
      osteoarthritis susceptibility. This is an exciting observation since signal
      transduction pathways are malleable and therefore potentially amenable to
      intervention and modification.

PMID- 16093845
TI  - Exercise as a treatment for osteoarthritis.
AB  - PURPOSE OF REVIEW: This review highlights recent important research, future
      directions, and clinical applications for exercise and osteoarthritis. It focuses
      on knee osteoarthritis because of its prevalence and the dearth of research
      involving other joint osteoarthritis. The review covers exercise prescription for
      symptomatic relief, and its potential role in reducing development and slowing
      progression of osteoarthritis. RECENT FINDINGS: Meta-analyses support
      recommendations that exercise is important in osteoarthritis management. Benefits
      appear to be additive when exercise is delivered with other interventions such as
      weight loss. Mode of exercise delivery has cost implications and may influence
      overall outcome. It appears that supervised exercise sessions are superior to
      home exercises for pain reduction. The challenge remains to increase the
      proportion of patients exercising. Areas of emerging interest are exercise to
      prevent disease or slow its progression and recognition of patient subgroups that
      may respond differently to treatment. Based on studies showing a relation between
      weaker quadriceps strength and increased risk of developing knee osteoarthritis,
      particularly in women, strength training may be able to prevent knee
      osteoarthritis. Novel exercise programs that strengthen hip muscles or alter
      impairments in knee neuromuscular control may also influence disease progression.
      SUMMARY: Future studies must identify cost-effective exercise modes, strategies
      to maximize exercise compliance and optimal treatment combinations. The role of
      muscle strength and altered neuromuscular control in the prevention and
      development of osteoarthritis must be evaluated with the view to devising and
      testing novel exercise interventions.

PMID- 16093846
TI  - Biomarkers in osteoarthritis.
AB  - PURPOSE OF REVIEW: Biomarker discovery and validation for osteoarthritis have
      accelerated over the past several years, coincident with an evolving
      understanding of joint tissue molecules and their complex interactions, and the
      compelling need for improved osteoarthritis outcome measures in clinical trials.
      This review highlights advances in osteoarthritis-related biomarker research
      within the past year. RECENT FINDINGS: The studies in the past year involving
      biochemical markers in humans can be assigned to one of four categories: new
      approaches and new biomarkers, exploratory studies in specialized disease
      subsets, large cross-sectional validation studies, and longitudinal studies, with
      and without an intervention. SUMMARY: Most these studies have examined the
      association of a biomarker with some aspect of the natural history of
      osteoarthritis. As illustrated by the six studies reviewed here that included
      therapeutic interventions, however, several biomarkers are emerging that display
      credible association with disease modification. The expanding pool of informative
      osteoarthritis-related biomarkers is expected to positively impact the
      development of therapeutics for this disease and, it is hoped, ultimately
      clinical care.

PMID- 16093847
TI  - Nutritional factors and osteoarthritis: recent developments.
AB  - PURPOSE OF REVIEW: The role of nutrition and nutritional supplements in the
      development and progression of osteoarthritis is now a topic of considerable
      public, industry, and academic interest. This review focuses on how the evidence
      for a role of nutritional factors or nutritional supplements in the management of
      knee osteoarthritis has been changed by recent research. RECENT FINDINGS: Recent
      studies include clinical trials of weight loss and exercise as interventions for
      osteoarthritis of the knee, the elucidation of mechanisms of oxidative stress on
      the chondrocyte genome, further study of vitamin C supplementation in an animal
      with spontaneous osteoarthritis, and further clinical and pharmacodynamic
      evaluations of glucosamine and chondroitin sulfate. Perplexing findings among
      these studies include the deleterious effects of vitamin C on osteoarthritis in
      the Hartley guinea pig, the low levels of glucosamine achieved in serum after an
      oral dose, recent negative clinical studies of glucosamine, and the heterogeneity
      of results among glucosamine trials. SUMMARY: With an intensification of research
      in this field come new clinical and basic science data, sometimes with surprising
      results. These confirm the considerable potential for a role of nutritional
      interventions for osteoarthritis, but they emphasize the need for systematic
      scientific evaluation of the claims made for such products.

PMID- 16093848
TI  - Footwear alterations and bracing as treatments for knee osteoarthritis.
AB  - PURPOSE OF REVIEW: The biomechanical aspects of gait and the impact of alignment
      have been recognized as important in the development and progression of knee
      osteoarthritis. Improving malalignment and altering the dynamic forces on the
      involved compartment of the knee during gait have the potential to improve the
      symptoms of knee osteoarthritis. This review examines the use of foot orthoses
      and knee braces to change the biomechanical forces on the knee joint and to
      reduce pain and improve function in patients with existing symptomatic knee
      osteoarthritis. RECENT FINDINGS: Malalignment has been shown to have an impact on
      the development and progression of knee osteoarthritis. Patients with medial
      compartment knee osteoarthritis who have a visible varus thrust will also
      progress at a more rapid rate than patients without a varus thrust. Lateral wedge
      foot orthoses have been shown in biomechanical studies and clinical studies to
      reduce the load on the medial compartment and improve the symptoms of medial
      compartment knee osteoarthritis. Knee braces that stabilize the knee joint and
      provide a valgus stress have been shown to improve pain and function in patients
      with medial compartment knee osteoarthritis. SUMMARY: The development of
      symptomatic knee osteoarthritis and the progression of joint space loss is in
      part a biomechanical process. To improve patients' function and possibly reduce
      disease progression, a biomechanical approach should be included in the treatment
      plan for patients with knee osteoarthritis. Foot orthoses and knee braces have
      been shown in selected patients to have a role in the management of
      unicompartmental knee osteoarthritis.

PMID- 16093849
TI  - Bibliography. Current world literature.

PMID- 16093851
TI  - Predicting outcomes in renal cell carcinoma.
AB  - PURPOSE OF REVIEW: Renal cell carcinoma is estimated to account for more than
      35,000 new diagnoses and more than 12,000 cancer-related deaths in the United
      States in 2005, making it the most lethal of genitourinary malignancies.
      Approximately 25% of patients with renal cell carcinoma present with metastases,
      and about a third of those treated surgically for localized renal cell carcinoma
      will develop a recurrence. Current therapeutic options for disseminated disease
      benefit only a small percentage of patients. RECENT FINDINGS: Many clinical,
      histologic, and molecular factors have been identified that place a patient at
      risk for recurrence. Several prognostic algorithms, or nomograms, for renal cell
      carcinoma survival or recurrence after nephrectomy have been developed that
      incorporate many of these factors. SUMMARY: Renal cell carcinoma nomograms allow
      more accurate counseling of patients regarding their probable clinical course,
      facilitate treatment planning, and identify high-risk patients for experimental
      treatments.

PMID- 16093852
TI  - Renal tumor ablation.
AB  - PURPOSE OF REVIEW: The management of small renal tumors is changing from radical
      nephrectomy to nephron-conserving surgery. The aim of this review is to discuss
      the currently prevailing methods used for nonextirpative renal tumor ablation.
      The studies published in English during 2004 to May 2005 have been reviewed in
      this article. RECENT FINDINGS: Of the various ablation techniques, cryotherapy
      and radiofrequency ablation are being increasingly applied clinically. They can
      be performed either laparoscopically or percutaneously using a combination of
      fine probes and high-resolution imaging techniques for focusing and monitoring
      the therapy. Noninvasive tumor ablation by high-intensity focused ultrasound, and
      other techniques, is still at an experimental stage. SUMMARY: Although the
      initial outcomes of cryoablation and radiofrequency ablation are encouraging,
      long-term studies are necessary to confirm their lasting efficacy. The optimal
      modality for tumor targeting, monitoring therapy, and follow-up remains to be
      determined. These ablative techniques should be reserved for carefully selected
      patients, the data should be prospectively accrued, and the results should be
      compared to that of the reference standard, open or laparoscopic partial
      nephrectomy.

PMID- 16093853
TI  - Laparoscopic partial nephrectomy.
AB  - PURPOSE OF REVIEW: This review defines the current role, indications,
      contraindications, advances, complications, and outcomes of laparoscopic partial
      nephrectomy in the management of renal tumors. RECENT FINDINGS: Recent
      publications have widened the scope for the application of this technology. The
      new advances in the management of renal tumors and the tools for tumor excision,
      renal parenchymal reconstruction, hemostasis, renal vascular control to establish
      renal ischemia, and the ability to avoid positive surgical margins have made the
      procedure safe and feasible in the hands of an experienced laparoscopist.
      SUMMARY: The trend toward nephron-sparing surgery has become stronger even in the
      presence of normal contralateral functioning kidney. Data on oncologic efficacy
      are promising, and partial nephrectomy is becoming a standard therapy for renal
      tumors less than 4 cm in size in many centers. Laparoscopic partial nephrectomy
      has evolved significantly during the past 10 years in our experience as well as
      that of others. It cannot be considered as a standard yet, but it is being
      performed in rapidly increasing numbers with good surgical efficiency and
      oncologic efficacy parallel to that of open surgery.

PMID- 16093854
TI  - Is the use of anything but MVAC justified in the evidence-based medicine era?

PMID- 16093855
TI  - Current status of establishing standards for lymphadenectomy in the treatment of
      bladder cancer.
AB  - PURPOSE: Pelvic lymph node dissection at the time of radical cystectomy is a
      crucial component of the surgical management of invasive bladder cancer. No
      established therapeutic or diagnostic guidelines regarding pelvic lymph node
      dissection are, however, currently available. We reviewed the past and
      contemporary literature to clarify the current role of pelvic lymph node
      dissection both as a staging modality as well as potential therapeutic
      intervention. RECENT FINDINGS: The role of pelvic lymph node dissection has
      evolved over the past 60 years. Although the added benefits of radical cystectomy
      over simple cystectomy alone are accepted, an optimal template for pelvic lymph
      node dissection has not been established. Increasing evidence suggesting
      therapeutic and diagnostic benefits by extending the boundaries of
      lymphadenectomy or by increasing the number of nodes excised has been reported.
      Much of the recent literature, however, is based on retrospective studies, and is
      influenced by factors such as node count variability, inconsistencies in the
      quality of the surgery, and the biases in patient selection. Currently, the
      optimal boundaries of pelvic lymph node dissection and the minimum number of
      nodes to be pathologically examined remain undetermined. SUMMARY: The diagnostic
      and therapeutic benefits obtained by extending the limits of lymphadenectomy are
      compelling but inconclusive. Establishing standards for pelvic lymph node
      dissection will not only increase the consistency of staging and improve the
      design and interpretation of clinical trials in invasive bladder cancer but also
      help to identify and optimize the therapeutic benefits of lymphadenectomy.
      Prospective, randomized trials will be needed to properly establish the extent of
      lymphadenectomy required to obtain such benefits.

PMID- 16093856
TI  - Antisense oligonucleotide therapy in the management of bladder cancer.
AB  - PURPOSE OF REVIEW: In this paper, we will review the recent advances in antisense
      oligonucleotide therapy in the treatment of superficial bladder cancer. Bladder
      cancer has an exciting potential as a model to study antisense oligonucleotide
      therapy because of the ease of accessibility of treatment, ease of diagnosis
      through biopsy and urine cytology, and direct observation of treatment efficacy
      through cystoscopy and posttreatment biopsy. RECENT FINDINGS: We will elaborate
      on the recent developments in the delivery of antisense oligonucleotide and the
      implications of these results on the use of antisense oligonucleotide
      intravesically. We will also discuss recent preclinical in-vitro results of
      antisense oligonucleotide therapy in different bladder cancer cell lines.
      SUMMARY: Recent developments of the in-vitro and animal in-vivo effectiveness of
      antisense treatment in bladder cancer provide the foundation to pursue future
      phase I clinical trials. Antisense oligonucleotide technology is a promising tool
      that may become an effective method of treating bladder cancer.

PMID- 16093857
TI  - Impact of socioeconomic status on bladder cancer outcome.
AB  - PURPOSE OF REVIEW: To give an update on the possible influence of socioeconomic
      status on bladder cancer outcome. RECENT FINDINGS: Research to investigate the
      impact of socioeconomic status on bladder cancer outcome has increased during the
      past 2 years. The findings of these studies show that socioeconomic status is a
      significant predictor of survival in male and female patients presenting with
      bladder cancer, when death from all causes is considered. Very limited data on
      the effect of affluence on bladder cancer-specific survival, however, are
      available. Bladder cancer is the only common malignancy for which women have a
      worse prognosis than men. Recent evidence suggests that the finding of worse
      survival in women may be confined to those from more deprived areas. SUMMARY:
      Bladder cancer outcomes are directly influenced by social deprivation.

PMID- 16093858
TI  - Short- and long-term issues regarding urethral management in male radical
      cystectomy patients.
AB  - PURPOSE OF REVIEW: Radical cystectomy remains the gold-standard therapy for
      invasive bladder cancer. Management of the urethra before, during, and after
      cystectomy, however, is still not standardized. Herein, the rationale for
      different management algorithms is given. RECENT FINDINGS: The literature remains
      inconsistent regarding the best diagnostic and therapeutic management of the
      urethra before and during cystectomy as well as afterwards. The risk of urethral
      recurrence may in fact be lower after orthotopic urinary diversion, but the
      evidence for this and other recommendations comes from retrospective series.
      Urethral recurrence, although uncommon, continues to have a poor prognosis, and
      the optimal follow-up regimen is unclear. The importance of lifelong follow-up is
      unquestioned. SUMMARY: Risk factors for urethral involvement/recurrence can be
      determined before, during, and after radical cystectomy. The best way to diagnose
      and predict who will recur, however, is still unknown, as is the optimal follow
      up regimen and treatment for the remnant urethra. The type of urinary diversion
      may in fact influence disease recurrence, as it also affects possible therapy for
      patients with recurrence.

PMID- 16093859
TI  - Endoscopic and minimally invasive approaches to upper tract urothelial carcinoma.
AB  - PURPOSE OF REVIEW: In recent years, minimally invasive techniques have been
      widely applied to urologic diseases affecting the upper and lower urinary tracts.
      Technologic advances in both laparoscopy and endoscopy provide an opportunity to
      improve the treatment of urothelial carcinoma outside the bladder. We review the
      recent studies relevant to the therapy for urothelial cell carcinoma of the upper
      urinary tract. RECENT FINDINGS: Despite the availability of improved
      ureteroscopes and newer ablative energy sources, endoscopic management of upper
      tract urothelial tumors must be approached cautiously. Factors that increase the
      risk of recurrent or progressive disease include stage, grade, and size. Although
      percutaneous access permits larger instruments and may improve tumor resection,
      the outcome is determined by tumor characteristics. Adjuvant therapies, both
      systemic and local, are still lacking and require further study. Laparoscopic
      nephroureterectomy is clearly feasible and reduces patient morbidity. The limited
      data available suggest that oncologic outcomes of laparoscopic nephroureterectomy
      are comparable to the open operation, although longer follow-up is required. The
      optimal method of distal ureterectomy, ensuring complete removal of susceptible
      urothelium, remains to be determined. Adequate care must be taken during specimen
      retrieval to prevent tumor seeding or spillage. SUMMARY: Urologists currently
      have multiple tools to aid in the management of upper urinary tract urothelial
      tumors with minimal morbidity. Cancer-specific outcomes should, however, remain
      the primary concern and the development of novel systemic therapies needs to
      parallel the advances in surgical techniques.

PMID- 16093860
TI  - Recent developments in advanced urothelial cancer.
AB  - PURPOSE OF REVIEW: Metastatic or unresectable urothelial cancer of the urinary
      bladder has traditionally been treated with systemic chemotherapy, which is most
      often platinum-based. The long-term survival data and the associated toxicities
      from this form of therapy have spurred continuing interest in finding novel
      treatment options for this malignancy. RECENT FINDINGS: Recently, trials of new
      chemotherapy combinations, many incorporating platinum analogs or deleting
      platinum entirely, have been reported. None has yet been shown to be superior to
      cisplatin-based regimens. In addition, recent advances in imaging and laboratory
      technologies have provided new avenues to understand urothelial cancer behavior
      and prognosis. These advances provide optimism for improvements in the diagnosis,
      staging, and ultimately, selection of therapy for patients with urothelial
      cancer. SUMMARY: This review will summarize recent developments (circa 2004) in
      the diagnosis and management of advanced bladder cancer.

PMID- 16093861
TI  - What's new in the management of penile cancer?
AB  - PURPOSE OF REVIEW: Penile cancer is a rare disease. This has led to little in the
      way of therapeutic advances in the last two decades. Efforts have been made to
      minimize the use of disfiguring or morbid procedures in treating the primary
      tumor or managing the inguinal region. In addition, new insights have been gained
      into multimodal therapy for treating metastatic disease. We reviewed the
      literature published during the past two years to define the recent insights into
      the diagnosis and management of penile cancer. RECENT FINDINGS: Surveillance,
      Epidemiology and End Results Program data revealed poor outcome among African
      American patients compared with Caucasians with penile cancer. Risk factors,
      including human papilloma virus, HIV, and the practice of circumcision have been
      reassessed. To improve diagnosis and staging, new modifications in imaging have
      been developed including magnetic resonance imaging with artificial erection. In
      addition, the technique of dynamic sentinel node biopsy has been refined.
      Pathologic features of the primary tumor (i.e., stage, grade, vascular invasion)
      assist in identifying patients who would benefit from lymphadenectomy. Organ
      sparing treatments using laser ablation and reconstructive procedures to preserve
      glans or phallus length have also been developed. Systemic chemotherapy regimens,
      including consolidative approaches with surgery or radiotherapy, are discussed
      for advanced penile cancer. SUMMARY: Penile cancer remains a rare disease.
      Epidemiologic insights reveal provocative findings with respect to risk factors
      and racial differences in the outcome. Recent literature provides information
      that will aid urologists in (1) minimizing the need for disfiguring treatment of
      penile tumors in some patients and (2) reducing the number of unnecessary
      inguinal staging procedures in others. Novel systemic therapies that generate
      durable responses tested in multi-institutional treatment trials are needed.

PMID- 16093862
TI  - Bibliography. Current world literature.

PMID- 16093863
TI  - Eosinophils and gut dysmotility.

PMID- 16093864
TI  - Methotrexate for Crohn's disease: experience in a district general hospital.
AB  - Controlled trials have demonstrated the efficacy of methotrexate (MTX) in the
      induction and maintenance of remission in patients with luminal Crohn's disease,
      but its use outside of specialist centres remains limited. We present a case
      series of 24 patients treated with parenteral MTX in a district general hospital.
      Patients received an induction course of 25 mg weekly for 16 weeks, followed by
      maintenance doses of 15 mg weekly. Nineteen patients achieved remission during
      the induction period. Of these, 10 were maintained in remission for more than 12
      months. In total, there were six relapses within 1 year and five drug withdrawals
      due to side effects during the observation period. Of the six relapses, three
      required surgical intervention (with two of these re-starting methotrexate
      postoperatively) and three were recommenced on maintenance MTX after a short
      period at an increased dose. Our results are similar to outcomes achieved in
      large, randomized, controlled trials and indicate that MTX can be used safely and
      effectively for the treatment of refractory Crohn's disease in the district
      general hospital setting.

PMID- 16093865
TI  - Rationale and design of the REPEAT study: a phase III, randomized, clinical trial
      of peginterferon alfa-2a (40 kDa) plus ribavirin in non-responders to
      peginterferon alfa-2b (12 kDa) plus ribavirin.
AB  - OBJECTIVE: The REtreatment with PEgasys in pATients not responding to prior
      peginterferon alfa-2b (12 kDa)/ribavirin combination therapy (REPEAT) study is a
      phase III, randomized, parallel group, multinational clinical trial. The main
      objective is to compare the efficacy and safety of 48 and 72 weeks of treatment
      with peginterferon alfa-2a (40 kDa) (PEGASYS) plus ribavirin (COPEGUS) in
      patients who did not respond to previous peginterferon alfa-2b (12 kDa) plus
      ribavirin therapy. STUDY DESIGN: Patients will be randomized to one of four
      treatment groups: two groups will receive peginterferon alfa-2a (40 kDa) at the
      standard dose of 180 mug once weekly for 48 or 72 weeks. The other two groups
      will receive a 12-week high-dose induction regimen with peginterferon alfa-2a (40
      kDa) 360 mug once-weekly followed by 60 or 36 weeks of peginterferon alfa-2a (40
      kDa) 180 mug once weekly. All patients will receive the standard dose of
      ribavirin (1000 or 1200 mg/day) throughout treatment. The primary efficacy
      variable is the rate of sustained virological response, defined as non-detectable
      hepatitis C virus (HCV) RNA (<50 IU/ml) 24 weeks after the end of treatment.
      Secondary variables include the percentage of patients with non-detectable HCV
      RNA at the end of treatment, the percentage of patients with at least a 2-log10
      decrease in serum HCV RNA at weeks 12 and 24 of treatment, and the percentage of
      patients with non-detectable HCV RNA at treatment weeks 12, 24 and 48. Safety
      data will be recorded and analysed throughout the entire course of the study with
      the assistance of a Safety Review Board.

PMID- 16093866
TI  - 131I-Labelled-iodized oil for palliative treatment of hepatocellular carcinoma.
AB  - BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is growing in western
      countries. Poor liver status and tumour size make curative options scarce.
      Palliative treatments such as chemo-embolization are improving survival in
      selected patients, but side-effects are frequent. There is a need for the
      validation of alternative treatments. Metabolic radiotherapy using lipiodol
      labelled with 131I-iodine (I-131-lipiodol) is one of these treatments.
      OBJECTIVES: To analyse the effect of I-131-lipiodol in a population of advanced
      HCC patients and to define the potential prognostic factors in this setting.
      METHODS: A retrospective analysis of the effect of I-131-lipiodol on 29 patients
      bearing multifocal tumours was performed. An analysis of two subgroups, defined
      by a Cancer of the Liver Italian Program (CLIP) score of 2 or less (n=20) or
      greater than 2 (n=9) was performed to assess the prognostic significance of the
      score in this setting. RESULTS: Overall median survival in the entire study
      population was 203 days (95% confidence interval 83-322 days). Median survival
      was significantly better in the group with CLIP scores of 2 or less than in the
      group with CLIP scores greater than 2 (453 versus 60 days, P< or =0.001).
      Treatment-related mortality was 6.9% (one interstitial pneumonia and one acute
      liver failure). CONCLUSION: The survival of patients treated with I-131-lipiodol
      in this series compared favourably with published data. Stratification according
      to the CLIP score was useful to predict survival. In particular, patients with
      portal vein thrombosis should only be considered for I-131-lipiodol if the CLIP
      score is lower than 2.

PMID- 16093867
TI  - Intrafamilial spread of hepatitis B virus infection in Greece.
AB  - OBJECTIVE: No study has investigated the intrafamilial spread of hepatitis B
      virus (HBV) in Greece. We conducted a 9-year prospective study to determine the
      rate of HBV spread in family members when a member is identified as an HBV
      carrier, the possible routes and risk factors for transmission of HBV and the
      family members with the highest risk of infection according to kinship degrees.
      METHODS: A total of 387 family members of 166 hepatitis B surface antigen (HBsAg)
      carriers were investigated for the detection of HBV infection markers using
      standard enzyme immunoassays; 6.696 blood donors from the same area were used as
      controls. RESULTS: Serological markers of past or current HBV infection were
      detected significantly more frequently among family members of HBsAg carriers
      (23.2 and 15.8%, respectively) compared with blood donors (14.1 and 0.85%,
      respectively). The prevalence of the above markers was higher among siblings,
      husbands and parents of the carriers. Offspring of the female index cases had
      higher rates of current or past infection. HBV infection markers were
      significantly increased in family members who reported common use of syringes
      (P<0.001), birth in rural areas (P<0.001) and a low level of education (P<0.001).
      CONCLUSIONS: We demonstrated a high risk of HBV transmission among family members
      of HBsAg carriers, which was associated with special risk factors for contracting
      HBV. Our findings indicate the need for strict adherence to the universal
      guidelines of vaccination against HBV and also the need for an immediate
      investigation of other potentially infected relatives among family members of
      HBsAg carriers.

PMID- 16093868
TI  - The effect of taurine or betaine pretreatment on hepatotoxicity and prooxidant
      status induced by lipopolysaccharide treatment in the liver of rats.
AB  - BACKGROUND: Taurine or betaine have been reported to have antioxidative potential
      and inhibit Kupffer cell activation. These effects may play an important role in
      their hepatoprotective effects. Therefore, they may also have protective effects
      in lipopolysaccharide hepatotoxicity by both inhibiting Kupffer cell activation
      and behaving as antioxidants. DESIGN: The prophylactic efficiency of taurine or
      betaine pretreatment for the prevention of peroxidative changes induced by
      lipopolysaccharide treatment in the rat liver was investigated. METHODS:
      Lipopolysaccharide (10 mg/kg intraperitoneally) was given to rats pretreated with
      taurine (1.5%, w/v) or betaine (1.5%, w/v) in drinking water for 4 weeks and
      plasma transaminase activities as well as hepatic malondialdehyde, diene
      conjugate (DC), glutathione, alpha-tocopherol and ascorbic acid levels, and
      superoxide dismutase (SOD) and glutathione peroxidase activities were determined.
      RESULTS: Significant increases in plasma transaminase activities and hepatic
      malondialdehyde and DC levels and decreases in hepatic glutathione and alpha
      tocopherol levels and SOD and glutathione peroxidase activities were observed 6 h
      after lipopolysaccharide treatment. This treatment did not alter ascorbic acid
      levels in the liver compared with controls. Taurine or betaine pretreatment in
      lipopolysaccharide-injected rats caused significant decreases in plasma
      transaminase activities and hepatic malondialdehyde and DC levels, and
      significant increases in glutathione and alpha-tocopherol (not betaine) levels
      without changing ascorbic acid levels and SOD and glutathione peroxidase
      activities in the liver. CONCLUSIONS: Our findings clearly indicate that taurine
      or betaine pretreatment was effective in the prevention of lipopolysaccharide
      induced hepatotoxicity and prooxidant status.

PMID- 16093869
TI  - Serum leptin, soluble leptin receptor, free leptin index and bone mineral density
      in patients with primary biliary cirrhosis.
AB  - BACKGROUND/AIM: The pathophysiology of osteoporosis in chronic liver diseases is
      unknown. Recent data suggest that serum leptin is associated with bone mineral
      density (BMD). In animal studies leptin was found to be a potent inhibitor of
      bone formation. We investigated the relationship between serum leptin levels,
      soluble leptin receptor (sOB-R), free leptin index (FLI) and BMD in patients with
      primary biliary cirrhosis (PBC). PATIENTS AND METHODS: Ninety-four female
      patients with PBC were included in this study; 122 healthy women served as
      controls. Serum leptin levels were measured by radioimmunoassay, sOB-R by enzyme
      linked immunosorbent assay. BMD was measured by dual energy X-ray absorptiometry
      in the lumbar spine and femoral neck. RESULTS: Serum leptin was significantly
      lower in patients with PBC compared with healthy controls. No difference was
      found between the body mass index (BMI) of patients and controls. There was a
      strong positive correlation between leptin and BMI. In PBC no association was
      found between leptin, sOB-R and liver function tests, histological stages or the
      presence of osteoporosis. Osteoporosis was present in 38 patients. A positive
      correlation was found between serum leptin and femoral neck z-score even after
      adjustment for BMI, whereas serum sOB-R correlated inversely with the serum
      leptin level. There was no difference in FLI between the subgroups of PBC
      patients according to the stages of the disease. CONCLUSIONS: We found a lower
      serum leptin level and a higher sOB-R in patients with PBC, which could not be
      explained by the difference in BMI. As leptin was associated with BMD, it may be
      hypothesized that leptin is involved in the complex regulation of bone metabolism
      in PBC.

PMID- 16093870
TI  - Viridans group streptococci: an underestimated cause of spontaneous bacterial
      peritonitis in cirrhotic patients with ascites.
AB  - OBJECTIVES: The objective of the study was to examine the characteristics of
      spontaneous bacterial peritonitis (SBP) caused by streptococci, in particular
      viridans group streptococci (VGS), and to investigate a potential association
      between the long-term administration of norfloxacin and high-level resistance to
      fluoroquinolones in these organisms. METHODS: We reviewed 84 episodes of SBP and
      bacterascites caused by streptococci that occurred in 75 patients over a 6-year
      period. Isolates were tested for antibiotic susceptibility by the determination
      of minimum inhibitory concentrations. RESULTS: Of the 84 isolates, 46 (54.8%)
      were associated with SBP, 12 (14.3%) were associated with symptomatic
      bacterascites, and 26 (31%) were associated with asymptomatic bacterascites. VGS
      were responsible for 39 of the 58 episodes of SBP and symptomatic bacterascites,
      largely preceding group B streptococci (n=7), Streptococcus pneumoniae (n=6) and
      Streptococcus bovis (n=5). Most of the episodes were community acquired. An
      extraperitoneal site of infection was found in three patients only. Positive
      blood cultures were less frequent in patients with VGS infection than in those
      with SBP caused by other streptococci (12.8 versus 52.6%, P<0.001). The rates of
      susceptibility to penicillin, amoxicillin and cefotaxime were 84.5, 87.9 and
      91.4%, respectively. All isolates, including those from patients receiving
      norfloxacin, were susceptible to levofloxacin and moxifloxacin. CONCLUSIONS: VGS
      are an underestimated cause of SBP in patients with cirrhosis. Most isolates are
      susceptible to beta-lactam agents and new fluoroquinolones.

PMID- 16093871
TI  - Pantoprazole 20 mg on demand is effective in the long-term management of patients
      with mild gastro-oesophageal reflux disease.
AB  - A total of 536 patients with endoscopically confirmed GORD grade 0/I were
      included in this multicentre study. In the acute phase, patients were treated
      with pantoprazole 20 mg o.d. for 4 weeks to obtain symptom relief. Symptom-free
      patients were included in the subsequent long-term phase, and were randomly
      treated on demand with either pantoprazole 20 mg or placebo for 6 months
      (antacids as rescue medication). After the 4 weeks acute phase, 439 symptom-free
      patients entered the long-term phase. The perceived average daily symptom load
      remained significantly lower during the 6-month on-demand treatment with
      pantoprazole 20 mg as compared to placebo. Both the rates for unwillingness to
      continue and number of additional antacids taken were also significantly lower
      with pantoprazole 20 mg than with placebo. Hence, on-demand treatment with
      pantoprazole 20 mg is safe and effective in maintaining control of the symptoms
      heartburn, acid regurgitation and pain on swallowing symptoms in patients with
      GORD grade 0/I with superiority to placebo.

PMID- 16093872
TI  - Barrett's surveillance is worthwhile and detects curable cancers. A prospective
      cohort study addressing cancer incidence, treatment outcome and survival.
AB  - OBJECTIVES: To establish whether Barrett's surveillance is worthwhile in terms of
      incident cancers and whether outcomes are favourable. METHODS: A prospective non
      randomized single centre Barrett's surveillance programme commencing 1 January
      1992 through 1 April 2001 (112 months). Oesophagectomy recommended for high-grade
      dysplasia or carcinoma. RESULTS: Of 23 725 patients, 506 were diagnosed as
      Barrett's oesophagus and 24 (5%) had carcinoma at diagnosis (prevalence cancers).
      One hundred and twenty-six patients had at least one surveillance endoscopy; 248
      surveillance endoscopies were performed spanning 338 patient years. Thirteen
      surveillance (incidence) cancers were detected. In the prevalence cancer group 12
      of the 24 patients underwent oesophagectomy. Lymph nodes showed evidence of
      metastases in 10 of the 12 resections. In the surveillance group 10 patients
      underwent oesophagectomy. Lymph nodes showed evidence of metastases in one of the
      10 resections. One patient in the prevalence cancer group (4% of group; 8% of
      those operated) and seven patients in the surveillance cancer group (54% of
      group; 70% of those operated) remain disease-free more than 2 years post
      oesophagectomy. The cost per cancer cured is 7546 pounds. One curable cancer was
      detected per 48 patient years of surveillance. CONCLUSIONS: Few Barrett's
      surveillance studies have addressed treatment outcomes and survival. In our study
      5% of Barrett's patients undergoing endoscopy have prevalent cancers. If
      surveillance is performed, 4% per year develop cancer and 2% per year are cured
      of their cancers. Most surveillance cancers are operable and of those undergoing
      surgery 70% are cured. Barrett's surveillance is cost-effective compared with
      other cancer screening or surveillance initiatives.

PMID- 16093873
TI  - Bacillus clausii effect on gene expression pattern in small bowel mucosa using
      DNA microarray analysis.
AB  - BACKGROUND: Probiotics are widely used for the cure or prevention of several
      clinical conditions. However, clinical decisions need to be substantiated by an
      analysis of the complex bacteria-host interplay in the intestinal lumen. AIMS: To
      identify the gene expression pattern induced by Bacillus clausii in the
      intestinal mucosa of healthy individuals. METHODS: Six male patients (mean age
      38+/-5 years) affected by endoscopically confirmed mild oesophagitis were treated
      for one month with esomeprazole, and were randomly selected to receive or not B.
      clausii (groups I and II, respectively). Duodenal biopsies were taken pre and
      post-treatment to identify the modification of gene expression, using the
      GeneChip Human U133A array. To validate the microarray analysis, real-time
      reverse transcriptase-polymerase chain reaction (PCR) of five target genes was
      performed. RESULTS: After B. clausii administration, a total of 158 and 265 genes
      were up and downregulated, respectively. Quantitative PCR confirmed the
      microarray data. B. clausii mainly affected the expression of genes involved in
      immune response and inflammation, apoptosis and cell growth, cell
      differentiation, cell-cell signalling, cell adhesion, signal transcription and
      transduction. CONCLUSIONS: Our data represent the first global analysis of B.
      clausii effects on the gene expression profile in normal intestine, and provide
      the basis to identify the mechanisms by which these agents interact with the host
      and exert their beneficial effects. Future studies are needed to clarify the B.
      clausii-induced gene pattern in the clinical disorders in which probiotics have
      proved to be effective.

PMID- 16093874
TI  - Impact of bitter taste on gastric motility.
AB  - BACKGROUND: Unexplained nausea and vomiting is often associated with delayed
      gastric emptying in patients with functional dyspepsia. We hypothesized that the
      experience of an unpleasant, nauseating taste could lead to a delay in gastric
      emptying. METHODS: Sixteen healthy women consumed a bland liquid test meal on
      three separate study days. On two of the study days subjects sham fed either a
      bitter tasting, modified Slim-Fast bar or one with a pleasant strawberry flavour.
      The time for 50% gastric emptying (GE(50)) was non-invasively assessed by
      electrical impedance tomography and antral motility by electrogastrography (EGG).
      RESULTS: Gastric emptying was significantly delayed by sham feeding the bitter
      compared with the pleasant bar, GE(50) 24.7+/-3.9 versus 17.2+/-1.8 min, P<0.05.
      EGG power rose significantly during both the pleasant (basal 1.46+/-0.07 to
      2.33+/-0.14 log(10) microV(2)/min, P=0.000) and the bitter sham feed (basal
      1.64+/-0.09 to 2.35+/-0.11 log(10) microV(2)/min, P=0.000). CONCLUSION: An
      unpleasant bitter taste delays gastric emptying but does not significantly impair
      antral motility.

PMID- 16093875
TI  - Abdominal tuberculosis in Bradford, UK: 1992-2002.
AB  - INTRODUCTION: Bradford, in West Yorkshire, United Kingdom, has a population of
      486 340 of which 17.3% originate from South Asia. We describe our experience of
      abdominal tuberculosis over a 10 year period. METHODS: Fifty-nine cases of
      abdominal tuberculosis were identified between 1992 and 2002 from the
      Tuberculosis Registry, Bradford hospitals. Fifty case records were available for
      retrospective review. RESULTS: Median age of the patients was 38 years (range, 14
      81) and 35 (59.3%) were females. Fifty-four (91.5%) patients were of South Asian
      origin, four (6.8%) were Caucasians and one patient was an Arab. The mean
      standardized incidence of abdominal tuberculosis in the South Asian population
      during the study period was 9.32 cases/10(5)/year whereas in the local white
      population it was 0.1/10(5)/year (relative risk=93). Fever (90%), abdominal pain
      (88%) and weight loss (82%) were the commonest presenting features. Ileocaecal
      region in 20 (40%) patients and tubercular peritonitis in 16 (32%) cases were the
      common sites involved. Active pulmonary tuberculosis was present in 18 (36%)
      patients. Diagnosis of tuberculosis was confirmed by isolating acid-fast bacilli
      or by demonstrating caseating granulomas on biopsy in 36 (72%) cases. Acid-fast
      bacilli isolated in all the 29 (58%) cases were Mycobacterium tuberculosis and
      were sensitive to all standard anti-tubercular drugs except one patient who was
      resistant to isoniazid. CONCLUSION: Abdominal tuberculosis remains a common
      problem in a multicultural community in the United Kingdom with a varied
      presentation. High index of suspicion is required for early diagnosis. Most of
      the patients respond very well to standard anti-tubercular therapy and surgery is
      required only in a minority of cases. Drug resistant abdominal tuberculosis has
      not been a problem in this series.

PMID- 16093876
TI  - Non-antibiotic therapies for Helicobacter pylori infection.
AB  - Despite years of experience with Helicobacter pylori treatment, the ideal regimen
      for treating the infection has not been found. The most effective eradication
      treatment is the combination of a proton pump inhibitor with antibiotics, but 10
      20% of the patients fail to obtain eradication of the infection. Antibiotic
      resistance is a major factor affecting the outcome of treatment. Non-antibiotic
      therapies, including phytomedicines, probiotics, and antioxidants, have been
      increasingly investigated as potential alternatives for the treatment of H.
      pylori. In this article, we review the non-antibiotic therapies for H. pylori
      infection.

PMID- 16093877
TI  - Gastric motor dysfunction: is eosinophilic mural gastritis a causative factor?
AB  - Delayed gastric emptying caused either by gastric motor dysfunction or by
      gastroparesis is a profoundly debilitating disorder. When unresponsive to medical
      therapy, patients may undergo radical surgery including near-total gastro
      oesophageal, with varied symptomatic improvement. We describe two patients who
      presented with symptoms consistent with gastro-oesophageal reflux, unresponsive
      to medical management. After fundoplication both developed symptoms of profound
      gastric motor dysfunction and subsequently proceeded to near-total gastro
      oesophageal with symptomatic improvement. Histological examination of both
      excised gastric specimens revealed eosinophilic mural gastritis. To our
      knowledge, these are the first cases to demonstrate the association of mural
      eosinophilia and symptomatic gastric motor dysfunction. We propose that patients
      with gastric motor dysfunction, refractory to medical management, progress to
      laparoscopy and mural biopsy before gastrectomy. This would allow histological
      analysis of the gastric wall, and in the event of a positive finding of mural
      eosinophilic gastritis would allow a trial of medical therapy that could include
      an eosinophilic stabilizer such as the leukotriene D4 receptor antagonist
      montelukast or intravenous corticosteroid therapy, which may alleviate the
      symptoms.

PMID- 16093878
TI  - Sclerosing cholangitis secondary to hepatic artery ligation after abdominal
      trauma.
AB  - Several causes have been postulated as responsible for secondary sclerosing
      cholangitis (SSC), mainly in adults, and, although in very different situations,
      ischaemia seems to be one of the most important factors. The term 'ischaemic
      cholangitis' has been used as a collective label for all these ischaemia-induced
      bile duct lesions. The biliary epithelium is dependent on arterial blood flow,
      unlike the hepatic parenchyma, which receives a dual blood supply from the
      hepatic artery and the portal vein. This makes the biliary epithelium very
      susceptible to changes in arterial blood flow. We present one adolescent patient
      who developed SSC after abdominal trauma with hepatectomy and ligation of the
      right hepatic artery. Different factors could have helped in the development of
      SSC in our patient (septicaemia, bile duct destruction, cholecystectomy) but
      right hepatic artery ligation seems to be the most important aetiological factor
      in the development of secondary ischaemic cholangitis.

PMID- 16093879
TI  - Dislocation of the cervical oesophagus: a rare cause of oesophageal obstruction.
AB  - We describe a case of obstruction of the cervical oesophagus in which
      ultrasonography and computed tomography revealed characteristic dislocation of
      the cervical oesophagus and food impaction in a segmental canal. Although the
      patient presented with complete obstruction initially, spontaneous recovery of
      passage was achieved with conservative therapy. One recurrent episode was noted
      during her remaining life span. To our knowledge, no similar case has been
      described previously.

PMID- 16093880
TI  - Sonographic diagnosis of coeliac disease in a case with suspected acute liver
      failure.
AB  - Mild liver dysfunction occurs in patients with coeliac disease frequently, but
      severe liver diseases in combination with coeliac disease are rare. A 19-year-old
      woman was referred for evaluation for emergency liver transplantation with
      progressive jaundice and prolongation of prothrombin time. She had a history of
      non-bloody diarrhoea for 3 months and weight loss of 12 kg. At admission,
      abdominal ultrasound revealed liver enlargement with increased echogenicity and
      marked thickening of the circular folds of the small intestine, suggestive of
      coeliac disease. The diagnosis was confirmed by endoscopic biopsy from the second
      part of the duodenum. On a gluten-free diet the patient recovered within 1 week
      and remained in excellent health up to the present date. Liver tests normalized
      within 5 months and a repeat abdominal ultrasound after 20 months revealed a
      normal liver and small intestine. This case report suggests that coeliac disease
      should also be considered in patients with unexplained severe acute liver disease
      and that abdominal ultrasound may be a helpful step to obtain to the correct
      diagnosis.

PMID- 16093881
TI  - Is the quality of life always depressed in patients with chronic hepatitis C on
      antiviral therapy?

PMID- 16093882
TI  - Response to Dr Waldum's letter regarding 'Idiopathic gastric acid hypersecretion
      presenting as a diarrheal disorder and mimicking both Zollinger-Ellison syndrome
      and Crohn's disease'.

PMID- 16093883
TI  - Moving from research to practice.

PMID- 16093884
TI  - Measuring the culture of medical group practices.
AB  - OBJECTIVE: To develop an instrument that can be used to assess the organizational
      culture of medical group practices. DATA SOURCES AND STUDY SETTING: Study
      participants were primary care physicians in 267 medical group practices. The
      iterative process began in Minnesota and then expanded to practices in 21 other
      states. DATA COLLECTION METHODS: Practice culture statements were collected using
      questionnaires distributed at a national medical group practice meeting and
      mailed questionnaires sent to a broader set of participants identified by the
      Medical Group Management Association. STUDY DESIGN: Using a framework developed
      earlier, physicians in medical groups were asked to react to statements that
      described the basic assumptions and patterns of behavior characteristic of their
      practices. An iterative process involving over 500 physicians in 267 practices
      was used to identify and refine statements. Factor analysis was used to group the
      statements into cohesive cultural dimensions. PRINCIPAL FINDINGS: Thirty-nine
      statements correlated with nine cultural dimensions were identified and a test of
      this instrument found that it successfully identified differences in the cultures
      of medical groups. CONCLUSIONS: Although there is increasing agreement that the
      culture of medical group practices is one of the most important factors
      influencing the cost and quality of care, efforts to understand and manage these
      cultures have been hampered by the lack of a measurement instrument. This article
      presents an instrument that has broad face validity in the group practice field
      and successfully differentiates the cultures of different types of practices.

PMID- 16093885
TI  - Area Health Education Centers: strengths, challenges, and implications for
      Academic Health Science Center leaders.
AB  - Drawing from the results of an empirical study, we discuss the strengths and
      challenges of Area Health Education Centers in three domains-mission, programs,
      and organization--and highlight their implications for Academic Health Science
      Center leaders.

PMID- 16093886
TI  - Impact of nurses' job satisfaction on organizational trust.
AB  - The matter of organization trust is gaining widespread attention because its
      perceived value and its erosion. Rampant organizational change has reportedly
      left nurses feeling betrayed, stressed, and vulnerable. This case study
      identifies specific aspects of job satisfaction that contribute to organizational
      trust. Findings offer guidance to the manager intending to create a culture of
      trust and subsequently promote organizational effectiveness.

PMID- 16093887
TI  - Entrepreneurial propensity in health care: models and propositions for empirical
      research.
AB  - We maintain that entrepreneurial propensity is a focal construct in
      entrepreneurial research. We synthesize the literature to develop models
      depicting the antecedents and consequents of entrepreneurial propensity in a
      network of other constructs and variables of interest in the health care
      industry. We advance propositions for empirical investigation and validation of
      competing research models associated with entrepreneurial propensity. We conclude
      with a discussion of directions of future research.

PMID- 16093888
TI  - A pre-post comparison of service operational efficiency and patient satisfaction
      under open access scheduling.
AB  - Three benefits of Open Access scheduling are tested pre- and postimplementation.
      Open Access improved operational efficiency, decreased number of days between
      appointment scheduling and being seen by a physician, and allowed more patients
      to see their primary care physician. Finally, results indicated that there was no
      significant difference in patient satisfaction.

PMID- 16093889
TI  - Use of a validated model to evaluate the impact of the work environment on
      outcomes at a magnet hospital.
AB  - Using a structural model, we evaluated the impact of leadership, staff stability,
      resources, workload, work environment, and staff expertise on nurse-sensitive
      patient outcomes to determine elements that can be modified.

PMID- 16093890
TI  - Institutional forces in the acceptance of managed care practices by physicians.
AB  - We evaluated physicians' acceptance of managed care using data from Connecticut
      physicians. We grouped physicians' attitudinal responses on three dimensions and
      applied an institutional distance framework to evaluate factors that influence
      physicians' acceptance of managed care practices. Our results demonstrate the
      potency of institutional forces in affecting physician attitudes: health care
      organizations must more effectively integrate their values and beliefs with the
      physician community. The institutional distance theory evaluated in this article
      provides new information for policymakers and managers as gaining physician
      acceptance of certain practices is necessary to ongoing efforts to reform the
      health care system.

PMID- 16093891
TI  - Emergency department psychiatric consultation arrangements.
AB  - The effects of organizational and environmental factors on emergency department
      psychiatric consultation arrangements and the influence of arrangement on service
      effectiveness are examined. The findings have implications for health care
      researchers, administrators, and policymakers, encouraging further exploration
      into arrangement type and conditions that produce optimal patient and
      organizational outcomes.

PMID- 16093892
TI  - Transfer pricing in hospitals and efficiency of physicians: the case of
      anesthesia services.
AB  - The objective is to investigate theoretically and empirically how the efficiency
      of the physicians involved in anesthesia and surgery can be optimized by the
      introduction of transfer pricing for anesthesia services. The anesthesiology data
      of approximately 57,000 operations carried out at the University Hospital Hamburg
      Eppendorf (UKE) in Germany in the period from 2000 to 2002 are analyzed using
      parametric and non-parametric methods. The principal finding of the empirical
      analysis is that the efficiency of the physicians involved in anesthesia and
      surgery at the UKE improved after the introduction of transfer pricing.

PMID- 16093893
TI  - Prospective evaluation of a Bayesian model to predict organizational change.
AB  - This research examines a subjective Bayesian model's ability to predict
      organizational change outcomes and sustainability of those outcomes for project
      teams participating in a multi-organizational improvement collaborative.

PMID- 16093894
TI  - Toward the substitution of invasive electroencephalography in epilepsy surgery.
AB  - The authors compared the localization accuracy of interictal
      magnetoencephalography (MEG) with ictal and interictal invasive video
      electroencephalography (VEEG) in identifying the epileptogenic zone in epilepsy
      surgery candidates. Forty-one patients, 29 with temporal lobe epilepsy (TLE) and
      12 with extratemporal lobe epilepsy (ETLE), participated. Only patients with
      interictal changes during the MEG recordings were included. A comparison of the
      accuracy of invasive VEEG and MEG seizure zone identification was based on the
      degree of overlap between the location of the actual surgical resection and the
      zone identified by each method, and the success of surgery in reducing seizure
      activity. No statistical differences were observed between the accuracy of
      invasive VEEG and MEG in determining the location of the seizure zone across TLE
      and ETLE cases. Invasive VEEG and MEG localization judgments were correct in 54%
      and 56% of the cases, respectively. Separate group analyses suggested that MEG
      may be less beneficial relative to invasive VEEG in ETLE than TLE cases. MEG is
      of statistically equivalent accuracy to invasive VEEG, despite the fact that its
      use has not reached optimal conditions. The authors predict the replacement of
      the more invasive procedure with MEG in the near future for TLE cases, subsequent
      to the optimization of the conditions under which preoperative MEG is performed.

PMID- 16093895
TI  - Notched delta, phenotype, and Angelman syndrome.
AB  - The notched delta pattern is one of the characteristic EEG features found in
      Angelman syndrome patients. The purpose of this study was to evaluate the
      possibility of using the notched delta pattern as a detection tool for Angelman
      syndrome patients by analyzing its frequency in a tertiary care pediatric center,
      its specificity for Angelman syndrome, and the age at which it was observed. The
      authors performed a retrospective review of the video-EEG recordings of all the
      patients who had either the notched delta pattern or a phenotype consistent with
      Angelman syndrome. The notched delta was observed in 1.1% of all the EEGs
      performed. Its specificity for Angelman syndrome was evaluated at 38%. The
      youngest age at which it was noted was 14 months. The results indicate that the
      notched delta pattern is relatively rare, but more frequent than expected, and is
      easily recognizable. The pattern was observed not only in Angelman syndrome
      patients, but also in children with a spectrum of conditions wider than reported.
      It is a powerful detection tool for Angelman syndrome when correlated to a
      suggestive phenotype, and the association of these features should raise
      suspicion for Angelman syndrome in both infants and adults.

PMID- 16093896
TI  - QEEG changes during carotid clamping in carotid endarterectomy: spectral edge
      frequency parameters and relative band power parameters.
AB  - Intraoperative monitoring is needed to identify accurately those patients in need
      of a shunt during carotid endarterectomy. EEG can be used for this purpose, but
      there is no consensus on the variables to use. Using a database consisting of 149
      EEGs recorded from patients during carotid endarterectomy under isoflurane (n=61)
      or propofol (n=88) anesthesia and who did or did not receive a shunt, the authors
      investigated which of 16 derivations (common reference, Cz) and 12 parameters
      (relative and absolute powers and spectral edge frequencies [SEFs]) singly or in
      combination could best distinguish between the shunt and the nonshunt groups for
      the two anesthesia regimens. Receiver operating characteristic curves were used
      to select derivation/parameter combinations for three types of trend computation:
      (1) values of relative powers and SEFs during clamping (C) only, (2) clamp minus
      preclamp (baseline) differences (C-B), and (3) C-B differences in absolute
      logarithmic power (DeltalogP). For both anesthesia regimens, C-B computation
      distinguished best between the shunt and nonshunt groups. For isoflurane
      anesthesia, SEF parameters were the best, and for propofol anesthesia the
      relative power parameters. Discriminant analysis, in which additional
      derivation/parameter combinations were added, increased the discriminative power
      of the DeltalogP computation but not of the C or C-B computations. For isoflurane
      anesthesia, SEF 90% was the best single parameter for distinguishing between
      patients who did and did not need a shunt and the four best derivations were F3
      Cz, P4-Cz, C4-Cz, and F7-Cz. For the propofol anesthesia, the relative power (C
      or C-B computations) of the delta band was the best and the four best derivations
      were F8-Cz, T4-Cz, C4-Cz, and F4-Cz.

PMID- 16093897
TI  - Utilization and yield of EEG in the elderly population.
AB  - The EEG is a common test ordered in the elderly population for a variety of
      indications such as syncope, encephalopathic states, transient unresponsive
      episodes, and clinical seizures. The authors analyzed the spectrum of EEG
      abnormalities in a series of 300 homogenous elderly patients in the southern
      region of Ireland who were referred for the above indications. Generalized
      slowing was seen in 30.7% and focal abnormalities in 9% of records. Thirteen
      records demonstrated focal sharp waves and one record showed generalized
      epileptiform discharges. Two records with seizures were identified, both with
      nonconvulsive status epilepticus. The incidence of ECG abnormalities was high
      (23%). In patients referred for syncope, the incidence of EEG epileptiform
      abnormalities (sharp waves) was 3%, in contrast to previous reports of 49%. In
      patients older than 80 years (the "old old"), EEG abnormalities were more common.
      The yield of the EEG for common referrals such as syncope, encephalopathy, and
      transient unresponsiveness is low for focal abnormalities. Electrocardiographic
      abnormalities were common and should be identified and treated appropriately.

PMID- 16093898
TI  - Automated state analyses: proposed applications to neonatal neurointensive care.
AB  - The two principal challenges of neonatal physiologic monitoring device are: (1)
      the development of computational strategies that consider the rudimentary forms
      of neonatal sleep state especially for preterm infants and (2) any physiologic
      monitoring device for clinical applications in a neonatal intensive care setting
      must be small, portable, and user-friendly. Our multicenter neonatal sleep
      consortium has acquired more than 1,100 multihour EEG-sleep recordings on over
      370 neonates, ranging from 24 to 44 weeks gestation. Each recording was visually
      scored for state, arousals, movements, and rapid eye movements, which were used
      as templates when applying spectral analyses. The authors have defined a brain
      dysmaturity index to represent functional brain reorganization as the prenate
      matures to a full-term age; delayed or accelerated physiologic behaviors have
      been described for the preterm cohort when compared to the full-term group at the
      same postmenstrual age. Seven EEG-sleep measures comprise this index: quiet sleep
      percentage, sleep cycle length, rapid eye movements, arousals, spectral beta EEG
      energies, spectral EEG correlations, and a spectral measure of respiratory
      regularity. Linear and nonlinear computational algorithms are being developed to
      automate the computation of the dysmaturity index and to identify new feature
      types that correlate with dysmaturity. Automated neonatal sleep monitoring system
      can potentially improve neonatal neurointensive care by facilitating analyses of
      pervasive neonatal brain disorders expressed primarily as altered sleep state
      organization, and help predict altered developmental trajectories of children at
      higher risk for neurologic sequelae.

PMID- 16093899
TI  - Compensation of intraoperative transcranial motor-evoked potential monitoring by
      compound muscle action potential after peripheral nerve stimulation.
AB  - It is often difficult to evaluate the results of transcranial motor-evoked
      potential (TCMEP) monitoring in patients under general anesthesia because these
      results are strongly affected by anesthetics and muscle relaxants. To exclude
      effects of muscle relaxants on TCMEP, compound muscle action potential (CMAP) by
      supramaximum stimulation of the median nerve immediately after transcranial
      stimulation (300 to 600 V) was recorded in 70 neurosurgical operations. A
      relative amplitude index (RAI) was defined as the amplitude of TCMEP after the
      operative procedure divided by the amplitude of TCMEP before the operative
      procedure. The RAI was calculated and was compensated by the amplitude of CMAP in
      141 limbs. In 12 limbs of 7 patients with postoperatively progressed motor
      paresis, the compensated RAI was less than 0.2. The compensated RAI in all other
      129 limbs of 63 patients without postoperative motor palsy was more than 0.2.
      These results suggest that compensation of TCMEP monitoring by CMAP is an easy
      and accurate method for removing the effects of muscle relaxants in TCMEP.

PMID- 16093900
TI  - Brainstem hyperexcitability during cataplexy.
AB  - The exact cause of narcolepsy-cataplexy syndrome remains unclear; however, the
      recent discovery of hypocretin deficiency in the lateral hypothalamus of
      narcoleptic patients has increased our understanding of its etiology. The authors
      performed masseter reflex, tibial F response, and blink reflex excitability
      studies during and between attacks in a 66-year-old man with status
      cataplecticus. Masseter reflex and F responses were inhibited while the blink
      reflex R2 component was enhanced during attacks, suggesting either
      hyperexcitability or disinhibition of pontine and/or medullary interneurons but
      hypoexcitability of pontine and spinal motor neurons during cataplexy.

PMID- 16093901
TI  - Usefulness of p300 in subjective memory complaints: a prospective study.
AB  - The existing studies about the utility of P300 latency for diagnostically
      classifying patients in preclinical stages of dementia are cross-sectional rather
      than longitudinal in design, and their results are inconclusive. The authors
      investigated the P300 value in a series of patients with subjective memory
      complaints using a prospective design. The study was performed in a consecutive
      series of 116 outpatients with subjective memory complaints as the predominant
      symptom. P300 (auditory oddball task) was performed immediately after the first
      clinical evaluation, and at 12 and 24 months. Final cognitive syndrome diagnosis
      (mean follow-up period, 27.7 months) was then made by a neurologist who was
      blinded to the neurophysiologic results. Diagnosis at the end of follow-up was 30
      cases of normal cognition, 30 cases of mild cognitive impairment, 28 cases of
      dementia of Alzheimer's type (DAT), five cases of vascular dementia, and one case
      of frontotemporal dementia; 22 patients were lost to follow-up. P300 latency was
      significantly higher for the DAT group (analysis of variance: P=0.023) throughout
      the study. The diagnostic value of P300 latency at baseline examination for DAT
      had a sensitivity of 52.9% and a specificity of 76.9%; the odds ratio was 3.75
      (95% confidence interval, 1.23-11.41). Findings from the present study suggest
      that assessment of evoked related potentials may contribute to the early
      detection of DAT.

PMID- 16093902
TI  - Cardiovascular risk profile with the new immunosuppressive combinations after
      renal transplantation.
AB  - Cardiovascular disease remains the main cause of death among kidney transplant
      patients. Cardiovascular risk burden already present at the moment of
      transplantation is substantially worsened by chronic use of immunosuppressants.
      On the other hand, chronic allograft nephropathy, a clinical-pathological result
      of immunological and non-immunological damage of the graft, is the main cause of
      graft loss in the long-term. Among the non-immunological factors contributing to
      the development of chronic allograft nephropathy, cardiovascular risk factors
      also seem to play a role. In the present review, we analyse the impact of the
      different immunosuppressive medications on cardiovascular risk factors after
      renal transplantation, including renal function.

PMID- 16093903
TI  - New risk factors for atherosclerosis in hypertension: focus on the prothrombotic
      state and lipoprotein(a).
AB  - Although adequate control of blood pressure is of basic importance in
      cardiovascular prevention in hypertensive patients, correction of additional risk
      factors is an integral part of their management. In addition to classical risk
      factors, epidemiological research has identified a number of other conditions
      that might significantly contribute to cardiovascular risk in the general
      population and might achieve specific relevance in patients with high blood
      pressure. In fact, more than 20% of patients with premature cardiovascular events
      do not have any of the traditional risk factors and, although effective
      intervention on blood pressure and additional risk factors has significantly
      reduced cardiovascular morbidity and mortality, the contribution to stroke,
      coronary artery disease and renal failure is still unacceptably high. Evaluation
      of new risk factors may further expand our capacity to predict atherothrombotic
      events when these factors are included along with the traditional ones in the
      assessment of global cardiovascular risk in hypertensive patients. Because it
      could be anticipated that the role of these novel factors will become
      increasingly evident in the future, researchers with an interest in hypertension
      and physicians dealing with problems related to cardiovascular prevention should
      give them appropriate consideration. This review summarizes the basic biology and
      clinical evidence of two emerging risk factors that are reciprocally related and
      contribute to the development and progression of organ damage in hypertension:
      the prothrombotic state and lipoprotein(a).

PMID- 16093904
TI  - Parathyroid hormone and hypertension.

PMID- 16093905
TI  - Quality of life in hypertensive patients: does it matter and should we measure
      it?

PMID- 16093906
TI  - Is central nitric oxide essential in hypertension?

PMID- 16093907
TI  - Serum parathyroid hormone as a predictor of increase in systolic blood pressure
      in men.
AB  - BACKGROUND: In cross-sectional studies there appears to be a link between calcium
      metabolism and blood pressure, and most studies have found a positive association
      between serum parathyroid hormone (PTH) and hypertension. OBJECTIVE: To determine
      the prognostic value of serum PTH regarding a future increase in blood pressure.
      DESIGN: A prospective cohort study. SUBJECTS: A total of 1784 individuals who had
      measurements of PTH in serum samples from both the fourth (1994) and fifth (2001)
      Tromso studies, who did not use blood pressure medication during the observation
      period, and had serum calcium less than 2.61 mmol/l, were included. MAIN OUTCOME
      MEASURE: Delta blood pressure (blood pressure from 2001 minus blood pressure from
      1994). RESULTS: The mean delta systolic blood pressure in the men and women
      during these 7 years was 5.8 and 8.1 mmHg, respectively. In a sex-specific linear
      regression model correcting for age, body mass index (BMI), and smoking status,
      serum PTH from 1994 was a significant predictor of delta systolic blood pressure
      in men (P < 0.01), but not in women. The difference in delta systolic blood
      pressure between those in the highest and those in the lowest PTH quartile was
      3.5 mmHg. Similarly, delta serum PTH (serum PTH from 2001 minus serum PTH from
      1994) was a significant predictor of delta systolic blood pressure in men (P <
      0.05). CONCLUSIONS: Although these findings do not prove a causal relationship
      between PTH and blood pressure, it adds to the growing number of indications that
      PTH is involved in the development of hypertension.

PMID- 16093908
TI  - Blood pressure and body mass index in lean rural and semi-urban subjects in West
      Africa.
AB  - BACKGROUND: Blood pressure (BP) is positively related to body mass index (BMI) in
      persons of both Caucasian and African origin, but the precise nature of the
      relationship is unclear. OBJECTIVE: To study the relationship between BP and BMI
      in a lean African population. DESIGN: A community-based cross-sectional study.
      METHODS: The BMI and BP were measured in 362 men and 592 women aged 40-75 years
      living in Ashanti, Ghana. In total, 498 lived in semi-urban areas and 456 in
      rural villages. RESULTS: The BMI was higher among semi-urban women [23.1 kg/m
      (95% confidence interval (CI), 22.5 to 23.6)] than semi-urban men [20.9 kg/m (95%
      CI, 20.6 to 21.5)], rural men [19.5 kg/m (95% CI, 19.1 to 19.9)] and rural women
      [19.9 kg/m (95% CI, 19.5 to 20.3)]. For systolic BP in women older than 52 years
      and in semi-urban women, the relationship was non-linear. The slope of the line
      below the change point ("knot") was greater than that above it. There was no
      evidence of non-linearity in men. For diastolic BP only younger women had a
      significant "knot" point at 18 kg/m. Again, the slope of the line below the
      "knot" was greater than that above it. In men, however, there was also evidence
      of a "knot" in younger and rural men, with the slope of the line below the "knot"
      being less that that above it (unlike in women). CONCLUSIONS: The relationship
      between BP and BMI is not linear, and is possibly sigmoid, but this may vary
      between subgroups.

PMID- 16093909
TI  - Isolated uncontrolled hypertension at home and in the office among treated
      hypertensive patients from the J-HOME study.
AB  - OBJECTIVES: To evaluate the current status of blood pressure (BP) control as
      measured at home and in the office, as well as to clarify and compare the
      prevalence and characteristics of isolated uncontrolled hypertension as measured
      at home (home hypertension) and in the office (office hypertension). DESIGN: A
      cross-sectional study. SETTING: Primary care offices in Japan. PARTICIPANTS: A
      sample of 3400 patients with essential hypertension (mean age, 66 years; males,
      45%) receiving antihypertensive treatment. RESULTS: Overall, the mean home
      systolic BP (SBP)/diastolic BP (DBP) was 140/82 mmHg, and the mean office SBP/DBP
      was 143/81 mmHg. Of the 3400 subjects, 19% had controlled hypertension (home
      SBP/DBP < 135/85 mmHg and office SBP/DBP < 140/90 mmHg), 23% had isolated
      uncontrolled home hypertension (home SBP/DBP >/= 135/85 mmHg and office SBP/DBP <
      140/90 mmHg), 15% had isolated uncontrolled office hypertension (home SBP/DBP <
      135/85 mmHg and office SBP/DBP < 140/90 mmHg), and 43% had uncontrolled
      hypertension (home SBP/DBP >/= 135/85 mmHg and office SBP/DBP >/= 140/90 mmHg).
      Compared to controlled hypertension, factors associated with isolated
      uncontrolled home hypertension included obesity, relatively higher office SBP,
      habitual drinking, and the use of two or more prescribed antihypertensive drugs.
      Compared to uncontrolled hypertension, factors associated with isolated
      uncontrolled office hypertension included female gender, lower body mass index,
      and relatively lower office SBP. CONCLUSIONS: The use of all four, three of four,
      or all three predictive factors might be useful for the clinician to suspect
      isolated uncontrolled home or office hypertension.

PMID- 16093910
TI  - Prevalence, awareness, treatment and control of hypertension in Portugal: the PAP
      study.
AB  - BACKGROUND: The objective of this study was to estimate the prevalence and
      distribution of hypertension and to determine the status of hypertension
      awareness, treatment and control in the Portuguese adult population. METHODS:
      This study was conducted in 2003, and a multistage cluster sampling method was
      used to select a national representative sample. A total of 5023 adults, age 18
      90 years, were examined. Three blood pressure measurements were obtained by
      trained observers using an OMROM M4-I sphygmomanometer after a 5-min sitting
      rest. Information on the history of hypertension and the use of antihypertensive
      medications was obtained by use of a standard questionnaire. RESULTS:
      Hypertension was defined as a mean systolic blood pressure > or = 140 mmHg and/or
      diastolic blood pressure > or = 90 mmHg, or the use of antihypertensive
      medications. Overall, 42.1% of the Portuguese adult population aged 18-90 years,
      representing 3 311 830 people, had hypertension. The age-specific prevalence of
      hypertension in the three age groups studied--younger than 35 years, 35-64 years
      old and older than 64 years--was 26.2, 54.7 and 79% in men and 12.4, 41.1 and
      78.7% in women, respectively. Among hypertensive patients, only 46.1% were aware
      of their high blood pressure, 39.0% were taking antihypertensive medication and
      11.2% achieved blood pressure control (< 140/90 mmHg). CONCLUSIONS: Our results
      indicate that hypertension is highly prevalent in Portugal. The percentages of
      those with hypertension that are aware, treated and controlled are unacceptably
      low. These results underscore the urgent need to develop national strategies to
      improve prevention, detection and treatment of hypertension in Portugal.

PMID- 16093911
TI  - Hypertension and health-related quality of life: an epidemiological study in
      patients attending hospital clinics in China.
AB  - OBJECTIVE: To examine the relationship between hypertension and health-related
      quality of life in patients attending hospital clinics in China. DESIGN AND
      METHODS: A cross-sectional survey. Patients over the age of 35 years attending
      outpatient clinics in 18 hospitals of eight major cities of northern and southern
      China were interviewed between June and July, 1999. Trained fieldworkers
      completed questionnaires regarding demographics, hypertension knowledge and
      awareness, treatment history and quality of life issues. Qualified physicians
      performed blood pressure assessments. RESULTS: A total of 9703 volunteers were
      enrolled; 4510 (46.5%) had hypertension. The results showed that hypertensive
      subjects scored lower in the multiple linear regression analyses in most
      questions on the quality of life questionnaire than those without hypertension
      after controlling for age, sex, sociodemographic factors, and co-morbidity. There
      was a strikingly high prevalence of physical complaints or symptoms. Among the
      variables considered, age, sex, hypertension, body mass index, educational level,
      smoking, history of cholesterol, family history of cardiovascular diseases and
      history of diabetes were statistically significantly correlated with health
      related quality of life. Subjects aware of having high blood pressure had a lower
      health-related quality of life score than subjects with high blood pressure but
      unaware of the diagnosis. Among treated subjects, those with controlled
      hypertension had higher health-related quality of life scores than those with
      poorly controlled hypertension. CONCLUSIONS: Hypertensive individuals represent a
      vulnerable population that merits special attention from healthcare providers and
      systems. This is especially important given that low health-related quality of
      life can be a risk factor for subsequent cardiovascular events or complications.

PMID- 16093912
TI  - High circulating levels of endogenous ouabain in the offspring of hypertensive
      and normotensive individuals.
AB  - OBJECTIVE: Impaired diastolic function and left ventricular hypertrophy can occur
      early in the natural history of essential hypertension. High circulating levels
      of endogenous ouabain (EO) have been described in essential hypertension and have
      also been associated with left ventricular hypertrophy. The aim of this study was
      to investigate whether these cardiac modifications are related to plasma EO
      levels in the offspring of hypertensive families. METHODS: The study involved 41
      subjects with (FAM+) and 45 subjects without (FAM-) a family history of
      hypertension. Arterial blood pressure, left ventricular geometry and function,
      and plasma EO levels were measured in each subject. RESULTS: Plasma EO levels
      were higher in the FAM+ subjects (221.5 +/- 10.95 versus 179.6 +/- 9.58 pmol/l, P
      = 0.004), and directly correlated with both systolic (r = 0.417, P < 0.0001) and
      diastolic blood pressure (r = 0.333, P = 0.002). Plasma EO was inversely related
      to an index of cardiac diastolic function determined as the ratio between the
      early and late peak flow velocity (r = -0.286, P = 0.012) and isovolumetric
      relaxation time (IVRT) (r = 0.32, P = 0.003). The IVRT was also significantly
      higher in FAM+, correlated with the IVRT (r = 0.32, P = 0.003). The IVRT was also
      significantly higher in FAM+, whereas the other echocardiographic parameters were
      similar to FAM-. CONCLUSIONS: Among the offspring of families with a positive
      history of hypertension, circulating EO levels and blood pressure are increased.
      Plasma EO levels are related to alterations of some indexes of diastolic heart
      function in these individuals.

PMID- 16093913
TI  - Differential expression of nNOS mRNA and protein in the nucleus tractus solitarii
      of young and aged Wistar-Kyoto and spontaneously hypertensive rats.
AB  - OBJECTIVE: To examine neuronal nitric oxide synthase (nNOS) mRNA and protein in
      the nucleus tractus solitarii (NTS) and paraventricular hypothalamic nucleus
      (PVN) of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) during
      their life span. METHODS: By means of in situ hybridization and
      immunohistochemistry, we evaluated nNOS mRNA and protein in the NTS and PVN of 15
      day- and 1-, 2-, 4-, 8- and 12-month-old SHR and WKY rats. RESULTS: Two patterns
      of nNOS expression were observed in two subnuclei of the NTS: medial (NTSm) and
      central (NTSce). NTSce of the SHR exhibited higher nNOS mRNA and protein
      expression in all ages analyzed when compared to the age-matched WKY. Increased
      amounts of nNOS mRNA and protein were seen in the NTSm only during the early life
      of SHR (15 days to 4 months) when compared to WKY, suggesting a special role of
      this circuitry before the establishment of hypertension. No changes were seen in
      nNOS mRNA and protein expression in the PVN of the SHR in comparison to the WKY
      in all periods. nNOS analysis during the life span showed either a decrease or no
      change in nNOS mRNA expression in NTS or PVN associated with increased nNOS
      protein at some analyzed periods, suggesting the differential regulation of nNOS
      mRNA and protein during aging. CONCLUSIONS: Data suggest that different NTS
      subnuclei exhibit nNOS changes in different phases of the life of SHR and this
      might be important during the development of hypertension in these animals.

PMID- 16093914
TI  - Angiotensin II modulates renal sympathetic neurotransmission through nitric oxide
      in AT2 receptor knockout mice.
AB  - OBJECTIVE: Angiotensin (Ang) II enhances renal sympathetic neurotransmission and
      stimulates nitric oxide (NO) release. The present study investigates whether Ang
      II-mediated modulation of sympathetic neurotransmission is dependent on NO
      production in the kidney. AT2 -/y receptor-deficient mice are used to identify
      the Ang II receptor subtype involved. METHODS: Mice kidneys were isolated and
      perfused with Krebs-Henseleit solution. Drugs were added to the perfusion
      solution in a cumulative manner. Release of endogenous noradrenaline (NA) was
      measured by high-performance liquid chromatography (HPLC). AT1 receptor
      expression was analysed by real-time polymerase chain reaction (PCR). RESULTS:
      Ang II (0.01-30 nmol/l) dose dependently increased pressor responses in kidneys
      of AT2 -/y mice and wild-type (AT2 +/y) mice. Maximal pressor responses and EC50
      values for Ang II was greater in AT2 -/y than in AT2 +/y mice. L-NAME (N(omega)
      nitro-L-arginine methyl ester; 0.3 mmol/l) enhanced Ang II-induced pressor
      responses in both strains. In AT2 -/y mice, Ang II-induced facilitation of NA
      release was more pronounced than in AT2 +/y mice. L-NAME reduced Ang II-mediated
      facilitation of NA release in both strains. This reduction was more potent in AT2
      -/y mice. In kidneys of AT2 -/y mice the AT1 receptor expression was
      significantly upregulated. CONCLUSION: These results suggest that activation of
      AT1 receptors by Ang II releases NO in mouse kidney to modulate sympathetic
      neurotransmission. Since AT1 receptors are upregulated in AT2 -/y mice kidneys,
      NO-dependent effects were greater in these mice. Thus, NO seems to play an
      important modulatory role for renal sympathetic neurotransmission.

PMID- 16093915
TI  - Estrogen reduces endothelial progenitor cell senescence through augmentation of
      telomerase activity.
AB  - BACKGROUND: Recent studies have demonstrated that aging or senescence constitutes
      a potential limitation to the ability of endothelial progenitor cells (EPCs) to
      sustain ischemic tissue and repair. Conversely, estrogens have been shown to
      accelerate recovery of the endothelium after vascular injury. OBJECTIVE: To
      investigate whether estrogens are able to prevent senescence of EPCs. METHODS AND
      RESULTS: Human EPCs were isolated from peripheral blood and characterized. After
      ex-vivo cultivation, the cells became senescent as determined by acidic beta
      galactosidase staining. 17beta-estradiol dose-dependently inhibited the onset of
      EPC senescence in culture. Because cellular senescence is critically influenced
      by telomerase, which elongates telomeres, we measured telomerase activity using a
      polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay (ELISA)
      technique. 17beta-estradiol significantly increased telomerase activity.
      Interestingly, reverse transcriptase-PCR analysis demonstrated that 17beta
      estradiol dose-dependently increased the catalytic subunit, telomerase reverse
      transcriptase (TERT) - an effect that was significantly inhibited by
      pharmacological phosphatidylinositol 3-kinase (PI3-K) blockers (either wortmannin
      or LY294002). Because the expression of TERT is regulated by the PI3-K/Akt
      pathway, we examined the effect of 17beta-estradiol on Akt activity in EPCs.
      Immunoblotting analysis revealed that 17beta-estradiol dose-dependently led to
      phosphorylation and, thus, to activation of Akt in EPCs. We also examined whether
      the protective effect of 17beta-estradiol on EPC senescence translates into the
      augmentation of mitogenic activity in EPCs. A [3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenol)-2-(4-sulfophenyl)-2H-tetrazolium] (MTS) assay demonstrated
      that the mitogenic potential in EPCs treated with 17beta-estradiol exceeded that
      in untreated (control) EPCs (P < 0.01). In addition, EPCs released vascular
      endothelial growth factor (VEGF) protein--an effect that was significantly
      augmented by 17beta-estradiol. Finally, in a Matrigel assay, EPCs treated with
      both 17beta-estradiol and VEGF were shown to be more likely to integrate into the
      network formation than those treated with VEGF alone. CONCLUSION: The inhibition
      of EPC senescence by estrogen in vitro may improve the functional activity of
      EPCs in a way that is important for potential cell therapy.

PMID- 16093916
TI  - Normative values for intima-media thickness and distensibility of large arteries
      in healthy adolescents.
AB  - OBJECTIVE: Sonographic evaluation of arterial wall morphology and elasticity is
      increasingly accepted as a non-invasive tool in cardiovascular assessment.
      Several studies suggest that intima-media thickness (IMT) and arterial elasticity
      indices may sensitively reflect different vasculopathic processes in children.
      However, normative values and the impact of adolescent growth are largely
      unknown. METHODS: We assessed the IMT of the common carotid (cIMT) and femoral
      arteries (fIMT), carotid elasticity indices and interacting anthropometric
      factors in 247 healthy subjects aged 10-20 years. RESULTS: cIMT, fIMT,
      incremental elastic modulus (Einc) and circumferential wall stress (CWS) were
      positively, and distensibility coefficient (DC) inversely, correlated with age,
      height, body mass index (BMI), systolic blood pressure (BP) and brachial pulse
      pressure (r = 0.56 to -0.45, P < 0.05 to 0.0001). DC (r = -0.29, P < 0.0001) and
      stiffness index beta (r = 0.25, P < 0.0001), but not Einc, were significantly
      associated with cIMT independently of age. All vascular parameters showed non
      Gaussian distributions. Excessively high IMT was associated with BMI and pulse
      pressure above the 90th percentile, and elevated Einc with high-normal BMI.
      Multivariate analysis identified independent positive effects of standardized BMI
      and brachial pulse pressure on normalized cIMT, negative effects of systolic BP
      and cIMT on DC, a positive effect of cIMT on stiffness, and positive effects of
      systolic BP and BMI on Einc and CWS. CONCLUSIONS: Morphological and functional
      measures of large arteries should be normalized to take account of changes during
      adolescence and skewed distributions. Relative body mass, systolic blood pressure
      and/or pulse pressure are determinants of IMT and elasticity.

PMID- 16093917
TI  - Alterations in vascular matrix metalloproteinase due to ageing and chronic
      hypertension: effects of endothelin receptor blockade.
AB  - OBJECTIVE: To determine the effects of age and dual endothelin (ET)A/ETB receptor
      antagonism (bosentan) on aortic matrix metalloproteinase (MMP) abundance and
      tissue inhibitor of metalloproteinase (TIMP) expression in normotensive Wistar
      Kyoto (WKY) and spontaneously hypertensive rats (SHR). METHODS: Male SHR and
      control WKY rats were randomly assigned to receive placebo or bosentan (100 mg/kg
      per day) for 3 months. Animals were killed under terminal anaesthesia at either
      20 weeks (adult) or 17-20 months (senescent). Aortic gelatinase activity was
      determined by zymography, whereas MT-1 MMP and TIMP-1 expression were assessed by
      immunoblotting. RESULTS: In WKY rats, aortic MMP-2 but not proMMP-2 activity was
      3.6-fold higher (P < 0.02) in the senescent compared with the adult group. TIMP-1
      (twofold) and MT-1 MMP (3.8-fold) expression increased (P < 0.05) with age in the
      WKY groups. Short-term hypertension (adult SHR versus adult WKY) increased MMP-2
      to 74.7 +/- 14.1 from 18.9 +/- 3.5 arbitrary units (AU) (P = 0.0012), but did not
      alter proMMP-2 activity. This increased further on progression to chronic
      hypertension (117.4 +/- 12.2 versus 74.7 +/- 14.1 AU; P < 0.02). Bosentan
      decreased MMP-2 (78.9 +/- 3.8 versus 117.4 +/- 12.2 AU; P = 0.014) and proMMP-2
      activity (P < 0.006) in the senescent SHR group. CONCLUSION: Ageing and the
      development/progression of hypertension are associated with increased MMP-2
      activity in the aorta, which is consistent with ongoing remodelling of the
      vasculature. However, the underlying mechanisms regulating MMP-2 abundance in
      ageing and hypertension appear to be divergent, as MT-1 MMP expression is
      differentially altered. Dual ETA/ETB receptor antagonism did not alter the age
      dependent increase in aortic MMP activity in normotensive rats. However, bosentan
      decreased pro and active MMP-2 activity in senescent SHR rats, indicating that ET
      modulates late events in vascular remodelling in hypertension.

PMID- 16093918
TI  - Decreased plasma levels of soluble receptor for advanced glycation end-products
      in patients with essential hypertension.
AB  - OBJECTIVES: Advanced glycation end-products (AGE) may cause vascular stiffening
      by forming crosslinks through the collagen molecule or by interaction with their
      cellular transductional receptor (RAGE). A secreted isoform of RAGE, termed
      soluble RAGE (sRAGE), may contribute to the removal/detoxification of AGE by
      acting as a decoy. Here we studied the plasma sRAGE levels in hypertensive and
      normotensive human subjects. We also investigated the relationship between blood
      pressure parameters and plasma sRAGE concentrations. DESIGN: A cross-sectional
      case-control study. SETTING AND PARTICIPANTS: The outpatient clinic of a
      university teaching hospital. Participants were 147 never-treated patients with
      essential hypertension (87 men and 60 women, aged 50 +/- 10 years) and 177
      normotensive controls (118 men and 59 women, aged 49 +/- 10 years). MAIN OUTCOME
      MEASURES: Plasma sRAGE levels determined by enzyme-linked immunosorbent assay,
      systolic blood pressure (SBP), diastolic blood pressure, pulse pressure (PP) and
      mean arterial pressure. RESULTS: The plasma concentration of sRAGE [median
      (interquartile range)] was 1206 (879-1658) pg/ml in hypertensive subjects and
      1359 (999-2198) pg/ml in normotensive controls (P = 0.002). Simple correlation
      analysis revealed that log-transformed sRAGE levels were inversely correlated
      with SBP (r = -0.11; P < 0.001) and PP (r = -0.23; P < 0.001). Forward-selection
      multiple regression analysis revealed that log-transformed sRAGE levels were
      determined more strongly by PP (F = 3.127, P < 0.001). CONCLUSIONS: Plasma sRAGE
      levels are decreased in patients with essential hypertension and are inversely
      related to PP. Our results raise the possibility that sRAGE may play a role in
      arterial stiffening and its complications.

PMID- 16093919
TI  - Mechanisms of adenosine-induced renal vasodilatation in hypertensive patients.
AB  - BACKGROUND: Adenosine is an endogenous nucleoside with potent vasodilatory
      capacities, released under ischaemic conditions in particular. Its mechanisms of
      action, however, remain elusive. OBJECTIVE: To evaluate the role of adenosine,
      using a non-selective purinergic receptor antagonist, and the possible
      involvement of nitric oxide in this mechanism. In addition, the production of
      renin and catecholamines was studied during infusion of adenosine, caffeine, or
      both. METHODS: Thirty-three hypertensive patients who underwent diagnostic renal
      angiography received intrarenal infusions of adenosine either alone or in
      combination with caffeine or the nitric oxide synthase inhibitor, N-monomethyl-L
      arginine (L-NMMA). The effects on renal blood flow (RBF) were assessed by the
      xenon-133 washout technique and both arterial and renal venous blood samples were
      taken for measurement of renin and catecholamine concentrations. Intra-arterial
      blood pressure and heart rate were monitored continuously. RESULTS: Adenosine
      induced a dose-dependent vasodilatation. Caffeine alone did not change RBF, but
      shifted the dose-response curve of adenosine to the right during concomitant
      infusion of caffeine. RBF during combined infusion of L-NMMA and adenosine was
      not different from that during adenosine alone, but the decrease in renal
      vascular resistance was less pronounced during this combination. Renin secretion
      did not change during the infusion of either adenosine alone or adenosine in
      combination with caffeine. Catecholamine concentrations also did not change
      during any of the experiments. CONCLUSIONS: Adenosine induces vasodilatation in
      the human hypertensive kidney and this effect is mediated by the adenosine
      receptor. Nitric oxide plays, at most, a minor part in the adenosine-induced
      vasodilatation. Furthermore, renin secretion is not affected by adenosine and
      caffeine.

PMID- 16093920
TI  - Vascular but not cardiac remodeling is associated with superoxide production in
      angiotensin II hypertension.
AB  - OBJECTIVE: Angiotensin (Ang) II increases reactive oxygen species (ROS),
      decreases nitric oxide (NO) bioavailability and promotes cardiovascular
      remodeling. ROS have been identified as critical second messengers of the trophic
      responses by Ang II. In rats with Ang II-induced hypertension, we investigated
      the role of ROS in cardiac hypertrophy as well as the remodeling of aortas and
      mesenteric (resistance) arteries. METHODS: Sprague-Dawley rats received Ang II
      (0.7 mg/kg per day by mini-pump, n = 7) or vehicle (n = 7) for 5 days.
      Endothelium-dependent relaxation to acetylcholine (EDR) in aortas was determined
      in organ baths and in mesenteric resistance vessels in a pressurized myograph.
      Superoxide (O2) production was measured by lucigenin chemiluminescence, laser
      confocal fluorescence microscopy (LCM) and NADPH oxidase assay. RESULTS: Ang II
      treated rats developed hypertension (183 +/- 3 versus 138 +/- 4 mmHg, P < 0.05),
      increased aortic O2 (50%), aortic hypertrophy (12%) and impaired EDR. Mesenteric
      arteries manifested impaired EDR, increased NADPH oxidase activity (356%) and
      eutrophic inward remodeling (decreased lumen diameter and increased wall/lumen
      ratio). However, although Ang II-treated rats developed cardiac hypertrophy
      (13%), this was not accompanied by an increase in cardiac O2, as measured by
      lucigenin, LCM or NADPH oxidase assay. On the other hand, cardiac calcineurin, a
      molecule that promotes cardiac hypertrophy linked to Ang II, was increased by 40%
      (52 +/- 8 versus 33 +/- 5 pmol/min per mg protein, P < 0.05). CONCLUSION: These
      studies demonstrate that the role of ROS in Ang II-induced vascular remodeling
      differ across vascular territories. Although in conduit and resistance vessels,
      vascular hypertrophy and endothelial dysfunction are linked to increased ROS
      production, cardiac hypertrophy is not. Instead, cardiac hypertrophy is
      associated, at least in part, with an increase in calcineurin. These studies
      unveil novel mechanisms that may play an important role in the pathogenesis of
      cardiac and vascular injury in hypertension.

PMID- 16093921
TI  - Left ventricular diastolic dysfunction is accompanied by increased aortic
      stiffness in the early stages of essential hypertension: a TDI approach.
AB  - OBJECTIVE: To investigate the inter-relationship between aortic stiffness and
      left ventricular (LV) diastolic function in subjects with newly diagnosed
      uncomplicated essential hypertension. METHODS: We studied 106 consecutive newly
      diagnosed subjects (aged 51 years, 80 males) with stage I-II essential
      hypertension, and 50 normotensives matched for age, sex and body mass index. LV
      diastolic function was estimated by pulsed tissue Doppler imaging (TDI)
      echocardiography, averaging diastolic mitral annular velocity measurements (Emav,
      Amav, Emav/Amav ratio) from four separate sites (basal septal, lateral, anterior,
      and inferior LV wall). Moreover, aortic stiffness was evaluated by non-invasive
      carotid-femoral pulse wave velocity (c-f PWV) measurement. RESULTS: Hypertensives
      compared with normotensives exhibited greater LV mass index and Amav (110 versus
      95 g/m and 10 versus 8.8 cm/s, respectively, P < 0.001 for both cases), and
      greater c-f PWV (8.47 versus 7.48 m/s, P < 0.03), as well as lower Emav and
      Emav/Amav values, (8.4 versus 10 cm/s and 0.82 versus 1.15, respectively, P <
      0.001 for both cases). In the group of hypertensives, a univariate analysis
      revealed that c-f PWV was negatively associated with Emav (r = -0.305, P =
      0.005), as well as with Emav/Amav ratio (r = -0.437, P < 0.001). Moreover, a
      multivariate analysis showed that the TDI-derived Emav/Amav ratio was
      significantly associated with age (P = 0.001), relative wall thickness (P =
      0.006) and c-f PWV (P = 0.03), while the conventional Doppler-derived E/A ratio
      was significantly associated only with age (P = 0.001). CONCLUSIONS: TDI-detected
      LV diastolic dysfunction is accompanied by increased aortic stiffness in newly
      diagnosed essential hypertension, suggesting that there may be a common
      pathophysiological pathway linking these two entities.

PMID- 16093922
TI  - Increased myocardial repolarization lability and reduced cardiac baroreflex
      sensitivity in individuals with high-normal blood pressure.
AB  - BACKGROUND: Recent guidelines for the management of arterial hypertension have
      proposed that, to prevent cardiovascular disease, lifestyle modifications are
      required even in the case of high-normal blood pressure (HNBP). OBJECTIVE: To
      assess myocardial repolarization and spontaneous cardiac baroreflex sensitivity
      (BRS) in newly diagnosed and never-treated individuals. DESIGN AND PARTICIPANTS:
      We studied healthy individuals with HNBP according to the 2003 European Society
      of Hypertension-ESC guidelines and, for comparison, patients with renovascular
      hypertension (RVH) and healthy individuals with normal blood pressure (NBP). MAIN
      OUTCOME MEASURES: Electrocardiogram and beat-to-beat blood pressure were recorded
      and spontaneous cardiac baroreflex sensitivity and the temporal QT interval
      variability index (QTVI) were calculated. RESULTS: Individuals with HNBP had
      increased QTVI values compared with those with NBP (-1.23 +/- 0.37 compared with 
      1.52 +/- 0.26; P < 0.05), whereas patients with RVH had additionally increased
      QTVI values that were greater than those in healthy individuals with NBP or HNBP
      (-0.81 +/- 0.75; P < 0.05 compared with both groups). BRS was reduced in both
      groups of individuals with increased blood pressures compared with NBP (8.2 +/-
      4.1 ms/mmHg for individuals with HNBP, 6.1 +/- 4.3 ms/mmHg for patients with RVH
      and 10.8 +/- 3.5 ms/mmHg for NBP; P < 0.05 for both). CONCLUSION: In otherwise
      healthy individuals, even a moderate blood pressure increase is associated with
      increased myocardial repolarization lability and reduced baroreflex sensitivity
      (BRS). Patients with RVH have an additionally increased QTVI, with values similar
      to those reported in congestive heart failure. Future studies are needed to
      establish the value of QTVI and BRS measurements among individuals with HNBP in
      predicting the risk of progression to hypertension and end-organ damage.

PMID- 16093923
TI  - Vascular and renal effects of vasopeptidase inhibition and angiotensin-converting
      enzyme blockade in spontaneously diabetic Goto-Kakizaki rats.
AB  - BACKGROUND: The renin-angiotensin system plays an important role in the
      pathogenesis of diabetes-induced vascular and renal complications. Vasopeptidase
      inhibitors simultaneously inhibit angiotensin-converting enzyme (ACE) and neutral
      endopeptidase. OBJECTIVE: To compare the effectiveness of vasopeptidase
      inhibition and ACE inhibition in preventing hypertension, endothelial dysfunction
      and diabetic nephropathy in spontaneously diabetic Goto-Kakizaki (GK) rats.
      METHODS: Eight-week-old GK rats received omapatrilat (40 mg/kg) or enalapril (30
      mg/kg) for 12 weeks, either during a normal-sodium or high-sodium diet (7% w/w).
      Blood pressure, arterial functions and renal morphology were determined. RESULTS:
      Blood pressure and albuminuria were increased in GK rats compared to non-diabetic
      Wistar controls. Endothelium-dependent vascular relaxation in response to
      acetylcholine (ACh) and endothelium-independent vascular relaxation in response
      to sodium nitroprusside (SNP) were impaired in GK rats. Experiments with N-nitro
      L-arginine methyl ester (L-NAME), diclofenac, and L-NAME + diclofenac suggested
      that cyclooxygenase and endothelium-derived hyperpolarizing factor components of
      endothelium-dependent vascular relaxation were also impaired. A high-sodium diet
      aggravated hypertension and diabetes-induced vascular and renal complications.
      Omapatrilat and enalapril normalized blood pressure and albuminuria during the
      normal-sodium diet, and effectively ameliorated diabetes-induced renal
      complications also during the high-sodium diet. However, omapatrilat improved
      endothelium-dependent relaxation to ACh to a greater extent (85 +/- 5%) than
      enalapril (68 +/- 6%, P < 0.05). Diclofenac pre-incubation eliminated this
      difference between omapatrilat and enalapril in ACh-induced vascular relaxation,
      suggesting that it was mediated, at least in part, via the cyclooxygenase
      pathway. CONCLUSIONS: Despite comparable blood pressure-lowering and
      renoprotective properties, omapatrilat may be more effective in preventing
      vascular dysfunction during diabetes compared to enalapril in GK rats.

PMID- 16093925
TI  - Estimating the return-on-investment from changes in employee health risks on the
      Dow Chemical Company's health care costs.
AB  - OBJECTIVE: We sought to estimate the impact of corporate health-management and
      risk-reduction programs for The Dow Chemical Company by using a prospective
      return-on-investment (ROI) model. METHODS: The risk and expenditure estimates
      were derived from multiple regression analyses showing relationships between
      worker demographics, health risks, and medical expenditures. RESULTS: A "break
      even" scenario would require Dow to reduce each of 10 population health risks by
      0.17% points per year over the course of 10 years. More successful efforts at
      reducing health risks in the population would produce a more significant ROI for
      the company. CONCLUSIONS: Findings from this study were incorporated into other
      components of a business case for health and productivity management, and these
      supported continued investments in health improvement programs designed to
      achieve risk reduction and cost savings.

PMID- 16093926
TI  - The association of health risks with on-the-job productivity.
AB  - OBJECTIVE: Decreased on-the-job productivity represents a large yet poorly
      characterized indirect cost to employers. We studied the impact of employee
      health risk factors on self-reported worker productivity (presenteeism). METHODS:
      Using a brief version of the Work Limitation Questionnaire incorporated into a
      Health Risk Appraisal, 28,375 employees of a national company responded to the
      survey. The association between health risks and work limitation and each of the
      four domains was examined. Percentage of lost productivity also was estimated.
      RESULTS: Ten of 12 health risk factors studied were significantly associated with
      self-reported work limitations. The strength of the associations varied between
      risks and the four domains of work limitation. Perception-related risk factors
      such as life dissatisfaction, job dissatisfaction, poor health, and stress showed
      the greatest association with presenteeism. As the number of self-reported health
      risk factors increased, so did the percentage of employees reporting work
      limitations. Each additional risk factor was associated with 2.4% excess
      productivity reduction. Medium and high-risk individuals were 6.2% and 12.2% less
      productive than low-risk individuals, respectively. The annual cost of lost
      productivity in this corporation was estimated at between 99Mdollars and
      185Mdollars or between 1392dollars and 2592dollars per employee. CONCLUSIONS:
      Health risk factors represent additional causes of lost productivity.

PMID- 16093927
TI  - Association between arsenic exposure and a measure of subclinical sensory
      neuropathy in Bangladesh.
AB  - OBJECTIVES: We examined the association between arsenic exposure and peripheral
      neuropathy in Bangladesh, where the population has been chronically exposed to
      arsenic in drinking water. METHODS: We conducted a cross-sectional study of 137
      subjects derived from a larger cohort. Exposure measures included individual
      water arsenic concentration, cumulative arsenic index, and urinary arsenic
      concentration taken at two time points (2001 and 2003). The primary outcome
      measurement was elevated vibrotactile threshold, as measured by a vibration
      sensitivity tester (Vibratron II). RESULTS: Arsenic exposure was associated with
      elevated toe vibration threshold (TVT). Specifically, cumulative arsenic index
      and urinary arsenic (2001) were both significantly associated with elevated TVT
      (P = 0.02 and P = 0.009, respectively) after adjustment for age and gender.
      CONCLUSIONS: Increased arsenic exposure, as measured by both cumulative and
      urinary measures, was associated with evidence of subclinical sensory neuropathy.

PMID- 16093928
TI  - Occupation and upper aerodigestive tract cancers: a follow-up study in Sweden.
AB  - OBJECTIVES: We sought to examine the associations between occupation and upper
      aerodigestive tract cancers at various anatomic sites. METHODS: The Swedish
      Family-Cancer Database was used to calculate standardized incidence ratios for
      different occupational groups, adjusted for age, period, and socioeconomic
      status. RESULTS: Male dentists showed an increased risk for tongue cancer;
      hairdressers had an increased risk for tongue and larynx cancers among men and
      pharynx cancer among women; launderers and dry cleaners showed an increased risk
      for pharynx cancer among men and lip cancer among women; outdoor occupations such
      as fishermen, seamen, transport, and construction workers showed increased risks
      for lip cancer. CONCLUSIONS: Although smoking and alcohol drinking can explain
      some of these results, increased risks found for dentists, hairdressers, and
      launderers and dry cleaners may partly be explained by their work-related
      exposures; increased risks of lip cancer in outdoor occupations can be explained
      by sunlight exposure.

PMID- 16093929
TI  - Overlooked diagnoses in chronic pain: analysis of survivors of electric shock and
      lightning strike.
AB  - OBJECTIVE: Patients who survive lightning strikes are rarely seen in clinical
      practice and patients with electrical injury are seen infrequently. This article
      reports the most commonly overlooked diagnoses so that physicians can improve
      their evaluations. METHODS: A total of 19 patients who survived a lightning
      strike and 53 patients who survived electrical shock had a partial or complete
      multidisciplinary evaluation at Mensana Clinic. A variety of diagnostic studies
      were ordered. RESULTS: In 19 lightning strike survivors, referring physicians did
      not mention 133 diagnoses, later established by Mensana Clinic. The overlooked
      diagnosis rate was 93%. In 53 patients who survived electrical shock, referring
      physicians did not mention 436 diagnoses, later established by Mensana Clinic.
      The overlooked diagnosis rate was 98.2%. CONCLUSIONS: Patients who survive
      electric shock and lightning strikes are often misdiagnosed because they are
      infrequently seen in a medical practice.

PMID- 16093930
TI  - Insect repellents, phenoxyherbicide exposure, and non-Hodgkin's lymphoma.
AB  - OBJECTIVE: We sought to test a hypothetical explanation of contradictory results
      in studies of phenoxyherbicides and NHL, that the exposure of rubber gloves
      recommended for use by farmers when mixing or applying pesticides simultaneously
      to 2,4-D (2,4-dichlorophenoxyacetic acid), DEET (N,N-diethyl-m-toluamide), and
      ultraviolet rays increased their permeability to 2,4-D. METHODS: We conducted a
      case (NHL n = 513)/control (n = 1506) study among men using age; province of
      residence; exposure to insect repellents containing DEET, phenoxy-herbicides, or
      dicamba; and gloves when handling pesticides. RESULTS: Using conditional logistic
      regression, the stratum with reported exposure to mecoprop, to DEET and the use
      of rubber gloves had higher odds ratios (3.86; 95% confidence interval = 1.57
      9.49) compared with strata with other combinations. CONCLUSIONS: In conclusion,
      the etiologic complexity of NHL was demonstrated.

PMID- 16093931
TI  - Risk assessment for asbestos-related cancer from the 9/11 attack on the World
      Trade Center.
AB  - OBJECTIVE: We sought to estimate the lifetime risk of asbestos-related cancer for
      residents of Lower Manhattan attributable to asbestos released into the air by
      the 9/11 attack on New York City's World Trade Center (WTC). METHODS: Exposure
      was estimated from available data and reasoned projections based on these data.
      Cancer risk was assessed using an asbestos risk model that differentiates
      asbestos fiber-types and the US Environmental Protection Agency's model that does
      not differentiate fiber-types and combines mesothelioma and lung cancer risks.
      RESULTS: The upper limit for the expected number of asbestos-related cancers is
      less than one case over the lifetime of the population for the risk model that is
      specific for fiber-types and 12 asbestos-related cancers with the US
      Environmental Protection Agency's model. CONCLUSIONS: The cancer risk associated
      with asbestos exposures for residents of Lower Manhattan resulting from the
      collapse of the WTC is negligible.

PMID- 16093932
TI  - Association between congenital anomalies and paternal exposure to agricultural
      pesticides depending on mother's employment status.
AB  - OBJECTIVE: We analyzed the association between fetal death from congenital
      anomalies and paternal agricultural occupation in mothers who were employed and
      in housewives. MATERIALS AND METHODS: The data consist of individual records from
      the Spanish Birth Register (1995-1999). RESULTS: The adjusted relative risk of
      fetal death in agricultural workers compared with nonagricultural was 1.24 (95%
      confidence interval = 0.38- 4.02) in mothers who were employed and 1.68 (95%
      confidence interval = 1.03-2.73) in housewives. CONCLUSION: The risk of fetal
      death in the offspring of agricultural workers exposed to pesticides around the
      time of conception was higher than in the offspring of nonagricultural workers in
      mothers who were housewives but not in mothers who worked outside the home.

PMID- 16093933
TI  - The impact of social and organizational factors on workers' use of personal
      protective equipment: a multilevel approach.
AB  - OBJECTIVE: On the basis of the job demands-control-support model by Karasek and
      Theorell, we investigated how social and organizational factors influence
      workers' use of personal protective equipment (PPE). METHODS: A cross-sectional
      study was performed among 1420 workers in 203 motor vehicle-repair garages.
      Multilevel modeling was performed to account for the hierarchical structure of
      the data. RESULTS: Social and management support correlated positively with PPE
      use at the worker level. Low demands measured at the garage level and having a
      health and safety management system at the garage also correlated with active use
      of PPE. An interaction effect between social support and garage-level demands was
      observed. CONCLUSIONS: In addition to health information and provision of PPE,
      focusing on social and organizational factors seems necessary to get more workers
      to comply with the instructions on PPE use.

PMID- 16093934
TI  - Illness absence patterns among employees in a petrochemical facility: impact of
      selected health risk factors.
AB  - BACKGROUND: Illness absence in a working population is a complex phenomenon and
      can be influenced by many factors, such as age, gender, and personal health risk
      factors. The current study used prospectively collected employee health risk and
      morbidity data to examine illness absence patterns for a working population and
      to quantify the impact of selected health risk factors on employee illness
      absence. METHODS: The study population consisted of 2550 regular employees
      working at a Texas petrochemical facility. Morbidity data were extracted from the
      company's Health Surveillance System, and records of absences were derived from
      personnel and payroll systems. The morbidity frequency rate and average duration
      of absence per employee per year were calculated by age, gender, and selected
      health risk factors, including smoking, body mass index, cholesterol,
      triglycerides, hypertension, and fasting glucose. RESULTS: Morbidity frequency
      rates and average duration of absence increased with age and with the presence of
      health risk factors. The absence frequency rate increased with an increase in the
      number of risk factors present from no risk factors (11.8 per 100 employees) to
      four or more risk factors (32.3 per 100 employees). The number of workdays lost
      also increased with the number of risk factors present, with the least number of
      workdays lost by employees with zero risk factors (4.1 day), followed by one (6.4
      days), two (8.8 days), three (9.3 days), and four or more risk factors (12.6
      days). CONCLUSIONS: The impact of employee health risk factors has been shown in
      this study to be associated with absence frequency and duration of absence.
      Reduction in employee health risk factors can be an effective means of improving
      employees' health and increasing a company's productivity.

PMID- 16093935
TI  - Is forced oscillation technique useful in the diagnosis of occupational asthma?
AB  - OBJECTIVE: The aim of the study was to determine whether the forced oscillation
      technique (FOT), which does not require active cooperation, may be useful to
      assess bronchial responsiveness in patients with suspected occupational asthma
      (OA). METHODS: Changes in resistances evaluated by FOT, and DeltaFEV1 measured
      during methacholine challenge test were compared in 77 adults referred for
      suspected OA. Spearman correlations and ROC curves were used. RESULTS: R0 at the
      final dose of methacholine (R0hmd) and DeltaR0 were strongly correlated with
      DeltaFEV1 (p < 0.001). The ROC curves showed that R0hmd >or= 240% predicted was
      the best cut-off value to discriminate subjects with OA from nonasthmatic
      subjects (sensitivity: 80%, specificity: 76%). CONCLUSION: FOT can be proposed as
      an alternative method for the assessment of bronchial responsiveness in subjects
      with suspected OA, unable to correctly perform forced expiratory maneuvers.

PMID- 16093936
TI  - Identification of occupational cancer risks in British Columbia: a population
      based case-control study of 1129 cases of bladder cancer.
AB  - OBJECTIVE: We collected information on lifetime occupational histories, smoking,
      and alcohol consumption from 15,463 incident cancer cases. Occupational risk
      factors for bladder cancer are presented in this report. METHOD: A matched case
      control design was used. All cases were diagnosed with bladder cancers, with
      controls being internal controls consisting of all other cancer sites, excluding
      lung and unknown primary. Data were analyzed using conditional logistic
      regression for matched sets data and the likelihood ratio test. RESULTS: Excess
      bladder cancer risks was observed in a number of occupation and industries,
      particularly those involving exposure to metals, including aluminum, paint and
      solvents, polycyclic aromatic hydrocarbons, diesel engine emissions, and
      textiles. CONCLUSIONS: The results of our study are in line with those from the
      literature and further suggest that exposure to silica and to electromagnetic
      fields may carry an increased risk of bladder cancer.

PMID- 16093937
TI  - Working words: real-life lexicon of North American workers.
AB  - OBJECTIVE: This study describes a new computer methodology for analyzing workers'
      free text work descriptions. METHODS: Computerized lexical analysis was applied
      to work descriptions of participants in the Lung Health Study, a smoking
      cessation study in persons with early chronic obstructive pulmonary disease. Text
      was parsed and analyzed as single term roots and pairs of roots commonly
      occurring together. RESULTS: The frequencies of terms reflect the work of a
      population; our subjects' most frequently used terms included "sale, office,
      service, business, engine[er], secretary, construct, driv[e], comput[e], teach,
      truck." Standard classification schemes (NAICS and SOC) and textbooks use terms
      inconsistent with those of actual workers. Many common empirical terms imply both
      industry and job information content, although traditional coding schemes
      separate industry and job title. CONCLUSIONS: Formal analyses of language may
      facilitate communication, identify translation priorities, and allow automated
      work coding.

PMID- 16093940
TI  - The choice of intramedullary devices for the femur and the tibia in osteogenesis
      imperfecta.
AB  - The results of intramedullary rodding of 50 femoral and 25 tibial segments were
      analyzed retrospectively. The techniques of femoral rodding included single Rush
      rodding, dual Rush rodding and Sheffield telescoping rodding. Single Rush rods or
      Sheffield rods were used in the tibia. The frequencies of fractures following
      rodding and implant-related complications and the interval between initial
      rodding and rod revision were analyzed. The longevity of the rods was evaluated
      by survival analysis. In the femur, dual Rush rods and Sheffield rods were
      equally effective and both were superior to a single Rush rod with reference to
      each of the outcome variables. The technique of dual Rush rodding was more
      demanding than telescoping rodding. In the tibia, a single Rush rod was as
      effective as a Sheffield telescoping rod. Based on our results, a single Rush rod
      would be the preferred implant in the tibia while in the femur, dual Rush rods or
      a Sheffield telescoping rod may be preferred.

PMID- 16093941
TI  - Growth and progression of adolescent idiopathic scoliosis in girls.
AB  - The progression velocity of scoliosis was studied for 535 consecutive girls with
      untreated adolescent idiopathic scoliosis. At the first visit the mean age of the
      patients was 13.9 years (range 9-19 years), the mean magnitude of the major
      curves was 23.4 degrees (range 5-60 degrees), and that of the minor curves 16.4
      degrees (range 0-49 degrees). The median follow-up time was 1.1 years (mean 1.4,
      range 0.5-6.3 years). The right thoracic curves were most progressive. In the
      major left thoracic and left lumbar curve types, initial minor curves progressed
      faster than major curves. The scoliosis progressed faster in patients with minor
      thoracic kyphosis. In these patients major right thoracic curves were more
      common. The progression of scoliosis was clearly dependent on the growth
      velocity, also, the greater the curve at the first visit, the greater was the
      progression. The progression was most notable with a growth velocity of >or=2
      cm/year, at ages between 9 and 13 years, bone ages between 9 and 14 years, Risser
      signs 0-1, and between 0.5-2 years before menarche.

PMID- 16093942
TI  - The natural history of developmental dysplasia of the hip: sonographic findings
      in infants of 1-3 months of age.
AB  - The natural history of sonographic developmental dysplasia of the hip was
      determined in a population-based study in which 5170 infants were screened by
      ultrasound using Graf's method. Of the normal hips at the age of 1 month, 99.6%
      were still normal at the age of 3 months. Of the immature type IIa/IIa+ and type
      IIa- hips, if untreated, 95.3 and 84.4% had become normal, respectively. Of the
      infants with type IIc, D and III/IV hips at the age of 1 month 70, 58.3 and 90.9%
      were treated, respectively. This study shows that normal hips remain normal in
      nearly 100% of cases, but development to abnormality is possible. It shows also
      that most of the immature hips at the age of 1 month become normal without
      treatment. Although treatment seems to be indicated in the majority of
      sonographically abnormal hips, the occurrence of overtreatment could not be
      excluded in our study.

PMID- 16093943
TI  - The surgical treatment of teratologic dislocation of the hip.
AB  - Since 1974, our approach to treatment of teratologic dislocation of the hip in
      children has been surgical. We retrospectively reviewed 20 teratologic hip
      dislocations in 13 children with a minimum follow-up of 2 years. Closed treatment
      failed in most of the hips. At a mean age of 13 months, 11 patients (18 hips) had
      an open reduction and a one-and-a-half hip spica. It was followed in most of
      these hips by a femoral varus derotational osteotomy 6 weeks later. Only three
      hips had an open reduction followed by 3 months of casting. One of these three
      hips had salmonella infection and a redislocation. Our main complication was
      avascular necrosis in 20% of hips, two patients (two hips) ending with a leg
      length discrepancy. There was some limitation of motion in 65% of hips but 76% of
      patients had a good functional hip score. There was no difference in the results
      of unilateral versus bilateral dislocation. Poor results were found in three
      patients and could be explained by trunk hypotonia, marked limitation of motion
      and severe involvement of upper extremities, multiple deformities and fixed
      flexion in the lower extremities, generalized weakness and developmental delay.
      In spite of these difficulties and complications, results are encouraging.

PMID- 16093944
TI  - Length changes in tibial osteotomy with angular correction.
AB  - Twelve boys, aged 11-17 years, who underwent percutaneus proximal tibial
      osteotomy with acute angular correction and application of external fixator for
      unilateral Blount's disease were retrospectively reviewed. Preoperative
      radiographs were compared with radiographs at healing to evaluate changes in
      tibial length and overall limb length. Angular correction increased overall limb
      length by a mean of 1.4 cm (range -0.4 cm to 3.2 cm). This increase was a mean
      0.7 cm less than was predicted by adding the preoperative tibial and femoral
      lengths. This failure to achieve the predicted limb length occurs due to
      shortening in the tibia and should be considered when planning an osteotomy.

PMID- 16093945
TI  - Focal dome osteotomy for the correction of tibial deformity in children.
AB  - Tibial deformity in childhood often combines torsional and angular malalignment.
      A focal dome osteotomy was performed, proximally or distally, in 39 tibiae in 31
      patients. In 33 limbs, the primary deformity was varus (with internal torsion).
      The osteotomy was held with K-wires and a plaster cast. The mean age at surgery
      was 10.25 years and the minimum follow-up 24 months. All osteotomies united and
      no compartment syndrome occurred. Postoperatively, two patients (5%) had
      temporary neurological deficits. Thirty of 31 patients had good clinical and
      radiological correction of alignment. Recurrent deformity was seen in one patient
      with hypophosphataemic rickets.

PMID- 16093946
TI  - Ultrasound assessment of early clubfoot treatment: a comparison of the Ponseti
      method and a modified Copenhagen method.
AB  - The purpose of this study was to sonographically compare the early anatomical
      outcome of a group of clubfeet treated with the Ponseti method (group A, nine
      clubfeet) with a group treated with an adjustable plexidur splint, the Copenhagen
      method (group B, 19 feet). The clinical severity was assessed using the Dimeglio
      Bensahel classification. The need for complementary surgery was clinically
      assessed at the age of about 2 months. Ultrasound investigation was made in the
      neonatal period, after 2-3 months of non-surgical treatment and 1-2 months post
      surgically. After 2 months of non-surgical treatment the correction obtained at
      the talo-navicular joint, expressed as the distance between the medial malleolus
      and the navicular (MM-N distance), was significantly greater in group A. After
      surgery, tenotomy of the Achilles tendon for all group A feet, and posterior or
      posteriomedial release for 13 feet in group B, the correction at the talo
      navicular and calcaneo-cuboid joints was similar for the two groups. Anatomical
      correction of the displacement in these joints can be achieved without extensive
      interventional procedures. Ultrasound may be a valuable tool to assess the
      effects of different treatment protocols quantitatively.

PMID- 16093947
TI  - A comparison of resultant subtalar joint pathology with functional results in two
      groups of clubfoot patients treated with two different protocols.
AB  - Two series of patients with congenital clubfoot treated by different manipulation
      techniques and by different complementary soft tissue release operations were
      evaluated at the end of skeletal growth. The severity of the deformity was graded
      at diagnosis, and the functional results were graded at follow-up with a
      functional rating system. Computed tomography scans of the subtalar joint were
      also obtained at follow-up for each patient in order to evaluate the joint
      morphology. A linear regression model was constructed to study the statistical
      correlation between the rating score of the treated clubfeet and the shape of the
      subtalar joint. A statistically significant correlation was found between the
      clubfeet rating score and the subtalar joint morphology. However, the rating
      score values of the second series were consistently higher than those of the
      first series when compared with the same morphological category of the subtalar
      joint.

PMID- 16093948
TI  - Chronic osteomyelitis in children: Shriners Hospital Honolulu experience.
AB  - Chronic osteomyelitis incidence and severity in 55 hospitalized Pacific Island
      children between 1990 and 2002 were compared with the expected incidence and
      reports in the literature. Of these 55 cases, 87% were from Polynesia/Micronesia.
      The average length of hospital stay was 104 days. Staphylococcus aureus was
      cultured in 64% of the cases with 43% of those being methicillin resistant S.
      aureus. A total of 111 bones were involved. Average antibiotic treatment was 135
      days. Each case required an average of 1.3 irrigations/debridements and 45%
      required a sequestrectomy. Ninety-two percent had elevated erythrocyte
      sedimentation rate on admission. Sixty-nine percent of the cases involved
      metaphyseal, diaphyseal and epiphyseal segments of the bone and 29% were
      multifocal. Results indicate that Pacific Island children have a higher incidence
      and increased severity of osteomyelitis when compared with non-Pacific Island
      children in the literature, requiring a high suspicion for multifocal
      osteomyelitis, extensive bone involvement, S. aureus positive cultures and a
      longer period of antibiotic treatment.

PMID- 16093949
TI  - Percutaneous Ethibloc injection in the treatment of primary aneurysmal bone
      cysts.
AB  - The effects of percutaneous Ethibloc (Ethicon/Johnson & Johnson, St-Stevens
      Woluwe, Belgium) injection into primary aneurysmal bone cysts were analysed. Two
      patients with a venous drainage after injection of a medium contrast were
      excluded. Twelve patients underwent at least one percutaneous injection of
      Ethibloc. The average follow-up period was 5.1 years. At final follow-up, six
      patients had complete healing of the cyst, three had partial healing and three,
      who had no response, were treated by curettage and bone grafting. Complete
      healing was observed for all the aggressive lesions. No major complications were
      noted. Ethibloc injection may be performed as a primary treatment of aneurysmal
      bone cysts if the technique is followed with precision.

PMID- 16093950
TI  - Incidence study of nosocomial infection in pediatric trauma patients.
AB  - In this article we intend to describe the epidemiological profile of nosocomial
      infection in pediatric patients with multiple trauma. We conducted a prospective
      study from July to November 2003 in a pediatric teaching hospital in Barcelona.
      We used US Centers for Disease Control and Prevention standard criteria to define
      nosocomial infection. Of the 121 patients included in the study, 33% had at least
      one episode of nosocomial infection, with an incidence rate of 9.9 infections per
      100 admissions and 1.1 infections per 100 patient-days. The most frequent episode
      of nosocomial infection was bacteremia. Coagulase-negative staphylococci were the
      most common pathogens. Nosocomial infection rates per 100 device-days were 3.2
      for bacteremia, 1.6 for respiratory infection and 1.0 for urinary tract
      infection. These findings suggest the need to evaluate infection control measures
      aimed at reducing the morbidity associated with infections.

PMID- 16093951
TI  - Outcomes and complications of elastic stable intramedullary nailing for forearm
      fractures in children.
AB  - This prospective study investigated medium-term outcomes for 51 children treated
      from 1997 to 2001 for displaced diaphyseal forearm fractures with elastic stable
      intramedullary nailing. Forty-three patients included achieved excellent/good
      functional results at an average follow-up of 38 months. Four patients required
      open fracture-manipulation at surgery. Complications included eight cases of soft
      tissue irritation at nail-insertion site (three required shortening procedures),
      two temporary radial nerve branch injuries, four minimal rotational mobility
      deficits, one 10 degrees elbow extension deficit after splinting, and five small
      keloid scars. All patients were pain-free, without limitations in activities for
      daily life or sport/play activities by 12 months after hardware removal. Elastic
      stable intramedullary nailing is appropriate therapy for these injuries.

PMID- 16093952
TI  - Integra artificial skin in the management of severe tissue defects, including
      bone exposure, in injured children.
AB  - A dermal substitute, Integra (Integra Neurosciences Implants SA, Sophia
      Antipolis, France) artificial skin, was used for wound management on three
      children with lower limb injuries in our institutions. In one case this
      biosynthetic material was applied directly to a bony surface (patella). This
      technique allows an early wound coverage and provides a satisfactory preparation
      for autograft. It can be a useful adjunct in the treatment of severe tissue
      defects in child limb injuries.

PMID- 16093953
TI  - 'Wristlock restraint' and physeal injuries of the distal radius.
AB  - Wristlock is a commonly used physical restraining manoeuvre to control aggressive
      and violent persons in penal and medical institutions. We report three cases of
      similar physeal injuries to the distal radius sustained consequent to a wristlock
      restraint. There may be a higher morbidity involved when wristlock restraint is
      used on those with an immature skeleton. We recommend that caution must be
      exercised whenever a wristlock restraint is used on individuals under 16 years of
      age.

PMID- 16093958
TI  - Public education: the AUA and AUA foundation.

PMID- 16093959
TI  - The treatment of patients with bladder cancer: let's not forget the past!

PMID- 16093960
TI  - Assessing outcomes of hypospadias surgery.

PMID- 16093961
TI  - Urgency, botulinum toxin and how botulinum toxin can help urgency.

PMID- 16093962
TI  - siRNA for erectile dysfunction.

PMID- 16093963
TI  - In vivo models of prostate cancer metastasis to bone.
AB  - PURPOSE: The metastasis of prostate cancer to bone is the most significant cause
      of morbidity and mortality in this disease. An estimated 28,900 men die annually
      secondary to prostate cancer bone metastasis. Current treatments increase
      survival for 2 months and only bisphosphonates offer any palliative benefit. This
      shortcoming is due in part to inadequate models in which to study the molecular
      biology of the disease and evaluate therapeutic regimens. We examined the breadth
      of models available that recapitulate the process of prostate cancer metastasis
      to bone. MATERIALS AND METHODS: A PubMed search was done for publications
      concerning prostate cancer metastasis to bone and the imaging of bone metastases.
      Only studies focusing on model systems of disease progression and imaging of the
      process were included. Additional studies were found by cross-reference
      searching. RESULTS: Prostate cancer metastasis to bone is a lengthy, complex
      process characterized by multiple stages. This has made it difficult to find
      adequate laboratory models in which to recreate the disease process. Each
      available model has characteristics of particular phases of disease progression
      to bone. The most widely used models are transgenic mice, variations of SCID
      mice, and the traditional orthotopic and xenotransplantation models. Furthermore,
      investigators have started to adapt their models to incorporate imaging
      modalities for following the progression of prostate cancer to bone. CONCLUSIONS:
      The development of models of prostate cancer metastasis to bone is an evolving
      discipline. A deeper understanding of the metastatic process has served to
      improve current models and it will continue to do so in the future.

PMID- 16093964
TI  - Hypogonadism and metabolic syndrome: implications for testosterone therapy.
AB  - PURPOSE: Metabolic syndrome, characterized by central obesity, insulin
      resistance, dyslipidemia and hypertension, is highly prevalent in the United
      States. When left untreated, it significantly increases the risk of diabetes
      mellitus and cardiovascular disease. It has been suggested that hypogonadism may
      be an additional component of metabolic syndrome. This has potential implications
      for the treatment of metabolic syndrome with testosterone. We reviewed the
      available literature on metabolic syndrome and hypogonadism with a particular
      focus on testosterone therapy. MATERIALS AND METHODS: A comprehensive MEDLINE
      review of the world literature from 1988 to 2004 on hypogonadism, testosterone
      and metabolic syndrome was performed. RESULTS: Observational data suggest that
      metabolic syndrome is strongly associated with hypogonadism in men. Multiple
      interventional studies have shown that exogenous testosterone has a favorable
      impact on body mass, insulin secretion and sensitivity, lipid profile and blood
      pressure, which are the parameters most often disturbed in metabolic syndrome.
      CONCLUSIONS: Hypogonadism is likely a fundamental component of metabolic
      syndrome. Testosterone therapy may not only treat hypogonadism, but may also have
      tremendous potential to slow or halt the progression from metabolic syndrome to
      overt diabetes or cardiovascular disease via beneficial effects on insulin
      regulation, lipid profile and blood pressure. Furthermore, the use of
      testosterone to treat metabolic syndrome may also lead to the prevention of
      urological complications commonly associated with these chronic disease states,
      such as neurogenic bladder and erectile dysfunction. Physicians must be mindful
      to evaluate hypogonadism in all men diagnosed with metabolic syndrome as well as
      metabolic syndrome in all men diagnosed with hypogonadism. Future research in the
      form of randomized clinical trials should focus on further defining the role of
      testosterone for metabolic syndrome.

PMID- 16093965
TI  - Recruitment in pediatric clinical trials: an ethical perspective.
AB  - PURPOSE: There is a paucity of clinical trials in pediatric surgical disciplines.
      This is partly due to difficulties in recruiting participants. Frequently the
      origin of these problems lies in the ethical issues surrounding clinical trials
      in children. We reviewed the ethical barriers to recruitment in pediatric
      clinical trials and present recommendations to increase recruitment without
      violating accepted ethical boundaries. METHODS AND MATERIALS: A literature search
      using the MEDLINE, EMBASE and Google engines was performed. All available North
      American guidelines were reviewed. Guidelines at a major North American center
      were also reviewed as an example of institutional directives. RESULTS: Seven
      categories of ethical issues hampering recruitment were identified. The
      perspectives of different investigators are discussed as well as their
      recommended practical approaches to resolve the issues. CONCLUSIONS: Several
      recommendations are presented to help investigators enhance approval and
      recruitment rates in clinical trials involving children.

PMID- 16093966
TI  - Laparoscopic partial nephrectomy: comparison of transperitoneal and
      retroperitoneal approaches.
AB  - PURPOSE: Laparoscopic partial nephrectomy has become an effective alternative for
      small renal tumors. Previous reports include transperitoneal and retroperitoneal
      approaches but to our knowledge the indications for when to apply the techniques
      have not been defined. We report our experience with comparing the 2 techniques.
      MATERIALS AND METHODS: A retrospective review of 51 laparoscopic partial
      nephrectomies was performed. Patients were analyzed based on the surgical
      approach, operative parameters and postoperative recovery. The 2 approaches used
      similar operative techniques to control parenchymal bleeding and collecting
      system entry. RESULTS: There were 32 retroperitoneal and 19 transperitoneal
      partial nephrectomies. Mean operative time (3.5 vs 5.4 hours, p = 0.000001) and
      blood loss (192 vs 403 cc, p = 0.002) was significantly less for the
      retroperitoneal approach. Renal vessel clamping was performed in 81% of
      retroperitoneal and 63% of transperitoneal operations. Warm ischemia time was not
      significantly different between the groups. Patients undergoing the
      retroperitoneal approach had a statistically significant decrease in time to
      tolerating a regular diet (1.2 vs 1.7 days, p = 0.02), catheter removal (1.4 vs
      2.5 days, p = 0.004) and discharge home (2.3 vs 3.6 days, p = 0.0008).
      CONCLUSIONS: Based on tumor location as the selection criteria the
      retroperitoneal approach was associated with shorter operative time, less blood
      loss, more rapid return of bowel function and shorter hospitalization compared
      with those in patients selected for the transperitoneal technique. Based on our
      experience we believe that the decision on the approach should be based on the
      tumor location on the kidney surface. For polar or posterolateral masses the
      retroperitoneal approach is preferred. The transperitoneal approach is best
      suited to anterior and medial lesions.

PMID- 16093967
TI  - Transperitoneal versus retroperitoneal laparoscopic partial nephrectomy: patient
      selection and perioperative outcomes.
AB  - PURPOSE: We compared the results of transperitoneal (T) and retroperitoneal (R)
      approaches to laparoscopic partial nephrectomy (LPN) in regard to perioperative
      outcomes and technical considerations, thereby, identifying patient selection
      guidelines for each approach. MATERIALS AND METHODS: The choice of approach was
      dictated primarily by tumor location, that is TLPN for anterior or lateral
      lesions and RLPN for posterior or posterolateral lesions. The approaches differed
      primarily by the hilar control technique. During TLPN en bloc hilar control was
      achieved with a Satinsky clamp, while during RLPN individual vessel control was
      obtained with bulldog clamps. RESULTS: In a 3-year period 100 TLPNs and 63 RLPNs
      were performed for renal tumor. Of posterior tumors 77% were managed by RLPN,
      whereas 97% of anterior tumors were managed by TLPN. TLPN was associated with
      significantly larger tumors (3.2 vs 2.5 cm, p <0.001), more caliceal suture
      repairs (79% vs 57%, p = 0.004), longer ischemia time (31 vs 28 minutes, p =
      0.04), longer operative time (3.5 vs 2.9 hours, p <0.001) and longer hospital
      stay (2.9 vs 2.2 days, p <0.01) than RLPN. Blood loss, perioperative
      complications, postoperative serum creatinine, analgesic requirements and
      histological outcomes were comparable between the groups. CONCLUSIONS: We perform
      TLPN for all anterior or lateral tumors as well as for large or deeply
      infiltrating posterior tumors that require substantive resection
      (heminephrectomy). The limited retroperitoneal space makes RLPN technically more
      challenging but provides superior access to posterior and particularly
      posteromedial lesions. When feasible, we prefer to perform laparoscopic partial
      nephrectomy by the transperitoneal approach because of its larger working area
      and superior instrument angles for intracorporeal renal reconstruction.

PMID- 16093968
TI  - Laparoscopic partial nephrectomy for hilar tumors.
AB  - PURPOSE: Partial nephrectomy for hilar tumors represents a technical challenge
      not only for laparoscopic, but also for open surgeons. We report the technical
      feasibility and perioperative outcomes of laparoscopic partial nephrectomy (LPN)
      for hilar tumors. MATERIALS AND METHODS: Between January 2001 and September 2004,
      25 of 362 patients (6.9%) undergoing LPN for tumor, as performed by a single
      surgeon, had a hilar tumor. We defined hilar tumor as a tumor located in the
      renal hilum that was demonstrated to be in actual physical contact with the renal
      artery and/or renal vein on preoperative 3-dimensional computerized tomography.
      En bloc hilar clamping with cold excision of the tumor, including its delicate
      mobilization from the renal vessels, followed by sutured renal reconstruction was
      performed routinely. RESULTS: Laparoscopic surgery was successful in all cases
      without any open conversions or operative re-interventions. Mean tumor size was
      3.7 cm (range 1 to 10.3), 4 patients (16%) had a solitary kidney and the
      indication for LPN was imperative in 10 patients (40%). Pelvicaliceal repair was
      performed in 22 patients (88%), mean warm ischemia time was 36.4 minutes (range
      27 to 48), mean blood loss was 231 cc (range 50 to 900), mean total operative
      time was 3.6 hours (range 2 to 5) and mean hospital stay was 3.5 days (range 1.5
      to 6.7). Histopathology confirmed renal cell carcinoma in 17 patients (68%), of
      whom all had negative margins. In 2002 or earlier hemorrhagic complications
      occurred in 3 patients (12%). No kidney was lost for technical reasons.
      CONCLUSIONS: LPN can be performed in select patients with a hilar tumor. The
      technical feasibility reported further extends the scope of LPN. To our knowledge
      the initial experience in the literature is reported.

PMID- 16093969
TI  - Complications of contemporary open nephron sparing surgery: a single institution
      experience.
AB  - PURPOSE: Open nephron sparing surgery (NSS) is now the standard of care for small
      renal tumors irrespective of overall renal function. More recently laparoscopic
      NSS with hilar clamping has emerged, albeit with relatively longer ischemic
      times. We reviewed our experience with contemporary open NSS, comparing
      complication rates to those of historical controls and updating data for
      comparison with minimally invasive procedures. MATERIALS AND METHODS: From 1985
      to 2001, 823 open NSSs were performed at our institution. Early (within 30 days
      of NSS) and late (30 days to 1 year) complications were compared using the chi
      square and Wilcoxon rank sum tests between procedures performed in 1985 to 1995
      (control group of 343 patients) and 1996 to 2001 (contemporary group of 480).
      RESULTS: In the control vs the contemporary group there were significant
      decreases in intraoperative blood loss (median 550 vs 350 cc, p <0.001), chronic
      renal insufficiency/failure (14.6% vs 8.1%, p = 0.003), dialysis need (7.0% vs
      2.1%, p <0.001) and any early (13.4% vs 6.9%, p = 0.002) or late (32.4% vs 24.6%,
      p = 0.014) complication. In the contemporary group 50% of patients did not
      require pedicle clamping, 32% underwent warm ischemia (median 12 minutes) and 18%
      underwent cold ischemia (median 27 minutes). In addition, patients with a warm
      ischemia time of 20 minutes or less had fewer early complications than patients
      with greater than 20 minutes of ischemia, although this did not attain
      statistical significance (3.8% vs 13.6%, p = 0.063). CONCLUSIONS: Complications
      resulting from open NSS have significantly decreased with time. Contemporary open
      NSS is associated with minimal morbidity, and decreases the need for pedicle
      clamping and overall ischemia time.

PMID- 16093970
TI  - Multivariate analysis of clinical parameters of synchronous primary superficial
      bladder cancer and upper urinary tract tumor.
AB  - PURPOSE: We determined the incidence and characteristic of synchronous upper
      urinary tract tumors (UUTTs) in patients with primary superficial bladder
      carcinoma and evaluated the characteristics of bladder tumors related to UUTTs.
      MATERIALS AND METHODS: We performed a retrospective study of 1,529 patients with
      primary superficial bladder carcinoma who underwent initial examination of the
      upper urinary tract with excretory urography. Data were analyzed by multivariate
      analysis using logistic regression. Variables evaluated and related to the
      incidence of UUTT were multiplicity, carcinoma in situ, bladder tumor size,
      localization of tumor in the bladder, and tumor grade and stage. RESULTS: A total
      of 28 patients (1.8%) had simultaneous bladder tumor and UUTT. UUTTs showed no
      preferred location and 17.9% were multiple. Of UUTTs 46% were invasive and almost
      87% were grade 2 or 3. The only significant variable related to UUTT was bladder
      tumor in the trigone (RR 5.8, 95% IC 2.18 to 15.9, p <0.0005). Of 147 tumors
      located in the trigone 11 (7.5%) were associated with UUTT, corresponding to 41%
      of the UUTTs first diagnosed. If multiplicity and tumors in the trigone (551
      cases) had been considered, 66.7% of tumors would have been diagnosed.
      CONCLUSIONS: Synchronous UUTT and superficial bladder tumor are uncommon but 46%
      are invasive. Considering the possible examination of the upper urinary tract
      only in patients with tumor in the trigone or with multiple bladder tumors 41.4%
      or 69% of UUTTs, respectively, would have been diagnosed. Patients with tumor in
      the trigone are at almost 6-fold higher risk for a synchronous tumor in the upper
      urinary tract.

PMID- 16093971
TI  - Improved detection and treatment of bladder cancer using hexaminolevulinate
      imaging: a prospective, phase III multicenter study.
AB  - PURPOSE: We determined if improved tumor detection using hexaminolevulinate (HAL)
      fluorescence cystoscopy could lead to improved treatment in patients with bladder
      cancer. MATERIALS AND METHODS: A total of 146 patients with known or suspected
      bladder cancer were assessed in this open, comparative, within patient,
      controlled phase III study. Patients received intravesical HAL for 1 hour and
      were assessed with standard white light cystoscopy and blue light fluorescence
      cystoscopy. All lesions were mapped onto a bladder chart and biopsies were taken
      from suspicious areas for assessment by an independent pathologist. An
      independent urologist blinded to the detection method used recommended treatment
      plans based on biopsy results and medical history according to European
      Association of Urology bladder cancer guidelines. Any differences in recommended
      treatment plans arising from the 2 cystoscopy methods were recorded. RESULTS: HAL
      imaging improved overall tumor detection. Of all tumors 96% were detected with
      HAL imaging compared with 77% using standard cystoscopy. This difference was
      particularly noticeable for dysplasia (93% vs 48%), carcinoma in situ (95% vs
      68%) and superficial papillary tumors (96% vs 85%). As a result of improved
      detection, additional postoperative procedures were recommended in 15 patients
      (10%) and more extensive treatment was done intraoperatively in a further 10.
      Overall 17% of patients received more appropriate treatment at the time of the
      study following blue light fluorescence cystoscopy, that is 22% or 1 of 5 if
      patients without tumors were excluded. CONCLUSIONS: HAL imaging is more effective
      than standard white light cystoscopy for detecting bladder tumors and lesions.
      This leads to improved treatment in a significant number of patients (p <0.0001).

PMID- 16093972
TI  - Adrenal neoplasms: CT-guided radiofrequency ablation--preliminary results.

PMID- 16093973
TI  - Conservative management of incidental contrast-enhancing renal masses as safe
      alternative to invasive therapy.

PMID- 16093974
TI  - A renal mass in the setting of a nonrenal malignancy. When is a renal tumor
      biopsy appropriate?

PMID- 16093975
TI  - CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer.

PMID- 16093976
TI  - Minimally invasive therapy for renal cell carcinoma: is there a new community
      standard?

PMID- 16093977
TI  - Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10-enhanced
      MR imaging.

PMID- 16093978
TI  - Prostate specific antigen levels in young adulthood predict prostate cancer risk:
      results from a cohort of Black and White Americans.
AB  - PURPOSE: Prostate specific antigen (PSA) is a serine protease produced by normal
      and malignant prostate epithelial cells. Serum PSA increases with age, due
      largely to age related increases in the prevalence of benign prostatic disease.
      Little is known about PSA distribution in young adulthood, when benign and
      malignant prostatic diseases are rare, or about how PSA within the normal range
      in youth relates to subsequent prostate cancer risk. MATERIALS AND METHODS: We
      evaluated serum PSA and subsequent prostate cancer occurrence in a cohort of
      young black and white American men with a median age at blood draw of 34 years,
      who in 1959 to 1966 participated as the fathers of newborns enrolled in the Child
      Health and Development Study, and who were followed for several decades for
      prostate cancer. We examined associations between PSA in young adulthood and
      subsequent prostate cancer risk using a nested case-control design based on 119
      black and 206 white cases with 2 control men matched to each case on race and
      year of birth. RESULTS: Prostate cancer risk increased with increasing PSA in
      black and white men. The OR comparing risk in the highest to lowest quartiles of
      PSA was 4.4 (95% CI 2.0 to 9.6) in black men and 3.5 (95% CI 2.0 to 6.1) in white
      men. ORs relating risk to PSA were higher when analysis was restricted to cases
      diagnosed before age 65 years. CONCLUSIONS: These findings suggest that PSA
      levels in young adulthood indicate increased risk of prostate cancer and, thus,
      they may be useful for targeting men for screening and early diagnosis.

PMID- 16093979
TI  - Long-term effects of finasteride on prostate specific antigen levels: results
      from the prostate cancer prevention trial.
AB  - PURPOSE: Studies have shown that finasteride decreases prostate specific antigen
      (PSA) by approximately 50% during the first 12 months of use. We estimated the
      long-term effects of finasteride on PSA in men with and without a prostate cancer
      diagnosis at the end of the study. MATERIALS AND METHODS: We analyzed serial PSA
      in participants in the Prostate Cancer Prevention Trial who had an end of study
      biopsy (928 with cancer and 8,620 with negative biopsy) or an interim diagnosis
      of prostate cancer (671). Linear mixed effects regression models were fit to
      longitudinal PSA values beginning 1 year after randomization. RESULTS: In
      subjects with no cancer in the end of study biopsy PSA in the finasteride arm
      showed a median annual decrease of 2% [corrected] after year 1, while PSA in the
      control arm showed an annual increase of 3% (p <0.001). In end of study cases PSA
      increased annually by 6% (placebo) and 7% (finasteride). In those with interim
      diagnoses PSA increased by 11% (placebo) and 15% (finasteride) each year prior to
      diagnosis. Cases with high grade disease (Gleason 7 and above) had greater PSA
      increases than cases with low grade disease (p <0.001). CONCLUSIONS: In men who
      have been receiving finasteride for more than 1 year time varying adjustment
      factors may be needed to determine whether PSA is in the normal range. In the
      Prostate Cancer Prevention Trial cohort the adjustment factor required to
      preserve median PSA increased from 2 at 24 months to 2.5 at 7 years after the
      initiation of finasteride.

PMID- 16093980
TI  - A new model using number of needles and androgen deprivation to predict chronic
      urinary toxicity for high or low dose rate prostate brachytherapy.
AB  - PURPOSE: Prostate brachytherapy is an established treatment modality in early
      stage prostate cancer. We retrospectively reviewed our experience with low dose
      rate (LDR) and high dose rate (HDR) brachytherapy as a single treatment modality
      for early prostate cancer with emphasis on chronic toxicity. MATERIALS AND
      METHODS: From June 1996 to August 2003, 253 patients with stage II prostate
      cancer, prostate specific antigen less than 12 and Gleason score less than 7 were
      treated with brachytherapy alone at our institution. A total of 92 patients
      underwent HDR brachytherapy with 192Ir, while 161 underwent LDR brachytherapy
      with 103Pd. HDR minimum prostate dose was 38 Gy, delivered in 4 fractions with a
      single implant during 36 hours. For HDR we used real-time dynamic 3-dimensional
      ultrasound base dosimetry. For 103Pd seed implants the dose was 120 Gy using
      selective peripheral weighted dose distribution. Treatment was given based on
      patient preference after pretreatment transrectal ultrasound. Toxicity was scored
      using the National Cancer Institute Common Toxicity Criteria 2.0. Median followup
      in all 253 cases was 2.9 years. RESULTS: In all patients the rate of 3-year
      urinary toxicity grade 2 or greater and grade 3 or greater was 26% and 6.9%,
      which was not significantly different between HDR and LDR (p = 0.3 and 0.4,
      respectively). However, grade 1 urogenital toxicity was lower for HDR (p =
      0.002). The 3-year grade 2 rectal toxicity rate was 0.8% with no grade 3 or
      greater events, which was and similar in the HDR and LDR groups (1% and 0.6%,
      respectively). No cancer related deaths occurred and 4-year overall survival was
      99% for HDR and 96.4% for LDR (p = 0.4). The 3-year American Society for
      Therapeutic Radiology and Oncology biochemical control rate was 90% for LDR and
      93% for HDR. Cox multivariate analysis for grade 2 or greater urinary toxicity
      was significant for the use of 14 or greater needles (HR 6.1, p = 0.02) and
      hormonal therapy (HR 2.2, p = 0.02). In the absence of risk factors the 4-year
      grade 2 or greater urinary toxicity rate was 7% vs 65% if the 2 risk factors were
      present (p <0.001). Impotence crude rates were 18.3% for HDR and 41.3% for LDR (p
      = 0.002). CONCLUSIONS: HDR and LDR chronic urinary toxicity grade 2 or greater
      rates were equivalent. However, grade 1 was lower for HDR. The impotence rate was
      decrease by half with HDR. Neoadjuvant hormonal therapy and 14 or greater needles
      were significantly associated with increased chronic urinary toxicity on
      multivariate analysis.

PMID- 16093981
TI  - High dose pulse calcitriol, docetaxel and estramustine for androgen independent
      prostate cancer: a phase I/II study.
AB  - PURPOSE: We determined the safety and preliminary efficacy of the combination of
      high dose pulse calcitriol (1,25-dihydroxycholecalciferol) with a standard
      regimen of docetaxel plus estramustine in patients with metastatic androgen
      independent prostate cancer. MATERIALS AND METHODS: Patients were treated with 60
      microg calcitriol orally on day 1, 280 mg estramustine orally 3 times daily on
      days 1 to 5 and 60 mg/m docetaxel on day 2 (70 mg/m after cycle 1) every 21 days
      for up to 12 cycles. Patients also received 325 mg aspirin and 1 or 2 mg warfarin
      orally daily. Regimen safety was assessed in the first 6 patients and a dose de
      escalation scheme for calcitriol was planned if dose limiting toxicities were
      noted during treatment cycle 1 in greater than a third of patients. RESULTS: A
      total of 24 patients, including 11 who were chemotherapy naive and 13 who had
      previously been treated with docetaxel, were evaluable for toxicity and 22 for
      prostate specific antigen decrease data. The regimen was generally well
      tolerated. Treatment related grades 3 or greater toxicity seen in more than 1
      patient included hypophosphatemia in 16.7% and neutropenia in 12.5%. Four
      patients had thromboembolic complications. Asymptomatic hypercalcemia was seen in
      4 patients, including grades 2 and 1 in 1 and 3, respectively. Six of 11
      evaluable, chemotherapy naive patients (55%) met prostate specific antigen
      response criteria. One of 11 patients (9%) treated with prior docetaxel met these
      criteria. CONCLUSIONS: High dose calcitriol may be safely added to docetaxel and
      estramustine administered on a 21-day schedule.

PMID- 16093982
TI  - Epididymal sparing bilateral simple orchiectomy with epididymoplasty:
      preservation of esthetics and body image.
AB  - PURPOSE: We report the surgical technique and results of epididymal sparing
      bilateral simple orchiectomy as an esthetic alternative to standard bilateral
      simple orchiectomy and luteinizing hormone releasing hormone (LH-RH) agonist
      injection therapy in patients with prostate cancer. MATERIALS AND METHODS: The
      study included 91 consecutive epididymal sparing bilateral simple orchiectomy
      (BSO) procedures that were performed at the Atlanta Veterans Affairs Medical
      Center during a 25-month period. All patients had pathologically confirmed
      prostate cancer. A total of 52 patients (57.1%) were receiving LH-RH agonist
      therapy prior to the procedure and the remaining 39 (42.9%) were not. All
      procedures were performed in an outpatient clinic setting using spermatic cord
      anesthesia block as the only method of anesthesia. In the 52 patients who were on
      LH-RH agonist therapy prior to the procedure the overall impression/satisfaction
      with the procedure was evaluated using a questionnaire. RESULTS: All 91
      procedures were performed at the urology outpatient clinic using local
      anesthesia. Mean patient age was 74.2 years (range 44 to 86). Mean serum prostate
      specific antigen was 58.9 ng/ml. The mean time required to perform the spermatic
      cord anesthesia block was 3.9 minutes (range 2 to 6) and the volume of anesthetic
      solution was 18.9 ml per case (range 10 to 32). Despite significant difference in
      testicular size between patients receiving and not receiving LH/RH agonists there
      were no differences in anesthesia time or anesthetic volume (3.9 and 3.9 minutes,
      p = 0.97, and 18.6 and 19.4 ml, respectively, p = 0.47). Mean operative time for
      BSO excluding anesthesia time was 36.9 minutes (range 18 to 70). Mean operative
      time was similar in patients receiving and not receiving LH-RH agonists (36.2 and
      37.8 minutes, respectively, p = 0.39). The procedure was well tolerated, as
      judged by the mean intraoperative pain score during BSO of 0.2 (range 0 to 3).
      The majority of patients (76 or 83.5%) were pain-free during the procedure. Pain
      scores were similar in patients who were and were not receiving LH-RH agonists
      during BSO (p = 0.97). There were no adverse events. Followup data were available
      on 26 of the 52 patients who were receiving LH-RH agonist therapy prior to the
      procedure. Of them 96.2% were satisfied with the results and 84.6% preferred the
      procedure over medical castration therapy with LH-RH agonist therapy.
      CONCLUSIONS: Epididymal sparing bilateral simple orchiectomy is a simple and safe
      procedure that can be conveniently performed in an outpatient clinic setting
      using pure local anesthesia. Preservation of the epididymis and subsequent
      epididymoplasty is effective for maintaining the esthetic appearance of the
      scrotum and patient satisfaction. The procedure offers patients the convenience
      of 1-time surgical therapy over lifelong medical injection therapy at a
      significantly lower cost and without significantly compromising the esthetic
      appearance of the scrotum.

PMID- 16093983
TI  - Preoperative prediction of small volume cancer (less than 0.5 ml) in radical
      prostatectomy specimens.
AB  - PURPOSE: The detection of low volume and early stage prostate cancer has
      increased with the widespread use of prostate specific antigen screening for
      prostatic adenocarcinoma. This increased detection has led to efforts to stratify
      patient risk and the potential benefits of various treatments based on
      preoperative clinical and biopsy data. We examined various clinical parameters
      and prostate biopsy features to determine which variables are most predictive of
      small volume (less than 0.5 ml) cancer at prostatectomy. MATERIALS AND METHODS:
      We studied 336 patients who underwent prostatectomy for prostate cancer. Radical
      prostatectomy specimens were completely embedded and whole mounted. Final tumor
      volume in the radical prostatectomy specimens was determined by the grid method.
      Clinical data were gathered by a review of patient charts. Various preoperative
      clinical and biopsy findings were analyzed to determine factors predictive of
      small volume cancer at prostatectomy. RESULTS: A total of 55 patients (16%) were
      found to have small volume cancer (less than 0.5 ml). On univariate logistic
      regression certain variables were significant predictors of small volume cancer,
      namely the highest Gleason score from all positive biopsy sites (p = 0.001), the
      Gleason score from the biopsy site with the highest percent of adenocarcinoma (p
      = 0.006), the highest percent of adenocarcinoma at any biopsy site (p <0.0001),
      the percent of adenocarcinoma at the biopsy site with the highest Gleason score
      (p <0.0001), the highest percent of cores positive for adenocarcinoma at any
      biopsy site (p = 0.001), the percent of cores with carcinoma at the site with the
      highest Gleason score (p = 0.002), the number of positive sites (p <0.0001) and
      tumor bilaterality (p <0.0001). None of the clinical parameters that we studied,
      including preoperative prostate specific antigen (p = 0.52), clinical stage (p =
      0.62) or patient age (p = 0.94), was predictive of small volume cancer. On
      multivariate analysis the highest percent of adenocarcinoma at any site (adjusted
      OR 0.95, 95% CI 0.92 to 0.97, p <0.0001) and the number of positive biopsy sites
      (adjusted OR 0.97, 95% CI 0.96 to 0.99, p <0.0001) were significant predictors of
      small volume cancer. CONCLUSIONS: The number of positive biopsy sites and the
      highest percent of adenocarcinoma at any biopsy site are significant predictors
      of small volume cancer in radical prostatectomy specimens.

PMID- 16093984
TI  - Do margins matter? The prognostic significance of positive surgical margins in
      radical prostatectomy specimens.
AB  - PURPOSE: The prognostic significance of positive surgical margins (PSM) in
      radical prostatectomy (RP) specimens remains unclear. While most studies have
      concluded that a PSM is an independent adverse prognostic factor, others report
      that surgical margin status has no effect on prognosis. One reason for these
      discordant conclusions is the variable number of patients with a PSM who receive
      adjuvant therapy and the differing statistical methods used to account for the
      effects of the time course of adjuvant treatment on recurrence. We evaluated the
      prognostic significance of PSMs using multiple methods of analysis accounting for
      patients who received adjuvant therapy. MATERIALS AND METHODS: We analyzed 1,389
      consecutive patients with clinical stage T1-3 prostate cancer treated with RP by
      2 surgeons from 1983 to 2000. Of 179 patients with a PSM, 37 received adjuvant
      therapy (AT), 29 radiation therapy and 8 received hormonal therapy. Because the
      method used to account for men receiving AT can affect the outcome of the
      analysis, data were analyzed by the Cox proportional hazards technique accounting
      for patients receiving AT using 5 methods: 1) exclusion, 2) inclusion (AT
      ignored), 3) censoring at time of AT, 4) failing at time of AT and 5) considering
      AT as a time dependent covariate. RESULTS: Overall 179 patients (12.9%) had a
      PSM, including 6.8% of 847 patients with pT2 and 23% of 522 patients with pT3
      disease. A PSM was a significant predictor of cancer recurrence when analyzed
      using methods 1, 3, 4 and 5 (p=0.005, p=0.014, p=0.0005, p=0.002, respectively).
      However, it was not a predictor of recurrence using method 2 in which AT was
      ignored (p=0.283). Using method 5 multivariate analysis demonstrated that a PSM
      (p=0.002) was an independent predictor of 10-year progression-free probability
      (PFP) along with Gleason score (p=0.0005), extracapsular extension (p=0.0005),
      seminal vesicle invasion (p <0.0005), positive lymph nodes (p <0.0005) and
      preoperative serum prostate specific antigen (p <0.0001). Using method 5 the 10
      year PFP was 58% +/- 12% and 81% +/- 3% for patients with and without a PSM,
      respectively (p <0.00005). The relative risk of recurrence in men with a PSM
      using method 5 was 1.52 (95% confidence interval 1.06-2.16). CONCLUSIONS: We
      confirm that a PSM has a significant adverse impact on PFP after RP in
      multivariate analysis using multiple statistical methods to account for patients
      who received AT. While prostate cancer screening strategies have resulted in a
      majority of men having organ confined disease at RP, surgeons should continue to
      strive to reduce the rate of positive surgical margins to improve cancer control
      outcomes.

PMID- 16093985
TI  - Extraperitoneal laparoscopic radical prostatectomy: a prospective evaluation of
      600 cases.
AB  - PURPOSE: We report our experience with the extraperitoneal approach to
      laparoscopic radical prostatectomy. We describe the technique, clinical and
      oncological results, and functional outcome. MATERIALS AND METHODS: From February
      2002, to March 2004, 600 laparoscopic radical prostatectomies were performed by
      an extraperitoneal approach and evaluated prospectively. RESULTS: A total of 599
      extraperitoneal procedures were performed successfully. Mean operative time was
      173 minutes. Mean operative blood loss was 380 cc. The transfusion rate was 1.2%.
      The major and minor complications rate was 2.3% and 9.2%, respectively. The
      reoperation rate was 1.7%. Mean hospital stay was 6.3 days. Pathological stage
      was pT2 and pT3 in 72% and 28% of cases, respectively. Mean Gleason score was 7.
      The overall positive margin rate was 17.7% (14.6% and 25.6% of pT2 and pT3
      tumors, respectively). Median followup was 12 months. Of the patients 95% had
      prostate specific antigen less than 0.2 ng/ml. Patients were evaluated by a self
      questionnaire sent by mail before and after surgery (International Continence
      Society and International Index of Erectile Function-5). At a median followup of
      12 months 84% of the patients were continent (no pad), 7% used 1 precautionary
      pad and 7% needed 1 pad routinely. At a median followup of 6 months in
      preoperatively potent patients (International Index of Erectile Function-5
      greater than 20) the postoperative erection and intercourse rate was 64% and 43%,
      respectively, in those with bilateral nerve bundle preservation. CONCLUSIONS: The
      extraperitoneal technique is a reliable approach to laparoscopic radical
      prostatectomy.

PMID- 16093986
TI  - Robotic assisted laparoscopic radical prostatectomy versus retropubic radical
      prostatectomy: a prospective assessment of postoperative pain.
AB  - PURPOSE: Laparoscopic prostatectomy, whether or not coupled with robotic
      assistance, is often considered less invasive than open radical retropubic
      prostatectomy (RRP). Minimal postoperative pain has been reported following robot
      assisted laparoscopic prostatectomy (RALP) but there have been few comparative
      studies with RRP. We compared perioperative narcotic use and patient reported
      pain in a prospective patient series. MATERIALS AND METHODS: Between June 2003
      and May 2004, 314 patients underwent radical prostatectomy at our institution,
      including RALP in 159, RRP in 154 and conversion in 1. All patients were treated
      on a postoperative clinical pathway that included 30 mg ketorolac intravenously
      immediately postoperatively, followed by 15 mg intravenously every 6 hours. No
      regional anesthesia (epidural/spinal) narcotics or patient controlled analgesic
      pumps were used. All narcotic use was converted to morphine sulfate equivalents
      for purpose of analysis. A Likert scale of 0 to 10 was used to assess pain on the
      day of surgery, and on postoperative days 1 and 14. RESULTS: The total mean
      morphine sulfate equivalent +/- SD in patients in the RALP and RRP groups was low
      and, when corrected for length of stay, it was not statistically different (22.41
      +/- 1.13 vs 23.01 +/- 1.16 mg, p = 0.72). Mean Likert pain perception scores were
      low at all time points in the RALP and RRP groups but statistically lower on the
      day of surgery in the RALP cohort (2.05 +/- 1.99 vs 2.60 +/- 2.25, p = 0.027).
      Patient reported mean pain scores were almost identical for RALP vs RRP on
      postoperative days 1 (1.76 +/- 1.87 vs 1.73 +/- 1.77, p = 0.880) and 14 (2.51 +/-
      1.91 vs 2.42 +/- 1.84, p = 0.722). CONCLUSIONS: Perioperative narcotic use and
      patient reported pain are low regardless of the surgical approach used for
      radical prostatectomy. RALP did not provide a clinically meaningful decrease in
      pain compared with RRP, primarily because of the low pain scores reported in each
      group. Outcomes other than pain will ultimately determine the role of
      laparoscopic radical prostatectomy and RALP.

PMID- 16093987
TI  - Perioperative complications of robotic radical prostatectomy after the learning
      curve.
AB  - PURPOSE: We assessed the incidence of and analyzed factors that contributed to
      perioperative complications in patients undergoing robotic radical prostatectomy,
      that is Vattikuti Institute prostatectomy (VIP), at our institution. MATERIALS
      AND METHODS: We recorded operative and postoperative data on 300 consecutive
      patients who underwent VIP at our institution during a 1-year period. All
      operations were performed by 1 of 2 surgeons (MM or JOP). We reviewed the
      complications seen in these patients. RESULTS: There was no operative mortality
      and no case was converted to open surgery. A total of 269 (89.7%) patients were
      considered to have an ideal postoperative course, ie they were discharged home
      within 48 hours with no unscheduled office visits or complications. There were 14
      unscheduled postoperative visits (4.7%) for transient urinary retention after
      early catheter removal (13) or hematuria (1). There were 17 complications, of
      which 16 (5.3%) were related to surgery and 1 was related to anesthesia. A total
      of 11 complications (3.7%) were minor (grade I) and 5 (1.7%) were major (grade
      II). Of them 3 (1%) patients required reoperation. There were no grade III or IV
      complications. CONCLUSIONS: In our hands VIP is a safe operation with an overall
      complication rate of 5.3%, a major complication rate of less than 2% and a
      surgical re-intervention rate of 1%.

PMID- 16093988
TI  - Obesity and risk of biochemical progression following radical prostatectomy at a
      tertiary care referral center.
AB  - PURPOSE: We have previously reported that obesity is an independent predictor of
      biochemical progression after radical prostatectomy (RP) in men treated by a
      single surgeon at our institution. We sought to validate or refute these findings
      using data on men treated by multiple other surgeons at our institution.
      MATERIALS AND METHODS: The study population consisted of 2,796 men treated with
      anatomical radical RP between 1988 and 2004 by 1 of 17 surgeons at our
      institution, a tertiary care referral center. We evaluated the association
      between body mass index (BMI), and adverse pathological features and biochemical
      progression. RESULTS: On multivariate analysis increased BMI was associated with
      high grade disease in the RP specimen (p = 0.03), positive surgical margins (p
      <0.001), extraprostatic extension (p <0.001) and lymph node metastasis (p = 0.01)
      but not with seminal vesicle invasion (p = 0.59). After multivariate adjustment
      for preoperative clinical characteristics increased BMI was significantly
      associated with an increased risk of biochemical progression (p <0.001), which
      was somewhat but not completely attenuated by further adjusting for RP specimen
      pathological features (p = 0.03). Adjustment for surgeon did not affect these
      results. CONCLUSIONS: In men undergoing RP increased BMI was associated with
      adverse pathological features and a greater risk of biochemical progression.
      These findings together with the results of several recently published series
      collectively provide strong evidence that obese men undergoing RP are more likely
      to have aggressive prostate cancer.

PMID- 16093990
TI  - Failure definition-dependent differences in outcome following radiation for
      localized prostate cancer: can one size fit all?

PMID- 16093989
TI  - Regional lymph node staging using lymphotropic nanoparticle enhanced magnetic
      resonance imaging with ferumoxtran-10 in patients with penile cancer.
AB  - PURPOSE: We evaluated lymphotropic nanoparticle enhanced magnetic resonance
      imaging (LNMRI) with ferumoxtran-10 in determining the presence of regional lymph
      node metastases in patients with penile cancer. MATERIALS AND METHODS: Seven
      patients with squamous cell carcinoma of the penis underwent LNMRI. All patients
      subsequently underwent groin dissection and the nodal images were correlated with
      histology. RESULTS: We found that LNMRI had sensitivity, specificity, and
      positive and negative predictive values of 100%, 97%, 81.2% and 100%,
      respectively, in predicting the presence of regional lymph node metastases in
      patients with penile cancer. CONCLUSIONS: Lymph node scanning using LNMRI
      accurately predicts the pathological status of regional lymph nodes in patients
      with cancer of the penis. LNMRI may accurately triage patients for regional
      lymphadenectomy.

PMID- 16093991
TI  - Risk of fracture after androgen deprivation for prostate cancer.

PMID- 16093992
TI  - Immediate versus deferred hormonal treatment for patients with prostate cancer
      who are not suitable for curative local treatment: results of the randomized
      trial SAKK 08/88.

PMID- 16093993
TI  - Lateral pedicle control during laparoscopic radical prostatectomy: refined
      technique.

PMID- 16093994
TI  - Differential regulation of p21waf-1/cip-1 and Mdm2 by etoposide: etoposide
      inhibits the p53-Mdm2 autoregulatory feedback loop.

PMID- 16093995
TI  - General versus spinal anesthesia in patients undergoing radical retropubic
      prostatectomy: results of a prospective, randomized study.

PMID- 16093996
TI  - A double-blind, placebo controlled comparison of the morphine sparing effect of
      oral rofecoxib and diclofenac for acute renal colic.
AB  - PURPOSE: We compared the morphine sparing effect of a single dose of 50 mg oral
      rofecoxib, 3, 8-hourly doses of 50 mg diclofenac and placebo for acute renal
      colic. MATERIALS AND METHODS: Patients who were 18 to 69 years old with
      clinically diagnosed acute renal colic and a visual analog scale (VAS) score of
      40 mm or greater at hospital admission were randomized to receive 1 of the 3
      treatment regimens, delivered in 3 identical encapsulated tablets. The primary
      end point was the mean total amount of intravenously administered morphine in the
      24 hours following study medication dose 1. Secondary end points were mean VAS
      score and the number of treatment withdrawals due to pain. RESULTS: Of 400
      patients admitted with acute flank pain 225 fulfilled the inclusion criteria, of
      whom 110 (49%) were eligible for evaluation and received rofecoxib (36),
      diclofenac (39) and placebo (35). Baseline characteristics in the 3 groups did
      not differ. Intent to treat analysis showed that mean morphine consumption was
      13.6 mg in the rofecoxib group (95% CI 10.3 to 16.9), 10.2 mg in the diclofenac
      group (95% CI 7.7 to 12.7) and 11.5 mg in the placebo group (95% CI 8.8 to 14.3).
      The differences were not significant (p = 0.23). The same applied to mean VAS
      scores in the 3 groups (p = 0.22). There were no differences in the number of
      pain related treatment withdrawals (p = 0.64). CONCLUSIONS: No clinically
      relevant morphine sparing effect was seen in patients with renal colic treated
      with 50 mg oral diclofenac every 8 hours or a single dose of 50 mg rofecoxib as a
      representative of the specific inhibitors of cyclooxygenase-2.

PMID- 16093997
TI  - Risk of irritable bowel syndrome and depression in women with interstitial
      cystitis: a case-control study.
AB  - PURPOSE: We determined the risk of irritable bowel syndrome and depression in
      women with interstitial cystitis. MATERIALS AND METHODS: Cases consisted of 46
      women with newly diagnosed interstitial cystitis. The control group consisted of
      46 women presenting for an annual gynecologic examination. Data were collected
      using standardized, validated questionnaires. RESULTS: The 2 groups were similar
      with respect to age, race, parity, previous pelvic surgery and postmenopausal
      hormone use. Compared with controls patients with interstitial cystitis were more
      likely to be diagnosed with irritable bowel syndrome (OR 11, 95% CI 2.7 to 52, p
      <0.001) and depression (OR 3.97, 95% CI 1.17 to 14.1, p <0.05). In the
      interstitial cystitis group when we compared women with and without depression,
      we noted that women with depression were significantly more likely to complain of
      bladder pain, nocturia, abdominal pain and other bowel symptoms. CONCLUSIONS: The
      association of irritable bowel syndrome and depression appears to be greater in
      women with interstitial cystitis than in controls. Additionally, it appears that
      pain of bladder or bowel origin is a significant cause of depression in women
      with interstitial cystitis.

PMID- 16093998
TI  - The urine dipstick test useful to rule out infections. A meta-analysis of the
      accuracy.

PMID- 16093999
TI  - Urinary tract infection in the users of depot-medroxyprogesterone acetate.

PMID- 16094000
TI  - Selective urological evaluation in men with febrile urinary tract infection.

PMID- 16094001
TI  - Urologic myofascial pain syndromes.

PMID- 16094002
TI  - Dietary oxalate loads and renal oxalate handling.
AB  - PURPOSE: Dietary oxalate makes a significant contribution to urinary oxalate
      excretion and, thus, may have a role in calcium oxalate kidney stone formation.
      Studies have indicated that the ingestion of oxalate rich foods results in
      transient increases in plasma oxalate concentrations and urinary oxalate
      excretion. We examined changes in plasma and urinary oxalate following oral
      crystalline oxalate loading under controlled dietary conditions to further define
      the renal handling of oxalate by normal adults. MATERIALS AND METHODS: Six normal
      adult subjects consumed controlled diets of known oxalate content for 1 week
      before ingesting loads of 0, 2, 4 and 8 mmol of oxalate. Urinary and plasma
      changes were measured to assess renal oxalate handling. Urinary excretion of
      proximal tubule derived enzymes and isoprostanes was monitored to assess for
      renal injury and oxidative stress. RESULTS: Time and dose dependent changes in
      plasma oxalate, urinary oxalate and in the clearance ratio of oxalate-to
      creatinine were observed. A significant correlation (r=0.43, p <0.001) between
      the oxalate-to-creatinine clearance ratio and plasma oxalate levels was
      identified. No changes in urinary markers of oxidative stress or renal injury
      were observed following the 8 mmol oxalate load. CONCLUSIONS: Oxalate is rapidly
      absorbed and cleared by the kidney by filtration and secretion following an oral
      oxalate load. Renal oxalate secretion has a significant role in the renal
      handling of an oral oxalate load. There is no evidence of acute renal injury or
      oxidative stress with oral oxalate loads in these experimental conditions.

PMID- 16094003
TI  - Radiation exposure and the urologist: what are the risks?
AB  - PURPOSE: Endourology is established in urology practice with routine use of
      fluoroscopic guidance. Medical personnel are rarely exposed to direct radiation
      exposure but secondary exposure occurs via radiation scatter. There are few
      reports on scatter radiation exposure and the subsequent risk to medical
      personnel involved in urological fluoroscopic procedures. We review the risks of
      scatter radiation exposure to medical personnel with reference to the routine use
      of fluoroscopic imaging in urological practice. MATERIALS AND METHODS: We
      measured staff radiation exposure during a series of ureteral endourological
      procedures using LiF:Mg,Ti thermoluminescent dosimeters placed at the extremities
      of the operating surgeon, the assistant and the scrub nurse. Doses for
      percutaneous nephrolithotomy (PCNL) procedures were calculated by extrapolating
      from the ureteral procedure thermoluminescent dosimeter data. Theoretical
      scattered radiation dose rates were also calculated. RESULTS: The average
      ureteral procedure fluoroscopy time was 78 seconds with an exposure rate of 71
      kV, 2.4 mA. The surgeon received the highest radiation exposure with the lower
      leg (11.6 +/- 2.7 microGy) and foot (6.4 +/- 1.8 microGy) receiving more
      radiation than the eyes (1.9 +/- 0.5 microGy) and hands (2.7 +/- 0.7 microGy).
      For a predicted annual caseload of 50 ureteral cases, the dose received does not
      exceed 0.12% of the Ionising Radiations Regulations 1999 annual dose limit for
      adult workers. Radiation exposure during PCNLs is higher but does not exceed 2%
      of the annual dose limits even if 50 PCNLs are performed annually. CONCLUSIONS:
      Fluoroscopic screening results in radiation exposure of medical personnel. The
      estimate of maximum scatter radiation exposure to the surgeon for 50 PCNL
      procedures a year did not exceed 10 mGy. This amount is less than 2% of
      permissible annual limits of equivalent dose to the extremities. Medical
      personnel should be aware of scatter radiation risks and minimize radiation
      exposure when involved in fluoroscopic screening procedures.

PMID- 16094004
TI  - Minimally invasive surgery for pelviureteral junction obstruction in adults: a
      critical review of the options.

PMID- 16094005
TI  - Surgical robotics: impact of motion scaling on task performance.

PMID- 16094006
TI  - Ureteropelvic junction obstruction: does CT angiography allow better selection of
      therapeutic modalities and better patient outcome?

PMID- 16094007
TI  - Bulbar urethroplasty using buccal mucosa grafts placed on the ventral, dorsal or
      lateral surface of the urethra: are results affected by the surgical technique?
AB  - PURPOSE: The use of buccal mucosa graft onlay urethroplasty represents the most
      widespread method of bulbar urethral stricture repair. The graft may be placed on
      the ventral or dorsal urethral surface according to surgeon experience and
      preference. We investigated whether the results are affected by the surgical
      technique by comparing the outcome of 3 types of bulbar urethroplasty using
      buccal mucosa graft. MATERIAL AND METHODS: We repaired 50 bulbar urethral
      strictures with buccal mucosa grafts from 1997 to 2002. Mean patient age was 42
      years. The etiology of stricture was ischemia in 12 cases, trauma in 6,
      instrumentation in 4 and unknown in 28. Patients with lichen sclerosus, failed
      hypospadias or urethroplasty and stricture extending into the penile urethra were
      not included. A total of 47 patients (94%) had undergone previous urethrotomy or
      dilation. The buccal mucosa graft was always harvested from the cheek using a 2
      team approach. Mean graft length was 4.2 cm. The graft was placed on the ventral,
      dorsal and lateral bulbar urethral surface in 17, 27 and 6 cases, respectively.
      Clinical outcome was considered a success or failure at the time that any
      postoperative procedure was needed, including dilation. Mean followup was 42
      months (range 12 to 76). RESULTS: Of 50 cases 42 (84%) were successful and 8
      (16%) failed. The 17 ventral grafts provided success in 14 cases (83%) and
      failure in 3 (17%). The 27 dorsal grafts provided success in 23 cases (85%) and
      failure in 4 (15%). The 6 lateral grafts provided success in 5 cases (83%) and
      failure in 1 (17%). No surgical complications were observed. Failures involved
      the anastomotic site (distal in 2 and proximal in 3) and the whole grafted area
      in 3 cases. They were treated with urethrotomy in 5 cases and 2-stage
      urethroplasty in 3. CONCLUSIONS: In our experience the placement of buccal mucosa
      grafts into the ventral, dorsal or lateral surface of the bulbar urethra showed
      the same success rates (83% to 85%) and the outcome was not affected by the
      surgical technique. Moreover, stricture recurrence was uniformly distributed in
      all patients.

PMID- 16094008
TI  - The anterior ileal conduit: results of 100 consecutive cases.
AB  - PURPOSE: The ileal conduit of Bricker is still widely used for urinary diversion
      after radical cystectomy for bladder carcinoma. We have modified the standard
      technique with the aim of reducing the complication rate and facilitating
      treatment. MATERIALS AND METHODS: We leave the conduit in its natural
      isoperistaltic anterior position, the ureters are anastomosed in an anterior
      position on their own side, using a short ileum segment. The incision of the
      peritoneum is made in a particular manner to allow on its closure to
      extraperitonealize the anastomoses and the bottom of the conduit and to support
      and fasten the loop. RESULTS: A total of 100 consecutive patients after radical
      cystectomy for bladder cancer had anterior ileal conduit. The complication rates
      were 5% temporary ureteroileal leakage, 1% reoperation rate, 5% long-term
      stenoses and 3% renal function deterioration. The surgical revision and the
      treatment of ureteroileal stenoses with anterograde percutaneous ureteral
      stenting were not complicated procedures. A comparison with conventional Bricker
      series shows a significant decrease in the complication rate. CONCLUSIONS: The
      anterior ileal conduit reduces the technique complication rate and facilitates
      the treatment of complications, and it is a recommended operation for these
      reasons.

PMID- 16094009
TI  - Long-term functional and urodynamic results of 50 patients receiving a modified
      sigmoid neobladder created with a short distal segment.
AB  - PURPOSE: We assessed the long-term functional and urodynamic outcomes of a
      modified sigmoid neobladder. MATERIALS AND METHODS: A total of 50 patients
      received a sigmoid neobladder with a short distal segment after radical
      cystoprostatectomy. Patients were followed at 3-month intervals the first year
      and every 6 months thereafter. Continence and voiding patterns were assessed
      using questionnaires and interview. The International Continence Society
      classification was used after 1996. Urodynamic assessment was performed 3 times
      during followup. RESULTS: Mean sigmoid segment length +/- SD was 18 cm (+/- 2.8).
      Mean followup was 38 months (+/- 24.8). Ureter stricture and reflux were present
      in 8% and 17% of the reimplanted units, respectively. Mean creatinine serum
      levels did not change after surgery and remained stable during followup. At 2
      years 89% of the patients were continent in the daytime and 90% had good or
      satisfactory daytime continence according to the International Continence Society
      classification. At 3 years 77% of the patients voided every 3 or 4 hours during
      the day. Nighttime continence was poor. Only 10% of the patients complied with an
      alarm program. Mean maximal capacity of the reservoir was 300 ml and remained
      stable during followup. Mean intrareservoir pressure at maximal capacity
      decreased from 61 to 51 cm H2O from the first to the third urodynamic evaluation.
      No patient required clean intermittent catheterization. CONCLUSIONS: This
      modified sigmoid neobladder offers good daytime continence with low post-void
      residual and adequate daytime micturition frequency. Nighttime continence is
      poor. The presence of high intrareservoir pressures did not impair renal
      function.

PMID- 16094010
TI  - Consensus statement on urethral trauma.

PMID- 16094011
TI  - Factor VIIa for correction of traumatic coagulopathy.

PMID- 16094012
TI  - Ectopic placement of AMS 800 urinary control system pressure-regulating balloon.

PMID- 16094013
TI  - Reconstructing penile supersonic transporter (SST) deformity using glanulopexy
      (glans fixation).

PMID- 16094014
TI  - Neobladder-vaginal fistula after cystectomy and orthotopic neobladder
      construction.

PMID- 16094015
TI  - A three-centre experience of orthotopic neobladder reconstruction after radical
      cystectomy: initial results.

PMID- 16094016
TI  - Urethral recurrence after cystoprostatectomy: implications for urinary diversion
      and monitoring.

PMID- 16094017
TI  - Using the circumstances of symptom experience to assess the severity of urgency
      in the overactive bladder.
AB  - PURPOSE: We identified a method for quantifying the symptoms of the overactive
      bladder that addresses the assessment of urgency. MATERIALS AND METHODS: An
      observational study of a cohort was used. Data were collected prospectively from
      5,423 consultations on 1,797 patients (158 males and 1,639 females) being
      assessed and treated for the overactive bladder. The study was conducted during 5
      years. The reported frequencies and incontinence episodes were recorded. Using
      ranked ordinal scales (none, mild, moderate, severe) the symptoms of urgency and
      urge incontinence associated with waking and rising, hearing running water,
      arriving home ("latchkey"), cold weather and when feeling tired or worried were
      noted. The experiences of urgency and urge incontinence, without reference to the
      circumstances in which they were experienced were similarly assessed and if on
      treatment, they were asked to grade their overall response. RESULTS: Reported
      urinary frequency and incontinence episodes were strongly associated with patient
      grading of response to treatment. Therefore, the symptoms assessed on the scale
      of none, mild, moderate and severe were compared with disease severity by using
      reported frequency and incontinence episodes. The description of the symptoms
      with reference to the situations in which they were experienced showed clear
      associations with frequency and incontinence, falling along a progressive scale.
      An overall pattern could be detected in that at points on the scale of none,
      mild, moderate and severe, the least frequency and incontinence tended to be
      associated with waking, rising and latchkey symptoms. Next followed symptoms
      precipitated by running water and cold weather. Aggravation by fatigue or worry
      was associated with the greatest disease severity (ANOVA F = 8.9, p <0.001). This
      scale covered a wide range from frequencies of 7 to 15 times daily and
      incontinence episodes through 0 to 4 times daily. CONCLUSIONS: Qualifying the
      experience of urgency and urge incontinence, according to the circumstances in
      which these symptoms are experienced, seems to offer a promising new method for
      assessing the severity of urgency and urge incontinence.

PMID- 16094018
TI  - Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers
      following intradetrusor injections of botulinum toxin for human detrusor
      overactivity.
AB  - PURPOSE: Botulinum neurotoxin type A (BoNT/A) is effective in the treatment of
      intractable detrusor overactivity (DO). In addition to its known inhibitory
      effect on presynaptic release of acetylcholine by motor terminals, there is
      increasing evidence that BoNT/A may affect sensory fibers. We investigated a
      possible effect of BoNT/A on human bladder afferent mechanisms by studying the
      sensory receptors P2X3 and TRPV1 in biopsies from patients with neurogenic or
      idiopathic DO. MATERIALS AND METHODS: A total of 38 patients (22 with neurogenic
      DO, 16 with idiopathic DO) with intractable DO were treated with intradetrusor
      BoNT/A, and bladder biopsies were taken at 4 and 16 weeks. Urodynamics and
      voiding diary were also recorded. Specimens were studied immunohistochemically
      for P2X3, TRPV1 and the pan-neuronal marker PGP9.5, in comparison with controls.
      RESULTS: P2X3-immunoreactive and TRPV1-immunoreactive (-IR) fibers were decreased
      at 4 weeks after BoNT/A, and more significantly at 16 weeks (paired t test
      p=0.0004 and p=0.0008, respectively), when significant improvements were observed
      in clinical and urodynamic parameters. P2X3-IR fiber decrease was significantly
      correlated with reduction of urgency episodes at 4 and 16 weeks (p=0.0013 at 4
      weeks and p=0.02 at 16 weeks), but not maximum cystometric capacity or detrusor
      pressures. TRPV1-IR fiber decrease showed a similar trend. PGP9.5-IR
      suburothelial fibers remained unchanged after treatment at both followups (p=0.85
      and p=0.21 at 4 and 16 weeks, respectively). Urothelial cell P2X3-IR and TRPV1-IR
      also appeared unchanged. CONCLUSIONS: Decreased levels of sensory receptors P2X3
      and/or TRPV1 may contribute to the clinical effect of BoNT/A in detrusor
      overactivity.

PMID- 16094019
TI  - A comparison between the response of patients with idiopathic detrusor
      overactivity and neurogenic detrusor overactivity to the first intradetrusor
      injection of botulinum-A toxin.
AB  - PURPOSE: Several studies have shown that intradetrusor injections of botulinum
      neurotoxin type A (BoNT/A) may effectively treat intractable spinal neurogenic
      detrusor overactivity (NDO), but fewer reports exist on the use of BoNT/A in
      patients with idiopathic detrusor overactivity (IDO). The purpose of this study
      was to investigate whether comparable efficacy could be displayed in the response
      of patients with IDO to those with NDO. MATERIALS AND METHODS: In a prospective,
      open label study, patients with urgency, and/or urgency incontinence due to
      urodynamically proven intractable detrusor overactivity received 300 units (NDO)
      or 200 units (IDO) of Botox injected into the bladder with a minimally invasive
      outpatient technique. Urodynamic maximum cystometric capacity and maximum
      detrusor pressure during filling, frequency of voids (frequency), number of
      incontinence episodes (leak) and number of voids associated with urgency per 24
      hours (urgency) from 4-day voiding diaries were compared between the 2 groups at
      baseline and for changes at 4 and 16 weeks after treatment. RESULTS: A total of
      44 patients with spinal NDO and 31 with IDO were treated. At 16 weeks, mean +/-
      standard error maximum cystometric capacity increased from 229.1 +/- 24.8 to
      427.0 +/- 26.9 ml, p <0.0001 in NDO and from 193.6 +/- 24.0 to 327.1 +/- 36.1 ml,
      p=0.0008 in IDO. Maximum detrusor pressure during filling decreased from 60.7 +/-
      6.8 to 26.1 +/- 3.7 cm H2O, p <0.0001 in NDO and from 62.1 +/- 10.8 to 45.1 +/-
      8.1 cm H2O, p=0.027 in IDO. Frequency decreased from 12.3 +/- 0.7 to 6.6 +/- 0.6
      voids per 24 hours, p <0.0001 in NDO and from 13.6 +/- 1.1 to 8.3 +/- 0.7,
      p=0.0002 in IDO. Leak decreased from 3.9 +/- 0.5 to 0.7 +/- 0.2 incontinence
      episodes per 24 hours, p <0.0001 in NDO and from 3.2 +/- 0.8 to 0.6 +/- 0.3,
      p=0.0017 in IDO, and urgency decreased from 7.5 +/- 0.6 to 1.44 +/- 0.3 episodes
      per 24 hours, p <0.0001 in NDO and from 10.9 +/- 1.7 to 4.9 +/- 1.1, p <0.0001 in
      IDO. The 2 groups were comparable for baseline data, but percent improvement in
      urgency was greater in patients with NDO at 4 weeks (78.2% vs 56.3%, p=0.019) and
      16 weeks (78.3% vs 50.7%, p=0.013). Of patients with NDO 69% required self
      catheterization de novo posttreatment compared with 19.3% of those with IDO.
      CONCLUSIONS: Patients with intractable IDO respond to intradetrusor BoNT/A with
      equally significant improvements in urodynamic and lower urinary tract symptom
      parameters as those with spinal NDO, despite the lower dose of toxin used.

PMID- 16094020
TI  - Autologous fascial sling vs polypropylene tape at short-term followup: a
      prospective randomized study.
AB  - PURPOSE: The incidence of urinary incontinence in women of childbearing age is
      about 30%. Around half have stress incontinence. Many treatment modalities have
      been elucidated to treat stress incontinence, and among the most popular are
      rectus fascia sling and tension-free vaginal tape (TVT). The introduction of TVT
      to the urological armamentarium put a multiplicity of synthetic materials into
      use in the correction of stress urinary incontinence. A comparison of the impact
      of these 2 commonly used techniques is needed. MATERIALS AND METHODS: A total of
      53 female patients older than 21 years (mean age 45.09) were randomized, using
      closed envelopes, to undergo TVT or rectus fascia sling. Randomization was
      performed after patients received spinal anesthesia. One surgeon performed the 2
      types of treatment. Associated grade 2 cystocele was simultaneously corrected.
      Patients with bladder or urethral pathology, as well as those with cystocele
      greater than grade 2, were excluded from analysis. RESULTS: All 53 patients
      completed 6 months of followup and all had stress urinary incontinence. There
      were 15 patients who underwent sling surgery and 17 who underwent TVT who had
      concomitant grade 1 or 2 cystocele. No statistically significant difference was
      found between the 2 groups at baseline. Cure was accomplished in 23 of 25 (92%)
      with sling and in 26 of 28 (92.9%) with TVT at first followup visit (1 week).
      There were 7 patients who needed at least 1 extra week of catheterization in the
      sling group and 3 in the TVT group. No significant difference was detected in
      terms of post-void residual urine, symptom score, and filling and voiding
      parameters. At 6 months 1 patient had de novo detrusor overactivity and 7 had
      wound pain. Compared to those with TVT, 2 cases of sling were considered
      treatment failures, none had de novo overactivity and 2 had wound pain. None of
      the patients had symptoms suggestive of urethral erosion. CONCLUSIONS: Rectus
      fascia sling and TVT seem to be equally effective regarding primary outcome
      measure (ie cure of stress incontinence). Symptom score related to incontinence
      surgery as well as simultaneous correction of cystocele are comparable in the 2
      groups. Fascial sling is a longer treatment process yet it is more economical.
      Longer followup is vital before rigorous conclusions can be drawn.

PMID- 16094021
TI  - Transurethral collagen injections for male intrinsic sphincter deficiency: the
      University of Texas-Houston experience.
AB  - PURPOSE: Injectable agents are used to increase urethral coaptation for the
      treatment of intrinsic sphincter deficiency. We evaluated the long-term results
      and complications of transurethral collagen injections in males. MATERIALS AND
      METHODS: We reviewed the charts of 322 men (mean age 67.2 years, range 40 to 91)
      with intrinsic sphincter deficiency after therapy for prostate carcinoma (307) or
      benign prostatic hyperplasia (15) who received transurethral collagen injections.
      The analysis included types and combinations of treatment for prostate cancer or
      benign prostatic hyperplasia, pre-procedure voiding symptoms, total collagen
      received, maximal percentage improvement and durability of effect. RESULTS: The
      mean length of followup was 40.1 (+/-13.2) months. Overall, the mean number of
      injections was 4.37 (+/-2.09). Mean percent improvement after a series of
      injections was 44.59 (+/-38.26). Mean pad use before and after injection was
      statistically different (5.15 vs 2.98, p=0.0001). Mean duration of response was
      6.3 (+/-8.14) months. In those who achieved complete continence (17%), the mean
      duration of response was 11.1 (+/-8.87) months. Within this group the mean number
      of injections and ml of collagen injected were 3.83 and 29.27, respectively. Five
      patients (1.5%) complained of a quantitative increase in leakage after their
      series of collagen injections. CONCLUSIONS: Transurethral collagen injections are
      a good option for short-term therapy in men with post-prostatectomy incontinence.
      The mean number of injections to achieve a plateau is 3 to 4, regardless of
      initial severity of incontinence. Those in the radical prostatectomy only
      treatment group are statistically more likely to achieve continence than all
      other treatment groups.

PMID- 16094023
TI  - Seeking evidence that cell kill guided thermotherapy gives results not inferior
      to those of transurethral prostate resection: results of a pooled analysis of 3
      studies of feedback transurethral microwave thermotherapy.
AB  - PURPOSE: We compared ProstaLund Feedback Treatment (PLFT) to transurethral
      prostate resection (TURP) in terms of efficacy and safety in a pooled analysis of
      3 clinical studies with 1-year followup. MATERIALS AND METHODS: Overall raw data
      on 183 patients with PLFT and 65 with TURP were pooled. All studies had identical
      inclusion criteria, and the efficacy and safety of the method were evaluated
      using the International Prostate Symptom Score, maximum urine flow (Qmax),
      responder rate, bother score, prostate volume reduction and adverse events.
      RESULTS: The response rate was 85.3% and 85.9% in the PLFT and TURP groups,
      respectively. One-sided 95% CI analysis showed the noninferiority of PLFT vs TURP
      for this variable. Mean International Prostate Symptom Score was significantly
      decreased in the PLFT and TURP groups after 12 months (from 20.9 to 6.4 and 20.7
      to 7.1, respectively). The 1-sided upper 95% CI of PLFT was within the
      noninferiority definition compared with that of TURP. The bother score decrease
      in the PLFT and TURP groups was not significant different (70.9% and 64.0%,
      respectively). An increase in Qmax from 7.7 to 16.1 ml per second 12 months after
      PLFT was noted, while the improvement in Qmax in the TURP group was higher (from
      7.5 to 18.6 ml per second). The 1-sided lower 95% CI was close (0.76) but it did
      not attain the predetermined level of noninferiority (0.80). Mean transurethral
      ultrasound determined volume 12 months after PLFT and TURP was reduced by 32.8%
      and 58.1%, respectively. A significant correlation between the transurethral
      ultrasound determined prostate volume reduction and estimated cell kill was found
      (r = 0.456, p <0.000001). Serious adverse events with causality occurred in 15.4%
      of patients with TURP compared with 6.0% in those with PLFT (p = 0.035).
      CONCLUSIONS: Combined experience from our pooled analysis indicates that PLFT
      challenges TURP in terms of efficacy and safety after 1 year of followup.

PMID- 16094022
TI  - Holmium laser enucleation of the prostate for men with urinary retention.
AB  - PURPOSE: Holmium laser enucleation of the prostate (HoLEP) is an established
      procedure for the treatment of patients with benign prostatic hyperplasia. We
      performed a study to examine a group of patients in urinary retention treated by
      HoLEP. MATERIALS AND METHODS: A retrospective analysis of 164 consecutive
      patients with urinary retention who underwent HoLEP between January 2000 and
      August 2004 was performed. RESULTS: Mean patient age was 72.1 years (range 34 to
      95). Mean duration of urinary retention was 28.9 days (range 2 to 365). Mean
      preoperative transrectal ultrasound measured prostate volume was 107.1 cc (range
      5 to 242). Mean weight of resected tissue was 81.9 grams (range 2.5 to 271). Mean
      duration of postoperative catheterization and hospitalization was 22.5 hours
      (range 2 to 240) and 33.7 hours (range 2 to 144), respectively. All patients were
      able to void following treatment and remain catheter free. CONCLUSIONS: HoLEP is
      an effective treatment, with low morbidity, for patients with urinary retention.
      These results suggest that HoLEP may be the ideal treatment for men with urinary
      retention due to benign prostatic obstruction.

PMID- 16094024
TI  - Transvaginal electrical stimulation in the treatment of urinary incontinence.

PMID- 16094025
TI  - Long-term results of sacral neuromodulation for women with urinary retention.

PMID- 16094026
TI  - Posterior tibial nerve stimulation in the treatment of voiding dysfunction:
      urodynamic data.

PMID- 16094027
TI  - Tension-free vaginal tape: do patients who fail to follow-up have the same
      results as those who do?

PMID- 16094028
TI  - Transvaginal surgery in the octogenarian using cadaveric fascia for pelvic
      prolapse and stress incontinence: minimal one-year results compared to younger
      patients.

PMID- 16094029
TI  - Correlation between lower urinary tract symptoms and urethral function in benign
      prostatic hyperplasia.

PMID- 16094030
TI  - The effects of the tension-free vaginal tape on voiding function: a prospective
      evaluation.

PMID- 16094031
TI  - Single-blind, randomized controlled study of the clinical and urodynamic effects
      of an alpha-blocker (naftopidil) and phytotherapy (eviprostat) in the treatment
      of benign prostatic hyperplasia.

PMID- 16094032
TI  - Induction and function of CYR61 (CCN1) in prostatic stromal and epithelial cells:
      CYR61 is required for prostatic cell proliferation.

PMID- 16094033
TI  - Ventilatory and hemodynamic changes during retroperitoneal and transperitoneal
      laparoscopic nephrectomy: a prospective real-time comparison.
AB  - PURPOSE: Nephrectomies are currently performed via the transperitoneal or
      retroperitoneal laparoscopic approach. We compared the ventilatory and
      hemodynamic effects of these approaches. MATERIALS AND METHODS: After
      institutional ethics committee approval was obtained patients requiring
      nephrectomy in a 9-month period were prospectively allocated to the
      retroperitoneal (24) or transperitoneal (15) approach. All were initially
      ventilated in the volume controlled mode (10 ml kg tidal volume). Intraoperative
      fingertip, pulse derived arterial oxygen saturation less than 97%, end tidal CO2
      partial pressure greater than 40 mm Hg and peak inspiratory pressure greater than
      36 cm H2O necessitated changes in ventilatory parameters, as deemed necessary by
      the anesthetist. If tidal volume decreased greater than 25% of baseline, pressure
      controlled ventilation was begun instead. RESULTS: Peak inspiratory and plateau
      pressures increased for the transperitoneal approach by approximately 30% more
      than in the retroperitoneal group (p <0.05). Volume controlled ventilation was
      changed to pressure controlled ventilation in 8 transperitoneal vs zero
      retroperitoneal cases (p <0.05). Heart rate, and systolic and diastolic blood
      pressure increased by approximately 13% more in the transperitoneal than in the
      retroperitoneal group (p <0.05). CONCLUSIONS: Nephrectomy via the retroperitoneal
      laparoscopic approach interferes with ventilatory and hemodynamic functions less
      than nephrectomy via the transperitoneal approach.

PMID- 16094034
TI  - Obesity in living kidney donors: clinical characteristics and outcomes in the era
      of laparoscopic donor nephrectomy.

PMID- 16094035
TI  - Retroperitoneoscopic live donor nephrectomy (RPLDN): establishment and initial
      experience of RPLDN at a single center.

PMID- 16094036
TI  - Laparoscopic renal-adrenal surgery in patients on oral anticoagulant therapy.
AB  - PURPOSE: Patients requiring chronic anticoagulation are theoretically at
      increased risk for hemorrhage or thromboembolism perioperatively. Experience with
      laparoscopic renal/adrenal surgery in patients on chronic warfarin is limited. We
      assessed hemorrhagic/thromboembolic complications in this group of patients.
      MATERIALS AND METHODS: The records of 787 patients undergoing laparoscopic
      renal/adrenal surgery were retrospectively reviewed. A total of 25 patients on
      chronic oral anticoagulation with warfarin were identified. The indications for
      warfarin therapy as well as perioperative management were reviewed. Clinical
      parameters, including operative time, estimated blood loss,
      hemorrhagic/thromboembolic complications and transfusions, were documented and
      compared with those in patients not receiving chronic anticoagulation. RESULTS:
      Atrial fibrillation (56% of cases) and a prosthetic mitral valve (28%) were the
      most frequent indications for chronic anticoagulation. Bridging anticoagulation
      with unfractionated heparin was the most frequent management method (68% of
      cases). Patients with anticoagulation were older (p <0.001) and hospitalized
      longer (<0.001) than those without anticoagulation. Operative time, estimated
      blood loss and the conversion rate were not significantly different between the
      groups. However patients on chronic warfarin significantly more often required
      transfusion (24% vs 5.2%, p <0.005) and had more postoperative bleeding episodes
      (8% vs 0.9%, p <0.05) than patients not on chronic anticoagulation. No
      thromboembolic events occurred in the anticoagulated group, while 3 occurred in
      the nonanticoagulated group (p = 1). CONCLUSIONS: Laparoscopic renal/adrenal
      surgery in patients requiring chronic anticoagulation therapy can be performed
      safely. The risk of intraoperative bleeding is not increased, although the
      incidence of postoperative bleeding as well as transfusions is higher.

PMID- 16094037
TI  - Early detection of acute renal failure by serum cystatin C.

PMID- 16094038
TI  - Reversible acute renal failure after unilateral extracorporeal shock-wave
      lithotripsy.

PMID- 16094039
TI  - Corticosteroids for treating severe sepsis and septic shock.

PMID- 16094040
TI  - Peyronie's disease in diabetic patients being screened for erectile dysfunction.
AB  - PURPOSE: We assessed the prevalence of Peyronie's disease (PD) in type 2 diabetic
      patients who were screened for erectile dysfunction (ED). MATERIALS AND METHODS:
      A total of 1,133 male diabetic Saudi patients were enrolled in this study.
      Patients were screened for ED using the International Index for Erectile
      Function. At the screening time, all patients were also interviewed for
      sociodemographic data and risk factors for ED and diabetes that included age,
      obesity, smoking, hypertension, dyslipidemia, ischemic heart disease and
      psychological disorders. Medical history included diabetes, duration of diabetes
      and diabetes related complications. The diagnosis of Peyronie's disease was based
      on a palpable penile plaque or acquired penile curvature. RESULTS: Mean age +/-
      SD for the study sample was 53.9 +/- 10.8 years. Of the patients, 8.1% were
      diagnosed as having PD. Penile plaque and curvature were the most common
      findings. About 75% of the patients had long duration and progressive course of
      their complaint. Significant associations between PD and both ED and longer
      duration ED were detected. There were also significant associations between PD
      and age, obesity, smoking, duration and number of cigarettes smoked per day.
      Dyslipidemia, psychological disorders and presence of at least 1 risk factor were
      significantly associated with PD. There were significant associations between
      longer duration and poor metabolic control of diabetes and PD. CONCLUSIONS:
      Peyronie's disease was prevalent among diabetic patients being screened for ED.
      The study offered a quantitative estimate of the prevalence of PD, and
      investigated the association of main risk factors and comorbidities of diabetes
      and ED with PD.

PMID- 16094041
TI  - Boys with posterior urethral valves: outcome concerning renal function, bladder
      function and paternity at ages 31 to 44 years.
AB  - PURPOSE: The short-term prognosis for boys with posterior urethral valves (PUV)
      has improved in recent decades, but the long-term prognosis in terms of renal and
      bladder function and fertility is still a matter of great concern. This study is
      a followup of boys with PUV and dilated upper urinary tract treated in 1956 to
      1970 at the Children's Hospital in Goteborg, Sweden. MATERIALS AND METHODS: The
      records of 54 boys treated for PUV were reviewed. Of 27 boys with PUV and upper
      urinary tract dilation, 5 boys (18%) died at an early age and 3 boys were lost to
      followup during adolescence, leaving 19 to be included in the followup. They all
      answered a questionnaire about renal and bladder function and paternity. RESULTS:
      Of the 19 men 32% were uremic, 21% had moderate renal failure and 47% had not
      been checked since adolescence. There were signs of bladder dysfunction in 40%
      and all these subjects had bladder symptoms suggesting detrusor weakness as the
      cause. All the men were continent. The ability to father children was dependent
      on whether or not the man was uremic. CONCLUSIONS: This long-term followup study
      emphasizes the importance of checking renal and bladder function throughout life
      in men born with PUV. Increasing attention to bladder dysfunction and its early
      treatment could probably improve the long-term prognosis.

PMID- 16094042
TI  - Prognostic parameters in adult impalpable ultrasonographic lesions of the
      testicle.
AB  - PURPOSE: Through an analysis of individual published data we assessed whether
      prognostic criteria exist for adult impalpable testicular sonographic lesions.
      MATERIALS AND METHODS: We performed a bibliographic search on PubMed, MEDLINE,
      EMBASE online databases from 1990 to May 2004 using search words such as
      sonographic lesions of the testicle, impalpable tumors of the testicle and
      impalpable testicular lesions. Six articles were found that presented a
      description of the histological characteristics, patient age, lesion dimensions,
      presence of cryptorchidism and association with tumors in other parts of the
      body. A multivariate analysis was performed comparing the characteristics that
      appeared more interesting from a univariate analysis. RESULTS: The
      characteristics of the 48 impalpable sonographic lesions were examined.
      Histologically 15 of the lesions were Leydig cell tumors (31%), 12 (25%)
      seminomas, 7 (14.5%) nonseminomatous germ cell tumors, 2 (4.5%) Sertoli cell
      tumors, 12 (25%) benign forms (fibrosis, infarct, lipoma, mesothelial
      hyperplasia, adenomatoid tumor). The average age was 37.5, average dimension was
      10.11 mm. The lesions were hypoechoic in 85% of the cases. Of the patients 31%
      were infertile. Multivariate analysis showed that histological data were
      correlated with lesion dimensions and presence of infertility. Dimension was
      particularly related to germ cell tumors (for dimensions between 16 and 32 mm
      relative risk ratio [RRR] = 13.97, p=0.0449). Infertility proved significant in
      defining stromal tumors (RRR = 9,681, p=0.022) CONCLUSIONS: Although with the
      limits of a retrospective study consisting in an analysis of individual data,
      interesting correlations between malignant pathologies and the initial
      characteristics of impalpable sonographic lesions were revealed. In particular an
      interesting correlation was found between the dimensions of the lesion and the
      malignant pathology and between Leydig cell tumor and infertility.

PMID- 16094043
TI  - A clinical entity of cystic dilatation of the utricle associated with
      hemospermia.
AB  - PURPOSE: We investigated the mechanism of hemospermia in patients with a midline
      cyst (MLC) of the prostate, focusing on cystic dilatation of the utricle (CDU) as
      a possible causative lesion. MATERIALS AND METHODS: Of 138 patients with
      hemospermia 30 (22%) had an MLC, of whom 19 underwent transperineal needle
      aspiration of the MLC and bilateral seminal vesicles to determine the site of
      bleeding. Following MLC aspiration a mixture of dye and contrast medium was
      injected. The verumontanum was observed endoscopically and pelvic x-ray was done.
      RESULTS: Seminal vesicle fluid on 1 or 2 sides was hemorrhagic in 13 of the 19
      patients (aspiration failed in 6) and fluid from the MLC was nonhemorrhagic in 5
      of the 19 (aspiration failed in 7). The MLC communicated with the urethra (CDU)
      in 15 patients (79%) and with 1 or 2 ejaculatory ducts in 11 (58%). In 5 of 11
      patients with communication with the ejaculatory duct hemospermia persisted for
      more than 1 year. Four of these patients were cured by transurethral unroofing of
      the CDU. CONCLUSIONS: CDU is a significant underlying lesion for hemospermia.
      Communication with the ejaculatory ducts was frequent in patients with chronic
      hemospermia and transurethral unroofing was effective for eliminating
      hemospermia.

PMID- 16094044
TI  - Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology.

PMID- 16094045
TI  - Expression and functional activity of phosphodiesterase type 5 in human and
      rabbit vas deferens.

PMID- 16094046
TI  - Cavernosal dysfunction in a rabbit model of hyperhomocysteinaemia.

PMID- 16094047
TI  - 3',5'-Cyclic nucleotide phosphodiesterase 11A: localization in human tissues.

PMID- 16094048
TI  - Testosterone selectively reduces the high molecular weight form of adiponectin by
      inhibiting its secretion from adipocytes.

PMID- 16094049
TI  - The effect of neural embryonic stem cell therapy in a rat model of cavernosal
      nerve injury.

PMID- 16094050
TI  - Genetic abnormalities among severely oligospermic men who are candidates for
      intracytoplasmic sperm injection.

PMID- 16094051
TI  - Absence of de novo Y-chromosome microdeletions in male children conceived through
      intracytoplasmic sperm injection.

PMID- 16094052
TI  - Psychological follow-up study of 5-year-old ICSI children.

PMID- 16094053
TI  - Comparison of the outcome of intracytoplasmic sperm injection in obstructive and
      non-obstructive azoospermia in the first cycle: a report of case series and meta
      analysis.

PMID- 16094054
TI  - Efficient treatment of infertility due to sperm DNA damage by ICSI with
      testicular spermatozoa.

PMID- 16094055
TI  - Transurethral resection of the ejaculatory ducts for treating ejaculatory
      symptoms.

PMID- 16094056
TI  - Quality of care: partial cystectomy for bladder cancer--a case of inappropriate
      use?
AB  - PURPOSE: Partial cystectomy is perceived to be a less morbid, less technically
      demanding procedure than radical cystectomy, although only select patients
      (approximately 6% to 10%) are appropriate candidates (solitary tumor in
      space/time, absence of carcinoma in situ). From a quality of care perspective,
      overuse of partial cystectomy may signify inappropriate delivery of health care.
      MATERIALS AND METHODS: Subjects who underwent extirpative treatment for bladder
      cancer between 1988 and 2000 were identified within the Surveillance,
      Epidemiology and End Results (SEER, 3,381) registry and the Nationwide Inpatient
      Sample (NIS, 22,088). Adjusted models were developed to identify clinical factors
      independently associated with the use of partial cystectomy for bladder cancer
      treatment within each sample. RESULTS: Among patients who underwent extirpative
      surgery for bladder cancer, 18% and 20% of those in SEER and NIS, respectively,
      underwent partial cystectomy. Significant decreases in use between early and
      later years were noted in both samples (SEER-22% to 13%, NIS-24% to 17%, both p
      <0.0001). Partial cystectomy was preferentially used in the elderly, those with
      stage I disease, females and black patients. Furthermore, partial cystectomy was
      more commonly provided in rural, nonteaching, low volume hospitals. CONCLUSIONS:
      Trends in national use of partial cystectomy are consistent between the NIS and
      SEER with 13% to 17% of patients currently being treated with partial in lieu of
      radical cystectomy. Partial cystectomy is disproportionately used in certain
      medical centers (nonteaching, rural, low volume) and patient populations
      (elderly, black, females, stage I disease) reflecting selective referral or
      overuse.

PMID- 16094057
TI  - Changes in disease specific and generic quality of life related to changes in
      lower urinary tract symptoms: the Krimpen study.
AB  - PURPOSE: We determined if and to what extent longitudinal changes in lower
      urinary tract symptoms are related to disease specific and generic quality of
      life in men. MATERIAL AND METHODS: A longitudinal, population based study with a
      followup of 4.2 years was done in 1,688 who were 50 to 79 years old. Data were
      collected through self-administered questionnaires, including the Sickness Impact
      Profile (3 domains), Inventory of Subjective Health, International Prostate
      Symptom Score (I-PSS) and Benign Prostatic Hyperplasia Impact Index. Moreover,
      they completed various physical and urological measurements. Mean I-PSS and
      quality of life scores at baseline and followup were analyzed for certain
      subgroups. Multiple linear regression was used to determine the change in quality
      of life in relation to baseline I-PSS, I-PSS changes between baseline and
      followup, and age. RESULTS: Although mean I-PSS increased with time, the average
      generic quality of life improved and almost a third of the men reported better
      disease specific quality of life. Multiple linear regression revealed that
      disease specific quality of life was associated with I-PSS at baseline, changes
      in I-PSS between baseline and followup, and age. However, generic quality of life
      scores were not associated with these parameters. CONCLUSIONS: Changes in lower
      urinary tract symptoms severity had little impact on disease specific quality of
      life in 50 to 79-year-old men or on generic quality of life during the 4.2-year
      followup.

PMID- 16094058
TI  - Health related quality of life and direct medical care cost in newly diagnosed
      younger men with prostate cancer.
AB  - PURPOSE: We evaluated health related quality of life (HRQOL) and the direct
      medical care cost (DMC) in young men receiving radical prostatectomy. MATERIALS
      AND METHODS: In this prospective cohort study, 40 newly diagnosed patients with
      prostate cancer (PCa) who were younger than 65 years were matched with 40 cancer
      free men. Participants completed the Medical Outcome Study Short Form and UCLA
      PCa Index surveys prior to treatment, and at 3, 6, 12 and 24-month followup. Cost
      data were obtained from a hospital based administrative database and clinical
      data were obtained via structured medical chart review. Demographics and HRQOL
      were compared using the t, Fisher exact and chi-square tests. The Wilcoxon and
      log-T tests were used to compare DMC. Multivariate regression models were used to
      assess the incremental cost of PCa and predictors of 24-month prostate specific
      HRQOL. RESULTS: Patients with PCa had a mean annual DMC of 4,160 dollars for the
      treatment year with a mean length of stay of 3.5 days. They had 3-fold higher DMC
      than controls. At 12 months, generic HRQOL values were similar to baseline
      values. Sexual function showed trends toward improvement 6 months after surgery.
      Urinary function improved significantly by 6 months, although it decreased
      thereafter. Bowel function and bother returned to baseline values by 3 months. On
      multivariate regression marital status was a significant predictor of 5 domains
      of prostate specific HRQOL at 24 months. CONCLUSIONS: Patients with PCa reported
      weaker sexual function, urinary function and sexual bother at 2 years after
      treatment compared with their baseline values. There exists an opportunity for
      improving prostate specific HRQOL in men with early stage PCa.

PMID- 16094059
TI  - Intensive lifestyle changes may affect the progression of prostate cancer.
AB  - PURPOSE: Men with prostate cancer are often advised to make changes in diet and
      lifestyle, although the impact of these changes has not been well documented.
      Therefore, we evaluated the effects of comprehensive lifestyle changes on
      prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell
      growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS
      AND METHODS: Patient recruitment was limited to men who had chosen not to undergo
      any conventional treatment, which provided an unusual opportunity to have a
      nonintervention randomized control group to avoid the confounding effects of
      interventions such as radiation, surgery or androgen deprivation therapy. A total
      of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than
      7 were randomly assigned to an experimental group that was asked to make
      comprehensive lifestyle changes or to a usual care control group. RESULTS: None
      of the experimental group patients but 6 control patients underwent conventional
      treatment due to an increase in PSA and/or progression of disease on magnetic
      resonance imaging. PSA decreased 4% in the experimental group but increased 6% in
      the control group (p = 0.016). The growth of LNCaP prostate cancer cells
      (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8
      times more by serum from the experimental than from the control group (70% vs 9%,
      p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly
      associated with the degree of change in diet and lifestyle. CONCLUSIONS:
      Intensive lifestyle changes may affect the progression of early, low grade
      prostate cancer in men. Further studies and longer term followup are warranted.

PMID- 16094060
TI  - Pediatric ureteroscopic stone management.
AB  - PURPOSE: We reviewed our experience of 5 years using ureteroscopy with laser
      lithotripsy to treat stone disease in prepubertal children. MATERIALS AND
      METHODS: A retrospective review was performed of all ureteroscopic procedures
      performed in prepubertal children. RESULTS: A total of 33 ureteroscopic
      procedures were performed in 29 prepubertal children (15 males and 14 females) 5
      to 144 months old (mean age 94 months, including 3 patients 24 months or
      younger). Stones were located in the renal pelvis in 1 case (3%), proximal ureter
      in 3 (9%), mid ureter in 5 (15%) and distal ureter in 24 (73%). Stone size ranged
      from 3 to 14 mm (mean 6). Eight patients required balloon dilation of the
      ureteral orifice. Followup ranged from 1 to 66 months (mean 11). Stone-free rate
      after initial ureteroscopy and laser lithotripsy was 88%, with all distal and mid
      ureteral stones (3 to 9 mm, mean 5) successfully treated. Three patients with
      proximal ureteral stones 7 to 14 mm in diameter (mean 10.3) required a secondary
      procedure (repeat ureteroscopy in 2 and shock wave lithotripsy in 1) to become
      stone-free. One patient with cystinuria and a renal pelvic stone measuring 14 mm
      required shock wave lithotripsy and percutaneous nephrostolithotomy. There were
      no major complications of ureteroscopy but there was 1 case of extravasation at
      the ureterovesical junction after balloon dilation that was managed with stent
      placement. CONCLUSIONS: Although more patients and longer followup are needed,
      ureteroscopy with laser lithotripsy is an excellent first line treatment for
      children with stones in whom conservative therapy fails, especially those with
      distal and mid ureteral stones. Patients with a stone burden of 10 mm or greater,
      especially in the proximal ureter, likely will require a secondary procedure to
      become stone-free.

PMID- 16094061
TI  - Long-term patient reported outcome and satisfaction after oral mucosa graft
      urethroplasty for hypospadias.
AB  - PURPOSE: There is a paucity of long-term patient reported outcome data on surgery
      for hypospadias. We sought to evaluate genitourinary function and satisfaction
      after oral mucosa graft urethroplasty (OMGU) for hypospadias. MATERIALS AND
      METHODS: We identified 65 patients who had undergone OMGU at our institution
      between 1992 and 2003, and surveyed these patients to evaluate oral health,
      urinary function and satisfaction with outcomes. RESULTS: We located 51 patients
      who had undergone OMGU, of whom 43 (84%) agreed to participate in the study.
      Median followup was 6.9 years. Mean study age was 15.1 years. Of the patients 47%
      had severe hypospadias with failed previous repair and 42% had severe hypospadias
      with previous first stage surgery. Oral complaints were rare and primarily
      cosmetic. No patient whose oral harvest was limited to the cheek (vs lip) had
      cosmetic complaints. Urinary spray and stream deviation were reported by 11
      patients (26%) and 12 patients (28%), respectively. American Urological
      Association symptom scores were generally low (mean 5.6 +/- 6.0, range 0 to 21)
      but 7 patients (16%) had moderate symptoms and 2 (5%) had severe symptoms. Of the
      patients 60% were mostly satisfied or better with urinary function. Although
      satisfaction with penile appearance varied (51% of patients were satisfied), most
      patients (84%) were satisfied with the overall hypospadias care. Urinary symptom
      scores were significantly worse among patients who had post-OMGU complications (p
      = 0.004). Of these patients 38% had moderate or severe urinary symptoms, while
      95% of patients without complications had mild symptoms (p = 0.01). CONCLUSIONS:
      Many patients report good long-term outcomes of OMGU, although a subset of
      patients has significant urinary and cosmetic complaints that are more prevalent
      in association with surgical complications.

PMID- 16094062
TI  - Passive dilation by ureteral stenting before ureteroscopy: eliminating the need
      for active dilation.
AB  - PURPOSE: We sought to evaluate the use of passive dilation by stenting of
      ureteral orifices that were inaccessible at initial cystoscopic evaluation in
      children before a ureteroscopic procedure. MATERIALS AND METHODS: We evaluated
      all patients younger than 18 years undergoing a ureteroscopic procedure in whom
      the ureteral orifice could not be accessed endoscopically by a ureteroscope.
      RESULTS: A total of 26 children (14 boys and 12 girls) 7.3 to 14.1 years old
      (median age 10.3 years) underwent 28 passive dilations of initially inaccessible
      ureters. Stents remained indwelling for 2 to 8 weeks (median 3). All patients
      underwent successful ureteroscopy with a semirigid and/or flexible ureteroscope
      after preoperative stent placement. No patient required active dilation of the
      ureteral orifice at ureteroscopy. There were no complications from stent
      placement before the ureteroscopic procedures. No patient had a urinary tract
      infection or bladder spasms requiring anticholinergic therapy from stent
      insertion and/or early stent removal. CONCLUSIONS: Our study shows that passive
      dilation of the ureteral orifice in preparation for ureteroscopy is a
      straightforward, successful and beneficial technique in children, with no
      associated complications.

PMID- 16094063
TI  - Clonidine increases duration of bupivacaine caudal analgesia for
      ureteroneocystostomy: a double-blind prospective trial.
AB  - PURPOSE: We evaluated whether clonidine, when added to bupivacaine, would
      significantly prolong caudal analgesia and decrease opioid requirements in
      children undergoing ureteroneocystostomy. MATERIALS AND METHODS: A total of 35
      children 1 to 10 years old undergoing ureteroneocystostomy received a
      standardized regimen of general anesthesia, and were randomized to receive a
      preincision caudal block consisting of either 1 ml/kg 0.125% bupivacaine
      (controls) or 1 ml/kg 0.125% bupivacaine with 1 microg/kg clonidine (treatment
      group). Caudal solutions also contained 1:400,000 epinephrine. Following the
      surgical procedure a second caudal block was performed with half of the original
      dose of medications. Caregivers were blinded to which caudal solution was
      administered. Postoperative outcome measures included pain scores, morphine
      requirements, duration of caudal analgesia and sedation scores. Statistical
      analysis was performed using ANOVA. RESULTS: The 2 study groups were similar for
      mean age, weight and length of surgical procedure. Two patients in the control
      group were excluded because of protocol violation. Intravenous morphine
      requirements for rescue therapy were 0.02 mg/kg in the postanesthesia care unit
      and 0.1 mg/kg on postoperative day 1 for the treatment group, compared to 0.05
      mg/kg and 0.2 mg/kg, respectively, for controls (p <0.05). Mean interval from
      anesthesia finish time to first administered dose of morphine was 8.0 hours for
      the treatment group and 3.9 hours for controls (p = 0.01). Five of 18 patients in
      the clonidine-bupivacaine group received no postoperative morphine, compared to 1
      of 15 in the bupivacaine group. No patient had development of hemodynamic
      instability, respiratory depression or sedation requiring treatment. CONCLUSIONS:
      The addition of clonidine to bupivacaine significantly increases the duration of
      caudal analgesia and decreases postoperative morphine requirements in children
      undergoing ureteroneocystostomy.

PMID- 16094064
TI  - Comparison of effects of treatment of primary nocturnal enuresis with oxybutynin
      plus desmopressin, desmopressin alone or imipramine alone: a randomized
      controlled clinical trial.
AB  - PURPOSE: We prospectively evaluated the efficacy of a combination of desmopressin
      and oxybutynin for treating children with nocturnal enuresis, compared to the
      single drugs imipramine and desmopressin. MATERIALS AND METHODS: We enrolled 158
      patients from 2003 to 2004. Children were randomly assigned to 1 of 3 groups and
      treated with desmopressin, imipramine or a combination of desmopressin plus
      oxybutynin. Of these patients 145 (100 boys and 45 girls, mean age 7.8 +/- 2.5
      years, range 5 to 15) were followed for more than 6 months. Efficacy was measured
      at 1, 3 and 6 months in terms of average enuretic frequency, 5-scale response
      based on change in nocturnal enuretic frequency after treatment and posttreatment
      enuretic frequency as a percentage of pretreatment baseline frequency. The latter
      efficacy was classified according to daytime voiding symptoms. Statistical
      evaluation was performed using chi-square tests and ANOVA. RESULTS: Of the 145
      children followed 48 received combination therapy, 49 received desmopressin and
      48 received imipramine. A total of 68 patients (47%) had monosymptomatic enuresis
      and 77 (53%) had polysymptomatic enuresis. Combination therapy produced the best
      and most rapid results regardless of whether the children had monosymptomatic or
      polysymptomatic enuresis. CONCLUSIONS: Combination therapy with desmopressin plus
      oxybutynin for the treatment of pediatric nocturnal enuresis was well tolerated,
      and gave significantly faster and more cost-effective results than single drug
      therapy using either desmopressin or imipramine.

PMID- 16094065
TI  - Renal pelvis cuff pyeloplasty for ureteropelvic junction obstruction for the high
      inserting ureter: an initial experience.
AB  - PURPOSE: Ureteropelvic junction (UPJ) obstruction can result from a high
      inserting ureter without intrinsic ureteral obstruction. We describe our initial
      experience using a renal pelvis cuff pyeloplasty technique to treat this cause of
      UPJ obstruction. MATERIALS AND METHODS: We reviewed our experience regarding all
      children who underwent renal pelvis cuff pyeloplasty. All patients had Society
      for Fetal Urology grade 3 to 4 hydronephrosis on ultrasonography and radiographic
      confirmation of UPJ obstruction by diuretic mercaptoacetyltriglycine renography.
      Pyeloplasty was performed through a flank incision. A circumferential incision
      was made of the renal pelvis proximal to the insertion site of the ureter into
      the renal pelvis. Next, a catheter was passed through the UPJ to ensure uniform
      patency. The cuff of pelvis with the attached ureter was then sutured to the
      dependent portion of the pelvis. Postoperative resolution of the obstruction was
      evaluated by ultrasonography and mercaptoacetyltriglycine renography. RESULTS: A
      total of 11 children (6 boys and 5 girls) underwent renal cuff pyeloplasty for
      UPJ obstruction due to a high inserting ureter. Median patient age was 6 months
      (range 2.5 months to 2.4 years) and median followup was 11 months (8 months to
      3.4 years). All patients were discharged home within 2 days postoperatively. No
      intraoperative or postoperative complications were noted. All patients exhibited
      resolution of UPJ obstruction on followup radiographs. CONCLUSIONS: Renal pelvis
      cuff pyeloplasty is a surgical technique for UPJ obstruction resulting from a
      high inserting ureter without intrinsic ureteral obstruction. The procedure was
      straightforward with good results and without complications in this initial
      experience.

PMID- 16094066
TI  - Bilateral dismembered laparoscopic pediatric pyeloplasty via a transperitoneal 4
      port approach.
AB  - PURPOSE: Laparoscopic pyeloplasty is gaining acceptance for the treatment of
      ureteropelvic junction obstruction in the pediatric population, with success
      rates approaching those of traditional open pyeloplasty. We report our technique
      with a transperitoneal 4-port approach and positioning method, allowing bilateral
      laparoscopic dismembered pyeloplasty with 1 uninterrupted sterile field.
      MATERIALS AND METHODS: Two children were diagnosed with bilateral ureteropelvic
      junction obstruction. Following cystoscopic ureteral stent placement operative
      positioning was achieved with intravenous pressure infuser bags placed under each
      side of the patient and rotation of the table to a lateral decubitus position.
      Four-port transperitoneal access was used to perform bilateral dismembered
      pyeloplasty with interrupted 6-zero polyglactin sutures. RESULTS: Both patients
      had bilateral crossing vessels to the lower pole of the kidneys. Total operative
      time was 268 minutes and 284 minutes for the 8-year-old and the 14-year-old,
      respectively. The ureteral stents were removed separately at 6 and 8 weeks after
      repair with the patients under sedation. CONCLUSIONS: Bilateral laparoscopic
      pyeloplasty appears feasible for the pediatric patient.

PMID- 16094067
TI  - Psychosocial and psychosexual development in childhood and adolescence within the
      exstrophy-epispadias complex.
AB  - PURPOSE: We report the psychosocial and psychosexual development of children and
      adolescents with the exstrophy-epispadias complex (EEC) after complete functional
      repair using the Erlangen single stage technique. MATERIALS AND METHODS: In a
      long-term retrospective followup of an average of 11.1 years 100 patients with
      EEC (76 boys and 24 girls, mean age 14.5 years) were evaluated with respect to
      medical history, and received a general questionnaire concerning their social and
      psychosocial situation. A total of 54 patients who were 15 years or older (mean
      age 18.5) received an additional questionnaire to assess detailed sexual history.
      RESULTS: Of the patients 81% returned the general questionnaire within 3 weeks.
      School education level and social integration were high. In about 25% of the
      patients impairment of daily life was significant, and in 58.7% peer relations
      were altered. Of the adolescent group 76% answered the special questionnaire.
      Genital satisfaction and genital touching were rated low, and avoidance of nudity
      in public areas was common. All patients expressed heterosexuality and 43.9% had
      engaged in sexual intercourse but 58.5% displayed anxiety about sexual activity.
      It is noteworthy that 93.9% expressed an interest in psychological assistance.
      CONCLUSIONS: Despite a high degree of social integration and adult adaptation,
      children and adolescents with EEC suffer from psychosocial and psychosexual
      dysfunction requiring special questionnaires for adequate assessment. Anxiety
      about genital appearance and sexual activity is a common phenomenon among
      adolescents with EEC, even when they present with nearly "normal" genitalia and
      participate with satisfaction in sexual activity. Further studies are needed to
      understand the exstrophy problem and supply all patients with EEC with the
      individual care they need.

PMID- 16094068
TI  - Surgical repair of bladder exstrophy in the modern era: contemporary practice
      patterns and the role of hospital case volume.
AB  - PURPOSE: Bladder exstrophy is a rare condition, and data are lacking regarding
      practice patterns in its surgical management. We used a large nationwide database
      to investigate practice patterns of bladder exstrophy repair. MATERIALS AND
      METHODS: We used the Nationwide Inpatient Sample (1988 to 2000) to identify
      patients who underwent surgical repair of bladder exstrophy (International
      Classification of Disease-9 code 578.6). We analyzed factors affecting practice
      patterns and outcomes. Hospital volume was based on caseload during the highest
      volume year of study participation (high volume 5 or more, mid volume 3 to 4 and
      low volume less than 3 cases). RESULTS: We identified 407 cases. Approximately
      half of the patients (53.2%) were hospitalized within 24 hours of birth, although
      28% of patients were older than 1 year. Of the patients 54% were male. Exstrophy
      repair is extremely resource intensive. In this series mean length of hospital
      stay (LOS) was 24.6 +/- 22.8 days, and mean inflation adjusted hospital charges
      were 62,302 dollars (median 39,978 dollars). High volume hospitals (HVHs) had
      lower hospital charges (37,370 dollars) than mid volume (51,778 dollars) or low
      volume hospitals (LVHs, 50,474 dollars, p = 0.0095). On multivariate regression
      HVHs had lower charges even after controlling for other significant predictors,
      including LOS (p <0.0001). Patients at HVHs were more likely to undergo osteotomy
      (p = 0.007). Six patients died after exstrophy repair (1.5%), all of whom had
      been born prematurely (p <0.0001). Although death was more likely at LVHs, this
      was due to the fact that more patients at LVHs were born prematurely (4.2% at
      HVHs vs 5.9% at mid volume hospitals and 11.1% at LVHs, p = 0.027). CONCLUSIONS:
      Bladder exstrophy repair carries a high risk of morbidity and is resource
      intensive. Variations between high and low volume hospitals in practice patterns
      and case mix may contribute to observed differences in resource use, LOS and
      clinical outcomes.

PMID- 16094069
TI  - Laparoscopic extravesical reimplantation for postpubertal vesicoureteral reflux.

PMID- 16094070
TI  - Endopyelotomy in childhood: our experience with 37 patients.

PMID- 16094071
TI  - Alarm treatment is successful in children with day- and night-time wetting.

PMID- 16094072
TI  - Effect of alarm treatment on bladder storage capacities in monosymptomatic
      nocturnal enuresis.

PMID- 16094073
TI  - Unusual female suburethral mass lesions.

PMID- 16094074
TI  - Renal gastric fistula caused by staghorn calculus.

PMID- 16094075
TI  - Potassium-titanyl-phosphate laser laparoscopic partial nephrectomy without hilar
      clamping in the survival calf model.
AB  - PURPOSE: Laparoscopic partial nephrectomy (LPN) with hilar clamping represents
      the various challenges associated with warm ischemia. We tested the feasibility,
      and acute and chronic outcomes of LPN using a potassium-titanyl-phosphate (KTP)
      laser without vascular hilar clamping in the survival calf model. MATERIALS AND
      METHODS: Six Jersey calves weighing 76 to 94 kg underwent a total of 12 staged
      bilateral transperitoneal laser LPNs of the mid/lower pole using an 80 W KTP
      laser, including left kidney chronic LPN with 1-month followup in 6 and right
      kidney acute LPN with immediate sacrifice in 6. Two techniques (ablative
      vaporization in 5 subjects and wedge resection in 7) were evaluated. Renal
      parenchymal resection and hemostasis were achieved only with the laser without
      any adjunctive hemostatic sutures or bioadhesives. Retrograde pyelography, renal
      arteriography and histological analyses were performed. RESULTS: All 12
      procedures were successful performed laparoscopically without open conversion and
      11 (92%) were done without hilar clamping. Mean total operative time was 2.9
      hours (range 1.5 to 5) and mean blood loss was 119 cc (range 25 to 300). Mean
      lasing time was 56 minutes (range 20 to 100) with an average energy use of 54 kJ.
      Mean preoperative and postoperative hemoglobin (10.38 and 10.52 gm/dl) and serum
      creatinine (0.46 and 0.4 gm/dl, respectively) were similar. At 1-month followup
      there was no evidence of urinary leakage or arteriovenous fistula. CONCLUSIONS:
      This initial study of laparoscopic KTP laser partial nephrectomy without hilar
      clamping confirms its technical feasibility in most cases and good short-term
      outcomes. This success of laser LPN in the robust survival calf model with its
      human-sized kidney holds promise for future clinical application.

PMID- 16094076
TI  - Inhibition of tumor implantation by intravesical gemcitabine in a murine model of
      superficial bladder cancer.
AB  - PURPOSE: We determined if a single intravesical instillation of gemcitabine
      (2',2'-difluorodeoxycytidine) could prevent the implantation of urothelial cancer
      cells in the bladder wall of mice, and if 4 weekly treatments could eliminate
      early implanted bladder cancer in this model. MATERIALS AND METHODS: Tumor
      implantation and orthotopic bladder tumors were induced in mice by electrocautery
      of the bladder wall and subsequent instillation of MB49 bladder cancer cells. In
      the first experiment the tumor cell suspension was left in place for 30 minutes,
      immediately followed by bladder irrigation and a single intravesical instillation
      of 250 or 500 microg gemcitabine for 10, 30, 60 or 120 minutes. In the second
      experiment dwell time was 2 hours, bladders were not irrigated after tumor cell
      instillation and mice were treated with 4 weekly instillations starting 24 hours
      after tumor cell implantation. The animals were monitored for side effects and
      bladder cancer signs, and autopsied at the end of followup. RESULTS: A single
      intravesical instillation of 500 microg gemcitabine (10 mg/ml) for 30 minutes
      decreased tumor outgrowth significantly from 90% (control) to 30% (chi-square
      test p = 0.022). Gemcitabine at 250 microg and prolonged instillations of 500
      microg during 60 or 120 minutes were less effective. In the second experiment a
      short dwell time (30 minutes) was effective at 500 microg doses, resulting in an
      outgrowth decrease in 89% (control) to 30% of mice, whereas longer instillations
      (greater than 120 minutes) resulted in significantly reduced tumor outgrowth (11%
      at 250 microg). The apparent loss of efficacy as a factor of time could not be
      fully explained. Prolonged bladder distention caused by increased bladder volume
      due to diuresis may have resulted in trauma and caused enhanced susceptibility to
      tumor implantation. In the second experiment prolonged instillations (greater
      than 120 minutes) at 250 microg or higher doses (500 microg) were effective with
      11% and 30% outgrowth, respectively. CONCLUSIONS: If given early (within 30
      minutes.) after tumor cell seeding, gemcitabine is effective for preventing tumor
      cell implantation and the resulting tumor outgrowth.

PMID- 16094077
TI  - Interferon-gamma up-regulates toll-like receptor 4 and cooperates with
      lipopolysaccharide to produce macrophage-derived chemokine and interferon-gamma
      inducible protein-10 in human bladder cancer cell line RT4.
AB  - PURPOSE: Previously we have reported that RT4, a well differentiated human
      bladder cancer line, increases the expression of macrophage derived chemokine
      (MDC) and interferon (IFN)-gamma-inducible protein-10 (IP-10) in response to IFN
      gamma and tumor necrosis factor (TNF)-alpha. In this study we examined the signal
      mechanisms for inducting these 2 chemokines in RT4 cells by lipopolysaccharide
      (LPS), IFN-gamma and TNF-alpha. MATERIALS AND METHODS: MDC and IP-10 expression
      was evaluated by sandwich enzyme-linked immunosorbent assay. Signal molecule
      activation was examined by Western blotting and electrophoretic mobility shift
      assay. The expression of toll-like receptor (TLR)-4 was analyzed by reverse
      transcriptase-polymerase chain reaction and flow cytometry. RESULTS: LPS did not
      induce RT4 cells to produce IP-10 and MDC. However, LPS plus IFN-gamma synergized
      the productions of the 2 chemokines. IFN-gamma up-regulated the expression of TLR
      4, which is an LPS binding receptor. Although LPS and IFN-gamma alone marginally
      activated nuclear factor (NF)-kappaB but not AP-1, LPS plus IFN-gamma augmented
      NF-kappaB and AP-1. Specific inhibition of NF-kappaB and AP-1 pathways decreased
      the production of MDC and IP-10. Extracellular regulated kinase (ERK)1/2, an
      upstream signal of AP-1, was also responsive to LPS and/or IFN-gamma. TNF-alpha
      also activated NF-kappaB, AP-1 and ERK1/2. However, TNF-alpha plus IFN- gamma was
      associated with the activation of NF-kappaB but not of AP-1/ERK1/2 for the
      induction of MDC and IP-10. CONCLUSIONS: IFN-gamma enhances LPS for the induction
      of MDC and IP-10 through up-regulation of TLR-4, and the signal pathways of NF
      kappaB and AP-1/ERK1/2. This mechanism may help us understand inflammatory
      responses of the bladder to localized bacterial infection.

PMID- 16094078
TI  - Elevation of dipeptidylpeptidase iv activities in the prostate peripheral zone
      and prostatic secretions of men with prostate cancer: possible prostate cancer
      disease marker.
AB  - PURPOSE: Dipeptidylpeptidase IV (DPIV) is a multifunctional type II plasma
      membrane glycoprotein with serine-type exopeptidase activity that is secreted by
      the prostate and increased in prostate cancer. We determined whether changes in
      DPIV activities in prostatic tissue zones and expressed secretions were
      associated with the presence of cancer. MATERIALS AND METHODS: Expressed
      prostatic secretion (EPS), and biopsy of the transition (TZ) and peripheral (PZ)
      zones were collected from men undergoing ultrasound guided prostate biopsy. DPIV
      activities were measured by glypro-p-nitroanalide hydrolysis. RESULTS: DPIV
      activities were significantly higher in TZ than in PZ tissues in men with no
      evidence of malignancy. However, activities in EPS were negatively associated
      with TZ volume and positively associated with PZ volume. Mean and median DPIV
      activities in EPS from men with biopsy determined cancer were significantly
      higher than in men with no evidence of malignancy. DPIV activities in TZ and PZ
      biopsies were higher in men with cancer but most markedly in the PZ. CONCLUSIONS:
      These data indicate that secreted DPIV originates from the TZ and PZ. Increased
      DPIV activities in cancer are strongly associated with the PZ, which is the zone
      most commonly involved with cancer. Measuring DPIV levels in expressed EPS or
      post-digital rectal prostate examination urine may be useful for evaluating men
      for prostate cancer.

PMID- 16094079
TI  - An electrified catheter to resist encrustation by Proteus mirabilis biofilm.
AB  - PURPOSE: We investigated the effect of iontophoresis produced by passing an
      electric current through silver electrodes attached to catheters on catheter
      encrustation by crystalline Proteus mirabilis biofilm. MATERIALS AND METHODS:
      Four glass bladder models were catheterized with 16Fr silicone catheters, of
      which 3 had 0.25 mm silver wires running through and beside the lumen. Two wired
      catheters had the silver wires connected to a 9 V direct current source supplying
      a steady current of 150 microA via a self-regulating circuit. Artificial urine,
      which had been inoculated with a clinical strain of P. mirabilis isolated from an
      encrusted catheter, was instilled into the bladder model at 0.5 ml per minute.
      The models were operated until the test catheters became blocked. Mean blockage
      time was statistically analyzed by ANOVA. Bacterial colony count, silver ions and
      pH were assessed every 24 hours. RESULTS: The experiment was repeated 3 times.
      Time to blockage, colony count, pH and scanning electron microscopy was used to
      assess encrustation in electrified and control catheters. Time to blockage in
      electrified vs control catheters was 156 vs 22 hours. The difference in blockage
      times was statistically significant (p <0.002). The viable bacterial cell count
      in urine with test catheters vs that in controls was 1.12 x 10(4) vs 2.73 x 10(9)
      cfu/ml. The pH increased to 9 in control models, whereas it remained less than
      6.5 in test models for about 100 hours. CONCLUSIONS: Electrified catheters
      released ions in urine that have the oligodynamic property of inhibiting
      bacterial growth. The application of electric current to catheters fitted with
      silver electrodes significantly decreased the rate at which these devices became
      encrusted by P. mirabilis. This principle could be used to prevent encrustation
      on long-term catheters.

PMID- 16094080
TI  - Novel delivery of oligonucleotides using a topical hydrogel tissue sealant in a
      murine partial nephrectomy model.
AB  - PURPOSE: Ischemia/reperfusion injury is a leading cause of renal damage and
      antisense gene therapy has been shown to ameliorate its effects. However, this
      approach has been limited by current delivery methods that require high
      concentrations of intravenous nucleic acids lacking specificity for targeting
      tissues. To overcome these limitations we developed a novel murine partial
      nephrectomy model to evaluate polyethylene-glycol (PEG) hydrogel tissue sealant
      as a topical oligonucleotide delivery system. MATERIALS AND METHODS: A total of
      18 male C57BL/6 mice underwent left partial nephrectomy with vascular occlusion.
      Hydrogel primer and then sealant were applied to the cut surface and
      photopolymerized. Using this method 16 additional mice received hydrogel primer
      mixed with Cy5 labeled fluorescent oligonucleotide (10 to 100 microg). Kidneys
      were harvested at various time points and assessed for oligonucleotide
      penetration using fluorescence microscopy. RESULTS: A survival rate of 100% (34
      subjects) was obtained using this mouse model of partial nephrectomy. PEG
      hydrogel provided adequate protection against renal hematoma and intraperitoneal
      blood. Fluorescent images revealed that 50 microg was the minimum dose resulting
      in complete progressive cellular penetration with time. In addition to direct
      diffusion from the application site, movement of oligonucleotide through the
      subcapsular space into the cortex was an observed mechanism of distribution.
      CONCLUSIONS: A murine partial nephrectomy model was successfully created using
      PEG hydrogel. In addition to achieving hemostasis, hydrogel served as a
      successful depot for delivering oligonucleotides throughout the kidney.

PMID- 16094081
TI  - Effects of the selective acetylcholinesterase inhibitor TAK-802 on the voiding
      behavior and bladder mass increase in rats with partial bladder outlet
      obstruction.
AB  - PURPOSE: We examined the effects of the selective acetylcholinesterase (AChE)
      inhibitor TAK-802 on voiding behavior and residual urine volume in rats with
      partial bladder outlet obstruction (BOO) vs rats treated with the nonselective
      AChE inhibitor distigmine and the muscarinic agonist bethanechol. In addition,
      the effect of repeat doses of TAK-802 on the bladder mass increase associated
      with BOO was also examined. MATERIALS AND METHODS: Male rats with BOO were used.
      Six to 8 days after obstruction voiding behavior was observed in a metabolic
      cage. The animals were then treated orally with 1 drug, and voiding frequency and
      urine volume at each void were measured for 3 hours. Subsequently the volume of
      urine retained in the bladder (residual urine) was measured. In another
      experiment bladder weight in rats with BOO was measured after early repeat doses
      of TAK-802. RESULTS: BOO increased voiding frequency and decreased average voided
      volume. TAK-802 and distigmine increased average voided volume, while not causing
      any change in voiding frequency. On the other hand, bethanechol increased voiding
      frequency without affecting average voided volume. While all 3 drugs
      significantly decreased residual urine volume, TAK-802 was most efficacious. In
      addition, bladder weight in the control BOO group was greater (approximately 2.2
      fold) than that in the sham operated group and early repeat administration of TAK
      802 prevented the bladder mass increase. CONCLUSIONS: AChE inhibitors decreased
      residual urine volume by restoring voiding function in rats with BOO, although
      only the effect of TAK-802 was dose dependent. Bethanechol also decreased
      residual urine volume in a dose dependent manner but by increasing voiding
      frequency. The prevention of a bladder mass increase by TAK-802 treatment may be
      attributable to its effect on restoring voiding.

PMID- 16094082
TI  - Improving erectile function by silencing phosphodiesterase-5.
AB  - PURPOSE: We investigated whether phosphodiesterase-5 (PDE5) can be down-regulated
      by a specific small interfering RNA (siRNA) and whether this would improve
      erectile function. MATERIALS AND METHODS: A PDE5 siRNA encoding oligonucleotide
      was inserted into pSUPER-retro vector, resulting in the siRNA expressing
      construct, pPDE5-silencer. The construct was packaged into oncoretroviral
      particles and then transduced into rat cavernous smooth muscle cells (CSMCs).
      Cells were examined for PDE5 expression by reverse transcriptase-polymerase chain
      reaction, Western blotting and immunofluorescence microscopy. Cells were then
      treated with 10 microM sodium nitroprusside (SNP) and examined for cyclic
      guanosine monophosphate (cGMP) at 0, 10, 30, 60 and 240 minutes. The siRNA
      expressing cassette was transferred from the oncoretrovirus to lentivirus, which
      was then injected into rat penises. Three months later erectile function was
      examined by electrostimulation and PDE5 expression in cavernous smooth muscle was
      determined by immunohistochemistry. RESULTS: CSMCs transfected with pPDE5
      silencer (CSMC plus siRNA) showed an 88.2% decrease in PDE5 compared with CSMCs
      transfected with control vector (CSMCs plus vector). Within 10 minutes of SNP
      treatment cells (CSMCs, CSMCs plus vector and CSMCs plus siRNA) showed similar
      sharp increases in cGMP. However, while cGMP levels in CSMCs and CSMCs plus
      vector returned to almost baseline in 1 hour, the cGMP level in CSMCs plus siRNA
      remained high even 4 hours after SNP treatment. Rats injected with the siRNA
      expressing lentivirus showed increased electrostimulated erectile function, as
      measured by peak intracorporeal pressure and the intracorporeal pressure
      increase, compared with rats injected with control lentivirus. PDE5 expression
      was decreased in the siRNA treated cavernous smooth muscle. CONCLUSIONS: PDE5
      expression could be decreased by siRNA, resulting in prolonged cGMP accumulation
      and improved erection.

PMID- 16094083
TI  - Mutation of the androgen receptor causes oncogenic transformation of the
      prostate.

PMID- 16094084
TI  - Estrogen receptor alpha and imprinting of the neonatal mouse ventral prostate by
      estrogen.

PMID- 16094085
TI  - Receptor binding studies disclose a novel class of high-affinity inhibitors of
      the Escherichia coli FimH adhesin.

PMID- 16094086
TI  - Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive
      immunity via a toll-like receptor-4-dependent mechanism.

PMID- 16094087
TI  - Re: Prognosis of patients with lymph node positive prostate cancer following
      radical prostatectomy: long-term results.

PMID- 16094088
TI  - Re: Bacillus Calmette-Guerin versus epirubicin for primary, secondary or
      concurrent carcinoma in situ of the bladder: results of a European Organization
      for the Research and Treatment of Cancer-Genito-Urinary Group Phase III Trial
      (30906).

PMID- 16094089
TI  - Re: Current status of local salvage therapies following radiation failure for
      prostate cancer.

PMID- 16094091
TI  - Re: Continence and classic bladder exstrophy treated with staged repair.

PMID- 16094092
TI  - Re: Pediatric ceftriaxone nephrolithiasis.

PMID- 16094093
TI  - Re: The prostate specific antigen era in the United States is over for prostate
      cancer: what happened in the last 20 years?

PMID- 16094094
TI  - Re: Ionic currents in single smooth muscle cells of the human vas deferens.

PMID- 16094095
TI  - Re: Cystectomy and orthotopic ileal neobladder: the impact on female sexuality.

PMID- 16094096
TI  - Re: The prostate specific antigen era in the United States is over for prostate
      cancer: what happened in the last 20 years?

PMID- 16094101
TI  - A model for cochlear implant electrode insertion and force evaluation: results
      with a new electrode design and insertion technique.
AB  - OBJECTIVES AND HYPOTHESIS: This study has the specific aim of evaluating the
      insertion characteristics of a new cochlear implant electrode. Techniques for
      evaluation of fluoroscopic real time mechanical insertion dynamics, histologic
      electrode position and trauma results, hydraulic force, and mechanical insertion
      forces are presented. In addition, this study should serve to present a novel
      model for cochlear implant electrode insertion evaluations. STUDY DESIGN:
      Prospective analysis using a series of analytical techniques. METHODS: All
      studies are conducted in fixed cadaveric temporal bones. Real time fluoroscopic
      insertion evaluations, histologic evaluations for trauma and electrode position
      in embedded bones, hydraulic measures, and mechanical intracochlear force
      measurements are conducted with a current and new electrode. RESULTS: The Contour
      Advance electrode provides a more reliable and less traumatic insertion when
      deployed with the Advance Off Stylet technique. This is largely because of a
      reduction in intracochlear outer wall force generation. Fluoroscopic and
      histologic analysis reveal a smooth insertion without reliance on cochlear outer
      wall contact. No hydraulic forces were detected when measured from the superior
      semicircular canal ampulla. CONCLUSION: The model used for this study provides
      valuable information to cochlear implant surgeons and design engineers. The
      Contour Advance electrode, inserted with the Advance Off Stylet technique,
      represents an improvement over the Contour electrode inserted with the standard
      insertion technique.

PMID- 16094102
TI  - Shape-memory stapes prosthesis for otosclerosis surgery.
AB  - OBJECTIVES: The aim of this study was to determine the efficacy of a shape-memory
      alloy, Nitinol, as a component of an improved stapes prosthesis. STUDY DESIGN:
      Prospective laboratory and clinical study to develop a Nitinol stapes prosthesis.
      METHODS: Various diameters of Nitinol wire and temperature transition variants
      were analyzed with regard to ease of deformation, response to heating, and
      strength. The size and geometry of the closed hook was determined by measurement
      of 50 incus cadaver bones. Several heat sources for activating the shape memory
      were evaluated, including electrocautery, lasers, and warm water. Trial surgeries
      were then performed on human temporal bones in the laboratory. The closure
      characteristics of the Nitinol loop were studied. Magnetic resonance imaging
      (MRI) testing at 1.5 Tesla was performed to determine safety during MRI studies.
      Preliminary human subject trials were then instituted. RESULTS: In all cases, a
      low heat condition was ample to activate the shape memory characteristics of the
      hook and return it to a closed position after it had been opened. Laser power was
      generally set well below the power needed for removing bone. The Nitinol loop
      closed snugly around the incus with application to the top of the hook with a low
      temperature laser setting. Almost any heat source was effective. MRI testing at
      1.5 Tesla showed no movement of the prosthesis. Preliminary results in human
      subjects showed excellent air-bone closure. The Nitinol loop holds uniform
      contact around the incus. CONCLUSIONS: The Nitinol piston greatly simplifies the
      stapedectomy procedure by taking the need for a hand operated instrument out of
      the surgeon's hands. Because of the nature of the Nitinol wire, it can never over
      crimp. All these characteristics make the prosthesis advantageous for
      otosclerosis surgery.

PMID- 16094103
TI  - A standardized regimen of antibiotics prevents infectious complications in skull
      base surgery.
AB  - OBJECTIVES/HYPOTHESIS: Craniofacial surgery has been associated with a
      significant improvement in disease outcome for patients with skull base
      neoplasms. Despite this improved survival, complications remain considerable. One
      major source of complications is infectious events. The current study was
      designed to evaluate a prospectively designed antibiotic regimen and its impact
      on the incidence and severity of infectious complications. This regimen was
      compared with a group of historic controls in which antibiotics were administered
      on an ad hoc basis. The specific objectives/hypothesis were to determine 1) the
      incidence and severity of infection in a group of patients treated with a
      nonstandardized antibiotic regimen undergoing craniofacial resection, and 2)
      whether the use of a prospectively designed, three-drug, broad spectrum
      antibiotic is associated with a reduced incidence and severity of infections.
      STUDY DESIGN: A single-arm, prospective antibiotic regimen consisting of
      ceftazidime, flagyl (metronidazole), and vancomycin (CMV) was compared with a
      historic control of patients treated with nonstandard antibiotic therapy
      (nonCMV), all of whom underwent craniofacial resection. Outcome measures focused
      on incidence of infection, severity of infection, and operative mortality.
      METHODS: In July 1990, a retrospective review (1973-1990) was performed of
      craniofacial resection. Beginning in July 1990, a prospective database (1990
      2003) has been maintained. Demographics, prior therapy, anatomic site of origin
      and extent of disease, pathology, standard surgical data, and postoperative
      therapy were detailed. Antibiotic data were collected from chart review.
      Complications, focusing on infectious complications, were identified and
      categorized. Culture results and whether the inciting infection was sensitive or
      resistant to perioperative antibiotics were noted. Length of hospital stay was
      tabulated. Disease outcome, including incidence of postoperative mortality, was
      maintained for each patient. RESULTS: A total of 211 patients underwent
      craniofacial resection from 1973 to 2003. Major medical comorbidities were
      present in 53 (25%) patients, and 96 (46%) had prior therapy. The standardized
      antibiotic therapy (CMV) was used in 90 patients, and the nonstandardized
      antibiotics (nonCMV) were used in 107 patients. Free flap reconstruction was the
      sole surgical factor associated with a marked reduction in complications.
      Infectious wound complications were 11% within the CMV group versus 29% in the
      nonCMV regimen (P = .002). Moreover, the severity of infections was greatly
      diminished in the CMV group (P = .0001). With use of a multivariate analysis, the
      only factor which was predictive of infectious complications was the use of CMV.
      Patients who received nonCMV antibiotic therapy faced a risk of infection that
      was 2.5 times higher than those who received CMV. Hospital stay in days and
      operative mortality were both adversely affected by the use of nonCMV antibiotic
      therapy. CONCLUSIONS: The data supports the hypothesis that the use of a three
      drug, broad spectrum antibiotic regimen in skull base surgery reduces the
      incidence of infectious complications and appears to reduce operative mortality.
      Broad spectrum coverage of Gram-positive, Gram-negative, and anaerobic pathogens
      leads to a marked reduction in infectious complications. Broad spectrum
      antibiotic coverage avoids many infectious complications and ultimately had a
      positive impact on patient outcome, quality of life, and, potentially, survival.

PMID- 16094104
TI  - Caspase inhibition enhances ischemic tolerance of fasciocutaneous flaps.
AB  - OBJECTIVES/HYPOTHESIS: To demonstrate the significance of apoptosis in ischemia
      reperfusion injury in revascularized fasciocutaneous flaps and test the
      hypothesis that pharmacologic inhibition of caspases prolongs the allowable
      primary ischemia time of these flaps. STUDY DESIGN: Animal study using the
      epigastric flap in adult male Sprague-Dawley rats. METHODS: Fifty-nine rats were
      treated with the caspase inhibitor (Q-VD-OPH) reconstituted in dimethylsulfoxide
      (DMSO) (n = 20, 8 mg/kg:0.8 mL/kg), DMSO alone (n = 19, 0.8 mL/kg), or saline (n
      = 20, 0.8 mL/kg). Treatment was given as a single intraperitoneal injection 30
      minutes before starting primary ischemia. Epigastric flaps were subjected to
      increasing ischemia times followed by reperfusion. The flaps were harvested and
      analyzed 7 days later, and viability was assessed. Probit statistical analysis
      was used to determine the critical ischemia time. This was defined as the time
      point when 50% of the flaps in each group were expected to survive. RESULTS: The
      calculated critical ischemia times were 8.92 hours (95% confidence interval 7.19
      10.47 h) for the saline group, 16.35 hours (95% confidence interval 11.82-19.89
      h) for the DMSO group, and 21.73 hours (95% confidence interval 19.39-25.37 h)
      for the DMSO with Q-VD-OPH group. These differences were significantly different
      from each other. CONCLUSIONS: Pretreatment of fasciocutaneous flaps with a free
      radical scavenger alone or in combination with a caspase inhibitor significantly
      increases the flap's tolerance of primary ischemia. The added benefit of the
      caspase inhibitor suggests that apoptosis plays an important role in ischemia
      reperfusion injury in soft tissue flaps.

PMID- 16094105
TI  - Perioperative parathyroid hormone assay for diagnosis and management of
      postthyroidectomy hypocalcemia.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to assess the relationship
      between perioperative changes in parathyroid hormone (PTH) level and the
      likelihood of postthyroidectomy hypocalcemia. STUDY DESIGN: In a series of 78
      patients undergoing total or completion thyroidectomy, PTH levels were measured
      before surgery and at 10 minutes after removal of the thyroid gland. METHODS: A
      prospective, nonrandomized collection of serum from 78 consecutive total or
      completion thyroidectomy procedures performed by a single surgeon was carried out
      over 18 months. Analysis is made of PTH levels, serum calcium values, need for
      calcium supplementation, and symptoms of hypocalcemia. RESULTS: Both a PTH change
      of 75% and an absolute postoperative PTH of 7 pg/mL are accurate standards for
      predicting symptomatic hypocalcemia after total or completion thyroid surgery.
      CONCLUSIONS: Perioperative PTH levels are a tool for the prediction of
      postoperative symptomatic hypocalcemia after thyroidectomy. A PTH level drawn 10
      minutes after removal of the thyroid predicts the likelihood of postoperative
      hypocalcemia.

PMID- 16094106
TI  - Differential penetration of ototopicals and water through tympanostomy tubes.
AB  - OBJECTIVE: To evaluate the penetration of ototopicals and water through
      tympanostomy tubes (TT) using a physical model. STUDY DESIGN: An in vitro model
      was created to measure the ability of various solutions to penetrate a variety of
      TT. METHODS: A TT was placed through a perforation (myringotomy) in a silastic
      sheet (tympanic membrane) fixed between the ends of two 1 mL syringes.
      Measurements were obtained of the maximum height various liquids (tap water, 2%
      soapy water, ocean water, ofloxacin otic, corticosporin otic, and
      ciprofloxacin/dexamethasone otic) achieved before penetrating different TTs (1.0
      mm or 1.27 mm Paparella silicone, 1.14 mm or 1.27 mm Reuter Bobbin titanium, 1.27
      mm Collar Button fluoroplastic or 1.14 mm T-type silicone). RESULTS: Two percent
      soapy water was significantly more permeable than water and ocean water in all
      tubes studied. Ciprofloxacin/dexamethasone otic was significantly more permeable
      than tap water, ocean water, and ofloxacin otic in only the Collar Button
      fluoroplastic TT. Our results suggest that titanium TTs are more permeable than
      other TT. Otherwise, ototopicals, tap water, and ocean water behaved similarly
      across all TT studied. CONCLUSIONS: Our results demonstrate that ototopicals, tap
      water, and ocean water behave similarly with regard to TT penetration.
      Ciprofloxacin/dexamethasone otic may have better penetration than other
      ototopicals. Titanium TT may be easier to penetrate than other TT.

PMID- 16094107
TI  - Effect of comorbidity on quality of life and treatment selection in patients with
      squamous cell carcinoma of the head and neck.
AB  - OBJECTIVES: Comorbidity is significantly associated with diminished survival and
      quality of life (QOL) after treatment of head and neck squamous cell carcinoma
      (HNSCC). We sought to determine whether comorbidity influenced pretreatment QOL
      scores and treatment selection in patients with HNSCC. METHODS: The medical
      records of all patients diagnosed with HNSCC who participated in pretreatment QOL
      analysis over a 15-month period were retrospectively reviewed. Patients with a
      history of prior treatment for head and neck cancer, unresectable, or distant
      metastatic disease were excluded. The University of Washington (UW) QOL
      questionnaire, Performance Status Scale (PSS), and Karnofsky score were used to
      measure pretreatment QOL. Comorbidity was graded using the Modified Medical
      Comorbidity Index. RESULTS: Of 75 patients who met study criteria, 33 underwent
      primary surgical therapy, and 42 underwent nonoperative (radiation or
      chemoradiation) therapy. Treatment groups did not differ with respect to patient
      demographics, UW QOL scores, PSS scores, Karnofsky score, or comorbidity.
      Treatment groups differed significantly by disease stage and primary site.
      Patients with advanced stage disease (III/IV) or oropharyngeal primary tumors
      were more likely to undergo nonoperative treatment, compared with patients with
      early stage disease (I/II) or oral cavity primary tumors (P < .005). No
      significant association was found between comorbidity and pretreatment QOL
      scores. CONCLUSIONS: Comorbidity was not significantly associated with treatment
      selection or pretreatment QOL scores in patients with HNSCC. Location of the
      primary tumor and disease stage were significantly associated with treatment
      selection. Further studies are required to determine the effect of comorbidity on
      patient and tumor responses to treatment.

PMID- 16094108
TI  - Cochlear implantation in deaf infants.
AB  - OBJECTIVES: With the application of universal newborn hearing screening programs,
      a large pool of newly identified deaf infants has been identified. The benefits
      of early intervention with cochlear implants (CI) is being explored. Mounting
      evidence suggests that age at implantation is a strong predictor of language
      outcomes. However, new behavioral procedures are needed to measure speech and
      language skills during infancy. Also, procedures are needed to analyze the speech
      input to young CI recipients. STUDY DESIGN: Cohort-sequential. METHODS: Thirteen
      infants with profound hearing loss who were implanted between the ages of 6 to 12
      months of age participated in this study. Eight participated in two new
      behavioral methodologies: 1) the visual habituation procedure to assess their
      discrimination of speech sounds; 2) the preferential looking paradigm to assess
      their ability to learn associations between speech sounds and objects. Older
      implanted infants and normal-hearing infants were also tested for comparison. The
      pitch of mothers' speech to infants was analyzed. RESULTS: Patterns of looking
      times for the very early implanted infants were similar to those of normal
      hearing infants. Mothers' speech to infants with CIs was similar in pitch to
      normal-hearing infants who had the same duration of experience with sounds.
      CONCLUSIONS: No surgical or anesthetic complications occurred in this group of
      infants, and the pattern of listening skill development mirrors that seen in
      normal-hearing infants. Mothers adjust their speech to suit the listening
      experience of their infants.

PMID- 16094109
TI  - Are somatostatin analogs therapeutic alternatives in the management of head and
      neck paragangliomas?
AB  - BACKGROUND: Although mostly benign, head and neck paragangliomas require active
      management because of injury to adjacent neurovascular structures. Surgery,
      usually preceded by embolization, allows for complete tumor removal. However,
      surgery carries a significant risk of iatrogenic injury, related to tumor volume.
      Because paragangliomas express somatostatin receptors with high density, we
      investigated the effect of a long-acting somatostatin analogue (OCT-LAR) on the
      size of such tumors to reduce iatrogenic injury and related the percentage of
      tumor shrinkage to a tracer uptake index calculated on somatostatin receptor
      scintigraphy (SRS). METHODS: In eight of the first nine patients, 30 mg of OCT
      LAR was given intramuscularly every 28 days for 3 doses; one patient withdrew
      after the first dose because of side effects. Conventional imaging with computed
      tomography (CT) scan or magnetic resonance imaging plus SRS revealed 18
      paraganglioma sites. For each lesion, a tracer uptake index was calculated on
      pretreatment SRS. All 18 tumors were measured by CT scan before treatment and 1
      month after the third injection. RESULTS: The average percent tumor shrinkage was
      4.0 +/- 10.0%, and the average tumor reduction was 1.0 +/- 3.8 cm (P = .27, NS).
      Only 2 of the 18 paragangliomas shrank by more than 20%; these two tumors
      belonged to the only one secreting patient. There was no significant relation
      between tracer uptake index and tumor response. CONCLUSION: These results suggest
      1) that SRS results do not predict OCT-LAR efficacy on paraganglioma size, and 2)
      OCT-LAR is not useful in the preoperative management of paragangliomas.

PMID- 16094110
TI  - Intranasal lysine-aspirin in aspirin-sensitive nasal polyposis: a controlled
      trial.
AB  - OBJECTIVES/HYPOTHESIS: Intranasal lysine-aspirin has been used as a method of
      desensitization in patients with aspirin-sensitive nasal polyps to control their
      recurrence and prevent frequent surgical intervention. However, the studies are
      limited in number, and their design is open to criticisms. Thus, we conducted a
      controlled trial to study the clinical effectiveness of topical lysine-aspirin in
      patients with aspirin-sensitive nasal polyposis. STUDY DESIGN: Prospective,
      randomized, double blind, placebo controlled, crossover trial. METHODS: Aspirin
      sensitive patients confirmed by intranasal challenge were enrolled and randomized
      to receive 16 mg of topical lysine-aspirin every 48 hours or placebo for 6 months
      before crossover. Polyp growth and nasal and chest symptoms were monitored using
      acoustic rhinometry, nasal inspiratory peak flow, peak expiratory flow rate, and
      a daily diary of symptom scores. RESULTS: Twenty-two patients were enrolled.
      After withdrawals and drop outs, data were available on 11 patients for analysis.
      Multivariate analysis of measured parameters did not reveal a significant
      clinical benefit to patients receiving topical lysine-aspirin compared with
      placebo. Deterioration was similar while on lysine-aspirin or placebo.
      CONCLUSIONS: This is the first controlled clinical trial of topical
      desensitization in aspirin-sensitive nasal polyp patients. Despite the failure to
      demonstrate clinical benefit, tissue studies have shown a significant improvement
      at the microscopic level. Further work with larger numbers of patients along with
      conventional treatment may show a clinical improvement in these patients.

PMID- 16094111
TI  - Factors affecting cancer recurrence after microvascular flap reconstruction of
      the head and neck.
AB  - OBJECTIVE: Our objective was to determine which factors are associated with
      cancer recurrence after microvascular reconstruction of the head and neck for
      squamous cell carcinoma (SCC). STUDY DESIGN: A cohort of patients who fit the
      inclusion/exclusion criteria were identified retrospectively. METHODS: A group of
      184 patients who underwent successful surgical resection and simultaneous
      microvascular reconstruction of the head and neck for treatment of SCC were
      identified. The mean age was 60 (range 23-90) years, there were 115 males and 69
      females, and mean follow-up was 26.2 (range 1-99) months. Various factors were
      analyzed to determine whether they were associated with cancer recurrence,
      including those pertaining to 1) recipient vessel choice, 2) prior cancer
      treatment, and 3) cancer staging criteria. Statistical analysis was performed
      using SPSS statistical software. RESULTS: Overall cancer stage (P = .005), T
      stage (P = .0001), history of previous cancer treatment (P = .004), and history
      of previous chemotherapy (P = .044) were found to be statistically significant
      predictors of cancer recurrence on univariate analysis. However, on multivariate
      analysis, only T stage (P = .005) and history of previous cancer treatment (P =
      .008) remained as statistically significant predictors of cancer recurrence.
      Recipient vessel selection was not statistically associated with cancer
      recurrence. CONCLUSIONS: In our study, only T stage and a history of previous
      cancer treatment were associated with increased cancer recurrence. Neither the
      recipient vessel chosen nor its location impacted cancer recurrence. This
      suggests that recipient vessel selection and preparation for microvascular
      reconstruction do not jeopardize the adequacy of oncologic resection and are
      therefore oncologically sound.

PMID- 16094112
TI  - Methylation-associated silencing of death-associated protein kinase gene in
      laryngeal squamous cell cancer.
AB  - OBJECTIVES/HYPOTHESIS: Death-associated protein kinase (DAPK) is a Ca/calmodulin
      regulated Ser/Thr kinase that functions as a positive mediator of programmed cell
      death. It has been found that DAPK gene is frequently inactivated by its promoter
      hypermethylation in some cancers and tumor cell lines. However, it is not clear
      whether promoter hypermethylation of DAPK gene exists in laryngeal squamous cell
      cancer (LSCC). The aim of this study was to investigate the promoter methylation
      status of the DAPK gene in LSCC and the effect of 5-Aza-2'-deoxycytidine (5-Aza
      CdR), a demethylating agent, on Hep-2 cells, a human laryngeal cancer cell line,
      and on xenografts of Hep-2. METHODS: Methylation-specific polymerase chain
      reaction (PCR) and reverse-transcription PCR techniques were used to determine
      the promoter methylation status and mRNA expression of DAPK gene in LSCC.
      Furthermore, Hep-2 cells in vitro and in vivo were treated by 5-Aza-CdR to
      explore the effect of demethylating agents on DAPK mRNA expression and tumor
      growth. RESULTS: Hypermethylation of DAPK gene promoter was found in 39 (67.2%)
      of 58 LSCC samples. There was no significant difference in the promoter
      hypermethylation rate among the samples of different histologic grades or samples
      from patients with different T stages. However, there was significant difference
      in methylation status of DAPK gene between the samples from patients in N0 stages
      and those from patients in N1 stages. No promoter hypermethylation of DAPK gene
      was found in any of the five normal laryngeal tissue samples. DAPK mRNA
      expression was not detected in tumor specimens with promoter hypermethylation. On
      the contrary, DAPK mRNA expression was observed in the unmethylated tumor
      specimens, specimens from tissues adjacent to the tumor, and normal laryngeal
      tissues samples. Promoter hypermethylation of DAPK gene was found, and no DAPK
      mRNA expression was detected in Hep-2 cells. DAPK mRNA expression in Hep-2 cells
      and xenografts could be restored by treating cells and xenografts with 5-Aza-CdR.
      The tumors' xenografts, induced by way of Hep-2 cell injection in nude mice
      treated with 5-Aza-CdR, were obviously smaller than those in nude mice treated
      with phosphate-buffered saline. CONCLUSIONS: Abnormal loss of DAPK expression
      could be associated with aberrant promoter region methylation in the LSCC. 5-Aza
      CdR may slow the growth of Hep-2 cells in vitro and in vivo by reactivating tumor
      suppressor gene DAPK silenced by de novo methylation.

PMID- 16094113
TI  - Supraglottic laryngeal cancer: analysis of treatment results.
AB  - OBJECTIVE: This study reports the results of treatment for supraglottic laryngeal
      cancer with nine different treatment modalities with long-term follow-up. STUDY
      DESIGN: Retrospective study of 653 patients with supraglottic laryngeal squamous
      cell cancer treated from April 1955 to January 1999. METHODS: The study
      population included previously untreated patients with cancer of the supraglottic
      larynx treated with curative intent by one of nine treatment modalities and who
      were eligible for 5-year follow-up. The treatment modalities included subtotal
      supraglottic laryngectomy (SSL), SSL with neck dissection (SSL/ND), total
      laryngectomy (TL), TL/ND, radiation therapy (RT), SSL/RT, SSL/ND/RT, TL/RT, and
      TL/ND/RT. Multiple diagnostic, treatment, and follow-up parameters were studied
      using standard statistical analysis to determine significance. RESULTS: None of
      the nine treatment modalities produced a survival advantage, either overall or
      within the stages. Overall disease specific survival (DSS) by treatment modality
      included SSL 88.9%, SSL/ND 75.8%, TL 83.3%, TL/ND 66.7%, RT 47.2%, SSL/RT 68.9%,
      SSL/ND/RT 68.1%, TL/RT 59.3%, and TL/ND/RT 46.7%. Improved DSS and cumulative
      disease specific survival rates were associated with patients under the age of 65
      years (P = .0001), early stage disease, N0 disease (P = .0001), clear resection
      margins (P = .0094), and no recurrence (P = .0001). Posttreatment function showed
      that 90% of patients were functional in everyday life, 90.7% were eating
      satisfactorily, 91.4% were breathing naturally, and 83% of SSL patients, 85.7% of
      RT patients, and 52.8% of TL patients had "good" voices. Laryngeal preservation
      was accomplished in 86.1% of SSL patients and 72.7% of RT patients (P = .0190).
      CONCLUSIONS: No treatment modality produced a survival advantage. Because SSL
      produced the best rate of laryngeal preservation, we recommend its use in
      treating the primary in eligible patients. The importance of clear resection
      margins is stressed. Patients with N+ disease should have the neck treated.
      Patients with N0 disease may be observed safely with no loss of survival
      advantage. Because of the pattern of recurrence and the high rates of distant
      metastasis and second primary cancers, follow-up for a period of not less than 8
      years is recommended.

PMID- 16094114
TI  - Thyroplasty type I with Montgomery implant among native French language speakers
      with unilateral laryngeal nerve paralysis.
AB  - OBJECTIVE: To document the long-term results achieved with the Montgomery implant
      in 96 French speakers with a unilateral laryngeal nerve paralysis (ULNP). STUDY
      DESIGN: Retrospective series, inception cohort of 96 patients. METHODS: Data
      regarding morbidity and functional results were obtained at regular visits to our
      clinic. All patients were followed for a minimum of 6 months or until death.
      Forty-two patients had a minimum of 12 months of follow-up. Early in the study,
      36 patients were prospectively recorded under similar conditions before placement
      of the Montgomery implant and at 1, 3, 6, and 12 months postoperatively. RESULTS:
      None of the 96 patients died in the immediate postoperative period. The
      perioperative course was unremarkable in 94.8% of cases. Perioperative problems
      included failure to obtain a satisfactory phonatory result in three patients,
      difficulty to stabilize the implant posteriorly in one patient, and fracture of
      the inferior rim of the thyroid cartilage window in another patient. The primary
      immediate postoperative problem (within the first postoperative month) was
      laryngeal dyspnea, noted in four patients. According to the patient's subjective
      assessment, speech and voice was always improved in the immediate postoperative
      period. However, three patients had secondary degradation of speech and voice.
      Revision surgery under local anesthesia resulted in a 97.9% ultimate speech and
      voice success rate. According to the patient's subjective assessment, adequate
      swallowing in the immediate postoperative period was achieved in 94.2% of cases
      that had swallowing problems preoperatively. A significant statistical increase
      in the duration parameters (phonation time, phrase grouping, speech rate)
      together with a statistical significant decrease in both the jitter and shimmer
      values was noted when comparing the preoperative and the postoperative values at
      1 month. Analysis of the evolution of the speech and voice parameters at 1, 3, 6,
      and 12 months postoperatively showed a significant decrease in the fundamental
      frequency and noise-to-harmonic ratio values but did not demonstrate any
      significant differences for the other speech and voice parameters. CONCLUSIONS:
      From the reported data, we conclude that the type I thyroplasty with Montgomery
      implant insertion is a safe and reproducible method to treat ULNP. Furthermore,
      this system achieves very good and stable phonatory results. Finally, the use of
      this technique and implant system appears safe in patients from various cultures
      with ULNP from a variety of causes and severe comorbidity. Over the past decade
      at our department, this procedure progressively replaced the use of the
      intracordal injection of autologous fat injection that was initially advocated in
      patients with ULNP.

PMID- 16094115
TI  - Functional remobilization evaluation of the paralyzed vocal cord by end-to-side
      neurorrhaphy in rats.
AB  - OBJECTIVE: To investigate the value of end-to-side neurorrhaphy to treat vocal
      cord paralysis. STUDY DESIGN: A prospective study evaluating the effects of end
      to-side neurorrhaphy to treat vocal cord paralysis by means of fiberoptic
      laryngoscopy and nerve electromyography. METHODS: Thirty Sprague-Dawley rats were
      divided into experimental group 1, experimental group 2, and a control group
      randomly. Right recurrent laryngeal nerve (RLN) was incised, and the distal end
      of the RLN was anastomosed to the right phrenic nerve by end-to-side neurorrhaphy
      in experimental group 1 or by end-to-end nerve anastomosis in experimental group
      2, respectively. The adductor nerve branch of the right RLN was incised and
      anastomosed to the proximal end of the right ansa cervicalis nerve by end-to-end
      nerve anastomosis. Fiberoptic laryngoscopy and nerve electromyography were used
      to examine the vocal cord movement and nerve regeneration. RESULTS: Three months
      after operation, this effect of end-to-side neurorrhaphy created a significant
      difference compared with the end-to-end nerve anastomosis (P < .05). The end-to
      side neurorrhaphy did not lead to vocal cord movement compared with end-to-end
      nerve anastomosis. CONCLUSION: Vocal cord paralysis cannot be treated by this
      microsurgical technique.

PMID- 16094116
TI  - Creation of a cholesteatoma model using three-dimensional cultured skin
      equivalents.
AB  - OBJECTIVES/HYPOTHESIS: Recent years have seen success in establishing methods for
      cell culture that lead to the creation of a three-dimensional tissue
      architecture, and this represents a great advance for the ability to carry out
      research in vitro. Accordingly, the present studies were carried out with the
      objective of using three-dimensional cultured skin equivalents for the in vitro
      creation of a model of middle ear cholesteatoma, something that has heretofore
      been considered to be very difficult. STUDY DESIGN: A cholesteatoma model was
      created in vitro, and discussion is presented regarding the immigration theory
      and the retraction theory that have been proposed as explanations of the
      causation of cholesteatoma. METHODS: Cultured skin equivalents were prepared,
      followed by creation of an epidermal and dermal defect in them. Then, the changes
      in the epidermis were investigated histologically. In addition,
      immunohistochemical studies were performed with regard to the effects exerted on
      the epidermis when the skin equivalents were cultured in a retracted state.
      RESULTS: It was confirmed that, as a result of the defect in the epidermis and
      dermis of the cultured skin equivalents, the epidermis at the edge of the
      defective site migrated subepidermally, and a stratified structure was formed. On
      the other hand, the retraction of the epidermis and dermis exerted almost no
      effect on the epidermal cells themselves. CONCLUSIONS: These results lend
      credence to the immigration theory as an explanation of the growth of the
      epidermis from the defective site. Conversely, it was surmised that the
      retraction theory requires some other factors in addition to retraction.

PMID- 16094117
TI  - Human papillomavirus (HPV) transcripts in malignant inverted papilloma are from
      integrated HPV DNA.
AB  - OBJECTIVES: The objectives of the study were to detect human papillomavirus (HPV)
      sequences in nasal inverted papilloma (IP) lesions and to determine whether HPV
      is involved in the progression of IP to sinonasal squamous cell carcinoma (SCC).
      STUDY DESIGN: A retrospective study was performed on 14 patients diagnosed with
      IP within the last 12 years. Three of these 14 patients developed SCC. METHODS:
      Eighteen formalin-fixed, paraffin-embedded tissue blocks were obtained for these
      14 patients. After DNA extraction, polymerase chain reaction (PCR) was performed,
      followed by hybridization using HPV 6, 11, 16, 18, 31, 33, 35, 45, and 52
      specific DNA probes, in an attempt to identify HPV type in each specimen. After
      RNA extraction, the integration status of the HPV genome was evaluated based on
      the relative abundance of E7 and E5 viral transcripts, assessed by quantitative
      real-time PCR. RESULTS: HPV sequences were detected in samples from 3 of the 14
      patients with IP. Of the three patients with SCC, HPV sequences were detected in
      two patients, whereas one patient was negative for the oligoprobes tested. Of the
      11 patients diagnosed only with IP, 1 patient was positive for HPV DNA (HPV type
      11). This difference in HPV positivity between IP and SCC was not statistically
      significant (P = .09, Fisher's Exact test, two tailed). Viral transcripts were
      detected in both patients with SSC who were HPV positive. Because HPV early
      transcripts are polycistronic, loss of 3' transcript sequences (E5) and retention
      of 5' sequences (E7) indicates integration. One of the SSC containing HPV 18
      sequences showed a E7/E5 ratio of 776:1. The other SSC showed E7 transcripts and
      an absence of E5 transcripts CONCLUSION: HPV transcripts were present in SCC
      positive for HPV, and the relative level of E7 to E5 transcripts indicates
      integration of the viral genome. These findings are suggestive of HPV having an
      active role in the lesion. More extensive studies are needed to determine the
      exact role of HPV in IP and progression to SCC.

PMID- 16094118
TI  - A single therapy for all subtypes of horizontal canal positional vertigo.
AB  - OBJECTIVE: To demonstrate that a single therapy is effective for treating all
      subtypes of horizontal canal benign paroxysmal positional vertigo (HC-BPPV).
      STUDY DESIGN: Prospective study. METHODS: Patients with HC-BPPV (n = 89) were
      diagnosed when the supine to the head-lateral test resulted in geotropic or
      ageotropic bilateral horizontal nystagmus. Three subtypes of HC-BPPV were defined
      by their characteristic patterns of nystagmus as well as by their speculative
      mechanism. Canalolithiasis (Can) denotes geotropic nystagmus induced by free
      moving otoliths in the HC. Two forms of cupulolithiasis, characterized by
      otoliths attached either on the utricle-sided (Cup-U) or the canal-sided (Cup-C)
      cupula, were identified by whether ageotropic nystagmus resolved or changed to
      geotropic nystagmus on follow-up tests. Forced prolonged position (FPP), lying on
      the healthy side for 12 hours to easily move free otoliths to the utricle, has
      proven successful in treating Can. Although Cup-U and contralateral Cup-C were
      associated with the same positional nystagmus pattern, FPP with lying on the side
      of the weaker nystagmus was found to be effective treatment, as well as
      consistent with the speculated underlying mechanism. RESULTS: All HC-BPPV
      patients including 49 with Can, 11 with Cup-C and 29 with Cup-U had complete
      resolution of symptoms and positional nystagmus after less than four treatment
      sessions. CONCLUSIONS: FPP with lying on the side of the weaker nystagmus,
      combined with careful observation of nystagmus evolvement, was found to be
      effective treatment for all subtypes of HC-BPPV in this series.

PMID- 16094119
TI  - Vocal cord paralysis after laryngeal mask airway ventilation.
AB  - The laryngeal mask airway (LMA) is being used with increasing frequency since its
      introduction into the United States in 1991. Currently, the LMA is being used in
      the United States in approximately one third of all operations or greater than
      100 million surgeries. In Britain, where it was first introduced for use in 1988,
      the LMA is estimated to be used in up to 50% of cases. Not only has its use in
      elective cases increased, but the scope of indications for the LMA has also
      grown. Its use in emergent and difficult airway management has increased, and new
      LMA products have been introduced to address the limitations of the classic
      model. As the LMA has increased in popularity, however, so has the incidence of
      LMA-related complications. Cases of mucosal trauma, hematoma, tongue cyanosis,
      arytenoid dislocation, and lingual, hypoglossal, and recurrent laryngeal nerve
      paralyses have been documented in various anesthesia journals. Reports of these
      injuries are sparse in the otolaryngology literature. As otolaryngologists who
      will manage the sequelae of LMA-related injuries, we must remain cognizant of
      potential problems and their underlying mechanisms. We report a case of
      unilateral vocal cord paralysis, which required operative repair after the use of
      an LMA. We review the existing case reports, propose mechanisms of injury, and
      discuss practical applications of our findings.

PMID- 16094120
TI  - Vestibular-evoked myogenic potentials in infancy and early childhood.
AB  - OBJECTIVE: Hearing impairment and the often concurrent loss of vestibular
      function, which is rarely assessed in infants, can both impair sensory
      integration critical to the development of normal motor coordination. This study
      demonstrates, for the first time, that vestibular function in infants can be
      noninvasively assessed using vestibular-evoked myogenic potentials (VEMPs). Our
      intentions were to demonstrate that VEMPs can be reliably recorded from neonates
      and to compare neonatal VEMPs with those obtained from normal adults. STUDY
      DESIGN: Prospective cohort study. METHODS: Myogenic evoked potentials induced by
      air- and bone-conducted auditory stimuli were recorded from the
      sternocleidomastoid muscles of 12 normal neonates and 12 neonates with various
      clinical findings. These included infants with bilateral atresia of the external
      auditory canals, Treacher-Collins syndrome, and neonates who failed universal
      neonatal screening. RESULTS: With the exception of one patient with hearing loss,
      reproducible biphasic VEMPs were recorded from the sternocleidomastoid muscle of
      all the infants using loud, short tone-burst sounds. CONCLUSIONS: The VEMP has
      characteristics that differentiate it from the postauricular response and the Jaw
      reflex. The VEMPs were dominant on the side ipsilateral to the stimulated ear.
      The overall morphology of the neonatal VEMP is quite similar to that of adults.
      The major neonatal differences are a shorter latency of the n23 peak and higher
      amplitude variability. Our results suggest that recording of the VEMP in neonates
      with various audio-vestibular problems provides useful information about
      vestibular function in this population and may provide information that leads to
      better care and rehabilitation for neonates at risk of developmental and motor
      system delay.

PMID- 16094121
TI  - Prognostic variables and calcitonin in medullary thyroid cancer.
AB  - OBJECTIVES/HYPOTHESIS: Medullary thyroid cancer (MTC) is a nonepithelial,
      neuroendocrine tumor with a more aggressive clinical behavior than differentiated
      thyroid cancer. The purpose of the study was to review a single institution's
      experience with MCT since 1969. STUDY DESIGN: Retrospective cohort study.
      METHODS: A retrospective review of 30 patients treated for MTC at a tertiary care
      referral center between 1969 and 2000. There were 17 female and 13 male patients,
      median age at presentation was 38 years, and median follow-up for survivors was
      12.4 years. RESULTS: Seventy percent of patients had sporadic MTC, 6.7% had
      familial MTC, 16.7% had multiple endocrine neoplasia syndrome type IIA, and 6.7%
      had multiple endocrine neoplasia syndrome type IIB. The cumulative overall
      survival rates at 5, 10, and 20 years were 97%, 88%, and 84%, respectively;
      disease-free survival rates were 97%, 74%, and 29%, respectively. Advanced tumor
      stage (P = .014) and multiple endocrine neoplasia syndrome type IIB predicted
      decreased disease-specific survival. Variables affecting disease-free survival
      were post-thyroidectomy calcitonin level (P = .001), vascular invasion (P =
      .005), perineural invasion (P = .010), extrathyroidal extension (P < .001), and
      the presence of nodal metastases (P = .001). Locoregional control rates were 83%
      at 5 years and 70% at 10 years. Vascular invasion (P = .004), extrathyroidal
      extension (P = .008), and post-thyroidectomy basal calcitonin level (P = .003)
      predicted locoregional failure. Many patients in the series experienced prolonged
      survival despite elevated calcitonin levels. CONCLUSION: Long-term disease-free
      survival is uncommon in MTC, but the study data indicate that the majority of
      patients with MTC live for prolonged periods, despite biochemical evidence of
      persistent disease. Adverse pathological features such as extrathyroidal
      extension and vascular and perineural invasion were predictors of disease
      recurrence. The use of serum markers in the follow-up of patients with MTC must
      be interpreted within the clinical context.

PMID- 16094122
TI  - Biomechanical strength of human nasal septal lining: comparison of the
      constituent layers.
AB  - OBJECTIVE/HYPOTHESIS: Nasal septal perforation is a common complication following
      surgery involving the nasal septum. Septoplasty, septorhinoplasty, and submucosal
      resection may result in the inadvertent resection of perichondrium, which may
      predispose the patient to septal perforations. STUDY DESIGN: Controlled human
      cadaver study testing the biomechanical strength of the constituent layers of
      nasal septal lining. METHODS: Uniform samples of nasal septal mucosa,
      perichondrium, and a composite of both layers were obtained from five fresh human
      cadavers. The mechanical tensile strength of these layers was evaluated and
      compared with the Instron 4301 Mechanical Testing System (Canton, MA). RESULTS:
      Mixed-effects regression analysis demonstrated a significant difference in the
      tensile strength of the three groups (mean values +/- SD: mucosa, 662 +/- 308 g;
      perichondrium, 1370 +/- 798 g; composite, 2340 +/- 1252 g). All three pairwise
      comparisons among the three groups showed a significant difference in tensile
      strength. CONCLUSION: The perichondrial layer imparts the majority of the
      biomechanical strength to septal lining. Lining flaps containing both
      perichondrium and mucosa are stronger than flaps with either perichondrium or
      mucosa alone. Dissection in the subperichondrial plane during septal surgery
      provides a stronger septal flap and may prevent the development of nasal septal
      perforation during nasal surgery.

PMID- 16094123
TI  - Endolymphatic sac decompression as a treatment for Meniere's disease.
AB  - OBJECTIVES/HYPOTHESIS: Endolymphatic sac decompression is a surgical treatment
      option for patients with medically intractable Meniere's disease. However,
      effectiveness is debated because published data show great variability. Outcome
      based research studies are useful in incorporating the patient's perspective on
      the success of treatment. To further assess effectiveness of endolymphatic sac
      decompression, we performed a prospective study to examine both symptom-specific
      and general health outcomes. STUDY DESIGN: Prospective, observational outcome
      study. METHODS: Nineteen patients with endolymphatic sac decompression responded
      to symptom-specific questionnaires and the Medical Outcomes Short-Form 36 Health
      Survey (SF-36) before and after surgery. Follow-up ranged from 6 to 58 months
      with a mean duration of 50 months. RESULTS: Overall measures of physical health
      were significantly improved following endolymphatic sac decompression (P = .04),
      whereas overall measures of mental health were unchanged (P = .74). Role Physical
      and Social Functioning scores were significantly improved following endolymphatic
      sac decompression (P = .04 and P = .03, respectively). Study patients scored
      significantly lower (P < .05) than SF-36 normative data in 6 of 10 categories
      before endolymphatic sac decompression but patient scores were not significantly
      different from normal scores in all but one category (General Health) following
      endolymphatic sac decompression. The mean number of vertigo episodes was
      significantly reduced from an average of 8.3 times per month to an average of 2.6
      times per month following endolymphatic sac decompression (P = .006). Ninety-five
      percent of patients (18 of 19 patients) reported improvement in symptoms
      (frequency, duration, or intensity) of vertigo and 37% (7 of 19 patients)
      reported complete resolution of vertigo. CONCLUSION: Endolymphatic sac
      decompression significantly improved perception of physical health, as well as
      symptom-specific outcomes, in patients with medically intractable Meniere's
      disease.

PMID- 16094125
TI  - Angiofibrolipoma of the ear canal.
AB  - OBJECTIVES/HYPOTHESIS: Described is the first reported case of an
      angiofibrolipoma of the ear canal in a patient who presented with right-sided
      conductive hearing loss and a medial canal stenosis. STUDY DESIGN: Case report.
      RESULTS/CONCLUSION: This variant of lipoma contains mature adipocytes, blood
      vessels, and dense collagenous tissue. The physical examination can be
      misleading, and the diagnosis requires histopathological examination. The patient
      was treated with complete surgical excision, tympanoplasty, canalplasty, and skin
      grafting to the external auditory canal. His pure-tone average improved from 37
      to 11 dB, and his air-bone gap was closed completely. The lipoma has not recurred
      in the 6-month period following surgery.

PMID- 16094124
TI  - The degree and time-course assessment of radiation-induced trismus occurring
      after radiotherapy for nasopharyngeal cancer.
AB  - OBJECTIVES/HYPOTHESIS: The objectives were to measure the degree of trismus
      induced after radiation therapy for nasopharyngeal cancer and assess its progress
      over time. STUDY DESIGN: A prospective, single-armed measurement study with long
      term follow-up. METHODS: Seventeen patients with nasopharyngeal cancer treated
      between 1997 and 1999 were studied. Patients were given radiation therapy with
      bilateral parallel-opposing ports of 45 Gy, 25 fractions, then with a reduced
      volume to 68.4 to 70.2 Gy. The end point was the degree of trismus, which was
      measured by serial changes of the maximal interincisal distance (MID) at various
      specified time points before, during, and after radiation therapy. RESULTS:
      During the 9 weeks of radiation therapy there was no significant change of MID
      (normalized MID ranged from 99.8% to 97%). The rate of decrease during this
      period was 1.3% per month. After radiation therapy there was a rapid decrease of
      MID between 1 and 9 months (normalized MID values at 1 and 9 mo were 95.5% +/-
      3.1% and 74.2% +/- 5.7%, respectively). The rate of decrease during this period
      was dramatic (2.4%/mo). One year after radiation therapy, the rate of decrease
      became slower but was still measurable (0.2%/mo for the period from 12 to 24 mo).
      For the period from 24 to 48 months. the rate dropped to 0.1% per month. By the
      end of 48 months, normalized MID was 67.8% +/- 7.6%. CONCLUSION: By means of
      measurement over a period of time, it was found that patients with nasopharyngeal
      cancer had a mean decrease in initial interincisal distance of 32% at 4 years
      after radiotherapy. The trismus process evolved at different rates. It was rapid
      at 1 to 9 months after radiation therapy, then became slower and protracted over
      later years.

PMID- 16094126
TI  - Surgical utility of a new carbon dioxide laser fiber: functional and histological
      study.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to investigate the functional and
      histological properties of surgical procedures using a new carbon dioxide (CO2)
      laser fiber. STUDY DESIGN: In vitro and in vivo animal models. METHODS: In vitro
      experiments using porcine true vocal cord and arytenoid cartilage were designed
      to study the histological effects of using a photonic band-gap fiber assembly for
      CO2 laser energy delivery. Continuous and pulsed-wave settings at different
      wattages were tested. In vivo endoscopic surgery on canine larynges and buccal
      mucosa were performed to examine functional and short-term healing when
      performing photonic band-gap fiber assembly-assisted laser surgery. RESULTS: In
      vitro experiments showed consistent cutting with the photonic band-gap fiber
      assembly using either straight or 90 degrees bent-tip fibers. The surrounding
      tissue in these experiments showed little collateral thermal damage with the
      average range of thermal width from 14.1 to 18.8 microm in vocal cords and from
      5.2 to 10.5 microm in cartilage. Similarly, thermal depth ranged from 28.0 to
      350.0 microm in vocal cords and from 269.7 to 739.6 microm in cartilage. In vivo
      experiments demonstrated ease in maneuvering and flexibility for cutting. There
      was minimal blood loss, smoke plume, or carbonaceous debris. There were no
      postprocedural complications. Normal oral intake was noted on postprocedural day
      1. There was no evidence of stridor or respiratory distress. Seven days after the
      procedure, re-epithelialization was complete in the buccal incisions and nearly
      completed in the laryngeal incisions. CONCLUSION: The photonic band-gap fiber
      assembly produced reliable results in cutting with functional characteristics
      representing an improvement over current technology. The device shows promise as
      an effective tool for minimally invasive procedures that are amenable to use of
      the CO2 laser.

PMID- 16094127
TI  - Mucosal biofilm formation on middle-ear mucosa in a nonhuman primate model of
      chronic suppurative otitis media.
AB  - BACKGROUND: An increased awareness of bacterial biofilms and their formation has
      led to a better understanding of bacterial infections that occur in the middle
      ear. Perhaps the best studied pathogen for its propensity toward biofilm
      formation is Pseudomonas aeruginosa, also the primary pathogen in chronic
      suppurative otitis media (CSOM). OBJECTIVE: The aim of this study was to
      determine whether P. aeruginosa forms a biofilm in the middle ear in the setting
      of CSOM in a nonhuman primate model. METHODS: Cynomolgus monkeys underwent
      perforation of the tympanic membrane and inoculation of the middle ear with a
      known biofilm-forming strain of P. aeruginosa. The contralateral ear was used as
      an internal control and was neither perforated nor infected. At the end of the
      study period, both ears were irrigated to remove planktonic bacteria, and the
      middle ear mucosa was removed and examined ultrastructurally using scanning
      electron microscopy (SEM) for determination of the presence or absence of biofilm
      formation. MAIN OUTCOME MEASURE: The identification of middle ear biofilm
      containing rod-shaped bacteria. RESULTS: SEM revealed that P. aeruginosa formed
      bacterial biofilm in vivo on the middle ear mucosal surface, seen only in the
      infected ear. Interestingly, biofilm formation caused by cocci was also seen in
      both the experimental as well as the control ear. CONCLUSION: P. aeruginosa forms
      biofilms in the middle ear in CSOM in primates. To our knowledge, this is the
      first report of disease-associated bacterial biofilm in a nonhuman primate model
      of CSOM. Such a model lays a foundation for much needed study into the role of
      biofilms in the pathophysiology of CSOM. Should CSOM be caused by biofilms, which
      is uncertain at this time, development of novel strategies for treatment and
      prevention may be possible. The finding of both rods and cocci forming biofilms
      also warrants further investigation.

PMID- 16094128
TI  - Sensitive pepsin immunoassay for detection of laryngopharyngeal reflux.
AB  - OBJECTIVES/HYPOTHESIS: To determine whether measurement of pepsin in throat
      sputum by immunoassay could be used as a sensitive and reliable method for
      detecting laryngopharyngeal reflux (LPR) compared with 24-hour double-probe
      (esophageal and pharyngeal) pH monitoring. STUDY DESIGN: Patients with clinical
      LPR undergoing pH monitoring provided throat sputum samples during the reflux
      testing period for pepsin measurement using enzyme-linked immunoadsorbent assay.
      RESULTS: Pepsin assay results from 63 throat sputum samples obtained from 23
      study subjects were compared with their pH monitoring data. Twenty-two percent
      (14/63) of the sputum samples correlated the presence of pepsin with LPR (pH < or
      = 4 at the pharyngeal probe), of which the median concentration of pepsin was
      0.18 microg/mL (range 0.003-22 microg/mL). Seventy-eight percent (49/63) of the
      samples unassociated with (pharyngeal) reflux contained no detectible pepsin.
      Mean pH values for pepsin-positive samples were significantly lower than negative
      samples at both esophageal probe (pH 2.2 vs. pH 5.0) (P < .01) and the pharyngeal
      probe (pH 4.4 vs. pH 5.8) (P < .01). When the pepsin assay results were compared
      with the pharyngeal pH data for detecting reflux (events pH < or = 4), the pepsin
      immunoassay was 100% sensitive and 89% specific for LPR. CONCLUSIONS: Detection
      of pepsin in throat sputum by immunoassay appears to provide a sensitive,
      noninvasive method to detect LPR.

PMID- 16094129
TI  - Molecular prognosticators and genomic instability in papillary thyroid cancer.
AB  - OBJECTIVES/HYPOTHESIS: Tumor progression has been attributed to the accumulation
      of DNA damage concurrent with selection of advantageous mutations; this DNA
      damage may result from failure to maintain genomic integrity or from
      susceptibility to carcinogens. Glutathione S-transferases (GSTs), enzymes that
      metabolize many carcinogens, may play a role in preserving genome integrity. The
      objectives of this study are to assess the relationship of GST genotypes with
      prognosis, clinicopathologic parameters, and genomic instability in papillary
      thyroid cancer. STUDY DESIGN: Prospective analysis. METHODS: GSTM1 and GSTT1
      genotypes of 35 matched normal and papillary thyroid cancer specimens were
      determined by polymerase chain reaction (PCR) using primers specific for the
      coding sequences of each gene. Genomic instability was measured by intersimple
      sequence repeat PCR for each tumor/normal pair and compared with the GAMES
      prognostic scoring system and clinicopathologic parameters including age,
      extrathyroidal extension, tumor grade, size, stage metastasis, sex, and smoking
      history. RESULTS: GSTM1 and GSTT1 null genotypes were found in the normal tissues
      of 46% and 45%, respectively. No gene losses were detected in the tumor
      specimens. A significant association between the GSTM1 null genotype and
      increased risk of recurrence and death was observed. Elevated GII correlated with
      smoking and tumor stage but not with GST genotype. CONCLUSION: The association of
      GSTM1 null genotype with intermediate and high risk GAMES categories suggests
      that GSTM1 provides some protection against disease progression. However, this
      protection does not confer resistance to disease onset. GST genotyping may be a
      useful adjunct prognosticator with GAMES.

PMID- 16094130
TI  - Jugular foramen schwannomas: diagnosis, management, and outcomes.
AB  - OBJECTIVES/HYPOTHESIS: To describe the presentation, radiographic findings, and
      surgical management of seven patients who have been diagnosed and treated with
      jugular foramen schwannomas at the University of Utah. STUDY DESIGN:
      Retrospective chart review. METHODS: The charts of seven patients diagnosed with
      jugular foramen schwannomas were reviewed for presentation symptoms, radiographic
      findings, and physical examination findings. For the six who underwent surgical
      excision, the surgical procedure used, cranial nerve function results,
      audiometric results, perioperative complications, and other follow-up data are
      presented. RESULTS: Seven patients were identified from ages 24 to 69 years. Six
      of the seven underwent surgical excision. Primary presentation symptoms included
      dizziness, hearing loss, dysphagia, diplopia, tongue paresis, and hoarseness. The
      choice of surgical approach was based on the size and location of the tumor. All
      patients had complete excision of their tumors. The nerve of origin included the
      glossopharyngeal, vagus, and spinal accessory nerves. Preoperative cranial nerve
      dysfunction continued postoperatively for lower cranial nerves but resolved in
      patients who were noted to have preoperative dysfunction of cranial nerve V and
      VI. The rate of new lower cranial nerve injury was 15% and was only seen in the
      cranial nerves that were determined to be the nerve of origin. In two cases, a
      temporary feeding tube was required. No recurrences have been noted to date.
      CONCLUSIONS: Jugular foramen schwannomas can be successfully diagnosed
      preoperatively with computed tomography and magnetic resonance imaging. These
      tumors can be successfully managed with surgery and low morbidity.

PMID- 16094131
TI  - Body fat composition: a predictive factor for obstructive sleep apnea.
AB  - OBJECTIVE: To investigate body fat composition, measured by bioelectrical
      impedance assay (BIA), for predicting the presence and severity of obstructive
      sleep apnea-hypopnea syndrome (OSAHS). Body fat composition was also compared
      with other well-known OSAHS predictors such as body mass index (BMI), neck
      circumference, and abdominal visceral fat. STUDY DESIGN: A prospective study was
      designed. Fifty-one patients (41 male, 10 female), who were referred to Hacettepe
      University Faculty of Medicine, Department of Otorhinolaryngology, Head and Neck
      Surgery with suspected OSAHS, between April 2003 and June 2004, were included in
      the study. METHODS: All patients underwent polysomnography (PSG) and were
      classified according to their apnea-hypopnea index (AHI) into four groups. The
      cross-sectional area of abdominal visceral fat was measured by computed
      tomography (CT) scanning in 33 of the patients. Neck circumference and BMI was
      measured for all patients. BIA was performed to determine body fat composition.
      The groups were compared, and correlation of the variables with AHI was
      investigated. RESULTS: Of the variables, BMI and percentage of body fat
      (determined by BIA) were found to be significantly correlated with AHI (r =
      0.782, r = 0.647). CT of cross-sectional area of abdominal visceral fat provided
      100% sensitivity and specificity (P < .001) in differentiating simple snorers
      from OSAHS patients. By combining percentage of body fat and body fat mass,
      higher levels of sensitivity (95%) and specificity (100%) were achieved for
      diagnosis of OSAHS. CONCLUSION: It was concluded that the BIA could be an
      inexpensive and practical alternative to prePSG screening tests and should be
      included in the evaluation of OSAHS patients.

PMID- 16094132
TI  - The magnanimous professional life and tragic demise of J. H. Douglas, MD.
AB  - OBJECTIVES/HYPOTHESIS: Many of the hallmarks of a very successful medical career,
      such as recognition as a leader in a field of medicine, making important
      contributions to medical knowledge of the day, and a steadfast dedication to
      patient care, had already been achieved by Dr. John Hancock Douglas. Therefore,
      the mystery surrounding his dismissal from membership of the newly formed
      American Laryngology Society (now the ALA) and his tragic demise stand in stark
      contrast. We discuss the model professional life and mysterious but tragic final
      days of this very important laryngologist of the 19th century. STUDY
      DESIGN/METHODS: A historical vignette. RESULTS: Dr. Douglas's professional
      qualities of leadership of the American Sanitary Commission, his various
      contributions to the advancement of medical knowledge during that era, and his
      steadfast dedication to the care of his patients represent highlights of a very
      honorable professional career. His final demise, bankrupt, in an ill state of
      health, and stripped of his professional appointment to the ALA, seems an unjust
      end to the life of this notable and magnanimous laryngologist. CONCLUSIONS: We
      offer this historical review of the life and demise of Dr. John H. Douglas as a
      tribute to this important figure in our profession's history.

PMID- 16094133
TI  - Limited use of complementary and alternative medicine in Israeli head and neck
      cancer patients.
AB  - HYPOTHESIS/OBJECTIVE: The use of complementary or alternative medicine (CAM) is
      growing among cancer patients. A Medline search failed to reveal any dedicated
      report of CAM use specifically in patients with head and neck cancer (HNC). STUDY
      DESIGN: Use of CAM was evaluated in a cohort of treated HNC patients. METHODS:
      Patients treated for HNC were asked if they had used CAM since their diagnosis.
      Demographic data and data pertaining to mode of CAM, duration of treatment and
      effects were obtained. RESULTS: One hundred forty-three patients (mean age 61
      years) were included. Only nine patients (6.3%) reported using disease related
      CAM. This included acupuncture (4), Reiki (2), naturopathy (2), hypnosis (1),
      shiatsu (1), chiropractic treatment (1), homeopathy (1), and selenium (1).
      CONCLUSION: Contrary to the reported use, few of our HNC patients used CAM.
      Although this could be related to good caregiver-patient relationship, further
      studies in comparable populations are warranted to evaluate if this is a local or
      a pervading finding in head and neck cancer patients.

PMID- 16094134
TI  - Electrical taste thresholds established on the medial tongue using two sizes of
      electrodes.
AB  - OBJECTIVES/HYPOTHESIS: The present study determined whether a 125 mm electrode
      would produce lower and more reliable electrical taste thresholds than a 25 mm
      electrode when measurement occurred in a medial tongue region relatively sparse
      in taste bud numbers. We hypothesized this would be the case and that the
      obtained threshold values would be higher than those previously reported for
      anterior and lateral tongue regions. STUDY DESIGN AND METHODS: Sixteen college
      age subjects were tested twice, once using the 25 mm electrode and once using the
      125 mm electrode on each of two sessions separated by 2 to 16 days. The order of
      presentation of the sessions was counterbalanced across subjects. Measurement was
      confined to the medial tongue, 0.7 cm lateral to the median furrow. RESULTS: As
      hypothesized, the larger electrode resulted in lower and more reliable threshold
      values than the smaller electrode (respective median threshold values = 20.06
      microA & 33.59 microA, P = .001; respective test-retest rs = 0.78 [P < .001] and
      0.46 [P < .05]). Also as hypothesized, the threshold values were higher (i.e.,
      sensitivity lower) than previously reported for anterior and lateral tongue
      regions. CONCLUSIONS: The magnitude and reliability of electrical taste
      thresholds depends on the tongue region examined and the size of the electrodes
      used. These results suggest that relatively large electrodes should be considered
      for electrogustometric threshold testing, particularly when lingual regions not
      highly populated with taste buds are evaluated.

PMID- 16094135
TI  - Long-term clinical, audiologic, and radiologic outcomes in palate cleft children
      treated with early tympanostomy for otitis media with effusion: a controlled
      prospective study.
AB  - OBJECTIVES: The role of tympanostomy in the treatment of otitis media with
      effusion (OME) in children with palate cleft with regard to the otologic and
      audiologic outcome is controversial. Little is known about the development of the
      mastoid air cell system (MACS) in these children. STUDY DESIGN: Controlled,
      prospective. METHODS: All children born in the hospital district area of the
      Central Hospital of Central Finland during the years 1983 to 1993 with palate
      cleft were reviewed at the age of 6 months. A total of 39 patients were followed
      up for 6 years after primary tympanostomy. Otologic and audiologic data were
      collected, and the MACS size was planimetrically measured. The control group
      consisted of age-matched children without palate cleft suffering from OME and
      were identically reviewed. RESULTS: The otologic outcome was similar in the study
      group, 64.1%, and among the controls, 60.6% were healed. There were no serious
      otologic complications in the study group. The audiologic outcome was also
      similar, with a mean pure-tone average (0.5-2 kHz) of 10.5 dB and 10.9 dB for the
      corresponding groups. The initial size and growth of the MACS did not
      significantly differ between the groups. CONCLUSIONS: The prognosis of children
      with palate cleft treated with early tympanostomy is favorable and does not
      differ from children without palate cleft. Active treatment ensures normal
      hearing during the critical years of language, speech, and cognitive development
      and maintains the development of an aerated mastoid. We believe that early
      tympanostomy is the treatment of choice of OME in palate cleft children.

PMID- 16094136
TI  - Endoscopic nasopharyngectomy for patients with recurrent nasopharyngeal carcinoma
      at the primary site.

PMID- 16094137
TI  - High-quality video recording and monitoring system for endoscopes.
AB  - We have developed a new recording system for endoscope images with the popular
      mini digital video (mini DV) camera. A special adaptor screws onto the lens top,
      and either a flexible or rigid endoscope can be attached to the camera. Using
      this system, we can monitor not only the endoscopic images but also the patient's
      condition. Satisfactory images can be obtained even with the finest fiberscope.
      Nevertheless, our new system costs only USD 1,000. Therefore, the system is both
      cost-effective and useful for the outpatient clinic or casual setting or for
      house calls for the purpose of patient education.

PMID- 16094139
TI  - Primary intracranial melanocytic tumor simulating pituitary macroadenoma: case
      report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Primary intracranial melanocytic tumors are rare
      lesions, sellar ones being even more exceptional. So far, six melanomas and two
      melanocytomas have been described in an intrasellar and/or suprasellar location.
      CLINICAL PRESENTATION: We report on the case of a 25-year-old Caucasian woman
      presenting with a 4-year history of amenorrhea and an intrasellar mass with
      suprasellar extension suggestive of a pituitary macroadenoma. INTERVENTION: A
      gross subtotal resection of a hemorrhagic tumor was performed. Histological
      examination revealed melanin-laden pleomorphic tumor cells that tested positive
      for HMB-45 and S-100 and negative for cytokeratins, thus demonstrating that the
      tumor was a melanocytic neoplasm. An extensive workup failed to find evidence of
      any other primary site. The patient received no further treatment and is alive
      and well after 24 months of follow-up. CONCLUSION: Primary sellar melanocytic
      neoplasms are extremely rare lesions and present with few differential diagnoses.
      Deciding whether the tumor is best classified as a melanocytoma or a melanoma may
      prove difficult. Wide histological variations in both melanocytomas and melanomas
      render careful consideration of the clinical, radiological, and gross features
      essential in distinguishing one from the other.

PMID- 16094140
TI  - Intrinsic hematoma of the oculomotor nerve: case report and review of the
      literature.
AB  - OBJECTIVE AND IMPORTANCE: Intrinsic oculomotor nerve hematoma is an exceptional
      cause of third nerve palsy. This case report illustrates the clinical,
      radiological, and intraoperative relevance of this rare pathological finding.
      CLINICAL PRESENTATION: A 25-year-old woman with a 12-year history of gross total
      resection of cerebellar medulloblastoma and posterior whole-brain radiotherapy
      presented with complete left oculomotor palsy. Magnetic resonance imaging
      revealed a left-sided, perimesencephalic cistern, small, round lesion with a
      fluid level. Digital subtraction angiography demonstrated no evidence of vascular
      abnormalities. INTERVENTION: A pterional craniotomy was performed, and the left
      oculomotor nerve was exposed. A blackish intrinsic lesion was detected in its
      cisternal segment near the uncus. The lesion was incised, and liquid compatible
      with a subacute noncoagulated hematoma was drained. Three months after surgery,
      the patient had partial recovery from diplopia and extraocular muscle function.
      CONCLUSION: We reviewed the literature and found four cases of oculomotor nerve
      intrinsic hematoma. These cases were all associated with hematological diseases,
      trauma, or solid tumors, and, as a group, these patients had poor outcomes. In
      the present report, the possibility of radiotherapy-induced vasculopathy as a
      predisposing factor is discussed. Surgical removal of an intrinsic nerve hematoma
      is probably helpful in the functional recovery of these patients.

PMID- 16094141
TI  - Chiari type I malformation presenting as hemifacial spasm: case report.
AB  - OBJECTIVE AND IMPORTANCE: We report on a patient with a Chiari I malformation
      presenting with right hemifacial spasm. Clinicians should consider the downward
      displacement of the hindbrain as a rare cause of hemifacial spasm in Chiari I
      malformation. CLINICAL PRESENTATION: An 18-year-old man was admitted with right
      hemifacial spasm. The results of the neurological examination were normal except
      for the facial spasm. Magnetic resonance imaging demonstrated a Chiari I
      malformation without syringomyelia. After surgery, the hemifacial spasm
      completely resolved. INTERVENTION: Posterior fossa decompression, C1 laminectomy,
      and duraplasty were performed. CONCLUSION: The hemifacial spasm could be
      attributed to compression and/or traction of the facial nerve because of downward
      displacement of the hindbrain in Chiari I malformation. Compression and/or
      traction might create irritation of the facial nerve that causes hemifacial
      spasm. Resolution of the hemifacial spasm after posterior fossa decompression
      could explain the facial nerve irritation in Chiari I malformation. Clinicians
      should consider Chiari malformation as a cause of hemifacial spasm and posterior
      fossa decompression as a potential treatment.

PMID- 16094142
TI  - Primary extradural epithelioid leiomyosarcoma of the cervical spine: case report
      and literature review.
AB  - OBJECTIVE AND IMPORTANCE: No case of primary epithelioid leiomyosarcoma involving
      the spine has been reported previously. CLINICAL PRESENTATION: A 61-year-old
      Nigerian woman presented with progressive spastic quadriparesis and acute urinary
      retention. Her only medical history included a total abdominal hysterectomy for
      fibroids 10 years earlier in Nigeria. Results of the general examination were
      normal. Pyramidal spastic quadriparesis (3/5) with a sensory level at C5-C6 was
      found neurologically. Magnetic resonance imaging scans of the brain and spine
      revealed extradural cord compression at C3-C5 as the sole abnormality. This was
      caused by a large, soft tissue mass arising from the erector spinae muscles,
      which was predominantly isointense on T1-weighted images, of mixed intensity on
      T2-weighted images, and homogenously enhanced after gadolinium contrast agent
      administration. There was an associated signal change in the cord at C3-C4.
      Computed tomography confirmed the predominantly soft tissue involvement, but with
      bone erosion and infiltration within the posterior elements of C4. Systemic
      screening for cancer was negative. INTERVENTION: At decompressive laminectomy,
      urgently undertaken under corticosteroid cover, an excessively vascularized, soft
      tissue tumor was subtotally excised, after which independent walking and normal
      sphincter function were regained within 1 week. Four weeks later, a complete
      macroscopic tumor excision was undertaken, incorporating lateral mass (C3-C6) and
      C2 pedicle screw stabilization, along with iliac crest bone grafting. The
      patient's neurological status continued to improve. However, while awaiting
      radical radiotherapy, the patient declined further treatment and returned to her
      native Nigeria. Histopathological findings were consistent with an epithelioid
      leiomyosarcoma. CONCLUSION: This is the first reported case of a primary
      craniospinal epithelioid leiomyosarcoma.

PMID- 16094143
TI  - Myxopapillary ependymoma and fatty filum in an adult with tethered cord syndrome:
      a shared embryological lesion? Case report.
AB  - OBJECTIVE AND IMPORTANCE: Myxopapillary ependymoma and fatty fila are
      traditionally thought to arise via completely different pathophysiologies.
      Recognition of these distinct pathologies in the same patient is important for
      appropriate treatment and prognosis. CLINICAL PRESENTATION: A 28-year-old woman
      presented with low back pain, bilateral leg radiculopathies, and mild leg
      weakness suggestive of tethered cord syndrome. Magnetic resonance imaging
      revealed lesions in the area of the conus medullaris consistent with a
      myxopapillary ependymoma and fatty filum. INTERVENTION: Under the surveillance of
      intraoperative electromyographic monitoring, the patient underwent an L4-S2
      laminectomy for transection of the fatty filum and gross total resection of the
      mass. Histopathological examination confirmed the presence of these two distinct
      pathologies. CONCLUSION: We report an unusual case of a myxopapillary ependymoma
      coexisting with a fatty filum in an adult patient. To the best of our knowledge,
      this association has not yet been reported. This raises the interesting question
      of a possible associative or causative relationship between these distinct
      pathologies, which have traditionally been thought to arise from different
      mechanisms.

PMID- 16094144
TI  - Endovascular management of ventricular catheter-induced anterior cerebral artery
      false aneurysm: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: We describe the case of a 3.3-kg infant who developed
      an anterior cerebral artery pseudoaneurysm after ventricular catheter placement.
      The lesion was treated with endovascular vessel sacrifice. CLINICAL PRESENTATION:
      A 3.3-kg infant with a myelomeningocele underwent repair and ventricular catheter
      insertion for hydrocephalus. During shunt insertion, intracerebral arterial
      bleeding was encountered. Subsequent arteriography demonstrated an anterior
      cerebral artery pseudoaneurysm. TECHNIQUE: Via a transfemoral artery approach,
      the aneurysm and feeding vessel were catheterized with a microcatheter and wire.
      The aneurysm and vessel were then sacrificed with detachable platinum coils.
      CONCLUSION: Arterial injury is uncommon after ventricular catheter placement.
      When it does occur, however, an unstable pseudoaneurysm may form. Endovascular
      techniques can be used to remedy this problem, thus at times obviating the need
      for a standard craniotomy, which can be particularly difficult in a newborn.

PMID- 16094147
TI  - Hyperosmolar agents in neurosurgical practice: the evolving role of hypertonic
      saline.
AB  - Medical management of cerebral edema and elevated intracranial pressure (ICP) is
      a critical component of perioperative care in neurosurgical practice. Traumatic
      brain injury, arterial infarction, venous hypertension/infarction, intracerebral
      hemorrhage, subarachnoid hemorrhage, tumor progression, and postoperative edema
      can all generate clinical situations in which ICP management is a critical
      determinant of patient outcomes. Although osmotic agents are among the most
      fundamental tools to control ICP, prospective data to establish clear guidelines
      on their use are lacking. Hypertonic saline is emerging as an alternative to
      mannitol. Early data suggest that indications for each agent may ultimately
      depend on ICP etiology.

PMID- 16094148
TI  - Impact of coil embolization on overall management and outcome of patients with
      aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: We report on the consequences of introducing coil embolization for the
      total management of and outcome in patients with subarachnoid hemorrhage (SAH).
      METHODS: In southern Sweden, a prospective analysis of all patients with SAH of
      verified aneurysmal origin was conducted during the 3 years when coiling was
      gradually being introduced. The incidence of acute or chronic hydrocephalus,
      vasospasm, delayed ischemic deterioration, and outcome at 3 to 6 months after
      bleeding was analyzed. RESULTS: Coiling of aneurysms was used progressively more
      compared with clipping during the study period. The number of patients subjected
      to coiling was 26 (36%) of 73 patients during calendar year 1997, 43 (53%) of 81
      patients in 1999, and 55 (74%) of 74 patients in 2001 (P < 0.0001). Gradually,
      more elderly patients were admitted during the study period. Virtually all
      aneurysms located in the posterior circulation were treated by coil embolization,
      even at the start of the study, whereas aneurysms at all other locations were
      progressively more likely to be treated similarly. The incidence of hydrocephalus
      in the acute (average for all 3 yr, 39%) or chronic (16%) phase, vasospasm as
      measured by Doppler sonography (33%), and delayed ischemic deterioration (29%),
      as well as outcome at 3 to 6 months (61% good recovery, 13% deceased), did not
      change significantly during the study. The main cause of unfavorable outcome was
      the severity of the SAH. CONCLUSION: The increasing use of coil embolization for
      ruptured aneurysms in the anterior circulation did not have any significant
      impact on the overall incidence of SAH-related complications or outcome. The main
      determinant for outcome after SAH is still the severity of the SAH.

PMID- 16094149
TI  - Aneurysmal rupture without subarachnoid hemorrhage: case series and literature
      review.
AB  - OBJECTIVE: Although an aneurysmal rupture typically presents on computed
      tomographic (CT) imaging as only subarachnoid hemorrhage (SAH), it may be
      associated with intraparenchymal hemorrhage (IPH), intraventricular hemorrhage
      (IVH), or subdural hemorrhage. On rare occasions, however, an aneurysmal rupture
      may present with IPH or IVH without SAH. METHODS: The Division of Cerebrovascular
      Neurosurgery at The Johns Hopkins Medical Institutions maintains a prospective
      database of all patients treated for intracranial aneurysms at this institution
      since 1991. Using this database, we identified patients with ruptured aneurysms
      who presented with IPH or IVH in the absence of SAH on CT imaging. RESULTS: Eight
      hundred twenty-two patients with radiographically documented ruptured aneurysms
      were admitted from January 1991 through June 2004. Of these, nine patients
      presented with IPH only, three with IPH and IVH, and one with IVH only, for a
      total of 13 cases. There were seven posterior communicating artery, four middle
      cerebral artery, one basilar apex, and one posterior cerebral artery aneurysms.
      The incidence of aneurysmal rupture with IPH and/or IVH without SAH is 1.6%
      CONCLUSION: Initial presentation of a ruptured aneurysm without SAH is rare and
      may have a multifactorial cause attributable to the timing of CT imaging,
      physiological parameters, or location of the aneurysm. Patients presenting with a
      head CT scan revealing IPH in the temporal lobe or with IVH should be considered
      for an urgent workup of a ruptured aneurysm, even in the absence of diffuse SAH.

PMID- 16094151
TI  - Serial single-photon emission computed tomographic and transcranial doppler
      measurements for evaluation of vasospasm after aneurysmal subarachnoid
      hemorrhage.
AB  - OBJECTIVE: To assess the clinical value of serial single photon-emission computed
      tomographic (SPECT) measurements after aneurysmal subarachnoid hemorrhage (SAH).
      METHODS: Thirty-two patients were studied prospectively during the first 26 days
      after SAH with repeated SPECT measurements, clinical examinations, and
      transcranial Doppler recordings. Time trends were analyzed with a general linear
      model. A final SPECT measurement was performed after 1 year. RESULTS: A mean of
      2.6 (range, 1-5) SPECT measurements revealed a significant (P = 0.001) quadratic
      curve consistent with initial hypoperfusion and then with hyperperfusion during
      the acute stage. SPECT findings were significantly associated with transcranial
      Doppler recordings (P = 0.016) and clinical assessments (P = 0.008). Patients
      fulfilling clinical and transcranial Doppler criteria for vasospasm demonstrated
      a more pronounced relative hypoperfusion-hyperperfusion time course. A
      multivariate logistic regression analysis identified SPECT measurements obtained
      during Days 7 to 14 after the SAH as the only independent predictor (beta =
      0.042, P = 0.02) for impaired perfusion after 1 year. CONCLUSION: Serial SPECT
      measurements after aneurysmal SAH demonstrate that regional changes in cerebral
      perfusion follow a nonlinear time trend, and repeated measurements are necessary.
      This observation, as well as the low feasibility of SPECT, restricts the clinical
      value of such measurements.

PMID- 16094150
TI  - The simplified acute physiology score to predict outcome in patients with
      subarachnoid hemorrhage.
AB  - OBJECTIVE: Current prognosticators for patients with subarachnoid hemorrhage
      (SAH) do not take into account signs of extracerebral organ dysfunction. This may
      explain the only moderate predictive value of these prognosticators. We assessed
      the prognostic value of the simplified acute physiology score (SAPS) II in SAH
      patients. METHODS: In a retrospective cohort study of 148 consecutive SAH
      patients, we related the SAPS II calculated within 24 hours after admission to
      clinical and initial computed tomographic imaging characteristics using the Mann
      Whitney U test. We compared the prognostic value of the SAPS II with that of the
      World Federation of Neurosurgical Surgeons score, the patient's age, and the
      amount of blood showing in computed tomographic imaging for the occurrence of
      delayed cerebral ischemia using Cox proportional hazards modeling or, for poor
      outcome (death or dependence), logistic regression modeling. RESULTS: In the
      univariate analysis, the SAPS II was the strongest prognosticator; in the
      multivariate model, the SAPS II was the only independent predictor for outcome
      (odds ratio, 1.08; 95% confidence interval, 1.06-1.11]). Patients in the highest
      tertile of SAPS II had a significantly higher risk of poor outcome than those in
      the lowest tertile (odds ratio, 30.9; 95% confidence interval, 9.9-96.7]). The
      SAPS II was also the only independent predictor for the occurrence of delayed
      cerebral ischemia (hazard ratio, 1.020; 95% confidence interval, 1.002-1.039]).
      CONCLUSION: The SAPS II is a useful and reliable prognosticator in SAH patients.
      This score may provide more information than specific SAH scales in predicting
      poor outcome or the occurrence of delayed cerebral ischemia in some
      circumstances.

PMID- 16094152
TI  - Heparin-induced thrombocytopenia Type II in subarachnoid hemorrhage patients:
      incidence and complications.
AB  - OBJECTIVE: Heparin-induced thrombocytopenia Type II (HIT II) is the autoimmune
      mediated severe form of the disease characterized by a significant reduction in
      platelets, and it carries a high risk of "paradoxical" serious thrombotic
      complications. Although HIT II has been studied in several different patient
      populations, the incidence of HIT II and the rate of thrombotic complications
      have never been reported in a neurosurgical patient population. Subarachnoid
      hemorrhage (SAH) patients, among neurosurgical patient populations, have a high
      exposure to heparin because they are in critical care units and have indwelling
      vascular catheters. In addition, the increase in neuroendovascular procedures
      with the associated use of heparinization will increase the exposure of SAH
      patients to heparin. METHODS: During a 3.5-year period (January 2000-June 2003),
      389 consecutive SAH patients were treated at our center. We retrospectively
      reviewed their laboratory data and medical records and used accepted clinical
      criteria for the diagnosis of HIT II to determine the incidence of HIT II,
      thrombotic complications, management, and outcome. RESULTS: Fifty-nine patients
      (15%) met the clinical diagnostic criteria for HIT II. The average platelet count
      nadir in the HIT II patients was 68,600 +/- 25,300/microl (mean +/- standard
      deviation). Female patients and patients with Fisher Grade 3 were more likely to
      develop HIT II (P < 0.01). Thirty-six patients (61%) underwent a
      neuroendovascular procedure. The rate of systemic thrombotic complications in the
      HIT II patients was 37 versus 7% in SAH patients without HIT II (P < 0.001), and
      the rate of new hypodensities on head computed tomographic scans was 66% in the
      HIT II patients versus 40% in the SAH patients without HIT II (P < 0.001).
      Clinical outcomes were worse in the HIT II patients. The outcome was favorable
      for 38% in the HIT II patients versus 52% in all SAH patients (P < 0.05), and
      deaths were more common (29%) in the HIT II patients than in all SAH patients
      (12%, P < 0.001). CONCLUSION: The incidence of HIT II in SAH patients at a single
      center was 15%. The SAH patients with HIT II had significantly higher rates of
      thrombotic complications, new hypodensities on head computed tomographic scans,
      more deaths, and significantly less favorable outcomes. This is the first report
      of the incidence of HIT II in a neurosurgical patient population.

PMID- 16094153
TI  - Effect of brain surgery on auditory and motor cortex activation: a preliminary
      functional magnetic resonance imaging study.
AB  - OBJECTIVE: The effect of glioma removal on blood oxygen level-dependent (BOLD)
      functional magnetic resonance imaging (fMRI) activation has not been widely
      documented. The aim of this preliminary study was to observe the effect of tumor
      resection on BOLD fMRI of the auditory and motor cortices. METHODS: Seven
      patients with gliomas underwent preoperative and early postoperative BOLD fMRI,
      and five of them underwent additional late postoperative BOLD fMRI. The auditory
      and motor cortices were localized with activation studies. A hemispheric
      activation index was used to quantify the relative extent of BOLD activation.
      RESULTS: The resection of a glioma with preoperative edema resulted in an
      increase from the preoperative to the early postoperative fMRI on auditory BOLD
      activation on the side of the tumor compared with the contralateral side. The
      same phenomenon was observed in one patient with motor BOLD activation. However,
      when no preoperative edema was present, a transient decrease in relative auditory
      BOLD activation was found. CONCLUSION: The results of this study suggest that the
      resection of a glioma with preoperative edema affecting the auditory and/or motor
      cortex may cause a transient increase in the BOLD response ipsilateral to the
      tumor. It seems that when the tumor is resected, the pressure on the brain,
      specifically on the affected auditory and/or motor cortex, decreases and the
      functional cortex becomes more easily detectable in BOLD fMRI.

PMID- 16094154
TI  - Stereotactic radiosurgery for vestibular schwannomas: analysis of 317 patients
      followed more than 5 years.
AB  - OBJECTIVE: Many investigators have reported successful treatment of vestibular
      schwannomas with gamma knife radiosurgery (GKRS). However, long-term outcomes
      should be evaluated before concluding that GKRS is truly safe and effective for
      the treatment of vestibular schwannomas. METHODS: Between May 1991 and December
      1998, 346 consecutive patients (excluding those presenting with neurofibromatosis
      Type 2) were treated with GKRS. Of these, 317 patients were assessed. Twenty-nine
      patients were lost to follow-up within 5 years. RESULTS: The median follow-up
      period was 7.8 years. Of 301 patients who underwent serial follow-up imaging, two
      (1%) experienced complete remission, 184 (61%) experienced partial remission, 93
      (31%) had stable tumors, and 22 (7%) experienced treatment failure. The actuarial
      5- or 10-year progression-free survival (PFS) rate was 93 and 92%, respectively.
      Tumors less than 15 cm3 in volume (10-yr PFS, 96%; P < 0.001) or which did not
      compress the brainstem and deviate the fourth ventricle (10-yr PFS, 97%; P =
      0.008) resulted in significantly better PFS rates. Failure of treatment usually
      occurred within 3 years. When the tumor was treated with a marginal dose of 13 Gy
      or less, the hearing preservation rate was 68%, transient facial palsy developed
      at a rate of 1%, and facial numbness developed at a rate of 2%. CONCLUSION: GKRS
      proved to be a safe and effective treatment for patients followed longer than 5
      years who presented with tumors with a volume of less than 15 cm3 and who did not
      have significant fourth ventricle deviation. Good functional outcomes were
      observed in this group of patients.

PMID- 16094155
TI  - Continuous intrathecal administration of 5-fluoro-2'-deoxyuridine for the
      treatment of neoplastic meningitis.
AB  - OBJECTIVE: Previously, we reported a good clinical treatment effect of
      intrathecal chemotherapy by repeated bolus administration of 5-fluoro-2'
      deoxyuridine (FdUrd) for neoplastic meningitis (NM). Moreover, we detected no
      side effects or neurotoxicity despite the long-term repetition of intrathecal
      administration. On the basis of these findings, continuous intrathecal
      chemotherapy (CIC) with FdUrd for patients with NM was attempted using a simple
      pump system. We evaluated the usefulness of CIC with FdUrd for the treatment of
      NM. METHODS: A total of 25 patients were enrolled in this study. FdUrd (1.0 mg/d)
      was administered using a balloon pump system. CIC was continued as long as
      possible. Eight patients received whole-brain irradiation (3 Gy x 10)
      simultaneously with CIC. The effects of the treatment were analyzed in terms of
      improvement in neurological signs and symptoms and the findings of ventricular
      and lumbar cerebrospinal fluid analysis 2 and 4 weeks after CIC was initiated and
      on magnetic resonance imaging scans 2 months after CIC began. RESULTS: No
      apparent toxicity has been observed to date. Evidence of a cerebrospinal fluid
      response was observed in 13 patients. Headache and nausea were improved in all
      patients, and cranial nerve impairment was improved in 12 patients. A magnetic
      resonance imaging response was observed in only 5 patients. Overall response was
      observed in 15 patients when cases of stable disease were excluded from the
      responding cases. Survival time from the commencement of CIC (mean +/- standard
      error of the mean) was 255 +/- 30 days in 25 patients. CONCLUSION: This therapy
      may be useful, especially as a maintenance therapy for NM.

PMID- 16094156
TI  - Cushing's disease in children and adolescents: 20 years of experience in a single
      neurosurgical center.
AB  - OBJECTIVE: This is a retrospective analysis of 25 consecutive pediatric patients
      with Cushing's disease who underwent transsphenoidal surgery performed by a
      single neurosurgeon in a specialist center during a 20-year period. This article
      discusses the presentation of Cushing's disease, the endocrinological
      investigation with particular reference to bilateral inferior petrosal sinus
      sampling (BIPSS), the operative management with reference to specific pediatric
      difficulties of the transsphenoidal approach and the use of intraoperative image
      guidance, and the analysis of these cases as regards postoperative complications
      and outcomes of this rare condition in young patients. METHODS: All patients
      underwent detailed endocrine investigation and imaging in the form of computed
      tomography and/or magnetic resonance imaging. BIPSS was performed in 19 patients
      (76%), with successful lateralization of the side of the microadenoma in 14 (74%)
      and prediction of a central tumor in four (94% total prediction rate). Surgical
      removal was via the sublabial, paraseptal, transsphenoidal route. RESULTS: There
      were 15 male and 10 female patients, with a mean age of 13.4 years (range, 6.6
      17.8 yr). Weight gain was the most common presentation (100%), and then growth
      impairment (96%), fatigue and skin changes (64%), and hypertension (32%).
      Postoperative complications included growth hormone deficiency (36%), transient
      diabetes insipidus (12%), panhypopituitarism (4%), and transient cerebrospinal
      fluid rhinorrhea (4%). The median follow-up period was 59.5 months (range, 6-126
      mo). Overall, 15 patients (60%) achieved surgical cure or remission, of which 14
      outcomes were obtained using the results of BIPSS. Ten patients (40%) required
      postoperative radiotherapy to achieve "remission." There were no cases of
      meningitis, no neurological deficits, no reoperations, and no mortality.
      CONCLUSION: Cushing's disease in children and adolescents is a rare illness. The
      accurate preoperative localization of the adenoma is essential for achieving good
      results. In this series, BIPSS was far more accurate in localizing the adenoma
      than computed tomography or magnetic resonance imaging. Imaging, however, is
      useful for the exclusion of other intracranial problems. Transsphenoidal surgery
      was safe and efficacious in achieving cure in the majority of cases. The
      challenge of transsphenoidal surgery in this age group is the small pituitary
      fossa and the absence of sphenoid sinus aeration in some cases. We found the use
      of intraoperative neuronavigation to be an excellent aid in overcoming such
      anatomic difficulties.

PMID- 16094157
TI  - Herniation secondary to critical postcraniotomy cerebrospinal fluid hypovolemia.
AB  - OBJECTIVE: Cerebrospinal fluid hypovolemia resulting in postural headaches is a
      well-known clinical entity, but severe forms of cerebrospinal fluid hypovolemia
      with altered mental status and signs of transtentorial herniation ("brain sag")
      have rarely been reported. This article describes the clinical features of brain
      sag after craniotomy in an attempt to increase recognition of this syndrome.
      METHODS: Between April 2001 and January 2003, 220 consecutive patients with
      subarachnoid hemorrhage were prospectively enrolled in the Columbia Subarachnoid
      Hemorrhage Outcomes Project; 137 underwent craniotomy for aneurysm clipping.
      Among these patients, the diagnosis of brain sag was made when all three of the
      following criteria were present: clinical signs of transtentorial herniation,
      head computed tomographic scans revealing effacement of the basal cisterns with
      an oblong brainstem, and improvement of symptoms after placement of the patient
      in the Trendelenburg position (-15 to -30 degrees). For each patient, the
      symptoms, clinical course, and subsequent response to treatment were
      characterized. In addition, brainstem dimensions were measured on computed
      tomographic scans taken before, during, and after resolution of brain sag. A "sag
      ratio" was generated for these time points by dividing the maximum
      anteroposterior distance by the maximum bipeduncular distance. RESULTS: Eleven
      (8.0%) of 137 aneurysmal subarachnoid hemorrhage patients treated by craniotomy
      and an intraoperative spinal drain met the criteria for brain sag. Signs of
      transtentorial herniation developed most commonly between 2 and 4 days
      postoperatively. Pupillary asymmetry was noted in 10 (91.0%) of 11 patients,
      whereas the other patient demonstrated extensor posturing. The Trendelenburg
      position reversed the symptoms in all patients. The mean sag ratios before,
      during, and after resolution of brain sag were 0.91 +/- 0.03 (mean +/- standard
      error), 1.18 +/- 0.03, and 0.91 +/- 0.03, respectively. This represented a 30.9%
      elongation of the brainstem during sag (P < 0.001) and a 23.6% change back to
      baseline after resolution of the syndrome (P < 0.002). There was no significant
      difference between the presag and postsag ratios. CONCLUSION: Severe
      cerebrospinal fluid hypovolemia after craniotomy may produce a dramatic
      herniation syndrome that is completely reversed by the Trendelenburg position.
      Brain sag should be included in the differential diagnosis for acute
      postoperative clinical deterioration in this patient population.

PMID- 16094158
TI  - Penetrating civilian craniocerebral gunshot wounds: a protocol of delayed
      surgery.
AB  - OBJECTIVE: Several factors have led to our unique approach of delayed definitive
      debridement. We wanted to evaluate the effectiveness of our management and
      compare it with the existing data in the literature. METHODS: We retrospectively
      reviewed the records of 194 patients presenting between January 1996 and October
      2003 with penetrating craniocerebral gunshot wounds. After exclusion criteria,
      125 patients qualified. RESULTS: Of the patients, 88.8% were male. The mean age
      was 24.9 +/- 10.9 years. In 70.4% of patients, the presenting Glasgow Coma Scale
      (GCS) score was 3 to 8. Only 38 (30.4%) of the 125 patients survived, with poor
      outcome in 2 and good outcome in 36. Bilaterally fixed and dilated pupils and
      bihemispheric tract on computed tomographic scan were significantly related to
      poor outcome. There were 49 surgical procedures performed on 27 of the patients,
      with a mortality rate of 7.4%. Of the 38 survivors, 13 underwent no surgery.
      Average time to surgery was 11.04 days. Total rate of infection was 8%, and it
      did not influence outcome. No patient presenting with a GCS score of 3 or 4
      survived. Seventeen patients attended follow-up, for a total of 3609 days
      (average, 212 d) and very few late complications. CONCLUSION: Our supportive care
      of patients is not optimal. We should have saved more of our patients who
      presented with GCS scores of 14 and 15 who subsequently died. We have been able
      to report unconventionally late surgical management of two-thirds of survivors,
      with no surgery in one-third of survivors. Despite a high rate of infectious
      complications, infection did not lead to death or disability. Our protocol rarely
      leads to patients surviving in a permanently vegetative state. In the future, we
      would perform early surgery for patients who present awake and continue our
      current management for poor-grade patients. In this way, we will improve the
      number of good outcomes without increasing the population of severely damaged and
      dependent survivors.

PMID- 16094159
TI  - Prolonged effects of concussion in high school athletes.
AB  - OBJECTIVE: To identify enduring prolonged neuropsychological effects of cerebral
      concussion in high school youth athletes. METHODS: High school athletes (n = 223)
      underwent baseline neuropsychological evaluation between 1999 and 2000, assigned
      to independent groups on the basis of concussion history: athletes with no
      concussion history or present medical and/or neuropsychological complaints (n =
      82), symptom-free athletes who experienced one (n = 56) or two or more (n = 45)
      concussions (not in the prior 6 mo), and those who experienced a concussion 1
      week before testing (n = 40). Main outcome measures included a structured
      clinical interview, demographic form, symptom checklist, the Repeatable Battery
      for the Assessment of Neuropsychological Status, and the Trail Making Tests A and
      B. Analyses of variance were used to determine between-group differences.
      RESULTS: Athletes with recent concussions performed significantly worse on
      measures of attention and concentration than youth athletes with no concussion
      history. Symptom-free athletes with a history of two or more concussions
      performed similar on testing to youth athletes who had just experienced a recent
      concussion. Similarly, cumulative academic grade point averages were
      significantly lower not only for youth athletes with two or more previous
      concussion groups, but for youth athletes who experienced recent concussions,
      suggesting that athletes with lower grade point averages may be more prone to
      concussion. CONCLUSION: There seem to be subtle yet significant prolonged
      neuropsychological effects in youth athletes with a history of two or more
      previous concussions.

PMID- 16094160
TI  - Cervical spondylotic myelopathy, depression, and anxiety: a cohort analysis of 89
      patients.
AB  - OBJECTIVE: To determine the prevalence of depressed and anxious mood states in
      patients with cervical spondylotic myelopathy (CSM), a degenerative spine
      condition with symptoms of neck pain, numb clumsy hands, gait difficulties,
      sphincter dysfunction, and impotence. To examine the relation between mood and
      functional deficits produced by CSM. METHODS: We surveyed a cohort of 89 patients
      with CSM recruited during 1 year from a neurosurgery clinic. Patients underwent a
      structured interview to collect information on demographics, personal habits, CSM
      symptoms, comorbid diseases, and symptoms of depression and anxiety. Patients
      self-completed the Hospital Anxiety and Depression scale and were scored on the
      Nurick, Cooper, Harsh, and modified Japanese Orthopaedic Association (mJOA)
      scales. RESULTS: According to the Hospital Anxiety and Depression scale threshold
      value of 11, 29% of the cohort had a depressed mood and 38% had an anxious mood.
      Higher depression scores were associated with worse myelopathy, as measured by
      the Nurick scale (P = 0.01), the Cooper leg subscale (P = 0.006), the Harsh scale
      (P = 0.02), the mJOA arm subscale (P = 0.006), and the mJOA leg subscale (P =
      0.004). There was no relation between depression scores and the Cooper arm
      subscale, Harsh sphincter scale, mJOA sensory subscale, or mJOA bladder subscale.
      Similar patterns were seen in the relations between myelopathy and anxiety.
      CONCLUSION: More than one-third of patients with CSM have a depressed or anxious
      mood. In patients with CSM, depression and anxiety scores are strongly associated
      with decreased mobility, inconsistently associated with arm dysfunction, and not
      associated with sensory deficits or sphincter dysfunction, suggesting that
      ambulatory dysfunction may cause or exacerbate the symptoms of depression and
      anxiety in patients with CSM.

PMID- 16094161
TI  - The anteroinferior cerebellar artery embedded in the subarcuate fossa: a rare
      anomaly and its clinical significance.
AB  - OBJECTIVE: The purpose of this study is to call attention to an anomaly in which
      a segment of the anteroinferior cerebellar artery (AICA) is embedded in the dura
      or bone surrounding the subarcuate fossa, a small depression in the bone
      posterior to the internal acoustic meatus (IAM), through which the subarcuate
      artery enters the bone. This anomaly places the artery at risk in removing the
      posterior wall of the IAM. METHODS: An anomalous AICA having a segment that was
      embedded in the dura covering on the bone surrounding the subarcuate fossa was
      found during a microsurgical dissection course. The senior author (ALR) has
      observed this anomaly in four patients during surgery for acoustic neuromas and
      in three specimens in microsurgery dissection courses. To define the
      microsurgical anatomy of the anomalous artery further, the latex-injected
      specimen was dissected in a stepwise manner using x3 to x40 magnification.
      RESULTS: The anomalous AICA described in this report bifurcated into a rostral
      trunk and a caudal trunk near the facial-vestibulocochlear nerve complex. The
      caudal trunk formed a sharp lateral loop that was embedded in the dura covering
      the subarcuate fossa. The involved trunk continued to supply the suboccipital
      area normally supplied by the posteroinferior cerebellar artery, which was
      hypoplastic. The dura surrounding the anomalous loop was opened, and the adjacent
      bone was removed to free the anomalous loop from the subarcuate fossa so that the
      artery could be displaced medially to remove the posterior wall of the IAM.
      Although it has been reported that the AICA may occasionally be adherent to the
      dura over the subarcuate fossa, this study is the first to demonstrate an AICA
      that is embedded in the dura and bone of the subarcuate fossa. CONCLUSION:
      Mobilizing the AICA loop that is embedded in the subarcuate fossa posterior to
      the IAM places the involved AICA at significant risk in exposing the contents of
      the IAM.

PMID- 16094162
TI  - A quantitative model of tumor-induced angiogenesis in the nude mouse.
AB  - OBJECTIVE: Novel animal models allowing for the quantification of tumor-induced
      angiogenesis and cell migration may offer significant insight into the
      characterization and multidisciplinary treatment of brain tumors. In this study,
      we seek to establish such a model in tumor-bearing brain, allowing for a clear
      demarcation of primary and satellite tumor tissue in conjunction with precise
      quantification of cerebral microvasculature. METHODS: We used green fluorescent
      protein-transfected 9L-gliosarcoma cells stereotactically injected into the brain
      parenchyma of nude mice perfused with tetramethylrhodamine-dextran immediately
      before they were killed. New three-dimensional analytical software developed in
      our laboratory provided a quantitative analysis of laser-scanning confocal
      microscopy images of dextran-labeled cerebral microvessels. RESULTS: Our data
      confirm significant angiogenesis in tumor and brain adjacent to tumor.
      CONCLUSION: Because these highly infiltrative malignant brain tumors
      interdigitate with normal brain parenchyma through finger-like projections at the
      periphery of the solid tumor boundary, therapeutic options targeting tumor blood
      flow--combined with novel three-dimensional imaging to localize and track such
      interventions--may offer new hope for glioma management. To our knowledge, this
      system represents the first animal brain tumor model allowing for the precise
      colocalization and quantification of angiogenesis and tumor cell invasion, which
      may play an important role in the development of future therapy for brain tumors.

PMID- 16094163
TI  - Transplantation of vascular endothelial growth factor-transfected neural stem
      cells into the rat brain provides neuroprotection after transient focal cerebral
      ischemia.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) stimulation and neural stem
      cell (NSC) transplantation have been implicated in the treatment of cerebral
      ischemia because of their crucial roles in neuroprotection, neurogenesis, and
      angiogenesis. However, effective delivery of VEGF or NSCs remains difficult. This
      study attempted to explore whether VEGF121 complementary deoxyribonucleic acid
      could be transferred into the NSCs and, furthermore, whether transplanting these
      VEGF121-transfected NSCs into the rat brain provides sufficient neuroprotection
      after transient focal cerebral ischemia. METHODS: The VEGF121 gene was
      transfected to the NSCs isolated from E14 fetal rat hippocampus. In vitro studies
      revealed that VEGF messenger ribonucleic acid could be consistently expressed in
      NSCs from 1 day to up to 2 weeks. RESULTS: After transplantation of VEGF121
      transfected NSCs into the perifocal area of the ischemic rat brain, we found that
      these cells could survive and migrate in the ischemic region for 12 weeks.
      Furthermore, we observed a significant improvement of the Neurological Severity
      Scale score in the rats transplanted with VEGF121-transfected NSCs in comparison
      to the phosphate-buffered saline-injected or the sham-operated rats (P < 0.05).
      Transplantation of nontransfected NSCs into ischemic rat brain improved the
      Neurological Severity Scale score as well. Of note, the improvement in the
      Neurological Severity Scale score occurred earlier in the VEGF121-transfected NSC
      rats than in the nontransfected NSC rats (range, 2-12 wk versus 8-12 wk),
      suggesting a potent neuroprotection mediated by additional VEGF121 transfection.
      CONCLUSION: We conclude that transplantation of VEGF121-transfected NSCs improved
      ischemic neurological deficiency. This finding provides a novel approach for the
      treatment of cerebral ischemia.

PMID- 16094164
TI  - MitoKATP-channel opener protects against neuronal death in rat venous ischemia.
AB  - OBJECTIVE: Mitochondrial adenosine triphosphate-dependent potassium (mitoKATP)
      channels are present in the brain, and several reports have shown their
      neuroprotective, preconditioning effect against an ischemic insult. The role of
      mitoKATP channels in the penumbra area has not been studied thoroughly. In a
      model of venous ischemia, widespread penumbra-like low flow areas are created,
      which are susceptible to cortical spreading depression. Thus, we studied effects
      of mitoKATP channels on infarct size in this model. METHODS: Male Wistar rats
      were subjected to two-vein occlusion by photochemical thrombosis of two adjacent
      cortical veins combined with KCl-induced cortical spreading depression. The rats
      were assigned to four experimental groups pretreated intraventricularly 15
      minutes before two-vein occlusion with 1) vehicle, 2) the mitoKATP channel opener
      diazoxide (2 mmol/L), 3) diazoxide (2 mmol/L) plus the selective mitoKATP channel
      blocker 5-hydroxydecanoate (5-HD; 100 mmol/L), or 4) 5-HD alone (100 mmol/L).
      Regional cerebral blood flow (laser Doppler scanning) and brain cell swelling
      (impedance) were monitored acutely. Infarct volume was assessed 7 days after
      ischemia. RESULTS: Pretreatment with diazoxide significantly reduced the infarct
      volume from 6.2 +/- 0.7 mm3 to 3.8 +/- 0.4 mm3, whereas regional cerebral blood
      flow in the vicinity of the two veins was comparable in both groups 70 minutes
      after two-vein occlusion. Effects of diazoxide were abolished by 5-HD, whereas 5
      HD alone even increased infarct volume. CONCLUSION: These results suggest that
      the opening of mitoKATP channels plays a major role in brain protection under
      penumbra-like conditions, as shown in this venous occlusion model.

PMID- 16094165
TI  - A novel intravertebral tumor model in rabbits.
AB  - OBJECTIVE: Although the majority of human epidural spinal metastases originate in
      the vertebral body, current animal models of spinal epidural tumors are limited
      to extraosseous tumor placement. We investigated the onset of paraparesis,
      radiographic changes (magnetic resonance imaging [MRI] and computed tomographic
      [CT] scans), and histopathological findings after intraosseous injection of VX2
      carcinoma cells into the lower thoracic vertebrae of rabbits. METHODS: New
      Zealand white rabbits (n = 23) were injected with a 15-mul suspension containing
      300,000 VX2 carcinoma cells in the lowest thoracic vertebral body. Lower
      extremity motor function was assessed daily. For the first 3 animals, MRI scans
      (T2-weighted and T1-weighted +/- gadolinium) were acquired at postoperative day
      (POD) 14 and at the onset of paraparesis. Noncontrast CT scans were obtained on
      POD 7 and at the time of paraparesis. At the onset of paraparesis, the animals
      ware killed and the spines were dissected. After demineralization, hematoxylin
      and eosin cross sections were obtained. RESULTS: Before the onset of paraparesis,
      the CT and MRI scans revealed no gross tumor. At the onset of paraparesis, CT
      scans demonstrated an osteolytic tumor centered at the junction of the left
      pedicle and vertebral body, and MRI scans demonstrated epidural tumor arising
      from the body and compressing the spinal cord. Histopathological examination
      confirmed carcinoma arising from the body and extending into the canal, with
      widespread osteolytic activity. By POD 28, 72% of the animals had become
      paraparetic, and by the termination of the experiment on POD 120, 89% had become
      paraparetic. CONCLUSION: We established a novel intraosseous intravertebral tumor
      model in rabbits and characterized it with respect to onset of paraparesis,
      imaging features, and histopathological findings.

PMID- 16094166
TI  - Reminiscences on stereotactic neurosurgery.
AB  - This report is a straightforward account of the author's personal experience as a
      practicing neurosurgeon, particularly his experience in the surgical treatment of
      Parkinson's disease, before the discovery of the partially successful medical
      treatment using the drug L-dopa. Even today, L-dopa plays a major role in
      alleviating the disabling symptoms of Parkinson's disease. Frank revelations are
      made of events not usually included in the medical literature, or even in public
      newspapers and journals. Furthermore, no attempt was made by the author to hide
      facts or to protect anyone, including the author himself.

PMID- 16094167
TI  - Retracing "Ondine's curse".
AB  - "Ondine's curse" is a term used to denote a rare neurological condition causing
      failure of automatic respiration. The patients are no longer capable of breathing
      spontaneously-they must consciously and voluntarily force themselves to do so.
      Ondine (also known as "Undine"), a mythological figure of European tradition, was
      a water nymph or sprite who could become human only when she fell in love with a
      mortal man. However, if the mortal was unfaithful to her, he was destined to
      forfeit his life. In the 16th century, Paracelsus coined the term "Undine" to
      describe the spirit that inhabited the element of water. Baron de la Motte-Fouque
      wrote the story of Undine in the late 18th century. It has since become a popular
      subject for theater productions. Jean Giraudoux, the French playwright,
      introduced the concept of the loss of automaticity of all functions as the "curse
      of Ondine." The legend was popularized in the form of the fairy tale "The Little
      Mermaid" by Hans Christian Andersen and as an animated motion picture by Walt
      Disney Productions. In this study, we look at the origins of this eponymous term,
      the personalities intertwined with its popularity, and its misrepresentations in
      the medical literature.

PMID- 16094168
TI  - Pioneers in the development of neurological surgery in Auckland, New Zealand:
      Robertson, Wrightson, and Mackenzie.
AB  - OBJECTIVE: To demonstrate the development of neurosurgery in Auckland, New
      Zealand, which has diverse roots and was influenced by geographical,
      socioeconomic, and international forces. METHODS: Historical records were
      examined, and interviews were conducted to determine the factors that shaped the
      development of neurological surgery in Auckland, New Zealand. RESULTS: Sir
      Carrick Robertson, a Scotsman, was one of the more enterprising general surgeons
      in Auckland. As early as the 1920s, he performed and published the results of
      several neurosurgical procedures. Later, Donald Mackenzie, another Auckland
      general surgeon, went abroad to gain neurosurgical experience from his North
      American and British colleagues. He returned and founded the Auckland
      Neurosurgical Department in 1945. David Robertson and Phillip Wrightson later
      joined the department, and they were instrumental in conducting early research on
      shunt systems, head injury, and pituitary tumors. The neurosurgical department
      Mackenzie founded went on to become the largest in New Zealand and presently
      serves metropolitan Auckland as well as both rural areas of New Zealand's North
      Island and many smaller Pacific island nations. CONCLUSION: Neurological surgery
      in Auckland was influenced largely by Great Britain, Australia, and North
      America, as well as by geographical and socioeconomic factors unique to the South
      Pacific. The achievements of these earlier pioneers in neurosurgery highlight
      their tremendous abilities and sheer determination to succeed.

PMID- 16094171
TI  - Letting the family in during a code.

PMID- 16094172
TI  - Demystifying biphasic defibrillation.
AB  - This technology is making defibrillators less likely to injure patients. Here's
      what you need to know.

PMID- 16094174
TI  - Family presence during resuscitation.
AB  - Are policies allowing family into the trauma room humane and necessary--or just
      asking for trouble?

PMID- 16094175
TI  - Meeting the JCAHO patient-safety goals.

PMID- 16094176
TI  - Choosing the best stethoscope.
AB  - Go beyond the bells and whistles to learn how to select this important assessment
      tool.

PMID- 16094177
TI  - Amazing grace.
AB  - What a badly burned child taught me about perseverance.

PMID- 16094178
TI  - Bouncing patients?
AB  - Emergency department capacity issues and diversion status toy with efficient
      patient flow.

PMID- 16094179
TI  - A clarion call for clinical nurse specialists.

PMID- 16094182
TI  - Revealed: 2006 National Patient Safety Goals.
AB  - The Joint Commission reveals 2006 National Patient Safety Goals requirements.

PMID- 16094183
TI  - Navigate through conflict, not around it.
AB  - Conflict can be a learning experience, not a stressful one.

PMID- 16094184
TI  - Get creative with performance improvement plans.
AB  - Initiate a performance improvement plan to facilitate nursing education and
      recruitment.

PMID- 16094186
TI  - Best-practice protocols: evidence-based care for acute myocardial infarction.
AB  - Through its performance improvement service lines, Hackensack University Medical
      Center first reduced, and then eliminated, the occurrence of cardiac-related,
      inadequate "hand-off," defined as delays in getting the right treatment to the
      patient at the right time.

PMID- 16094187
TI  - Learn to speak finance.
AB  - To best prepare for developing budgets, know your volume base. Realize who and
      where your competition is and plan accordingly.

PMID- 16094189
TI  - Keys to nursing research within a community hospital.
AB  - Administrators promote interest in research among all levels of clinical staff.

PMID- 16094190
TI  - Neonatal security: it takes a community.
AB  - A heightened awareness of infant security issues surfaced in the 1990s, driven by
      attempted and successful infant abductions. During that time, many hospitals
      began implementing policies, procedures, and staff training to protect the babies
      in their care. In addition, high-profile hospitals began investing in infant
      security systems as a technological aid to bolster security.

PMID- 16094191
TI  - Go wireless, get to-the-minute data tracking.
AB  - Nurses in a large Midwestern medical center use PDAs to track their patients'
      infusion therapy data in real time.

PMID- 16094195
TI  - Venture toward the less obvious.

PMID- 16094196
TI  - Damage caps and malpractice premiums.

PMID- 16094198
TI  - Evaluation and treatment of pediatric ADHD.

PMID- 16094200
TI  - Venous thromboembolism: a guide to prevention and treatment.

PMID- 16094202
TI  - Cancer screening: principles and controversies.

PMID- 16094203
TI  - West Nile Virus.

PMID- 16094212
TI  - Patient trust crucial for diagnosing gonococcal arthritis.

PMID- 16094213
TI  - Accurate diagnosis of postmenopausal bleeding.

PMID- 16094217
TI  - Evaluation of a quadrivalent measles, mumps, rubella and varicella vaccine in
      healthy children.
AB  - BACKGROUND: A quadrivalent measles, mumps, rubella and varicella vaccine would
      facilitate universal immunization against all 4 diseases, improve compliance and
      immunization rates and decrease the number of injections given to children and
      visits to physicians' offices. OBJECTIVES: To evaluate 1- and 2-dose regimens of
      a combined measles, mumps, rubella and varicella vaccine (ProQuad, referred to as
      MMRV) manufactured with a varicella component of increased potency. METHODS: In
      this partially blind, multicenter study, 480 healthy 12- to 23-month-old children
      were randomized to receive either MMRV and placebo or M-M-RII and VARIVAX.
      Injections were given concomitantly at separate sites. Subjects randomized to
      receive MMRV and placebo received a second dose of MMRV 90 days later. Subjects
      were followed for 42 days after each vaccination for adverse experiences.
      Immunogenicity was evaluated 6 weeks after each vaccination. RESULTS: Measles
      like rash and fever during days 5-12 were more common after the first dose of
      MMRV (rash, 5.9%; fever, 27.7%) than after M-M-RII and VARIVAX (rash, 1.9%;
      fever, 18.7%). The incidence of other adverse events were similar between groups.
      Response rates were >90% to all vaccine components in both groups. Geometric mean
      titers to measles and mumps were significantly higher after 1 dose of MMRV than
      after administration of M-M-RII and VARIVAX. The second dose of MMRV elicited
      slight to moderate increases in measles, mumps and rubella antibody titers and a
      substantial increase in varicella antibody titer (from 13.0 to 588.1 glycoprotein
      antigen-based enzyme-linked immunosorbent assay units/mL). CONCLUSION: A 1- or 2
      dose regimen of MMRV is generally well-tolerated when administered to 12- to 23
      month-old children and has a safety and immunogenicity profile similar to that of
      M-M-RII and VARIVAX administered concomitantly.

PMID- 16094218
TI  - Dose-response study of a quadrivalent measles, mumps, rubella and varicella
      vaccine in healthy children.
AB  - BACKGROUND: A combined measles, mumps, rubella and varicella (MMRV) vaccine would
      facilitate universal immunization against 4 diseases by decreasing the number of
      injections and thus enhancing compliance and coverage rates. If a second dose of
      varicella vaccine were to be recommended, MMRV could be used to administer a
      routine second dose of M-M-RII with the added advantage of boosting varicella
      zoster virus (VZV) antibody titers. METHODS: Subjects 12-23 months of age
      received a single injection of 1 of 3 lots of an MMRV vaccine (ProQuad)
      containing high, middle or low VZV potency, or VARIVAX given concomitantly with M
      M-RII. Recipients of MMRV received a second injection of MMRV approximately 90
      days later. RESULTS: We enrolled 1559 subjects in the study. Antibody response
      rates to VZV 6 weeks after 1 injection of high potency MMRV (88.6%) or 2
      injections of MMRV of any varicella potency (99.7-100%) were similar to the
      response rates after concomitant administration of M-M-RII and VARIVAX (93.1%).
      The second injection of MMRV boosted VZV antibody titers. Antibody responses to
      measles, mumps and rubella were >or=98%, similar to the control, after 1 or 2
      injections of MMRV. MMRV was generally well-tolerated during the 42 days after
      vaccination. CONCLUSIONS: One injection of high potency MMRV resulted in antibody
      responses to the 4 vaccine components equivalent to those found after concomitant
      administration of M-M-RII and VARIVAX. A second injection of MMRV resulted in a
      significant boost in VZV antibody. This boost may translate into enhanced
      immunogenicity against varicella, which is known to correlate with increased
      protection.

PMID- 16094219
TI  - Chlorhexidine-impregnated dressing for prevention of colonization of central
      venous catheters in infants and children: a randomized controlled study.
AB  - BACKGROUND: Infections of short term, nontunneled, intravascular catheters are
      often caused by migration of organisms from the insertion site. The aim of this
      study was to evaluate the effectiveness and safety of a chlorhexidine gluconate
      impregnated dressing for the reduction of central venous catheter (CVC)
      colonization and CVC-associated bloodstream infections in infants and children
      after cardiac surgery. METHODS: This prospective, randomized, controlled study
      was conducted in the pediatric cardiac intensive care unit of a tertiary care
      pediatric medical center. Patients 0-18 years of age who were admitted to the
      pediatric cardiac intensive care unit during a 14-month period and required a CVC
      for >48 hours were randomized to receive a transparent polyurethane insertion
      site dressing (control group) or a chlorhexidine gluconate-impregnated sponge
      (Biopatch) dressing covered by a transparent polyurethane dressing (study group).
      The main outcome measures were rates of bacterial colonization, rates of CVC
      associated bloodstream infections and adverse events. RESULTS: Seventy-one
      patients were randomized to the control group and 74 to the study group. There
      were no significant between group differences in age, sex, Pediatric Risk of
      Mortality score or cardiac severity score. CVC colonization occurred in 21
      control patients (29%) and 11 (14.8%) study patients (P = 0.0446; relative risk,
      0.6166; 95% confidence interval, 0.3716-1.023). Bloodstream infection occurred in
      3 patients (4.2%) in the control group and 4 patients (5.4%) in the study group.
      Local redness was noted in 1 control patient and 4 study group patients.
      CONCLUSIONS: The chlorhexidine gluconate-impregnated sponge is safe and
      significantly reduces the rates of CVC colonization in infants and children after
      cardiac surgery.

PMID- 16094220
TI  - Antibodies to Plasmodium falciparum antigens vary by age and antigen in children
      in a malaria-holoendemic area of Kenya.
AB  - BACKGROUND: Antibodies are important in protection against infection and disease
      caused by Plasmodium falciparum, but the frequencies of antibodies to multiple P.
      falciparum antigens in children are not well-characterized. METHODS: IgG and IgM
      antibodies to the vaccine candidate antigens circumsporozoite protein,
      thrombospondin-related adhesive protein, liver stage antigen-1, apical membrane
      antigen-1, erythrocyte-binding antigen-175 and merozoite surface protein-1 were
      measured by enzyme-linked immunosorbent assay in 110 children 0-50 months of age
      in a malaria holoendemic area of Kenya. RESULTS: A similar pattern was seen for
      IgG antibodies to circumsporozoite protein, thrombospondin-related adhesive
      protein, apical membrane antigen-1 and erythrocyte-binding antigen-175: high
      frequencies (70-90%) in children 0-4 months of age; a decrease in children 5-20
      months of age (35-71%); and progressive increases in children 21-36 and 37-50
      months of age (53-80% and 60-100%, respectively). In contrast, IgG antibodies to
      liver stage antigen-1 were infrequent in children 0-4 months of age (5%) and
      increased with age to 64%, and IgG antibody frequencies to merozoite surface
      protein-1 were similar across age groups (26-52%). IgG antibodies to all antigens
      were predominantly of the IgG1 and IgG3 subclasses. Frequencies of IgM antibodies
      to all antigens were low in children 0-4 months of age (0-15%) and increased with
      age (24-56% in the oldest children). CONCLUSION: In children in a malaria
      holoendemic area, IgM antibody to all P. falciparum antigens is infrequent in the
      first 4 months of life but increases with age and increased exposure. The pattern
      of age-related IgG response frequencies to P. falciparum antigens varies
      significantly by antigen.

PMID- 16094221
TI  - Recurrent culture-confirmed tuberculosis in human immunodeficiency virus-infected
      children.
AB  - INTRODUCTION: Recurrent tuberculosis (TB) is more common among human
      immunodeficiency virus (HIV)-infected than HIV-uninfected adults. There are
      limited data regarding recurrence of TB in children. OBJECTIVE: To determine the
      occurrence of recurrent TB in HIV-infected children with culture-confirmed
      tuberculosis. METHODS: HIV-infected children with culture-confirmed TB,
      identified from 1992 to 2000, were followed until February 2004 for further
      confirmed TB episodes 6 months or more after completion of previous
      antituberculosis therapy. Clinical data and results of special investigations
      were recorded. Restriction fragment length polymorphism (RFLP) analysis of
      Mycobacterium tuberculosis isolates was done when possible. RESULTS: Of 87
      children, 9 had a second episode; 2 of these had a third episode of confirmed TB.
      Adherence to treatment was good in 8; 2 experienced hepatotoxicity, and regimens
      were changed. Chest radiographs were normal in only 2 children after first
      treatment completion. Bacteriologic cure was documented in 7 episodes before
      recurrence. RFLP analysis showed 3 children infected with the same strain
      (relapse) and 1 child with a different strain between episodes 1 and 3
      (reinfection). Two further cases had reinfection based on epidemiologic data and
      drug susceptibility test results. Full comparison of strains by RFLP was not
      possible because of the unavailability of isolates of the first episode in 5
      cases. CONCLUSION: Recurrent TB in HIV-infected children is common in a high
      burden TB setting. Both relapse and reinfection occur.

PMID- 16094222
TI  - Contribution of a broad range polymerase chain reaction to the diagnosis of
      osteoarticular infections caused by Kingella kingae: description of twenty-four
      recent pediatric diagnoses.
AB  - BACKGROUND: Microbiologic diagnosis of septic arthritis and osteomyelitis in
      children is hindered by the less than optimal yield of blood and osteoarticular
      fluid cultures. PATIENTS AND METHODS: All patients admitted to a pediatric unit
      for osteoarticular infections (OAI) between January 2001 and February 2004 were
      enrolled in this prospective study. Osteoarticular fluid and biopsy samples that
      were negative by conventional culture were tested by polymerase chain reaction
      (PCR) with universal 16S ribosomal DNA primers. RESULTS: We enrolled 171
      children. Culture was positive in 64 cases (37.4%), yielding Kingella kingae in 9
      cases. The 107 culture-negative specimens were tested by 16S ribosomal DNA PCR.
      Fifteen samples (14%) were positive, all for Kingella DNA sequences. K. kingae
      was the second cause of OAI in this population (30.4%), after Staphylococcus
      aureus (38%). Patients with Kingella infection diagnosed by culture (9 cases) did
      not differ from those diagnosed by PCR (15 cases) in terms of their clinical
      characteristics (including prior antibiotic therapy). The characteristics of the
      24 children with arthritis (n = 17) or osteomyelitis (n = 7) were similar to
      those reported elsewhere. Fever (>38 degrees C) and symptom onset shortly before
      hospitalization (median, 4.5 days) were significantly associated with arthritis.
      CONCLUSION: Use of molecular diagnostic methods increases the identification of
      K. kingae in osteoarticular infections.

PMID- 16094223
TI  - Effectiveness of measles vaccination after household exposure during a measles
      outbreak: a household contact study in Coburg, Bavaria.
AB  - BACKGROUND: A measles outbreak was recently observed in Coburg, Bavaria, in a
      population with vaccination rates of 76.5% in 5- to 6-year-old children in the
      years preceding the outbreak. Only a small proportion of children had received 2
      vaccinations against measles. Vaccine effectiveness is estimated in a household
      contact study and also by a screening method. METHODS: A household contact study
      was conducted in families with at least 1 measles case by standardized computer
      assisted telephone interviews to assess secondary attack rate and to estimate
      vaccine effectiveness. Vaccine effectiveness was also estimated with Farrington's
      screening method with information from school entry examinations and from
      questionnaires of confirmed measles cases in the Coburg outbreak. RESULTS: Thirty
      eight children were primary cases. Of their contacts, 20 children were included
      in the study as secondary cases (1 vaccinated), and 23 children were contacts who
      did not develop measles (12 vaccinated once and 4 vaccinated twice), resulting in
      a vaccine effectiveness of 90% (95% confidence interval, 35-97%) for one vaccine
      dose. The proportion of the population vaccinated reached 81.5% during the
      outbreak and the proportion of the cases vaccinated was 10.9%, resulting in a
      vaccine effectiveness estimated using the screening method of 97.2% (95%
      confidence interval, 95.7-98.3%). CONCLUSIONS: With the use of 2 approaches to
      estimate the effectiveness of measles vaccination, a consistently high vaccine
      effectiveness of 90% or above was shown during a measles outbreak in Western
      Europe.

PMID- 16094224
TI  - Epidemiology of cat-scratch disease hospitalizations among children in the United
      States.
AB  - BACKGROUND: Cat-scratch disease (CSD), caused by infection with Bartonella
      henselae, affects both children and adults but is principally a pediatric
      disease. Typical CSD is generally benign and self-limited and is characterized by
      regional lymphadenopathy with fever. Infections can, however, be accompanied by
      focal or diffuse inflammatory responses (atypical CSD) involving neurologic,
      organ (liver/spleen), lymphatic or skeletal systems. METHODS: Pediatric
      hospitalizations with CSD listed as a diagnosis were examined using the Kids'
      Inpatient Database for the year 2000. National estimates of CSD-associated
      hospitalizations, hospitalization rates and various hospitalization statistics
      were examined for patients younger than 18 years of age. RESULTS: During 2000, an
      estimated 437 (SE 43) pediatric hospitalizations associated with CSD occurred
      among children younger than 18 years of age in the United States. The national
      CSD-associated hospitalization rate was 0.60/100,000 children younger than 18
      years of age (95% confidence interval, 0.49-0.72) and 0.86/100,000 children
      younger than 5 years of age (95% CI 0.64-1.07). Accompanying diagnoses included
      neurologic complications (12%), organ (liver/spleen) involvement (7%) and "other"
      (5%). Atypical CSD accounted for approximately 24% of the CSD-associated
      hospitalizations. The median charge for a CSD-associated hospitalization was 6140
      dollars with total annual hospital charges of approximately 3.5 million dollars
      among children in the United States. CONCLUSIONS: The CSD-associated
      hospitalization rate among children during 2000 appeared similar to those
      estimated for the 1980s in the United States, despite significant increases in
      cat ownership in the intervening time. Early serologic and molecular testing for
      CSD in children is suggested to minimize unnecessary interventions and promote
      optimally effective care when supportive measures are required.

PMID- 16094225
TI  - Diagnostic utility of Borrelia burgdorferi cerebrospinal fluid polymerase chain
      reaction in children with Lyme meningitis.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) laboratory tests are frequently collected
      to help differentiate Lyme meningitis from other causes of aseptic meningitis.
      Previous studies using Lyme CSF polymerase chain reaction (PCR) have yielded
      varied results (sensitivity between 10 and 90%). No studies have specifically
      examined the diagnostic utility of Lyme CSF-PCR in North American children with
      Lyme meningitis. METHODS: Retrospective chart review of children presenting to a
      children's hospital in a Lyme-endemic region between October 1999 and September
      2004. Patients were included if they had both Lyme serology and Lyme CSF-PCR
      performed during the same hospital encounter and had documented meningitis.
      Patients were considered to have Lyme meningitis if they had meningitis and met
      CDC criteria for Lyme disease. The Lyme CSF-PCR assay amplified a Borrelia
      burgdorferi DNA flagellin gene sequence. RESULTS: Of 108 patients with meningitis
      who qualified for the study, 20 patients met criteria for Lyme meningitis and 88
      were classified as aseptic meningitis. Positive Lyme CSF-PCR was found in 1
      patient (1 of 20, 5%) with Lyme meningitis and one patient classified as aseptic
      meningitis (1 of 88, 1%). Lyme CSF-PCR had a sensitivity of 5% and a specificity
      of 99%. The only Lyme meningitis patient with positive Lyme CSF-PCR had the
      highest CSF white blood cell count and CSF protein values compared with the other
      Lyme meningitis patients. CONCLUSIONS: This is the first study to evaluate Lyme
      CSF-PCR exclusively in North American children. This commercially available
      laboratory test is not generally helpful for identifying Lyme meningitis because
      of its low sensitivity.

PMID- 16094226
TI  - New antigens for serologic diagnosis of neuroborreliosis in children.
AB  - OBJECTIVE: To evaluate serology with novel Borrelia-specific protein or peptide
      antigens in the laboratory diagnosis of neuroborreliosis (NB) in children.
      METHODS: The performance of enzyme-linked immunosorbent assays with several
      recombinant borrelial protein antigens and invariable region 6 synthetic peptide
      antigen and of a commercial enzyme-linked immunosorbent assay with the flagella
      antigen were evaluated in the serodiagnosis and follow-up of children with
      clinical suspicion of NB. Serum samples were obtained from 20 children with
      neurologic symptoms indicative of NB. The patients were retrospectively divided
      into 2 groups based on the laboratory tests at presentation indicating definite
      (n = 7) or probable (n = 13) NB. RESULTS: In addition to cerebrospinal fluid
      (CSF) lymphocytic pleocytosis and CSF antiflagella antibodies, all 7 patients
      with definite NB had serum IgG antibodies to at least 2 of the 3 novel antigens
      at presentation. The 13 patients with probable NB had variable laboratory
      findings: CSF pleocytosis (n = 7), CSF antiflagella IgM antibodies (n = 4), serum
      antiflagella IgM and/or IgG antibodies (n = 10). Of these 13 patients, 7 had
      serum IgG antibodies to 2 of the 3 novel antigens at presentation. During long
      term follow-up, serum anti-invariable region 6 antibodies disappeared.
      CONCLUSIONS: The present study suggests that assessment of serum antibodies to a
      panel of Borrelia-specific antigens could improve the laboratory diagnosis of NB
      at presentation.

PMID- 16094227
TI  - Nosocomial bacteremia in neonates related to poor standards of care.
AB  - BACKGROUND: In developing countries, intravenous liquids are mixed and
      administered by nurses, sometimes under suboptimal infection control conditions.
      We hypothesized that outbreaks of infusate-associated neonatal bacteremias are
      common, and we evaluated whether they can be detected by vigilant microbiologic
      surveillance of infusates. METHODS: We studied intravenous infusates administered
      to neonates in a Mexican hospital where mixtures of infusates were prepared in
      hospital wards. The study was performed in 3 stages: stage 1, initial culturing
      of in-use infusates under basal conditions; stage 2, prospective culturing during
      a cluster of clinical sepsis; and stage 3, final culturing once the outbreak was
      controlled. RESULTS: In stage 1, 68 infusates were sterile, and 1 was
      contaminated with Staphylococcus aureus (1.45%), from 23 patients. In stage 2, of
      182 infusates from 39 patients, 51 infusates (28%) were contaminated with Gram
      negative rods. On the first day of stage 2, 11 of 15 infusates were contaminated
      with the same strain of Klebsiella pneumoniae, which continued to appear for 26
      days. Another 4 strains of Gram-negative rods were also isolated during stage 2.
      The association between contaminated infusate and death was significant (odds
      ratio, 9.4; 95% confidence interval, 2-44.3; P < 0.001). Mixtures made by nurses
      were more likely contaminated than commercial preparations (odds ratio, 3.1; 95%
      confidence interval, 1.1-8.5; P = 0.037). In stage 3, there were 42 sterile
      infusates from 22 patients. CONCLUSIONS: Our study suggests that poor standards
      of care common in hospitals from developing countries sometimes result in
      outbreaks of sepsis and death for newborn patients.

PMID- 16094228
TI  - Leukocyte aggregation-related pseudoleukopenia in pediatrics: a sporadic event or
      a systematic error?
AB  - OBJECTIVE: To determine whether electronic counter-related pseudoleukopenia is a
      rare phenomenon or a systematic underestimation in children with acute
      infection/inflammation. METHODS: We have used a simple slide test and image
      analysis to reveal the number of white blood cells and their degree of
      aggregation. The number of leukocytes counted by an electronic cell analyzer was
      divided by the number of cells counted on the slides creating an electronic cell
      to-slide leukocyte count ratio. RESULTS: A significant (P < 0.0005) negative (r =
      -0.314) correlation between the above mentioned ratios and the percent of
      aggregated leukocytes in the peripheral blood was found in a group of 239
      children with various acute infections. Thus elevated leukocyte aggregation is
      associated with a relatively lower electronic analyzer cell count. CONCLUSIONS:
      The appearance of aggregated leukocytes in the peripheral blood during acute
      infections might be associated with pseudoleukopenia. This phenomenon has been
      extensively described in the adult population and seems to exist in children as
      well.

PMID- 16094229
TI  - Pertussis in adolescents: increasing incidence brings attention to the need for
      booster immunization of adolescents.
AB  - As a result of waning immunity and improved awareness, the reported incidence of
      pertussis is increasing among adolescents in the United States. Symptoms of
      pertussis are often mild and difficult to diagnose in adolescents, but these
      individuals can transmit the infection to schoolmates and family members,
      including high risk infants. Improvements in diagnosis and prevention of
      pertussis in adolescents are needed.

PMID- 16094230
TI  - Impact of conjugate pneumococcal vaccines.

PMID- 16094231
TI  - Epidemiologic study of conjunctivitis-otitis syndrome.
AB  - We conducted a prospective cross-sectional epidemiologic study of conjunctivitis
      otitis syndrome during two 3-week periods of consecutive winters. A
      representative sample of 184 pediatricians and ear, nose and throat specialists
      in the Paris area recruited 2901 children from 6 to 36 months of age presenting
      with acute otitis media, of whom 465 (16%) also had purulent conjunctivitis. In
      sampled children, the culture of the conjunctival exudate yielded bacterial
      pathogens in 419 patients: Haemophilus influenzae, 371 (89%); Streptococcus
      pneumoniae, 72 (17%); and Branhamella catarrhalis, 23 (5%). Pulsed field gel
      electrophoresis analysis of paired H. influenzae isolates from the conjunctival
      exudate and middle ear fluid of 21 patients showed identical strains in each
      patient.

PMID- 16094232
TI  - Clinical presentation and characteristics of pharyngeal adenovirus infections.
AB  - We describe the clinical characteristics of 209 children younger than 15 years of
      age with positive pharyngeal cultures for adenovirus. The mean age of the
      children was 37 +/- 33 months, and the mean peak temperature was 39.2 +/- 0.76
      degrees C. On physical examination, tonsillitis was found for 88% of children;
      52% of them had exudative tonsillitis. Forty-eight percent of the patients who
      had a white blood cell count performed had >15,000 leukocytes per mm, and 25% had
      >20,000 leukocytes per mm. C-reactive protein concentrations were >7 mg/dL for
      22.5% of the patients. Adenovirus pharyngeal infections in young children mimic
      severe bacterial infections.

PMID- 16094233
TI  - Respiratory syncytial virus and human metapneumovirus in children with acute
      respiratory infections in Yemen.
AB  - A survey of 604 Yemeni children younger than 2 years with acute respiratory
      infections identified respiratory syncytial virus (RSV) in 244 (40%), human
      metapneumovirus (HMPV) in 41 (7%) and RSV/HMPV coinfection in 25 (4%) children.
      RSV infections occurred in younger children and were associated with more severe
      hypoxia than observed with HMPV. Both viruses are important causes of severe
      acute respiratory infection in Yemen.

PMID- 16094234
TI  - Risk factors for mortality in children with candidemia.
AB  - We performed a retrospective cohort study of hospitalized children with positive
      blood cultures for Candida species. Independent risk factors for mortality by
      multivariable analysis were location in the pediatric intensive care unit at the
      time of infection (hazard ratio, 6.3; 95% confidence interval, 1.6-24.3) and the
      presence of an arterial catheter (hazard ratio, 2.4; 95% confidence interval, 1.1
      5.8). Our findings help identify a group of pediatric patients that should be
      targeted for future interventions to prevent and treat candidemia.

PMID- 16094235
TI  - Frequent Haemophilus influenzae type B colonization in rural Thailand.
AB  - In Asia, there is uncertainty regarding whether the burden of Haemophilus
      influenzae type b (Hib) disease is great enough to warrant vaccination. In this
      nasopharyngeal carriage study in rural Thailand, 7% of children younger than 5
      years of age carried Hib, a prevalence similar to that found in countries with
      high rates of Hib disease before vaccine introduction.

PMID- 16094236
TI  - Acanthosis nigricans as an adverse effect of highly active antiretroviral therapy
      in an adolescent girl with human immunodeficiency virus infection.
AB  - We report an 11-year-old girl with acanthosis nigricans that appeared after 4
      years of treatment with didanosine, stavudine and amprenavir. Laboratory studies
      showed hyperglycemia, hyperinsulinemia and hypertriglyceridemia. Withdrawal of
      amprenavir resulted in disappearance of acanthosis nigricans and improvement of
      metabolic abnormalities.

PMID- 16094237
TI  - Adult-type pulmonary tuberculosis in children 10-14 years of age.
AB  - We report 8 children (10-14 years of age) who were diagnosed with tuberculosis at
      their local primary health care clinic from July to September 2004, after routine
      sputum testing was extended to all children older than 10 years of age with
      suspected tuberculosis. This case series emphasizes that older children develop
      adult-type cavitating disease, which can be diagnosed by sputum smear microscopy,
      in contrast to younger children for whom smear microscopy has very little
      diagnostic value.

PMID- 16094238
TI  - Congenital Candida glabrata infection without specific nodules on the placenta
      and umbilical cord.
AB  - Two extremely premature infants died as a result of congenital Candida glabrata
      infection, and their placentas and umbilical cords were free of macroscopic
      Candida nodules. Because non-Candida albicans Candida infections are less likely
      to produce necrotic foci, we should not exclude Candida infections in the absence
      of macroscopic nodules on the placenta and umbilical cord.

PMID- 16094239
TI  - Lung nodules in a thirteen-year-old male youth.

PMID- 16094240
TI  - Genotyping for guiding drug choice in human immunodeficiency virus-infected
      children failing multiple antiretroviral treatment regimens.

PMID- 16094241
TI  - Broviac catheter-related candidemia.

PMID- 16094242
TI  - Prevalence of asymptomatic carriers and cases of tinea capitis in five to six
      year-old preschool children from Augsburg, Germany: results from the MIRIAM
      study.

PMID- 16094243
TI  - Neisseria meningitidis subdural empyema in a young infant.

PMID- 16094244
TI  - Enhanced culture detection of Citrobacter koseri from cerebrospinal fluid in
      BacTec.

PMID- 16094245
TI  - The Third Annual Pharmacogenetics in Psychiatry Meeting, 2004.

PMID- 16094246
TI  - II. Serotonin receptor gene polymorphisms and their association with tardive
      dyskinesia among schizophrenia patients from North India.

PMID- 16094247
TI  - The short/long polymorphism in the serotonin transporter gene promoter is not
      associated with panic disorder in a Scandinavian sample.

PMID- 16094248
TI  - Melanocortin-4 receptor molecular scanning and pro-opiomelanocortin R236G variant
      screening in binge eating disorder.

PMID- 16094249
TI  - Further tests of the association between schizophrenia and single nucleotide
      polymorphism markers at the catechol-O-methyltransferase locus in an Askenazi
      Jewish population using microsatellite markers.
AB  - Association studies are now primarily being conducted with single nucleotide
      polymorphisms because they are present everywhere in the genome and can be
      genotyped in "high throughput" formats. Microsatellite markers have a higher
      degree of polymorphism than single nucleotide polymorphisms and have been widely
      used in both linkage and association studies of disease. Polymorphic
      microsatellite markers with several alleles can readily detect linkage
      disequilibrium but at any given locus there may be differences between single
      nucleotide polymorphisms and microsatellites in their power to detect linkage
      disequilibrium because of the evolutionary history of the locus, especially the
      rate at which both the single nucleotide polymorphisms and microsatellite
      polymorphisms have mutated and the number of disease mutations and their history.
      In the current study, we examined the efficiency of microsatellite markers in
      association analysis by looking at all existent microsatellite markers in the
      catechol-O-methyltransferase gene region and by genotyping these microsatellites
      in a large cohort of schizophrenia patients and healthy controls, a subset of a
      sample where catechol-O-methyltransferase and schizophrenia were found to be
      associated. We also estimated the levels of linkage disequilibrium between these
      microsatellites and the previously reported single nucleotide polymorphisms
      (within the catechol-O-methyltransferase gene) found to be associated with
      schizophrenia. A modest allelic association of P=0.041 was found between
      schizophrenia and the microsatellite marker D22S944, which was not significant,
      however, when corrected for all microsatellites tested. Nevertheless, significant
      linkage disequilibrium was found between this marker and the three single
      nucleotide polymorphisms within the catechol-O-methyltransferase gene that
      displayed association with the disease in the previously published research on
      this sample. Significant linkage disequilibrium was also observed between
      microsatellites up to approximately 300 kb distant from those single nucleotide
      polymorphisms. Although significant, the extent of linkage disequilibrium in
      terms of r2 was small (in the order of 0.01).

PMID- 16094250
TI  - Association study of dopamine D2 and D3 receptor gene polymorphisms with cocaine
      dependence.
AB  - Genetic factors play a role in the vulnerability to cocaine dependence. The
      reinforcing properties of cocaine are related to the dopaminergic system, and, in
      particular, the dopamine receptors have been linked to the reward mechanisms. The
      present study examines the role of the variants TaqI A of the dopamine D2
      receptor gene and BalI of the dopamine D3 receptor gene in a Brazilian sample
      consisting of 730 cocaine dependents and 782 healthy controls. The studied
      polymorphisms did not show any difference in allelic frequencies or genotypic
      distribution between the groups. Our data do not support a role for the dopamine
      D2 receptor gene TaqI A and dopamine D3 receptor gene BalI gene polymorphisms in
      the susceptibility to cocaine dependence in a Brazilian sample.

PMID- 16094251
TI  - A family genetic study of clinical subtypes of obsessive-compulsive disorder.
AB  - OBJECTIVE: The results of various family studies of obsessive-compulsive disorder
      have varied widely, possibly because of heterogeneity in the obsessive-compulsive
      disorder phenotype. The current study was conducted to determine familiality of
      checker and washer subtypes of obsessive-compulsive disorder compared with normal
      controls. METHODS: In this study, all available first-degree relatives of 25
      checker, 34 washer and 40 psychiatrically normal control probands were
      interviewed directly, using structured interviews. RESULTS: The morbid risk of
      syndromal and subsyndromal obsessive-compulsive disorder was significantly
      greater among the relatives of checker probands (19.4%) than in the relatives of
      washer (8.7%) or control probands (5.4%), while the morbid risk for the relatives
      of washer and control probands was not significantly different. In all, 67% of
      the checker relatives with syndromal and subsyndromal obsessive-compulsive
      disorder were checkers, while 54% of the washer relatives with syndromal and
      subsyndromal obsessive-compulsive disorder were washers. CONCLUSIONS: Our study
      provides preliminary evidence of familiality of the checker subtype of obsessive
      compulsive disorder. Future studies using patients subtyped on the basis of
      symptom dimensions, in larger obsessive-compulsive disorder samples, are needed,
      to further validate the genetic basis of obsessive-compulsive disorder.

PMID- 16094252
TI  - A new method of linkage analysis using LOD scores for quantitative traits
      supports linkage of monoamine oxidase activity to D17S250 in the Collaborative
      Study on the Genetics of Alcoholism pedigrees.
AB  - OBJECTIVE: Although LOD score methods have been applied to diseases with complex
      modes of inheritance, linkage analysis of quantitative traits has tended to rely
      on non-parametric methods based on regression or variance components analysis.
      Here, we describe a new method for LOD score analysis of quantitative traits
      which does not require specification of a mode of inheritance. METHODS: The
      technique is derived from the MFLINK method for dichotomous traits. A range of
      plausible transmission models is constructed, constrained to yield the correct
      population mean and variance for the trait but differing with respect to the
      contribution to the variance due to the locus under consideration. Maximized LOD
      scores under homogeneity and admixture are calculated, as is a model-free LOD
      score which compares the maximized likelihoods under admixture assuming linkage
      and no linkage. These LOD scores have known asymptotic distributions and hence
      can be used to provide a statistical test for linkage. The method has been
      implemented in a program called QMFLINK. It was applied to data sets simulated
      using a variety of transmission models and to a measure of monoamine oxidase
      activity in 105 pedigrees from the Collaborative Study on the Genetics of
      Alcoholism. RESULTS: With the simulated data, the results showed that the new
      method could detect linkage well if the true allele frequency for the trait was
      close to that specified. However, it performed poorly on models in which the true
      allele frequency was much rarer. For the Collaborative Study on the Genetics of
      Alcoholism data set only a modest overlap was observed between the results
      obtained from the new method and those obtained when the same data were analysed
      previously using regression and variance components analysis. Of interest is that
      D17S250 produced a maximized LOD score under homogeneity and admixture of 2.6 but
      did not indicate linkage using the previous methods. However, this region did
      produce evidence for linkage in a separate data set, suggesting that QMFLINK may
      have been able to detect a true linkage which was not picked up by the other
      methods. CONCLUSION: The application of model-free LOD score analysis to
      quantitative traits is novel and deserves further evaluation of its merits and
      disadvantages relative to other methods.

PMID- 16094253
TI  - The monoamine oxidase A gene may influence the means used in suicide attempts.
AB  - OBJECTIVE: Compelling evidence suggests that serotonin system dysfunction is
      associated with certain behavioral disorders, including suicidal behavior and
      impulsive aggression. A functional polymorphism in the promoter region of the
      monoamine oxidase A gene (uVNTR) was recently identified and the presence of the
      2-3 alleles was found to be associated with a higher level of transcription,
      central nervous system serotonergic responsivity and impulsive aggression. A
      dinucleotide repeat in intron 2 of the gene (monoamine oxidase A-CAn) has been
      described previously, and is in linkage disequilibrium with the variable number
      of tandom repeats (VNTR). The aim of the study was to investigate, in a large
      sample, whether the monoamine oxidase A gene was involved in the susceptibility
      to suicidal behavior. METHODS: We genotyped 738 West European Caucasians, who had
      made suicide attempts, and 222 controls of the same ethnic origin, with no
      history of suicidal behavior. The two variants of the monoamine oxidase A gene
      have been tested. RESULTS: We did not find any association between the two
      monoamine oxidase A gene variants and suicidal behavior. However, the frequency
      of the uVNTR 2-3 alleles was significantly higher in men who had attempted
      suicide by violent means than in men who had used non-violent means. The odds
      ratio for the uVNTR 2-3 alleles versus the uVNTR 1-4 alleles was 2.17 [95%
      confidence interval (1.08-4.35)]. Haplotypes did not allow strengthening the
      effect observed with the uVNTR. CONCLUSION: These results suggest that an excess
      of high-activity monoamine oxidase A gene promoter alleles may be associated with
      traits orienting suicidal behavior towards a violent act.

PMID- 16094254
TI  - No evidence for an association between variants at the proline dehydrogenase
      locus and schizophrenia or bipolar affective disorder.
AB  - The proline dehydrogenase locus must be considered as a positional and functional
      candidate in schizophrenia. It is located in the chromosomal region of the
      velocardiofacial syndrome on 22q11 that is suspected to contain genes relevant to
      schizophrenia, and is involved in the metabolism of neurotransmitters. Positive
      association between single-nucleotide polymorphisms at the proline dehydrogenase
      locus and schizophrenia further supported the role of proline dehydrogenase in
      the development of schizophrenia. In order to replicate these findings, we
      analyzed three single-nucleotide polymorphisms in a sample comprising 299
      schizophrenic patients and 300 controls. In addition, we assessed whether proline
      dehydrogenase also contributes to bipolar affective disorder, because chromosome
      22q11 is also implicated in bipolar affective disorder. We therefore included 300
      patients with bipolar affective disorder. This is the first study on a potential
      involvement of the proline dehydrogenase locus in bipolar affective disorder.
      Neither single marker nor haplotype analysis revealed an association between
      variants at the proline dehydrogenase locus and schizophrenia or bipolar
      affective disorder.

PMID- 16094255
TI  - Identification, characterization, and association analysis of novel genes from
      the bipolar disorder susceptibility locus on chromosome 4q35.
AB  - The cause of bipolar disorder remains unknown, with little knowledge of the
      underlying biological, anatomical, biochemical, or genetic defect. The disorder
      is genetically complex, with an increasing number of loci being implicated
      through genetic linkage studies. We previously identified a bipolar disorder
      susceptibility locus on chromosome 4q35 and refined the interval harboring this
      susceptibility gene to approximately 5 Mb, a size that is amenable to positional
      cloning. Several independent studies have reported the presence of a
      susceptibility gene at this locus. To identify candidate genes for testing for
      association with bipolar disorder, we previously established a transcript map
      that encompasses the candidate interval. We have continued to seek novel genes
      from this region in order to expand this transcript map. Here, we describe the
      further identification and characterization of eight novel genes from the
      chromosome 4q35 bipolar candidate interval. Expression analysis determined that
      six of these novel genes are expressed in the brain, and these genes were
      therefore analyzed for association with bipolar disorder. Single nucleotide
      polymorphisms were identified from the candidate genes and tested for association
      in our case-control cohort. Our data suggest that the six candidate genes
      analyzed can be excluded from involvement in the disorder.

PMID- 16094256
TI  - Fine mapping of the 5p13 locus linked to schizophrenia and schizotypal
      personality disorder in a Puerto Rican family.
AB  - A locus involved in schizophrenia and related disorders in a Puerto Rican family
      has previously been mapped to chromosome 5p. The maximum two-point log of the
      odds (LOD) score of 3.72 was obtained for marker D5S111, and increased to 4.37 by
      multipoint analysis, assuming autosomal dominant inheritance with 90% penetrance.
      Additional genotyping and haplotype analysis placed the novel locus on 5p13.2
      p13.3 within the interval between markers D5S1993 and D5S631. In the current
      study, we saturated the interval between markers D5S1993 and D5S631 with densely
      spaced polymorphic markers, genotyped these markers in the most informative
      branch of the family, and narrowed the critical region to 2.8 Mb. G-protein
      coupled receptor gene [somatostatin and angiotensin-like peptide receptor
      (SALPR)] is one of the candidate genes within the critical interval. Sequence
      analysis of the coding region and the putative promoter of somatostatin and
      angiotensin-like peptide receptor did not reveal functionally significant
      variants in affected family members, although several polymorphisms were
      detected.

PMID- 16094257
TI  - Association analysis of CHMP1.5 genetic variation and bipolar disorder.
AB  - OBJECTIVES: The18p11.2 region surrounding the G-olf gene has been linked in
      several independent studies to bipolar disorder and schizophrenia, yet
      association studies between G-olf genetic variations and bipolar disorder have
      been negative. We hypothesized that the linkage in this region might be due to a
      gene in close physical proximity to G-olf, and we examined variations in the
      CHMP1.5 gene within intron 5 of G-olf for association with bipolar disorder.
      METHODS: Two single-nucleotide polymorphisms, rs1786581 and rs1249624, were
      analyzed for association with bipolar disorder in 402 unrelated bipolar
      individuals and 181 unrelated controls. Genotyping was performed via
      pyrosequencing and restriction fragment length polymorphism analysis; results
      were compared by chi2 contingency analysis. RESULTS: No evidence was found for
      association of either allele at rs1249624 with bipolar disorder (chi2=1.25,
      degrees of freedom=1, P=0.26); however, a trend towards association with the 'T'
      allele at rs1786581 and with the 'T/T' 1786581/1249624 haplotype was observed.
      The chi2 for the haplotype was 7.16, (degrees of freedom=3, P=0.067) and for
      rs1786581 chi2=3.56, degrees of freedom=1, P=0.060; these differences are not
      statistically significant. CONCLUSIONS: Variation in the CHMP1.5 gene does not
      appear to be associated with bipolar disorder. A systematic assessment of genetic
      variation in the region using association studies will be necessary.

PMID- 16094258
TI  - Identification of single-nucleotide polymorphisms in the human N-methyl-D
      aspartate receptor subunit NR2D gene, GRIN2D, and association study with
      schizophrenia.
AB  - OBJECTIVES: The glutamatergic dysfunction is one of the main hypotheses for the
      pathophysiology of schizophrenia. N-methyl-D-aspartate receptors are of major
      interest because phencyclidine, a non-competitive antagonist of N-methyl-D
      aspartate receptors, produces a schizophrenia-like psychosis. Therefore, the
      genes encoding N-methyl-D-aspartate receptor subunits are strong candidates for
      schizophrenia susceptibility genes. We focused on the N-methyl-D-aspartate
      receptor subunit NR2D gene in the case-control study of schizophrenia. METHODS:
      We screened for polymorphisms in exons, exon-intron boundaries and the 5'
      upstream region of GRIN2D by direct sequencing in 32 Japanese patients. Out of
      the total 13 single-nucleotide polymorphisms identified, we genotyped 200-201
      Japanese patients and 219-221 controls for nine common single-nucleotide
      polymorphisms (minor allele frequency over 0.05). RESULTS: None of the nine
      single-nucleotide polymorphisms showed significant differences in genotype and
      allele frequencies between cases and controls. We observed significant
      associations of pairwise haplotypes in three combinations of four single
      nucleotide polymorphisms, INT10SNP-EX13SNP2, EX13SNP2-EX13SNP3 and EX6SNP
      EX13SNP2, with the disease even after the Bonferroni correction (P=1.094 x 10(
      6), Pcorrected=2.297 x 10(-5), P=2.825 x 10(-6), Pcorrected=5.933 x 10(-5) and
      P=2.02 x 10(-4), Pcorrected=4.242 x 10(-3), respectively). The same results were
      also obtained using the false discovery rate (BL) method at the threshold P
      value, 2.908 x 10(-3). CONCLUSIONS: We conclude that the GRIN2D locus is a
      possible genomic region contributing to schizophrenia susceptibility in the
      Japanese population.

PMID- 16094259
TI  - Screening of PIP5K2A promoter region for mutations in bipolar disorder and
      schizophrenia.
AB  - OBJECTIVE: To analyze the promoter region of PIP5K2A, a phosphatidylinositol 4
      phosphate 5-kinase that maps to 10p in a region linked to both bipolar disorder
      and schizophrenia. METHODS: The promoter region was screened by single-strand
      conformation polymorphism analysis and DNA sequencing. Allele frequencies were
      determined in a case-control study. Functional significance of a promoter variant
      was determined by electromobility gel shift assays. RESULTS: Homozygosity for a
      rare putative promoter variant, -1007C-->T, was found in only two patients with
      schizophrenia and in no controls or bipolar patients. The variant forms a 7/8
      base match for the binding site of Oct-1, a member of the POU homeodomain family.
      Electromobility gel shift assays revealed increased binding of a brain-specific
      nuclear protein to the -1007T allele compared with -1007C. CONCLUSION: The data
      suggest that homozygosity for -1007T could be a rare genetic factor in the
      development of schizophrenia.

PMID- 16094260
TI  - Psychiatric symptomatology of Lujan-Fryns syndrome: an X-linked syndrome
      displaying Marfanoid symptoms with autistic features, hyperactivity, shyness and
      schizophreniform symptoms.

PMID- 16094261
TI  - Sacroiliac joint bridging: demographical and anatomical aspects.
AB  - STUDY DESIGN: A descriptive study of the association between sacroiliac joint
      bridging (SIB) and age, gender, laterality, and ethnic origin in a normal
      skeletal population. The effectiveness of radiographs in identifying SIB was also
      evaluated. OBJECTIVES: To characterize the phenomenon of SIB demographically and
      anatomically and to evaluate the validity of diagnosis based on roentgenograms.
      SUMMARY AND BACKGROUND DATA: Although SIB is an important diagnostic parameter in
      many spinal diseases, the type of association between them has never been
      established. Furthermore, the extent of SIB in humans and its relationship to
      demographic parameters await osteological research as radiograph studies hamper
      the results. METHODS: Two thousand eight hundred and forty-five skeleton pelves
      were examined for SIB. Extent and laterality were recorded. Ten pelves (5 with
      SIB and 5 without) were X-rayed and the roentgenograms given to radiologists for
      evaluation. RESULTS: Sacroiliac bridging was present in 12.27% of all males,
      contrasted with only 1.83% of females (P < 0.001). SIB was independent of ethnic
      origin (P = 0.0535) but was age-dependent (r = 0.985; P = 0.0001). Bridging was
      present bilaterally in 38.6% of the individuals and in the superior region in
      72.4%. Diffuse bridging (areas 1-6) was present in only 2.3% of the individuals.
      Radiologic examination was insensitive to diagnosis of SIB. CONCLUSIONS: SIB is a
      common, but predominantly male phenomenon. Its occurrence is age-dependent and
      ethnicity independent. Bridging occurs mainly on the superior aspect of the
      sacroiliac joint. The irregular shape and orientation of sacroiliac joints
      preclude definitely distinguishing normal versus bridged joints from
      roentgenograms. Our findings also negate the belief that bridging/fusion of the
      sacroiliac joint represents the most severe form of osteoarthritis and mandate
      that they be separately recorded and that their significance be determined.

PMID- 16094262
TI  - Acute quadriplegia following closed traction reduction of a cervical facet
      dislocation in the setting of ossification of the posterior longitudinal
      ligament: case report.
AB  - STUDY DESIGN: A case report of acute quadriplegia resulting from closed traction
      reduction of traumatic bilateral cervical facet dislocation in a 54-year-old male
      with concomitant ossification of the posterior longitudinal ligament (OPLL).
      OBJECTIVES: To report an unusual presentation of a spinal cord injury, examine
      the approach to reversal of the injury, and review the treatment and management
      controversies of acute cervical facet dislocations in specific patient subgroups.
      SUMMARY OF BACKGROUND DATA: The treatment of acute cervical facet dislocations is
      an area of ongoing controversy, especially regarding the question of the
      necessity of advanced imaging studies before closed traction reduction of the
      dislocated cervical spine. The safety of an immediate closed, traction reduction
      of the cervical spine in awake, alert, cooperative, and appropriately select
      patients has been reported in several studies. To date, there have been no
      permanent neurologic deficits resulting from awake, closed reduction reported in
      the literature. A case of temporary, acute quadriplegia with complete neurologic
      recovery following successful closed traction reduction of a bilateral cervical
      facet dislocation in the setting of OPLL is presented. METHODS: The clinical
      neurologic examination, radiographic, and advanced imaging studies before and
      after closed, traction reduction of a cervical facet dislocation are evaluated
      and discussed. A review of the literature regarding the treatment of acute
      cervical facet dislocations is presented. RESULTS: Radiographs showed
      approximately 50% subluxation of the fifth on the sixth cervical vertebrae, along
      with computerized tomography revealing extensive discontinuous OPLL. The cervical
      facet dislocation was successfully reduced with an awake, closed traction
      reduction, before magnetic resonance imaging (MRI) evaluation. The patient
      subsequently had acute quadriplegia develop, with the ensuing MRI study
      illustrating severe spinal stenosis at the C5, C6 level as a result of OPLL or a
      large extruded disc herniation. Following an immediate anterior decompression and
      a posterior stabilization procedure, the patient regained full motor and sensory
      function. CONCLUSIONS: This case report highlights the advantages and shows some
      safety concerns regarding immediate, closed traction reduction of cervical facet
      dislocation with real-time neural monitoring in an awake, alert, oriented, and
      appropriately select patient before MRI studies in the setting of preexisting
      central stenosis from OPLL.

PMID- 16094263
TI  - "Primary" benign retroperitoneal and intraspinal dumbbell-shaped cystic teratoma:
      case report.
AB  - STUDY DESIGN: A case of unusual dumbbell-shaped cystic teratoma is presented.
      OBJECTIVES: To investigate and describe an unusual case of retroperitoneal cystic
      teratoma with spinal invasion in an adult. The image findings, minimally invasive
      surgical procedures, and clinical outcome were discussed, and the literature was
      reviewed. SUMMARY OF BACKGROUND DATA: Primary benign cystic teratomas of the
      retroperitoneum are rare. Extension of these lesions into the spinal canal is
      more rare. In this report, by presenting a case of cystic teratoma with such
      extension, the origin of the tumor, and the value of computerized tomography and
      magnetic resonance imaging (MRI) in the preoperative diagnosis and surgical
      approach for the extended lesion are discussed. METHODS: The patient was a 24
      year-old female who had had low back pain with bilateral sciatica for 2 months.
      Preoperative computerized tomography and MRI of the thoracic and lumbar spines
      showed a dumbbell-shaped tumor, with the solid part residing in the right
      retroperitoneum near the neuroforamen of the L2-L3 spines and the cystic part
      extending into the spinal canal. By performing right L2-L4 hemilaminectomies with
      a mini retroperitoneal approach, the tumor was removed en bloc in one stage.
      RESULTS: Diagnosis of cystic teratoma was confirmed by pathologic examination.
      The patient recovered well without any neurologic deficits, and recurrence of
      tumor has not been found for 9 years postoperatively. CONCLUSIONS: Total surgical
      removal of tumor is an ideal treatment for retroperitoneal and intraspinal
      dumbbell-shaped cystic teratoma. MRI displays the precise location, morphology,
      and adjacent structures of the tumor, which provide for better preoperative
      planning and more complete removal of tumor with less neurologic damage.

PMID- 16094264
TI  - Successful reduction for a pediatric chronic atlantoaxial rotatory fixation
      (Grisel syndrome) with long-term halter traction: case report.
AB  - STUDY DESIGN: Clinical case report of atlantoaxial rotatory fixation (AARF) in a
      girl presenting with torticollis and neck pain. OBJECTIVE: To report this rare
      case that was successfully treated with long-term traction and a brace. SUMMARY
      OF BACKGROUND DATA: AARF is a rare kind of subluxation that is a pathologic
      fixation of the atlas on the axis. It is most common in pediatric patients and is
      usually reduced easily with conservative treatments only in the acute stage.
      However, previously reported chronic AARFs have usually been treated with
      operative reductions. Although high success rates have been achieved with
      operative reduction in chronic cases of AARF, even successful operative reduction
      may result in significant neck motion limitation. METHODS: A 9-year-old girl had
      torticollis of more than 3 months duration develop as a result of an upper
      respiratory infection. Dynamic computerized tomography showed consistent fixation
      of the atlantoaxial joint consistent with type 1 AARF according to the
      classification of Li and Pang. The patient was treated with halter traction of 5
      lb weight for 6 weeks, and with a brace for 4 months and collar for 2 months.
      RESULTS: We successfully treated this patient with chronic AARF only with
      cervical traction. She had full recovery of neck motion and normal atlantoaxial
      angle on follow-up computerized tomography after 6 months. CONCLUSION: From this
      case, we suggest that long-term traction could be another treatment method for
      chronic AARF, especially in children.

PMID- 16094265
TI  - Computerized tomography guided sacroplasty: a practical treatment for sacral
      insufficiency fracture: case report.
AB  - STUDY DESIGN: Small case series projecting widespread therapeutic implications.
      OBJECTIVE: To promote sacroplasty as a feasible treatment for sacral
      insufficiency fractures. SUMMARY OF BACKGROUND DATA: Osteoporosis, a major cause
      of vertebral and sacral insufficiency fractures, is an increasingly serious
      problem in the elderly population. Painful sacral fractures often cause patients
      to be immobile, and at increased risk for comorbidities and osteoporosis
      progression. Currently, there is no therapy available for the treatment of these
      fractures. Vertebroplasty has evolved as a standard of care for treating
      fractures as a result of malignant and nonmalignant spinal pathology. Sacroplasty
      represents a reasonable adaptation of this interventional technique. METHODS:
      Computerized tomography (CT) guidance was used to monitor percutaneous
      polymethylmethacrylate injection into sacral insufficiency fractures. RESULTS: We
      report 2 cases of elderly patients with posttraumatic sacral insufficiency
      fractures, whose symptoms were completely relieved following CT-guided internal
      fixation by percutaneous polymethylmethacrylate injection. CONCLUSION: Under CT
      guidance, sacroplasty is a safe, practical, and effective solution to this
      underdiagnosed problem, with potential for comorbidities resulting in prolonged,
      costly hospital admissions for the elderly.

PMID- 16094267
TI  - Efficacy of dilute betadine solution irrigation in the prevention of
      postoperative infection of spinal surgery.
AB  - STUDY DESIGN: Prospective, single-blinded, randomized study. OBJECTIVES: To
      evaluate the efficacy of dilute betadine irrigation of spinal surgical wounds in
      prevention of postoperative wound infection. SUMMARY AND BACKGROUND: Deep wound
      infection is a serious complication of spinal surgery that can jeopardize patient
      outcomes and increase costs. Povidoneiodine is a widely used antiseptic with
      bactericidal activity against a wide spectrum of pathogens, including methicillin
      resistant Staphylococcus aureus. The aim of this study was to evaluate the
      efficacy of dilute betadine solution in the prevention of wound infection after
      spinal surgery. METHODS: Four hundred and fourteen patients undergoing spinal
      surgery were randomly assigned to two groups. In group 1 (208 patients), surgical
      wounds were irrigated with dilute betadine solution (3.5% betadine) before wound
      closure. Betadine irrigation was not used in group 2 (206 patients). Otherwise,
      perioperative management was the same for both groups. RESULTS: Mean length of
      follow-up was 15.5 months in both groups (range, 6-24 months). No wound infection
      occurred in group 1. One superficial infection (0.5%) and six deep infections
      (2.9%) occurred in group 2. The differences between the deep infection rate (P =
      0.0146) and total infection rate (P = 0.0072) were significant between the two
      groups. CONCLUSIONS: Our report is the first prospective, single-blinded,
      randomized study to evaluate the clinical effectiveness of dilute betadine
      solution irrigation for prevention of wound infection following spinal surgery.
      We recommended this simple and inexpensive measure following spinal surgery,
      particularly in patients with accidental wound contamination, risk factors for
      wound infection, or undergoing surgery in the absence of routine ultraviolet
      light, laminar flow, and isolation suits.

PMID- 16094268
TI  - Initial fusion rates with recombinant human bone morphogenetic protein
      2/compression resistant matrix and a hydroxyapatite and tricalcium
      phosphate/collagen carrier in posterolateral spinal fusion.
AB  - STUDY DESIGN: Prospective, randomized, unblinded study of iliac crest bone graft
      (ICBG) versus recombinant human bone morphogenetic protein-2/compression
      resistant matrix (rhBMP-2/CRM)in a posterolateral instrumented fusion procedure.
      OBJECTIVES: Document initial radiographic characteristics, based on computed
      tomography, with rhBMP-2/CRM for posterolateral fusion at 6 and 12-month
      intervals. SUMMARY OF BACKGROUND DATA: As the acceptance of INFUSE bone graft as
      an ICBG replacement becomes more widespread, surgeons have begun to study
      applications for rhBMP-2 in posterior spinal fusion. Preclinical studies have
      examined variables including carrier composition, rhBMP-2 concentration, and
      rhBMP-2 dose. Pilot studies have been performed with encouraging initial results.
      METHODS: Patients with single level lumbar degenerative disease were enrolled in
      a randomized study of ICBG versus rhBMP-2/CRM in a posterolateral instrumented
      fusion procedure. Computed tomography scans at 6 and 12 months were graded as
      demonstrating no fusion (grade 1), partial or limited unilateral fusion (grade
      2), partial or limited bilateral fusion (grade 3), solid unilateral fusion (grade
      4), or solid bilateral fusion (grade 5). RESULTS: At our institution, 74 patients
      (38 rhBMP-2/CRM, 36 ICBG) reached minimum 1-year follow-up and were included in
      this analysis. Mean fusion grade (scale1-5) at 6 months after surgery was 4.35 in
      the rhBMP-2/CRM group versus 3.09 in the ICBG group (P < 0.0001). At 1 year after
      surgery mean fusion grade was 4.62 in the rhBMP-2/CRM group versus 3.77 in the
      ICBG group (P < 0.0023). CONCLUSIONS: These early results are encouraging and
      suggest a more rapid incorporation and development of the fusion mass with rhBMP
      2/CRM than iliac crest autograft in a single level posterior instrumented fusion.

PMID- 16094269
TI  - Effect of mechanical compression on the lumbar nerve root: localization and
      changes of intraradicular inflammatory cytokines, nitric oxide, and
      cyclooxygenase.
AB  - STUDY DESIGN: Investigation of intraradicular inflammation induced by mechanical
      compression. OBJECTIVE: To investigate the mechanism of nerve root pain, this
      study used a lumbar nerve root compression model. SUMMARY OF BACKGROUND DATA: The
      manifestation of pain at sites of inflammation has a close relationship with the
      release of mediators from macrophages. However, the mediators involved in
      inflammation of nerve roots as a result of mechanical compression remain almost
      unknown. METHODS: In this study, the seventh lumbar nerve root of dogs was
      compressed with a clip for 3 weeks to observe the changes caused by compression.
      Immunohistochemistry was performed using the avidin-biotin-peroxidase complex
      method to observe the changes of T cells (CD45) and macrophages (Mac-1) after
      compression. Antibodies against as interleukin-1 (IL-1), tumor necrosis factor
      alpha (TNF-alpha), inducible nitric oxide synthase (i-NOS), and cyclooxygenase
      (COX)-1 and 2 were used to examine the localization and changes of these
      mediators caused by nerve root compression. RESULTS: In control animals, resident
      T cells were detected, but there were no macrophages. IL-1beta and COX-2 were
      positive in the Schwann cells and vascular endothelial cells, while COX-1 was
      detected in the vascular endothelial cells. However, no cells showed TNF-alpha or
      i-NOS positively. After nerve root compression, numerous T cells and macrophages
      appeared among the demyelinized nerve fibers. The macrophages were positive for
      IL-1beta, TNF-alpha, i-NOS, and COX-2. CONCLUSION: Inflammatory cytokines, NO,
      and COX-2 may be deeply involved in radiculitis caused by mechanical compression,
      and these mediators seem to be important in the manifestation of root pain.

PMID- 16094270
TI  - Estrogen-dependent actions of bone morphogenetic protein-7 on spine fusion in
      rats.
AB  - STUDY DESIGN: Intertransverse process spinal fusion using recombinant human bone
      morphogenetic protein-7 (rhBMP-7) was performed in intact and ovariectomized
      female rats. OBJECTIVES: To examine fusion rates in intact and ovariectomized
      female rats using rhBMP-7 to determine if spine fusion is dependent on estrogen
      status. SUMMARY OF BACKGROUND DATA: Rat spinal fusion has been established as a
      consistent, efficient model for posterolateral intertransverse process fusion.
      Previous experiments have confirmed the efficacy of pellets containing the
      carrier, insoluble collagen bone matrix (ICBM), and rhBMP-7 to augment
      intertransverse process single level fusion in a rat model. Studying these
      implications in an osteoporosis model is of clinical value because there are many
      patients undergoing spinal fusion surgery that have osteoporotic bone disease,
      and there is a steady increase in this group of patients. METHODS: A total of 15
      ovariectomized and 15 intact Sprague-Dawley female rats were randomly assigned to
      groups receiving 25 mg ICBM alone, 25 mg ICBM + 10 microg rhBMP-7, and 25 mg ICBM
      + 30 microg rhBMP-7. Spinal fusion was evaluated by manual motion testing at each
      lumbar segment, radiographic evaluation using the Lenke grading system, and
      histology. RESULTS: Ovariectomized and intact rats receiving 25 mg carrier ICBM
      alone did not show spinal fusion. With 25 mg ICBM + 10 microg rhBMP-7, there was
      not a significant difference in fusion rates between intact and ovariectomized
      rats (P = 0.63). Ovariectomized rats receiving 25 mg ICBM + 30 microg rhBMP-7
      showed significantly lower fusion rates than intact rats (P = 0.013). CONCLUSION:
      These data suggest that spinal fusion using rhBMP-7 is estrogen-dependent in
      rats. At the dosages used, rhBMP-7 was unable to overcome the inhibitory effects
      of estrogen deficiency on spinal fusion.

PMID- 16094271
TI  - Incision of the intervertebral disc induces disintegration and increases
      permeability of the dorsal root ganglion capsule.
AB  - STUDY DESIGN: The origin and the barrier properties of the characteristic
      reaction at the surface of the dorsal root ganglion (DRG) exposed to the nucleus
      pulposus was studied using Alcian-Blue staining, van Gieson staining, and the
      application of Evans Blue Albumin (EBA) complex in rats. OBJECTIVE: To study the
      origin and the barrier properties of the capsule, including the characteristic
      reaction, at the surface of the DRG exposed to the nucleus pulposus. SUMMARY OF
      BACKGROUND DATA: Local application of nucleus pulposus may induce a
      characteristic reaction at the surface of the DRG. This reaction histologically
      resembles an acute inflammatory reaction. However, it is not evident if this is a
      swelling of the DRG capsule, if it is located between the capsule and neurons of
      the DRG, or if it is only an attached nucleus pulposus. METHODS: Nucleus pulposus
      from the discs was obtained. The nucleus pulposus was smeared on glass slides.
      Alcian-Blue with hematoxylin and eosin staining was performed for each smear.
      Herniation of the nucleus pulposus was made in the L4-L5 disc in rats. The L4
      DRGs were resected 3, 24, and 72 hours after surgery, and sectioned. The sections
      were processed for Alcian-Blue staining, van Gieson staining, and EBA complex
      infiltration. The sections were observed using light or fluorescent microscopy.
      RESULTS: Smear of nucleus pulposus was stained bright blue indicating mucins. A
      characteristic reaction, "inflammatory crescent," was confirmed at the surface of
      the DRG exposed to the nucleus pulposus. No mucins were observed in the crescent
      using Alcian-Blue. The results of van Gieson staining showed that the reaction
      started both inside and outside the elastic fiber layer, the DRG capsule, within
      3 hours. The EBA complex was capable of infiltrating into the DRG capsule 24
      hours after disc incision. CONCLUSIONS: The disintegrated capsule showed an
      increased permeability even for a large molecule as albumin, which indicates a
      possible entrance route for various substances induced by locally applied nucleus
      pulposus.

PMID- 16094272
TI  - Experimental spinal fusion with recombinant human bone morphogenetic protein-2
      delivered by a synthetic polymer and beta-tricalcium phosphate in a rabbit model.
AB  - STUDY DESIGN: An experimental animal study to achieve posterolateral
      intertransverse process spine fusion with recombinant bone morphogenetic protein
      in combination with a new delivery system. OBJECTIVE: To evaluate the efficacy of
      a new synthetic biodegradable bone-inducing material containing recombinant human
      bone morphogenetic protein-2 (rhBMP-2) as a bone-graft substitute for
      posterolateral intertransverse process fusion in a rabbit model. SUMMARY OF
      BACKGROUND DATA: rhBMP-2, a powerful bone-inducing cytokine, has been used as a
      bone graft substitute in combination with animal-derived collagen to achieve
      spinal fusion in animal models. However, the minimum dose of rhBMP-2 required to
      obtain solid posterolateral intertransverse process fusion was high on the basis
      of previous reports (>100 microg in rabbit models). To improve the efficacy,
      performance of rhBMP-2, and the safety of the delivery system for this protein, a
      more sophisticated system is required. METHODS: To fabricate one implant for one
      side L4-L5 intertransverse process fusion, beta-tricalcium phosphate (beta-TCP)
      powder (300 microg), a polymer gel (PLA-DX-PEG block copolymer; 300 microg) and
      rhBMP-2 (7.5, 15, or 30 microg) were mixed and manually shaped to resemble a rod.
      Through a posterolateral approach, two implants were placed on both sides (1 per
      side) by surgery so as to bridge the transverse processes of adult New Zealand
      white rabbits (n = 27). In control animals, implants without rhBMP or autogenous
      cortico-cancellous bone chips from the iliaccrest were placed in a similar
      location. The lumbar vertebrae were recovered 6 weeks after surgery. The
      posterolateral fusion was examined by manual palpation, radiography,
      biomechanical testing, and histology. RESULTS: Rabbits that received 15 or 30
      microg of rhBMP-2 showed consistent fusion. However, solid fusion was seen in 2
      of 5 rabbits with autografting and rabbits that received 7.5 microg of rhBMP-2.
      Fusion was not observed in the rabbits that did not receive rhBMP-2. CONCLUSIONS:
      Consistent spinal fusion was obtained by implanting a biodegradable bone-inducing
      implant composed of beta-TCP, PLA-DX-PEG, and rhBMP-2 within a period of 6 weeks.
      The rhBMP-2 doses required for the spinal fusion were significantly lower than
      those reported previously.

PMID- 16094273
TI  - Can vertebroplasty restore normal load-bearing to fractured vertebrae?
AB  - STUDY DESIGN: Cadaver motion segments were used to evaluate the effects of
      vertebroplasty on spinal loading following vertebral fracture. OBJECTIVES: To
      determine if vertebroplasty reverses fracture-induced changes in the distribution
      of compressive stress in cadaver motion segments. SUMMARY OF BACKGROUND DATA:
      Vertebroplasty involves reinforcement of vertebrae by injection of cement and is
      now being used increasingly to treat osteoporotic vertebral fractures. However,
      its effects on spinal load-bearing are largely unknown. We hypothesize that
      vertebroplasty, following vertebral fracture, helps to equalize stress acting on
      the intervertebral disc and adjacent vertebral bodies. METHODS: Nineteen cadaver
      thoracolumbar motion segments (age 64-90 years) were induced to fracture by
      compressive overload. Specimens were then subjected to vertebroplasty, and
      subsequently creep loaded for 1 hour at 1.5 kN. The compressive stress acting on
      the intervertebral disc was measured before and after fracture, after
      vertebroplasty, and after creep, by pulling a pressure transducer mounted in a
      1.3-mm needle across the disc's midsagittal diameter. This information was then
      used to calculate neural arch load-bearing. At each time point, measurements were
      also made of compressive stiffness. RESULTS: Vertebral fracture reduced motion
      segment compressive stiffness, decompressed the adjacent nucleus, increased
      stress concentrations in the posterior anulus, and increased neural arch load
      bearing, all by a significant amount. Vertebroplasty partially, but
      significantly, reversed all of these fracture-induced changes. CONCLUSIONS:
      Vertebroplasty reduces stress concentrations in the anulus and neural arch
      resulting in a more even distribution of compressive stress on the intervertebral
      disc and adjacent vertebral bodies.

PMID- 16094274
TI  - Analysis of stress distribution in lumbar interbody fusion.
AB  - STUDY DESIGN: A 2-dimensional axisymmetric finite element model of an
      intervertebral segment was used to investigate the stress patterns in the
      adjacent vertebrae of fused spinal segment incorporating 4 common cage designs.
      The same was used to study the effect of maturation of bone graft on stress
      distribution pattern. OBJECTIVES: To study and compare the stress distribution
      patterns in a normal spinal segment and in the adjacent vertebrae of a fused
      spinal segment. The effect of bone graft incorporation around the mesh cage was
      also investigated. SUMMARY OF BACKGROUND DATA: Lumbar fusion surgery is thought
      to relieve discogenic low back pain by eliminating the abnormal intersegmental
      movement at the level of disc degeneration. Successful spinal fusion does not
      guarantee symptomatic pain relief. Discogenic pain is also known to be associated
      with an abnormal load transmission pattern across the degenerate disc. We
      hypothesized that the lumbar interbody fusion results in relief of discogenic
      pain by normalizing the load distribution pattern. METHODS: We used a 2
      dimensional axisymmetric finite element model of an intervertebral segment to
      investigate the stress patterns in the vertebrae adjacent to a fused spinal
      segment incorporating 4 common cage designs: (1) anterior lumbar interbody
      fusion, (2) posterior lumbar interbody fusion rectangular, (3) posterior lumbar
      interbody fusion threaded, and (4) mesh cage. RESULTS: High stress concentrations
      and abnormal overall stress patterns were noted for all the cage designs studied.
      The anterior lumbar interbody fusion cage with its larger contact area showed the
      least abnormal stress magnitude in comparison with the other cages. Incorporation
      of bone in and around the mesh cage increased the area of contact and decreased
      the abnormal high stresses. The spine fusion model representing final bony
      healing showed restoration of near physiologic stress pattern. CONCLUSIONS:
      Interbody fusion cages with larger area of contact between cage and vertebral
      endplate produces a lower stress distribution pattern. A successful bony fusion
      restores near physiologic stress distribution pattern. Restoration of near normal
      load distribution pattern may become an important aim of surgery for discogenic
      low back pain.

PMID- 16094275
TI  - Distractable vertebral cages for reconstruction after cervical corpectomy.
AB  - STUDY DESIGN: Retrospective study of 20 patients with degenerative cervical
      spinal canal stenosis who were treated with corpectomy followed by the placement
      of a distractable titanium cage (anterior distraction device [ADD]) (Ulrich GmbH
      & Co. KG, Ulm, Germany). OBJECTIVE: To investigate the efficacy of distractable
      titanium cages for reconstruction following decompressive cervical corpectomy.
      SUMMARY OF BACKGROUND DATA: Anterior corpectomy and reconstruction for extensive
      spinal canal stenosis are standard techniques. The reconstruction is commonly
      performed with bone graft and anterior plating. Alternatively, different fusion
      cages have gained acceptance in spine surgery. However, in traditionally designed
      cages, an over-distraction of the involved segment is necessary to place the cage
      into the defect, and to achieve tight contact between cage and endplates. The new
      designed cage (ADD) can be distracted in situ. Therefore, the height of the cage
      can be adjusted precisely to the size of the corpectomy. METHODS: All patients
      were treated with corpectomy followed by the placement of an ADD. A cervical
      plate was added in 13 cases, and an "All-in-one-system" (i.e., a cage with an
      attached plate with 2 holes for screw fixation on both sides, ADD) was used in 7.
      Follow-up was 18-60 months. Clinical evaluation and radiographs were performed
      after 3, 6, and 12 months, and then once a year. RESULTS: In all cases, a stable
      reconstruction of the anterior column was achieved, with no signs of instability
      on flexion/extension radiographs. However, there was one incidence of cage
      subsidence. According to Odom criteria, 11 patients (55%) had excellent outcome,
      4 (20%) good, 3 (15%) satisfactory, and 2 (10%) poor. CONCLUSIONS: The results of
      the study show that distractable cages are useful vertebral body replacements
      because they can be adjust to the size of the corpectomy in situ and provide
      immediate strong anterior column support, avoiding bone graft site morbidity. The
      possibility of direct cage fixation without an additional plate simplifies the
      procedure.

PMID- 16094276
TI  - The effect of trunk flexion in healthy volunteers in rear whiplash-type impacts.
AB  - STUDY DESIGN: Twenty young, healthy volunteers in a laboratory were subjected to
      rear-end impacts 4.4, 7.9, 10.9, and 13.1 m/s acceleration with head rotation to
      right and left. OBJECTIVES: The purpose of this study was to determine the
      response of the cervical muscles to increasing low-velocity rear impacts when the
      head is rotated at the time of impact. SUMMARY OF BACKGROUND DATA: A previous
      study of rear impacts with head in neutral posture suggests that the burden of
      impact is borne primarily by the sternocleidomastoid muscles bilaterally. To
      improve automobile designs to prevent whiplash injury, we need to understand the
      response of the cervical muscles to whiplash-type perturbations in other
      conditions that mimic road collisions, such as when the head is rotated to the
      right and left at the time of rear-end impact. METHODS: Triaxial accelerometers
      recorded the acceleration of the sled, torso at the shoulder level, and head of
      the participant, while bilateral electromyograms (EMGs) of the
      sternocleidomastoids, trapezii, and splenii capitis were also recorded on 20
      subjects (10 males and 10 females, mean age of 23.6 +/- 3 years) RESULTS: For
      participants experiencing a rear-end impact, whether having the head rotated to
      the left or right at the time of impact, the muscle responses increased with
      increasing levels of acceleration (P < 0.01). The time to onset and time to peak
      EMG for all muscles progressively decreased with increasing levels of
      acceleration (P < 0.01). Which muscle responded most to a whiplash-type neck
      perturbation was determined by the direction of head rotation. With the head
      rotated to the left, the right sternocleidomastoid generated 88% of its maximal
      voluntary contraction EMG (at least triple the response of other muscles). In
      comparison, the left sternocleidomastoid, both trapezii, and the splenii capitis
      generated on average only 10 to 30% of their maximal voluntary contraction EMG
      with head rotated to the left. On the other hand, with the head rotated to the
      right, the left sternocleidomastoid generated 94% of its maximal voluntary
      contraction EMG (again, at least triple the response of other muscles).
      CONCLUSIONS: If the head is rotated out of neutral posture at the time of rear
      impact, the injury risk tends to be greater for the sternocleidomastoid muscle
      contralateral to the side of rotation. Measures to prevent whiplash injury may
      have to account for the asymmetric response because many whiplash victims are
      expected to be looking to the left or right at the time of collision.

PMID- 16094277
TI  - A prospective cohort analysis of adjacent vertebral body bone mineral density in
      lumbar surgery patients with or without instrumented posterolateral fusion: a 9-
      to 12-year follow-up.
AB  - STUDY DESIGN: A prospective, cohort study of 11 patients who underwent either a
      posterior lumbar spinal fusion with instrumentation (n = 7) or a lumbar
      laminotomy and discectomy alone (n = 4) and who were evaluated by dual energy
      radiograph absorptiometry (DEXA) to determine bone mineral density (BMD) at the
      adjacent three cephalad vertebral levels. OBJECTIVES: To determine long-term BMD
      changes that occur at the adjacent three levels above an instrumented
      posterolateral lumbar fusion or an isolated laminotomy and lumbar discectomy.
      SUMMARY OF BACKGROUND DATA: No long-term prospective study has evaluated the
      affects of instrumented lumbar fusions on bone remodeling at adjacent vertebral
      levels. Several studies in animals and humans have reported a decrease in BMD at
      the adjacent level during the first 6 months after spinal fusion with a return to
      baseline at 1-year follow-up in up to 60% of patients. METHODS: DEXA was
      performed initially at a mean postoperative follow-up of 4 years (range, 2.3-5.5
      years) and again at a mean of 10.8 years (range, 9.1-2.4 years). Eleven patients
      were divided into two groups: laminotomy and discectomy (n = 4) and instrumented
      posterior spinal fusion (n = 7). All patients underwent surgical procedures at
      the L4-L5 or L5-S1 levels with DEXA analysis being performed on the adjacent
      three cephalad levels. The discectomy group (mean age, 57.8 years) underwent
      lumbar hemilaminotomy without fusion whereas the other group (mean age, 60 years)
      underwent pedicle-screw instrumentation and posterolateral lumbar fusion.
      Peripheral sites, including the femoral neck, were included in the DEXA analysis
      to normalize for individual differences in bone mineral metabolism. RESULTS: At
      the mean 10.8-year follow-up, the fusion group was noted to have at the adjacent
      level, two levels cephalad, and three levels cephalad normalized BMDs of 1.47,
      1.39, and 1.27, respectively. A 14.8%, 10.8%, and 9.5% increase respectively in
      normalized BMD was observed when compared with the mean 4-year fusion values (P <
      0.05). This increase was also noted on comparative T-score, Z-score, and absolute
      BMD values (P < 0.05). The discectomy group when evaluated revealed no
      statistically significant change from the mean 4 to 10.8-year follow-up (BMD,
      normalized BMD, T-score, Z-score). No statistically significant difference was
      noted in hip BMD at the mean 4-year and 10.8-year follow-up (1.05 versus 1.03),
      suggesting that the effects were local. CONCLUSIONS: The local BMD adjacent to an
      instrumented lumbar fusion is increased at a mean of 10.8-years after surgery.
      There is a gradual decrease in BMD changes with increasing distance from the
      fusion level. Alterations in fusion site biomechanics and modulus mismatch
      between the host bone and the spinal instrumentation most likely result in
      chronic, localized bone remodeling with an increased BMD that decreases the
      greater the distance from the fusion mass.

PMID- 16094278
TI  - Is autograft the gold standard in achieving radiographic fusion in one-level
      anterior cervical discectomy and fusion with rigid anterior plate fixation?
AB  - STUDY DESIGN: A review of 66 consecutive patients at a single institution who
      underwent one-level anterior cervical discectomy and fusion (ACDF) with rigid
      anterior plate fixation with allograft or autograft. OBJECTIVES: To address the
      efficacy of allograft to autograft with primary respect to fusion rate and
      secondary attention to risk factors and clinical outcome in patients undergoing
      one-level ACDF with rigid anterior plate fixation. SUMMARY OF BACKGROUND DATA:
      Although autograft is considered the gold standard in achieving optimal fusion,
      when compared with allograft in noninstrumented one-level ACDF and in plated and
      nonplated multilevel ACDF, the efficacy of allograft to autograft in one-level
      ACDF with rigid anterior plate fixation is not thoroughly understood. METHODS:
      Sixty-six consecutive patients (mean age, 45 years) at a single institution who
      underwent one-level ACDF with rigid anterior plate fixation with allograft (n =
      35) or autograft (n = 31) were reviewed for radiographic fusion (mean, 12
      months), risk factors, and clinical outcome (mean, 17 months). Smokers entailed
      33.3% of the patients, and 45.5% of all patients presented with a work-related
      injury. An independent blinded observer reviewed at last follow-up lateral
      neutral and flexion/extension plain radiographs for radiographic fusion and
      instrumentation integrity. Clinical outcome was assessed on last follow-up and
      rated according to the Odom criteria. The threshold for statistical significance
      was established at P < 0.05. RESULTS: Solid fusion was achieved in 63 patients
      (95.5%). Fusion was noted in 100% of the allograft patients, whereas 90.3% of the
      autograft cases achieved fusion. No statistically significant difference was
      noted between allograft to autograft with regard to fusion rate (P > 0.05). Three
      patients developed nonunions (1 smoker; 2 nonsmokers) and entailed Orion
      instrumentation. In the one patient who was a nonsmoker with a nonunion, slight
      screw penetration into the involved and uninvolved interbody spaces was noted. No
      other intraoperative, postoperative, or radiographic complication was noted. All
      of the nonunions occurred early in the series. Postoperatively, excellent results
      were reported in 19.7%, good results in 71.2%, and fair results in 9.1% of the
      patients. Satisfactory clinical outcome was noted in all nonunion patients. A
      nonstatistically significant difference was noted with regard to clinical outcome
      of fused and nonfused patients, demographics, and the presence of a work-related
      injury (P > 0.05). The impact of smoking was not a factor influencing fusion or
      clinical outcome in this series (P > 0.05). A statistically significant
      difference was noted in plate-type on fusion rate (P < 0.05). CONCLUSION: A 100%
      and 90.3% radiographic fusion rate was obtained for allograft and autograft in
      one-level ACDF procedures with rigid anterior plate fixation, respectively.
      Although autograft achieved a higher incidence of nonunion than allograft, this
      may be attributed to the use of autograft early in the experience of plate
      application and fixation in this series. The effects of smoking were not found to
      be a significant factor influencing fusion in these plated patients. In 90.9% of
      the patients, excellent and good clinical outcome results were reported. The use
      of allograft in one-level ACDF with rigid plate fixation yields similar and high
      fusion rates as autograft. The use of allograft bone eliminates complications and
      pitfalls associated with autologous donor site harvesting. However, the use of
      autograft is a viable alternative to avoid the risk of infection, disease
      transmission, and histocompatibility differences associated with allograft. The
      use of allograft or autograft bone in properly selected patients for one-level
      ACDF with rigid anterior plate fixation can result in high fusion rates with
      excellent and good clinical outcomes.

PMID- 16094279
TI  - Ultrastructural immunolocalization of alpha-elastin and keratan sulfate
      proteoglycan in normal and scoliotic lumbar disc.
AB  - STUDY DESIGN: Comparative ultrastructural study of intervertebral discs from
      normal subjects and patients with scoliosis. OBJECTIVE: To identify
      ultrastructural relations among keratan sulfate (KS) proteoglycan, alpha-elastin,
      collagen fibers, and elastic fibers in normal and scoliotic discs. SUMMARY OF
      BACKGROUND: KS proteoglycans, elastic fibers, and collagen fibers play important
      mechanical roles in the intervertebral disc, but the distributions of KS
      proteoglycans and elastin in this tissue have received little attention. METHODS:
      Tissues were fixed in 4% paraformaldehyde. Monoclonal antibody 5-D-4 (which
      recognizes a KS epitope on aggrecan, fibromodulin, and lumican) and polyclonal
      anti-alpha-elastin were visualized with a 10-nm immunogold-conjugated secondary
      antibody. RESULTS: In a normal disc, a regular pattern of KS labeling occurred
      around collagen fibers, in the cell cytoplasm, and in the rough endoplasmic
      reticulum; the nucleus pulposus was more densely labeled for KS than was the
      anulus fibrosus. In scoliotic disc anulus fibrosus, KS labeling was weak
      throughout the matrix and pericellularly but abundant in lysosomes and on
      electron-dense material in degenerate cells. Degenerate collagen fibers in
      scoliotic tissue bore less KS than did normal fibers. KS labeling of the
      microfibrillar region of elastic fibers was strong in normal disc but weak in
      scoliotic disc. Elastin labeling of elastic fibers was weaker in scoliotic than
      in normal tissue. CONCLUSION: KS proteoglycans and elastic fibers are closely
      associated with the lamellar organization of the collagen fibers in a normal
      disc. In scoliosis, impaired regulation of collagen fibrillogenesis by lumican or
      fibromodulin may result in disruption of the lamellar structure.

PMID- 16094280
TI  - Beliefs about low back pain in the Norwegian general population: are they related
      to pain experiences and health professionals?
AB  - STUDY DESIGN: A baseline study of the general population and the health care
      providers in 3 Norwegian counties. OBJECTIVE: To investigate if beliefs about low
      back pain (LBP) are related to personal experiences and profession sought for
      care. SUMMARY OF BACKGROUND DATA: Myths about LBP that are abandoned by health
      professionals are still alive in the public. Such myths represent pain avoidance
      beliefs and passive coping strategies that may hinder normal spontaneous recovery
      from an episode of LBP. METHODS: A sample of 1502 randomly selected people was
      interviewed by telephone, and all the 1105 physicians, physiotherapists, and
      chiropractors in the area were sent a questionnaire in April 2002. All
      respondents gave their responses in terms of degree of agreement to 6 statements
      reflecting beliefs about LBP. RESULTS: Personal back pain experiences were
      important for beliefs about LBP. People with a history of previous back pain had
      more faith in the 2 statements "Back pain recovers best by itself" (52.2%) and
      "In most cases back pain recovers by itself in a couple of weeks" (32.5%) than
      those with current pain (36.9% and 20.9%, respectively, P < 0.000). There were
      significant differences in beliefs between physicians and the chiropractors
      concerning the same 2 statements, and these differences were also reflected in
      the beliefs of patients treated by the different professional groups.
      CONCLUSIONS: Belief in spontaneous recovery from LBP seems to be positively
      correlated to previous experience with LBP without current pain. Patients of the
      various health care providers seem to have a faith in spontaneous recovery
      similar to that of their health care provider. These differences may frustrate
      the public and patients who visit more than one provider, and hinder
      collaboration among professional groups.

PMID- 16094281
TI  - Burden of illness of chronic low back pain in Sweden: a cross-sectional,
      retrospective study in primary care setting.
AB  - STUDY DESIGN: Cross-sectional survey of patients with chronic low back pain in
      primary care setting. OBJECTIVES: To analyze the health care resource use,
      productivity loss, and health-related quality of life of patients with chronic
      low back pain in Sweden. SUMMARY OF BACKGROUND DATA: Despite the clinical and
      economic importance of chronic LBP, the overall burden of the disease is not well
      documented. METHODS: Cross-sectional data on patients' socio-demographics,
      disease-related healthcare resource use during the past 6 months, inability to
      work during the previous 3 months, and quality of life at the time of the study
      visit were collected using questionnaires completed during an outpatient visit.
      Patient recruitment and data collection was performed at 14 primary care centers
      in Sweden. Patients over 18 years of age with chronic LBP present at least 50% of
      the days during the previous 3 months were included. Regression analysis was used
      to investigate factors associated with variation in costs. RESULTS: Based on a
      sample of 302 patients, the total annual direct costs for chronic LBP per patient
      were estimated at 3,100 Euros, or 2,900 United States dollars, in 2002 prices,
      constituting 15% of the total annual LBP costs per patient. The indirect costs
      (mainly productivity loss because of lost work days) were estimated at 17,600
      Euros (16,600 United States dollars) per patient, or 85% of the total LBP costs
      per patient. Direct and indirect costs were positively correlated with disease
      severity, disease duration, and female gender. The mean Roland & Morris score was
      12.2, and the Medical Outcomes Study 8-Item Short Form physical and mental
      summary component scores were 35.2 and 41.6, respectively. CONCLUSIONS: In
      Sweden, the indirect costs for chronic LBP appear to be substantially higher than
      the direct costs for pharmaceuticals, medical visits, physiotherapy,
      andhospitalizations. The high indirect costs indicate that more effective
      treatments for chronic LBP could potentially lead to cost savings even if the
      therapy costs were higher.

PMID- 16094282
TI  - The transition from acute to subacute and chronic low back pain: a study based on
      determinants of quality of life and prediction of chronic disability.
AB  - STUDY DESIGN: Follow-up study. OBJECTIVES: To document differences between acute
      and subacute low back pain (LBP) based on the risk of developing chronic
      disability and on the correlation between pain, disability, and quality of life.
      SUMMARY OF BACKGROUND DATA: The subacute stage should identify the time in which
      the risk of developing chronic disability increases and specific measures should
      be considered, but its definition is currently inconsistent. METHODS: 366
      patients were given Visual Analog Scales (VAS) for LBP and referred pain (RP),
      Roland-Morris questionnaires (RMQs), and EuroQol (EQ) questionnaires on their
      first visit and 14 and 59 days later. RESULTS: Median duration of pain when
      entering the study was 4 days (P25, P75: 2,10). Simple correlations among LBP,
      VAS, and RMQ were r = 0.407 (day 1), 0.688 (day 15), and 0.739 (day 60). Among
      LBP, VAS, and EQ, r = -0.523, r = -0.701, and r = -0.760. Among RP, VAS, and RMQ,
      r = 0.280, r = 0.561, and r = 0.583. Between RP, VAS, and EQ, r = -0.306, r = 
      0.534 and r = -0.600. Between RMQ and EQ, r = -0.650, r = -0.765 and r = -0.815.
      In 42 patients, disability did not improve throughout the study period, and a
      prestudy duration of > or = 14 days was the only independent predictor. All these
      models were significant at the P < 0.007 level. Improvement in quality of life
      was more likely to occur in patients in which disability improved [odds ratio
      (OR), 18.29; 95% CI; 8.64, 38.73; P < 0.001]. As opposed to acute patients, in
      those with a prestudy duration of pain of > or = 14 days, on day 60 RP had no
      influence on disability, and LBP had no influence on quality of life. CONCLUSION:
      LBP influences disability and quality of life more than RP. Disability is
      predicted by pain duration and quality of life is predicted by disability, but
      pain severity predicts neither one of them. Changes related to determinants of
      disability and quality of life, and to the prediction of chronic disability,
      appear 14 days after the onset of pain, supporting that cutoff point for
      considering a patient as being subacute.

PMID- 16094284
TI  - Self-reported asthma among high school students--United States, 2003.
AB  - Asthma is a leading chronic illness among children in the United States. To
      examine self-reported asthma and asthma attacks among U.S. high school students,
      CDC analyzed data from the 2003 national Youth Risk Behavior Survey (YRBS). This
      report summarizes the results of that analysis, which indicated that 18.9% of
      high school students had been told by a doctor or nurse that they had asthma,
      16.1% had current asthma, and 37.9% of those with current asthma had had an
      episode of asthma or an asthma attack during the 12 months preceding the survey.
      These findings underscore the need for health-care providers, schools, families,
      and public health practitioners to be prepared to respond to asthma-related
      emergencies and to help students manage their asthma.

PMID- 16094283
TI  - Accuracy of computerized frameless stereotactic image-guided pedicle screw
      placement into previously fused lumbar spines.
AB  - STUDY DESIGN: A retrospective chart and radiographic review of 122 pedicle screws
      placed with computerized stereotactic image-guidance into posterolateral fusion
      masses. OBJECTIVES: To determine the accuracy rate of computerized stereotactic
      image-guided pedicle screw placement in previously fused lumbar spines. SUMMARY
      OF BACKGROUND DATA: Placement of pedicle screws into a previously fused lumbar
      spine is challenging. The normal anatomic landmarks used to determine the
      starting point and trajectory of the screws have either been removed or are
      obscured by the fusion mass. Computerized frameless stereotaxis provides precise
      intraoperative real time multiplanar image-guidance and may be valuable in this
      clinical situation. METHODS: Computerized frameless stereotactic image-guidance
      was used to place pedicle screws into 78 consecutive patients with prior lumbar
      spine fusions. Postoperative computed tomography was available on 35 patients
      (231 screws). One hundred and twenty-two screws were placed into fusion masses.
      Pedicle cortical perforations were characterized by the direction (medial,
      inferior, lateral, or superior) and magnitude (in 2-mm increments) of
      perforation. RESULTS: Five (4.1%) of the 122 pedicle screws placed into
      previously fused levels were found to have unintentional cortical violations.
      There were 1 superior (<2 mm), 1 medial (<2 mm), and 3 lateral perforations (<2,
      4, and 6 mm). None of these perforations led to clinically apparent radicular
      pain or weakness. No pedicle screws required revision for malpositioning.
      CONCLUSIONS: The accuracy rate of stereotactic image-guided pedicle screw
      placement into previously fused lumbar spine levels is 96%. Computerized
      stereotactic image-guidance may have particular application in situations in
      which posterior element anatomy is altered, such as in the presence of a prior
      fusion mass.

PMID- 16094285
TI  - Human rabies--Florida, 2004.
AB  - Rabies is a viral infection of the central nervous system, usually contracted
      from the bite of an infected animal, and nearly always fatal without postexposure
      prophylaxis. In February 2004, a man aged 41 years died after a 4-day
      hospitalization in Broward County, Florida. A diagnosis of rabies was considered
      on the day before the patient's death; however, no antemortem samples were
      obtained for testing. In March 2004, postmortem samples of fixed brain material
      were sent to CDC, where laboratory testing confirmed a diagnosis of rabies, the
      47th case of human rabies reported in the United States since 1990 (CDC,
      unpublished data, 2005). This report summarizes results of the subsequent
      investigation led by the Broward County Health Department and laboratory testing
      at CDC, which determined that the rabies virus was a canine variant present in
      Haiti, where the man had traveled and reportedly been bitten by a dog. Rabies
      should be considered in persons after a dog bite, especially if the bite occurs
      in a country where canine rabies is enzootic.

PMID- 16094286
TI  - [Genotype analysis of the rRNA gene of Malassezia colonizing the skin surface of
      patients with atopic dermatitis].
AB  - Malassezia species are associated with pityriasis (tinea) versicolor, seborrheic
      dermatitis, and atopic dermatitis. Presently, eleven species are accepted in the
      genus Malassezia. Of these, M. globosa and M. restricta colonize the skin surface
      in atopic dermatitis patients, suggesting that they play a significant role in
      exacerbating the condition. The two species have different genotypes in the
      intergenic spacer (IGS) region of the rRNA gene, which correspond to patients and
      healthy individuals. In addition, the antifungal susceptibilities of the
      genotypic strains to itraconazole and ketoconazole differ. We found a new
      analytically significant role of the rRNA gene in Malassezia species, in addition
      to its use for fungal taxonomy and identification.

PMID- 16094287
TI  - [Phylogenetic relationship of the genus Malassezia based on mitochondrial
      cytochrome B gene].
AB  - Mitochondrial cytochrome b genes of pathogenic yeasts and fungi were analyzed for
      identification and phylogenetic relationship. The species of genus Malassezia
      also were analyzed and each sequence was specific in the same domain of
      cytochrome b gene. Some species represented intraspecies variation. The structure
      and function of cytochrome b protein was retained and its substitution rates may
      be in proportion to the evolutionary period. The deduced amino acid sequence was
      encoded by each nucleotide sequence of cytochrome b gene, and the phylogenetic
      tree of eukaryote and basidiomycetous yeast was obtained using this sequence. The
      species of genus Malassezia formed one cluster in this tree, meaning that the
      concepts of this genus reflect its evolution. The mitochondrial cytochrome b gene
      analysis was valuable for the identification and phylogenetic analysis of the
      genus.

PMID- 16094288
TI  - [Chitin Synthase 2 (CHS2) gene of Malassezia species].
AB  - Malassezia species have been recognized as members of the microbiological flora
      of human and animal skin; they are also considered to play an important role in
      the pathogenesis of folliculitis, atopic dermatitis and otitis externa.
      Therefore, the molecular characteristics were investigated to clarify the
      epidemiology and the pathogenesis of diseases associated with Malassezia species
      in human and animals. Molecular investigation was made of 105 clinical isolates
      of M. pachydermatis from dogs and cats by random amplification of polymorphic DNA
      (RAPD) and chitin synthase 2 (CHS2) gene sequence analyses. The RAPD analysis and
      CHS2 gene analysis indicated that clinical isolates of M. pachydermatis were
      divided into four distinct genetic types (A, B, C and D). Type A was isolated
      from lesions of atopic dermatitis, flea allergic dermatitis, otitis externa,
      pyoderma and seborrheic (dermatitidis) in dogs and cats, and might be predominant
      on this. The phylogenetic analysis of the nucleotide sequences of CHS2 gene
      fragments of standard strains of 11 Malassezia species showed 11 distinct
      clusters of this species.

PMID- 16094289
TI  - [Malassezia species in patients with seborrheic dermatitis and atopic
      dermatitis].
AB  - Malassezia species, organisms normally colonizing the skin surface, are thought
      to play a role as either the cause or an exacerbating factor in a number of skin
      conditions, including pityriasis versicolor, Malassezia folliculitis, seborrheic
      dermatitis (SD) and atopic dermatitis (AD). Using a non-cultural PCR method, we
      analyzed Malassezia spp. extracted from the skin surface of SD and AD patients.
      The species most commonly detected in both patient groups were M. globosa and M.
      restricta, and the number of Malassezia spp. In these patients was higher than in
      healthy subjects. After a topical application of 2% ketoconazole cream, changes
      in the population of Malassezia spp. in 20 intractable cases of AD were recorded.
      The addition of the 2% ketoconazole cream to the standard topical treatments was
      found to have reduced the Malassezia spp. population by 90%, and showed a
      clinical efficacy rate of 70%. Furthermore, a combination of azole agents and
      tacrolimus produced a synergistic anti-fungal effect against Malassezia spp. in
      vitro. A clinical trial using this drug combination conducted on the face and
      neck of patients with intractable AD showed a 66.6% efficacy rate in both the
      reduction of the flora and in clinical improvement. From these results it was
      evident that Malassezia is one of the factors exacerbating AD, and that removal
      of the organism results in an improvement in the clinical condition of the
      patient.

PMID- 16094290
TI  - [Examination of the causative agent of pityriasis versicolor].
AB  - Pityriasis versicolor (PV) is a superficial infection of the stratum corneum
      caused by Malassezia. Eleven species have been recognized within this genus,
      namely M. globosa, M. restricta, M. sympodiasis, M. furfur, M. obtusa, M.
      slooffiae, M. pachydermatis, M. dermatis, M. japonica, M. yamatoensis, M. nana.
      To examine the distribution of the microorganism in the skin of patients with PV,
      we detected Malassezia species without M. pachydermatis and M. nana using a non
      culture-based method that consisted of nested PCR with specific primers. The most
      frequently isolated species were M. globosa and M. restricta (both 93.9%). M.
      globosa was detected in scales in which only the mycelial form (yeast cells, <
      10/sample) were observed microscopically; M. restricta was not found. We suggest
      that M. globosa is the causative agent of PV.

PMID- 16094291
TI  - Epidemiology of onychomycosis in Indonesia: data obtained from three individual
      studies.
AB  - In terms of both diagnosis and treatment, onychomycosis remains a problem in
      Indonesia. To examine this situation, we performed a retrospective study of the
      incidence of onychomycosis involving 10 state university hospitals across the
      country. We collected data from medical records of patients treated at these
      hospitals in 1997-1998 (study 1) and from a 1998-1999 multi-center Indonesian
      study on pulse-dose itraconazole therapy (study 2), both of which were part of
      onychomycosis campaigns with the objective of increasing the awareness of
      physicians of onychomycotic problems. Further, we analyzed data from year 2003
      medical records of patients from 4 hospitals in Java (study 3). The average
      incidence of onychomycosis among fungal diseases increased to 4.7% in large
      cities that, from an average incidence within Indonesia of 3.5% in 1997-1998. At
      only 0.5%, the incidence of onychomycosis among all skin diseases was low in both
      study 1 and 3. Female patients outnumbered male patients with a ratio of 1.5:1 to
      2:1. In study 2, the fingernail was the site most frequently affected. KOH
      examinations and fungal culture in study 1 (n=557) showed causative organisms to
      be Candida (50.1%), dermatophytes (26.2%), moulds (3.1%) and mixed infections
      (1.8%), with the remainder (18.7%) unidentified. Similar frequency of causative
      organisms was reported in study 2 (n=113) and in study 3 (n=183). People's low
      awareness of nail disease and consequent lack of concern as well as the limited
      diagnostic ability of KOH examination and fungal culture might influence the low
      incidence of the disease and the frequency of detection of the causative
      organisms.

PMID- 16094292
TI  - [Evaluation of the efficacy of miconazole nitrate shampoo for prevention against
      T. tonsurans infection].
AB  - We report the efficacy of miconazole nitrate shampoo (Furfur Shampoo) to prevent
      T. tonsurans infection. METHOD: Experimental models were made from stratum
      corneum of healthy human heel or guinea pig skin. Before and/or after T.
      tonsurans was applied, samples were washed with miconazole nitrate shampoo, then
      inoculated on a Sabouraud culture plate. RESULT: Though miconazole nitrate
      shampoo did not eliminate T. tonsurans on the sample completely, the time
      required to develop the colony (9.9 days) was obviously extended (7.7 days by
      control). DISCUSSION: We concluded that miconazole nitrate shampoo is a useful
      method of preventing T. tonsurans infection, and should be used every day
      (before/after the chance to infect).

PMID- 16094293
TI  - [A case of dermal cutaneous alternariosis].
AB  - Alternaria is a saprophytic fungus that naturally subsists on decaying plant
      materials, but may be an opportunistic pathogen in immunocompromised hosts. We
      describe a case of dermal cutaneous alternariosis in a 70-year-old patient, who
      was on systemic steroid administration for autoimmune hemolytic anemia. The
      patient also had chronic heart failure, liver dysfunction, and diabetes mellitus.
      Infection was confirmed by histological examination, and multiple positive
      culture results. Treatment with oral terbinafine and itraconazole was
      ineffective. We review the literature of dermal cutaneous alternariosis reported
      in Japan; including our case, 15 cases have been reported. Recognition of
      Alternaria as a potential opportunistic pathogen is important for the
      differential diagnosis of dermatologic lesion, such as granulomatous lesion or
      ulcer, in immunocompromised hosts.

PMID- 16094294
TI  - Safe specimen preparation for electron microscopy of pathogenic fungi by freeze
      substitution after glutaraldehyde fixation.
AB  - A safe method is described for observing ultrastructure of highly infectious
      fungi by ultrathin sectioning electron microscopy. The fungal cells were first
      chemically fixed by glutaraldehyde to kill them. They were then rapidly frozen by
      propane slush in liquid nitrogen and freeze-substituted in acetone containing 2%
      osmium tetroxide. This method gave clear cell images with high resolution in a
      natural state, close to the image obtained by rapidly frozen freeze-substituted
      specimen of living cells. Although we have demonstrated the utility of this
      method using Exophiala dermatitidis and Cryptococcus neoformans, it could also be
      used for observing highly infectious fungi such as Coccidioides immitis.

PMID- 16094295
TI  - [Molecular analysis of Malassezia species isolated from three cases of Akatsuki
      disease (pomade crust)].
AB  - Malassezia spp. which normally colonize on the skin surface, are known as being
      either the cause or an exacerbating factor in a variety of skin conditions,
      including pityriasis versicolor, folliculitis, seborrheic dermatitis and atopic
      dermatitis. We report here three cases of Akatsuki disease (pomade crust). Scales
      and crusts were collected from the lesional skin and analyzed using a PCR-based
      non-culture method. Malassezia microflora in Akatsuki disease was compared to
      that of healthy subjects and atopic dermatitis patients. Samples were collected
      from upper and lower eyelids (Case 1), an operation scar (Case 2) and parietal
      scalp (Case 3). DNA was extracted from the scales and nested PCR was performed
      using specific primers for each species. Our analysis detected only M. obtusa and
      M. slooffiae in Cases 1 and 3 and only M. slooffiae in Case 2. Our previous data
      indicated that while M. globosa, M. restricta and M. sympodialis were common in
      healthy subjects, the two aforementioned species were rare, suggesting that the
      presence of M. obtusa and M. slooffiae in the subjects in the present study is
      correlated to the pathogenesis of Akatsuki disease.

PMID- 16094296
TI  - In vitro investigation of antifungal activities of phenotypic variation Candida
      albicans strains against fluconazole, itraconazole and voriconazole.
AB  - The aim of this study was to investigate the susceptibility of the different
      phenotypes of Candida albicans strains isolated from clinical specimens to three
      antifungal agents, fluconazole, itraconazole and voriconazole. Totally 215
      specimens were collected from oropharyngeal, gastrointestinal and urogenital
      tracts of non-neutropenic patients who had received no previous prophylactic
      treatment. Each of the 215 C. albicans strains recovered was found to express one
      of the six phenotypes: smooth 73%, fuzzy 10.7%, irregular 2.3%, star 2.8%, ring
      6% or stipple 5.1%. The mean MICs for the six phenotypes of C. albicans strains
      ranged between 0.25 microg/ml and 64 microg/ml for fluconazole, 0.03 microg/ml
      and 1 microg/ml for itraconazole and 0.03 microg/ml and 0.5 microg/ml for
      voriconazole. The mean minimum inhibitory concentration (MIC) of fluconazole was
      consistently higher for C. albicans strains expressing the stipple phenotype. The
      antifungal susceptibility of the phenotypic switching requires attention,
      especially in patients who are clinically unresponsive to fluconazole
      chemotherapy or in cases of serious C. albicans infections of immunocompromised
      hosts.

PMID- 16094297
TI  - No detectable genetic correlation between male and female mating frequency in the
      stalk-eyed fly Cyrtodiopsis dalmanni.
AB  - There is much interest in explaining why female insects mate multiply. Females of
      the stalk-eyed fly Cyrtodiopsis dalmanni can mate several times each day in a
      lifetime which may span several months. There are many adaptive explanations, but
      one hypothesis that has received little rigorous empirical attention is that
      female multiple mating has evolved for non-adaptive reasons as a correlated
      response to selection for high male mating frequency rather than because of
      direct or indirect benefits accruing to females. We tested this hypothesis in
      stalk-eyed flies by measuring the mating frequency of females from lines that
      exhibited a direct response in males to artificial selection for increased
      ('high') and decreased ('low') male mating frequency. We found that the mating
      frequency of high-line females did not differ from that of low-line females.
      Hence, there was no support for a genetic correlation between male and female
      mating frequency in this species. Our study suggests that the genes which
      influence remating may not be the same in the sexes, and that females remate
      frequently in this species to gain as yet unidentified benefits.

PMID- 16094298
TI  - Estimation of allele frequencies in polyploids under certain patterns of
      inheritance.
AB  - Allele frequencies have long been studied by biologists interested in evolution
      and speciation. More recently, with the application of molecular markers in human
      DNA profiling we have also seen the need for reliable population allele frequency
      estimates for making probabilistic inferences. There is now interest in applying
      the same DNA profiling technology to identification of plant varieties.
      HortResearch maintains a large germplasm of horticultural plant species. It is
      becoming evident that accurate identification of these accessions through DNA
      fingerprinting is essential for effective utilisation and maintenance of this
      germplasm. Microsatellites are the markers of choice for this fingerprinting.
      However, such markers do not reveal the dosage of alleles in a polyploid.
      Polyploidy is common amongst horticultural plants. Estimating allele frequencies
      in a polyploid population is, therefore, complicated because of some marker
      genotypes being phenotypically indistinguishable. For example, in a tetraploid,
      with four alleles at a locus showing polysomic inheritance, although 35 genotypes
      are possible, these will fall into only 15 marker phenotypic classes. Furthermore
      'null' individuals are rarely detected in polyploids. Furthermore, some
      polyploids can be cryptic exhibiting disomy, instead of the polysomic
      inheritance. We will discuss the implications of these factors and present an EM
      type algorithm for estimating allele frequencies of a polyploid population under
      certain patterns of inheritance. The method will be demonstrated on simulated
      data. We also discuss the nature of some of the additional problems that may be
      encountered with estimating allele frequencies in polyploids for which other
      solutions still need to be developed.

PMID- 16094299
TI  - Genetic structure of Indian scad mackerel Decapterus russelli: Pleistocene
      vicariance and secondary contact in the Central Indo-West Pacific Seas.
AB  - Major genetic breaks between the Indian and Pacific oceans have been reported for
      marine fishes and invertebrates. The genetic structure and history of the Indian
      scad mackerel, Decapterus russelli, in the Indo-Malay archipelago were
      investigated using the cytochrome b gene sequence as mitochondrial marker and two
      length-polymorphic introns as nuclear markers. The existence of two major
      mitochondrial lineages separated by 2.2% average nucleotide divergence, and their
      heterogeneous geographical distributions, were confirmed. This indicated past
      geographic isolation, possibly caused by a Pleistocene drop in sea level. The
      presence, in sympatry, of the two mitochondrial lineages was thought to result
      from secondary contact. A recent population bottleneck and subsequent rapid
      population expansion were indicated by low genetic diversities and strongly
      negative Tajima's D-values. This evidence supports the hypothesis that the
      habitat available to D. russelli in the Pleistocene was restricted. Taking into
      account both mitochondrial and nuclear-DNA data, three geographically distinct
      populations were identified: one sampled in the Makassar Strait and Sulawesi Sea,
      one in the Arafura Sea and the third from the entire western region of the Indo
      Malay archipelago. Considering the high hydrological connectivity of this region
      of the Indo-Pacific and the species pelagic life-history, the population
      structure may be maintained by homing behaviour and, perhaps, the association of
      spawning with retention zones.

PMID- 16094300
TI  - Genetic resource impacts of habitat loss and degradation; reconciling empirical
      evidence and predicted theory for neotropical trees.
AB  - The theoretical impacts of anthropogenic habitat degradation on genetic resources
      have been well articulated. Here we use a simulation approach to assess the
      magnitude of expected genetic change, and review 31 studies of 23 neotropical
      tree species to assess whether empirical case studies conform to theory. Major
      differences in the sensitivity of measures to detect the genetic health of
      degraded populations were obvious. Most studies employing genetic diversity (nine
      out of 13) found no significant consequences, yet most that assessed progeny
      inbreeding (six out of eight), reproductive output (seven out of 10) and fitness
      (all six) highlighted significant impacts. These observations are in line with
      theory, where inbreeding is observed immediately following impact, but genetic
      diversity is lost slowly over subsequent generations, which for trees may take
      decades. Studies also highlight the ecological, not just genetic, consequences of
      habitat degradation that can cause reduced seed set and progeny fitness.
      Unexpectedly, two studies examining pollen flow using paternity analysis
      highlight an extensive network of gene flow at smaller spatial scales (less than
      10 km). Gene flow can thus mitigate against loss of genetic diversity and assist
      in long-term population viability, even in degraded landscapes. Unfortunately,
      the surveyed studies were too few and heterogeneous to examine concepts of
      population size thresholds and genetic resilience in relation to life history.
      Future suggested research priorities include undertaking integrated studies on a
      range of species in the same landscapes; better documentation of the extent and
      duration of impact; and most importantly, combining neutral marker, pollination
      dynamics, ecological consequences, and progeny fitness assessment within single
      studies.

PMID- 16094301
TI  - The evolutionary ecology of the major histocompatibility complex.
AB  - The major histocompatibility complex (MHC) has become a paradigm for how
      selection can act to maintain adaptively important genetic diversity in natural
      populations. Here, we review the contribution of studies on the MHC in non-model
      species to our understanding of how selection affects MHC diversity, emphasising
      how ecological and ethological processes influence the tempo and mode of
      evolution at the MHC, and conversely, how variability at the MHC affects
      individual fitness, population dynamics and viability. We focus on three main
      areas: the types of information that have been used to detect the action of
      selection on MHC genes; the relative contributions of parasite-mediated and
      sexual selection on the maintenance of MHC diversity; and possible future lines
      of research that may help resolve some of the unanswered issues associated with
      MHC evolution.

PMID- 16094302
TI  - Distribution of genetic diversity among disjunct populations of the rare forest
      understory herb, Trillium reliquum.
AB  - We assessed genetic diversity and its distribution in the rare southeastern US
      forest understory species, Trillium reliquum. In all, 21 loci were polymorphic
      (PS=95.5%) and the mean number of alleles per polymorphic locus was 3.05.
      However, genetic diversity was relatively low (Hes=0.120) considering the level
      of polymorphism observed for this outcrossing species. A relatively high portion
      of the genetic diversity (29.7%) was distributed among populations. There was no
      relationship between population size and genetic diversity, and we did not detect
      significant inbreeding. These results are best explained by the apparent self
      incompatibility of this species, its longevity and clonal reproduction. To
      address questions regarding the history of T. reliquum's rarity, we compared
      results for T. reliquum with that of its more common and partially sympatric
      congener, T. cuneatum. Despite shared life history traits and history of land
      use, we observed significant genetic differences between the two species.
      Although T. cuneatum contains slightly lower polymorphism (Ps=85%), we detected
      significantly higher genetic diversity (Hes=0.217); most of its genetic diversity
      is contained within its populations (GST=0.092). Our results suggest that not
      only is there little gene flow among extant T. reliquum populations, but that
      rarity and population isolation in this species is of ancient origins, rather
      than due to more recent anthropogenic fragmentation following European
      colonization. The Chattahoochee River was identified as a major barrier to gene
      exchange.

PMID- 16094303
TI  - Spatial genetic structure of Simarouba amara Aubl. (Simaroubaceae), a dioecious,
      animal-dispersed Neotropical tree, on Barro Colorado Island, Panama.
AB  - Simarouba amara (Simaroubaceae) is a vertebrate-dispersed, insect-pollinated
      Neotropical tree found in lowland moist forest from upper Mesoamerica to the
      Amazon basin. We assessed the spatial genetic structure of S. amara within the 50
      ha Forest Dynamics Plot on Barro Colorado Island in the Republic of Panama. A
      total of 300 individuals were genotyped using five microsatellite loci,
      representing 100 individuals with a dbh>or=10 cm, 100 individuals of 1-10 cm dbh,
      and 100 individuals of <1 cm dbh. The 200 individuals in the two larger size
      classes were also genotyped with 155 AFLP loci. Spatial autocorrelation analysis
      using Moran's Index detected significant genotypic association at the smallest
      distance classes for 1-10 cm dbh (0-20 m) and >10 cm dbh (0-40 m) size
      categories. Significant spatial autocorrelations were detected over larger scales
      (0-140 m) in <1 cm dbh individuals. The relatively weak genetic structure of S.
      amara, in comparison to other recent studies, may be explained by pollen and seed
      dispersal over the 50 ha plot, overlapping seed shadows, and postrecruitment
      mortality.

PMID- 16094304
TI  - To self, or not to self... a review of outcrossing and pollen-mediated gene flow
      in neotropical trees.
AB  - Despite the typically low population densities and animal-mediated pollination of
      tropical forest trees, outcrossing and long-distance pollen dispersal are the
      norm. We reviewed the genetic literature on mating systems and pollen dispersal
      for neotropical trees to identify the ecological and phylogenetic correlates. The
      36 studies surveyed found >90% outcrossed mating for 45 hermaphroditic or
      monoecious species. Self-fertilization rates varied inversely with population
      density and showed phylogenetic and geographic trends. The few direct measures of
      pollen flow (N=11 studies) suggest that pollen dispersal is widespread among low
      density tropical trees, ranging from a mean of 200 m to over 19 km for species
      pollinated by small insects or bats. Future research needs to examine (1) the
      effect of inbreeding depression on observed outcrossing rates, (2) pollen
      dispersal in a wide range of pollination syndromes and ecological classes, (3)
      and the range of variation of mating system expression at different hierarchical
      levels, including individual, seasonal, population, ecological, landscape and
      range wide.

PMID- 16094305
TI  - Research network: EuroGentest--a European Network of Excellence aimed at
      harmonizing genetic testing services.

PMID- 16094306
TI  - Biological clock: biological clocks may modulate drug addiction.

PMID- 16094307
TI  - The place of the Basques in the European Y-chromosome diversity landscape.
AB  - There is a trend to consider the gene pool of the Basques as a 'living fossil' of
      the earliest modern humans that colonized Europe. To investigate this assumption,
      we have typed 45 binary markers and five short tandem repeat loci of the Y
      chromosome in a set of 168 male Basques. Results on these combined haplotypes
      were analyzed in the context of matching data belonging to approximately 3000
      individuals from over 20 European, Near East and North African populations, which
      were compiled from the literature. Our results place the low Y-chromosome
      diversity of Basques within the European diversity landscape. This low diversity
      seems to be the result of a lower effective population size maintained through
      generations. At least some lineages of Y chromosome in modern Basques originated
      and have been evolving since pre-Neolithic times. However, the strong genetic
      drift experienced by the Basques does not allow us to consider Basques either the
      only or the best representatives of the ancestral European gene pool. Contrary to
      previous suggestions, we do not observe any particular link between Basques and
      Celtic populations beyond that provided by the Paleolithic ancestry common to
      European populations, nor we find evidence supporting Basques as the focus of
      major population expansions.

PMID- 16094308
TI  - Demography: peopling the Americas.

PMID- 16094309
TI  - Variable expressivity of the clinical and biochemical phenotype associated with
      the apolipoprotein E p.Leu149del mutation.
AB  - Splenomegaly with sea-blue histiocytes, thrombocytopenia and hypertriglyceridemia
      is a very rare association that has been described in only one report to date.
      The molecular defect in the two reported patients consists in a deletion of a
      leucine at position 149 in the receptor-binding region of the apoE molecule.
      Here, we report on another family in whom the proband and his brother were
      diagnosed with splenomegaly, thrombocytopenia and hypertriglyceridemia. An apoE
      p.Leu149del mutation was found in both subjects. A large beta band in the VLDL
      fraction and elevated VLDL cholesterol-to-plasma triglyceride ratio was observed
      in the proband only. Their mother, presenting with isolated hypertriglyceridemia,
      also carried the same p.Leu149del mutation. The coexistence of factors
      facilitating the development of hypertriglyceridemia and/or low HDL-cholesterol
      level could explain why the proband and his brother developed a splenomegaly with
      thrombocytopenia, whereas the mother did not. Moreover, the presence of an apoE2
      allele in the proband likely explains the more severe phenotype we observed in
      this subject. In conclusion, the apoE p.Leu149del mutation results in a very
      striking phenotype including one or all symptoms among splenomegaly,
      thrombocytopenia and hypertriglyceridemia, and should be considered as a
      differential diagnosis of storage disorders in the causes of splenomegaly with
      sea-blue histiocytes.

PMID- 16094310
TI  - Essay: early American genetics journals.
AB  - Before the Second World War, there were only two North-American journals
      exclusively devoted to genetics - the Journal of Heredity and Genetics. In the
      late 1940s, Genetics spawned two progeny - the American Journal of Human Genetics
      and Evolution. This article recounts the early days of these journals, their
      influential and often colourful founding editors, and their contents. It
      emphasizes the contrast between those years, when a reader had a realistic chance
      of keeping up with the whole field, and the current plethora of journals that
      makes it impossible to keep up with even the tables of contents.

PMID- 16094311
TI  - The molecular elements that underlie developmental evolution.
AB  - Abundant evidence indicates that developmental evolution, the foundation of
      morphological evolution, is based on changes in gene function. Over the past
      decade a consensus has developed that transcriptional regulation, acting through
      enhancer sequences, is the primary level of evolutionarily significant change.
      Here we propose that other regulatory levels are probably as important as
      enhancers in developmental evolution. We also explain why these alternative
      regulatory levels might have been neglected, and briefly discuss ways to test our
      hypothesis.

PMID- 16094312
TI  - Replication and transcription: shaping the landscape of the genome.
AB  - As the relationship between nuclear structure and function begins to unfold, a
      picture is emerging of a dynamic landscape that is centred on the two main
      processes that execute the regulated use and propagation of the genome. Rather
      than being subservient enzymatic activities, the replication and transcriptional
      machineries provide potent forces that organize the genome in three-dimensional
      nuclear space. Their activities provide opportunities for epigenetic changes that
      are required for differentiation and development. In addition, they impose
      physical constraints on the genome that might help to shape its evolution.

PMID- 16094315
TI  - Rat neonatal immune challenge alters adult responses to cerebral ischaemia.
AB  - Infection, inflammation, and hyperthermia associated with cerebral ischaemia are
      known to contribute to enhanced neuronal cell loss and more severe behavioural
      deficits. Because neonatal exposure to an immune challenge has been shown to
      alter the severity of inflammatory and febrile responses to a further immune
      challenge experienced in adulthood, we hypothesised that this could also alter
      temperature responses and neuronal survival after ischaemia. Thus, male Sprague
      Dawley rats were treated at postnatal day 14 with a single injection of the
      bacterial endotoxin lipopolysaccharide (LPS) and were examined as adults for
      temperature changes, behavioural deficits, and neuronal cell loss associated with
      global cerebral ischaemia after a two-vessel occlusion (2VO). Neonatally LPS
      treated rats showed behavioural differences in a novel object exploration
      paradigm, as well as altered temperature responses to the 2VO compared with
      neonatally saline-treated controls. Interestingly, these neonatally LPS-treated
      rats also showed increased cell loss in the central nucleus of the amygdala, a
      region that is important in the processing of emotional responses, but that is
      not usually examined in animal models of cerebral ischaemia. No differences were
      seen in the CA1, CA3, or dentate gyrus regions of the hippocampus. This work
      shows the importance of examining brain regions other than the hippocampus in
      association with global ischaemia. We also highlight the importance of the early
      period of development in programming an animal's ability to deal with injury such
      as cerebral ischaemia in adulthood.

PMID- 16094314
TI  - CuZn-SOD deficiency, rather than overexpression, is associated with enhanced
      recovery and attenuated activation of NF-kappaB after brain trauma in mice.
AB  - Superoxide-dismutases (SOD) catalyze O2- conversion to hydrogen peroxide (H2O2)
      and with other antioxidant enzymes and low molecular weight antioxidants (LMWA)
      constitute endogenous defense mechanisms. We first assessed the effects of SOD1
      levels on outcome after closed head injury (CHI) and later, based on these
      results, the effects of SOD1 deficiency on cellular redox homeostasis. Superoxide
      dismutase 1-deficient (SOD1-/-) and -overexpressing (transgenic (Tg)) mice and
      matched wild-type (WT) controls were subjected to CHI and outcome
      (neurobehavioral and memory functions) was assessed during 14 days. Brain edema,
      LMWA, and SOD2 activity were measured along with histopathological analysis.
      Transactivation of nuclear factor-kappa B (NF-kappaB) was evaluated by
      electromobility shift assay. Mortality, motor, and cognitive outcome of Tg and WT
      mice were comparable. Mortality and edema were similar in SOD1-/- and WT mice,
      yet, unexpectedly, SOD1-/- displayed better neurobehavioral recovery (P<0.05) at
      14 days after CHI. Basal LMWA were higher in the cortex and liver of SOD1-/- mice
      (P<0.05) and similar to WT in the cerebellum. Five minutes after CHI, cortical
      LMWA decreased only in SOD1-/- mice. One week after CHI, SOD2 activity decreased
      fourfold in WT cortex (P<0.001), but was preserved in the SOD1-/-. Constitutive
      NF-kappaB transactivation was comparably low in SOD1-/- and WT; however, CHI
      induced a robust NF-kappaB activation that was absent in SOD1-/- cortices
      (P<0.005 versus WT). At the same time, immunohistochemical analysis of brain
      sections revealed that astrogliosis and neurodegeneration were of lesser severity
      in SOD1-/- mice. We suggest that SOD1 deficiency impairs H2O2-mediated activation
      of NF-kappaB, decreasing death-promoting signals, and leading to better outcome.

PMID- 16094313
TI  - Estradiol alters only GAD67 mRNA levels in ischemic rat brain with no consequent
      effects on GABA.
AB  - The present study tested the hypothesis that estradiol reduces tissue infarction
      after middle cerebral artery occlusion (MCAO) in estradiol-deficient females by
      augmenting glutamic acid decarboxylase (GAD) expression and thus activity,
      leading to increases in gamma-amino-butyric acid (GABA) tissue levels. Glutamic
      acid decarboxylase is the principal enzyme for GABA synthesis and has two
      isoforms, GAD65 and GAD67, which differ in size and cellular distribution. Rats
      were ovariectomized 7 to 8 days before receiving no hormone, placebo, or 25
      microg estradiol via subcutaneous implant 7 to 10 days before harvesting tissue
      in either ischemic cohorts after 2 h of MCAO (end-ischemia) or in nonischemic
      cohorts. Selected cortical and striatal regions were microdissected from
      harvested brains. GAD65/67 mRNA levels were determined by microlysate
      ribonuclease protection assay. End-ischemic GABA concentrations were determined
      by HPLC. Steroid treatment selectively decreased ischemic cortical GAD67 mRNA
      levels. In most brain regions evaluated, regional GABA concentrations increased
      with ischemia regardless of treatment. Estradiol blocked MCAO-induced increases
      in GABA concentration only in dorsomedial cortex. These data suggest that
      estradiol repletion in ischemic rat brain selectively decreases GAD67 mRNA levels
      but does not alter steady-state GABA concentrations. It may be that estradiol
      under ischemic conditions is attenuating GABA metabolism rather than enhancing
      synthesis or is augmenting other aspects of GABAergic transmission such as GABA
      transporters and receptors.

PMID- 16094316
TI  - Induction of prostacyclin/PGI2 synthase expression after cerebral ischemia
      reperfusion.
AB  - Prostacyclin (PGI2), a potent vasodilator and inhibitor of platelet aggregation
      and leukocyte activation, is crucial in vascular diseases such as stroke.
      Prostacyclin synthase (PGIS) is the key enzyme for PGI2 synthesis. Although
      expression of PGIS was noted in the brain, its role in ischemic insult remains
      unclear. Here we reported the temporal and spatial expression of PGIS mRNA and
      protein after 60-min transient ischemia. Northern blot and in situ hybridization
      revealed a delayed increase of PGIS mRNA in the ischemic cortex at 24- to 72-h
      after ischemia; PGIS was detected mainly in the ipsilateral penumbra area,
      pyriform cortex, hippocampus, and leptomeninges. Western blot and
      immunohistochemical analysis revealed that PGIS proteins were expressed
      temporally and spatially similar to PGIS mRNA. PGIS was heavily colocalized with
      PECAM-1 to endothelial cells at the leptomeninges, large and small vessels, and
      localized to neuronal cells, largely at the penumbra area. A substantial amount
      of PGIS was also detected in the macrophage and glial cells. To evaluate its role
      against ischemic infarct, we overexpressed PGIS by adenoviral gene transfer. When
      infused 72 h before ischemia (- 72 h), Adv-PGIS reduced infarct volume by
      approximately 50%. However, it had no effect on infarct volume when infused
      immediately after ischemia (0 h). Eicosanoid analysis revealed selective
      elevation of PGI2 at - 72 h while PGI2 and TXB2 were both elevated at 0 h,
      altering the PGI2/thromboxane A2 (TXA2) ratio from 10 to 4. These findings
      indicate that PGIS protects the brain by enhancing PGI2 synthesis and creating a
      favorable PGI2/TXA2 ratio.

PMID- 16094317
TI  - Cerebral vascular effects of angiotensin II: new insights from genetic models.
AB  - Very little is known regarding the mechanisms of action of angiotensin II (Ang
      II) or the consequences of Ang II-dependent hypertension in the cerebral
      circulation. We tested the hypothesis that Ang II produces constriction of
      cerebral arteries that is mediated by activation of AT1A receptors and Rho
      kinase. Basilar arteries (baseline diameter approximately 130 microm) from mice
      were isolated, cannulated and pressurized to measure the vessel diameter.
      Angiotensin II was a potent constrictor in arteries from male, but not female,
      mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho
      kinase (Y-27632) in control mice, and was reduced by approximately 85% in mice
      deficient in expression of AT1A receptors. We also examined the chronic effects
      of Ang II using a model of Ang II-dependent hypertension, mice which overexpress
      human renin (R+) and angiotensinogen (A+). Responses to the endothelium-dependent
      agonist acetylcholine were markedly impaired in R+A+ mice (P<0.01) compared with
      controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A
      23187 (another endothelium-dependent agonist) produced vasodilation in control
      mice, but no response or vasoconstriction in R+A+ mice. In contrast, dilation of
      the basilar artery in response to a NO donor (NONOate) was similar in R+A+ mice
      and controls. Thus, Ang II produces potent constriction of cerebral arteries via
      activation of AT1A receptors and Rho-kinase. There are marked gender differences
      in cerebral vascular responses to Ang II. Endothelial function is greatly
      impaired in a genetic model of Ang II-dependent hypertension via a mechanism that
      involves superoxide.

PMID- 16094318
TI  - Imaging visual recognition memory network by PET in the baboon: perirhinal cortex
      heterogeneity and plasticity after perirhinal lesion.
AB  - We recently mapped the visual recognition memory network in the behaving baboon
      using a positron emission tomography (PET) activation paradigm with 18F-fluoro
      deoxyglucose during a visual delayed matching-to-sample task. This study
      confirmed the key role of the perirhinal cortex and documented an unexpected left
      sided advantage. Specific contribution of each subdivision of the perirhinal
      cortex has, however, never been investigated. Furthermore, although alteration to
      the perirhinal cortex has been implicated in several brain disorders, putative
      plasticity within the entire brain network after perirhinal damage remains
      largely unknown. To confirm our previous data and to investigate these latter
      issues, we used our PET activation paradigm on a second healthy baboon before and
      after 16 months after bilateral excitotoxic lesions of the perirhinal cortex.
      Activation common to our two healthy baboons occurred only in the left
      rostroventral perirhinal cortex (i.e., areas 36pm and rostral 36r) and insular
      cortex. Although histologic analysis disclosed that the perirhinal lesions
      achieved in the present baboon were essentially caudal to this preoperatively
      activated area, memory performance was severely impaired. Concomitant with this
      long-lasting cognitive deficit, changes in the neural network implicated in the
      task were observed, involving disappearance of the preoperative activations and
      appearance of a significant activation of the frontal and occipital cortices.
      However, different activation patterns were found in the first and last eight
      postoperative months. These findings highlight the functional heterogeneity of
      the perirhinal cortex and evidence progressive plasticity after perirhinal cortex
      damage.

PMID- 16094319
TI  - Increased infarct size and lack of hyperphagic response after focal cerebral
      ischemia in peroxisome proliferator-activated receptor beta-deficient mice.
AB  - Peroxisome proliferator-activated receptors (PPARs) are involved in energy
      expenditure, regulation of inflammatory processes, and cellular protection in
      peripheral tissues. Among the different types of PPARs, PPARbeta is the only one
      to be widely expressed in cortical neurons. Using PPARbeta knockout (KO) mice, we
      report here a detailed investigation of the role of PPARbeta in cerebral ischemic
      damage, associated inflammatory and antioxidant processes as well as food intake
      regulation after middle cerebral artery occlusion (MCAO). The PPARbeta KO mice
      had a two-fold increase in infarct size compared with wild-type (WT) mice. Brain
      oxidative stress was dramatically enhanced in these KO mice, as documented by an
      increased content of malondialdehyde, decreased levels of glutathione and
      manganese superoxide dismutase, and no induction of uncoupling protein 2 (UCP2)
      mRNA. Unlike WT mice, PPARbeta KO mice showed a marked increase of prooxidant
      interferon-gamma but no induction of nerve growth factor and tumor necrosis
      factor alpha after MCAO. In WT mice, MCAO resulted in inflammation-specific
      transient hyperphagia from day 3 to day 5 after ischemia, which was associated
      with an increase in neuropeptide Y (NPY) mRNA. This hyperphagic phase and NPY
      mRNA induction were not observed in PPARbeta KO mice. Furthermore, our study also
      suggests for the first time that UCP2 is involved in MCAO food intake response.
      These data indicate that PPARbeta plays an important role in integrating and
      regulating central inflammation, antioxidant mechanisms, and food intake after
      MCAO, and suggest that the use of PPARbeta agonists may be of interest for the
      prevention of central ischemic damage.

PMID- 16094320
TI  - Parkinson's disease and brain mitochondrial dysfunction: a functional phosphorus
      magnetic resonance spectroscopy study.
AB  - In spite of several evidences for a mitochondrial impairment in Parkinson's
      disease (PD), so far it has not been possible to show in vivo mitochondrial
      dysfunction in the human brain of PD patients. The authors used the high temporal
      and spatial resolution 31 phosphorus magnetic resonance spectroscopy (31P MRS)
      technique, which they have previously developed in normal subjects and in
      patients with mitochondrial diseases to study mitochondrial function by observing
      high-energy phosphates (HEPs) and intracellular pH (pH) in the visual cortex of
      20 patients with PD and 20 normal subjects at rest, during, and after visual
      activation. In normal subjects, HEPs remained unchanged during activation, but
      rose significantly (by 16%) during recovery, and pH increased during visual
      activation with a slow return to rest values. In PD patients, HEPs were within
      the normal range at rest and did not change during activation, but fell
      significantly (by 36%) in the recovery period; pH did not reveal a homogeneous
      pattern with a wide spread of values. Energy unbalance under increased oxidative
      metabolism requirements, that is, the postactivation phase, discloses a
      mitochondrial dysfunction that is present in the brain of patients with PD even
      in the absence of overt clinical manifestations, as in the visual cortex. This is
      in agreement with our previous findings in patients with mitochondrial disease
      without clinical central nervous system (CNS) involvement. The heterogeneity of
      the physicochemical environment (i.e., pH) suggests various degrees of
      subclinical brain involvement in PD. The combined use of MRS and brain activation
      is fundamental for the study of brain energetics in patients with PD and may
      prove an important tool for diagnostic purposes and, possibly, to monitor
      therapeutic interventions.

PMID- 16094322
TI  - Life in the old doc yet.

PMID- 16094323
TI  - Keeping religion out of science class.

PMID- 16094324
TI  - Tale of two tigers.

PMID- 16094321
TI  - Asymmetric cell divisions promote stratification and differentiation of mammalian
      skin.
AB  - The epidermis is a stratified squamous epithelium forming the barrier that
      excludes harmful microbes and retains body fluids. To perform these functions,
      proliferative basal cells in the innermost layer periodically detach from an
      underlying basement membrane of extracellular matrix, move outward and eventually
      die. Once suprabasal, cells stop dividing and enter a differentiation programme
      to form the barrier. The mechanism of stratification is poorly understood.
      Although studies in vitro have led to the view that stratification occurs through
      the delamination and subsequent movement of epidermal cells, most culture
      conditions favour keratinocytes that lack the polarity and cuboidal morphology of
      basal keratinocytes in tissue. These features could be important in considering
      an alternative mechanism, that stratification occurs through asymmetric cell
      divisions in which the mitotic spindle orients perpendicularly to the basement
      membrane. Here we show that basal epidermal cells use their polarity to divide
      asymmetrically, generating a committed suprabasal cell and a proliferative basal
      cell. We further demonstrate that integrins and cadherins are essential for the
      apical localization of atypical protein kinase C, the Par3-LGN-Inscuteable
      complex and NuMA-dynactin to align the spindle.

PMID- 16094326
TI  - Medics braced for fresh superbug.

PMID- 16094327
TI  - Scans provide picture of brain activity.

PMID- 16094328
TI  - Preparations get under way for tsunami warning system.

PMID- 16094329
TI  - Four years on, no transgenes found in Mexican maize.

PMID- 16094330
TI  - Scientists attack Bush over intelligent design.

PMID- 16094331
TI  - Japan accelerates global supercomputer war.

PMID- 16094332
TI  - Anti-terror study tracks gas dispersal.

PMID- 16094333
TI  - Europe set for tough debate on curbing aircraft emissions.

PMID- 16094337
TI  - Singapore: an irresistible force.

PMID- 16094338
TI  - Cell biology: the secret life of sperm.

PMID- 16094339
TI  - Science after retirement age: breaking the age barrier.

PMID- 16094341
TI  - Ancient foil maker wraps up mobile-phone market.

PMID- 16094343
TI  - Misconduct: acceptable practices differ by field.

PMID- 16094344
TI  - Tunnel vision all in the mind at Hothouse High.

PMID- 16094345
TI  - Harry Potter and the recessive allele.

PMID- 16094351
TI  - Magnetospheric physics: turbulence on a small scale.

PMID- 16094350
TI  - Neuroscience: neurons and navigation.

PMID- 16094352
TI  - Plant biology: engineered male sterility.

PMID- 16094354
TI  - Oceanography: a bigger nitrogen fix.

PMID- 16094355
TI  - Cancer: two in one.

PMID- 16094356
TI  - Mantle geochemistry: big lessons from little droplets.

PMID- 16094357
TI  - Organic chemistry: Dotty solutions.

PMID- 16094358
TI  - Phytochemistry: structure of the blue cornflower pigment.
AB  - The same anthocyanin pigment makes roses red but cornflowers blue, a phenomenon
      that has so far not been entirely explained. Here we describe the X-ray crystal
      structure of the cornflower pigment, which reveals that its blue colour arises
      from a complex of six molecules each of anthocyanin and flavone, with one ferric
      iron, one magnesium and two calcium ions. We believe that this tetrametal complex
      may represent a previously undiscovered type of supermolecular pigment.

PMID- 16094359
TI  - Colorectal cancer: mutations in a signalling pathway.
AB  - Protein kinases are enzymes that are important for controlling cellular growth
      and invasion, and their malfunction is implicated in the development of some
      tumours. We analysed human colorectal cancers for genetic mutations in 340
      serine/threonine kinases and found mutations in eight genes, including in three
      members of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway. The discovery
      of this mutational activation of a key cell-signalling pathway may provide new
      targets for therapeutic intervention.

PMID- 16094361
TI  - A dark jet dominates the power output of the stellar black hole Cygnus X-1.
AB  - Black holes undergoing accretion are thought to emit the bulk of their power in
      the X-ray band by releasing the gravitational potential energy of the infalling
      matter. At the same time, they are capable of producing highly collimated jets of
      energy and particles flowing out of the system with relativistic velocities. Here
      we show that the 10-solar-mass (10M(o)) black hole in the X-ray binary Cygnus X-1
      (refs 3-5) is surrounded by a large-scale (approximately 5 pc in diameter) ring
      like structure that appears to be inflated by the inner radio jet. We estimate
      that in order to sustain the observed emission of the ring, the jet of Cygnus X-1
      has to carry a kinetic power that can be as high as the bolometric X-ray
      luminosity of the binary system. This result may imply that low-luminosity
      stellar-mass black holes as a whole dissipate the bulk of the liberated accretion
      power in the form of 'dark', radiatively inefficient relativistic outflows,
      rather than locally in the X-ray-emitting inflow.

PMID- 16094360
TI  - Evasion of the p53 tumour surveillance network by tumour-derived MYC mutants.
AB  - The c-Myc oncoprotein promotes proliferation and apoptosis, such that mutations
      that disable apoptotic programmes often cooperate with MYC during tumorigenesis.
      Here we report that two common mutant MYC alleles derived from human Burkitt's
      lymphoma uncouple proliferation from apoptosis and, as a result, are more
      effective than wild-type MYC at promoting B cell lymphomagenesis in mice. Mutant
      MYC proteins retain their ability to stimulate proliferation and activate p53,
      but are defective at promoting apoptosis due to a failure to induce the BH3-only
      protein Bim (a member of the B cell lymphoma 2 (Bcl2) family) and effectively
      inhibit Bcl2. Disruption of apoptosis through enforced expression of Bcl2, or
      loss of either Bim or p53 function, enables wild-type MYC to produce lymphomas as
      efficiently as mutant MYC. These data show how parallel apoptotic pathways act
      together to suppress MYC-induced transformation, and how mutant MYC proteins, by
      selectively disabling a p53-independent pathway, enable tumour cells to evade p53
      action during lymphomagenesis.

PMID- 16094362
TI  - Discovery of the triple asteroidal system 87 Sylvia.
AB  - After decades of speculation, the existence of binary asteroids has been
      observationally confirmed, with examples in all minor planet populations.
      However, no triple systems have hitherto been discovered. Here we report the
      unambiguous detection of a triple asteroidal system in the main belt, composed of
      a 280-km primary (87 Sylvia) and two small moonlets orbiting at 710 and 1,360 km.
      We estimate their orbital elements and use them to refine the shape of the
      primary body. Both orbits are equatorial, circular and prograde, suggesting a
      common origin. Using the orbital information to estimate its mass and density, 87
      Sylvia appears to have a rubble-pile structure with a porosity of 25-60 per cent.
      The system was most probably formed through the disruptive collision of a parent
      asteroid, with the new primary resulting from accretion of fragments, while the
      moonlets are formed from the debris, as has been predicted previously.

PMID- 16094363
TI  - In situ multi-satellite detection of coherent vortices as a manifestation of
      Alfvenic turbulence.
AB  - Turbulence in fluids and plasmas is a ubiquitous phenomenon driven by a variety
      of sources-currents, sheared flows, gradients in density and temperature, and so
      on. Turbulence involves fluctuations of physical properties on many different
      scales, which interact nonlinearly to produce self-organized structures in the
      form of vortices. Vortex motion in fluids and magnetized plasmas is typically
      governed by nonlinear equations, examples of which include the Navier-Stokes
      equation, the Charney-Hasegawa-Mima equations and their numerous generalizations.
      These nonlinear equations admit solutions in the form of different types of
      vortices that are frequently observed in a variety of contexts: in atmospheres,
      in oceans and planetary systems, in the heliosphere, in the Earth's ionosphere
      and magnetosphere, and in laboratory plasma experiments. Here we report the
      discovery by the Cluster satellites of a distinct class of vortex motion-short
      scale drift-kinetic Alfven (DKA) vortices-in the Earth's magnetospheric cusp
      region. As is the case for the larger Kelvin-Helmholtz vortices observed
      previously, these dynamic structures should provide a channel for transporting
      plasma particles and energy through the magnetospheric boundary layers.

PMID- 16094364
TI  - Negative lattice expansion from the superconductivity--antiferromagnetism
      crossover in ruthenium copper oxides.
AB  - The mechanism of high-transition-temperature (high-T(c)) superconductivity in
      doped copper oxides is an enduring problem. Antiferromagnetism is established as
      the competing order, but the relationship between the two states in the
      intervening 'pseudogap' regime has become a central puzzle. The role of the
      crystal lattice, which is important in conventional superconductors, also remains
      unclear. Here we report an anomalous increase of the distance between copper
      oxide planes on cooling, which results in negative thermal volume expansion, for
      layered ruthenium copper oxides that have been doped to the boundary of
      antiferromagnetism and superconductivity. We propose that a crossover between
      these states is driven by spin ordering in the ruthenium oxide layers, revealing
      a novel mechanism for negative lattice expansion in solids. The differences in
      volume and lattice strain between the distinct superconducting and
      antiferromagnetic states can account for the phase segregation phenomena found
      extensively in low-doped copper oxides, and show that Cooper pair formation is
      coupled to the lattice. Unusually large variations of resistivity with magnetic
      field are found in these ruthenium copper oxides at low temperatures through
      coupling between the ordered Ru and Cu spins.

PMID- 16094365
TI  - A late Eemian aridity pulse in central Europe during the last glacial inception.
AB  - Investigating the processes that led to the end of the last interglacial period
      is relevant for understanding how our ongoing interglacial will end, which has
      been a matter of much debate (see, for example, refs 1, 2). A recent ice core
      from Greenland demonstrates climate cooling from 122,000 years ago driven by
      orbitally controlled insolation, with glacial inception at 118,000 years ago.
      Here we present an annually resolved, layer-counted record of varve thickness,
      quartz grain size and pollen assemblages from a maar lake in the Eifel (Germany),
      which documents a late Eemian aridity pulse lasting 468 years with dust storms,
      aridity, bushfire and a decline of thermophilous trees at the time of glacial
      inception. We interpret the decrease in both precipitation and temperature as an
      indication of a close link of this extreme climate event to a sudden southward
      shift of the position of the North Atlantic drift, the ocean current that brings
      warm surface waters to the northern European region. The late Eemian aridity
      pulse occurred at a 65 degrees N July insolation of 416 W m(-2), close to today's
      value of 428 W m(-2) (ref. 9), and may therefore be relevant for the
      interpretation of present-day climate variability.

PMID- 16094366
TI  - A wide depth distribution of seismic tremors along the northern Cascadia margin.
AB  - The Cascadia subduction zone is thought to be capable of generating major
      earthquakes with moment magnitude as large as M(w) = 9 at an interval of several
      hundred years. The seismogenic portion of the plate interface is mostly offshore
      and is currently locked, as inferred from geodetic data. However, episodic
      surface displacements-in the direction opposite to the long-term deformation
      motions caused by relative plate convergence across a locked interface-are
      observed about every 14 months with an unusual tremor-like seismic signature.
      Here we show that these tremors are distributed over a depth range exceeding 40
      km within a limited horizontal band. Many occurred within or close to the strong
      seismic reflectors above the plate interface where local earthquakes are absent,
      suggesting that the seismogenic process for tremors is fluid-related. The
      observed depth range implies that tremors could be associated with the variation
      of stress field induced by a transient slip along the deeper portion of the
      Cascadia interface or, alternatively, that episodic slip is more diffuse than
      originally suggested.

PMID- 16094367
TI  - The hangover gene defines a stress pathway required for ethanol tolerance
      development.
AB  - Repeated alcohol consumption leads to the development of tolerance, simply
      defined as an acquired resistance to the physiological and behavioural effects of
      the drug. This tolerance allows increased alcohol consumption, which over time
      leads to physical dependence and possibly addiction. Previous studies have shown
      that Drosophila develop ethanol tolerance, with kinetics of acquisition and
      dissipation that mimic those seen in mammals. This tolerance requires the
      catecholamine octopamine, the functional analogue of mammalian noradrenaline.
      Here we describe a new gene, hangover, which is required for normal development
      of ethanol tolerance. hangover flies are also defective in responses to
      environmental stressors, such as heat and the free-radical-generating agent
      paraquat. Using genetic epistasis tests, we show that ethanol tolerance in
      Drosophila relies on two distinct molecular pathways: a cellular stress pathway
      defined by hangover, and a parallel pathway requiring octopamine. hangover
      encodes a large nuclear zinc-finger protein, suggesting a role in nucleic acid
      binding. There is growing recognition that stress, at both the cellular and
      systemic levels, contributes to drug- and addiction-related behaviours in
      mammals. Our studies suggest that this role may be conserved across evolution.

PMID- 16094368
TI  - Small vertical movement of a K+ channel voltage sensor measured with luminescence
      energy transfer.
AB  - Voltage-gated ion channels open and close in response to voltage changes across
      electrically excitable cell membranes. Voltage-gated potassium (Kv) channels are
      homotetramers with each subunit constructed from six transmembrane segments, S1
      S6 (ref. 2). The voltage-sensing domain (segments S1-S4) contains charged
      arginine residues on S4 that move across the membrane electric field, modulating
      channel open probability. Understanding the physical movements of this voltage
      sensor is of fundamental importance and is the subject of controversy. Recently,
      the crystal structure of the KvAP channel motivated an unconventional 'paddle
      model' of S4 charge movement, indicating that the segments S3b and S4 might move
      as a unit through the lipid bilayer with a large (15-20-A) transmembrane
      displacement. Here we show that the voltage-sensor segments do not undergo
      significant transmembrane translation. We tested the movement of these segments
      in functional Shaker K+ channels by using luminescence resonance energy transfer
      to measure distances between the voltage sensors and a pore-bound scorpion toxin.
      Our results are consistent with a 2-A vertical displacement of S4, not the large
      excursion predicted by the paddle model. This small movement supports an
      alternative model in which the protein shapes the electric field profile,
      focusing it across a narrow region of S4 (ref. 6).

PMID- 16094369
TI  - Gating charge displacement in voltage-gated ion channels involves limited
      transmembrane movement.
AB  - Voltage-gated ion channels are responsible for generating electrical impulses in
      nerves and other excitable cells. The fourth transmembrane helix (S4) in voltage
      gated channels is the primary voltage-sensing unit that mediates the response to
      a changing membrane electric field. The molecular mechanism of voltage sensing,
      particularly with respect to the magnitude of the transmembrane movement of S4,
      remains controversial. To determine the extent of this transmembrane movement, we
      use fluorescent resonance energy transfer between the S4 domain and a reference
      point in the lipid bilayer. The lipophilic ion dipicrylamine distributes on
      either side of the lipid bilayer depending on the membrane potential, and is used
      here as a resonance-energy-transfer acceptor from donor molecules attached to
      several positions in the Shaker K+ channel. A voltage-driven transmembrane
      movement of the donor should produce a transient fluorescence change because the
      acceptor also translocates as a function of voltage. In Shaker K+ channels no
      such transient fluorescence is observed, indicating that the S4 segment does not
      translocate across the lipid bilayer. Based on these observations, we propose a
      molecular model of voltage gating that can account for the observed 13e gating
      charge with limited transmembrane S4 movement.

PMID- 16094370
TI  - Voltage-sensor activation with a tarantula toxin as cargo.
AB  - The opening and closing of voltage-activated Na+, Ca2+ and K+ (Kv) channels
      underlies electrical and chemical signalling throughout biology, yet the
      structural basis of voltage sensing is unknown. Hanatoxin is a tarantula toxin
      that inhibits Kv channels by binding to voltage-sensor paddles, crucial helix
      turn-helix motifs within the voltage-sensing domains that are composed of S3b and
      S4 helices. The active surface of the toxin is amphipathic, and related toxins
      have been shown to partition into membranes, raising the possibility that the
      toxin is concentrated in the membrane and interacts only weakly and transiently
      with the voltage sensors. Here we examine the kinetics and state dependence of
      the toxin-channel interaction and the physical location of the toxin in the
      membrane. We find that hanatoxin forms a strong and stable complex with the
      voltage sensors, far outlasting fluctuations of the voltage sensors between
      resting (closed) conformations at negative voltages and activated (open)
      conformations at positive voltages. Toxin affinity is reduced by voltage-sensor
      activation, explaining why the toxin stabilizes the resting conformation. We also
      find that when hanatoxin partitions into membranes it is localized to an
      interfacial region, with Trp 30 positioned about 8.5 A from the centre of the
      bilayer. These results demonstrate that voltage-sensor paddles activate with a
      toxin as cargo, and suggest that the paddles traverse no more than the outer half
      of the bilayer during activation.

PMID- 16094371
TI  - Predictive models of molecular machines involved in Caenorhabditis elegans early
      embryogenesis.
AB  - Although numerous fundamental aspects of development have been uncovered through
      the study of individual genes and proteins, system-level models are still missing
      for most developmental processes. The first two cell divisions of Caenorhabditis
      elegans embryogenesis constitute an ideal test bed for a system-level approach.
      Early embryogenesis, including processes such as cell division and establishment
      of cellular polarity, is readily amenable to large-scale functional analysis. A
      first step toward a system-level understanding is to provide 'first-draft' models
      both of the molecular assemblies involved and of the functional connections
      between them. Here we show that such models can be derived from an integrated
      gene/protein network generated from three different types of functional
      relationship: protein interaction, expression profiling similarity and phenotypic
      profiling similarity, as estimated from detailed early embryonic RNA interference
      phenotypes systematically recorded for hundreds of early embryogenesis genes. The
      topology of the integrated network suggests that C. elegans early embryogenesis
      is achieved through coordination of a limited set of molecular machines. We
      assessed the overall predictive value of such molecular machine models by dynamic
      localization of ten previously uncharacterized proteins within the living embryo.

PMID- 16094372
TI  - Identification of JAK/STAT signalling components by genome-wide RNA interference.
AB  - Signalling pathways mediating the transduction of information between cells are
      essential for development, cellular differentiation and homeostasis. Their
      dysregulation is also frequently associated with human malignancies. The Janus
      tyrosine kinase/signal transducer and activator of transcription (JAK/STAT)
      pathway represents one such signalling cascade whose evolutionarily conserved
      roles include cell proliferation and haematopoiesis. Here we describe a
      systematic genome-wide survey for genes required for JAK/STAT pathway activity.
      Analysis of 20,026 RNA interference (RNAi)-induced phenotypes in cultured
      Drosophila melanogaster haemocyte-like cells identified interacting genes
      encoding 4 known and 86 previously uncharacterized proteins. Subsequently, cell
      based epistasis experiments were used to classify these proteins on the basis of
      their interaction with known components of the signalling cascade. In addition to
      multiple human disease gene homologues, we have found the tyrosine phosphatase
      Ptp61F and the Drosophila homologue of BRWD3, a bromo-domain-containing protein
      disrupted in leukaemia. Moreover, in vivo analysis demonstrates that disrupted
      dBRWD3 and overexpressed Ptp61F function as suppressors of leukaemia-like blood
      cell tumours. This screen represents a comprehensive identification of novel loci
      required for JAK/STAT signalling and provides molecular insights into an
      important pathway relevant for human cancer. Human homologues of identified
      pathway modifiers may constitute targets for therapeutic interventions.

PMID- 16094378
TI  - An application of peer-to-peer technology to the discovery, use and assessment of
      bioinformatics programs.

PMID- 16094379
TI  - EGASP: collaboration through competition to find human genes.
AB  - According to the most recent estimates, the number of human genes is possibly-
      but not certainly--between 20,000 and 25,000. To contribute strategies to reduce
      this uncertainty, several groups working on computational gene prediction met
      recently at the Welcome Trust Sanger Institute with the goal to test and compare
      predictive methods of genome annotation.

PMID- 16094380
TI  - A polymeric solution for enriching the phosphoproteome.

PMID- 16094381
TI  - Insect transgenesis by site-specific recombination.

PMID- 16094382
TI  - Site-specific transgenesis by Cre-mediated recombination in Drosophila.
AB  - Transposons such as P elements are routinely used to stably transfer exogenous
      DNA (transgenes) into the Drosophila genome. Transgene insertion events, however,
      are essentially random and are subject to 'position effects' from nearby
      endogenous regulatory elements. Here we describe a microinjection-based system
      that uses Cre-mediated recombination to insert transgenes into precise genomic
      'landing sites'. The system is simple and efficient, and will permit precise
      comparisons between multiple transgenic constructs.

PMID- 16094383
TI  - Multiplexed absolute quantification in proteomics using artificial QCAT proteins
      of concatenated signature peptides.
AB  - Absolute quantification in proteomics usually involves simultaneous determination
      of representative proteolytic peptides and stable isotope-labeled analogs. The
      principal limitation to widespread implementation of this approach is the
      availability of standard signature peptides in accurately known amounts. We
      report the successful design and construction of an artificial gene encoding a
      concatenation of tryptic peptides (QCAT protein) from several chick (Gallus
      gallus) skeletal muscle proteins and features for quantification and
      purification.

PMID- 16094384
TI  - Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and
      tandem mass spectrometry.
AB  - We present a robust and general method for the identification and relative
      quantification of phosphorylation sites in complex protein mixtures. It is based
      on a new chemical derivatization strategy using a dendrimer as a soluble polymer
      support and tandem mass spectrometry (MS/MS). In a single step, phosphorylated
      peptides are covalently conjugated to a dendrimer in a reaction catalyzed by
      carbodiimide and imidazole. Modified phosphopeptides are released from the
      dendrimer via acid hydrolysis and analyzed by MS/MS. When coupled with an initial
      antiphosphotyrosine protein immunoprecipitation step and stable-isotope labeling,
      in a single experiment, we identified all known tyrosine phosphorylation sites
      within the immunoreceptor tyrosine-based activation motifs (ITAM) of the T-cell
      receptor (TCR) CD3 chains, and previously unknown phosphorylation sites on total
      97 tyrosine phosphoproteins and their interacting partners in human T cells. The
      dynamic changes in phosphorylation were quantified in these proteins.

PMID- 16094385
TI  - A microfluidic culture platform for CNS axonal injury, regeneration and
      transport.
AB  - Investigation of axonal biology in the central nervous system (CNS) is hindered
      by a lack of an appropriate in vitro method to probe axons independently from
      cell bodies. Here we describe a microfluidic culture platform that polarizes the
      growth of CNS axons into a fluidically isolated environment without the use of
      targeting neurotrophins. In addition to its compatibility with live cell imaging,
      the platform can be used to (i) isolate CNS axons without somata or dendrites,
      facilitating biochemical analyses of pure axonal fractions and (ii) localize
      physical and chemical treatments to axons or somata. We report the first evidence
      that presynaptic (Syp) but not postsynaptic (Camk2a) mRNA is localized to
      developing rat cortical and hippocampal axons. The platform also serves as a
      straightforward, reproducible method to model CNS axonal injury and regeneration.
      The results presented here demonstrate several experimental paradigms using the
      microfluidic platform, which can greatly facilitate future studies in axonal
      biology.

PMID- 16094386
TI  - Real-time imaging of ligand-induced IKK activation in intact cells and in living
      mice.
AB  - The transcription factor NF-kappaB is a key regulator of cellular activation,
      proliferation and apoptosis. Defects in the NF-kappaB pathway contribute to a
      broad array of malignant, neurodegenerative and chronic inflammatory diseases.
      IKK-dependent IkappaB alpha degradation by the 26S proteasome is a critical NF
      kappaB regulatory control point, which is emerging as an important target for
      drug development. To directly monitor regulation of IKK activation in intact
      organisms, we engineered an IkappaB alpha-firefly luciferase (IkappaB alpha-FLuc)
      fusion reporter. In cultured cells and living animals, the reporter provided a
      continuous, noninvasive readout of the kinetics of ligand-induced IKK activation
      and the pharmacodynamics of selective inhibitors of both IKK and the 26S
      proteasome. This IkappaB alpha-FLuc reporter now permits continuous readout of
      IKK activation in vivo, facilitates development and validation of target-specific
      therapeutics, and complements conventional NF-kappaB transcriptional reporters
      for more complete temporal and regional investigations of the NF-kappaB signaling
      pathway in health and disease.

PMID- 16094389
TI  - Effect of volume guarantee combined with assist/control vs synchronized
      intermittent mandatory ventilation.
AB  - OBJECTIVE: To compare the effect of combining assist/control with volume
      guarantee (AC+VG) vs synchronized intermittent mandatory ventilation with VG
      (SIMV+VG) on tidal volume (V(T)), peak inspiratory pressure (PIP), mean airway
      pressure (MAP), respiratory rate, heart rate, oxygen saturation (SpO(2)), and
      minute volume (MV) in preterm infants. STUDY DESIGN: A total of 12 infants were
      randomized to receive AC+VG, followed by SIMV+VG, or the opposite sequence for
      four alternating 2-hour periods. RESULTS: Airway pressure of machine breaths was
      higher during SIMV. MV and V(Te) were similar, but more variable during
      synchronized intermittent mandatory ventilation. The V(Te) of unsupported breaths
      during SIMV was lower than machine breaths of SIMV and AC. There was more
      tachycardia and tachypnea with a lower and more variable SpO(2) during SIMV.
      CONCLUSIONS: SIMV+VG is associated with higher work of breathing indicated by
      tachycardia, tachypnea and lower SpO(2) compared to AC+VG. VG appears to be more
      effective when combined with AC than with SIMV.

PMID- 16094390
TI  - Discovery of the ubiquitin proteasome system and its involvement in apoptosis.

PMID- 16094391
TI  - Early work on the ubiquitin proteasome system, an interview with Avram Hershko.
      Interview by CDD.

PMID- 16094392
TI  - Early work on the ubiquitin proteasome system, an interview with Irwin Rose.
      Interview by CDD.

PMID- 16094393
TI  - Early work on the ubiquitin proteasome system, an interview with Aaron
      Ciechanover. Interview by CDD.

PMID- 16094394
TI  - Intracellular protein degradation: from a vague idea thru the lysosome and the
      ubiquitin-proteasome system and onto human diseases and drug targeting.
AB  - Between the 1950s and 1980s, scientists were focusing mostly on how the genetic
      code is transcribed to RNA and translated to proteins, but how proteins are
      degraded has remained a neglected research area. With the discovery of the
      lysosome by Christian de Duve, it was assumed that cellular proteins are degraded
      within this organelle. Yet, several independent lines of experimental evidence
      strongly suggested that intracellular proteolysis is largely nonlysosomal, but
      the mechanisms involved remained obscure. The discovery of the ubiquitin
      proteasome system resolved the enigma. We now recognize that degradation of
      intracellular proteins is involved in regulation of a broad array of cellular
      processes, such as cell cycle and division, regulation of transcription factors,
      and assurance of the cellular quality control. Not surprisingly, aberrations in
      the system have been implicated in the pathogenesis of human disease, such as
      malignancies and neurodegenerative disorders, which led subsequently to an
      increasing effort to develop mechanism-based drugs.

PMID- 16094395
TI  - The ubiquitin system for protein degradation and some of its roles in the control
      of the cell division cycle.
AB  - Owing to the intensive research activity on protein synthesis, little attention
      was paid in the 1950s and 1960s to protein degradation. However, work by my group
      and others between 1970 and 1990 led to the identification of the ubiquitin
      dependent degradation system. We found that this system contains three types of
      enzymes: E1 ubiquitin--activating enzyme, E2 ubiquitin--carrier enzyme and E3
      ubiquitin--protein ligase. The sequential action of these enzymes leads to
      conjugation of ubiquitin to proteins and then in most cases to their degradation.
      This review briefly tells the story of how this pathway was discovered describing
      the main findings that during the years allowed us to draw the complex picture we
      have now.

PMID- 16094396
TI  - Ubiquitin at Fox Chase.
AB  - My interest in protein breakdown as a research problem began in 1955. In 1963,
      when we relocated from Yale to the Institute for Cancer Research of Fox Chase,
      Philadelphia, nothing new was being reported. Here, I review how we get the
      ubiquitin proteasome system all together.

PMID- 16094397
TI  - Nitrosative and oxidative stress links dysfunctional ubiquitination to
      Parkinson's disease.

PMID- 16094398
TI  - IAPs--the ubiquitin connection.

PMID- 16094399
TI  - Ubiquitylation in apoptosis: DIAP1's (N-)en(d)igma.

PMID- 16094400
TI  - Proteases, proteasomes and apoptosis: breaking Ub is hard to do.

PMID- 16094401
TI  - Caspase inactivation of the proteasome.

PMID- 16094402
TI  - Serine proteases and calpains fulfill important supporting roles in the apoptotic
      tragedy of the cellular opera.

PMID- 16094403
TI  - Constitutive proteasome-mediated turnover of Bfl-1/A1 and its processing in
      response to TNF receptor activation in FL5.12 pro-B cells convert it into a
      prodeath factor.
AB  - Bfl-1/A1 is generally recognized as a Bcl-2-related inhibitor of apoptosis. We
      show that Bfl-1 undergoes constitutive ubiquitin/proteasome-mediated turnover.
      Moreover, while Bfl-1 suppresses apoptosis induced by staurosporine or cytokine
      withdrawal, it is proapoptotic in response to tumor necrosis factor (TNF)
      receptor activation in FL5.12 pro-B cells. Its anti- versus proapoptotic effect
      is regulated by two proteolytic events: (1) its constitutive proteasome-mediated
      turnover and (2) its TNF/cycloheximide (CHX)-induced cleavage by mu-calpain, or a
      calpain-like activity, coincident with acquisition of a proapoptotic phenotype.
      In vitro studies suggest that calpain-mediated cleavage of Bfl-1 occurs between
      its Bcl-2 homology (BH)4 and BH3 domains. This would be consistent with the
      generation of a proapoptotic Bax-like BH1-3 molecule. Overall, our studies
      uncovered two new regulatory mechanisms that play a decisive role in determining
      Bfl-1's prosurvival versus prodeath activities. These findings might provide
      important clues to counteract chemoresistance in tumor cells that highly express
      Bfl-1.

PMID- 16094404
TI  - Caspase activation and apoptosis in response to proteasome inhibitors.
AB  - Several studies have indicated that proteasome inhibitors (PIs) are promising
      anticancer agents. We have discovered that PIs have the unique ability to
      activate effector caspases through a mitochondrial Bcl-2 inhibitable but caspase
      9 independent pathway. Stabilization of released Smac induced by blockade of the
      proteasome could explain the apoptosome-independent cell death induced by PIs. In
      fact, Smac/DIABLO critically supports this PIs-dependent caspase activation. By
      using a new assay, we confirm that at a single cell level both Smac and PIs can
      activate caspases in the absence of the apoptosome. Moreover, we have observed
      two PIs-induced kinetics of caspase activation, with caspase-9 being still
      required for the rapid caspase activation in response to mitochondrial
      depolarization, but dispensable for the slow DEVDase activation. In summary, our
      data indicate that PIs can activate downstream caspases at least in part through
      Smac/DIABLO stabilization.

PMID- 16094406
TI  - Targeting the renin-angiotensin-aldosterone system in atrial fibrillation: from
      pathophysiology to clinical trials.

PMID- 16094407
TI  - Fibromuscular dysplasia: catheter, cut or laissez faire? That remains the
      question.

PMID- 16094408
TI  - Leptin is favourably associated with vascular function in obese Caucasians, but
      not in obese Africans.
AB  - The comparison of the associations between chronically elevated leptin levels and
      cardiovascular function in obese Africans and Caucasians has not yet been
      determined. Therefore, the aim of this study was to compare leptin's associations
      with cardiovascular function in obese African and obese Caucasian women to
      determine whether leptin's associations differ between these two groups. This
      study consisted of two case-case control studies. The first study included a
      sample of 102 apparently healthy African women and the second, 115 apparently
      healthy Caucasian women. All lean and obese subjects were selected from each
      study. The Finometer apparatus was used to obtain a more elaborate cardiovascular
      profile. Serum leptin levels, insulin levels and the lipid profile were
      determined. Stroke volume (SV) and cardiac output (CO) were significantly (P< or
      =0.01) elevated in both obese African and Caucasian groups compared to their lean
      controls. Total peripheral resistance (TPR) was significantly decreased and
      arterial compliance (C(W)) significantly increased in both obese African and
      Caucasian groups. In the obese Caucasian group, diastolic blood pressure (DBP)
      was significantly (P< or =0.01) lower, SV and C(W) significantly higher (P< or
      =0.01) and TPR significantly lower compared to the age, body mass index (BMI),
      and leptin-matched obese African group. After adjusting for age and BMI, leptin
      correlated negatively with DBP (P< or =0.05; r=-0.33) and TPR (P< or =0.05; r=
      0.36) in the obese Caucasian group, but not in the obese African group. Even
      though leptin levels were similar in obese African and Caucasian women, leptin is
      favourably associated with vascular function in obese Caucasians, but not in
      obese Africans.

PMID- 16094409
TI  - Maternal age in pregnancy and offspring blood pressure in childhood in the Avon
      Longitudinal Study of Parents and Children (ALSPAC).
AB  - Associations between maternal age in pregnancy and offspring blood pressure (BP)
      at age 7(1/2) were investigated in 7623 singletons from the Avon Longitudinal
      Study of Parents and Children (ALSPAC). In models adjusted for age and sex there
      was an inverse relationship between maternal age and BP in children: beta = -0.06
      mmHg per year of maternal age (95% CI -0.10 to -0.01, P = 0.02) for systolic BP
      and beta = -0.04 (95% CI -0.07 to -0.01, P = 0.02) for diastolic BP. However,
      this association disappeared after adjustment for confounding factors: beta = 
      0.02 mmHg per year of maternal age (95% CI -0.07 to 0.04, P = 0.5) for systolic
      BP and beta = -0.03 (95% CI -0.07 to 0.01, P = 0.2) for diastolic BP. We conclude
      that there is no evidence of a relationship between maternal age in pregnancy and
      childhood BP in this contemporary birth cohort.

PMID- 16094410
TI  - Gene transfer into human hematopoietic progenitor cells with an episomal vector
      carrying an S/MAR element.
AB  - Episomally maintained self-replicating systems present attractive alternative
      vehicles for gene therapy applications. Recent insights into the ability of
      chromosomal scaffold/matrix attachment regions (S/MARs) to mediate episomal
      maintenance of genetic elements allowed the development of a small circular
      episomal vector that functions independently of virally encoded proteins. In this
      study, we investigated the potential of this vector, pEPI-eGFP, to mediate gene
      transfer in hematopoietic progenitor cell lines and primary human cells. pEPI
      eGFP was episomally maintained and conferred sustained eGFP expression even in
      nonselective conditions in the human cell line, K562, as well as in primary human
      fibroblast-like cells. In contrast, in the murine erythroleukemia cell line, MEL,
      transgene expression was silenced through histone deacetylation, despite the
      vector's episomal persistence. Hematopoietic semisolid cell colonies derived from
      transfected human cord blood CD34(+) cells expressed eGFP, albeit at low levels.
      After 4 weeks, the vector is retained in approximately 1% of progeny cells. Our
      results provide the first evidence that S/MAR-based plasmids can function as
      stable episomes in primary human cells, supporting long-term transgene
      expression. However, they do not display universal behavior in all cell types.

PMID- 16094411
TI  - Adenoviral gene transfer of Akt enhances myocardial contractility and
      intracellular calcium handling.
AB  - The serine-threonine kinase Akt/PKB mediates stimuli from different classes of
      cardiomyocyte receptors, including the growth hormone/insulin like growth factor
      and the beta-adrenergic receptors. Whereas the growth-promoting and antiapoptotic
      properties of Akt activation are well established, little is known about the
      effects of Akt on myocardial contractility, intracellular calcium (Ca(2+))
      handling, oxygen consumption, and beta-adrenergic pathway. To this aim, Sprague
      Dawley rats were subjected to a wild-type Akt in vivo adenoviral gene transfer
      using a catheter-based technique combined with aortopulmonary crossclamping. Left
      ventricular (LV) contractility and intracellular Ca(2+) handling were evaluated
      in an isolated isovolumic buffer-perfused, aequorin-loaded whole heart
      preparations 10 days after the surgery. The Ca(2+)-force relationship was
      obtained under steady-state conditions in tetanized muscles. No significant
      hypertrophy was detected in adenovirus with wild-type Akt (Ad.Akt) versus
      controls rats (LV-to-body weight ratio 2.6+/-0.2 versus 2.7+/-0.1 mg/g, controls
      versus Ad.Akt, P, NS). LV contractility, measured as developed pressure,
      increased by 41% in Ad.Akt. This was accounted for by both more systolic Ca(2+)
      available to the contractile machinery (+19% versus controls) and by enhanced
      myofilament Ca(2+) responsiveness, documented by an increased maximal Ca(2+)
      activated pressure (+19% versus controls) and a shift to the left of the Ca(2+)
      force relationship. Such increased contractility was paralleled by a slight
      increase of myocardial oxygen consumption (14%), while titrated dose of
      dobutamine providing similar inotropic effect augmented oxygen consumption by 39%
      (P<0.01). Phospholamban, calsequestrin, and ryanodine receptor LV mRNA and
      protein content were not different among the study groups, while sarcoplasmic
      reticulum Ca(2+) ATPase protein levels were significantly increased in Ad.Akt
      rats. beta-Adrenergic receptor density, affinity, kinase-1 levels, and adenylyl
      cyclase activity were similar in the three animal groups. In conclusion, our
      results support an important role for Akt/PKB in the regulation of myocardial
      contractility and mechanoenergetics.

PMID- 16094412
TI  - Compliance of sildenafil treatment for erectile dysfunction and factors affecting
      it.
AB  - To assess the compliance of treatment, its affecting factors, and reasons for
      dropout, a questionnaire was mailed to a cohort of 2139 subjects who received
      sildenafil prescriptions for erectile dysfunction (ED) at our institution from
      1999 to 2002. A total of 726 subjects (34%) with a mean age of 67 years answered
      the questionnaires. The response rate for sildenafil treatment was 67%. Of these
      sildenafil responders, 43% reported that they continued using sildenafil while
      57% did not, in a mean follow-up of 3 years. Common reasons for discontinuation
      were effect below expectations, high cost, loss of interest in sex, and
      inconvenience in obtaining sildenafil. The continuers showed a higher rate than
      the discontinuers (P < 0.05) of having tried other treatments, dose titration,
      and a dose higher than 50 mg. The discontinuers reported having a lower mean
      responding dose and improvement score post sildenafil treatment than the
      continuers. In conclusion, effect below expectations was the leading reason for
      discontinuation of sildenafil treatment. How ED subjects tried the medication and
      the adequacy of education in the initial treatment period may impact the
      compliance of sildenafil treatment.

PMID- 16094413
TI  - Use of a validated quality of life questionnaire to assess sexual function
      following laparoscopic radical prostatectomy.
AB  - Wide variations exist in the methods for evaluating potency following radical
      prostatectomy. We describe our technique of laparoscopic radical prostatectomy
      (LRP), present our methods for assessing the return of potency following LRP, and
      discuss the relevant literature. Sexual function was assessed pre- and
      postoperatively using the Expanded Prostate Cancer Index Composite questionnaire
      (EPIC). Sexual function subscale scores (SFSS) were reported as a percentage of
      preoperative baseline sexual function. The EPIC was also used for single-question
      assessment of successful intercourse. We also reviewed the literature on
      prospective health-related quality of life results following LRP and open radical
      retropubic prostatectomy. Only patients reporting preoperative intercourse were
      analyzed. Of these, 72 and 35% undergoing bilateral and unilateral nerve sparing
      (NS) reported postoperative intercourse at 12 months (P=0.01). Mean SFSS at 12
      months was 61 and 57% of baseline after bilateral and unilateral NS, respectively
      (P=0.71). Following NS procedures, 74% of patients < or =58 years of age and 41%
      of patients >58 years of age reported successful intercourse at 12 months
      (P=0.015). Mean SFSS was 64 and 52% of baseline function (P=0.249) at 12 months
      for patients < or =58 and >58 years of age, respectively. In patients <58 years
      of age who underwent bilateral NS surgery, 82% reported intercourse at 12 months.
      In conclusion, return of sexual function following NS LRP in our experience is
      comparable to reports from centers of excellence in open prostatectomy.
      Standardizing data collection using validated quality of life instruments can
      provide both surgeon and patient with a realistic forecast of relative return to
      normal sexual function following prostatectomy.

PMID- 16094414
TI  - Male hypogonadism. Part II: etiology, pathophysiology, and diagnosis.
AB  - Male hypogonadism has a multifactorial etiology that includes genetic conditions,
      anatomic abnormalities, infection, tumor, and injury. Defects in the hypothalamic
      pituitary-gonadal axis may also result from type II diabetes mellitus and
      treatment with a range of medications. Circulating testosterone levels have been
      associated with sexual function, cognitive function, and body composition. Apart
      from reduced levels of testosterone, clinical hallmarks of hypogonadism include
      absence or regression of secondary sex characteristics, reduced fertility
      (oligospermia, azoospermia), anemia, muscle wasting, reduced bone mass (and bone
      mineral density), and/or abdominal adiposity. Some patients, particularly those
      with partial androgen deficiency of the aging male, also experience sexual
      dysfunction, reduced sense of vitality, depressed mood, increased irritability,
      difficulty concentrating, and/or hot flushes in certain cases of acute onset. As
      many patients with male hypogonadism-like patients with erectile dysfunction-do
      not seek medical attention, it is important for clinicians to be acquainted with
      the signs and symptoms of hypogonadism, and to conduct appropriate laboratory
      testing and other assessments to determine the causes and inform the treatment of
      this condition.

PMID- 16094415
TI  - Direct evidence for cooperating genetic events in the leukemic transformation of
      normal human hematopoietic cells.
AB  - Although genetic abnormalities associated with hematological malignancies are
      readily identified, the natural history of human leukemia cannot be observed
      because initiating and subsequent transforming events occur before clinical
      presentation. Furthermore, it has not been possible to study leukemogenesis in
      vitro as normal human cells do not spontaneously transform. Thus, the nature and
      sequence of genetic changes required to convert human hematopoietic cells into
      leukemia cells have never been directly examined. We have developed a system
      where the first step in the leukemogenic process is an engineered disruption of
      differentiation and self-renewal due to expression of the TLS-ERG oncogene,
      followed in some cases by overexpression of hTERT. In two of 13 experiments,
      transduced cells underwent step-wise transformation and immortalization through
      spontaneous acquisition of additional changes. The acquired karyotypic
      abnormalities and alterations including upregulation of Bmi-1 and telomerase all
      occur in acute myeloid leukemia (AML), establishing the relevance of this system.
      One resultant cell line studied in depth exhibits cellular properties
      characteristic of AML, notably a hierarchical organization initiated by leukemic
      stem cells that differentiate abnormally. These findings provide direct evidence
      for multiple cooperating events in human leukemogenesis, and provide a foundation
      for studying the genetic changes that occur during leukemic initiation and
      progression.

PMID- 16094416
TI  - Clinical and biological relevance of single-nucleotide polymorphisms and acquired
      somatic mutations of the BCL6 first intron in follicular lymphoma.
AB  - Genetic modifications of the BCL6 gene in lymphoma include translocations,
      deletions, and somatic mutations (SM) of the 5' noncoding region. Three single
      nucleotide polymorphisms (SNPs) of the major mutation cluster region (MMC) have
      been reported, including two substitutions (397G/C, 502G/A) and one deletion
      (520DeltaT). Clinical and biological relevance of these SNPs are unknown. Based
      on a case-control study, BCL6 SNPs frequencies were assessed in 97 t(14;18)
      follicular lymphomas (FL) and in 54 lymphomas with 3q27 rearrangement. Allele
      frequencies were similar in the FL and controls groups. The 397 G/C genotype was
      correlated to a higher-grade transformation risk (P=0.02). SM were observed in
      39.1% of FL and were characterized by a clustering distribution (hot spots
      spanning position 420-435, 106-127, and 590-600). No correlation between
      genotypes or acquired mutational status and BCL6 expression was demonstrated.
      However, gel mobility-shift assays, using SNPs containing probes show results
      representative for protein/DNA complexes. This study demonstrates that the first
      BCL6 intron is a highly variable region as a consequence of both SNP and SM,
      which may contribute to biology and outcome of FL.

PMID- 16094417
TI  - Fulminant B hepatitis in a surface antigen-negative patient with B-cell chronic
      lymphocytic leukaemia after rituximab therapy.

PMID- 16094418
TI  - Cytogenetic analysis delineates a spectrum of chromosomal changes that can
      distinguish non-MALT marginal zone B-cell lymphomas among mature B-cell entities:
      a description of 103 cases.
AB  - The purpose of this study was to document the frequency and distribution of
      karyotypic changes present at diagnosis in 103 non-MALT marginal zone cell
      lymphoma (MZL) patients. This cytogenetic analysis of a large cohort extends
      previous observations and allows the identification of new cytogenetic features.
      Abnormalities identified in more than 15% of patients included +3/+3q (37%), 7q
      deletions (31%), +18/+18q (28%), 6q deletions (19%), +12/+12q (15%) and 8p
      deletions (15%). Trisomy 3/3q, 7q deletions, +18 and +12 were seen in different
      combinations in more than 30% of patients in comparison to 2% in lymphocytic
      lymphomas/chronic lymphocytic leukemias, 1% in mantle cell lymphomas and 7% in
      follicular lymphomas. The marked propensity of these abnormalities to be
      recurrently associated with the same tumoral clone of individual karyotypes
      allowed the delineation of a cytogenetic profile that may help to distinguish non
      MALT MZL among other mature B-cell neoplasms. If +3/3q, +12/+12q, and 6q, 7q and
      8p deletions were significantly associated with clinical prognostic factors
      previously reported to influence survival and time to progression, patients
      displaying these abnormalities did not experience a significantly shorter time to
      progression.

PMID- 16094420
TI  - Increased expression of CD152 (CTLA-4) by normal T lymphocytes in untreated
      patients with B-cell chronic lymphocytic leukemia.
AB  - Patients with chronic lymphocytic leukemia (CLL) have defects in both cellular
      and humoral immunity. Since CD152 (CTLA-4) plays a critical role in
      downregulating T-cell responses, we studied the expression of surface and
      cytoplasmic CD152 (sCD152 and cCD152, respectively) in freshly isolated T cells
      from treatment-naive patients with CLL. CD4+ and CD8+ T cells from these patients
      demonstrated significantly increased sCD152 and cCD152 compared to normal donors.
      Furthermore, these patients had an increased proportion of the regulatory
      CD4(+)/CD25(+)/CD152+ subset that correlated with advanced Rai stage, unfavorable
      cytogenetics and low serum IgG and IgA levels. The expression of sCD152 by T
      cells also correlated with ZAP-70 expression by CLL B cells. The proportion of
      CD4(+)/CD25+ cells was also correlated with unmutated immunoglobulin heavy chain
      variable gene status. Blockade of CD152 with monoclonal antibody (mAb) in
      proliferation assays was associated with potent T-cell proliferation in response
      to autologous and allogeneic CD40-activated CLL B cells. In summary, T cells from
      patients with CLL may be primed for anergy by expressing increased amounts of
      CD152; anti-CD152 mAb may represent a therapeutic opportunity to enhance an
      immune response against autologous leukemia cells.

PMID- 16094421
TI  - Novel targeted drugs for the treatment of multiple myeloma: from bench to
      bedside.
AB  - Multiple myeloma remains an incurable plasma cell neoplasm. New insights into its
      pathogenesis have identified signaling pathways that have become potential
      therapeutic targets. It has clearly been established that intracellular
      regulatory proteins and interactions between malignant plasma cells and the bone
      marrow microenvironment play an important role in their survival and drug
      resistance. Several new agents associated with molecular targets are currently
      being investigated to design new treatment strategies aimed at prolonging
      survival and improving quality of life. This review illustrates their mechanisms
      of action and the possible future clinical applications.

PMID- 16094422
TI  - Oncogenic potential of the transcription factor LYL1 in acute myeloblastic
      leukemia.
AB  - The LYL1 gene encodes a basic helix-loop-helix transcription factor involved in T
      cell acute lymphoblastic leukemia. Using real-time quantitative RT-PCR assay, we
      found that the expression of LYL1 was at higher levels in the majority cases of
      acute myeloblastic leukemia (AML) or myelodysplastic syndrome when compared to
      normal bone marrow. Our study also showed that LYL1 was highly expressed in most
      AML cell lines and in CD34+ AML cells. To determine whether LYL1 had an affect on
      the phenotype and behavior of myeloid cells, we introduced full-length LYL1 cDNA
      into K562 cells using electroporation and U937 cells with retroviral infection.
      Both of the derivative cell lines with overexpression of LYL1 had an increased
      growth rate and clonogenecity. Forced expression of LYL1 in K562 cells enhanced
      spontaneous and hemin-induced erythroid differentiation but blocked spontaneous
      as well as PMA-induced megakaryocytic differentiation. Overexpression of LYL1 in
      U937 cells blocked all-trans retinoic acid-induced monocytic differentiation. The
      LYL1-transfected U937 cells were also more resistant to the cytotoxic drug
      cytarabine. These results demonstrate that LYL1 may play a role in early
      hematopoiesis and may be a potential oncogenic factor in AML.

PMID- 16094423
TI  - A genetic and molecular profile of third chromosome centric heterochromatin in
      Drosophila melanogaster.
AB  - In this review, we combine the results of our published and unpublished work with
      the published results of other laboratories to provide an updated map of the
      centromeric heterochromatin of chromosome 3 in Drosophila melanogaster. To date,
      we can identify more than 20 genes (defined DNA sequences with well-characterized
      functions and (or) defined genetic complementation groups), including at least 16
      essential loci. With the ongoing emergence of data from genetic, cytological, and
      genome sequencing studies, we anticipate continued, substantial progress towards
      understanding the function, structure, and evolution of centric heterochromatin.

PMID- 16094424
TI  - Microsatellite markers linked to 2 powdery mildew resistance genes introgressed
      from Triticum carthlicum accession PS5 into common wheat.
AB  - Two dominant powdery mildew resistance genes introduced from Triticum carthlicum
      accession PS5 to common wheat were identified and tagged using microsatellite
      markers. The gene designated PmPS5A was placed on wheat chromosome 2AL and linked
      to the microsatellite marker Xgwm356 at a genetic distance of 10.2 cM. Based on
      the information of its origin, chromosome location, and reactions to 5 powdery
      mildew isolates, this gene could be a member of the complex Pm4 locus. The 2nd
      gene designated PmPS5B was located on wheat chromosome 2BL with 3 microsatellite
      markers mapping proximally to the gene: Xwmc317 at 1.1 cM; Xgwm111 at 2.2 cM; and
      Xgwm382 at 4.0 cM; and 1 marker, Xgwm526, mapping distally to the gene at a
      distance of 18.1 cM. Since this gene showed no linkage to the other 2 known
      powdery mildew resistance genes on wheat chromosome 2B, Pm6 and Pm26, we believe
      it is a novel powdery mildew resistance gene and propose to designate this gene
      as Pm33.

PMID- 16094425
TI  - Origin, structure, and behavior of a highly rearranged deletion chromosome 1BS-4
      in wheat.
AB  - Wheat (Triticum aestivum L.) deletion (del) stocks are valuable tools for the
      physical mapping of molecular markers and genes to chromosome bins delineated by
      2 adjacent deletion breakpoints. The wheat deletion stocks were produced by using
      gametocidal genes derived from related Aegilops species. Here, we report on the
      origin, structure, and behavior of a highly rearranged chromosome 1BS-4. The
      cytogenetic and molecular marker analyses suggest that 1BS-4 resulted from 2
      breakpoints in the 1BS arm and 1 breakpoint in the 1BL arm. The distal segment
      from 1BS, except for a small deleted part, is translocated to the long arm.
      Cytologically, chromosome 1BS-4 is highly stable, but shows a unique meiotic
      pairing behavior. The short arm of 1BS-4 fails to pair with a normal 1BS arm
      because of lack of homology at the distal ends. The long arm of 1BS-4 only pairs
      with a normal 1BS arm within the distal region translocated from 1BS. Therefore,
      using the 1BS-4 deletion stock for physical mapping will result in the false
      allocation of molecular markers and genes proximal to the breakpoint of 1BS-4.

PMID- 16094427
TI  - Analysis of expressed sequence tags of the water flea Daphnia magna.
AB  - To study gene expression in the water flea Daphnia magna we constructed a cDNA
      library and characterized the expressed sequence tags (ESTs) of 7210 clones. The
      EST sequences clustered into 2958 nonredundant groups. BLAST analyses of both
      protein and DNA databases showed that 1218 (41%) of the unique sequences shared
      significant similarities to known nucleotide or amino acid sequences, whereas the
      remaining 1740 (59%) showed no significant similarities to other genes.
      Clustering analysis revealed particularly high expression of genes related to ATP
      synthesis, structural proteins, and proteases. The cDNA clones and EST sequence
      information should be useful for future functional analysis of daphnid biology
      and investigation of the links between ecology and genomics.

PMID- 16094428
TI  - Ancient differentiation of the H and I haplomes in diploid Hordeum species based
      on 5S rDNA.
AB  - 5S rDNA clones from 12 South American diploid Hordeum species containing the HH
      genome and 3 Eurasian diploid Hordeum species containing the II genome, including
      the cultivated barley Hordeum vulgare, were sequenced and their sequence
      diversity was analyzed. The 374 sequenced clones were assigned to "unit classes",
      which were further assigned to haplomes. Each haplome contained 2 unit classes.
      The naming of the unit classes reflected the haplomes, viz. both the long H1 and
      short I1 unit classes were identified with II genome diploids, and both the long
      H2 and long Y2 unit classes were recognized in South American HH genome diploids.
      Based upon an alignment of all sequences or alignments of representative
      sequences, we tested several evolutionary models, and then subjected the
      parameters of the models to a series of maximum likelihood (ML) analyses and
      various tests, including the molecular clock, and to a Bayesian evolutionary
      inference analysis using Markov chain Monte Carlo (MCMC). The best fitting model
      of nucleotide substitution was the HKY+G (Hasegawa, Kishino, Yano 1985 model with
      the Gamma distribution rates of nucleotide substitutions). Results from both ML
      and MCMC imply that the long H1 and short I unit classes found in the II genome
      diploids diverged from each other at the same rate as the long H2 and long Y2
      unit classes found in the HH genome diploids. The divergence among the unit
      classes, estimated to be circa 7 million years, suggests that the genus Hordeum
      may be a paleopolyploid.

PMID- 16094429
TI  - Linkage map of birch, Betula pendula Roth, based on microsatellites and amplified
      fragment length polymorphisms.
AB  - The first genetic linkage map for silver birch, Betula pendula Roth, was
      constructed by using a pseudo-testcross mapping strategy and integration of
      linkage data from 3 unrelated 2-generation pedigrees. The map is based on the
      genetic inheritance and segregation of 82 amplified fragment length
      polyhmorphisms and 19 microsatellite markers, and was constructed by
      simultaneously comparing the performance of CRI-MAP and OUTMAP packages. The
      analysis revealed 16 linkage groups, and the total map coverage is 1561 cM
      (Kosambi units). Average map distance between adjacent markers is 15.5 cM.
      Linkage groups range between 6 and 18 loci and from 81.2 to 326.5 cM; the
      remaining 9 linkage groups consist of 2 or 3 loci ranging from 6.3 to 42.4 cM.
      The uncertainty of the map is illustrated with sensitivity analysis. This initial
      map can serve as a basis for developing a more detailed genetic map.

PMID- 16094430
TI  - Integration of molecular and classical linkage groups of the silkworm, Bombyx
      mori (n = 28).
AB  - Previously published linkage groups (LGs) composed of molecular markers were
      assigned to classical LGs in the silkworm, Bombyx mori (n = 28). Four markers
      from the classical linkage map, og, w-1, Lp, and Pfl, were assigned to the
      molecular linkage maps using sequence tagged sites. In addition, linkage analysis
      was carried out using BF1 progeny between wild-type and mutant stocks carrying
      morphological phenotypic markers. As a result, the counterparts for 26 of 28
      molecular LGs were identified with their counterparts of the classical LGs. Two
      visible markers, Sel and Xan, representing different classical LGs, were found to
      be linked.

PMID- 16094431
TI  - Identification by genome scanning approach (GSA) of a microsatellite tightly
      associated with the apple scab resistance gene Vm.
AB  - For all known major apple scab resistance genes except Vr, molecular markers have
      been published. However, the precise position of some of these genes, in the
      apple genome, remains to be identified. Knowledge about the relative position of
      apple scab resistance genes is necessary to preliminarily evaluate the
      probability of success of their pyramidization. Pyramidization of different
      resistance genes into the same genotype is a reliable way to create cultivars
      with durable apple scab resistance. Applying the genome scanning approach (GSA),
      we identified the linkage group of the scab resistance gene Vm, derived from
      Malus micromalus, and we found a new molecular marker tightly associated with the
      gene. The simple sequence repeat Hi07h02, previously mapped on linkage group 17,
      cosegregates with the Vm gene (no recombinants in the 95 plants tested). The
      already published sequence-characterized amplified region Vm marker OPB12(687)
      was found to be linked at about 5 cM from the resistance gene and, therefore,
      this marker also maps on linkage group 17 of apple. This is the first report of
      the discovery of a major apple scab resistance gene on linkage group 17. The
      advantages of using GSA for the identification of molecular markers for
      qualitative traits are discussed.

PMID- 16094426
TI  - Analyzing the potato abiotic stress transcriptome using expressed sequence tags.
AB  - To further increase our understanding of responses in potato to abiotic stress
      and the potato transcriptome in general, we generated 20 756 expressed sequence
      tags (ESTs) from a cDNA library constructed by pooling mRNA from heat-, cold-,
      salt-, and drought-stressed potato leaves and roots. These ESTs were clustered
      and assembled into a collection of 5240 unique sequences with 3344 contigs and
      1896 singleton ESTs. Assignment of gene ontology terms (GOSlim/Plant) to the
      sequences revealed that 8101 assignments could be made with a total of 3863
      molecular function assignments. Alignment to a set of 78 825 ESTs from other
      potato cDNA libraries derived from root, leaf, stolon, tuber, germinating eye,
      and callus tissues revealed 1476 sequences unique to abiotic stressed potato leaf
      and root tissue. Sequences present within the 5240 sequence set had similarity to
      genes known to be involved in abiotic stress responses in other plant species
      such as transcription factors, stress response genes, and signal transduction
      processes. In addition, we identified a number of genes unique to the abiotic
      stress library with unknown function, providing new candidate genes for
      investigation of abiotic stress responses in potato.

PMID- 16094432
TI  - Use of tall fescue EST-SSR markers in phylogenetic analysis of cool-season forage
      grasses.
AB  - Microsatellites or simple sequence repeats (SSRs) are highly useful molecular
      markers for plant improvement. Expressed sequence tag (EST)-SSR markers have a
      higher rate of transferability across species than genomic SSR markers and are
      thus well suited for application in cross-species phylogenetic studies. Our
      objectives were to examine the amplification of tall fescue EST-SSR markers in 12
      grass species representing 8 genera of 4 tribes from 2 subfamilies of Poaceae and
      the applicability of these markers for phylogenetic analysis of grass species.
      About 43% of the 145 EST-SSR primer pairs produced PCR bands in all 12 grass
      species and had high levels of polymorphism in all forage grasses studied. Thus,
      these markers will be useful in a variety of forage grass species, including the
      ones tested in this study. SSR marker data were useful in grouping genotypes
      within each species. Lolium temulentum, a potential model species for cool-season
      forage grasses, showed a close relation with the major Festuca-Lolium species in
      the study. Tall wheat grass was found to be closely related to hexaploid wheat,
      thereby confirming the known taxonomic relations between these species. While
      clustering of closely related species was found, the effectiveness of such data
      in evaluating distantly related species needs further investigations. The
      phylogenetic trees based on DNA sequences of selected SSR bands were in agreement
      with the phylogenetic relations based on length polymorphism of SSRs markers.
      Tall fescue EST-SSR markers depicted phylogenetic relations among a wide range of
      cool-season forage grass species and thus are an important resource for
      researchers working with such grass species.

PMID- 16094433
TI  - Unusual compact rDNA gene arrangements within some members of the Ascomycota:
      evidence for molecular co-evolution between ITS1 and ITS2.
AB  - The internal transcribed spacers of the ribosomal DNA tandem repeat were examined
      in members of the ascomycetous genus Sphaeronaemella. Species of Sphaeronaemella
      and its mitotic counterpart Gabarnaudia, have a compact rDNA gene arrangement due
      to unusually short internal transcribed spacer (ITS) regions. Examination of
      these regions from phylogenetically related taxa, Cornuvesica, Gondwanamyces, and
      Ceratocystis, showed that their ITS1 and ITS2 regions could be folded into
      central hairpin-like structures with the size reduction in species of
      Sphaeronaemella being due to length reduction of the main-hairpin and the loss of
      smaller hairpin-like structures that emanate from the main hairpin. A databank
      compilation, combined with newly obtained sequences, provided an ITS data set
      that includes sequences of 600 species belonging to the Ascomycota. Correlation
      analysis revealed that the sizes of ITS1 and ITS2 show a strong positive
      correlation, suggesting that the 2 rDNA regions have co-evolved. This supports
      biochemical evidence indicating that the ITS1 and ITS2 segments interact to
      facilitate the maturation of the rRNA precursor.

PMID- 16094434
TI  - Evidence of diversity within the SnRK1b gene family of Hordeum species.
AB  - Adaptor-specific polymerase chain reaction (PCR) was used to amplify 3 different
      products, termed variant A, B, and C, from the seed-specific class (SnRK1b) of
      the sucrose nonfermenting-1-related protein kinase gene family (SnRK1) of
      different Hordeum species and cultivars of barley (Hordeum vulgare). Standard PCR
      or reverse transcription-PCR (RT-PCR) at a high temperature, using primers that
      differed by 1 or 2 nucleotides, was then used to amplify and clone 3 specific
      variants. One primer pair amplified a variant from I genome species suggesting
      that this could be a useful I-genome specific marker. The corresponding genes of
      the 3 variants (A, B, and C) were termed SnRK1b.1, 2, and 3, respectively.
      SnRK1b.1 and 2, showed 98% - 100% nucleotide sequence identity in the coding
      region, and 89% - 90% identity in the promoter region (up to 200 bp upstream of
      the translation start site, ATG). However, they differed in having insertions,
      deletions, and base pair changes at potentially important sites in the polymerase
      binding regions. SnRK1b.3 showed 90% nucleotide sequence identity with SnRK1b.1
      in the coding region and 86% in the promoter region. This gene predominates in H
      genome species within the genus Hordeum and could be a useful marker for this
      group.

PMID- 16094435
TI  - Use of cpSSRs for the characterisation of yam phylogeny in Benin.
AB  - The Dioscorea cayenensis - Dioscorea rotundata species complex is the most widely
      cultivated yam in West Africa. This species complex has been described as
      deriving from wild yams belonging to the Enanthiophyllum section through
      domestication by African farmers. To study patterns of yam evolution and to
      establish phylogenetic relationships existing between wild and cultivated species
      sampled in Benin, we investigated changes in chloroplast DNA simple sequence
      repeats (cpSSR) in 148 yam accessions selected to cover the wider possible
      genetic diversity existing in the country. Dioscorea cayenensis and D. rotundata
      share the same haplotype. The morphotype "abyssinica" appeared to be subdivided
      into 2 haplotypes. One of these haplotypes shares the same haplotype with the
      Dioscorea cayenensis - Dioscorea rotundata species complex and with morphotypes
      praehensilis, suggesting that they might belong to the same species.
      Relationships among sections Lasiophyton, Macrocapaea, Opsophyton, and
      Enanthiophyllum were clarified, and some taxonomic changes within the
      Enanthiophyllum section were suggested. Dioscorea minutiflora, D. smilacifolia,
      and D. burkilliana might be considered as 1 single genetic group, and they are
      suspected of belonging to the same species.

PMID- 16094436
TI  - A library of Solanum lycopersicoides introgression lines in cultivated tomato.
AB  - A set of introgression lines (ILs), containing individual chromosome segments
      from the wild nightshade Solanum lycopersicoides bred into the genetic background
      of cultivated tomato (Lycopersicon esculentum), has been developed. A primary
      group of 56 lines was selected for maximum representation of the S.
      lycopersicoides genome (approximately 96% of the total map units), homozygosity,
      and a minimum number of introgressed segments per line. A secondary set of 34
      lines provides increased map resolution in certain regions. Approximately 34% of
      the lines were sterile in the homozygous condition, but could be maintained by
      heterozygotes. To facilitate identification of segregating ILs, restriction
      fragment length polymorphism probes were converted to higher throughput cleaved
      amplified polymorphic sequence markers, which supplement allozyme and
      morphological loci. Strong segregation distortion was observed in F2 progeny of
      heterozygous ILs, with an excess of L. esculentum alleles in most regions. For
      introgressions on distal chromosome 1L, a preferential transmission of S.
      lycopersicoides alleles was observed in the male germ line. Homozygous ILs
      generally yielded less seed from self pollination than corresponding
      heterozygotes, indicating that sterility effects were recessive. This IL library
      provides a novel resource for genetic studies of traits found in S.
      lycopersicoides.

PMID- 16094437
TI  - Construction of 2 intraspecific linkage maps and identification of resistance
      QTLs for Phytophthora capsici root-rot and foliar-blight diseases of pepper
      (Capsicum annuum L.).
AB  - Two linkage maps of pepper were constructed and used to identify quantitative
      trait loci (QTLs) conferring resistance to Phytophthora capsici. Inoculations
      were done with 7 isolates: 3 from Taiwan, 3 from California, and 1 from New
      Mexico. The first map was constructed from a set of recombinant inbred lines
      (RILs) of the PSP-11 (susceptible) x PI201234 (resistant) cross; and the second
      map was from a set of F(2) lines of the Joe E. Parker' (susceptible) x 'Criollo
      de Morelos 334' (resistant) cross. The RIL map covered 1466.1 cM of the pepper
      genome, and it consisted of 144 markers -- 91 amplified fragment length
      polymorphisms (AFLPs), 34 random amplified polymorphic DNA (RAPDs), 15 simple
      sequence repeats (SSRs), 1 sequence characterized amplified region (SCAR), and 3
      morphological markers -- distributed over 17 linkage groups. The morphological
      markers mapped on this population were erect fruit habit (up), elongated fruit
      shape (fs(e)), and fasciculate fruit clusters (fa). The F(2) map consisted of 113
      markers (51 AFLPs, 45 RAPDs, 14 SSRs, and 3 SCARs) distributed in 16 linkage
      groups, covering a total of 1089.2 cM of the pepper genome. Resistance to both
      root rot and foliar blight were evaluated in the RIL population using the 3
      Taiwan isolates; the remaining isolates were used for the root-rot test only.
      Sixteen chromosomal regions of the RIL map contained single QTLs or clusters of
      resistance QTLs that had an effect on root rot and (or) foliar blight, revealing
      a complex set of genetics involved in resistance to P. capsici. Five QTLs were
      detected in the F(2) map that had an effect on resistance to root rot.

PMID- 16094438
TI  - Tarsus determination in Drosophila melanogaster.
AB  - Arista versus tarsus determination is well investigated in Drosophila, yet it
      remains unresolved whether Antennapedia (ANTP) cell autonomously or noncell
      autonomously determines tarsus identity and whether Sex combs reduced (SCR) is
      the HOX protein required for normal tarsus determination. Three observations rule
      out a cell autonomous role for ANTP in tarsus determination. (i) Clonal ectopic
      overexpression of ANTP did not repress the expression of the arista determining
      protein Homothorax (HTH) in early 3rd stadium antennal imaginal discs. (ii)
      Clonal ectopic expression of ANTP did not transform the arista to a tarsus. (iii)
      Ectopic overexpression of ANTP, Labial (LAB), Deformed (DFD), SCR, Ultrabithorax
      (UBX), Abdominal-A (ABD-A), or Abdominal-B (ABD-B), using the dppGAL4 driver,
      resulted in arista-to-tarsus transformations, and repressed HTH/Extradenticle
      (EXD) activity noncell autonomously in early 3rd stadium antennal imaginal discs.
      SCR may not be the HOX protein required for normal tarsus determination, because
      co-ectopic expression of Proboscipedia (PB) inhibited the arista-to-tarsus
      transformations induced by ectopic expression of DFD, SCR, ANTP, UBX, ABD-A, and
      ABD-B. The proposal that SCR is the HOX protein required for normal tarsus
      determination is dependent on SCR being the sole target of PB suppression, which
      is not the case. Therefore, the possibility exists that normal tarsus
      determination is HOX independent.

PMID- 16094439
TI  - In vivo performance of a dual genetic marker, manA-gfp, in transgenic bentgrass.
AB  - A dual-marker combination, manA-gfp, comprising 2 independent expression
      cassettes of genes encoding an Escherichia coli phosphomannose isomerase (PMI)
      and a synthetic green fluorescent protein (GFP), was incorporated into the binary
      vector pPZP201. Agrobacterium tumefaciens-mediated transfer was used to introduce
      the manA-gfp into the mature-seed derived calli of Agrostis stoloifera L.
      'Crenshaw'. The putative transgenic bentgrass calli were screened in Murashige
      and Skoog medium containing 15 g mannose/L, in conjunction with a visual
      examination of the GFP expression with a fluorescence stereomicroscope. Calli
      with GFP fluorescence grew well on the mannose selection media. A total of 24
      transgenic plants derived from a single piece of callus lobe were studied for the
      genomic integration, expression, and function of the transgene. Genomic
      integration of the dual markers manA and gfp was confirmed by Southern blotting
      analysis, and the expression of manA also was validated by using PMI-specific
      antiserum. The inheritance and expression of the dual marker, manA-gfp, was
      demonstrated in the T1 generation. This study on the environmentally friendly
      markers further documented the feasibility of using alternative selection methods
      without using herbicide- or antibiotic-resistance markers.

PMID- 16094440
TI  - Assessment of the genetic diversity and phylogenetic relationships of a temperate
      bamboo collection by using transferred EST-SSR markers.
AB  - Polymorphic expressed sequence tag - simple sequence repeat (EST-SSR) markers
      derived from major cereal crops were used to assess the genetic diversity of the
      USDA temperate bamboo collection consisting of 92 accessions classified in 11
      separate genera and 44 species. A total of 211 bands were detected with a mean
      number of alleles per locus of 8.440. Phylogenetic relationships were determined
      by calculating genetic distances between all pairwise combinations and assessing
      differences in character data. The resulting dendrograms (unweighted pair group
      method with arithmetic means (UPGMA) and parsimony) clustered the accessions into
      2 main clades, which corresponded to accessions characterized morphologically as
      either clumping (sympodial) or running (monopodial) bamboos. The majority of the
      accessions clustered according to their current taxonomic classification. These
      markers were also beneficial in identifying contaminated and (or) misidentified
      plots. Overall, these transferred markers were informative in differentiating the
      various bamboo accessions and determining the level of genetic variation within
      and among species and genera.

PMID- 16094441
TI  - Genetic analysis and high-resolution mapping of a premature senescence gene
      Pse(t) in rice (Oryza sativa L.).
AB  - A rice mutant, designated pse(t) (premature senescence, tentatively), was
      isolated from a T-DNA-inserted transgenic population. Senescence advanced more
      markedly in pse(t) than in wild-type ('Zhonghua 11', japonica) plants. Genetic
      analysis of pse(t) revealed that the premature senescence mutation was controlled
      by a single recessive nuclear gene, but that it was not induced by T-DNA
      insertion. In an effort to understand the genetic and molecular basis underlying
      premature senescence in rice, a map-based cloning strategy was used to localize
      Pse(t). High-resolution mapping of the Pse(t) locus was carried out using simple
      sequence repeat (SSR) and cleaved amplified polymorphic sequence (CAPS) markers.
      An F2 population, comprising 1691 pse(t) individuals derived from a cross of the
      pse(t) mutant with 'Longtepu' (indica), was constructed. Several new polymorphism
      markers were developed in this study. Genetic linkage analysis showed that the
      Pse(t) gene was located on the long arm of chromosome 7. It was found that the
      Pse(t) gene cosegregated with 3 markers and was flanked by markers SS22 and PP21.
      Thus, the Pse(t) gene is located within a genetic distance of 0.15 cM,
      corresponding to a physical distance of 220 kb. These findings provide the basic
      information that can be used for the final isolation of this gene in the rice
      premature-senescence pathway.

PMID- 16094442
TI  - Colour genes (R and Rc) for grain and coleoptile upregulate flavonoid
      biosynthesis genes in wheat.
AB  - Pigmentation of wheat grain and coleoptile is controlled by the R gene on
      chromosomes of the homoeologous group 3 and the Rc gene on chromosomes of the
      homoeologous group 7, respectively. Each of these genes is inherited
      monogenically. The pigment of grain has been suggested to be a derivative of
      catechin-tannin and that of coleoptile to be anthocyanin. These polyphenol
      compounds are known to be synthesized through the flavonoid biosynthesis pathway.
      We isolated 4 partial nucleotide sequences of the early flavonoid biosynthesis
      genes (CHS, CHI, F3H, and DFR) in wheat. The expression of these genes was
      examined in the developing grain of red-grained and white-grained wheat lines.
      CHS, CHI, F3H, and DFR were highly upregulated in the grain coat tissue of the
      red-grained lines, whereas there was no significant expression in the white
      grained lines. These results indicate that the R gene is involved in the
      activation of the early flavonoid biosynthesis genes. As for coleoptile
      pigmentation, all 4 genes were expressed in the red coleoptile; however, DFR was
      not activated in the white coleoptile. The Rc gene appears to be involved in DFR
      expression. The possibility that wheat R and Rc genes might be transcription
      factors is discussed.

PMID- 16094443
TI  - Molecular markers for seed colour in Brassica juncea.
AB  - A detailed RFLP map was used to map QTLs associated with seed colour in Brassica
      juncea using a doubled-haploid population derived from a cross between a
      black/brown-seeded cultivar and a yellow-seeded breeding line. Segregation
      analysis suggested that seed colour was under control of 2 unlinked loci with
      duplicate gene action. However, QTL analysis revealed 3 QTLs, SC-B4, SC-A10 and
      SC-A6, affecting seed colour. The QTLs were consistent across environments, and
      individually explained 43%, 31%, and 16%, respectively, and collectively 62% of
      the phenotypic variation in the population. Digenic interaction analysis showed
      that closest flanking locus of QTL SC-B4, wg7b6cNM, had strong epistasis with the
      locus wg5a1a, which is tightly linked to QTL SC-A6. The interaction of these 2
      loci explained 27% of the phenotypic variation in the population, while the whole
      model explained 84%. In a multiple regression model, the effects of QTL SC-A10,
      as well as its interaction with other loci, were non-significant, whereas the
      effects of loci wg7b6cNM and wg5a1a and their interaction were significant.
      Ninety-eight percent of the DH lines carried the expected alleles of loci
      wg7b6cNM and wg5a1a for seed colour, confirming that only these 2 loci were
      linked to seed colour in B. juncea. Four additional digenic interactions
      significantly affected seed colour, and all 5 digenic interactions were
      consistent across environments.

PMID- 16094444
TI  - Chromatin remodeling complexes: ATP-dependent machines in action.
AB  - Since the initial characterization of chromatin remodeling as an ATP-dependent
      process, many studies have given us insight into how nucleosome-remodeling
      complexes can affect various nuclear functions. However, the multistep DNA
      histone remodeling process has not been completely elucidated. Although new
      studies are published on a nearly weekly basis, the nature and roles of
      interactions of the individual SWI/SNF- and ISWI-based remodeling complexes and
      DNA, core histones, and other chromatin-associated proteins are not fully
      understood. In addition, the potential changes associated with ATP recruitment
      and its subsequent hydrolysis have not been fully characterized. This review
      explores possible mechanisms by which chromatin-remodeling complexes are
      recruited to specific loci, use ATP hydrolysis to achieve actual remodeling
      through disruption of DNA-histone interactions, and are released from their
      chromatin template. We propose possible roles for ATP hydrolysis in a chromatin
      release/target-scanning process that offer an alternative to or complement the
      often overlooked function of delivering the energy required for sliding or
      dislodging specific subsets of core histones.

PMID- 16094445
TI  - Nuclear receptor coactivators: the key to unlock chromatin.
AB  - The biological effects of hormones, ranging from organogenesis, metabolism, and
      proliferation, are transduced through nuclear receptors (NRs). Over the last
      decade, NRs have been used as a model to study transcriptional control. The
      conformation of activated NRs is favorable for the recruitment of coactivators,
      which promote transcriptional activation by directly communicating with
      chromatin. This review will focus on the function of different classes of
      coactivators and associated complexes, and on progress in our understanding of
      gene activation by NRs through chromatin remodeling.

PMID- 16094446
TI  - Epigenetic silencing of the MGMT gene in cancer.
AB  - Silencing of the O6-methylguanine-DNA methyltransferase (MGMT) gene, a key to DNA
      repair, plays a critical role in the development of cancer. The gene product,
      functioning normally, removes a methyl group from mutagenic O6-methylguanine,
      which is produced by alkylating agents and can make a mismatched pair with
      thymine, leading to transition mutation through DNA replication. MGMT is
      epigenetically silenced in various human tumors. It is well known that DNA
      hypermethylation at the promoter CpG island plays a pivotal role in the
      epigenetic silencing of tumor suppressor genes. MGMT silencing, however, occurs
      without DNA hypermethylation in some cancer cells. Dimethylation of histone H3
      lysine 9 and binding of methyl-CpG binding proteins are common and essential in
      MGMT-silenced cells. Silencing of MGMT has been shown to be a poor prognostic
      factor but a good predictive marker for chemotherapy when alkylating agents are
      used. In this review, we describe recent advances in understanding the silencing
      of MGMT and its role in carcinogenesis; epigenetic mechanisms; and clinical
      implications.

PMID- 16094447
TI  - Maintenance and regulation of DNA methylation patterns in mammals.
AB  - Proper establishment and faithful maintenance of epigenetic information is
      crucial for the correct development of complex organisms. For mammals, it is now
      accepted that DNA methylation is an important mechanism for establishing stable
      heritable epigenetic marks. The distribution of methylation in the genome is not
      random, and patterns of methylated and unmethylated DNA are well regulated during
      normal development. The molecular mechanisms by which methylation patterns are
      established and maintained are complex and just beginning to be understood. In
      this review, we summarize recent progress in understanding the regulation of
      mammalian DNA methylation patterns, with an emphasis on the emerging roles of
      several protein and possible RNA factors. We also revisit the stochastic model of
      maintenance methylation and discuss its implications for epigenetic fidelity and
      gene regulation.

PMID- 16094448
TI  - Psoralen photocrosslinking, a tool to study the chromatin structure of RNA
      polymerase I--transcribed ribosomal genes.
AB  - The chromatin structure of RNA polymerase I--transcribed ribosomal DNA (rDNA) is
      well characterized. In most organisms, i.e., lower eukaryotes, plants, and
      animals, only a fraction of ribosomal genes are transcriptionally active. At the
      chromatin level inactive rDNA is assembled into arrays of nucleosomes, whereas
      transcriptionally active rDNA does not contain canonical nucleosomes. To separate
      inactive (nucleosomal) and active (non-nucleosomal) rDNA, the technique of
      psoralen photocrosslinking has been used successfully both in vitro and in vivo.
      In Saccharomyces cerevisiae, the structure of rDNA chromatin has been
      particularly well studied during transcription and during DNA replication. Thus,
      the yeast rDNA locus has become a good model system to study the interplay of all
      nuclear DNA processes and chromatin. In this review we focused on the studies of
      chromatin in ribosomal genes and how these results have helped to address the
      fundamental question: What is the structure of chromatin in the coding regions of
      genes?

PMID- 16094449
TI  - Cross-talking histones: implications for the regulation of gene expression and
      DNA repair.
AB  - The regulation of chromatin structure is essential to life. In eukaryotic
      organisms, several classes of protein exist that can modify chromatin structure
      either through ATP-dependent remodeling or through the post-translational
      modification of histone proteins. A vast array of processes ranging from
      transcriptional regulation to DNA repair rely on these histone-modifying enzymes.
      In the last few years, enzymes involved in the post-translational modification of
      histone proteins have become a topic of intense interest. Our work and the work
      of several other laboratories has focused largely on understanding the biological
      role of the yeast histone methyltransferase COMPASS (complex of proteins
      associated with Set1) and its human homologue the MLL complex. The Set1
      containing complex COMPASS acts as the sole histone H3 lysine 4 methyltransferase
      in Saccharomyces cerevisiae, and this methyl mark is important for
      transcriptional regulation and silencing at the telomeres and rDNA loci. Another
      histone methyltransferase, Dot1, methylates lysine 79 of histone H3 and is also
      essential for proper silencing of genes near telomeres, the rDNA loci, and the
      mating type loci. Employing our global biochemical screen GPS (global proteomic
      analysis of S. cerevisiae) we have been successful in identifying and
      characterizing several key downstream and upstream regulators of both COMPASS and
      Dot1 histone methyltransferase activity. This review details efforts made towards
      understanding the regulatory mechanisms and biological significance of COMPASS
      and Dot1p-mediated histone methylation.

PMID- 16094450
TI  - How does the histone code work?
AB  - Patterns of histone post-translational modifications correlate with distinct
      chromosomal states that regulate access to DNA, leading to the histone-code
      hypothesis. However, it is not clear how modification of flexible histone tails
      leads to changes in nucleosome dynamics and, thus, chromatin structure. The
      recent discovery that, like the flexible histone tails, the structured globular
      domain of the nucleosome core particle is also extensively modified adds a new
      and exciting dimension to the histone-code hypothesis, and calls for the re
      examination of current models for the epigenetic regulation of chromatin
      structure. Here, we review these findings and other recent studies that suggest
      the structured globular domain of the nucleosome core particle plays a key role
      regulating chromatin dynamics.

PMID- 16094451
TI  - Euchromatic and heterochromatic domains at Drosophila telomeres.
AB  - Noncoding repetitive sequences make up a large portion of eukaryotic genomes, but
      their function is not well understood. Large blocks of repetitive DNA-forming
      heterochromatin around the centromeres are required for this region to function
      properly, but are difficult to analyze. The smaller regions of heterochromatin at
      the telomeres provide an opportunity to study their DNA and protein composition.
      Drosophila telomere length is maintained through the targeted transposition of
      specific non-long terminal repeat retrotransposons to chromosome ends, where they
      form long tandem arrays. A subterminal telomere-associated sequence (TAS) lies
      immediately proximal to the terminal-retrotransposon array. Here, we review the
      experimental support for the heterochromatic features of Drosophila telomeres,
      and provide evidence that telomeric regions contain 2 distinct chromatin
      subdomains: TAS, which exhibits features that resemble beta heterochromatin; and
      the terminal array of retrotransposons, which appears euchromatic. This
      organization is significantly different from the telomeric organization of other
      eukaryotes, where the terminal telomerase-generated repeats are often folded in a
      t-loop structure and become part of the heterochromatin protein complex.

PMID- 16094452
TI  - NTP-driven translocation and regulation of downstream template opening by multi
      subunit RNA polymerases.
AB  - Multi-subunit RNA polymerases bind nucleotide triphosphate (NTP) substrates in
      the pretranslocated state and carry the dNMP-NTP base pair into the active site
      for phosphoryl transfer. NTP-driven translocation requires that NTP substrates
      enter the main-enzyme channel before loading into the active site. Based on this
      model, a new view of fidelity and efficiency of RNA synthesis is proposed. The
      model predicts that, during processive elongation, NTP-driven translocation is
      coupled to a protein conformational change that allows pyrophosphate release:
      coupling the end of one bond-addition cycle to substrate loading and
      translocation for the next. We present a detailed model of the RNA polymerase II
      elongation complex based on 2 low-affinity NTP binding sites located in the main
      enzyme channel. This model posits that NTP substrates, elongation factors, and
      the conserved Rpb2 subunit fork loop 2 cooperate to regulate opening of the
      downstream transcription bubble.

PMID- 16094454
TI  - H2AX: tailoring histone H2A for chromatin-dependent genomic integrity.
AB  - During the last decade, chromatin research has been focusing on the role of
      histone variability as a modulator of chromatin structure and function. Histone
      variability can be the result of either post-translational modifications or
      intrinsic variation at the primary structure level: histone variants. In this
      review, we center our attention on one of the most extensively characterized of
      such histone variants in recent years, histone H2AX. The molecular phylogeny of
      this variant seems to have run in parallel with that of the major canonical
      somatic H2A1 in eukaryotes. Functionally, H2AX appears to be mainly associated
      with maintaining the genome integrity by participating in the repair of the
      double-stranded DNA breaks exogenously introduced by environmental damage
      (ionizing radiation, chemicals) or in the process of homologous recombination
      during meiosis. At the structural level, these processes involve the
      phosphorylation of serine at the SQE motif, which is present at the very end of
      the C-terminal domain of H2AX, and possibly other PTMs, some of which have
      recently started to be defined. We discuss a model to account for how these H2AX
      PTMs in conjunction with chromatin remodeling complexes (such as INO80 and SWRI)
      can modify chromatin structure (remodeling) to support the DNA unraveling
      ultimately required for DNA repair.

PMID- 16094453
TI  - Functional dissection of the catalytic mechanism of mammalian RNA polymerase II.
AB  - High resolution X-ray crystal structures of multisubunit RNA polymerases (RNAP)
      have contributed to our understanding of transcriptional mechanisms. They also
      provided a powerful guide for the design of experiments aimed at further
      characterizing the molecular stages of the transcription reaction. Our laboratory
      used tandem-affinity peptide purification in native conditions to isolate human
      RNAP II variants that had site-specific mutations in structural elements located
      strategically within the enzyme's catalytic center. Both in vitro and in vivo
      analyses of these mutants revealed novel features of the catalytic mechanisms
      involving this enzyme.

PMID- 16094455
TI  - Organizing the genome: enhancers and insulators.
AB  - Enhancers can activate their target genes over large linear distances. Insulators
      can delimit the influence of an enhancer to an appropriate target. There are a
      number of intertwined mechanisms by which the regulatory functions of enhancers
      and insulators might be carried out at the level of the chromatin fiber. Recent
      evidence suggests that both enhancers and insulators participate in higher-order
      organization of chromatin in the nucleus and in localization of their regulated
      sequences to both subnuclear structures and compartments. Novel experimental
      approaches are helping to reveal the mechanisms underlying nuclear organization
      of developmentally regulated genes.

PMID- 16094456
TI  - Tilling the chromatin landscape: emerging methods for the discovery and profiling
      of protein-DNA interactions.
AB  - Interactions between protein and DNA are essential for cellular function. The
      incremental process of developing global approaches to study chromatin began with
      the in vitro characterization of chromatin structural components and
      modifications of the versatile chromatin immunoprecipitation (ChIP) assay,
      capable of analyzing protein-DNA interactions in vivo. Among the emerging global
      approaches are ChIP cloning, ChIP display, differential chromatin scanning, ChIP
      chip, DamID chromatin profiling, and chromatin array. These methods have been
      used to assess transcription-factor binding and (or) histone modification. This
      review describes these global methods and illustrates their potential in
      answering biological questions.

PMID- 16094457
TI  - Subnuclear compartmentalization of sequence-specific transcription factors and
      regulation of eukaryotic gene expression.
AB  - To date, the majority of the research regarding eukaryotic transcription factors
      has focused on characterizing their function primarily through in vitro methods.
      These studies have revealed that transcription factors are essentially modular
      structures, containing separate regions that participate in such activities as
      DNA binding, protein-protein interaction, and transcriptional activation or
      repression. To fully comprehend the behavior of a given transcription factor,
      however, these domains must be analyzed in the context of the entire protein, and
      in certain cases the context of a multiprotein complex. Furthermore, it must be
      appreciated that transcription factors function in the nucleus, where they must
      contend with a variety of factors, including the nuclear architecture, chromatin
      domains, chromosome territories, and cell-cycle-associated processes. Recent
      examinations of transcription factors in the nucleus have clarified the behavior
      of these proteins in vivo and have increased our understanding of how gene
      expression is regulated in eukaryotes. Here, we review the current knowledge
      regarding sequence-specific transcription factor compartmentalization within the
      nucleus and discuss its impact on the regulation of such processes as activation
      or repression of gene expression and interaction with coregulatory factors.

PMID- 16094458
TI  - Lsh, a guardian of heterochromatin at repeat elements.
AB  - Lymphoid-specific helicase (Lsh) is a crucial factor for normal embryonic
      development; targeted deletion of Lsh is lethal. Lsh belongs to a family of
      chromatin-remodeling proteins and is closely associated with pericentromeric
      heterochromatin. Lsh deficiency leads to abnormal heterochromatin organization,
      with a loss of DNA methylation, and an altered pattern of histone-tail
      acetylation and methylation. As a functional consequence of perturbed
      heterochromatin, aberrant reactivation of parasitic retroviral elements in the
      genome and abnormal mitosis with amplified centrosomes and genomic instability
      were observed. Thus, Lsh is a major epigenetic regulator crucial for normal
      heterochromatin structure and function.

PMID- 16094459
TI  - Chromatin potentiation of the hsp70 promoter is linked to GAGA-factor
      recruitment.
AB  - The events leading to transcription initiation of the Drosophila melanogaster
      heat-shock protein (hsp)70 gene have been demonstrated to be directly connected
      with nucleosome remodeling factor and GAGA-dependent chromatin remodeling on its
      promoter region. To investigate the relative importance of the multiple GAGA
      factor binding sites in the process of chromatin remodeling and their effect on
      DNA conformation, the position of nucleosomes over the proximal region of the
      promoter was mapped. No real-positioned nucleosome was detected. By matching the
      relative position of the GAGA-factor binding sites with the distribution of
      nucleosomes over the hsp70 promoter, the GAGA site 2 appeared to be the most
      accessible, i.e., located close to a nucleosomal edge or within the linker DNA.
      This result, combined with previous observations, suggest a link between
      increased GAGA-factor accessibility and efficiency of transcription initiation.
      The effect of GAGA-binding-site mutations, both individually and in combination,
      on DNA structure and nucleosome remodeling was assessed using free DNA and fly
      embryo extract chromatin templates assembled in vitro. Results indicated that
      both the number of functional sites and their positions within the chromatin were
      important determinants for nucleosome-remodeling efficiency. Ultimately, the
      degree of accessibility of the GAGA factor to its cognate binding site(s) appears
      to be proportional to chromatin-remodeling competency of the hsp70 promoter.

PMID- 16094461
TI  - Plasmodium species mixed infections in two areas of Manhica district, Mozambique.
AB  - We compared the distribution patterns of individual Plasmodium species and mixed
      species infections in two geographically close endemic areas, but showing
      environmental differences. Comparisons concerned circulating Plasmodium
      infections in both human and mosquito vector populations in the dry and wet
      seasons, at a micro-epidemiological level (households). Both areas revealed a
      very high overall prevalence of infection, all year-round and in all age groups.
      Plasmodium falciparum was the predominant species, being found in the vast
      majority of infected individuals regardless of the presence of other species.
      Plasmodium malariae and Plasmodium ovale occurred almost exclusively in mixed
      infections. Seasonal variation in P. malariae prevalence was observed in one area
      but not in the other. A decrease in P. malariae prevalence concurred with a
      marked increase of P. falciparum prevalence. However this was strongly dependent
      on age and when analysing infections at the individual level, a different pattern
      between co-infecting species was unveiled. Regarding transmission patterns, in
      both areas, P. falciparum gametocytes predominated in single infections
      regardless of age and P. malariae gametocyte carriage increased when its overall
      prevalence decreased.

PMID- 16094462
TI  - SDS-PAGE electrophoretic property of human chorionic gonadotropin (hCG) and its
      beta-subunit.
AB  - The microheterogeneity property of hCG with regards to its sialic acid contents
      resulted in variable mobility of the glycoprotein in SDS-PAGE. The intact hCG
      molecule is composed of two dissimilar subunits, namely alpha- and beta-subunits.
      The identification of hCG bands in SDS-PAGE was accomplished by the
      immunoblotting experiment, whereby the antibody directed toward the specific
      region of beta-subunit of hCG was used. The data shows that the different
      mobility of intact hCG was attributed to the different degree of desialylation of
      the glycoprotein. Nevertheless, unlike the intact hCG, the mobility of its beta
      subunit was not affected by its variety sialic acid content. This characteristic
      of beta-hCG is beneficial when semi-quantification of total hCG is required.
      Quantification of hCG using the HPLC-reversed phase C18 analytical column is not
      possible as the glycoprotein was eluted in multiple fractions at different
      retention times. The identification of denatured hCG (HPLC eluted fractions) was
      carried out by immunoblotting experiment whilst immunoassay technique failed to
      detect its presence in any fraction.

PMID- 16094463
TI  - Translocation of a 190-kb mitochondrial fragment into rice chromosome 12 followed
      by the integration of four retrotransposons.
AB  - A 190-kb mitochondrial DNA sequence interrupted by seven foreign DNA segments was
      identified in rice chromosome 12. This fragment is the largest mitochondrial
      fragment translocated into the rice nuclear genome. The sequence is composed of a
      190-kb segment of mitochondrial origin corresponding to 38.79% of the
      mitochondrial genome, 45 kb comprising four segments of retrotransposon origin,
      and 13 kb comprising three segments of unknown origin. The 190-kb sequence shows
      more than 99.68% similarity to the current mitochondrial sequence, suggesting
      that its integration into the nucleus was quite recent. Several sequences in the
      190-kb segment have been rearranged relative to the current mitochondrial
      sequence, suggesting that the past and present arrangements of the mitochondrial
      genome differ. The four retrotransposons show no mutual sequence similarity and
      are integrated into different locations, suggesting that their integration events
      were independent, frequent, and quite recent. A fragment of the mitochondrial
      genome present in the nuclear genome, such as the 248-kb sequence characterized
      in this study, is a good relic with which to investigate the past mitochondrial
      genome structure and the behavior of independent retrotransposons during
      evolution.

PMID- 16094464
TI  - Purification, properties and alternate substrate specificities of arginase from
      two different sources: Vigna catjang cotyledon and buffalo liver.
AB  - Arginase was purified from Vigna catjang cotyledons and buffalo liver by
      chromatographic separations using Bio-Gel P-150, DEAE-cellulose and arginine AH
      Sepharose 4B affinity columns. The native molecular weight of an enzyme estimated
      on Bio-Gel P-300 column for Vigna catjang was 210 kDa and 120 kDa of buffalo
      liver, while SDS-PAGE showed a single band of molecular weight 52 kDa for
      cotyledon and 43 kDa for buffalo liver arginase. The kinetic properties
      determined for the purified cotyledon and liver arginase showed an optimum pH of
      10.0 and pH 9.2 respectively. Optimal cofactor Mn(++) ion concentration was found
      to be 0.6 mM for cotyledon and 2 mM for liver arginase. The Michaelis-Menten
      constant for cotyledon arginase and hepatic arginase were found to be 42 mM and 2
      mM respectively. The activity of guanidino compounds as alternate substrates for
      Vigna catjang cotyledon and buffalo liver arginase is critically dependent on the
      length of the amino acid side chain and the number of carbon atoms. In addition
      to L-arginine cotyledon arginase showed substrate specificity towards agmatine
      and L-canavanine, whereas the liver arginase showed substrate specificity towards
      only L-canavanine.

PMID- 16094465
TI  - A new way of describing meiosis that uses fractal dimension to predict metaphase
      I.
AB  - Meiosis, the reductive nuclear division, is a continuum, but for purposes of
      communication, is described in stages. In sexually-reproducing organisms,
      including the dwarf mistletoe Arceuthobium americanum, prophase I of meiosis is
      prolonged (8 months for female A. americanum). Conversely, metaphase I, where
      chromosome pairs line up along a dividing cell's "equator", is relatively brief,
      difficult to predict, but critical regarding the random distribution of the
      paternal and maternal chromosomes in sexual organisms. However, descriptions of
      meiosis as either a continuum or stages are limited to qualitative observations.
      A quantification of meiosis can provide mathematical descriptors and allow for
      the prediction of when chromosomes reach the equator; this will not only be
      useful to researchers of cell division, but also to those requiring a large
      sample of metaphase I materials. Here, the probability-density function was used
      to calculate the fractal dimension of A. americanum nuclei undergoing early
      meiosis, and it predicted the onset of metaphase I by 2 days.

PMID- 16094466
TI  - Dalton transactions: at the 'frontier' of inorganic chemistry.

PMID- 16094467
TI  - Metal complexes in molecular electronics: progress and possibilities.
AB  - A selective summary of some of the issues surrounding the development of a
      molecular-based electronics technology is presented, highlighting the
      characteristics of metal complexes that make these species particularly
      attractive for the construction of highly integrated, functional molecular
      components.

PMID- 16094468
TI  - A highly water-soluble platinum(ii) complex containing a thiopropyl-1,2-dicarba
      closo-dodecaborane(12) ligand functionalised with a pendant glycerol group.
AB  - Reaction of the novel thiopropyl-closo-1,2-carborane ligand bearing a pendant
      glycerol group HS(CH(2))(3)CB(10)H(10)CCH(2)OCH(CH(2)OH)(2)(L) with the labile
      platinum(ii) precursor [Pt(MeCN)(terpy)](OTf)(2)(terpy = 2,2':6',2''-terpyridine;
      OTf = trifluoromethanesulfonate) affords the highly water-soluble platinum(ii)
      complex [PtL(terpy)]OTf, the first example of a metal-carborane complex
      functionalised with a water-solubilising glycerol group.

PMID- 16094469
TI  - Synthesis and anti-cancer activity of dinuclear platinum(II) complexes containing
      bis(thioalkyl)dicarba-closo-dodecaborane(12) ligands.
AB  - A series of novel, dinuclear (2,2':6',2''-terpyridine)platinum(ii) complexes
      containing bis(thioalkyl)-dicarba-closo-dodecaborane(12)(carborane) ligands were
      prepared and characterised, and their preliminary anti-cancer characteristics
      have been determined in vitro; the complexes are the first examples of bis
      intercalator complexes containing a boron-rich carborane cage.

PMID- 16094470
TI  - The first example of a hetero-tetranuclear [(VO)Gd](2) complex: synthesis,
      crystal structure and magnetic properties of
      [VOLGd(hfa)(2)CH(3)OH](2).2CH(3)OH.2(CH(3))(2)CO.
AB  - A cyclic tetranuclear [V(IV)O-Gd(III)](2) complex with VO and Gd ions alternately
      arrayed, behaves, from the magnetic point of view, as two independent dinuclear
      entities each having a S= 4 ground state, as a consequence of an active and
      ferromagnetic VO-Gd interaction through the double phenoxo bridge and a
      magnetically inactive VO-Gd interaction through the amide bridge.

PMID- 16094471
TI  - Lithium and aluminium complexes supported by chelating phosphaguanidinates.
AB  - Diisopropylcarbodiimide, (i)PrN[double bond, length as m-dash]C[double bond,
      length as m-dash]N(i)Pr, inserts into the lithium-phosphorus bond of in situ
      prepared "Ph(2)PLi(THF)(n)" to afford the lithium salt,
      [Li(Ph(2)PC{N(i)Pr}(2))(THF)(n)](x)(2a); alternatively, this compound can be made
      by deprotonation of the neutral phosphaguanidine, Ph(2)PC{N(i)Pr}{NH(i)Pr}(1a)
      with (n)BuLi. Displacement of the THF solvate in 2a is readily achieved with
      TMEDA to afford Li(Ph(2)PC{N(i)Pr}(2))(TMEDA)(3a). X-Ray crystallographic
      analyses show that 2a exists as a dimer in the solid state with a folded ladder
      structure and an N,N' chelating phosphaguanidinate, while 3a is monomeric with
      N,P-coordination of the ligand to lithium. Compound 2a reacts via a
      transmetallation pathway with AlMe(2)Cl to afford the dimethylaluminium complex,
      Al(Ph(2)PC{N(i)Pr}(2))Me(2)(4a), which can also be prepared by protonation of a
      methyl group of AlMe(3) using 1a. The formation of a series of dialkylaluminium
      compounds has been investigated employing this latter pathway using both 1a and
      the N,N'-dicyclohexyl analogue, Ph(2)PC{NCy}{NHCy}(1b), affording
      Al(Ph(2)PC{NR}(2))Et(2)(5a,b), Al(Ph(2)PC{NR}(2))(i)Bu(2)(6a,b) and the
      diphenylaluminium compound Al(Ph(2)PC{N(i)Pr}(2))Ph(2)(7a). The oily nature of
      most of the dialkyl compounds and high sensitivity to oxygen and moisture lead to
      difficulty in manipulation and characterization; however, NMR spectroscopy
      indicated highly pure products (>95%) upon removal of the solvent. The molecular
      structures of the crystalline examples 4a and 7a are reported, showing monomeric
      aluminium species with symmetrically chelating phosphaguanidinate ligands. The
      series of aluminium compounds AlLCl(2){L=[EC{NiPr}(2)](-): A, E=Me; B, E=Me(2)N;
      C, E=(Me(3)Si)(2)N and D, E=Ph(2)P} were investigated using density functional
      theory. In the more simple cases A and B, the delocalized electron density of the
      metallacycle was represented by a combination of the HOMO and an orbital of lower
      energy (A, HOMO-5; B, HOMO-6). The HOMO-1 in B was pi-bonded across the Me(2)N-C
      bond suggesting delocalization of electron density into the metallacycle. In the
      more complex systems C and D, delocalization within the metallacycle was less
      extensive due to the (Me(3)Si)(2)N- and Ph(2)P-moieties. A number of occupied
      orbitals in D, however, display phosphorus 'lone-pair' characteristics,
      indicating that these species have the potential to behave as Lewis bases in the
      formation of poly(metallic) systems.

PMID- 16094472
TI  - Synthesis, characterization and electrochemical studies of mixed ligand complexes
      of ruthenium(ii) with DNA.
AB  - Two mixed ligand complexes of ruthenium(ii) [Ru(bzimpy)(bpy)(OH(2))](2+) (1) and
      [Ru(bzimpy)(phen)(OH(2))](2+) (2) have been synthesized and characterized by FAB
      mass, (1)H NMR, cyclic voltammetry and spectroelectrochemical measurements.
      Controlled potential electrolysis of these complexes results in the conversion of
      ruthenium(ii) to ruthenium(iii) at 0.6 V and ruthenium(iii) to ruthenium(iv) at
      0.8 V vs. SCE. The binding constant of these complexes with DNA has been
      determined electrochemically and found to be (3.58 +/- 0.25) x 10(4) and (2.87+/-
      0.2) x 10(4) M(-1). Viscosity measurements suggest that these complexes bind with
      DNA through intercalation. Such intercalative binding to DNA has been found to
      induce chirality to the two complexes. Electrochemically generated ruthenium(iv)
      species of these complexes have been found to bring about oxidative cleavage in
      DNA.

PMID- 16094473
TI  - Substituent effects and the mechanism of alkene metathesis catalyzed by ruthenium
      dichloride catalysts.
AB  - Density functional theory calculations are reported concerning the dissociative
      mechanism for alkene metathesis by ruthenium dichloride catalysts, including both
      bisphosphine and diaminocarbene/phosphine complexes. The calculations use a
      hierarchy of models, ranging from [(L)(PH(3))Ru(Cl)(2)(CH(2))](L=PH(3) or
      diaminocarbene) through the larger [(L)(PMe(3))Ru(Cl)(2)(CHPh)] to the
      "real"[(L)(PCy(3))Ru(Cl)(2)(CHPh)]. Calculations show that the rate-limiting step
      for metathesis is either ring closing from an alkene complex to form a ruthena
      cyclobutane, or ring-opening of the latter intermediate to form an isomeric
      alkene complex. The higher efficiency of the diaminocarbene based catalysts is
      due to the stabilization of the formal +iv oxidation state of the ruthenium
      centre in the metallacycle. This effect is partly masked in the smaller model
      systems due to a previously unnoticed stereoelectronic effect. The calculations
      do not reproduce the experimental observation whereby the initiation step,
      phosphine dissociation, is more energetically demanding and hence slower for the
      diaminocarbene-containing catalyst system than for the bisphosphine. Further
      calculations on the corresponding bond energies using a variety of DFT and hybrid
      DFT/molecular mechanics methods all find instead a larger phosphine dissociation
      energy for the bisphosphine catalyst. This reversed order of binding energies
      would in fact be the one expected based on the stronger trans influence of the
      diaminocarbene ligand. The discrepancy with experiment is small and could have a
      number of causes which are discussed here.

PMID- 16094474
TI  - Structure, reactivity and solution behaviour of [Re(ser)(7-MeG)(CO)(3)] and
      [Re(ser)(3-pic)(CO)(3)]: "nucleoside-mimicking" complexes based on the fac
      [Re(CO)(3)](+) moiety.
AB  - The fac-[Re(CO)(3)](+) moiety was reacted with the amino acid serine (D- and L
      ser) and with 7-methylguanine (7-MeG), 3-methylpyridine (3-pic) or adenine (ade)
      to yield novel complexes intended as nucleoside-mimicking compounds. Reaction of
      [Re(H(2)O)(3)(CO)(3)](+)(1) with L-ser yields the complex [Re(L-ser)(2)(CO)(3)](L
      2). X-Ray structure analysis of L-2 reveals that one of the two amino acids is
      bound to the metal centre in a bidentate fashion while the other amino acid is
      bound as a zwitterion via the carboxylate oxygen only. Reaction of L-2 and of
      [Re(D-ser)(2)(CO)(3)](D-2) with 7-MeG yields complexes [Re(L-ser)(7
      MeG)(CO)(3)](L-3) and [Re(D-ser)(7-MeG)(CO)(3)](D-3) respectively. Complexes L-3
      and D-3 are received as a mixture of diastereomers. If 3-pic is used instead of 7
      MeG complex [Re(L-ser)(3-pic)(CO)(3)](L-4) is obtained in good yield, while
      interaction of L-2 with ade gives a mixture of five distinct species.
      Crystallization gave one single diastereomer for L-3 and D-3 and the two forms
      for 4 respectively. X-Ray structure analyses reveal that in all cases the amino
      acid is bound in a chelate fashion with the base occupying the sixth co
      ordination site. When crystals of either 2 or 3 are dissolved in a CD(3)OD/D(2)O
      mixture (1:1, 293 K) rapid transformation to the diastereomeric mixture is
      observed. While for L-2 this reorganisation is fast on the NMR time scale even at
      193 K, the rate constant for the rearrangement of L-3 and D-3 is 1.36 +/- 0.24 x
      10(-2) s(-1) at 293 K.

PMID- 16094475
TI  - Syntheses and reactivity of 'sulfur rich' Re(iii) and Tc(iii) complexes
      containing trithioperoxybenzoate, dithiobenzoate and dithiocarbamate ligands.
AB  - Reduction-substitution reactions of [M(O)Cl(4)](-)(M=Re, (99)Tc) precursors with
      an excess of substituted dithiobenzoate ligands (R-PhCS(2))(-) in
      dichloromethane/methanol mixtures afford a series of six-coordinated neutral
      mixed-ligand complexes of the type M(III)(R-PhCS(3))(2)(R-PhCS(2))(M=Re; Rel--9;
      M=99)Tc; Tel--9). The coordination sphere is entirely filled by sulfur donor
      atoms, and the complexes adopt a distorted trigonal prismatic arrangement, as
      assessed by the X-ray crystal structure analysis of Re(4-Me-PhCS(3))(2)(4-Me
      PhCS(2)), Re 2. These compounds show sharp proton and carbon NMR profiles, in
      agreement with the diamagnetism typical of low spin d(4) trigonal prismatic
      configurations. The red-ox processes involve reduction of the metal from Re(v) to
      Re(iii) and oxidation of dithiobenzoate to trithioperoxybenzoate. M2--9 complexes
      contain a substitution-inert [M(R-PhCS(3))(2)](+) moiety including the metal and
      two trithioperoxybenzoate fragments, while the third dithiobenzoate ligand is
      labile. The latter is efficiently replaced by reaction with better nucleophiles
      such as diethyldithiocarbamate giving a further class of mixed ligand complexes
      of the type M(III)(R-PhCS(3))(2)(Et(2)NCS(2))(M=Re; Re 10--18; M=(99)Tc; Tc--18),
      which retain the trigonal prismatic arrangement, as determined by the X-ray
      analyses of the representative compounds Re(PhCS(3))(2)(Et(2)NCS(2)), Re 10 and
      (99)Tc(PhCS(3))(2)(Et(2)NCS(2)), Tc 10.

PMID- 16094476
TI  - Copper-ion interaction with the 106-113 domain of the prion protein: a solution
      equilibria study on model peptides.
AB  - Prion diseases are characterized by a structural modification of the regular
      prion protein (PrP(C)) to its isoform, termed PrP(Sc)(scrapie). Such a
      modification involves the secondary and tertiary structure of the protein; the
      amino acidic sequence remains unchanged. PrP(Sc) is almost insoluble in non
      denaturing solvents, resistant to proteases and it loses its redox activity.
      PrP(C) is able to bind copper and other metal ions: these complexes have been
      suggested to play an important role in the protein refolding leading to PrP(Sc).
      It is well-known that at least one relatively strong copper-binding site is
      located in the PrP(92--126) domain, where two His residues (96 and 111) are
      present. However, in the same domain, other amino acidic residues bear
      potentially donating atoms, i.e. Met, Asn and Lys residues. In order to shed
      light on the role of the side chains of such potentially tridentate amino acids
      on copper complexation, the polypeptide Ac-KTNMKHMA-NH(2), corresponding to the
      PrP(106--113) fragment, and some synthetic analogues have been investigated as
      ligands for the copper ion, by means of both thermodynamic and spectroscopic
      techniques. The pivotal role of imidazolic side chain of His in "anchoring" the
      metal ion has been confirmed. On the other hand, no clue was found on the
      participation of sulfur atom of Met or side amino-group of Lys residues to copper
      complex-formation.

PMID- 16094477
TI  - Structure and properties of bivalent nickel and copper complexes with pyrazine
      amide-thioether coordination: stabilization of trivalent nickel.
AB  - Acyclic pyrazine-2-carboxamide and thioether containing hexadentate ligand 1,4
      bis[o-(pyrazine-2-carboxamidophenyl)]-1,4-dithiobutane (H(2)bpzctb), in its
      deprotonated form, has afforded light brown [Ni(II)(bpzctb)](1)(S=1) and green
      [Cu(II)(bpzctb)](2)(S=1/2) complexes. The crystal structures of 1.CH(3)OH and
      2.CH(2)Cl(2) revealed that in these complexes the ligand coordinates in a
      hexadentate mode, affording examples of distorted octahedral
      M(II)N(2)(pyrazine)N'(2)(amide)S(2)(thioether) coordination. Each complex
      exhibits in CH(2)Cl(2) a reversible to quasireversible cyclic voltammetric
      response, corresponding to the Ni(III)/Ni(II)(1) and Cu(II)/Cu(I)(2) redox
      process. The E(1/2) values reveal that the complexes of bpzctb(2-) are uniformly
      more anodic by approximately 0.2 V than those of the corresponding complexes with
      the analogous pyridine ligand, 1,4-bis[o-(pyridine-2-carboxamidophenyl)]-1,4
      dithiobutane (H(2)bpctb), attesting that compared to pyridine, pyrazine is a
      better stabilizer of the Ni(ii) or Cu(i) state. Coulometric oxidation of the
      previously reported complex [Ni(II)(bpctb)] and 1 generates [Ni(III)(bpctb)](+)
      and [Ni(III)(bpzctb)](+) species, which exhibit a LMCT transition in the 470--480
      nm region and axial EPR spectra corresponding to a tetragonally elongated
      octahedral geometry. Complex 2 exhibits EPR spectra characteristic of the d(z(2))
      ground state.

PMID- 16094478
TI  - A 1,8-naphthalenediol-based unsymmetrical dinucleating ligand.
AB  - A facile synthesis of 2-formyl-1,8-naphthalenediol is reported. Its potential as
      a general precursor for the preparation of unsymmetrical multidentate chelating
      ligand systems based on 1,8-naphthalenediol is demonstrated by the synthesis of
      the dinucleating ligand L(4-)(H(4)L=N,N'-bis(2-(1,8
      naphthalenediol)methylidene)propylenediamine). Reaction of H(4) L with copper
      acetate results in the formation of the unsymmetrical dinuclear Cu(II) complex
      [LCu(2)](3), which has been structurally characterized by single-crystal X-ray
      diffraction. One Cu(II) ion is coordinated by a N(2)O(2) compartment of L(4-) and
      the other Cu(II) ion is coordinated by an O(4) compartment of L(4-) while they
      are bridged by two aryloxide functions of L(4-). A dimerization of two molecules
      of 3 to a tetranuclear entity 3(2) occurs through formation of weak apical Cu--O
      interactions. Analysis of the temperature dependent magnetic susceptibility
      measurements (2--290 K) established a strong intradimer exchange coupling J(12)=
      371 cm(-1). This strong superexchange interaction fits nicely in a magneto
      structural correlation which has been established for dinuclear bis(phenoxide)
      bridged Cu(II) complexes demonstrating the electronic equivalence of the
      aryloxides of a phenol and 1,8-naphthalenediol.

PMID- 16094479
TI  - Self-assembly of copper(ii) complexes with ladder, bi-rack, rack--ladder--rack
      and layer structures by the directional-bonding approach using a T-shaped ligand.
AB  - Six copper(ii) complexes of trans-1,2,3-propenetricarboxylic acid (H(3)L) with
      novel ladder, bi-rack, rack-ladder-rack and layer structures were obtained by the
      combination of the diverse coordination symmetries and the Jahn-Teller effect of
      the Cu(2+) ion and the T-shaped coordination mode of the L(3-) or HL(2-) ligand
      together with the introduction of an inert directing ligand. Solid-state
      photoluminescent analyses of the present compounds show that they display blue
      emissions.

PMID- 16094480
TI  - Cyclam (1,4,8,11-tetraazacyclotetradecane) with one methylphosphonate pendant
      arm: a new ligand for selective copper(ii) binding.
AB  - The new ligand, [(1,4,8,11-tetraazacyclotetradecan-1-yl)methyl]phosphonic acid
      (H(2)te1P, H(2)L), was synthesized and its complexing properties towards selected
      metal ions were studied potentiometrically. The ligand forms a very stable
      complex with copper(ii)(logbeta(CuL)= 27.34), with a high selectivity over
      binding of other metal ions (i.e. logbeta(ZnL)= 21.03). The crystal structures of
      the free ligand (in its protonated form with bromide as counter-ion) and two
      copper(ii) complexes (obtained by crystallization at various pH) were determined.
      The free ligand adopts the common conformation for such macrocycles with the
      protonated nitrogen atoms in the corners of a virtual rectangle. In the trans
      Br,O-[Cu(Br)(Hte1P)].H(2)O species, the central metal ion is surrounded by four
      in plane nitrogen atoms, one oxygen atom of the pendant moiety in the apical
      position and a bromide anion positioned trans to the oxygen atom, forming a
      distorted octahedral coordination sphere. In the compound
      [Cu(H(2)te1P)][Cu(Hte1P)]Br(3).6H(2)O, obtained from a highly acidic solution,
      the bromide anions are placed further away from the copper(ii) ion and the
      coordination environment (N(4)O) is thus square-pyramidal. In both structures,
      the protons are associated with non-coordinated phosphonate oxygen atoms.

PMID- 16094481
TI  - First metallamacrocyclic complexes of Pt(iv) with 3,3,3',3'-tetraalkyl-1,1'
      phenylenedicarbonylbis(thioureas): synthesis by direct or electrolytic oxidative
      addition of I(2), Br(2) and Cl(2).
AB  - Elemental I(2) and Br(2) cleanly react with the 3:3 Pt(ii) metallamacrocycle of
      3,3,3',3'-tetra(n-butyl)-1,1'-terephthaloylbis(thiourea)(cis-[Pt(II)(3)(L(p)(1)
      S,O)(3)]3), in chloroform at room temperature, to yield oxidative addition
      products; (195)Pt NMR studies reveal that a stepwise oxidative addition readily
      occurs to each of the Pt(ii) centres in the metallamacrocycle to yield the mixed
      valence species cis-[Pt(II)(2)Pt(IV)I(2)(L(p)(1)-S,O)(3)] and cis
      [Pt(II)Pt(IV)(2)I(4)(L(p)(1)-S,O)(3)], and the fully oxidised cis
      [Pt(IV)(3)I(6)(L(p)(1)-S,O)(3)] in solution, depending on the mole ratio I(2):3.
      Similar results are obtained on treatment of solutions of 3 with elemental Br(2).
      Treatment of the corresponding 2:2 Pt(ii) complex of 3,3,3',3'-tetraethyl-1,1'
      isophthaloylbis(thiourea)(cis-[Pt(II)(2)(L(m)(1)-S,O)(2)]4) with iodine, results
      in facile oxidative addition to yield cis-[Pt(IV)(2)(L(m)(1)-S,O)(2)I(4)], with a
      trans-Pt(iv)-iodo arrangement. Molecules in the crystal structure of 5 have their
      trans-Pt(iv)-iodo axes essentially aligned, with very close intermolecular iodide
      contacts (3.775(1)A), resulting in chains of weakly bound metallamacrocycles in
      the solid. An alternative electrolytic synthesis method, using a simple two
      compartment glass cell containing 4 and a chosen halide salt in dichloromethane,
      led to the formation of cis-[Pt(IV)(2)(L(m)(1)-S,O)(2)Br(4)] 6 and cis
      [Pt(IV)(2)(L(m)(1)-S,O)(2)Cl(4)] 7, completing characterization of a series of
      first-reported trans-Pt(iv)-X (X=I, Br, Cl) metallamacrocyclic complexes.

PMID- 16094482
TI  - Photophysical properties of binuclear ruthenium(ii) bis(2,2':6',2''-terpyridine)
      complexes built around a central 2,2'-bipyrimidine receptor.
AB  - A binuclear complex has been synthesized having ruthenium(ii) bis(2,2':6',2''
      terpyridine) terminals attached to a central 2,2'-bipyrimidine unit via
      ethynylene groups. Cyclic voltammetry indicates that the substituted terpyridine
      is the most easily reduced subunit and the main chromophore involves charge
      transfer from the metal centre to this ligand. The resultant metal-to-ligand,
      charge-transfer (MLCT) triplet state is weakly emissive and has a lifetime of 60
      ns in deoxygenated solution at room temperature. The luminescence yield and
      lifetime increase with decreasing temperature in a manner that indicates the
      lowest-energy MLCT triplet couples to at least two higher-energy triplets.
      Cations can bind to the central bipyrimidine unit, forming both 1:1 and 1:2
      (ligand:metal) complexes as confirmed by electrospray MS analysis. The
      photophysical properties depend on the number of bound cations and on the nature
      of the cation. In the specific case of binding zinc(ii) cations, the 1:1 complex
      has a triplet lifetime of 8.0 ns while that of the 1:2 complex is 1.8 ns. The 1:1
      complexes formed with Ba(2+) and Mg(2+) are more luminescent than is the parent
      compound while the 1:2 complexes are much less luminescent. It is shown that the
      coordinated cations raise the reduction potential of the central bipyrimidine
      unit and thereby increase the activation energy for coupling with the metal
      centred state. Complexation also introduces a non-emissive intramolecular charge
      transfer (ICT) state that couples to the lowest-energy MLCT triplet and provides
      an additional non-radiative decay route. The triplet state of the 1:2 complex
      formed with added Zn(2+) cations decays preferentially via this ICT state.

PMID- 16094483
TI  - DFT-calculation of the structural isomers of (1-methyl-4-phenyl-1-azabuta-1,3
      diene)tetracarbonyliron(0) and (4-phenyl-1-oxabuta-1,3
      diene)tetracarbonyliron(0).
AB  - DFT calculations (B3LYP/LANL2DZ/6-31 G*) were used to investigate the ways in
      which 1-methyl-4-phenyl-1-azabuta-1,3-diene and 4-phenyl-1-oxabuta-1,3-diene bind
      to a Fe(CO)(4) moiety. As possible coordination modes, eta(2)-coordination across
      the C=C or C=N/C=O bond, sigma-coordination to the lone pair of the heteroatom,
      or eta(3)-coordination through the C=C-C or the N=C-C/O=C-C moiety were
      considered. The latter forms involve coupling of the non-coordinated atom of the
      heterodiene with one of the carbonyl ligands to an acyl species. The calculated
      geometric parameters of all structures compare well with X-ray crystallographic
      data of similar complexes. The species in which the ligand is transoid and sigma
      coordinated is lowest in energy, for both compounds studied. However, the eta(2)
      alkene bound 1-oxabuta-1,3-diene complex is practically equal in energy to the
      sigma-transoid form and thus competes. This agrees with experimental observations
      that the heterodiene is sigma-bonded in Fe(CO)(4)(1-methyl-4-phenyl-1-azabuta-1,3
      diene) but eta(2)-coordinated in Fe(CO)(4)(4-phenyl-1-oxabuta-1,3-diene). The
      solvent dependence was estimated from single point PCM calculations, for
      CH(2)Cl(2) as solvent. For the 1-azabuta-1,3-diene complexes, the relative
      energies of eta(2)-olefin and eta(3)-allyl forms are inverted, with the eta(3)
      allyl form being more stable in polar solvents. The 1-oxabuta-1,3-diene complexes
      in their eta(2)-olefin and sigma-O forms change order of relative energy, and
      conversion to the sigma-O form is expected in a polar medium for these complexes.
      Calculated IR vibrational stretching frequencies of the carbonyl ligands and the
      C[double bond, length as m-dash]N/C[double bond, length as m-dash]O bond were
      compared with experimental data, to produce the best fits for the sigma-transoid
      form of Fe(CO)(4)(1-methyl-4-phenyl-1-azabuta-1,3-diene) and eta(2)-olefin bonded
      Fe(CO)(4)(4-phenyl-1-oxabuta-1,3-diene). These results are again consistent with
      the experiment and show that the DFT method applied in this work can be used as
      an aid for structural validation.

PMID- 16094484
TI  - The assembly of organic radical anions between metal-borate scaffolds.
AB  - Metal-organic frameworks based on the Pb[B(Im)(4)](+) unit form layered
      structures analogous to those observed in clays and double layered hydroxide
      minerals. These layers can act as scaffolds for the organization of anionic
      organic guests. In this report, we use this scaffold to assemble TEMPO and PROXYL
      carboxylates in the interlayer spacings of Pb[B(Im)(4)](4-carboxy-TEMPO) 1 and
      Pb[B(Im)(4)](3-carboxy-PROXYL)(H(2)O)2, respectively. The resultant materials are
      paramagnetic, and the organization of the radical units differs between the two
      compounds. This results in changes in electronic structure of the radical unit,
      as observed by EPR spectroscopy.

PMID- 16094485
TI  - Reactions of a stable silylene with halocarbons.
AB  - An unusual product formation is observed for the insertion reaction of the
      thermally stable silylene Si[(NCH(2)Bu(t))(2)C(6)H(4)-1,2][abbrev. as Si(NN)]
      into the carbon-halogen bond of alkyl or aryl halides RHal (Hal=Cl, Br). In
      general, depending on the halogen, the reaction either results in a disilane of
      type (NN)Si(Hal)-(R)Si(NN) for Hal=Cl or a mixture of disilane and the monosilane
      (NN)Si(R)(Hal) for Hal=Br. The results are put into context to previously
      suggested mechanisms. The disilane (NN)Si(Hal)-(R)Si(NN)(Hal=Cl or Br) is
      thermally labile and mild thermolysis yields the corresponding monosilane
      (NN)Si(R)(Hal) and silylene 1. Additionally, strong evidence is presented for a
      radical pathway for the reaction of 1 and RHal.

PMID- 16094486
TI  - Neural mechanism of rapid eye movement sleep generation: Cessation of locus
      coeruleus neurons is a necessity.
AB  - Two types of neurons are involved in the regulation of rapid eye movement (REM)
      sleep, the REM-ON and the REM-OFF neurons. As the name suggests, the REM-OFF
      neurons cease firing during REM sleep and they are norepinephrinergic. It has
      been shown that cessation of these neurons is a pre-requisite for the generation
      of REM sleep and GABA shuts them off. Further, if these neurons do not shut off,
      there is increased levels of norepinephrine in the brain and loss of REM sleep.
      The REM sleep deprivation induced increase in norepinephrine is responsible for
      mediating at least REM sleep loss induced increase in Na(+)-K(+) ATPase activity,
      which is likely to be the primary factor for causing REM sleep deprivation
      induced effects.

PMID- 16094487
TI  - Role of the central interleukin-1 in stress responses.
AB  - The molecules of interleukin-1 (IL-1) system are widely distributed in central
      nervous system. As a classical pro-inflammatory factor, central IL-1 has diverse
      biological functions and plays a pivotal role in a number of important
      physiological and pathophysiological processes. During the past few years,
      particular attentions have been directed to the stress mediator actions of
      central IL-1. This paper reviews some recent findings in the studies of central
      IL-1 functions in stress responses, including the effects of stress on central IL
      1, the roles of IL-1 in the initiation of stress responses, the neural
      circuitries and intracellular signal transduction pathways involved in the
      central IL-1 mediated stress responses, as well as the actions of central IL-1 on
      brain high function and behavior under stressful conditions.

PMID- 16094488
TI  - Transcription factor Egr-1 is required for long-term fear memory and anxiety.
AB  - The zinc finger transcription factor Egr-1 is critical for coupling extracellular
      signals to changes in cellular gene expression. In the hippocampus and amygdala,
      two major central regions for memory formation and storage, Egr-1 is up-regulated
      by long-term potentiation (LTP) and learning paradigms. Using Egr-1 knockout
      mice, we showed that Egr-1 was selectively required for late auditory fear memory
      while short term, trace and contextual memory were not affected. Additionally,
      synaptic potentiation induced by theta burst stimulation in the amygdala and
      auditory cortex was significantly reduced or blocked in Egr-1 knockout mice. Our
      study suggests that the transcription factor Egr-1 plays a selective role in late
      auditory fear memory.

PMID- 16094489
TI  - Expression of man, a formin homology domain-containing gene in the mouse limb.
AB  - Formin defines a family of structurally related proteins that have two formin
      homology domains (FH1 and FH2). Various mutations in the formin locus result in
      limb deformity, suggesting that these genes play indispensable roles in the limb
      development. Here we report the isolation of a novel cDNA, man, from the mouse
      limb, which contains two conserved FH1 and FH2 domains. Its expression is
      described and possible functional significance is discussed.

PMID- 16094490
TI  - [Enhanced BK(Ca) single-channel activities in cerebrovascular smooth muscle cells
      of simulated microgravity rats.].
AB  - The aim of the present study was to investigate the changes in single-channel
      currents of large conductance calcium-activated potassium channels (BK(Ca)
      channels) in cerebral vascular smooth muscle cells (VSMCs) of rats after 1-week
      simulated microgravity. Sprague-Dawley rats were subjected to tail-suspension
      (SUS) to simulate cardiovascular deconditioning due to microgravity. Cytosolic
      calcium ([Ca(2+)](i)) was examined by laser-scanning confocal microscopy with
      calcium-sensitive-dye Fluo-3/AM as fluorescent probe. Single-channel currents of
      BK(Ca) channels were measured with cell-attached membrane patches bathed in
      symmetrical high potassium solution. The [Ca(2+)](i)i level was significantly
      higher in cerebrovascular myocytes of SUS than that of control (CON) rats. The
      probability of open (Po) and the mean open time (To) of BK(Ca) channels in
      cerebral VSMCs significantly increased in SUS as compared with CON. However,
      there were no significant differences in the unitary conductance and mean close
      time (Tc) between the two groups. The results obtained suggest that both the
      elevated [Ca(2+)](i) and enhanced single-channel activities of BK(Ca) channels in
      cerebral VSMCs might be among the electrophysiological mechanisms that mediate
      the increased vasoreactivity and hypertrophic change in cerebral arteries during
      adaptation to simulated microgravity in rats.

PMID- 16094491
TI  - Protective and anti-fatigue effects of aspirin against heatstroke in rats.
AB  - The purpose of this study is to determine whether aspirin can reduce interleukin
      1beta(IL-1beta) concentration and exert protective effects against heatstroke.
      The heatstroke rat model was established through exposing rat to a high ambient
      temperature (HAT, Ta 41 degrees C, relative humidity 65%) in a simulative HAT
      chamber to induce heatstroke. Three parts were performed in the present
      experiment: (1) To determine the effects of pretreatment with aspirin against
      heatstroke;(2) To prove the effects of specifically reducing inducible nitric
      oxide synthase (iNOS) against rat heatstroke by iNOS selective prohibitor
      aminoguanidine (AG);(3) To determine the effects of aspirin against heatstroke
      and fatigue. In part 1 and 2, Sprague-Dawley rats were randomly assigned to
      control and aspirin groups or AG groups respectively. Mean arterial blood
      pressure (MAP), colonic temperature (T(co)), electrocardiograph (ECG) were
      monitored during heat exposure (HE) and blood samples were taken 0 and 60 min
      after HE for IL-1betaassay or nitric oxide (NO) assay. In part 3, additional
      control and aspirin groups of conscious rats were put in a barrel with 41 degrees
      C water and kept swimming until drowning over 10 s, and then intervals were
      recorded as survival time. The results from part 1 showed that from 0 to 50 min
      after HE, MAPs of control group and aspirin group were not significantly
      different. About 50-60 min after HE, MAPs of both groups were decreased abruptly
      and MAPs of control group were decreased significantly in comparison with those
      of aspirin group. T(co) of both groups was increased until to 42 degrees C,
      without significant difference. Time of heatstroke onset was not significantly
      different, while survival time was significantly longer in aspirin group than
      that in control group. Plasma IL-1betaconcentrations in both groups were
      significantly increased after HE, and the concentration was significantly higher
      in the control group than that in aspirin group 60 min after HE. In part 3, the
      survival time was significantly longer in aspirin group than that in control
      group. In part 2, MAPs of both groups from 0 to 50 min after HE were not
      significantly different, whereas 55-60 min after HE, MAPs of control group were
      decreased significantly in comparison with those of AG group;T(co) of both groups
      was increased after HE until to 42 degrees C, but without significant difference.
      The time of the heatstroke onset and survival time of AG group were significantly
      longer than that of control group;the plasma NO concentrations of two groups were
      significantly higher 60 min after HE than those 0 min after HE, and the plasma NO
      concentration of control group was significantly higher than that of AG group 60
      min after HE. In conclusion, IL-1betamay contribute to heatstroke through
      inducing iNOS, which attenuates the tone of peripheral blood vessel, and
      pretreatment with aspirin can provide preventive effects against heatstroke and
      reinforce the heat and fatigue endurance, which may be associated with inhibition
      of systemic IL-1betalevels and local iNOS levels.

PMID- 16094492
TI  - [Angiotensin-converting enzyme inhibitors potentiate subthreshold preconditioning
      through NO and mitoK(ATP) channel.].
AB  - The aim of the present study was to determine whether angiotensin-converting
      enzyme inhibitors (ACEI) could contribute to the protective effects of
      preconditioning, and to explore its underlying mechanism. The Langendorff model
      of isolated rat heart was used. Cardiac contractility and lactate dehydrogenase
      (LDH) in the coronary effluent were measured, and infarct area of hearts after 30
      min of ischemia followed by 120 min of reperfusion was analyzed. We found that:
      (1) The subthreshold preconditioning (2 min of ischemia and 10 min of
      reperfusion), captopril (an ACEI with sulfhydryl groups) or perindoprilate (an
      ACEI without sulfhydryl groups) alone did not protect the hearts from being
      injured by 30 min of ischemia and 120 min of reperfusion. (2) However, the
      combination of captopril or perindoprilate with subthreshold preconditioning
      could decrease left ventricular end-diastolic pressure (LVEDP), increase left
      ventricular developed pressure (LVDP) and coronary flow compared with the
      subthreshold preconditioned group. The combination treatments also inhibited the
      release of LDH from ischemia/reperfusion hearts, and reduced the infarct area in
      ischemic heart after 2 h of reperfusion (P<0.05). (3) By using NOS inhibitor L
      NAME (100 mumol/L) before combined administration of ACEI with subthreshold
      preconditioning, the protection effect triggered by the combination treatment was
      significantly reduced. Pretreatment of the hearts with mitochondrial ATP
      sensitive potassium (mitoK(ATP)) channel inhibitor 5-HD (100 mumol/L) also
      abolished the protection effect (P<0.05). (4) Subthreshold preconditioning,
      captopril or perindoprilate alone could enhance the NO content in coronary
      effluent (P<0.05), but the combination of captopril or perindoprilate with
      subthreshold preconditioning could further augment the NO content compared with
      the subthreshold preconditioned group (P<0.05). The results indicate that ACEIs
      with or without sulfhydryl groups may potentiate the subthreshold preconditioning
      to trigger cardiac protection effect against the ischemia/reperfusion injury.
      This protection effect in the heart is possibly mediated by the generation of NO
      and the activation of mitoK(ATP) channel.

PMID- 16094493
TI  - [Influence of acetazolamide given intraperitoneally on the latency to hyperbaric
      oxygen-induced convulsion of rats.].
AB  - The purpose of the present study was to explore the relation between the
      modulation of cerebral blood flow and the latency of hyperbaric oxygen-induced
      convulsion. There were two parts in this study. First, the effect of
      acetazolamide or (and) indomethacin on the latency of hyperbaric oxygen-induced
      convulsion was observed. Seventy Sprague-Dawley (SD) rats were randomly divided
      into 7 groups: the acetazolamide 200, 20, 10, 7.5, 5, 2.5 mg/kg body weight and
      normal saline (NS) group. Forty rats were divided into 5 groups: indomethacin 20,
      10, 5, 2.5 mg/kg body weight and NS groups. Another 40 rats were divided into 5
      groups which were administered with indomethacin in the dose of 0 mg/kg (NS), 0
      mg/kg (NS), 5, 10 and 20 mg/kg body weight. Thirty min later the first group was
      given NS, and all the other four groups were given acetazolamide with a dose of
      7.5 mg/kg body weight. The animals were given acetazolamide or (and) indomethacin
      intraperitoneally, and 20 min later they were exposed to the pressure of 6 ATA
      (absolute atmosphere) of pure oxygen. The time from exposure to the onset of
      seizure (clonic-tonic convulsion) was recorded for each animal according to
      behavioral observation. Second, the change of maleic dialdehyde (MDA) was
      measured after acetazolamide and (or) indomethacin treatment. Seventy-two SD rats
      were randomly divided into 9 groups: Control, 6 and 16 min respectively with NS,
      acetazolamide, indomethacin, and both acetazolamide and indomethacin group. The
      dose of acetazolamide was 7.5 mg/kg body weight and the dose of indomethacin was
      20 mg/kg body weight. After injection of drugs, the animals were subjected to the
      pressure of 6 ATA of pure oxygen in respect to its time course group. Then the
      rats were decapitated and the cerebral cortex was dissected and homogenized. The
      content of MDA was determined. We found that (1) when the dose of acetazolamide
      is higher than 7.5 mg/kg, it shortened the latency to hyperbaric oxygen-induced
      convulsion significantly (P<0.05, P<0.01). There was no significant difference in
      the latency between every to hyperbaric oxygen-induced convulsion significantly
      (P<0.05, P<0.01). There was no significant difference in the latency between
      every two groups of rats treated with different doses of indomethacin. But when
      the rats were administered acetazolamide of 7.5 mg/kg body weight after being
      pretreated with indomethacin of 20 mg/kg body weight, the outbreak of convulsion
      was put off remarkably (P<0.05). (2) In comparison with the control, the content
      of MDA in the group treated with acetazolamide increased significantly (P<0.01),
      but when the rats were treated with both acetazolamide and indomethacin, the
      content of MDA was reduced significantly both in 6 and 16 min exposure time
      projects (P<0.05, P<0.01). These results suggest that acetazolamide which dilates
      the brain arterioles can obviously shorten the latency of hyperbaric oxygen
      induced convulsion and aggravate the oxidation of the brain. Indomethacin can
      resist acetazolamideos effect on the latency and oxidation level when the animals
      were exposed to the hyperbaric oxygen. The activity of carbonic anhydrase
      correlates closely with the oxidation injury.

PMID- 16094494
TI  - Role of glycogen synthase kinase 3 in squamous differentiation of pig airway
      epithelial cells: A primary study.
AB  - To investigate if glycogen synthase kinase 3 (GSK3) is involved in squamous
      differentiation of airway (tracheobronchial) epithelial cells, primary pig airway
      epithelial cells were treated with lithium chloride, a highly selective inhibitor
      of GSK3. Change in morphology of cells was monitored under microscopy, and
      expression of beta-catenin, phosphorylated GSK3 and involucrin, a squamous
      differentiation marker, were dectected by Western blotting, while expression of
      mRNA of another squamous differentiation marker, small proline-rich protein, was
      detected by RT-PCR. Further, luciferase reporter assay was used to assess the
      activation of beta-catenin/Tcf signaling. The results demonstrated that lithium
      was able to induce a squamous morphology of the cells, and to enhance the
      expression of involucrin and small proline-rich protein mRNA. Moreover, lithium
      increased inhibitory phosphorylation of GSK3, augmented nuclear translocation of
      beta-catenin in a dose- and time-dependent manner. Activation of beta-catenin/Tcf
      signaling was observed after the elevation of squamous differentiation markers.
      Taken together, these data suggest that GSK3 is possibly involved in squamous
      differentiation of pig airway epithelial cells.

PMID- 16094495
TI  - [Aromatase inhibitor letrozole induces sex inversion in the protogynous red
      spotted grouper (Epinephelus akaara).].
AB  - The objective of this study was to investigate the effects of the aromatase
      inhibitor (AI) letrozole on gonadal development, serum steroids and aromatase
      activities in 2-year-old female red spotted grouper (Epinephelus akaara) during
      reproductive season. Groupers were divided into two groups, one implanted with
      aromatase inhibitor (AI, 5 mg/kg body weight) and the other elastomer without AI
      into peritoneal cavity once every four weeks for 8 weeks. Spermiation was checked
      through gentle abdominal pressure every 2 weeks. Blood samples were obtained from
      6 fish of each group every 4 weeks for later analysis of sex steroids. After
      blood samples were collected, forebrain, midbrain, hindbrain, and gonads were
      collected and stored at -70 degrees C for later aromatase activity measurement
      and gonadal histological study. Significantly lower gondadosomatic index (GSI)
      was observed in AI-implanted group. Fish implanted with AI once showed complete
      degradation of oocytes and sex inversion with developing testicular tissues in
      the 4th week. AI induced females to develop into functional males with authentic
      males testes similar in structure to those in normal males. Spermiating rate of
      AI-treated males were 14.3%, 35.3%, and 48.4%in the 4th, 6th, and 8th week,
      respectively, while all fish in the control group were still female with
      developing ovaries. Aromatase activities in gonads decreased significantly after
      implantation with aromatase inhibitor, but showed no significant difference
      between control and AI-implanted group. No difference in serum testosterone (T)
      levels was observed in control and AI-treated group, while serum levels of 17beta
      estradiol (E(2)) decreased but 11-ketotestosterone (11-KT) concentration
      increased significantly. The present results suggest that the decrease in serum
      17beta-estradiol (E(2)) and increase in 11-KT levels may be important for sex
      inversion induced by aromatase inhibitor in red spotted grouper.

PMID- 16094496
TI  - [Redistribution of three alpha1-adrenergic receptor subtypes in the stably
      transfected HEK 293A cells upon agonist stimulation.].
AB  - To investigate the subcellular distribution of three alpha(1)-adrenergic receptor
      subtypes and their internalization and trafficking upon agonist stimulation in
      human embryonic kidney (HEK) 293A cell line, saturation radioligand binding
      assay, laser confocal imaging, and Western blot were applied to examine the
      distribution and changes in localization of three alpha(1)-AR subtypes in
      transfected HEK 293A cells prior to and after treatment with phenylephrine. The
      results are as follows: (1) The transfection efficiency was over 90%and was equal
      among three alpha(1)-AR subtypes. alpha(1B ) -AR expression in cell membrane was
      the highest, and alpha(1D ) -AR was the lowest, as determined by (125)I-BE2254
      binding assay, however, K(d)s were not significantly different among the three
      receptor subtypes. (2) Without agonist stimulation, alpha(1A ) -AR was detected
      not only on the cell surface but also in the cytosol, alpha(1B ) -AR was
      predominantly located on the cell surface, whereas alpha(1D ) -AR was mostly
      detected in the cytosol. (3) After 1 h of stimulation with phenylephrine, as
      observed using confocal microscope, less alpha(1A)- and alpha(1B ) -AR were
      detected on the cell surface but more in the cytosol. The change was more
      remarkable in alpha(1B)-AR than that in alpha(1A)-AR, whereas no change of
      distribution was detected in alpha(1D)-AR in response to phenylephrine. However,
      when examined by Western blot, no change in distribution was detected in
      alpha(1A)- and alpha(1D)-AR, only alpha(1B)-AR showed the same change as that
      shown in confocal imaging. It is suggested that the characteristics of
      localization and changes of distribution are different among three alpha(1)-AR
      subtypes in HEK293A cells upon phenylephrine stimulation.

PMID- 16094497
TI  - [Scalable production of embryoid bodies with the rotay cell culture system.].
AB  - Embryonic stem (ES) cells are pluripotent cells capable of extensive
      proliferation while maintaining their potential to differentiate into any cell
      type in the body. ES cells can therefore be considered a renewable source of
      therapeutically useful cells. While ES-derived cells have tremendous potential in
      many experimental and therapeutic applications, the scope of their utility is
      dependent on the availability of relevant cell quantities. Therefore, most of the
      researches are being focused on the differentiation of ES cells. ES cell
      aggregation is important for embryoid body (EB) formation and the subsequent
      generation of ES cell derivatives. EB has been shown to recapitulate aspect of
      early embryogenesis, including the formation of a complex three-dimensional
      architecture wherein cell-cell and cell-matrix interactions are thought to
      support the development of the three embryonic germ layers and their derivatives.
      Standard methods of EB formation include hanging drop and liquid suspension
      culture. Both culture systems maintain a balance between allowing ES cell
      aggregation necessary for EB formation and preventing EB agglomeration for
      efficient cell growth and differentiation. However, they are limited in their
      production capacity. In this paper, we established a new approach for the mass
      production of EBs in a scalable culture system. The rotary cell culture system
      (RCCS, STLV type) was adopted to produce EBs. The vessel was placed on its rotary
      base and the experiment started with a beginning rotation rate of approximately 8
      r/min which has been previously determined empirically as the optimal initial
      speed to yield randomized gravitational vectors while minimizing fluid shear
      stress. To keep the aggregations pfloating in simulated microgravityq, the
      rotation rate was increased as the EBs visibly grew. The EB production efficiency
      was calculated when different cell densities were inoculated. The kinetic change
      of EBs was measured during the time course of EB formation. Compared with the
      traditional method of producing EBs with hanging drop, the multi-potential of the
      resulting EBs in RCCS was analyzed by the capability of cardiomyocyte genesis.
      The results showed that EBs could be produced by RCCS with high efficiency. The
      optimal cell density inoculated in RCCS was 10000 cells/ml, in which EB
      production was about twice higher than that in the suspending culture. Day 4-5
      was the optimal time point for harvesting EBs. To clarify whether the
      differentiated potential of EBs might be affected by the microgravity produced by
      the rotary cell culture system, cardiogenic induction during ES cell
      differentiation was evaluated in our study. It was manifested by appearance of
      spontaneously and rhythmically contracting myocytes. In addition, immuno
      histological and RT-PCR detection showed that the harvested EBs in RCCS exhibited
      the expected cardiac genesis and morphology. So, scalable production of EBs is
      obtained by RCCS. It will provide a useful approach to generate a large quantity
      of ES-derived cells for further research or application.

PMID- 16094498
TI  - [Dynamic changes of found in inflammatory zone 1 protein and mRNA expression in
      the lung with experimental pulmonary fibrosis of the rat.].
AB  - To investigate the role of found in inflammatory zone 1 (FIZZ1) protein in the
      pathogenesis of experimental pulmonary fibrosis, 48 male Sprague-Dawley rats were
      randomly divided into two groups, the pulmonary fibrosis group and the control
      group. Rat pulmonary fibrosis was reproduced by an intratracheal injection of
      bleomycin (5 mg/kg body weight). Normal saline (1 ml/kg body weight) was given
      intratracheally injection in the control group. There were 24 rats in each group,
      and 6 animals were separately killed on the 7th, 14th, 21th and 28th day after
      treated with bleomycin or normal saline. Then the following tests were
      undertaken: (1) HE and Masson staining of lung section;(2) Determination of lung
      tissue hydroxyproline (HYP);(3) Immunohistochemical staining of protein of FIZZ1
      in the lung;(4) In situ hybridization of FIZZ1 mRNA in the lung. The results
      showed: (1) There were full of inflammatory cells in the lung, the interval of
      alveoli enlarged and many alveolar spaces disappeared on the 7th day after
      treated with bleomycin in the fibrosis group. Collagen began to proliferate after
      14 d. The pulmonary fibrosis was stably established on the 28th day, full of
      green fibers in the Masson staining of lung section. (2) The expression of FIZZ1
      protein in the lung increased after 7 d in bleomycin-treated animals (3.013+/
      0.326 vs 0.473+/-0.056, P<0.01 vs control), but was slightly decreased on the
      14th day (2.124+/-0.197) and expensively decreased on the 21st day (1.760+/
      0.105) and the 28th day (0.691+/-0.081). (3) The expression of FIZZ1 mRNA in the
      lung also increased after 7 d by treated with bleomycin (3.795+/-0.338 vs 0.678+/
      0.087, P<0.01 vs control), but decreased on the 14th day (1.276+/-0.104) and
      further decreased on the 28th day (0.896+/-0.084). The expression of FIZZ1
      protein and mRNA in fibrosis group was higher than that in the control group
      (P<0.05 or P<0.01). The results suggest that FIZZ1 protein and FIZZ1 mRNA are
      dynamically changed in the lung with experimental pulmonary fibrosis, which may
      contribute to the pathogenesis of pulmonary fibrosis.

PMID- 16094499
TI  - [Expression of p57 and homeobox A10 during decidualization of endometrial stromal
      cell in vitro.].
AB  - In order to elucidate the function of homeobox A10 gene (HOXA10) and p57 during
      decidualization our present study was designed to observe the change of HOXA10
      and p57 expression and subcellular localization of HOXA10 in the process of
      endometrial stromal cell (ESC) differentiation in vitro. Decidualization was
      induced by 0.5 mmol/L 8-Bromo-cAMP (8-Br-cAMP) together with 1x10(-6) mol/L
      medroxyprogesterone acetate (MPA). Expression of p57 and HOXA10 was detected by
      RT-PCR and Western blot after 1-day, 2-day, and 4-day treatment (D1, D2, D4).
      ESCs cultured in 2%FBS for 1 and 4 d were used as control (C1, C4). The location
      of HOXA10 was detected by indirect immunofluorescence and HOXA10-GFP
      transfection. The results are as follows: (1) The expression of HOXA10 decreased
      progressively during the course of decidualization, and showed significant
      difference compared to control group C4 after 2-day treatment (D2). (2) On the
      contrary, the expression of p57 increased progressively and also showed
      significant difference compared to the control group C4 after 2-day treatment
      (D2). (3) There was no significant change of HOXA10 and p57 expression after
      culturing ESCs in 2%FBS for 4 d (C1, C4). (4) HOXA10 located in the nucleus
      throughout the course. Cytoplasm and nucleus shuttle was not detected in the
      experiment. Our results suggest that the down-regulation of HOXA10 may contribute
      to the increase of p57 and that the up-regulation of p57 likely plays an
      important role in ESC differentiation. Progesterone receptor (PR) pathway may
      participate in promoting ESCs to exit cell cycle and enter differentiation.

PMID- 16094500
TI  - [Wnt signalling pathway regulates the growth and several phenotypes of Rat-1
      cells.].
AB  - The Wnt signaling pathway is thought to be functionally conserved in vertebrates
      and invertebrates and plays an important role during the embryonic and
      postembryonic development. Recent studies indicated that this pathway may be also
      involved in the controlled proliferation and migration of some kinds of
      fibroblasts during the wound healing process. To verify this assumption in vitro,
      we chose Rat-1, a kind of rat fibroblasts to investigate the regulation of Wnt
      signaling pathway to the growth and changes of several phenotypes of this kind of
      cells. Full length Wnt-3a cDNA was inserted in pcDNA 3.1 vector to construct the
      Wnt-3a mammalian expression vector, which was stably transfected into Rat-1
      cells, and then to establish a cell model in which Wnt signaling pathway was
      constantly activated. When Wnt signaling pathway was activated constantly, Rat-1
      cells exhibited morphological changes: grew more densely as a monolayer, adopted
      an elongated and refractile appearance, forming cord-like bundles lined up in a
      uniform direction. The results of MTT assay and FCM analysis indicated that more
      Rat-1/Wnt-3a cells entered into G(2) phase and the proliferation rate of the Rat
      1/ Wnt-3a cells increased significantly compared to the non-transfected cells.
      Though the migration of Rat-1/Wnt-3a cells increased slightly by the method of
      Transwell migration assay, there was no statistic significance compared to the
      non-transfected cells. The result of in vitro scrape wound healing assay showed
      that for Rat-1/Wnt-3a cells the time course of wound healing decreased
      significantly. It is therefore concluded that the activation of Wnt signaling
      pathway can regulate some of the phenotypes of Rat-1 cells, facilitate cell
      proliferation and promote the scrape wound healing in vitro.

PMID- 16094501
TI  - Phenomenon of non-associative learning in Hering-Breuer reflex simulated by
      electrical vagal stimulation in rabbits.
AB  - The purpose of this study was to explore learning and memory in the Hering-Breuer
      (HB) reflex simulated by a 60-second-long electrical stimulation of vagus nerve.
      The responses of phrenic nerve discharge to electrical stimulation (10-100 Hz, 20
      60 muA, pulse duration 0.3 ms, for 60 s) of the vagus nerve were observed in
      rabbits. The results showed that 60-second-long stimulation of vagus nerve
      produced classic HB reflex, which is composed of two components - lung inflation
      reflex that is the inhibition of inspiration, and lung deflation reflex that is
      the facilitation of inspiration. (1) High frequency stimulation (>/=40 Hz, 60 s)
      of the central end of vagus nerve induced shortening of the inspiratory phase and
      lengthening of expiratory duration. The inhibitory effect on phrenic discharge
      was released gradually during sustained vagal stimulation, indicating the
      habituation of the inhibition. At the cessation of stimulation, the phrenic
      discharge showed transient post-stimulus rebound. Low frequency stimulation (<40
      Hz, 60 s) of the central end of vagus nerve caused an increase in respiratory
      frequency (f) and shortening of expiratory duration. The excitatory effect on
      phrenic discharge was also released gradually during the vagal stimulation. The
      phrenic discharge returned to control level gradually after the removal of the
      vagal stimulus, indicating short-term potentiation (STP). (2) The habituation of
      HB reflex was inversely dependent on stimulus intensity and frequency. With an
      increase in the stimulus frequency or intensity, the degree of the habituation
      decreased. On the other hand, with the decrease of stimulation intensity and
      frequency, the degree of the habituation increased. These data indicate a
      phenomenon of non-associative learning in HB reflex simulated by vagal
      stimulation. Neural synaptic plasticity and accommodation may exist in the reflex
      control of respiration in rabbits.

PMID- 16094502
TI  - [Effect of soy isoflavones on cAMP/PKA pathway in breast cancer cells of the
      rat.].
AB  - Soy isoflavones have been reported to be natural chemopreventive in several types
      of human cancer. Daidzein and genistein are two main components of soy
      isoflavones. In our previous study, they were shown to be anti-proliferative and
      induce cell cycle arrest at S phase of SHZ-88 rat breast cancer cells. We
      hypothesized that soy isoflavones might exert its anticancer effect by activating
      cAMP/PKA pathway. The present study was designed to analyze the effect of soy
      isoflavones on the cAMP/PKA pathway in SHZ-88 cells. Daidzein and genistein were
      dissolved in DMSO. Cells were treated with 50 mug/ml daidzein and 15 mug/ml
      genistein, respectively, and with only equal DMSO in the culture medium as
      control. The cellular cAMP content was tested by radioimmunoassay (RIA). The
      activity of adenylate cyclase (AC), phosphodiesterase (PDE) and PKA were measured
      by RIA and (gamma-(32)P) ATP incorporation. Reverse transcript-polymerase chain
      reaction (RT-PCR) was used to analyze the expression of cAMP response element
      binding protein (CREB) mRNA of the cells. The results showed that the
      concentration of cAMP in the cells treated with 50 mug/ml daidzein and 15 mug/ml
      genistein was significantly increased by 9.5%and 11.0%, respectively, 5 min later
      (P<0.05), then increased by 31.0%and 40.3%, respectively, 10 min later (P<0.01),
      compared with that of the control group cells. The activity of AC was not
      affected during the course of experiment, but that of PDE was decreased to
      71.8%and 71.6%, respectively, in the control group 5 min later (P<0.05). The PKA
      activity was increased to 125.8%and 122.3%, respectively, in the control group 20
      min after the cells were treated with daidzein and genistein (P<0.05), and kept
      at high level till 40 min after treatment. CREB mRNA of the cells treated with
      daidzein and genistein was increased by 31.6%and 51.1%, respectively, 3 h later
      (P<0.05), then began to decrease 6 h after treatment. The current study suggests
      that soy isoflavones activate the cAMP/PKA pathway in SHZ-88 rat breast cancer
      cells by inhibiting the activity of phosphodiesterase.

PMID- 16094503
TI  - Resveratrol inhibits the electrical activity of subfornical organ neurons in rat.
AB  - The effects of resveratrol on the discharges of neurons in rat subfornical organ
      (SFO) slices were examined by using extracellular recording technique. The
      results are as follows: (1) In response to the application of resveratrol (1, 5,
      10 mumol/L, n=65) into the superfusate for 2 min, the spontaneous discharge rate
      of 60/65 (92.3%) neurons was significantly decreased in a dose-dependent
      manner;(2) Application of L-glutamate (0.3 mmol/L) into the superfusate led to a
      marked increase in discharge rate of all 12 (100%) neurons in an epileptiform
      pattern. The increased discharges of 10/12 (83.3%) neurons were suppressed by
      application of resveratrol (5 mumol/L);(3) In 8 neurons, the selective L-type
      calcium channel agonist, Bay K8644 (0.1 mumol/L), induced a significant increase
      in discharge rate of all 8 (100%) neurons. The increased discharges of all 8
      (100%) neurons were suppressed by resveratrol (5 mumol/L);(4) In 14 neurons,
      nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME)
      50 mumol/L significantly increased the discharge rate of 11/14 (78.6%) neurons.
      Resveratrol (5 ?mol/L) applied into the superfusate reduced the increased
      discharges of 9/11 (81.8%) neurons;(5) In 12 neurons, the large-conductance
      Ca(2+)-activated K(+) channel blocker tetraethylammonium chloride (TEA) 1 mmol/L
      significantly increased the discharge rate of 10/12 (83.3%) neurons. Resveratrol
      (5 mumol/L) inhibited the increased discharges of 9/10 (90%) neurons. These
      results suggest that resveratrol inhibits the electrical activity of SFO neurons.
      This effect may be related to its properties of blockade of L-type voltage-gated
      calcium channel and nitric oxide (NO) promoting, and probably has no association
      with large-conductance Ca(2+)-activated K(+) channel.

PMID- 16094504
TI  - Effects of neuroglobin gene transfer in vivo on hearing response properties of
      neurons in the inferior colliculus in mice after administration of sodium
      salicylate.
AB  - The effects of neuroglobin (NGB) gene transfer in vivo mediated by GeneJamer on
      the hearing response properties of the inferior colliculus (IC) neurons in mice
      after administration of sodium salicylate were studied. Forty-eight Kunming mice
      were divided into 4 groups (n=12 in each group): Group A1 (negative
      control);Group A2 (positive control);Group B, sodium salicylate (450 mg/kg every
      day) + pEGFP-C1;Group C, sodium salicylate (450 mg/kg every day) + pEGFP-NGB. The
      GeneJamer and pEGFP-NGB were mixed and injected into IC neurons in mice. The
      expression of NGB mRNA and protein of IC neurons in mice was detected by using RT
      PCR and Western blot methods. The intensity-rate functions, intensity-latency
      functions and frequency-turning curves in IC neurons were recorded by
      extracellular electrophysiological recording techniques and the effects of pEGFP
      NGB transfer following injection of sodium salicylate on them were studied. It
      was found that: (1) The GeneJamer-mediated pEGFP-NGB could be effectively
      transferred into the IC brain tissues in mice and NGB could be expressed
      intensively. (2) The intensity-rate functions of IC neurons were raised after
      administration of sodium salicylate. The non-monotonic styles of intensity-rate
      functions in groups A1, A2 and C were accounted for 74.6%, 72.2 %, 59.3 %,
      respectively, and the function in group B for 47%. There were significant
      differences between group B and groups A1, A2 or C (P<0.01, P<0.01, P<0.05). (3)
      The intensity-latency functions in IC neurons were reduced after administration
      of sodium salicylate. The non-monotonic styles of intensity-latency functions in
      groups A1, A2 and C were accounted for 3.2 %, 5.1 %and 21 %, respectively, and
      that in group B for 45.5 %. There were significant differences between group B
      and groups A1, A2 or C (P<0.01, P<0.01, P<0.05, respectively). (4) The frequency
      turning curves in groups A1 and A2 were sharpened. In 72 acoustic neurons
      recorded in the group B, the frequency-turning curves from 53 neurons were
      broadened while those of the rest were sharpened. In group C the frequency
      turning curves recorded from 12 of 67 acoustic neurons were broadened while those
      of the remaining were sharpened. These results suggest that in vivo transfer of
      NGB gene is highly expressed in IC neurons in mice. In vivo transfer of NGB gene
      reverses the change of intensity-rate functions, intensity-latency functions and
      the code styles after administration of sodium salicylate in IC neurons in mice.

PMID- 16094505
TI  - Assessment of PACS display systems.
AB  - This work describes our experience in reviewing the performance criteria for
      display systems and how we have implemented a practical approach to the
      assessment of the workstation environment in a large tertiary care hospital. The
      acceptance criteria contained in the draft report of Topic Group 18 of the
      American Association of Physicists in Medicine (AAPM) were used as a basis for
      assessment of primary and secondary displays. A telescopic photometer was used to
      measure the maximum luminance and the contrast ratio of the image for the
      displays used in our radiology department and in the operating and emergency
      rooms using the standard Society of Motion Picture and Television Engineers
      (SMPTE) pattern, in ambient light and with light decreased as much as possible.
      About half of the displays met the AAPM criteria for minimum luminance and
      contrast ratio in low light. None of the systems met the contrast ratio criteria
      in ambient light. The challenges in improving the performance and calibrating
      displays are discussed.

PMID- 16094506
TI  - The ability of history and a negative cough stress test to detect occult stress
      incontinence in patients undergoing surgical repair of advanced pelvic organ
      prolapse.
AB  - To determine if a negative preoperative reduction cough stress test is a viable
      method of detecting occult stress incontinence or urge incontinence in women
      undergoing surgical repair of advanced pelvic organ prolapse. A retrospective
      chart review was done on all patients who denied any urinary complaints and had
      repair of advanced pelvic organ prolapse, grade two or greater, without the
      addition of an anti-incontinence procedure. Additionally patients had a simple
      office filling study done at the time of initial examination that failed to show
      the sign of stress incontinence or detrusor instability. Any urinary dysfunction
      that developed postoperatively was noted. A total of 53 patients met the
      inclusion criteria. Of these patients, one patient (1.9%) developed genuine
      stress incontinence, and one patient complained of urgency (1.9%). Patients
      without urinary complaints and a negative office filling study, who were present
      for surgical correction of advanced pelvic organ prolapse, have a low incidence
      of developing occult stress incontinence. Further work-up would not be cost
      effective.

PMID- 16094507
TI  - Does the MONARC transobturator suburethral sling cause post-operative voiding
      dysfunction? A prospective study.
AB  - The aim of this study was to compare pre-operative and post-operative voiding
      parameters following insertion of the MONARC transobturator tape (TOT), for
      treating women with urodynamic stress incontinence. This prospective
      observational study was conducted at a tertiary referral urogynaecology unit, in
      North Queensland, involving 83 women who were prospectively assessed pre
      operatively and at 6-8 weeks following the procedure. Information collected
      included patient demographics, concomitant surgery, pre-operative and post
      operative symptomatology (using validated questionnaires), and pre-operative and
      post-operative urodynamic parameters. Parameters used to assess voiding function
      included symptoms of voiding difficulty (incomplete emptying and irritative
      symptoms) as well as objective parameters including maximum flow rate (Qmax),
      adjusted maximum flow rate (Qmaxadj) using the Liverpool nomogram (LN), maximal
      urethral pressure, and post-void residual (PVR). Pre-operative average Qmax was
      23.7 ml/s compared to 21.1 ml/s post-operatively (p=0.064). When the Qmax was
      adjusted for voided volume using the LN, Qmaxadj was seen to decrease
      significantly from 26 ml/s to 18 ml/s (p<0.05). Women with PVR>50 ml did not
      differ significantly pre-operatively and post-operatively, 5/83(6%) vs 7/83
      (8.4%) (p=0.75). The number of women with a flow rate <10th centile on LN was 22
      (26.5%) pre-operatively vs 29 (34.9%) post-operatively (p=0.21). One (1.2%) post
      operatively had voiding dysfunction diagnosed by an abnormal voiding pattern
      (p=0.728), which was not statistically significant. Objective voiding dysfunction
      as determined by adjusted flow rates <10th centile LN and >50 ml PVR was seen in
      four women (4.8%). Adjusted free flow rates are significantly reduced following
      insertion of the MONARC TOT, as are some symptoms related to voiding dysfunction.
      Despite this, satisfaction rates remain high with observed voiding dysfunction or
      objective measures of voiding dysfunction showing no statistical change in the
      short term. Long-term follow-up is planned at 1 year.

PMID- 16094508
TI  - Microvascular decompression for primary hemifacial spasm. Importance of
      intraoperative neurophysiological monitoring.
AB  - There is considerable evidence that primary Hemi-Facial Spasm (HFS) is in almost
      all cases related to a vascular compression of the facial nerve at its Root Exit
      Zone (REZ) from brainstem, and that Micro-Vascular Decompression (MVD)
      constitutes its curative treatment. Clinical as well as electrophysiological
      features plead for mechanisms of the disease in structural lesions at the neural
      fibers (putatively: focal demyelination at origin of ephapses) and functional
      changes in the nuclear cells (hyperactivity of the facial nucleus). Lateral
      Spread Responses (LSRs) elicited by stimulation of the facial nerve branches
      testify of these electrophysiological perturbations. Monitoring LSRs during
      surgery is feasible; however the practical value of their intraoperative
      disappearance as control-test of an effective decompression remains
      controversial.MVD allows cure of the disease in most cases. Because the VIIIth
      nerve is at risk during surgery, intraoperative monitoring of Brainstem Auditory
      Evoked Potentials (BEAPs) is of value to reduce occurrence of hearing loss.
      Increase in latency of Peak V and decrease in amplitude of Peak I are warning
      signals of an excessive stretching of the the cochlear nerve and impairment of
      the cochlear vascular supply, respectively.

PMID- 16094509
TI  - Artificial liver support: future aspects.
AB  - Liver transplantation and blood purification therapy, including plasmapheresis,
      hemodiafiltration, and bioartificial liver support, are available to treat
      patients with severe liver failure. The two mainstream systems developed for
      bioartificial liver support are extracorporeal whole-liver perfusion (ECLP) and
      the bioreactor system (BIS). We developed a method of plasma cross-perfusion, in
      which plasma is exchanged between the blood circuit of the patient and that of a
      hepatic function unit, that is, whole liver or a bioreactor through which
      immunologically free whole human blood is perfused. From the aspects of efficacy
      and safety, the best system of bioartificial liver support for clinical use is
      considered to be ECLP in cross plasma perfusion. However, a social objection
      about zoonosis has consistently been raised, with controversy surrounding the use
      of xenogeneic organs for human treatment, and this might be a final obstacle to
      the development of system efficacy. The combination therapy of hemodiafiltration
      with the administration of human serum albumin and anticoagulant factors can
      minimize the economic and medical resource costs through the development of
      transgenic livestock that secrete human pharmaceuticals systemically. It is
      possible that this therapy will become the most practical treatment for patients
      with severe hepatic failure.

PMID- 16094510
TI  - Drug targeting with nano-sized carrier systems.
AB  - This paper discusses the present status of, and future perspectives on, drug
      targeting through the bloodstream by describing the drug targeting concept, its
      methodologies, types of drug carriers, and recent clinical examples. This
      explanation and discussion is made from the viewpoint of possible correlations
      with studies on artificial organs, implants, and biomaterials. Two targeting
      methodologies (active and passive targeting), two targeting strategies (the magic
      bullet and the enhanced permeability and retention effect), and five types of
      drug carriers are explained. In addition, the clinical status of the five carrier
      systems is discussed.

PMID- 16094511
TI  - Use of a soft reservoir bag in a fully heparin-coated closed-loop cardiopulmonary
      bypass system for distal aortic perfusion during aortic surgery.
AB  - A fully heparin-coated closed-loop cardiopulmonary bypass system has recently
      been introduced into clinical practice. Without a venous reservoir, however, it
      does not allow control of the preload to the heart. We connected a soft reservoir
      bag in parallel with a centrifugal pump to enable preload control and clinically
      evaluated this modified system for distal aortic perfusion during aortic surgery.
      We have used the modified system in 17 patients since November 2002. For venous
      drainage, we use long narrow cannulae (21 +/- 2 French). We administered 1 mg/kg
      heparin without cardiotomy suction and 2 mg/kg heparin with suction. We compared
      the clinical results with those in 13 patients who underwent distal aortic
      perfusion with an open cardiopulmonary bypass circuit between January 2002 and
      February 2004. We also analyzed factors affecting the coagulation system in these
      30 patients using multiple regression analysis. With the modified system, venous
      drainage was adequate despite the use of smaller cannulae, and heparin reduction
      was not associated with thrombotic complication or elevated D-D dimer levels.
      Abrupt rises in proximal aortic pressure on aortic cross-clamping could be
      avoided by allowing blood to drain into the soft reservoir bag. Clinical results
      were not different from those with an open system. In the multiple regression
      analysis, the peak activated clotting time tended to correlate with postoperative
      platelet counts. This system is effective in controlling the preload to the heart
      and allows the safe reduction of heparin dosage. It therefore seems useful for
      distal aortic perfusion during aortic surgery.

PMID- 16094512
TI  - Venous drainage method for cardiopulmonary bypass in single-access minimally
      invasive cardiac surgery: siphon and vacuum-assisted drainage.
AB  - Vacuum-assisted venous drainage (VAVD) can facilitate venous drainage in single
      access minimally invasive cardiac surgery (SAMICS). We retrospectively examined
      the use of VAVD in SAMICS in our hospital for this report. VAVD has been
      performed according to a VAVD protocol since 2000. Data from the 110 patients who
      underwent SAMICS in our institute from January 2000 to June 2002 were reviewed
      retrospectively. The total negative pressure was maintained at no greater than 
      90 mmHg. Indications for use of VAVD (protocol) were: insufficient venous return
      by siphon drainage alone, persistent elevation of the central venous pressure
      (CVP), and, insufficient venous drainage in the operative field. Of 110 patients,
      97 (88.2%) underwent VAVD. The body surface area was significantly smaller in the
      group that did not require VAVD (the non-VAVD group) than in the group that did
      (VAVD group) (VAVD group versus non-VAVD group: 1.586 +/- 0.175 versus 1.408 +/-
      0.153 m(2), P < 0.001). Other factors such as cardiopulmonary bypass time, aortic
      cross-clamp time, postoperative maximum lactate dehydrogenase, postoperative
      maximum creatinine, postoperative maximum blood urea nitrogen were similar in the
      two groups. VAVD is necessary in SAMICS except for small patients. A VAVD total
      negative pressure of -90 mmHg did not hinder operative procedures or cause
      clinical problems.

PMID- 16094513
TI  - Early clinical results of St. Jude Medical Symmetry aortic connector.
AB  - An automated anastomosis device named St. Jude Medical symmetry aortic connector
      has been used worldwide for off-pump coronary artery bypass grafting. However,
      early graft obstruction was recently reported, and its predictors should be
      clarified. From April 2002 to March 2004, 38 patients in our institution
      underwent off-pump coronary artery bypass grafting using the St. Jude Medical
      Symmetry aortic connector for saphenous vein graft (SVG) procedures; measurement
      of intraoperative graft flow and postoperative coronary angiography was
      performed. Early SVG events occurred in 9 (24%) patients: 8 occlusion cases and 1
      case of stenosis. Predictors of early SVG events were assessed from a comparative
      study. Univariate logistic regression identified hyperlipidemia as the only
      significant predictor of early SVG events (P = 0.02, odds ratio 7.78). Lower SVG
      flow rate and poor ejection fraction did not show statistical significance (P =
      0.09, odds ratio 1.09 and P = 0.09, odds ratio 0.96). The SVG event rate was much
      higher for the left circumflex branch compared with other locations (31% vs. 9%,
      P = 0.03) and decreased with increasing aortic connector size (small, 32%;
      median, 14%; large, 0%). Multivariate analysis did not identify a predictor of
      SVG events. The aortic connector is associated with a high incidence of early SVG
      events. Patients should be cautiously selected and the procedure should not be
      used for left anterior descending coronary artery or culprit lesions.

PMID- 16094514
TI  - QRS width does not reflect ventricular dyssynchrony in patients with heart
      failure.
AB  - The purpose of this study was to evaluate QRS width as an indication for cardiac
      resynchronization therapy. This study group consisted of 64 heart failure
      patients (51 men, age average 60.5 +/- 15.5 years) with a left ventricular
      ejection fraction (LVEF) of less than 35%. Patients were divided into two groups
      according to their QRS width; the wide QRS group (QRS width greater than or equal
      to 120 ms, 31 patients) and the narrow QRS group (QRS width less than 120 ms, 33
      patients). The ventricular dyssynchrony (VD), i.e., the inter- and
      intraventricular dyssynchrony, of the two groups was compared. The correlation
      between QRS width and VD was evaluated in all patients. There were no significant
      differences between the wide and the narrow QRS groups concerning
      interventricular dyssynchrony [28.4 +/- 26.1 ms vs. 25.3 +/- 18.2 ms, not
      significant (NS)] or intraventricular dyssynchrony (99.0 +/- 43.8 ms vs. 109.0 +/
      56.6 ms, NS). Nor were there any differences in the LVEF (26.6 +/- 6.6% vs. 28.2
      +/- 5.1%, NS), brain natriuretic peptide (BNP) (567.0 +/- 319.0 pg/ml vs. 390.0
      +/- 375.8 pg/ml, NS), and New York Heart Association (NYHA) class (2.4 +/- 0.8
      vs. 2.0 +/- 1.0, NS). QRS width did not correlate with interventricular (r =
      0.026, NS) or intraventricular dyssynchrony (r = 0.052, NS). There were no
      differences in VD between the two groups based on differences in QRS width. There
      was also no correlation between QRS width and VD. It is suggested that QRS width
      is not an absolute indication for cardiac resynchronization therapy.

PMID- 16094515
TI  - Enhancement of liver-specific functions of primary rat hepatocytes co-cultured
      with bone marrow cells on tissue culture-treated polystyrene surfaces.
AB  - Primary rat hepatocytes were co-cultured with bone marrow cells (BMCs) in a
      tissue culture-treated culture well (TCW) or a collagen-coated culture well
      (CCW). Although a medium containing serum was used, the co-cultured cells formed
      spheroids on the TCW within 2 days, and ammonia metabolism and albumin secretion
      activities were well maintained for 3 weeks. The co-cultured cells formed a
      monolayer on the CCW within 2 days, and liver functions were maintained for 3
      weeks. The ammonia metabolism activities and albumin secretion activities of co
      cultured cells on the CCWs were slightly inferior to those on the TCWs. This co
      culture system of hepatocytes and BMCs is an appropriate culture system for the
      expression and maintenance of liver-specific functions in vitro, and is expected
      to be applicable to bioartificial liver systems, regenerative medicine, and liver
      function simulators.

PMID- 16094516
TI  - Differentiation from embryonic stem cells to vascular wall cells under in vitro
      pulsatile flow loading.
AB  - This study evaluated the possibility of differentiation from embryonic stem (ES)
      cells to vascular wall cells by physical (mechanical) stress loading in vitro. A
      cell mixture containing Flk1-positive cells (ca. 30%) derived from murine ES
      cells was added to a compliant microporous tube made of segmented polyurethane.
      The compliance of the tube was close to that of the human artery [the stiffness
      parameter (beta) = 57.2 (n = 5, SD < 5%)]. The luminal surface of the tube was
      fully covered with the cells by preincubation for two days in the presence of
      vascular endothelial growth factor (VEGF). After 2 days of additional incubation
      without VEGF under static conditions, layering of the grown cells, mostly smooth
      muscle actin (SMA)-positive cells, was observed only on the luminal surface of
      the tube. The cells were flat, polygonal, and randomly oriented. On the other
      hand, after a 2-day incubation under a weak pulsatile flow simulating the human
      venous systems [wall shear stress (WSS) from -0.98 to 2.2 dyn/cm(2);
      circumferential strain (CS) 4.6-9.6 x 10(4) dyn/cm(2)] without VEGF, cells in the
      superficial layer were regularly oriented in the direction of the pulsatile flow.
      The oriented cells exhibited endothelial-like appearance, indicating that they
      were platelet endothelial cell adhesion molecule 1 (PECAM1)-positive. In
      addition, the cells growing into the interstices in the deeper layer showed
      smooth muscle-like appearance, indicating that they were SMA-positive.
      Differentiation to two different cell types and segregation of incorporated ES
      cells may be simultaneously encouraged by the combination of WSS and CS. It is
      expected that the monobloc building of hierarchically structured hybrid vascular
      prostheses composed of several vascular wall cell types is possible by physically
      synchronized differentiation of ES cells.

PMID- 16094517
TI  - Development of sutureless vascular connecting system for easy implantation of
      small-caliber artificial grafts.
AB  - A novel sutureless vascular connecting system, an assembly with a delivery rod,
      an introducing sheath, and a connecting device, was developed for easy
      implantation of small-caliber vascular grafts less than 2 mm in internal
      diameter. A microporous stainless tube (length 2 mm, external diameter 1.6 mm,
      wall thickness 65 microm, pore diameter 400 microm, pore-to-pore distance 500
      microm) was designed to serve as a connecting device. The feasibility of the
      system was tested using two types of preliminary animal experiments. One animal
      model consisted of graft implantation into the rat abdominal aorta (1.5 mm in
      diameter). The connecting device was inserted into the proximal and distal ends
      of the aorta through the introducing sheath by pushing the delivery rod with the
      connecting device placed over it. Subsequently, the aortic segments were inserted
      into both ends of model grafts made of segmented polyurethane (1.8 mm in internal
      diameter) and were fixed with banding silk threads from the exterior. The
      procedure was completed within 20 min without requiring specialized microsurgery
      techniques. Blood leakage and obstruction did not occur. The second model
      consisted of an end-to-end anastomosis between rabbit common carotid arteries (2
      mm in diameter), which was performed within several minutes of blood flow
      interruption. Scanning electron microscopy demonstrated that the luminal surface
      of the device was fully covered with endothelial cells (ECs) after 1 week as a
      result of transluminal ingrowth of native ECs through the micropores in the
      device. This endothelialization may prevent early thrombus-induced occlusion.
      This simple and "easy-to-learn" technique will promote the development of small
      caliber arterial grafts, and furthermore, it may have potential for clinical
      application.

PMID- 16094518
TI  - The effect of peritoneal rest in combination therapy of peritoneal dialysis and
      hemodialysis: using the cultured human peritoneal mesothelial cell model.
AB  - The effects of peritoneal rest for 24 h during peritoneal dialysis and
      hemodialysis combination therapy were investigated using cultured human
      peritoneal mesothelial cell (HPMC) models. Cell activity was investigated by 3
      [4,5-dimethylthiazol-2-yl]-2, 5-diphenylterazolium bromide (MTT) assay after
      exposing HPMCs to peritoneal dialysis fluids (PDFs) with different pH levels. The
      following PDFs (50 microl/well) were used for exposure durations of 30 or 240
      min: acidic heat-sterilized PDFs (L-H PDF, pH 5.5) and neutral heat-sterilized
      PDFs (N-H PDF, pH 6.7). Control wells were exposed to M-199 Hanks medium
      containing 20% fetal bovine serum (FBS) for 30 or 240 min. Supernatants were then
      aspirated from each well and M-199 culture medium containing 20% FBS (50 microl)
      was added to each well to rest HPMCs for 24 h before investigation of MTT
      activity. The activity of HPMCs exposed to L-H PDF for 240 min decreased to
      approximately 20% and 15% when compared with controls (glucose concentrations of
      1.36% and 3.86%, respectively; P < 0.01 versus control, Tukey-Kramer test), and
      to approximately 60% and 40% after exposure to N-H PDF for 240 min (glucose:
      1.36% and 3.86%; P < 0.01). The activity of HPMCs exposed to L-H PDF for 240 min
      followed by rest was approximately 20% and 4% when compared with controls
      (glucose: 1.36% and 3.86%; P < 0.01) and was 93% and 96% when compared with
      controls after exposure to N-H PDF for 240 min followed by rest (glucose: 1.36%
      and 3.86%). These findings suggest that rest for 24 h after exposure to N-H PDF
      improves the activity of HPMCs.

PMID- 16094521
TI  - Multiple malign gastrointestinal polyps and rectal carcinoma in a young patient
      with Peutz-Jeghers syndrome.

PMID- 16094519
TI  - Prospective, double-blind, randomized trial of equimolar mixture of nitrous
      oxide/oxygen to prevent pain induced by insertion of venous access ports in
      cancer patients.
AB  - BACKGROUND: To assess the efficacy of equimolar mixture of nitrous oxide/oxygen
      (EMNO) to prevent pain induced by venous access ports (VAPs) implantation in
      cancer patients. PATIENTS AND METHODS: In a randomized, double-blind study on an
      adult population not knowing the effects of EMNO, cancer patients were randomly
      assigned to breath via a facial mask, EMNO or a placebo mixture comprising 50%
      oxygen and 50% nitrogen. The primary end-point was the patients' assessment of
      the severity of pain evaluated using a visual analog scale (VAS, 0 to 100) and
      the proportion of patients suffering pain in each group. The secondary criteria
      were side effects, tolerability of EMNO, and the level of satisfaction of both
      the patients and the medical team. RESULTS: Eighty-three adults (42 in the EMNO
      group and 41 in the placebo group) were included. VAPs were implanted in the
      jugular vein in 95% of patients. In the placebo group, 78% of the patients
      declared that they found VAP implantation painful vs. 34% in the EMNO group
      (p=0.001). The severity of the pain was reduced by 50% in the EMNO group in
      comparison with placebo (p=0.0125). Although the median time to perform
      implantation was strictly identical in both groups (20 min), the estimated
      duration of surgery seemed longer to patients in the control group. Patient and
      investigator satisfaction indexes were >90% in both groups. CONCLUSION: EMNO
      provides an effective solution for the prevention of pain during placement of
      VAPs.

PMID- 16094522
TI  - [Indicators for early prediction of outcome in sepsis].
AB  - Sepsis is still a major cause of postoperative morbidity and mortality. Numerous
      biochemical indicators have been evaluated regarding their potential in
      predicting prognosis in sepsis. Generally, one must differentiate between
      indicators: those for preoperative detection of patients at risk for lethal
      sepsis and those for early prediction of lethal outcome of septic complications.
      The first include the analysis of mononuclear phagocyte interleukin (IL)-12
      synthesizing capability. Reduced IL-12 levels were associated with higher
      lethality. Cytokine-associated gene polymorphisms such as the loss of monocyte
      HLA-DR expression and homozygotism for the tumor necrosis factor B2 allele have a
      place in preoperative risk evaluation, as they were associated with worse
      prognosis in sepsis. Among the most important biochemical indicators for early
      prediction of lethal outcome in sepsis are decreased L-selectin and elevated IL
      18, IL-6, and PCT plasma concentrations. Increased nuclear factor kappaB activity
      in mononuclear phagocytes and elevated calcitonin gene-related protein plasma
      concentrations were associated with unfavourable prognosis.

PMID- 16094523
TI  - Cytokine expression profile in human pancreatic carcinoma cells and in surgical
      specimens: implications for survival.
AB  - Cytokine shedding by tumor cells into the local microenvironment modulates host
      immune response, tumor growth, and metastasis. The study aimed to verify the
      hypothesis that the immunological microenvironment of pancreatic carcinoma exists
      in a prevalently immunosuppressive state, influencing survival. We analyzed
      expression profiles of pro-inflammatory (IL-1beta, IL-2, IL-6, IL-8, IL-12 p40,
      IL-18 and IFN-gamma) and anti-inflammatory (IL-10, IL-11, IL-13 and TGF-beta
      isoforms) cytokines. The study was performed both in vitro, in five pancreatic
      carcinoma cell lines (real time RT-PCR), and in specimens from 65 patients,
      comparing tumoral versus non-tumoral pancreatic tissues (real time RT-PCR and
      immunohistochemistry). Furthermore, cytokines were measured in supernatants and
      sera (from patients and controls) by ELISA. All cell lines expressed IL-8, IL-18,
      TGF-beta1, TGF-beta2 and TGF-beta3, but not IFN-gamma and IL-2 transcripts.
      Expression of IL-1beta, IL-6, IL-10, IL-11, IL-13 and IL-12 mRNA was variable.
      All the above cytokines were detected as soluble proteins in supernatants, except
      IL-13. Tumor tissues overexpressed IL-1beta, IL-6, IL-8, IL-10, IL-11, IL-12 p40,
      IL-18, IFN-gamma, TGF-beta1, TGF-beta2 and TGF-beta3 at the mRNA level and IL
      1beta, IL-18, TGF-beta2 and TGF-beta3 also at the protein level. Conversely, non
      tumor tissues had stronger RNA and protein expression of IL-13. Survival was
      significantly longer in patients with high IL-1beta and IL-11 and moderate IL-12
      expression. Serum IL-8, IL-10, IL-12, IL-18, TGF-beta1 and TGF-beta2 were higher
      in patients than in controls, as opposed to IL-1beta and IL-13. Patients with low
      circulating levels of IL-6, IL-18 and TGF-beta2 survived longer. Pancreatic
      cancer is characterized by peculiar cytokine expression patterns, associated with
      different survival probabilities.

PMID- 16094525
TI  - Etomidate and intensive care physicians.

PMID- 16094526
TI  - Histological study of embryo-like structures initiated from hypocotyl segments of
      flax (Linum usitatissimum L.).
AB  - Cultivation of flax hypocotyl segments on MS medium supplemented with auxin (2,4
      D, NAA) and combination of auxin (NAA) and cytokinin (BAP, zeatin) resulted in
      production of callus on the cut ends of segments and prolonged cultivation in
      globular structures resembling early stages of somatic embryos. Embryo-like
      structures protruded on the surface directly from the subepidermal layers of
      hypocotyl segments. Despite these globular structures closely resembling somatic
      embryos, histological observations did not reveal their embryogenic character
      organogenesis was the predominant developmental morphogenic pathway. Based on our
      experiments, as well as on critical revision of existing reports on flax somatic
      embryogenesis, we conclude, that there has not yet been convincing histological
      proof of somatic embyogenesis from flax hypocotyl segments.

PMID- 16094527
TI  - Ajmalicine production in methyl jasmonate-induced Catharanthus roseus cell
      cultures depends on Ca2+ level.
AB  - Cytosolic Ca(2+) and jasmonate mediate signals that induce defense responses in
      plants. In this study, the interaction between Ca(2+) and methyl jasmonate (MJ)
      in modulating defense responses was investigated by monitoring ajmalicine
      production in Catharanthus roseus suspension cultures. C. roseus suspensions were
      treated with nine combinations of CaCl(2) (3, 23, and 43 mM) and MJ (0, 10, and
      100 microM) on day 6 of growth. Increased Ca(2+) influx through the addition of
      extracellular CaCl(2) suppressed ajmalicine production in MJ-induced cultures.
      The highest ajmalicine production (4.75 mg/l) was observed when cells were
      treated with a low level of calcium (3 mM) combined with a high level of MJ (100
      microM). In the presence of 3 mM CaCl(2) in the medium, the addition of Ca(2+)
      chelator EGTA (1, 2.5, and 5 mM) or Ca(2+) channel blocker verapamil (1, 10, and
      50 muM) to MJ-induced (100 microM) cultures on day 6 also inhibited ajmalicine
      production at higher levels of the Ca(2+) inhibitors. Hence, ajmalicine
      production in MJ-induced C. roseus cultures depended on the intracellular Ca(2+)
      concentration and a low extracellular Ca(2+) concentration (3 mM) enhanced MJ
      induced ajmalicine production.

PMID- 16094528
TI  - In vitro induction of tetraploid plants from diploid Zizyphus jujuba Mill. cv.
      Zhanhua.
AB  - Tetraploid plants of Zizyphus jujuba Mill. cv. Zhanhua were obtained with in
      vitro colchicine treatment. Shoot tips from in vitro-grown plants were treated
      with five different concentrations of colchicine (0.01, 0.03, 0.05, 0.1, 0.3%) in
      liquid MS medium (Murashige and Skoog 1962), and shaken (100 rpm) at 25 degrees C
      in darkness for 24, 48, 72 or 96 h, respectively. Tetraploids were obtained at a
      frequency of over 3% by using 0.05% colchicine (48 h, 72 h) and 0.1% colchicine
      (24 h, 48 h) treatment as determined by flow cytometry. Cytological and
      morphological evidence confirmed the results of flow cytometric analysis. The
      chromosome number of diploid plants was 24 and that of tetraploid plants was 48.
      The stomata sizes of tetraploid plants were significantly larger than those of
      diploid plants, while the frequency of stomata were reduced significantly.
      Similarly, the chloroplast number of guard cells of tetraploid plants increased
      significantly. The selected tetraploid plants were grafted onto mature trees of
      Z. jujuba Mill. cv. Zhanhua in the field, resulted in thicker stems, rounder and
      succulent leaves, larger flowers and a delay in florescence time (3-4 days later)
      than diploid plants.

PMID- 16094529
TI  - The epidemiology of left ventricular hypertrophy in type 2 diabetes mellitus.
AB  - AIMS/HYPOTHESIS: Patients with type 2 diabetes mellitus are at greater
      cardiovascular risk than the general population. Although it is widely
      acknowledged that diabetes is a risk factor for coronary artery disease, the
      increased prevalence of potentially lethal left ventricular abnormalities in this
      population is less well appreciated. METHODS: We carried out an echocardiographic
      study of 500 subjects with type 2 diabetes mellitus to assess the prevalence of
      left ventricular hypertrophy (LVH) and left ventricular systolic dysfunction
      (LVSD). We also assessed whether abnormalities in diastolic filling parameters
      were present. RESULTS: Of the 371 patients in whom left ventricular mass could be
      successfully assessed, 264 had LVH (71%). Left ventricular systolic dysfunction
      was much less common, being present in 16/385 patients (4.2%). Long axis
      contraction was abnormal in 29/429 patients (6.8%). Diastolic filling
      abnormalities were present in 178/435 (41%) of patients who could be classified
      using the selected criteria. CONCLUSIONS: We conclude that left ventricular
      abnormalities are common in type 2 diabetic patients. As medical therapy is
      available for both LVH and LVSD and has been demonstrated to reduce
      cardiovascular death, these left ventricular abnormalities could be ideal targets
      for screening, followed by selective therapeutic intervention.

PMID- 16094530
TI  - Expression and function of receptors for insulin-like growth factor-I and insulin
      in human coronary artery smooth muscle cells.
AB  - AIMS/HYPOTHESIS: Hyperinsulinaemia and insulin resistance, as well as low IGF-I,
      have been implicated in the pathogenesis of cardiovascular disease. Little is
      known about direct effects of IGF-I and insulin on human coronary artery smooth
      muscle cells (HCASMCs). Our aim was to characterise the expression and function
      of IGF-I receptor (IGF-IR) and insulin receptor (IR) in HCASMCs. MATERIALS AND
      METHODS: Cultured HCASMCs were used. mRNA expression was measured by quantitative
      real-time RT-PCR analysis. Receptor proteins, phosphorylation of beta-subunits
      and the presence of hybrid IR/IGF-IR were analysed by immunoprecipitation and
      western blotting. DNA synthesis and glucose metabolism were assessed using
      [3H]thymidine incorporation and D-[U-14C]glucose accumulation respectively.
      RESULTS: The mRNA expression of IGF-IR was approximately eight-fold higher than
      that of IR in HCASMCs. The presence of IGF-IR and IR could be demonstrated by
      immunoprecipitation and western blot analysis. Phosphorylation of the IGF-IR beta
      subunit was obtained by IGF-I at 10(-10)-10(-8) mol/l and insulin at 10(-8)
      mol/l. Insulin and IGF-I at 10(-10)-10(-9) mol/l phosphorylated the IR beta
      subunit. When immunoprecipitated with monoclonal anti-IR alpha-subunit or IGF-IR
      alpha-subunit antibodies, we found bands in slightly different positions,
      suggesting the presence of hybrid IR/IGF-IR. IGF-I at 10(-9)-10(-8) mol/l
      significantly stimulated [3H]thymidine incorporation and at a concentration of
      10(-9)-10(-7) mol/l also D-[U-14C]glucose accumulation in HCASMCs. Insulin at 10(
      9)-10(-7) mol/l had no effect on DNA synthesis, but increased glucose
      accumulation at 10(-7) mol/l. CONCLUSIONS/INTERPRETATION: Our study provides
      experimental evidence that IGF-IR and possibly hybrid IR/IGF-IR play a role in
      HCASMCs.

PMID- 16094531
TI  - Adverse physicochemical properties of tripalmitin in beta cells lead to
      morphological changes and lipotoxicity in vitro.
AB  - AIMS/HYPOTHESIS: Long-term exposure of beta cells to lipids, particularly
      saturated fatty acids in vitro, results in cellular dysfunction and apoptosis
      (lipotoxicity); this could contribute to obesity-related diabetes. Our aims were
      to relate cell death to intracellular triglyceride concentration, composition and
      localisation following incubation of INS1 cells in saturated and unsaturated NEFA
      in high and low glucose concentrations. MATERIALS AND METHODS: Insulin-producing
      INS1 cells were cultured (24 h; 3 and 20 mmol/l glucose) with palmitic, oleic or
      linoleic acids and the resulting intracellular lipids were analysed by gas
      chromatography and microscopy. Cell death was determined by quantitative
      microscopy and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay, and glucose-stimulated insulin secretion by ELISA. RESULTS: All NEFA (0.5
      mmol/l, 0.5% albumin) inhibited glucose-stimulated (20 mmol/l) insulin secretion.
      Cytotoxicity was evident only with palmitic acid (p<0.05), in which case
      intracellular triglyceride consisted largely of tripalmitin in angular-shaped
      dilated endoplasmic reticulum. Cytotoxicity and morphological disruption were
      reduced by addition of unsaturated NEFA. Triglyceride content (control cells;
      14.5 ng/mug protein) increased up to 10-fold following incubation in NEFA (oleic
      acid 153.2 ng/mug protein; p<0.05) and triglyceride and phospholipid fractions
      were both enriched with the specific fatty acid added to the medium (p<0.05).
      CONCLUSIONS/INTERPRETATION: In INS1 cells, palmitic acid is converted in the
      endoplasmic reticulum to solid tripalmitin (melting point >65 degrees C), which
      could induce endoplasmic reticulum stress proteins and signal apoptosis; lipid
      induced apoptosis would therefore be a consequence of the physicochemical
      properties of these triglycerides. Since cellular triglycerides composed of
      single species of fatty acid are not likely to occur in vivo, destruction of beta
      cells by saturated fatty acids could be predominantly an in vitro scenario.

PMID- 16094532
TI  - Receptor for platelet-activating factor (PAF) is not detectable by flow cytometry
      on the surface of myeloid leukemic cells.
AB  - Flow cytometry was applied to test for platelet-activating-factor receptor (PAF
      R) presence on the membranes of acute myeloid leukemia (AML) cells. We have used
      six human AML cell lines and freshly taken density gradient separated blasts from
      the bone marrow of ten AML patients covering the majority of French-American
      British (FAB) subtypes. Additionally, we have used one histiocytic lymphoma cell
      line and mature human granulocytes/monocytes as controls. Our results indicate
      lack of membrane PAF-R on AML of all FAB subtypes tested. This was particularly
      true for the more mature and differentiated subtypes M4 and M5, including
      monocytic cell elements, and the promyelocytic M3 AML. In contrast, membrane PAF
      R could be easily detected in a histiocytic lymphoma cell line and mature
      granulocytes/monocytes from peripheral blood used as positive controls. In
      conclusion, this observation precludes the use of membrane PAF-R as an
      immunophenotypic marker for AML classification or detection of minimal residual
      disease.

PMID- 16094533
TI  - Determination of phenols in waters using micro-pumped multicommutation and
      spectrophotometric detection: an automated alternative to the standard procedure.
AB  - An automated and greener spectrophotometric procedure has been developed for the
      determination of phenol in water at 700 nm. The method uses the reaction between
      phenol, sodium nitroprusside, and hydroxylamine hydrochloride in a buffered
      medium at pH 12.3. The flow manifold comprises four solenoid micro-pumps employed
      for sample and reagent introduction into the reaction coil and to transport the
      colored product formed to the detector. The linear dynamic range was 50-3,500 ng
      mL(-1) (R = 0.99997; n = 6) and the method provided a limit of detection (3sigma)
      of 13 ng mL(-1). The sampling throughput was estimated to be 65 measurements per
      hour and the coefficient of variation was 0.5% (n = 10) for a 1.0 microg mL(-1)
      phenol concentration. Recoveries of 92-105% were obtained for phenol
      determination in spiked water samples at concentration levels from 50 to 5,000 ng
      mL(-1). The use of multicommutation reduced the reagent consumption 25-fold, the
      sample consumption 225-fold, and the waste generation 30-fold compared with the
      batch procedure. The proposed method is an environmentally friendly alternative
      to the official 4-aminoantipyrine method since it avoids the use of chloroform.

PMID- 16094534
TI  - Structure prediction of a multi-domain EF-hand Ca2+ binding protein by PROPAINOR.
AB  - PROPAINOR is a new algorithm developed for ab initio prediction of the 3D
      structures of proteins using knowledge-based nonparametric multivariate
      statistical methods. This algorithm is found to be most efficient in terms of
      computational simplicity and prediction accuracy for single-domain proteins as
      compared to other ab initio methods. In this paper, we have used the algorithm
      for the atomic structure prediction of a multi-domain (two-domain) calcium
      binding protein, whose solution structure has been deposited in the PDB recently
      (PDB ID: 1JFK). We have studied the sensitivity of the predicted structure to NMR
      distance restraints with their incorporation as an additional input. Further, we
      have compared the predicted structures in both these cases with the NMR derived
      solution structure reported earlier. We have also validated the refined structure
      for proper stereochemistry and favorable packing environment with good results
      and elucidated the role of the central linker.

PMID- 16094535
TI  - Molecular modeling of phosphorylation sites in proteins using a database of local
      structure segments.
AB  - A new bioinformatics tool for molecular modeling of the local structure around
      phosphorylation sites in proteins has been developed. Our method is based on a
      library of short sequence and structure motifs. The basic structural elements to
      be predicted are local structure segments (LSSs). This enables us to avoid the
      problem of non-exact local description of structures, caused by either diversity
      in the structural context, or uncertainties in prediction methods. We have
      developed a library of LSSs and a profile--profile-matching algorithm that
      predicts local structures of proteins from their sequence information. Our
      fragment library prediction method is publicly available on a server (FRAGlib),
      at http://ffas.ljcrf.edu/Servers/frag.html . The algorithm has been applied
      successfully to the characterization of local structure around phosphorylation
      sites in proteins. Our computational predictions of sequence and structure
      preferences around phosphorylated residues have been confirmed by phosphorylation
      experiments for PKA and PKC kinases. The quality of predictions has been
      evaluated with several independent statistical tests. We have observed a
      significant improvement in the accuracy of predictions by incorporating
      structural information into the description of the neighborhood of the
      phosphorylated site. Our results strongly suggest that sequence information ought
      to be supplemented with additional structural context information (predicted with
      our segment similarity method) for more successful predictions of phosphorylation
      sites in proteins.

PMID- 16094536
TI  - [Venous ulcer on lateral edge of foot].

PMID- 16094537
TI  - CYP2C9*3 allelic variant is associated with metabolism of irbesartan in Chinese
      population.
AB  - OBJECTIVE: There is considerable variability in the individual pharmaceutical
      dosages required to achieve optimal therapeutic effects, which may be due to
      environmental or genetic factors. The objective of this study was to test the
      presence of the CYP2C9*3 allelic variant in the Chinese population and to
      investigate the association of this variant with both metabolism and therapeutic
      efficacy of irbesartan on essential hypertension. METHODS: In this study, we
      enrolled 711 subjects from Taihu County and 376 subjects from Dongzhi County in
      Anhui Province, China. All subjects received a single oral dose of 150 mg
      irbesartan daily for 28 days. The plasma concentration of irbesartan at 24 h
      after dosing on the 27th day and at 6 h after dosing on the 28th day was detected
      using fluorescence-high-performance liquid chromatography. CYP2C9 genotypes were
      determined using polymerase chain reaction-restriction fragment length
      polymorphism. RESULTS: No CYP2C9*2 allele was found in 235 Chinese samples and
      was removed from further study. The mean frequency of the CYP2C9*3 allele was
      3.65%, while no CYP2C9*3/*3 genotype was detected. Multiple linear regression
      analyses revealed that the CYP2C9*3 allele carriers had significantly higher
      irbesartan concentrations in plasma at 6 h (Taihu: P < 0.0001; Dongzhi: P = 0.03)
      and 24 h (Taihu: P < 0.0001; Dongzhi: P = 0.00013) after dosing. No significant
      association was found between the CYP2C9*3 allelic variant and the therapeutic
      effect of irbesartan on essential hypertension. CONCLUSION: Our study suggests
      that the CYP2C9*3 plays an important role in the metabolism of irbesartan and/or
      is in linkage disequilibrium with another potential CYP2C9 allele, both of which
      possibly modify the pharmacokinetics of irbesartan.

PMID- 16094538
TI  - Retinacular band excision improves outcome in treatment of plica syndrome.
AB  - Mild symptoms usually continue after excision of the medial patellar plica. We
      noticed that the palpable tender cord, located on the anteromedial aspect of the
      knee in patients with plica syndrome, did not disappear completely after excision
      of the synovial fold. Beneath all plicae, a retinacular band was visible, and
      only after excisions of this band did the cord become impalpable. We conducted a
      study to determine the role of these medial retinacular bands in the
      symptomatology of the disorder. Twenty-four knees of 22 patients diagnosed with
      medial patellar plica syndrome were divided into two groups. In the first group,
      arthroscopic excision of the synovial plica was performed. In the second group,
      retinacular bands beneath the plica were additionally excised. When Lysholm
      scores were compared, we found that the second group showed significantly greater
      improvement. We believe that the retinacular bands play a role in the
      symptomatology and the pathophysiology of plica syndrome and that excision
      improves the outcome.

PMID- 16094539
TI  - Delayed surgical treatment for neglected or mal-reduced talar fractures.
AB  - From 1993 to 2002, we treated nine patients for neglected or mal-reduced talar
      fractures. Average patient age was 39 (20-64) years and average follow-up 53
      months. The time interval between injury and index operation ranged from 4 weeks
      to 4 years. Surgical procedures included open reduction with or without bone
      grafting in six cases, open reduction combined with ankle fusion in one case,
      talar neck osteotomy in one case, and talar neck osteotomy combined with subtalar
      fusion in one case. All cases had solid bone union. One patient developed
      avascular necrosis of the talus needing subsequent ankle arthrodesis. In six
      patients, adjacent hindfoot arthrosis occurred. The overall AOFAS ankle-hindfoot
      score was in average 77.4. We conclude that in neglected and mal-reduced talar
      fractures, surgical treatment can lead to a favourable outcome if the hindfoot
      joints are not arthritic.

PMID- 16094540
TI  - Isolated acetabular revision after total hip arthroplasty: results at 5-9 years
      of follow-up.
AB  - The purpose of the study was to determine whether isolated revision of the
      acetabular component can be successfully performed without disturbing the femoral
      stem and to determine the fate of the unrevised femoral stem following revision.
      Fifty-seven hips in 55 patients underwent isolated acetabular revision without
      removal of the femoral component. Thirty-three hips with minimal acetabular
      deficiency required no bone grafting; the remaining 24 hips were treated by
      morselized or structural allograft in addition to a new acetabular component.
      Twenty-two of these 24 hips demonstrated incorporation of the bone graft. A mean
      follow-up of 5.8 (5-9) years, all femoral and acetabular components were judged
      to be stable and well fixed.

PMID- 16094541
TI  - Sarcomatous change in the Pagetoid tibiae.
AB  - We reviewed 13 cases of tibial Paget's sarcoma constituting 14% of all registered
      Paget's sarcoma cases of the Scottish Bone Tumour Registry between January 1947
      and June 2004. Eleven patients were male, and in ten patients the tumour involved
      the upper half of the tibia. In all cases, the main presenting feature was
      progressively worsening pain followed by a mass in six, a pathological fracture
      in five and tibial bowing in four. In nine patients, a lytic lesion was seen
      radiologically. Histologically, there were three osteosarcomas and ten malignant
      fibrous histiocytomas. Limb ablation was carried out in 11 patients, of whom nine
      had trans-femoral amputation. Six patients received adjuvant radiotherapy and/or
      chemotherapy. Post-operative complications included stump revision in two cases,
      non-union of a pathological fracture of the tibial tuberosity and a stress
      fracture. The median survival was 17 months.

PMID- 16094542
TI  - A follow-up study of patients with spinal cord injury in Sierra Leone.
AB  - Over an 18-month period, 24 patients were admitted with spinal cord injuries in a
      non-governmental organization hospital in one of the world's poorest countries,
      Sierra Leone. Seven patients died while in hospital. Follow-up data was available
      for 13 of the 17 survivors an average of 17.4 (10-28) months after discharge.
      Five patients were still alive.

PMID- 16094543
TI  - Genetic basis of human testicular germ cell cancer: insights from the fruitfly
      and mouse.
AB  - The prevalence of tumours of the germ line is increasing in the male population.
      This complex disease has a complex aetiology. We examine the contribution of
      genetic mutations to the development of germ line tumours in this review. In
      particular, we concentrate on fly and mouse experimental systems in order to
      demonstrate that mutations in some conserved genes cause pathologies typical of
      certain human germ cell tumours, whereas other mutations elicit phenotypes that
      are unique to the experimental model. Despite these experimental systems being
      imperfect, we show that they are useful models of human testicular germ cell
      tumourigenesis.

PMID- 16094544
TI  - Role of plasma lipids and lipoproteins in predicting amphotericin B-induced
      nephrotoxicity in pediatric oncology patients.
AB  - PURPOSE: The objective of this study was to determine if total plasma and
      lipoprotein cholesterol (C) and triglyceride (TG) concentrations could predict
      the degree of nephrotoxicity caused by the antifungal agent amphotericin B
      (AmpB); and to use the average amount of potassium supplementation received daily
      as a indicator of nephrotoxicity in pediatric oncology patients. PATIENTS AND
      METHODS: Plasma samples from 18 patients (ages < 17 years) who were receiving
      AmpB due to suspected or confirmed fungal infection at British Columbia
      Children's Hospital were analyzed for lipid concentrations. The high density
      lipoprotein (HDL) fractions were separated by precipitation; total (TOT) plasma
      and fraction C and TG concentrations were measured by enzymatic colorimetric
      assays; and low density lipoprotein (LDL) C levels were determined by
      Friedewald's formula. Changes in serum creatinine levels from baseline and
      amounts of potassium supplementation were used as indicators of nephrotoxicity;
      both were obtained from patients' medical charts. Pearson correlation
      coefficients (r) were determined and considered significant if P < 0.05. RESULTS:
      The total cumulative AmpB dose, adjusted for weight, does not seem to predict
      AmpB-induced nephrotoxicity. Positive but relatively weak correlations were found
      between total potassium supplementation and LDL C (r = 0.489, P < 0.02); and TOT
      C (r = 0.551, P < 0.01). In addition, a positive but relatively weak correlation
      between the average amount of potassium supplementation per day above baseline
      and HDL C (r = 0.407; P < 0.02) was observed. CONCLUSION: Differences in total
      plasma and LDL cholesterol concentrations may be used as predictors of AmpB
      induced nephrotoxicity in pediatric oncology patients.

PMID- 16094546
TI  - Multifocal osseous involvement as the sole manifestation of Rosai-Dorfman
      disease.
AB  - Rosai-Dorfman disease may involve extranodal sites exclusively. Osseous
      involvement as the sole manifestation of disease is uncommon. The present report
      describes a 60-year-old woman presenting with lytic lesions in the lower end of
      femur and mid-fibula on one side and unaccompanied by disease elsewhere.

PMID- 16094548
TI  - Transmission of hepatitis B in Hamburg, Germany, 1998-2002: a prospective,
      population-based study.
AB  - To study the pattern of transmission of HBV in a large urban community, an in
      depth prospective study was performed in Hamburg between 1 January 1998 and 31
      December 2002. In total, 524 patients were classified as hepatitis B cases
      according to the case definition of the Robert Koch Institute, comprising 197
      foreign-born and 327 German-born persons. The principal risk factor was
      parenteral drug use, with 17.7% (n=93/524) of all documented cases of hepatitis
      B, followed by immigration as refugees (13.9%; n=73). Of all 524 cases, 72
      (13.7%) were associated with heterosexual (n=41) or homosexual (n=31)
      transmission. Household contacts of HBV carriers or of patients with acute
      infectious disease contributed to 9.0% of the cases (n=47). Medical procedures
      were most probably the source in 7.4% (n=39), although only 3.2% (n=17) of all
      patients were health-care workers. In multivariate analysis of household
      contacts, male-male sexual activity was found to be the greatest risk factor for
      acquiring an acute HBV infection, followed by asylum-seeking status and the
      number of contacts. The incidence was 3.5-fold higher among foreign-born persons
      (16.1 per 100,000) than among German-born individuals (4.5 per 100,000)
      suggesting that a targeted intervention in this population group is a public
      health need. The current national policy of vaccination in defined age groups
      should be extended to the immunization of all children of foreign-born parents as
      well as the screening and immunisation of susceptible foreign-born adults.

PMID- 16094545
TI  - Molecular biology of insect olfaction: recent progress and conceptual models.
AB  - Insects have an enormous impact on global public health as disease vectors and as
      agricultural enablers as well as pests and olfaction is an important sensory
      input to their behavior. As such it is of great value to understand the interplay
      of the molecular components of the olfactory system which, in addition to
      fostering a better understanding of insect neurobiology, may ultimately aid in
      devising novel intervention strategies to reduce disease transmission or crop
      damage. Since the first discovery of odorant receptors in vertebrates over a
      decade ago, much of our view on how the insect olfactory system might work has
      been derived from observations made in vertebrates and other invertebrates, such
      as lobsters or nematodes. Together with the advantages of a wide range of genetic
      tools, the identification of the first insect odorant receptors in Drosophila
      melanogaster in 1999 paved the way for rapid progress in unraveling the question
      of how olfactory signal transduction and processing occurs in the fruitfly. This
      review intends to summarize much of this progress and to point out some areas
      where advances can be expected in the near future.

PMID- 16094549
TI  - [The burden on relatives of acute mentally ill within the first four weeks of day
      hospital and inpatient treatment. Results from a randomized controlled trial].
AB  - OBJECTIVE: To assess the burden on relatives as well as their mental well-being
      within the context of a randomized controlled trial on the effectiveness of acute
      psychiatric day hospital treatment as compared to inpatient treatment. METHOD:
      The study was conducted at the Department of Psychiatry and Psychotherapy,
      Dresden University of Technology. A sample of 95 relatives was assessed at
      admission and after four weeks of treatment using the Involvement Evaluation
      Questionnaire (IEQ) and the General Health Questionnaire (GHQ-28), the period to
      be rated being the last four weeks prior to assessment. RESULTS: Relatives
      reported a mean level of burden, which for both settings decreased during the
      first four weeks of treatment. With respect to this period, burden on relatives
      of day hospital patients did not differ from that on relatives of inpatients. The
      relatives' mental well-being was markedly impaired, and only that of the
      inpatients' relatives did slightly improve during treatment. CONCLUSIONS:
      Treating acute mentally ill as day hospital patients does not result in greater
      burden on relatives compared to treating them as inpatients. Independently from
      treatment setting, relatives of psychiatric patients should be actively
      approached and offered information, coping strategies, and help. Further research
      should include qualitative methods.

PMID- 16094551
TI  - [For and against: a crisis of community psychiatry? For].

PMID- 16094550
TI  - [Early rehabilitation for chronic mentally ill during inpatient stay--court
      decision strengthens social-psychiatric treatment approach].

PMID- 16094553
TI  - ["What is a bipolar disorder?" Results of a representative survey of the German
      population].
AB  - AIM: To explore to what extent the lay public knows that the term bipolar
      disorder denotes a mental disorder. METHOD: In January 2005, a telephone survey
      was conducted among a random sample of the German population (n = 1006). Out of
      four options given, respondents were asked to select the one they considered to
      be the correct explanation of what is meant by bipolar disorder. RESULTS: Most of
      the respondents (61%) believed that bipolar disorder is just another term for the
      melting of the polar ice caps, only 4.6 % associated it with mental illness.
      DISCUSSION: The question arises as to whether it makes sense to use a diagnosis
      which the lay public associates with everything but a mental illness. Since it is
      impossible to erase the term bipolar disorder from the psychiatric terminology,
      it seems necessary to increasingly propagate this term among the lay public.

PMID- 16094552
TI  - [Between responsibility and delimitation: emotional distress of caregivers].
AB  - OBJECTIVE: The purpose of this article is to provide an overview regarding the
      emotional burden of relatives of the mentally ill. METHODS: The relevant
      literature were identified by means of a computerized MEDLINE research on the
      years 1993 - 2004 and scanning of review articles. A content analysis of
      interviews with 32 caregivers about their emotional burdens was carried out to
      complete and elucidate the review. RESULTS: The emotional burden of caregivers
      are manifold. Following categories can be distinguished: anxiety and sorrows due
      to the lack of information about the illness and treatment, unsureness and
      overcharge with the symptoms of the illness, sorrows about the treatment of the
      patient, helplessness and palsy, loneliness and responsibility on his own,
      feelings of being excluded from the treatment of the patient, anxiety about the
      future, feelings of restrictions of the own autonomy and problems in demarcation,
      hope and disillusionment, grief and feelings of loss, fear of relapse and
      suicide, sense of shame and stigmatization, discouragement, feelings of guilt,
      anger and disappointment, changes in family roles and role-conflictions, problems
      in the sexuality of the partnership and anxiety about an illness of one's own or
      heredity to the children of one's own. CONCLUSIONS: The distinct knowledge of
      caregivers' emotional burdens can help to avoid overcharging the capacity of the
      carers, to decline high expressed-emotion-levels in the families and to reduce
      relapse rates of the patients.

PMID- 16094554
TI  - [Capability to work in vocational rehabilitation of the severe mentally ill:
      initial predictors and change after six months].
AB  - OBJECTIVE: Persons with severe mental illnesses often need additional vocational
      rehabilitation in order to gain or regain an adequate capability to work. The
      objective of this paper is the assessment of work capability and its development
      throughout the rehabilitation process, as well as clarification of its
      correlating variables, and predictors. METHOD: We present data obtained at two
      different points in time (at rehabilitation program intake and at the six month
      mark of being in the program) from a sample of 117 rehabilitants. Capability to
      work was assessed by using the adapted German version of the Work Personality
      Profile (WPP), called the Arbeitsfahigkeitenprofil (AFP). Additionally,
      sociodemographic, intellectual, psychopathological, and subjective quality of
      life measures were examined. RESULTS: The AFP sum score revealed a significant
      change after six months' participation in the rehabilitation program. More
      precisely, for the subscales "capability to learn" and "communication skills", a
      significant increase was obtained, whereas "social adaptation" showed a non
      significant improvement. CONCLUSION: Our results show that the rehabilitants'
      "capability to work" had improved at the six month mark of the rehabilitation
      program. It appears that baseline variables of the AFP subscales at program
      intake were largely related to psychopathology and subjective quality of life
      measures. Sociodemographic parameters, educational level, and attention measures
      were associated with work capability improvement after six months.

PMID- 16094555
TI  - [Mental distress and the use of psychiatric and psychotherapeutic treatments
      services: results of the Study of Health in Pomerania].
AB  - OBJECTIVE: Due to the lack of adequate data on the need of psychiatric and
      psychotherapeutic care in the community, an evidence-based goal directed
      development of treatment systems in socioeconomically poorer regions in former
      Eastern Germany is not feasible. METHOD: A community sample from the Study of
      Health in Pomerania (N = 4310) was investigated with the "Beschwerdenliste" from
      von Zerssen. The met and the unmet need of care were estimated. RESULTS: 3.1 % of
      all subjects were treated at least once by a mental health professional during
      the last 12 months. 12 % of the subjects, currently not in treatment, were
      estimated to be highly distressed by psychopathological symptoms and were
      considered to be potentially in need of mental health care. From this follows a
      treatment rate of 20 %. Subjects with high mental stress consulted their GP's,
      internists, orthopedics and neurologists significantly more often than subjects
      with low mental stress. CONCLUSION: A considerable need of psychiatric and
      psychotherapeutic treatment facilities has to be faced. Besides the improvement
      of psychiatric and psychotherapeutic treatment facilities, psychosocial networks
      should be established in order to provide an integrative and interdisciplinary
      approach to mental problems in the community.

PMID- 16094556
TI  - [Obscene telephone calls--relations to paraphilias, paraphilia related disorders
      and stalking].
AB  - Little is known about the aetiology, course and therapy of obscene telephone
      calls as a paraphilic behaviour. Overlaps to other paraphilias like voyeurism,
      paraphilia related disorders and the concept of stalking are reported in the
      literature. In case reports we describe the paraphilic development and course
      with a focus on the relationship to the victim. We discuss this on the background
      of different concepts regarding risk assessment and therapy.

PMID- 16094557
TI  - Tulathromycin: an overview of a new triamilide antibiotic for livestock
      respiratory disease.
AB  - Tulathromycin is a novel triamilide antimicrobial that has been approved for use
      in the treatment and prevention of bovine respiratory disease and the treatment
      of swine respiratory disease in the European Union and the United States. The
      agent penetrates gram-negative bacteria well, and it exhibits mixed
      bacteriostatic and bactericidal activity. Tulathromycin is formulated as a ready
      to-use, sterile aqueous solution, and the packaged concentration of 100 mg
      tulathromycin/ml allows low-volume dosing. This agent is characterized by rapid
      absorption from the injection site, extensive distribution to tissue, and slow
      elimination, thereby providing high, prolonged drug concentration in the lungs.
      Studies show that a single dose of tulathromycin is effective in treating cattle
      and swine with respiratory disease and in preventing high-risk cattle from
      developing respiratory disease.

PMID- 16094558
TI  - Efficacy of tulathromycin in the treatment of bovine respiratory disease
      associated with induced Mycoplasma bovis infections in young dairy calves.
AB  - The efficacy of tulathromycin in the treatment of bovine respiratory disease
      (BRD) due to Mycoplasma bovis was determined following experimental infection.
      Two highly pathogenic strains of M. bovis (with minimum inhibitory concentration
      values for tulathromycin of 1 and >64 microg/ml) were inoculated into 145 calves.
      Four days after inoculation, calves with clinical BRD were treated subcutaneously
      with saline or tulathromycin (2.5 mg/kg). Compared with saline, BRD-related
      withdrawals, peak rectal temperatures, and lung lesion scores were significantly
      lower for tulathromycin-treated calves (P < .01). Tulathromycin was highly
      effective in the treatment of BRD due to M. bovis in calves regardless of the
      minimum inhibitory concentration of the challenge strain (1 or >64 microg/ml).

PMID- 16094559
TI  - Minimum inhibitory concentrations of tulathromycin against respiratory bacterial
      pathogens isolated from clinical cases in European cattle and swine and
      variability arising from changes in in vitro methodology.
AB  - The in vitro activity of tulathromycin was evaluated against common bovine and
      porcine respiratory pathogens collected from outbreaks of clinical disease across
      eight European countries from 1998 to 2001. Minimum inhibitory concentrations
      (MICs) for one isolate of each bacterial species from each outbreak were
      determined using a broth microdilution technique. The lowest concentrations
      inhibiting the growth of 90% of isolates (MIC90) for tulathromycin were 2
      microg/ml for Mannheimia (Pasteurella) haemolytica, 1 microg/ml for Pasteurella
      multocida (bovine), and 2 microg/ml for Pasteurella multocida (porcine) and
      ranged from 0.5 to 4 microg/ml for Histophilus somni (Haemophilus somnus) and
      from 4 to 16 microg/ml for Actinobacillus pleuropneumoniae. Isolates were
      retested in the presence of serum. The activity of tulathromycin against
      fastidious organisms was affected by culture conditions, and MICs were reduced in
      the presence of serum.

PMID- 16094560
TI  - Efficacy of tulathromycin in the treatment and prevention of natural outbreaks of
      bovine respiratory disease in European cattle.
AB  - The efficacy of tulathromycin in the treatment (phase 1) and prevention (phase 2)
      of bovine respiratory disease (BRD) was evaluated on commercial farms in France,
      Germany, Italy, and Spain. In phase 1, commingled cattle with clinical BRD were
      treated with tulathromycin (n = 128) or florfenicol (n = 125) on day 0. Similar
      percentages of animals showed sustained clinical improvement at day 14
      (tulathromycin 83.3% versus florfenicol 81.0%) and had not relapsed by day 60
      (tulathromycin 63.3% versus florfenicol 58.4%). In phase 2, healthy in-contact
      cattle were treated with tulathromycin (n = 492), tilmicosin (n = 494), or saline
      (n = 265) on day 0. Significantly more (P = .0001) tulathromycin-treated cattle
      remained healthy to day 14 (92.4%) than tilmicosin-treated (83.7%) or saline
      treated (63.7%) cattle, and this was maintained through day 60 (tulathromycin
      85.4% versus tilmicosin 75.1% and saline 56.2%). Tulathromycin was highly
      effective in the treatment and prevention of BRD.

PMID- 16094561
TI  - Clinical effectiveness of tulathromycin, a novel triamilide antimicrobial, for
      the control of respiratory disease in cattle at high risk for developing bovine
      respiratory disease.
AB  - The efficacy of tulathromycin in decreasing the incidence of morbidity and
      mortality due to bovine respiratory disease (BRD) in 1,239 high-risk cattle was
      investigated at four US feedlots. Calves not exhibiting clinical signs of BRD
      received one of three treatments administered subcutaneously in the neck:
      physiologic saline at 0.02 ml/kg, tulathromycin at 2.5 mg/kg, or tilmicosin at 10
      mg/kg. Each treatment group consisted of 413 calves. Calves with clinical signs
      of BRD and rectal temperatures of 104 degrees F or higher on days 1 through 14
      were considered treatment failures (BRD morbidity). Nasopharyngeal swabs from
      saline-treated morbidities were submitted for isolation and identification of BRD
      organisms. Respiratory disease morbidity was highest in calves treated with
      saline and significantly (P < or = .0001) lower in calves administered
      tulathromycin or tilmicosin. Morbidity from BRD was significantly (P < or =
      .0001) higher in calves treated with tilmicosin than in calves treated with
      tulathromycin. Under conditions of this study, tulathromycin, given to calves at
      high risk of developing BRD, was significantly more effective in reducing BRD
      morbidity when compared to both saline- and tilmicosin-treated calves.

PMID- 16094562
TI  - Therapeutic efficacy of tulathromycin, a novel triamilide antimicrobial, against
      bovine respiratory disease in feeder calves.
AB  - Efficacy and field safety of tulathromycin administered as a single-dose
      treatment to crossbreed beef calves with undifferentiated bovine respiratory
      disease (BRD) were evaluated in a multicenter field study conducted at four US
      feedlots. Two hundred castrated male calves were enrolled at each study site. The
      treatment groups were physiologic saline (n = 160) given SC at 0.02 ml/kg,
      tulathromycin (n = 320) given SC at 2.5 mg/kg, and tilmicosin (n = 320) given SC
      at 10 mg/kg. Nasopharyngeal swabs for bacterial culture were obtained before
      treatment. The cure rate for calves treated with tulathromycin (78%) and
      tilmicosin (65%) was significantly (P < or = .0001) higher than that of calves
      treated with saline (23.8%). The cure rate of calves treated with tulathromycin
      (78.4%) was significantly (P = .0007) higher than that of calves treated with
      tilmicosin (64.9%). No adverse events related to tulathromycin were reported.
      Under the conditions of this study, tulathromycin administered as a single-dose
      treatment was efficacious in the treatment of undifferentiated BRD.

PMID- 16094563
TI  - Efficacy of tulathromycin compared with tilmicosin and florfenicol for the
      control of respiratory disease in cattle at high risk of developing bovine
      respiratory disease.
AB  - Three studies conducted at feedlots in Colorado, Idaho, and Texas examined the
      comparative efficacy of tulathromycin injectable solution for the treatment of
      cattle at high risk of developing undifferentiated bovine respiratory disease
      (BRD). Each study randomly allocated 250 calves to receive tulathromycin at 2.5
      mg/kg and 250 calves to receive either tilmicosin at 10 mg/kg (Colorado site) or
      florfenicol at 40 mg/kg (Idaho and Texas sites) on arrival at the feedlot. Calves
      were housed by treatment group in pens with 50 calves/pen. Beginning 3 days after
      antimicrobial treatment, cattle were observed for signs of BRD daily until
      harvest. In all three studies, the treatment success rates at 28 days after
      treatment and at harvest were significantly higher (P < or = .013) for cattle
      treated with tulathromycin than for cattle treated with either tilmicosin or
      florfenicol. Fewer tulathromycin-treated cattle were removed from the group as
      "chronics" or "mortalities" at 28 days posttreatment (P < or = .014) in all three
      studies. Tulathromycin demonstrated superior efficacy compared with tilmicosin
      and florfenicol when treating groups of high-risk cattle before the onset of
      signs of BRD.

PMID- 16094564
TI  - Comparative efficacy of tulathromycin, tilmicosin, and florfenicol in the
      treatment of bovine respiratory disease in stocker cattle.
AB  - The therapeutic efficacy and field safety of tulathromycin were evaluated in
      stocker calves with undifferentiated bovine respiratory disease (BRD) in three
      field studies conducted over two consecutive grazing seasons in Nebraska. Eight
      hundred calves exhibiting clinical signs of BRD and with rectal temperatures of
      104 degrees F or higher were treated with tulathromycin (n = 340), florfenicol (n
      = 240), or tilmicosin (n = 220) and evaluated for approximately 60 days.
      Florfenicol and tilmicosin were administered as single SC injections according to
      labeled dosage. Tulathromycin was administered as a single SC injection of 2.5
      mg/kg. In all three studies, the cure rate of calves 60 days after treatment with
      tulathromycin was significantly higher (P < or = .05) than that of calves treated
      with florfenicol or tilmicosin. Suspected adverse reactions were not reported for
      any of the study drugs. Tulathromycin proved to be significantly more effective
      than either florfenicol or tilmicosin in the treatment of BRD in stocker calves.

PMID- 16094565
TI  - Comparative efficacy of tulathromycin versus florfenicol and tilmicosin against
      undifferentiated bovine respiratory disease in feedlot cattle.
AB  - Four studies conducted at feedlots in Greeley and Wellington, Colorado; Nebraska;
      and Texas compared the efficacy of tulathromycin to florfenicol or tilmicosin for
      the treatment of cattle with undifferentiated bovine respiratory disease (BRD)
      and subsequent feedlot performance and carcass characteristics. In each study,
      100 calves with BRD were treated with tulathromycin given SC at 2.5 mg/kg body
      weight. At the Greeley, CO, and Nebraska study locations, 100 calves were treated
      with florfenicol given SC at 40 mg/kg body weight, and at the Wellington, CO, and
      Texas study locations, tilmicosin was given SC at 10 mg/kg body weight. Cure
      rate, a derived variable that included assessments of mortality, rectal
      temperature, and attitude and respiratory scores from day 3 to day 28 and day 3
      through harvest, was the primary assessment of BRD efficacy. Cure rates of calves
      treated with tulathromycin were significantly (P < or = .009) higher than those
      calves treated with florfenicol. At Wellington, CO, the cure rate of calves
      treated with tulathromycin was significantly higher (P < or = .018) compared with
      tilmicosin-treated calves. The differences in cure rates between tulathromycin
      and tilmicosin treatment groups in the Texas study were not significantly
      different (P > .05). Tulathromycin was more efficacious in the treatment of
      undifferentiated BRD compared with florfenicol and, in one study, compared with
      tilmicosin.

PMID- 16094566
TI  - Evaluation of tulathromycin for the treatment of pneumonia following experimental
      infection of swine with Mycoplasma hyopneumoniae.
AB  - Tulathromycin was evaluated in the treatment of pneumonia in weaned pigs
      inoculated intranasally with Mycoplasma hyopneumoniae. Five days postchallenge,
      the pigs were randomized to treatment with a single IM administration of saline,
      a single IM administration of tulathromycin (2.5 mg/kg; day 0), or three IM
      administrations of enrofloxacin (5.0 mg/kg; days 0, 1, 2). Pigs were necropsied
      on day 12 or 13. Unchallenged controls remained healthy with no lung pathology.
      Compared with saline, coughing, mean lung lesion score, and proportional lung
      weight were significantly reduced and weight gain was significantly greater for
      tulathromycin-treated pigs (P < .05). Compared with enrofloxacin, there were no
      significant differences in proportional lung weight or weight gains, but coughing
      and lung lesion scores were greater for tulathromycin-treated pigs (P < .05).
      Tulathromycin was effective in the treatment of pneumonia following experimental
      infection with M. hyopneumoniae.

PMID- 16094567
TI  - Evaluation of the therapeutic activity of tulathromycin against swine respiratory
      disease on farms in Europe.
AB  - The clinical efficacy of tulathromycin in the treatment of natural outbreaks of
      swine respiratory disease (SRD) was evaluated at five European sites. Pigs (1 to
      6 months of age) exhibiting clinical signs of SRD were treated intramuscularly
      with tulathromycin (n = 247) at 2.5 mg/kg on day 0 versus either tiamulin (n =
      102) at 15 mg/kg on days 0, 1, and 2 (Germany, the Netherlands, and the United
      Kingdom) or florfenicol (n = 20) at 15 mg/kg on days 0 and 2 (France).
      Actinobacillus pleuropneumoniae, Pasteurella multocida, and Mycoplasma
      hyopneumoniae infections were the most frequently diagnosed pathogens. For both
      tulathromycin-treated animals and those treated with tiamulin or florfenicol,
      there were significant (P = .0001) reductions in mean rectal temperature and the
      severity of abnormal clinical signs on days 2 and 10 compared with day 0. There
      were no significant differences (P > .05) between treatments in average daily
      weight gain. Tulathromycin was found to be safe and highly effective in the
      treatment of natural outbreaks of SRD.

PMID- 16094568
TI  - Efficacy of tulathromycin injectable solution for the treatment of naturally
      occurring Swine respiratory disease.
AB  - Tulathromycin, a novel triamilide antimicrobial, was evaluated for treatment of
      swine respiratory disease (SRD) in field efficacy studies involving 720 pigs in
      six North American swine herds. In each study, feeder pigs with clinical SRD were
      randomly assigned in equal numbers to a group treated with tulathromycin given as
      a single injection at 2.5 mg/kg of body weight or to a saline-treated control
      group. Four of the studies included a third group treated with ceftiofur sodium
      for 3 consecutive days at 3 mg/kg of body weight. Pigs were treated on day 0 and
      evaluated for treatment response on day 7. In each study, 10 or more nontreated
      pigs and saline-treated pigs that did not respond to treatment underwent
      necropsies to obtain lung samples that were evaluated for SRD pathogens. The
      overall cure rate was 46.4% for saline-treated pigs, 71.1% for tulathromycin
      treated pigs, and 63.1% for ceftiofur-treated pigs. The cure rate for
      tulathromycin-treated pigs was significantly higher than for saline-treated pigs
      (P = .0116). Mortality from SRD occurred in 24 control pigs, seven tulathromycin
      treated pigs, and one ceftiofur-treated pig. The mortality rate was significantly
      lower for both the tulathromycin- and ceftiofur-treated pigs compared with those
      treated with saline (P = .0148 and P = .0195, respectively). Actinobacillus
      pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Mycoplasma
      hyopneumoniae, bacteria commonly associated with SRD, were isolated from SRD
      affected pigs. Under field conditions, tulathromycin injectable solution given as
      a single IM dose of 2.5 mg/kg of body weight was safe and effective in the
      treatment of SRD.

PMID- 16094569
TI  - Test yourself: the readers circle, oral and maxillofacial surgery self assessment
      tool and board recertification.

PMID- 16094570
TI  - Massachusetts General Hospital/Harvard MD Oral and Maxillofacial Surgery Program.

PMID- 16094571
TI  - Mandibular advancement by distraction osteogenesis for tracheostomy-dependent
      children with severe micrognathia.
AB  - PURPOSE: The purpose of this study was to evaluate mandibular lengthening by
      distraction osteogenesis (DO) to achieve decannulation of micrognathic children
      with "permanent" tracheostomies. PATIENTS AND METHODS: Using a retrospective
      chart review, patients were included who had 1 ) airway compromise/tracheostomy,
      2 ) micrognathia, 3 ) polysomnography-documented obstructive apnea, and 4 )
      mandibular advancement using DO. Excluded were 1 ) adults, 2 ) neonates without
      tracheostomy, and 3 ) patients with central apnea. Patient age, past medical
      history, age at tracheostomy, and distraction protocol were documented. Oxygen
      saturation, posterior airway space (in millimeters), and sella-nasion-B point
      (SNB) angle were recorded. The distraction protocol consisted of a latency of 48
      hours and a rate of 1 mm/day. RESULTS: There were 5 children, aged 2 to 14 years,
      who received a tracheostomy between ages 2 and 36 months for airway obstruction.
      All patients underwent bilateral mandibular distraction using semiburied,
      unidirectional devices. The average latency was 58 hours, the rate was 1 mm/day,
      the duration of fixation was 40 to 60 days, and the magnitude of advancement was
      23 mm. Healing was evaluated by clinical, radiologic, and ultrasound
      examinations. No complications were experienced. Mean follow-up was 3.2 years.
      Postdistraction sleep studies demonstrated no obstructive apneic events and a
      mean oxygen saturation of 98% (preoperative, 76%, P < .005). Cephalometric values
      improved: posterior airway space 4 to 14 mm; SNB 66 degrees to 72 degrees ( P <
      .005 for both variables). Four of the 5 patients have been successfully
      decannulated to date. CONCLUSIONS: The results of this preliminary study indicate
      that mandibular advancement by DO is a potentially viable treatment option for
      tracheostomy-dependent children with upper airway obstruction secondary to
      micrognathia.

PMID- 16094572
TI  - Traumatic subcutaneous emphysema of the face associated with paranasal sinus
      fractures: a prospective study.
AB  - PURPOSE: The purpose of this report was to review and analyze the epidemiologic
      features of traumatic subcutaneous emphysema (TSE) originating from frontal,
      nasoethmoidal, and maxillary facial injuries with sinusal involvement in the
      emergency room setting. PATIENTS AND METHODS: All patients with a fracture
      involving the paranasal sinuses were evaluated with regard to TSE occurrence.
      Data analysis extended to gender, age, etiology, fracture sites, TSE location,
      sinus involvement, treatment, and complications from April 1999 to December 2003.
      Evaluation methods included computed tomography scan and clinical evaluation.
      RESULTS: A total of 390 patients sustaining 458 paranasal sinus fractures were
      included. TSE was observed in 29 patients (7.43%) patients (male-female ratio of
      3.83:1, with a mean age of 36.71 +/- 15.71 years). The main etiologies were
      vehicle accidents and assaults. Isolated maxillary sinuses fractures were found
      in 17 cases (58.62%). Ethmoidal and maxillary fractures were associated with 9
      cases (31.03%), and 1 (3.45%) case had maxillary and frontal fractures together.
      Ethmoidal, maxillary, and frontal fractures were found concomitantly in 2 (6.90%)
      cases. Periorbital emphysema was the most prevalent site of presentation, and
      edema (86.21%) and bone deformities (79.31%) were the most frequent findings
      associated with TSE. Conservative treatment was the prevalent treatment choice
      (55.17%), and 1 complication because of persistent pain was noted. CONCLUSION:
      The results suggest that TSE of the face associated with paranasal sinus
      fractures maintained the clinical features of its fractures of origin. The
      ethmoidal sinuses were considered as the most prevalent etiologic site, and the
      periorbital region was responsible for addressing the higher incidence of SE
      following paranasal sinus fractures.

PMID- 16094573
TI  - Does creating a subperiosteal tunnel influence the periorbital edema and
      ecchymosis in rhinoplasty?
AB  - PURPOSE: The study goal was to determine whether creating a subperiosteal tunnel
      before lateral osteotomy had an effect on postoperative periorbital edema,
      ecchymosis, and subconjunctival ecchymosis. PATIENTS AND METHODS: Eighteen
      consecutive patients who underwent septorhinoplasty were included in the study.
      In all patients lateral osteotomies were carried out bilaterally, after creating
      a subperiosteal tunnel on a randomly chosen side and without creating a
      subperiosteal tunnel on the other side. The patients were seen on the second
      postoperative day, and a different surgeon who was unaware of the side with the
      periosteal tunnel determined the side of the face with more edema and ecchymosis.
      Subconjunctival ecchymosis was evaluated and recorded, as well. RESULTS: Creating
      subperiosteal tunnels before lateral osteotomy statistically increased
      periorbital ecchymosis. Although there was no statistically significant
      difference, creating subperiosteal tunnels also increased development and
      severity of subconjunctival ecchymosis and edema. CONCLUSIONS: We suggest
      performing lateral osteotomy without creating subperiosteal tunnels.

PMID- 16094574
TI  - Effectiveness of lymphoscintigraphic sentinel node detection for cervical staging
      of patients with squamous cell carcinoma of the head and neck.
AB  - PURPOSE: To evaluate the feasibility and staging ability of the sentinel node
      (SN) technique for patients with squamous cell carcinoma of the oral cavity or
      oropharynx and clinically negative necks. This prospective study compares the
      histopathologic status of the SN with that of the remaining neck dissection
      tissues. PATIENTS AND METHODS: Thirty previously untreated patients with T1 to T4
      squamous cell carcinoma of the oral cavity or oropharynx and clinically negative
      necks (N0) were included in the study. Injection of 99m Tic-radiolabeled sulfur
      colloid around the primary tumor and lymphoscintigraphy were performed the day
      before surgery. Intraoperatively, the SN(s) was localized with a gamma probe and
      removed during neck dissection. The tumor was resected at the same time. RESULTS:
      For 1 patient, lymphoscintigraphy revealed no SN. SN were identified in 29
      patients/37 necks. In 29 necks, there were no positive SN. In 5 patients, the SN
      was the only histopathologically positive node. In 1 patient, SN and other nodes
      in the remaining neck tissue were positive. There was 1 false negative case; the
      first case of the study, indicating the need for a learning curve for the
      technique. CONCLUSION: This prospective study shows that the SN is useful for the
      staging of N0 necks. The SN technique has the potential to decrease the need for
      neck dissections, which are usually performed in clinically negative necks, thus
      reducing both associated morbidity for patients and cost.

PMID- 16094575
TI  - Autonomic nervous system activity during autologous blood donation for
      orthognathic surgery.
AB  - PURPOSE: The aim of this study was to assess by means of power spectral analysis
      the immediate response of autonomic regulation that occurs with postural change
      from supine to sitting position (modified head-up tilt test [m-HUT]) during
      autologous blood donation (ABD) and postphlebotomy infusion. PATIENTS AND
      METHODS: We investigated 37 healthy adults who required preoperative ABD before
      elective orthognathic surgery. Measurements were conducted with m-HUT during ABD
      and postphlebotomy infusion. The data were analyzed using the maximum entropy
      method and the difference between supine and tilt was determined by analysis of
      variance. RESULTS: When m-HUT was conducted at the resting state, cardiac
      parasympathetic nervous activity was significantly decreased, whereas cardiac and
      vascular sympathetic nervous activities were significantly increased. When m-HUT
      was conducted following blood collection, cardiac parasympathetic nervous
      activity showed a tendency to increase, whereas vascular sympathetic nervous
      activity was significantly increased. These changes were not observed during
      postphlebotomy infusion. CONCLUSIONS: The m-HUT, which involves postural change
      from supine to sitting position, may be useful for observing autonomic nervous
      activity in the clinical setting. ABD carries the risk of imbalance of autonomic
      regulation. However, postphlebotomy infusion may reduce this imbalance.

PMID- 16094576
TI  - Telemedicine in maxillofacial trauma: a 2-year clinical experience.
AB  - PURPOSE: The authors report the 2-year experience of use of the PATATRAC
      telemedicine system in managing maxillofacial trauma. MATERIALS AND METHODS:
      Thirty-five regional hospitals on-line with PATATRAC in the period from January
      2002-January 2004 have sent 18 consultations (11 men and 7 women) to the
      Maxillofacial Surgery Division of San Giovanni Battista Hospital in Turin for
      telemedicine evaluation of patients with maxillofacial trauma. RESULTS: Only 50%
      of the consultations (9 patients) sent via PATATRAC indicated maxillofacial
      treatment, and only one case resulted in immediate transfer. Of the remaining 8
      transfers, 2 patients were transferred after treatment of associated lesions in
      the receiving hospital, and the other 6 patients were transferred as scheduled
      based on the availability of beds in the specialist center. CONCLUSIONS: The
      results obtained, despite the poor number of telemedicine maxillofacial
      consultations, have mainly proved the usefulness of PATATRAC in drastically
      reducing expensive and unnecessary transfers of maxillofacial patients, without
      indications for either immediate or deferred treatment, thus also avoiding
      discomfort to the patient with other injuries.

PMID- 16094577
TI  - The American Association of Oral and Maxillofacial Surgeons Age-Related Third
      Molar Study.
AB  - PURPOSE: The purpose of this investigation was to assess the frequency of
      complications of third molar surgery, both intraoperatively and postoperatively,
      specifically for patients 25 years of age or older. MATERIALS AND METHODS: This
      prospective study evaluated 3,760 patients, 25 years of age or older, who were to
      undergo third molar surgery by oral and maxillofacial surgeons practicing in the
      United States. The predictor variables were categorized as demographic (age,
      gender), American Society of Anesthesiologists classification, chronic conditions
      and medical risk factors, and preoperative description of third molars (present
      or absent, type of impaction, abnormalities or association with pathology).
      Outcome variables were intraoperative and postoperative complications, as well as
      quality of life issues (days of work missed or normal activity curtailed).
      Frequencies for data collected were tabulated. RESULTS: The sample was provided
      by 63 surgeons, and was composed of 3,760 patients with 9,845 third molars who
      were 25 years of age or older, of which 8,333 third molars were removed. Alveolar
      osteitis was the most frequently encountered postoperative problem (0.2% to
      12.7%). Postoperative inferior alveolar nerve anesthesia/paresthesia occurred
      with a frequency of 1.1% to 1.7%, while lingual nerve anesthesia/paresthesia was
      calculated as 0.3%. All other complications also occurred with a frequency of
      less than 1%. CONCLUSION: The findings of this study indicate that third molar
      surgery in patients 25 years of age or older is associated with minimal
      morbidity, a low incidence of postoperative complications, and minimal impact on
      the patients quality of life.

PMID- 16094578
TI  - Characterization of patients with disc displacement without reduction
      unresponsive to nonsurgical treatment: a preliminary study.
AB  - PURPOSE: Arthrocentesis and arthroscopic lysis and lavage have been described as
      effective treatment modalities for temporomandibular joint (TMJ) disc
      displacement without reduction (DDw/oR). More commonly, nonsurgical intervention
      is offered as the desired first-line treatment; however, a certain group of
      DDw/oR patients receiving nonsurgical treatment may remain unresponsive, thereby
      prolonging suffering and treatment dissatisfaction. The purpose of this study is
      to characterize these nonresponders by evaluating the characteristic pretreatment
      findings peculiar to this group. PATIENTS AND METHODS: This retrospective study
      was based on the review of pretreatment clinical and magnetic resonance imaging
      (MRI) findings of 52 DDw/oR patients who were treated with stabilization
      appliance, jaw-stretching exercise, and nonsteroidal anti-inflammatory
      medication. On the last treatment visit, each patient was classified as either a
      responder (R) or nonresponder (NR) based on the satisfaction or dissatisfaction
      with the treatment received, respectively. Pretreatment data were then examined
      and analyzed by logistic regression to identify which clinical and MRI findings
      were specifically related to the NR group. RESULTS: Logistic regressions
      indicated that NR had significantly higher odds ratio for pretreatment pain-free
      mouth opening of less than 30 mm (odds ratio [OR] = 7.385), "stuck" disc (OR =
      4.521), and unchanged disc shape during mouth opening (OR = 4.050). Multiple
      logistic regression analyses revealed that these factors combined gave the
      highest likelihood ratio of 15.90 ( P = .001), indicating a strong possibility
      that these factors are associated with the NR group. CONCLUSIONS: Nonresponders
      can be characterized by their pretreatment pain-free mouth opening (<30 mm) in
      combination with MRI confirmation of "stuck" disc and unchanged disc shapes
      during mouth opening.

PMID- 16094579
TI  - Comparison of the severity of bilateral Le Fort injuries in isolated midface
      trauma.
AB  - PURPOSE: The Le Fort classification pattern established in 1901 by the French
      surgeon Rene Le Fort is commonly used in describing midface fractures. This
      frequently used classification system is based on predictable patterns of midface
      fractures initially described for blunt trauma. The purpose of this study was to
      compare the profile and outcome of patients with isolated bilateral Le Fort I,
      II, and III fractures. PATIENTS AND METHODS: All patients presenting to the
      emergency department (ED) at Legacy Emanuel Hospital (Level I trauma center) in
      Portland, OR, between December 1990 and December 2003 with isolated bilateral Le
      Fort I, II, or III fractures with or without concomitant nonfacial injuries were
      identified retrospectively using the Hospital Trauma Registry. Patients were
      classified into study groups I (n = 22), II (n = 22), or III (n = 23)
      corresponding to the Le Fort classification, respectively. RESULTS: Sixty-seven
      patients had a diagnosis of isolated bilateral Le Fort I, II, or III fracture.
      The average Injury Severity Score (ISS) and hospital length of stay were 18.8 +/-
      8.9 and 9.5 +/- 11.9 days, respectively. Blood alcohol was detected in 19
      patients. Sixty-four injuries (95.5%) were secondary to blunt trauma, and the
      remaining 3 (4.5%), penetrating injuries. More than half of the patients (n = 35,
      52.2%) were admitted to the intensive care unit (ICU), 18 patients (26.8%) were
      transferred to the hospital trauma ward from the ED, and 14 patients (20.9%) were
      taken directly to the operating room. Fifteen (22.4%) patients required a
      tracheostomy secondary to their maxillofacial injuries. A statistically
      significant difference in the ISS was detected between patients with Le Fort I
      versus those with II or III injuries ( P < .0001). Patients with Le Fort II or
      III fractures had a significantly higher probability of ICU admission or
      immediate operative intervention. Ten patients (43.5%) with Le Fort III injuries
      required tracheostomy versus 3 patients (13.6%) with Le Fort I, and 2 patients
      (9.1%) with Le Fort II injuries. This was statistically significant. None of the
      patients with Le Fort I injuries had a negative outcome (death); however, 1
      patient with Le Fort II injuries (4.5%) and 2 with Le Fort III injuries (8.7%)
      had a negative outcome. No statistically significant differences or emerging
      trends were observed among the 3 groups for age, gender, length of stay, number
      of operations, and number of associated injuries. CONCLUSIONS: Patients with
      higher Le Fort injuries are characterized by an overall greater severity of
      injuries as measured by the ISS and the more frequent need for a surgical airway.
      Patients with Le Fort III injuries have a higher chance of requiring
      neurosurgical intervention or of experiencing vision-threatening ocular trauma.
      Immediate operative intervention and/or ICU care is more frequently indicated in
      these patients.

PMID- 16094580
TI  - Pain medication as an indicator of interference with lifestyle and oral function
      during recovery after third molar surgery.
AB  - Purpose This study was designed to assess the impact of taking pain medications,
      as a more comprehensive indicator of perceived pain, on the extent of
      interference with lifestyle and oral function during recovery after third molar
      surgery. Patients and Methods Recovery data after the removal of 4 third molars
      were available for patients enrolled in an institutional review board-approved,
      prospective, multicenter clinical trial. A self-administered health-related
      quality of life instrument, designed to assess a patients perception of recovery
      for pain, lifestyle, and oral function, was completed each postsurgery day (PSD)
      for 14 days. Taking pain medications was a proxy for a patients perceived level
      of pain, adding a more sensitive behavioral component to the report of pain. Each
      PSD day, the patients who thought that their pain was sufficient to require
      taking medications (an opioid, a nonsteroidal anti-inflammatory, or the
      combination) were compared with patients not taking pain medications. The extent
      of interference in lifestyle (daily activity, social life, recreation, sleep) and
      in oral function (eating, chewing, mouth opening) as self-reported on a scale of
      1 (no trouble) to 5 (lots of trouble) were compared for those taking and not
      taking medications using Cochran-Mantel-Haenszel row mean statistics ( P < .05).
      Results The 445 study patients were mostly female (63%) and white (86%). Median
      age was 20 years (IQ, 18, 24 years). Median surgery time was 30 minutes (IQ, 20,
      40 minutes). Both mandibular third molars were below the occlusal plane in 60%.
      Almost all patients took pain medication on PSD 1. By PSD 7, 48% of patients were
      taking pain medication, decreasing to 20% by PSD 11. Patients with pain
      sufficient to take an analgesic reported a greater extent of interference for all
      lifestyle and oral function measures. Recovery was significantly delayed for PSD
      2 through 14 for patients who took medications ( P < 0.01). Recovery for females
      taking pain medications was significantly delayed compared with that for males.
      Conclusions Patients with pain sufficient to prompt taking pain medications were
      likely to report interference with recovery for lifestyle and oral function. A
      patients choice to take pain medication appears to be a better indicator of a
      patients perceived pain and the impact of that pain on recovery than numerical
      pain scales. This method provides more sensitive behavioral information during
      the period of recovery after third molar removal.

PMID- 16094581
TI  - A comparison of patient satisfaction and objective assessment of neurosensory
      function after trigeminal nerve repair.
AB  - PURPOSE: The purpose of this study was to compare objective and subjective
      assessments of neurosensory function after trigeminal nerve repair. METHODS: This
      was a retrospective cohort study using a sample of patients who underwent
      surgical repair of trigeminal nerve injuries. The primary study variables were
      categorized as objective or subjective. The objective variable was the change in
      neurosensory examination between preoperative and 1-year postoperative visits.
      Neurosensory status was measured using an ordinal scale ranging from anesthetic
      (0) to normal (4). Subjective variables included patient satisfaction with the
      nerve repair and patient assessment of injury-related oral dysfunction.
      Demographic, anatomic, and operative variables were also collected. Appropriate
      univariate and bivariate statistics were computed. RESULTS: The sample was
      composed of 19 patients (14 female, 17 Caucasian) who had trigeminal nerve repair
      (17 lingual, 2 inferior alveolar). The mean duration between injury and repair
      was 4.5 +/- 2.3 months; between repair and postoperative assessment was 11.9 +/-
      0.9 months. The mean change in neurosensory status was 1.3 +/- 1.0 levels. The
      majority of patients (63.1%) rated their satisfaction with the outcome of
      treatment as "good" to "excellent." There was a statistically significant
      correlation between change in neurosensory status and patient satisfaction (rho =
      0.86; P < .01). CONCLUSION: There is evidence of a strong correlation between
      improvement in the neurosensory examination following trigeminal nerve repair and
      patient satisfaction with the surgical outcome 1-year postoperatively. Patients
      who experience greater neurosensory improvement also report lower frequencies of
      related oral dysfunction.

PMID- 16094582
TI  - Long-term outcome assessment for lingual nerve microsurgery.
AB  - OBJECTIVE: A retrospective study was undertaken to investigate the clinical
      outcomes resulting from the microsurgical repair of lingual nerve injuries. The
      study was based on patient chart review. PATIENTS AND METHODS: A total of 20
      patients referred to the principal investigator (V.B.Z.), with a diagnosis of
      lingual nerve injury who underwent trigeminal nerve microsurgery during a 3-year
      period (1999 to 2002), were entered in this study. All patients received a
      complete history and physical examination, and thorough preoperative and
      postoperative neurosensory testing to evaluate clinical response to hot, cold,
      cotton wisp, vibration, 2-point discrimination, directional stroke, and fine
      touch as determined by Von-Frey filaments. RESULTS: All patients underwent an
      external neurolysis procedure in combination with an internal neurolysis, neuroma
      excision, or primary neurorrhaphy under microscopic guidance depending on the
      intraoperative findings. The average time from injury to surgery was 8 months.
      The patients were followed for an average of 9 months after surgery, and
      assessment was based on the patients subjective experience as well as
      standardized neurosensory testing. Eighteen patients (90%) had some improvement
      in neurosensory function and 2 patients (10%) reported no improvement. One of the
      patients exhibiting no clinical improvement had a prolonged delay in seeking
      treatment, and the distal nerve could not be localized intraoperatively. Most
      patients were operated on between 2.5 and 7 months after injury, and there was no
      statistical difference in outcome as a function of the time from injury to repair
      in this group of patients. This subgroup of responding patients averaged at least
      50% improvement in neurosensory function. CONCLUSION: Microsurgical repair of
      lingual nerves provides moderate to significant improvements in clinical sensory
      function and is a useful option in treating affected individuals, especially when
      implemented soon after injury.

PMID- 16094583
TI  - Subjective outcomes following sural nerve harvest.
AB  - PURPOSE: The goal of this study was to assess subjective patient recovery of
      donor site sensory deficit following sural nerve harvest for trigeminal nerve
      repair surgery. PATIENTS AND METHODS: A review of 42 consecutive sural nerve
      graft patient records yielded 26 patients, at least 20 months following sural
      nerve grafting for trigeminal nerve repair, who participated in a telephone
      questionnaire survey to assess subjective outcomes. The association between donor
      site outcome and other factors, including nerve graft recovery, age, gender,
      pain, cold sensitivity, scar cosmesis and tactile sensitivity, and legal
      involvement were analyzed, and presurgical and present levels of donor and nerve
      graft site sensibility were compared. RESULTS: The perceived area of donor site
      sensory deficit decreased significantly over time. Postoperative donor site pain
      and cold sensitivity at low levels were reported by few patients, and the
      majority have completely resolved. Most patients reported no problems with scar
      cosmesis or pain. There was a moderate agreement between donor site recovery and
      nerve graft recovery (kappa = 0.32). Few patients reported satisfaction with one
      site and not the other or complete dissatisfaction with both sites. Other factors
      such as age, gender, or legal involvement were not found to correlate with
      satisfaction level. CONCLUSIONS: The use of a questionnaire for subjective
      assessment of neurosensory recovery following nerve graft repair yields outcomes
      information that is generally not considered in the traditional clinical patient
      assessment. The majority of patients tolerate sural nerve harvest without
      significant donor site morbidity.

PMID- 16094584
TI  - Normal and abnormal temporomandibular joint disc and posterior attachment as
      depicted by magnetic resonance imaging in symptomatic and asymptomatic subjects.
AB  - PURPOSE: This investigation provides a detailed assessment of the morphologic and
      signal intensity changes of the temporomandibular joint disc and posterior disc
      attachment as depicted by magnetic resonance imaging in symptomatic versus
      asymptomatic subjects. PATIENTS AND METHODS: Sixty-one asymptomatic volunteers
      and 58 symptomatic subjects were imaged using a 1.5 tesla magnetic resonance
      system utilizing bilateral high-resolution surface coils with the jaw in the
      closed and maximal opened position. Disc shape and signal intensity
      characteristics were tabulated along with a detailed assessment of the various
      regions of the disc posterior attachment in a blinded fashion as to
      symptomatology. RESULTS: Deformity of the disc was noted in 34 of 116 (29.3%) of
      joints in patients and in 5 of 122 (4%) of joints of volunteers ( P < .0005; chi
      square test). There was a large region of increased signal intensity in the
      posterior band of the disc on proton- or T1- weighted images in 13 of 116 (11.2%)
      joints in patients versus 1 of 122 (0.8%) joints in asymptomatic subjects ( P <
      .0005). In all joints with disc displacement with or without reduction, the
      temporal posterior attachment was visualized in only 43.5% in the closed jaw
      position ( P < .0005 versus all normal joints) and in 30.4% ( P < .0005 versus
      all normal joints) in the open jaw position. CONCLUSION: Magnetic resonance
      allows an in vivo characterization of the fine structural details of the disc and
      the disc posterior attachment, separating normal from internal derangement
      temporomandibular joints.

PMID- 16094585
TI  - The analgesic efficacy of intravenous versus oral tramadol for preventing
      postoperative pain after third molar surgery.
AB  - PURPOSE: The aim of this study was to compare the analgesic efficacy of single
      dose preoperative intravenous versus oral tramadol for preventing pain after
      third molar surgery. PATIENTS AND METHODS: Seventy-two patients undergoing
      elective third molar surgery were randomized to receive either intravenous (n =
      36) or oral (n = 36) tramadol 50 mg. The intravenous group received an oral
      placebo capsule followed by intravenous tramadol 50 mg preoperatively. The oral
      tramadol group received a 50-mg oral tramadol capsule followed by intravenous
      placebo saline preoperatively. In both groups, a standard intravenous sedation
      technique was administered and the impacted third molars were removed under local
      anesthesia. The difference in postoperative pain was assessed by 4 primary end
      points: hourly pain intensity as measured by a 100-mm visual analog scale for 8
      hours, time to rescue analgesic, postoperative acetaminophen consumption, and a 5
      point global assessment scale (0 = poor, 1 = fair, 2 = good, 3 = very good, and 4
      = excellent). RESULTS: Throughout the 8-hour investigation period, patients
      reported significantly lower pain intensity scores in the intravenous versus oral
      group (15.9 +/- 9.6 mm versus 36.9 +/- 17.2 mm, P = .03). Patients also reported
      significantly longer time to rescue analgesic (7.0 hours versus 3.5 hours, P =
      .00001), lesser postoperative acetaminophen consumption (1,823 +/- 1,266 mg
      versus 3,558 +/- 1,418 mg, P = .000006), and better global assessment (2.6 +/-
      0.9 versus 1.1 +/- 0.8, P = .01) for the intravenous versus oral group.
      CONCLUSIONS: We conclude that preoperative intravenous tramadol is superior to
      oral tramadol for preventing postoperative pain following third molar surgery.
      However, it should be noted that there is a difference in the bioavailability
      between the 2 formulations of up to 30%, which may explain the findings.

PMID- 16094586
TI  - The relationship between enophthalmos, linear displacement, and volume change in
      experimentally recreated orbital fractures.
AB  - PURPOSE: The purpose of this investigation was to establish the relationship
      between enophthalmos, linear displacement, and volume change for various patterns
      of experimentally recreated orbital fractures. MATERIALS AND METHODS: We
      fabricated an experimental apparatus that permitted uniform displacement of
      simulated orbital wall fractures. Measurements of linear displacement, volume
      change, and degree of simulated enophthalmos were taken for 1- and 2-walled
      displacements. Means and standard deviations were derived, and analysis of
      variance was used to compare means for statistically significant differences ( P
      < .05) between groups and among major categories. RESULTS: No statistically
      significant differences were found for any uniform displacement caused by 1
      walled defects or for any given displacement caused by 2-walled defects The
      linear coefficient for displacement and enophthalmos or for displacement and
      volume change approached 1.0 for all groups (range, 0.9802 to 0.9999). However,
      statistically significant differences in mean enophthalmos and mean volume change
      at uniform displacements were found between 1- and 2-walled defects. CONCLUSIONS:
      Displacement of 1- and 2-walled orbital defects results in a direct and linear
      change in both orbital volume and enophthalmos, regardless of the location of the
      defect.

PMID- 16094587
TI  - Prospective multicenter comparison of 4 temporomandibular joint operations.
AB  - PURPOSE: This study was designed to compare the outcomes of 4 operations used for
      the treatment of painful temporomandibular joints with an internal derangement.
      PATIENTS AND METHODS: A prospective, controlled study of arthroscopy,
      condylotomy, discectomy, and disc repositioning was conducted at 3 sites. All
      sites used the same inclusion and exclusion criteria. Trained, independent
      examiners assessed pain, diet, and range of motion before operation and 1 month
      and 1 year after operation. RESULTS: There were statistically significant
      reductions in the amount of pain ( P < .001) and daily time in pain ( P < .001)
      that were similar for all 4 operations 1 month and 1 year after the procedures.
      The degrees of change after each of the 4 procedures were not statistically
      different from each other (amount: P = .453 and time: P = .416). Ability to chew,
      as measured by diet visual analog scale, was substantially improved 1 year after
      operation ( P < .001). The degrees of change for diet at 1 year also were not
      different from each other ( P = .314). There were, however, statistically
      significant differences ( P < .05) in range of motion that varied with procedure.
      CONCLUSIONS: All 4 operations were followed by marked improvements in pain and
      diet. The amounts of improvement varied slightly by operation, but these
      differences were not statistically significant. There were small but
      statistically significant differences between procedures for range of motion. If
      these findings are confirmed, they have an important implication for procedure
      selection.

PMID- 16094588
TI  - Strength analysis of titanium and resorbable internal fixation in a mandibulotomy
      model.
AB  - PURPOSE: Mandibulotomy is used to access various tumors of the tongue base,
      posterior oral cavity, pharynx, parapharyngeal space, and cranial base. Internal
      fixation using titanium plates and screws is the most common method of
      stabilization. These have the potential for interference with radiotherapy
      delivery. This in vitro study compares the strength of titanium and resorbable
      internal fixation in a mandibulotomy model by analyzing the force required for
      plate and screw breakage. MATERIALS AND METHODS: Red oak wood board was used to
      simulate the mandible. Titanium and resorbable plates and screws in various
      configurations were used to stabilize pieces of the wood. They were arranged in 6
      different groups. The specimens were individually tested with a vertical load,
      while the test machine recorded the force-versus-displacement behavior
      automatically. RESULTS: Plate type and configuration affected the applied load
      required to induce displacement of the simulated mandibulotomy. Heating and
      cooling the resorbable plates prior to strength testing also affected the load
      versus-displacement curve. CONCLUSIONS: Overall, the titanium system we studied
      exhibited greater resistance to deformation from a vertical load than did the
      resorbable plate groups.

PMID- 16094589
TI  - Correlation of papilla to crestal bone levels around single tooth implants in
      immediate or delayed crown protocols.
AB  - PURPOSE: The purposes of this study are to determine if there is a difference in
      the papilla fill between implant and teeth comparing immediate provisionalized
      and delayed single tooth implant restorations, and to determine the relationships
      between the vertical and horizontal bone levels to papilla filling the inter
      dental region with single implant restorations. PATIENTS AND METHODS: Two groups
      of patients treated with single tooth implant restorations were prospectively
      followed. One group had immediate provisionalization of their implants, and the
      second group a delayed approach. Serial radiographs and photographs were used to
      collect bone level measurements for the vertical distance between contact point
      to bone level on the adjacent tooth, implant, and the midcrestal region. The
      horizontal distances were also recorded. Papilla morphology was scored 1 through
      4. Univariate analysis was used to evaluate the relationships between bone levels
      and papilla morphology. RESULTS: There were no differences between papilla or
      bone levels comparing immediate provisionalization to delayed approaches. There
      were significant ( P < .05) relationships between the vertical distance from
      contact point to bone levels, with the distance from the contain point to the
      adjacent tooth the distance most critical to papilla maintenance. There were no
      significant relationships between horizontal distance and papilla maintenance.
      CONCLUSION: As the distance from the contact point to the implant increased,
      there was a significant chance of loss of papilla. There was no difference
      between delayed or immediate provisionalization and papilla scores. The
      horizontal distance from adjacent tooth bone level did not correlate to papilla
      score within the range of clinically relevant distances.

PMID- 16094590
TI  - The anterior palate as a donor site in maxillofacial bone grafting: a
      quantitative anatomic study.
AB  - PURPOSE: The goal of this study was to quantify the amount of bone graft material
      present in the anterior palate site. MATERIALS AND METHODS: Twenty-one fixed
      cadavers, dentulous and edentulous maxilla, were studied. Osteotomies were
      performed in monocortical fashion, 2 mm from the bone crest and parallel to the
      tooth axis and 3 mm from the incisive foramen at the midline. The bur penetration
      was indicated by radiographic index. The amount of the corticocancellous block
      was then measured with displacement volumetric technique. RESULTS: The average
      volume obtained were 2.03 mL in dentate and 2.40 mL in edentulous patients ( P =
      .2135, not significant between the 2 groups). CONCLUSIONS: Based on the results
      of this study, it is apparent that the anterior region of the palate can be
      reliably selected as the donor site in the oral and maxillofacial reconstructive,
      implantology, and periodontal regeneration procedure.

PMID- 16094591
TI  - Limited painful mouth opening.

PMID- 16094592
TI  - Distraction osteogenesis in management of pediatric airway: evidence to support
      its use.

PMID- 16094593
TI  - Airway management in babies with micrognathia: the case against early
      distraction.

PMID- 16094594
TI  - Peripheral primitive neuroectodermal tumor of the mandible with cytogenetic and
      molecular biology aberrations.

PMID- 16094595
TI  - Extra-abdominal fibromatosis of the cheek: report of a case.

PMID- 16094596
TI  - Primary de novo intraosseous carcinoma: report of two cases.

PMID- 16094597
TI  - Squamous cell carcinoma arising in a residual odontogenic cyst: case report.

PMID- 16094598
TI  - Efficacy of vancomycin-impregnated cement beads for the treatment of MRSA
      infection of failed graft tissue at the mandible.

PMID- 16094599
TI  - An alternative method for vermilion reconstruction after resection of hemangiomas
      of the lip.
AB  - PURPOSE: We describe a method for symmetrical vermilion reconstruction after
      resection of hemangiomas of the lip. PATIENTS AND METHODS: Four patients
      underwent vermilion reconstruction after resection of large cavernous hemangiomas
      of the lip. This reconstruction technique employed 3 basic components: 1 ) labial
      mucosal advancement flap, 2 ) orbicularis oris muscle flap, if necessary, and 3 )
      free mucosal graft. RESULTS: All patients successfully underwent the planned
      procedures without significant complications. Symmetrical profiles of vermilion
      of the lip were achieved in all cases, even when an extended excision had been
      performed. CONCLUSIONS: We have found that the combination of labial mucosal
      advancement flaps, with or without muscular flaps, and free mucosal grafts
      provides excellent esthetic outcomes with a low complication rate. This method
      should be incorporated into the surgical techniques for symmetrical
      reconstruction after resection of hemangiomas of the lip.

PMID- 16094600
TI  - Towel clip reduction of the depressed zygomatic arch fracture.

PMID- 16094601
TI  - Offshore medical degree, onshore medical license.

PMID- 16094602
TI  - Osteonecrosis of the jaws: a complex group of disorders.

PMID- 16094603
TI  - Oral to nasal endotracheal tube exchange following reconstructive surgery of the
      oral cavity by means of vascularized free flaps.

PMID- 16094604
TI  - Histiocytic giant cell formation showing sperm phagocytosis on papanicolaou
      smear.

PMID- 16094605
TI  - Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell
      signaling.
AB  - Regulation, recognition and cell signaling involve the coordinated actions of
      many players. To achieve this coordination, each participant must have a valid
      identification (ID) that is easily recognized by the others. For proteins, these
      IDs are often within intrinsically disordered (also ID) regions. The functions of
      a set of well-characterized ID regions from a diversity of proteins are presented
      herein to support this view. These examples include both more recently described
      signaling proteins, such as p53, alpha-synuclein, HMGA, the Rieske protein,
      estrogen receptor alpha, chaperones, GCN4, Arf, Hdm2, FlgM, measles virus
      nucleoprotein, RNase E, glycogen synthase kinase 3beta, p21(Waf1/Cip1/Sdi1),
      caldesmon, calmodulin, BRCA1 and several other intriguing proteins, as well as
      historical prototypes for signaling, regulation, control and molecular
      recognition, such as the lac repressor, the voltage gated potassium channel, RNA
      polymerase and the S15 peptide associating with the RNA polymerase S-protein. The
      frequent occurrence and the common use of ID regions in important protein
      functions raise the possibility that the relationship between amino acid
      sequence, disordered ensemble and function might be the dominant paradigm for the
      molecular recognition that serves as the basis for signaling and regulation by
      protein molecules.

PMID- 16094606
TI  - Protein expression profiling identifies maspin and stathmin as potential
      biomarkers of adenoid cystic carcinoma of the salivary glands.
AB  - Adenoid cystic carcinoma (ACC) is one of the most common malignant tumors of the
      salivary glands. It tends to grow slowly but is associated with a poor prognosis
      compared to other malignant salivary gland tumors. To identify specific markers
      of ACC, we examined protein expression profiling in ACC xenograft and normal
      salivary glands (NSG) using fluorescent 2-dimensional differential in-gel
      electrophoresis (2-D-DIGE), an emerging technique for comparative proteomics,
      that improves the reproducibility and reliability of differential protein
      expression analysis between the samples. To identify the proteins, matrix
      assisted laser desorption/ionization time-of-flight peptide mass fingerprinting
      was carried out. Using these strategies, we detected 4 upregulated proteins and 5
      downregulated proteins in ACC xenograft. Maspin and stathmin were selected for
      further analyses. Western blotting and immunohistochemical staining showed a
      higher expression of these proteins in ACC xenograft and clinical ACC tissue
      compared to NSG. Furthermore, Expression of these proteins was correlated with
      the histologic grading of ACC (n = 10). Therefore, our data indicate that maspin
      and stathmin may be not only useful biomarkers of ACC but also markers of
      biologic behavior in this tumor.

PMID- 16094607
TI  - Methylation of the O6-methylguanine-DNA methyltransferase promoter suppresses
      expression in mouse skin tumors and varies with the tumor induction protocol.
AB  - Hypermethylation of CpG sites within the promoter region of the O6-methylguanine
      DNA methyltransferase (MGMT) gene occurs frequently in human cancer, preventing
      both MGMT expression and repair of alkylation damage. To assess the role of MGMT
      in the development of mouse skin tumors induced by initiation-promotion
      protocols, methylation of the MGMT promoter was examined in tumor DNA using
      methylation-specific PCR. To determine whether MGMT promoter methylation was
      affected by the tumor induction protocol, tumors were initiated by N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenz[a]anthracene (DMBA) and
      promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA) or mezerein. Although the
      MGMT promoter was not methylated in normal skin, promoter methylation was found
      in 56 of 136 papillomas (41.2%) and in 19 of 37 squamous cell carcinomas (51.4%).
      When methylation of the MGMT promoter was compared in the 4 treatment groups,
      hypermethylation was found more frequently in tumors initiated by DMBA and
      promoted by mezerein, a protocol associated with a high frequency of malignant
      conversion. Methylation was found in some tumors as early as 5 weeks after
      initiation, but the methylation frequency increased with time. MGMT promoter
      methylation reduced MGMT expression as determined by immunohistochemistry.
      Although MGMT promoter methylation was not generally correlated with ras
      mutations, the frequency of MGMT methylation was higher in MNNG-initiated,
      mezerein-promoted papillomas with mutations in Ha-ras compared to papillomas with
      Ki-ras. Methylation of the MGMT promoter, associated with reduced MGMT
      expression, is found in nearly half of mouse skin tumors, but varies with both
      the tumor initiator and tumor promoter, and may be a key step in the progression
      from papillomas to carcinomas.

PMID- 16094608
TI  - Re: "Obesity and hormone-dependent tumors: cohort and co-twin control studies
      based on the Swedish twin registry".

PMID- 16094609
TI  - Diagnostic model for sensitization in workers exposed to occupational high
      molecular weight allergens.
AB  - BACKGROUND: Occupational allergy has great impact on workers exposed to high
      molecular weight (HMW) allergens. The present study is aimed to develop and
      validate a generic diagnostic model for sensitization to HMW allergens, defined
      as positive IgE. METHODS: The model was developed in pooled data from Dutch
      laboratory animal (LA) workers and bakers using logistic regression analysis.
      Validity was assessed internally by bootstrapping procedure, and externally in
      British LA workers. RESULTS: The model included working hours/week, work-related
      symptoms, total IgE, and IgE to common allergen. Significant interactions between
      the type of work and the predictors resulted in different scores for LA workers
      and bakers. Internal and external validation showed that the model was
      satisfactorily calibrated and discriminated between workers at high and low risk
      of being sensitized. CONCLUSIONS: It is possible to develop a generic model for
      sensitization to occupational HMW allergens. However, the weighing of predictors
      differs across specific work environments.

PMID- 16094610
TI  - Mortality of iron and steel workers in Korea.
AB  - BACKGROUND: The mortality experience of iron and steel workers from modern plants
      in developing countries has not been extensively described. METHODS: Mortality at
      two Korean iron and steel manufacturing complexes was analyzed using Poisson
      regression methods with both direct and indirect standardization. Work histories
      were linked with a national mortality registry. Workers (44,974) hired beginning
      in 1968 were followed from 1992 to 2001. RESULTS: The 806 deaths observed during
      10 years of follow-up comprised 2% of the population at risk and represented a
      large healthy worker effect (HWE) for all causes (SMR = 0.59, 95% CI = 0.55-0.63)
      and for cancer (SMR = 0.79, 95% CI = 0.70-0.90). Mortality at subsidiaries was
      considerably higher than at the parent plants (SRR = 1.71, 95% CI = 1.47-1.99).
      Relative mortality rates declined with employment duration: > 20 years had
      significantly reduced mortality (SRR = 0.59, 95% CI = 0.43-0.82) compared to
      duration < 1 year (test for trend: P = 0.0006). Fatal injury deaths in the first
      year were highly elevated (SMR = 3.10, 95% CI = 2.17-4.26) declining to less than
      that expected after 5 years. Cancer mortality was elevated in stainless steel
      production (SRR = 3.26, 95% CI = 1.37-6.49) and overall mortality was elevated
      for work in plant maintenance departments (SRR = 1.17, 95% CI = 1.00-1.37),
      particularly for fatal injuries (SRR = 1.67, 95% CI = 1.29-2.14). All-cause
      mortality increased with employment duration in the steel-production departments,
      as did fatal injuries in material handling/construction. CONCLUSIONS: This
      steelworker cohort exhibits excess mortality in some process areas. More detailed
      retrospective exposure assessment and future follow-up of this cohort will better
      define health risks in the modern iron and steel manufacturing.

PMID- 16094611
TI  - Respiratory outcomes among South African coal miners at autopsy.
AB  - BACKGROUND: Studies of dose-response relationships between respiratory outcomes
      at autopsy and coal dust exposure are limited. The Pathology Automation System
      (PATHAUT) database of South African miners, is one of the largest autopsy
      databases of occupational lung disease. This study described the prevalence of
      respiratory outcomes among South African coal miners at autopsy, and determined
      whether dose response relationships existed between emphysema and exposure.
      METHODS: Autopsies conducted from 1975 to 1997 on coal miners with exclusive coal
      mining exposure and having exposure duration information (n = 3,167) were
      analyzed from PATHAUT. Logistic regression was used to determine relationships
      between exposure and outcomes, controlling for race, smoking and age on a subset
      for whom smoking history was available (n = 725). RESULTS: The mean duration of
      exposure was 11.0 years. Most were black miners (75.3%) with significant
      differences in the mean ages of black and white miners (37.9 and 55.3 years,
      respectively). Only 22.9% of cases had information on smoking. The prevalence of
      silicosis, tuberculosis (TB), coal workers' pneumoconiosis (CWP), and moderate
      and marked emphysema were 10.7%, 5.2%, 7.3%, and 6.4%, respectively. All
      diseases, except TB, were associated with exposure duration. Black miners had 8.3
      and 1.2 fold greater risks for TB and CWP, respectively, than white miners. White
      miners had an increased risk of 1.4 and 5.4 for silicosis and moderate to marked
      emphysema, respectively. In models unadjusted for age, and including smoking,
      moderate to marked emphysema was strongly associated with exposure duration (OR =
      3.4; 95% CI = 1.9-5.9 for highest tercile of exposure duration). Exposure-related
      risk estimates were reduced when age was introduced into the model. However, age
      and duration of exposure were highly correlated, (r = 0.68) suggesting a dilution
      of the exposure effect by age. CONCLUSIONS: There were significant dose related
      associations of disease, including emphysema, with coal dust exposure.

PMID- 16094612
TI  - Building informed consent for cholinesterase monitoring among pesticide handlers
      in Washington State.
AB  - BACKGROUND: Pesticide handlers in Washington State are predominantly Mexican and,
      therefore, require a culturally appropriate process of informed consent. In
      addition, members of this occupational group are vulnerable to coercion because
      of poverty, lack of insurance, inability to read, and employment status METHODS:
      To create a process of culturally competent informed consent for Washington
      State's cholinesterase monitoring program, we used focus groups to collect data
      about cultural beliefs, attitudes, knowledge, language, and traditions of Mexican
      American pesticide handlers. With this information, we developed a final consent
      form and evaluated it using a 10-item test-retest questionnaire in a sample of
      103 handlers. RESULTS: Using qualitative methods, we created English and Spanish
      consent forms that incorporated culturally defined risk information. Both the
      written and audiotape formats significantly improved comprehension; but, for
      subjects with less than 7 years of schooling, audiotapes in Spanish yielded
      significantly higher scores (mean comprehension score 7.0 vs. 6.1, t = - 2.2, P =
      0.03). CONCLUSIONS: Culturally competent informed consent for particularly
      vulnerable populations of non-native speakers of English is possible. It requires
      both knowledge of specific cultural elements and the application of appropriate
      technology.

PMID- 16094613
TI  - Multipoint linkage analysis for a very dense set of markers.
AB  - Multipoint linkage methods are powerful tools that are often employed as the
      first means to discover alleles affecting liability to diseases. With the advent
      of dense marker maps, linkage disequilibrium (LD) between markers is inevitable
      and it comes at the cost of bias and an increased rate of false-positive findings
      for linkage analyses that assume alleles of different markers are independent. I
      propose a "multipoint on subsets" method that avoids this issue by partitioning
      the markers into interlaced and non-overlapping subsets. Each subset is analyzed
      separately, their statistics are then averaged, and the resulting average is
      standardized by its estimated standard deviation. In addition to being robust to
      the challenges induced by dependent marker alleles, data simulated under linkage
      equilibrium show that the proposed method does not suffer any detectable loss of
      power when compared to traditional methods.

PMID- 16094614
TI  - Experimentally produced diploid-triploid mouse chimaeras develop up to adulthood.
AB  - Spontaneous diploid-triploid chimaeras occur sporadically in various mammalian
      species including man, but so far have never been produced experimentally. In
      order to get a deeper insight into the developmental consequences of this
      anomaly, we have developed two procedures that enabled for the first time to
      produce routinely diploid-triploid embryos, foetuses, and animals in the mouse.
      These procedures are: (1) aggregation of cleaving diploid embryos with triploid
      embryos produced by suppression of the second polar body in zygotes, and (2)
      fusion of a haploid karyoplast with one blastomere of the two-cell diploid
      embryos. The first procedure yielded 23 living and 6 dead postimplantation
      embryos and foetuses (age: 8th-19th day) out of which 22 were chimaeric. In
      addition, three chimaeric neonates reached adulthood. Two animals were fertile,
      and one--an overt chimaera--was an infertile male. The rate of postimplantation
      development of aggregation chimaeras was normal or only slightly retarded, and
      with one exception the foetuses were morphologically normal. Generally, the
      highest contribution of the 3n component in extra-embryonic structures was noted
      in the yolk sac, and usually it was higher than its contribution to the organs of
      the body. Chimaerism was most often noted in the liver, the heart, the intestine,
      and the lungs. Participation of triploid cells to all tissues studied, both in
      the body and in extra-embryonic structures, appeared to decrease slightly as
      development progressed. The second procedure yielded 10 foetuses and 6 adults.
      Three foetuses were chimaeric. Six fertile adults were probably non-chimaeras:
      the triploid component was absent in the coat and in the blood.

PMID- 16094615
TI  - Risk of breast cancer among enlisted Army women occupationally exposed to
      volatile organic compounds.
AB  - BACKGROUND: The military presents a unique opportunity to study the incidence of
      disease in a population with complete knowledge of person-time and occupation.
      Women in the Army are employed more frequently in non-traditional, industrial
      jobs such as auto mechanic and motor transport operators than in the general US
      population, increasing the probability of exposure to industrial chemicals. A
      cohort to investigate the risk of breast cancer among active duty Army women
      occupationally exposed to volatile organic chemicals (VOCs) was constructed.
      METHODS: Age-adjusted incidence rates for breast cancer were calculated for more
      than 270,000 enlisted women who served between 1980-1996. Twenty-one VOCs,
      described in previously published literature as having a potential risk of breast
      cancer, were identified in an Army industrial hygiene survey database. Job title
      histories were linked to workplace chemical evaluations conducted by Army
      industrial hygienists, which included a subjective exposure potential rating
      (high, medium, low, and none) for each VOC. Poisson regression analysis was used
      to evaluate the association between the exposure rating by job title and breast
      cancer. RESULTS: The incidence of breast cancer in the cohort was significantly
      elevated in women younger than 35 years of age, especially among black women,
      when compared to the age-specific rates in the general population. Women who
      worked in occupations with a moderate to high exposure potential to at least one
      VOC had a 48% increased risk (P < 0.05) of breast cancer while on active duty
      between 1980-1996 when compared to those women with low to no exposure potential.
      CONCLUSIONS: This study provides preliminary evidence that exposure to one or
      more of the study VOCs is associated with an increased risk of breast cancer.
      Further substance-specific, quantitative analyses are warranted.

PMID- 16094616
TI  - Job strain and autonomic indices of cardiovascular disease risk.
AB  - BACKGROUND: Despite the epidemiological evidence linking job strain to
      cardiovascular disease, more insight is needed into the etiologic mechanisms.
      This, in turn, would help to more precisely identify risk. METHODS: We measured
      Job Strain using the Job Content Questionnaire, 8/day diary reports, and
      nationally standardized occupational code linkage, as well as autonomic
      regulation utilizing heart rate variability including spectral-derived components
      and QT interval variability in 36 healthy mid-aged males with varying strain
      jobs. The subjects wore Holter-monitors for 48 hr; this included a work and rest
      day. RESULTS: Job strain (P = 0.02) and low decision latitude (P = 0.004) were
      associated with a reduction in cardiac vagal control (HFP) persisting throughout
      the 48 hr. Job strain was also associated with elevations in sympathetic control
      during working hours (P = 0.003). CONCLUSIONS: The disturbed cardiovascular
      regulatory pattern associated with job strain may help explain the increased risk
      of cardiovascular diseases linked with occupational exposure.

PMID- 16094617
TI  - Pesticide exposures in professional turf applicators, job titles, and tasks
      performed: implications of exposure measurement error for epidemiologic study
      design and interpretation of results.
AB  - BACKGROUND: Little information on the validity of job title and task
      classifications, for the prediction of pesticide use or exposure, is available.
      METHODS: Job titles and task classifications were evaluated in relation to the
      absorbed dose of herbicides in 98 professional turf applicators. Self-reported
      use over a 1-week period and other proxies of pesticide use were compared with
      employer records. RESULTS: Job titles and tasks performed explained (R(2)) 11%
      and 16% of the variation in dose, respectively. Individuals who sprayed
      pesticides only, had the highest average doses in the study followed by those
      spraying and mixing, and those mixing only. The use of 2,4-D products by
      individual workers over a work season was not related to standardized measures of
      the amount purchased or used at the company. CONCLUSIONS: These findings suggest
      that job titles and tasks performed are poor proxies of pesticide use and
      exposures in professional turf applicators.

PMID- 16094618
TI  - World Trade Center dyspnea: bronchiolitis obliterans with functional improvement:
      a case report.
AB  - BACKGROUND: Bronchiolitis obliterans is a severe, often progressive, lung disease
      characterized by cough, exertional dyspnea, and airflow obstruction. It has been
      ascribed to specific causes such as lung or bone marrow transplant, medications
      for rheumatoid disease, and most recently in association with exposure to
      environmental agents. METHOD: A 42-year-old, previously healthy New York City
      Highway Patrol officer who arrived at the World Trade Center (WTC), "ground
      zero," early on September 11, 2001 was evaluated. He has been followed for over 2
      years with serial chest radiographs, CT scans, and pulmonary function studies. He
      eventually underwent an open lung biopsy. RESULTS: His dyspnea started on
      September 12, 2001 and progressed despite aggressive therapy with inhaled
      bronchodilator as well as oral and inhaled corticosteroids. At no time did he
      have any radiographic evidence of pulmonary disease. His forced vital capacity
      (FVC) decreased from 5.32 L in October 2001 to 2.86 L in January 2003. He
      underwent an open lung biopsy because of the persistent exertional dyspnea
      coupled with the loss of over 2 L of lung volume. The pathological findings were
      chronic bronchiolitis with focal obliterative bronchiolitis and rare non
      necrotizing granuloma. Symptoms and pulmonary function improved after therapy
      with Azithromycin was added to his treatment. DISCUSSION: This process is
      believed to be secondary to his massive exposure to the cloud of dust that
      followed the collapse of the WTC. It is our conviction that many of those present
      at the WTC on September 11 who have persistent dyspnea and deterioration of
      pulmonary function may have a similar pathologic process despite absence of
      abnormalities on CT of the chest. CONCLUSION: In view of the many signs and
      symptoms seen in first responders we feel that these findings provide important
      information about the pathophysiology and treatment of progressive disease
      resulting from this exposure.

PMID- 16094619
TI  - A report on the health of asbestos, Quebec miners 1940.
AB  - BACKGROUND: Twenty years after the start-up of the Canadian asbestos industry,
      reports began to appear of respiratory disease and deaths in asbestos workers in
      England and in France. An inquiry from the UK in 1912 as to the health of Quebec
      miners was met by a denial of ill-health, but the loading of the premiums of
      asbestos workers in the 1930s indicated that, despite further reassuring health
      studies on Quebec miners, actuaries had data that gave cause for serious concern.
      METHODS: A report made to the Canadian asbestos industry by a company doctor in
      1940, reviewing the literature and presenting his health findings on some 500
      employees, was studied in the context of the published information available at
      the time, and of unpublished contemporaneous material subsequently obtained by
      legal discovery. RESULTS: The physician denied that the health and longevity of
      Quebec's miners and millers were adversely affected, and was dismissive of
      earlier reports of there being serious health risks associated with working with
      asbestos. CONCLUSIONS: The methodology employed in his health study was defective
      and his denial of the literature uninformed. The study was widely circulated, and
      while it may have boosted Canadian industry morale, it met with a sceptical
      response from British industry. In denying that conditions in Quebec's asbestos
      mines and mills disabled and killed workers, the author allied himself to fellow
      professionals loyal to Government and to industry.

PMID- 16094620
TI  - Neuronal migration is transiently delayed by prenatal exposure to intermittent
      hypoxia.
AB  - BACKGROUND: Neonatal neurodevelopment is influenced by a variety of external
      factors, although the mechanisms responsible are poorly understood. Prenatal
      hypoxia, from physiological or chemical sources, can have no discernible effect,
      or can result in a broad spectrum of abnormalities. METHODS: To mimic some of the
      maternal effects of smoking, we developed a model that investigates the effects
      of intermittent hypoxia (IH), with or without concurrent nicotine in timed
      pregnant Sprague-Dawley rats. RESULTS: We found no significant differences
      between litter sizes or birthweight of pups from any treatment group, but animals
      exposed to IH (with or without nicotine) showed long term diminished body
      weights. Animals subjected to IH consistently showed a transient delay in
      neuronal migration early in the postpartum period, which was amplified by
      concurrent nicotine administration. We observed increased c-Abl protein levels in
      animals from the IH treatment groups. Multiple proteins involved in the intricate
      control of neuronal migration were also altered in response to this treatment,
      primarily the downstream targets of c-Abl: Cdk5, p25, and the cytoskeletal
      elements neurofilament H and F-actin and catalase. Catalase activity and protein
      levels, already elevated in response to IH, were further amplified by
      simultaneous nicotine exposure. CONCLUSIONS: This new model provides a novel
      system for investigating the effects of low grade IH in the developing brain and
      suggests that concurrent nicotine further aggravates many of the deleterious
      effects of IH.

PMID- 16094621
TI  - Soluble MICA in malignant diseases.
AB  - The immunoreceptor NKG2D activates natural killer cells and costimulates CD8 T
      cells. The MHC class I-related MICA molecules are ligands of NKG2D and are
      expressed on malignant, but not on normal, cells. As NKG2D plays an important
      role in the immunosurveillance of tumors, studies suggest that release of MICA
      from cancer cells constitutes an immune escape mechanism that systemically
      impairs antitumor immunity. Here, we investigated the potential of soluble MICA
      (sMICA) as a marker in cancer. Analysis of sMICA in sera of 512 individuals
      revealed significantly (p < 0.0001) higher levels in patients with various
      malignancies (n = 296, median 161 pg/ml) than in healthy individuals (n = 62,
      median <30 pg/ml). Patients with benign diseases (n = 154, median 84 pg/ml)
      exhibited intermediate sMICA levels. In cancer patients, elevated sMICA levels
      correlated significantly with cancer stage and metastasis (p = 0.015 and p =
      0.007, respectively). While release of MICA is thought to impair tumor immunity,
      determination of sMICA levels may provide useful additional information in the
      diagnosis and staging of cancer.

PMID- 16094622
TI  - Comprehensive analysis of the p53 status in mucosal and cutaneous melanomas.
AB  - The abrogation of the function of the "gatekeeper of the genome", p53, is the
      most prevalent molecular alteration in solid human tumors. Regarding melanomas
      the involvement of p53 alterations is discussed controversially to date. In order
      to evaluate the status of p53 in detail, primary tumors and metastases of 63
      sporadic cutaneous (CM) and mucosal (MuM) melanomas were examined by
      immunohistochemistry and sequence analysis of the entire coding region of the p53
      transcript, i.e., exons 2 to 11. In addition, loss of heterozygosity (LOH) and
      loss of allele-specific transcription (LOT) were determined. Accumulation of the
      p53 protein occurred in most of the CM and MuM specimens (71% and 58%,
      respectively). In contrast, protein stabilizing p53 mutations were observed in
      14% of the CM and no mutation was found in MuM specimens. Two of the aberrations
      located outside the core domain. LOH was detected in 22% CM and 58% MuM, and LOT
      in 25% of the CM specimens. The genotype distribution at the polymorphic p53
      codon 72 in melanoma patients differed significantly from control subjects. The
      calculation of odds ratios (OR) and 95% confidence intervals (CI) indicated an
      increased risk for developing cutaneous melanomas in individuals carrying the Pro
      coding allele. Altogether, aberrant p53 expression appears to be a common event
      in both CM and MuM.

PMID- 16094623
TI  - Serum samples should not be used to assess circulating matrix metalloproteinase-9
      levels as a prognostic marker of disease.

PMID- 16094624
TI  - Preschool diet and adult risk of breast cancer.
AB  - Events before puberty may affect adult risk of breast cancer. We examined whether
      diet during preschool age may affect a woman's risk of breast cancer later in
      life. We conducted a case-control study including 582 women with breast cancer
      and 1,569 controls free of breast cancer selected from participants in the
      Nurses' Health Study and the Nurses' Health Study II. Information concerning
      childhood diet of the nurses at ages 3-5 years was obtained from the mothers of
      the participants with a 30-item food-frequency questionnaire. An increased risk
      of breast cancer was observed among woman who had frequently consumed French
      fries at preschool age. For one additional serving of French fries per week, the
      odds ratio (OR) for breast cancer adjusted for adult life breast cancer risk
      factors was 1.27 (95% confidence interval [CI] = 1.12-1.44). Consumption of whole
      milk was associated with a slightly decreased risk of breast cancer (covariate
      adjusted OR for every additional glass of milk per day = 0.90; 95% CI = 0.82
      0.99). Intake of none of the nutrients calculated was related to the risk of
      breast cancer risk in this study. These data suggest a possible association
      between diet before puberty and the subsequent risk of breast cancer.
      Differential recall of preschool diet by the mothers of cases and controls has to
      be considered as a possible explanation for the observed associations. Further
      studies are needed to evaluate whether the association between preschool diet and
      breast cancer is reproducible in prospective data not subject to recall bias.

PMID- 16094625
TI  - Synthesis of poly(Pro-Hyp-Gly)(n) by direct poly-condensation of (Pro-Hyp
      Gly)(n), where n=1, 5, and 10, and stability of the triple-helical structure.
AB  - Pro-Hyp-Gly is a characteristic amino acid sequence found in fibrous collagens,
      and (Pro-Hyp-Gly)(10), which has been widely used as a collagen-model peptide,
      forms a stable triple-helical structure. Here, we synthesized polypeptides
      consisting of the Pro-Hyp-Gly sequence by direct poly-condensation of (Pro-Hyp
      Gly)(n), where n=1, 5, and 10, using 1-hydroxybenzotriazole and 1-ethyl-3-(3
      dimethyl-aminopropyl)-carbodiimide hydrochloride in both phosphate buffer
      (pH=7.4) and dimethylsulfoxide (DMSO) solutions for 48 h at 20 degrees C. The
      reaction of (Pro-Hyp-Gly)(5) and (Pro-Hyp-Gly)(10) in DMSO successfully gave
      polypeptides with molecular weights over 10,000, whereas low molecular weight
      products were obtained by reaction in phosphate buffer (pH=7.4). In contrast, Pro
      Hyp-Gly at a concentration of 50 mg/mL in phosphate buffer (pH=7.4) gave
      polypeptides with molecular weights over 10,000. The Fourier transform infrared
      (FTIR) and (1)H nuclear magnetic resonance (NMR) spectra of poly(Pro-Hyp-Gly)(10)
      revealed that the polymerization of (Pro-Hyp-Gly)(10) described in this report
      had no side reactions. Each polypeptide obtained shows a collagen-like triple
      helical structure, and the triple-helical structures of poly(Pro-Hyp-Gly) and
      poly(Pro-Hyp-Gly)(10) were stable up to T=80 degrees C, which suggests that the
      high molecular weight promotes stability of the triple-helical structure, in
      addition to the high Hyp content. Furthermore, transmission electron microscopy
      (TEM) observations show that poly(Pro-Hyp-Gly)(10) aggregates to form nanofiber
      like structures about 10 nm in width, which suggests that a Pro-Hyp-Gly repeating
      sequence contains enough information for triple-helix formation, and for
      subsequent nanofiber-like structure formation.

PMID- 16094627
TI  - Parental lung cancer as predictor of cancer risks in offspring: clues about
      multiple routes of harmful influence?
AB  - The carcinogenic effects of active smoking have been demonstrated for many sites,
      but the effects of passive smoking and exposures during pregnancy and
      breastfeeding are less well documented. We examined whether 0-70-year-old
      offspring of parents with lung cancer are at a risk of cancer that cannot be
      explained by their smoking or familial risk. It was assumed that known target
      sites for tobacco carcinogenesis would be affected, if any. The nationwide
      Swedish Family-Cancer Database with cancers recorded from 1958 to 2002 was used
      to calculate age-specific standardized incidence ratios (SIRs). Among offspring
      of affected mothers, increased risks were observed for upper aerodigestive (SIR
      1.45), nasal (2.93), lung (1.71) and bladder (1.52) cancers and for kidney cancer
      (6.41) in one age group. The risk of bladder cancer was found in younger age
      groups than that of lung cancer. Cancers at many of these sites, but not the
      kidney or the bladder, were in excess in offspring of affected fathers. Nasal
      cancer was even increased when either parent was diagnosed with lung cancer; the
      highest risk was for nasal adenoid cystic carcinoma (7.73). The data suggest that
      passive smoking during childhood is associated with an increase risk of nasal
      cancer. For bladder and kidney cancers, a contribution by tobacco carcinogens is
      implicated through breastfeeding and in utero exposure.

PMID- 16094628
TI  - Body size and risk of renal cell carcinoma in the European Prospective
      Investigation into Cancer and Nutrition (EPIC).
AB  - Previous studies suggest that obesity is related to increased risk of renal cell
      carcinoma (RCC); however, only a few studies report on measures of central vs.
      peripheral adiposity. We examined the association between anthropometric
      measures, including waist and hip circumference and RCC risk among 348,550 men
      and women free of cancer at baseline from 8 countries of the European Prospective
      Investigation into Cancer and Nutrition (EPIC). During 6.0 years of follow-up we
      identified 287 incident cases of RCC. Relative risks were calculated using Cox
      regression, stratified by age and study center and adjusted for smoking status,
      education, alcohol consumption, physical activity, menopausal status, and hormone
      replacement therapy use. Among women, an increased risk of RCC was conferred by
      body weight (relative risk [RR] in highest vs. lowest quintile = 2.13; 95%
      confidence interval [CI] = 1.16-3.90; p-trend = 0.003), body mass index (BMI) (RR
      = 2.25; 95% CI = 1.14-4.44; p-trend = 0.009), and waist (RR = 1.67; 95% CI = 0.94
      2.98; p-trend = 0.003) and hip circumference (RR = 2.30; 95% CI = 1.22-4.34; p
      trend = 0.01); however, waist and hip circumference were no longer significant
      after controlling for body weight. Among men, hip circumference (RR = 0.44; 95%
      CI = 0.20-0.98; p-trend = 0.03) was related significantly to decreased RCC risk
      only after accounting for body weight. Height was not related significantly to
      RCC risk. Our findings suggest that obesity is related to increased risk of RCC
      irrespective of fat distribution among women, whereas low hip circumference is
      related to increased RCC risk among men. Our data give further credence to public
      health efforts aiming to reduce the prevalence of obesity to prevent RCC, in
      addition to other chronic diseases.

PMID- 16094629
TI  - Dramatic synergistic anticancer effect of clinically achievable doses of
      lovastatin and troglitazone.
AB  - Lovastatin (an HMG-CoA reductase inhibitor) and troglitazone (a PPAR-gamma
      agonist) have been intensively studied prospectively for their application in
      cancer treatment. However, clinical trials of lovastatin or troglitazone in
      cancer treatment resulted in only limited responses. To improve their efficacy,
      lovastatin and troglitazone have, respectively, been tried to combine with other
      anticancer agents with varied outcomes. In our study, we found a dramatic
      synergism between lovastatin and troglitazone in anticancer at clinically
      achievable concentrations. This synergism was found in far majority of cell lines
      tested including DBTRG 05 MG (glioblastoma) and CL1-0 (lung). This amazing
      synergism was accompanied by synergistic modulation of E2F-1 and p27(Kip1), which
      were reported to mediate the anticancer activities of lovastatin and
      troglitazone, respectively, and other cell cycle regulating proteins such as
      CDK2, cyclin A and RB phosphorylation status. With this dramatic combination
      effect of lovastatin and troglitazone, a promising regimen of cancer therapy may
      be materialized in the future.

PMID- 16094630
TI  - Al-Qaeda's operational evolution: behavioral and organizational perspectives.
AB  - Al-Qaeda is widely regarded by the military, law enforcement, diplomatic, and
      intelligence communities as being the foremost threat to U.S. national security
      and safety. The nature of this threat, however, has changed since al-Qaeda first
      emerged in the late 1980s. This article describes the emergence of a new form of
      transnational terrorism and details al-Qaeda's progression from being an
      organization to an ideological movement. Drawing on a theory of social movements,
      we analyze its trajectory and the levels of influence. We also offer a behavioral
      perspective in explaining how al-Qaeda has adapted as a learning organization
      with new leadership, tactics, and patterns of recruitment and training.

PMID- 16094631
TI  - Social psychology, terrorism, and identity: a preliminary re-examination of
      theory, culture, self, and society.
AB  - This article relies upon structural symbolic interactionism and five of its
      organizing concepts (i.e. symbols, the definition of the situation, roles,
      socialization and role-taking, and the self) to put forth a novel conceptual
      framework for understanding the terrorist identity. In order to demonstrate the
      practical utility of the framework, applications to various terrorist groups
      around the globe are incorporated into the analysis. Overall, both the
      theoretical and application work help reorient the academic and practitioner
      behavioral science communities to the importance of culture, self, and society
      when investigating one's membership in and identity through militant extremist
      organizations. Given the unique approach taken by this article, several
      provisional implications are delineated. In particular, future research on
      terrorism, strategies linked to counter-terrorism, legal and public policy
      reform, and the relevance of utilizing a sociologically animated social
      psychology in the assessment of other forms of criminal behavior are all very
      tentatively explored.

PMID- 16094632
TI  - Biodegradable membrane-covered stent from chitosan-based polymers.
AB  - Membrane-covered devices could help treat disease of the vasculature such as
      aneurysm, rupture, and fistulas. They are also investigated to reduce embolic
      complication associated with revascularization of saphenous vein graft. The aim
      of this study is to design a clinically applicable biodegradable membrane-covered
      stent based on the natural polysaccharide chitosan, which has been developed. The
      mechanical properties of the membrane is optimized through blending with
      polyethylene oxide (70:30% Wt CH:PEO). The membrane was able to sustain the
      mechanical deformation of the supporting self-expandable metallic stents during
      its deployment. The membrane was demonstrated to resist physiological transmural
      pressure (burst pressure resistance >500 mm Hg) and presented a high-water
      permeation resistance (1 mL/cm(2) min(-1) at 120 mmHg). The CH-PEO membrane
      showed a good hemocompatibility in an ex vivo assay. Heparin and hyaluronan
      surface complexation with the membrane further reduced platelet adhesion by 50.1
      and 63% (p = 0.05). The ability of the membrane-covered devices to be used as a
      drug reservoir was investigated using the nitric oxide donor sodium nitroprusside
      (SNP). SNP-loaded membranes displayed significantly reduced platelet adhesion.

PMID- 16094633
TI  - Zinc blocks gene expression of mitochondrial aconitase in human prostatic
      carcinoma cells.
AB  - Mitochondrial aconitase (mACON) contains a [4Fe-4S] cluster as the key enzyme for
      citrate oxidation in the human prostatic epithelial cell. Although there is
      accumulating evidence indicating that accumulation of high levels of zinc in
      prostate epithelial cells causes reduced efficiency of citrate oxidation, zinc
      regulation on the mACON is still not well understood. From in vitro studies, zinc
      chloride treatment has been developed using humic acid as the carrier (Zn-HA) in
      human prostatic carcinoma cells, PC-3. Zn-HA treatment (0.1-10 microM) restricts
      mACON enzymatic activity, which attenuates citrate utility and decreases
      intracellular ATP levels in PC-3 cells, whereas the effect is blocked by adding
      the zinc chelator, diethylenetriaminepentaacetic acid (DTPA). Immunoblot,
      ribonuclease-protection and transient gene-expression assays indicate that Zn-HA
      treatments inhibit mACON gene expression. Mutation of the putative metal response
      element (MRE) from CTCGCCTTCA to TGATCCTTCA abolishes Zn-HA inhibition of mACON
      promoter activity. Our results have demonstrated that zinc possesses a specific
      regulatory mechanism on the mACON gene, and a biologic function of the putative
      metal regulatory system in mACON gene transcription has been identified.

PMID- 16094634
TI  - Polymorphism of Xeroderma Pigmentosum group G and the risk of lung cancer and
      squamous cell carcinomas of the oropharynx, larynx and esophagus.
AB  - We investigated the effects of XPG His1104Asp polymorphism (rs17655) on the risk
      of lung cancer and squamous cell carcinomas of the oropharynx, larynx and
      esophagus (SCCOLE). This population-based case-control study involves 611 new
      cases of lung cancer, 601 new cases of oropharyngeal, laryngeal and esophageal
      cancers, and 1,040 cancer-free controls. The XPG polymorphism was assayed by PCR
      RFLP method for 497 lung cancer cases, 443 cases of oropharyngeal, laryngeal and
      esophageal cancers and 912 controls. Binary and polytomous unconditional logistic
      regression models were fitted to assess the main effects and the effect
      modifications between the polymorphism and environmental exposures. With the
      adjustment for potential confounders, the XPG Asp1104Asp genotype was inversely
      associated with lung cancer (odds ratio [OR] = 0.62, 95% confidence limits [CL] =
      0.38, 1.0) and SCCOLE (OR = 0.47, 95% CL = 0.27, 0.82), with the combined
      His1104His and His1104Asp genotypes as the referent. With subjects having
      genotype Asp1104Asp and no tobacco smoking exposure as the common referent, the
      ORs on lung cancer were 13 (95% CL = 4.4, 37) for heavy tobacco smoking (>20 pack
      years), 1.9 (95% CL = 0.78, 4.5) for having at least one copy of 1104His, and 23
      (95% CL = 9.5, 56) for the joint effect, respectively. Compared to non-smokers
      with the Asp1104Asp genotype, the adjusted OR on SCCOLE for heavy smokers (>20
      pack-years) having at least one copy of 1104His was 8.0 (95% CL = 2.7, 24).
      Similarly, compared to non-drinkers with the Asp1104Asp genotype, the adjusted OR
      on SCCOLE for heavy drinkers (> or =3 drinks/day) with at least one copy of
      1104His was 10 (95% CL = 2.7, 38). In conclusion, our study suggests that the XPG
      Asp1104Asp genotype may be associated with decreased susceptibility to lung
      cancer and SCCOLE.

PMID- 16094635
TI  - Src family kinase members have a common response to histone deacetylase
      inhibitors in human colon cancer cells.
AB  - Histone deacetylase inhibitors (HDIs) induce cell cycle arrest, differentiation
      and/or apoptosis in numerous cancer cell types and have shown promise in clinical
      trials. These agents are particularly novel, given their ability to selectively
      influence gene expression. Previously, we demonstrated that the HDIs butyrate and
      trichostatin A (TSA) directly repress c-Src proto-oncogene expression in many
      cancer cell lines. Activation and/or overexpression of c-Src have been frequently
      observed in numerous malignancies, especially of the colon. Therefore, our
      observation was particularly interesting since butyrate is a naturally abundant
      component of the large intestine and has been suggested to be a cancer-preventive
      agent. However, c-Src is not the only Src family kinase (SFK) member to be
      implicated in the development of human cancers, including those of the colon.
      Therefore, the relative expression levels of known SFKs were examined in a panel
      of human colon cancer cell lines. We found a surprisingly diverse expression
      pattern but noted that most cell lines expressed relatively high levels of at
      least 2 SFKs. When the effects of butyrate and TSA were examined in
      representative cell lines, the expression of all SFKs was repressed in a dose-
      and time-dependent manner. Further, detailed examination of Lck, Yes and Lyn
      demonstrated that this repression had a direct effect on transcription and was
      independent of new protein synthesis. These results mirror our earlier data
      obtained with c-Src and suggest that SFKs are a major target of HDIs and likely
      account in part for the anticancer effects of these promising new drugs.

PMID- 16094636
TI  - What is terrorism and can psychology do anything to prevent it?
AB  - Terrorism has a long history, which continues to unfold, and takes many forms.
      Notwithstanding these facts, there is no generally accepted definition of
      terrorism. I set forth the definitional issues that underlie the current debate
      about terrorism. By comparing terrorism with various forms of violence, I argue
      that it is plausible to construe terrorism as crime and, in support of this, I
      demonstrate why terrorism cannot be morally justified. Next, I cluster various
      immediate and long-term approaches intended to prevent terrorism, highlighting
      psychologically based strategies, such as behavioral profiling, teaching
      tolerance and citizenship, modifying media images of terrorism, and building
      peace. In order to understand and respond more effectively to 21st-century
      terrorism, I advocate adoption of a multidisciplinary, contextually sensitive
      approach.

PMID- 16094637
TI  - A reassessment of state-level covariates of militia groups.
AB  - This study investigated state-level variation in the number of right-wing militia
      groups. We built on prior quantitative examinations by more carefully
      operationalizing theoretical concepts and testing alternative hypotheses offered
      to account for the etiology of social movements generally and of militias
      specifically. Using negative binomial regression, we found that, consistent with
      previous research, states with higher levels of farm job loss had more militia
      groups. However, in contrast to prior studies, we did not find gun culture,
      hospitable political climate, female empowerment, or general economic deprivation
      to be associated with the number of militia groups. We also found no relationship
      between the number of militia groups and levels of fundamentalist religious
      culture and minority empowerment. Our study was the first to test the effects of
      social disorganization on the number of militias in a state, and we found the two
      to be positively and significantly associated. We situate our results in the
      theoretical and empirical literature and outline two challenges for future
      research. First, scholars must operationalize variables carefully since different
      measures of the same theoretical concept may result in diverging conclusions.
      Second, since one major factor (i.e., social disorganization) found in this study
      to be associated with the number of militia groups in a state was examined here
      for the first time, it is important for researchers to continue to investigate
      new hypotheses.

PMID- 16094638
TI  - The intelligence community and the war on terror: the role of behavioral science.
AB  - The United States intelligence community has been under intense scrutiny from
      both inside and outside in the aftermath of September 11. Post mortem assessments
      of intelligence breakdowns may judge the events as more predictable than was in
      fact the actual reality. In a troubled world, when threats to national security
      can materialize very quickly, the intelligence community must be able to
      effectively and swiftly develop and implement plans to prevent further terrorist
      attacks on the homeland. Numerous scenarios need to be considered for the
      management of crisis situations. Intelligence actions must make it more difficult
      for terrorists to strike at their targets. The war on terror must confront a new
      generation of enemies who threaten to attack the United States with weapons of
      mass destruction. This essay will focus on the role of behavioral science and how
      related reforms within the intelligence community could improve its capability to
      respond to a huge challenge.

PMID- 16094639
TI  - Liability of professional and volunteer mental health practitioners in the wake
      of disasters: a framework for further considerations.
AB  - Qualified immunity from civil liability exists for acts of disaster mental health
      (DMH) practitioners responding to disasters or acts of terrorism. This article
      reviews current legal regimens dictating civil liability for potentially wrongful
      acts of DMH professionals and volunteers responding to disasters. Criteria are
      proposed to inform determinations of civil liability for DMH workers in disaster
      response, given current legal parameters and established tort law in relevant
      areas. Specific considerations are examined that potentially implicate direct
      liability of DMH professionals and volunteers, and vicarious liability of DMH
      supervisors for actions of volunteer subordinates. The relevance of pre-event DMH
      planning and operationalization of the plan post-event is linked to
      considerations of liability. This article concludes with recommendations to
      minimize liability exposure for DMH workers in response efforts.

PMID- 16094640
TI  - Terrorism-related risk management for health care facilities.
AB  - Clinicians should have a basic understanding of the physical and financial risk
      to mental health facilities related to external threat, such as (but not
      necessarily limited to) terrorism. Patient care and accessibility to mental
      health services rest not only on clinical skills, but on a place to practice them
      and an organized system supported by staff, physical facilities and funding.
      Clinicians who have some familiarity with the non-clinical requirements for care
      are in a position to support non-clinical staff in preventing care from being
      interrupted by external threats or events such as terrorist activity, and/or
      serving at the interface of facility operations and direct clinical care. Readers
      should note that this article is an introduction to the topic and cannot address
      all local, state, and national standards for hospital safety, or insurance
      providers' individual facility requirements.

PMID- 16094642
TI  - Exact family-based association tests for biallelic data.
AB  - Family-based study designs have an important role in the search for association
      between disease phenotypes and genetic markers. Unlike traditional case-control
      methods, family-based tests use within-family data to avoid identification of
      spurious associations that may result from population admixture. Many family
      based association tests have been proposed to accommodate a variety of
      ascertainment schemes and patterns of missing data. In this report, we describe
      exact family-based association tests for biallelic data. Specifically, we discuss
      test of the null hypotheses "no linkage and no association" and "linkage, but no
      association". These tests, which are valid under various models for inheritance
      and patterns of missingness, utilize the procedure proposed by Rabinowitz and
      Laird [2000: Hum Hered 50:211-223] that provides a unified framework for family
      based association testing (FBAT). The conditioning approach implemented in FBAT
      makes an exact test conceptually straightforward, but computationally difficult
      since the minimum sufficient statistics upon which we condition do not have a
      conventional form. An exact test may be especially critical when accurate
      computation of the extreme area of the FBAT statistic is needed, such as when the
      study design necessitates multiple comparisons adjustments. We describe the exact
      approach as a useful alternative to the asymptotic test and show that the exact
      tests for biallelic data may be most useful for the recessive disease model.

PMID- 16094644
TI  - The new face of terrorism: socio-cultural foundations of contemporary terrorism.

PMID- 16094643
TI  - Prospective study on the expression of cancer testis genes and antibody responses
      in 100 consecutive patients with primary breast cancer.
AB  - To determine the expression of cancer testis (CT) genes and antibody responses in
      a nonselected population of patients with primary breast cancer, we investigated
      the composite expression of 11 CT genes by RT-PCR in fresh biopsies of 100
      consecutive cases of primary breast carcinoma and by immunohistology in selected
      RT-PCR-positive cases. Antibody responses against 7 CT antigens were analyzed
      using recombinant antigen expression on yeast surface. In 98 evaluable cases, SCP
      1 and SSX-4 were expressed most frequently (both 65%), followed by HOM-TES-85/CT
      8 (47%), GAGE (26%), SSX-1 (20%), NY-ESO-1 (13%), MAGE-3 (11%), SSX-2 (8%), CT-10
      (7%), MAGE-4 (4%) and CT-7 (1%). One CT gene was expressed by 90% of the cases;
      79% expressed > or =2, 48% > or =3, 29% > or =4, 12% > or =5, 6% > or =6, 3% > or
      =7, 2% > or =8 and one case coexpressed 9 antigens. Of 100 serum samples screened
      for CT antigen-specific antibodies, antibodies against NY-ESO-1 were detected in
      4 patients, against SCP-1 in 6 patients and against SSX-2 in 1 patient, while no
      antibodies were detected against MAGE-3, CT-7 and CT-10. Expression of CT genes
      or antibody responses was not correlated with clinical parameters (menopausal
      status, tumor size, nodal involvement, grading, histology and estrogen receptor
      status) or the demonstration of CT gene expression at the protein level, by
      immunohistology. Our results show that breast carcinomas are among the tumors
      with the most frequent expression of CT antigens, rendering many patients
      potential candidates for vaccine trials.

PMID- 16094645
TI  - A family-based mental health program of recovery from state terror in Kosova.
AB  - Family processes of communication, mutual support, and sustenance of cultural
      values can play vital roles in recovery from psychological and material damage in
      societies afflicted by terror. This is particularly the case when a campaign of
      terror has specifically targeted family life and its traditions, when the culture
      is one whose identity has been centered in its families, and when public mental
      health resources have been scarce. At the end of the 1999 war in Kosova, the
      Kosovar Family Professional Educational Collaborative (KFPEC) was initiated to
      counter mental health sequelae of war in Kosova. This initiative focused upon the
      recovery and strengthening of Kosovar families, rather than the psychiatric
      treatment of individuals for post-traumatic symptoms. Findings and outcomes from
      this project may usefully inform the design of other international public mental
      health initiatives.

PMID- 16094646
TI  - Degradation of maternal mRNA in mouse embryos: selective degradation of specific
      mRNAs after fertilization.
AB  - During oogenesis, mRNA is actively transcribed and accumulated in growing
      oocytes, but this transcription stops before the oocytes grow to their full size.
      The accumulated maternal mRNA is used for protein synthesis in the oocytes during
      meiotic maturation and even in the embryos to sustain development after
      fertilization. Therefore, the degradation of accumulated maternal mRNA starts
      during meiotic maturation, but its rate is slow. Nevertheless, some mRNA species
      should rapidly degrade after fertilization if they encode proteins that play a
      role in specific events during meiosis and are detrimental for development after
      fertilization. In this study, to identify the selective degradation of maternal
      transcripts after fertilization, we sought mRNAs that are degraded in the early
      hours after fertilization by constructing an oocyte cDNA library after
      subtracting the cDNA of embryos at the mid one-cell stage. H1oo, c-mos, tPA
      (tissue type plasminogen activator gene), and Gdf9 were identified as genes whose
      transcripts undergo rapid degradation after fertilization. RT-PCR analysis showed
      that none of these transcripts was expressed during pre-implantation development
      once they were eliminated, suggesting that the mRNA species that are required for
      oogenesis, but not for early pre-implantation development, are degraded rapidly
      after fertilization. Microinjection of chimeric mRNAs in which the coding and 3'
      untranslated regions (3'UTR) were exchanged between c-mos and hypoxanthine
      phosphoribosyltransferase mRNAs revealed that the 3'UTR plays a role in the rapid
      degradation that occurs after fertilization. Cytoplasmic polyadenylation elements
      (CPEs) was found near a poly(A) signal in the 3'UTR of all the mRNA species
      identified as rapidly degrading mRNA. The mechanism for the selective degradation
      is discussed, in relation to its biological significance.

PMID- 16094647
TI  - Utility of ultrasound stimulation for activation of pig oocytes matured in vitro.
AB  - The present study was carried out to examine the development of pig oocytes after
      exposing to ultrasound under various conditions. When oocytes were exposed to
      ultrasound in the sorbitol medium, the blastocyst formation rate was
      significantly (P < 0.01) higher than that of oocytes exposed in HEPES-TLP-PVA.
      Optison, an echo-contrast microbubble, prevented the development into blastocysts
      of oocytes exposed to ultrasound in the sorbitol medium (P < 0.01). The mean
      number of cells in the blastocysts developed from oocytes exposed to ultrasound
      with 10% duty cycle was significantly (P < 0.05) higher than that obtained by
      using ultrasound with 50% duty cycle. The blastocyst formation rate of oocytes
      exposed to ultrasound for 30 sec was significantly (P < 0.05) higher than that
      exposed for 10 sec. There were no significant differences in the rates of oocytes
      developed to the blastocyst stage and the mean numbers of cells in the
      blastocysts among different intensities of ultrasound. The pronuclear formation
      and second polar body extrusion rates of oocytes exposed to ultrasound did not
      differ from eclectically activated oocytes. Although there was no significant
      difference in the blastocyst formation rates between different activation
      methods, the mean number of cells in the blastocysts developed from oocytes
      activated by exposing to ultrasound was significantly (P < 0.05) higher than that
      obtained by applying electric pulses. The results of the present study showed
      that ultrasound stimulation can induce the nuclear activation and parthenogenetic
      development of pig oocytes matured in vitro.

PMID- 16094648
TI  - Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer
      susceptibility and genomic DNA hypomethylation in an at-risk Italian population.
AB  - We performed a case-control study to examine the relationship between MTHFR C677T
      gene polymorphism (MTHFR677C/T) and gastric cancer susceptibility in at-risk
      populations in central Italy. To explore genomic DNA hypomethylation as a
      potential etiologic mechanism, this phenomenon was evaluated in carriers of the
      MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype.
      Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used
      for MTHFR677C/T genotyping. Unconditional regression analysis with ORs and 95%
      CIs was used to investigate the association of the polymorphism with disease.
      Genomic DNA methylation status by an established enzymatic assay that measures
      the DNA accepting capacity of methyl groups (inversely related to endogenous
      methylation) was assessed in a random sample of 40 carriers of the wild-type
      MTHFR677C/C genotype and 40 carriers of the MTHFR677T/T genotype. The global
      allelic distribution was in Hardy-Weinberg equilibrium. The MTHFR677T allele was
      significantly associated with gastric cancer risk with an OR of 2.49 (95% CI 1.48
      4.20) in heterozygous MTHFR677C/T carriers and an OR of 2.85 (95% CI 1.52-5.35)
      in homozygous MTHFR677T/T carriers. This risk association was retained in
      subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation
      status in MTHFR677T/T carriers was significantly higher than in subjects with
      wild-type MTHF677C/C genotype (p = 0.012). In the studied population, MTHFR677T
      played the role of a moderate-penetrance gastric cancer susceptibility allele.
      Possession of the MTHFR677T/T genotype was significantly associated with genomic
      DNA hypomethylation. These findings deserve further investigation in the context
      of novel strategies for gastric cancer prevention.

PMID- 16094649
TI  - Identification of flat dysplastic aberrant crypt foci in the colon of
      azoxymethane-treated A/J mice.
AB  - The role of aberrant crypt foci (ACF) as preneoplastic lesions in colon
      carcinogenesis is not clear. In Min/+ mice and their wild-type littermates
      treated with azoxymethane (AOM), we previously identified a subgroup of flat ACF
      that seem more immediate precursors of tumors than the classical elevated ACF. In
      the present study, we identified a similar subgroup of flat ACF in AOM-treated
      A/J mice and compared them with nascent tumors and classical elevated ACF. At
      week 1 and 2 after birth, A/J mice were injected subcutaneously with AOM (10
      mg/kg bw/injection). At weeks 7-14, we examined the luminal surface of
      unsectioned colon preparations stained with methylene blue in the inverse light
      microscope. The lesions were also examined by histopathology and
      immunohistochemistry. Surface examination revealed flat ACF, classical elevated
      ACF and nascent tumors. Since flat ACF were not observed as elevated structures,
      their bright blue appearance and compressed pit pattern of crypt openings seen
      with transillumination were used as criteria for their identification. Flat ACF
      and nascent tumors displayed a uniform picture of severe dysplasia, compressed
      pit pattern, overexpression of cytoplasmic/nuclear beta-catenin and nuclear
      overexpression of cyclin D1. Apparently, flat ACF and tumors represented the same
      type of dysplastic lesions at different stages of crypt multiplication. In
      contrast, classical elevated ACF did not seem to be as clearly related to
      tumorigenesis. They infrequently (1/20) possessed severe dysplasia,
      overexpression of cytoplasmic/nuclear beta-catenin, or nuclear overexpression of
      cyclin D1, and they did not have compressed crypt openings. Furthermore, flat ACF
      grew significantly faster than classical elevated ACF. In conclusion, our data
      indicate a development from flat ACF to adenoma characterized by aberrant
      activation of the Wnt signaling pathway and fast crypt multiplication. Classical
      elevated ACF do not seem to be as closely related to tumorigenesis.

PMID- 16094650
TI  - Inhibitory effect of linoleic acid on transformation of IEC6 intestinal cells by
      in vitro azoxymethane treatment.
AB  - The effect of linoleic acid (LA) on growth and transformation of IEC6 intestinal
      cells was examined. IEC6 cells expressed mRNAs of 15-lipooxygenase (LOX15) and
      peroxisome proliferator-activated receptor (PPAR)gamma but not COX-2. Cell growth
      was suppressed by LA in a dose-dependent manner in IEC6 cells. Three-week
      treatment with LA provided IEC6 cells a quiescent state. LA-induced growth
      inhibition was abrogated by exposure to antisense S-oligodeoxynucleotides (S
      ODNs) for LOX15 and/or PPARgamma. In an in vitro carcinogenesis model, IEC6
      cells, which had confirmed CYP2E1 expression and activity, were continuously
      treated with AOM and/or LA for 40 weeks. DNA injury in AOM-treated cells was
      suppressed to the control level by concurrent LA treatment. Colony formation of
      AOM-treated cells in soft agar was suppressed by treatment with LA, which was
      reversed by exposure to antisense S-ODNs for LOX15 and/or PPARgamma. AOM-treated
      IEC6 cells formed s.c. tumors in 9 of 12 mice, whereas AOM+LA-treated cells
      formed no tumor. IEC6 cells showed no remarkable alteration of protein production
      by AOM treatment, whereas cells treated with AOM+LA showed decreased epidermal
      growth factor receptor (EGFR) and phospho-EGFR and increased BAX. These findings
      suggest that LA inhibited AOM-induced transformation of COX-2-negative IEC6
      cells, which was possibly mediated with PPARgamma ligands generated by LOX15 from
      LA.

PMID- 16094651
TI  - Angiostatin's molecular mechanism: aspects of specificity and regulation
      elucidated.
AB  - Tumor growth requires the development of new vessels that sprout from pre
      existing normal vessels in a process known as "angiogenesis" [Folkman (1971) N
      Engl J Med 285:1182-1186]. These new vessels arise from local capillaries,
      arteries, and veins in response to the release of soluble growth factors from the
      tumor mass, enabling these tumors to grow beyond the diffusion-limited size of
      approximately 2 mm diameter. Angiostatin, a naturally occurring inhibitor of
      angiogenesis, was discovered based on its ability to block tumor growth in vivo
      by inhibiting the formation of new tumor blood vessels [O'Reilly et al. (1994a)
      Cold Spring Harb Symp Quant Biol 59:471-482]. Angiostatin is a proteolytically
      derived internal fragment of plasminogen and may contain various members of the
      five plasminogen "kringle" domains, depending on the exact sites of proteolysis.
      Different forms of angiostatin have measurably different activities, suggesting
      that much remains to be elucidated about angiostatin biology. A number of groups
      have sought to identify the native cell surface binding site(s) for angiostatin,
      resulting in at least five different binding sites proposed for angiostatin on
      the surface of endothelial cells (EC). This review will consider the data
      supporting all of the various reported angiostatin binding sites and will focus
      particular attention on the angiostatin binding protein identified by our group:
      F(1)F(O) ATP synthase. There have been several developments in the quest to
      elucidate the mechanism of action of angiostatin and the regulation of its
      receptor. The purpose of this review is to describe the highlights of research on
      the mechanism of action of angiostatin, its' interaction with ATP synthase on the
      EC surface, modulators of its activity, and issues that should be explored in
      future research related to angiostatin and other anti-angiogenic agents.

PMID- 16094652
TI  - Estimation of peroneal and tibial afferent activity from a multichannel cuff
      placed on the sciatic nerve.
AB  - The afferent signals recorded with a multi-electrode cuff on the sciatic nerve
      were employed to investigate the possibility of extracting components ascending
      from the peroneal and tibial nerves. Two methods, an inverse regression model and
      principal component method, were studied. The parameters of inverse regression
      model, determined by data collected in semistatic conditions, were validated by
      data collected in dynamic conditions. The results showed that the regression
      model, which used only two channels of the sciatic recordings, was sufficient to
      separate the distal afferent components. The model, at the expense of requiring
      distal branch recordings for estimating model parameters, yielded better
      separation than the principal component method. In conclusion, peroneal and
      tibial afferent activity can be estimated from the sciatic nerve: the principal
      component method is suitable for applications focused on acquiring afferent
      information, whereas the inverse regression model is better for applications in
      which stimulations will be applied to the branches. The estimation technique
      provides a powerful tool for in vivo investigation of sensory information
      transmitted in a peripheral nerve and facilitates implementation of advanced
      functional neuromuscular stimulation systems.

PMID- 16094653
TI  - Predictors of noninvasive ventilation tolerance in patients with amyotrophic
      lateral sclerosis.
AB  - Noninvasive ventilation (NIV) appears to improve survival and quality of life in
      patients with amyotrophic lateral sclerosis (ALS), but little is known about
      predictors of NIV tolerance. NIV use was assessed and clinical predictors of
      tolerance were investigated, using predictive modeling, in ALS patients diagnosed
      and followed in our clinic until death over a 4-year time period. Patients were
      prescribed NIV based on current practice parameters when respiratory symptoms
      were present or forced vital capacity was less than 50%. We prescribed NIV in 52%
      (72) of patients. For those prescribed NIV, information regarding tolerance was
      available for 50 patients, with 72% (36) tolerant to its use. Tolerance was six
      times more likely in limb-onset than bulbar-onset ALS patients, with a trend
      toward reduced tolerance in those with lower forced vital capacity at NIV
      initiation. Age, gender, and duration of disease were not predictors of NIV
      tolerance. We conclude that a majority of ALS patients who are prescribed NIV can
      successfully become tolerant to its use.

PMID- 16094654
TI  - Myasthenia gravis and myasthenic syndrome: simulation of twitch strength with or
      without therapy.
AB  - To examine the quantitative relationship between indirectly evoked twitch and
      decreases in the number of either postsynaptic receptors or acetylcholine
      molecules released by a single stimulus, we studied these variables in a computer
      simulated model of neuromuscular transmission. Twitch strength decreased if the
      number of receptors decreased to below 30% of normal or the number of
      acetylcholine molecules released by a stimulus decreased to below 80%. Inhibition
      of acetylcholine hydrolysis to 50% restored twitch strength in the presence of a
      decreased number of receptors. However, twitch strength was more easily restored
      to normalcy by augmenting the release of acetylcholine, if the release was
      diminished by disease. The simulations mimic the clinically known therapeutic
      outcomes in certain disorders of neuromuscular transmission. These results
      provide useful quantitative insights into the relationship between acetylcholine
      receptors or the stimulus-induced release of acetylcholine and muscle function in
      myasthenia gravis or Lambert-Eaton myasthenic syndrome.

PMID- 16094655
TI  - Structural features of forming and developing blood capillaries of the enamel
      organ of rat molar tooth germs observed by light and electron microscopy.
AB  - The process of vascularization of the enamel organ, a unique epithelial
      structure, occurs when the tooth germ is fully developed, i.e., at the onset of
      dentinogenesis. Although the three-dimensional organization of the capillaries
      has been previously investigated, the structural features underlying the
      formation of the new capillaries remains poorly understood. Thus, in the hope of
      better understanding the mechanism of formation of the stellate reticulum
      capillaries, upper first molar tooth germs of newborn and 3-day-old rats were
      fixed in glutaraldehyde-formaldehyde and processed for light and electron
      microscopy. Our results showed that blood capillaries are initially in close
      proximity to the outer enamel epithelium. Between and intercalated with the
      capillaries are round/ovoid clusters of cells, some of which are vacuolated,
      closely apposed to the outer enamel epithelium. The outer enamel epithelium is
      not a continuous layer, but exhibits gaps between the cells. This suggests that
      the capillaries penetrate the enamel organ through these gaps, since no
      invagination of the epithelium was observed. The presence of a cluster of cells
      containing vacuoles suggests that vasculogenesis is taking place. Images showing
      loss of the basal lamina, proliferation of endothelial cells, presence of
      filopodia and lateral sprouting suggests that angiogenesis is also occurring.
      Thus, neoformation of capillaries of the molar enamel organ of rat seems to occur
      simultaneously by mechanisms of vasculogenesis and angiogenesis.

PMID- 16094656
TI  - Statins and polyneuropathy: setting the record straight.

PMID- 16094657
TI  - Osteology and skeletal development of Phyllomedusa vaillanti (Anura: Hylidae:
      Phyllomedusinae) and a comparison of this arboreal species with a terrestrial
      member of the genus.
AB  - Few descriptions of skeletal development and morphology exist for neobatrachians,
      despite their abundance and diversity. Herein, the adult morphologies of
      Phyllomedusa vaillanti and P. atelopoides are described and compared and the
      ontogeny of the larval skeleton of P. vaillanti is described and compared with
      those of Hyla lanciformis (the only hylid for which a detailed cranial and
      postcranial osteological ontogenesis has been described) and P. trinitatis (the
      only other member of this genus for which the larval skeleton has been
      described). These descriptions and comparisons are made on the basis of cleared
      and double-stained, dry skeletal, and alcohol-preserved specimens. In P.
      vaillanti, the first elements that ossify are the neural arches of the presacral
      vertebrae (Gosner Stage 34), followed by the parasphenoid, occipital condyles,
      exoccipitals, and prootics at Stage 38; many elements of the postcranial skeleton
      ossify contemporaneously with the first cranial elements. Major modifications of
      the chondrocranium begin at Stage 44. In adults, the skulls of P. vaillanti and
      P. atelopoides do not seem atypical of hylid frogs, and their elements are
      gracile and unornamented. Although P. atelopoides is a terrestrial species, the
      morphology of its hands and feet does not seem to differ dramatically from that
      of other phyllomedusines, which are arboreal; however, the relative lengths of
      the appendages and vertebral column are shorter and more robust than those of all
      other Phyllomedusa.

PMID- 16094658
TI  - Venlafaxine extended release versus conventional antidepressants in the remission
      of depressive disorders after previous antidepressant failure: ARGOS study.
AB  - Serotonin-norepinephrine reuptake inhibitors (SNRIs) may be used as an
      alternative treatment for depressed patients who do not tolerate or respond
      adequately to treatment with a conventional antidepressant. This randomized, open
      label, multicenter study compared the effectiveness of the SNRI venlafaxine
      extended release (VXR) with that of conventional antidepressants (CA) in patients
      who were referred to an outpatient psychiatric specialty care setting for
      treatment after failure to tolerate or respond to at least 4 weeks of treatment
      with a CA in a primary care setting. Patients with a Hamilton Depression Rating
      Scale (HAM-D17) score > or =17 were randomly assigned to treatment with an
      alternative CA or VXR. Remission was defined as a score < or =7 on the HAM-D17.
      Efficacy analyses were carried out on 3,097 patients from the intent-to-treat
      (ITT) population (1,632 VXR; 1,465 CA). The antidepressants prescribed most
      frequently in the CA group were paroxetine (21.3%), citalopram (20.1%),
      sertraline (19.1%), fluoxetine (17.0%), and mirtazapine (7.9%). After 24 weeks of
      treatment, the VXR group demonstrated a significantly higher remission rate than
      did the CA group (59.3% VXR; 51.5% CA; P<.0001; odds ratio: 1.37; 95% CI: 1.19
      1.58; P<.01). Despite the limitations of the open design, the results of this
      study suggest that venlafaxine extended release may be more effective than the
      conventional antidepressants used in this study when treating depressed patients
      who do not tolerate or respond adequately to treatment with a conventional
      antidepressant.

PMID- 16094659
TI  - Sleep paralysis among Cambodian refugees: association with PTSD diagnosis and
      severity.
AB  - Among Cambodian refugees attending a psychiatric clinic (n=100), 49% (49/100) had
      at least one episode of sleep paralysis (SP) in the previous 12 months. The
      annual and monthly SP prevalences were much higher in posttraumatic stress
      disorder (PTSD) than in non-PTSD patients. Among the PTSD patients, 65% (30/46)
      had monthly episodes of SP versus 14.85% (8/54) among non-PTSD patients (chi2[2,
      n=100]=26.78, P<.001). Moreover, patients with SP in the last month (n=30) versus
      those without SP had much higher PTSD severity scores. In the entire sample
      (n=100), the PTSD severity scores correlated significantly with the rate of SP in
      the last month. During SP, Cambodian refugees usually hallucinated an approaching
      figure (90%, 44/49). The rate of SP-associated and post-SP panic attacks was
      high, indicating the great distress caused by the phenomenon. SP seems to be a
      core aspect of the Cambodian refugee's response to trauma. When treating
      Cambodian refugees, and traumatized refugees in general, clinicians should assess
      for its presence.

PMID- 16094660
TI  - Coexposure to benzo[a]pyrene and UVA induces DNA damage: first proof of double
      strand breaks in a cell-free system.
AB  - DNA damage induced by solar ultraviolet (UV) radiation plays an important role in
      the induction of skin cancer. Although UVA constitutes the majority of solar UV
      radiation, it is less damaging to DNA than UVB. The DNA damage produced by UVA
      radiation, however, can be augmented in the presence of a photosensitizer. We
      previously used benzo[a]pyrene (BaP), an environmental carcinogenic polycyclic
      aromatic hydrocarbon, as an exogenous photosensitizer, and demonstrated that
      combined exposure to BaP and UVA resulted in DNA double-strand breaks (DSBs) in
      cultured Chinese hamster ovary (CHO-K1) cells. In this study, we investigated
      whether coexposure to BaP and UVA induces DSBs in a cell-free system and whether
      reactive oxygen species (ROS) were involved in the generation of the DSBs. DSBs
      were induced by the coexposure both in the cell-free system (in vitro) and in CHO
      K1 cells (in vivo), but not by treatment with BaP or UVA alone. DSB induction in
      vitro required higher doses of UVA and BaP than were required in vivo, suggesting
      that the mechanism of DSB induction differed. A similar difference in efficiency
      also was observed in the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8
      oxodG) by coexposure to BaP and UVA in vitro and in vivo. A singlet oxygen
      ((1)O2) scavenger (NaN3) effectively inhibited the production of DSBs and 8
      oxodG, suggesting that (1)O2 is a principal ROS generated by BaP and UVA both in
      vitro and in vivo. Furthermore, repair-deficient xrs-5 cells were more sensitive
      to coexposure with BaP and UVA than were CHO-K1 cells, but the two cell lines
      were equally sensitive to the combined treatment in the presence of NaN3. This
      result suggested that the cell death produced by coexposure to BaP and UVA was at
      least partly due to the DSBs generated by (1)O2. Our findings indicate that
      coexposure to BaP and UVA effectively induced DNA damage, especially DSBs, which
      results in phototoxicity and possibly photocarcinogenesis.

PMID- 16094661
TI  - 3,4-Epoxy-1-butene, a reactive metabolite of 1,3-butadiene, induces somatic
      mutations in Xpc-null mice.
AB  - Xpc-null (Xpc-/-) mice, deficient in the global genome repair subpathway of
      nucleotide excision repair (NER-GGR), were exposed by intraperitoneal (i.p.)
      injection to a 300 mg/kg mutagenic dose of 3,4-epoxy-1-butene (EB), to
      investigate NER's potential role in repairing butadiene (BD) epoxide DNA lesions.
      Mutagenic sensitivity was assessed using the Hprt assay. Xpc-/- mice were
      significantly more sensitive to EB exposure, exhibiting an average 2.8-fold
      increase in Hprt mutant frequency (MF) relative to those of exposed Xpc+/+ (wild
      type) mice. As a positive control for NER-GGR, additional mice were exposed by
      i.p. injection to a 150 mg/kg mutagenic dose of benzo[a]pyrene (B[a]P). The Xpc-/
      mice had MFs 2.9-fold higher than those of exposed Xpc+/+ mice. These results
      suggest that NER-GGR plays a role in recognizing and repairing some of the DNA
      adducts formed following in vivo exposure to EB. Additional research is needed to
      examine the response of Xpc-/- mice, as well as other NER-deficient strains, to
      inhaled BD. Furthermore, it is likely that alternative DNA repair pathways also
      are involved in restoring genomic integrity compromised by BD-epoxide DNA damage.
      Collaborative studies are currently underway to address these critical issues.

PMID- 16094662
TI  - Results of a naturalistic longitudinal study of benzodiazepine and SSRI use in
      the treatment of generalized anxiety disorder and social phobia.
AB  - The past decade has brought major new developments in the psychopharmacologic
      management of generalized anxiety disorder and social phobia. We examined
      medication-prescribing patterns for the treatment of these anxiety disorders for
      12 years to assess changes in patients' anti-anxiety psychotropic medication
      usage during that period of evolving practice guidelines. We examined
      psychotropic medication use in 305 patients with generalized anxiety disorder and
      232 with social phobia enrolled in the Harvard/Brown Anxiety Disorders Research
      Project (HARP), a prospective, longitudinal study of anxiety disorders.
      Psychotropic treatment patterns seem to have remained relatively stable over 12
      years with benzodiazepines the medications most commonly used for both
      generalized anxiety disorder and social phobia. Comparatively, selective
      serotonin reuptake inhibitor (SSRI) and venlafaxine usage as stand-alone
      medications for these disorders remained low throughout the follow-up period. At
      the 12-year follow-up, 24% of patients with generalized anxiety disorder and 30%
      of patients with social phobia were utilizing neither an SSRI/selective
      norepinephrine reuptake inhibitor (SNRI) nor a benzodiazepine. Treatment
      recommendations for use of SSRIs and venlafaxine in the management of generalized
      anxiety disorder and social phobia initially promulgated in 1998 had a modest
      impact on changes in psychopharmacologic practice 4-5 years later. Difficulties
      in the implementation of treatment guidelines are discussed.

PMID- 16094663
TI  - Venlafaxine in the treatment of depressive and vasomotor symptoms in women with
      perimenopausal depression.
AB  - Perimenopause is often marked by vasomotor symptoms and dysphoria. Antidepressant
      studies have demonstrated decreased frequency and severity of hot flashes in
      breast cancer survivors and menopausal women. We hypothesized that venlafaxine
      would relieve both depressive and vasomotor symptoms in depressed perimenopausal
      women. Sixteen women fulfilling clinical criteria for climacteric phase and
      Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for a
      depressive episode were enrolled in an open-label 8-week trial of extended
      release venlafaxine. Depressive and climacteric symptoms were monitored using the
      Hamilton Rating Scales for Depression (Ham-D) and Anxiety (Ham-A), Clinical
      Global Impression (CGI) scale, and Greene Climacteric Scale (GCS). Serum
      follicular stimulating hormone (FSH) and estradiol concentrations were monitored.
      Significant decreases in Ham-D and Ham-A scores and the GCS psychiatric subscale
      were seen after 2 weeks of treatment. In an intention-to-treat analysis, 81% of
      the subjects demonstrated a therapeutic antidepressant response (>50% decline in
      Ham-D score) and 75% achieved clinical remission (Ham-D score < or =7) after 8
      weeks of venlafaxine therapy (75-225 mg/day). Total GCS scores declined 60%, and
      GCS vasomotor subscores decreased among those with vasomotor symptoms at
      baseline. These data suggest that venlafaxine treatment improves overall well
      being, reduces depressive symptoms, and may diminish baseline vasomotor symptoms
      in depressed perimenopausal women. Further studies are warranted to investigate
      the utility of venlafaxine in perimenopausal depression.

PMID- 16094664
TI  - Hydrolytic degradation behavior of biodegradable polyetheresteramide-based
      polyurethane copolymers.
AB  - In this article, a new kind of biodegradable polyetheresteramide-based
      polyurethane (PEEA-U) copolymers were prepared by the melt polycondensation
      method from epsilon-caprolactone, 6-aminocaproic acid, poly(ethylene glycol), and
      toluene diisocyanate. The water absorption of PEEA-U was affected strongly by the
      reaction time and the content of chain extender; and the hydrolytic degradation
      behavior of the copolymers was mainly determined by the reaction time, chain
      extender content, and the pH value of the degradation medium. Also, DSC, (1)H
      NMR, and inherent viscosity were used to characterize the degradation behavior of
      the copolymers.

PMID- 16094665
TI  - In vivo evaluation of a porous hydroxyapatite/poly-DL-lactide composite for use
      as a bone substitute.
AB  - We investigated the biocompatibility, osteoconductivity, and biodegradability of
      a porous composite of hydroxyapatite (HA) and poly-DL-lactide (PDLLA) implanted
      into rabbit femoral condyles and compared it with porous HA. Six weeks after
      implantation, the HA/PDLLA was covered with bone and contacted the bone directly.
      The amount of newly formed bone in the pores was similar in both materials during
      the examined period. The newly formed bone in the HA/PDLLA tended to increase
      over 26 weeks, but that in the HA did not show a significant increase after 12
      weeks. By 26 weeks, remodeling of the newly formed bone in the pores was seen and
      bone marrow tissue was found in the pores of the HA/PDLLA. The porous HA/PDLLA
      was resorbed much faster than the porous HA. Porous HA/PDLLA was resorbed
      continuously through bone formation and remodeling. Conversely, porous HA was
      scarcely resorbed throughout the period. HA/PDLLA is thought to be degraded
      almost completely after about 1 year, and in this study, porous HA/PDLLA showed
      excellent osteoconductivity and faster resorption than HA. Therefore, HA/PDLLA
      might be a desirable material for bone substitutes.

PMID- 16094666
TI  - Long-term outcome after radiotherapy alone for lymphocyte-predominant Hodgkin
      lymphoma: a retrospective multicenter study of the Australasian Radiation
      Oncology Lymphoma Group.
AB  - BACKGROUND: The curative potential of radiotherapy (RT) alone as initial
      treatment for patients with Stage I-II lymphocyte-predominant Hodgkin lymphoma
      (LPHL) has not been defined well. METHODS: Two hundred two patients who were
      treated between 1969 and 1995 were evaluated in a retrospective, multicenter
      study. RESULTS: Patient characteristics were as follows: The median age was 31
      years, 75% of patients were male, 80% of patients had Ann Arbor Stage I disease,
      1% of patients had bulky disease, 3% of patients had B symptoms, 1% of patients
      had extranodal involvement, and 80% of patients had supradiaphragmatic disease.
      The RT fields were a full mantle field in 52% of patients, less than a full
      mantle field in 24% of patients, an inverted-Y field in 17% of patients, less
      than an inverted-Y field in 3% of patients, and total lymph node irradiation in
      3% of patients. The median dose was 36 Gray. The median follow-up was 15 years.
      The overall survival (OS) rate at 15 years was 83%, and freedom from progression
      (FFP) was observed in 82% of patients, including 84% of patients with Stage I
      disease and 73% of patients with Stage II disease. No recurrent LPHL and only 1
      patient with non-Hodgkin lymphoma (NHL) were reported after 15 years. Adverse
      prognostic factors that were identified on multifactor analysis were as follows:
      for OS, age 45 years or older (P < 0.0005), the presence of B symptoms (P =
      0.002), increasing number of sites (P = 0.015); for FFP, increasing number of
      sites (P = 0.002). No significant difference was found in FFP in a comparison of
      patients who received elective mediastinal RT with patients who did not receive
      mediastinal RT (P = 0.11). Causes of death at 15 years were LPHL in 3% of
      patients, NHL in 2% of patients, in-field malignancy in 2% of patients, in-field
      cardiac/respiratory in 4% of patients, and other in 6% of patients. CONCLUSIONS:
      The current data suggested that RT potentially may be curative for patients with
      Stage I-II LPHL and raise the possibility that limited-field RT may be used
      without loss of treatment efficacy. Involved-field RT warrants further
      investigation for patients with early-stage LPHL.

PMID- 16094668
TI  - Positioning, displacement, and localization of cells using ultrasonic forces.
AB  - This paper presents a method and a device to position and displace cells. The
      cells are suspended in a fluid layer trapped between the device and an arbitrary
      surface such as an object slide or a wafer. The device vibrates at ultrasonic
      frequencies causing a pressure field in the fluid layer. This pressure field
      results in a force-field capable of positioning cells. Depending on the way in
      which the device is excited a 2-D or 3-D force-field can be generated,
      positioning the cells in lines or points respectively. Furthermore, it is
      possible to subsequently displace the cells with micrometer accuracy. This has
      been demonstrated using HL60 and MCF10A cells, and can be achieved without
      causing damage to the cells.

PMID- 16094669
TI  - Separation of polyunsaturated fatty acids by selective inclusion in guanidinium
      1,5-naphthalenedisulfonate-2-methoxyethanol host networks.
AB  - Hydrogen-bonded networks composed of guanidinium (G) and 1,5
      naphthalenedisulfonate (NDS) have been developed for the selective inclusion and
      separation of fatty acid esters based on their degree of unsaturation. Porous
      crystalline networks have been synthesized and include fatty acid esters during
      crystallization from both methanol and 2-methoxyethanol. Crystalline networks
      formed in methanol are selective for the inclusion of saturates in preference to
      polyunsaturated fatty acid methyl esters, but their applicability is limited by
      the competing inclusion of the solvent methanol. In 2-methoxyethanol, a three
      component host structure is formed that provides 4.1 x 4.7 A2 pores which are
      also selective for saturated fatty acid ester inclusion. These networks do not
      suffer from the competing inclusion of the solvent 2-methoxyethanol as is the
      case with methanol, and thus complete removal of initial saturated fatty acid 2
      methoxyethyl esters is possible. Binary selectivity experiments on mixtures of
      the 2-methoxyethyl esters of saturated stearic acid and the omega-3 fatty acid
      alpha-linolenic acid reveal that this three-component network structure provides
      nearly complete resolution of these two guests in the crystal and filtrate
      fractions. Separation of the 2-methoxyethyl esters of alpha-linolenic acid from
      the monounsaturated oleic acid is also possible, although with decreased
      efficiency in comparison to removal of the saturated fatty acid ester.

PMID- 16094667
TI  - Infants with Bochdalek diaphragmatic hernia: sibling precurrence and monozygotic
      twin discordance in a hospital-based malformation surveillance program.
AB  - Congenital diaphragmatic hernia (CDH) is a common and often devastating birth
      defect. In order to learn more about possible genetic causes, we reviewed and
      classified 203 cases of the Bochdalek hernia type identified through the Brigham
      and Women's Hospital (BWH) Active Malformation Surveillance Program over a 28
      year period. Phenotypically, 55% of the cases had isolated CDH, and 45% had
      complex CDH defined as CDH in association with additional major malformations or
      as part of a syndrome. When classified according to likely etiology, 17% had a
      Recognized Genetic etiology for their CDH, while the remaining 83% had No
      Apparent Genetic etiology. Detailed analysis using this largest cohort of
      consecutively collected cases of CDH showed low precurrence among siblings.
      Additionally, there was no concordance for CDH among five monozygotic twin pairs.
      These findings, in conjunction with previous reports of de novo dominant
      mutations in patients with CDH, suggest that new mutations may be an important
      mechanism responsible for CDH. The twin data also raise the possibility that
      epigenetic abnormalities contribute to the development of CDH.

PMID- 16094670
TI  - Neurogenesis and neuronal communication on micropatterned neurochips.
AB  - Neural networks are formed by accurate connectivity of neurons and glial cells in
      the brain. These networks employ a three-dimensional bio-surface that both
      assigns precise coordinates to cells during development and facilitates their
      connectivity and functionality throughout life. Using specific topographic and
      chemical features, we have taken steps towards the development of
      poly(dimethylsiloxane; PDMS) neurochips that can be used to generate and study
      synthetic neural networks. These neurochips have micropatterned structures that
      permit adequate cell positioning and support cell survival. Within days of
      plating, cells differentiate into neurons displaying excitability and
      communication, as evidenced by intracellular calcium oscillations and action
      potentials. The structural and functional capacities of such simple neural
      networks open up new opportunities to study synaptic communication and
      plasticity.

PMID- 16094671
TI  - Diversification of CDK11 transcripts during chicken testis development and
      regression.
AB  - CDK11 (cyclin-dependent kinase 11, formerly known as PITSLRE) is a
      serine/threonine kinase that associates with the cyclin L2 regulatory partner.
      CDK11 catalytic activity has been associated with apoptosis, transcription, and
      RNA processing. Here, we identify novel chicken testis CDK11 transcripts that
      differ in their 5'UTR, 3'UTR, splicing of the exon 6, and polyadenylation. We
      have also characterized the differential expression of CDK11 in somatic tissues,
      during testis development and upon testicular regression by diethylstilbestrol
      (DES) treatment. The heterogeneity of CDK11 transcripts presented in this study
      suggests new possibilities for post-transcriptional regulation.

PMID- 16094672
TI  - Characterization of pig vasa homolog gene and specific expression in germ cell
      lineage.
AB  - The vasa gene is known to be an important factor for germ cell development in
      both invertebrates and vertebrates. In the present study, we cloned the porcine
      vasa homolog (Pvh, 2,172 bps) and investigated its expression at mRNA and protein
      levels. The isolated cDNA had deduced 724 amino acid residues with significant
      homology to mouse (85%) and human (91%) vasa. In adult tissues, Pvh transcript
      was restricted to the ovary and testis, and was undetectable in somatic tissues.
      During preimplantation embryo development, Pvh was transcribed in oocytes and
      fertilized 2-cell embryos, but not in other preimplantation embryos. In fetal
      stage, the transcript of Pvh gene was expressed in all fetal stage, except in day
      17-18. Immunohistochemical analysis of fetal and adult gonad revealed that the
      Pvh protein was localized in oocytes and spermatocytes, consistent with mRNA
      expression. Interestingly, Pvh protein was also observed in proliferating
      primordial germ cells (PGCs) and freshly isolated PGCs, but not in embryonic germ
      cells. Our results suggest that Pvh gene can be a useful marker for germ cell
      development in pigs.

PMID- 16094673
TI  - Missense mutations in N-acetylglucosamine-1-phosphotransferase alpha/beta subunit
      gene in a patient with mucolipidosis III and a mild clinical phenotype.
AB  - Mucolipidosis type III (ML III, pseudo-Hurler polydystrophy), an autosomal
      recessive inherited disorder of lysosomal enzyme targeting is due to a defective
      N-acetylglucosamine 1-phosphotransferase (phosphotransferase) activity and leads
      to the impaired formation of mannose 6-phosphate markers in soluble lysosomal
      enzymes followed by their increased excretion into the serum. Mutations in the
      phosphotransferase gamma subunit gene (GNPTAG) have been reported to be
      responsible for ML III. Here we report on a 14-year-old adolescent with a mild
      clinical phenotype of ML III. He presented with progressive joint stiffness and
      swelling. Urinary oligosaccharide and mucopolysaccharide excretion was normal.
      Lysosomal enzyme activities were significantly elevated in the serum and
      decreased in cultured fibroblasts. Impaired trafficking of the lysosomal protease
      cathepsin D (CtsD) was confirmed by metabolic labeling of the patient's
      fibroblasts. Neither mutations in the GNPTAG gene nor alterations in the GNPTAG
      mRNA level were detected whereas the steady state concentration of the 97 kDa
      GNPTAG dimer was reduced. Most importantly, the patient is homozygous for a
      pathogenic nucleotide substitution and a polymorphism in the phosphotransferase
      alpha/beta subunit gene (GNPTA). The data indicate that defects in genes other
      than GNPTAG can be linked to ML III contributing to the variability of the
      phenotype.

PMID- 16094674
TI  - A new case of 2q duplication supports either a locus for orofacial clefting
      between markers D2S1897 and D2S2023 or a locus for cleft palate only on
      chromosome 2q13-q21.
AB  - We report on a pure duplication of the proximal chromosome 2q in a 6.5-year-old
      boy with V-shaped midline cleft palate and bifid uvula, posteriorly located
      tongue, and micrognathia (Pierre Robin sequence), celiac disease, failure to
      thrive, and developmental delay. Cytogenetic and FISH analysis indicated a
      duplication of chromosome 2q13-q22. In general, pure proximal duplication or
      triplication of 2q is rare. The clinical features and chromosomal breakpoints of
      the 10 previously reported patients varied, and no common phenotype or proximal
      duplication/triplication 2q syndrome could be defined to date. However, based on
      four previous patients with different orofacial clefts and our case, a locus for
      orofacial clefting may be located at proximal 2q. The duplication/triplication
      comprised chromosome 2q13 in all five affected individuals including our patient.
      Our patient and three previous cases (two with cleft palate only (CPO) and one
      with cleft lip/palate (CL/P)) showed a cytogenetic breakpoint at 2q13, which
      could support the presence of a critical dominant gene disrupted by a common
      breakpoint, however, the fifth case with CPO showed different breakpoints,
      advocating against the disruption of a critical dominant gene and supporting that
      the overexpression of a gene(s) on chromosome 2q13-q21 may cause cleft palate
      only (CPO) and Pierre Robin sequence. Hence, our findings support either the
      presence of one locus for orofacial clefting (CL/P, CPO, and Pierre Robin
      sequence) between markers D2S1897 (chromosome 2q12.2) and D2S2023 (chromosome
      2q14.2), or alternatively the presence of a locus for CPO and Pierre Robin
      sequence on chromosome 2q13-q21.

PMID- 16094675
TI  - A mouse gene encoding a novel member of the WD family of proteins is highly
      conserved and predominantly expressed in the testis (Wdr13).
AB  - Wdr13, a novel member of the WD family of proteins and the mouse homolog of WDR13
      is localized to the locus XA1.1 and is predominantly expressed in the testis. The
      expression begins at the early stages of gonadal development and is maintained
      throughout the adult life with a predominant expression in the germ cells of
      adult testis. RNA in situ hybridization on the testis and brain sections
      indicated a cytoplasmic expression of the transcript. The alternatively spliced
      transcripts of the gene are generated by different methods and showed a
      differential pattern of expression, suggesting functional diversity. The
      expression of the gene in the unfertilized egg and in the neural stem cells
      indicated the functional significance of the gene from the early stages of
      development. The nuclear localization of the mouse WDR13 protein suggested a
      regulatory function. Evolutionary analysis of the gene indicated an extensive
      functional conservation across diverse species. Comparison of the genomic
      organization of the different homologs revealed a varied organization in the
      invertebrate homolog and the retention of the functionally significant introns in
      the same.

PMID- 16094676
TI  - Pharmacokinetics and pharmacodynamics of intravenous torasemide in diabetic rats
      induced by alloxan or streptozotocin.
AB  - The pharmacokinetic and pharmacodynamic parameters of torasemide were compared
      after intravenous administration at a dose of 2 mg/kg to diabetic rats induced by
      alloxan (DMIA) or streptozotocin (DMIS), and their respective control rats. It
      was reported that torasemide was mainly metabolized via CYP2C11 in rats and the
      expression and mRNA level of CYP2C11 decreased in DMIA and DMIS rats. Hence, it
      could be expected that the time-averaged nonrenal clearance (Cl(nr)) of
      torasemide could be slower in the diabetic rats. As expected, the Cl(nr) values
      were significantly slower in DMIA (0.983 versus 1.35 ml/min/kg) and DMIS (0.998
      versus 1.36 ml/min/kg) rats. However, the time-averaged renal clearance (Cl(r))
      values of torasemide were significantly faster in DMIA (0.164 versus 0.0846
      ml/min/kg) and DMIS (0.205 versus 0.0967 ml/min/kg) rats due to urine flow rate
      dependent timed-interval Cl(r) of torasemide in rats. The comparable time
      averaged total body clearance (Cl) values between the diabetic and control rats
      were due to partially compensated Cl(r) in the diabetic rats. The 8 h urine
      output and diuretic efficiency increased significantly in the diabetic rats due
      to significantly greater 8 h urinary excretion of unchanged torasemide and at
      least partly due to an increase in urine output in diabetes per se (without
      administration of any drugs).

PMID- 16094677
TI  - A newly described thoracic vascular malformation in fetuses with Down syndrome.
AB  - OBJECTIVES: To report the association between thoracic vascular malformations
      observed in the first trimester of pregnancy and Down syndrome. METHODS: The
      clinical features were reviewed of seven fetuses undergoing chorionic villus
      sampling (CVS) for increased nuchal translucency (NT) thickness, in which color
      Doppler ultrasonography revealed a vascular malformation in the fetal thorax.
      RESULTS: The crown-rump length of the fetuses ranged from 58 to 78 mm and NT
      measurements ranged from 2.9 to 10.0 mm. Color Doppler allowed the identification
      of a highly vascular structure in the posterolateral portion of the fetal thorax,
      in proximity to the costovertebral angle, at the level of a four-chamber view of
      the heart. The lesions had a globular shape and were 4-6 mm in diameter,
      occupying almost one third of the hemithorax. Down syndrome was diagnosed in five
      out of the seven cases. In the only affected case that underwent postmortem
      examination, a hemangioma of the chest wall was demonstrated. In the two fetuses
      with normal karyotype, the lesion disappeared by mid-gestation. CONCLUSION: We
      report an association between the prenatal Doppler finding of a vascular tumor in
      the fetal chest and Down syndrome.

PMID- 16094678
TI  - Oxidative electrochemical switching in dithienylcyclopentenes, part 1: effect of
      electronic perturbation on the efficiency and direction of molecular switching.
AB  - The electro- and spectroelectrochemical properties of dithienylhexahydro- and
      dithienyhexafluorocyclopentenes are reported. The large effect of variation in
      the central cyclopentene moieties on the redox properties of the
      dithienylcyclopentenes is in striking contrast to the minor effect on their
      photochemical properties. The electronic properties of the oxidised compounds in
      the +1 and +2 oxidation state are reported, and the possibility of
      electrochemical cyclisation and cycloreversion were explored by UV/Vis
      spectroelectrochemistry. The efficiency of electrochemical switching is found to
      be dependent both on the central cyclopentene unit and on the nature of the
      substituents at C5 of the thienyl rings. For the hexahydrocyclopentene-based
      compounds oxidative ring closure of the ring-open form is observed, while for the
      hexafluorocyclopentene-based compounds oxidative ring opening of the ring-closed
      form is observed. However, the introduction of electroactive groups such as
      methoxyphenyl allows oxidative ring closure to occur in the hexafluoro compounds.
      The effect of electrolyte, solvent and temperature on the spectroelectrochemical
      properties were examined, and the switching process was found to be sensitive to
      the donor properties of the solvent/electrolyte system employed. In addition,
      thermally activated reversible isomerisation of the dicationic closed form was
      observed. The driving force for electrochemical ring opening and closure appears
      to be dependent on the relative stabilisation of the dicationic ring-open and
      ring-closed states. This study provides insight into the factors which determine
      the direction of cyclisation.

PMID- 16094679
TI  - Oxidative electrochemical switching in dithienylcyclopentenes, Part 2: effect of
      substitution and asymmetry on the efficiency and direction of molecular switching
      and redox stability.
AB  - The electrochemical and spectroelectrochemical properties of a series of C5
      substituted dithienylhexahydro- and dithienylhexafluorocyclopentenes are
      reported. The effect of substitution at C5 of the thienyl moiety on the redox
      properties is quite dramatic, in contrast to the effect on their photochemical
      properties. The efficiency of electrochemical switching is dependent both on the
      central cyclopentene unit and on the nature of the substituents, whereby electron
      donating moieties favour oxidative electrochemical ring-closure and vice versa.
      Asymmetrically substituted dithienylcyclopentenes were investigated to explore
      the ring-closure process in more detail. The results indicate that
      electrochemically induced ring-closure occurs via the monocation of the open
      form. In the presence of electroactive groups at C5 of the thienyl ring (e.g.,
      methoxyphenyl) initial oxidation of these groups is followed by intermolecular
      electron transfer, which drives ring-closure of the open forms.

PMID- 16094680
TI  - Regioselective conversion of the secondary hydroxyl groups of D-glucuronic acid
      without the requirement of O-protecting groups.
AB  - Trifluoromethanesulfonic acid anhydride (triflic acid anhydride) transforms the
      bicyclic thiazolidinlactam 1 a into the crystalline elimination product 2, in
      which all four secondary hydroxyl groups of 1 a are differently functionalized.
      Compound 2 can then add nucleophiles with high chemo- and stereoselectivity.
      Altogether, the four secondary hydroxyl groups of D-glucuronic acid are
      selectively transformed without the need for any O-protecting groups. Minimizing
      the number of O-protecting groups is a prerequisite for the use of sugar
      scaffolds in molecular libraries. The hapalosin analogues 15, 16, 19, and 22
      outline the strategy towards O-diversified glucose derivatives.

PMID- 16094681
TI  - Metal ions play different roles in the third-order nonlinear optical properties
      of d10 metal-organic clusters.

PMID- 16094682
TI  - Structural dualism in the zwitterionic 7-RR'NH-nido-7,8,9-C3B8H10 tricarbollide
      series: an example of absolute tautomerism.

PMID- 16094683
TI  - Origin of the high activity of second-generation Grubbs catalysts.

PMID- 16094684
TI  - Tungsten carbide microspheres as a noble-metal-economic electrocatalyst for
      methanol oxidation.

PMID- 16094685
TI  - The design and evaluation of heparin-binding foldamers.

PMID- 16094686
TI  - Domino reaction of 2,3-epoxy-1-alcohols and PIFA in the presence of H2O and the
      concise synthesis of (+)-tanikolide.

PMID- 16094687
TI  - An improvement in the bending ability of a hinged trisaccharide with the
      assistance of a sugar-sugar interaction.
AB  - Hinged di- and trisaccharides incorporating 2,4-diamino-beta-D-xylopyranoside as
      a hinge unit (Hin) were synthesized. Bridging of the diamino group of Hin by
      carbonylation or chelation to a metal ion results in a conformational change from
      (4)C1 to (1)C4, which in turn causes a bending of the oligosaccharides. In this
      study, the bending abilities of the hinged oligosaccharides were compared, in
      terms of the reactivities toward carbonylation and chelation. Di- or
      trisaccharides containing a 6-O-glycosylated mannopyranoside or galactopyranoside
      at their reducing ends had bending abilities similar to that of the Hin
      monosaccharide, probably because there were neither attractive nor repulsive
      interactions between the reducing and nonreducing ends. However, when Hin was
      attached at O2 of methyl mannopyranoside (Man alphaMe), the bending ability was
      dependent on the nonreducing sugar and the reaction conditions. Typically, a
      disaccharide--Hin beta(1,2)Man alphaMe--was difficult to bend under all the
      tested reaction conditions, and the bent population in the presence of Zn(II) was
      only 4%. On the other hand, a trisaccharide--Man alpha(1,3)Hin beta(1,2)Man
      alphaMe--was bent immediately after the addition of Zn(II) or Hg(II), and the
      bent population reached 75%, much larger than those of all the other hinged
      trisaccharides ever tested (<40%). This excellent bending ability suggests an
      attractive interaction between the reducing and nonreducing ends. The extended
      conformation was recovered by the addition of triethylenetetramine, a metal ion
      chelator. Reversible, quick, and efficient bending of the hinged trisaccharide
      was thus achieved.

PMID- 16094688
TI  - Anionic organic guests incorporated in zeolites: adsorption and reactivity of a
      Meisenheimer complex in faujasites.
AB  - Zeolites are suitable microporous hosts for positively charged organic species,
      but it is believed that they cannot adsorb organic anions. Pure Meisenheimer
      complex, derived from reduction of 2,4-dinitroaniline with NaBH4, was adsorbed
      inside faujasite cavities. Evidence for the internal incorporation of this
      negatively charged reaction intermediate comes from 1) XPS elemental analysis as
      a function of the depth of penetration into the particle, 2) the remarkable blue
      shift in lambda(max) of the Meisenheimer complex adsorbed on zeolite (ca. 470 nm)
      as compared to that in acetonitrile (580 nm) and 3) from the lack of reactivity
      with size-excluded hydride-acceptor reagents. Evidence is provided in support of
      an adsorption mechanism in which a neutral ion pair (alkali metal ion +
      Meisenheimer anion) is the actual species being adsorbed. In fact it appears that
      there is remarkable increase in the association constant for the ion-pair complex
      within the zeolite cavities as compared to DMF solution. Although this mechanism
      of adsorption as an ion-pair complex has precedents in the adsorption of some
      inorganic salts, what is novel is the notable increase in the stability and
      persistence of the Meisenheimer anion (a anionic reaction intermediate) as a
      result of zeolite inclusion. Adsorbed Meisenheimer complex exhibits much lower
      reactivity towards electron acceptors, oxygen, and water. Cyclic voltammetry of
      zeolite-modified electrodes reveals for the Meisenheimer complex adsorbed on LiY
      a reversible redox peak that is not observed in solution and has been interpreted
      as arising from site isolation and stabilisation of the electrochemically
      generated species.

PMID- 16094689
TI  - Human CXCR2 (hCXCR2) takes over functionalities of its murine homolog in hCXCR2
      knockin mice.
AB  - Human CXCR2 (hCXCR2) has been implicated in diverse inflammatory diseases. When
      roles of this receptor studied in animal models are extrapolated into men, large
      species differences in expression of the receptor and its ligands must be
      considered. These differences seriously weaken conclusions toward the role of
      hCXCR2 in the development of human diseases. It furthermore hampers
      straightforward testing of CXCR2 antagonists, especially when compounds
      discriminate between human and other species' receptors. Using gene targeting in
      embryonic stem cells, a hCXCR2 knockin mouse strain was generated in which
      endogenous murine CXCR2 (mCXCR2) sequences are replaced by the hCXCR2 gene.
      Correct targeting and expression on neutrophils were confirmed by Southern blot
      and immunohistochemical analyses. A phenotypic analysis of the hCXCR2 knockin
      mice, in comparison to wild-type and CXCR2 knockout mice, confirmed proper
      function of the hCXCR2 gene. In vivo migratory responses of neutrophils were
      intact in hCXCR2 knockin mice. Finally, an experiment with a CXCR2 antagonist
      demonstrated that the knockin model is indeed useful for in vivo evaluation of
      low-molecular weight compounds. In conclusion, our data unequivocally show that
      hCXCR2 can functionally replace mCXCR2, making this an attractive model to test
      novel pharmaceuticals designed to antagonize human CXCR2 in vivo.

PMID- 16094690
TI  - In vivo control of endosomal architecture by class II-associated invariant chain
      and cathepsin S.
AB  - The invariant chain (Ii) is a chaperone that regulates assembly and transport of
      class II MHC molecules. In the absence of the lysosomal protease cathepsin S
      (CatS), degradation of Ii is impaired and an Ii remnant that extends from the N
      terminus to about residue 110 accumulates in class II MHC-positive endosomal
      compartments, which are enlarged in size and lack multivesicular morphology. In
      primary B cells examined in vitro and in lymph nodes examined by immuno-electron
      microscopy, CatS controls architecture of class II-positive endosomal
      compartments. In a compound mutant mouse that lacks both CatS and Ii, the normal
      size of endosomes in class II-positive cells is restored, although internal
      endosomal membranes are absent. Proper degradation of Ii is thus essential for
      normal endosomal morphology in antigen-presenting cells in vivo.

PMID- 16094691
TI  - C-type lectin-independent interaction of complement opsonized HIV with monocyte
      derived dendritic cells.
AB  - HIV directly activates the complement cascade and is, therefore, opsonized with
      C3-cleavage products in vivo. This cloud of C3 fragments on the viral surface may
      impair the interaction of the HIV envelope glycoproteins gp120/gp41 with C-type
      lectins expressed on immature dendritic cells (iDC). Therefore, we determined the
      accessibility of gp120 after opsonization and compared the interaction of DC with
      non-opsonized or complement-opsonized HIV. The recognition of native gp120 was
      drastically impaired when the virus was covered by complement. Independent of
      opsonization, similar amounts of HIV bound to DC. The interaction of iDC and the
      infection of DC-PBL co-cultures with non-opsonized virus was significantly
      reduced by mannan and antibodies which inhibit the ICAM-1-CR3 interaction. The
      binding of opsonized virus to iDC was reduced by an anti-CR3-antibody, which
      interferes with the binding of C3 fragments, but was not affected by mannan.
      Complement enhanced the HIV infection of DC and DC-PBL co-cultures significantly.
      Mannan did not inhibit the complement-dependent enhancement of infection. Thus,
      non-opsonized and opsonized HIV interacted with iDC, although the binding
      mechanisms seemed to differ. As HIV is opsonized in vivo, the C-type lectin
      independent interaction of opsonized viruses with iDC has to be taken into
      account.

PMID- 16094692
TI  - Novel fluorescent phosphonic acid esters for discrimination of lipases and
      esterases.
AB  - Lipases and esterases are responsible for carboxylester hydrolysis inside and
      outside cells and are useful biocatalysts for (stereo)selective modification of
      synthetic substrates. Here we describe novel fluorescent suicide inhibitors that
      differ in structure and polarity for screening and discrimination of lipolytic
      enzymes in enzyme preparations. The inhibitors covalently react with the enzymes
      to form fluorescent lipid-protein complexes that can be resolved by gel
      electrophoresis. The selectivities of the inhibitors were determined by using
      different (phospho)lipase, esterase and cholesterol esterase preparations. The
      results indicate that formation of an inhibitor-enzyme complex is highly
      dependent on the chemical structure of the inhibitor. We identified inhibitors
      with very low specificity, and other derivatives that were highly specific for
      certain subgroups of lipolytic enzymes such as lipases and cholesterol esterases.
      A combination of these substrate-analogous activity probes represents a useful
      toolbox for rapid identification and classification of serine hydrolase enzymes.

PMID- 16094693
TI  - Altered specificity in DNA binding by the lac repressor: a mutant lac headpiece
      that mimics the gal repressor.
AB  - Recognition of the lac operator by the lac repressor involves specific
      interactions between residues in the repressor's recognition helix and bases in
      the DNA major groove. Tyr17 and Gln18, at positions 1 and 2 in the lac repressor
      recognition helix, can be exchanged for other amino acids to generate mutant
      repressors that display altered specificity. We have solved the solution
      structure of a protein-DNA complex of an altered-specificity mutant lac headpiece
      in which Tyr17 and Gln18 were exchanged for valine and alanine, respectively, as
      found in the recognition helix of the gal repressor. As previously described by
      Lehming et al. (EMBO J. 1987, 6, 3145-3153), this altered-specificity mutant of
      the lac repressor recognizes a variant lac operator that is similar to the gal
      operator Oe. The mutant lac headpiece showed the predicted specificity and is
      also able to mimic the gal repressor by recognizing and bending the natural gal
      operator Oe. These structural data show that, while most of the anchoring points
      that help the lac headpiece to assemble on the lac operator were preserved, a
      different network of protein-DNA interactions connecting Ala17 and Val18 to bases
      in the DNA major groove drives the specificity towards the altered operator.

PMID- 16094694
TI  - High-resolution solid-state NMR studies on uniformly [13C,15N]-labeled ubiquitin.
AB  - Understanding of the effects of intermolecular interactions, molecular dynamics,
      and sample preparation on high-resolution magic-angle spinning NMR data is
      currently limited. Using the example of a uniformly [13C,15N]-labeled sample of
      ubiquitin, we discuss solid-state NMR methods tailored to the construction of 3D
      molecular structure and study the influence of solid-phase protein preparation on
      solid-state NMR spectra. A comparative analysis of 13C', 13Calpha, and 13Cbeta
      resonance frequencies suggests that 13C chemical-shift variations are most likely
      to occur in protein regions that exhibit an enhanced degree of molecular
      mobility. Our results can be refined by additional solid-state NMR techniques and
      serve as a reference for ongoing efforts to characterize the structure and
      dynamics of (membrane) proteins, protein complexes, and other biomolecules by
      high-resolution solid-state NMR.

PMID- 16094695
TI  - Domain reorientation and induced fit upon RNA binding: solution structure and
      dynamics of ribosomal protein L11 from Thermotoga maritima.
AB  - L11, a protein of the large ribosomal subunit, binds to a highly conserved domain
      of 23S rRNA and mediates ribosomal GTPase activity. Its C-terminal domain is the
      main determinant for rRNA binding, whereas its N-terminal domain plays only a
      limited role in RNA binding. The N-terminal domain is thought to be involved in
      interactions with elongation and release factors as well as with the antibiotics
      thiostrepton and micrococcin. This report presents the NMR solution structure of
      the full-length L11 protein from the thermophilic eubacterium Thermotoga maritima
      in its free form. The structure is based on a large number of orientational
      restraints derived from residual dipolar couplings in addition to conventional
      NOE-based restraints. The solution structure of L11 demonstrates that, in
      contrast to many other multidomain RNA-binding proteins, the relative orientation
      of the two domains is well defined. This is shown both by heteronuclear 15N
      relaxation and residual dipolar-coupling data. Comparison of this NMR structure
      with the X-ray structure of RNA-bound L11, reveals that binding not only induces
      a rigidification of a flexible loop in the C-terminal domain, but also a sizeable
      reorientation of the N-terminal domain. The domain orientation in free L11 shows
      limited similarity to that of ribosome-bound L11 in complex with elongation
      factor, EF-G.

PMID- 16094696
TI  - NMR spectroscopy of paramagnetic metalloproteins.
AB  - This article deals with the solution structure determination of paramagnetic
      metalloproteins by NMR spectroscopy. These proteins were believed not to be
      suitable for NMR investigations for structure determination until a decade ago,
      but eventually novel experiments and software protocols were developed, with the
      aim of making the approach suitable for the goal and as user-friendly and safe as
      possible. In the article, we also give hints for the optimization of experiments
      with respect to each particular metal ion, with the aim of also providing a handy
      tool for nonspecialists. Finally, a section is dedicated to the significant
      progress made on 13C direct detection, which reduces the negative effects of
      paramagnetism and may constitute a new chapter in the whole field of NMR
      spectroscopy.

PMID- 16094697
TI  - Liver alveolar echinococcosis in China: clinical aspect with relative basic
      research.
AB  - This paper deals with all aspects of liver alveolar echin-ococcosis (AE)
      including epidemiology, pathology, clinical manifestations, imaging examinations,
      diagnosis and differential diagnosis, surgical treatment and chemotherapy. The
      review is not only based on personal clinical experiences but also in combination
      with relative basic research such as proliferation and growth of alveococcus,
      preclinical studies of a novel compound extracted from TCM for treatment of liver
      AE, and molecular immunology used for specific AE diagnosis, etc.

PMID- 16094698
TI  - Mutation of DNA polymerase beta in esophageal carcinoma of different regions.
AB  - AIM: To observe the variation of DNA polymerase beta (polbeta) in esophageal
      carcinoma. METHODS: Thirty specimens containing adjacent normal epithelial
      tissues were collected from patients in Linzhou region (a high risk area for
      esophageal squamous carcinoma) and 25 specimens were from a non-high risk area.
      Total RNA was extracted from the samples and reverse transcription polymerase
      chain reaction (RT-PCR) was performed. PCR products were cloned and sequenced to
      investigate the polbeta gene with DNASIS and OMIGA. Statistical significance was
      evaluated using the chi(2) test. RESULTS: High-incidence area group: polbeta gene
      variation was detected in 13 of 30 esophageal carcinoma tissue specimens, and
      only one variation was found in 30 corresponding adjacent normal tissue
      specimens. Non high-incidence area group: polbeta gene variation was detected in
      5 of 25 esophageal carcinoma tissue specimens, and no variation was found in 25
      corresponding adjacent normal tissue specimens. The incidence of polbeta gene
      variation observed in the high-incidence area group was significantly higher than
      in the non-high incidence area group. Two mutation hot spots (454-466 and 648-670
      nt) and a 58 bp deletion (177-234 nt) were found. CONCLUSION: Variations of
      polbeta perform different functions between the high-incidence areas and the
      other areas, and may play a more important role in the high-incidence areas.

PMID- 16094699
TI  - Gastric cancer surgery in cirrhotic patients: result of gastrectomy with D2 lymph
      node dissection.
AB  - AIM: To explore the feasibility of performing gastrectomy with D2 lymphadenectomy
      in gastric cancer patients with liver cirrhosis. METHODS: A total of 7,178
      patients were admitted with a diagnosis of liver cirrhosis from January 1993 to
      December 2003. We reviewed the records of 142 patients who were diagnosed with
      liver cirrhosis and gastric adenocarcinoma during the same period. Gastrectomy
      with D2 lymph node dissection for carcinoma of the stomach was performed in 94
      patients with histologically proven hepatic cirrhosis. RESULTS: All but 12
      patients were classified as Child's class A. Only 35 patients (37.2%) were
      diagnosed with cirrhosis before operation. Seventy-three patients underwent a
      subtotal gastrectomy (77.7%) and 21 patients (22.3%) underwent a total
      gastrectomy, each with D2 or more lymph node dissection. Two patients (3.8%) who
      had prophylactic intra-operative drain placement, died of postoperative
      complications from hepatorenal failure with intractable ascites. Thirty-seven
      patients (39.4%) experienced postoperative complications. The extent of gastric
      resection did not influence the morbidity whereas serum aspartate
      aminotransferase level (P = 0.011) and transfusion did (P = 0.008). The most
      common postoperative complication was ascites (13.9%) followed by wound infection
      (10.6%). CONCLUSION: We concluded that the presence of compensated cirrhosis,
      i.e. Child class A, is not a contraindication against gastrectomy with D2 or more
      lymph node dissection, when curative resection for gastric cancer is possible.
      Hepatic reserve and meticulous hemostasis are the likely determinants of
      operative prognosis.

PMID- 16094700
TI  - Altered profiles of nuclear matrix proteins during the differentiation of human
      gastric mucous adenocarcinoma MGc80-3 cells.
AB  - AIM: To find and identify specific nuclear matrix proteins associated with
      proliferation and differentiation of carcinoma cells, which will be potential
      markers for cancer diagnosis and targets in cancer therapy. METHODS: Nuclear
      matrix proteins were selectively extracted from MGc80-3 cells treated with or
      without hexamethylamine bisacetamide (HMBA), and subjected to 2-D gel
      electrophoresis. The resulted protein patterns were analyzed by Melanie software.
      Spots of nuclear matrix proteins differentially expressed were excised and
      subjected to in situ digestion with trypsin. Peptide masses were obtained by
      matrix-assisted laser-desorption/ionization time of flight mass spectrometry
      (MALDI-TOF-MS) analysis and submitted for database searching using Mascot tool.
      RESULTS: The MGc80-3 cells were induced into differentiation by HMBA. There were
      22 protein spots which changed remarkably in the nuclear matrix, from
      differentiation of MGc80-3 cells compared to control. Eleven of which were
      identified. Seven proteins--actin, prohibitin, porin 31HL, heterogeneous nuclear
      ribonucleoprotein A2/B1, vimentin, ATP synthase, and heat shock protein 60 were
      downregulated, whereas three proteins--heat shock protein gp96, heat shock
      protein 90-beta, and valosin-containing protein were upregulated, and the oxygen
      regulated protein was only found in the differentiated MGc80-3 cells. CONCLUSION:
      The induced differentiation of carcinoma cells is accompanied by the changes of
      nuclear matrix proteins. Further characterization of those proteins will show the
      mechanism of cellular proliferation and differentiation, as well as cancer
      differentiation.

PMID- 16094701
TI  - Histochemical studies on intestinal metaplasia adjacent to gastric cardia
      adenocarcinoma in subjects at high-incidence area in Henan, north China.
AB  - AIM: To characterize the histochemical type and pattern of intestinal metaplasia
      (IM) adjacent to gastric cardia adenocarcinoma (GCA) and distal gastric cancer
      (GC) in Linzhou, Henan Province, China. METHODS: Alcian-blue-periodic acid Schiff
      and high iron diamine-Alcian blue histochemical methods were performed on 142
      cases of IM, including 49 cases of GCA and 93 cases of GC. All the patients were
      from Linzhou, Henan Province, China, the highest incidence area for both GCA and
      squamous cell carcinoma. Radio- or chemotherapy was not applied to these patients
      before surgery. RESULTS: The detection rate of IM in tissues adjacent to GCA
      tissues was 44.9%, which was significantly lower than that in GC tissues (80.64%,
      P<0.01). The rates of both incomplete small intestinal and colonic IM types
      identified by histochemistry in GCA tissues (31.82% and 63.64%, respectively)
      were significantly higher than those in GC (5.33% and 21.33%, respectively,
      P<0.01). CONCLUSION: IM in GCA and GC should be considered as a separate entity.
      Further research is needed to evaluate whether neoplastic progression of IM is
      related to its mucin profile in GCA.

PMID- 16094702
TI  - Correlation between expression of cyclooxygenase-2 and the presence of
      inflammatory cells in human primary hepatocellular carcinoma: possible role in
      tumor promotion and angiogenesis.
AB  - AIM: To investigate the association of cyclooxygenase-2 (COX-2) expression with
      angiogenesis and the number and type of inflammatory cells (macrophages/Kupffer
      cells; mast cells) within primary hepatocellular carcinoma (HCC) tissues and
      adjacent non-tumorous (NT) tissues. METHODS: Immunohistochemistry for COX-2,
      CD34, CD68 and mast cell tryptase (MC(T)) was performed on 14 well-characterized
      series of liver-cirrhosis-associated HCC patients. COX-2 expression and the
      number of inflammatory cells in tumor lesions and surrounding liver tissues of
      each specimen were compared. Moreover, COX-2, CD34 staining and the number of
      inflammatory cells in areas with different histological degrees within each tumor
      sample were comparatively analyzed. RESULTS: The percentage of COX-2 positive
      cells was significantly higher in NT tissues than in tumors. COX-2 expression was
      higher in well-differentiated HCC than in poorly-differentiated tissues. Few mast
      cells were observed within the tumor mass, whereas a higher number was observed
      in the surrounding tissue, especially in peri-portal spaces of NT tissues.
      Abundant macrophages/Kupffer cells were observed in NT tissues, whereas the
      number of cells was significantly lower in the tumor mass. However, a higher cell
      number was observed in the well-differentiated tumor and progressively decreased
      in relation to the differentiation grade. Within the tumor, a positive
      correlation was found between COX-2 expression and the number of
      macrophages/Kupffer cells and mast cells. Moreover, there was a positive
      correlation between CD34 and COX-2 expression in tumor tissues. Comparison
      between well- and poorly-differentiated HCC showed that the number of CD34
      positive cells decreased with dedifferentiation. However, COX-2 was the only
      independent variable showing a positive correlation with CD34 in a multivariate
      analysis. CONCLUSION: The presence of inflammatory cells and COX-2 expression in
      liver tumor suggests a possible relationship with tumor angiogenesis. COX-2
      expressing cells and the number of macrophages/Kupffer cells and mast cells
      decrease with progression of the disease.

PMID- 16094703
TI  - Nitrative and oxidative DNA damage in intrahepatic cholangiocarcinoma patients in
      relation to tumor invasion.
AB  - AIM: Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8
      dihydro-2'-deoxyguanosine (8-oxodG) formation has been implicated in initiation
      and/or promotion of inflammation-mediated carcinogenesis. The aim of this study
      is to clarify whether these DNA lesions participate in the progression of
      intrahepatic cholangiocarcinoma. METHODS: We investigated the relation of the
      formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible
      factor-1alpha (HIF-1alpha) with tumor invasion in 37 patients with intra-hepatic
      cholangiocarcinoma. RESULTS: Immunohistochemical analyses revealed that 8
      nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous
      tissues than in non-cancerous tissues. HIF-1alpha could be detected in cancerous
      tissues in all patients, suggesting low oxygen tension in the tumors. HIF-1alpha
      expression was correlated with inducible nitric oxide synthase (iNOS) expression
      (r = 0.369 and P = 0.025) and 8-oxodG formation (r = 0.398 and P = 0.015). Double
      immunofluorescence study revealed that iNOS and HIF-1alpha co-localized in
      cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly
      with lymphatic invasion (r = 0.386 and P = 0.018). Moreover, 8-nitroguanine and 8
      oxodG in non-cancerous tissues were associated significantly with neural invasion
      (P = 0.042 and P = 0.026, respectively). These results suggest that reciprocal
      activation between HIF-1alpha and iNOS mediates persistent DNA damage, which
      induces tumor invasiveness via mutations, resulting in poor prognosis.
      CONCLUSION: The formation of 8-nitroguanine and 8-oxodG plays an important role
      in multiple steps of genetic changes leading to tumor progression, including
      invasiveness.

PMID- 16094704
TI  - Functional expression of a proliferation-related ligand in hepatocellular
      carcinoma and its implications for neovascularization.
AB  - AIM: To detect the expression of a proliferation-related ligand on human
      hepatocellular carcinoma (HCC) cell lines (SK-Hep1, HLE and HepG2) and in culture
      medium. METHODS: APRIL expression was analyzed by Western blotting in HCC cell
      lines. Effects of APRIL to cell count and angiogenesis were analyzed, too.
      RESULTS: Recombinant human APRIL (rhAPRIL) increased cell viability of HepG2
      cells and, in HUVEC, rhAPRIL provided slight tolerance to cell death from serum
      starvation. Soluble APRIL (sAPRIL) from HLE cells increased after serum
      starvation, but did not change in SK-Hep1 or HepG2 cells. These cells showed down
      regulation of VEGF after incubation with anti-APRIL antibody. Furthermore,
      culture medium from the HCC cells treated with anti-APRIL antibody treatment
      inhibited tube formation of HUVECs. CONCLUSION: Functional expression of APRIL
      might contribute to neovascularization via an upregulation of VEGF in HCC.

PMID- 16094705
TI  - Expression and alteration of insulin-like growth factor II-messenger RNA in
      hepatoma tissues and peripheral blood of patients with hepatocellular carcinoma.
AB  - AIM: To investigate the clinical values of serum free insulin-like growth factor
      II (IGF-II) levels and IGF-II mRNA in hepatocellular carcinoma (HCC) tissues and
      peripheral blood for diagnosis of HCC and monitoring of extrahepatic metastasis.
      METHODS: Total RNAs were extracted from HCC tissues or peripheral blood
      mononuclear cells from patients with HCC, liver diseases devoid of cancer, non
      hepatic tumors, and healthy controls, respectively. IGF-II cDNAs were synthesized
      through random primers and reverse-transcriptase, amplified by polymerase chain
      reaction (PCR), and confirmed by DNA sequencing analysis. Serum free IGF-II
      levels in patients with different liver diseases were analyzed by an enzyme
      linked immunosorbent assay. RESULTS: The amplified fragments of IGF-II mRNA by RT
      PCR were identical to originally designed ones with a size of 170 bp and
      confirmed by sequencing analysis. The dilution experiments revealed that the
      lowest sensitivity of our system was 2 ng/L of total RNA. The positive
      frequencies of IGF-II mRNA were 100% in HCC tissues, 53.3% in para-cancerous
      tissues, and 0% in non-cancerous tissues, respectively. The serum free IGF-II
      levels were significantly higher in HCC than those in chronic hepatitis or liver
      cirrhosis. The positive frequency of circulating IGF-II mRNA was 34.2% in HCC, no
      amplified fragment was found in other liver diseases, extrahepatic tumors, and
      normal controls, respectively. The circulating IGF-II mRNA correlated with the
      stage of HCC, and its positive rate was 100% in HCC with extrahepatic metastasis
      and 35.5% in HCC with AFP-negative. No significant correlation was found between
      tumor sizes and circulating IGF-II mRNA fragment. CONCLUSION: The abnormal
      expressions of free IGF-II and IGF-II mRNA are useful tumor markers for HCC
      diagnosis, differentiation of extrahepatic metastasis and monitoring
      postoperative recurrence.

PMID- 16094706
TI  - Expression of MUC1 and its significance in hepatocellular and cholangiocarcinoma
      tissue.
AB  - AIM: To investigate the relation between MUC1 expression, distribution, and
      prognosis in hepatocellular and cholangiocarcinoma (HCC and CC) and cirrhotic
      liver tissues, and their significance in HCC and CC diagnosis. METHODS:
      Expression and distribution of MUC1 were examined by immunohistochemical assay
      with anti-MUC1 mAb in 59 samples of HCC and 37 samples of CC, 20 samples of
      cirrhotic liver tissues, and 10 samples of normal liver tissues, seeking possible
      associations between MUC1 positive expression, distribution in HCC and CC
      (primary liver cancer, PLC) cases and the studied clinical data. RESULTS:
      Immunohistochemical analysis of MUC1 expression showed that in the 96 PLC
      samples, 68 (70.8%) were strong positive, and 6 (6.2%) were weak positive. Only 4
      in the 20 cirrhotic liver tissues were found to be weak positive, while no
      expression of MUC1 was detected in normal liver tissues. Apparently, the high
      expression rate of MUC1 in PLC tissues was statistically significant in
      comparison to that in cirrhotic and normal liver tissues. The expressed MUC1
      protein, stained in dark brownish or brownish-yellow particles, chiefly localized
      on the cancer cell membranes or in cytoplasm. In the 68 strong positive samples,
      40 were detected on cell membrane and the other 28 were in cytoplasm. In
      addition, follow-up studies of those PLC cases demonstrated that MUC1 expression
      on cell membrane or in cytoplasm was closely associated with PLC prognosis. The
      expression of MUC1 in PLC had little statistical significance in respect of the
      pathological types and sizes of the tumors, but a strong relationship regarding
      histological differentiation, metastasis of lymph nodes, portal canal emboli, and
      post-operational recurrence of the carcinomas. After 3 years of tumor excision,
      the metastasis rate in MUC1 positive expression group (67.6%) was much higher
      than that in MUC1 weak expression group (33.3%) and negative expression group
      (31.8%), and thus the survival rate in MUC1-positive expression group was
      significantly different from that in weak and negative expression groups.
      CONCLUSION: Expression and localization of MUC1 proteins in primary liver
      carcinomas (PLCs) may act as prognostic markers, and MUC1 molecules might be
      helpful in differential diagnosis.

PMID- 16094707
TI  - Role of cell adhesion signal molecules in hepatocellular carcinoma cell
      apoptosis.
AB  - AIM: Cell adhesion molecules and their signal molecules play a very important
      role in carcinogenesis. The aim of this study is to elucidate the role of these
      molecules and the signal molecules of integrins and E-cadherins, such as (focal
      adhesion kinase) FAK, (integrin linked kinase) ILK, and beta-catenin in
      hepatocellular carcinoma cell apoptosis. METHODS: We first synthesized the small
      molecular compound, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and identified it,
      by element analysis and (1)H NMR. To establish the apoptosis model of the SMMC
      7721 hepatocellular carcinoma cell, we treated cells with DCVC in EBSS for
      different concentrations or for various length times in the presence of 20
      micromol/L N,N'-diphenyl-p-phenylenediamine, which blocks necrotic cell death and
      identified this model by flow cytometry and DNA ladder. Then we studied the
      changes of FAK, ILK, beta-catenin, and PKB in this apoptotic model by Western
      blot. RESULTS: We found that the loss or decrease of cell adhesion signal
      molecules is an important reason in apoptosis of SMMC-7721 hepatocellular
      carcinoma cell and the apoptosis of SMMC-7721 cell was preceded by the loss or
      decrease of FAK, ILK, PKB, and beta-catenin or the damage of cell-matrix and cell
      cell adhesion. CONCLUSION: Our results suggested that the decrease of adhesion
      signal molecules, FAK, ILK, PKB, and beta-catenin, could induce hepatocellular
      carcinoma cell apoptosis.

PMID- 16094708
TI  - Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer
      cell line, SNU-C4.
AB  - AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in
      plants, are known to have antioxidant and anti-cancer effects. We investigated
      whether the anti-cancer effects of the OPC are induced by apoptosis on human
      colorectal cancer cell line, SNU-C4. METHODS: Colorectal cancer cell line, SNU-C4
      was cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. The
      cytotoxic effect of OPC was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenylt-etrazolium bromide (MTT) assay. To find out the apoptotic cell death,
      4, 6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl
      transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse
      transcription-polymerase chain reaction (RT-PCR), and caspase-3 enzyme assay were
      performed. RESULTS: In this study, cytotoxic effect of OPC on SNU-C4 cells
      appeared in a dose-dependent manner. OPC treatment (100 microg/mL) revealed
      typical morphological apoptotic features. Additionally OPC treatment (100
      microg/mL) increased level of BAX and CASPASE-3, and decreased level of BCL-2
      mRNA expression. Caspase-3 enzyme activity was also significantly increased by
      treatment of OPC (100 microg/mL) compared with control. CONCLUSION: These data
      indicate that OPC caused cell death by apoptosis through caspase pathways on
      human colorectal cancer cell line, SNU-C4.

PMID- 16094709
TI  - Identification of proteins of human colorectal carcinoma cell line SW480 by two
      dimensional electrophoresis and MALDI-TOF mass spectrometry.
AB  - AIM: To conduct the proteomic analysis of human colorectal carcinoma cell line,
      SW480 by using two-dimensional electrophoresis (2-DE) and matrix-assisted laser
      desorption /ionization-time of flight mass spectrometry (MALDI-TOFMS). METHODS:
      The total proteins of human colorectal carcinoma cell line, SW480 were separated
      with 2-DE by using immobilized pH gradient strips and visualized by staining with
      silver nitrate. The gel images were acquired by scanner and 2-DE analysis
      software, Image Master 2D Elite. Nineteen distinct protein spots were excised
      from gel randomly and digested in gel by TPCK-trypsin. Mass analysis of the
      tryptic digest peptides mixture was performed by using MALDI-TOF MS. Peptide mass
      fingerprints (PMFs) obtained by the MALDI-TOF analysis were used to search NCBI,
      SWISS-PROT and MSDB databases by using Mascot software. RESULTS: PMF maps of all
      spots were obtained by MALDI-TOF MS and thirteen proteins were preliminarily
      identified. CONCLUSION: The methods of analysis and identification of protein
      spots of tumor cells in 2-DE gel with silver staining by MALDI-TOF MS derived PMF
      have been established. Protein expression profile of SW480 has been obtained. It
      is demonstrated that a combination of proteomics and cell culture is a useful
      approach to comprehend the process of colon carcinogenesis.

PMID- 16094710
TI  - Changing patterns of colorectal cancer in China over a period of 20 years.
AB  - AIM: To determine whether any changes have occurred on the patterns of colorectal
      cancer in China. METHODS: Data from 21 Chinese articles published from 1980 to
      1999, were used to analyze the time trend of colorectal cancer according to the
      patients' age at diagnosis, sex, the site of the tumor, stage, and the pathology.
      RESULTS: From 1980s to 1990s, the mean age of the colorectal cancer patients has
      increased. The percentage of the female patients rose. The distribution of
      colorectal carcinoma shows a predominance of rectal cancer. However, the
      proportion of proximal colon cancer (including transverse and ascending colon)
      increased significantly accompanied by a decline in the percentage of rectal
      cancer. Similarity in the percentage of distal colon cancer between two decades
      was revealed. In the 1990s, statistically more Stage B patients were found than
      those in 1980s. In addition, databases show a significant decrease in the Stage D
      cases. The proportion of adenocarcinoma increased, but the mucinous
      adenocarcinoma decreased during two decades. CONCLUSION: These findings indicate
      that the pattern of colorectal cancer in China has been changing. Especially, a
      proximal shift due to the increasing proportion of ascending and transverse colon
      cancer has occurred in China.

PMID- 16094711
TI  - Expression of a novel apoptosis inhibitor-survivin in colorectal carcinoma.
AB  - AIM: To investigate the role of survivin expression in the pathogenesis of
      colorectal carcinoma. METHODS: Immunohistochemistry S-P method and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were used to
      detect the expression of survivin and apoptotic cell in situ in colorectal
      cancerous tissues, para-cancerous tissues and normal tissues of 48 cases of
      colorectal carcinoma. RESULTS: The survivin positive unit (PU) was higher in
      cancerous tissues (38.76+/-5.14) than in para-cancerous (25.17+/-7.26) or normal
      tissues (0.57+/-0.03) (P<0.05). The apoptosis index (AI) of para-cancerous
      tissues was (7.51+/-2.63%) higher than cancerous tissues (4.65+/-1.76%). The
      expression of survivin was associated with pathological grade, lymph node
      metastasis and Dukes stage of colorectal carcinoma. CONCLUSION: Survivin
      expression may play an important role in carcinogenesis of colorectal carcinoma
      and may be associated with malignant biological behaviors of colorectal
      carcinoma.

PMID- 16094712
TI  - Mutations in hepatitis B virus core regions correlate with hepatocellular injury
      in Chinese patients with chronic hepatitis B.
AB  - AIM: To elucidate the relationship between the frequency of core mutations and
      the clinical activity of hepatitis B virus (HBV)-related liver disease and to
      characterize the amino acid changes in the core region of HBV. METHODS: We
      studied 17 Chinese patients with chronic hepatitis B according to their clinical
      courses and patterns of the entire core region of HBV. RESULTS: Amino acid
      changes often appeared in the HBV core region of the HBV gene in patients with
      high values of alanine aminotransferase (ALT) or with the seroconversion from
      HbeAg to anti-HBe. The HBV core region with amino acid changes had high frequency
      sites that corresponded to HLA I/II restricted recognition epitopes reported by
      some investigators. CONCLUSION: The core amino acid changes of this study occur
      due to influence of host immune system. The presence of mutations in the HBV core
      region seems to be important for predicting the clinical activity of hepatitis B
      in Chinese patients.

PMID- 16094713
TI  - Blood micronutrient, oxidative stress, and viral load in patients with chronic
      hepatitis C.
AB  - AIM: To assess the extent of micronutrient and oxidative stress in blood and to
      examine their linkages with viral loads in chronic hepatitis C patients. METHODS:
      Hepatitis C virus (HCV)-RNA levels were quantified in the serum from 37
      previously untreated patients with chronic hepatitis C. The plasma and
      erythrocyte micronutrients (zinc, selenium, copper, and iron) were estimated, and
      malondialdehyde (MDA) contents were determined as a marker to detect oxidative
      stress. Antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase
      (GPX) and glutathione reductase (GR) activities in blood were also measured. The
      control group contained 31 healthy volunteers. RESULTS: The contents of zinc
      (Zn), and selenium (Se) in plasma and erythrocytes were significantly lower in
      hepatitis C patients than in the controls. On the contrary, copper (Cu) levels
      were significantly higher. Furthermore, plasma and erythrocyte MDA levels, and
      the SOD and GR activities in erythrocytes significantly increased in hepatitis C
      patients compared to the controls. However, the plasma GPX activity in patients
      was markedly lower. Plasma Se (r = -0.730, P<0.05), Cu (r = 0.635), and GPX (r = 
      0.675) demonstrated correlations with HCV-RNA loads. Significant correlation
      coefficients were also observed between HCV-RNA levels and erythrocyte Zn (r = 
      0.403), Se (r = -0.544), Cu (r = 0.701) and MDA (r = 0.629) and GR (r = 0.441).
      CONCLUSION: The levels of Zn, Se, Cu, and oxidative stress (MDA), as well as
      related anti-oxidative enzymes (GR and GPX) in blood have important impact on the
      viral factors in chronic hepatitis C. The distribution of these parameters might
      be significant biomarkers for HCV.

PMID- 16094714
TI  - Biological impacts of "hot-spot" mutations of hepatitis B virus X proteins are
      genotype B and C differentiated.
AB  - AIM: To investigate the biological impacts of "hot-spot" mutations on genotype B
      and C HBV X proteins (HBx). METHODS: Five types of "hot-spot" mutations of
      genotype B or C HBV X genes, which sequentially lead to the amino acid
      substitutions of HBx as I127T, F132Y, K130M+V131I, I127T+K130M+V131I, or
      K130M+V131I+F132Y, respectively, were generated by means of site-directed
      mutagenesis. To evaluate the anti-proliferative effects, HBx or related mutants'
      expression vectors were transfected separately to the Chang cells by
      lipofectamine, and the cells were cultured in hygromycin selective medium for 14
      d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa
      dyes and scored (increase of the colonies indicated the reduction of the anti
      proliferation activity, and vice versa). Different types of HBx expression
      vectors were co-transfected separately with the reporter plasmid pCMVbeta to
      Chang cells, which were lysed 48 h post-transfection and the intra-cellular beta
      galactosidase activities were monitored (increase of the beta-galactosidase
      activities indicated the reduction of the transactivation activity, and vice
      versa). All data obtained were calculated by paired-samples t-test. RESULTS: As
      compared to standard genotype B HBx, mutants of I127T and I127T+K130M+V131I
      showed higher transactivation and anti-proliferative activities, while the
      mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As
      compared to standard genotype C HBx, I127T mutant showed higher transactivation
      activity, while the other four types of mutants showed no differences. With
      regard to anti-proliferative activity, compared to standard genotype C HBx, F132Y
      and K130M+ V131I mutants showed lower activities, and K130M+V131I +F132Y mutant,
      on the other hand, showed higher activity, while the mutants of I127T and
      I127T+K130M+V131I showed no differences. CONCLUSION: "Hot-spot" mutations affect
      the anti-proliferation and transactivation activities of genotype B and/or C HBx,
      and the biological impacts of most "hot-spot" mutations on HBx are genotype B and
      C differentiated.

PMID- 16094715
TI  - Screening of genes of proteins interacting with p7 protein of hepatitis C virus
      from human liver cDNA library by yeast two-hybrid system.
AB  - AIM: To investigate the biological function of p7 protein and to look for
      proteins interacting with p7 protein in hepatocytes. METHODS: We constructed p7
      protein bait plasmid by cloning the gene of p7 protein into pGBKT7, then
      transformed it into yeast AH109 (a type). The transformed yeast was mated with
      yeast Y187 (alpha type) containing liver cDNA library plasmid, pACT2 in 2XYPDA
      medium. Diploid yeast was plated on synthetic dropout nutrient medium (SD/-Trp
      Leu-His-Ade) containing x-alpha-gal for selection and screening. After extracting
      and sequencing of plasmids from blue colonies, we performed sequence analysis by
      bioinformatics. RESULTS: Fifty colonies were selected and sequenced. Among them,
      one colony was Homo sapiens signal sequence receptor, seven colonies were Homo
      sapiens H19, seven colonies were immunoglobulin superfamily containing leucine
      rich repeat, three colonies were spermatid peri-nuclear RNA binding proteins, two
      colonies were membrane-spanning 4-domains, 24 colonies were cancer-associated
      antigens, four colonies were nucleoporin 214 ku and two colonies were CLL
      associated antigens. CONCLUSION: The successful cloning of gene of protein
      interacting with p7 protein paves a way for the study of the physiological
      function of p7 protein and its associated protein.

PMID- 16094716
TI  - Implications of anti-parietal cell antibodies and anti-Helicobacter pylori
      antibodies in histological gastritis and patient outcome.
AB  - AIM: To develop a serum or histological marker for early discovery of gastric
      atrophy or intestinal metaplasia. METHODS: This study enrolled 44 patients with
      gastric adenocarcinoma, 52 patients with duodenal ulcer, 14 patients with gastric
      ulcer and 42 consecutive healthy adults as controls. Each patient received an
      endoscopy and five biopsy samples were obtained. The degrees of histological
      parameters of gastritis were categorized following the Updated Sydney System.
      Anti-parietal cell antibodies (APCA) and anti-Helicobacter pylori (H pylori)
      antibodies (AHPA) were analyzed by immunoassays. H pylori infection was diagnosed
      by rapid urease test and histological examination. RESULTS: Patients with gastric
      cancer and gastric ulcer are significantly older than healthy subjects, while
      also displaying higher frequency of APCA than healthy controls. Patients with
      positive APCA showed higher scores in gastric atrophy and intestinal metaplasia
      of corpus than patients with negative APCA. Patients with positive AHPA had
      higher scores in gastric atrophy, intestinal metaplasia, and gastric inflammation
      of antrum than those patients with negative AHPA. Elderly patients had greater
      prevalence rates of APCA. Following multivariant logistic regression analysis,
      the only significant risk factor for antral atrophy is positive AHPA, while that
      for corpus atrophy is positive APCA. CONCLUSION: The existence of positive APCA
      correlates with glandular atrophy in corpus and the presence of positive AHPA
      correlates with glandular atrophy in antrum. The existence of serum APCA and AHPA
      betokens glandular atrophy and requires further examination for gastric cancer.

PMID- 16094717
TI  - Long-term omeprazole and esomeprazole treatment does not significantly increase
      gastric epithelial cell proliferation and epithelial growth factor receptor
      expression and has no effect on apoptosis and p53 expression.
AB  - AIM: To study the effect of proton pump inhibitor (PPI) treatment on patients
      with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal
      growth factor receptor (EGFR) expression. METHODS: After informed consent was
      obtained, gastric biopsies of the antrum were taken from patients with reflux
      oesophagitis prior to and after 6 mo of 20 mg omeprazole (n = 14) or 40 mg
      esomeprazole (n = 12) therapy. Patients did not take any other medications known
      to affect the gastric mucosa. All patients were Helicobacter pylori negative as
      confirmed by rapid urease test and histology, respectively. Cell proliferation,
      apoptosis, EGFR, and p53 expression were measured by immunohistochemical
      techniques. At least 600 glandular epithelial cells were encountered and results
      were expressed as percentage of total cells counted. Was considered statistically
      significant. RESULTS: Although there was a trend towards increase of cell
      proliferation and EGFR expression both in omeprazole and esomeprazole treated
      group, the difference was not statistically significant. Neither apoptosis nor
      p53 expression was affected. CONCLUSION: Long-term PPI treatment does not
      significantly increase gastric epithelial cell proliferation and EGFR expression
      and has no effect on apoptosis and p53 expression.

PMID- 16094718
TI  - Prevalence of porcine endogenous retrovirus in Chinese pig breeds and in patients
      treated with a porcine liver cell-based bioreactor.
AB  - AIM: To determine the prevalence of porcine endogenous retrovirus (PERV) in
      various pig breeds raised in China including Chinese experimental mini-pigs by
      PERV-reverse transcriptase (PERV-RT enzyme). Moreover, the potential for
      infection of PERV was investigated in patients treated with a bioreactor based on
      porcine liver cells (n = 3). METHODS: Pig serum, liver and muscle cell-free
      supernatants were collected from various Chinese pig breeds. Porcine hepatocytes
      were isolated with a two-step perfusion method. Three patients with acute or
      chronic liver failure were treated with a bioartificial liver support system
      (BALSS) for 8-12 h and serum samples were collected from the patients before,
      immediately after and 30 d after treatment. RESULTS: The activities of PERV-RT
      enzyme in pig liver and muscle cell-free supernatants were higher than in normal
      human controls. PERV-TR enzyme activity did not increase in patients before and
      after 1 mo of treatment. PERV-RT activities were not significantly different when
      compared with pre-treatment group (1.544+/-0.155576), the post-treatment groups
      (1.501+/-0.053507, 1.461+/-0.033808 and 1.6006667+/-0.01963 for 0, 14 and 30 d
      post-treatment, respectively, P>0.05), and normal control group (1.440+/- 1.0641,
      P>0.05). RT enzyme activity in Chinese experimental mini-pigs was higher than in
      normal human control group (1.440+/-1.0641 U/mL, P<0.05), and not significantly
      different (P>0.05) when compared with the pig breeds except in the muscle
      supernatants. All the samples including muscle and liver cell supernatants from
      the Chinese mini-experimental pigs and the four domestic Chinese pig breeds
      contained PERVs. CONCLUSION: These results suggest that the risk of PERV
      infection through BALSS containing porcine liver cells without immunosuppressants
      may be quite low. Although there were PERVs in Chinese experimental mini-pigs and
      porcine liver cell culture suspensions, we did not find any evidence of
      persistent PERV infection in patients treated with this porcine hepatocyte-based
      bioartificial liver.

PMID- 16094719
TI  - Prevalence of advanced colonic polyps in asymptomatic Chinese.
AB  - AIM: To investigate the prevalence of advanced polyps in asymptomatic Chinese and
      to determine the risk of proximal advanced colonic polyps in subjects with and
      without polyps in the distal colon. METHODS: Data were collected prospectively
      during colonoscopic examinations performed in 5 973 subjects as part of health
      evaluation at our unit from December 1997 to December 2003. Polyps were
      considered advanced, if they were larger than 10 mm or were tubovillous, villous
      or malignant. Proximal colon was defined as the splenic flexure and more proximal
      portions of the colon. RESULTS: Colon polyps were detected in 971 (16.3%)
      subjects (613 males and 358 females) with their mean age being 56.6+/-10.7 years.
      Advanced polyps were noted in 199 (3.3%) individuals. Subjects were sub
      classified according to the location of polyps into three groups: distal (569,
      58.6%), proximal (284, 29.2%), and combined proximal and distal (118, 12.2%)
      groups. Subjects with advanced polyps in these three groups were 95 (9.8%), 56
      (5.8%), and 48 (4.9%) respectively. In the 48 subjects with advanced combined
      polyps, 13 advanced polyps were distributed at the distal colon, 17 at the
      proximal colon, and 18 at both. Eighteen colon cancers including 12 at sigmoid
      and 6 at ascending colon were confirmed by final pathology. The relative risk for
      advanced proximal polyp according to distal findings was 3.1 (95%CI: 1.3-7.4) for
      hyperplastic polyp, 2.7 (95%CI: 1.4-5.3) for tubular polyp and 13.5 (95%CI: 5.1
      35.4) for advanced polyp as compared to that for no polyp. However, 56 (28.2%) of
      199 subjects with advanced polyps had no index polyps at the distal colon and
      might go undetected under sigmoidoscopic screening. CONCLUSION: Although distal
      lesions can predict the risk of advanced proximal polyps, a substantial portion
      of Chinese with advanced proximal polyps is not associated with any distal
      sentinel lesions. These data have implications for screening policy of colon
      cancers in Taiwanese Chinese.

PMID- 16094720
TI  - Effect of ligand of peroxisome proliferator-activated receptor gamma on the
      biological characters of hepatic stellate cells.
AB  - AIM: To study the effect of rosiglitazone, which is a ligand of peroxisome
      proliferator-activated receptor gamma (PPARgamma), on the expression of PPARgamma
      in hepatic stellate cells (HSCs) and on the biological characteristics of HSCs.
      METHODS: The activated HSCs were divided into three groups: control group, 3
      micromol/L rosiglitazone group, and 10 micromol/L rosiglitazone group. The
      expression of PPARgamma, alpha-smooth muscle actin (alpha-SMA), and type I and
      III collagen was detected by RT-PCR, Western blot and immunocytochemical
      staining, respectively. Cell proliferation was determined with
      methylthiazolyltetrazolium (MTT) colorimetric assay. Cell apoptosis was
      demonstrated with flow cytometry. RESULTS: The expression of PPARgamma at mRNA
      and protein level markedly increased in HSCs of 10 micromol/L rosiglitazone group
      (t value was 10.870 and 4.627 respectively, P<0.01 in both). The proliferation of
      HSCs in 10 micromol/L rosiglitazone group decreased significantly (t = 5.542,
      P<0.01), alpha-SMA expression level and type I collagen synthesis ability were
      also reduced vs controls (t value = 10.256 and 14.627 respectively, P<0.01 in
      both). The apoptotic rate of HSCs significantly increased in 10 micromol/L
      rosiglitazone group vs control (chi(2) = 16.682, P<0.01). CONCLUSION: By
      increasing expression of PPARgamma in activated HSCs, rosiglitazone, an agonist
      of PPARgamma, decreases alpha-SMA expression and type I collagen synthesis,
      inhibits cell proliferation, and induces cell apoptosis.

PMID- 16094721
TI  - Dynamic expression of apoptosis-related genes during development of laboratory
      hepatocellular carcinoma and its relation to apoptosis.
AB  - AIM: To explore the expression of p53, bcl-2, bax, survivin and the cell
      apoptosis during the development of tree shrew hepatocellular carcinoma (HCC),
      the relationship between expression of these genes, its impact on HCC
      development, and its relation to cell apoptosis. METHODS: Tree shrew HCC was
      induced with aflatoxin B1 (AFB1), and regular biopsy of liver tissues was carried
      out and the biopsy tissues were collected during cancer inducement. Liver biopsy
      tissue and HCC tissue were collected from 35 pre-cancerous experimental animals
      at wk 30 and 60 and at the 30th-, 60th-, and 90th-wk. Liver biopsy tissues were
      collected from 13 blank control animals at wk 30, 60, and 90. Expression of p53,
      bcl-2, bax, and survivin at each stage was examined by immunohistochemistry
      method. Apoptotic cells were detected in situ by the terminal deoxynucleotidyl
      transferase-mediated nick end labeling (TUNEL) technique. RESULTS: The apoptosis
      rate of normal hepatic cells was extremely low, whereas it increased during the
      formation of HCC. Expression of the apoptosis-related genes p53, bcl-2, bax, and
      survivin during the formation of HCC presented an increasing tendency. Expression
      of p53 did not noticeably relate to that of bcl-2, bax, and survivin, whereas
      expression of bcl-2 and bax was closely related. In HCC, p53 did not present a
      distinct relation to cell apoptosis, whereas its high level expression was
      probably related to liver cell proliferation. Survivin negatively correlated
      apoptosis index, and its overexpression could inhibit cell apoptosis. CONCLUSION:
      Apoptosis-related genes p53, bcl-2, bax, and survivin are all related to the
      occurrence of HCC. The anti-apoptosis effect of bcl-2 is influenced by bax, and
      ratio bcl/bax reflects more correctly the extent of cell apoptosis.

PMID- 16094722
TI  - Resveratrol prolongs allograft survival after liver transplantation in rats.
AB  - AIM: To study the immuno-modulatory effect of resveratrol (RES) on allograft
      rejection after liver transplantation in rats. METHODS: Male Sprague-Dawley (SD)
      rats were selected as donors and male Wistar rats as recipients for a rejection
      model. The recipients were divided into four groups after orthotopic liver
      transplantation (OLTx). In the RES A, B, and C groups, RES was given intra
      peritoneally once a day (25, 50, and 100 mg/kg, respectively) after OLTx, whereas
      in the control group, vehicle buffer was given intra-peritoneally once a day. The
      survival time, serum chemistry, production of cytokines, activation of
      transcription factor NF-kappaB, and histopathologic findings were then compared
      among these groups. RESULTS: The mean survival time after OLTx in the RES C group
      was significantly longer than that in the control group (16.7+/-1.2 d vs 9.3+/
      0.6 d, P<0.01). On the 7th post-transplant day the serum albumin level
      significantly improved in the RES C group, the serum total bile acid and alanine
      aminotransferase (ALT) levels were significantly lower in the RES C group, the
      serum IL-2 and INF-gamma levels were significantly lower in the RES C group, and
      the activation of transcription factor NF-kappaB in peripheral blood T
      lymphocytes was significantly suppressed in the RES A, B, and C groups in
      comparison to those in the control group. On the 7th post-transplant day, a
      histological examination revealed apparent difference in the severity of
      rejection between the RES C group and control group. CONCLUSION: RES has an
      immuno-suppressive property as well as protective effect on hepatocytes under
      allograft rejection. It might serve as a novel agent for reducing the severity of
      hepatic allograft rejection in rats.

PMID- 16094723
TI  - Expression of interferon inducible protein-10 in pancreas of mice.
AB  - AIM: To investigate the expression of interferon inducible protein-10 (IP-10) in
      pancreas of mice and to discuss its possible role in the pathogenesis of type 1
      diabetes. METHODS: Non-obese diabetic (NOD) mice were used as experiment group
      and BALB/c mice as non-diabetic prone model. Immunohistochemistry method was used
      to evaluate the expression of IP-10 in the pancreas of NOD mice and BALB/c mice.
      Immunoelectron microscope was used to show the location of IP-10 in pancreatic
      islet beta cells. RESULTS: Pancreatic islets were positively stained in all the
      NOD mice. Insulitis could be found in mice at the age of 4 wk. The weakly
      positive results were found in control group with no insulitis. Immunoelectron
      microscopy further demonstrated that IP-10 was produced by pancreatic beta cells
      and stored in cytoplasm of the cells. CONCLUSION: IP-10 can be largely produced
      in pancreatic islets of NOD mice at the age of 2 wk when there is no significant
      insulitis, and may play an important part in the pathogenesis of type 1 diabetes
      by attracting immune cells to infiltrate the pancreatic islets.

PMID- 16094724
TI  - Influence of HLA-DRB1 alleles and HBV genotypes on interferon-alpha therapy for
      chronic hepatitis B.
AB  - AIM: To investigate the influence of HLA-DRB(1) alleles and HBV genotypes on
      interferon-alpha therapy for chronic hepatitis B. METHODS: HLA-DRB1*03, *07, *09,
      *12, *15 alleles were determined using polymerase chain reaction/sequence
      specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and
      76 normal control subjects in Shandong Province, and HBV genotypes were
      determined by nested-PCR analysis using type-specific primers in 126 patients.
      RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was
      significantly higher than that in normal control group (chi(2) = 6.33, P<0.025,
      RR = 2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype
      C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%), genotypes D-F were not
      found. Among the 46 DRB1*07(+) patients, 7 were responders and 39 were non
      responders among them (chi(2) = 6.71, P<0.05). The positivity of HLA-DRB1*07 and
      prevalence of HBV genotype C were significantly higher in non-responders than in
      responders. CONCLUSION: High positivities of HLA-DRB1 *07 allele and HBV genotype
      C are closely associated with the lower response to interferon-alpha therapy for
      chronic hepatitis B.

PMID- 16094725
TI  - Hepatotoxicity of NONI juice: report of two cases.
AB  - NONI juice (Morinda citrifolia) is an increasingly popular wellness drink claimed
      to be beneficial for many illnesses. No overt toxicity has been reported to date.
      We present two cases of novel hepatotoxicity of NONI juice. Causality of liver
      injury by NONI juice was asses-sed. Routine laboratory tests and transjugular or
      percutaneous liver biopsy were performed. The first patient underwent successful
      liver transplantation while the second patient recovered spontaneously after
      cessation of NONI juice. A 29-year-old man with previous toxic hepatitis
      associated with small doses of paracetamol developed sub-acute hepatic failure
      following consumption of 1.5 L NONI juice over 3 wk necessitating urgent liver
      transplantation. A 62-year-old woman without evidence of previous liver disease
      developed an episode of self-limited acute hepatitis following consumption of 2 L
      NONI juice for over 3 mo. The most likely hepatotoxic components of Morinda
      citrifolia were anthraquinones. Physicians should be aware of potential
      hepatotoxicity of NONI juice.

PMID- 16094726
TI  - Giant appendiceal mucocele: report of a case and brief review.
AB  - Mucocele of the appendix is a rare lesion, characterized by distension of the
      lumen due to accumulation of mucoid substance. This disease is often asymptomatic
      and pre-operative diagnosis is rare. If untreated, one type of mucocele may
      rupture producing a potentially fatal entity known as pseudomyxoma peritonei. The
      type of surgical treatment is related to the dimensions and to histology of the
      mucocele. Appendectomy is used for simple mucocele or for cystadenoma. Right hemi
      colectomy is recommended for cystadenocarcinoma. In this paper, we report a case
      of a 51-year-old woman with a mobile, painless mass in the right lower quadrant
      of abdomen caused by a giant appendiceal mucocele. Imaging showed a large,
      tubular, cystic structure extending below from the inferior wall of the cecum.
      Surgery revealed a giant retro-cecal appendix measuring 17 cm in length and 4 cm
      in diameter. The final pathologic diagnosis was mucocele caused by mucinous
      cystadenoma.

PMID- 16094727
TI  - Biloma following repeated transcatheter arterial embolization and complicated by
      intrahepatic duct stones: a case report.
AB  - Biloma is an encapsulated bile collection outside the biliary tree due to a bile
      leak. It is occasionally found following traumatic liver injury or iatrogenic
      injury to the biliary tract, induced either during an endoscopic or surgical
      procedure. It is a rare complication of transcatheter arterial embolization
      (TAE). Although biloma can be shrunk by appropriate aspiration or drainage in
      majority of cases, we report a case of intrahepatic biloma following repeated TAE
      for hepatocellular carcinoma (HCC) and complicated by infection and intrahepatic
      stones. This particular constellation of problems has not been reported before
      and the intrahepatic stones need to be removed by percutaneous procedure.

PMID- 16094728
TI  - Acute pancreatitis as an initial symptom of systemic lupus erythematosus: a case
      report and review of the literature.
AB  - Acute pancreatitis as an initial symptom of systemic lupus erythematosus (SLE) is
      rare. We present a report of a 46-year-old female patient who had fever,
      abdominal pain and vomiting, elevated pancreatic enzyme levels, hypocalcemia,
      hypoxemia, and various other laboratory abnormalities. She was first diagnosed
      with acute severe pancreatitis and then with SLE after further investigations.
      After a 2-mo treatment with somatostatin, the patient recovered.

PMID- 16094729
TI  - Two cheers for G8.

PMID- 16094731
TI  - Microbiologist tries to set the record straight.

PMID- 16094730
TI  - Protein kinase activity of phosphoinositide 3-kinase regulates beta-adrenergic
      receptor endocytosis.
AB  - Phosphoinositide 3-kinase (PI(3)K) is a unique enzyme characterized by both lipid
      and protein kinase activities. Here, we demonstrate a requirement for the protein
      kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR)
      internalization. Using PI(3)K mutants with either protein or lipid
      phosphorylation activity, we identify the cytoskeletal protein non-muscle
      tropomyosin as a substrate of PI(3)K, which is phosphorylated in a wortmannin
      sensitive manner on residue Ser 61. A constitutively dephosphorylated (S61A)
      tropomyosin mutant blocks agonist-dependent betaAR internalization, whereas a
      tropomyosin mutant that mimics constitutive phosphorylation (S61D) complements
      the PI(3)K mutant, with only lipid phosphorylation activity reversing the
      defective betaAR internalization. Notably, knocking down endogenous tropomyosin
      expression using siRNAs that target different regions if tropomyosin resulted in
      complete inhibition of betaAR endocytosis, showing that non-muscle tropomyosin is
      essential for agonist-mediated receptor internalization. These studies
      demonstrate a previously unknown role for the protein phosphorylation activity of
      PI(3)K in betaAR internalization and identify non-muscle tropomyosin as a
      cellular substrate for protein kinase activity of PI(3)K.

PMID- 16094732
TI  - African conference highlights gaps in vaccination.

PMID- 16094733
TI  - Gates injects global health research with 437 million dollars.

PMID- 16094734
TI  - New antibiotic approved for MRSA.

PMID- 16094735
TI  - Sexual transmission propels China's HIV epidemic.

PMID- 16094736
TI  - New tuberculosis drug enters human trials.

PMID- 16094738
TI  - A randomised comparison of radical radiotherapy with or without chemotherapy for
      patients with non-small lung cancer: results from the Big Lung Trial.
AB  - BACKGROUND: A meta-analysis of trials comparing primary treatment with or without
      chemotherapy for patients with non-small cell lung cancer published in 1995
      suggested a survival benefit for cisplatin-based chemotherapy in each of the
      primary treatment settings studied, but it included many small trials, and trials
      with differing eligibility criteria and chemotherapy regimens. METHODS: The Big
      Lung Trial was a large pragmatic trial designed to confirm the survival benefits
      seen in the meta-analysis, and this paper reports the findings in the radical
      radiotherapy setting. The trial closed before the required sample size was
      achieved due to slow accrual, with a total of 288 patients randomised to receive
      radical radiotherapy alone (146 patients) or sequential radical radiotherapy and
      cisplatin-based chemotherapy (142 patients). RESULTS: There was no evidence that
      patients allocated sequential chemotherapy and radical radiotherapy had a better
      survival than those allocated radical radiotherapy alone, HR 1.07 (95% CI 0.84
      1.38, P=0.57), median survival 13.0 months for the sequential group and 13.2 for
      the radical radiotherapy alone group. In addition, exploratory analyses could not
      identify any subgroup that might benefit more or less from chemotherapy.
      CONCLUSIONS: Despite not suggesting a survival benefit for the sequential
      addition of chemotherapy to radical radiotherapy, possibly because of the
      relatively small sample size and consequently wide confidence intervals, the
      results can still be regarded as consistent with the meta-analysis, and other
      similarly designed recently published large trials. Combining all these results
      suggests there may be a small median survival benefit with chemotherapy of
      between 2 and 8 weeks.

PMID- 16094739
TI  - Immediate or delayed radiotherapy in advanced non-small cell lung cancer (NSCLC)?
      Data from a prospective randomised study.
AB  - BACKGROUND AND PURPOSE: To compare the course of symptoms and health-related
      quality-of-life (HRQOL) after immediate thoracic radiotherapy (TRT) between
      symptomatic (S) and non-symptomatic (NS) patients with advanced NSCLC. PATIENTS
      AND METHODS: 407 stage III/IV patients were initially treated with immediate TRT
      within a randomised phase III trial comparing different fractionation schedules.
      At inclusion, patients were prospectively stratified according to presence (S) or
      absence (NS) of tumour-related chest/airway symptoms to facilitate comparison
      between these groups. The EORTC QLQ-C30 and LC-13 were used for symptom and HRQOL
      assessments at baseline and at regular intervals up to 1 year (N=395). RESULTS:
      NS patients had significantly more favourable baseline characteristics when
      compared to S patients with a median survival of 11.8 versus 6.0 months
      (P<0.0001), respectively. At baseline, S patients demonstrated HRQOL scores
      inferior to those of NS patients (P<0.01) for most scales. Until week 14, NS
      patients developed more symptoms while S patients experienced symptom relief in
      most scales. After week 14, no significant differences could be observed between
      the groups. CONCLUSION: This study indicates that immediate TRT, given to
      patients with minimal/none chest symptoms, does not prevent development of
      disease-related symptoms and diminished HRQOL. A wait-and-see policy appears to
      be acceptable.

PMID- 16094740
TI  - Massive attack.

PMID- 16094741
TI  - HIV landmark for US.

PMID- 16094742
TI  - Joint meeting of the Experimental Contact Dermatitis Research Group and the
      American Contact Dermatitis Society. October 28-30, 2004, Bethesda, Maryland,
      USA.

PMID- 16094743
TI  - Current Issues in HIV Management and the 3rd European Stavudine Symposium.
      Conference proceedings. March 1999, Cannes, France.

PMID- 16094744
TI  - Issue in honor of Vladimir Petrovich Skulachev.

PMID- 16094745
TI  - The latest waves in calcium signaling.
AB  - Ca2+ is a universal second messenger that is a key component of myriad processes
      in all cell types. Perturbations in normal intracellular Ca2+ concentrations
      underlie many common pathological conditions, ranging from cardiac hypertrophy to
      ischemic death of neurons. A recent meeting addressed the contributions of Ca2+
      and Ca2+ binding proteins to health and disease. Insights gleaned from
      mechanistic studies offered the potential for new therapeutic approaches to
      combat a variety of diseases resulting from alterations in Ca2+ homeostasis.

PMID- 16094746
TI  - Abstracts of the 24th Congress of the Society of Biomechanics. Beaune, France, 15
      17 September 1999.

PMID- 16094747
TI  - Abstracts of the 8th AAOMS Annual Meeting, September 20-24, 2005, Boston,
      Massachusetts, USA.

PMID- 16094748
TI  - Abstracts of the SOGC (Society of Obstetricians and Gynaecologists of Canada)
      61st Annual Clinical Meeting, June 16-21, 2005, Quebec City, Canada.

PMID- 16094749
TI  - Abstracts of the 20th International Symposium on Neurogastroenterology and
      Motility, Toulouse, France, 3-6 July 2005.

PMID- 16094750
TI  - The cost of insurance.

PMID- 16094751
TI  - High-grade cervical dysplasias: to regress or not to regress?

PMID- 16094752
TI  - Sleeping beauty offers new method to find cancer genes.

PMID- 16094753
TI  - Photodynamic therapy for bladder cancer.

PMID- 16094754
TI  - Proteasome inhibitor for treatment of multiple myeloma.

PMID- 16094755
TI  - Radiotherapy after mastectomy more common in men.

PMID- 16094756
TI  - Salivary bacteria linked to oral cancers.

PMID- 16094757
TI  - New thinking on epithelial proliferation in colon cancer.

PMID- 16094758
TI  - Pemetrexed combination improves mesothelioma survival.

PMID- 16094759
TI  - Model predicts age of ovarian failure in patients with cancer.

PMID- 16094760
TI  - Unique features of inflammatory breast carcinoma.

PMID- 16094761
TI  - West Nile virus activity--United States, 2005.

PMID- 16094762
TI  - Amiodarone versus sotalol for atrial fibrillation.

PMID- 16094763
TI  - Amiodarone versus sotalol for atrial fibrillation.

PMID- 16094764
TI  - Amiodarone versus sotalol for atrial fibrillation.

PMID- 16094765
TI  - Multidetector-row computed tomography in suspected pulmonary embolism.

PMID- 16094766
TI  - Detection of acute HIV infections.

PMID- 16094767
TI  - Traumatic brain injury in the war zone.

PMID- 16094768
TI  - Medical study: aspiring parents, genotypes and phenotypes: the unexamined myth of
      the perfect baby.
AB  - Although many have argued that assisted reproductive technologies ("ARTs")
      attract those with a desire to genetically engineer their offspring, this claim
      has yet to be verified. To address this question, we surveyed three groups: the
      general public, people enrolling in an in vitro fertilization ("IVF") program,
      and pregnant couples. We asked subject which traits they would select in their
      children if it were possible to use a magic wand to do so and to value genetic
      relatedness. In our sample, the potential parents who were using ARTs were less
      likely to express a desire to select traits in their offspring than were the
      general public, and just as likely as the pregnant couples, Those using ARTs ,
      however, place greater importance on having genetically related children than the
      others. Thus, the widely held view that reproductive technology is utilized by
      those most likely to favor genetic engineering is falsified by out findings.

PMID- 16094769
TI  - Teriparatide, osteoporosis, calcium, and vitamin D.

PMID- 16094770
TI  - Carcinogenicity of combined oestrogen-progestagen contraceptives and menopausal
      treatment.

PMID- 16094771
TI  - Reflections on historical, scientific, and legal issues relevant to designing
      approval pathways for generic versions of recombinant protein-based therapeutics
      and monoclonal antibodies.

PMID- 16094772
TI  - Aronow's "Should the NCEP III guidelines be changed in elderly and younger
      persons at high risk for cardiovascular events?" Commentary.

PMID- 16094773
TI  - The Prescription Drug User Fee Act: is a faster Food and Drug Administration
      always a better Food and Drug Administration?

PMID- 16094774
TI  - Aronow's "Should the NCEP III guidelines be changed in elderly and younger
      persons at high risk for cardiovascular events?" Commentary.

PMID- 16094775
TI  - Proton therapy analysis using the Monte Carlo method.
AB  - The range and straggling data obtained from the transport of ions in matter
      (TRIM) computer program were used to determine the trajectories of monoenergetic
      60 MeV protons in muscle tissue by using the Monte Carlo technique. The
      appropriate profile for the shape of a proton pencil beam in proton therapy as
      well as the dose deposited in the tissue were computed. The good agreements
      between our results as compared with the corresponding experimental values are
      presented here to show the reliability of our Monte Carlo method.

PMID- 16094776
TI  - Nuclear fragmentation cross-sections of 400 A MeV 36Ar and 40Ar in collisions
      with light and heavy target nuclei.
AB  - We have measured fragmentation cross-sections of Ar projectile nuclei at beam
      energy of 400 A MeV using experimental set-ups with plastic nuclear track
      detectors and different targets. In this paper total charge changing cross
      sections and elemental fragmentation cross-sections for the production of
      fragments with charges ZF > or = 7 in interactions with H, C, Al, Cu, Ag and Pb
      target nuclei are presented. The dependence of the cross-sections on the fragment
      charge number and target charge number are discussed. The experimental results
      are compared to predictions of semi empirical cross-section models.

PMID- 16094777
TI  - Some more new etchants for CR-39 detector.
AB  - Recently, several new etchants have been reported for CR-39 detector (Molten
      Ba(OH)2. 8H2O as an etchant for CR-39 detector, Radiat. Meas. 37 (2003) 205;
      Discovery of new etchants for CR-39 detector, Radiat. Meas. (2004)). We have made
      further progress in this direction and have unveiled two more new etchants which
      are reported in this article. CR-39 detectors were irradiated with fission
      fragments and alpha particles from a thin 252Cf disc source. The irradiated
      detectors were then etched in our newly introduced etching solutions as well as
      in conventionally used 6 M NaOH aqueous solution at 70 degrees C. The newly
      prepared etching solutions included NaOH dissolved in methanol and NaOH dissolved
      in methanol + water. Optimum values of NaOH concentration in methanol as well as
      in methanol + water were determined. Optimum etching temperatures were also
      determined for both the above-mentioned etchants. From fission and alpha track
      diameters, bulk etching rate (VB), track etching rate (VT) and etching efficiency
      (eta) were determined and compared with that obtained for 6 M NaOH at 70 degrees
      C. Both the newly introduced etchants were found more efficient than the
      conventionally used 6 M aqueous NaOH (64%) at 70 degrees C and have relatively
      much smaller etching time.

PMID- 16094778
TI  - A computer-based procedure for assessing functional cognitive skills in patients
      with neurological injuries: the virtual street.
AB  - PRIMARY OBJECTIVE: The aim of the present investigation was to construct and
      pilot test a computer-based multi-tasking procedure that could be used to assess
      the ability of patients with neurological damage to remember instructions in the
      real world. RESEARCH DESIGN: A simulated street scene was constructed from a
      network of photographs and sounds that patients could move through using a touch
      screen. Three patients with severe, moderate or mild cognitive impairment were
      assessed on a range of neuropsychological tests and three multi-tasking
      procedures based in the street. The performance of each patient was compared with
      that of a matched control. PROCEDURE: Three tests were administered, each of
      which involved 'walking' along the length of the street once. On the first test,
      participants were given up to five errands to remember while moving along the
      street. On the other two tests they were given three instructions to carry out
      repeatedly (e.g. 'Record the name of the nearest shop when you hear a dog bark').
      In one condition they were given the three instructions on a sheet they could
      consult and in the other they had no list. OUTCOMES AND RESULTS: In each case the
      patient performed more poorly on the multi-tasking test than the matched control.
      The patients' performance on the computer-based tests was consistent with
      clinical descriptions of their memory-related deficits. CONCLUSION: The results
      illustrate the way in which computer presentation of naturalistic stimuli can be
      used to construct flexible and standardized tests of memory functioning that have
      enhanced ecological validity.

PMID- 16094779
TI  - Constraint-induced therapy for moderate chronic upper extremity impairment after
      stroke.
AB  - PRIMARY OBJECTIVE: To explore the effectiveness of constraint-induced therapy
      (CIT) in the treatment of individuals with moderate chronic upper extremity
      paresis. RESEARCH DESIGN: Multiple case reports, pre-post-treatment comparisons
      as well as long-term follow-ups at 1 and 6 months after intervention. METHODS AND
      PROCEDURES: Seven subjects, each greater than 12 months post-stroke, participated
      in an intensive 3 weeks CIT programme. The Wolf Motor Function Test (WMFT), Motor
      Activity Log (MAL) and Fugl-Meyer Evaluation (FM) were used to measure outcomes.
      MAIN OUTCOMES AND RESULTS: Subjects exhibited notable improvements in mean WMFT
      scores (0.25 point increase post-treatment, 0.38 point increase at 1-month follow
      up, 0.44 point increase at 6-month follow-up). Similarly, improvements were seen
      for mean MAL (1.71 points for AS, 1.77 points for HW) and FM scores (6 points FM
      UE, 6 points FM-TOT) post-treatment. Additional improvements were seen at some
      follow-up assessments. CONCLUSIONS: Subjects demonstrated gains in objective
      measures, however, did not regain normal functional ability of their paretic
      upper extremities. Further investigation of the effects of CIT in this
      population, as well the functional significance of the objective measures used is
      warranted.

PMID- 16094780
TI  - Botulinum toxin type A in the treatment of children and adolescents with an
      acquired brain injury.
AB  - PRIMARY OBJECTIVE: To describe clinical experience using botulinum toxin type A
      (BTX-A) in children with acquired brain injury. RESEARCH DESIGN: Single centre,
      open label, pilot study. METHODS AND PROCEDURES: Twenty-one patients were
      randomized to three groups according to impairment severity and treatment
      objectives. EXPERIMENTAL INTERVENTIONS: Group 1: Spastic quadriparesis patients
      with impaired consciousness treated with the primary goal of improving comfort
      and well-being; Group 2: Patients with upper limb spasticity treated with the
      primary goal of improving arm functioning; Group 3: Lower limb spasticity
      patients treated with the primary goal of improving leg function. OUTCOMES AND
      RESULTS: Baseline, 1, 3 and 5-month post-treatment assessments were carried out
      using joint goniometry, Modified Ashworth Scale and video-observations. All
      groups demonstrated initial improvements, with patients in Group 2 showing a
      positive effect at least 5 months post-treatment. CONCLUSIONS: With a good
      outlining of treatment goals, BTX-A is an effective therapy for brain injury
      patients.

PMID- 16094781
TI  - Cognitive structure of executive deficits in patients with frontal lesions
      performing activities of daily living.
AB  - OBJECTIVE: Executive function in activities of daily living (ADL) were
      investigated in 10 patients with excised frontal lobe tumours. METHOD: The
      patients with frontal lesions were compared to 10 normal controls with a
      neuropsychological test battery, a script generation task and a realistic
      implementation of complex multi-task ADL (planning and preparing a meal).
      RESULTS: The patients manifested numerous basic executive deficits on the paper
      pencil tests, were unimpaired on the script generation task despite an aberrant
      semantic structure and manifested marked anomalies in the meal preparation task.
      CONCLUSION: Frontal lobe deficits in lengthy complex multi-task ADL can be
      explained by impairment of several executive functions, generalized slowness of
      performance and paucity of behaviour.

PMID- 16094782
TI  - Anterior hypopituitarism following traumatic brain injury.
AB  - PRIMARY OBJECTIVES: To review evidence that there exists a substantial sub
      population of patients with endocrine disorders as a result of traumatic brain
      injury (TBI) and to underscore the importance of screening patients with TBI
      considered most at risk for hypopituitarism with the goal of attaining beneficial
      effects in terms of morbidity and quality of life. DESIGN AND METHODS: Reviewed
      recent literature regarding the frequency of TBI-induced hypopituitarism. MAIN
      OUTCOMES AND RESULTS: Studies by Kelly DF, Gaw Gonzalo IT, Cohan P, et al.
      Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid
      hemorrhage: A preliminary report. Journal of Neurosurgery 2000;93:743-751,
      Lieberman SA, Oberoi AL, Gilkison CR, et al. Prevalence of neuroendocrine
      dysfunction in patients recovering from traumatic brain injury. Journal of
      Clinical Endocrinology and Metabolism 2001;86:2752-2756 and Aimaretti G, Ambrosio
      MR, Di Somma C, et al. Traumatic brain injury and subarachnoid haemorrhage are
      conditions at high risk for hypopituitarism. Screening study at 3 months after
      the brain injury, In press., found that about one-half to one-third of patients
      with TBI had anterior pituitary hormone deficiencies, including growth hormone
      (GH) deficiency in 15-21%, and subtle deficiencies in thyroid, adrenal and
      gonadal axes. One or more hormonal deficiencies produce diverse physical and
      psychological symptoms that may mimic symptoms attributed to brain trauma and may
      impair rehabilitation. A more general concern is the fact that hypopituitarism
      increases the risk of significant morbidity (e.g. ischaemic heart disease) and
      mortality (shortened life span). CONCLUSIONS: To attain maximal improvement in
      mental and physical functioning as well as in quality of life for victims of TBI,
      it is crucial that anterior pituitary hormonal function be assessed. Appropriate
      hormone replacement therapy for those patients with both TBI and TBI-induced
      pituitary function impairment could, for the first time, allow treatment and
      correction of underlying causes of TBI sequelae rather than merely symptomatic
      treatment.

PMID- 16094783
TI  - Efficacy of early use of intrathecal baclofen therapy for treating spastic
      hypertonia due to acquired brain injury.
AB  - OBJECTIVE: To determine the efficacy and safety of early (<1 year post-disease
      onset) use of intrathecal baclofen (ITB). DESIGN: Consecutive case series of 14
      individuals with spastic hypertonia due to trauma (5), anoxia (6) and stroke (3).
      MAIN OUTCOME MEASURES: Modified Ashworth (MAS) and Disability Rating (DRS)
      scales. INTERVENTIONS: ITB pump placement within 1 year of onset, after
      inadequate response to other previous treatment modalities. RESULTS: At follow-up
      after ITB pump implantation (mean = 13.9 months; mean daily dose = 591.5 microg
      per day), mean MAS scores improved from baseline by 1.0 and 2.1 points in the
      upper and lower limbs, respectively. DRS scores did not change significantly.
      Functional gains included decreased pain and improved gait speed and motor
      skills. The only complication was spinal leak in one subject. CONCLUSIONS: ITB
      therapy within 1 year of onset of acquired brain injury appears effective and
      safe in decreasing spastic hypertonia and does not appear to adversely affect
      recovery.

PMID- 16094784
TI  - Antecedent interventions in the management of maladaptive behaviours in a child
      with brain injury.
AB  - Typically behaviour management plans attempt to change behaviour by manipulating
      the environmental consequences of selected behaviour. However, identifying the
      antecedent events that precede behaviour has also been demonstrated to be an
      important component of effective behaviour change programmes. The present case
      presentation attempts to demonstrate how antecedent procedures could be used to
      effectively manage behaviour problems in individuals with brain injury. Visual
      inspection of changes in the frequency of physical aggression and self-injurious
      behaviour of a child with brain injury provides preliminary data supporting the
      use of an intervention package of antecedent and consequence-based procedures.
      Clinical implications, limitations and possibilities for future research of
      antecedent control procedures are discussed.

PMID- 16094785
TI  - Follow-up of neuropsychological function recovery in a 9-year-old girl with
      anoxic encephalopathy: a window on the brain re-organization processes.
AB  - OBJECTIVE: To investigate comprehensive neuropsychological outcome, disabilities
      in daily life and individual recovery processes in a case of anoxic
      encephalopathy. DESIGN: A 9-year-old child's functional outcome after anoxic coma
      was evaluated in a follow-up study with assessments at 5, 9 and 12 months post
      injury. A comprehensive neuropsychological protocol was administered. Qualitative
      methods of analysis and ecological observation were associated with standard and
      non-standard quantitative measures. RESULTS: The child presented pervasive
      functional deficits with prevalence of gnosic, praxic and self-regulatory
      dysfunction. Dissociated functional recovery was documented in 12 months time.
      Improvement of self-regulatory abilities was likely a 'propeller' of global
      system re-organization. CONCLUSION: A descriptive longitudinal study of
      functional and ecological behavioural changes after anoxic coma provides insight
      into the re-adaptation processes in the brain connected to post-lesion ecological
      and training experiences. Contextual factors and their relations to functional
      improvements deserve further study.

PMID- 16094786
TI  - Teaching for learning and improvement.

PMID- 16094787
TI  - The effect of a metacognitive intervention on approach to and self-regulation of
      learning in baccalaureate nursing students.
AB  - There is little empirical support in the nursing education literature related to
      the process of learning. This quasi-experimental study examined the effect of a
      metacognitive intervention (concept mapping) on approach to learning and self
      regulation of learning in a sample of baccalaureate nursing students. Significant
      group differences were found in the concept mapping group, with an increase in
      deep approach to learning and adaptive control belief mean scores at the end of
      the semester. Students in the control group experienced a decrease in the deep
      approach to learning mean score and an increase in the surface approach to
      learning mean score at the end of the semester. Therefore, students who used
      concept mapping demonstrated an increase in deep approach to learning and the
      self-regulation of that learning, compared with students who did not use concept
      mapping. The results of this study provide empirical support for the use of
      concept mapping as a metacognitive intervention.

PMID- 16094788
TI  - The effect of teaching method on objective test scores: problem-based learning
      versus lecture.
AB  - This study investigated the effect of teaching method on objective test scores of
      students in a school of nursing. The hypothesis stated there was a difference
      between objective test scores of students who were taught content on diabetes
      using problem-based learning (PBL) and students taught the same content using the
      traditional lecture method. Junior nursing students enrolled in the Adult Health
      I nursing course in the fall of 2001 were taught the diabetes content using
      lecture as the teaching method, while students enrolled in the same course in the
      spring of 2002 were taught the same content using PBL. A pretest and posttest
      were administered to both groups of students. Both the pretest and posttest
      scores of the two groups were compared using an independent t test, and no
      statistically significant difference was found in the scores of the two groups.
      The results of this study support the null hypothesis: that there is no
      difference in objective test scores based on teaching method (lecture versus
      PBL).

PMID- 16094789
TI  - The effect of classroom simulation on nursing students' self-efficacy related to
      health teaching.
AB  - The purpose of this descriptive study was to investigate the effect of classroom
      simulation on third-year baccalaureate nursing students' self-efficacy in health
      teaching. Bandura's self-efficacy model provided the conceptual framework. A
      nonprobability, convenience sample of 22 students completed the self-efficacy
      questionnaire before and after the simulation workshop sessions. Students'
      overall self-efficacy scores increased significantly (p = 0.001) following the
      two sessions of role-playing case studies, suggesting more perceived confidence
      in performing health teaching. Recommendations include continuing the use of
      simulation as a teaching-learning method, applying simulation as a strategy to
      enhance other learner behaviors, and cultivating faculty's use of simulation in
      their teaching.

PMID- 16094790
TI  - Using dimensional analysis to improve drug dosage calculation ability.
AB  - Confidence and accuracy in medication calculation ability continue to be
      problematic among nursing students. This deficiency has been attributed to poor
      basic mathematical skills, inconsistent teaching methods, and inconsistent or
      incorrect use of multiple mathematical formulas. This article provides evidence
      of the value of dimensional analysis as an effective teaching strategy for
      calculating drug dosages.

PMID- 16094791
TI  - A comparison of teaching strategies: lecture notes combined with structured group
      discussion versus lecture only.
AB  - In this study, we compared two teaching strategies: lecture notes combined with
      structured group discussion versus lecture only. We sought to help nurse
      educators identify the most effective teaching strategies for nursing students.
      We compared the examination scores of two groups of students who took a 3-credit
      medical-surgical nursing course. The control group (N = 88) received lecture only
      as the teaching method, whereas the experimental group (N = 81) received word
      processed lecture notes along with structured group discussion. A one-tailed,
      independent sample t test was used to compare the mean examination scores of the
      two groups. The chi-square test was used to determine whether a significant
      difference existed between the course-passing rates of the two groups. The
      results showed a statistically significant difference between the means of the
      experimental and control groups. However, no statistically significant difference
      existed between the course-passing rate of students in the experimental group and
      that of students in the control group. These results provide strong support for
      the use of lecture notes in conjunction with structured group discussion as a
      teaching strategy. We recommend replicating this study using samples from other
      courses, and conducting further studies that include students' NCLEX-RN results
      as a third dependent variable.

PMID- 16094792
TI  - Collaboration with city agencies: a winning approach to community assessment.
AB  - Five graduate nursing students made a difference in the health of San Antonio
      citizens by conducting a community assessment as part of a standard clinical
      activity in their community health nursing course. The students and their
      professor were able to effect city-wide change for health protection and
      promotion through collaboration with the City of San Antonio Planning Department
      (CSAPD). By compiling information, linking organizations, and speaking before
      community groups about the importance of a fluoridated water supply, the students
      generated public interest and momentum, which resulted in a successful vote to
      add fluoride to the water supply. In addition, they were able to add to the
      assessment compiled by the Planning Department employees and increase the CSAPD's
      awareness of health concerns as an important area to assess within a community.
      The resulting assessment was more comprehensive than it would have been without
      the students' input. This use of collaboration provides a model other faculty may
      adopt for community assessment.

PMID- 16094793
TI  - Quality handout development and use.
AB  - Handouts have been a mainstay of teaching for many years. Even as content moves
      to electronic delivery and dissemination, well-crafted handouts are often printed
      for future use. In this article, we examine appropriate handout use and provide
      specific guidelines for improving handout quality. A section focused on
      professional elements important during handout construction emphasizes the
      creation of handouts that become more functional, so they can be used outside of
      the classroom experience.

PMID- 16094794
TI  - Lowering stress while teaching research: a creative arts intervention in the
      classroom.
AB  - Undergraduate students often request "hands-on" research experience but seldom
      have the time and opportunity during a one-semester introductory course to
      participate in such a project. The purposes of this educational approach,
      implemented during a beginning research class for baccalaureate nursing students,
      were to provide an opportunity for students to participate in an experimental
      research study, and test the effect of a creative arts intervention on students'
      stress, anxiety, and emotions. Students designed, participated in, and analyzed
      the results of the project. The intervention significantly reduced stress and
      anxiety and increased positive emotions in this student population, while
      providing a creative research experience. For future use, the intervention may be
      helpful with a variety of vulnerable groups.

PMID- 16094795
TI  - Blending aesthetics and empirics: teaching health assessment in an art gallery.
AB  - An art gallery was used successfully as a clinical laboratory for nursing
      students studying health assessment. Art galleries provide students with a
      visually rich and stimulating environment that can support the development of
      astute visual inspection skills. Working in pairs, students examined artwork
      incorporating design elements common to both physical assessment and artistic
      inquiry. Students described new learning and clinical application through this
      innovative laboratory experience. Uniting traditionally empirical coursework with
      an aesthetic learning opportunity is important in the development of caring,
      humanistic professionals.

PMID- 16094796
TI  - Using games as a teaching strategy.
AB  - Both of these games are relatively easy to develop and are fun ways for faculty
      to challenge students and provide immediate feedback so students can assess their
      own comprehension and, consequently, their need for further study (Ulrich &
      Glendon, 2005). Teacher-delivered factual material is often tedious and boring,
      while games are highly motivating and accomplish the same objectives.

PMID- 16094797
TI  - Integrating an exercise on mass casualty response into the curriculum.

PMID- 16094798
TI  - Using humor to teach postpartum topics.
AB  - I have found that these two hands-on activities--demonstration and return
      demonstration, and roleplaying of a postpartum woman--help promote learning in a
      relaxed environment.

PMID- 16094799
TI  - Prevention of ventilator-associated pneumonia shows how small improvements can
      help provide high-quality care.
AB  - Ventilator-associated pneumonia (VAP) is one of the top causes of morbidity and
      mortality in hospital intensive care units. But new strategies are emerging
      including the use of "ventilator bundles"-to help hospitals push the rate of VAP
      down to zero. Lessons can be learned about stopping VAP morbidity and mortality
      that may provide useful strategies in other clinical areas outside the ICU.

PMID- 16094800
TI  - New study shows progress for Medicare quality of care.
AB  - A new 60-chart report prepared for the Commonwealth Fund on the health of
      Medicare beneficiaries shows many signs of progress-especially in areas that have
      been targeted as national priorities such as mammography, inpatient treatment of
      heart attacks, and outpatient care of diabetes. However, noticeable gaps and
      deficiencies in care, along with great variations in healthcare quality, still
      exist nationwide.

PMID- 16094801
TI  - Joint Commission International Center for Patient Safety offers new web site.

PMID- 16094802
TI  - Updated Primary Stroke Center Certification appendix for the disease-specific
      care manual.

PMID- 16094803
TI  - The functions of societies and the evolution of group living: spider societies as
      a test case.
AB  - Many models have been advanced to suggest how different expressions of sociality
      have evolved and are maintained. However these models ignore the function of
      groups for the particular species in question. Here we present a new perspective
      on sociality where the function of the group takes a central role. We argue that
      sociality may have primarily a reproductive, protective, or foraging function,
      depending on whether it enhances the reproductive, protective or foraging aspect
      of the animal's life (sociality may serve a mixture of these functions).
      Different functions can potentially cause the development of the same social
      behaviour. By identifying which function influences a particular social behaviour
      we can determine how that social behaviour will change with changing conditions,
      and which models are most pertinent. To test our approach we examined spider
      sociality, which has often been seen as the poor cousin to insect sociality. By
      using our approach we found that the group characteristics of eusocial insects is
      largely governed by the reproductive function of their groups, while the group
      characteristics of social spiders is largely governed by the foraging function of
      the group. This means that models relevant to insects may not be relevant to
      spiders. It also explains why eusocial insects have developed a strict caste
      system while spider societies are more egalitarian. We also used our approach to
      explain the differences between different types of spider groups. For example,
      differences in the characteristics of colonial and kleptoparasitic groups can be
      explained by differences in foraging methods, while differences between colonial
      and cooperative spiders can be explained by the role of the reproductive function
      in the formation of cooperative spider groups. Although the interactions within
      cooperative spider colonies are largely those of a foraging society, demographic
      traits and colony dynamics are strongly influenced by the reproductive function.
      We argue that functional explanations help to understand the social structure of
      spider groups and therefore the evolutionary potential for speciation in social
      spiders.

PMID- 16094804
TI  - Sexual selection research on spiders: progress and biases.
AB  - The renaissance of interest in sexual selection during the last decades has
      fuelled an extraordinary increase of scientific papers on the subject in spiders.
      Research has focused both on the process of sexual selection itself, for example
      on the signals and various modalities involved, and on the patterns, that is the
      outcome of mate choice and competition depending on certain parameters. Sexual
      selection has most clearly been demonstrated in cases involving visual and
      acoustical signals but most spiders are myopic and mute, relying rather on
      vibrations, chemical and tactile stimuli. This review argues that research has
      been biased towards modalities that are relatively easily accessible to the human
      observer. Circumstantial and comparative evidence indicates that sexual selection
      working via substrate-borne vibrations and tactile as well as chemical stimuli
      may be common and widespread in spiders. Pattern-oriented research has focused on
      several phenomena for which spiders offer excellent model objects, like sexual
      size dimorphism, nuptial feeding, sexual cannibalism, and sperm competition. The
      accumulating evidence argues for a highly complex set of explanations for
      seemingly uniform patterns like size dimorphism and sexual cannibalism. Sexual
      selection appears involved as well as natural selection and mechanisms that are
      adaptive in other contexts only. Sperm competition has resulted in a plethora of
      morphological and behavioural adaptations, and simplistic models like those
      linking reproductive morphology with behaviour and sperm priority patterns in a
      straightforward way are being replaced by complex models involving an array of
      parameters. Male mating costs are increasingly being documented in spiders, and
      sexual selection by male mate choice is discussed as a potential result. Research
      on sexual selection in spiders has come a long way since Darwin, whose spider
      examples are reanalysed in the context of contemporary knowledge, but the same
      biases and methodological constraints have persisted almost unchanged through the
      current boom of research.

PMID- 16094805
TI  - Complex interactions among mammalian carnivores in Australia, and their
      implications for wildlife management.
AB  - Mammalian carnivore populations are often intensively managed, either because the
      carnivore in question is endangered, or because it is viewed as a pest and is
      subjected to control measures, or both. Most management programmes treat
      carnivore species in isolation. However, there is a large and emerging body of
      evidence to demonstrate that populations of different carnivores interact with
      each other in a variety of complex ways. Thus, the removal or introduction of
      predators to or from a system can often affect other species in ways that are
      difficult to predict. Wildlife managers must consider such interactions when
      planning predator control programmes. Integrated predator control will require a
      greater understanding of the complex relationships between species. In many parts
      of the world, sympatric species of carnivores have coexisted over an evolutionary
      time scale so that niche differentiation has occurred, and competition is
      difficult to observe. Australia has experienced numerous introductions during the
      past 200 years, including those of the red fox (Vulpes vulpes) and the feral cat
      (Felis catus). These species now exist in sympatry with native mammalian
      predators, providing ecologists with the opportunity to study their interactions
      without the confounding effects of coevolution. Despite an increasing body of
      observational evidence for complex interactions among native and introduced
      predators in Australia, few studies have attempted to clarify these relationships
      experimentally, and the interactions remain largely unacknowledged. A greater
      understanding of these interactions would provide ecologists and wildlife
      managers world-wide with the ability to construct robust predictive models of
      carnivore communities, and to identify their broader effects on ecosystem
      functioning. We suggest that future research should focus on controlled and
      replicated predator removal or addition experiments. The dingo (Canis lupus
      dingo), as a likely keystone species, should be a particular focus of attention.

PMID- 16094806
TI  - Emergent properties from organisms to ecosystems: towards a realistic approach.
AB  - More realistic approaches are needed to understand the complexity of ecological
      systems. Emergent properties of real systems can be used as a basis for a new,
      neither reductionist nor holistic, approach. Three systems, termed here BUBBLEs,
      WAVEs and CRYSTALs, have been identified as exhibiting emergent properties. They
      are non-hierarchical assemblages of individual components, with amplification and
      connectedness being two main principles that govern their build-up, maintenance
      and mutual relationships. Examples from various fields of biological and
      ecological science are referred to, ranging from individual organisms to
      landscapes.

PMID- 16094807
TI  - Pollen and seed dispersal among dispersed plants.
AB  - The ecological significance of spacing among plants in contributing to the
      maintenance of species richness, particularly in tropical forests, has received
      considerable attention that has largely focussed on distance- and density
      dependent seed and seedling mortality. More recently it has become apparent that
      plant spacing is also relevant to pollination, which often constrains seed
      production. While seed and seedling survival is reduced at high conspecific
      densities, pollination success, by contrast, is positively correlated to local
      conspecific density. Distance-dependent mechanisms acting on pollination and seed
      production have now been described for a variety of plants, with relatively
      isolated plants or fragmented populations generally suffering reduced fecundity
      due to pollen limitation. Yet there is considerable variability in the
      vulnerability of plant species to pollination failure, which may be a function of
      breeding system, life history, the pollination vector, the degree of
      specialisation among plants and their pollinators, and other indirect effects of
      habitat change acting on plants or pollinators. As reduced tree densities and
      population fragmentation are common outcomes of anthropogenically altered
      landscapes, understanding how pollination processes are affected in such degraded
      landscapes can inform effective conservation and management of remaining natural
      areas.

PMID- 16094808
TI  - A complete phylogeny of the whales, dolphins and even-toed hoofed mammals
      (Cetartiodactyla).
AB  - Despite the biological and economic importance of the Cetartiodactyla, the
      phylogeny of this clade remains controversial. Using the supertree approach of
      matrix representation with parsimony, we present the first phylogeny to include
      all 290 extant species of the Cetacea (whales and dolphins) and Artiodactyla
      (even-toed hoofed mammals). At the family-level, the supertree is fully resolved.
      For example, the relationships among the Ruminantia appear as (((Cervidae,
      Moschidae) Bovidae) (Giraffidae, Antilocapridae) Tragulidae). However, due to
      either lack of phylogenetic study or contradictory information, polytomies occur
      within the clades Sus, Muntiacus, Cervus, Delphinidae, Ziphiidae and Bovidae.
      Complete species-level phylogenies are necessary for both illustrating and
      analysing biological, geographical and ecological patterns in an evolutionary
      framework. The present species-level tree of the Cetartiodactyla provides the
      first opportunity to examine comparative hypotheses across entirely aquatic and
      terrestrial species within a single mammalian order.

PMID- 16094809
TI  - Primate spermatogenesis: new insights into comparative testicular organisation,
      spermatogenic efficiency and endocrine control.
AB  - Owing to the close phylogenetic relationship of Platyrrhini (New World monkeys)
      and Catarrhini (Old World monkeys) to man, nonhuman primates are often used as
      models for the study of male reproductive physiology and endocrinology. This
      review aims at providing new data and insights into comparative primate
      spermatogenesis, dealing specifically with quantitative aspects of germinal
      epithelial organisation and germ cell production, and with the roles of
      gonadotrophic hormones in this process. Typically, the seminiferous epithelium is
      composed of specific germ cell associations (spermatogenic stages). In rodents,
      prosimians and most Catarrhini, tubular cross sections contain a single
      spermatogenic stage whereas in Platyrrhini, great apes and man multi-stage
      tubules are present. Since Platyrrhini represent a more basal type of primate,
      this spermatogenic feature must have developed convergently. The primate multi
      stage tubular arrangement was previously believed to be associated with low
      spermatogenic efficiency. However, recent studies using new methodological
      approaches and comparing primate species from all taxa have revealed that
      multistage organisation is compatible with highly efficient spermatogenesis. In
      fact, meta-analysis demonstrated that the efficiency of spermatogenesis in
      several nonhuman primate species is comparable to that of rodents which are
      considered as species with highly efficient germ cell production. The duration of
      the spermatogenic process was not related to organisation or efficiency of
      spermatogenesis. Sertoli cell work load was species-specific but had no impact on
      germ cell numbers and on the efficiency of spermatogenesis. The gonadotrophic
      hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH) are the
      primary regulators of primate testicular function. Recent studies revealed that
      in New World monkeys chorionic gonadotrophin (CG)--the primate pregnancy hormone-
      regulates testosterone production instead of LH. Receptor studies demonstrated a
      dual action of the closely related hormones LH and CG in primates. It is
      hypothesised that following the divergence of the Platyrrhini lineage from
      Catarrhini, the LH/CG system evolved independently with ancestral functions of
      the LH/CG system retained in the neotropical taxa. In summary, key spermatogenic
      features are preserved across all primate taxa whereas male reproductive
      endocrinology features appear substantially different in the neotropical primates
      compared to other primate lineages.

PMID- 16094810
TI  - Terrestrial insects along elevation gradients: species and community responses to
      altitude.
AB  - The literature on the response of insect species to the changing environments
      experienced along altitudinal gradients is diverse and widely dispersed. There is
      a growing awareness that such responses may serve as analogues for climate
      warming effects occurring at a particular fixed altitude or latitude over time.
      This review seeks, therefore, to synthesise information on the responses of
      insects and allied groups to increasing altitude and provide a platform for
      future research. It focuses on those functional aspects of insect biology that
      show positive or negative reaction to altitudinal changes but avoids emphasising
      adaptation to high altitude per se. Reactions can be direct, with insect
      characteristics or performance responding to changing environmental parameters,
      or they can be indirect and mediated through the insect's interaction with other
      organisms. These organisms include the host plant in the case of herbivorous
      insects, and also competitor species, specific parasitoids, predators and
      pathogens. The manner in which these various factors individually and
      collectively influence the morphology, behaviour, ecophysiology, growth and
      development, survival, reproduction, and spatial distribution of insect species
      is considered in detail. Resultant patterns in the abundance of individual
      species populations and of community species richness are examined. Attempts are
      made throughout to provide mechanistic explanations of trends and to place each
      topic, where appropriate, into the broader theoretical context by appropriate
      reference to key literature. The paper concludes by considering how montane
      insect species will respond to climate warming.

PMID- 16094811
TI  - Marriage and family therapists and psychotropic medications: practice patterns
      from a national study.
AB  - A national sample of marriage and family therapists (MFTs) was used to describe
      practice patterns of MFTs whose clients use psychotropics and to compare
      medicated and nonmedicated clients. Marriage and Family Therapists (n=283)
      reported on 195 medicated and 483 nonmedicated adult clients. Clients (n=375)
      rated their improvement and satisfaction with treatment. Results showed that 91%
      of MFTs treat medicated clients, and these clients accounted for 25% of MFT
      cases. Medicated clients were most often seen in individual therapy, had more
      serious medical problems, and showed greater cumulative improvement in relational
      functioning. Therapists from MFT educational backgrounds had fewer medicated
      clients than MFTs from other educational backgrounds.

PMID- 16094812
TI  - Toward a standard of care for child ADHD: implications for marriage and family
      therapists.
AB  - In this article, we briefly review the etiology of Attention Deficit
      Hyperactivity Disorder (ADHD) and describe the most current scientifically
      supported theory about the nature of this disorder. Based on the research
      literature, several organizations have established standards of care for its
      diagnosis and treatment, which involves a multimodal strategy for treatment at
      the biological, individual, family, school, and community levels. Assessment and
      treatment guidelines are provided for Marriage and Family Therapists (MFTs), and
      specific areas of competency are proposed for MFTs who are working with children
      who have ADHD.

PMID- 16094813
TI  - Crisis management during "live" supervision: clinical and instructional matters.
AB  - In this article, we illustrate two examples of "live" supervision with marriage
      and family therapy trainees whose clients presented in the therapy room in
      immediate crisis. The case examples, one a client with suicidal thoughts and the
      other a parent who had struck her child, demonstrate how the university-based
      therapy team managed the recursive clinical and supervision processes that
      unfolded during the sessions. We present the case examples from the perspective
      of both supervisees and supervisor, discussing how our different experiences of
      the supervision unfolded in real time. Case discussion and reflections later in
      the article illustrate the need for an open, transparent, dialogical process
      throughout supervision. A case is made for supervisory participants to create
      alternative formats in which multiple supervisory voices can be heard.

PMID- 16094814
TI  - Family attachment narrative therapy: healing the experience of early childhood
      maltreatment.
AB  - Based on attachment theory and research, Family Attachment Narrative Therapy is
      introduced as a new family therapy modality developed to heal the experience of
      early childhood maltreatment. Unresolved childhood trauma has been correlated
      with impaired and delayed cognitive, behavioral and emotional functioning.
      Gentle, soothing, nonprovocative and nonintrusive narratives told by parents
      provide an alternative restorative experience designed to shift and change the
      child's destructive internal working model. The result is improved functioning
      and the ability to accept nurturing and care in relationships that offer love and
      safety. A representative case example is used to illustrate theory, practice and
      outcome. Pre- and posttherapy assessment supports the claim of improved
      functioning.

PMID- 16094815
TI  - Overcoming bias toward same-sex couples: a case study from inside an MFT ethics
      classroom.
AB  - This article illustrates a teaching case in which a marriage and family therapy
      (MFT) trainee learned to develop cultural sensitivity toward same-sex couples
      despite religious beliefs that put her at risk of discriminating against that
      population. The case took place during a marriage and family therapy ethics
      course in the spring of 2003. From two first-person perspectives, the authors
      illustrate the processes that facilitated the student's change, addressing the
      class activities, discussions, and pivotal moments of teaching and learning that
      promoted the student's cultural competency and helped her to resolve this
      personal and ethical dilemma. A set of classroom techniques (creating a safe
      environment, using a stance of curiosity, finding alternative learning formats,
      extrapolating ideas from multiple sources, and capitalizing on students'
      experiences outside of class) used in the case are detailed throughout the
      article.

PMID- 16094816
TI  - Resilience in Arab American couples after September 11, 2001: a systems
      perspective.
AB  - Guided by a family resiliency model grounded in systems theory and social
      constructionism, we conducted in-depth interviews to explore how 18 Arab American
      couples living in New York and New Jersey perceived and dealt with the terrorist
      attacks and aftereffects of September 11, 2001. Results are organized around five
      themes: Making sense of the attacks; the social environment after September 11,
      2001; construction of identity: Arab and/or American; how couples cope: reactions
      and resources; and immigration and acculturation. Clinical recommendations
      include helping couples to uncover and to explore conflicts in both Arab and
      American identities, using genograms to deal with family-of-origin histories,
      recognizing specific couple dynamics linked to traditional gender roles, helping
      couples connect to religious and cultural communities, and assessing
      acculturation.

PMID- 16094817
TI  - A twice-told tale: a phenomenological inquiry into clients' perceptions of
      therapy.
AB  - Typically, what we understand about therapy and the families we work with comes
      from the therapist's observations. This inquiry evolved out of the empirical data
      that indicate the dramatic importance of the client's perceptions to achieving a
      successful outcome. The research was guided by the understanding that it is
      vitally important for therapists and therapy researchers to listen to clients and
      to examine our practices and theoretical approaches in the light of the client's
      experience of them. This study is a phenomenological inquiry into the client's
      experience of therapy.

PMID- 16094818
TI  - Supervisees' perspectives of power use in supervision.
AB  - In this study, we examined the use of power in the supervisory relationship from
      supervisees' perspectives. Semistructured interviews of 11 supervisees in a
      Commission on Accreditation for Marriage and Family Therapy Education training
      program were conducted. From analysis of interview transcripts, themes about the
      ways in which supervisors and supervisees used power in the supervisory
      relationship emerged. Supervisors' power uses included discussions of power,
      empowering supervisees, promoting an atmosphere of safety, collaborating with
      supervisees, imposition of style/orientation, and misuses of power, such as
      violation of confidentiality. Themes for supervisees' power uses included
      supervisee-peer power, supervisees as consumers, and withholding information.
      Implications for researchers, supervisors, and supervisees are presented.

PMID- 16094819
TI  - Development of a one-step strip test for the diagnosis of chicken infectious
      bursal disease.
AB  - A rapid diagnostic strip for chicken infectious bursal disease (IBD) was
      developed based on membrane chromatography using high-affinity monoclonal
      antibodies directed to chicken infectious bursal disease virus (IBDV). The
      diagnostic strip has high specificity for detection of chicken IBDV antigen and
      recognizes a variety of the virus isolates, including virulent and attenuated
      strains, with no cross-reactivity to other viruses, such as Newcastle disease
      virus, Marek's disease virus, infectious bronchitis virus, infectious
      laryngotracheitis virus, and egg-drop-syndrome virus. The results showed that its
      specificity was highly consistent with the agar-gel precipitation test (AGP). The
      diagnostic strip detected as low as 800 median egg lethal dose (ELD50) viruses in
      the IBDV BC6/85-infected sample, which was comparable with AC-ELISA (400 ELD50)
      and 32 times more sensitive than the AGP test (2.56 x 10(4) ELD50). In
      experimental infection, IBDV was detected in the bursa as early as 36 hr
      postinfection with the diagnostic strip before the clinical signs and gross
      lesions appeared. It takes only 1-2 min to do a strip test to detect chicken IBDV
      antigen after the specimen is grounded in a whirl pack with finger massage.

PMID- 16094820
TI  - Development of antigen-capture enzyme-linked immunosorbent assay and RT-PCR for
      detection of turkey astroviruses.
AB  - Turkey astrovirus (TAstV) is an important agent of poult enteritis. The diagnosis
      of astroviruses has been dependent mainly on electron microscopy (EM) or immune
      EM (IEM). To develop other simple, rapid, and reliable diagnostic assays, two
      antigen-capture enzyme-linked immunosorbent assays (AC-ELISAs), polyclonal AC
      ELISA and monoclonal AC-ELISA, were developed in this study. Monoplex and
      multiplex reverse transcription-polymerase chain reactions (RT-PCRs) were also
      developed using nondegenerate primer sets specific to the capsid region and
      degenerate primer pairs specific to the polymerase area of two TAstV. EM was
      included for comparison. Fecal or intestinal contents samples from naturally and
      experimentally infected poults with enteritis were examined using the developed
      assays. The polyclonal AC-ELISA had higher sensitivity and wider detection
      spectrum than the monoclonal AC-ELISA with group-specific monoclonal antibody
      (MAb), whereas the monoclonal AC-ELISA had very high specificity but lower
      sensitivity, which was estimated at 0.06 microg of viral proteins. Small round
      viruses (SRV) that could be astroviruses or other small viruses were detected in
      34.4% of the samples examined by EM. The monoplex RT-PCR results amplified with
      primers SRV-1-3 and SRV-1-5 revealed that the positive rate of astroviruses was
      45.3%, which was 10.9% higher than that of EM even if other SRVs were not
      excluded. Multiplex RT-PCR with SRV-1-3 and SRV-1-5 and AFCP-F1 and AFCP-R1 and
      the monoplex RT-PCR with degenerate primers verified that the positive rate of
      astroviruses was 59.4%, which was 25% higher than that of EM. Both RT-PCRs showed
      good specificity and wider detection spectrum compared with earlier published
      data.

PMID- 16094821
TI  - Longitudinal monitoring of two commercial layer flocks and their environments for
      Salmonella enterica serovar enteritidis and other Salmonellae.
AB  - Between August 20, 2001, and September 17, 2002, 1429 samples including drag
      swabs, egg belt or egg rollout swabs, fan-blade swabs, rodent organ and
      intestinal pools, beetle (Alphitobius diaperinus) pools, housefly (Musca
      domestica) pools, chicken organ and intestinal pools, and egg pools were obtained
      for Salmonella culture from two flocks from two different commercial layer
      ranches. The two ranches were purposefully selected for the study based on their
      previous status of Salmonella Enteritidis isolation using environmental drag
      swabs in cooperation with practicing veterinarians. Salmonella sp. was isolated
      from 337 out of 979 (34.42%) non-egg samples. No Salmonella was isolated from 450
      egg pools collected from either ranch. S. enteritidis was isolated from samples
      obtained from ranch 1 from manure drag swabs, 4/284 (1.4%); rodent organs, 1/24
      (4.2%); and housefly pool cultures 1/21 (4.8%). Salmonella Enteritidis was
      isolated from ranch 2 from mouse organ and intestinal pool samples, 1/24 (4.2%).
      Salmonella group B was isolated from all sample types except the insects. There
      was a statistically significant difference in isolation rates among seven
      serogroups of Salmonella: groups B, C1, C2, D, E, K, and untypeable (Pearson chi
      square 18.96, P = 0.002). Overall, statistically significant differences were
      observed with respect to Salmonella isolation among the types of samples taken
      (Pearson chi-square 118.54, P < 0.0001). Intensive monitoring for Salmonella
      Enteritidis can be used to optimize a Salmonella reduction program for an
      individual poultry biosecurity unit.

PMID- 16094822
TI  - The isolation of exotic Newcastle disease (END) virus from nonpoultry avian
      species associated with the epidemic of END in chickens in southern California:
      2002-2003.
AB  - During the first 11 months of the 2002-2003 exotic Newcastle disease (END)
      epidemic in chickens in southern California, a total of 27,688 cloacal and
      tracheal (oropharyngeal) swab pools and/or tissue pools from 86 different avian
      species other than chickens and turkeys were submitted for Newcastle disease
      virus (NDV) isolation and characterization. Fifty-seven specimens (0.23%),
      representing 12 species of birds and 13 unspecified species, from a total of
      24,409 accessions or submissions were positive for NDV. The NDV isolate was
      characterized as ENDV by real-time reverse transcription-polymerase chain
      reaction (RT-PCR). Of the 11,486 premises with other avian species, 1599 also had
      chickens. There were 1900 positive chicken samples from 164 premises, and 56
      positive other avian species from 51 premises. Twelve premises had both positive
      chickens and positive other avian species. All positive other avian species were
      located on premises either on or within a 1 km radius of known infected premises.
      In this epidemic, premises with positive other avian species were significantly
      more likely to have chickens, and were significantly more likely to have positive
      chickens (OR = 3.7, P < 0.0001).

PMID- 16094823
TI  - A Marek's disease virus vIL-8 deletion mutant has attenuated virulence and
      confers protection against challenge with a very virulent plus strain.
AB  - Marek's disease virus (MDV) is an alpha-herpesvirus that causes rapid development
      of T-cell lymphomas in chickens. MDV-encoded vIL-8 is homologous to the cellular
      IL-8 gene, and its function in MDV pathogenesis has yet to be determined. Using
      overlapping cosmid clone-based technology, we have generated an MDV vIL-8
      deletion mutant virus, rMd5/delta vIL-8. In vivo experiments with this mutant
      virus demonstrated that deletion of vIL-8 results in attenuation of the virus and
      induction of significantly less gross tumor, both in viscera and nerves, when
      compared to the parental virus. Reintroduction of the vIL-8 gene in the genome of
      the mutant virus restored the virulence of the virus to the wild-type levels,
      indicating that vIL-8 plays a role in MDV-induced pathogenesis. In this study, we
      show that there is a significant difference in the reduction of B cells and
      activation of T cells in the spleen cells of chickens inoculated with parental
      rMd5 and vIL-8 deletion mutant virus. These results indicate that vIL-8 is
      involved in the early phase of pathogenesis, presumably by attracting target
      cells to the initial site of infection. In addition, protection studies with the
      vIL-8 mutant virus showed that this mildly virulent virus protects susceptible
      maternal antibody-positive viruses at a higher level than the commonly used
      serotype 1 CVI988 vaccine. These results confirm the potential of partially
      attenuated viruses as vaccines against very virulent plus strains and the
      usefulness of recombinant DNA technology to generate the next generation of MDV
      vaccines.

PMID- 16094824
TI  - Isolation and characterization of H3N2 influenza A virus from turkeys.
AB  - Five 34-wk-old turkey breeder layer flocks in separate houses of 2550 birds each
      in a single farm in Ohio experienced a drop in egg production from late January
      to early February 2004. Tracheal swabs (n = 60), cloacal swabs (n = 50), and
      convalescent sera (n = 110) from the flocks were submitted to the laboratory for
      diagnostics. Virus isolation was attempted in specific-pathogen free embryonating
      chicken eggs and Vero and MDCK cells. Virus characterization was performed using
      agar gel immunodiffusion, the hemagglutination test, the hemagglutination
      inhibition test, the virus neutralization test, reverse transcription-polymerase
      chain reaction, sequencing, and phylogenetic analysis. A presumptive influenza
      virus was successfully propagated and isolated on the first passage in MDCK
      cells, but initially not in Vero cells or specific-pathogen free chicken embryos.
      After two passages in MDCK cells, it was possible to propagate the isolate in
      specific-pathogen free chicken embryos. Preliminary sequence analysis of the
      isolated virus confirmed that it was influenza A virus with almost 100% (235/236)
      identity with the matrix gene of a swine influenza A virus,
      A/Swine/Illinois/100084/01 (H1N2). However, it was not possible to subtype the
      virus using conventional serotyping methods. The results of genetic
      characterization of the isolated virus showed that it was the H3N2 subtype and
      was designated as A/Turkey/OH/313053/04 (H3N2). Phylogenetic analysis of the
      eight gene segments of the virus showed that A/Turkey/OH/313053/04 (H3N2) isolate
      was most closely related to the triple-reassortant H3N2 swine viruses
      [A/Swine/WI/14094/99 (H3N2)] that have been circulating among pigs in the United
      States since 1998, which contains gene segments from avian, swine, and human
      viruses. The A/Turkey/OH/313053/04 (H3N2) isolated from turkeys in this study was
      classified as a low pathogenic avian influenza A virus because it only caused a
      drop in egg production with minor other clinical signs and no mortality.

PMID- 16094825
TI  - Response of white leghorn chickens of various B haplotypes to infection at hatch
      with subgroup J avian leukosis virus.
AB  - White leghorn chickens from seven 15.B congenic lines (genetically similar except
      for genes linked to the major histocompatibility complex [MHC] B haplotype) and
      two Line 0.B semicongenic lines were infected at hatch with strain ADOL Hc-1 of
      subgroup J avian leukosis virus (ALV-J). At 5, 8, 16, and 36 wk of age, chickens
      were tested for viremia, serum-neutralizing antibody, and cloacal shedding.
      Chickens were also monitored for development of neoplasia. In the 15.B congenic
      lines (B*2, B*5, B*12, B*13, B*15, B*19, and B*21) there were no significant
      differences in the incidence of viremia between B haplotypes. In fact, infection
      at hatch in all of the 15.B congenic lines induced tolerance to ALV-J because
      100% of these chickens were viremic and transient circulating serum-neutralizing
      antibody was detected in only a few chickens throughout the 36 wk experiment.
      However, at 16 wk of age more B*15 chickens had antibody and fewer B*15 chickens
      shed virus than did the 16-wk-old B*2, B*5, or B*13 chickens. Moreover, compared
      with B*15 chickens, a higher percentage of B*13 chickens consistently shed virus
      from 8 wk postinfection to termination at 36 wk postinfection. The B haplotype
      had a transient effect on viral clearance in Line 0.B semicongenics, as more B*13
      than B*21 chickens remained viremic through 5 wk of age. Very few (0%-18%) of the
      Line 0.B semicongenic chickens shed virus. By 36 wk of age, all Line 0 B*13 and
      B*21 chickens produced serum-neutralizing antibodies and cleared the virus. These
      results show that following ALV-J infection at hatch the immune response is
      influenced transiently by the B haplotype and strongly by the line of chicken.
      Although this study was not designed to study the effect of endogenous virus on
      ALV-J infection, the data suggest that endogenous virus expression reduced
      immunity to ALV-J in Line 15I5, compared with Line 0, a line known to lack
      endogenous virus genes.

PMID- 16094826
TI  - Molecular epidemiology of infectious bursal disease viruses: distribution and
      genetic analysis of newly emerging viruses in the United States.
AB  - Genetic mutations in the genome of infectious bursal disease virus (IBDV) have
      resulted in antigenic and pathogenic variants that continue to cause disease in
      commercially reared chickens. The extent of the genetic diversity among IBDV
      strains circulating in the United States is unknown. This study was designed to
      identify newly emerging viruses infecting chickens on poultry farms experiencing
      immune suppression-related problems. Fifty IBDV-positive samples were identified
      from 273 bursa samples using a real-time reverse transcription-polymerase chain
      reaction (RT-PCR) assay. Mutation probes were designed to the hydrophilic B
      coding region of the VP2 gene. Six mutation probes used in this study were based
      on the nucleotide sequences of the Del-E, Bursine 2, D-78, STC, G6, and T1 IBDV
      strains. Following real-time RT-PCR, these mutation probes identified 11 of the
      50 viruses in the melting temperature (Tm) analysis. The results indicated that
      the remaining 39 viruses had one or more nucleotide mutations compared with the
      six mutation probes in this region of the VP2 gene. Thirty-eight viruses were
      chosen for nucleotide sequence analysis across the hypervariable region of the
      VP2 gene. Within this group of 38 viruses, four were identified by the mutation
      probes and their nucleotide sequences confirmed that real-time RT-PCR data. In
      the remaining 34 viruses, nucleotide mutations were observed in as many as 8 of
      23 nucleotides across the hydrophilic B epitope coding region. Furthermore, every
      amino acid position except one between 316 and 324 had at least one substitution
      mutation. Phylogenic analysis placed two of the 38 viruses sequenced on branches
      with classic viruses and the remaining 36 viruses were placed on four distinct
      branches. Branches 1 and 2 contained a majority of the viruses, which were
      distributed across most of the major poultry-producing states in the United
      States. These branches contained previously characterized variant IBDV strains.
      Viruses in branches 3 and 4 were confined to three states and did not contain any
      previously characterized IBDV strains.

PMID- 16094827
TI  - Reverse transcriptase-polymerase chain reaction to detect avian encephalomyelitis
      virus.
AB  - A reverse transcriptase-polymerase chain reaction (RT-PCR) was developed and
      optimized for the detection of avian encephalomyelitis virus (AEV). A pair of
      primers was prepared based on the VP2 gene of the structural protein P1 region of
      the AEV genome. An avian encephalomyelitis virus-specific 619-base pair cDNA
      product was amplified by these primers from five reference/field strains of AEVs
      but not from 10 other avian pathogenic viruses and bacteria. The RT-PCR assay
      developed in this study was found to be sensitive and specific with as little as
      10 pg of avian encephalomyelitis virus RNA detected using gel electrophoresis.
      Furthermore, AEV-RT-PCR was able to detect AE virus from chicken embryo brain at
      3 days postinoculation as compared with the AE agar gel precipitation test (AGP),
      which required up to 11 days of incubation in the embryos.

PMID- 16094828
TI  - Protective efficacy of intermediate and intermediate plus infectious bursal
      disease virus (IBDV) vaccines against very virulent IBDV in commercial broilers.
AB  - The evolution of very virulent (vv) infectious bursal disease virus (IBDV) has
      led to significant economic losses in many poultry-producing areas. Despite
      vigorous vaccination strategies, IBDV has been difficult to control. The
      protective efficacy of IBDV vaccines is traditionally evaluated in specific
      pathogen-free (SPF) chickens. But under field conditions, residual maternal
      antibody (mAb) levels may interfere with vaccine efficacy. In this study,
      commercial broilers with various levels of maternally derived antibodies were
      vaccinated with IBDV vaccines of different virulence (vaccines 1-3, intermediate;
      vaccine 4, intermediate plus). At an average maternal virus-neutralizing antibody
      (mAb) level of log2 10.8 (range 7.6-11.6) at day of vaccination, only the
      intermediate plus vaccine induced IBDV antibodies after 18 days, while the other
      intermediate vaccines did not. At average mAb levels of log2 6.7 (range 5.6-8.6)
      at day of vaccination, all vaccines induced circulating antibodies, although the
      onset of antibody production differed significantly between strains (P < 0.05).
      While the intermediate plus vaccine induced enzyme-linked immunosorbent assay
      antibody levels already at 14 days postvaccination (PV), the intermediate
      vaccines induced significant antibody levels 28 (vaccines 1, 2) and 35 (vaccine
      3) days PV. The time of IBDV antibody induction correlated with the onset of
      bursa lesions. The severity of lesions was comparable between vaccines 1, 3, and
      4 (lesion score 4), while vaccine 2 induce only mild lesions of score 1 in 23% of
      the tested birds. Despite the induction of antibodies, none of the tested
      vaccines fully protected against challenge with vvIBDV. All challenged birds had
      either significantly higher bursal lesion scores or a higher IBDV antigen load in
      the bursa or sometimes both in comparison with nonchallenged birds (P < 0.05).
      Our study demonstrates that the evaluation of IBDV-vaccine efficacy is difficult
      in commercial broilers. For the first time, it was shown that the onset of bursa
      lesions and recovery of IBDV-vaccinated broilers is delayed in the presence of
      mAb in comparison with SPF chickens but not suppressed as previously assumed. At
      the time of challenge, vaccinated birds may still have significant bursa lesions
      and may lack target cells for IBDV-challenge virus. To be able to evaluate
      vaccine efficacy in commercial broilers, parameters such as intrabursal IBDV
      antigen load should also be considered in conjunction with bursa lesion scores.

PMID- 16094829
TI  - Use of mgc2-polymerase chain reaction-restriction fragment length polymorphism
      for rapid differentiation between field isolates and vaccine strains of
      Mycoplasma gallisepticum in Israel.
AB  - Increasing use of Mycoplasma gallisepticum (MG) live vaccines has led to a need
      for a rapid test for differentiation of MG field strains from the live vaccine
      strains ts-11 and 6/85. We examined the differentiating potential of diagnostic
      polymerase chain reaction (PCR) primers targeted to the gene mgc2, encoding a
      cytadherence-related surface protein uniquely present in MG. The mgc2-PCR
      diagnostic primers are specific for MG in tests of all avian mycoplasmas or
      bacteria present in the chicken trachea and are sensitive enough to readily
      detect MG in tracheal swabs from field outbreaks. Differentiation of vaccine
      strain ts-11 was based on identification of restriction enzyme sites in the 300
      base-pair (bp) mgc2-PCR amplicon present in ts-11 and missing in MG isolates from
      field outbreaks in Israel. Restriction sites for the enzymes HaeII and SfaN1 were
      identified in the amplified region in strain ts-11 and were not found in 28 field
      isolates of MG, comprising a representative cross section of all the MG isolates
      from the period 1997-2003. In practice, differential diagnosis of MG is achieved
      within 1 day of submission of tracheal swab samples by mgc2-PCR amplification and
      restriction of the amplicon with HaeII, giving a 270-bp fragment for ts-11 or no
      restriction for other MG strains tested. Application of the mgc2-PCR-restriction
      fragment length polymorphism (mgc2-PCR-RFLP) assay enabled differential diagnosis
      of both components of a mixture of ts-11 and non-ts-11 DNA, detecting the field
      strain in the presence of a large excess of ts-11. The test was successfully
      applied in vivo for monitoring vaccinates in a ts-11 vaccine trial. In principle,
      the test may also be used to identify the 6/85 vaccine strain, which yields a 237
      bp product, readily differentiated from the approximately 300-bp PCR product of
      all other strains tested. Further testing of field isolates will be necessary to
      determine the applicability of this test in the United States and other
      countries.

PMID- 16094830
TI  - Molecular studies on suspect very virulent infectious bursal disease virus
      genomic RNA samples.
AB  - Infectious bursal disease (IBD) associated with high mortality was first observed
      in Europe in the mid-1980s. The viruses identified in those outbreaks were
      described as being very virulent infectious bursal disease virus (vvIBDV)
      strains. These viruses have spread to nearly every continent but have not yet
      been identified in North America, Australia, and New Zealand. There is a real and
      immediate concern that the very virulent form of IBDV will continue to spread
      until it is present on every continent. Genomic RNA samples from IBDV strains
      suspected of being very virulent were submitted to our laboratory for molecular
      analysis. Nucleotide sequences of the VP2 gene hypervariable sequence region were
      determined for 18 of these viruses. A comparison with published vvIBDV sequences
      indicated that all but one sample (Thai 4) had nucleotide and predicted amino
      acid sequences consistent with vvIBDV strains. Published sequences and the
      nucleotide sequences of our 17 putative vvIBDV strains were used to identify
      unique nucleotides in the VP2 gene. Probe pairs for a real-time reverse
      transcriptase-polymerase chain reaction (RT-PCR) assay were designed based on
      these unique sequences and then used to test the 17 genomic samples that were
      identified by nucleotide sequencing to be consistent with vvIBDV, plus the one
      Thai 4 sample that was not consistent with vvIBDV. Using melting temperature (Tm)
      analysis following real-time RT-PCR, two probe pairs (vv232 and vv256)
      successfully identified the 17 putative vvIBDV strains and distinguished them
      from the Thai 4 sample. An additional 26 genomic RNA samples submitted as suspect
      vvIBDV strains were then tested using the vv232 and vv256 probes. Based on the
      melting point analysis of these two probes, all 26 samples contained nucleotide
      sequences consistent with vvIBDV strains. The specificity of the vv232 and vv256
      probe pairs was evaluated using 19 non-vvIBDV strains. In every case, the probes
      distinguished the 19 classic and variant (non-vvIBDV) strains from the putative
      vvIBDV strains. Diagnostic assays that can reliably identify vvIBDV strains are
      needed for surveillance programs designed to monitor the spread of these viruses.

PMID- 16094831
TI  - Pathologic and immunohistochemical findings in goshawks (Accipiter gentilis) and
      great horned owls (Bubo virginianus) naturally infected with West Nile virus.
AB  - The carcasses of 25 great horned owls and 12 goshawks were investigated for West
      Nile virus (WNV) infection by immunohistochemistry (IHC) performed on various
      organs, including brain, spinal cord, heart, kidney, eye, bone marrow, spleen,
      liver, lungs, pancreas, intestine, and proventriculus, using a WNV-antigen
      specific monoclonal antibody and by WNV-specific reverse transcriptase-polymerase
      chain reaction (RT-PCR), performed on fresh brain tissue only. WNV infection was
      diagnosed by IHC in all owls and all goshawks. WNV-specific RT-PCR amplified WNV
      RNA in the brain of all goshawks but only 12 owls (48%). Cachexia was a common
      macroscopic finding associated with WNV infection in owls (76%). Myocarditis was
      occasionally macroscopically evident in goshawks (33%). Microscopically,
      inflammatory lesions, including lymphoplasmacytic and histiocytic encephalitis,
      myocarditis, endophthalmitis, and pancreatitis were present in both species but
      were more common and more severe in goshawks than in owls. The most
      characteristic brain lesion in owls was the formation of glial nodules, in
      particular in the molecular layer of the cerebellum, while encephalitis affecting
      the periventricular parenchyma of the cerebral cortex was common in the goshawks.
      In owls, WNV-antigen-positive cells were present usually only in very small
      numbers per organ. Kidney (80%), heart (39%), and cerebellum (37%) were the
      organs that most commonly contained WNV antigen in owls. WNV antigen was
      frequently widely distributed in the organs of infected goshawks, with increased
      amounts of WNV antigen in the heart and the cerebrum. Spleen (75%), cerebellum
      (66%), heart (58%), cerebrum (58%), and eye (50%) were often WNV-antigen positive
      in goshawks. In contrast with the goshawks, WNV antigen was not present in
      cerebral and retinal neurons of owls. WNV infection appears to be capable of
      causing fatal disease in great horned owls and goshawks. However, the
      distribution and severity of histologic lesions, the antigen distribution in the
      various organs, and the amount of antigen varied among both species. Therefore,
      the diagnostician may choose organs for histology and immunohistochemistry as
      well as RT-PCR depending on the investigated species in order to avoid false
      negative results.

PMID- 16094832
TI  - Comparison of culture, PCR, and different serologic tests for detection of
      Mycoplasma gallisepticum and Mycoplasma synoviae infections.
AB  - In this study, the technical performance of culture, two commercially available
      polymerase chain reaction (PCR) tests, rapid plate agglutination (RPA) test,
      hemagglutination inhibition (HI) test, and eight commercially available enzyme
      linked immunosorbent assays (ELISAs) were compared for the detection of avian
      mycoplasma infections from 3 days postinfection (d.p.i.) through 35 d.p.i. The
      tests were carried out on samples from specified pathogen-free layers that were
      infected at 66 wk of age with recent Mycoplasma synoviae (MS) and Mycoplasma
      gallisepticum (MG) field strains, MS and MG ATCC strains, and Mycoplasma imitans
      (MIM), respectively. Results showed a high percentage of positive samples in the
      homologous infected groups and a high percentage of negative samples (100%) in
      the uninfected and heterologous infected groups during 35 d.p.i. of both culture
      and PCR tests. For the group infected with the MG 15302 ATCC strain, serology was
      more sensitive than bacteriology. All MG and MS tests, with the exception of MG
      ELISA kit D showed a lower percentage of positive samples during 35 d.p.i. for
      the detection of the MG and MS ATCC strain infection compared with that of the
      field strains. Also, the number of cross-reactions (false positives) in the
      serologic tests was lower after infection with an ATCC strain than after an
      infection with the MG or MS field strain. Contradictory to other studies, the
      ELISAs and the RPA test using undiluted serum showed a relatively high number of
      false-positive results. The MG ELISAs (except ELISA kit D) showed more false
      positive results (up to 37%) in the MIM-infected group than in the MS-infected
      groups. This was not unexpected, as MIM and MG have a close antigenic
      relationship. The results of the serologic tests in this study showed that a
      certain level of false-positive results can be expected in about any serologic
      test. Although the level of false-positive results varied between several
      serologic tests, this study showed that it is not advisable to rely completely on
      one test (system) only.

PMID- 16094833
TI  - Rapid detection of virulence-associated genes in avian pathogenic Escherichia
      coli by multiplex polymerase chain reaction.
AB  - Based on recently published prevalence data of virulence-associated factors in
      avian pathogenic Escherichia coli (APEC) and their roles in the pathogenesis of
      colibacillosis, we developed a multiplex polymerase chain reaction (PCR) as a
      molecular tool supplementing current diagnostic schemes that mainly rely on
      serological examination of strains isolated from diseased birds. Multiple
      isolates of E. coli from clinical cases of colibacillosis known to possess
      different combinations of eight genes were used as sources of template DNA to
      develop the multiplex PCR protocol, targeting genes for P-fimbriae (papC),
      aerobactin (iucD), iron-repressible protein (irp2), temperature-sensitive
      hemagglutinin (tsh), vacuolating autotransporter toxin (vat), enteroaggregative
      toxin (astA), increased serum survival protein (iss), and colicin V plasmid
      operon genes (cva/cvi). In order to verify the usefulness of this diagnostic
      tool, E. coli strains isolated from fecal samples of clinically healthy chickens
      were also included in this study, as were uropathogenic (UPEC), necrotoxigenic,
      and diarrhegenic E. coli strains. The application of the multiplex PCR protocol
      to 14 E. coli strains isolated from septicemic poultry showed that these strains
      harbored four to eight of the genes mentioned above. In contrast, those isolates
      that have been shown to be nonpathogenic for 5-wk-old chickens possessed either
      none or, at most, three of these genes. We found only one enterohemorrhagic
      (EHEC), one enteropathogenic (EPEC), and two enterotoxic (ETEC) E. coli strains
      positive for irp2, and another two ETEC strains positive for astA. As expected,
      UPEC isolates yielded different combinations of the genes iss, papC, iucD, irp2,
      and a sequence similar to vat. However, neither the colicin V operon genes
      cva/cvi nor tsh were amplified in UPEC isolates. The multiplex PCR results were
      compared with those obtained by DNA-DNA-hybridization analyses to validate the
      specificity of oligonucleotide primers, and the protocol was concluded to be a
      useful, sensitive, and rapid assay system to detect avian pathogenic E. coli and
      differentiate them from nonpathogenic strains and those belonging to other
      pathotypes.

PMID- 16094834
TI  - Effects of Fusarium moniliforme culture material containing known levels of
      fumonisin B1 on progress of Salmonella Gallinarum infection in Japanese quail:
      clinical signs and hematologic studies.
AB  - To study the individual and combined effects of fumonisin B1 (FB1) toxicity and
      Salmonella serotype Gallinarum infection, Japanese quail (Coturnix coturnix
      japonica) were fed Fusarium moniliforme culture material (2.5%), 150 mg FB1/kg
      ration, and were subsequently challenged orally with Salmonella Gallinarum
      organisms (2 x 10(4) colony-forming units) at 21 days of age. The chicks were fed
      culture material containing FB1 from day 5 till the end of the experiment. After
      being infected with Salmonella Gallinarum, observations were made 1, 2, 3, 5, 7,
      10, 14, and 21 days postinfection. The clinical signs of diarrhea with bloody
      discharges were more pronounced in the Salmonella-infected birds on the FB1 diet.
      Mortality caused by Salmonella Gallinarum increased by 12% in the presence of
      FB1. Mean body weights in both the Salmonella-infected and FB1-fed groups were
      significantly lower than those of the controls at almost all intervals. Mean
      values of hemoglobin, packed cell volume, and total erythrocyte count were
      slightly higher in birds fed FB1 but were lower in the Salmonella Gallinarum
      groups fed FB1 and plain chick mash. Anemia was evident, between 5 and 10 days
      postinfection, in quail chicks infected with Salmonella Gallinarum alone. Total
      leukocyte counts were higher in Salmonella-infected and FB1-fed groups because of
      an increase in the number of heterophils and lymphocytes. However, the increase
      in lymphocyte response to infection was lower by 4.27%-30.09% between 3 and 21
      days postinfection in the FB1-fed chicks compared with chicks infected with
      Salmonella Gallinarum. Alanine transaminase and total serum protein were slightly
      higher in both the infected and FB1-fed groups. This study revealed that the
      continuous presence of fumonisins in the diets of quail chicks might increase the
      susceptibility to or the severity of Salmonella Gallinarum infection.

PMID- 16094835
TI  - Yeast-derived sigma C protein-induced immunity against avian reovirus.
AB  - Avian reoviruses (ARVs) can result in disease and economic losses in the poultry
      industry. Vaccines against ARV may not provide full protection and can cause
      adverse reactions. The coding sequence of the sigma C protein from strain S1133
      of avian reovirus was expressed in Schizasaccharomyces pombe. Sigma C protein
      expression was demonstrated by Western blotting, and the protein was evaluated
      for its ability to protect specific-pathogen-free (SPF) chickens against
      challenge with the virulent S1133 strain. Serologic and challenge-infection data
      showed the efficacy of the recombinant vaccine administered orally each week for
      3 consecutive wk. Sigma C protein induced antibody, as determined by enzyme
      linked immunosorbent assay. Percentage (%) protection induced by the low dose
      (125 microg purified yeast-expressed sigma C protein/chicken) or the high dose
      (250 microg purified yeast-expressed sigma C protein/chicken) was 64 and 91,
      respectively. The commercial vaccine administered once or twice provided 82%
      protection. Results supported the feasibility of a plant-derived vaccine for use
      in poultry immunization schemes.

PMID- 16094836
TI  - Presence of naturally occurring Campylobacter and Salmonella in the mature and
      immature ovarian follicles of late-life broiler breeder hens.
AB  - Campylobacter and Salmonella are known to cause acute bacterial gastroenteritis
      in humans. Raw poultry products have been implicated as a significant source of
      these infections. Five trials were conducted to determine whether Campylobacter
      and Salmonella spp. exist naturally in the mature and immature ovarian follicles
      of late-life broiler breeder hens. Broiler breeder hens ranging from 60 to 66 wk
      of age were obtained from four different commercial breeder operations. For each
      trial, the hens were removed from the commercial operation and held overnight at
      the University of Georgia processing facility. The hens were euthanized,
      defeathered, and aseptically opened. To reduce the possibility of cross
      contamination between samples, first the mature and immature ovarian follicles,
      then the ceca, were aseptically removed. Individual samples were placed in
      sterile bags, packed on ice, and transported to the laboratory for evaluation.
      Overall, Campylobacter was found in 7 of 55 immature follicles, 12 of 47 mature
      follicles, and 41 of 55 ceca. Campylobacter was found in at least one of each
      sample of mature follicles and in ceca in each of the five trials. Salmonella was
      found in 0 of 55 immature follicles, 1 of 47 mature follicles, and 8 of 55 ceca.
      In this study, the recovery rate of Salmonella from late-life broiler breeder hen
      ovarian follicles was relatively low. However, the recovery rate of Campylobacter
      from the hen ovarian follicles was reasonably high, suggesting that these breeder
      hens could be infecting fertile hatching eggs. Determining how Campylobacter
      contaminated these ovarian follicles and how many chicks could be colonized from
      this source are the next steps in helping to elucidate a better understanding of
      this ecology and the control of Campylobacter in poultry production.

PMID- 16094837
TI  - Diagnosis of zinc phosphide poisoning in chickens using a new analytical
      approach.
AB  - Approximately 200 chickens were found dead after the flooring of a slat-and
      litter house was breached. No clinical signs of illness were observed in the
      surviving birds. During necropsy, rolled oats were found in the chickens' crops
      and gizzards, and the contents had a petroleum-like odor. Histopathologic
      examination revealed severe pulmonary edema and congestion of the chickens'
      lungs, hearts, livers, and kidneys. Based on the history and necropsy findings,
      zinc phosphide exposure was suspected. Diagnosis of zinc phosphide poisoning has
      previously been based on history of exposure, identification of the bait material
      in the gastrointestinal tract, and chemical detection of phosphine gas. However,
      currently available diagnostic methods are nonconfirmatory, and may produce false
      positive results. The objective of this case report was to determine whether the
      sudden death described in these chickens was caused by the ingestion of zinc
      phosphide, by developing a sensitive and highly specific gas chromatography/mass
      spectrometry (GC/MS) methodology for analysis of the gastrointestinal samples
      submitted to the laboratory. It was also found that the determination of zinc
      concentrations in liver or kidney tissue or stomach contents is not a reliable
      indicator of zinc phosphide poisoning.

PMID- 16094838
TI  - Wintering of neurotropic velogenic Newcastle disease virus and West Nile virus in
      double-crested cormorants (Phalacrocorax auritus) from the Florida Keys.
AB  - During November 2002, six double-crested cormorants (DCCs; Phalacrocorax auritus)
      were found moribund in Big Pine Key, FL, exhibiting clinical signs indicative of
      neurologic disease. Postmortem diagnostic evaluations were performed on two adult
      birds. Virulent Newcastle disease virus (NDV) was isolated from a cloacal swab
      from cormorant 1. West Nile virus (WNV) was isolated from the brain and lung of
      cormorant 2. Nucleotide sequence analysis of a portion of the fusion (F) protein
      gene of the NDV cormorant isolate revealed it shared a 100% deduced amino acid
      identity with only two viruses: the 1992 epizootic cormorant isolate from
      Minnesota and the 1992 turkey isolate from North Dakota. The epidemiologic
      significance of the recognition of virulent NDV on cormorant wintering grounds
      during a nonepizootic period, in addition to the potential implications of the
      concurrent isolation of NDV and WNV from cormorants, is discussed.

PMID- 16094839
TI  - First report of parasitic esophagitis by Streptocara incognita in Muscovy ducks
      (Cairina moschata domesticus) in Italy.
AB  - This work describes the first outbreak of streptocariasis by Streptocara
      incognita reported from Italy. The disease was observed in a backyard flock of 62
      ducks (Cairina moschata domesticus) located in Treviso, northeastern Italy.
      Fifteen birds died in a period of 2 wk, showing debilitation and emaciation. Two
      ducks were submitted for postmortem examination and an esophagitis associated
      with nematodes was observed. The nematodes were identified as Streptocara
      incognita.

PMID- 16094840
TI  - Toxicoinfectious botulism in commercial caponized chickens.
AB  - During the summer of 2003, two flocks of commercial broiler chickens experienced
      unusually high death losses following caponizing at 3 wk of age and again between
      8 and 14 wk of age. In September, fifteen 11-wk-old live capons were submitted to
      the Iowa State University Veterinary Diagnostic Laboratory for assistance. In
      both flocks, the second episode of elevated mortality was associated with
      incoordination, flaccid paralysis of leg, wing, and neck muscles, a recumbent
      body posture characterized by neck extension, and diarrhea. No macroscopic or
      microscopic lesions were detected in affected chickens. Hearts containing dotted
      blood and ceca were submitted to the National Wildlife Health Center in Madison,
      WI. Type C. botulinum toxin was identified in heart blood and ceca by mouse
      bioassay tests. Enzyme-linked immunosorbent assay tests on heart blood samples
      were also positive for type C. botulinum toxin. Clostridium botulinum was
      isolated from the ceca and genes encoding type C. botulinum toxin were detected
      in cecal contents by a polymerase chain reaction test. Chickens are less
      susceptible to botulism as they age, and this disease has not previously been
      documented in broilers as old as 14 wk of age. Wound contamination by spores of
      C. botulinum may have contributed to the unusually high death losses following
      caponizing.

PMID- 16094841
TI  - Omphalitis associated with Aspergillus fumigatus in poults.
AB  - Omphalitis associated with aspergillosis was diagnosed in four cases of
      commercial turkey poults ranging in age from 3 to 9 days old. In two cases, the
      mycotic agent present in the yolk sac was isolated and identified as Aspergillus
      fumigatus. In the other two cases, the fungi were identified as Aspergillus sp.
      on the basis of morphologic characteristics of the fungi in tissue sections. The
      fungi present were further confirmed to be of the genus Aspergillus by
      immunohistochemistry. Omphalitis by A. fumigatus infection has not been
      documented before.

PMID- 16094842
TI  - Diagnosis and successful treatment of a presumptive case of aspergillosis in a
      Micronesian kingfisher (Halcyon cinnamomina cinnamomina).
AB  - A 4-yr-old male Micronesian kingfisher was suspected of having an aspergillus
      infection. The infection was thought to be related to stress associated with
      movement to a new enclosure/exhibit and cage-mate aggression. The diagnosis was
      based on an elevated white cell count, positive antibody and antigen aspergillus
      titers, and abnormal plasma protein electrophoresis characterized by a moderate
      elevation of alpha2 and severe elevation on the beta protein fractions. The bird
      was treated with antifungal medication administered systemically and by
      nebulization for 10 wk. Response to treatment was monitored by serial white cell
      counts and plasma electrophoresis. Clinical improvement in this bird was
      correlated with a return of the white blood cell count to normal levels and what
      was considered a normal protein electrophoresis distribution.

PMID- 16094843
TI  - [Epidemiological transition and health impact of cardiovascular disease in
      Tunisia].
AB  - OBJECTIVE: We aim at analysing the increase of CVDs in the Tunisian hospitals in
      order to assess the burden of NCDs in the transitional context. METHODS: Data are
      recorded through the Tunisian National Morbidity and Mortality Survey (TNMMS). In
      order to assess the CVDs (CHDs vs RHDs) trend, two representative samples of
      Cardiology Departements patients were compared one is selected from the TNMMS and
      the second from the hospitalisations recorded in 1992. Causes, stay duration,
      status at the end of the hospitalisation, transfer to another hospital and
      patients socio-demographic characteristics are recorded and compared for the two
      periods. All the diagnosis are coded referring to the DMC 10. To analyze the
      determinant of the epidemiological transition, we have elaborated the CVD causal
      pattern and we have documented all their determinants. RESULTS: CHD rate has
      dramatically increased, while RHD has decreased especially on men. In 1992, 39.2%
      of men and 11.8% of women were admitted for CHD. In 2002, these rate are
      respectivly 58.8% and 38.2% while RHD rates were, in 1992, 11.8% on men and 25.3%
      on women vs 4.4% and 11.7% respectively. CONCLUSION: This study has confirmed
      that so far controlling transmitted diseases seems to be successful, Tunisian
      people are about to face a new problems as hypertension, obesity, diabetes and
      tobacco smoking. The new challenge with the burden of diseases requires the
      implementation of a national strategy relevant to the epidemiological, social and
      economical transition. Population needs and cost effectiveness of interventions
      assessment is crucial to set the national priorities.

PMID- 16094844
TI  - [Cardiovascular disease surveillance in Tunisia].
AB  - OBJECTIVE: To assess the Cardiovascular risk factors trend in community based
      surveys. METHOD: Two population surveys were conducted in 1996-97 and 2000-01 in
      the Ariana region among 7608 adults 35-70 years aged. The surveys were based on:
      1--a questionnary, 2--an anthropometrical and physical examination, 3--a
      biological investigation, and 4--an ECG registration for the second cohort.
      RESULTS: Relative to the first survey, the prevalence of hypertension, diabetes,
      hypercholesterolemia didn't change significantly while borderline cholesterol
      increased on both genders, tobacco smoking decreased and ex-smokers increased on
      men. In both genders, hypertension and diabetes prevalence is low before 50 years
      but it increased after this age. Risk factors association is common: about 35%
      have more than two risk factors. This association is more common on women and
      diabetes-hypertension is the most frequent. CONCLUSION: These two surveys
      integrated in a global surveillance program has contributed to assess the CVDs
      burden and to identify priorities and intervention relevant to epidemiological
      region context.

PMID- 16094845
TI  - [Population surveillance of coronary heart disease].
AB  - OBJECTIVE: A cross-sectional population survey was carried out in the Ariana
      region in 2000-01. The aim of this study is to report the prevalence of CHD as
      indicated by ECG Minnesota coding. METHOD: A randomly selected sample included
      1837 adults 40-70 years. Data on socio-economic status, demographic, medical
      history, health behaviour, clinical and biological investigations were recorded.
      Risk factors (hypertension, dyslipedemia, obesity, diabetes) are defined
      according to WHO criterias. Standard supine 12 lead ECGs were recorded. All ECGs
      are red and classified according to the Minnesota codes criteria on CHD probable,
      CHD possible and on Major abnormalities and minor abnormalities. RESULTS: CHD
      prevalence was higher on women. Major abnormalities are more common on women
      (20.6% vs 13%), while minor abnormalities prevalence was higher on men (15.5% vs
      7.5%) (p<0.0001). The prevalence increased with age in both genders. CONCLUSION:
      This study tested how feasible is the population approach on CVDs surveillance.
      It highlighted the burden of cardiovascular diseases and support that women are
      at risk as men are. The value of ECG findings must be integrated in the
      cardiovascular diseases surveillance to identify high risk population.

PMID- 16094846
TI  - [Delays in acute myocardial infarction treatment: results of a multicenter study
      in the district of Tunis (Tunisia)].
AB  - OBJECTIVE: We aimed to assess the acute myocardial infarction management in Tunis
      public hospitals during one year (from March 2000 to February 2001). METHOD: A
      standard questionnaire was designed to record prospective data on 740 patients
      with a follow up during 28 days. Multivariate analysis was performed using the
      logistic regression model with all-factors as well as age, gender, CHD risk
      factors as predictors of the delay and fatality. 54% of patients were admitted
      during the first 6 hours after the onset of symptoms. In multivariate analysis,
      the delay of consultation is significantly correlated with gender (OR = 2.3, p <
      0.001), age (OR = 1.02, p < 0.01) and health insurance (OR = 1.5, p < 0.01). 90%
      of patients consulted in emergency wards. The emergency ambulance transported
      19.6% of patients. 48% of patients underwent early revascularisation of
      thrombolysis, 51% on men vs 31% on women (p < 0.01). The fatality rate was higher
      on women 14% vs 6.4% on men (p < 0.01) at 5 days and 27.2% vs 13.6% at 28 days.
      In multivariate analysis, the principal fatality predictive factor was age (RR =
      1.08, p < 0.001) and delay (2.56 p < 0.001) and tobacco smoking (RR = 2.83, p <
      0.0001). CONCLUSION: This study highlighted the problem of acute myocardial
      infarction management in public hospitals in Tunisia and it constitutes a
      baseline to assess different interventions focusing on cardiovascular diseases
      control and surveillance.

PMID- 16094847
TI  - [The cost of acute myocardial infarction management: the Tunisian experience].
AB  - OBJECTIVE: To assess the medical direct cost of acute myocardial infarction.
      METHOD: Data are recorded through a prospective study in 7 wards of cardiology of
      the District of Tunis during one year: from November 2001 to October 2002. Cost
      of hospital stay, biologic analyses, drugs, functional investigations and
      possible non surgical cardiologic intervention (IC) was calculated. RESULTS: 632
      AMI cases are recorded, the death rate is 7.8%. The average of hospital stay was
      13.3 days. 49.1% of patients benefited from thrombolytic therapy, 55.5% benefited
      from a coronary angiography and 16.1% of an act of IC. The mean of direct cost
      (CGM) was 2171 Tunisian Dinars and the median was 1731 DT, of whom room costs
      31.7%, 22.5% acts of IC, 7.2% drugs, 26.2% functional investigations and 12.4%
      biological analyses. The mean cost of IC was 3030 +/- 401 DT. CONCLUSION: The
      methodology of our study remains original in our country and can be used to
      assess the other aspects of AMI as other diseases cost management.

PMID- 16094848
TI  - [Secondary prevention of cardiovascular diseases: knowledge and practices of
      patients].
AB  - The aim of our study is to assess the degree of awareness and practices of
      patients with cardiovascular disease. METHOD: During October 2002-February 2003,
      we conducted a CAP study (Knowledge, attitudes, behaviors) at some outpatient
      clinic visit of Tunis District. Using a standardized questionnaire, investigators
      have collected demographic and personal data, informations about risk factor
      levels, knowledge and attitudinal characteristics related to risk factors for
      patients who satisfied the inclusion criteria. 443 patients have been interviewed
      (68.4% are men); 40% have more than 65 years old. Half of patients have never
      been schooled. Most of them have low socioeconomic level (38.8%) or middle one
      (56.0%). RESULTS: 66.9% of men have quit tobacco smoking and 19.5% still smoking
      41.3% of patients have some difficulties to change their lifestyle. The
      difference is statically significant by educational and occupational levels.
      Almost 60% of them used to practice daily moderate physical activity, which was
      more frequent among men then women (p<0.01). During the last year, majority of
      patients has had checked their blood pressure (98%), glycaemia (94%) and
      cholesterolemia (94%). However, about 57% to 67% of patients knew if they have
      hypertension, diabetes or hypercholesterolemia. Most of patients are aware that
      healthy lifestyle can be important in preventing heart attacks and stroke and
      that control of blood pressure, cholesterolemia and glycaemia reduce recurrence
      of these attacks once they happened. CONCLUSION: CVDs prevention and control is
      facing the crucial question on lifestyle change and enhancing patients
      responsibility in their own health promotion.

PMID- 16094849
TI  - [Social and occupational repercussions of acute myocardial infarction].
AB  - OBJECTIVES: The aim of this work was to study the family, social and occupational
      repercussions of acute myocardial infarction. MATERIAL AND METHODS: Our study
      concerns 70 patients less than 66 years old, working before their hospitalization
      and having been admitted for acute myocardial infarction between January 1st,
      1999 and December 31, 2000 in the Department of Cardiac Resuscitation of hospital
      La Rabta of Tunis. Data were collected from retrospective review of folders and
      answers to a questionnaire. RESULTS: There were 70 patients almost exclusively
      men (n=69). The mean age was 49.0 +/- 6.8 years. The mean follow-up was 27.2 +/-
      7.7 months. After the infarction, the majority of patients modified their
      activities (75.7%) notably their leisure activities (37.1%) and their travels
      (25.7%). Myocardial infarction had a bring about a bother in current life to
      50.0% of the patients, had an influence on emotional life of 41.4% and on sexual
      activities of 50.0% of the population. The direct repercussions of myocardial
      infarction on the professional capacities was observed in the majority of the
      patients. The average delay of return to work has been 91 +/- 111 days.
      CONCLUSION: Fight against the isolation of the patient and its exclusion by an
      adequate and early psychological coverage is the best way to assure the return in
      a normal family and professional life.

PMID- 16094850
TI  - [Hypertension prevalence, awareness, treatment and control: results from a
      community based survey].
AB  - The study objective was to assess the prevalence, level of awareness of
      treatment, and control of hypertension in a general population. We conducted a
      cross-sectional survey on 1837 adults 40-69 years old. Hypertension and control
      level are defined according to the WHO/ISH recommendations. HBP is defined as SBP
      > or = 140 and or DBP > or = 90 mm Hg and the use of blood pressure-lowering
      medication. Hypertension is controlled by medication if SBP < 140 and DBP < 90 mm
      Hg. We conduct analysis by socio demographic variable, medical history and CHDs
      risk factors. 44.3% of adults was hypertensive. The prevalence of hypertension
      was higher among women (48.2% versus 38.7% on men) and it increases in both
      genders with age, body mass index. Only 41% of the hypertensive were aware of
      having hypertension, among them, 74.1% declare that they are treated but only
      13.2% were controlled. The study highlights the problem of the hypertension in a
      developing country. It contributes to identify the huge iceberg of this CVDs risk
      factor. The national strategy must focus on the population life style and drugs
      management. The question is how much will be the cost of HBP and CVDs control for
      a country which has a limited resources.

PMID- 16094851
TI  - [Management of arterial hypertension: results of a Tunisian general practitioner
      survey].
AB  - The control of arterial hypertension (HT) is an endlessly hoped objective but
      usually not reached. Several factors are determinants. The physician role is
      crucial in the HT prevention. In order to evaluate knowledge, attitudes and
      behaviours of Tunisian physicians in HT management, we conducted a cross
      sectional study in 2002 using a self administered questionnaire addressed to
      physicians working in private and public sectors. 380 generalists participated to
      this study. 95.5% of them confirmed that HT constitutes a public health problem.
      81.1% saw at least 4 patients with HT a week. 95% insisted on the importance of
      the primary prevention. 90% took care themselves patients. 71.5% confirmed the
      importance of a training and an entrainement for the measure of the blood
      pressure (BP). 3.7% made diagnosis after a single visit and 10.9% confirmed it
      only from described symptoms. 20.4% of the generalists chose the old
      classification as objective level of BP. Thiazidic Diuretics and beta blockers
      were most prescribed medicines in first intention. 9.4% stopped the treatment
      after stabilization of blood pressure. 60% of generalists had inadequate
      behaviour facing a not stabilized BP. Non observance of treatment by patients was
      indicated by 31% of the generalists, cost and break of the medicines' stock and
      disappearance of symptoms were the main causes advanced by the generalists. This
      study shows the existence of gaps in generalists' practical behaviour treating
      this disease. Measures aiming the medical practice improvement turn out necessary
      in particular the sensitization of the generalists by an adequate university
      training and a continuous medical training, and a regular evaluation of the
      national program of hypertension prevention and management.

PMID- 16094852
TI  - Triacylglycerol oxidation in pig lipoproteins after a diet rich in oxidized
      sunflower seed oil.
AB  - The effects of two sunflower seed oil diets differing in oxidation levels (PV in
      oils 1 and 190 mequiv O2/kg) on lipoprotein TAG and total lipid oxidation were
      investigated in growing pigs. For 2 wk, two groups of 10 pigs were fed either of
      the diets, after which blood samples were collected. A method based on RP-HPLC
      and electrospray ionization-MS was used for the analysis of oxidized TAG
      molecules in chylomicrons and VLDL. The baseline diene conjugation method was
      used for the estimation of in vivo levels of lipoprotein lipid oxidation. TAG
      molecules with a hydroxy, an epoxy, or a keto group attached to a FA, as well as
      TAG core aldehydes were detected in the samples. Typically, lipoprotein TAG and
      total lipids were more oxidized in the pigs fed on the oxidized oil compared with
      those fed on nonoxidized oil. Oxidation of dietary fat was thus reflected in the
      lipoprotein oxidation, which confirmed our earlier findings.

PMID- 16094853
TI  - Changes in the milk and cheese fat composition of ewes fed commercial supplements
      containing linseed with special reference to the CLA content and isomer
      composition.
AB  - A study was carried out to increase the CLA contents in ewes' milk fat under
      field conditions by dietary means and to investigate the extent of the changes
      and consequences for milk processing and cheese quality. During a 3-mon period,
      ewes' bulk milk samples were collected every week from two different herds. For
      the first 4 wk the ewes were fed a conventional diet. Then the following 6 wk a
      supplement enriched in alpha-linolenate (whole linseed) was incorporated into the
      ovine diet. Finally, in the last 3 wk the feeding was the same as in the first 4
      wk. The FA profile in milk fat was monitored by GC, and the distribution of CLA
      isomers was thoroughly tested by combining GC-MS of 4,4-dimethyloxazoline
      derivatives (DMOX) with silver ion-HPLC (Ag(+)-HPLC) of FAME. Reconstructed mass
      spectral profiles of CLA characteristic ions from DMOX were used to identify
      positional isomers, and Ag(+)-HPLC was used to quantify them. An increase in
      total CLA in milk fat was observed, and total CLA remained elevated during the
      weeks of enriched alpha-linolenate feeding. In our experimental conditions there
      was a linear relationship between trans-vaccenic acid (trans-11-octadecenoic
      acid; trans-11 18:1) and 9-cis,11-trans CLA in ewes' milk fat. Concerning the CLA
      isomer profile, increases in the 11,13- and 12,14-18:2 positional isomers were
      considerable when linseed was included in the diet. Organoleptic characteristics
      of cheeses made with CLA-enriched milk did not substantially differ from those
      made with nonsupplemented ewes' milk. CLA total content and isomer profile did
      not change during ripening.

PMID- 16094854
TI  - Dietary fatty acids regulate cholesterol induction of liver CYP7alpha1 expression
      and bile acid production.
AB  - In the present study we investigated the effects of dietary fats containing
      predominantly PUFA, monounsaturated FA (MUFA), or saturated FA (SFA) on lipid
      profile and liver cholesterol 7alpha-hydroxylase (CYP7alpha1) mRNA expression and
      bile acid production in C57BL/6J mice. The animals (n = 75) were randomly divided
      into five groups and fed a basic chow diet (AIN-93G) (BC diet), a chow diet with
      1 g/100 g of cholesterol (Chol diet), a chow diet with 1 g/100 g of cholesterol
      and 14 g/100 g of safflower oil (Chol + PUFA diet), a chow diet with 1 g/100 g of
      cholesterol and olive oil (Chol + MUFA diet), or a chow diet with 1 g/100 g of
      cholesterol and myristic acid (Chol + SFA diet) for 6 wk. The results showed that
      the Chol + SFA diet decreased CYP7alpha1 gene expression and bile acid pool size,
      resulting in increased blood and liver cholesterol levels. Addition of PUFA and
      MUFA to a 1% cholesterol diet increased the bile acid pool production or bile
      acid excretion and simultaneously decreased liver cholesterol accumulation
      despite decreased CYP7alpha1 mRNA expression. The results indicate that the
      decreased bile acid pool size induced by the SFA diet is related to inhibition of
      the liver CYP7alpha1 gene expression, but an increased bile acid pool size and
      improved cholesterol homeostasis are disassociated from the liver CYP7alpha1 gene
      expression.

PMID- 16094855
TI  - Regulation of palmitoyl-CoA chain elongation by clofibric acid in the liver of
      Zucker fa/fa rats.
AB  - The regulation of palmitoyl-CoA chain elongation (PCE) by clofibric acid [2-(4
      chlorophenoxy)-2-methylpropionic acid] was investigated in comparison with
      stearoyl-CoA desaturase (SCD) in the liver of obese Zucker fa/fa rats. The
      proportion of oleic acid in the hepatic lipids of Zucker obese rats is 2.7 times
      higher than that of lean littermates. The activities of PCE and SCD in the liver
      of Zucker obese rats were markedly higher than in lean rats, and the hepatic
      uptake of 2-deoxyglucose (2-DG) was also higher in Zucker obese rats compared
      with lean rats. The increased activities of SCD and PCE in Zucker obese rats were
      due to the enhanced expression of mRNA of both SCD1 and rat FA elongase 2
      (rELO2), but not SCD2 or rELO1. The proportion of oleic acid in the liver was
      significantly increased by the administration of clofibric acid to Zucker obese
      rats, and the hepatic PCE activity and rELO2 mRNA expression, but not the SCD
      activity or SCD1 mRNA expression, were increased in response to clofibric acid
      treatment. By contrast, the activities of both PCE and SCD and the mRNA
      expression of SCD1 and rELO2 in the liver were increased by the treatment of
      Zucker lean rats with clofibric acid. Multiple regression analysis, which was
      performed to determine the relationships involving PCE activity, SCD activity,
      and the proportion of oleic acid, revealed that the three parameters were
      significantly correlated and that the standardized partial regression coefficient
      of PCE was higher than that of SCD. These results indicate that oleic acid is
      synthesized by the concerted action of PCE and SCD and that PCE plays a crucial
      role in the formation of oleic acid when Zucker fa/fa rats are given clofibric
      acid.

PMID- 16094856
TI  - A carbohydrate-rich diet reduces LDL size in QQ homozygotes for the Gln 192Arg
      polymorphism of the paraoxonase 1 gene.
AB  - Paraoxonase 1 (PON 1) is an esterase with antioxidant properties that is present
      in HDL. Gln192Arg polymorphism (also named Q192R or Q/R) of the PON 1 gene that
      encodes this protein defines two alleles (Q and R). The R allele has been
      associated with higher cardiovascular risk. LDL size and susceptibility to
      oxidation also have been identified as cardiovascular risk factors. Our objective
      was to determine whether genetic variations in the Gln192Arg polymorphism
      influence LDL size and susceptibility to oxidation after the consumption of diets
      with different fat content. In our experiments, the participants (n = 98)
      underwent three 4-wk diets--one, saturated fat-enriched (SAT); another,
      monounsaturated fat-enriched (MONO); and a third, carbohydrate-enriched (CHO). We
      observed that LDL were smaller in the QQ group after the CHO diet vs. the SAT (P
      < 0.01) and MONO diets (P < 0.03). No differences in LDL size were found in QR/RR
      subjects. When we analyzed lag time of oxidation of LDL, we found that when
      carriers of the R allele (QR/RR) received the MONO diet, the lag period of LDL
      oxidation was longer as compared with the CHO diet. Otherwise, we found no
      differences in QQ homozygotes when we evaluated the lag time of oxidation of LDL
      after the three diets. These results suggest that the Glnl92Arg polymorphism of
      the paraoxonase gene influences LDL size and susceptibility to oxidation in
      response to diet.

PMID- 16094858
TI  - Changes in phosphatidylcholine molecular species in the shrimp Macrobrachium
      borellii in response to a water-soluble fraction of petroleum.
AB  - The effect of the water-soluble fraction (WSF) of crude oil on lipid contents,
      lipid classes, FA, and PC molecular species was studied in high-phospholipid
      (hepatopancreas) and low-phospholipid (egg) tissues of a freshwater crustacean.
      After a 21-d exposure to a sublethal concentration of WSF, a significant decrease
      in shrimp total lipids was observed, although no alterations could be detected in
      the hepatopancreas or egg lipid contents. TAG/phospholipid ratios increased in
      the hepatopancreas and decreased in the eggs, suggesting alterations either in
      the mobilization of TAG to phospholipid pools or in the energy balance. The FA
      composition of phosphoglycerides in the hepatopancreas and eggs was dominated by
      PUFA, whereas the n-3/n-6 ratio was not affected by WSF exposure, although there
      was a significant increase in hepatopancreas 18:1n-9. Analysis of the PC
      molecular species by HPLC-ELSD showed the presence of 15 species, with 16:0/18:1,
      18:1/18:2, 16:0/20:5, and 16:1/20:5 being the major species in the
      hepatopancreas. The PC molecular species in the eggs showed a different pattern,
      dominated by 16:0/18:1 and 18:1/18:2. Of the PC molecular species, 10 contained
      22:6n-3, 20:5n-3, and 20:4n-6. Small amounts of di-PUFA species were also found.
      Exposure to WSF altered the PC molecular species in both tissues. The four major
      hepatopancreas molecular species and most of the ones containing PUFA decreased.
      This was compensated for by an increase in 16:1/18:1 (152%) and 18:1/18:1 (50%).
      The two major egg PC molecular species decreased, whereas the PUFA-containing
      ones increased. The contrasting responses of both tissues to WSF contamination
      suggests the presence of different homeostatic mechanisms.

PMID- 16094857
TI  - Effect of 18:1n-9, 20:5n-3, and 22:6n-3 on lipid accumulation and secretion by
      Atlantic salmon hepatocytes.
AB  - We have studied the effects of dietary FA on the accumulation and secretion of
      [3H]glycerolipids by salmon hepatocytes in culture. Atlantic salmon were fed
      diets supplemented with either 100% soybean oil (SO) or 100% fish oil (FO), and
      grew from an initial weight of 113 +/- 5 g to a final weight of 338 +/- 19 g.
      Hepatocytes were isolated from both dietary groups and incubated with
      [3H]glycerol in an FA-free medium; a medium supplemented with 0.75 mM of one of
      three FA-18:1 n-9, 20:5n-3, or 22:6n-3--or a medium supplemented with 0.75 mM of
      the sulfur-substituted FA analog tetradecylthioacetic acid (TTA), which cannot
      undergo beta-oxidation. Incubations were allowed to proceed for 1, 2, 6, or 24 h.
      The rate of the secretion of radioactive glycerolipids with no FA added was 36%
      lower from hepatocytes isolated from fish fed the FO diet than it was from
      hepatocytes isolated from fish fed the SO diet. Hepatocytes incubated with 18:1 n
      9 secreted more [3H]TAG than when incubated with no FA, whereas hepatocytes
      incubated with 20:5n-3 or TTA secreted less labeled TAG than when incubated with
      no FA. This observation was independent of the feeding group. Hepatocytes
      incubated with 22:6n-3 secreted the highest amounts of total [3H]glycerolipids
      compared with the other treatments, owing to increased secretion of phospholipids
      and mono- and diacylglycerols (MDG). In contrast, the same amounts of [3H]TAG
      were secreted from these cells as from cells incubated in an FA-free medium. The
      lipid-lowering effect of FO is thus independent of 22:6n-3, showing that 20:5n-3
      is the FA that is responsible for the lipid-lowering effect. The ratio of TAG to
      MDG in lipids secreted from hepatocytes to which 20:5n-3 or TTA had been added
      was lower than that in lipids secreted from hepatocytes incubated with 18:1 n-9
      or 22:6n-3, suggesting that the last step in TAG synthesis was inhibited.
      Morphometric measurements revealed that hepatocytes incubated with 20:5n-3
      accumulated significantly more cellular lipid than cells treated with 18:1n-9,
      22:6n-3, TTA, or no treatment. The area occupied by mitochondria was also greater
      in these cells. The present study shows that dietary FO reduces TAG secretion
      from salmon hepatocytes and that 20:5n-3 mediates this effect.

PMID- 16094859
TI  - Lipid composition influences the shape of human low density lipoprotein in
      vitreous ice.
AB  - Earlier cryo-electron microscopic studies have indicated that the normal low
      density lipoprotein (N-LDL) has a discoid shape when its core is in the liquid
      crystalline state. In the present study, we investigated whether the shape of LDL
      depends on the physical state and/or the lipid composition of the lipoprotein
      core. Using a custom-built freezing device, we vitrified NLDL samples from either
      above or below the phase-transition temperature of the core (42 and 24 degrees C,
      respectively). Cryo-electron microscopy revealed no differences between these
      samples and indicated a discoid shape of the N-LDL particle. In contrast, TG
      enriched LDL (T-LDL) did not have discoid features and appeared to be quasi
      spherical in preparations that were vitrified from either 42 or 24 degrees C.
      These results suggest that the shape of NLDL is discoid, regardless of the
      physical state of its core, whereas T-LDL is more spherical. Aspects that may
      influence the shape of LDL are discussed.

PMID- 16094860
TI  - Effects of droplet size on the oxidative stability of oil-in-water emulsions.
AB  - The effects of droplet size and emulsifiers on oxidative stability of
      polyunsaturated TAG in oil-in-water (o/w) emulsions with droplet sizes of 0.806
      +/- 0.0690, 3.28 +/- 0.0660, or 10.7 +/- 0.106 microm (mean +/- SD) were
      investigated. Hydroperoxide contents in the emulsion with a mean droplet size of
      0.831 microm were significantly lower than those in the emulsion with a mean
      droplet size of 12.8 microm for up to 120 h of oxidation time. Residual oxygen
      contents in the headspace air of the vials containing an o/w emulsion with a mean
      droplet size of 0.831 microm were lower compared with those of the emulsion with
      a mean droplet size of 12.8 microm. Hexanal developed from soybean oil TAG o/w
      emulsions with smaller droplet size showed significantly lower residual oxygen
      contents than those of the larger droplet size emulsions. Consequently, oxidative
      stability of TAG in o/w emulsions could be controlled by the size of oil droplet
      even though the origins of TAG were different. Spin-spin relaxation time of
      protons of acyl residues on TAG in o/w emulsions measured by H NMR suggested that
      motional frequency of some acyl residues was shorter in o/w emulsions with a
      smaller droplet size. The effect of the wedge associated with hydrophobic acyl
      residues of emulsifiers was proposed as a possible mechanism to explain
      differences in oxidative stability between o/w emulsions with different droplet
      sizes.

PMID- 16094861
TI  - Relative retention order of all isomers of cis/trans conjugated linoleic acid
      FAME from the 6,8- to 13,15-positions using silver ion HPLC with two elution
      systems.
AB  - CLA, defined as one or more octadecadienoic acids (18:2) with conjugated double
      bonds, has been reported to be active in a number of biological systems. GC and
      silver ion HPLC (Ag(+)-HPLC) have been the primary techniques for identifying
      specific CLA isomers in both foods and biological extracts. Recently, GC relative
      retention times were reported for all c,c, c/t (c,t and tc), and t,t CLA FAME
      from the 6,8- to the 13,15-positions in octadecadienoic acid (18:2). Presented
      here is the relative retention order of the same CLA FAME using Ag(+)-HPLC with
      two different elution systems. The first elution system, consisting of 0.1%
      acetonitrile/0.5% diethyl ether (DE)/hexane, has been used previously to monitor
      CLA composition in foods. Also presented here is the retention order of CLA FAME
      using 2% acetic acid/hexane elution solvent, which has advantages of more stable
      retention volumes and a complementary elution order of CLA FAME isomers. The data
      are reported using retention volumes (RV) adjusted for toluene, an estimator for
      dead volume, and relative to c9,t11-18:2. Measurement of relative RV in the
      analysis of 88 samples of cow plasma, milk, and rumen fluids using Ag(+)-HPLC is
      also presented here. The % CV ranged from 1.04 to 1.62 for t,t isomers and from 0
      to 0.48 for c/t isomers.

PMID- 16094862
TI  - Improved HPLC assay for lipid peroxides in human plasma using the internal
      standard of hydroperoxide.
AB  - We have developed a sensitive reversed-phase chemiluminescence HPLC approach for
      simultaneous quantitative and qualitative analyses of hydroperoxides of
      cholesteryl ester and TG in human plasma. Standard hydroperoxides of cholesteryl
      ester and TG and a novel internal standard (1-tetradecanyl 3-octadecenoyloxy
      5beta-cholan-24-oate monohydroperoxide) (I.S.) were chemically synthesized and
      the standard curves confirmed to be linear throughout the calibration range (1
      1000 pmol). Within-day and between-day CV were less than 7%, and the recoveries
      were within the range of 84-93%. With sample size minimized to 0.1 mL of plasma
      for each run, plasma cholesteryl ester hydroperoxide levels were 189 +/- 87 nM
      (mean +/- SD) in healthy young (22-25 yr old; n = 15, male/female = 6:9) and 210
      +/- 69 nM in healthy elderly (39-60 yr old; n = 6, male/female = 3:3). TG
      hydroperoxide was not detected in healthy subjects. In patients with advanced
      liver failure (36-67 yr old; n = 4, male/female = 2:2), hydroperoxide levels of
      plasma cholesteryl ester and TG were 11,903 +/- 9,553 nM and 3,318 +/- 1,590 nM,
      respectively, indicating an involvement of lipid oxidation. Sensitive and
      specific monitoring of plasma lipid peroxides using the present chemiluminescence
      HPLC approach with the synthesized I.S. may help our understanding of chemical
      and pathophysiological aspects of lipid peroxidation.

PMID- 16094863
TI  - Simultaneous quantification of free fatty acids, free sterols, squalene, and
      acylglycerol molecular species in palm oil by high-temperature gas chromatography
      -flame ionization detection.
AB  - This paper discusses a rapid GC-FID technique for the simultaneous quantitative
      analysis of FFA, MAG, DAG, TAG, sterols, and squalene in vegetable oils, with
      special reference to palm oil. The FFA content determined had a lower SE compared
      with a conventional titrimetric method. Squalene and individual sterols,
      consisting of beta-sitosterol, stigmasterol, campesterol, and cholesterol, were
      accurately quantified without any losses. This was achieved through elimination
      of tedious conventional sample pretreatments, such as saponification and
      preparative TLC. With this technique, the separation of individual MAG,
      consisting of 16:0, 18:0, and 18:1 FA, and the DAG species, consisting of the
      1,2(2,3)- and 1,3-positions, was sufficient to enable their quantification. This
      technique enabled the TAG to be determined according to their carbon numbers in
      the range of C44 to C56. Comparisons were made with conventional methods, and the
      results were in good agreement with those reported in the literature.

PMID- 16094864
TI  - Fatty acid composition of wild and farmed Atlantic salmon (Salmo salar) and
      rainbow trout (Oncorhynchus mykiss).
AB  - The goal of this study was to examine the FA composition of wild and farmed
      Atlantic salmon (AS) and rainbow trout (RT). FA profiles were obtained by GC/FID.
      Results showed that lipid and n-3 highly unsaturated FA contents of farmed and
      wild AS were similar. Total n-3 and n-6 PUFA were significantly higher in farmed
      AS than in wild AS. Farmed RT contained more fat and less n-3 PUFA than wild RT.
      Our results show that farmed salmonids provide high levels of n-3 HUFA to
      consumers.

PMID- 16094865
TI  - Enterocin AS-48RJ: a variant of enterocin AS-48 chromosomally encoded by
      Enterococcus faecium RJ16 isolated from food.
AB  - The bacteriocinogenic strain RJ16 isolated from goat cheese has been identified
      as Enterococcusfaecium by species-specific PCR, DNA-rRNA hybridization and rDNA
      sequencing. Purified bacteriocin from strain RJ16 is a carboxypeptidase A
      resistant peptide with a molecular mass (7125 Da) very close to the cyclic
      peptide enterocin AS-48. Bacteriocin from strain RJ16 and AS-48 show identical
      antibacterial spectra, although the former is slightly less active on strains of
      Listeria monocytogenes and Bacillus cereus. Producer strains show cross-immunity.
      PCR amplification of total DNA from strain RJ16 with primers for the AS-48
      structural gene and sequencing of the amplified fragment revealed an almost
      identical sequence (99.5%), except for a single mutation that predicts the change
      of Glu residue at position 20 of AS-48 to Val. Therefore, bacteriocin produced by
      E. faecium RJ16 should be considered a variant of AS-48, which we call AS-48RJ.
      PCR amplification revealed that strain RJ16 contains the complete as-48. gene
      cluster. Hybridization with probes for as-48 gene cluster revealed a chromosomal
      location of as-48 genes in strain RJ16, being the first example of a chromosomal
      location of this bacteriocin trait. Strain RJ16 produced enzymes of interest in
      food processing (esterase, esterase lipase and phytase activities), and did not
      decarboxylate amino acids precursors for biogenic amines. Strain RJ16 did not
      exhibit haemolytic or gelatinase activities, and PCR amplification revealed the
      lack of genes encoding for known virulence determinants (aggregation substance,
      collagen adhesin, enterococcal surface protein, endocarditis antigens, as well as
      haemolysin and gelatinase production). Strain RJ16 was resistant to ciprofloxacin
      (MIC > 2 mgl(-1)) and levofloxacin (MIC > 4 mgl(-1)) and showed intermediate
      resistance to nitrofurantoin and erythromycin, but was sensitive to ampicillin,
      penicillin, streptomycin, gentamicin, rifampicin, chloramphenicol, tetracycline,
      quinupristin/dalfopristin, vancomycin and teicoplanin. Altogether, results from
      this study suggest that this broad-spectrum bacteriocin-producing strain may have
      a potential use in food preservation.

PMID- 16094866
TI  - Mechanism of natural rifampin resistance of Streptomyces spp.
AB  - In a previous phylogenetic study of the genus Streptomyces using the rpoB gene,
      N531, which stands for an aspargine residue in position 531 of RpoB instead of
      serine (S531), known to be associated with natural rifampin resistance in several
      organisms, was also observed in the RpoB of several Streptomyces species. To
      determine whether N531 is associated with the rifampin resistance of Streptomyces
      strains, we analyzed the rifampin minimum inhibitory concentrations (MICs) of 11
      strains of the N531 RpoB type (putative rifampin resistant strains) and of 12
      strains of the S531 RpoB type. (putative rifampin susceptible strains). In
      general, the N531 RpoB types showed higher MIC levels (16-128 microg/ml) than the
      S531 RpoB types (0-8 microg/ml). To determine the isolation frequencies of N531
      RpoB types versus rifampin concentration, we applied screening methods involving
      different rifampin concentrations (0, 20 and 100 microg/ml) to Korean soils.
      Higher isolation frequencies of the N531 RpoB types were observed at the higher
      rifampin concentrations. In addition, during the course of this study we
      developed an allele specific PCR method to detect rifampin resistant Streptomyces
      strains. Our results strongly suggested that N531 might be involved in a major
      mechanism of natural rifampin resistance in strains of the genus Streptomyces.

PMID- 16094867
TI  - Characterization of Clostridium sp. RKD producing botulinum-like neurotoxin.
AB  - A Gram positive, motile, rod-shaped, strictly anaerobic bacterium isolated from
      intestine of decaying fish was identified as Clostridium sp. RKD and produced a
      botulinum type B-like neurotoxin as suggested by mouse bioassay and protection
      with anti botulinum antibodies. The neurotoxicity was functionally characterized
      by the phrenic nerve hemi-diaphragm assay. Phylogenetic analysis based on 16S
      rDNA sequence, placed it at a different position from the reported strains of
      Clostridium botulinum. The strain exhibited differences from both Clostridium
      botulinum and Clostridium tetani with respect to morphological, biochemical and
      chemotaxonomic characteristics. Botulinum group specific and serotype specific
      primers amplified the DNA fragments of 260 and 727 bp, respectively, indicating
      presence of botulinum type 'B' toxin gene. Sequence of nearly 700 bp amplified
      using primers specific for botulinum neurotoxin type B gene, did not show any
      significant match in the database when subjected to BLAST search.

PMID- 16094868
TI  - Caldimonas taiwanensis sp. nov., a amylase producing bacterium isolated from a
      hot spring.
AB  - During screening for amylase-producing bacteria, a strain designated OnlT was
      isolated from a hot spring located in Pingtung area, which is near the very
      southern part of Taiwan. Cells of this organism were Gram-negative rods motile by
      means of a single polar flagellum. Optimum conditions for growth were 55 degrees
      C and pH 7. Strain On1(T) grew well in minimal medium containing starch as the
      sole carbon source, and its extracellular products expressed amylase activity.
      The 16S rRNA gene sequence analysis indicates that strain On1(T) is a member of
      beta-Proteobacteria. On the basis of a phylogenetic analysis of 16S rDNA
      sequences, DNA-DNA similarity data, physiological and biochemical
      characteristics, as well as fatty acid compositions, the organism belonged to the
      genus Caldimonas and represented a novel species within this genus. The
      predominant cellular fatty acids of strain On1(T) were 16:0 (about 30%), 18:1
      omega 7c (about 20%) and summed feature 3 (16:1 omega 7c or 15:0 iso 2OH or both
      [about 31%]). Its DNA base ratio was 65.9 mol% G + C. We propose to classify
      strain On1(T) (= BCRC 17405T = LMG 22827T) as Caldimonas taiwanensis sp. nov.

PMID- 16094869
TI  - Alcaligenes faecalis subsp. phenolicus subsp. nov. a phenol-degrading,
      denitrifying bacterium isolated from a graywater bioprocessor.
AB  - A Gram (-) coccobacillary bacterium, J(T), was isolated from a graywater
      bioprocessor. 16S rRNA and biochemical analysis has revealed strain J(T) closely
      resembles Alcaligenes faecalis ATCC 8750T and A. faecalis subsp. parafaecalis DSM
      13975T, but is a distinct, previously uncharacterized isolate. Strain J(T), along
      with the type strain of A. faecalis and its previously described subspecies share
      the ability to aerobically degrade phenol. The degradation rates of phenol for
      strain J(T) and reference phenol degrading bacteria were determined by
      photometrically measuring the change in optical density when grown on 0.1% phenol
      as the sole carbon source, followed by addition of Gibb's reagent to measure
      depletion of substrate. The phenol degradation rates of strain J(T) was found to
      exceed that of the phenol hydroxylase group III bacterium Pseudomonas
      pseudoalcaligenes, with isolate J(T) exhibiting a doubling time of 4.5 h. The
      presence of the large subunit of the multicomponent phenol hydroxylase gene in
      strain J(T) was confirmed by PCR. The presence of the nirK nitrite reductase gene
      as demonstrated by PCR as well as results obtained from nitrite media indicated
      denitrification at least to N2O. Based on phenotypic, phylogenetic, fatty acid
      analysis and results from DNA DNA hybridization, we propose assigning a novel
      subspecies of Alcaligenes faecalis, to be named Alcaligenes faecalis subsp.
      phenolicus with the type strain J(T) (= DSM 16503) (= NRRL B-41076).

PMID- 16094870
TI  - DNA-based classification and sequence heterogeneities in the 16S rRNA genes of
      Lactobacillus casei/paracasei and related species.
AB  - The sequence differences within the 16S rRNA genes of Lactobacillus
      casei/paracasei and related species, Lactobacillus zeae and Lactobacillus
      rhamnosus, were investigated. Thirty-seven strains of mostly human or cheese
      origin were grouped by restriction endonuclease analysis (REA) of the total
      chromosomal DNA and by temporal temperature gradient gel electrophoresis (TTGE)
      of PCR-amplified 16S rRNA gene fragments. REA verified that all strains were
      genomically unique and singled out three major clusters, one L. rhamnosus-cluster
      and two clusters containing L. paracasei strains. The groups obtained by TTGE
      corresponded with one exception to the REA-clusters. In the TTGE clustering all
      L. paracasei strains formed one general group with one TTGE-band in common, and
      this group was sub-divided into five subgroups due to the presence of more than
      one TTGE-band in four of the subgroups. The occurrence of multiple TTGE-bands was
      investigated by amplifying and cloning of the 16S rRNA genes from the strains
      showing this phenomenon, thereby 12 clones from each strain were sequenced,
      demonstrating polymorphisms in almost all the cases. Subjecting the clones
      displaying sequence variations to TTGE as well as sequencing of 16S rDNA revealed
      by ribotyping of the strains, verified the presence of polymorphisms within the
      16S rRNA genes. The migration characteristic of amplified DNA from a single clone
      corresponded to a specific band in the TTGE-pattern of the strain from which the
      clone originated. Southern blot hybridisation with a 16S rDNA probe demonstrated
      the presence of at least five 16S rRNA genes in L. casei/paracasei. A higher
      degree of variable positions than previously reported was observed in the 16S
      rRNA gene fragments of the members in the complex. Sequence comparison between
      the 16S rRNA gene copies of L. casei (CCUG 21451T) and L. zeae (CCUG 35515T)
      demonstrated that the two species shared almost the same sequence in some copies
      while the others were more different. Our results provide one explanation for the
      difficulties in reaching clear-cut taxa within the L. casei/paracasei complex.

PMID- 16094871
TI  - Taxonomic comparison of three different groups of aflatoxin producers and a new
      efficient producer of aflatoxin B1, sterigmatocystin and 3-O
      methylsterigmatocystin, Aspergillus rambellii sp. nov.
AB  - Accumulation of the carcinogenic mycotoxin aflatoxin B, has been reported from
      members of three different groups of Aspergilli (4) Aspergillus flavus, A. flavus
      var. parvisclerotigenus, A. parasiticus, A. toxicarius, A. nomius, A.
      pseudotamarii, A. zhaoqingensis, A. bombycis and from the ascomycete genus
      Petromyces (Aspergillus section Flavi), (2) Emericella astellata and E.
      venezuelensis from the ascomycete genus Emericella (Aspergillus section
      Nidulantes) and (3) Aspergillus ochraceoroseus from a new section proposed here:
      Aspergillus section Ochraceorosei. We here describe a new species, A. rambellii
      referable to Ochraceorosei, that accumulates very large amounts of
      sterigmatocystin, 3-O-methylsterigmatocystin and aflatoxin B1, but not any of the
      other known extrolites produced by members of Aspergillus section Flavi or
      Nidulantes. G type aflatoxins were only found in some of the species in
      Aspergillus section Flavi, while the B type aflatoxins are common in all three
      groups. Based on the cladistic analysis of nucleotide sequences of ITS1 and 2 and
      5.8S, it appears that type G aflatoxin producers are paraphyletic and that
      section Ochraceorosei is a sister group to the sections Flavi, Circumdati and
      Cervini, with Emericella species being an outgroup to these sister groups. All
      aflatoxin producing members of section Flavi produce kojic acid and most species,
      except A. bombycis and A. pseudotamarii, produce aspergillic acid. Species in
      Flavi, that produce B type aflatoxins, but not G type aflatoxins, often produced
      cyclopiazonic acid. No strain was found which produce both G type aflatoxins and
      cyclopiazonic acid. It was confirmed that some strains of A. flavus var.
      columnaris produce aflatoxin B2, but this extrolite was not detected in the ex
      type strain of that variety. A. flavus var. parvisclerotigenus is raised to
      species level based on the specific combination of small sclerotia, profile of
      extrolites and rDNA sequence differences. A. zhaoqingensis is regarded as a
      synonym of A. nomius, while A. toxicarius resembles A. parasiticus but differs
      with at least three base pair differences. At least 10 Aspergillus species can be
      recognized which are able to biosynthesize aflatoxins, and they are placed in
      three very different clades.

PMID- 16094872
TI  - Enumeration of bacteria from the Clostridium leptum subgroup in human faecal
      microbiota using Clep1156 16S rRNA probe in combination with helper and
      competitor oligonucleotides.
AB  - Target site inaccessibility represents a significant problem for fluorescent in
      situ hybridisation (FISH) of 16S rRNA oligonucleotide probes. For this reason,
      the Clep1156 probe targeting 16S rRNA of the Clostridium leptum phylogenetic
      subgroup used for dot blot experiments could not be used until now for FISH.
      Considering that bacteria from the C. leptum subgroup are very abundant in the
      human faecal microbiota and may play a significant role in host health, we have
      used unlabelled helper and competitor oligonucleotides to improve the 16S rRNA in
      situ accessibility and specificity of the Clep1156 probe and applied this
      approach to enumerate C. leptum bacteria in this ecosystem. Nine C. leptum target
      strains and five non-target strains were selected to develop and validate the
      helper-competitor strategy. Depending on the target strains, the use of helpers
      enhanced the fluorescence intensity signal of Clep1156 from 0.4-fold to 8.4-fold
      with a mean value of 3.6-fold, switching this probe from the brightness class V
      VI (masked sites) to III-IV (accessible sites). The simultaneous use of helper
      and competitor oligonucleotides with Clep1156 probe allowed the expected
      specificity without disturbing in situ accessibility. Quantified by FISH combined
      with flow cytometry, C. leptum bacteria in human faecal samples (n=22)
      represented 19 +/- 7% of bacteria on average [4.9-37.5]. We conclude that helper
      oligonucleotides are very useful to circumvent the problem of target site in situ
      accessibility, especially when probe design is limited to only one 16S rRNA area
      and that helpers and competitors may be efficiently combined.

PMID- 16094873
TI  - Diverse rhizobia associated with woody legumes Wisteria sinensis, Cercis racemosa
      and Amorpha fruticosa grown in the temperate zone of China.
AB  - Fifty-nine bacterial isolates from root nodules of the woody legumes Wisteria
      sinensis, Cercis racemosa and Amorpha fruticosa grown in the central and eastern
      regions of China were characterized with phenotypic analysis, PCR-based 16S and
      23S rRNA gene RFLP, Box PCR and 16S rRNA gene sequencing. Seven main phena were
      defined in numerical taxonomy, which corresponded to distinct groups within the
      genera Agrobacterium, Bradyrhizobium, Mesorhizobium and Rhizobium in 16S and 23S
      rRNA gene PCR-RFLP. The phylogenetic relationships of the 16S rRNA genes
      supported the grouping results of PCR-RFLP. Most of the isolates from Amorpha
      fruticosa were classified into two groups closely related to Mesorhizobium
      amorphae. Seventeen of the 21 isolates from Wisteria sinensis were identified as
      two groups related to Rhizobium and Agrobacterium. Six out of 10 isolates from
      Cercis racemosa were identified as a group related to Bradyrhizobium. Our results
      indicated that each of the investigated legumes nodulated mainly with one or two
      rhizobial groups, although isolates from different plants intermingled in some
      small bacterial groups. In addition, correlation between geographic origin and
      grouping results was found in the isolates from Amorpha fruticosa. These results
      revealed that the symbiotic bacteria might have been selected by both the legume
      hosts and the geographic factors.

PMID- 16094874
TI  - Spatial distribution of organochlorine pesticide residues in soils surrounding
      Guanting Reservoir, People's Republic of China.

PMID- 16094875
TI  - Agricultural pesticides in groundwater of Kanchana Buri, Ratcha Buri, and Suphan
      Burl provinces, Thailand.

PMID- 16094876
TI  - Bioaccumulation of endosulfan from contaminated sediment by Vallisneria spiralis.

PMID- 16094877
TI  - Persistence of profenofos residue on tea under northeast Indian climatic
      conditions.

PMID- 16094879
TI  - Seasonal variation and spatial distribution of polycyclic aromatic hydrocarbons
      in atmospheric PM10 of Beijing, People's Republic of China.

PMID- 16094878
TI  - Distribution patterns of hexachlorocyclohexanes and other organochlorine
      compounds in muscles of fish from a Japanese remote lake during 2002-2003.

PMID- 16094880
TI  - Evaluation of fentrazamide for weed control and estimation of its residues in
      rice.

PMID- 16094881
TI  - Residual levels and bioaccumulation of chlorinated persistent organic pollutants
      (POPs) in vegetables from suburb of Nanjing, People's Republic of China.

PMID- 16094882
TI  - Environmental load of nitrogen and phosphorus from extensive, semiintensive, and
      intensive shrimp farms in the Gulf of California ecoregion.

PMID- 16094883
TI  - Followup study of mercury pollution in indigenous tribe reservations in the
      Province of Ontario, Canada, 1975-2002.

PMID- 16094884
TI  - Bioaccumulation of copper, iron, and zinc by Pinus halepensis (Miller).

PMID- 16094885
TI  - Removal of copper (VI) from aqueous solution by Ag/TiO2 photocatalysis.

PMID- 16094886
TI  - Nickel phytoremediation potential of broad bean, Vicia faba L., and its
      biochemical responses.

PMID- 16094887
TI  - Immobilization of heavy metals in contaminated soil using nonhumus-humus soil and
      hydroxyapatite.

PMID- 16094888
TI  - Application of various methods for assessment of background arsenic concentration
      in farming soil.

PMID- 16094889
TI  - Copper in livestock from polluted area.

PMID- 16094890
TI  - Possible involvement of oxidative stress in copper induced inhibition of nitrate
      reductase activity in Vallisneria spiralis L.

PMID- 16094891
TI  - Cytochrome B gene partial sequence and RAPD analysis of two Daphnia longispina
      lineages differing in their resistance to copper.

PMID- 16094892
TI  - Lack of evidence for metallothionein role in tolerance to copper by natural
      populations of Daphnia longispina.

PMID- 16094893
TI  - Toxicity of pendimethalin to nontarget soil organisms.

PMID- 16094894
TI  - Modulatory effect of cadmium injection on endosulfan-induced oxidative stress in
      the freshwater fish, Channa punctata Bloch.

PMID- 16094895
TI  - Gill modifications in the freshwater fish Cyprinus carpio after subchronic
      exposure to simazine.

PMID- 16094896
TI  - Toxicity testing with embryos of marine mussels: protocol standardization for
      Perna perna (Linnaeus, 1758).

PMID- 16094897
TI  - Application of microbiotests and activated sludge respirometry for the evaluation
      of industrial wastewater toxicity.

PMID- 16094898
TI  - New weaning recommendations: difficult to implement.

PMID- 16094899
TI  - School nurses and GPs: time to get together.

PMID- 16094900
TI  - A multiprofessional children's feeding clinic.
AB  - A paediatric dietitian, occupational therapist and speech and language therapist
      describe how they jointly run a feeding clinic for infants and children with
      feeding difficulties. Conditions treated include cerebral palsy, autism, learned
      aversion following severe gastro-oesophageal reflux, and delayed oral development
      that affects feeding. The therapists' co-ordinated approach enables parents to
      receive clear guidance on feeding at one combined appointment, without the
      inconvenience of having to attend three separate appointments. The article
      outlines the role of each therapist, with examples of how they assess and
      alleviate the children's problems. The need for safety, nutrition and hydration
      is balanced against the desire for developmental progress in a holistic approach
      involving all three therapy disciplines. The aim of the feeding clinic is to
      provide advice, support and intervention plans to help make feeding a pleasurable
      and safe experience for all the children who attend.

PMID- 16094901
TI  - Weight management in primary care: the Counterweight Project.
AB  - Obesity is a serious public health problem in the UK and needs to be tackled both
      at an environmental and an individual patient level. The Counterweight Project is
      a structured general practice programme and the first large-scale practice nurse
      led intervention aimed at improving the management of obesity in primary care.
      Preliminary results suggest 40% of patients completing the weight management
      aspect of the programme achieve and maintain a 5% loss of initial body weight at
      12 months. The project is led by a board of consultants from across the UK, is
      facilitated by dietitians and involves 80 general practices.

PMID- 16094902
TI  - Conference round-up: Breast-feeding, ADHD and sleep problems in children.

PMID- 16094903
TI  - Nutrition for toddlers: the foundation for good health--2. Current problems and
      ways to overcome them.
AB  - Part 2 of a two-part review of toddler nutrition considers some current concerns,
      including the influence of changing lifestyles on dietary patterns; dietary
      imbalances; obesity; and iron deficiency anaemia. The review includes some
      practical steps to prevent obesity and iron deficiency anaemia.

PMID- 16094904
TI  - Liquid based cytology: a new cervical screening system for the UK.
AB  - Liquid based cytology is replacing the traditional Pap smear as the method of
      screening for cervical cancer in the UK. This article discusses liquid based
      cytology, the implementation programme and other developments in screening for
      cervical cancer.

PMID- 16094905
TI  - Serum albumin in Down Syndrome with and without Alzheimer's Disease.
AB  - AIMS: We investigated whether or not serum albumin concentrations in Down
      Syndrome were lower than those of a cohort of similarly moderately- to-severely
      disabled institutionalised patients without Down Syndrome and, if so, whether or
      not this could be ascribed to the presence of liver disease. We also sought to
      determine the influence of Down Syndrome, age, liver disease, and Alzheimer's
      Disease on the serum albumin concentration. METHODS: We performed a cross
      sectional study on 205 institutionalised patients with Learning Disabilities (47
      with Down Syndrome, 158 without), and used multiple regression techniques to
      determine the relative effects of age, liver disease, and the presence or absence
      of Down Syndrome on the serum albumin concentration. Among Down Syndrome
      patients. We also sought to determine the association between serum albumin
      concentration and the presence of Dementia of Alzheimer's Type. RESULTS: Down
      Syndrome patients had lower serum albumin levels than non-Down Syndrome patients.
      Serum albumin concentrations declined with age at a similar rate in both groups,
      such that the effect on serum albumin of having Down Syndrome was equivalent to
      an additional 44 years of age. The serum albumin concentration in Down Syndrome
      patients with Alzheimer's Disease was greater than that in Down Syndrome patients
      without Alzheimer's Disease. CONCLUSIONS: Down Syndrome is associated with a low
      serum albumin concentration, independently of the presence of liver disease. The
      advent of Alzheimer's Disease in Down Syndrome is not associated with a further
      fall, and may be associated with a rise, in serum albumin concentrations.

PMID- 16094906
TI  - Renal transplantation in the elderly--the Irish experience.
AB  - BACKGROUND: The aim of this paper was to evaluate patient and kidney graft
      survival rates in renal transplant recipients and compare the outcomes between
      the different patient age groups. METHODS: A retrospective review of all adult
      renal transplants performed at Beaumont Hospital between the years 1986-2001 was
      carried out. Patients were defined as 'elderly' if they were 65 years of age or
      older and 'younger' if less than 65 years at the time of transplantation. Patient
      and transplant graft survival rates were analysed for each age group. RESULTS:
      Data were analysed on 1462 'younger' patients and 105 'elderly' renal transplant
      recipients. Estimated patient survival at 1, 5 and 10 years were 96%, 87% and 74%
      in the younger patient group compared to 85%, 59% and 33% in the elderly group.
      The adjusted graft survival rates (adjusted for death due to other causes and
      with a functioning graft in situ) for the younger group were 89%, 77% and 64% at
      one, five and ten years respectively, while for the elderly group, adjusted one,
      five and ten year survival rates were 89%, 83% and 70% respectively. CONCLUSIONS:
      Although the elderly have a shorter life expectancy than the younger population
      they do benefit from renal transplantation similar to the younger recipients.

PMID- 16094907
TI  - Bloodborne virus infections among drug users in Ireland: a retrospective cross
      sectional survey of screening, prevalence, incidence and hepatitis B immunisation
      uptake.
AB  - BACKGROUND: Injecting drug users are at high-risk of bloodborne virus infections
      including hepatitis C (HCV), hepatitis B (HBV) and HIV. AIMS: To document
      screening for and immunisation against bloodborne viruses and to determine the
      known prevalence and incidence of these infections. METHODS: A cross-sectional
      survey of clients attending 21 specialist addiction treatment clinics in one
      health board area in greater Dublin. Data collected on demographic
      characteristics, serology for HCV, HBV and HIV and immunisation against HBV.
      RESULTS: A total of 316 (88%) had been tested for anti-HCV antibody, 244 (68%)
      had been tested for anti hepatitis B core antibody (anti-HBc), 299 (84%) had been
      tested for hepatitis B surface antigen (HBsAg) and 307 (86%) had been tested for
      anti-HIV antibody. The prevalence of anti-HCV, anti-HBc, HBsAg, and anti-HIV
      were: 66%, 17%, 2% and 11% respectively. The incidence of HCV, HBV and HIV
      infections were: 24.5, 9.0 and 3.4 per hundred person years respectively. Eighty
      one per cent of those in whom it was indicated, had started a targeted HBV
      immunisation programme in the clinics. CONCLUSION: The proportion of clients
      screened for HCV, HBV and HIV infection has increased since the introduction of a
      screening protocol in 1998. Targeted vaccination for opiate users against
      hepatitis B is more successful than previously shown in Ireland. The prevalence
      and incidence of bloodborne viruses remains high among opiate users attending
      addiction treatment services, despite an increase in availability of harm
      reduction interventions.

PMID- 16094908
TI  - Health-related quality of life during four-layer compression bandaging for venous
      ulcer disease: a randomised controlled trial.
AB  - BACKGROUND: Venous leg ulceration is a chronic debilitating condition which
      negatively impacts on patients' quality of life. Despite the application of gold
      standard treatment a number of patients suffer from 'slow to heal' ulcers, which
      can require treatment for years. AIMS: The aim of this study was to compare the
      effects of four-layer compression bandaging (4LB) for treating venous leg ulcers
      with other available treatments on health-related quality of life
      duringtreatment. METHODS: In this pragmatic trial, 200 patients with venous leg
      ulceration were randomised either to 4LB (intervention group; n = 100) or to
      continue their usual system of care (control group; n = 100). Analysis was by
      intention to treat; quality of life measurements were taken at randomisation and
      after six weeks of treatment. RESULTS: 4LB provided greater quality of life
      benefits than the control group particularly in the area of physical activity and
      social functioning. CONCLUSION: Due to the long-term nature of treatment for many
      of these patients, the effects on quality of life should be considered when
      prescribing treatment. This study has shown that 4LB significantly improves the
      quality of life of patients during treatment for venous leg ulceration.

PMID- 16094909
TI  - Autologous stem cell transplantation in myeloma: the St James's Hospital
      experience, 1997-2003.
AB  - BACKGROUND: High-dose treatment with autologous stem cell transplantation (ASCT)
      has become the standard of care for patients with myeloma below the age of 65
      years. AIMS: We report an audit of 60 patients (median age: 52.5 years) who
      underwent ASCT in the National Bone Marrow Transplant centre in St James's
      Hospital in Dublin between 1997 and 2003 inclusive. METHODS: Clinical and
      laboratory data were retrieved from patient medical records and hospital
      information management systems. RESULTS: Thirty-six patients had IgG, 11 IgA, 1
      IgD, 9 light chain and 3 non-secretory MM. Fifty-seven (95%) patients received
      anthracycline-corticosteroid combination chemotherapy prior to autografting.
      There was no transplant-related mortality (TRM). Complete (CR) and Partial
      Responses (PR) were seen in 16 (29.6%) and 29 (53.7%) of those evaluable (n = 54
      (90%)). The actuarial Progression-Free (PFS) and Overall Survival (OS) rates at
      five years are 13% and 55% respectively. CONCLUSION: Centre outcome is comparable
      to published international series and supports the use of ASCT in the treatment
      of this malignancy.

PMID- 16094910
TI  - Changing trends in the management of infantile hypertrophic pyloric stenosis--an
      audit over 11 years.
AB  - BACKGROUND: This article is a follow-up to an audit performed by the Department
      of Surgery and published in the Irish Journal of Medical Science in 1996. This
      audit reviewed all cases of Infantile Hypertrophic Pyloric Stenosis (IHPS)
      operated on over 22 years up to 1991. AIMS: We aim to demonstrate that radiologic
      investigations, namely barium meal and ultrasound, have been increasingly
      employed in the diagnosis of IHPS. In addition, ultrasound is now the
      investigation of choice. METHODS: We have reviewed all cases of IHPS, at the same
      institution, over the subsequent 11 years, with reference to any radiological
      investigations performed. In the previous study, the diagnosis of IHPS was made
      clinically in 92.6% with the remainder diagnosed radiologically. RESULTS: Over 11
      years, 157 patients were diagnosed with IHPS. Male to female ratio was 4.06:1.
      Median age was four weeks (range 1-18 weeks).Twenty-four per cent had a barium
      meal, 36% had an ultrasound and 13% had both performed. CONCLUSION: We conclude a
      change in practice in the management of IHPS with radiology, particularly
      ultrasound, playing an increasing role.

PMID- 16094911
TI  - Trends in ophthalmic surgery in Ireland.
AB  - AIMS: This study was designed to document the changing trends in ophthalmic
      surgery in acute public hospitals in the Republic of Ireland over the years 1994
      to 2001. METHOD: We obtained Hospital In-Patient Enquiry (HIPE) data returned
      from the major acute public hospitals to the Economic and Social Research
      Institute. We searched for cataracts, glaucoma, retinal detachment, strabismus,
      corneal transplant and repair of perforating injuries of the globe. RESULTS:
      There was a 24% increase in the total number of the searched operations occurring
      during the study period, from 8,857 procedures in 1994 to 11,005 in 2001. In
      2001, cataract surgery alone counted for 82% of all procedures performed. There
      was a large increase in cataract (49%) and vitreo-retinal procedures (41%)
      reported between 1994 and 2001. Conversely, a large fall in trabeculectomy (67%),
      strabismus (63%) and corneal transplant (52%) procedures occurred during the
      study period. CONCLUSION: These data suggest that surgical numbers in
      ophthalmology in Ireland are increasing and the relative proportions are
      changing.

PMID- 16094912
TI  - Using HIPE data as a research and planning tool: limitations and opportunities.
AB  - BACKGROUND: The Hospital Inpatient Enquiry (HIPE) system is an important
      information source for research and health service planning activities. However,
      as it was not designed explicitly for these purposes, some limitations exist.
      AIMS: To make recommendations that would increase the value of HIPE as a research
      and planning tool. METHODS: Experiences of using HIPE for research and planning
      exercises were analysed so as to identify its limitations and their impact on
      research and planning. RESULTS: Limitations were identified regarding data
      quality, policy issues and the general system. CONCLUSIONS: To increase the
      utility of HIPE as a research and planning tool, a number of changes are
      recommended, including: expanding the system to cover private hospitals and
      outpatient and emergency services; adopting routine small area and socio-economic
      coding; adopting unique personal identifiers; publishing regular detailed reports
      with in-depth analyses; and considering making hospital identifiers available in
      certain circumstances.

PMID- 16094915
TI  - Small bowel obstruction secondary to a giant enterolith complicating Crohn's
      disease.
AB  - BACKGROUND: Enterolith formation associated with Crohn's disease is a very
      uncommon clinical entity. AIM: To describe a case of sub-acute small bowel
      obstruction secondary to a giant enterolith in a patient with Crohn's disease.
      RESULTS: A 54-year-old male with a history of Crohn's disease presented with sub
      acute small bowel obstruction secondary to a giant enterolith. The diagnosis was
      confirmed utilising plain film radiography and computed tomography CONCLUSION:
      Plain film radiography and computed tomography play a central role in
      establishing the diagnosis of this rare complication of Crohn's disease and
      assist in planning surgical intervention.

PMID- 16094913
TI  - Relating undergraduate musculoskeletal medicine curricula to the needs of modern
      practice.
AB  - BACKGROUND: International studies have demonstrated significant discrepancies
      between undergraduate musculoskeletal curricula and the needs of modern medical
      practice. AIMS: To determine the prevalence of musculoskeletal disorders in
      primary care, General Practitioners, assessment of their undergraduate
      musculoskeletal training and that considered ideal for several clinical skills,
      and the relative importance of the ability to recognise selected clinical
      presentations. METHODS: A postal survey of 200 General Practitioners using a
      detailed questionnaire. RESULTS: The response rate was 50.5%, with respondents
      being an average 18.5 years in practice. They saw a mean 140.3 patients/week
      (range 10-270) of which 17.4% presented with musculoskeletal complaints (range 5
      50%). Respondents felt their musculoskeletal education was poor, with a
      significant difference between it and their ideal (p = 0.007). The most important
      skill for a graduating doctor was history taking, examination and appropriate
      investigation of a musculoskeletal problem. The most important clinical
      presentation was recognition of traumatic quadriplegia. CONCLUSIONS: A large
      proportion of primary care in Ireland is devoted to musculoskeletal complaints,
      however, there are deficiencies perceived in undergraduate musculoskeletal
      education. A review of undergraduate musculoskeletal curricula, emphasising the
      clinically relevant aspects of this discipline is needed.

PMID- 16094916
TI  - Giant solitary non-parasitic cyst of the liver.
AB  - BACKGROUND: Cystic diseases of the liver and intrahepatic biliary tree are
      uncommon. The majority of cases are detected only when patients become
      symptomatic, or as an incidental finding on radiological imaging. METHODS: We
      discuss the case of a 25-yr-old female with a centrally located giant liver cyst
      causing obstructive jaundice, and briefly discuss the management options in the
      treatment of this uncommon problem. RESULTS AND CONCLUSIONS: Intervention is
      recommended in patients with symptomatic simple cysts of the liver. Surgical
      cystectomy is the treatment of choice for large deep seated cysts.

PMID- 16094917
TI  - Massive retroperitoneal ganglioneuroma presenting with small bowel obstruction 18
      years following initial diagnosis.
AB  - BACKGROUND: Ganglioneuroma is a rare tumour of neural crest origin, which arises
      from maturation of a neuroblastoma. While previously considered to be non
      functioning, they are now known to be frequently endocrinologically active. AIMS
      AND METHODS: We report a case of a massive retroperitoneal ganglioneuroma
      presenting with small bowel obstruction in an adult, 18 years after initial
      diagnosis. Urinary dopamine levels were elevated, but other catecholamines were
      within normal limits. This is the first report in the English-language literature
      of a retroperitoneal ganglioneuroma presenting with or causing intestinal
      obstruction. We also review the metabolic, radiological, and histological
      features of these tumours. Relevant publications were identified from a Medline
      search using the MeSH headings 'ganglioneuroma', 'retroperitoneal neoplasms' and
      'intestinal obstruction', and also from the reference lists of retrieved
      articles. CONCLUSIONS: Ganglioneuroma can grow to a massive size and present in a
      varied manner. It should be included in the differential diagnosis of any large
      retroperitoneal or mediastinal mass, including those causing bowel obstruction.

PMID- 16094918
TI  - The rise of Troponin.

PMID- 16094919
TI  - Eureka! Osteoporosis diagnosed!

PMID- 16094920
TI  - Policy and politics.

PMID- 16094922
TI  - Nothing to declare.

PMID- 16094921
TI  - Relative merits of the single and triple MMR vaccines.

PMID- 16094923
TI  - Making it better: children's place in sustainable development.

PMID- 16094924
TI  - Healthcare in 'God's own country', Kerala, South India.

PMID- 16094925
TI  - Better hospital food project: success or failure?

PMID- 16094926
TI  - Obesity: pathophysiology and treatment.
AB  - Obesity appears to be a growing trend which is independent of age. Several
      associations have been made with respect to its onset, but as yet these
      associations remain subjective. This article reviews obesity, its pathophysiology
      and treatment. Dietary and behavioural modification and physical exercise are the
      main forms of treatment for many obese individuals. Pharmacological therapy is a
      second option.

PMID- 16094927
TI  - A catastrophe in the 21st century: the public health situation in South Africa
      following HIV/AIDS.
AB  - During the early 1900s, African populations in South Africa were subject to very
      widespread infections which especially affected the young. This resulted in high
      mortality rates and a low life expectancy of 20-25 years. By the mid-century,
      mortality rates from infections had decreased considerably. Moreover, the
      occurrences of non-communicable diseases, even in urban areas, remained very low.
      In the 1970s, the proportion of Africans aged 50 or over that reached 70 years
      was 38.5%, higher than that in the juxtaposed white population, which was 35.5%.
      And by 1985, the life expectancy of Africans reached 61 years for males and 63
      years for females, probably the highest in sub-Saharan African populations. Since
      then, however, the African continent has been devastated by the AIDS epidemic. In
      2001, HIV was responsible for the death of a third of the African population in
      South Africa, but even higher proportions prevailed in Botswana and in Tanzania.
      The calamitous advent of the HIV infection has caused major falls in life
      expectancy, in the case of Africans in South Africa reducing this to just 43
      years. With little hope of meaningful changes occurring in sexual habits or of an
      early vaccine becoming available, the infection's high morbidity/mortality burden
      is likely to continue.

PMID- 16094928
TI  - Allergic rhinitis: an update.
AB  - Allergic rhinitis is extremely common and a global health problem. One study has
      quoted a prevalence of 16% and, as with asthma, it seems to be increasing. This
      increase and association with asthma have raised concerns about appropriate
      treatment. Fortunately, with new knowledge of the pathophysioLogic mechanisms,
      newer and better treatment strategies have been developed. This short review of
      allergic rhinitis highlights its prevalence, pathophysiology, clinical
      presentation, investigation and management. A new classification and
      recommendations by the World Health Organization's guidelines 'Allergic Rhinitis
      and its Impact on Asthma' are also discussed.

PMID- 16094929
TI  - Overactive bladder.
AB  - Overactive bladder (OAB) is defined as urgency, with or without urge
      incontinence, usually with frequency and nocturia, in the absence of local
      pathological or hormonal factors. It is a common complaint of men and women
      alike, with estimates of 22 million sufferers. ApproximateLy 70% of men with
      bladder outflow obstruction will have some symptoms of OAB. The exact
      pathophysiology of OAB in bladder outflow obstruction is yet to be elucidated;
      evidence to date points to changes in both the efferent and afferent innervation
      and the detrusor. Management of OAB can be is generally with pharmacological
      agents such as anticholinergics or operative measures such as the 'Clam'
      cystoplasty. More recent treatment modalities include intravesicaL oxybutynin,
      intradetrusor botulinum toxin and neuromodulation. More specific treatment
      options for OAB in bladder outflow obstruction include relief of the obstruction
      with surgical (e.g. transurethraL resection of prostate) or pharmaceutical (e.g.
      a blockers) methods.

PMID- 16094930
TI  - Investigation into different skin conditions in certain occupations.
AB  - The aim of this study was to establish whether those working in certain
      occupations had skin with a Lower moisture content than would be considered
      normaL. Skin moisture levels were measured as well as visual assessment. Results
      indicated that all occupational groups studied had skin that was less well
      hydrated than would be considered normal, although there were significant inter
      individual variations within any one group. These variations were at least as
      significant as occupation. Awareness of the need to use gloves as protection
      against chemicals and to use emollients to restore condition was low, as was
      compliance.

PMID- 16094931
TI  - Prevalence of STI/HIV co-infections among special treatment clinic attendees in
      Ibadan, Nigeria.
AB  - Sexually transmitted infections (STIs) are poorly recognised and inadequately
      treated in Nigeria despite the fact that they constitute a major risk factor for
      sexual transmission of HIV infection. This study was carried out to ascertain
      STI/HIV co-infection rates and also to obtain relevant socio-demographic and
      reproductive health data associated with STI/HIV infections among special
      treatment clinic (STC) attendees. This information is urgently needed for
      designing STI/HIV control strategies. All consenting patients who attended the
      STC clinic from March to November 2001 were interviewed to obtain their socio
      demographic and reproductive health data. Urethral, high vaginal and endocervical
      swabs and urine specimens were obtained and processed by standard methods. HIV
      screening was done by double ELISA tests. Of the 210 patients seen, 98 (46.7%)
      were male and 112 (53.3%) were female (p > 0.05). The majority, 171 (81.4%) were
      aged 20-39 years, while only ten (4.8%) were adolescents. One-hundred-and-eighty
      (85.7%) had an STI, of which 41 (22.8%) were co-infected with HIV. Thirty (16.7%)
      patients with nongonococcal urethritis/cervicitis and five (2.8%) with gonorrhoea
      were also positive for HIV. Five patients were HIV positive but had no other STI.
      Patients with gonorrhoea, non-gonococcal urethritis/cervicitis, trichomoniasis
      and bacterial vaginosis were more likely than those with warts, candidiasis and
      herpes to have co-infection (chi2 = 12.5, p = 0.04). The study's HIV prevalence
      rate was 21.9%. STI/HIV co-infection rate was significantly higher among
      unskilled and unemployed patients compared with professional and skilled workers
      (p < 0.05). This study shows a high STI/HIV co-infection rate indicating that
      there is need for proper management of STI, as this will help curb the spread of
      HIV infection in Nigeria.

PMID- 16094933
TI  - Can quality software put your patients in danger?

PMID- 16094932
TI  - A problem with JCR software sets off alarm bells at organizations.

PMID- 16094934
TI  - Are your data collection efforts getting results?

PMID- 16094935
TI  - Surveyors want to see patient safety culture.

PMID- 16094936
TI  - A quality information system 'wish list'.

PMID- 16094937
TI  - [Transposition].

PMID- 16094938
TI  - [The dynamics of morphological changes in the terminal network of blood vessels
      in the mucosa of the lower lip affected by pre-canceroses or carcinoma. Part 1.
      Terminal blood capillary network in the mucosa of the mouth and lip in healthy
      and affected patients].

PMID- 16094939
TI  - [Juvenile melanoma of the palate].

PMID- 16094940
TI  - [Dental extractions and postextraction complications. Analysis of causes].

PMID- 16094941
TI  - [Analysis of jaw injuries treated in the years 1960-1964 in the Stomatological
      Clinic in Plzen].

PMID- 16094943
TI  - [Bone saw suitable for stomatosurgical operations].

PMID- 16094942
TI  - [Gingival fibroma with central ossification].

PMID- 16094944
TI  - [Cavernous hemangioma in the oral cavity].

PMID- 16094945
TI  - [Is the microbial invasion in radiation disease and in jaw fractures the main
      cause of the enhanced malignity of these injuries?].

PMID- 16094946
TI  - [Tumour of the jaw by fibrous osteodysplasia].

PMID- 16094947
TI  - [Contribution to the traumatic lesions of dental germs].

PMID- 16094948
TI  - [Importance of exfoliative cytology in stomatology].

PMID- 16094949
TI  - [A rare case of congenital cyst of the floor of the mouth].

PMID- 16094950
TI  - [Predilection sites for caries. II. Caries in fissures and pits].

PMID- 16094951
TI  - [The effect of same devitalization agents on cells in tissue cultures. Study in
      phase contrast microscope].

PMID- 16094952
TI  - [Devitalization by paraformaldehyde].

PMID- 16094953
TI  - [The effectivity of chemical compounds used for the enlargement of root canals].

PMID- 16094954
TI  - [The possibility of filling root canals with the aid of magnetodynamic action.
      Preliminary report].

PMID- 16094955
TI  - [Histological control of the periapical tissue after root canal filling].

PMID- 16094956
TI  - [Comments on the treatment of a lingual crossbite of upper incisors].

PMID- 16094957
TI  - [An attempt to influence the postoperative course by Ketazon Spofa. (Clinical
      trial)].

PMID- 16094958
TI  - [Observations on the tuberculous inflammations of lymph nodes in the orofacial
      region ].

PMID- 16094959
TI  - [The study of the level of labelled procain C14 in the body of the guinea pig
      with special concern of its distribution in the brain].

PMID- 16094960
TI  - [The present state of chemical devitalization of the dental pulp. A review].

PMID- 16094961
TI  - [Caries predilection sites. III. Cervical caries ].

PMID- 16094962
TI  - Excision of pyrimidine dimers by several UV-sensitive mutants of S. pombe.
AB  - Nine radiation-sensitive mutants of S. pombe showing a variety of phenotypic
      characteristics were analysed for their ability to excise pyrimidine dimers after
      ultraviolet irradiation. From earlier studies using indirect parameters, it was
      expected that some would be excision-deficient. Data reported here show that all
      the mutants tested, like wild type cells, were able to remove a high percentage
      of pyrimidine dimers during post-irradiation incubation in several different
      holding media, but not in saline or phosphate buffer. These mutants included
      strains showing increased, as well as others which showed decreased, levels of UV
      induced mutation frequency relative to that of the wild type at the same total
      dose.

PMID- 16094963
TI  - Genetic and enzymic studies on the recombination process in Bacillus subtilis.
AB  - We have isolated recombination deficient mutants of Bacillus subtilis on the
      basis of their sensitivity to methyl-methane-sulfonate or ultraviolet light, or
      of their inability to be transformed on solid medium. We have analyzed the
      mutants for several recombination and repair properties; we have grouped them in
      5 classes on the basis of their phenotype and tested them for the activity of
      several enzymes acting on DNA, ie. DNA polymerase, polynucleotide ligase, ATP
      dependent DNase, and a DNase acting on single-stranded DNA. One mutant was found
      reduced in the latter DNase. Some of the mutants have been mapped, and they
      correspond to three different genes denominated rec D, rec F and rec G. All the
      recombination deficient mutants of B. subtilis described in the literature have
      been grouped in 7 classes; the mutations belong to 13 (and possibly 15) different
      genes distributed along the map. A coherent nomenclature and the criteria for a
      standard study of the rec mutants are proposed.

PMID- 16094964
TI  - Temperature-sensitive, osmotic-remedial mutants of Neurospora crassa: osmotic
      pressure induced alterations of enzyme stability.
AB  - Three temperature-sensitive, adenine-requiring mutants of Neurospora crassa were
      found to be osmotic-remedial when non-penetrating solutes were used to increase
      the osmolarity of the growth medium. The affected enzyme (adenylosuccinase) from
      one of the mutants (ad-4, 44206t) was found to have higher levels of activity
      when the organism was grown at non-permissive temperatures under osmotic-remedial
      conditions than when it was grown with adenine as a nutritional supplement. The
      enzyme synthesized at 30 degrees C in the presence of adenine exhibited increased
      sensitivity to inhibition by high salt concentrations and a lowered stability
      toward heat denaturation, indicating that the remedial effect may be the result
      of changes in the physical properties of the enzyme molecule. Temperature shift
      experiments indicate that the enzyme which is synthesized at permissive
      temperatures or under osmotic-remedial conditions is also stable in vivo under
      non-permissive conditions. This suggests that the critical period for temperature
      sensitivity, and conversely osmotic remediability, may be during protein
      synthesis or during the conformational folding of the protein.

PMID- 16094965
TI  - Effect of different conformations of galactose messenger RNA on gene expression
      and messenger half-life in vitro.
AB  - From a DNA-directed cell-free system, functional gal mRNA is obtained which
      directs the cell-free synthesis of the three galactose enzymes of Escherichia
      coli. A substantial fraction of this gal mRNA has the properties of a
      polycistronic messenger. Exposure to elevated temperatures in the presence or
      absence of magnesium ion results in pronounced changes of the capacity of this
      mRNA to give rise to the synthesis of the three enzymes. Depending on the
      conditions of the pre-treatment, the absolute amounts as well as the ratio of the
      three gene products synthesized can be changed. The different forms of gal
      messenger so obtained also exhibit different susceptibilities towards functional
      inactivation during the enzyme synthesis reaction. As the changes in template
      activity are reversible, it is concluded that the different treatments cause
      reversible transitions between different conformations of the gal mRNA.

PMID- 16094966
TI  - Genetic control of maltase formation in yeast. III. Isolation and
      characterization of temperature-sensitive mutants affecting maltase induction and
      maltose utilization.
AB  - Temperature-sensitive mutants affecting maltose utilization in the yeast
      Saccharomyces cerevisiae have been isolated. Two such mutants although failing to
      ferment maltose at the restrictive temperature, have normal induced level of
      maltase. The third mutant (UNT-37) not only failed to ferment maltose but has 5-6
      fold less induced level of maltase at the restrictive temperature than the
      parental strain. The genetic control mechanisms of maltase induction and maltose
      utilization have been discussed.

PMID- 16094967
TI  - Insensitivity of D-amino acid dehydrogenase synthesis to catabolic repression in
      dadR mutants of Salmonella typhimurium.
AB  - It has been found that synthesis of D-amino acid dehydrogenase in Salmonella
      typhimurium is stimulated by cyclic AMP and crp gene product. This indicates that
      catabolic control of the dehydrogenase resembles other bacterial systems of
      catabolic repression. We have isolated S. typhimurium mutants, dadR, which are
      resistant to L-methionine-interference with D-histidine utilization and are able
      to utilize D-tryptophan as a precursor of L-tryptophan. Mapping data indicate
      that the dadR locus is closely linked to dadA coding for the structure of D-amino
      acid dehydrogenase. The synthesis of the dehydrogenase in dadR mutants is
      completely insensitive to the repression by glucose, but remains inducible by L
      alanine. We conclude thereof that dadR mutants have changes in the promoter
      region which increase the expression of the dadA gene in the presence of glucose
      metabolism. A likely possibility that induction of the dad operon by alanine
      might be under positive control is discussed.

PMID- 16094968
TI  - The effect of three rad genes on survival, inter- and intragenic mitotic
      recombination in Saccharomyces. I. UV irradiation without photoreactivation or
      liquid-holding post-treatment.
AB  - The effect of UV irradiation on the survival, inter- and intragenic mitotic
      recombination of 3 diploid UV sensitive Saccharomyces mutants was studied and
      compared with the wild type RAD. These strains, homozygous for either the RAD,
      r1s rad 9-4, or rad 2-20 gene, have DRF values for survival of 1:1.6:3:20.6
      respectively, at LD1. Their recombination behaviour is not correlated to their
      survival characteristics. The RAD, r1s, and rad 2-20 strains showed UV induced
      mitotic inter- and intragenic recombinants; the induction in the r1s diploid is
      ca. 100 times greater for both the inter- and intragenic recombinants than in the
      RAD strain. The rad 9-4 diploid produced no UV induced mitotic recombinants
      whatsoever, and is therefore considered to be a rec- mutation.

PMID- 16094969
TI  - The influence of glutamic acid and arginine on the competence of Bacillus
      subtilis growing in a chemostat.
AB  - Using a new method to get stable steady state levels of competence in B.
      subtilis, we have obtained in our experimental conditions 0.1% competence as
      determined by the frequency of transfection with phage SPP1 DNA. The effect of
      growth rate (DT) and certain amino acids on the competence levels was also
      determined.

PMID- 16094970
TI  - In vitro synthesis of enzymes of the tryptophan operon of Escherichia coli.
AB  - In vitro synthesis of enzymes of the tryptophan (trp) operon of E. coli was
      studied in an extract prepared from E. coli, which is programmed with purified
      DNA from trp transducing phages with mutations that effect the expression of the
      trp genes in various ways. Our results show that control of transcription, i.e.
      initiation and termination, is similar in vivo and in vitro.

PMID- 16094971
TI  - Punctuation of transcription in vitro of the tryptophan operon of Escherichia
      coli. A novel type of control of transcription.
AB  - RNA transcribed in vitro from DNA of a tryptophan (trp) transducing strain of
      bacteriophage phi80 which contains the trp regulatory elements consists of a
      polycistronic messenger transcribed from the structural genes, and possibly the
      regulatory region, and a separate RNA species (called trp regRNA) which is
      transcribed from the regulatory region. This conclusion is based on hybridization
      experiments with trp RNA synthesized in vitro and the separate DNA strands of trp
      transducing strains of lambda with and without the trp regulatory elements. The
      length of trp regRNA determined by filtration on Sephadex G-200 is 110-180
      nucleotides. From the amount and the length of trp regRNA we have calculated that
      8-20 copies of trp regRNA are synthesized per copy of polycistronic trp mRNA. We
      conclude that during transcription of the trp operon RNA polymerase frequently is
      rejected at a specific site ahead of the first structural gene, trpE. The
      termination factor Rho is not involved in this process. A different protein
      fraction, which specifically stimulates the synthesis of trp enzymes in an in
      vitro protein-synthesizing system (Pouwels and Van Rotterdam, 1975), was found to
      antagonize the abortive synthesis of trp mRNA. A model is proposed for the
      control of transcription of the trp genes, which operates through a mechanism of
      punctuation of RNA synthesis at a specific site on the DNA template and anti
      termination of RNA synthesis by means of a positive control factor.

PMID- 16094972
TI  - In vitro synthesis of enzymes of the tryptophan operon of Escherichia coli.
      Evidence for positive control of transcription.
AB  - A protein fraction, called At (= anti termination) factor, has been isolated from
      extracts of E. coli and partially purified. The At factor stimulates the
      synthesis in vitro of anthranilate synthetase, an enzyme encoded by two genes of
      the tryptophan (trp) operon, but has no effect on the synthesis of T7 RNA
      polymerase and other T7- and T4 coded proteins. The At factor stimulates the
      synthesis of trp mRNA; it has no effect on the translation of trp mRNA. We
      conclude that in vitro transcription of the trp operon is positively controlled.

PMID- 16094973
TI  - Transcription of repetitive DNA in Neurospora crassa.
AB  - Repeated DNA sequences of Neurospora crassa were isolated and characterized.
      Approximately 10-12% of N. crassa DNA sequence were repeated, of which 7.3% were
      found to be transcribed in mid-log phase of mycelial growth as measured by
      DNA:RNA hybridization. It is suggested that part of repetitive DNA transcripts in
      N. crassa were mitochondrial and part were nuclear DNA. Most of the nuclear
      repeated DNAs, however, code for rRNA and tRNA in N. crassa.

PMID- 16094974
TI  - The nature of the gal3 mutation of Escherichia coli.
AB  - The gal3 mutation of the galactose operon of E. coli, first described by Morse,
      Lederberg, and Lederberg in 1956, exhibits several unique and unusual properties.
      This mutation originated spontaneously and also reverts spontaneously, but fails
      to respond to various chemical mutagens. It is extremely polar, but the polarity
      is not relieved by nonsense suppressors. The gal+ revertants are of at least two
      different kinds. One class of revertants is stable and exhibits inducible enzyme
      synthesis, whereas the other class is unstable and constitutive. The properties
      of gal3 can be explained by the assumption that this mutation was caused by the
      insertion of a DNA sequence in the operator-promoter region of the gal operon.
      This proposal was tested by the construction of a gal3 derivative of a lambdagal+
      phage and comparison of the physical properties of the two phages. Density
      gradient centrifugation studies indicated that the gal3 mutation was accompanied
      by a 0.0033 g/ml increase in the buoyant density of the phage. This increase in
      density corresponds to the addition of 1200 base pairs. This observation was
      confirmed by electron microscopy of lambdagal+/lambdagal3 heteroduplexes. A
      single-stranded addition loop, 1160 base pairs in length, was found at a fixed
      position. It was concluded that the gal3 mutation was caused by the insertion of
      a sequence similar to IS3 in length. These studies also permit an estimation of
      the physical size of the gal operon. It is found to be 3600 base pairs long,
      separated from the attlambda (B.P') site by approximately 14000 base pairs.

PMID- 16094975
TI  - Mechanism of reversion of the gal3 mutation of Escherichia coli.
AB  - The gal3 mutation is an insertion of a DNA sequence in the operator-promoter
      region of the galactose operon of E. coli. It reverts spontaneously to produce
      three kinds of gal+ revertants, which are: (i) stable and inducible, (ii) stable
      and constitutive, and (iii) unstable and constitutive. The constitutive
      revertants also show drastically reduced frequencies of transduction with lambda.
      The mechanism by which these reversions occur has remained unknown. It is
      proposed that the stable and inducible revertants arise by accurate excision of
      the insertion sequence. The unstable and constitutive revertants arise by tandem
      duplications of the gal operon in such a way that the structural genes of the
      extra copy of gal operon become connected to a different promoter. The resulting
      tandem configuration (gal3 ETK...P'E'T'K') permits constitutive expression and
      gal3 segregation (by internal recombination) simultaneously. The proposal was
      tested by comparison of the buoyant densities in CsCl of derivatives of a
      lambdagal phage carrying gal+, gal3, and the inducible and constitutive
      revertants. The densities of the inducible revertants were identical to the wild
      type, and the slight increase in density found to be associated with the gal3
      insertion was missing. It was concluded that inducible revertants arise by
      excision of the inserted sequence. In contrast, lysates of a constitutive
      revertant exhibited several anomalous properties. The lysates contained a small
      quantity of phage whose density was identical to lambdagal3, produced few gal+
      transductants (10(-3)-10(-4) of a normal HFT lysate), and the transductants were
      stable and constitutive. In turn, these abnormal transductants produced lysates
      which showed no lambdagal particles on centrifugation, and no transducing
      activity whatsoever. These anomalous properties of the constitutive revertant
      were attributed to the failure of lambda to package the DNA duplication
      efficiently. Transduction experiments with P1 (which can package more DNA than
      lambda) show that the unstable, constitutive reversions were located adjacent to
      prophage lambda. Segregation of the gal and lambda markers among the gal+
      transductants was in accordance with the pattern expected for a duplication.
      Introduction of a recA marker resulted in stabilization of the reversion without
      affecting its constitutive expression. It was concluded that the unstable,
      constitutive reversion was a tandem duplication. It is further proposed that the
      stable, constitutive class of revertants might represent inverted (gal3
      ETK...K'T'E'P') or partial tandem (gal3 ET...E'T'K') duplications of the gal
      operon.

PMID- 16094976
TI  - A constitutive mutation, phoT, of the repressible acid phosphatase synthesis with
      inability to transport inorganic phosphate in Saccharomyces cerevisiae.
AB  - Wild-type cells of Saccharomyces cerevisiae cultivated in low-Pi medium actively
      accumulate inorganic phosphate (Pi), while the same cells cultivated in high-Pi
      medium do not. A recessive constitutive mutant (phoT), for repressible acid
      phosphatase (EC 3.1.3.2) synthesis, is described. It shows severely reduced
      potency of Pi uptake, while the recessive constitutive mutants, phoR and phoU, in
      the same system show wild-type potency as.

PMID- 16094977
TI  - The effects of three rad genes on UV induced mutation rates in haploid and
      diploid Saccharomyces cells.
AB  - Effects of the rad 2-20, rad 9-4, r1s, and the corresponding wild type RAD
      alleles in haploid and homozygous diploid Saccharomyces strains on UV induced
      mutation rates from adenine, lysine and histidine dependence to independence are
      reported. The UV induced mutation rates were similar for the RAD, r1s, and rad 9
      4 haploids, whereas the rad 2-20 mutation causes a marked increase in the UV
      induced mutation rates. The diploid rad 2-20 strain also exhibits a marked
      increase in the UV induced mutation rates, whereas the rad 9-4 diploid has
      reduced mutation rates when compared to the wildtype. The UV induced mutation
      rates of haploid and diploid RAD strains are almost identical. For the rad 2-20
      and rad 9-4 diploids, however, these rates are smaller than in the corresponding
      haploid strains. Differential effects of the rad genes on the ratio of locus to
      suppressor mutations were found. The implications of these findings on possible
      repair processes in yeasts are discussed.

PMID- 16094978
TI  - Ultraviolet light-induced mutation in UV-resistant, thermosensitive derivatives
      of lexA-strains of Escherichia coli K-12.
AB  - It was shown previously that a major class of UV-resistant derivatives of lexA-
      strains of E. coli K-12 is defective in cell division at 42.5 degrees. The
      thermosensitive mutations, judging by genetic mapping and complementation tests,
      are believed to be intragenic suppressor mutations that lower the activity of the
      diffusible product that results in the LexA- phenotype (Mount et al., 1973).
      Several thermosensitive derivatives have been characterized in regard to their
      susceptibility to mutation induction by UV at the permissive growth temperature
      (30 degrees). Although the strains tested are approximately as resistant to UV as
      lexA+ strains, they showed a level of mutation induction that was considerably
      lower. By means of genetic complementation tests it was demonstrated that the low
      levels of UV mutagenesis in lexA- strains and their thermosensitive derivatives
      result from the synthesis of a diffusible product. One possible interpretation of
      these results is that a diffusible product in lexA- strains prevents the
      induction of error-prone repair. Altering the activity of this product by tsl
      mutations can lead to increased, but not normal, levels of error-prone repair.

PMID- 16094979
TI  - Deletions in bacteriophage P2. Circularity of the genetic map and its orientation
      relative to the DNA denaturation map.
AB  - Several types of viable chromosomal deletions of bacteriophage P2 were isolated.
      One type gives the immunity insensitive phenotype and may extend to the genes for
      the immunity repressor (C) and for integrative recombination (int). Two other
      types delete genes (old and fun) known to be active in the lysogenic state. For
      such deletion mutants the relationship between particle density and DNA length
      was established. The deletions were located in respect to previously mapped genes
      and the results were compared with electron microscopical studies (by Inman and
      collaborators) of the P2 chromosome. It is concluded that the best representation
      of the genetic map of P2 is circular. The cohesive ends of the linear P2 DNA
      molecule are most likely formed between genes old and Q. Except for the
      neighborhood of gene old, the previously published, linear genetic map of P2
      (Lindahl) is colinear with the melting map of the P2 chromosome (Inman).
      Preliminary evidence for some specific recombination event often accompanying
      integrative recombination between phage chromosomes is presented.

PMID- 16094980
TI  - Physical mapping of bacteriophage P2 mutations and their relation to the genetic
      map.
AB  - Three new deletion mutants and an insertion mutant of E. coli bacteriophage P2,
      del2, vir79, del4 and sig5, were mapped by the electron microscope heteroduplex
      method. The deletions were found to cover 45.5-51.6%, 75.6-76.7% and 92.3-99.3%
      respectively of P2 DNA while sig5 represented a 3.7% insertion at 78.6% from the
      left end. The region covering 75.9-76.7% of P2 DNA is also deleted in the two
      previously characterized immunity insensitive variants of P2, vir22 and Hy dis.
      This region may identify the portion of the genome responsible for immunity. The
      physical and genetic maps of P2 were previously found to be colinear with respect
      to the two mutations vir22 and vir37. This relationship is confirmed by the
      position of del2.

PMID- 16094981
TI  - DNA nucleotide sequence homologies between some zoosporic fungi.
AB  - Representative species from the monoflagellate Blastocladiales and the
      biflagellate Saprolegniales were studied for their DNA base composition,
      heterogeneity, nucleotide sequence homology and divergence. Intergeneric,
      intrageneric and interstrain DNAs of Blastocladiales were heterogenous. The G+C
      values for their main component (average 64 percent) and two minor ones (average
      52 and 44 percent) were found to be significantly higher than the corresponding
      values from the biflagellate Saprolegnia ferax (55, 46 and 36 percent
      respectively). In Allomyces species, the two hybrid, male and female strains were
      found to have closer homology with their parental types than these last between
      themselves. Among Blastocladiales, interspecific similarities between the
      epigynous A. macrogynus and the hypogynous A. arbuscula were higher (average 75
      percent) than intergeneric similarities between Allomyces and Blastocladiella
      (average 58 percent). The biflagellate S. ferax was found to be distantly related
      to the uniflagellate Allomyces (average 48 percent similarity). The nucleotide
      sequence divergences obtained from thermal elution data correlated the
      hybridization values.

PMID- 16094982
TI  - Bacterial mutants able to partly suppress the effect of N mutations in
      bacteriophage lambda.
AB  - A method is described whereby bacterial mutants (sun) may be selected which are
      able to specifically suppress mutations in the N gene of bacteriophage lambda.
      The sun mutations seem to be allelic to suA mutations, which suppress the
      polarity of nonsense codons, since suA mutants have all of the properties of sun
      mutants and both are genetically linked to the ilv gene. In the light of these
      experiments and recent data by others, models originally suggested to explain
      polarity in bacterial operons, are discussed with regard to their possible
      relevance to the mechanism of N action.

PMID- 16094983
TI  - The nature of the product of the cys B gene of Escherichia coli.
AB  - Amber and temperature-sensitive mutations have been isolated in the cys B gene of
      Escherichia coli. Their existence suggests that the gene codes for a protein.

PMID- 16094984
TI  - [Fluorescence of tetracycline antibiotics in human dental pulp].

PMID- 16094985
TI  - [The shape, dimensions and position of the upper frontal teeth in men and women.
      Analysis of 700 cases].

PMID- 16094986
TI  - [The response of muscular tissue to EDTA].

PMID- 16094987
TI  - [Simple method of examination of the pH of saliva].

PMID- 16094988
TI  - [Jaw traumatology in Karvina].

PMID- 16094989
TI  - [The diagnosis and treatment of processus styloidei elongati].

PMID- 16094990
TI  - [Problems of general anesthesia in out-patients stomatology].

PMID- 16094991
TI  - [Lymphosarcoma of the parotid gland in Sjogren syndrom].

PMID- 16094992
TI  - [Closure of palatal defect by tubular flap].

PMID- 16094993
TI  - [Symtoms of primary hyperparathyrosis in jaw bones].

PMID- 16094994
TI  - [Notes on the technique of general anesthesia for the purposes of stomatologic
      surgery. Experience with halothane administered by modified vaporizer according
      to Jadrny].

PMID- 16094995
TI  - [Functional concept of contemporary orthodontics in France].

PMID- 16094996
TI  - Plasmid ColE1 DNA replication in Escherichia coli strains temperature-sensitive
      for DNA replication.
AB  - Mutants of the dnaA, dnaC, dnaD, polC, dnaF and dnaG gene loci were tested for
      their capacity for colicinogenic plasmid E1 (ColE1) replication at a non
      permissive temperature. It was found that ColE1 replication was independent of
      the dnaA gene function and dependent on dnaC, D, F and G. ColE1 replication in
      the polC mutant E486 continued for several hours but at a greatly reduced rate.
      No effect was found of the dnaG mutation on thymine-deprivation-induced "priming"
      of ColE1 replication at the non-permissive temperature. The mutants also were
      tested for aberrant replication intermediates of plasmid DNA as well as a
      temperature sensitive supercoiled DNA-protein relaxation complex. RNA-containing
      supercoils were found to accumulate in a poIC mutant also blocked for protein
      synthesis.

PMID- 16094997
TI  - E. coli K12 inf: a mutant deficient in prophage lambda induction and cell
      filamentation.
AB  - The bacterial mutant inf-3 (lambda) is not inducible and does not form filaments
      following thymine starvation. Lysogenic induction is neither produced by
      ultraviolet light (UV) nor promoted by tif-1. This phenotype is due to a mutation
      infA3 located between 60 and 73 min on the E. coli K12 map. The inf mutant is
      resistant to X-ray and UV irradiation, in contrast to all other known non
      inducible bacterial mutants. It is Rec+ and able to perform host cell
      reactivation as well as UV-reactivation of phage lambda. After exposure to UV
      light, its DNA is degraded more than that of the parent and the resumption of DNA
      synthesis is delayed by 30 min; nevertheless, the cell survival is analogous to
      that of the parent. The inf mutant is also resistant to thymine starvation, for
      at least 3 hours. Wild type phage lambda forms clear plaques on a lawn of non
      lysogenic inf bacteria; a corresponding low level of lysogenization is found. The
      capacity of inf bacteria to reproduce phages lambda, T4 or T6 is impaired. No
      gross defect in DNA transcription has been detected. Nevertheless, this mutant
      might have a slight alteration in the transcription process or in any other
      process involved in gene expression. This alteration might affect the regulation
      of DNA replication and cell division as well as prophage lambda induction.

PMID- 16094998
TI  - Influence of edeine on intergenic and interallelic recombination in Neurospora
      crassa.
AB  - The effect of edeine and the mutation edr-2 to edeine resistance on genetic
      recombination in Neurospora crassa was investigated. For this purpose crosses
      between pairs of edeine sensitive and edeine resistant strains respectively were
      set up without or in the presence of the drug (0-750 microg/ml). The genetic
      markers ylo-1, ad-1, pan-2 (B3 and B5) and tryp-2, all on linkage group VI, were
      used for scoring recombinants. These were ad+, tryp+ (intergenic recombination)
      and pan+ (interallelic recombination). Frequencies of about 6-7% for intergenic
      and of about 0.4% for interallelic recombination were found in crosses between
      eds strains and ed(r) strains respectively, if edeine was absent. However,
      crosses in the presence of edeine gave higher frequencies of both intergenic and
      interallelic recombination (about 12% intergenic and 1% interallelic with 180 to
      200 microg ed/ml). The pan+ prototrophs (interallelic recombinants) obtained in
      the different crosses were tested for distribution of outside markers. The data
      thus obtained revealed that under the effect of both the mutation to edeine
      resistance and edeine itself the relative number of noncrossover (gene
      conversion) recombinants decreases in favour of crossover recombinants, and the
      relative number of double crossover recombinants (events outside the pan locus)
      decreases in favour of single crossover recombinants. It is concluded that a)
      edeine and the mutation ed(r)-2 to edeine resistance affect recombination via
      related pathways, and b) noncrossover and crossover recombinants are caused by
      different molecular mechanisms, in agreement with the work of other authors.

PMID- 16094999
TI  - Unaltered stability of newly synthesized RNA in strains of Escherichia coli
      missing a ribonuclease specific for double-stranded RNA.
AB  - Pairs of very closely related Escherichia coli strains were prepared, one having
      the wild-type allele for ribonuclease III, an enzyme which specifically degrades
      double-stranded RNA, and the other having a mutant RNase III allele. Growth and
      phage plating efficiency were compared in these strains. The RNase III+ strains
      grow better than the RNase III- strains and plate T7 and lambda phage better, but
      T4 plates with the same efficiency on both strains. On the other hand, the half
      lives of newly synthesized RNA as well as of functional beta-galactosidase mRNA
      are similar in both kind of strains. These two parameters, however, are
      significantly longer in both strains as compared to the original strain from
      which they were derived. Also, no difference in the differential induction of
      beta-galactosidase was observed between such strains. Thus, we have to conclude
      that either ribonuclease III does not play a significant role in the functioning
      and stability of newly synthesized mRNA, or that enough enzymatic activity was
      left, residual RNase III or some other enzyme to deal with double-stranded
      regions in the message.

PMID- 16095000
TI  - Genetical aspects of [URE3], a non-mitochondrial, cytoplasmically inherited
      mutation in yeast.
AB  - [URE3], a non-mitochondrial non-mendelian mutation which modifies drastically
      yeast nitrogen metabolism has been genetically studied. Cytoduction experiments
      show definitely that the inheritance of the determinant is not linked to the
      nucleus. The maintenance of the [URE3] determinant seems controlled by the
      product of a conventional nuclear gene (ure2) which is itself involved in
      nitrogen metabolism. The (ure2) mutation alone gives the same phenotype as [URE3]
      but it is impossible to obtain a stable recombinant containing simultaneously the
      (ure2) mutation and the [URE3] determinant. Application of the Newcombe
      respreading experiment demonstrates that the [URE3] mutational event occurs
      before the selection procedure and is therefore not strictly adaptative.
      Nevertheless, the nature of the selection medium changes considerably the
      frequency of the [URE3] mutants recovered.

PMID- 16095001
TI  - Identification of the structural gene of the PEP-phosphotransferase enzyme I in
      Bacillus subtilis Marburg.
AB  - A thermosensitive mutation pt8I1 in the gene coding for the Enzyme I of the PEP
      phosphotransferase system pathway has been isolated. The mutant enzyme was shown
      to be sensitive to high temperature, but this effect is dependent on the ionic
      strength. The ptsI1 mutation was shown to belong to the previously described ctr
      locus. Following Lin (1970) it is proposed to retain the symbole ptsI for this
      locus.

PMID- 16095002
TI  - Regulation of gene expression in Salmonella phage P22. II. Regulation of
      expression of late functions.
AB  - Transactivation experiments were performed involving the genetically related
      Salmonella phages P22, L and Px1 in order to find out if more than one positively
      acting regulatory product is engaged in the expression of vegetative gene
      functions of each of these phages. The results obtained with Px1- and L-lysogenic
      cells superinfected with P22 suggest the following conclusions: 1. The expression
      of the early genes 12 and 23 and of the late gene 19 (lysozyme synthesis) is
      positively regulated by two different regulatory products, since P22
      transactivates in prophage Px1 both early and late genes (Prell, 1973), in
      prophage L only late genes. 2. The transactivation by P22 of the lysozyme gene of
      prophage L takes place in the presence of L repressor. This conclusion is
      suggested, since the superinfecting P22 does not derepress early gene expression
      (see 1.), and is confirmed by demonstration of replication inhibition for L phage
      in L lysogenic cells doubly superinfected with L and P22 phages (Thomas-Bertani
      experiment). 3. The late gene regulatory protein seems to be synthesized by gene
      23, as transactivation experiments with both L- and Px1 prophages suggest. 4. The
      expression of gene 23 itself is turned on by an early regulatory product. The
      gene which codes for it is still unidentified. However its product seems to by
      highly specific, since it is active on Px1- but not on L-prophage.

PMID- 16095003
TI  - Diagnostic and prognostic significance of autoantibodies in early rheumatoid
      arthritis.
AB  - A positive rheumatoid factor (RF) test has been included as one of the criteria
      for the diagnosis of rheumatoid arthritis (RA) according to the 1987
      classification criteria of the American College of Rheumatology (ACR). During the
      past 20-30 years many different autoantibodies have been described in patients
      with RA. The presence of some of the autoantibodies in RA directed against
      various autoantigens, such as anti-neutrophil cytoplasmic antibodies, anti
      nuclear antibodies, antibodies against interleukin-1 (IL-1), anti-cardiolipin
      antibodies, and antibodies against oxidized low density lipoprotein, is not
      specific for RA and these are not discussed here. This review summarizes the most
      relevant autoantibodies, and discusses their sensitivity, specificity, and
      possible diagnostic and prognostic significance in early RA. The antibodies are
      presented with the two clinically most relevant antibody tests first, followed by
      others in alphabetic order.

PMID- 16095004
TI  - Therapy of ankylosing spondylitis--a review. Part I: Conventional medical
      treatment and surgical therapy.
AB  - The main outcome parameters in AS and other SpA are pain, disease activity,
      function, spinal mobility, and structural progression. There are several
      treatment options, which differ, depending on the localization and severity of
      the manifestation and the degree of structural changes already present. There is
      a basic role for physiotherapy to improve and maintain spinal mobility and
      function and prevent handicap. The basis for drug therapy in AS is NSAIDs, which
      may also have an influence on structural progression. DMARDs are mainly used in
      cases with peripheral arthritis. Corticosteroids have a clear role for intra
      articular therapy, while the role for systemic use is, in contrast to RA, mainly
      reserved for subgroups. It is largely unclear whether long-term spinal
      progression can be prevented by conventional drug therapy. Treatment with
      biologics such as anti-TNF-alpha therapy is discussed in Part 2 of this review.
      To be published in the next issue of the Scandinavian Journal of Rheumatology.
      Surgical treatment of the spine is indicated in cases of severe instability pain,
      in cases of deformity endangering the patient in daily life by the limited range
      of vision, and in patients with neurological deficiency. AS-specific problems are
      spinal fractures and atlantoaxial instability, which need careful management
      including surgery. Joint replacement therapy is established and beneficial for AS
      disturbed joints of the hip and knee.

PMID- 16095005
TI  - IL-6 promoter polymorphism in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which
      cytokines play an important role. The aim of the present study was to examine the
      interleukin-6 (IL-6) -174 promoter polymorphism in patients with RA and its
      association with disease susceptibility and activity. METHODS: The study included
      98 patients with RA diagnosed according to the criteria of the American College
      of Rheumatology. Polymerase chain reaction (PCR) amplification was used for
      analysis of the polymorphism at position -174 in the promoter of the IL-6 gene.
      RESULTS: The distribution of IL-6 genotypes in RA patients did not differ from
      that in control subjects. Nevertheless, in patients with a GG genotype the active
      form of RA was more frequently diagnosed compared with homozygous CC and GC
      patients. Moreover, in carriers of two G alleles the parameters of disease
      activity score (DAS28), erythrocyte sedimentation rate (ESR), number of swollen
      and tender joints] were significantly increased. CONCLUSION: We suggest that the
      IL-6 promoter polymorphism may be a genetic risk factor for RA activity.

PMID- 16095007
TI  - Anti-nucleosome antibodies in the diagnosis of systemic lupus erythematosus.
AB  - OBJECTIVE: To study the prevalence and diagnostic significance of antibodies
      against nucleosomes in patients with systemic lupus erythematosus (SLE) as
      compared to five anti-nuclear antibody (ANA) assays. METHODS: The study included
      305 patients with SLE, 125 patients with other autoimmune rheumatic diseases, and
      415 healthy controls. Anti-nucleosome antibodies were measured by an enzyme
      linked immunosorbent assay (ELISA) and ANA by immunofluorescence (IF) using Hep-2
      cells. Anti-double-stranded DNA (anti-dsDNA) antibodies were measured by three
      commercial ELISAs and by IF using Crithidia luciliae as antigen. RESULTS:
      Compared to three ELISAs for anti-dsDNA, the anti-nucleosome assay was less
      sensitive (30% vs. 29-69%) but equally specific (90% vs. 77-95%) for SLE. The
      most sensitive test was ANA (76%), and the least sensitive was Crithidia (13%).
      The correlations between the different assays were good (p < 0.001 for all
      comparisons). CONCLUSION: The anti-nucleosome antibody assay does not offer
      additional information compared to conventionally used anti-dsDNA tests in the
      differential diagnosis of SLE.

PMID- 16095006
TI  - Extended haplotype analysis reveals an association of TNF polymorphisms with
      susceptibility to systemic lupus erythematosus beyond HLA-DR3.
AB  - OBJECTIVE: To study the relative contribution of tumour necrosis factor (TNF) and
      HLA-DRB1 polymorphisms to the genetic susceptibility to systemic lupus
      erythematosus (SLE) via an extended haplotype analysis. METHODS: We performed an
      association study in 205 unrelated German Caucasian patients with SLE fulfilling
      the 1997 revised American College of Rheumatology (ACR) criteria. Healthy age-,
      ethnically- and sex-matched individuals (n = 157) served as controls. HLA-DRB1
      typing was performed by a sequence-specific oligonucleotide hybridisation assay.
      Two TNF single nucleotide polymorphisms (SNPs) and two multiallelic
      microsatellites were analysed by mutagenically separated polymerase chain
      reaction (PCR) or fragment length analysis, respectively. Extended haplotypes
      were reconstructed with the PHASE software. RESULTS: Alleles for all polymorphic
      loci studied and the most frequent haplotypes showed a significantly different
      distribution between SLE patients and controls. The alleles HLA-DR2, DR3, TNFd1,
      TNF2, TNFB*1, and TNFa2, designated as risk alleles, and the extended haplotypes
      DR3-TNFd1-TNF2-TNFB*1-TNFa2 and DR2-TNFd3-TNF1-TNFB*2-TNFa11 prevailed in SLE
      patients. TNF risk alleles were strongly positively linked with HLA-DR3 and
      negatively linked with HLA-DR2. Thus, in HLA-DR3 haplotypes individual effects of
      TNF polymorphisms could not be resolved. By contrast, HLA-DR2 showed an
      association with SLE independently of TNF risk alleles, while the risk increased
      further when they were present. In haplotypes lacking HLA-DR2 and DR3, the
      alleles TNFdl and TNF2 contributed independently to SLE susceptibility.
      CONCLUSION: Extended haplotype analysis revealed HLA-DR3 independent associations
      of TNF polymorphisms with susceptibility to SLE. Haplotypes that have been shown
      to be associated with different TNF-alpha production capacity may prevail in
      different disease subgroups.

PMID- 16095008
TI  - A longitudinal study of calprotectin in patients with polymyalgia rheumatica or
      temporal arteritis: relation to disease activity.
AB  - OBJECTIVE: Calprotectin is a granulocyte and monocyte cytosolic protein that is
      released during activation of these cells. The plasma level of calprotectin is
      raised in various inflammatory conditions and correlates with disease activity in
      a wide range of rheumatic diseases. We wanted to investigate whether calprotectin
      may be useful as a measure of disease activity in polymyalgia rheumatica (PMR)
      and temporal arteritis (TA). METHODS: Forty-seven patients with PMR and/or TA
      were followed up to 3 years in a prospective longitudinal design. Plasma
      calprotectin was correlated with acute phase parameters, erythrocyte
      sedimentation rate (ESR), and peroral steroid usage before start of treatment and
      at four subsequent time intervals. RESULTS: Thirty-three patients had PMR, 10 had
      TA, and four had both diagnoses. Calprotectin was highly correlated with the
      acute phase parameters and ESR during the study period. Calprotectin was
      significantly decreased after start of treatment with oral prednisolone, and
      correlated with the daily dosage of prednisolone (r = 0.36, p < 0.01).
      CONCLUSION: Calprotectin plasma levels were significantly associated with acute
      phase parameters, ESR, and prednisolone usage in PMR and TA, indicating that
      calprotectin may be a good measure of disease activity in these conditions.

PMID- 16095009
TI  - Enhanced production of macrophage inhibitory protein-1alpha in patients with
      Behcet's disease.
AB  - OBJECTIVE: Macrophage inhibitory protein-1alpha (MIP-1alpha), a C-C chemokine,
      stimulates the activation and migration of leukocytes. We investigated the
      expression of MIP-1alpha in patients with Behcet's disease (BD) and evaluated the
      association of the MIP-1alpha levels with disease activity of BD. METHODS: Serum
      samples were obtained from 67 BD patients and 30 healthy controls.
      Simultaneously, whole blood cells were isolated from BD patients (n = 25) and
      healthy controls (n = 11) and cultured in the absence or presence of
      lipopolysaccharide (LPS), phytohaemagglutinin (PHA), and phorbol 12-myristate 13
      acetate (PMA) plus ionomycin. The concentrations of MIP-1alpha, interleukin-8 (IL
      8), regulated on activation, normally T cell expressed and secreted (RANTES), and
      monocyte chemoattractant protein-1 (MCP-1) were measured in the sera and culture
      supernatants by enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum
      levels of MIP-1alpha were higher in BD patients than in healthy controls. When
      whole blood cells were stimulated with LPS or PMA plus ionomycin, but not PHA, BD
      patients had higher levels of MIP-1alpha in the culture supernatants compared to
      healthy controls. In sera and culture supernatants of whole blood cells, MIP
      1alpha levels correlated well with those of RANTES, MCP-1, and IL-8 in BD
      patients. Moreover, patients with active disease had significantly higher levels
      of serum MIP-1alpha levels compared with those with inactive disease. CONCLUSION:
      MIP-1alpha levels were elevated in patients with BD, and correlated well with IL
      8, RANTES, and MCP-1 levels. These results suggest that the increased MIP-1alpha
      levels in serum of BD patients may lead to activation and migration of
      leukocytes, playing a role, like other chemokines, in the pathogenesis of BD.

PMID- 16095010
TI  - Treatment of intravenous immunoglobulin-resistant Kawasaki disease with
      methotrexate.
AB  - OBJECTIVE: To evaluate the effect of low-dose oral methotrexate (MTX) as
      treatment for patients with Kawasaki disease (KD) resistant to intravenous
      immunoglobulin (IVIG). METHODS: The subjects were four patients with KD, aged 8
      months to 8 years old, who showed persistent disease after treatment with high
      dose IVIG (2 g/kg) and aspirin (100 mg/kg). These patients were re-treated with
      IVIG and were also treated with IV dexamethasone (0.3 mg/kg). IV dexamethasone
      induced defervescence in three patients, but fever recurred upon discontinuing
      the steroid. One patient showed no response to either IVIG or dexamethasone. All
      patients were subsequently treated weekly with low-dose oral MTX [10 mg/body
      surface area (BSA)]. RESULTS: MTX treatment resulted in rapid defervescence,
      improvement in clinical symptoms, and normalization of acute-phase reactants in
      all patients. There was no progression of coronary artery dilatation and MTX was
      discontinued with no recurrence of fever. No adverse effects of MTX were
      observed. CONCLUSION: Low-dose oral MTX is an effective treatment for refractory
      KD.

PMID- 16095011
TI  - The prevalence of fibromyalgia in women aged 20-64 in Turkey.
AB  - OBJECTIVE: The objectives of this study were to determine the prevalence of
      fibromyalgia syndrome (FMS) in women aged 20-64 in the city of Trabzon, Turkey,
      and to evaluate associated demographic variables. METHODS: A minimum of 1825
      subjects eligible for the study was calculated, and 2000 subjects were eventually
      planned for inclusion. Of these, 1930 subjects participated in the screening
      phase (a participation rate of 96.5%). The screening protocol included several
      interview items that have been defined as components of FMS. Subjects were also
      asked questions concerning demographics. Individuals with positive screening
      results were invited to be examined by a specialist in physical medicine and
      rehabilitation in order to confirm or exclude FMS using the 1990 American College
      of Rheumatology (ACR) classification criteria. RESULTS: Seventy of the 1930 women
      were diagnosed with FMS. The prevalence of fibromyalgia was 3.6% (95% CI 2.8
      4.4). The prevalence was highest in the 50-59 age group (10.1%, 95% CI 8.8-11.4),
      in the uneducated (10.7%, 95% CI 9.3-12.1), in the widowed (8.8%, 95% CI 7.5
      10.1), and in subjects with an annual household income of < USD 2000 (7.3%, 95%
      CI 6.1-8.5). CONCLUSION: This cross-sectional study is the first report of the
      prevalence of FMS in Turkey. These data will assist decision-making in the health
      system.

PMID- 16095012
TI  - Severe ankylosing spondylitis and diffuse systemic sclerosis: case report of a
      genetic trap.
AB  - A rare association of ankylosing spondylitis (AS) and systemic sclerosis (SSc) is
      reported in a Brazilian Mestizo patient presenting a human leucocyte antigen
      (HLA) genotype that included HLA SSc-susceptibility genes previously reported in
      different ethnic groups and HLA-B27 associated with AS. The underlying genetic
      background supporting the full expression of both SSc- and AS-susceptibility
      alleles and the pertinent literature are discussed.

PMID- 16095013
TI  - Exacerbation of Whipple's disease associated with infliximab treatment.
AB  - A 34-year-old man with chronic inflammatory joint disease and recurrent fever
      over 6 years was diagnosed as having Still's disease. Treatment with
      corticosteroids and azathioprine was ineffective. Therefore, infliximab/
      methotrexate was started. The patient subsequently developed a wasting disease
      with rapid weight loss, erythema nodosum, diarrhoea, progressive lymph node
      enlargement, and a sigmoido-vesical fistula. Histological analysis of several
      enlarged lymph nodes, the margins of the fistula, and the small bowel established
      the diagnosis of Whipple's disease (WD). The presence of Tropheryma whipplei (Tw)
      DNA in the tissues was confirmed by polymerase chain reaction (PCR). Careful re
      evaluation of biopsies taken from the ileum and the liver 2 years earlier, which
      at that time was not judged to be diagnostic for WD, retrospectively showed
      subtle histological signs of WD and were positive for Tw DNA. In summary,
      infliximab treatment seems to increase the risk of exacerbation of WD. WD should
      be carefully ruled out prior to application of tumour necrosis factor-alpha (TNF
      alpha) blockade.

PMID- 16095014
TI  - Muscular amyloidoma presenting as inguinal masses in multiple myeloma.
AB  - We report a case with protruding inguinal masses for 6 months, in whom muscular
      amyloidoma was not suspected before muscle biopsy. On pelvic magnetic resonance
      imaging (MRI), round masses showing peripheral rim enhancement with gadolinium
      were observed in iliopsoas and iliacus muscles of both inguinal areas. The same
      lesions were also observed in gluteus muscles. The biopsy showed Congo red
      positive materials in a dense fibrous background. Serum and urine electrophoresis
      showed Bence Jones protein, lambda type. In bone marrow section, myeloma cells
      were found. Peripheral blood stem cell transplantation (PBSCT) following four
      cycles of VAD (vincristine, adriamycin, dexamethasone) chemotherapy was performed
      and the result was satisfactory. Amyloidoma lesions decreased in size and number
      on the following MRI.

PMID- 16095015
TI  - Severe hypertriglyceridaemia in idiopathic (non-HCV-related) mixed
      cryoglobulinaemia.
AB  - We describe a 28-year-old male patient in whom the development of idiopathic
      mixed cryoglobulinaemia (MC) with typical clinical manifestations such as
      polyarthralgia, weakness, purpura, and Raynaud's phenomenon was associated with a
      remarkable increase in serum triglycerides (TG). Prednisone administration was
      effective in classical cryoglobulinaemia symptoms and also in dyslipidaemia.
      Infective, autoimmune, and haematological disorders are often related to
      cryoglobulinaemia and it has been analysed that some of them also show an
      increase in TG.

PMID- 16095016
TI  - Radiological and magnetic resonance imaging findings of the sacroiliac joints of
      HLA B27 antigen negative patients with chronic low back pain.

PMID- 16095017
TI  - Neck pain is a major clinical problem in ankylosing spondylitis, and impacts on
      driving and safety.

PMID- 16095018
TI  - Serum activity of endothelin-converting enzyme correlates negatively with vital
      capacity in systemic sclerosis.

PMID- 16095019
TI  - [Enhancing awareness of the modalities in the management of chronic inflammatory
      diseases].
AB  - From an epidemiologic point of view, the incidence of rheumatoid arthritis in the
      French regions we studied appears relatively stable and about the same as the
      prevalence of rheumatoid spondylosis. The incidence of Crohn's disease, among the
      chronic inflammatory bowel diseases, is currently increasing. Treatment for
      rheumatoid arthritis, other than symptomatic and maintenance treatments, now
      includes various specific forms of "biotherapy". Their development was made
      possible through the decoding of the pathophysiological mechanisms of
      inflammation and joint destruction, basically involving pro-inflammatory
      cytokines. Currently, it appears that these treatments should be limited to
      severe or active progressive rheumatoid arthritis that is resistant to
      maintenance therapy. For rheumatoid spondylosis, the prescription of anti-TNF
      alpha agents requires early diagnosis and prognostic assessment of the disease,
      together with the implementation of an individualized therapeutic strategy for
      the global multidisciplinary management of each patient. The introduction of
      immunosuppressors and anti-TNF alpha agents for chronic inflammatory bowel
      diseases constitutes a major advance in the management of their severe forms, but
      nevertheless raises the issues of whether their use should be systematic or
      depend on the severity of the disease. They also require the training of
      practitioners in their use and monitoring. Patients' groups have requested more
      collegial decision-making, decompartmentalization of practices, widespread
      development of health care networks, the development of clinical trials and
      improved communication. The regional disparities in patient management stem from
      epidemiologic variations in the demand for care and from social and demographic
      differences in the populations. They also depend on the overall health-care
      supply. Health networks can be defined as structures of coordination and non
      mandatory, non-hierarchical services to patients that help to improve care and/or
      prevention by the appropriate involvement of various healthcare professionals.
      Regional particularities are observed, as is shown by the studies conducted in
      Brittany, the Loire Valley and Nord Pas-de Calais. The questions regarding the
      networks do not concern their effectiveness in the management of chronic
      inflammatory diseases, but their structure, day-to-day operations, and financing.

PMID- 16095020
TI  - Absent or reversed end-diastolic flow in the umbilical artery: outcome at a
      community hospital.
AB  - OBJECTIVE: To describe the peripartum outcome and risk factors for neonatal death
      among pregnancies complicated with umbilical arterial absent end diastolic or
      reverse flow (AREDF UA), in a community hospital. STUDY DESIGN: The inclusion
      criteria of this retrospective analysis were: AREDF UA detected and managed at a
      community hospital. RESULTS: During the 46 months, 50 cases of AREDF UA were
      detected and the pregnancies were complicated by hypertensive disease in 52%,
      twins in 26%, and diabetes mellitus in 14%. Excluding four (8%) stillbirths of
      non-anomalous fetuses, nine newborns died and the significant differences between
      those who died and lived (n = 36) were: oligohydramnios (odds ratio [OR] 34.00,
      95% confidence intervals [CI] 4.65, 248.50), non-immune hydrops (OR 24.33, 95% CI
      1.01, 560.60) and respiratory distress syndrome (OR 7.00, 95% CI 1.27, 38.59).
      CONCLUSIONS: The risk factors for neonatal mortality with AREDF UA are
      oligohydramnios, non-immune hydrops, or respiratory distress syndrome.

PMID- 16095021
TI  - Clinical problem-solving. Dried up or washed out?

PMID- 16095023
TI  - Fence or ambulance?

PMID- 16095022
TI  - Medicare health support (chronic care model).

PMID- 16095024
TI  - The first step UM medical school to increase class size by 5 slots this fall.

PMID- 16095026
TI  - Dr. J. Edward Hill keynote speaker for 2005Health Care Ethics Symposium.

PMID- 16095025
TI  - An interview with 2005-06 MSMA president Helen R. Turner, MD, PhD. Interview by
      Karen A. Evers.

PMID- 16095027
TI  - Nasofacial zygomycosis: a case report of conidiobolus coronatus in a Hispanic
      immigrant in South Carolina.

PMID- 16095028
TI  - HER-2/neu amplified breast cancers in South Carolina.

PMID- 16095029
TI  - SC AHEC family practice residency program graduates: where are they, who do they
      serve, and what services do they provide?
AB  - The findings of this study of family practice program graduates are consistent
      with the mission of SC AHEC "to educate and retain primary health care
      providers." The graduates of these programs are providing a variety of medical
      services to a diverse patient population in South Carolina and surrounding
      states.

PMID- 16095030
TI  - Pediatric extracorporeal membrane oxygenation (ECMO): a review of the first ten
      years of experience at the Medical University of South Carolina.
AB  - ECMO can be life saving in pulmonary emergencies unresponsive to conventional ICU
      support. ECMO technology and expertise has increased immensely over the last
      decade. Our experience, and others, has demonstrated that the earlier the
      referral to an ECMO center, the better chance of survival these patients will
      have. Our survival results exceed the national average and we have used this
      therapy in a wide variety of disease processes. Long-term sequelae in survivors
      are infrequent, as most patients return to normal pulmonary function.

PMID- 16095031
TI  - Advancing medical professionalism. VI. Summing up.

PMID- 16095032
TI  - Vernon B. Moore, M.D.

PMID- 16095033
TI  - Developmental renal pathology: its past, present, and future.
AB  - Congenital anomalies of the kidney and urinary tract are responsible for
      approximately 40% of cases of childhood end-stage renal failure in the United
      States. This article describes the spectrum of developmental renal lesions in
      children (including renal agenesis, dysplasias, hereditary hydronephrosis,
      autosomal recessive and dominant polycystic kidneys, vesicoureteral reflux,
      diabetic embryopathy, some teratogenic drugs affecting renal development, and
      syndromes associated with renal dysplasias). The article quotes some historic
      references that established the foundation for further studies; reviews the
      embryology, pathology, postnatal renal development, and its possible consequences
      of renal function; as well as recent advances in fetal ultrasonography and
      molecular biology with some novel treatment and diagnostic modalities. Finally,
      an attempt is made to predict several future avenues in pharmacogenetics that are
      being built currently and that will allow a better prognosis for many children
      with congenital renal conditions.

PMID- 16095034
TI  - Chronic hepatitis C in Israeli children.
AB  - Natural history, epidemiology, and histopathological features of chronic hepatis
      C (CHC) are well established in adults. Data on histopathological findings of CHC
      in children are still limited and controversial. We aimed to evaluate the
      histopathological features of CHC in children in Israel. We reviewed,
      retrospectively, 20 liver specimens from 20 children with CHC for inflammation
      and fibrosis, hepatocyte necrosis, fatty changes, cholestasis, bile duct damage,
      sinusoidal lymphocytosis, and glycogen storage. The most common histological
      feature was portal inflammation (95%) and lobular inflammation (70%). Sinusoidal
      lymphocytosis was present in 85% and glycogen storage vacuoles in 40%. Most of
      the children (80%) had no fibrosis, 15% had mild fibrosis and 5% moderate
      fibrosis. Advanced fibrosis or cirrhosis was not found. No correlation was found
      between the age at biopsy and any of the histological parameters. Our study shows
      that children with CHC have a different phenotype of liver disease with slowly
      progressive natural history irrespective of duration of the disease.

PMID- 16095035
TI  - Tuberous sclerosis: immunohistochemistry expression of tuberin and hamartin in a
      31-week gestational fetus.
AB  - Tuberous sclerosis complex (TSC) is a common autosomal dominant disorder in which
      affected patients develop a wide variety of benign and malignant tumors. We
      report here on a 31-week gestational age fetus with pathological features of TSC.
      Developmental expression of hamartin and tuberin in various tissues was studied
      using immunohistochemistry. There was loss of expression of hamartin in the tuber
      and weak expression of the tuberin. Both hamartin and tuberin were expressed in
      bronchial epithelial cells, cardiac muscles, renal collecting tubules, and neural
      tissues. The rhabdomyomas stained negatively for tuberin and hamartin. Two
      genetic loci are responsible for TSC-TSCI and TSC2. The TSC1 gene on chromosome 9
      encodes a protein termed hamartin that lacks sequence similarity to any known
      proteins, whereas the TSC2 gene on chromosome 16 codes for a protein termed
      tuberin. These results indicate that tuberin and hamartin may play a critical
      role in development and thus provide a framework for understanding the
      developmental and hamartomatous manifestations of tuberous sclerosis.

PMID- 16095036
TI  - A rare case of interstitial del(1)(p34.3p36.11) diagnosed prenatally.
AB  - We report a very rare constitutional interstitial deletion of chromosome 1p
      defined within 1p34.3-36.11 bands with an intact pter. The diagnosis was made by
      standard cytogenetics and fluorescence in situ hybridization (FISH) studies on a
      cordocentesis specimen obtained at 21 weeks gestation. Termination of pregnancy
      was performed at 22 weeks gestation due to the ultrasound diagnosis of congenital
      heart disease. Autopsy confirmed congenital heart disease (cardiomegaly,
      Ebstein's anomaly, secundum atrial septal defect, subendocardial fibroelastosis),
      pulmonary lymphangiectasis, a high arched palate, short neck, and bilateral long
      proximally implanted thumbs. To our knowledge, this is the first case of del(1)
      (p34.3p36.11) diagnosed prenatally.

PMID- 16095037
TI  - Congenitally corrected transposition of the great arteries with Ebstein
      malformation and hypoplasia of the aortic arch in a fetus.
AB  - Congenitally corrected transposition of the great arteries is not uncommonly
      associated with Ebstein's malformation of its left-sided tricuspid valve. The
      recognition of this rare association in the fetus is important because its
      postnatal prognosis is guarded. The present case report illustrates fetal
      echocardiographic clues to the diagnosis that include mesocardia and apically
      displaced attachment of the left-sided atrioventricular valve to the ventricular
      septum at four-chamber view.

PMID- 16095038
TI  - Defect in dorso-ventral patterning, asplenia, and conotruncus in a spontaneously
      aborted fetus.
AB  - We describe a very unusual combination, and previously unreported, of
      malformations in an 18-week, spontaneously aborted male fetus. The fetus had a
      reversed dorsoventral positioning of the head and upper limbs relative to the
      body axis with the head and both upper limbs directed dorsally, and an abrupt
      rotation of the vertebral bones at the level of CZ The fetus also had asplenia,
      single ventricle, and conotruncus. The fetus also had flexion deformities at the
      wrist, reduction deformity of the left second digit, anomalies in ossification of
      the bones of the left hand, and bilateral talipes calcaneovalgus. The major
      malformations in this fetus were all blastogenetic in origin and consisted of
      dorsoventral patterning defect involving structures cranial to C7, a laterality,
      and a septation defect of the ventricle and outflow tract of the heart. The
      defects are interpreted as being the result of abnormal coordination of the
      molecular signaling involved in dorsoventral axis formation and laterality of the
      limbs and trunk, and possibly also in cardiac septation.

PMID- 16095039
TI  - An unusual newborn rash.

PMID- 16095040
TI  - Pathology teach and tell: eosinophilic granuloma.

PMID- 16095041
TI  - Renal hypertrophic infundibular stenosis.
AB  - Bilateral hydrocalycosis secondary to radiographically demonstrated bilateral
      infundibular stenosis required a left nephrectomy in an 18-year-old young man.
      The infundibular narrowing was due to marked hyperplasia of the submucosal smooth
      muscle. Scattered within the hypertrophic smooth muscle were rare spindled CD117
      positive interstitial cells, similar to the cells responsible for peristaltic
      pacemaker activity within the gastrointestinal tract. The admixture of CD117
      cells suggests this is a true muscular hyperplasia rather than a leiomyomatosis.
      The stimulus to the hyperplasia is unknown.

PMID- 16095042
TI  - Cue interaction effects in causal judgement: an interpretation in terms of the
      evidential evaluation model.
AB  - In judging the extent to which a cue causes an outcome, judgement can be affected
      by information about other cues that are correlated with the one being judged.
      These cue interaction effects have usually been interpreted in terms of
      associative learning processes. I propose that a different model of causal
      judgement, the evidential evaluation model, offers a viable alternative
      interpretation of cue interaction phenomena. Under the evidential evaluation
      model, instances of contingency information are interpreted as evidence, which is
      confirmatory, disconfirmatory, or irrelevant for the cue being judged. When two
      cues co-occur in a set of instances the evidential value of the instances for one
      of them is determined by three factors: the proportion of confirming instances in
      the set; disambiguation value, which concerns the relation between the set of
      information and prior beliefs about the co-occurring cue; and confirmation value,
      which concerns the relation between the set of information and prior beliefs
      about the cue being judged. Any previous judgement of the cue is then modified in
      the light of these. It is shown that this model can account for all the cue
      interaction phenomena that have been investigated in studies of human causal
      judgement. The model also generates novel predictions, and the results of three
      experiments give support to these predictions. It is also shown that several
      other current models of causal judgement fail to predict a key result from
      Experiment 3.

PMID- 16095043
TI  - Analysis of the learned irrelevance effect in appetitive pavlovian conditioning.
AB  - In Experiments 1 and 2 rats received uncorrelated presentations of a light
      conditioned stimulus (CS) and a food unconditioned stimulus (US) on each day of a
      preexposure phase. Control subjects received the same number of USs during the
      first half of preexposure and the same number of CSs during the second.
      Uncorrelated preexposure retarded inhibitory conditioning. Experiment 3 showed,
      however, that the different patterns of US preexposure experienced by the two
      groups could in itself influence the course of subsequent inhibitory
      conditioning. When this factor was equated by restricting the uncorrelated
      treatment to the first half of the pre-exposure phase (Experiment 2) or by
      extending the control treatment throughout the phase (Experiment 4) it was found
      that uncorrelated preexposure retarded excitatory conditioning, but facilitated
      inhibitory conditioning. This outcome challenges an interpretation in terms of
      the concept of learned irrelevance, which predicts that uncorrelated preexposure
      should retard both forms of conditioning.

PMID- 16095044
TI  - The long-term retention of time: a developmental study.
AB  - Two experiments investigated the age-related changes in long-term retention of
      duration and their effects on time judgement. Children aged 3, 5, and 8 years old
      were given a temporal bisection task with or without a 15-min interfering task
      (Experiment 1), or a retention delay lasting for 0 min, 15 min, or 24 hr
      (Experiment 2) between the presentation of the standard durations and the
      comparison stimulus durations. An interfering task and the increase of the
      retention delay significantly decreased the time sensitivity in the 3- and the 5
      year-olds, and to a greater extent in the younger children, but had no effect in
      the 8-year-olds. This decrease in time sensitivity with the interfering task or
      the retention delay might be due to an increase in the variability of the
      remembered duration.

PMID- 16095045
TI  - Contiguity and the outcome density bias in action-outcome contingency judgements.
AB  - In cause-outcome contingency judgement tasks, judgements often reflect the actual
      contingency but are also influenced by the overall probability of the outcome,
      P(O). Action-outcome instrumental learning tasks can foster a pattern in which
      judgements of positive contingencies become less positive as P(O) increases.
      Variable contiguity between the action and the outcome may produce this bias.
      Experiment 1 recorded judgements of positive contingencies that were largely
      uninfluenced by P(O) using an immediate contiguity procedure. Experiment 2
      directly compared variable versus constant contiguity. The predicted interaction
      between contiguity and P(O) was observed for positive contingencies. These
      results stress the sensitivity of the causal learning mechanism to temporal
      contiguity.

PMID- 16095046
TI  - Urine analysis: old and new algorithms.

PMID- 16095047
TI  - Testicular cancer: the perfect paradigm for marker combinations.

PMID- 16095048
TI  - Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and
      dimethyltryptamine in blood and tissues.
AB  - Bufotenine and N,N-dimethyltryptamine (DMT) are hallucinogenic dimethylated
      indolethylamines (DMIAs) formed from serotonin and tryptamine by the enzyme
      indolethylamine N-methyltransferase (INMT) ubiquitously present in non-neural
      tissues. In mammals, endogenous bufotenine and DMT have been identified only in
      human urine. The DMIAs bind effectively to 5HT receptors and their administration
      causes a variety of autonomic effects, which may reflect their actual
      physiological function. Endogenous levels of bufotenine and DMT in blood and a
      number of animal and human tissues were determined using highly sensitive and
      specific quantitative mass spectrometric techniques. A new finding was the
      detection of large amounts of bufotenine in stools, which may be an indication of
      its role in intestinal function. It is suggested that fecal and urinary
      bufotenine originate from epithelial cells of the intestine and the kidney,
      respectively, although the possibility of their synthesis by intestinal bacteria
      cannot be excluded. Only small amounts of the DMIAs were found in somatic or
      neural tissues and none in blood. This can be explained by rapid catabolism of
      the DMIAs by mitochondrial monoamino-oxidase or by the fact that the dimethylated
      products of serotonin and tryptamine are not formed in significant amounts in
      most mammalian tissues despite the widespread presence of INMT in tissues.

PMID- 16095049
TI  - Markers of endothelial cell activation in elderly men at high risk for coronary
      heart disease.
AB  - OBJECTIVE: Circulating cell adhesion molecules (CAMS) are regarded as
      inflammatory markers related to the process of atherosclerosis and cardiovascular
      disease (CVD). In the haemostatic system, elevated levels of thrombomodulin (TM),
      von Willebrand factor (vWF) and tissue-type plasminogen activator antigen (tPAag)
      have likewise been associated with atherothrombotic cardiovascular disease
      states. MATERIAL AND METHODS: Levels of these circulating markers were
      investigated in a cross-sectional study including 563 men aged 70 (64-76) years
      characterized as hypercholesterolaemic in 1972, as related to the following
      clinical entities: cardiovascular morbidity (28%), diabetes (15%), hypertension
      (70%) and smoking habits (34%) after 24 years. RESULTS: In patients presenting
      with CVD, significantly higher levels of tPAag were encountered (12.9 versus 12.0
      ng/ml, p = 0.02). In smokers, levels of sICAM-1 were significantly higher (331
      versus 298 ng/ml, p < 0.001), whereas levels of sVCAM-1 and sTM were lower
      compared with those in non-smokers (543 versus 582 ng/ml, p = 0.01, 40.6 versus
      44.5 ng/ml, p < 0.01, respectively). In diabetics, levels of sE-selectin and
      tPAag were significantly higher than those in non-diabetics (55.9 versus 45.7
      ng/ml, p < 0.001, 13.6 versus 12.0, p = 0.001, respectively). In subjects with
      hypertension, levels of TM were elevated (44.0 versus 40.8 ng/ml, p = 0.03). In
      multivariate regression analyses, tPAag remained significantly associated with
      the presence of CVD (p = 0.03), sE-selectin with diabetes (p=0.004), sTM with
      hypertension (p = 0.02) and sVCAM-1, sICAM-1 and sTM with smoking, (p = 0.01, p <
      0.001, p < 0.001, respectively). CONCLUSIONS: The present results may contribute
      to the understanding of the multitude of factors influencing these endothelial
      markers and their evaluation in various disease entities.

PMID- 16095050
TI  - Increase in plasma calprotectin during long-distance running.
AB  - Running leads to biochemical and hematological changes consistent with an
      inflammatory reaction to tissue injury. We report changes in the plasma
      concentration of the leukocyte-derived protein calprotectin after long-distance
      running. Blood samples were collected from runners before and after a marathon,
      half-marathon, a 30-km cross-country run, a military ranger-training course and
      short-term maximal physical exercise until exhaustion, VO2max. Leukocyte counts,
      plasma calprotectin concentration and calprotectin per neutrophilic granulocyte
      were assayed using a new method. During the marathon, half-marathon, the 30-km
      run, the ranger-training course and the VO2max exercise, calprotectin levels
      increased 96.3-fold, 13.3-fold, 20.1-fold, 7.5-fold and 3.4-fold, respectively.
      These changes may reflect damage to the tissues or vascular endothelium, causing
      microthrombi with subsequent activation of neutrophils. These cells are known to
      phagocytose platelets in microthrombi and may contribute to the prevention of
      clinical thrombosis. The half-life of calprotectin in plasma was about 5 h. The
      content of calprotectin per neutrophil remained unchanged during exercise at a
      level similar to that in healthy blood donors: mean: 25 pg/cell, range 18.8-33.6.
      A reference interval (mean +/- 2 SD) of 18.6-31.4 pg/cell is suggested.

PMID- 16095051
TI  - Nickel contamination from an intravenous catheter used for infusion.
AB  - At the outset of a clinical research project involving metal analyses on patients
      receiving metal devices in conjunction with hip fractures, unexpected high
      concentrations of nickel were discovered in serum samples taken before surgery.
      The median nickel concentration in 30 patients was 4.6 microg/l (highest 19.5
      microg/l), while reference values in non-exposed persons are reported to be 0.05
      1.2 microg/l. The sampling and analyzing procedures were scrutinized without
      positive identification of the source of contamination. A review of all relevant
      procedures was then undertaken. It was identified that the nickel contamination
      originated from the intravenous catheter which was always put in place
      immediately after the patient's admission to the hospital, and thus before the
      blood sampling. Close inspection of the intravenous catheter revealed that it
      contained a nickel-plated brass funnel inside the hub of the device which
      released nickel into the Ringer-acetate passing through the catheter. The present
      catheter has been the standard device used at Haukeland University Hospital for
      the past 6 years. Patients have consequently been exposed to small amounts of
      nickel. The clinical relevance of the exposure cannot be determined. For the
      patients included in the research project, a metal-free alternative was used.
      These findings show that the quality and properties of everyday medical devices
      should be scrutinized, at least before being used for special purposes.

PMID- 16095052
TI  - Expression and characterization of six clinically relevant uroporphyrinogen
      decarboxylase gene mutations.
AB  - The functional consequence of six uroporphyrinogen decarboxylase (UROD) gene
      mutations found in Danish patients with familial porphyria cutanea tarda was
      investigated. Wild-type UROD and the 6 mutants (3 missense, 1 nonsense and 2
      frameshift mutants) were cloned and expressed using the prokaryotic gGEX-6P
      system, in which the protein is produced in fusion with glutathione S-transferase
      (GST). Enzymatic activity of the purified recombinant mutant fusion proteins
      ranged from undetectable to less than 12% of the recombinant wild-type protein.
      Mutant proteins cleaved from the GST part did not retain any catalytic activity.
      These observations can be ascribed to the structure/function relationships of the
      enzyme, and the fact that the enzyme is a dimer in its active form. Although the
      clinical manifestation of familial porphyria cutanea tarda is complex, the
      findings support the notion that different mutations may affect individuals
      differently.

PMID- 16095053
TI  - Bacterial antigen induced release of soluble vascular endothelial growth factor
      (VEGF) and VEGFR1 before and after surgery.
AB  - OBJECTIVE: The influence of surgery on release of soluble vascular endothelial
      growth factor (sVEGF) and the soluble inhibitory receptor (sVEGFR1) is unknown.
      The effect of major and minor surgery on variations in sVEGF and sVEGFR1
      concentrations in vivo was studied, and on bacterial antigen-induced release of
      sVEGF and sVEGFR1 from whole blood in vitro. MATERIAL AND METHODS: Sixty-one
      patients with abdominal diseases undergoing five different surgical procedures
      were included in the study. Blood samples were drawn from patients before and
      after the operation. White blood cells and platelets were counted, and plasma
      sVEGF and sVEGFR1 were determined. Whole blood from each blood sample was
      stimulated in vitro with bacteria-derived antigens (lipopolysaccharides or
      protein A) and sVEGF and sVEGFR1 levels were subsequently determined in the
      supernatants. RESULTS: Neither sVEGF nor sVEGFR1 concentrations in plasma changed
      during surgery. In vitro stimulation of blood samples with bacteria-derived
      antigens resulted in a significant increase in sVEGF (p < 0.0001) and a less
      pronounced but still significant increase in sVEGFR1 (p < 0.01). Bacterial
      antigen-induced release of sVEGF correlated significantly with neutrophil cell
      counts (0.53 < r < 0.78; p < 0.0001). Bacterial antigen-induced sVEGFR1 release
      did not correlate with cell counts. CONCLUSIONS: Plasma sVEGF and sVEGFR1
      concentrations did not change during surgery. In vitro bacterial stimulation led
      to increased release of sVEGF, which was not compensated for by an equivalent
      increase in sVEGFR1. There was a positive impact of major abdominal surgery on
      release of sVEGF. The bacterial antigen-induced changes in sVEGF may be related
      to the number of circulating neutrophils.

PMID- 16095054
TI  - Urinary excretion of aquaporin-2 after furosemide and felodipine in healthy
      humans.
AB  - OBJECTIVE: Furosemide inhibits renal sodium and chloride reabsorption in the loop
      of Henle. A compensatory increased reabsorption of sodium and water takes place
      in the collecting duct. It is not known whether aquaporin-2 (AQP2) renal water
      channels are involved in this compensatory reabsorption. In animals,
      dihydropyridine derivatives of calcium channel blockers down-regulate AQP2 in the
      collecting duct, but the effect has not been studied in humans. We sought to test
      the hypotheses that urinary excretion of aquaporin-2 (U-AQP2) increases after a
      single intravenous dose of furosemide, and that U-AQP2 decreases after a single
      oral dose of felodipine. MATERIAL AND METHODS: In two randomized, single-blind,
      placebo-controlled, cross-over studies, we measured the effect of furosemide and
      felodipine on U-AQP2, urine volume, free water clearance (CH2O), and fractional
      excretion of sodium (FENa) in 13 healthy subjects in each study. Plasma
      concentrations of vasopressin (AVP), renin (PRC), angiotensin II (ang II),
      aldosterone (aldo), atrial (ANP), and brain natriuretic peptides (BNP) were
      measured during the study. Glomerular filtration rate (GFR) was measured by
      constant infusion technique. U-AQP2 and hormones were determined by
      radioimmunoassay. RESULTS: Furosemide treatment increased U-AQP2 (202%), urine
      volume (214%), and FENa by a factor of 11, (p < 0.001 for all), whereas CH2O and
      GFR were unchanged. After treatment with placebo, no differences were seen.
      Furosemide treatment increased AVP (18%), PRC (60%), ang II (100%), and aldo
      (98%) (p < 0.032); ANP was decreased by 29% (p < 0.001), whereas there was no
      change in BNP. The hormones were unchanged after placebo except for a minor
      decrease in ANP after placebo. Felodipine tended to increase U-AQP2, to decrease
      CH2O and urine volume and GFR, and to increase FENa, but the effect was not
      significantly different from placebo. Felodipine increased PRC (82%) (p < 0.003)
      and ang II, but decreased aldo, and increased AVP. After placebo, PRC was
      unchanged, whereas ang II, aldo and AVP were changed as after felodipine.
      CONCLUSIONS: Furosemide treatment increased U-AQP2, AVP, and the activity of the
      renin-angiotensin-aldosterone system. These changes are most likely compensatory
      phenomena, which prevent an excess loss of sodium and water. Felodipine tended to
      increase U-AQP2.

PMID- 16095055
TI  - Research in general dental practice.
AB  - Spurred by an initiative by the National Institute of Dental and Craniofacial
      Research in the USA, this article presents the need for a change in clinical
      dental research towards practice-based research. It outlines the shortcomings of
      past and present-day research in dentistry, with emphasis on the lack of clinical
      relevance of much of the research performed. The slow transfer of sound research
      findings to clinical practice is also a major problem. The article reviews some
      problems related to restorative dentistry and how they have adversely affected
      general dental practice. Practice-based research places emphasis on the problems
      experienced by clinicians in the routine care of patients. Clinicians should be
      linked together in research networks. The problems they face in dental practice
      and the clinical experience they have will form the basis for studies by the
      network. Experienced clinical researchers will provide guidance and statistical
      support for the studies initiated by the clinicians.

PMID- 16095056
TI  - Oral health-related knowledge, attitudes, and beliefs among 11 to 12-year-old
      Finnish schoolchildren with different oral health behaviors.
AB  - The aim of this study was to explore oral health-related knowledge, attitudes,
      and beliefs among 11 to 12-year-old schoolchildren with favorable, moderate, or
      poor behavior related to oral health. The data were gathered by questionnaire.
      Recommendations commonly used in Finland in oral health education were chosen as
      the criteria for selection of groups of children with favorable, moderate, and
      poor oral health behavior. Differences between groups were analyzed using
      crosstabulations and factors related to unfavorable behavior using logistic
      regression analysis. The percentage of children with appropriate knowledge was
      higher in the good behavior group (GB) than in the other groups. The groups
      differed most in the children's knowledge of the recommendation to use fluoride
      toothpaste at least twice a day. Most children in the GB group considered it
      important to brush their teeth for the fresh feeling this gave. The majority of
      children in all groups considered it important to brush their teeth when going to
      the dentist. The majority also considered brushing important for avoiding tooth
      decay and tooth discoloration as well as for having fresh breath. Unfavorable
      knowledge, attitudes, beliefs, and behavior tended to accumulate in the same
      children. Factors associated with unfavorable behavior were male sex, mother's
      low skill occupation level, and child's poor knowledge of oral health-related
      facts.

PMID- 16095057
TI  - Protein profile of pepsin-digested carious and sound human dentine.
AB  - The purpose of this study was to describe the protein profile of pepsin-digested
      carious and sound dentine using sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE). Carious and sound dentine powder was decalcified
      using 10% EDTA at pH 7.4 for 48 h. The decalcified pellet was digested using
      pepsin at pH 2 under sequenced conditions: at 4 degrees C for 24 h, a further 24
      h at 23 degrees C, and finally for 24 h at 37 degrees C. After every step, the
      soluble fraction was separated by centrifugation and analyzed in 15% SDS-PAGE.
      Two bands at 56 and 62 kDa could be observed in carious dentine digests and were
      considered specific carious bands. Similar bands could be observed in sound
      dentine samples, but only after pepsin digestion at higher temperatures (23
      degrees C and 37 degrees C). Pepsin digests non-helical collagen and the triple
      helix structure of collagen is lost when the temperature rises. The bands at 56
      and 62 kDa in sound dentine specimens thus represent pepsin-cleaved collagen.
      There is a possibility that the specific carious bands in carious dentine
      represent collagen decomposed in a manner similar to the way pepsin digests
      native dentine collagen at 23 degrees C and 37 degrees C.

PMID- 16095058
TI  - Levels of mutans streptococci and lactobacilli in plaque on aged restorations of
      an ion-releasing and a universal hybrid composite resin.
AB  - The purpose of this in vivo study was to evaluate the cariogenic microflora of
      plaque on aged restorations of a hydroxyl, fluoride, and calcium ion-releasing
      composite resin (IRCR) (Ariston pHc), and to compare it intra-individually with a
      universal hybrid composite resin and enamel. Each of 19 subjects received one
      proximal restoration of the IRCR, one proximal universal hybrid composite resin
      restoration (CR) and each subject had one non-filled proximal enamel control
      surface to make intra-individual comparisons possible. To avoid peak ion releases
      from the materials, aged restorations were studied. Plaque was collected from 57
      surfaces using sterile applicator tips. Samples were cultured to determine the
      numbers of mutans streptococci, lactobacilli, and total microorganisms. The
      relative numbers for mutans streptococci (% of total bacteria) were: IRCR 0.59%,
      CR 0.40%, enamel 0.22%. Two outliers were found in the IRCR group. Excluding
      these outliers resulted in a relative number of 0.33%. Lactobacilli were detected
      in the plaque from only 9 surfaces and at very low relative proportions for all
      three surfaces: 0.01%. The enamel surfaces showed the lowest relative numbers of
      mutans streptococci and lactobacilli, but the differences were not significant.
      It can be concluded that the ion release of the IRCR did not influence the growth
      of cariogenic microorganisms in dental plaque.

PMID- 16095059
TI  - Clinical performance of DIAGnodent in the detection of secondary carious lesions.
AB  - The diagnostic value of DIAGNOdent in detecting primary occlusal caries has been
      investigated in many studies, although its use in in vivo detection of secondary
      caries remains unclear. The aim of this study was to investigate the ability of
      DIAGNOdent in in vivo detection of secondary caries on teeth with amalgam
      restorations. The material comprised 51 posterior teeth restored with amalgam
      material. Bitewing radiographs were taken of all teeth, in accordance with the
      standard clinical protocol, and analysed by five observers with respect to
      secondary caries. The restoration margins of each tooth were carefully scanned
      with DIAGNOdent and the site of the highest reading and its value were registered
      in a digital picture. The color (stained/unstained) of the restoration margins
      was also documented. The restoration material was removed and all cavities were
      examined carefully by two observers together, both visually and by probe. The
      results showed that the sensitivity and specificity of DIAGNOdent and
      conventional radiography in detecting secondary caries were 0.60/0.81 and
      0.56/0.92, respectively. For DIAGNOdent, 100% of the teeth in the false-positive
      fraction had stains. Regarding receiver operating characteristic analyses, the Az
      values were 0.78 and 0.69 for DIAGNOdent and radiography, respectively. We
      conclude that DIAGNOdent may be used only as an adjunct to conventional methods
      in detecting secondary caries on teeth with amalgam restorations.

PMID- 16095060
TI  - Effect of storage duration on tensile bond strength of acrylic or silicone-based
      soft denture liners to a processed denture base polymer.
AB  - OBJECTIVE: To investigate the effect of storage duration on the tensile bond
      strength of acrylic and silicone-based denture base materials with liners either
      heat-cured or auto-cured. MATERIAL AND METHODS: The denture liners investigated
      were Vertex soft (acrylic-based, heat-cured), Coe soft (acrylic-based, auto
      cured), Molloplast-B (silicone-based, heat-cured), and Mollosil plus (silicone
      based, auto-cured). The soft liner specimens were 10 x 10 x 3 mm and were
      processed between two PMMA blocks. They were tested following immersion in water
      at 37 degrees C for 1 day, 1 week, and 1, 3, and 6 months. Tensile bond strength
      was measured using a universal testing machine (Testometric Micro 500) at a
      crosshead speed of 20 mm/min (n = 10 specimens per experimental group). Multiple
      ANOVA and Tukey HSD were used to analyse the data at a pre-set alpha of 0.05.
      RESULTS: The results indicate that the tensile bond strength of acrylic-based
      soft liners is greater than that of silicone-based materials. The bond strength
      of all lining materials decreases with storage duration; the decrease being
      greatest for the acrylic-based soft liners. The decrease in bond strength of the
      auto-cured materials is greater than that of the heat-cured products. CLINICAL
      SIGNIFICANCE: Comparison of the materials in this study indicates that the
      silicone-based, heat-cured soft liner is superior, based on the tensile bond
      strength property. Use of silicone-based, heat-cured soft liners may provide
      better clinical success over a long period. These laboratory results need to be
      verified by clinical testing.

PMID- 16095061
TI  - Developing a scale for measuring expectancy of retaining natural teeth for life
      and comparison of results obtained using a global item and a multi-item scale of
      measurement.
AB  - OBJECTIVE: To develop and test a scale for measuring expectancy of retaining
      teeth for life and to compare the estimates when using a global item with those
      obtained with a multi-item scale of measurement. MATERIAL AND METHODS: The design
      of the study was cross-sectional selected and random sample surveys using a self
      administered questionnaire or interview. There were two groups of patients and a
      national sample aged 16-79 years (n=1274); response rate 64%. The main results
      pertain to dentate subjects in a global group (n=615) and in a scale group
      (n=609). The outcome measure was expectancy of retaining natural teeth for life.
      Results. When using the global item, 92% (95% CL 89.8, 94.1) of the respondents
      believed they would definitely or possibly retain their natural teeth for life,
      significantly higher than the 81% (95% CL 77.6, 84.0) obtained with the 4-item
      conditional scale. Cronbach's alpha was 0.89 for the 4-item scale and the test
      retest reliability moderate (kappa = 0.51; 0.77 for +/-1). The adults' belief in
      retaining teeth for life was significantly associated with having a live-in
      partner (p = 0.009) when the global question was the dependent variable; and sex
      (p = 0.000) and education (p = 0.004) when the 4-item scale was the dependent
      variable. Explained variance was 3.8% and 4.5%, respectively. Conclusions. The
      internal reliability of the 4-item scale was high. A significantly lower
      proportion of people reported belief in retaining natural teeth for life when
      employing the 4-item conditional scale than when the unconditional global
      question was used.

PMID- 16095062
TI  - Tramadol premedication in operative extraction of the mandibular third molar: a
      placebo-controlled crossover study.
AB  - Anxiolytic drugs are widely used for premedication in oral surgery. Since anxiety
      is usually associated with the fear of pain, we tested the effects of the
      analgesic tramadol in premedication before operative extraction of the mandibular
      third molar under local anesthesia. In a double-blind crossover study, 20
      patients were randomized to receive 100 mg oral tramadol or placebo 1 h before
      operation. Anxiety, nausea, dryness of the mouth, pain and discomfort were
      recorded before administration of the drug, immediately before and after
      operation, and 0.5, 1, and 2 h postoperatively using ungraded 0-100 mm VAS
      scales. Blood pressure and heart rate were measured at the same times; vigilance
      was tested using the Maddox Wing Test and sensorimotor performance using the
      Trieger Dot Test; hemoglobin oxygen saturation (SpO2) was measured using a pulse
      oximeter. In addition, SpO2 and heart rate were recorded continuously in nine
      patients using a pulse oximeter connected to a computer. The surgeon assessed the
      quality of operating conditions on the VAS scale. Tramadol delayed and decreased
      the need of analgesics on the day of operation (p < 0.05). The operating
      conditions were better in patients on tramadol premedication than in those on
      placebo during the first operation (p < 0.05), but no differences were seen in
      patient well-being between treatments. The second operation was less stressful
      than the first. Tramadol is recommended only with special indications for
      premedication of patients undergoing third molar extraction under local
      anesthesia.

PMID- 16095063
TI  - Oral health of homeless adults in Stockholm, Sweden.
AB  - The aim of the present study was to record and describe the oral condition of
      homeless adults in Stockholm, Sweden. There have been no clinical studies of the
      oral health of the homeless in Sweden since the 1970s. The study population
      comprised 147 homeless individuals (110 M, 37 F) in the age range 22-77 years.
      All underwent oral examination, including registration of periodontal status and
      caries data. The results show that homeless adults in Stockholm have fewer
      remaining teeth than the general population. Because conservative periodontal
      treatment is expensive and time-consuming, teeth with doubtful prognoses are
      usually extracted and only those with optimal periodontal health are retained.
      Another consequence of inadequate periodontal treatment, including insufficient
      oral hygiene instruction, is the high percentage of tooth surfaces with plaque
      accumulation. Heavy plaque accumulation will also have an effect on caries
      progression, expressed in this study as high DMFT values. Loss of teeth is likely
      to create dental and chewing problems, possibly resulting in increased dental and
      medical treatment needs.

PMID- 16095064
TI  - Prevalence of dental fluorosis in children from non-water-fluoridated Halmstad,
      Sweden: fluoride toothpaste use in infancy.
AB  - OBJECTIVES: To determine the prevalence and severity of dental fluorosis in
      children aged 7-9 years from non-water-fluoridated Halmstad, Sweden, and to
      relate the results to their reported fluoride exposure history during infancy.
      MATERIAL AND METHODS: In Spring 2002, a questionnaire distributed to a cluster
      random sample of 1039 parents enquired into their child's early oral health
      behaviors and included a "photographic toothpaste menu". The permanent upper
      anterior teeth (13-23) were examined clinically (+10% repeats) using a modified
      Thylstrup-Fejerskov Index. RESULTS: Complete data were available for 53% (n=548)
      of the sampled children. The prevalence offluorosis at any level was 49% (95% CI:
      45-54%), and of fluorosis with esthetic concern (TF score > or =3) 4% (95% CI: 3
      6%). Based on repeat observations, reliability was good (kappa = 0.82). There was
      no statistically significant increased risk of dental fluorosis prevalence
      associated with any of the fluoride exposure risk factors examined, including
      reported usage of (1000 ppm) fluoride toothpaste from time of first deciduous
      tooth eruption. CONCLUSIONS: While there were low levels of dental fluorosis of
      esthetic concern, half the children had some degree of dental fluorosis. The
      prevalence of dental fluorosis was not explained by the risk factors, including
      fluoride toothpaste usage as explored in this study.

PMID- 16095065
TI  - [I Brazilian guidelines on diagnosis and treatment of metabolic syndrome].

PMID- 16095066
TI  - Astrology and medicine in later Medieval England the calendars of John Somer and
      Nicholas of Lynn.

PMID- 16095067
TI  - [A physician and his image of the 16th century? Nicolaus Gugler of Nuremberg].

PMID- 16095068
TI  - [Origin of psychiatric disorders ex sexualibus: explanatory approaches at the
      beginning of the 19th century].
AB  - In the first half of the 19th century there were the first publications, which
      dealt systematically with the relation between deviations of the sexual system or
      behaviour and mental disturbances. The knowledge and the theoretical ideas of
      medicine and of psychiatric diseases at that time and a discussion concerning the
      consequences of masturbation can be demonstrated in works like "De mentis
      aberrationibus ex partium sexualium conditione abnormi oriundis" by Hermann
      Joseph Lowenstein (1823) and "Ueber die Beziehungen des Sexualsystemes zur Psyche
      uberhaupt und zum Cretinismus ins Besondere" by Joseph Haussler (1826). Both
      publications try to sytemize the issue and prove their hypotheses by numerous
      casuistics. The autors belong to the so called "Somatis School" in psychiatry at
      that time.

PMID- 16095069
TI  - [The issue of continuity in ancient horse medicine: the treatment of diseases of
      the extremities described in the Kitab al-furusiya wa-l-baytara by Muhammad ibn
      Ya'qub ibn ahi Hizam al-Huttuli].
AB  - Since the late 9th century, scientific literature in Arabian language, based on
      the translation and compilation of works of the Classical, Persian and Indian
      culture considerably increased. This also applies to the field of veterinary
      medicine, as is illustrated by a number of hippological and hippiatric treatises.
      Affinities between texts on horse medicine in Antiquity and in Arabian literature
      have been mentioned by philologists, but the degree of dependence on classical
      texts could not be verified due to the lack of translations of the Arabian texts.
      In this respect, the oldest available text about hippology and hippiatry, the
      Kitab al-furusiya wa-l-baytara written by Muhammad ibn Ya'qub ibn ahi equerry at
      the court of caliph al-Mu'tasim, al-Mutawakkil or al-Mu 'tadid during the second
      half of the 9th century, is of particular importance. In this contribution we
      focus upon seven major diseases affecting the distal extremities in horses. The
      contents have been analysed from an historical and a medical point of view and
      compared with those from a representative selection of medieval treatises that
      circulated in the Mediterranean region and the Orient up to the 14'h century.
      This comparison reveals obvious similarities between ibn ahi Hizams text and
      later hippiatric treatises, written in medieval Arabic. Parallels to the texts of
      the authors of the late Antiquity and the medieval Occident, however, can not be
      observed. The Kitab al-furusiya wa-l-baytara thus evidences that Arabian
      hippiatry had its own tradition, at least when dealing with the diseases of the
      extremities.

PMID- 16095070
TI  - [Hildegards von Bingen 'Liber simplicis medicinae' in the Mainz 'Garden of
      Health'].
AB  - The "Garden of Health" (Gart der Gesundheit) is the first illustrated book of
      herbs in German language. Its author, Johann Wonnecke from Kaub on the Rhine, was
      born in 1430 and worked as a city doctor in Frankfurt/Main until his death in
      1503 or 1504. In his book, he refers to "proven Greek, Latin and Arabic masters
      of medicine" (bewerte meister in der artzeney), whose writings he was instructed
      to collect by Bernard von Breidenbach in 1480. Wonnecke carried out he task in a
      special way, deceiving five generations of historians of science, who proceeded
      from the false assumption, that the Gart der Gesundheit was compiled and
      translated from Latin sources. Wonnecke established the desired authors skilfully
      in his report, but under a more detailed investigation they reveal themselves as
      not taken from Latin sources but copied off from native language scriptures, e.g.
      Alterer deutscher Macer and Buch der Natur by Konrad von Megenberg. To these
      hitherto known sources used by him now the Speyrer Krauterbuch is added, which
      supplied the medical knowledge of Hildegard von Bingen to the "Gart".

PMID- 16095071
TI  - What is a referral?
AB  - Obtaining a referral from a primary care physician to see a specialist is a
      common experience among patients. Differing definitions of what it means to "have
      a referral, "however, can lead to gaps between the service provided by the
      specialist and the expectations of the patients. Empirical research illustrates
      these varying definitions of "having a referral" among potential patients. The
      extent of confusion among a presumably educated sample of the patient population
      suggests that medical group managers should conduct a marketing audit of their
      policies and procedures to ensure that gaps in service delivery are removed.

PMID- 16095072
TI  - Using an employee handbook to head off problems.
AB  - Most medical practices agree that an employee handbook is a great idea. Many,
      however, don't know how to write a good handbook. This article provides a helpful
      overview of the kinds of materials that should and should not be included in your
      practice's employee handbook. It explores the many benefits of employee handbooks
      and identifies four policy topics that you should avoid. It suggests the benefits
      and potential uses of a glossary in your employee handbook and provides an
      example of the terms that might be included in a medical practice glossary. This
      article also suggests the appropriate language and tone for employee handbooks
      and offers advice about distributing them so your staff will read and understand
      your personnel policies. Finally, the article offers a blueprint for creating
      your own employee handbook.

PMID- 16095073
TI  - The physician's no. 1 financial mistake: a flawed relationship with professional
      advisors--why you're not getting the advice you should.
AB  - In spite of their high level of medical education, physicians are relatively
      unschooled in administering their financial affairs. They most frequently make
      uninformed choices in their selection of professional advisors. In this article,
      the authors discuss what constitute the most grievous errors in this selection
      process.

PMID- 16095074
TI  - Computer briefs: practicing safe computing.

PMID- 16095076
TI  - Reading and understanding financial statements.
AB  - Feeling comfortable reading and understanding financial statements is critical to
      the success of healthcare executives and physicians involved in management.
      Businesses use three primary financial statements: a balance sheet represents the
      equation, Assets = Liabilities + Equity; an income statement represents the
      equation, Revenues - Expenses = Net Income; a statement of cash flows reports all
      sources and uses of cash during the represented period. The balance sheet
      expresses financial indicators at one particular moment in time, whereas the
      income statement and the statement of cash flows show activity that occurred over
      a stretch of time. Additional information is disclosed in attached footnotes and
      other supplementary materials. There are two ways to prepare financial
      statements. Cash-basis accounting recognizes revenue when it is received and
      expenses when they are paid. Accrual-basis accounting recognizes revenue when it
      is earned and expenses when they are incurred. Although cash-basis is acceptable,
      periodically using the accrual method reveals important information about
      receivables and liabilities that could otherwise remain hidden. Become more
      engaged with your financial statements by spending time reading them, tracking
      key performance indicators, and asking accountants and financial advisors
      questions. This will help you better understand your business and build a
      successful future.

PMID- 16095075
TI  - The facility's role in office economics: the bottom line.
AB  - The object of medical practice is to deliver services in a timely manner. To
      prosper in the current environment, clinicians must stress productivity and
      efficiency. This article discusses the impact of office space configuration on
      these factors. Not only is profitability increased, satisfaction improves as
      providers can spend more face-to-face time with patients, and waits are reduced.

PMID- 16095077
TI  - How to get a good night's sleep: adhere to correct billing practices.

PMID- 16095078
TI  - The False Claims Act: the courts move toward a rule of reason.
AB  - Physicians have been concerned that the False Claims Act may be invoked
      recklessly, and that they are at the mercy of whistleblowers in their own midst
      or from the outside who may act in revenge or pique. This article discusses the
      evolution of case law involving medical practices and reimbursement issues that
      deal with government payment regulations. It indicates the limitations that are
      imposed on prosecutors, as well as the liability that providers do incur under
      current statues.

PMID- 16095079
TI  - Legal aspects of physician recruitment.
AB  - It's no secret that recruiting a new physician to your practice is a difficult
      task. Depending on your medical specialty, it may take two years and possibly
      longer to recruit the right person. This article addresses some of the key steps
      you can take now to overcome obstacles in the recruiting process.

PMID- 16095080
TI  - The 15 most common coding/billing errors.

PMID- 16095081
TI  - Assessing the challenges for 2005.

PMID- 16095082
TI  - Federal tax: is there anything for us in the new domestic production activities
      deduction?

PMID- 16095083
TI  - Trends in the consumer price index.

PMID- 16095085
TI  - [Treatment results in external and middle ear malignant neoplasms of patients
      treated at the Laryngology Department of Medical University of Silesia between
      1991-2001].
AB  - The authors present 18 patients with malignant neoplasms of the ear and temporal
      bone who were treated in the Clinic of Laryngology Medical University of Silesia
      in Katowice in the years 1991-2001. The most frequent was squamous cell carcinoma
      (11 patients--61%). The neoplasm was located on the auricle in 7 patients (39%),
      in the external auditory canal in 4 (22%) patients, in the middle ear in 5
      patients (28%) and in 2 cases (11%) it was difficult to establish primary site.
      Ten patients (55.5%) were treated in stage T4. All patients had surgery and in
      advanced cases the radiotherapy was added. The best outcomes were in auricular
      neoplasms. The treatment results were much worse in neoplasms of the external
      auditory canal and the middle ear. Over 3 year follow-up in 10 patients (55%)
      with ear and temporal bone neoplasms shows no recurrence.

PMID- 16095084
TI  - [The evolution of epidemiology and clinical characteristics of laryngeal and
      hypopharyngeal carcinoma in Poland from 1991 to 2001].
AB  - On the base of retrospective analysis of 12,888 cases of carcinoma of larynx and
      hypopharynx, diagnosed in 19 ENT Departments in Poland from 1991 to 2001, the
      assessment of basic epidemiological data, including the localization of tumor and
      stage of local and clinical advancement of the disease at the time of diagnosis
      has been conducted. In analyzed period of 11 years the trends to change of the
      mentioned above parameters has been examined. The significant increase of female
      patients in this period was observed, with average proportion M:F = 8:1. The
      glottis localization of carcinoma dominated (47.6%), followed by supraglottis
      (40.8%) and pyriform fossa (7.8%), with significant increase of pyriform fossa
      tumors in the analyzed period of 11 years. In the majority of cases the carcinoma
      of larynx and hypopharynx was diagnosed in the advanced stage (T3 + T4) of local
      disease, with the highest percentage in localization within the pyriform fossa
      (81.0%), and the lowest percentage in glottis tumors (45.6%). The regional lymph
      nodes metastases has been diagnosed in 46.7% of the analyzed group, with the
      highest percentage in tumors localized in pyriform fossa (82.9%), and the lowest
      percentage in tumors of glottis localization (33.1%). In the 11 years time the
      significant drop down of N0 cases and tendency to increase of N2 and N3 in the
      supraglottis localization of tumor. The distant metastases in the analyzed group
      at the time of diagnosis has been registered in 2.0%, with the highest percentage
      in posterior pharyngeal wall (7.6%) and pyriform fossa (7.4%). The authors
      postulate the renewal of prospective study on epidemiology, clinical
      characteristics and treatment results of larynx and hypopharynx carcinoma in
      Poland.

PMID- 16095086
TI  - [Sphenoid sinus surgery].
AB  - Sphenoid sinus surgery due to specific localization is placed in
      otolaryngologists and neurosurgeons field of interest. Surgery of this area, from
      one side, causes number of problems, which usually arise due to close
      neighbourhood of important structures, but on the other, serves as alternative
      approach, eliminating necessity of extended operations with craniotomies. The
      article summarizes results of sphenoid sinus surgery at ENT Department,
      University of Medical Sciences in Poznan between 1990 and 2003, as well as points
      out characteristic features of the surgery in this specific localization.

PMID- 16095087
TI  - [Autofluorescence laryngoscopy in the diagnosis of laryngeal cancer--early
      results].
AB  - BACKGROUND: During oncogenesis significant changes in tissue properties occur
      that result in alteration of fluorescence characteristics of the tissue. The aim
      of our study was to determine the usefulness of autofluorescence technique in
      diagnostic of laryngeal epithelium lesions. MATERIAL AND METHODS: 40 patients
      admitted to the Department of Otolaryngology Wroclaw Medical University due to
      different laryngeal lesions were included into the study. They underwent white
      light laryngoscopy followed by autofluorescence videoendoscopy. AF was induced by
      blue light of xenon short arc lamp and processed by a D-light AF System (Storz).
      Autofluorescence and white light images were immediately assessed and later
      compared with to histopathological findings. RESULTS: Normal laryngeal mucosa
      showed a typical green fluorescence signal. Squamous cell carcinoma displayed a
      diminished green fluorescence and in some cases presented reddish-yellow color.
      CONCLUSIONS: We revealed that autofluorescence laryngoscopy is very helpful,
      supplementary tool in diagnosis of laryngeal pathology. Autofluorescence
      laryngoscopy is noninvasive technique designed especially for diagnostic of early
      and premalignant lesions.

PMID- 16095088
TI  - [Localisation and direction of spread in oral and oropharyngeal cancer in the
      material of Head and Neck Oncological Surgery Department, University of Medical
      Sciences in Poznan].
AB  - The directions of tumor spread are determined by the anatomy of the affected
      organ. The vessel, nerve anatomy and presence of structures, that may potentially
      constitute a barrier for spread out of the tumor are of crucial importance. The
      aim of this paper was to presentation of the spreading directions of oral cavity
      and oropharyngeal squamous cell cancer based on the own experience. Material
      include 163 patients surgically treated between 2003-2003 in Department of ENT,
      Head and Neck Oncological Surgery Department in Poznan. The examination was
      conducted on the base of retrospective analysis of ambulatory charts and the
      hospital files. RESULTS: 163 (90%) patients were operated for primary oral and
      oropharyngeal cancer. The primary localization included in the palatine tonsil
      (82 patients), trunk of the tongue (48 patients) and floor of the mouth (20
      patients) were predominated. The spread directions included: floor of the mouth
      (36) soft palate (35), base of tongue (33), hypopharynx (20) and trunk of tongue
      (16). The 31 crossed the midline, 27 infiltrated the tonsillopalatine angle, 9
      retromolar area and 3 the mucosa of the cheek. Knowledge of anatomy facility in
      clinical evaluation of spreading malignancy. It helps in proper qualification to
      surgery or radiotherapy.

PMID- 16095089
TI  - [Acute lymphadenitis of the neck in children].
AB  - We report on 34 children with acute lymphadenitis of the neck at the age between
      10 months to 12 years who were admitted in our Department of Otolaryngology
      Children Hospital in Warsaw between 2001-2003. In a retrospective study we
      evaluated clinical features and diagnostic impact of ultrasonography, white blood
      cell count, C-reactive protein as well as bacterial etiology of children treated
      surgically for bacterial cervical lymphadenitis. Leukocytosis and elevated
      concentrations of C-reactive protein occurred in the majority of patients in 32
      children (94.12%). 24 children (70.59%) we treated conservatively. Clinical
      appearance and the result of ultrasound examination were relevant for diagnosis
      of suppurative inflammation. Treatment included antibiotic therapy in all cases
      and incision and drainage in 10 cases (29.4%). A positive culture grew in 20% of
      children treated surgically and of these isolates we found Streptococcus pyogenes
      and Streptococcus species. In these cases surgical drainage is a key to
      appropriate resolution. USG diagnoses were retrospectively correlated with
      clinical and surgical findings or with the outcome of treatment in 87.5% of
      children.

PMID- 16095090
TI  - [The use of superselective embolization of the maxillary artery in treatment of
      bleedings in the Rendu-Osler-Weber syndrome].
AB  - Rendu-Osler-Weber syndrome is a rare genetically determined disorder that affects
      blood vessels throughout the body and results in a tendency for bleeding. Authors
      describe the case of superselective embolization of the left maxillary artery
      with polyvinyl alcohol particles in a patient with the Rendu-Osler-Weber syndrome
      hospitalized and treated in the Department of Otolaryngology and the Department
      of Radiology of the Military Institute in Warszawa, Poland due to persistent,
      severe and difficult to manage nasal bleeding. After the procedure had been
      performed patient condition improved and frequency and severity of nasal bleeding
      significantly diminished. Authors conclude that superselective embolization of
      the maxillary artery in a patient with Rendu-Osler-Weber syndrome is safe and
      effective and can be a valuable alternative to the maxillary artery or the
      carotis externa artery ligation. Authors also describe other methods of nasal
      bleeding management: laser photocoagulation, argon plasma coagulation, nasal
      dermoplasty and pharmacological treatment. Authors indicate that treating
      patients with Rendu-Osler-Weber syndrome is a diagnostic and therapeutic
      challenge for a physician and surgeon that require special approach to a patient
      due to difficult to manage symptoms. Patients with Rendu-Osler-Weber syndrome
      should be treated in a hospital setting due to access to diagnostic imaging
      techniques that can be helpful in revealing possible life threatening conditions.

PMID- 16095091
TI  - [Expression of receptor CD23+ on B lymphocytes in hypertrophied adenoids of
      children with otitis media with effusion].
AB  - Tonsil pharyngeal is stimulated chronic by pathogens can be causes this
      hypertrophied; whose often is companions to otitis media with effusion.
      Subpopulation dominates in tonsil pharyngeal are lymphocytes B, and their markers
      activation are expression of antigen CD23+. The aim of this study was finding
      dependence between otitis media with effusion and coexistent hypertrophy
      adenoids, and percentage of lymphocytes CD19+ with expression of antigen CD23+ in
      hypertrophy adenoids. In the study showed higher significant percentage of
      lymphocytes CD19+ CD23+ at children in otitis media with effusion (20.08+/-2.93)
      with reference to comparative group, which was only hypertrophy adenoid (18.16+/
      2.25). Percentage lymphocytes B (CD23+) were the highest (20.01+/-5.81) in
      children subgroup above 5 years old with otitis media with effusion, and lowest
      (17.36+/-2.78) in children comparative subgroup above 5 years old. As regards on
      different functions of antigen CD23+ the assessment of percentage lymphocytes B
      with expression of CD23+ can be additional marker in course immunological and
      inflammatory processes to occur in hypertrophy adenoids at children are sick
      otitis media with effusion.

PMID- 16095092
TI  - [Speech rehabilitation using Provox voice prosthesis].
AB  - The first voice prosthesis was described in 1972 by Mozolewski. Eight years later
      Blom and Singer constructed the first commercial prosthesis. In 1988 another
      prosthesis was presented as Provox system prosthesis. The aim of the study was to
      describe the technique of tracheoesophageal puncture (TEP) and to present two
      years results of the technique performed in 21 patients. Primary TEP with
      immediate implantation of the Provox 2 prosthesis was applied in 16 (76%)
      patients. In five patients (24%) secondary TEP was performed. All the patient
      with primary TEP had cricopharyngeal myotomy. In 7 patients the vocal prosthesis
      was exchanged. In five because of leakage through the valve and in two patients
      the vocal prosthesis was extruded. Leakage around the prosthesis occurred in two
      patients with secondary TEP. The mean device-related lifetime was 216 days and
      ranged from 30 to 540 days. In non-radiated patients the lifetime of the
      prosthesis was 255 days and in patients after radiotherapy the lifetime was 150
      days. In all the patients the prosthetic voice was more similar to normal voice
      than in patients with esophageal speech. The implantation of the voice prosthesis
      is a simple method of restoring of a good quality voice enabling communication.

PMID- 16095093
TI  - [Efficacy of primary and combined radiotherapy in locally advanced cancer of
      oropharynx and nasopharynx in III and IV stage].
AB  - Aim of the study is evaluation of radiotherapy treatment in cancer of oropharynx
      and nasopharynx. Retrospective analysis was based on 283 patients in III and IV
      clinical stage of disease without distant metastases who were treated between
      1989-2001. 201 patients were treated radiotherapy alone and 82 by combined
      modality: radiotherapy and chemotherapy. Induction chemotherapy and radiotherapy
      was used in 34 cases, concomitant chemoradiotherapy--25 and adjuvant chemotherapy
      and radiotherapy in 23 cases. Following methods of radiotherapy fractionation
      were used: accelerated in 35 cases, conventional--26, hyperfractionation--21.
      Accelerated treatment mainly was used in concomitant combined modality. Log-rank
      statistical analysis revealed better results of treatment for combined modality:
      radiotherapy and chemotherapy. Most effectiveness method of combined modality was
      concomitant radiochemotherapy. Locoregional control in 3 years observation
      interval was better for concomitant mode about 18% comparing to induction
      chemotherapy and radiotherapy and 30% to adjuvant chemotherapy and radiotherapy.
      Based on this data, the optimal mode of treatment in III and IV stage of
      oropharyngeal and nasopharyngeal cancer, especially with extensive nodal disease
      and extranodal involvement is concomitant treatment with accelerated
      fractionation dose of radiotherapy.

PMID- 16095094
TI  - [Long-term results of treatment in T1, T2 laryngeal cancer with CO2 laser
      microsurgery].
AB  - The aim of this study was estimation the long term results of CO2 laser therapy
      in laryngeal cancer. 36 patients with early glottic cancer-T1 and T2 were treated
      with CO2 laser microsurgery in 1990-1992. The control laryngological, phoniatric
      and laryngovideostroboscopic examinations were conducted from six to thirty
      months after the operation. The next controls were done within three years and
      then after eight to ten years from microsurgery. The local recurrence was
      observed only during the first control in seven cases--19%. Four patients
      underwent total laryngectomy after several laser microsurgery, two were treated
      only with CO2 laser and one had CO-therapy. The better quality of voice was
      observed during following control examinations. A scar with smooth surface and
      marge in 29 persons and a tendency to phonatory vibration of scar in 9 patients
      were noticed in laryngovideostroboscopy examination during the first control.
      Following examinations showed a progressive improvement of voice parameters.

PMID- 16095095
TI  - [Prophylaxis of venous thromboembolism in otolaryngology--head and neck surgery].
AB  - Venous thromboembolic disease (deep vein thrombosis and pulmonary embolism) is a
      frequent and dangerous complication of surgical procedures. Guidelines
      considering prophylaxis in patients who have a risk of this complication exist in
      most surgical specialties. In otolaryngology it is a rare illness but a lack of
      Polish literature and quite few world publications on this subject made the
      authors check through the literature referring to venous thromboembolic disease
      in otolaryngology and maxillofacial surgery and indexed in the EMBASE and MEDLINE
      data bases up till 2003. Incidence of the disease, risk factors with regard to
      the kind of surgery and prophylaxis methods were presented, all with the aim of
      creating a kind of a guide useful in clinical practice in ENT.

PMID- 16095096
TI  - [Early results of the treatment of chronic sinusitis with functional endoscopic
      sinus surgery].
AB  - In recent years FESS has become a gold standard in the treatment of chronic
      sinusitis. The results of the treatment depends to a high degree on the thorough
      preoperative assessment and qualification for surgery, as well as applied
      criteria reported for success. The aim of the study was to evaluate the early
      results of FESS in patient with chronic sinusitis after 3 to 12 month of follow
      up focusing attention on some prognostic factors. In the group 52 patients who
      underwent FESS in 2003 due to chronic sinusitis particular attention to
      standardization of pre and postoperative evaluation was paid. Meticulous analysis
      of the data from SNAQ 11 (sino nasal assessment questionnaire) questionnaire for
      subjective complaints evaluation, and assessment of the extent of disease
      according to Friedman, Kennedy and Levine scale revealed no correlation between
      extent of disease and results of treatment. It was demonstrated, that there is
      the statistically significant correlation between extent of sinus disease on CT
      scans and the duration of disease. It applies to the first tree years of disease.

PMID- 16095097
TI  - [Malignant neoplasms of external and middle ear].
AB  - INTRODUCTION: Neoplasms of external and middle ear are rare, which cause several
      problems in diagnosis and therapy. The purpose of the study was to analyze
      retrospectively patients with malignant neoplasms of the ear. METHODOLOGY: The
      study was carried out on 53 patients treated for malignant ear neoplasms in
      single institution during 25 years (1978-2002). RESULTS: The most frequent
      neoplasm was squamous cell carcinoma--36 cases (67.9%), then basal cell carcinoma
      -9 cases (16.9%). Neoplasm primarily involved auricle in 26 patients (49.1%),
      external auditory canal in 15 patients (28.3%) and middle ear in 12 patients
      (22.6%). They were classified according to Stell and McCormick (1985) as follows:
      stage I--29 tumours (54.7%), stage T2--15 tumours (28.3%), stage T3--9 tumours
      (17%). Facial nerve paresis occurred in 15 patients (28.3%). The most often
      treatment modality was surgery--32 persons (60.4%), then surgery followed by
      radiotherapy--17 persons (32.1%). The characteristics of neoplasms related to the
      site of location were described. The difficulties in precise histopathologic
      diagnosis and extent of disease were pointed out. RESULTS: Neoplasms of external
      and middle ear constitute a group of various histopathological and clinical
      tumours, which differ in diagnostic difficulties, treatment and prognosis. A
      diagnosis was often made in advanced stages of neoplasms, especially for middle
      ear tumours, that diminished a possibility of effective treatment.

PMID- 16095098
TI  - [Effect of the middle ear status on the recording of vestibular evoked myogenic
      potential--VEMP].
AB  - The aim of this study was to assess the effect of the middle ear status on the
      recording of air- and bone-conducted vestibular evoked myogenic potential. Forty
      eight children were included in the study, ranging in age from 4 to 10 years. All
      of the children underwent otoscopy, pure tone audiometry, tympanometry and air-
      and bone-conducted VEMP in response to click. There were 3 groups according to
      the condition of the middle ear: group I--52 ears (type A and C1 tympanogram,
      pure tone average < or = 20 dB), group II--23 ears (type C2 and B tympanogram,
      pure tone average < or = 20 dB), group III--21 (type B tympanogram, pure tone
      average > 20 dB). The threshold, presence of correct waveform morphology of the
      response and latency was evaluated. The condition of the middle ear has no
      significant effect on the recording of VEMP and mean level of the response
      threshold with bone stimulation, based on the performed studies. However, with
      air stimulation it has effect on the recording of VEMP, increase of the mean
      threshold response and shortening of latency p13 and n23.

PMID- 16095099
TI  - [Results of stapedotomy in the cases of "floating footplate"].
AB  - One of the problems in the stapes surgery is the floating footplate. The
      frequency of incidence of this complication is 2% to 5.8% of all operations. The
      authors present the results of stapes operations in a group of 28 cases (2.5%)
      from all the 1120 operations, in which the surgeon experienced a floating
      footplate. The hearing results were evaluated on the base of the average gain of
      air-conduction thresholds and air-bone gap levels at 500, 1000, 2000 and 3000 Hz.
      The improvement of hearing we observed in 24 patients, 4 patients heard worse.

PMID- 16095100
TI  - [Application of conscious sedation in infants undergoing the auditory brainstem
      responses (ABR) examination].
AB  - Results of ABR examination in infants undergone the hearing screening
      examinations were presented. Since February 2004 the group of 184 children were
      examined. In 29 of them (15.8%) there was a need of further hearing examination
      using evoked auditory brainstem responses. In 20 of them the examination was done
      in sleep induced by 6% chloral hydrate enema. The process of sleep was normal and
      no disturbances of breathing or circulatory systems were observed. The obtained
      responses from brainstem were not interfered by any artifacts and basic waves
      were legible and easy for interpretation. Correct results of the ABR examination
      were obtained in 21/29 (72%) children, while in 7/28 (24%) various degree of
      hearing losses were detected. Those children were referred for hearing
      rehabilitation to the Third Degree of Reference Center. It was emphasized in the
      study that results of ABR examination after conscious sedation induced by 6%
      chloral hydrate enema accounted the suggestion for its wider use in other
      clinical and hospital center.

PMID- 16095101
TI  - [Impact of tinnitus on quality of life in the patients' self-assessment].
AB  - Tinnitus may have multidirectional impact on patients and influence unfavourably
      their quality of life and psychology. The aim of the study was to investigate the
      aetiology, audiological parameters, and tinnitus characteristics and to evaluate
      the impact of tinnitus on patients life and emotional status by using the self
      report questionnaire. A group of 157 consecutive patients referred to the Otiatry
      Clinic Medical University in Lodz were enrolled in the study. It was found that
      tinnitus negatively impact on 2/3 of patients and 1/3 of them consider it as
      annoying. The most frequent aetiological factor was noise exposure (40.8%). There
      was no correlation between tinnitus loudness and degree of hearing loss on the
      one hand and self-perceived handicap and annoyance of tinnitus on the other. It
      was stated that younger age and higher tinnitus pitch-match frequencies may
      influence patients' quality of life.

PMID- 16095102
TI  - [Alcaligenes xylosoxidans--a pathogen of chronic ear infection].
AB  - INTRODUCTION: We discuss a case of a 48-year old man admitted to our Department
      with symptoms of chronic ear infection, that didn't answer to typical
      conservative treatment. The culture of the discharge was positive for Alcaligenes
      xylosoxidans. MATERIAL AND METHODS: We report characteristic features of that
      bacteria and we compare them with features of other pathogens typical for otitis
      media. We present performed treatment too. RESULTS: Alcaligenes xylosoxidans is a
      nonfermenting gram-negative rod. It can be confused with other nonfermentive,
      gram-negative rods, especially Pseudomonas species, in clinical specimens so that
      its role as a significant pathogen may be underestimated. Alcaligenes
      xylosoxidans is a part of normal human flora, especially skin and
      gastrointestinal tract, and can cause serious infections in human (especially in
      patients with immunodeficiency and premature children). CONCLUSIONS: Reports
      about Alcaligenes xylosoxidans as a cause of chronic otitis media are very rare
      and it can be supposed to stay a new kind of ear infection.

PMID- 16095103
TI  - [Unusual case of the long term presence of esophageal foreign body (non
      radiopaque coin) in children].
AB  - The authors report an unusual case of a foreign body in the esophagus of a child
      present for longer than 2 years. As an infant this child had repair of esophageal
      atresia. She was examined and assessed 2 years ago for suspected foreign body
      swallowing. Chest and abdominal xrays did not show the presence of any foreign
      body. Now this child was re-admitted with a foreign body in the esophagus, a
      piece of meat. X rays showed narrowing at previous anastomosis site and
      dilatation proximally. At esophagoscopy after removal of the piece of meat, a
      coin was removed as well (50 Hungarian fills). This coin has low radiopacity so
      did not contrast well in soft tissue. It is worth pointing out that despite
      having a foreign body this child did not have any difficulty with swallowing and
      development was normal.

PMID- 16095104
TI  - [Osteosarcoma of the larynx].
AB  - The authors present a case of rare laryngeal neoplasm--osteosarcoma, which
      generated many diagnostic and treatment difficulties. Its main cause was
      nonspecific symptoms and laryngoscopic view, positive tuberculous history and
      positive tuberculosis tests. The first histopathological examination was
      "angioleiomyoma exulcerans, chronic inflammation and granulation." No cancer nor
      tuberculosis was found". After the physiologic consultations and with positive
      tuberculin test the tuberculocidal treatment was applied, but it bought no
      success. The larynx was split then, intraoperative histopathological examination
      gave the result: "Cellulae carcinomatosae". The total laryngectomy was performed.
      Postoperative immunohistochemical examination was "Osteosarcoma of larynx". The
      patient was not evaluated for radio- or chemotherapy. Admitted to the hospital
      after 5 months with neck tumor and reactional lymph nodes by the right side of
      the neck. Crile's operation was performed. During the postoperative course some
      metastatic lymph nodes on the left side of the neck and in lungs were detected.
      Patient noted to chemotherapy.

PMID- 16095105
TI  - [The usefulness of computer-aided navigation in endoscopic sinus and nasal
      surgery].
AB  - The usefulness of computer-aided navigation in endoscopic sinus and nasal
      surgery. Endoscopic surgeries of the sinuses are among the most difficult
      procedures in otolaryngology. The progress of endoscopic techniques led to
      reduction of invasiveness enabling the surgeon to perform precise procedures with
      minimal tissue traumatization. The systems for computer-aided endoscopic surgery
      combine preprocedural MRI or CT data with information regarding current location
      of the surgical tools. The aim of this study was to assess the usefulness of
      electromagnetic navigation system ENTrak 3500 in endoscopic nasal and sinus
      surgery. The study group consisted of 18 consecutive patients with maxillary or
      ethmoid sinusitis with concomitant nasal polyps, who were surgically treated in
      ENT Clinic Military Medical Institute in October 2003. In all patients the
      endoscopic nasal and sinus surgery with the use of computer-aided navigation was
      successful with complete removal of pathologic lesions within the cavities of the
      nose, maxillary and/or ethmoid sinuses.

PMID- 16095106
TI  - [Some thoughts on hearing aids--good choice and and proper fitting A-Life 9000
      system sponsored by Geers (program geers.net)].

PMID- 16095107
TI  - [40th anniversary of the establishment of the Otolaryngologic Department at the
      Military Medical University in Warsaw].

PMID- 16095108
TI  - [Report from Polish Otolaryngologic Society conference].

PMID- 16095109
TI  - Antifolate/antiproliferative therapy in rheumatoid arthritis.

PMID- 16095110
TI  - Inhibition of glycinamide ribonucleotide formyltransferase results in selective
      inhibition of macrophage cytokine secretion in vitro and in vivo efficacy in rat
      adjuvant arthritis.
AB  - OBJECTIVE: To determine the effects of a glycinamide ribonucleotide
      formyltransferase (GARFT) inhibitor on macrophage inflammatory processes and in
      vivo in rat adjuvant arthritis. METHODS: GARFT inhibitors, LY309886 (6S-2',5'
      thienyl-5, 10-dideazatetrahydrofolic acid) and LY329201 (R)-N-[[5-[2-(2-amino
      1,4,5,6,7,8-hexahydro-4-oxopyrido[2,3-d]pyrimidin-6-yl)ethyl]-2-thienyl]carbonyl]
      L-glutamatic acid disodium salt, were investigated in vitro and ex vivo on
      primary murine peritoneal macrophages and in the RAW macrophage cell line for
      both purine depletion and inhibition of LPS induced monokine secretion. In vivo
      efficacy following GARFT inhibition was evaluated in modified rat adjuvant
      arthritis. RESULTS: LY309886 inhibited purine biosynthesis in the RAW cell line
      with an EC50 of 90 nM, an effect readily reversible with exogenous hypoxanthine.
      LY309886 and LY329201 also inhibited LPS induced TNF alpha and MIP1 alpha in
      these cells and in primary macrophages. A similar effect could be demonstrated ex
      vivo with mice dosed for two days with 3 mg/kg of LY329201. LY329201 as well as
      methotrexate demonstrated a dose dependent reduction in both paw and spleen
      weight and improved joint histology following 2 weeks of dosing in a rat adjuvant
      arthritis study. CONCLUSION: These results suggest that GARFT inhibitors should
      be tested in the treatment of rheumatoid arthritis by considering their mechanism
      of action, here successfully tested on activated macrophages.

PMID- 16095111
TI  - Prevalence of pulmonary hypertension in systemic sclerosis.
AB  - OBJECTIVE: To assess the prevalence of pulmonary arterial hypertension (PAH) in
      patients with the diagnosis of systemic sclerosis (SSc) followed at a tertiary
      university service. MATERIAL AND METHODS: Fifty-seven patients with SSc were
      studied by clinical assessment directed at the cardiopulmonary system, pulmonary
      function tests and Doppler echocardiography (ECHO). The following criteria were
      considered for the diagnosis of PAH: pulmonary artery systolic pressure (PASP) >
      or = 40 mmHg and/or the presence of other direct and indirect signs of PAH
      detected upon ECHO. RESULTS: Sixteen patients (28%) were diagnosed with PAH upon
      ECHO, 13 based on PASP > or = 40 mmHg and 3 based on direct and indirect signs of
      PAH; 8 patients had isolated PAH and 8 had PAH secondary to pulmonary fibrosis.
      Nine patients showed signs suggestive of cor pulmonale upon ECHO; among these
      patients, 6 had pressure recordings > or = 40 mmHg and 3 had a PSAP between 35
      and 40 mmHg; one patient was asymptomatic and 8 showed signs suggestive of PAH
      upon clinical examination. Among the clinical and laboratory variables studied, a
      correlation was only observed between PAH and an elevated erythrocyte
      sedimentation rate (p = 0.004). CONCLUSIONS: The prevalence of PAH associated
      with SSc observed in this study was similar to those reported in the literature.
      However, the cut-off of PSAP measured by ECHO and used for the diagnosis of PAH
      associated with SSc needs to be revised.

PMID- 16095112
TI  - Adeno-associated virus vector-mediated anti-angiogenic gene therapy for collagen
      induced arthritis in mice.
AB  - OBJECTIVE: The goal of this study was to determine the utility of adeno
      associated virus (AAV) vectors for anti-angiogenic gene therapy in a mouse model
      of collagen-induced arthritis (CIA). METHODS: CIA mice were generated by
      immunization with bovine type-II collagen and Freund's complete adjuvant. AAV
      vectors containing angiostatin and enhanced green fluorescent protein (eGFP)
      expression units (AAV-Ang/GFP) or the GFP and neomycin phosphotransferase (NeoR)
      expression units (AAV-GFP/NeoR) were injected into mouse knee joints before
      development of arthritis. The expression of transgenes was confirmed by reverse
      transcriptase polymerase chain reaction (RT-PCR) and immunostaining, and the
      incidence and severity of arthritis was determined histologically via assessment
      of synovial hyperplasia, cartilage erosion and bone erosion. Vascularity in the
      knee joint was evaluated by immunohistochemical staining with anti-von Willebrand
      factor antibody. RESULTS: AAV vectors were capable of efficient gene transfer
      into chondrocytes and synovial cells, and the extent of synovial hyperplasia and
      other parameters of arthritis were significantly reduced in the knee joints
      injected with AAV-Ang/GFP compared with the joints treated with either AAV
      GFP/NeoR or phosphate-buffered solution (PBS). Reduction in the number of vessels
      was confirmed in AAV-Ang/GFP-treated joints. CONCLUSION: AAV-vector-mediated
      local expression of angiostatin efficiently inhibited the development of collagen
      induced arthritis in the treated joint. Anti-angiogenic gene therapy using AAV
      vector may provide a new approach for the effective treatment of rheumatoid
      arthritis.

PMID- 16095113
TI  - Inflammatory changes of hip synovial structures in polymyalgia rheumatica.
AB  - OBJECTIVE: To investigate the hip inflammatory lesions and to evaluate the
      accuracy of clinical examination compared to magnetic resonance imaging (MRI) in
      patients with polymyalgia rheumatica (PMR) with pelvic girdle symptoms. Secondary
      end-point was to evaluate the sensitivity and specificity of ultrasonography (US)
      compared to MRI in the assessment of hip lesions. METHODS: Case-control study of
      20 consecutive PMR patients and 40 controls with different rheumatic conditions.
      Both groups were clinically assessed for the presence of hip synovitis,
      trochanteric, iliopsoas and ischiogluteal bursitis. Hip MRI was performed in all
      case-patients and in 10 controls. Both groups were examined by US. An additional
      group of 10 healthy controls was examined by hip US. RESULTS: Both MRI and US
      detected trochanteric bursitis in 100% of PMR patients, bilateral in 18/20 (90%),
      and in 12/40 (30%) controls (p < 0.001). Hip synovitis was detected in 17/20
      (85%) by MRI and in 9/20 (45%) by US (p < 0.02) in case-patients and in 18/40
      (45%) controls. In PMR, MRI and US showed iliopsoas bursitis in 10/20 (50%) and
      6/20 (30%) and ischiogluteal bursitis in 5/20 (25%) and 4/20 (20%) with no
      differences compared to controls. Clinical examination showed a good accuracy for
      hip synovitis, trochanteric and ischiogluteal bursitis, while it overestimated
      the presence of iliopsoas bursitis. US was less sensitive than MRI for the
      detection of hip synovitis and iliopsoas bursitis (53% and 60%). CONCLUSION:
      Trochanteric bursitis represents the most frequent hip lesion in PMR. A careful
      physical examination allows to detect all inflammatory lesions excluding
      iliopsoas bursitis. US is less sensitive than MRI in the assessment of hip
      synovitis and iliopsoas bursitis.

PMID- 16095114
TI  - Anti-tumor necrosis factor (TNF) therapy in rheumatoid arthritis: correlation of
      TNF-alpha serum level with clinical response and benefit from changing dose or
      frequency of infliximab infusions.
AB  - OBJECTIVE: To determine the relationship between serum TNF-alpha level and
      clinical response in rheumatoid arthritis patients treated by infliximab. This
      could be of value to predict clinical response to infliximab and to determine the
      optimal dose and interval between dosing of infliximab. RA patients who did not
      respond adequately to conventional doses (3 mg/kg) of infliximab were studied to
      see if increasing the dose or frequency of infliximab infusions would be more
      effective. METHODS: Fifty-five RA patients who fulfilled the American College of
      Rheumatology criteria and were receiving treatment by anti-TNF-alpha (infliximab
      3 mg/kg body weight every 8 weeks) were evaluated by: clinical disease activity
      using the Richie score index before receiving their scheduled infliximab
      infusion. Serum level of TNF-alpha, as measured by competitive ELISA assay, was
      determined immediately before and 9-11 days after receiving infliximab. RA
      patients who did not respond adequately to treatment with infliximab were given
      either a larger dose of infliximab or given the infusion at six-week intervals.
      Their clinical response was then evaluated sixteen months later. RESULTS Patients
      were divided into 2 groups according to Richie score, active group with score >
      10 (score 20.3 +/- 7.7 mean +/- standard deviation, n = 25) and inactive group
      with scores < or = 10 (score 4.1 +/- 3.2, n = 30). TNF-alpha serum levels pre
      infliximab infusion were significantly higher in the active group 76.1 pg/ml than
      the inactive group 38.0 pg/ml (P < 0.02). Whereas TNF serum level significantly
      dropped post infliximab in the inactive group (P < 0.05), it did not drop in the
      active group. The mean level of the post-infusion TNF-alpha serum level was
      higher (76.6 +/- 93.4 ng/ml) in the-active than the mean level of the post
      infusion serum TNF-alpha levels in the inactive group (26.4 ng/ml +/- 7.9) P <
      0.01 using the t-test. Increasing the frequency was superior in RA patients'
      clinical outcome than increasing the dose of infliximab infusions. CONCLUSION: RA
      patients who responded well to infliximab and had inactive disease at the time of
      the study have lower levels of serum TNF-alpha which could be further suppressed
      by the recommended doses of infliximab. RA patients with active disease have
      higher serum levels of TNF-alpha which could not be suppressed after the
      recommended doses of infliximab infusion. Changing the frequency of infliximab
      infusions in the active group was more effective than increasing the dose of
      infliximab in inducing improved clinical outcome. We suggest that the lack of
      suppression of TNF-alpha in the active group could be due to inadequate dosing of
      infliximab or to the presence of a neutralizing antibody directed against
      infliximab. It remains to be seen if serum TNF-alpha levels could be used as a
      guide in determining the dose and intervals between dosing of anti-TNF therapy in
      RA in order to achieve the desired clinical response.

PMID- 16095115
TI  - A retrospective study of the fluctuation in serum levels of anti-cyclic
      citrullinated peptide antibody in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the fluctuation in serum levels of anti-cyclic
      citrullinated peptide antibody (anti-CCP) retrospectively in patients with
      rheumatoid arthritis (RA). METHODS: Serum levels of anti-CCP were measured
      retrospectively in 131 patients with RA and 90 patients with non-RA rheumatic
      diseases using a commercially available kit. All sera were collected from
      patients during the 22-year period, 1982-2004. To analyze the fluctuation in anti
      CCP levels, 17 RA patients were selected on the basis of showing a significantly
      higher anti-CCP level in a serum sample taken at the first visit (> 80 U/ml), and
      availability of preserved serum samples that had been taken from each patient at
      10 time points. RESULTS: The test gave a sensitivity of 88% (115/131) and a
      specificity of 81% (73/90). The longitudinal study of 17 RA patients showed that
      anti-CCP levels were elevated at the first visit in 12 (71%) patients and then
      decreased gradually, whereas those in the other five (29%) patients fluctuated
      substantially. In both cases, anti-CCP levels tended to fluctuate in parallel
      with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level,
      reflecting the spontaneous aggravation of arthritis and the efficacy of anti
      rheumatic drugs. The courses of three representative RA patients are illustrated
      in detail along with their therapeutic regimens, and these further confirm the
      correlation of anti-CCP levels with laboratory parameters (ESR and CRP) as well
      as the activity of arthritis. CONCLUSION: Measurement of serum anti-CCP levels
      was found to be useful for not only the diagnosis but also the management of RA.

PMID- 16095116
TI  - Autoantibodies against oxidized low-density lipoprotein (LDL) and carotid
      atherosclerosis in patients with rheumatoid arthritis.
AB  - OBJECTIVES: To examine the relationship between autoantibodies against oxidized
      low-density lipoprotein (oxLDL-Abs) and the progression of carotid
      atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: Fifty RA
      patients without evidence of risk factors for atherosclerosis (RA group) and 30
      healthy volunteers (normal group) were investigated. The mean intima-media
      thickness of the common carotid artery (mean CCA-IMT) was measured by high
      resolution B-mode ultrasonography. The titer of IgG oxLDL-Abs was measured by
      enzyme-linked immunosorbent assay. The relationships among mean CCA-IMT, IgG
      oxLDL-Ab titer and patient factors such as body mass index, systolic blood
      pressure, diastolic blood pressure, C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), and serum lipid levels were examined. RESULTS: Mean CCA
      IMT, CRP, ESR and titer of IgG oxLDL-Abs were significantly higher in the RA
      group than in the normal group. Although mean CCA-IMT showed a positive
      correlation only with age in multivariate analysis, IgG oxLDL-Ab titers in the RA
      group were positively associated with mean CCA-IMT and independently with age and
      sex by multiple regression analysis. CONCLUSIONS: IgG oxLDL-Abs appear to be
      associated with the degree of carotid atherosclerosis in patients with RA, and
      are independent of traditional risk factors for atherosclerotic diseases. These
      results suggest a possible link between autoimmune mechanisms and accelerated
      atherosclerosis in RA.

PMID- 16095117
TI  - Vascular endothelial growth factor activities on osteoarthritic chondrocytes.
AB  - OBJECTIVE: Evaluation of the role of VEGF in cartilage pathophysiology. METHODS:
      VEGF release from chondrocytes in the presence of IL-1beta, TGFbeta and IL-10 was
      detected by immunoassay. VEGF receptor -1 and -2 expression and VEGF ability to
      modulate caspase -3 and cathepsin B expression were detected by
      immunohistochemistry on cartilage biopsies and cartilage explants. VEGF effects
      on chondrocyte proliferation was analysed by a fluorescent dye that binds nucleic
      acids. RESULTS: VEGF production by osteoartritis (OA) chondrocytes was
      significantly reduced by IL-1beta while it was increased in the presence of
      TGFbeta. Cartilage VEGFR-1 immunostaining was significantly downregulated in
      'early' OA patients compared to normal controls (NC). VEGFR-2 expression was
      negligible both in OA and in NC. VEGF decreased the expression of caspase-3 and
      cathepsin B, whereas it did not affect proliferation. CONCLUSION: VEGF is able to
      down-modulate chondrocyte activities related to catabolic events involved in OA
      cartilage degradation.

PMID- 16095118
TI  - The genetic contribution of the TNFa11 microsatellite allele and the TNFb + 252*2
      allele in Japanese RA.
AB  - OBJECTIVES: The contribution of the microsatellite polymorphisms of TNFa and
      TNFb, and the TNFB + 252 (TNFB) dimorphism to the pathogenesis of rheumatoid
      arthritis (RA) was studied among Japanese patients. METHODS: The TNFa and TNFb
      microsatellite polymorphisms, and the TNFB dimorphism were determined in Japanese
      RA patients and normal subjects using electrophoresis followed by specific PCR
      amplification. HLA-DRB1*04 typing was carried out by the PCR-SSCP method.
      RESULTS: The allele frequency of TNFa11 showed a significant increase in RA with
      DRB1*0405 when compared to that in RA without DRB1*0405 (28.5% Vs 12.9%,
      respectively, p = 0.022). An association analysis indicated that TNFa11 was not
      primary, but secondary to the increase in HLA-DRB1*0405, because TNFa11 showed a
      strong positive association with HLA-DRB1*0405 in Japanese controls. The slight
      increase in the TNFb4 allele observed in RA with DRB1*0405 (50.0%) may be
      reflective of the increase in TNFa11 and DRB1*0405. In RA with DRB1*0405, the
      allele frequency of TNFB*2 significantly increased compared to that of normal
      controls (75.0% Vs 55.3%, respectively, p = 0.007) and compared to that of RA
      without DRB1*0405 (45.0%, p = 0.001). No significant positive association of
      TNFB*2 with HLA-DRB1*0405 or TNFa11 in Japanese controls might suggest that the
      increase in the TNFB*2 allele might not be secondary to the increase in
      DRB1*0405, and that TNFB*2 might contribute additively to DRB1*0405-positive RA
      in Japanese. CONCLUSION: TNFB*2 may contribute additively to Japanese RA with HLA
      DRB1*0405, while TNFa11 and TNFb4 are not independent genetic markers of RA among
      Japanese.

PMID- 16095119
TI  - Livedo reticularis is a marker for predicting multi-system thrombosis in
      antiphospholipid syndrome.
AB  - OBJECTIVE: Livedo reticularis (LR) is a skin vasculopathy that has been
      frequently described in patients with anti-phospholipid syndrome (APS) and
      reported to be present in association with valvular heart pathology and strokes
      (i.e. Sneddon's syndrome). METHODS: In a cohort of APS patients we investigated
      the possible association of LR with various clinical aspects of APS such as
      pregnancy morbidity, central nervous system (CNS) and cardiac manifestations.
      RESULTS: Livedo reticularis was found in 50/308 (16%) of APS patients, and there
      was a significant association with cerebrovascular accidents (CVA), migraines and
      epilepsy (p = 0.01, 0.002, and 0.02 respectively). A similar association was also
      detected between LR, and the presence of cardiac valve thickening and vegetations
      (p = 0.001). No association with venous thrombosis, recurrent fetal loss, IUGR or
      toxemia was found. CONCLUSION: Livedo reticularis is a frequent cutaneous
      manifestation in patients with APS. Its high association with cardiac and CNS
      thrombosis may suggest that LR-APS patients compose a subset at higher risk for
      thrombosis, and thus may require a closer follow-up and a more aggressive
      anticoagulation.

PMID- 16095120
TI  - Effects of prolonged combined strength and endurance training on physical
      fitness, body composition and serum hormones in women with rheumatoid arthritis
      and in healthy controls.
AB  - OBJECTIVE: The effects of a 21-week combined strength and endurance training
      period on physical fitness, serum hormone concentrations, and subcutaneous fat in
      23 women with rheumatoid arthritis (RA) and in 12 matched healthy subjects was
      studied. METHODS: The measurements included leg extension forces and EMG
      activity, muscle and fat thickness on thigh, maximal oxygen uptake (VO2max) and
      serum concentrations of testosterone, free testosterone, growth hormone, insulin
      like growth factor-I (IGF-I), dehydroepiandrosterone sulphate (DHEAS), and
      cortisol. RESULTS: During the training period significant increases took place in
      VO2max, muscle strength and EMG activity in both groups. The increases of the
      quadriceps femoris thickness were 6.5% (p < 0.001) in the healthy controls and
      7.4% (p < 0.001) in the RA cases. The decreases in subcutaneous fat thicknesses
      were 9.9% (p < 0.001) and 12.3% (p < 0.001), respectively. No significant changes
      were found in serum hormone concentrations, but RA women showed lower levels of
      IGF-I during the whole follow-up. CONCLUSIONS: In RA women with stable disease
      the combined strength and endurance training increases physical fitness. Further
      the training increases muscle mass and decreases subcutaneous fat. It may
      decrease risks of cardiovascular diseases in RA patients. The intensive training
      had minor effects on serum hormone concentrations.

PMID- 16095121
TI  - Low dose of infliximab is inadequate in most patients with spondylarthropathies.
AB  - OBJECTIVES: The recommended starting dose for infliximab for ankylosing
      spondylitis 5mg/kg is higher than that for rheumatoid arthritis. Because of the
      high expense of the drug lower doses may be considered. We report our experience
      with lower initial doses. METHODS: Thirty patients with active SpA (16 psoriatic
      arthritis, 12 ankylosing spondylitis and 2 undifferentiated) received 6
      infliximab infusions. Patients had substantial axial disease (mean BASDAI at
      baseline 5.5). Concomitant therapy (methotrexate or prednisolone) remained stable
      throughout treatment period. The mean initial dose of infliximab was 3.5
      mg/kg/infusion. Clinical efficacy was assessed by BASDAI. The criterion for dose
      adjustment was a BASDAI improvement of less than 50%. The primary end-points were
      the proportion of patients requiring a dose adjustment and the percentage of
      patients achieving 50% improvement in BASDAI after 6 infusions. RESULTS: In this
      cohort, 2 patients discontinued therapy, 1 for pulmonary infection and 1 for
      allergic reaction. Twelve patients (40%) showed 50% improvement in BASDAI between
      baseline and prior to the 7th infusion, while 15 patients (50%) had an
      improvement > 2 points. To achieve clinical response the frequency and/or the
      dose of infliximab infusions were increased in 63% of patients. The mean
      infliximab dose increased from 3.5 mg/kg at the first infusion to 4.3 mg/kg (p <
      0.001) at the 7th infusion, resulting in a cumulative dose at the end of the
      study period comparable to the recommended one. CONCLUSIONS: In the majority of
      our SpA patients low starting doses of infliximab required subsequent adjustment.
      In these patients infliximab should be administered at the recommended dose of
      5mg/kg/infusion.

PMID- 16095122
TI  - Methotrexate use in rheumatoid arthritis is associated with few clinically
      significant liver function test abnormalities.
AB  - OBJECTIVE: To determine the frequency of liver function tests (LFT) abnormalities
      associated with methotrexate (MTX) use in the treatment of rheumatoid arthritis
      (RA). METHODS: A retrospective chart review for demographic information, RA
      specific history, medication history, complications of therapy, results of all
      available blood tests (specifically aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), complete blood count (CBC), albumin, creatinine), and
      liver biopsy reports was conducted for RA patients, who were currently using or
      have used MTX in the past. RESULTS: A total of 2791 LFTs were performed among 182
      RA patients with 94 abnormal results. 152 patients (83.5%) with 2007 LFT
      evaluations demonstrated no abnormal results, compared with 30 patients (16.5%)
      who had at least one abnormal LFT in 784 tests. Twenty-two of the 30 patients
      with at least one LFT abnormality (73.3%) continued treatment despite the
      elevation without further evaluation or change in therapy, and subsequent LFT
      assessments were within normal limits. 128 patients (70.3%) remained on MTX at
      the time of our study. The most common reason for discontinuation was inadequate
      response. CONCLUSIONS: MTX appears to be associated with very few clinically
      significant hepatic side effects. In view of these data, consideration as to
      revision of the current MTX monitoring guidelines in the direction of less
      frequent monitoring, especially in patients with no risk factors for liver
      disease, may be considered.

PMID- 16095123
TI  - A novel polymorphism of the SSA1 gene is associated with anti-SS-A/Ro52
      autoantibody in Japanese patients with primary Sjogren's syndrome.
AB  - OBJECTIVE: To investigate the association of polymorphisms of the SSA1 gene (OMIM
      109092) with primary Sjogren's syndrome (SS) and anti-SS-A/Ro52 antibody
      production. METHODS: Polymorphisms of SSA1 gene in 111 Japanese SS patients and
      in 97 healthy controls were analyzed with polymerase chain reaction and automated
      DNA sequencing. RESULTS: A new single-nucleotide polymorphism (SNP) was
      identified in intron 1 at position 7216. The allele frequency and genotype of
      7216A/G were not significantly different between SS patients and control
      subjects. However, the allele frequency and genotype of 7216A/G were associated
      with the presence of anti-SS-A/Ro52 antibody among primary SS patients. The
      association was not found in patients with SLE, suggesting the limited role for
      the SNP in anti-SS-A/Ro52 antibody production. The 9571C/T polymorphism, which
      has been shown to associate with anti-SS-A/Ro52 antibody in Caucasian patients,
      was not associated with the presence of anti-SS-A/Ro52 antibody in Japanese
      patients. CONCLUSIONS: 7216A/G polymorphism of SSA1 gene may be one of the
      genetic factors that determine the presence of anti-SS-A/Ro52 antibody in
      patients with primary SS.

PMID- 16095124
TI  - Discordance between anti-beta2-glycoprotein-I and anti-cardiolipin antibodies in
      patients with clinical criteria of antiphospholipid syndrome.
AB  - OBJECTIVES: Clinical and immunological features of patients with clinical
      manifestations of the antiphospholipid syndrome (APS) with anti-beta2
      glycoprotein-I antibodies (anti-beta2-GP-I) but without anticardiolipin
      antibodies (aCL) or any other autoimmune condition are not well documented. We
      sought to determine the clinical significance of positive anti-beta2-GP-I with
      negative aCL. METHODS: From July 2002 through July 2003, 1,179 serum samples
      obtained in our hospital from the Community of Madrid were tested for anti-beta2
      GP-I and aCL by enzyme-linked immunosorbent assay. Clinical records of patients
      with discordant anti-beta2-GP-I and aCL were retrospectively analysed. RESULTS: A
      total of 56 patients with discordant anti-beta2-GP-I and aCL were identified. By
      logistic regression analysis, after adjusting for age, sex and risk factors of
      thrombosis, the risk for developing APS criteria associated with anti-beta2-GP-I
      was significant [odds ratio 3.88; 95% confidence interval (CI): 1.05-14.27; p =
      0.04). 15 out of 56 patients (26.8%) had positive anti-beta2-GP-I and negative
      aCL. 5 out of 15 anti-beta2-GP-I-positive patients had clinical APS without
      serological nor clinical evidence of any autoimmune disease. CONCLUSION:
      Determination of anti-beta2-GP-I should be considered in individual cases with
      clinical manifestations of primary APS and repeated negative results on
      conventional antiphospholipid antibody test.

PMID- 16095125
TI  - Lack of effect of rapamycin in anti-CCP antibody production in a rheumatoid
      arthritis kidney allograft recipient.
AB  - Autoimmune diseases may lead to end-stage renal disease and, as a consequence,
      kidney transplantation. Classical immunosuppressive drugs, such as cyclosporine
      or corticosteroids, are well-established therapies for both transplantation and
      autoimmune diseases. Rapamycin is a new immunosuppressant useful for allograft
      transplantation and with a promising future for autoimmune diseases, although it
      has not been extensively studied in humans. Here the case of a patient diagnosed
      with rheumatoid arthritis (RA) who received a renal allograft is reported. She
      was started on prednisolone, azathioprine and cyclosporine immunosuppression and
      changed to rapamycin instead of cyclosporine 4 years after transplantation,
      because of chronic allograft nephropathy. At present, the patient has a
      functioning graft. However, the arthritis symptoms reappeared after the change in
      immunosuppressant. Titers of RA-specific anti-cyclic citrullinated peptides
      antibodies increased whereas rheumatoid factor titers decreased. This case report
      suggests that rapamycin used for kidney transplantation might have a different
      influence on the spectrum of RA autoantibodies.

PMID- 16095126
TI  - Behcet's disease: treatment of mucocutaneous lesions.
AB  - Oral and genital ulcers, and cutaneous vasculitic lesions are considered
      hallmarks of the disease, and often precede other manifestations. Mucocutaneous
      lesions figure prominently in the presentation and diagnosis. Therefore, their
      recognition may permit earlier diagnosis and treatment, with beneficial results
      for prognosis. This review overviews the current state of knowledge regarding the
      therapeutic approaches including local and systemic agents for the treatment of
      mucocutaneous lesions of BD.

PMID- 16095127
TI  - Usefulness of magnetic resonance sialography in patients with juvenile Sjogren's
      syndrome.
AB  - OBJECTIVE: Sialography is an important means for evaluating parotid gland damage
      in patients with Sjogren's syndrome (SS). However, 'conventional' X-ray
      sialography is invasive and sometimes difficult to perform and repeat, especially
      for young patients. Recently, magnetic resonance (MR) sialography has been used
      in adult SS patients. In this study, we investigated the usefulness of MR
      sialography for evaluating parotid gland damage in juvenile SS. METHODS: Eight
      young patients suffering from SS were studied. MR sialography and X-ray
      sialography were performed simultaneously in the same patients. The images
      obtained by both methods were assessed with Rubin-Holt staging. RESULTS: MR
      sialography detected ductal dilatation in 5 of 8 patients, while it was detected
      in 7 of 8 patients by X-ray sialography. The stages were the same in 4 patients
      by both methods. In 3 patients, the stages on X-ray sialography were higher than
      those on MR sialography; in 1 patient, the stage on MR sialography was higher.
      The correlation between the stages determined by the 2 methods was 0.85. There
      were no side effects in MR sialography, whereas 3 patients complained of pain
      during X-ray sialography. CONCLUSION: MR sialography can evaluate Stage II
      approximately III parotid gland damage in juvenile SS. Although MR sialography
      cannot detect subtle changes in the duct, it has no side effects and can be
      performed repeatedly in young patients. We propose that MR sialography be chosen
      as the first tool for diagnosing and during follow-up of the status of the glands
      in juvenile SS.

PMID- 16095128
TI  - Use of infliximab in patients with systemic juvenile idiopathic arthritis
      refractory to etanercept.
AB  - OBJECTIVE: To analyse the effectiveness and safety of Infliximab in a group of
      patients with systemic juvenile idiopathic arthritis (SJIA) who had failed
      treatment with etanercept in a single paediatric rheumatology clinic. METHODS:
      Patients with SJIA with active polyarthritis refractory to methotrexate (MTX) [>
      or = 20 mg/m2/week] for at least 3 months and to etanercept (up to 1 mg/kg twice
      weekly) for at least 6 months were included. All children received infliximab 3
      10 mg per kg of body weight intravenously concomitantly with MTX 7.5-10 mg/week
      for 19 (2-113) weeks. Evaluation included ACR paediatric 30 criteria and presence
      of signs of systemic activity (fever, rash). RESULTS: Six patients were included.
      Three patients met ACR paediatric 30 criteria at 2 weeks (2 patients) and 10
      weeks after initiation of infliximab. Improvement lasted for 4, 12, and 84 weeks
      respectively. The presence of fever/rash was not modified by the treatment.
      Infliximab was discontinued due to moderate side effects in 4 patients. No
      serious side effects were observed. CONCLUSIONS: Most patients with SJIA who fail
      to respond to etanercept may not reach sustained improvement when switched to
      infliximab. The only patient in our group who improved sustainedly with
      infliximab did not show any systemic features at the beginning of therapy.
      Further controlled studies are needed in order to assess efficacy of infliximab
      in children with refractory SJIA.

PMID- 16095129
TI  - Serum levels of manganese superoxide dismutase in patients with mixed connective
      tissue disease.

PMID- 16095130
TI  - Expression of survivin in synovium and cartilage in DBA/1J mice with type II
      collagen-induced arthritis.

PMID- 16095131
TI  - Hydronephrosis and painless ascites: rare features of late-onset SLE.

PMID- 16095132
TI  - Fibromyalgia symptoms after treatment for Cushing's syndrome.

PMID- 16095133
TI  - On the cover: Honeybees.

PMID- 16095134
TI  - Need for better adherence to asthma guidelines in Chicago.

PMID- 16095135
TI  - Sesame allergy: a growing food allergy of global proportions?
AB  - OBJECTIVE: To present an up-to-date synopsis on the global prevalence, natural
      history, nature of allergens, and immune mechanisms of sesame allergy. DATA
      SOURCES: We performed a literature search using the PubMed database. We obtained
      information on regulatory issues from the Web pages of respective agencies. STUDY
      SELECTION: The PubMed search was performed using the algorithm sesame AND
      allergy. Date restriction was not used, and only articles in English were
      considered. The articles obtained were screened for additional references to work
      not obtained in the initial search. Each article was analyzed, and a pooled
      source of published information was generated. RESULTS: Evidence was found for
      increased reporting of sesame allergy during the past 5 decades, with reports
      mostly from developed countries. Clinically, most sesame allergy was presented in
      at least 2 major forms: (1) immediate hypersensitivity, often expressed as
      systemic anaphylaxis, associated with positive skin prick test and/or IgE
      antibody test results to sesame proteins with some cross-reactivity with other
      foods, and (2) delayed hypersensitivity to lignin-like compounds in sesame oil
      clinically expressed as contact allergic dermatitis. There were a few cases of
      immediate hypersensitivity to sesame with negative skin prick test and/or IgE
      antibody test results that were confirmed by oral challenge tests. CONCLUSIONS:
      Sesame allergy is a significant, serious, and growing problem. Evidence exists of
      the ability of protein and oil components of sesame to trigger immediate
      hypersensitivity via IgE antibody and delayed hypersensitivity via cell-mediated
      immune responses, respectively.

PMID- 16095136
TI  - A 62-year-old woman with 3 episodes of anaphylaxis.

PMID- 16095137
TI  - Asthma morbidity and treatment in the Chicago metropolitan area: one decade after
      national guidelines.
AB  - BACKGROUND: A number of studies have demonstrated disproportionate
      hospitalization and mortality rates in US urban areas. Yet, no published
      population-based studies have examined the burden of asthma on the residents of a
      particular urban area known to be at high risk for poor asthma outcomes.
      OBJECTIVES: To examine asthma morbidity and medical care in a population-based
      sample of adults and children with asthma residing in the greater Chicago, IL,
      metropolitan area and to explore social and demographic influences on morbidity
      and treatment. METHODS: A telephone survey of adults living in the Chicago
      metropolitan area was conducted from November 1999 through December 2000.
      RESULTS: The final sample included 152 adults and children with active asthma.
      Emergency department visits and hospitalizations for asthma in the previous year
      were reported by 25.7% and 6.6% of respondents, respectively. Of current
      medication users, 32.2% reported current regular use of controller medications.
      After adjusting for age, sex, income, education, and reported current
      pharmacotherapy, compared with white individuals, African American individuals
      remained 6.3 times more likely to have experienced an emergency department visit
      and 12.3 times more likely to have been hospitalized. CONCLUSIONS: These findings
      suggest that poorly controlled asthma remains a prevalent problem for persons
      with asthma in this metropolitan area and that a large gap remains between the
      goals of asthma therapy and appropriate treatment as defined by the National
      Asthma Education and Prevention Program. The reasons for disparate treatment and
      health outcomes by race/ethnicity and income need further study and intervention.

PMID- 16095138
TI  - Influence of sociodemographic factors on quality of life during pollen season in
      seasonal allergic rhinitis patients.
AB  - BACKGROUND: Quality of life (QOL) is an important outcome in asthma and seasonal
      allergic rhinitis (SAR), and its determinants are imperfectly understood. More
      specifically, the influence of sociodemographic factors on QOL in patients with
      SAR has been so far little investigated. OBJECTIVE: To examine the changes of QOL
      during the pollen season in patients with isolated SAR or SAR associated with
      asthma. METHODS: A prospective cohort study was conducted in southern France.
      Outpatients aged 18 to 60 years and regularly treated by respiratory physicians
      for SAR (with or without associated asthma) were identified. Patients were
      recruited before the grass or ragweed pollination period. At peak pollination,
      patients completed the French versions of the Mini Rhino-conjunctivitis Quality
      of Life Questionnaire (mini-RQLQ) and the 12-item Short-Form Health Survey (SF
      12) physical component summary (PCS) and mental component summary (MCS). RESULTS:
      A total of 135 patients was included, 83 with isolated SAR and 52 with associated
      asthma (mean age, 35.4 years; SD, 10.6 years; 56% female). At pollen peak, QOL
      scores were lower in women for all instruments, with significant effects on SF-12
      MCS and PCS scores in multivariate analyses. Likewise, a university-level
      education was an independent predictor of higher SF-12 PCS and MCS scores.
      Patients who lived in rural areas had significantly poorer QOL at pollen peak, as
      measured by the mini-RQLQ (P = .002) and SF-12 PCS (P = .008). No influence of
      age, presence of an animal at home, or smoking status could be identified on any
      QOL scores. CONCLUSIONS: Being a woman, living in the countryside, and having a
      lower education level were all independent predictors of poorer QOL of SAR
      patients. These factors must be taken into account when interpreting QOL of
      patients with SAR. Further studies are needed to confirm these results.

PMID- 16095139
TI  - Long-term use and tolerability of cyclooxygenase-2 inhibitors in patients with
      analgesic intolerance.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) inhibitors are reported to be well tolerated
      in patients with analgesic intolerance (AI). However, limited data are available
      about the long-term tolerability of these drugs. OBJECTIVE: To determine the long
      term tolerability of COX-2 inhibitors in patients with Al. METHODS: Patients with
      AI who previously underwent single-masked, placebo-controlled oral provocation
      tests and were found to tolerate nimesulide, meloxicam, rofecoxib, or celecoxib
      were interviewed regarding the long-term use and tolerability of these drugs.
      RESULTS: Of 87 patients, 61 (70%) had used the recommended COX-2 inhibitor(s). Of
      the 61 users, 54 (89%) tolerated the drug(s) well and 7 (11%) reported adverse
      events. Three patients reporting adverse events were rechallenged with the
      responsible COX-2 inhibitor, and their results were found to be negative.
      CONCLUSIONS: Long-term use of COX-2 inhibitors was tolerated well by most
      patients with AI, and placebo-controlled oral provocation tests, as a single
      test, seemed to predict tolerability. Furthermore, self-reported positive
      reactions in the long-term should also be confirmed with rechallenge tests for
      definite diagnosis.

PMID- 16095140
TI  - Induction of interleukin 10 by sublingual immunotherapy for house dust mites: a
      preliminary report.
AB  - BACKGROUND: Subcutaneous specific immunotherapy has been demonstrated to be
      capable of inducing T-cell regulatory response. Interleukin 10 (IL-10) plays a
      crucial role in inducing allergen-specific tolerance; however, no previous
      studies have examined IL-10 production after sublingual immunotherapy (SLIT).
      OBJECTIVE: To evaluate T-cell proliferation and IL-10 production in patients
      successfully treated with SLIT for house dust mites (HDMs). METHODS: Peripheral
      blood mononuclear cells were isolated from patients after at least 3 years of
      successful HDM SLIT and from matched untreated allergic patients and healthy
      control subjects. After 3 and 6 days of in vitro stimulation with
      phytohemagglutinin (PHA), Candida albicans, and Dermatophagoides farinae,
      proliferation and production of IL-10 were measured. RESULTS: Patients treated
      with SLIT showed a significant reduction of proliferation induced by C albicans
      compared with untreated atopic patients (P < .001), but a significant reduction
      was also demonstrated in healthy controls compared with untreated atopic patients
      (P < .001). Patients treated with SLIT also showed a significant increase of IL
      10 production after Candida and PHA stimuli compared with patients with untreated
      rhinitis (P < .001 for both). Patients with untreated rhinitis did not produce IL
      10. CONCLUSION: This preliminary study confirms reduced T-cell proliferation and
      preliminarily provides the first evidence, to our knowledge, of peripheral IL-10
      production in allergic patients successfully treated with HDM SLIT.

PMID- 16095141
TI  - Cross-reactivity among edible nuts: double immunodiffusion, crossed
      immunoelectrophoresis, and human specific igE serologic surveys.
AB  - BACKGROUND: As many as one third of all food allergen anaphylactic events are
      related to tree nut ingestion. Although concurrent allergen sensitivity to tree
      nuts is common, cross-reactivity among nut antigens is less well defined.
      OBJECTIVE: To survey serologic cross-reactivities among 7 tree nuts (walnut,
      pecan, hazelnut, cashew, Brazil nut, pistachio, and almond) and peanut. METHODS:
      Human specific IgE enzyme-linked immunosorbent assay inhibition was used to
      identify nut allergen cross-reactivities. Single-nut rabbit antisera were used in
      double immunodiffusion, crossed-line immunoelectrophoresis, and crossed
      immunoelectrophoresis with intermediate gel studies of nut antigen cross
      reactivity. RESULTS: Nut specific IgE enzyme-linked immunosorbent assay
      inhibition demonstrated no cross-reactivities between peanut and tree nuts. Among
      tree nuts, 2 groups with allergen cross-reactivity were defined: (1) walnut,
      pecan, and hazelnut and (2) hazelnut, cashew, Brazil nut, pistachio, and almond.
      Double immunodiffusion, crossed-line immunoelectrophoresis, and crossed
      immunoelectrophoresis with intermediate gel results supported the same groupings
      of cross-reactive tree nuts and identified several less prominent nut-nut antigen
      cross-reactivities between groups and with peanut. CONCLUSION: With few
      exceptions (notably limited peanut cross-reactivity with pistachio and walnut),
      peanut antigens did not serologically cross-react with tree nuts. Walnut, pecan,
      and hazelnut form a group of strongly cross-reactive tree nuts. Hazelnut, cashew,
      Brazil nut, pistachio, and almond form a group of moderately cross-reactive tree
      nuts. Cross-reactivities between these groups are less pronounced (notably
      limited cross-reactivity of walnut and pecan with Brazil nut). The strongest
      cross-reactivities among tree nuts follow botanical family associations: (1)
      walnut and pecan in the family Juglandaceae and (2) cashew and pistachio in the
      family Anacardiaceae.

PMID- 16095142
TI  - Validation of the Spanish and English versions of the asthma portion of the Brief
      Pediatric Asthma Screen Plus among Hispanics.
AB  - BACKGROUND: The health and health care needs of non-English-speaking Hispanic
      families with children are poorly understood, in part because they are often
      excluded from research owing to language barriers. Instruments that are valid in
      English and Spanish are necessary to accurately evaluate the magnitude of asthma
      prevalence and morbidity among Hispanics. OBJECTIVE: To establish the sensitivity
      and specificity of the English and Spanish versions of the asthma portion of the
      Brief Pediatric Asthma Screen Plus (BPAS+) in a low-income Hispanic population.
      METHODS: The validation sample consisted of 145 children whose parents completed
      the BPAS+ in Spanish and 78 whose parents completed it in English. Bilingual
      clinicians conducted the examinations on which the clinical assessments were
      based. We compared the BPAS+ results with the clinical assessment findings to
      determine the sensitivity and specificity of the BPAS + among Hispanics in terms
      of identifying children who warrant further medical evaluation for asthma.
      RESULTS: The sensitivity and specificity of the asthma portion of the Spanish
      BPAS+ were 74% and 86%, respectively. The sensitivity and specificity of the
      asthma portion of the English BPAS+ were 61% and 83%, respectively. CONCLUSIONS:
      The asthma portion of the BPAS+, a valid screen for identifying children who are
      in need of further evaluation for potentially undiagnosed asthma, is valid for
      low-income Hispanics in Spanish and English. As the Hispanic population continues
      to grow, it is imperative that researchers have English and Spanish instruments
      that are valid for this population.

PMID- 16095143
TI  - Atopy and contact hypersensitivity: a reassessment of the relationship using
      objective measures.
AB  - BACKGROUND: There is a big contradiction in the medical literature regarding the
      relationship between atopy and contact hypersensitivity. Some researchers believe
      that atopy would prevent, whereas others believe that it would promote, the
      development of contact allergy. Possible causes of this confusion range from
      different study populations to different definitions of atopy. OBJECTIVE: To
      evaluate the relationship between atopy and contact hypersensitivity in a well
      defined general population sample using objectively measurable markers. METHODS:
      I studied 135 randomly selected students from 5 vocational schools: 73 women and
      62 men aged 18 to 19 years. The following atopy markers were tested: positive
      skin prick test results, positive Phadiatop test results, and total IgE levels
      greater than 120 kU/L. Contact hypersensitivity was detected by using patch
      tests. Statistical analyses included the Fisher exact test, the Mann-Whitney U
      test, and calculation of odds ratios. RESULTS: At least 1 positive skin prick
      test result was found in 23.7% (95% confidence interval [CI], 16.5%-30.9%) of
      study participants, positive Phadiatop test results were found in 20.0% (95% CI,
      13.3%-26.7%), and total IgE levels greater than 120 kU/L were found in 23.7% (95%
      CI, 16.5%-30.9%). Positive patch test reactions were found in 28.1% (95% CI,
      20.6%-35.7%) of participants, most frequently to thimerosal (18.5%; 95% CI, 12.0%
      25.1%) and nickel (9.6%; 95% CI, 4.6%-14.6%). For persons with atopy markers,
      odds ratios for contact hypersensitivity ranged from 1.0 to 3.2, the highest
      being for nickel hypersensitivity among those with total IgE levels greater than
      120 kU/L. None of these relationships were statistically significant. CONCLUSION:
      Atopy and contact hypersensitivity are independent phenomena.

PMID- 16095144
TI  - The safety of twice-daily treatment with fluticasone propionate and salmeterol in
      pediatric patients with persistent asthma.
AB  - BACKGROUND: For children older than 5 years with asthma who remain symptomatic
      despite inhaled corticosteroid (ICS) therapy, the preferred treatment is to add
      an inhaled long-acting beta2-agonist vs increasing the ICS dose. OBJECTIVE: To
      compare the safety of twice-daily treatment with inhaled fluticasone propionate
      plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone
      propionate used alone in children aged 4 to 11 years with persistent asthma.
      METHODS: A randomized, multicenter, double-blind, active-controlled, parallel
      group study in 203 children with persistent asthma who were symptomatic during
      ICS therapy. Patients received fluticasone propionate-salmeterol (100/50 microg)
      or fluticasone propionate (100 microg) alone twice daily for 12 weeks. RESULTS:
      The safety profile of fluticasone propionate-salmeterol was similar to that of
      fluticasone propionate alone. The overall incidence of adverse events was 59% for
      fluticasone propionate-salmeterol and 57% for fluticasone propionate. Both
      treatments were well tolerated. Two patients receiving fluticasone propionate
      salmeterol and 5 receiving fluticasone propionate withdrew from the study because
      of worsening asthma. Changes in heart rate, blood pressure, and laboratory
      variables were infrequent and were similar between treatments. No patients had
      clinically significant abnormal electrocardiographic findings during treatment.
      Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks
      of treatment was comparable within and between groups; no patient in either group
      had abnormally low 24-hour urinary cortisol excretion after 12 weeks of
      treatment. The incidence of withdrawals due to asthma exacerbations was 2% in the
      fluticasone propionate-salmeterol group and 5% in the fluticasone propionate
      group. CONCLUSIONS: In pediatric patients with persistent asthma, fluticasone
      propionate-salmeterol twice daily was well tolerated, with a safety profile
      similar to that of fluticasone propionate used alone.

PMID- 16095145
TI  - The effect of natural pollen exposure on eosinophil apoptosis and its
      relationship to bronchial hyperresponsiveness in patients with seasonal allergic
      rhinitis.
AB  - BACKGROUND: Limited data suggest that there is increased eosinophilic
      inflammation in the airways of patients with seasonal allergic rhinitis (SAR)
      during pollen season even if they do not have asthma. OBJECTIVE: To investigate
      the effect of natural pollen exposure on inflammatory cells and apoptosis of
      eosinophils and its association with bronchial hyperresponsiveness (BHR) during
      and out of pollen season in SAR patients sensitized to only grass pollens.
      METHODS: Forty SAR patients and 10 patients with nonallergic rhinitis (NAR) from
      Ankara, Turkey, were recruited to participate in the study. Two induced sputum
      samples were taken from SAR patients during pollen season (May-June) and out of
      pollen season (November-January), but only 1 induced sputum sample was taken from
      NAR patients. Slides of induced sputum were evaluated by 2 cytologists with the
      use of light microscopy after cytocentrifuged and dyed with May-Grunwald-Giemsa
      stain. Induced sputum samples were sufficient for differential cell counts in 14
      SAR and 7 NAR patients. RESULTS: Eosinophil counts in SAR patients were
      statistically higher in pollen season (19.4% +/- 16.2%) compared with out of
      season (4.6% +/- 6.9%, P = .003) and with NAR patients (4.7% +/- 9.5%, P = .01).
      The apoptotic eosinophil counts in SAR patients were statistically higher out of
      pollen season (3.0% +/- 4.5%) than in pollen season (0.38% +/- 0.80%, P = .02)
      and higher than those of NAR patients (0.14% +/- 0.26%, P = .005). The apoptotic
      ratio was statistically higher after pollen season compared with pollen season
      (0.720% +/- 0.394% vs 0.044% +/- 0.116%, P = .002). Blood eosinophil counts of
      SAR patients were increased during the pollen season (364 +/- 187/mm3) compared
      with out of season (278 +/- 219/mm3, P = .04) and with NAR patients (85 +/-
      54/mm3, P = .001). The number of SAR patients who had BHR during the pollen
      season (7/14) was higher than the number who had BHR out of season (2/14, chi2 =
      4.2, P = .04). CONCLUSION: Our data indicate that changes in eosinophil counts
      and eosinophil apoptosis may be related to the changes of natural pollen exposure
      and seasonal changes of BHR in SAR patients.

PMID- 16095146
TI  - Effects of the Chinese herbal formula Shi-Bi-Lin on cytokine release from the
      human mast cell line.
AB  - BACKGROUND: The traditional Chinese herbal formula Cang Er Zi San has been used
      for the treatment of rhinitis, paranasal sinusitis, and allergic rhinitis for
      several centuries. However, its therapeutic mechanisms remain largely unclear.
      OBJECTIVE: To study the effects of Shi-Bi-Lin (SBL), a modified Cang Er Zi San
      formula, on cytokine release from and expressions in the human mast cell line
      (HMC-1). METHODS: The HMC-1 was preincubated with different concentrations of SBL
      extract solution 1 hour before being stimulated with 25 ng/mL of phorbol
      myristate acetate plus 2.5 x 10(-7)M calcium ionophore A23187 and then further
      incubated for 6, 12, and 24 hours, respectively. The cell culture supernatants
      were harvested, and the cytokines of interleukin 4 (IL-4), IL-6, IL-8, and tumor
      necrosis factor alpha (TNF-alpha) in the supernatants were measured by enzyme
      linked immunosorbent assay. Furthermore, the total RNA of the cells was
      extracted, and the cytokines' messenger RNA expressions were examined using
      semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: After
      different incubation periods at different concentrations, SBL could potently
      inhibit the cytokines of IL-4 and TNF-alpha and modestly affect IL-6 but not
      obviously affect IL-8 release from the HMC-1. However, no inhibitory effects were
      detected on the messenger RNA expressions of these cytokines. CONCLUSIONS: These
      results demonstrate that SBL could modulate the mast cell-mediated
      hypersensitivity reaction in allergy. Inhibition of mast cell-derived IL-4 and
      TNF-alpha might explain the efficacy of SBL in treating allergic disease.

PMID- 16095147
TI  - Total eosinophil cationic protein levels in induced sputum as a marker of changes
      in eosinophilic inflammation in a patient with allergic asthma.
AB  - BACKGROUND: Counting eosinophils in induced sputum seems to be a better way to
      survey disease activity than indirect clinical assessments of airway
      inflammation, such as pulmonary function measurement. The conventional analysis
      of induced sputum, however, is time-consuming and requires skilled personnel,
      which have restricted its use. OBJECTIVE: To determine whether measuring
      eosinophil cationic protein (ECP) levels in the entire sputum sample could
      replace the method of counting eosinophils and measuring ECP levels in the
      supernatant only to establish a clinically more applicable method of studying the
      intraindividual changes in eosinophilic activity in induced sputum. METHODS: In
      13 patients with mild, nonsymptomatic allergic asthma, sputum was induced before
      and 24 hours after allergen challenge. The entire sputum sample was diluted with
      0.1% dithiothreitol, incubated, and divided into 2 parts. One part was processed
      according to the conventional method, and released ECP levels in the supernatant
      were measured. The second part was treated with a lysing reagent. Cell debris was
      separated, and total (intracellular and extracellular) ECP levels in the solution
      were measured. RESULTS: We found good correlation between total ECP levels in the
      entire sputum sample and released ECP levels in the supernatant before (r = 0.97)
      and 24 hours after (r = 0.99) allergen challenge (P < .01 for both). We also
      found a good correlation between the changes in total and released ECP levels (r
      = 0.99; P < .01). CONCLUSIONS: Total ECP concentration seems to reflect the
      eosinophilic inflammatory changes in asthma and might be a useful tool in
      clinical practice.

PMID- 16095148
TI  - Hyper-IgM1 syndrome with interstitial pneumonia and diarrhea caused by
      coxsackievirus B4 in a 3-month-old infant.
AB  - BACKGROUND: Hyper-IgM1 syndrome is a rare genetic primary immunodeficiency
      disease caused by mutations of the CD40 ligand gene. It is characterized by
      normal or elevated levels of IgM and markedly decreased serum IgG, IgA, and IgE
      levels. Patients with this syndrome often easily develop infections. During the
      past decade, it has become clear that enteroviral infections may also occur as a
      manifestation of hyper-IgM1 syndrome. OBJECTIVE: To report a case of hyper-IgM1
      syndrome in a 3-month-old boy who had interstitial pneumonia and intractable
      diarrhea. METHODS: Chest radiography, bronchoscopy, immune studies, and open lung
      biopsy were performed. RESULTS: Chest radiography revealed diffuse bilateral
      infiltrates. Immune studies revealed the following proportions of lymphocyte
      markers: CD3, 5,976/microL; CD4, 5,015/microL; CD8, 866/microL; CD19,
      1,325/microL; CD16 + 56, 935/microL; and active T cells, 225/microL. The IgG
      level was 190 mg/dL; IgA, 2 mg/dL; IgM, 34 mg/dL; IgE, 1 IU/dL; and CH50,
      23.8/mL. CD40L expression was less than 1%, and a Tyr 169 Asn (t526a) mutation in
      the exon 5 tumor necrosis factor domain of the CD40L gene was found. The patient
      was treated with intravenous immunoglobulin and had a dramatic improvement in
      symptoms. Open lung biopsy failed to demonstrate pneumocystis, and there was no
      evidence of cryptosporidium in the stool. However, coxsackievirus B4 was isolated
      by viral throat culture. CONCLUSION: Interstitial pneumonia and diarrhea caused
      by coxsackievirus B4 may be a complication of hyper-IgM1 syndrome.

PMID- 16095149
TI  - [Urinary tract infections in outpatients treated in 2002-2003].
AB  - The aim of this study was to isolate, identify and determine a drug
      susceptibility of bacterial uropathogens cultured from outpatients in 2002-2003.
      In total, 4211 urine samples were examined, among which 1942 were positive. 2086
      bacterial strains were cultured. Escherichia coli strains (1094) dominated, which
      were etiological agents of over a half of urinary tract infections (UTIs).
      Uropathogens isolated from outpatients were susceptible to many antibacterial
      agents.

PMID- 16095150
TI  - [The content of nitrates III and V in mineral table water and in medicinal
      waters].
AB  - In this study we assessed the content of nitrates III and V in the 11 sorts of
      mineral table waters and 7 sorts of the healing waters. The spectrophotometry
      Griess and Ilosvay' method with cadmium column according to Polish standards was
      used. We found the presence of nitrates V in all investigated types of waters.
      18% of investigated mineral table waters and 40% of healing mineral waters
      contain nitrates III.

PMID- 16095151
TI  - [Progressive physical disability, pain and quality of life of patients with
      rheumatoid inflammation of the joints].
AB  - WHO pronounced years 2000-2010 the Decade of Bones and Joints--the main purpose
      of which is the improvement of the quality of life of patients suffering from
      inflammatory movement organ condition. A chronic disease leading to disability,
      handicap and even premature death is progressive rheumatoid arthritis (RA).
      Irreversible changes in the joints develop during the first years of RA. For the
      patient it results in certain ailments, physical disorders, lowering of the level
      of health and the quality of life. The purpose of the thesis was: specifying
      health problems of patients suffering from RA; evaluation of the level of
      physical disability along with patient's quality of life; defining both
      educational and caring tasks contributing to the improvement of the quality of
      life of the patient and preparation of the patient and their family to self-care.
      Patient suffering from RA demands professional manifold care and complex
      therapeutic actions. It is the patient themselves, however, who decides to what
      extent they allow the disease to control their lives or how much they control the
      disease themselves. Patient and their family need advice and support in the first
      stage of illness but also throughout the disease, in order to adapt to patient's
      changing health conditions--disorganizing and disordering physical, psychological
      and social functioning of the patient. Ascertaining the factors determining
      attitudes and aspirations of the patient may lead to achieving conditions
      influencing the improvement of the quality of their lives.

PMID- 16095152
TI  - [Soluble tumor-necrosis-factor-alpha receptor type-1 as a marker of activity of
      psoriasis vulgaris and effects of its treatment].
AB  - The aim of the study was to examine the concentration of soluble tumor necrosis
      factor alpha type I (sTNF-R1) in patients with psoriasis vulgaris in relation to
      the severity of skin lesions and the effects of treatment. PATIENTS AND METHODS:
      the study was conducted among 34 patients. The assessment of the severity of skin
      lesions (Psoriasis Area and Severity Index -PASI), and the serum concentration of
      sTNF-R1 (ELISA) were performed at baseline and after 2 weeks of treatment.
      Control sera were obtained from 30 healthy volunteers. RESULTS: pretreatment PASI
      was 12.98 +/- 5.77 and after two-week treatment 6.17 +/- 2.12 (p < 0.05), sTNF-R1
      concentration 1.88 +/- 0.41 ng/mL and 1.65 +/- 0.46 ng/mL, respectively (p <
      0.05). Serum concentration of sTNF-R1 was significantly lower in controls (1.48
      +/- 0.30 ng/mL) as compared with its pre-treatment level in psoriasis patients. A
      significant correlation between pre-treatment PASI and concentration of sTNF-R1
      was found (r = 0.40, p < 0.05). CONCLUSION: serum concentration of sTNF-R1 can be
      a sensitive marker of activity of psoriasis vulgaris and decreases following the
      effective treatment.

PMID- 16095153
TI  - [Tissue factor and tissue factor pathway inhibitor during specific bronchial
      challenge in allergic asthma patients].
AB  - Allergic asthma is characterized by bronchial inflammation and repair processes
      at the same time, that cause increased airway obstruction. Recent evidences
      suggest that monocytes and macrophages may play important role in allergic
      inflammation. Activated by proinflammatory factors they can express tissue factor
      (TF) and tissue factor pathway inhibitor (TFPI). The aim of the present study was
      to evaluate TF and TFPI in plasma of bronchial asthma patients. The study was
      performed on 17 asthma patients with documented Dermatophagoides pteronyssinus
      (Dp) allergy. 15 healthy persons served as negative control. Specific bronchial
      challenge with Dp extracts was performed in asthma patients. Blood was collected
      before allergen challenge--A0, during the early asthmatic reaction (EAR)--A0
      during the late asthmatic reaction (LAR)--A2, and 24 hours after administration
      of the first allergen dose--A3. The concentrations of TF and TFPI were measured
      by ELISA method. The concentration of TF in asthmatic patients was significantly
      higher as compared with healthy controls. In patients that developed only EAR,
      the concentration of TF increased at A1, then decreased at time when LAR should
      be developed (A2) and it was comparable with beginning values 24 hours after
      starting the challenge. In patients that developed EAR and LAR, the mean TF
      concentration increased during EAR (A,) with subsequent decline during LAR (A2).
      24 hours after starting the challenge the TF concentration was higher than
      beginning values (A3). The concentration of TFPI in patients that developed only
      EAR was significantly higher than the values in healthy controls. It decreased
      during EAR (A1) and increased 24 hours after starting the challenge (A3). The
      mean concentration of TFPI in patients that developed EAR and LAR was not
      significantly higher than the values in healthy controls. It increased during EAR
      and LAR with the highest values 24 hours after starting the challenge.
      Coagulation system seems to be activated during allergic inflammation after
      allergen challenge. Increased levels of TF and TFPI in asthma patients may be
      connected with chronic bronchial inflammation and remodeling of bronchial wall.

PMID- 16095154
TI  - [Transbronchial needle aspiration as a diagnostic method of mediastinal
      adenopathy].
AB  - The aim of the study was to assess the diagnostic yield of transbronchial needle
      aspiration (TBNA) in mediastinal or hilar adenopathy in: sarcoidosis,
      tuberculosis and malignancy. Transbronchial needle aspiration was performed in 53
      patients, preeceded by computed tomography (CT). In 22 patients (41,5%) TBNA
      enabled to diagnose 10 cases of sarcoidosis, 12 cases of neoplastic infiltrates
      of the lung. There were 31 cases undiagnosed by means of TBNA. In 24 patients the
      diagnosis was established by means of other methods like bronchoscopy with mucose
      biopsy (8 cases of sarcoidosis), transbronchial lung biopsy (4 cases of squamous
      cell carcinoma and adenocarcinoma, 2 cases of sarcoidosis), mediastinoscopy (3
      cases of sarcoidosis and 2 cases of Hodgkin's disease), and videothoracoscopy (2
      cases of sarcoidosis), transthoracic needle biopsy (1 case of squamous cell
      carcinoma) and lymph node biopsy (1 case of adenocarcinoma and 1 case of
      sarcoidosis). In the remaining 7 patients who were followed-up for a period of
      one year the diagnosis of sarcoidosis was confirmed by clinical, radiological and
      cytological (BAL) examinations. Transbronchial needle aspiration was shown to be
      efficient diagnostic method in mediastinal or hilar adenopathy in sarcoidosis and
      malignancy except lymphoma. Moreover in approximately 60% of cases this technique
      doesn't allow to establish a diagnosis and in turn implicates the necessity for
      further diagnostic procedures like mediastinoscopy, or transbronchial or
      thoracoscopic lung biopsy.

PMID- 16095155
TI  - [Mechanical bowel obstruction. Surgical problem at the turn of the XIX-XX
      century, and the XX-XXI century. One institutional experience].
AB  - Comparative analysis was done between a group of 193 patients operated on for
      mechanical bowel obstruction at the end of the XIX century (prof. A Obalifinski's
      clinical material), and a group of 207 patients with the same condition operated
      on between 1.01.1999 - 31.12.2003 (own clinical material). Both groups were
      operated on at the same surgical institution. A hundred years ago, and at present
      mechanical bowel obstruction has been appearing (depending on a patient's sex),
      in the 1:1 relationship. In both analysed periods two third of the patients
      developed small bowel obstruction, and one third large bowel obstruction. At the
      end of the XIX century mean age of the operated patient was 41 years. It was
      equal to the mean survival time span for the general population at that time. The
      patients operated on at present were about 25 years older. However their mean age
      is significantly lower compared with the actual mean survival time span for the
      general population observed now in Poland. In small bowel the main cause of
      obstruction has still been an incarcerated abdominal hernia (increase from 30.7%
      up to 55%), followed by intraperitoneal adhesions (increase from 29.5% up to
      34.5%). However their etiology has changed, recently all of them are
      postoperative adhesions. At the end of the XX century we observed significant
      drop (from 16.8% to 2.7%) in strangulation of the small bowel mesentery as a
      cause of obstruction. In case of large bowel during the last century there was a
      definitive change in frequency of different etiological factors causing
      obstruction. In the XIX century 72% of them was caused by mesentery strangulation
      of sigma or cecum. whereas at present over 80% of them is caused by cancer. We
      presented Prof. A. Obalinski's and his associates scientific output, as they were
      genuine precursors of mechanical bowel obstruction surgery in Poland.

PMID- 16095156
TI  - [Possibilities of data acquisition, recording and processing based on the system
      for continuous intracranial pressure and cerebral perfusion pressure monitoring
      designed at the Department of Neurosurgery of the Jagiellonian University in
      Cracow].
AB  - OBJECTIVES: To describe computer system for intracranial pressure (ICP)
      monitoring and for infusion testing (IT), and to present current possibilities of
      analysis of cerebrospinal fluid (CSF) pressure signal. SYSTEM DESCRIPTION:
      Computer system for pressure signal measurement and acquisition consists of three
      sensors: for ICP, infusion pressure during IT, and blood pressure measurements.
      Electric signal from the sensors is transmitted to Temed RMN-201M cardiomonitor,
      and next after enhancement is subjected to Data Shuttle DS-12-8-5B-AO analog to
      digital converter. Digital output signal is recorded and analysed'on standard
      personal computer. Original Windows-compatible software was developed to control
      the system. The program consists of three blocs: configuration, measurement and
      readout, and enables selection of voltage range for each of the signal channels,
      measurement resolution, sampling frequency, calibration and zeroing of the
      sensors, visualisation of pressure signals on graph, data storage in text format
      and automatic analysis of IT. Main characteristics of the system include: high
      sampling frequency (up to 500 Hz), simultaneous data recording from all signal
      channels, and access to terminal cistern with one puncture needle on IT.
      Laboratory and clinical tests confirmed high precision of the developed system.
      ICP CURVE ANALYSIS: The developed software allows for evaluation of the main
      parameters, of CSF dynamics, prediction of IT course before a steady state is
      reached as well as spectral analysis of pressure signal. CONCLUSIONS: Computer
      measurement system developed at our department is clinically useful and allows
      for high precision signal acquisition necessary for advanced scientific analyses
      of hydrocephalus and intracranial pressure.

PMID- 16095157
TI  - [Experimental methods in the treatment of multiple sclerosis--new possibilities
      and hopes].
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system (CNS) leading to demyelinization. Although our knowledge on the
      pathomechanism of MS has evolved dramatically in recent years; however there is
      still no effective cure for MS. So far, non-specific immune suppressive agents
      are used to slow down the disease. Recently, there are many efforts to find a new
      method that would allow to control specifically unwanted immune response. It
      might be achieved by affecting antigen recognition or induction of "immune
      deviation".

PMID- 16095158
TI  - [The role of metalloproteinases in psoriasis].
AB  - Metalloproteinases play a crucial role in the destruction processes related to
      inflammation and carcinogenesis as well as in wound healing, morphogenesis and
      growth. Destruction of extracellular matrix proteins related to these enzymes
      activity and following damage of basement membranes favour angiogenesis and
      inflammatory infiltrations in psoriasis. Metalloproteina-ses activity can be
      controlled on different levels: genetic expression, enzyme activation or its
      inhibition. In this paper we discuss recently discovered role of
      metalloproteinases in the pathogenesis of skin diseases, including psoriasis. The
      most interesting seems to be results of research on possible application of
      metalloproteinases inhibitors in psoriasis treatment and usefulness of these
      enzymes measurement in the management of this disease.

PMID- 16095159
TI  - [Immunological mechanisms of celiac disease].
AB  - Celiac disease results from genetic abnormal immune response to gluten. This
      leads to local activation of immune system. There are several clinical
      manifestations of the disease (e.g. active, silent and latent). Fundamental
      processes of celiac disease occur in small intestine mucosa. As a result of
      immunological reactions the development of inflammatory process with typical
      histopathological lesions is observed. In pathogenesis of celiac disease
      immunological cellular response with significant role of T lymphocytes is of
      great importance. According to one hypothesis in the disease non proliferative
      activation of lamina propria CD4+ lymphocytes and proliferative activation of
      intra-epithelial TcR alpha/beta CD8+ and TcR gamma/delta lymphocytes is
      postulated. Probably in immunological reaction to gluten besides T lymphocytes
      other cells are involved (lymphocytes B, NK cells, neutrophils, eosinophils,
      macrophages, mastocytes) but their role was not clearly established. Recently in
      pathogenesis of celiac disease participation of cytokines produced locally in
      small intestine is often emphasized.

PMID- 16095160
TI  - [Effect of drugs on the diagnostic laboratory tests results].
AB  - The results of clinical laboratory determinations depend on physiological,
      environmental and pharmacological factors. Thousand pharmacological factors used
      daily, are known to interfere with routine laboratory tests by pharmaco
      toxicological and physico-chemical reactions. This confusing interference may
      cause the wrong diagnoses but also incorrect treatment, unnecessary tests and
      further costs. Even if we would be able to recognize the most important effects
      of drugs, we will not be able to remember all of the drugs adverse reactions;
      therefore use of computer databases could be helpful for interpreting doubtful
      laboratory test results.

PMID- 16095161
TI  - [Whooping cough in a previously vaccinated patient--case report].
AB  - Pertussis is an acute contagious human disease caused by gram-negative
      Coccobacilli Bordetella pertussis. Numerous factors and toxins produced by
      Bordetella pertussis play important role in pathogenicity of the disease. Typical
      illness has three clinical stages: catarrhal, paroxysmal and convalescent. In
      therapy erythromycin is the antibiotic of choice. We present a case of pertussis
      in a seventeen year old, previously vaccinated patient.

PMID- 16095162
TI  - [Sildenafil reduces pressure and pulmonary resistance and increases
      susceptibility of pulmonary arteries to nitric oxide in primary pulmonary
      arterial hypertension].
AB  - Primary pulmonary arterial hypertension (PPH) is a rare disease of undetermined
      origin and fatal prognosis. A better prognosis is associated with at least 20%
      reduction of either pulmonary artery pressure or pulmonary vascular resistance
      ("responders") in acute vasodilatory trials. Prostacycline (PGI2) or nitric oxide
      (NO) administration promises valuable results. NO is one of the most powerful
      vasodilating agents, endogenously produced by endothelial cells. It migrates from
      these cells to smooth muscle cells and stimulates production of cGMP, that
      induces smooth muscle relaxation. cGMP is hydrolyzed by 5-phopshodiesterase (PDE
      5). Several papers documenting hypotensive effect in pulmonary circulation of
      specific PDE5 inhibitor--sildenafil (Viagra--Pfizer) have been published
      recently. We present a case report of a 26 year old female patient with PPH-
      "nonresponder" in a trial with NO--and NO responder after sildenafil
      administration. Initial values were: mean pulmonary artery pressure (mPAP) was 58
      mmHg, pulmonary vascular resistance was 10.9 Wood's units. mPAP and PVR during NO
      inhalation (40 ppm) decrease from 62 to 54 mmHg and from 11.4 to 10.3 Wood's
      units, respectively. Measurements performed 60 minutes after 50 mg of sildenafil
      orally disclosed a 19% reduction of mPAP and 21% reduction of PVR. NO inhalation
      caused further decrease of both parameters: mPAP was decreased for additional 28%
      and PVR for additional 36% in comparison to initial results. Neither peripheral
      hypotension nor other side effects were observed. A month-long administration of
      sildenafil in a dose 2 x 25 mg daily reduced mPAP and PVR to values reported for
      the acute trial. Physical capability improved also. It was assessed as increased
      distance in a six-minute-walk test (280 vs. 400 m in the first week of treatment,
      and 330 m in a fourth week of treatment). Echocardiography showed moderate
      decrease of right ventricle and right atrium diameters, along with decrease of
      the degree of relative tricuspid regurgitation with unchanged maximal velocity of
      regurgitant wave. Specific PDE-5 inhibitors might be an attractive alternative in
      the treatment of pulmonary hypertension in case the above noted observations are
      confirmed.

PMID- 16095163
TI  - [One name, two physicians. About Whipple's procedure and Whipple's disease].
AB  - The biographical silhouettes of two contemporary, but unrelated American
      physicians using the same name: Allen Oldfather Whipple and Gorge Hoyt Whipple
      are presented. Both significantly influenced their medical specialties. A.O.
      Whipple was a pioneer in modern surgery of the pancreas. His name is used as an
      eponym for resection of the pancreas head (Whipple's procedure). G.H. Whipple,
      the pathologist and physiologists received the Nobel Prize for his input into
      scientific evidence for the treatment of anemia. His name serves as an eponym for
      extremely rare disease of the bowel (Whipple's disease).

PMID- 16095164
TI  - Has Stewart finally arrived in the clinic?

PMID- 16095165
TI  - Thyroid sonography as an effective tool to discriminate between euthyroid sick
      and hypothyroid dogs.
AB  - The diagnosis of canine hypothyroidism and its differentiation from euthyroid
      sick syndrome still is a major diagnostic challenge. In this study,
      ultrasonography was shown to be an effective tool for the investigation of
      thyroid gland diseases. Healthy control dogs (n = 87), dogs with euthyroid sick
      syndrome (n = 26), thyroglobulin autoantibody-positive (TgAA-positive, n = 30)
      hypothyroid dogs, and TgAA-negative (n = 23) hypothyroid dogs were examined by
      thyroid ultrasonography. Maximal cross sectional area (MCSA), thyroid volume, and
      echogenicity were measured. Statistical analysis identified highly significant (P
      < .001) differences between euthyroid and hypothyroid dogs both in thyroid volume
      and in MCSA, whereas no significant differences in thyroid size were detected
      between healthy euthyroid dogs and dogs with euthyroid sick syndrome. In
      euthyroid and euthyroid sick dogs, parenchymal echotexture was homogeneous and
      hyperechoic, whereas relative thyroid echogenicity of both TgAA-positive and TgAA
      negative hypothyroid dogs was significantly lower (P < .001). When using
      arbitrarily chosen cutoff values for relative thyroid volume, MCSA, and
      echogenicity, thyroid volume especially was found to have highly specific
      predictive value for canine hypothyroidism. In summary, the data reveal that
      thyroid sonography is an effective ancillary diagnostic tool to differentiate
      between canine hypothyroidism and euthyroid sick syndrome.

PMID- 16095166
TI  - Ultrasonographic evaluation of the thyroid gland in healthy, hypothyroid, and
      euthyroid Golden Retrievers with nonthyroidal illness.
AB  - Ultrasound evaluation of the thyroid gland was performed in healthy, hypothyroid,
      and euthyroid Golden Retriever dogs with nonthyroidal illness (NTI) to determine
      the diagnostic usefulness of ultrasound for differentiating between euthyroid and
      hypothyroid dogs. Thirty-six healthy, 11 hypothyroid, and 35 euthyroid dogs with
      NTI were evaluated. Each thyroid lobe was examined ultrasonographically for size,
      shape, echogenicity, and homogeneity. Thyroid lobe volume was estimated by using
      the equation for an ellipsoid: pi/6(length X height x width). No differences were
      found between healthy dogs and euthyroid dogs with NTI. In the majority of
      euthyroid dogs, the thyroid lobes were fusiform and triangular in shape in
      longitudinal and transverse planes, respectively. The thyroid capsule appeared
      smooth. The thyroid parenchyma had a homogeneous echogenic pattern and usually
      was hyperechoic or isoechoic compared with the surrounding musculature.
      Ultrasound findings in hypothyroid dogs were more variable, including a greater
      frequency of round to oval-shaped thyroid lobes in the transverse imaging plane
      (P < .05), hypoechogenicity of the thyroid parenchyma compared with surrounding
      musculature (P < .001), and a decrease in the size and volume of the thyroid
      lobes and total volume of the thyroid gland (P < .05) compared with euthyroid
      dogs. Other findings in hypothyroid dogs included an irregular surface to the
      thyroid capsule, a heterogeneous pattern to the thyroid parenchyma, and
      differences in the echogenic pattern between the left and right thyroid lobes.
      Results suggest that determination of thyroid size and volume by ultrasound may
      be a useful adjunctive test for differentiating between hypothyroid and euthyroid
      dogs with NTI.

PMID- 16095167
TI  - Experimental determination of net protein charge and A(tot) and K(a) of
      nonvolatile buffers in canine plasma.
AB  - Acid-base abnormalities frequently are present in sick dogs. The mechanism for an
      acid-base disturbance can be determined with the simplified strong ion approach,
      which requires accurate values for the total concentration of plasma nonvolatile
      buffers (A(tot)) and the effective dissociation constant for plasma weak acids
      (K(a)). The aims of this study were to experimentally determine A(tot) and K(a)
      values for canine plasma. Plasma was harvested from 10 healthy dogs; the
      concentrations of quantitatively important strong ions (Na+, K+, Ca2+, Mg2+, Cl-,
      L-lactate) and nonvolatile buffer ions (total protein, albumin, phosphate) were
      determined; and the plasma was tonometered with CO2 at 37 degrees C. Strong ion
      difference (SID) was calculated from the measured strong ion concentrations, and
      nonlinear regression was used to estimate values for A(tot) and K(a), which were
      validated with data from an in vitro and in vivo study. Mean (+/- SD) values for
      canine plasma were A(tot) = (17.4 +/- 8.6) mM (equivalent to 0.273 mmol/g of
      total protein or 0.469 mmol/g of albumin); K(a) = (0.17 +/- 0.11) x 10(-7); pK(a)
      = 7.77. The calculated SID for normal canine plasma (pH = 7.40; P(CO2) = 37 mm
      Hg; [total protein] = 64 g/L) was 27 mEq/L. The net protein charge for normal
      canine plasma was 0.25 mEq/g of total protein or 0.42 mEq/g of albumin.
      Application of the experimentally determined values for A(tot), K(a), and net
      protein charge should improve understanding of the mechanism for complex acid
      base disturbances in dogs.

PMID- 16095168
TI  - Dogs with heart diseases causing turbulent high-velocity blood flow have changes
      in platelet function and von Willebrand factor multimer distribution.
AB  - The purpose of this prospective study was to investigate platelet function using
      in vitro tests based on both high and low shear rates and von Willebrand factor
      (vWf) multimeric composition in dogs with cardiac disease and turbulent high
      velocity blood flow. Client-owned asymptomatic, untreated dogs were divided into
      4 groups: 14 Cavalier King Charles Spaniels (Cavaliers) with mitral valve
      prolapse (MVP) and no or minimal mitral regurgitation (MR), 17 Cavaliers with MVP
      and moderate to severe MR, 14 control dogs, and 10 dogs with subaortic stenosis
      (SAS). Clinical examinations and echocardiography were performed in all dogs.
      PFA100 closure times (the ability of platelets to occlude a hole in a membrane at
      high shear rates), platelet activation markers (plasma thromboxane B2
      concentration, platelet surface P-selectin expression), platelet aggregation (in
      whole blood and platelet-rich plasma with 3 different agonists), and vWf
      multimers were analyzed. Cavaliers with moderate to severe MR and dogs with SAS
      had longer closure times and a lower percentage of the largest vWf multimers than
      did controls. Maximal aggregation responses were unchanged in dogs with SAS but
      enhanced in Cavaliers with MVP (regardless of MR status) compared with control
      dogs. No significant difference in platelet activation markers was found among
      groups. The data suggest that a form of platelet dysfunction detected at high
      shear rates was present in dogs with MR and SAS, possibly associated with a
      qualitative vWf defect. Aggregation results suggest increased platelet reactivity
      in Cavaliers, but the platelets did not appear to circulate in a preactivated
      state in either disease.

PMID- 16095169
TI  - Effect of levothyroxine administration on hemostatic analytes in Doberman
      Pinschers with von Willebrand disease.
AB  - Levothyroxine administration has been suggested to be an effective treatment for
      canine von Willebrand disease (vWd), but evidence supporting this treatment is
      lacking. Effects of levothyroxine administration were evaluated in 8 euthyroid
      Doberman Pinschers with plasma von Willebrand factor (vWf) concentrations < 15%,
      characteristic of type 1 vWd. Levothyroxine (0.04 mg/kg PO q12h) and placebo were
      administered for 30 days in a 2-period, 2-treatment, double-blinded, crossover
      design with a 30-day washout period between treatments. Buccal mucosal bleeding
      time (BMBT), plasma vWf concentration (vWf: Ag), vWf collagen binding activity
      (vWf:CBA), factor VIII coagulant activity (FVIII:C), and serum concentrations of
      total thyroxine (T4), free thyroxine (fT4), 3,5,3'-triiodothyronine (T3), and
      thyroid-stimulating hormone (TSH) were measured on days 0, 2, and 30 of each
      treatment period. The 8 dogs (1 male, 7 females) had markedly low plasma vWf:Ag
      (mean, 8.9%; reference range, 70-180%) and vWf:CBA (mean, 11.1%; reference range,
      >70%). Response to placebo versus levothyroxine treatment was not significantly
      different between groups at day 0, 2, or 30 for BMBT, vWf:Ag, vWf:CBA, and
      FVIII:C. Serum T4, fT4, and T3 concentrations were significantly higher and serum
      TSH significantly lower in the levothyroxine-treated group than in the placebo
      group at days 2 and 30. Administration of levothyroxine at 0.04 mg/kg caused
      laboratory evidence of hyperthyroidism but did not affect plasma FVIII:C and
      vWf:Ag concentrations or vWf-dependent collagen binding and BMBT. The results of
      this study failed to identify a direct action of levothyroxine supplementation on
      plasma vWf concentration or activity in euthyroid Doberman Pinschers with vWd.

PMID- 16095170
TI  - Circulating concentrations of insulin-like growth factor-1 in dogs with naturally
      occurring mitral regurgitation.
AB  - Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth
      hormone, has effects on cardiac mass and function, and plays an important role in
      the regulation of vascular tone. In humans, an inverse relationship between
      degree of heart failure (HF) and circulating IGF-1 concentrations has been found
      in several studies. In dogs with HF, few studies have focused on IGF-1. We
      examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR)
      caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King
      Charles Spaniels (CKCSs) with a broad range of asymptomatic MR (median serum IGF
      1: 76.7 microg/L; 25-75 percentile, 59.8-104.9 microg/L). As expected, standard
      body weight and percentage under- or overweight correlated directly with IGF-1.
      MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28
      dogs with severe MR and stable, treated congestive HF had similar serum IGF-1
      concentrations (median, 100.8 g/L; 25-75 percentile, 74.9-156.5 microg/L) as 11
      control dogs (79.6 microg/L; 25-75 percentile, 64.1-187.4 microg/L; P = .84). In
      study 3, the plasma IGF-1 concentration of 15 untreated CKCSs with severe MR was
      16.4 +/- 24.2 microg/L lower (P = .02) at the examination when decompensated HF
      had developed (80.8 +/- 30.9 microg/L) than at a visit 1-12 months earlier (97.2
      +/- 39.8 microg/L), possibly in part due to an altered state of nutrition. The
      studies document that circulating IGF-1 concentrations are not altered before
      development of congestive HF in dogs with naturally occurring MR, but decrease by
      approximately 20% with the development of untreated HE In treated HF, circulating
      IGF-1 concentrations apparently return to within the reference range.

PMID- 16095171
TI  - Antioxidant status and biomarkers of oxidative stress in dogs with congestive
      heart failure.
AB  - Alterations in antioxidant status and oxidative stress have been documented in
      dogs with dilated cardiomyopathy (DCM). The purpose of this study was to more
      broadly assess this relationship in dogs with congestive heart failure (CHF).
      Malondialdehyde (MDA), 8-F(2alpha)-isoprostane, protein carbonyls, reduced (GSH)
      and oxidized (GSSG) glutathione, vitamins A, C, and E, and oxygen radical
      absorbance capacity (ORAC) were measured from a single venous blood sample from
      dogs with CHF secondary to DCM or chronic valvular disease (CVD) and in healthy
      controls. Nineteen dogs with CHF (14 CVD and 5 DCM) and 12 healthy controls were
      enrolled in the study. Concentrations of 8-F(2alpha)-isoprostane (CHF: 44.6 pg/mL
      [range, 27.1-98.0 pg/mL], controls: 25.3 pg/ mL [range, 11.1-80.4 pg/mL]) but not
      MDA (CHF: 4.11 microM [range, 1.89-6.39 microM], controls: 3.88 microM [range,
      2.14-4.72 microM]) or protein carbonyls (0.69 nmol/mg protein [range, 0.37-1.67
      nmol/mg protein], controls: 0.80 nmol/mg protein [range, 0.40-1.14 nmol/mg
      protein]) were significantly higher in the dogs with CHF than in the controls.
      Vitamin E concentration (CHF: 2,215 microg/ dL [range, 916-3,499 microg/dL],
      controls: 2,820 microg/dL [range, 1,738-3,775 microg/dL]) and GSH:GSSG (CHF: 12.0
      [range, 3.69-30.1], controls: 22.7 [range, 12.5-227]) were significantly lower,
      whereas ORAC (CHF: 824 micromol Trolox equivalent/L [range, 304-984], controls:
      497 micromol Trolox equivalent/L [range, 258-759]) and vitamin C (CHF: 0.90 mg/dL
      [range, 0.55-2.02 mg/dL], controls: 0.72 mg/dL [range, 0.43-0.85 mg/dL])
      concentrations were higher in dogs with CHF than in controls. Vitamin A
      concentrations were not different between dogs with CHF and controls. No
      differences in any of the parameters were detected between dogs with DCM versus
      those with CVD. Some antioxidant defenses are decreased in dogs with CHF, and
      some biomarkers of oxidative stress are increased in dogs with CHF. The effect of
      dietary interventions to correct this imbalance in antioxidant defenses warrants
      further study.

PMID- 16095172
TI  - Quantitative echocardiographic [corrected] evaluation of mitral endocardiosis in
      dogs using ratio indices.
AB  - This study compares M-mode echocardiographic ratio indices (ERIs) in dogs with
      mitral regurgitation due to chronic valvular disease (CVD/MR) for their ability
      to discriminate and quantify associated echocardiographic changes. Weight-based M
      mode ERIs were determined retrospectively for 2 groups of dogs, normal (n = 47)
      and CVD/MR (n = 176). The CVD/MR group was further subdivided into those with
      (CVD/MR B, n = 74) and without (CVD/MR A, n = 102) left-sided congestive heart
      failure (LCHF). ERIs were compared descriptively (summary statistics) and also by
      receiver-operator characteristic curve areas (ROCAs) for their ability to
      discriminate between groups. Univariate logistic regression (LR) models were used
      to estimate the odds ratio for each ERI as a predictor of the CVD/MR condition as
      well as to predict LCHF within the CVD/MR group. A novel ERI (wdeltaA), designed
      to express body size-normalized short-axis stroke area, was sensitive (90%) and
      specific (98%) to discriminate between normal and CVD/MR at a cutoff value of 1.8
      standard deviations (wdeltaA = 2.1). Prediction of LCHF within the CVD/MR group
      was more problematic, but an ERI expressing left atrial size (wLA) showed 76%
      sensitivity and 81% specificity at a cutoff value of 5.2 standard deviations (wLA
      = 1.55). Ours was a descriptive study of echocardiographic patterns of pathology
      associated with CVD/ MR and determined which ERIs are sensitive and specific for
      CVD/MR and for LCHE ERIs normalize echocardiographic data for body size in dogs
      and are well-suited to quantitative descriptions and analysis.

PMID- 16095173
TI  - Polymerase chain reaction screening for DNA viruses in paraffin-embedded brains
      from dogs with necrotizing meningoencephalitis, necrotizing leukoencephalitis,
      and granulomatous meningoencephalitis.
AB  - The objective of this investigation was to determine whether or not herpesvirus
      (herpes-), adenovirus (adeno-), or canine parvovirus DNA is present in the brains
      of dogs with necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis
      (NLE), and granulomatous meningoencephalitis (GME). Paraffin-embedded brain
      specimens from 12 histopathologically confirmed dogs with NME, 3 with NLE, and 7
      with GME were screened for viral DNA with degenerate herpes- and adenovirus
      polymerase chain reaction (PCR) and a canine parvovirus-specific PCR. Positive
      control specimens included genomic viral DNA and paraffin-embedded tissues from
      dogs with confirmed herpes-, adeno-, or canine parvovirus infections. Herpes-,
      adeno-, or canine parvovirus DNA was amplified by PCR from the corresponding
      positive-control specimens. Negative controls included 7 dogs with various brain
      disorders and produced no viral amplicons. The 22 dogs with NME, NLE, and GME
      were negative for viral DNA. Additional studies testing for other viruses or
      inherited genetic mutations are warranted to gain insight into the etiologies of
      NME, NLE, and GME. We discuss potential etiologies and provide a clinical and
      histopathologic overview of these common canine encephalitides.

PMID- 16095174
TI  - Association between ovarihysterectomy and feline mammary carcinoma.
AB  - The etiopathogenesis of feline mammary carcinoma is not well understood. Although
      putative, risk factors include breed, reproductive status, and regular exposure
      to progestins. An association between age at ovarihysterectomy (OHE) and mammary
      carcinoma development has not been established. Therefore, a case-control study
      was performed to determine the effects of OHE age, breed, progestin exposure, and
      parity on feline mammary carcinoma development. Cases were female cats diagnosed
      with mammary carcinoma by histological examination of mammary tissue. Controls
      were female cats not diagnosed with mammary tumors selected from the same biopsy
      service population. Controls were frequency matched to cases by age and year of
      diagnosis. Questionnaires were sent to veterinarians for 308 cases and 400
      controls. The overall questionnaire response rate was 58%. Intact cats were
      significantly overrepresented (odds ratio [OR] 2.7, confidence interval [CI] =
      1.4-5.3, P < .001) in the mammary carcinoma population. Cats spayed prior to 6
      months of age had a 91% reduction in the risk of mammary carcinoma development
      compared with intact cats (OR 0.9, CI = 0.03-0.24). Those spayed prior to 1 year
      had an 86% reduction in risk (OR 0.14, CI = 0.06-0.34). Parity did not affect
      feline mammary carcinoma development, and too few cats had progestin exposure to
      determine association with mammary carcinoma. Results indicate that cats spayed
      before 1 year of age are at significantly decreased risk of feline mammary
      carcinoma development.

PMID- 16095175
TI  - Hemangiosarcoma in 11 young horses.
AB  - Hemangiosarcoma is a rare neoplasm of horses and hemangiosarcoma in young horses
      might behave differently than in mature horses. The purpose of this study was to
      identify the characteristics of hemangiosarcoma occurring in horses < or = 3
      years of age. Medical records from 1982 to 2004 were searched for horses < or = 3
      years of age with a histopathologic diagnosis of hemangiosarcoma. Eleven records
      were identified. Thoroughbred and Thoroughbred crosses predominated. Age ranged
      from 9 days to 3 years. All horses presented with cutaneous or leg swellings or
      joint effusion. Physical examination findings included tachycardia, fever, and
      depression. Laboratory abnormalities included anemia (5/11), hyperfibrinogenemia
      (4/11), hypofibrinogenemia (3/11), thrombocytopenia (2/11), and neutrophilic
      leukocytosis (1/11). Ultrasonographic and radiographic evaluation was not
      diagnostic in any case. Antemortem histopathologic diagnosis was obtained in 10
      cases. Six of 11 horses were euthanized. Surgical resection was performed in 5
      horses, 2 of which were later euthanized. Diagnosis was confirmed histologically
      at postmortem examination in all euthanized horses. Two cases resolved
      spontaneously. Early histopathologic diagnosis may allow cure if the mass is
      localized and amenable to surgical resection. In cases where the horse is
      medically stable, and masses are not interfering with quality of life, a period
      of observation may be warranted.

PMID- 16095176
TI  - Accuracy of indirect measurement of blood pressure in neonatal foals.
AB  - The objectives of this study were to assess, in anesthetized neonatal foals, the
      accuracy of 2 automated indirect oscillometric monitors for measurement of mean
      arterial pressure (MAP), to determine the optimal site of cuff placement for MAP
      monitoring, and to determine the relationship between arterial blood pressure and
      cardiac output. Ten neonatal foals were anesthetized and instrumented with a
      catheter in the metatarsal artery for direct MAP monitoring and measurement of
      cardiac output by lithium dilution. Concurrent MAP measurements were obtained
      with Cardell and Dinamap oscillometric monitors with cuffs placed at 3 different
      sites (coccygeal, metatarsal, and median arteries). Blood pressure was
      manipulated by varying the depth of anesthesia and by administration of
      dobutamine or phenylephrine. A statistically significant (P = .025) interaction
      was found between the type of monitor and cuff placement site. With the Cardell
      monitor, placement of the cuff over the coccygeal artery resulted in a
      significantly lower bias than placement over the median or dorsal metatarsal
      artery (P < .0001 and P = .0149, respectively). No significant difference in bias
      was found with cuff placement site when using the Dinamap monitor. The
      correlation coefficient (r) between MAP and cardiac output was 0.47. Indirect
      oscillometry with a cuff placed over the coccygeal artery or dorsal metatarsal
      artery is an acceptable method for measuring MAP in foals. Blood pressure does
      not correlate well with cardiac output in anesthetized foals.

PMID- 16095177
TI  - Biochemical markers of cardiac injury in normal, surviving septic, or
      nonsurviving septic neonatal foals.
AB  - The cardiac biomarkers cardiac troponin T (cTnT) and I (cTnI) and the cardiac
      isoenzyme of creatine kinase (CKMB) are used extensively in human medicine to
      diagnose and provide valuable prognostic information in patients with ischemic,
      traumatic, and septic myocardial injury. We designed a study to establish normal
      values for these markers in healthy, neonatal foals and to compare them with
      values obtained from septic neonates in a referral hospital population. The 25th,
      50th, 75th, and 95th percentiles for cTnI and CKMB in the healthy-foal population
      were 0.08, 0.14, 0.25, 0.49 ng/mL and 1.4, 2.3, 4.0, 7.4 ng/mL, respectively. The
      values obtained for cTnT were frequently (43/52 foals; 83%) below the lower limit
      of detection of the assay (0.009 ng/mL), but the median and range were 0.009 and
      0.009-0.041 ng/mL, respectively. In the septic foal population, the 25th, 50th,
      75th, and 95th percentile values for cTnI and CKMB were 0.05, 0.12, 0.22, and
      1.10 ng/mL and 2.0, 4.4, 7.8, and 24 ng/mL, respectively. The values obtained for
      cTnT were less frequently below the lower limit of detection (23/38 foals; 60%)
      compared with the healthy foal population, and the median and range were 0.009
      and 0.009-0.20 ng/mL, respectively. Significantly higher values were observed for
      cTnT and CKMB in septic foals compared with the healthy neonatal foal population,
      but there were no differences among septic foals in survivors compared with
      nonsurvivors. These findings suggest that myocardial injury occurs during
      septicemia in neonatal foals but that the injury is not associated with survival
      among septic foals.

PMID- 16095178
TI  - Use of a quantitative strong ion approach to determine the mechanism for acid
      base abnormalities in sick calves with or without diarrhea.
AB  - Acid-base abnormalities are frequently present in sick calves. The mechanism for
      an acid-base disturbance can be characterized using the strong ion approach,
      which requires accurate values for the total concentration of plasma nonvolatile
      buffers (A(tot)) and the effective dissociation constant for plasma weak acids
      (K(a)). The aims of this study were to experimentally determine A(tot), K(a), and
      net protein charge values for calf plasma and to apply these values
      quantitatively to data from sick calves to determine underlying mechanisms for
      the observed acid-base disturbance. Plasma was harvested from 9 healthy Holstein
      Friesian calves and concentrations of quantitatively important strong ions (Na+,
      K+, Ca2+, Mg2+, Cl-, L-lactate) and nonvolatile buffer ions (total protein,
      albumin, phosphate) were determined. Plasma was tonometered with CO2 at 37
      degrees C, and plasma P(CO2) and pH measured over a range of 15-159 mm Hg and
      6.93-7.79, respectively. Strong ion difference (SID) was calculated from the
      measured strong ion concentrations, and nonlinear regression was used to estimate
      values for A(tot) and K(a) from the measured pH and P(CO2) and calculated SID.
      The estimated A(tot) and K(a) values were then validated using data from 2 in
      vivo studies. Mean (+/- SD) values for calf plasma were A(tot) = 0.343 mmol/g of
      total protein or 0.622 mmol/g of albumin; K(a) = (0.84 +/- 0.41) x 10(-7); pK(a)
      = 7.08. The net protein charge of calf plasma was 10.5 mEq/L, equivalent to 0.19
      mEq/g of total protein or 0.34 mEq/g of albumin. Application of the strong ion
      approach to acid-base disturbances in 231 sick calves with or without diarrhea
      indicated that acidemia was due predominantly to a strong ion acidosis in
      response to hyponatremia accompanied by normochloremia or hyperchloremia and the
      presence of unidentified strong anions. These results confirm current
      recommendations that treatment of acidemia in sick calves with or without
      diarrhea should focus on intravenous or PO administration of a fluid containing
      sodium and a high effective SID.

PMID- 16095179
TI  - Efficacy of azithromycin dihydrate in treatment of cryptosporidiosis in naturally
      infected dairy calves.
AB  - The objective of this study was to evaluate the therapeutic efficacy of
      azithromycin treatment of cryptosporidiosis in naturally infected calves under
      field conditions. Fifty Holstein calves with cryptosporidiosis infection were
      divided into 5 groups: 1 group (10 calves) was unmedicated and served as the
      control group and was given distilled water only, whereas the other groups (10
      animals per group) were medicated orally with azithromycin at the doses of 500
      (group 1), 1,000 (group 2), 1,500 (group 3), and 2,000 mg (group 4) PO once daily
      for 7 days. The animals were examined clinically and fecal samples were collected
      on the 1st (inclusion day), 7th, 14th, and 21st days of the study. Drug efficacy
      was assessed by evaluating diarrhea, oocyst shedding, and weight gains from days
      1 to 21 (4 assessments). Significant differences were observed in reductions of
      oocyst shedding (P < .05) and the fecal diarrhea incidence (P < .05) in groups 3
      and 4 when compared with groups 1 and 2 and the control group. Weight gain of
      medicated calves was significantly higher than that of the unmedicated calves
      throughout the study (P < .05). The drug significantly suppressed oocyst shedding
      and resulted in significant improvements in clinical signs. Therefore, this
      suppression may have significant effect on the reduction of environmental
      contamination by cryptosporidial oocysts. From the economic point view, authors
      suggest that the most effective dose of azithromycin for the treatment of
      cryptosporidiosis in calves should be at 1,500 mg/d for 7 days.

PMID- 16095180
TI  - Endothelin-1 concentrations in clone calves, their surrogate dams, and fetal
      fluids at birth: association with oxygen treatment.
AB  - Increased endothelin-1 (ET-1) plasma concentration in human infants is associated
      with persistent pulmonary hypertension of the newborn, a problem also identified
      in calves derived from somatic cell clone technology. Increased ET-1 also is
      present in the amnionic fluid and plasma of the infant and mother in
      preeclampsia, a condition associated with abnormal placentation. Abnormalities in
      placentation are identified in clone calves. We measured ET-1 in fetal fluid,
      calf plasma, and surrogate dam plasma in 40 clone calves at the time of term
      delivery. Calves were subsequently identified as being either oxygen treated (O2)
      or non-oxygen treated based on their postpartum clinical course. Fetal fluid ET-1
      concentration greater than 1.4 ng/mL carried a 3-fold increase in odds of the
      calf being treated with oxygen. Maternal plasma ET-1 concentration was greater in
      the O2 group (13 pg/ mL: [8-23 pg/mL] versus 25 pg/mL [12-40 pg/mL]; median, 25
      75 percentile). Plasma ET-1 concentration in calves was not significantly
      different between groups. Fetal fluid ET-1 may serve as a marker for neonatal
      disorders of oxygenation in clone calves and the source of ET-1 may be the
      placenta.

PMID- 16095181
TI  - Kentucky Coffee Tree intoxication in a dog with cerebellovestibular signs,
      bradycardia, hypotension, and hypoglycemia.

PMID- 16095182
TI  - Giant unruptured aneurysm of the left sinus of Valsalva in the left ventricular
      outflow tract of a young dog.

PMID- 16095183
TI  - Primary orthostatic tremor in Great Danes.

PMID- 16095184
TI  - Perianal malignant melanoma in a dog.

PMID- 16095185
TI  - Insulin-like growth factors and recurrent hypoglycemia associated with renal cell
      carcinoma in a horse.

PMID- 16095186
TI  - Antimicrobial drug use in veterinary medicine.
AB  - Recognizing the importance of antimicrobial resistance and the need for
      veterinarians to aid in efforts for maintaining the usefulness of antimicrobial
      drugs in animals and humans, the Board of Regents of the American College of
      Veterinary Internal Medicine charged a special committee with responsibility for
      drafting this position statement regarding antimicrobial drug use in veterinary
      medicine. The Committee believes that veterinarians are obligated to balance the
      well-being of animals under their care with the protection of other animals and
      public health. Therefore, if an animal's medical condition can be reasonably
      expected to improve as a result of treatment with antimicrobial drugs, and the
      animal is under a veterinarian's care with an appropriate veterinarian-client
      patient relationship, veterinarians have an obligation to offer antimicrobial
      treatment as a therapeutic option. Veterinarians also have an obligation to
      actively promote disease prevention efforts, to treat as conservatively as
      possible, and to explain the potential consequences associated with antimicrobial
      treatment to animal owners and managers, including the possibility of promoting
      selection of resistant bacteria. However, the consequences of losing usefulness
      of an antimicrobial drug that is used as a last resort in humans or animals with
      resistant bacterial infections might be unacceptable from a public or population
      health perspective. Veterinarians could therefore face the difficult choice of
      treating animals with a drug that is less likely to be successful, possibly
      resulting in prolonged or exacerbated morbidity, to protect the good of society.
      The Committee recommends that voluntary actions be taken by the veterinary
      profession to promote conservative use of antimicrobial drugs to minimize the
      potential adverse effects on animal or human health. The veterinary profession
      must work to educate all veterinarians about issues related to conservative
      antimicrobial drug use and antimicrobial resistance so that each individual is
      better able to balance ethical obligations regarding the perceived benefit to
      their patients versus the perceived risk to public health. Specific means by
      which the veterinary profession can promote stewardship of this valuable resource
      are presented and discussed in this document.

PMID- 16095187
TI  - [Informatics in the Croatian health care system].
AB  - Informatization process of the Croatian health care system started relatively
      early. Computer processing of data of persons not covered by health insurance
      started in 1968 in Zagreb. Remetinec Health Center served as a model of computer
      data processing (CDP) in primary health care and Sveti Duh General Hospital in
      inpatient CDP, whereas hospital administration and health service were first
      introduced to Zagreb University Hospital Center and Sestre Milosrdnice University
      Hospital. At Varazdin Medical Center CDP for health care services started in
      1970. Several registries of chronic diseases have been established: cancer,
      psychosis, alcoholism, and hospital registries as well as pilot registries of
      lung tuberculosis patients and diabetics. Health statistics reports on healthcare
      services, work accidents and sick-leaves as well as on hospital mortality started
      to be produced by CDP in 1977. Besides alphanumeric data, the modern information
      technology (IT) can give digital images and signals. Communication in health care
      system demands a standardized format of all information, especially for
      telemedicine. In 2000, Technical Committee for Standardization in Medical
      Informatics was founded in Croatia, in order to monitor the activities of the
      International Standardization Organization (ISO) and Comite Europeen de
      Normalisation (CEN), and to implement their international standards in the
      Croatian standardization procedure. The HL7 Croatia has also been founded to
      monitor developments in the communication standard HL7. So far, the Republic of
      Croatia has a number of acts regulating informatization in general and
      consequently the informatization of the health care system (Act on Personal Data
      Confidentiality, Act on Digital Signature, Act of Standardization) enacted. The
      ethical aspect of data security and data protection has been covered by the Code
      of Ethics for medical informaticians. It has been established by the
      International Medical Informatics Association (IMIA), and the Croatian Society of
      Medical Informatics (CSMI) has translated it into Croatian and published it on
      its website. Based on a survey of medical staff attitudes toward health care
      system informatization, the Croatian health system appears to be ready for
      informatization. The only requirement is that the present and future health care
      providers have appropriate medical informatics education, proper computer
      equipment at their workplace, and an opportunity to participate in the
      development and/or improvement of the health information system. One of the EU
      health strategy priorities is the improvement of health information and
      knowledge. It means that integrated health information systems are required, i.e.
      systems able to provide key information on health and health care system to the
      politicians, health professionals and public in general.

PMID- 16095188
TI  - [Virtual polyclinic--consultant health service for rural areas and islands].
AB  - The development of medical sciences and digital revolution in health care have
      made possible the creation of new models for hospital care and primary health
      care. Health care management usually does not follow all possible solutions of
      new computer technology. Croatian health system is based on large hospital
      centers in the mainland and small, poorly equipped remote medical units. The
      possibility of sharing medical information using telematic technologies brings
      all knowledge of the large, powerful hospital centers close to remote medical
      units. Working in a small, remote consultation office on the island Cres, the
      author A. M. became part of medical periphery far from the security of hospital
      on the mainland. After five years of the work on telemedicine projects for the
      islands, we have introduced a new medical practice concept of communication
      between remote medical units and clinical hospital centers in the mainland. The
      pilot project Virtual Polyclinic-Medical Consultation System for the Islands and
      Remote Areas is a good example of the possible new models in health care
      structure. Our experience indicates that organization of health care in remote
      areas depends not only on advanced technical solutions but also on team work and
      medical professionals.

PMID- 16095189
TI  - [Introducing computer units into the reception office as part of the Vrapce
      Psychiatric Hospital Information System].
AB  - Computerized medical record has become a necessity today, because of both the
      amount of present-day medical data and the need of better handling and processing
      them. In more than 120 years of the Vrapce Psychiatric Hospital existence, the
      most important changes in the working concept of the reception office took place
      when computer technology was introduced into the routine use. The reception
      office of the Hospital is the vital place where administrative activities
      intersect with medical care for a patient presenting to the Hospital. The
      importance of this segment of the Hospital is emphasized by the fact that the
      reception office is in function and at patients' disposition round-the-clock, for
      365 days a year, with great frequency of patients. The shift from the established
      way of registering medical data on patient admission in handwriting or, later,
      typescript, to computer recording was a challenging and demanding task (from the
      aspects of hardware, software, network, education) for the development team as
      well as for the physicians because it has changed the concept (logic of the
      working process) of previous way of collecting the data from the patient
      (history, status, diagnostic procedures, therapy, etc.). The success in the
      development and implementation of this project and the confirmation of its
      usefulness during the four-year practice at Vrapce Psychiatric Hospital are best
      illustrated by the fact that other psychiatric hospitals in Croatia have already
      introduced or are introducing it in their daily practice.

PMID- 16095190
TI  - [CroDiab NET--electronic diabetes registry].
AB  - INTRODUCTION AND AIM: National diabetes registry has been an important aim of
      Croatian diabetology for a long time. Currently, efforts are made to define a
      national registry based upon Cro Diab NET, a computer software designed as a
      patient record form and suitable for automatic extraction of data for the
      registry. METHODS: Diagnostic entities captured are defined by the International
      Classification of Diseases and Related Health Problems, 10th rev. (E10--E14,
      G63.2, and H36) and ICF (b540, b279, b298, b2108). Central CroDiabNET module is
      BIS (Basic Informatic Sheet), recognized by the international diabetology
      community as optimal data collection form for the follow-up and improvement of
      diabetes care. There are several ways of data collection: secondary and tertiary
      health centers with diabetes care within their scope of activities send BIS on
      their patients to the central base by a modem, other secondary and tertiary
      health centers as well as primary health care will send data on their diabetic
      patients either via the Internet or by mail (interactive BIS will be available on
      the registry www page). The preferred method of data collection is the electronic
      one. The central base automatically links records of uniquely identified
      patients. Other records are checked separately, compared with the existing
      records and linked manually. Data confidentiality is ensured by double password
      protection of excess at the level of both users and registry. Unauthorised access
      is highly unlikely. RESULTS: So far, most of the secondary and tertiary health
      centers dealing with diabetology have been active in data collection. Inclusion
      of primary care (family physicians) is in progress. The last report covered data
      from 13 centers. Besides data on the number of patients, the reports contained
      analyses of BIS patient data availability. This is a tool for the analysis of the
      quality of registry and it can also provide basic data for planned actions aimed
      at quality of care improvement. Regular data collection from all levels of health
      care with concomitant connection of the registry to the national death registry
      started in 2004. With complete implementation of these processes a unique
      national diabetes database will be defined. CONCLUSION: Results of the use of
      CroDiabNET so far confirm its potency as a valuable tool for population registry
      of diabetes as well as for improvement of diabetes health care. Regular periodic
      reports reveal an increasing number of centers involved. With continuation of
      this trend the registry will become a national, population-based database.

PMID- 16095191
TI  - [Founding and development of the Croatian Health Information System].
AB  - Information systems, either computer or paper based, are the key to business
      effectiveness and efficiency of healthcare organizations. The rationale of
      starting a large healthcare informatics project by the Ministry of Health and
      Welfare may be argued by two needs: (1) the need of medical data transformation
      into the information required for public health policy decision-making; and (2)
      measures in the field of health and pharmacoeconomics, i.e. systematic
      surveillance of healthcare costs that define the prospects for savings without
      lowering the level of service (estimated at 20%-30% of potential savings), along
      with the need of transparency and adoption of European Union directives and
      standards. Implementation of the proposed system results in two groups of
      fundamental functions: (1) the creation of a central public health information
      system which facilitates real-time tracking of primary healthcare cost
      generators, which in turn are used for creating health economics policy, and (2)
      to automatize the process of generating a consolidated national health budget
      including the Croatian Institute of Health Insurance and hospitals as well as
      consolidated financial reports for all those involved in the healthcare system.
      The model of the National Health Information System of the Republic of Croatia is
      described.

PMID- 16095192
TI  - [Role of standardization in health care system computerization].
AB  - Standardization system includes development, publishing and promotion of
      standards, as well as their use in practice. Products, services and processes in
      a variety of human activities should be standardized. The goal of standardization
      is to achieve a high security level, a high quality, usefulness and effectiveness
      as well as limitation of variability, ensuring compatibility and replacement (of
      products), and to eliminate technical problems in the international exchange of
      people, work, products and services. The leading areas/objects of standardization
      in medical informatics are electronic health record, classification in health
      care, communication and message exchange as well as data security and protection
      of the whole health information system. Technical Committee for Standardization
      in Medical Informatics (TC215) has so far accepted fifteen standards and
      prestandards. The affiliate HL7 Croatia works on localization of communication
      standard HL7 and adaptation to the Croatian requirements.

PMID- 16095193
TI  - [Information system in primary health care].
AB  - The Croatian Ministry of Health started a health care system computerization
      project aimed at strengthening the collaboration among health care institutions,
      expert groups and individual health care providers. A tender for informatic
      system for Primary Health Care (PHC) general practice, pediatrics and gynecology,
      a vital prerequisite for project realization, has now been closed. Some important
      reasons for undertaking the project include rationalization of drug utilization,
      savings through a reduced use of specialists, consultants and hospitalization,
      then achievement of better cooperation, work distribution, result linking, data
      quality improvement (by standardization), and ensuring proper information-based
      decision making. Keeping non-standardized and thus difficult to process data
      takes too much time of the PHC team time. Since, however, a vast amount of data
      are collected on only a few indicators, some important information may remain
      uncovered. Although decisions made by health authorities should rely on evidence
      and processed information, the authorities spend most of the time working with
      raw data from which their decisions ultimately derive. The Informatic Technology
      (IT) in PHC is expected to enable a different approach. PHC teams should be
      relieved from the tedious task of data gathering and the authorities enabled to
      work with the information rather than data. The Informatics Communication
      Technology (ICT) system consists of three parts: hardware (5000 personal
      computers for work over the Internet), operative system with basic software
      (editor, etc.), and PHC software for PHC teams. At the national level (National
      Public Health Informatics System), a software platform will be built for data
      collection, analysis and distribution. This data collection will be based on the
      International Classification of Primary Care (ICPC-2) standard to ensure the
      utilization of medical records and quality assessment. The system permits bi
      directional data exchange between a central database and sources at different
      levels, across the spectrum from basic PHC teams to local authorities. This will
      enable data collection control, comparisons with national averages and prompt
      distribution of information over the Internet. The investment into IT is a
      strategic imperative having no alternative. A cost/benefit analysis has shown its
      operation in the PHC system to return the investment in two years. As defined
      according to the Project priorities (with measurable objectives), the use of new
      technologies will be introduced by stages.

PMID- 16095194
TI  - [Development of information system at Sestre Milosrdnice Clinical Hospital].
AB  - Information Systems (IS) in healthcare are complex with a heterogeneous
      structure. They support decision making in healthcare and therefore must be
      integrated, consistent, reliable, secure and simple for use and maintenance. Data
      entry is strongly controlled, data are coded and ready for inventory printing or
      scientific analysis. Efforts in developing the Integrated Hospital Information
      System (IHIS) at Sestre Milosrdnice University Hospital, Zagreb (Croatia) from a
      Hospital Information System (HIS) are presented. From the very beginning, the
      Information System was developed without planning, only to satisfy the current
      needs and to stay within financial possibilities. Today, many hospital
      departments have their own Information Subsystems and one or two servers. All
      local area networks and offline computers are connected to optical ring and
      through the farm of servers (firewall, www, e-mail, DNS-Domain Name System) to
      the Internet. We need a long time to achieve the current degree of development of
      IS. However, today we can obviously recognize a few layers of information
      applications just like business application, medicine application, scientific
      application, education application, telemedicine and Internet application. Very
      powerful information technology and very fast progress in communications leads to
      digital or paperless hospital.

PMID- 16095195
TI  - [Implementation of integrated hospital information system in the existing
      hospital organization--experience at Dubrava Clinical Hospital in Zagreb].
AB  - In the modern hospital information systems govern extremely important functions
      such as patient management, control of work flows, administration, etc., with a
      great variety of recommended standards used in functional integration of
      healthcare information systems. The main parts of the original idea of the
      integrated Hospital Information System have been implemented at Dubrava
      University Hospital in Zagreb through several phases, resulting in data
      production covering distinct areas of hospital administration. This paper
      describes the basic idea of information, organization problems and steps taken in
      the implementation. International standards in communication have been
      implemented in the system.

PMID- 16095196
TI  - [Hospital information system--project of implementation of SAP information system
      at Sveti Duh General Hospital].
AB  - Nowadays, as medical and hospital institutions have been facing a growing need of
      a more efficient provision of healthcare services to patients, with simultaneous
      complete monitoring of the successfulness of business activities, integrated
      information systems appear as the logical choice for the support to hospital
      business processes. The integrated business information system implemented at
      Sveti Duh General Hospital is a comprehensive system that supports all hospital,
      clinical and administrative processes, while providing the basis for decision
      making regarding the patients and hospital management. The system also enables
      transfer of all data with specific medical business segments such as laboratory
      device management. The project for the implementation of the information system
      was realized in accordance with the requests from the Ministry of Health,
      applying the proven methodology for the execution of such complex projects. The
      project team consisted of a number of consultants from b4b Co. from Zagreb, as
      well as Hospital employees. The new information system is completely ready for
      going live; however, the necessary decisions have to be made first. The
      application of the system gives the medical staff more time for their
      professional work with patients, and through longterm collection and analysis of
      data on symptoms, illnesses and medical treatments, the information system
      becomes an important tool for the improvement of health and quality of healthcare
      system in general.

PMID- 16095197
TI  - [Development of laboratory information system--quality standards].
AB  - The aim of the study was to determine structural modules of laboratory
      information system (LIS) for the application of new biomedical and information
      technologies by utilizing current organizational trends. The method used included
      definition of structural modules according to significant LIS properties, e.g., a
      large number of data, automation of analyses and rapid exchange of information,
      and according to the process of information establishment the collection,
      organization, selection, synthesis and distribution. Thus, outdated distributed
      software at the Clinical Institute of Laboratory Diagnosis has now been replaced
      by modular organization. Modules have been developed for the following: data
      input, online operation of laboratory instruments, preparation of results,
      compilation of medical documentation on quality assurance based on the
      application of quality standards, management of finances, and for point of care
      testing. The method of re-engineering as well as adherence to EN and ISO quality
      standards were utilized in planning the development of LIS based on the
      application of new information technologies and in shaping business processes.
      The application of re-engineering in LIS development results in quality
      improvement, reduces the cost and time necessary for performance of procedures,
      and improves relations in organizational structure.

PMID- 16095198
TI  - [Register of treated psychoactive drug addicts].
AB  - In the order to accomplish data collection for the Treated Psychoactive Drug
      Addicts Registry, the Drug Abuse Registration Program has been developed
      according to the adapted Council of Europe Pompidou group questionnaire. The main
      goals of the system are: introduction of a local database, implementation of
      standard data consistency control algorithm, personal data protection and
      connection to public health network. Paper forms are being gradually discarded.
      The procedure of registration proposed will improve data quality, increase
      promptness of data entry, and enable feedback from the central registry toward
      registration institutions. The introduction of the system will gradually modify
      the operation while strictly respecting personal data confidentiality.

PMID- 16095199
TI  - [National public health information system].
AB  - Information production and its communication being a key public health activity,
      developing modern information systems is a precondition for its fulfilling these
      assignments. A national public health information system (NPHIS) is a set of
      human resources combined with computing and communication technologies. It
      enables data linkage and data coverage as well as undertaking information
      production and dissemination in an effective, standardized and safe way. The
      Croatian Institute of Public Health LAN/WAN modules are under development. Health
      Safety System, Health Workers Registry, and Digital Library are among the
      Institute's developmental priorities. Communication between NPHIS participants
      would unfold over the Internet by using every relevant data protection method.
      Web technology-based applications would be run on special servers. Between
      individual applications, use would be made of the transaction module of
      communication through an exchange of the HL7 standard-based xml messages. In the
      conditions of transition, the health system must make an optimal use of the
      resources, which is not feasible without applying modern information and
      communication technologies.

PMID- 16095200
TI  - [Computerization and the importance of information in health system, as in health
      care resources registry].
AB  - The possibilities of creating a health care resources registry and its operating
      in Croatia as well as the importance of information in health system are
      described. At the Croatian Institute of Public Health, monitoring of human
      resources is performed through the national Health Workers Registry. It also
      covers basic data on all health units, bed capacities of health facilities
      included. The initiated health care computerization has urged the idea of forming
      one more database on physical resources, i.e. on registered medical devices and
      equipment, more complete. Linking these databases on health resources would
      produce a single Health Care Resources Registry. The concept views Health Care
      Resources Registry as part of the overall health information system with
      centralized information on the health system. The planned development of segments
      of a single health information system is based on the implementation of the
      accepted international standards and common network services. Network services
      that are based on verified Internet technologies are used within a safe, reliable
      and closed health computer network, which makes up the health intranet (WAN--Wide
      Area Network). The resource registry is a software solution based on the
      relational database that monitors history, thus permitting the data collected
      over a longer period to be analyzed. Such a solution assumes the existence of a
      directory service, which would replace the current independent software for the
      Health Workers Registry. In the Health Care Resources Registry, the basic data
      set encompasses data objects and attributes from the directory service. The
      directory service is compatible with the LDAP protocol (Lightweight Directory
      Access Protocol), providing services uniformly to the current records on human
      and physical resources. Through the storage of attributes defined according to
      the HL7 (Health Level Seven) standard, directory service is accessible to all
      applications of the health information system. Directory service does not follow
      the history of attribute changes, and is optimized for a large number of
      authorizing inquiries. With it, one follows the following objects and attributes:
      persons, groups of people (patients, physicians, other personnel), roles (right
      of access and administrator permissions), organizational units, unit locations,
      devices and services (according to the list of services and procedures). One can
      add to the Health Care Resource Registry such attributes as are nonessential for
      inclusion in the directory service, but are of public health value.
      Authentication, authorization and digital signature are done by means of Smart
      Cards, which are used as protective elements against access to system functions,
      and simultaneously as a physical medium for the storage of the official
      certificate with which documents are signed digitally. As FINA (state financial
      control agency) has completed a system for certificate issuance and verification,
      the option of official digital signature is also available as a computer network
      service. Any changes taking place in the directory service are transferred by XML
      messages to a separate part of the Registry that reads them and automatically
      modifies records in the relational database. Because data input and data changes
      are made in health units, this makes the data updated and directly connected with
      health working operations. This avoids all one-time data collection campaigns
      using form filling about the devices and equipment in the future. As it is very
      difficult to monitor from a central standpoint how accurate and update the
      information is, it is necessary to delegate the permissions and duties associated
      with making changes to the directory service. By this organizational setup, the
      time needed to ensure data quality control is reduced. In the case described, the
      Health Care Resource Registry becomes an indicator of change, acquiring certain
      characteristics of an analytical system. An analysis of topical data renders
      possible proactive action and makes more effective the planning and utilization
      of available resources. Providing answers on the current data quickly could also
      be important to solution-seeking in emergencies. The present proposal to
      establish the Registry is intended to facilitate the future process of planning
      and striking a balance between investments in human and physical resources. For
      health expenditure control, having reliable information related to the use and
      purchase of new medical technology is particularly important. World Health
      Organization and European Union have also emphasized the need to develop new
      indicators in this area.

PMID- 16095201
TI  - [Informatics system at the Croatian Institute of Health Insurance today and plans
      for future].
AB  - Basic information is provided on the informatics system at the Croatian Institute
      of Health Insurance (CIHI). The focus is on the newwork infrastructure, which
      connects 130 locations 24 hours on line and installed hardware and software
      equipment at CIHI. A modern network infrastructure makes technical basis of
      modern informatics system. Technical data on the safe and reliable communication
      system with FR telecommunication capacity are presented. UNIX servers at the
      headquaters and branch offices, INFORMIX database and the own application ZOROH
      provide a basis for core business. Active Directory, web pages www.hzzo-net.hr,
      Intranet and CIHI IT portal are the main parts of the modern CIHI office info
      subsystem. Basic information is given about the system for production
      and.distribution of health insurance cards--plastic cards with magnetic strip for
      basic and additional health insurance. Informatics Department of CIHI has issued
      more than 13,000,000 basic health insurance cards and over 1,500,000 additional
      health insurance cards. Data storage and reporting system as part of the CIHI
      informatics system is essential for analyzing and planning health insurance
      business. CIHI IT has created a modern reporting system with: (a) superior
      performance and power of analytical and reporting possibilities; (b) scalable and
      flexible platform; (c) proactive reporting (Web, SMS, WAP, e-mail, fax, voice);
      (d) web interface for users. The presentation is concluded with basic information
      on the current projects such as introduction of digital signature in CIHI and
      plans for the introduction of smart cards instead of plastic cards with magnetic
      strip. Today, CIHI IT plays the major role in the process of health system
      computerization in Croatia. CIHI is technically and personnel equipped for
      computerization of the entire health system. The informatics system of CIHI can
      serve as a backbone for the informatics health system in the future.

PMID- 16095202
TI  - [ICPC-2--international classification of primary health care and its application
      in Croatian health care].
AB  - A consensus reached by the medical profession, Croatian Institute of Health
      Insurance, Croatian Institute of Public Health, and Ministry of Health
      constitutes a solution to the problem of a data standard required in building an
      information system for primary health care. This consists of accepting ICPC-2 as
      a data standard for our Family Medicine, Pediatrics and Women's Health. The
      classification structure of the International Classification of Primary Care
      allows, recommends and urges that special codes be established by individual
      states or local authorities when registering patients' reasons for seeking
      medical aid or medical procedures. Namely, it urges the authorities to set the
      codes for such reasons about which a state or local agreement or determination
      has been made. This is the first public presentation of the proposal Croatia's
      Additions to the International Classification of Primary Care. They are essential
      to its implementation in our health insurance, health statistics and medical
      informatics.

PMID- 16095203
TI  - [HL7 standard--features, principles, and methodology].
AB  - The mission of HL7 Inc. non-profit organization is to provide standards for the
      exchange, management and integration of data that support clinical patient care,
      and the management, delivery and evaluation of healthcare services. As the
      standards developed by HL7 Inc. represent the world's most influential
      standardization efforts in the field of medical informatics, the HL7 family of
      standards has been recognized by the technical and scientific community as the
      foundation for the next generation healthcare information systems. Versions 1 and
      2 of HL7 standard have solved many issues, but also demonstrated the size and
      complexity of health information sharing problem. As the solution complete new
      methodology has been adopted that is encompassed in the HL7 Version 3
      recommendations. This approach standardizes Reference Information Model (RIM),
      which is the source of all derived domain models and message structures. Message
      design is now defined in detail, enabling interoperability between loosely
      coupled systems that are.designed by different vendors and deployed in various
      environments. At the start of the Primary Healthcare Information System project
      in the Republic of Croatia in 2002, the decision was to go directly to Version 3.
      The target scope of work includes clinical, financial and administrative data
      management in the domain of healthcare processes. By using HL7v3 standardized
      methodology we were able to completely map the Croatian primary healthcare domain
      to HL7v3 artefacts. Further refinement processes that are planned for the future
      will provide semantic interoperability and detailed description of all elements
      in HL7 messages. Our HL7 Business Component is in constant process of studying
      different legacy applications, making solid foundation for their integration to
      HL7-enabled communication environment.

PMID- 16095204
TI  - [Data sources on drug utilization in Croatia and Europe].
AB  - The costs for drugs account for a significant proportion of total health care
      cost in every country. This is especially pronounced in welfare states and less
      developed countries. Therefore, each government has to take protective measures
      against uncontrolled rise in drug expenses and tend to the ideal, rational drug
      utilization. One of these measures is systematic monitoring of drug utilization.
      The data on drug utilization thus obtained provide a basis for appropriate
      interventional measures and their evaluation. In Croatia, no systematic measures
      in the field of drug utilization have yet been employed. In this brief survey,
      the methodology of drug utilization monitoring is critically reviewed,
      emphasizing the need of implementing the World Health Organization (WHO)
      Anatomical-Therapeutic-Chemical (ATC) system of drug classification and drug
      utilization monitoring by use of WHO Defined Daily Doses (DDD). The use of
      ATC/DDD system and other methods of drug utilization monitoring in Scandinavian
      countries is then presented. The third section deals with the current situation
      concerning data sources on drug utilization in Croatia. In Croatia, the ATC/DDD
      system has to date been only used by researchers and Zagreb Institute of Public
      Health in the work on the project entitled Drug Utilization in the City of
      Zagreb, launched in 2002.

PMID- 16095205
TI  - [Normal pressure hydrocephalus after subarachnoid hemorrhage and TGF-beta1
      induced mouse hydrocephalus].

PMID- 16095206
TI  - [Carotid endarterectomy with patch angioplasty].

PMID- 16095207
TI  - [The usefulness of adjuvant therapy using gamma knife radiosurgery for the
      recurrent or residual nonfunctioning pituitary adenomas].
AB  - We evaluated the treatment results of nonfunctioning pituitary adenomas in the
      era of radiosurgery. Between January 1994 and December 2003, we operated on 44
      patients with nonfunctioning pituitary adenomas. 43 patients were operated on by
      transsphenoidal surgery and one patient was operated on by the transcranial
      approach. Total removal was able to be achieved in 13 patients (30%). Gamma knife
      radiosurgery was performed for residual tumor in 26 patients and for recurrence
      in 2 patients. The mean tumor diameter at the gamma knife radiosurgery was 18.2
      mm (7.9 to 26.3 mm). The treatment dose was a mean of 12.3 Gy (8 to 16 Gy) to the
      tumor margin. The mean follow-up period after radiosurgery was 36.4 months. Tumor
      growth control was able to be achieved in 26 patients (93%). Two patients (7%)
      required adrenal and thyroid hormonal replacement during the follow-up period
      after radiosurgery due to radiation-induced endocrinopathy. None of the patients
      suffered from new cranial nerve deficits. This included optic neuropathy.
      Surgical resection using transsphenoidal surgery and subsequent gamma knife
      radiosurgery for residual and recurrent tumor proved to have a highly effective
      tumor growth control rate, and maintained the quality of life in patients with
      nonfunctioning pituitary adenomas.

PMID- 16095208
TI  - [The use of endoscopic surgery for chronic subdural hematoma].
AB  - The surgical procedures for treating chronic subdural hematoma (CSH) are carried
      out with a variety of different methods. The generally used operative method is a
      less invasive burr hole irrigation under local anesthesia. Recently, we have
      devised a new simple method using an endoscope to treat CSH. We have been using
      an endoscopically guided method in which a drainage tube is inserted in the
      hematoma cavity. We also analyzed the endoscopic findings in the hematoma
      cavities and reported a high recurrence rate in patients with clots in the
      hematoma cavity, which suggest the importance of clot removal to reduce
      recurrence. In this study, the advantage of endoscopic surgery for chronic
      subdural hematoma is demonstrated.

PMID- 16095209
TI  - [Subarachnoid hemorrhage caused by a dissecting aneurysm of the internal carotid
      artery: case report and review of the literature].
AB  - A case of subarachnoid hemorrhage (SAH) resulting from a ruptured intracranial
      dissecting aneurysm of the internal carotid artery (ICA) is reported. A 58-year
      old woman presented with headache and vomiting. A CT showed diffuse SAH. A
      cerebral angiography demonstrated a dissecting aneurysm at the C2 segment of the
      right ICA. In the present case, trapping with STA-MCA anastomosis was performed
      and the postoperative course was uneventful. Postoperative follow-up cerebral
      angiogram detected no aneurysm. SAH caused by the rupture of a dissecting
      aneurysm of the ICA has been considered rare. To our knowledge, there have been
      only 29 cases. We discuss the clinical characteristics with a review of the
      literature.

PMID- 16095210
TI  - [A case of non-functional pituitary adenoma associated with Rathke's cleft cyst].
AB  - A very rare case of non-functional pituitary adenoma associated with Rathke's
      cleft cyst is reported. A 42-year-old male suffering from visual disturbance and
      headache was admitted. Visual acuity was 1.2 on the right and 0.5 on the left,
      and visual field examination showed bitemporal hemianopsia. Endocrinological
      study disclosed that the basal serum level of prolactin was elevated slightly to
      52.6 ng/ml, whereas those of other hormones were within normal limits. MRI showed
      a dumbbell-shaped cystic sellar mass extending to the suprasellar region beyond
      the diaphragm sellae, which consisted of two isolated components around the
      sellar turcica. At the middle of May, the tumor was partially removed by
      bifrontal craniotomy. The suprasellar tumor tightly adhered to the frontal lobe
      and the optic nerve, the tumor was grayish cyst and cyst fluid from the
      suprasellar mass had the appearance of motor oil and the intrasellar tumor
      contained old hematoma. Histological findings revealed that the suprasellar mass
      was Rathke's cleft cyst and the intrasellar mass was diagnosed as pituitary
      adenoma (non-functional). Visual acuity was improved following surgical
      operation. So far twenty-three cases of pituitary adenoma associated with
      Rathke's cleft cysts have been reported in the literature, but there was only one
      case reported of a non-functional pituitary adenoma associated with a Rathke's
      cleft cyst. Etiology and pathogenesis of the coexistence of non-functional
      pituitary adenoma and Rathke's cleft cyst in the present case were not
      elucidated.

PMID- 16095211
TI  - [Infected and calcified chronic subdural hematoma presenting an attitude of acute
      hematoma on MRI: case report].
AB  - We report a case of calcified chronic subdural hematoma with unusual magnetic
      resonance imaging (MRI) findings. A 50-year-old male with no marked medical
      history presented with fever for two weeks. Computed tomography (CT) revealed a
      thick, calcified subdural hematoma of low-iso mixed density. MRI showed
      characteristic signals of hematoma in the acute stage. Total removal of the
      hematoma by craniotomy was performed after rapid deterioration of consciousness.
      At surgery, a muddy hematoma and a small amount of pus were seen within the
      calcified capsule. Diagnosis of infected and calcified chronic subdural hematoma
      was established. His symptoms were resolved completely within the following few
      months. As the mechanisms of delayed signal sequence of hematoma on MRI, we
      speculate existence of tissue hypoxia associated with infection and paramagnetic
      effects of free radicals and ions associated with inflammation, necrosis and
      calcification.

PMID- 16095212
TI  - [Percutaneous vertebroplasty combined with radiofrequency ablation for a patient
      with a spinal metastatic tumor: case report].
AB  - Recent technological development has allowed expanding applications of
      radiofrequency ablation (RFA) for malignant tumor therapy. We report a case with
      a spinal metastatic tumor treated with combination of percutaneous vertebroplasty
      (PVP) that provides pain relief and spinal stabilization and RFA. A 68-year-old
      male who had undergone resection of left ureteric carcinoma was referred to our
      hospital with lower back pain due to the fifth lumbar (L5) vertebral metastatic
      tumor. Conventional radiation therapy was discontinued because of pneumonia. One
      year later, the patient was admitted again with weakness of the right knee and
      foot and severe pain of the back and the right lower extremity. Radiographs
      demonstrated a compressive fracture of the L5 vertebra predominantly on the right
      side. CT and MRI showed a tumor of the L5 body invading the right pedicle, the
      intervertebral foramen, and the retroperitoneal space. RFA was performed in the
      ventral part of the L5 body, and then around the right L5/the first sacral
      intervertebral foramen. Temperature and time for ablation ranged from 74 degrees
      C to 95 degrees C and from 11 min. to 30 min., respectively. Next, PVP was
      performed by the right transpedicular approach. Bone cement was injected into the
      L5 body and the pedicle by an amount of 3.0 ml in total without technical
      complications. Postoperatively, visual analogue scale demonstrated decreased pain
      degree from 10 cm to 5.4 cm. Combined treatment with RFA and PVP is a feasible
      and promising procedure for spinal metastatic tumors. Further evaluation is
      necessary to confirm its long-term efficacy.

PMID- 16095213
TI  - [A case of giant cell tumor in atlas].
AB  - We report a rare case of giant cell tumor in the atlas. A 50-year-old female
      presented with severe pain in her right neck and shoulder. The preoperative
      magnetic resonance images showed a tumor mixed with solid and cystic components
      in the right side of the atlas. CT scan showed that the anterior and posterior
      arches of the atlas were destroyed. Preoperative biopsy led to the pathological
      diagnosis of giant cell tumor with multinuclear giant cells and mononuclear
      stromal cells. A preoperative vertebral angiogram demonstrated tumor stain
      supplied from the muscular branches. To reduce intraoperative bleeding, the
      embolization of the right vertebral artery by GDC was performed before surgical
      removal. The tumor was subtotally removed following ligation of the right
      external carotid artery to reduce bleeding of tumor. We used the Olerud cervical
      system to prevent cervical instability after resection of the tumor. Although the
      symptoms disappeared completely after surgery, regrowth of tumor was observed in
      follow-up MRI 4 months after the operation. For this reason, local radiation
      therapy was performed (50 Gy). Then, the size of the tumor has not changed in the
      1.5 years since the operation.

PMID- 16095214
TI  - [Adult choroid plexus papilloma of the posterior fossa: extraventricular
      location].
AB  - Choroid plexus papillomas (CPPs) are rare neuroectodermal neoplasms accounting
      for 0.4% of all intracranial neoplasms in adults. Most of them are located in the
      posterior fossa in adults. Although CPPs commonly arise from the 4th ventricle,
      they occasionally extend to extraventricular space. Furthermore some occur
      primarily in the extraventricular region. It is difficult to diagnose CPP
      preoperatively when the main portion of the tumor is not located in the 4th
      ventricle. We present a case of a 54-year-old male manifesting slurred speech,
      nystagmus and cerebellar ataxia. Magnetic resonance imaging demonstrated an
      intracerebellar solid tumor with multilocular cysts, extending towards both the
      right lateral medullary region and the foramen of Luschka. Computed tomography
      scans showed patchy calcification at the periphery of the solid component.
      Angiographically, via the right posterior inferior cerebellar artery revealed the
      tumor was faintly opacified. Preoperative diagnosis included meningiomas, low
      grade astrocytomas, ependymomas or CPPs, but none of them had neuroradiologically
      decisive findings. Tumor was subtotally resected through a right suboccipital
      craniectomy. A calcified solid portion adhering to the lower cranial nerves was
      left unresected. The pathological finding was CPP. CPP should be considered among
      calcified and enhanced masses in the lateral medullary to cerebellopontine angle
      space in adults, even if the main portion of the tumor is not located in the 4th
      ventricle.

PMID- 16095215
TI  - [Stroke management system: from acute stage to convalescent stage].

PMID- 16095216
TI  - [Rehabilitation at recovery process for stroke patients].

PMID- 16095217
TI  - [Management of stroke patients at rehabilitation ward].

PMID- 16095218
TI  - [Medical care in home for stroke patients].

PMID- 16095219
TI  - [Treatment of carotid artery stenosis: CEA or stent?].

PMID- 16095220
TI  - [AMPA receptor-mediated neuronal death and amyotrophic lateral sclerosis].

PMID- 16095222
TI  - [Intermediate medullary infarction: a case report].
AB  - A 68-year-old man presented with right eye pain and vertigo. Thereafter, he
      gradually leaned rightward, then laid down. He felt nausea and vomited. His right
      upper eyelid drooped and he felt dysethesia of the right hand. On neurological
      examination, ptosis of his right eye with slightly miotic right pupil, paresis of
      the right soft palate and hoarseness were noted. Arm deviation test demonstrated
      rightward deviation. He presented sensory ataxia of the right upper and lower
      extremities: finger nose test showed mild dysmetria of the right upper extremity,
      heel knee test demonstrated dysmetria of right lower extremity and these findings
      worsened when he closed his eyes. He showed mild bending of his bilateral ring
      and little fingers when he did rapid alternative movement. He leaned rightward
      when he sat and closed his eyes. Position sense of his right upper and lower
      extremities was decreased and sometimes he could not answer correctly when asked
      on which direction his finger pointed. Pinprick sensation was mildly decreased on
      the left side not including the face. Touch and vibration sense were normal. SEP
      findings on upper and lower extremity stimulation were normal. MRI of the brain
      showed T2 high intensity and partially T1 low intensity lesion at the right
      medulla (Figure). MR angiography showed no apparent lesion of major arteries such
      as dissection of the vertebral arteries. He complained and presented with hiccup
      initially. On MRI, the lesion was thought to involve the spinothalamic tract,
      medial lemniscus and inferior olivary nucleus. Ambiguus nucleus was in the lesion
      and solitary nucleus near the lesion. There is no report that seems to describe
      clinical features of a lesion like that in this case. Intermediate medullary
      infarction may present dissociated sensory disturbance like Brown-Sequard
      syndrome and position sensory disturbance without disturbance of vibration sense.

PMID- 16095221
TI  - [Acute non-herpetic viral encephalitis of juvenile onset: analysis of 11 cases
      based on initial clinical symptoms].
AB  - We investigated clinical features of juvenile patients presenting non-herpetic
      viral acute encephalitis (4 men and 7 women, aged of onset; 23.7 +/- 3.3 years)
      without malignancy and immunodeficiency. We divided the patients into two groups
      according to initial neurological symptoms: psychiatric symptoms mimicking
      schizophrenia (group P, n=5), seizure (group S, n=6), and compared clinical
      manifestations among the two groups. Symptoms frequently seen in initial phase of
      the illness were neck stiffness (4 cases, 36%), involuntary movement (7 cases,
      64%) and convulsion (8 cases, 73%). There were no significant difference among
      the groups except seizure. Patients in group P had more CSF cells and CSF
      lymphocytes compared with other groups (p < 0.05 and p < 0.01, respectively).
      Abnormal intensities in T2-weighted magnetic resonance images were found in 4
      cases (36%). The term from the onset to leaving hospital of group P (213 +/- 227
      days) was longer than that of group S (98 +/- 85 days), although it did not reach
      a significant difference. These findings indicate that juvenile acute non
      herpetic encephalitis initially presenting psychiatric symptoms was serious and
      had relatively poor prognosis.

PMID- 16095224
TI  - [A case of spinal dural arteriovenous fistula draining to the ventral coronal
      venous plexus].
AB  - Here we report a case of spinal dural areteriovenous fistula (AVF) draining to
      the anterior spinal vein. An 80-year-old female presented with progressive
      weakness of lower extremities. MRI showed spinal enlargement at the Th10 to L1
      with high intensity signals on T2-weighted image and multiple flow voids on the
      dorsal and ventral surface of the spinal cord. Angiogram of the left L2 lumbar
      artery demonstrated a hairpin-shaped vessel with ascending and descending limbs,
      mimicking radiculomedullary artery. Oblique view angiogram of the left L2 lumbar
      artery showed that radiculomedullary vein drained to the dilated anterior spinal
      vein, which then drained cranially and caudally on the anterior and posterior
      surface of the spinal cord. The patient underwent T9-L2 laminectomy. Several
      large tortuous dilated veins in the subarachnoid space were found. Examination of
      the inner surface of the dura revealed an arterialized vein that began at the
      level of L2 and coursed superiorly. The arterialized vein was coagulated and
      interrupted. The postoperative angiogram demonstrated the obliteration of the
      fistula. Postoperative MRI returned to normal with complete disappearance of T2
      high signal, cord enlargement. In most spinal dural AVF, the venous drainage is
      predominantly upward on the posterior surface of the spinal cord. The spinal
      dural AVF draining to the anterior spinal vein is atypical, and cause difficulty
      in differentiating the anterior spinal artery from the anterior spinal vein.
      Oblique view angiogram may be helpful to differentiate the anterior spinal vein
      from anterior spinal artery.

PMID- 16095223
TI  - [A 26-year-old woman of interval form of acute carbon monoxide intoxication with
      cerebrospinal fluid abnormalities].
AB  - A 26-year-old woman was admitted to our hospital for the treatment of hyperbaric
      oxygen therapy to acute carbon monoxide intoxication. The consciousness
      disturbance improved and she was discharged after 23 times of the hyperbaric
      oxygen therapy. However, she was readmitted because of dementia and urinary
      incontinence after 22 days. Diffusion-weighted images showed bright high signal
      intensities in the periventicular white matter and corpus callosum. The condition
      was considered to be an interval form of carbon monoxide intoxication. She was
      treated by 38 times of the hyperbaric oxygen therapy with cytochrome C and fully
      recovered. MRI images and cerebrospinal fluid abnormality (high protein content
      and IgG index) became normalized somewhat later than the improvement of the
      symptoms. By an investigation utilizing diffusion-weighted images, we thought
      that not only the demyelination which mentioned formerly, but the vasogenic edema
      was involving in the mechanism of these high signal intensities in the
      periventicular white matter of the interval form. And in the range which we
      searched, this is the first report which mentioned the abnormal findings of
      cerebrospinal fluid in an interval form of carbon monoxide intoxication. So we
      believe this case is very important for telling us suspected the mechanism and
      some indications about the treatment of an interval form.

PMID- 16095225
TI  - [Does percutaneous coronary intervention in non-culprit vessels improve the
      prognosis of acute myocardial infarction complicated by pump failure?].
AB  - OBJECTIVES: To evaluate whether percutaneous coronary intervention (PCI)in non
      culprit vessel lesions improves the short-term prognosis of acute myocardial
      infarction complicated by pump failure. METHODS: Fifty-six patients with acute
      myocardial infarction in hemodynamic subset 4 of Forrester's classification at
      hospitalization underwent PCI for multiple vessel lesions within 12 hr (6.1 +/-
      3.4 hr) of the onset of acute myocardial infarction. No patients had left main
      trunk lesion. Twenty patients also underwent PCI for non-culprit vessel lesions
      (multivessel PCI group: M-PCI), but the remaining 36 did not (culprit vessel PCI
      group: C-PCI). The in-hospital prognosis was investigated from the hospital
      records. RESULTS: Complete revascularization was accomplished in 18
      patients(90%)in the M-PCI. The rates of all in-hospital death were almost
      equivalent in both groups (M-PCI 30% vs C-PCI 42%, p = 0.21), but the rate of
      cardiac deaths was higher in the C-PCI than in the M-PCI (42% vs 15%, p < 0.05).
      Overall major adverse cardiac events occurred more often in the C-PCI than in the
      M-PCI(58% vs 25%, p < 0.05). Multivariate logistic regression analysis showed
      complete revascularization(odds ratio 0.11, 95% confidence interval 0.02-0.95, p
      < 0.05)and duration from onset of acute myocardial infarction to PCI < 6 hr (odds
      ratio 0.25, 95% confidence interval 0.06-0.98, p < 0.05) were negative predictors
      of in-hospital cardiac death, and prior myocardial infarction (odds ratio 4.97,
      95% confidence interval 1.09-22.67, p < 0.05) was a positive predictor.
      CONCLUSIONS: PCI of non-culprit vessel lesions might improve the short-term
      prognosis of patients with acute myocardial infarction and pump failure.

PMID- 16095226
TI  - Serum heart-type fatty acid binding protein predicts cardiac events in elderly
      patients with chronic heart failure.
AB  - BACKGROUND AND OBJECTIVES: Heart-type fatty acid binding protein (H-FABP) is
      released into the circulation from the damaged myocardium of patients with severe
      chronic heart failure. Chronic heart failure is the most frequent cause of death
      and disability in the elderly. However, there are no data for the prognostic
      value of H-FABP in the elderly population. This study investigated whether H-FABP
      can effectively predict the prognosis in elderly patients (> or = 70 years) with
      chronic heart failure. METHODS: Serum H-FABP levels were measured in 90 chronic
      heart failure patients > or =70 years old (mean age 77 +/- 4 years, range 70-92
      years), and patients were followed-up for 421 +/- 326 days. RESULTS: There were
      35 cardiac events (38.9%) including cardiac deaths and readmissions for worsening
      chronic heart failure. Multivariate analysis with the Cox proportional hazard
      model showed that H-FABP was the only independent predictor of cardiac events
      (chi2 = 6.640, p = 0.0100). Kaplan-Meier analysis revealed that H-FABP
      effectively risk stratified elderly patients with chronic heart failure for
      cardiac events. CONCLUSIONS: These findings suggest that H-FABP is a reliable
      marker for prognosis in elderly patients with chronic heart failure.

PMID- 16095227
TI  - Relationship between mitral annular calcification and severity of carotid
      atherosclerosis in patients with symptomatic ischemic cerebrovascular disease.
AB  - OBJECTIVES: Many studies have reported the association between mitral annular
      calcification (MAC) and stroke. MAC has been speculated to be a direct embolic
      source of stroke. Recently, the association between MAC and atherosclerosis in
      the coronary artery, aorta, and carotid artery has been reported. This
      prospective study investigated the association between MAC and severity of
      carotid atherosclerosis in patients with symptomatic ischemic cerebral disease to
      evaluate the association between MAC and atherosclerosis as a cause of stroke.
      METHODS: We studied 377 patients with ischemic cerebral disease (253 men, 124
      women, mean age 68 +/- 11 years) who underwent echocardiography to determine the
      presence of MAC and carotid ultrasonography to determine the severity of carotid
      atherosclerosis. Plaque score was the sum of the maximum intimamedia thickness in
      the common carotid region, the bifurcation bulb region, and the internal carotid
      artery region, including both right and left arteries. RESULTS: MAC was found in
      86 patients, and was more frequent in women, the elderly, and patients with
      diabetes or hyperlipidemia (p < 0.05). Plaque score was higher in patients with
      than without MAC (8.3 +/- 5.8 vs 5.2 +/- 5.2 mm, p < 0.001). Multivariate
      regression analysis identified MAC (r = 0.26, p < 0.0001), female sex (r = -0.12,
      p = 0.03), and age (r = 0.23, p < 0.0001) as independently associated with plaque
      score. CONCLUSIONS: MAC is independently associated with severity of carotid
      atherosclerosis in patients with symptomatic ischemic cerebral disease. This
      association suggests MAC may be indirectly related to cerebrovascular disease as
      a marker of the presence of progressive arteriosclerosis for thromboemboli
      causing stroke.

PMID- 16095228
TI  - [Fulminant myocarditis causing severe left heart failure and massive thrombus
      formation following cardiac tamponade: a case report].
AB  - A woman aged middle thirties presented with common cold-like symptoms, and was
      hospitalized due to hypotension and tachycardia. Echocardiography revealed
      pericardial effusion and preserved left ventricular fractional shortening (28%).
      Cardiac index, pulmonary capillary wedge and right atrial pressure were 1.8
      l/min/m2, 15 and 13 mmHg, respectively. After drainage of pericardial effusion,
      cardiac index increased to 3.4 l/min/m2. On the fifth hospital day, left
      ventricular dysfunction developed (fractional shortening: 16%, cardiac index: 1.5
      l/min/m2, pulmonary capillary wedge pressure: 18 mmHg, right atrial pressure: 12
      mmHg), so percutaneous cardiopulmonary support was introduced. However, the heart
      failed in asystole and the cavity was occupied by massive thrombus, probably
      related to heparin-induced thrombocytopenia. This case of fulminant myocarditis
      passed through various clinical features of heart failure. She died on the 12th
      hospital day.

PMID- 16095229
TI  - Silent pulmonary artery dissection in a patient with Eisenmenger syndrome due to
      ventricular septal defect: a case report.
AB  - A 62-year-old woman was admitted to our hospital because of fever in August 2002.
      She had been treated under a diagnosis of Eisenmenger syndrome with ventricular
      septal defect since 1988. On admission, echocardiography and color Doppler
      echocardiography revealed a markedly enlarged pulmonary artery with a mobile
      flap, and dissection of the pulmonary artery. The origin of the fever could not
      be identified, and the fever subsided spontaneously without specific treatment.
      She had no chest pain, but fever might have been a sign of dissection in this
      patient. Longstanding pulmonary hypertension may cause dissection, which may lead
      to sudden death or pulmonary hemorrhage often seen in patients with Eisenmenger
      syndrome. Our patient was a rare survivor without serious bleeding complication.

PMID- 16095230
TI  - Low washout rate during stress thallium-201 myocardial scintigraphy. Transient
      left ventricular dysfunction in a patient with grant splenomegaly due to
      polycytemia vera.

PMID- 16095231
TI  - Managing surgical quality based on database.

PMID- 16095232
TI  - Recent experiences with minimally invasive pectus excavatum repair "Nuss
      procedure".
AB  - OBJECTIVE: To review the new technical modifications and results of 668 patients
      who have had pectus excavatum repair utilizing the minimally invasive technique.
      METHODS: A retrospective chart review was conducted of 668 patients undergoing
      minimally invasive pectus repair from 1987 through July 2004. Since 1997, a
      standardized treatment pathway was implemented. Preoperative evaluation included
      computed tomography (CT) scan, pulmonary function tests, and cardiac evaluations
      with electrocardiogram and echocardiogram. Indications for operation included at
      least 2 of the following: progression of the deformity, Haller CT index greater
      than 3.25, mitral valve prolapse, cardiac compression or displacement, pulmonary
      function studies that indicate restrictive or obstructive airway disease,
      previous failed open or minimally invasive pectus repair. Technical and design
      modifications since 1998 have included routine thoracoscopy, the use of an
      introducer/dissector for creating the substernal tunnel, elevating the sternum,
      and routine use of a wired lateral stabilizer and polydioxanone suture (PDS)
      sutures around the bar and underlying rib to prevent bar displacement. The bar is
      removed as an outpatient procedure in 2 to 4 years. RESULTS: In 668 patients
      undergoing minimally invasive pectus repairs, single bars were used in 78.1% and
      double in 21.7%. Lateral stabilizers were applied in 99.8% and were wired for
      further stability in 71%. Bar shifts before the use of stabilizers were 14.3%,
      which decreased to 4.6% after stabilizers were placed and 0.8% with a wired
      stabilizer and PDS sutures. Results were excellent in 78.5%, good in 13.1%, fair
      in 4.7% and failed in 3.7% after more than 1 year post bar removal. CONCLUSION:
      The minimally invasive technique has evolved into an effective method of pectus
      excavatum repair. Modifications of the technique have reduced complications. Long
      term results continue to be excellent.

PMID- 16095233
TI  - Risk of recurrence after surgical resection of small-sized invasive lung
      adenocarcinoma: analysis based on apoptotic index.
AB  - OBJECTIVE: It has been reported that small-sized invasive lung adenocarcinomas,
      i.e., those classified as type C through type F according to Noguchi's
      classification, may also recur even after complete resection. We evaluated the
      prognostic value of molecular biologic markers (apoptosis, Ki-67, p53, epidermal
      growth factor) and clinicopathological factors in patients with small-sized
      invasive lung adenocarcinomas. METHODS: The clinical records of all patients who
      had had a peripheral adenocarcinoma surgically resected between 1996 and 2002,
      and histologically diagnosed as type C through type F according to Noguchi's
      classification were retrospectively reviewed. The apoptotic index (AI) was
      determined by the triphosphate biotin nick end-labeling method and the expression
      of Ki-67, aberrant p53 protein and epidermal growth factor receptor was
      determined by immunohistochemical staining. RESULTS: Data from 28 patients who
      had been followed up for a mean period of 41.8 months (range: 16 to 89 months)
      were evaluated. During the follow-up period, recurrence was seen in 6 patients.
      The log-rank test showed that AI was a significant predictor of cancer
      recurrence. The 5-year disease-free survival rate of the 10 patients in the high
      AI group (AI > 0.3%) was 100%; while that of the 18 patients in the low AI group
      (AI < or = 0.3%) was 50.5% (p = 0.036). None of the other molecular biologic
      markers or clinicopathological factors were found to be a significant predictor
      of cancer recurrence. CONCLUSION: Peripheral small-sized invasive lung
      adenocarcinomas with a low AI carry an increased risk of distant metastases,
      indicating that adjuvant chemotherapy after complete resection might be needed.

PMID- 16095234
TI  - Late outcomes after isolated coronary artery bypass grafting for ischemic mitral
      regurgitation.
AB  - OBJECTIVES: Although ischemic mitral regurgitation (IMR) is one of the most
      important issues to determine therapeutic strategy for ischemic heart disease,
      long-term outcome after coronary artery bypass grafting (CABG) for IMR is still
      unclear. It is also controversial how patients who would benefit from mitral
      valve (MV) surgery in combination with CABG should be identified. The purpose of
      this study is to elucidate late outcomes after isolated CABG for moderate IMR and
      to assess the indication of combined MV surgery. METHODS: Two hundred and seventy
      nine patients who had grade 2 or 3 IMR preoperatively and underwent isolated CABG
      between 1980 and 2002 in our institute were enrolled. Mitral regurgitation was
      assessed by 2-dimensional Doppler echocardiography and left ventriculography.
      Among them, 84 patients (30.1%) had left ventricular ejection fraction (LVEF)
      less than 30% and 186 patients (66.7%) had prior inferior myocardial infarction
      (MI). RESULTS: One hundred and twenty-nine patients (46.2%) remained grade 2 or
      greater MR early postoperatively. Actuarial survival and freedom from cardiac
      events, analyzed by the Kaplan-Meier method, were 90.9% and 87.7% at 1 year,
      79.2% and 68.8% at 5 years, 54.9% and 49.1% at 10 years and 48.8% and 18.9% at 15
      years. Independent predictive risk factors for cardiac events, analyzed by
      multivariate analysis using the Cox proportional hazard model, were grade 2 or
      greater MR which remained early postoperatively (p = 0.0002), LVEF < 30%
      preoperatively (p = 0.0006), no inferior MI preoperatively (p = 0.007) and no
      internal thoracic artery-left anterior descending artery graft (p = 0.049). More
      than a 15% decrease in LVEF at more than 3 years after the operation was seen
      despite patent bypass grafts in 17.2% of patients who received a late follow-up
      catheterization, although 41.4% of patients showed an increase or less than 5%
      decrease in LVEF during this period. CONCLUSION: Combined MV surgery with CABG
      for IMR should be considered in patients with poor LVEF or without prior inferior
      MI.

PMID- 16095235
TI  - Postoperative mediastinitis following hemiarch replacement: successful treatment
      using omental flap transposition.
AB  - Although various strategies have been advocated for mediastinitis following
      cardiac operations, surgical results for this complication remain a significant
      concern. The condition would be more complicated with replacement of the
      ascending aorta using a prosthetic graft. We present the case of a 50-year-old
      female patient with acute aortic dissection who underwent hemiarch replacement
      using a prosthetic graft and concomitant coronary artery bypass grafting, and
      developed periprosthetic purulent collection 2 months later. Successful treatment
      involved debridement ofinfected tissues and omental flap transposition.
      Postoperative chest computed tomography revealed no sign of perigraft infection.
      Omental flap transposition can be effective for treating mediastinitis following
      prosthetic graft replacement of the ascending aorta. The patient has remained in
      good health for 1 year, with no signs of recurrent graft infection or
      pseudoaneurysm formation.

PMID- 16095236
TI  - Sudden death from metastatic esophageal cancer to the ventricular septum.
AB  - A 67-year-old man was admitted to our hospital due to esophageal cancer. Cancer
      existed at the lower esophagus and subtotal esophagectomy and lymphadenectomy was
      performed. The postoperative course was uneventful. Pathological findings
      revealed moderately differentiated squamous cell carcinoma that metastasized to
      the abdominal lymph nodes which include the paraaortic lymph nodes. He complained
      of anorexia three months after the operation and was found to have multiple liver
      and mediastinal lymph node metastases. He was admitted for chemotherapy. Before
      starting chemotherapy, he suddenly died without any sign of hemorrhage or
      respiratory disorder. Autopsy showed metastatic lesions to the heart and
      mediastinal lymph nodes, liver, thoracic vertebrae, kidney, adrenal gland and
      heart. Metastatic nodules in the heart were on the ventricular septum where the
      conducting system exists. No direct invasion from the pericardium was observed.
      Blockade of the conducting system of the heart was considered to have caused the
      severe arrhythmia and sudden cardiac arrest.

PMID- 16095237
TI  - Pulmonary cryptococcosis mimicking pulmonary metastases in a patient treated with
      Tegafur-uracil after lung cancer surgery.
AB  - A 71-year-old man who had undergone surgery for stage II adenocarcinoma of the
      lung followed by adjuvant tegafur-uracil (UFT; 300 mg/day) therapy was admitted.
      Multiple nodules were found in both lungs on chest radiographs obtained 1.5 years
      after the surgery. Imaging characteristics of the nodules resembled those of
      pulmonary metastases. Histologic assessment of a biopsy specimen obtained during
      thoracoscopic resection revealed pulmonary cryptococcosis. The patient was
      administered 200 mg/day fluconazole for 6 months. Physicians need to be aware of
      the possibility of pulmonary cryptococcosis mimicking pulmonary metastases in
      patients treated with UFT after surgery for lung cancer.

PMID- 16095239
TI  - Primary mediastinal lymph node malignancy with features suggestive of dendritic
      cell sarcoma.
AB  - A 56-year-old man underwent preoperative chest computed tomography to further
      evaluate a well defined mass in the middle lobe with subcarinal lymph node
      swelling. There was no pathological diagnosis established by either bronchoscopic
      biopsy specimens or computed tomography-guided percutaneous needle biopsy. The
      middle lobe and mediastinal lymph nodes were excised, then postoperative
      radiotherapy (60 Gy) was administered to the mediastinum. Results of histological
      and immunohistochemical study showed that the lung mass consisted of completely
      necrotic tissue and that the subcarinal lymph node was involved by malignant
      cells suggestive of dendritic cell sarcoma. Primary dendritic cell sarcoma of the
      mediastinal lymph node is extremely rare. Dendritic cell sarcoma is a neoplasm of
      reticular dendritic origin and includes both follicular dendritic cell sarcoma
      and interdigitating reticulum (or dendritic) cell sarcoma. These rare neoplasms
      may pose difficulty in pathologic diagnosis and treatment. Although our patient
      died of hepatic rupture due to dendritic cell sarcoma or gastric cancer
      metastases one year after surgery, complete surgical resection with or without
      postoperative radiotherapy may be an acceptable therapeutic option for localized
      dendritic cell sarcoma.

PMID- 16095238
TI  - Combined aortic and mitral valve repair in active infective endocarditis.
AB  - We describe a case of successful combined repair of the aortic and mitral valves
      for an indication of active infective endocarditis involving both valves. Mitral
      valve repair was achieved by vegetation debridement, fixation of the anterior
      mitral commissure, resection and suturing of the posterior mitral leaflet, and
      posterior annuloplasty with autologous pericardium. Aortic valve repair was
      achieved by vegetectomy and commissural plication. Postoperative clinical course
      was without signs of recurrent infection, and echocardiogram demonstrated mitral
      valve competence with trivial aortic regurgitation. We concluded that
      simultaneous valve repair is a viable option in the context of active
      endocarditis.

PMID- 16095240
TI  - Pitfalls of sutureless repair of a blow-out type left ventricular free wall
      rupture.
AB  - A 55-year-old man was admitted for acute myocardial infarction. Cardiac
      catheterization revealed total occlusion of the left circumflex artery. During
      catheterization, he suffered cardiogenic shock. Percutaneous cardiopulmonary
      support was established, and the patient was transferred to the operating room. A
      blow-out left ventricular free wall rupture (LVFWR) with an epicardial tear, 1 mm
      in diameter, was found, and sutureless repair with a collagen hemostat
      (TachoComb) was performed. However, on postoperative day 7, echocardiography
      revealed an echo-free space resembling a pseudoaneurysm. A second operation was
      performed immediately for impending re-rupture. An epicardial tear, 2 x 10 mm in
      diameter, was found at the previous bleeding point where hemostasis had been
      achieved with only one sheet of TachoComb. The defect was closed with mattress
      sutures buttressed with Teflon felt. We conclude that even if the risk of re
      rupture is low, sutureless repair with a collagen hemostat alone should be
      avoided in treating blow-out LVFWR.

PMID- 16095241
TI  - Huge thrombus growing on an aortic prosthetic valve detected in acute coronary
      syndrome.
AB  - A 74-year-old woman with a history of aortic valve replacement (AVR) with a
      tilting prosthesis at the age of 59 was referred to our hospital with chest pain
      at rest. Following conservative treatment after admission, the laboratory
      findings demonstrated acute myocardial infarction. Although bilateral coronary
      arteries exhibited no significant stenosis and embolism on the emergency coronary
      angiogram, a huge mobile mass above the prosthetic valve was recognized on the
      aortography, computed tomography, and trans-esophageal echocardiography.
      Operative findings demonstrated that the huge mobile thrombus was growing from
      the sawing ring on the side of minor orifice and almost covered the ostium of the
      left coronary artery. Emergency re-AVR with 21 mm SJM HP valve was performed.
      This clinical course suggested that the acute coronary syndrome might be caused
      by the isolated thrombus on the aortic prosthetic valve without any insufficiency
      of prosthesis and embolic findings due to the thrombosed valve.

PMID- 16095242
TI  - Emergency operation for distal aortic arch aneurysm in Behcet's disease.
AB  - Arterial complications of Behcet's disease rarely affect the thoracic aorta, and
      the incidence of aortic arch aneurysm is especially low. We present a patient who
      developed a rapidly expanding aneurysm of the distal aortic arch after 20 years
      of treatment of Behcet's disease. Emergency total arch replacement was performed
      with a favorable outcome. Graft anastomosis to the normal aorta involving all
      three layers, wrapping of the anastomotic sites with wide felt strips, as well as
      strict management of systemic inflammation are essential for prevention of late
      complications associated with graft anastomosis sites.

PMID- 16095243
TI  - Oncocytic carcinoid of the lung.
AB  - A 49-year-old male was hospitalized after chest roentgenogram revealed a coin
      lesion in the right of middle lung field. Right upper lobectomy with
      lymphadenectomy was performed. The diagnosis on pathological examination was of
      carcinoid tumor. However, electron-microscopic examination revealed hyperplasia
      of numerous mitochondria and neurosecretory granules in the cytoplasm of the
      tumor cell, thus the diagnosis of oncocytic carcinoid was made. The patient has
      been well and experienced neither recurrences nor relapse 2 years after the
      surgery.

PMID- 16095244
TI  - Spontaneous disappearance of focal ground-glass opacity in the lung detected on
      the high-resolution computed tomography.
AB  - We report a case of a 52-year-old female with spontaneous disappearance of focal
      ground-glass opacity (GGO) detected on high-resolution computed tomography
      (HRCT). She initially was found to have a focal GGO lesion on follow-up computed
      tomography five years after left lower lobectomy for primary lung adenocarcinoma.
      Two months later, this lesion spontaneously disappeared in spite of the suspicion
      of subsequent lung cancer. A GGO appearance on HRCT can be found in a variety of
      diseases with partial air-space filling or interstitial thickening. Lung cancer,
      especially bronchioloalveolar carcinoma, is also included in the differential
      diagnosis for GGO lesions. However, there is little definite evidence about the
      management of lesions showing a GGO appearance. When we detect a GGO lesion,
      initial monitoring for several months may be useful for excluding the presence of
      lung neoplasms.

PMID- 16095245
TI  - Temporary decompression of the right ventricle to assess the right ventricle
      dependent coronary circulation in pulmonary atresia with intact ventricular
      septum.
AB  - We repaired a case of pulmonary atresia with intact ventricular septum in which
      the blood supply to the left anterior descending coronary artery depended on the
      right ventricle. At the time of a bidirectional Glenn operation, total
      cardiopulmonary bypass with venous drainage from the right atrium was performed
      in order to evaluate the safety of right ventricular decompression required for a
      planned Fontan operation. We confirmed the dependence of the coronary perfusion
      on the right ventricle by demonstrating transient depression of the ST segment in
      the epicardial electrocardiogram during temporary decompression of the right
      ventricle. To prevent ischemic myocardial damage, we then performed an
      extracardiac Fontan operation with a temporary venous shunt and without
      cardiopulmonary bypass.

PMID- 16095246
TI  - Arterial air embolism during percutaneous pulmonary marking under computed
      tomography guidance.
AB  - Percutaneous pulmonary marking under computed tomography (CT) guidance is often
      used to identify the location of small nodules prior to pulmonary wedge resection
      by video assisted thoracoscopic surgery. Although pneumothorax and pulmonary
      hemorrhage are known complications that accompany this method, arterial air
      embolism is an extremely rare and occasionally fatal complication. We report a
      case of arterial air embolism during percutaneous pulmonary marking under CT
      guidance. Percutaneous pulmonary marking was performed in the prone position in a
      59-year-old male with a right lung nodule. The chest CT performed immediately
      after this procedure revealed an air-fluid level in the heart. The skin of the
      patient's back appeared cyanotic and neurological dysfunction was noted in his
      left thigh, although his vital signs were stable. Four hours later, the air in
      the heart and aorta disappeared, as observed by a chest CT. The patient underwent
      pulmonary resection 12 days later.

PMID- 16095247
TI  - Emergent mitral valvuloplasty with an autologous pericardial patch in an
      octogenarian with active infective endocarditis.
AB  - An 83-year-old woman with suppurative spondylitis was referred to our hospital
      due to active infective endocarditis with an expanding mobile vegetation and a
      high echoic mass on the posterior mitral leaflet. During the operation, the high
      echoic mass was found to be a chronically organized abscess, which was located at
      the base of the vegetation on the posterior leaflet and extended toward the
      annulus. The patient underwent a successfully emergent resection of the
      vegetation and mass, and valvuloplasty using an autologous pericardial patch with
      an excellent outcome.

PMID- 16095249
TI  - Allergic reaction.

PMID- 16095250
TI  - Ending child poverty.

PMID- 16095252
TI  - Evaluating family partnership training in health visitor practice.
AB  - The second paper in this series of two on partnership examines the effects of
      family partnership (parent adviser) training which builds on health visitors'
      skills to facilitate partnership working with parents. This study was utilised as
      a pilot to identify a suitable method, to explore the interaction processes of
      health visitors who had undergone the training. The study draws together both
      quantitative and qualitative methods to seek to understand processes in depth.
      Three health visitors, who were part of a training group of 12, took part in the
      qualitative research using stimulated recall methodology. The quantitative data
      was collected from the whole training group using the Constructions of Helping
      questionnaire and the course evaluation form. The findings suggest that the
      family partnership training may be effective in enhancing partnership working in
      health visiting and that the stimulated recall methodology is an effective method
      of identifying the processes of interaction. The triangulation of methods led to
      an understanding that change in practice is dependent on the insight of the
      practitioner and that this may be able to be measured to some extent by the use
      of different methods.

PMID- 16095253
TI  - Home visiting and child health surveillance attendance.
AB  - This project tested the hypothesis that low attendance rates at a Sure Start
      child health surveillance session might increase if appointments were preceded by
      intervention home visits from research assistants drawn from the local community.
      The assistants would explain the purpose of surveillance and discuss problems
      preventing attendance. A randomised control trial showed no increase in
      surveillance attendance after two-thirds of the intervention group were
      successfully visited. This negative finding was despite the partnership with
      local people acting as research assistants working well. Other factors that might
      have influenced attendance were investigated at an evaluation interview
      undertaken by community members in homes after the surveillance date. Only 55 per
      cent of the families could be contacted for evaluation. Six out of 10 of those
      who had no evaluation were the same families who had not attended the
      surveillance session. The reasons why these families missed surveillance sessions
      is yet to be identified. Further research is needed that explores the reason why
      some families do come for surveillance, the nature of the barriers to attendance
      in those who do not attend and to look for opportunities for fresh interventions
      that might give more children access to pre-school facilities.

PMID- 16095254
TI  - Experiencing a dilemma--accounts of working with PND.
AB  - Various ways of thinking about postnatal depression (PND) are evident from the
      literature. From the clinical-medical perspective, it is an illness of the
      individual mother. The social approach locates its cause in the environment
      Feminists/social constructionists have critiqued such models as problematising
      women--they see them as pressured by oppressive forces such as society's
      stereotype of 'the joy of motherhood'. From the psychoanalytic perspective it
      arises from unrecognised conflict and ambivalence, related to the re-emergence of
      conflict between the mother and her own parents. Health visitors working with PND
      -the frontline of health professionals in this aspect of maternal mental health-
      stand between the professional/academic accounts on the one hand, and the lay
      accounts of their clients on the other. The aim of this study was to examine how
      health visitors understand and make sense of PND. We adopted qualitative research
      methodology to analyse transcripts from interviews with eight health visitors
      about their work with PND. The findings demonstrate the diverse roles they have
      to adopt, and the complexity and lack of clarity of the very concept of PND
      itself. There were clearly ambiguities and dilemmas of thinking involved--not
      apparent from the literature, tensions with which the participants struggled. A
      subsequent paper will present training to address these issues.

PMID- 16095255
TI  - Maintaining healthy skin in infancy using prevention of irritant napkin
      dermatitis as a model.
AB  - Irritant napkin dermatitis is a form of contact dermatitis that occurs in the
      nappy area as a consequence of the disruption of skin barrier integrity by
      prolonged contact with faeces and urine. It is a condition that still occurs
      regularly in young children, and is best managed by prevention. In this update,
      we will consider the reasons that irritant napkin dermatitis develops, and the
      simple methods that parents can adopt to avert it. These methods are equally
      appropriate for general skin care in babies, with the aim of preventing atopic
      dermatitis, another exceedingly common skin problem in this age group.

PMID- 16095259
TI  - The doctor and the doctor.

PMID- 16095260
TI  - Case report on motor neuropathy associated with herpes zoster.
AB  - BACKGROUND: Complications associated with herpes zoster are primarily sensory,
      but motor involvement, especially in late life, can be part of the symptom
      complex. CASE REPORT: We report a case of herpes zoster with motor neuropathy in
      a 66-year-old female. Eighteen months after diagnosis and treatment, the patient
      is regaining muscular strength in the affected limb. DISCUSSION: Treatment of
      motor neuropathy mainly consists of physical and occupational therapy. Most
      patients achieve functional recovery.

PMID- 16095261
TI  - Kentucky Homeplace Defeat Diabetes Screening Test: an analysis of rural
      Kentucky's challenge to overcome the growing diabetes epidemic.
AB  - The University of Kentucky Center for Rural Health original research note,
      "Kentucky Homeplace Defeat Diabetes Screening Test: An Analysis of Rural
      Kentucky's Challenge to Overcome the Growing Diabetes Epidemic," provides the
      results of a yearlong diabetes risk survey that included more than 3,000
      participants in rural Kentucky. It is well known that diabetes poses serious
      health threats across our country. For various reasons, that is especially true
      in Kentucky, with rural Kentucky having the highest prevalence for the disease.
      From September 2002 through August 2003, lay health workers with the nationally
      recognized Kentucky Homeplace program distributed and processed 3,092 diabetes
      self-test surveys to their clients across five regions of the state to get a
      better picture of the diabetes epidemic. The screening test was developed as an
      educational and public awareness tool by the Defeat Diabetes Foundation Inc, a
      nonprofit organization based in Madeira Beach, FL. It was distributed to various
      health agencies across the country. Each survey contained 16 questions, ranging
      from determining participants' urinary frequency and family medical history to
      their age and weight. Zero, five, or 10 points were allotted depending on
      respondents' degree of incidence for each question. A score of 0-15 points
      suggested a low risk for having diabetes, 20-25 points suggested that a
      respondent was at medium risk and should be tested for the disease, and a score
      of 30 points or higher suggested that he/she was at very high risk and "should
      seek (a) medical evaluation right away." Several months of analysis of the data
      collected indicated that 74.6% of the Kentucky Homeplace clients who participated
      in the survey were at moderate to significant risk of having or developing
      diabetes, a much higher rate than the approximately 50% of Kentucky adults in the
      general population that previous studies indicated were at risk. While findings
      from the survey of more than 3,000 Kentucky Homeplace clients cannot be
      generalized to Kentucky's population as a whole, they further confirm other
      evidence indicating that diabetes will continue to be one of the most serious
      health threats facing the state's rural populations. The research note further
      offered some recommendations for curbing rural Kentucky's diabetes epidemic,
      including increasing the number of certified diabetes educators serving rural
      Kentucky, expanding lay health worker programs within the rural portions of the
      Commonwealth, and studying the method and effectiveness of diabetes education
      between physicians and patients.

PMID- 16095262
TI  - Termination of employment.

PMID- 16095263
TI  - A contrarian's views on residency work-hour reforms.

PMID- 16095265
TI  - [Public sector, private sector, the missions and challenges].

PMID- 16095266
TI  - [Making a career in the public sector].

PMID- 16095267
TI  - [Succeeding at each step in searching for employment].

PMID- 16095268
TI  - Clinical approaches to migraine prophylaxis.
AB  - Chronic migraine is a recognized complication of episodic migraine. A high
      frequency of attacks and frequent use of abortive medications are important risk
      factors associated with conversion to a chronic condition. Prophylaxis is
      therefore recommended for patients with frequent episodic migraine. The agents
      approved for migraine prophylaxis are the anti-epileptic agents divalproex and
      topiramate, and the beta-adrenergic antagonists propranolol and timolol. However,
      a wide range of other systemic agents and local injections of botulinum toxin
      have also been used in migraine prophylaxis. The anticipated benefits must be
      weighed against the adverse effects associated with each agent in determining the
      optimal preventive regimen for individual patients.

PMID- 16095269
TI  - The cost of migraine and its treatment.
AB  - Migraine headache incurs estimated annual costs totaling as much as 17 billion
      dollars in the United States. Most of the direct costs are for outpatient
      services: medications, office or clinic visits, emergency department visits,
      laboratory and diagnostic services, and management of treatment side effects.
      Indirect costs from lost productivity in the workplace add substantially to the
      total. The triptan class of drugs, used for abortive treatment, account for the
      greatest portion of medication costs. Because these agents are expensive, optimal
      use is critical. Research suggests that a stratified care strategy, with initial
      therapy based on the patient's score on the Migraine Disability Assessment Scale,
      is both clinically advantageous and more cost-effective than stepped-care
      strategies. Also, the triptans are not interchangeable, and costs as well as
      clinical outcomes may vary with different agents in this class. Migraine
      prophylaxis is aimed at preventing frequent attacks and the development of a long
      term condition that often incurs heavy costs for abortive treatment, diagnostic
      services, and medical care. Agents approved for migraine prophylaxis include the
      antiepileptics divalproex and topiramate and the beta blockers propranolol and
      timolol. As with abortive therapy, costs vary widely among these prophylactic
      agents. A novel approach to migraine prophylaxis is injection of botulinum toxin.
      A cost-analysis model is presented to show the impact of utilizing botulinum
      toxin in a large managed care system.

PMID- 16095270
TI  - Migraine in the managed care environment.
AB  - Migraine headache remains a major clinical problem in the managed care
      environment, incurring a heavy toll in terms of treatment costs, patient
      disability, and patient quality of life. Abortive treatment with triptans has
      become the standard of care in patients with acute episodic migraine. However,
      there is no such consensus about the optimal approach to prophylaxis in patients
      with frequent or intractable migraine. The agents currently approved in this role
      are not always effective and may cause systemic side effects. One potential
      alternative to currently approved treatments may be botulinum toxin. When
      injected into carefully pinpointed pericranial locations at 3-month intervals,
      botulinum toxin may offer effective prophylaxis with minimal side effects.
      However, the evidence available to date has been inconsistent, with benefit seen
      in some reports but not in others. Consequently, managed care policymakers have
      been cautious about approval of coverage for this treatment. Specific criteria
      for the use of botulinum toxin vary among different plans. At present, many plans
      do not approve coverage for this agent for the treatment of migraine; other plans
      do allow coverage as needed for patients in whom conventional approaches have
      been ineffective or intolerable, but not as a first-line approach to prophylaxis.

PMID- 16095271
TI  - Determination of the absolute configuration of flexible molecules by ab initio
      ORD calculations: a case study with cytoxazones and isocytoxazones.
AB  - Ab initio calculations of the optical rotatory power of the natural cytokine
      modulator cytoxazone 1 and its trans-diastereomer 2, as well as the structural
      isomers cis-3 and trans-4 isocytoxazones, have been performed at four different
      wavelengths (589, 546, 435, and 405 nm) by Density Functional Theory. The
      calculation of ORD curves provides a reliable method for the assignment of
      absolute configuration of these conformationally flexible molecules. The absolute
      configurations of isocytoxazones has been established as (+)-(4R,5S)-cis-3 and
      (+)-(4S,5S)-trans-4.

PMID- 16095272
TI  - Conformational thermodynamic and kinetic parameters of methyl-substituted 1,3
      butadienes.
AB  - The s-trans/s-cis conformational equilibria of 10 methyl-substituted 1,3
      butadienes [(E)- and (Z)-1,3-pentadiene; 2-methyl-1,3-butadiene; (E)-2-methyl-1,3
      pentadiene; 2,3-dimethyl-1,3-butadiene; (E,E)-, (E,Z)-, and (Z,Z)-2,4-hexadiene;
      2,5-dimethyl-2,4-hexadiene; and (E,E)-2,4-dimethyl-2,4-hexadiene] were explored
      by trapping high-temperature conformational equilibria by cryogenic deposition.
      The vapor state enthalpy differences of these s-trans/s-cis conformers, DeltaH(t
      equilibrium c), were determined by varying the equilibrating temperature and
      integrating the resulting matrix isolated IR spectra. The results obtained are in
      good agreement with ab initio calculations at the G3 level. From these
      thermodynamic parameters, methyl group nonbonded interactions in conjugated 1,3
      butadienes were delineated. Rates of decay of s-cis conformers to their s-trans
      rotamers were obtained in the solid-state by warming up trapped high-temperature
      equilibrated samples formed from neat depositions. These data were analyzed in
      terms of dispersive kinetics with matrix site effects in the solid-state modeled
      by a Gaussian distribution of activation energies. The activation barriers thus
      obtained were compared with G3 calculations of the enthalpies of activation.

PMID- 16095273
TI  - A tetrameric sugar-based azobenzene that gels water at various pH values and in
      the presence of salts.
AB  - A novel low-molecular mass tetrameric sugar derivative containing azobenzene
      core, 1, showed pronounced hydrogelation at micromolar concentration. Based on
      this observation, four related azobenzene based tetrameric sugar derivatives, 4
      7, and three tetrameric sugar derivatives with a bis-terephthalamide core, 9-11,
      were also synthesized. However, none of these closely related analogues of the
      compound 1 showed effective gelation. The gel formed from 1 was characterized
      extensively using melting temperature analysis, UV-vis, FT-IR, circular dichroism
      spectroscopy, and scanning electron microscopy. The resultant gel exhibited
      impressive tolerance to the pH variation of the aqueous phase and gelated water
      in the pH range of 4-10. While UV-vis and CD spectroscopy indicated that
      pronounced aggregation of the azobenzene chromophores in 1 was responsible for
      gelation, FT-IR studies showed that hydrogen bonding is also a contributing
      factor in the gelation process. The melting of gel was found to depend on the pH
      of the aqueous medium in which gel was formed. The gel showed considerable
      photostability to UV irradiation, indicating tight intermolecular packing inside
      the gelated state that rendered azobenzene groups in the resultant aggregate
      refractory to photoisomerization. The electron micrographs of the aqueous gels of
      1 showed the existence of spongy globular aggregates in such gelated materials.
      Addition of salts to the aqueous medium led to a delay in the gelation process
      and also caused remarkable morphological changes in the microstructure of the
      gel.

PMID- 16095274
TI  - Phenylene alkylene dendrons with site-specific incorporated fluorescent pyrene
      probes.
AB  - This report deals with the synthesis and the spectroscopic properties of two
      second generation (G2) dendrons with site-specific incorporated phenyl pyrene
      derivatives as solvatochromic fluorescent probes. The generations that do not
      carry the probe are equipped with volume dummies, pyrene moieties that do not
      show a solvatochromic effect. Two complementary G2 phenylene alkylene dendrons
      were synthesized using Suzuki-Miyaura cross coupling. Most of the reactions used
      in the 10-step sequence generating the target compounds proceeded in good yields.
      The incorporated probes can be selectively photoexcited and show solvatochromic
      shifts that are of the same magnitude as for the free probes in a homogeneous
      solvent environment. In addition to the charge-transfer fluorescence, a broad
      emission band is observed that is assigned to an intramolecular exciplex
      formation between the aryl pyrene chromophores.

PMID- 16095275
TI  - The interplay of thio(seleno)amide/vinylogous thio(seleno)amide "resonance" and
      the anisotropic effect of thiocarbonyl and selenocarbonyl functional groups.
AB  - Amino-substituted thio(seleno)acrylamides 1-4 were synthesized and their 1H and
      13C NMR spectra assigned. Both the NMR data and the results of theoretical
      calculations at the ab initio level of theory were employed to elucidate the
      adopted structures of the compounds in terms of E/Z isomerism and s-cis/s-trans
      configuration. In the case of the asymmetrically N(Me)Ph-substituted compounds,
      ab initio GIAO-calculated ring current effects of the N-phenyl group were applied
      to successfully determine the preferred conformer bias. The restricted rotations
      about the two C-N partial double bonds were studied by DNMR and the barriers to
      rotation (DeltaG(c)++) determined at the coalescence temperatures, and these were
      discussed with respect to the structural differences between the compounds. The
      barriers to rotation were also calculated at the ab initio level of theory where
      the best results (R(2) = 0.8746) were obtained only with inclusion of the solvent
      at the SCIPCM-HF/6-31G* level of theory. The calculations also provided means of
      assessing structural influences which were not available due to inaccessible
      rotation barriers. By means of natural bond orbital (NBO) analysis of 1-4, the
      occupation numbers of nitrogen lone pairs and bonding/antibonding pi/pi orbitals
      were shown to quantitatively describe thio(seleno)amide/vinylogous
      thio(seleno)amide "resonance". Finally, the thio(seleno)carbonyl anisotropic
      effect was quantitatively calculated by the GIAO method and visualized by
      isochemical shielding surfaces (ICSS). Only marginal differences between the two
      anisotropic effects were calculated and are therefore of questionable utility for
      previous and future applications with respect to stereochemical assignments.

PMID- 16095276
TI  - Preparation, structure, and anion sensing properties of 1,n
      diaza[n]ferrocenophanes.
AB  - The synthesis of structurally new types of azaferrocenophanes is reported in this
      note: 4, which comprises a 1,2-fused azaheterocycle to a 1,3
      diaza[3]ferrocenophane framework; 1,3-diaza[3]ferrocenophanes 5 and 7, which can
      be considered as a 1,1'-ferrocenylene N,N'-guanidine or urea, respectively; and
      1,3,6,8-tetraza[8]ferrocenophanes 9 and 10, bearing two ureido moieties in the
      ansa-bridge. These compounds were prepared directly from 1,1'
      bis(isocyanato)ferrocene 1 and thoroughly characterized by spectroscopic means.
      Tetraza[8]ferrocenophanes 9 and 10 show spectral and electrochemical anion
      sensing action: they display a selective downfield shift of the urea protons and
      a cathodic shift of the ferrocene/ferrocinium redox couple with
      dihydrogenphosphate and fluoride anions. The crystal structure of compound 4 has
      been determined by single-crystal X-ray methods.

PMID- 16095277
TI  - Generation and characterization of the selenocysteinyl radical: direct evidence
      from time-resolved UV/Vis, electron paramagnetic resonance, and Fourier transform
      infrared spectroscopy.
AB  - The selenocysteinyl radical 1 has been generated for the first time by laser
      flash photolysis (lambda(exc) = 266 nm) of dimethyl bis(N-tert-butoxycarbonyl)-l
      selenocystine 2 and of [(9-fluorenylideneamino)oxycarbonyl]methyl(N-tert
      butoxycarbonyl)-l-selenocysteine 3 in acetonitrile and characterized by time
      resolved (TR) UV/Vis, Fourier transform infrared (FTIR), and electron
      paramagnetic spectroscopy in combination with theoretical methods. A detailed
      product study was conducted using gas chromatography and one- and two-dimensional
      NMR spectroscopy. In the case of [(9-fluorenylideneamino)oxycarbonyl]methyl(N
      tert-butoxycarbonyl)-l-selenocysteine 3, the (9-fluorenylideneamino)oxycarbonyl
      moiety serves as a photolabile protection group providing a "caged
      selenocysteinyl radical" suitable for biophysical applications. Cleavage of the
      diselenide bridge or the selenium-carbonyl bond by irradiation is possible in
      high quantum yields. Because of the lack of a good IR chromophore in the mid-IR
      region, the selenocysteinyl radical 1 cannot be monitored directly by TR FTIR
      spectroscopy. TR UV/Vis spectroscopy revealed the formation of the
      selenocysteinyl radical 1 from both precursors. The selenocysteinyl radical 1 has
      a lifetime tau approximately 63 mus and exhibits a strong band located at
      lambda(max) = 335 nm. Calculated UV absorptions of the selenocysteinyl radical
      (UB3LYP/6-311G(d,p)) are in good agreement with the experimental results. The use
      of TR UV/Vis spectroscopy permitted the determination of the decay rates of the
      selenocysteinyl radical in the presence of two quenchers. The product studies
      demonstrated the reversible photoreaction of dimethyl bis(N-tert-butoxycarbonyl)
      l-selenocystine 2. Products of the photolysis of the "caged selenocysteinyl
      radical" precursor 3 are dimethyl bis(N-tert-butoxycarbonyl)-l-selenocystine 2,
      carbon dioxide, and some further smaller fragments. In addition, the
      photodecomposition of the (9-fluorenylideneamino)oxycarbonyl moiety produced 9
      fluorenone-oxime 4, 9-fluoren-imine 5, and 6 and 7 as products of the
      dimerization of two 9-fluorenoneiminoxy radicals 8.

PMID- 16095278
TI  - Self-assembly, binding, and dynamic properties of heterodimeric porphyrin
      macrocycles.
AB  - A series of heterodimeric tetralactam macrocycles have been self-assembled using
      two kinetically labile zinc porphyrin-pyridine interactions. The stability
      constants have been determined by UV-vis titrations in CHCl3. The stability
      constants depend on the degree of preorganization of the linker units connecting
      the interacting groups. The ability of the self-assembled macrocycles to bind a
      terephthalamide guest was also investigated. One of the macrocycles was used for
      the construction of a [2]rotaxane. The dynamic properties of this system provide
      insight into the exchange mechanisms that operate in complex noncovalent
      assemblies.

PMID- 16095279
TI  - Ruthenium-complex-catalyzed regio- and stereoselective linear codimerization of 2
      norbornenes with acrylic compounds.
AB  - A linear codimerization of 2-norbornenes with acrylic compounds such as acrylates
      and an acrylamide proceeded efficiently by ruthenium catalyst systems,
      RuCl3(tpy)/Zn (tpy = 2,2':6',2' '-terpyridine) or [RuCl2(C6H6)]2/Zn in a primary
      or secondary alcoholic solvent, to afford the corresponding exo-trans-2
      norbornylacrylates as major products regio- and stereoselectively along with a
      small amount of cis isomers. The reaction of 2,5-norbornadiene with methyl
      acrylate also gave the linear exo-trans codimer, which was effectively catalyzed
      by the addition of triarylphosphines to the RuCl3(tpy)/Zn catalyst system.

PMID- 16095280
TI  - N-Vinyl- and C-vinylpyrroles from azafulvenium methides. flash vacuum pyrolysis
      route to 5-Oxo-5H-pyrrolizines and 1-azabenzo[f]azulenes.
AB  - 1-Azafulvenium methides, generated from pyrrolo[1,2-c]thiazole-2,2-dioxides'
      thermal extrusion of sulfur dioxide, led to the synthesis of functionalized
      pyrroles. The intramolecular trapping of these transient 8pi 1,7-dipoles in
      pericyclic reactions, namely sigmatropic [1,8]H shifts and 1,7
      electrocyclization, allowed the synthesis of N-vinylpyrroles and C-vinylpyrroles
      which, under flash vacuum pyrolysis conditions, are converted into 5-oxo-5H
      pyrrolizines or 4-oxo-1,4-dihydro-1-aza-benzo[f]azulenes, respectively. These
      heterocycles can also be obtained directly from FVP of pyrrolo[1,2-c]thiazole 2,2
      dioxides. The synthesis and X-ray structure of a new 6-oxocyclopenta[b]pyrrole
      derivative is also reported.

PMID- 16095281
TI  - Stereoselectivity and substrate specificity in the kinetic resolution of methyl
      substituted 1-oxaspiro[2.5]octanes by Rhodotorula glutinis epoxide hydrolase.
AB  - The kinetic resolution of a range of methyl-substituted 1-oxaspiro[2.5]octanes by
      yeast epoxide hydrolase (YEH) from Rhodotorula glutinis has been investigated.
      The structural determinants of substrate specificity and stereoselectivity of YEH
      toward these substrates appeared to be the configuration of the epoxide ring and
      the substitution pattern of the cyclohexane ring. For all compounds tested, O
      axial epoxides were hydrolyzed faster than the corresponding O-equatorial
      compounds. In concern of the ring substituents, YEH preferred methyl groups on
      the Re side of the ring. Placement of substituents close to the spiroepoxide
      carbon decreased the reaction rate but increased enantioselectivity. YEH
      catalyzed kinetic resolutions of 4-methyl 1-oxaspiro[2.5]octane epimers were most
      enantioselective (E > 100).

PMID- 16095282
TI  - Synthesis of indeno-fused derivatives of quinolizinium salts, imidazo[1,2
      a]pyridine, pyrido[1,2-a]indole, and 4h-quinolizin-4-one via benzannulated enyne
      allenes.
AB  - The benzannulated enediynyl propargylic alcohol 8 was prepared from 1-bromo-2
      iodobenzene by two consecutive Sonogashira cross-coupling reactions. The
      subsequent transformation to mesylate 9 followed by treatment with 4-substituted
      pyridines 10 then furnished the benzannulated enediynes 11. On exposure of 11 to
      triethylamine, the indeno-fused quinolizinium salts 15 were produced in
      quantitative yield. Presumably the reaction proceeded through a 1,3-prototropic
      rearrangement to form the benzannulated enyne-allenes 12, which then underwent
      either a concerted Diels-Alder reaction or a two-step process involving a
      Schmittel cyclization reaction to form biradical 13 followed by an intramolecular
      radical-radical coupling to afford 14. A subsequent prototropic rearrangement
      then produced 15. Similarly, 21a and 21b were produced from 19a and 19b,
      respectively. The use of the Sonogashira reaction for cross-coupling between 1
      iodo-2-(phenylethynyl)benzene (7) and 1-(2-propynyl)-1H-imidazole (25) followed
      by treatment of the resulting adduct with potassium tert-butoxide gave the indeno
      fused imidazo[1,2-a]pyridine 24 in 98% yield. Similarly, the indeno-fused
      pyrido[1,2-a]indole 32 and 4H-quinolizin-4-one 35 were obtained by starting from
      7 for cross-coupling with 1-(2-propynyl)-1H-indole (30) and 1-(2-propynyl)-2(1H)
      pyridinone (33), respectively, followed by treatment with potassium tert
      butoxide.

PMID- 16095283
TI  - Diastereoselective intermolecular radical addition to nitrones.
AB  - The intermolecular radical addition to chiral nitrones 2, 4, 5, and 16 was
      studied. The isopropyl radical addition to Oppolzer's camphorsultam derivative 2
      of glyoxylic nitrone proceeded with excellent diastereoselectivity to give the
      desired isopropylated product 3a accompanied by the diisopropylated product 3b. A
      high degree of stereocontrol in the reaction of cyclic nitrone 4 was achieved.
      The ethyl radical addition to nitrone 4 with triethylborane afforded the desired
      ethylated product 9a accompanied by the diethylated product 10a and the ethylated
      nitrone 11a. To evaluate the utility of cyclic nitrone 4, several alkyl radicals
      were employed in the addition reaction, which afforded the alkylated products 9b
      d with excellent diastereoselectivities. In the presence of Mg(ClO(4))(2), the
      ethyl radical addition to BIGN 16 afforded selectively syn isomers. In contrast,
      the alkyl radical addition to 16 took place even in the absence of Lewis acid to
      give anti isomers.

PMID- 16095284
TI  - Efficient emission from charge recombination during the pulse radiolysis of
      electrochemical luminescent donor-acceptor molecules with an ethynyl linkage.
AB  - Efficient monomer and excimer emission from various donor-acceptor substituted
      phenylethynes (PE), which are known as efficient electrogenerated
      chemiluminescent molecules, was observed with time-resolved fluorescence
      measurement during the pulse radiolysis in benzene. On the basis of the transient
      absorption and emission measurements, and steady-state measurements, the
      formation of PE in the singlet excited state (1PE*) and the excimer (1PE2*) can
      be interpreted by the charge recombination between the PE radical cation (PE.+)
      and the PE radical anion (PE.-) which are generated initially from the radiolytic
      reaction in benzene. It is suggested that the positive and negative charges are
      localized on the donor and acceptor moieties in the radical cation and anion,
      respectively. This mechanism is reasonably explained by the relationship between
      the annihilation enthalpy changes (-DeltaH' degrees ) and singlet excitation
      energies of donor-substituted phenyl(9-acridinyl)ethynes (1(a-e)). In addition to
      the monomer emission, the compounds bearing weak donors (1(a-d)) show the excimer
      emission due to a very small twist angle between the donor and acceptor moieties.
      For the phenyl(9-cyano-10-anthracenyl)ethynes (2(c) and 2(f)), although they also
      show the monomer and excimer emissions, it cannot be explained by the
      relationship between -DeltaH' degrees values and their singlet excitation
      energies, suggesting the formation of the ICT state and H-type excimer in which
      two 9-cyano-10-anthracenyl moieties are stacked face-to-face with donor bearing a
      benzene ring projecting perpendicularly away from each other through the charge
      recombination between 2.+) and 2.-) and/or triplet-triplet annihilation.

PMID- 16095285
TI  - Synthesis of isocoumarins and alpha-pyrones via tandem Stille
      reaction/heterocyclization.
AB  - A general route to alpha-pyrones and 3-substituted isocoumarins from (Z)
      iodovinylic acids 1a-f or 2-iodobenzoic acids 4a-c is described, including
      compounds bearing a substituent on the aromatic ring. Treatment of (Z)-beta
      iodovinylic acids 1a-f or 2-iodobenzoic acids 4a-c with various
      allenyltributyltin reagents in the presence of palladium acetate,
      triphenylphosphine, and tetrabutylammonium bromide in dimethylformamide provided
      good yields of the corresponding alpha-pyrones 3a-k or 3-substituted isocoumarins
      5a-g via tandem Stille reaction and 6-endo-dig oxacyclization.

PMID- 16095286
TI  - Novel synthesis of nucleoside 5'-phosphoramidates through reaction of nucleoside
      triphosphates with amines mediated by trimethylsilyl chloride.
AB  - Reaction of nucleoside triphosphates (NTPs) with amines in pyridine mediated by
      trimethylsilyl chloride produced nucleoside 5'-phosphoramidates in moderate
      yields without any preprotection of nucleosides and amino acid methyl esters. The
      reaction pathway is very similar to the mechanism of the RNA capping reaction,
      DNA or RNA ligation reaction, and catalysis of hydrolases and nucleases involving
      the formation of covalent enzyme-NMP (nucleoside 5'-monophosphate) intermediates
      in biological systems, which could provide a valuable clue for the enzymatic
      reactions.

PMID- 16095287
TI  - Lewis acid-catalyzed tandem Diels-Alder reaction/retro-Claisen rearrangement as
      an equivalent of the inverse electron demand hetero Diels-Alder reaction.
AB  - A highly stereoselective formal inverse electron demand hetero Diels-Alder
      reaction (HDA) occurs on reaction of 2-aryl-alpha,beta-unsaturated aldehydes with
      cyclopentadiene. The major pathway for this transformation is shown to be a Lewis
      acid-catalyzed tandem Diels-Alder reaction/retro-Claisen rearrangement.

PMID- 16095288
TI  - Synthesis of nonproteinogenic amino acids to probe lantibiotic biosynthesis.
AB  - The synthesis of six nonproteinogenic amino acids appropriately protected for
      Fmoc-based solid-phase peptide synthesis is described. These amino acids are
      (2S,3R)-vinylthreonine, (2S)-(E)-2-amino-5-fluoro-pent-3-enoic acid
      (fluoroallylglycine), (S)-beta(2)-homoserine, (S) and (R)-beta(3)-homocysteine,
      and (2R,3R)-methylcysteine. Once incorporated into peptides, these compounds were
      envisioned to serve as alternative substrates for the lantibiotic synthases that
      dehydrate serine and threonine residues in their peptide substrates and catalyze
      the subsequent intramolecular Michael-type addition of cysteines to the
      dehydroamino acids.

PMID- 16095289
TI  - Planar and pyramidal tetracoordinate carbon in organoboron compounds.
AB  - Using previously proposed C(BH)2(CH)2 (16, 17) and C(CH)2B2 (22) systems with a
      central planar tetracoordinate carbon (ptC) atom linking two three-membered rings
      as building blocks, a series of stable structures containing two and three ptC
      centers within a molecule have been designed and computationally studied with the
      DFT (B3LYP/6-311+G) method. Inclusion of a carbon atom ligated with pi-accepting
      and sigma-donating boron centers into at least one aromatic ring is critical for
      stabilization of a planar structure. A square pyramidal configuration at
      tetracoordinate carbon may be achieved in appropriately strained molecules such
      as [3.3.3.3]tetraborafenestrane 45 and others by surrounding the carbon with
      boron-centered ligands.

PMID- 16095290
TI  - Irradiation of imine-group VI carbene complexes in the presence of alkynes. 2.
      Control of product distribution.
AB  - The photoreactivity of iminecarbene complexes in the presence of alkynes has been
      explored. Up to four different reaction paths are available depending on the
      alkyne and carbene complex substituents, although in each case only one type of
      product is isolated. 2H-Pyrrole derivatives are formed mainly from aryl alkynes.
      When alkyl alkynes are used, the method affords a new type of aza-dendralene
      product in good yields. Isoquinoline derivatives can also be formed in a two-step
      one-pot photochemical process when the appropriate substituents are present.
      Finally, indene derivatives are also available through a benzannulation reaction.
      To explore the underlying mechanism, we carried out computations using DFT
      methods. Experimental and theoretical results compare well, which allows control
      over the reaction and product distribution.

PMID- 16095291
TI  - Polymer-supported N-heterocyclic carbene-palladium complex for heterogeneous
      Suzuki cross-coupling reaction.
AB  - Poly(1-methylimidazoliummethyl styrene)-surface grafted-poly(styrene) resin was
      prepared for the first time as a polymer-supported N-heterocyclic carbene (NHC)
      precursor for palladium complex by suspension polymerization. To prepare this
      polymer-supported NHC precursor, 1-methyl-3-(4-vinylbenzyl)imidazolium
      hexafluorophosphate, [MVBIM][PF6-], was synthesized as a monomer and
      copolymerized with styrene and DVB in water. This polymer-supported NHC precursor
      with imidazolium as a ligand, which exists solely on the surface of the resin,
      was well characterized by FE-SEM, CLSM, and IR spectroscopy. The precursor
      containing imidazolium readily formed a stable complex with Pd(OAc)2, and this
      polymer-supported N-heterocyclic carbene-palladium complex exhibited excellent
      catalytic activity for Suzuki cross-coupling reaction in an aqueous medium. The
      catalyst was recovered quantitatively from the reaction mixture by simple
      filtration and was able to be reused for a number of recycles with consistent
      activity in all of the coupling reactions.

PMID- 16095292
TI  - Total synthesis of N-malayamycin A and related bicyclic purine and pyrimidine
      nucleosides.
AB  - Methods are described for the total synthesis of bicyclic perhydrofuropyran
      nucleosides as N-analogues of the naturally occurring malayamycin A. Formation of
      the N-nucleosides relied on the activation of thioglycosides, proceeding via
      sulfonium intermediates. Ring closure metathesis was used in two approaches to
      build the bicyclic dioxa heterocycle. Another approach relied on the use of a
      sugar precursor and cyclization to the bicyclic thioglycoside.

PMID- 16095293
TI  - Stereoselective synthesis of constrained oxacyclic hydroxyethylene isosteres of
      aspartic protease inhibitors: aldol and Mukaiyama aldol methodologies for
      branched tetrahydrofuran 2-carboxylic acids.
AB  - The synthesis of diastereomeric 3-substituted-tetrahydrofuran 2-carboxylic acids
      in enantiopure form was achieved relying on aldol condensations of N-substituted
      alpha-amino aldehydes with enolates and enol silyl ethers of gamma-butyrolactone.
      Catalytic YbFOD leads to a high yield of a syn/syn-alpha-amino alcohol isomer.
      This was used as a constrained THF subunit in the synthesis of a peptidomimetic
      intended as an inhibitor of the enzyme BACE1, which is implicated in the cascade
      of events leading to plaque formation in Alzheimer's disease.

PMID- 16095294
TI  - Stereoselective synthesis of constrained azacyclic hydroxyethylene isosteres as
      aspartic protease inhibitors: dipolar cycloaddition and related methodologies
      toward branched pyrrolidine and pyrrolidinone carboxylic acids.
AB  - The synthesis of three vicinally substituted azacyclic carboxylic acids in
      enantiopure form was achieved from a common alpha-amino aldehyde originating from
      l-leucine. Pyrrolidines and pyrrolidinones were elaborated from alpha,beta
      unsaturated gamma-hydroxy-delta-amino acids via azomethine ylide 1,3-dipolar
      addition and conjugate addition/cyclization strategies, respectively. The
      azacyclic amino acids were incorporated in a pseudopeptide now encompassing a
      hydroxyethylene isostere. Low nanomolar inhibition of BACE1, an enzyme implicated
      in the cascade of events leading to plaque formation in Alzheimer's disease, was
      found with a pyrrolidinone analogue.

PMID- 16095295
TI  - A stereoselective synthesis of phosphinic acid phosphapeptides corresponding to
      glutamyl-gamma-glutamate and incorporation into potent inhibitors of folylpoly
      gamma-glutamyl synthetase.
AB  - Radical addition of H3PO2 to N-/C-protected vinyl glycine led to the
      corresponding H-phosphinic acid in excellent yield. The non-nucleophilic H
      phosphinic acid was converted to a nucleophilic P(III) species, RP(OTMS)2, which
      was used in two approaches to the target phosphinic acid containing
      pseudopeptide. New methodology was developed that led to excellent yields in the
      reaction of RP(OTMS)2 with unactivated electrophiles, including an acyclic
      homoallylic bromide. However, en route to the target pseudopeptide, Arbuzov
      reaction of RP(OTMS)2 with a cyclic homoallylic bromide, (R)-3-(bromomethyl)
      cyclopent-1-ene, led to a rearranged allylic phosphinic acid rather than the
      desired homoallylic derivative, a putative glutarate surrogate. Conjugate
      addition of RP(OTMS)2 to alpha-methylene glutarate containing a chiral auxiliary
      resulted in only modest diastereoselectivity. Purification by flash
      chromatography provided protected derivatives of both diastereomers of the
      pseudopeptide. Following global deprotection, coupling of (S)-H-Glu-gamma
      [Psi(P(O)(OH)(CH2))]-(S)-Glu-OH and (S)-H-Glu-gamma-[Psi(P(O)(OH)(CH2))]-(R)-Glu
      OH to (4-amino-4-deoxy-10-methyl)pteroyl azide led to the target compounds for
      biochemical study as inhibitors of the ATP-dependent ligase, folylpoly-gamma
      glutamate synthetase.

PMID- 16095296
TI  - Annulation of aromatic imines via directed C-H bond activation.
AB  - A directed C-H bond activation approach to the synthesis of indans, tetralins,
      dihydrofurans, dihydroindoles, and other polycyclic aromatic compounds is
      presented. Cyclization of aromatic ketimines and aldimines containing alkenyl
      groups tethered at the meta position relative to the imine directing group has
      been achieved using (PPh3)3RhCl (Wilkinson's catalyst). The cyclization of a
      range of aromatic ketimines and aldimines provides bi- and tricyclic ring systems
      with good regioselectivity. Different ring sizes and substitution patterns can be
      accessed through the coupling of monosubstituted, 1,1- or 1,2-disubstituted, and
      trisubstituted alkenes bearing both electron-rich and electron-deficient
      functionality.

PMID- 16095297
TI  - A convenient entry to C2- and C3-substituted gulono-gamma-lactone derivatives
      from L-ascorbic acid.
AB  - A convenient method to obtain unknown chiral C2- and C3-functionalized aldono-1,4
      lactone derivatives starting from l-ascorbic acid, which would be valuable in the
      synthesis of derivatives of various pharmacologically active agents for structure
      activity studies, is described. The practicality of this approach is demonstrated
      by the synthesis of a series of 5,6-O-isopropylidene-2-allyl-3-keto-l-galactono
      gamma-lactone and 5,6-O-isopropylidene-3-allyl-2-keto-l-galactono-gamma-lactone
      derivatives using the thermal Claisen rearrangement of the corresponding 3-O- and
      2-O-allyl derivatives of 5,6-O-isopropylidene-l-ascorbic acid, respectively,
      followed by stereospecific reduction to the corresponding alcohols. The synthetic
      steps are shown to be efficient, and enantiospecific, and they proceed with high
      yields.

PMID- 16095298
TI  - Nitrosation chemistry of pyrroline, 2-imidazoline, and 2-oxazoline: theoretical
      Curtin-Hammett analysis of retro-ene and solvent-assisted C-X cleavage reactions
      of alpha-hydroxy-N-nitrosamines.
AB  - The results are presented of a theoretical study of the nitrosation chemistry of
      pyrroline 1 (X = CH2), imidazoline 2 (X = NH), and 2-oxazoline 3 (X = O). Imines
      1-3 are converted to the alpha-hydroxy-N-nitrosamines 7-9 via the N
      nitrosoiminium ions 4-6. The NN-cis isomers of 7-9 may undergo retro-ene
      reactions to the delta-oxoalkyl diazotic acids 10-12. With the opportunity for
      microsolvation, C-X cleavage becomes possible for 8 and 9 and leads to the
      formation of N-(2-aminoethyl)- and N-(2-hydroxyethyl)-N-nitrosoformamides 15 and
      16, respectively. The NN-isomerization barriers are comparable to the barriers
      for the ring-opening reactions, and the consideration of two Curtin-Hammett
      scenarios is required: CH-I for the NN-trans-rotamers of 7-9 to undergo C-X
      cleavage or NN-isomerization and CH-II for the NN-cis-rotamers to undergo C-X
      cleavage, C-N cleavage, or NN-isomerization. We determined all stereoisomers of
      the substrates, the products, and of all transition states structures for the
      retro-ene reactions of 7-9, the C-X cleavages of microsolvated 8 and 9, and the
      NN-isomerizations of 8 and 9. The potential energy surfaces were explored at the
      B3LYP/6-31G level, and the results are discussed with emphasis on the comparison
      of the kinetics and thermodynamics of C-N versus C-X cleavage. The study shows
      all decompositions to be very fast with activation barriers below 21 kcal.mol(
      1), and the comparative analysis predicts that the chemical toxicologies of 1 and
      3 should be similar and remarkably different from that of 2.

PMID- 16095299
TI  - Controlled synthesis of multinuclear metal complex arrays by cross coupling of
      coordinated ligands.
AB  - Conditions for efficient cross linking of chelating organic ligands within
      different metal-containing building blocks have been developed, allowing the
      preparation of heteronuclear Ru/Os complexes in a controlled manner. Critical to
      the success of this protocol is the introduction of an Os center early in the
      synthesis and the use of CuI under polar conditions. Noteworthy features of this
      method are the tolerance of the metal centers in both reaction partners and the
      absence of any metal scrambling during the C-C formation or ultimate complexation
      procedures.

PMID- 16095300
TI  - Chain amplification in photoreactions of N-alkoxypyridinium salts with alcohols:
      mechanism and kinetics.
AB  - Photosensitized electron transfer from a variety of singlet- and triplet-excited
      donors to N-methoxypyridinium salts leads to N-O bond cleavage. Hydrogen atom
      abstraction by the resulting methoxy radical from an added alcohol generates an
      alpha-hydroxy radical that reduces another pyridinium molecule, thus leading to
      chain propagation. For example, thioxanthone-sensitized reactions of 4-cyano-N
      methoxypyridinium, P1, with several aliphatic and benzyl alcohols gave quantum
      yields for products formation (an aldehyde or a ketone and protonated 4
      cyanopyridinium) of approximately 15-20, at reactant concentrations of
      approximately 0.02-0.04 M. The reaction can also be sensitized with triplet
      benzopheone, which in this case acts as an electron donor. Energetic limitations
      on chain propagation are imposed by the relationship between the oxidation
      potential of the alpha-hydroxy radical and the reduction potential of the
      pyridinium salt. The chain reactions proceed despite approximately 0.25 eV
      endothermicity for the electron-transfer step. Chain reactions with the harder-to
      reduce 4-phenyl-N-methoxypyridinium, however, are limited in scope because of
      increased endothermicity for electron transfer. The thioxanthone-sensitized
      reaction of P1 with benzhydrol was studied in detail by a combination of steady
      state and transient kinetics. The bimolecular rate constants for the chain
      propagation reactions:hydrogen atom abstraction by the methoxy radical and
      electron transfer from the diphenylketyl radical to P1 are approximately 6 x
      10(6) and 1.1 x 10(6) M(-1) s(-1), respectively. The kinetic data indicate that
      deuterium atom abstraction by the methoxy radical from the solvent, acetonitrile
      d(3), is a dominant chain-terminating process. Because of a large deuterium
      isotope effect, approximately 7, the quantum amplification is strongly suppressed
      when the reaction is carried out in acetonitrile.

PMID- 16095301
TI  - Structural effects on the beta-scission reaction of tertiary arylcarbinyloxyl
      radicals. The role of alpha-cyclopropyl and alpha-cyclobutyl groups.
AB  - A product and time-resolved kinetic study on the reactivity of tertiary
      arylcarbinyloxyl radicals bearing alpha-cyclopropyl and alpha-cyclobutyl groups
      has been carried out. Both the 1-cyclopropyl-1-phenylethoxyl (1.) and alpha,alpha
      dicyclopropylphenylmethoxyl (2.) radicals undergo beta-scission to give
      cyclopropyl phenyl ketone as the major or exclusive product with rate constants
      higher than that measured for the cumyloxyl radical. It is proposed that in the
      transition state for beta-scission of 1. and 2., formation of the C=O double bond
      is assisted by overlap with the C-C bonding orbitals of the cyclopropane ring.
      With tertiary arylcarbinyloxyl radicals bearing alpha-cyclobutyl groups such as
      the 1-cyclobutyl-1-phenylethoxyl (4.) and 1-cyclobutyl-1-phenylpropoxyl (5.)
      radicals, the fragmentation regioselectivity is essentially governed by the
      stability of the radical formed by beta-scission. Accordingly, 4. undergoes
      exclusive C-cyclobutyl bond cleavage to give acetophenone, whereas with 5.,
      competition between C-cyclobutyl and C-ethyl bond cleavage, leading to
      propiophenone and cyclobutylphenyl ketone in a 2:1 ratio, is observed.

PMID- 16095302
TI  - Asymmetric decarboxylative Claisen rearrangement reactions of sulfoximine
      substituted allylic tosylacetic esters.
AB  - Allylic acetate esters containing a variety of N-arylsulfonyl sulfoximines on the
      acetyl residue have been prepared and submitted to the decarboxylative Claisen
      rearrangement reaction. Rearranged products were isolated in generally good
      yields, and diastereoselectivities up to 82:18 have been obtained. The N-(2,4,6
      triisopropylphenylsulfonyl)-S-phenyl sulfoximine moiety gave the best
      selectivity. The stereochemistry of the major isomer was established by X-ray
      crystallography. A model to explain the stereochemical course of the
      rearrangement is proposed.

PMID- 16095303
TI  - Sequential aminodiene Diels-Alder approach to the ergoline skeleton.
AB  - Through a novel sequence of aminodiene Diels-Alder reactions, several substituted
      amidofurans were readily converted to tricyclic ketones in good yield. The
      formation of the tricyclic ketone system is the result of a ring opening and
      dehydration of a transient oxabicyclic adduct formed by an intramolecular Diels
      Alder cycloaddition of an amidofuran with a cyclohexenone moiety tethered such
      that it participates in the cycloaddition as the 2pi component. A convenient way
      to construct the cyclohexenone is to make use of some aminodiene chemistry
      developed by Rawal. An angular carbomethoxy group is required in order to
      activate the olefin toward cycloaddition with Rawal's diene. The presence of this
      activating group not only prevents the isomerization of the advanced ergoline
      intermediate to a naphthalene but can also be leveraged for an oxidation to
      provide Uhle's ketone (13). The easily formed Kornfeld ketone analogue 25 was
      readily transformed into the corresponding triflate 41 by the action of triflic
      anhydride and a base. Oxidative addition of vinyl triflate 41 to Pd(0) and the
      ability of the resulting vinyl palladium species to undergo cross-coupling with
      terminal alkynes prompted us to devise an expeditious route to lysergic acid.
      Unfortunately, our inability to carry out a regioselective Heck reaction using
      vinyl triflate 41 and the methylene amino acrylate ester 48 thwarted the
      completion of the synthesis of lysergic acid.

PMID- 16095304
TI  - Complete stereochemistry of neamphamide A and absolute configuration of the beta
      methoxytyrosine residue in papuamide B.
AB  - The absolute stereochemistry of the three unresolved structural components in
      neamphamide A (1) was determined to be (R)-beta-methoxy-L-tyrosine, (2R,3R,4S)-4
      amino-7-guanidino-2,3-dihydroxyheptanoic acid, and (2R,3R,4R)-3-hydroxy-2,4,6
      trimethylheptanoic acid. Stereochemical assignments were made by chemical
      degradation of 1, derivatization of the resulting products, and then
      spectroscopic and chromatographic comparison of the derivatives with
      synthetically prepared standards. Using the same analytical protocol developed
      for 1, the beta-methoxytyrosine residue in papuamide B (2) was found to be (R)
      beta-methoxy-D-tyrosine. This represents a rare example of divergent
      stereochemistry in an unusual amino acid residue that is present in two closely
      related classes of peptides.

PMID- 16095305
TI  - Regiocontrolled, palladium-catalyzed bisfunctionalization of allenyl esters.
      Multicomponent coupling approaches to highly substituted alpha,beta-unsaturated
      delta-lactones.
AB  - A palladium-catalyzed regioselective bisfunctionalization of allenyl esters with
      boronic acids (nucleophiles) and aldehydes (electrophiles) was demonstrated. The
      three-component coupling afforded alpha,beta-unsaturated delta-lactones under
      mild conditions and with excellent chemo-, regio-, and diastereoselectivity.
      Aromatic, heteroaromatic and vinylic boronic acids (R1B(OH)2) reacted with ethyl
      2,3-butadienoate and benzaldehyde to afford the corresponding 4-R(1),6-Ph
      disubstituted alpha,beta-unsaturated delta-lactones in 62-78% yields. Lactones
      derived from aromatic, heteroaromatic, and vinylic aldehydes were isolated in 51
      58% yields, while aliphatic aldehydes were less reactive. The regiochemistry of
      bisfunctionalization of allenyl ester homologues remained controlled by the ester
      substituent, and the reactions afforded cis-4,5,6-trisubstituted alpha,beta
      unsaturated delta-lactones and esters of (Z)-syn-3,4,5-trisubstituted-5-hydroxy-2
      pentenoic acids in combined 47-65% yields. The superior performance of a pi
      allylpalladium(II) dimer catalyst featuring an auxiliary allyl ligand derived
      from beta-pinene, among diverse palladium(II) catalysts, was demonstrated. A
      catalytic cycle involving an unsymmetrical bis-pi-allylpalladium complex as the
      key intermediate was proposed, and the communication highlights the synthetic
      potential of such intermediates. However, the efficiency of asymmetry transfer
      remained low (<20%).

PMID- 16095306
TI  - Efficient syntheses of rugulosin analogues.
AB  - Oxidation of 3b or 14c,d with Pb(OAc)4 in AcOH for 20 min at 25 degrees C and 1 h
      at 75 degrees C gave flavoskyrin-type dimers 6b and 15c,d in 53-86% yield.
      Heating a solution of 6b or 15c,d in pyridine under air for 1 h at 75-80 degrees
      C and then for 1-2 h at 110 degrees C afforded rugulosin-type dimers 10b and
      17c,d in 61-88% yield. This two-step sequence provides a practical route to this
      unusual natural product skeleton.

PMID- 16095307
TI  - Oxocarbenium ion cyclizations for C-branched cyclitols: synthesis of a relay
      intermediate for fumagillin analogues.
AB  - A highly stereoselective oxocarbenium ion-alkene cyclization for synthesis of C
      branched cylitols is described. This methodology was applied to 10S, a
      potentially versatile intermediate for side-chain analogues of the antiangiogenic
      agent fumagillin. Compound 10S was subsequently converted to diene 5. Because
      racemic 5 has been converted to racemic fumagillin, this synthesis of 5
      constitutes a formal synthesis of the natural product.

PMID- 16095308
TI  - Silylcuprates from allene and their reaction with alpha,beta-unsaturatedd
      nitriles and imines. Synthesis of silylated oxo compounds leading to cyclopentane
      and cycloheptane ring formation.
AB  - The silylcupration of allenes and the subsequent capture of the intermediate
      cuprate with alpha,beta-unsaturated nitriles is reported. The influence of the
      substitution of the nitrile, the nature of the silylcopper species, and the
      temperature on the selectivity of the reaction is studied. An interesting
      diaddition process was observed (1,2-addition and 1,4-addition), leading to oxo
      compounds which simultaneously have an allylsilane and a vinylsilane group. The
      different reactivity of these two units has been employed in the intramolecular
      allylsilane-terminated cyclization of these adducts, where the vinylsilane moiety
      remains unchanged. To shed some light on the reaction pathway, the behavior of
      alpha,beta-unsaturatedd imines was also checked and a new and convenient way for
      cycloheptane annulation presented. In light of the former results a feasible
      mechanism is proposed.

PMID- 16095309
TI  - An improved approach to chiral cyclopentenone building blocks. Total synthesis of
      pentenomycin I and neplanocin A.
AB  - An improved approach to enantiomerically pure hydroxylated cyclopentenones is
      reported here, which involves intramolecular nitrone cycloaddition of sugar
      derived chiral pent-4-enals and hex-5-en-ones-2 followed by N-O bond cleavage,
      quaternization of the amine thus produced, and finally oxidative elimination of
      the amino group. Synthesis of pentenomycin I and neplanocin A is described
      following this methodology.

PMID- 16095310
TI  - Synthesis of nucleoside analogues bearing the five naturally occurring nucleic
      acid bases built on a 2-oxabicylo[3.1.0]hexane scaffold.
AB  - Hitherto unknown nucleoside analogues incorporating the five naturally occurring
      nucleic acid bases built on a 2-oxabicyclo[3.1.0]hexane template were
      synthesized. The synthesis of these new conformationally restricted nucleoside
      analogues involved the preparation of a suitable sugar precursor bearing the 2
      oxabicyclo[3.1.0]hexane scaffold. This sugar was readily obtained from [(3aS,6aS)
      2,2-dimethyl-3a,6a-dihydrofuro[2,3-d][1,3]dioxol-5-yl]methyl benzyl ether (4)
      following a Simons-Smith-type cyclopropanation reaction. Finally, glycosylation
      reactions and deprotection provided the nucleoside analogues. Using nucleoside 14
      bearing thymine base as a model, we found that the conformation of such
      nucleoside analogue was restricted toward a (0)T(1) conformation.

PMID- 16095311
TI  - A practical asymmetric synthesis of trans-4,5-benzhydrindan-1-ones as a precursor
      of A-nor B-aromatic steroidal compounds.
AB  - The enantio-controlled synthesis of trans-4,5-benzhydrindan-1-ones was achieved
      by means of a stereoselective [4+2] cycloaddition of o-quinodimethanes generated
      by a thermal cleavage of benzocyclobutene derivatives as a key step. The chiral
      substrates of the thermal reaction were synthesized by a diastereoselective
      Grignard addition to the chiral O-isopropylideneglyceroketones connected to a
      benzocyclobutene ring, which were simply prepared from D-mannitol as a chiral
      source. This approach can provide a new efficient access to A-nor B-aromatic
      steroidal compounds.

PMID- 16095312
TI  - Efficient copper-catalyzed N-arylation of sulfoximines with aryl iodides and aryl
      bromides.
AB  - Two simple and inexpensive systems for copper-catalyzed N-arylations of
      sulfoximines with aryl bromides and aryl iodides have been developed. Using 10
      mol % of a copper(I) salt in combination with 20 mol % of a 1,2-diamine and
      Cs2CO3 provides N-arylated sulfoximines in high yields. Various functional groups
      and heteroatoms are tolerated. The method is complementary to the known protocols
      for N-arylations of sulfoximines, which require stoichiometric quantities of
      copper salts or cost-intensive palladium/BINAP catalysts.

PMID- 16095313
TI  - A convenient preparation of xanthene dyes.
AB  - A facile synthetic route utilizing readily available reagents affords a series of
      regioisomerically pure xanthene dye derivatives. Advantages include relatively
      mild conditions and good to excellent yields. Nonpolar, highly crystalline
      intermediates are isolable by standard chromatographic techniques. The
      intermediates are in the requisite xanthene oxidation state, thus avoiding the
      need for relatively inefficient oxidation chemistry and/or harsh conditions.
      During the course of this work, a new boron-mediated 1,2-aryl migration reaction
      was discovered.

PMID- 16095314
TI  - Heteroatom-substituted expanded radialenes: one-pot synthesis and
      characterization of expanded 1,3-dithiolane[n]radialenes.
AB  - The one-pot synthesis, crystal structure, and electronic absorption properties of
      expanded 1,3-dithiolan[5]radialene (6a), the first heteroatom-substituted
      expanded radialene molecule with dithiolanylidene groups as strongly donor
      termini, has been developed. Catalyzed by Ni(PPh3)2Cl2-PdCl2-CuI, radialene 6a
      was assembled by a highly efficient one-pot and protection-free oxidative
      coupling reaction of five alpha-enediyne units starting from the ready available
      alpha,alpha-diethynyl ketene dithioacetal (13) under mild conditions. The crystal
      of 6a, obtained by slow evaporation of DMSO and acetone solutions, shows that the
      inclusion complex of DMSO molecules in the cavity of radialene 6a molecule is
      formed. More importantly, owing to the introduction of the strong electron
      donating alkylthio groups, per(alkylthiolated) expanded radialene 6a shows an
      extremely strong intramolecular push-pull interaction and enhanced macrocyclic
      cross-conjugation.

PMID- 16095315
TI  - An improved synthesis of Fmoc-N-methyl-alpha-amino acids.
AB  - A highly efficient and environmentally more benign synthesis of Fmoc-N-methyl
      alpha-amino acids from the corresponding Fmoc-amino acid, via intermediate 5
      oxazolidinones, has been developed by using Lewis acid catalysis for the
      reductive opening of the oxazolidinone ring.

PMID- 16095316
TI  - Fe(II)-induced reduction of labelled endoperoxides. NMR degradation studies on G3
      factor and its methyl ether.
AB  - The behavior of G3 factor and of its methylated or fluorinated analogues G3Me and
      G3F, was studied under Fe(II) conditions. Degradation products were isolated and
      characterized in each case. The use of labelled compounds allowed us to propose
      mechanisms in which a tertiary radical is involved. This radical rearranges by 5
      exo-trig cyclization, or disproportionates in the case of G3Me. A correlation
      between antiplasmodial activity and stability of this radical is proposed.

PMID- 16095317
TI  - One-step synthesis of O-benzyl hydroxamates from unactivated aliphatic and
      aromatic esters.
AB  - We have developed a simple and high yielding one-step method for the synthesis of
      hydroxamate derivatives directly from a broad range of unactivated esters and the
      anion of O-benzyl-hydroxylamine generated in situ. The reaction takes place in
      minutes at -78 degrees C. Very importantly, the method was successfully employed
      with enolizable esters, including chiral alpha-amino acid esters and peptides,
      with no trace of racemization/epimerization at the alpha carbon detected.

PMID- 16095318
TI  - Diastereoselective synthesis of fulleropyrrolidines from suitably functionalized
      chiral cyclobutanes.
AB  - The first diastereoselective synthesis of fulleropyrrolidines endowed with
      diastereomerically pure functionalized cyclobutanes is reported. The new C(60)
      based cyclobutane derivatives 7a,b and 9 are suitably functionalized for further
      incorporation into peptide surrogates.

PMID- 16095319
TI  - Rapid synthesis of CDP840 with 2-pyrimidyl vinyl sulfide as a platform.
AB  - A rapid synthesis of CDP840 (a potential therapeutic agent for asthma), using 2
      pyrimidyl vinyl sulfide as a platform, has been established. This method includes
      a stereoselective double Mizoroki-Heck-type arylation, a Liebeskind-Srogl-type
      cross-coupling reaction, and a Pd/C-catalyzed hydrogenation.

PMID- 16095320
TI  - Stereoselective route to the ezoaminuroic acid core of the ezomycins.
AB  - Starting from readily available (R)-glycidol, an efficient pathway to a
      strategically functionalized ezoaminuroic acid derivative of the antifungal
      ezomycins has been developed. A key transformation in the synthesis involves
      regio- and stereoselective conversion of the olefinic functionality of a 5,6
      dihydropyran-2-one to the C-2, C-3 trans-1,2-amino alcohol moiety as present in
      ezoaminuroic acid.

PMID- 16095321
TI  - Stannous chloride in alcohol: a one-pot conversion of 2-nitro-N-arylbenzamides to
      2,3-dihydro-1H-quinazoline-4-ones.
AB  - A novel one-step synthesis of 2,3-dihydro-1H-quinazolin-4-ones from 2
      nitrobenzamides is reported. These reactions are mediated by stannous chloride in
      0.02 M methanolic or ethanolic HCl solution and proceed in good yields.

PMID- 16095322
TI  - Zn/CuI-mediated coupling of alkyl halides with vinyl sulfones, vinyl sulfonates,
      and vinyl sulfonamides.
AB  - A novel high-yielding Zn/CuI-mediated coupling method of alkyl halides with vinyl
      sulfones, vinyl sulfonates, and vinyl sulfonamides is described. This protocol is
      applicable for primary, secondary, and tertiary alkyl iodides and bromides. Alkyl
      chlorides and aryl and vinyl halides were unreactive under the reaction
      conditions. Formamide was found to be a superior solvent for obtaining high
      yields.

PMID- 16095323
TI  - Facile synthesis of beta-organotellurobutenolides via electrophilic
      tellurolactonization of alpha-allenoic acids.
AB  - We report a convenient and highly efficient method for the synthesis of beta
      organotellurobutenolides by the aryltellurenyl halides-induced electrophilic
      tellurolactonization of alpha-allenoic acids under mild conditions. The resulting
      beta-organotellurobutenolides can be utilized as precursors for versatile
      butenolide derivatives through a substitution reaction with organocuprate reagent
      or Pd/Cu(I)-catalyzed cross-coupling with terminal alkyne.

PMID- 16095324
TI  - Solvent-dependent, kinetically controlled stereoselective synthesis of 3- and 4
      thioglycosides.
AB  - Facile approaches to prepare 3- and 4-thioglycosides of the galacto, gulo, and
      gluco type from the parent triflates are presented. The dependencies of the
      solvent and the protecting group pattern, as well as the configuration of the
      neighboring and leaving groups, have been studied for these reactions. The
      results clearly show that the efficient stereoselective synthesis of methyl 3
      thio-galactoside depends highly on the solvent and the nucleophile concentration.

PMID- 16095325
TI  - trans-5-aminopipecolyl-aegPNA chimera: design, synthesis, and study of binding
      preferences with DNA/RNA in duplex/triplex mode.
AB  - The design and synthesis of novel chiral PNA monomer based on trans-5
      aminopipecolic acid is reported. The trans diequatorial disposition of the 1,4
      ring substituents in six-membered 5-aminopipecolic acid derivative could be
      favorable over trans 1,3 axial-equatorial disposition in 4-aminopipecolic acid of
      PNA. Studies on the synthesis of trans-4/5-aminopipecolyl PNA-eagPNA chimeras and
      their binding preferences to DNA/RNA in duplex/triplex modes are described.

PMID- 16095326
TI  - Practical synthesis of unsymmetrical ureas from isopropenyl carbamates.
AB  - A very convenient method for the synthesis of unsymmetrical ureas is described,
      based on isopropenyl carbamates. The synthetic efficiency of traditional methods
      for urea formation, such as use of phosgene or alkyl and aryl carbamates, is
      limited by the formation of symmetrical urea side products or reaction
      reversibility. Isopropenyl carbamates react with amines cleanly and irreversibly
      and give unsymmetrical ureas in high yield and purity. This method is ideal for
      the rapid synthesis of compound libraries.

PMID- 16095327
TI  - Synthesis of benzo[b]furans via CuI-catalyzed ring closure.
AB  - A wide variety of benzo[b]furans were synthesized efficiently via a CuI-catalyzed
      ring closure of 2-haloaromatic ketones. The methodology was tolerant to various
      functional groups, affording benzofurans in 72-99% yields.

PMID- 16095328
TI  - Substituent effects on the reactivity of benzo-1,2-dithiolan-3-one 1-oxides and
      their possible application to the synthesis of DNA-targeting drugs.
AB  - The efficiency of polysulfane product generation has been investigated for n
      propyl thiol reactions with ortho- and para-substituted benzo-1,2-dithiolan-3-one
      1-oxides in acetonitrile-water (7:3) mixtures. The reaction is facilitated by
      reducing the electron density at the para position or by placing substituents
      bearing lone pair electrons ortho to the dithiolanone-oxide (S1) reaction center.
      Through-space and through-bond effects both contribute to the conversion of
      polysulfane products.

PMID- 16095329
TI  - Stereoselective synthesis of 3-alkylideneoxindoles via palladium-catalyzed domino
      reactions.
AB  - We have developed efficient catalytic methods for the stereoselective and
      diversity synthesis of various (E)-, (Z)-, and disubstituted 3
      alkylideneoxindoles and 3-alkylidenebenzofuran-2-ones via palladium-catalyzed
      Heck/Suzuki-Miyaura, Heck/Heck, and Heck/carbonylation/Suzuki-Miyaura domino
      reactions.

PMID- 16095330
TI  - The N-cyclopropylimine-1-pyrroline photorearrangement as a synthetic tool: scope
      and limitations.
AB  - The scope and limitations of the photorearrangement of N-cyclopropylimines to 1
      pyrrolines are presented. The influence on the reactivity of different
      substituents throughout the cyclopropane ring and at the iminic position of the N
      cyclopropylimine structure is discussed. The observed effects are interpreted
      from computational studies. The principal findings relate to (1) the enhanced
      reactivity of 1-substituted compounds toward rearrangement, (2) the lack of
      reactivity of crowded cyclopropanes, and (3) the high chemoselectivity of the
      process.

PMID- 16095331
TI  - Palladium-catalyzed one-pot synthesis of highly substituted furans by a three
      component annulation reaction.
AB  - A new three-component cyclization-coupling reaction catalyzed by palladium was
      developed, producing polysubstituted furans in good yields from readily available
      substrates. The reaction conditions and the scope of the process were examined,
      and a possible mechanism is proposed.

PMID- 16095332
TI  - Unexpected, drastic effect of triflic acid on oxidative diacetoxylation of
      iodoarenes by sodium perborate. A facile and efficient one-pot synthesis of
      (diacetoxyiodo)arenes.
AB  - An easy, safe, and effective method for preparing (diacetoxyiodo)arenes from
      iodoarenes is presented. Addition of trifluoromethanesulfonic acid (triflic acid)
      as a promoter causes a drastic increase in the yield of (diacetoxyiodo)arenes in
      the reaction of iodoarenes with sodium perborate. The reaction of the iodoarenes
      with sodium perborate in acetic acid in the presence of triflic acid at 40-45
      degrees C efficiently generates the corresponding (diacetoxyiodo)arenes in high
      yields within short time.

PMID- 16095333
TI  - A new method for conjugation of carbohydrates to proteins using an aminooxy-thiol
      heterobifunctional linker.
AB  - A new, efficient, and mild protocol is presented for the coupling of saccharides
      to proteins. First, a heterobifunctional aminooxy-thiol linker is coupled to the
      bromoacylated protein to introduce aminooxy groups through thioether linkages.
      Condensation of the aminooxylated protein and aldehydo/keto-derivatized
      carbohydrates affords covalent saccharide-protein constructs. Uncoupled
      saccharide can be recovered in its original form. The scope of our protocol is
      exemplified by the coupling of neutral mono- and tetrasaccharides and a
      negatively charged ribitol-phosphate construct to BSA.

PMID- 16095334
TI  - Stereoselective cyclization reactions of IBX-generated alkoxyamidyl radicals.
AB  - In this paper, a method for the generation of alkoxyamidyl radicals is presented.
      These N-centered radicals can efficiently be formed starting from the
      corresponding acylated alkoxyamines using IBX as an oxidant. Stereoselective 5
      exo and 6-exo reactions with these N-heteroatom-centered radicals leading to
      isoxazolidines and [1,2]oxazinanes are discussed. The N-O bond in the
      heterocycles can readily be cleaved with SmI(2) to provide N-acylated 1,3-amino
      alcohols.

PMID- 16095335
TI  - Synthesis of 2,3-di- and 2,3,4-trisubstituted furans from 1,2-dioxines generated
      by an enyne-RCM/Diels-Alder reaction sequence.
AB  - An efficient method for the synthesis of 2,3- and 2,3,4-substituted furans
      starting from acyclic enynes was developed using an enyne-RCM/Diels-Alder
      reaction sequence. The reaction conditions for the transformation of 1,2-dioxines
      having an adjacent 1,2-oxazine ring into furans and the cleavage of N-O bonds are
      discussed.

PMID- 16095336
TI  - A facile Zr-mediated approach to (Z)-enynols and its application to regio- and
      stereoselective synthesis of fully substituted dihydrofurans.
AB  - Efficient synthetic approaches to stereodefined (Z)-enynols have been developed
      through zirconium-mediated cross-coupling reactions of three different components
      involving alkyne, ketone, and alkynyl bromide in a one-pot procedure. The
      subsequent electrophilic cyclization of a wide variety of (Z)-enynols affords
      fully substituted (Z)-5-(1-iodoylidene)-2,5-dihydrofurans with high regio- and
      stereoselectivity under mild reaction conditions.

PMID- 16095337
TI  - A simple continuous flow microwave reactor.
AB  - A new simple procedure for microwave-assisted organic synthesis under continuous
      flow processing has been developed for use in a monomodal microwave synthesizer
      with direct temperature control using the instrument's in-built IR sensor. This
      design makes optimum use of the standing wave cavity to improve the energy
      efficiency of microwave-assisted flow reactions.

PMID- 16095338
TI  - Observation of OD- by microwave spectroscopy.
AB  - For the first time the rotational spectrum of the molecular anion OD- has been
      observed by microwave spectroscopy. OD- has been produced both by a positive and
      negative glow discharge; by investigating the Doppler shift in both cases, the
      unshifted frequency of the J=1<--0 rotational transition has been derived. This
      allowed us to improve the value of the ground-state rotational constant: B(0)=299
      264.940(90) MHz. In order to assess that a negative ion has really been observed,
      the cation N2H+ has been produced and investigated in the same experimental
      conditions.

PMID- 16095339
TI  - Dual-topology/dual-coordinate free-energy simulation using QM/MM force field.
AB  - We have developed a dual-topology/dual-coordinate free-energy simulation method
      for use with a QM/MM force field. By combining two parallel processes into one
      alchemical process, we are able to compute the double free-energy difference
      (delta deltaF) within a single simulation, which eliminates half of the expensive
      quantum-mechanical simulation in general. The method has been tested in computing
      the solvation free-energy differences of several molecular pairs and shows close
      agreement with experimental results.

PMID- 16095340
TI  - Quasirelativistic theory for the magnetic shielding constant. III.
      Quasirelativistic second-order Moller-Plesset perturbation theory and its
      application to tellurium compounds.
AB  - The quasirelativistic (QR) generalized unrestricted Hartree-Fock method for the
      magnetic shielding constant [R. Fukuda, M. Hada, and H. Nakatsuji, J. Chem. Phys.
      118, 1015 (2003); R. Fukuda, M. Hada, and H. Nakatsuji, J. Chem. Phys.118, 1027
      (2003)] has been extended to include the electron correlation effect in the level
      of the second-order Moller-Plesset perturbation theory (MP2). We have implemented
      the energy gradient and finite-perturbation methods to calculate the magnetic
      shielding constant at the QR MP2 level and applied to the magnetic shielding
      constants and the NMR chemical shifts of 125Te nucleus in various tellurium
      compounds. The calculated magnetic shielding constants and NMR chemical shifts
      well reproduced the experimental values. The relations of the chemical shifts
      with the natures of ligands, and the tellurium oxidation states were
      investigated. The chemical shifts in different valence states were explained by
      the paramagnetic shielding and spin-orbit terms. The tellurium 5p electrons are
      the dominant origin of the chemical shifts in the Te I and Te II compounds and
      the chemical shifts were explained by the p-hole mechanism. The tellurium d
      electrons also play an important role in the chemical shifts of the hypervalent
      compounds.

PMID- 16095341
TI  - Response functions for dimers and square-symmetric molecules in four-wave-mixing
      experiments with polarized light.
AB  - Four-wave-mixing nonlinear-response functions are given for intermolecular and
      intramolecular vibrations of a perpendicular dimer and intramolecular vibrations
      of a square-symmetric molecule containing a doubly degenerate state. A two
      dimensional particle-in-a-box model is used to approximate the electronic wave
      functions and obtain harmonic potentials for nuclear motion. Vibronic
      interactions due to symmetry-lowering distortions along Jahn-Teller active normal
      modes are discussed. Electronic dephasing due to nuclear motion along both
      symmetric and asymmetric normal modes is included in these response functions,
      but population transfer between states is not. As an illustration, these response
      functions are used to predict the pump-probe polarization anisotropy in the limit
      of impulsive excitation.

PMID- 16095342
TI  - Nonperiodic boundary conditions for solvated systems.
AB  - The simulation of charged and/or strongly polar solutes represents a challenge
      for standard molecular-dynamics techniques. The use of periodic boundary
      conditions (PBCs) leads to artifacts due to the interaction between two replicas
      in the presence of the long-range Coulomb forces. A way to avoid these problems
      is the use of nonperiodic boundary conditions. A possible realization is to
      consider a finite system, a sphere, embedded in a reaction field described by the
      method of the images. In the present work the modified image approximation has
      been implemented in a molecular-dynamics code and optimized for the use of two
      standard solvents, water and acetonitrile. The methodology has then been applied
      to investigate the conformational changes in water-solvated alanine dipeptide.
      The free-energy surface calculated with this method is comparable to that
      obtained with PBC.

PMID- 16095343
TI  - Unprejudiced identification of reaction mechanisms from biased transition path
      sampling.
AB  - A method for unprejudiced investigation of reaction mechanisms from molecular
      dynamics simulations is presented. It combines the transition path sampling
      approach with a biasing strategy, which (a) allows optimization of transition
      paths crossing an energy minimum of the transition state surface. The bias is
      then used to (b) find reaction pathways, which follow different mechanistic
      routes. In the first step the manifold of similar trajectories that correspond to
      the same mechanism is reduced to a single characteristic dynamical path. Our
      method then allows a systematic search for further reaction mechanisms and the
      related energy barriers. It is illustrated at the example of a single particle in
      a two-dimensional potential and of the rather complex process of the pressure
      induced insertion of a helium atom into a C60 buckyball molecule.

PMID- 16095344
TI  - Density scaling and exchange-correlation energy.
AB  - The exchange-correlation energy is studied using the density scaling proposed by
      Chan and Handy [G. K.-L. Chan and N. C. Handy, Phys. Rev. A 59, 2670 (1999)]. It
      is shown that there exists a value of the scaling factor for which the
      correlation energy disappears. The optimized potential method and the Krieger-Li
      Iafrate approach are generalized to incorporate correlation.

PMID- 16095345
TI  - Higher-order response in O(N) by perturbed projection.
AB  - Perturbed projection for linear scaling solution of the coupled-perturbed self
      consistent-field equations [V. Weber, A.M.N. Niklasson, and M. Challacombe, Phys.
      Rev. Lett. 92, 193002 (2004)] is extended to the computation of higher-order
      static response properties. Although generally applicable, perturbed projection
      is further developed here in the context of the self-consistent first and second
      electric hyperpolarizabilities at the Hartree-Fock level of theory.
      Nonorthogonal, density-matrix analogs of Wigner's 2n+1 rule valid for linear one
      electron perturbations are given up to fourth order. Linear scaling and locality
      of the higher-order response densities under perturbation by a global electric
      field are demonstrated for three-dimensional water clusters.

PMID- 16095346
TI  - Nonorthogonal density-matrix perturbation theory.
AB  - Recursive density-matrix perturbation theory [A.M.N. Niklasson and M.
      Challacombe, Phys. Rev. Lett. 92, 193001 (2004)] provides an efficient framework
      for the linear scaling computation of materials response properties [V. Weber,
      A.M.N. Niklasson, and M. Challacombe, Phys. Rev. Lett. 92, 193002 (2004)]. In
      this article, we generalize the density-matrix perturbation theory to include
      properties computed with a perturbation-dependent nonorthogonal basis. Such
      properties include analytic derivatives of the energy with respect to nuclear
      displacement, as well as magnetic response computed with a field-dependent basis.
      The theory is developed in the context of linear scaling purification methods,
      which are briefly reviewed.

PMID- 16095347
TI  - Mutual information and correlation measures in atomic systems.
AB  - Mutual information is introduced as an electron correlation measure and examined
      for isoelectronic series and neutral atoms. We show that it possesses the
      required characteristics of a correlation measure and is superior to the behavior
      of the radial correlation coefficient in the neon series. A local mutual
      information, and related local quantities, are used to examine the local
      contributions to Fermi correlation, and to demonstrate and to interpret the
      intimate relationship between correlation and localization.

PMID- 16095349
TI  - A unified methodological framework for the simulation of nonisothermal ensembles.
AB  - A general framework is developed for the simulation of nonisothermal statistical
      mechanical ensembles. This framework is intended to synthesize the formulation of
      advanced Monte Carlo simulation methods such as multihistogram reweighting,
      replica-exchange methods, and expanded ensemble techniques so that they can be
      applied to different nonisothermal ensembles. Using Lennard-Jones systems as test
      cases, novel implementations of these methods are demonstrated with different
      ensembles including the microcanonical, isobaric-isoenthalpic, and isobaric
      semigrand ensembles. In particular, it is shown that the use of multiensemble
      methods allows the efficient simulation of microcanonical density of states,
      entropies, vapor-liquid and solid-liquid equilibrium for pure component systems,
      and fluid-phase coexistence for binary mixtures. In these applications,
      comparisons are also presented that highlight the advantages of the proposed
      multiensemble implementations over alternative methods used before.

PMID- 16095348
TI  - Intermolecular electrostatic energies using density fitting.
AB  - A method is presented to calculate the electron-electron and nuclear-electron
      intermolecular Coulomb interaction energy between two molecules by separately
      fitting the unperturbed molecular electron density of each monomer. This method
      is based on the variational Coulomb fitting method which relies on the expansion
      of the ab initio molecular electron density in site-centered auxiliary basis
      sets. By expanding the electron density of each monomer in this way the integral
      expressions for the intermolecular electrostatic calculations are simplified,
      lowering the operation count as well as the memory usage. Furthermore, this
      method allows the calculation of intermolecular Coulomb interactions with any
      level of theory from which a one-electron density matrix can be obtained. Our
      implementation is initially tested by calculating molecular properties with the
      density fitting method using three different auxiliary basis sets and comparing
      them to results obtained from ab initio calculations. These properties include
      dipoles for a series of molecules, as well as the molecular electrostatic
      potential and electric field for water. Subsequently, the intermolecular
      electrostatic energy is tested by calculating ten stationary points on the water
      dimer potential-energy surface. Results are presented for electron densities
      obtained at four different levels of theory using two different basis sets,
      fitted with three auxiliary basis sets. Additionally, a one-dimensional
      electrostatic energy surface scan is performed for four different systems (H2O
      dimer, Mg2+-H2O, Cu+-H2O, and n-methyl-formamide dimer). Our results show a very
      good agreement with ab initio calculations for all properties as well as
      interaction energies.

PMID- 16095350
TI  - Multielectron wave-packet propagation: general theory and application.
AB  - An ab initio method for multielectron wave-packet propagation in relatively large
      systems is presented. It allows the description of ultrafast electron dynamics
      processes before the coupling with the nuclear motion becomes important. The
      method is applied to the amino acid glycine for the investigation of the
      migration of hole charge following the ionization of the system. Two different
      mechanisms of ultrafast charge migration are identified and discussed. It is
      shown that the electron correlation can be the driving force for the charge
      transfer dynamics in glycine.

PMID- 16095351
TI  - Variational grand-canonical electronic structure method for open systems.
AB  - An ab initio method is developed for variational grand-canonical molecular
      electronic structure of open systems based on the Gibbs-Peierls-Boguliobov
      inequality. We describe the theory and a practical method for performing the
      calculations within standard quantum chemistry codes using Gaussian basis sets.
      The computational effort scales similarly to the ground-state Hartree-Fock
      method. The quality of the approximation is studied on a hydrogen molecule by
      comparing to the exact Gibbs free energy, computed using full configuration
      interaction calculations. We find the approximation quite accurate, with errors
      similar to those of the Hartree-Fock method for ground-state (zero-temperature)
      calculations. A further demonstration is given of the temperature effects on the
      bending potential curve for water. Some future directions and applications of the
      method are discussed. Several appendices give the mathematical and algorithmic
      details of the method.

PMID- 16095352
TI  - Vibrational dynamics of the floppy LiNC/LiCN molecular system.
AB  - Modern spectroscopical techniques allow the efficient experimental investigation
      of highly excited vibrational states in molecular systems. On the theoretical
      side, powerful computational methods have also been developed for the calculation
      of the corresponding energy levels and wave functions, and their interpretation.
      In this paper we use a combination of two such methods, namely, the distribution
      of zeroes in the Husimi function and energy-level correlation diagrams, to
      discuss a classification scheme, for the lowest hundred vibrational levels of the
      LiNC/LiCN floppy molecular system, based on their dynamical characteristics.

PMID- 16095353
TI  - An ab initio study of tunneling splittings in the water trimer.
AB  - Tunneling splittings in the water trimer have been determined by the
      semiclassical WKB method, based on pathways characterized at the computational
      level of second-order Moller-Plesset theory with basis sets of aug-cc-pVTZ
      quality. This calculation takes into account the single-flip and bifurcation
      tunneling rearrangements of the water trimer. The predicted splittings are 37.93
      cm(-1) for the flip and 6.50x10(-3) cm(-1) for bifurcation, which agree quite
      well with the corresponding experimental values of 43.52 cm(-1) and 9.63x10(-3)
      cm(-1).

PMID- 16095354
TI  - Density-functional study of two Fe4-based single-molecule magnets.
AB  - We present the results of our all-electron density-functional calculations on the
      electronic structure and magnetic anisotropy energy of the [Fe4(OMe)6(dpm)6] and
      [Fe4(thme)2(dpm)6] molecular clusters, which are experimentally found to behave
      as single-molecule magnets. The calculated magnetic anisotropy energy barriers
      are 2.65 and 15.8 K, respectively, which agree with the experimental data. We
      also present a density-functional study on the effect of the structure
      distortions on the magnetic anisotropy of the [Fe(H2O)6]3+ complex. This study,
      together with an analysis of the projected anisotropies of each iron ion in both
      molecular clusters, allows us to qualitatively understand why the magnetic
      anisotropy energy (MAE) barrier of the second single-molecule magnet (SMM) is
      larger than the MAE of the first SMM.

PMID- 16095355
TI  - The structure of 4-methylphenol and its water cluster revealed by rotationally
      resolved UV spectroscopy using a genetic algorithm approach.
AB  - The structure of 4-methylphenol (p-cresol) and its binary water cluster have been
      elucidated by rotationally resolved laser-induced fluorescence spectroscopy. The
      electronic origins of the monomer and the cluster are split into four sub-bands
      by the internal rotation of the methyl group and of the hydroxy group in case of
      the monomer, and the water moiety in case of the cluster. From the rotational
      constants of the monomer the structure in the S1 state could be determined to be
      distorted quinoidally. The structure of the p-cresol-water cluster is determined
      to be trans linear, with a O-O hydrogen bond length of 290 pm in the electronic
      ground state and of 285 pm in the electronically excited state. The S1-state
      lifetime of p-cresol, p-cresol-d1, and the binary water cluster have been
      determined to be 1.6, 9.7, and 3.8 ns, respectively.

PMID- 16095356
TI  - Electronic absorption spectra of linear and cyclic C(n)(+) n=7-9 in a neon
      matrix.
AB  - The C(n)(+) n=7-9 cations were produced by electron-impact ionization of
      perchloronaphthalene, mass selected, and their electronic absorption spectra in 6
      K neon matrices recorded. The linear and cyclic isomers of C7(+) and C8(+) are
      detected. Three systems of linear C7(+) are observed with origin bands near 770,
      332, and 309 nm. The cyclic C7(+) shows two transitions near 676 and 448 nm. One
      system of linear C9(+) is observed commencing at 371 nm. Linear C8(+) shows five
      dipole-allowed electronic transitions from the X 2pi(g) ground state, and the
      strongest ones have the origin bands at 890.8 and 308.1 nm. Five electronic
      transitions of cyclic C8(+) are also discernible.

PMID- 16095357
TI  - One-photon mass-analyzed threshold ionization spectroscopy of 2-chloropropene (2
      C3H5Cl) and its vibrational assignment based on the density-functional theory
      calculations.
AB  - A high-quality mass-analyzed threshold ionization (MATI) spectrum of 2
      chloropropene, 2-C3H5Cl, is reported. Its ionization energy determined for the
      first time from the 0-0 band position was 9.5395+/-0.0006 eV. Almost all the
      peaks in the MATI spectrum could be vibrationally assigned utilizing the
      frequencies calculated at the B3LYP6-311++G(3df,3pd) level and the Franck-Condon
      factors calculated with the molecular parameters obtained at the same level. In
      particular, the observed methyl torsional progression could be reproduced very
      well through quantum-mechanical calculations using the molecular parameters
      obtained at this level. Dramatic lowering of the torsional barrier inferred from
      the experimental data was entirely compatible with the B3LYP6-311++G(3df,3pd)
      results. The torsional barrier and the internal rotational constant determined by
      fits to six torsional peaks were 53.6 and 5.20 cm(-1), respectively. A brief
      discussion at the level of molecular orbital is presented to account for the
      dramatic lowering of the torsional barrier upon ionization.

PMID- 16095359
TI  - Hydrogen-bond interaction in 1:1 complexes of tetrahydrofuran with water,
      hydrogen fluoride, and ammonia: a theoretical study.
AB  - Ab initio and density-functional theory electronic structure calculations have
      been performed for the 1:1 complexes of tetrahydrofuran with water, hydrogen
      fluoride, and ammonia. Upon hydrogen bonding with H2O and HF, the structure of
      tetrahydrofuran (THF) remains relatively unchanged with the exception of THF
      sites involved in hydrogen-bonding interaction. But the similar findings are not
      true, upon hydrogen bonded with NH3, where the C2 symmetry of THF changed. The
      hydrogen-bonding strength for the 1:1 complexes of THF with water, HF, and NH3 is
      found to be in the order HF>H2O>NH3, which is well characterized by the order in
      bond angles O2H15F14, O2H16O14, and O2H15N14 closer to linearity, respectively,
      and the redshifted of stretching frequencies of upsilon(FH), upsilon(OH), and
      upsilon(NH), respectively. This work is an attempt to provide important
      predictions and to aid in future experimental and theoretical studies towards the
      understanding of such hydrogen-bonded van der Waals systems.

PMID- 16095358
TI  - Potential-energy surface and van der Waals motions of p-difluorobenzene-argon
      cation.
AB  - The structure and dynamics of the van der Waals complex of argon with the p
      difluorobenzene cation are investigated using the ab initio theory. The
      restricted open-shell Moller-Plesset second-order perturbation method combined
      with the augmented correlation-consistent polarized valence double-zeta basis set
      is employed to determine the electronic ground-state potential-energy surface of
      the cationic complex. This surface is extremely flat in a wide region of the
      configuration space of the Ar atom which moves almost freely over the monomer
      ring. However, it is bound to the monomer stronger in the cationic than in the
      neutral complex. Its binding energy is calculated to be 621 cm(-1) at a distance
      of 3.445 A from the monomer center. The calculated dissociation energy of 572 cm(
      1) agrees perfectly with the experimental value of 572+/-6 cm(-1) [S. M. Belm, R.
      J. Moulds, and D. Lawrence, J. Chem. Phys. 115, 10709 (2001)]. The effect of a
      strong coupling of large-amplitude intermolecular motions on the character of van
      der Waals vibrational states is investigated. The vibrational structure of the
      spectrum of the complex is explained and its earlier assignment is partly
      corrected.

PMID- 16095361
TI  - Thermal radiation from C(N)+ and La@C(N)+.
AB  - The radiative cooling of positively charged fullerene and endohedral fullerene
      fragments of C60, C70, C84, and La@C82 has been measured in a time-of-flight mass
      spectrometer. The radiative cooling is measured via its influence on the
      metastable decay. The emissivity extracted from the data is between 4x10(-4) and
      13x10(-4). These values agree fairly well with the emissivity calculated from
      considering the low-energy tail of the surface plasmon. No major difference is
      found in the emission behavior of empty and endohedral fullerenes.

PMID- 16095360
TI  - Vibrational energy transfer in O2(X 3sigma(g)-, upsilon=2,3) + O2 collisions at
      330 K.
AB  - Vibrational relaxation of O2(X 3sigma(g)-, upsilon=2,3) by O2 molecules is
      studied via a two-laser approach. Laser radiation at 266 nm photodissociates
      ozone in a mixture of molecular oxygen and ozone. The photolysis step produces
      vibrationally excited O2(a 1delta(g)) that is rapidly converted to O2(X 3sigma(g)
      , upsilon=2,3) in a near-resonant adiabatic electronic energy-transfer process
      involving collisions with ground-state O2. The output of a tunable 193-nm ArF
      laser monitors the temporal evolution of the O2(X 3sigma(g)-, upsilon=2,3)
      population via laser-induced fluorescence detected near 360 nm. The rate
      coefficients for the vibrational relaxation of O2(X 3sigma(g)-, upsilon=2,3) in
      collision with O2 are 2.0(-0.4)(+0.6) x 10(-13) cm3 s(-1) and (2.6+/-0.4) x 10(
      13) cm3 s(-1), respectively. These rate coefficients agree well with other
      experimental work but are significantly larger than those produced by various
      semiclassical theoretical calculations.

PMID- 16095362
TI  - Size-dependent properties of Zn(m)S(n) clusters: a density-functional tight
      binding study.
AB  - We present the results of our theoretical calculations on structural and
      electronic properties of ligand-free Zn(n)S(n) [with n ranging from 4 to 104 (0.8
      2.0-nm diameter)] clusters as a function of size of the clusters. We have
      optimized the structure whereby our initial structures are spherical parts of
      either zinc-blende or wurtzite structure. We have also considered some hollow
      bubblelike structures. The calculations are performed by using a parametrized
      linear combination of atomic orbitals-density-functional theory-local-density
      approximation-tight-binding method. We have focused on the variation of radial
      distribution function, Mulliken populations, electronic energy levels, band gap,
      and stability as a function of size for both zinc-blende and wurtzite-derived ZnS
      clusters. We have also reported the results of some nonstoichiometric Zn(m)S(n)
      (with m+n=47, 99, 177) clusters of zinc-blende modification.

PMID- 16095363
TI  - Equilibrium solvation in quadrupolar solvents.
AB  - We present a microscopic theory of equilibrium solvation in solvents with zero
      dipole moment and nonzero quadrupole moment (quadrupolar solvents). The theory is
      formulated in terms of autocorrelation functions of the quadrupolar polarization
      (structure factors). It can be therefore applied to an arbitrary dense
      quadrupolar solvent for which the structure factors are defined. We formulate a
      simple analytical perturbation treatment for the structure factors. The solute is
      described by coordinates, radii, and partial charges of constituent atoms. The
      theory is tested on Monte Carlo simulations of solvation in model quadrupolar
      solvents. It is also applied to the calculation of the activation barrier of
      electron transfer reactions in a cleft-shaped donor-bridge-acceptor complex
      dissolved in benzene with the structure factors of quadrupolar polarization
      obtained from molecular-dynamics simulations.

PMID- 16095364
TI  - Coherent and sequential contributions to femtosecond transient absorption spectra
      of a rhodamine dye in solution.
AB  - A unified description is presented of sequential and coherent contributions to
      optical transient absorption measured by femtosecond pump-supercontinuum probe
      spectroscopy. All inherent transient terms are taken into account. The "coherence
      spike" seen during pump-probe overlap is thereby decomposed into its components.
      The method is demonstrated with rhodamine 110 in methanol. Pure homogeneous
      dephasing times are obtained from a simultaneous fit of all pertinent
      measurements. Vibronic structure in the coherence spectrum is assigned to
      stimulated Raman scattering between vibrational levels in the first excited
      electronic state. The time-zero spectrum for stimulated emission and the
      solvation relaxation function are also obtained.

PMID- 16095365
TI  - The ferroelectric transition of dipolar hard spheres.
AB  - We investigate by Monte Carlo simulation the size dependence of the variation of
      the polarization and the dielectric constant with temperature for dipolar hard
      spheres at the two densities rho sigma3=0.80 and 0.88. From the crossing of the
      fourth-order cumulant for different system sizes first more precise estimates of
      the ferroelectric transition temperatures are obtained. Theoretical approaches,
      when predicting an ordering transition, are shown to generally overestimate the
      critical temperature.

PMID- 16095366
TI  - Laser control of vibrational excitation in carboxyhemoglobin: a quantum wave
      packet study.
AB  - A coherent control algorithm is applied to obtain complex-shaped infrared laser
      pulses for the selective vibrational excitation of carbon monoxide at the active
      site of carbonmonoxyhemoglobin, modeled by the six-coordinated iron-porphyrin
      imidazole-CO complex. The influence of the distal histidine is taken into account
      by an additional imidazole molecule. Density-functional theory is employed to
      calculate a multidimensional ground-state potential energy surface, and the
      vibrational dynamics as well as the laser interaction is described by quantum
      wave-packet calculations. At each instant in time, the optimal electric field is
      calculated and used for the subsequent quantum dynamics. The results presented
      show that the control scheme is applicable to complex systems and that it yields
      laser pulses with complex time-frequency structures, which, nevertheless, have a
      clear physical interpretation.

PMID- 16095367
TI  - Ab initio molecular-dynamics simulation of aqueous proton solvation and transport
      revisited.
AB  - The solvation and transport of the hydrated excess proton is studied using the
      Car-Parrinello molecular-dynamics (CPMD) simulation method. The simulations were
      performed using BLYP and HCTH gradient-corrected exchange-correlation energy
      functionals. The fictitious electronic mass was chosen to be small enough so that
      the underlying water structural and dynamical properties were converged with
      respect to this important CPMD simulation parameter. An unphysical
      overstructuring of liquid water in the CPMD simulations using the BLYP functional
      resulted in the formation of long-lived hydrogen-bonding structures involving the
      excess proton and a particular (special) water oxygen. The excess proton was
      observed to be attracted to the special oxygen through the entire length of the
      BLYP CPMD simulations. Consequently, the excess proton diffusion was limited by
      the mobility of the special oxygen in the slowly diffusing water network and, in
      turn, the excess proton self-diffusion coefficient was found to be significantly
      below the experimental value. On the other hand, the structural properties of
      liquid water in the HCTH CPMD simulation were seen to be in better agreement with
      experiment, although the water and excess proton diffusions were still well below
      the experimental value.

PMID- 16095368
TI  - Water liquid-vapor equilibria predicted by refined ab initio derived potentials.
AB  - Coexistence properties for water near the critical point using several ab initio
      models were calculated using grand canonical Monte Carlo simulations with
      multiple histogram reweighting techniques. These models, that have proved to
      yield a good reproduction of the water properties at ambient conditions, perform
      rather well, improving the performance of a previous ab initio model. It is also
      shown that bulk geometry and dipole values, predicted by the simulation, can be
      used and a good approximation obtained with a polarizable rigid water model but
      not when polarization is excluded.

PMID- 16095369
TI  - Molecular structure extracted from residual dipolar couplings: diphenylmethane
      dissolved in a nematic liquid crystal.
AB  - This paper describes an analysis of 1H-1H residual dipolar couplings (RDCs) in
      diphenylmethane (DPM) dissolved in a nematic liquid crystal, reported by Celebre
      et al. [J. Chem. Phys. 118, 6417 (2003)]. In that article, the conformational
      distribution function for DPM was extracted from the RDCs, using the additive
      potential (AP) model which is based on the molecular-field theory. The AP
      approach is a powerful, and frequently used, tool for analysis of the nuclear
      magnetic-resonance (NMR) parameters in liquid crystals. It requires, however, a
      priori knowledge of the functional form of the torsional potential, which may
      even for a simple molecule, such as DPM, be complicated to determine. Here, we
      analyze the same set of the RDCs using our APME procedure, which is a hybrid
      model based on the AP approach and maximum entropy (ME) theory. The APME
      procedure does not require any assumptions about the functional form of the
      torsional potential and, in contrast with the ME method, is applicable to weakly
      ordered systems. In the investigation reported in the present study, the results
      from the APME analysis are in good agreement with the AP interpretation, whereas
      the ME approach essentially fails in the extraction of the conformational
      distribution function for DPM.

PMID- 16095370
TI  - Luminescence spectroscopy of matrix-isolated atomic manganese: excitation of the
      "forbidden" a6D(J)<-->a6S transitions.
AB  - Laser-induced excitation spectra recorded for the electric-quadrupole 3d(6)4s
      a6D(J)<--3d(5)4s2a6S(5/2) transitions of atomic Mn, allow assignment of the red
      emission features, previously observed in Mn/RG (RG=Ar, Kr and Xe) matrices with
      resonance 3d(5)4s4pz6P(5/2)<--3d(5)4s2 a6S(5/2) excitation, to the metastable
      a6D(9/2) state. Narrow excitation bands recorded for the red site in the Mn/Kr
      system allow identification of all five spin-orbit levels (J=1/2, 3/2, 5/2, 7/2
      and 9/2) in the a6D state. The coincidence of the lowest energy excitation band
      and the observed 585.75 nm (17,072 cm(-1)) emission band of atomic Mn in Kr
      matrices, yielded a definitive assignment of this emission to a transition from
      the J=9/2 spin-orbit level. Temperature dependent emission scans lead to the
      identification of the zero phonon line for the a6D(9/2)-->a6S(5/2) transition at
      585.75 nm. The identified matrix-shift of +20 cm(-1) allows an assessment of the
      extent of the ground state stabilization in the red (secondary) site of atomic Mn
      isolation in solid Kr. Emission produced with direct a6D state excitation yielded
      both the 585.75 and 626 nm features. The former band arises for Mn atoms
      occupying the red site--the latter from blue site occupancy in solid Kr. The
      excitation linewidths recorded for these two sites differ greatly, with the blue
      site yielding a broad featureless profile, in contrast to the narrow, structured
      features of the red site. The corresponding red site a6D(J)<-->a6S(5/2)
      transitions in Ar and Xe matrices are broader than in Kr--a difference considered
      to originate from the site sizes available in these hosts and the interatomic Mn
      x RG potentials. The millisecond decay times recorded for the red emission bands
      in the Mn/RG systems are all much shorter than the 3 s value predicted for the
      gas phase a6D(9/2)-->a6S(5/2) transition. This enhancement allows optical pumping
      of the forbidden a6D(J)<-->a6S transitions with low laser powers when atomic
      manganese is isolated in the solid state. However all the emission decays are
      complex, exhibiting triple exponential decays. This behavior may be related to
      the dependence of the excitation linewidths on the J value, indicating removal of
      the J degeneracy due to weak matrix-induced, crystal field splitting.

PMID- 16095371
TI  - A comparison of fine structures in high-resolution x-ray-absorption spectra of
      various condensed organic molecules.
AB  - We report on a high-resolution C-K and O-K near-edge x-ray-absorption fine
      structure (NEXAFS) study of large aromatic molecules in condensed thin films,
      namely, anhydrides 1,4,5,8-naphthalene-tetracarboxylic acid dianhydride, 3,4,9,10
      perylene-tetracarboxylic acid dianhydride, benzoperylene-(1,2)-dicarboxylic acid
      anhydride, and 1,8-naphthalene-dicarboxylic acid anhydride and the quinoic
      acenaphthenequinone. Due to the high-energy resolution of the third-generation
      synchrotron source BESSY II we observe large differences in the NEXAFS fine
      structures even for very similar molecules, resulting in a wealth of new
      information. The rich fine structure can unambiguously be assigned to the
      coupling of electronic transitions to vibronic excitations. Backed by ab initio
      calculations we present a detailed analysis of the spectra that allows the
      complete interpretation of the near-edge features. It also yields information on
      the vibronic properties in the electronically excited state as well as on the
      response of the electronic system upon core excitation. The strong differences in
      the electron-vibron coupling for different molecules are discussed.

PMID- 16095372
TI  - Are defect models consistent with the entropy and specific heat of glass formers?
AB  - We show that pointlike defect model of glasses cannot explain the thermodynamic
      properties of glass formers, as for example, the excess specific heat close to
      the glass transition, contrary to the claim of Garrahan and Chandler [Proc. Natl.
      Acad. Sci. U.S.A. 100, 9710 (2003)]. More general models and approaches in terms
      of extended defects are also discussed.

PMID- 16095373
TI  - Thermodynamics of coarse-grained models of supercooled liquids.
AB  - In recent papers, we have argued that kinetically constrained coarse-grained
      models can be applied to understand dynamic properties of glass-forming
      materials, and we have used this approach in various applications that appear to
      validate this view. In one such paper [J. P. Garrahan and D. Chandler, Proc.
      Natl. Acad. Sci. U.S.A. 100, 9710 (2003)], among other things we argued that this
      approach also explains why the heat-capacity discontinuity at the glass
      transition is generally larger for fragile materials than for strong materials.
      In the preceding article, Biroli, Bouchaud, and Tarjus have objected to our
      explanation on this point, arguing that the class of models we apply is
      inconsistent with both the absolute size and the temperature dependence of the
      experimental specific heat. Their argument, however, neglects parameters
      associated with the coarse graining. Accounting for these parameters, we show
      here that our treatment of dynamics is not inconsistent with heat-capacity
      discontinuities.

PMID- 16095374
TI  - Chemical potentials and phase equilibria of Lennard-Jones mixtures: a self
      consistent integral equation approach.
AB  - We explore the vapor-liquid phase behavior of binary mixtures of Lennard-Jones
      type molecules where one component is supercritical, given the system
      temperature. We apply the self-consistency approach to the Ornstein-Zernike
      integral equations to obtain the correlation functions. The consistency checks
      include not only thermodynamic consistencies (pressure consistency and Gibbs
      Duhem consistency), but also pointwise consistencies, such as the zero-separation
      theorems on the cavity functions. The consistencies are enforced via the bridge
      functions in the closure which contain adjustable parameters. The full solution
      requires the values of not only the monomer chemical potentials, but also the
      dimer chemical potentials present in the zero-separation theorems. These are
      evaluated by the direct chemical-potential formula [L. L. Lee, J. Chem. Phys. 97,
      8606 (1992)] that does not require temperature nor density integration. In order
      to assess the integral equation accuracy, molecular-dynamics simulations are
      carried out alongside the states studied. The integral equation results compare
      well with simulation data. In phase calculations, it is important to have
      pressure consistency and valid chemical potentials, since the matching of phase
      boundaries requires the equality of the pressures and chemical potentials of both
      the liquid and vapor phases. The mixtures studied are methane-type and pentane
      type molecules, both characterized by effective Lennard-Jones potentials.
      Calculations on one isotherm show that the integral equation approach yields
      valid answers as compared with the experimental data of Sage and Lacey. To study
      vapor-liquid phase behavior, it is necessary to use consistent theories; any
      inconsistencies, especially in pressure, will vitiate the phase boundary
      calculations.

PMID- 16095375
TI  - Pronounced non-Condon effects in the ultrafast infrared spectroscopy of water.
AB  - In the context of vibrational spectroscopy in liquids, non-Condon effects refer
      to the dependence of the vibrational transition dipole moment of a particular
      molecule on the rotational and translational coordinates of all the molecules in
      the liquid. For strongly hydrogen-bonded systems, such as liquid water, non
      Condon effects are large. That is, the bond dipole derivative of an OH stretch
      depends strongly on its hydrogen-bonding environment. Previous calculations of
      nonlinear vibrational spectroscopy in liquids have not included these non-Condon
      effects. We find that for water, inclusion of these effects is important for an
      accurate calculation of, for example, homodyned and heterodyned three-pulse
      echoes. Such echo experiments have been "inverted" to obtain the OH stretch
      frequency time-correlation function, but by necessity the Condon and other
      approximations are made in this inversion procedure. Our conclusion is that for
      water, primarily because of strong non-Condon effects, this inversion may not
      lead to the correct frequency time-correlation function. Nevertheless, one can
      still make comparison between theory and experiment by calculating the
      experimental echo observables themselves.

PMID- 16095376
TI  - Cooperativity of dynamics of 18-crown-6 molecule forming one-dimensional chain in
      Cs2(18-crown-6)3[Ni(dmit)2]2.
AB  - Heat capacity of Cs2(18-crown-6)3[Ni(dmit)2]2 was measured by adiabatic
      calorimetry. A broad thermal anomaly was observed around 225 K. The entropy gain
      (about 52 J K(-1) mol(-1)) is much larger than that expected for twofold
      disordering of 18-crown-6 assumed in the previous structure analysis. The shape
      of thermal anomaly was qualitatively explained by a linear Ising model developed
      for cooperative disordering in polymers. The 18-crown-6 molecules forming a one
      dimensional chain in the crystal are orientationally disordered with moderate
      cooperativity.

PMID- 16095377
TI  - Liquid-liquid phase transitions in supercooled water studied by computer
      simulations of various water models.
AB  - Liquid-liquid and liquid-vapor coexistence regions of various water models were
      determined by Monte Carlo (MC) simulations of isotherms of density fluctuation
      restricted systems and by Gibbs ensemble MC simulations. All studied water models
      show multiple liquid-liquid phase transitions in the supercooled region: we
      observe two transitions of the TIP4P, TIP5P, and SPCE models and three
      transitions of the ST2 model. The location of these phase transitions with
      respect to the liquid-vapor coexistence curve and the glass temperature is highly
      sensitive to the water model and its implementation. We suggest that the apparent
      thermodynamic singularity of real liquid water in the supercooled region at about
      228 K is caused by an approach to the spinodal of the first (lowest density)
      liquid-liquid phase transition. The well-known density maximum of liquid water at
      277 K is related to the second liquid-liquid phase transition, which is located
      at positive pressures with a critical point close to the maximum. A possible
      order parameter and the universality class of liquid-liquid phase transitions in
      one-component fluids are discussed.

PMID- 16095378
TI  - Photoluminescence of oxygen-containing surface defects in germanium oxides: a
      theoretical study.
AB  - Photoabsorption and photoluminescence properties of nonbridging oxygen -O
      Ge[triple bond](NBO), -OO-Ge[triple bond] (peroxy radical), O=Ge=, and (O2)Ge=
      defects in germanium oxides have been investigated by high-level ab initio
      calculations. Geometry optimization for excited electronic states of model
      clusters simulating these defects was carried out at the complete-active-space
      self-consistent-field level, and relative energies were calculated by various
      methods including time-dependent density-functional theory, outer-valence Green's
      functions, equation-of-motion coupled cluster theory with single and double
      excitations, symmetry-adapted cluster configuration interaction, multireference
      second-order perturbation theory, and multireference configuration interaction.
      The results demonstrate that the considered excited states of the aforementioned
      defects normally exhibit large Stokes shifts and that, with few exceptions, UV
      photoabsorption is accompanied by red or IR photoluminescence.

PMID- 16095380
TI  - Coulomb blockade of small Pd clusters.
AB  - Single-electron tunneling through Au substrate-alkanethiol-Pd cluster-tip
      junctions is investigated with scanning tunneling spectroscopy. The measured I(V)
      curves reveal several characteristic features of the Coulomb blockade, namely,
      the presence of a Coulomb gap and a Coulomb staircase. By using the orthodox
      theory of single-electron tunneling, the capacitances and resistances of the
      double junction system as well as the fractional charge are extracted from the
      experimental data.

PMID- 16095379
TI  - Characterization of the restricted rotation of the dimethyl groups in chemically
      N-terminal 13C-labeled antifreeze glycoproteins: a temperature-dependent study in
      water to ice through the supercooled state.
AB  - Site-specific chemical modification, especially with isotopically enriched
      groups, allows one to study the structure and dynamics of proteins for which
      uniform enrichment is difficult. When the N-terminal alanine in antifreeze
      glycoprotein (AFGP) is replaced with an N,N-dimethyl alanine the methyl groups
      show signatures of slow rotation about the C-N bond. In order to separate the
      local dynamics of the N-terminus from the overall protein dynamics, we present a
      complete characterization of this dynamics. Temperature-dependent nuclear
      magnetic-resonance experiments from room temperature to subzero temperatures,
      including the supercooled state and in the presence of ice, are presented.
      Quantum chemical calculations are also performed on a localized N-terminus of the
      AFGP. Our results show that in the solution state at room temperature and in the
      super cooled regime, the dimethyl groups undergo a slow, restricted rotation with
      an unequal distribution of population between two major conformations. At lower
      temperatures in the presence of ice, the dynamics become much more complex due to
      freezing out of several conformational states. Based on these results, we
      conclude that the segmental dynamics of the N-terminus are local to the first
      residue and do not affect the overall dynamics of the protein.

PMID- 16095381
TI  - Electrochemical and optical characterization of p- and n-doped poly[2-methoxy-5
      (2-ethylhexyloxy)-1,4-phenylenevinylene].
AB  - We study electrochemical p- and n-type doping in the well-known light-emitting
      polymer poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV).
      Doping reactions are characterized using cyclic voltammetry. Optical measurements
      including photoluminescence and UV/Vis/NIR transmission were performed on doped
      samples. We find that oxidation in MEH-PPV is a highly reversible reaction
      resulting in stable freestanding doped films, while the reduced form is unstable
      and the reaction irreversible. We discuss the dependence of doping reactions on
      scan rate, film thickness, salt type and concentration, and working electrode
      type. We observe the development of two additional broad absorption bands in both
      lightly and heavily doped films accompanied by a slight blueshift in the primary
      optical transition, suggesting bipolaron band formation. Finally we find that
      both p and n dopings result in extremely sensitive photoluminescence quenching.
      We propose a physical model for understanding electrochemical doping in MEH-PPV
      and the implications this has on the development of such technologies as polymer
      light-emitting electrochemical cells, electrochromic devices, actuators, and
      sensors.

PMID- 16095382
TI  - Air separation by single wall carbon nanotubes: thermodynamics and adsorptive
      selectivity.
AB  - Separation of a nitrogen-oxygen mixture (air) by single wall carbon nanotubes has
      been studied using grand canonical Monte Carlo simulations at a range of nanotube
      diameters, temperatures, and pressures. It is demonstrated that depending on
      these operating parameters, the extent of adsorptive selectivity can vary
      significantly. Detailed calculations are also presented for the adsorption
      isotherms, energies, and isosteric heats of pure nitrogen, oxygen, and their
      mixture at 100 K in a carbon nanotube of 12.53-A diameter. In single-component
      simulations, it is found that near saturation loading nitrogen forms only an
      annular layer close to the nanotube wall, while smaller-sized oxygen also
      occupies the region near the center of the nanotube. In mixture adsorption, the
      energetically favored nitrogen is preferentially adsorbed at low loadings.
      However, at high loadings oxygen replaces nitrogen due to the dominant entropic
      effects, and therefore a high selectivity towards oxygen is observed close to the
      saturation loading. The effect of the entropic change on mixture adsorption is
      evident from the calculated isosteric heats of adsorption. The mixture isotherms
      obtained from simulations are found to be in good agreement with the predictions
      based only on the pure component simulation results.

PMID- 16095383
TI  - Noncontact atomic force microscopy studies of ultrathin films of amorphous solid
      water deposited on Au(111).
AB  - Noncontact atomic force microscopy was used to study the morphological changes of
      an ultrathin amorphous solid water (ASW) film as a function of deposition
      temperature, annealing temperature, and annealing time. ASW deposited at 80 or
      108 K on Au(111) formed truncated hemispherical clusters of increasing size
      during annealing at 134 K; these clusters were inferred to be crystalline. The
      number of nuclei present at the outer surface of the film after deposition was
      greater for higher deposition temperature. For lower cluster densities, depletion
      of the ASW film around the clusters was observed when the clusters became larger
      and dendritic growth was observed when the apparent cluster footprint radius
      exceeded 100 nm.

PMID- 16095384
TI  - SERS in PAH-Os and gold nanoparticle self-assembled multilayers.
AB  - We present a detailed structural and surface-enhanced Raman scattering (SERS)
      study of poly(allylamine) modified with Os(byp)2ClPyCHO (PAH-Os) and gold
      nanoparticles self-assembled multilayers [PAH-Os+(Au-nanoparticlesPAH-Os)n, n=1
      and 5]. Atomic force microscopy and variable-angle spectroscopic ellipsometry
      measurements indicate that the first nanoparticle layer grows homogenously by
      partially covering the substrate without clustering. Analyzing the sample
      thickness and roughness we infer that the growth process advances thereafter by
      filling with nanoparticles the interstitial spaces between the previously
      adsorbed nanoparticles. After five immersion steps the multilayers reach a more
      compact structure. The interaction between plasmons of near-gold nanoparticles
      provides a new optical absorption around 650 nm which, in addition, allows a more
      effective SERS process in that spectral region than at the single-plasmon
      resonance (approximately 530 nm). We compare the electronic resonance Raman and
      SERS amplification mechanisms in these self-assembled multilayers analyzing Raman
      resonance scans and Raman intensity micromaps. As a function of nanoparticle
      coverage we observe large changes in the Raman intensity scans, with maxima that
      shift from the electronic transitions, to the plasmon resonance, and finally to
      the coupled-plasmon absorption. The Raman micromaps, on the other hand, evidence
      huge intensity inhomogeneities which we relate to "hot spots." Numerical discrete
      dipole approximation calculations including the interaction between gold
      nanoparticles are presented, providing a qualitative model for the coupled
      plasmon absorption and redshifted Raman hot spots in these samples.

PMID- 16095385
TI  - Monte Carlo simulations of hydrogen adsorption in alkali-doped single-walled
      carbon nanotubes.
AB  - Monte Carlo simulations and Widom's test particle insertion method have been used
      to calculate the solubility coefficients (S) and the adsorption equilibrium
      constants (K) in single-walled (10,10) armchair carbon nanotubes including single
      nanotubes, and nanotube bundles with various configurations with and without
      alkali dopants. The hydrogen adsorption isotherms at room temperature were
      predicted by following the Langmuir adsorption model using the calculated
      constants S and K. The simulation results were in good agreement with
      experimental data as well as the grand canonical Monte Carlo simulation results
      reported in the literature. The simulations of nanotube bundle configurations
      suggest that the gravimetric hydrogen adsorption increases with internanotube gap
      size. It may be attributed to favorable hydrogen-nanotube interactions outside
      the nanotubes. The effect of alkali doping on hydrogen adsorption was studied by
      incorporating K+ or Li+ ions into nanotube arrays using a Monte Carlo simulation.
      The results on hydrogen adsorption isotherms indicate hydrogen adsorption of 3.95
      wt% for K-doping, and 4.21 wt% for Li-doping, in reasonable agreement with the
      experimental results obtained at 100 atm and room temperature.

PMID- 16095386
TI  - Orientational order and finite strain in nematic elastomers.
AB  - Nematic elastomers exhibit large, spontaneous shape changes at the transition
      from the high-temperature isotropic phase to the low-temperature nematic phase.
      These finite deformations are studied here in the context of a nonlinear,
      properly invariant, variational theory that couples the orientational order and
      elastic deformation. The theory is based on the minimization of a free-energy
      functional that consists of two contributions: a nematic one due to the
      interaction of the mesogenic units and an elastic one arising from the stretching
      of the cross-linked polymer chains. Suitable choices for these two contributions
      allow for large, reversible, spontaneous shape changes in which the elastic
      deformation can affect the isotropic-nematic transition temperature. The change
      in transition temperature as well as the magnitude of the resulting spontaneous
      deformation is illustrated for various parameter values. The theory includes soft
      elasticity as a special case but is not restricted to it.

PMID- 16095387
TI  - Backtracking of a sphere slowing down in a viscous compressible fluid.
AB  - It is shown on the basis of the linearized Navier-Stokes equations that a sphere
      set in motion by a sudden impulse, and slowing down in a viscous compressible
      fluid, can temporarily reverse its velocity at a late stage of the motion before
      finally slowing down with a positive velocity. For the effect to occur, the fluid
      needs to be sufficiently compressible, and the bulk viscosity needs to be
      sufficiently small relative to the shear viscosity. More generally, the velocity
      decays nonmonotonically, without necessarily passing through zero. The results
      are derived from the frequency-dependent friction coefficient, and hold for
      general boundary condition on the surface of the sphere.

PMID- 16095388
TI  - Comment on "Theoretical study of the photoinduced transfer among the ground state
      and two metastable states in [Fe(CN)5NO]2-" [J. Chem. Phys. 122, 074314 (2005)].
AB  - We discuss the computational results of the "Theoretical study of the
      photoinduced transfer among the ground state and two metastable states in
      [Fe(CN)5NO]2-" [J. Chem. Phys. 122, 074314 (2005)] with respect to our previously
      reported polarized absorption study on the metastable states SI and SII in
      Na2[Fe(CN)5NO]2H2O [D. Schaniel, J. Schefer, B. Delley, M. Imlau, and Th. Woike,
      Phys. Rev. B 66, 085103 (2002)].

PMID- 16095394
TI  - Body size and composition of National Football League players.
AB  - The purpose of this study was to present a profile of body size and composition
      of National Football League (NFL) players prior to the start of the regular
      season. Fifty-three members of the Indianapolis Colts professional football team
      were measured for height, body mass, and percentage body fat using the BOD POD
      air-displacement plethysmography system during summer camp of the 2003 football
      season. These data were categorized by position for comparison with previous
      studies of NFL football players. The relationships observed were as follows (=
      represents nonsignificant; > represents p < or = 0.05): Height: Offensive Line =
      Defensive Line = Quarterbacks/Kickers/Punters = Tight Ends > Linebackers >
      Running Backs = Wide Receivers = Defensive Backs. Body Mass: Offensive Line =
      Defensive Line > Tight Ends = Linebackers > Running Backs = Quarterbacks/
      Kickers/Punters > Wide Receivers = Defensive Backs. Percentage Body Fat:
      Offensive Line > Defensive Line > Quarterbacks/ Kickers/Punters = Linebackers =
      Tight Ends > Running Backs = Wide Receivers = Defensive Backs. Comparisons to
      teams in the 1970s indicate that body mass has increased only for offensive and
      defensive linemen; however, height and body fat among player positions have not
      dramatically changed. Furthermore, the body mass index is not an accurate measure
      or representation of body fat or obesity in NFL players. These data provide a
      basic template for size profiles and differences among various positions and
      allow comparisons with other studies for changes in the NFL over the past 3
      decades.

PMID- 16095395
TI  - Evaluation of dietary practices of National Collegiate Athletic Association
      Division I football players.
AB  - The objective of this study is to evaluate the dietary practices of 28 football
      athletes on a National Collegiate Athletic Association (NCAA) Division I team
      using 3-day diet records. Student athletes completed 3-day diet records at 2
      individual points of time, when no training table was available. Diet records
      were evaluated and were compared with the Third National Health and Nutrition
      Survey (NHANES III) data for the same ages and gender group. No differences in
      dietary practices of collegiate football athletes were observed when compared
      with data for the same ages and gender group culled from NHANES III. Inadequacies
      in energy intake for activity level were significant (p < 0.05). Influences of
      fad dieting trends were noted when the diets were mapped onto the United States
      Department of Agriculture (USDA) food guide pyramid. Changes in diet would be
      necessary to sustain the activity level of these athletes.

PMID- 16095396
TI  - Strength and conditioning practices of National Basketball Association strength
      and conditioning coaches.
AB  - This study describes the results of a survey of the practices of National
      Basketball Association strength and conditioning (NBA S&C) coaches. The response
      rate was 68.9% (20 of 29). This survey examines (a) background information, (b)
      physical testing, (c) flexibility development, (d) speed development, (e)
      plyometrics, (f) strength/power development, (g) unique aspects, and (h) comments
      from coaches providing additional information. Results indicate, in part, that
      coaches assess an average of 7.3 parameters of fitness, with body composition
      testing being the most common. All coaches used a variety of flexibility
      development strategies. Results reveal that 17 of 20 (85.0%) of NBA S&C coaches
      follow a periodization model. Nineteen of 20 coaches (95.0%) indicated that their
      athletes used Olympic-style lifts. All coaches employed plyometric exercises with
      their athletes. The squat and its variations, as well as the Olympic-style lifts
      and their variations, were the most frequently used exercises. The survey serves
      as a review and a source of applied information and new ideas.

PMID- 16095397
TI  - Effects of a competitive wrestling season on body composition, strength, and
      power in National Collegiate Athletic Association Division III college wrestlers.
AB  - The purpose of this study was to investigate the effects of a competitive
      wrestling season on body composition, muscular strength, and muscular power in
      National Collegiate Athletic Association (NCAA) Division III college wrestlers. A
      total of 10 wrestlers were assessed throughout 2 consecutive wrestling seasons in
      late October, late January (midseason), and late March (postseason). Measurements
      included body weight, body composition (6-site skinfold), muscular strength (back
      squats and bench press), and muscular power (e.g., power cleans, vertical jump,
      seated medicine ball put). A repeated-measures analysis of variance (ANOVA)
      showed no significant changes in body weight, percentage of body fat, or fat-free
      mass (FFM) from pre- to mid- to postseason (body weight, 77.9 +/- 12.4, 75.7 +/-
      11.0, and 79.9 +/- 12.8 kg; percentage of body fat, 11.6 +/- 3.9, 10.5 +/- 3.0,
      and 12.0 +/- 3.4; FFM, 68.5 +/- 8.7, 67.5 +/- 8.2, and 70.0 +/- 9.0 kg). A
      statistically significant main effect of time (p < 0.01) was observed for
      muscular strength, as both the back squat and bench press measures were lower at
      midseason (back squat, 150.8 +/- 25.2 kg; bench press, 98.3 +/- 25.4 kg) than at
      pre- and postseason (back squat, 157.9 +/- 25.5 and 161.4 +/- 25.6; bench press,
      103.4 +/- 25.5 and 106.4 +/- 26.0). Muscular power did not change significantly
      throughout the wrestling season. These data indicate that Division III college
      wrestlers remain relatively weight stable with little change in body composition
      during a competitive wrestling season. While muscular power is apparently
      maintained, muscular strength may decline slightly. Our findings suggest that
      these wrestlers benefit from a training program that emphasizes in-season
      strength maintenance.

PMID- 16095398
TI  - The effect of a competitive collegiate football season on power performance and
      muscle oxygen recovery kinetics.
AB  - Ten intercollegiate football players were tested within 3 days prior to (T1) and
      the day following the end (T2) of football preseason training camp and during
      weeks 7 (T3) and 11 (T4) of the competitive season. During each testing session,
      subjects performed a 30-second Wingate anaerobic power test. Near-infrared
      continuous wave spectroscopy was used to measure muscle deoxygenation during
      exercise. No changes in any power performance measures were seen during the
      competitive football season. A significant (p < 0.05) decrease in the extent of
      deoxygenation during exercise was observed between T2 (72.6 +/- 19.4%) and T4
      (50.2 +/- 14.2%). A 30 and 29% difference (p < 0.05) in the onset of
      reoxygenation was observed between T1 and T3 and T4, respectively. A 51% decrease
      (p < 0.05) in halftime recovery was observed between T2 and T3. Results indicate
      that the extent of muscle deoxygenation is reduced during high-intensity exercise
      and that muscle oxygen recovery kinetics improves over the duration of a
      competitive season of football.

PMID- 16095399
TI  - Comparison of the backward overhead medicine ball throw to power production in
      college football players.
AB  - The purpose of this study was to determine the relationship of the backward
      overhead medicine ball (BOMB) throw to power production in college football
      players. Forty National Collegiate Athletic Association Division II college
      football players were studied at the end of an 8-week off-season conditioning
      program for power output determined from a countermovement vertical jump on a
      force plate and for maximal distance in the standing BOMB throw. Although the
      reliability of the BOMB test was high (interclass correlation coefficient =
      0.86), there was a significant learning effect across 3 trials (p < 0.01). Peak
      and average powers generated during the vertical jump correlated moderately but
      significantly with the best BOMB throw distance (r = 0.59 and 0.63,
      respectively). Considering power relative to body mass or lean body mass failed
      to produce significant correlations with BOMB throw distance (r = 0.27 and 0.28,
      respectively). Therefore, the BOMB throw may have limited potential as a
      predictor of total body explosive power in college football players.

PMID- 16095400
TI  - Correlation analyses and regression modeling between isokinetic testing and on
      court performance in competitive adolescent tennis players.
AB  - Tennis requires skill, physical attributes, and strategy. Ball velocity and
      placement are two of the most important components in winning the faster-paced
      modern game. Although isokinetic testing has been used to evaluate physical
      characteristics and injury potential in tennis players, few studies have compared
      isokinetics and on-court performance. Such a comparison would help establish
      links between speed-specific properties of functioning muscles and stroke
      production and could affect overall training strategy. This study compared
      isokinetic peak torque (PT), average power (AP), and total work (TW) during
      specific testing patterns correlated with ball velocity or stroke accuracy during
      the service, forehand, and backhand and developed predictive equations for each
      stroke using these variables. Thirty-five players, aged 13-18 years with at least
      4 years playing experience, were evaluated using internal and external shoulder
      rotation, leg extension, and diagonal throwing motions. Ball velocity was
      measured using a radar gun. Accuracy was evaluated on the basis of shot position
      and depth. Significant correlations were found between ball velocity and a number
      of isokinetic variables, while no significant correlations were observed with
      shot accuracy. Significant isokinetic variables for each stroke were entered into
      regression models. One isokinetic speed sufficiently predicted ball velocity for
      each stroke, since no increase in predictive capacity was observed with the
      addition of other isokinetic parameters. We conclude that isokinetics at testing
      speeds between 1.57 and 4.71 rad.s(-1) can effectively predict ball velocity, but
      not accuracy, and that our results may be helpful in planning strategies for
      training and rehabilitation.

PMID- 16095401
TI  - Strength and conditioning practices of Major League Baseball strength and
      conditioning coaches.
AB  - This study describes the results of a survey of the practices of Major League
      Baseball strength and conditioning (MLB S&C) coaches. The response rate was 70.0%
      (21 of 30). This survey examines (a) background information, (b) physical
      testing, (c) flexibility development, (d) speed development, (e) plyometrics, (f)
      strength/power development, (g) unique aspects, and (h) comments. Results
      indicate, in part, that coaches assess an average of 3.6 parameters of fitness,
      with body composition testing being the most commonly assessed parameter. All
      coaches use a variety of flexibility development strategies. All coaches use
      speed development strategies, with form running drills being the most common.
      Twenty of 21 (95.2%) coaches employ plyometric exercises with their athletes.
      Eighteen of 21 (85.7%) of MLB S&C coaches follow a periodization model (PM). Five
      of 21 coaches (23.8%) indicated that their athletes use Olympic-style lifts. The
      squat and its variations and the lunge and its variations were most frequently
      identified as the first and second most important exercises used to train the
      athletes. This survey provides detailed information about strength and
      conditioning practices at the most competitive level of baseball and serves as a
      review, as well as a source of applied information and new ideas.

PMID- 16095402
TI  - Development and validation of a core endurance intervention program: implications
      for performance in college-age rowers.
AB  - The objective of this study was to examine the effectiveness of a core endurance
      exercise protocol. Forty-five college-age rowers (age 21 +/- 1.0) were assigned
      to either a core training group [core group] (n = 25), which took part in a core
      endurance intervention exercise protocol, or to a control training group [control
      group] (n = 20), which was not given any specialized core training. Training took
      place 2 days per week for 8 weeks. Trunk endurance was assessed using flexion,
      extension, and side flexion tests, whereas a variety of functional performance
      measures were assessed (vertical jump, broad jump, shuttle run, 40-m sprint,
      overhead medicine ball throw, 2,000-m maximal rowing ergometer test). The results
      revealed significant improvement in the two side flexion tests for the core group
      (p < 0.05). Interestingly, significant differences were noted in the trunk
      extension test endurance times for the control group (p < 0.05), but not for the
      core group. No significant differences were found for any of the functional
      performance tests. In summary, the 8-week core endurance training program
      improved selected core endurance parameters in healthy young men, but the
      effectiveness of the core intervention on various functional performance aspects
      was not supported.

PMID- 16095403
TI  - A comparison of methods for estimating the lactate threshold.
AB  - The purpose of this study was to examine the accuracy of tests that may be used
      by distance runners to estimate the lactate threshold. Competitive distance
      runners/triathletes (N = 27) performed a criterion test that directly measured
      (blood lactate of 4.0 mmol.L(-1)) the lactate threshold. Subjects then performed
      4 tests (VDOT, 3,200-m time trial, 30-minute time trial, Conconi) that estimate
      the threshold. Mean estimations of the running velocity at the lactate threshold
      from the 30-minute time trial (standard error of the estimate, SEE, 0.21 m.s(-1))
      and VDOT (SEE 0.41 m.s(-1)) methods did not differ (P>0.05) from the criterion.
      In terms of heart rate, the 30-minute time trial estimation did not significantly
      differ (SEE 8.0 b.min(-1)) from criterion. These findings suggest that the 30
      minute time-trial method should be considered by coaches and distance
      runners/triathletes as a method for estimating both the running velocity and
      heart rate at the lactate threshold.

PMID- 16095404
TI  - Acute hormonal responses to submaximal and maximal heavy resistance and explosive
      exercises in men and women.
AB  - The purpose of this study was to examine acute hormonal and neuromuscular
      responses in men and women to 3 heavy resistance but clearly different exercise
      protocols: (a) submaximal heavy resistance exercise (SME), (b) maximal heavy
      resistance exercise (HRE), and (c) maximal explosive resistance exercise (EE).
      HRE included 5 sets of 10 repetition maximum (10RM) sit-ups, bench press, and
      bilateral leg extensions (David 210 machine) with a 2-minute recovery between the
      sets. In SME, the load was 70%, and in EE, the load was 40% from that used in
      HRE. A significant increase (p < 0.05) in serum growth hormone (GH) was observed
      after HRE both in men and women, but the increase was greater (p < 0.05) in men
      than in women. Serum testosterone (T) increased significantly (p < 0.05) only
      during HRE in men. Since GH and T are anabolic hormones, the acute exercise
      induced response during HRE may play an important role in the long-term anabolic
      adaptation processes related to muscle hypertrophy and maximal strength
      development.

PMID- 16095405
TI  - Short vs. long rest period between the sets in hypertrophic resistance training:
      influence on muscle strength, size, and hormonal adaptations in trained men.
AB  - Acute and long-term hormonal and neuromuscular adaptations to hypertrophic
      strength training were studied in 13 recreationally strength-trained men. The
      experimental design comprised a 6-month hypertrophic strength-training period
      including 2 separate 3-month training periods with the crossover design, a
      training protocol of short rest (SR, 2 minutes) as compared with long rest (LR, 5
      minutes) between the sets. Basal hormonal concentrations of serum total
      testosterone (T), free testosterone (FT), and cortisol (C), maximal isometric
      strength of the leg extensors, right leg 1 repetition maximum (1RM), dietary
      analysis, and muscle cross-sectional area (CSA) of the quadriceps femoris by
      magnetic resonance imaging (MRI) were measured at months 0, 3, and 6. The 2
      hypertrophic training protocols used in training for the leg extensors (leg
      presses and squats with 10RM sets) were also examined in the laboratory
      conditions at months 0, 3, and 6. The exercise protocols were similar with regard
      to the total volume of work (loads x sets x reps), but differed with regard to
      the intensity and the length of rest between the sets (higher intensity and
      longer rest of 5 minutes vs. somewhat lower intensity but shorter rest of 2
      minutes). Before and immediately after the protocols, maximal isometric force and
      electromyographic (EMG) activity of the leg extensors were measured and blood
      samples were drawn for determination of serum T, FT, C, and growth hormone (GH)
      concentrations and blood lactate. Both protocols before the experimental training
      period (month 0) led to large acute increases (p < 0.05-0.001) in serum T, FT, C
      , and GH concentrations, as well as to large acute decreases (p < 0.05-0.001) in
      maximal isometric force and EMG activity. However, no significant differences
      were observed between the protocols. Significant increases of 7% in maximal
      isometric force, 16% in the right leg 1RM, and 4% in the muscle CSA of the
      quadriceps femoris were observed during the 6-month strength-training period.
      However, both 3-month training periods performed with either the longer or the
      shorter rest periods between the sets resulted in similar gains in muscle mass
      and strength. No statistically significant changes were observed in basal hormone
      concentrations or in the profiles of acute hormonal responses during the entire 6
      month experimental training period. The present study indicated that, within
      typical hypertrophic strength-training protocols used in the present study, the
      length of the recovery times between the sets (2 vs. 5 minutes) did not have an
      influence on the magnitude of acute hormonal and neuromuscular responses or long
      term training adaptations in muscle strength and mass in previously strength
      trained men.

PMID- 16095406
TI  - Measuring core stability.
AB  - In this study, a 4-item battery of core stability (CS) tests modeled on core
      stabilization activities used in training and rehabilitation research was
      developed, and a measurement schedule was established to maximize internal
      consistency and stability reliabilities. Specifically, we found that 4 test
      administrations on each of 4 days produced intraclass correlation coefficients
      that in most instances exceeded 0.90 and stability reliability coefficients on
      the third and fourth days of testing that exceeded 0.90 for 2 of the tests and
      0.80 for the other 2. Thus, it is recommended that in future research, examiners
      administer the battery for at least 3 days and consider the data collected on day
      3 as the best estimate of participant CS.

PMID- 16095407
TI  - The influence of grip width and forearm pronation/supination on upper-body
      myoelectric activity during the flat bench press.
AB  - The myoelectric signal of the sternoclavicular and clavicular portions of the
      pectoralis major, the biceps brachii, and the lateral head of triceps brachii of
      12 healthy men was collected during an isometric hold of 5 different bench press
      exercises. Grip width (narrow, mid, and wide) and the level of
      supination/pronation was varied to determine how these factors influence
      myoelectric amplitude during the flat bench press. A supinated grip resulted in
      increased activity for the biceps brachii and the clavicular portion of the
      pectoralis major. Additionally, moving from wide to narrower grip widths
      increased triceps activity and decreased the sternoclavicular portion of the
      pectoralis major. However, if the grip was supinated, moving to a narrower grip
      position did not result in a decrease in muscle activity of the sternoclavicular
      portion of the pectoralis major. The increase in triceps brachii activity when
      moving to a narrower grip width was not influenced by the level of supination.
      Considering the small changes that occur during changes in grip width, the choice
      of grip position should be determined by the positions athletes adopt during
      their sport. Sport specificity should supercede attempts to train specific muscle
      groups.

PMID- 16095408
TI  - A comparison of isoload and isoinertial leg press training on bone and muscle
      outcomes.
AB  - The subjects of this study (n = 20; 16 women, 4 men) performed 10 weeks of leg
      press training using one of two exercise modes (isoload or isotonic) with no
      crossover. Their workouts, which were performed 3 times per week, involved 4 sets
      of 8 repetitions with maximal voluntary effort. Testing was performed pre- and
      posttraining to examine bone and muscle changes. Posttraining, both groups
      incurred significant concentric knee extensor strength and leg muscle mass gains,
      while the percentage of body fat and total body fat mass each decreased. Leg and
      total body bone mineral densities showed group-by-time interactions, as isoload
      exercise caused posttraining gains, while isoinertial values were unchanged. Bone
      resorption assays showed insignificant changes. Isoload training likely involved
      greater strain magnitudes and rates to evoke higher peak forces and osteogenesis.
      Transduction of the training stimulus may have involved (a) formation in response
      to microdamage, and (b) piezoelectric-induced potentials that stimulated site
      specific osteoblast activity and osteogenesis.

PMID- 16095410
TI  - Physiological monitoring of cardiorespiratory adaptations during rehearsal and
      performance of contemporary dance.
AB  - Previous research has shown that dance class and rehearsal stress different
      cardiorespiratory energy systems than dance performance. The aim of the present
      study was to monitor the physiological parameters of a number of dancers during a
      12-week rehearsal period and an 8-week performance schedule. Seventeen dancers (8
      men and 9 women) from 2 companies undertook the multistage dance specific aerobic
      fitness test before the rehearsal period, before the performance period, and
      after the performance period. Heart rate data were collected throughout the test;
      the mean heart rate during stage 5 and blood lactate levels were measured at the
      end of the test. No significant changes in heart rate or lactate parameters were
      noted between the prerehearsal and preperformance tests, but significant
      decreases during the preperformance and postperformance tests were shown in both
      parameters (p < 0.01 and p < 0.01, respectively), which suggests an increase in
      the subjects' aerobic capacities during the performance period. Implications from
      the present study suggest that dancers are not adequately physiologically
      prepared to perform to the same degree to which their skills are honed. The study
      suggests that supplemental training is required to bridge this physical gap and
      better prepare the dancer for performance.

PMID- 16095409
TI  - "Psyching-up" enhances force production during the bench press exercise.
AB  - We investigated the effect of "psyching-up" on force production during the bench
      press. Twelve men (mean age +/- SD: 27.4 +/- 11.2 years) and 8 women (20.9 +/-
      2.5 years) with strength-training experience performed 5 bench press repetitions
      on a modified Biodex isokinetic dynamometer during 3 interventions. The
      interventions were counterbalanced and included a free-choice psych-up, a
      cognitive distraction, and an attention-placebo. Peak force recorded after
      psyching-up (mean +/- SD: 764 +/- 269 N.m) was significantly different from both
      distraction (703 +/- 282 N.m, p = 0.003) and attention-placebo (708 +/- 248 N.m,
      p = 0.01). The mean percentage increase in peak force from distraction to
      psyching-up was 11.8% (6 to 18%, 95% confidence interval [CI]) and 8.1% from
      placebo to psyching-up (3 to 13%, 95% CI). The results of the present study
      indicate that psyching-up may increase force production during the bench press
      exercise in participants with at least 1 year strength-training experience.

PMID- 16095411
TI  - Effects of hip flexor training on sprint, shuttle run, and vertical jump
      performance.
AB  - Although hip flexion is integral in sports, hip flexion exercises are seldom
      emphasized in strength and conditioning for sports performance. This study aimed
      to determine whether a hip flexor resistance-training program could improve
      performance on a variety of tasks. Thirteen men and 11 women completed an 8-week
      hip flexion resistance-training program. Eleven men and 13 women served as
      controls. Isometric hip flexion strength, 40-yd dash time and the time for the
      first 10-yds, 4 x 5.8-m shuttle run time, and vertical jump height were evaluated
      at the beginning and end of the training and control period. Improvements were
      observed in the training group but not in the control group. Individuals in the
      training group improved hip flexion strength by 12.2% and decreased their 40-yd
      and shuttle run times by 3.8% and 9.0%, respectively. An increase in hip flexion
      strength can help to improve sprint and agility performance for physically
      active, untrained individuals.

PMID- 16095412
TI  - Effect of post-tetanic potentiation of pectoralis and triceps brachii muscles on
      bench press performance.
AB  - The effect of post-tetanic potentiation (PTP) induced in the pectoralis and
      triceps brachii muscles by high-frequency submaximal percutaneous electrical
      stimulation (PES) on average and maximal power attained in bench press throwing
      was measured in 12 healthy men. Three PES regimens were used: (a) a 7-second and
      (b) a 10-second trial at 100 Hz, and (c) an intermittent trial with 8 1-second
      tetanic trains at 100 Hz with rest periods of 20 seconds. Only nonsignificant (p
      > 0.05) increase was observed in average power at 8 minutes and in maximal power
      at 5, 8, and 11 minutes after tetanus after 7-second trial, and in maximal power
      at 5 and 8 minutes after tetanus after an intermittent trial. These data indicate
      that PES application was a noneffective stimulus for increased bench press
      performance. A great interindividual variability response was observed and,
      therefore, PTP induction for improving upper-body muscle performance needs
      further experiments.

PMID- 16095413
TI  - Comparison of muscle activation using various hand positions during the push-up
      exercise.
AB  - Popular fitness literature suggests that varied hand placements during push-ups
      may isolate different muscles. Scientific literature, however, offers scant
      evidence that varied hand placements elicit different muscle responses. This
      study examined whether different levels of electromyographic (EMG) activity in
      the pectoralis major and triceps brachii muscles are required to perform push-ups
      from each of 3 different hand positions: shoulder width base, wide base, and
      narrow base hand placements. Forty subjects, 11 men and 29 women, performed 1
      repetition of each push-up. The EMG activity for subjects' dominant arm
      pectoralis major and triceps brachii was recorded using surface electrodes. The
      EMG activity was greater in both muscle groups during push-ups performed from the
      narrow base hand position compared with the wide base position (p < 0.05). This
      study suggests that, if a goal is to induce greater muscle activation during
      exercise, then push-ups should be performed with hands in a narrow base position
      compared with a wide base position.

PMID- 16095414
TI  - Influence of high-intensity interval training on adaptations in well-trained
      cyclists.
AB  - The purpose of the present study was to examine the influence of 3 different high
      intensity interval training regimens on the first and second ventilatory
      thresholds (VT(1) and VT(2)), anaerobic capacity (ANC), and plasma volume (PV) in
      well-trained endurance cyclists. Before and after 2 and 4 weeks of training, 38
      well-trained cyclists (Vo(2)peak = 64.5 +/- 5.2 ml.kg(-1).min(-1)) performed (a)
      a progressive cycle test to measure Vo(2)peak, peak power output (PPO), VT(1),
      and VT(2); (b) a time to exhaustion test (T(max)) at their Vo(2)peak power output
      (P(max)); and (c) a 40-km time-trial (TT(40)). Subjects were assigned to 1 of 4
      training groups (group 1: n = 8, 8 x 60% T(max) at P(max), 1:2 work-recovery
      ratio; group 2: n = 9, 8 x 60% T(max) at P(max), recovery at 65% maximum heart
      rate; group 3: n = 10, 12 x 30 seconds at 175% PPO, 4.5-minute recovery; control
      group: n = 11). The TT(40) performance, Vo(2)peak, VT(1), VT(2), and ANC were all
      significantly increased in groups 1, 2, and 3 (p < 0.05) but not in the control
      group. However, PV did not change in response to the 4-week training program.
      Changes in TT(40) performance were modestly related to the changes in Vo(2)peak,
      VT(1), VT(2), and ANC (r = 0.41, 0.34, 0.42, and 0.40, respectively; all p <
      0.05). In conclusion, the improvements in TT(40) performance were related to
      significant increases in Vo(2)peak, VT(1), VT(2), and ANC but were not
      accompanied by significant changes in PV. Thus, peripheral adaptations rather
      than central adaptations are likely responsible for the improved performances
      witnessed in well-trained endurance athletes following various forms of high
      intensity interval training programs.

PMID- 16095415
TI  - The accuracy of the American College of Sports Medicine metabolic equation for
      walking at altitude and higher-grade conditions.
AB  - The purpose of this study was to examine the accuracy of the American College of
      Sports Medicine (ACSM) walking equation at low walking speeds, altitude (1,550
      m), and higher grades. Twenty men and women (mean +/- SD, age, 28 +/- 6 years;
      height, 171 +/- 13 cm; weight, 67.8 +/- 18.1 kg) completed 2 randomized testing
      sessions under altitude (AL) (P(I)o(2) = 123.1 mm Hg [20.93%]) and sea level
      control (SLC) (P(I)o(2) = 147.3 mm Hg [25.00%]) conditions. Steady-state oxygen
      uptake (Vo(2)) was measured while subjects walked at 50 m.min(-1) at 8 separate
      grades (0, 5, 10, 15, 18, 21, 24, and 27%). Steady-state Vo(2) measurements from
      the last 2 minutes of each grade in AL and SLC were compared to the predicted
      Vo(2) of each grade according to the ACSM walking equation. Mean Vo(2)
      differences between predicted and AL values ranged from -0.5 to 1.4 ml.kg(
      1).min(-1), averaged -0.1 ml.kg(-1).min(-1) across all grades, and were
      significant (p < 0.05) at 0 percent grade. Mean Vo(2) differences between
      predicted and SLC values ranged from 0.6 to 3.0 ml.kg(-1).min(-1), averaged 1.4
      ml.kg(-1).min(-1) across all grades, and were statistically significant (p <
      0.05) at 0 and 5 percent. The standard error of the estimate (SEE) for the
      prediction of Vo(2) under AL and SLC were 2.2 and 2.0 ml.kg(-1).min(-1),
      respectively. Total errors for the prediction of Vo(2)max under AL and SLC were
      2.3 and 2.6 ml.kg(-1).min(-1), respectively. Overall, the findings indicate that
      the current ACSM prediction equation for walking is appropriate for application
      at low speeds, moderate altitude, and higher grades.

PMID- 16095416
TI  - A new non-exercise-based Vo2max prediction equation for aerobically trained men.
AB  - The purposes of the present study were to (a) modify previously published
      Vo(2)max equations using the constant error (CE = mean difference between actual
      and predicted Vo(2)max) values from Malek et al. (28); (b) cross-validate the
      modified equations to determine their accuracy for estimating Vo(2)max in
      aerobically trained men; (c) derive a new non- exercise-based equation for
      estimating Vo(2)max in aerobically trained men if the modified equations are not
      found to be accurate; and (d) cross-validate the new Vo(2)max equation using the
      predicted residual sum of squares (PRESS) statistic and an independent sample of
      aerobically trained men. One hundred and fifty-two aerobically trained men
      (Vo(2)max mean +/- SD = 4,154 +/- 629 ml.min(-1)) performed a maximal incremental
      test on a cycle ergometer to determine actual Vo(2)max. An aerobically trained
      man was defined as someone who had participated in continuous aerobic exercise 3
      or more sessions per week for a minimum of 1 hour per session for at least the
      past 18 months. Nine previously published Vo(2)max equations were modified for
      use with aerobically trained men. The predicted Vo(2)max values from the 9
      modified equations were compared to actual Vo(2)max by examining the CE, standard
      error of estimate (SEE), validity coefficient (r), and total error (TE). Cross
      validation of the modified non-exercise-based equations on a random subsample of
      50 subjects resulted in a %TE > or = 13% of the mean of actual Vo(2)max.
      Therefore, the following non-exercise-based Vo(2)max equation was derived from a
      random subsample of 112 subjects: Vo(2)max (ml.min(-1)) = 27.387(weight in kg) +
      26.634(height in cm) - 27.572(age in years) + 26.161(h.wk(-1) of training) +
      114.904(intensity of training using the Borg 6-20 scale) + 506.752(natural log of
      years of training) - 4,609.791 (R = 0.82, R(2) adjusted = 0.65, and SEE = 378
      ml.min(-1)). Cross-validation of this equation on the remaining sample of 40
      subjects resulted in a %TE of 10%. Therefore, the non-exercise-based equation
      derived in the present study is recommended for estimating Vo(2)max in
      aerobically trained men.

PMID- 16095417
TI  - The metabolic cost of hatha yoga.
AB  - To determine the metabolic and heart rate (HR) responses of hatha yoga, 26 women
      (19-40 years old) performed a 30-minute hatha yoga routine of supine lying,
      sitting, and standing asanas (i.e., postures). Subjects followed identical
      videotaped sequences of hatha yoga asanas. Mean physiological responses were
      compared to the physiological responses of resting in a chair and walking on a
      treadmill at 93.86 m.min(-1) [3.5 miles per hour (mph)]. During the 30-minute
      hatha yoga routine, mean absolute oxygen consumption (Vo(2)), relative Vo(2),
      percentage maximal oxygen consumption (%Vo(2)R), metabolic equivalents (METs),
      energy expenditure, HR, and percentage maximal heart rate (%MHR) were 0.45 L.min(
      1), 7.59 ml.kg(-1).min(-1), 14.50%, 2.17 METs, 2.23 kcal.min(-1), 105.29 b.min(
      1), and 56.89%, respectively. When compared to resting in a chair, hatha yoga
      required 114% greater O(2) (L.min(-1)), 111% greater O(2)(ml.kg(-1).min(-1)),
      4,294% greater %Vo(2)R, 111% greater METs, 108% greater kcal.min(-1), 24% greater
      HR, and 24% greater %MHR. When compared to walking at 93.86 m.min(-1), hatha yoga
      required 54% lower O(2)(L.min(-1)), 53% lower O(2)(ml.kg(-1).min(-1)), 68% lower
      %Vo(2)R, 53% lower METs, 53% lower kcal.min(-1), 21% lower HR, and 21% lower
      %MHR. The hatha yoga routine in this study required 14.50% Vo(2)R, which can be
      considered a very light intensity and significantly lighter than 44.8% Vo(2)R for
      walking at 93.86 m.min(-1) (3.5 mph). The intensity of hatha yoga may be too low
      to provide a training stimulus for improving cardiovascular fitness. Although
      previous research suggests that hatha yoga is an acceptable form of physical
      activity for enhancing muscular fitness and flexibility, these data demonstrate
      that hatha yoga may have little, if any, cardiovascular benefit.

PMID- 16095418
TI  - Effect of continuous passive motion (machine-assisted) exercise as an alternative
      form of training on physiological profiles of women aged 40-65 years.
AB  - The purpose of this study was to determine the effectiveness of 16 weeks of
      continuous passive motion (CPM) or machine-assisted exercise as an alternative
      form of training on body composition, muscle strength, and flexibility in women
      aged 40-65 years. Thirty-one exercisers and 8 controls completed 16 weeks of
      training, with the exercisers averaging 3 sessions per week. Six toning tables
      targeted different muscle groups by moving the body and/or limbs while subjects
      attempted to resist the movements. Body composition was assessed by individual
      measures (dual energy x-ray absorptiometry, hydrodensitometry, and bioelectric
      impedance) and a 4-compartment model, flexibility was assessed by a Leighton
      flexometer and the sit and reach procedure, and strength was measured by standard
      1 repetition maximum procedures before training began, after 5 weeks of training,
      and after 16 weeks of training. When the 2 groups were compared after week 5 and
      week 16 of training, few significant (p < 0.05) group by trial differences were
      noted; however, these differences were minimal and represented little or no
      practical significance (very low effect sizes). In conclusion, CPM training did
      not appear to provide a sufficient stimulus to significantly alter measures of
      strength, flexibility, or body composition in women aged 40-65 years.

PMID- 16095419
TI  - Short-term effects of electrical stimulation superimposed on muscular voluntary
      contraction in postural control in elderly women.
AB  - Thirty-two women between 62 and 75 years old were randomized into 3 groups. Each
      group performed a program of 4 sessions a week over 6 weeks. Group SC (n = 11)
      climbed up and down stairs, group ES (n = 11) practiced electrostimulation, and
      group SC + ES (n = 10) superimposed the 2 activities simultaneously. Using a
      force platform and a seesaw platform, static and dynamic balance in eyes-open and
      eyes-closed conditions were analyzed before and after the programs for each
      group. After the programs, the results indicated that dynamic balance improved
      for the 3 groups, but the contribution of visual information in the control of
      oscillation amplitude was lower in the SC group than in the ES and SC + ES
      groups. In the SC + ES group, the electrical stimulation interferes with
      neurophysiologic afference integration in postural control in relation to
      voluntary movement. Voluntary exercise appears to be more efficient than
      electrical stimulation and the superimposed techniques to change balancing
      tactics in the elderly.

PMID- 16095420
TI  - The benefits of a functional exercise circuit for older adults.
AB  - The physical benefits of a functional exercise circuit are not well known in an
      elderly population. The purpose of this study was to evaluate the effect of a
      functional exercise circuit on mobility and perceived health in the elderly.
      Subjects were 119 men and women (aged 74 [+/-4.2] years) who received pre- and
      posttests of mobility (e.g., sit to stand, get up and go, timed walk),
      flexibility (sit and reach), and balance (standing reach) and who completed the
      Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). A supervised
      functional exercise circuit that included 10 different upper- and lower-body
      exercises performed under time constraints was performed 3 times per week for 12
      consecutive weeks. Paired t-tests showed significant differences at posttest for
      the get up and go (p < 0.001), standing reach (p < 0.001), sit and reach (p <
      0.001), and selected items from the SF-36, including physical functioning (p <
      0.001), pain (p = 0.001), vitality (p = 0.001), and number of doctor visits (p <
      0.001). A functional exercise circuit such as the one employed in this study may
      offer promise as an effective means of promoting mobility and perceived health in
      older adults.

PMID- 16095421
TI  - Effects of a heavy and a moderate resistance training on functional performance
      in older adults.
AB  - Resistance training can improve strength and functional performance, but there is
      little information about the effect of training intensity on functional
      performance in older adults. The purpose of this study was to determine the
      effect of 12 weeks of heavy (80% of 1 repetition maximum [1RM]) and moderate (60%
      of 1RM) resistance training on functional performance in healthy, inactive older
      adults, ages 60-74 years. Volunteer subjects were assigned randomly to a control
      group (CS, n = 10), heavy resistance training group (HRT, n = 11), or moderate
      resistance training group (MRT, n = 12) and participated in 12 weeks of strength
      training, 3 times per week. Performance measurements included 1RM lower-body
      strength, chair-rising time, walking velocity, stair-climbing time, and
      flexibility. Significant differences between HRT and MRT were found for 1RM
      strength of the lower limbs after the training period. Functional performance
      improved similarly for both HRT and MRT after the training period. Functional
      performance can be improved significantly with either heavy or moderate
      resistance training, without significant differences in the effectiveness of the
      2 training protocols.

PMID- 16095422
TI  - Relationship between the 30-second wingate test and characteristics of isometric
      and explosive leg strength in young subjects.
AB  - The aim of this study was to investigate a possible relation between power
      performance of the Wingate test (WT) and isometric leg strength (ILS) and
      explosive leg strength (ELS) characteristics in young men and women with
      different physical fitness levels. A total of 166 subjects, including 98 young
      men and 68 young women, were included in the study. The subjects were divided
      into a regular exercise group and a sedentary group. The physical and body mass
      index characteristics of the subjects were not different, and they had not taken
      part in the directed jumping. When the regular exercise and sedentary groups were
      considered together with men, women, and total population groups, no significant
      correlation existed between WT anaerobic fatigue index and ILS and ELS (p >
      0.05), but significant positive correlations existed among peak power, peak power
      per weight, mean power, mean power per weight, and WT power, which were recorded
      in 5-second intervals (p < 0.001). Although the 5-second WT parameters were
      significantly correlated with ILS and ELS for the first 15-second period, this
      correlation was more pronounced for the last 15 seconds for all groups (p <
      0.01). As a result, this study indicated that regular physical activity has a
      positive significant relation on WT power, ILS, and ELS in both sedentary men and
      women and those engaged in regular sports activities.

PMID- 16095423
TI  - Effects of strength training on body composition and bone mineral content in
      children who are obese.
AB  - The purpose of this study was to test the hypothesis that strength training
      benefits diet-controlled obese children with respect to lean mass and bone
      mineral acquisition. Eighty-two Hong Kong school children (aged 10.4 +/- 1.0
      years, 70 in Tanner stage 1, 12 in stage 2) who were obese/overweight were
      randomly assigned to receive either a balanced low-energy (900-1200 cal) diet
      plus strength training (n = 41) (training group) or the diet alone (n = 41)
      (control group). The training group attended a 75-minute strength exercise
      program 3 times/week for 6 weeks (phase 1), after which they were offered and 22
      children opted to continue a once-weekly program for a further 28 weeks (phase
      2). All children were evaluated at baseline, after 6 weeks, and at the end of the
      36-week study (including an intervening 2-week introduction to phase 2). Body
      composition and bone mineral content were measured by dual-energy X-ray
      absorptiometry, and diet was assessed by food-frequency questionnaire. The
      results showed that the exercise programs were well accepted, with good
      attendance at the exercise classes. After 6 weeks, the children in the training
      group showed significantly larger increases in lean body mass (+ 0.8 kg [2.4%]
      vs. +0.3 kg [1.0%], p < 0.05) and total bone mineral content (+46.9 g [3.9%] vs.
      +33.6 g [2.9%], p < 0.05) than those in the control group. At the end of the
      study, these trends were maintained in the continued-training subgroup, though no
      longer reaching statistical significance. We conclude that in diet-controlled
      prepubertal obese/overweight children, participation in an exercise program with
      emphasis on strength training resulted in improved lean mass and bone mineral
      accrual.

PMID- 16095424
TI  - The best warm-up for the vertical jump in college-age athletic men.
AB  - The purpose of this study was to determine the effectiveness of specific and
      nonspecific warm-ups on the vertical jump test performed by athletic men. Twenty
      nine men (18-23 years) in athletics (speed positions in football) performed
      vertical jump tests on 4 separate days after completing 4 different warm-up
      protocols. The 4 warm-up protocols were (a) submaximal jump warm-up, (b) weighted
      jump warm-up, (c) stretching warm-up, and (d) no warm-up. The weighted jump warm
      up protocol required 5 countermovement jumps onto a box, with the athletes
      holding dumbbells equaling 10% of their body weight. The submaximal jump warm-up
      protocol required the athletes to perform 5 countermovement jumps at 75%
      intensity of their past maximum vertical jump score. The stretching warm-up
      protocol required the athletes to perform 14 different stretches, each held for
      20 seconds. The no warm-up protocol required the athletes to perform no activity
      prior to being tested. Three vertical jumps were measured following each warm-up;
      the score for analysis was the best jump. The data were analyzed with a repeated
      measures analysis of variance and Bonferroni post hoc tests. The Bonferroni post
      hoc tests showed a significant difference (p < 0.001) between the weighted jump
      warm-up and all other warm-ups. The effect size was 0.380 and the power was 1.00
      for the statistical analyses. We concluded that utilizing a weighted resistance
      warm-up would produce the greatest benefit when performing the vertical jump
      test.

PMID- 16095425
TI  - Effects of static stretching for 30 seconds and dynamic stretching on leg
      extension power.
AB  - The purposes of this study were to clarify the effects of static stretching for
      30 seconds and dynamic stretching on leg extension power. Eleven healthy male
      students took part in this study. Each subject performed static stretching and
      dynamic stretching on the 5 muscle groups in the lower limbs and nonstretching on
      separate days. Leg extension power was measured before and after the static
      stretching, dynamic stretching, and nonstretching. No significant difference was
      found between leg extension power after static stretching (1788.5 +/- 85.7 W) and
      that after nonstretching (1784.8 +/- 108.4 W). On the other hand, leg extension
      power after dynamic stretching (2022.3 +/- 121.0 W) was significantly (p < 0.01)
      greater than that after nonstretching. These results suggest that static
      stretching for 30 seconds neither improves nor reduces muscular performance and
      that dynamic stretching enhances muscular performance.

PMID- 16095426
TI  - Surface electromyographic assessment of the effect of static stretching of the
      gastrocnemius on vertical jump performance.
AB  - The purpose of this study was to investigate the effects of static stretching of
      the gastrocnemius muscle on maximal vertical jump performance using
      electromyographic activity (EMG) of the gastrocnemius musculature to record
      muscle activation during vertical jump performance. Fourteen healthy adults (8
      men and 6 women) aged 18-34 years, who were familiar with the vertical jumping
      task and had no lower extremity injuries or any bone or joint disorders within
      the past year, served as participants for this study. After a brief warm-up,
      participants performed the following sequence: (a) three baseline maximal
      vertical jump trials, (b) 15 minutes of quiet sitting and three 30-second
      bilateral static stretches of the gastrocnemius muscles, and (c) 3 maximal
      vertical jump trials. Jump height data were collected using the Kistler force
      plate, while muscle activity was recorded during the jumping and stretching
      trials using a Noraxon telemetry EMG unit. Vertical jump height data as well as
      EMG values were averaged for the 3 trials and analyzed using paired t-tests for
      pre- and poststretching (alpha = 0.05). Vertical jump height was 5.6% lower when
      poststretch heights were compared with prestretch heights (t = -4.930, p <
      0.005). Gastrocnemius EMG was 17.9% greater when the EMG during poststretch jumps
      was compared with prestretch jumps (t = 2.805, p < 0.02). The results from this
      study imply that, despite increased gastrocnemius muscle activity, static
      stretching of the gastrocnemius muscles had a negative effect on maximal jumping
      performance. The practical importance concerns coaches and athletes, who may want
      to consider the potential adverse effects of performing static stretching of the
      gastrocnemius muscles only before a jumping event, as jump height may be
      negatively affected. Future research is required to identify the mechanisms that
      affect vertical jump performance.

PMID- 16095427
TI  - Moderate resistance training volume produces more favorable strength gains than
      high or low volumes during a short-term training cycle.
AB  - The purpose of this study was to examine the effects of 3 resistance training
      volumes on maximal strength in the snatch (Sn), clean & jerk (C&J), and squat
      (Sq) exercises during a 10-week training period. Fifty-one experienced (>3
      years), trained junior lifters were randomly assigned to one of 3 groups: a low
      volume group (LVG, n = 16), a moderate-volume group (MVG, n = 17), and a high
      volume group (HVG, n = 18). All subjects trained 4-5 days a week with a
      periodized routine using the same exercises and relative intensities but a
      different total number of sets and repetitions at each relative load: LVG (1,923
      repetitions), MVG (2,481 repetitions), and HVG (3,030 repetitions). The training
      was periodized from moderate intensity (60- 80% of 1 repetition maximum [1RM])
      and high number of repetitions per set (2-6) to high intensity (90-100% of 1RM)
      and low number of repetitions per set (1-3). During the training period, the MVG
      showed a significant increase for the Sn, C&J, and Sq exercises (6.1, 3.7, and
      4.2%, respectively, p < 0.01), whereas in the LVG and HVG, the increase took
      place only with the C&J exercise (3.7 and 3%, respectively, p < 0.05) and the Sq
      exercise (4.6%, p < 0.05, and 4.8%, p < 0.01, respectively). The increase in the
      Sn exercise for the MVG was significantly higher than in the LVG (p = 0.015).
      Calculation of effect sizes showed higher strength gains in the MVG than in the
      HVG or LVG. There were no significant differences between the LVG and HVG
      training volume-induced strength gains. The present results indicate that junior
      experienced lifters can optimize performance by exercising with only 85% or less
      of the maximal volume that they can tolerate. These observations may have
      important practical relevance for the optimal design of strength training
      programs for resistance-trained athletes, since we have shown that performing at
      a moderate volume is more effective and efficient than performing at a higher
      volume.

PMID- 16095428
TI  - Influence of different relative intensities on power output during the hang power
      clean: identification of the optimal load.
AB  - The influence of different relative intensities on power output was investigated
      in the present study in order to identify the optimal load that maximizes power
      output during the hang power clean. Fifteen men (age: 22.1 +/- 2.0 years, height:
      180.1 +/- 6.3 cm, and body mass: 89.4 +/- 14.7 kg) performed the hang power
      cleans on a forceplate at 30-90% of one repetition maximum (1RM). Peak power was
      maximized at 70% 1RM, which was, however, not significantly different from peak
      power at 50, 60, 80, and 90% 1RM. Average power also was maximized at 70% 1RM,
      which was not significantly different from average power at 40, 50, 60, 80, and
      90% 1RM. It was concluded that (a) the relative intensity had a significant
      influence on power output, and (b) power output can be maximized at a submaximal
      load during the hang power clean.

PMID- 16095429
TI  - Abdominal strengthening using the AbVice machine as measured by surface
      electromyographic activation levels.
AB  - Twenty-four college students served as subjects in a study that examined the
      effect of a prototypical abdominal muscle strengthening device (AbVice) compared
      with other devices currently on the market. The purpose of the present study was
      to investigate a prototypical device (AbVice) that incorporates contraction of
      the hamstring and gluteal musculature in conjunction with the abdominals, which
      may assist in decreasing activation of the hip flexors by allowing greater
      activity levels of the abdominal musculature via the theory of reflex inhibition,
      compared with other devices currently available on the market (AbRoller and
      AbRocker). The repeated-measures study included 17 women and 7 men who ranged in
      age from 20-23 years (mean +/- SD age, 21.3 +/- 1.5 years). Each subject
      underwent a single session of data collection during which they completed 10
      repetitions of abdominal crunches per device. Subjects completed 4 different
      crunch sets (AbRocker, AbRoller, standard crunch, AbVice). Counterbalancing of
      the device was used to negate the effect of fatigue. Speed of repetitions was
      ensured via use of a metronome set at 40 b.min(-1) to permit similar contraction
      times and rest periods between repetitions. Rest between conditions was 3
      minutes. Mean activation levels of surface electromyography (EMG) were recorded
      for each condition at the following locations on the right side of the body:
      rectus abdominis 2.5 cm superior to the umbilicus, rectus abdominis 2.5 cm
      inferior to the umbilicus, external oblique abdominis 1.0 cm medial to the
      anterior superior iliac spine, and external oblique abdominis less than 1.0 cm
      superior to the inguinal ligament. Mean (SD) activation was 1,165.21 mV (634.60
      mV) with the AbVice, 242.92 mV (263.03 mV) with the AbRocker, 753.29 mV (514.80
      mV) with the standard crunch, and 757.67 mV (542.85 mV) with the AbRoller. Broken
      down by sex, women had the following mean (SD) EMG values: 1,079.76 mV (705.02
      mV) with the AbVice, 680.35 mV (535.35 mV) with the standard crunch, 262.70 mV
      (305.89 mV) with the AbRocker, and 636.88 mV (502.82 mV) with the AbRoller. Men
      demonstrated mean (SD) values of 1,372 mV (383.87 mV) with the AbVice, 1,051 mV
      (560.09 mV) with the AbRoller, 930.43 mV (447.17 mV) with the standard crunch,
      and 194.86 mV (109.05 mV) with the AbRocker. Two-way analysis of variance with
      factor 1 (person) and factor 2 (condition) had F values of 11.73 and 36.04,
      respectively. Post hoc analysis using the Tukey test indicated that all
      comparisons between conditions were significant at the p = 0.01 level except for
      the standard crunch vs. the AbRoller. The AbVice activated the selected abdominal
      musculature more effectively than the other conditions.

PMID- 16095430
TI  - Pre- and post-game body mass changes during an international rugby tournament: a
      practical perspective.
AB  - Pre- and post-game body mass changes were recorded throughout an international
      rugby union tournament to determine changes in body mass when training and
      competing on consecutive days. A squad of 28 players with a mean (+/-SD) age of
      20.0 yrs (+/-0.6), height of 1.85 m (+/-0.1) and body mass of 94.71 kg (+/-10.71)
      were selected to play for England and to participate in an international
      championship in Sydney, Australia. From the squad, 22 players played in 1 or more
      of 4 games over a 10-day period from the day of the first match to the day of the
      last match. Data were collected for a total of 84 player appearances across the 4
      games. Players had their body masses recorded prior to leaving England, upon
      arrival in Australia, and pre- and post-game during the tournament. Players were
      allowed to ingest fluid ad libitum throughout each match. The mean (+/-SD)
      ambient temperature and relative humidity across all games was 18.5 degrees C (+/
      1.63) and 39.5% (+/-17.7), respectively. Pre- and post-game comparisons of body
      masses for all player appearances were significantly different (p < 0.00),
      representing a mean loss of 0.94 kg (+/-0.94). However, there was no significant
      difference between games or player position (forwards vs. backs). The results
      demonstrate that if appropriate hydration practices are implemented, they may
      reduce the compound effect of fluid loss when playing multiple games in a short
      period of time. Strategies include daily monitoring of body mass and fluid intake
      and educating players about the importance of fluid intake to recovery and
      subsequent performance when playing and training on consecutive days.

PMID- 16095431
TI  - Reliability and validity of three strength measures obtained from community
      dwelling elderly persons.
AB  - The purpose of this study was to describe the reliability and validity of 3
      strength measures obtained from community-dwelling elderly individuals. The
      strength of 10 elders was tested initially and 6 and 12 weeks later using the
      MicroFET 2 hand-held dynamometer (knee extension strength), the Jamar dynamometer
      (grip strength), and the sit-to-stand (STS) test. Mobility was tested using the
      timed up-and-go (TUG) test and a timed walk test. Intraclass correlation
      coefficients, which were used to characterize the reliability of the strength
      tests, ranged from 0.807 to 0.981. Pearson correlations between the lower
      extremity strength measures and the TUG and gait speed ranged from 0.635 to 
      0.943. Our examination of the 3 measures for 12 weeks extends previous evidence
      of the stability of these strength measures and justifies the use of hand-held
      dynamometry and the STS test when investigating limitations in mobility.

PMID- 16095432
TI  - Mentoring, clinical supervision and preceptoring: clarifying the conceptual
      definitions for Australian rural nurses. A review of the literature.
AB  - In Australia, mentoring is beginning to emerge on the rural and remote nursing
      landscape as a strategy to improve the recruitment and retention of nurses.
      However, the terminology used to discuss this and other supportive relationships
      in nursing is often unclear and can be confusing. The main aim of this article is
      to locate mentoring, clinical supervision and preceptoring in the nursing
      literature, and thus provide a guide for Australian rural nurse clinicians,
      managers and policy-makers in general. It is through better understanding of the
      possibilities of each type of relationship that they can be factored into the
      development of supportive work settings, and that will encourage the retention of
      existing staff and possibly the recruitment of new staff. Each type of supportive
      relationship discussed in the literature has a different focus. Mentoring is
      broadly based and concentrates on developing areas such as career progression,
      scholarly achievements and personal development. Clinical supervision focuses on
      progressing clinical practice through reflection and the provision of
      professional guidance and support. Preceptorship focuses on clinical skill
      acquisition and socialisation. Each support relationship also differs in context
      and intensity. Mentoring relationships are based around developing reciprocity
      and accountability between each partner. They are normally conducted outside the
      work environment and in the participants' own time. Clinical supervisory
      relationships are similar to mentoring in that they are reliant on developing a
      strong sense of reciprocity and accountability, and take place over a long period
      of time. They differ, though, in that they are conducted during working hours,
      although preferably away from the work setting. They are also commonly
      facilitated through the use of small groups. Preceptoring relationships are short
      term, exist in the clinical context and concentrate on clinical skill acquisition
      and assessment.

PMID- 16095433
TI  - Univariate solutions in a multivariate world: can we afford to practice as in the
      "good old days"?

PMID- 16095434
TI  - A meta-analysis of interventions to improve care for chronic illnesses.
AB  - OBJECTIVE: To use empirical data from previously published literature to address
      2 research questions: (1) Do interventions that incorporate at least 1 element of
      the Chronic Care Model (CCM) result in improved outcomes for specific chronic
      illnesses? (2) Are any elements essential for improved outcomes? STUDY DESIGN:
      Meta-analysis. METHODS: Articles were identified from narrative literature
      reviews and quantitative meta-analyses, each of which covered multiple
      bibliographic databases from inception to March 2003. We supplemented this
      strategy by searching the MEDLINE database (1998-2003) and by consulting experts.
      We included randomized and nonrandomized controlled trials of interventions that
      contained 1 or more elements of the CCM for asthma, congestive heart failure
      (CHF), depression, and diabetes. We extracted data on clinical outcomes, quality
      of life, and processes of care. We then used random-effects modeling to compute
      pooled standardized effect sizes and risk ratios. RESULTS: Of 1345 abstracts
      screened, 112 studies contributed data to the meta-analysis: asthma, 27 studies;
      CHF, 21 studies; depression, 33 studies; and diabetes, 31 studies. Interventions
      with at least 1 CCM element had consistently beneficial effects on clinical
      outcomes and processes of care across all conditions studied. The effects on
      quality of life were mixed, with only the CHF and depression studies showing
      benefit. Publication bias was noted for the CHF studies and a subset of the
      asthma studies. CONCLUSIONS: Interventions that contain at least 1 CCM element
      improve clinical outcomes and processes of care--and to a lesser extent, quality
      of life--for patients with chronic illnesses.

PMID- 16095435
TI  - Implementation of an inpatient management and discharge strategy for patients
      with community-acquired pneumonia.
AB  - OBJECTIVE: To assess the effectiveness and safety of implementing an inpatient
      management and discharge strategy based on empiric antibiotic therapy with
      ceftriaxone sodium and a guideline to promote timely discharge for clinically
      stable patients hospitalized with community-acquired pneumonia. STUDY DESIGN: A
      cluster randomized controlled clinical trial with 30 days of patient follow-up at
      8 teaching hospitals and 17 nonteaching hospitals nationwide. METHODS:
      Participants included 240 intervention patients and 209 control patients admitted
      by 85 physician groups between December 1998 and December 1999. Within each
      hospital, defined physician practice groups were randomized to the intervention
      arm (physician notification coupled with ceftriaxone sodium as empiric therapy)
      or control arm (neither component). Physicians in the intervention arm were
      notified when their patients met guideline criteria for clinical stability;
      physicians in the control arm were not contacted. RESULTS: The median length of
      stay was 4 days in both study arms. The observed reduction in costs associated
      with the intervention was not statistically significant when cost outliers were
      excluded. Mortality, serious adverse event, and rehospitalization rates did not
      differ significantly across study arms. CONCLUSIONS: Implementation of an
      inpatient management strategy based on physician reminders coupled with empiric
      use of ceftriaxone sodium did not reduce length of stay or associated medical
      care costs for patients hospitalized with community-acquired pneumonia. These
      negative findings are most likely due to insufficient potency of the
      intervention, inadequate guideline implementation, or imbalances in baseline
      patient characteristics.

PMID- 16095436
TI  - Recruiting health plan members receiving pharmacotherapy into smoking cessation
      counseling.
AB  - BACKGROUND: Smokers receiving pharmacotherapy and individualized smoking
      cessation counseling through telephone quitlines have been found to have higher
      quit rates than smokers receiving pharmacotherapy alone. Health plans are often
      positioned to encourage their members to use quitline services in addition to
      pharmacotherapy. OBJECTIVE: To determine if healthcare members who were receiving
      pharmacotherapy increased their participation in smoking quitline services after
      receiving proactive telephone calls or postcards. STUDY DESIGN: Randomized
      controlled trial. METHODS: Health plan members filing pharmacotherapy claims were
      identified weekly from health plan pharmacy claims data and randomized to 1 of
      the following 3 conditions: control, recruitment postcard, or recruitment
      telephone call by a nurse quitline counselor. Enrollment of study members into
      the quitline program was tracked for 1 month after randomization. RESULTS: During
      5 months, 625 individuals were identified for participation in the study, with
      the following enrollment into the program: 0% to the control group, 1.3% to the
      postcard group, and 20.6% to the telephone call group (P < .001 for significance
      by group). Although costs for the telephone intervention were the most expensive,
      it was also the most cost effective, given its success in enrolling members into
      the program. CONCLUSIONS: Proactive telephone calling by smoking cessation nurse
      counselors to smokers receiving pharmacotherapy may be an effective method of
      enrolling smokers into a cessation quitline. Health plans should consider
      proactive telephone recruitment to improve use of quitline services.

PMID- 16095437
TI  - Identifying highly effective psychotherapists in a managed care environment.
AB  - OBJECTIVE: To investigate the variability and stability of psychotherapists'
      effectiveness and the implications of this differential effectiveness for quality
      improvement in a managed care environment. STUDY DESIGN: Subset archival outcome
      data for patients receiving behavioral health treatment were divided into 2 time
      periods to cross-validate the treating therapists' effectiveness. After
      categorizing the therapists as "highly effective" and "others" during the
      baseline period, the stability of their individual effectiveness was cross
      validated in the remaining time period. METHODS: Outcomes for 10 812 patients
      (76.0% adults, 24.0% children and adolescents) treated by 281 therapists were
      included. Patients initiated treatment between January 1999 and June 2004. Mean
      residual change scores obtained by multiple regression were used to adjust for
      differences in case mix among therapists. Raw change scores as well as mean
      residualized change scores were compared between the 71 psychotherapists
      identified as highly effective (25%) and those identified as other (remaining
      75%). RESULTS: During the cross-validation period, mean differences in
      residualized change score between highly effective therapists and others were
      statistically significant (difference = 2.8; P < .001), which corresponded to an
      average of 53.3% more change in raw change scores with the highly effective
      therapists. Results could not be explained by case mix differences in diagnosis,
      age, sex, intake scores, prior outpatient treatment history, length of treatment,
      or therapist training/experience. CONCLUSION: Behavioral health outcomes for a
      large system of care could be significantly improved by measuring clinical
      outcomes and referring patients to therapists with superior outcomes.

PMID- 16095438
TI  - The relationship between quality and utilization in managed care.
AB  - OBJECTIVE: To examine correlations of commercial health plan performance on
      Health Plan Employer Data and Information Set (HEDIS) effectiveness-of-care
      measures with utilization rates, as a proxy for cost. STUDY DESIGN: Cross
      sectional study of 254 commercial health plans. METHODS: This report used data
      reported by commercial managed care plans in the 2003 HEDIS dataset. Utilization
      measures included access to care (the proportion of adults with at least 1
      primary care or preventive visit), outpatient use (the number of outpatient
      visits per 1000 members per year), inpatient discharges (the number of inpatient
      discharges for medical conditions per 1000 members per year), and inpatient days
      (inpatient hospital days for medical conditions per 1000 members per year). A
      composite quality score was calculated from HEDIS indicators. Estimates of health
      plan membership demographics were identified from Consumer Assessment of Health
      Plans (CAHPS) survey data. Of 316 reporting plans, 254 reported sufficient data
      to be included in this analysis. Bivariate correlations and multivariate
      regressions (controlling for health plan and membership characteristics) were
      conducted. RESULTS: Quality was positively correlated with access to outpatient
      care (r = 0.46, P < .001), negatively associated with inpatient days (r = -0.30,
      P < .001), and not associated with total outpatient visits (r = 0.04, not
      significant). Regression results controlling for selected plan and member
      characteristics demonstrated similar findings. CONCLUSIONS: Although the
      mechanism of this cross-sectional association is unclear, these data provide
      important starting points for further research on the interrelationships of
      quality and resource use.

PMID- 16095440
TI  - Pre-operative fasting guidelines: an update.
AB  - Liberal pre-operative fasting routines have been implemented in most countries.
      In general, clear fluids are allowed up to 2 h before anaesthesia, and light
      meals up to 6 h. The same recommendations apply for children and pregnant women
      not in labour. In children <6 months, most recommendations now allow breast- or
      formula milk feeding up to 4 h before anaesthesia. Recently, the concept of pre
      operative oral nutrition using a special carbohydrate-rich beverage has also
      gained support and been shown not to increase gastric fluid volume or acidity.
      Based on the available literature, our Task Force has produced new consensus
      based Scandinavian guidelines for pre-operative fasting. What is still not clear
      is to what extent the new liberal fasting routines should apply to patients with
      functional dyspepsia or systematic diseases such as diabetes mellitus. Other
      still controversial areas include the need for and effect of fasting in emergency
      patients, women in labour and in association with procedures done under 'deep
      sedation'. We think more research on the effect of various fasting regimes in
      subpopulations of patients is needed before we can move one step further towards
      completely evidence-based pre-operative fasting guidelines.

PMID- 16095439
TI  - Nogo-B is a new physiological substrate for MAPKAP-K2.
AB  - The neurite outgrowth inhibitor protein Nogo is one of 300 proteins that contain
      a reticulon homology domain, which is responsible for their association with the
      endoplasmic reticulum. Here we have found that the Nogo-B spliceform becomes
      phosphorylated at Ser107 in response to lipopolysaccharide in RAW264 macrophages
      or anisomycin in HeLa cells. The phosphorylation is prevented by SB 203580, an
      inhibitor of SAPK2a (stress-activated protein kinase 2a)/p38a and SAPK2b/p38b,
      and does not occur in embryonic fibroblasts generated from SAPK2a/p38a-deficient
      mice. Nogo-B is phosphorylated at Ser107 in vitro by MAPKAP-K2 [MAPK (mitogen
      activated protein kinase)-activated protein kinase-2] or MAPKAP-K3, but not by
      other protein kinases that are known to be activated by SAPK2a/p38a. The
      anisomycin-induced phosphorylation of Ser107 in HeLa cells can be prevented by
      'knockdown' of MAPKAP-K2 using siRNA (small interfering RNA). Taken together, our
      results identify Nogo-B as a new physiological substrate of MAPKAP-K2.

PMID- 16095441
TI  - Continuous peripheral nerve blockade in lower extremity surgery.
AB  - Peripheral nerve blocks afford numerous benefits for lower extremity surgery.
      There is growing interest in continuous peripheral nerve blocks, mainly for
      treatment of postoperative pain, a field that represents a challenge to the
      anaesthesiologist. This paper seeks to review the efficacy of continuous lower
      limb blocks for postoperative pain relief. Not only do continuous peripheral
      nerve blocks afford specificity of analgesic area but current research has shown
      that they enhance postoperative analgesia and patient satisfaction. New
      techniques and devices are increasingly appearing, and catheters are constantly
      being developed and improved; an example being the stimulating catheter, which
      represents one of the newest advances in this area. The above techniques show
      that continuous postoperative analgesia with catheters in the lower extremities
      is not only possible, but indeed provides sustained effective postoperative
      analgesia, reduces use of opioids, and improves rehabilitation and patient well
      being with minimal side-effects. These techniques could prove an alternative to
      postoperative pain treatment following ambulatory surgery.

PMID- 16095443
TI  - Inter-observer agreement of tests used for prediction of difficult
      laryngoscopy/tracheal intubation.
AB  - BACKGROUND: Guidelines recommend pre-operative airway evaluation for the
      prediction of airway management difficulties. Combining tests for evaluation
      increases the accuracy of the assessment. One model including seven parameters
      transformed into a simplified airway risk index (SARI) has been proven to be
      valid. We determined the inter-observer agreement of the specific test
      combinations included in SARI as well as of the total score. METHODS: Four
      observers assessed 136 patients, 120 without and 16 with a difficult airway
      history. Two residents and two specialists in anaesthesia performed the airway
      assessment consisting of the measurement of the mouth opening, the thyromental
      distance (TMD), the ability to protrude the mandible and an evaluation of the
      Mallampati class and head and neck mobility. Body weight was also recorded. Inter
      observer agreement between specialists and residents, separately, was analysed
      using kappa statistics and Spearman's correlation analysis and the limits of
      agreement were evaluated using the 95% confidence interval. The agreement between
      pairs of assessors was also evaluated. RESULTS: The inter-observer agreement was
      good to excellent for both specialists and residents when measuring mouth opening
      (Spearman's correlation coefficient R=0.88-0.97) and the horizontal distance
      between the upper and lower incisors during jaw protrusion (R=0.56-0.97). The
      Mallampati classification assessment demonstrated satisfactory to complete inter
      observer agreement (kappa=0.41-1). The assessment of TMD and neck mobility showed
      considerable discrepancies between observers. CONCLUSIONS: We demonstrated good
      inter-observer agreement using three tests from SARI and recommend the Mallampati
      classification, mouth opening and ability of jaw protrusion for pre-operative
      airway evaluation. A simplification of the assessment of TMD and neck mobility is
      warranted.

PMID- 16095444
TI  - Combined general-epidural anesthesia decreases the desflurane requirement for
      equivalent A-line ARX index in colorectal surgery.
AB  - BACKGROUND: The present study used the A-line ARX index, derived from auditory
      evoked potential measurements, to examine the effect of epidural lidocaine on the
      end-tidal concentration of desflurane during general anesthesia. METHODS: Thirty
      ASA I-II patients scheduled for elective colorectal surgery were included and
      randomized, in a double-blinded fashion, to receive general anesthesia, and 15 ml
      of either 2% lidocaine (group GE, n=15) or normal saline (group GS, n=15) was
      administered epidurally with a maintenance infusion rate of 6 ml h-1. After a 10
      min high-flow oxygen wash-in period, desflurane was titrated to a target A-line
      ARX index (AAI) of 20+/-5. RESULTS: Epidural lidocaine reduced the end-tidal
      concentration of desflurane required to maintain an adequate clinical effect by
      42% compared to general anesthesia alone (2.6% vs. 4.5%, respectively; P<0.001).
      The initial mean value of AAI was 87.8 (range 78-99) in group GE and 88.13 (79
      99) in group GS before general anesthesia induction, the AAI values were
      approximately 19.7 (15-25) in group GE and 20.2 (16-25) in group GS during
      anesthesia maintenance, and returned to 84.53 (77-98) in group GE and 86.87 (79
      98) in group GS when the patients regained consciousness in the recovery room. No
      statistical difference in the AAI values was observed either before, during, or
      after emergence of anesthesia. No patient reported intraoperative awareness.
      CONCLUSIONS: Lower-than-expected concentrations of volatile anesthetics are
      sufficient to maintain appropriate a clinical anesthesia effect during combined
      general-epidural anesthesia under auditory-evoked potential monitoring.

PMID- 16095445
TI  - Effects of remifentanil and alfentanil on seizure duration, stimulus amplitudes
      and recovery parameters during ECT.
AB  - BACKGROUND AND OBJECTIVE: Propofol may decrease seizure duration in
      electroconvulsive therapy. Although not proven, prolonged seizures may be more
      efficacious. The goal of this study was to evaluate and compare effects of
      alfentanil and remifentanil on seizure duration, recovery parameters and degree
      of stimulus amplitude in patients undergoing electroconvulsive therapy. METHODS:
      Twenty-four ASA I-II patients enrolled in this prospective, randomized trial,
      each receiving a total of seven electroconvulsive therapies. Patients were
      randomized to receive only Propofol, group P (0.75 mg kg-1, n=8), Propofol with
      alfentanil, group A (10 microg kg-1 alfentanil+0.5 mg kg-1 Propofol, n=8) and
      Propofol with remifentanil, group R (1 microg kg-1 remifentanil +0.5 mg kg-1
      propofol, n=8) via an iv route. Supplemental doses of propofol were given as
      required to achieve loss of consciousness. Succinylcholine 0.5 mg kg-1 iv was
      given to all groups for muscular paralysis. We recorded hemodynamic parameters,
      cortical and motor seizure durations, and recovery parameters. RESULTS: Mean
      motor seizure duration was found to be significantly longer in patients receiving
      propofol-remifentanil anesthesia (53.3+/-13.6 s) and propofol-alfentanil
      anesthesia (52.2+/-0.4 s) compared with propofol anesthesia (37.6+/-9.2 s)
      (P=0.001). Recovery parameters and stimulus amplitudes were similar in groups A
      and R; significantly different from group P (P=0.001). CONCLUSIONS: Adding 10
      microg kg-1 alfentanil or 1 microg kg-1 remifentanil to reduced doses of propofol
      provided unconsciousness and increased seizure durations. For patients who need
      higher stimulus amplitudes for longer seizure durations, combining low-dose
      propofol with alfentanil or remifentanil may be good alternative regimens for
      ECT.

PMID- 16095446
TI  - Nitrous oxide diffusion into tracheal tube cuffs--efficacy of a new prototype
      cuff pressure release valve.
AB  - BACKGROUND: The aim of this study was to evaluate the performance of a new cuff
      pressure release valve (CPRV), in which the release pressure can be adjusted from
      10 to 25 cmH2O, particularly intended to control pressure in paediatric cuffed
      tracheal tubes and to avoid cuff hyperinflation caused by N2O diffusion. METHODS:
      In vitro: the PRV was set to 10, 15, 20 or 25 cmH2O release pressure and
      connected to a cuffed tube placed into a box flushed with 66% N2O in O2. The cuff
      pressure was monitored with and without CPRV for 60 min. Experiments were
      performed four times using two different CPRVs. In vivo: with Institutional
      Review Board approval, CPRV was studied in 50 children undergoing general
      anaesthesia with tracheal intubation and standardized anaesthesia technique
      (including 66% N2O in O2) and ventilator settings. Patients were randomized into
      two groups (with and without CPRV). The cuff pressure baseline was 20 cmH2O and
      CPRV was set to 25 cmH2O. If the cuff pressure exceeded 25 cmH2O, it was manually
      released to 20 cmH2O. The numbers of deflations in both groups were noted and
      compared by Mann-Whitney U-test (P<0.05). RESULTS: In vitro: the cuff pressure
      exceeded 50 cmH2O after 60 min without CPRV, but did not exceed the settings with
      CPRV. In vivo: there was no need to manually deflate the cuff in the CPRV group
      but, in every patient in the control group, three (two to seven) deflating
      manoeuvres were required within the first hour of anaesthesia (P<0.0001).
      CONCLUSION: The CPRV allows reliable cuff pressure release at various pressure
      levels and reliably prevents cuff pressure increases caused by N2O.

PMID- 16095447
TI  - McArdle's disease and anaesthesia: case reports. Review of potential problems and
      association with malignant hyperthermia.
AB  - BACKGROUND: McArdle's disease of isolated deficiency in glycogen degradation in
      skeletal muscles has the potential of creating perioperative anaesthesiological
      problems; such as hypoglycaemia, rhabdomyolysis, myoglobinuria, acute renal
      failure and possibly malignant hyperthermia. METHODS: Eight patients with
      McArdle's disease were asked about previous surgery, anaesthesia and
      perioperative problems, and available hospital records were reviewed. Existing
      literature was reviewed for reports on McArdle's disease and anaesthesia.
      RESULTS: The eight patients had 35 anaesthesias (23 general anaesthesias, three
      regional anaesthesias and nine local anaesthesias). Perioperative problems of a
      non-specific nature were mentioned in three cases of general anaesthesia: two
      with postoperative nausea/vomiting, and one with an episode of tachycardia and
      low blood pressure. Three patients were tested for malignant hyperthermia (MH)
      using the in vitro contracture test (IVCT); two of them with a positive result.
      The literature search revealed seven case reports of McArdle's disease and
      anaesthesia. Apart from one report of hyperthermia, pulmonary oedema and
      rhabdomyolysis; probably not associated with MH, no problems were encountered
      from the literature search. CONCLUSION: McArdle's disease does not seem to cause
      severe perioperative problems in routine anaesthetic care. However, measures for
      preventing muscle ischaemia and rhabdomyolysis should be kept in mind, as well as
      the potential for these patients to develop postoperative fatigue, myoglobinuria
      and renal failure. Although no clinical association with malignant hyperthermia
      has been established, many of these patients can have a positive in vitro
      contracture test, and simple prophylactic measures, as with malignant
      hyperthermia, may be recommended if otherwise not contraindicated.

PMID- 16095448
TI  - Bispectral Index values are higher during halothane vs. sevoflurane anesthesia in
      children, but not in infants.
AB  - BACKGROUND: Previously, we have shown in adult patients that bispectral index
      score (BIS) values are significantly higher during halothane anesthesia (53-61
      units) as compared with those observed during equipotent concentrations of
      sevoflurane (39-43 units). Because halothane is frequently used in the pediatric
      setting, we tested the hypothesis that BIS values observed in children might also
      be higher during general anesthesia with halothane than with sevoflurane.
      METHODS: Forty-one healthy, unpremedicated pediatric patients scheduled for
      elective operations received either halothane or sevoflurane titrated as
      appropriate for surgical stimulation. RESULTS: During maintenance sevoflurane
      anesthesia (n=20), the mean BIS values and percent end-tidal concentrations were
      44+/-14 and 2.1+/-0.6, respectively, whereas for the halothane group (n=21) the
      corresponding values were 61+/-7 and 1.1+/-0.4, respectively. CONCLUSION: These
      findings suggest that BIS values are higher during halothane vs. sevoflurane
      anesthesia in children, but not in infants.

PMID- 16095449
TI  - Single-dose dexmedetomidine attenuates airway and circulatory reflexes during
      extubation.
AB  - BACKGROUND: The alpha agonist dexmedetomidine, a sedative and analgesic, reduces
      heart rate and blood pressure dose-dependently. We investigated whether it also
      has the ability to attenuate airway and circulatory reflexes during emergence
      from anaesthesia. METHODS: Sixty ASA I-III patients received a standard
      anaesthetic. Five minutes before the end of surgery, they were randomly allocated
      to receive either dexmedetomidine 0.5 microg/kg (Group D) (n=30) or saline
      placebo (Group P) (n=30) intravenously (i.v.) over 60 s in a double-blind design.
      The blinded anaesthetist awoke all the patients, and the number of coughs per
      patient was continuously monitored for 15 min after extubation; coughing was
      evaluated on a 4-point scale. Any laryngospasm, bronchospasm or desaturation was
      recorded. Heart rate (HR) and systolic and diastolic blood pressure (SAP, DAP)
      were measured before, during and after tracheal extubation. The time from
      tracheal extubation and emergence from anaesthesia were recorded. RESULTS: Median
      coughing scores were 1 (1-3) in Group D and 2 (1-4) in Group P (P<0.05), but
      there were no differences between the groups in the incidence of breath holding
      or desaturation. HR, SAP and DAP increased at extubation in both groups (P<0.05),
      but the increase was less significant with dexmedetomidine. The time from
      tracheal extubation and emergence from anaesthesia were similar in both groups.
      CONCLUSION: These findings suggest that a single-dose bolus injection of
      dexmedetomidine before tracheal extubation attenuates airway-circulatory reflexes
      during extubation.

PMID- 16095450
TI  - Ethical issues in intensive care--a survey among Scandinavian intensivists.
AB  - BACKGROUND: The general principles of medical ethics are universally accepted. In
      practice, however, there is variation on how these principles are interpreted by
      people with different cultural backgrounds. The aim of this study was to document
      the views of Scandinavian intensive care physicians on intensive care unit (ICU)
      admission, triage, withholding and withdrawal of intensive care, and
      communication between the patient, the family and the ICU team. METHODS: A
      questionnaire was developed and sent to 84 intensive care physicians working in
      Denmark, Finland, Sweden and Norway. RESULTS: The response rate was 61%. In
      general, the responses were in agreement with published guidelines. Nevertheless,
      there was considerable variation on what factors are taken into account when
      priority decisions are made. In addition, the views on the content of information
      provided to the family varied. A majority of 80% reported priority decisions
      being made on a regular basis. Less than one-half of the respondents had correct
      knowledge regarding the existence or lack of national guidelines on intensive
      care ethics. Only 8% of the respondents were aware of guidelines published by the
      Society of Critical Care Medicine. CONCLUSION: Variation in priority determinants
      between individual physicians may compromise justice in health care. An effort
      should be made to discuss and adopt mutual principles. In addition, the quality
      of information available to the patients' representatives deserves our attention.
      The results of this study could be used as a basis for discussion when guidelines
      on the ethical aspects of intensive care are developed and reviewed.

PMID- 16095451
TI  - Effect of prolonged mechanical ventilation on diaphragm muscle mitochondria in
      piglets.
AB  - BACKGROUND: Respiratory muscle weakness is a common problem in the intensive care
      unit and could be involved in difficulties in weaning from the ventilator after
      prolonged mechanical ventilation. Animal models have shown that mechanical
      ventilation itself impairs diaphragm muscle function. In this study we
      investigated whether diaphragm contractile impairment caused by mechanical
      ventilation and immobilization in piglets is associated with a derangement in
      diaphragm mitochondria. METHODS: Seven piglets received controlled mechanical
      ventilation during 5 days. A control group of eight piglets were anaesthetized
      and surgically manipulated in the same way, but were mechanically ventilated for
      4-6 h. After mechanical ventilation, diaphragm muscle biopsies were taken for
      measurements of mitochondria content, mitochondrial respiratory enzymes and
      markers of oxidative stress. RESULTS: Diaphragm mitochondrial content, as
      assessed by citrate synthase activities and volume density, was not different
      between the control and ventilated piglets. Activity of complex IV of the
      mitochondrial respiratory chain decreased by 21% (P=0.02) when expressed per
      muscle weight and by 11% (P=0.03) when expressed per citrate synthase activity.
      There were no changes in the markers of oxidative stress between the two groups.
      CONCLUSION: Five days of mechanical ventilation and immobilization decreased the
      activity of complex IV of the mitochondrial respiratory chain in the diaphragm
      muscle of the piglets.

PMID- 16095452
TI  - Glycine--an important neurotransmitter and cytoprotective agent.
AB  - BACKGROUND: Glycine, the simplest of the amino acids, is an essential component
      of important biological molecules, a key substance in many metabolic reactions,
      the major inhibitory neurotransmitter in the spinal cord and brain stem, and an
      anti-inflammatory, cytoprotective, and immune modulating substance. MATERIAL AND
      METHODS: Based on available literature, we discuss some of the important
      biological properties of glycine. In addition, we describe some clinical
      disorders where glycine plays a central role, either as an essential structural
      element, or through its metabolism or receptors. RESULTS: The past few years have
      witnessed a broadening of glycine research. The traditional prime interest in
      aspects related to its role as an inhibitory neurotransmitter in the central
      nervous system has been expanded to equally emphasize other organs and tissues.
      With the demonstration of glycine-gated chloride channels on neurons in the
      central nervous system, on most leukocytes, and subsequently on other cells as
      well, a unifying mechanism of action accounting for many of the widespread
      effects of glycine has been found. CONCLUSIONS: Glycine is a simple, easily
      available, and inexpensive substance with few and innocuous side-effects. The
      diversity of biological activities is well documented in the literature. Despite
      this, glycine has only gained a modest place in clinical medicine.

PMID- 16095453
TI  - Neuroprotective effect of mivazerol, an alpha 2-agonist, after transient
      forebrain ischemia in rats.
AB  - BACKGROUND: We examined whether mivazerol, an alpha2-agonist, had neuroprotective
      effects after transient forebrain ischemia in rats. METHODS: Male Sprague-Dawley
      rats, anesthetized with halothane, were assigned to one of four groups (n=10
      each): control (C, normal saline) and mivazerol 10 microg/kg (M10), 20 microg/kg
      (M20) and 40 microg/kg (M40) groups. Thirty minutes after drug administration,
      forebrain ischemia was induced with hemorrhagic hypotension and bilateral carotid
      artery occlusion for 10 min, and then the brain was reperfused. The neurologic
      outcome was evaluated 24 h, 48 h and 7 days after ischemia, followed by
      histologic evaluation. RESULTS: The survival rate during 7 days was significantly
      lower in group M40 than in groups M10 and M20 (P<0.05). The neurologic outcome
      was significantly better in groups M10 and M20 than in group M40 7 days after
      ischemia (P<0.05). The number of intact neurons in hippocampal CA1 was
      significantly greater in group M20 than in the other groups (P<0.05). Neuronal
      injury in the neocortex was significantly less in group M20 than in groups C and
      M40 (P<0.05). CONCLUSIONS: Our results suggest that mivazerol, up to 20
      microg/kg, provides neuroprotective effects, whereas 40 microg/kg may exaggerate
      neuronal injury after transient forebrain ischemia in rats.

PMID- 16095454
TI  - Beneficial effects of hypertonic saline/dextran on early survival in porcine
      endotoxin shock.
AB  - BACKGROUND: Hypertonic saline/dextran (HSD) has been shown to have beneficial
      effects in haemorrhagic shock. These effects, with improved haemodynamics and
      organ perfusion, would in theory also be of benefit in septic shock. However,
      this is less studied. We have therefore further evaluated the effect of
      additional treatment with HSD in a porcine endotoxin shock model. METHODS:
      Sixteen anaesthetized pigs were used. A continuous infusion of endotoxin (LPS EC)
      was increased stepwise during 30 min to a rate of 5 microg/kg/h. The infusion was
      discontinued after 3 h and the animals were observed for another 2 h. The animals
      received continuous basal fluid resuscitation with isotonic Ringer's glucose 2.5%
      at a rate of 20 ml/kg/h throughout the experiment. After 1 h of endotoxin
      infusion, the animals were randomized to additional treatment with HSD, 4 ml/kg
      over 5 min, or the same volume of isotonic saline. Every 30 min, haemodynamics
      and mixed venous saturation (SvO2) were measured via a pulmonary artery catheter.
      Regional blood flow rates were measured continuously by perivascular ultrasonic
      flow probes. The metabolic response was measured by arterial blood gas analysis.
      RESULTS: The endotoxin put all animals into a progressive hypodynamic circulatory
      shock during the experiment. Treatment with HSD improved survival rate to 8/8
      compared with controls 3/8. There was a transient circulatory recovery with
      improved central and regional haemodynamics, accompanied by stabilized metabolic
      response. CONCLUSION: Treatment with additional HSD improves survival in an early
      phase of endotoxin shock. Generally improved haemodynamics and oxygenation of
      peripheral tissues are suggested as possible mechanisms.

PMID- 16095455
TI  - Effective systolic orifice area of the aortic valve: implications for Doppler
      echocardiographic cardiac output determinations.
AB  - BACKGROUND: Substantial research using echocardiography has established that
      stroke volume (SV) or cardiac output (CO) can be measured non-invasively at the
      level of the aortic valve (AV) with high accuracy. Stroke volume is the product
      of the velocity time integral occurring at the sampling site and the effective
      systolic AV orifice area (AVOAeff). Nevertheless, a generally accepted method for
      the determination of AVOAeff is still lacking. METHODS: Aortic valve OAeff was
      measured in 228 consecutive patients scheduled for coronary artery surgery. Two
      widely adopted methods were applied to approximate the constantly changing
      orifice area of the AV: (1) the circular orifice model (AVOA-CM), and (2) the
      triangular orifice model (AVOA-TM). Aortic valve OA-CM assumes the shape of a
      circle as an appropriately time averaged geometrical model, and AVOA-TM takes the
      shape of an equilateral triangle for granted. RESULTS: The AV was easily imaged
      by echocardiography in both short- and long-axis views in all patients. Relying
      on AVOA-CM, AVOAeff was 3.49+/-0.77 cm2. AVOA-TM estimates were 2.80+/-0.55 cm2
      (mean+/-SD). The results did not agree (bias analysis). CONCLUSIONS: The
      echocardiographic measurement of SV or CO at the level of the AV has to be
      reconsidered.

PMID- 16095456
TI  - Antithrombin III pretreatment reduces neutrophil recruitment into the lung and
      skeletal muscle tissues in the rat model of bilateral lower limb ischemia and
      reperfusion: a pilot study.
AB  - BACKGROUND: Anti-inflammatory action of Antithrombin III (AT III) is still not
      well understood in ischemia/reperfusion (I/R) injury. In the present study, we
      aimed to investigate the anti-inflammatory action of AT III on remote lung and
      local skeletal muscle tissue injury in a rat model of bilateral lower limb I/R
      model. METHODS: Bilateral lower limb ischemia and reperfusion were produced by
      means of tourniquets occlusions and releases, respectively. Three groups of rats
      were used in this controlled study: sham group (sham, n=3) underwent 5 h of
      anesthesia only; control group (I/R, n=7) underwent 3 h of bilateral lower limb
      ischemia followed by 2 h of reperfusion; and AT III pretreated group (I/R-AT III,
      n=6) underwent the same procedure as the control group, but also received i.v.
      250 U kg-1 AT III 30 min before ischemia induction under midazolam and fentanyl
      anesthesia. MEASUREMENTS AND RESULTS: Lung and muscle tissue accumulation of
      polymorphonuclear leukocytes (PMN) were assessed by measuring tissue
      myeloperoxidase (MPO) activity. Histopathological changes in tissues were
      assessed by PMN counts in the lung, and muscle tissues and by histological lung
      injury score. Plasma 6-keto prostaglandin F(1alpha) and tumor necrosis factor
      alpha levels were measured by an enzyme immunoassay technique. Myeloperoxidase
      activity could not be detected in the muscle tissues of all groups. The lung and
      muscle tissue PMN counts in the I/R group were significantly higher compared with
      the I/R-AT III group (P<0.05). CONCLUSIONS: Data from the present study provides
      some evidence that AT III pretreatment attenuates remote lung and local skeletal
      muscle tissue injury caused by lower limb I/R.

PMID- 16095457
TI  - Venous oxygen saturation during normovolaemic haemodilution in the pig.
AB  - BACKGROUND: Hypovolaemia may be considered to represent a volume-restricted
      cardiac output (CO), but CO varies inversely with the haemoglobin concentration
      (Hb) and a maximal mixed venous oxygen saturation (SvO2) may be a better target
      for volume administration than a maximal CO. METHODS: In 10 anaesthetized pigs,
      volume loading with 6% hydroxyethyl starch was performed to obtain a maximal SvO2
      followed by normovolaemic haemodilution with 6% hydroxyethyl starch. RESULTS:
      Volume loading increased SvO2 from 55.0+/-5.2% to 64.8+/-9.0% (mean+/-SD)
      associated with an increase in CO (2.3+/-0.4 to 3.5+/-0.9 l/min) and central
      venous oxygen saturation (ScvO2; 68.2+/-9.3% to 79.4+/-7.2%; P<0.05). Heart rate
      (HR), mean arterial (MAP), central venous (CVP), pulmonary arterial mean (PAMP),
      and occlusion pressures (PAOP) increased as well (P<0.05). In contrast, during
      progressive haemodilution, SvO2 and ScvO2 remained statistically unchanged until
      the haemoglobin concentration had decreased from 5.5+/-0.4 to 2.9+/-0.2 mM, while
      CO and HR increased at a haemoglobin value of 4.4+/-0.4 and 4.0+/-0.4 mM and CVP
      and PAOP decreased at a haemoglobin of 4.0+/-0.4 and 2.9+/-0.2 mM, respectively
      (P<0.05) leaving MAP unaffected. CONCLUSION: This study found that volume loading
      increased cardiac output and mixed and central venous oxygen saturations in
      parallel, but during normovolaemic haemodilution an increase in cardiac output
      left mixed and central venous oxygen saturations statistically unchanged until
      haemoglobin concentration was reduced by approximately 50%. Accordingly, volume
      therapy should be directed to maintain a high venous oxygen saturation rather
      than a change in cardiac output.

PMID- 16095458
TI  - Respiration can be monitored by photoplethysmography with high sensitivity and
      specificity regardless of anaesthesia and ventilatory mode.
AB  - BACKGROUND: Photoplethysmography (PPG) is a non-invasive optical technique used,
      for instance, in pulse oximetry. Beside the pulse synchronous component, PPG has
      a respiratory synchronous variation (PPGr). Efforts have been made to utilize
      this component for indirect monitoring of respiratory rate and volume. Assessment
      of the clinical usefulness as well as of the physiological background of PPGr is
      required. We evaluated if anaesthesia and positive-pressure ventilation would
      affect PPGr. METHODS: We recorded reflection mode PPGr, at the forearm, and the
      respiratory synchronous changes in central venous pressure (CVP), peripheral
      venous pressure (PVP) and arterial blood pressure (ABP) in 12 patients.
      Recordings for each patient were made on three occasions: awake with spontaneous
      breathing; anaesthetized with spontaneous breathing; and anaesthetized with
      positive-pressure ventilation. We analyzed the sensitivity, specificity,
      coherence and time relationship between the signals. RESULTS: PPGr sensitivity
      for breath detection was [mean (SD)] >86(21)% and specificity >96(12)%.
      Respiratory detection in the macrocirculation (CVP, PVP and ABP) showed a
      sensitivity >83(29)% and specificity >93(12)%. The coherence between signals was
      high (0.75-0.99). The three measurement situations did not significantly
      influence sensitivity, specificity or time shifts between the PPGr, PVP, ABP, and
      the reference CVP signal despite changes in physiological data between
      measurements. CONCLUSION: A respiratory synchronous variation in PPG and all
      invasive pressure signals was detected. The reflection mode PPGr signal seemed to
      be a constant phenomenon related to respiration regardless of whether or not the
      subject was awake, anaesthetized or ventilated, which increases its clinical
      usefulness in respiratory monitoring.

PMID- 16095459
TI  - Colloids decrease clot propagation and strength: role of factor XIII-fibrin
      polymer and thrombin-fibrinogen interactions.
AB  - Colloid-mediated hypocoagulability is clinically important, but the mechanisms
      responsible for coagulopathy have been incompletely defined. Thus, my goal was to
      elucidate how colloids decrease plasma coagulation function. Plasma was diluted
      0% or 40% with 0.9% NaCl, three different hydroxyethyl starches (HES, mean
      molecular weight 450, 220 or 130 kDa), or 5% human albumin. Samples (n=6 per
      condition) were activated with celite, and diluted samples had either no
      additions or addition of fibrinogen (FI), thrombin (FIIa) or activated Factor
      XIII (FXIIIa) to restore protein function to prediluted values.
      Thrombelastographic variables measured included clot propagation (angle, alpha),
      and clot strength (amplitude, A; or shear elastic modulus, G). Dilution with 0.9%
      NaCl significantly decreased alpha, A and G-values compared to undiluted samples.
      Supplementation with FI, but not FIIa or FXIIIa, resulted in 0.9% NaCl-diluted
      thrombelastographic variable values not different from those of undiluted
      samples. FI supplementation of HES 450, HES 220, HES 130 and albumin-diluted
      samples only partially restored alpha, A and G-values compared to undiluted
      samples. FIIa addition only improved clot propagation and strength in albumin
      diluted samples. FXIIIa supplementation improved propagation in samples diluted
      with HES 450, HES 220 and albumin, and clot strength improved in HES 450 and
      albumin-diluted plasma. Considered as a whole, these data support compromise of
      FIIa-FI and FXIIIa--fibrin polymer interactions as the mechanisms by which
      colloids compromise plasma coagulation. Investigation to determine if clinical
      enhancement of FXIII activity and/or FI concentration (e.g. fresh-frozen plasma,
      cryoprecipitate) can attenuate colloid-mediated decreases in hemostasis is
      warranted.

PMID- 16095460
TI  - Retrograde cerebral perfusion of oxygenated, compacted red blood cells attenuates
      brain damage after hypothermia circulation arrest of rat.
AB  - BACKGROUND: It was proved that higher haematocrit (Hct) might improve the
      function of brain after hypothermia circulation arrest (HCA). In the present
      study we established a new rat HCA model and investigated whether retrograde
      cerebral perfusion of oxygenated, compacted red blood cells (RBC) could attenuate
      brain injury after HCA. METHODS: A new rat HCA model was developed and rats were
      randomly distributed into three groups: HCA group, HCA combined with retrograde
      cerebral perfusion of oxygenated, compacted red blood cell group (HCArcp group),
      and sham operation group (sham op. group). Animals both in the HCA group and in
      the HCArcp group underwent HCA 90 min at 18 degrees C. Brain damage after HCA was
      evaluated with light microscopy and electron microscopy. Immunohistochemistry and
      RT-PCR techniques were used to measured the different expressions of the C-Fos,
      Bcl-2, Bax mRNA and protein among the groups. Additionally we measured the
      wet/dry ratio of the brain in order to evaluate the oedema degree after HCA.
      RESULTS: The new HCA model of rat we developed was comparable to the clinical
      setting not only in terms of the intubation, anaesthesia method and materials
      employed but also in terms of the priming volume in relation to body weight. The
      number of injured neurones in the hippocampus CA1 and parietal cortex, but not in
      the thalamus of the HCA group, was significantly greater than that of the HCArcp
      group (P<0.05). The mean score of mitochondrion of the hippocampus CA1 in the HCA
      group was significantly higher than in the HCArcp group (P<0.05). The expression
      of C-Fos, Bax mRNA and protein in the hippocampus CA1 and/or parietal cortex area
      was higher in the HCA group than in the HCArcp group (P<0.05). Expression of the
      mRNA and protein of Bcl-2 was higher in the HCArcp group than in the HCA group
      (P<0.05). The degree of oedema after HCA between the HCA group and HCArcp group
      had no significant difference (P>0.05). CONCLUSIONS: We established a new rat
      model of HCA comparable to the clinical setting. Retrograde cerebral perfusion of
      oxygenated, compacted RBC is a simple, effective, and safe method to protect the
      brain during HCA. Adjusting the gene expression in relation to apoptosis might
      contribute to the neuroprotective effects of a retrograde cerebral infusion of
      oxygenated, compacted RBC.

PMID- 16095461
TI  - Impact of postoperative shed blood transfusion, with or without leucocyte
      reduction, on acute-phase response to surgery for total knee replacement.
AB  - BACKGROUND: In patients undergoing total knee replacement (TKR) most blood loss
      occurs postoperatively and return of unwashed filtered shed blood (USB) from
      postoperative drainage may represent an alternative to allogeneic blood
      transfusion (ABT). We evaluated the impact of USB return, with or without
      leucocytes, on the acute-phase response (APR) after TKR. PATIENTS AND METHODS:
      Forty-eight TKR patients, intended to receive postoperative USB, entered the
      study. Blood samples were obtained before and 6, 24, 72 h and 7 days after
      surgery, and from the USB before and after it passed through a 40-microm filter
      (Group F40) or a leucocyte-reduction filter (Group LRF). Haematimetric
      parameters, APR proteins (albumin, prealbumin, ceruloplasmin, haptoglobin, C
      reactive protein), complement C3 and C4, and cytokines (IL-1beta, IL-6, IL-8, IL
      10, and TNF-alpha) were measured in all samples. RESULTS: Twenty-eight patients
      (Group F40=14, Group LRF=14) received a mean of 1.2 USB units, without any
      clinically relevant incident, and did not need additional ABT. Sixteen out of the
      20 remaining patients who received neither USB nor ABT served as a control group
      for the postoperative APR study. All patients showed the typical postoperative
      APR profile and there were no significant differences between groups for APR
      parameters, postoperative complications, or hospital stay. CONCLUSIONS:
      Postoperative blood salvage and return, with or without a LRF, after TKR does not
      present any clinically relevant side-effects and does not modify APR induced by
      surgery. These findings seem to confirm the clinical experience that
      postoperative USB return is safe and questions the beneficial effect of using
      LRF.

PMID- 16095462
TI  - Postoperative extradural analgesia with morphine and ropivacaine. A double-blind
      comparison between placebo and ropivacaine 10 mg/h or 16 mg/h.
AB  - BACKGROUND: Some controversy exists in the literature on the benefit of epidurals
      compared to patient-controlled intravenous analgesia (PCA). Also, the dose of
      ropivacaine for epidural analgesia when combined with morphine remains uncertain.
      The aim of this study was to compare the epidural vs. PCA technique and high-dose
      vs. low-dose ropivacaine combined with morphine during knee replacement surgery.
      METHODS: In this prospective, randomized, double-blind study, postoperative pain
      relief with a combination of epidural ropivacaine (Group L: 10 mg h-1, Group H:
      16 mg h-1) and morphine (0.16 mg h-1) was evaluated in 30 patients. A placebo
      group (Group PL) of 15 patients having PCA morphine served as the control. Visual
      analog pain (VAS), morphine consumption, sensory and motor block and side-effects
      were recorded during 48 h. RESULTS: VAS scores at rest were significantly lower
      in Groups L and H compared to Group PL. On movement, Group H had lower VAS scores
      than Group PL during 3-27 h (P<0.05) and Group L during 4-9 h (P<0.05), while
      Group L had lower a VAS than Group PL during 9-18 h (P<0.05). Morphine
      consumption after 48 h was greater in Group PL (64.6+/-36.3 mg) vs. Group L
      (23.3+/-33.9 mg) (P<0.001) and Group H (4.3+/-9.6 mg) (P<0.0001). Mild motor
      block was seen in Group H in 20% and 14% patients at 24 h and 48 h, respectively,
      but time to mobilization was similar between the groups. Pruritus was more common
      in the ropivacaine groups (P<0.05). CONCLUSION: Lumbar epidural analgesia using a
      combination of ropivacaine (16 mg h-1) and morphine (0.16 mg h-1) provides
      superior analgesia compared to the PCA technique or ropivacaine (10 mg h-1) and
      morphine (0.16 mg h-1). Although this resulted in a mild motor block during the
      first 12 h, patient mobilization was similar in all groups.

PMID- 16095463
TI  - Colloid vs. crystalloid preloading to prevent maternal hypotension during spinal
      anesthesia for elective cesarean section.
AB  - BACKGROUND: Hypotension associated with spinal anesthesia for cesarean section is
      still a clinical problem. Colloid solutions seem preferable to crystalloid
      solutions for preloading. In most studies the overall rate of hypotension is
      reported. Few studies have, however, investigated the maternal and neonatal
      consequences of different levels of maternal hypotension. METHODS: In this
      randomized, double-blinded study 110 patients presenting for elective cesarean
      section received either 1000 ml acetated Ringer's solution or 1000 ml 3% dextran
      60 solution immediately before spinal anesthesia. The effect on overall
      hypotension, clinically significant hypotension (hypotension associated with
      maternal discomfort defined as nausea, retching/vomiting, dizziness or chest
      symptoms) and severe hypotension (systolic arterial pressure <80 mmHg) was
      studied. RESULTS: Dextran reduced the incidence of overall hypotension from 85 to
      66% (P=0.03), reduced the incidence of clinically significant hypotension from 60
      to 30% (P=0.002) and reduced the incidence of severe hypotension from 23 to 3.6%
      (P=0.004) compared to Ringer's solution. There were neither differences in
      neonatal outcome between treatment groups nor between neonates grouped after
      severity of maternal hypotension. CONCLUSION: Clinically significant hypotension
      seems to be a more suitable outcome variable than overall hypotension. The
      protective effect of the colloid solution increased with increased severity of
      hypotension.

PMID- 16095464
TI  - Bradycardia and hypertension in anticipation of, and exacerbated by, peribulbar
      block: a prospective audit.
AB  - BACKGROUND: Changes in heart rate (HR), systolic arterial pressure (SAP) and
      diastolic arterial pressure (DAP) occur in anticipation of, and following,
      injection of a peribulbar local analgesic agent. We examined these changes in two
      groups of awake patients given a pre-medication of either hydroxyzine 1.0 mg/kg
      alone (control) or hydroxyzine 1.0 mg/kg with morphine 0.05 mg/kg. METHODS: HR,
      SAP and DAP of 100 patients per group were monitored the day before surgery
      (baseline), every 5 min in the anesthesia holding room before peribulbar
      injection, every minute for the first 5 min after peribulbar injection and then
      every 5 min until transfer to the operating room. Within and between pre
      medication group values of HR, SAP and DAP before and after peribulbar injection
      were compared with baseline. RESULTS: The two groups of patients were similar.
      Before peribulbar injection, HR was unchanged in the hydroxyzine group, but 6%
      slower in those given morphine (P<0.01). After injection, HR slowed in both
      groups, by 5% and 7% (P<0.01, both comparisons), respectively. In anticipation of
      injection, SAP increased in both groups to 20% and 16% above baseline,
      respectively, and increased further after injection to 26% and 24% above
      baseline, respectively (P<0.001, all comparisons). In both groups, maximum SAP
      following injection exceeded maximum SAP before injection (P<0.02, both
      comparisons). DAP increased by 4% (P<0.05) in the hydroxyzine group before
      injection, and by 5% and 4%, respectively (P<0.005 and P<0.05, respectively)
      after peribulbar injection. CONCLUSION: The audit reveals pronounced increases in
      SAP accompanied by lesser increases in DAP and a tendency to slowing of HR in
      awake patients in anticipation of peribulbar injections. Peribulbar injections
      cause further increases in blood pressure and mild bradycardia. These changes
      occur similarly in patients pre-medicated with hydroxyzine or hydroxyzine plus
      morphine. A mix of neuro-humoral influences
      (anxiety/catecholamine/baroreceptor/trigemino-vagal) are postulated as
      etiological.

PMID- 16095465
TI  - Ventilatory management and weaning in a patient with central hypoventilation
      caused by a brainstem cavernoma.
AB  - We describe a patient with a brainstem cavernoma who was dependent on hypoxic
      respiratory drive initially. After excision of the lesion, the patient developed
      severe hypoventilation unresponsive to both hypoxia and hypercapnia. Weaning from
      mechanical ventilation could be achieved through central respiratory stimulation
      by acetazolamide. Problems associated with respiratory management of central
      hypoventilation due to a brainstem lesion are described.

PMID- 16095466
TI  - Tracheal intubation using a new CCD camera-equipped device: a report of two cases
      with a difficult intubation.
AB  - In two patients, one with Klippel-Feil syndrome and one with fibrous dysplasia of
      the maxilla, no part of the larynx could be visualized by direct laryngoscopy. In
      both cases, the use of an intubation device equipped with a charge-coupled device
      camera, the endotracheal intubation device (EID), allowed smooth tracheal
      intubation.

PMID- 16095467
TI  - No change in vital signs or CBF at 1 MAC sevoflurane?

PMID- 16095468
TI  - Sevoflurane and CBF: there is much more out there than you might expect.

PMID- 16095469
TI  - Peer review--still the well-functioning quality control and enhancer in
      scientific research.

PMID- 16095470
TI  - Suicides and suicide ideation in the Bible: an empirical survey.
AB  - OBJECTIVE: The aim of this review is to summarize all data on suicidal behaviour
      reported in the Bible and to discuss basic implications for medical ethical
      positions. METHOD: All books of the Jerusalem Bible, including the apocrypha
      accepted in the Catholic canon, were searched for all cases of suicide, attempted
      suicide and suicidal ideation clearly identifiable as such. RESULTS: The Bible
      including the apocrypha reports about 10 completed suicides and 11 cases of
      suicide attempt or ideation. The Bible considers human life as a divine gift but
      suicide per se is neither condemned nor approved. Those suffering from suicidal
      thoughts are treated with respect and support is offered. CONCLUSION: Theological
      teaching on suicide was influenced for centuries by the biased negative opinion
      of the early fathers of the church and scholastic savants, but these opinions are
      not substantiated by a thorough reading of the Bible.

PMID- 16095471
TI  - A randomized comparison of group cognitive-behavioural therapy and group
      psychoeducation in acute patients with schizophrenia: outcome at 24 months.
AB  - OBJECTIVE: We compared the effects of a brief group cognitive-behavioural therapy
      (CBT) and a group psychoeducational (PE) programme in acute patients with
      schizophrenia 2 years after treatment. At 6-month follow-up, the CBT group had
      shown significantly less re-hospitalization rates and on a descriptive level
      higher compliance with medication. METHOD: Eighty-eight in-patients with acute
      schizophrenia were randomized to receive a therapy envelope of 8 weeks including
      either 16 sessions of CBT or eight sessions of PE. RESULTS: From the initial
      sample, 43 patients (48.9%) completed the 24-month follow-up. There were no
      significant group differences regarding re-admission, symptoms or compliance with
      medication. However, on a descriptive level patients who received CBT on average
      experienced 21.8% less re-hospitalizations, 71 days less in hospital and higher
      compliance ratings at the 24-month follow-up. CONCLUSION: The significant
      advantages of CBT at short-term follow-up were lost at long-term follow-up.
      However, on a descriptive level some advantages for CBT remained after 2 years.

PMID- 16095472
TI  - Cognitive-behavioral group therapy for obsessive-compulsive disorder: a 1-year
      follow-up.
AB  - OBJECTIVE: The aim of this study was to evaluate the results of cognitive
      behavioral group therapy (CBGT) for obsessive-compulsive disorder (OCD) over a 1
      year follow-up period. METHOD: Forty-two OCD patients, who completed 12 sessions
      of CBGT, were followed for 1 year. Measures of the severity of symptoms were
      obtained at the end of the acute treatment and at 3, 6, and 12 months post
      treatment using the Yale-Brown obsessive-compulsive scale (Y-BOCS) and the
      clinical global impression (CGI). RESULTS: The reduction in the severity of
      symptoms observed at the end of the treatment was maintained during 1 year
      (F2,41=1.1; P=0.342). Eleven patients (35.5%) relapsed in the follow-up period.
      The intensity of improvement (log rank=12.97, GL=1, P=0.0003) and full remission
      (log rank=6.17; GL=1; P=0.001) were strong predictors for non-relapsing.
      CONCLUSION: The CBGT is an effective treatment for OCD and its results are
      maintained for 1 year. However, further long-term randomized controlled trials
      are needed in order to confirm this finding.

PMID- 16095473
TI  - Cognitive training of verbal memory using a dichotic listening paradigm: impact
      on symptoms and cognition.
AB  - OBJECTIVE: The objective was to investigate the impact of a verbal memory
      training task on psychiatric symptoms and cognition in schizophrenia. METHOD: As
      part of a larger, 6-month cognitive remediation program, 57 patients with
      schizophrenia were randomly assigned to receive performance-based, hierarchical
      training on a verbal memory task based on a dichotic listening (DL) with
      distracter paradigm. These patients were compared with 68 patients who had been
      randomly assigned to a control condition. RESULTS: Training on the DL task was
      not associated with changes in general psychopathology or auditory hallucinations
      (AH) specifically. Training was associated with improvements in verbal memory,
      but not attention. CONCLUSION: The current investigation adds to the growing
      literature on the effectiveness of cognitive remediation training and indicates
      that training on the DL task enhances verbal episodic memory. The results do not
      support the use of DL training as a method for reducing AH.

PMID- 16095474
TI  - Psychological aftermath of the Lviv air show disaster: a prospective controlled
      study.
AB  - OBJECTIVE: To investigate the psychological aftermath of an air show disaster
      using prospectively obtained epidemiologic data. METHOD: Participants in a
      recently completed epidemiologic mental health survey in Lviv (disaster site) and
      controls from western Ukraine were interviewed shortly before and 6 months after
      a gruesome air show disaster. RESULTS: The Lviv group reported more
      psychopathology and post-traumatic stress symptom severity, but less anomie than
      controls. Somatization symptoms were similar in the two groups. Predisaster
      mental health and postdisaster threat were the strongest risk factors while
      demographic characteristics, emotional support, and repeated television viewing
      of the event were only weakly associated with postdisaster mental health.
      CONCLUSION: This is the first prospective study to find a significantly higher
      rate of disorder as well as post-traumatic stress disorder symptomatology after a
      disaster. The risk factor findings suggest avenues for targeting postdisaster
      interventions.

PMID- 16095475
TI  - Neuropsychiatric disturbances in Parkinson's disease clusters in five groups with
      different prevalence of dementia.
AB  - OBJECTIVE: To investigate the inter-relationship of neuropsychiatric disturbances
      in Parkinson's disease (PD) by cluster analysis and describe the properties of
      the clusters. METHOD: A total of 139 patients were assessed using the
      neuropsychiatric inventory (NPI). A cluster-analysis was used to investigate the
      inter-relationship of NPI items. The clusters were profiled regarding dementia
      (PDD) and major depression. RESULTS: A total of 39 patients showed no
      neuropsychiatric symptoms. The remaining 100 patients (43% PDD) were divided in
      to five clusters. The largest group (42, 31% PDD) showed symptoms of mild
      depression, followed by a group (29, 79.3% PDD) with hallucinations and mild
      other symptoms. The third group (14, 7.1% PDD) had sleep disturbances
      exclusively. The fourth group (8, 25% PDD) showed apathy, anxiety and depression.
      The smallest group (7, 57.1% PDD) had high scores on several NPI items.
      CONCLUSION: Our PD sample can be divided in to clusters based on the NPI, with
      different prevalence of dementia and depression.

PMID- 16095476
TI  - Avoidant personality disorder and social phobia: distinct enough to be separate
      disorders?
AB  - OBJECTIVE: Existing evidence from anxiety disorder research indicates that social
      phobics (SP) with avoidant personality disorder (AVPD) experience more anxiety
      and show more impairment than patients with SP alone. The purpose of this study
      was to examine whether in patients diagnosed with AVPD, the co-occurrence of SP
      adds to its severity. We hypothesized that the addition of SP will not add to the
      severity of AVPD alone. METHOD: Two groups of patients (AVPD=224; AVPD/SP=101)
      were compared at baseline and 2 years later on multiple demographic and clinical
      variables. RESULTS: Patients with AVPD and an additional diagnosis of SP differed
      little from patients with AVPD alone. CONCLUSION: These findings suggest that
      AVPD and SP may be alternative conceptualizations of the same disorder.

PMID- 16095477
TI  - Does socioeconomic status affect the use of community-based psychiatric services?
      A South Verona case register study.
AB  - OBJECTIVE: To assess the effect of socioeconomic status (SES) on psychiatric
      service use in an Italian area with a well-developed community-based psychiatric
      service. METHOD: An index of SES was calculated from nine census variables and
      grouped into four categories, ranging from SES-I-affluent to SES-IV-deprived, for
      each of 328 census blocks (CB). Fifteen indicators of psychiatric service use
      were collected using the psychiatric case register. All patients resident in the
      catchment area, who had at least one psychiatric contact in 1996 (n=989), were
      included in the study. RESULTS: Indicators of in-patient, day-patient, out
      patient and community service use showed an inverse association with SES. Only
      first-ever and long-term psychotic patients were equally distributed in the four
      SES groups. CONCLUSION: The inverse association between SES and most indicators
      of psychiatric service use suggests that the planning of community-based services
      and resource allocation should take into account the SES of residents.

PMID- 16095478
TI  - The Nottingham study of neurotic disorder: predictors of 12 year costs.
AB  - OBJECTIVE: To examine the relationship between clinical, demographic and socio
      economic characteristics and the long-term costs of a cohort of neurotic
      patients. METHOD: Analysis of the costs of a cohort of 210 people entered in the
      Nottingham study of neurotic disorders, a randomized controlled evaluation of
      five treatments for neurotic disorders. Service use data were collected at 5 and
      12 years after study entry. Multiple regression analyses were conducted. RESULTS:
      The total cost per patient over the 12-year follow-up period was calculated to be
      $11,940 (SD $15,520) ( pound7450, SD pound9690). Higher costs were significantly
      associated with the presence of general neurotic syndrome, an initial diagnosis
      of dysthymia and a recurrent episode of illness. CONCLUSION: The total costs of
      care for a range of neurotic disorders are broadly comparable with other
      estimates of costs reported in the literature for similar populations. Those
      responsible for higher costs in the longer-term have comorbid anxiety, depressive
      and personality disorders.

PMID- 16095479
TI  - Postpartum depression without delivering a child?
AB  - OBJECTIVE: Depression in people related to delivering women is documented in
      their mates, but only anecdotal in other family members. We describe a case of
      depression in a woman who had previously experienced postpartum depression after
      the birth of her nephew. METHOD: A clinical description of the case. RESULTS: A
      53-year-old woman, hysterectomized at age 47 years, was admitted for attempted
      suicide. She developed major depressive episode 1 month after her daughter had
      delivered a son. She had a past history of two postpartum depressive episodes
      clinically identical to the current episode. The episode resolved after 5 weeks.
      At 1-year follow-up, the patient is still asymptomatic. CONCLUSION: Psychological
      and cultural factors were at play in this case more than hormonal and
      biopsychosocial ones.

PMID- 16095481
TI  - Atypical neuroleptic malignant syndrome caused by olanzapine.
AB  - OBJECTIVE: Neuroleptic malignant syndrome (NMS) is a rare syndrome with four main
      symptoms: rigidity, hyperthermia, altered mental status and autonomic
      instability. We report a patient with an atypical manifestation of NMS. METHOD: A
      single case was reported. RESULTS: A patient with pneumonia developed delirium
      and was treated with olanzapine and developed a NMS with fluctuating hyperthermia
      and autonomic instability during a month. Only slight rigidity was present.
      Creatine kinase was not elevated. The patient was severely agitated and manic.
      After discontinuation of olanzapine the patient showed no psychopathology or
      hyperthermia. CONCLUSION: NMS should be considered when patients treated with
      antipsychotics develop one or more symptoms of NMS.

PMID- 16095483
TI  - Postpartum psychiatric disturbances as an unrecognized onset of CADASIL.

PMID- 16095486
TI  - Skin cancer as a contraindication to organ transplantation.
AB  - Skin cancer is the most common malignancy worldwide. When patients with a history
      of skin cancer present for organ transplantation, the vast majority are
      appropriate candidates. However, there is little guidance in the literature
      regarding the advisability of transplantation in patients with a history of high
      risk skin cancer. With limited allograft resources, it is important to allocate
      organs to patients who will derive the most benefit. Adverse outcomes that may be
      associated with prior skin cancer include recurrence, metastasis, or death from
      relapse or decreased quality of life from numerous new primary skin cancers. This
      review provides prognostic guidance to transplant physicians evaluating
      transplantation candidates who have a history of skin cancer.

PMID- 16095487
TI  - HLA-E expression on porcine cells: protection from human NK cytotoxicity depends
      on peptide loading.
AB  - Human NK cells lyse porcine cells and may play an important role in the cell
      mediated rejection of pig-to-human xenografts. Lysis is probably a consequence of
      the failure of human MHC-specific killer inhibitory receptors to recognize
      porcine MHC class I molecules. A majority of activated human NK cells express the
      HLA-E-specific inhibitory receptor CD94/NKG2A. The aim of this study was
      therefore to test the hypothesis that stable surface expression of HLA-E on
      porcine cells protects against xenogeneic NK-mediated cytotoxicity. Porcine
      lymphoblastoid (13 271) and endothelial (pEC) cell lines were transfected with
      constructs coding for HLA-E together with the leader sequence of HLA-B7 or -A2.
      HLA-E was correctly expressed on 13 271 cells while pEC required peptide-pulsing
      and/or IFN-gamma stimulation to express the HLA-E complex on the cell surface.
      HLA-E-expressing porcine cells were partially protected from lysis mediated by
      human polyclonal NK populations and completely protected from killing by
      NKG2Abright NK clones. In conclusion, the capability of different porcine cell
      types to express HLA-E on the cell surface can differ considerably depending
      decisively on the availability of peptides. These findings are important for the
      applicability of transgenic HLA-E expression as an approach to protect porcine
      tissues from human NK cytotoxicity.

PMID- 16095488
TI  - IFN-gamma, produced by NK cells that infiltrate liver allografts early after
      transplantation, links the innate and adaptive immune responses.
AB  - The role of NK cells following solid organ transplantation remains unclear. We
      examined NK cells in acute allograft rejection using a high responder model (DA-
      >Lewis) of rat orthotopic liver transplantation. Recipient-derived NK cells
      infiltrated liver allografts early after transplantation. Since chemokines are
      important in the trafficking of cells to areas of inflammation, we determined the
      intragraft expression of chemokines known to attract NK cells. CCL3 was
      significantly increased in allografts at 6 h post-transplant as compared to
      syngeneic grafts whereas CCL2 and CXCL10 were elevated in both syngeneic and
      allogeneic grafts. CXCL10 and CX3CL1 were significantly upregulated in allografts
      by day 3 post-transplant as compared to syngeneic grafts suggesting a role for
      these chemokines in the recruitment of effector cells to allografts. Graft
      infiltrating NK cells were shown to be a major source of IFN-gamma, and IFN-gamma
      levels in the serum were markedly increased, specifically in allograft
      recipients, by day 3 post-transplant. Accordingly, in the absence of NK cells the
      levels of IFN-gamma were significantly decreased. Furthermore, graft survival was
      significantly prolonged. These data suggest that IFN-gamma-producing NK cells are
      an important link between the innate and adaptive immune responses early after
      transplantation.

PMID- 16095489
TI  - CXCL9 antagonism further extends prolonged cardiac allograft survival in
      CCL19/CCL21-deficient mice.
AB  - CCL19/MIP-3beta and CCL21/SLC are essential for chemotactic recruitment of mature
      dendritic cells (DC) to T-cell areas of secondary lymphoid tissue. Paucity of
      lymph node T-cells (plt/plt) mice lack CCL21-serine (ser) and CCL19 expression.
      We tested plt/plt and wild type (wt) BALB/c (H2d) mice as recipients of heart or
      skin allografts from C57BL/10J (H2b) donors. Donor DC trafficking to secondary
      lymphoid tissue was markedly reduced in plt heart but not skin allograft
      recipients. Heart, but not skin grafts survived significantly longer in plt
      recipients. Accordingly, T cells from plt heart transplant recipients
      demonstrated poor anti-donor responses in ex vivo MLR, compared to wt heart or wt
      and plt skin recipients. Moreover, donor-reactive T cells from plt heart
      recipients exhibited Th2-skewing in comparison to T cells from wt heart or skin
      graft recipients. Anti-CXCL9/Mig was administered for 2 weeks post-transplant to
      determine whether impairment of activated T-cell migration could further prolong
      cardiac allograft survival in plt recipients. CXCL9-antagonism extended graft
      survival significantly only in plt mice, likely due, in part, to retention of
      alloactivated T cells in secondary lymphoid tissue/reduction of graft
      infiltrating T cells. Thus, targeting DC and activated T-cell migration
      concomitantly has additive effects in prolonging heart graft survival with
      potential for therapeutic application.

PMID- 16095490
TI  - MIP-3alpha/CCL20 in renal transplantation and its possible involvement as
      dendritic cell chemoattractant in allograft rejection.
AB  - Graft-infiltrating dendritic cells (DC) and alloreactive T lymphocytes play a
      critical role in renal allograft rejection. Renal proximal tubular epithelial
      cells (TEC) are considered as active players in the attraction of leukocytes
      during renal inflammatory responses. Macrophage inflammatory protein (MIP)
      3alpha/CCL20 is a major chemokine expressed by epithelial cells that attracts
      immature DC. In the present study, we present evidence that also the transplanted
      kidney can be a major source of MIP-3alpha/CCL20. Renal transplant recipients
      with rejection showed significantly increased excretion of urinary MIP
      3alpha/CCL20 that correlated with transplant function. The tubular staining for
      MIP-3alpha/CCL20 in renal biopsies of patients with rejection as well as in vitro
      studies with primary human TEC indicated that TEC might be responsible for the
      increased urinary MIP-3alpha/CCL20. Furthermore, MIP-3alpha/CCL20 produced by
      activated TEC was highly potent in the attraction of CD1a+CD34+-derived DC
      precursors. These data suggest a role for MIP-3alpha/CCL20 in amplification of
      the immune response during renal allograft rejection by attraction of CCR6+
      inflammatory cells, which may include DC, to the site of inflammation.

PMID- 16095491
TI  - Induction of obliterative airway disease by anti-HLA class I antibodies.
AB  - Anti-HLA class I Abs are associated with the development of bronchiolitis
      obliterans syndrome (BOS) after lung transplantation. BOS is characterized
      histologically by fibrosis and airway epithelial cell apoptosis. We have
      previously shown that anti-HLA class I Abs induce proliferation, growth factor
      production and apoptosis in airway epithelial cells in vitro. Thus, this study
      was designed to determine whether anti-HLA class I Abs alone could induce
      obliterative airway disease (OAD) in heterotopic murine tracheal allografts.
      Toward this, HLA-A*0201-transgenic tracheal allografts were transplanted into
      Rag1-deficient mice treated with the W6/32 anti-HLA class I mAb. Allografts were
      harvested at days +30, +45, +60 and +90. Allografts displayed epithelial
      metaplasia by day +45, epithelial destruction and mild cellular infiltration by
      day +60 and complete lumen obliteration and moderate cellular infiltration by day
      +90. Anti-HLA class I Abs induced the production of several growth factors and
      growth factor receptors and apoptosis of parenchymal cells in the allograft. In
      addition, anti-HLA class I Abs induced macrophages and granulocytes infiltration.
      The results from this study demonstrate that anti-HLA class I Abs play an
      important role in the pathogenesis of OAD by inducing growth factor production,
      apoptosis and chemotaxis of inflammatory cells.

PMID- 16095492
TI  - Detailed analysis of mucosal restoration of the small intestine after the
      cavitary two-layer cold storage method.
AB  - Small bowel transplantation (SBT) is associated with a high incidence of
      infectious complications because of ischemia/reperfusion (I/R) mucosal injury
      concomitant with potent immunosuppression. In this study, we evaluated whether
      the cavitary two-layer method (cTLM) could reduce I/R injury and allow early
      mucosal restoration, particularly after prolonged preservation and
      transplantation. Canine heterotopic segmental SBT was performed immediately
      without preservation (group 1), after 24-h preservation in UW solution (group 2)
      or by the cTLM (group 3). The graft samples were taken 1 h after reperfusion and
      on days 1, 4 and 7. We assessed graft mucosa with detailed microscopic and
      electromicroscopic analyses. In Group 3, histological injury and cell apoptosis
      after transplantation were significantly alleviated and rapidly recovered to a
      similar level of group 1. The mucosal restoration was morphologically completed
      within 4 days. In contrast, in group 2, more pronounced mucosal injury and
      delayed recovery were noted. Crypt cell proliferation activity was well
      maintained in groups 1 and 3 throughout the experimental period. Our
      ultrastructural analysis suggested that mitochondrial integrity achieved by the
      cTLM was a basal mechanism under the prompt mucosal restoration. The cTLM could
      reduce I/R injury, facilitate mucosal regeneration and restore the nearly normal
      structure early after SBT.

PMID- 16095493
TI  - Identification of a new member of the CD20/FcepsilonRIbeta family overexpressed
      in tolerated allografts.
AB  - We identified a novel rat gene specifically overexpressed in tolerated heart
      allografts in a model of tolerance induced by donor-specific blood transfusion
      (DST). We named this gene TORID, for tolerance-related and induced transcript. We
      show that TORID expression can be attributed to non-T cells infiltrating
      tolerated grafts. Interestingly, TORID overexpression was also observed in long
      term grafts from a different model of tolerance in which chronic rejection does
      not occur. Comparison of the predicted amino acid sequence of TORID and of its
      human counterpart LR8 showed an homology with the four-transmembrane
      CD20/FcepsilonRIbeta family proteins. We investigated TORID expression in naive
      rat immune cells and lymphoid tissues. TORID was found to be preferentially
      expressed in cells of the myeloid lineage such as macrophages and dendritic cells
      (DCs). Its expression dramatically decreased following activation/maturation.
      Similar results were obtained in human monocyte-derived DCs. Interestingly, TORID
      overexpression in bone marrow-derived DCs alters expression of MHC II and CD86
      and production of IL12p40 following activation. These results suggest that TORID
      may be involved in the control of DC maturation and may, therefore, play a role
      in the induction or maintenance of allograft tolerance.

PMID- 16095494
TI  - Circulating endothelial progenitor cells after kidney transplantation.
AB  - Circulating endothelial progenitor cells (EPCs) promote vascular repair and
      maintain integrity of the endothelial monolayer. Reduced EPCs number has been
      associated with endothelial dysfunction in various cardiovascular diseases.
      Cardiovascular disease risk is higher in renal transplant patients (RT) than the
      general population. We studied EPCs number and proliferation in RT, and examined
      the association with other cardiovascular risk factors such as reduced glomerular
      filtration rate (GFR) and LDL cholesterol. EPCs concentration was determined in
      94 RT and 39 control subjects (C) by flow cytometry. EPCs proliferation was also
      studied after 7 days in culture. EPCs concentration was significantly reduced in
      RT versus C (median 33.5 [5-177] vs. 53 [9-257] EPCs/10(5) PMN cells, p=0.006).
      EPCs proliferation was also reduced in RT versus C (mean+/-SD; 372.7+/-229.3 vs.
      539.8+/-291.3 EPCs x field, p=0.003). In multiple regression analysis, GFR, HDL,
      LDL and body weight were independent predictors of EPCs concentration in RT
      (r2=0.25, p<0.001). EPCs number is reduced in RT, particularly in patients with
      reduced GFR. Moreover, EPCs from RT studied in vitro, showed reduced
      proliferation, which is a sign of functional impairment. These alterations may be
      involved in increased cardiovascular risk of RT.

PMID- 16095495
TI  - Reperfusion-induced gene expression profiles in rat lung transplantation.
AB  - Ischemia-Reperfusion (I/R) injury after lung transplantation (LTx) can lead to
      significant morbidity and mortality in recipients. In an attempt to improve our
      understanding of molecular mechanisms of I/R injury, we examined the changes in
      gene expression levels in a rat lung transplant model using oligonucleotide
      microarrays. Lewis rat lung grafts were stored for 6 or 24 h followed by
      transplantation and reperfusion for 2 h. Lung tissues were taken before and after
      flushing the grafts, before implantation, and after 2 h of reperfusion. RNA
      samples were examined with Affymetrix rat microarray chips and RT-PCR was
      performed to validate significant changes in gene expression. Microarray analysis
      showed 404 genes that were up-regulated more than 2-fold after reperfusion
      compared to cold ischemic lungs, and 187 genes that were down-regulated. Using RT
      PCR, we confirmed the response pattern of several specific gene transcripts from
      the microarray analysis. Among these, up-regulation in transcripts of
      transcription factors, adhesion molecules, pro-coagulant factors and pro
      inflammatory cytokines were identified. The differential gene regulation during
      the I/R process can be considered as molecular signatures for the changes of
      cellular metabolism, functions and injury. Reperfusion-induced genes related to
      inflammatory response may contribute to graft dysfunction in LTx.

PMID- 16095496
TI  - Gene expression profiling in murine obliterative airway disease.
AB  - Lung and heart-lung transplantation are effective treatments for many diseases
      unresponsive to other therapy. However, long-term survival of recipients is
      limited by the development of obliterative bronchiolitis (OB). In this study,
      microarray analysis of a heterotopic mouse model of obliterative airway disease
      (OAD) was used to test the hypothesis that the expression and patterns of genes
      will correlate with specific changes in tracheal tissue developing a response to
      allotransplantation and the infiltrating cells manifesting these changes.
      Expression profiles observed were in accordance with the current paradigm of a
      predictable sequence of events, beginning with airway injury; an innate immune
      response followed by an adaptive immune response, including both cell-mediated
      and humoral components; and eventual loss of airway epithelial cells. These
      observations confirm and expand the list of genes and molecular processes that
      can be studied as potential surrogate markers or targets for intervention of OB.

PMID- 16095497
TI  - Differential role of TGF-beta1/bFGF and ET-1 in graft fibrosis in heart failure
      patients.
AB  - Collagen overproduction characteristic for dilated cardiomyopathy (DCM) is
      coregulated by endothelin (ET)-1, transforming growth factor (TGF)-beta1, basic
      fibroblast growth factor (bFGF) and matrix metalloproteases (MMPs). Whether these
      molecules affect grafts transplanted to heart failure patients is unknown. In 67
      idiopathic DCM patients, 31 patients with ischemic cardiomyopathy (ICM) and 16
      controls, the myocardial bFGF, TGF-beta1, pro-collagen (PrCol) type 1 (PrCol1
      alpha1, -alpha2) and MMP expressions were examined using real-time RT-PCR or
      Western blotting. mRNA expression was measured in grafts for 1 year. TGF
      beta1/bFGF stimulation or gene silencing was used to examine their effect on
      collagen synthesis in cardiac tissue cultures. TGF-beta1 and PrCol1 were
      upregulated in DCM only, while bFGF was upregulated in both groups versus
      controls. TGF-beta1 downregulated MMP-1 and upregulated collagen 1, whereas bFGF
      upregulated MMP-13 in DCM tissue. Post-transplant PrCol1-alpha1, -alpha2 and ET-1
      mRNA increased over time in grafts of DCM patients only, while other factors
      returned to control baseline levels in DCM and ICM. These data indicate that
      cardiac transplantation corrects the dysregulated TGF/bFGF/MMP-1/MMP-13, but not
      the excess collagen and ET-1 synthesis in cardiac grafts transplanted to DCM
      patients. ET-1 might be a major pathologic trigger for graft fibrosis in DCM.

PMID- 16095498
TI  - Predictive performance of renal function equations in renal transplant
      recipients: an analysis of patient factors in bias.
AB  - Creatinine-based equations are available to estimate GFR. After renal
      transplantation body composition usually changes, thus specific validation is
      required for transplant recipients. Nine equations were compared with iothalamate
      glomerular filtration rate (GFR) at 1 year after transplantation in 798
      recipients. Equations were analyzed for precision, bias and accuracy. Sources of
      bias were analyzed by univariate and multivariate analysis, with body mass index
      (BMI), age and sex as independent variables and bias as dependent variable. Four
      hundred and seventy-eight patients were studied to assess whether the equations
      can be used to monitor renal function over time. Predictive performance was
      modest for all equations. MDRD and Jelliffe 2 were the best predictors of GFR.
      Bias was significantly related to BMI, age and gender in most equations.
      Multivariate analysis confirmed their independent contribution to the bias of
      MDRD, Jelliffe 2 and most other equations. Over time, bias was relatively stable
      at group level, but predictive performance in individuals was modest. The
      predictive performance of renal function equations is modest in renal
      transplants, which hampers their use for accurate assessment of renal function in
      the individual. The role of patient factors in the systematic error suggests that
      development of better equations should be feasible by better incorporation of
      these factors.

PMID- 16095499
TI  - Activated protein C reduces graft neutrophil activation in clinical renal
      transplantation.
AB  - We studied the role of endogenous activated protein C (APC), the major
      physiological anti-coagulant with concomitant anti-inflammatory properties, on
      ischemia/reperfusion (I/R) in 45 patients participating in a larger trial
      comparing three immunosuppressive protocols in cadaveric renal transplantation:
      perioperative anti-thymocyte globulin (ATG, Fresenius AG, Bad Homburg, Germany),
      perioperative basiliximab and conventional triple therapy. Blood samples for
      assessing plasma APC, protein C, and lactoferrin concentrations, neutrophil CD11b
      and L-selectin expressions and blood leukocyte differential counts were obtained
      preoperatively and before reperfusion from central venous cannula, complemented
      with simultaneous samples from iliac artery and graft vein for calculation of
      transrenal differences (Delta) of study parameters at 1 and 5 min after
      reperfusion. Unlike basiliximab or conventional therapy groups, ATG infusion
      induced a substantial increase in plasma APC concentration (119 [88-144]% before
      infusion vs. 232 [85-1246]% after infusion, p<0.001), resulting in renal graft
      sequestration of APC at 1 min after reperfusion (Delta=-72 [-567 to 12]%,
      p<0.001). Graft APC consumption was associated with transrenal reduction of
      neutrophil activation markers (L-selectin r=0.7, p=0.01; lactoferrin r=-0.6,
      p=0.02; CD11b r=-0.8, p=0.001), and with both warm (r=0.6, p=0.01) and cold
      ischemia time (r=0.6, p=0.02) and donor age (r=0.6, p=0.01). These findings
      suggest that APC has an anti-inflammatory role in I/R injury in clinical renal
      transplantation.

PMID- 16095500
TI  - Donor origin of BK virus in renal transplantation and role of HLA C7 in
      susceptibility to sustained BK viremia.
AB  - In a previous study, we performed serial BK virus (BKV), polymerase chain
      reaction (PCR) and detected active BKV infection in 70 (35.4%) of 198 renal
      transplant recipients. In the current study, pre-transplant donor and recipient
      samples were analyzed for BKV antibody titer and HLA alleles. Donor antibody
      titer was inversely proportional to onset of viruria, p<0.001, directly
      proportional to duration of viruria, p=0.014 and directly proportional to peak
      urine viral titer p=0.005. Recipient pairs receiving kidneys from the same donor
      were concordant for BKV infection, p=0.017, and had matched sequences of segments
      of the NCCR and VP1 genes that tended to vary among recipients of kidneys from
      different donors. We did not see an association of HLA A, B, or DR, HLA allele
      mismatches or total HLA mismatches and BK infection. However, all 11 recipients
      with sustained BK viremia received kidneys from donors lacking HLA C7, and 10
      recipients also lacked C7. These findings derive from the largest and most
      comprehensive prospective study of BKV infection in renal transplant recipients
      performed to date. Our data support donor origin for early BKV infection in
      kidney transplant recipients, and suggest that a specific HLA C locus may be
      associated with failure to control BKV infection.

PMID- 16095501
TI  - Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD
      incidence in pediatric liver transplant recipients.
AB  - Epstein-Barr virus (EBV) is a common viral infection in pediatric liver
      transplant patients and can lead to development of post-transplant
      lymphoproliferative disorder (PTLD). Differing studies have used
      immunosuppression reduction, antiviral medications or i.v. CMV-immunogloublin for
      EBV prevention and treatment. The purpose of this study was to determine whether
      implementation of a protocol for frequent EBV monitoring and EBV viral load
      driven immunosuppression reduction could decrease the incidence of PTLD in our
      patient population. All data were prospectively collected between 2001 and 2004
      at a single institution. Seventy-three patients were entered into the study.
      Patients were divided into a historical control group (pre-2001, 30 patients) and
      a treatment group (post-2001, 43 patients). Approximately 1271 blood samples of
      73 patients were collected between 2001 and 2004. Eleven out of 43 patients
      received immunosuppression tapering due to high EBV viral loads (>4000
      copies/microg DNA). One patient developed allograft rejection after
      immunosuppression modulation. Prior to 2001, the incidence of PTLD at our
      institution was 16%. After instituting a protocol for EBV monitoring, the
      incidence of PTLD decreased to 2% (p-value<0.05). These findings illustrate that
      frequent EBV viral load monitoring and preemptive immunosuppression modulation
      have an integral role in preventing PTLD in the pediatric liver transplant
      population.

PMID- 16095502
TI  - Living-donor liver transplantation for hepatoblastoma.
AB  - Hepatoblastoma is the most common malignant liver tumor in children. Recently,
      liver transplantation has been indicated for unresectable hepatoblastoma. We
      retrospectively reviewed 14 children with a diagnosis of hepatoblastoma who had
      undergone living-donor liver transplantation (LDLT) at Kyoto University Hospital.
      During the period from June 1990 to December 2004, 607 children underwent LDLT.
      Of these interventions, 2.3% were performed for hepatoblastoma. Based on
      radiological findings, the pre-treatment extent of disease (PRETEXT) grouping was
      used for pre-treatment staging of the tumor. There were grade III in seven
      patients and grade IV in seven patients. Thirteen patients received chemotherapy,
      and seven underwent hepatectomy 11 times. Immunosuppressive treatment consisted
      of tacrolimus monotherapy in 11 patients. Actuarial 1- and 5-year graft and
      patient survival rates were 78.6% and 65.5%. The poor prognostic factors were
      macroscopic venous invasion and extrahepatic involvement with 1-year and 5-year
      survival rates of 33.0% and 0%. Pediatric patients without these factors showed
      an acceptable 5-year survival rate of 90.9%. LDLT provides a valuable alternative
      with excellent results in children with hepatoblastoma because it allows optimal
      timing of the liver transplantation, given the absence of delay between the
      completion of chemotherapy and planned liver transplantation.

PMID- 16095503
TI  - Combined therapy with atorvastatin and calcineurin inhibitors: no interactions
      with tacrolimus.
AB  - Increased systemic exposure to statins and consequent risk for complications has
      been reported in patients concomitantly treated with cyclosporin A (CsA). This
      has been ascribed to inhibition of drug catabolism by cytochrome P450 3A4
      (CYP3A4) or drug transport by P-glycoprotein (PGP) and organic anion transporting
      polypeptide (OATP1B1). It is not known whether the combination of statins and
      tacrolimus (Tac) also suffers from this drawback. Therefore, a pharmacokinetic
      study of atorvastatin and its metabolites was performed in 13 healthy volunteers
      after 4 days' treatment, and after short (12 h) concomitant exposure to CsA and
      Tac. A complementary assessment of overall CYP, and hepatic and intestinal
      CYP3A4+PGP activity was performed after each treatment episode and compared to
      baseline (no drugs). Systemic exposure to atorvastatin acid and its metabolites
      was significantly increased when administered with CsA. In contrast, intake of
      Tac did not have any impact on atorvastatin pharmacokinetics. Concomitantly, a
      profound decrease of hepatic and intestinal PGP and an increase of intestinal
      CYP3A4 were noted with CsA, whereas no effect was seen after atorvastatin therapy
      with or without Tac. Based on these findings treatment with Tac appears a safer
      option for patients needing a combination of statins and calcineurin inhibitors.

PMID- 16095504
TI  - Regional variations in peer reviewed liver allocation under the MELD system.
AB  - The Model for End-Stage Liver Disease (MELD) is used to assign priority for liver
      transplantation candidates. The Organ Procurement and Transplantation Network
      (OPTN) approved recognized exceptional diagnoses (RED's) for which MELD fails to
      accurately measure priority. Centers can request increased MELD points in cases
      not recognized by this policy (non-RED's). Our aim was to compare regional
      practices to justify non-RED requests for MELD adjustments. The UNOS/OPTN
      database was queried to extract all adult cases for which a non-RED MELD
      adjustment was requested from 2/27/02 until 8/27/03. The data were stratified by
      region and justification. Data for 29,510 listings were available. 26,947 had
      complete diagnosis information. There were 827 non-RED requests of which 477
      (57.7%) petitions were approved by the regional review boards (RRBs). The
      approval rate varied significantly among regions (range: 28-75%, p<0.0001). The
      most common non-RED's were complications of portal hypertension (48%). The
      percentage of patients listed with non-RED's varied significantly among regions
      (0.7-8.3 %, p<0.0001), as did the proportion of patients transplanted with non
      RED's (2.1-31.9%, p<0.0001). Demographics did not differ among regions requesting
      non-REDs.Widespread regional variations exist in the handling of requests for non
      REDs. These variations point to the need for reform to standard exception
      criteria.

PMID- 16095505
TI  - Association of CD20+ infiltrates with poorer clinical outcomes in acute cellular
      rejection of renal allografts.
AB  - We undertook a study to ascertain the relationship between the presence of CD20
      positive B-lymphocytes in renal allografts undergoing acute cellular rejection
      and graft survival. We identified 27 patients transplanted between January 1,
      1998 and December 31, 2001, with biopsy-proven Banff 1-A or Banff 1-B rejection
      in the first year after transplantation, and stained the specimens for CD20 and
      C4d. At least 4 years of follow-up data were available for each patient studied.
      Six patients had CD20-positive B-cell clusters in the interstitium, and 21
      patients were negative for CD20 infiltrates. The CD20-positive group was
      significantly more likely to have steroid-resistant rejection and reduced graft
      survival compared to CD20-negative controls. This study supports prospective
      identification of CD20-positive B-cell clusters in biopsy-proven rejection and
      offers a therapeutic rationale for a trial of monoclonal anti-CD20 antibody in
      such patients.

PMID- 16095506
TI  - Long-term outcome of deceased donor renal transplants correlates with the 30-day
      creatinine reduction ratio.
AB  - A simplified model to correlate early allograft function with long-term allograft
      survival in recipients of deceased donor renal transplants (DDRT) remains
      challenging. We propose here a novel approach, using the change from the
      pretransplant creatinine to the 30-day posttransplant creatinine. The outcomes of
      153 consecutive DDRT performed at our center between January 1998 and March 2001
      were reviewed. The percentage change in creatinine from the pretransplant to 1
      month posttransplant, termed here, the creatinine reduction ratio (CRR), was
      calculated as follows: (pretransplant creatinine-creatinine at 1
      month)/pretransplant creatinine *100%. Patients were divided as follows: group 1
      CRR>or=67% and group 2<67%. Group 1 had a graft survival at 1 and 5 years of 100%
      and 89.1% versus 88% and 69.1% for group 2 (log-rank p=0.0008). The risk ratio
      for graft loss during the follow-up period was four times lower for the patients
      on group 1. Using the Cox hazards model to compare CRR>or=67% with determinants
      of long-term outcome, the risk ratio of graft loss during the observational
      period was 0.26 (p=0.001). The creatinine reduction ratio, when stratified by a
      level of >or=67% has a strong correlation with superior long-term allograft
      survival in recipients of DDRT.

PMID- 16095507
TI  - Homocysteine-lowering therapy and early progression of transplant vasculopathy: a
      prospective, randomized, IVUS-based study.
AB  - Although observational studies suggest that hyperhomocysteinemia may be a risk
      factor for coronary allograft vasculopathy (CAV), prospective data on
      homocysteine-lowering interventions and CAV development are lacking. We,
      therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of
      5-methyl-tetrahydrofolate (n=22), or standard therapy (control group, n=22) to
      investigate the effect of homocysteine lowering on the change in coronary intimal
      hyperplasia during the first 12 months after transplant, as detected by intra
      vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was
      lower in folate-treated patients (p<0.001), coronary intimal area increased
      similarly in the two groups (p>0.4). Conversely, hypercholesterolemia and
      cytomegalovirus infection were both associated with increased intimal hyperplasia
      (p<0.04), independently from folate intake. Sub-group analysis revealed that
      folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia
      before randomization (n=19; p=0.02), but increased intimal hyperplasia in
      patients with normal homocysteine plasma concentrations (p=0.02). This bimodal
      effect of folate therapy persisted significantly after adjusting for
      cytomegalovirus infection and hypercholesterolemia. Despite effective in prevent
      hyperhomocysteinemia after heart transplantation, folate therapy does not seem to
      affect early CAV onset. However, sub-group analysis suggests that folate therapy
      may delay CAV development only in patients with baseline hyperhomocysteinemia,
      while may favor CAV progression in recipients with normal baseline
      homocysteinemia.

PMID- 16095508
TI  - Serial ten-year follow-up of HLA and MICA antibody production prior to kidney
      graft failure.
AB  - The role of HLA antibodies in chronic allograft rejection was examined utilizing
      a unique resource of sera collected annually and stored over a 12-year period
      from patients with rejected or retained grafts. In patients selected for not
      having preformed HLA antibodies, 679 postoperative serial serum samples from 39
      patients who rejected their grafts and 26 with functioning grafts were tested for
      HLA Class I and Class II antibodies by flow cytometry and for MICA antibodies by
      cytotoxicity on recombinant cell lines. HLA antibodies were found in 72% of
      patients who rejected grafts, compared to 46% with functioning transplants
      (p<0.05). In addition, the incidence of IgG HLA plus MICA antibodies was higher
      (77%) among those with failed transplants than those with functioning transplants
      (42%) (p<0.01). Finally, if patients with IgM anti-HLA antibodies were included,
      95% of the 39 patients who rejected their grafts had HLA or MICA antibodies,
      compared to 58% with functioning grafts (p<0.01). Patients who rejected
      transplants had HLA and MICA antibodies more frequently than those with
      functioning grafts. These antibodies found in the peripheral circulation, were
      not necessarily donor-specific, but their association with failure is consistent
      with a causality hypothesis.

PMID- 16095509
TI  - Sirolimus in combination with tacrolimus is associated with worse renal allograft
      survival compared to mycophenolate mofetil combined with tacrolimus.
AB  - Cyclosporine (CsA) nephrotoxicity is enhanced by sirolimus (SRL). Tacrolimus is
      perceived to be less nephrotoxic than CsA, and therefore, CsA has been largely
      replaced by tacrolimus (TAC) when calcineurin inhibitors are used with SRL. We
      analyzed 44 915 adult renal transplants in the Scientific Renal Transplant
      Registry (SRTR) from 2000 to 2004. Three thousand five hundred twenty-four (7.8%)
      patients received a baseline immunosuppressive regimen of TAC/SRL, with an
      inferior overall (log-rank p<0.001) and death-censored graft survival (p<0.001)
      as compared to TAC/MMF (N=27 007). This effect was confirmed in multivariate Cox
      models; the adjusted hazard ratio (AHR) for overall graft loss with TAC/SRL was
      1.47 (95% CI=1.32, 1.63) and for CsA/SRL 1.38 (95% CI=1.20, 1.59) relative to
      TAC/MMF. These effects were most apparent in high-risk transplants. Six-month
      acute rejection rates were low (11.5-12.6%) and not different between groups. In
      summary, national data indicate that TAC/SRL as compared to TAC/MMF is associated
      with significantly worse renal allograft survival in all subgroups of patients
      and, in particular, higher-risk transplants. These results have to be interpreted
      in the context of the inherent limitations of any retrospective database analysis
      and evaluated in context with data from prospective clinical trials.

PMID- 16095510
TI  - Early low-grade proteinuria: causes, short-term evolution and long-term
      consequences in renal transplantation.
AB  - Proteinuria 1 year after transplantation is associated with poor renal outcome.
      It is unclear whether low-grade (<1 g/24 h) proteinuria earlier after
      transplantation and its short-term change affect long-term graft survival. The
      effects of proteinuria and its change on long-term graft survival were
      retrospectively assessed in 484 renal transplant recipients. One- and 3-month
      proteinuria correlated with donor age, donor cardiovascular death, prolonged cold
      and warm ischemia times and acute rejection. One- and 3-month proteinuria (per
      0.1 g/24 h, hazard ratio (HR): 1.07 and 1.15, p<0.0001)-especially low-grade
      proteinuria (HR: 1.20 and 1.26, p<0.0001)-were powerful, independent predictors
      of graft loss. Its short-term reduction correlated with arterial pressure (AP)
      (the lower the 3-month diastolic and 12-month systolic AP, the lower the risk of
      increasing proteinuria during 1-3 months and 3-12 months periods, respectively:
      Odds ratio (OR) per 10 MmHg: 0.78, p=0.01 and 0.85, respectively, p=0.02), and
      was associated with decreased long-term graft loss (per 0.1 g/24 h: HR: 0.88 and
      0.98, respectively, p<0.0001), independently of initial proteinuria. Early low
      grade proteinuria due to pre-transplant renal lesions, ischemia-reperfusion and
      immunologic injuries is a potent predictor of graft loss. Short-term reduction in
      proteinuria is associated with improved long-term graft survival.

PMID- 16095511
TI  - The life-years saved by a deceased organ donor.
AB  - Understanding the additional life-years given to patients by deceased organ
      donors is necessary as substantial investments are being proposed to increase
      organ donation. Data were drawn from the Scientific Registry of Transplant
      Recipients. All patients placed on the wait-list as eligible to receive or
      receiving a deceased donor solid organ transplant between 1995 and 2002 were
      studied. The benefit of transplant was determined by the difference in the
      expected survival experiences of transplant recipients and candidates expecting
      transplant soon. An average organ donor provides 30.8 additional life-years
      distributed over an average 2.9 different solid organ transplant recipients,
      whereas utilization of all solid organs from a single donor provides 55.8
      additional life-years spread over six organ transplant recipients. The relative
      contribution of the different organs to the overall life-year benefit is higher
      for liver, heart and kidney, and lowest for lung and pancreas. The life-year
      losses from unprocured and unused organs are comparable to suicide, congenital
      anomalies, homicide or perinatal conditions and half that of HIV. Approximately
      250,000 additional life-years could be saved annually if consent for potential
      deceased donors could be increased to 100%. Therefore, increasing organ donation
      should be considered among our most important public health concerns.

PMID- 16095512
TI  - The economic impact of MELD on liver transplant centers.
AB  - Adoption of the model for end stage liver disease (MELD) system prioritized
      patients awaiting liver transplant (LT) by severity of illness including
      progressive renal dysfunction. Unfortunately, current reimbursement for LT is not
      adjusted by severity of illness or need for simultaneous liver-kidney
      transplantation (LKT). This study examines hospital cost and reimbursement for LT
      and LKT to determine the effect of MELD on transplant center (TC) financial
      outcomes given current reimbursement practices as well as DRG outlier threshold
      limits. LT was performed for 86 adults prior to and 127 following the
      implementation of MELD. Between the eras, there was a substantial increase in the
      average laboratory MELD score (17.1 to 20.7 p=0.004) and percentage of LKTs
      performed (5.8% to 17.3% p=0.01). Increasing MELD score was associated with
      higher costs ($4309 per MELD point p<0.001) and decreasing TC net income ($1512
      per MELD point p<0.001). In patients not achieving the Medicare outlier status,
      predicted net loss was $17,700 for high-MELD patients and $19,133 for those
      needing LKT. In conclusion, contractual reimbursement agreements that are not
      indexed by severity of disease may not reflect the increased costs resulting from
      the MELD system. Even with outlier thresholds, Medicare reimbursement is
      inadequate resulting in a net loss for the TC.

PMID- 16095513
TI  - The Dutch national living donor kidney exchange program.
AB  - The wait time for deceased-donor kidney transplantation has increased to 4-5
      years in the Netherlands. Strategies to expand the donor pool include a living
      donor kidney exchange program. This makes it possible that patients who cannot
      directly receive a kidney from their intended living donor, due to ABO blood type
      incompatibility or a positive cross match, exchange donors in order to receive a
      compatible kidney. All Dutch kidney transplantation centers agreed on a common
      protocol. An independent organization is responsible for the allocation, cross
      matches are centrally performed and exchange takes place on an anonymous basis.
      Donors travel to the recipient centers. Surgical procedures are scheduled
      simultaneously. Sixty pairs participated within 1 year. For 9 of 29 ABO blood
      type incompatible and 17 of 31 cross match positive combinations, a compatible
      pair was found. Five times a cross match positive couple was matched to a blood
      type incompatible one, where the recipients were of blood type O. The living
      donor kidney exchange program is a successful approach that does not harm any of
      the candidates on the deceased donor kidney waitlist. For optimal results, both
      ABO blood type incompatible and cross match positive pairs should participate.

PMID- 16095514
TI  - A computer match program for paired and unconventional kidney exchanges.
AB  - The number of renal transplants can be increased by implementing an exchange
      program involving donor-recipient pairs for whom the donors are each incompatible
      with their original patient but compatible with each other's patient. The number
      can be further increased if the exchanges are not limited to ABO incompatible
      pairs or combinations of two donor-recipient pairs. However, as the number of
      donor-recipient pairs willing to participate in such a program increases, there
      is a substantial increase in both the time taken to identify such matches and the
      potential for error. We have developed a computer program that accounts for ABO
      and HLA compatibility and is not limited to two-way exchanges. With our database
      of 60 patients and 83 donors, we have been able to identify 122 two-way and 1230
      three-way exchanges with an average run time of 30 s.

PMID- 16095515
TI  - Syngeneic living-donor liver transplantation for hemangioendothelioma: a clinical
      model for studying liver regeneration.
AB  - A 22-year-old Caucasian patient underwent living-donor liver transplantation
      (LDLT) for hepatic hemangioendothelioma in a healthy liver. The organ donor was
      his monozygotic twin brother. Surgery was uneventful in both donor and recipient,
      who received the same postoperative treatment (i.e. no immunosuppression for the
      recipient). Although both donor and recipient achieved a full liver function
      recovery, the volume of the recipient's graft increased much more than the
      donor's residual liver in the first postoperative month (1.6-fold vs. 1.2-fold).
      This different growth rate correlated with growth hormone (GH)/insulin growth
      factor (IGF) axis dynamics: the donor had significantly lower insulin-like growth
      factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth
      factor binding protein 3 (IGFBP-3) values than the recipient on postoperative
      days (POD) 3-30, although they had similar GH values. Other potential
      regenerative factors, e.g. tumor necrosis alpha, interleukin 6 (IL-6), insulin
      and C peptide did not correlate with liver regeneration rate. The particular
      endocrine picture of the graft may be explained by a modified GH-hepatocyte
      interaction due to cold ischemia during preservation resulting in a higher IGF
      production. Whether this is a potential molecular tool by means of which
      transplanted partial livers promote their regeneration remains to be seen in a
      larger number of patients.

PMID- 16095516
TI  - Successful renal transplantation during pregnancy.
AB  - Little is known about the implications of performing a renal transplant on a
      patient who is already pregnant. This case study reports a successful outcome of
      pregnancy, diagnosed coincidentally following renal transplantation at 13 weeks
      gestation. The recipient was a 23-year-old woman with chronic kidney disease who
      received a live-related renal transplant from her father. Pregnancy was
      discovered at routine ultrasound scanning of the renal allograft at 5 days
      posttransplant and estimated at 13 weeks gestation. She received ciclosporin
      monotherapy as immunosuppression throughout the pregnancy, and was given
      valacyclovir as prophylaxis against cytomegalovirus (CMV) infection. Renal
      function remained stable throughout the pregnancy, which progressed normally,
      resulting in the vaginal delivery of a healthy, liveborn male infant at 37 weeks
      gestation. This case study demonstrates that transplantation during pregnancy can
      have a successful outcome.

PMID- 16095517
TI  - Proteinuria developing after clinical islet transplantation resolves with
      sirolimus withdrawal and increased tacrolimus dosing.
AB  - Sirolimus is a potent immunosuppressant, which may permit the avoidance of
      nephrotoxic calcineurin inhibitors (CNI). However, cases of proteinuria
      associated with sirolimus have been reported following renal transplantation.
      Here, we report three cases of proteinuria (1, 2 and 7 g/day) developing during
      therapy with sirolimus plus low-dose tacrolimus following clinical islet
      transplantation (CIT) in type I diabetic subjects. The proteinuria resolved after
      discontinuation of sirolimus, substituted by mycophenolate mofetil (MMF) combined
      with an increased dose of tacrolimus. A renal biopsy in one case indicated only
      the presence of diabetic glomerulopathy. Five other CIT recipients developed
      microalbuminuria while on sirolimus which all resolved after switching to
      tacrolimus and MMF. The resolution of proteinuria from the native kidneys of CIT
      recipients after the discontinuation sirolimus suggests that, at least in some
      individuals, sirolimus itself may have adverse renal effects. Sirolimus should be
      used cautiously with close monitoring for proteinuria or renal dysfunction.

PMID- 16095518
TI  - Severe course of primary hyperoxaluria and renal failure after domino hepatic
      transplantation.
AB  - We report herein a domino orthotopic liver transplantation (LT), from a 38-year
      old woman undergoing liver-kidney transplantation (LKT) for primary hyperoxaluria
      type I (PH1) to a recipient with cirrhosis and hepatocellular carcinoma. Delayed
      onset of PH1 and renal failure and 10% residual alanine-glyoxylate
      aminotransferase (AGT) activity in domino liver justified its use for domino
      procedure. The clinical course after LKT was similar to that described in other
      series, including ours. Renal function started promptly and maintained despite
      sustained hyperoxaluria from dissolution of oxalotic deposits. Conversely, the
      domino recipient manifested severe hyperoxaluria and developed nephrolithiasis
      and renal insufficiency with rapid progression over 2 months. A new LT resulted
      in slow decrease of oxaluria and improvement of renal function. Therefore, PH1
      behaved quite differently in these two patients, leading us to conclude that
      domino LT using livers from PH1 patients should be considered very carefully,
      only as a bridge to definitive LT in recipients with critical clinical
      conditions.

PMID- 16095519
TI  - Analysis of exposure-response relationship in everolimus-cyclosporine combination
      regimen.

PMID- 16095520
TI  - Therapeutic drug monitoring for everolimus in heart transplant recipients: flawed
      model or a model for future use?

PMID- 16095521
TI  - Transplantation of a liver graft from a living donor with early gastric cancer.

PMID- 16095523
TI  - In defense of steroids.

PMID- 16095524
TI  - Use of the splenic vessels for an ABO incompatible renal transplant in a patient
      with thrombosis of the vena cava.

PMID- 16095525
TI  - Improving survival rates of newborn infants in South Africa.
AB  - BACKGROUND: The number, rates and causes of early neonatal deaths in South Africa
      were not known. Neither had modifiable factors associated with these deaths been
      previously documented. An audit of live born infants who died in the first week
      of life in the public service could help in planning strategies to reduce the
      early neonatal mortality rate. METHODS: The number of live born infants weighing
      1000 g or more, the number of these infants who die in the first week of life,
      the primary and final causes of these deaths, and the modifiable factors
      associated with them were collected over four years from 102 sites in South
      Africa as part of the Perinatal Problem Identification Programme. RESULTS: The
      rate of death in the first week of life for infants weighing 1000 g or more was
      unacceptably high (8.7/1000), especially in rural areas (10.42/1000). Intrapartum
      hypoxia and preterm delivery are the main causes of death. Common modifiable
      factors included inadequate staffing and facilities, poor care in labour, poor
      neonatal resuscitation and basic care, and difficulties for patients in accessing
      health care. CONCLUSION: Practical, affordable and effective steps can be taken
      to reduce the number of infants who die in the first week of life in South
      Africa. These could also be implemented in other under resourced countries.

PMID- 16095526
TI  - Illegal births and legal abortions--the case of China.
AB  - BACKGROUND: China has a national policy regulating the number of children that a
      woman is allowed to have. The central concept at the individual level application
      is "illegal pregnancy". The purpose of this article is to describe and
      problematicize the concept of illegal pregnancy and its use in practice. METHODS:
      Original texts and previous published and unpublished reports and statistics were
      used. RESULTS: By 1979 the Chinese population policy was clearly a policy of
      controlling population growth. For a pregnancy to be legal, it has to be defined
      as such according to the family-level eligibility rules, and in some places it
      has to be within the local quota. Enforcement of the policy has been pursued via
      the State Family Planning (FP) Commission and the Communist Party (CP), both of
      which have a functioning vertical structure down to the lowest administrative
      units. There are various incentives and disincentives for families to follow the
      policy. An extensive system has been created to keep the contraceptive use and
      pregnancy status of all married women at reproductive age under constant
      surveillance. In the early 1990s FP and CP officials were made personally
      responsible for meeting population targets. Since 1979, abortion has been
      available on request, and the ratio of legal abortions to birth increased in the
      1980s and declined in the 1990s. Similar to what happens in other Asian countries
      with low fertility rates and higher esteem for boys, both national- and local
      level data show that an unnaturally greater number of boys than girls are
      registered as having been born. CONCLUSION: Defining a pregnancy as "illegal" and
      carrying out the surveillance of individual women are phenomena unique in China,
      but this does not apply to other features of the policy. The moral judgment
      concerning the policy depends on the basic question of whether reproduction
      should be considered as an individual or social decision.

PMID- 16095527
TI  - Three subsets of sequence complexity and their relevance to biopolymeric
      information.
AB  - Genetic algorithms instruct sophisticated biological organization. Three
      qualitative kinds of sequence complexity exist: random (RSC), ordered (OSC), and
      functional (FSC). FSC alone provides algorithmic instruction. Random and Ordered
      Sequence Complexities lie at opposite ends of the same bi-directional sequence
      complexity vector. Randomness in sequence space is defined by a lack of
      Kolmogorov algorithmic compressibility. A sequence is compressible because it
      contains redundant order and patterns. Law-like cause-and-effect determinism
      produces highly compressible order. Such forced ordering precludes both
      information retention and freedom of selection so critical to algorithmic
      programming and control. Functional Sequence Complexity requires this added
      programming dimension of uncoerced selection at successive decision nodes in the
      string. Shannon information theory measures the relative degrees of RSC and OSC.
      Shannon information theory cannot measure FSC. FSC is invariably associated with
      all forms of complex biofunction, including biochemical pathways, cycles,
      positive and negative feedback regulation, and homeostatic metabolism. The
      algorithmic programming of FSC, not merely its aperiodicity, accounts for
      biological organization. No empirical evidence exists of either RSC of OSC ever
      having produced a single instance of sophisticated biological organization.
      Organization invariably manifests FSC rather than successive random events (RSC)
      or low-informational self-ordering phenomena (OSC).

PMID- 16095528
TI  - Development of novel heminested PCR assays based on mitochondrial 16s rRNA gene
      for identification of seven pecora species.
AB  - BACKGROUND: Characterization of molecular markers and the development of better
      assays for precise and rapid detection of wildlife species are always in demand.
      This study describes a set of seven novel heminested PCR assays using specific
      primers designed based on species-specific polymorphism at the mitochondrial 16S
      rRNA gene for identification of Blackbuck, Goral, Nilgai, Hog deer, Chital,
      Sambar and Thamin deer. RESULTS: The designed heminested PCR assays are two
      consecutive amplifications of the mitochondrial 16S rRNA gene. In the first
      stage, approximately 550 bp region of the 16S rRNA gene was amplified by PCR
      using template DNA and universal primers. In the second stage, a species-specific
      internal region of the 16S rRNA gene was amplified by PCR using the amplicon of
      the first PCR along with one universal primer and another species-specific primer
      as the reverse or forward primer. The amplicon generated after two consecutive
      amplifications was highly unique to target species. These assays were
      successfully validated for sensitivity, specificity, and ruggedness under a wide
      range of conditions. CONCLUSION: The validation experiments confirm that the
      designed heminested PCR assays for identification of the seven species are highly
      specific, sensitive, reliable and provide a reproducible method allowing analysis
      of low copy number DNA recovered from decomposed or highly processed tissues. The
      assays for identification of other species could be devised by extrapolating the
      principle of designed heminested PCR.

PMID- 16095529
TI  - A role for MCP-1/CCR2 in interstitial lung disease in children.
AB  - BACKGROUND: Interstitial lung diseases (ILD) are chronic inflammatory disorders
      leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1) promotes
      collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from
      pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and
      CCR2+ T cells accumulate in pediatric ILD and are related to disease severity.
      METHODS: Bronchoalveolar lavage fluid was obtained from 25 children with ILD and
      10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines
      were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+,
      CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry. RESULTS: CCR2+
      T cells and MCP-1 levels were significantly elevated in children with ILD and
      correlated with forced vital capacity, total lung capacity and ILD disease
      severity scores. Children with lung fibrosis had significantly higher MCP-1
      levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic
      children. CONCLUSION: The results indicate that pulmonary CCR2+ T cells and MCP-1
      contribute to the pathogenesis of pediatric ILD and might provide a novel target
      for therapeutic strategies.

PMID- 16095530
TI  - Clarifying the role of three-dimensional transvaginal sonography in reproductive
      medicine: an evidenced-based appraisal.
AB  - This overview describes and illustrates the clinical applications of three
      dimensional transvaginal sonography in reproductive medicine. Its main
      applications include assessment of uterine anomalies, intrauterine pathology,
      tubal patency, polycystic ovaries, ovarian follicular monitoring and endometrial
      receptivity. It is also useful for detailed evaluation of failed and/or ectopic
      pregnancy. Three-dimensional color Doppler sonography provides enhanced depiction
      of uterine, endometrial, and ovarian vascularity.

PMID- 16095531
TI  - No significant role for beta tubulin mutations and mismatch repair defects in
      ovarian cancer resistance to paclitaxel/cisplatin.
AB  - BACKGROUND: The mechanisms of chemoresistance in ovarian cancer patients remain
      largely to be elucidated. Paclitaxel/cisplatin combination is the standard
      chemotherapeutic treatment for this disease, although some patients do not
      respond to therapy. Our goals were to investigate whether TUBB mutations and
      mismatch repair defects underlie paclitaxel and cisplatin resistance. METHODS:
      Thirty-four patients with primary ovarian carcinomas (26 serous and eight clear
      cell carcinomas) treated with paclitaxel/cisplatin were analysed. TUBB exon 4 was
      analysed by nested PCR after a first round PCR using intronic primers.
      Microsatellite analysis was performed with the quasimonomorphic markers BAT 26
      and BAT 34. RESULTS: Twenty-two of the 34 ovarian cancers (64.7%) presented
      residual tumour after surgery, seven of which (7/22; 31.8%) were shown to be
      chemoresistant (five serous and two clear cell tumours). Sequence analysis did
      not find any mutation in TUBB exon 4. Microsatellite instability was not detected
      in any of the ovarian carcinomas. CONCLUSION: We conclude that TUBB exon 4
      mutations and mismatch repair defects do not play a significant role in
      paclitaxel/cisplatin resistance.

PMID- 16095532
TI  - Algorithm for identifying and separating beats from arterial pulse records.
AB  - BACKGROUND: This project was designed as an epidemiological aid-selecting tool
      for a small country health center with the general objective of screening out
      possible coronary patients. Peripheral artery function can be non-invasively
      evaluated by impedance plethysmography. Changes in these vessels appear as good
      predictors of future coronary behavior. Impedance plethysmography detects volume
      variations after simple occlusive maneuvers that may show indicative
      modifications in arterial/venous responses. Averaging of a series of pulses is
      needed and this, in turn, requires proper determination of the beginning and end
      of each beat. Thus, the objective here is to describe an algorithm to identify
      and separate out beats from a plethysmographic record. A secondary objective was
      to compare the output given by human operators against the algorithm. METHODS:
      The identification algorithm detected the beat's onset and end on the basis of
      the maximum rising phase, the choice of possible ventricular systolic starting
      points considering cardiac frequency, and the adjustment of some tolerance values
      to optimize the behavior. Out of 800 patients in the study, 40 occlusive records
      (supradiastolic- subsystolic) were randomly selected without any preliminary
      diagnosis. Radial impedance plethysmographic pulse and standard ECG were recorded
      digitizing and storing the data. Cardiac frequency was estimated with the Power
      Density Function and, thereafter, the signal was derived twice, followed by
      binarization of the first derivative and rectification of the second derivative.
      The product of the two latter results led to a weighing signal from which the
      cycles' onsets and ends were established. Weighed and frequency filters are
      needed along with the pre-establishment of their respective tolerances. Out of
      the 40 records, 30 seconds strands were randomly chosen to be analyzed by the
      algorithm and by two operators. Sensitivity and accuracy were calculated by means
      of the true/false and positive/negative criteria. Synchronization ability was
      measured through the coefficient of variation and the median value of correlation
      for each patient. These parameters were assessed by means of Friedman's ANOVA and
      Kendall Concordance test. RESULTS: Sensitivity was 97% and 91% for the two
      operators, respectively, while accuracy was cero for both of them. The
      synchronism variability analysis was significant (p < 0.01) for the two
      statistics, showing that the algorithm produced the best result. CONCLUSION: The
      proposed algorithm showed good performance as expressed by its high sensitivity.
      The correlation analysis demonstrated that, from the synchronism point of view,
      the algorithm performed the best detection. Patients with marked arrhythmic
      processes are not good candidates for this kind of analysis. At most, they would
      be singled out by the algorithm and, thereafter, to be checked by an operator.

PMID- 16095533
TI  - Stride-to-stride variability while backward counting among healthy young adults.
AB  - BACKGROUND: Little information exists about the involvement of attention in the
      control of gait rhythmicity. Variability of both stride time and stride length is
      closely related to the control of the rhythmic stepping mechanism. We sought 1)
      to determine whether backward counting while walking could provoke significant
      gait changes in mean values and coefficients of variation of stride velocity,
      stride time and stride length among healthy young adults; and 2) to establish
      whether change in stride-to-stride variability could be related to dual-task
      related stride velocity change, attention, or both. METHODS: Mean values and
      coefficients of variation of stride velocity, stride time and stride length were
      recorded using the Physilog-system, at a self-selected walking speed in 49
      healthy young adults (mean age 24.1 +/- 2.8 years, women 49%) while walking alone
      and walking with simultaneous backward counting. Performance on backward counting
      was evaluated by recording the number of figures counted while sitting alone and
      while walking. RESULTS: Compared with walking alone, a significant dual-task
      related decrease was found for the mean values of stride velocity (p < 0.001),
      along with a small but significant increase for the mean values and coefficients
      of variation of stride time (p < 0.001 and p = 0.015, respectively). Stride
      length parameters did not change significantly between both walking conditions.
      Dual-task-related increase of coefficient of variation of stride time was
      explained by changing stride velocity and variability between subjects but not by
      backward counting. The number of figures counted while walking decreased
      significantly compared to backward counting alone. Further, the dual-task related
      decrease of the number of enumerated figures was significantly higher than the
      dual-task related decrease of stride velocity (p = 0.013). CONCLUSION: The
      observed performance-changes in gait and backward counting while dual tasking
      confirm that certain aspects of walking are attention-demanding in young adults.
      In the tested group of 49 young volunteers, dual tasking caused a small decrease
      in stride velocity and a slight increase in the stride-to-stride variability of
      stride time, while stride velocity variability was not affected by the attention
      demanding task. The increase in stride time variability was apparently the result
      of a change in gait speed, but not a result of dual tasking. This suggests that
      young adults require minimal attention for the control of the rhythmic stepping
      mechanism while walking.

PMID- 16095534
TI  - Pretest probability assessment derived from attribute matching.
AB  - BACKGROUND: Pretest probability (PTP) assessment plays a central role in
      diagnosis. This report compares a novel attribute-matching method to generate a
      PTP for acute coronary syndrome (ACS). We compare the new method with a validated
      logistic regression equation (LRE). METHODS: Eight clinical variables
      (attributes) were chosen by classification and regression tree analysis of a
      prospectively collected reference database of 14,796 emergency department (ED)
      patients evaluated for possible ACS. For attribute matching, a computer program
      identifies patients within the database who have the exact profile defined by
      clinician input of the eight attributes. The novel method was compared with the
      LRE for ability to produce PTP estimation <2% in a validation set of 8,120
      patients evaluated for possible ACS and did not have ST segment elevation on ECG.
      1,061 patients were excluded prior to validation analysis because of ST-segment
      elevation (713), missing data (77) or being lost to follow-up (271). RESULTS: In
      the validation set, attribute matching produced 267 unique PTP estimates [median
      PTP value 6%, 1st-3rd quartile 1-10%] compared with the LRE, which produced 96
      unique PTP estimates [median 24%, 1st-3rd quartile 10-30%]. The areas under the
      receiver operating characteristic curves were 0.74 (95% CI 0.65 to 0.82) for the
      attribute matching curve and 0.68 (95% CI 0.62 to 0.77) for LRE. The attribute
      matching system categorized 1,670 (24%, 95% CI = 23-25%) patients as having a PTP
      < 2.0%; 28 developed ACS (1.7% 95% CI = 1.1-2.4%). The LRE categorized 244 (4%,
      95% CI = 3-4%) with PTP < 2.0%; four developed ACS (1.6%, 95% CI = 0.4-4.1%).
      CONCLUSION: Attribute matching estimated a very low PTP for ACS in a
      significantly larger proportion of ED patients compared with a validated LRE.

PMID- 16095536
TI  - The fractal geometry of nutrient exchange surfaces does not provide an
      explanation for 3/4-power metabolic scaling.
AB  - BACKGROUND: A prominent theoretical explanation for 3/4-power allometric scaling
      of metabolism proposes that the nutrient exchange surface of capillaries has
      properties of a space-filling fractal. The theory assumes that nutrient exchange
      surface area has a fractal dimension equal to or greater than 2 and less than or
      equal to 3 and that the volume filled by the exchange surface area has a fractal
      dimension equal to or greater than 3 and less than or equal to 4. RESULTS: It is
      shown that contradicting predictions can be derived from the assumptions of the
      model. When errors in the model are corrected, it is shown to predict that
      metabolic rate is proportional to body mass (proportional scaling). CONCLUSION:
      The presence of space-filling fractal nutrient exchange surfaces does not provide
      a satisfactory explanation for 3/4-power metabolic rate scaling.

PMID- 16095535
TI  - Detection, quantification and genotyping of Herpes Simplex Virus in
      cervicovaginal secretions by real-time PCR: a cross sectional survey.
AB  - BACKGROUND: Herpes Simplex Virus (HSV) Genital Ulcer Disease (GUD) is an
      important public health problem, whose interaction with HIV results in mutually
      enhancing epidemics. Conventional methods for detecting HSV tend to be slow and
      insensitive. We designed a rapid PCR-based assay to quantify and type HSV in
      cervicovaginal lavage (CVL) fluid of subjects attending a Genito-Urinary Medicine
      (GUM) clinic. Vaginal swabs, CVL fluid and venous blood were collected.
      Quantitative detection of HSV was conducted using real time PCR with HSV specific
      primers and SYBR Green I. Fluorogenic TaqMan Minor Groove Binder (MGB) probes
      designed around a single base mismatch in the HSV DNA polymerase I gene were used
      to type HSV in a separate reaction. The Kalon test was used to detect anti-HSV-2
      IgG antibodies in serum. Testing for HIV, other Sexually Transmitted Infections
      (STI) and related infections was based on standard clinical and laboratory
      methods. RESULTS: Seventy consecutive GUM clinic attendees were studied. Twenty
      seven subjects (39%) had detectable HSV DNA in CVL fluid; HSV-2 alone was
      detected in 19 (70%) subjects, HSV-1 alone was detected in 4 (15%) subjects and
      both HSV types were detected in 4 (15%) subjects. Eleven out of 27 subjects (41%)
      with anti-HSV-2 IgG had detectable HSV-2 DNA in CVL fluid. Seven subjects (10%)
      were HIV-positive. Three of seven (43%) HIV-infected subjects and two of five
      subjects with GUD (40%) were secreting HSV-2. None of the subjects in whom HSV-1
      was detected had GUD. CONCLUSION: Quantitative real-time PCR and Taqman MGB
      probes specific for HSV-1 or -2 were used to develop an assay for quantification
      and typing of HSV. The majority of subjects in which HSV was detected had low
      levels of CVL fluid HSV, with no detectable HSV-2 antibodies and were
      asymptomatic.

PMID- 16095537
TI  - Prevalence of ultrasonography proved polycystic ovaries in North Indian women
      with type 2 diabetes mellitus.
AB  - BACKGROUND: Polycystic ovaries (PCO) and their clinical expression (the
      polycystic ovary syndrome [PCOS]) as well as type 2 diabetes mellitus (T2DM) are
      common medical conditions linked through insulin resistance. We studied the
      prevalence of PCO and PCOS in women with diet and/or oral hypoglycemic treated
      T2DM and non-diabetic control women. DESIGN: Prospective study. METHODS: One
      hundred and five reproductive age group women with diet and /or oral hypoglycemic
      treated T2DM were the subjects of the study. Sixty age-matched non-diabetic women
      served as controls. Transabdominal ultrasonographic assessment of the ovaries was
      used to diagnose PCO. Clinical, biochemical and hormonal parameters were also
      noted. RESULTS: Ultrasonographic prevalence of PCO was higher in women with
      diabetes than in non-diabetic subjects (61.0% vs. 36.7%, P < 0.003) whereas that
      of PCOS was 37.1% in diabetic subjects and 25% in non-diabetic controls (P >
      0.1). Diabetic women with PCO had diabetes of significantly longer duration than
      those without PCO (4.19+/-2.0 versus 2.9+/-1.6 yrs; p < 0.05). Among both
      diabetic and non-diabetic women, those with PCO had significantly higher plasma
      LH, LH/FSH ratio, total testosterone and androstenedione levels. CONCLUSION: This
      study demonstrates a higher prevalence of PCO in women with T2DM as compared to
      non-diabetic subjects.

PMID- 16095538
TI  - PALSSE: a program to delineate linear secondary structural elements from protein
      structures.
AB  - BACKGROUND: The majority of residues in protein structures are involved in the
      formation of alpha-helices and beta-strands. These distinctive secondary
      structure patterns can be used to represent a protein for visual inspection and
      in vector-based protein structure comparison. Success of such structural
      comparison methods depends crucially on the accurate identification and
      delineation of secondary structure elements. RESULTS: We have developed a method
      PALSSE (Predictive Assignment of Linear Secondary Structure Elements) that
      delineates secondary structure elements (SSEs) from protein Calpha coordinates
      and specifically addresses the requirements of vector-based protein similarity
      searches. Our program identifies two types of secondary structures: helix and
      beta-strand, typically those that can be well approximated by vectors. In
      contrast to traditional secondary structure algorithms, which identify a
      secondary structure state for every residue in a protein chain, our program
      attributes residues to linear SSEs. Consecutive elements may overlap, thus
      allowing residues located at the overlapping region to have more than one
      secondary structure type. CONCLUSION: PALSSE is predictive in nature and can
      assign about 80% of the protein chain to SSEs as compared to 53% by DSSP and 57%
      by P-SEA. Such a generous assignment ensures almost every residue is part of an
      element and is used in structural comparisons. Our results are in agreement with
      human judgment and DSSP. The method is robust to coordinate errors and can be
      used to define SSEs even in poorly refined and low-resolution structures. The
      program and results are available at http://prodata.swmed.edu/palsse/.

PMID- 16095539
TI  - Allometric scaling of the maximum metabolic rate of mammals: oxygen transport
      from the lungs to the heart is a limiting step.
AB  - BACKGROUND: The maximum metabolic rate (MMR) of mammals is approximately
      proportional to M(0.9), where M is the mammal's body weight. Therefore, MMR
      increases with body weight faster than does the basal metabolic rate (BMR), which
      is approximately proportional to M(0.7). MMR is strongly associated with the
      capacity of the cardiovascular system to deliver blood to capillaries in the
      systemic circulation, but properties of this vascular system have not produced an
      explanation for the scaling of MMR. RESULTS: Here we focus on the pulmonary
      circulation where resistance to blood flow (impedance) places a limit on the rate
      that blood can be pumped through the lungs before pulmonary edema occurs. The
      maximum pressure gradient that does not produce edema determines the maximum rate
      that blood can flow through the pulmonary veins without compromising the
      diffusing capacity of oxygen. We show that modeling the pulmonary venous tree as
      a fractal-like vascular network leads to a scaling equation for maximum cardiac
      output that predicts MMR as a function of M as well as the conventional power
      function aM(b) does and that least-squares regression estimates of the equation's
      slope-determining parameter correspond closely to the value of the parameter
      calculated directly from Murray's law. CONCLUSION: The assumption that cardiac
      output at the MMR is limited by pulmonary capillary pressures that produce edema
      leads to a model that is in agreement with experimental measurements of MMR
      scaling, and the rate of blood flow in pulmonary veins may be rate-limiting for
      the pathway of oxygen.

PMID- 16095540
TI  - Mitral supravalvular ring: a case report.
AB  - Supravalvular mitral stenosis is a rare condition characterized by an abnormal
      ridge, with one or two orifices, covering and obstructing the mitral valve.
      Preoperative diagnosis is difficult with transtoracic echo (TTE), angiography and
      magnetic resonance imaging (MRI). In this case, a 36-year-old male, was admitted
      to our Heart department: He experienced progressive dyspnea on effort and at
      rest. Diagnosis was made by transesophageal echocardiography which showed, on
      apical 4-chamber section, an annular structure attached since a membrane to the
      atrial wall anterior mitral valve leaflet and just proximal to the posterior
      mitral leaflet. Pre-operative identification of the supravalvular mitral ring is
      the target for obtaining good surgical results. Cineangiography and MRI both
      failed in reaching this objective, whereas, transesophageal echocardiography is
      the best method to identify this congenital heart disease. Using TEE the
      identification is not only possible but also easier.

PMID- 16095541
TI  - Inhibition of dynamin-dependent endocytosis increases shedding of the amyloid
      precursor protein ectodomain and reduces generation of amyloid beta protein.
AB  - BACKGROUND: The amyloid precursor protein (APP) is transported via the secretory
      pathway to the cell surface, where it may be cleaved within its ectodomain by
      alpha-secretase, or internalized within clathrin-coated vesicles. An alternative
      proteolytic pathway occurs within the endocytic compartment, where the sequential
      action of beta- and gamma-secretases generates the amyloid beta protein (Abeta).
      In this study, we investigated the effects of modulators of endocytosis on APP
      processing. RESULTS: Human embryonic kidney cells were transfected with a
      dominant negative mutant of dynamin I, an important mediator of clathrin
      dependent endocytosis, and APP proteolysis was analyzed. Overexpression of the
      mutant dynamin (dyn I K44A) resulted in increased shedding of the APP ectodomain
      (sAPPalpha), accumulation of the C-terminal alpha-secretase product C83, and a
      reduction in the release of Abeta. Levels of mature APP on the cell surface were
      increased in cells expressing dyn I K44A, and internalization of surface
      immunolabeled APP, assessed by fluorescence microscopy, was inhibited. Dynamin is
      a substrate for protein kinase C (PKC), and it was hypothesized that activators
      of PKC, which are known to stimulate alpha-secretase-mediated cleavage of APP,
      might exert their effects by inhibiting dynamin-dependent endocytosis. However,
      the internalization of surface-biotinylated APP was unaffected by treatment of
      cells with phorbol 12-myristate 13-acetate in the presence of the alpha-secretase
      inhibitor TAPI-1. CONCLUSION: The results indicate that APP is internalized by a
      dynamin-dependent process, and suggest that alterations in the activity of
      proteins that mediate endocytosis might lead to significant changes in Abeta
      production.

PMID- 16095542
TI  - Low-magnesium, trans-cleavage activity by type III, tertiary stabilized
      hammerhead ribozymes with stem 1 discontinuities.
AB  - BACKGROUND: Low concentrations of free magnesium in the intracellular environment
      can present critical limitations for hammerhead ribozymes, especially for those
      that are designed for intermolecular (trans) cleavage of a host or pathogen RNA.
      Tertiary stabilizing motifs (TSM's) from natural and artificial ribozymes with a
      "type I" topology have been exploited to stabilize trans-cleaving hammerheads.
      Ribozymes with "type II" or "type III" topologies might seem incompatible with
      conversion to trans-cleavage designs, because opening the loop at the end of stem
      1 or stem 2 to accommodate substrate binding is expected to disrupt the TSM and
      eliminate tertiary stabilization. RESULTS: Stem 1, together with single-stranded
      segments capping or internal to this stem, contains both the substrate-binding
      and tertiary stabilization functions. This stem was made discontinuous within the
      sTRSV hammerhead ribozyme, thereby separating the two functions into discrete
      structural segments. The resulting ribozyme, designated "RzC," cleaved its 13
      nucleotide target substrate at MgCl2 concentrations as low as 0.2 mM at 25
      degrees C and 0.5 mM at 37 degrees C. Under multiple-turnover conditions, nearly
      thirty turnovers were observed at the highest substrate:RzC ribozyme ratios.
      Similar stabilization was observed for several derivatives of RzC. Catalytic
      activity was diminished or eliminated at sub-millimolar MgCl2 concentrations for
      ribozymes with weakened or deleted tertiary interactions. Eadie-Hofstee analysis
      revealed that the stabilized and non-stabilized ribozymes bind their substrates
      with equivalent affinities, suggesting that differences in observed activity are
      not the result of diminished binding. Some of the stabilized and non-stabilized
      ribozymes appear to fold into a heterogeneous collection of conformers, only a
      subset of which are catalytically active. CONCLUSION: Hammerhead ribozymes with
      the "type III" topology can be converted to a tertiary, trans-cleavage design.
      Separating the stabilization and substrate recognition functions of stem 1
      increases cleavage activity at physiological concentrations of divalent magnesium
      while retaining recognition of exogenous targets. Trans-cleaving ribozymes that
      exploit the tertiary stabilizing motifs of all natural hammerhead topologies can
      therefore be used in intracellular applications.

PMID- 16095543
TI  - DNA index determination with Automated Cellular Imaging System (ACIS) in
      Barrett's esophagus: comparison with CAS 200.
AB  - BACKGROUND: For solid tumors, image cytometry has been shown to be more sensitive
      for diagnosing DNA content abnormalities (aneuploidy) than flow cytometry. Image
      cytometry has often been performed using the semi-automated CAS 200 system.
      Recently, an Automated Cellular Imaging System (ACIS) was introduced to determine
      DNA content (DNA index), but it has not been validated. METHODS: Using the CAS
      200 system and ACIS, we compared the DNA index (DI) obtained from the same
      archived formalin-fixed and paraffin embedded tissue samples from Barrett's
      esophagus related lesions, including samples with specialized intestinal
      metaplasia without dysplasia, low-grade dysplasia, high-grade dysplasia and
      adenocarcinoma. RESULTS: Although there was a very good correlation between the
      DI values determined by ACIS and CAS 200, the former was 25% more sensitive in
      detecting aneuploidy. ACIS yielded a mean DI value 18% higher than that obtained
      by CAS 200 (p < 0.001; paired t test). In addition, the average time required to
      perform a DNA ploidy analysis was shorter with the ACIS (30-40 min) than with the
      CAS 200 (40-70 min). Results obtained by ACIS gave excellent inter-and intra
      observer variability (coefficient of correlation > 0.9 for both, p < 0.0001).
      CONCLUSION: Compared with the CAS 200, the ACIS is a more sensitive and less time
      consuming technique for determining DNA ploidy. Results obtained by ACIS are also
      highly reproducible.

PMID- 16095545
TI  - Systematic review on urine albumin testing for early detection of diabetic
      complications.
AB  - OBJECTIVES: To determine whether microalbuminuria is an independent prognostic
      factor for the development of diabetic complications and whether improved
      glycaemic or blood pressure control has a greater influence on the development of
      diabetic complications in those with microalbuminuria than in those with
      normoalbuminuria. DATA SOURCES: Electronic databases up until January 2002.
      REVIEW METHODS: A protocol for peer review by an external expert panel was
      prepared that included selection criteria for data extraction and required two
      independent reviewers to undertake article selection and review. Completeness was
      assessed using hand-searching of major journals. Random effects meta-analysis was
      used to obtain combined estimates of relative risk (RR). Funnel plots, trim and
      fill methods and meta-regression were used to assess publication bias and sources
      of heterogeneity. RESULTS: In patients with type 1 or type 2 DM and
      microalbuminuria there is a RR of all-cause mortality of 1.8 [95% confidence
      interval (CI) 1.5 to 2.1] and 1.9 (95% CI 1.7 to 2.1) respectively. Similar RRs
      were found for other mortality end-points, with age of cohort being inversely
      related to the RR in type 2 DM. In patients with type 1 DM, there is evidence
      that microalbuminuria or raised albumin excretion rate has only weak, if any,
      independent prognostic significance for the incidence of retinopathy and no
      evidence that it predicts progression of retinopathy, although strong evidence
      exists for the independent prognostic significance of microalbuminuria or raised
      albumin excretion rate for the development of proliferative retinopathy (crude RR
      of 4.1, 95% CI 1.8 to 9.4). For type 2 DM, there is no evidence of any
      independent prognostic significance for the incidence of retinopathy and little,
      if any, prognostic relationship between microalbuminuria and the progression of
      retinopathy or development of proliferative retinopathy. In patients with type 1
      DM and microalbuminuria there is an RR of developing end-stage renal disease
      (ESRD) of 4.8 (95% CI 3.0 to 7.5) and a higher RR (7.5, 95% CI 5.4 to 10.5) of
      developing clinical proteinuria, with a significantly greater fall in glomerular
      filtration rate (GFR) in patients with microalbuminuria. In patients with type 2
      DM, similar RRs were observed: 3.6 (95% CI 1.6 to 8.4) for developing ESRD and
      7.5 (95% CI 5.2 to 10.9) for developing clinical proteinuria, with a
      significantly greater decline in GFR in the microalbuminuria group of 1.7 (95% CI
      0.1 to 3.2) ml per minute per year compared with those who were normoalbuminuric.
      In adults with type 1 or type 2 DM and microalbuminuria at baseline, the numbers
      progressing to clinical proteinuria (19% and 24%, respectively) and those
      regressing to normoalbuminuria (26% and 18%, respectively) did not differ
      significantly. In children with type 1 DM, regression (44%) was significantly
      more frequent than progression (15%). In patients with type 1 or type 2 DM and
      microalbuminuria, there is scarce evidence as to whether improved glycaemic
      control has any effect on the incidence of cardiovascular disease (CVD), the
      incidence or progression of retinopathy, or the development of renal
      complications. However, among patients not stratified by albuminuria, improved
      glycaemic control benefits retinal and renal complications and may benefit CVD.
      In the effects of angiotensin-converting enzyme (ACE) inhibitors on GFR in
      normotensive microalbuminuric patients with type 1 DM, there was no evidence of a
      consistent treatment effect. There is strong evidence from 11 trials in
      normotensive type 1 patients with microalbuminuria of a beneficial effect of ACE
      inhibitor treatment on the risk of developing clinical proteinuria and on the
      risk of regression to normoalbuminuria. Patients with type 2 DM and
      microalbuminuria, whether hypertensive or not, may obtain additional
      cardiovascular benefit from an ACE inhibitor and there may be a beneficial effect
      on the development of retinopathy in normotensive patients irrespective of
      albuminuria. There is limited evidence that treatment of hypertensive
      microalbuminuric type 2 diabetic patients with blockers of the renin--angiotensin
      system is associated with preserved GFR, but also evidence of no differences in
      GFR in comparisons with other antihypertensive agents. The data on GFR in
      normotensive cohorts are inconclusive. In normotensive type 2 patients with
      microalbuminuria there is evidence from three trials (all enalapril) of a
      reduction in risk of developing clinical proteinuria; in hypertensive patients
      there is evidence from one placebo-controlled trial (irbesartan) of a reduction
      in this risk. Intensive compared with moderate blood pressure control did not
      affect the rate of progression of microalbuminuria to clinical proteinuria in the
      one available study. There is inconclusive evidence from four trials of any
      difference in the proportions of hypertensive patients progressing from
      microalbuminuria to clinical proteinuria when ACE inhibitors are compared with
      other antihypertensive agents, and in one trial regression was two-fold higher
      with lisinopril than with nifedipine. CONCLUSIONS: The most pronounced benefits
      of glycaemic control identified in this review are on retinal and renal
      complications in both normoalbuminuric and microalbuminuric patients considered
      together, with little or no evidence of any greater benefit in those with
      microalbuminuria. Hence, microalbuminuric status may be a false boundary when
      considering the benefits of glycaemic control. Classification of a person as
      normoalbuminuric must not serve to suggest that they will derive less benefit
      from optimal glycaemic control than a person who is microalbuminuric. All
      hypertensive patients benefit from blood pressure lowering and there is little
      evidence of additional benefit in those with microalbuminuria. Antihypertensive
      therapy with an ACE inhibitor in normotensive patients with microalbuminuria is
      beneficial. Monitoring microalbuminuria does not have a proven role in modulating
      antihypertensive therapy while the patient remains hypertensive. Recommendations
      for microalbuminuria research include: determining rate and predictors of
      development and factors involved in regression; carrying out economic evaluations
      of different screening strategies; investigating the effects of screening on
      patients; standardising screening tests to enable use of common reference ranges;
      evaluating the effects of lipid-lowering therapy; and using to modulate
      antihypertensive therapy.

PMID- 16095544
TI  - Transcribed Tc1-like transposons in salmonid fish.
AB  - BACKGROUND: Mobile genetic elements comprise a substantial fraction of vertebrate
      genomes. These genes are considered to be deleterious, and in vertebrates they
      are usually inactive. High throughput sequencing of salmonid fish cDNA libraries
      has revealed a large number of transposons, which remain transcribed despite
      inactivation of translation. This article reports on the structure and potential
      role of these genes. RESULTS: A search of EST showed the ratio of transcribed
      transposons in salmonid fish (i.e., 0.5% of all unique cDNA sequences) to be 2.4
      32 times greater than in other vertebrate species, and 68% of these genes
      belonged to the Tc1-family of DNA transposons. A phylogenetic analysis of reading
      frames indicate repeated transposition of distantly related genes into the fish
      genome over protracted intervals of evolutionary time. Several copies of two new
      DNA transposons were cloned. These copies showed relatively little divergence
      (11.4% and 1.9%). The latter gene was transcribed at a high level in rainbow
      trout tissues, and was present in genomes of many phylogenetically remote fish
      species. A comparison of synonymous and non-synonymous divergence revealed
      remnants of divergent evolution in the younger gene, while the older gene evolved
      in a neutral mode. From a 1.2 MB fragment of genomic DNA, the salmonid genome
      contains approximately 10(5) Tc1-like sequences, the major fraction of which is
      not transcribed. Our microarray studies showed that transcription of rainbow
      trout transposons is activated by external stimuli, such as toxicity, stress and
      bacterial antigens. The expression profiles of Tc1-like transposons gave a strong
      correlation (r2 = 0.63-0.88) with a group of genes implicated in defense
      response, signal transduction and regulation of transcription. CONCLUSION:
      Salmonid genomes contain a large quantity of transcribed mobile genetic elements.
      Divergent or neutral evolution within genomes and lateral transmission can
      account for the diversity and sustained persistence of Tc1-like transposons in
      lower vertebrates. A small part of transposons remain transcribed and their
      transcription is enhanced by responses to acute conditions.

PMID- 16095546
TI  - Randomised controlled trial of the cost-effectiveness of water-based therapy for
      lower limb osteoarthritis.
AB  - OBJECTIVES: To determine the efficacy of community water-based therapy for the
      management of lower limb osteoarthritis (OA) in older patients. DESIGN: A pre
      experimental matched-control study was used to estimate efficacy of water-based
      exercise treatment, to check design assumptions and delivery processes. The main
      study was a randomised controlled trial of the effectiveness of water-based
      exercise (treatment) compared with usual care (control) in older patients with
      hip and/or knee OA. The latter was accompanied by an economic evaluation
      comparing societal costs and consequences of the two treatments. SETTING: Water
      exercise was delivered in public swimming pools in the UK. Physical function
      assessments were carried out in established laboratory settings. PARTICIPANTS:
      106 patients (93 women, 13 men) over the age of 60 years with confirmed hip
      and/or knee OA took part in the preliminary study. A similar, but larger, group
      of 312 patients (196 women, 116 men) took part in the main study, randomised into
      control (159) and water exercise (153) groups. INTERVENTIONS: Control group
      patients received usual care with quarterly semi-structured telephone interview
      follow-up only. The intervention in the main study lasted for 1 year, with a
      further follow-up period of 6 months. MAIN OUTCOME MEASURES: Pain score on the
      Western Ontario and McMaster Universities OA index (WOMAC). Additional outcome
      measures were included to evaluate effects on quality of life, cost-effectiveness
      and physical function measurements. RESULTS: Short-term efficacy of water
      exercise in the management of lower limb OA was confirmed, with effect sizes
      ranging from 0.44 [95% confidence interval (CI) 0.03 to 0.85] on WOMAC pain to
      0.76 (95% CI 0.33 to 1.17) on WOMAC physical function. Of 153 patients randomised
      to treatment, 82 (53.5%) were estimated to have complied satisfactorily with
      their treatment at the 1-year point. This had declined to 28 (18%) by the end of
      the 6-month follow-up period, during which support for the intervention had been
      removed and those wishing to continue exercise had to pay their own costs for
      maintaining their exercise treatment. High levels of co-morbidity were recorded
      in both groups. Nearly two thirds of all patients had a significant other illness
      in addition to their OA. Fifty-four control and 53 exercise patients had hospital
      inpatient episodes during the study period. Water exercise remained effective in
      the main study but overall effect size was small, on WOMAC pain at 1 year, a
      reduction of about 10% in group mean pain score. This had declined, and was non
      significant, at 18 months. Mean cost difference estimates showed a saving in the
      water exercise group of pound123--175 per patient per annum and incremental cost
      effectiveness ratios ranged from pound3838 to pound5951 per quality-adjusted life
      year (QALY). Net reduction in pain was achieved at a net saving of pound135--175
      per patient per annum and the ceiling valuation of pound580--740 per unit of
      WOMAC pain reduction was favourably low. CONCLUSIONS: Group-based exercise in
      water over 1 year can produce significant reduction in pain and improvement in
      physical function in older adults with lower limb OA, and may be a useful adjunct
      in the management of hip and/or knee OA. The water-exercise programme produced a
      favourable cost--benefit outcome, using reduction in WOMAC pain as the measure of
      benefit. Further research is suggested into other similar public health
      interventions. Investigation is also needed into how general practice can best be
      supported to facilitate access to participants for research trials in healthcare,
      as well as an examination of the infrastructure and workforce capacities for
      physical activity delivery and the potential extent to which healthcare may be
      supported in this way. More detailed research is required to develop a better
      understanding of the types of exercise that will work for the different
      biomechanical subtypes of knee and hip OA and investigation is needed on access
      and environmental issues for physical activity programmes for older people, from
      both a provider and a participant perspective, the societal costs of the
      different approaches to the management of OA and longer term trends in outcome
      measures (costs and effects).

PMID- 16095547
TI  - Longer term clinical and economic benefits of offering acupuncture care to
      patients with chronic low back pain.
AB  - OBJECTIVES: To test whether patients with persistent non-specific low back pain,
      when offered access to traditional acupuncture care alongside conventional
      primary care, gained more long-term relief from pain than those offered
      conventional care only, for equal or less cost. Safety and acceptability of
      acupuncture care to patients, and the heterogeneity of outcomes were also tested.
      DESIGN: A pragmatic, two parallel group, randomised controlled trial. Patients in
      the experimental arm were offered the option of referral to the acupuncture
      service comprising six acupuncturists. The control group received usual care from
      their general practitioner (GP). Eligible patients were randomised in a ratio of
      2:1 to the offer of acupuncture to allow between-acupuncturist effects to be
      tested. SETTING: Three non-NHS acupuncture clinics, with referrals from 39 GPs
      working in 16 practices in York, UK. PARTICIPANTS: Patients aged 18-65 years with
      non-specific low back pain of 4-52 weeks' duration, assessed as suitable for
      primary care management by their general practitioner. INTERVENTIONS: The trial
      protocol allowed up to ten individualised acupuncture treatments per patient. The
      acupuncturist determined the content and the number of treatments according to
      patient need. MAIN OUTCOME MEASURES: The Short Form 36 (SF-36) Bodily Pain
      dimension (range 0-100 points), assessed at baseline, and 3, 12 and 24 months.
      The study was powered to detect a 10-point difference between groups at 12 months
      post-randomisation. Cost--utility analysis was conducted at 24 months using the
      EuroQoL 5 Dimensions (EQ-5D) and a preference-based single index measure derived
      from the SF-36 (SF-6D). Secondary outcomes included the McGill Present Pain Index
      (PPI), Oswestry Pain Disability Index (ODI), all other SF-36 dimensions,
      medication use, pain-free months in the past year, worry about back pain,
      satisfaction with care received, and safety and acceptability of acupuncture
      care. RESULTS: A total of 159 patients were in the 'acupuncture offer' arm and 80
      in the 'usual care' arm. All 159 patients randomised to the offer of acupuncture
      care chose to receive acupuncture treatment, and received an average of eight
      acupuncture treatments within the trial. Analysis of covariance, adjusting for
      baseline score, found an intervention effect of 5.6 points on the SF-36 Pain
      dimension [95% confidence interval (CI) -1.3 to 12.5] in favour of the
      acupuncture group at 12 months, and 8 points (95% CI 0.7 to 15.3) at 24 months.
      No evidence of heterogeneity of effect was found for the different
      acupuncturists. Patients receiving acupuncture care did not report any serious or
      life-threatening events. No significant treatment effect was found for any of the
      SF-36 dimensions other than Pain, or for the PPI or the ODI. Patients receiving
      acupuncture care reported a significantly greater reduction in worry about their
      back pain at 12 and 24 months compared with the usual care group. At 24 months,
      the acupuncture care group was significantly more likely to report 12 months pain
      free and less likely to report the use of medication for pain relief. The
      acupuncture service was found to be cost-effective at 24 months; the estimated
      cost per quality-adjusted (QALY) was 4241 pounds sterling (95% CI 191 pounds
      sterling to 28,026 pounds sterling) using the SF-6D scoring algorithm based on
      responses to the SF-36, and 3598 pounds sterling (95% CI 189 pounds sterling to
      22,035 pounds sterling) using the EQ-5D health status instrument. The NHS costs
      were greater in the acupuncture care group than in the usual care group. However,
      the additional resource use was less than the costs of the acupuncture treatment
      itself, suggesting that some usual care resource use was offset. CONCLUSIONS:
      Traditional acupuncture care delivered in a primary care setting was safe and
      acceptable to patients with non-specific low back pain. Acupuncture care and
      usual care were both associated with clinically significant improvement at 12-
      and 24-month follow-up. Acupuncture care was significantly more effective in
      reducing bodily pain than usual care at 24-month follow-up. No benefits relating
      to function or disability were identified. GP referral to a service providing
      traditional acupuncture care offers a cost-effective intervention for reducing
      low back pain over a 2-year period. Further research is needed to examine many
      aspects of this treatment including its impact compared with other possible short
      term packages of care (such as massage, chiropractic or physiotherapy), various
      aspects of cost-effectiveness, value to patients and implementation protocols.

PMID- 16095548
TI  - Cost-effectiveness and safety of epidural steroids in the management of sciatica.
AB  - OBJECTIVES: To investigate the clinical effectiveness of epidural steroid
      injections (ESIs) in the treatment of sciatica with an adequately powered study
      and to identify potential predictors of response to ESIs. Also, to investigate
      the safety and cost-effectiveness of lumbar ESIs in patients with sciatica.
      DESIGN: A pragmatic, prospective, multicentre, double-blind, randomised, placebo
      controlled trial with 12-month follow-up was performed. Patients were stratified
      according to acute (<4 months since onset) versus chronic (4-18 months)
      presentation. All analyses were performed on an intention-to-treat basis with
      last observation carried forward used to impute missing data. SETTING:
      Rheumatology, orthopaedic and pain clinics in four participating centres: three
      district hospitals and one teaching hospital in the south of England.
      PARTICIPANTS: Total of 228 patients listed for ESI with clinically diagnosed
      unilateral sciatica, aged between 18 and 70 years, who had a duration of symptoms
      between 4 weeks and 18 months. INTERVENTIONS: Patients received up to three
      injections of epidural steroid and local anaesthetic (active), or an injection of
      normal saline into the interspinous ligament (placebo). MAIN OUTCOME MEASURES:
      The primary outcome measure was the Oswestry Disability Questionnaire (ODQ);
      measures of pain relief and psychological and physical function were collected.
      Health economic data on return to work, analgesia use and other interventions
      were also measured. Quality-adjusted life-years (QALYs) were calculated using the
      SF-6D, calculated from the Short Form (SF-36). Costs per patient were derived
      from figures supplied by the centres' finance departments and a costings exercise
      performed as part of the study. A cost-utility analysis was performed using the
      SF-36 to calculate costs per QALY. RESULTS: ESI led to a transient benefit in ODQ
      and pain relief, compared with placebo at 3 weeks (p = 0.017, number needed to
      treat = 11.4). There was no benefit over placebo between weeks 6 and 52. Using
      incremental QALYs, this equates to and additional 2.2 days of full health. Acute
      sciatica seemed to respond no differently to chronic sciatica. There were no
      significant differences in any other indices, including objective tests of
      function, return to work or need for surgery at any time-points. There were no
      clinical predictors of response, although the trial lacked sufficient power to be
      confident of this. Adverse events were uncommon, with no difference between
      groups. Costs per QALY to providers under the trial protocol were 44,701 pounds
      sterling. Costs to the purchaser per QALY were 354,171 pounds sterling. If only
      one ESI was provided then costs per QALY fell to 25,745 pounds sterling to the
      provider and 167,145 pounds sterling to the purchaser. ESIs thus failed the QALY
      threshold recommended by the National Institute for Health and Clinical
      Excellence (NICE). CONCLUSIONS: Although ESIs appear relatively safe, it was
      found that they confer only transient benefit in symptoms and self-reported
      function in a small group of patients with sciatica at substantial costs. ESIs do
      not provide good value for money if NICE recommendations are followed. Additional
      research is suggested into the epidemiology of radicular pain, producing a
      register of all ESIs, possible subgroups who may benefit from ESIs, the use of
      radiological imaging, optimal early interventions, analgesic agents and nerve
      root injections, the use of cognitive behavioural therapy in rehabilitation,
      improved methods of assessment, a comparative cost-utility analysis between
      various treatment strategies, and methods to reduce the effect of scarring and
      inflammation.

PMID- 16095549
TI  - Numerosity-duration interference: a Stroop experiment.
AB  - The existence of a possible common mechanism for duration and numerosity
      processing was tested with a Stroop task. Participants had to compare either the
      duration or the numerosity of sequences of flashing dots for which the duration
      and numerosity were independently manipulated to create congruent, incongruent or
      neutral pairs. Results show that the numerical cues interfered with duration
      processing, whereas the temporal cues did not interfere with numerosity
      processing. These findings extend the idea of an automatic access to magnitude to
      non-symbolic sequentially presented material, and reflect a probable difference
      in the mandatory processing of numerosity and duration.

PMID- 16095550
TI  - Reappearance of Anopheles minimus in Singhbum hills of East-Central India.
AB  - Anopheles minimus, an important malaria vector of South East Asia, has reappeared
      in the Singhbum hills, East-Central India where deforestation and DDT residual
      spraying had reportedly eliminated it during the Malaria Eradication Programme.
      The species reported has been identified as sibling species A of the An. minimus
      complex. An. minimus is susceptible to both deltamethrin and DDT. The study shows
      that the environmental conditions in this region still favour the existence of
      the species and one of the possible reasons for its reappearance may be the
      scaling down of residual insecticide spraying in the area.

PMID- 16095551
TI  - Polyethyleneimine as a transmembrane carrier of fluorescently labeled proteins
      and antibodies.
AB  - Polyethyleneimine (PEI) has been used previously as a nonviral DNA transfer
      vector. In this article, we demonstrate its use as a vehicle for transmembrane
      delivery of proteins in cell culture conditions. Linking proteins to PEI required
      no other treatment beyond mixing them with PEI. The bond between PEI and protein
      combined at optimal ratios was maintained in electrophoresis, even in the
      presence of 2.5% sodium dodecyl sulfate (SDS). The optimal time for delivery of
      proteins was determined to be 24 h. We have successfully delivered an Alexa 488
      labeled avidin protein into human glioblastoma cells. A functional antibody
      against the nuclear protein lamin was delivered into human fibroblasts and
      reacted with lamin inside live cells. PEI-based delivery of antibodies and
      fluorescently labeled proteins can be used for fluorescent detection, tracking,
      and evaluation of cellular protein function in vivo.

PMID- 16095552
TI  - Timeliness and task specification in designing for human factors in railway
      operations.
AB  - Human error is often related to flaws in system design which might have been
      avoided had greater attention been paid to human factors knowledge and methods as
      the system was developed. The paper considers the role of human factors in system
      design and argues that adopting an operational perspective in identifying human
      factors issues ensures that subsequent human factors advice is focused upon real
      needs and is consistent with how managers and engineers choose to manage their
      systems. It also considers the issue of timeliness of human factors input.
      Failure to consider human factors issues at a time when other design decisions
      are being taken often means that it is less straightforward to accommodate
      changes. Thus, managers and engineers may resist dealing effectively with
      potential human factors problems for reasons of cost and delay in meeting project
      milestones.

PMID- 16095553
TI  - Cognitive aspects of tool use.
AB  - Tool use has traditionally been viewed as primarily a physical activity, with
      little consideration given to the cognitive aspects that might be involved. In
      this paper, a new approach to considering tool use in terms of Forms of
      Engagement is presented and discussed. This approach combines notions of schema
      from cognitive psychology with the idea of task-specific devices to explain
      psychomotor aspects of using tools. From the perspective of Forms of Engagement,
      various aspects of craftwork and skilled tool use are considered.

PMID- 16095554
TI  - Analysing and modelling train driver performance.
AB  - Arguments for the importance of contextual factors in understanding human
      performance have been made extremely persuasively in the context of the process
      control industries. This paper puts these arguments into the context of the train
      driving task, drawing on an extensive analysis of driver performance with the
      Automatic Warning System (AWS). The paper summarises a number of constructs from
      applied psychological research thought to be important in understanding train
      driver performance. A 'situational model' is offered as a framework for
      investigating driver performance. The model emphasises the importance of
      understanding the state of driver cognition at a specific time ('Now') in a
      specific situation and a specific context.

PMID- 16095555
TI  - Two enzymes, BtaA and BtaB, are sufficient for betaine lipid biosynthesis in
      bacteria.
AB  - Betaine lipids are non-phosphorous glycerolipid analogs of phosphatidylcholine.
      The biosynthesis of the betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine
      has previously been studied in phosphate-starved cells of the purple bacterium
      Rhodobacter sphaeroides, and a genetic approach identified two proteins that are
      necessary for this process. Here, we show that all reactions of DGTS biosynthesis
      in R. sphaeroides are attributable to RsBtaA and RsBtaB, as co-expression of the
      respective genes leads to DGTS formation in Escherichia coli, which normally
      lacks this lipid. The recombinant RsBtaA protein was membrane-associated and
      showed S-adenosylmethionine/diacylglycerol 3-amino-3-carboxypropyl transferase
      activity. RsBtaA directed the transfer of label from 1-[(14)C]S
      adenosylmethionine or [(14)C]diacylglycerol at equal rates into the betaine lipid
      precursor diacylglycerylhomoserine identifying both metabolites as the substrates
      of the reaction. Comparative analysis of RsBtaA and its bacterial orthologs
      revealed a motif with similarity to the AdoMet binding pocket of
      methyltransferases, and allowed the prediction of residues involved in substrate
      binding.

PMID- 16095556
TI  - A radiographic study of tooth development in hypodontia.
AB  - OBJECTIVE: To investigate the radiographic development of permanent teeth in a
      group of children (66 females and 69 males, aged 3.08-15.02 years) with agenesis
      of one or more permanent teeth compared to a matched group. DESIGN: Tooth
      formation of all developing permanent teeth was assessed using Haavikko's method
      (1970) from dental panoramic tomographs. The difference between dental and
      chronological age was tested using a paired t-test. The correlation between the
      difference of dental and chronological age and severity of hypodontia was
      investigated using Spearman correlation test. In addition, radiographs of all
      children with only one single missing tooth in one quadrant and no more than two
      agenesis in total (N=59), were analyzed using the non-parametric Wilcoxon sign
      test, in order to investigate if the development of the teeth adjacent to the
      site of the agenesis was effected. RESULTS: Tooth formation in children with
      hypodontia was significantly delayed compared to the matched group (p<0.001). The
      mean difference was 1.51 years (S.D. 1.37 years). The severity of the hypodontia
      effected the magnitude of the delay (p<0.01). The teeth adjacent to the site of
      the agenesis were significantly delayed compared to the corresponding teeth in
      the matched group (p<0.01). CONCLUSION: These results confirm that the
      development of permanent teeth in children with hypodontia is different when
      compared with a matched group.

PMID- 16095557
TI  - Cloning of hamster osteopontin and expression distribution in normal tissues and
      experimentally induced oral squamous-cell carcinoma.
AB  - Osteopontin (OPN) is a non-collagenous extracellular matrix (ECM) protein
      expressed and secreted by several human cancers. This study investigated the
      expression pattern of OPN during development of oral squamous-cell carcinoma by
      using 7,12-dimethylbenz[a]anthracene (DMBA)-induced squamous-cell carcinomas in
      buccal pouch of syrian golden hamsters. We first identified the hamster OPN cDNA
      sequence by screening of a hamster calvariae cDNA library with a rat OPN cDNA
      probe. The resulting 1,449 bp of hamster OPN cDNA led to a deduced protein
      sequence of 305 amino acids containing several putative binding sites to
      integrins, CD44 receptors, calcium ions and hydroxyapatite, as well as multiple
      sites for phosphorylation, glycosylation and sulphation. Hamster OPN cDNA was
      then used as a probe to analyze the expression of OPN mRNA by Northern blot and
      in situ hybridization analyses of normal and malignant tissues. OPN mRNA was
      detected in several non-mineralized tissues as well as in mineralized tissues,
      but was not present in normal hamster buccal epithelium. DMBA-treated hamster
      buccal pouches expressed OPN mRNA as early as 4 weeks and displayed the highest
      level of expression at 15 weeks. The specimens treated with DMBA for 15 weeks
      exhibited histological features of squamous-cell carcinoma, presented
      microcrystalline deposits and showed OPN expression associated with malignant
      epithelium and tumor-associated macrophages. To summarize, our results suggest
      that buccal-pouch carcinogenesis of Syrian golden hamster may constitute an
      excellent experimental model to study the mechanisms by which OPN is associated
      with oral cancer pathogenesis, and to validate OPN-based therapeutic approaches
      to ameliorate oral cancer progression and metastasis.

PMID- 16095558
TI  - EPR characterisation of the triplet state in photosystem II reaction centers with
      singly reduced primary acceptor Q(A).
AB  - The triplet states of photosystem II core particles from spinach were studied
      using time-resolved cw EPR technique at different reduction states of the iron-
      quinone complex of the reaction center primary electron acceptor. With doubly
      reduced primary acceptor, the well-known photosystem II triplet state
      characterised by zero-field splitting parameters |D|=0.0286 cm(-1), |E|=0.0044
      cm(-1) was detected. When the primary acceptor was singly reduced either
      chemically or photochemically, a triplet state of a different spectral shape was
      observed, bearing the same D and E values and characteristic spin polarization
      pattern arising from RC radical pair recombination. The latter triplet state was
      strongly temperature dependent disappearing at T=100 K, and had a much faster
      decay than the former one. Based on its properties, this triplet state was also
      ascribed to the photosystem II reaction center. A sequence of electron-transfer
      events in the reaction centers is proposed that explains the dependence of the
      triplet state properties on the reduction state of the iron--quinone primary
      acceptor complex.

PMID- 16095559
TI  - Membrane interaction of neuropeptide Y detected by EPR and NMR spectroscopy.
AB  - Neuropeptide Y (NPY) is one of the most abundant peptides in the central nervous
      system of mammals. It belongs to the best-conserved peptides in nature, i.e., the
      amino acid sequences of even evolutionary widely separated species are very
      similar to each other. Using porcine NPY, which differs from human NPY only at
      position 17 (a leucine residue exchanged for a methionine), labeled with a TOAC
      spin probe at the 2nd, 32nd, or 34th positions of the peptide backbone, the
      membrane binding and penetration of NPY was determined using EPR and NMR
      spectroscopy. The vesicular membranes were composed of phosphatidylcholine and
      phosphatidylserine at varying mixing ratios. From the analysis of the EPR line
      shapes, the spectral contributions of free, dimerized, and membrane bound NPY
      could be separated. This analysis was further supported by quenching experiments,
      which selected the contributions of the bound NPY fraction. The results of this
      study give rise to a model where the alpha-helical part of NPY (amino acids 13
      36) penetrates the membrane interface. The unstructured N-terminal part (amino
      acids 1-12) extends into the aqueous phase with occasional contacts with the
      lipid headgroup region. Besides the mixing ratio of zwitterionic and negatively
      charged phospholipid species, the electrostatic peptide membrane interactions are
      influenced by the pH value, which determines the net charge of the peptide
      resulting in a modified membrane binding affinity. The results of these
      variations indicate that NPY binding to phospholipid membranes depends strongly
      on the electrostatic interactions. An estimation of the transfer energy of the
      peptide from aqueous solution to the membrane interface DeltaG supports the
      preferential interaction of NPY with negatively charged membranes.

PMID- 16095560
TI  - Expression of the fetal-oncogenic fibroblast growth factor-8/17/18 subfamily in
      human hematopoietic tumors.
AB  - The fibroblast growth factors (FGFs) are involved in hematopoiesis and
      tumorigenesis. However, little is known about the contribution of the FGFs
      identified within the past 10 years to leukemogenesis. To elucidate whether these
      FGFs (FGF-8, -9, -10, -11, -12, -13, -14, -16, -17, -18, -19, -20, and -21) are
      expressed in leukemic cells, we performed RT-PCR analyses using 28 cell lines.
      The members of a fetal-oncogenic subfamily, FGF-8/-17/-18, were often expressed
      (53.5%, 25.0%, and 32.1%) with the co-expression of their receptors. Realtime
      quantitative-PCR analysis showed that FGF-8/-17 were aberrantly expressed in
      patients with acute leukemia. Moreover, cell proliferation assays revealed the
      proliferation activity of FGF-17 on leukemic cells expressing its receptors.
      These results demonstrated that certain recently identified FGFs play an
      important role in the growth of leukemic cells, possibly with an autocrine mode
      of action, and that these FGFs will become novel biomarkers for hematopoietic
      tumors.

PMID- 16095561
TI  - Extensive variation in the 5'-UTR of Dicer mRNAs influences translational
      efficiency.
AB  - The Dicer enzyme is a key component of the RNA interference pathway and also
      responsible for the processing of micro RNAs, non-coding RNA molecules which
      regulate the activity of mRNAs by antisense base pairing. Little is known about
      the structure and regulation of human Dicer mRNA. A comprehensive
      characterization of Dicer 5'-untranslated region (5'-UTR) RNA structure revealed
      important diversity within human Dicer mRNA transcripts. Three exon 1 variants
      were defined, some of which exhibited very restricted patterns of tissue
      distribution. A number of alternatively spliced 5'-leader exons were also noted,
      revealing the potential for complex post-transcriptional regulation.
      Surprisingly, this diversity all occurred within the 5'-UTR of Dicer mRNAs and
      did not affect the coding region. The Dicer mRNA 5'-UTR variants had profound
      effects on translational efficiency both in vitro and in transiently transfected
      cells. A number of major Dicer RNA species are inefficient substrates for the
      translational machinery.

PMID- 16095562
TI  - Characterization of amino acid variation at strategic positions in parasite and
      human proteases for selective inhibition of falcipains in Plasmodium falciparum.
AB  - Falcipains (FP) of Plasmodium falciparum are important virulence factors marked
      as potential targets for antimalarial drug discovery. In this study, the
      previously uncharacterized fp2B (PF11_0161) was shown to be highly expressed as
      an active enzyme during the erythrocytic stage. With three related proteases in
      the FP family and the existence of human homologues, it is prudent to identify
      clusters of residues unique to the parasite proteases that can be targeted
      selectively for drug design. Using bioinformatic tools, we have carefully mapped
      out a highly conserved and unique region constituted by I85, S149, and A151 in
      the plasmodial proteases that can influence the development of compounds capable
      of inhibiting the entire FP family. Taking drug interactions with the human
      homologues into consideration, these residues in FP2B were replaced with the
      cognate residues found in human cathepsin L (catL) for evaluation. Despite the
      high sequence similarity between the FP2 isozymes (97.5%), FP2B is found to be
      more tolerant to amino acid substitution at position 149 than FP2A. This
      structural disparity implied that residues mediating peptide substrate
      interactions are not fully conserved across the FP family and warrant attention
      in the design and evaluation of protease inhibitors focused on the FPs. The
      simultaneous substitution of the neighboring residues (I85 or A151) rendered the
      double mutants (S149A/I85M and S149A/A151D) completely inactive. Significantly,
      the mutations did not result in 'catL-like' specificity, suggesting that
      substrate-based inhibitors could be rationally designed against these important
      parasite-specific structural determinants.

PMID- 16095563
TI  - Conformational change in full-length mouse prion: a site-directed spin-labeling
      study.
AB  - The structure of the mouse prion (moPrP) was studied using site-directed spin
      labeling electron spin resonance (SDSL-ESR). Since a previous NMR study by
      Hornemanna et al., [Hornemanna, Korthb, Oeschb, Rieka, Widera, Wuthricha,
      Glockshubera, Recombinant full-length murine prion protein, mPrP (23-231):
      purification and spectroscopic characterization, FEBS Lett. 413 (1997) 277-281]
      has indicated that N96, D143, and T189 in moPrP are localized in a Cu(2+) binding
      region, Helix1 and Helix2, respectively, three recombinant moPrP mutations (N96C,
      D143C, and T189C) were expressed in an Escherichia coli system, and then refolded
      by dialysis under low pH and purified by reverse-phase HPLC. By using the
      preparation, we succeeded in preserving a target cystein residue without
      alteration of the alpha-helix structure of moPrP and were able to apply SDSL-ESR
      with a methane thiosulfonate spin label to the full-length prion protein. The
      rotational correlation times (tau) of 1.1, 3.3, and 4.8ns were evaluated from the
      X-band ESR spectra at pH 7.4 and 20 degrees C for N96R1, D143R1, and T189R1,
      respectively. tau reflects the fact that the Cu(2+) binding region is more
      flexible than Helix1 or Helix2. ESR spectra recorded at various temperatures
      revealed two phases together with a transition point at around 20 degrees C in
      D143R1 and T189R1, but not in N96R1. With the variation of pH from 4.0 to 7.8,
      ESR spectra of T189R1 at 20 degrees C showed a gradual increase of tau from 2.9
      to 4.8ns. On the other hand, the pH-dependent conformational changes in N96R1 and
      D143R1 were negligible. These results indicated that T189 located in Helix2
      possessed a structure sensitive to physiological pH changes; simultaneously, N96
      in the Cu(2+) binding region and D143 in Helix1 were conserved.

PMID- 16095564
TI  - Transfer of nitric oxide from nitrovasodilators to free thiols--evidence of two
      distinct stages.
AB  - Two distinct stages, which can be monitored spectrophotometrically, have been
      observed for the first time in multiple reactions between thiol, such as l
      cysteine and some well-known nitrovasodilators, namely S-nitroso-N-acetyl-d,l
      penicillamine (SNAP), S-nitrosoglutathione (GSNO), and S-nitrosocaptopril
      (SNOCap) in aqueous solution (in the presence of EDTA). The first part of the
      reaction occurs at stopped-flow time scale ( approximately 10(-2)s(-1)) in one
      single step and has been found to be transnitrosation; followed by a slow
      decomposition of the products of the transnitrosation reaction with the formation
      of a variety of nitrogen products. Reactivity with regard to the first stage
      occurs in the order GSNO>SNAP>SNOCap. The second stage shows first-order rate
      constants of the order 10(-4)s(-1), although some degree of complexity exists in
      elucidating an accurate rate equation with which a comparative study could be
      done.

PMID- 16095565
TI  - The neuropeptide VIP potentiates IL-6 production induced by proinflammatory
      osteotropic cytokines in calvarial osteoblasts and the osteoblastic cell line
      MC3T3-E1.
AB  - Skeletal turnover is orchestrated by a complex network of regulatory factors.
      Lately, regulation of bone metabolism through neuro-osteological interactions has
      been proposed. Here, we address the question whether IL-6 production can be
      affected by interactions between the neuropeptide VIP and proinflammatory, bone
      resorbing cytokines. By using calvarial osteoblasts, we showed that IL-1beta
      increased IL-6 production time- and concentration-dependently, and that these
      effects were potentiated by VIP. Furthermore, IL-1beta stimulated IL-6 promoter
      activity in the osteoblastic cell line MC3T3-E1 stably transfected with a human
      IL-6 promoter/luciferase construct, and both VIP, and the related neuropeptide
      PACAP-38, increased the effect of IL-1beta in a synergistic manner. The IL-6
      protein release from calvarial osteoblasts was also stimulated by the
      osteoclastogenic, proinflammatory cytokines IL-11, LIF, OSM, IL-17, TGF-beta, and
      TNF-alpha. All effects, except for that of TNF-alpha, were synergistically
      potentiated by VIP. These findings further support the role of neuropeptides, and
      the presence of neuro-immunological interactions, in bone metabolism.

PMID- 16095566
TI  - Platelet adenylyl cyclase activity: a biological marker for major depression and
      recent drug use.
AB  - BACKGROUND: Adenylyl cyclase (AC) is an enzyme that can regulate the physiologic
      effects of numerous drugs and hormones through the production of cyclic adenosine
      3',5'-monophosphate (cAMP). Some studies suggest that certain measures of AC
      activity are lower among depressed subjects. We examined the relationship between
      various measures of AC activity and major depression, taking into account
      potential confounders, such as drug use and gender. METHODS: We assessed the
      relationship between platelet levels of AC activity and lifetime diagnosis of
      major depression among 1481 participants (226 subjects with a history of major
      depression and 1255 control subjects) in an international, cross-sectional study
      initiated by the World Health Organization and the International Society on
      Biomedical Research on Alcoholism. RESULTS: After accounting for recent drug use,
      subjects with a history of major depression had markedly lower mean levels for
      all measures of platelet AC activity compared with control subjects. The adjusted
      odds ratios for major depression comparing the bottom to the top quartile of AC
      activity were 2.69 for basal (95% confidence interval [CI] 1.30-5.56), 3.72 for
      cesium fluoride-stimulated (95% CI 1.54-8.98), 6.20 for forskolin-stimulated (95%
      CI 2.04-18.80), and 2.20 for Gpp(NH)p-stimulated (95% CI 1.03-4.70). CONCLUSIONS:
      Subjects with major depression have lower platelet AC activity levels, and this
      relationship is dramatically attenuated by various types of drug use.

PMID- 16095567
TI  - Neurobiology of decision making: a selective review from a neurocognitive and
      clinical perspective.
AB  - We present a temporal map of key processes that occur during decision making,
      which consists of three stages: 1) formation of preferences among options, 2)
      selection and execution of an action, and 3) experience or evaluation of an
      outcome. This framework can be used to integrate findings of traditional choice
      psychology, neuropsychology, brain lesion studies, and functional neuroimaging.
      Decision making is distributed across various brain centers, which are
      differentially active across these stages of decision making. This approach can
      be used to follow developmental trajectories of the different stages of decision
      making and to identify unique deficits associated with distinct psychiatric
      disorders.

PMID- 16095568
TI  - Cerebral metabolic dysfunction and impaired vigilance in recently abstinent
      methamphetamine abusers.
AB  - BACKGROUND: Methamphetamine (MA) abusers have cognitive deficits, abnormal
      metabolic activity and structural deficits in limbic and paralimbic cortices, and
      reduced hippocampal volume. The links between cognitive impairment and these
      cerebral abnormalities are not established. METHODS: We assessed cerebral glucose
      metabolism with [F-18]fluorodeoxyglucose positron emission tomography in 17
      abstinent (4 to 7 days) methamphetamine users and 16 control subjects performing
      an auditory vigilance task and obtained structural magnetic resonance brain
      scans. Regional brain radioactivity served as a marker for relative glucose
      metabolism. Error rates on the task were related to regional radioactivity and
      hippocampal morphology. RESULTS: Methamphetamine users had higher error rates
      than control subjects on the vigilance task. The groups showed different
      relationships between error rates and relative activity in the anterior and
      middle cingulate gyrus and the insula. Whereas the MA user group showed negative
      correlations involving these regions, the control group showed positive
      correlations involving the cingulate cortex. Across groups, hippocampal metabolic
      and structural measures were negatively correlated with error rates. CONCLUSIONS:
      Dysfunction in the cingulate and insular cortices of recently abstinent MA
      abusers contribute to impaired vigilance and other cognitive functions requiring
      sustained attention. Hippocampal integrity predicts task performance in
      methamphetamine users as well as control subjects.

PMID- 16095569
TI  - Two different putative genetic animal models of childhood depression.
AB  - BACKGROUND: In an attempt to model childhood depression, we examined whether
      existing genetic animal models of depression in adult rats are also valid in
      prepubertal rats. METHODS: Two different "depressed" rat lines were studied: the
      Flinders Sensitive Line (FSL) and their controls, Sprague-Dawley (SD); and the
      Wistar Kyoto (WKY) line and their controls, Wistar. We hypothesized that male
      prepubertal FSL and WKY rats would show increased swim test immobility and
      different patterns of social play and of basal plasma levels of corticosterone
      and adrenocorticotropic hormone (ACTH) compared with control rats. RESULTS:
      Prepubertal FSL and WKY rats exhibited significantly longer duration of
      immobility than control rats in the swim test. The FSL rats demonstrated
      significantly higher levels of social play behaviors and lower levels of
      corticosterone and ACTH compared with SD control rats, whereas WKY rats
      demonstrated significantly lower levels of social play behaviors and higher
      plasma levels of corticosterone and ACTH compared with Wistar control rats.
      CONCLUSIONS: The results might suggest that prepubertal FSL and WKY rats are both
      putative genetic animal models of childhood depression, exhibiting separate
      patterns and symptoms of childhood depression.

PMID- 16095570
TI  - Distinct roles of oxidative stress and antioxidants in the nucleus dorsalis and
      red nucleus following spinal cord hemisection.
AB  - Oxidative stress plays an important role in the pathogenesis of neurodegeneration
      after the acute central nervous system injury. We reported previously that
      increased nitric oxide (NO) production following spinal cord hemisection tends to
      lead to neurodegeneration in neurons of the nucleus dorsalis (ND) that normally
      lacks expression of neuronal NO synthase (nNOS) in opposition to those in the red
      nucleus (RN) that constitutively expresses nNOS. We wondered whether oxidative
      stress could be a mechanism underlying this NO involved neurodegeneration. In the
      present study, we examined oxidative damage evaluated by the presence of 4
      hydroxynonenal (HNE) and iron accumulation and expression of putative antioxidant
      enzymes heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) in neurons of the
      ND and RN after spinal cord hemisection. We found that HNE expression was induced
      in neurons of the ipsilateral ND from 1 to 14 days following spinal cord
      hemisection. Concomitantly, iron staining was seen from 7 to 14 days after
      lesion. HO-1, however, was only transiently induced in ipsilateral ND neurons
      between 3 and 7 days after lesion. In contrast to the ND neurons, HNE was
      undetectable and iron level was unaltered in the RN neurons after spinal cord
      hemisection. HO-1, SOD-Cu/Zn and SOD-Mn were constitutively expressed in RN
      neurons, and lesion to the spinal cord did not change their expression. These
      results suggest that oxidative stress is involved in the degeneration of the
      lesioned ND neurons; whereas constitutive antioxidant enzymes may protect the RN
      neurons from oxidative damage.

PMID- 16095571
TI  - The CRF(1) receptor antagonist, NBI-35965, abolished the activation of locus
      coeruleus neurons induced by colorectal distension and intracisternal CRF in
      rats.
AB  - Corticotropin-releasing factor (CRF) receptors have been reported to play a role
      in tonic colorectal distension (CRD)-induced activation of locus coeruleus (LC)
      neurons. We examined the influence of repeated phasic CRDs and intracisternal
      (ic) CRF on the spontaneous discharge rate of LC neurons in chloral hydrate
      anesthetized rats and the role of CRF receptors using the nonselective
      CRF(1)/CRF(2) antagonist, astressin, and the water-soluble CRF(1) receptor
      antagonist, NBI-35965. Two consecutive phasic CRDs (43.7 +/- 1.1 mm Hg, 30 s
      each) at a 10-min interval increased LC activity to 184.9 +/- 15% and 171.9 +/-
      12.2%, respectively. There was no difference in magnitude, onset (within 1 s),
      and duration (5-7 min) of the LC responses between the 1st and 2nd CRDs. CRF (300
      ng/rat, ic) injected 10 min after the 2nd CRD increased LC activity to 191.1 +/-
      11.2%. Astressin (3 mug, ic) completely blocked the 2nd CRD- and ic CRF-induced
      LC activation. Neither ic vehicle nor astressin influenced basal LC neuronal
      activity. NBI-35965 (10 mg/kg, iv) prevented the 2nd CRD- and ic CRF-induced LC
      neuronal activation, while at 5 mg significantly reduced the LC response to the
      2nd CRD by 80%, but did not block that of ic CRF injected 30 min later. These
      findings indicate a primary role of brain CRF interacting with CRF(1) receptors
      in mediating the activation of LC neurons in response to a phasic CRD within the
      nociceptive range (>40 mm Hg). This activation may have relevance to irritable
      bowel syndrome characterized by lower pain threshold to CRD and hypervigilance to
      colonic input.

PMID- 16095572
TI  - Bacterial lipopolysaccharide (LPS)-induced type 2 iodothyronine deiodinase (D2)
      activation in the mediobasal hypothalamus (MBH) is independent of the LPS-induced
      fall in serum thyroid hormone levels.
AB  - By administration of bacterial lipopolysaccharide (LPS) to intact and T4-replaced
      thyroidectomized rats, we demonstrate that in contrast to the cortex and anterior
      pituitary, there is a persistent increase in type 2 iodothyronine deiodinase (D2)
      activity in the mediobasal hypothalamus (MBH). We propose that endotoxin-induced
      D2 activation in the MBH is independent of circulating levels of thyroid hormone
      and that this mechanism may contribute to central hypothyroidism associated with
      infection.

PMID- 16095573
TI  - The pre-ischaemic neuroprotective effects of N1-dansyl-spermine in a transient
      focal cerebral ischaemia model in mice.
AB  - The pre-ischaemic neuroprotective potential of a novel polyamine/NMDA antagonist
      N1-dansyl-spermine (1-5 mg kg(-1)) was studied in a transient focal cerebral
      ischaemia model in mice in comparison to a reference compound, MK-801 (1 or 3 mg
      kg(-1)). The intraluminal suture transient middle cerebral artery occlusion
      (MCAO) model was used. N1-dansyl-spermine and MK-801 were administered (i.p.) 30
      min prior to ischaemia. A range of histological and behavioural assessments was
      employed. N1-dansyl-spermine had a comparable effect to MK-801 at reducing the
      percentage hemisphere lesion volume (%HLV) at the doses tested. Furthermore, N1
      dansyl-spermine reduced the ischaemic brain oedema, which MK-801 did not. N1
      dansyl-spermine significantly reversed the decrease of locomotor activity (LMA)
      caused by the MCAO and showed a significant effect at improving the rotarod
      performance impaired by MCAO. In contrast, MK-801 had no beneficial effect on
      sensorimotor function and even worsened the LMA. These results clearly
      demonstrate the pre-ischaemic neuroprotective effect of N1-dansyl-spermine in a
      transient focal cerebral ischaemia model.

PMID- 16095574
TI  - Endogenous inhibitors of InsP3-induced Ca2+ release in neuroblastoma cells.
AB  - Cerebellar Purkinje neurons and neuroblastoma N1E-115 cells require 10-50 times
      more InsP3 to induce Ca2+ release than do a variety of non-neuronal cells
      (including astrocytes, hepatocytes, endothelial cells, or smooth muscle cells).
      Given the importance of InsP3-induced Ca2+ release for the development of
      synaptic plasticity in Purkinje neurons, a low InsP3 sensitivity may facilitate
      the integration of numerous synaptic inputs before initiating a change in
      synaptic strength. In the present study, attention is directed at the mechanism
      underlying this low InsP3 sensitivity of Ca2+ release. We show that
      permeabilization of neuroblastoma cells with saponin increased InsP3 sensitivity
      of Ca2+ release, indicating the presence of a diffusible, cytosolic inhibitor(s)
      of Ca2+ release. Consistent with this hypothesis, gel filtration of the
      neuroblastoma cytosol yielded three peaks that inhibited InsP3-induced Ca2+
      release from permeabilized cells. The prominent inhibitory peak decreased the
      InsP3 sensitivity of Ca2+ release from permeabilized cells, did not bind 3H
      InsP3, and was present in sufficient levels to account for the low InsP3
      sensitivity of Ca2+ release in intact neuroblastoma cells. Purification of this
      prominent inhibitory fraction yielded a protein band that was identified by mass
      spectrometry as stress-induced phosphoprotein 1 (mSTI1). Furthermore,
      immunoprecipitation of mSTI1 decreased the inhibitory activity of N1E-115
      cytosol, indicating that mSTI1 contributes to the inhibition of InsP3-induced
      Ca2+ release. Thus, the low InsP3 sensitivity of Ca2+ release in neuroblastoma
      cells can be explained by the presence of cytosolic inhibitors of Ca2+ release
      and include stress-induced phosphoprotein 1.

PMID- 16095575
TI  - Cocaine self-administration and locomotor activity are altered in Lewis and F344
      inbred rats by RTI 336, a 3-phenyltropane analog that binds to the dopamine
      transporter.
AB  - Lewis and Fischer 344 (F344) rats differ in responses to cocaine and
      characteristics of the mesolimbic dopamine system. Compared to F344 rats, Lewis
      rats have lower D2 receptor and dopamine transporter (DAT) levels in nucleus
      accumbens (NAc). We showed previously that altering D1 and D2 receptor levels
      pharmacologically had strain-dependent effects on cocaine self-administration.
      This study tests whether the phenyltropane analog, 3beta-(4-Chlorophenyl) tropane
      2beta-[3-(4'-methylphenyl) isoxazol-5-yl] Hydrochloride (RTI 336), a potent and
      selective DAT inhibitor, differentially alters reinforcing, discriminative, and
      locomotor effects of cocaine in these strains. The effects of RTI 336
      pretreatment on cocaine self-administration were assessed under a fixed-ratio
      (FR) schedule of reinforcement. Its effects on cocaine discrimination were
      conducted using a two-lever food-reinforced task. Finally, the effects of RTI 336
      pretreatment on cocaine-induced locomotor activity were examined. RTI 336
      increased cocaine self-administration in F344 rats, while Lewis rats showed
      reduced intake under the FR schedule. RTI 336 reduced cocaine-induced locomotor
      activity in Lewis rats but not in F344 rats. RTI 336 did not substitute for or
      antagonize cocaine's discriminative stimulus effects in either strain. Results
      show that a DAT inhibitor alters cocaine-induced behaviors in a strain-dependent
      manner. These effects may relate to inherent differences in NAc DAT levels
      between Lewis and F344 rats.

PMID- 16095576
TI  - Phosphorylation of the tau protein sequence 199-205 in the hippocampal CA3 region
      of Syrian hamsters in adulthood and during aging.
AB  - Paired helical filaments formed by the abnormally phosphorylated microtubule
      associated tau are a main sign of Alzheimer's disease and other neurodegenerative
      disorders. The hippocampal CA3 region, a brain region with a high degree of
      synaptic plasticity, is known to be strongly involved in tau hyperphosphorylation
      in several neurodegenerative diseases. In addition, reversible tau
      phosphorylation was observed during hibernation in European ground squirrels. The
      present study provides data on the tau phosphorylation status in the hippocampus
      of euthermic Syrian hamsters (Mesocricetus auratus), laboratory animals
      potentially prone to hibernation. Mossy fibers in the CA3 region of all
      investigated hamsters were immunostained using an antiserum detecting phospho
      serine 199 of tau. A similar staining pattern was obtained with CP-13 detecting
      phospho-serine 202. In contrast, the monoclonal antibody AT8, recognizing both
      phosphorylated serine 202 and threonine 205, stained the CA3 region only in old
      hamsters. These findings implicate an additional link between aging, tau
      phosphorylation and synaptic plasticity. Furthermore, the presented data allow
      analyses whether tau phosphorylation is reversible in these facultative
      hibernators and versatile laboratory animal as it was recently shown for the
      hibernation cycle of European ground squirrels.

PMID- 16095577
TI  - The distal medial perforators of the lower leg and their accompanying veins.
AB  - The skin of the lower leg is nourished by a number of perforating vessels arising
      from the named arteries which travel in the longitudinal axis of the limb. The
      distribution of these perforating arteries has been elucidated using a
      combination of techniques but which are essentially based on cadaveric studies.
      Clinically, this knowledge has provided the basis for methods of local tissue
      transfer in the lower limb. A common finding with the use of local
      fasciocutaneous flaps is venous congestion. The relationship of the veins to the
      arteries in perforating vessels of the lower limb has not been investigated. We
      studied the veins accompanying these arteries by dissecting them in 40 lower
      limbs (20 cadavers). A total of 40 pedicles were dissected. We concentrated our
      analysis of the arterial/venous relationship on the most distal vessels on the
      medial aspect of the lower limbs (the vascular basis for the commonly used
      distally based fasciocutaneous flap). We found that 25 of these arteries were
      accompanied by one perforating vein whereas 12 were accompanied by two or more
      veins. When there was a single vein this was usually larger than the artery in
      external diameter and lay inferior to the artery 76% of the time. When there were
      two veins or more, there was an interconnection between the two around the artery
      in over half of the samples (7/12). Surprisingly, three vessels did not have any
      accompanying vein. This study sheds some light on the variation in venous
      drainage important to the initial survival of these flap transfers.

PMID- 16095578
TI  - The secondary cell wall polymer of Geobacillus tepidamans GS5-97T: structure of
      different glycoforms.
AB  - Nuclear magnetic resonance spectroscopic studies of the strain-specific secondary
      cell wall polymer (SCWP) of the Gram-positive, moderately thermophilic organism
      Geobacillus tepidamans GS5-97T reveal two glycoforms consisting of identical
      tetrasaccharide repeating units with different chemical modifications of the
      amide moieties. On the basis of sugar analyses along with 1D and 2D 1H, 13C, 15N,
      and 31P NMR spectroscopy at natural isotope abundance, the basic backbone
      structure of the SCWP was established to be [beta-D-Manp-2,3-diNAcANH2-(1-->6)
      alpha-D-Glcp-(1-->4)-beta-D-Manp-2,3-diNAcANH2-(1-->3)-alpha-D-GlcpNAc-(1-->]6-(1
      ->O)-PO2-(O-->6)-MurNAc-, with modifications of the amide groups. In one
      glycoform, all beta-D-Manp-2,3-diNAcANH2 (2,3-diacetamido-2,3-dideoxy-beta-D
      mannopyranuronamide, ManpANH2) residues are substituted with two acetyl groups
      (glycoform I) at the amide group at C-6; in the other glycoform (glycoform II),
      only one proton of this amide group is substituted by an acetyl group. The ratio
      between both the glycoforms approximates 1:1.

PMID- 16095579
TI  - Ab initio molecular dynamics simulations of beta-D-glucose and beta-D-xylose
      degradation mechanisms in acidic aqueous solution.
AB  - Ab initio molecular dynamics simulations were employed to investigate, with
      explicit solvent water molecules, beta-D-glucose and beta-D-xylose degradation
      mechanisms in acidic media. The rate-limiting step in sugar degradation was found
      to be protonation of the hydroxyl groups on the sugar ring. We found that the
      structure of water molecules plays a significant role in the acidic sugar
      degradation pathways. Firstly, a water molecule competes with the hydroxyl group
      on the sugar ring for protons. Secondly, water forms hydrogen bonds with the
      hydroxyl groups on the sugar rings, thus weakening the C-C and C-O bonds (each to
      a different degree). Note that the reaction pathways could be altered due to the
      change of relative stability of the C-C and C-O bonds. Thirdly, water molecules
      that are hydrogen-bonded to sugar hydroxyls could easily extract a proton from
      the reaction intermediate, terminating the reaction. Indeed, the sugar
      degradation pathway is complex due to multiple protonation probabilities and the
      surrounding water structure. Our experimental data support multiple sugar acidic
      degradation pathways.

PMID- 16095580
TI  - Extraction of leukemia specific glycan motifs in humans by computational
      glycomics.
AB  - There have been almost no standard methods for conducting computational analyses
      on glycan structures in comparison to DNA and proteins. In this paper, we present
      a novel method for extracting functional motifs from glycan structures using the
      KEGG/GLYCAN database. First, we developed a new similarity measure for comparing
      glycan structures taking into account the characteristic mechanisms of glycan
      biosynthesis, and we tested its ability to classify glycans of different blood
      components in the framework of support vector machines (SVMs). The results show
      that our method can successfully classify glycans from four types of human blood
      components: leukemic cells, erythrocyte, serum, and plasma. Next, we extracted
      characteristic functional motifs of glycans considered to be specific to each
      blood component. We predicted the substructure alpha-D-Neup5Ac-(2-->3)-beta-D
      Galp-(1-->4)-D-GlcpNAc as a leukemia specific glycan motif. Based on the fact
      that the Agrocybe cylindracea galectin (ACG) specifically binds to the same
      substructure, we conducted an experiment using cell agglutination assay and
      confirmed that this fungal lectin specifically recognized human leukemic cells.

PMID- 16095581
TI  - Solid and solution state conformations of (+/-)-3-O-acetyl-1,2:4,5-di-O
      isopropylidene-allo-inositol and (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-6-O
      methyl-allo-inositol.
AB  - The synthesis and conformational studies of (+/-)-3-O-acetyl-1,2:4,5-di-O
      isopropylidene-allo-inositol and (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-6-O
      methyl-allo-inositol are described. Solid state conformations of the title
      compounds have been studied by solving their X-ray crystal structures. The
      inositol ring in both the compounds deviate considerably from the ideal chair
      conformation to flattened chair conformation in the solid state. Their
      conformations in solution were studied by the use of 1H NMR spectroscopy. These
      conformational analyses revealed that the title compounds adopt similar
      conformations in solid and solution states irrespective of the solvent polarity.

PMID- 16095582
TI  - Lack of Delta like 1 and 4 expressions in nude thymus anlages.
AB  - Notch signaling is required for the early steps in T cell development. However,
      distribution of Notch ligands in the thymus anlages is not clear. We investigated
      the expressions of Delta like (Dll) 1 and Dll4 in the mouse thymus anlages. In
      the normal thymus anlages on embryonic day 13, Dll4 is strongly expressed
      throughout the epithelial region, but Dll1 is expressed only in scattered cells.
      In contrast, epithelial cells of the nude thymus anlages express neither Dll1 nor
      Dll4. These results indicate that expressions of Dll1 and Dll4 in thymic
      epithelial cells are regulated by Foxn1 transcriptional factor.

PMID- 16095583
TI  - Mixed monolayers involving DPPC, DODAB and oleic acid and their interaction with
      nicotinic acid at the air-water interface.
AB  - The behaviour of binary mixtures involving dipalmitoylphosphatidylcholine (DPPC),
      dioctadecyldimethylammonium bromide (DODAB) and oleic acid (OA) was investigated
      at the air-water interface by surface pressure-area (pi-A) measurements and by
      Brewster angle microscopy (BAM). Thermodynamic analysis indicates for the system
      DPPC/DODAB miscibility with strong negative deviations from the ideal behaviour,
      from low to high surface pressures over all the composition range. For systems
      DODAB/OA and DPPC/OA, thermodynamic analysis and BAM observation indicate
      miscibility from low to intermediate surface pressures, and phase separation in a
      limited range of composition at high surface pressures. The interaction of
      nicotinic acid (NA) with pure lipids and with selected compositions of mixed
      systems was investigated. Significant positive deviations of pi-A isotherms in
      the presence of NA indicate attractive interactions between NA and the polar
      groups of DPPC and DODAB. NA easily penetrates in expanded regimes while it tends
      to be segregated from condensed regimes in mixed monolayers.

PMID- 16095584
TI  - Membrane permeabilization, orientation, and antimicrobial mechanism of subtilosin
      A.
AB  - Subtilosin A is an antimicrobial peptide produced by the soil bacterium Bacillus
      subtilis that possesses bactericidal activity against a diverse range of
      bacteria, including Listeria monocytogenes. Recent structural studies have found
      that subtilosin A is posttranslationally modified in a unique way, placing it in
      a new class of bacteriocins. In this study, in order to understand the mechanism
      of membrane-disruption by subtilosin A, the interaction of the peptide with model
      phospholipid bilayers is characterized using fluorescence, solid-state NMR and
      differential scanning calorimetry (DSC) experiments. Our results in this study
      show that subtilosin A interacts with the lipid head group region of bilayer
      membranes in a concentration dependent manner. Fluorescence experiments reveal
      the interaction of subtilosin A with small unilamellar vesicles (SUVs) composed
      of POPC, POPG and E. coli total lipids, and that at least one edge of the
      molecule is buried in membrane bilayers. At high concentrations, it induces
      leakage from SUVs of POPC and POPE/POPG (7:3) mixture. (15)N solid-state NMR data
      suggests that the cyclic peptide is partially inserted into bilayers, which is in
      agreement with the fluorescence data. (31)P and (2)H NMR experiments and DSC data
      support the hypothesis that subtilosin A adopts a partially buried orientation in
      lipid bilayers, by showing that it induces a conformational change in the lipid
      headgroup and disordering in the hydrophobic region of bilayers. These results
      suggest that the lipid perturbation observed in this study may be one of the
      consequences of subtilosin A binding to lipid bilayers, which results in membrane
      permeabilization at high peptide concentrations.

PMID- 16095585
TI  - CFSUM1 and CFSUM2 in urine from patients with chronic fatigue syndrome are
      methodological artefacts.
AB  - McGregor et al. reported increased levels of an unidentified urinary compound
      (CFSUM1) in patients with chronic fatigue syndrome (CFS), with reduced excretion
      of another unidentified compound (CFSUM2), and suggested the possibility of
      chemical or metabolic 'markers' for CFS. The identity of CFSUM1 as reported was
      erroneous and the identities of these compounds have remained unknown until now.
      Urine samples were obtained from 30 patients with ME/CFS, 30 age- and sex-matched
      healthy controls, 20 control patients with depression and 22 control patients
      with rheumatoid arthritis. Samples were prepared using the published methods of
      McGregor et al. to produce heptafluorobutyryl-isobutyl derivatives of urinary
      metabolites. Alternative preparations utilised isopropyl, n-butyl and
      trifluoroacetyl derivatives. These were separated and identified using gas
      chromatography-mass spectrometry. CFSUM2 was identified as being partially
      derivatised [isobutyl ester-mono-heptafluorobutyryl (HFB)] serine. CFSUM1 was
      identified as partially derivatised pyroglutamic acid, being the isobutyl ester
      without formation of a HFB derivative. Both CFSUM1 and CFSUM2 are artefacts of
      the sample preparation procedure and previously reported quantitative
      abnormalities of CFSUM1 and CFSUM2 in urine from patients with ME/CFS are also
      artefactual. Pyroglutamic acid may be of primarily dietary origin. The methods
      used cannot provide reliable qualitative or quantitative data on urinary
      metabolites. No clinical or biochemical significance can be drawn between these
      compounds in ME/CFS or any other clinical conditions.

PMID- 16095586
TI  - Resveratrol, a polyphenolic compound in red wine, protects against oxidized LDL
      induced cytotoxicity in endothelial cells.
AB  - BACKGROUND: Resveratrol, a polyphenolic constituent of red wine, has antioxidant
      effects. However, its protective effects against oxLDL-induced endothelial injury
      remained unclarified. METHODS: Primary human umbilical vein endothelial cell
      cultures (HUVECs) treated with oxLDL (200 microg/ml) were used to explore the
      protective effect of resveratrol. Cytotoxicity of oxLDL on HUVECs was studied by
      measuring lactate dehydrogenase (LDH) release, methylthiazol tetrazolium (MTT)
      and apoptotic cell death as characterized by terminal deoxynucleotidyl
      transferase-mediated dUTP nick end-labeling (TUNEL) stain. We also measured the
      production of reactive oxygen species (ROS) by using the fluorescnet probe 2', 7'
      dichlorofluorescein acetoxymethyl ester (DCF-AM), and observed the activity of
      antioxidant enzymes. Furthermore, several apoptotic signaling pathway with
      increased cytosolic calcium, alteration of mitochondrial membrane potential,
      cytochrome c release and activation of caspase 3 were also investigated. RESULTS:
      Resveratrol attenuated oxLDL-induced cytotoxicity, apoptotic features, generation
      of ROS and intracellular calcium accumulation. OxLDL-induced mitochondria
      membrane potential collapase, cytochrome c release and activation of caspase 3 in
      HUVECs were also suppressed by resveratrol pretreatment. CONCLUSIONS: Red wine
      intake may protect against oxLDL-induced dysfunction of endothelial cells.

PMID- 16095587
TI  - Real-time PCR hTERT mRNA pattern in tumor core, edge, resection margin, and lymph
      nodes in laryngeal tumors: relation to proliferative index and impact on
      prognosis.
AB  - BACKGROUND: The immortalizing enzyme, telomerase, has been linked to
      carcinogenesis and is being targeted as a novel molecular marker. This study
      investigated the pattern of human telomerase reverse transcriptase (hTERT) mRNA
      by real-time polymerase chain reaction (PCR) in tumor core, edge, and safety
      margin of laryngeal tumors and related lymph nodes, as well as their relation to
      the proliferative index (PI) and their impact on prognosis. MATERIAL AND METHODS:
      This prospective study included 35 patients with laryngeal carcinoma who were
      surgically treated by total or partial laryngectomy. Collected tissues from tumor
      core, edge, resection margin, and lymph nodes were examined by flow cytometry and
      real-time PCR quantification of hTERT mRNA. RESULTS: The PI showed a
      statistically significant difference between the contrasted parts (P = 0.04). The
      highest median for PI was found in the tumor edge samples (31.3), followed by the
      tumor core (27.5), the resection margin (21.4), and finally the lymph nodes
      (10.3). There was no significant difference with regard to the ploidy patterns or
      the synthetic phase fraction (SPF) among the different tissue parts. Real-time
      PCR hTERT mRNA patterns showed that the highest median for hTERT mRNA level
      (copies/mug RNA) was in the tumor core (70.5), followed by the tumor edge (36.5),
      the resection margin (17.3), and finally the lymph nodes (4.4). There was a
      statistically significant difference with regard to the hTERT mRNA patterns among
      the different tissue parts (P = 0.04). Tumor differentiation, tumor edge ploidy,
      and tumor edge hTERT levels were significantly different between survivors and
      non-survivors, while tumor core S-phase fraction and tumor core PI significantly
      altered the disease-free survival rate. CONCLUSION: hTERT mRNA may potentially be
      used for molecular reevaluation of the safety margin for conservational laryngeal
      surgery, and as a prognostic factor for overall survival especially if determined
      in samples taken from the growing edge of tumors.

PMID- 16095588
TI  - Perceptual learning for speech: Is there a return to normal?
AB  - Recent work on perceptual learning shows that listeners' phonemic representations
      dynamically adjust to reflect the speech they hear (Norris, McQueen, & Cutler,
      2003). We investigate how the perceptual system makes such adjustments, and what
      (if anything) causes the representations to return to their pre-perceptual
      learning settings. Listeners are exposed to a speaker whose pronunciation of a
      particular sound (either /s/ or /integral/) is ambiguous (e.g., halfway between
      /s/ and /integral/). After exposure, participants are tested for perceptual
      learning on two continua that range from /s/ to /integral/, one in the Same voice
      they heard during exposure, and one in a Different voice. To assess how
      representations revert to their prior settings, half of Experiment 1's
      participants were tested immediately after exposure; the other half performed a
      25-min silent intervening task. The perceptual learning effect was actually
      larger after such a delay, indicating that simply allowing time to pass does not
      cause learning to fade. The remaining experiments investigate different ways that
      the system might unlearn a person's pronunciations: listeners hear the Same or a
      Different speaker for 25 min with either: no relevant (i.e., 'good') /s/ or
      /integral/ input (Experiment 2), one of the relevant inputs (Experiment 3), or
      both relevant inputs (Experiment 4). The results support a view of phonemic
      representations as dynamic and flexible, and suggest that they interact with both
      higher- (e.g., lexical) and lower-level (e.g., acoustic) information in important
      ways.

PMID- 16095589
TI  - Improved preservation of human red blood cells by lyophilization.
AB  - The lyophilization of human red blood cells has important implications for blood
      transfusion in clinical medicine. In this study, sugars, human serum albumin,
      polyvinylpyrrolidone, and dimethyl sulfoxide were used as protective reagents for
      the lyophilization of red blood cells. Freezing temperature, shelf temperature,
      and the rehydration conditions were optimized. The results showed that
      extracellular disaccharides, especially trehalose, did not increase the recovery
      of hemoglobin. However, when the concentration of human serum albumin was higher
      than 25%, it had a considerable protective effect on the recovery of lyophilized
      red blood cells; the cellular hemoglobin recovery was over 70%, which was
      significantly higher than that in the group without human serum albumin (P<0.01).
      As the concentration of polyvinylpyrrolidone was increased, the extent of
      vitrification also increased. But when the concentration of polyvinylpyrrolidone
      was over 40%, the resulting concentration of free hemoglobin was over 1g/L, which
      was significantly higher than that with 40% (P<0.01). When lyophilization was
      carried out after freezing at different temperatures, the recovery of cells and
      hemoglobin was 70-80% and there were no significant differences among the five
      groups. When the shelf temperature was higher than -30 degrees C, the samples
      were partly collapsed, but when the shelf temperature was lower than -30 degrees
      C, the recovery of cells in the -40 and -45 degrees C groups was significantly
      higher than in the -30 and -35 degrees C groups (P<0.05). The recovery of cells
      and hemoglobin after lyophilization and rehydration in solutions containing low
      concentrations of polymers was over 80%, which is significantly higher than the
      other groups (P<0.01). In addition, when the temperature was higher than 25
      degrees C, the concentration of free hemoglobin was significantly lower than it
      was at 4 degrees C (P<0.01). In conclusion, our study showed the lyophilization
      of red blood cells is feasible. Disaccharides have no protective effect on
      lyophilized cells when they are only extracellular and extensive vitrification
      may be not beneficial. Although the recovery of cells after lyophilization and
      rehydration by our method was over 70%, the ultrastructure of the cells may be
      compromised and some hemolysis does still exist. Further research is required.

PMID- 16095590
TI  - Peptide YY (3 -36) inhibits dopamine and norepinephrine release in the
      hypothalamus.
AB  - Peptide YY (1-36) and peptide YY (3-36) are gut-derived hormones which are
      involved in feeding control in the hypothalamus. The hypothalamic mechanisms of
      feeding have been shown to be modulated by aminergic neurotransmitters, which
      could mediate the anorectic or orexigenic effects of neuropeptides and hormones.
      We have investigated the role of peptide YY (1-36) and peptide YY (3-36) on
      dopamine, norepinephrine, and serotonin release from hypothalamic synaptosomes in
      vitro. We found that peptide YY (3-36) inhibited depolarization-induced dopamine
      and norepinephrine release, leaving unaffected serotonin release, while peptide
      YY (1-36) did not modify either basal or stimulated amine release. We can
      hypothesize that the effects of peptide YY (3-36) could be mediated by inhibited
      hypothalamic dopamine and norepinephrine release, which could partially account
      for the anorectic activity of the peptide. On the other hand, peptide YY (1-36),
      which has a feeding stimulatory role, does not affect aminergic neurotransmission
      in the hypothalamus.

PMID- 16095591
TI  - A physiological model to study iron recycling in macrophages.
AB  - Following erythrophagocytosis (EP) of senescent red blood cells (RBCs), heme iron
      is recycled to the plasma by tissue macrophages. This process is critical for
      mammalian iron homeostasis but remains elusive. We characterized a cellular model
      using artificially-aged murine RBCs and murine bone marrow-derived macrophages
      (BMDMs) and study mRNA and protein expression of HO-1, ferroportin and ferritin
      after EP. In vitro ageing of RBCs was obtained by raising intracellular calcium
      concentration. These RBCs exhibit several features of erythrocyte senescence
      including externalization of phosphatidyl-serine, specific binding and
      phagocytosis by BMDMs. During the first hours of EP, we observed a rapid increase
      of HO-1 and ferroportin mRNAs and proteins, whereas ferritin protein expression
      was progressively induced with no major changes in RNA levels. At later stages
      after EP, a different pattern of expression was observed with a net decrease of
      ferroportin, a sustained high level of HO-1, and a strong increase in ferritins.
      Taken together, these results suggest that after EP, iron is rapidly extracted
      from heme and exported by ferroportin. Surprisingly, the gene expression profile
      at late stages after EP, which is indicative of iron storage, is reminiscent of
      what is observed in inflammation. However, phagocytosis of artificially-aged red
      blood cells seems to repress the proinflammatory response of macrophages.

PMID- 16095592
TI  - Reversibility of apical dendritic retraction in the rat medial prefrontal cortex
      following repeated stress.
AB  - Apical dendritic retraction and axospinous synapse loss in the medial prefrontal
      cortex (PFC) are structural alterations that result from repeated restraint
      stress. Such changes in this brain region may be associated with impaired working
      memory, altered emotionality, and inability to regulate hypothalamic-pituitary
      adrenal activity, which in turn may underlie stress-related mental illnesses. In
      the present study, we examined the persistence of these stress-induced dendritic
      alterations in the medial PFC following the cessation of stress. Animals received
      either daily restraint stress for a 3-week period and were then allowed to
      recover for another 3 weeks, restraint stress for 3 or 6 weeks, or no restraint.
      Following perfusion and fixation, intracellular iontophoretic injections of
      Lucifer Yellow were performed in layer II/III pyramidal neurons in slices from
      the medial PFC, and apical and basal dendritic arbors were reconstructed in three
      dimensions. We observed a significant reduction in apical dendritic length and
      branch number following 3 or 6 weeks of repeated stress compared to 3-week
      stress/3-week recovery. These results suggest that stress-induced dendritic
      plasticity in the medial PFC is reversible and may have implications for the
      functional recovery of medial PFC function following prolonged psychological
      stress.

PMID- 16095593
TI  - Progesterone restores retrograde labeling of cervical motoneurons in Wobbler
      mouse motoneuron disease.
AB  - The Wobbler mouse, a mutant characterized by motoneuron degeneration in the
      cervical spinal cord, has been used to test the efficacy of novel treatments for
      human motoneuron diseases (HMD). Previous reports have shown that slow axonal
      transport is impaired in Wobblers and other models of HMD. Since progesterone
      (PROG) corrects some morphological, molecular, and functional abnormalities of
      Wobbler mice, we studied if steroid exposure for 8 weeks restored retrograde
      axonal transport by measuring motoneuron labeling after injection of fluorogold
      into the limb muscles. The dye was injected into forelimb biceps bracchii and
      flexor or into the rearlimb gastrocnemius muscles; 6 days later, the number of
      fluorescent motoneurons and the total number of cresyl violet stained motoneurons
      were counted in the cervical (C5-T1) or lumbar (L3-L5) spinal cord regions. A
      pronounced reduction (- 42.2%) of the percent of fluorescent motoneurons in
      Wobbler mice cervical cord was noted, which was significantly corrected after
      PROG treatment. In contrast, labeling of lumbar motoneurons was not reduced in
      Wobbler mice and was not affected by PROG treatment. In no case PROG showed an
      effect in control mice. Concomitantly, PROG slightly but significantly increased
      biceps weight of Wobbler mice. Behaviorally, PROG-treated Wobblers performed
      better on a motor test (hanging time from a horizontal rope) compared to
      untreated counterparts. We postulate a dual role for PROG in the Wobbler mouse,
      in part by prevention of motoneuron degeneration and also by enhancement of
      axonal transport. The latter mechanism could improve the traffic of neurotrophic
      factors from the forelimb muscles into the ailing motoneurons, improving
      neuromuscular function in this murine model of HMD.

PMID- 16095594
TI  - Long-term homocysteine exposure induces alterations in spatial learning,
      hippocampal signalling and synaptic plasticity.
AB  - Abnormally high levels of homocysteine (HCY) have been linked to
      neurodegenerative diseases, but it remains unclear whether this is the cause or
      effect of degenerative processes. Here, we investigated the effects of prolonged
      HCY exposure on cognitive abilities and physiological parameters by injecting
      rats daily with either 20 or 200 mg/kg HCY over a period of up to 14 weeks.
      Notwithstanding a significant weight reduction in the 200 mg HCY group, HCY
      exposed animals did not show a behavioural deficit when tested repeatedly (in
      weeks 1, 3, 5, 7 and 13) in a reference memory version of the water maze.
      Unexpectedly, some improvement in repeated reversal learning was observed in HCY
      exposed animals compared to controls. Pre-treatment with HCY for 3 weeks before
      water maze training did not uncover any cognitive alterations. Increased plasma
      concentrations of HCY were revealed only for the 200 mg HCY group after 14 weeks
      of injections, but no evidence for DNA damage was obtained. Immunocytochemically,
      HCY was detected in the brain after 14 weeks of treatment (both 20 and 200
      mg/kg), but not after 5 weeks. Bidirectional changes in basic synaptic
      transmission and long-term potentiation of hippocampal CA1 pyramidal cells were
      observed at 5, 7 and 14 weeks in both HCY groups, indicative of complex,
      multifactorial time- and concentration-dependent changes. Overall, it is
      concluded that healthy adult rats are able to cope with continuous exposure to
      HCY. While HCY affects growth and neuronal excitability, this does not
      precipitate into an immediate impairment of cognitive function.

PMID- 16095595
TI  - Functional essentiality from topology features in metabolic networks: a case
      study in yeast.
AB  - The relation between the position of mutations in Saccharomyces cerevisiae
      metabolic network and their lethality is the subject of this work. We represent
      the topology of the network by a directed graph: nodes are metabolites and arcs
      represent the reactions; a mutation corresponds to the removal of all the arcs
      referring to the deleted enzyme. Using publicly available knock-out data, we show
      that lethality corresponds to the lack of alternative paths in the perturbed
      network linking the nodes affected by the enzyme deletion. Such feature is at the
      basis of the recently recognized importance of 'marginal' arcs of metabolic
      networks.

PMID- 16095596
TI  - Synthetic studies on heterocyclic natural products.
AB  - This article reviews past and ongoing research in the author's laboratory
      directed toward the synthesis of natural products displaying an azaspirocyclic
      framework, or incorporating a medium-ring nitrogen heterocycle. New synthetic
      technologies were devised in order to address the synthetic problems posed by the
      target molecules. Thus, efforts in the area of azaspirocyclic substances have
      relied on an oxidative amidation of phenols promoted by iodobenzene diacetate,
      whereas access to medium-ring nitrogen heterocycles has been secured by means of
      a ring expansion sequence that relies on the fragmentation of an aziridine
      triggered by a homo-Brook transposition. Details of the development of these
      technologies are presented, together with applications to the total synthesis of
      FR-901483, TAN-1251C, cylindricines, and mitomycinoids.

PMID- 16095597
TI  - Medroxyprogesterone acetate acutely facilitates and sequentially inhibits sexual
      behavior in female rats.
AB  - Medroxyprogesterone acetate (MPA), a synthetic progestin commonly used in
      contraception and hormone replacement therapy, appears to inhibit libido in
      women, but little is known about the mechanisms through which it may exert this
      effect. We compared the acute and sequential actions of MPA and natural
      progesterone (P4) on sexual behavior in female rats to test the hypothesis that
      MPA inhibits sexual behavior, at least in part, by acting as a potent
      progesterone receptor (PR) agonist. Ovariectomized females were placed in one of
      three dose groups (high, mid, or low), and each subject was tested under three
      different conditions (MPA, P4, and vehicle). The order of progestin treatment was
      balanced among subjects, and within each dose group equimolar quantities of MPA
      and P4 were administered. During each trial, females were injected with estradiol
      benzoate (EB, 4 mug) followed by one of three progestin treatments (MPA, P4, or
      vehicle) at +44 h, and behavioral testing at +48 h. On the next day, all females
      were given a standard 500-microg injection of P4 at +68 h and were tested again
      for sexual behavior at +72 h. On the first day of behavioral testing, both MPA
      and P4 induced a pronounced rise in receptive and proceptive behavior at the mid
      and high doses, but at the lowest dose MPA had a much greater effect in
      comparison to P4. On the second day of behavioral testing, MPA attenuated the
      expression of proceptive and receptive behavior at both the mid and high doses,
      whereas P4 only attenuated the expression of lordosis and only did so at the
      highest dose. These findings illustrate that MPA and P4 have a similar impact on
      sexual behavior in female rats and suggest that the inhibitory effects of MPA may
      be attributable, at least in part, to its potent effects at the progesterone
      receptor.

PMID- 16095599
TI  - Effects of Vitamin D analogs on gene expression profiling in human coronary
      artery smooth muscle cells.
AB  - Vitamin D analogs provide survival benefit for chronic kidney disease patients
      with cardiovascular complications. Activation of smooth muscle cells plays a role
      in cardiovascular diseases. It is not known how Vitamin D analogs modulate gene
      expression in smooth muscle cells. In this study, DNA microarray technology was
      used to assess the gene expression profile in human coronary artery smooth muscle
      cells treated with 0.1microM 1alpha,25-dihydroxyvitamin D3 (calcitriol) or
      paricalcitol (an analog of calcitriol) for 30 h. The effects of calcitriol and
      paricalcitol were similar. A total of 176 target genes were identified with 115
      up-regulated and 61 down-regulated genes in the paricalcitol group. Target genes
      fall into various categories including cell differentiation/proliferation. Real
      time RT-PCR analysis demonstrated that paricalcitol dose- and time-dependently
      regulated the expression of IGF1, WT1 and TGFbeta3, three genes known to modulate
      cell proliferation. Paricalcitol also down-regulated the expression of
      natriuretic peptide precursor B and thrombospondin 1. Both drugs inhibited cell
      proliferation in a dose-dependent manner. This study identified genes not
      previously known to be regulated by VDR, providing insight into understanding the
      role of VDR on regulating smooth muscle cell growth, thrombogenicity,
      fibrinolysis and endothelial regeneration.

PMID- 16095600
TI  - The effect of chronic consumption of red wine on cardiovascular disease risk
      factors in postmenopausal women.
AB  - BACKGROUND: Moderate red wine has been shown to reduce cardiovascular disease
      (CVD) risk, however the effects on certain CVD risk factors are unclear. In this
      study we have investigated the effects of dealcoholised red wine (DRW) and full
      complement red wine (RW) on several cardiovascular risk factors in mildly
      hypercholesterolaemic postmenopausal women. OBJECTIVES: To elucidate whether the
      chronic consumption of red wine polyphenols improves risk factors associated with
      CVD in hypercholesterolaemic postmenopausal women. DESIGN: Forty-five
      hypercholesterolaemic postmenopausal women were randomly assigned to consume 400
      mL/day of either water, DRW or RW for 6 weeks following a 4-week washout. Fasting
      measures of lipids, lipoproteins, insulin and glucose were taken at 0 and 6
      weeks. RESULTS: DRW consumption had no effect of fasting concentrations of
      lipids, lipoproteins, insulin and glucose. However, chronic consumption of RW
      significantly reduced fasting LDL cholesterol concentrations by 8% and increased
      HDL cholesterol concentrations by 17% in hypercholesterolaemic postmenopausal
      women. CONCLUSIONS: Collectively, regular consumption of full-complement red wine
      reduces CVD risk by improving fasting lipid levels in hypercholesterolaemic
      postmenopausal women. This study uniquely demonstrated the LDL cholesterol
      lowering effects of red wine in individuals at high CVD risk, which has not
      previously been shown.

PMID- 16095601
TI  - Computational modeling of multicellular constructs with the material point
      method.
AB  - Computational modeling of the mechanics of cells and multicellular constructs
      with standard numerical discretization techniques such as the finite element (FE)
      method is complicated by the complex geometry, material properties and boundary
      conditions that are associated with such systems. The objectives of this research
      were to apply the material point method (MPM), a meshless method, to the modeling
      of vascularized constructs by adapting the algorithm to accurately handle quasi
      static, large deformation mechanics, and to apply the modified MPM algorithm to
      large-scale simulations using a discretization that was obtained directly from
      volumetric confocal image data. The standard implicit time integration algorithm
      for MPM was modified to allow the background computational grid to remain fixed
      with respect to the spatial distribution of material points during the analysis.
      This algorithm was used to simulate the 3D mechanics of a vascularized scaffold
      under tension, consisting of growing microvascular fragments embedded in a
      collagen gel, by discretizing the construct with over 13.6 million material
      points. Baseline 3D simulations demonstrated that the modified MPM algorithm was
      both more accurate and more robust than the standard MPM algorithm. Scaling
      studies demonstrated the ability of the parallel code to scale to 200 processors.
      Optimal discretization was established for the simulations of the mechanics of
      vascularized scaffolds by examining stress distributions and reaction forces.
      Sensitivity studies demonstrated that the reaction force during simulated
      extension was highly sensitive to the modulus of the microvessels, despite the
      fact that they comprised only 10.4% of the volume of the total sample. In
      contrast, the reaction force was relatively insensitive to the effective
      Poisson's ratio of the entire sample. These results suggest that the MPM
      simulations could form the basis for estimating the modulus of the embedded
      microvessels through a parameter estimation scheme. Because of the generality and
      robustness of the modified MPM algorithm, the relative ease of generating spatial
      discretizations from volumetric image data, and the ability of the parallel
      computational implementation to scale to large processor counts, it is
      anticipated that this modeling approach may be extended to many other
      applications, including the analysis of other multicellular constructs and
      investigations of cell mechanics.

PMID- 16095602
TI  - Adsorption of some bivalent heavy metal ions from aqueous solutions by manganese
      nodule leached residues.
AB  - The leached residue, generated after selective extraction of Cu, Ni, and Co in
      sulfur dioxide-ammonia leaching of manganese nodules, was characterized and batch
      isothermal adsorption experiments were conducted at ambient temperature to
      evaluate the effectiveness of the water-washed leached residue for removal of
      different bivalent metal ions from aqueous synthetic solutions. The effects of
      pH, initial metal ion concentrations, amount of adsorbent, interfering ions, and
      heat treatment were also investigated. The uptake of metal ions increased with
      increasing pH. Under identical conditions the adsorption capacity increased in
      the order Cd(2+)<Cu(2+)<Pb(2+). The adsorption kinetics was found to follow a
      first-order rate expression and the experimental equilibrium adsorption data
      fitted reasonably well to both Langmuir and Freundlich isotherm models. Various
      metal ions present in the leached residue were found to be released during
      adsorption of heavy metals, which decreased with increased pH and were
      practically negligible at pH approximately 6.0. Desorption of adsorbed metal ions
      from metal-loaded leached residue and its regeneration ability were also studied.
      The results obtained could be useful for considering the leached manganese
      nodules residue as adsorbent for removal of heavy metal ions from contaminated
      water bodies.

PMID- 16095603
TI  - Assembly of a model hydrophobic drug into cationic bilayer fragments.
AB  - Our previous work has shown that dioctadecyldimethylammonium bromide (DODAB)
      bilayer fragments (BF) presented antimicrobial activity, solubilized fungicides,
      e.g., amphotericin B and miconazole (MCZ), stabilized hydrophobic drug particles
      and were effective in vivo. Here, the interaction between MCZ and DODAB BF is
      evaluated from determination of BF loading capacity and effects of drug-to-lipid
      molar proportion (MP) on particle size, zeta potential and gel-to-liquid
      crystalline phase transition T(m). DODAB BF solubilized MCZ over a range of MP.
      BF loading capacity was 0.5 mM MCZ at 5 mM DODAB. Above this limit, the drug
      aggregated in the dispersion. At pH 6.3, BF zeta potentials decreased with MP,
      suggesting insertion of deprotonated drug into the bilayer. MCZ optical spectra
      in BF were similar to those in best organic solvent, confirming drug
      solubilization. At MP 1:10, BF T(m) remained unchanged, suggesting drug capture
      at BF hydrophobic edges. At MP 1:10, T(m) decreased, showing MCZ insertion into
      DODAB bilayer. However, drug was expelled from the bilayer core upon lowering
      temperature. Minimal fungicidal concentrations against C. albicans were
      synergically reduced by 10 times for drug/BF.

PMID- 16095604
TI  - Phonological recoding and rapid orthographic learning in third-graders' silent
      reading: a critical test of the self-teaching hypothesis.
AB  - This study examined rapid orthographic learning following silent reading in third
      grade children as a function of number of target nonword repetitions and test
      delay. In each of two test sessions at least 6 days apart, children read a series
      of short stories, with each story containing a different nonword repeated either
      four or eight times. In the second session, after the stories had been read,
      children were asked to read short lists of target nonwords or homophonic
      alternatives. Children read target nonwords faster than homophones, indicating
      that they had formed functional orthographic representations of the target
      nonwords through phonologically recoding them during silent story reading. They
      also preferred target nonwords to homophones in an orthographic choice task in
      which the alternatives included the target, the homophone, and a visually similar
      foil, although here orthographic learning was stronger for items encountered
      eight times within stories and stronger for items tested immediately. These
      findings provide critical evidence in support of Share's self-teaching through
      phonological recoding hypothesis.

PMID- 16095605
TI  - Oxygen partial pressure effects on metabolic rate and behavior of tethered flying
      locusts.
AB  - Resting insects are extremely tolerant of hypoxia. However, oxygen requirements
      increase dramatically during flight. Does the critical atmospheric P (O)(2)
      (P(c)) increase strongly during flight, or does increased tracheal conductance
      allow even flying insects to possess large safety margins for oxygen delivery? We
      tested the effect of P(O)(2) on resting and flying CO(2) emission, as well as on
      flight behavior and vertical force production in flying locusts, Schistocerca
      americana. The P(c) for CO(2) emission of resting animals was less than 1 kPa,
      similar to prior studies. The P(c) for flight bout duration was between 10 and 21
      kPa, the P(c) for vertical force production was between 3 and 5 kPa, and the P(c)
      for CO(2) emission was between 10 and 21 kPa. Our study suggests that the P(c)
      for steady-state oxygen consumption is between 10 and 21 kPa (much higher than
      for resting animals), and that tracheal oxygen stores allowed brief flights in 5
      and 10 kPa P(O)(2) atmospheres to occur. Thus, P(c) values strongly increased
      during flight, consistent with the hypothesis that the excess oxygen delivery
      capacity observed in resting insects is substantially reduced during flight.

PMID- 16095606
TI  - Site-saturation mutagenesis is more efficient than DNA shuffling for the directed
      evolution of beta-fucosidase from beta-galactosidase.
AB  - Protein engineers use a variety of mutagenic strategies to adapt enzymes to novel
      substrates. Directed evolution techniques (random mutagenesis and high-throughput
      screening) offer a systematic approach to the management of protein complexity.
      This sub-discipline was galvanized by the invention of DNA shuffling, a procedure
      that randomly recombines point mutations in vitro. In one influential study,
      Escherichia coli beta-galactosidase (BGAL) variants with enhanced beta-fucosidase
      activity (tenfold increase in k(cat)/K(M) in reactions with the novel para
      nitrophenyl-beta-d-fucopyranoside substrate; 39-fold decrease in reactivity with
      the "native"para-nitrophenyl-beta-d-galactopyranoside substrate) were evolved in
      seven rounds of DNA shuffling and screening. Here, we show that a single round of
      site-saturation mutagenesis and screening enabled the identification of beta
      fucosidases that are significantly more active (180-fold increase in k(cat)/K(M)
      in reactions with the novel substrate) and specific (700,000-fold inversion of
      specificity) than the best variants in the previous study. Site-saturation
      mutagenesis thus proved faster, less resource-intensive and more effective than
      DNA shuffling for this particular evolutionary pathway.

PMID- 16095607
TI  - Site-specific dimensions across a highly denatured protein; a single molecule
      study.
AB  - Do highly denatured proteins adopt random coil configurations? Here, we address
      this question by measuring residue-to-residue separations across the denatured
      FynSH3 domain. Using single-molecule Forster resonance energy transfer
      techniques, we have collected transfer efficiency probability distributions for
      dye-labeled, denatured protein. Applying maximum likelihood analysis to the
      interpretation of these distributions, we have determined the through-space
      distance between five residue pairs in the protein's guanidine hydrochloride
      unfolded and trifluoroethanol-unfolded states. We find that, while the dimensions
      of the guanidine hydrochloride -unfolded molecule generally coincide with the
      dimensions predicted for a random coil ensemble, potentially statistically
      significant deviations from random coil behavior are also evident. These small,
      site-specific deviations may provide a means of reconciling earlier, scattering
      based evidence for the random coil nature of the unfolded state with more site
      specific spectroscopic evidence suggesting residual structure. We have also
      studied the unfolded ensemble populated in 50% trifluoroethanol, a denaturant
      that induces a highly helical unfolded state. We find that the size and shape of
      the unfolded ensemble under these conditions is effectively indistinguishable
      from that populated in guanidinium hydrochloride solutions, suggesting that the
      gross structure of the denatured state is, perhaps surprisingly, independent of
      the chemistry of the cosolvent.

PMID- 16095608
TI  - Identification of a universal VHH framework to graft non-canonical antigen
      binding loops of camel single-domain antibodies.
AB  - Camel single-domain antibody fragments (VHHs) are promising tools in numerous
      biotechnological and medical applications. However, some conditions under which
      antibodies are used are so demanding that they can be met by only the most robust
      VHHs. A universal framework offering the required properties for use in various
      applications (e.g. as intrabody, as probe in biosensors or on micro-arrays) is
      highly valuable and might be further implemented when employment of VHHs in human
      therapy is envisaged. We identified the VHH framework of cAbBCII10 as a potential
      candidate, useful for the exchange of antigen specificities by complementarity
      determining region (CDR) grafting. Due to the large number of CDR-H loop
      structures present on VHHs, this grafting technique was expected to be rather
      unpredictable. Nonetheless, the plasticity of the cAbBCII10 framework allows
      successful transfer of antigen specificity from donor VHHs onto its scaffold. The
      cAbBCII10 was chosen essentially for its high level of stability (47 kJmol(-1)),
      good expression level (5 mgl(-1) in E.coli) and its ability to be functional in
      the absence of the conserved disulfide bond. All five chimeras generated by
      grafting CDR-Hs, from donor VHHs belonging to subfamily 2 that encompass 75% of
      all antigen-specific VHHs, on the framework of cAbBCII10 were functional and
      generally had an increased thermodynamic stability. The grafting of CDR-H loops
      from VHHs belonging to other subfamilies resulted in chimeras of reduced antigen
      binding capacity.

PMID- 16095609
TI  - Experimental characterization of the folding kinetics of the notch ankyrin
      domain.
AB  - Proteins constructed from linear arrays of tandem repeats provide a simplified
      architecture for understanding protein folding. Here, we examine the folding
      kinetics of the ankyrin repeat domain from the Drosophila Notch receptor, which
      consists of six folded ankyrin modules and a seventh partly disordered N-terminal
      ankyrin repeat sequence. Both the refolding and unfolding kinetics are best
      described as a sum of two exponential phases. The slow, minor refolding phase is
      limited by prolyl isomerization in the denatured state (D). The minor unfolding
      phase, which appears as a lag during fluorescence-detected unfolding, is
      consistent with an on-pathway intermediate (I). This intermediate, although not
      directly detected during refolding, is shown to be populated by interrupted
      refolding experiments. When plotted against urea, the rate constants for the
      major unfolding and refolding phases define a single non-linear v-shaped chevron,
      as does the minor unfolding phase. These two chevrons, along with unfolding
      amplitudes, are well-fitted by a sequential three-state model, which yields rate
      constants for the individual steps in folding and unfolding. Based on these
      fitted parameters, the D to I step is rate-limiting, and closely matches the
      major observed refolding phase at low denaturant concentrations. I appears to be
      midway between N and D in folding free energy and denaturant sensitivity, but has
      Trp fluorescence properties close to N. Although the Notch ankyrin domain has a
      simple architecture, folding is slow, with the limiting refolding rate constant
      as much as seven orders of magnitude smaller than expected from topological
      predictions.

PMID- 16095610
TI  - Genome-wide survey of prokaryotic O-protein phosphatases.
AB  - Complex and diverse signal transduction circuits are responsible for the
      efficient functioning of cellular network. Protein kinases and O-protein
      phosphatases are primarily responsible for propagating such stimuli within a
      eukaryotic cell. However, there is limited understanding of O-protein
      phosphatases in the prokaryotic genomes. The availability of complete genome
      sequence information for several prokaryotes permits a genome-wide survey of O
      protein phosphatases. The distribution of the various protein phosphatase
      families has been observed to be mosaic, with the exception of the members of the
      phospho protein family P (PPP), which is consistent with previous studies. The
      PPP family is ubiquitous in the prokaryotic world and undergoes the highest
      sequence divergence within a genome amongst phosphatases studied. The co
      occurrence of low molecular mass tyrosine phosphatase (LMWPc) and PPP domain in a
      single polypeptide suggests that the protein present in Archaeoglobus fulgidus
      might represent the progenitor for all protein phosphatases. The curation of data
      on prokaryotic protein phosphatases provides a convenient framework for the
      analysis of domain architectures and for characterising structural and functional
      properties of this important family of signalling proteins.

PMID- 16095611
TI  - Deletion of EFL1 results in heterogeneity of the 60 S GTPase-associated rRNA
      conformation.
AB  - Previous work suggested that the release of the nucleolar Tif6 from nascent 60 S
      subunits occurs in the cytoplasm and requires the cytoplasmic EF-2-like GTPase,
      Efl1. To check whether this release involves an rRNA structural rearrangement
      mediated by Efl1, we analyzed the rRNA conformation of the GTPase center of 80 S
      ribosomes in three contexts: wild-type, Deltaefl1 and a dominant suppressor R1 of
      Deltaefl1. This analysis was restricted to domain II and VI of 25 S rRNA. The
      rRNA analysis of R1 ribosomes allows us to distinguish the effects due to
      depletion of Efl1 from the resulting nucleolar deficit of Tif6. Efl1 inhibits the
      EF-2 GTPase activity, suggesting that the two proteins share a similar ribosome
      binding site. The 80 S ribosomes from either type failed to show any difference
      of conformation in the two rRNA domains analyzed. However, the same analysis
      performed on the pool of free 60 S subunits reveals several rRNA conformational
      differences between wild-type and Deltaefl1 subunits, whereas that from the
      suppressor strain is similar to wild-type. This suggests that the nucleolar
      deficit of Tif6 during assembly of the 60 S preribosomes is responsible for the
      changes in rRNA conformation observed in Deltaefl1 60 S subunits. We also
      purified 60 S preribosomes from the three genetic contexts by TAP-tagging Tif6.
      The protein content of 60 S preribosomes associated with Tif6p in a Deltaefl1
      strain are obtained at a lower yield but have, surprisingly, a protein
      composition that is a priori similar to that of wild-type and the suppressor
      strain.

PMID- 16095612
TI  - Folding cooperativity in a three-stranded beta-sheet model.
AB  - The thermodynamic behavior of a previously designed three-stranded beta-sheet was
      studied via several microseconds of standard and replica exchange molecular
      dynamics simulations. The system is shown to populate at least four thermodynamic
      minima, including two partially folded states in which only a single hairpin is
      formed. Simulated melting curves show different profiles for the C and N-terminal
      hairpins, consistent with differences in secondary structure content in published
      NMR and CD/FTIR measurements, which probed different regions of the chain.
      Individual beta-hairpins that comprise the three-stranded beta-sheet are observed
      to form cooperatively. Partial folding cooperativity between the component
      hairpins is observed, and good agreement between calculated and experimental
      values quantifying this cooperativity is obtained when similar analysis
      techniques are used. However, the structural detail in the ensemble of
      conformations sampled in the simulations permits a more direct analysis of this
      cooperativity than has been performed on the basis of experimental data. The
      results indicate the actual folding cooperativity perpendicular to strand
      direction is significantly larger than the lower bound obtained previously.

PMID- 16095613
TI  - Site-directed mutagenesis of the greasy slide aromatic residues within the LamB
      (maltoporin) channel of Escherichia coli: effect on ion and maltopentaose
      transport.
AB  - The 3D-structure of the maltooligosaccharide-specific LamB-channel of Escherichia
      coli (also called maltoporin) is known from X-ray crystallography. The 3D
      structure suggests that a number of aromatic residues (Y6, Y41, W74, F229, W358
      and W420) within the channel lumen are involved in carbohydrate and ion
      transport. All aromatic residues were replaced by alanine-scanning mutagenesis.
      Furthermore, LamB mutants were created in which two, three, four, five and all
      six aromatic residues were replaced to study their effects on ion and
      maltopentaose transport through LamB. The purified mutant proteins were
      reconstituted into lipid bilayer membranes and the single-channel conductance of
      the mutants was studied in conductance experiments. The results suggest that all
      aromatic residues provide some steric hindrance for ion transport through LamB.
      Highest impact is provided by Y6 and Y41 that are localized opposite Y118, which
      form the central constriction of the LamB channel. Stability constants for
      binding of maltopentaose to the mutant channels were measured using titration
      experiments with the carbohydrate. The mutation of one or several aromatic
      residue(s) led to a substantial decrease of the stability constant of binding.
      The highest effect was observed when all aromatic residues were replaced by
      alanine because no binding of maltopentaose could be detected in such a case.
      However, binding was again possible when Y118 was replaced by tryptophan. The
      carbohydrate-induced block of the channel function could be used also for the
      study of current noise through the different mutant LamB-channels. The analysis
      of the power density spectra of some of the mutants allowed the evaluation of the
      on-rate and off-rate constants (k1 and k(-1)) of carbohydrate binding to the
      binding site inside the channels. The results suggest that both on-rate and off
      rate constants were affected by the mutations. For most mutants, k1 decreased and
      k(-1) increased. The possible influence of the aromatic residues of the greasy
      slide on carbohydrate and ion transport through LamB is discussed.

PMID- 16095614
TI  - Functional dissection of the plant-specific SBP-domain: overlap of the DNA
      binding and nuclear localization domains.
AB  - SBP-domain proteins are plant-specific putative transcription factors. They all
      contain the highly conserved 76 amino acid residue SBP-domain, shown to bind
      specifically to related motifs in the Antirrhinum majus SQUA promoter and the
      orthologous Arabidopsis thaliana AP1 promoter. The structural basis for this
      sequence-specific binding of DNA are two Zn-finger like structures formed by the
      coordination of two zinc ions by conserved cysteine and histidine residues. Amino
      acid exchanges of the cysteine residues involved revealed that each of the Zn(2+)
      coordinating structures is essential for DNA binding. By random target-site
      selection studies, it is shown that the palindromic GTAC core motif is essential
      for efficient DNA binding with additional nucleotides preferred by different SBP
      domain proteins. Despite their different functions and origin from plants at
      different evolutionary distances, the mode of DNA binding is conserved from the
      single-cell algae Chlamydomonas reinhardtii to the moss Physcomitrella patens and
      higher plants. At the C-terminal end of the SBP-domain, a putative bipartite
      nuclear localization signal is located, which overlaps with the DNA-binding
      domain, in particular with the second Zn(2+)-binding structure. By
      immunolocalization of SPL3 and transient expression of SBP-green fluorescent
      protein fusion proteins in plant cells, it is shown that this nuclear
      localization signal is functional. Exchange of a highly conserved serine next to
      the nuclear localization signal by aspartate, which may mimic phosphorylation,
      resulted in a decreased nuclear import (SPL8), while DNA binding in vitro was
      abolished completely. In contrast, exchange by alanine increased nuclear import
      and left DNA binding intact. This suggests that the function of SBP-domain
      proteins is also regulated by post-translational modification on the levels of
      nuclear import and DNA binding.

PMID- 16095615
TI  - Multiple assembly pathways underlie amyloid-beta fibril polymorphisms.
AB  - The amyloid beta-protein transiently forms low and high molecular mass oligomers
      and protofibrils in vitro, and after longer incubation times assembles into
      polymorphic mature fibrils. The precursor-to-product relationship of these
      species remains to be understood. Protofibrils are up to approximately 600 nm in
      length and have mass-per-lengths of 19(+/-2) kDa/nm measured by scanning
      transmission electron microscopy. Two predominant mature fibril types, several
      microns in length and with mass-per-lengths of 18(+/-3) and 27(+/-3) kDa/nm, are
      identified after longer incubation times. The difference of approximately 9
      kDa/nm between the two fibril types indicates a bona fide elementary
      protofilament subunit of this mass-per-length. Fibrils in the 18(+/-3) kDa/nm
      group often exhibited distinct coiling with axial cross-over spacings of
      approximately 25 nm. Although strikingly different in morphology, the mass-per
      length (MPL) of these coiled fibrils is equivalent to that measured for
      protofibrils. They could therefore arise from a conformational change in the
      protofibril concurrent with coiling and rapid elongation. Alternatively, we
      cannot rule out an assembly pathway not directly related to protofibrils. In
      contrast, the 27(+/-3) kDa/nm fibrils correspond to a MPL of approximately 1.5 x
      the protofibril and thus can neither arise from a simple conformational
      transition nor from lateral association of 19 kDa/nm protofibril precursors.
      Twisted ribbons with axial periodicities ranging from approximately 80 nm to 130
      nm were prominent in the 27(+/-3) kDa/nm group as well as more tightly coiled
      fibrils. Individual fibril ribbons had elongation rates of 20(+/-12) nm/min when
      imaged by time-lapse atomic force microscopy. Protofibrils exhibited growth rates
      approximately 15 x slower at 1.3(+/-0.5) nm/min. The data support a model where
      concurrent multiple assembly pathways give rise to the various polymorphic fibril
      types.

PMID- 16095616
TI  - mu-1,2-peroxo diferric complex formation in horse spleen ferritin. A mixed H/L
      subunit heteropolymer.
AB  - Previous kinetics studies with homopolymer ferritins (bullfrog M-chain, human H
      chain and Escherichia coli bacterial ferritins) have established that a mu-1,2
      peroxo diferric intermediate is formed during Fe(II) oxidation by O2 at the
      ferroxidase site of the protein. The present study was undertaken to determine
      whether such an intermediate is formed also during iron oxidation in horse spleen
      ferritin (HoSF), a naturally occurring heteropolymer ferritin of H and L-subunits
      (approximately 3.3 H-chains/HoSF), and to assess its role in the formation of the
      mineral core. Multi-wavelength stopped-flow spectrophotometry of the oxidative
      deposition of iron in HoSF demonstrated that a transient peroxo complex
      (lambda(max) approximately 650 nm) is produced in this protein as for other
      ferritins. The peroxo complex in HoSF is formed about fourfold slower than in
      human H-chain (HuHF) and decays more slowly (approximately threefold) as well, at
      an iron level of two Fe(II)/H-chain. However, as found for HuHF, a second
      intermediate is formed in HoSF as a decay product of the peroxo complex. Only one
      third of the expected peroxo complex forms at the ferroxidase centers of HoSF
      when two Fe(II)/H-subunits are added to the protein, dropping to only
      approximately 14% when 20 Fe(II)/H-chain are added, indicating a declining role
      of the peroxo complex in iron deposition. In contrast to HuHF, HoSF does not
      enzymatically regenerate the observable peroxo complex. The kinetics of
      mineralization in HoSF are modeled satisfactorily by a mechanism in which the
      ferroxidase site rapidly produces an incipient core from a single turnover of
      iron, upon which subsequent Fe(II) is oxidized autocatalytically to build the
      Fe(O)OH(s) mineral core. This model supports a role for the L-chain in iron
      mineralization and helps to explain the widespread occurrence of heteropolymer
      ferritins in tissues of vertebrates.

PMID- 16095617
TI  - Characterization and functional analysis of CReMM, a novel chromodomain helicase
      DNA-binding protein.
AB  - The present study describes a newly identified protein named CReMM (chromatin
      related mesenchymal modulator). The protein was studied by bioinformatic means
      and classified as a member of the third subfamily of chromodomain helicase DNA
      binding proteins (CHD). In silico translation defined CReMM as a multiple domains
      protein including two chromodomains, SNF2/ATPase, helicase C domain and an A/T
      DNA-binding domain (DBD). Predicted extensive post-translation phosphorylation on
      serine and tyrosine residues was demonstrated by Western blot in the presence and
      in the absence of phosphatase inhibitors using specific antibodies.
      Immunoprecipitated CReMM disclosed a DNA-dependent ATPase activity quantified by
      colorimetric assay. Electrophoresis mobility-shift assay (EMSA) validated that
      CReMM binds to A/T-rich DNA. CReMM is expressed in mesenchymal progenitors, as
      shown in vitro and in vivo. CReMM protein structural motifs and proven
      biochemical activities highlight its role in chromatin remodeling. Further
      delineation of the function of this protein will provide information about its
      dynamics in transcriptional regulation of mesenchymal cells.

PMID- 16095618
TI  - Solution structure of the RIM1alpha PDZ domain in complex with an ELKS1b C
      terminal peptide.
AB  - PDZ domains are widespread protein modules that commonly recognize C-terminal
      sequences of target proteins and help to organize macromolecular signaling
      complexes. These sequences usually bind in an extended conformation to relatively
      shallow grooves formed between a beta-strand and an alpha-helix in the
      corresponding PDZ domains. Because of this binding mode, many PDZ domains
      recognize primarily the C-terminal and the antepenultimate side-chains of the
      target protein, which commonly conform to motifs that have been categorized into
      different classes. However, an increasing number of PDZ domains have been found
      to exhibit unusual specificities. These include the PDZ domain of RIMs, which are
      large multidomain proteins that regulate neurotransmitter release and help to
      organize presynaptic active zones. The RIM PDZ domain binds to the C-terminal
      sequence of ELKS with a unique specificity that involves each of the four ELKS C
      terminal residues. To elucidate the structural basis for this specificity, we
      have determined the 3D structure in solution of an RIM/ELKS C-terminal peptide
      complex using NMR spectroscopy. The structure shows that the RIM PDZ domain
      contains an unusually deep and narrow peptide-binding groove with an exquisite
      shape complementarity to the four ELKS C-terminal residues in their bound
      conformation. This groove is formed, in part, by a set of side-chains that is
      conserved selectively in RIM PDZ domains and that hence determines, at least in
      part, their unique specificity.

PMID- 16095619
TI  - X-ray structures of NADPH-dependent carbonyl reductase from Sporobolomyces
      salmonicolor provide insights into stereoselective reductions of carbonyl
      compounds.
AB  - The X-ray structures of red yeast Sporobolomyces salmonicolor carbonyl reductase
      (SSCR) and its complex with a coenzyme, NADPH, have been determined at a
      resolution of 1.8A and 1.6A, respectively. SSCR was crystallized in an
      orthorhombic system with the space group P2(1)2(1)2(1) and cell dimensions of
      a=54.86 A, b=83.49 A, and c=148.72 A. On its cocrystallization with NADPH,
      isomorphous crystals of the SSCR/NADPH complex were obtained. The structure of
      SSCR was solved by a single wavelength anomalous diffraction measurement using a
      selenomethionine-substituted enzyme, and that of the SSCR/NADPH complex was
      solved by a molecular replacement method using the solved structure of SSCR. The
      structures of SSCR and the SSCR/NADPH complex were refined to an R-factor of
      0.193 (R(free)=0.233) and 0.211 (R(free)=0.238), respectively. SSCR has two
      domains, an NADPH-binding domain and a substrate-binding domain, and belongs to
      the short-chain dehydrogenases/reductases family. The structure of the NADPH
      binding domain and the interaction between the enzyme and NADPH are very similar
      to those found in other structure-solved enzymes belonging to the short-chain
      dehydrogenases/reductases family, while the structure of the substrate-binding
      domain is unique. SSCR has stereoselectivity in its catalytic reaction, giving
      rise to excessive production of (S)-alcohols from ethyl 4-chloro-3-oxobutanoate.
      The X-ray structure of the SSCR/NADPH complex and preliminary modeling show that
      the formation of the hydrophobic channel induced by the binding of NADPH is
      closely related to the stereoselective reduction by SSCR.

PMID- 16095620
TI  - The crystal structure of Pyrococcus furiosus UMP kinase provides insight into
      catalysis and regulation in microbial pyrimidine nucleotide biosynthesis.
AB  - UMP kinase (UMPK), the enzyme responsible for microbial UMP phosphorylation,
      plays a key role in pyrimidine nucleotide biosynthesis, regulating this process
      via feed-back control and via gene repression of carbamoyl phosphate synthetase
      (the first enzyme of the pyrimidine biosynthesis pathway). We present crystal
      structures of Pyrococcus furiosus UMPK, free or complexed with AMPPNP or AMPPNP
      and UMP, at 2.4 A, 3 A and 2.55 A resolution, respectively, providing a true
      snapshot of the catalytically competent bisubstrate complex. The structure proves
      that UMPK does not resemble other nucleoside monophosphate kinases, including the
      UMP/CMP kinase found in animals, and thus UMPK may be a potential antimicrobial
      target. This enzyme has a homohexameric architecture centred around a hollow
      nucleus, and is organized as a trimer of dimers. The UMPK polypeptide exhibits
      the amino acid kinase family (AAKF) fold that has been reported in carbamate
      kinase and acetylglutamate kinase. Comparison with acetylglutamate kinase reveals
      that the substrates bind within each subunit at equivalent, adequately adapted
      sites. The UMPK structure contains two bound Mg ions, of which one helps
      stabilize the transition state, thus having the same catalytic role as one lysine
      residue found in acetylglutamate kinase, which is missing from P.furiosus UMPK.
      Relative to carbamate kinase and acetylglutamate kinase, UMPK presents a
      radically different dimer architecture, lacking the characteristic 16-stranded
      beta-sheet backbone that was considered a signature of AAKF enzymes. Its
      hexameric architecture, also a novel trait, results from equatorial contacts
      between the A and B subunits of adjacent dimers combined with polar contacts
      between A or B subunits, and may be required for the UMPK regulatory functions,
      such as gene regulation, proposed here to be mediated by hexamer-hexamer
      interactions with the DNA-binding protein PepA.

PMID- 16095621
TI  - Properties of motility in Bacillus subtilis powered by the H+-coupled MotAB
      flagellar stator, Na+-coupled MotPS or hybrid stators MotAS or MotPB.
AB  - Bacillus subtilis has a single set of flagellar rotor proteins that interact with
      two distinct stator-force generators, the H+-coupled MotAB complex and the Na+
      coupled MotPS complex, that energize rotation. Here, motility on soft agar plates
      and in liquid was assayed in wild-type B.subtilis and strains expressing only one
      stator, either MotAB, MotPS or hybrid MotAS or MotPB. The strains expressing
      MotAB or MotAS had an average of 11 flagella/cell while those expressing MotPS or
      MotPB had an average of seven flagella/cell, and a Mot-less double mutant had
      three to four flagella/cell. MotAB had a more dominant role in motility than
      MotPS under most conditions, but MotPS supported comparable motility to MotAB on
      malate-containing soft agar plating media at elevated pH and Na+. MotAB supported
      much faster swimming speeds in liquid than MotPS, MotAS or MotPB under all
      conditions, but a contribution of MotPS to wild-type swimming was discernible
      from differences in swimming speeds of wild-type and MotAB at elevated viscosity,
      pH and Na+. Swimming supported by MotPS and MotAS was stimulated by Na+ and
      elevated pH whereas the converse was true of MotAB and MotPB. This suggests that
      MotAS is Na+-coupled and MotPB is H+-coupled and that MotB and MotS are major
      determinants of ion-coupling. However, the swimming speed supported by MotPB, as
      well as MotPS and MotAS, was inhibited severely at Na+ concentrations above 300
      mM whereas MotAB-dependent swimming was not. The presence of either the MotP or
      MotS component in the stator also conferred sensitivity to inhibition by an
      amiloride analogue. These observations suggest that MotP contributes to Na+
      coupling and inhibition by Na+ channel inhibitors. Similarly, a role for MotA in
      H+-dependent stator properties is indicated by the larger effects of pH on the
      Na+-response of MotAS versus MotPS. Finally, optimal function at elevated
      viscosity was found only in MotPS and MotPB and is therefore conferred by MotP.

PMID- 16095622
TI  - Crystal structure of 6-hydroxy-D-nicotine oxidase from Arthrobacter
      nicotinovorans.
AB  - The crystal structure of 6-hydroxy-d-nicotine oxidase (EC 1.5.3.6) was solved by
      X-ray diffraction analysis in three crystal forms at resolutions up to 1.9 A. The
      enzyme is monomeric in solution and also in the mother liquor but formed
      disulfide-dimers in all crystals. It belongs to the p-cresol methylhydroxylase
      vanillyl-alcohol oxidase family and contains an FAD covalently bound to the
      polypeptide. The covalent bond of this enzyme was the first for which a purely
      autocatalytic formation had been shown. In contrast to previous reports, the bond
      does not involve N(epsilon2) (N3) of His72 but the N(delta1) (N1) atom. The
      geometry of this reaction is proposed and the autoflavinylation is discussed in
      the light of homologous structures. The enzyme is specific for 6-hydroxy-D
      nicotine and is inhibited by the L-enantiomer. This observation was verified by
      modeling enzyme-substrate and enzyme-inhibitor complexes, which also showed the
      geometry of the catalyzed reaction. The binding models indicated that the
      deprotonation of the substrate rather than the hydride transfer is the
      specificity-determining step. The functionally closely related 6-hydroxy-L
      nicotine oxidase processing the L-enantiomer is sequence-related to the greater
      glutathione reductase family with quite a different chainfold. A model of this
      "sister enzyme" derived from known homologous structures suggests that the
      reported L-substrate specificity and D-enantiomer inhibition are also determined
      by the location of the deprotonating base.

PMID- 16095623
TI  - Cooperative reorganization of a 420 subunit virus capsid.
AB  - The complex protein capsids of many viruses exhibit dramatic reorganizations at
      critical stages in their life-cycle. Here, time-resolved solution X-ray
      scattering was used to study a dynamic, large-scale conformational maturation of
      the 420 subunit, 13 MDa, icosahedrally symmetric HK97 bacteriophage capsid.
      Isoscattering points in the time-resolved scattering patterns and singular value
      decomposition revealed that the expansion occurs as a cooperative, two-state
      reaction. The analysis demonstrates that the population shift from Prohead-II to
      Expansion Intermediate I, EI-I (60 A larger than Prohead-II) occurs in minutes,
      but does not reveal the time required for individual transitions that occur
      stochastically. Any intermediate forms that may be traversed during this
      conversion are unstable and do not constitute an appreciable population of the
      ensemble of particles. In an energetic landscape view, particles must undergo an
      energy barrier-crossing event in order to successfully convert from Prohead-II to
      EI-I. This implies that the particles "hop" over the energy barrier
      stochastically as they individually attain an expansion-active state.
      Interestingly, systematic deviations from single-exponential kinetics were
      observed for the population shift. This may indicate that in undergoing the
      irreversible conversion from Prohead-II to EI-I, particles are subject to a
      complex energy landscape that links the initial and final particle forms.

PMID- 16095624
TI  - Modelling the evolution of genetic regulatory networks.
AB  - An evolutionary model of genetic regulatory networks is developed, based on a
      model of network encoding and dynamics called the Artificial Genome (AG). This
      model derives a number of specific genes and their interactions from a string of
      (initially random) bases in an idealized manner analogous to that employed by
      natural DNA. The gene expression dynamics are determined by updating the gene
      network as if it were a simple Boolean network. The generic behaviour of the AG
      model is investigated in detail. In particular, we explore the characteristic
      network topologies generated by the model, their dynamical behaviours, and the
      typical variance of network connectivities and network structures. These
      properties are demonstrated to agree with a probabilistic analysis of the model,
      and the typical network structures generated by the model are shown to lie
      between those of random networks and scale-free networks in terms of their degree
      distribution. Evolutionary processes are simulated using a genetic algorithm,
      with selection acting on a range of properties from gene number and degree of
      connectivity through periodic behaviour to specific patterns of gene expression.
      The evolvability of increasingly complex patterns of gene expression is examined
      in detail. When a degree of redundancy is introduced, the average number of
      generations required to evolve given targets is reduced, but limits on evolution
      of complex gene expression patterns remain. In addition, cyclic gene expression
      patterns with periods that are multiples of shorter expression patterns are shown
      to be inherently easier to evolve than others. Constraints imposed by the
      template-matching nature of the AG model generate similar biases towards such
      expression patterns in networks in initial populations, in addition to the
      somewhat scale-free nature of these networks. The significance of these results
      on current understanding of biological evolution is discussed.

PMID- 16095625
TI  - Fast-tracking morphogen diffusion.
AB  - The readout of morphogen concentrations has been proposed to be an essential
      mechanism allowing embryos to specify cell identities [Wolpert Trends Genet 12
      (1996) 359], but theoretical and experimental results have led to conflicting
      ideas as to how useful concentration gradients can be established. In particular,
      it has been pointed out that some models of passive extracellular diffusion
      exhibit traveling waves of receptor saturation, inadequate for the establishment
      of positional information. Two alternative (but not mutually exclusive) models
      are proposed here, which are based on recent experimental results highlighting
      the roles of extracellular glycoproteins and morphogen oligomerization. In the
      first model, inspired from the interactions of Dally and Dally-like with Wingless
      and Decapentaplegic in the third-instar Drosophila wing disc, two morphogen
      populations are considered: one in a cell-membrane phase, and another one in an
      extracellular matrix phase, which does not interact with receptors; in the second
      model, inspired from biochemical studies of Sonic Hedgehog, morphogen oligomers
      are considered to diffuse freely without interacting with receptors. The
      existence of a dynamic sub-population of freely diffusing morphogen allows the
      system to establish a gradient of bound receptor that is suitable for the
      specification of positional information. Recent experimental results are
      discussed within the framework of these models, as well as further possible
      experiments. The role of Notum in the setup of the Wg gradient is also shown to
      be likely not to involve a gradient in Notum distribution, even though Notum is
      only expressed close to the source of Wg synthesis.

PMID- 16095626
TI  - Development of a system of indicators for sustainable port management.
AB  - The 1998 project ECOPORT, "Towards A Sustainable Transport Network", developed by
      the Valencia Port Authority (VPA), established the bases for implementing an
      Environmental Management System (EMS) in industrial harbours. The use of data and
      information shall always be required to develop an efficient EMS. The objective
      of the present research (INDAPORT) study is to propose a system of sustainable
      environmental management indicators to be used by any port authorities. All
      activities performed within a port area are analysed for any potential
      environmental impacts and risks. An environmental analysis of port activities has
      been carried out with the objective of designing the indicators system. Twenty
      one corresponding activities have been identified for large industrial ports.
      Subsequently, the same methodology developed to date will be later applied to
      other Spanish and European ports. The study has been developed by using an
      original system and a methodology, which simultaneously use stage diagrams and
      systemic models (material and energy flow charts). Multi-criteria analysis
      techniques were used to evaluate potential impacts (identification of factors and
      evaluation of impacts).

PMID- 16095627
TI  - Vaccination against multiple HPV types.
AB  - Vaccines against the most common human papillomavirus (HPV) types are currently
      under development. Epidemiologic data suggest that the transmission dynamics of
      different HPV types are not independent. Some studies indicate that interactions
      among HPV types are synergistic, where infection with one type facilitates
      concurrent or subsequent infection with another HPV type. Other studies point to
      antagonistic interference among HPV types. Here we develop a mathematical model
      to explore how these interactions may either enhance or diminish the
      effectiveness of vaccination programs designed to reduce the prevalence of the
      HPV types associated with cervical cancer. We analyze the local stability of the
      infection-free and boundary equilibria and characterize the conditions leading to
      a coexistence equilibrium. We also illustrate the results with numerical
      simulations using realistic model parameters. We show that if interactions among
      HPV types are synergistic, mass vaccination may reduce the prevalence of types
      that are not even included in the vaccine.

PMID- 16095628
TI  - Role of cyclic ADP-ribose in Ca2+-induced Ca2+ release and vasoconstriction in
      small renal arteries.
AB  - Cyclic-ADP-ribose (cADPR) has been reported to serve as a second messenger to
      mobilize intracellular Ca2+ independent of IP3 in a variety of mammalian cells.
      This cADPR-mediated Ca2+ signaling pathway importantly participates in the
      regulation of various cell functions. The present study determined the role of
      endogenous cADPR in mediating ryanodine-sensitive Ca2+-induced Ca2+ release
      (CICR) in vascular myocytes from small renal arteries and vasomotor response of
      these arteries. In freshly-isolated renal arterial myocytes, addition of CaCl2
      (0.01, 0.1, and 1 mM) into the Ca2+-free bath solution produced a rapid Ca2+
      release response from the sarcoplasmic reticulum (SR), with a maximal increase of
      237+/-25 nM at 1 mM CaCl2. This CaCl2 response was significantly blocked by a
      cell-membrane permeant cADPR antagonist, 8-bromo-cADP-ribose (8-br-cADPR) (30
      microM) or ryanodine (50 microM). Caffeine, a classical CICR or ryanodine
      receptor activator was found to stimulate the SR Ca2+ release (Delta[Ca2+]i:
      253+/-35 nM), which was also attenuated by 8-br-cADPR or ryanodine. Using
      isolated and pressurized small renal arteries bathed with Ca2+-free solution,
      both CaCl2 and caffeine-induced vasoconstrictions were significantly attenuated
      by either 8-br-cADPR or ryanodine. Biochemical analyses demonstrated that CaCl2
      and caffeine did not increase cADPR production in these renal arterial myocytes,
      but confocal microscopy showed that a dissociation of the accessory protein,
      FK506 binding protein 12.6 (FKBP12.6) from ryanodine receptors was induced by
      CaCl2. We conclude that cADPR importantly contributes to CICR and vasomotor
      responses of small renal arteries through enhanced dissociation of ryanodine
      receptors from their accessory protein.

PMID- 16095629
TI  - Vessel painting of the microcirculation using fluorescent lipophilic tracers.
AB  - Flexible approaches to defining microvessel morphometry are useful in the study
      of both acute and chronic structural changes of the microcirculation. In this
      report, we examined the utility of the intravascular infusion of lipophilic
      carbocyanine tracers in the structural assessment of the retina, skin, lung, and
      colon microcirculation. The microvessel labeling technique, here termed
      fluorescent vessel painting, involved the intravascular injection of sulfonated
      lipophilic carbocyanine tracers. The utility of vessel painting in morphometry
      was assessed using morphometric comparisons with corrosion casting and 2
      dimensional and 3-dimensional scanning electron microscopy. The comparisons
      demonstrated that fluorescent vessel painting modestly overestimated the
      interbranch angles, interbranch distances, and vessel diameters of the 2D mucosal
      plexus of the colon. These differences were narrowed with the application of
      confocal microscopy. The advantages of fluorescence vessel painting included (1)
      the filling of all tissues including the relatively high resistance microvessels
      of the mouse skin, (2) the ability to use tissue counterstains such as DAPI, and
      (3) the prolonged stability of the lipophilic tracer after aldehyde fixation.
      These studies suggest the utility of fluorescent vessel painting as a
      complementary technique to corrosion casting in the morphometric study of the
      microcirculation.

PMID- 16095630
TI  - The potential mechanisms involved in the anti-carcinogenic action of probiotics.
AB  - Probiotic bacteria are live microbial food ingredients that provide a health
      benefit to the consumer. In the past it was suggested that they served to benefit
      the host primarily through the prevention of intestinal infections. More recent
      studies have implicated probiotic bacteria in a number of other beneficial
      effects within the host including: *The suppression of allergies. *Control of
      blood cholesterol levels. *Modulation of immune function. *And the prevention of
      cancers of the colon. The reputed anti-carcinogenic effect of probiotics arises
      from in vivo studies in both animals and to a limited extent in man; this
      evidence is supported by in vitro studies with carcinoma cell lines and anti
      mutagenicity assays. However, the mechanisms involved in any effect have thus far
      been difficult to elucidate; studies offer evidence for a variety of mechanisms;
      we have reviewed these and come to the opinion that, the anti-carcinogenic effect
      may not be attributable to a single mechanism but rather to a combination of
      events not yet fully elucidated or understood.

PMID- 16095631
TI  - Protective effects of green tea polyphenol extracts against ethanol-induced
      gastric mucosal damages in rats: stress-responsive transcription factors and MAP
      kinases as potential targets.
AB  - There are multiple lines of compelling evidence from epidemiologic and laboratory
      studies supporting that frequent consumption of green tea is inversely associated
      with the risk of chronic human diseases including cancer. The chemopreventive and
      chemoprotective effects of green tea have been largely attributed to
      antioxidative and anti-inflammatory activities of its polyphenolic constituents,
      such as epigallocatechin gallate. The present study was designed to evaluate the
      efficacy of green tea polyphenols in protecting against alcohol-induced gastric
      damage and to elucidate the underlying mechanisms. Intragastric administration of
      ethanol to male Sprague-Dawley rats caused significant gastric mucosal damage,
      which was accompanied by elevated expression of cyclooxygenase-2 (COX-2) and
      inducible nitric oxide synthase (iNOS) as well as transient activation of redox
      sensitive transcription factors, such as NF-kappaB and AP-1, and mitogen
      activated protein kinases (MAPKs). Oral administration of the green tea
      polyphenolic extract (GTE) significantly ameliorated mucosal damages induced by
      ethanol and also attenuated the ethanol-induced expression of COX-2 and iNOS.
      Inactivation of MAPKs, especially p38 and ERKl/2, by GTE might be responsible for
      inhibition of ethanol-induced expression of COX-2 and iNOS.

PMID- 16095632
TI  - Seasonal variations of DNA damage in human lymphocytes: correlation with
      different environmental variables.
AB  - Several types of DNA damage, including DNA breaks and DNA base oxidation, display
      a seasonal trend. In the present work, a sample of 79 healthy subjects living in
      the city of Florence, Italy, was used to analyse this effect. Three possible
      causative agents were taken into consideration: solar radiation, air temperature
      and air ozone level. DNA damage was measured in isolated human lymphocytes at
      different times during the year and the observed damage was correlated with the
      levels of these three agents in the days preceding blood sampling. Three time
      windows were chosen: 3, 7 and 30 days before blood sampling. DNA strand breaks
      and the oxidized purinic bases cleaved by the formamidopyrimidine glycosylase
      (FPG sites) were measured by means of the comet assay. The results of
      multivariate regression analysis showed a positive correlation between lymphocyte
      DNA damage and air temperature, and a less strong correlation with global solar
      radiation and air ozone levels.

PMID- 16095633
TI  - Analysis of the spontaneous mutator phenotype associated with 20S proteasome
      deficiency in S. cerevisiae.
AB  - Besides its role as a major recycler of unfolded or otherwise damaged
      intracellular proteins, the 26S proteasome functions as a regulator of many vital
      cellular processes and is postulated as a target for antitumor drugs. It has
      previously been shown that dysfunction of the catalytic core of the 26S
      proteasome, the 20S proteasome, causes a moderate increase in the frequency of
      spontaneous mutations in yeast [A. Podlaska, J. McIntyre, A. Skoneczna, E.
      Sledziewska-Gojska, The link between proteasome activity and postreplication DNA
      repair in Saccharomyces cerevisiae. Mol. Microbiol. 49 (2003) 1321-1332]. Here we
      show the results of genetic analysis, which indicate that the mutator phenotype
      caused by the deletion of UMP1, encoding maturase of 20S proteasome, involves
      members of the RAD6 epistasis group. The great majority of mutations occurring
      spontaneously in yeast cells deficient in 20S proteasome function are connected
      with the unique Rad6/Rad18-dependent error-prone translesion DNA synthesis (TLS)
      requiring the activities of both TLS polymerases: Pol eta and Pol zeta. Our
      results suggest the involvement of proteasomal activity in the limitation of this
      unique error-prone TLS mechanism in wild-type cells. On the other hand, we found
      that the mutator phenotypes caused by deficiency in Rad18 and Rad6, are largely
      alleviated by defects in proteasome activities. Since the mutator phenotypes
      produced by deletion of RAD6 and RAD18 require Pol zeta and Siz1/Ubc9-dependent
      sumoylation of PCNA, our results suggest that proteasomal dysfunction limits
      sumoylation-dependent error-prone activity of Pol zeta. Taken together, our
      findings strongly support the idea that proteolytic activity is involved in
      modulating the balance between TLS mechanisms functioning during DNA replication
      in S. cerevisiae.

PMID- 16095634
TI  - Mechanistic approaches to chemoprevention of mutation and cancer.
AB  - This is the eighth special issue of 'Mutation Research' to focus on
      antimutagenesis and anticarcinogenesis. It covers a wide range of mechanisms from
      prevention of cancer initiation by antimutagens through to inhibition of tumour
      angiogenesis and selective estrogen receptor modulators. New screening methods
      and new biomarkers are also elucidated. There is increasing reason to believe
      that the long-term use of a combination of anticarcinogens, over an extended time
      span, may provide a realistic prospect of reducing the current burden of human
      cancers.

PMID- 16095635
TI  - Effect of a selective GABA(B) receptor agonist baclofen on the mu-opioid receptor
      agonist-induced antinociceptive, emetic and rewarding effects.
AB  - The management of excessive adverse effects of opioids is a major clinical
      problem. The present study was undertaken to investigate the effect of a
      selective gamma-aminobutyric acid (GABA)(B) receptor agonist baclofen on the mu
      opioid receptor agonist-induced antinociceptive, emetic and rewarding effects.
      Either morphine or fentanyl produced a dose-dependent antinociceptive effect in
      both ferrets using Randall-Selitto test and mice using tail-flick test. Under
      these conditions, pretreatment of baclofen produced an additive antinociception
      induced by morphine or fentanyl. Furthermore, the augmentation of antinociception
      induced by systemic administration of baclofen with morphine or fentanyl was
      completely abolished by either i.c.v. or i.t. pretreatment with the selective
      GABA(B) receptor antagonist CGP 35348 in mice. We next investigated the emetic
      response induced by mu-opioid receptor agonist in ferrets. Morphine at lower
      doses than that used for antinociceptive assay produced both retching and
      vomiting, whereas fentanyl failed to produce the retching and vomiting in
      ferrets. Here we reported for the first time that baclofen significantly
      suppressed the retching and vomiting induced by morphine, indicating the
      involvement of GABA(B) receptor in emetic control pathway. Furthermore, baclofen
      also inhibited place preference elicited morphine or fentanyl in rats. Taken
      together, these results suggest that co-administration of baclofen with mu-opioid
      receptor agonist produced a potentiation of antinociceptive effect, whereas an
      untoward effect was completely blocked.

PMID- 16095636
TI  - Design, synthesis, and evaluation of the antipsychotic potential of orally
      bioavailable neurotensin (8-13) analogues containing non-natural arginine and
      lysine residues.
AB  - Neurotensin (NT) and its active fragment NT(8-13) elicit behavioral responses
      typical of clinically used antipsychotic drugs when administered directly to the
      brain. However, limited peptide stability and oral bioavailability have prevented
      these compounds from being developed as relevant pharmaceuticals. Recently, our
      laboratory designed and studied a first-generation NT(8-13) derivative, KK13,
      that elicited key pharmacokinetic and behavioral responses typical of clinically
      used antipsychotic drugs when administered to rats parenterally. This compound
      was the basis for the rational design of a series of second-generation NT(8-13)
      analogues (KH1-KH30) studied in this paper. Initial screening of these analogues
      for CNS activity by monitoring hypothermia induction after peripheral
      administration defined several compounds (KH11, KH24, KH26, and KH28-KH30) that
      warranted further investigation. Each compound maintained binding affinity for
      NTR(1), however, only KH24, KH26, and KH28 (as well as KK13) elicited significant
      hypothermic responses after oral administration. Of these, KH28 demonstrated an
      oral activity 3-fold greater than any other analogue; hence it was further
      characterized in a series of rat behavioral assays. KH28 attenuated d-amphetamine
      induced hyperlocomotion, a hallmark of current clinically effective antipsychotic
      drugs, after both IP and oral administration. In addition, tolerance to the
      compound did not develop after repeated daily dosing, as measured by hypothermic
      induction as well as attenuation of d-amphetamine induced hyperlocomotion.
      Finally, KH28 did not produce catalepsy, a deleterious side-effect elicited by
      classical antipsychotic drugs. KH28 is considered to be an ideal compound for
      further development as a potential novel antipsychotic.

PMID- 16095637
TI  - Electrophysiological activity underlying inhibitory control processes in normal
      adults.
AB  - In a recent ERP study of inhibitory control using the Stop-Signal Task [Pliszka,
      S., Liotti, M., Woldorff, M. (2000). Inhibitory control in children with
      attention-deficit/hyperactivity disorder: Event-related potentials identify the
      processing component and timing of an impaired right-frontal response-inhibition
      mechanism. Biological Psychiatry, 48, 238-246], we showed that in normal children
      (age 10-12 years) the Stop Signals elicited a robust, right-frontal-maximal N200
      (latency approximately 200 ms) that was strongly reduced in children with ADHD.
      To further investigate the mechanisms of response inhibition, this paradigm was
      applied to 11 healthy young adults. To better distinguish response-inhibition
      related activity from early attentional effects, a "Stop-Signal-Irrelevant"
      condition was added, in which subjects performed the task while ignoring the Stop
      Signals. In the Stop-Signal-Relevant condition, the right frontal N200 to the
      Stop Signals was larger for Successful inhibition (SI) than for Failed inhibition
      (FI) trials. The timing and distribution of this effect was strikingly similar to
      that of the right-frontal ADHD deficit reported in Pliszka et al. (2000),
      supporting this activity being related to successful normal inhibitory control
      processes. In contrast, a posterior N200 was larger for Stop-Relevant than for
      Stop-Irrelevant trials, likely reflecting enhanced early sensory attention to the
      Stop Signals when relevant. Two longer-latency failure-specific ERP effects were
      also observed: a greater frontopolar negative wave (370-450 ms) to Failed than
      Successful inhibitions, and a greater parietal positive slow wave (450-650 ms)
      for Failed inhibitions than ignore-stop trials, likely reflecting differential
      recruitment of error detection and correction mechanisms following Failed
      attempts to inhibit a response.

PMID- 16095638
TI  - Effects of social isolation on aging-induced orofacial movements in rats.
AB  - World population is becoming older, and aging is a common risk factor for a
      number of pathologies. In this respect, it is important to study possible factors
      that could modify alterations implicated in the process of aging. The aim of the
      present study is to verify the effects of social isolation on the expression of
      orofacial movements in adult and old rats. Adult and old rats were housed
      isolated for 5 days or kept in their home cages in groups of six. Before and
      after this period, orofacial movements and open-field general activity were
      evaluated. Aging-induced orofacial movements were abolished by isolation. On the
      other hand, isolated adult rats presented an increase in orofacial movements.
      General activity was decreased by aging but was not modified by isolation. Our
      results indicate that social isolation produces different effects in adult and
      old rats, and these effects are specific for orofacial movements and not related
      to a decrease in general motor activity.

PMID- 16095639
TI  - Ambient odors of orange and lavender reduce anxiety and improve mood in a dental
      office.
AB  - The goal of this study was to investigate the impact of the essential oils of
      orange and lavender on anxiety, mood, alertness and calmness in dental patients.
      Two hundred patients between the ages of 18 and 77 years (half women, half men)
      were assigned to one of four independent groups. While waiting for dental
      procedures patients were either stimulated with ambient odor of orange or ambient
      odor of lavender. These conditions were compared to a music condition and a
      control condition (no odor, no music). Anxiety, mood, alertness and calmness were
      assessed while patients waited for dental treatment. Statistical analyses
      revealed that compared to control condition both ambient odors of orange and
      lavender reduced anxiety and improved mood in patients waiting for dental
      treatment. These findings support the previous opinion that odors are capable of
      altering emotional states and may indicate that the use of odors is helpful in
      reducing anxiety in dental patients.

PMID- 16095640
TI  - Phenylpropanoid glucosides from leaves of Coussarea hydrangeifolia (Rubiaceae).
AB  - Phenylpropanoid glycosides, 1'-O-benzyl-alpha-L-rhamnopyranosyl-(1''-->6')-beta-D
      glucopyranoside (1) and alpha-L-xylopyranosyl-(4''-->2')-(3-O-beta-D
      glucopyranosyl)-1'-O-E-caffeoyl-beta-D-glucopyranoside (2), together with the
      known derivatives, 1,6-di-O-caffeoyl-beta-D-glucopyranoside (3), 1-O-(E)-caffeoyl
      beta-D-glucopyranoside (4) and 1-O-(E)-feruloyl-beta-D-glucopyranoside (5), were
      isolated from leaves of Coussarea hydrangeifolia. Their structures were
      determined by IR, HRESIMS, and 1D and 2D NMR experiments, and their antioxidant
      activities, evaluated by assaying the free radical scavenging capacity using the
      DPPH (1,1-diphenyl-2-picrylhydrazyl) radical as substrate. The antioxidant
      activities of 3 and 4 (IC50 values of 15.0 and 19.2 microM, respectively) were
      comparable to that of the standard positive control caffeic acid, whilst 2 and 5
      were only weakly active and 1 was inactive.

PMID- 16095641
TI  - Usefulness of PCR in the diagnosis of cutaneous leishmaniasis in Tunisia.
AB  - We assessed the efficiency of a PCR method in establishing the diagnosis of
      cutaneous leishmaniasis (CL) in Tunisian patients. Four hundred and thirty
      specimens collected passively from patients with cutaneous ulcers suggestive of
      leishmaniasis attending health centres for diagnosis were included in the study.
      Dermal scrapings were analysed both by parasitological (examination of Giemsa
      stained smears and in vitro cultivation) methods and by a genus-specific PCR
      detecting a fragment of the 18S rRNA gene. Microscopy revealed amastigotes in 245
      samples (57.0%) and in vitro cultivation gave positive results in 88 cases
      (20.5%), whereas PCR detected Leishmania in 301 samples (70%). The sensitivities
      inferred from our results were 99.3%, 80.8% and 29% for PCR, microscopic
      examination and in vitro cultivation, respectively. The different forms of CL in
      this country are caused by three species of Leishmania and are treated with the
      same protocol. Of 303 well-documented cases in our study, 99% were probably
      caused by Leishmania major and 1% by Leishmania infantum. The lack of species
      specific diagnosis is not known to affect treatment or prognosis in Tunisia.
      These data support the incorporation of PCR into diagnostic strategies for CL,
      particularly in Tunisia.

PMID- 16095642
TI  - Application of a user-friendly Brucella-specific IgM and IgG antibody assay for
      the rapid confirmation of Rose Bengal-positive patients in a hospital in Iran.
AB  - The Brucella IgM/IgG flow assay was used for the confirmation of brucellosis in
      patients from an area endemic for brucellosis and who had a Rose Bengal (RB)
      positive serum sample collected at the time of first presentation for diagnosis.
      The flow assay confirmed the result of the RB test in 46.6% of the positive
      admission sera, with the majority (62.5%) of the flow assay-positive samples
      staining moderately strong to very strong (> or =2+). In comparison, Wright and 2
      ME at the routinely used cut-off titre values of 1:320 for Wright and 1:160 for 2
      ME tested positive in 37.7% of the RB-positive samples. A relatively large number
      of RB-positive samples agglutinated at or around the cut-off value in the Wright
      and 2-ME tests and 66.7% of the RB-positive samples tested positive in these
      confirmatory tests when using one titre step lower threshold values. The
      relatively high number of samples with low antibody levels supports the argument
      for testing follow-up samples from patients with an RB-positive sample in order
      to confirm the diagnosis by showing seroconversion or a rise in antibody levels.

PMID- 16095643
TI  - Efficacy of chloroquine + sulfadoxine--pyrimethamine, mefloquine + artesunate and
      artemether + lumefantrine combination therapies to treat Plasmodium falciparum
      malaria in the Chittagong Hill Tracts, Bangladesh.
AB  - Bangladesh faces growing levels of Plasmodium falciparum resistance to
      chloroquine (CQ) and sulfadoxine-pyrimethamine (SP). Alternative antimalarial
      therapies, particularly combination regimens, need to be considered. Therefore,
      the efficacy of three antimalarial combination therapies was assessed in
      Chittagong Hill Tracts. A total of 364 P. falciparum patients were recruited and
      randomly assigned to either CQ + SP, mefloquine + artesunate (MQ + AS) or
      lumefantrine + artemether (Coartem). Results showed that CQ + SP therapy was less
      effective than the two artemisinin-based combination therapies. The day 42 PCR
      corrected efficacy rate was 62.4% for CQ + SP, 100% for MQ + AS and 97.1% for
      Coartem. Failures occurred at a shorter interval after CQ + SP treatment than
      after Coartem. The artemisinin-based therapies effectively prevented development
      of gametocytes, whereas CQ + SP did not. All three therapies were well tolerated,
      although reports of mild complaints during treatment appeared higher with MQ +
      AS. We conclude that CQ + SP is not a viable option for replacing CQ monotherapy
      as first-line P. falciparum treatment in this area of Bangladesh. A change to
      artemisinin-based combination therapy is recommended. Both Coartem and MQ + AS
      appear to be good options, effective in curing P. falciparum malaria and in
      preventing recrudescences following treatment.

PMID- 16095644
TI  - Homo-oligomerization facilitates the interferon-antagonist activity of the
      ebolavirus VP35 protein.
AB  - We have identified a putative coiled-coil motif within the amino-terminal half of
      the ebolavirus VP35 protein. Cross-linking studies demonstrated the ability of
      VP35 to form trimers, consistent with the presence of a functional coiled-coil
      motif. VP35 mutants lacking the coiled-coil motif or possessing a mutation
      designed to disrupt coiled-coil function were defective in oligomerization, as
      deduced by co-immunoprecipitation studies. VP35 inhibits signaling that activates
      interferon regulatory factor 3 (IRF-3) and inhibits (IFN)-alpha/beta production.
      Experiments comparing the ability of VP35 mutants to block IFN responses
      demonstrated that the VP35 amino-terminus, which retains the putative coiled-coil
      motif, was unable to inhibit IFN responses, whereas the VP35 carboxy-terminus
      weakly inhibited the activation of IFN responses. IFN-antagonist function was
      restored when a heterologous trimerization motif was fused to the carboxy
      terminal half of VP35, suggesting that an oligomerization function at the amino
      terminus facilitates an "IFN-antagonist" function exerted by the carboxy-terminal
      half of VP35.

PMID- 16095645
TI  - Bioluminescence imaging of vaccinia virus: effects of interferon on viral
      replication and spread.
AB  - Whole animal imaging allows viral replication and localization to be monitored in
      intact animals, which provides significant advantages for determining viral and
      host factors that determine pathogenesis. To investigate effects of interferons
      on spatial and temporal progression of vaccinia infection, we generated
      recombinant viruses that express firefly luciferase or a monomeric orange
      fluorescent protein. These viruses allow vaccinia infection to be monitored with
      bioluminescence or fluorescence imaging, respectively. The recombinant viruses
      were not attenuated in vitro or in vivo relative to a control WR virus. In cell
      culture, reporters could be detected readily by 4 h post-infection, showing that
      these viruses can be used as early markers of infection. The magnitude of firefly
      luciferase activity measured with bioluminescence imaging in vitro and in vivo
      correlated directly with increasing titers of vaccinia virus, validating imaging
      data as a marker of viral infection. Replication of vaccinia was significantly
      greater in mice lacking receptors for type I interferons (IFN I R-/-) compared
      with wild-type mice, although both genotypes of mice developed focal infections
      in lungs and brain after intranasal inoculation. IFN I R-/- mice had greater
      dissemination of virus to liver and spleen than wild-type animals even when
      mortality occurred at the same time point after infection. Protective effects of
      type I interferons were mediated primarily through parenchymal cells rather than
      hematopoietic cells as analyzed by bone marrow transplant experiments.
      Collectively, our data define a new function for type I interferon signaling in
      systemic dissemination of vaccinia and validate these reporter viruses for
      studies of pathogenesis.

PMID- 16095646
TI  - Evaluation of rotavirus dsRNA load in specimens and body fluids from
      experimentally infected juvenile macaques by real-time PCR.
AB  - We recently established a non-human primate model of rotavirus infection that is
      characterized by consistent and high levels of virus antigen shedding in stools.
      Here, we report that starting from post challenge day (PCD) 2, 6 x 10(3) to 1.5 x
      10(6) copies of rotavirus double-stranded RNA per nanogram of total RNA were
      detected by real-time PCR in MA104 cells that were 48 h pre-incubated with
      filtered stool suspensions of three experimentally infected juvenile macaques.
      The peak of virus load was detected at PCD 4-5, followed by decreased load at PCD
      6-11, and very low levels at PCD 12. Such a pattern corresponded to virus
      shedding in stools as reported recently based on enzyme-linked immunosorbent
      assay (ELISA) results. In addition, plasma and cerebrospinal fluids (CSF) from
      six infected animals were tested for the presence of rotavirus. Rotavirus
      extraintestinal escape was revealed in three out of six animals by a combination
      of real-time and nested PCR. However, very low quantities of detected viral RNA
      (approximately 20 copies/ng of total RNA) were not suggestive of viremia. Thus,
      the rhesus model of rotavirus infection can be exploited further in studies with
      vaccine candidates designed to prevent or abrogate rotavirus infection.

PMID- 16095647
TI  - The role of protein kinase activity expressed by the UL13 gene of herpes simplex
      virus 1: the activity is not essential for optimal expression of UL41 and ICP0.
AB  - Herpes simplex virus 1 (HSV-1) UL13 is a viral protein kinase that is packaged
      into virions and regulates optimal expression of ICP0 and a subset of late
      (gamma) proteins, including UL41 in infected cells. In the present study, we
      investigated the role(s) of the protein kinase activity of UL13 in viral
      replication using a recombinant virus expressing enzymatically inactive UL13
      after an amino acid substitution in the invariant lysine of UL13. The recombinant
      virus carrying this mutation formed smaller plaques yielded 10-fold less progeny
      than wild-type virus but could not be differentiated from wild-type virus with
      respect to accumulation of UL41 and ICP0 in infected cells. These results
      indicate that the protein kinase activity of UL13 plays a role in viral
      replication in cell culture, but the activity is not essential for the optimal
      expression of UL41 and ICP0.

PMID- 16095648
TI  - Coordinate induction of IFN-alpha and -gamma by SARS-CoV also in the absence of
      virus replication.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is an emerging infection
      caused by a novel coronavirus known as SARS-CoV, characterized by an over
      exuberant immune response with lung lymphomononuclear cells infiltration and
      proliferation that may account for tissue damage more than the direct effect of
      viral replication. This study is aimed at investigating the capability of SARS
      CoV to activate IFN-alpha and -gamma expression in lymphomonocytes (PBMC) from
      healthy donors, evaluating whether viral replication is necessary for this
      activation. RESULTS: SARS-CoV virus is able to induce both IFN-alpha and -gamma
      mRNA accumulation and protein release in a dose-dependent manner, MOI 10 being
      the most effective. The time course curve indicated that IFN-alpha mRNA induction
      peaked at 24 h.p.i,. whereas IFN-gamma mRNA was still increasing at 48 h.p.i.
      Released IFN (both types) reached a plateau after 24-48 h.p.i. and remained
      rather stable over a 5-day period. A transient peak of negative strand viral RNA
      was detected after 1-2 days of infection, but neither infectious virus progeny
      yield nor newly produced viral genomic RNA could be evidenced in infected
      cultures, even after prolonged observation time (up to 13 days). Cocultivation of
      PBMC with fixed SARS-CoV-infected Vero cells was even more efficient than
      exposure to live virus in eliciting IFN-alpha and -gamma induction. A combination
      of IFN-alpha and -gamma strongly inhibited SARS-CoV replication in Vero cells,
      while the single cytokines were much less effective. CONCLUSIONS: This study
      provides evidence that SARS-CoV is able to induce in normal PBMC a coordinate
      induction of IFN-alpha and -gamma gene expression. Virus replication is not
      necessary for IFN induction since efficient IFN expression could be obtained also
      by the cocultivation of normal PBMC with fixed SARS-CoV-infected cells.
      Concomitant activation of IFN-alpha and -gamma gene expression by SARS-CoV in
      vivo may be relevant for the pathogenesis of the disease, both for the possible
      involvement in immunomediated damage of the tissues and for the strong inhibition
      of SARS-CoV replication as a result of combined cytokine action.

PMID- 16095649
TI  - Gaze direction modulates visual aftereffects in depth and color.
AB  - Prior physiological studies indicate that gaze direction modulates the gain of
      neural responses to visual stimuli. Here, we test gaze modulation in the
      perceptual domain using color and depth aftereffects. After confirming retinotopy
      of the effects, we employed a balanced alternating adaptation paradigm
      (adaptation alternates between opponent stimuli) to demonstrate that opposite
      color and depth aftereffects can co-develop at the same retinal location for
      different gaze directions. The results provide strong evidence for (a) gaze
      modulation of aftereffects, (b) generality of gaze modulation across two visual
      attributes, and (c) perceptual correlates of the modulation of neural activity by
      gaze direction.

PMID- 16095650
TI  - Illusory volumes in human stereo perception.
AB  - Any complete theory of human stereopsis must model not only how the
      correspondences between locations in the two views are determined and the depths
      are recovered from their disparity, but also how the ambiguity arising from such
      factors as noise, periodicity, and large regions of constant intensity are
      resolved and missing data are interpolated. In investigating this process of
      recovering surface structure from sparse disparity information, using stereo
      pairs with sparse identifiable features, we made an observation that contradicts
      all extant models. It suggests the inadequacy of retinotopic representation in
      modeling surface perception in this stage. We also suggest a possible alternative
      theory, which is a minimization of the modulus of Gaussian curvature.

PMID- 16095651
TI  - Comparison of Harms tangent screen and search coil recordings in patients with
      trochlear nerve palsy.
AB  - Harms tangent screen, a subjective measurement method of three-dimensional
      binocular alignment, was compared with search coil recording. Twenty-three
      patients with unilateral trochlear nerve palsy were measured in nine gaze
      positions. The two methods correlated best for the horizontal gaze deviation, the
      vertical gaze deviation, and the vertical incomitance, but there was no
      correlation for the results of torsional incomitance. Using Harms tangent screen,
      torsional deviation underestimated the torsional incomitance measured by the
      search coils. Therefore, central torsional fusional mechanisms or alignment error
      in the Harms tangent screen are assumed.

PMID- 16095652
TI  - Chromatic assimilation measured by temporal nulling.
AB  - Chromatic assimilation is the shift in color appearance toward nearby light.
      Assimilation was measured using nearby light with time-varying chromaticity. This
      light induced time-varying assimilation within the test area. Assimilation was
      quantified by the amplitude of temporally varying test-area light--in counter
      phase to the induced assimilation--required to null the assimilation. Unlike
      previous studies of assimilation, observers here judged only the steadiness of
      the test area, not its color. The inducing light was varied in luminance,
      temporal frequency and chromaticity. The measured assimilation could not be
      explained by only optical factors affecting receptoral quantal absorption. This
      implies a neural process contributes to assimilation. The nulling measurements
      showed also that assimilation was not induced independently within the L/M- and S
      cone pathways.

PMID- 16095653
TI  - Delayed mfERG responses in myopia.
AB  - It has been suggested that changes in the multifocal electroretinogram (mfERG)
      responses in myopes are primarily due to the increased axial length that
      accompanies myopia development. We investigated the characteristics of mfERG
      responses between emmetropes and myopes and determined the contribution of axial
      length to the mfERG data in 30 subjects (10 emmetropes and 20 myopes) using VERIS
      I. The amplitude and implicit time of the first positive peak (P1) of the first
      order kernel were analyzed. We found that P1 implicit time in myopes was
      significantly longer by 1.3-3.1 ms than that of the emmetropes and this was not
      explained by the myopes having greater axial lengths than the emmetropes. Axial
      length contributed to 15% of the implicit time total variance while refractive
      error accounted for 27%. Delayed mfERG responses observed in myopes were not
      attributable to the anatomical change that accompanies myopia and may suggest
      underlying differences in retinal function that result from being myopic.

PMID- 16095654
TI  - Coordination of smooth pursuit and saccades.
AB  - Smooth pursuit and saccades are two components of tracking eye movements. Their
      coordination has usually been studied by investigating latencies of pursuit onset
      in response to a moving target appearing simultaneously with the disappearance of
      the stationary fixation target. The general finding from such studies has been
      that latencies of saccades and pursuit are different and reflect independent
      processes. We discuss several limitations of the used targets. In this paper, we
      study latencies of saccades and smooth pursuit in response to a moving target
      that overlaps in time with a pursued moving target. We find that saccades and
      pursuit changes are synchronized. Furthermore, pursuit changes are made fast.
      Directional changes occur almost entirely within the accompanying saccade. To
      explain the results we hypothesize a two-stage mechanism for the coordinated
      generation of saccades and pursuit.

PMID- 16095655
TI  - Biodegradation of petroleum hydrocarbons in an immobilized cell airlift
      bioreactor.
AB  - An "immobilized cell airlift bioreactor", was used for the aerobic bioremediation
      of simulated diesel fuel contaminated groundwater and tested with p-xylene and
      naphthalene in batch and continuous regimes. The innovative design of the
      experiments consists of two stages. At the first stage "immobilized soil
      bioreactor" (ISBR) was used to develop an efficient microbial consortium from the
      indigenous microorganisms, which exist in diesel fuel contaminated soil. The
      concept of ISBR relies on the entrapment of the soil particles into the pores of
      a semi-permeable membrane, which divides the bioreactor into two aerated and non
      aerated portions. The second stage involves inoculating the "immobilized cell air
      lift bioreactor" with the cultivated microbial consortia of the first stage.
      Immobilized cell airlift bioreactor has the same configuration as ISBR except
      that in this bioreactor instead of soil, microorganisms were immobilized on the
      fibers of the membrane. The performance of a 0.83 L immobilized cell airlift
      bioreactor was investigated at various retention time (0.5-6 h) and
      concentrations of p-xylene (15, 40 and 77 mg/L) and naphthalene (8, 15 and 22
      mg/L) in the continuous operation. In the batch regime, 0.9L bioreactor was
      operated at various biodegradation times (15-135 min) and concentrations of p
      xylene (13.6, 44.9 and 67.5 mg/L) and naphthalene (1.5 and 3.8 mg/L). Under the
      conditions of the complete biodegradation of p-xylene and naphthalene, the
      obtained volumetric biodegradation rates at biomass density of 720 mg/L were 15
      and 16 mg/L h, respectively.

PMID- 16095656
TI  - An analytical model of enterococci inactivation, grazing, and transport in the
      surf zone of a marine beach.
AB  - An analytical model of enterococci (ENT) concentrations in the surf zone of a
      long sandy beach is constructed considering the physical processes of dilution by
      rip currents and alongshore littoral drift, and the biological processes of
      inactivation and mortality by grazing. The solution is used to construct an
      expression for the length of shoreline adversely impacted by ENT from a point
      source. Two non-dimensional parameters are developed whose magnitude can be used
      to ascertain whether dilution, inactivation, or grazing is the dominant sink for
      ENT in the surf zone. The model is applied to beaches in southern California,
      USA. Model input parameters related to physical processes and inactivation are
      compiled from the literature. Laboratory experiments are conducted to determine
      grazing mortality rates of ENT (6.5 x 10(-6) s(-1)). Results indicate that at the
      field sites, between 1000 and 5000 m of shoreline are typically impacted by a
      continuous point source of ENT. Dilution is the primary cause of decline in ENT
      concentrations within the surf zone, with inactivation secondary and grazing
      tertiary. Results recommend strategic positioning of point sources and timing of
      effluent releases to take advantage of high dilution conditions. Our estimates
      for grazing mortality rates are within the same order of magnitude as some
      published inactivation rates, thus we cannot rule out the possibility that
      grazing is an important sink for ENT, especially in low dilution environments
      like enclosed bays.

PMID- 16095657
TI  - The prevalence and characterisation of Cryptosporidium spp. in beef abattoir
      water supplies.
AB  - The prevalence of Cryptosporidium spp. in 50 l samples of water used to wash beef
      carcasses at (a) an abattoir with a borehole water (BH) supply (n = 46) and (b)
      an abattoir with a river water (RW) supply (n = 48) was determined. In addition,
      a 100 l water sample and post-wash carcass samples (n = 24) were collected from
      the RW supply on a single day in July. Cryptosporidium spp. was detected in 0%
      and 26.1% of samples from the BH and RW supply abattoirs, respectively, with
      oocyst concentrations ranging from 0.02 to 8.6/l. Cryptosporidium spp. was not
      isolated from post-wash beef carcasses, while it was detected in water samples
      from that day at a concentration of 0.06 oocysts/l. The species of 3/5 isolates
      were identified as C. parvum, and the remaining were C. andersoni. This study has
      demonstrated that water used to wash beef carcasses can be contaminated with
      Cryptosporidium of human health importance and is a potential source of carcass
      contamination.

PMID- 16095658
TI  - Re-use of water treatment works sludge to enhance particulate pollutant removal
      from sewage.
AB  - This paper attempted to study the feasibility of reusing water treatment works
      sludge ("alum sludge") to improve particulate pollutant removal from sewage. The
      main issues focused upon were: (1) the appropriate dosage of the alum sludge, (2)
      the appropriate operating conditions, and (3) the possible mechanisms for
      enhancement by adding alum sludge. Actual alum sludge and sewage were applied to
      a series of jar tests conducted under various conditions. It has been found that
      both the SS and COD removal efficiencies could be improved by the addition of the
      alum sludge, which was mainly attributed to the removal of relatively fine
      particles with a size of 48-200 microm. The appropriate dosage of the alum sludge
      was determined to be 18-20 mg of Al/L. Increasing the mixing speed or reducing
      the floc size of the alum sludge enhanced the SS and COD removal and the
      dispersed alum sludge could remove particulate contaminants with smaller size
      than the raw sewage. ToF-SIMS evidence revealed that the aluminum species at the
      surface of the alum sludge were effectively utilized for improving the SS and COD
      removal. It was postulated that the sweep flocculation and/or the physical
      adsorption might play key roles in the enhancement of particulate pollutant
      removal from sewage.

PMID- 16095659
TI  - Effect of humic acids on heavy metal removal by zero-valent iron in batch and
      continuous flow column systems.
AB  - The effects of Aldrich humic acids (HA) on the removal of Zero-valent iron (ZVI)
      was investigated in laboratory systems. In batch, the removal rate of Zn and Ni
      (5 mg l(-1)) was, respectively, 2.8 and 2.4 times lower in the presence of HA (20
      mg l(-1)) than in the absence of HA, presumably due to the formation of HA-heavy
      metal complexes which prevented the removal reactions at the ZVI surface.
      Chromate removal was not affected. In a column test, two parallel systems were
      supplemented with a continuous input of simulated groundwater containing a
      mixture of the heavy metals Zn, Ni and Cr(VI) (5 mg l(-1) each), with or without
      HA (at 20 mg l(-1)). Initially, the two column systems efficiently (>90%) removed
      the heavy metals from the simulated groundwater. When the input heavy metal
      concentration was increased to 8-10 mg l(-1), a significant breakthrough of Ni
      and Zn, up to 80%, occurred in the column system fed with HA. Chromate and HA did
      not significantly break through. After 60 weeks, the effect of HA on leaching of
      the accumulated metals (approx. 2 mg g(-1)) was investigated. No significant
      leaching was observed. The results of this study suggest that the impact of
      dissolved organic matter on the efficiency and lifetime of a ZVI barrier for in
      situ removal of heavy metals should be considered in the design of the barrier.

PMID- 16095660
TI  - Iron type catalysts for the ozonation of oxalic acid in water.
AB  - Two iron catalysts (Fe(III) and Fe2O3/Al2O3) have been used in the ozonation of
      oxalic acid in water at pH 2.5. Percentage removals of oxalic acid were 1.8%, 7%
      and 30% corresponding to the non-catalytic, homogeneous (Fe(III)) and
      heterogeneous (Fe2O3/Al2O3) catalytic ozonations, respectively. Catalytic oxalic
      acid ozonation leads in all cases to total mineralization. The mechanism of
      ozonation likely develops through formation of iron-oxalate complexes that
      further react with ozone without the participation of hydroxyl radicals. Because
      of the stringent acidic conditions, some metal leaching has been observed and
      quantified in the heterogeneous process. In the homogeneous catalysis, the
      kinetics was found to be first order with respect to ozone and oxalic acid while
      for the heterogeneous catalysis, the kinetic order depends on the concentration
      of ozone in the gas fed. Thus, at ozone concentrations lower than 30 mg L(-1),
      the heterogeneous ozonation is between first and zero order with respect to both
      ozone and oxalic acid while at higher ozone gas concentrations, the kinetics was
      found to be first and zero order with respect to oxalic acid and ozone,
      respectively. This kinetics is supported through an Eley-Rideal mechanism that
      involves a surface reaction between non-adsorbed ozone and adsorbed oxalic acid.
      Apparent activation energies of the homogeneous and heterogeneous catalytic
      ozonations were found to be 18.2 and 13.6 kcal mol(-1), respectively.

PMID- 16095661
TI  - Phenolic wastewaters purification by thermal parametric pumping: modeling and
      pilot-scale experiments.
AB  - Thermal parametric pumping is a cyclic adsorptive process based on periodic
      changes in the bed temperature simultaneously with flow reversal. This is an
      innovative technology which may allow removing phenolic compounds from waste
      solutions to be recovered and recycled. The recovery and/or purification of
      liquid streams containing phenol and 4-nitrophenol by adsorptive parametric
      pumping was studied in this work. An automated parametric pumping pilot unit was
      operated in semi-continuous recuperative mode. The adsorbent used was the
      polymeric resin Sephabeads SP206 (Mitsubishi Kasei Corporation, Japan) and
      temperatures of the hot and the cold half-cycles were 333 and 293 K,
      respectively. Basic data were obtained from batch equilibrium experiments and
      fixed-bed adsorption. Different experimental conditions were run and two
      simplified models were used to simulate the results: an equilibrium model and a
      linear driving force (LDF) model. Experimental and simulated results using the
      LDF model were in quite good agreement. Purification levels below three orders of
      magnitude lower than the concentration of the feed solution were obtained for
      phenol and 4-nitrophenol.

PMID- 16095662
TI  - Wastewater sludge as a potential raw material for antagonistic fungus
      (Trichoderma sp.): role of pre-treatment and solids concentration.
AB  - Feasibility of production of antagonistic Trichoderma sp. conidial spores using
      wastewater sludge as a raw material employing different suspended solids
      concentration (10-50 g/l) was investigated in shake flasks. Maximum conidial
      spore count obtained for raw sludge was 1.98 x 10(4) CFU/ml, which was enhanced
      by sludge pre-treatments (alkaline and thermal alkaline). Conidial spore count
      ranging from 1.3 x 10(6) to 2.8 x 10(7) CFU/ml was observed for alkaline and
      thermal alkaline treated sludges. Optimal suspended solids concentration was 30
      g/l (10(7) CFU/ml) whereas, lower (<20 g/l) and higher (>30 g/l) solids
      concentration were less efficient. Thermal alkaline pre-treated sludge showed
      diauxic growth due to multiplicity of sludge biodegradability. A simple, modified
      CFU filtration technique was also developed for fungal spore assessment in
      sludge. Bioassay of fermented sludge against spruce budworm larvae showed
      entomotoxicity (15036 SBU/microl), on par with Bacillus thuringiensis
      biopesticides. This study successfully demonstrated potential of wastewater
      sludge as a raw material for production of value added product, aiding in sludge
      management and proliferation of eco-friendly and economical biocontrol agents.

PMID- 16095663
TI  - Characterization of sewage plant hydrocolloids using asymmetrical flow field-flow
      fractionation and ICP-mass spectrometry.
AB  - Asymmetrical flow field-flow fractionation (AF4) was applied to characterize
      aquatic colloids from biological sewage plants and to infer information of
      colloidal loads, sources, and sinks within the plants, resp. the colloidal
      interaction with the aqueous phase and the sewage sludge. To characterize the
      colloids further, especially the distributions of colloid associated heavy
      metals, the AF4 system was coupled to an inductively coupled plasma mass
      spectrometer (ICP-MS). The size distribution is determined by AF4 with UV
      absorbance and fluorescence detection after a calibration by monodisperse
      polystyrene sulfonate standards (PSS). Samples from different sewage plants and
      from different depths and locations within a plant were compared. The
      fulvic/humic acid fraction with a particle diameter d(p) < 10 nm appeared to be
      comparable in all samples and decreases only slightly along the plants, whereas
      larger colloids with d(p) > 10 nm almost completely passed into the sewage
      sludge. The concentrations of the initial colloidal heavy metals decreased along
      the plants.

PMID- 16095664
TI  - Suspended solids in Missouri reservoirs in relation to catchment features and
      internal processes.
AB  - Mean total suspended solids (TSS), in 135 Missouri reservoirs range from 1.2 to
      47 mg/l. The volatile (VSS) and non-volatile (NVSS) fractions range from 0.6 to
      9.6 mg/l and 0.5 to 37 mg/l, respectively. %NVSS is the larger fraction and
      declines through summer as %VSS increases. Suspended solids (particularly VSS)
      correlate with metrics of lake trophic state and are positively related with the
      proportion of cropland (%C, r = 0.69-0.74) in their catchments, negatively
      related with forest cover (r = -0.54 to -0.56), and weakly related with grassland
      (r < 0.31). Regressions including %C with dam height (representing morphometry)
      and flushing rate (representing hydrology), explain approximately 70% of cross
      system variation in TSS and 67% in VSS. Dam height and %C explain 57% of
      variation in NVSS. Residual analysis shows statewide models under-predict
      suspended solids in urban reservoirs. Effects of catchment features on summer TSS
      largely reflect internal plankton growth mediated by influent nutrients
      (affecting VSS) over direct sediment input (affecting NVSS).

PMID- 16095665
TI  - Degradation of zearalenone and ochratoxin A in three Danish agricultural soils.
AB  - Degradation of two mycotoxins: zearalenone (ZON) produced by species of Fusarium
      and ochratoxin A (OTA) produced by species of Penicillium were followed in pot
      experiments using agricultural topsoils from Danish experimental farms: a sandy
      soil, a sandy clay soil and a gyttja soil with a high content of silt.
      Experiments with unplanted soil and pots planted with barley were included. Soil
      samples were withdrawn during a period of 225 days and analysed for the content
      of OTA and ZON. The degradation of both toxins consisted of an initial fast
      degradation followed by a slower transformation step and was described well by a
      sum of two first-order kinetic equations. The decay first-order rate constants
      for the first step (k1) were in the range 0.73-2.91 d(-1) for OTA and 0.0612
      0.108 d(-1) for ZON, respectively. Half-lives (t0.5) for ZON using data from the
      first phase were between 6.4 and 11 days, whereas the half-lives for OTA were
      about 0.2-1 day. The slowest degradation was measured in soil rich in clay. After
      225 days, neither OTA nor ZON was detected in any of the soil types. Generally,
      the degradation of ZON and OTA was faster in planted soil than in unplanted soil,
      probably due to higher microbial activity. Due to the fast degradation of ZON and
      OTA in surface soil leaching as soluble substances appears to be limited.

PMID- 16095666
TI  - Size and XAD fractionations of trihalomethane precursors from soils.
AB  - Soil organic matter is an important source of allochthonous dissolved organic
      matter inputs to the Sacramento-San Joaquin Delta waterways, which is a drinking
      water source for 22 million people in California, USA. Knowledge of
      trihalomethane (THM) formation potential of soil-derived organic carbon is
      important for developing effective strategies for organic carbon removal in
      drinking water treatment. In this study, soil organic carbon was extracted with
      electrolytes (deionized H2O and Na- or Ca-based electrolytes) of electrical
      conductivity bracketing those found in Delta leaching and runoff conditions. The
      extracts were physically and chemically separated into different fractions:
      colloidal organic carbon (0.45-0.1 microm), fine colloidal organic carbon (0.1
      0.025 microm), and dissolved organic carbon (DOC) (<0.025 microm); hydrophobic
      acid (HPOA), transphilic acid, and hydrophilic acid. Two representative Delta
      soils, Rindge Muck (a peat soil) and Scribner Clay Loam (a mineral soil) were
      examined. Results showed that less than 2% of soil organic carbon was electrolyte
      extractable and heterogeneous organic fractions with distinct THM reactivity
      existed. Regardless of soil and electrolytes, DOC and HPOA fractions were
      dominant in terms of total concentration and THMFP. The amounts of extractable
      organic carbon and THMFP were dependent on the cation and to a lesser extent on
      electrical conductivity of electrolytes. Along with our previous study on
      temperature and moisture effects on DOC production, we propose a conceptual model
      to describe the impacts of agricultural practices on DOC production in the Delta.
      DOC is mainly produced in the surface peat soils during the summer and is
      immobilized by accumulated salt in the soils. DOC is leached from soils to
      drainage ditches and finally to the Delta channels during winter salt leaching
      practices.

PMID- 16095667
TI  - Increased thyroid volume and frequency of thyroid disorders signs in
      schoolchildren from nitrate polluted area.
AB  - Thyroid volume (ThV) and echogenicity by ultrasound were estimated in 324
      schoolchildren (aged between 10 and 13-years) from high nitrate area (HNA)
      located in agricultural lowland with high nitrate drinking water supply (51-274
      mg/l) from shallow wells. The data were compared to children of the same age from
      low nitrate area (LNA) consisting of 168 children from the neighboring area with
      very low nitrate (< 2 mg/l) drinking water and of 596 children from the city of
      Kosice located in a vicinity of LNA and also supplied by low nitrate water. Blood
      samples were obtained from 315 willing children from HNA and 109 children from
      LNA and the levels of thyrotropin (TSH), total thyroxine (TT4), free
      triiodothyronine (FT3) and thyroperoxidase antibodies (anti-TPO) in serum were
      determined. ThV (mean +/- SE) in 10-year (5.10 +/- 0.14 ml) and 13-year (5.97 +/-
      0.11 ml) old children from HNA was significantly higher than that in two groups
      of respective age from LNA, 4.58 +/- 0.17 (p < 0.02) and 5.23 +/- 0.15 ml (p <
      0.05), and from the city of Kosice, 4.77 +/- 0.10 ml (p < 0.05) and 4.87 +/- 0.1
      0ml (p < 0.0001). The frequency of hypoechogenicity in HNA was also significantly
      higher than that in pooled LNA plus Kosice, 13.7% vs. 4.7% (p < 0.01) in 10-year
      and 10.6% vs. 5.7% (p < 0.03) in 13-year, respectively. The frequency of TSH
      level in the range of subclinical hypothyroidism (> 4.0 mU/l) in pooled age
      groups from HNA was 13/324 (4.0%) and that of positive anti-TPO was 8/324 (2.5%),
      while no case of either increased TSH or positive anti-TPO was found in 109
      children from LNA. Finally, no differences in the levels of TT4 and FT3 were
      found between HNA and LNA. It was concluded that long-term exposure to high
      nitrate intake by drinking water and home made meals from local products results
      in increased thyroid volume and increased frequency of signs of subclinical
      thyroid disorders (thyroid hypoechogenicity by ultrasound, increased TSH level
      and positive anti-TPO).

PMID- 16095668
TI  - Contribution of an affect-associated gene to human longevity: prevalence of the
      long-allele genotype of the serotonin transporter-linked gene in Japanese
      centenarians.
AB  - Negative affect such as depression and anxiety has been reported to be associated
      with morbidity and mortality, and polymorphisms of the serotonin transporter
      (5HTT) gene may be associated with such affect disorders. Hypothesizing that 5HTT
      gene polymorphisms could influence human longevity via negative affect; we
      compared the polymorphic variation of the 5HTT gene between 265 Japanese
      centenarians and control subjects. In addition, we evaluated the relationships
      between the 5HTT genotype and the physical, cognitive, and biologic status of
      centenarians, as indicated by the Barthel Index, the Mini-Mental State
      Examination, and serum albumin concentration, respectively. The frequency of the
      l/l genotype and the l allele was significantly greater in centenarians than in
      younger control subjects, particularly women. A significant effect of the 5HTT
      genotype on serum albumin concentration was observed in both sexes. Although,
      there was sex optionality, the l allele may carry a longevity advantage possibly
      through behavioral mechanisms.

PMID- 16095669
TI  - Distribution of Cd, Zn, Cu and Fe among selected tissues of the earthworm
      (Allolobophora caliginosa) and Eurasian woodcock (Scolopax rusticola).
AB  - We have measured the concentrations of heavy metals in soils, earthworms and
      tissues of woodcocks in Quaderna Valley, northern Italy. The soil concentration
      of metals analysed in this research is consistent with data reported by other
      authors for uncontaminated or slightly contaminated soils. In earthworms, metals
      were mostly accumulated in the encapsulating chloragogenous tissue; the positive
      correlation between Cu concentration in the soil and in earthworms is noteworthy.
      Heavy metal distribution in the tissues of woodcock showed that Cd accumulation
      in the kidney was linked to the diet. Cu and Fe were preferentially concentrated
      in the liver and Zn in the testis. Kidney Cd and Zn concentrations were higher in
      adults than in juveniles. In addition, a main kidney metallothionein isoform,
      containing Cd and Zn, was isolated. In the kidney, Cd levels were linearly
      correlated with the concentration of metallothionein. Of the investigated metals,
      Cd raises the greatest concern, due to the increasing soil contamination by human
      activities.

PMID- 16095670
TI  - Predicting residential ozone deficits from nearby traffic.
AB  - Oxides of nitrogen in fresh traffic exhaust are known to scavenge ambient ozone.
      However, there has only been little study of local variation in ozone resulting
      from variation in vehicular traffic patterns within communities. Homes of 78
      children were selected from a sample of participants in 3 communities in the
      southern California Children's Health Study. Twenty-four hour ozone measurements
      were made simultaneously at a home and at a community central site monitor on two
      occasions between February and November 1994. Homes were geo-coded, and local
      residential nitrogen oxides (NOx) above regional background due to nearby traffic
      at each participant's home were estimated using a line source dispersion model.
      Measured home ozone declined in a predictable manner as modeled residential NOx
      increased. NOx modeled from local traffic near homes accounted for variation in
      ozone concentrations of as much as 17 parts per billion. We conclude that
      residential ozone concentrations may be over- or underestimated by measurements
      at a community monitor, depending on the variation in local traffic in the
      community. These findings may have implications for studies of health effects of
      traffic-related pollutants.

PMID- 16095671
TI  - Comparative field study on precipitation, throughfall, stemflow, fog water, and
      atmospheric aerosol and gases at urban and rural sites in Japan.
AB  - Precipitation collected by a wet-only sampler (WP), precipitation collected by a
      filtering-type bulk sampler (BP), throughfall (TF), stemflow (SF), fog water
      (FW), and atmospheric aerosol and gases were collected at two sites with
      different site classifications: an urban site (Mt. Rokko) and a rural site (Mt.
      Awaga) to investigate canopy-atmosphere interactions and to study the chemistry
      of precipitation in forested areas located in different atmospheric conditions.
      Compared to those at the rural site, the monthly volume-weighted pH values at the
      urban site were not significantly (p>0.05) different for WP, higher (p<0.05) for
      BP, not significantly (p> 0.05) different for TF, lower (p<0.01) for SF, and
      lower (p<0.01) for FW. The order of mean pH values at the urban site was
      FW<SF<WP<TF<BP. In contrast, the order at the rural site was FW<SF<BP<WP<TF.
      Concentrations of chemical species at the urban site were higher than those at
      the rural site in all samples and all chemical species. In particular, higher
      NO(3)(-) concentrations at the urban site were observed in all samples. The
      amount of dry deposition on leaves at the urban site was approximately 1.17 times
      larger than that at the rural site. The monthly net TF (=TF-BP) in autumn seemed
      to be larger than that in summer; this trend was remarkable in K(+). The monthly
      NO(3)(-) deposition in the net TF was larger at the urban site than at other
      parameters and at the rural site. The concentrations of chemical species in
      aerosol and gases that were measured near the central part of Kobe City were ca.
      3.4 times higher than those in the rural area. Mt. Rokko borders the central part
      of the city, which caused the concentrations at Mt. Rokko to be higher than those
      at Mt. Awaga. The deposition amounts at Mt. Rokko were larger than those at Mt.
      Awaga, which probably can be attributed to the higher concentrations of chemical
      species in atmospheric aerosol and gases.

PMID- 16095672
TI  - Particles and associated metals in road runoff during snowmelt and rainfall.
AB  - This study analysed road runoff in northern Sweden with respect to the
      concentrations of and the loads of particles in different size fractions (4-6, 6
      9, 9-15, 15-25, 25-40, and 40-120 mum) between a snowmelt period and a rainfall
      period, as well as during events within each period. There are also comparisons
      of the transport of different particle sizes between the two periods and during
      events within the periods and discussions on how different metals are associated
      with the varying particle sizes. The results showed, on average, eight times
      higher concentrations and five times higher loads of particles during the
      snowmelt period compared to the rain period for all particle size intervals.
      Using a t-test with 14 degrees of freedom, at a 90% and 95% confidence level, the
      mean- and the event mean concentrations of all particle size intervals were
      higher during the melt period compared to the rain period. Also, the particle
      concentrations for both periods decrease as the particle size increases. During
      the snowmelt and rainfall period, important factors influencing the
      concentrations and loads were the availability of material, the intensity of the
      lateral flow for the transport of the particles, and, additionally, for the rain
      period, the length of dry weather in between events. During the melt period,
      investigated particle sizes and TSS were highly correlated with total
      concentrations of Cd, Cu, Ni, Pb, and Zn. During the rain period, the
      correlations between total metal concentrations and the different particle sizes
      were not as significant.

PMID- 16095675
TI  - WITHDRAWN: Manuscript #2 (LEE): NIH conf on dietary supplements.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 16095676
TI  - Age-specific ovarian cancer incidence rate patterns in the United States.

PMID- 16095677
TI  - Intraperitoneal carboplatin infusion may be a pharmacologically more reasonable
      route than intravenous administration as a systemic chemotherapy. A comparative
      pharmacokinetic analysis of platinum using a new mathematical model after
      intraperitoneal vs. intravenous infusion of carboplatin--a Sankai Gynecology
      Study Group (SGSG) study.
AB  - OBJECTIVE: To clarify the pharmacological advantage of carboplatin-based
      intraperitoneal chemotherapy using the three-compartment mathematical model.
      METHODS: Eleven consecutive patients in one institution underwent intraperitoneal
      administration of carboplatin, and 11 consecutive patients in another institution
      received intravenous administration. Carboplatin (AUC=6 mg x min/ml) was diluted
      in 500 ml 5% glucose and administered either as an intraperitoneal bolus infusion
      or intravenous drip infusion during 1 h. Patients undergoing intravenous
      injection also received an infusion of 500 ml 5% glucose to obtain
      intraperitoneal samples. Intraperitoneal fluid and blood samples were obtained,
      immediately and 1, 2, 4, 8, 12, and 24 h after administration. The mathematical
      model consisting of a three-compartment model was applied to analyze the
      pharmacokinetics. The model was created with simultaneous differential equations
      and was solved by the Runge-Kutta method. RESULTS: The rate constants of platinum
      diffusion from the peritoneal cavity to serum, serum to peritoneal cavity, serum
      to peripheral space, peripheral space to serum, and elimination were 0.94+/-0.79
      (mean+/-SD), 1.28+/-2.50, 16.50+/-9.26, 0.99+/-0.62, and 4.14+/-1.45 (h-1),
      respectively. When the theoretical pharmacological concentration of platinum was
      calculated using this mathematical model, 24-h platinum AUC in the serum was
      exactly the same regardless of intraperitoneal or intravenous administration of
      carboplatin. However, the 24-h platinum AUC in the peritoneal cavity was
      approximately 17 times higher when carboplatin was administered by the
      intraperitoneal route. CONCLUSION: The present pharmacological analysis suggests
      that intraperitoneal infusion of carboplatin is feasible not only as an
      intraperitoneal regional therapy but also as a more reasonable route for systemic
      chemotherapy.

PMID- 16095678
TI  - Impaired female sexual behavior of rat offspring exposed to Solanum lycocarpum
      unripe fruits during gestation and lactation: lack of hormonal and fertility
      alterations.
AB  - Solanum lycocarpum St. Hil (Solanaceae) is an invasive and native shrub very
      common in the Brazilian savanna. It is well known that this plant contain
      steroidal glycoalkaloids that can be transformed into an intermediate for
      steroidal drugs production, like oral contraceptives. In this way, it is very
      possible that these glycoalkaloids and its aglycone, once in the body by
      ingestion of S. lycocarpum fruits, may act disrupting to the endocrine system.
      Rat offspring were exposed to S. lycocarpum unripe fruits (10% in the diet) from
      gestational day (GD) 06 to post-natal day (PND) 07. The female exposed offspring
      showed, at adult age (PND 100), impaired sexual behavior. However, the fecal
      hormonal metabolite levels, measured at PND 30, PND 60 and PND 90, and the
      fertility (PND 120) of male and female experimental offspring were normal. We can
      assume that the steroidal glycoalkaloids, solamargine and solasodine, present in
      the fruit, are degradated, once inside the organism, to the steroidal alkaloid
      solasodine, which may penetrate, by simple diffusion, the placental and/or the
      hematoencephalical barriers and impact the fetuses. Finally, S. lycocarpum fruit
      may act as phytohormones, promoting perhaps some neural alterations that at adult
      age may impair the sexual behavior of the experimental female without impairing
      the fertility and sexual hormone synthesis. These changes observed can be the
      direct consequence of the toxic actions of the steroidal alkaloid on the female
      offspring during fetal development.

PMID- 16095679
TI  - Equine blastocyst development after intracytoplasmic injection of sperm subjected
      to two freeze-thaw cycles.
AB  - This study was conducted to evaluate the effects of thawing, division into
      aliquots and refreezing on fertilizing capacity (ability to support embryo
      development after intracytoplasmic sperm injection; ICSI) of frozen stallion
      semen. Frozen semen from a fertile stallion was thawed, diluted 1:100 with
      freezing extender, and refrozen (2F treatment). Control semen was frozen only
      once. In vitro matured equine oocytes were injected with: (1) motile control
      spermatozoa; (2) motile 2F spermatozoa; (3) non-motile 2F spermatozoa; or (4) non
      motile 2F spermatozoa, followed by injection of sperm extract. Blastocyst
      development after ICSI was equivalent between control spermatozoa and motile 2F
      spermatozoa (27 and 23%, respectively). Blastocyst development after injection of
      non-motile 2F spermatozoa (13%) tended (P=0.07) to be lower than that for control
      spermatozoa. Injection of sperm extract into oocytes that received non-motile 2F
      spermatozoa resulted in a significant decrease in blastocyst development (to 2%)
      compared with injection of non-motile 2F spermatozoa alone. Spermatozoa from a
      subfertile stallion was similarly processed and used for ICSI; blastocyst
      development for both motile control (once frozen) spermatozoa and motile 2F
      spermatozoa was 9%. In conclusion, frozen stallion semen may be thawed, diluted,
      and refrozen without effect on the ability of motile spermatozoa to initiate
      embryo development after ICSI. Non-motile spermatozoa from reprocessed semen may
      also achieve embryo development after ICSI. To our knowledge, this is the first
      report evaluating the ability of refrozen spermatozoa to produce embryos by ICSI
      in any species.

PMID- 16095680
TI  - Continuous fetal heart rate monitoring during late gestation in cattle by means
      of Doppler ultrasonography: reference values obtained by computer-assisted
      analysis.
AB  - Continuous fetal heart rate (FHR) monitoring using transabdominal Doppler
      ultrasonography can be assumed to provide information about the viability of the
      bovine fetus during late gestation, as has been found in humans. To be able to
      recognize unfavourable fetal conditions, first the normal ranges of FHR
      parameters in cattle should be established. Therefore, in this study we aimed to
      determine the normal ranges of computerized FHR parameters, like basal fetal
      heart rate (BHR), number of accelerations and decelerations per hour and short
      and long term variation (STV and LTV) during the last 3 weeks before calving (n =
      21 cows). Each cow had one recording in each of three episodes of 7 days before
      parturition. As recording time in the cow is limited, we also studied whether
      these FHR parameters differ between recordings of 30 and 60 min duration (n = 31
      pairs of recordings). The outcomes of FHR recordings with a duration of 30 or 60
      min did not differ significantly, except for a higher percentage of signal loss
      in the 60 min recordings. Therefore, determination of normal ranges was performed
      in 30 min recordings. BHR decreased from 3 to 2 weeks (114 to 109 bpm; P <
      0.0001) before parturition and then remained constant until 2 days before
      calving. The mean number of accelerations per hour ranged between 4.4 and 5.0 h(
      1) and did not change significantly with time. Compared to 3 weeks before
      parturition, STV was significantly higher at 2 weeks (P < 0.05), but not at 1
      week before parturition (8.1, 10.0, and 9.2 ms, respectively). Changes in LTV
      showed a time course comparable to that of STV, but significance was not reached
      (51.4, 58.6, and 58.4 ms for respectively 3, 2 and 1 weeks before parturition).
      No decelerations were found during the period understudy. In conclusion, this
      study has provided normal ranges of bovine computerized FHR parameters during the
      last 3 weeks of gestation, allowing a comparison with data from cows with
      compromised gestations in future.

PMID- 16095681
TI  - Ultrasonic wave spectroscopy study of sugar oligomers and polysaccharides in
      aqueous solutions: the hydration length concept.
AB  - The determination of apparent persistence length and radius of gyration of
      maltodextrins in water is achievable through high-resolution ultrasonic
      spectroscopy measurements. Classical hydration number for those carbohydrates is
      characteristic of an apparent persistence degree of polymerisation of the
      polymer. A force-field based molecular modeling of a 10DP malto-oligomer allows
      measurement of the corresponding length for the lowest energetic conformation in
      solution. A good agreement between the apparent radii of gyration determined by
      this technique and the freely rotating polymer chain model is found with radii of
      gyration calculated from the intrinsic viscosity.

PMID- 16095682
TI  - Effects of mercuric ion on the conformation and activity of Penaeus Vannamei beta
      N-acetyl-d-glucosaminidase.
AB  - beta-N-acetyl-d-glucosaminidase (NAGase, EC.3.2.1.52), a composition of the
      chitinases, catalyzes the cleavage of N-acetylglucosamine polymers into N
      acetylglucosamine. In this paper, the effects of mercuric ion on the activity of
      NAGase from Penaeus vannamei for the hydrolysis of pNP-NAG have been studied. The
      results show that HgCl2 can lead to irreversible inactivation to this enzyme. The
      inactivation process follows a first-order reaction and the inactivation rate
      constants have been determined. The relationship between the inactivation rate
      constants and HgCl2 concentration has been studied and the result shows that only
      one molecule of HgCl2 binds to the enzyme molecule to lead the enzyme lose its
      activity. Moreover, the conformational changes of the enzyme inactivated by HgCl2
      were studied by following changes in the intrinsic fluorescence emission and
      ultraviolet absorption spectra.

PMID- 16095683
TI  - Mechanical properties of human stratum corneum: effects of temperature,
      hydration, and chemical treatment.
AB  - An in vitro mechanics approach to quantify the intercellular delamination energy
      and mechanical behavior of isolated human stratum corneum (SC) in a direction
      perpendicular to the skin surface is presented. The effects of temperature,
      hydration, and a chloroform-methanol treatment to remove intercellular lipids
      were explored. The delamination energy for debonding of cells within the SC layer
      was found to be sensitive to the moisture content of the tissue and to the test
      temperature. Delamination energies for untreated stratum corneum were measured in
      the range of 1-8J/m(2) depending on test temperature. Fully hydrated specimen
      energies decreased with increasing temperature, while room-humidity-hydrated
      specimens exhibited more constant values of 2-4J/m(2). Lipid-extracted specimens
      exhibited higher delamination energies of approximately 12J/m(2), with values
      decreasing to approximately 4J/m(2) with increasing test temperature. The peak
      separation stress decreased with increasing temperature and hydration, but lipid
      extracted specimens exhibited higher peak stresses than untreated controls. The
      delaminated surfaces revealed an intercellular failure path with no evidence of
      tearing or fracture of cells. The highly anisotropic mechanical behavior of the
      SC is discussed in relation to the underlying SC structure.

PMID- 16095684
TI  - Single molecule fluorescence studies of surface-adsorbed fibronectin.
AB  - The conformation of the extracellular matrix protein fibronectin plays a critical
      role in regulating cell function, including cell adhesion and migration. While
      average conformations of large ensembles of adhesion proteins have been
      previously measured, cells may sensitively respond to conformational outliers. We
      therefore applied both single molecule imaging and spectroscopy techniques to map
      a range of conformational states of individual fibronectin molecules adsorbed to
      glass, as well as to measure their conformational fluctuations in time. Single
      step photobleaching experiments confirmed single molecule sensitivity. Single
      molecule spectra showed fluctuations in the peak wavelength, both over a spatial
      ensemble of molecules and in a single molecule over time, most likely indicating
      the different conformational states fibronectin can assume upon surface
      adsorption. Single-pair fluorescence resonance energy transfer (FRET) revealed
      that a fraction of fibronectin molecules existed in conformations that allowed
      for energy transfer between the labeled cysteine residues of the two dimeric arms
      folded upon each other, and that fluctuations occurred in the FRET efficiency.
      Fluorescence polarization experiments identified two possible sources of FRET
      fluctuations: changes in fluorophore orientation and conformational fluctuations
      of fibronectin over a time scale of seconds.

PMID- 16095686
TI  - Reduced thrombogenicity of nitinol stents--in vitro evaluation of different
      surface modifications and coatings.
AB  - The material and the surface patterns of intravascular stents play a pivotal role
      in activating platelets and triggering adherence of inflammatory cells that
      consecutively leads to renarrowing caused by neointimal hyperplasia. To improve
      these features, besides mechanical and chemical modifications, ways of masking
      the stent by covering have been developed. In addition, polymer-coated stents are
      used as vehicle for local drug delivery. But as substances used for this
      application are described to possess an inflammatory potential, this aspect has
      to be evaluated. In the present study we compared different approaches to surface
      alterations applied to a nitinol stent design. Besides commonly used techniques
      like passivation and electropolishing, we evaluated coatings with heparin,
      aluminium and a polyurethane polymer regarding their thrombogenic and
      inflammatory characteristics. By weaving thin elastomer fibres a graft was
      generated. The previously described Chandler loop was used to simulate arterial
      flow conditions ex vivo using rotating PVC tubings filled with human blood. All
      stents received 120 min of blood contact. To determine thrombocyte activation and
      inflammatory reaction, the platelet count and levels of beta-TG, TAT and PMN
      elastase were assessed. Scanning electron microscopy was used to visualize the
      reactions. Mechanical polishing and passivation did not improve the stent surface
      characteristics while sandblasting, electropolishing and aluminium covering
      decreased activation of the coagulation cascade. In terms of thrombogenicity, the
      heparin coating had no beneficial effect. The lowest thrombogenic potential was
      found in the Polyurethane-coated stent group. All stents showed similar levels of
      polymorph nuclear granulocyte elastase except for the membrane design. While
      mechanical and chemical modifications are able to reduce thrombogenicity, coating
      with this particular polyurethane polymer seems to be superior to these
      approaches regarding the parameters assessed in this experimental setting. The
      Chandler loop is a valuable tool to test polymeric coatings ex vivo since these
      modifications may reduce drug performance by inducing inflammatory reaction
      themselves.

PMID- 16095685
TI  - Microintegrating smooth muscle cells into a biodegradable, elastomeric fiber
      matrix.
AB  - Electrospinning permits fabrication of biodegradable elastomers into matrices
      that can resemble the scale and mechanical behavior of the native extracellular
      matrix. However, achieving high-cellular density and infiltration with this
      technique remains challenging and time consuming. We have overcome this
      limitation by electrospraying vascular smooth muscle cells (SMCs) concurrently
      with electrospinning a biodegradable, elastomeric poly(ester urethane)urea
      (PEUU). Trypan blue staining revealed no significant decrease in cell viability
      from the fabrication process and electrosprayed SMCs spread and proliferated
      similar to control unprocessed SMCs. The resulting SMC microintegrated PEUU
      constructs were cultured under static conditions or transmural perfusion. Higher
      cell numbers resulted with perfusion culture with 131% and 98% more viable cells
      versus static culture at days 4 and 7 (p<0.05). Fluorescent imaging and
      hematoxylin and eosin staining further illustrated high cell densities integrated
      between the elastomeric fibers after perfusion culture. SMC microintegrated PEUU
      was strong, flexible and anisotropic with tensile strengths ranging from 2.0 to
      6.5 MPa and breaking strains from 850 to 1,700% dependent on the material axis.
      The ability to microintegrate smooth muscle or other cell types into a
      biodegradable elastomer fiber matrix embodies a novel tissue engineering approach
      that could be applied to fabricate high cell density elastic tissue mimetics,
      blood vessels or other cardiovascular tissues.

PMID- 16095687
TI  - Bioluminescence imaging of nuclear calcium oscillations in intact pancreatic
      islets of Langerhans from the mouse.
AB  - The stimulus-secretion coupling for insulin secretion by pancreatic beta cells in
      response to high glucose involves synchronic cytosolic calcium oscillations
      driven by bursting electrical activity. Calcium inside organelles can regulate
      additional functions, but analysis of subcellular calcium signals, specially at
      the single cell level, has been hampered for technical constrains. Here we have
      monitored nuclear calcium oscillations by bioluminescence imaging of targeted
      aequorin in individual cells within intact islets of Langerhans as well as in the
      whole islet. We find that glucose generates a pattern of nuclear calcium
      oscillations resembling those found in the cytosol. Some cells showed synchronous
      nuclear calcium oscillations suggesting that the islet of Langerhans may also
      regulate the activation of Ca(2+)-responsive nuclear processes, such as gene
      transcription, in a coordinated, synchronic manner. The nuclear Ca(2+)
      oscillations are due to bursting electrical activity and activation of plasma
      membrane voltage-gated Ca(2+) channels with little or no contribution of calcium
      release from the intracellular Ca(2+) stores. Irregularities in consumption of
      aequorins suggests that depolarization may generate formation of steep Ca(2+)
      gradients in both the cytosol and the nucleus, but further research is required
      to investigate the role of such high [Ca(2+)] microdomains.

PMID- 16095688
TI  - Release and sequestration of Ca2+ by a caffeine- and ryanodine-sensitive store in
      a sub-population of human SH-SY5Y neuroblastoma cells.
AB  - We have used single cell fluorescence imaging techniques to examine the role that
      ryanodine receptors play in the stimulus-induced Ca(2+) responses of SH-SY5Y
      cells. The muscarinic agonist methacholine (1mM) resulted in a Ca(2+) signal in
      95% of all cells. Caffeine (30 mM) however stimulated a Ca(2+) signal in only 1
      7% of N-type (neuroblastic) cells within any given field. The caffeine response
      was independent of extracellular Ca(2+), regenerative in nature, and abolished in
      a use-dependent fashion by ryanodine. In caffeine-responsive cells, the magnitude
      of the methacholine-induced Ca(2+) signal was inhibited by 75.07 +/- 5.51% by
      pretreatment with caffeine and ryanodine, suggesting that the caffeine-sensitive
      store may act as a Ca(2+) source after muscarinic stimulation. When these data
      were combined with equivalent data from non-caffeine-responsive cells, the degree
      of apparent inhibition was significantly reduced. In contrast, after store
      depletion by caffeine, the Ca(2+) signal induced by 55 mM K(+) was potentiated
      2.5-fold in the presence of ryanodine, suggesting that the store may act a Ca(2+)
      sink after depolarisation. We conclude that a caffeine- and ryanodine-sensitive
      store can act as a Ca(2+) source and sink in SH-SY5Y cells, and that effects of
      the store can become obscured if data from caffeine-insensitive cells are not
      excluded.

PMID- 16095689
TI  - Calcium and glial cell death.
AB  - Calcium (Ca2+) homeostasis is crucial for development and survival of virtually
      all types of cells including glia of the central nervous system (CNS).
      Astrocytes, oligodendrocytes and microglia, the major glial cell types in the
      CNS, are endowed with a rather sophisticated array of Ca2+-permeable receptors
      and channels, as well as store-operated channels and pumps, all of which
      determine Ca2+ homeostasis. In addition, glial cells detect functional activity
      in neighbouring neurons and respond to it by means of Ca2+ signals that can
      modulate synaptic interactions. Like in neurons, Ca2+ overload resulting from
      dysregulation of channels and pumps can be deleterious to glia. In this review,
      we summarize recent advances in the understanding Ca2+ homeostasis in glial
      cells, the consequences of its alteration in cell demise as well as in
      neurological and psychiatric disorders that experience glial cell loss.

PMID- 16095690
TI  - Adverse prognostic impact of CD36 and CD2 expression in adult de novo acute
      myeloid leukemia patients.
AB  - BACKGROUND AND OBJECTIVES: A consecutive series of acute myeloid leukemias (AML)
      patients was analyzed in conditions which reduce the inter-assay variations (the
      same flow cytometer, the same observers and the same panel of monoclonal
      antibodies) in order to investigate the prognostic information provided by flow
      cytometry. DESIGN AND METHODS: Two hundred and sixty-six bone marrow (BM) samples
      from 326 patients enrolled in the LMA-99 protocol from the CETLAM group were
      studied by multiparametric flow cytometry. Immunophenotyping studies were
      performed on erythrocyte-lysed BM samples. Antigen expression of leukemic cells
      was analyzed using triple stainings with fluorochrome-conjugated combinations of
      monoclonal antibodies. RESULTS: CD2 was positive in 21 cases (8%); an associated
      inv(16) was detected in eight CD2+ cases (38%). Two-year overall survival (OS)
      rate for CD2+/inv(16)+ patients was 75%, whereas it was 0% for CD2+/inv(16)-
      patients and 47% for CD2- patients (p=0.0001). CD36 was expressed in 37% of
      patients (n=98). Two-year leukemia-free survival (LFS) rate was 34% for CD36+
      patients and 55% for CD36- patients (p=0.001). In the multivariate analysis, CD2+
      (RR=8.4; p=0.0001) and adverse karyotype (RR=10.2; p=0.0001) were associated with
      a lower CR rate, CD36+ (RR=1.5; p=0.03), CD2+ (RR=2; p=0.04) and adverse
      karyotype (RR=4; p=0.0001) were associated with a lower OS and CD36+ (RR=2;
      p=0.002) and adverse karyotype (RR=3.5; p=0.005) predicted a lower LFS.
      CONCLUSIONS: CD2+ patients had a very poor OS when CD2/inv(16)+ cases were
      excluded. CD36 and CD2 expression at diagnosis can provide prognostically
      important information in adult de novo AML.

PMID- 16095691
TI  - Genotoxicity evaluation of acute doses of endosulfan to freshwater teleost Channa
      punctatus (Bloch) by alkaline single-cell gel electrophoresis.
AB  - The Indian freshwater air-breathing teleost fish Channa punctatus (Bloch) was
      exposed to acute concentrations of the organochlorine pesticide endosulfan. In
      flow-through bioassays the 24, 48, 72, and 96 h LC(50) values were estimated as
      19.67, 12.95, 10.15, and 7.75 ppb, respectively. DNA damage (single-strand
      breaks) was also studied in gill and kidney tissues at single-cell levels in the
      specimens, exposed to different acute doses of endosulfan, by applying single
      cell gel electrophoresis or comet assay. Dose-dependent responses were observed
      in DNA damage in both tissues. A comparison of DNA damage in both tissues at
      different doses indicated that the gill cells were more sensitive to the
      pesticide exposure than the kidney cells. This study explored the utility of the
      comet assay for in vivo laboratory studies using fish for screening the genotoxic
      potential of various agents.

PMID- 16095692
TI  - Acute effect of single-dose cadmium treatment on lipid peroxidation and
      antioxidant enzymes in ovariectomized rats.
AB  - We investigated the acute effect of single-dose cadmium (Cd) treatment on lipid
      peroxidation and antioxidant enzymes in liver and kidney of rats following an
      ovariectomy operation. Twenty-eight female Wistar albino rats were used and were
      divided into four groups: I, control (n=7); II, cadmium (Cd, n=7); III,
      ovariectomized (Ovx, n=7); and IV, ovariectomized+cadmium (Ovx-Cd, n=7). Fourteen
      of the rats were ovariectomized. Twelve weeks later, cadmium chloride (CdCl(2), 5
      mg/kg) was administered i.p. as a single dose to the Cd and Ovx-Cd groups. Twenty
      four hours after the injection, all rats were sacrificed and had their liver and
      kidney tissues removed for the measurement of superoxide dismutase (SOD),
      catalase (CAT), and malondialdehyde (MDA) levels. SOD activity showed a
      significant decrease (P<0.001) in both organs of Ovx and Cd rats in comparison to
      controls. CAT activity was significantly decreased (P<0.01) in the liver of Ovx
      and Cd groups but not in the kidneys of both groups compared to control values.
      MDA concentrations were higher (P<0.05) in both organs of Ovx and Cd rats than
      those values observed in the control group. Similar patterns of changes were
      observed in the Ovx-Cd rats, but the increase in the MDA levels and the decrease
      in the antioxidant enzymes for the Ovx-Cd group were higher than those of the Ovx
      and Cd groups. Based on the data, it can be stated that cadmium increases the
      effect of ovariectomy on lipid peroxidation, impairs the antioxidant defense
      system, and induces oxidative stress.

PMID- 16095693
TI  - Oxidative damage induced in brains and livers of mice by landfill leachate.
AB  - The effects of the Xingou municipal landfill leachate on levels of thiobarbituric
      acid reactive substances (TBARS) and the activities of Cu,Zn-superoxide dismutase
      (Cu,Zn-SOD), Se-dependent glutathione peroxidase (Se-dependent GPx), and catalase
      (CAT) were investigated in brains and livers of Kunming albino mice of both
      sexes, using chemical oxygen demand (COD(Cr)) as a measure of leachate
      concentration. The results show that leachate caused lipid peroxidation and
      change of antioxidative status in brains and livers of mice. There was a sex
      difference in the response of antioxidative status, and female mice were more
      sensitive than male mice. Exposure to leachate at all concentrations tested
      caused significant increases of TBARS levels in brains and livers from mice of
      both sexes. For brains, Cu,Zn-SOD and Se-dependent GPx activities were
      significantly increased at high concentration (COD(Cr) 240 mg/L) for male mice,
      but the activities of both antioxidative enzymes were significantly increased at
      low concentration (COD(Cr) 60 mg/L) and decreased at high concentration (COD(Cr)
      240 mg/L) for female mice; CAT activities remained unchanged for male mice and
      were significantly decreased for female mice at high concentration (COD(Cr) 240
      mg/L). For livers, Cu,Zn-SOD and Se-dependent GPx activities were significantly
      increased at high concentrations (COD(Cr) 120 and 240 mg/L) for male mice, but
      the activities of both antioxidative enzymes were significantly increased at low
      concentration (COD(Cr) 30 or 60 mg/L) and decreased at high concentration
      (COD(Cr) 240 mg/L) for female mice; CAT activities were significantly increased
      for male mice at all concentrations tested and decreased for female mice at high
      concentrations (COD(Cr) 120 and 240 mg/L). These results suggest that leachate
      exposure can cause oxidative damage on brains and livers of mice. The results
      also suggest that leachate might induce toxicity in mammals by the free-radical
      damage mechanism.

PMID- 16095694
TI  - The smell of danger: a behavioral and neural analysis of predator odor-induced
      fear.
AB  - The odors of predators used in animal models provide, in addition to electric
      footshock, an important means to investigate the neurobiology of fear. Studies
      indicate that cat odor and trimethylthiazoline (TMT), a synthetic compound
      isolated from fox feces, are often presented to rodents to induce fear-related
      responses including freezing, avoidance, stress hormone and, in some tests, risk
      assessment behavior. Furthermore, we report that different amounts of cat odor
      impregnated on small-, medium-, or large-sized cloths impact the display of fear
      related behavior when presented to rats. That is, rats exposed to a large cat
      odor containing cloth exhibit an increase in fear behavior, particularly
      freezing, which remains at high levels in habituation tests administered over a
      period of 7 days. The large cloth also induces a long-lasting increase in
      avoidance behavior during repeated habituation and extinction tests. A review of
      the brain regions involved in predator odor-induced fear behavior indicates a
      modulatory role of the medial amygdala, bed nucleus of the stria terminalis, and
      dorsal premammillary nucleus. In addition, the basolateral amygdala is involved
      in fear behavior induced by cat odor but not TMT, and the central amygdala does
      not appear to play a major behavioral role in predator odor-induced fear. Future
      research involving the use of predator odor is likely to rapidly expand knowledge
      on the neurobiology of fear, which has implications for understanding fear
      related psychopathology.

PMID- 16095695
TI  - Early life genetic, epigenetic and environmental factors shaping emotionality in
      rodents.
AB  - Childhood trauma is known to increase risk for emotional disorders and addiction.
      However, little is currently understood about the neurodevelopmental basis of
      these effects, or how genetic and epigenetic factors interact with the
      environment to shape the systems subserving emotionality. In this review, we
      discuss the use of rodent models of early life emotional experience to study
      these issues in the laboratory and present some of our pertinent findings. In
      rats, postnatal maternal separation can produce lasting increases in emotional
      behavior and stressor-reactivity, together with alterations in various brain
      neurotransmitter systems implicated in emotionality, including corticotropin
      releasing factor, serotonin, norepinephrine, and glutamate. Genetic differences
      between inbred mouse strains have been exploited to further study how maternal
      behavior affects emotional development using techniques such as cross-fostering
      and generation of inter-strain hybrids. Together with our own recent data, the
      findings of these studies demonstrate the pervasive influence of maternal and
      social environments during sensitive developmental periods and reveal how genetic
      factors determine how these early life experiences can shape brain and behavior
      throughout life.

PMID- 16095696
TI  - Role of nitric oxide in brain regions related to defensive reactions.
AB  - Nitric oxide synthase (NOS) positive neurons are located in most brain areas
      related to defensive reactions, including the dorsolateral periaqueductal grey
      (dlPAG). NOS inhibitors injected into this structure induce anxiolytic-like
      responses whereas NO donors promote flight reactions. Intra-dlPAG administration
      of carboxy-PTIO, a NO scavenger, or ODQ, a soluble guanylate cyclase inhibitor,
      produced anxiolytic-like effects on rats exposed to the elevated plus-maze (EPM).
      A double-staining experiment using NADPHd histochemistry and c-Fos
      immunohistochemistry in rats exposed to a cat or to the EPM showed increased
      activation of NO producing neurons in the dlPAG, paraventricular and lateral
      nuclei of hypothalamus and dorsal raphe nucleus. Cat exposure also increased
      activation of NOS neurons in the medial amygdala, dorsal pre-mammillary nucleus
      and bed nucleus of stria terminalis. Local infusion into the dlPAG of a glutamate
      NMDA-receptor antagonist (AP7) or a benzodiazepine agonist (midazolam) completely
      prevented the flight reactions induced by intra-dlPAG administration of SIN-1, a
      NO donor. The responses were also inhibited by the 5-HT2A/C agonist DOI but not
      by a 5-HT1A agonist. These results suggest a modulatory role for NO on brain
      areas related to defensive reactions, probably by interacting with glutamate,
      serotonin and/or GABA-mediated neurotransmission.

PMID- 16095697
TI  - Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral
      and cognitive functioning in human offspring.
AB  - Teratological investigations have demonstrated that agents that are relatively
      harmless to the mother may have significant negative consequences to the fetus.
      Among these agents, prenatal alcohol, nicotine or cannabis exposure have been
      related to adverse offspring outcomes. Although there is a relatively extensive
      body of literature that has focused upon birth and behavioral outcomes in
      newborns and infants after prenatal exposure to maternal smoking, drinking and,
      to a lesser extent, cannabis use, information on neurobehavioral and cognitive
      teratogenic findings beyond these early ages is still quite limited. Furthermore,
      most studies have focused on prenatal exposure to heavy levels of smoking,
      drinking or cannabis use. Few recent studies have paid attention to low or
      moderate levels of exposure to these substances. This review endeavors to provide
      an overview of such studies, and includes animal findings and potential
      mechanisms that may explain the mostly subtle effects found on neurobehavioral
      and cognitive outcomes. It is concluded that prenatal exposure to either maternal
      smoking, alcohol or cannabis use is related to some common neurobehavioral and
      cognitive outcomes, including symptoms of ADHD (inattention, impulsivity),
      increased externalizing behavior, decreased general cognitive functioning, and
      deficits in learning and memory tasks.

PMID- 16095698
TI  - Stress-induced enhancement of fear learning: an animal model of posttraumatic
      stress disorder.
AB  - Fear is an adaptive response that initiates defensive behavior to protect animals
      and humans from danger. However, anxiety disorders, such as Posttraumatic Stress
      Disorder (PTSD), can occur when fear is inappropriately regulated. Fear
      conditioning can be used to study aspects of PTSD, and we have developed a model
      in which pre-exposure to a stressor of repeated footshock enhances conditional
      fear responding to a single context-shock pairing. The experiments in this
      chapter address interpretations of this effect including generalization and
      summation or fear, inflation, and altered pain sensitivity. The results of these
      experiments lead to the conclusion that pre-exposure to shock sensitizes
      conditional fear responding to similar less intense stressors. This sensitization
      effect resists exposure therapy (extinction) and amnestic (NMDA antagonist)
      treatment. The pattern predicts why in PTSD patients, mild stressors cause
      reactions more appropriate for the original traumatic stressor and why new fears
      are so readily formed in these patients. This model can facilitate the study of
      neurobiological mechanisms underlying sensitization of responses observed in
      PTSD.

PMID- 16095699
TI  - Glucocorticoid inhibits the human pro-interleukin lbeta gene (ILIB) by decreasing
      DNA binding of transactivators to the signal-responsive enhancer.
AB  - Elucidating the role of glucocorticoid in regulating gene expression is crucial
      to developing effective strategies against inflammatory diseases such as
      arthritis. In this report we demonstrate that glucocorticoid inhibits
      transcription directed by the IL-lbeta gene (IL1B) upstream induction sequence
      (UIS) enhancer, and to a much lesser extent by the tissue-specific basal
      promoter. Within the enhancer, three transcription factor binding sites,
      previously demonstrated by us to be important for the induction of IL1B by
      lipopolysaccharide, are now shown to be directly inhibited by the synthetic
      glucocorticoid, dexamethasone. We also previously showed that one of these sites
      could bind a novel STAT-like factor, while the other two bound heterodimers
      containing NF-IL6(C/EBPbeta). Although it has been reported by others that NF-IL6
      homodimers can interact with glucocorticoid receptor (GR) to enhance
      transcription of the alpha1-acid glycoprotein gene, it now appears that
      glucocorticoid represses DNA binding of NF-IL6 heterodimers as well as the novel
      STAT-like factor to the critical sites within the IL1B UIS. Thus, GR likely
      disrupts the DNA binding capability of critical IL1B factors via transrepression.

PMID- 16095700
TI  - Higher-order aberrations in eyes with irregular corneas after laser refractive
      surgery.
AB  - PURPOSE: To investigate the distribution of the eye's higher-order aberrations in
      postoperative laser refractive surgery patients with visual complaints and highly
      irregular corneal shapes. DESIGN: Retrospective case-control study. PARTICIPANTS:
      Thirty-three symptomatic postoperative LASIK and/or photorefractive keratectomy
      eyes with subjective visual complaints not corrected by spectacles more than 6
      months after surgery are compared with 46 normal preoperative and 46 asymptomatic
      successful postoperative conventional LASIK eyes. METHODS: Postoperative wave
      aberrations were measured for each patient using a Shack-Hartmann wavefront
      sensor (Zywave, Bausch & Lomb, Rochester, NY) over a 6-mm pupil. These
      measurements were averaged across patients with similar corneal topographic
      diagnoses (central islands, decentered ablations, a new group termed baby
      bowties, and irregularly irregular corneas). MAIN OUTCOME MEASURES: Higher-order
      aberrations and corneal topography. RESULTS: The average (+/-1 standard
      deviation) higher-order root-mean-square (rms) wavefront error values (third,
      fourth, and fifth orders) for the symptomatic patients was 1.31+/-0.58 microm.
      This was an average of 3.46 times greater than the average magnitude of normal
      preoperative eyes (mean rms, 0.38+/-0.14 microm), and an average of 2.3 times
      greater than the average magnitude of asymptomatic successful postoperative
      conventional LASIK eyes (mean rms, 0.58+/-0.21 microm) over a 6-mm pupil. Higher
      order rms wavefront error increased with pupil size, roughly doubling for every
      millimeter of increasing pupil diameter. On average, eyes with central islands (n
      = 6) had the most vertical coma (Z3(-1); mean, -1.35+/-0.43 microm). Eyes with
      central islands and decentered ablations (n = 2) also had elevated amounts of
      spherical aberration (Z4(0); means of 0.83+/-0.11 microm and 0.69+/-0.29 microm,
      respectively) compared with successful postoperative LASIK eyes (mean of 0.42+/
      0.20 microm). Eyes with a topographic central baby bowtie demonstrated the most
      secondary astigmatism (Z4(2) and Z4(-2); mean rms, 0.56+/-0.17 microm; n = 3),
      despite the lowest average higher-order rms (mean, 0.84+/-0.05 microm) among
      symptomatic topographic subgroups. Eyes with irregularly irregular corneas had a
      mean higher-order rms of 1.10+/-0.39 mum. CONCLUSIONS: Symptomatic postoperative
      laser refractive surgery patients with irregular corneas have higher-order
      aberrations that are 2.3 to 3.5 times greater than asymptomatic postoperative
      LASIK and normal preoperative eyes, respectively. The higher-order aberrations
      seem to correlate with corneal topography.

PMID- 16095701
TI  - Pyodermatitis-pyostomatitis vegetans of the eyelids case report and review of the
      literature.
AB  - OBJECTIVES: To present the first reported case of eyelid involvement in
      pyodermatitis-pyostomatitis vegetans (PDPSV) leading to the diagnosis of
      ulcerative colitis, and to review the literature. DESIGN: Interventional case
      report. METHODS: A 29-year-old man presented with a 4-week history of severe
      bilateral upper and lower eyelid margin ulceration and pustules unresponsive to
      topical and systemic broad-spectrum antibiotic treatment. Further questioning
      revealed the existence of skin and oral lesions. MAIN OUTCOME MEASURES: Clinical
      course, histological findings, and response to treatment. RESULTS: The
      histological and immunofluorescence studies were suggestive of PDPSV. Colonoscopy
      showed significant chronic active ulcerative colitis. Treatment with systemic
      steroids and sulfasalazine resulted in complete resolution of eyelid, oral, and
      skin lesions. However, stopping the steroids resulted in recurrence of eyelid and
      oral lesions and required recommencement of treatment. CONCLUSION: It is
      important to be familiar with this pustular skin condition, as correct diagnosis
      may lead to the diagnosis of inflammatory bowel disease. Although periocular
      involvement is probably rare, the combined typical skin and oral lesions and the
      characteristic histological and immunofluorescence tests should suggest the
      correct diagnosis.

PMID- 16095702
TI  - Intraocular foreign body injuries during Operation Iraqi Freedom.
AB  - OBJECTIVE: To evaluate the number of intraocular foreign body (IOFB) injuries
      that occurred in Operation Iraqi Freedom, and to determine the cause of injury,
      the type of foreign body, and the associated injuries to other body systems.
      DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS:
      Fifty-five United States military personnel with an IOFB injury during Operation
      Iraqi Freedom. INTERVENTION: Pars plana vitrectomy, foreign body removal, and
      additional surgical procedures as the clinical situation dictated. MAIN OUTCOME
      MEASURES: Cause of injury, size of corneal/scleral laceration, number of foreign
      bodies, type of foreign body, time to foreign body removal, visual acuity, number
      of enucleations, and injuries to other body systems. RESULTS: The foreign body
      was caused by a propelled explosive in 20 patients (36%) and a nonpropelled
      explosive in 31 patients (56%), and the cause of the foreign body was not known
      in 4 patients (7%). The size of the laceration of the cornea and/or sclera
      averaged 5.4 mm (range, 0.2-18). There were an average of 1.7 foreign bodies in
      the injured eye (range, 1-6). The size of those foreign bodies measured ranged
      from <1 mm to 12 x 14 mm. The most common type of foreign body was metal (68%),
      followed by glass (14%), stone/cement (14%), bone (5%), and cilia (3%). The time
      from injury to foreign body removal averaged 20.6 days (range, 0-90). No cases of
      endophthalmitis were seen. The most common associated injury was to the upper
      extremity, face, lower extremity, and neck. CONCLUSIONS: Unlike trauma in the
      civilian sector, IOFB injuries in a military setting tend to be caused by
      explosive devices, which often result in multiple foreign bodies and simultaneous
      injuries to other body systems. Because of the lack of availability of specialty
      care in the combat theater, there is often a delay in removal of the foreign
      body.

PMID- 16095703
TI  - Idiopathic orbital hemorrhage related to the inferior rectus muscle: a rare cause
      for acute-onset diplopia and unilateral proptosis.
AB  - PURPOSE: To report 6 patients with spontaneous orbital hemorrhage in relation to
      the inferior rectus muscle. DESIGN: Retrospective observational case series.
      PARTICIPANTS: Six patients with acute onset orbital pain, diplopia, and proptosis
      referred to the orbital clinic at the Royal Victorian Eye and Ear Hospital,
      January 1995 through December 2004. METHODS: Review of clinical history, imaging
      studies, and follow-up. MAIN OUTCOME MEASURES: Resolution of proptosis and
      diplopia and imaging studies of the orbit, including computed tomography (CT),
      magnetic resonance imaging (MRI), or both. RESULTS: Six patients (4 men, 2 women;
      mean age, 68 years) were referred with acute onset of unilateral proptosis and
      diplopia. None of the patients had a history of bleeding disorder. Visual acuity
      and intraocular pressure were normal; 3 patients showed marked limitation in
      upgaze on the affected side. Imaging studies of the orbit by CT, MRI, or both
      showed inferior orbital hemorrhage either within (4 patients) or adjacent to (2
      patients) the inferior rectus muscle, possibly within the muscular sheath.
      Symptoms resolved completely in all but 1 patient, who had persistent diplopia in
      extreme upgaze. Follow-up CT, MRI, or both showed complete resolution in 3
      patients and mild persistent inferior rectus muscle thickening in 2 patients.
      CONCLUSIONS: Acute onset proptosis and diplopia may be secondary to spontaneous
      orbital hemorrhage within the inferior rectus muscle or its sheath with no other
      orbital or systemic pathologic features. Symptoms resolved spontaneously over the
      course of days to weeks, and orbital imaging showed complete resolution or mild
      persistent enlargement of the muscle without significant symptoms.

PMID- 16095704
TI  - Intraocular lens implantation after atopic cataract surgery decreases incidence
      of postoperative retinal detachment.
AB  - PURPOSE: To investigate the efficacy of intraocular lens (IOL) implantation in
      reducing the incidence of postoperative retinal detachment after cataract surgery
      in patients with atopic dermatitis. DESIGN: Retrospective review. PARTICIPANTS:
      One hundred sixty-nine eyes of 126 patients who underwent cataract surgery for
      atopic cataract were followed for more than 1 year. None of the eyes previously
      had a retinal detachment or retinal detachment surgery. METHODS: The eyes were
      divided into 132 eyes of 95 patients with an IOL implantation (IOL group) and 37
      eyes of 31 patients without an IOL implantation (aphakia group). The
      postoperative visual acuity and incidence of postoperative retinal detachment
      were compared between the 2 groups. The effects of the location of the causative
      retinal breaks, intraoperative posterior capsule rupture, and postoperative
      posterior capsulotomy on the incidence of retinal detachments were evaluated.
      MAIN OUTCOME MEASURES: The postoperative corrected visual acuity, incidence of
      postoperative retinal detachment, and influence of intraoperative posterior
      capsule rupture on the retinal detachment. RESULTS: The final visual acuity was
      better than or equal to 20/20 in 128 eyes (97.0%) of the IOL group and in 29 eyes
      (78.4%) of the aphakia group (P = 0.0007). Retinal detachment after an
      uncomplicated cataract surgery occurred in 3 eyes (2.3%) of the IOL group and in
      8 eyes (25.8%) of the aphakia group (P<0.0001, Mantel-Cox). Two of 3 eyes (66.7%)
      in the IOL group and 1 of 8 eyes (16.7%) in the aphakia group that later
      developed a retinal detachment had an intraoperative posterior capsule rupture.
      Posterior capsulotomy by yttrium-aluminum-garnet laser did not seem to alter the
      incidence of postoperative retinal detachment in either the IOL (2.0%) or the
      aphakia group (25.0%). CONCLUSIONS: The rate of postoperative retinal detachment
      in eyes with IOL and no intraoperative posterior capsule rupture seems to be low.
      Intraocular lens implantation with capsular bag fixation may reduce the incidence
      of postoperative retinal detachment triggered by lens surgery for atopic
      cataract.

PMID- 16095705
TI  - Tear film tests in Parkinson's disease patients.
AB  - OBJECTIVE: Parkinson's disease (PD) has both motor and nonmotor features.
      Parkinson's disease patients are prone to dry eye due to both autonomic
      dysfunction and motor symptoms affecting blinking. This study was conducted to
      investigate the changes in tear functions in PD patients. DESIGN: Nonrandomized,
      prospective, clinical study. PARTICIPANTS: Fifty-six eyes of 56 consecutive
      patients with PD were studied. Thirty-six eyes of age-matched non-PD patients
      without pathology affecting tear tests were examined as control subjects.
      INTERVENTION: Modified Hoehn-Yahr (H-Y) scale, blink rate (BR), and tear tests
      were examined. MAIN OUTCOME MEASURES: Modified H-Y scale, BR, dry eye assessment
      questionnaire, meibomian gland evaluation, tear meniscus height, tear breakup
      time, fluorescein stain, rose bengal stain, Schirmer's test, and phenol red
      thread test. RESULTS: Overall tear function abnormalities were significantly more
      common in PD patients (P = 0.001, Mann-Whitney U test). Each test was found to be
      significantly disturbed in PD patients relative to controls (P<0.05, Mann-Whitney
      U test). Each PD patient had at least 1 abnormal test. Overall tear function
      abnormalities as assessed by the total abnormal test count correlated with the H
      Y score (P<0.001, Spearman rho correlation). Parkinson's disease patients' mean
      BR (12.7+/-7.42 per minute) was significantly less than the controls' (21.8+/
      7.37) (P<0.01, Student's t test). The abnormality in each tear test, except those
      for meibomian gland function and tear meniscus height, was significantly related
      to the H-Y scores (P<0.05, chi2 linear-by-linear association). CONCLUSION: The
      results of this study indicate that PD is associated with disturbances in tear
      function. With the exception of meibomian gland disease and tear meniscus height,
      the tests were found to have a linear association with the H-Y scale, which may
      be attributed to associated dysfunctions of PD.

PMID- 16095706
TI  - Relationship of dissociated optic nerve fiber layer appearance to internal
      limiting membrane peeling.
AB  - PURPOSE: The dissociated optic nerve fiber layer (DONFL) appearance features
      numerous arcuate striae after vitrectomy for idiopathic epiretinal membrane or
      macular hole. We studied the relation between the DONFL appearance and internal
      limiting membrane (ILM) peeling and performed static microperimetry to explore
      the possible mechanisms underlying the DONFL appearance. DESIGN: Prospective
      cohort study. PARTICIPANTS: Ninety-five eyes of 88 consecutive patients
      undergoing vitrectomy for idiopathic macular hole. METHODS: Vitrectomy and gas
      tamponade were performed with or without ILM peeling. All eyes were examined
      postoperatively using fundus photography with blue filters. Static microperimetry
      was performed in 31 eyes with a clearly visible DONFL appearance. MAIN OUTCOME
      MEASURE: The postoperative incidence of the DONFL appearance on blue-filtered
      fundus photographs. The secondary outcome measure included the microperimetry
      threshold value in the arcuate striae and the surrounding normal retina within
      the papillomacular bundle. RESULTS: On blue-filtered photographs, 46 (62.2%) of
      74 eyes with ILM peeling exhibited the DONFL appearance, compared with 0 (0%) of
      21 eyes without ILM peeling (P = 0.0002). The area of the DONFL appearance was
      limited to the area of ILM peeling. There was no difference in the microperimetry
      threshold value between the arcuate striae and the surrounding normal retina (P =
      0.9312). CONCLUSION: The present study indicates that the DONFL appearance might
      be related to ILM peeling and is not associated with the loss of optic nerve
      fibers. These results are consistent with the suggestion that the DONFL
      appearance might be caused by cleavage of the optic nerve fiber bundles due to
      damage to the Muller cells, which are in close contact with the ILM and act to
      maintain the close proximity of the nerve fiber bundles.

PMID- 16095707
TI  - Variation of 24-hour intraocular pressure in healthy individuals: right eye
      versus left eye.
AB  - PURPOSE: An assumption for the one-eye therapeutic trial of ocular hypotensive
      drugs is the symmetrical variation of intraocular pressure (IOP) between the two
      eyes. We evaluated whether or not 24-hour variations of IOP in the two eyes are
      similar in healthy individuals. DESIGN: Experimental study with human subjects.
      PARTICIPANTS: Ninety-one healthy individuals. METHODS: We reviewed bilateral IOP
      data collected from 38 younger (18-25 years) and 53 older (40-74 years)
      experimental subjects housed for 24 hours in a sleep laboratory. Intraocular
      pressure was measured every 2 hours using a pneumatonometer in the sitting and
      supine positions during the 16-hour diurnal/wake period and in the supine
      position during the 8-hour nocturnal/sleep period. Measurements were always taken
      first in the right eye. For each age group, the two eyes' means, peaks, troughs,
      and ranges of IOP during office hours, the diurnal period, the nocturnal period,
      and the 24-hour period were compared. The coefficient of determination was used
      to examine the strength of association between the right and left IOPs. MAIN
      OUTCOME MEASURES: Bilateral IOP. RESULTS: For each age group, the profiles of IOP
      variations were similar in the two eyes with either the habitual body positions
      (diurnal sitting and nocturnal supine) or the 24-hour supine position. Mean,
      peak, and trough IOPs in the right eye were slightly higher than those in the
      left eye during the defined periods. There was no difference in the IOP range,
      except for the supine IOP in the younger group during the diurnal period. Cosine
      fits of the 24-hour supine IOP indicate no difference in the estimated phase
      timing or the 24-hour variation between the two eyes. Coefficients of
      determination for single pairs of right and left IOPs were in the range of 0.311
      to 0.741. CONCLUSION: Variations of 24-hour IOP in the right and left eyes are
      similar. However, because the strength of association between the two eyes is
      only moderate, it may be difficult to perform a one-eye therapeutic trial using
      single pairs of right and left eye IOP measurements.

PMID- 16095709
TI  - Physiological and genetic analyses of aluminium tolerance in rice, focusing on
      root growth during germination.
AB  - Aluminium (Al) ion limits root growth of plants in acidic soils, and rice
      exhibits the highest level of Al-tolerance among graminous crops. To elucidate Al
      tolerance mechanisms in rice, response to Al was compared between rice (Oryza
      sativa L., cv. Nipponbare) and wheat (Triticum aestivum L., cv. ET8), focusing on
      seminal root growth at seedling stage and germination stage. At seedling stage,
      rice and wheat were similarly sensitive to Al in both dose- and time-dependent
      manner during a 24-h Al exposure. On the contrary, at germination stage, rice was
      more tolerant to Al than wheat, and wheat roots displayed the loss of plasma
      membrane integrity more extensively than rice. A rice mutant exhibiting Al
      hypersensitivity at germination stage was obtained by screening 42,840 R2 progeny
      derived from the regenerated R0 plants of Nipponbare and thereafter confirmation
      of the mutant phenotype in R3 progeny. At germination stage, root growth of the
      mutant was strongly inhibited in the presence of Al but not in the absence of Al.
      However, at seedling stage, root growth of the mutant and wild type was similarly
      tolerant to Al. Taken together, we conclude that rice possesses Al-tolerant
      function that is under genetic control and specifically operates for root growth
      at germination stage, making rice more tolerant to Al than wheat.

PMID- 16095708
TI  - Outcomes of iodine 125 plaque radiotherapy after initial observation of suspected
      small choroidal melanomas: a pilot study.
AB  - PURPOSE: To determine the visual and survival outcomes for patients undergoing
      plaque radiotherapy of suspected small choroidal melanomas after observation for
      growth in a pilot study. DESIGN: Noncomparative interventional case series.
      PARTICIPANTS: Forty-five patients with suspected small choroidal melanomas who
      were seen at the Bascom Palmer Eye Institute between 1974 and 2001 and had iodine
      125 (I125) plaque radiotherapy between 1991 and 2002. METHODS: Patients with
      suspected small choroidal melanomas were monitored by clinical examination,
      photography, and echography. When the melanoma grew or developed orange pigment,
      patients were treated with I125 plaque radiotherapy. Outcomes included visual
      acuity, ocular complications, tumor dimensions, metastasis, and death. MAIN
      OUTCOME MEASURE: Melanoma-specific mortality. RESULTS: In our pilot study, 1
      patient died from metastatic melanoma. One patient developed metastatic disease
      and is still alive. One patient developed marginal tumor recurrence after
      treatment and after enucleation was performed. Globe conservation was achieved in
      97.8% of patients. In patients with tumor margins >2 mm from the optic nerve,
      vision was preserved with less than a doubling of the visual angle (within
      approximately 2 Snellen lines of preoperative acuity) in 90.6% (29/32) of
      patients at 1 year postoperatively, 65.6% (21/32) at 2 years, and 52.2% (12/23)
      in the long term (4-11 years). CONCLUSIONS: Five-year melanoma-specific mortality
      after I125 plaque radiotherapy of suspected small choroidal melanomas was 3.9%
      (95% confidence interval, 0%-11.2%). This information can be used to counsel
      patients with small suspected choroidal melanomas and to compare with other
      treatment modalities.

PMID- 16095710
TI  - Nanosized flower-like ZnO synthesized by a simple hydrothermal method and applied
      as matrix for horseradish peroxidase immobilization for electro-biosensing.
AB  - Nanosized flower-like ZnO was synthesized by a simple hydrothermal method which
      is a convenient, environment friendly, inexpensive and efficient process. Raman
      spectroscopy, X-ray diffraction (XRD) and scanning electron microscope (SEM) were
      used to confirm the material structure and the crystallite microstructure. Then
      ZnO was dispersed in the chitosan solution to form a ZnO/chitosan composite
      matrix for the fabrication of H2O2 biosensor. This composite combined the
      advantages of inorganic species (ZnO) and organic polymer (chitosan). The
      parameters affecting the fabrication and experimental conditions of biosensors
      were optimized. Using hydroquinone as the mediator, the biosensor showed a fast
      response of less than 5s with the linear range of 1.0x10(-5) to 1.8x10(-3) M H2O2
      with a correlation coefficient of 0.995 (n=20). The detection limit of the sensor
      was found to be 2.0 microM, based on a signal-to-noise ratio of 3. The biosensor
      exhibited satisfactory reproducibility and stability and retained about 78% of
      its original response after 40 days storage in a phosphate buffer at 4 degrees C.

PMID- 16095711
TI  - Comparison of water-soluble and exchangeable forms of Al in acid forest soils.
AB  - Soil acidification promotes Al release from minerals and parent bedrocks; it also
      affects Al mobilization and speciation. Speciation of KCl extractable and water
      extractable Al in forest soils was done by means of HPLC/IC method. Species Al3+
      were the most abundant Al forms in the KCl extracts (around 93%). Prevailing Al
      forms (more than 70%) in aqueous extracts were Al(X)1+, [i.e., Al(OH)2+,
      Al(SO4)+, AlF2+, Al(oxalate)+, Al(H-citrate)+, etc.] species. It is assumed that
      most of KCl and water-extractable Al is bound in soil sorption complex (i.e.,
      highly dispersed colloidal fraction of the soil solid phase creating negative
      charge) where majority of Al exists in the form of Al3+ species. The ECEC values,
      total carbon content and parameters related to soil organic matter composition (N
      and S content) have apparent effect on Al speciation. The most toxic Al3+ species
      are more concentrated in the B horizons compared to the A and E horizons. Aqueous
      extracts simulate Al release to soil solution under normal conditions; it can
      thus exhibit the actual Al toxicity. On the other hand, KCl extraction describes
      a potential threat for case of strong disturbance of natural soil conditions.

PMID- 16095712
TI  - Factors controlling spatial distribution of soil acidification and Al forms in
      forest soils.
AB  - Soil acidification and Al release in forest soils is controlled by a number of
      factors, like acid deposition, forest type, parent rock, altitude, etc. This
      paper studies the principal stand factors affecting spatial distribution of the
      content of KCl-extractable Al (Al(KCl), mainly exchangeable), Na4P2O7-extractable
      Al (Al(Na4P2O7), mainly organically bound), and other soil characteristics
      related to acidification in surface organic (O) and subsurface mineral (B)
      horizons in the Jizera Mountains region. Geostatistical methods were exploited.
      The highest Al(KCl) contents in the O horizons were related to high S and N
      content, low pH and low Ca and Mg content in soil. Liming decreased Al(KCl)
      contents in the O horizons. Al(Na4P2O7) in the O horizons was more abundant under
      spruce than under beech; in both horizons it was increased on the immission clear
      cut areas populated by grass. Surface horizons are more sensitive to external
      influence (acid deposition, liming) and their spatial variation is stronger. In
      the mineral horizons, the effect of pedogenetic processes is more important. The
      effect of stand factors on Al behaviour is complex and often indirect, mediated
      for example by organic matter or soil reaction. It is difficult to clearly
      distinguish the effects of the particular factors.

PMID- 16095713
TI  - Therapeutic role of mitoxantrone in multiple sclerosis.
AB  - Mitoxantrone is approved by several health authorities for treatment of active
      forms of relapsing-remitting or secondary progressive multiple sclerosis (SPMS).
      This review provides an outline on relevant preclinical as well as clinical
      studies, places mitoxantrone in the context of other therapeutic approaches
      against multiple sclerosis (MS), and discusses relevant side effects. The current
      knowledge of the putative mechanisms of action of the compound is discussed.

PMID- 16095714
TI  - Ion channels and intracellular signaling proteins as potential targets for novel
      therapeutics for addictive and depressive disorders.
AB  - Modern neuroscience is placing increased emphasis on understanding how the
      activity of ion channels and intracellular molecules in the central nervous
      system affect behavior. An improved understanding of the brain and the biological
      bases of conditions such as addictive and depressive disorders is important
      because it should ultimately enable the design of innovative treatments for these
      conditions. The development of rational therapies that are based on knowledge of
      what is different about the addicted or depressed brain would be an important
      advance. Here, we describe how multidisciplinary studies that combine numerous
      approaches (behavioral analysis, physiology, molecular biology, and genetic
      engineering) have begun to provide important advances that have helped to
      establish causal relationships between the pathophysiology of these conditions
      and behavior. This type of work has identified classes of molecules on the
      outside of cells (receptors and ion channels) that receive signals from other
      cells and initiate cellular events that have short-term effects on the neurons.
      It has also identified other classes of molecules that are inside of cells
      (signal transduction molecules) that can have immediate effects on cell function
      (e.g., ion channel phosphorylation), as well longer term effects (alterations in
      protein expression) that affect the ways in which neurons function within
      circuits. Innovative treatments that block, negate, or even reverse the
      extracellular or intracellular neuroadaptations resulting from exposure to drugs
      of abuse or stress might be more effective than current therapies because they
      directly target the molecular processes that cause maladaptive behaviors.

PMID- 16095715
TI  - Marking multi-channel silicon-substrate electrode recording sites using
      radiofrequency lesions.
AB  - Silicon-substrate multi-channel electrodes (multiprobes) have proven useful in a
      variety of electrophysiological tasks. When using multiprobes it is often useful
      to identify the site of each channel, e.g., when recording single-unit activity
      from a heterogeneous structure. Lesion marking of electrode sites has been used
      for many years. Electrolytic, or direct current (DC) lesions, have been used
      successfully to mark multiprobe sites in rat hippocampus [Townsend G, Peloquin P,
      Kloosterman F, Hetke JF, Leung LS. Recording and marking with silicon
      multichannel electrodes. Brain Res Brain Res Protoc 2002;9:122-9]. The present
      method used radio-frequency (rf) lesions to distinctly mark each of the 16
      recording sites of 16-channel linear array multiprobes, in chinchilla inferior
      colliculus. A commercial radio-frequency lesioner was used as the current source,
      in conjunction with custom connectors adapted to the multiprobe configuration. In
      vitro bench testing was used to establish current-voltage-time parameters, as
      well as to check multiprobe integrity and radio-frequency performance. In in vivo
      application, visualization of individual-channel multiprobe recording sites was
      clear in 21 out of 33 sets of collicular serial-sections (i.e., probe tracks)
      obtained from acute experimental subjects, i.e., maximum post-lesion survival
      time of 2h. Advantages of the rf method include well-documented methods of in
      vitro calibration as well as low impact on probe integrity. The rf method of
      marking individual-channel sites should be useful in a variety of applications.

PMID- 16095716
TI  - Isolectin-IB 4 as a vascular stain for the study of adult neurogenesis.
AB  - It has been proposed that new neurons in the adult brain might preferentially
      develop in the immediate vicinity of existing vasculature, an area that has been
      referred to as a "vascular niche". The most common method for identifying neurons
      that arise as the result of mitotic activity is to label them with the thymidine
      analogue bromodeoxyuridine (BrdU), and a nuclear marker for mature neurons
      (NeuN). Unfortunately, commercially available forms of NeuN and the vasculature
      stain, RECA-1, are incompatible, as both antibodies are raised in the same
      species. This technical limitation has impeded the analysis of the relationship
      between new neurons and existing vasculature. In the present work we show that
      Isolectin-IB 4, a 114 k Da protein isolated from the seeds of the African legume,
      Griffonia simplicifolia, can be used to identify vasculature in conjunction with
      both NeuN and BrdU immunohistochemistry. Isolectin-IB 4 serves as an easy to use
      and robust marker for obtaining spatial information regarding the proximity of
      new neurons to vasculature in the mammalian brain.

PMID- 16095717
TI  - Self-inactivating lentiviruses: versatile vectors for quantitative transduction
      of cerebellar granule neurons and their progenitors.
AB  - Cerebellar granule neurons (CGNs) undergo a well-defined, intrinsic
      differentiation program that is recapitulated in vitro. Thus, homogeneous
      cultures of CGNs provide an excellent opportunity to define the mechanisms
      underlying their development. The ability to alter endogenous gene expression in
      CGNs on a population-wide basis would greatly facilitate the elucidation of these
      events. In the present study, we show that self-inactivating lentiviruses
      efficiently infect both dividing progenitors and post-mitotic CGN cultures in a
      quantitative manner without altering their cellular properties. The time course
      for protein expression was biphasic for both types of cultures, with the first
      peak occurring during the initial infection period. Thus, lentiviruses can
      express proteins in CGNs both acutely and on a long-term basis to study
      developmental and other processes continuously over an extended time period.
      These vectors also infected CGNs in cerebellar slice preparations. In addition,
      lentiviruses harboring a transgene for the mouse GABA(A) receptor alpha6 subunit
      promoter recapitulated the differentiation-dependent expression of this gene in
      CGN cultures. Self-inactivating lentiviruses are extremely versatile vectors that
      offer important advantages for studies of protein function and gene regulation.
      The ability to alter protein function on a global scale in CGN cultures permits
      biochemical assessment of its impact on mRNA and protein populations, as well as
      on protein--protein and protein--DNA interactions. Further, integrated
      lentiviruses can be used to study chromatin-dependent promoter regulation and
      transcription factor interactions in CGNs over time in a facile manner.

PMID- 16095718
TI  - Matching geometry and stimulation parameters of electrodes for deep brain
      stimulation experiments--numerical considerations.
AB  - Deep brain stimulation, the electric stimulation of basal ganglia nuclei, is a
      treatment for movement disorders such as Parkinson's disease. The underlying
      mechanisms are studied in animals, e.g. rodents. Designs and materials of
      commercially available microelectrodes, as well as experimentally applied driving
      signals vary tremendously. We used finite integration modeling to compare the
      electric field and current density distributions induced by various electrodes.
      Current density or field strength "hot spots", which are located particularly at
      sites of high curvature and material interfaces coincided with corrosion and
      erosion at poles and insulation, respectively, as shown by scanning electron
      microscopy of stainless steel electrodes. Cell constants, i.e. geometry factors
      relating the electrode impedance to the specific medium conductivity, were
      calculated to determine the electrode voltage for a given stimulation current.
      Nevertheless, for electrodes of the same cell constant but of different geometry,
      current and field distributions may be very dissimilar. We found geometry
      dependent limiting values of the stimulation current, above which electric tissue
      damage may occur. These values limit the reach of the stimulation signal for a
      given electrode geometry. Also, electrode geometries determine the shape of the
      stimulated tissue volume. This study provides tools for choosing the most
      appropriate geometry for targeting different-sized brain areas.

PMID- 16095719
TI  - Isolation of the gene encoding the bovine neonatal Fc receptor.
AB  - The role of an IgG-Fc receptor (FcRn) that resembles a class I MHC Ag in
      transporting IgGs through epithelial cells was recently shown in selected
      species. Here we report our preliminary characterization of a clone encoding the
      alpha chain of the bovine FcRn from a BAC library. The recombinant BAC DNA was
      digested, analyzed by Southern blot hybridization and a bovine FcRn positive 9 kb
      long fragment was subcloned and partially sequenced. The exon/intron organization
      of the bovine FcRn alpha chain gene was deduced by comparison with its cDNA
      sequence. The sequence revealed a similar organization to the human and mouse
      FcRn alpha chain genes. The bovine FcRn alpha chain gene has acquired several
      repetitive sequences in its 5'-flanking region, including multiple SINE and LINE
      elements. Potential binding sites for transcription factors within the 5'
      flanking sequence were identified using TESS and TFSEARCH programs. The 5'
      flanking region of the bFcRn alpha chain gene was analyzed for its ability to
      directly express the luciferase reporter gene in bovine mammary gland epithelial
      cells. Transient transfection of a luciferase construct revealed that there was
      promoter activity in the region -1787 to +92 of the 5'-flanking sequence.

PMID- 16095720
TI  - Identification and expression of Toll-like receptors 1-10 in selected bovine and
      ovine tissues.
AB  - Members of the Toll-like receptor (TLR) family are vital to immune function
      through the sensing of pathogenic agents and initiation of an appropriate immune
      response. More specifically, tissue and cell specific TLR expression patterns
      have been correlated with the ability to respond to various pathogenic
      challenges. Bovine sequence exists for 4 of the 10 human TLR Reference Sequences
      and no ovine TLR sequence has been reported. The main goal of this study was to
      determine if homologues of human TLRs 1-10 exist within the cattle and sheep.
      Subsequent to this, quantitative real time PCR assays were to be developed to
      produce transcript expression profiles in cattle skin and sheep gut-associated
      lymphoid tissue, as these epithelial tissues are the primary sites of
      host/pathogen interactions for numerous pathogens. Our findings show that
      homologues of human TLRs 1-10 do indeed exist within both cattle and sheep, with
      respective bovine and ovine homologues sharing at least 95% nucleotide sequence
      identity and 83-90% identity to the corresponding human Reference Sequences.
      Conservation of the amino acid sequence between homologous ruminant and human
      TLRs ranged between 84 and 97%. Quantitative real time PCR (qPCR) assays
      confirmed expression of all 10 TLRs within ovine jejunum, Peyer's patch and
      mesenteric lymph nodes. While in bovine skin all TLRs apart from TLR6 were
      detected. The most abundant TLR transcripts within the ovine jejunum were TLRs 3,
      5 and 6, while TLRs 6, 7 and 10 were abundant in both ovine Peyer's patch and
      mesenteric lymph node. In bovine skin TLRs 2 and 7 were most abundant. In all
      tissues tested TLR4 expression was at the lower limit of detection.

PMID- 16095722
TI  - Prostate cancer-induced immunodysfunction: a lesson from organ cultures.

PMID- 16095723
TI  - Identification of differentially expressed genes in the developing mouse inferior
      colliculus.
AB  - Although injured neurons of inferior colliculus (IC) display a robust axonal
      outgrowth through a lesion site at postnatal day six (P6) in vitro, and are
      capable to re-innervate their target cells, injured neurons from P10 IC are
      unable to regenerate their axons across the lesion site. This axonal regenerative
      failure has been attributed to an increase of expression of inhibitory molecules
      in endogenous tissue, during development. As a first step to identify such
      inhibitory molecules, the present study reports the isolation of molecules
      differentially expressed in the IC during development. A two-directional (forward
      and backward) suppression subtractive hybridization (SSH) was performed on IC
      tissue between P6 and P10 stages. One hundred cDNAs from P6 (P6-P10) and 200
      cDNAs from P10 (P10-P6)-subtracted libraries were randomly sequenced. A dot-blot
      screening of sequenced cDNAs revealed the differential expression for the
      majority of these cDNAs at their respective developmental stage. Then, the
      analysis of sequenced clones showed that P6 library was highly enriched in
      molecules expressed early in the development, such as GAP43 or vimentin proteins.
      By contrast, the P10 library contained mostly molecules expressed at later stages
      of development in the central nervous system, such as myelin-related proteins.
      Our results show that SSH is a suitable method for identifying differentially
      expressed genes in the developing IC. In addition, these results provide a
      foundation for further studies dealing with molecules involved in the IC
      development before and at the onset of hearing, some of which being probably
      involved in the axonal outgrowth mechanism.

PMID- 16095724
TI  - Spontaneous remyelination following prolonged inhibition of alpha4 integrin in
      chronic EAE.
AB  - Inhibition of alpha(4)beta(1) integrin blocks immune cell influx into the CNS
      providing benefit to patients with multiple sclerosis and in animal model
      systems. We have used this mechanism to examine whether the presence of
      inflammatory cells suppresses spontaneous myelin repair in experimental
      autoimmune encephalomyelitis. We observed (1) 87% of plaques showed remyelination
      after 40 days of treatment; (2) myelin repair occurred in half of the total
      lesion area; (3) half of the animals regained motor function. There was no
      significant repair or gain of motor function in vehicle-treated animals.
      Therefore, prolonged inhibition of CNS inflammation, in the absence of targeted
      myelin repair, facilitates mechanisms of spontaneous remyelination.

PMID- 16095725
TI  - Acute ileal inflammatory cytokine response induced by irradiation is modulated by
      subdiaphragmatic vagotomy.
AB  - Neural involvement plays a role in the genesis of the peripheral inflammatory
      process that contributes to the irradiation intestinal disorders. However, little
      is known about the role of vagus nerve in modulating inflammatory process in rat.
      Here, we have shown that the NF-kappaB activation was consistent with the acute
      overexpression of pro-inflammatory cytokines (IL- 1beta, TNF-alpha, IL-6) at 3,
      6, and 12 h induced by whole-body irradiation (8 Gy). Subdiaphragmatic vagotomy
      reduced NF-kappaB activation and cytokine transcription in the early period post
      irradiation. In contrast, vagotomy amplified overexpression of irradiation
      induced anti-cytokines (IL-10, IL-1Ra) and of receptors involved in anti
      inflammatory effects (IL- 1RII, TNFRII). These results show that the vagus nerve
      is a pro-inflammatory pathway in early irradiation-induced intestinal
      inflammation.

PMID- 16095726
TI  - Leptomeningeal cells activate microglia and astrocytes to induce IL-10 production
      by releasing pro-inflammatory cytokines during systemic inflammation.
AB  - The leptomeninges covering the surface of the brain parenchyma play the physical
      role at the cerebrospinal fluid-blood barrier. We report here that leptomeningeal
      cells may transduce peripheral proinflammatory signals to the central anti
      inflammatory response through the activation of glial cells in the brain
      parenchyma. After adjuvant injection, both microglia and astrocytes in the
      cerebral cortex localized in the proximity of the leptomeninges were activated.
      The protein levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10
      (IL-10) in the cortical extracts were significantly increased at different time
      after adjuvant injection. The TNF-alpha immunoreactivity was most prominent in
      the leptomeninges covering astrocytes. On the other hand, the IL-10
      immunoreactivity was observed in both activated microglia and astrocytes
      localized along the leptomeninges. Cultured leptomeningeal cells covering the
      cerebral cortex released TNF-alpha which was significantly increased by
      lipopolysaccharide (LPS). Upon stimulation with LPS, cultured leptomeningeal
      cells also secreted interleukin-1beta and interleukin-6 with differential time
      courses. When primary cultured rat astrocytes and microglia were treated with the
      conditioned medium of LPS-activated cultured leptomeningeal cells, the
      immunoreactivity of IL-10 was markedly increased. These observations strongly
      suggest that leptomeningeal cells release pro-inflammatory cytokines to activate
      both microglia and astrocytes during systemic inflammation. The activated
      astrocytes and microglia may in turn regulate anti-inflammatory response in the
      brain by providing IL-10.

PMID- 16095727
TI  - Use of electric cell-substrate impedance sensing as a tool for quantifying
      cytopathic effect in influenza A virus infected MDCK cells in real-time.
AB  - Resulting from its subjective nature, cytopathic effect (CPE) due to virus
      infection in cell culture has long been difficult to quantify. This report
      illustrates the use of electric cell-substrate impedance sensing (ECIS) for
      monitoring the progression of CPE due to influenza A virus infection. ECIS
      monitors the impedance of a non-invasive ac current flowing through cell culture
      medium by gold film electrodes placed on the surface of the culture dish. As
      cultured cells attach and spread onto the electrodes, the current is impeded
      proportional to the number of attached cells, the number of tight junctions
      between cells and the shortness in distance between the cells and the substratum.
      In the case at hand, a healthy monolayer of cells was insulted with influenza A
      virus infection and exhibited a characteristic rounded cell morphology and cell
      detachment. These effects resulted in reduced impedance, which was monitored with
      ECIS. Since data obtained through ECIS are both quantitative and in real-time, it
      was possible to monitor continuously cell behavior during infection. This, in
      turn, allowed for a more detailed and comprehensive data set to analyze. More
      importantly, through ammonium chloride treatment of cells, it was also shown that
      ECIS may be exploited to examine a treatment's effect on the reduction of
      resistance because of its antiviral activity. Thus, ECIS may be a powerful
      approach for screening antiviral compounds quantitatively in a real-time fashion.

PMID- 16095728
TI  - Immunodiagnosis of groundnut and watermelon bud necrosis viruses using polyclonal
      antiserum to recombinant nucleocapsid protein of Groundnut bud necrosis virus.
AB  - In vitro gene expression strategy was used for the production of polyclonal
      antiserum to the nucleocapsid protein (NP) of Groundnut bud necrosis virus
      (GBNV). The GBNV NP gene from cowpea isolate was cloned into 6x His-tagged UA
      cloning vector and expressed in Escherichia coli [M15] cells. The fusion protein
      was detected in insoluble fraction and was purified by using Ni-NTA agarose
      resin. The purified 6x His-fusion protein ( approximately 32 kDa) was used for
      immunisation to produce a high titre polyclonal antiserum. The antiserum to the
      NP of GBNV at 1:4000 dilution detected successfully natural infection of GBNV and
      Watermelon bud necrosis virus in a wide range of cucurbitaceous, leguminous and
      solanaceous hosts from different locations.

PMID- 16095729
TI  - Immediate early gene expression following exposure to acoustic and visual
      components of courtship in zebra finches.
AB  - Sensory driven immediate early gene expression (IEG) has been a key tool to
      explore auditory perceptual areas in the avian brain. Most work on IEG expression
      in songbirds such as zebra finches has focused on playback of acoustic stimuli
      and its effect on auditory processing areas such as caudal medial mesopallium
      (CMM) caudal medial nidopallium (NCM). However, in a natural setting, the
      courtship displays of songbirds (including zebra finches) include visual as well
      as acoustic components. To determine whether the visual stimulus of a courting
      male modifies song-induced expression of the IEG ZENK in the auditory forebrain
      we exposed male and female zebra finches to acoustic (song) and visual (dancing)
      components of courtship. Birds were played digital movies with either combined
      audio and video, audio only, video only, or neither audio nor video (control). We
      found significantly increased levels of Zenk response in the auditory region CMM
      in the two treatment groups exposed to acoustic stimuli compared to the control
      group. The video only group had an intermediate response, suggesting potential
      effect of visual input on activity in these auditory brain regions. Finally, we
      unexpectedly found a lateralization of Zenk response that was independent of sex,
      brain region, or treatment condition, such that Zenk immunoreactivity was
      consistently higher in the left hemisphere than in the right and the majority of
      individual birds were left-hemisphere dominant.

PMID- 16095730
TI  - Behavioral characteristics of rats predisposed to learned helplessness: reduced
      reward sensitivity, increased novelty seeking, and persistent fear memories.
AB  - The congenitally helpless rat strain, which was selectively bred for increased
      susceptibility to learned helplessness, may model the predisposition to affective
      disorders, including depression and post-traumatic stress disorder. Other than
      the selected trait, the behavior of this strain is not well characterized. In
      this study, we assessed congenitally helpless rats on several behavioral tests.
      First, we assessed reward sensitivity by measuring their consumption of a 5%
      sucrose solution. Next, we assessed exploratory behavior and fearfulness in both
      a novel and familiar open field, and in a light-dark test. Finally, we assessed
      fear conditioning by exposing the animals to 4 tone-shock pairs on 1 day
      (acquisition) and then presenting 60 tones over the next 2 days (extinction).
      Compared to normal Sprague-Dawley controls, congenitally helpless rats showed
      less consumption of the sucrose solution and more exploratory behavior in the
      novel, but not the familiar, open fields. They also showed less fearfulness in
      the light-dark test, but more conditioned freezing to the tone predicting shock.
      Moreover, this freezing was resistant to extinction; congenitally helpless rats
      not only failed to show a fear decrement during extinction, but actually showed
      increased fear, a phenomenon termed "paradoxical enhancement." Thus, congenitally
      helpless rats appear to have a behavioral phenotype characterized by reduced
      sensitivity to reward, increased drive to explore novel environments, and
      increased propensity to form and maintain fear-associated memories. This
      behavioral phenotype is discussed as resembling the personality of humans
      vulnerable to post-traumatic stress disorder.

PMID- 16095731
TI  - Increased anxiety-like behaviors and mitochondrial dysfunction in mice with
      targeted mutation of the Bcl-2 gene: further support for the involvement of
      mitochondrial function in anxiety disorders.
AB  - There is growing evidence that anxiety disorders are associated with impairments
      of cellular plasticity and resilience. Paralleling these advances in our
      understanding of the neurobiologic underpinnings of anxiety disorders is the
      growing appreciation of the diverse functions that mitochondria play in
      regulating integrated CNS function. The emerging data suggest that mitochondrial
      Ca2+ sequestration has a key role in modulating the tone of synaptic plasticity
      in a variety of neuroanatomical regions, including those implicated in the
      pathophysiology of anxiety disorders. Furthermore, activation of peripheral
      mitochondrial benzodiazepine receptors resulted in reduced anxiety in rats. One
      of the major modulators of mitochondrial function is Bcl-2 proteins imbedded in
      the inner mitochondrial membrane. Bcl-2 overexpression increases mitochondria
      Ca2+ uptake capacity and resistance to Ca2+-inhibition of respiration and
      upregulation of Bcl-2 increases maximal uptake capacity of mitochondria. We have,
      therefore, explored the significance of Bcl-2 in the association between
      mitochondrial function and affective disorders testing Bcl-2 heterozygote mice in
      models of affective and anxiety disorders. Mutant mice have reduced mitochondrial
      Bcl-2 levels, and although they have no gross behavioral abnormalities, they
      demonstrate a significant increase of anxiety-like behaviors. Bcl-2 heterozygote
      mice spent less time in the center of an open field, spent less time outside an
      enclosure in the "emergence test", were less likely to explore the transparent
      part of a black/white box or the open arms of an elevated plus maze compared with
      WT controls. Mutant mice did not differ from WT in measures of locomotion or in
      the forced swim test for depression-like behavior suggesting a specific effect on
      anxiety-like behaviors. Our study, therefore demonstrates that Bcl-2 may be a key
      factor in anxiety disorders and that its effects may possibly originate from its
      role in the mitochondria.

PMID- 16095732
TI  - Time-course of changes in levels of interleukin 6 in acutely decompensated heart
      failure.

PMID- 16095733
TI  - Selective inhibition of pinacidil effects by estrogen in guinea pig heart.
AB  - BACKGROUND: Recently, gender related differences in heart function have been
      extensively studied. Some of them, as differences in repolarization between males
      and females have been explained by direct effect of estrogen on delayed rectifier
      K+ channels and Ca2+ channels. It seems that estrogen induces overexpression of
      SUR2A subunits of ATP-sensitive K+ channels. The aim of this paper was to compare
      heart rate changes in male and female guinea pigs in the presence of different
      potassium channel openers (PCOs). METHODS: We used spontaneously beating right
      atria from control and estrogen receptor modulator-treated male and female guinea
      pigs (17-beta-estradiol as a stimulator and tamoxifen as a blocker of estrogen
      receptor located in heart muscle). RESULTS: In control females, rilmakalim and
      diazoxide, but not pinacidil elicited concentration-dependent decrease of heart
      rate. On the other hand, all three PCOs induced similar negative chronotropic
      action in hearts obtained from male control group (Emax was between -40 and -70
      bpm, respectively). After two weeks of treatment with 17-beta-estradiol,
      pinacidil failed to significantly decrease heart rate in males however, tamoxifen
      pretreated female group responded by decrease in automatism in the presence of
      rising concentration of pinacidil (Emax=-45+/-6 bpm, not significantly different
      from Emax in male control=-40+/-5 bpm, n=7). Interestingly, we observed lower
      blood concentration of the heart form of lactate dehydrogenase (H-LDH) in female
      than in male control group. Moreover, H-LDH concentration increased in tamoxifen
      pretreated female group and decreased in 17-beta-estradiol-treated male group.
      CONCLUSION: Our results indicate that estrogen downregulates H-LDH production and
      specifically modulate pinacidil action in guinea pig right atria, probably by
      changes of binding site for this drug in SUR2A receptor, but not for rilmakalim
      and diazoxide.

PMID- 16095734
TI  - Cardiac resynchronization therapy in congenital heart disease.
AB  - While cardiac resynchronization therapy (CRT) is of proven benefit in selected
      patients with severe ischemic or dilated cardiomyopathy, refractory symptoms, and
      conduction delay, extrapolation to congenital heart disease is not
      straightforward. This rapidly expanding patient population commonly suffers from
      heart failure, particularly in the presence of a single or systemic right
      ventricle. Surgical repair may also contribute to ventricular asynchrony. In this
      systematic review, the current state of knowledge regarding CRT in congenital
      heart disease is presented. Issues specific to congenital heart disease including
      right bundle branch block, right (pulmonary) ventricular dysfunction, systemic
      right ventricular dysfunction, and single ventricle dysfunction are explored.
      Evidence-based CRT applications for each of these particular conditions are
      reviewed. Initial experience with CRT in the acute postoperative setting and
      longer-term, including our own, is elaborated. Unlike standard indications based
      on multiple randomized clinical trials, supporting evidence for CRT in congenital
      heart disease is limited to case reports, case series, and small experimental
      crossover studies in the acute postoperative setting. The heterogeneous patient
      population, technical limitations from patient size, vascular access issues, and
      unique forms of ventricular asynchrony further obscure the selection of potential
      beneficiaries. Despite these limitations, experience thus far has been favorable.
      Quality of current data precludes definitive evidence-based recommendations, but
      optimistic initial results suggest that research endeavors in this field should
      be pursued. Multicenter prospective collaborative efforts are to be encouraged.

PMID- 16095736
TI  - Comparison of real-time PCR and pyrosequencing for typing Bordetella pertussis
      toxin subunit 1 variants.
AB  - We describe two newly developed methods for rapid typing of the pertussis toxin
      subunit 1 gene (ptxS1). A real-time PCR assay based on hybridization probes and a
      Pyrosequencing assay were developed and the specificity, sensitivity, cost, hands
      on time and post-assay data processing were compared to Sanger sequencing. Both
      methods enabled discrimination of all four allelic variants, correctly identified
      all ptxS1 alleles of 143 strains tested and proved suitable for large-scale
      screening of B. pertussis strains.

PMID- 16095737
TI  - Correlation of 3D-planned and measured dosimetry of photon and electron
      craniospinal radiation in a pediatric anthropomorphic phantom.
AB  - BACKGROUND AND PURPOSE: Improved radiotherapy techniques in pediatric
      craniospinal therapy (CSRT) strive to reduce risks of late morbidity. Using a
      pediatric anthropomorphic phantom, this research correlated measured target and
      normal tissue dose to that predicted from a 3D planning system (3D-RTP). PATIENTS
      AND METHODS: A pediatric anthropomorphic phantom was planned following French
      Society of Pediatric Oncology (SFOP) protocols. Thermoluminescent detectors
      (TLDs) were used to perform dosimetric measurements during treatment. 4 and 6MV
      photon fields with multi leaf collimation (MLC) or custom blocks were compared to
      3D-RTP computer (ADAC Pinnacle) predictions for cranial fields. Spinal dosimetry
      was studied using photons (4 and 6MV) and electrons (9 and 12MeV). RESULTS: 3D
      RTP predictions generally concurred with dose received in cranial and spinal
      sites. The measured dose was over-predicted significantly by the 3D-RTP in the
      anterior cranial fossa. Normal tissue doses were reduced when treating the spine
      using megavoltage electron beams instead of photons. CONCLUSIONS: Treating the
      spinal field with electrons minimises the risk of pulmonary sequelae, however
      electron energy selection is critical to achieve adequate spinal field coverage.
      Despite adhering to a major trial protocol guideline, dose at the floor of the
      anterior cranial fossa remains a potential clinical problem and 3D-RTP do not
      predict this well.

PMID- 16095738
TI  - Role of the inertial eigenvectors in proprioception near the limits of arm
      adduction range of motion.
AB  - Common everyday activities such as reaching for a cup, combing one's hair, or
      positioning a tool involve the accurate registration of the limb's orientation
      relative to the body and the environment. Past work has demonstrated that the
      ability of humans to perceive the spatial orientation of an occluded arm is tied
      to the arm's inertial eigenvectors, invariant mechanical parameters corresponding
      to a limb's axes of rotational symmetry. In a recent study participants pointed
      to visible targets while the arms' inertial eigenvectors were displaced by
      asymmetrically weighted splints. The lack of an effect of those splints on
      pointing error led them to conclude that inertial eigenvectors are not the
      primary invariants used for proprioception. However, their data suggested an
      effect of the eigenvectors, but only for conditions in which pointing did not
      require placing the arm near the limits of shoulder adduction range of motion. In
      the present study we found a significant effect of displacing the eigenvector for
      all tested arm angles, regardless of degree of shoulder adduction. Overall, the
      results supported the hypothesis that proprioception is based on sensitivity to
      the limb's inertial eigenvectors, with no reduction of the eigenvector effect
      when adducting the arm so as to reach far across the body midline.

PMID- 16095739
TI  - Perceptual-cognitive expertise in sport: some considerations when applying the
      expert performance approach.
AB  - The number of researchers studying perceptual-cognitive expertise in sport is
      increasing. The intention in this paper is to review the currently accepted
      framework for studying expert performance and to consider implications for
      undertaking research work in the area of perceptual-cognitive expertise in sport.
      The expert performance approach presents a descriptive and inductive approach for
      the systematic study of expert performance. The nature of expert performance is
      initially captured in the laboratory using representative tasks that identify
      reliably superior performance. Process-tracing measures are employed to determine
      the mechanisms that mediate expert performance on the task. Finally, the specific
      types of activities that lead to the acquisition and development of these
      mediating mechanisms are identified. General principles and mechanisms may be
      discovered and then validated by more traditional experimental designs. The
      relevance of this approach to the study of perceptual-cognitive expertise in
      sport is discussed and suggestions for future work highlighted.

PMID- 16095740
TI  - Clinico-pathological rescue of a model mouse of Huntington's disease by siRNA.
AB  - Huntington's disease (HD) is an autosomal dominant inheritable neurodegenerative
      disorder currently without effective treatment. It is caused by an expanded
      polyglutamine (poly Q) tract in the corresponding protein, huntingtin (htt), and
      therefore suppressing the huntingtin expression in brain neurons is expected to
      delay the onset and mitigate the severity of the disease. Here, we have used
      small interfering RNAs (siRNAs) directed against the huntingtin gene to repress
      the transgenic mutant huntingtin expression in an HD mouse model, R6/2. Results
      showed that intraventricular injection of siRNAs at an early postnatal period
      inhibited transgenic huntingtin expression in brain neurons and induced a
      decrease in the numbers and sizes of intranuclear inclusions in striatal neurons.
      Treatments using this siRNA significantly prolonged model mice longevity,
      improved motor function and slowed down the loss of body weight. This work
      suggests that siRNA-based therapy is promising as a future treatment for HD.

PMID- 16095741
TI  - Sol-gel encapsulation: an efficient and versatile immobilization technique for
      cutinase in non-aqueous media.
AB  - Cutinase from Fusarium solani pisi was encapsulated in sol-gel matrices prepared
      with a combination of alkyl-alkoxysilane precursors of different chain-lengths.
      The specific activity of cutinase in a model transesterification reaction at
      fixed water activity in n-hexane was highest for the precursor combination
      tetramethoxysilane/n-butyltrimetoxysilane (TMOS/BTMS) in a 1:5 ratio, lower and
      higher chain lengths of the mono-alkylated precursor or decreasing proportions of
      the latter relative to TMOS leading to lower enzyme activity. Results obtained
      using combinations of three precursors confirmed the beneficial effect of the
      presence of BTMS in the preparations. Scanning electron microscopy of the 1:5
      TMOS/n-alkylTMS gels showed a direct correlation between the macropore dimensions
      and the alkyl chain length of the alkylated precursor and revealed that TMOS/n
      octylTMS gels suffered extensive pore collapse during the drying process. The
      specific activity of TMOS/BTMS sol-gel entrapped cutinase was similar to that
      exhibited by the enzyme immobilized by adsorption on zeolite NaY. However, the
      incorporation of different additives (zeolites, silica, Biogel, grinded sol-gel,
      etc.) having in common the capability to react with residual silanol groups of
      the sol-gel matrix brought about remarkable enhancements of cutinase activity,
      despite the fact that the global porosity of the gels did not change. The
      behavior of the gels in supercritical CO 2 (sc-CO 2) paralleled that exhibited in
      n-hexane, although cutinase activity was ca. one order of magnitude lower (i.e.
      sol-gel encapsulation did not prevent the deleterious effect of CO 2. The impact
      that functionalization of some of the additives had on cutinase activity
      indicates that the enzyme/matrix interactions must play an important role. Some
      of the best additives from the standpoint of enzyme activity were also the best
      from the standpoint of its operational stability (ca. 80% retention of enzyme
      activity at the tenth reutilization cycle). None of the additives that proved
      effective for cutinase could improve the catalytic activity of sol-gel
      encapsulated Pseudomonas cepacia lipase.

PMID- 16095742
TI  - Introduction of DNA into Actinomycetes by bacterial conjugation from E. coli--an
      evaluation of various transfer systems.
AB  - Gene transfer is a basic requirement for optimizing bioactive natural substances
      produced by an increasing number of industrially used microorganisms. We have
      analyzed quantitatively horizontal gene transfer from Escherichia coli to
      Actinomycetes. The efficiencies of DNA transfer of four different systems were
      compared that consist of conjugative and mobilizable plasmids with a broad-host
      range. Three novel binary vector set-ups were constructed based on: (i) the IncQ
      group of mobilizable plasmids (RSF1010), (ii) IncQ-like pTF-FC2 and (iii) pSB102
      that belongs to a new class of broad-host-range plasmids. The established system
      based on the IncPalpha group of conjugative plasmids served as the reference. For
      all plasmids constructed, we confirmed the functional integrity of the selected
      transfer machineries by intrageneric matings between E. coli strains. We
      demonstrate that the transfer systems introduced in this study are efficient in
      mediating gene transfer from E. coli to Actinomycetes and are possible
      alternatives for gene transfer into Actinomycetes for which the IncPalpha-based
      transfer system is not applicable. The use of plasmids that integrate into the
      recipients' chromosomes compared to that of plasmids replicating autonomously is
      shown to allow the access to a wider range of hosts.

PMID- 16095744
TI  - Rapid isolation of high quality, multimeric plasmid DNA using zwitterionic
      detergent.
AB  - Purification of plasmid DNA from bacteria is an essential tool in recombinant DNA
      technology and has become an essential task in laboratories to industries.
      Moreover, the recent progress of "Gene therapy" and "Genetic vaccination" also
      demands production of pharmaceutical grade plasmid DNA in 'kilogram' level.
      Despite existence of a number of purification protocols, all most all have been
      originated from a pioneering work [Birnboim, H.C., Doly, J., 1979. A rapid
      extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 7,
      1513-1523] and so suffer from one or more drawbacks, such as purification time,
      purity or quantity of isolated plasmid DNA. Here, we have reported an innovative
      approach for isolation of highly pure and functional plasmid DNA in significant
      amount, based on generation of "soft protein aggregate" with the help of
      zwitterionic detergents and alkali. Solibilized proteins and RNA could be removed
      by a simple and mild washing with Tris buffer of low ionic strength and
      multimeric plasmid DNA could be eluted in a single step from the protein
      aggregate. Additionally, isolated plasmid DNA could easily be digested by
      restriction enzymes and had high functionality in protein expression. Thus,
      considering both its remarkable simplicity and efficiency in producing
      sufficiently pure plasmid DNA, the new strategy would emerge a useful tool in
      modern recombinant technology and therapeutic applications.

PMID- 16095743
TI  - Choice of the adequate detection time for the accurate evaluation of the
      efficiency of siRNA-induced gene silencing.
AB  - RNA interference (RNAi) mediated by small interfering RNA (siRNA) has become a
      popular tool of examining the function of various genes. However, many studies
      have failed to identify any inhibitory effect of the siRNAs on the expression of
      the target gene, even though the siRNA being tested had been designed sequence
      specifically. In order to determine if this failure is due to the incorrect
      choice of observation time rather than that of the target site of the gene of
      interest, this study examined the RNAi efficiency of a vector-driven siRNA
      targeting two different reporter proteins, EGFP and d2EGFP, whose targeted
      sequences were identical but the half-lives within the cells differed remarkably
      from each other (>24h versus 2h), during the time course after transfection. The
      EGFP expression levels in both cells were reduced in time-dependent manner but
      the reduction patterns were quite different from each other. The RNAi efficiency
      varied among the different observation time points and the time required for the
      maximum RNAi efficiency was proportional to the half-life of the target protein.
      Stable knocked down cell lines for EGFP expression were then established and the
      reduced EGFP expression levels in these cell lines were retained for a long
      period. These results suggest that the choice of an adequate observation time or
      the establishment of stable knocked down cells by antibiotic selection might be
      required for making an accurate evaluation of the RNAi effect on the target
      protein possessing a long half-life.

PMID- 16095745
TI  - Application of bioreactor system for large-scale production of Eleutherococcus
      sessiliflorus somatic embryos in an air-lift bioreactor and production of
      eleutherosides.
AB  - Embryogenic callus was induced from leaf explants of Eleutherococcus
      sessiliflorus cultured on Murashige and Skoog (MS) basal medium supplemented with
      1 mg l(-1) 2,4-dichlorophenoxyacetic acid (2,4-D), while no plant growth
      regulators were needed for embryo maturation. The addition of 1 mg l(-1) 2,4-D
      was needed to maintain the embryogenic culture by preventing embryo maturation.
      Optimal embryo germination and plantlet development was achieved on MS medium
      with 4 mg l(-1) gibberellic acid (GA(3)). Low-strength MS medium (1/2 and 1/3
      strength) was more effective than full-strength MS for the production of normal
      plantlets with well-developed shoots and roots. The plants were successfully
      transferred to soil. Embryogenic callus was used to establish a suspension
      culture for subsequent production of somatic embryos in bioreactor. By
      inoculating 10 g of embryogenic cells (fresh weight) into a 3l balloon type
      bubble bioreactor (BTBB) containing 2l MS medium without plant growth regulators,
      121.8 g mature somatic embryos at different developmental stages were harvested
      and could be separated by filtration. Cotyledonary somatic embryos were
      germinated, and these converted into plantlets following transfer to a 3l BTBB
      containing 2l MS medium with 4 mg l(-1) GA3. HPLC analysis revealed that the
      total eleutherosides were significantly higher in leaves of field grown plants as
      compared to different stages of somatic embryo. However, the content of
      eleutheroside B was highest in germinated embryos. Germinated embryos also had
      higher contents of eleutheroside E and eleutheroside E1 as compared to other
      developmental stages. This result indicates that an efficient protocol for the
      mass production of E. sessiliflorus biomass can be achieved by bioreactor culture
      of somatic embryos and can be used as a source of medicinal raw materials.

PMID- 16095746
TI  - The 2b protein as a minor structural component of PRRSV.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) ORF2 contains an
      internal ORF that codes for a small non-glycosylated protein known as 2b.
      Previous work had identified the presence of a 10kDa 2b protein in virus-infected
      cells and the induction of an anti-2b response in PRRSV-infected pigs, as well as
      a possible association of 2b with the virion (, Virology 287:183-191). In this
      study, we utilized two experimental approaches, including the use of a 2b peptide
      specific monoclonal antibody, to demonstrate that the PRRSV 2b protein is an
      integral component of the PRRSV virion. This study suggests that 2b in PRRSV is
      similar to the E protein in EAV and forms a minor structural component of the
      virion.

PMID- 16095747
TI  - Synthesis of a biodegradable tadpole-shaped polymer via the coupling reaction of
      polylactide onto mono(6-(2-aminoethyl)amino-6-deoxy)-beta-cyclodextrin and its
      properties as the new carrier of protein delivery system.
AB  - A new tadpole-shaped polymer was synthesized via the coupling reaction of poly(DL
      lactide) (PLA) onto mono(6-(2-aminoethyl)amino-6-deoxy)-beta-cyclodextrin (CDen)
      using N,N'-Dicyclohexycarbodiimide as the catalyst. The structures of CDenPLA as
      the products were characterized with infrared spectrometry, nuclear magnetic
      resonance and their molecular weights were determined by gel permeation
      chromatography. The tadpole-shaped polymer possessed both a hydrophilic head that
      could bind some residues on a protein and a hydrophobic polylactide tail so that
      it could be amphiphilic. Two methods, double emulsion (DE) and nanoprecipitation
      (NP), were employed to fabricate the polymeric nanoparticles into which the
      bovine serum albumin was loaded as a model protein. The nanoparticles with a
      hydrophobic core of the PLA segments covered with the hydrophilic corona layer of
      the cyclodextrin moiety could be formed from the copolymers using NP method as
      identified by 1HNMR. Influence of the preparation conditions on the nanoparticles
      size, encapsulation efficiency and release profile in vitro was investigated. The
      encapsulation efficiency of the BSA-loaded nanoparticles with the average
      diameter of 377 nm was 71.6% under an optimized condition. The structure
      maintenance in the nanoparticle preparation and release in vitro was also
      measured via sodium dodecyl sulfate polyacrylamide gel electrophoresis and
      circular dichroism spectrometry. The results showed that the new copolymer could
      load BSA effectively and BSA kept stable after it was released from the
      nanoparticles.

PMID- 16095748
TI  - Calcium silicate based microspheres of repaglinide for gastroretentive floating
      drug delivery: preparation and in vitro characterization.
AB  - Gastroretentive dosage forms have potential for use as controlled-release drug
      delivery systems. Multiple unit systems avoid the 'all-or-none' gastric emptying
      nature of single-unit systems. A controlled release system designed to increase
      its residence time in the stomach without contact with the mucosa was achieved
      through the preparation of floating microspheres by the emulsion solvent
      diffusion technique consisting of (i) calcium silicate (FLR) as porous carrier;
      (ii) repaglinide, an oral hypoglycemic agent; and (iii) Eudragit S as polymer.
      The effect of various formulation and process variables on the internal and
      external particle morphology, micromeritic properties, in vitro floating
      behavior, physical state of the incorporated drug, drug loading and in vitro drug
      release were studied. The microparticles were found to be regular in shape and
      highly porous. The release rate was determined in simulated gastro-intestinal
      fluids at 37 degrees C. The formulation demonstrated favorable in vitro floating
      and release characteristics. The drug encapsulation efficiency was high.
      Incorporation of FLR in the microspheres proved to be an effective method to
      achieve the desired release behavior and buoyancy. The designed system, combining
      excellent buoyant ability and suitable drug release pattern, could possibly be
      advantageous in terms of increased bioavailability of repaglinide.

PMID- 16095749
TI  - Self-medication with antibiotics--does it really happen in Europe?
AB  - AIMS AND METHODS: The aim of this study was to determine whether antibiotics are
      used for self-medication in southern Spain, a region belonging to European Union.
      The data were collected by a survey in the Costa del Sol region, Spain during
      2002 by using a convenience sample of 1000 Finns living permanently in the area
      (response rate 53%, n=530). RESULTS: Antibiotics were used by 28% of the
      respondents during the previous 6 months before the query. Of the antibiotic
      users, 41% had bought their antibiotics without a prescription. Clearly the most
      common indication for antibiotic use was common cold, with almost half (45%) of
      the antibiotic users reporting it as purpose of medication, followed by sore
      throat (17%). The number of courses did not differ between prescription and non
      prescription antibiotic users, most (64%) of the users having used one course.
      Neither did the groups differ according to background variables used, including
      the frequency of experiencing adverse reactions. CONCLUSIONS: Unnecessary and
      unrational self-medication with antibiotics seems to be common in southern Spain
      among Finnish immigrants. This may indicate that Spanish health care system,
      including community pharmacies are failing their task in enhancing rational use
      of medicines. It is important that all the member countries within EU will take
      their responsibility in promoting public health goals in their national policy,
      e.g., in minimising the antibiotic resistance for expanding.

PMID- 16095750
TI  - The promiscuous primase.
AB  - DNA primases are essential for the initiation of DNA replication and progression
      of the replication fork. Recent phylogenetic analyses coupled with biochemical
      and structural studies have revealed that the arrangement of catalytic residues
      within the archaeal and eukaryotic primase has significant similarity to those of
      the Pol X family of DNA-repair polymerases. Furthermore, two additional groups of
      enzymes, the ligase/primase of the bacterial nonhomologous end-joining machinery
      and a putative replicase from an archaeal plasmid have shown striking functional
      and structural similarities to the core primase. The promiscuous nature of the
      archaeal primases suggests that these proteins might have additional roles in DNA
      repair in the archaea.

PMID- 16095751
TI  - Extravasation of plasma proteins can confound interpretation of proteomic studies
      of brain: a lesson from apo A-I in mesial temporal lobe epilepsy.
AB  - Apolipoprotein A-I (apo A-I), a major component of high density lipoproteins, has
      been shown to be involved in lipid metabolism, cholesterol homeostasis and
      degeneration/regeneration of brain tissues and was proposed as a useful marker
      for the extent and severity of CNS injury. We searched for aberrant protein
      expression in hippocampus from patients with mesial temporal lobe epilepsy (MTLE)
      by an analytical method based on two-dimensional gel electrophoresis coupled with
      mass spectrometry (MALDI-TOF/TOF) and unambiguously identified 2 spots as
      apolipoprotein A-I forms in brain of MTLE patients with 7.5-fold increased levels
      (controls: 0.046 +/- 0.046; MTLE patients: 0.343 +/- 0.154, mean +/- SD, P =
      0.003). Western blot analysis confirmed increased apo A-I levels in MTLE.
      Immunohistochemistry detected staining for apo A-I extracellularly in perivasal
      brain parenchyma, neuropil and areas with increased glial fibrillary acidic
      protein (GFAP) expression as well as some pyramidal neurons and subpial
      astrocytes. These findings indicate that the increase of apo A-I in MTLE was
      possibly not reflecting a pathogenetic role but was rather due to extravasates,
      bleedings or increase of microvascular endothelial cells known to synthesize apo
      A-I. Care has to be taken when protein expressional findings are to be
      interpreted in the presence of plasma proteins, including apo A-I, thus clearly
      representing a confounding factor.

PMID- 16095752
TI  - NAPOR-3 RNA binding protein is required for apoptosis in hippocampus.
AB  - NAPOR-3 is a central nervous system RNA binding protein that is associated with
      downstream mRNA targets and has been demonstrated to be selectively overexpressed
      during apoptotic cell death. In this study, we first examined the regional
      distribution of NAPOR-3 mRNA in the adult rat brain by in situ hybridization: the
      transcript was abundantly expressed in many brain regions, mostly in gray matter,
      including the CA1-CA4 regions and dentate gyrus of the hippocampus, the piriform
      cortex and the cerebellar granule cell layer. We then investigated the role of
      NAPOR-3 in neuronal cell death by monitoring its mRNA and protein expression
      levels using semiquantitative RT-PCR and Western blotting, respectively. NAPOR-3
      was overexpressed in rat organotypic slices exposed to staurosporine and to
      oxygen-glucose deprivation (OGD), an in vitro model of apoptotic cerebral
      ischemia, but not when exposed to glutamate toxicity. Our results also
      demonstrate that NAPOR-3 gene overexpression is an early step in the chain of
      signaling events leading to apoptosis, taking place upstream of caspase-3
      activation. Finally, antisense-mediated downregulation of NAPOR-3 gene expression
      protected hippocampal cultures against OGD-induced apoptosis and prevented
      caspase-3 activation. Our results demonstrate that NAPOR-3 gene overexpression is
      necessary for the execution of OGD-induced programmed cell death.

PMID- 16095753
TI  - Contamination potential of nitrogen compounds in the heterogeneous aquifers of
      the Choushui River alluvial fan, Taiwan.
AB  - This study aimed to analyze the contamination potential associated with the
      reactive transport of nitrate-N and ammonium-N in the Choushui River alluvial
      fan, Taiwan and to evaluate a risk region in developing a groundwater protection
      policy in 2021. In this area, an aquifer redox sequence provided a good
      understanding of the spatial distributions of nitrate-N and ammonium-N and of
      aerobic and anaerobic environments. Equiprobable hydraulic conductivity (K)
      fields reproduced by geostatistical methods characterized the spatial uncertainty
      of contaminant transport in the heterogeneous aquifer. Nitrogen contamination
      potential fronts for high and low threshold concentrations based on a 95% risk
      probability were used to assess different levels of risk. The simulated result
      reveals that the spatial uncertainty of highly heterogeneous K fields governs the
      contamination potential assessment of the nitrogen compounds along the regional
      flow directions. The contamination potential of nitrate-N is more uncertain than
      that for ammonium-N. The high nitrate-N concentrations (> or =3 mg/L) are
      prevalent in the aerobic environment. The low concentration nitrate-N plumes (0.5
      3 mg/L) gradually migrate to the mid-fan area and to a maximum distance of 15 km
      from the aerobic region. The nitrate-N plumes pose a potential human health risk
      in the aerobic and anaerobic environments. The ammonium-N plumes remain stably
      confined to the distal-fan and partial mid-fan areas.

PMID- 16095754
TI  - A risk index for characterising flow pattern in soils using dye tracer
      distributions.
AB  - A novel risk index for the vulnerability of groundwater by pollutants is defined
      as the form parameter of the Pareto distribution and estimated from dye tracer
      experiments. The Pareto distribution appears as the limit distribution of the
      extreme value theory, which has been applied to an idealized model of drops that
      run along a path. The properties of the risk index are investigated by a Monte
      Carlo study, where the paths are modelled by means of Gaussian random fields. The
      method is applied to three profiles obtained from Brilliant Blue tracer
      experiments of the soil physics group at ETH Zurich. It is shown that a single
      profile can be rather well characterised by the risk index. However, due to the
      high variability of the dye tracer profiles, an estimated number of at least 15
      profile pictures are necessary to characterise a soil.

PMID- 16095755
TI  - Regional sampling and the effects of experimental heart failure in sheep:
      differential responses in A, B and C-type natriuretic peptides.
AB  - While regional plasma concentrations of the endocrine hormones atrial and brain
      natriuretic peptide (ANP and BNP) have been studied, there are few reports of
      regional changes in the largely paracrine C-type natriuretic peptide (CNP) and
      its amino terminal fragment NT-CNP. Accordingly, we have performed trans-organ
      arteriovenous sampling for measurement of plasma ANP, BNP, CNP and NT-CNP in
      anesthetized sheep before and after induction of experimental heart failure. ANP
      and BNP plasma concentrations are sourced from a single organ (the heart) and are
      subject to substantial extraction across most tissue beds. In contrast, our data
      demonstrate that multiple tissues including liver, heart, hind limb and kidney
      contribute to circulating CNP. Given that arteriovenous gradients for NT-CNP were
      similar, this is likely to represent de novo secretion. Circulating levels of CNP
      and NT-CNP were raised in heart failure but to a much lesser degree than ANP and
      BNP. There was no evidence of net extraction of CNP or NT-CNP across any tissue
      bed.

PMID- 16095756
TI  - Expression of urocortin 3/stresscopin in human adrenal glands and adrenal tumors.
AB  - Urocortin 3 (Ucn 3)/stresscopin (SCP) is a novel peptide of the corticotropin
      releasing factor (CRF) family and is a specific ligand for the CRF type 2
      receptor. In the present study, we studied expression of Ucn3/SCP in the normal
      adrenal and adrenal tumors by radioimmunoassay and reverse transcriptase
      polymerase chain reaction (RT-PCR). High concentrations of immunoreactive (IR)
      Ucn3 were present in the normal portions of adrenal glands (4.2+/-0.51 pmol/g wet
      weight, mean+/-S.E.M., n = 14), and the levels were higher than those in the
      brain. IR-Ucn3 was also detected in the tumor tissues of aldosterone-secreting
      adenomas (6.2+/-0.6 pmol/g wet weight, n = 10), cortisol-secreting adenomas
      (5.0+/-1.2 pmol/g wet weight, n = 4), and pheochromocytomas (1.9+/-0.4 pmol/g wet
      weight, n = 7). Reverse phase high performance liquid chromatography showed that
      IR-Ucn3 in normal portions of adrenal glands and aldosterone-secreting adenomas
      was eluted mainly in the positions of Ucn3 and SCP with several minor peaks
      eluting earlier. The RT-PCR showed expression of Ucn3 mRNA in normal portions of
      adrenal gland (positive ratio; 4/4), aldosterone-secreting adenomas (3/4),
      cortisol-secreting adenomas (1/3) and pheochromocytomas (6/7). These findings
      indicate that Ucn3 is produced in normal adrenal and adrenal tumors (both
      adrenocortical tumors and pheochromocytomas), and suggest that Ucn3 acts as an
      autocrine or paracrine regulator in normal adrenal and adrenal tumors.

PMID- 16095757
TI  - Pituitary adenylate cyclase activating polypeptide protects cardiomyocytes
      against oxidative stress-induced apoptosis.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) has well-known
      neuroprotective effects, and one of the main factors leading to neuroprotection
      seems to be its anti-apoptotic effects. The peptide and its receptors are present
      also in the heart, but whether PACAP can be protective in cardiomyocytes, is not
      known. Therefore, the aim of the present study was to investigate the effects of
      PACAP on oxidative stress-induced apoptosis in cardiomyocytes. Our results show
      that PACAP increased cell viability by attenuating H2O2-induced apoptosis in a
      cardiac myocyte culture. PACAP also decreased caspase-3 activity and increased
      the expression of the anti-apoptotic markers Bcl-2 and phospho-Bad. These effects
      of PACAP were counteracted by the PACAP antagonist PACAP6-38. In summary, our
      results show that PACAP is able to attenuate oxidative stress-induced
      cardiomyocyte apoptosis.

PMID- 16095758
TI  - Tricarboxylic acid cycle inhibition by Li+ in the human neuroblastoma SH-SY5Y
      cell line: a 13C NMR isotopomer analysis.
AB  - Li+ effects on glucose metabolism and on the competitive metabolism of glucose
      and lactate were investigated in the human neuroblastoma SH-SY5Y cell line using
      13C NMR spectroscopy. The metabolic model proposed for glucose and lactate
      metabolism in these cells, based on tcaCALC best fitting solutions, for both
      control and Li+ conditions, was consistent with: (i) a single pyruvate pool; (ii)
      anaplerotic flux from endogenous unlabelled substrates; (iii) no cycling between
      pyruvate and oxaloacetate. Li+ was shown to induce a 38 and 53% decrease, for 1
      and 15 mM Li+, respectively, in the rate of glucose conversion into pyruvate,
      when [U-13C]glucose was present, while no effects on lactate production were
      observed. Pyruvate oxidation by the tricarboxylic acid cycle and citrate synthase
      flux were shown to be significantly reduced by 64 and 84% in the presence of 1
      and 15 mM Li+, respectively, suggesting a direct inhibitory effect of Li+ on
      tricarboxylic acid cycle flux. This work also showed that when both glucose and
      lactate are present as energetic substrates, SH-SY5Y cells preferentially
      consumed exogenous lactate over glucose, as 62% of the acetyl-CoA was derived
      from [3-13C]lactate while only 26% was derived from [U-13C]glucose. Li+ did not
      significantly affect the relative utilisation of these two substrates by the
      cells or the residual contribution of unlabelled endogenous sources for the
      acetyl-CoA pool.

PMID- 16095759
TI  - Iron loading inhibits ferroportin1 expression in PC12 cells.
AB  - Ferroportin1 (FP1 or MTP1/IREG1), the product of the SLC40A1 gene, is a main iron
      export protein in mammals. Its mRNA contains an iron response element (IRE) in
      its 5' untranslated region, but the way this gene is regulated by iron is still
      unclear. The existence of FP1 in the brain has been recently confirmed. To better
      understand the role of this important transmembrane iron exporter in brain iron
      homeostasis, we investigated the effects of iron and nitric oxide (NO) on FP1
      expression and that of a FP1 antibody on iron release in nerve growth factor
      treated rat PC12 cells. We found that FP1 expression was down-regulated by iron
      loading but stimulated by iron chelation and treatment with a NO donor, S-nitroso
      N-acetylpenicillamine (SNAP). In addition, a significant decrease in iron release
      was found in cells treated with a FP1 antibody. Our findings imply that
      regulation of FP1 by iron in the cells is at the transcriptional level, rather
      than by an IRE/IRP-mediated pathway. Based on our results and published data, it
      is suggested that the transcriptional and translational (IRP/IRE pathway)
      mechanisms of FP1 expression might both operate in a tissue-specific manner and
      that FP1 might have a role in iron export from PC12 cells.

PMID- 16095760
TI  - Unchanged glutamine synthetase activity and increased NMDA receptor density in
      epileptic human neocortex: implications for the pathophysiology of epilepsy.
AB  - We investigated whether alterations in glutamate metabolising glutamine
      synthetase activity occur in human epileptic neocortex, as shown previously for
      human epileptic hippocampus [Eid, T., Thomas, M.J., Spencer, D.D., Runden-Pran,
      E., Lai, J.C.K., Malthankar, G.V., Kim, J.H., Danbolt, N.C., Ottersen, O.P., de
      Lanerolle, N.C., 2004. Loss of glutamine synthetase in the human epileptic
      hippocampus: possible mechanism for raised extracellular glutamate in mesial
      temporal lobe epilepsy. Lancet 363, 28-37]. Glutamine synthetase activity was
      equivalent in both non-epileptic and epileptic human neocortex. Epileptic tissue,
      however, was characterised by a 37% increase in the density of synaptosomal NMDA
      receptor sites compared to non-epileptic tissue, as revealed by a radioligand
      binding assay (B max(non-epileptic) 1.45 pmol/mg protein and B max(epileptic)
      1.99 pmol/mg protein, P < 0.05). Our findings shed some doubts on a role of
      glutamine synthetase in the pathophysiology of epilepsy in the neocortex.
      However, the detection of a significantly reduced enzymatic activity in the
      epileptic amygdala supports the assumption that the enzyme defect is localized to
      the epileptic mesial temporal lobe of corresponding patients.

PMID- 16095761
TI  - Iminosugars as glycosyltransferase inhibitors: synthesis of
      polyhydroxypyrrolidines and their evaluation on chitin synthase activity.
AB  - Chitin synthase is an enzyme involved in the biosynthesis of chitin, a major
      structural component of the cell wall of many fungi. Since chitin is absent in
      vertebrates, chitin synthase has been envisaged as a valuable target in the
      search for new antifungal agents. In this report, a series of C-2 substituted
      polyhydroxypyrrolidines were designed and synthesized with the aim of mimicking
      the glycosylation involved at the transition state of the enzymatic reaction
      governed by chitin synthase. Some of these models displayed chitin synthase
      inhibition in the millimolar range. However, no significant antifungal activity
      was noted on a panel of fungal strains.

PMID- 16095762
TI  - Structural changes of benzylether derivatives of vesamicol and their influence on
      the binding selectivity to the vesicular acetylcholine transporter.
AB  - 18F labelled vesamicol analogues, which bind to the vesicular acetylcholine
      transporter (VAChT) in central cholinergic nerve terminals, are expected to be
      potential radioligands for the visualisation of cholinergic transmission deficits
      via positron emission tomography (PET). In this report the regioselective
      synthesis of five novel vesamicol analogues as well as their in vitro binding
      properties to the VAChT are described. Beside having the 4-fluorobenzylether
      substitution at the cyclohexyl ring as an unique structural feature, the new
      compounds are additionally modified at the phenyl and piperidine moiety of the
      vesamicol skeleton. The affinity and selectivity to the VAChT were analysed by
      competitive binding studies using tritium labelled radioligands. The VAChT
      affinities (Ki-values) of the novel compounds were estimated ranging between
      7.8+/-3.5 nM and 161.6+/-17.3 nM, thus some of them are binding with higher
      affinity to the transporter than vesamicol. However, the compounds tested
      demonstrated also affinities to the sigma receptors sigma1 and sigma2 ranging
      between 4.1+/-1.5 nM and 327.5+/-75.9 nM. Nevertheless, these data provide the
      basis for future structure-binding-studies and further underline the potential
      and usefulness of vesamicol analogues for imaging of the VAChT.

PMID- 16095763
TI  - Synthesis and in vitro leishmanicidal activity of 2-(1-methyl-5-nitro-1H-imidazol
      2-yl)-5-substituted-1,3,4-thiadiazole derivatives.
AB  - A series of 2-(1-methyl-5-nitroimidazol-2-yl)-5-(1-piperazinyl, 1-piperidinyl and
      1-morpholinyl)-1,3,4-thiadiazoles (3a-g) were synthesized and evaluated for in
      vitro leishmanicidal activity against Leishmania major promastigotes. The
      leishmanicidal data revealed that compounds 3a-g had strong and much better
      leishmanicidal activity than the reference drug pentostam. Compound 3c
      (piperazine analog) was the most active compound (IC50=0.19 microM).

PMID- 16095764
TI  - Design, synthesis and biological activity of acyl substituted 3-amino-5-methyl
      1,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones as potential hypnotic drugs.
AB  - Among the known non-benzodiazepinic hypnotic drugs acting on the alpha1 subunit
      of the GABA-A receptor, Zolpidem, Zaleplon and Indiplon have showed high affinity
      and selectivity. Following a design methodology including pharmacophoric
      requirements and ADME-predicted properties, we have synthesized a library of 3
      amino-4,5-dihydro-1H-pyrazolo[3,4-b]pyridin-6(7H)-ones and their N1-alkyl
      derivatives as new scaffolds for designing non-benzodiazepine BZ receptor
      ligands.

PMID- 16095765
TI  - Antiretroviral therapy affects the composition of weight loss in HIV infection:
      implications for clinical nutrition.
AB  - BACKGROUND: Weight loss is comprised of variable proportions of fat and fat-free
      mass (FFM). HIV-infected patients treated with antiretroviral (ARV) agents may
      lose subcutaneous fat (lipoatrophy) in the absence of FFM depletion, which could
      confound the clinical interpretation of weight loss. METHODS: We retrospectively
      analyzed the results of anthropometric and dual-energy X-ray absorptiometry
      studies in 196 HIV-infected men and women with documented 10% weight loss (HIV
      group), and compared them to 29 untreated, HIV-infected men without 10% weight
      loss (HIV weight-stable), and 109 healthy adults (72 men and 37 women) to
      evaluate the effect of ARV therapy on the composition of weight loss. The HIV
      group was divided into four subgroups according to current ARV therapy: treatment
      naive (59 men and 26 women), nucleoside reverse transcriptase inhibitor (NRTI)
      monotherapy (45 men), dual NRTI therapy (28 men) and highly active ARV therapy
      (HAART) (19 men and 20 women). RESULTS: Ages and heights were similar in all
      groups, while body mass index (BMI) and body composition differed significantly.
      BMI was higher in HIV-infected men and women on HAART than in the other HIV
      groups, although less than in HIV weight-stable (P=0.36) and healthy controls
      (P<0.0005). Fat content was lower in all HIV groups than in controls (P<0.001),
      while FFM was similar in HIV-infected men and women on dual NRTI and HAART and in
      controls. Comparison with HIV weight-stable gave higher estimates of the
      contribution of FFM to the differences in weight. CONCLUSION: Treatment of HIV
      infection with ARV may affect the interpretation of 10% weight loss.

PMID- 16095766
TI  - Safety and immunogenicity of an oral, inactivated, whole-cell vaccine for
      Shigella sonnei: preclinical studies and a Phase I trial.
AB  - Orally delivered, inactivated whole-cell vaccines are safe methods of inducing
      local and systemic immunity. To increase surface proteins associated with
      adherence and invasion, Shigella sonnei were grown in BHI broth containing
      deoxycholate. A whole-cell vaccine (SsWC) was then produced by formalin
      inactivation. In pre-clinical studies, the SsWC vaccine was immunogenic and
      protected against S. sonnei-induced keratoconjunctivitis in the guinea pig model.
      In a randomized, double-blind, placebo-controlled, Phase I study, 10 evaluable
      subjects received either three doses of SsWC on Days 0, 14, and 28 (N = 3); five
      doses of SsWC on Days 0, 2, 4, 6, and 28 (N = 4); or placebo (N = 3). Each dose
      contained 2.0 x 10(10) inactivated cells. Serum and fecal antibodies against
      SsWC, LPS, and IpaC were measured by ELISA. A > or = 4-fold increase in titer was
      considered significant. Both SsWC dosing regimens were well tolerated. No fever
      or severe gastrointestinal symptoms were noted by any of the vaccinated subjects.
      Antibody responses were similar in the two dosing groups. Serum IgG or IgA
      responses to SsWC were seen in six of seven vaccinees (86%), to LPS in four of
      seven (57%), and to IpaC in five of seven (61%). Fecal IgA responses to these
      three antigens developed in five of five, three of five, and three of five
      subjects, respectively. Among the seven vaccinees, geometric mean rises in serum
      IgA levels to all three immunogens were significant; IgG increases trended toward
      significance (paired one-tailed t-test). We conclude that SsWC was immunogenic
      and protective in animal studies and well tolerated and immunogenic in a Phase I
      trial.

PMID- 16095767
TI  - The adjuvant effect of levamisole on killed viral vaccines.
AB  - To explore adjuvants that are capable of promoting Th1-biased immune response, we
      investigated the usefulness of levamisole (LMS) as one such adjuvant for two
      different preparations of killed viral vaccines, derived from the foot mouth
      disease virus (FMDV) or the porcine respiratory reproductive syndrome virus
      (PRRSV) and tested respectively in BALB/c or C57 BL/6 mice. The results showed
      that LMS induced different types of immune responses in the host, depending on
      its dosage. While a high level of serum IgG was induced by using LMS at 2%, the
      most robust T cell proliferation was induced with LMS at 0.5%. The Th1 and Th2
      cytokine profiles, which tracked well with the antibody and T cell responses,
      were similarly influenced by the dose of LMS. Moreover, the enhanced T cell
      response correlated with increased expression of MHC and co-stimulatory molecules
      and decreased expression of the suppressors of cytokine signaling molecules
      (SOCS1 and SOCS3) in the spleen, suggesting that it is mediated by the antigen
      presentation, co-stimulator signaling, and cytokine production pathways. These
      results establish that LMS can be used to induce Th1-biased immune responses when
      combined with killed-virus-based antiviral vaccines and that such adjuvant effect
      depends on the optimal LMS dosage.

PMID- 16095769
TI  - DNA vaccines against enteric infections.
AB  - The first DNA vaccines for prevention of infectious diseases were described in
      1993 and have since been shown to generate protective humoral and cellular immune
      responses to numerous infectious agents. For enteric infections, protective
      immunity has been obtained with DNA vaccines against several enteric viral,
      bacterial, and parasitic agents. Inoculation of DNA vaccines has generally been
      by intramuscular injection or by gene gun delivery of vaccine DNA-coated gold
      microparticles into the skin. Administration of DNA vaccines by the oral route
      would target the vaccines to enteric mucosal tissues, as well as providing a
      convenient means for vaccine delivery. Orally administered plasmid DNAs
      encapsulated in polymeric microparticles or inserted in live bacterial vectors
      have been effective in animal models for rotavirus DNA vaccines and Listeria
      monocytogenes DNA vaccines, respectively. Human trials of enteric DNA vaccines
      have not been initiated, but trials of veterinary vaccines have shown promise.

PMID- 16095768
TI  - Multi-envelope HIV-1 vaccine devoid of SIV components controls disease in
      macaques challenged with heterologous pathogenic SHIV.
AB  - A central obstacle to the design of a global HIV-1 vaccine is virus diversity.
      Pathogen diversity is not unique to HIV-1, and has been successfully conquered in
      other fields by the creation of vaccine cocktails. Here we describe the testing
      of an HIV-1 envelope cocktail vaccine. Six macaques received the vaccine,
      delivered by successive immunizations with recombinant DNA, recombinant vaccinia
      virus and recombinant envelope proteins. Following vaccination, animals developed
      a diversity of anti-envelope antibody binding and neutralizing activities toward
      proteins and viruses that were not represented by sequence in the vaccine. T
      cells were also elicited, as measured by gamma-interferon production assays with
      envelope-derived peptide pools. Vaccinated and control animals were then
      challenged with the heterologous pathogenic SHIV, 89.6P. Vaccinated monkeys
      experienced significantly lower virus titers and better maintenance of CD4+ T
      cells than unvaccinated controls. The B- and T-cell immune responses were far
      superior post-challenge in the vaccinated group. Four of six vaccinated animals
      and only one of six control animals survived a 44-week observation period post
      challenge. The present report is the first to describe pathogenic SHIV disease
      control mediated by a heterologous HIV-1 vaccine, devoid of 89.6 or SIV
      derivatives.

PMID- 16095770
TI  - Radioactive contamination in urban areas.

PMID- 16095771
TI  - Review of dynamical models for external dose calculations based on Monte Carlo
      simulations in urbanised areas.
AB  - After an accidental release of radionuclides to the inhabited environment the
      external gamma irradiation from deposited radioactivity contributes significantly
      to the radiation exposure of the population for extended periods. For evaluating
      this exposure pathway, three main model requirements are needed: (i) to calculate
      the air kerma value per photon emitted per unit source area, based on Monte Carlo
      (MC) simulations; (ii) to describe the distribution and dynamics of radionuclides
      on the diverse urban surfaces; and (iii) to combine all these elements in a
      relevant urban model to calculate the resulting doses according to the actual
      scenario. This paper provides an overview about the different approaches to
      calculate photon transport in urban areas and about several dose calculation
      codes published. Two types of Monte Carlo simulations are presented using the
      global and the local approaches of photon transport. Moreover, two different
      philosophies of the dose calculation, the "location factor method" and a
      combination of relative contamination of surfaces with air kerma values are
      described. The main features of six codes (ECOSYS, EDEM2M, EXPURT, PARATI, TEMAS,
      URGENT) are highlighted together with a short model-model features
      intercomparison.

PMID- 16095772
TI  - Long-term stability of decontamination effect in recreational areas near the town
      Novozybkov, Bryansk Region, Russia.
AB  - In 1995 and 1997, experimental decontamination campaigns were carried out in two
      recreational areas, Novie Bobovichi and Guta-Muravinka, near the town of
      Novozybkov, Bryansk Region, Russia. These areas were strongly affected by the
      Chernobyl fallout in 1986. In order to examine the long-term stability of the
      clean-up procedures, a programme has been carried out to continuously monitor the
      radiological situation in and around the decontaminated areas. This follow-up
      program consists of regular (1-3 times per year) measurements of absorbed gamma
      dose rate in air (DR) at reference indoor and outdoor locations, repeated DR
      measurements on a grid, and gamma-spectrometric analysis of soil and other
      environmental samples. Very similar dynamics of the Chernobyl-related DR, mostly
      attributed to radiocaesium decay, were found in all the locations. For the period
      under study (September 1995-May 2003), the half-lives (years) for the reduction
      in radiocaesium-dependent DR contribution due to contaminant migration (in the
      following termed 'DRM half-lives') were, respectively, 52+/-26, 57+/-23, 43+/-21,
      46+/-15, and 80+/-56 for the following locations: untreated outdoors, treated
      outdoors, untreated indoors, treated indoors, and undisturbed forest-grassland
      plots outside the recreational areas. These relatively high values of the current
      DRM half-lives correspond very well with the results of soil core analyses, which
      showed no time-dependent changes in the mean mass depths of the (137)Cs
      distribution, neither at treated nor at undisturbed plots. The following signs of
      natural restoration of the disturbed forest-meadow ecosystems have been observed
      at treated areas: formation of a new litter layer, development of grassy spots,
      mushroom growths and new generations of pines and birches. The levels of the
      (137)Cs content in grass and mushrooms from treated plots were one or two orders
      of magnitude lower, than those registered in the samples from untreated areas.
      The follow-up study demonstrates the long-term stability and efficiency of the
      decontamination carried out. There are two main reasons for the sustainment of
      the effects: careful implementation of adequate clean-up procedures and natural
      strong fixation of radiocaesium in soil-associated matrices of the ecosystems.

PMID- 16095773
TI  - MUD: a Model to investigate the migration of 137Cs in the Urban environment and
      Drainage and sewage treatment systems.
AB  - A model is presented for the migration of 137Cs in the urban environment,
      including the drainage systems and the sewage treatment plants, with flexibility
      to be adapted to different configurations common in urban areas. The dynamics of
      137Cs is simulated both under natural evolution and in case of forced
      decontamination, which can have a direct impact on the radioactivity going to
      sewers. The model assesses the activity concentrated in sewage sludge and that
      discharged with the treated or untreated effluent to the receiving watercourse.
      Tests made for two post-Chernobyl contamination scenarios in Sweden show
      differences between model predictions and observed results within the range of
      the experimental uncertainties. An uncertainty and sensitivity analysis of the
      main model parameters indicates that some parameters may have a significant
      influence on the results of the model. Moreover, the model uncertainty is driven
      by a few parameters; therefore, additional research could be necessary into these
      parameters, aiming at simplifying the model without losing its predictive power.

PMID- 16095774
TI  - Finnish workshop on the restoration of contaminated residential areas after a
      nuclear accident: strategy generation and impact assessment.
AB  - Scenario-focused workshops on the restoration of contaminated residential areas
      are planned in a number of European countries within the EVATECH project of the
      EU's Fifth Framework Programme. The intention is to identify factors driving
      decision-making, explore the kinds of strategies that might be appropriate,
      develop methods for stakeholder involvement, and reveal information needs. The
      scenario of the Finnish workshop is presented. A policy generation scheme is
      proposed that yields a manageable but feature-rich set of strategies that is not
      constraint by lack of feasibility, justification, or public acceptability. The
      scheme rests on the premise that the affected area is divided into zones
      according to the level of contamination and that clean-up actions are applied in
      any combination and in combination with relocation.

PMID- 16095775
TI  - Gamma-dose rates from terrestrial and Chernobyl radionuclides inside and outside
      settlements in the Bryansk Region, Russia in 1996-2003.
AB  - In order to estimate current external gamma doses to the population of the
      Russian territories contaminated as a result of the Chernobyl accident, absorbed
      gamma-dose rates in air (DR) were determined at typical urban and suburban
      locations. The study was performed in the western districts of the Bryansk Region
      within the areas of 30 settlements (28 villages and 2 towns) with the initial
      levels of 137Cs deposition ranging from 13 to 4340 kBqm(-2). In the towns, the
      living areas considered were private one-story wooden and stone houses. DR values
      were derived from in situ measurements performed with the help of gamma
      dosimeters and gamma-spectrometers as well as from the results of soil samples
      analysis. In the areas under study, the values of DR from terrestrial
      radionuclides were 25+/-6, 24+/-5, 50+/-10, 32+/-6, 54+/-11, 24+/-8, 20+/-6, 25+/
      8, and 18+/-5 nGyh(-1) at locations of kitchen gardens, dirt surfaces, asphalt
      surfaces, wooden houses, stone houses, grasslands inside settlement, grasslands
      outside settlement, ploughed fields, and forests, respectively. In 1996-2001,
      mean normalized (per MBqm(-2) of 137Cs current inventory in soil) values of DR
      from (137)Cs were 0.41+/-0.07, 0.26+/-0.13, 0.15+/-0.07, 0.10+/-0.05, 0.05+/
      0.04, 0.48+/-0.12, 1.04+/-0.22, 0.37+/-0.07, and 1.15+/-0.19 microGyh(-1) at the
      locations of kitchen gardens, dirt surfaces, asphalt surfaces, wooden houses,
      stone houses, grasslands inside settlement, grasslands outside settlement,
      ploughed fields, and forests, respectively. The radiometric data from this work
      and the values of occupancy factors determined for the Russian population by
      others were used for the assessments of annual effective doses to three selected
      groups of rural population. The normalized (per MBqm(-2) 137Cs current ground
      deposition) external effective doses to adults from 137Cs ranged from 0.66 to
      2.27 mSvy(-1) in the years 1996-2001, in accordance with professional activities
      and structures of living areas. For the areas under study, the average external
      effective doses from 137Cs were estimated to be in the range of 0.39-1.34 mSvy(
      1) in 2001. The average external effective doses from natural radionuclides
      appeared to be lower than those from the Chernobyl fallout ranging from 0.15 to
      0.27 mSvy(-1).

PMID- 16095776
TI  - Measures of health-related quality of life and functional status in survivors of
      oral cavity cancer who have had defects reconstructed with radial forearm free
      flaps.
AB  - The aim of this study was to evaluate (by postal questionnaire) quality of life
      and function in patients who have had resections of oral cancer and
      reconstruction by radial forearm flaps. Between October 1987 and December 2002,
      258 patients had reconstructions by radial forearm flaps after resection of
      tumours in the oral cavity. Of these, 139 surviving patients were identified from
      the database and were sent questionnaires comprising five sections: Functional
      Assessment of Cancer Therapy-General (FACT-G) and -Head and Neck (FACT-HN);
      University of Washington Quality of Life Scale (UWQoL); Performance Status Scale
      for Head and Neck Cancer (PSS-HN); and the final section addressed dental
      rehabilitation and morbidity at the donor site. Sixty-three questionnaires (45%)
      were returned. In 17 (27%), parts of the questionnaire were incomplete. The
      median UWQoL score was 623/900, FACT-G was 92/108, FACT-HN was 31/48, and PSS-HN
      showed that eating in public, understandability of speech and normality of diet
      were 75/100, 75/100 and 50/100, respectively. The effect of stage and site on
      quality of life and function did not reach statistical significance. The effect
      of radiotherapy on speech (p=0.036) and diet (p=0.007) was significant. Patients
      who worried about their cancer returning had a lower UWQoL score (p=0.016).
      Ninety percent regarded their arm as disfigured, but 81% felt comfortable wearing
      short-sleeved shirts. Sensation and function of the hand were reported as normal
      in 87 and 92%, respectively. We conclude that patients who have had oral cancer
      have a persistent reduction in quality of life and function long after completion
      of treatment. The effects can be assessed by postal questionnaire, but the low
      rate of return (45%) and difficulties with completion reduce the quality of the
      data. Quality of life and function are essential components of improvements in
      outcome.

PMID- 16095777
TI  - Computer-assisted reconstruction of orbital floor based on cone beam tomography.
AB  - We used a navigation system for computer-assisted preoperative planning based on
      cone beam tomography with virtual reconstruction to obtain symmetry of the orbit
      and intraoperative control of virtual contours. In operations for reconstruction
      of the orbital floor this technique offers a reliable intraoperative control in
      an area of limited exposure and visibility. There was no significant difference
      in visualisation of anatomical structures between the cone beam tomographic
      digital imaging and communication (DICOM) data and computed tomographic data.
      Cone beam tomography seems to be suitable for computer-assisted planning in the
      management of orbital trauma with reduced costs and less radiation.

PMID- 16095778
TI  - Vascularity and expression of vascular endothelial growth factor in oral squamous
      cell carcinoma, resection margins, and nodal metastases.
AB  - The role of vascularity as a predictor of the likelihood of lymph node metastases
      in oral cancer is not clear. To that end, the vascularity and expression of
      vascular endothelial growth factor (VEGF) was assessed at three specific regions:
      the tumour (inside and around the tumour); the resection margin; and the regional
      lymph nodes. Formalin-fixed paraffin-embedded specimens from 26 oral cancers (11
      with no involved nodes and 15 with involved nodes) were stained
      immunohistochemically and examined. Staining for VEFG was significantly greater
      in the tumour than in the other sites. No significant differences were found in
      the intensity of staining in the primary tumour, resection margins, or nodes
      between cases in which the nodes were involved and in which they were not
      involved. We found no correlation between vascularity and VEGF staining,
      suggesting that VEGF is not the primary or only stimulator of angiogenesis in
      oral cancer. Greater understanding of the mechanisms of metastasis will lead to
      new treatments. The evidence that is accumulating for oral cancer suggests that
      such treatments may be better targeted at preventing lymphatic spread, rather
      than vascular spread.

PMID- 16095779
TI  - Surgical efficacy of carpal tunnel release for carpal tunnel syndrome in
      acromegaly: report of four patients.
AB  - Although carpal tunnel syndrome is frequent in acromegaly, few acromegalics will
      be encountered by most hand surgeons. This paper considers the treatment of four
      cases of acromegaly in whom carpal tunnel syndrome arose, to discuss aspects of
      management of carpal tunnel syndrome in this patient group.

PMID- 16095780
TI  - Ipsilateral shoulder and elbow replacements: on the risk of periprosthetic
      fracture.
AB  - BACKGROUND: Ipsilateral shoulder and elbow replacements may leave only a short
      segment of bone bridging the two implants in the humerus. The potential for high
      stress concentrations as a result of this geometry has been a concern with regard
      to periprosthetic fracture, especially with osteoporotic bone. The study aims to
      determine the optimum length of the bone-bridge between shoulder and elbow
      humeral implants, and to assess the effect of filling the canal with cement.
      METHODS: A three-dimensional finite element model was used to compare the
      stresses between a humerus with a solitary prosthesis and a humerus with both
      proximal and distal cemented prostheses. The length of the bone-bridge and the
      effect of filling the canal with cement were studied under bending and torsion.
      FINDINGS: Gradual load transfer from prosthesis to bone was observed for all
      cases, and no stress concentration was evident. The length of the bone-bridge had
      no deleterious effect on stresses in the humerus, and filling the canal with
      cement did not appreciably decrease the loads carried by the humerus.
      INTERPRETATION: The length of the bone-bridge between stem tips has little effect
      on the resultant stresses in the humerus. Filling the canal with cement adds
      little benefit to the structural integrity of the humerus. Ipsilateral shoulder
      and elbow prostheses may be considered independent of one another in terms of
      risk of periprosthetic fracture.

PMID- 16095781
TI  - Influence of thoracic ramping on whiplash kinematics.
AB  - BACKGROUND: Some experimental whiplash investigations using human volunteers and
      full-body cadavers reported thoracic ramping, characterized by superior
      translation and extension rotation of the cervico-thoracic junction. The effect
      of this phenomenon on cervical spinal kinematics has not been quantitatively
      determined. METHODS: A comprehensively validated computational model exercised in
      2.7 m/s rear impact was used to determine effects of superior translation and
      extension rotation of T1 on cervical segmental kinematics during the retraction
      phase. FINDINGS: In general, thoracic ramping had a minimal effect on cervical
      intervertebral kinematics during retraction. INTERPRETATION: Results of the
      present study demonstrated that magnitude of thoracic ramping plays a minimal
      role in the whiplash injury mechanism due to decreased effect on cervical
      segmental kinematics.

PMID- 16095782
TI  - Delay of intracortical bone remodelling following a stress change: a theoretical
      and experimental study.
AB  - BACKGROUND: A theoretical model and an experimental setup were specifically
      designed to identify and determine the delay of the cortical bone response
      (restricted to mineralization and demineralization) to a stress change. METHODS:
      The in vivo experiment considered two groups of rats: a running group and a
      control sedentary group. The running group rats were compelled to a running
      activity for 15 weeks, followed by a sedentary activity for 15 weeks. Bone
      density was derived from hardness measurements. The parameters of the remodelling
      theory, including the response delay and the remodelling rates, were determined
      from these experimental measurements. FINDINGS: Bone density increased
      significantly during the activity period, and decreased rapidly when rats
      returned to sedentary state. The identification of the model's parameters
      produced evolution curves that were within the limits of the standard deviation
      of the experimental data. The densification rate was lower than the resorption
      rate, and the densification delay was greater than bone resorption delay.
      INTERPRETATION: The delays determined with this macroscopic model are related to
      response delays due to biological internal processes in bone.

PMID- 16095783
TI  - Effect of bone char application on Pb bioavailability in a Pb-contaminated soil.
AB  - The effects of bone char (BC) application on the bioavailability of Pb in a
      polluted soil from Hunan Province, China were examined. The Pb-contaminated soil
      was treated with two types of bone char, one from the UK and the other from
      China. The bioavailability of Pb was determined in terms of the uptake by Chinese
      cabbage (Brassica chinensis L.), sequential extraction and X-ray diffraction
      analysis. The results indicate that the Pb concentrations in both shoots and
      roots decreased with increasing quantities of added bone char, and the
      application of BC from the UK at the rate of 1.6% (w:w) had the largest effect.
      Lead Pb concentrations in the shoots and roots decreased by 56.0% and 75.9%,
      respectively, whereas the application of BC from Zhejiang Province, China at the
      rate of 1.6% (w:w) reduced Pb concentrations in the shoots and roots to 2.04
      mgkg(-1) and 8.42 mgkg(-1), respectively, only 45.8% and 30.2% compared to the
      control treatment. Sequential extraction results indicate that the addition of
      bone char, as a metal-immobilizing agent, substantially transforms soil Pb from
      non-residual fractions to the residual fraction. The transformation was further
      confirmed using X-ray diffraction studies.

PMID- 16095784
TI  - GC and GC-MS characterization of crude oil transformation in sediments and
      microbial mat samples after the 1991 oil spill in the Saudi Arabian Gulf coast.
AB  - The massive oil discharge in the Saudi Arabian coast at the end of the 1991 Gulf
      War is used here as a natural experiment to study the ability of microbial mats
      to transform oil residues after major spills. The degree of oil transformation
      has been evaluated from the analysis of the aliphatic and aromatic hydrocarbons
      by gas chromatography (GC) and GC coupled to mass spectrometry (GC-MS). The oil
      polluted microbial mat samples from coastal environments exhibited an
      intermediate degree of transformation between that observed in superficial and
      deep sediments. Evaporation, photo-oxidation and water-washing seemed to lead to
      more effective and rapid elimination of hydrocarbons than cyanobacteria and its
      associated microorganisms. Furthermore, comparison of some compounds (e.g.
      regular isoprenoid hydrocarbons or alkylnaphthalenes) in the oil collected in the
      area after the spill or in the mixtures retained by cyanobacterial growth gave
      rise to an apparent effect of hydrocarbon preservation in the microbial mat
      ecosystems.

PMID- 16095785
TI  - Why do young people drink? A review of drinking motives.
AB  - This article reviews evidence of adolescent and young adult drinking motives and
      their relation to possible consequences over the last 15 years. To this end, a
      computer-assisted search of relevant articles was conducted. Results revealed
      that most young people reported drinking for social motives, some indicated
      enhancement motives, and only a few reported coping motives. Social motives
      appear to be associated with moderate alcohol use, enhancement with heavy
      drinking, and coping motives with alcohol-related problems. However, an enormous
      heterogeneity was found in terms of how motives were measured: 10 to 40 items
      were grouped into between 2 and 10 dimensions and sometimes the same items
      occurred under different dimensions. Future studies should therefore use well
      defined, theoretically based, homogenous instruments to disentangle cultural from
      measurement differences across surveys.

PMID- 16095786
TI  - An implementation intentions intervention, the use of a planning strategy, and
      physical activity after myocardial infarction.
AB  - The paper investigates the relations between involvement in an implementation
      intention intervention programme, frequency of the use of a self-regulatory
      physical activity planning strategy, and moderate physical activity among
      patients who had suffered myocardial infarction (MI). It examines whether effects
      of the implementation intention intervention on behavior change was mediated by
      change in the use of a planning strategy. A total of 114 patients from central
      and northern Poland took part in the study after their first uncomplicated MI.
      Data were collected individually at approximately 1 week after MI (Time 1), 2
      weeks after short-term rehabilitation (about 8 weeks after MI: Time 2), and 8
      months after MI (Time 3). After data collection at Time 2, patients were randomly
      assigned to the control group or the intervention group. Patients who
      participated in the implementation intention intervention maintained the same
      number of sessions of moderate physical activity at 8 months after MI (Time 3) as
      at 2 weeks after rehabilitation (Time 2). By contrast, patients from the control
      group performed significantly fewer sessions of moderate physical activity at
      Time 3, compared to Time 2. The intervention resulted in the more frequent use of
      a planning strategy at 8 months after MI. Change in the frequency of the use of a
      planning strategy completely mediated effects of the intervention on change in
      physical activity. Only patients who participated in the implementation intention
      intervention and increased their use of a planning strategy adhered to the
      recommended three or more sessions of moderate physical activity per week.

PMID- 16095787
TI  - Psychometric and cognitive validation of a social capital measurement tool in
      Peru and Vietnam.
AB  - Social capital is a relatively new concept which has attracted significant
      attention in recent years. No consensus has yet been reached on how to measure
      social capital, resulting in a large number of different tools available. While
      psychometric validation methods such as factor analysis have been used by a few
      studies to assess the internal validity of some tools, these techniques rely on
      data already collected by the tool and are therefore not capable of eliciting
      what the questions are actually measuring. The Young Lives (YL) study includes
      quantitative measures of caregiver's social capital in four countries (Vietnam,
      Peru, Ethiopia, and India) using a short version of the Adapted Social Capital
      Assessment Tool (SASCAT). A range of different psychometric methods including
      factor analysis were used to evaluate the construct validity of SASCAT in Peru
      and Vietnam. In addition, qualitative cognitive interviews with 20 respondents
      from Peru and 24 respondents from Vietnam were conducted to explore what each
      question is actually measuring. We argue that psychometric validation techniques
      alone are not sufficient to adequately validate multi-faceted social capital
      tools for use in different cultural settings. Psychometric techniques show SASCAT
      to be a valid tool reflecting known constructs and displaying postulated links
      with other variables. However, results from the cognitive interviews present a
      more mixed picture with some questions being appropriately interpreted by
      respondents, and others displaying significant differences between what the
      researchers intended them to measure and what they actually do. Using evidence
      from a range of methods of assessing validity has enabled the modification of an
      existing instrument into a valid and low cost tool designed to measure social
      capital within larger surveys in Peru and Vietnam, with the potential for use in
      other developing countries following local piloting and cultural adaptation of
      the tool.

PMID- 16095788
TI  - Disciplining the feminine: the reproduction of gender contradictions in the
      mental health care of women with eating disorders.
AB  - This paper provides insights into the way gendered assumptions operate within
      health care interventions for women with eating disorders. A multidisciplinary
      sample of Australian health care workers were interviewed about their approaches
      to treatment, and discourse analysis was used to uncover the discursive dynamics
      and power relations characterising their accounts of intervention. The paper
      demonstrates a contradictory positioning of anorexic patients in relation to
      autonomy and control within the two common psychiatric interventions of bed rest
      intervention and psychotherapy. The paper argues that this is based on gendered
      assumptions about selfhood and femininity in eating disorders that are reproduced
      in the therapeutic relationship through the operation of a gendered parent-child
      dynamic, with the health care worker as father or mother, and the anorexic
      patient as daughter. One of the main effects of this is to re-inscribe rather
      than challenge the discursive 'double bind' of femininity that has been widely
      implicated by post-structural feminists in producing eating disorders in the
      first place. The paper also considers the widely acknowledged problem of
      resistance to treatment in anorexia as a function of controlling treatments, and
      discusses psychiatrists' perspectives on addressing this dilemma. Finally, the
      paper examines the potential of feminist-informed understandings of eating
      disorders for overcoming the gendered dilemmas inherent within the dominant
      psycho-medical treatment paradigm.

PMID- 16095789
TI  - A conceptually based approach to understanding chronically ill patients'
      responses to medication cost pressures.
AB  - Prescription medications enhance the well-being of most chronically ill patients.
      Many individuals, however, struggle with how to pay for their treatments and as a
      result experience problems with self-care and health maintenance. Although
      studies have documented that high out-of-pocket costs are associated with
      medication non-adherence, little research on prescription cost sharing has been
      theoretically grounded in knowledge of the more general determinants of patients'
      self-management behaviors and chronic disease outcomes. We present a conceptual
      framework for understanding the influence of patient, medication, clinician, and
      health system factors on individuals' responses to medication costs. We review
      what is known about how these factors influence medication adherence, identify
      possible strategies through which clinicians, health systems, and policy-makers
      may assist patients burdened by their medication costs, and highlight areas in
      need of further research. Although medication costs represent a burden to
      chronically ill patients worldwide, most patients report using their medication
      as prescribed despite the costs, and others report cost-related underuse despite
      an apparent ability to afford those treatments. The cost-adherence relationship
      is modified by contextual factors, including patients' characteristics (e.g.,
      age, ethnicity, and attitudes toward medications), the type of medications they
      are using (e.g., the complexity of dosing and the drug's clinical target),
      clinician factors (e.g., choice of first-line agent and communication about
      medication costs), and health system factors (e.g., efforts to influence
      clinicians' prescribing and to help patients apply for financial assistance
      programs). Understanding these relationships will enable clinicians and policy
      makers to better design pharmacy benefits and assist patients in taking their
      medication as prescribed. The next generation of studies examining the
      consequences of prescription drug costs should expand our knowledge of the ways
      in which these co-factors influence patients' responses to medication cost
      pressures.

PMID- 16095790
TI  - Schizophrenia and single-carbon metabolism.
AB  - Schizophrenic patients generally appear to have a disturbed single-carbon
      metabolism. Methionine and homocysteine are intermediary metabolites in this
      metabolic system. In a case-control study of the cerebrospinal fluid, a majority
      of the patients had elevated methionine and a smaller subgroup had elevated
      homocysteine. Elevated homocysteine is often explained by folate dependency due
      to mutations in the gene for methylenetetrahydrofolate reductase (MTHFR). A most
      encouraging feature of single-carbon metabolism is its potential modification by
      natural means, such as B-vitamins and antioxidants. The findings point to a new
      area of schizophrenia research: the role of nutrients and antioxidants for
      rational prevention and treatment.

PMID- 16095791
TI  - A subchronic toxicity study of dunaliella carotene in F344 rats.
AB  - Dunaliella carotene, extracted from dunaliella alga (Dunaliella bardawil or
      Dunaliella salina), for use as a food-coloring agent, has beta-carotene as its
      mainly constituent. As there have been no reports of toxicological evaluation, a
      90-day subchronic toxicity study was here performed in F344 rats at dose levels
      of 0 (control), 0.63%, 1.25%, 2.5% and 5% in powdered basal diet. The average
      daily intakes of dunaliella carotene were 352, 696, 1420 and 2750 mg/kg/day,
      respectively, for males, and 370, 748, 1444 and 2879 mg/kg/day for females. No
      mortality or treatment-related clinical signs were observed throughout the
      experimental period in any of the groups. Body weight gain was slightly but
      significantly (p < 0.05) reduced from week 5 to the end of the experiment in 2.5%
      and 5% males. Increased PLT were observed in 1.25% and 5% males, and 2.5% and 5%
      females. Significant elevations or tendencies for increase in serum T. Cho and Ca
      were observed in all treated males and females, with clear dose-dependence in
      males. Organ weight measurement and histopathological observation revealed no
      toxicological changes. Based on growth suppression, no-observed-adverse-effect
      levels (NOAELs) were estimated to be 1.25% (696 mg/kg/day) for males and 5% (2879
      mg/kg/day) for females. As increases in serum Ca were observed in the lowest
      group in both sexes, a no-observed-effect level (NOEL) could not be determined in
      this study.

PMID- 16095792
TI  - Characterization of alkyl phenols in cashew (Anacardium occidentale) products and
      assay of their antioxidant capacity.
AB  - In this study the content of anacardic acids, cardanols and cardols in cashew
      apple, nut (raw and roasted) and cashew nut shell liquid (CNSL) were analysed.
      The higher amounts (353.6 g/kg) of the major alkyl phenols, anacardic acids were
      detected in CNSL followed by cashew fibre 6.1 g/kg) while the lowest (0.65 g/kg)
      amounts were detected in roasted cashew nut. Cashew apple and fibre contained
      anacardic acids exclusively, whereas CNSL also contained an abundance of
      cardanols and cardols. Cashew nut (raw and roasted) also contained low amounts of
      hydroxy alkyl phenols. Cashew nut shell liquid was used for a basic fractionation
      of the alkyl phenol classes and the individual anacardic acids, major cardanols
      and cardols were purified to homogeneity from these fractions by semi-preparative
      HPLC and definitively identified by nano-ESI-MS-MS, GC-MS and NMR analyses. The
      hexane extracts (10 mg/ml) of all cashew products tested plus CNSL, displayed
      significant antioxidant capacity. Cashew nut shell liquid was the more efficient
      (inhibition=100%) followed by the hexane extract of cashew fibre (94%) and apple
      (53%). The antioxidant capacity correlated significantly (P<0.05) with the
      concentration of alkyl phenols in the extracts. A mixture of anacardic acids
      (10.0 mg/ml) showed the higher antioxidant capacity (IC50=0.60 mM) compared to
      cardols and cardanols (IC50>4.0 mM). The data shows that of these substances,
      anacardic-1 was by far the more potent antioxidant (IC50=0.27 mM) compared to
      cardol-1 (IC50=1.71 mM) and cardanol-1 (IC50>4.0 mM). The antioxidant capacity of
      anacardic acid-1 is more related to inhibition of superoxide generation
      (IC50=0.04 mM) and xanthine oxidase (IC50=0.30 mM) than to scavenging of hydroxyl
      radicals. At present a substantial amount of cashew fibre is mostly used in
      formulations of animal or poultry feeds. The data presented in this study,
      indicates that this waste product along with CNSL, both of which contain high
      contents of anacardic acids, could be better utilized in functional food
      formulations and may represent a cheap source of cancer chemopreventive agents.

PMID- 16095793
TI  - Effect of diphenyl diselenide, diphenyl ditelluride and ebselen on cerebral
      Na(+), K(+)-ATPase activity in rats.
AB  - In the present study, we investigated the in vitro effect of diphenyl
      ditelluride, diphenyl diselenide and ebselen on Na(+), K(+)-ATPase activity of
      rat brain. The results demonstrated that all compounds significantly inhibited
      (in the muM range) Na(+), K(+)-ATPase activity. Diphenyl ditelluride, at low
      concentrations, provoked an increase in Na(+), K(+)-ATPase activity.
      Dithiothreitol (DTT), at 3mM, protected the inhibition caused by diphenyl
      ditelluride, diphenyl diselenide and ebselen in Na(+), K(+)-ATPase activity. Post
      incubation of diphenyl diselenide-treated homogenate with DTT completely
      recovered enzyme activity. DTT was able to recover the enzyme inhibition induced
      by 20muM of diphenyl ditelluride, but was partially able to recover inhibition
      induced by high concentrations of organotellurium compound. Conversely, DTT did
      not recover ebselen-induced Na(+), K(+)-ATPase inhibition. The mechanism of
      inhibition by diphenyl diselenide, diphenyl ditelluride and ebselen in Na(+),
      K(+)-ATPase activity revealed: decreased maximal velocity and K(m). Cerebral
      Na(+), K(+)-ATPase is a potential molecular target for the toxic effect of
      organochalcogens and the inhibition may occur through a change in the crucial
      thiol groups of this enzyme.

PMID- 16095794
TI  - Restraint stress does not enhance the uranium-induced developmental and
      behavioral effects in the offspring of uranium-exposed male rats.
AB  - The influence of stress on postnatal development and behavior was assessed in the
      offspring of male rats exposed to uranium (U). Eight groups of adult animals
      received uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 10,
      20 and 40 mg/kg/day during 3 months. One half of rats in each group were
      concurrently subjected to restraint stress during 2 h per day throughout the
      study. At the end of the experimental period, male rats were mated with untreated
      females (1:2). On gestation day 14, one half of pregnant rats were euthanized in
      order to evaluate maternal toxicity and gestational parameters. The remaining
      dams were allowed to deliver and wean their offspring. Pups were evaluated for
      physical development, neuromotor maturation, as well as for behavioral effects.
      Restraint significantly increased the gravid uterine weight at 40 mg/kg/day.
      However, no significant interactions between restraint and U could be established
      in the remaining parameters of maternal toxicity. In the offspring, no remarkable
      effects of U, restraint or their combination were noted on developmental
      landmarks, or in the passive avoidance and water maze test. It is concluded that
      at the current U doses, restraint stress did not enhance the few uranium-induced
      physical, neuromotor and behavioral changes in the offspring of UAD-exposed male
      rats.

PMID- 16095795
TI  - Effects of an impedance threshold valve upon hemodynamics in Standard CPR:
      studies in a refined computational model.
AB  - An impedance threshold valve (ITV) is a new airway adjunct for resuscitation that
      permits generation of a small vacuum in the chest during the recoil phase of
      chest compression. OBJECTIVES: To explore in detail the expected magnitude and
      the hemodynamic mechanisms of circulatory augmentation by an ITV in Standard CPR.
      METHOD: A 14-compartment mathematical model of the human cardiopulmonary system-
      upgraded to include applied chest compression force, elastic recoil of the chest
      wall, anatomic details of the heart and lungs, and the biomechanics of
      mediastinal compression--is exercised to explore the conditions required for
      circulatory augmentation by an ITV during various modes of CPR. RESULTS: The ITV
      augments systemic perfusion pressure by about 5 mmHg compared to any particular
      baseline perfusion pressure without the ITV. When baseline perfusion is low,
      owing to either diminished chest compression force, the existence of a thoracic
      pump mechanism of blood flow, or the presence of an effective compression
      threshold, then the relative improvement produced by an ITV is significant. With
      an ITV the heart expands into soft pericardiac tissue, which makes the heart
      easier to compress. CONCLUSIONS: An ITV can augment perfusion during CPR. The
      observed effectiveness of ITVs in the laboratory and in the clinic suggests a
      thoracic pump mechanism for Standard CPR, and perhaps also an effective
      compression threshold that must be exceeded to generate blood flow by external
      chest compression.

PMID- 16095796
TI  - Effect of transthoracic shocks on left ventricular function.
AB  - Although defibrillating shocks are thought to depress ventricular function
      transiently, the independent effects of high strength shocks (without the
      metabolic sequelae of pre-shock fibrillation) have not been assessed
      systematically in humans. Therefore, we delivered three consecutive synchronized
      monophasic transthoracic shocks (200, 200 and 360 J) at 60s intervals during
      sinus rhythm and evaluated the effect on left ventricular chamber size and
      function as determined by transesophageal echocardiography in 11 patients (mean
      age 67+/-8 years, 9M/2F) with depressed left ventricular function (left
      ventricular ejection fraction: 14-37%). The shocks did not alter hemodynamics
      consistently. On average, the shocks did not alter stroke volume, cardiac output,
      left ventricular ejection fraction or regional wall thickening (all p>0.05 versus
      baseline). This effect was highly variable and 36% of patients experienced a >25%
      reduction in cardiac output by the final shock. There was a tendency for regional
      wall thickening to worsen in the best baseline sextant with an offsetting
      significant increase in thickening in the worst baseline sextant (p=0.05). Thus,
      repetitive defibrillation strength transthoracic shocks do not impair left
      ventricular function consistently in patients with cardiomyopathy. However, the
      effect is widely variable and potentially important depression of left
      ventricular function does occur in some patients.

PMID- 16095797
TI  - The acute coronary syndrome--pre-hospital diagnostic quality.
AB  - BACKGROUND AND OBJECTIVE: In the Austrian emergency medical service (EMS),
      emergency medical technician-staffed and physician-staffed vehicles are in
      operation. Patients with suspected acute coronary syndromes (ACS) are treated in
      the pre-hospital phase and transported to the hospital by an emergency physician
      (EP). This study evaluates the diagnostic performance of EPs in ACS and the
      impact of this emergency system on the outcome of ACS in an urban area. DESIGN:
      Retrospective case control study. METHODS: All protocol sheets from the emergency
      physicians were searched for the diagnosis of ACS. The database of the emergency
      department (ED) was searched for patients with ACS as an admission diagnosis or
      ACS as discharge diagnosis. For patients admitted to an intensive care unit
      (ICU), the medical history from the ICU was reviewed. According to the diagnosis
      and the aggressiveness of therapy, patients were divided in five categories of
      severity at each stage of care (pre-hospital category, ED category, ICU
      category). RESULTS: A total of 3585 patients was analysed. Only 17.8% of the
      patients with ACS as the admission diagnosis and 20.3% of the patients with ACS
      as the discharge diagnosis were transported by an EP. 46.8% of the ACS diagnosis
      by EPs were confirmed in hospital. Patients transported by EPs showed a higher
      all-cause mortality in hospital (1.6% vs. 0.6%; p=0.011). There was no
      significant correlation between the pre-hospital category of patients treated by
      EPs and the ED category. When a 12-lead-electrocardiogram was recorded, the
      correlation improved slightly (rho: 0.139; p=0.006). CONCLUSIONS: The percentage
      of ACS patients transported to hospital by an EP is very low, and EPs seem to be
      "over-aware" in the diagnosis of ACS.

PMID- 16095798
TI  - The effect of reward magnitude differences on choosing disadvantageous decks in
      the Iowa Gambling Task.
AB  - In the Iowa Gambling Task, participants have to develop a long-term profitable
      monetary scenario in a situation of uncertainty and a conflict between the chance
      of encountering an immediate large reward (100 US dollars) in two long-term
      loosing decks (A and B; -250 US dollars per 10 cards) and the chance of
      encountering an immediate small reward (50 US dollars) in two long-term winning
      decks (C and D; +250 US dollars per 10 cards). The ratio of the immediate rewards
      in decks A/B and C/D is thus 2:1. Here, we manipulated these differences in
      reward magnitude between the advantageous (C/D) and disadvantageous (A/B) decks,
      while keeping the net gains and losses per 10 cards the same, to assess the
      impact of the conflict between immediate and distant pay-off on choice behaviour.
      Participants selected less cards from disadvantageous decks and won more money
      when the reward magnitude difference was decreased, A/B:C/D=1:1, while they
      selected more cards from disadvantageous decks and lost more money when reward
      magnitude differences were increased, A/B:C/D=4:1 and 6:1. This study shows that
      the outcome in the Iowa Gambling Task is sensitive to differences between the
      magnitude of immediate rewards in the advantageous and disadvantageous decks.

PMID- 16095799
TI  - The post-orgasmic prolactin increase following intercourse is greater than
      following masturbation and suggests greater satiety.
AB  - Research indicates that prolactin increases following orgasm are involved in a
      feedback loop that serves to decrease arousal through inhibitory central
      dopaminergic and probably peripheral processes. The magnitude of post-orgasmic
      prolactin increase is thus a neurohormonal index of sexual satiety. Using data
      from three studies of men and women engaging in masturbation or penile-vaginal
      intercourse to orgasm in the laboratory, we report that for both sexes (adjusted
      for prolactin changes in a non-sexual control condition), the magnitude of
      prolactin increase following intercourse is 400% greater than that following
      masturbation. The results are interpreted as an indication of intercourse being
      more physiologically satisfying than masturbation, and discussed in light of
      prior research reporting greater physiological and psychological benefits
      associated with coitus than with any other sexual activities.

PMID- 16095800
TI  - Immediate complications of tension-free vaginal tape (TVT): results of a French
      survey.
AB  - BACKGROUND: The aim was to evaluate morbidity following operation using tension
      free vaginal tape (TVT). METHODS: Between June 2002 and June 2003, a
      questionnaire was sent to French gynecologists and urologists. Participants
      reported the number of TVT procedures performed before January 2002, number of
      minor or major pre- and post-operative complications. RESULTS: The questionnaire
      was returned by 92 participants (21 urologists and 71 gynecologists) who reported
      12,280 TVT procedures (median: 100, minimum: 5, maximum: 2100). Overall, 901
      preoperative bladder injuries were reported (7.34%). For 809 patients (6.59%),
      complete post-operative urinary retention requiring catheterization was noted.
      There were 26 cases of vaginal defect healing (0.21%). Retropubic or vulvovaginal
      hematoma was reported for 39 patients (0.32%). Ten major organ injuries were
      reported (0.08%): one obturator nerve injury, three bowel perforations, four
      vessel injuries and two ureteral injuries. CONCLUSION: The risk of major
      complications following the use of tension-free vaginal tape is low. However,
      these potential complications require experienced surgeons for the practice of
      tension-free vaginal tape.

PMID- 16095801
TI  - Evolution of Spanish scientific production in international obstetrics and
      gynecology journals during the period 1986-2002.
AB  - OBJECTIVE: The present bibliometric study analyzes Spanish scientific work
      published in the field of obstetrics and gynecology in the most important
      journals during the period 1986-2002. STUDY DESIGN: The material studied (779
      original documents) was selected in accordance with the science citation index
      (SCI) of 2001, obstetrics and gynecology section, using the EMBASE: Obstetrics
      and Gynecology database. We applied the customary rules of bibliometrics: Price's
      Law of increase in scientific literature, Bradford's Law of scattering of
      scientific literature and Lotka's Law of author productivity. Furthermore, we
      analyzed participation index (PaI), the collaboration index and the superior
      (%SUP). RESULTS: The material studied is closer to an exponential adjustment (r =
      0.958) than to a linear adjustment (r = 0.856). The journal with the largest
      number of originals is Human Reproduction (Bradford's first area), with 217
      articles and that with the highest PaI is Menopause (4.07). The total number of
      authors is 1829, who are responsible for 3938 authorships (2.79% of the authors
      have a productivity index (PI) > or = 1 and 70.09% have a PI = 0). The majority
      of the studies were carried out in hospitals (47.62%) and universities (23.36%).
      CONCLUSION: Spanish productivity in the field of obstetrics and gynecology
      increased considerably in the period 1986-2002.

PMID- 16095802
TI  - Characteristics of tobacco withdrawal in pregnant women.
AB  - OBJECTIVE: To describe the management of tobacco withdrawal in pregnant women.
      STUDY DESIGN: The questionnaire-based, descriptive survey included 979 post
      partum women. The variables analysed included the characteristics of the mother
      and neonate at delivery, her smoking habits, her level of exposure to passive
      smoking, and the barriers to giving up smoking. The chi square test was used to
      analyse qualitative variables and the Students t-test for quantitative variables.
      RESULTS: 76% of women who smoked at the start of pregnancy said that they had
      been asked about their tobacco consumption. However, only 16% had been asked by a
      clinician or midwife about their attempts to stop smoking. Seven percent were
      offered a specialised consultation, but only one-third attended. Seventy-six
      percent of women who failed to stop smoking during pregnancy had a partner who
      smoked compared with 63% of women who gave up. Dependency and stress during
      pregnancy also were lower for women who stopped smoking. CONCLUSIONS: Healthcare
      professionals seems to offer only rudimentary care. Simple strategies to help
      women give up smoking are required. The partner is an important target,
      especially if he can be persuaded to give up at the same time.

PMID- 16095803
TI  - Laparoscopic treatment of endometrial cancer: feasibility and results.
AB  - OBJECTIVE: The aim of this study was to compare laparoscopic and abdominal
      approach in the treatment of endometrial cancer in our department. STUDY DESIGN:
      From January 1999 to November 2002, 77 patients underwent surgery for stages I
      III endometrial cancer. The first group of 36 patients had abdominal hysterectomy
      as well as salpingo-oophorectomy, with or without lymphadenectomy. The remaining
      41 patients received laparoscopic assisted vaginal hysterectomy as well as
      salpingo-oophorectomy, with or without lymphadenectomy. In this retrospective
      study, we have compared the surgical results, the short- and long-term morbidity
      and the outcome of the two patient groups. RESULTS: Body mass index (BMI) was
      significantly higher in the laparoscopic group (27.3 versus 24.6; p=0.009). The
      average time for surgery was significantly longer for the laparoscopic group
      (143.6 min versus 109.7 min; p=0.0001), but lymphadenectomy was performed in more
      patients (63.4% versus 25%; p=0.001). Postoperative hospital stay was
      significantly longer in patients undergoing the abdominal approach (4.59 days
      versus 3.18 days; p<0.0001). No blood transfusions were performed and the rates
      of complications were similar in the two groups. No differences were found in
      recurrence and survival rate. CONCLUSIONS: In our experience, laparoscopic and
      abdominal surgery can achieve similar results in the treatment of endometrial
      cancer. In our series, even with the BMI and the number of lymphadenectomies
      being higher in the laparoscopic group, the rates of complications were similar
      in the two groups.

PMID- 16095804
TI  - Forecasting environmental equity: air quality responses to road user charging in
      Leeds, UK.
AB  - Sustainable development requires that the goals of economic development,
      environmental protection and social justice are considered collectively when
      formulating development strategies. In the context of planning sustainable
      transport systems, trade-offs between the economy and the environment, and
      between the economy and social justice have received considerable attention. In
      contrast, much less attention has been paid to environmental equity, the trade
      off between environmental and social justice goals, a significant omission given
      the growing attention to environmental justice by policy makers in the EU and
      elsewhere. In many countries, considerable effort has been made to develop clean
      transport systems by using, for example, technical, economic and planning
      instruments. However, little effort has been made to understand the distributive
      and environmental justice implications of these measures. This paper investigates
      the relationship between urban air quality (as NO2) and social deprivation for
      the city of Leeds, UK. Through application of a series of linked dynamic models
      of traffic simulation and assignment, vehicle emission, and pollutant dispersion,
      the environmental equity implications of a series of urban transport strategies,
      including road user cordon and distance-based charging, road network development,
      and emission control are assessed. Results indicate a significant degree of
      environmental inequity exists in Leeds. Analysis of the transport strategies
      indicates that this inequity will be reduced through natural fleet renewal, and,
      perhaps contrary to expectations, road user charging is also capable of promoting
      environmental equity. The environmental equity response is, however, sensitive to
      road pricing scheme design.

PMID- 16095805
TI  - The influence of metal source uncertainty on cost-effective allocation of mine
      water pollution abatement in catchments.
AB  - In mine water pollution abatement, it is commonly assumed that known mine waste
      sites are the major pollution sources, thus neglecting the possibility of
      significant contribution from other old and diffuse sources within a catchment.
      We investigate the influence of different types of pollution source uncertainty
      on cost-effective allocation of abatement measures for mine water pollution. A
      catchment-scale cost-minimization model is developed and applied to the catchment
      of the river Dalalven, Sweden, in order to exemplify important effects of such
      source uncertainty. Results indicate that, if the pollution distribution between
      point and diffuse sources is partly unknown, downstream abatement measures, such
      as constructed wetlands, at given compliance boundaries are often cost-effective.
      If downstream abatement measures are not practically feasible, the pollution
      source distribution between point and diffuse mine water sources is critical for
      cost-effective solutions to abatement measure allocation in catchments. In
      contrast, cost-effective solutions are relatively insensitive to uncertainty in
      total pollutant discharge from mine water sources.

PMID- 16095806
TI  - Bottom up and top down: analysis of participatory processes for sustainability
      indicator identification as a pathway to community empowerment and sustainable
      environmental management.
AB  - The modern environmental management literature stresses the need for community
      involvement to identify indicators to monitor progress towards sustainable
      development and environmental management goals. The purpose of this paper is to
      assess the impact of participatory processes on sustainability indicator
      identification and environmental management in three disparate case studies. The
      first is a process of developing partnerships between First Nations communities,
      environmental groups, and forestry companies to resolve conflicts over forest
      management in Western Canada. The second describes a situation in Botswana where
      local pastoral communities worked with development researchers to reduce
      desertification. The third case study details an on-going government led process
      of developing sustainability indicators in Guernsey, UK, that was designed to
      monitor the environmental, social, and economic impacts of changes in the
      economy. The comparative assessment between case studies allows us to draw three
      primary conclusions. (1) The identification and collection of sustainability
      indicators not only provide valuable databases for making management decisions,
      but the process of engaging people to select indicators also provides an
      opportunity for community empowerment that conventional development approaches
      have failed to provide. (2) Multi-stakeholder processes must formally feed into
      decision-making forums or they risk being viewed as irrelevant by policy-makers
      and stakeholders. (3) Since ecological boundaries rarely meet up with political
      jurisdictions, it is necessary to be flexible when choosing the scale at which
      monitoring and decision-making occurs. This requires an awareness of major
      environmental pathways that run through landscapes to understand how seemingly
      remote areas may be connected in ways that are not immediately apparent.

PMID- 16095807
TI  - The application of an indicator based on taxonomic distinctness for UK marine
      biodiversity assessments.
AB  - Mankind needs to use the resources and opportunities offered by the marine
      environment while protecting ecological processes and systems. This is the
      foundation for sustainable development, which can only be achieved by adopting an
      appropriate management approach. Whether internationally or at a regional scale,
      successful management of marine ecosystems needs to be based on a scientifically
      robust approach to monitoring environmental change. Within such a framework, the
      conservation of marine biological diversity is problematic, as many conventional
      measures of diversity are not appropriate for measuring the types of change that
      require management. New indicators are required and in this paper we summarise
      some of the current methodology being used to derive such indices, which may be
      used to evaluate the effectiveness of marine stewardship initiatives. Through a
      series of examples we demonstrate the application of the taxonomic distinctness
      indicator of biodiversity to marine environmental assessment and its development
      towards becoming an operational tool.

PMID- 16095808
TI  - Monitoring of natural and synthetic hormones in a polluted river.
AB  - Natural (estradiol, estrone, testosterone, estriol) and synthetic hormones
      (ethinylestradiol) are constantly excreted into the environment from human and
      animal sources but little is known of their transport. The purpose of this study
      was to determine how far along a 100 km river course that hormones could be
      detected after contamination with sewage effluent or fishpond effluent. Fourteen
      sites in the Lower Jordan River drainage were sampled (two sites above the sewage
      effluent contamination, eight sites below the contamination and four tributaries)
      before and after the dry season of 2002 (Spring and Fall). Samples were tested
      for testosterone, estrogen (estrone and estradiol combined), estriol,
      ethinylestradiol, ammonia and fecal coli. It was found that the fecal coli count
      dropped exponentially (from 250,000 to 60/100 ml3) and the ammonia dropped from
      15 to less than 1mg/l over the initial 25 km stretch. Over the same stretch, the
      hormone values declined by half from their maximum values for testosterone (3.3
      ng/l), estriol (8.8 ng/l), ethinylestradiol (6.1 ng/l), and estrogen (4.9 ng/l).
      From 67 to 100 km mark, testosterone (4.8 ng/l) and estrogen (2.4 ng/l) were
      still elevated while ethinylestradiol and estriol were >or=1.5 ng/l. The high
      level of testosterone and estrogen between 67 and 100 km marks was probably due
      to major discharge from fishponds between 23 and 27 km marks. Levels of
      ethinylestradiol above 1 ng/l, a level which can affect fish, was seen in 70%
      (12/16) of the samples tested. The data suggest that hormones in readily measured
      quantities can be transported considerable distances from the source of
      pollution.

PMID- 16095809
TI  - Expression of cdc25B and cdc25A in medullary thyroid carcinoma: cdc25B expression
      level predicts a poor prognosis.
AB  - Cdc25B and cdc25A phosphatases are prominent stimulators of cell cycle
      progression and have been suggested to play oncogenic roles. In this study, we
      immunohistochemically investigated the expression of these phosphatases in
      medullary thyroid carcinoma. Cdc25B was positive in 35.8% of cases examined. Its
      positivity was linked only to patient age. However, patients with cdc25B-positive
      tumors showed a significantly worse disease-free survival rate (P=0.0210) than
      those with cdc25B-negative tumors. Cdc25A was positive in only 17.2% of cases and
      was not related to clinicopathological parameters or prognosis. These findings
      suggest that cdc25B can be regarded as having prognostic significance and as a
      novel marker of biologically aggressive characteristics in this carcinoma.

PMID- 16095810
TI  - APAF-1 signaling in human melanoma.
AB  - Acquired resistance to mechanisms of programmed cell death is one of the
      hallmarks of cancer. Human melanoma, in advanced stage, is hardly curable, due to
      development of several strategies that impair apoptosis induced by the death
      receptor and the mitochondrial pathways of apoptosis. Among these apoptosis
      escape strategies, one is based on inactivation of pro-apoptotic factors such as
      Apoptotic Protease Activating Factor-1 (APAF-1). APAF-1 couples cytochrome c
      release from the mitochondria to caspase-9 activation and has been considered a
      central adaptor in the intrinsic pathway of programmed cell death. Inactivation
      of APAF-1 in human melanoma may impair the mitochondrial pathway of apoptosis
      induced by chemotherapeutic drugs that activate the p53 pathway, thus
      contributing to the development of chemoresistance. In-vivo, loss of expression
      of APAF-1 is associated with tumor progression, suggesting that APAF-1
      inactivation may provide a selective survival advantage to neoplastic cells.
      However, recent results have indicated the existence of APAF-1-independent
      pathways of caspase activation and apoptosis in normal and neoplastic cells.
      Moreover, it has been found that expression of APAF-1 is not necessary for the
      apoptotic response of melanoma cells to different pro-apoptotic drugs. The
      emerging picture from results obtained in melanoma and other human tumors is that
      the relevance of the APAF-1 pathway in programmed cell death is cell-context
      dependent and related to the specificity of the pro-apoptotic-stimuli.

PMID- 16095811
TI  - The radical scavenger edaravone enhances the anti-tumor effects of CPT-11 in
      murine colon cancer by increasing apoptosis via inhibition of NF-kappaB.
AB  - The transcription factor NF-kappaB is reportedly activated by anti-cancer
      chemotherapeutic compounds in many cancer cell lines and NF-kappaB activation is
      one mechanism by which tumors become resistant to apoptosis. Antioxidants have
      been reported to serve as potent NF-kB inhibitors. In this study, we investigated
      the ability of edaravone to enhance apoptosis induced by CPT-11 through
      inhibition of NF-kB. In vitro, SN38, the active metabolite of CPT-11, induced
      activation of NF-kB, the production of intracellular reactive oxygen species, the
      activation of caspase-3, and apoptosis in colon26 cells. Pretreatment with
      edaravone scavenged the SN38-produced reactive oxygen species, and inhibited the
      SN38-induced activation of NF-kB. Moreover, edaravone enhanced the activation of
      caspase-3, and the level of apoptosis induced by SN38. In vivo, the combination
      of edaravone with CPT-11 reduced subcutaneous tumor growth and number of
      pulmonary metastases more effectively than CPT-11 alone. These results
      demonstrate that the combination of edaravone with CPT-11 may constitute a new
      strategy for treating primary and metastatic colon cancer.

PMID- 16095812
TI  - YM-201627: an orally active antitumor agent with selective inhibition of vascular
      endothelial cell proliferation.
AB  - We developed an oral administration-compatible, small molecular weight antitumor
      agent, YM-201627 by screening for the inhibition of the proliferation of VEGF
      stimulated HUVECs. YM-201627 selectively inhibited the proliferation of various
      endothelial cell lines induced by VEGF, bFGF, and FBS (at IC50s of 0.0039-0.12
      microM), that would not be expected to have any direct antiproliferative effect
      on other cell types. YM-201627 inhibited angiogenesis in vitro at a concentration
      of 0.01 microM. In the in vivo studies, it inhibited microvessel formation
      induced by human melanoma A375 cells suspended in Matrigel (86% with twice-daily
      doses of 30 mg/kg). Moreover, once-daily oral dosing of YM-201627 to mice bearing
      A375 xenografts elicited significant antitumor activity (73% with daily doses of
      10 mg/kg). These results suggest that YM-201627 is a selective growth inhibitor
      of endothelial cells, which may be useful for treatment of solid tumors.

PMID- 16095813
TI  - Effects of iron surface pretreatment on kinetics of aqueous nitrate reduction.
AB  - Using hydrogen gas at 400 degrees C to activate iron surface was proposed to
      remove nitrate (40 mg NL(-1)) in a HEPES buffer solution at pH value between 6.5
      and 7.5. Compared with the nonpretreated iron, the first-order reaction rate
      constant (kobs) was increased 4.7 times by pretreated iron, and the lag of the
      early period disappeared. Normalized to iron surface area concentration, the
      specific rate constant (kSA) was increased approximately by a factor of 6 using
      hydrogen reduction (0.0020 min(-1)m(-2)L for nonpretreated iron and 0.0128 min(
      1)m(-2)L for pretreated iron). The reactivity of aged iron covered by a complex
      mixture of iron oxides (soaking in nitrate solution for 60 days) were restored by
      hydrogen gas at 400 degrees C. Scanning electron microscopy (SEM) and temperature
      programmed reduction (TPR) exhibited visibly cleaner without pitting and cracking
      and less oxygen fraction on pretreated iron surface relative to nonpretreated
      iron. Activation energies (Ea) of nitrate reduction over the temperature range of
      10-45 degrees C were 46.0 kJ mol(-1) for nonpretreated iron, and 32.0 kJ mol(-1)
      for pretreated iron, indicating chemical reaction control, rather than diffusion.
      The results indicated that this enhancement was attributed to the increase in
      active site concentration on iron surface by hydrogen reduction.

PMID- 16095814
TI  - Semiconductor-mediated photocatalysed degradation of two selected azo dye
      derivatives, amaranth and bismarck brown in aqueous suspension.
AB  - Semiconductor-mediated photocatalysed degradation of two selected azo dye
      derivatives such as amaranth (1) and bismarck brown (2) has been investigated in
      aqueous suspension by monitoring the change in substrate concentration employing
      UV spectroscopic analysis technique as a function of irradiation time. The
      degradation was studied under different conditions such as types of TiO(2), pH,
      substrate concentration, catalyst concentration, and in the presence of electron
      acceptors such as hydrogen peroxide (H(2)O(2)), potassium bromate (KBrO(3)) and
      ammonium persulphate (NH(4))(2)S(2)O(8) besides air. The degradation rates were
      found to be strongly influenced by all the above parameters. The photocatalyst
      Degussa P25 showed comparatively highest photocatalytic activity. The dye
      derivative, bismarck brown (2) was found to degrade faster than amaranth dye (1).

PMID- 16095815
TI  - NGF-induced phosphatidylinositol 3-kinase signaling pathway prevents thapsigargin
      triggered ER stress-mediated apoptosis in PC12 cells.
AB  - Tunicamycin, an inhibitor of the glycosylation of newly biosynthesized proteins,
      induces endoplasmic reticulum (ER) stress and subsequent apoptosis, and caspase
      family proteases are activated during the process of ER stress-mediated
      apoptosis. In the present study, we showed that thapsigargin (Th), an inhibitor
      of the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA), also induced ER
      stress-mediated apoptosis, and nerve growth factor (NGF) prevented the apoptosis
      in PC12 cells. We also found that LY 294002, an inhibitor of phosphatidylinositol
      3-kinase (PI 3-K), reduced the survival of cells treated with NGF for 24h in the
      presence of Th. We discovered that the activities of caspase-3, -9 and -12 were
      increased time-dependently after the treatment with Th, and NGF suppressed the Th
      triggered activation of caspase-3, -9 and -12. LY 294002 diminished the effect of
      NGF on the inactivation of all these caspases. These results indicate that the
      NGF-induced PI 3-K signaling pathway prevents Th-triggered ER stress-specific
      apoptosis via inhibition of caspase-mediated apoptotic signal.

PMID- 16095816
TI  - Stimulatory effect of morphine on rat pineal melatonin synthesis via a cyclic AMP
      dependent transcription pathway.
AB  - The expression of mRNA of opioid receptors and the existence of opioid binding
      site in the rat pineal gland have been demonstrated previously. A major finding
      was that morphine enhanced the activity of the rate-limiting enzyme, N
      acetyltransferase (NAT) and increased the level of melatonin in rat pineal gland.
      An attempt has been made in order to clarify the mechanism of this induction. In
      the present study, the stimulatory effect of morphine on the expression of NAT
      mRNA in the rat pineal gland has been demonstrated using semi-quantitative RT-PCR
      technique. The results showed that both acute and chronic morphine treatments
      significantly increased NAT mRNA expression in rat pineal gland. In addition, the
      effect of morphine on the phosphorylation of the transcription factors, cyclic
      AMP responsive element-binding protein (CREB) was investigated. Western blot
      analysis showed that morphine significantly increased phosphorylation of CREB.
      These results indicate that at least one downstream messenger pathway for the
      activation of opioidergic system on the induction of melatonin synthesis in the
      rat pineal gland acts via cyclic AMP-dependent cascade and transcription
      mechanism.

PMID- 16095817
TI  - Increased susceptibility to oxidative stress in scrapie-infected neuroblastoma
      cells is associated with intracellular iron status.
AB  - The molecular mechanism of neurodegeneration in prion diseases remains largely
      uncertain, but one of the features of infected cells is higher sensitivity to
      induced oxidative stress. In this study, we have investigated the role of iron in
      hydrogen peroxide (H(2)O(2))-induced toxicity in scrapie-infected mouse
      neuroblastoma N2a (ScN 2 a) cells. ScN 2 a cells were significantly more
      susceptible to H(2)O(2) toxicity than N2a cells as revealed by cell viability
      (MTT) assay. After 2h exposure, significant decrease in cell viability in ScN 2 a
      cells was observed at low concentrations of extracellular H(2)O(2) (5-10 microM),
      whereas N2a cells were not affected. The increased H(2)O(2) toxicity in ScN 2 a
      cells may be related to intracellular iron status since ferrous iron (Fe(2+))
      chelator 2,2'-bipyridyl (BIP) prevented H(2)O(2)-induced decrease in cell
      viability. Further, the level of calcein-sensitive labile iron pool (LIP) was
      significantly increased in ScN 2 a cells after H(2)O(2) treatment. Finally, the
      production of reactive oxygen species (ROS) was inhibited by 30% by iron
      chelators desferrioxamine (DFO) and BIP in ScN 2 a cells, whereas no significant
      effect of iron chelators on basal ROS production was observed in N2a cells. This
      study indicates that cellular resistance to oxidative stress in ScN 2 a cells is
      associated with intracellular status of reactive iron.

PMID- 16095818
TI  - DNA sequence variations in the prolyl isomerase Pin1 gene and Alzheimer's
      disease.
AB  - Senile plaques and neurofibrillary tangles (NFT) are the prominent lesions in the
      brain of Alzheimer's disease (AD) patients. NFT are mainly composed of an
      abnormally phosphorylated form of tau protein, which has lost its function to
      bind microtubules and promote their assembly. Tau hyperphosphorylation critically
      decreases tau function and precedes neurodegeneration. The majority of tau
      phosphorylation sites are Ser/Thr-Pro motifs, which are known to exist in two
      distinct cis and trans conformations. The prolyl isomerase Pin1 catalyses the
      conversion of those conformations. Pin1 binds to tau specifically at the Thr231
      Pro site and restores tau function, either by inducing conformational changes or
      facilitating dephosphorylation. It has been shown that Pin1 expression levels
      inversely correlate with the predicted vulnerability of different brain areas to
      neurodegeneration and soluble Pin1 is depleted in neurons from AD brains;
      furthermore, Pin1 knock-out mice develop signs and symptoms of tau-related
      pathologies late in life. It seems that Pin1 plays an important role in
      maintaining tau function, thereby preserving neuronal homeostasis and preventing
      age-dependent neurodegeneration. DNA sequence variations in Pin1 gene may affect
      its expression level or function and influence the individual risk for developing
      AD. We screened by denaturing high performance liquid chromatography the genomic
      DNA of 120 AD subjects and 134 age-matched controls and we found very few and
      rare sequence variations in the promoter region and in exons 2 and 3. We conclude
      that Pin1 is a very well conserved gene, whose rare nucleotide variations have no
      effect on the individual genetic risk for AD.

PMID- 16095819
TI  - Buspirone attenuates conditioned fear-induced c-Fos expression in the rat
      hippocampus.
AB  - The role of hippocampus in the anxiolytic-like effect of buspirone in the
      conditioned emotional response test (CER, a freezing response), was examined by
      immunocytochemical detection of the c-Fos protein. It was shown that buspirone at
      the dose of 0.5 and 1.5 mg/kg i.p. given before test session, which was 24 h
      after the aversive training, significantly decreased freezing response within a
      limited dose range of the U-shaped dose-response relationship. Exposure of
      animals to aversively conditioned context (a contextual fear) induced the
      production of c-Fos protein in the dentate gyrus, CA-1 and CA-3 layers of the
      hippocampus. Pretreatment with buspirone (1.5 mg/kg) significantly attenuated the
      effects of aversive memory on c-Fos protein expression in the CA-1 and CA-3
      layers of the hippocampus. These immunocytochemical results support previous data
      obtained in our laboratory with the help of selective neurotoxic lesions and
      intrahippocampal drug injections suggesting an important role of hippocampus in
      the anxiolytic effects of buspirone.

PMID- 16095820
TI  - Nicotinic receptor involvement in antinociception induced by exposure to
      cigarette smoke.
AB  - Direct exposure of rats to tobacco smoke induces antinociception. We presently
      investigated if this antinociception is mediated via nicotinic and/or mu-opioid
      receptors. Adult male rats were surgically implanted with Alzet osmotic minipumps
      that delivered either saline (control), the nicotinic antagonist mecamylamine, or
      the opiate antagonist naltrexone (3 mg/kg/day i.v. for 21 days). Nocifensive
      responses were assessed on alternate days using tail-flick reflex latency (TFL)
      over a 3-week period. During the second week, the rats were exposed to
      concentrated cigarette smoke in an environmental chamber for 6 h/day for 5
      consecutive days; a control group was similarly exposed to filtered cigarette
      smoke. Rats receiving mecamylamine and naltrexone exhibited a significant weight
      loss after the first day of infusion. All treatment groups additionally exhibited
      significant weight loss during exposure to unfiltered or filtered smoke. The
      saline group exhibited significant antinociception on the first day of smoke
      exposure with rapid development of tolerance. The mecamylamine and naltrexone
      groups did not exhibit significant antinociception. Controls exposed to filtered
      smoke (with approximately 50% lower nicotine concentration) also exhibited
      significant analgesia on the first exposure day with rapid development of
      tolerance. Exposure to high levels of cigarette smoke, or to filtered smoke with
      a lower nicotine concentration in the vapor phase, induces antinociception with
      rapid development of tolerance. The antinociceptive effect appears to be mediated
      via nicotinic and mu-opioid receptors.

PMID- 16095821
TI  - Timing and distance characteristics of interpersonal coordination during
      locomotion.
AB  - Most studies about human locomotion only tend to consider single subjects walking
      alone in a stationary environment. Nevertheless, human subjects have often to
      plan and generate their locomotor trajectories according to one another's
      displacements. Therefore, in the present study we address the question of the
      interpersonal coordination when pairs of subjects walk simultaneously. Six pairs
      of subjects walking face to face, backwards and forwards on a 8 m x 2 m track
      were involved in our experiment. Within each pair, the leader (L) was required to
      break the initial interpersonal distance whereas the follower (F) had to maintain
      this distance constant (1, 2 or 3 m). We measured their position and analyzed
      their travelled distance, the time course of their linear displacement, and the
      kinematics parameters of their steps. Our results show that F travels smaller
      distances than L and that even if they are highly correlated, some temporal
      delays exist between displacements of L and F with greater values when the
      interpersonal distance increases (from 1 to 3 m). These results are discussed in
      terms of high level imitation, i.e. bidirectional interactions with mutual
      influences of each subject on one another.

PMID- 16095822
TI  - Pharmacological interactions between calcium/calmodulin-dependent kinase II alpha
      and TRPV1 receptors in rat trigeminal sensory neurons.
AB  - Multiple lines of evidence suggest that calcium/calmodulin-dependent kinase II
      alpha (CaMKIIalpha) plays an important role in the spinal dorsal horn in
      nociceptive models of chemical, inflammatory and nerve injury. Moreover,
      CaMKIIalpha phosphorylates the vanilloid receptor type 1 (TRPV1), thereby
      regulating vanilloid agonist binding to the receptor. Herein, we have explored a
      possible interaction of CaMKIIalpha activity with the TRPV1 receptor in rat
      trigeminal ganglion (TG) neurons in vitro. Inhibition of CaMKIIalpha with KN-93
      (5 microM) inhibited capsaicin (CAP)- and n-arachidonoyl-dopamine (NADA)-evoked
      calcitonin gene-related peptide (CGRP) release effectively decreasing the Emax
      for both compounds. This effect was not mimicked by the inactive compound KN-92
      (5 microM), indicating that the effect was mediated by CaMKIIalpha inhibition.
      CAP also stimulated a significant approximately 50% increase in
      autophosphorylation of CaMKIIalpha at Thr286/287. Immunocytochemistry for phospho
      CaMKIIalpha indicated that this effect specifically occurred in TRPV1-positive TG
      neurons. These findings indicate that phopho-CaMKIIalpha is likely to play a role
      in presynaptic primary afferents in animal models of nociceptive hypersensitivity
      and provide support for CaMKIIalpha modulation of TRPV1 activity in sensory
      neurons.

PMID- 16095823
TI  - Differential effect of PMS777, a new type of acetylcholinesterase inhibitor, and
      galanthamine on oxidative injury induced in human neuroblastoma SK-N-SH cells.
AB  - In the search for highly selective and potent cholinesterase inhibitors (AChEI)
      being able to improve oxidative injury, PMS777, a tetrahydrofuran derivative, was
      designed as a novel dual PAF and acetylcholinesterase inhibitor. The aim of this
      study was to investigate the modulatory effects of PMS777 and galanthamine,
      another AChEI, on the oxidative injury induced in neuronal cells. The SK-N-SH
      cells stimulated with LPS+IL-(1beta) were selected to investigate the direct
      inhibitory effect of PMS777 and galanthamine. LPS+IL-(1beta) induced oxidative
      injury as assessed by ROS production (29%), GSH depletion (11%) and loss of
      mitochondrial activity (22%). GSH depletion was never decreased by either drug.
      In contrast, ROS production and mitochondrial activity were totally prevented by
      addition of PMS777 but not galanthamine. PMS777 also inhibits butylcholinesterase
      and it shows selectivity for acetylcholinesterase. Thus, this PAF antagonist
      inaugurates a new type of AChEI, able to fight oxidative injury. Therefore,
      PMS777 could be of interest on patients with cognitive impairments and
      inflammatory damage, as in AD.

PMID- 16095826
TI  - Nanotribological characterization of human hair and skin using atomic force
      microscopy.
AB  - Healthy hair and skin is highly desired. Characterization of their morphological,
      frictional, and adhesive properties (tribological properties) is essential to
      enhance understanding of hair and skin and to advance the science. Literature on
      the tribological characterization of hair and skin is scarce to date. The paper
      presents nanotribological data and analysis on hair (Caucasian, Asian, and
      African hair at virgin, chemo-mechanically damaged, and treated conditions) and
      synthetic hair and skin, as well as roughness data of human skin replica.
      Roughness statistics are presented to characterize the vertical and spatial
      surface parameters. Average coefficient of friction values were determined for
      each ethnicity and hair type, and are discussed. The directionality dependence of
      friction is also discussed. Magnitude and spatial distribution of adhesive force
      are used to estimate thickness and distribution of the conditioner film.

PMID- 16095837
TI  - Study of fibrinogen adsorption on self-assembled monolayers on Au(111) by atomic
      force microscopy.
AB  - The adsorption of plasma protein fibrinogen on the self-assembled monolayers
      (SAMs) of n-hexadecyl mercaptan and citrate was investigated with atomic force
      microscopy (AFM). On the basis of the preparation of these two flat SAMs on
      Au(111), high-resolution AFM images of bovine fibrinogen were obtained with
      different protein concentrations. The results indicated that the surface chemical
      composition significantly affected the adsorption behavior of fibrinogen. Since
      fibrinogen plays a key role in the regulation of both haemostasis and thrombosis,
      high-resolution AFM imaging on SAMs is expected to be an effective approach to
      study the haemocompatibility of materials with different surface chemistry.

PMID- 16095840
TI  - A decade of discoveries in veterinary protozoology changes our concept of
      "subclinical" toxoplasmosis.
AB  - One of the most compelling topics to emerge from the last decade of veterinary
      protozoology is disease caused by a zoonotic pathogen, Toxoplasma gondii, in
      otherwise healthy people. These findings may catch the health professions by
      surprise, because veterinary and medical courses and textbooks typically
      emphasize that T. gondii infections are subclinical, unless acquired in utero or
      the patient has a serious immunosuppressive condition. Nevertheless, numerous
      reports in the last decade associate toxoplasmosis with lymphadenopathy, fever,
      weakness and debilitation, ophthalmitis, and severe multisystemic infections in
      people who do not have immunosuppressive conditions. Toxoplasmosis in rodents
      causes altered behavior, and similar mental aberrations are coming to light in
      humans; recent studies associate T. gondii infection with personality shifts and
      increased likelihood of reduced intelligence or schizophrenia. These conditions
      reduce the quality of life of individuals, and may exact a significant economic
      burden upon society. Of course, toxoplasmosis continues to cause serious
      conditions in AIDS patients and congenitally infected people, as well as
      abortions and encephalitis in domestic and wild animals. Environmental
      contamination is heavy enough to extend into marine wildlife. It is time for the
      health professions to amend teaching curricula regarding T. gondii. Veterinary
      parasitologists should lead the way in developing methods to reduce the
      prevalence of T. gondii in food animals. Public health policies should prohibit
      the practice of allowing pet cats to roam. Organizations and individuals that
      feed feral cats are unwittingly contributing to the dissemination of T. gondii,
      by sustaining artificially dense populations of a definitive host of this
      protozoal parasite.

PMID- 16095841
TI  - Vaccines against veterinary helminths.
AB  - The majority of attempts to develop commercial vaccines for veterinary helminths
      have focussed on identifying protein antigens, which could be formulated as
      protective vaccines. Notable successes have been achieved for some cestode
      parasites, where recombinant proteins have been developed into highly effective
      vaccines. Although effective protection can also be obtained using some nematode
      proteins in their native forms, it has not yet been possible to formulate
      commercially successful vaccines for other helminth parasites of veterinary
      significance. Increasing evidence suggests that parasite glycan moieties may
      provide an alternative source of vaccine antigens, and increased attention is now
      being given to this class of compounds. In addition to identifying candidate
      protective antigen(s), an increased research effort is needed to develop
      appropriate strategies for the formulation and delivery of helminth vaccines.

PMID- 16095843
TI  - Alcohol expectancies and current mood state in social drinkers.
AB  - BACKGROUND: Whereas the relationship between affective states and drinking
      behaviour is well established, there is only limited evidence to support the
      notion that an individual's current mood state is related to his or her alcohol
      expectancies. Moreover, previous research focused predominantly on the impact of
      affective valence and, at the same time, failed to assess an individual's
      evaluation of alcohol effects. METHOD: Three hundred and fifty-seven volunteers
      completed a German-language version of the Anticipated Biphasic Alcohol Effects
      Scale (ABAES), a mood form, and a brief questionnaire on background variables and
      drinking habits. Furthermore, participants were asked to evaluate each alcohol
      effect described in the ABAES. RESULTS: Those participants feeling tired and worn
      out anticipated higher levels of alcohol-induced sedation. Positive affect was
      related to a more negative evaluation of alcohol-induced sedation. The assessment
      of outcome value revealed remarkable individual differences in the evaluation of
      alcohol's stimulating effects. CONCLUSIONS: The present findings suggest that
      current mood state may determine drinking behaviour by altering both the strength
      of outcome expectancies and the evaluation of alcohol's effects. Future research
      may establish the relationship between current mood state and alcohol-related
      cognitions in clinical samples.

PMID- 16095844
TI  - Self-efficacy as a predictor of treatment outcome in adolescent substance use
      disorders.
AB  - Youth substance abuse relapse prevention was examined as a function of patients'
      situational self-efficacy (SE), their confidence to abstain from substance use in
      high-risk situations. An increase in SE has been shown to be enhanced by
      cognitive behavioral therapy (CBT) in adults. Eighty-eight adolescent substance
      abusers were randomly assigned to either CBT or psycho-education (PET) group
      therapy. Substance use and SE were assessed at end of treatment, 3- and 9-months
      after the end of planned treatment. Increased SE predicted subsequent abstinence
      independently from drug urinalysis and treatment condition only during treatment,
      while previous substance use predicted subsequent self-efficacy. CBT was not
      differentially effective than PET in promoting SE. It is recommended that
      potential mediators and moderators of SE in the treatment of adolescent substance
      abuse should be further explored.

PMID- 16095845
TI  - Adolescent alcohol use disorders predict adult borderline personality.
AB  - BACKGROUND: This study investigated adolescent alcohol use disorders (AUDs) and
      other characteristics as predictors of adult borderline personality disorder
      (BPD) symptoms. METHODS: Adolescents with AUDs (n = 355) were recruited from
      clinical treatment sources and adolescents without AUDs (n = 169) were recruited
      from the community. During an adolescent assessment (age 16+/-1.3), childhood
      physical and/or sexual abuse history, AUDs and associated psychiatric disorders
      were measured via semi-structured interviews. Symptoms of BPD were measured in a
      young adult follow-up assessment (age 22+/-2.4). Latent class analysis was
      utilized to classify individuals into four categories based upon BPD symptom
      profiles. RESULTS: Multinomial regression models indicated that adolescent AUDs
      and other psychiatric disorders mediated the relationship between child physical
      and/or sexual abuse and adult BPD latent class. CONCLUSIONS: Results were
      consistent with a developmental conceptualization of BPD, with AUDs and other
      adolescent psychopathology antecedents representing developmentally relevant
      forms of dysregulation, and in their more severe forms culminating in borderline
      symptomatology.

PMID- 16095846
TI  - Probiotic lactobacilli: an innovative tool to correct the malabsorption syndrome
      of vegetarians?
AB  - Vegetarians may have subtle nutritional deficiencies which have been related to
      the occurrence of an unrecognized malabsorption syndrome. The excess phytate
      content in cereals, nuts, legumes and oilseeds which represent the mainstay of
      their food intake, seems to play a central role in the pathogenesis of this
      malabsorption syndrome as an inverse relationship has been shown to link the
      phytate content of the diet with the intestinal absorption of trace minerals and
      proteins. We postulate that manipulating the endogenous digestive microflora of
      subjects on a vegetarian diet through administering probiotic lactic bacteria
      would represent an innovative tool to counteract the occurrence of the
      malabsorption syndrome dependent on the high phytate content of their diet. Even
      though there are no data about the composition of endogenous digestive microflora
      in subjects on a vegetarian diet, we expect that probiotic lactobacilli can
      interact with or affect distinct yet interrelated components within the
      intestinal milieu, such as epithelial cells, enteric flora, and/or mucosal immune
      cells. This would ultimately translate into the correction of the unregulated
      mechanisms implicated in the altered intestinal absorption of trace metals and
      proteins commonly seen in vegetarians. Clinical experience with probiotic therapy
      of patients with inflammatory bowel disease fully agrees with this view. One
      additional point of interest is that probiotic lactobacilli, and other species of
      the endogenous digestive microflora as well, are an important source of the
      enzyme phytase which catalyses the release of phosphate from phytate and
      hydrolyses the complexes formed by phytate and metal ions or other cations,
      rendering them more soluble ultimately improving and facilitating their
      intestinal absorption. The regular intake of probiotic preparation, may represent
      a cheap and safe tool in order to convert a diet with a low potential for
      bioavailability of trace minerals and proteins, such as the vegetarian diet, into
      a diet with a high bioavailability potential. The benefit of such an approach
      would not be restricted to vegetarians.

PMID- 16095847
TI  - Radical radiotherapy for early glottic cancer: Results in a series of 1087
      patients from two Italian radiation oncology centers. I. The case of T1N0
      disease.
AB  - PURPOSE: To retrospectively evaluate local control rates, late damage incidence,
      functional results, and second tumor occurrence according to the different
      patient, tumor, and treatment features in a large bi-institutional series of T1
      glottic cancer. METHODS AND MATERIALS: A total of 831 T1 glottic cancer cases
      treated consecutively with radical intent at the Florence University Radiation
      Oncology Department (FLO) and at the Radiation Oncology Department of the
      University of Brescia-Istituto del Radio "O. Alberti" (BS) were studied.
      Actuarial cumulative local control probability (LC), disease-specific (DSS), and
      overall survival (OS) rates have been calculated and compared in the different
      clinical and therapeutic subgroups with both univariate and multivariate
      analysis. Types of relapse and their surgical salvage have been evaluated, along
      with the functional results of treatment. Late damage incidence and second tumor
      cumulative probability (STP) have been also calculated. RESULTS: In the entire
      series, 3-, 5-, and 10-year OS was equal to 86%, 77%, and 57%, respectively.
      Corresponding values for LC were 86%, 84%, and 83% and for DSS 96%, 95%, and 93%,
      taking into account surgical salvage of relapsed cases. Eighty-seven percent of
      the patients were cured with function preserved. Main determinants of a worse LC
      at univariate analysis were: male gender, earlier treatment period, larger tumor
      extent, anterior commissure involvement, and the use of Cobalt 60. At
      multivariate analysis, only gender, tumor extent, anterior commissure
      involvement, and beam type retained statistical significance. Higher total doses
      and larger field sizes are significantly related (logistic regression) with a
      higher late damage incidence. Scatterplot analysis of various combinations of
      field dimensions and total dose showed that field dimensions >35 and <49 cm2,
      together with doses of >65 Gy, offer the best local control results together with
      an acceptably low late damage incidence. Twenty-year STP was equal to 23%, with
      second tumor deaths being more frequent than larynx cancer deaths (67 of 831 vs.
      46/831). CONCLUSION: The results of this study support the opinion, suggested by
      some international guidelines, that radiotherapy is standard treatment for T1
      glottic cancer. Better results are obtained in patients with less extended
      disease and with 4-6 MV photon beams. The use of doses in excess of 65 Gy and of
      field sizes of 36-49 cm2 is probably the best technical choice available. Late
      damage is infrequent, but careful follow-up is warranted to detect early not only
      relapses (because conservative salvage surgery is feasible), but also second
      malignant tumors, which constitute the main cause of death in these patients and
      are potentially curable.

PMID- 16095848
TI  - Evaluating the influence of setup uncertainties on treatment planning for focal
      liver tumors.
AB  - PURPOSE: A mechanism has been developed to evaluate the influence of random setup
      variations on dose during treatment planning. The information available for
      studying these factors shifts from population-based models toward patient
      specific data as treatment progresses and setup measurements for an individual
      patient become available. This study evaluates the influence of population as
      well as patient-specific setup distributions on treatment plans for focal liver
      tumors. METHODS AND MATERIALS: Eight patients with focal liver tumors were
      treated on a protocol that involved online setup measurement and adjustment, as
      well as ventilatory immobilization. Summary statistics from these three
      dimensional conformal treatments yielded individual and population distributions
      of position at initial setup for each fraction. A convolution model for
      evaluation of the influence of random setup variation on calculated dose
      distributions has been previously described and investigated for application to
      focal liver radiotherapy by our department. Individual patient doses based on
      initial setup positions were calculated by convolving the calculated dose
      distribution with an anisotropic probability distribution function representing
      the individual patient's random variations. A separate convolution using
      population-averaged random variations was performed. Individual beam apertures
      were then adjusted to provide plans that ensured proper dose to the clinical
      target volume following convolution with population distributions, as well as
      individual patient position uncertainty models. RESULTS: Individual patient setup
      distributions for the course of treatment had random setup variations (sigma)
      that ranged from 2.5 to 5.7 mm (left-right), 2.1 to 8.3 mm (anterior-posterior),
      and 4.1 to 10.8 mm (cranial-caudal). The population random components were 4.2 mm
      (left-right), 4.1 mm (anterior-posterior), and 7.0 mm (cranial-caudal) at initial
      setup. The initial static planned dose distribution overestimated the volume of
      liver irradiated to high doses, because inclusion of setup uncertainties
      generally blurred the resulting doses, shifting the higher-dose region of normal
      liver dose-volume histograms to lower doses. Furthermore, the population-based
      dose convolution tended to predict a higher risk of radiation damage to the liver
      (based on an in-house parameterization of the Lyman normal tissue complication
      probability model) than the individual patient calculations. For an individual
      plan, application of different individual random variations yielded change in
      effective volume differences with a 3% range. Plan adjustment to account for
      random setup variations generally resulted in a lower change in effective volume
      than initial planning using a planning target volume followed by calculation of
      delivered dose based on random offsets. CONCLUSION: This study hints at the
      factors that most strongly influence planning of liver treatments taking into
      account geometric variations. Given a setup verification methodology that rapidly
      reduces systematic offsets, the importance of realistic incorporation of
      geometric variations as an initial step in treatment planning, as well as
      possible plan refinement, is demonstrated.

PMID- 16095849
TI  - High-dose radioiodine treatment for differentiated thyroid carcinoma is not
      associated with change in female fertility or any genetic risk to the offspring.
AB  - BACKGROUND: We tried to evaluate the female fertility and genetic risk to the
      offspring from the exposure to high-dose (131)I by assessing the pregnancy
      outcomes and health status of the children of female patients with differentiated
      thyroid cancer who had received therapeutic doses of (131)I. MATERIALS AND
      METHODS: From 1967 to 2002, a total of 1,282 women had been treated with (131)I.
      Of these patients, 692 (54%) were in the reproductive age group (18-45 years).
      Forty women had a total of 50 pregnancies after high-dose (131)I. Age at
      presentation ranged from 16 to 36 years (mean, 23 +/- 4 years). Histopathology
      was papillary thyroid cancer in 32 cases and follicular thyroid cancer in 8
      cases. RESULTS: Single high-dose therapy was given in 30 cases, 2 doses were
      given in 7 cases, 3 doses were given in 2 cases, and four doses were given in 1
      case in which lung metastases had occurred. In 37 patients (92%), disease was
      successfully ablated before pregnancy. Ovarian absorbed-radiation dose calculated
      by the MIRD method ranged from 3.5 to 60 cGy (mean, 12 +/- 11 cGy). The interval
      between (131)I therapy and pregnancy varied from 7 to 120 months (37.4 +/- 28.2
      months). Three spontaneous abortions occurred in 2 women. Forty-seven babies (20
      females and 27 males) were born. Forty-four babies were healthy with normal birth
      weight and normal developmental milestones. Twenty women delivered their first
      baby after (131)I therapy. The youngest child in our series is 11 months of age,
      and the oldest is 8.5 years of age. CONCLUSIONS: Female fertility is not affected
      by high-dose radioiodine treatment, and the therapy does not appear to be
      associated with any genetic risks to the offspring.

PMID- 16095850
TI  - Effect of training delays and start and stop markers on the choose-short effect
      in pigeons.
AB  - Pigeons were trained in a matching-to-duration task using short and long filled
      intervals. Group 2/8 was trained with 2- and 8-s intervals, Group 4/10 with 4-
      and 10-s intervals, and group marker with 2- and 8-s intervals presented between
      1-s start and stop markers. Extended-delay testing showed no significant choose
      short effect (CSE) in any group. It was hypothesized that the lack of a CSE may
      have resulted from use of a variable delay (range 1-3s) during training. The same
      subjects were employed in Experiment 2 and were trained with a new set of
      comparisons and one of the alternate types of samples employed in Experiment 1.
      All training trials involved a 0-s delay. Extended-delay testing revealed a
      significant CSE in Groups 2/8 and 4/10 but only a weak, and statistically
      nonsignificant, CSE in group marker. It was concluded that use of a variable
      delay during training reduced the CSE. The notion that subjective shortening
      underlies the CSE provided an adequate account of these findings.

PMID- 16095851
TI  - Timing, memory for intervals, and memory for untimed stimuli: the role of
      instructional ambiguity.
AB  - Theories of animal timing have had to account for findings that the memory for
      the duration of a timed interval appears to be dramatically shorted within a
      short time of its termination. This finding has led to the subjective shortening
      hypothesis and it has been proposed to account for the poor memory that animals
      appear to have for the initial portion of a timed interval when a gap is inserted
      in the to-be-timed signal. It has also been proposed to account for the poor
      memory for a relatively long interval that has been discriminated from a shorter
      interval. I suggest here a simpler account in which ambiguity between the gap or
      retention interval and the intertrial interval results in resetting the clock,
      rather than forgetting the interval. The ambiguity hypothesis, together with a
      signal salience mechanism that determines how quickly the clock is reset at the
      start of the intertrial interval can account for the results of the reported
      timing experiments that have used the peak procedure. Furthermore, instructional
      ambiguity rather than memory loss may account for the results of many animal
      memory experiments that do not involve memory for time.

PMID- 16095852
TI  - A consistent attentional bias for drug-related material in active cocaine users
      across word and picture versions of the emotional Stroop task.
AB  - Evidence from a number of drug-abuse populations suggests that an attentional
      bias for drug-related stimuli can be identified in chronic users. Such an effect
      has yet to be reliably demonstrated in cocaine users, despite mounting evidence
      of the salience and reinforcing properties of cocaine-related cues. The aim of
      the current study was to administer word (modeled on the versions shown to
      successfully identify attentional biases in alcohol abusers) and picture versions
      of the emotional Stroop tasks to gauge the reliability of cocaine-specific
      attentional biases across stimuli domains. A comparison of active cocaine users
      (n = 23), and their age and education matched controls revealed a significant
      bias for cocaine-related pictures and words in users. This attentional bias could
      not be attributed to confounding factors such as slowed response speed of cocaine
      users, cocaine-related material sharing category ownership, or that the cocaine
      related material used in the current study was generally arousing for all
      participants. A comparison of the different classes of stimuli indicated that
      cocaine users had a very similar level of difficulty controlling their attention
      towards both cocaine-related material and incongruent-colour word stimuli, the
      latter being the traditional measure of attentional control from the Stroop task.
      These results provide corroborating evidence for cognitive biases being a
      hallmark of substance dependence.

PMID- 16095853
TI  - Euonymus alatus prevents the hyperglycemia and hyperlipidemia induced by high-fat
      diet in ICR mice.
AB  - Euonymus alatus (EA), known as a Gui Jeon Wu in China, has been used as a folk
      medicine for regulating blood circulation, relieving pain, eliminating blood
      clot, and treating dysmenorrhea in Asian countries. Although EA has anecdotally
      ascertained to show the anti-hyperglycemic activity by enhancing insulin
      secretion, there is no sufficient experimental evidence for anti-hyperglycemic
      activity of EA. The purpose of this study was to investigate the preventive
      effect of 50% ethanol extract of EA in high-fat diet-induced hyperglycemic and
      hyperlipidemic ICR mice. At 6 week old, the ICR mice were randomly divided into
      five groups; two control and three treatment groups. The control mice was to
      receive either a regular diet (RD) or high-fat diet (HFD), and the treatment
      groups were fed a high-fat diet with either 350, 700 mg/kg of EA (EA350 and
      EA700) or 250 mg/kg of metformin (MET250) for a 10-week period. EA not only
      reduced body weight in a dose dependent manner, but also corrected associated
      hyperinsulinemia and hyperlipidemia. EA exerted beneficial effects on glucose and
      lipid homeostasis in diabetes that are not secondary to its ability to decrease
      food intake but its specific effects on hepatic lipogenesis related genes
      (SREBPla, FAS, GAPT) and PPAR-gamma gene expression in periepididymal fat. Taken
      together, the combined effect of EA to reduce plasma glucose and lipid levels,
      and reduce the deposition of triglyceride in the liver are indicative of a marked
      improvement in obesity-related diabetes and non-alcoholic fatty liver disease.

PMID- 16095854
TI  - Anticonvulsant and neurotoxicity profile of Nardostachys jatamansi in rats.
AB  - Ethanol extract of the roots of Nardostachys jatamansi DC. (Valerianaceae) was
      studied for its anticonvulsant activity and neurotoxicity, alone and in
      combination with phenytoin in rats. The results demonstrated a significant
      increase in the seizure threshold by Nardostachys jatamansi root extract against
      maximal electroshock seizure (MES) model as indicated by a decrease in the
      extension/flexion (E/F) ratio. However, the extract was ineffective against
      pentylenetetrazole (PTZ)-induced seizures. Nardostachys jatamansi root extract
      also showed minimal neurotoxicity against rotarod test at doses that increased
      the seizure threshold. Further, pretreatment of rats with phenytoin at a dose of
      12.5, 25, 50 and 75 mg/kg in combination with 50mg/kg of Nardostachys jatamansi
      root extract resulted in a significant increase in the protective index (PI) of
      phenytoin from 3.63 to 13.18. The dose response studies of phenytoin alone and in
      combination with Nardostachys jatamansi extract on the serum levels of phenytoin
      clearly demonstrated the synergistic action of both the drugs.

PMID- 16095855
TI  - Immunosuppressive activity of Pollen Typhae ethanol extract on the immune
      responses in mice.
AB  - The immunosuppressive activity of the ethanol extract of Pollen Typhae (EEPT)
      consisting of a mixture of flavonoids, steroids and volatile oils was studied on
      the immune responses in mice. EEPT significantly suppressed concanavalin A (Con
      A)- and lipopolysaccharide (LPS)-stimulated splenocyte proliferation in vitro in
      a concentration-dependent manner. ICR mice were immunized subcutaneously with OVA
      on days 0 and 14. Beginning on the day of immunization, the mice were
      administered intraperitoneally with EEPT at a single dose of 0.25, 0.5, and 1.0
      mg at intervals of 7 days for a total of five doses. On day 28, antigen-specific
      antibodies in serum, and mitogen- and OVA-induced splenocyte proliferation were
      measured. EEPT significantly suppressed Con A-, LPS- and OVA-induced splenocyte
      proliferation in the OVA-immunized mice in a dose-dependent manner. Moreover, the
      OVA-specific total IgG, IgG1 and IgG2b levels in the OVA-immunized mice were
      significantly reduced by EEPT. The results suggest that EEPT could suppress the
      cellular and humoral response in mice, and deserve further researches to be
      developed as immunosuppressant.

PMID- 16095856
TI  - Laryngeal findings and voice quality in Sjogren's syndrome.
AB  - OBJECTIVE: The effect of Sjogren syndrome (SS) on perceptual ratings of the
      laryngeal findings using the Reflux Finding Score (RFS) and the Reflux Symptom
      Index (RSI) and the objective voice quality using Jitter (JITT), Pitch Period
      Perturbation Quotient (PPQ), Shimmer (Shim), Amplitude Perturbation Quotient
      (APQ) and Noise-to-Harmonic Ratio (NHR) was examined. METHODS: Seventy-seven
      patients with SS and seventy-seven healthy individuals for the control group were
      studied. The Reflux Symptom Index (RSI); nine-item outcomes instrument for
      assessment of symptoms in patients and the Reflux Finding Score (RFS), eight-item
      laryngoscopic-based scale for evaluation of laryngeal findings in patients were
      realised. The Multi Dimensional Voice Program (MDVP) was used for capturing and
      analysis of the voice samples. For comparison of all parameters of patients and
      control group subjects, the independent sample t-test was used. RESULTS: The
      difference of RSI and RFS between patients with SS and control subjects was
      statistically significant. The difference of voice quality parameters between
      patients with SS and control subjects expect NHR were statistically significant.
      CONCLUSION: There is a significant association between SS and a variety of
      laryngeal pathologies. The SS patients with reflux symptoms and voice problems
      must be examined by an ENT specialist and local laryngeal manifestations of SS
      can be treated symptomatically.

PMID- 16095857
TI  - Preparation and characterization of a copper based Indian traditional drug: tamra
      bhasma.
AB  - The copper based Indian traditional drug 'tamra bhasma' is administered for
      various ailments since long. Its synthesis involves treating metallic copper with
      plant juices and then repeated calcination in presence of air so that the
      metallic state is transformed into the corresponding oxide form traditionally
      known as 'bhasma'. In this work, we present a systematic characterization of this
      traditional drug using various techniques like X-ray diffraction (XRD), scanning
      electron microscopy (SEM)-energy dispersive X-ray analysis (EDX), X-ray
      photoelectron spectroscopy (XPS), infrared spectroscopy (IR), thermogravimetry
      (TG) and surface area measurement. The results obtained were found to match very
      well with those of a standard copper oxide confirming the composition of the drug
      sample. In addition, some specific findings were also made which could help in
      interpreting the therapeutic properties of the traditional drug 'tamra bhasma'.

PMID- 16095858
TI  - Separation and determination of clotrimazole, methylparaben and propylparaben in
      pharmaceutical preparation by micellar electrokinetic chromatography.
AB  - In this study, micellar electrokinetic chromatography (MEKC) method was developed
      for the determination of clotrimazole (CLO), methylparaben (MP) and propylparaben
      (PP) in a pharmaceutical preparation. Separation was carried out in a fused
      silica capillary (60 cm x 75 microm i.d.) at 25 kV with UV detection at 212 nm.
      Optimized background electrolyte (BGE) was 15 mM phosphate buffer (pH 7.2)
      containing 30 mM sodium dodecyl sulfate (SDS) as a surfactant. Rectilinear
      calibration ranges were 50-500 mg l(-1) for CLO, 10-100 mg l(-1) for MP and 2.5
      25 mg l(-1) for PP. The total analysis time was < 12 min.

PMID- 16095859
TI  - Preparation and characterization of inclusion complexes of prazosin hydrochloride
      with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin.
AB  - The slightly water-soluble drug prazosin hydrochloride (PRH) and its inclusion
      with either beta-cyclodextrin (betaCD) or hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) were investigated. The phase solubility profiles of PRH with betaCD
      and HPbetaCD were classified as B(s)- and A(L)-types, respectively. Stability
      constants with 1:1 molar ratio were calculated from the phase solubility diagrams
      and the solubility of PRH could be enhanced by 27.6% for betaCD and 226.4% for
      HPbetaCD, respectively. Binary systems of PRH with betaCD or HPbetaCD prepared by
      various methods were characterized by differential scanning calorimetry and
      Fourier transformation-infrared spectroscopy. It could be concluded that PRH
      could form inclusion complex with either betaCD or HPbetaCD. The dissolution
      profiles of inclusion complexes were determined and compared with those of PRH
      alone and their physical mixtures. The dissolution rate of PRH was increased by
      betaCD and HPbetaCD inclusion complexation remarkably. Both the preparation
      technique and nature of the carriers played important roles in the dissolution
      performance of the systems. All the systems with HPbetaCD showed better
      performance than the corresponding ones with betaCD.

PMID- 16095860
TI  - CYP3A4 activity in four different animal species liver microsomes using 7
      benzyloxyquinoline and HPLC/spectrofluorometric determination.
AB  - Some microplate-based direct assays with different fluorometric substrates have
      been developed, among which 7-benzyloxyquinoline (BOQ) has demonstrated the
      highest degree of selectivity for CYP3A subfamily. In our study, we firstly
      developed and validated an efficient, fast and cheap HPLC/spectrofluorometric
      analytical method to quantify 7-hydroxyquinoline (BOQ metabolite). Secondly, BOQ
      oxidation rate (1.95 +/- 0.24 microM/mg protein/min) was compared to that of
      midazolam (MDZ) (1.4 +/- 0.21 microM/mg protein/min), an other specific CYP3A
      probe. However, the difference did not reach statistically significance (test of
      Sign; p = 0.125, two tailed). Thirdly, the potential use of BOQ in other species
      than the rat (mouse, dog and monkey) was studied. The highest BOQ activity was
      observed in rat microsomes (3.75 micromol/mg protein/min) with lower P450 content
      (0.3 nmol/mg protein) compared to other species. Finally, the effect of CYP3A
      enzymes-selective inhibitor ketoconazole on the dealkylation of BOQ in control
      and dexamethasone (DM)-treated rat microsomes was studied. Ketoconazole
      inhibition potency was greater in control (IC(50) approximately 21.6 microM)
      compared to DM induced (IC(50) approximately 32.3 microM) microsomes. At
      concentrations greater than that considered to be enzyme-selective (e.g., 10-30
      microM), ketoconazole inhibitory activity did not rise significantly, and at the
      maximal concentration tested (1,000 microM) a nearly similar inhibition (76%) was
      observed than that at 50 microM concentration (68.2%).

PMID- 16095861
TI  - High-performance liquid chromatography method for determining alendronate sodium
      in human plasma by detecting fluorescence: application to a pharmacokinetic study
      in humans.
AB  - A high-performance liquid chromatographic (HPLC) method was developed using
      diethylamine (DEA) solid-phase extraction (SPE), 9-fluorenylmethyl derivative
      (FMOC) and fluorescence detection for quantifying alendronate in human plasma.
      Sample preparation involved a manual protein precipitation with trichloroacetic
      acid, a manual coprecipitation of the bisphosphonate with calcium phosphate and
      derivatization with 9-fluorenylmethyl chloroformate in citrate buffer at pH 11.9.
      Liquid chromatography was performed on a Capcell Pak C(18) column (4.6 mm x 150
      mm, 5 microm particles), using a gradient method starting with mobile phase
      acetonitrile/methanol-citrate/pyrophosphate buffer (32:68, v/v). The total run
      time was 25 min. The fluorometric detector was operated at 260 nm (excitation)
      and 310 nm (emission). Pamidronate was used as the internal standard. The limit
      of quantification was 1 ng/ml using 3 ml of plasma. The intra- and inter-day
      precision expressed as the relative standard deviation was less than 15%. The
      assay was applied to the analysis of samples from a pharmacokinetic study.
      Following the oral administration of 70 mg of alendronate sodium to volunteers,
      the maximum plasma concentration (C(max)) and elimination half-life were 40.94 +/
      19.60 ng/ml and 1.67 +/- 0.50 h, respectively. The method was demonstrated to be
      highly feasible and reproducible for pharmacokinetic studies including
      bioequivalence test of alendronate sodium in humans.

PMID- 16095862
TI  - Orthogonal extraction/chromatography and UPLC, two powerful new techniques for
      bioanalytical quantitation of desloratadine and 3-hydroxydesloratadine at 25
      pg/mL.
AB  - Validation of the bioanalytical method for determination of desloratadine and 3
      hydroxydesloratadine was conducted using ultra high pressure liquid
      chromatography (UPLC) in conjunction with mix mode solid phase extraction. The
      dynamic range of the assay was from 0.025 ng/mL to 10 ng/mL using 96-well solid
      phase extraction. On an UPLC system, the inter-run accuracy was better than 94.7%
      for desloratadine (n = 18) and 94.0% for 3-hydroxydesloratadine (n = 18). The
      between-run precision (%CV) ranged from 2.6% to 9.8% for desloratadine (n = 18)
      and 3.1% to 11.1% for 3-hydroxydesloratadine (n = 18). The limit of quantitation
      represented 0.478 pg and 0.525 pg of extracted material injected on-column for
      desloratadine and 3-hydroxydesloratadine, respectively. The total run time was
      slightly over 2 min per sample. The approach of orthogonal
      extraction/chromatography and UPLC significantly improves assay performance while
      also increasing sample throughput for drug development studies.

PMID- 16095863
TI  - Supercritical fluid chromatography/tandem mass spectrometric method for analysis
      of pharmaceutical compounds in metabolic stability samples.
AB  - Packed-column supercritical fluid chromatography (pSFC) coupled to an atmospheric
      pressure chemical ionization (APCI) source and a tandem mass spectrometer (MS/MS)
      for rapid and simultaneous determination of clozapine, ondansetron, tolbutamide
      and primidone in in vitro samples was developed in support of metabolic stability
      experiments. The effects of the eluent flow-rate and composition as well as the
      nebulizer temperatures on the ionization efficiency of the analytes in positive
      ion mode under normal phase pSFC conditions were studied. The metabolic stability
      of the test drug components through microsomal incubation by the proposed pSFC
      APCI/MS/MS approaches requiring approximately 1 min per samples were evaluated
      with respect to specificity, durability and accuracy. These metabolic stability
      results obtained by pSFC-MS/MS methods are in a good agreement with those
      obtained by fast high-performance liquid chromatography/tandem mass spectrometry
      (HPLC-MS/MS) method.

PMID- 16095864
TI  - Quantitative determination of gatifloxacin, levofloxacin, lomefloxacin and
      pefloxacin fluoroquinolonic antibiotics in pharmaceutical preparations by high
      performance liquid chromatography.
AB  - The objective of this research was to develop and validate analytical methods for
      quantitative determination of fluoroquinolones of third generation. Simple and
      rapid chromatographic method was developed and validated for quantitative
      determination of four quinolone antibiotics in tablets and injection
      preparations. The fluoroquinolones studied were gatifloxacin (GAT), levofloxacin
      (LEV), lomefloxacin (LOM) and pefloxacin (PEF). The quinolones were analyzed by
      using a LiChrospher 100 RP-18 column (5 microm, 125 mm x 4 mm) and a mobile phase
      constituted of water:acetonitrile (80:20, v/v) with 0.3% of triethylamine and pH
      adjusted to 3.3 with phosphoric acid. The flow rate was 1.0 mL/min and the
      analyses were performed using UV detector with wavelengths varying from 279 to
      295 nm. The analyses were performed at room temperature (24 +/- 2 degrees C). All
      fluoroquinolones were separated within 5 min. The calibration curves were linear
      (r>or=0.9999) over a concentration range from 4.0 to 24.0 microg/mL. The relative
      standard deviation (R.S.D.) was < 1.0% and average recovery was above 99.54%.

PMID- 16095865
TI  - Methionine alters Na+,K+-ATPase activity, lipid peroxidation and nonenzymatic
      antioxidant defenses in rat hippocampus.
AB  - In the present study we investigated the effect of methionine exposure of
      hippocampus homogenates on Na+,K+-ATPase activity from synaptic plasma membrane
      of rats. Results showed that methionine significantly decreased this enzyme
      activity. We also evaluated the effect of incubating glutathione (GSH) and trolox
      (alpha-tocopherol) alone or combined with methionine on Na+,K+-ATPase activity.
      The tested antioxidants per se did not alter the enzymatic activity, but
      prevented the inhibitory action of methionine on Na+,K+-ATPase activity,
      indicating that Met inhibitory effect was probably mediated by free radical
      formation. Besides, we tested the in vitro effect of methionine on some
      parameters of oxidative stress, namely chemiluminescence, thiobarbituric acid
      reactive substances (TBARS), total radical-trapping antioxidant potential (TRAP),
      as well as on the antioxidant enzyme activities catalase, glutathione peroxidase
      and superoxide dismutase in rat hippocampus. We observed that methionine
      significantly increased chemiluminescence and TBARS, decreased TRAP, but did not
      change the activity of the antioxidant enzymes. These findings suggest that
      reduction of Na+,K+-ATPase activity and induction of oxidative stress may be
      involved in the brain damage observed in human hypermethioninemia.

PMID- 16095866
TI  - Neonatal cerebral hypoxia-ischemia: involvement of FAK-dependent pathway.
AB  - Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase thought to play a
      major role in transducing extracellular matrix (ECM)-derived survival signals
      into cells. Thus, modulation of FAK activity may affect the linkage between ECM
      and signaling cascade to which it is connected and may participate in a variety
      of pathological settings. In the present study, we investigated the effect of
      neonatal cerebral hypoxia-ischemia (HI) on levels and tyrosine phosphorylation of
      focal adhesion kinase and the interaction of this enzyme with Src protein
      tyrosine kinase and adapter protein p130Cas, involved in FAK-mediated signaling
      pathway. The total amount of focal adhesion kinase as well as its phosphorylated
      form declined substantially to about 50% of the control between 24 and 48 h after
      the insult. Concomitantly a decreased association of FAK with its investigated
      molecular partners, Src kinase and p130Cas protein has been observed. This early
      response to brain hypoxia-ischemia was attenuated during prolonged recovery with
      almost complete return to control values at 7 days. These data are indicative of
      an involvement of FAK-dependent signaling pathway in the evolution of HI-induced
      neuronal degeneration.

PMID- 16095867
TI  - Overweight and obesity: the significance of a depressed mood.
AB  - OBJECTIVE: Comorbid depression has been found to increase morbidity in a variety
      of disorders. This study aimed to investigate whether the presence of depressive
      symptoms in overweight and obese people is related to increased specific eating
      psychopathology and decreased self-esteem. METHODS: Overweight/obese people
      seeking dietary treatment were grouped according to their scores on the Beck
      Depression Inventory (BDI), resulting in a mildly to moderately depressed group
      (BDI > or = 10; n = 66; the symptomatic group) and a non-depressed group (BDI <
      10; n = 83). Eating psychopathology was measured by the Eating Disorder
      Examination-Questionnaire (EDE-Q); self-esteem was measured by the Rosenberg Self
      Esteem Scale. RESULTS: Symptomatic people had more shape, weight and eating
      concerns (P-values < 0.001); scored higher on restraint (P < 0.01); had lower
      self-esteem (P < 0.001); and had a higher BMI (P < 0.05) than non-depressed
      people. Furthermore, the percentage of bingers was higher in the symptomatic
      group (P < 0.01). CONCLUSION: Symptomatic participants suffered more than non
      depressed participants, and not only from their depression. PRACTICE
      IMPLICATIONS: For dieticians treating overweight and obese people, the BDI is a
      useful instrument for identifying the subgroup with depressive symptoms--the
      group that is at risk for (eating) psychopathology.

PMID- 16095868
TI  - Changes in reducing power profile of gastric juice in patients with active
      duodenal ulcer.
AB  - Reactive oxygen species have been postulated to play a role in the pathogenesis
      of mucosal GI injury and in peptic ulcer disease (PUD). The low molecular weight
      antioxidants (LMWA) group plays an important role in the defense mechanism of the
      GI tract against oxidative damage, and is a major component of the reducing
      capacity of biological tissues and fluids. We hypothesized that altered gastric
      LMWA anti oxidative status might play a role in the pathogenesis of upper GI
      disorders such as PUD and could be evaluated by measuring gastric juice reducing
      power. The aim of the present study was to determine, by cyclic voltammetry,
      changes in the overall antioxidant activity of the gastric juice in active
      duodenal ulcer (DU) obtained during upper endoscopy from patients as compared
      with normal subjects. The results show that in 28/37 (76%) of the control
      subjects, gastric juice demonstrated a reducing power of at least two anodic
      waves indicating at least two different LMWA groups. Three or more anodic waves
      were recorded in 12 normal subject (32%). In contrast, 16/25 (64%) of gastric
      juice samples obtained from active DU patients exhibited only one anodic wave
      usually at a high potential (>900 mV). These results imply that gastric juice
      normally possesses a reducing power profile that can be determined by cyclic
      voltammetry. This profile is significantly changed in untreated DU disease. These
      changes in active DU may indicate decreased gastric antioxidant activity
      reflecting reduced mucosal protection that leading to increased susceptibility of
      the gastro-duodenum to injury.

PMID- 16095869
TI  - Ecotoxicological evaluation of diethanolamine using a battery of microbiotests.
AB  - In order to investigate the potential ecotoxicity of diethanolamine (DEA), a
      battery of model systems was developed. DEA is widely used as a chemical
      intermediate and as a surface-active agent in cosmetic formulations,
      pharmaceuticals and agricultural products. DEA was studied using ecotoxicological
      model systems, representing four trophic levels, with several bioindicators
      evaluated at different exposure time periods. The battery included
      bioluminescence inhibition of the bacterium Vibrio fischeri, growth inhibition of
      the alga Chlorella vulgaris and immobilization of the cladoceran Daphnia magna.
      Cell morphology, total protein content, neutral red uptake, MTS metabolization,
      lysosomal function, succinate dehydrogenase activity, G6PDH activity,
      metallothionein levels and EROD activity were studied in the hepatoma fish cell
      line PLHC-1, derived from Poeciliopsis lucida. The systems most sensitive to DEA
      were both D. magna and V. fischeri, followed by C. vulgaris and the fish cell
      line PLHC-1. The most prominent morphological effect observed in PLHC-1 cultures
      exposed to DEA was the induction of a marked steatosis, followed by death at high
      concentrations, in some cases by apoptosis. The main biochemical modification was
      a nearly three-fold increase in metallothionein levels, followed by the
      stimulations of lysosomal function and succinate dehydrogenase and G6PDH
      activities. Judging by the EC(50) values in the assay systems, DEA is not
      expected to produce acute toxic effects in the aquatic biota. However, chronic
      and synergistic effects with other chemicals cannot be excluded.

PMID- 16095870
TI  - Cytochrome P4501A induction caused by the imidazole derivative Prochloraz in a
      rainbow trout cell line.
AB  - A variety of aquatic pollutants are able to induce cytochrome P4501A (CYP1A) in
      fish by ligand binding to the aryl hydrocarbon receptor (AhR). High-affinity AhR
      ligands are planar aromatic polycyclic molecules such as the prototypical ligand,
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The present work investigates the
      ability of the imidazole derivative, Prochloraz (PRO), to induce CYP1A.
      Computational studies on the molecular structure of PRO indicated that it is
      highly unlikely for PRO to have both aromatic rings of the molecule, i.e. the
      imidazole and the benzene ring, in the same plane. Thus, the possible conformers
      do not take planar structures, in contrast to the typically planar AhR ligands.
      Experimentally, the capability of PRO to induce CYP1A was assessed using the
      rainbow trout liver cell line, RTL-W1, as in vitro model. PRO increased in a
      concentration-dependent way the catalytic activity of CYP1A (determined as 7
      ethoxyresorufin-O-deethylase, EROD, activity) in RTL-W1 cells. The potency of PRO
      was lower than that of a reference AhR-ligand, beta-naphthoflavone (betaNF). In
      addition to the catalytic level, PRO activated CYP1A also at the transcriptional
      level as determined by RT-PCR analysis of CYP1A mRNA. These results indicate that
      PRO, although its structure is not corresponding to the typical features of CYP1A
      inducing AhR ligands, still is able to activate CYP1A expression.

PMID- 16095871
TI  - Misuse of statistical tests in Archives of Clinical Neuropsychology publications.
AB  - This article reviews the (mis)use of statistical tests in neuropsychology
      research studies published in the Archives of Clinical Neuropsychology in the
      years 1990-1992 and 1996-2000, and 2001-2004, prior to, commensurate with the
      internet-based and paper-based release, and following the release of the American
      Psychological Association's Task Force on Statistical Inference. The authors
      focused on four statistical errors: inappropriate use of null hypothesis tests,
      inappropriate use of P-values, neglect of effect size, and inflation of Type I
      error rates. Despite the recommendations of the Task Force on Statistical
      Inference published in 1999, the present study recorded instances of these
      statistical errors both pre- and post-APA's report, with only the reporting of
      effect size increasing after the release of the report. Neuropsychologists
      involved in empirical research should be better aware of the limitations and
      boundaries of hypothesis testing as well as the theoretical aspects of research
      methodology.

PMID- 16095873
TI  - Effects of vocal constitution and autonomic stress-related reactivity on vocal
      endurance in female student teachers.
AB  - Several studies revealed a high percentage of voice problems in future teachers.
      The influence of vocal constitution on the vocal endurance is, however, still
      unclear. The goal of this study was to evaluate whether the increase of voice
      fundamental frequency (F0) during teaching is caused by (1) autonomic regulation
      patterns under stress, (2) anxiety as an emotional factor, or (3) limitations in
      voice constitution. Thirty-three subjects with either normal voice constitution
      (n = 15, group 1) or constitutional hypofunction (n = 18, group 2) assessed by
      voice range profile measurements were enrolled in this study. Furthermore, they
      underwent a standardized baseline test to register selected autonomic test
      parameters and were classified into autonomic outlet types (AOT) as proposed by
      Johannes et al. Later the subjects were examined during 1 hour of teaching (field
      study). The parameters tested included heart rate, pulse transition time, finger
      temperature, and voice fundamental frequency. To measure situational anxiety and
      general anxiety proneness, a state-trait anxiety inventory was taken. Eleven
      subjects per group were identified as autonomic stable (AOT 1), two per group as
      responding cardiovascularly (AOT 2), and two of group 1 and four of group 2,
      respectively, as having higher heart rate and higher blood pressure responses to
      stress (AOT 4). One subject had to be excluded because of missing data. However,
      statistical analyses showed no differences between AOT groups regarding the voice
      constitution groups. Increased fundamental frequencies of speaking voice after 30
      and 45 minutes of teaching were found in group 2 (constitutional hypofunction).
      No effect of state or trait anxiety on voice endurance could be detected. Thus,
      the increase of fundamental frequency of voice has to be regarded as a
      consequence of vocal fatigue. A constitutionally weak voice seems to be a risk
      factor for developing a professional voice disorder.

PMID- 16095872
TI  - Differential effects on [35S]GTPgammaS binding using muscarinic agonists and
      antagonists in the gerbil brain.
AB  - In this work, we studied the in vitro G-protein activation induced by muscarinic
      agonists using [(35)S]guanylyl-5'-O-(gamma-thio)-triphosphate ([(35)S]GTPgammaS)
      autoradiographic methods to characterize the M(2) and M(4) muscarinic subtypes
      response. Thus, we describe a detailed characterization of the increases in
      [(35)S]GTPgammaS binding elicited by carbachol (Cch) and oxotremorine (OXO)
      (binding in the presence minus binding in the absence of agonist) throughout the
      gerbil brain (Meriones unguiculatus). For both agonists, the strongest
      stimulations were found in the superficial gray layer of the superior colliculus,
      the anteroventral and anteromedial thalamic nuclei, the anterior paraventricular
      thalamic nucleus, and the caudate-putamen. The comparative study using OXO and
      Cch suggested that OXO is able to detect differences in the response of
      structures enriched in M(4) muscarinic receptors, showing a lower potency to
      stimulate these brain areas. Furthermore, using increasing concentrations of
      selective M(2) (AF-DX 116) and M(1)/M(4) (pirenzepine) antagonists to inhibit
      specific Cch- or OXO-induced [(35)S]GTPgammaS binding, significant differences
      were observed in M(2)-enriched structures but not in M(4)-enriched ones such as
      the caudate-putamen. These data indicate that appropriate muscarinic agonist
      stimulation, together with selective inhibition of this effect using functional
      autoradiography, can be used as a tool to unravel the M(2)- and M(4)-muscarinic
      subtype-mediated response.

PMID- 16095874
TI  - Training neural networks with heterogeneous data.
AB  - Data pruning and ordered training are two methods and the results of a small
      theory that attempts to formalize neural network training with heterogeneous
      data. Data pruning is a simple process that attempts to remove noisy data.
      Ordered training is a more complex method that partitions the data into a number
      of categories and assigns training times to those assuming that data size and
      training time have a polynomial relation. Both methods derive from a set of
      premises that form the 'axiomatic' basis of our theory. Both methods have been
      applied to a time-delay neural network-which is one of the main learners in
      Microsoft's Tablet PC handwriting recognition system. Their effect is presented
      in this paper along with a rough estimate of their effect on the overall multi
      learner system. The handwriting data and the chosen language are Italian.

PMID- 16095875
TI  - Optimizing conductance parameters of cortical neural models via electrotonic
      partitions.
AB  - Development of automated methods for fitting computational models to observed
      biological data is an important challenge of neural modeling. Previous work has
      focused on generalized search techniques combined with distance measures tuned to
      specific neural morphologies. We propose general analysis techniques to guide
      construction of distance measures across a broader range of cell types.
      Specifically, we evaluate the use of multiple external stimuli to evoke
      characteristic behaviors of underlying active channel densities on a simple three
      compartment model. We also examine the use of frequency analysis to smooth search
      space distortions induced by temporal shifts in recorded voltage traces. We
      propose a novel method of parameter optimization that is characterized by linear
      regression over the conductance densities using channel permissiveness as a basis
      of ionic current. We derive this method and demonstrate, given known anatomy and
      kinetics, it will solve all conductance densities in an N compartment model given
      N spatially distinct membrane potential traces with minimal error. We compare the
      regression method with the covariance matrix adaptation evolutionary strategy
      (CMA-ES) over a two-compartment cortical neuron and empirically show that
      regression over electrotonic partitions solves the cortical model near-optimally.
      We also show that electronic partitioning significantly improves search
      performance of CMA-ES on the cortical model.

PMID- 16095876
TI  - Quantifying information and performance for flash detection in the blowfly
      photoreceptor.
AB  - Performance on specific tasks in an organism's everyday activities is essential
      to survival. In this paper, we extend information-theoretic investigation of
      neural systems to task specific information using a detailed biophysical model of
      the blowfly photoreceptor. We determine the optimal detection performance using
      ideal observer analysis and find that detection threshold increases with
      background light according to a power function. We show how Fisher information is
      related to the detection performance and compare Fisher information and mutual
      information in this task-specific context. Our detailed model of the blowfly
      photoreceptor enables us to detangle the components of phototransduction and
      analyze the sensitivity of detection performance with respect to biophysical
      parameters. The biophysical model of the blowfly photoreceptor provides a rich
      framework for investigation of neural systems.

PMID- 16095877
TI  - FPGA implementation of self organizing map with digital phase locked loops.
AB  - The self-organizing map (SOM) has found applicability in a wide range of
      application areas. Recently new SOM hardware with phase modulated pulse signal
      and digital phase-locked loops (DPLLs) has been proposed (Hikawa, 2005). The
      system uses the DPLL as a computing element since the operation of the DPLL is
      very similar to that of SOM's computation. The system also uses square waveform
      phase to hold the value of the each input vector element. This paper discuss the
      hardware implementation of the DPLL SOM architecture. For effective hardware
      implementation, some components are redesigned to reduce the circuit size. The
      proposed SOM architecture is described in VHDL and implemented on field
      programmable gate array (FPGA). Its feasibility is verified by experiments.
      Results show that the proposed SOM implemented on the FPGA has a good
      quantization capability, and its circuit size very small.

PMID- 16095878
TI  - A model of STDP based on spatially and temporally local information: derivation
      and combination with gated decay.
AB  - Temporal relationships between neuronal firing and plasticity have received
      significant attention in recent decades. Neurophysiological studies have shown
      the phenomenon of spike-timing-dependent plasticity (STDP). Various models were
      suggested to implement an STDP-like learning rule in artificial networks based on
      spiking neuronal representations. The rule presented here was developed under
      three constraints. First, it only depends on the information that is available at
      the synapse at the time of synaptic modification. Second, it naturally follows
      from neurophysiological and psychological research starting with Hebb's postulate
      [D. Hebb. (1949). The organization of behavior. Wiley, New York]. Third, it is
      simple, computationally cheap and its parameters are straightforward to
      determine. This rule is further extended by addition of four different types of
      gating derived from conventionally used types of gated decay in learning rules
      for continuous firing rate neural networks. The results show that the advantages
      of using these gatings are transferred to the new rule without sacrificing its
      dependency on spike-timing.

PMID- 16095879
TI  - Metastability, instability, and state transition in neocortex.
AB  - Mesoscopic patterns of neural activity were sought in multichannel EEGs of
      rabbits that were trained to respond to conditioned stimuli (CSs) in visual,
      auditory and somatic modalities. Spatiotemporal patterns were sought of
      oscillations in the beta and gamma ranges. The techniques required for
      preprocessing EEGs in search of global patterns were diametrically opposed to
      those needed for localization of modular EEG signals. Frames were found in the
      form of intermittent spatial patterns of phase and amplitude modulation (AM and
      PM) of carrier waves in beta and gamma ranges that served to classify EEG frames
      with respect to CSs. A model based on the intentional action-perception cycle is
      proposed to complement the information processing model.

PMID- 16095880
TI  - RGS2 interacts with Gs and adenylyl cyclase in living cells.
AB  - Regulator of G Protein Signalling (RGS) proteins impede heterotrimeric G protein
      signalling. RGS2 decreases cAMP production and appears to interact with both
      adenylyl cyclase (AC) and its stimulatory G protein Gs. We showed previously that
      Green Fluorescent Protein-tagged RGS2 (GFP-RGS2) localizes to the nucleus in HEK
      293 cells and is recruited to the plasma membrane when co-expressed with Gsalpha,
      or the Gs-coupled beta2-adrenergic receptor (beta2AR). Here, using confocal
      microscopy we show that co-expression of various AC isoforms (ACI, ACII, ACV,
      ACVI) also leads to GFP-RGS2 recruitment to the plasma membrane. Bioluminescence
      Resonance Energy Transfer (BRET) was also used to examine physical interactions
      between RGS2 and components of the Gs-signalling pathway. A BRET signal was
      detected between fusion constructs of RGS2-Renilla luciferase (energy donor) and
      Gsalpha-GFP (energy acceptor) co-expressed in HEK 293 cells. BRET was also
      observed between GFP-RGS2 and ACII or ACVI fused to Renilla luciferase.
      Additionally, RGS2 was found to interact with the beta2AR. Purified RGS2
      selectively bound to the third intracellular loop of the beta2AR in GST pulldown
      assays, and a BRET signal was observed between GFP-RGS2 and beta2AR fused to
      Renilla luciferase when these two proteins were co-expressed together with either
      ACIV or ACVI. This interaction was below the limit of detection in the absence of
      co-expressed AC, suggesting that the effector enzyme stabilized or promoted
      binding between the receptor and the RGS protein inside the cell. Taken together,
      these results suggest the possibility that RGS2 might bind to a receptor-G
      protein-effector signalling complex to regulate Gs-dependent cAMP production.

PMID- 16095881
TI  - Insulin rapidly upregulates protein kinase Cdelta gene expression in skeletal
      muscle.
AB  - Recent studies in our laboratories have shown that Protein Kinase C delta
      (PKCdelta) is essential for insulin-induced glucose transport in skeletal muscle,
      and that insulin rapidly stimulates PKCdelta activity skeletal muscle. The
      purpose of this study was to examine mechanisms of regulation of PKCdelta protein
      availability. Studies were done on several models of mammalian skeletal muscle
      and utilized whole cell lysates of differentiated myotubes. PKCdelta protein
      levels were determined by Western blotting techniques, and PKCdelta RNA levels
      were determined by Northern blotting, RT-PCR and Real-Time RT-PCR. Insulin
      stimulation increased PKCdelta protein levels in whole cell lysates. This effect
      was not due to an inhibition by insulin of the rate of PKCdelta protein
      degradation. Insulin also increased 35S-methionine incorporation into PKCdelta
      within 5-15 min. Pretreatment of cells with transcription or translation
      inhibitors abrogated the insulin-induced increase in PKCdelta protein levels. We
      also found that insulin rapidly increased the level of PKCdelta RNA, an effect
      abolished by inhibitors of transcription. The insulin-induced increase in
      PKCdelta expression was not reduced by inhibition of either PI3 Kinase or MAP
      kinase, indicating that these signaling mechanisms are not involved, consistent
      with insulin activation of PKCdelta. Studies on cells transfected with the
      PKCdelta promoter demonstrate that insulin activated the promoter within 5 min.
      This study indicates that the expression of PKCdelta may be regulated in a rapid
      manner during the course of insulin action in skeletal muscle and raise the
      possibility that PKCdelta may be an immediate early response gene activated by
      insulin.

PMID- 16095882
TI  - Two distinct Ca2+ compartments show differential sensitivity to thrombin, ADP and
      vasopressin in human platelets.
AB  - Recent studies propose the existence of two distinct Ca2+ compartments in human
      platelets based on the expression of different SERCA isoforms with distinct
      sensitivity to thapsigargin and 2,5-di-(tert-butyl)-1,4-hydroquinone (TBHQ).
      Using fura-2-loaded human platelets we have found that depletion of the TBHQ
      sensitive store reduces thrombin--but not ADP--or vasopressin (AVP)-induced Ca2+
      release. Redistribution of cytosolic Ca2+ after thrombin stimulation resulted in
      overloading of the TBHQ-sensitive store. This phenomenon was not observed with
      ADP or AVP. We found that NAADP decreases the Ca2+ concentration into the stores
      in permeabilized platelets, which is prevented by depletion of the TBHQ-sensitive
      store. Nimodipine, an inhibitor of the NAADP receptor, reduced thrombin-induced
      Ca2+ release from the TBHQ-sensitive stores, without having any effect on the
      responses elicited by ADP or AVP. Finally, the phospholipase C inhibitor, U
      73122, abolished ADP- and AVP-induced Ca2+ release, suggesting that their
      responses are entirely dependent on IP3 generation. In contrast, treatment with
      both U-73122 and nimodipine was required to abolish thrombin-induced Ca2+
      release. We suggest that thrombin evokes Ca2+ release from TBHQ-sensitive and
      insensitive stores, which requires both NAADP and IP3, respectively, while ADP
      and AVP exert an IP3-dependent release of Ca2+ from the TBHQ-insensitive
      compartment in human platelets.

PMID- 16095883
TI  - Craving and other characteristics of the comorbidity of alcohol and nicotine
      dependence.
AB  - PURPOSE: In this cross-sectional study we compared alcohol-dependent smokers and
      non-alcohol-dependent smokers with respect to intensity of nicotine dependence,
      craving conditions, sleep disturbances, comorbidity with major depression,
      reasons for smoking, accompanying somatic diseases and patients' prolonged
      abstinence from smoking during the 3 years preceding the study. SUBJECTS AND
      METHODS: Fifty-one alcohol-dependent smokers and 327 non-alcohol-dependent
      smokers diagnosed as ICD-10 and DSM-IV-nicotine dependent, were investigated by
      means of the Fagerstrom Test for Nicotine Dependence, the Lubeck Craving
      Recurrence Risk Questionnaire and the Lesch Alcohol Dependence Typology (both
      adapted to smoking). RESULTS: The intensity of nicotine dependence was more
      enhanced in alcohol-dependent smokers compared to non-alcohol-dependent smokers.
      Several variables of all factors of craving ("depressive mood", "stimulation",
      "relaxation", "socially triggered tension") were significantly increased in
      alcohol-dependent patients (P<0.05). Alcohol-dependent smokers showed depressive
      symptoms and sleep disturbances, whilst non-alcohol-dependent individuals mainly
      smoked for stress release and weight control. DISCUSSION: Our study demonstrates
      that the intensity of nicotine dependence, several conditions of craving for
      nicotine, sleep disturbances and symptoms of depression appear to be enhanced in
      alcohol-dependent smokers compared with non-alcohol-dependent smokers.
      Conclusions. - It is hoped that the factors of craving and reasons for smoking
      identified in this study will contribute to a better understanding of smoking
      temptation in alcohol-dependent smokers and non-alcohol-dependent smokers in
      future.

PMID- 16095884
TI  - Cognitive evaluation of disease-modifying efficacy of galantamine and memantine
      in the APP23 model.
AB  - With increasing knowledge of molecular, biochemical and cellular events causing
      synaptic dysfunction and neurodegeneration in Alzheimer-diseased brain,
      preventive treatment strategies are emerging. Neuroprotective capacities have
      been attributed to galantamine and memantine. The age-dependent cognitive decline
      in the APP23 model was employed to evaluate disease-modifying efficacy of chronic
      treatment with both compounds. At age 6 weeks, heterozygous APP23 mice were
      subcutaneously implanted with osmotic pumps delivering saline, galantamine (1.3
      or 2.6 mg/kg/day) or memantine (7.2 or 14.4 mg/kg/day). After 2 months of
      treatment, a 3-week wash-out period was allowed to prevent bias from sustained
      symptomatic effects. Subsequently, cognitive evaluation in the Morris water maze
      commenced. Galantamine low dose significantly improved spatial accuracy during
      probe trial. Memantine improved acquisition performance (path length) and spatial
      accuracy during probe trial in a dose-dependent manner. This is the first study
      reporting disease-modifying efficacy of galantamine and memantine in transgenic
      mice modeling Alzheimer's disease.

PMID- 16095885
TI  - LRP 1 B functions as a receptor for Pseudomonas exotoxin.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that produces several
      virulence factors, among them Pseudomonas Exotoxin A (PE). Previously, low
      density lipoprotein receptor-related protein 1 (LRP 1) was shown to be the
      primary receptor for PE. In this report, we show that a close family member, LRP
      1B, can also function as a receptor.

PMID- 16095886
TI  - Learning and decision making in monkeys during a rock-paper-scissors game.
AB  - Game theory provides a solution to the problem of finding a set of optimal
      decision-making strategies in a group. However, people seldom play such optimal
      strategies and adjust their strategies based on their experience. Accordingly,
      many theories postulate a set of variables related to the probabilities of
      choosing various strategies and describe how such variables are dynamically
      updated. In reinforcement learning, these value functions are updated based on
      the outcome of the player's choice, whereas belief learning allows the value
      functions of all available choices to be updated according to the choices of
      other players. We investigated the nature of learning process in monkeys playing
      a competitive game with ternary choices, using a rock-paper-scissors game. During
      the baseline condition in which the computer selected its targets randomly, each
      animal displayed biases towards some targets. When the computer exploited the
      pattern of animal's choice sequence but not its reward history, the animal's
      choice was still systematically biased by the previous choice of the computer.
      This bias was reduced when the computer exploited both the choice and reward
      histories of the animal. Compared to simple models of reinforcement learning or
      belief learning, these adaptive processes were better described by a model that
      incorporated the features of both models. These results suggest that stochastic
      decision-making strategies in primates during social interactions might be
      adjusted according to both actual and hypothetical payoffs.

PMID- 16095887
TI  - Naming of newly learned objects: a PET activation study.
AB  - The present study tracked the naming-related brain activity by positron emission
      tomography (PET) when successfully learned unfamiliar objects were named. Ten
      Finnish-speaking subjects participated in the study. Prior to the PET scan, each
      subject underwent a 4-day long training period in which 40 names of rare
      unfamiliar objects were taught. The stimulus categories were as follows:
      unfamiliar but real objects for which both the name and the definition were given
      during training, only the name was given, no information was given. In addition,
      familiar objects and visual noise patterns were used. The unfamiliar items mainly
      represented ancient domestic tools unknown to modern-day people. As semantic
      support did not affect the PET results, all trained items were pooled together.
      The trained objects vs. familiar objects contrast revealed rCBF increases in the
      left inferior frontal cortex (Broca's area), the left anterior temporal area, and
      the cerebellum. Likewise, the trained objects vs. unfamiliar objects (for which
      no information was given) contrast revealed more extensive left frontal (roughly
      Broca's area) and cerebellar rCBF increases, while anterior temporal activation
      was bilateral. Familiar objects, contrasted with both visual noise patterns and a
      rest condition, elicited activation increases in expected areas, i.e., bilateral
      occipital regions and the fusiform gyrus. Our results indicate that the naming of
      newly learned objects recruits more extensive brain areas than the naming of
      familiar items, namely a network that includes left-dominant frontotemporal areas
      and cerebellum. Its activity is tentatively related to enhanced lexical-semantic
      and lexical-phonological retrieval, as well as associative memory processes.

PMID- 16095888
TI  - Advanced soft computing diagnosis method for tumour grading.
AB  - OBJECTIVE: To develop an advanced diagnostic method for urinary bladder tumour
      grading. A novel soft computing modelling methodology based on the augmentation
      of fuzzy cognitive maps (FCMs) with the unsupervised active Hebbian learning
      (AHL) algorithm is applied. MATERIAL AND METHODS: One hundred and twenty-eight
      cases of urinary bladder cancer were retrieved from the archives of the
      Department of Histopathology, University Hospital of Patras, Greece. All tumours
      had been characterized according to the classical World Health Organization (WHO)
      grading system. To design the FCM model for tumour grading, three experts
      histopathologists defined the main histopathological features (concepts) and
      their impact on grade characterization. The resulted FCM model consisted of nine
      concepts. Eight concepts represented the main histopathological features for
      tumour grading. The ninth concept represented the tumour grade. To increase the
      classification ability of the FCM model, the AHL algorithm was applied to adjust
      the weights of the FCM. RESULTS: The proposed FCM grading model achieved a
      classification accuracy of 72.5%, 74.42% and 95.55% for tumours of grades I, II
      and III, respectively. CONCLUSIONS: An advanced computerized method to support
      tumour grade diagnosis decision was proposed and developed. The novelty of the
      method is based on employing the soft computing method of FCMs to represent
      specialized knowledge on histopathology and on augmenting FCMs ability using an
      unsupervised learning algorithm, the AHL. The proposed method performs with
      reasonably high accuracy compared to other existing methods and at the same time
      meets the physicians' requirements for transparency and explicability.

PMID- 16095889
TI  - Computational intelligence in solving bioinformatics problems.

PMID- 16095890
TI  - Alpha 2(I) collagen deficient oim mice have altered biomechanical integrity,
      collagen content, and collagen crosslinking of their thoracic aorta.
AB  - Collagen and elastin are the primary determinants of vascular integrity, with
      elastin hypothesized to be the major contributor to aortic compliance and type I
      collagen the major contributor to aortic strength and stiffness. Type I collagen
      is normally heterotrimeric composed of two alpha1(I) and one alpha2(I) collagen
      chains, alpha1(I)(2)alpha2(I). Recent investigations have reported that patients
      with recessively inherited forms of Ehlers Danlos syndrome that fail to
      synthesize proalpha2(I) chains have increased risks of cardiovascular
      complications. To assess the role of alpha2(I) collagen in aortic integrity, we
      used the osteogenesis imperfecta model (oim) mouse. Oim mice, homozygous for a
      COL1A2 mutation, synthesize only homotrimeric type I collagen, alpha1(I)3. We
      evaluated thoracic aortas from 3-month-old oim, heterozygote, and wildtype mice
      biomechanically for circumferential breaking strength (Fmax) and stiffness (IEM),
      histologically for morphological differences, and biochemically for collagen
      content and crosslinking. Circumferential biomechanics of oim and heterozygote
      descending thoracic aortas demonstrated the anticipated reduced Fmax and IEM
      relative to wildtype mice. Histological analyses of oim descending aortas
      demonstrated reduced collagen staining relative to wildtype aortas suggesting
      decreased collagen content, which hydroxyproline analyses of ascending and
      descending oim aortas confirmed. These findings suggest the reduced oim thoracic
      aortic integrity correlates with the absence of the alpha2(I)collagen chains and
      in part with reduced collagen content. However, oim ascending aortas also
      demonstrated a significant increase in pyridinoline crosslinks/collagen molecule
      as compared to wildtype ascending aortas. The role of increased collagen
      crosslinks is uncertain; increased crosslinking may represent a compensatory
      mechanism for the decreased integrity.

PMID- 16095891
TI  - Iloprost treatment reduces TNF-alpha production and TNF-RII expression in
      critical limb ischemia patients without affecting IL6.
AB  - Iloprost, a stable prostacyclin analogue, regulates expression of genes that are
      involved in inflammation and in cell growth and inhibits the in vitro production
      of cytokines. We evaluated the effect of an in vivo weekly iloprost treatment on
      TNF-alpha and IL6 monocyte production (evaluated by ELISA), on monocyte apoptosis
      (Annexin V/uptake of propidium iodide by flow cytometry) and on peripheral blood
      mononuclear cell (PBMC) TNF-alpha receptors (TNF-RI and TNF-RII) mRNA expression
      (RT-PCR) in 14 atherosclerotic critical limb ischemia patients. PBMC were
      stimulated with LPS for 24h. TNF-alpha production was significantly reduced by
      iloprost whereas IL6 production was not affected. Iloprost did not accelerate
      monocyte apoptosis. TNF-RI mRNA expression was not modified by iloprost, whereas
      TNF-RII mRNA expression was significantly reduced. Our data show that iloprost
      may have anti-inflammatory effects in addition to the well-known vasodilatatory
      and anti-aggregant ones.

PMID- 16095892
TI  - Using the lower limits. Only for FEV6?

PMID- 16095893
TI  - Effects of nebulized sodium cromoglycate on adult patients with severe refractory
      asthma.
AB  - Many patients with severe refractory asthma, which is insufficiently controlled
      by additional high-dose of inhaled corticosteroids, require oral corticosteroids
      and/or immunosuppressant. Clinicians should seek for suitable medications, for
      its' chronic use may induce high risk of side effects. The purpose of this study
      was to evaluate the efficacy and safety of nebulized sodium cromoglycate (3-4
      times/day) in adult severe asthmatic patients with poorly controlled asthmatic
      symptoms, despite treatments with high-dose inhaled corticosteroids. Adult
      patients with severe asthma (n=251) were enrolled in a randomized clinical trial
      at 30 medical centers in Japan. Isotonic saline was used as placebo. The study
      was conducted for 10 weeks; with initial 2 weeks of observation followed by 8
      weeks of treatments. Efficacy was primarily evaluated based on improvements in
      morning peak expiratory flow after treatment. All patients who applied inhalation
      of nebulized sodium cromoglycate (SCG group) or saline (Controls) were treated
      with high-dose of inhaled corticosteroids (median of beclomethasone dipropionate
      equivalent dose: 1600 microg/days) and second-line control therapy including oral
      corticosteroids. There was no significant difference in morning peak expiratory
      flow between SCG group and controls. However, when patients were stratified into
      atopic and non-atopic groups, morning peak expiratory flow had significantly
      improved in the atopic SCG group compared to atopic Controls. Additional
      inhalation of nebulized sodium cromoglycate with inhaled corticosteroids is
      effective even in patients with severe atopic asthma. This finding shows that
      nebulized sodium cromoglycate is expected to be new second-line therapeutic
      option in severe asthma.

PMID- 16095894
TI  - Analysis of protein interactions on protein arrays by a novel spectral surface
      plasmon resonance imaging.
AB  - We presented a novel surface plasmon resonance (SPR) imaging method for analysis
      of protein arrays based on a wavelength interrogation-based SPR biosensor. The
      spectral imaging was performed by the combination of position control and
      resonance wavelengths calculated from SPR reflectivity spectra. The imaging
      method was evaluated by analyzing interactions of glutathione S-transferase
      fusion proteins with their antibodies. Antigen-antibody interactions were
      successfully analyzed on glutathione S-transferase-fusion protein arrays by using
      the spectral imaging method, and the results were confirmed by a parallel
      analysis using a previously used spectral SPR biosensor based on wavelength
      interrogation. Specific binding of anti-Rac1 and anti-RhoA to Rac1 and RhoA on
      the protein arrays was qualitatively and quantitatively analyzed by the spectral
      SPR imaging. Thus, it was suggested that the novel spectral SPR imaging was a
      useful tool for the high-throughput analysis of protein-protein interactions on
      protein arrays.

PMID- 16095895
TI  - Amplified label-free electrocatalytic detection of DNA in the presence of calcium
      ions.
AB  - A new label-free electrocatalytic method for the detection of DNA, is presented,
      in which DNA is the catalyst. The method takes advantage of the catalytic
      properties of the electrooxidised adenines within DNA toward the oxidation of
      NADH. This catalytic event results in an enhancement in the oxidation current of
      the electrooxidised adenines within DNA. Further improvement in this analytical
      signal is achieved in the presence of Ca(2+) ions. Parameters affecting the
      electrocatalytic current, such as pH or concentration of Ca(2+) ions have been
      investigated and optimised. Finally, the analytical features of the developed
      method are obtained. This method constitutes a more sensitive and reproducible
      alternative to other methods that use the oxidation current of the
      electrooxidised adenines without coupling to any catalytic event. A limit of
      detection of 33 fmol deoxyadenylic acid icosanucleotide (dA)(20), is obtained
      without labels.

PMID- 16095896
TI  - Nanoparticle-assisted micropatterning of active proteins on solid substrate.
AB  - Micropatterning of proteins on silica substrate was achieved using a new method.
      Proteins were first immobilized onto silica nanoparticles which were then
      dispensed into arrayed microwells on silicon. Atomic force microscopy (AFM),
      fluorescence microscopy and Fourier transform infrared (FTIR) spectroscopy were
      used to characterize the samples. The results showed that, compared to a planar
      surface, curved surfaces of nanoparticles provide more space for attaching
      proteins and thus increases the intensity of fluorescence signal. Furthermore,
      after attaching to silica nanoparticles, bovine serum albumin (BSA) maintains its
      major structure and the cytokine IFN-gamma maintains its ability to bind to its
      antibody. Use of this method can be extended to micropatterning of other
      biomolecules, such as DNA and enzymes.

PMID- 16095897
TI  - Bacterial sensors based on Acidithiobacillus ferrooxidans Part I. Fe2+ and S2O32-
      determination.
AB  - An amperometric bacterial sensor with current response to Fe(2+) and S(2)O(3)(2-)
      ions has been designed by immobilizing an acidophilic biomass of
      Acidithiobacillus ferrooxidans on a multi disk flat-front oxygen probe. The
      bacterial layer was located between the oxygen probe and a membrane of cellulose.
      A filtration technique was used to yield the bacterial membranes having
      reproducible activity. The decrease of O(2) flow across the bacterial layer is
      proportional to the concentration of the dosed species. The dynamic range
      appeared to be linear for the Fe(2+) ions up to 2.5 mmol L(-1) with a detection
      limit of 9 x 10(-7) mol L(-1) and a sensitivity of 0.25 A L mol(-1). The response
      of the biosensor is 84 s for a determination of 2 x 10(-4) mol L(-1) Fe(2+).
      Optimizing the Fe(2+) determination by A. ferrooxidans sensor was carried out
      owing to Design of Experiments (DOE) methodology and empirical modelling. The
      optimal response was thus obtained for a pH of 3.4, at 35 degrees C under 290 rpm
      solution stirring. S(2)O(3)(2-) concentration was determined at pH 4.7, so
      avoiding its decomposition. The concentration range was linear up to 0.6 mmol L(
      1). Sensitivity was 0.20 A L mol(-1) with a response time of 207 s for a 2 x 10(
      4) mol L(-1) S(2)O(3)(2-) concentration.

PMID- 16095898
TI  - Preparative expression of secreted proteins in bacteria: status report and future
      prospects.
AB  - The expression of heterologous secreted proteins in Escherichia coli is widely
      employed for laboratory and preparative purposes. Thanks to advances in
      expression technologies over the past 25 years, many mammalian proteins can now
      be produced routinely in secreted form with yields in the gram/litre scale.
      Nonetheless, ensuring efficient secretion across the inner membrane, and
      preventing proteolytic degradation, incorrect disulfide-bond formation and
      aggregation into periplasmic inclusion bodies, frequently presents significant
      challenges. Recent advances in the understanding of the periplasmic folding
      quality control system are leading to new strategies to facilitate the expression
      of heterologous secreted proteins. In parallel, protein design and directed
      evolution approaches are beginning to be exploited for engineering of the
      cellular protein folding machinery to achieve further improvements in protein
      expression.

PMID- 16095899
TI  - The clearance of viruses and transmissible spongiform encephalopathy agents from
      biologicals.
AB  - The viral and transmissible spongiform encephalopathy (TSE) safety of
      therapeutics of biological origin (biologicals) is greatly influenced by the
      nature and degree of variability of the source material and by the mode of
      purification. Plasma-derived and recombinant DNA products currently have good
      viral safety records, but challenges remain. In general, large enveloped viruses
      are easier to remove from biologicals than small 'naked' viruses. Monoclonal
      antibodies and recombinant DNA biopharmaceuticals are derived from relatively
      homogeneous source materials and purified by multistep schemes that are robust
      and amenable to scientific analysis and engineering improvement. Viral clearance
      is more challenging for blood and cell products, as they are complex and labile.
      Source selection (e.g. country of origin, deferral for CJD risk factors)
      currently occupies the front line for ensuring that biologicals are free of TSE
      agents, but robust methods for their clearance from products are under
      development.

PMID- 16095900
TI  - Synergistic use of adult and embryonic stem cells to study human hematopoiesis.
AB  - Embryonic stem cells (ESCs) and adult stem cells both provide important resources
      to define the mechanisms of hematopoietic cell development. To date, studies that
      utilize hematopoietic stem cells (HSCs) isolated from sites such as bone marrow
      or umbilical cord blood have been the primary means to identify molecular and
      phenotypic characteristics of blood cell populations able to mediate long-term
      hematopoietic engraftment. Although these HSCs are very useful clinically, they
      are difficult to expand in culture. Now, basic research on human ESCs provides
      opportunities for novel investigations into the mechanisms of HSC self-renewal.
      Eventually, the long history of basic and clinical research with adult
      hematopoietic cell transplantation could translate to establish human ESCs as a
      suitable alternative starting cell source for clinical hematopoietic
      reconstitution.

PMID- 16095901
TI  - Structural and functional features of transcription factors controlling the
      circadian clock.
AB  - Most organisms adapt the timing of their physiology to the cyclic changes of the
      environment with the use of intrinsic time-keeping systems called circadian
      clocks. Central features of the molecular clock mechanism are transcription- and
      translation-based negative feedback loops: clock genes and their products
      interact to generate oscillation of specific transcripts and proteins, and,
      ultimately, circadian rhythmicity and behavior. Various transcription factors
      constitute the molecular clock, and the signal transduction cascades governing
      their function appear to be crucial for the fine-tuning of the circadian cycle.

PMID- 16095902
TI  - Something about SUMO inhibits transcription.
AB  - Many proteins that are important for regulated gene expression--including
      promoter-specific transcription factors, cofactors and chromatin-modifying
      enzymes--have been found to be reversibly modified by the small ubiquitin-related
      modifier, SUMO. Post-translational modification by SUMO has diverse effects on
      substrate activity, but, in most cases described to date, SUMOylation of
      transcriptional regulators correlates with inhibition of transcription. Recent
      studies provide new insights into the mechanisms by which SUMOylation regulates
      transcription and suggest that one consequence of SUMOylation is to promote the
      interaction of transcription factors with co-repressors. Histone deacetylase co
      repressors have been found to function as substrates, effectors, and regulators
      of SUMOylation, suggesting that complex crosstalk between acetylation and
      SUMOylation is important for gene regulation.

PMID- 16095903
TI  - Lime treatment of keratinous materials for the generation of highly digestible
      animal feed: 2. Animal hair.
AB  - Air-dried cow hair was treated using Ca(OH)(2) (insoluble in water but dissolved
      during reaction) at 100 degrees C. To obtain a liquid product rich in amino
      acids, a well-insulated, stirred reactor was used to perform the hydrolysis
      process for different time periods. High lime loadings and a long treatment
      period convert 70% of cow hair to soluble amino acids and polypeptides. Protein
      solubilization varies with lime loading especially for the long-term treatment
      (t>12h) showing that the hydroxyl group is required as a catalyst for the
      hydrolysis reaction and that lime is consumed during the process; as a
      consequence lower lime loading generate lower conversions. A very perceptible
      ammonia odor in the soluble product suggests amino acid degradation. Arginine,
      threonine, and serine are the more susceptible amino acids under alkaline
      hydrolysis. The amino acid composition of the solubilized product compares poorly
      with the essential amino acid requirements for various monogastric domestic
      animals, but it has value as ruminant feed.

PMID- 16095904
TI  - Do the histologic features and results of breast cancer biomarker studies differ
      between core biopsy and surgical excision specimens?
AB  - Core biopsies are commonly used in the diagnosis of breast cancer and often are
      the only sample for providing prognostic and predictive markers prior to
      neoadjuvant chemotherapy. We retrospectively studied 87 patients with breast
      cancer to compare the concordance rates for tumor type, grade, estrogen
      receptor/progesterone receptor (ER/PR), p53 status and Her2/neu by
      immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) between
      core and excisional biopsy specimens. The histologic type of cancer had a 100%
      concordance rate between core and excisional biopsy specimens. The concordance
      rate of modified Bloom-Richardson score between core and excisional biopsy
      specimens was 77%, ER was 95%, PR was 89%, and p53 was 86%. The concordance rate
      for Her2/neu by IHC was 96% and that for FISH was 100% between the core and
      excisional biopsy specimens. Although breast cancer may have heterogeneous
      histological and immunohistochemical findings, our study shows that relatively
      high concordance rates can be obtained when comparing core and excisional biopsy
      specimens.

PMID- 16095905
TI  - Spatiotemporal gait deviations in a virtual reality environment.
AB  - Previous research suggests that postural sway in standing increases in virtual
      reality (VR) environments. This study was conducted to examine whether gait
      instability is prevalent when people walk in a VR environment. Ten healthy adults
      participated in the study. Subjects walked on a treadmill in a VR environment and
      a non-VR environment at each of three walking speeds: 0.9, 1.1, and 1.3 m/s. In
      the VR environment, an endless corridor with colored vertical stripes comprising
      the walls was projected onto a hemispherical screen placed in front of the
      treadmill. The speed of the moving corridor image was matched to the speed of the
      treadmill to create the illusion that subjects were walking through the endless
      corridor. Spatiotemporal data during gait were collected with an instrumented
      treadmill housing two piezoelectric force platforms. Gait parameters reflective
      of gait instability (stride length, step width, variability in stride velocity,
      and variability in step width) were compared between the VR and non-VR
      environments. Subjects walked in the VR environment with reduced stride lengths
      (p = 0.001), increased step widths (p = 0.001), and with increased variability in
      stride velocity (p < 0.001) and step width (p = 0.002). The gait deviations
      suggest that walking in a VR environment may induce gait instability in healthy
      subjects.

PMID- 16095906
TI  - The photoionization-reduced energy in LSC.
AB  - The atomic rearrangement cascade that follows the electron-capture decay process
      in low-Z radionuclides involves X-rays which have high photoelectric interaction
      probabilities. When the K-shell binding energy of the ionized atom (e.g.,
      hydrogen) is significantly lower than the energy of the X-ray photon, the
      detector response to a photon-equivalent energy electron and the whole
      photoionization process are very similar. This is not the case when the
      scintillator cocktail contains larger atoms (e.g., oxygen and phosphorus in
      Ultima Gold). For larger Z atoms, the reduced energy of the whole photoionization
      process is less than the reduced energy of the interacting photon due to the
      nonlinear effects of ionization quenching. This paper shows the convenience of
      including a more detailed simulation of the photoionization process in the atomic
      rearrangement detection model for electron-capture nuclides such as (55)Fe,
      (51)Cr and (54)Mn. The need for more elaborate atomic rearrangement models is a
      consequence of the analysis of (125)I data.

PMID- 16095907
TI  - Focal not widespread grafts induce novel dyskinetic behavior in parkinsonian
      rats.
AB  - Dyskinesias are a common consequence of dopaminergic therapy in patients with
      Parkinson's disease. Little is known about the influence of cellular replacement
      strategies upon drug-induced dyskinesias. In the current study, we employed
      parkinsonian rats to test whether the distribution of dopamine neuron grafts
      could differentially alter striatal circuitry and levodopa-induced dyskinesias.
      Specifically, we compared behavioral and neurochemical consequences of dopamine
      reinnervation restricted to a focal region of the striatum to innervation
      encompassing the majority of the striatum by distributing the same number of
      cells into single locus or multiple locations. Both the single-site and
      widespread grafts reduced pregraft dyskinesias and normalized FosB/DeltaFosB in
      the dorsal two-thirds of the lateral striatum. However, single-site DA graft
      recipients developed a robust, novel forelimb-facial stereotypy and upregulated
      FosB/DeltaFosB expression in the ventrolateral striatum, an area associated with
      movements of tongue and forelimbs. The onset of forelimb-facial stereotypy
      correlated with measures of increased graft function.

PMID- 16095908
TI  - Purification and cloning of two high molecular mass isoforms of peanut seed
      oleosin encoded by cDNAs of equal sizes.
AB  - Oleosins are small plant proteins characterized by a long hydrophobic core
      flanked by amphipathic N- and C-terminal domains, which act as emulsifiers for
      the storage of lipids in seeds. They have been sequenced in a number of oilseeds
      important for the food industry but not in peanuts. We purified the major isoform
      of peanut oleosin by preparative electrophoresis with continuous elution, in
      sufficient amounts to raise specific antibodies, perform circular dichroism and N
      sequence tryptic fragments. The structure of the purified oleosin was dominated
      by alpha-helix that may be assigned to the SDS-resistant central hydrophobic
      stretch. A two-step RT-PCR strategy was developed to determine the cDNA sequence
      of this oleosin. Two cDNA variants of equal sizes encoding for isoforms of 176
      amino acids each were identified. The isoforms differed by seven amino acids
      mainly located in the N- and C-terminal domains. The corresponding mRNAs were
      estimated at 0.9 kb by Northern blot and were transcribed from genes without
      introns. Immunoprecipitation of the in vitro-translated peanut oleosin labeled
      with [14C]leucine or [35S]methionine produced the full-length protein (17 kDa)
      and a 6-kDa peptide corresponding to the N/C-terminal domains. This peptide was
      able to form SDS-PAGE stable oligomers by interacting with the full-length
      protein. A similar peptide was released after [125I]iodination of the purified
      oleosin that generated intermediate-sized oligomers also visible by Western blot
      on a crude oleosin extract. Oligomers reflect the natural ability of oleosins to
      strongly interact with each other via not only their central domains but also
      their N- and C-terminal domains.

PMID- 16095909
TI  - Generation of biologically active interleukin-1beta by meprin B.
AB  - Interleukin-1beta (IL-1beta) is a proinflammatory cytokine that is synthesized as
      an inactive precursor molecule that must be proteolytically processed to generate
      the biologically active form. Maturation of the precursor is primarily performed
      by caspase-1, an intracellular cysteine protease; however, processing by other
      proteases has been described. Meprins are cell surface and secreted
      metalloproteases expressed by renal and intestinal brush-border membranes,
      leukocytes, and cancer cells. In this study we show that purified recombinant
      meprin B can process the interleukin-1beta precursor to a biologically active
      form. Amino-terminal sequencing and mass spectrometry analysis of the product of
      digestion by activated meprin B determined that proteolytic cleavage resulted in
      an additional six amino acids relative to the site utilized by caspase-1. The
      biological activity of the meprin B-cleaved cytokine was confirmed by measuring
      the proliferative response of helper T-cells. These results suggest that meprin
      may play an important role in activation of this proinflammatory cytokine in
      various pathophysiological conditions.

PMID- 16095910
TI  - PAR-2 activation in intestinal epithelial cells potentiates interleukin-1beta
      induced chemokine secretion via MAP kinase signaling pathways.
AB  - Intestinal epithelial cells can be induced to secrete the chemokine interleukin
      (IL)-8 during inflammation. The PAR-2 receptor is believed to play a
      proinflammatory role and is expressed in gut epithelial cells. The aim was to
      investigate PAR-2 signaling in Caco-2 intestinal epithelial cells, with respect
      to chemokine secretion. Activation of PAR-2 by high concentrations of the
      synthetic activating peptide (SLIGKV) did not induce secretion of IL-8, in
      contrast to stimulation with IL-1beta. However, upon simultaneous treatment with
      activating peptide and IL-1beta, a potentiating effect of PAR-2 stimulation was
      seen, resulting in a fivefold increase of IL-8. Available data suggest that NF
      kappaB activation is required for IL-8 gene expression. Unlike IL-1beta, PAR-2
      stimulation did not activate NF-kappaB, which may explain the lack of IL-8
      expression. However, PAR-2 stimulation led to rapid phosphorylation of two MAP
      kinases, p38 MAPK and ERK1/2. ERK1/2 is known to activate the transcription
      factor AP-1, also involved in upregulation of IL-8 gene transcription. Inhibition
      of p38 MAPK led to decreased IL-8 following stimulation with IL-1beta and/or
      activating peptide. These results suggest that maximal IL-8 expression requires
      coordination of several signaling pathways. Thus, identifying antagonists to the
      PAR-2 receptor may be beneficial by inhibiting potentiation of a proinflammatory
      response, through inhibition of p38 and ERK MAP kinases.

PMID- 16095911
TI  - Ion funnels for the masses: experiments and simulations with a simplified ion
      funnel.
AB  - A modified ion funnel is described. Counterintuitively, increased spacing between
      electrodes results in enhanced "focusing" of the ions through the funnel.
      Consequently, the internal diameter (i.d.) of the funnel need not decrease to the
      conductance limit (as in previous designs). A simple dc-only lens, which also
      serves as the conductance limit, combined with the natural flow of gas is used to
      extract the ions from the funnel. Ions with mass to charge ratios varying between
      75 and 3000 m/z are passed through the funnel with no apparent discrimination.
      The funnel can be operated under mild conditions that preserve weakly bound
      noncovalent complexes. After testing several designs, a thin closely spaced dc
      lens was found to be the best solution for extracting ions. A simple method for
      simulating ion trajectories at nonzero pressures based on ion mobility and
      explicit diffusion is described. This theoretical approach was used to design and
      calculate ion trajectories for the modified funnel presented here. Finally, the
      increased spacing between electrodes in the current funnel significantly relaxes
      machining constraints, reduces cost, and enhances ease of use versus previous
      funnel designs.

PMID- 16095913
TI  - Efficiency of nano-electrospray ionization.
AB  - The efficiency of nano-electrospray ionization, defined as the flux of ions
      reaching the detector of a triple-quadrupole mass spectrometer divided by the
      flux of analyte ions leaving the needle, has been measured in a series of
      controlled experiments with dodecyltrimethyl ammonium (DDTMA) bromide, myoglobin,
      Glu- [1]-fibrinopeptide, and gramicidin S. By varying the flow rate from each
      needle, the optimum efficiency was determined. In general, the efficiency
      increased as the flow rate decreased. For DDTMA, efficiencies of up to 12% were
      measured, although efficiencies of approximately 1% were more common. Ion current
      measurements indicated efficient transfer of ions from the needle through to the
      detector. Significant needle-to-needle variations in efficiency were encountered
      and attributed to variations in ion-generation efficiency.

PMID- 16095912
TI  - MALDI-MS imaging of features smaller than the size of the laser beam.
AB  - The feasibility of matrix-assisted laser desorption/ionization mass spectrometry
      (MALDI-MS) imaging of features smaller than the laser beam size has been
      demonstrated. The method involves the complete ablation of the MALDI matrix
      coating the sample at each sample position and moving the sample target a
      distance less than the diameter of the laser beam before repeating the process.
      In the limit of complete sample ablation, acquiring signal from adjacent
      positions spaced by distances smaller than the sample probe enhances image
      resolution as the measured analyte signal only arises from the overlap of the
      laser beam size and the non-ablated sample surface. Image acquisition of features
      smaller than the laser beam size has been demonstrated with peptide standards
      deposited on electron microscopy calibration grids and with neuropeptides
      originating from single cells. The presented MS imaging technique enables
      approximately 25 microm imaging spatial resolution using commercial MALDI mass
      spectrometers having irregular laser beam sizes of several hundred micron
      diameters. With appropriate sampling, the size of the laser beam is not a strict
      barrier to the attainable MALDI-MS imaging resolution.

PMID- 16095914
TI  - Direct interaction of N-ethylmaleimide-sensitive factor with GABA(A) receptor
      beta subunits.
AB  - GABA(A) receptors mediate most of the fast inhibitory neurotransmission in the
      brain, and are believed to be composed mainly of alpha, beta, and gamma subunits.
      It has been shown that GABA(A) receptors interact with a number of binding
      partners that act to regulate both receptor function and cell surface stability.
      Here, we reveal that GABA(A) receptors interact directly with N-ethylmaleimide
      sensitive factor (NSF), a critical regulator of vesicular dependent protein
      trafficking, as measured by in vitro protein binding and co-immunoprecipitation
      assays. In addition, we established that NSF interacts with residues 395-415 of
      the receptor beta subunits and co-localizes with GABA(A) receptors in hippocampal
      neurons. We also established that NSF can regulate GABA(A) receptor cell surface
      expression depending upon residues 395-415 in the beta3 subunit. Together, our
      results suggest an important role for NSF activity in regulating the cell surface
      stability of GABA(A) receptors.

PMID- 16095915
TI  - Analysis of mRNAs that are enriched in the post-synaptic domain of the
      neuromuscular junction.
AB  - The identity of synaptically-enriched genes was investigated by comparing the
      abundance of various mRNAs in the synaptic and extra-synaptic regions of the same
      muscle fibers. The mRNAs for several known synaptic proteins were significantly
      elevated in the synaptic region when measured by real-time PCR. The synaptic
      mRNAs were then further analyzed using microarrays and real-time PCR to identify
      putative regulators of the neuromuscular junction (NMJ). MRF4 was the only member
      of the MyoD family that was concentrated at the mature NMJ, suggesting that it
      may have a unique role in the maintenance of post-synaptic specialization. Three
      potential regulators of the NMJ were identified and confirmed by real-time PCR:
      glia maturation factor gamma was concentrated at the NMJ whereas Unr protein and
      protein tyrosine phosphatase were repressed synaptically. The identification of
      synaptically-repressed genes may indicate that synaptic specialization is created
      by a combination of positive and negative signals.

PMID- 16095916
TI  - Using quantitative imaging microscopy to define the target substrate
      specificities of histone post-translational-modifying enzymes.
AB  - Until recently, identifying the specificities of enzymes that post
      translationally modify core histones was performed in vitro using synthetic
      peptides, purified mononucleosomes or short nucleosome arrays. Unfortunately, the
      variable results obtained for identical enzymes are often dependent on the in
      vitro conditions employed. These results are consistent with the conclusion that
      the manner in which histone tails are presented to the modifying enzymes
      dramatically affects specificity. Because traditional in vitro biochemical
      approaches do not accurately recapitulate higher-order chromatin structure or
      consider the influences that additional chromatin binding proteins may have on
      determining the specificity of modifying enzymes, the development of new and
      innovative approaches is warranted. Here, we describe a novel in situ microscopy
      approach that accurately assesses enzyme substrate specificities through single
      cell measurements performed under physiologically relevant conditions. This
      approach couples the spatial resolving power of microscopy with robust
      statistical analyses to determine the substrate specificities of transiently
      expressed enzymes using histone modification- and residue-specific antibodies.
      This methodology can also be applied to measuring changes in the abundance of
      histone modifications as cells traverse the cell cycle.

PMID- 16095917
TI  - Expression, purification, and biochemical characterization of the intron-encoded
      endonuclease, I-CreII.
AB  - The ORF of the Cr.psbA4 intron of Chlamydomonas reinhardtii mediates efficient
      intron homing, and contains an H-N-H and possibly a GIY-YIG motif. The ORF was
      over-expressed in Escherichia coli without non-native amino acids, but was mostly
      insoluble. However, co-over-expression of E. coli chaperonins GroEL/GroES
      solubilized approximately 50% of the protein, which was purified by ion-exchange
      and heparin-affinity chromatography. Biochemical characterization showed that the
      protein is a double-strand-specific endonuclease that cleaves fused psbA exon 4
      exon 5 DNA, and was named I-CreII. I-CreII has a relatively relaxed divalent
      metal ion requirement (Mg(2+), Mn(2+), Ca(2+), and Fe(2+) supported cleavage), is
      insensitive to salt <350 mM, and is stabilized by DNA. Cleavage of target DNA
      occurs close (4 nt on the top strand) to the intron-insertion site, and leaves 2
      nt 3'-OH overhangs, similar to GIY-YIG endonucleases. The boundaries of the
      recognition sequence span approximately 30 bp, and encompass the cleavage and
      intron-insertion sites. Cleavage of heterologous psbA DNAs indicates the enzyme
      can tolerate multiple, but not all, substitutions in the recognition site. This
      work will facilitate further study of this novel endonuclease, which may also
      find use in site-specific manipulation of chloroplast DNA.

PMID- 16095918
TI  - Structurally unique recombinant Kazal-type proteinase inhibitor retains activity
      when terminally extended and glycosylated.
AB  - Recombinant derivatives of the Kazal-type serine proteinase inhibitor GmSPI2 (36
      amino acid residues), which is a component of insect silk, were prepared in the
      expression vector Pichia pastoris. The rhSPI2 had a C-terminal hexahistidine tag
      attached to the GmSPI2 sequence, rtSPI2 was extended with GluAlaAla at the N
      terminus, and rfSPI2 included this N-terminal extension and a C-terminal tail of
      22 residues (myc epitope and hexahistidine). A portion of the secreted rfSI2 was
      O-glycosylated with a trimannosyl or hexamannosyl. The native inhibitor was
      active slightly on trypsin and highly on subtilisin and proteinase K. The
      extended C-terminus in rhSPI2 and rfSPI2 enhanced activity on the two latter
      enzymes and rendered rfSPI2 active on elastase and pronase, but abolished the
      inhibition of trypsin. The glycosylation of rfSPI2 reduced its inhibitory
      activity to a level comparable with the native inhibitor. The rtSPI2 with
      tripeptide extension at the N-terminus and no C-terminal modification was clearly
      less active than the native inhibitor. None of the tested compounds inhibited
      alpha-chymotrypsin and the non-serine proteinases.

PMID- 16095919
TI  - Solubilization, purification, and mass spectrometry analysis of the human mu
      opioid receptor expressed in Pichia pastoris.
AB  - The human mu-opioid receptor was expressed in Pichia pastoris with or without
      EGFP at the N-terminal end. Expression yields of the recombinant proteins reached
      several tens of milligram of receptor per liter of culture medium in shacked
      flasks. Pharmacological studies using specific ligands demonstrated a typical
      opioid profile for the HuMOR-c-myc-his-tag construct, whereas the GFP-HuMOR-c-myc
      his-tag receptor was unable to bind opioid drugs. The hexahistidine epitope
      tagged receptors were purified by immobilized-nickel affinity chromatography. The
      identity of the purified mu-opioid receptor proteins was confirmed by Western
      blot and mass spectrometry analysis. In conclusion, the expression,
      solubilization, and purification strategies described herein allow to isolate
      very high quantities of purified receptor, up to 12 mg/L.

PMID- 16095920
TI  - A special role for numbers in working memory? An fMRI study.
AB  - Although numbers carry averbal semantics (i.e., magnitude), they are often
      utilized in verbal Working Memory (vWM) tasks. However, vWM is thought to rely on
      a purely phonological code. Here, we tested the influence of (a) averbal
      semantics and (b) different tasks on performance in a vWM context by examining
      stimulus and task-specific variation of activity in the horizontal parts of the
      intraparietal sulcus (hIPS). The hIPS has previously been shown to subserve
      magnitude processing modulated by (a) specific stimuli and (b) specific tasks.
      Two variants of an n-back paradigm (comparison and identity match tasks)
      utilizing letters and numbers as stimulus material at different levels of vWM
      load were administered in 16 participants. Behavioral and functional imaging data
      reveal stimulus-specific modulation of activity in the hIPS suggesting a semantic
      influence of numbers. In the identity match task, numbers induced additional hIPS
      activation compared to letters while letters never induced additional hIPS
      activation when compared to numbers. Letters as compared to numbers only induced
      additional hIPS activation in the comparison task. These results question the
      assumption of a purely phonological code in vWM because hIPS activation
      subserving magnitude processing is modulated by stimulus semantics and task
      demands.

PMID- 16095921
TI  - Changes in BOLD and ADC weighted imaging in acute hypoxia during sea-level and
      altitude adapted states.
AB  - Acute normobaric hypoxia as well as longstanding hypobaric hypoxia induce
      pronounced physiological changes and may eventually lead to impairment of
      cerebral function. The aim of the present study is to investigate the effect of
      hypoxia on the cerebral activation response as well as to explore possible
      structural changes as measured by diffusion weighted imaging. Eleven healthy sea
      level residents were studied after 5 weeks of adaptation to high altitude
      conditions at Chacaltaya, Bolivia (5260 m). The subjects were studied immediately
      after return to sea-level in hypoxic and normoxic conditions, and the
      examinations repeated 6 months later after re-adaptation to sea-level conditions.
      The BOLD response, measured at 1.5 T, was severely reduced during acute hypoxia
      both in the altitude and sea-level adapted states (50% reduction during an
      average S(a)O(2) of 75%). On average, the BOLD response magnitude was 23% lower
      in altitude than sea-level adaptation in the normoxic condition, but in the
      hypoxic condition, no significant differences were found. A small but
      statistically significant decrease in the apparent diffusion coefficient (ADC)
      was seen in some brain regions during acute hypoxia, whereas ADC was slightly
      elevated in high altitude as compared to sea-level adaptation. It is concluded
      that hypoxia significantly diminishes the BOLD response, and the mechanisms
      underlying this finding are discussed. Furthermore, altitude adaptation may
      influence both the magnitude of the activation-related response, as well as micro
      structural features.

PMID- 16095922
TI  - Event-related optical imaging reveals the temporal dynamics of right temporal and
      frontal cortex activation in pre-attentive change detection.
AB  - The mismatch negativity (MMN) is a pre-attentive brain response to auditory
      environmental change. Temporal and frontal cortex generators of pre-attentive
      change detection have been proposed based on source localization of event-related
      potentials (ERP), positron emission tomography (PET), and functional magnetic
      resonance imaging (fMRI) studies. The temporal cortex generators are believed to
      underlie change detection, whereas the frontal cortex generators are thought to
      subserve reorientation of attention in response to change. The present study used
      the event-related optical signal (EROS), an imaging technique that is sensitive
      to activity related changes in the light scattering properties of neurons, to
      investigate the pre-attentive brain response to stimulus omissions. The stimulus
      train comprised 10 ms tone pips presented with a stimulus onset asynchrony (SOA)
      of 84 ms. Occasional tone omissions elicited a significant increase in right
      superior temporal gyrus (STG) activity 140 ms after the omitted stimulus,
      followed 60 ms later by right inferior frontal gyrus (IFG) activity. This result
      provides support for a temporal-frontal cortical network that underlies pre
      attentive change detection.

PMID- 16095923
TI  - In vivo flow territory mapping of major brain feeding arteries.
AB  - The ability to visualize the perfusion territories of major feeding arteries to
      the brain is important for many clinical applications. Since the work of Duret in
      1874 on vascularization of the brain, many textbooks and atlases have shown
      schematic drawings of the supply areas of the major cerebral arteries. Recent
      postmortem studies demonstrated that the variability of the cerebral vascular
      territories is significantly greater than previously assumed. The aim of the
      present study was to investigate in vivo, the variability of flow territories of
      major brain feeding arteries. Flow territory mapping of the anterior (internal
      carotid arteries) and posterior (basilar artery) circulation was performed in 115
      (58 +/- 9 years of age) subjects with selective arterial spin labeling MRI. Flow
      territory maps for the entire population indicated significant variation in flow
      territories. However, when the subjects are further categorized into groups with
      a complete circle of Willis, with a missing A1 segment and with a unilateral or
      bilateral fetal-type posterior cerebral artery, the results showed considerably
      lower variation within groups. It is therefore concluded that, the variation
      observed from the entire population is mainly caused by anatomical variants of
      the circle of Willis. To relate focal brain lesions to underlying flow
      territories in individual cases, knowledge of the anatomy of the circle of Willis
      is essential.

PMID- 16095924
TI  - Evolution and phylogeography of Halimeda section Halimeda (Bryopsidales,
      Chlorophyta).
AB  - Nuclear ribosomal and plastid DNA sequences of specimens belonging to section
      Halimeda of the pantropical green seaweed genus Halimeda show that the group
      under scrutiny contains many more genetically delineable species than those
      recognized by classical taxonomy. Discordances between phylograms inferred from
      nuclear and plastid DNA sequences suggest that reticulate evolution has been
      involved in speciation within the clade. Nonetheless, our data do not allow
      ruling out certain alternative explanations for the discordances. Several pseudo
      cryptic species are restricted to the margins of the generic distribution range.
      In a clade of H. cuneata sibling species from widely separated subtropical
      localities in the Indian Ocean, the South African sibling branches off first,
      leaving the Arabian and West Australian species as closest relatives. We
      hypothesize that geographic isolation of the siblings may have taken place
      following Pleistocene or Pliocene periods of climatic cooling during which
      subtropical species occupied larger distribution ranges. A more basal separation
      of Atlantic, Indo-Pacific, and Mediterranean species indicates vicariance. The
      alternative events that could have caused this vicariance are discussed.

PMID- 16095925
TI  - Molecular phylogeny and evolution of Caricaceae based on rDNA internal
      transcribed spacers and chloroplast sequence data.
AB  - This study focused on clarifying phylogenetic relationships and evolution within
      Caricaceae. Our phylogenetic analysis based on nucleotide sequences from the ITS
      of the ribosomal DNA and three chloroplast fragments (matK, trnL-trnF, and psbA
      trnH) included 29 taxa belonging to five genera: the neotropical genera Carica,
      Vasconcellea, Jarilla, and Jacaratia and the equatorial African genus
      Cylicomorpha. Having a relatively low mutation rate, matK, and trnL-trnF were
      used for estimating relationships at the generic level, while intrageneric
      evolution within Vasconcellea was studied with the more variable ITS and psbA
      trnH sequences. Gaps, coded as binary characters, were added to the sequence
      alignments before performing Maximum Parsimony and Maximum Likelihood analyses.
      Monophyly of Caricaceae as well as phylogenetic distance between Carica and
      Vasconcellea species, previously belonging to the same genus, and monophyly of
      the resurrected genus Vasconcellea were emphasized. Within Vasconcellea, the
      largest genus of this family, two well-confirmed evolutionary lineages could be
      discerned: (1) V.xheilbornii, V. weberbaueri, V. stipulata, and V. parviflora and
      (2) a clade holding all other taxa of the genus. Incongruence between nuclear ITS
      and chloroplast psbA-trnH datasets, shown to be significantly caused by some taxa
      of the genus Vasconcellea, indicated that reticulate events in this genus might
      be more frequent than previously suspected. Moreover, intra-individual ITS
      sequence heterogeneity provided further evidence for the hybrid or introgressed
      origin of different taxa and one presumed hybrid belonging to this genus.

PMID- 16095926
TI  - Epilepsy & depression: the effects of comorbidity on hippocampal volume--a pilot
      study.
AB  - Hippocampal sclerosis (HS) is one of the most common pathologies in medically
      intractable temporal lobe intractable epilepsy. Significant hippocampal volume
      loss has also been found in patients with chronic depression. Depression is
      common in chronic epilepsy populations, but the effects of this comorbidity on
      hippocampal volume are unknown. We examined the hippocampal volumes of 87
      patients (n=31 right hippocampal sclerosis, RHS; n=56 left hippocampal sclerosis,
      LHS). Each subject completed the Hospital Anxiety and Depression Scale (HADS). In
      the group as a whole, 13 subjects (15%) recorded moderate or severe levels of
      depression. Depression was more common in the LHS group with 1 in 5 scoring in
      the moderate or severe range on the HADS (n=11). Depression scores were not
      significantly correlated with quantitative measures of hippocampal volume in the
      LHS group. However, higher degrees of hippocampal symmetry were associated with
      higher levels of depression in the RHS group. This suggests that the left
      hippocampus may be smaller in depressed patients with RHS, although our numbers
      were too small to confirm this statistically. Our results suggest that the
      depression may influence left hippocampal volume in patients with right
      hippocampal sclerosis. We conclude that the neuroradiological characteristics of
      patients with epilepsy and chronic depression deserve further examination.

PMID- 16095927
TI  - Chronic levetiracetam treatment early in life decreases epileptiform events in
      young GAERS, but does not prevent the expression of spike and wave discharges
      during adulthood.
AB  - PURPOSE: In Genetic Absence Epilepsy Rats from Strasbourg (GAERS), age-related
      absence seizures start to appear from postnatal day (PN) 30 concomitant with
      'spike and wave discharges' (SWDs) appearing on cortical EEG recordings. The aim
      of this study was to investigate the effect of early chronic levetiracetam (LEV)
      treatment on the development of SWDs in young and adult GAERS. METHODS: From PN
      23 until PN 60, LEV (54 mg/kg, i.p.) was administered once daily to GAERS (n=8),
      while control GAERS (n=7) received saline (0.9% NaCl, i.p.). All animals were
      implanted with four epidural EEG electrodes at PN 51. EEG was recorded for 3h
      daily, during the last 4 days of the treatment (PN 57-PN 60) and during 4
      additional days after treatment had been terminated (PN 61-PN 64). The animals
      were monitored again at the age of 4 months (PN 120-PN 124), about 2 months after
      the last administration of LEV. RESULTS: During treatment, epileptiform events in
      the LEV group were significantly reduced (62%, P<0.05) in comparison with the
      control group. During the following 4 days, epileptiform events were reduced in
      the LEV group, with an average difference of 53% (P=0.064). Once the animals had
      reached adult age, there was no difference in epileptiform events between the LEV
      group and controls. CONCLUSION: In this study, chronic LEV administration induced
      a reduction in epileptiform events in young GAERS. This effect persisted to some
      extent after treatment cessation (PN 61-PN 64), which might indicate a slowing
      down of epileptogenic processes. However, at the age of 4 months all animals
      revealed a similar expression of epileptiform discharges.

PMID- 16095928
TI  - Tissue remodeling in Guinea pig lateral prostate at different ages after
      estradiol treatment.
AB  - Estrogen seems to have an essential role in the fibromuscular growth
      characteristic of benign prostatic hyperplasia (BPH). This paper describes the
      effects of chronic estradiol treatment on Guinea pig prostatic stroma at
      different ages. Tissues from experimental animals were studied by histological
      and histochemical procedures, morphometric-stereological analysis and
      transmission electron microscopy (TEM). Marked fibromuscular hypertrophy was
      observed after estradiol treatment in animals of pre-pubertal and adult ages.
      Increases in the density and thickness of the collagen and elastic fibers were
      observed by histochemistry. TEM revealed wide distributions of collagen fibrils
      and large elastic fibers adjacent to the epithelial basal lamina and between the
      stromal cells, establishing contacts between them. These results indicate that
      the Guinea pig prostate simulates the stromal modifications observed in BPH in
      some aged animals after estrogen treatment at different ages, making it a good
      model for this disease.

PMID- 16095930
TI  - Fibrin clots keep non-adhering living cells in place on glass for perfusion or
      fixation.
AB  - We describe a method to hold living cells in place that ordinarily do not adhere
      to glass coverslips. The method, developed for insect spermatocytes but with
      application to other cell types, consists of embedding cells in a fibrin clot
      that forms after the enzyme thrombin cleaves the blood protein fibrinogen. The
      method permits continuous observation of living cells as they are treated with
      and recover from drug or other treatments: when held in the clot the living cells
      remain in place and keep their shapes when perfused with drugs that ordinarily
      cause drastic shape changes, and they remain in place and keep their shapes
      through lysis/fixation procedures. We describe how to place live cells in a
      fibrin clot and how subsequently to perfuse them.

PMID- 16095929
TI  - Effects of triple antioxidant combination (vitamin E, vitamin C and alpha-lipoic
      acid) with insulin on lipid and cholesterol levels and fatty acid composition of
      brain tissue in experimental diabetic and non-diabetic rats.
AB  - The aim of this research was to examine the effects of a triple antioxidant
      combination (vitamins E (VE) and C (VC) plus alpha-lipoic acid (LA)) on the total
      lipid and cholesterol levels and the fatty acid composition of brain tissues in
      experimental diabetic and non-diabetic rats. VE and LA were injected
      intraperitoneally (50 mg/kg) four times per week and VC was provided as a
      supplement dissolved in the drinking water (50 mg/kg). In addition, rats in the
      diabetes 1 and D+VELAVC groups were given daily by subcutaneous insulin
      injections (8 IU/kg), but no insulin was given to rats in the diabetes 2 group.
      The results indicate that the brain lipid levels in the D+VELAVC, diabetes 1 and
      diabetes 2 groups were higher than in the control group (P<0.01). Total lipid was
      also higher in the non-diabetic rats treated with LA and VC. Total cholesterol
      was higher in the diabetes 1 and diabetes 2 groups (P<0.05) than in controls.
      Cholesterol levels were similar in the D+VELAVC and LA groups but lower in the
      VC, VE and VELAVC groups of non-diabetic rats (P<0.05 and P<0.01). In respect of
      fatty acid composition, palmitic acid levels were lower in the diabetes 2 and non
      diabetic VE groups than the control group (P<0.05), but higher in the non
      diabetic LA group (P<0.05). Oleic acid (18:1 n-9) levels were lower in the
      diabetic and non-diabetic groups than the control group (P<0.01), but higher in
      the non-diabetic LA group. Arachidonic acid (20:4 n-6) levels were similar in the
      diabetes 1, D+VELAVC and control groups (P>0.05) but higher in the non-diabetic
      VE, VC, LA and VEVCLA groups (P<0.05) and lower in the diabetes 2 group (P<0.05).
      Docosahexaenoic acid (22:6 n-3) was elevated in the diabetes 2 and VEVCLA groups
      (P<0.01, P<0.05). In conclusion, the current study confirmed that treatment with
      a triple combination of VE, VC and LA protects the arachidonic acid level in the
      brains of diabetic and non-diabetic rats.

PMID- 16095931
TI  - Relative tolerance to upper- and lower-limb aerobic exercise in patients with
      peripheral arterial disease.
AB  - OBJECTIVES: To investigate the effects of peripheral arterial disease (PAD) on
      relative tolerance to upper- and lower-limb aerobic exercise. METHODS: Peak
      cardiorespiratory responses evoked by an incremental arm-cranking test (ACT) and
      an incremental leg-cranking test (LCT) were compared in patients with PAD (N=101;
      median age 69 year, range 50-85 years). Claudication distance (CD) and total
      distance before intolerable claudication pain (maximum walking distance: MWD)
      were also assessed during walking. RESULTS: Peak oxygen consumption (V O(2)) for
      the ACT was 94% of that measured for the LCT (1.01+/-0.03 versus 1.10+/-0.03lmin(
      1), respectively; P<0.001), but in a significant proportion of patients (35%;
      P<0.001), exceeded that recorded for the LCT. The ratio of upper- to lower-limb
      peak V O(2) was higher (0.98+/-0.04 compared to 0.98+/-0.05lmin(-1) and 1.00+/
      0.06 compared to 1.21+/-0.06lmin(-1); P<0.01), whereas walking performance (CD:
      94+/-14 versus 187+/-25 m, P<0.01; MWD: 227+/-20 versus 394+/-33 m, P<0.01) was
      lower for patients in the lowest ankle to brachial pressure index quartile
      compared to patients in the highest quartile, respectively. CONCLUSION: Upper
      limb aerobic conditioning could be a useful exercise stimulus for maintaining or
      improving cardiorespiratory function in patients with severe PAD as they have a
      greater relative upper-limb aerobic power.

PMID- 16095932
TI  - The association between raised coagulation factor levels and venous thrombo
      embolism.

PMID- 16095933
TI  - Molecular regulation of satellite cell function.
AB  - Quiescent satellite cells are responsible for the repair of post-natal skeletal
      muscle. These cells are easily identified by their unique morphology within
      skeletal muscle as well as by several recently elucidated molecular markers.
      Careful examination of the function of these markers has provided insight into
      the early events surrounding satellite cell specification and activation.
      However, the origin of these cells, as well as the mechanisms by which this
      population is maintained within the adult remain elusive. Furthermore, the
      ability of non-muscle derived stem cells and the potential multipotency of
      satellite cells have altered the traditional views of skeletal muscle
      regeneration.

PMID- 16095934
TI  - Survey of chronic pain in Europe: prevalence, impact on daily life, and
      treatment.
AB  - This large scale computer-assisted telephone survey was undertaken to explore the
      prevalence, severity, treatment and impact of chronic pain in 15 European
      countries and Israel. Screening interviews identified respondents aged 18 years
      with chronic pain for in-depth interviews. 19% of 46,394 respondents willing to
      participate (refusal rate 46%) had suffered pain for 6 months, had experienced
      pain in the last month and several times during the last week. Their pain
      intensity was 5 on a 10-point Numeric Rating Scale (NRS) (1 = no pain, 10 = worst
      pain imaginable) during last episode of pain. In-depth interviews with 4839
      respondents with chronic pain (about 300 per country) showed: 66% had moderate
      pain (NRS = 5-7), 34% had severe pain (NRS = 8-10), 46% had constant pain, 54%
      had intermittent pain. 59% had suffered with pain for two to 15 years, 21% had
      been diagnosed with depression because of their pain, 61% were less able or
      unable to work outside the home, 19% had lost their job and 13% had changed jobs
      because of their pain. 60% visited their doctor about their pain 2-9 times in the
      last six months. Only 2% were currently treated by a pain management specialist.
      One-third of the chronic pain sufferers were currently not being treated. Two
      thirds used non-medication treatments, e.g,. massage (30%), physical therapy
      (21%), acupuncture (13%). Almost half were taking non-prescription analgesics;
      'over the counter' (OTC) NSAIDs (55%), paracetamol (43%), weak opioids (13%). Two
      thirds were taking prescription medicines: NSAIDs (44%), weak opioids (23%),
      paracetamol (18%), COX-2 inhibitors (1-36%), and strong opioids (5%). Forty
      percent had inadequate management of their pain. Interesting differences between
      countries were observed, possibly reflecting differences in cultural background
      and local traditions in managing chronic pain. CONCLUSIONS: Chronic pain of
      moderate to severe intensity occurs in 19% of adult Europeans, seriously
      affecting the quality of their social and working lives. Very few were managed by
      pain specialists and nearly half received inadequate pain management. Although
      differences were observed between the 16 countries, we have documented that
      chronic pain is a major health care problem in Europe that needs to be taken more
      seriously.

PMID- 16095935
TI  - Fear of pain, not pain catastrophizing, predicts acute pain intensity, but
      neither factor predicts tolerance or blood pressure reactivity: an experimental
      investigation in pain-free individuals.
AB  - Previous studies of the Fear-Avoidance Model of Exaggerated Pain Perception have
      commonly included patients with chronic low back pain, making it difficult to
      determine which psychological factors led to the development of an "exaggerated
      pain perception". This study investigated the validity of the Fear-Avoidance
      Model of Exaggerated Pain Perception by considering the influence of fear of pain
      and pain catastrophizing on acute pain perception, after considering sex and
      anxiety. Thirty-two males and 34 females completed the State-Trait Anxiety
      Inventory, the Fear of Pain Questionnaire, and the Coping Strategies
      Questionnaire. Subjects underwent a cold pressor procedure and tolerance, pain
      intensity, and blood pressure reactivity were measured. Sex, anxiety, fear of
      pain, and pain catastrophizing were simultaneously entered into separate multiple
      regression models to predict different components of pain perception. Tolerance
      was not predicted by fear of pain, pain catastrophizing, or anxiety. Pain
      intensity at threshold and tolerance were significantly predicted by fear of
      pain, only. Blood pressure reactivity to pain was significantly predicted by
      anxiety, only. These results suggest that fear of pain may have a stronger
      influence on acute pain intensity when compared to pain catastrophizing, while
      neither of the factors predicted tolerance or blood pressure reactivity.

PMID- 16095936
TI  - Dutch translation of the Fear of Pain Questionnaire: factor structure,
      reliability and validity.
AB  - BACKGROUND: The Fear of Pain Questionnaire (FPQ-III) is a 30-item self-report
      instrument measuring fear of a variety of pain-related stimuli. AIM: The present
      study was undertaken to develop a Dutch version of the FPQ-III, to assess the
      instrument's psychometric qualities, to examine the suggested factor structure,
      and to relate the FPQ-III to other general psychological constructs in order to
      assess its construct validity. METHOD: The questionnaire was translated following
      the forward-backward method. The final version was filled out by (n = 274)
      psychology freshmen. A random half of the subjects was re-tested after five
      weeks. RESULTS: Satisfactory psychometric qualities were obtained (average alpha
      = 0.90 and test-retest reliability = 0.71). Factor analysis supported the three
      factor structure and also the results concerning divergent and convergent
      validity show strong similarity with the results from other studies. CONCLUSIONS:
      The Dutch translation of the FPQ-III appears to be a valid equivalent of the
      original English version and does represent a unique construct.

PMID- 16095937
TI  - Metabolic response to feeding in the Chinese striped-necked turtle, Ocadia
      sinensis.
AB  - We measured oxygen consumption in juvenile Chinese striped-necked turtles (Ocadia
      sinensis) after they ingested food, either as a single meal or as double meals,
      to examine the influence of meal type and feeding frequency on specific dynamic
      action (SDA). Temporal variation in oxygen consumption after feeding was evident
      in the ingesting turtles but not in the unfed control turtles. In the single-meal
      experiment, the peak metabolic rate and the integrated SDA response (the whole
      energetic cost for the processes of digestion) both did not differ between
      turtles ingesting mealworms and shrimps when the influence of variation in
      ingested energy was removed, and the time to reach peak metabolic rate was not
      affected by meal type and the amount of food ingested. Turtles in the double-meal
      experiment ingested more energy and hence had a prolonged duration of SDA
      response than did those in the single-meal experiment, but the integrated SDA
      response did not differ between both experimental treatments when the influence
      of variation in ingested energy was removed. Our results show that meal type and
      feeding frequency have important consequences on the SDA response of juvenile O.
      sinensis. As the integrated SDA response remained remarkably constant either
      between turtles ingesting different food or between turtles ingesting the same
      food but at different frequencies when the influence of variation in ingested
      energy was removed, we therefore conclude that the energetic cost associated with
      ingestion is primarily determined by energy content of food ingested in juvenile
      O. sinensis.

PMID- 16095938
TI  - Functional analysis of 1440 Escherichia coli genes using the combination of knock
      out library and phenotype microarrays.
AB  - Escherichia coli is one of the best elucidated organisms. However, about 40% of
      E. coli genes have not been assigned to their function yet. We analyzed 1440
      single gene knock-out mutants using the GN2-MicroPlate, which permits assay of 95
      carbon-source utilizations simultaneously. In the knock-out library there are
      1044 of so called y-genes with no apparent function. The raw dataset was analyzed
      and genes were interrelated by the clustering method of the GeneSpring software.
      In the resulted dendrogram of genes, a group of genes with known and related
      function tended to be assembled into a cluster. Our clustering method would be
      useful for functional assignment of so called y-genes with no apparent function,
      since the resulted dendrogram could connect y-genes to phenotype and function of
      well-studied genes.

PMID- 16095939
TI  - Metabolic engineering of Clostridium acetobutylicum for the industrial production
      of 1,3-propanediol from glycerol.
AB  - Clostridium butyricum is to our knowledge the best natural 1,3-propanediol
      producer from glycerol and the only microorganism identified so far to use a
      coenzyme B12-independent glycerol dehydratase. However, to develop an economical
      process of 1,3-propanediol production, it would be necessary to improve the
      strain by a metabolic engineering approach. Unfortunately, no genetic tools are
      currently available for C. butyricum and all our efforts to develop them have
      been so far unsuccessful. To obtain a better "vitamin B12-free" biological
      process, we developed a metabolic engineering strategy with Clostridium
      acetobutylicum. The 1,3-propanediol pathway from C. butyricum was introduced on a
      plasmid in several mutants of C. acetobutylicum altered in product formation. The
      DG1(pSPD5) recombinant strain was the most efficient strain and was further
      characterized from a physiological and biotechnological point of view. Chemostat
      cultures of this strain grown on glucose alone produced only acids (acetate,
      butyrate and lactate) and a high level of hydrogen. In contrast, when glycerol
      was metabolized in chemostat culture, 1,3-propanediol became the major product,
      the specific rate of acid formation decreased and a very low level of hydrogen
      was observed. In a fed-batch culture, the DG1(pSPD5) strain was able to produce
      1,3-propanediol at a higher concentration (1104 mM) and productivity than the
      natural producer C. butyricum VPI 3266. Furthermore, this strain was also
      successfully used for very long term continuous production of 1,3-propanediol at
      high volumetric productivity (3 g L-1 h-1) and titer (788 mM).

PMID- 16095940
TI  - Epidemiology and clinical characteristics of classic Kaposi's sarcoma,
      seroprevalence, and variants of human herpesvirus 8 in South America: a critical
      review of an old disease.
AB  - OBJECTIVE: To review the current South American literature on classic Kaposi's
      sarcoma (KS) and human herpesvirus 8 (HHV-8), and point the way for studies that
      still need to be performed. MATERIALS AND METHODS: The authors performed an
      exhaustive search in LILACS, SCIELO and PUBMED databases for classic KS and HHV-8
      in South America. The relevant material was evaluated and reviewed. RESULTS: More
      than 250 cases have been reported with three big case series (Argentina, Colombia
      and Peru). The classic KS form seen in Colombia resembles the type of disease
      seen among African communities; the same unusual presentation with confluent
      exophytic nodules or eroded lesions has been noticed in Peru. Low rates of HHV-8
      antibodies have been found in blood donors from Chile, Argentina and Brazil (3%,
      4%, 2.8-7.4%, respectively); whereas high rates of HHV-8 antibodies have been
      found in Amerindians from Brazil and Ecuador. Five specimens from Argentina were
      subtyped: (three classic KS and two AIDS KS); the identified strains fell into
      subtypes A and C. AIDS-related KS specimens from Brazil and Venezuela were
      subtyped: (43 and nine respectively); analysis grouped them predominantly into
      subgroups A, B and C. A new HHV-8 subtype E was found endemic in Brazilian and
      Ecuadorian Amerindians. In French Guiana ten endemic KS and six AIDS-related KS
      specimens were subtyped; analysis grouped them predominantly into subgroups A, B
      and C. CONCLUSION: Classic KS in South America has a very similar clinical
      presentation but not the same as the classic KS variety described in the
      Mediterranean. Initial seroprevalence studies performed in the general population
      and in blood donors showed low seroprevalence of HHV-8, whereas high
      seroprevalence rates were seen in Amerindian population. The existing serological
      assays, nonetheless, need to be further refined, and new assays need to be
      developed. Finally, the key to understanding the precise molecular epidemiology
      and phylogenetic distribution of HHV-8 in South America would be to perform more
      subtyping of classic KS cases.

PMID- 16095941
TI  - Antibiotic treatment and the diagnosis of Streptococcus pneumoniae in lower
      respiratory tract infections in adults.
AB  - OBJECTIVE: To analyze the possible influence of antibiotic treatment on the
      results of different diagnostic tests for the diagnosis of lower respiratory
      tract infections with Streptococcus pneumoniae. MATERIAL AND METHODS: A
      prospective cohort of 159 unselected adult immunocompetent patients admitted to
      Silkeborg County Hospital in Denmark with community-acquired lower respiratory
      tract infections underwent microbiological investigations with fiber-optic
      bronchoscopy with bronchoalveolar lavage, blood and sputum culture and urine
      antigen test for type-specific polysaccharide capsular antigens of S. pneumoniae.
      RESULTS: When stratified for antibiotic treatment prior to microbiological
      sampling, three different groups of patients with documented or probable
      infection with S. pneumoniae could be identified. The first group comprised 14
      patients who were culture positive in one or more culture tests, where most
      (11/14) did not receive any antibiotic treatment within 24 hours of sampling. The
      second group consisted of nine patients with a positive urine antigen test where
      8/9 and 9/9 received antibiotic treatment 24 and 48 hours, respectively, prior to
      urine sampling. Only a single patient was positive in both systems, making a
      total of 22 patients with documented pneumococcal infection. As a positive
      culture test was dependent on the absence of antibiotic treatment, whereas a
      positive urine antigen test depended on antibiotic treatment within 48 hours, the
      two tests were complementary in the diagnosis of infection with S. pneumoniae.
      The third group of patients with probable pneumococcal infection were identified
      as 26% and 20% of the remaining 137 patients with unknown or known non
      pneumococcal etiology, respectively, who received recent antibiotic treatment
      within 2-4 weeks of diagnostic sampling. By comparison, 0% (p < 0.01) with
      documented pneumococcal infection received antibiotic treatment in weeks 2-4
      prior to microbiological sampling. As such a further eight patients should be
      expected to have infection with S. pneumoniae but would test negative in both
      culture tests and the urine antigen test because of antibiotic treatment within
      weeks 2-4 prior to sampling. CONCLUSION: The diagnosis of infection with S.
      pneumoniae is very dependent on whether or not recent (within 2-4 weeks) or
      immediate (within 48 hours) antibiotic treatment has been given prior to
      microbiological sampling of patients. The results suggest an optimized diagnostic
      strategy with, if possible, sampling for culture prior to antibiotic treatment,
      while sampling for pneumococcal antigens should wait 24-48 hours for antibiotic
      treatment.

PMID- 16095942
TI  - Effects of severe acute respiratory syndrome (SARS) coronavirus infection on
      peripheral blood lymphocytes and their subsets.
AB  - INTRODUCTION: Severe acute respiratory syndrome (SARS) caused large outbreaks of
      atypical pneumonia in 2003, with the largest localized outbreak occurring in
      Beijing, China. Lymphopenia was prominent amongst the laboratory abnormalities
      reported in acute SARS. METHODS: The effect of SARS on peripheral blood
      lymphocytes and their subsets was examined in 271 SARS coronavirus-infected
      individuals. RESULTS: There was a significant decrease in the CD45+, CD3+, CD4+,
      CD8+, CD19+ and CD16+/56+ cell counts over the five weeks of the SARS illness
      although CD4+/CD8+ ratios did not change significantly. The lymphopenia was
      prolonged, reaching a nadir during days 7-9 in the second week of illness before
      returning towards normal after five weeks, with the lowest mean CD4+ cell count
      of 317 cellsx10(6)/L at day 7, and CD8+ cell count of 239 cellsx10(6)/L at day 8.
      Patients with more severe clinical illness, or patients who died, had
      significantly more profound CD4+ and CD8+ lymphopenia. DISCUSSION: Lymphopenia is
      a prominent part of SARS-CoV infection and lymphocyte counts may be useful in
      predicting the severity and clinical outcomes. Possible reasons for the SARS
      associated lymphopenia may be direct infection of lymphocytes by SARS-CoV,
      lymphocyte sequestration in the lung or cytokine-mediated lymphocyte trafficking.
      There may also be immune-mediated lymphocyte destruction, bone marrow or thymus
      suppression, or apoptosis.

PMID- 16095943
TI  - [Radiotherapy for glioblastomas: from radiobiology to concomitant chemotherapy].
AB  - The prognosis of glioblastoma remains extremely poor. Clinical research has been
      very active for thirty years, and has explored all the concepts developed in the
      laboratories of radiobiology. Radiosensitisation of hypoxic tumours,
      hyperfractioned radiotherapy, external beam radiotherapy plus stereotactic
      radiosurgery or brachytherapy boost, and intensity modulated radiation therapy
      failed to improve the results of the treatment of these patients. Concomitant
      chemoradiotherapy has just obtained a new success in the treatment of
      glioblastoma. The addition of temozolomide to radiotherapy resulted in a
      statistically significant survival benefit with minimal acute additional
      toxicity. The challenge remains to improve clinical outcomes further, and some
      new research pathways are open.

PMID- 16095944
TI  - [Conformal radiation therapy with or without intensity modulation in the
      treatment of localized prostate cancer].
AB  - Conformal radiation therapy has now to be considered as a standard treatment of
      localized prostatic adenocarcinomas. Using conformational methods and intensity
      modulated radiation therapy requires a rigorous approach for their implementation
      in routine, focused on the reproducibility of the treatment, target volume
      definitions, dosimetry, quality control, setup positioning. In order to offer to
      the largest number of patients high-dose treatment, the clinicians must integrate
      as prognostic factors accurate definition of microscopic extension as well as the
      tolerance threshold of critical organs. High-dose delivery is expected to be most
      efficient in intermediary risks and locally advanced diseases. Intensity
      modulated radiation therapy is specifically dedicated to dose escalation. Perfect
      knowledge of classical constraints of conformal radiation therapy is required.
      Using such an approach in routine needs a learning curve including the physicists
      and a specific quality assurance program.

PMID- 16095945
TI  - Biomechanical impact of vertebroplasty. Postoperative biomechanics of
      vertebroplasty.
AB  - OBJECTIVES: To examine the biomechanisms underlying adjacent fractures following
      vertebroplasty, an emerging procedure to stabilize fractured vertebrae. In this
      procedure, bone cement is injected percutaneously into the vertebral cancellous
      bone. Once hardened, the cement offers mechanical reinforcement to the weakened
      vertebra. Recent clinical and biomechanical reports suggest that this procedure
      may cause new fractures adjacent to the one augmented. The cause and extend is
      unclear yet. The focus here is on the biomechanical hypothesis resulting from the
      rigid cement augmentation. METHODS: A combination of experimental and numerical
      studies, in additional to a review of recent clinical reports. RESULTS: The
      broader finding suggests that vertebroplasty changes the mechanical loading in
      adjacent vertebrae. Specifically, an increase in adjacent loading in the range of
      17% has been found. The mechanism underlying this increase seemed to stem from
      the excessive cement rigidity that reduced the endplate bulge of the augmented
      vertebra, thereby reducing the local spinal joint flexibility. The reduction in
      joint flexibility seeks to reverse itself by creating an increase in the inter
      vertebral disc pressure. The increased disc pressure seeks to relieve itself by
      increasing the load on the adjacent vertebra. The increased load on the adjacent
      vertebra relates directly to an increased risk of fracture. CONCLUSIONS: Although
      an increasing amount of evidence exists to support this theory of the origin of
      adjacent fractures, one must be cautious. Vertebroplasty is a relatively new
      procedure and further observations and, ultimately, prospective clinical studies
      are required to conclusively determine the cause and extend of adjacent
      fractures.

PMID- 16095946
TI  - Reliability and validity of shoulder tightness measurement in patients with stiff
      shoulders.
AB  - The purposes of this study were (1) to examine intratester and intertester
      reliability of measurement of anterior and posterior shoulder tightness in
      patients with stiff shoulders (SS), and (2) to assess construct validity by
      determining the relations between shoulder tightness, shoulder range of motion
      (ROM), and self-report measures of functional limitation. Anterior and posterior
      shoulder tightness were measured by two testers in below-chest abduction and
      cross-chest adduction tests with an inclinometer, respectively, in 16 patients
      with SS. Both the intratester and intertester reliability for shoulder tightness
      measurements were good (intratester ICC=0.84 and 0.91; intertester ICC=0.82 and
      0.89). The limit of intra-tester and inter-tester agreement (mean, -0.3+/-4.4
      degrees ) was acceptable as compared to the standard deviations of the
      measurements (range, 6.2-7.4 degrees ). Significant relationships between
      internal rotation and posterior shoulder tightness (R2=0.448, P=0.002), external
      rotation and anterior shoulder tightness (R2=0.499, P=0.003), and functional
      disabilities and posterior shoulder tightness (R2=0.432, P=0.006) were found.
      Significant correlations between shoulder internal rotation and cross-chest
      adduction, shoulder external rotation and below-chest abduction were observed,
      indicating that internal and external rotations might be related to posterior and
      anterior shoulder stiffness. The study also revealed significant relationship
      between functional disabilities and cross-chest adduction. Below-chest abduction
      and cross-chest adduction were found to provide reliable data. The construct
      validity of the abduction and adduction tests is supported by the relationship
      among these measurements, shoulder ROM, and functional disabilities in patients
      with SS.

PMID- 16095948
TI  - CSL: a notch above the rest.
AB  - CSL (CBF1, Suppressor of Hairless, Lag-1) is a transcription factor that is
      responsible for activating the genes downstream of the Notch signalling pathway,
      a pathway that is essential for the development of the nervous system and the
      differentiation of the haematopoietic system among others. In the absence of
      Notch signalling, CSL represses transcription of Notch target genes, and
      following activation by Notch, CSL is converted into a transcriptional activator
      and activates transcription of the same genes. These two opposing functions of
      CSL are mediated through interactions with distinct protein complexes. The Notch
      signalling pathway and its crucial cofactor CSL can maintain cells in an
      undifferentiated state, and have therefore been associated with a growing list of
      cancers. In addition, CSL has been co-opted by Epstein-Barr virus to mediate
      viral and host gene transcription following infection.

PMID- 16095949
TI  - GATA-1: one protein, many partners.
AB  - GATA-1, the founding member of the GATA transcription factor family, is essential
      for cell maturation and differentiation within the erythroid and megakaryocytic
      lineages. GATA-1 regulates the expression of many genes within these lineages and
      its functionality depends upon its ability to bind both DNA and protein partners.
      Disruption of either of these functions causes severe hematopoietic dysfunction
      and results in blood disorders, such as thrombocytopenia and anemia. Within this
      review, we will focus on the structural aspects of GATA-1 with regard to
      interactions with its many partners and the identification of several mutations
      that disrupt these interactions.

PMID- 16095950
TI  - Gene-environment processes in task persistence.
AB  - Task persistence is a construct that appears to have broad influence on child
      competence generally, from self regulation in carrying out tasks, to cognitive
      performance. In a recent developmental study of task persistence, Deater-Deckard
      and colleagues report that heritability of task persistence increased over time,
      whereas the contribution from the shared environment decreased during the
      transition from early to middle childhood. Two explanations for the developmental
      shift are discussed here: a choice hypothesis and a schooling hypothesis. An
      important next step lies in documenting gene-environment processes directly via
      hybrid research models, combining work in molecular biology with longitudinal
      observations of behavior.

PMID- 16095951
TI  - Metastases and their microenvironments: linking pathogenesis and therapy.
AB  - The pathogenesis of metastasis depends on multiple favorable interactions of
      tumor cells with host homeostatic mechanisms. Interruption of one or more of
      these interactions can lead to the inhibition or eradication of cancer
      metastases. For many years, all efforts to treat cancer concentrated on the
      inhibition of growth or the destruction of tumor cells. A strategy of both
      eradication of tumor cells (e.g. by chemotherapy and immunotherapy) and
      modulation of the host microenvironment (e.g. tumor vasculature and hypoxia) is
      an additional, relatively novel approach to cancer treatment. Recent advances in
      our understanding of the biological basis of cancer metastasis open up
      unprecedented opportunities for translating basic research to clinical treatment
      of cancer. This research includes the unraveling of the genetic make-up of tumors
      and genome-wide expression analyses, thereby identifying many potential targets
      for therapy. Drugs acting on tumor cells which have a metastasis-prone mutational
      or expression status (by classical or targeted chemotherapy) as well as drugs
      affecting host-mediated survival pathways must be combined in order to create
      therapeutic synergy. Therapeutic maneuvers may target receptor tyrosine kinases
      (EGFR, VEGFR, FGFR), chemokines or G-protein-coupled receptors (CXCR4, CXCR2,
      EphB2), hypoxia-inducible factor (HIF), and signaling pathways (c-Src, PI3K, Akt,
      chaperon complexes) in tumor cells. Moreover, stromal and immunological cells and
      their cytokines coordinate critical pathways that exert important roles in the
      ability of tumors to invade and metastasize, thus suppressive cytokines (IL-6 and
      IL-10) and neutralizing specific antibodies might subvert conditions for
      metastasis.

PMID- 16095952
TI  - Novel antimutagenic factors derived from the edible mushroom Agrocybe
      cylindracea.
AB  - Studies have shown that certain foods contain compounds with antigenotoxic
      activities. Here, we ask if dried powders and/or extracts from three edible
      mushrooms, Agrocybe cylindracea, Lentinula edodes and Pleurotus ostreatus, have a
      mitigating effect on genotoxicity. We used two in vivo assays: the Drosophila DNA
      repair test and the Drosophila wing spot test (also known as SMART) which
      measures somatic mutation and recombination. Eight carcinogens were tested with
      the mushroom powders: 2-AAF, aflatoxin B1, DMBA, IQ, MeIQx, MNU NDMA, and 4NQO.
      We found that A. cylindracea and P. ostreatus powders can suppress DNA damage
      induced by each of the mutagens we tested. In contrast, L. edodes has an
      inhibitory effect on DNA damage induced by only a sub-set of mutagens, namely
      aflatoxin B1, NDMA, MNU and 4NQO. In addition, A. cylindracea extracts were able
      to suppress somatic cell mutation induced by aflatoxin B1, MMC, MNU, NDMA, NMOR
      and 4NQO. These results suggest that Agrocybe genus mushrooms contain factors
      with antigenotoxic activity, including anti-recombinogenic activity. Furthermore,
      the antigenotoxic activity of A. cylindracea powder can be extracted in water but
      not in ethyl acetate or methanol, and is sensitive to heat treatment. The data
      suggest that there is a novel antigenotoxic factor(s) in A. cylindracea, possibly
      in the form of a peptide or protein.

PMID- 16095953
TI  - Optical properties of Ag/CdTe nanocomposite self-organized by electrostatic
      interaction.
AB  - Ag/CdTe nanocomposite was prepared via self-organization process by electrostatic
      interaction between positively charged CdTe quantum dots and negatively charged
      Ag nanoparticles and examined with respect to their optical properties. The
      positively charged CdTe quantum dots and negatively charged Ag nanoparticles were
      synthesized separately by modifying nanoparticles surface with cationic and
      anionic thiol compounds, respectively. The result showed that the mixing ratio of
      Ag nanoparticles to CdTe quantum dots is an important parameter for controlling
      resulting composites. The resulting solution is optically transparent if one
      component is in excess. Photoluminescence of CdTe quantum dots undergoes
      considerably quenching if CdTe nanocrystals are in excess and SERS spectra of
      BVPP absorbed on Ag colloid became stronger if Ag nanoparticles are in excess.
      Nevertheless, while the ratio is approximately 1, micrometer-sized solid
      composite is obtained with the elapse of 1h after mixing. SERS spectra for solid
      composite only exhibit the signals of the CdS nanocrystal which reflected that
      prolonged refluxing during the synthesis leads to a partial hydrolysis of the
      thiols and to the incorporation of the sulfur from the thiol molecules into the
      the growing nanoparticles to form mixed CdTe(S) nanocrystal, similar to CdTe/CdS
      core/shell structure. From the results, we conclude that optical properties of
      Ag/CdTe are dependent on the mixing ratio of both nanoparticles.

PMID- 16095954
TI  - Stability and conformation of the complexes of riboflavin with aromatic hydroxy
      compounds in an aqueous medium.
AB  - Overall equilibrium constants K' for the formation of molecular complexes of
      riboflavin with the conjugate forms of different aromatic hydroxy compounds are
      greater in magnitude than those involving the protonated forms of the hydroxy
      compounds. There is good agreement between the K(B) values determined by using
      absorption and emission methods. Based on the magnitude of K(B), it is possible
      to differentiate between the donor capacities of the hydroxy compounds in the
      charge transfer complexes with riboflavin. Molecular modeling studies indicate
      stacking interactions for all the systems in an aqueous medium.

PMID- 16095955
TI  - Spectral studies of SnO2 nanofibres prepared by electrospinning method.
AB  - Tin oxide nanofibres with 100-150 nm diameter has been prepared, for the first
      time by calcination of poly(vinyl acetate) (PVAc)/SnO2 composite fibres prepared
      by electrospinning method as precursor. Scanning electron microscopic images
      revealed cylindrical morphology of the fibres after calcination at 600 degrees C.
      Both, X-ray diffraction (XRD) and Raman spectral data confirmed the presence of
      phase pure tetragonal rutile tin oxide after calcination process. Room
      temperature photoluminescence (PL) spectra of tin oxide nanofibres under
      excitation at 325 nm wavelength show a strong green emission at 525 nm with a
      band gap of 2.41 eV. FT-IR spectra confirmed the formation of pure tin oxide
      after calcination at 600 degrees C and complete removal of PVAc during
      calcination. UV-vis spectrum of the fibres showed absorption at 315 nm due to the
      direct electron transfer in tin oxide.

PMID- 16095956
TI  - Background defining during the imine formation reaction in FT-IR liquid cell.
AB  - Imine formation is a very important chemical reaction because of its relevance to
      biological process. Therefore, it is crucial to follow whole reaction process in
      detail. The current work performed to monitor the whole imination reaction in
      real time in liquid cell by FT-IR spectroscopy. The complex spectral futures due
      to solvent, unreacted reagents, acid catalysis and other additives are eliminated
      by defining a background at the beginning or at any time during the reaction.
      This procedure also makes it possible to monitor the changes in the concentration
      of each component in the liquid cell. The consumption of the functional groups of
      the reagents results in absorbance due to the direct difference spectra while the
      appearance of functional groups is monitored as percentage transmittance. The
      concentration changes in the cell arising from the reaction gives the product
      spectra without having to isolate it from the mixture. It is also possible to see
      the intermediates appearing and disappearing during the reaction. This report
      also illustrates a brief application of the technique by time dependence of the
      peak highs in absorption (ABS) mode.

PMID- 16095957
TI  - The electro-oxidative activity of cysteine on the Au electrode as evidenced by
      surface enhanced Raman scattering.
AB  - It is demonstrated from the surface-enhanced Raman scattering that cysteine is
      adsorbed on the Au electrode via its carboxylate moiety. The mechanism is mainly
      via the charge transfer involving the pi electron-rich carboxylate moiety. The
      adsorption of cysteine is weak that its diffusion on the Au surface is possible.
      The collision of two cysteine molecules may lead to the electro-oxidative
      formation of cystine in an irreversible way due to that the disulfide bond is not
      in the close vicinity of the electrode and its rupture is hampered. The physical
      difference as compared to its adsorption on the Ag electrode is stressed.

PMID- 16095958
TI  - Intense blue up-conversion luminescence in Tm3+/Yb3+ codoped oxyfluoride glass
      ceramics containing beta-PbF2 nanocrystals.
AB  - Up-conversion luminescence properties of a Tm3+/Yb3+ codoped oxyfluoride glass
      ceramics under 980 nm excitation are investigated. Intense blue emission centered
      at 476 nm, corresponding to 1G4-->3H6 transitions of Tm3+ was simultaneously
      observed in the transparent oxyfluoride glass ceramics at room temperature. The
      intensity of the blue up-conversion luminescence in a 1 mol% YbF3-containing
      glass-ceramic was found to be about 40 times stronger than that in the precursor
      oxyfluoride glass. The reason for the intense Tm3+ up-conversion luminescence in
      the oxyfluoride glass-ceramics is discussed. The dependence of up-conversion
      intensities on excitation power and possible up-conversion mechanism are also
      evaluated.

PMID- 16095959
TI  - Theoretical studies of molecular structure and vibrational spectra of 2-amino-5
      phenyl-1,3,4-thiadiazole.
AB  - The molecular geometry and vibrational frequencies of 2-amino-5-phenyl-1,3,4
      thiadiazole (C8H7N3S) in the ground state has been calculated using the Hartree
      Fock and density functional method (B3LYP) with 6-31G(d) basis set. The optimized
      geometric bond lengths and bond angles obtained by using HF and DFT (B3LYP) show
      the best agreement with the experimental data. Comparison of the observed
      fundamental vibrational frequencies of 2-amino-5-phenyl-1,3,4-thiadiazole
      (C8H7N3S) and calculated results by density functional B3LYP and Hartree-Fock
      methods indicate that B3LYP is superior to the scaled Hartree-Fock approach for
      molecular vibrational problems.

PMID- 16095960
TI  - Commitment of project participants to developing health care services based on
      the internet technology.
AB  - BACKGROUND: When developing Information and Communication Technology (ICT), such
      as services for the decision-making process, skilled health care professionals
      with their comprehensive knowledge of patients/clients are essential contributors
      to the project. Careful evaluation is needed to assess the effectiveness of
      project management as well as to analyze the commitment of the personnel to goal
      attainment. OBJECTIVE: In the course of the development of integrated maternity
      care services, the commitment of project participants (n=48) was evaluated. What
      factors enhanced or impaired their commitment to the project work? METHODS:
      Questionnaire (n=80, response rate 60%) with quantitative analysis as well as
      open-ended questions with qualitative content analysis. RESULTS: Positive
      commitment was related to a confidential and open atmosphere during the project.
      The utilization of personal skills and experience was appreciated. Differences in
      the working principles and cultures between the participating organizations
      complicated fluent collaboration. To encourage commitment, a lot of attention
      should be paid to internal communication as well as the effective realization of
      project tasks. CONCLUSION: The strength of the project was the highly innovative
      and confidential atmosphere. The well-established project goals, the highly
      inspired project team, and the effective co-operation between the project manager
      and the core group helped to deepen overall commitment in the project.

PMID- 16095961
TI  - Electronic patient-provider communication: will it offset office visits and
      telephone consultations in primary care?
AB  - BACKGROUND AND AIM: Electronic patient-provider communication promises to improve
      efficiency and effectiveness of clinical care. This study aims to explore whether
      a secure web-based messaging system is an effective way of providing patient care
      in general practices. METHOD: We conducted a randomised controlled trail and
      recruited 200 patients from the waiting area in one primary clinic in Norway.
      Participants were randomised to either the intervention group, which received
      access to a secure messaging system, or the control group receiving standard care
      without such access. Primary outcome measures were number of online
      consultations, telephone consultations and office visits in the two groups. Data
      were derived from patient records and collected 1 year prior to (baseline), and 1
      year after the intervention. RESULTS: Forty-six percent of the patients who were
      given access to the messaging system (n=99) used the online communication system
      on at least one occasion (ranging from 1 to 17 messages per patient per year). A
      total of 147 electronic messages were sent to six general practitioners during a
      1-year trial period. Eleven percent of the messages were to schedule an
      appointment. In 10% of the messages, the GP was unable to respond adequately and
      recommended an office visit. The reduction in office visits over time was greater
      for the intervention group than for the control group (P=0.034). There was
      however no significant difference in the number of telephone consultations
      between the groups during the study (P=0.258). CONCLUSION: The use of a secure
      electronic messaging system reduced the number of office visits at the general
      practice, but not phone consultations.

PMID- 16095962
TI  - A hybrid method for relation extraction from biomedical literature.
AB  - PURPOSE: Over recent years, there has been a growing interest in extracting
      entities and relations from biomedical literature. There are a vast number of
      systems and approaches being proposed to extract biological relations, but none
      of them achieves satisfactory results. These methodologies are either parsing
      based or pattern-based, which are not competent to handle the grammatical
      complexities of biomedical texts, or too complicated to be adapted. It is well
      known that appositive, coordinative propositions and such grammatical structures
      are extremely common in biomedical texts, particularly in full texts. However,
      these problems are still untouched for most of researchers. METHODS: In this
      paper, we have proposed a new approach, which is hybrid with both shallow parsing
      and pattern matching, to extract relations between proteins from scientific
      papers of biomedical themes. In the method, appositive and coordinative
      structures are interpreted based on the shallow parsing analysis, with both
      syntactic and semantic constraints. Then long sentences are splitted into sub
      ones, from which relations are extracted by a greedy pattern matching algorithm,
      along with automatically generated patterns. RESULTS: Our approach is
      experimented to extract protein-protein interactions from full biomedical texts,
      and has achieved an average F-score of 80% on individual verbs, and 66% on all
      verbs. With the help of shallow parsing analysis, pattern matching is improved
      remarkably. Compared with the traditional pattern matching algorithm, our
      approach achieves about 7% improvement of both precision and F-score. In contrast
      to other systems, our approach achieves performance comparable to the best. A
      demo system has been available at http://spies.cs.tsinghua.edu.cn.

PMID- 16095963
TI  - Results of a survey on medical error reporting systems in Korean hospitals.
AB  - BACKGROUND: Recent data suggest that medical injuries, or adverse events,
      represent an important international problem, and that many are caused by errors.
      Spontaneous reporting is the main tool used to detect errors and adverse events
      in most countries, and reporting systems are believed to be important for
      improving patient safety. Increasingly, such reporting can be done using
      information systems, and information systems are widely used in Korea. However,
      few data are available regarding the use of electronic medical error reporting
      systems in Korea. OBJECTIVES: The objectives of this study were to investigate
      the present status of reporting system of Korean hospitals, and to compare the
      current status of medical error reporting systems with that of other health
      information sub systems. METHODS: The chairs of nursing departments of all 283
      hospitals nationwide with more than 100 beds were surveyed using a structured
      questionnaire. The response rate was 35%. In addition, two reports on the
      national use of health information systems in Korea from 1999 and 2003 were
      analyzed. RESULTS: Among reporting hospitals (n=99), medical errors were reported
      on paper in 75 hospitals (77%), verbally in 30 hospitals (30%), using word
      processing in 13 hospitals (13%), and using the hospital information system in
      only three hospitals (3%). In contrast, there was widespread and increasing use
      of health information technology (HIT) in areas such as medication
      administration, inpatient and outpatient order entry, and radiology. CONCLUSIONS:
      While HIT is increasingly widely used in Korea in many areas, it is not being
      used for error reporting. Increasing the use of electronic reporting systems, and
      systemically evaluating the medical errors and adverse events reported, represent
      essential steps for reducing systemic errors and improving patient safety.

PMID- 16095964
TI  - Identification of hepatitis C virus 1b-derived peptides recognized by both
      cellular and humoral immune systems in HCV1b(+) HLA-A24(+) patients.
AB  - Despite scientific advances, the therapeutic options for hepatitis C virus (HCV)
      are limited by poor response rates. HCV1b is particularly resistant to standard
      interferon therapy. The inhibition of the progression of chronic hepatitis and
      liver cirrhosis and the prevention of the occurrence and recurrence of
      hepatocellular carcinoma (HCC) are important and thus, there is a need for new
      therapeutic modalities for HCV1b infection. We, therefore, investigated highly
      immunogenic peptides and report in this study three novel candidate peptides (at
      positions 711-720 in envelope 2 protein, 885-893 in non-structural protein 2 and
      1716-1724 in non-structural protein 4B) among 35 peptides of conserved regions of
      HCV1b proteins containing HLA-A24 binding motifs tested. Namely, HCV(711-720),
      HCV(885-893) and HCV(1716-1724) induced HLA-A24-restricted and peptide-specific
      cytotoxic T lymphocytes (CTLs) activity in peripheral blood mononuclear cells
      (PBMCs) from 7, 6 and 5 of 12 patients and also were recognized by plasma of 8, 5
      and 7 of 12 HCV1b(+) patients, respectively. These results may provide new
      insight into the development of a peptide-based specific immunotherapy for
      HCV1b(+) HLA-A24(+) patients.

PMID- 16095965
TI  - Current management of the hepatorenal syndrome.
AB  - Hepatorenal syndrome (HRS) is a serious complication of advanced liver disease.
      Historically, the development of HRS was considered a pre-terminal event due to a
      lack of efficacious therapy. Although liver transplantation remains the optimum
      therapy for HRS, many patients may be unsuitable for liver grafting. In addition,
      organ shortage may necessitate the institution of alternative pharmacological
      therapies to bridge patients to transplantation or to maintain renal function.
      This article reviews the definitions of Types-1 and -2 HRS, and addresses
      strategies for the prevention of the syndrome. It will also discuss management
      approaches to the cirrhotic patient with renal failure, specifically, assessment
      of novel vasoconstrictor therapies, such as vasopressin analogues, alpha
      adrenoreceptor agonists, and the use of transjugular intra-hepatic shunts either
      alone or in combination with other therapeutic agents.

PMID- 16095966
TI  - Strategies and computational tools for improving randomized protein libraries.
AB  - In the last decade, directed evolution has become a routine approach for
      engineering proteins with novel or altered properties. Concurrently, a trend away
      from purely 'blind' randomization strategies and towards more 'semi-rational'
      approaches has also become apparent. In this review, we discuss ways in which
      structural information and predictive computational tools are playing an
      increasingly important role in guiding the design of randomized libraries: web
      servers such as ConSurf-HSSP and SCHEMA allow the prediction of sites to target
      for producing functional variants, while algorithms such as GLUE, PEDEL and
      DRIVeR are useful for estimating library completeness and diversity. In addition,
      we review recent methodological developments that facilitate the construction of
      unbiased libraries, which are inherently more diverse than biased libraries and
      therefore more likely to yield improved variants.

PMID- 16095967
TI  - Life, illness and death--existential reflections of a Swedish sample of patients
      who have undergone curative treatment for breast or prostatic cancer.
AB  - The aim of this study is to describe cancer patients' existential reflections and
      how these reflections were met by the nursing staff. A qualitative method of data
      collection was used. Ten patients with breast- or prostate cancer who had
      completed curative treatment were interviewed. The results showed that the cancer
      diagnosis resulted in existential reflections in some of the patients. These
      reflections concerned the meaning of life, God/a higher power, health, work,
      relations and sexuality. Reflections on the cancer consisted in beliefs about the
      causes of cancer, treatment and cancer and sexuality. It could also be seen that
      loss of important life values, such as health and sexuality could lead to loss of
      meaning of life. Explicit reflections on sexuality were only made by two of the
      men in the study. The patients reported a need of existential support as well as
      obstacles for giving such support. Obstacles could be lack of time and lack of
      continuity, as well as lack of knowledge resulting in an inability to identify
      existential issues. Some of the patients had wanted existential support from
      nurses, while others received the support they needed from family and friends.

PMID- 16095968
TI  - Caring for carers: a prospective audit of nurse specialist contact with families
      and carers of patients with lung cancer.

PMID- 16095969
TI  - Beta-lactams against methicillin-resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) have developed resistance to
      virtually all non-experimental antibiotics. They are intrinsically resistant to
      beta-lactams by virtue of newly acquired low-affinity penicillin-binding protein
      2A (PBP2A). Because PBP2A can build the wall when other PBPs are blocked by beta
      lactams, designing beta-lactams capable of blocking this additional target should
      help solve the issue. Older molecules including penicillin G, amoxicillin and
      ampicillin had relatively good PBP2A affinities, and successfully treated
      experimental endocarditis caused by MRSA, provided that the bacterial
      penicillinase could be inhibited. Newer anti-PBP2A beta-lactams with over 10-fold
      greater PBP2A affinities and low minimal inhibitory concentrations were
      developed, primarily in the cephem and carbapenem classes. They are also very
      resistant to penicillinase. Most have demonstrated anti-MRSA activity in animal
      models of infection, and two--the carbapenem CS-023 and the cephalosporin
      ceftopibrole medocaril--have proceeded to Phase II and Phase III clinical
      evaluation. Thus, clinically useful anti-MRSA beta-lactams are imminent.

PMID- 16095970
TI  - Interferon gene regulation: not all roads lead to Tolls.
AB  - Many infectious agents elicit a type I interferon response but, until recently,
      the molecular details that coordinate interferon (IFN)-alpha and -beta expression
      during infection were unknown. Innate immune pattern recognition receptors,
      including Toll-like receptors and cytoplasmic RNA helicases such as retinoic acid
      inducible gene, that sense viral nucleic acids have been discovered. Using
      distinct mechanisms, these receptors trigger cellular signaling pathways,
      culminating in the activation of interferon regulatory factors that
      transcriptionally induce IFN-alpha and IFN-beta genes.

PMID- 16095971
TI  - Epitope spreading within lupus-associated ribonucleoprotein antigens.
AB  - Autoantibodies reactive with several cellular antigens are present in the sera of
      patients with systemic lupus erythematosus. Polypeptides within the Ro-RNP
      complex and the snRNP complex are often targeted by these autoantibodies. One of
      the mechanisms responsible for their evolution is that of epitope spreading.
      Experimental animal model systems provide evidence for this. This review
      discusses the animal model systems of epitope spreading within these
      ribonucleoprotein antigens, the mechanisms of epitope spreading, and its
      relevance for disease pathogenesis.

PMID- 16095972
TI  - Gene therapy for malignant glioma: current clinical status.
AB  - Glioblastoma is an aggressive brain tumor with a dismal prognosis. Gene therapy
      may offer a new option for the treatment of these patients. Several gene therapy
      approaches have shown anti-tumor efficiency in experimental studies, and the
      first clinical trials for the treatment of malignant glioma were conducted in the
      1990s. HSV-tk gene therapy has been the pioneering and most commonly used
      approach, but oncolytic conditionally replicating adenoviruses and herpes simplex
      virus mutant vectors, p53, interleukins, interferons, and antisense
      oligonucleotides have also been used. During the past few years, adenoviruses
      have become the most popular gene transfer vectors, and some recent randomized,
      controlled trials have shown significant anti-tumor efficacy in clinical use.
      However, efficient gene delivery into the brain still presents a major problem,
      and there is a lack of definitive phase III trials, which would avoid potential
      problems associated with a small number of patients, inadvertent patient
      selection, and overinterpretation of results based on a few long-time survivors.
      For clinical efficacy, median survival is one of the most rigorous endpoints. It
      is used here to evaluate the usefulness of various treatment approaches and
      current clinical status of gene therapy for malignant glioma.

PMID- 16095973
TI  - Cell death induced by the herpes simplex virus-1 thymidine kinase delivered by
      human immunodeficiency virus-1-based virus-like particles.
AB  - HIV-1 Nef incorporates into virions at low levels, likely about 10 molecules per
      viral particle. Here, we describe a Nef mutant (Nef7) apparently showing more
      than 100-fold higher efficiency of virion incorporation. Interestingly, Nef7 can
      act as a cargo molecule for protein delivery into the cells, as its virion
      incorporation appeared conserved even upon C-terminal fusion with proteins of up
      to 30 kDa. This was demonstrated first by assessing the intracellular
      fluorescence of cells challenged with lentivirus-based virus-like particles
      (VLPs) pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV
      G) and incorporating Nef7 fused with the green fluorescent protein. Furthermore,
      the biologic activity of products delivered by Nef7-based VLPs was demonstrated
      by tagging Nef7 with the herpes simplex virus-1 thymidine kinase (HSV-1 TK). In
      fact, we observed that both cell lines and primary human macrophages challenged
      with (VSV-G) Nef7/TK VLPs died after 5 to 7 days of treatment with ganciclovir
      (GCV). In sum, our findings support the notion that Nef7-based VLPs can be
      considered platforms for original systems of protein delivery. In particular, the
      here- described Nef7/TK VLPs represent a first applicative example opening the
      way toward new HSV-1 TK/GCV-based cell suicide therapies circumventing cell gene
      engineering procedures.

PMID- 16095974
TI  - The Eustachian valve in pulmonary embolism: rescue or perilous?
AB  - This case illustrates the Eustachian valve as an ambiguous entity. By tethering a
      thrombus the valve prevented a major pulmonary embolism. However, in combination
      with a patent foramen ovale, it directs the thrombus into the left atrium,
      creating a threat for systemic embolisms.

PMID- 16095975
TI  - Echocardiographically detected mass "in transit" in early amniotic fluid
      embolism.
AB  - BACKGROUND: Amniotic fluid embolism is a catastrophic illness related to the
      passage of fetal material into the pulmonary circulation causing cardiovascular
      collapse. CASE: A 29-year-old female sustained cardiopulmonary arrest during
      delivery presumably due to amniotic fluid embolism. A right atrial mass "in
      transit" was detected by echocardiography. It had an appearance and pattern of
      motion that was suggestive of a gelatinous consistency and is likely to have been
      an amniotic fluid embolus. There was also evidence of acute right ventricular
      overload. CONCLUSION: We recommend that echocardiography be considered early on
      such conditions to gain more insight into the pathogenesis of this complication.

PMID- 16095976
TI  - Does alexithymia differentiate between patients with nonepileptic seizures,
      patients with epilepsy, and nonpatient controls?
AB  - Considering the evidence of an association between alexithymia and somatization,
      this study aimed to discover whether alexithymia could distinguish patients with
      psychogenic nonepileptic seizures (NES) from those with epilepsy (ES) and
      nonpatient controls (C). Toronto Alexithymia Scale (TAS-20) scores were obtained
      from 21 matched participants from each of these groups, together with measures of
      anxiety and depression. Overall TAS-20 scores did not differentiate the three
      groups after controlling for anxiety and depression, but scores on certain
      subscales of the TAS-20 differed significantly between the patient groups and the
      controls. Although alexithymia could not discriminate individuals with NES from
      those with organic manifestations, whether the etiology of alexithymia may differ
      according to patient group was discussed. Given that 90.5% of NES patients were
      identified as alexithymic, treatment approaches used for individuals with
      alexithymia may be usefully applied to those with NES.

PMID- 16095977
TI  - Effects of benzo(k)fluoranthene exposure on the biomarkers of scallop Chlamys
      farreri.
AB  - Scallops (Chlamys ferrari) were cultured for 30 days in seawater containing
      benzo(k)fluoranthene (BkF) at 0.5, 1.0 and 10.0 microg/L. No effects were noted
      on 7-ethoxyresorufin O-deethylase (EROD) activity in digestive gland at low
      concentrations (0.5 and 1 microg/L) of BkF, but BkF increased the glutathione-S
      transferase (GST) activity. At 10 microg/L BkF increased EROD activity
      significantly, and depressed GST activity. Superoxide dismutase (SOD), catalase
      (CAT) and glutathione peroxidase (GPx) in digestive gland increased significantly
      in 0.5 and 1 microg/L BkF. In 10 microg/L concentrations of BkF, the activity of
      three antioxidant enzymes increased first and reached a peak after a few days,
      before tapering off towards the end of the 30 day exposure. In high
      concentrations of BkF, activity of three antioxidant enzymes in gill showed an
      early peak (12 h), before dropping off. Lipid peroxidation (LPO) levels increased
      along with sampling times, and there were time- and concentration-effects between
      LPO levels and BkF. The responses of the gills and the digestive gland were not
      always parallel which can be explained by differences in the bioavailability of
      the toxicant. The performance of each biomarker is assessed in the context of the
      role and advantages of selecting a battery of biomarkers for detecting
      contamination problems. The use of C. ferrari as a sentinel species for
      biomonitoring potential toxic effects in situ is discussed as well as mechanisms
      of BKF toxicity and alexipharmic strategies of C. ferrari.

PMID- 16095978
TI  - Serum fibrillin-antifibrillin immune complexes among diabetic children.
AB  - The fibrillins are large glycoproteins components of 10-nm microfibrils found in
      the extracellular matrix of most tissues. Microfibrils play a role in elastic
      fiber assembly and serve to link cells to elastic fibers in the extracellular
      matrix. Fibrillin-1 (FBN-1) and -2 (FBN-2) are large, secreted glycoproteins
      known to be components of extracellular matrix microfibrils located in the
      vasculature, basement membrane, and various connective tissues and are often
      associated with a superstructure known as the elastic fiber. Anti-fibrillin
      antibodies found in some autoimmune diseases could form circulating immune
      complexes (CIC) with corresponding antigens. Type 1 (insulin-dependent) diabetes
      mellitus is an autoimmune disease leading to formation of different types of
      autoantibodies. To determine the possible presence of FBN-anti-FBN CIC (IgG and
      IgM) were studied by modified version of ELISA 35 children with Type 1 diabetes
      mellitus (mean age--12.37+/-3.77 years, diabetes duration 4+/-3.5 years). Eight
      of the diabetics had vascular complications. Twenty healthy children (mean age-
      11.58+/-2.89 years) were used as controls. Diabetics showed statistically
      significant higher levels of FBN-anti-FBN-2 CIC - IgG (0.303+/-0.076 vs. 0.252+/
      0.029; p=0.029) and IgM (0.415+/-0.085 vs. 0.348+/-0.069; p=0.018) compared to
      the control group. FBN-anti-FBN-1 CIC IgM correlate with diabetes duration
      (r=0.52; p=0.0015) and BMI (r=0.33, p=0.053) while FBN-anti-FBN-1 CIC IgG
      correlate with serum Zinc (r=0.49, p=0.006). FBN-anti-FBN-2 CIC IgG correlate
      with microalbuminuria (r=0.65, p=0.0046) and retinopathy (r=0.61, p=0.0001). This
      study suggests that there may be a relationship of levels of FBN-anti-FBN-2 CIC
      IgG with the development of diabetic microangiopathy. Of course the number of the
      tested patients is limited for definitive conclusions. Although the meaning of
      these results is still being determined, the measurement of FBN-anti-FBN CIC may
      represent immunologic markers of FBN metabolism.

PMID- 16095979
TI  - Alpha-1B adrenoceptors mediate neurogenic constriction in mesenteric arteries of
      normotensive and DOCA-salt hypertensive mice.
AB  - The contribution of alpha-1 adrenergic receptor (alpha1-AR) subtypes to
      neurogenic constrictions of mesenteric resistance arteries from SHAM and
      deoxycorticosterone acetate-salt (DOCA-salt) hypertensive mice was assessed.
      Frequency-response curves (0.5-30 Hz) for transmural stimulation-evoked
      contractions were examined in SHAM and DOCA-salt arteries in vitro in the absence
      (control) and presence of prazosin (0.1 microM), PPADS (10 microM), yohimbine (1
      microM), 5-methylurapidil (5-MU; 0.1 microM), L-765,314 (1 microM) and BMY-7378
      (0.3 microM); selective antagonists at alpha1-, P2X, alpha2-, alpha1A-, alpha1B-,
      and alpha1D-AR, respectively. In SHAM arteries, prazosin but not PPADS inhibited
      neurogenic responses. L-765,314 substantially inhibited neurogenic responses
      while 5-MU had a small inhibitory effect. BMY-7378 did not alter contractile
      responses at all. In DOCA-salt arteries, prazosin reduced neurogenic responses
      with no further significant inhibition seen with PPADS. L-765,314 antagonized
      neurogenic constrictions to a level similar to that seen in SHAM arteries.
      Furthermore, 5-MU and BMY-7378 did not affect these responses. The density of
      noradrenergic nerves (assessed using glyoxylic acid-induced fluorescence) or
      norepinephrine (NE) content was not altered by DOCA-salt hypertension. These
      results indicate that NE is the primary mediator of neurogenic constriction of
      murine mesenteric arteries. Nerve-released NE acts primarily at alpha1B-and to a
      lesser extent at alpha1A-ARs in SHAM arteries whereas NE mediates neurogenic
      constrictions in DOCA-salt arteries by acting at alpha1B-ARs.

PMID- 16095980
TI  - The irresistible resistance of nonsense: Evolutionary adaptation of termination
      codons to minimize the effects of common DNA damage.

PMID- 16095981
TI  - Absence of an hypoxic depression of metabolism in preproenkephalin knockout mice.
AB  - Opioids inhibit breathing in mammals, especially in newborns, and are also
      implicated in the control of hypoxic anapyrexia. We measured breathing patterns
      and metabolic responses to 12% oxygen in six adult male wildtype C57B/6J mice and
      six preproenkephalin knockout (PPNK-/-) mice in a flow-through respirometer and
      barometric plethysmograph with ambient temperature maintained in the
      thermoneutral zone. Breathing air, there was no significant difference between
      the two groups of mice in ventilation ((.)V), oxygen consumption ((.)V(O(2)),
      convection requirement ((.)V/(.)V(O(2)), tidal volume (V(t)), frequency (f), or
      inspiratory time (T(i)); however, PPNK-/- mice had a significantly shorter
      expiratory time (T(e)). The breathing pattern response to 5% CO(2) was the same
      between wildtype and PPNK-/- in terms of absolute values, but the % change in
      V(t) was greater in the wildtype. Breathing 12% O(2), there was no significant
      difference in V , V(t), f, T(i), T(e) or body temperature between groups, but
      there was a significant difference in (.)V(O(2) (PPNK-/- 1.24+/-0.05 ml O(2)min(
      1) versus 0.91+/-0.05 for wildtype, P<0.001) and % change in (.)V(O(2), (2.3+/
      6.6% for PPNK-/- versus -28+/-3.8% for wildtype); in ((.)V/(.)V(O(2)), (54+/-4
      versus 78+/-10, P<0.05) and the % change in (.)V/(.)V(O(2), (37+/-9 versus 131+/
      28, P<0.01). These data implicate enkephalin as a signaling molecule in the
      control of hypoxic depression of metabolism in mice.

PMID- 16095982
TI  - Determination of testosterone concentrations in rat plasma using liquid
      chromatography-atmospheric pressure chemical ionization mass spectrometry
      combined with ethyl oxime and acetyl ester derivatization.
AB  - A quantitative method for measuring testosterone (T) concentrations in rat plasma
      was developed using ethyl oxime and acetyl ester derivatization and liquid
      chromatography-atmosphere pressure chemical ionization tandem mass spectrometry
      (LC-APCI-MS/MS). The method utilizes a solid phase extraction with Varian Bond
      Elut C18, a derivatization process to form testosterone ethoxime acetate and LC
      APCI-MS/MS with a reversed phase LC and a C8 column. This method is capable of
      detecting testosterone concentrations as low as 0.2 ng/ml in a 0.05 ml sample of
      rat plasma. This method can be used as a sensitive chromatography-based assay for
      small sample volumes of rat blood.

PMID- 16095983
TI  - Liquid chromatography-tandem mass spectrometry analysis of anisodamine and its
      phase I and II metabolites in rat urine.
AB  - A sensitive and specific method for the analysis of anisodamine and its
      metabolites in rat urine by liquid chromatography-electrospray ionization tandem
      mass spectrometry (LC-MS/MS) was developed. Various extraction techniques (free
      fraction, acid hydrolyses and enzyme hydrolyses) and their comparison were
      carried out for investigation of the metabolism of anisodamine. After extraction
      procedure the pretreated samples were injected on a reversed-phase C18 column
      with mobile phase (0.2 ml/min) of methanol/0.01% triethylamine solution (adjusted
      to pH 3.5 with formic acid) (60:40, v/v) and detected by MS/MS. Identification
      and structural elucidation of the metabolites were performed by comparing their
      changes in molecular masses (DeltaM), retention-times and full scan MS(n) spectra
      with those of the parent drug. At least 11 metabolites (N-demethyl-6beta
      hydroxytropine, 6beta-hydroxytropine, tropic acid, N-demethylanisodamine,
      hydroxyanisodamine, anisodamine N-oxide, hydroxyanisodamine N-oxide, glucuronide
      conjugated N-demethylanisodamine, sulfate conjugated and glucuronide conjugated
      anisodamine, sulfate conjugated hydroxyanisodamine) and the parent drug were
      found in rat urine after the administration of a single oral dose 25mg/kg of
      anisodamine. Hydroxyanisodamine, anisodamine N-oxide and the parent drug were
      detected in rat urine for up 95 h after ingestion of anisodamine.

PMID- 16095984
TI  - Recent studies on the electrospray ionisation mass spectrometric behaviour of
      selected nitrogen-containing drug molecules and its application to drug analysis
      using liquid chromatography-electrospray ionisation mass spectrometry.
AB  - This review presents recent studies on the electrospray ionisation mass
      spectrometry (ESI-MS) of selected N-containing drug molecules, their metabolites,
      formulation degradation products and process impurities taken from both studies
      in the author's laboratory and the recent literature using the Web of Knowledge
      database. Molecules of mass less than 500 Da are chosen according to selected
      structural classes in which they give ESI signals primarily in the positive ion
      mode as [M+H]+ ions. The structural classes are drugs with amine-containing side
      chains, drugs with N-containing saturated ring structures, drugs with N
      containing unsaturated ring structures and quaternary ammonium drugs. Details are
      given on the fragmentations, where available, that these ionic species exhibit in
      source and in ion-trap, triple quadrupole and time-of flight mass spectrometers.
      Fragmentation data, again where available, using electron impact mass
      spectrometry (EI-MS) is included for comparison. A review of applications for the
      period 2004-2005, again taken from the Web of Knowledge database, of the
      technique liquid chromatography-electrospray ionisation mass spectrometry (LC-ESI
      MS) to the detection and determination of these N-containing drug molecules in
      biomatrices, pharmaceutical formulations, etc., is then made. Analytical
      information on, for example, sample concentration techniques, LC separation
      conditions, recoveries from biological media, degradation products and limits of
      detection (LODs) are provided. Comparisons, where available, are also made with
      rival analytical techniques such as gas liquid chromatography-mass spectrometry
      (GLC-MS), capillary electrophoresis-electrospray ionisation mass spectrometry (CE
      ESI-MS) and stripping voltammetry (SV).

PMID- 16095985
TI  - Quantification of rotavirus-like particles by gel permeation chromatography.
AB  - There is a lack of accurate and practical methods that require only small amounts
      of sample for quantifying virus-like particles (VLP). In this work, gel
      permeation (GP) HPLC was used to quantify double-layered rotavirus-like particles
      (dlRLP) produced in insect cells. The proposed methodology utilized two columns
      in series (pore sizes of 200 and 50 nm) and had a high precision (relative
      standard deviation below 5%). GP-HPLC not only allowed the routine quantification
      of dlRLP, but also of assembly intermediaries and other viral structures present
      in the samples. For the first time, kinetics of dlRLP accumulation could be
      followed. This methodology is valuable for designing new production processes and
      for optimizing dlRLP monitoring.

PMID- 16095986
TI  - Quantitative analysis of valienamine in the microbial degradation of validamycin
      A after derivatization with p-nitrofluorobenzene by reversed-phase high
      performance liquid chromatography.
AB  - A reversed-phase high-performance liquid chromatography method for the
      quantitative analysis of valienamine in the microbial degradation of validamycin
      A, using a procedure for pre-column derivatization of valienamine with p
      nitrofluorobenzene is described. Valienamine in the broth was first isolated with
      the ion-exchange method. The optimized conditions for the derivatization were the
      reaction time 30 min and reaction temperature 100 degrees C. With the mobile
      phases consisting of acetonitrile-water (12:88) (eluent A) and methanol (eluent
      B), the gradient was carried out with 100% of A for 15 min and then 100% of B for
      another 10 min. The parameters in the process were the flow rate of the mobile
      phase 1.0 ml/min, the injection volume 20 microl, the column temperature 40
      degrees C and wavelength of ultraviolet detection 398 nm in all runs. A good
      linearity was found in the range of 0.5-150.0 microg/ml. Both intra- and inter
      day precisions of valienamine, expressed as the relative standard deviation, were
      less than 9.4%. Accuracy, expressed as the relative error, range from -0.5 to
      2.7%. The mean absolute recovery of valienamine at three different concentrations
      was 94.2%. The method was proved suitable for the study on the process of
      microbial degradation of validamycin A to produce valienamine.

PMID- 16095987
TI  - Assessment of 3-nitrobenzanthrone reductase activity in mammalian tissues by
      normal-phase HPLC with fluorescence detection.
AB  - 3-Nitrobenzanthrone (3-NBA) is a potent mutagen and possible human carcinogen
      present in diesel exhaust and airborne particulate matter. Nitroreduction is
      believed to play a crucial role in nitroarene activation and mutagenicity;
      however, quantification of nitroreduction rate in mammalian samples has proved
      difficult. In this study, we present a sensitive method to quantify 3
      nitrobenzanthrone reductase activity in murine tissues via normal-phase HPLC with
      fluorescence detection of the reduced product 3-aminobenzanthrone (3-ABA).
      Calibration linearity was obtained for pure 3-ABA concentrations of 1-500 ng/ml
      (r2>0.99), with a detection limit of 0.25 ng/ml (S/N=3). Incubation time,
      substrate concentration, and protein concentration in the reaction mixture were
      optimized, and the detection limit of the enzyme assay is 0.97 pmol/min/mg
      protein. The apparent K(m) and V(max) for post-mitochondrial supernatant from
      Mutatrade markMouse liver (i.e., liver S9) were 23.9 microM and 70.2 pmol/min/mg
      protein, respectively. Analysis of replicate samples of Mutatrade markMouse liver
      and lung S9 yielded mean activity values of 39.0+/-3.0 and 61.1+/-4.3
      pmol/min/mg, respectively. ANOVA revealed significant effects of tissue type and
      incubation condition (i.e., with or without N2). The results show significantly
      higher activity in lung, and, in contrast to that observed for 1-nitropyrene,
      incubation in open air (i.e., without N2 bubbling) causes only a marginal
      decrease in activity. Quantification of 3-NBA nitroreductase activity in murine
      tissues will provide insight into the published tissue-specific mutagenic
      activity of 3-NBA.

PMID- 16095988
TI  - Modifications of protein by polyunsaturated fatty acid ester peroxidation
      products.
AB  - The ability of unsaturated fatty acid methyl esters to modify bovine serum
      albumin (BSA) in the presence of a metal-catalyzed oxidation system [ascorbic
      acid/Fe (II)/O2] was investigated. The exposure of BSA to PUFA esters led to the
      generation of carbonyl groups and the formation of high-molecular-weight
      proteins, which were strongly dependent on the degree of fatty acid unsaturation.
      The high-molecular-weight proteins were detected by Western blot analysis and
      were not recognized by five antibodies. The observation that levels of conjugated
      dienes and malondialdehyde formed in the presence of BSA were substantially lower
      in the presence than in the absence of BSA indicated that radicals formed during
      the degradation of lipid hydroperoxides are likely involved in the formation of
      protein derivatives. These results may be important in understanding the specific
      roles of different polyunsaturated fatty acids in the pathophysiological effects
      associated with oxidative stress.

PMID- 16095998
TI  - Molecular mechanisms in gliomagenesis.
AB  - Glioma, and in particular high-grade astrocytoma termed glioblastoma multiforme
      (GBM), is the most common primary tumor of the brain. Primarily because of its
      diffuse nature, there is no effective treatment for GBM, and relatively little is
      known about the processes by which it develops. Therefore, in order to design
      novel therapies and treatments for GBM, research has recently intensified to
      identify the cellular and molecular mechanisms leading to GBM formation. Modeling
      of astrocytomas by genetic manipulation of mice suggests that deregulation of the
      pathways that control gliogenesis during normal brain development, such as the
      differentiation of neural stem cells (NSCs) into astrocytes, might contribute to
      GBM formation. These pathways include growth factor-induced signal transduction
      routes and processes that control cell cycle progression, such as the p16-CDK4-RB
      and the ARF-MDM2-p53 pathways. The expression of several of the components of
      these signaling cascades has been found altered in GBM, and recent data indicate
      that combinations of mutations in these pathways may contribute to GBM formation,
      although the exact mechanisms are still to be uncovered. Use of novel techniques
      including large-scale genomics and proteomics in combination with relevant mouse
      models will most likely provide novel insights into the molecular mechanisms
      underlying glioma formation and will hopefully lead to development of treatment
      modalities for GBM.

PMID- 16095999
TI  - Activation of AKT kinases in cancer: implications for therapeutic targeting.
AB  - The AKT1, AKT2, and AKT3 kinases have emerged as critical mediators of signal
      transduction pathways downstream of activated tyrosine kinases and
      phosphatidylinositol 3-kinase. An ever-increasing list of AKT substrates has
      precisely defined the multiple functions of this kinase family in normal
      physiology and disease states. Cellular processes regulated by AKT include cell
      proliferation and survival, cell size and response to nutrient availability,
      intermediary metabolism, angiogenesis, and tissue invasion. All these processes
      represent hallmarks of cancer, and a burgeoning literature has defined the
      importance of AKT alterations in human cancer and experimental models of
      tumorigenesis, continuing the legacy represented by the original identification
      of v-Akt as the transforming oncogene of a murine retrovirus. Many oncoproteins
      and tumor suppressors intersect in the AKT pathway, finely regulating cellular
      functions at the interface of signal transduction and classical metabolic
      regulation. This careful balance is altered in human cancer by a variety of
      activating and inactivating mechanisms that target both AKT and interrelated
      proteins. Reprogramming of this altered circuitry by pharmacologic modulation of
      the AKT pathway represents a powerful strategy for rational cancer therapy. In
      this review, we summarize a large body of data, from many types of cancer,
      indicating that AKT activation is one of the most common molecular alterations in
      human malignancy. We also review mechanisms of activation of AKT kinases,
      examples of therapeutic modulation of the AKT pathway in animal models, and the
      current status of efforts to target molecular components of the AKT pathway for
      cancer therapy and, possibly, cancer prevention.

PMID- 16096000
TI  - Mitochondria as functional targets of proteins coded by human tumor viruses.
AB  - Molecular analyses of tumor virus-host cell interactions have provided key
      insights into the genes and pathways involved in neoplastic transformation.
      Recent studies have revealed that the human tumor viruses Epstein-Barr virus
      (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), human papillomavirus
      (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-cell
      leukemia virus type 1 (HTLV-1) express proteins that are targeted to
      mitochondria. The list of these viral proteins includes BCL-2 homologues (BHRF1
      of EBV; KSBCL-2 of KSHV), an inhibitor of apoptosis (IAP) resembling Survivin
      (KSHV K7), proteins that alter mitochondrial ion permeability and/or membrane
      potential (HBV HBx, HPV E[wedge]14, HCV p7, and HTLV-1 p13(II)), and K15 of KSHV,
      a protein with undefined function. Consistent with the central role of
      mitochondria in energy production, cell death, calcium homeostasis, and redox
      balance, experimental evidence indicates that these proteins have profound
      effects on host cell physiology. In particular, the viral BCL-2 homologues BHRF1
      and KSBCL-2 inhibit apoptosis triggered by a variety of stimuli. HBx, p7,
      E1[wedge]4, and p13(II) exert powerful effects on mitochondria either directly
      due to their channel-forming activity or indirectly through interactions with
      endogenous channels. Further investigation of these proteins and their
      interactions with mitochondria will provide important insights into the
      mechanisms of viral replication and tumorigenesis and could aid in the discovery
      of new targets for anti-tumor therapy.

PMID- 16096001
TI  - Apoptotic pathways and therapy resistance in human malignancies.
AB  - Apoptosis and necrosis are two morphologically distinct forms of cell death that
      are important for maintaining of cellular homeostasis. Almost all agents can
      provoke either response when applied to cells; however, the duration of treatment
      and the dose of the used agents determine which type of death (apoptosis or
      necrosis) is initiated. The response of tumors to chemo-, radio-, and hormone
      therapy or to treatment with biologically active agents may depend at least in
      part on the propensity of these tumors to undergo cell death. Some tumors, e.g.,
      leukemias, small cell lung cancer, and seminomas, respond quickly to first-line
      therapy; this fast response is thought to result from induction of apoptosis.
      Solid tumors, on the other hand, usually respond slowly and less effectively,
      with cell death characterized not only by apoptosis but also by necrosis, or
      mitotic catastrophe. It is likely that resistance of tumors to treatment might be
      associated with defects in, or dysregulation of, different steps of the apoptotic
      pathways. Several attempts were undertaken to use the knowledge of these defects
      to design new drugs, which might either activate or re-activate the apoptotic
      machinery of tumor cells. Here we discuss the apoptotic pathways and their role
      in therapy resistance of human malignancies. Although such studies are still in
      progress, they offer great promise for future cancer therapy. We hope that some
      of these agents will turn out to be valuable additions to the future therapeutic
      arsenal, which will most probably include a combination of conventional cytotoxic
      drugs and molecular target-based pro-apoptotic drugs.

PMID- 16096002
TI  - Endostatin signaling and regulation of endothelial cell-matrix interactions.
AB  - The growth and survival of a malignant tumor are dependent on the formation and
      maintenance of its own microvasculature, a process termed angiogenesis.
      Inhibition of this phenomenon is an emerging strategy in cancer therapy. The
      extracellular matrix surrounding the vascular endothelial cells contains cryptic
      protein domains, which are exposed by changes in the proteolytic homeostasis of
      the tumor microenvironment. These fragments transmit local signals, which
      regulate vascular endothelial cell proliferation and migration. Endostatin, the
      proteolytic fragment of collagen type XVIII, is a potent inhibitor of tumor
      angiogenesis in various mouse models and is currently in clinical trials for
      therapeutic use in human cancer. Multiple cell surface receptors have been
      described for endostatin, but the signals transmitted by these receptors
      resulting in the inhibition of angiogenesis have so far been poorly
      characterized. Studies on the effects of endostatin on cultured endothelial cells
      suggest that the antimigratory and antiproliferative properties of this molecule
      are the major mechanisms underlying its antiangiogenic potential. These effects
      may be a consequence of endostatin modulation of endothelial cell-matrix
      interactions and pericellular proteolysis.

PMID- 16096003
TI  - A calcium-based theory of carcinogenesis.
AB  - Most human cancers are initiated by chronic injuries that repeatedly kill cells
      and must, therefore, repeatedly raise cell calcium within nearby survivors. They
      may also raise calcium in distant cells via calcium waves. Here it is argued that
      these calcium increases initiate oncogenesis by breaking gap junctions and thus
      disorganizing tissues and by activating proto-oncogenes. It is also argued that
      these calcium increases become self-perpetuating in part through the development
      of an ability of cells to divide in reduced extracellular calcium, i.e.,
      habituation to reduced extracellular calcium. I propose to test these calcium
      based theories by using aequorinated mice.

PMID- 16096005
TI  - The mechanism of naked DNA uptake and expression.
AB  - The administration of naked nucleic acids into animals is increasingly being used
      as a research tool to elucidate mechanisms of gene expression and the role of
      genes and their cognate proteins in the pathogenesis of disease in animal models
      (Herweijer and Wolff, 2003; Hodges and Scheule, 2003). It is also being used in
      several human clinical trials for genetic vaccines, Duchenne muscular dystrophy,
      peripheral limb ischemia, and cardiac ischemia (Davis et al., 1996; Romero et
      al., 2002; Tsurumi et al., 1997). Naked DNA is an attractive non-viral vector
      because of its inherent simplicity and because it can easily be produced in
      bacteria and manipulated using standard recombinant DNA techniques. It shows very
      little dissemination and transfection at distant sites following delivery and can
      be readministered multiple times into mammals (including primates) without
      inducing an antibody response against itself (i.e., no anti-DNA antibodies
      generated) (Jiao et al., 1992). Also, contrary to common belief, long-term
      foreign gene expression from naked plasmid DNA (pDNA) is possible even without
      chromosome integration if the target cell is postmitotic (as in muscle) or slowly
      mitotic (as in hepatocytes) and if an immune reaction against the foreign protein
      is not generated (Herweijer et al., 2001; Miao et al., 2000; Wolff et al., 1992;
      Zhang et al., 2004). With the advent of intravascular and electroporation
      techniques, its major restriction--poor expression levels--is no longer limiting
      and levels of foreign gene expression in vivo are approaching what can be
      achieved with viral vectors. Direct in vivo gene transfer with naked DNA was
      first demonstrated when efficient transfection of myofibers was observed
      following injection of mRNA or pDNA into skeletal muscle (Wolff et al., 1990). It
      was an unanticipated finding in that the use of naked nucleic acids was the
      control for experiments designed to assess the ability of cationic lipids to
      mediate expression in vivo. Subsequent studies also found foreign gene expression
      after direct injection in other tissues such as heart, thyroid, skin, and liver
      (Acsadi et al., 1991; Hengge et al., 1996; Kitsis and Leinwand, 1992; Li et al.,
      1997; Sikes and O'Malley 1994; Yang and Huang, 1996). However, the efficiency of
      gene transfer into skeletal muscle and these other tissues by direct injection is
      relatively low and variable, especially in larger animals such as nonhuman
      primates (Jiao et al., 1992). After our laboratory had developed novel
      transfection complexes of pDNA and amphipathic compounds and proteins, we sought
      to deliver them to hepatocytes in vivo via an intravascular route into the portal
      vein. Our control for these experiments was naked pDNA and we were once again
      surprised that this control group had the highest expression levels (Budker et
      al., 1996; Zhang et al., 1997). High levels of expression were achieved by the
      rapid injection of naked pDNA in relatively large volumes via the portal vein,
      the hepatic vein, and the bile duct in mice and rats. The procedure also proved
      effective in larger animals such as dogs and nonhuman primates (Eastman et al.,
      2002; Zhang et al., 1997). The next major advance was the demonstration that high
      levels of expression could also be achieved in hepatocytes in mice by the rapid
      injection of naked DNA in large volumes simply into the tail vein (Liu et al.,
      1999; Zhang et al., 1999). This hydrodynamic tail vein (HTV) procedure is proving
      to be a very useful research tool not only for gene expression studies, but also
      more recently for the delivery of small interfering RNA (siRNA) (Lewis et al.,
      2002; McCaffrey et al., 2002). The intravascular delivery of naked pDNA to muscle
      cells is also attractive particularly since many muscle groups would have to be
      targeted for intrinsic muscle disorders such as Duchenne muscular dystrophy. High
      levels of gene expression were first achieved by the rapid injection of naked DNA
      in large volumes via an artery route with both blood inflow and outflow blocked
      surgically (Budker et al., 1998; Zhang et al., 2001). Intravenous routes have
      also been shown to be effective (Hagstrom et al., 2004; Liang et al., 2004; Liu
      et al., 2001). For limb muscles, the ability to use a peripheral limb vein for
      injection and a proximal, external tourniquet to block blood flow renders the
      procedure to be clinically viable. This review concerns itself with the mechanism
      by which naked DNA is taken up by cells in vivo. A greater understanding of the
      mechanisms involved in the uptake and expression of naked DNA, and thus
      connections between postulated mechanisms and expression levels, is emphasized.
      Inquiries into the mechanism not only aid these practical efforts, but are also
      interesting on their own account with relevance to viral transduction and
      cellular processes. The delivery to hepatocytes is first discussed given the
      greater information available for this process, and then uptake by myofibers is
      discussed.

PMID- 16096006
TI  - Targeted delivery of therapeutic oligonucleotides to pulmonary circulation.
AB  - Functional oligodeoxynucleotides (ODN) such as antisense ODN (AS-ODN) show
      promise as new therapeutics for the treatment of a number of pulmonary diseases.
      They also hold potential to serve as a research tool for the study of gene
      function related to lung physiology. The success of their application is largely
      dependent on the development of an efficient delivery vehicle. This chapter
      summarizes work toward the development of lipidic vectors for targeted ODN
      delivery to pulmonary circulation. Recent advancements in the development of
      novel ODN are also discussed briefly.

PMID- 16096007
TI  - Naked DNA for liver gene transfer.
AB  - The majority of acquired and inherited genetic disorders, including most inborn
      errors of metabolism, are manifested in the liver. Therefore, it is hardly any
      surprise to see a large number of Medline reports describing gene therapy efforts
      in preclinical settings directed toward this organ (Inoue et al., 2004; Oka and
      Chen, 2004). Of late, non-viral vectors have garnered a lot of attention from the
      biomedical research community engaged in liver gene therapy (Gupta et al., 2004).
      However, the first initiative toward gene transfer to the liver using a non-viral
      approach was taken by Hickman et al. (1994), who applied the technique of naked
      DNA injection pioneered by Wolff (1990) for skeletal muscle. Direct injection of
      naked DNA resulted in low, variable and localized gene expression in the rat
      liver. Consequently, several developments reported in the literature since then
      aimed to improve hepatic gene expression by employing both surgical and
      nonsurgical methods. These developments include the exploitation of the unique
      vasculature of liver as well as the use of electric and mechanical force as an
      adjunct to the systemic administration of the naked plasmid gene. This chapter
      focuses on these developments reported from various laboratories, including ours.
      In addition, the underlying mechanism responsible for the dramatic increase in
      gene expression using these latest approaches for non-viral gene transfer to the
      liver is also discussed.

PMID- 16096008
TI  - Hydrodynamic delivery.
AB  - Hydrodynamic delivery has emerged as a near-perfect method for intracellular DNA
      delivery in vivo. For gene delivery to parenchymal cells, only essential DNA
      sequences need to be injected via a selected blood vessel, eliminating safety
      concerns associated with current viral and synthetic vectors. When injected into
      the bloodstream, DNA is capable of reaching cells in the different tissues
      accessible to the blood. Hydrodynamic delivery employs the force generated by the
      rapid injection of a large volume of solution into the incompressible blood in
      the circulation to overcome the physical barriers of endothelium and cell
      membranes that prevent large and membrane-impermeable compounds from entering
      parenchymal cells. In addition to the delivery of DNA, this method is useful for
      the efficient intracellular delivery of RNA, proteins, and other small compounds
      in vivo. This review discusses the development, current application, and clinical
      potential of hydrodynamic delivery.

PMID- 16096009
TI  - Electric pulse-mediated gene delivery to various animal tissues.
AB  - Electroporation designates the use of electric pulses to transiently permeabilize
      the cell membrane. It has been shown that DNA can be transferred to cells through
      a combined effect of electric pulses causing (1) permeabilization of the cell
      membrane and (2) an electrophoretic effect on DNA, leading the polyanionic
      molecule to move toward or across the destabilized membrane. This process is now
      referred to as DNA electrotransfer or electro gene transfer (EGT). Several
      studies have shown that EGT can be highly efficient, with low variability both in
      vitro and in vivo. Furthermore, the area transfected is restricted by the
      placement of the electrodes, and is thus highly controllable. This has led to an
      increasing use of the technology to transfer reporter or therapeutic genes to
      various tissues, as evidenced from the large amount of data accumulated on this
      new approach for non-viral gene therapy, termed electrogenetherapy (EGT as well).
      By transfecting cells with a long lifetime, such as muscle fibers, a very long
      term expression of genes can be obtained. A great variety of tissues have been
      transfected successfully, from muscle as the most extensively used, to both soft
      (e.g., spleen) and hard tissue (e.g., cartilage). It has been shown that
      therapeutic levels of systemically circulating proteins can be obtained, opening
      possibilities for using EGT therapeutically. This chapter describes the various
      aspects of in vivo gene delivery by means of electric pulses, from important
      issues in methodology to updated results concerning the electrotransfer of
      reporter and therapeutic genes to different tissues.

PMID- 16096010
TI  - In vivo application of RNA interference: from functional genomics to
      therapeutics.
AB  - RNAi has rapidly become a powerful tool for drug target discovery and validation
      in cell culture, and now has largely displaced efforts with antisense and
      ribozymes. Consequently, interest is rapidly growing for extension of its
      application to in vivo systems, such as animal disease models and human
      therapeutics. Studies on RNAi have resulted in two basic methods for its use for
      gene selective inhibition: 1) cytoplasmic delivery of short dsRNA
      oligonucleotides (siRNA), which mimics an active intermediate of an endogenous
      RNAi mechanism and 2) nuclear delivery of gene expression cassettes that express
      a short hairpin RNA (shRNA), which mimics the micro interfering RNA (miRNA)
      active intermediate of a different endogenous RNAi mechanism. Non-viral gene
      delivery systems are a diverse collection of technologies that are applicable to
      both of these forms of RNAi. Importantly, unlike antisense and ribozyme systems,
      a remarkable trait of siRNA is a lack of dependence on chemical modifications
      blocking enzymatic degradation, although chemical protection methods developed
      for the earlier systems are being incorporated into siRNA and are generally
      compatible with non-viral delivery systems. The use of siRNA is emerging more
      rapidly than for shRNA, in part due to the increased effort required to construct
      shRNA expression systems before selection of active sequences and verification of
      biological activity are obtained. In contrast, screens of many siRNA sequences
      can be accomplished rapidly using synthetic oligos. It is not surprising that the
      use of siRNA in vivo is also emerging first. Initial in vivo studies have been
      reported for both viral and non-viral delivery but viral delivery is limited to
      shRNA. This review describes the emerging in vivo application of non-viral
      delivery systems for RNAi for functional genomics, which will provide a
      foundation for further development of RNAi therapeutics. Of interest is the rapid
      adaptation of ligand-targeted plasmid-based nanoparticles for RNAi agents. These
      systems are growing in capabilities and beginning to pose a serious rival to
      viral vector based gene delivery. The activity of siRNA in the cytoplasm may
      lower the hurdle and thereby accelerate the successful development of
      therapeutics based on targeted non-viral delivery systems.

PMID- 16096011
TI  - A novel gene expression system: non-viral gene transfer for hemophilia as model
      systems.
AB  - It is highly desirable to generate tissue-specific and persistently high-level
      transgene expression per genomic copy from gene therapy vectors. Such vectors can
      reduce the cost and preparation of the vectors and reduce possible host immune
      responses to the vector and potential toxicity. Many gene therapy vectors have
      failed to produce therapeutic levels of transgene because of inefficient
      promoters, loss of vector or gene expression from episomal vectors, or a
      silencing effect of integration sites on integrating vectors. Using in vivo
      screening of vectors incorporating many different combinations of gene regulatory
      sequences, liver-specific, high-expressing vectors to accommodate factor IX,
      factor VIII, and other genes for effective gene transfer have been established.
      Persistent and high levels of factor IX and factor VIII gene expression for
      treating hemophilia B and A, respectively, were achieved in mouse livers using
      hydrodynamics-based gene transfer of naked plasmid DNA incorporating these novel
      gene expression systems. Some other systems to prolong or stabilize the gene
      expression following gene transfer are also discussed.

PMID- 16096012
TI  - Site-specific integration with phiC31 integrase for prolonged expression of
      therapeutic genes.
AB  - Need of a site-specific integrating vector in gene therapy has become pressing,
      as recent work has shown that many of the current integrating vectors used
      preferentially integrate in the vicinity of genes. A site-specific integrating
      vector would reduce the risk of insertional mutagenesis posed by randomly
      integrating vectors, and a non-viral vector would reduce the safety and
      immunogenicity problems associated with viral vectors. The phiC31 integrase is a
      protein from Streptomyces phage phiC31 that has been developed as a non-viral
      site-specific gene therapy vector. The phiC31 integrase catalyzes the integration
      of a plasmid containing attB into pseudo attP sites in mammalian genomes. It has
      been shown to function in tissue culture cells as well as in mice. Vectors based
      on the phiC31 integrase were able to treat tyrosinemia type I in a mouse model
      and two forms of epidermolysis bullosa in keratinocytes from patients,
      demonstrating its effectiveness as a gene therapy vector. Development of phiC31
      integrase-based vectors is still underway, but it has already been shown to
      provide long-term expression through site-specific integration.

PMID- 16096013
TI  - Sleeping beauty transposon-mediated gene therapy for prolonged expression.
AB  - The Sleeping Beauty (SB) transposon system represents a new vector for non-viral
      gene transfer that melds advantages of viruses and other forms of naked DNA
      transfer. The transposon itself is comprised of two inverted terminal repeats of
      about 340 base pairs each. The SB system directs precise transfer of specific
      constructs from a donor plasmid into a mammalian chromosome. The excision of the
      transposon from a donor plasmid and integration into a chromosomal site is
      mediated by Sleeping Beauty transposase, which can be delivered to cells vita its
      gene or its mRNA. As a result of its integration in chromosomes, and its lack of
      viral sequences that are often detected by poorly understood cellular defense
      mechanisms, a gene in a chromosomally integrated transposon can be expressed over
      the lifetime of a cell. SB transposons integrate nearly randomly into chromosomes
      at TA-dinucleotide base pairs although the sequences flanking the TAs can
      influence the probability of integration at a given site. Although random
      integration of vectors into human genomes is often thought to raise significant
      safety issues, evidence to date does not indicate that random insertions of SB
      transposons represent risks that are equal to those of viral vectors. Here we
      review the activities of the SB system in mice used as a model for human gene
      therapy, methods of delivery of the SB system, and its efficacy in ameliorating
      disorders that model human disease.

PMID- 16096014
TI  - Cancer-specific gene therapy.
AB  - Cancer cells transcriptionally activate many genes that are important for
      uncontrolled proliferation and cell death. Deregulated transcriptional machinery
      in tumor cells usually consists of increased expression/activity of transcription
      factors. Ideally, cancer-specific killing can be achieved by delivering a
      therapeutic gene under the control of the DNA elements that can be activated by
      transcription factors that are overexpressed and/or constitutively activated in
      cancer cells. Additionally, tumor-specific translation of tumor-killing genes has
      been also exploited in cancer gene therapy. Based on these rationales, cancer
      specific expression of a therapeutic gene has emerged as a potentially successful
      approach for cancer gene therapy. To achieve tumor-specific expression, cancer
      specific vectors are generally composed of promoters, enhancers, and/or 5'-UTR
      that are responsive to tumor-specific transcription factors. A number of cancer
      specific promoters have been reported, such as those of probasin, human
      telomerase reverse transcriptase, survivin, ceruloplasmin, HER-2, osteocalcin,
      and carcinoembryonic antigen. Evidences suggest that the enhancer element
      targeted by beta-catenin can be useful to target colon cancer cells. The 5'-UTR
      of the basic fibroblast growth factor-2 has been reported to provide tumor
      specificity. Moreover, a variety of therapeutic genes demonstrated direct
      antitumor effects such as those encoding proapoptotic proteins p53, E1A, p202,
      PEA3, BAX, Bik, and prodrug metabolizing enzymes, namely thymidine kinase and
      cytosine deaminase. As cancerous cells of different origins vary significantly in
      their genetic, transcriptional/translational, and cellular profiles, the success
      of a cancer gene therapy will not be promised unless it is carefully designed
      based on the biology of a specific tumor type. Thus, tremendous research efforts
      have been focused on the development of non-viral vectors that selectively target
      various tumors resulting in minimal toxicity in the normal tissues. Significant
      progresses were also made in the exploitation of various novel apoptotic,
      cytotoxic genes as therapeutic tools that suppress the growth of different
      tumors. Together, these recent advances provide rationales for future clinical
      testing of transcriptionally targeted non-viral vectors in cancer patients.

PMID- 16096015
TI  - DNA vaccine.
AB  - The DNA vaccine has proven to be one of the most promising applications in the
      field of gene therapy. Due to its unique ability to readily induce humoral as
      well as cellular immune responses, it attracted great interest when the concept
      was first confirmed in the early 1990s. After thousands of articles related to
      the DNA vaccine were published, scientists began to realize that although the DNA
      vaccine is very effective in small animal models, its effectiveness in recent
      clinical trails is rather disappointing. Therefore, current effort has been
      shifted to understanding the different performance of the DNA vaccine in mouse
      and large animal models and on how to transfer the success of the DNA vaccine in
      small animals to large animals and humans.

PMID- 16096016
TI  - Airway gene therapy.
AB  - Given both the accessibility and the genetic basis of several pulmonary diseases,
      the lungs and airways initially seemed ideal candidates for gene therapy. Several
      routes of access are available, many of which have been refined and optimized for
      nongene drug delivery. Two respiratory diseases, cystic fibrosis (CF) and alpha1
      antitrypsin (alpha1-AT) deficiency, are relatively common; the single gene
      responsible has been identified and current treatment strategies are not
      curative. This type of inherited disease was the obvious initial target for gene
      therapy, but it has become clear that nongenetic and acquired diseases, including
      cancer, may also be amenable to this approach. The majority of preclinical and
      clinical studies in the airway have involved viral vectors, although for diseases
      such as CF, likely to require repeated application, non-viral delivery systems
      have clear advantages. However, with both approaches a range of barriers to gene
      expression have been identified that are limiting success in the airway and
      alveolar region. This chapter reviews these issues, strategies aimed at
      overcoming them, and progress into clinical trials with non-viral vectors in a
      variety of pulmonary diseases.

PMID- 16096017
TI  - Non-viral vector as vaccine carrier.
AB  - Over the last several years, advances in gene-based delivery technology arising
      from the field of gene therapy have helped revitalize the field of vaccine
      development. Genetic vaccination encoding antigen from bacteria, virus, and
      cancer has shown promise in protective humoral and cellular immunity; however,
      the potential disadvantages of naked DNA vaccine have reduced the value of the
      approach. To optimize antigen delivery efficiency as well as vaccine efficacy,
      the non-viral vector as vaccine carrier, for example, the cationic liposome, has
      shown particular benefits to circumvent the obstacles that both peptide/protein-
      and gene-based vaccines have encountered. Liposome-mediated vaccine delivery
      provides greater efficacy and safer vaccine formulation for the development of
      vaccine for human use. The success of the liposome-based vaccine has been
      demonstrated in clinical trials and further human trials are also in progress.

PMID- 16096018
TI  - Non-viral vectors for gene therapy: clinical trials in cardiovascular disease.
AB  - The population of patients with end-stage symptomatic coronary and peripheral
      vascular disease is ever-expanding. Many of these patients no longer have options
      for mechanical revascularization, and despite maximal medical therapy, they
      remain physically limited due to angina or critical limb ischemia. The
      fundamental problem in these patients is insufficient blood supply to muscle due
      to severely diseased conduit vessels to the target tissue. Therefore, it seems
      logical that increasing the blood supply to ischemic tissue will relieve
      symptoms. One potential means to achieving this goal is via therapeutic
      angiogenesis. The molecular mechanisms behind vascular development are being
      elucidated, and animal models have shown that mediators of vascular development
      can be harnessed to produce new capillaries in ischemic tissue. These mediators
      include cytokines such as vascular endothelial growth factor (VEGF) and
      fibroblast growth factor (FGF). Angiogenic cytokines can be delivered in several
      forms including recombinant protein or via gene delivery as a naked plasmid or
      via viral vector. This chapter will describe the clinical trial experience to
      date with delivery of non-viral gene therapy for therapeutic angiogenesis in
      humans with disabling myocardial ischemia and peripheral vascular disease.

PMID- 16096020
TI  - Section I. The cholinergic system.

PMID- 16096021
TI  - Section II. The dopamine system.

PMID- 16096022
TI  - Section III. The norepinephrine system.

PMID- 16096023
TI  - Section IV. The adrenaline system.

PMID- 16096024
TI  - Section V. Serotonin system.

PMID- 16096025
TI  - Section VI. Conclusion.

PMID- 16096026
TI  - Genetic switches during bacteriophage lambda development.

PMID- 16096027
TI  - Molecular aspects of meiotic chromosome synapsis and recombination.

PMID- 16096028
TI  - Non-HKD phospholipase D enzymes: new players in phosphatidic acid signaling?

PMID- 16096029
TI  - Nucleotide excision repair.

PMID- 16096030
TI  - Signal transduction pathways in cancer development and as targets for cancer
      prevention.

PMID- 16096031
TI  - ADAR gene family and A-to-I RNA editing: diverse roles in posttranscriptional
      gene regulation.

PMID- 16096032
TI  - The second paradigm for activation of transcription.

PMID- 16096033
TI  - Families of protein phosphatase 1 modulators activated by protein kinases a and
      C: focus on brain.

PMID- 16096034
TI  - Transparency of research methods: proud to be a Naked Emperor.

PMID- 16096036
TI  - The Nordic Back Pain Subpopulation Program: validation and improvement of a
      predictive model for treatment outcome in patients with low back pain receiving
      chiropractic treatment.
AB  - OBJECTIVE: The aim of this study was to develop a predictive model for treatment
      outcome in patients with low back pain (LBP) receiving chiropractic treatment.
      METHODS: This multicenter practice-based predictive validity study was conducted
      in private chiropractic practices in Sweden. Of 64 previously compliant
      chiropractors, 58 recruited a maximum of 30 consecutive patients with LBP each.
      Information was provided on 1061 patients, of which 1057 questionnaires were
      valid. Chiropractic treatment was decided by the treating chiropractor. The
      outcome variable was the self-reported "definite improvement" at the fourth
      visit. The predictor variables included model 1, 3 hypothesized prognostic groups
      (best, intermediate, and least favorable) based on clinical information collected
      at baseline and at the second visit; and 4 additional models based on the
      following variables: age, sex, pain intensity during past 24 hours, description
      of disability, duration and pattern of pain during present attack, total duration
      of pain, and pain pattern during the past 12 months. RESULTS: Three of our
      factors were best at predicting the absence of improvement by the fourth visit
      and were able to correctly classify 79% of patients and to cover 74% of the
      receiver operated characteristics curve. These were (1) no definite overall
      improvement by the second treatment, (2) presence of leg pain, and (3) the
      minimum total duration of pain over the last 12 months being 30 days. CONCLUSION:
      In this study, patients with LBP who also had leg pain and LBP occurring
      sufficiently frequently or having lasted sufficiently long to add up to at least
      30 days in the past year, and who did not report definite general improvement by
      the second treatment were not good candidates for short-term recovery. It is
      suggested that patients who fit the criteria of potential nonresponders should be
      carefully monitored to allow a selective approach of care.

PMID- 16096037
TI  - Implications for the use of postural analysis as a clinical diagnostic tool:
      reliability of quantifying upright standing spinal postures from photographic
      images.
AB  - OBJECTIVES: A repeated measures design was used to test the reliability of
      standing spine postures within subjects using a biologically relevant measure
      determined by digitization of images and to compare the results to a previously
      tested vertical reference method. METHODS: Twenty subjects attended 3 sessions
      consisting of 5 trials each. Photographs of the sagittal and posterior views of
      normal upright standing were taken. Landmarks were digitized and cervical,
      thoracic, and lumbar spinal angles were calculated using the algebraic dot
      product. Intraclass correlation coefficients were used to evaluate intrasubject
      reliability across sessions. RESULTS: According to the intraclass correlation
      coefficients, posture had good to excellent reliability in the sagittal view and
      provided a more stable measure of spinal angles than the posterior view. Mean
      repositioning errors were less than 6 degrees and 2 degrees in the sagittal and
      posterior views, respectively. CONCLUSIONS: Although the repeatability of posture
      was improved in the sagittal view, when a biological measure was used instead of
      an external vertical reference to calculate spinal angles, individual subject
      posture was still variable. This brings into question the effectiveness and
      validity of using surface skin markers to track postural changes due to clinical
      interventions. If the postural analysis approach is to be used to detect changes
      due to clinical treatment, such changes must be larger than the baseline
      repositioning errors seen in healthy subjects.

PMID- 16096038
TI  - Cervical muscle response to head rotation in whiplash-type right lateral impacts.
AB  - OBJECTIVE: To determine the electromyogram (EMG) response of the cervical muscles
      to a right lateral impact whiplash-type perturbation when the head is rotated.
      METHODS: Twenty healthy volunteers were subjected to right lateral impacts of
      4.2, 8.1, 10.3, and 12.5 m/s2 and were looking either left or right. Bilateral
      EMGs of the sternocleidomastoid, trapezius, and splenius capitis muscles were
      recorded. Triaxial accelerometers recorded the acceleration of the chair, torso
      at the shoulder level, and head of the participant. RESULTS: In a right lateral
      impact, muscle responses were of low magnitude with the head rotated to either
      the left or the right. At the highest acceleration of 12.5 m/s2, all generated
      less than 39% of their maximal voluntary contraction EMG. The sternocleidomastoid
      muscle showed a greater EMG response than its counterpart and the muscles
      contralateral to the direction of impact had higher EMG responses. The time to
      onset of the EMG for the splenii capitis and trapezii generally decreased with
      increasing levels of acceleration. As anticipated, an increase in applied
      acceleration resulted in an increase in accompanying head accelerations (P <
      .05), and when the head acceleration increased, so too did the force equivalent
      exertions by the various muscles. CONCLUSIONS: Overall, a right lateral impact
      with head rotation to either right or left appears to reduce the activity and
      thus the risk of muscle injury, perhaps because of "bracing" by muscles actively
      producing rotation or because of greater spinal stability from other structures
      when the head is in the rotated position.

PMID- 16096039
TI  - Translation and validation of the danish version of the Bournemouth
      questionnaire.
AB  - OBJECTIVE: Translation, cultural adaptation, and validation of the Danish version
      of the Bournemouth Questionnaire (BQ). METHODS: Translation/retranslation of the
      English version of the BQ was done blindly and independently by 4 different
      individuals and adapted by an expert team. The Danish version of the BQ was
      tested for face validity in a sample of low-back pain (LBP) patients attending 2
      chiropractic clinics. Reproducibility was tested using 28 stable LBP patients
      attending a hospital outpatient back-pain clinic. Finally, the Danish version of
      the BQ was tested for external construct validity, external longitudinal
      construct validity, internal consistency, and sensitivity to change against the
      Danish versions of the SF-36 and the Roland-Morris Disability Questionnaire
      (RMDQ) using 118 first-time LBP patients reporting to 1 of 7 chiropractic
      clinics. RESULTS: Minor changes were made after the face-validity test.
      Intraclass correlation coefficient of the total score for the BQ based on the 2
      administrations was 0.96. Satisfactory values for the external construct validity
      and the external longitudinal construct validity were found using both Pearson r
      and Bland-Altman plots. Cronbach alpha's were .89 and .88 for the pretreatment
      and posttreatment scores, respectively. The Danish version of the BQ showed
      greater responsiveness than the SF-36 and similar responsiveness when compared
      with the RMDQ. CONCLUSIONS: The BQ was successfully translated and culturally
      adapted into Danish. The BQ was successfully tested for validity, consistency,
      and responsiveness against the Danish version of the SF-36 and RMDQ.

PMID- 16096040
TI  - Interobserver reliability of neck-mobility measurement by means of the flock-of
      birds electromagnetic tracking system.
AB  - OBJECTIVE: To establish the interobserver reliability for measuring neck mobility
      in human subjects by means of an electromagnetic tracking device, the Flock-of
      Birds system. METHODS: Two observers independently and in random order assessed
      the cervical range-of-motion in 30 subjects with a dysfunction in the neck and
      shoulder region (symptomatic subjects) and 30 subjects without known pathology
      (asymptomatic subjects). Measurements included rotation in neutral position, in
      flexed position and in extended position, flexion-extension, and lateral bending
      (all active and passive). Reliability was analyzed by intraclass correlation
      coefficient (ICC) and agreement by limits of agreement and percentage of paired
      observations within 5 degrees, 10 degrees, and 15 degrees. RESULTS: For
      asymptomatic subjects, the ICC varied from 0.57 to 0.85, and the limits of
      agreement varied between 14.5 degrees and 27.0 degrees. The percentage of paired
      observations within 5 degrees, 10 degrees, and 15 degrees ranged from 31% to 57%,
      58% to 90%, and 78% to 93%, respectively. For symptomatic subjects, the ICC
      varied from 0.36 to 0.91, and the limits of agreement varied between 9.6 degrees
      and 37.8 degrees. The percentage of paired observations within 5 degrees, 10
      degrees, and 15 degrees ranged from 17% to 60%, 33% to 93%, and 50% to 97%,
      respectively. CONCLUSIONS: Despite the use of a standardized protocol and a
      sophisticated measurement system, the interobserver reliability of neck mobility
      was variable in quality, with reliability being good in rotation in neutral
      position, flexion-extension, and lateral bending.

PMID- 16096041
TI  - Comparison of mechanical force of manually assisted chiropractic adjusting
      instruments.
AB  - OBJECTIVE: To quantify the force-time and force-delivery characteristics of six
      commonly used handheld chiropractic adjusting devices. METHODS: Four spring
      loaded instruments, the Activator Adjusting Instrument; Activator II Adjusting
      Instrument, Activator III Adjusting Instrument, and Activator IV Adjusting
      Instrument, and two electromechanical devices, the Harrison Handheld Adjusting
      Instrument and Neuromechanical Impulse Adjusting Instrument, were applied to a
      dynamic load cell. A total of 10 force-time histories were obtained at each of
      three force excursion settings (minimum to maximum) for each of the six adjusting
      instruments at preload of approximately 20 N. RESULTS: The minimum-to-maximum
      force excursion settings for the spring-loaded mechanical adjusting instruments
      produced similar minimum-to-maximum peak forces that were not appreciably
      different for most excursion settings. The electromechanical adjusting
      instruments produced short duration ( approximately 2-4 ms), with more linear
      minimum-to-maximum peak forces. The force-time profile of the electromechanical
      devices resulted in a more uniform and greater energy dynamic frequency response
      in comparison to the spring-loaded mechanical adjusting instruments. CONCLUSIONS:
      The handheld, electromechanical instruments produced substantially larger peak
      forces and ranges of forces in comparison to the handheld, spring-loaded
      mechanical devices. The electromechanical instruments produced greater dynamic
      frequency area ratios than their mechanical counterparts. Knowledge of the force
      time history and force-frequency response characteristics of spinal manipulative
      instruments may provide basic benchmarks and may assist in understanding
      mechanical responses in the clinical setting.

PMID- 16096042
TI  - Implementation of a course on wellness concepts into a chiropractic college
      curriculum.
AB  - OBJECTIVE: The purpose of this study is to implement and evaluate a course on
      "wellness concepts" for chiropractic students, emphasizing national goals and
      evidence-based practices for health promotion and prevention. METHODS: Teaching
      methods included traditional lecture discussions and experiential activities,
      including objectives described in Healthy People 2010. Evaluation included pre-
      and posttests of students' familiarity with and intention to use key concepts,
      resources, and practices; item analysis of multiple choice exams; and a
      qualitative survey. RESULTS: Increases in students' self-reported familiarity
      were statistically significant for all but 2 of the 23 key topics assessed. At
      baseline, students already expressed intention to use most wellness-related
      practices listed, and showed significant increases for approximately half the
      practices listed at the posttest. Item analysis found students less able to
      correctly answer questions requiring analytic thinking than simple memorization.
      Students were most satisfied with the experiential portions of the course.
      CONCLUSION: Although the course was successful at introducing students to
      national resources and initiatives related to wellness, health promotion, and
      prevention, these concepts may be more meaningful if integrated into a teaching
      clinic that encouraged practical application of course concepts.

PMID- 16096043
TI  - High-velocity low-amplitude spinal manipulation for symptomatic lumbar disk
      disease: a systematic review of the literature.
AB  - OBJECTIVE: The aim of the study was to review the evidence for high-velocity low
      amplitude spinal manipulation (HVLASM) for symptomatic lumbar disk disease
      (SLDD). METHODS: A systematic review of the literature was performed. The
      Cochrane Central Register of Controlled Trials, Medline, Cumulative Index to
      Nursing and Allied Health Literature, and Mantis were searched. Evidence-based
      operational definitions of SLDD, HVLASM, and outcomes measures were established.
      Articles were assessed using these inclusion criteria: (1) published in English,
      (2) measured at least one outcome in subjects with SLDD undergoing HVLASM, (3)
      descriptions were sufficiently clear to meet all 3 categories of our operational
      definitions. Articles that met the inclusion criteria were assessed by 2
      independent reviewers and assigned quality ratings based on previously published
      guidelines. RESULTS: Sixteen studies met the inclusion criteria, representing 203
      total subjects. Of these, 172 subjects received HVLASM as active treatment, and
      31 received other treatments as comparison subjects. Improvements in patient
      based and physiological outcomes were reported among subjects receiving HVLASM;
      however, no conclusions regarding safety and effectiveness could be drawn from
      this review because the overall body of evidence uncovered was lacking in quality
      and quantity. CONCLUSION: HVLASM for SLDD has been reasonably described in the
      literature; however, the evidence is limited, and definitive conclusions on
      safety and effectiveness cannot be made at this time. The reviewed evidence
      supports the hypothesis that HVLASM may be effective in the treatment of SLDD and
      does not support the hypothesis that HVLASM is inherently unsafe in SLDD cases.
      It appears that patients with lumbar disk pathology do undergo manipulative
      treatment in practice. Consequently, this should be an area of research
      importance. More high-quality clinical trials using valid and reliable diagnostic
      criteria and outcomes measures are needed.

PMID- 16096044
TI  - A systematic review of conservative treatments for acute neck pain not due to
      whiplash.
AB  - OBJECTIVE: To identify the evidence base of clinical trials of conservative
      treatments for acute neck pain not due to whiplash injury. DESIGN AND SETTING: A
      comprehensive literature search was performed in MEDLINE, CINHAHL, AMED, MANTIS,
      Index to Chiropractic Literature, Alt HealthWatch, the Cochrane Database of
      Systematic Reviews, the Cochrane Controlled Trials Registry, and several EBSCO
      Information Services databases. Systematic retrieval and evaluation procedures
      were used. RESULTS: The search generated 1980 citations. Four trials (5
      publications) were accepted according to the inclusion/exclusion criteria. Three
      trials used a form of spinal manual therapy. One of these trials used only one
      manipulation and reported immediate effects on pain, with real manipulation
      producing significantly greater pain reduction than control procedure. The other
      2 of these trials reported on outcomes over 1 to 3 weeks. In 1 trial, the group
      receiving manipulation showed significantly greater pain reduction at 1 week than
      did the group receiving only medication. In the other trial, the group receiving
      transcutaneous electrical nerve stimulation had a significantly greater level of
      pain reduction at 3 weeks. In the fourth trial, exercise was compared to passive
      physiotherapy; however, outcomes were not reported until 6 and 12 months, so the
      results cannot be compared to the natural history of acute neck pain not due to
      whiplash. CONCLUSION: There is limited evidence of the benefit of spinal
      manipulation and transcutaneous electrical nerve stimulation in the treatment of
      acute neck pain not due to whiplash injury. There is a dearth of high-quality
      clinical trials of conservative treatments for this condition.

PMID- 16096045
TI  - Symptomatic herniation pit of the femoral neck: a case report.
AB  - OBJECTIVE: To discuss herniation pits of the femoral neck as a possible source of
      hip pain in a young athletic population. CLINICAL FEATURES: A 25-year-old former
      varsity volleyball player sought treatment for recurrent episodes of sharp left
      hip pain after intense physical activity. Radiographs revealed a small, oval,
      lobulated radiolucency with a thin sclerotic border in the superolateral aspect
      of the left femoral neck. Passive internal rotation of the left hip reproduced
      the complaint. Iliopsoas tendinitis/bursitis tests did not reproduce the
      complaint. INTERVENTION AND OUTCOME: The patient reported no significant
      reduction of hip pain after a variety of conservative therapies including soft
      tissue therapy, stretching, interferential current, and long-axis distraction.
      CONCLUSION: There is evidence to suggest that herniation pits of the femoral neck
      are a result of mechanical stress from the overlying joint capsule and iliopsoas
      tendon. Herniation pits of the femoral neck should be considered a potential
      cause of hip pain, particularly if the patient is physically active.

PMID- 16096046
TI  - Conservative treatment of a patient with syringomyelia using chiropractic
      biophysics protocols.
AB  - OBJECTIVE: To present a case of a 41-year-old man with syringomyelia and
      intractable pain and the subsequent reduction of symptoms. CLINICAL FEATURES:
      This patient acquired a traumatically induced syrinx in his upper cervical spinal
      cord after he fell approximately 9 feet and landed on his head, upper back, and
      neck 9 years before presenting for care. He was diagnosed with a spinal cord cyst
      (syrinx), located at approximately C2 through C4 after magnetic resonance
      imaging. In 1995, the patient underwent occipitoatlantal decompression surgery,
      which improved his symptoms for a short time. INTERVENTION AND OUTCOMES: The
      patient was treated using Clinical Biomechanics of Posture protocol. The patient
      was seen 26 times over the course of 3 weeks. His scale for pain severity
      decreased 50% and other subjective complaints decreased. His posture improved
      based upon pretreatment and posttreatment lateral cervical radiographs, showing a
      change from a 10 degrees lordosis with midcervical kyphosis to a 30 degrees
      lordosis. One-year follow-up examination showed stable improvement in the
      cervical lordosis and pain intensity. CONCLUSION: This case represents a change
      in subjective and objective measurements after conservative chiropractic care.
      This case provides an example that structural rehabilitation may have a positive
      effect on symptoms of a patient with syringomyelia.

PMID- 16096047
TI  - The evidence-based hierarchy: is it time for change? A suggested alternative.

PMID- 16096048
TI  - Multidisciplinary rehabilitation practice: an example from the field.

PMID- 16096049
TI  - A revised definition of manipulation.

PMID- 16096050
TI  - Splicing misplaced.
AB  - Newly synthesized transcripts are usually spliced during transcription or
      immediately thereafter. So pre-mRNA splicing has been presumed to occur
      exclusively in the cell nucleus. In this issue of Cell, Denis et al. (2005) now
      report the presence of functional spliceosomes and signal-dependent pre-mRNA
      splicing in the cytoplasm of platelets.

PMID- 16096051
TI  - Nicastrin: gatekeeper of the gamma-secretase complex.
AB  - The gamma-secretase intramembrane protease cleaves many type I membrane proteins
      including amyloid precursor protein and Notch, generating peptide fragments that
      are important signaling components. In this issue of Cell, Shah et al. (2005)
      reveal the function of nicastrin, the largest member of the gamma-secretase
      complex. They show that the nicastrin extracellular domain is essential for
      recognition of substrate by the gamma-secretase.

PMID- 16096052
TI  - Salmonella's sensor for host defense molecules.
AB  - The bacterial pathogen Salmonella typhimurium resides within phagosomes in host
      cells and is able to deflect the host immune response. In this issue of Cell,
      Bader et al. (2005) decipher an elegant mechanism by which the PhoQ sensor kinase
      of Salmonella is switched on by host cationic antimicrobial peptides, leading to
      changes in gene expression that enable Salmonella to combat the host immune
      response.

PMID- 16096053
TI  - Transposons reanimated in mice.
AB  - Transposons have proved valuable in the genetic modification of many organisms
      but not mammals. New work reported by Ding et al. (2005) in this issue of Cell
      and by Collier et al. (2005) and Dupuy et al. (2005) in a recent issue of Nature
      now reveals that insertional mutagenesis in mammalian cells is possible thanks to
      modified derivatives of the piggyBac and Sleeping Beauty DNA transposons.
      However, the slow rate of proliferation of DNA transposons suggests that
      derivatives of the L1 retrotransposon might be more powerful for mutagenesis of
      germline cells. In either case, the future of transposon-driven genetic analyses
      of mice and other mammals looks promising.

PMID- 16096054
TI  - How the T cell receptor sees antigen--a structural view.
AB  - Structures of many of the cell surface receptor-ligand complexes mediating the
      interactions between T cells and target cells have been determined in the past
      ten years. While snapshots of T cell receptors bound to their peptide-MHC ligands
      appear to have defined a general interaction or "docking" solution, many of the
      most fundamental structural questions in antigen recognition lack detailed
      answers and thus pose exciting experimental challenges for the future.

PMID- 16096055
TI  - Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet
      dysfunction in human type 2 diabetes.
AB  - beta cell dysfunction is a central component of the pathogenesis of type 2
      diabetes. Using oligonucleotide microarrays and real-time PCR of pancreatic
      islets isolated from humans with type 2 diabetes versus normal glucose-tolerant
      controls, we identified multiple changes in expression of genes known to be
      important in beta cell function, including major decreases in expression of
      HNF4alpha, insulin receptor, IRS2, Akt2, and several glucose-metabolic-pathway
      genes. There was also a 90% decrease in expression of the transcription factor
      ARNT. Reducing ARNT levels in Min6 cells with small interfering RNA (siRNA)
      resulted in markedly impaired glucose-stimulated insulin release and changes in
      gene expression similar to those in human type 2 islets. Likewise, beta cell
      specific ARNT knockout mice exhibited abnormal glucose tolerance, impaired
      insulin secretion, and changes in islet gene expression that mimicked those in
      human diabetic islets. Together, these data suggest an important role for
      decreased ARNT and altered gene expression in the impaired islet function of
      human type 2 diabetes.

PMID- 16096056
TI  - Allosteric modulation of the RNA polymerase catalytic reaction is an essential
      component of transcription control by rifamycins.
AB  - Rifamycins, the clinically important antibiotics, target bacterial RNA polymerase
      (RNAP). A proposed mechanism in which rifamycins sterically block the extension
      of nascent RNA beyond three nucleotides does not alone explain why certain RNAP
      mutations confer resistance to some but not other rifamycins. Here we show that
      unlike rifampicin and rifapentin, and contradictory to the steric model,
      rifabutin inhibits formation of the first and second phosphodiester bonds. We
      report 2.5 A resolution structures of rifabutin and rifapentin complexed with the
      Thermus thermophilus RNAP holoenzyme. The structures reveal functionally
      important distinct interactions of antibiotics with the initiation sigma factor.
      Strikingly, both complexes lack the catalytic Mg2+ ion observed in the apo
      holoenzyme, whereas an increase in Mg2+ concentration confers resistance to
      rifamycins. We propose that a rifamycin-induced signal is transmitted over
      approximately 19 A to the RNAP active site to slow down catalysis. Based on
      structural predictions, we designed enzyme substitutions that apparently
      interrupt this allosteric signal.

PMID- 16096057
TI  - Inactivation of the SR protein splicing factor ASF/SF2 results in genomic
      instability.
AB  - SR proteins constitute a family of pre-mRNA splicing factors now thought to play
      several roles in mRNA metabolism in metazoan cells. Here we provide evidence that
      a prototypical SR protein, ASF/SF2, is unexpectedly required for maintenance of
      genomic stability. We first show that in vivo depletion of ASF/SF2 results in a
      hypermutation phenotype likely due to DNA rearrangements, reflected in the rapid
      appearance of DNA double-strand breaks and high-molecular-weight DNA fragments.
      Analysis of DNA from ASF/SF2-depleted cells revealed that the nontemplate strand
      of a transcribed gene was single stranded due to formation of an RNA:DNA hybrid,
      R loop structure. Stable overexpression of RNase H suppressed the DNA
      fragmentation and hypermutation phenotypes. Indicative of a direct role, ASF/SF2
      prevented R loop formation in a reconstituted in vitro transcription reaction.
      Our results support a model by which recruitment of ASF/SF2 to nascent
      transcripts by RNA polymerase II prevents formation of mutagenic R loop
      structures.

PMID- 16096059
TI  - Regulation of nuclear proteasome by Rhp6/Ubc2 through ubiquitination and
      destruction of the sensor and anchor Cut8.
AB  - While proteasome is central to the degradation of cellular ubiquitinated
      proteins, the control of its nuclear function is barely understood. Here we show
      that the fission yeast ubiquitin-conjugating Rhp6/Ubc2/Rad6 and ligating enzymes
      Ubr1 are responsible for nuclear enrichment of proteasome through the function of
      Cut8, a nuclear envelope protein. Cut8 is an Rhp6 substrate that physically
      interacts with and tethers proteasome. Nonubiquitinatable K-all-R Cut8 weakly
      interacts with proteasome and fails to enrich nuclear proteasome. Consistently,
      the nuclear enrichment of proteasome also fails in rhp6 and ubr1 null mutants.
      Further, cut8 null and cut8 K-all-R mutants are hypersensitive to DNA damage,
      probably due to the paucity of nuclear proteasome. Thus, Rhp6 enhances the
      retention of nuclear proteasome through regulating Cut8. The short-lived nature
      of Cut8 is crucial for feedback enrichment of the proteasome within the nucleus.
      This is likely to be a conserved mechanism as we describe a Cut8 homolog in
      flies.

PMID- 16096058
TI  - Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate
      platelets.
AB  - Platelets are specialized hemostatic cells that circulate in the blood as
      anucleate cytoplasts. We report that platelets unexpectedly possess a functional
      spliceosome, a complex that processes pre-mRNAs in the nuclei of other cell
      types. Spliceosome components are present in the cytoplasm of human
      megakaryocytes and in proplatelets that extend from megakaryocytes. Primary human
      platelets also contain essential spliceosome factors including small nuclear
      RNAs, splicing proteins, and endogenous pre-mRNAs. In response to integrin
      engagement and surface receptor activation, platelets precisely excise introns
      from interleukin-1beta pre-mRNA, yielding a mature message that is translated
      into protein. Signal-dependent splicing is a novel function of platelets that
      demonstrates remarkable specialization in the regulatory repertoire of this
      anucleate cell. While this mechanism may be unique to platelets, it also suggests
      previously unrecognized diversity regarding the functional roles of the
      spliceosome in eukaryotic cells.

PMID- 16096060
TI  - Cdk1-dependent regulation of the mitotic inhibitor Wee1.
AB  - The Wee1 kinase phosphorylates and inhibits cyclin-dependent kinase 1 (Cdk1),
      thereby delaying entry into mitosis until appropriate conditions have been met.
      An understanding of the mechanisms that regulate Wee1 should provide new insight
      into how cells make the decision to enter mitosis. We report here that Swe1, the
      budding-yeast homolog of Wee1, is directly regulated by Cdk1. Phosphorylation of
      Swe1 by Cdk1 activates Swe1 and is required for formation of a stable Swe1-Cdk1
      complex that maintains Cdk1 in the inhibited state. Dephosphorylation of Cdk1
      leads to further phosphorylation of Swe1 and release of Cdk1. Thus, Cdk1 both
      positively and negatively regulates its own inhibitor. Regulation of the Swe1
      Cdk1 complex is likely to play a critical role in controlling the transition into
      mitosis.

PMID- 16096061
TI  - The Hippo signaling pathway coordinately regulates cell proliferation and
      apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP.
AB  - Coordination between cell proliferation and cell death is essential to maintain
      homeostasis in multicellular organisms. In Drosophila, these two processes are
      regulated by a pathway involving the Ste20-like kinase Hippo (Hpo) and the NDR
      family kinase Warts (Wts; also called Lats). Hpo phosphorylates and activates
      Wts, which in turn, through unknown mechanisms, negatively regulates the
      transcription of cell-cycle and cell-death regulators such as cycE and diap1.
      Here we identify Yorkie (Yki), the Drosophila ortholog of the mammalian
      transcriptional coactivator yes-associated protein (YAP), as a missing link
      between Wts and transcriptional regulation. Yki is required for normal tissue
      growth and diap1 transcription and is phosphorylated and inactivated by Wts.
      Overexpression of yki phenocopies loss-of-function mutations of hpo or wts,
      including elevated transcription of cycE and diap1, increased proliferation,
      defective apoptosis, and tissue overgrowth. Thus, Yki is a critical target of the
      Wts/Lats protein kinase and a potential oncogene.

PMID- 16096062
TI  - Nicastrin functions as a gamma-secretase-substrate receptor.
AB  - gamma-secretase catalyzes the intramembrane cleavage of amyloid precursor protein
      (APP) and Notch after their extracellular domains are shed by site-specific
      proteolysis. Nicastrin is an essential glycoprotein component of the gamma
      secretase complex but has no known function. We now show that the ectodomain of
      nicastrin binds the new amino terminus that is generated upon proteolysis of the
      extracellular APP and Notch domains, thereby recruiting the APP and Notch
      substrates into the gamma-secretase complex. Chemical- or antibody-mediated
      blocking of the free amino terminus, addition of purified nicastrin ectodomain,
      or mutations in the ectodomain markedly reduce the binding and cleavage of
      substrate by gamma-secretase. These results indicate that nicastrin is a receptor
      for the amino-terminal stubs that are generated by ectodomain shedding of type I
      transmembrane proteins. Our data are consistent with a model where nicastrin
      presents these substrates to gamma-secretase and thereby facilitates their
      cleavage via intramembrane proteolysis.

PMID- 16096063
TI  - Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium.
AB  - The first event in light perception is absorption of a photon by an opsin
      pigment, which induces isomerization of its 11-cis-retinaldehyde chromophore.
      Restoration of light sensitivity to the bleached opsin requires chemical
      regeneration of 11-cis-retinaldehyde through an enzymatic pathway called the
      visual cycle. The isomerase, which converts an all-trans-retinyl ester to 11-cis
      retinol, has never been identified. Here, we performed an unbiased cDNA
      expression screen to identify this isomerase. We discovered that the isomerase is
      a previously characterized protein called Rpe65. We confirmed our identification
      of the isomerase by demonstrating catalytic activity in mammalian and insect
      cells that express Rpe65. Mutations in the human RPE65 gene cause a blinding
      disease of infancy called Leber congenital amaurosis. Rpe65 with the Leber
      associated C330Y and Y368H substitutions had no isomerase activity.
      Identification of Rpe65 as the isomerase explains the phenotypes in rpe65-/-
      knockout mice and in humans with Leber congenital amaurosis.

PMID- 16096064
TI  - Recognition of antimicrobial peptides by a bacterial sensor kinase.
AB  - PhoQ is a membrane bound sensor kinase important for the pathogenesis of a number
      of Gram-negative bacterial species. PhoQ and its cognate response regulator PhoP
      constitute a signal-transduction cascade that controls inducible resistance to
      host antimicrobial peptides. We show that enzymatic activity of Salmonella
      typhimurium PhoQ is directly activated by antimicrobial peptides. A highly acidic
      surface of the PhoQ sensor domain participates in both divalent-cation and
      antimicrobial-peptide binding as a first step in signal transduction across the
      bacterial membrane. Identification of PhoQ signaling mutants, binding studies
      with the PhoQ sensor domain, and structural analysis of this domain can be
      incorporated into a model in which antimicrobial peptides displace divalent
      cations from PhoQ metal binding sites to initiate signal transduction. Our
      findings reveal a molecular mechanism by which bacteria sense small innate immune
      molecules to initiate a transcriptional program that promotes bacterial
      virulence.

PMID- 16096065
TI  - Efficient transposition of the piggyBac (PB) transposon in mammalian cells and
      mice.
AB  - Transposable elements have been routinely used for genetic manipulation in lower
      organisms, including generating transgenic animals and insertional mutagenesis.
      In contrast, the usage of transposons in mice and other vertebrate systems is
      still limited due to the lack of an efficient transposition system. We have
      tested the ability of piggyBac (PB), a DNA transposon from the cabbage looper
      moth Trichoplusia ni, to transpose in mammalian systems. We show that PB elements
      carrying multiple genes can efficiently transpose in human and mouse cell lines
      and also in mice. PB permits the expression of the marker genes it carried.
      During germline transposition, PB could excise precisely from original insertion
      sites and transpose into the mouse genome at diverse locations, preferably
      transcription units. These data provide a first and critical step toward a highly
      efficient transposon system for a variety of genetic manipulations including
      transgenesis and insertional mutagenesis in mice and other vertebrates.

PMID- 16096067
TI  - Will psychoanalytic pluralism be an enduring state of our discipline?

PMID- 16096068
TI  - Who is 'who' in dissociation?: A plea for psychodynamics in a time of trauma.
AB  - Contemporary theories of dissociation and trauma for the most part have evolved
      outside of psychoanalysis. Psychoanalytic writings have also been regarded as
      being in opposition to trauma-based notions of human psychopathology. The
      specific psychoanalytic contribution--the emphasis on unconscious conflict and
      meaning--is for the most part excluded from the discourse on dissociation, often
      resulting in a 'mechanic' conceptualisation of trauma. In this paper, based on
      clinical material, the author argues in favour of including conflict, unconscious
      intention and personal meaning in understanding the kind of dissociation we see
      in cases of multiple personality pathology. Textual analysis of letters written
      to the analyst illustrates how events of abuse are defensively elaborated. The
      author demonstrates that patterns of affect regulation and dominant object
      relational strategies can be captured through analysis of the discourse
      structure. She focuses on how an organised character pattern, revealed mainly
      through narrative style and the analyst's countertransference, serves protective
      purposes as well as wish-fulfillment. She argues that dissociation in the form of
      multiple personalities may imply an active, strategic agent.

PMID- 16096069
TI  - Early trauma and narcissism-autism bipolarity.
AB  - The analyst makes a series of considerations taken--a posteriori--from the
      analysis of a small number of patients. These patients have saved themselves from
      an early narcissistic catastrophe by developing precocious mental processes,
      while affective relationships rudimentarily repeat the impact with the original
      trauma. Primitive defences, essentially denial and vertical splitting, dissociate
      the tear in the psyche and structure a 'narcissism-autism bipolarity', revealed
      in aspects of the character which oblige the patient to automatically repeat a
      single matrix of experience. In therapy, it is necessary to construct a 'first
      time of the trauma', by finding and linking threads of the primary relationship
      and strengthening them in the analytic relationship. This reconstruction of the
      background, a screen to project what had originally been rejected, is the
      prerequisite for coming out, in deferred action, from the hold of the
      pathological identifications. The author dedicates particular attention to the
      undifferentiated background, the nature-environment torn by the trauma, and to
      the need to reconstruct this fabric of experience in the analytical relationship,
      as a fundamental element to the recomposition of the dissociated nuclei. In the
      clinical case, the analyst describes in particular how the analyst's words
      encounter an unbridgeable gap, a failure in the capacity for representation when
      opening the autistic nucleus. Through a regression lasting for about a year, a
      patient was able to live the experience of 'primitive agonies' and that of an
      unbearable helplessness and, at the same time, was able to feel how the analyst
      supported her sense of existence. Subsequently, the patient was able to give
      shape, through visual images, to deep states of being and start the process of
      metabolising and symbolising the trauma.

PMID- 16096070
TI  - Affect and the therapeutic action of psychoanalysis.
AB  - In connection with controversial IJP articles by Stern et al. and Fonagy on the
      interpretation of the repressed and the recovery of past memories, the author
      maintains that the affect that is inherent in positive transference is at the
      heart of therapeutic action. Points of view put forward in the controversy (based
      on neurobiological knowledge) are related to Freudian metapsychology, as well as
      to their precursors whose scope was necessarily limited by a lack of access to
      more recent scientific discoveries. The author demonstrates metapsychological
      elements of therapeutic action inherent in the intersubjective relationship,
      especially identification, manifested in introjection and empathy. He describes
      cognitive development as spontaneously blossoming from the affective nucleus, and
      he explains the neuroscientific bases of this step forward. The classic
      (interpretative) psychoanalytic method makes up the cognitive superstructure
      necessary for the organisation of the mind that has sprung from the affective
      substructure. As a primary factor in psychic change, interpretation is limited in
      effectiveness to pathologies arising from the verbal phase, related to explicit
      memories, with no effect in the pre-verbal phase where implicit memories are to
      be found. Interpretation--the method used to the exclusion of all others for a
      century--is only partial; when used in isolation it does not meet the demands of
      modern broad-spectrum psychoanalysis, as the clinical material presented
      illustrates.

PMID- 16096071
TI  - From bastion to enactment: the 'non-dream' in the theatre of analysis.
AB  - In this paper, the author's objective is to discuss models that express what
      occurs in the analytical situation. He demonstrates how early models relating to
      painting and sculpture, to history and archaeology, develop into other models
      that refer to the relationship between two people. He studies in depth the
      Barangers' 'analytical field' with its obstructive bastions as a background to
      understanding what is currently valued as intersubjectivity in psychoanalysis.
      The container-contained model and the phenomenon of 'recruitment' are also
      discussed. The author uses clinical material to demonstrate how these models are
      linked to 'enactment', and a study of this concept provides evidence of the
      importance of the visual image, the dream and 'non-dream', the 'affective
      pictogram', as privileged aspects for the understanding and evolution of thought
      in the analytical process. Its importance leads to a proposal of a model that
      uses the theatre as a metaphor for the analytical process. In this model, analyst
      and patient both participate as characters in the scenes, and simultaneously as
      their co-authors. The analyst should also be responsible for the direction of
      scenes, as well as acting as critic. His task is to prevent obstructive
      conspiracies (the 'non-dream') and find new meanings for the scenes, thus
      allowing the development of new scenes and plots, and the enlarging of the mental
      universe.

PMID- 16096072
TI  - From mimesis to agency: clinical steps in the work of psychic two-ness.
AB  - In this paper, through the study of the clinical process of a girl starting
      treatment at the age of 3 years 10 months, who was thought of as a 'dummy' by her
      family and who came for consultation when the assumed genetic aetiology was
      questioned, the authors build upon Tustin's contributions on the context of
      togetherness and the crisis of two-ness, and upon Eugenio and Renata Gaddini's on
      the precursor object. The mimetic phenomena enacted with an older brother and at
      the kindergarten are found to result from cumulative trauma at her contacting a
      loving but mind-blind mother. After an initial stage of transference autism,
      enactment in the session of the traumatic situation was the ?rst step in
      surmounting her autistic pseudo-stupidity. Mimetic transference dynamics took
      place principally at the level of the gaze, leading to the unfolding of the work
      of two-ness to a differentiation from the analyst as psychic breast, on the road
      to symbol formation and personal agency.

PMID- 16096073
TI  - The many faces of lying.
AB  - In this paper the author explores the psychic functions of lying and draws on
      Glasser's (1979) notions of self-preservative and sadistic violence to identify
      three selfobject configurations. Each of these is associated with specific
      anxieties to which the lie offers an apparent solution. The first configuration
      is sadistic lying. Here the intent is to attack and triumph over the duped other.
      The lie allows the object to be controlled and humiliated. This gratifies the
      self by reversing an earlier humiliation. The second and third configurations are
      both forms of self-preservative lying, where the lie may be best conceived as a
      'symptom of hope' (Winnicott, 1985). In the second configuration, the object is
      felt to be unavailable or inscrutable. The lie may be used to create an
      attractive self that will elicit the object's love, admiration and concern. In
      this way, the lie serves to eliminate doubt about the object's intentions towards
      the self. In the third configuration, the object is felt to be intrusive, and the
      dyadic relationship is overpowering. Here the lie can represent an attempt to
      insert a third into the relationship.

PMID- 16096074
TI  - Perverse relationships: the perspective of the perpetrator.
AB  - The author examines the theme of perverse relationships within the couple,
      focusing on the question of men's maltreatment of their female partners,
      particularly in the psychological sense. Various aspects of the perpetrator's
      personality and relational style are described. The author takes as her starting
      point and discusses in depth the concepts of 'narcissistic perversion' (Racamier,
      1992) and 'relational perversion' (Pandolfi, 1999), considered useful for
      understanding and identifying this type of pathology. She postulates that
      maltreating behaviour, in fact, originates from the encounter of particularly non
      empathic relational styles which are typical of certain personalities (mainly,
      but not exclusively, of the narcissistic disorder) with 'perversity', that is,
      perversion, understood as a character trait. The author makes a distinction
      between 'relational perversion' and 'sado-masochistic relationship', and presents
      a clinical picture deriving from the analysis of a man who maltreats his
      companion, in order to shed light on the above-mentioned aspects, touching on
      some problems arising in the analysis of such patients. In conclusion, she
      considers some aspects of the experience of victims of maltreatment.

PMID- 16096075
TI  - Why perversion?: 'False love' and the perverse pact.
AB  - In this paper, the author works with the awareness that perversion is a socially,
      historically and theologically loaded term, at the same time as it may be the
      latest frontier in psychoanalysis, both clinically, and in relation to
      contemporary art and culture which emphasize the perverse. Positioning itself
      against tendencies to deny the existence of a category of 'perversion' or,
      inversely, to abuse it for the power that accrues from the act of diagnosing, she
      also points to other liabilities in the history of the treatment of this term,
      such as the narrowing down of perversion to the exclusively sexual domain, or,
      alternatively, the overextension of it to polymorphously erotic practices that
      enhance sexual excitement. The paradoxes of perversion and the difficulties of
      distinguishing the perverse from the non-perverse are addressed. The case is also
      made that, in order to understand perversion, one must unlink it from the narrow
      notion of sexual practice and see what is involved on a deeper level--an approach
      initiated when psychoanalysis turned to perversion as a defense against psychotic
      anxieties, and began considering the necessary place of perversion in the
      transference--countertransference. Two features common to both sexual and non
      sexual perverse relations are the seductive and bribing aspects of perversion,
      and its means-ends reversal. Perversion is a haven for the disguising of hatred
      and suspicion as excitement and (false) love. Displaced child and beating father,
      entitled child and seductive mother, are both prototypes of psychoanalytic
      reflection on parents who excite, deceive and corrupt their children and
      establish perverse pacts with them. The notion of the perverse pact is
      foregrounded in Alice's analysis, where first the resurrection and then the
      dismantling of such a pact were effected through various analytic means.

PMID- 16096076
TI  - Metaphor and the violent.
AB  - During the treatment of violent individuals who were, incidentally, highly
      verbal, the authors noticed that physical assaults were often preceded by the
      perpetrator' s use of metaphors. It was observed that the linguistic metaphors
      failed to function as ordinary 'as if' devices and became 'concretised'. When
      this occurred, the perpetrators resorted to a physical attack. In this paper, the
      authors argue that the capacity to interconnect (which is considered to be the
      essence of psychic work) is dependent upon what can be conceptualised as a
      primary mental 'frame' or 'warp'. Distortion of the warp will, in turn, weaken
      the 'weaving', or interconnecting function of the ego, which is considered
      analogous to the interconnecting in linguistic metaphors. Clinical material from
      the treatment of three violent men (two in psychotherapy and one in analysis) is
      used to illustrate the hypothesis that the concretised use of metaphor represents
      a restitutive, but failed attempt to maintain a psychic coherence in the face of
      an imminent breakdown.

PMID- 16096077
TI  - Experiences in K and -K.
AB  - In this paper the author explores and expands Bion's concepts of K and -K and
      delineates the nature of the relationship between the two. While Bion views envy
      as a principal motivating force for -K, his conception of -K goes considerably
      beyond this. The author explores manifestations of -K not driven by envy and,
      consequently, not necessarily pathological or pathogenic. -K is viewed by the
      author as a psychological process, which may serve many functions, including the
      communication of the patient's fear that knowing will bring on psychological
      catastrophe. -K, under circumstances that he describes, may serve to protect the
      individual's sense of continuity of being. The need to know the truth (K) may be
      at odds with the need to survive psychically, for example, when a person fears
      that the truth will kill him, or those he loves and depends upon. This idea is
      explored in two ways: first, by means of a discussion of the Oedipus myth in
      which Oedipus attempts to evade knowing for fear of recognizing that a prophesied
      catastrophe has already occurred; and, second, by means of a clinical exploration
      of the conflict between the need to know and the need to survive. The author
      discusses his analytic work with a severely disturbed patient for whom not
      knowing was felt to be essential to her psychic survival. Her need not to know
      reached a point where she psychically obliterated the analyst through the use of
      negative hallucination.

PMID- 16096078
TI  - Are psychodynamic and psychoanalytic therapies effective?: A review of empirical
      data.
AB  - There is a need for empirical outcome research in psychodynamic and
      psychoanalytic therapy. However, both the approach of empirically supported
      therapies (EST) and the procedures of evidence-based medicine (EBM) have severe
      limitations making randomised controlled trials (RCTs) an absolute standard.
      After a critical discussion of this approach, the author reviews the empirical
      evidence for the efficacy of psychodynamic psychotherapy in specific psychiatric
      disorders. The review aims to identify for which psychiatric disorders RCTs of
      specific models of psychodynamic psychotherapy are available and for which they
      are lacking, thus providing a basis for planning further research. In addition,
      results of process research of psychodynamic psychotherapy are presented. As the
      methodology of RCTs is not appropriate for psychoanalytic therapy, effectiveness
      studies of psychoanalytic therapy are reviewed as well. Studies of psychodynamic
      psychotherapy published between 1960 and 2004 were identified by a computerised
      search using Medline, PsycINFO and Current Contents. In addition, textbooks and
      journal articles were used. Twenty-two RCTs were identified of which 64% had not
      been included in the 1998 report by Chambless and Hollon. According to the
      results, for the following psychiatric disorders at least one RCT providing
      evidence for the efficacy of psychodynamic psychotherapy was identified:
      depressive disorders (4 RCTs), anxiety disorders (1 RCT), post-traumatic stress
      disorder (1 RCT), somatoform disorder (4 RCTs), bulimia nervosa (3 RCTs),
      anorexia nervosa (2 RCTs), borderline personality disorder (2 RCTs), Cluster C
      personality disorder (1 RCT), and substance-related disorders (4 RCTs). According
      to results of process research, outcome in psychodynamic psychotherapy is related
      to the competent delivery of therapeutic techniques and to the development of a
      therapeutic alliance. With regard to psychoanalytic therapy, controlled quasi
      experimental effectiveness studies provide evidence that psychoanalytic therapy
      is (1) more effective than no treatment or treatment as usual, and (2) more
      effective than shorter forms of psychodynamic therapy. Conclusions are drawn for
      future research.

PMID- 16096079
TI  - Melanie Klein in Buenos Aires: beginnings and developments.
AB  - In the first decades of the 20th century, Freud was known and quoted in Latin
      America by an elite of enlightened minds. In the 1940s a convergence took place
      in Buenos Aires of European exiles with local pioneers, and thus the Argentine
      Psychoanalytical Association was founded in 1942. Since then psychoanalysis has
      grown steadily and has spread into hospitals and universities, influencing
      culture at large. The socioeconomic situation of that time permitted this
      phenomenon to develop, to the astonishment of observers. In this paper the
      authors study the strong influence of Kleinian thought during the first 30 years
      of this development. The original works of local thinkers constitute the
      intellectual capital that sustains the idea of an 'Argentine psychoanalytic
      school'. During the 1970s, both society and psychoanalysis endured deep and
      complex changes. Lacan's teachings gained support and Klein's influence began to
      decline. At present the Buenos Aires Kleinians keep working, while their
      relationship with Lacanians and other schools is calmer. Respectful discussions
      became thus possible, oriented to strictly scientific differences.

PMID- 16096080
TI  - On: the cause is worse: remeeting Jocasta.

PMID- 16096085
TI  - Spiders that decorate their webs at higher frequency intercept more prey and grow
      faster.
AB  - Many orb-weaving spiders decorate their webs with extra, bright white,
      ultraviolet light reflecting silk. Previous studies suggest that these
      decorations increase a spider's foraging efficiency by improving web
      attractiveness, which is known as the prey-attraction hypothesis. One assumption
      of this hypothesis is that individuals which decorate their webs at a higher
      frequency are expected to have a higher growth rate. Using a decoration-building
      orb-weaving spider, Argiope versicolor, I show a strong positive relationship
      between the growth rate in terms of weight gain and the frequency of decoration
      building, as well as the rate of insect interception. This is the first study to
      reveal a fitness consequence of decorating behaviour in spiders.

PMID- 16096084
TI  - Photoreceptor spectral sensitivities in terrestrial animals: adaptations for
      luminance and colour vision.
AB  - This review outlines how eyes of terrestrial vertebrates and insects meet the
      competing requirements of coding both spatial and spectral information. There is
      no unique solution to this problem. Thus, mammals and honeybees use their long
      wavelength receptors for both achromatic (luminance) and colour vision, whereas
      flies and birds probably use separate sets of photoreceptors for the two
      purposes. In particular, we look at spectral tuning and diversification among
      'long-wavelength' receptors (sensitivity maxima at greater than 500 nm), which
      play a primary role in luminance vision. Data on spectral sensitivities and
      phylogeny of visual photopigments can be incorporated into theoretical models to
      suggest how eyes are adapted to coding natural stimuli. Models indicate, for
      example, that animal colour vision--involving five or fewer broadly tuned
      receptors--is well matched to most natural spectra. We can also predict that the
      particular objects of interest and signal-to-noise ratios will affect the optimal
      eye design. Nonetheless, it remains difficult to account for the adaptive
      significance of features such as co-expression of photopigments in single
      receptors, variation in spectral sensitivities of mammalian L-cone pigments and
      the diversification of long-wavelength receptors that has occurred in several
      terrestrial lineages.

PMID- 16096086
TI  - An analytical model assessing the potential threat to natural habitats from
      insect resistance transgenes.
AB  - We examine the role of ecological interactions on effective gene flow from
      genetically manipulated plants to their wild relatives. We do so by constructing
      and applying to oilseed rape (OSR) an analytical model for interaction between
      plants with and without an insect resistance (IR) allele in natural communities,
      incorporating documented levels of herbivore variability. We find that with
      reasonable values of advantage to the IR allele, little concomitant disadvantage
      (physiological costs of the allele) restricts it to low proportions of the
      natural population for large numbers of generations. We conclude that OSR IR
      transgenes are unlikely to pose an immediate threat to natural communities. Our
      model identifies those factors best able to regulate particular transgenes at the
      population level, the most effective being impaired viability of seeds in the
      period between production and the following growing season, although other
      possibilities exist. Because solutions rely on ratios, limiting values of
      regulating factors are testable under controlled conditions, minimizing risk of
      release into the environment and offering significant advancement on existing
      testing programmes. Our model addresses folivory but is easily modified for
      herbivory damaging the seed or directly affecting seed production by infested
      plants, or for pathogens altering seed survival in the seedbank.

PMID- 16096087
TI  - Terror birds on the run: a mechanical model to estimate its maximum running
      speed.
AB  - 'Terror bird' is a common name for the family Phorusrhacidae. These large
      terrestrial birds were probably the dominant carnivores on the South American
      continent from the Middle Palaeocene to the Pliocene-Pleistocene limit. Here we
      use a mechanical model based on tibiotarsal strength to estimate maximum running
      speeds of three species of terror birds: Mesembriornis milneedwardsi, Patagornis
      marshi and a specimen of Phorusrhacinae gen. The model is proved on three living
      large terrestrial bird species. On the basis of the tibiotarsal strength we
      propose that Mesembriornis could have used its legs to break long bones and
      access their marrow.

PMID- 16096088
TI  - Maternal influences on brood sex ratios: an experimental study in tree swallows.
AB  - When the reproductive value of sons and daughters differ, parents are expected to
      adjust the sex ratio of their offspring to produce more of the sex that provides
      greater fitness returns. The body condition of females or environmental factors,
      such as food abundance and mate quality, may influence these expected fitness
      returns. In a previous study of tree swallows (Tachycineta bicolor), we found
      that females produced more sons in their broods when they were in better body
      condition (mass corrected for size). We tested this relationship by
      experimentally clipping some flight feathers to reduce female body condition. As
      predicted, we found that females with clipped feathers had a lower proportion of
      sons in their broods and poorer body condition. However, female body condition
      alone was not a significant predictor of brood sex ratio in our experiment. We
      suggest that brood sex ratio is causally related to some other factor that
      covaries with body condition, most likely the foraging ability of females. The
      hypothesis that brood sex ratios are influenced by individual differences in
      female foraging ability is supported by a high repeatability of brood sex ratio
      for individual females. Thus, maternal effects may have a strong influence on the
      sex ratios of offspring.

PMID- 16096089
TI  - Do female Drosophila melanogaster adaptively bias offspring sex ratios in
      relation to the age of their mate?
AB  - Modification of offspring sex ratios in response to parental quality is predicted
      when the long-term fitness returns of sons and daughters differ. One factor that
      may influence a mother's sex allocation decision is the quality (or
      attractiveness) of her mate. We investigated whether the sex ratios of offspring
      produced by female Drosophila melanogaster are biased with respect to the age of
      the males to which they are mated, and whether there is an adaptive basis for
      this phenomenon. We found that females mated to old males (13 d post-eclosion)
      initially produced a greater proportion of daughters than did females mated to
      young males (1 d post-eclosion). This pattern does not appear to be due to a
      systematic difference in the numbers or mortality of the X- and Y-bearing sperm
      originating from old and young fathers, as the overall sex ratios of all
      offspring produced from a single copulation did not differ between broods
      fathered by the two types of males. The sons of older males fared worse in
      competitive mating assays than did the sons of younger males, while daughters of
      old and young males were of comparable fitness. These results suggest that there
      is an adaptive basis for the observed sex ratio modification.

PMID- 16096090
TI  - Experimental manipulation of queen number affects colony sex ratio investment in
      the highly polygynous ant Formica exsecta.
AB  - In polygynous (multiple queens per nest) ants, queen dispersal is often limited
      with young queens being recruited within the parental colony. This mode of
      dispersal leads to local resource competition between nestmate queens and is
      frequently associated with extremely male-biased sex ratios at the population
      level. The queen-replenishment hypothesis has been recently proposed to explain
      colony sex ratio investment under such conditions. It predicts that colonies
      containing many queens (subject to high local resource competition) should only
      produce males, whereas colonies hosting few queens (reduced or no local resource
      competition) should produce new queens in addition to males. We experimentally
      tested this hypothesis in the ant Formica exsecta by manipulating queen number
      over three consecutive years in 120 colonies of a highly polygynous population.
      Queens were transferred from 40 colonies into another 40 colonies while queen
      number was not manipulated in 40 control colonies. Genetic analyses of worker
      offspring revealed that our treatment significantly changed the number of
      reproductive queens. The sex ratio of colonies was significantly different
      between treatments in the third breeding season following the experiment
      initiation. We found that, as predicted by the queen-replenishment hypothesis,
      queen removal resulted in a significant increase in the proportion of colonies
      that produced new queens. These results provide the first experimental evidence
      for the queen-replenishment hypothesis, which might account for sex ratio
      specialization in many highly polygynous ant species.

PMID- 16096091
TI  - Sex inheritance in gynodioecious species: a polygenic view.
AB  - Gynodioecy is defined as the coexistence of two different sexual morphs in a
      population: females and hermaphrodites. This breeding system is found among many
      different families of angiosperms and is usually under nucleo-cytoplasmic
      inheritance, with maternally inherited genes causing male sterility and nuclear
      factors restoring male fertility. Numerous theoretical models have investigated
      the conditions for the stable coexistence of females and hermaphrodites. To date,
      all models rest on the assumption that restoration of a given male sterile
      genotype is controlled by a single Mendelian factor. Here, we review data bearing
      on the genetic determinism of sex inheritance in three gynodiecious plant
      species. We suggest that restoration of male fertility is probably best viewed as
      a quantitative trait controlled by many loci. We develop a threshold model that
      accommodates an underlying polygenic trait, which is resolved at the phenotypic
      level in discrete sexual morphs. We use this model to reanalyse data in Thymus
      vulgaris, Silene vulgaris and Plantago coronopus. A simple Mendelian inheritance
      of sex determinism is unlikely in all three species. We discuss how our model can
      shed additional light on the genetics of restoration and point towards future
      efforts in the modelling of gynodioecy.

PMID- 16096092
TI  - Resistance is costly: trade-offs between immunity, fecundity and survival in the
      pea aphid.
AB  - Parasitoids are among the most important natural enemies of insects in many
      environments. Acyrthosiphon pisum, the pea aphid, is a common pest of the
      leguminous crops in temperate regions. Pea aphids are frequently attacked by a
      range of endoparasitic wasps, including the common aphidiine, Aphidius ervi.
      Immunity to parasitoid attack is thought to involve secondary symbiotic bacteria,
      the presence of which is associated with the death of the parasitoid egg. It has
      been suggested that there is a fecundity cost of resistance, as individuals
      carrying the secondary symbionts associated with parasitoid resistance have fewer
      offspring. Supporting this hypothesis, we find a positive relationship between
      fecundity and susceptibility to parasitoid attack. There is also a negative
      relationship between fecundity and off-plant survival time (which positively
      correlates with resistance to parasitoid attack). Taken together, these results
      suggest that the aphids can either invest in defence (parasitoid resistance,
      increased off-plant survival time) or reproduction, and speculate that this may
      be mediated by changes in the aphids' endosymbiont fauna. Furthermore, there is a
      positive relationship between aphid size and resistance, suggesting that
      successful resistance to parasitoid attack may involve physical, as well as
      physiological, defences.

PMID- 16096093
TI  - An empirical test of Lanchester's square law: mortality during battles of the
      fire ant Solenopsis invicta.
AB  - Lanchester's models of attrition describe casualty rates during battles between
      groups as functions of the numbers of individuals and their fighting abilities.
      Originally developed to describe human warfare, Lanchester's square law has been
      hypothesized to apply broadly to social animals as well, with important
      consequences for their aggressive behaviour and social structure. According to
      the square law, the fighting ability of a group is proportional to the square of
      the number of individuals, but rises only linearly with fighting ability of
      individuals within the group. By analyzing mortality rates of fire ants
      (Solenopsis invicta) fighting in different numerical ratios, we provide the first
      quantitative test of Lanchester's model for a non-human animal. Casualty rates of
      fire ants were not consistent with the square law; instead, group fighting
      ability was an approximately linear function of group size. This implies that the
      relative numbers of casualties incurred by two fighting groups are not strongly
      affected by relative group sizes and that battles do not disproportionately
      favour group size over individual prowess.

PMID- 16096094
TI  - Metapopulations in multifractal landscapes: on the role of spatial aggregation.
AB  - The use of fractals in ecology is currently pervasive over many areas. However,
      very few studies have linked fractal properties of landscapes to generating
      ecological mechanisms and dynamics. In this study I show that lacunarity (a
      measure of the landscape texture) is a well suited ecologically scaled landscape
      index that can be explicitly incorporated in metapopulation models such as the
      classical Levins equation. I show that the average lacunarity of an aggregated
      landscape is linearly correlated to the habitat that a species with local spatial
      processed information may perceive. Lacunarity is a computationally feasible
      index to measure, and is related to the metapopulation capacity of landscapes. A
      general approach to multifractal landscapes has been conceived, and some
      analytical results for self-similar landscapes are outlined, including the
      specific effect of landscape heterogeneity, decoupled from that of contagion by
      dispersal. Spatially explicit simulations show agreement with the semi-implicit
      method presented.

PMID- 16096095
TI  - Population effects of increased climate variation.
AB  - Global circulation models predict and numerous observations confirm that
      anthropogenic climate change has altered high-frequency climate variability.
      However, it is not yet well understood how changing patterns of environmental
      variation will affect wildlife population dynamics and other ecological
      processes. Theory predicts that a population's long-run growth rate is diminished
      and the chance of population extinction is increased as environmental variation
      increases. This results from the fact that population growth is a multiplicative
      process and that long-run population growth rate is the geometric mean of growth
      rates over time, which is always less than the arithmetic mean. However, when
      population growth rates for unstructured populations are related nonlinearly to
      environmental drivers, increasing environmental variation can increase a
      population's long-run growth rate. This suggests that patterns of environmental
      variation associated with different aspects of climate change may affect
      population dynamics in different ways. Specifically, increasing variation in
      rainfall might result in diminished long-run growth rates for many animal species
      while increasing variation in temperature might result in increased long-run
      growth rates. While the effect of rainfall is theoretically well understood and
      supported by data, the hypothesized effect of temperature is not. Here, I analyse
      two datasets to study the effect of fluctuating temperatures on growth rates of
      zooplankton. Results are consistent with the prediction that fluctuating
      temperatures should increase long-run growth rates and the frequency of extreme
      demographic events.

PMID- 16096096
TI  - Trans-oceanic and endemic origins of the small minnow mayflies (Ephemeroptera,
      Baetidae) of Madagascar.
AB  - We investigated the relative importance of dispersal and vicariance in forming
      the Madagascar insect fauna, sequencing approximately 2300bp from three rRNA gene
      regions to investigate the phylogeny of Afrotropical small minnow mayflies
      (Ephemeroptera: Baetidae). Six lineages contained trans-oceanic sister taxa, and
      variation in genetic divergence between sister taxa revealed relationships that
      range from very recent dispersal to ancient vicariance. Dispersal was most recent
      and frequent in species that spend the larval stage in standing water, adding to
      evidence that these evolutionarily unstable habitats may select for ecological
      traits that increase dispersal in insects. Ancestral state likelihood analysis
      suggested at least one Afrotropical lineage had its origin in Madagascar,
      demonstrating that unidirectional dispersal from a continental source may be too
      simplistic. We conclude that the Malagasy mayfly fauna should be considered in a
      biogeographical context that extends beyond Madagascar itself, encompassing trans
      oceanic dispersal within multiple lineages.

PMID- 16096097
TI  - Microsatellite diversity suggests different histories for Mediterranean and
      Northern European cattle populations.
AB  - Based on archaeological evidence, the spread of agropastoralism across Europe
      followed two main paths: the Danubian route, along which Neolithic farmers
      expanded north across the central European plains; and the Mediterranean route,
      where migration occurred along the coast of the Mediterranean sea. Here we
      examine 20 cattle breeds from the continent and assess the genetic diversity
      levels and relationships among the breeds using 19 microsatellite markers.
      Additionally, we show evidence that concords with two distinct cattle migrations
      from the Near East, and also demonstrate that Mediterranean cattle breeds may
      have had more recent input from both the Near East and Africa.

PMID- 16096098
TI  - Leptin regulates energetic tradeoffs between body fat and humoural immunity.
AB  - Mounting an immune response requires a relatively substantial investment of
      energy and marked reductions in energy availability can suppress immune function
      and presumably increase disease susceptibility. We have previously demonstrated
      that a moderate reduction in energy stores via partial surgical lipectomy (LIPx)
      impairs humoural immunity of Siberian hamsters (Phodopus sungorus). Here we
      tested the hypothesis that LIPx-induced decreases in immunity are mediated by
      changes in the adipose tissue hormone leptin. Hamsters received bilateral
      surgical removal of inguinal white adipose tissue (IWATx) or sham surgeries
      (Sham). Half the animals in each group received osmotic minipumps containing
      murine leptin (0.5mulh-1 for 10 days) whereas the remaining animals received
      minipumps containing vehicle alone; all animals were subsequently challenged with
      the novel antigen keyhole limpet haemocyanin (KLH). In general, serum leptin and
      anti-KLH antibodies were significantly correlated with one another with higher
      levels generally indicating enhanced immunity. In addition, IWATx hamsters had
      significantly lower serum anti-KLH IgG compared with sham animals. Exogenous
      leptin, however, attenuated LIPx-induced immune suppression but did not affect
      humoural immunity in sham animals. These results suggest that reductions in
      energy availability lead to impairments in humoural immunity and that leptin can
      serve as a neuroendocrine signal between body fat and immunity regulating
      humoural immune responses.

PMID- 16096099
TI  - The role of mutation accumulation in HIV progression.
AB  - The onset of AIDS is characterized by the collapse of the immune system after a
      prolonged asymptomatic period. The mechanistic basis of this disease progression
      has remained obscure, hindering the development of effective therapies. Here I
      present a mechanism that underlies the deterioration of the immune system during
      HIV infection. The elevated turnover of lymphocytes throughout the asymptomatic
      period is postulated to result in the accumulation of deleterious mutations,
      which impairs immunological function, replicative ability and viability of
      lymphocytes. This mutational meltdown is proposed to occur throughout the
      hierarchy of lymphocyte progenitors, resulting in the deterioration of lymphocyte
      regeneration and an ensuing rise in viral loads. A mathematical model is used to
      illustrate this mechanism of progressive immunological deterioration. Mutation
      accumulation may explain not only the decline in CD4+T cells, but also the
      functional deterioration of CD4+T cells, CD8+T cells and B cells, and the
      exhaustion of lymphocyte regeneration.

PMID- 16096100
TI  - Language and imagery: effects of language modality.
AB  - Across spoken languages, properties of wordforms (e.g. the sounds in the word
      hammer) do not generally evoke mental images associated to meanings. However,
      across signed languages, many signforms readily evoke mental images (e.g. the
      sign HAMMER resembles the motion involved in hammering). Here we assess the
      relationship between language and imagery, comparing the performance of English
      speakers and British sign language (BSL) signers in meaning similarity judgement
      tasks. In experiment 1, we found that BSL signers used these imagistic properties
      in making meaning similarity judgements, in contrast with English speakers. In
      experiment 2, we found that English speakers behaved more like BSL signers when
      asked to develop mental images for the words before performing the same task.
      These findings show that language differences can bias users to attend more to
      those aspects of the world encoded in their language than to those that are not;
      and that language modality (spoken versus signed) can affect the degree to which
      imagery is involved in language.

PMID- 16096101
TI  - Introduction: genetic variation and human health.

PMID- 16096102
TI  - Genomic medicine: genetic variation and its impact on the future of health care.
AB  - Advances in genome technology and other fruits of the Human Genome Project are
      playing a growing role in the delivery of health care. With the development of
      new technologies and opportunities for large-scale analysis of the genome,
      transcriptome, proteome and metabolome, the genome sciences are poised to have a
      profound impact on clinical medicine. Cancer prognostics will be among the first
      major test cases for a genomic medicine paradigm, given that all cancer is caused
      by genomic instability, and microarrays allow assessment of patients' entire
      expressed genomes. Analysis of breast cancer patients' expression patterns can
      already be highly correlated with recurrence risks. By integrating clinical data
      with gene expression profiles, imaging, metabolomic profiles and proteomic data,
      the prospect for developing truly individualized care becomes ever more real.
      Notwithstanding these promises, daunting challenges remain for genomic medicine.
      Success will require planning robust prospective trials, analysing health care
      economic and outcome data, assuaging insurance and privacy concerns, developing
      health delivery models that are commercially viable and scaling up to meet the
      needs of the whole population.

PMID- 16096103
TI  - Mapping and identifying genes for asthma and psoriasis.
AB  - Susceptibility genes for complex diseases are characterized by reduced
      penetrance, caused by the influence of other genes, the environment or stochastic
      events. Recently, positional cloning efforts have yielded several candidate
      susceptibility genes in different complex disorders such as Crohn's disease and
      asthma. Within a genetic locus, however, the identification of the effector gene
      may pose further challenges and require functional studies. I review two examples
      of such challenges: the cloning of GPR154 (GPRA) and AAA1 on chromosome 7p14 at a
      susceptibility locus for atopy and asthma, and the study of HLA-Cw6, CCHCR1 (HCR)
      and CDSN on chromosome 6p21 at PSORS1, the major susceptibility locus for
      psoriasis. The susceptibility locus for atopy and asthma contains two genes and
      only one of them is protein coding. We studied its isoform-specific expression in
      bronchial biopsies and in a mouse model of ovalbumin-induced inflammation of
      bronchial epithelia. In the PSORS1 locus, strong linkage disequilibrium between
      genes has made it difficult to distinguish the effects of the three nearby genes.
      We engineered transgenic mice with either a HCR non-risk allele or the HCR*WWCC
      risk allele controlled by the cytokeratin-14 promoter. The results suggested that
      the overexpression of HCR in mouse skin was insufficient to induce a psoriasiform
      phenotype, but it appeared to induce allele-specific gene expression changes that
      were similar to those observed in psoriatic skin.

PMID- 16096105
TI  - The genetics of human drug response.
AB  - The genetics of variable drug response appears to be a more tractable complex
      trait than common disease predisposition. This has implications for prioritizing
      research and for experimental design, and in particular argues for extensive use
      of candidate gene based approaches in pharmacogenetic association studies.
      Eventually, when whole genome scanning becomes feasible, it may be appropriate to
      consider weighting schemes that assign higher prior probabilities of variants in
      genes related to the mode of action of metabolism of medicines.

PMID- 16096104
TI  - Pharmacogenetics of drug-metabolizing enzymes: implications for a safer and more
      effective drug therapy.
AB  - The majority of phase I- and phase II-dependent drug metabolism is carried out by
      polymorphic enzymes which can cause abolished, quantitatively or qualitatively
      decreased or enhanced drug metabolism. Several examples exist where subjects
      carrying certain alleles do not benefit from drug therapy due to ultrarapid
      metabolism caused by multiple genes or by induction of gene expression or,
      alternatively, suffer from adverse effects of the drug treatment due to the
      presence of defective alleles. It is likely that future predictive genotyping for
      such enzymes might benefit 15-25% of drug treatments, and thereby allow
      prevention of adverse drug reactions and causalities, and thus improve the health
      of a significant fraction of the patients. However, it will take time before this
      will be a reality within the clinic. We describe some important aspects in the
      field with emphasis on cytochrome P450 and discuss also polymorphic aspects of
      foetal expression of CYP3A5 and CYP3A7.

PMID- 16096106
TI  - Population genetic approaches to neurological disease: Parkinson's disease as an
      example.
AB  - Parkinson's disease (PD) is a common, progressive, incurable disabling condition.
      The cause is unknown but over the past few years tremendous progress in our
      understanding of the genetic bases of this condition has been made. To date, this
      has almost exclusively come from the study of relatively rare Mendelian forms of
      the disease and there are no currently, widely accepted common variants known to
      increase susceptibility. The role that the "Mendelian" genes play in common
      sporadic forms of PD is unknown. Moreover, most studies in PD can really be
      described as candidate polymorphism studies rather than true and complete
      assessments of the genes themselves. We provide a model of how one might tackle
      some of these issues using Parkinson's disease as an illustration. One of the
      emerging hypotheses of gene environment interaction in Parkinson's disease is
      based on drug metabolizing (or xenobiotic) enzymes and their interaction with
      putative environmental toxins. This motivated us to describe a tagging approach
      for an extensive but not exhaustive list of 55 drug metabolizing enzyme genes. We
      use these data to illustrate the power, and some of the limitations of a
      haplotype tagging approach. We show that haplotype tagging is extremely efficient
      and works well with only a modest increase in effort through different
      populations. The tagging approach works much less well if the minor allele
      frequency is below 5%. However, it will now be possible using these tags to
      evaluate these genes comprehensively in PD and other neurodegenerative
      conditions.

PMID- 16096107
TI  - Pharmacogenetics in drug development.
AB  - Over the last two decades, identification of polymorphisms that influence human
      diseases has begun to have an impact on the provision of medical care. The
      promise of genetics lies in its ability to provide insights into an individual's
      susceptibility to disease, the likely nature of the disease and the most
      appropriate therapy. For much of its history, pharmacogenetics (PGx-the use of
      genetic information to impact drug choice) has been limited to comparatively
      simple phenotypes such as plasma drug levels. Progress in genetics technologies
      has broadened the scope of PGx efficacy and safety studies that can be
      implemented, impacting on a broad spectrum of drug discovery and development
      activities. Recent PGx data show the ability of this approach to generate
      information that can be applied to dose selection, efficacy determination and
      safety issues. This in turn will lead to significant opportunities to affect both
      the approach to clinical development and the probability of success--the latter
      being an important aspect for pharmaceutical companies and for the patients who
      will benefit from these new medicines.

PMID- 16096108
TI  - Prospects and pitfalls in whole genome association studies.
AB  - Recent large-scale studies of common genetic variation throughout the human
      genome are making it feasible to conduct whole genome studies of genotype
      phenotype associations. Such studies have the potential to uncover novel
      contributors to common complex traits and thus lead to insights into the
      aetiology of multifactorial phenotypes. Despite this promise, it is important to
      recognize that the availability of genetic markers and the ability to assay them
      at realistic cost does not guarantee success of this approach. There are a number
      of practical issues that require close attention, some forms of allelic
      architecture are not readily amenable to the association approach with even the
      most rigorous design, and doubtless new hurdles will emerge as the studies begin.
      Here we discuss the promise and current challenges of the whole genome approach,
      and raise some issues to consider in interpreting the results of the first whole
      genome studies.

PMID- 16096109
TI  - Recombination hotspots as a point process.
AB  - The variation of the recombination rate along chromosomal DNA is one of the
      important determinants of the patterns of linkage disequilibrium. A number of
      inferential methods have been developed which estimate the recombination rate and
      its variation from population genetic data. The majority of these methods are
      based on modelling the genealogical process underlying a sample of DNA sequences
      and thus explicitly include a model of the demographic process. Here we propose a
      different inferential procedure based on a previously introduced framework where
      recombination is modelled as a point process along a DNA sequence. The approach
      infers regions containing putative hotspots based on the inferred minimum number
      of recombination events; it thus depends only indirectly on the underlying
      population demography. A Poisson point process model with local rates is then
      used to infer patterns of recombination rate estimation in a fully Bayesian
      framework. We illustrate this new approach by applying it to several population
      genetic datasets, including a region with an experimentally confirmed
      recombination hotspot.

PMID- 16096110
TI  - Will admixture mapping work to find disease genes?
AB  - Admixture mapping is the first experimentally practical method for carrying out a
      whole-genome association scan, and is thus a promising method for detecting risk
      factors for common disease. The goal of the community should now be to
      aggressively test whether the method is useful in practice for localizing disease
      genes, by carrying out at least three high-powered studies. We also propose a
      stringent criteria we believe the community should adopt before declaring a
      statistically significant admixture association to disease.

PMID- 16096111
TI  - Integrating epidemiology and genetic association: the challenge of gene
      environment interaction.
AB  - Recent advances in human genomics have made it possible to better understand the
      genetic basis of disease. In addition, genetic association studies can also
      elucidate the mechanisms by which "non-genetic" exogenous and endogenous
      exposures influence the risk of disease. This is true both of studies that assess
      the marginal effect of a single gene and studies that look at the joint effect of
      genes and environmental exposures. For example, gene variants that are known to
      alter enzyme function or level can serve as surrogates for long-term biomarker
      levels that are impractical or impossible to measure on many subjects. Evidence
      that genetic variants modify the effect of an established risk factor may help
      specify the risk factor's biologically active components. We illustrate these
      ideas with several examples and discuss design and analysis challenges,
      particularly for studies of gene-environment interaction. We argue that to
      increase the power to detect interaction effects and limit the number of false
      positive results, large sample sizes will be needed, which are currently only
      available through planned collaborative efforts. Such collaborations also ensure
      a common approach to measuring variation at a genetic locus, avoiding a problem
      that has led to difficulties when comparing results from genetic association
      studies.

PMID- 16096113
TI  - Editor's introduction: the global epidemiology of HIV and AIDS.

PMID- 16096114
TI  - HIV/AIDS in the Caribbean Basin.
AB  - After Sub-Saharan Africa, the Caribbean Basin has the second highest rate of
      HIV/AIDS in the world. The number of HIV cases in the region is likely to
      increase significantly over the next decade due to patterns of sexual behaviour,
      drug use, migration, and the sociocultural practices and legal and religious
      taboos which serve as barriers to safe sex, as well as stigma, shame, and denial
      which preclude many issues from being openly discussed and addressed. Studying
      the HIV epidemic in the Caribbean Basin is difficult, as efforts to synthesize
      information are often hampered by a lack of uniformity and availability of
      surveillance data in many parts of the region. In addition, behavioural
      surveillance is limited, and interventions addressing the cultural context of
      Caribbean populations are few in number. Overall, the geographic, political,
      cultural, and linguistic diversity of the Caribbean underscores the complexity of
      understanding broader regional patterns of HIV infection and developing and
      implementing targeted and appropriate responses.

PMID- 16096112
TI  - Pharmacogenetics in drug regulation: promise, potential and pitfalls.
AB  - Pharmacogenetic factors operate at pharmacokinetic as well as pharmacodynamic
      levels-the two components of the dose-response curve of a drug. Polymorphisms in
      drug metabolizing enzymes, transporters and/or pharmacological targets of drugs
      may profoundly influence the dose-response relationship between individuals. For
      some drugs, although retrospective data from case studies suggests that these
      polymorphisms are frequently associated with adverse drug reactions or failure of
      efficacy, the clinical utility of such data remains unproven. There is,
      therefore, an urgent need for prospective data to determine whether pre-treatment
      genotyping can improve therapy. Various regulatory guidelines already recommend
      exploration of the role of genetic factors when investigating a drug for its
      pharmacokinetics, pharmacodynamics, dose-response relationship and drug
      interaction potential. Arising from the global heterogeneity in the frequency of
      variant alleles, regulatory guidelines also require the sponsors to provide
      additional information, usually pharmacogenetic bridging data, to determine
      whether data from one ethnic population can be extrapolated to another. At
      present, sponsors explore pharmacogenetic influences in early clinical
      pharmacokinetic studies but rarely do they carry the findings forward when
      designing dose-response studies or pivotal studies. When appropriate, regulatory
      authorities include genotype-specific recommendations in the prescribing
      information. Sometimes, this may include the need to adjust a dose in some
      genotypes under specific circumstances. Detailed references to pharmacogenetics
      in prescribing information and pharmacogenetically based prescribing in routine
      therapeutics will require robust prospective data from well-designed studies.
      With greater integration of pharmacogenetics in drug development, regulatory
      authorities expect to receive more detailed genetic data. This is likely to
      complicate the drug evaluation process as well as result in complex prescribing
      information. Genotype-specific dosing regimens will have to be more precise and
      marketing strategies more prudent. However, not all variations in drug responses
      are related to pharmacogenetic polymorphisms. Drug response can be modulated by a
      number of non-genetic factors, especially co-medications and presence of
      concurrent diseases. Inappropriate prescribing frequently compounds the
      complexity introduced by these two important non-genetic factors. Unless
      prescribers adhere to the prescribing information, much of the benefits of
      pharmacogenetics will be squandered. Discovering highly predictive genotype
      phenotype associations during drug development and demonstrating their clinical
      validity and utility in well-designed prospective clinical trials will no doubt
      better define the role of pharmacogenetics in future clinical practice. In the
      meantime, prescribing should comply with the information provided while
      pharmacogenetic research is deservedly supported by all concerned but without
      unrealistic expectations.

PMID- 16096115
TI  - Emerging linkages between substance abuse and HIV infection in St. Croix, US
      Virgin Islands.
AB  - In the US Virgin Islands 575 cases of AIDS had been reported to the Centers for
      Disease Control and Prevention through mid-2003. Although males continue to be
      most affected by HIV/AIDS, the feminization of the epidemic is evidenced by
      recent data showing rates of infection increasing rapidly among women. This paper
      focuses on the role of substance abuse and the socially and culturally based
      gender issues that influence risk and vulnerability to HIV in this setting. 254
      chronically drug- or alcohol-involved men and women were recruited and
      interviewed using targeted sampling strategies. Crack use was overwhelmingly
      reported by females when compared to males (84.7% vs. 48.8%). Women also reported
      a significantly higher number of sexual partners in the past month (5.6 vs. 2.3)
      and significantly more occasions of unprotected vaginal sexual contact (11.2 vs.
      6.5). Rates of self-reported HIV infection were elevated among women as well
      (8.8% vs. 1.4%). Women's precarious economic position and lack of access to
      legitimate income-generating activities tended to drive them into 'survival sex'
      to support their subsistence and drug needs. As such, it would appear that
      substance abuse has an emerging role in the spread of the epidemic in St. Croix,
      particularly among women.

PMID- 16096116
TI  - Sexual risks and concerns about AIDS among adolescents in Anguilla.
AB  - Concerns regarding HIV/AIDS infection and the health risk behaviours among youth
      in the Caribbean are growing. Considering that approximately 30% of the
      Caribbean's population falls between the ages of 10 to 24, there is considerable
      need for research on youth in this region. This paper reports findings regarding
      the sexual risks and concerns about AIDS among 1,225 enrolled school students in
      Anguilla, drawn from self-administered health surveys conducted in 2002. Although
      over 40% of youth reported lifetime alcohol use, experience with other drugs was
      moderate. Males initiated sexual activity at a much younger median age than
      females (11 years for males vs. 14 years for females), and were twice as likely
      to have had sexual intercourse. In a multivariate logistic regression model,
      being sexually active was predicted by male gender (p=.000), recent substance use
      (p=.000), recent depression (p=.018), and a history of physical (p=.025) and
      sexual (p=.000) abuse. Only 22% of sexually active youth under 12 years of age
      reported using condoms at last intercourse, compared to 71% of those 13 and over.
      Older sexually active youth were also much more likely than younger ones to
      express ongoing concern about becoming infected with HIV. Implications for needed
      HIV/AIDS-prevention interventions are discussed.

PMID- 16096117
TI  - Quality of parent-child relationship and adolescent HIV risk behaviour in St.
      Maarten.
AB  - The highest incidence rates of HIV/AIDS in the Caribbean are recorded in
      heterosexual and youth populations. With sparse prevention and intervention
      programmes in place, there is a pressing need to address the HIV/AIDS risk of
      youth. The objective of this analysis was to describe the extent of youth risk
      behaviour in St. Maarten and explore the relationship between quality of parental
      child relationship and adolescent HIV risk behaviours. The sample consisted of
      1,078 students (age range 14-18, mean 15.6 (s.d. 1.7). The data were collected by
      self-report survey in the Spring of 2001 in the classrooms of all seven secondary
      schools in St. Maarten. The survey instrument included demographic information,
      and used questions derived from the Center for Disease Control's (CDC) Youth Risk
      Behavior Survey (YRBS) to assess health risk behaviour prevalence, including
      tobacco, alcohol, and drug use, and sexual activity. The survey also asked youth
      to rate their relationship with their parents. Analysis showed a relatively high
      rate of risk behaviour in this school population. Multi-variate analysis showed
      that a 'great' relationship with both parents, as perceived by the student, was
      significantly associated with lower rates of tobacco and alcohol use as well as
      lower rates of sexual activity.

PMID- 16096118
TI  - Violence against substance-abusing South African sex workers: intersection with
      culture and HIV risk.
AB  - The Republic of South Africa has become an epicentre of heterosexual HIV
      transmission among Black women, and the interface between violence against women,
      substance abuse, and HIV risk is becoming evident. This paper describes the
      characteristics of Black South African women who engage in sex work in Pretoria
      and examines their intersecting experiences of high-risk sexual behaviour,
      substance abuse, and victimization. Ninety-three women were recruited into the
      study. Field staff collected biological measures of drug use and administered a
      structured, self-report interview. Findings indicate that young South African
      women who engage in sex work and use drugs rely on this activity as their main
      source of income and are supporting other family members. The majority of sample
      women reported experiencing some victimization at the hand of men, either clients
      or boyfriends, with many reporting childhood abuse histories; young women also
      report great fear of future victimization. Findings also suggest that as a result
      of their decreased likelihood of using protection, women who reported any sexual
      or physical victimization are at increased risk for HIV and other STIs. Results
      support the critical need for targeted, comprehensive interventions that address
      substance abuse, sexual risk, and violence as interrelated phenomena.

PMID- 16096119
TI  - Heroin and HIV risk in Dar es Salaam, Tanzania: youth hangouts, mageto and
      injecting practices.
AB  - HIV risk through needle sharing is now an emerging phenomenon in Africa. This
      article describes the practices that heroin users are producing as they establish
      the rules and organization surrounding their drug use. Their practices and
      interactions reveal the ways that they become initiated into its use, how they
      progress to injecting, and the important role of local neighbourhood hangouts in
      facilitating this process. Their practices, interactions and narratives also
      provide insights into what may be the most appropriate HIV-prevention
      interventions. Semi-structured interviews were conducted during the months of
      February and July 2003 with 51 male and female injectors residing in 8
      neighbourhoods in the Dar es Salaam, Tanzania. Interviews were content coded and
      codes were collapsed into emergent themes around hangout places, initiation of
      heroin use, and progression to injecting. Interviews reveal that Dar es Salaam
      injectors begin smoking heroin in hangout areas with their friends, either
      because of peer pressure, desire, or trickery. One hangout place in particular,
      referred to as the 'geto' (ghetto) is the main place where the organization and
      rules governing heroin use are produced. Three main types of heroin 'ghettoes'
      are operating in Dar es Salaam. As users build a tolerance for the drug they move
      along a continuum of practices until they begin to inject. Injecting heroin is a
      comparatively recent practice in Africa and coincides with: (1) Tanzania
      transitioning to becoming a heroin consuming community; (2) the growing
      importance of youth culture; (3) the technical innovation of injecting practices
      and the introduction and ease of use of white heroin; and (4) heroin smokers,
      sniffers, and inhalers perceived need to escalate their use through a more
      effective and satisfying form of heroin ingestion.

PMID- 16096120
TI  - Tailoring an HIV-prevention intervention for cocaine injectors and crack users in
      Porto Alegre, Brazil.
AB  - Brazil has the second largest number of reported AIDS cases in the world. Porto
      Alegre, like most other large urban centres in Brazil, has been greatly impacted
      by an AIDS epidemic driven by high rates of drug use and risky sexual behaviours.
      While epidemiologic surveillance of HIV/AIDS and treatment initiatives for HIV
      infected individuals are well developed in Brazil, comparatively little attention
      has focused on developing interventions directed toward high-risk populations.
      Intervention programmes, particularly those tailored for chronic drug users, are
      lacking. This pilot project successfully adapted and tailored a cognitive
      behavioural HIV intervention developed in the US to the cultural setting in Porto
      Alegre. The project established feasibility and acceptability of the approach for
      targeting risky drug and sexual behaviours among a group of male Brazilian drug
      users. A sample of 120 male cocaine users was recruited from a public health
      clinic serving the target population in the city of Porto Alegre. The average age
      of the participants was 29; they averaged less than 8 years of formal education;
      and less than half (41%) were married. Lifetime self-reported drug use was high
      with 93% reporting cocaine use, 87% reporting crack use, and 100% reporting
      marijuana use. 43% of the sample reported ever injecting drugs. Reports of risky
      sexual behaviours were similarly elevated. Almost half (45%) tested positive for
      HIV. Preliminary evidence suggests that intervention acceptability was high among
      participants. Given the reported high risk sexual and drug use behaviours among
      these men, HIV interventions must be evaluated and expanded to include this
      population as well as their sexual partners.

PMID- 16096121
TI  - The effect of serostatus on HIV risk behaviour change among women sex workers in
      Miami, Florida.
AB  - HIV prevention and risk reduction are especially salient and timely issues for
      women, particularly among those who are drug-involved or who exchange sex for
      drugs or money. Studies suggest that HIV-prevention measures can be effective
      with highly vulnerable women, and have the potential to produce significant
      reductions in risk behaviours among both HIV-negative and HIV-positive women.
      Within this context, this paper examines risk behaviours and HIV serostatus among
      407 drug-involved women sex workers in Miami, Florida, and investigates the
      effects of participation in HIV testing, counselling, and a risk-reduction
      intervention on subsequent behavioural change among this population. Overall, at
      follow-up, the HIV-positive women were 2.4 times more likely than the HIV
      negative women to have entered residential treatment for drug abuse, 2.2 times
      more likely to have decreased the number of their sex partners, 1.9 times more
      likely to have decreased the frequency of unprotected sex, 1.9 times more likely
      to have reduced their levels of alcohol use, and 2.3 times more likely to have
      decreased their crack use. These data support the importance of HIV testing and
      risk-reduction programmes for drug-involved women sex workers.

PMID- 16096122
TI  - Micro-social structural approaches to HIV prevention: a social ecological
      perspective.
AB  - To be effective and sustainable, HIV-prevention interventions need to be
      sufficiently powerful to counteract prevailing social norms and diffuse through
      the targeted community to provide social reinforcement for behaviour change.
      Social structural and environmental factors are major influences on HIV-related
      behaviours yet the dearth of conceptualization and operationalization of these
      factors impede progress in intervention development. In this paper we propose a
      social ecological perspective to intervention and highlight relevant theories
      from social psychology and organizational behaviour literatures. We examine
      social networks and social settings as micro-structural and environmental
      influences on HIV risk behaviours, social identities and norms, and as important
      targets for HIV-prevention intervention. Intervention approaches are proposed
      that target networks and behavioural settings and provide participants with
      socially meaningful and rewarding behavioural options that are consistent with
      valued prosocial identities or roles. Examples are presented on how such an
      approach has been utilized in prior HIV prevention interventions, including our
      social network-oriented intervention that trained disadvantaged former and
      current illicit drug users to conduct peer outreach. We describe how behavioural
      interventions may enhance or introduce new prosocial identities and social roles,
      and that network members may confer social approval to reinforce these identities
      and roles, leading to sustained behavioural risk reduction and changes in risk
      behaviour norms.

PMID- 16096123
TI  - Alcohol and suicide at the population level--the Canadian experience.
AB  - Studies suggest that the population level link between alcohol and suicide
      differs across countries and between men and women. The aim of this paper was to
      estimate the relationship between alcohol consumption and suicide in Canada and
      to put the results in a comparative perspective. The relationship was elucidated
      for whole Canada, different provinces and also separately for men and women. The
      total suicide rate in Canada increased significantly by around 4% as alcohol
      consumption increased by one litre per capita, suggesting that approximately 25 -
      30% of Canadian suicides were related to alcohol. The relationship was stronger
      for women than for men. A significant effect was found in all provinces except
      from Quebec, but the overall regional variation was not statistically
      significant. In an international perspective, the relationship for women was
      somewhat weaker than in Sweden and Norway, but larger than in Finland, the United
      States and Southern European countries. For men, the association was similar to
      what is found in the United States and Finland, weaker than in Sweden, Norway and
      Russia but stronger than in Southern European countries. The results only partly
      support the idea that intoxication frequency explains national differences in
      this relationship. Possible explanations for the stronger association among women
      are also discussed.

PMID- 16096124
TI  - Therapy preference and treatment outcome in clients with mild to moderate alcohol
      dependence.
AB  - The Brief Treatment Programme for Alcohol Dependence allocated 122 clients
      randomly to three different forms of brief therapy. Prior to allocation clients
      were asked what their preference would have been had allocation not been random.
      This study posed the question: did clients receiving their preferred treatment
      have a better outcome than those who did not? Also examined were differences in
      the treatment process variables of perceived effectiveness, satisfaction,
      rapport, engagement and number of sessions attended. The results were that there
      was no difference in either outcome or treatment process according to whether or
      not clients were allocated to their treatment of preference. It is concluded that
      these findings reinforce both the ethicality of the randomized controlled trial
      as a methodology for examining differential treatment outcomes in individual
      brief treatment of between one and five sessions for alcohol dependence and the
      validity of these findings as they might relate to real clinical settings.
      Finally, it is suggested that other researchers consider the inclusion of
      questions related to client preference.

PMID- 16096125
TI  - Validation of the World Health Organization Alcohol, Smoking and Substance
      Involvement Screening Test (ASSIST): report of results from the Australian site.
AB  - The concurrent, construct, discriminative and predictive validity of the World
      Health Organization's Alcohol Substance Involvement Screening Test (ASSIST) were
      examined in an Australian sample. One hundred and fifty participants, recruited
      from drug treatment (n = 50) and primary health care (PHC) settings (n = 100),
      were administered a battery of instruments at baseline and a modified battery at
      3 months. Measures included the ASSIST; the Addiction Severity Index-Lite (ASI
      Lite); the Severity of Dependence Scale (SDS); the MINI International
      Neuropsychiatric Interview (MINI-Plus); the Rating of Injection Site Condition
      (RISC); the Drug Abuse Screening Test (DAST); the Alcohol Use Disorders
      Identification Test (AUDIT); the Revised Fagerstrom Tolerance Questionnaire
      (RTQ); and the Maudsely Addiction Profile (MAP). Concurrent validity was
      demonstrated by significant correlations between ASSIST scores and scores from
      the ASI-lite, SDS, AUDIT and DAST; and significantly greater ASSIST scores for
      those with diagnoses of abuse or dependence. Construct validity was established
      by significant correlations between ASSIST scores and measures of risk factors
      for the development of drug and alcohol problems. Participants diagnosed with
      attention deficit/hyperactivity disorder or antisocial personality disorder had
      significantly higher ASSIST scores than those not diagnosed as such.
      Discriminative validity was established by the capacity of the ASSIST to
      discriminate between substance use, abuse and dependence. ROC analysis was able
      to establish cut-off scores for an Australian sample, with suitable specificities
      and sensitivities for most substances. Predictive validity was demonstrated by
      similarity in ASSIST scores obtained at baseline and at follow-up. The findings
      demonstrated that the ASSIST is a valid screening test for psychoactive substance
      use in individuals who use a number of substances and have varying degrees of
      substance use.

PMID- 16096126
TI  - Estimating the dollar value of the illicit market for cannabis in New Zealand.
AB  - New data collected on the procurement and purchase of cannabis in the 2001 New
      Zealand National Drug Survey are used to estimate the dollar value of the illicit
      market for cannabis as well conduct other economic analyses of the illicit
      purchase of cannabis in New Zealand. Eighty-four per cent of last-year cannabis
      users received at least some of their cannabis 'free', 38% 'bought' at least some
      of their cannabis, while only 8% grew any of their supply. By proportion of the
      total dollar value of the cannabis market, sales of 'tinnies' (1.5 g) had the
      biggest share of the market (30%), followed closely by 50 NZ dollars bags (4 g)
      (29%) and ounces (28 g) (26%). The average price paid per gram of cannabis fell
      steadily from 20.50 NZ dollars per gram for a joint to 5.63 per gram for a pound
      (NZ dollars). The distribution of spending on cannabis was positively skewed
      (average 1313 NZ dollars, median 400 NZ dollars, mode 100, range 5 - 55,200,
      interquartile range 100 - 1200) (NZ dollars). The bottom 50% of cannabis buyers
      spent a median amount on cannabis of 100 NZ dollars a year while the top 5% spent
      a median amount of 7425 a year (NZ dollars). The dollar value of the illicit
      cannabis market was estimated to be 190 million (131 - 249 million) (NZ dollars).
      Three limitations are acknowledged with the market estimate calculated: (i) the
      truncated age range of the survey data (13 - 45 years); (ii) the likely
      underestimation of heavy cannabis use in household drug surveys; (iii) a degree
      of 'double-counting' when the same cannabis is bought and sold a number of times.

PMID- 16096127
TI  - Smoking cessation interventions in Australian drug treatment agencies: a national
      survey of attitudes and practices.
AB  - A cross-sectional survey was mailed to all Australian drug and alcohol treatment
      agencies to assess their smoking cessation policies and practices and related
      staff attitudes. Barriers to smoking cessation interventions were also examined.
      Completed questionnaires were returned by 213 managers and 204 other staff
      representing 260 agencies (59.8% consent rate). Approximately one-quarter of
      agencies have smoking cessation intervention policies and one-third of clients
      receive adequate smoking advice. Of 12 intervention strategies, only the
      recording of smoking status on file occurs in a majority of cases. Concerns about
      the potential negative impact of smoking interventions and lack of client
      interest were endorsed as very important barriers by the highest percentage of
      respondents. 12.6% of managers and 16.5% of other staff agreed that it is
      occasionally useful for staff to smoke with a client. Smoking cessation receives
      little systematic attention from drug and alcohol agencies. Training and policy
      initiatives are needed urgently to address negative staff attitudes impeding
      progress in this area.

PMID- 16096128
TI  - Exploring the relationship between homelessness and risk factors for heroin
      related death--a qualitative study.
AB  - The aim of this study was to explore the relationship between housing status,
      associated social networks and risk factors for heroin-related death. We used
      semi-structured face-to-face qualitative interviews, recorded, transcribed and
      analysed thematically by framework techniques at three centres providing services
      to homeless people in a large cosmopolitan city. Different types of accommodation
      for homeless people have differing social cultures which have an impact upon the
      amount of heroin used, likelihood of injecting alone or likelihood of achieving
      abstinence. Hostel accommodation appeared to be linked with a culture of group
      injecting, which tends to increase the amount of heroin taken. Those with
      experience of rough sleeping described heroin use to ameliorate the uncomfortable
      realities of outdoor sleeping, although the overall amount used tended to be less
      due to having less money to spend on drugs. The prison setting was described as a
      setting where heroin use was reduced or stopped. Moving away from homelessness
      towards sustaining an independent tenancy appeared to be associated with a move
      towards solitary use. We postulate that a progression towards solitary use in a
      housed environment is one explanation for previous research findings showing the
      average age of heroin-related death to be increasing despite a decrease in the
      average age of initiation into heroin use. Hostel accommodation should form a
      priority setting for future health promotion interventions aimed to reduce heroin
      related death. They appear to be linked with an increase in heroin use in the
      presence of a third party. Drug users sleeping rough in cold climates need to be
      made aware of the dangers of medicating with heroin to address problems of
      insomnia due to cold weather.

PMID- 16096129
TI  - The medical complications of alcohol use: understanding mechanisms to improve
      management.
AB  - The use of alcohol in a dependent or even a regular heavy pattern predisposes the
      drinker to a range of adverse consequences. These include a risk of direct harm
      from alcohol, including organ damage, mental health disorders and a range of
      social and legal problems associated with behaviours due to alcohol's effects.
      The range of organ damage associated with regular heavy alcohol consumption is
      well described. Much new information on the mechanisms by which damage occurs is
      available and is reviewed in this paper. New knowledge can assist in the
      development of more appropriate management strategies for those affected by the
      medical complications of alcohol use. Genetic susceptibility to tissue injury is
      explored and the reasons why many heavy drinkers do not appear to experience
      organ damage are considered. Approaches to the management of certain alcohol
      related disorders are outlined.

PMID- 16096130
TI  - From opioid maintenance to abstinence: a literature review.
AB  - It appears that the literature on agonist maintenance therapies for opioid
      dependence pays more attention to outcomes during, rather than after, treatment.
      This review aims to (a) estimate to what extent opioid abstinence can be expected
      from former maintenance patients, (b) examine possible relationships between
      patient and treatment characteristics and abstinence rates and (c) assess the
      need for research in the field of abstinence-orientated maintenance treatment in
      general, and time-limited buprenorphine maintenance treatment in particular.
      Database searches supplemented by cross-references resulted in 12 studies
      included in the review. The studies were mostly naturalistic follow-up studies of
      former methadone maintenance patients, authored by US researchers in the 1970s.
      Buprenorphine was used in only one of the studies, and then as a transition
      between methadone and abstinence. There were considerable variations in
      definition and assessment of abstinence. Pooled abstinence rates ranged from 22%
      to 86%. The single factor associated most frequently with abstinence was
      voluntary participation in detoxification programmes with eligibility criteria
      ('therapeutic detoxification'). When 'therapeutic detoxification' was compared to
      'non-therapeutic detoxification' the pooled abstinence rates were 48% and 22%,
      respectively. Abstinence-orientated maintenance therapy may be suitable for a
      subgroup of patients, but there is a substantial need for research updates.

PMID- 16096131
TI  - Enabling environments and the reduction of drug-related harm: re-framing
      Australian policy and practice.
AB  - In this paper Moore & Dietze use data from their study of street-based injecting
      drug users and sex workers in the Melbourne suburb of St Kilda to challenge the
      dominant emphasis of drug policy in Australia. They remind us that while existing
      harm reduction strategies that encourage individual behaviour change should be
      continued, these measures need to be complemented and extended by further
      attention to the environmental aspects of drug-related harm. This is a timely
      call. Responses targeting individual behaviour change are relatively easy to
      implement and less politically challenging. However, if we are really serious
      about reducing drug-related harm in the Australian community, then broader
      systemic and structural barriers which undermine these efforts must be
      addressed.Simon LentonEditor, Harm Reduction Digest.

PMID- 16096132
TI  - The first methadone clinic in Beijing.

PMID- 16096134
TI  - Proximate and mineral composition of crab meat consumed in Bahrain.
AB  - The proximate, mineral and heavy metals of raw and cooked crab meat, Portunus
      pelagicus, consumed in Bahrain were studied. The crab meat contains a good level
      of protein (17.5-18.8%), with very low proportion of fat (0.6-1.4%). The levels
      of sodium, potassium, calcium and phosphorus were found to be higher than other
      minerals. Traces of heavy metals (lead, mercury, cadmium) were also reported.
      Traditional cooking had a considerable effect on proximate and mineral contents
      of crab meat.

PMID- 16096135
TI  - Is there an association between the nutritional status of the mother and that of
      her 2-year-old to 5-year-old child?
AB  - The aim of this study was to determine whether there is an association between
      the nutritional status of the mother and that of her 2-year-old to 5-year-old
      child in a rural village in South Africa where there is a high prevalence of
      childhood malnutrition (in particular, deficiencies of vitamin A and iron) and of
      maternal obesity. A blood sample and anthropometric measurements were obtained
      for 118 child-mother pairs. There was a positive mother-child correlation for
      serum ferritin (R=0.2304, P<0.05) and haemoglobin (R=0.2664, P<0.01)
      concentrations, respectively. The child of an anaemic mother had a relative risk
      of 1.632 of also being anaemic. There was no mother-child association for either
      serum retinol concentration or anthropometric measurements. Serum retinol
      concentrations showed a positive correlation with both serum ferritin (mothers
      only; R=0.2161, P<0.01) and haemoglobin (R=0.2807, P<0.01 for mothers; and
      R=0.2710, P < 0.01 for children) concentrations. The mother-child association for
      iron status is probably because of an inadequate dietary intake and low
      bioavailability of dietary iron, which are major causes of iron deficiency. The
      lack of mother-child association for serum retinol concentration could probably
      be ascribed to the fact that children are more susceptible to vitamin A
      deficiency than adults because of childhood diseases.

PMID- 16096136
TI  - Food for two seasons: culinary uses of non-cultivated local vegetables and
      mushrooms in a south Italian village.
AB  - The use of non-cultivated plants in a daily diet based on local cuisines is
      potentially of considerable interest to nutritional scientists, because of the
      plants' role as local products and their potential as sources of novel
      nutraceuticals. In many Mediterranean regions these traditions are at risk of
      disappearing, hence the urgent need to study such knowledge systems. Accordingly,
      an ethnobotanical survey was carried out among the 850 inhabitants of the village
      of Castelmezzano, in central Lucania, which is located in the inland southern
      Italy. Seventy-five taxa of non-cultivated and semi-cultivated local food plants
      and mushrooms were documented, and uncommon food uses of a few species were
      reported for the first time. These include Bellavalia romana, Lepista nebularis
      and Onopordum illyricum. Most of the recorded non-cultivated food plants and
      mushrooms are cooked in oil or fat. Very few are consumed raw. This article
      discusses in detail the traditional culinary uses of these plants, their
      seasonality, ethnoecology, and their economic and nutritional potentials. The
      article also demonstrates how food agro-biodiversity is inextricably connected
      with cultural heritage.

PMID- 16096137
TI  - Infant food from quality protein maize and chickpea: optimization for preparing
      and nutritional properties.
AB  - The present study had two objectives: to determine the best combination of
      nixtamalized maize flour (NMF) from quality protein maize and extruded chickpea
      flour (ECF) for producing an infant food, and to evaluate the nutritional
      properties of the optimized NMF/ECF mixture and the infant food. Response surface
      methodology (RSM) was applied to determine the best combination of NMF/ECF; the
      experimental design (Lattice simplex) generated 11 assays. Mixtures from each
      assay were evaluated for true protein and available lysine. Each one of 11
      mixtures was used for preparing 11 infant foods that were sensory evaluated for
      acceptability. A common optimum value for the three response variables was
      obtained utilizing the desirability method. The best combination of NMF/ECF for
      producing an infant food was NMF = 26.7%/ECF = 73.3%; this optimized mixture had
      a global desirability of 0.87; it contained 19.72% dry matter (DM) proteins,
      6.10% (DM) lipids, 71.45% (DM) carbohydrates, and 2.83% (DM) minerals; its
      essential amino acids profile covered the amino acids requirements for children
      10-12 years old. The infant food prepared from optimized mixture had an in vitro
      protein digestibility of 87.9%, and a calculated protein efficiency ratio of
      1.86. Infant food could be used to support the growth of infants in developing
      countries.

PMID- 16096138
TI  - Phenolic contents and antioxidant activity of some food and medicinal plants.
AB  - To identify promising sources of antioxidants, some food and medicinal plants
      were studied for total phenolic contents and antioxidant activity. The leaves,
      bark and fruits of Terminalia arjuna, Terminalia bellerica, Terminalia chebula
      and Terminalia muelleri, the leaves and fruits of Phyllanthus emblica, and the
      seeds of Syzygium cumini were found to have high total phenolic contents (72.0
      167.2 mg/g) and high antioxidant activity (69.6-90.6%). Leaves of
      Eucalyptusglobulus were a rich source of rutin, Moringa oleifera for kaempferol,
      aerial parts of Centella asiatica for quercetin, fruits of T. bellerica and T.
      chebula for gallic acid, and bark of T. arjuna, leaves and fruits of T. bellerica
      and bark, leaves and fruits of T. muelleri for ellagic acid.

PMID- 16096139
TI  - In vitro evaluation of iron solubility and dialyzability of various iron
      fortificants and of iron-fortified milk products targeted for infants and
      toddlers.
AB  - The objectives of the present study were: to compare the solubility and
      dialyzability of various iron fortificants (iron pyrophosphate, ferrous bis
      glycinate, ferrous gluconate, ferrous lactate, ferrous sulfate) added, in the
      presence of ascorbic acid, to pasteurized milk samples produced under laboratory
      conditions; and to compare the solubility and dialyzability of iron in commercial
      pasteurized, UHT and condensed milk products available in the Greek market
      fortified with various vitamins and minerals including iron and targeted towards
      infants (6-12 months old) and toddlers. Iron solubility and dialyzability were
      determined using a simulated gastrointestinal digestive system. Ferrous
      dialyzable iron (molecular weight lower than 8000) was used as an index for
      prediction of iron bioavailability. Ferrous dialyzable iron in pasteurized milk
      samples fortified with iron pyrophosphate, ferrous lactate and ferrous bis
      glycinate was higher (P < 0.05) than that in milk samples fortified with ferrous
      sulfate and ferrous gluconate. In commercial liquid pasteurized or UHT milk
      products, formation of ferrous dialyzable iron in products fortified with ferrous
      lactate was not different (P > 0.05) from those fortified with ferrous sulfate.
      Ferrous dialyzable iron in four condensed commercial milk products was higher (P
      < 0.05) than the corresponding values of the liquid UHT milk samples fortified
      with the same fortificant (ferrous sulfate). Ferrous dialyzable iron was higher
      (P < 0.05) in products targeted for infants compared with those targeted for
      toddlers. In conclusion, the type of iron source, milk processing and the overall
      product composition affect formation of ferrous dialyzable iron and may determine
      the success and effectiveness of iron fortification of milk.

PMID- 16096140
TI  - Changing the culture: interprofessional education for collaborative patient
      centred practice in Canada.

PMID- 16096142
TI  - Interprofessionality as the field of interprofessional practice and
      interprofessional education: an emerging concept.
AB  - This paper proposes a new concept and a frame of reference that should permit the
      development of a better understanding of a phenomenon that is the development of
      a cohesive and integrated health care practice among professionals in response to
      clients' needs. The concept is named "interprofessionality" and aims to draw a
      clear distinction with another concept, that of interdisciplinarity. The
      utilization of the concept of interdisciplinarity, which originally concerns the
      development of integrated knowledge in response to fragmented disciplinary
      knowledge, has caused some confusion. We need a concept that will specifically
      concern the development of a cohesive practice among different professionals from
      the same organization or from different organizations and the factors influencing
      it. There is no concept that focuses clearly on this field. Interprofessionality
      concerns the processes and determinants that influence interprofessional
      education initiatives as well as determinants and processes inherent to
      interprofessional collaboration. Interprofessionality also involves analysis of
      the linkages between these two spheres of activity. An attempt to bridge the gap
      between interprofessional education and interprofessional practice is long
      overdue; the two fields of inquiry need a common basis for analysis. To this end,
      we propose a frame of reference, an interprofessional education for collaborative
      patient-centred practice framework. The framework establishes linkages between
      the determinants and processes of collaboration at several levels, including
      links among learners, teachers and professionals (micro level), links at the
      organizational level between teaching and health organizations (meso level) and
      links among systems such as political, socio-economic and cultural systems (macro
      level). Research must play a key role in the development of interprofessionality
      in order to document these linkages and the results of initiatives as they are
      proposed and implemented. We also believe that interprofessionality will not be
      pursued without the requisite political will.

PMID- 16096143
TI  - Key elements for interprofessional education. Part 1: the learner, the educator
      and the learning context.
AB  - This paper is the first of two that highlights key elements needed for
      consideration in the planning and implementation of interprofessional educational
      (IPE) interventions at both the pre and post-licensure qualification education
      levels. There is still much to be learned about the pedagogical constructs
      related to IPE. Part 1 of this series discusses the learning context for IPE and
      considers questions related to the "who, what, where, when and how" related to
      IPE. Through a systematic literature review that was conducted for Health Canada
      in its move to advance Interprofessional Education for Patient Centred Practice
      (IECPCP), this paper provides background information that can be helpful for
      those involved in an interprofessional initiative. A historical review of IPE
      sets the international context for this area and reflects the work that has been
      done and is currently being initiated and implemented to advance IPE for health
      professional students. Much can be learned from the literature related to the
      pedagogical approaches that have been tried and the issues that need to be
      addressed related to the learner, the educator and the learning context which
      this paper examines.

PMID- 16096144
TI  - Key elements of interprofessional education. Part 2: factors, processes and
      outcomes.
AB  - In the second paper of this two part series on Key Elements of Interprofessional
      Education (IPE), we highlight factors for success in IPE based on a systematic
      literature review conducted for Health Canada in its "Interprofessional Education
      for Patient Centred Practice" (IECPCP) initiative in Canada (Oandasan et al.,
      2004). The paper initially discusses micro (individual level) meso
      (institutional/organizational level) and macro (socio-cultural and political
      level) factors that can influence the success of an IPE initiative. The
      discussion provides the infrastructure for the introduction of a proposed
      framework for educators to utilize in the planning and implementation of an IPE
      program to enhance a learner's opportunity to become a collaborative
      practitioner. The paper also discusses key issues related to the evaluation of
      IPE and its varied outcomes. Lastly, it gives the reader suggestions of outcome
      measurements that can be used within the proposed IPE framework.

PMID- 16096145
TI  - A blueprint for interprofessional learning.
AB  - Interprofessional education (IPE) has been promoted as a method to enhance the
      ability of health professionals to learn to work together. This article examines
      several approaches to learning that can help IPE fulfill its expectations. The
      first is aimed at the transfer of learning novel situations and involves two
      ideas. Students need to be challenged with progressively more complex tasks and
      those tasks need to reflect the reality in which they will be working. Second,
      the learning situation needs to be structured using the five elements of best
      practice cooperative learning: positive interdependence, face-to-face promotive
      interaction, individual accountability, interpersonal and small-group skills, and
      group processing. Finally, the learning process itself needs to be approached
      from an experiential learning framework cycling through the four-stage model of
      planning, doing, observing and reflecting. By using increasingly complex and
      relevant cases in cooperative groups with an experiential learning process
      interprofessional education can be successful.

PMID- 16096146
TI  - Learning together to teach together: interprofessional education and faculty
      development.
AB  - Interprofessional education for collaborative patient-centered practice has been
      identified as a key mechanism to address health care needs and priorities.
      Faculty development can play a unique role in promoting interprofessional
      education (IPE) by addressing some of the barriers to teaching and learning that
      exist at both the individual and the organizational level, and by providing
      individuals with the knowledge and skills needed to design and facilitate IPE.
      This article highlights a number of approaches and strategies that can facilitate
      IPE. In particular, it is recommended that faculty development initiatives aim to
      bring about change at the individual and the organizational level; target diverse
      stakeholders; address three main content areas, notably interprofessional
      education and collaborative patient-centred practice, teaching and learning, and
      leadership and organizational change; take place in a variety of settings, using
      diverse formats and educational strategies; model the principles and premises of
      interprofessional education and collaborative practice; incorporate principles of
      effective educational design; and consider the adoption of a dissemination model
      to implementation. Clearly, faculty members play a critical role in the teaching
      and learning of IPE and they must be prepared to meet this challenge.

PMID- 16096147
TI  - Academic administrators' attitudes towards interprofessional education in
      Canadian schools of health professional education.
AB  - Interprofessional education is an approach to educating and training students and
      practitioners from different health professions to work in a collaborative manner
      in providing client and/or patient-centred care. The introduction and successful
      implementation of this educational approach is dependent on a variety of factors,
      including the attitudes of students, faculty, senior academic administrators
      (e.g., deans and directors) and practitioners. The purpose of this study was to
      examine attitudes towards interprofessional teamwork and interprofessional
      education amongst academic administrators of post-secondary health professional
      education programs in Canada. A web-based questionnaire in English and French was
      distributed via e-mail messaging during January 2004 to academic administrators
      in Canada representing medicine, nursing, pharmacy, social work, occupational
      therapy and physiotherapy post-secondary educational programs. Responses were
      sought on attitudes towards interprofessional teamwork and interprofessional
      education, as well as opinions regarding barriers to interprofessional education
      and subject areas that lend themselves to interprofessional education. In
      general, academic administrators responding to the survey hold overall positive
      attitudes towards interprofessional teamwork and interprofessional education
      practices, and the results indicate there were no significant differences between
      professions in relation to these attitudinal perspectives. The main barriers to
      interprofessional education were problems with scheduling/calendar, rigid
      curriculum, turf battles and lack of perceived value. The main pre-clinical
      subject areas which respondents believed would lend themselves to
      interprofessional education included community health/prevention, ethics,
      communications, critical appraisal, and epidemiology. The results of this study
      suggest that a favourable perception of both interprofessional teamwork and
      interprofessional education exists amongst academic administrators of Canadian
      health professional education programs. If this is the case, the post-secondary
      system in Canada is primed for the introduction of interprofessional education
      initiatives which support the development of client and patient-centred
      collaborative practice competencies.

PMID- 16096148
TI  - Interprofessional learning and higher education structural barriers.
AB  - Structural changes need to be made within universities such that
      interprofessional education for patient-centred collaborative practice becomes a
      responsibility that crosses faculty jurisdictions and is accepted as the
      responsibility of all associated health and human service programs. In
      communities, the patient or client is the centre of professional attention
      requiring care that goes beyond the skill and scope of any one profession.
      Notions about collaboration inform and drive interprofessional education and
      should lead to sustainable system changes within centres of advanced education
      that ensure a permanent place for interprofessional education in all health and
      human service programs. This chapter explores the many barriers to achieving this
      goal, and offers insights into their removal from one university's experience.

PMID- 16096149
TI  - Models of interprofessional learning in Canada.
AB  - This article provides an overview of interprofessional education in Canada, with
      a view to defining programs at all levels in terms of what models have been
      employed. The available information implies that the lack of convincing evidence
      of the effectiveness of existing programs is probably the most serious problem
      for the expansion of interprofessional education. The objectives of the programs
      are both to increase the knowledge about the other professions and their scope of
      practice, and to improve team function, and there are a number of well
      established interprofessional programs in Canada that are designed to achieve
      these objectives, and many other examples of programs that are partial or
      planned. Despite this, the present interprofessional education initiatives tend
      to involve only a small proportion of the total health work trainees. There is a
      need for programs that are more widespread. The most frequent model involves a
      mandatory experience, which is case-based, involves all the students registered
      in Health Faculties, and where the students form interprofessional student teams.
      In addition to examining believable cases, the students also learn some specific
      information about interacting with the other professions and gain knowledge about
      the roles, knowledge and contributions that can be made by professions other than
      their own.

PMID- 16096150
TI  - The conceptual basis for interprofessional collaboration: core concepts and
      theoretical frameworks.
AB  - Interprofessional collaboration is a key factor in initiatives designed to
      increase the effectiveness of health services currently offered to the public. It
      is important that the concept of collaboration be well understood, because
      although the increasingly complex health problems faced by health professionals
      are creating more interdependencies among them, we still have limited knowledge
      of the complexity of interprofessional relationships. The goal of this literature
      review was to identify conceptual frameworks that could improve our understanding
      of this important aspect of health organizations. To this end, we have identified
      and taken into consideration: (A) the various definitions proposed in the
      literature and the various concepts associated with collaboration, and (B) the
      various theoretical frameworks of collaboration. Our results demonstrate that:
      (1) the concept of collaboration is commonly defined through five underlying
      concepts: sharing, partnership, power, interdependency and process; (2) the most
      complete models of collaboration seem to be those based on a strong theoretical
      background, either in organizational theory or in organizational sociology and on
      empirical data; (3) there is a significant amount of diversity in the way the
      various authors conceptualized collaboration and in the factors influencing
      collaboration; (4) these frameworks do not establish clear links between the
      elements in the models and the outputs; and (5) the literature does not provide a
      serious attempt to determine how patients could be integrated into the health
      care team, despite the fact that patients are recognized as the ultimate
      justification for providing collaborative care.

PMID- 16096151
TI  - The determinants of successful collaboration: a review of theoretical and
      empirical studies.
AB  - Successful collaboration in health care teams can be attributed to numerous
      elements, including processes at work in interpersonal relationships within the
      team (the interactional determinants), conditions within the organization (the
      organizational determinants), and the organization's environment (the systemic
      determinants). Through a review of the literature, this article presents a
      tabulated compilation of each of these determinant types as identified by
      empirical research and identifies the main characteristics of these determinants
      according to the conceptual work. We then present a "showcase" of recent Canadian
      policy initiatives--The Canadian Health Transition Fund (HTF)--to illustrate how
      the various categories of determinants can be mobilized. The literature review
      reveals that very little of the empirical work has dealt with determinants of
      interprofessional collaboration in health, particularly its organizational and
      systemic determinants. Furthermore, our overview of experience at the Canadian
      HTF suggests that a systemic approach should be adopted in evaluative research on
      the determinants of effective collaborative practice.

PMID- 16096152
TI  - Effectiveness of pre-licensure interprofessional education and post-licensure
      collaborative interventions.
AB  - In this paper we scanned and summarized the empirical research evidence and found
      that the effects of pre-licensure interprofessional education on patient/client
      care are unknown. In contrast, for post-licensure collaboration interventions,
      there is a growing body of evidence suggesting positive effects on the delivery
      of care. The coverage of this latter evidence, however, is patchy, being
      especially weak in primary care. In interprofessional education, where policy
      level interventions have been value driven for the last half century, we have
      identified a base of evidence for the effectiveness of certain post-licensure
      collaboration interventions; this evidence is lacking for pre-licensure
      interprofessional education. If interventions and policies for both pre-licensure
      interprofessional education and post-licensure collaboration are implemented
      without accompanying rigorous evaluation research, we will remain mired in this
      same uncertainty into the future.

PMID- 16096153
TI  - Factors in implementing interprofessional education and collaborative practice
      initiatives: findings from key informant interviews.
AB  - Health Canada (the federal government department in Canada responsible for health
      issues) commissioned a research team to conduct an environmental scan and
      research report in order to understand interprofessional education and
      collaborative patient-centred practice (IECPCP). This paper presents the findings
      from semi-structured telephone interviews with key informants conducted as part
      of the environmental scan. Grounded theory analysis was employed in order to
      identify factors associated with interprofessional education and collaborative
      practice initiatives. These factors were grouped according the following themes:
      lack of consensus regarding terminology; the need for both champions and external
      support; sensitization to the effects of professional culture, and logistics of
      implementation. Findings are discussed related to the literature and to the other
      papers included in this supplement to the Journal of Interprofessional Care.

PMID- 16096154
TI  - New approaches to interprofessional education and collaborative practice: lessons
      from the organizational change literature.
AB  - This paper highlights a variety of issues from the organizational change
      literature that are especially relevant to the implementation of initiatives in
      interprofessional education (IPE) for collaborative practice (CP). At the level
      of the individual, these include the existence of strong professional cultures
      and the need to motivate change. At the level of the organization, context and
      leadership for IPE and CP are relevant. At the system level, a discussion of
      incremental versus radical forces for change is particularly germane. Drawing on
      relevant theoretical and empirical literature, we address each of these three
      domains and highlight lessons learned from the study of organizational change to
      the implementation and adoption of IPE and CP. The paper concludes with a set of
      key recommendations suggested for reducing the incidence of implementation
      failure.

PMID- 16096155
TI  - Interprofessional teamwork: professional cultures as barriers.
AB  - Each health care profession has a different culture which includes values,
      beliefs, attitudes, customs and behaviours. Professional cultures evolved as the
      different professions developed, reflecting historic factors, as well as social
      class and gender issues. Educational experiences and the socialization process
      that occur during the training of each health professional reinforce the common
      values, problem-solving approaches and language/jargon of each profession.
      Increasing specialization has lead to even further immersion of the learners into
      the knowledge and culture of their own professional group. These professional
      cultures contribute to the challenges of effective interprofessional teamwork.
      Insight into the educational, systemic and personal factors which contribute to
      the culture of the professions can help guide the development of innovative
      educational methodologies to improve interprofessional collaborative practice.

PMID- 16096156
TI  - Regulatory and medico-legal barriers to interprofessional practice.
AB  - Unlike the other contributions to this issue, this paper is concerned with the
      prospects and potential ramifications of implementing interprofessional practice
      from the legal standpoint. The authors focus on the two forums where the major
      legal issues are likely to be played out: the laws under which health care
      professionals are regulated; and the law of professional malpractice as applied
      by the courts under the tort of negligence. The goal is to examine the regulatory
      and medico-legal barriers that might prevent or inhibit health care professionals
      from working together on an interprofessional basis, and to forecast the kinds of
      changes within legal systems which will be necessary to accommodate the change.
      The first part of the paper focuses on the legal regimes which govern the
      Canadian health care system, and argues that the essential integrity of the
      system of professional self-regulation must be protected in programs of reform
      that seek to create space for interprofessional practice. The authors also
      propose a number of specific initiatives of review and legislative change as
      examples of the role that legal reform can play in the shift to a culture of
      interprofessional regulation. The second part of the paper focuses on malpractice
      law and suggests that, while in the long term the superior quality of care
      brought about by interprofessional practice should produce less liability, in the
      short term interprofessional practice may fit uneasily within the legal
      constructs traditionally employed by the courts to evaluate malpractice claims.
      The authors propose three strategies designed to minimize this risk.

PMID- 16096157
TI  - Cultural considerations in interprofessional education and practice.
AB  - Promoting cultural competency in health care was examined from the Canadian
      perspective, and explored practice environments and educational programs for
      future health professionals that foster cultural awareness and support culturally
      sensitive care. Many of the issues raised are generic and likely to occur
      whenever patients' health practices and beliefs differ from conventional Western
      care. The main theme that emerged with respect to the practice environment was
      the use of a participatory action approach to foster collaboration with patients,
      traditional healers and the community. Successful collaboration is likely to
      result in a blend of ideas and perspectives from traditional health practices and
      conventional Western health care. With respect to education, programs need to
      focus on providing opportunities both in the classroom and in the clinical arena
      for students to work in interprofessional teams. These teams should not only
      comprise partners from medicine, nursing, physical therapy and other health
      professions but also include aboriginal paraprofessionals. Pedagogical
      initiatives also need to incorporate case-based formats and interactive sessions
      with patients and families. The principles underlying this approach: openness,
      mutual respect, inclusiveness, responsiveness and understanding one's roles
      should be fundamental to the delivery of culturally competent health care to all
      ethnic communities.

PMID- 16096159
TI  - Investigation, treatment and monitoring of late-onset hypogonadism in males.

PMID- 16096160
TI  - ISA, ISSAM and EAU recommendations for the investigation, treatment and
      monitoring of late-onset hypogonadism in males: scientific background and
      rationale.
AB  - Prescription sales for testosterone products have substantially increased over
      the last several years reflecting the growing awareness of physicians for the
      potential benefits of testosterone replacement therapy in men with hypogonadism.
      Indiscriminate administration of testosterone poses a risk and has to be
      deprecated. Testosterone supplementation to treat late-onset hypogonadism (LOH),
      a term for androgen deficiency in elderly men, is still controversially discussed
      mainly due to a lack of large, controlled clinical trials on efficacy and safety.
      To provide guidance for physicians primarily dealing with aging men, ISSAM is
      periodically updating and publishing its recommendations as new data become
      available [Morales A, Lunenfeld B. International Society for the Study of the
      Aging Male. Investigation, treatment and monitoring of late-onset hypogonadism in
      males. Official recommendations of ISSAM. International Society for the Study of
      the Aging Male. Aging Male 2002;5:74-86 and Morales A, Lunenfeld B. Androgen
      replacement therapy in aging men with secondary hypogonadism. Draft
      recommendations for endorsement by ISSAM. Aging Male 2001;4:1]. Following a panel
      discussion at the 4th ISSAM Congress in Prague in February 2004, the
      International Society of Andrology (ISA), the International Society for the Study
      of the Aging Male (ISSAM) and the European Association of Urology (EAU) revised
      existing recommendations on the definition, diagnosis and management of LOH. The
      recommendations are based on the currently available scientific data on androgen
      supplementation therapy and should be regarded as provisional until larger-scale,
      long-term studies are available. While certainly not intending to be exhaustive,
      this review will highlight some relevant background information and provide the
      underlying scientific rationale for the ISA, ISSAM and EAU recommendations on LOH
      published in this issue.

PMID- 16096161
TI  - Biochemical markers of bone metabolism in healthy elderly men. The relationship
      to physical activity.
AB  - The purpose of the present study was to examine the serum levels of bone turnover
      markers and interleukin 1beta in healthy elderly men with different levels of
      habitual physical activity. The study was conducted on 40 healthy men aged
      between 65 and 85 years (mean 74.0 +/- 7.55 years). The study population was
      divided into two groups with respect to the level of physical activity: 22 less
      active subjects (energy expenditure related to physical activity below 1600 kcal
      per week) and 18 more active subjects (above 1600 kcal per week). To estimate the
      physical activity of the study population, weekly energy expenditure was measured
      in each subject with use of Caltrac accelerometer. In the blood serum levels of
      bone formation marker--osteocalcin and resorption marker--the C-terminal
      telopeptide of collagen I (ICTP), and interleukin-1beta were determined.
      Concentrations of osteocalcin and ICTP in less active subjects were significantly
      higher (by 3.62 ng/ml and by 1.21 mug/l respectively, p < 0.05), reflecting the
      higher bone turnover in comparison to values determined in more active subjects.
      Positive correlations between ICTP and osteocalcin levels (r = 0.5814 and r =
      0.6526; p < 0.05), and between ICTP and IL-1beta (r = 0.5823 and r = 0.6040; p <
      0.05) in less and more active men were found. On the ground of the presented
      study it can be concluded that the decreased bone turnover occurred in men with
      higher level of habitual physical activity. This study showed the relationship
      between serum level of IL-1beta and bone resorption but the habitual physical
      activity has no effect on this cytokine activity.

PMID- 16096162
TI  - Perceptions and attitudes towards aging in two culturally diverse groups of aged
      males: a South African experience.
AB  - The role of men has undergone tremendous change over the last decade due to
      various reasons. The researcher tried to combine two objectives in this study.
      Firstly the focus was on perceptions and attitudes of aged males towards
      themselves, significant others and the general process of aging. The second
      objective was to determine the culturally diverse perceptions and attitudes of
      aged males towards aging and some concomitant factors. The study was done within
      the qualitative paradigm. Seeing that research of this nature has seldom been
      undertaken, an exploratory research design was embarked on. Two culturally
      different groups, the one consisting of 12 aged black men and the other
      consisting of 12 aged white men, were established. Members for the two groups
      were selected by way of the accidental sampling technique. Vast differences were
      found between the two groups on some aspects, while on other aspects there were
      little differences.

PMID- 16096163
TI  - Aging in Asia: a cultural, socio-economical and historical perspective.
AB  - Asia has about 60% of the world population and population aging is occurring more
      rapidly in Asia than in Western countries. The group aged 65 years and above will
      increase from 207 million in 2000 to 857 million in 2050, a staggering increase
      of 314%. The diversity in economic, demographic, religious, cultural and geo
      political factors in Asia is unparalleled by any other continent, and is, in
      part, contributory to the rapid rise in population aging. By 2050, those under 15
      years old will have shrunk from 30% in 2000 to 19%, while those aged 65 years and
      above will increase from 6% to 18%. In addition, the gender divide still persists
      with 100 elderly women to 70 elderly men. These projected demographic changes
      pose three major challenges: 1) how best to address the rising population of the
      group aged 65 years and above, 2) how to address the shrinking population of the
      young as well as the working adults, and 3) how to address the problems arising
      from the disproportionate increase in older women than men. From now to 2050, it
      will be expeditious for each country in Asia to look into ways of reversing the
      decline in total fertility rates (TFRs) and restore to replacement levels. If
      not, at least introduce measures to halt its free fall. Due to the complexity of
      factors that have influenced the fall in TFRs in Asia, it will be a daunting task
      to reverse this fall. There is no "single size fits all" solution to this complex
      problem. Research work in this short-term strategy in addressing the aging
      population is urgent. In the longer term, the East-West Centre have suggested
      four modalities, 1) establish policies and programmes that enhance traditional
      Asian systems of family support for the elderly; 2) introduce policy reform that
      encourages the elderly who are still capable of remaining in the work force; 3)
      create institutions and systems that support high levels of personal saving; and
      4) formulate public programmes, including pension schemes and national healthcare
      systems. We need to work while there is time.

PMID- 16096165
TI  - Prevention of osteoporosis is still a valid aim for hormone therapy.

PMID- 16096166
TI  - Postmenopausal osteoporosis: therapeutic options.

PMID- 16096167
TI  - Estrogens and the skin.
AB  - OBJECTIVE: A review of the medical literature concerning the effect of the
      menopause and its hormonal treatment on the skin. METHODS: An extensive Medline
      and Pubmed internet search utilizing the key words: collagen, elastin, estrogen,
      hormone replacement therapy, skin and aging. RESULTS: The literature review
      demonstrated a wide array of research ranging from basic science work to clinical
      implications of the effects of the menopause and its treatment on the skin.
      CONCLUSION: Estrogen loss at menopause has a profound influence on skin. Estrogen
      treatment in postmenopausal women has been repeatedly shown to increase collagen
      content, dermal thickness and elasticity, and data on the effect of estrogen on
      skin water content are also promising. Further, physiologic studies on estrogen
      and wound healing suggest that hormone replacement therapy (HRT) may play a
      beneficial role in cutaneous injury repair. Results on the effect of HRT on other
      physiologic characteristics of skin, such as elastin content, sebaceous
      secretions, wrinkling and blood flow, are discordant. Given the responsiveness of
      skin to estrogen, the effects of HRT on aging skin require further examination,
      and careful molecular studies will likely clarify estrogen's effects at the
      cellular level.

PMID- 16096168
TI  - Testosterone in older men after the Institute of Medicine Report: where do we go
      from here?
AB  - Despite nearly a half-century of research on aging and sex steroids in men,
      answers to key questions that would allow us to confidently assess risk:benefit
      ratios for androgen replacement in older men with the partial androgen deficiency
      of aging men (PADAM) syndrome remain uncertain. Although it is now reasonably
      clear that a significant percentage of otherwise healthy older men have decreases
      in testosterone and bioavailable testosterone to levels consistent with
      hypogonadism, the clinical implications of this change remain uncertain. Data
      suggest that low testosterone in older men is correlated to varying degrees with
      loss of lean body mass and muscle strength, and increased total and central body
      fat. Less certain, but suggestive, are data relating low testosterone levels to
      decreased bone density, loss of insulin sensitivity, and cognitive and affective
      deterioration, as well as reduced sexual function. Replacement of testosterone in
      older men has shown some positive effects on each of these variables, but
      findings have been inconsistent, perhaps because studies have employed different
      preparations and doses of androgens, treated for various durations, and defined
      their target populations in different ways. As important as beneficial effects is
      the potential for adverse effects, which may be greater in older men. Possible
      problems include sleep apnea, erythrocytosis, dyslipidemia with acceleration of
      atherosclerosis, and, of greatest concern, prostate cancer or hyperplasia.
      Studies to date have suggested that these outcomes are not major risks, but, in
      the absence of a large, randomized trial or trials, definitive information is not
      available. The US National Academies Institute of Medicine's recent report
      recommends that the National Institutes of Health support small efficacy trials
      aimed at treatment of androgen deficiency-related clinical conditions, but not a
      large, randomized trial to elucidate risk:benefit ratios. This recommendation, if
      adhered to, is likely to delay, rather than foster, progress in this important
      area.

PMID- 16096169
TI  - Nomegestrol acetate may enhance the skeletal effects of estradiol on biochemical
      markers of bone turnover in menopausal women after a 12-week treatment period.
AB  - OBJECTIVE: To compare the effects of a 12-week treatment with 17ss-estradiol
      given alone and in sequential combination with 3.75 mg of nomegestrol acetate
      (Naemis), or a placebo on biochemical markers of bone turnover in menopausal
      women. PATIENTS AND METHODS: A double-blind, randomized, placebo and estradiol
      controlled multicenter study was conducted. A total of 176 patients who had been
      menopausal for 1-10 years, hysterectomized or not, having no contraindications to
      hormone replacement therapy, without any risks factors for osteoporosis, received
      one of these treatments during 12 weeks: placebo, 1.5 mg estradiol (E(2)) or 1.5
      mg E(2)/3.75 mg nomegestrol acetate (E(2)/NOMAC). The primary efficacy variables
      were the change in bone markers (total alkaline phosphatase, bone alkaline
      phosphatase and osteocalcin; urinary type-I collagen peptides). RESULTS: The four
      biochemical markers decreased only in the E(2)/NOMAC group. Bone alkaline
      phosphatase, osteocalcin and urinary type-I collagen peptides decreased in the
      E(2) group. For both active treatment groups compared to the placebo group, the
      changes were statistically significant after a 12-week treatment. There were no
      statistically significant differences between the E(2) and the E(2)/NOMAC groups
      except for total serum alkaline phosphatase, whose mean value decreased in the
      E(2)/NOMAC group but increased slightly in the E(2) group (p < 0.001).
      Furthermore, after a 6-week treatment, the changes in biochemical markers of bone
      turnover were similar to those found after 12 weeks. Safety data were
      satisfactory with regard to estradiol given alone or in combination with
      nomegestrol acetate. CONCLUSION: These results demonstrated that 1.5 mg E(2) is
      effective in reducing bone turnover in postmenopausal women and proved that the
      combination of 1.5 mg E(2) and 3.75 mg nomegestrol acetate has no deleterious
      effect on bone remodelling.

PMID- 16096170
TI  - Quality-of-life assessment in community-dwelling, middle-aged, healthy women in
      Japan.
AB  - OBJECTIVES: To determine the quality of life (QOL) of middle-aged Japanese
      healthy women during the menopausal transition, to identify the correlation
      between decreasing quality of life and the severity of menopausal symptoms in
      those women, and to evaluate the number of women who sought treatment/health-care
      support and their expectations for health-care services. METHODS: This was a
      community-based study, performed in collaboration with the Munakata Women's
      Midlife Health Project. The participants attended an annual medical check-up and
      cancer screenings, and led an everyday life without receiving medical treatment.
      Their quality of life was assessed with the World Health Organization QOL
      assessment (WHOQOL) and the severity of menopausal symptoms was assessed with the
      Kupperman index. Their expectations for health-care services were determined with
      an open-ended questionnaire. RESULTS: The mean scores of the Kupperman index in
      the peri- and postmenopausal states were significantly higher than that in the
      premenopausal states, whereas there was no significant difference of quality of
      life scored by the WHOQOL in the three groups. In spite of recruiting healthy
      middle-aged women, 24.4% of the perimenopausal and 26.6% of the postmenopausal
      women suffered from moderate or severe menopausal symptoms. The decreasing level
      of quality of life was correlated with the severity of the menopausal symptoms in
      the peri- and postmenopausal women. The participants did not receive medical
      support except in two cases, but 83.0% of them wished to participate in a seminar
      concerning menopause. Several of them sought treatment, health-care support and
      advice on how to maintain their health during and after the menopausal
      transition. CONCLUSIONS: Nearly one-quarter of Japanese community-dwelling,
      healthy women in the peri- and postmenopausal states suffered from menopausal
      symptoms, which decreased their quality of life in everyday life.

PMID- 16096171
TI  - UK women doctors' use of hormone replacement therapy: 10-year follow up.
AB  - OBJECTIVES: To determine changes in the prevalence and duration of use of hormone
      replacement therapy (HRT) by women doctors over 10 years. METHODS: Questionnaire
      survey of 1234 UK women doctors (randomized, stratified sample), compared with a
      similar survey in 1993. RESULTS: In women aged 50-64 years, the age-standardized
      prevalence of ever-use of HRT had increased from 53.4% in 1993 to 66.2% in 2003
      (p<0.001). There was a marked reduction in uptake by women under 50 years, while
      the age-standardized prevalence of current use in women aged 50-64 years was
      unchanged at 38.1%. The discontinuation rate in this age group had increased from
      27.8% to 42.4% (p<0.001). Over 20% of women aged 65-74 years were still using
      HRT. The median duration of HRT use was 8.1 years by current users and 5 years by
      past users. The major indications were symptom relief and osteoporosis
      prevention. Current users of HRT tended to have more definite views about the
      potential risks and benefits of long-term use than past or never-users.
      CONCLUSIONS: The proportion of women doctors starting HRT increased after 1993,
      but uptake and continuation rates have now both declined, consistent with
      prescription data, probably reflecting the changing nature of the evidence base.
      However, many women doctors still intended to continue long-term HRT.

PMID- 16096172
TI  - Femal, a herbal remedy made from pollen extracts, reduces hot flushes and
      improves quality of life in menopausal women: a randomized, placebo-controlled,
      parallel study.
AB  - BACKGROUND: The fact that hormone replacement therapy has been claimed to
      increase the risk of breast cancer has made it relevant to search for new non
      hormonal treatments of menopausal symptoms. OBJECTIVES: This study aimed to
      evaluate whether Femal, a herbal remedy made from pollen extracts, alleviates the
      symptoms of the menopause, especially hot flushes. DESIGN: A randomized, double
      blind, placebo-controlled, parallel trial of 64 menopausal women, of whom 54
      completed the trial. After an initial run-in phase of 1 month, the women were
      randomly given either two Femal tablets each morning, or two identical placebo
      tablets, for 3 months of treatment. On inclusion, and then at 4-week intervals,
      the patients were asked to evaluate 16 symptoms of the menopause using Menopause
      Rating Scales (MRS). In addition, every day throughout the study, certain
      menopausal symptoms were recorded in a diary. RESULTS: The two treatment groups
      were identical regarding demographic data and the initial symptom scores. In the
      active-treatment group, 65% responded with a reduction in hot flushes compared
      with 38% in the placebo group (p<0.006) and, in this group, the number of hot
      flushes registered in diaries declined after 3 months by 27% as compared to the
      placebo group (p<0.026). MRS evaluation of hot flushes yielded similar results
      (p<0.031). There were 23% and 22% decreases in hot flushes after 2 and 3 months
      of treatment, respectively, and after both intervals of time the inter-group
      comparisons were significantly affected. An overall evaluation of the trend in 15
      other 'quality-of-life' parameters showed likewise in favor of the pollen extract
      (p<0.031). CONCLUSION: The pollen extract Femal significantly reduces hot flushes
      and certain other menopausal symptoms when compared to placebo.

PMID- 16096173
TI  - Hormone replacement therapy and WONCA/COOP functional status: a cross-sectional
      population-based study of women in Israel.
AB  - BACKGROUND: Current indications for hormone replacement therapy (HRT) for
      menopausal women include symptom relief, but recent studies have raised concerns
      about the safety of HRT. Little data are available on the effect of HRT on
      functional status of women taking hormonal preparations after menopause.
      OBJECTIVE: To assess the association between hormonal replacement therapy and
      functional status in menopausal women. METHODS: A cross-sectional survey,
      population-based study of 682 menopausal women between the ages of 50 and 70
      years registered with six family physicians in central Israel. The main outcome
      measure was the functional status measured by the WONCA/COOP charts. RESULTS: A
      total of 587 women (86%) completed questionnaires. Univariate analysis showed an
      association between current use of HRT and improved functional status. However
      this association was diminished in a regression analysis which controlled for
      sociodemographic status and health variables. The contribution of HRT to
      functional status was small but was found to be significant in the domains of
      general health status (1.9%, p<0.002), sleep (0.9%, p<0.044), physical activities
      (2.1%, p<0.001) and feelings (1.0%, p<0.033). The contribution of HRT to daily
      activities, social activities, change in health status and pain was not
      significant. CONCLUSIONS: HRT use had a small contribution to improved functional
      status in half of the domains measured by the WONCA/COOP charts.

PMID- 16096174
TI  - Profile of menopausal women in rural north India.
AB  - OBJECTIVE: To ascertain the profile of menopausal women in rural north India.
      Setting Six villages were selected in a rural field practice area of Department
      of Community Medicine, Postgraduate Institute of Medical Education and Research,
      Chandigarh, north India. METHODS: A female social worker obtained relevant data
      in the study area during 1999-2001. This involved individual interviews of women
      aged 35-55 years through a house-to-house survey. RESULTS: Of the 558 enlisted
      women, 152 (27.2%) had attained menopause. Average age at menopause was 44.1
      years. More than half (53%) reported seven or more symptoms at menopause.
      Diminished vision was reported as the most common symptom at menopause. The
      majority (85%) admitted that menopause adversely affected women's physical
      health. However, most of them (95%) considered menopause socially good for women
      and welcomed it. None of our respondents reported use of hormone replacement
      therapy. CONCLUSION: Women in rural north India viewed menopause positively.
      Medication of menopause was minimal.

PMID- 16096175
TI  - Hormone replacement therapy and breast density changes.
AB  - OBJECTIVES: To compare the incidence of increased breast density and tenderness
      in postmenopausal women associated with transdermal (Estalis/Combipatch),
      Novartis, Basel, Switzerland) and oral (Kliogest), Schering AG, Berlin, Germany)
      hormone replacement therapy (HRT). METHODS: A total of 202 postmenopausal women
      were randomized to transdermal or oral HRT. Mammograms obtained at study entry
      and after 1 year of treatment were assessed for percent breast density by means
      of the digital segmentation and thresholding technique. Breast tenderness was
      assessed at each study visit. RESULTS: The mean breast density by ANCOVA after
      adjusting for screening value at study end was significantly lower for women
      using Estalis (38.4%, standard error 0.9%) compared with Kliogest (46.9%,
      standard error 1.5%) (p<0.0001). Significantly fewer women using transdermal HRT
      had an increase in mammographic breast density or breast tenderness compared to
      oral HRT. Of the women using transdermal HRT, 39.1% had no change in breast
      density compared to 15.7% for women using oral HRT. Only 4% of women using
      transdermal HRT had a marked increase in density (>25%) compared to 15.7% of
      women using oral HRT. Overall, 36.0% of patients in the transdermal group
      reported breast tenderness at some point during the 1-year study, compared with
      57.6% in the oral HRT group (p=0.0002). CONCLUSION: Transdermal HRT use is
      associated with a significantly lower incidence of increased mammographic breast
      density and breast tenderness compared with oral HRT.

PMID- 16096176
TI  - Effect of a gonadotropin releasing hormone analog on cerebral hemodynamics in
      premenopausal women.
AB  - BACKGROUND: Impaired reactivity of cerebral blood vessels is associated with
      increased risk of stroke. Female sex hormones have vasoactive effects in a number
      of vascular beds but their effects upon the cerebral circulation are not well
      understood. Ultrasound techniques allow us to examine the ability of intracranial
      vessels to dilate in response to a pharmacological stimulus (the carbonic
      anhydrase inhibitor acetazolamide). We studied intracranial hemodynamics in a
      group of premenopausal women before and after induction of a temporary
      hypoestrogenic state. METHODS: We examined middle cerebral artery mean flow
      velocity, common and internal carotid artery pulsatility index and
      cerebrovascular reactivity to acetazolamide (CVR) in a group of women undergoing
      treatment for menstrual disorders. Volunteers underwent ultrasound examination
      during the follicular phase of the menstrual cycle and after completing treatment
      with gonadotropin releasing hormone (GnRH, goserelin 3.6 mg) administered
      subcutaneously every 28 days for 12 weeks. The study was conducted in a
      prospective, single-blind fashion and analyzed using parametric comparisons of
      means to examine change in intracranial hemodynamic parameters between pre- and
      postmenopausal states. RESULTS: Twelve premenopausal women aged 37.2+/-7 years
      and without overt vascular disease completed the protocol. GnRH reduced serum
      estrogen concentration (215.6+/-122 pg/ml vs. 82.4+/-12 pg/ml, p=0.0047) but this
      was not associated with a change in CVR (145+/-19% and 146+/-14% for follicular
      and post-GnRH studies, respectively (p=0.6). No significant changes in blood
      pressure, internal carotid or middle cerebral artery pulsatility or mean flow
      velocity were observed between time points. CONCLUSION: Neither resting cerebral
      hemodynamics nor reactivity of cerebral resistance vessels to a potent
      vasodilatory stimulus changed when the circulating concentration of estradiol was
      artificially decreased using a GnRH agonist. Induction of a hypoestrogenic state
      does not appear to influence cerebral vasodilatory capacity in the short term.

PMID- 16096177
TI  - Uncertainty with unregulated products.

PMID- 16096178
TI  - Oral ivermectin for the treatment and prophylaxis of scabies in prison.
AB  - INTRODUCTION: Oral ivermectin has been widely used to treat various human
      diseases, such as filariasis, myiasis, larva migrans, strongyloidiasis and
      scabies (both the common and crusted forms). However, there are only a small
      number of papers on the effects of this drug for the control of scabies in
      infested environments. The current study shows the results obtained with the
      collective treatment of inmates of a public jail. MATERIALS AND METHODS: A total
      of 123 inmates living in a restricted and contaminated environment were evaluated
      clinically by experienced dermatologists for the assessment of the degree of
      infestation by Sarcoptes scabiei, and were then treated with oral ivermectin (200
      300 micorg/kg single dose repeated after 7 days). Both clothing and environment
      were disinfected. Patients were re-evaluated after 15 days. RESULTS: In all, 78%
      of the inmates were infected upon initial evaluation. Re-evaluation 15 days after
      repeat treatment revealed a cure rate of 91.05%. Prophylaxis was also highly
      effective, where 93.2% of the non-infected inmates and virtually all the house
      staff remained disease-free throughout the study period. Two of the 29 inmates
      (6.8%) who showed no apparent lesions upon initial examination were found to be
      infected upon re-evaluation. These patients responded well to a third dose of
      ivermectin. CONCLUSIONS: Oral ivermectin at a dose of 300 microg/kg single dose
      repeated after 7 days proved effective for the treatment and prophylaxis of
      scabies in an infected institutional environment.

PMID- 16096179
TI  - A randomized study of the safety, absorption and efficacy of pimecrolimus cream
      1% applied twice or four times daily in patients with atopic dermatitis.
AB  - BACKGROUND: Pimecrolimus cream 1% (Elidel), a non-steroid inhibitor of
      inflammatory cytokines, is effective in the treatment of atopic dermatitis,
      without corticosteroid-related side effects such as skin atrophy. It is indicated
      for twice-daily application. More frequent applications might be expected either
      to enhance efficacy or increase toxicity. This study compared the safety,
      efficacy and systemic absorption of pimecrolimus administered twice daily
      (recommended dose) and four times daily early in the treatment of patients with
      moderate to severe atopic dermatitis. METHODS: Adolescent and adult patients with
      moderate to severe atopic dermatitis were randomly assigned to a twice daily
      (BID) treatment group (n = 24) or a four times daily (QID) group (n = 25). During
      days 1-7, patients in the QID group applied pimecrolimus four times daily, and
      patients in the BID group applied pimecrolimus twice daily plus vehicle
      equivalent twice daily. During days 8-21, all patients were required to use
      pimecrolimus twice daily and had the option to use up to two further daily
      treatments (pimecrolimus in the QID group and vehicle equivalent in the BID
      group). Blood sampling occurred 2, 4, and 6 hours after the first morning
      application on days 1 and 5 and then prior to the first morning application on
      days 8 and 15, and any time on day 22. RESULTS: Only 3 (12%) QID patients and 4
      (17%) BID patients reported adverse events (primarily mild, transient application
      site burning) with no significant difference between treatment groups in the
      frequency, type, or severity of adverse events. The median daily number of
      applications in the QID group during days 8-21 when two additional doses were
      optional remained at four. Pimecrolimus blood levels from a subgroup of 22
      patients showed no difference in systemic exposure between the two dosing
      regimens. All but three (one in the QID group, two in the BID group) patients had
      blood levels below the limit of quantification; the highest single blood level of
      pimecrolimus measured in any patient was 1.37 ng/ml (QID group). Both the QID and
      BID regimens improved the signs and symptoms of atopic dermatitis similarly as
      measured by improvements in pruritus severity score, Investigator's Global
      Assessment, Eczema Area and Severity Index, percentage of body surface area
      affected, and patient's self-assessment of disease control. CONCLUSIONS: The data
      suggest that increasing pimecrolimus application from twice daily to four times
      daily to treat moderate to severe atopic dermatitis for up to 3 weeks does not
      alter the safety profile nor does it increase the efficacy of treatment. Systemic
      absorption of pimecrolimus applied BID and QID is minimal and is not different
      between dosing regimens. Patients and physicians familiar with the potential
      hazards of overuse of topical corticosteroids should be reassured that if
      pimecrolimus is applied at twice the recommended BID dose for short periods of
      time, there is no effect on safety, tolerability, or systemic absorption.

PMID- 16096180
TI  - Non-melanoma skin cancer in patients with atopic dermatitis treated with topical
      tacrolimus.
AB  - OBJECTIVE: To determine whether atopic dermatitis (AD) patients treated with
      tacrolimus ointment experienced an increased risk of non-melanoma skin cancer
      (NMSC). METHODS: Data were collected from 9813 adult and paediatric patients with
      AD who applied 0.03% or 0.1% tacrolimus ointment twice daily and were examined
      every 3 months during the tacrolimus ointment development programme. RESULTS:
      Thirteen adult patients were diagnosed with NMSC during the follow-up period. All
      patients with NMSC were white adults and 12 were over 40 years of age. Based on
      1718 patient-years of tacrolimus ointment exposure in patients 40 years of age,
      the calculated incidence of NMSC did not suggest an increased risk of first NMSC
      over that of a similarly aged US cohort. CONCLUSION: This study does not indicate
      an increased risk for the development of NMSC in patients with AD treated with
      tacrolimus ointment for a mean duration of 208 days with a maximum observation
      period of 1479 days.

PMID- 16096181
TI  - A survey of traditional Chinese medicine use in children with atopic dermatitis
      attending a paediatric dermatology clinic.
AB  - Use of traditional Chinese medicine (TCM) for various paediatric diseases has
      been popular. Often, parents or caregivers believe that herbs possess therapeutic
      effects without any harmful consequence. This fallacy is especially prevalent in
      the caregivers of children with chronic diseases such as atopic dermatitis (AD).
      We interviewed 227 consecutive children with AD to assess the attitudes of the
      caregivers to TCM use, based on a 14-item questionnaire. Of these respondents, 67
      (30%) admitted that the child had been given TCM in the past 12 months, one-third
      of these were currently taking TCM and one-quarter had used TCM for 6 months or
      more. TCM was prescribed by a Chinese medicine practitioner in 63 patients (94%),
      and herbal tea/soup was the commonest TCM taken. The majority (94%) had not been
      told of any possible side effects of TCM. Nearly 60% thought that TCM helped to
      improve their child's AD. Respondents for children with severe eczema were less
      likely to think that TCM helped to improve their child's eczema than those with
      mild or moderate eczema. TCM use was not associated with parental ages or
      'grandparent as caregiver' but 'severe AD' was an independent factor for TCM use
      (OR 3.24, 95% CI 1.67-6.31; p = 0.0003).

PMID- 16096182
TI  - Clobetasol propionate lotion, an efficient and safe alternative to clobetasol
      propionate emollient cream in subjects with moderate to severe plaque-type
      psoriasis.
AB  - BACKGROUND: Various formulations of clobetasol propionate are currently used to
      treat psoriasis due to its anti-inflammatory, anti-pruritic, vasoconstrictive and
      immunomodulating properties. OBJECTIVE: To assess the efficacy, safety and
      remission profile of clobetasol propionate lotion compared to that of clobetasol
      propionate emollient cream and lotion vehicle in subjects with moderate to severe
      plaque-type psoriasis. METHODS: Multicentre, investigator-blind, randomized,
      active- and vehicle-controlled, parallel-group study. RESULTS: A total of 192
      subjects were treated: 82 with clobetasol propionate lotion, 81 with clobetasol
      propionate cream and 29 with the vehicle. Clobetasol propionate lotion was
      significantly more effective than vehicle lotion and was comparable in efficacy
      to the emollient cream after 4 weeks of treatment. Treatment success was higher
      for subjects in the clobetasol propionate lotion group than in the emollient
      cream group after 4 weeks of a treatment-free follow-up period. Clobetasol
      propionate lotion was safe and well tolerated. CONCLUSION: The present study
      demonstrates that clobetasol propionate lotion is an efficacious, safe and well
      tolerated alternative to the currently available emollient cream formulation,
      while showing a better remission profile after 4 weeks of treatment-free follow
      up period.

PMID- 16096183
TI  - Treatment of localized persistent plaque psoriasis with incoherent narrowband
      ultraviolet B phototherapy.
AB  - PURPOSE: This study evaluated the efficacy of targeted UVB phototherapy treatment
      of chronic persistent psoratic plaques with localized incoherent UVB
      phototherapy. METHODS: Sixteen subjects were enrolled. The final group was
      composed of eight men and seven women, each having one to seven chronic, stable
      psoriatic plaques. Each plaque was treated with fluences ranging from 3 to 7 MED
      using a fibre-coupled incoherent phototherapy device twice weekly for a maximum
      of 13 sessions. Assessments with a combination of three scores, each on a scale
      from 0 to 4, for scaling, erythema and induration (SEI score) were performed.
      RESULTS: The patients received from 6 to 13 sessions (mean 9.6). The SEI score
      decreased by 3.3 (p = 0.01). This reduction was equally detected in all
      subscores. In a few patients, blistering and burning sensation after some
      sessions were noted. CONCLUSION: Localized UVB phototherapy is an effective
      treatment option for persistent plaques of psoriasis. Compared with conventional
      UVB, localized phototherapy has the added safety benefit of virtually eliminating
      unwanted exposure of the healthy tissue to UVB.

PMID- 16096184
TI  - Efficacy of 2 weeks' application of theophylline ointment in psoriasis vulgaris.

PMID- 16096185
TI  - A reappraisal of the concept of suppressive versus remittive psoriasis
      treatments.
AB  - Among the ways to characterize the many treatments for psoriasis is to
      distinguish suppressive from remittive therapies. Remittive therapies are thought
      to be treatments that result in a prolonged period of disease remission even
      after stopping the drug, while suppressive treatments are thought to work only
      during the treatment period. However, apparent differences in remittive and
      suppressive properties may be due to the remitting and relapsing nature of
      psoriasis and the order in which treatments are used in patients. Few clinical
      trials have compared the suppressive versus remittive properties of different
      treatments. Given the adverse events and expense associated with many psoriasis
      therapies, a major implication is that psoriasis patients who have cleared on
      therapy should probably be tested at intervals to see if they can be tapered off
      their medication without loss of control of their disease.

PMID- 16096186
TI  - Assessing the therapeutic benefits of antihistamines for the treatment of chronic
      idiopathic urticaria--a requirement for well-designed comparative clinical
      studies.

PMID- 16096187
TI  - Topical capsaicin for the treatment of acute lipodermatosclerosis and lobular
      panniculitis.
AB  - Topical capsaicin is well known to reduce nociceptive pain and neurogenic
      inflammation by depleting substance P. Its fibrinolytic and antithrombotic
      effects are less well known. We report two cases of acute lipodermatosclerosis
      which did not respond to several conventional treatment regimens and one case of
      acute lobular panniculitis in a pregnant woman with venous insufficiency, who
      were successfully treated within a short period of 3 weeks with topical 0.075%
      capsaicin cream.

PMID- 16096189
TI  - Predictors of young adults' representations of and behavior in their current
      romantic relationship: prospective tests of the prototype hypothesis.
AB  - Although attachment theory suggests that childhood experiences with caregivers
      serve as a prototype for adult love relationships, few explicit tests of this
      hypothesis exist in the literature. Drawing on data from a longitudinal cohort
      followed from birth to young adulthood, this paper examined correlates and
      antecedents of young adults' representations of and behavior in their current
      romantic relationship. Young adults who experienced a secure relationship with
      their primary caregiver in infancy as assessed in the Strange Situation were more
      likely to (a) produce coherent discourse regarding their current romantic
      partnership in the context of the Current Relationship Interview (CRI) and (b)
      have a higher quality romantic relationship as observed in standard conflict and
      collaboration tasks. Infant security accounted for variation in CRI security
      above and beyond the observed quality of participants' current romantic
      relationship. In contrast, the association between infant and romantic security
      was partially mediated by individuals' self-reports about their romantic
      experiences, suggesting that one plausible mechanism by which early experiences
      with caregivers shape young adults' representations of their attachments with
      romantic partners is through adults' expectations for and perceptions of love
      relationships.

PMID- 16096190
TI  - Couple attachment and the quality of marital relationships: method and concept in
      the validation of the new couple attachment interview and coding system.
AB  - This study investigates links between adult attachment and marital quality in 73
      married couples, using a new Couple Attachment Interview that was modeled after
      the Adult Attachment Interview but focuses on the relationship between the
      partners. A coding system (CAICS) comparing the interview protocol to prototypes
      for secure, dismissing, and preoccupied attachment styles yielded continuous
      ratings of all three styles, and categorical classifications of secure/insecure
      for each partner. The study found direct links between couple attachment and both
      self-reported and observed marital quality, with all three continuous scores
      contributing uniquely to the equations. In most cases, the continuous scores
      explained variation in marital quality after the categorical security scores were
      entered into the regressions, although categorical scores also contributed
      uniquely to the explanation of marital quality. Pairing of partners' scores
      explained significant variance in both self-reported and observed evaluations of
      the couple relationship. Security of couple attachment served as a mediator in
      the link between self-reported marital satisfaction and observed marital quality.
      The results illustrated the interconnection of methodological choices and
      theoretical advances in the study of attachment and couple relationship quality.

PMID- 16096191
TI  - Understanding the link between maternal adult attachment classifications and
      thoughts and feelings about emotions.
AB  - The purpose of this study was to examine the associations between maternal
      representations of attachment, as assessed with the Adult Attachment Interview
      (AAI; George, Kaplan, & Main, 1996), and mothers' thoughts and feelings about
      their own emotions and emotions emerging in their toddlers. Eighty-nine
      adolescent mothers completed the AAI and the Center for Epidemiological Studies
      Depression Scale (CES-D; Radloff, 1977) and Katz, Gottman, Shapiro, and Carrere's
      (1997) meta-emotion interview for parents of toddlers. Autonomous mothers
      demonstrated the most open and flexible mindset around a variety of emotions in
      themselves and their toddlers. Dismissing mothers exhibited a tendency to
      minimize internalizing emotions in themselves and their children, while
      unresolved mothers described the most emotion regulatory difficulties.

PMID- 16096192
TI  - Leaving home for college: a potentially stressful event for adolescents with
      preoccupied attachment patterns.
AB  - Sixty-two high school students, 28 of which were planning on leaving home to
      attend college, completed the Adult Attachment Interview and self-report
      questionnaires pertaining to their relationship with their parents. Compared to
      their autonomous counterparts, preoccupied students who had left home reported
      having a more negative relationship with each parent and experiencing more family
      related stress. However, they reported having more contact with each parent. In
      contrast, no attachment differences with regards to perceptions of the parent
      adolescent relationship were found among students who lived at home while in
      college. This suggests that individual differences related to attachment state of
      mind in adolescence may be magnified by a stressful life experience.

PMID- 16096193
TI  - Representations of attachment to parents and shyness as predictors of children's
      relationships with teachers and peer competence in preschool.
AB  - In a group of 112 children (46% boys), representations of attachment to parents
      and shyness at age 5 were used as predictors of social relationships in preschool
      at age 6. A Story Completion task was used to assess attachment representations
      and shyness was assessed through parent ratings and observations. Preschool
      teachers rated the child-teacher relationship and the child's peer competence.
      Children with avoidant representations had more conflictual and less close
      teacher relationships, and showed less prosocial orientation with peers than did
      children with secure attachment representations. Children with bizarre-ambivalent
      representations had somewhat less intimate teacher relationships and less social
      initiative with peers than did children with secure representations. Shy children
      had less close and less conflictual teacher relationships and somewhat less
      social initiative with peers than did non-shy children. There was one marginally
      significant interaction effect of the quality of attachment representations and
      shyness on social relationships.

PMID- 16096194
TI  - Timing effects on first marriage: twentieth-century experience in England and
      Wales and the USA.
AB  - Recent substantial declines in first marriage in Western countries have been
      accompanied by increases in the average age at first marriage. Since the period
      proportion ever marrying, PEM, is sensitive to cohort tempo changes, the recent
      fall in the PEM may simply reflect cohort delays in marriage. The importance of
      timing factors is examined in the light of twentieth-century experience of first
      marriage in England and Wales and the USA. Using a variant of the Timing Index
      developed in research on fertility, we measure cohort timing effects for marriage
      and calculate an adjusted PEM. After examining twentieth-century trends in
      nuptiality for men and women, we find substantial tempo effects on the period
      PEM. Adjusted PEM values show a real decline in marriage for cohorts, but that
      decline is considerably smaller than the one shown by the unadjusted figures.
      This is especially true for England and Wales, where the decline in marriage was
      much greater.

PMID- 16096195
TI  - The measurement of historical trends in fetal mortality in England and Wales.
AB  - This paper critically discusses recent attempts to estimate long-term trends in
      the stillbirth rate for England and Wales. It assesses the available historical
      evidence for the level of late-fetal mortality, drawing especially on examples
      from Norway, Sweden, and Denmark. A theoretical fetal-infant life table for a
      high-mortality population is also outlined as a means of analysing the
      relationship between segments of the conception-to-first-birthday mortality
      curve. Finally, new estimates of the stillbirth rate for England and Wales are
      proposed, based on variations in the early neonatal and maternal mortality rates
      during the 1930s. These estimates are substantially lower than the earlier
      estimates and are more in keeping with the available evidence from northern
      Europe. The implications of the revised estimates for interpretations of
      historical changes in mortality patterns are also considered.

PMID- 16096196
TI  - Educational stratification among Arabs and Jews in Israel: historical
      disadvantage, discrimination, and opportunity.
AB  - Arabs in Israel are a heterogeneous but largely underprivileged minority with a
      history of disadvantage in several domains, including education and employment.
      In this paper, we document changes in their attainment of various educational
      levels across cohorts born from the mid-1920s to the 1970s. We make comparisons
      among different Arab religious groups, between men and women, and between Arabs
      and the majority Jewish populations in Israel. We find that over consecutive
      birth cohorts, substantial ethnic differences in educational attainment have
      narrowed at the lower levels of schooling, but have increased at higher levels.
      Moreover, the results indicate that the disadvantage of Muslim Arabs in terms of
      entry into and completion of high school can be accounted for only partially by
      differences in the social status of their parents and characteristics of their
      neighbourhoods. The findings suggest that long-term historical differences among
      groups and discriminatory practices towards Arabs are important factors in
      explanations of disparities in educational attainment.

PMID- 16096197
TI  - Intergenerational transfers of resources between older persons and extended kin
      in Taiwan and the Philippines.
AB  - This study examines the extent to which older generations actively exchange
      resources with extended kin in Taiwan and the Philippines. It is critical to
      understand the position of older generations in the family, because population
      ageing and declines in family size spur concerns about the tenacity of family
      support. This research builds upon previous studies that have predominantly
      focused on parent-child relationships alone or on support received by older
      parents. Social-network measures are used to estimate overall levels of transfers
      of resources across generations, and the prevalence and patterns of pathways that
      link generations and types of kin. Our findings show that the availability of kin
      is similar in both settings but that transfer activity in the Philippines appears
      more broadly distributed across family relations, especially siblings, while in
      Taiwan transfers are more concentrated among lineal kin. These results confirm
      the importance and diversity of extended kin in systems of family support.

PMID- 16096198
TI  - Men's influence on the onset and progress of fertility decline in Ghana, 1988-98.
AB  - While lower fertility is commonly associated with women's reproductive autonomy,
      we demonstrate that the influence of men's education on reproductive decision
      making increased during the first decade of rapid fertility decline in Ghana.
      Husband's education exerts a stronger influence on wife's fertility intentions
      than does her own education, and the magnitude of the effect of his education
      increased significantly from 1988 to 1998. Lower fertility in Ghana seems to be
      associated more with men's declining fertility desires than with women's
      increasing reproductive autonomy. Nevertheless, there is some indication that
      women's education may play a relatively greater role in reproductive decision
      making as fertility decline progresses still further.

PMID- 16096199
TI  - Has the reciprocal relationship between employment and marriage changed for men?
      An analysis of the life histories of men born in The Netherlands between 1930 and
      1970.
AB  - The study presented here analyses the reciprocal relationship for men between
      employment career and union formation and examines whether this relationship
      changed across twentieth-century birth cohorts. Competing hypotheses about trends
      are described, using notions of role-specialization, spouse support, and
      uncertainty. The study is based on an investigation of the life histories of
      2,795 men in the Netherlands who were born between the 1930s and the 1960s, and
      confirms earlier findings by showing that employment fosters marriage while
      marriage protects men from becoming unemployed. There is also a relationship
      between employment and cohabitation but it is weaker in both directions. However,
      the relationship between marriage or cohabitation and occupational mobility is
      less clear, suggesting that the economic benefits of marriage cannot be
      generalized to the occupational domain. Although it is commonly believed that the
      link for men between career and marriage has weakened over time, our comparison
      of birth cohorts shows that in fact this is not the case.

PMID- 16096200
TI  - A note on the cohort-fertility analysis in the paper 'Patterns of low and lowest
      low fertility in Europe', Population Studies 58(2): 161-176, by Francesco C.
      Billari and Hans-Peter Kohler.

PMID- 16096201
TI  - Reply to the note by Frejka and Sardon on our paper 'Patterns of low and lowest
      low fertility in Europe' and an erratum.

PMID- 16096202
TI  - Fogel and the history of mortality.

PMID- 16096206
TI  - The global problem of genetic disease.
AB  - Inherited haemoglobin disorders will undoubtedly cause an increasing health
      burden in many developing countries. Although much is known about their molecular
      pathology and the mechanisms for their phenotypic diversity, many important
      questions remain, not least the role of the environment in modifying the clinical
      course. Methods for screening these conditions are now well established and
      inexpensive and it is vital that they are applied to define the magnitude of the
      problem that will be posed by these conditions in the future. Similarly, they
      form the basis for widespread screening and counselling programmes directed at
      developing prenatal diagnosis expertise where this is not available. Answers to
      some relatively simple questions about the role of the environment could also
      make a major difference to the management of the haemoglobin disorders. There is
      a major case for the development of regional networks to apply such technology as
      has been developed for the control and prevention of the important haemoglobin
      disorders, particularly in Asian countries.

PMID- 16096207
TI  - Alpha-thalassaemia and population health in Southeast Asia.
AB  - Alpha-thalassaemia mutations are common. In Southeast Asia, they cause Hb H
      disease and Hb Barts hydrops fetalis. Fetuses with the devastating Hb Barts
      hydrops fetalis due to the complete lack of alpha-globin gene die in utero or
      shortly after birth, often during the second or third trimesters. Recent findings
      on patients with Hb H disease who have only one active alpha-globin gene suggest
      that it is not necessarily a benign disorder as previously thought. The disease
      burden of these syndromes and their public health importance have been largely
      neglected. We review the population carrier frequencies of alpha-thalassaemia,
      and summarize the clinical features, diagnostic approaches, counselling and
      management of these common genetic disorders. Several practical proposals are
      made that, if implemented, can begin to address the issues of collaboration and
      improvement for care of these common diseases in the region.

PMID- 16096208
TI  - Prevention of thalassaemia and haemoglobinopathies in remote and isolated
      communities--the Maldives experience.
AB  - The Maldives comprises 1192 islands covering a land mass that amounts to under 1%
      of the total geographical territory of the country. The population of 280,000 is
      dispersed across 200 isolated communities, with an average of 1000 people per
      community. Recent progress in health terms include a reduction in the infant
      mortality rate from 62 in 1992 to 14 in 2003, and 95% coverage in child
      immunization. In 1992, SHE a non-governmental organization established that the
      beta-thalassaemia prevalence rate was 18.1% (1 in 5) and on the basis of the
      result, launched a nationwide awareness and population screening programme,
      visiting each island in the Maldives every 5 years and targeting 12-35-year-olds.
      Screening of 100 cord blood samples indicated a 28% incidence of alpha
      thalassaemia. Screening results highlighted significantly high incidence of more
      than one haemoglobinopathy on individual islands. This is of particular
      importance given the norm of intra-island marriages. Specific mutation analysis
      showed that three mutations accounted for more than 95% of the thalassaemia
      genes, ensuring a high detection rate and cost effectiveness of a prenatal
      diagnosis programme. Outcomes of the screening programme include screening of
      more than 25% of the target population; the establishment of a Government
      National Thalassaemia Centre; inclusion of thalassaemia into the school
      curriculum; the legal requirement for screening prior to marriage; legalization
      of prenatal diagnosis and medical termination of pregnancy; and the commencement
      of prenatal diagnostic services. The programme successes include effective
      advocacy, resource mobilization, motivation for screening, voluntary blood
      donation, and thalassaemia becoming a household word in the country.

PMID- 16096209
TI  - Establishment of prenatal diagnosis for beta-thalassaemia: a step towards its
      control in a developing country.
AB  - Beta-thalassaemia constitutes a major health burden on the limited health
      resources of India and prenatal diagnosis is seen as an important preventive
      measure to reduce the burden of the disease. Prenatal diagnosis has been offered
      to 99 women in 112 pregnancies by fetal DNA analysis, using a PCR-based
      Amplification Refractory Mutation System (ARMS) for the common and uncommon
      Indian mutations. Restriction fragment length polymorphism (RFLP) for the beta
      globin gene was used when the mutation remained unidentified in one of the
      parents or to complement the ARMS result. In 53 cases the fetus tested had beta
      thalassaemia trait (betaTT) (47.3%), 22 were normal (19.6%) and 31 had
      thalassaemia major (27.6%). In five cases (4.5%), a definitive report could not
      be given due to maternal contamination. In one case (0.9%), there was a
      misdiagnosis. Pitfalls encountered in the diagnosis were maternal contamination
      and occasional non-amplification of the primers. Having established a regional
      centre for the prenatal diagnosis for thalassaemia, the screening programmes will
      be enlarged both to identify carriers and prevent the birth of further homozygous
      children, even during the first pregnancy.

PMID- 16096210
TI  - The effect of religious, cultural and social identity on population genetic
      structure among Muslims in Pakistan.
AB  - Knowledge of historical demography and contemporary social stratification can be
      valuable in understanding disease patterns, including genetic disorders,
      especially in communities that have a high prevalence of endogamous and/or
      consanguineous marriages. This paper provides a background to the religious,
      historical and socio-cultural factors that have helped define the bounds of
      endogamy for Muslims in undivided India and more specifically since the creation
      of Pakistan. The preference for endogamous marriage is based on the clan-oriented
      nature of the society, which values and actively seeks similarities in social
      group identity based on several factors, including religious, sectarian, ethnic,
      and tribal/clan affiliation. Religious affiliation is itself multi-layered and
      includes religious considerations other than being Muslim, such as sectarian
      identity (e.g. Shia or Sunni, etc.) and religious orientation within the sect
      (Isnashari, Ismaili, Ahmedi, etc.). Both ethnic affiliation (e.g. Sindhi, Baloch,
      Punjabi, etc.) and membership of specific biraderis or zat/quoms are additional
      integral components of social identity. Within the bounds of endogamy defined by
      the above parameters, close consanguineous unions are preferential due to a
      congruence of key features of group- and individual-level background factors.

PMID- 16096211
TI  - A population genetics perspective of the Indus Valley through uniparentally
      inherited markers.
AB  - Analysis of mtDNA and Y-chromosome variation in the Indo-Gangetic plains shows
      that it was a region where genetic components of different geographical origins
      (from west, east and south) met. The genetic architecture of the populations now
      living in the area comprise genetic components dating back to different time
      periods during the Palaeolithic and the Neolithic. mtDNA data analysis has
      demonstrated a number of deep-rooting lineages of Pleistocene origin that may be
      witness to the arrival of the first settlers of South and Southwest Asia after
      humans left Africa around 60,000 YBP. In addition, comparisons of Y-chromosome
      and mtDNA data have indicated a number of recent and sexually asymmetrical
      demographic events, such as the migrations of the Parsis from Iran to India, and
      the maternal traces of the East African slave trade.

PMID- 16096212
TI  - Genetic studies in the Amish community.
AB  - The Amish community was established in Pennsylvania, Ohio and Indiana. They form
      a distinct and biologically isolated community by virtue of their strong cultural
      and religious beliefs. This paper outlines aspects of the Amish culture and
      reviews some of the recent genetic studies that have been undertaken in this
      community.

PMID- 16096213
TI  - Oculocutaneous albinism in southern Africa: population structure, health and
      genetic care.
AB  - BACKGROUND: People with oculocutaneous albinism (OCA) have reduced levels of
      melanin in their hair, skin and eyes, with associated visual impairment and
      extreme sun sensitivity requiring lifelong monitoring. This genetic condition is
      surrounded by myth, superstition and fear in Africa, where affected individuals
      and their families may be rejected, shunned and excluded from their community.
      OBJECTIVE: This review reports population studies in southern Africa to determine
      the distribution of people with OCA in this predominantly rural and relatively
      impoverished area-crucial information for health and education providers. Health
      and genetic care studies document the range of eye and skin problems experienced
      and suggest effective and sustainable ways to manage these needs in a low
      resource setting. CONCLUSION: Innovative genetic care programmes in northern
      South Africa facilitate low-cost management of albinism, raise self-esteem and
      promote community awareness, helping to improve the long-term health prospects
      and social integration of those affected. This holistic approach of dealing with
      albinism from both a medical and a sociological perspective could be applied in
      other areas of Africa where this condition is prevalent.

PMID- 16096214
TI  - Strategies for the prevention of hereditary diseases in a highly consanguineous
      population.
AB  - Autosomal recessive hereditary diseases are relatively common in the Saudi
      population. The consanguinity rate is in excess of 50% and is a practice that
      remains strongly embedded within Saudi culture. The impact of this practice is
      recognized and is being addressed. Early detection and treatment of diseases can
      reduce mortality and minimize morbidity. This is the basis of successful neonatal
      screening for inborn errors of metabolism where treatment or modification of
      lifestyle can modulate disease. Ultimately, understanding the genetics of these
      diseases will provide opportunities for prevention. Options such as prenatal
      screening can be used to reduce the incidence of live births with inherited
      diseases. However, prenatal diagnosis and associated intervention is unacceptable
      to wide sections of all societies. Carrier detection and genetic counselling
      programmes have been very successful in reducing the incidence of inherited
      disorders in many populations. These programmes are most successful when they are
      sensitive to the cultural backgrounds of populations in which they are applied.
      In Saudi society, premarital screening to identify carrier status and the
      provision of appropriate counselling has tremendous potential to prevent
      inherited disease.

PMID- 16096215
TI  - A population-based study of birth defects in Malaysia.
AB  - Birth defects are one of the leading causes of paediatric disability and
      mortality in developed and developing countries. Data on birth defects from
      population-based studies originating from developing countries are lacking. One
      of the objectives of this study was to determine the epidemiology of major birth
      defects in births during the perinatal period in Kinta district, Perak, Malaysia
      over a 14-month period, using a population-based birth defect register. There
      were 253 babies with major birth defects in 17,720 births, giving an incidence of
      14.3/1000 births, a birth prevalence of 1 in 70. There were 80 babies with
      multiple birth defects and 173 with isolated birth defects. The exact syndromic
      diagnosis of the babies with multiple birth defects could not be identified in 18
      (22.5%) babies. The main organ systems involved in the isolated birth defects
      were cardiovascular (13.8%), cleft lip and palate (11.9%), clubfeet (9.1%),
      central nervous system (CNS) (including neural tube defects) (7.9%),
      musculoskeletal (5.5%) and gastrointestinal systems (4.7%), and hydrops fetalis
      (4.3%). The babies with major birth defects were associated with lower birth
      weights, premature deliveries, higher Caesarean section rates, prolonged
      hospitalization and increased specialist care. Among the cohort of babies with
      major birth defects, the mortality rate was 25.2% during the perinatal period.
      Mothers with affected babies were associated with advanced maternal age, birth
      defects themselves or their relatives but not in their other offspring, and
      significantly higher rates of previous abortions. The consanguinity rate of 2.4%
      was twice that of the control population. It is concluded that a birth defects
      register is needed to monitor these developments and future interventional trials
      are needed to reduce birth defects in Malaysia.

PMID- 16096216
TI  - Genetic disorders in a paediatric hospital in Cambodia.
AB  - Cambodia is an extremely underdeveloped country in Southeast Asia with a
      childhood mortality rate of 105/1000 live births. Angkor Hospital for Children is
      a paediatric teaching hospital in Siem Reap, northwest Cambodia, which serves as
      the provincial paediatric department but also sees children from provinces
      throughout northern Cambodia, and with training provided for health workers from
      all parts of the country. The impact of genetic disease on this paediatric
      population is discussed, addressing the areas of haematology (including
      thalassaemia and other haemoglobinopathies, glucose-6-phosphate deficiency and
      bleeding disorders), multifactorial disorders (cleft palate, congenital heart
      disease and neural tube defects), and uncommon genetic disorders and chromosomal
      syndromes. In the future, as low-income countries develop and their burden of
      infectious disease begins to subside, the contribution of these disorders to
      paediatric morbidity and mortality will become increasingly apparent. This
      transition needs to be considered in the allocation of health resources and in
      the structuring of undergraduate and postgraduate medical education.

PMID- 16096217
TI  - A community genetics approach to population screening in India for mental
      retardation--a model for developing countries.
AB  - Some 0.55 million people living in semi-urban and slum populations were screened
      for mental retardation by trained primary health centre (PHC) doctors, nurses and
      community health volunteers (CHVs). The staff were provided with prior training
      on the detection, prevention and diagnosis of mental retardation, prenatal
      diagnosis, and reproductive responsibilities. Field visits were employed to
      confirm diagnosed developmental disabilities, and demographic data incorporating
      social maps of 14 PHCs were prepared. Cases with high-risk genetic factors
      detected by PHC staff were referred to the Centre for Research in Mental
      Retardation (CREMERE) for cytogenetic and metabolic investigations, thus linking
      the study population and the Referral Centre. A genetic team interacted with the
      patient and family members for genetic counselling. Mental retardation was
      confirmed in 511 of the 525 cases reported, reflecting the positive impact of
      training on the CHVs. Potentially preventable environmental factors, such as
      birth asphyxia, infections, and low birth weight were identified in 251 cases
      (49%), 137 (27%) of which had additional genetic factors. Genetic causes were
      found in 186 (36%) individuals, the most common being Down syndrome. The study
      illustrates the urgent need for the integration of genetic screening into the
      public health services in India.

PMID- 16096218
TI  - Ethnicity, equity, and access to genetic services--the UK perspective.
AB  - The UK is a multi-ethnic, multicultural society with over 300 languages spoken in
      the capital (London) alone. This short report explores the implications of a
      diverse population on health and access to genetic services. It considers
      genetic, cultural and linguistic differences, and provides evidence of
      inequalities in access. Following recent legislation promoting race equality, the
      report highlights current activities and shortfalls, and proposes recommendations
      towards achieving greater equity of access within the context of clinical
      genetics service provision.

PMID- 16096219
TI  - Genetics education in a culturally diverse population--lessons learnt, future
      directions.
AB  - To provide equitable genetics education services, the needs of a culturally and
      linguistically diverse (CALD) population must be addressed. The mission of the
      Centre for Genetics Education (CGE) in Australia articulates a commitment to
      fostering community partnerships, implementing educational strategies and
      evaluating the impact of genetics information and technology on society. The aim
      of this report is to review the ways in which CALD groups have been partners in
      the planning and implementation of genetics educational strategies of the Centre.
      Responding to the community and respecting its contribution has helped forge
      these partnerships and implement appropriate and relevant educational strategies.
      The partnerships have been effective in modulating both the protocols used in
      producing resources, the resource content itself, and the provision of more
      appropriately targeted resources for these community groups.

PMID- 16096220
TI  - The GRAIDS Trial: the development and evaluation of computer decision support for
      cancer genetic risk assessment in primary care.
AB  - The development and evaluation of computer decision support for the assessment of
      cancer genetic risk in primary care is reported with two series of studies
      described: the RAGs (Risk Assessment in Genetics) studies and the GRAIDS (Genetic
      Risk Assessment in an Intranet and Decision Support) Trial. In the GRAIDS Trial,
      45 general practices in Eastern England have been recruited and randomised.
      Comparison practices attend an educational session and receive clinical
      guidelines about familial breast and colorectal cancer. In the intervention
      practices a lead clinician is trained in cancer genetics and use of the GRAIDS
      software. The GRAIDS software is a simple pedigree-drawing program that
      implements clinical guidelines for familial breast and colorectal cancer and
      presents individualised information about breast cancer risk in a range of
      formats. Outcome measures of the trial include: frequency of software use,
      practitioners' attitudes towards the software, total number of referrals to
      secondary care about familial cancer and the proportion that meet regional
      referral criteria, and a patient-centred measure of informed decision making. The
      family history will become an increasingly important tool in primary care to
      assess genetic risk. This research evaluates an approach to support high-quality
      advice about cancer genetics in primary care which could be applied more broadly
      as our understanding of complex disease genetics increases.

PMID- 16096221
TI  - InterRett--The application of bioinformatics to International Rett syndrome
      research.
AB  - InterRett, International Rett Syndrome Association (IRSA) Rett Phenotype
      Database, is a unique international project funded by the IRSA, which brings
      together child neurologists, geneticists, paediatricians, epidemiologists,
      researchers and families of affected children. The principal aim of InterRett is
      to increase the clinical understanding of Rett syndrome throughout the world and
      with the statistical power of large case numbers, determine any correlations
      between genotype and the phenotypic characteristics. Since establishment of the
      database in January 2003, InterRett has registered 286 cases from 24 countries,
      with family questionnaire data submitted on 242 cases and clinician data on 116
      cases. Collated de-identified data gathered from families and clinicians have
      been incorporated into a searchable online database allowing simple and complex
      interrogation of the clinical phenotype information. InterRett will also serve as
      a clearing house for data to encourage inter-country collaboration between
      researchers and negotiations are in place with several countries for data
      contributions in excess of 1000 cases. The resulting online database will be an
      invaluable resource for understanding the nature and management of Rett syndrome,
      as well as providing a model for other rare childhood disorders.

PMID- 16096222
TI  - IDEA (Intellectual Disability Exploring Answers): a population-based database for
      intellectual disability in Western Australia.
AB  - Despite the demands it places on individuals, families and the community,
      intellectual disability (ID) is a neglected area of public health. Accurate
      estimates of prevalence are sparse and range from 0.5 to 3.0%. The cause of the
      condition is unknown in at least 50% of cases. This paper describes the
      Intellectual Disability Exploring Answers (IDEA) database set up in Western
      Australia to provide an infrastructure for research and to facilitate the
      planning of service provision for people with ID. Since 1953 a database for ID
      has been maintained in Western Australia, a state with a population of 1.95
      million in an area of 2.52 million km2. The current IDEA database aims to obtain
      ongoing population-based ascertainment of ID from providers of clinical and
      educational services, with the potential for linkage to a network of other state
      databases. The average prevalence of ID for children born in Western Australia
      over the years 1983-1996 was 15.2 per 1000 live births, with 50% ascertained only
      through the education system. During this time period 60% of cases were male. Of
      children with an ID born in Western Australia in 1980-1999 and surviving to 1
      year, 30.1% had a birth defect, and the prevalence ratio of birth defects in this
      group compared to the population with no birth defects was 6.5 (CI 6.3-6.8).

PMID- 16096225
TI  - Assessing the benefits of using assistive technologies and other supports for
      thinking, remembering and learning.
AB  - PURPOSE: Planning assistive technologies and other supports for individuals with
      cognitive disabilities requires a comprehensive and individualized assessment of
      current goals, past experiences with the use of technologies and other supports,
      and the person's predisposition to the use of alternative or additional supports.
      This paper discusses a foundation for the refinement of an existing assessment
      process to match technologies to individuals with cognitive disabilities. METHOD:
      Prior research and a literature review identified the critical needs for an
      assessment process that would serve to identify key elements known to influence
      the success use of assistive technology and other supports by persons with
      cognitive disabilities. RESULTS: The components of successful, effective and
      satisfied support use result from a good match of device and support features,
      user goals and preferences, and environmental resources. The relationship to the
      World Health Organization's International Classification of Functioning,
      Disability and Health and the International Standardization Organization's
      international standard ISO DIS 9999 is discussed. CONCLUSIONS: As the number of
      assistive technology options increase, individualized interventions for
      individuals with cognitive disabilities will be easier to accomplish. The key to
      successful and optimal use of these products will be an appropriate and
      comprehensive assessment of consumer needs and preferences and the identification
      of additional accommodations and supports.

PMID- 16096226
TI  - Age differences in mental scanning of locomotor maps.
AB  - PURPOSE: To investigate whether the metric quality of mental spatial
      representations of the environment changes with aging, by means of mental
      scanning of locomotor space. METHOD: Twenty young adults (age 21.1-30.8) and 20
      old adults (age 60.4-76.4) were submitted to a battery of psychometric tests to
      assess the effects of aging on general cognitive functions and specific visuo
      spatial abilities, and to determine which cognitive factors correlated with
      scanning performance. The mental scanning task followed. Participants firstly had
      to learn a path comprising six positions by walking and observing these;
      secondly, they had to use mental imagery to scan from a first to a second
      position, according to different distances. RESULTS: Aging reduces the validity
      of the metric information incorporated by mental spatial representations.
      Attentional and working memory resources, ability to manipulate spatial
      information and a general factor of abstract visuo-spatial reasoning strongly
      correlated with scanning performance. Finally, aging seemed to have a selective
      effect on cognitive functioning. CONCLUSIONS: Age differences emerge when
      demanding storage and processing of information are simultaneously required, as
      predicted by the Limited Resources view of aged cognition.

PMID- 16096227
TI  - Enhanced self-localization by auditory cues in blind humans.
AB  - PURPOSE: Investigate the involvement of auditory spatial compensation, which is
      observed in blind humans, in self-localization processes. METHOD: Sighted and
      early-blind subjects had to indicate, on a two-dimensional view of the
      experimental room, the position where they previously sat and had passively
      listened to auditory spatial cues. Two different environments were distinguished.
      In a first session, auditory cues (i.e., white broadband sounds) were displayed
      successively in a dark anechoic room. This condition was defined as a simple
      acoustic environment. In a second session, four different auditory cues were
      displayed simultaneously at regular intervals in an experimental room, where echo
      cues were salient. This condition, which is more reminiscent of the natural
      situation, was described as a complex acoustic environment. RESULTS: Self
      localization capacities were significantly better in early-blind individuals than
      in sighted subjects, whatever the type of acoustic environment. CONCLUSIONS:
      Auditory compensation leads to improved self-localization capacities in early
      blind humans and indicates that prior visual experience is not essential for the
      development of spatial competence.

PMID- 16096228
TI  - The head-centered meridian effect: auditory attention orienting in conditions of
      impaired visuo-spatial information.
AB  - This paper examines the characteristics of spatial attention orienting in
      situations of visual impairment. Two groups of subjects, respectively
      schizophrenic and blind, with different degrees of visual spatial information
      impairment, were tested. In Experiment 1, the schizophrenic subjects were
      instructed to detect an auditory target, which was preceded by a visual cue. The
      cue could appear in the same location as the target, separated from it
      respectively by the vertical visual meridian (VM), the vertical head-centered
      meridian (HCM) or another meridian. Similarly to normal subjects tested with the
      same paradigm (Ferlazzo, Couyoumdjian, Padovani, and Olivetti Belardinelli,
      2002), schizophrenic subjects showed slower reactions times (RTs) when cued, and
      when the target locations were on the opposite sides of the HCM. This HCM effect
      strengthens the assumption that different auditory and visual spatial maps
      underlie the representation of attention orienting mechanisms. In Experiment 2,
      blind subjects were asked to detect an auditory target, which had been preceded
      by an auditory cue, while staring at an imaginary point. The point was located
      either to the left or to the right, in order to control for ocular movements and
      maintain the dissociation between the HCM and the VM. Differences between
      crossing and no-crossing conditions of HCM were not found. Therefore it is
      possible to consider the HCM effect as a consequence of the interaction between
      visual and auditory modalities. Related theoretical issues are also discussed.

PMID- 16096229
TI  - A relative access measure to identify barriers to efficient transit use by
      persons with visual impairments.
AB  - PURPOSE: Persons with visual impairments or blindness can face significant
      restrictions to their efficient travel, especially when attempting transit
      transfers and using a large, multi-modal terminal. Little is known about what
      makes some tasks much harder than others. This paper presents an approach to
      empirically measure the difficulty of a variety of transit tasks. METHOD: An
      experiment was conducted at an urban transit terminal, with three other transit
      modes nearby. Thirty persons with visual impairments attempted to make five
      simulated transfers between these modes. Errors and time to complete these tasks
      were collected in order to quantify the nature of various barriers to efficient
      travel for this group. In total, 20 locations were visited. Completion times were
      compared to a sighted traveler to determine a measure of the time penalty, or
      'relative access measure.' RESULTS: Two basic findings are reported. Empirical
      data showed that different types of transit tasks and locations had a wide range
      of difficulty and inherent time penalties. Some tasks like crossing a difficult
      street, finding unmarked track doors, and finding inconsistently placed amenities
      were quite time consuming and sometimes impossible to accomplish. Other tasks,
      like walking to a street corner and crossing a simpler street, had much lower
      penalties and could be completed with ease. CONCLUSIONS: The placement of
      additional cues, those of identity and direction, provided with auditory signage,
      were able to eliminate much of the uncertainty and time restrictions associates
      with transit use and navigation for persons with visual impairments.

PMID- 16096230
TI  - Checking an integrated model of web accessibility and usability evaluation for
      disabled people.
AB  - A combined objective-oriented and subjective-oriented method for evaluating
      accessibility and usability of web pages for students with disability was tested.
      The objective-oriented approach is devoted to verifying the conformity of
      interfaces to standard rules stated by national and international organizations
      responsible for web technology standardization, such as W3C. Conversely, the
      subjective-oriented approach allows assessing how the final users interact with
      the artificial system, accessing levels of user satisfaction based on personal
      factors and environmental barriers. Five kinds of measurements were applied as
      objective-oriented and subjective-oriented tests. Objective-oriented evaluations
      were performed on the Help Desk web page for students with disability, included
      in the website of a large Italian state university. Subjective-oriented tests
      were administered to 19 students labeled as disabled on the basis of their own
      declaration at the University enrolment: 13 students were tested by means of the
      SUMI test and six students by means of the 'Cooperative evaluation'. Objective
      oriented and subjective-oriented methods highlighted different and sometimes
      conflicting results. Both methods have pointed out much more consistency
      regarding levels of accessibility than of usability. Since usability is largely
      affected by individual differences in user's own (dis)abilities, subjective
      oriented measures underscored the fact that blind students encountered much more
      web surfing difficulties.

PMID- 16096231
TI  - Strength and endurance of knee extensors in subjects after paralytic
      poliomyelitis.
AB  - PURPOSE: To compare the strength and endurance of knee extensors in subjects
      after paralytic poliomyelitis as well as to extend the comparison to healthy
      subjects. METHOD: Twenty subjects after poliomyelitis with new symptoms (SYM
      group), 10 without new symptoms (ASYM group) and 15 healthy controls were
      included. To determine strength, isometric maximal voluntary contraction (MVC)
      torque of knee extensors in both legs was determined by Biodex dynamometer at 60
      degrees knee angle. To determine endurance, the subjects were asked to maintain
      force in the knee extensors in the same position, in the range between 40-45% of
      MVC torque, as long as possible. The 'tensiomyography' method was applied to
      measure the radial displacement of m. rectus femoris during submaximal continuous
      electrical stimulation until recording a flat response. RESULTS: No significant
      difference in MVC torque and endurance was found between SYM and ASYM group, as
      well between the duration of m. rectus femoris response of both groups to
      submaximal electrical stimulation. MVC torque and endurance of knee extensors
      with 'normal' strength was significantly lower in post-polio subjects compared to
      healthy controls. CONCLUSION: Endurance of knee extensor muscles in post-polio
      subjects is generally and significantly lower than that of knee extensors in
      healthy subjects, regardless of the implication of normal strength and subjective
      observations of post-polio subjects.

PMID- 16096232
TI  - Measurement of cervical flexor endurance following whiplash.
AB  - AIM: To investigate measurement properties of a practical test of cervical flexor
      endurance (CFE) in whiplash patients including inter-rater reliability,
      sensitivity to clinical change, criterion related validity against the Neck
      Disability Index (NDI), and discriminant validity for injured versus uninjured
      populations. METHODS: Two samples were recruited, 81 whiplash patients, and a
      convenience sample of 160 subjects who were not seeking treatment and met
      criteria for normal pain and range of motion. CFE was measured using a stopwatch
      while the subject, in crook lying, held their head against gravity to fatigue.
      RESULTS: Inter-rater reliability in whiplash patients was in a range considered
      'almost perfect' (Intraclass Correlation=0.96). CFE had greater inter-subject
      variability than the NDI or range of motion in any of three planes. However, the
      effect size for improvement in CFE over treatment was as large as the effect
      sizes for all of those measures. In multivariate regression, CFE changes
      accounted for changes on the NDI better than the three ranges of motion. CFE
      discriminated whiplash patients who were within six months of injury (n=71) from
      age and gender matched normals with high effect size (ES=1.5). CONCLUSIONS: These
      findings provide evidence of reliability and validity for CFE measurement, and
      demonstrate that CFE detects clinical improvements. Variance on CFE emphasizes
      the need to consider inter-, and intra-subject standard deviations to interpret
      scores.

PMID- 16096233
TI  - Usefulness of BFB/EMG in facial palsy rehabilitation.
AB  - OBJECTIVE: To analyze and to compare the recovery and the development of
      synkinesis in patients with idiopathic facial palsy (Bell's palsy) following
      treatment with two methods of rehabilitation, kinesitherapy (KT) and
      biofeedback/EMG (BFB/EMG). STUDY DESIGN: Retrospective cases--series review.
      METHODS: Seventy-four patients with Bell' palsy were clinically evaluated within
      1 month from onset of palsy and at 12 months after palsy (House scale and
      synkinesis evaluation). Electromyography (EMG) and Electroneurography (ENG) were
      performed about 4 weeks after palsy to better evaluate functional abnormalities
      due to facial nerve lesion. The patients followed two different protocols for
      rehabilitation: the first 32 patients were treated with therapeutic exercises
      performed by therapists (KT group), the latter 42 patients were treated using
      BFB/EMG methods (BFB group) with inhibition of synkinetic movement as the primary
      goal. RESULTS: KT and BFB patients were evaluated for clinical and
      neurophysiological characteristics before rehabilitative treatment. BFB patients
      showed better clinical recovery and minor synkinesis than KT patients.
      CONCLUSIONS: BFB/EMG seems to be more useful than KT in Bell's palsy treatment.
      This could be due to the fact that BFB/EMG gives more accurate information than
      KT on muscle activation with better modulation in voluntary recruitment of motor
      unit.

PMID- 16096234
TI  - Effects of patient--clinician disagreement in occupational low back pain: a pilot
      study.
AB  - PURPOSE: To determine (1) patient--physical therapist and patient--physician
      agreement on clinical management of LBP, (2) patient perception of agreement
      between physical therapist and physician, (3) association between agreement and
      outcome (return to work, self-perceived disability). METHOD: Thirty-five workers
      compensated for LBP responded to a telephone interview within 1 week of referral
      to physical therapy. They were asked about agreement with the physical therapist
      and the physician regarding the clinical management of their LBP and whether they
      thought the physical therapist was providing the treatment the physician would
      have thought appropriate. They completed a second interview upon returning to
      work or after 3 months. They answered questionnaires on self-perceived
      disability, psychological distress, coping strategies, and job satisfaction at
      both baseline and follow-up. RESULTS: Nearly all patients (97.1%) agreed with the
      physical therapist and all believed the physical therapist was providing the
      treatment the physician would have thought appropriate. The 10 (28.6%) patients
      who disagreed with their physician on medical management of their LBP were less
      satisfied with the medical care (P=0.05), technical quality of the visit
      (P=0.01), and catastrophized more about their pain (P=0.03) than those who
      agreed. Disagreement was not associated with greater time off-work or greater
      self-perceived disability. CONCLUSION: Patients who disagreed with their
      physician were less satisfied with their medical management, and catastrophized
      more about their pain than those who agreed, but disagreement was not associated
      with chronicity or disability. Studies with larger sample sizes should
      investigate the role of other factors, such as patient expectations, in the
      transition to chronicity.

PMID- 16096235
TI  - Disability management practices in Ontario workplaces: employees' perceptions.
AB  - PURPOSE: The purpose of this study was to obtain employees' perceptions about
      disability management (DM) at their workplaces. METHODS: Data were obtained from
      focus group interviews and individual telephone interviews with 58 employees who
      had sustained a work-related injury or disability in Ontario, Canada.
      Participants also completed a 22-item Organizational Policies and Practices (OPP)
      Questionnaire that asked questions about workplace DM practices. RESULTS:
      Respondents emphasized the need for job accommodation, the importance of open and
      clear communication and the necessity of job retraining. The provision of
      ergonomic modifications to their worksites and the development of meaningful and
      specific DM policies and procedures were seen as key to a comprehensive workplace
      DM program. Education about health and safety also was identified as an important
      component of creating a supportive workplace environment. The OPP questionnaire
      showed good internal consistency (Cronbach's alpha=0.95) and discriminant
      validity. CONCLUSION: This study demonstrates the importance of workplaces
      communicating with their employees and respecting their opinions when
      establishing and carrying out DM policies and practices. The OPP Questionnaire is
      useful in determining how DM is managed in the workplace.

PMID- 16096236
TI  - Health promotion needs of physically disabled individuals with lower limb
      amputation in Rwanda.
AB  - PURPOSE: The objectives of the study were to identify the health-related
      behaviors among physically disabled individuals with lower limb amputation
      resident in Rwanda, the factors that influenced these behaviors, and the major
      issues that should be targeted in health promotion programs for physically
      disabled individuals with lower limb amputation. METHOD: A cross-sectional
      survey, utilizing a self-administered questionnaire, was carried out among 334
      lower limb amputees who volunteered to take part in the study. In addition, a sub
      sample of 15 participants was purposely selected for in-depth face-to-face
      interviews. RESULTS: Many participants did not engage in physical exercises
      (64.7%). Others abused alcohol on daily basis (14.4%), smoked 11-20 cigarettes
      daily (13.2%), and used recreational drugs such as marijuana, opium and cocaine
      (9.6%). There were significant associations between the age group of the
      participants and participation in exercises (P=0.001), and consuming alcohol,
      tobacco and recreational drugs (P=0.001). In-depth interviews revealed factors
      influencing the behavior of participants. CONCLUSIONS: Participants were found to
      be at risk of secondary complications because of poor lifestyle choices. There is
      a need to develop and promote wellness-enhancing behaviors in order to enhance
      the health status of physically disabled individuals in Rwanda who have lower
      limb amputations.

PMID- 16096237
TI  - The use and impact of assistive devices and other environmental modifications on
      everyday activities and care in young children with cerebral palsy.
AB  - PURPOSE: The study describes use of assistive devices and other environmental
      modifications, and their impact on everyday activities and care in young children
      with cerebral palsy (CP). METHOD: Ninety-five children (55 boys, 40 girls; mean
      age 58 months, SD 18 months) and their parents were studied using a cross
      sectional design. The Pediatric Evaluation of Disability Inventory (PEDI) was
      applied to assess daily activities using the three measurement scales: functional
      skills, caregiver assistance, and modifications of the environment. Use of
      modifications was described related to the five severity levels of the Gross
      Motor Function Classifications System (GMFCS). Impact was rated on the Caregiver
      Assistance scale of the PEDI and on a five-point Likert scale. RESULTS: Out of
      the 1075 provided environmental modifications, 980 were in regular use to support
      mobility, self-care and social function among 84 children. The number increased
      with GMFCS levels; children at levels IV and V used 80% of the modifications,
      with large variations between the children at same level. Adaptations of housing
      and transportation facilitated effective use of assistive devices. Half of the
      parents rated the modifications to have moderate to very large effect on the
      child's mobility, 25% on self-care skills, and 20% on social function.
      Furthermore, 65% reported that the modifications lightened the caregiving for
      mobility, 75% for self-care and 25% for social function. Functional independence
      and care demands often benefited from different types of modifications.
      CONCLUSION: The variations in use and benefits of environmental modifications
      indicate need of comprehensive assistive technology assessments, including child
      factors, family factors, technology factors and service system factors.

PMID- 16096238
TI  - Use of healthcare a long time after severe burn injury; relation to perceived
      health and personality characteristics.
AB  - PURPOSE: The aim of the study was to evaluate which factors are associated with
      the use of healthcare a long time after severe burn injury. METHOD: After a
      review process based on clinical reasoning, 69 former burn patients out of a
      consecutive group treated at the Uppsala Burn Unit from 1980--1995 were visited
      in their homes and their use of care and support was assessed in a semi
      structured interview. Post-burn health was assessed with the Burn-Specific Health
      Scale-Brief (BSHS-B) and personality was assessed with the Swedish universities
      Scales of Personality (SSP). RESULTS: The participants were injured on average
      eight years previously. Thirty-four had current contact with healthcare due to
      their burn injury and had significantly lower scores on three BSHS-B-domains:
      Simple Abilities, Work and Hand function, and significantly higher scores for the
      SSP-domain Neuroticism and the SSP-scales Stress Susceptibility, Lack of
      Assertiveness, and lower scores for Social Desirability. There was no relation to
      age, gender, time since injury, length of stay, or to the surface area burned.
      CONCLUSIONS: A routine screening of personality traits as a supplement to long
      term follow-ups may help in identifying the patient's need for care.

PMID- 16096239
TI  - The influence of functional limitations and various demographic factors on self
      reported activity restriction at older ages.
AB  - PURPOSE: The study analysed some differentials in self-reported restrictions for
      personal care activities. Activity restrictions are the result of basic
      functional limitations (vision, mobility...), but such limitations do not evenly
      reduce activity performance. We assessed how age, sex and the place of residence
      (household or institutions) changed the risk of reporting restrictions for
      similar functional problems. METHOD: We used the French disability survey data on
      personal care activity restrictions and functional limitations (physical, visual,
      time orientation) for people aged 55 years and older (n=16961). A logistic
      regression model shows the separate impact of the nature of functional
      limitations and of age, gender and residence on the risk of reported
      restrictions. RESULTS: Half of the people aged 55 and older reported functional
      problems; 20% of them also reported personal care activity restrictions. The
      probability of reporting restrictions was higher for people with several types of
      limitations, especially orientation and physical controlling for such
      limitations, the probability of restriction increased with age beyond 70, was
      higher for men than women below 70, and was higher in institutions than in
      households. CONCLUSION: Self-reported activity restrictions are not solely
      related to functional limitations but also to various demographic variables
      likely to modify the impact of these limitations on activity performance. These
      findings suggest studying differentials in the resources allowing to compensate
      limitations and to prevent reported restrictions.

PMID- 16096240
TI  - Outcomes in patients admitted for rehabilitation with spinal cord or cauda equina
      lesions following degenerative spinal stenosis.
AB  - PURPOSE: To evaluate outcome measures and the factors affecting them in patients
      treated between 1962 and 2000 at Loewenstein Rehabilitation Hospital, Israel.
      METHOD: This retrospective cohort study included 262 patients with spinal
      neurological lesions (spinal cord or cauda equina lesions) following degenerative
      spinal stenosis. Data were collected retrospectively. Survival was assessed using
      the Kaplan-Meier method and the relative mortality risk by the Cox model.
      Neurological recovery was evaluated by the change in Frankel grades, and factors
      that affect it were assessed by logistic regression. Associations of length of
      stay in rehabilitation were analyzed with ANOVA. RESULTS: Median age at lesion
      onset was 61 years and median survival 17.6 years. Age at spinal neurological
      lesion onset was found to be the only factor with a significant effect on
      survival. Of the 148 patients who had Frankel grades A, B, or C on admission, 58%
      achieved recovery to grades D and E. Frankel grade at admission, age, and spinal
      neurological level had a significant effect on recovery. The mean length of stay
      was 99.7 days, and only Frankel grade had a significant effect on length of stay.
      CONCLUSIONS: Patients with spinal stenosis and disabling spinal neurological
      lesions can achieve significant neurological recovery and survive for many years.
      They require adequate care in a specialist rehabilitation system.

PMID- 16096241
TI  - Vocational training integrated into inpatient psychosomatic rehabilitation--short
      and long-term results from a controlled study.
AB  - PURPOSE: The aim of this study was to determine the impact of a vocational
      training programme on short- and long-term results after psychosomatic
      rehabilitation. METHOD: 1,590 inpatients were screened for vocational
      integration. A high-risk group of 266 patients was randomly assigned to the
      vocational training programme plus psychosomatic treatment; treatment- as- usual
      served as a control condition. An occupational training was conducted at local
      companies, closely integrated into psychosomatic treatment. Vocational attitudes
      and adjustment were studied at intake, discharge, three, 12 and 24 month follow
      ups. RESULTS: More than half of the study participants were unemployment and/or
      long-term work-disabled harbouring strong negative attitudes toward return to
      work. Forty-six percent of the intervention group declined from participation,
      but complied with follow-up investigation. At discharge, participants of the
      vocational training programme had become more optimistic regarding resuming work.
      One year following discharge, participants of the training programme reported
      less absence from work. After 24 months, vocational adjustment had improved
      considerably among programme participants, and declined among controls and
      refusers. CONCLUSION: An intensive vocational training programme is effective in
      promoting positive attitudes to work, reducing work disability and promoting
      return-to-work. However, a randomized design may be not optimal; evaluation
      necessitates long-term follow-up.

PMID- 16096242
TI  - An organizational perspective on goal setting in community-based brain injury
      rehabilitation.
AB  - PURPOSE: To use a taxonomy of goal content, developed in community-based brain
      injury rehabilitation to examine and compare the content of goals set within two
      different service settings; and to further examine the potential of the taxonomy
      to be a reliable and comprehensive framework for classifying goals. METHOD:
      Qualitative analysis and categorization of 1492 goal statements extracted from a
      community-based brain injury rehabilitation service over two time periods (1996-
      97, 1998--99), and cross-organizational comparison of ratings of goal
      classifications using a random sample of 100 goal statements drawn from this data
      set and the original 1765 goal statements used in developing the taxonomy.
      RESULTS: Application of the taxonomy beyond the original service setting in which
      it was developed indicated a strong inter-rater reliability, with a high test
      retest agreement reported over time. For both services, a small number of
      categories accounted for a substantial proportion of goals set within the two
      time periods, while considerable change was evident in goals between the two
      periods for one service. Further, both placed emphasis on individually focused
      goals rather than relationship or family-related goals. CONCLUSION: The taxonomy
      provides a reliable means for classifying goals and is a useful tool for
      exploration of the multiple influences on goal setting. Further application of
      the taxonomy to examine the relative influence on goal setting of client factors
      versus a range of organizational factors would be beneficial.

PMID- 16096243
TI  - Psychological comorbidity in medical rehabilitation--the need for education.
AB  - PURPOSE: Prevalence of comorbid mental disorders in rehabilitation patients is
      high. In spite of the bio-psycho-social approach in rehabilitation, recognition
      and treatment rates of comorbid mental disorders during rehabilitation are low.
      The purpose of the study was to raise specific information about current clinical
      practice concerning comorbid mental disorders and training needs of
      rehabilitation personnel. METHOD: 435 questionnaires were sent out to medical
      personnel in 54 rehabilitation hospitals in south-west Germany. RESULTS:
      Psychologists in rehabilitation spend most of their time on counselling (45%) and
      group interventions (29%). Physicians and psychologists both feel highly
      responsible for recognizing mental disorders and motivating patients to seek
      aftercare. Screeners are rarely used by psychologists and physicians. Seventy-six
      percent of the participants would take part in specific training sessions. High
      training needs were stated for affective, anxiety and somatoform disorders. A
      specific training session for mental health in rehabilitation should last at
      least half a day and cover affective, anxiety and somatoform disorders.
      CONCLUSIONS: Taking these results into account, it is possible to put together a
      training program in diagnostics of comorbid mental disorders, which fits the
      needs of the professionals.

PMID- 16096244
TI  - Foot and leg problems are important determinants of functional status in
      community dwelling older people.
AB  - PURPOSE: To determine whether foot and leg problems are independently associated
      with functional status in a community sample of older people after adjusting for
      the influence of socio-demographic, physical and medical factors. METHOD: Data
      were analysed from the Health Status of Older People project, a population-based
      study involving a random sample of 1000 community-dwelling people aged 65 - 94
      years (533 females, 467 males, mean age 73.4 years +/- 5.87). A structured
      interview and brief physical examination were used to investigate the
      associations between self-reported foot and leg problems and functional status.
      Functional status was assessed using: (i) timed 'Up & Go' test, (ii) self
      reported difficulty climbing stairs, (iii) self-reported difficulty walking one
      kilometer, (iv) self-reported difficulty performing instrumental activities of
      daily living (IADLs), and (v) self-reported history of one or more falls in the
      previous 12 months. These associations were then explored after adjusting for
      socio-demographic, physical and medical factors. RESULTS: Thirty-six percent of
      the sample reported having foot or leg problems. Univariate analyses revealed
      that people with foot and leg problems were significantly more likely to exhibit
      poorer functional status in all parameters measured. After adjusting for socio
      demographic, physical and medical factors, foot and leg problems remained
      significantly associated with impaired timed 'Up & Go' performance (OR = 2.15,
      95%CI 1.55 - 2.97), difficulty climbing stairs (OR = 3.33, 95%CI 1.98 - 5.61),
      difficulty walking one kilometer (OR = 3.13, 95%CI 2.09 - 4.69), and history of
      falling (OR = 1.73, 95%CI 1.26 - 2.37). CONCLUSIONS: Foot and leg problems are
      reported by one in three community-dwelling people aged 65 years and older.
      Independent of the influence of age, gender, common medical conditions and other
      socio-demographic factors, foot and leg problems have a significant impact on the
      ability to perform functional tasks integral to independent living.

PMID- 16096245
TI  - Locus of control and regional differences in sickness absence in Sweden.
AB  - PURPOSE: The aim of this study was to investigate if there are differences in
      locus of control (LOC), at a societal level, between two residential areas in
      Sweden with substantial differences in sickness absence. METHOD: A postal
      questionnaire was sent to 1500 randomly selected men and women aged 20 - 64
      years. Five hundred questionnaires were sent to people living in Stromsund (a
      sparsely populated municipality in northern Sweden with high rates of sickness
      absence) and 1000 questionnaires to people in the Swedish capital of Stockholm,
      which has a low rate of sickness absence. RESULTS AND CONCLUSION: A comparison of
      LOC in the two study areas supported our hypothesis to a certain extent, external
      locus being more prominent in Stromsund. When physical and mental health and
      income were considered, however, the differences disappeared. Consequently, this
      study did not support the opinion that differences in sickness absence can be
      explained by LOC at a societal level.

PMID- 16096246
TI  - A randomized trial comparing a group exercise programme for back pain patients
      with individual physiotherapy in a severely deprived area.
AB  - PURPOSE: To compare a group exercise programme known as the Back to Fitness
      programme with individual physiotherapy for patients with non-specific low back
      pain from a materially deprived area. METHOD: This was a randomized controlled
      trial including 237 physiotherapy patients with back pain lasting more than six
      weeks. Participants were allocated to either the Back to Fitness programme or to
      individual physiotherapy, and followed up at three months and 12 months after
      randomization. The main outcome measure was the Roland Disability Questionnaire.
      Secondary measures were: SF12, EQ5D, Pain Self-Efficacy Scale. Health care
      diaries recording patients' use of health care resources were also collected over
      a 12-month period. RESULTS: There were no statistically significant differences
      in change scores between groups on the primary outcome measure at three months
      (CI - 2.24 to 0.49) and at 12 months (CI - 1.68 to 1.39). Only minor improvements
      in disability scores were observed in the Back to Fitness group at three months
      and 12 months respectively (mean change scores; - 0.89, - 0.77) and in the
      individual physiotherapy arm (mean change scores; - 0.02, - 0.63). Further
      analysis showed that patients from the most severely deprived areas were
      marginally worse at three month follow-up whereas those from more affluent areas
      tended to improve (CI 0.43 to 3.15).

PMID- 16096247
TI  - Understanding and measuring powered wheelchair mobility and manoeuvrability. Part
      I. Reach in confined spaces.
AB  - PURPOSE: To determine: (1) what wheelchair manoeuvrability factors are important
      and (2) the effects of powered wheelchair design on the ability to reach in a
      confined space. METHOD: The relative importance of five aspects of wheelchair
      manoeuvrability was determined through a survey of users of wheelchairs (N = 52)
      and health care professionals and others (N = 89). A single young, non-disabled
      subject undertook repeated trials of reach distance on to a counter at the end of
      a corridor whose width could be adjusted by moving Styrofoam walls. RESULTS:
      Reaching, moving in confined spaces and avoiding collisions were more important
      than speed and avoiding the need to drive backwards. The rear wheel drive powered
      wheelchair was found to allow the greatest reach when driving backwards into the
      space and the wheelchair which moved in a sideways direction allowed greatest
      reach in the narrowest corridor. CONCLUSIONS: The survey concluded that
      manoeuvring in small spaces and reaching without collisions were important. The
      powered wheelchair with sideways capability afforded the greatest reach in
      confined spaces except when the rear wheel drive chair was driven in backwards.
      The survey respondents did not place a high priority on avoiding backwards
      driving but some people find this difficult to do safely.

PMID- 16096248
TI  - Adaptation of a seated postural control measure for adult wheelchair users.
AB  - PURPOSE: Clinical measures of seated postural control in adults are not
      standardized and most are derived from in-house tools. The purpose of this study
      is to adapt a pediatric instrument to evaluate seated postural control in adult
      wheelchair users. METHOD: The new instrument is called the Seated Postural
      Control Measure for Adults (SPCMA) 1.0. Five preliminary versions were pretested
      with some 20 adults by two raters and a group of experts. RESULTS: This
      instrument comprises three sections: Section 1, level of sitting scale for adults
      (1 item, 7-point ordinal scale); Section 2, static postural alignment (22 items,
      7-point ordinal scale); and Section 3, postural alignment after a dynamic
      activity, propulsion of the wheelchair on flat terrain and an incline (22 items,
      7-point ordinal scale). CONCLUSIONS: The SPCMA for Adults 1.0 improves the
      quality and uniformity of evaluations done by different raters, which facilitates
      more rigorous follow-up of clients over time, communication between
      professionals, and objective verification of the attainment of intervention
      objectives.

PMID- 16096249
TI  - Perceived images of disability: the reflections of two undergraduate medical
      students in a university in South Africa on life in a wheelchair.
AB  - PURPOSE: The purpose of this manuscript is to document the experiences of two
      undergraduate medical students at the University of Cape Town, South Africa, who
      registered for a 4-week special study module titled "Images of Disability", as
      part of the medical training programme. The objective of the module was to foster
      the development of positive attitudes toward persons with physical disability
      through role-playing. METHOD: The special study module required that the students
      assumed they had mobility impairments and were physically confined to
      wheelchairs. The students were required to document their personal experiences of
      life in a wheelchair for five consecutive working days. RESULTS: The students had
      to deal with their perceptions of the attitudes of individuals they interacted
      with, which resulted in feeling of inferiority and lowered self-esteem. The
      students also identified obstacles in the environment which hindered integration.
      CONCLUSIONS: The students reported significant positive changes in their
      attitudes towards persons with disabilities.

PMID- 16096250
TI  - Development and reliability of the Motivation for Change Questionnaire.
AB  - PURPOSE: The purpose of this study was to describe the development of the
      Motivation for Change Questionnaire (MCQ) and to test its intra-patient
      reliability on musculoskeletal pain patients in interdisciplinary rehabilitation
      as a basis for use in rehabilitation planning. METHOD: The MCQ questionnaire was
      developed from a literature search in the Medline, Cinahl and Psychlit databases
      concerning motivating factors for change in the life and work situation.
      Questions covering these factors were developed (item generation). Factor
      analysis of the questions implied a reduction of the number of questions (item
      reduction). Inter-item correlation was assessed on the baseline administration of
      the questionnaire by calculating Cronbach's alpha. When testing the structure of
      the scales, it was shown that the MCQ questionnaire could be described in two
      scales, one scale relating to motivation for change in the life situation and the
      other focusing on motivation for change in the work situation and in total 49
      questions. RESULTS: The test -- retest reliability was calculated using the intra
      class correlation coefficient (ICC) and 95% confidence intervals were calculated.
      One question was excluded due to the threshold limit of > 0.5. Seven scales
      relating to the life situation were accepted by the analysis: social support,
      mastery in life, challenges in life, control in life, values, self-efficacy and
      self-confidence. Six scales relating to the work situation were also accepted: co
      worker support, supervisory support, challenges in work, job control, interaction
      and job-satisfaction. CONCLUSIONS: The MCQ questionnaire with 48 questions is
      reliable for use on musculoskeletal pain patients in interdisciplinary
      rehabilitation. It can be used to identify each individual's motivating factors
      for change in life and work situation as a basis for motivational work within
      rehabilitation and/or to measure within-subject changes in motivation over time.
      The validity and the responsiveness of the MCQ, need to be studied.

PMID- 16096251
TI  - Reliability in assigning ICF codes to children with special health care needs
      using a developmentally structured interview.
AB  - PURPOSE: The purpose of this study was to determine if two teams of raters could
      reliably assign codes and performance qualifiers from the Activities and
      Participation component of the International Classification of Functioning,
      Disability, and Health (ICF) to children with special health care needs based on
      the results of a developmentally structured interview. METHOD: Children (N = 40),
      ages 11 months to 12 years 10 months, with a range of health conditions, were
      evaluated using a structured interview consisting of open-ended questions and
      scored using developmental guidelines. For each child, two raters made a binary
      decision indicating whether codes represented an area of need or no need for that
      child. Raters assigned a performance qualifier, based on the ICF guidelines, to
      each code designated as an area of need. Cohen's kappa statistic was used as the
      measure of inter-rater reliability. RESULTS: Team I reached good to excellent
      agreement on 39/39 codes and Team II on 38/39 codes. Team I reached good to
      excellent agreement on 5/5 qualifiers and Team II on 10/14 qualifiers.
      CONCLUSIONS: A developmentally structured interview was an effective clinical
      tool for assigning ICF codes to children with special health care needs. The
      interview resulted in higher rates of agreement than did results from
      standardized functional assessments. Guidelines for assigning performance
      qualifiers must be modified for use with children.

PMID- 16096252
TI  - The positive impact of multiple sclerosis (MS) on carers: associations between
      carer benefit finding and positive and negative adjustment domains.
AB  - PURPOSE: This study examined benefit finding in MS carers including the
      dimensionality of benefit finding, relations between carer and care recipient
      benefit finding, and the effects of carer benefit finding on carer positive and
      negative adjustment domains. METHOD: A total of 267 carers and their care
      recipients completed questionnaires at Time 1 and 3 months later, Time 2 (n =
      155). Illness data were collected at Time 1, and number of problems, stress
      appraisal, benefit finding, negative (global distress, negative affect) and
      positive (life satisfaction, positive affect, dyadic adjustment) adjustment
      domains were measured at Time 2. RESULTS: Qualitative data revealed seven benefit
      finding themes, two of which were adequately represented by the Benefit Finding
      Scale (BFS). Factor analyses indicated two factors (Personal Growth, Family
      Relations Growth) which were psychometrically sound and showed differential
      relations with illness and adjustment domains. Although care recipients reported
      higher levels of benefit finding than carers, their benefit finding reports
      regarding personal growth were correlated. The carer BFS factors were positively
      related to carer and care recipient dyadic adjustment. Care recipient benefit
      finding was unrelated to carer adjustment domains. After controlling for the
      effects of demographics, care recipient characteristics, problems and appraisal,
      carer benefit finding was related to carer positive adjustment domains and
      unrelated to carer negative adjustment domains. CONCLUSION: Findings support the
      role of benefit finding in sustaining positive psychological states and the
      communal search for meaning within carer -- care recipient dyads.

PMID- 16096253
TI  - Comparing self-report, clinical examination and functional testing in the
      assessment of work-related limitations in patients with chronic low back pain.
AB  - PURPOSE: To compare the work-related limitations assessed using self-report,
      clinical examination and functional testing in patients with chronic low back
      pain (CLBP). METHODS: Work-related limitations of 92 patients were assessed using
      self-report, clinical examination and functional testing. To obtain the assessed
      limitations the patient (self-report), the physician (clinical examination) and a
      trained evaluator (functional testing) completed a scorings form about the work
      related limitations of the patient. The Isernhagen Work Systems Functional
      Capacity Evaluation (IWS FCE) was used to obtain the functional testing results.
      A kappa value of more than 0.60, absolute agreement of more than 80% and ICC of
      more than 0.75 were considered as acceptable. RESULTS: Little agreement and
      correlation among self-report, clinical examination and functional testing were
      found for the assessment of work-related limitations. Self-reported limitations
      were considerably higher than from those derived from clinical examination or
      functional testing. Additionally, the limitations derived from the clinical
      examination were higher than those derived from the IWS FCE. CONCLUSION:
      Comparing self-report, clinical examination and functional testing for assessing
      work-related limitations in CLBP patients showed large considerable differences
      in limitations. Professional health care workers should be aware of these
      differences when using them in daily practice.

PMID- 16096254
TI  - Functional performance and quality of life related to training and detraining of
      community-dwelling elderly.
AB  - PURPOSE: Despite clear evidence of physiological declines during detraining, the
      effects of detraining on functional performance and quality of life have not
      often been investigated. The purpose of this study was to investigate functional
      performance and quality of life measures after a training and detraining
      programme with community-dwelling elderly. METHOD: Twenty-three subjects took
      part in a combined programme of muscle strengthening and aerobic conditioning
      twice a week and were assessed at baseline, after training, and after one, two,
      and three months of detraining. Functional performance was assessed by gait speed
      and by the rate of ascending and descending stairs, while quality of life was
      evaluated by the Nottingham Health Profile. RESULTS: Repeated measures ANOVA
      showed that gains observed in measures of gait speed, ascending, and descending
      stairs returned to baseline after one, two, and three months of detraining,
      respectively. However, the gains in quality of life remained unchanged.
      CONCLUSIONS: One-month detraining was enough to show functional decline, with
      gait speed the most sensitive parameter to detect these changes and QL measure
      most resilient, beneficial factor during the detraining process. Based on these
      findings, it is recommended that programmes devised for elderly should not be
      interrupted, to maintain the acquired benefits.

PMID- 16096255
TI  - Women's perception of changes in the social network after a spinal cord injury.
AB  - PURPOSE: To describe how women with a spinal cord injury (SCI) perceived changes
      in the social network, and how these changes affected their ability to
      participate in occupation. METHOD: Thirteen women, aged 25 to 61 years, with a
      SCI were interviewed twice. The interviews focused on their ability to
      participate in occupation, their relations with individuals within the social
      network, and changes in the social network following the SCI. The analysis was
      carried out using qualitative content analysis. RESULTS: The women described an
      emotional need for social support after the SCI to participate in occupation.
      This was a new experience that required time to adapt to. The women also
      described a need for practical social support from the social network members to
      manage meaningful occupation. After the SCI, the women had developed new habits
      through close cooperation with members in the social network. The women felt that
      they had become more responsible for the development of their relations. Many
      relations had improved after the SCI, while some had decreased. The women had
      also developed new relations with other persons with disabilities. CONCLUSIONS:
      The women perceived substantial changes in the social network following the SCI,
      which in several ways affected their ability to participate in occupation. To
      adapt to their new life situation, the women gradually developed different
      strategies. The results point out the need to identify persons in the social
      network that women with SCI develop relations with, and integrate them in the
      rehabilitation process.

PMID- 16096256
TI  - Discriminant ability of the Trunk Impairment Scale: A comparison between stroke
      patients and healthy individuals.
AB  - PURPOSE: The Trunk Impairment Scale (TIS) is a standardized scale to evaluate the
      trunk function in stroke patients. It was the aim of this study to determine the
      discriminant ability of the TIS by comparing stroke patients with healthy
      individuals. Further, the variables that had an influence on obtaining a high
      score on the TIS in healthy subjects were examined. METHOD: Forty stroke patients
      and 40 age- and sex-matched healthy individuals were included in the study. TIS
      scores from the stroke patients and healthy individuals were compared using the
      Wilcoxon ranked sum test. RESULTS: Sub-scale and total TIS scores showed
      significant differences between stroke patients and healthy individuals (P <
      0.0001). Univariate analysis and logistic regression analysis further revealed
      that younger persons, women and people who are more active in daily life have a
      higher chance of obtaining a high score on the TIS. CONCLUSIONS: The TIS
      discriminates between stroke patients and healthy individuals. A submaximal score
      on the TIS was found in 45% of the healthy subjects suggesting that a lower score
      on the TIS still indicates normal trunk function and full participation in daily
      life.

PMID- 16096257
TI  - Evaluation of the driving ability in disabled persons: a practitioners' view.
AB  - PURPOSE AND METHODS: The purpose of this paper is to present, on the basis of
      four genuine cases from the Rehabilitation Research Unit of Oulu University, the
      theoretical frame in which evaluations of driving ability of disabled persons can
      be made. RESULTS: First, it is not the operations with the control devices but
      the correct mental actions which the driver carries out with the help of the
      control devices which are crucial for safe driving. Second, driving ability is
      only partly a biomedical object of research and one ought to avoid an excessive
      medicalisation of an evaluation of driving ability. Third, the driver meets
      traffic situations not by his or her separate biological or psychological
      functions, such as vision, attention, memory, thinking, motives, but as an
      integrated whole, as a personality. CONCLUSIONS: By its complexity an evaluation
      of driving ability can be compared to an evaluation of working capacity where
      often a multidisciplinary team is needed. When evaluating driving ability we have
      to take a step from low-level motor operations towards high-level mental actions,
      from the measurement of acuity of eyesight towards the testing of the flexibility
      of perception, from the diagnosis-based evaluation to the patient-based
      evaluation, from using the common pencil-paper tests towards the traffic-related
      task-specific tests and from the testing of separate single general non-driving
      related factors towards an evaluation of the theoretically based driving
      performance as whole.

PMID- 16096259
TI  - The alpha7 nicotinic acetylcholine receptor: molecular modelling, electrostatics,
      and energetics.
AB  - The structure of a homopentameric alpha7 nicotinic acetylcholine receptor is
      modelled by combining structural information from two sources: the X-ray
      structure of a water soluble acetylcholine binding protein from Lymnea stagnalis,
      and the electron microscopy derived structure of the transmembrane domain of the
      Torpedo nicotinic receptor. The alpha7 nicotinic receptor model is generated by
      simultaneously optimising: (i) chain connectivity, (ii) avoidance of
      stereochemically unfavourable contacts, and (iii) contact between the beta1-beta2
      and M2-M3 loops that have been suggested to be involved in transmission of
      conformational change between the extracellular and transmembrane domains. A
      Gaussian network model was used to predict patterns of residue mobility in the
      alpha7 model. The results of these calculations suggested a flexibility gradient
      along the transmembrane domain, with the extracellular end of the domain more
      flexible that the intracellular end. Poisson-Boltzmann (PB) energy calculations
      and atomistic (molecular dynamics) simulations were used to estimate the free
      energy profile of a Na+ ion as a function of position along the axis of the pore
      lining M2 helix bundle of the transmembrane domain. Both types of calculation
      suggested a significant energy barrier to exist in the centre of the (closed)
      pore, consistent with a "hydrophobic gating" model. Estimations of the PB energy
      profile as a function of ionic strength suggest a role of the extracellular
      domain in determining the cation selectivity of the alpha7 nicotinic receptor.
      These studies illustrate how molecular models of members of the nicotinic
      receptor superfamily of channels may be used to study structure-function
      relationships.

PMID- 16096260
TI  - Prothymosin alpha-receptor associates with lipid rafts in PHA-stimulated
      lymphocytes.
AB  - Lipid rafts are specialized plasma membrane microdomains in which
      glycosphingolipids and cholesterol are major structural components. Their
      relative insolubility to nonionic detergents is the most widely used method to
      purify these structures. Several signalling proteins are associated with these
      microdomains in T lymphocytes, including receptors for growth factors and
      cytokines. ProTalpha is a highly conserved and widely distributed protein whose
      physiological functions remain elusive. In previous works we identified, by means
      of affinity cross-linking, affinity chromatography and fluorescence microscopy, a
      set of binding proteins for ProTalpha in human lymphoblasts. Now, this work goes
      deeply in that ProTalpha receptor description revealing, by different
      experimental approaches, its presence in lipid rafts. Moreover, our results fit a
      model in which a tyrosine phosphorylation signalling cascade confined to rafts is
      initiated upon ProTalpha receptor recognition, which represents an important and
      promising finding in the research for elucidating the molecular mechanisms
      underlying the immunomodulatory functions of ProTalpha.

PMID- 16096261
TI  - Sequence and hydropathy profile analysis of two classes of secondary
      transporters.
AB  - A structural class in the MemGen classification of membrane proteins is a set of
      evolutionary related proteins sharing a similar global fold. A structural class
      contains both closely related pairs of proteins for which homology is clear from
      sequence comparison and very distantly related pairs, for which it is not
      possible to establish homology based on sequence similarity alone. In the latter
      case the evolutionary link is based on hydropathy profile analysis. Here, we use
      these evolutionary related sets of proteins to analyze the relationship between E
      values in BLAST searches, sequence similarities in multiple sequence alignments
      and structural similarities in hydropathy profile analyses. Two structural
      classes of secondary transporters termed ST[3], which includes the Ion
      Transporter (IT) superfamily and ST[4], which includes the DAACS family (TC#
      2.A.23) were extracted from the NCBI protein database. ST[3] contains 2051 unique
      sequences distributed over 32 families and 59 subfamilies. ST[4] is a smaller
      class containing 399 unique sequences distributed over 2 families and 7
      subfamilies. One subfamily in ST[4] contains a new class of binding protein
      dependent secondary transporters. Comparison of the averaged hydropathy profiles
      of the subfamilies in ST[3] and ST[4] revealed that the two classes represent
      different folds. Divergence of the sequences in ST[4] is much smaller than
      observed in ST[3], suggesting different constraints on the proteins during
      evolution. Analysis of the correlation between the evolutionary relationship of
      pairs of proteins in a class and the BLAST E-value revealed that: (i) the BLAST
      algorithm is unable to pick up the majority of the links between proteins in
      structural class ST[3], (ii) "low complexity filtering" and "composition based
      statistics" improve the specificity, but strongly reduce the sensitivity of BLAST
      searches for distantly related proteins, indicating that these filters are too
      stringent for the proteins analyzed, and (iii) the E-value cut-off, which may be
      used to evaluate evolutionary significance of a hit in a BLAST search is very
      different for the two structural classes of membrane proteins.

PMID- 16096262
TI  - Solution structure of the fifth and sixth transmembrane segments of the
      mitochondrial oxoglutarate carrier.
AB  - The structures of the fifth and sixth transmembrane segments of the bovine
      mitochondrial oxoglutarate carrier (OGC) and of the hydrophilic loop that
      connects them were studied by CD and NMR spectroscopies. Peptides F215-R246, W279
      K305 and P257-L278 were synthesized and structurally characterized. CD data
      showed that at high concentrations of TFE and SDS all peptides assume alpha
      helical structures. (1)H-NMR spectra of the three peptides in TFE/water were
      fully assigned and the secondary structures of the peptides were obtained from
      nuclear Overhauser effects, (3)J(aH-NH) coupling constants and alphaH chemical
      shifts. The three-dimensional solution structures of the peptides were generated
      by distance geometry calculations. A well-defined alpha-helix was found in the
      region L220-V243 of peptide F215-R246 (TMS-V), in the region P284-M303 of peptide
      W279-K305 (TMS-VI) and in the region N261-F275 of peptide P257-L278 (hydrophilic
      loop). The helix L220-V243 exhibited a sharp kink at P239, while a little bend
      around P291 was observed in the helical region P284-M303. Fluorescence studies
      performed on peptide W279-K305, alone and together with other transmembrane
      segments of OGC, showed that the W279 fluorescence was quenched upon addition of
      peptide F215-R246, but not of peptides K21-K46, R78-R108 and P117-A149 suggesting
      a specific interaction between TMS-V and TMS-VI of OGC.

PMID- 16096263
TI  - Membrane integration and topology of the first transmembrane segment in normal
      and Southeast Asian ovalocytosis human erythrocyte anion exchanger 1.
AB  - Anion exchanger 1 (AE1, or Band 3) is an integral membrane glycoprotein found in
      erythrocytes, responsible for the electroneutral exchange of chloride and
      bicarbonate ions across the plasma membrane. Southeast Asian ovalocytosis (SAO)
      results from a nine-amino acid deletion in the first transmembrane segment (TM)
      of the AE1 protein that abolishes its transport function. The effects of the SAO
      deletion on: (1) the efficiency of integration of TM1 into the membrane, and (2)
      the precise positioning of TM1 relative to the membrane were investigated using
      scanning N-glycosylation mutagenesis in a cell-free transcription/translation
      system and in transfected HEK293 cells. AE1 or SAO constructs containing either
      the endogenous N-glycosylation site at Asn642 in extracellular loop 4 (EC4) or
      single N-glycosylation sites engineered into an expanded extracellular loop 1
      (EC1) were used. N-glycosylation efficiency of EC1 in the SAO construct was
      significantly lower than that of the AE1 construct, indicating that the SAO
      deletion impairs membrane integration of TM1 and the translocation of EC1 across
      the membrane. Scanning N-glycosylation mapping of EC1 in the cell-free system and
      in transfected cells showed that the C-terminus of both AE1 and SAO TM1 were at
      the same position relative to the membrane. Thus, the SAO deletion is likely to
      cause a pulling-in of the polar amino acid sequence immediately N-terminal to the
      deletion into the lipid bilayer, allowing SAO TM1 that was inserted to assume a
      transmembrane disposition.

PMID- 16096264
TI  - Substrate preference is altered by mutations in the fifth transmembrane domain of
      Ptr2p, the di/tri-peptide transporter of Saccharomyces cerevisiae.
AB  - The integral membrane protein Ptr2p transports di/tri-peptides into the yeast
      Saccharomyces cerevisiae. The sequence FYXXINXG (FYING motif) in the 5th
      transmembrane domain (TM5) is invariably conserved among the members of the PTR
      (Peptide TRansport) family ranging from yeast to human. To test the role of TM5
      in Ptr2p function, Ala-scanning mutagenesis of the 22 residues comprising TM5 was
      completed. All mutated transporters, with the exception of the Y248A mutant, were
      expressed as determined by immunoblots. In peptide-dependent growth assays, ten
      mutants of the non-FYING residues grew as well as wild-type Ptr2p on all twelve
      different peptides tested. All of the FYING motif mutants, except the non
      expressed Y248A, plus seven other mutants in TM5 exhibited differential growth on
      peptides including Leu-Leu and Met-Met-Met indicating that these mutations
      conferred substrate preference. In assays measuring direct uptake of the
      radioactive peptides (3)H-Leu-Leu or (14)C-Met-Met-Met, the F, I and G mutants of
      the FYING motif did not demonstrate accumulation of these peptides over a ten
      minute interval. The mutation N252A of the FYING motif, along with L240A, M250A,
      and L258A, exhibited differential substrate preference for Met-Met-Met over Leu
      Leu. Other mutations (T239A, Q241A, N242A, M245A, and A260) resulted in
      preference for Leu-Leu over Met-Met-Met. These data demonstrate that TM5, in
      particular its conserved FYING motif, is involved in substrate preference of
      Ptr2p.

PMID- 16096265
TI  - Molecular adhesion development in a neural cell monolayer forming in an
      ultrasound trap.
AB  - A 2-dimensional aggregate of C6 neural cells was formed rapidly (within 30 s) in
      suspension in a recently developed 1.5 MHz ultrasound standing wave trap. A
      typical 1 mm diameter aggregate contained about 3,500 cells. Spreading of
      membrane occurred between the aggregated cells. The rate of spreading of the
      tangentially developing intercellular contact area was 0.19 microm/min. The form
      of the suspended aggregate changed from one of a hexagonal arrangement of cells
      to one of a cell-monolayer-like continuous sheet of mostly quadrilateral and
      pentagonal cells as in a cell monolayer on a solid substratum. A range of
      fluorescent indicators showed that the >99% viability of the cells did not change
      during 1 h exposures; therefore cell viability was not compromised during the
      monolayer development. The average integral intensities from stained actin
      filaments at the spreading cell-cell interfaces after 1, 8 and 30 min were 14, 25
      and 46 microm(2) respectively. The cells in this work progressed from physical
      aggregation, through molecular adhesion, to displaying the intracellular
      consequences of receptor interactions. The ability to form mechanically strong
      confluent monolayer structures that can be monitored in situ or harvested from
      the trap provides a technique with general potential for monitoring the
      synchronous development of cell responses to receptor-triggered adhesion.

PMID- 16096266
TI  - The cholesterol-complexing agent digitonin modulates ligand binding of the bovine
      hippocampal serotonin 1A receptor.
AB  - The serotonin(1A) (5-HT(1A)) receptor is an important member of the superfamily
      of seven transmembrane domain G-protein-coupled receptors. We have examined the
      modulatory role of cholesterol on the ligand binding of the bovine hippocampal 5
      HT(1A) receptor by cholesterol complexation in native membranes using digitonin.
      Complexation of cholesterol from bovine hippocampal membranes using digitonin
      results in a concentration-dependent reduction in specific binding of the agonist
      8-OH-DPAT and antagonist p-MPPF to 5-HT(1A) receptors. The corresponding changes
      in membrane order were monitored by analysis of fluorescence polarization data of
      the membrane depth-specific probes, DPH and TMA-DPH. Taken together, our results
      point out the important role of membrane cholesterol in maintaining the function
      of the 5-HT(1A) receptor. An important aspect of these results is that non
      availability of free cholesterol in the membrane due to complexation with
      digitonin rather than physical depletion is sufficient to significantly reduce
      the 5-HT(1A) receptor function. These results provide a comprehensive
      understanding of the effects of the sterol-complexing agent digitonin in
      particular, and the role of membrane cholesterol in general, on the 5-HT(1A)
      receptor function.

PMID- 16096267
TI  - Cloning and functional characterization of two bacterial members of the NAT/NCS2
      family in Escherichia coli.
AB  - The coding potential of the genome of E. coli K-12 includes YgfO and YicE, two
      members of the evolutionarily conserved NAT/NCS2 transporter family that are
      highly homologous to each other (45% residue identity) and closely related to
      UapA of Aspergillus nidulans, a most extensively studied microbial member of this
      family. YgfO and yicE were cloned from the genome, over-expressed
      extrachromosomally and assayed for uptake of [(3)H]xanthine and other
      nucleobases, in E. coli K-12, under conditions of negligible activity of the
      corresponding endogenous systems. Alternative, essentially equivalent functional
      versions of YgfO and YicE were engineered by C-terminal tagging with an epitope
      from the E. coli lactose permease and a biotin-acceptor domain from Klebsiella
      pneumoniae. Both YgfO and YicE were shown to be present in the plasma membrane of
      E. coli and function as specific, high-affinity transporters for xanthine (K(m)
      4.2-4.6 microM for YgfO, or 2.9-3.8 microM for YicE), in a proton motive force
      dependent manner; they display no detectable transport of uracil, hypoxanthine,
      or uric acid at external concentrations of up to 0.1 mM. Both YgfO and YicE are
      inefficient in recognizing uric acid or xanthine analogues modified at position 8
      of the purine ring (8-methylxanthine, 8-azaxanthine, oxypurinol, allopurinol),
      which distinguishes them from their fungal homologues UapA and Xut1.

PMID- 16096268
TI  - Comparative substrate recognition by bacterial and fungal purine transporters of
      the NAT/NCS2 family.
AB  - We compared the interactions of purines and purine analogues with representative
      fungal and bacterial members of the widespread Nucleobase-Ascorbate Transporter
      (NAT) family. These are: UapA, a well-studied xanthine-uric acid transporter of
      A. nidulans, Xut1, a novel transporter from C. albicans, described for the first
      time in this work, and YgfO, a recently characterized xanthine transporter from
      E. coli. Using transport inhibition experiments with 64 different purines and
      purine-related analogues, we describe a kinetic approach to build models on how
      NAT proteins interact with their substrates. UapA, Xut1 and YgfO appear to bind
      several substrates via interactions with both the pyrimidine and imidazol rings.
      Fungal homologues interact with the pyrimidine ring of xanthine and xanthine
      analogues via H-bonds, principally with N1-H and =O6, and to a lower extent with
      =O2. The E. coli homologue interacts principally with N3-H and =O2, and less
      strongly with N1-H and =O6. The basic interaction with the imidazol ring appears
      to be via a H-bond with N9. Interestingly, while all three homologues recognize
      xanthines with similar high affinities, interaction with uric acid or/and
      oxypurinol is transporter-specific. UapA recognizes uric acid with high affinity,
      principally via three H-bonds with =O2, =O6 and =O8. Xut1 has a 13-fold reduced
      affinity for uric acid, based on a different set of interactions involving =O8,
      and probably H atoms from positions N1, N3, N7 or N9. YgfO does not recognize
      uric acid at all. Both Xut1 and UapA recognize oxypurinol, but use different
      interactions reflected in a nearly 26-fold difference in their affinities for
      this drug, while YgfO interacts with this analogue very inefficiently.

PMID- 16096270
TI  - Chemerin activation by serine proteases of the coagulation, fibrinolytic, and
      inflammatory cascades.
AB  - Proteases function at every level in host defense, from regulating vascular
      hemostasis and inflammation to mobilizing the "rapid responder" leukocytes of the
      immune system by regulating the activities of various chemoattractants. Recent
      studies implicate proteolysis in the activation of a ubiquitous plasma
      chemoattractant, chemerin, a ligand for the G-protein-coupled receptor CMKLR1
      present on plasmacytoid dendritic cells and macrophages. To define the
      pathophysiologic triggers of chemerin activity, we evaluated the ability of serum
      and inflammation-associated proteases to cleave chemerin and stimulate CMKLR1
      mediated chemotaxis. We showed that serine proteases factor XIIa and plasmin of
      the coagulation and fibrinolytic cascades, elastase and cathepsin G released from
      activated neutrophil granules and mast cell tryptase are all potent activators of
      chemerin. Activation results from cleavage of the labile carboxyl terminus of the
      chemoattractant at any of several different sites. Activation of chemerin by the
      serine protease cascades that trigger rapid defenses in the body may direct
      CMKLR1-positive plasmacytoid dendritic cell and tissue macrophage recruitment to
      sterile sites of tissue damage, as well as trafficking to sites of infectious and
      allergic inflammation.

PMID- 16096271
TI  - Modification of the structure and function of fibrillin-1 by homocysteine
      suggests a potential pathogenetic mechanism in homocystinuria.
AB  - Homocystinuria, a disorder originating in defects in the methionine metabolism,
      is characterized by an elevated plasma concentration of homocysteine. Most
      patients have a defect in the cystathionine-beta-synthase, the key enzyme in the
      conversion of homocysteine to cysteine. Many abnormalities in the connective
      tissue of patients with homocystinuria resemble those seen in Marfan syndrome,
      caused by mutations in fibrillin-1. These observations led to the hypothesis that
      the structure and function of fibrillin-1 is compromised in patients with
      homocystinuria. To test this hypothesis we produced recombinant human fibrillin-1
      fragments spanning the central portion of the molecule (8-Cys/transforming growth
      factor-beta binding domain 3 to calcium binding EGF domain 22) and extensively
      analyzed the potential of homocysteine to modify structural and functional
      properties of these proteins. Circular dichroism spectroscopy revealed moderate
      changes of their secondary structures after incubation with homocysteine.
      Equilibrium dialysis demonstrated a number of high affinity calcium binding sites
      in the tandemly repeated calcium binding epidermal growth factor-like domains 11
      22. Calcium binding of homocysteine-modified fragments was completely abolished.
      Incubation of the recombinant proteins with homocysteine rendered the analyzed
      calcium binding EGF domains as well as the 8-Cys/transforming growth factor-beta
      binding domain 3 significantly more susceptible to proteolytic degradation.
      Furthermore, data were obtained demonstrating that homocysteine can covalently
      modify fibrillin-1 via disulfide bonds. These data strongly suggest that
      structural and functional modifications as well as degradation processes of
      fibrillin-1 in the connective tissues of patients with homocystinuria play a
      major role in the pathogenesis of this disorder.

PMID- 16096272
TI  - Cross-talk among gp130 cytokines in adipocytes.
AB  - The interleukin-6 (IL-6) family of cytokines is a family of structurally and
      functionally related proteins, including IL-6, IL-11, leukemia inhibitory factor
      (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), and cardiotrophin
      1 (CT-1). These proteins are also known as gp130 cytokines because they all share
      gp130 as a common transducer protein within their functional receptor complexes.
      Several of these cytokines (LIF, OSM, CNTF, and CT-1) also utilize the LIF
      receptor (LIFR) as a component of their receptor complex. We have shown that all
      of these cytokines are capable of activating both the JAK/STAT and p42/44 mitogen
      activated protein kinase signaling pathways in 3T3-L1 adipocytes. By performing a
      variety of preincubation studies and examining the ability of these cytokines to
      activate STATs, ERKs, and induce transcription of SOCS-3 mRNA, we have also
      examined the ability of gp130 cytokines to modulate the action of their family
      members. Our results indicate that a subset of gp130 cytokines, in particular CT
      1, LIF, and OSM, has the ability to impair subsequent signaling activity
      initiated by gp130 cytokines. However, IL-6 and CNTF do not exhibit this cross
      talk ability. Moreover, our results indicate that the cross-talk among gp130
      cytokines is mediated by the ability of these cytokines to induce ligand
      dependent degradation of the LIFR, in a proteasome-independent manner, which
      coincides with decreased levels of LIFR at the plasma membrane. In summary, our
      results demonstrate that an inhibitory cross-talk among specific gp130 cytokines
      in 3T3-L1 adipocytes occurs as a result of specific degradation of LIFR via a
      lysosome-mediated pathway.

PMID- 16096273
TI  - A novel SET domain methyltransferase modifies ribosomal protein Rpl23ab in yeast.
AB  - In vivo studies have shown that the ribosomal large subunit protein L23a
      (Rpl23ab) in Saccharomyces cerevisiae is methylated at lysine residues. However,
      the gene encoding the methyltransferase responsible for the modification has not
      been identified. We show here that the yeast YPL208w gene product, a member of
      the SET domain family of methyltransferases, catalyzes the reaction, and we have
      now designated it Rkm1 (ribosomal lysine (K) methyltransferase 1). Yeast strains
      with deletion mutations in candidate SET domain-containing genes were in vivo
      labeled with S-adenosyl-l-[methyl-(3)H]methionine. [(3)H]Methyl radioactivity was
      determined after lysates were fractionated by SDS gel electrophoresis. When
      compared with the parent strain or other candidate deletion strains, a loss of a
      radiolabeled 15-kDa species was observed in the rkm1 (Deltaypl208w) knock-out
      strain. Treatment of wild-type cell extracts with RNase or proteinase K
      demonstrated that the methyl-accepting substrate is a protein. Cellular lysates
      from parent and knockout strains were fractionated using high salt sucrose
      gradients. Analysis of the gradient fractions by SDS gel electrophoresis
      demonstrated that the 15-kDa methyl-accepting substrate elutes with the large
      ribosomal subunit. In vitro methylation experiments using purified ribosomes
      confirmed that the methyl-accepting substrate is a ribosomal protein. Amino acid
      analysis of the in vivo labeled 15 kDa polypeptide showed that it contains
      epsilon-[(3)H]dimethyllysine residues. Mass spectrometry of tryptic peptides of
      the 15 kDa polypeptide identified it as Rpl23ab. Analysis of the intact masses of
      the large ribosomal subunit proteins by electrospray mass spectrometry confirmed
      that the substrate is Rpl23ab and that it is specifically dimethylated at two
      distinct sites by Rkm1. These results show that SET domain methyltransferases can
      be involved in translational roles as well as in the previously described
      transcriptional roles.

PMID- 16096274
TI  - Structural and mechanistic studies on carboxymethylproline synthase (CarB), a
      unique member of the crotonase superfamily catalyzing the first step in
      carbapenem biosynthesis.
AB  - The first step in the biosynthesis of the medicinally important carbapenem family
      of beta-lactam antibiotics is catalyzed by carboxymethylproline synthase (CarB),
      a unique member of the crotonase superfamily. CarB catalyzes formation of (2S,5S)
      carboxymethylproline [(2S,5S)-t-CMP] from malonyl-CoA and l-glutamate
      semialdehyde. In addition to using a cosubstrate, CarB catalyzes C-C and C-N bond
      formation processes as well as an acyl-coenzyme A hydrolysis reaction. We
      describe the crystal structure of CarB in the presence and absence of acetyl-CoA
      at 2.24 A and 3.15 A resolution, respectively. The structures reveal that CarB
      contains a conserved oxy-anion hole probably required for decarboxylation of
      malonyl-CoA and stabilization of the resultant enolate. Comparison of the
      structures reveals that conformational changes (involving His(229)) in the cavity
      predicted to bind l-glutamate semialdehyde occur on (co)substrate binding.
      Mechanisms for the formation of the carboxymethylproline ring are discussed in
      the light of the structures and the accompanying studies using isotopically
      labeled substrates; cyclization via 1,4-addition is consistent with the observed
      labeling results (providing that hydrogen exchange at the C-6 position of
      carboxymethylproline does not occur). The side chain of Glu(131) appears to be
      positioned to be involved in hydrolysis of the carboxymethylproline-CoA ester
      intermediate. Labeling experiments ruled out the possibility that hydrolysis
      proceeds via an anhydride in which water attacks a carbonyl derived from
      Glu(131), as proposed for 3-hydroxyisobutyryl-CoA hydrolase. The structural work
      will aid in mutagenesis studies directed at altering the selectivity of CarB to
      provide intermediates for the production of clinically useful carbapenems.

PMID- 16096275
TI  - Determinants of substrate specificity in omega-aminotransferases.
AB  - Ornithine aminotransferase and 4-aminobutyrate aminotransferase are related
      pyridoxal phosphate-dependent enzymes having different substrate specificities.
      The atomic structures of these enzymes have shown (i) that active site
      differences are limited to the steric positions occupied by two tyrosine residues
      in ornithine aminotransferase and (ii) that, uniquely among related, structurally
      characterized aminotransferases, the conserved arginine that binds the alpha
      carboxylate of alpha-amino acids interacts tightly with a glutamate residue. To
      determine the contribution of these residues to the specificities of the enzymes,
      we analyzed site-directed mutants of ornithine aminotransferase by rapid reaction
      kinetics, x-ray crystallography, and 13C NMR spectroscopy. Mutation of one
      tyrosine (Tyr-85) to isoleucine, as found in aminobutyrate aminotransferase,
      decreased the rate of the reaction of the enzyme with ornithine 1000-fold and
      increased that with 4-aminobutyrate 16-fold, indicating that Tyr-85 is a major
      determinant of specificity toward ornithine. Unexpectedly, the limiting rate of
      the second half of the reaction, conversion of ketoglutarate to glutamate, was
      greatly increased, although the kinetics of the reverse reaction were unaffected.
      A mutant in which the glutamate (Glu-235) that interacts with the conserved
      arginine was replaced by alanine retained its regiospecificity for the delta
      amino group of ornithine, but the glutamate reaction was enhanced 650-fold,
      whereas only a 5-fold enhancement of the ketoglutarate reaction rate resulted. A
      model is proposed in which conversion of the enzyme to its pyridoxamine phosphate
      form disrupts the internal glutamate-arginine interaction, thus enabling
      ketoglutarate but not glutamate to be a good substrate.

PMID- 16096276
TI  - Regulation of fish gill Na(+)-K(+)-ATPase by selective sulfatide-enriched raft
      partitioning during seawater adaptation.
AB  - Na(+)-K(+)-ATPase is arguably the most important enzyme in the animal cell plasma
      membrane, but the role of the membrane in its regulation is poorly understood. We
      investigated the relationship between Na(+)-K(+)-ATPase and membrane microdomains
      or "lipid rafts" enriched in sulfatide (sulfogalactosylceramide/SGC), a
      glycosphingolipid implicated as a cofactor for this enzyme, in the basolateral
      membrane of rainbow trout gill epithelium. Our studies demonstrated that when
      trout adapt to seawater (33 ppt), Na(+)-K(+)-ATPase relocates to these
      structures. Arylsulfatase-induced desulfation of basolateral membrane SGC
      prevented this relocation and significantly reduced Na(+)-K(+)-ATPase activity in
      seawater but not freshwater trout. We contend that Na(+)-K(+)-ATPase partitions
      into SGC-enriched rafts to help facilitate the up-regulation of its activity
      during seawater adaptation. We also suggest that differential partitioning of
      Na(+)-K(+)-ATPase between these novel SGC-enriched regulatory platforms results
      in two distinct, physiological Na(+) transport modes. In addition, we extend the
      working definition of cholesterol-dependent raft integrity to structural
      dependence on the sulfate moiety of SGC in this membrane.

PMID- 16096277
TI  - The residue mass of L-pyrrolysine in three distinct methylamine
      methyltransferases.
AB  - Single in-frame amber (UAG) codons are found in the genes encoding MtmB, MtbB, or
      MttB, the methyltransferases initiating methane formation from monomethylamine,
      dimethylamine, or trimethylamine, respectively, in certain Archaea. The crystal
      structure of MtmB demonstrated that the amber codon codes for pyrrolysine, the
      22nd genetically encoded amino acid found in nature. Previous attempts to
      visualize the amber-encoded residue by mass spectrometry identified only lysine,
      leaving information on the existence and structure of pyrrolysine resting
      entirely on crystallography of a single protein. Here we report successful mass
      spectral characterization of naturally occurring pyrrolysine and the first
      demonstration of the amber-encoded residue in proteins other than MtmB. The
      sequencing of chymotryptic fragments from acetonitrile-denatured proteins by
      tandem mass spectrometry revealed the mass of the amber-encoded residue in MtmB,
      MtbB, and MttB as 237.2 +/- 0.2 Da. Fourier transform ion cyclotron resonance
      mass spectrometry produced an accurate measurement for the pyrrolysyl-residue as
      237.1456 Da, within error limits of the predicted mass based on the empirical
      formula C(12)H(19)N(3)O(2). These measurements support the structure of
      pyrrolysine in MtmB as 4-methylpyrroline-5-carboxylate in amide linkage with the
      (epsilon)N of lysine but not the alternative structure in which the 4-substituent
      of the pyrroline ring is an amine group. The presence of pyrrolysine with
      statistically identical mass in all three methyltransferases is in keeping with
      the proposed direct incorporation of pyrrolysine into protein during translation
      of the UAG codon and suggests that MtbB and MttB may exploit the unusual
      electrophilicity of pyrrolysine during catalysis.

PMID- 16096278
TI  - Cyclic nucleotides, the photosynthetic apparatus and response to a UV-B stress in
      the Cyanobacterium Synechocystis sp. PCC 6803.
AB  - Cyclic nucleotides cAMP and cGMP are ubiquitous signaling molecules that mediate
      many adaptative responses in eukaryotic cells. Cyanobacteria present the
      peculiarity among the prokaryotes of having the two types of cyclic nucleotide.
      Cellular homeostasis requires both cyclases (adenylyl/guanylyl, for their
      synthesis) and phosphodiesterases (for their degradation). Fully segregated null
      mutants have been obtained for the two genes, sll1624 and slr2100, which encode
      putative cNMP phosphodiesterases. We present physiological evidence that the
      Synechocystis PCC 6803 open reading frame slr2100 could be a cGMP
      phosphodiesterase. In addition, we show that Slr2100, but not Sll1624, is
      required for the adaptation of the cells to a UV-B stress. UV-B radiation has
      deleterious effects for photosynthetic organisms, in particular on the
      photosystem II, through damaging the protein structure of the reaction center.
      Using biophysical and biochemical approaches, it was found that Slr2100 is
      involved in the signal transduction events which permit the repair of the UV-B
      damaged photosystem II. This was confirmed by quantitative reverse transcriptase
      PCR analyses. Altogether, the data point to an important role for cGMP in signal
      transduction and photoacclimation processes during a UV-B stress.

PMID- 16096279
TI  - Calmodulin binds to the cytoplasmic domain of angiotensin-converting enzyme and
      regulates its phosphorylation and cleavage secretion.
AB  - The rate of cleavage secretion of the enzymatically active ectodomain of
      angiotensin-converting enzyme (ACE) is regulated by tyrosine phosphorylation of
      the protein and by the phorbol ester, phorbol 12-myristate 13-acetate (PMA), an
      activator of protein kinase C. Here, we report that both calmodulin inhibitor
      (CaMI) and calmodulin kinase inhibitor could also enhance cleavage secretion of
      ACE. This effect was accompanied by the dissociation of calmodulin from a
      specific region within the cytoplasmic domain of ACE to which it had been bound.
      The same domain of ACE was phosphorylated, and both CaMI and PMA caused
      dephosphorylation of ACE as well. Mass spectrometric and mutational analyses
      identified Ser730 as the only phosphorylated residue in the cytoplasmic domain of
      ACE. The Ser730 --> Ala mutant of ACE was not phosphorylated, but it still bound
      calmodulin, and its cleavage secretion was enhanced by both CaMI and PMA.
      Similarly, when Ser730 was replaced by the phosphoserine mimetic, Asp, cleavage
      secretion of the resultant mutant remained susceptible to the enhancing effect of
      CaMI and PMA. These results demonstrate that, although CaMI and PMA can enhance
      both cleavage secretion of ACE and its dephosphorylation, the two effects are not
      mutually interdependent.

PMID- 16096280
TI  - Effects of RNA interference of Trypanosoma brucei structure-specific endonuclease
      I on kinetoplast DNA replication.
AB  - Kinetoplast DNA, the mitochondrial DNA of trypanosomatid protozoa, is a network
      containing several thousand topologically interlocked DNA minicircles.
      Kinetoplast DNA synthesis involves release of minicircles from the network,
      replication of the free minicircles, and reattachment of the progeny back onto
      the network. One enzyme involved in this process is structure-specific
      endonuclease-I. This enzyme, originally purified from Crithidia fasciculata, has
      been proposed to remove minicircle replication primers (Engel, M. L., and Ray, D.
      S. (1998) Nucleic Acids Res. 26, 4773-4778). We have studied the structure
      specific endonuclease-I homolog from Trypanosoma brucei, showing it to be
      localized in the antipodal sites flanking the kinetoplast DNA disk, as previously
      shown in C. fasciculata. RNA interference of structure-specific endonuclease-I
      caused persistence of a single ribonucleotide at the 5' end of both the leading
      strand and at least the first Okazaki fragment in network minicircles,
      demonstrating that this enzyme in fact functions in primer removal. Probably
      because of the persistence of primers, RNA interference also impeded the
      reattachment of newly replicated free minicircles to the network and caused a
      delay in kinetoplast DNA segregation. These effects ultimately led to shrinkage
      and loss of the kinetoplast DNA network and cessation of growth of the cell.

PMID- 16096281
TI  - Engineering functional changes in Escherichia coli endonuclease III based on
      phylogenetic and structural analyses.
AB  - Escherichia coli endonuclease III (EcoNth) plays an important cellular role by
      removing premutagenic pyrimidine damages produced by reactive oxygen species.
      EcoNth is a bifunctional enzyme that has DNA glycosylase and
      apurinic/apyrimidinic lyase activities. Using a phylogeny of natural sequences,
      we selected to study EcoNth serine 39, aspartate 44, and arginine 184, which are
      presumed to be in the vicinity of the damaged base in the glycosylase-substrate
      complex. These three amino acids are highly conserved among Nth orthologs,
      although not among homologous glycosylases, such as MutY, that have different
      base specificities and no lyase activity. To examine the role of these amino
      acids in catalysis, we constructed three mutants of EcoNth, in which Ser39 was
      replaced with leucine (S39L), Asp44 was replaced with valine (D44V), and Arg184
      was replaced with alanine (R184A), which are the corresponding residues in
      EcoMutY. We showed that EcoNth S39L does not have significant glycosylase
      activity for oxidized pyrimidines, although it maintained AP lyase activity. In
      contrast, EcoNth D44V retained glycosylase activity against oxidized pyrimidines,
      but the apparent rate constant for the lyase activity of EcoNth D44V was
      significantly lower than that of EcoNth, indicating that Asp44 in EcoNth is
      required for beta-elimination. Finally, EcoNth R184A maintained lyase activity
      but exhibited glycosylase specificity different from that of EcoNth. The
      functional consequences of each of these three substitutions can be rationalized
      in the context of high resolution protein structures. Thus phylogeny-based
      scanning mutagenesis has allowed us to identify novel roles for amino acids in
      the substrate binding pocket of EcoNth in base recognition and/or catalysis.

PMID- 16096282
TI  - Characterization of a rabbit kidney prostaglandin F(2{alpha}) receptor exhibiting
      G(i)-restricted signaling that inhibits water absorption in the collecting duct.
AB  - PGF(2alpha) is the most abundant prostaglandin detected in urine; however, its
      renal effects are poorly characterized. The present study cloned a PGF-prostanoid
      receptor (FP) from the rabbit kidney and determined the functional consequences
      of its activation. Nuclease protection assay showed that FP mRNA expression
      predominates in rabbit ovary and kidney. In situ hybridization revealed that
      renal FP expression predominates in the cortical collecting duct (CCD). Although
      FP receptor activation failed to increase intracellular Ca(2+), it potently
      inhibited vasopressin-stimulated osmotic water permeability (L(p), 10(-7)
      cm/(atm.s)) in in vitro microperfused rabbit CCDs. Inhibition of L(p) by the FP
      selective agonist latanoprost was additive to inhibition of vasopressin action by
      the EP selective agonist sulprostone. Inhibition of L(p) by latanoprost was
      completely blocked by pertussis toxin, consistent with a G(i)-coupled mechanism.
      Heterologous transfection of the rabbit FPr into HEK293 cells also showed that
      latanoprost inhibited cAMP generation via a pertussis toxin-sensitive mechanism
      but did not increase cell Ca(2+). These studies demonstrate a functional FP
      receptor on the basolateral membrane of rabbit CCDs. In contrast to the Ca(2+)
      signal transduced by other FP receptors, this renal FP receptor signals via a PT
      sensitive mechanism that is not coupled to cell Ca(2+).

PMID- 16096284
TI  - Evidence for the involvement of tyrosine kinase ZAP 70 in nuclear retinoid
      receptor-dependent transactivation in T lymphocytes.
AB  - Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are transcription
      factors that control diverse cellular functions during development and
      homeostasis. The biochemical role of these proteins in T lymphocytes is not well
      known. Here we have studied the role of protein-tyrosine kinase ZAP 70, a key
      enzyme involved in the proximal signaling events during T cell activation, in the
      modulation of RXRE- and RARE-dependent activation in T lymphocytes. Surprisingly,
      ZAP 70-negative Jurkat T cells showed considerable loss of both RXRE- and RARE
      mediated transactivation as compared with wild type Jurkat cells. In addition,
      ZAP 70-negative cells failed to exhibit normal protein kinase C and calcineurin
      induced transcriptional activity. ZAP 70-negative cells that were reconstituted
      with active ZAP 70 regained the transactivation function, whereas cells
      expressing kinase-dead form of ZAP 70 failed to do so. Defective transcriptional
      activation was also observed in actively proliferating human peripheral blood T
      lymphocytes in which RNA interference was used to induce loss of ZAP 70
      expression. In addition, an Lck-deficient Jurkat cell line that cannot
      efficiently activate ZAP 70 was also found defective in RXRE-mediated
      transcription. Finally, RNA interference-induced loss of ZAP 70 or Lck protein in
      Jurkat cells resulted in significant decrease in the RXRE-dependent activation.
      Together, these results suggest a novel functional role for ZAP 70 in nuclear
      receptor-driven transactivation in T lymphocytes.

PMID- 16096283
TI  - Free fatty acids repress the GLUT4 gene expression in cardiac muscle via novel
      response elements.
AB  - Hyperlipidemia (HL) impairs cardiac glucose homeostasis, but the molecular
      mechanisms involved are yet unclear. We examined HL-regulated GLUT4 and
      peroxisome proliferator-activated receptor (PPAR) gamma gene expression in human
      cardiac muscle. Compared with control patients, GLUT4 protein levels were 30%
      lower in human cardiac muscle biopsies from patients with HL and/or type 2
      diabetes mellitus, whereas GLUT4 mRNA levels were unchanged. PPARgamma mRNA
      levels were 30-50% lower in patients with HL and/or diabetes mellitus type 2 than
      in controls. Reporter studies in H9C2 cardiomyotubes showed that HL in vitro,
      induced by high levels of arachidonic (AA) stearic, linoleic, and oleic acids (24
      h, 200 mum) repressed transcription from the GLUT4 promoter; AA also repressed
      transcription from the PPARgamma1 and PPARgamma2 promoters. Co-expression of
      PPARgamma2 repressed GLUT4 promoter activity, and the addition of AA further
      enhanced this effect. 5'-Deletion analysis revealed three GLUT4 promoter regions
      that accounted for AA-mediated effects: two repression-mediating sequences at 
      443/-423 bp and -222/-197 bp, the deletion of either or both of which led to a
      partial derepression of promoter activity, and a third derepression-mediating
      sequence at -612/-587 bp that was required for sustaining this derepression
      effect. Electromobility shift assay further shows that AA enhanced binding to two
      of the three regions of cardiac nuclear protein(s), the nature of which is still
      unknown. We propose that HL, exhibited as a high free fatty acid level, modulates
      GLUT4 gene expression in cardiac muscle via a complex mechanism that includes:
      (a) binding of AA mediator proteins to three newly identified response elements
      on the GLUT4 promoter gene and (b) repression of GLUT4 and the PPARgamma genes by
      AA.

PMID- 16096288
TI  - Surgery for low back pain.

PMID- 16096286
TI  - Randomised controlled trial of the Lidcombe programme of early stuttering
      intervention.
AB  - OBJECTIVES: To evaluate the efficacy of the Lidcombe programme of early
      stuttering intervention by comparison to a control group. DESIGN: A pragmatic,
      open plan, parallel group, randomised controlled trial with blinded outcome
      assessment. SETTING: Two public speech clinics in New Zealand. PARTICIPANTS:
      Stuttering preschool children who presented to the speech clinics for treatment.
      Inclusion criteria were age 3-6 years and frequency of stuttering of at least 2%
      syllables stuttered. Exclusion criteria were onset of stuttering during the six
      months before recruitment and treatment for stuttering during the previous 12
      months. 54 participants were randomised: 29 to the Lidcombe programme arm and 25
      to the control arm. 12 of the participants were girls. INTERVENTION: Lidcombe
      programme of early stuttering intervention. MAIN OUTCOME MEASURES: Frequency of
      stuttering was measured as the proportion of syllables stuttered, from audiotaped
      recordings of participants' conversational speech outside the clinic. Parents in
      both arms of the trial collected speech samples in three different speaking
      situations before randomisation and at three, six, and nine months after
      randomisation. RESULTS: Analysis showed a highly significant difference (P =
      0.003) at nine months after randomisation. The mean proportion of syllables
      stuttered at nine months after randomisation was 1.5% (SD 1.4) for the treatment
      arm and 3.9% (SD 3.5) for the control arm, giving an effect size of 2.3% of
      syllables stuttered (95% confidence interval 0.8 to 3.9). This effect size was
      more than double the minimum clinically worthwhile difference specified in the
      trial protocol. CONCLUSIONS: The results provide evidence from a randomised
      controlled trial to support early intervention for stuttering. The Lidcombe
      programme is an efficacious treatment for stuttering in children of preschool
      age.

PMID- 16096289
TI  - The failure of antibiotics to prevent heart attacks.

PMID- 16096290
TI  - Combing and combating head lice.

PMID- 16096291
TI  - Why the next census needs to ask about language.

PMID- 16096293
TI  - English emergency care varies widely, commission finds.

PMID- 16096300
TI  - European water treaty hailed as a milestone for public health.

PMID- 16096303
TI  - Length of hospital stay and subsequent emergency readmission.

PMID- 16096304
TI  - Randomised controlled trial of home based motivational interviewing by midwives
      to help pregnant smokers quit or cut down.
AB  - OBJECTIVE: To determine whether motivational interviewing--a behavioural therapy
      for addictions-provided at home by specially trained midwives helps pregnant
      smokers to quit. DESIGN: Randomised controlled non-blinded trial analysed by
      intention to treat. SETTING: Clinics attached to two maternity hospitals in
      Glasgow. PARTICIPANTS: 762/1684 pregnant women who were regular smokers at
      antenatal booking: 351 in intervention group and 411 in control group.
      INTERVENTIONS: All women received standard health promotion information. Women in
      the intervention group were offered motivational interviewing at home. All
      interviews were recorded. MAIN OUTCOME MEASURES: Self reported smoking cessation
      verified by plasma or salivary cotinine concentration. RESULTS: 17/351 (4.8%)
      women in the intervention group stopped smoking (according to self report and
      serum cotinine concentration < 13.7 ng/ml) compared with 19/411(4.6%) in the
      control group. Fifteen (4.2%) women in the intervention group cut down (self
      report and cotinine concentration less than half that at booking) compared with
      26 (6.3%) in the control group. Fewer women in the intervention group reported
      smoking more (18 (5.1%) v 44 (10.7%); relative risk 0.48, 95% confidence interval
      0.28 to 0.81). Birth weight did not differ significantly (mean 3078 g v 3048 g).
      CONCLUSION: Good quality motivational interviewing did not significantly increase
      smoking cessation among pregnant women.

PMID- 16096305
TI  - Variability in interpretation of chest radiographs among Russian clinicians and
      implications for screening programmes: observational study.
AB  - OBJECTIVE: To determine variability in interpretation of chest radiographs among
      tuberculosis specialists, radiologists, and respiratory specialists. DESIGN:
      Observational study. SETTING: Tuberculosis and respiratory disease services,
      Samara region, Russian Federation. PARTICIPANTS: 101 clinicians involved in the
      diagnosis and management of pulmonary tuberculosis and respiratory diseases. MAIN
      OUTCOME MEASURES: Interobserver and intraobserver agreement on the interpretation
      of 50 digital chest radiographs, using a scale of poor to very good agreement
      (kappa coefficient: < or = 0.20 poor, 0.21-0.40 fair, 0.41-0.60 moderate, 0.61
      0.80 good, and 0.81-1.00 very good). RESULTS: Agreement on the presence or
      absence of an abnormality was fair only (kappa = 0.380, 95% confidence interval
      0.376 to 0.384), moderate for localisation of the abnormality (0.448, 0.444 to
      0.452), and fair for a diagnosis of tuberculosis (0.387, 0.382 to 0.391). The
      highest levels of agreement were among radiologists. Level of experience (years
      of work in the specialty) influenced agreement on presence of abnormalities and
      cavities. Levels of intraobserver agreement were fair. CONCLUSIONS: Population
      screening for tuberculosis in Russia may be less than optimal owing to limited
      agreement on interpretation of chest radiographs, and may have implications for
      radiological screening programmes in other countries.

PMID- 16096306
TI  - Early practical experience and the social responsiveness of clinical education:
      systematic review.
AB  - OBJECTIVES: To find how early experience in clinical and community settings
      ("early experience") affects medical education, and identify strengths and
      limitations of the available evidence. DESIGN: A systematic review rating, by
      consensus, the strength and importance of outcomes reported in the decade 1992
      2001. DATA SOURCES: Bibliographical databases and journals were searched for
      publications on the topic, reviewed under the auspices of the recently formed
      Best Evidence Medical Education (BEME) collaboration. SELECTION OF STUDIES: All
      empirical studies (verifiable, observational data) were included, whatever their
      design, method, or language of publication. RESULTS: Early experience was most
      commonly provided in community settings, aiming to recruit primary care
      practitioners for underserved populations. It increased the popularity of primary
      care residencies, albeit among self selected students. It fostered self awareness
      and empathic attitudes towards ill people, boosted students' confidence,
      motivated them, gave them satisfaction, and helped them develop a professional
      identity. By helping develop interpersonal skills, it made entering clerkships a
      less stressful experience. Early experience helped students learn about
      professional roles and responsibilities, healthcare systems, and health needs of
      a population. It made biomedical, behavioural, and social sciences more relevant
      and easier to learn. It motivated and rewarded teachers and patients and enriched
      curriculums. In some countries, junior students provided preventive health care
      directly to underserved populations. CONCLUSION: Early experience helps medical
      students learn, helps them develop appropriate attitudes towards their studies
      and future practice, and orientates medical curriculums towards society's needs.
      Experimental evidence of its benefit is unlikely to be forthcoming and yet more
      medical schools are likely to provide it. Effort could usefully be concentrated
      on evaluating the methods and outcomes of early experience provided within non
      experimental research designs, and using that evaluation to improve the quality
      of curriculums.

PMID- 16096307
TI  - The challenges of systematic reviews of educational research.

PMID- 16096309
TI  - Young people's access to tobacco, alcohol, and other drugs.

PMID- 16096310
TI  - Weapons of mass destruction--threats and responses.

PMID- 16096311
TI  - Effect of media portrayals of removal of children's tissue on UK tumour bank.

PMID- 16096312
TI  - Timing of tracheostomy in adult patients: conclusions may be premature.

PMID- 16096313
TI  - Timing of tracheostomy in adult patients: potential ramifications are alarming.

PMID- 16096314
TI  - Childhood obstructive sleep apnoea: anaesthetic implications for
      adenotonsillectomy are important.

PMID- 16096315
TI  - Childhood obstructive sleep apnoea: hypertension was not mentioned.

PMID- 16096316
TI  - Childhood obstructive sleep apnoea: covariation is not proof of cause.

PMID- 16096317
TI  - Shaving for head lice is unnecessary and distressing.

PMID- 16096318
TI  - Teaching students in general practice can affect patients' blood pressure.

PMID- 16096319
TI  - Baby growth needs proper re-evaluation.

PMID- 16096320
TI  - Global distribution of TEM-1 and ROB-1 beta-lactamases in Haemophilus influenzae.
AB  - OBJECTIVES: To determine the global distribution of TEM-1 and ROB-1 beta
      lactamases in Haemophilus influenzae isolated from patients with community
      acquired respiratory tract infection during the first 4 years of the PROTEKT
      study (1999-2003). To investigate the activities of commonly used antibiotics
      against these isolates. METHODS: For 14 870 H. influenzae, MIC testing was
      performed using NCCLS broth microdilution methodology. For 2225 beta-lactamase
      positive (BLP) H. influenzae, TEM-1 and ROB-1 genes were detected using a Taqman
      PCR method. RESULTS: beta-Lactamase positivity was 15.0% overall but varied
      greatly by country (<5% in several countries to 67.9% in Taiwan). Prevalences of
      TEM-1 and ROB-1 BLP H. influenzae were 93.7% and 4.6%, respectively, however
      almost all ROB-1 isolates were found in Canada, the USA and Mexico. ROB-1
      isolates (n = 102) were less susceptible against cefaclor (29.4% versus 87.6%)
      and cefprozil (42.2% versus 91.9%) than TEM-1 (n = 2085) isolates. Differences in
      susceptibility rates for chloramphenicol, co-trimoxazole and tetracycline were
      also found between the two groups. CONCLUSIONS: The ROB-1 beta-lactamase was
      found almost exclusively in North America and was more active against cefaclor
      and cefprozil than the TEM-1 beta-lactamase.

PMID- 16096321
TI  - Cryopreserved oocytes of infertile couples undergoing assisted reproductive
      technology could be an important source of oocyte donation: a clinical report of
      successful pregnancies.
AB  - BACKGROUND: Surplus oocytes in assisted reproduction treatment cycles could be
      saved and donated to other couples. ICSI is usually performed for oocytes that
      have been stored frozen, considering possible exocytosis of cortical granules
      (CG). The unavoidability of ICSI merits further study. METHODS: We used a slow
      method to freeze excess oocytes from infertile couples. After thawing, oocytes
      were fertilized by either IVF or ICSI according to semen parameters. Some oocytes
      were examined for CG. RESULTS: Twenty-eight infertile couples cryopreserved a
      proportion of their oocytes and 12 thawed their oocytes. Three couples used their
      own oocytes, whereas nine donated their oocytes to nine other couples for 12
      cycles. The survival rate from thawing was 90% (73/81). The fertilization rate
      using IVF (83%) was similar to ICSI (82%). Seven pregnancies (47% per cycle) were
      achieved; one used her own oocytes and six received donated oocytes. Five women
      delivered six babies including one set of twins. Two pregnancies aborted. The
      frozen-thawed oocytes (15/15) revealed no exocytosis of CG. CONCLUSIONS: To
      freeze oocytes of infertile couples undergoing assisted reproduction treatment
      may help other couples. Our successful experience may facilitate oocyte banks to
      become a reality. Both IVF and ICSI are valuable for frozen oocytes.

PMID- 16096322
TI  - Long-term reproductive outcome subsequent to medical versus surgical treatment
      for miscarriage.
AB  - BACKGROUND: When compared with the conventional surgical evacuation for the
      treatment of miscarriage, medical evacuation has been largely accepted as an
      effective and safe management. However, there is a lack of data on the long-term
      reproductive outcome of these two treatment modalities, which is crucial in
      patient counselling. The current study evaluates and compares the long-term
      fertility and pregnancy outcome following these two treatments. METHODS: A cohort
      of 604 women enrolled in a previous randomized controlled trial comparing medical
      and surgical evacuation for miscarriage were followed up prospectively by
      telephone interview at a median of 6 (range 4-9) years using a structured
      questionnaire. RESULTS: A total of 423 women were contacted and four declined to
      participate (response rate 69.4%). Of these, 261 women (131 medical and 130
      surgical evacuations) had attempted to become pregnant since the miscarriage.
      There were no differences in their baseline characteristics including age,
      reproductive and contraceptive history. The natural conception rates were the
      same (97.7%, P = 0.99) and the cumulative pregnancy rates were similar between
      groups, being 60 and 80% at 12 and 24 months respectively. The median time-to
      pregnancy was 8 months in both groups (P = 0.97) and the subsequent live birth
      rates (85.2 versus 88.2%, P = 0.72) resulting from the immediate pregnancy
      following previous treatment were similar. CONCLUSIONS: The long-term conception
      rate and pregnancy outcome are not different following medical or surgical
      evacuation for miscarriage. Women should be reassured that their long-term
      fertility potential will not be compromised after medical treatment.

PMID- 16096323
TI  - Activation of protease-activated receptor 2 stimulates proliferation and
      interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells.
AB  - BACKGROUND: Inflammation has been proposed to play essential roles in the
      pathophysiology of endometriosis, in which neutrophils and mast cells have been
      suggested to be involved. We studied whether the protease-activated receptor 2
      (PAR2), which is activated by enzymes from neutrophils and mast cells, in
      endometriotic stromal cells (ESC) has any implication in the development of the
      disease. METHODS: Cultured ESC were stimulated with various concentrations of a
      specific PAR2 agonist peptide. Proliferating activity of the cells was determined
      using immunostaining of proliferating cell nuclear antigen (a cell proliferation
      marker), 5-bromo-2'-deoxyuridine incorporation into DNA and cell count. The
      concentrations of interleukin (IL)-6 and IL-8 were measured using specific enzyme
      linked immunosorbent assay kits. The phosphorylation of three mitogen-activated
      protein kinases (MAPK), i.e. p38 MAPK, p42/44 MAPK and stress-activated protein
      Kinase/c-jun N terminal Kinase, in ESC was examined with Western blot analysis.
      RESULTS: Activation of PAR2 stimulated the proliferation of ESC and the secretion
      of IL-6 and IL-8 from ESC in a dose-dependent manner. Activation of PAR2
      stimulated the phosphorylation of all three MAPK, and inhibitors of each MAPK
      suppressed the PAR2 activation-induced proliferation of ESC. CONCLUSIONS: The
      activation of PAR2 in ESC may be involved in the pathophysiology of endometriosis
      by inducing the growth and inflammation of endometriotic lesions.

PMID- 16096324
TI  - Cost--effectiveness analysis of salpingectomy prior to IVF, based on a randomized
      controlled trial.
AB  - BACKGROUND: In patients with ultrasound-visible hydrosalpinges, salpingectomy
      prior to IVF increases the chance of a live birth. This study compared the cost
      effectiveness of this strategy (intervention) with that of optional salpingectomy
      after a failed cycle (control). METHODS: Data from a Scandinavian randomized
      controlled trial were used to calculate the individual number of treatments and
      their outcomes. Only patients with ultrasound-visible hydrosalpinges were
      considered in the main analysis, and a maximum of three fresh cycles were
      included. The costs for surgical procedures, IVF treatment, medication,
      complications, management of pregnancy and delivery as well as of early pregnancy
      losses were calculated from standardized hospital charges. RESULTS: Among the 51
      patients in the intervention group, the live birth rate was 60.8% compared with
      40.9% in 44 controls. The average cost per patient was 13,943 euro and 12,091
      euro, respectively. Thus, the average cost per live birth was 22,823 euro in the
      intervention group and 29,517 euro in the control group. The incremental cost
      effectiveness ratio for adopting the intervention strategy was estimated at 9306
      euro. CONCLUSIONS: The incremental cost to achieve the higher birth rate of the
      intervention strategy seems reasonable.

PMID- 16096325
TI  - Cyclic FEE peptide increases human gamete fusion and potentiates its RGD-induced
      inhibition.
AB  - BACKGROUND: Alpha6beta1 integrin has been proposed to act as a sperm receptor on
      the mouse oocyte by interacting with spermatozoon fertilin beta. We investigated,
      in humans, whether oocyte integrins could act similarly in gamete fusion, using a
      cyclic peptide containing the putative disintegrin-binding domain of human
      fertilin beta [cyclic FEE (cFEE)] and RGD peptide. METHODS: Zona-free eggs were
      inseminated in the absence or presence of peptides. To maintain the membrane
      protein pattern, the zona pellucida was removed by microdissection.
      Immunofluorescence and confocal microscopy were used to detect integrin subunits
      on the oocyte. RESULTS: Unexpectedly, cFEE alone increased human gamete fusion by
      94% instead of inhibiting fertilization. Furthermore, cFEE together with RGD
      potentiated the RGD-induced inhibition of fertilization in a dose-dependent
      manner. The data suggested the hypothesis of integrin cross-talk, further
      supported by the co-localization of alpha6beta1 and alphavbeta3 integrins, the
      putative receptors of cFEE and RGD peptides, respectively. CONCLUSIONS: RGD
      sensitive and -insensitive integrins may be associated in a multimolecular
      complex working as a sperm receptor on the human oocyte membrane. Supplementation
      of human IVF culture medium with cFEE peptide might improve fertilization rates
      in ART.

PMID- 16096326
TI  - Leukocyte origin and profile in follicular aspirates at oocyte retrieval.
AB  - BACKGROUND: Follicular aspirates represent a snapshot in time of conditions
      within the follicle at oocyte retrieval in women undergoing in vitro
      fertilization and embryo transfer. This clinical material has been much
      investigated and yet its cellular composition remains unclear. In this study we
      investigated the origin and profile of leukocytes found within follicular
      aspirates. METHODS: We performed morphological and immunohistochemical analyses
      of follicular aspirates and peripheral blood obtained concurrently at oocyte
      retrieval. RESULTS: There was no correlation between erythrocyte and leukocyte
      numbers in follicular aspirates. The profile of leukocyte subtypes within
      follicular aspirates was variable and differed significantly from the peripheral
      circulation in a significant proportion of the analysed samples. A subset of
      follicular aspirates displayed a marked increase in monocytes/macrophages and an
      apparent concomitant reduction in polymorphonuclear leukocytes compared with
      peripheral blood. CONCLUSIONS: Leukocytes within follicular aspirates cannot be
      accounted for solely as a result of blood vessel damage during oocyte retrieval.
      The variation in leukocyte subtypes observed in some follicular aspirates may
      reflect a coordinated infiltration of these cells, characteristic of progressive
      inflammatory responses in other systems. The possibility that leukocyte variation
      is indicative of follicular maturation deserves further investigation due to its
      potential relevance in optimizing oocyte selection.

PMID- 16096327
TI  - Beneficial response to anakinra and thalidomide in Schnitzler's syndrome.
AB  - BACKGROUND: Schnitzler's syndrome is an inflammatory disorder characterised by
      chronic urticarial rash and monoclonal gammopathy, accompanied by periodic fever,
      arthralgia or arthritis, and bone pain. The cause and treatment are still
      unknown. OBJECTIVE: To assess treatment with thalidomide and an interleukin 1
      receptor antagonist, anakinra, in Schnitzler's syndrome. CASE REPORTS: Three
      patients with Schnitzler's syndrome are described, one with IgM gammopathy, two
      with IgG type. In one patient, thalidomide induced complete remission, but was
      stopped because of polyneuropathy. Anakinra 100 mg daily in all three patients
      led to disappearance of fever and skin lesions within 24 hours. After a follow up
      of 6-18 months, all patients are free of symptoms. CONCLUSION: Anakinra proved to
      be effective in three patients with Schnitzler's syndrome. This treatment is
      preferable to thalidomide, which induced a complete remission in one of our
      patients, as it has fewer side effects.

PMID- 16096328
TI  - Antibodies against cyclic citrullinated peptide (CCP) in psoriatic patients with
      or without joint inflammation.
AB  - OBJECTIVE: To compare the prevalence of anti-CCP antibodies in psoriatic patients
      with and without joint inflammation, patients with early RA, and controls.
      METHODS: Anti-CCP antibodies (cut off level 5 U/ml) were measured in 160 patients
      with psoriatic arthritis (PsA), 146 patients with psoriasis but no arthritic
      disease, 101 patients with early RA, and 102 healthy controls by ELISA. RESULTS:
      11 (7%) patients with PsA, 75 (74%) patients with early RA, 2 (2%) healthy
      controls (2%), and 1 (0.7%) patient with psoriasis without arthritis had anti-CCP
      antibodies above the cut off level. The presence of anti-CCP antibodies was not
      related to radiological changes and/or deformity and functional impairment in
      PsA. 8/11 patients with PsA and anti-CCP antibodies had a polyarthritic disease,
      and all fulfilled the ACR criteria for RA at 4 year follow up. Five of these 8
      patients also had manifestations such as dactylitis, DIP involvement,
      radiological changes associated with PsA, and/or enthesitis. In multiple logistic
      regression analysis with polyarthritis as the dependent variable, anti-CCP
      antibodies and rheumatoid factor significantly distinguished RA from PsA.
      CONCLUSIONS: Anti-CCP antibodies were more prevalent in patients with PsA than in
      patients with psoriasis without arthritis, but less prevalent than in patients
      with early RA. Patients with PsA positive for anti-CCP antibodies more often had
      polyarthritic disease, but the presence of anti-CCP antibodies did not relate to
      radiological changes and/or deformity and functional impairment.

PMID- 16096329
TI  - First update of the international ASAS consensus statement for the use of anti
      TNF agents in patients with ankylosing spondylitis.
AB  - OBJECTIVE: To update the international recommendations for use of anti-tumour
      necrosis factor (TNF) agents in the treatment of ankylosing spondylitis. METHODS:
      The published recommendations on anti-TNF treatment in ankylosing spondylitis
      formed the basis of the update. A questionnaire was sent to the ASAS (assessment
      in ankylosing spondylitis) members before the final decisions were agreed upon at
      an international meeting of the ASAS working group. RESULTS: Only minor changes
      to the original consensus statement were required. For the initiation of anti-TNF
      treatment, there should be: a diagnosis of definitive ankylosing spondylitis
      (normally based on modified New York criteria); active disease for at least four
      weeks, as defined by a sustained Bath ankylosing spondylitis disease activity
      index (BASDAI) of > or =4 on a 0-10 scale and expert opinion based on clinical
      findings; refractory disease, defined by failure of at least two non-steroidal
      anti-inflammatory drugs during a three month period, failure of intra-articular
      steroids (if indicated), and failure of sulfasalazine in patients with
      predominantly peripheral arthritis; and application of the usual precautions and
      contraindications for biological treatment. For monitoring anti-TNF treatment:
      both the ASAS core set for clinical practice and the BASDAI should be followed
      after the initiation of treatment. Discontinuation of anti-TNF treatment in non
      responders should be considered after 6-12 weeks. Response is defined by
      improvement of at least 50% or 2 units (on a 0-10 scale) of the BASDAI.
      CONCLUSIONS: This updated consensus statement is recommended in guiding clinical
      practice and as a basis for developing national guidelines. Evaluation and
      regular update of this consensus statement is subject to further research by the
      ASAS group.

PMID- 16096331
TI  - Tumour necrosis factor alpha is expressed in refractory skin lesions from
      patients with subacute cutaneous lupus erythematosus.
AB  - OBJECTIVES: To investigate whether tumour necrosis factor alpha (TNFalpha) is
      expressed in subacute cutaneous lupus erythematosus (SCLE) skin lesions. METHODS:
      The in situ expression of TNFalpha in refractory lesional and non-lesional skin
      biopsy specimens from patients with SCLE was analysed using an
      immunohistochemical approach. At the time of biopsy these patients were receiving
      treatment with systemic medications such as antimalarial agents,
      immunosuppressive drugs, and thalidomide. Expression of TNFalpha was also
      evaluated in cutaneous lesions of patients with other inflammatory and neoplastic
      skin diseases as controls. RESULTS: The data showed that refractory lesional skin
      tissue from patients with SCLE displays a strongly positive distribution of
      TNFalpha, particularly within the epidermis. No prominent staining was seen in
      non-lesional skin from the same group of patients or in cutaneous lesions from
      the control group. CONCLUSIONS: These findings suggest that TNFalpha is localised
      and produced by epidermal cells within SCLE skin lesions and support its
      potential role in the pathogenesis of SCLE. The tissue localisation of TNFalpha
      may represent a potential therapeutic target providing a new perspective in the
      treatment of refractory skin lesions in patients with SCLE.

PMID- 16096330
TI  - Infliximab improves health related quality of life and physical function in
      patients with psoriatic arthritis.
AB  - OBJECTIVES: To evaluate the effect of infliximab on health related quality of
      life (HRQoL) and physical function in patients with active psoriatic arthritis
      (PsA) in the IMPACT 2 trial. METHODS: 200 patients with PsA unresponsive to
      conventional treatment were randomised to intravenous infusions of infliximab 5
      mg/kg or placebo at weeks 0, 2, 6, 14, and 22; patients with inadequate response
      entered early escape at week 16. HRQoL was assessed using the Short Form-36 (SF
      36) at weeks 0, 14, and 24. Functional disability was assessed using the Health
      Assessment Questionnaire (HAQ) at every visit through week 24. Associations
      between changes in quality of life (SF-36) and articular (American College of
      Rheumatology (ACR)) and dermatological (Psoriasis Area and Severity Index (PASI))
      responses were examined. RESULTS: Mean percentage improvement from baseline in
      HAQ was 48.6% in the infliximab group compared with worsening of 18.4% in the
      placebo group at week 14 (p < 0.001). Furthermore, 58.6% and 19.4% of infliximab
      and placebo treated patients, respectively, achieved a clinically meaningful
      improvement in HAQ (that is, > or = 0.3 unit decrease) at week 14 (p < 0.001).
      Increases in physical and mental component summary (PCS and MCS) scores and all
      eight scales of the SF-36 in the infliximab group were greater than those in the
      placebo group at week 14 (p < or = 0.001). These benefits were sustained through
      week 24. Patients achieving ACR20 and PASI75 responses had the greatest
      improvements in PCS and MCS scores. CONCLUSIONS: In patients with PsA, infliximab
      5 mg/kg significantly improved HRQoL and physical function compared with placebo
      through 24 weeks.

PMID- 16096332
TI  - Expression of Jak3, STAT1, STAT4, and STAT6 in inflammatory arthritis: unique
      Jak3 and STAT4 expression in dendritic cells in seropositive rheumatoid
      arthritis.
AB  - BACKGROUND: Modulation of Jak-STAT signalling may provide an effective
      therapeutic strategy in inflammatory arthritis. OBJECTIVE: To document Jak-STAT
      expression in a cohort of patients with active rheumatoid arthritis (RA),
      spondyloarthritis (SpA), and osteoarthritis (OA) and compare these subsets with
      normal synovial tissue. METHODS: Synovial tissue biopsy specimens from patients
      with RA, OA, and SpA and histologically normal tissue (n = 10 in each arthritis
      group) were examined for the presence of Jak3, STAT1, STAT4, and STAT6 expression
      using immunohistochemistry. Phenotyping was performed using immunohistochemistry
      and immunofluorescence. Clinical and serological characteristics of patients with
      RA expressing Jak3-STAT4 were assessed. RESULTS: STAT1, STAT4, and Jak3 protein
      expression was generally increased in inflammatory arthritis. In contrast, STAT6
      expression was relatively heterogeneous. A subpopulation of CD1a positive
      dendritic cells unique to seropositive patients with RA was detected. These cells
      showed intense protein expression for Jak3, STAT4, and STAT6. CONCLUSION: CD1a
      positive dendritic cells intensely express Jak3, STAT4, and STAT6 in seropositive
      RA tissue and may be an alternative marker for dendritic cells in their early
      stages of activation as well as providing a tool for identifying RA at the level
      of the synovium. Jak3 inhibition may be a potential therapeutic target to prevent
      dendritic cell maturation in RA. STAT1 expression is increased in inflammatory
      arthritis, suggesting that its pro-apoptotic and anti-inflammatory effects cannot
      effectively counteract inflammation. STAT6 expression is heterogeneous in
      synovium, suggesting a possible homoeostatic role in addition to any anti
      inflammatory effects.

PMID- 16096333
TI  - The shared epitope is a marker of severity associated with selection for, but not
      with response to, infliximab in a large rheumatoid arthritis population.
AB  - OBJECTIVE: To determine whether joint destruction, indication for, and response
      to infliximab in rheumatoid arthritis are associated with the shared epitope (SE)
      or selected cytokine gene polymorphisms (interleukin (IL) 1B, IL1-RN, and tumour
      necrosis alpha). METHODS: In a large rheumatoid arthritis population of 930
      patients from the same area (Rhone-Alpes, France), patients with (n = 198) or
      without infliximab treatment (n = 732) were compared according to their genetic
      status. Clinical, biological, and radiological data were collected. Typing for SE
      status and cytokine polymorphisms was carried out using enzyme linked
      oligosorbent assay. Statistical analysis was by chi(2) testing and calculation of
      odds ratios (OR). RESULTS: A dose relation was observed between the number of SE
      copies and joint damage in the whole rheumatoid population (OR, 1 v 0 SE copy =
      2.38 (95% confidence interval, 1.77 to 3.19), p<0.001; OR 2 v 0 SE copy = 3.92
      (2.65 to 5.80), p<0.001. The SE effect increased with disease duration but was
      not significant before two years. Selection for infliximab treatment (n = 198)
      was associated with increased disease activity, joint damage, and the presence of
      the SE with a dose effect. In all, 66.2% patients achieved an ACR20 improvement.
      No clinical or genetic factors were able to predict the clinical response to
      infliximab. CONCLUSIONS: This post-marketing study in a large cohort of
      rheumatoid arthritis patients indicates a linkage between rheumatoid arthritis
      severity, selection for treatment with infliximab, and the presence and dose of
      the SE.

PMID- 16096334
TI  - Antimalarial myopathy: an underdiagnosed complication? Prospective longitudinal
      study of 119 patients.
AB  - OBJECTIVES: To evaluate the prevalence and incidence of antimalarial myopathy in
      patients with rheumatic diseases treated with antimalarial drugs. METHODS: Over a
      three year period, all patients with rheumatic diseases who were taking
      antimalarial drugs were studied. Serum muscle enzymes were assessed at the time
      of inclusion and every six months thereafter. Muscle strength, electromyography
      (EMG), and muscle biopsy were assessed in patients with a persistent muscle
      enzyme disturbances. RESULTS: 119 patients were included (111 chloroquine, eight
      hydroxychloroquine). Of these, 22 (18.5%) had a persistent muscle enzyme
      disturbance: lactate dehydrogenase 19/22 (86%); creatine kinase 7/22 (32%), and
      aldolase 3/22 (14%). Findings of antimalarial myopathy were detected in 3/15
      biopsied patients (20%) by light microscopy and in all 15 by electron microscopy.
      Eleven patients had myopathy at the time of inclusion (prevalence 9.2%) and four
      patients developed muscle injury during follow up (annual incidence 1.2%). Muscle
      weakness was observed in 8 of 15 patients with biopsy proven myopathy, giving a
      prevalence of clinical antimalarial myopathy of 6.7%. All these patients also had
      a myopathic pattern on electromyography. CONCLUSIONS: The prevalence of
      antimalarial myopathy is higher than previously recognised when muscle enzyme
      determination is used as a screening method. When a persistent muscle enzyme
      disturbance is observed, clinical and electromyographic studies should be
      undertaken periodically to detect the development of clinical myopathy. In cases
      of clinical myopathy, an anatomical-pathological tissue study, including an
      ultrastructural study, is mandatory to confirm the diagnosis.

PMID- 16096335
TI  - Brain glucose and lactate uptake during exhaustive exercise.

PMID- 16096336
TI  - Maturation of glycinergic inhibition in the gerbil medial superior olive after
      hearing onset.
AB  - The neurones of the medial superior olive (MSO) are the most temporally sensitive
      neurones in the brain. They respond to the arrival time difference of sound at
      the two ears with a microsecond resolution; these interaural time differences are
      used to localize low-frequency sounds. In addition to the excitatory inputs from
      each ear, the MSO neurones also receive binaural glycinergic projections, which
      have a critical role in sound localization processing. Recently, it was shown
      that the glycinergic input to the MSO undergoes an experience-dependent
      structural reorganization after hearing onset. To explore the maturation of
      inhibition during the development of sound localization on a cellular level,
      glycinergic currents and potentials were measured in gerbil MSO principal cells
      from postnatal (P) day P12-P25 by whole-cell patch-clamp recordings. The synaptic
      glycinergic currents accelerated to rapid decay kinetics (approximately 2 ms) and
      rise times (approximately 0.4 ms) after hearing onset, reaching maturity around
      P17. Since the kinetics of miniature glycinergic currents did not change with
      age, it is likely that a higher degree of transmitter release synchrony is the
      underlying mechanism influencing the acceleration of the kinetics. During the
      same period, the synaptic glycinergic potentials accelerated four-fold, largely
      as a result of a prominent decrease in input resistance. In accordance with a
      reorganization of the glycinergic inputs, the evoked peak conductances decreased
      more than two-fold, together with a three-fold reduction in the frequency of
      miniature events after hearing onset. These age-dependent changes were absent in
      animals that had been reared in omni-directional noise, indicating that an
      experience-dependent pruning of synaptic inputs is important for the maturation
      of functional inhibition in the MSO. Taken together, these striking developmental
      adjustments of the glycinergic inhibition in the MSO most probably reflect an
      adaptation to improve the encoding of auditory cues with great temporal precision
      and fidelity during the maturation of sound localization behaviour.

PMID- 16096337
TI  - Epileptiform activity triggers long-term plasticity of GABA(B) receptor
      signalling in the developing rat hippocampus.
AB  - GABA(B) receptor (GABA(B)R)-mediated presynaptic inhibition regulates
      neurotransmitter release from synaptic terminals. In the neonatal hippocampus,
      GABA(B)R activation reduces GABA release and terminates spontaneous network
      discharges called giant depolarizing potentials (GDPs). Blocking GABA(B)Rs
      transforms GDPs into longer epileptiform discharges. Thus, GABA(B)R-mediated
      presynaptic inhibition of GABA release (GABA auto-inhibition) controls both
      spontaneous network activity and excitability in the developing hippocampus. Here
      we show that extensive release of endogenous GABA during epileptiform activity
      impairs GABA auto-inhibition, but not GABA(B)R-mediated inhibition of glutamate
      release, leading to hyperexcitability of the neonatal hippocampal network. Paired
      pulse depression of GABA release (PPD) and heterosynaptic depression of glutamate
      release were used to monitor the efficacy of presynaptic GABA(B)R-mediated
      inhibition in slices. PPD, but not heterosynaptic depression, was dramatically
      reduced after potassium (K+)-induced ictal-like discharges (ILDs), suggesting a
      selective impairment of GABA(B)R-dependent presynaptic inhibition of GABAergic
      terminals. Impairing GABA auto-inhibition induced a 44% increase in GDP width and
      the appearance of pathological network discharges. Preventing GABA-induced
      activation of GABA(B)Rs during ILDs avoided PPD loss and most modifications of
      the network activity. In contrast, a partial block of GABA(B)Rs induced network
      discharges strikingly similar to those observed after K+-driven ILDs. Finally,
      neither loss of GABA auto-inhibition nor network hyperexcitability could be
      observed following synchronous release of endogenous GABA in physiological
      conditions (during GDPs at 1 Hz). Thus, epileptiform activity was instrumental to
      impair GABA(B)R-dependent presynaptic inhibition of GABAergic terminals. In
      conclusion, our results indicate that endogenous GABA released during
      epileptiform activity can reduce GABA auto-inhibition and trigger pathological
      network discharges in the newborn rat hippocampus. Such functional impairment may
      play a role in acute post-seizure plasticity.

PMID- 16096338
TI  - Contribution of N- and C-terminal Kv4.2 channel domains to KChIP interaction
      [corrected].
AB  - Association of Shal gene-related voltage-gated potassium (Kv4) channels with
      cytoplasmic Kv channel interacting proteins (KChIPs) influences inactivation
      gating and surface expression. We investigated both functional and biochemical
      consequences of mutations in cytoplasmic N and C-terminal Kv4.2 domains to
      characterize structural determinants for KChIP interaction. We performed a lysine
      scanning mutagenesis within the proximal 40 amino acid portion and a structure
      based mutagenesis in the tetramerization 1 (T1) domain of Kv4.2. In addition, the
      cytoplasmic Kv4.2 C-terminus was truncated at various positions. Wild-type and
      mutant Kv4.2 channels were coexpressed with KChIP2 isoforms in mammalian cell
      lines. The KChIP2-induced modulation of Kv4.2 currents was studied with whole
      cell patch clamp and the binding of KChIP2 isoforms to Kv4.2 channels with
      coimmunoprecipitation experiments. Our results define one major interaction site
      for KChIPs, including amino acids in the proximal N-terminus between residues 11
      and 23, where binding and functional modulation are essentially equivalent. A
      further interaction site includes residues in the T1 domain. Notably, C-terminal
      deletions also had marked effects on KChIP2-dependent gating modulation and
      KChIP2 binding, revealing a previously unknown involvement of domains within the
      cytoplasmic Kv4.2 C-terminus in KChIP interaction. Less coincidence of binding
      and functional modulation indicates a more loose 'anchoring' at T1- and C
      terminal interaction sites. Our results refine and extend previously proposed
      structural models for Kv4.2/KChIP complex formation.

PMID- 16096339
TI  - A novel osmosensitive voltage gated cation current in rat supraoptic neurones.
AB  - The magnocellular neurosecretory cells of the hypothalamus (MNCs) regulate water
      balance by releasing vasopressin and oxytocin as a function of plasma osmolality.
      Release is determined largely by the rate and pattern of action potentials
      generated in the MNC somata. Changes in firing are mediated in part by a stretch
      inactivated non-selective cation current that causes the cells to depolarize when
      increased osmolality leads to cell shrinkage. We have obtained evidence for a new
      current that may regulate MNC firing during changes in external osmolality, using
      whole-cell patch clamp of acutely isolated rat MNC somata. In internal and
      external solutions lacking K+, with high concentrations of TEA, and with Na+ as
      the only likely permeant cation, the current appears as a slow inward current
      during depolarizations and yields a large tail current upon return to the holding
      potential of -80 mV. Approximately 60% of the MNCs tested (79 out of 134 cells)
      displayed a large increase in tail current density (from 5.2+/-0.9 to 10.5+/-1.4
      pA pF-1; P<0.001) following an increase in external osmolality from 295 to 325
      mosmol kg-1. The current is activated by depolarization to potentials above -60
      mV and does not appear to depend on changes in internal Ca2+. The current is
      carried by Na+ under these conditions, but is blocked by Cs+ and Ba2+ and by
      internal K+, which suggests that the current could be a K+ current under
      physiological conditions. This current could play an important role in regulating
      the response of MNCs to osmolality.

PMID- 16096340
TI  - Release kinetics, quantal parameters and their modulation during short-term
      depression at a developing synapse in the rat CNS.
AB  - We have characterized developmental changes in the kinetics and quantal
      parameters of action potential (AP)-evoked neurotransmitter release during
      maturation of the calyx of Held synapse. Quantal size (q) and peak amplitudes of
      evoked EPSCs increased moderately, whereas the fraction of vesicles released by
      single APs decreased. During synaptic depression induced in postnatal day (P) 5-7
      synapses by 10-100 Hz stimulation, q declined rapidly to 40-12% of its initial
      value. The decrease in q was generally smaller in more mature synapses (P12-14),
      but quite severe for frequencies > or = 300 Hz. The stronger decline of q in
      immature synapses resulted from a slower recovery from desensitization,
      presumably due to delayed glutamate clearance. Recovery from this desensitization
      followed an exponential time course with a time constant of approximately 480 ms
      in P5-7 synapses, and sped up > 20-fold during maturation. Deconvolution analysis
      of EPSCs revealed a significant acceleration of the release time course during
      development, which was accompanied by a 2-fold increase of the peak release rate.
      During long 100 Hz trains, more mature synapses were able to sustain average
      rates of 8-10 quanta s(-1) per active zone for phasic release. The rates of
      asynchronous vesicle release increased transiently > 35-fold immediately after
      such stimuli and decayed rapidly with an exponential time constant of
      approximately 50 ms to low resting levels of spontaneous release. However, even
      following extended periods of 100 Hz stimulation, the amount of asynchronous
      release was relatively minor with peak rates of less than 5% of the average rate
      of synchronous release measured at steady state during the tetani. Therefore, a
      multitude of mechanisms seems to converge on the generation of fast, temporally
      precise and reliable high-frequency transmission at the mature calyx of Held
      synapse.

PMID- 16096341
TI  - Role of aspartate 298 in mouse 5-HT3A receptor gating and modulation by
      extracellular Ca2+.
AB  - The TM2-TM3 extracellular loop is critical for activation of the Cys-loop family
      of ligand-gated ion channels. The contribution of aspartate 298 (D298), an amino
      acid that links the transmembrane domain 2 (TM2) to the TM2-TM3 loop, in mouse 5
      hydroxytryptamine(3A) (5-HT(3A)) receptor function was probed with site-directed
      mutagenesis in the present study. This negatively charged residue was replaced
      with an alanine to neutralize the charge, with a glutamate to conserve the
      charge, or with an arginine to reverse the charge. Human embryonic kidney 293
      (HEK 293) cells transfected with the wild-type and mutant receptors were studied
      by combining whole-cell patch-clamp recording with fast agonist application. The
      D-->A or D-->R mutations resulted in a receptor with reduced 5-HT potency, and
      accelerated kinetics of desensitization and deactivation. In addition, the
      efficacy of partial agonists was reduced by the D-->A mutation. The D-->E
      mutation produced a receptor with properties similar to those of the wild-type
      receptor. In addition, the potential role of this residue in modulation of the
      receptor by extracellular calcium ([Ca(2)(+)](o)) was investigated. Increasing
      [Ca(2)(+)](o) inhibited 5-HT-activated currents and altered receptor kinetics in
      a similar manner in the wild-type and D298E receptors, and this alteration was
      eliminated by the D-->A and D-->R mutations. Our data suggest that the charge at
      D298 participates in transitions between functional states of the 5-HT(3A)
      receptor, and provide evidence that the charge of the side-chain at residue D298
      contributes to channel gating kinetics and is crucial for Ca(2)(+) modulation.

PMID- 16096342
TI  - Domain analysis of Kv6.3, an electrically silent channel.
AB  - The subunit Kv6.3 encodes a voltage-gated potassium channel belonging to the
      group of electrically silent Kv subunits, i.e. subunits that do not form
      functional homotetrameric channels. The lack of current, caused by retention in
      the endoplasmic reticulum (ER), was overcome by coexpression with Kv2.1. To
      investigate whether a specific section of Kv6.3 was responsible for ER retention,
      we constructed chimeric subunits between Kv6.3 and Kv2.1, and analysed their
      subcellular localization and functionality. The results demonstrate that the ER
      retention of Kv6.3 is not caused by the N-terminal A and B box (NAB) domain nor
      the intracellular N- or C-termini, but rather by the S1-S6 core protein.
      Introduction of individual transmembrane segments of Kv6.3 in Kv2.1 was
      tolerated, with the exception of S6. Indeed, introduction of the S6 domain of
      Kv6.3 in Kv2.1 was enough to cause ER retention, which was due to the C-terminal
      section of S6. The S4 segment of Kv6.3 could act as a voltage sensor in the Kv2.1
      context, albeit with a major hyperpolarizing shift in the voltage dependence of
      activation and inactivation, apparently caused by the presence of a tyrosine in
      Kv6.3 instead of a conserved arginine. This study suggests that the silent
      behaviour of Kv6.3 is largely caused by the C-terminal part of its sixth
      transmembrane domain that causes ER retention of the subunit.

PMID- 16096344
TI  - Retardation of removal of radiation-induced apoptotic cells in developing neural
      tubes in macrophage galactose-type C-type lectin-1-deficient mouse embryos.
AB  - MGL1/CD301a is a C-type lectin that recognizes galactose and N
      acetylgalactosamine as monosaccharides and is expressed on limited populations of
      macrophages and dendritic cells at least in adult mice. In this study, pregnant
      mice with Mgl1+/- genotype were mated with Mgl1+/- or Mgl1-/- genotype males, and
      the embryos were used to assess a hypothesis that this molecule plays an
      important role in the clearance of apoptotic cells. After X-ray irradiation at 1
      Gy of developing embryos at 10.5 days post coitus (d.p.c.), the number of Mgl1-/-
      pups was significantly reduced as compared with Mgl1+/+ pups. Distributions of
      MGL1-positive cells, MGL2-positive cells, and apoptotic cells were histologically
      examined in irradiated Mgl1+/+ embryos. MGL1-positive cells were detected in the
      neural tube in which many cells undergo apoptosis, whereas MGL2-positive cells
      were not observed. Biotinylated recombinant MGL1 bound a significant portion of
      the apoptotic cells. When Mgl1+/+ and Mgl1-/- embryos were examined for the
      presence of apoptotic cells, similar numbers of apoptotic cells gave rise, but
      the clearance of these cells was slower in Mgl1-/- embryos than in Mgl1+/+
      embryos. These results strongly suggest that MGL1/CD301a is involved in the
      clearance of apoptotic cells. This process should be essential in the repair and
      normal development of X-ray-irradiated embryos.

PMID- 16096343
TI  - Relative contribution of Ia inhibitory interneurones to inhibition of feline
      contralateral motoneurones evoked via commissural interneurones.
AB  - The aim of the study was to examine to what extent the crossed inhibition of
      hindlimb lumbar alpha-motoneurones is evoked via interneurones that mediate
      reciprocal inhibition between flexors and extensors (Ia inhibitory
      interneurones), and to what extent via other spinal interneurones. The crossed
      inhibition was evoked by reticulospinal and vestibulospinal tract fibres,
      stimulated in the contralateral medullary longitudinal fascicle and the lateral
      vestibular nucleus, respectively, or by group II muscle afferents in the
      contralateral quadriceps nerve. The components of the IPSPs recorded in
      motoneurones that were mediated by Ia inhibitory interneurones were identified by
      their depression following activation of Renshaw cells. Trisynaptic components of
      IPSPs of reticulospinal and vestibulospinal origin, and polysynaptic (but not
      trisynaptic) components of IPSPs from group II afferents were found to be
      depressed in the majority of the motoneurones, while disynaptic components, those
      due to direct actions of inhibitory commissural interneurones, were not
      depressed. These results indicate that the coordination of left and right
      hindlimb movements based on crossed inhibition from reticulospinal and
      vestibulospinal neurones, depends on the degree of activation of Ia inhibitory
      interneurones by muscle spindle afferents and on their inhibition by Renshaw
      cells. Our results also indicate that Ia inhibitory interneurones do not operate
      as last-order inhibitory interneurones in crossed trisynaptic pathways from group
      II afferents, even though they mediate inhibition evoked by interneurones in
      shared polysynaptic pathways of crossed flexor and extensor reflexes coactivated
      by group II and other high-threshold muscle, skin and joint afferents.

PMID- 16096345
TI  - Two oligosaccharyl transferase complexes exist in yeast and associate with two
      different translocons.
AB  - Oligosaccharyl transferase (OT) scans and selectively glycosylates -Asn-X-Thr/Ser
      motifs in nascent polypeptide chains in the endoplasmic reticulum (ER). Several
      groups have reported different results for the composition of this enzyme
      complex. In this study, using a membrane protein two-hybrid approach, the split
      ubiquitin system, we show that except for Ost3p and Ost6p, all of the other
      subunits of OT exist as dimers or oligomers in the yeast, Saccharomyces
      cerevisiae. Ost3p and Ost6p behave strikingly similar in a series of genetic and
      biochemical assays, but clearly do not exist in the same OT complex. This
      observation, as well as the results in an accompanying study to analyze the
      composition of OT complex by blue native gel electrophoresis using a series of
      wild-type and mutant yeast strains strongly suggests that two isoforms of the OT
      complex exist in the ER, differing only in the presence of Ost3p or Ost6p. Each
      of these two isoforms of the OT complex specifically interacts with two
      structurally similar, but functionally different translocon complexes: the Sec61
      and the Ssh1 translocon complexes.

PMID- 16096346
TI  - The 3.4-kDa Ost4 protein is required for the assembly of two distinct
      oligosaccharyltransferase complexes in yeast.
AB  - In the central reaction of N-linked glycosylation, the oligosaccharyltransferase
      (OTase) complex catalyzes the transfer of a lipid-linked core oligosaccharide
      onto asparagine residues of nascent polypeptide chains in the lumen of the
      endoplasmic reticulum (ER). The Saccharomyces cerevisiae OTase has been shown to
      consist of at least eight subunits. We analyzed this enzyme complex, applying the
      technique of blue native gel electrophoresis. Using available antibodies, six
      different subunits were detected in the wild-type (wt) complex, including Stt3p,
      Ost1p, Wbp1p, Swp1p, Ost3p, and Ost6p. We demonstrate that the small 3.4-kDa
      subunit Ost4p is required for the incorporation of either Ost3p or Ost6p into the
      complex, resulting in two, functionally distinct OTase complexes in vivo. Ost3p
      and Ost6p are not absolutely required for OTase activity, but modulate the
      affinity of the enzyme toward different protein substrates.

PMID- 16096347
TI  - SPLINDID: a semi-parametric, model-based method for obtaining transcription rates
      and gene regulation parameters from genomic and proteomic expression profiles.
AB  - PURPOSE: To evaluate a semi-parametric, model-based approach for obtaining
      transcription rates from mRNA and protein expression. METHODS: The transcription
      profile input was modeled using an exponential function of a cubic spline and the
      dynamics of translation; mRNA and protein degradation were modeled using the
      Hargrove-Schmidt model. The transcription rate profile and the translation, and
      mRNA and protein degradation rate constants were estimated by the maximum
      likelihood method. RESULTS: Simulated datasets generated from the stochastic,
      transit compartment and dispersion signaling models were used to test the
      approach. The approach satisfactorily fit the mRNA and protein data, and
      accurately recapitulated the parameter and the normalized transcription rate
      profile values. The approach was successfully used to model published data on
      tyrosine aminotransferase pharmacodynamics. CONCLUSIONS: The semi-parametric
      approach is effective and could be useful for delineating the genomic effects of
      drugs. AVAILABILITY: Code suitable for use with the ADAPT software program is
      available from the corresponding author. CONTACT: murali@acsu.buffalo.edu.

PMID- 16096348
TI  - ROCR: visualizing classifier performance in R.
AB  - ROCR is a package for evaluating and visualizing the performance of scoring
      classifiers in the statistical language R. It features over 25 performance
      measures that can be freely combined to create two-dimensional performance
      curves. Standard methods for investigating trade-offs between specific
      performance measures are available within a uniform framework, including receiver
      operating characteristic (ROC) graphs, precision/recall plots, lift charts and
      cost curves. ROCR integrates tightly with R's powerful graphics capabilities,
      thus allowing for highly adjustable plots. Being equipped with only three
      commands and reasonable default values for optional parameters, ROCR combines
      flexibility with ease of usage. AVAILABILITY: http://rocr.bioinf.mpi-sb.mpg.de.
      ROCR can be used under the terms of the GNU General Public License. Running
      within R, it is platform-independent. CONTACT: tobias.sing@mpi-sb.mpg.de.

PMID- 16096349
TI  - A geometric invariant-based framework for the analysis of protein conformational
      space.
AB  - MOTIVATION: Characterization of the restricted nature of the protein local
      conformational space has remained a challenge, thereby necessitating a
      computationally expensive conformational search in protein modeling. Moreover,
      owing to the lack of unilateral structural descriptors, conventional data mining
      techniques, such as clustering and classification, have not been applied in
      protein structure analysis. RESULTS: We first map the local conformations in a
      fixed dimensional space by using a carefully selected suite of geometric
      invariants (GIs) and then reduce the number of dimensions via principal component
      analysis (PCA). Distribution of the conformations in the space spanned by the
      first four PCs is visualized as a set of conditional bivariate probability
      distribution plots, where the peaks correspond to the preferred conformations.
      The locations of the different canonical structures in the PC-space have been
      interpreted in the context of the weights of the GIs to the first four PCs.
      Clustering of the available conformations reveals that the number of preferred
      local conformations is several orders of magnitude smaller than that suggested
      previously. SUPPLEMENTARY INFORMATION: www.it.iitb.ac.in/~ashish/bioinfo2005/.

PMID- 16096350
TI  - Voltage-dependent calcium channels.
AB  - Voltage-activated calcium channels can be divided into two subgroups based on
      their activation threshold, low-voltage-activated (LVA) and high-voltage
      activated (HVA). Auxiliary subunits of the HVA calcium channels contribute
      significantly to biophysical properties of the channels. We have cloned and
      characterized members of two families of auxiliary subunits: alpha2delta and
      gamma. Two new alpha2delta subunits, alpha2delta-2 and alpha2delta-3, regulate
      all classes of HVA calcium channels. While the ubiquitous alpha2delta-2 modulates
      both neuronal and non-neuronal channels with similar efficiency, the alpha2delta
      3 subunit regulates Ca(v)2.3 channels more effectively. Furthermore, alpha2delta
      2 may modulate the LVA Ca(v)3.1 channel. Four new gamma subunits, gamma-2, gamma
      3, gamma-4 and gamma-5, were characterized. The gamma-2 subunit modulated both
      the non-neuronal Ca(v)1.2 channel and the neuronal Ca(v)2.1 channel. The gamma-4
      subunit affected only the Ca(v)2.1 channel. The gamma-5 subunit may be a
      regulatory subunit of the LVA Ca(v)3.1 channel. The Ca(v)1.2 channel is a major
      target for treatment of cardiovascular diseases. We have mapped the interaction
      site for clinically important channel blockers - dihydropyridines (DHPs) - and
      analysed the underlying inhibition mechanism. High-affinity inhibition is
      characterized by interaction with inactivated state of the channel. Its
      structural determinants are amino acids of the IVS6 segment, with smaller
      contribution of the IS6 segment, which contributes to voltage-dependence of DHP
      inhibition. Removal of amino acids responsible for the high-affinity inhibition
      revealed a low-affinity open channel block, in which amino acids of the IIIS5 and
      IIIS6 segments take part. Experiments with a permanently charged DHP suggested
      that there is another low-affinity interaction site on the alpha(1) subunit. We
      have cloned and characterized murine neuronal LVA Ca(v)3.1 channel. The channel
      has high sensitivity to the organic blocker mibefradil, moderate sensitivity to
      phenytoin, and low sensitivity to ethosuximide, amiloride and valproat. The
      channel is insensitive to tetrodotoxin and DHPs. The inorganic blockers Ni2+ and
      Cd2+ are moderately effective compared to La3+. The current through the Ca(v)3.1
      channel inactivates faster with Ba2+ compared to Ca2+. Molecular determinants of
      fast inactivation are located in amino side of the intracellular carboxy
      terminus. The voltage dependence of charge movement is very shallow compared to
      the voltage dependence of current activation. Transfer of 30 % of charge
      correlates with activation of 70 % of measurable macroscopic current. Prolonged
      depolarization does not immobilize charge movement of the Ca(v)3.1 channel.

PMID- 16096351
TI  - The prophylactic and therapeutic effects of cholinolytics on perfluoroisobutylene
      inhalation induced acute lung injury.
AB  - Perfluoroisobutylene (PFIB) is a kind of fluoro-olefin that is ten times more
      toxic than phosgene. The mechanisms of the acute lung injury (ALI) induced by
      PFIB inhalation remain unclear. To find possible pharmacological interventions,
      mice and rats were exposed to PFIB, and the prophylactic or therapeutic effects
      of 3-quinuclidinyl benzilate (QNB) and anisodamine were studied and confirmed. It
      was observed that the wet lung/body weight and the dry lung/body weight ratios at
      24 h after PFIB exposure (130 mg/m(3) for 5 min) were significantly decreased
      when a single dose of QNB (5 mg/kg) was administered intraperitoneally either 30
      min before exposure or 10 h after exposure. Anisodamine was without any
      prophylactic or therapeutic effects at single doses below 30 mg/kg. The effects
      of QNB against PFIB inhalation induced ALI were well evidenced by the
      significantly decreased mice mortality at 72 h, the total protein concentration
      in bronchoalveolar lavage fluid at 24 h after the PFIB exposure, as well as the
      ultrastructural observations. The analysis of the time courses of lung sulfhydryl
      concentration, myeloperoxidase (MPO) activity and hemorheology assay showed that
      the toxicity of PFIB may be due to consumption of lung protein sulfhydryl, influx
      of polymorphonuclear leukocytes (PMNs) into the lung, and increased peripheral
      blood viscosity at a low shear rate, all of which were partially blocked by QNB
      intervention except for PMN influx. The results suggest that cholinolytics might
      have prophylactic and therapeutic roles in PFIB inhalation induced ALI.

PMID- 16096352
TI  - Oxidant-antioxidant status and pulmonary function in welding workers.
AB  - Welding is a process during which fumes, gases, electromagnetic radiation and
      noise are emitted as by-products. Metal oxide particles are particularly
      hazardous components of welding fumes. Welding has been found to be associated
      with respiratory symptoms and our objective in the present study was to study the
      effects of welding on pulmonary function and serum oxidant-antioxidant status.
      Fifty-one welding workers and 31 control subjects were recruited. Face to face
      interviews were conducted using the respiratory illness questionnaire adapted
      from the American Thoracic Society with the addition of demographic
      characteristics, work history and working conditions. Additionally physical
      examinations and spirometric measurements were performed at workplaces.
      Thiobarbituric acid reactive substances (TBARS), protein carbonyls, protein
      sulfhydryls (SH) and erythrocyte reduced glutathione (GSH) levels were measured
      to evaluate oxidant-antioxidant status in 34 welding workers and in 20 control
      subjects. No statistically significant differences were observed in age, height,
      weight, body mass index (BMI), smoking status and annual working durations
      between welding workers and controls. Coughing, sputting and wheezing were
      significantly higher in welding workers (p<0.05). When adjusted for age, BMI and
      smoking status in logistic regression, welding work showed a significant risk for
      chronic bronchitis (OR: 4.78, 95%CI: 1.30-17.54). Forced expiratory volume in one
      second (FEV(1))/forced vital capacity (FVC) and four parameters of forced
      expiratory flow (FEF: FEF(25), FEF(50), FEF(75), FEF(25-75)) levels measured in
      the welding workers were significantly lower than those in the control group
      (p<0.05). Serum TBARS and protein carbonyl levels were higher in welding workers
      than those in controls (p<0.001, p<0.05, respectively). On the other hand, total
      protein SH groups and GSH levels were significantly lower in welders than those
      in controls (p<0.05, p<0.001, respectively). Pulmonary function tests and oxidant
      antioxidant status were found to be negatively affected in welding workers
      chronically exposed to welding fumes and gases. Preventive measures should be
      taken to improve the health status of these workers.

PMID- 16096353
TI  - Oral toxicity of bismuth in rat: single and 28-day repeated administration
      studies.
AB  - The consumption and production of bismuth are increasing, however there is very
      little information about the direct toxic effect of bismuth. The present study
      aimed to characterize the potential toxic effects of bismuth through oral
      administration and observation for fourteen days following single dose of 0 and
      2,000 mg/kg (acute oral toxicity study), and repeated oral administration for
      twenty-eight days at dose levels of 0, 40, 200, and 1,000 mg/kg daily (28-d
      repeated oral dose toxicity study) to male and female Crj:CD (SD) IGS rats (SPF).
      We found no deaths and no abnormalities in clinical signs, body weights, and
      necropsy findings for any of the animals in the acute oral toxicity study and no
      changes attributable to bismuth in either males or females in the dose group up
      to 1,000 mg/kg of the 28-d repeated-dose toxicity study. Therefore, we determined
      that the lethal dose with a 50% mortality rate (LD50) is greater than 2,000 mg/kg
      and the no-observed-adverse-effect level (NOAEL) of bismuth is 1,000 mg/kg in
      both sexes. We conclude that the adverse toxic effects of bismuth as a simple
      metal substance are low compared to lead toxicity under the conditions tested in
      our studies.

PMID- 16096354
TI  - Effects of sarin on the nervous system of subway workers seven years after the
      Tokyo subway sarin attack.
AB  - This study was designed to assess the after effects of sarin exposure on the
      nervous system in victims of the Tokyo Subway Sarin Attack, which occurred on 20
      March, 1995. We performed a similar study 3 yr after the disaster. This time, we
      newly enrolled 36 staff of the Teito Rapid Transit Authority (Tokyo Eidan subway)
      to assess the 7 yr after effects on the nervous system, and merged previous data
      including unpublished data to enhance statistical power. New subjects consisted
      of 23 male exposed subjects and 13 referent subjects matched for age and working
      types. Neurobehavioral tests for psychomotor function and memory, stabilometry,
      and Benton visual retention test were performed. As reported previously, the
      exposed group performed significantly less well in the psychomotor function test
      (tapping) than the referent group (117.8 +/- 1.2 vs. 105.6 +/- 1.2 msec). Using
      merged data, this phenomenon was also observed in a dose-dependent manner and the
      exposed group performed significantly less well in the backward digit span test
      (4.47 +/- 1.17 vs. 5.11 +/- 1.65 digits). These results indicate that chronic
      decline of psychomotor function and memory function still exist 7 yr after the
      sarin exposure.

PMID- 16096355
TI  - Knowledge, attitude and practice regarding organic solvents among printing
      workers in Hong Kong.
AB  - To find out the prevalence of good knowledge, appropriate attitude and safe
      practice among printing workers exposed to organic solvents in Hong Kong, and to
      see if safe practice was influenced by the knowledge of and the attitude towards
      the harmful effects of organic solvents as well as other factors. The survey was
      conducted in a sample of 501 male printing workers from 28 factories in Hong
      Kong. The knowledge of and attitude towards the harmful effects of organic
      solvents, as well as the good practices adopted by the workers when handling
      solvents were explored using a questionnaire. Multiple logistic regression
      analysis was conducted to identify the major factors that influenced the
      knowledge, attitude and practice of workers. The prevalence of good knowledge,
      appropriate attitude and safe practice was low, being 20.4%, 38.4% and 22.0%
      respectively. Good knowledge was positively associated with awareness of the
      relevant legislation and past drinking behavior and negatively associated with
      current smoking. Appropriate attitude depended on having good knowledge and
      younger age. Safe practice did not depend on knowledge and attitude, but was
      positively associated with being informed of safety precautions and being
      supplied with chemical information by supervisors. The majority of workers
      believed that their employers, the Government and other statutory bodies should
      be responsible for providing information on chemicals, but very few of them
      actually obtained information from these sources. More workers preferred
      publications and talks rather than television as the means of obtaining further
      knowledge on chemicals. Front line supervisors have a pivotal role to play in
      improving safe practices of workers by informing them of the necessary
      precautions and supplying the relevant chemical information.

PMID- 16096356
TI  - Prevalence and psychosocial risk factors of upper extremity musculoskeletal pain
      in industries of Taiwan: a nationwide study.
AB  - Prevalence of upper extremity disorders and their associations with psychosocial
      factors in the workplace have received more attention recently. A national survey
      of cross-sectional design was performed to determine the prevalence rates of
      upper extremity disorders among different industries. Trained interviewers
      administered questionnaires to 17,669 workers and data on musculoskeletal
      complaints were obtained along with information on risk factors. Overall the 1
      year prevalence of neck (14.8%), shoulder (16.6%), and hand (12.4%) disorders
      were higher than those of the upper back (7.1%) and elbow (8.3%) among those who
      sought medical treatment due to the complaint. Workers in construction and
      agriculture-related industries showed a higher prevalence of upper extremity
      disorders. After multiple logistic regression adjusted for age, education, and
      employment duration, we found job content, physical working condition, a
      harmonious interpersonal relationship at the workplace and organizational
      problems were significant determinants of upper extremity disorders in
      manufacturing and service industries. Male workers in manufacturing industries
      showed more concern about physical working conditions while female workers in
      public administration emphasized problems of job content and interpersonal
      relationships. We concluded that these factors were major job stressors
      contributing to musculoskeletal pain of the upper extremity.

PMID- 16096357
TI  - Exposure assessment to suggest the cause of sinusitis developed in grinding
      operations utilizing soluble metalworking fluids.
AB  - A worker who ground the inner parts of camshafts for automobile engines using
      water-soluble metalworking fluid (MWF) for 14 yr was diagnosed with sinusitis. We
      postulated that the cause of sinusitis might be associated with exposure to
      microbes contaminating the water-soluble MWF used in the grinding operation. To
      uncover responsible agents for this case of sinusitis, a quantitative exposure
      assessment for chemical and biological agents was made and prevalence of work
      related respiratory symptoms was investigated by questionnaire. The exposure
      ranges of MWF mist (0.59 mg/m(3) to 2.12 mg/m(3)) measured during grinding
      exceeded 0.5 mg/m(3) of the recommended exposure limit (REL). Grinders' exposures
      to bacteria, fungi and endotoxins were also generally higher than not only the
      proposed standards, but also those reported by several studies investigating the
      causes of respiratory effects. Statistical tests indicated that the prevalence
      rate of reported symptoms related to nasal cavities showed no significant
      differences among the operations. Evaluation of grinding operation
      characteristics and the quantitative exposure assessment indicated that repeated
      exposure to MWF mist, including water-soluble MWF contaminated with microbes may
      cause respiratory diseases like sinusitis or at least increase susceptibility to
      the development of sinusitis. Further study is underway to identify environmental
      risk factors for sinusitis by analyzing the relationship between medical
      examination results and plant characteristics including exposure data.

PMID- 16096358
TI  - Relationship between turnover and periodic health check-up data among Japanese
      hospital nurses: a three-year follow-up study.
AB  - The present study explored the relationship between turnover and periodic health
      check-up data among Japanese hospital nurses. The subjects were 379 registered
      nurses in a Japanese hospital and the duration of our study period was three
      years. By the proportional hazard model, we investigated the relative risks (RRs)
      of the turnover rate associated with the following: lifestyles (irregularity of
      meals, taking breakfast), work environment (working hours, work schedule), and
      health status (body mass index [BMI], serum total cholesterol [T-cho], taking
      medication, sleep disturbance). We obtained the data on turnover from October,
      1997 to September, 2000. During the observed period we were able to follow up on
      363 female nurses (96%) and the turnover total amongst them was 100. We divided
      the subjects into a younger (21-25-yr-old) and an older (>25-yr-old) group
      because of the interaction between age and turnover. In the younger group, we
      found that sleep disturbance influenced turnover significantly. On the other
      hand, in the older nurses, BMI and T-cho contributed to turnover significantly.
      Our results imply the possibility of a partial association between turnover and
      periodic health check-up data among the nurses.

PMID- 16096359
TI  - Relationship between turnover and burnout among Japanese hospital nurses.

PMID- 16096361
TI  - Occupational allergic contact dermatitis due to ultraviolet-cured acrylic glue.

PMID- 16096360
TI  - Determination of urinary phenolic metabolites from rats treated with 1,2,3- and
      1,3,5- trimethylbenzenes.

PMID- 16096362
TI  - A study of heat stress parameters at Kozlu Coalmine, Turkey.

PMID- 16096363
TI  - Silicosis caused by sandblasting of jeans in Turkey: a report of two concomitant
      cases.

PMID- 16096364
TI  - Environmental and biological monitoring in a lead acid battery manufacturing unit
      in India.
AB  - An environmental and biological monitoring of a lead acid battery manufacturing
      unit was carried out to measure the respirable particulate matter, lead content
      in working atmosphere and blood lead levels of workers employed in different
      sections. The results showed high mean air lead concentration in buffing (1444.45
      microg/m(3)), plate cutting (430.14 microg/m(3)) and pasting (277.48 microg/m(3))
      sections. The mean blood lead levels of employees in these sections were also
      higher than the values prescribed by ACGIH.

PMID- 16096365
TI  - The role of PRAJA and ELF in TGF-beta signaling and gastric cancer.
AB  - Emerging research has shown that the transforming growth factor-beta (TGF-beta)
      pathway plays a key role in the suppression of gastric carcinoma. Biological
      signals for TGF-beta are transduced through transmembrane serine/threonine kinase
      receptors, which in turn signal to Smad proteins. Inactivation of the TGF-beta
      pathway often occurs in malignancies of the gastrointestinal system, including
      gastric cancer. Yet, only a fraction of sporadic gastric tumors exhibit
      inactivating mutations in early stages of cancer formation, suggesting that other
      mechanisms play a critical role in the inactivation of this pathway. Smad4, a
      tumor suppressor, is often mutated in human gastrointestinal cancers. The
      mechanism of Smad4 inactivation, however, remains uncertain and could be mediated
      through E3-mediated ubiquitination of Smad4/adaptor protein complexes. The
      regulation of the TGF-beta pathway through a PRAJA, a RING finger (RING-H2)
      protein, and ELF, a beta-Spectrin adaptor protein, both which were originally
      identified in endodermal stem/progenitor cells committed to foregut lineage,
      could play a pivotal role in gastric carcinogenesis. PRAJA, which functions as an
      E3 ligase, interacts with ELF in a TGF-beta-dependent manner in gastric cancer
      cell lines. PRAJA is increased five-fold in human gastric cancers, and
      inactivates ELF. This is particularly significant since ELF, a Smad4 adaptor
      protein, possesses potent anti-oncogenic activity and is frequently seen to be
      inactivated in carcinogenic gastric cells. Strikingly, PRAJA manifests
      substantial E3-dependent ubiquitination of ELF and Smad3, but not Smad4. The
      alteration of ELF and/or Smad4 expression and function in the TGF-beta signaling
      pathway may be induced by enhancement of ELF degradation, which is mediated by
      the high level expression of PRAJA in gastrointestinal cancers. These studies
      reveal a mechanism for gastric tumorigenesis whereby defects in adaptor proteins
      for Smads, such as ELF, can undergo degradation by PRAJA, through the ubiquitin
      mediated pathway.

PMID- 16096366
TI  - Elevated sphingomyelinase activity and ceramide concentration in serum of
      patients undergoing high dose spatially fractionated radiation treatment:
      implications for endothelial apoptosis.
AB  - Spatially fractionated high dose (grid) radiation treatment (SFGRT) involves
      irradiation of bulky tumors with one high, grid-delivered, dose of 15 Gy followed
      by multiple consecutive doses of 2 Gy each. The goal of this study is to
      determine the effect of this treatment on serum ceramide content and to
      investigate possible involvement of ceramide in tumor regression after SFGRT.
      Serum ceramide and Secretory SMase (S-SMase) were quantified in 11 patients
      before and at 24, 48 and 72 h after the dose of 15 Gy. Furthermore, LDL particles
      were isolated from the serum and their apoptotic ability was tested in human
      endothelial cells by TUNEL assay. Sixty seven per cent (6/8) of the patients with
      partial (PR) or complete (CR) response showed statistically significant increase
      in serum ceramide levels. Of the nonresponders in the study, none showed an
      elevation in ceramide. S-SMase activity underwent similar changes. LDL particles
      from serum of patients collected 72 hours after SFGRT sensitized the endothelial
      cells to undergo apoptosis in response to 5 Gy radiation that by itself had only
      modest effect on cell death. Independent elevation of ceramide content of
      endothelial cells that were otherwise resistant to radiation-induced cell death
      also was sufficient to sensitize these cells to apoptosis. Serum S-SMase activity
      and ceramide content increase following SFGRT and correlate with the clinical
      response. Apparently, these changes are in the LDL-associated ceramide and may
      contribute to better tumor reduction after SFGRT, due to the ability of LDL
      derived ceramide to sensitize endothelial cells for apoptosis.

PMID- 16096367
TI  - Identification of thioredoxin reductase 1-regulated genes using small
      interference RNA and cDNA microarray.
AB  - Thioredoxin reductase 1 (TrxR1) is a cytosolic enzyme that plays a central role
      in controlling cellular redox homeostasis. TrxR1 can transduce regulatory redox
      signals through NADPH-dependent reduction of thioredoxin (Trx), which is able to
      reduce a broad spectrum of target enzymes and regulate the activity of several
      transcription factors (e.g., p53 and NF-kappaB). The TrxR1/Trx system is involved
      in every step of cancer biology, ranging from transformation and progression to
      invasion, metastasis and resistance to therapy. TrxR1 was also recently
      identified as one key enzyme involved in cell death induced by interferon-beta
      (IFN-beta)/all-trans retinoic acid (ATRA) anti-cancer treatment. Our study
      employed small interference RNA (siRNA) and microarray techniques to investigate
      the effect of TrxR1 silencing on gene expression in HepG2 cells. We also
      investigated TrxR1-mediated cell response to IFN-beta/ATRA treatment. We
      identified TrxR1-dependent genes with functions related to several cellular
      processes such as apoptosis (SOX4), ubiquitination (Ubiquitin D, F-box protein
      25), organization of cytoskeletal/extracellular matrix (Keratin 19, Fibronectin
      1) and transport (Cystine/Glutamate transporter). We also investigated the effect
      of TrxR1 siRNA on the protein profile using surface enhanced laser desorption
      ionization time-of-flight (SELDI-TOF) technology. Profiles confirmed significant
      involvement of TrxR1 in cell response to IFN-beta/ATRA.

PMID- 16096368
TI  - In vitro pharmacological characterization of TKI-28, a broad-spectrum tyrosine
      kinase inhibitor with anti-tumor and anti-angiogenic effects.
AB  - Tyrosine kinases are used as important biomarkers in many tumor types.
      Preclinical and clinical anti-tumor studies have shown that broadly acting
      tyrosine kinase inhibitors may be more useful than specific inhibitors, since the
      former might overcome redundancies and crosstalk in tumor cell growth signaling
      pathways. Here, we aim to identify a novel potent tyrosine kinase inhibitor.
      Computer modeling of the pyrido-pyrimidine class compound, TKI-28(6-(2,6
      dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidine-7-one),
      predicted that the compound would dock well in the ATP pocket of the ErbB-2
      tyrosine kinase, yielding a high binding affinity for ErbB receptors. Biochemical
      studies revealed that TKI-28 potently inhibited the activities of tyrosine
      kinases such as ErbB-2, EGFR, KDR, PDGFRbeta, c-kit and c-Src, but had little
      effect on Flt-1 in cell-free system. TKI-28 also efficiently blocked
      autophosphorylation of the listed receptor tyrosine kinases, and subsequently
      downregulated phosphorylation of many downstream signaling proteins at the
      cellular level. TKI-28 exhibited a more potent anti-proliferative activity
      against EGF- and neuregulin-stimulated SK-OV-3 cells versus serum-stimulated
      cells, accompanied by apparent induction of apoptosis. Finally, TKI-28 was found
      to possess anti-angiogenic effects, characterized by inhibition of cell
      proliferation driven by EGF, VEGF and PDGF, as well as decreased cell migration
      and tube formation in HMECs. These results collectively highlight the
      pharmacological characteristics of TKI-28 as a broad-spectrum tyrosine kinase
      inhibitor, suggesting that it has great potential as an anti-cancer and anti
      angiogenesis agent.

PMID- 16096369
TI  - High frequency somatic mutations in RASSF1A in nasopharyngeal carcinoma.
AB  - High frequency loss of 3p21.3 region is a common event in various kinds of tumors
      including nasopharyngeal carcinoma (NPC). RASSF1A has been identified as a
      putative tumor suppressor gene residing in this region. Chromosome alterations
      and epigenetic changes are commonly observed as mechanisms for inactivation of
      RASSF1A function. In this study, we applied the PCR-cloning-sequencing strategy
      to examine somatic mutations in RASSF1A in NPC tissues as compared with the
      sequences detected in the matched peripheral blood lymphocytes. Our results
      revealed a high incidence of RASSF1A mutation in primary tumor tissues of NPC.
      There are totally 35 mutations identified in 74% (17/23) of these NPC cases,
      including 30 transitions, three transversions and two deletions. Most of these
      mutations result in amino acid changes: three nonsense (stop codon) mutations,
      two-1 bp deletion (frameshift), 26 missense and the remaining four are synonymous
      (silent). No obvious 'hot-spot' mutations were observed in this study. A
      similarly high rate (74%) of promoter methylation of RASSF1A was also detected in
      the same group of NPC tissues, but no significant correlation between mutation
      and methylation was detected. Our results suggest various mechanisms involved in
      inactivation of RASSF1A function and indicate a critical role of RASSF1A in NPC
      development.

PMID- 16096370
TI  - Histone deacetylase inhibitors modulate renal cell carcinoma sensitivity to
      TRAIL/Apo-2L-induced apoptosis by enhancing TRAIL-R2 expression.
AB  - Every year, 12,000 people in the U.S. die from renal cell carcinoma. Current
      therapies include partial or complete nephrectomy or treatments such as
      administration of IFN-alpha and/or interleukins that are moderately effective, at
      best. Moreover, the current therapies are invasive and inefficient and new
      therapies are needed. Histone deacetylase (HDAC) inhibitors have recently been
      found to sensitize cells to apoptosis-inducing agents, although the mechanism of
      this action is largely unknown. The current study has investigated the potential
      of using five different histone deacetylase inhibitors (HDACI) (depsipeptide, MS
      275, oxamflatin, sodium butyrate, and trichostatin A) to sensitize TNF-related
      apoptosis-inducing ligand (TRAIL)/Apo-2L-resistant renal cell carcinoma cells to
      TRAIL/Apo-2L-induced apoptosis. Sodium butyrate and trichostatin A each enhanced
      TRAIL/Apo-2L-mediated tumor cell death to a greater extent than the other HDACI.
      Annexin V staining and caspase activity demonstrated the mechanism of cell death
      was apoptosis. Both sodium butyrate and trichostatin A treatment also increased
      mRNA and surface expression of TRAIL receptor 2 that was dependent on the
      transcription factor Sp1, thus providing a possible mechanism behind the
      increased sensitivity to TRAIL/Apo-2L. These results indicate that combination
      therapy of HDACI, such as sodium butyrate and trichostatin A, and TRAIL/Apo-2L
      has great potential for an efficient alternative therapy for renal cell
      carcinoma.

PMID- 16096371
TI  - Topoisomerase II suppresses the temperature sensitivity of Saccharomyces
      cerevisiae pds5 mutants, but not the defect in sister chromatid cohesion.
AB  - Sister chromatid cohesion enables chromosomes to achieve bipolar attachment to
      the mitotic spindle and its dissolution is required for chromosome segregation.
      The cohesin complex serves as the primary molecular glue responsible for
      cohesion. Pds5p binds to the same chromosomal loci as the cohesin complex but
      plays a distinct role as a regulator of cohesion maintenance. Catenation between
      sister chromatids must also be removed by Topoisomerase II (Top2p) enzymatic
      activity to enable chromosome segregation. We identified TOP2 as a high-copy
      suppressor of the temperature sensitivity of pds5 mutants. TOP2 suppression is
      specific for pds5 mutants as it does not suppress mutants in the cohesin complex.
      TOP2 suppresses mini-chromosome loss in pds5 mutants indicating that it rescues a
      chromosome segregation defect. Surprisingly, TOP2 overexpression fails to
      suppress the cohesion defect of pds5 mutants, suggesting that it suppresses an
      additional and as yet uncharacterized defect in pds5 mutants that is essential
      for viability. A catalytically dead TOP2 allele suppresses pds5 temperature
      sensitivity, suggesting that suppression is unrelated to Top2p enzymatic
      function. Consistent with this idea, when the pds5 mutant is combined with the
      top2-4 mutant, which accumulates DNA catenanes due to defective enzymatic
      activity, the double mutants exhibit synthetic sickness indicating that increased
      catenation is toxic to pds5 cells. Our results suggest that Pds5p and Top2p
      cooperate to promote proper chromosome segregation by a mechanism unrelated to
      either cohesion or catenation/decatenation.

PMID- 16096372
TI  - The role of CREB as a proto-oncogene in hematopoiesis.
AB  - Cyclic-AMP response element binding protein (CREB) is a transcription factor that
      functions in glucose homeostasis, growth-factor- dependent cell survival,
      proliferation and memory. Signaling by hematopoietic growth factors, such as GM
      CSF, results in activation of CREB and upregulation of CREB target genes. Data
      from our laboratory shows that a majority of patients with acute lymphoid and
      myeloid leukemia overexpress CREB in the bone marrow. CREB overexpression is
      associated with poor initial outcome of clinical disease in AML patients. To
      study its role in hematopoiesis, we overexpressed CREB in leukemia cell lines and
      in mice. CREB overexpression resulted in increased survival and proliferation of
      myeloid cells and blast-transformation of bone marrow progenitor cells from
      transgenic mice expressing CREB in the myeloid lineage. CREB transgenic mice also
      develop myeloproliferative disease after one year. Thus, CREB acts as a proto
      oncogene to regulate hematopoiesis and contributes to the leukemia phenotype. Our
      results suggest that CREB-dependent pathways may serve as targets for directed
      therapies in leukemia in the future.

PMID- 16096373
TI  - MicroRNAs: critical regulators of development, cellular physiology and
      malignancy.
AB  - MicroRNAs (miRNAs) are 18-24 nucleotide RNA molecules that regulate the stability
      or translational efficiency of target mRNAs. These regulatory RNAs function by
      acting as sequence-specific guides which recruit a large protein complex known as
      the RNA-induced silencing complex, or RISC, to target mRNAs which are
      subsequently silenced. Diverse functions have been attributed to miRNAs including
      the regulation of cellular differentiation, proliferation, and apoptosis.
      Moreover, significant evidence has accumulated implicating a fundamental role for
      miRNAs in the development of cancer. We recently demonstrated that the oncogenic
      transcription factor c-Myc regulates a group of miRNAs known as the mir-17
      cluster. This represents the first documented example of a mammalian
      transcription factor that regulates miRNA expression. Moreover, it was
      independently demonstrated that the mir-17 cluster accelerates c-Myc-induced
      lymphomagenesis in an in vivo mouse model. Together, these studies support an
      important role for this group of miRNAs in c-Myc-mediated tumorigenesis. We have
      also demonstrated that two miRNAs in this cluster regulate the pro-proliferative,
      pro-apoptotic transcription factor E2F1. Herein, we propose a model in which the
      mir-17 cluster prevents excessive E2F1 activity, and thereby apoptosis, in
      response to activation of c-Myc.

PMID- 16096374
TI  - Regulation of HIF by prolyl hydroxylases: recruitment of the candidate tumor
      suppressor protein ING4.
AB  - Many cellular responses to changes in O2 availability are mediated through the
      hypoxia inducible transcription factor, HIF. HIF regulation is largely dependent
      on the activity of O2-dependent prolyl hydroxylases. Under normoxic conditions,
      these enzymes modify HIF to promote its proteasomal degradation. Recently we
      proposed a second function for the HIF prolyl hydroxylases--recruitment of the
      candidate tumor suppressor protein ING4 to HIF under hypoxic conditions. Rather
      than affecting hydroxylase activity or HIF stability, ING4 mediates the ability
      of HIF to activate transcription of its downstream target genes. This additional
      mechanism of HIF regulation may serve to fine-tune the magnitude of the cellular
      hypoxic response under physiological conditions. Furthermore, the identification
      of a link between ING4 and HIF may shed light on a mechanism by which
      misregulation of ING4 in tumors promotes angiogenesis, loss of contact
      inhibition, and changes in cellular proliferation and survival.

PMID- 16096375
TI  - Apoptosis through targeted activation of caspase 8 ("ATTAC-mice"): novel mouse
      models of inducible and reversible tissue ablation.
AB  - Recent studies identifying obesity as a significant and increasingly more common
      cause of morbidity and mortality have intensified research efforts aimed at
      increasing our understanding of adipose tissue biology. These efforts have
      culminated in the discovery of several adipokines, or adipose tissue-derived
      hormones, that have been implicated in the regulation of multiple physiological
      functions, as well as the realization that adipose tissue dysfunction plays an
      important role in the pathogenesis of diseases such as obesity and diabetes. To
      better understand the role of adipose tissue in these physiological/pathological
      events, several studies have employed transgenic strategies to eliminate adipose
      tissue. However, these mouse models of congenital lipoatrophy/lipodystrophy
      exhibit severe metabolic and somatic cell dysfunction. To circumvent this
      limitation, we have designed and characterized the first inducible fatless mouse.
      The FAT-ATTAC mouse is a transgenic model whereby expression of a myristoylated
      caspase 8-FKBP fusion protein enables selective ablation of adipocytes via
      induction of apoptosis that occurs upon treatment with a chemical dimerizer. The
      FAT-ATTAC mouse model not only has the advantage that adipocyte ablation be
      induced at any time during development, but it is also fully reversible, as
      adipose tissue regenerates after cessation of dimerizer treatment. The
      inducibility of this fatless mouse model holds potential for revealing novel
      physiological roles for adipose tissue as well as its contribution to the
      etiology and pathogenesis of various disease states. Here we describe several
      ongoing areas of research employing the FAT-ATTAC mouse; in addition we describe
      potential uses of the targeted transgenic apoptotic approach to study other cell
      types of interest.

PMID- 16096376
TI  - Increased protein expression of the PTEN tumor suppressor in the presence of
      constitutively active Notch-1.
AB  - Mammalian Notch-1 is part of an evolutionarily conserved family of transmembrane
      receptors best known for involvement in cell fate decisions. Mutations that
      result in Notch-1 activation result in T-lineage oncogenesis. In other cell
      lineages, however, studies have indicated that cooperation with cellular
      signaling pathways, such as Ras, is necessary for Notch-mediated oncogenesis and
      in some settings, Notch-1 has been reported to function as a tumor suppressor. In
      order to test the hypothesis that the Notch-1 pathway exhibits cross-talk with
      Ras/Raf/MEK/ERK, the constitutively active cytoplasmic portion of Notch-1 was
      introduced into 293 HEK fibroblasts via retroviral transduction. ERK-1,-2
      activation was markedly increased in cells expressing constitutively active Notch
      1. These cells exhibited a more rounded morphology as compared to 293 cells
      transduced with an empty vector or parental 293 cells. These observations
      correlated with decreased total and phosphorylated focal adhesion kinase protein
      (FAK). Subsequent examination of phosphatase and tensin homolog deleted on
      chromosome 10 (PTEN) revealed that total and phosphorylated PTEN protein was
      elevated in cells expressing constitutively active Notch-1. Loss of Akt
      phosphorylation was also observed in cells bearing activated Notch-1. Two
      potential binding sites for the Notch effector CBF-1 were identified in the human
      PTEN promoter sequence. A PTEN promoter luciferase reporter exhibited increased
      activity in the presence of Notch-1 signaling. These data indicate that Notch-1
      can participate in cross-talk with other signaling pathways such as
      Ras/Raf/MEK/ERK through the regulation of the PTEN tumor suppressor.

PMID- 16096377
TI  - Analysis of BRAF mutation in primary and metastatic melanoma.
AB  - Mutation of BRAF has been proposed to contribute to melanoma development.
      However, it remains unclear whether or not BRAF mutation is associated with any
      particular stage of melanoma progression. Tumor biopsy specimens from patients
      with melanoma were analyzed to determine whether the frequency of BRAF mutation
      in metastatic melanoma differed from primary melanoma. BRAF mutation was present
      in 15 of 23 (61%) patients with primary melanoma and in 7 of 12 (58%) patients
      with metastatic melanoma. These results suggest that BRAF mutation in melanoma is
      most likely to occur prior to the development of metastatic disease.

PMID- 16096378
TI  - Making trauma education real.
AB  - Human patient simulators can mimic various conditions and respond realistically
      to interventions, helping clinicians perfect their skills and learn from their
      mistakes.

PMID- 16096379
TI  - Radiographic correlation in orthopedic pathology.
AB  - Radiographic correlation is an essential adjunct for the accurate diagnosis of
      orthopedic lesions, yet it is a skill neglected by pathologists. The purpose of
      this review is to demonstrate why performing this correlation is an essential
      part of the diagnostic process and not merely an interesting adjunct to the
      surgical pathology of orthopedic lesions. The relationships between x-rays and
      tissues are explored with an emphasis on bone and soft tissue composition and
      structure. In addition, the rudiments of complementary imaging studies and how to
      incorporate their data into diagnoses are examined.

PMID- 16096380
TI  - Molecular diagnostics in central nervous system tumors.
AB  - Central nervous system (CNS) neoplasms can be diagnostically challenging, due to
      remarkably wide ranges in histologic appearance, biologic behavior, and
      therapeutic approach. Nevertheless, accurate diagnosis is the critical first step
      in providing optimal patient care. As with other oncology-based specialties,
      there is a rapidly expanding interest and enthusiasm for identifying and
      utilizing new biomarkers to enhance the day-to-day practice of surgical
      neuropathology. In this regard, the field is primed by recent advances in basic
      research, elucidating the molecular mechanisms of tumorigenesis and progression
      in the most common adult and pediatric brain tumors. Thus far, few have made the
      transition into routine clinical practice, the most notable example being 1p and
      19q testing in oligodendroglial tumors. However, the field is rapidly evolving
      and many other biomarkers are likely to emerge as useful ancillary diagnostic,
      prognostic, or therapeutic aids. The goal of this article is to highlight the
      most common genetic alterations currently implicated in CNS tumors, focusing most
      on those that are either already in common use in ancillary molecular diagnostics
      testing or are likely to become so in the near future.

PMID- 16096381
TI  - Use and abuse of lung biopsy.
AB  - The lung biopsy is widely recognized as a valuable tool for the diagnosis and
      management of diverse pulmonary disorders. The transbronchial lung biopsy, open
      lung biopsy, and video assisted thoracoscopic surgery biopsy are the principal
      tools that have been developed for obtaining lung tissue for histopathological
      examination. Whereas these various types of lung biopsies are highly sensitive
      and specific tests available for diagnosis, they may be fraught with potential
      problems. This review hopes to inform the reader of the indications and
      limitations of the lung biopsy.

PMID- 16096382
TI  - Atypical forms of microscopic colitis: morphological features and review of the
      literature.
AB  - Microscopic colitis is defined as a syndrome of chronic watery diarrhea with a
      chronic inflammatory cell infiltrate in the colonic mucosa but without
      significant abnormalities at colonoscopy. It encompasses at least two
      histopathologic entities (ie, collagenous and lymphocytic colitis). The
      recognition and characterization of microscopic colitis has markedly changed the
      approach to the evaluation and management of chronic diarrhea. The histologic
      features of collagenous and lymphocytic colitis are well known to most
      pathologists. By considering the clinical history and symptoms, the pathologist
      should be able to reach the correct diagnosis in most cases. However, the
      spectrum of morphologic changes associated with watery diarrhea syndrome appears
      to be broader than originally thought. Morphologic changes more often associated
      with chronic inflammatory bowel disease or even chronic ischemic or infectious
      colitis have been noted in patients with clinically established microscopic
      colitis. The data presented in this article suggest that microscopic colitis is a
      heterogeneous entity, which includes both classic and "atypical" forms. Problems
      arise when cases do not fit the usual pattern or lack some of the findings that
      are expected. Pathologists should be aware of the presence of atypical forms of
      microscopic colitis.

PMID- 16096383
TI  - Ewing sarcoma family of tumors.
AB  - The Ewing sarcoma family of tumors (ESFT) comprises morphologically heterogeneous
      tumors that are characterized by nonrandom chromosomal translocations involving
      the EWS gene and one of several members of the ETS family of transcription
      factors. The translocation t(11;22)(q24;q12) is the most common and leads to the
      formation of the EWS-FLI1 fusion protein, which contributes to ESFT pathogenesis
      by modulating the expression of target genes. Tumors may be composed of small
      uniform cells with minimal morphologic evidence of differentiation, or they may
      be composed of larger, less uniform cells with varying degrees of neuroectodermal
      differentiation. CD99 expression is identified in nearly all ESFT and constitutes
      a useful positive marker when used as part of a panel of immunostains that can
      help rule out other differential diagnostic considerations. Molecular diagnostic
      tests commonly used to detect the presence of ESFT-specific translocations
      include RT-PCR and fluorescence in situ hybridization. Current therapy for
      patients with ESFT includes chemotherapy and surgery with or without radiation
      therapy. At present, the most significant prognostic factor for patients with
      ESFT is whether the disease is localized or metastatic.

PMID- 16096384
TI  - Update on post-liver transplantation infections, malignancies, and surgical
      complications.
AB  - Complications of liver transplantation are not limited to acute and chronic
      rejection, and recurrence of original disease, but include surgical
      complications, most commonly hepatic artery occlusion, infections, and
      development of de novo malignancies. In the early posttransplantation period,
      procurement/preservation injury, non-immunologic injury to the graft during
      harvesting and implantation, is manifested by centrilobular hepatocyte pallor and
      cholestasis but rarely leads to significant graft dysfunction. Ischemic
      complications, such as hepatic artery thrombosis, are more serious complications
      and may lead to early graft loss or biliary stricture. Infectious complications
      generally occur in the mid-to-late period after transplantation; cytomegalovirus
      (CMV) remains a common pathogen. Human herpes 6 virus infection has been
      implicated in allograft dysfunction, but is usually seen in the setting of co
      infection with CMV. De novo malignancies are emerging as a significant cause of
      mortality after liver transplantation; risk is cumulative, and increases with
      time posttransplantation. Development of such malignancies in the setting of
      solid organ transplantation is multifactorial, and is related to individual and
      regional predispositions to malignancy, pre-transplantation disease states,
      recipient viral status, and use and intensity of immunosuppression regimens.

PMID- 16096385
TI  - AMR series unilateral (localized) renal cystic disease.

PMID- 16096393
TI  - Treatment of elevated homocysteine to restore normal wound healing: a possible
      relationship between homocysteine, nitric oxide, and wound repair.

PMID- 16096394
TI  - Where's the protein?

PMID- 16096395
TI  - CERT program reviews Medicare contractors and providers.

PMID- 16096396
TI  - Adapting national and international leg ulcer practice guidelines for local use:
      the Ontario Leg Ulcer Community Care Protocol.
AB  - BACKGROUND: Because of growing resources devoted to individuals requiring
      community care for leg ulcers, the authority responsible for home care in Ottawa,
      Ontario, Canada, established and evaluated a demonstration leg ulcer service. In
      an effort to provide current and evidence-based care, existing leg ulcer clinical
      practice guidelines were identified and appraised for quality and suitability to
      the new service. PROCESS: The Practice Guideline Evaluation and Adaptation Cycle
      guided development of a local protocol for leg ulcer care, which included: (1)
      systematically searching for practice guidelines, (2) appraising the quality of
      identified guidelines using a validated guideline appraisal instrument, (3)
      conducting a content analysis of guideline recommendations, (4) selecting
      recommendations to include in the local protocol, and (5) obtaining practitioner
      and external expert feedback on the proposed protocol. Updating the protocol
      followed a similar process. RESULTS: Of 19 identified leg ulcer practice
      guidelines, 14 were not evaluated because they did not meet the criteria (ie,
      treatment-focused guidelines, written in English and developed after 1998). Of
      the 5 remaining guidelines, 3 were fairly well developed and made similar
      recommendations. The level of evidence supporting specific recommendations ranged
      from randomized clinical trial evidence to expert opinion. By comparing the
      methodologic quality and content of the guidelines, the Task Force reached
      consensus regarding recommendations appropriate for local application. Two
      additional guidelines were subsequently identified and incorporated into the
      local protocol during a scheduled update. CONCLUSIONS: Local adaptation of
      international and national guidelines is feasible following facilitation of the
      Practice Guidelines Evaluation and Adaptation Cycle.

PMID- 16096397
TI  - Preventing and managing surgical wound dehiscence.

PMID- 16096398
TI  - Pathophysiology and current management of burn injury.
AB  - PURPOSE: To provide the physician and registered professional nurse with an
      overview of the pathophysiology and current management of burn injuries. TARGET
      AUDIENCE: This continuing education activity is intended for physicians and
      nurses with an interest in learning about evidence-based prevention and
      management of burn wounds. OBJECTIVES: After reading the article and taking the
      test, the participant should be able to: (1) Explain the pathophysiology of skin
      function. (2) Describe the different types of burn injuries. (3) Identify the
      treatment strategies for burn injuries.

PMID- 16096400
TI  - Assessment of HER-2 status in pancreatic adenocarcinoma: correlation of
      immunohistochemistry, quantitative real-time RT-PCR, and FISH with aneuploidy and
      survival.
AB  - HER-2 is a transmembrane growth factor receptor recognized in overexpression as
      an independent adverse prognostic factor in several cancers. This study measured
      HER-2 overexpression in pancreatic adenocarcinoma at the genetic,
      transcriptional, and translational level. Expression was gauged with regard to
      stage, grade, and survival. Pancreatic adenocarcinoma samples (n = 30) were
      analyzed with immunohistochemical labeling for HER-2 protein, Quantitative real
      time reverse transcriptase polymerase chain reaction (Q-RT-PCR) measurement of
      HER-2 mRNA and fluorescence in situ hybridization (FISH) analysis of HER-2 gene
      expression. HER-2 expression in benign pancreatic lesions (n = 10) provided a
      control. Five (17%) of the pancreatic adenocarcinomas scored maximal 3+
      immunohistochemistry (IHC) labeling, seven (23%) had significantly increased
      expression of HER-2 mRNA, while only one (3%) exhibited low level HER-2 gene
      amplification. Ten (33%) tumors demonstrated aneuploidy. In general, concordance
      between methodologies was poor, but the best agreement was seen between FISH
      aneuploidy status and Q-RT-PCR mRNA overexpression (80% agreement), followed by
      IHC and Q-RT-PCR (73% agreement). The least agreement was seen between IHC and
      FISH aneuploidy status (67% agreement). Tumor stage was positively associated
      with HER-2 mRNA and protein expression, but tumor grade and other patient
      characteristics did not reach statistical significance. A poor survival outcome
      was demonstrated with positive HER-2 status in all three measures of
      overexpression (Kaplan-Meier log-rank score; P < 0.01 [IHC], P = 0.05 [Q-RT-PCR],
      P = 0.02 [FISH]). Discordance in expression at the nuclear, cytoplasmic, and cell
      surface levels highlights the limitations of immunohistochemical evaluation alone
      and stresses the need for further evaluation of response to anti-HER-2 targeted
      therapies in tumors displaying overexpression in gene copy, mRNA, and receptor
      protein.

PMID- 16096401
TI  - Clinical relevance of occult tumor cells in lymph nodes from gastric cancer
      patients.
AB  - The current method for staging in gastric cancer is not sufficient as even after
      a complete primary tumor resection, patients with node-negative gastric cancer
      suffer from disease recurrence. In this study, the relation between disease
      recurrence and the presence of occult tumor cells (OTC) in lymph nodes from
      gastric cancer patients was evaluated. In a case-control design, lymph nodes from
      40 cases (disease recurrence) and 41 controls (no disease recurrence and followed
      for at least five years) with gastric cancer were examined for the presence of
      OTC, that comprised micrometastases (MM; >0.2 mm and < or =2.0 mm) and isolated
      tumor cells (ITC; < or =0.2 mm). The original hematoxylin and eosin-stained
      sections of all lymph nodes from cases and controls were previously considered as
      tumor-negative by the local pathologist. Fresh hematoxylin and eosin-stained
      sections were screened by conventional microscopy. Histologic sections stained by
      immunohistochemistry with anticytokeratin antibodies CAM5.2 were screened by
      conventional and automated microscopy. Tumor cells were detected in lymph nodes
      from 40 of 81 (49%) patients. There was no significant difference in the presence
      of OTC, MM, or ITC between the case and control groups (P = 0.658, P = 0.691, P =
      0.887, respectively). However, significantly more cases presented with 20% or
      more OTC-positive lymph nodes (P = 0.015). A multivariate logistic regression
      analysis showed that examination of less than five lymph nodes (odds ratio, 13.8;
      95% confidence interval, 1.6-120.6, P = 0.018) was the only significant
      independent risk factor for disease recurrence, especially for locoregional
      disease recurrence (odds ratio, 20.4; 95% confidence interval, 2.2-190.8, P =
      0.008). A similar analysis for distant disease recurrence showed a percentage of
      20% or more OTC-positive lymph nodes to be the only significant independent risk
      factor (odds ratio, 15.6, 95% confidence interval, 1.6-151.4, P = 0.018). The
      sensitivity of immunohistochemistry evaluated by microscopy to identify cases
      with 20% or more OTC-positive lymph nodes increased from 8% for conventional
      microscopy to 22% for automated microscopy (McNemar's test, P = 0.063). The mere
      presence of OTC-positive lymph nodes in gastric cancer patients did not predict
      disease recurrence. However, the number of examined lymph nodes and the
      percentage of OTC-positive lymph nodes were independent risk factors for
      locoregional disease recurrence and distant disease recurrence, respectively.
      Automated microscopy was essential in identifying patients with 20% or more OTC
      positive lymph nodes. Therefore, a maximum number of lymph nodes should be
      removed and meticulously examined for OTC to identify high-risk patients. These
      patients should be considered for additional treatment.

PMID- 16096402
TI  - Analysis of mutations in B-RAF, N-RAS, and H-RAS genes in the differential
      diagnosis of Spitz nevus and spitzoid melanoma.
AB  - A definite diagnosis cannot be established based on histologic features alone in
      a large number of Spitz nevi and spitzoid melanomas. In a vast majority of common
      benign and malignant melanocytic lesions, B-RAF and N-RAS mutations were
      described, but these were not detected in Spitz nevi. In contrast, H-RAS
      mutations were frequently encountered in Spitz nevi, but only rarely in
      melanomas. To date, B-RAF mutation analysis has not been reported in atypical
      Spitz nevi, and there are only a few reports of it in spitzoid melanomas. We
      analyzed 96 formalin-fixed, paraffin-embedded spitzoid melanocytic lesions for
      hotspot mutations in B-RAF, N-RAS, and H-RAS genes to test the assumption whether
      mutation analysis would assist a more accurate diagnosis of spitzoid melanocytic
      lesions, which are notoriously difficult to classify. B-RAF or N-RAS mutations
      were observed in 31 of 36 (86%) spitzoid melanomas, and in 6 of 7 (86%) spitzoid
      melanoma metastases. In contrast, none of the 14 Spitz nevi and none of the 16
      atypical Spitz nevi had mutations in any of the three genes. A B-RAF or N-RAS
      mutation was found in 8 of 23 (35%) spitzoid lesions suspected for melanoma. H
      RAS mutations were detected in 4 of 14 (29%) Spitz nevi, in 3 of 22 (14%)
      atypical Spitz nevi, in 1 of 15 (7%) spitzoid tumors suspected for melanoma, but
      in none of the spitzoid melanomas. These results strongly indicate that Spitz
      nevi and spitzoid melanomas are genetically unrelated entities. Furthermore, we
      can conclude that mutation analysis may be useful as an additional diagnostic
      tool to distinguish between benign and malignant spitzoid lesions.

PMID- 16096403
TI  - Sarcomatoid carcinoma of the penis: a clinicopathologic study of 15 cases.
AB  - Sarcomatoid carcinomas are uncommon, high-grade tumors, predominantly composed of
      spindle cells. Only a few cases arising in the penis have been reported. The aim
      of this study is to better define the clinicopathologic features of this
      neoplasm. A total of 400 cases of squamous cell carcinoma of the penis were
      reviewed from which 15 sarcomatoid carcinomas (4%) were identified. Clinical and
      pathologic features were evaluated in all cases. Immunohistochemical studies for
      expression of AE1/AE3, Cam 5.2, 34betaE12, EMA, vimentin, muscle specific actin,
      smooth muscle actin, desmin, S-100, p63, and p53 and in situ hybridization
      studies for HPV were performed in 5 cases. Information about lymph node status
      was available in 9 cases, and follow-up in 5 cases. The mean age was 59 years,
      and mean tumor size was 5 cm. Grossly, most tumors were large, polypoid, and
      ulcerated masses frequently affecting the glans (93%) and deeply invading corpora
      cavernosa (80%) and skin. Microscopically, the lesions were predominantly
      composed of atypical spindle cells disposed in interlacing fascicles, resembling
      fibrosarcoma or leiomyosarcoma, sometimes admixed with pleomorphic giant cells
      mimicking malignant fibrous histiocytoma. One case was predominantly composed of
      myxoid areas. Less frequent and focal patterns were pseudoangiomatous and
      epithelioid. Mitotic figures were numerous, and necrosis was prominent. Foci of
      heterologous differentiation toward bone (osteosarcomatous component) were
      present in 1 case. Four cases showed a minor mixed component of usual, papillary,
      verrucous, and basaloid carcinoma. Intrapenile metastasis ("satellitosis") was
      present in 4 tumors. One of the cases was multicentric with a separate
      independent focus of well-differentiated carcinoma with pseudohyperplastic
      features. Associated low- and high-grade squamous intraepithelial lesions were
      noted in 73% of the cases. Immunohistochemical studies and HPV in situ
      hybridization were done in 5 cases. The spindle cells were diffusely positive for
      vimentin and p53 and showed at least intermediate expression of 34betaE12 and p63
      in all cases. EMA and AE1/AE3 were focally positive in 60% of the cases, and Cam
      5.2 was focally positive in 1 case. Tumor cells failed to express muscle specific
      actin, smooth muscle actin, desmin, and S-100. HPV in situ hybridization was
      negative in all cases. Inguinal metastases were present in 89% of the cases. Two
      of five patients with adequate follow-up died of disease within 8 months of the
      diagnoses. In conclusion, penile sarcomatoid carcinomas are unusual, large, and
      aggressive tumors usually associated with lymph node metastasis and poor outcome.
      Differential diagnoses include sarcoma and melanoma. Cytokeratin 34betaE12 and
      p63 appear to be the more specific and sensitive markers to categorize these
      tumors as epithelial. Diffuse immunoreactivity for p53, compared with a more
      basal and focal reactivity in differentiated squamous cell carcinoma, may be
      indicative of a late mutation in the natural progression of the disease.

PMID- 16096404
TI  - Perineural involvement by benign prostatic glands on needle biopsy.
AB  - Uncommonly, benign prostatic glands can be seen in the perineural space, known as
      "benign perineural involvement." This phenomenon has not been specifically
      studied on needle biopsies; 27 needle biopsy cases with perineural involvement
      were evaluated; 22 (81.4%) were received in consultation, while 5 (18.5%) were in
      house cases. In 15 of 22 (68.2%) consult cases, a question was raised by the
      submitting pathologist regarding the focus. The following patterns of perineural
      involvement were observed: indentation 14 (51.8%) cases, by up to 3 glands;
      tracking 8 (29.6%) cases, by up to 6 glands; wrapping 7 (25.9%) from one half to
      three fourths around the nerve, by up to 3 glands, 1 case showed 95% wrapping;
      intraneural 4 (14.8%) cases by up to 3 glands; adjacent 2 (7.4%) cases by up to 2
      glands. Partial atrophy in the involved glands was seen in 10 (38.4%) cases and
      complete atrophy in 6 (23%). Of 8 cases with the lesion still present on slides
      for immunohistochemistry, high molecular weight cytokeratin (HMWCK) and p63 were
      positive in 6 (75%) and negative in the 2 (25%) cases with partial atrophy. A
      total of 6 (27%) cases had more than one pattern of perineural involvement. On
      hematoxylin and eosin sections, basal cells were not identified in 12 (46%)
      cases, including 2 negative and 1 positive cases stained for HMWCK. Patterns most
      closely mimicking cancer included intraneural and incomplete perineural
      encirclement. Perineural invasion by benign atrophic glands cause diagnostic
      difficulty, especially with negative HMWCK. Careful attention to hematoxylin and
      eosin morphology and comparison of perineural involvement to adjacent and distant
      benign glands are necessary.

PMID- 16096405
TI  - Cytogenetic aberrations in perineurioma: variation with subtype.
AB  - Only two karyotypes of perineurioma have previously been reported,
      46XX,del(10)(q22q24),der(10),del(22)(q11-12q?)/47, idem,+der(10) (in a sclerosing
      perineurioma of the finger) and 45,XX,add(14)(p13),-22,add(22)(q11.2) (in an
      intraneural perineurioma). We investigated the clinicopathologic and cytogenetic
      findings in four consecutive perineuriomas in children, including two small (< or
      =1 cm) digital sclerosing perineuriomas, a 2-cm intraneural perineurioma, and a
      16-cm abdominal soft tissue perineurioma. All lesions showed plump perineurial
      cells in a complex whorled configuration. Immunohistochemical (strong EMA
      immunostaining in all cases) and ultrastructural (in three of three lesions
      examined) evidence of perineurial differentiation was present. The sclerosing
      perineuriomas showed 46,XY,t(2;10)(p23;q24) and 47,XX,add(3)(q23),add(6)(q21),-5,
      9,-10,-22,+mar1,+mar2,+mars; the intraneural tumor showed
      46,XX,add(2)(q11.2),add(3)(q12); and the abdominal soft tissue perineurioma
      showed 46,XX,t(8;9)(q13;q22). Metaphase FISH analysis for an ALK gene
      rearrangement in the sclerosing perineurioma with t(2;10) was negative; the ALK
      signal remained on the der(2). We conclude that perineuriomas display mostly
      simple karyotypes, characterized by one or few chromosomal rearrangements or
      numerical changes. In conjunction with the previously published sclerosing
      perineurioma karyotypes, the findings of chromosome 10 aberrations,
      t(2;10)(p23;q24) and monosomy 10 in two sclerosing perineuriomas, indicate that
      rearrangements and/or deletions of 10q are a consistent finding in this variant
      of perineurioma. The findings also expand previous assertions that chromosome 22
      abnormalities are pathogenetic in perineurioma and suggest that diverse genetic
      tumorigenic mechanisms may exist, possibly depending on the subtype.

PMID- 16096406
TI  - NF1-associated gastrointestinal stromal tumors have unique clinical, phenotypic,
      and genotypic characteristics.
AB  - Gastrointestinal stromal tumors (GIST) have been reported to occasionally occur
      in patients with neurofibromatosis type 1 (NF1). This study aims to describe the
      phenotypic and genotypic characteristics of GIST in NF1 patients and attempts to
      elucidate the relationship between them. We analyzed GIST arising in 15 NF1
      patients (8 males and 7 females, 19-82 years of age). Eleven patients had
      multiple GISTs (3 to >100 tumors) ranging from 1 mm to 10 cm in size and
      predominantly involving the small intestine including the duodenum. Tumors were
      symptomatic in 8 patients and incidental findings in the remaining 7 patients.
      Microscopically, the tumors cells were typically spindled and the mitotic rate
      low; 9 patients had tumors classified as very low or low risk and 6 as
      intermediate risk GIST. Nine patients were treated surgically and none developed
      metastases or died of disease. Immunohistochemical stains for CD117 were strongly
      positive in 47 of 50 GIST; they also accentuated hyperplastic foci (diffuse and
      focal) of the interstitial cells of Cajal that were often associated with
      microscopic GIST in the surrounding intestinal muscle wall. No KIT or PDGFRA
      mutations were detected in 24 GIST from 12 patients using dHPLC analysis and DNA
      sequencing. We conclude that patients with NF1 have a high risk of developing
      GIST. NF1-associated GIST are also phenotypically and genotypically distinct from
      sporadic GIST, indicating that different pathogenetic mechanisms are involved in
      their evolution.

PMID- 16096407
TI  - The number of metastatic lymph nodes in extrahepatic bile duct carcinoma as a
      prognostic factor.
AB  - The number of lymph nodes with metastases is known to be an important prognostic
      factor in carcinomas of many organs. The insufficient sampling of lymph nodes has
      also been associated with worse outcome in several types of carcinoma. However,
      the prognostic significance of lymph node dissection is not well characterized in
      extrahepatic bile duct (EBD) carcinomas. For 209 patients with EBD carcinoma, the
      total number of retrieved lymph nodes and the number of metastatic lymph nodes
      were evaluated, and other clinicopathologic variables were correlated with
      patient survival. The number of retrieved lymph nodes was not significantly
      correlated with survival in this study. The presence of metastasis to lymph nodes
      significantly decreased survival of patients with EBD carcinoma. The patients
      with 5 or more metastatic lymph nodes had significantly worse survival than those
      with 4 or less metastatic lymph nodes. To evaluate the prognosis of the patients
      with EBD carcinomas more precisely, the number of metastatic lymph nodes as well
      as the status of metastasis to lymph nodes should be examined and reported. Based
      on the present data, we propose that nodal classification should be divided into
      N1 (metastasis in 1 to 4 regional lymph nodes) and N2 (metastasis in 5 or more
      regional lymph nodes).

PMID- 16096408
TI  - Undifferentiated intimal sarcoma of large systemic blood vessels: report of 14
      cases with immunohistochemical profile and review of the literature.
AB  - Intimal sarcoma (IS) is defined as a malignant tumor arising in the tunica intima
      of large blood vessels. In systemic circulation, the majority of IS develop in
      the aorta, where close to three fourths of published cases lack specific
      differentiation and are called undifferentiated intimal sarcomas (UIS). The
      remaining cases are intima-associated sarcomas of recognized types, also called
      differentiated intimal sarcomas (DIS). In this report, we further characterize
      UIS, including its immunohistochemical profile and results of comparative genomic
      hybridization. A total of 14 cases of UIS were collected from 17 medical
      institutions, including slides, blocks, electron photomicrographs, clinical
      abstracts, and reports of surgical pathology specimens and autopsies. The
      patients, 7 women and 7 men, were 41 to 85 years of age (median, 65.6 years).
      Twelve tumors arose from the aorta, one from the left external iliac and femoral
      arteries, and one in a large systemic vein (the venous tumor was included due to
      histologic similarity with the arterial lesions). Tumors ranged from 1 cm to over
      10 cm in diameter. Histopathology was that of a largely necrotic, poorly
      differentiated epithelioid and pleomorphic malignant neoplasm relating to the
      tunica intima. Usually there was only a thin layer of viable tumor cells
      overlying a large thrombus. All tumors stained at least focally with the
      endothelial markers CD31 and Fli-1; however, there was otherwise considerable
      variability in immunophenotype. The distinctive histopathologic appearance of the
      primary luminal lesion was lost whenever tumor invaded outside the vessel wall
      (into adventitia and beyond) or in metastatic sites. Such extravascular tumors
      assumed a variety of patterns reminiscent of undifferentiated pleomorphic sarcoma
      (UPS; in older literature also known as pleomorphic malignant fibrous
      histiocytoma, MFH) or other distinct types of sarcomas, including osteosarcoma,
      angiosarcoma, and rhabdomyosarcoma. The results of comparative genomic
      hybridization were nonspecific. Eleven patients died of the disease, in an
      average of 11 months after diagnosis. Three patients are still alive and free of
      disease at 4, 16, and 27 years. UIS of large systemic vessels represents a
      distinct clinical entity where intraluminal sarcoma presents with thrombosis and
      occlusion of large vessels. It is associated with a highly characteristic,
      although not entirely specific, histology and immunohistochemical phenotype. The
      histogenesis of UIS is not certain; however, it seems that the cell of origin
      must leave the confines of the vessel wall to show altered morphology. Although
      there are rare long-term survivors, UIS behaves as a fully malignant neoplasm
      that is almost uniformly associated with metastases and tumor-related death.

PMID- 16096409
TI  - Pleomorphic pancreatic endocrine neoplasms: a variant commonly confused with
      adenocarcinoma.
AB  - Most pancreatic endocrine neoplasms (PENs) have distinctive endocrine growth
      patterns and uniform nuclear morphology; they are regarded as relatively low
      grade tumors. Significant nuclear pleomorphism is a feature that may raise
      concerns about aggressive behavior or even obscure the endocrine nature of the
      neoplasm. Eight PENs exhibiting marked nuclear pleomorphism (>20% of the tumor
      cells) were identified during a review of 136 PENs (5.9%) from the pathology
      files of Memorial Sloan-Kettering Cancer Center. The histologic,
      immunohistochemical, ultrastructural (4 cases), and clinical features were
      reviewed. There were 6 males and 2 females ranging from 30 to 69 years (mean, 55
      years). The tumors averaged 5.8 cm (range, 1.5-14 cm). Six tumors (75%) were
      initially misdiagnosed in 5 cases as adenocarcinoma and in one as solid
      pseudopapillary tumor; in 2 cases, the misdiagnosis was based on fine needle
      aspiration cytology and in 4 on histologic examination. The architectural
      features of the tumors resembled those of other PENs, but the nuclei were
      markedly enlarged, irregularly shaped, and hyperchromatic, with frequent bizarre
      forms. Cells with pleomorphic nuclei also generally had abundant cytoplasm,
      sometimes with large perinuclear glassy inclusions. The mitotic rate was not
      elevated compared with other PENs, averaging 1.9 (range, 0-7) per 50 high power
      fields. Immunohistochemical findings were (number positive/number stained):
      chromogranin (8 of 8), synaptophysin (7 of 8), progesterone receptor (4 of 7),
      CD99 (2 of 5), S-100 protein (3 of 7), and p53 (0 of 6). Scattered cells
      expressed peptide hormones in a minority of cases. By electron microscopy,
      abundant dense core granules were identified, in some cases embedded within
      perinuclear arrays of intermediate filaments. Six patients underwent curative
      resection; at follow-up, 4 were free of disease at 11, 13, 30, 112 months (mean,
      42 months), 1 developed liver metastases at 77 months and was alive with disease
      at 94 months, and 1 was lost to follow-up. Two patients had unresectable tumors
      and were alive with disease at 10 and 78 months. Striking nuclear pleomorphism
      may occur in otherwise typical PENs and commonly causes difficulties in the
      distinction from adenocarcinoma. There does not appear to be prognostic
      significance to these nuclear changes, and the morphologic features of
      pleomorphic PENs otherwise resemble those of their conventional counterparts.

PMID- 16096410
TI  - High-grade prostatic intraepithelial neoplasia and atypical small acinar
      proliferation: predictive value for cancer in current practice.
AB  - In earlier studies, prostate cancer (PCa) has been reported to appear in 21% to
      48% of subsequent biopsies for isolated high-grade prostatic intraepithelial
      neoplasia (PIN) and in 34% to 60% for isolated atypical small acinar
      proliferation suspicious for, but not diagnostic of, malignancy (ASAP). We report
      results of follow-up biopsies in a recent cohort of community practice patients
      who underwent biopsy for PSA abnormalities. The study group consisted of 336 men
      with initial diagnoses of PIN (n = 204), ASAP (n = 78), or both lesions (n = 54)
      who underwent at least one repeat biopsy. Mean follow-up intervals in months were
      6.0 for PIN, 3.8 for ASAP, and 4.9 for PIN/ASAP. Follow-up PCa detection rates
      were 23%, 37%, and 33%, respectively. The predictive value of ASAP was
      significantly higher than that for PIN (P = 0.0188). In 23 PIN studies with
      chronologic midpoints in the early 1990s, follow-up PCa was detected in a mean of
      36% of cases, whereas this value was 21% after the year 2000. In 13 ASAP studies,
      mean PCa detection on follow-up was 45% until 1996 and 39% from 1997 to present.
      PIN/ASAP predicted PCa in 33% of cases in our study, similar to ASAP alone (P =
      0.65) and had a mean predictive value of 44% in the literature. Factors that may
      account for the decline in PIN predictive values include: 1) extended biopsy
      techniques that yield higher rates of initial cancer detection, 2) lower
      detection rate for the remaining small cancers that may accompany PIN, and 3)
      remaining PIN cases may lack concomitant cancer.

PMID- 16096411
TI  - Thymoma arising within cardiac myxoma.
AB  - Hematopoietic, glandular, and mesenchymal elements can be found within cardiac
      myxomas; ectopic endocrine tissues and "thymic rests" have also rarely been
      described. Atrial tumors (one right and one left) from 2 patients (a 69-year-old
      man and a 77-year-old woman) were encountered among the atrial myxoma cases in
      one of the author's consultation files. Both tumors were comprised of classic
      cardiac myxoma (with characteristic rings and syncytial chains of myxoma cells in
      a loose myxoid matrix) and cellular thymoma-like elements (characterized by a
      lobulated sheet-like growth of epithelioid spindle cells admixed with small
      lymphocytes punctuated by vessels with prominent perivascular spaces). Neither
      patient had evidence of thymoma elsewhere. Immunophenotypically, the thymoma-like
      component reacted strongly with antibodies to keratins (AE1/AE3, Cam 5.2, wide
      spectrum, CK19, CK7) and CD57 and weakly with antibodies to CD31, CD34, and
      calretinin. This intermediate phenotypic expression of both epithelial and
      vascular antigens likely reflects the multipotential nature of the cells
      comprising this lesion. The most likely explanation for this extremely unusual
      finding is neoplastic transformation of thymic rests within a myxoma.

PMID- 16096412
TI  - Genomic analysis of blue nevi and related dermal melanocytic proliferations.
AB  - Blue nevi are benign dermal melanocytic proliferations that can sometimes share
      overlapping microscopic features with melanoma. We used comparative genomic
      hybridization to analyze three groups of dermal melanocytic proliferations. Group
      1 consisted of 10 cellular blue nevi and 1 deep penetrating nevus, none of which
      showed chromosomal aberrations. Group 2 consisted of 11 lesions that were
      histopathologically ambiguous. Three of these lesions demonstrated chromosomal
      aberrations (three or fewer per lesion). Group 3 consisted of seven
      histopathologically malignant lesions, each showing three or more chromosomal
      aberrations. Moderate to severe cytologic atypia and a mitotic rate of three or
      more mitoses per 10 high power fields were present in six of eight (75%) lesions
      that had at least three chromosomal aberrations but were absent in 15 of 20 (75%)
      lesions without chromosomal aberrations. Necrosis was present in four of the 29
      (13%) lesions, with every lesion with necrosis demonstrating three or more
      genomic abnormalities. In conclusion, histopathologically unequivocally benign or
      malignant dermal melanocytic proliferations show nonoverlapping patterns of
      chromosomal aberrations. Ambiguous lesions can be separated into lesions with and
      without chromosomal aberrations. Future studies with clinical follow-up are
      necessary to determine which aberrations are most informative for classification
      of these lesions.

PMID- 16096413
TI  - The influence of polysomy 17 on HER2 gene and protein expression in
      adenocarcinoma of the breast: a fluorescent in situ hybridization,
      immunohistochemical, and isotopic mRNA in situ hybridization study.
AB  - Breast carcinomas with amplification of HER2 on chromosome 17 are associated with
      HER2 protein overexpression, adversely affecting prognosis and predicting
      response to Herceptin therapy. Chromosome 17 polysomy is encountered in assessing
      HER2 gene status, and its impact on HER2 gene and protein expression remains
      unclear. This impact was investigated in breast carcinomas identified by
      fluorescence in situ hybridization (FISH) to have a gain of chromosome 17
      (CEP17+; n = 56), using a dual probe assay, which detects HER2 gene copy number
      and enumerates chromosome 17 (HER2/CEP17; Vysis). Cases were immunostained for
      HER2 protein (CB-11, Ventana), and scored blinded to FISH. A subgroup was
      evaluated by isotopic in situ hybridization for HER2 mRNA expression. Controls
      included ten HER2 amplified and ten nonamplified tumors, eusomic for chromosome
      17. Immunohistochemistry (IHC) for HER2 protein was negative (0 or 1+) in 69% (39
      of 56), 2+ in 27% (15 of 56), and 3+ in 3% (2 of 56) of CEP17+ cases. The mean
      CEP17 copy number among the three groups was similar (3.1, 3.0, and 3.1 for IHC
      0/1+, 2+, and 3+, respectively). Isotopic in situ hybridization for HER2 mRNA
      performed on 26 CEP17+ cases (16 IHC 0-1+, 10 IHC 2+ or 3+) showed no increased
      HER2 mRNA expression (normalized to beta-actin mRNA). The mRNA expression and the
      IHC staining of the HER2-amplified and nonamplified controls was concordant with
      their FISH status. These results suggest that chromosome 17 polysomy in the
      absence of HER2 amplification does not have a significant biologic influence on
      HER2 gene expression in breast carcinoma.

PMID- 16096414
TI  - The 2005 International Society of Urological Pathology (ISUP) Consensus
      Conference on Gleason Grading of Prostatic Carcinoma.

PMID- 16096415
TI  - Pseudoangiomatous stromal hyperplasia in lesions involving anogenital mammary
      like glands.
AB  - Pseudoangiomatous stromal hyperplasia (PASH), first reported in 1986, is nowadays
      a well-recognized change in the breast. We present three cases of lesions
      involving anogenital mammary-like glands demonstrating this feature. All patients
      were females (ages, 42, 43, and 53 years). Each presented with a solitary, 1.5-
      to 2-cm asymptomatic nodule. Locations included the perianal area, perineum, and
      labium majus. Histopathologically, one lesion was classified as low-grade
      phyllodes tumor, another as fibroadenoma, and in the remaining case PASH was
      found in the background of mild hyperplasia of anogenital mammary-like glands and
      substantial lipomatous metaplasia. In all lesions, PASH had an identical
      appearance to that in the breast, that is open, slit-like, often anastomosing
      channels devoid of erythrocytes and lined by discontinuous, often attenuated,
      inconspicuous cells without atypia or mitotic activity set in a hyalinized
      collagenous stroma. Quantitatively, PASH ranged in the above cases, forming a
      relatively small focus in the fibroadenoma and being quite extensive in the
      remaining two cases. In the phyllodes tumor, PASH areas exhibited focal
      hypercellularity and presence of myoid cells. In none of the cases were there
      cells with intranuclear inclusions or multinucleated cells. The lesions were
      surgically excised. Two patients with follow-up were disease-free at one and
      three years after the operation. As to our knowledge, PASH has not been
      previously described in the anogenital area, this feature seems to have been
      either overlooked or is genuinely rare in this location. It may occur in a
      preexisting lesion of anogenital mammary-like glands or may apparently by itself
      produce a clinically detectable lesion. The clinicopathologic features of PASH in
      the anogenital area seem to be identical to those in the breast.

PMID- 16096416
TI  - Mucinous carcinoid as an unusual manifestation of endodermal differentiation in
      ovarian yolk sac tumors.
AB  - We present, for the first time, two yolk sac tumors (YST) in women 37 and 18
      years of age, one with a typical parietovisceral pattern and the other with a
      glandular pattern, which were associated with extensive areas of mucinous
      carcinoid (MC). The tumor in the first case had numerous nodules of
      tubulopapillary YST that merged with well-differentiated MC. This patient
      responded well to chemotherapy. The tumor in the second case consisted of an AFP
      positive glandular YST, with a glandulopapillary pattern closely resembling fetal
      lung type adenocarcinoma, coexisting with an AFP-negative, cytokeratin 20
      positive, atypical MC; transitional areas between the two components were also
      seen. In the material from the recurrences and metastases; however, no YST was
      present, the atypical MC having become the predominant component including areas
      that had become carcinomatous. There was a poor response to various
      chemotherapeutic regimens. AFP levels became negative during the course of
      disease paralleling the disappearance of the YST component and the overgrowth of
      an increasingly anaplastic MC. The patient died 1 year after diagnosis. We think
      that, in these cases, MC represented an unusual form of endodermal
      differentiation of the YST. It is important to differentiate the yolk sac and
      carcinoid components due to their different responses to chemotherapy and to
      evaluate the possibility of mucinous carcinoid developing into a highly
      aggressive carcinoma.

PMID- 16096417
TI  - Giant multilocular prostate cystoadenoma: an entirely benign prostate neoplasm
      with some phenotypic features of malignancy.

PMID- 16096418
TI  - Aberrant expression of CDX2 in metaplastic and inflammatory epithelium of the
      urinary bladder.

PMID- 16096419
TI  - Does breast massage push tumor cells into sentinel nodes?

PMID- 16096421
TI  - Relationship between pleomorphic hyalinizing angiectatic tumor and nemosiderotic
      fibrohistiocytic lipomatous lesion.

PMID- 16096422
TI  - Lipoblast-like cells in early pleomorphic hyalinizing angiectatic tumor.

PMID- 16096423
TI  - Significance of squamous metaplasia-like change in the esophagus.

PMID- 16096426
TI  - PI3K/Akt/mTOR pathway as a target for cancer therapy.
AB  - The PI3K/Akt/mTOR pathway regulates several normal cellular functions that are
      also critical for tumorigenesis, including cellular proliferation, growth,
      survival and mobility. Components of this pathway are frequently abnormal in a
      variety of tumors, making them an attractive target for anti-cancer therapy.
      Inhibition of mTOR in patients with cancer became more feasible after the
      development of rapamycin analogs with improved pharmacologic properties. The
      promising activity of these agents in early clinical trials has led to the
      development of ongoing phase III trials in renal cell carcinoma and breast
      cancer. Future studies are needed to identify the patients most likely to benefit
      from this form of therapy, and to define its role in combination with
      chemotherapy, hormones and growth factor inhibitors.

PMID- 16096427
TI  - Usnic acid: a non-genotoxic compound with anti-cancer properties.
AB  - The majority of human tumors bear inactive p53 or cellular factors that down
      regulate the expression and activity of the p53 network. Therefore, finding
      therapies that are effective in such tumors is of great interest. Usnic acid, a
      normal component of lichens, showed activity against the wild-type p53 breast
      cancer cell line MCF7 as well as the non-functional p53 breast cancer cell line
      MDA-MB-231 and the lung cancer cell line H1299 (null for p53). In MCF7 cells
      treated with usnic acid, although there was an accumulation of p53 and p21
      proteins, the transcriptional activity of p53 remained unaffected. We also found
      that there was no phosphorylation of p53 at Ser15 after treatment of MCF7 cells
      with usnic acid, suggesting that the oxidative stress and disruption of the
      normal metabolic processes of cells triggered by usnic acid does not involve DNA
      damage. The property of usnic acid as a non-genotoxic anti-cancer agent that
      works in a p53-independent manner makes it a potential candidate for novel cancer
      therapy.

PMID- 16096428
TI  - Combination of trabectedin and irinotecan is highly effective in a human
      rhabdomyosarcoma xenograft.
AB  - Our objective was to evaluate in vitro and in vivo the effect of the combination
      of trabectedin (Yondelis, ET-743) and irinotecan (CPT-11) or its major metabolite
      SN-38 in a human rhabdomyosarcoma cell line. The schedule trabectedin (1 h)
      followed by irinotecan or SN-38 (24 h) and the opposite sequence (irinotecan or
      SN-38 24 h followed by trabectedin 1 h) were analyzed in a rhabdomyosarcoma cell
      line. In vivo studies were conducted with trabectedin and irinotecan at the doses
      of 0.2 and 20 mg/kg, respectively, simultaneously administered with a q4d x 3
      schedule. In vitro studies indicated an overall additive effect [combination
      index (CI) relatively close to 1.0], with the former schedule slightly superior
      to the latter (at the IC50 effect levels: CI=0.89 versus 1.07). Neither
      transcription nor expression of DNA topoisomerase I was affected by trabectedin
      treatment. In vivo the therapeutic results of the combination were certainly more
      impressive: trabectedin and irinotecan combination caused a strong and long
      lasting effect on tumor growth (tumor volume inhibition=89%, log10 cell
      kill=1.6), whereas each drug given as a single agent was only marginally active.
      The discrepancy between the in vitro and in vivo results suggests possible
      mechanisms involving host cells, other than tumor cells. The striking effects of
      the combination observed in vivo could be related to a combination of a direct
      cytotoxic and an anti-inflammatory indirect effect. The very marked and long
      lasting effect of the trabectedin and irinotecan combination in vivo suggests a
      basis for a clinical evaluation in pediatric patients with rhabdomyosarcoma.

PMID- 16096429
TI  - A novel mechanism of action of the fumagillin analog, TNP-470, in the B16F10
      murine melanoma cell line.
AB  - TNP-470, a semisynthetic derivative of fumagillin, is an acknowledged
      angiogenesis inhibitor, presently undergoing clinical trials. It exerts an anti
      proliferative effect directed against endothelial cells. This effect is known to
      be based on cell cycle inhibition effected by the p53/p21 pathway. We observed
      short-term toxicity of TNP-470 in the B16F10 murine melanoma cell line in vitro
      and investigated the mechanism of action. Cell death occurred as soon as 2 h
      after the addition of TNP-470, without typical apoptotic features. The toxic
      effect could be modulated and it depended on the type of culture medium or
      supplementation with anti-oxidants. Addition of N-acetylcysteine protected B16F10
      cells from TNP-470-induced death and inhibited an increase in the generation of
      reactive oxygen species (ROS), which are detected by the 2',7'
      dichlorodihydrofluorescein diacetate probe. We conclude that TNP-470 can induce
      intracellular generation of ROS, which act toxically inside B16F10 cells. One may
      suggest that this novel activity of TNP-470 might be beneficial in some cases,
      but it could also be responsible for some undesirable side-effects. The
      possibility of its modulation gives a prospect for controlling the action of this
      potential drug and probably its derivatives.

PMID- 16096430
TI  - In vitro and in vivo suppression of growth of hepatocellular carcinoma cells by
      novel traditional Chinese medicine-platinum anti-cancer agents.
AB  - Protein phosphatase 2A (PP2A) is a new target for platinum (Pt)-based cancer
      chemotherapeutic agents. A series of novel Pt complexes containing
      demethylcantharidin, a modified component of a traditional Chinese medicine
      (TCM), [Pt(C8H8O5)(NH2R)2] 1-5 have been shown to inhibit PP2A both in its
      purified form and in cell homogenates. In this study, the potential efficacy of
      compounds 1-5 in suppressing the growth of PP2A-highly expressed liver cancer was
      evaluated. The in vitro anti-proliferative activity of compounds 1-5 was
      investigated in human hepatocellular carcinoma (HCC) cell lines using the MTT
      assay. Compounds 1-5 were about 2-20 and 20-200 times more potent than cisplatin
      and carboplatin, respectively, in SK-Hep1 and HepG2 cells. The in vivo anti-tumor
      efficacies of 1-5 were evaluated in a s.c. inoculated SK-Hep1 xenograft model in
      nude mice. Compounds 1-5 demonstrated definite in vivo activity (giving rise to
      an optimal %T/C as low as 14.5%) without inducing undue toxicity, contrasting the
      lack of activity of cisplatin and carboplatin. In a cisplatin-resistant model
      established in vivo in human HCC, compounds 1-5 could still elicit the same level
      of tumor growth suppression as in the control tumors, demonstrating the
      circumvention of cisplatin cross-resistance. An acute toxicity study in ICR mice
      showed that compounds 1-5 are not nephrotoxic at LD10. The high potency of the
      novel TCM-Pt compounds against liver cancer and the minimal toxicity suggest that
      they have significant potential to be developed into useful Pt-based anti-tumor
      drugs.

PMID- 16096431
TI  - Vitamin K analog (compound 5) induces apoptosis in human hepatocellular carcinoma
      independent of the caspase pathway.
AB  - A systemic vitamin K analog, compound 5 (Cpd 5), possesses the ability to inhibit
      cell growth of tumor cells. Therefore, we investigated the effect of Cpd 5 in
      human hepatocellular carcinoma (HCC) cell lines and evaluated its role in
      apoptosis. Human HCC cell lines were cultured and treated with Cpd 5. Apoptosis
      was assessed using DAPI staining and Annexin-V membrane staining. The expression
      of caspases, XIAP and Bcl-xL was also investigated. Cpd 5 decreased cell
      viability in a dose-dependent manner in two HCC cells (HLE and SK-Hep1)
      containing mutant p53, but not in the HepG2 cell line, which contained wild-type
      p53. Cpd 5-treated HLE and SK-Hep1 cells showed typical apoptotic features,
      nuclear condensation and nuclear fragmentation upon DAPI staining. Positive
      membranous staining for Annexin-V was also seen in these cells. Both caspase-8
      and caspase-3 activities were up-regulated slightly. Pro-caspase-8 protein levels
      decreased slightly in both cells. Although the expression of Bcl-xL was not
      influenced by Cpd 5, that of XIAP decreased in HLE cells. However, the pan
      caspase inhibitor, zVAD, could not significantly prevent Cpd 5-induced apoptosis
      and Cpd 5 could not augment TRAIL-induced apoptosis. These results demonstrate
      that Cpd 5 induced apoptosis in human HCC cell lines, mainly independently of
      caspase activities. This may contribute to its highly potent cytotoxicity toward
      HCC cells.

PMID- 16096432
TI  - Combined effects of zoledronic acid and doxorubicin on breast cancer cell
      invasion in vitro.
AB  - The bisphosphonate zoledronic acid and the cytotoxic drug doxorubicin induce
      synergistic levels of apoptosis in breast cancer cells. As zoledronic acid and
      doxorubicin have been shown to reduce cell invasion and migration, we have
      investigated if these drugs also act synergistically on breast cancer invasion in
      vitro. MCF7 cells were treated with 0.05 microM doxorubicin/4 h followed by 1 or
      10 microM zoledronic acid/24 h (or the reverse sequence). To study invasion, MCF7
      cells were either grown on Transwell membranes coated with Matrigel or in a 24
      well plate. Cells were treated sequentially using the above drug combinations,
      prior to starting the invasion assays for 48 h. Cell growth and death were also
      assessed under the same conditions. We found that invasion of MCF7 cells treated
      with zoledronic acid and doxorubicin was significantly reduced when compared with
      control, but the effect was dependent on drug sequence. At 1 microM, zoledronic
      acid significantly reduced invasion only if cells were pre-treated with
      doxorubicin, but cell growth was unaffected. For 10 microM zoledronic acid,
      invasion was reduced when administered before or after the doxorubicin, but this
      dose of zoledronic acid caused a significant reduction in MCF7 growth. Apoptosis
      was not induced by any of the drug doses and combinations. We conclude that pre
      treatment with 0.05 microM doxorubicin followed by 1 microM zoledronic acid
      reduces invasion when cells were grown on Matrigel. For 10 microM zoledronic
      acid, pre- or post-doxorubicin also reduces invasion, but for this combination
      inhibition of cell growth may contribute to the reduction in invasion observed.

PMID- 16096433
TI  - Matrix metalloproteinase inhibitor Ro 28-2653 in combination with estramustine:
      tumor-reducing effects on hormone-sensitive prostate cancer in rats.
AB  - Therapeutic efficacy of the novel matrix metalloproteinase (MMP) inhibitor, Ro 28
      2653 (5-biphenyl-4-yl-5-[4-(-nitro-phenyl)-piperazin-1-yl]-pyrimidine-2,4,6
      trione), has been shown in various models of different tumor entities. The tumor
      growth-reducing effect has been demonstrated in the orthotopic rat prostate
      Dunning model (subline MatLyLu). Based on these results we investigated Ro 28
      2653 in combination with estramustine on the G subline of the Dunning tumor. This
      subline is characterized by a low metastatic ability and androgen sensitivity.
      Efficacy was determined by recording tumor growth in vivo by magnetic resonance
      imaging (MRI). Tumor cells were injected into the prostates of 81 Copenhagen
      rats. MRI was performed at day 100 and at day 126 after tumor cell injection. The
      duration of therapy was 17 days with daily oral application of Ro 28-2653 (100
      mg/kg) and four i.p. injections of estramustine (7.5 mg/kg). Histological
      evaluations were conducted to provide further information about the effects on
      tumor morphology. Orthotopic tumor induction was successful in 100% of the
      animals. Tumor volume calculations with MRI showed a significant difference
      between the control groups, the animals treated with Ro 28-2653, and the animals
      treated with the combination of Ro 28-2653 and estramustine. The new MMP
      inhibitor Ro 28-2653 reduces tumor growth and provides a compatible therapeutic
      alternative for patients with prostate cancer.

PMID- 16096434
TI  - Effect of androgen deprivation therapy in the thyroid function test of patients
      with prostate cancer.
AB  - We have assessed the effect of androgen deprivation therapy (ADT) in the thyroid
      function test in prostate cancer patients. Serum levels of tri-iodothyronine
      (T3), thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH)
      were determined in a cross-sectional study that included 279 patients diagnosed
      with prostate cancer. A subset of 96 patients free of prostate-specific antigen
      relapse after radical prostatectomy became a control group and 183 patients under
      continuous ADT formed the study group. Sixty-four patients out of the study group
      were treated with luteinizing hormone-releasing hormone (LHRH) agonist and 119
      with LHRH agonist plus bicalutamide. The average time of ADT was 42.5 months (3
      218). Results were as follows. Mean T3 level was 122.7 ng/dl (72.6-213.0) in the
      control group and 123.8 ng/dl (64.4-228.2) in patients under ADT, p=0.472. Mean
      T4 level was 7.66 (1.81-4.30) and 7.66 microg/dl (3.60-13.30), respectively,
      p=0.884. Mean TSH level was 1.58 (0.44-11.70) and 1.81 mU/dl (0.15-6.58),
      respectively, p=0.007. Mean FT4 level was 1.24 (0.80-1.90) and 1.18 ng/dl (0.80
      1.90), respectively, p=0.018. No statistically significant differences between
      the T3, T4, TSH and FT4 serum levels were detected according to the modality of
      ADT. The serum level of TSH was higher than 5 mU/l in six patients (2.1%);
      however, all cases had a normal FT4 serum level. This mild hypothyroidism was
      detected in two of the 96 patients of the control group (2.1%) and in four of the
      183 under ADT (2.2%). Our data show that ADT seems to alter the thyroid function
      test. A statistically significant increase in TSH serum level and a decrease in
      FT4 serum level were detected in patients under ADT. However, only a mild
      hypothyroidism was detected in about 2% of the patients with prostate cancer,
      independently of ADT.

PMID- 16096435
TI  - Pathological complete response rates comparing 3 versus 6 cycles of
      epidoxorubicin and docetaxel in the neoadjuvant setting of patients with stage II
      and III breast cancer.
AB  - We conducted a prospective randomized study to compare the results of 3 cycles of
      epidoxorubicin/docetaxel to 6 cycles of epidoxorubicin/docetaxel prior to surgery
      in breast cancer patients with clinical stages II and III. Forty-five patients
      eligible for neoadjuvant chemotherapy were randomly assigned to receive either 3
      (group 1) or 6 (group 2) cycles of epidoxorubicin/docetaxel prior to surgery.
      Chemotherapy consisted of epidoxorubicin 75 mg/m and docetaxel 75 mg/m on day 1
      in 3-week cycles. The primary endpoint was the pathological complete response
      (pCR) rate; secondary endpoints were the rates of breast-conserving surgery and
      the axillary lymph node status in both groups. A pCR occurred in 10% (two of 20)
      in Group 1 and in 36% (nine of 25) in Group 2, which was statistically
      significant (p=0.045). Breast-conserving surgery could be performed in 70% (14 of
      20) in Group 1 and in 76% (19 of 25) in Group 2 (p=0.065). Axillary lymph node
      status was negative in 45% (nine of 20) in Group 1 and 52% (13 of 25) in Group 2
      (p=0.86). We conclude that 6 cycles of pre-operative epidoxorubicin/docetaxel
      versus 3 cycles of pre-operative epidoxorubicin/docetaxel significantly increases
      the pCR rates for breast cancer patients.

PMID- 16096436
TI  - Bendamustine prolongs progression-free survival in metastatic breast cancer
      (MBC): a phase III prospective, randomized, multicenter trial of bendamustine
      hydrochloride, methotrexate and 5-fluorouracil (BMF) versus cyclophosphamide,
      methotrexate and 5-fluorouracil (CMF) as first-line treatment of MBC.
AB  - Two i.v. regimens, bendamustine, methotrexate and 5-fluorouracil (BMF) and
      cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were compared as first
      line therapy in a randomized, open, multicenter phase III trial including 364
      patients with metastatic breast cancer (MBC). Bendamustine is an anti-neoplastic
      agent with alkylating, but also additional, so far unclear, mechanisms of action.
      We wanted to show the superiority of BMF over CMF in terms of time to progression
      (TTP) (primary endpoint), overall response, response duration, toxicity and
      quality of life (QoL). TTP was significantly longer in the BMF group (8.2 versus
      6.7 months for CMF) (p=0.0071). The effect of BMF on TTP was more pronounced in
      the stratum 'prior adjuvant therapy, no visceral metastases' (p=0.034). Overall
      response rates and QoL did not significantly differ between the regimens. BMF
      caused more mucositis and leukopenias. Thus, bendamustine, when replacing
      cyclophosphamide in the CMF combination, can be expected to produce longer
      progression-free survival in first-line treatment of MBC.

PMID- 16096437
TI  - Effect of exemestane on the lipidemic profile of post-menopausal operable breast
      cancer patients following 5-7 years of adjuvant tamoxifen: preliminary results of
      the ATENA substudy.
AB  - Long-term endocrine therapy for breast cancer may have clinical implications as
      drugs that potentially alter the lipid profile may increase the risk of
      developing cardiovascular disease. In this study, a companion subprotocol to the
      ATENA (Adjuvant post-Tamoxifen Exemestane versus Nothing Applied) trial, we
      compared the effect of the steroidal aromatase inactivator exemestane on the
      lipid profile of post-menopausal women with operable breast cancer in the
      adjuvant setting to that of observation alone following deprivation of 5-7 years
      primary treatment with tamoxifen. In this open-label, randomized, parallel group
      study, 340 post-menopausal patients with operable breast cancer who had been
      treated with tamoxifen for 5-7 years were randomized to either 5 additional years
      of exemestane (25 mg/day; n=172) or observation alone (n=168). Assessments of
      total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL)
      and total serum triglycerides (TRG) were performed at baseline, and at 6 and 12
      months. Total TRG levels were significantly reduced compared with baseline for
      the exemestane and the observational arm. Both total cholesterol and LDL levels
      were significantly increased above that of baseline values by 6 months,
      maintained through to 12 months, with no significant difference between the two
      treatment arms. There was no significant alteration observed for HDL over time or
      between the two arms. We conclude that sequential adjuvant treatment with
      exemestane in post-menopausal operable breast cancer patients following cessation
      of 5-7 years of tamoxifen does not appear to significantly alter the lipidemic
      profile for at least 12 months compared with an observational arm.

PMID- 16096438
TI  - In vitro partition of docetaxel and gemcitabine in human volunteer blood: the
      influence of concentration and gender.
AB  - We have performed in vitro incubations of blood from male and female volunteers
      with gemcitabine and docetaxel alone, and in combination, at different
      concentration gradients in order to investigate changes in partition between red
      blood cells (RBCs), total plasma and the free fraction. After extraction and
      sample pre-treatment, a validated high-performance liquid chromatography method
      followed by UV detection was used to determine the concentrations of both drugs
      in the different blood constituents. The partition ratio [the concentration in
      the erythrocytes divided by the concentration in plasma (E/P)] was calculated.
      The partition ratio of docetaxel varied from 0.02 to 1.44 (mean 0.35), reflecting
      its relatively low affinity for RBCs, probably because of its high plasma protein
      binding (more than 98%). For gemcitabine, the partition ratio varied from 1 to 5,
      reflecting a high affinity for RBCs (less than 10% plasma protein bound). The
      partition ratios of both drugs increased significantly with higher whole-blood
      concentrations, favoring uptake in the erythrocytes when plasma protein binding
      is saturated. Combination incubations showed a complex and unexplained
      interaction between gender and the influence of docetaxel on the partition of
      gemcitabine. We conclude that the incorporation of drugs into the RBC pool may be
      important for transportation to tumor tissue and efficacy. In combination, one
      anti-cancer agent can alter the partition ratios of other anti-cancer agents.

PMID- 16096439
TI  - In vitro partition of irinotecan (CPT-11) in human volunteer blood: the influence
      of concentration, gender and smoking.
AB  - We have performed in vitro incubations of blood from male and female volunteers,
      smokers and non-smokers, with irinotecan at a gradient of different
      concentrations in order to investigate changes of partition between red blood
      cells (RBCs), total plasma and the free fraction. Since irinotecan (CPT-11) is
      not metabolized in vitro, there is no data available on its active metabolite SN
      38. After extraction and sample pre-treatment, a validated high-performance
      liquid chromatography method followed by fluorescence detection was used to
      determine the concentration of the drug in the different blood constituents. The
      partition ratio [the concentration in the erythrocytes divided by the
      concentration in plasma (E/P)] was calculated. The partition ratio of CPT-11
      varied from 0.7 to 2.8, reflecting its relatively high affinity for the
      erythrocyte, probably because of its only moderate plasma protein binding (65%).
      The partition ratios increased significantly with higher whole-blood
      concentrations, favoring uptake in the erythrocytes when plasma protein binding
      is saturated. No gender difference was detected, but we found relatively more CPT
      11 in the erythrocytes of non-smokers compared to smokers. The incorporation of
      drugs into the RBC pool may be important for transportation to tumor tissue and
      efficacy. Smoking can have a significant influence on drug partition in the
      blood.

PMID- 16096440
TI  - Leptomeningeal carcinomatosis in relapsed non-seminoma testis: a 1-year complete
      remission with high-dose chemotherapy.
AB  - A 1-year complete remission could be achieved with high-dose systemic
      chemotherapy in a 33-year-old patient with relapsed germ cell tumor presenting
      with leptomeningeal carcinomatosis (LC). Although LC in general has a very poor
      prognosis for patients with chemosensitive malignancies, systemic chemotherapy
      should be considered.

PMID- 16096441
TI  - A randomized, controlled trial of furosemide with or without albumin in
      hypoproteinemic patients with acute lung injury.
AB  - OBJECTIVE: Hypoproteinemia is a common condition in critically ill patients,
      associated with the development of acute lung injury and acute respiratory
      distress syndrome and subsequent worse clinical outcomes. Albumin with furosemide
      benefits lung physiology in hypoproteinemic patients with acute lung injury/acute
      respiratory distress syndrome, but the independent pharmacologic effects of these
      drugs are unknown. DESIGN: Randomized, double-blinded, placebo-controlled
      multicentered trial. SETTING: Eleven medical, surgical, and trauma intensive care
      units including 190 beds within two university hospital systems. PATIENTS: Forty
      mechanically ventilated patients with acute lung injury/acute respiratory
      distress syndrome, whose serum total protein concentrations were <6.0 g/dL were
      included. Patients were excluded for hemodynamic instability or significant renal
      or hepatic failure. INTERVENTIONS: Subjects were equally randomly allocated to
      receive furosemide with albumin or furosemide with placebo for 72 hrs, titrated
      to fluid loss and normalization of serum total protein concentration.
      MEASUREMENTS AND MAIN RESULTS: The primary outcome was change in oxygenation from
      baseline to day 1, with secondary physiologic and clinical outcomes. There were
      no differences in baseline characteristics of the subjects in relation to group
      assignment. Albumin-treated patients had greater increases in oxygenation (mean
      change in Pao2/Fio2: +43 vs. -24 mm Hg at 24 hrs and +49 vs. -13 mm Hg at day 3),
      serum total protein (1.5 vs. 0.5 g/dL at day 3), and net fluid loss (-5480 vs. 
      1490 mL at day 3) throughout the study period (all p < .05). Fluid bolus
      administration to control patients reduced net negative fluid balance; control
      patients more frequently developed hypotension and had fewer shock-free days,
      which translated to differences in organ failure at study end. CONCLUSIONS: The
      addition of albumin to furosemide therapy in hypoproteinemic patients with acute
      lung injury/acute respiratory distress syndrome significantly improves
      oxygenation, with greater net negative fluid balance and better maintenance of
      hemodynamic stability. Additional randomized clinical trials are necessary to
      examine mechanisms and determine the effect on important clinical outcomes, such
      as the duration of mechanical ventilation.

PMID- 16096442
TI  - Low serum level of high-density lipoprotein cholesterol is a poor prognostic
      factor for severe sepsis.
AB  - OBJECTIVE: To assess the initial serum levels of lipids and lipoproteins and
      their correlations with the clinical outcome for patients with severe sepsis. The
      ability of high-density lipoprotein (HDL) to attenuate lipopolysaccharide (LPS)
      induced cytokine production was also examined in vitro. DESIGN: Prospective,
      observational cohort study. SETTING: Medical intensive care unit (ICU) of a
      tertiary-level university hospital. PATIENTS: Sixty-three consecutive patients
      with severe sepsis. INTERVENTIONS: Blood samples were drawn within the first day
      of severe sepsis and the subsequent 14 days. Clinical outcome, including length
      of ICU stay, infection subsequent to hospital stay, and death, were monitored
      prospectively. MEASUREMENTS AND RESULTS: Compared with the survivors, patients
      who died within 30 days had significantly lower levels of HDL cholesterol and
      apolipoprotein A-I during the first 4 days of severe sepsis. On day 1, HDL
      cholesterol levels correlated inversely with interleukin-6 (r = -0.72; p < .01)
      and tumor necrosis factor (TNF)-alpha (r = -0.70; p < .01) concentrations. Not
      only the overall and sepsis-attributable 30-day mortality rates but also the risk
      of prolonged ICU stay (>7 days) and the hospital-acquired infection rate were
      increased among patients with day 1 levels of HDL cholesterol of <20 mg/dL and
      apolipoprotein A-I of <100 mg/dL. Multivariate analysis identified an HDL
      cholesterol level of <20 mg/dL on day 1 (odds ratio, 12.92; 95% confidence
      interval, 2.73-61.29) and Acute Physiology and Chronic Health Evaluation II score
      (odds ratio, 1.15; 95% confidence interval, 1.04-1.26) as independent predictors
      of the overall 30-day mortality rate. In human macrophages, LPS-induced TNF-alpha
      release was attenuated by incremental doses of HDL cholesterol added
      simultaneously (p < .01). However, HDL failed to suppress LPS-induced TNF-alpha
      production when administered after macrophages were exposed to LPS. CONCLUSIONS:
      A low HDL cholesterol level on day 1 of severe sepsis is significantly associated
      with an increase in mortality and adverse clinical outcomes. In cultured
      macrophages, HDL can attenuate LPS-induced TNF-alpha production only if added
      concomitantly with, but not after, LPS exposure.

PMID- 16096443
TI  - The Critical Care Safety Study: The incidence and nature of adverse events and
      serious medical errors in intensive care.
AB  - OBJECTIVE: Critically ill patients require high-intensity care and may be at
      especially high risk of iatrogenic injury because they are severely ill. We
      sought to study the incidence and nature of adverse events and serious errors in
      the critical care setting. DESIGN: We conducted a prospective 1-year
      observational study. Incidents were collected with use of a multifaceted approach
      including direct continuous observation. Two physicians independently assessed
      incident type, severity, and preventability as well as systems-related and
      individual performance failures. SETTING: Academic, tertiary-care urban hospital.
      PATIENTS: Medical intensive care unit and coronary care unit patients.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcomes of
      interest were the incidence and rates of adverse events and serious errors per
      1000 patient-days. A total of 391 patients with 420 unit admissions were studied
      during 1490 patient-days. We found 120 adverse events in 79 patients (20.2%),
      including 66 (55%) nonpreventable and 54 (45%) preventable adverse events as well
      as 223 serious errors. The rates per 1000 patient-days for all adverse events,
      preventable adverse events, and serious errors were 80.5, 36.2, and 149.7,
      respectively. Among adverse events, 13% (16/120) were life-threatening or fatal;
      and among serious errors, 11% (24/223) were potentially life-threatening. Most
      serious medical errors occurred during the ordering or execution of treatments,
      especially medications (61%; 170/277). Performance level failures were most
      commonly slips and lapses (53%; 148/277), rather than rule-based or knowledge
      based mistakes. CONCLUSIONS: Adverse events and serious errors involving
      critically ill patients were common and often potentially life-threatening.
      Although many types of errors were identified, failure to carry out intended
      treatment correctly was the leading category.

PMID- 16096444
TI  - A system factors analysis of "line, tube, and drain" incidents in the intensive
      care unit.
AB  - OBJECTIVE: To analyze the system factors related to "line, tube, and drain" (LTD)
      incidents in the intensive care unit (ICU). DESIGN: Voluntary, anonymous Web
      based patient safety reporting system. SETTING: Eighteen ICUs in the United
      States. PATIENTS: Incidents reported by ICU staff members during a 12-month
      period ending June 2003. INTERVENTIONS: None. MEASUREMENTS: Characteristics of
      the incidents (defined as events that could/did cause harm), patients, and
      patient harm were described. Separate multivariable logistic regression analyses
      of contributing, limiting, and preventive system factors for LTD vs. non-LTD
      incidents were reported. MAIN RESULTS: Of the 114 reported LTD incidents, >60%
      were considered preventable. One patient death was attributed to an LTD incident.
      Of patients experiencing LTD incidents, 56% sustained physical injury, and 23%
      had an anticipated increased hospital stay. Factors contributing to LTD incidents
      included occurrence in the operating room (odds ratio [OR], 3.50; 95% confidence
      interval [CI], 1.25-9.83), occurrence on a holiday (OR, 3.65; 95% CI, 1.12-11.9),
      patient medical complexity (OR, 3.68; 95% CI, 2.28-5.92), and age of 1-9 yrs (OR,
      7.95; 95% CI, 3.29-19.2). Factors related to team communication were less likely
      to limit LTD incidents (OR, 0.28; 95% CI, 0.11-0.68), while clinician knowledge
      and skills helped prevent LTD incidents (OR, 1.80; 95% CI, 1.09-2.97).
      CONCLUSIONS: Patients are harmed by preventable LTD incidents. Relative to non
      LTD events, these incidents occur more frequently during holidays and in
      medically complex patients and children. Focusing on these contributing factors
      and clinician knowledge and skills is important for reducing and preventing these
      hazardous events.

PMID- 16096445
TI  - Outcome measures for clinical research in sepsis: a report of the 2nd Cambridge
      Colloquium of the International Sepsis Forum.
AB  - BACKGROUND AND OBJECTIVES: Sepsis is the leading cause of morbidity and mortality
      for patients admitted to an intensive care unit. The evaluation of new therapies
      has been hampered by the underdevelopment of outcome measures used to detect
      biological activity and patient-centered benefit in a complex and highly
      heterogeneous patient population. We sought to evaluate existing approaches and
      to draw on insights from other disciplines to propose a comprehensive approach to
      outcome evaluation in sepsis clinical trials. METHODS: An expert colloquium
      organized by the International Sepsis Forum brought together sepsis researchers,
      clinical epidemiologists, and experts in the development and implementation of
      outcome measures in rheumatology, neurology, and oncology. RESULTS: The
      translation of an evolving understanding of the biology of sepsis into effective
      new therapies for critically ill patients requires a reevaluation of the end
      points used to determine response to intervention. These represent a continuum
      that measures biological activity against the target at one end and sustained
      improvement in survival or quality of life at the other. Early phase research
      should determine whether an intervention works in vivo, using measures that are
      responsive and informative to provide proof of principle, to aid in selecting
      optimal patient populations for study, and to gain insights into optimal dose and
      duration of therapy. After in vivo biology has been demonstrated and the
      possibility of efficacy inferred by plausible improvements in surrogate
      physiologic measures, definitive studies should seek robust evidence of benefit
      using end points that measure important, patient-centered benefit, including
      intermediate and longer term survival and health-related quality of life.
      Nonmortal measures of benefit assume particular importance for populations, such
      as children, whose mortality risk is low, or who have significant rates of
      comorbidities that independently limit survival. Composite measures that
      integrate morbidity and mortality effects may provide the most meaningful
      information about therapeutic efficacy. CONCLUSIONS: The development of explicit,
      hypothesis-driven, and iterative approaches to outcome measure development,
      patterned on approaches used in the fields of rheumatology and oncology, may
      improve the conduct of clinical studies in the critically ill.

PMID- 16096447
TI  - Procedural experience with out-of-hospital endotracheal intubation.
AB  - OBJECTIVE: Out-of-hospital rescuers likely need regular clinical experience to
      perform endotracheal intubation (ETI) in a safe and effective manner. We sought
      to determine the frequency of ETI performed by individual out-of-hospital
      rescuers. DESIGN: Analysis of an administrative database of all emergency medical
      services (EMS) patient care reports in Pennsylvania. SETTING: Commonwealth of
      Pennsylvania from January 1 to December 31, 2003. SUBJECTS: EMS advanced life
      support rescuers (paramedics, prehospital nurses, and EMS physicians) who
      reported at least one patient contact during the study period. INTERVENTIONS:
      None. MEASUREMENTS: We calculated individual rescuer ETI frequency and
      opportunity. We evaluated relationships between ETI frequency and the number of
      patient contacts. We also examined the relationship with practice setting (air
      medical vs. ground rescuers and urban vs. rural rescuers). MAIN RESULTS: In
      1,544,791 patient care reports, 11,484 ETIs were reported by 5,245 out-of
      hospital rescuers. The median ETI frequency was one (interquartile range, 0-3;
      range, 0-23). Of 5,245 rescuers, >67% (3,551) performed two or fewer ETIs, and
      >39% (2,054) rescuers did not perform any ETIs. The median number of ETI
      opportunities was three (interquartile range, 0-6; range, 0-76). ETI frequency
      was associated with patient volume (Spearman's rho = 0.67) and was higher for air
      medical (p = .006) and urban (p < .0001) rescuers. ETI frequency was not
      associated with response (Spearman's rho = -0.01) or transport (Spearman's rho = 
      0.06) times. CONCLUSIONS: Out-of-hospital ETI, an important and difficult
      resuscitation intervention, is an uncommon event for most rescuers.

PMID- 16096448
TI  - Intragastric nitric oxide is abolished in intubated patients and restored by
      nitrite.
AB  - OBJECTIVE: Nitrite in saliva is reduced to nitric oxide (NO) in the acidic
      stomach, and this NO may serve gastroprotective functions. We studied
      intragastric NO levels in healthy controls and in intubated intensive care unit
      patients before and after supplementation with nitrite. DESIGN: Prospective
      observational study involving patients and controls. SETTING: A mixed intensive
      care unit and a university laboratory. PATIENTS AND SUBJECTS: Eight healthy
      volunteers and ten intubated, mechanically ventilated intensive care unit
      patients. INTERVENTIONS: A tonometric catheter was first evaluated in vitro and
      then used for all NO measurements. In fasting controls, gastric NO levels were
      measured repeatedly during periods of saliva depletion and after an intragastric
      nitrite infusion. In patients, changes in levels of intragastric NO, nitrite in
      plasma and gastric juice, and S-nitrosothiols in gastric juice were measured in
      response to an intragastric nitrite infusion. MEASUREMENTS AND MAIN RESULTS: The
      tonometric catheter had a recovery of 80% with a high intraclass and interclass
      correlation. Median baseline NO levels in healthy volunteers were 21.6 ppm
      (interquartile range, 11.4-22.3 ppm) and decreased by 90% to 3.3 ppm (2.0-5.2
      ppm) during 25-50 mins of saliva depletion. The NO level was restored by an
      intragastric nitrite infusion. Baseline NO levels in patients were almost
      abolished (0.1 ppm [0.07-0.4 ppm]) but increased rapidly to 124 ppm (range, 65
      180 ppm) during intragastric nitrite infusion. Nitrite levels in plasma increased
      from 0.18 +/- 0.03 to 1.3 +/- 0.2 microM (p < .01), and levels of S-nitrosothiols
      in gastric juice increased from 0.12 +/- 0.09 to 6.7 +/- 1.8 microM. CONCLUSIONS:
      Intragastric generation of NO requires continuous delivery of nitrite-containing
      saliva and is almost abolished in critically ill, intubated patients. Enteral
      supplementation with nitrite could however fully restore gastric NO levels.
      Future studies will reveal if low NO levels contribute to stress ulcers and
      gastric overgrowth of bacteria often seen in these patients and in turn if
      restoring gastric NO with nitrite could be a useful therapeutic approach.

PMID- 16096449
TI  - Effect of gingival and dental plaque antiseptic decontamination on nosocomial
      infections acquired in the intensive care unit: a double-blind placebo-controlled
      multicenter study.
AB  - OBJECTIVE: To document the effect of gingival and dental plaque antiseptic
      decontamination on the rate of nosocomial bacteremias and respiratory infections
      acquired in the intensive care unit (ICU). DESIGN: Prospective, multicenter,
      double-blind, placebo-controlled efficacy study. SETTING: Six ICUs: three in
      university hospitals and three in general hospitals. PATIENTS: A total of 228
      nonedentulous patients requiring endotracheal intubation and mechanical
      ventilation, with an anticipated length of stay > or =5 days. INTERVENTIONS:
      Antiseptic decontamination of gingival and dental plaque with a 0.2%
      chlorhexidine gel or a placebo gel, three times a day, during the entire ICU
      stay. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical characteristics,
      organ function data (Logistic Organ Dysfunction score), severity of condition
      (Simplified Acute Physiologic Score), and dental plaque status were assessed at
      baseline and until 28 days. Bacteriologic sampling of dental plaque and saliva
      was done every 5 days, and blood, tracheal aspirate, and bronchoalveolar lavage
      cultures were performed when appropriate. The primary efficacy end point was the
      incidence of bacteremia, bronchitis, and ventilator-associated pneumonia,
      expressed as a percentage and per 1000 ICU days. All baseline characteristics
      were similar between the treated and the placebo groups. The incidence of
      nosocomial infections was 17.5% (13.2 per 1000 ICU days) in the placebo group and
      18.4% (13.3 per 1000 ICU days) in the plaque antiseptic decontamination group
      (not significant). No difference was observed in the incidence of ventilator
      associated pneumonia per ventilator or intubation days, mortality, length of
      stay, and care loads (secondary end points). On day 10, the number of positive
      dental plaque cultures was significantly lower in the treated group (29% vs. 66%;
      p < .05). Highly resistant Pseudomonas, Acinetobacter, and Enterobacter species
      identified in late-onset ventilator-associated pneumonia and previously cultured
      from dental plaque were not eradicated by the antiseptic decontamination. No side
      effect was reported. CONCLUSIONS: Gingival and dental plaque antiseptic
      decontamination significantly decreased the oropharyngeal colonization by aerobic
      pathogens in ventilated patients. However, its efficacy was insufficient to
      reduce the incidence of respiratory infections due to multiresistant bacteria.

PMID- 16096450
TI  - Somatosensory and brainstem auditory evoked potentials in cardiac arrest patients
      treated with hypothermia.
AB  - OBJECTIVE: To evaluate the prognostic value of short-latency median nerve
      somatosensory evoked potentials and brainstem auditory evoked potentials in
      outcome prediction for comatose cardiac arrest patients treated with hypothermia.
      DESIGN: Prospective, randomized, controlled trial of mild hypothermia after out
      of-hospital cardiac arrest; a substudy of the European Hypothermia After Cardiac
      Arrest study. SETTING: Intensive care unit of a tertiary referral hospital
      (Helsinki University Central Hospital). PATIENTS: Sixty consecutive patients
      (aged 18-75 yrs) resuscitated from out-of-hospital ventricular fibrillation and
      comatose at 24 hrs after cardiac arrest; all patients were randomly assigned
      either to therapeutic hypothermia of 33 degrees C or normothermia. INTERVENTIONS:
      All patients received standard intensive care for at least 2 days. Patients
      randomized to hypothermia were cooled with an external cooling device for 24 hrs
      and then allowed to rewarm slowly for 12 hrs. In the normothermia group, the core
      temperature was kept below 38 degrees C with antipyretics and by physical means.
      The clinical outcome was assessed 6 months after cardiac arrest. MEASUREMENTS AND
      MAIN RESULTS: Somatosensory evoked potentials and brainstem auditory evoked
      potentials were recorded 24-28 hrs after cardiac arrest. All wave latencies were
      significantly prolonged in the hypothermia group. Bilaterally absent N20 waves
      predicted permanent coma with a specificity of 100% in both treatment groups.
      Brainstem auditory evoked potential recordings did not correlate with the outcome
      in either treatment group. CONCLUSIONS: The prognostic ability of median nerve
      short-latency somatosensory evoked potentials does not seem to be affected by
      therapeutic hypothermia. Brainstem auditory evoked potentials had no additional
      value in outcome prediction.

PMID- 16096451
TI  - LY315920NA/S-5920, a selective inhibitor of group IIA secretory phospholipase A2,
      fails to improve clinical outcome for patients with severe sepsis.
AB  - OBJECTIVE: Group IIA secretory phospholipase A2 (sPLA2-IIA), released during
      inflammation, is increased in severe sepsis, and plasma levels are inversely
      related to survival. In a previous study, a selective inhibitor of sPLA2-IIA
      (LY315920NA/S-5920) was well tolerated and appeared to improve survival in a
      subgroup of patients who received the drug within 24 hrs of first sepsis-induced
      organ failure. This study was designed to determine whether improvement in
      survival could be confirmed in a larger patient population meeting the
      characteristics of that subgroup. DESIGN: Multicenter, double-blind, placebo
      controlled, parallel-group clinical trial of LY315920NA/S-5920 in patients with
      severe sepsis. SETTING: Seventy-five institutions worldwide. PATIENTS: A total of
      373 patients with at least two sepsis-induced organ failures. INTERVENTIONS:
      Patients were randomized 1:1 to receive LY315920NA/S-5920 (target plasma
      concentration of 800 ng/mL; n = 188) or placebo (n = 185). Study medication was
      administered as a continuous intravenous infusion for 168 hrs. MEASUREMENTS AND
      MAIN RESULTS: The study was terminated after data on 250 patients suggested a
      significant improvement in 28-day all-cause mortality would not be found if the
      trial continued as planned. The mortality rate was 39.4% in the LY315920NA/S-5920
      group, compared with 31.9% in the placebo group (p = .092). The negative trend in
      mortality was most pronounced among patients with cardiovascular failure at
      baseline (41.6% vs. 28.7%; p = .008) and patients whose culture data at baseline
      were negative (42.9% vs. 22.7%; p = .045). The negative trend in mortality is not
      explained by adverse events, microbiology, or laboratory data. CONCLUSIONS:
      Continuous 7-day infusion of an inhibitor of sPLA2-IIA had no beneficial effect
      on 28-day all-cause mortality among severe sepsis patients with at least two
      organ failures. This study did not confirm earlier promising subgroup results
      with LY315920NA/S-5920, which provides a reminder that subgroup effects should be
      viewed cautiously, especially when primary effects are not significant.

PMID- 16096452
TI  - Role of hemodilutional anemia and transfusion during cardiopulmonary bypass in
      renal injury after coronary revascularization: implications on operative outcome.
AB  - OBJECTIVE: Acute renal injury and failure (ARF) after cardiopulmonary bypass
      (CPB) has been linked to low on-pump hematocrit (hematocrit). We aimed to 1)
      elucidate if and how this relation is modulated by the duration of CPB (TCPB) and
      on-pump packed red blood cell transfusions and 2) to quantify the impact of post
      CPB renal injury on operational outcome and resource utilization. DESIGN:
      Retrospective review. SETTING: A Northwest Ohio community hospital. PATIENTS:
      Adult coronary artery bypass surgery patients with CPB but no preoperative renal
      failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We quantified post
      CPB renal injury via 1) the peak postoperative change in serum creatinine (Cr)
      level relative to pre-CPB values (%DeltaCr) and 2) ARF, defined as the
      coincidence of post-CPB Cr > or =2.1 mg/dL and >2 times pre-CPB Cr. The separate
      effects of lowest hematocrit, intraoperative packed RBC transfusions, and TCPB on
      %DeltaCr and ARF were derived via multivariate regression, overlapping quintile
      subgroup analyses, and propensity matching. Lowest hematocrit (22.0% +/- 4.6%
      sd), TCPB (94 +/- 35 mins), and pre-CPB Cr (1.01 +/- 0.23 mg/dL) varied widely.
      %DeltaCr varied substantially (24 +/- 57%), and ARF was documented in 89 patients
      (5.1%). Both %DeltaCr (p < .001) and ARF (p < .001) exhibited sigmoidal dose
      dependent associations to lowest hematocrit that were 1) modulated by TCPB such
      that the renal injury was exacerbated as TCPB increased, 2) worse in patients
      with relatively elevated pre-CPB Cr (> or =1.2 mg/dL), and 3) worse with
      intraoperative packed red blood cell transfusions (n = 385; 21.9%), in comparison
      with patients at similar lowest hematocrit. Operative mortality (p < .01) and
      hospital stays (p < .001) were increased systematically and significantly as a
      function of increased post-CPB renal injury. CONCLUSIONS: CPB hemodilution to
      hematocrit <24% is associated with a systematically increased likelihood of renal
      injury (including ARF) and consequently worse operative outcomes. This effect is
      exacerbated when CPB is prolonged with intraoperative packed red blood cell
      transfusions and in patients with borderline renal function. Our data add to the
      concerns regarding the safety of currently accepted CPB practice guidelines.

PMID- 16096453
TI  - Quantitative assessment of pleural effusion in critically ill patients by means
      of ultrasonography.
AB  - OBJECTIVE: To assess the ability of ultrasonography to identify the presence and
      assess the volume of pleural effusion in the intensive care unit setting. DESIGN:
      Prospective descriptive clinical study. SETTING: Medical-surgical intensive care
      unit of a teaching hospital. PATIENTS: Initial study group (group I) consisted of
      97 patients (mean [+/-SD] Simplified Acute Physiology Score II, 40 +/- 14) with
      clinically suspected pleural effusion. Fifty-one patients were mechanically
      ventilated and 55 patients underwent a unilateral or bilateral thoracentesis (58
      procedures). All patients underwent supine chest radiography and pleural
      ultrasonography at bedside. The testing group (group II) consisted of 19
      additional patients (17 under ventilation) who underwent thoracentesis.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Maximal interpleural distance
      was measured at the base and apex of the pleural space, at both end-expiration
      and end-inspiration. In group I, interpleural distances were compared to actual
      volume of fluid in the subset of patients who underwent a complete thoracentesis
      (n = 49). Prediction of the volume of pleural effusion was subsequently tested
      prospectively in group II (25 complete thoracenteses). Portable chest radiography
      and pleural ultrasonography yielded discordant results for 47 patients (48%) in
      the diagnosis of pleural effusion. The expiratory interpleural distance measured
      at the thoracic base with ultrasonography was significantly correlated with the
      volume of fluid (p < .0001; coefficient of determination: right, 0.78; left,
      0.51). A pleural effusion > or =800 mL was predicted when this distance was >45
      mm (right) or >50 mm (left), with a sensitivity of 94% and 100% and a specificity
      of 76% and 67%, respectively. In group II, the mean bias between the predicted
      and observed volumes of pleural effusion determined by thoracentesis was 24 +/-
      355 mL, and this decreased to 28 +/- 146 mL for the prediction of pleural
      effusion <1400 mL. CONCLUSIONS: Bedside ultrasonography is well suited for the
      quantitative assessment of unloculated pleural effusions in intensive care unit
      patients.

PMID- 16096454
TI  - Randomized, controlled clinical trial of point-of-care limited ultrasonography
      assistance of central venous cannulation: the Third Sonography Outcomes
      Assessment Program (SOAP-3) Trial.
AB  - CONTEXT: A 2001 Agency for Healthcare Research and Quality Evidence Report on
      patient safety addressed point-of-care limited ultrasonography guidance for
      central venous cannulation and strongly recommended real-time, dynamic guidance
      for all central cannulas. However, on the basis of one limited study, the report
      dismissed static assistance, a "quick look" with ultrasound to confirm vein
      location before preparing the sterile field, as unhelpful. OBJECTIVE: The
      objective of this trial was to compare the overall success rate of central
      cannula placement with use of dynamic ultrasound (D), static ultrasound (S), and
      anatomical landmarks (LM). DESIGN AND SETTING: A concealed, randomized,
      controlled, clinical trial conducted from September 2003 to February 2004 in a
      U.S. urban teaching hospital. PATIENTS: Two-hundred one patients undergoing
      internal jugular vein central venous cannulation. INTERVENTIONS: Patients were
      randomly assigned to three groups: 60 to D, 72 to S, and 69 to LM. An iLook25
      SonoSite was used for all imaging. MEASUREMENTS AND MAIN RESULTS: Cannulation
      success, first-attempt success, and number of attempts were noted. Other measures
      were vein size and clarity of LM. Results, controlled for pretest difficulty
      assessment, are stated as odds improvement (95% confidence interval) over LM for
      D and S. D had an odds 53.5 (6.6-440) times higher for success than LM. S had an
      odds 3 (1.3-7) times higher for success than LM. The unadjusted success rates
      were 98%, 82%, and 64% for D, S, and LM. For first-attempt success, D had an odds
      5.8 (2.7-13) times higher for first success than LM, and S had an odds 3.4 (1.6
      7.2) times higher for first success than LM. The unadjusted first-attempt success
      rates were 62%, 50%, and 23% for D, S, and LM. CONCLUSIONS: Ultrasound assistance
      was superior to LM techniques. D outperformed S but may require more training and
      personnel. All central cannula placement should be conducted with ultrasound
      assistance. The 2001 Agency for Healthcare Research and Quality Evidence Report
      dismissing static assistance was incorrect.

PMID- 16096455
TI  - Aspiration pneumonitis primes the host for an exaggerated inflammatory response
      during pneumonia.
AB  - OBJECTIVE: Nosocomial pneumonia is a feared complication in the critically ill
      patient. Aspiration pneumonitis is frequently complicated by infections. The
      objective of this study was to determine the influence of aspiration pneumonitis
      on the host response to a common nosocomial respiratory pathogen. DESIGN:
      Controlled, in vivo laboratory study. SETTING: Research laboratory of a health
      sciences university. SUBJECTS: Female C57Bl/6 mice. INTERVENTIONS: Mice received
      hydrochloric acid or saline intratracheally followed 16 hrs later by Klebsiella
      pneumoniae. MEASUREMENTS AND MAIN RESULTS: Hydrochloric acid induced a mild
      aspiration pneumonitis. Nonetheless, hydrochloric acid aspiration resulted in a
      markedly increased inflammatory response in the lung on infection with K.
      pneumoniae. This enhanced inflammatory reaction was accompanied by a greatly
      increased outgrowth of K. pneumoniae in lungs of mice previously exposed to
      hydrochloric acid. Preexisting aspiration pneumonitis also triggered mouse lungs
      in vivo and alveolar macrophages ex vivo for enhanced release of proinflammatory
      mediators on stimulation with Klebsiella lipopolysaccharide. Inhibition of tumor
      necrosis factor-alpha resulted in an increased inflammatory reaction and enhanced
      bacterial outgrowth in mice with primary K. pneumoniae pneumonia, whereas it had
      no effect in mice with preexisting aspiration pneumonitis. CONCLUSIONS: These
      data indicate a) that aspiration pneumonitis renders the host more susceptible to
      respiratory tract infection with K. pneumoniae, concurrently priming the lung for
      an exaggerated inflammatory response; and b) that although tumor necrosis factor
      alpha plays a major role in the host response to primary infection, it does not
      affect lung inflammation or defense after aspiration pneumonitis.

PMID- 16096456
TI  - Dehydroepiandrosterone restores depressed peripheral blood mononuclear cell
      function following major abdominal surgery via the estrogen receptors.
AB  - OBJECTIVE: Peripheral blood mononuclear cell (PBMC) dysfunction occurs following
      major abdominal surgery and correlates with an increased rate of septic
      complications. Studies have shown that dehydroepiandrosterone (DHEA) restores
      cell-mediated immune responses after trauma-hemorrhage in mice. Nonetheless, it
      remains unknown whether DHEA has any salutary effects on depressed PBMC function
      in surgical patients. DESIGN: Laboratory experiment. SETTING: University
      laboratory. PATIENTS: Fifteen patients undergoing major abdominal surgery.
      INTERVENTIONS: Blood samples were obtained preoperatively and 2 hrs
      postoperatively. MEASUREMENTS AND MAIN RESULTS: PBMCs were cultured with 33%
      plasma in the presence or absence of DHEA (10(-10) M, 10(-8) M physiologic
      concentration, 10(-6) M, 10(-5) M). In an additional set of samples, the estrogen
      receptor antagonist tamoxifen (10(-6) M) was added. The release of
      proinflammatory cytokines (interleukin-1beta, interleukin-6, and tumor necrosis
      factor-alpha) was measured in the supernatants by enzyme-linked immunosorbent
      assay. Abdominal surgery resulted in depressed interleukin-1beta and tumor
      necrosis factor-alpha release by PBMC. Addition of DHEA to the culture medium,
      however, significantly improved the release of interleukin-1beta and tumor
      necrosis factor-alpha and stimulated the interleukin-6 release capacity of PBMC.
      This effect was most pronounced for a concentration of 10(-5)M DHEA. The
      immunomodulatory effect of DHEA on PBMC cytokine release was completely blocked
      by tamoxifen. In contrast, the modulatory effect of DHEA was enhanced by the
      addition of postoperative plasma. CONCLUSIONS: DHEA stimulates proinflammatory
      cytokine release capacities of human PBMCs following major abdominal surgery. The
      estrogen receptor appears to be involved in mediating the immunomodulatory effect
      of DHEA. Thus, DHEA might be a useful adjunct for preventing immunosuppression in
      surgical patients.

PMID- 16096457
TI  - Surface and soluble triggering receptor expressed on myeloid cells-1: expression
      patterns in murine sepsis.
AB  - OBJECTIVE: To examine the expression patterns of the triggering receptor
      expressed on myeloid cells (TREM)-1 during experimental septic shock. DESIGN:
      Animal study. SETTING: Animal research laboratory. SUBJECTS: Male BALB/c mice, 7
      9 wks of age. INTERVENTIONS: Septic shock was induced by cecal ligation and
      puncture in eight mice. Eight additional animals were sham-operated and served as
      a control group. All animals were resuscitated by fluid infusion and administered
      antibiotics. Kill was performed under anesthesia 12, 24, or 48 hrs later.
      MEASUREMENTS AND MAIN RESULTS: Surface expression of TREM-1 was analyzed using
      flow cytometry on peripheral blood cells, peritoneal macrophages and neutrophils,
      splenic macrophages, and Kupffer cells. Gene expression was also studied in these
      same cells using reverse transcription-polymerase chain reaction. Tumor necrosis
      factor-alpha, interleukin-1beta, and soluble TREM-1 concentrations were
      determined in plasma and peritoneal lavage fluid. Sepsis strongly induced TREM-1
      gene expression, which translated into an up-regulation of TREM-1 surface
      expression on neutrophils and monocytes/macrophages both at the focus on
      infection as well as distally. Moreover, sepsis induced the release of
      significant levels of soluble TREM-1. Plasma soluble TREM-1 concentrations
      negatively correlated with tumor necrosis factor-alpha and interleukin-1beta
      levels at 12 hrs. CONCLUSIONS: These results provide new information as to the
      regulation of TREM-1 during sepsis. Considering that both cell-surface and
      soluble TREM-1 were strongly up-regulated during infection, this study may add
      support to the putative usefulness of TREM-1 as a diagnostic tool.

PMID- 16096458
TI  - MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival
      after uncontrolled hemorrhage in anesthetized swine.
AB  - OBJECTIVES: MalPEG-hemoglobin, 4 g/dL (MP4), is a hemoglobin-based oxygen carrier
      with a low hemoglobin concentration, low P50 (oxygen half-saturation pressure of
      hemoglobin), high colloid osmotic pressure, and high viscosity. This study
      evaluated resuscitation with MP4 in anesthetized swine hemorrhaged 250 mL by
      controlled withdrawal, followed by a 5-mm tear in the abdominal aorta. DESIGN:
      Randomized, unblinded. SETTING: Academic animal laboratory. SUBJECTS:
      Anesthetized male and female Swedish Landrace pigs. INTERVENTIONS: Four groups of
      pigs (n = 7 each) were randomized after hemorrhage by aortic tear to receive 250
      mL of MP4, Ringer's acetate, 10% pentastarch, or 4 g/dL of stroma-free
      hemoglobin, followed by aortic repair and transfusion of 250 mL of autologous
      blood. End points were 20-hr survival, hemodynamic variables, and acid-base
      status. MEASUREMENTS AND MAIN RESULTS: Measurements included continuous aortic,
      pulmonary arterial, and central venous pressures, cardiac output by
      thermodilution, arterial and venous blood gases; electrolytes; lactate; base
      excess; oxygen delivery, consumption, and extraction ratio; hematocrit;
      hemoglobin; and urine output. Body weight (24-27 kg) and hemorrhage volume (26-33
      mL/kg) were similar in the four groups. The nadir of mean arterial pressure (22
      28 mm Hg) and the increase in lactic acid (5-8 mEq/L) after hemorrhage were
      similar in all groups, indicating equivalent shock in the four groups. Survival
      was greatest in the MP4-treated animals (six of seven) compared with Ringer's
      acetate (two of seven), 10% pentastarch (one of seven), and stroma-free
      hemoglobin (two of seven) and was accompanied by an improved recovery of arterial
      pressure, cardiac output, and lactate. Total hemoglobin concentration was
      equivalent in all groups. Arterial pressure did not increase above baseline
      values, and systemic vascular resistance was unchanged following administration
      of MP4, indicating the lack of peripheral vasoconstriction. Mortality in Ringer's
      acetate, stroma-free hemoglobin, and 10% pentastarch treated animals was
      associated with deteriorating acid-base status, low urine output, and
      hyperkalemia. CONCLUSION: These data demonstrate that restoration of oxygen
      delivery with a small volume of MP4 yields significant recovery from hemorrhage
      without systemic vasoconstriction.

PMID- 16096459
TI  - Effect of systemic hypothermia on local soft tissue trauma-induced
      microcirculatory and cellular dysfunction in mice.
AB  - OBJECTIVE: Changes in body temperature occur as a systemic reaction to severe
      trauma; however, its role in the manifestation of injury remains unclear.
      Thermoregulatory responses vary considerably from fever to hypothermia. Although
      hypothermic trauma patients seem to have a worse prognosis, there is the question
      whether hypothermia per se or the severity of trauma producing the hypothermia is
      responsible for aggravated injury and increased mortality rate. The present study
      unravels how moderate to severe systemic hypothermia modulates local
      microcirculatory dysfunction and cellular injury in local soft tissue trauma.
      DESIGN: Prospective, experimental study. SETTING: Research laboratory at a
      university. SUBJECTS: C57BL/6J mice. INTERVENTIONS: A model involving
      standardized drop weight device-induced tissue trauma and high-resolution
      multifluorescence microscopy in the dorsal skinfold chamber was used to show
      arteriolar vasoconstriction, reduction of blood flow, nutritive perfusion
      failure, and apoptotic cell death at 1 hr after trauma. MEASUREMENTS AND MAIN
      RESULTS: During the 8-hr posttrauma observation period, microcirculation, but not
      apoptosis, restituted to almost baseline level. Concomitant systemic hypothermia
      of either 34 degrees C or 30 degrees C did not affect late manifestation of
      apoptotic cell death but aggravated initial microcirculatory dysfunction and
      inhibited recovery during the 8-hr follow-up period. CONCLUSIONS: Our study
      provides evidence that systemic hypothermia may aggravate soft tissue trauma
      associated microcirculatory dysfunction. These experimental results clearly
      support clinical efforts to prevent hypothermia in the acutely traumatized
      patient.

PMID- 16096460
TI  - Protective effects of a selective neutrophil elastase inhibitor (sivelestat) on
      lipopolysaccharide-induced acute dysfunction of the pulmonary microcirculation.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of a neutrophil
      elastase inhibitor, sivelestat, on lipopolysaccharide-induced acute lung injury
      through analysis of hemodynamic changes in the pulmonary microcirculation.
      DESIGN: Randomized animal study. SETTING: Medical school laboratory. SUBJECTS:
      Twenty-seven Wistar rats (15 rats for microspectroscopic observations, 12 rats
      for measurements of neutrophil elastase activity and wet-to-dry ratio).
      INTERVENTIONS: Thoracosternotomy was performed on male Wistar rats under
      continuous anesthesia and mechanical ventilation. Rats were divided into three
      groups (n = 5 each groups) on the basis of the reagent used: lipopolysaccharide
      group (100 microg/kg lipopolysaccharide intravenously), sivelestat group (10
      mg/kg sivelestat; 100 microg/kg lipopolysaccharide intravenously), and control
      group (saline only, intravenously). MEASUREMENTS AND MAIN RESULTS: We measured
      morphologic changes and hemodynamic variables, including tissue blood flow,
      erythrocyte velocity, erythrocyte count, thickness of interalveolar septa, and
      leukocyte adhesion in the pulmonary microcirculation, with a video-rate (33
      msec/frame) dual-spot microspectroscopy system (DSMSS) and a laser-Doppler
      flowmeter. Blood-free wet-to-dry ratio and neutrophil elastase activity in
      bronchoalveolar lavage fluid, serum, and supernatant of lung homogenate were
      measured in another set of experiments (n = 4 for each group). Sixty minutes
      after lipopolysaccharide administration, severe thickening of the interalveolar
      septa was observed in the lipopolysaccharide but not the sivelestat group. In the
      lipopolysaccharide group, DSMSS measurements of erythrocyte velocity and
      hemoglobin oxygenation in single capillaries were decreased significantly (vs.
      control p < .05, vs. sivelestat p < .01), whereas tissue blood flow and
      erythrocyte velocity measurements from laser-Doppler flowmeter were increased
      significantly (vs. control p < .05, vs. sivelestat p < .01). The number of
      adherent leukocytes was increased significantly in the lipopolysaccharide group
      at 30, 45, and 60 mins after lipopolysaccharide administration (vs. control p <
      .01, vs. sivelestat p < .05). The number of adherent leukocytes did not increase
      in the sivelestat group. The wet-to-dry ratio was significantly higher in the
      lipopolysaccharide group than in control (p < .05) and sivelestat (p < .05)
      groups. Neutrophil elastase activities in the bronchoalveolar lavage fluid,
      serum, and lung tissue were all significantly lower in the sivelestat group than
      in the lipopolysaccharide group (p < .05). CONCLUSIONS: Lipopolysaccharide
      induces leukocyte adhesion in the pulmonary microcirculation, resulting in
      decreased tissue hemoglobin oxygen and alveolar and interstitial edema. The
      selective neutrophil elastase inhibitor sivelestat reduces neutrophil elastase
      activity and attenuates acute changes in the pulmonary microcirculation.

PMID- 16096461
TI  - Delayed ascorbate bolus protects against maldistribution of microvascular blood
      flow in septic rat skeletal muscle.
AB  - OBJECTIVE: Although early administration of ascorbate has been shown to protect
      against the microvascular dysfunction in sepsis, it is not clear if a delayed
      introduction of ascorbate also yields beneficial effects. The main objective was
      to determine the therapeutic window for treatment of an animal model of sepsis
      with bolus injection of ascorbate. We also determined if sepsis per se affects
      urinary excretion of ascorbate. DESIGN: Prospective, controlled laboratory study.
      SETTING: Animal laboratory in a university-affiliated research institute.
      SUBJECTS: Male Sprague-Dawley rats, 300-400 g of body weight. INTERVENTIONS: Rats
      were made septic by cecal ligation and perforation (CLP) and volume resuscitated
      by continuous saline infusion. Ascorbate bolus (7.6 mg/100 g of body weight) or
      saline vehicle was injected intravenously at 1, 6, or 24 hrs after CLP.
      MEASUREMENTS AND MAIN RESULTS: At 24 hrs post-CLP, sepsis caused antidiuresis and
      decreased plasma ascorbate concentration, but it did not affect urinary excretion
      of ascorbate in rats that received only saline. Sepsis also caused
      maldistribution of capillary blood flow in skeletal muscle. This maldistribution
      of flow was prevented by ascorbate injected at 6 hrs post-CLP. At 48 hrs post
      CLP, in addition to the flow maldistribution, sepsis caused systemic arterial
      hypotension and fever that were prevented by both immediate (1 hr post-CLP) and
      delayed injections of ascorbate (24 hrs post-CLP). CONCLUSION: Despite volume
      resuscitation, the present model of sepsis resulted in maldistribution of
      capillary blood flow within 24 hrs and hypotension within 48 hrs. Our finding
      that intravenous bolus of ascorbate can protect against these deficits even if
      delayed 6-24 hrs after the septic insult shows, for the first time, that
      ascorbate can reverse microcirculatory dysfunction after the onset of sepsis.

PMID- 16096462
TI  - Post-thrombolysis intracerebral hemorrhage: data from the Spanish Register ARIAM.
AB  - OBJECTIVE: Our objective was to investigate the predisposing factors in patients
      with acute myocardial infarction (AMI) treated with thrombolysis and complicated
      by intracranial hemorrhage (ICH), as well as the factors associated with death
      for patients whose conditions were complicated by ICH. DESIGN: A retrospective
      study. SETTING: An intensive care/critical care unit. PATIENTS: All patients with
      AMI listed in the Spanish ARIAM register. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: The study period was from June 1996 to December 2003. The follow-up
      period was limited to the time spent in the intensive care unit/coronary care
      unit. Associations with the development of ICH were studied by univariate
      analysis. Another univariate analysis was used to evaluate the differences
      between patients affected by AMI complicated by ICH who died and those who
      survived. Two multivariate analyses were also used: one to evaluate the factors
      related to the development of ICH and the other to evaluate the factors
      associated with the death of patients with ICH. A total of 17,111 patients with
      AMI were included in the study. ICH occurred in 151 (0.9%) of these patients
      during their stay in the intensive care unit/coronary care unit. The multivariate
      analysis showed that the variables associated with ICH development were smoking
      (odds ratio [OR], 0.684; 95% confidence interval [CI], 0.478-0.979); oral b
      blockers (OR, 0.488; CI, 0.337-0.706); angiotensin-converting enzyme (ACE)
      inhibitors (OR, 0.480; CI, 0.340-0.678); arterial hypertension (OR, 4.900; CI,
      2.758-8.705); age of 55-64 yrs (OR, 2.253; CI, 1.117-4.546); age of 65-74 yrs
      (OR, 4.240; CI, 2.276-7.901); age of 75-84 yrs (OR, 4.450; CI, 2.319-8.539); and
      age of >84 yrs (OR, 2.997; CI, 1.039-8.647). The mortality rate among patients
      with ICH was 48.3%, vs. 8.3% among patients without ICH. The multivariate study
      showed that the mortality rate among patients with ICH was associated with age
      (OR, 1.086; CI, 1.033-1.143), arterial hypertension cardiovascular risk factor
      (OR, 2.773; CI, 1.216-6.324), and the need for mechanical ventilation (OR, 4.324;
      CI, 1.665-11.230) or cardiopulmonary resuscitation (OR, 12.258; CI, 1.268
      118.523). However, the administration of b-blockers (OR, 0.369; CI, 0.136-0.997)
      or ACE inhibitors (OR, 0.367; CI, 0.149-0.902) was associated with a reduction in
      the mortality rate. CONCLUSIONS: Factors associated with the development of ICH
      in our population were age and arterial hypertension, whereas smoking and the
      administration of b-blockers or ACE inhibitors were associated with a reduction
      in incidence. Among patients with AMI complicated by ICH, mortality was
      associated with age, arterial hypertension, cardiopulmonary resuscitation, and
      the use of mechanical ventilation, whereas the administration of oral b-blockers
      and ACE inhibitors could be associated with a reduction in mortality.

PMID- 16096464
TI  - Strategies to prevent antimicrobial resistance in the intensive care unit.
AB  - OBJECTIVE: To assemble the available clinical data for the prevention of
      antimicrobial resistance into practical recommendations for clinicians. DATA
      SOURCE: A Medline database and references from identified articles were employed
      to perform a literature search relating to the prevention of antimicrobial
      resistance. CONCLUSIONS: Antimicrobial resistance has emerged as an important
      determinant of mortality for patients in the intensive care unit. This is largely
      due to the increasing presence of pathogenic microorganisms with resistance to
      existing antimicrobial agents, resulting in the administration of inappropriate
      treatment. Effective strategies for the prevention of antimicrobial resistance
      within intensive care units are available and should be aggressively implemented.
      These strategies can be divided into nonpharmacologic infection control
      strategies (e.g., routine hand hygiene, implementation of infection-specific
      prevention protocols) and antibiotic management strategies (e.g., shorter courses
      of appropriate antibiotic treatment, narrowing of antimicrobial spectrum based on
      culture results). Increasing current efforts aimed at the prevention of
      antimicrobial resistance is especially important given the limited availability
      of new antimicrobial drug classes for the foreseeable future.

PMID- 16096463
TI  - Changes in the interleukin-6/soluble interleukin-6 receptor axis in meningococcal
      septic shock.
AB  - OBJECTIVE: Interleukin-6 is strongly associated with disease severity and outcome
      in meningococcal septicemia. It is known that interleukin-6 exerts many of its
      effects via the soluble interleukin-6 receptor. By facilitating the activity of
      interleukin-6, it is likely that alterations in the levels of soluble interleukin
      6 receptor in septic shock could affect the severity of disease. We aimed to
      investigate changes in the levels of interleukin-6 and soluble interleukin-6
      receptor in acute meningococcal septicemia and the relationship with disease
      severity. DESIGN: Laboratory investigation of interleukin-6 and soluble
      interleukin-6 receptor levels in children with meningococcal disease. SETTING:
      University hospital and laboratories. SUBJECTS: Children with severe
      meningococcal disease requiring intensive care. INTERVENTIONS: Blood samples
      obtained on admission to the intensive care unit were analyzed for interleukin-6
      and soluble interleukin-6 receptor levels. Levels were also serially measured for
      up to 48 hrs in a subset of patients. MEASUREMENTS AND MAIN RESULTS: Cytokine
      levels were measured by enzyme-linked immunosorbent assay using mouse monoclonal
      antihuman antibodies. Acute meningococcemia is associated with a reduction in
      soluble interleukin-6 receptor levels in proportion to disease severity and is
      inversely related to interleukin-6 levels. Soluble interleukin-6 receptor returns
      to levels seen in normal donors following recovery from meningococcal septicemia.
      CONCLUSIONS: Changes in the levels of interleukin-6 and soluble interleukin-6
      receptor in acute meningococcemia may affect the severity and progression of
      multiple organ failure. Interventions to modulate this axis may improve outcome
      from meningococcal septic shock.

PMID- 16096465
TI  - Spurious hypoxemia.
AB  - OBJECTIVE: To discuss the pathophysiology and clinical implications of spurious
      hypoxemia in the setting of hyperleukocytosis. DESIGN: Case report and review of
      the literature. SETTING: A 22-bed, adult neurosciences critical care unit at a
      tertiary care hospital. PATIENT: A 49-yr-old male with chronic myelogenous
      leukemia. INTERVENTIONS: Administration of hydroxyurea and imatinib mesylate.
      MEASUREMENTS AND MAIN RESULTS: The patient was admitted to the neurosciences
      critical care unit with an acute nontraumatic subdural hematoma that required
      emergent surgical evacuation. His clinical course was notable for neurologic
      deterioration, sepsis, hyperleukocytosis, severe hypoxemia, and prolonged
      mechanical ventilation. An inverse relationship was observed between arterial
      oxygen tension and the magnitude of hyperleukocytosis. Hypoxemia resolved after
      the institution of chemotherapy and normalization of white cell count. Pulse
      oximeter saturation was normal throughout. CONCLUSIONS: Patients with
      hyperleukocytosis are at risk for severe hypoxemia, which may be real or
      spurious. Failure to recognize spurious hypoxemia can lead to unnecessary
      diagnostic tests and therapeutic interventions, exposing patients to avoidable
      risk. A diagnostic algorithm is proposed.

PMID- 16096466
TI  - Fluid balance in acute lung injury: a model of clinical trial development.

PMID- 16096467
TI  - Lipoproteins are protective beyond high-density lipoprotein cholesterol and heart
      disease.

PMID- 16096468
TI  - How would Consumer Reports rate care in the intensive care unit?

PMID- 16096469
TI  - "Trip wires" in the trenches.

PMID- 16096470
TI  - Should emergency medical service rescuers be trained to practice endotracheal
      intubation?

PMID- 16096471
TI  - Nitrite therapeutics: back to the future.

PMID- 16096472
TI  - Can we take the teeth out of ventilator-associated pneumonia?

PMID- 16096473
TI  - Evoked-response testing for prognosis in anoxic-ischemic encephalopathy: a cool
      approach.

PMID- 16096474
TI  - The sirens are singing: the perils of trusting trials stopped early and subgroup
      analyses.

PMID- 16096475
TI  - Choose one: damned if you do/damned if you don't!

PMID- 16096476
TI  - Pleural effusions in the critically ill: the evolving role of bedside ultrasound.

PMID- 16096477
TI  - Ultrasound-guided central venous catheter placement: the new standard of care?

PMID- 16096478
TI  - Mechanistic approaches to acid aspiration and pneumonia must look beyond tumor
      necrosis factor-alpha levels.

PMID- 16096479
TI  - Soft tissue trauma: linking systemic hypothermia to sustained microvascular
      dysfunction.

PMID- 16096480
TI  - From scurvy to sepsis: vitamin C--A pill for all seasons?

PMID- 16096481
TI  - The ACE and smoke behind intracerebral hemorrhage.

PMID- 16096482
TI  - Myocardial dysfunction in meningococcal septic shock: no clear answer yet.

PMID- 16096484
TI  - Mechanically ventilated lung and response to pseudomonas aeruginosa.

PMID- 16096485
TI  - Use of goal-directed therapy for severe sepsis and septic shock in academic
      emergency departments.

PMID- 16096487
TI  - Surface cooling for fever control in brain-injured patients.

PMID- 16096488
TI  - Correct conclusions, but doubtful implications.

PMID- 16096490
TI  - Unrecognized peripartum cardiomyopathy.

PMID- 16096492
TI  - Is interleukin-6 clinically relevant?

PMID- 16096497
TI  - The use of radiation surveys to estimate the radiation effective dose to visitors
      of hospitalized patients--a theoretical study.
AB  - Members of the public visiting hospitalized patients undergoing nuclear medicine
      procedures or brachytherapy are exposed to radiation emanating from the patient.
      The radiation protection staff at the hospital is responsible for ensuring that
      the doses to these visitors are kept as low as is reasonably achievable and are
      maintained below applicable regulatory limits. These limits are normally
      expressed in terms of the effective dose to the visitor. Direct measurement of
      the effective dose, however, is not feasible, and the use of a quantity that
      provides a reasonable estimate, referred to as a surrogate, is required. This
      study used Monte Carlo radiation transport calculations to examine the
      feasibility of using bedside survey results, in units of roentgens per hour, as a
      surrogate for estimating the effective dose to a person who may be present at the
      survey location. The Monte Carlo code used in this work was MCNP Version 5. In
      these calculations, both the patient and the visitor were modeled using modified
      Medical Internal Radiation Dose anthropomorphic phantoms. Radioactive material
      that emitted monoenergetic photons was located in several of the patient's organs
      in turn, and the bedside exposure rates and the effective doses at the same
      location were calculated. The calculations were repeated for several visitor
      locations, both at bedside along the length of the bed, and at increasing
      distances from the bed. The ratios of the exposure rates to the effective dose
      rates at each location gave an indication of the utility of the exposure rate
      measurements in providing a reasonable estimate of the effective dose. The
      results indicated that the survey data provided estimates of the effective dose
      within recommended accuracy for many exposure situations, but underestimated the
      effective dose to the visitor for other situations, especially locations close to
      bedside and for lower energy radiations. Use of appropriate correction factors
      based on this work could improve the utility of the survey data for the
      underestimated situations, and the exposure rate data could still be used to
      estimate the dose to a visitor within recommended accuracy, provided the
      estimated dose does not approach too closely to the applicable limit.

PMID- 16096496
TI  - A comparison of skeletal chord-length distributions in the adult male.
AB  - In radiation protection, skeletal dose estimates are required for the tissues of
      the hematopoietically active bone marrow and the osteogenic cells of the
      trabecular and cortical endosteum. Similarly, skeletal radiation dose estimates
      are required in therapy nuclear medicine in order to develop dose-response
      functions for myelotoxicity where active bone marrow is generally the dose
      limiting organ in cancer radioimmunotherapy. At the present time, skeletal dose
      models in both radiation protection and medical dosimetry are fundamentally
      reliant on a single set of chord-length distribution measurements performed at
      the University of Leeds in the late 1970's for a 44-y-old male subject. These
      distributions describe the relative frequency at which linear pathlengths are
      seen across both the marrow cavities and bone trabeculae in seven individual bone
      sites: vertebrae (cervical and lumbar), proximal femur (head and neck), ribs,
      cranium (parietal bone), and pelvis (iliac crest). In the present study, we
      present an alternative set of chord-length distribution data acquired within a
      total of 14 skeletal sites of a 66-y-old male subject. The University of Florida
      (UF) distributions are assembled via 3D image processing of microCT scans of
      physical sections of trabecular spongiosa at each skeletal site. In addition, a
      tri-linear interpolation Marching Cube algorithm is employed to smooth the
      digital surfaces of the bone trabeculae while chord-length measurements are
      performed. A review of mean chord lengths indicate that larger marrow cavities
      are noted on average in the UF individual for the cervical vertebrae (1,038 vs.
      910 microm), lumbar vertebrae (1,479 vs. 1,233 microm), ilium (1,508 vs. 904
      microm), and parietal bone (812 vs. 389 microm), while smaller marrow cavities
      are noted in the UF individual for the femoral head (1,043 microm vs. 1,157
      microm), the femoral neck (1,454 microm vs. 1,655 microm), and the ribs (1,630
      microm vs. 1,703 microm). The mean chord-lengths for the bone trabeculae show
      close agreement for both individuals in the ilium (approximately 240 microm) and
      cervical vertebrae (approximately 280 microm). Thicker trabeculae were seen on
      average in the UF individual for the femoral head (ratio of 1.50), femoral neck
      (ratio of 1.10), lumbar vertebrae (ratio of 1.29), and ribs (ratio of 1.14),
      while thinner trabeculae were seen on average in the UF individual for the
      parietal bone of the cranium (ratio of 0.92). In two bone sites, prominent
      discrepancies in chord distribution shape were noted between the Leeds 44-y-old
      male and the UF 66-y-old male: (1) the bone trabeculae in the ribs, and (2) the
      marrow cavities and bone trabeculae within the cranium.

PMID- 16096498
TI  - Abnormal responses of electronic pocket dosimeters caused by high frequency
      electromagnetic fields emitted from digital cellular telephones.
AB  - High frequency electromagnetic fields emitted from digital cellular telephones
      (cell phones) occasionally cause abnormally high and erroneous indicated dose
      readings on electronic pocket dosimeters (EPDs). Electric field strength
      distribution around a cell phone transmitting 1.5 GHz band with a maximum power
      of 0.8 W was analyzed by using an isotropic probe with tri-axial dipole antennas.
      Five types of EPDs were exposed to the fields for 50 s under configurations
      relative to the cell phone. The electric field distribution expanded around the
      phone's antenna and had a maximum electric field strength of 36.5 +/- 0.3 V m(
      1). The cell phone gave rise to erroneous indicated dose readings on four out of
      five EPDs. The maximum value of erroneous indicated dosage for 50 s reached 1,283
      microSv, which was about 2.6% of the annual effective dose limit of 50 mSv. The
      electromagnetic susceptibility of the EPDs was higher in the sections where the
      semiconductor detectors or electric circuit boards were located. The distance
      required to prevent electromagnetic interference differed for each EPD and ranged
      from 2.0 to 21.0 cm from the cell phone. The electric and magnetic field immunity
      levels of the EPDs varied from 9.2 V m(-1) to greater than 37.6 V m(-1), and from
      0.03 A m(-1) to greater than 0.51 A m(-1). The EPDs displayed erroneous dose
      readings during exposure but recovered their normal performance after the cell
      phone ceased transmitting. The electromagnetic immunity levels of the EPDs were
      either equal to or greater than the IEC-standard. The immunity levels should be
      enhanced greater than the IEC-standard from the standpoint of radiation
      protection. The simplest and most reliable measure to prevent potential
      malfunction is to prohibit the radiation workers from carrying cell phones to
      their workplace.

PMID- 16096499
TI  - Retrospective luminescence dosimetry: development of approaches to application in
      populated areas downwind of the Chernobyl NPP.
AB  - The cumulative absorbed dose in fired-clay bricks collected from ten buildings in
      the populated contaminated settlement (137Cs, 1,470 kBq m(-2)) of Stary Vishkov,
      located 175 km downwind of the Chernobyl Nuclear Power Plant (NPP) in the Bryansk
      administrative region of Russia, was determined using luminescence techniques by
      five laboratories. At each location, the cumulative dose, after subtraction of
      the natural background dose, was translated to absorbed dose in air using
      conversion factors derived from Monte Carlo simulations. The simulations employed
      source distributions inferred from contemporary soil contamination data and also
      took into account heterogeneity of fallout deposition. At four locations the
      cumulative dose at a reference location was calculated, enabling the luminescence
      determinations to be compared directly with values of cumulative absorbed dose in
      air obtained using deterministic models. A "local" conversion factor was also
      derived from the Monte Carlo simulations for locations where the disturbance of
      soil was significant. Values of the "local" cumulative dose in air calculated
      using this factor were compared with those predicted using the deterministic
      models at each sampled location, allowing location factors to be calculated. The
      methodology developed is generally applicable to populated areas contaminated by
      radioactive fallout in which brick buildings are found. The sensitivity of the
      luminescence techniques for bricks from this region of Russia was sufficient to
      evaluate cumulative absorbed dose in brick due to fallout of less than 20 mGy.

PMID- 16096500
TI  - Calculation of immersion doses from external exposure to a plume of radioactive
      material.
AB  - The immersion doses from external exposure to a Gaussian plume of noble gases
      accidentally released into the atmosphere have been calculated. A numerical
      integration procedure employing Gauss-Legendre of 64th order has been used. The
      numerical procedure allows calculating the dose rate at any downwind horizontal
      or vertical distance. The dose rates were calculated using various forms of gamma
      dose build-up factors, including Linear, Berger and Geometric Progression (GP).
      The GP form, having an extraordinarily precise formulation, is a favored choice
      because the build-up factor levels off for large distances and does not increase
      exponentially as does the Berger form. The Linear form much under predicts the
      build-up and subsequently the dose rates for large distances from the source. The
      dose predictions using a simple uniform cloud model (that does not use any form
      of build-up factor) is also presented for comparison purposes. The comparison of
      dose rates with the already reported results indicated that the numerical
      procedure could be used for dose calculations from a Gaussian plume for all
      downwind and crosswind distances. The comparison of dose rates obtained using
      different forms of the build-up factors indicated that the Geometric Progression
      form was a favored choice and has a wider range of applicability as compared to
      the Linear or Berger form. The simple uniform cloud model for dose calculations
      is only suitable for plume centerline doses and should be used with caution for
      off-center distances.

PMID- 16096501
TI  - Plutonium contamination in soils and sediments at Mayak PA, Russia.
AB  - The Mayak Production Association (Mayak PA) was established in the late 1940's to
      produce plutonium for the Soviet Nuclear Weapons Programme. In total, seven
      reactors and two reprocessing plants have been in operation. Today, the area
      comprises both military and civilian reactors as well as reprocessing and
      metallurgical plants. Authorized and accidental releases of radioactive waste
      have caused severe contamination to the surrounding areas. In the present study,
      [alpha]-spectrometry and inductively coupled plasma-mass spectrometry (ICP-MS)
      have been used to determine plutonium activities and isotope ratios in soil and
      sediment samples collected from reservoirs of the Techa River at the Mayak area
      and downstream Techa River. The objective of the study was to determine the total
      inventory of plutonium in the reservoirs and to identify the different sources
      contributing to the plutonium contamination. Results based on [alpha]
      spectrometry and ICP-MS measurements show the presence of different sources and
      confirmed recent reports of civilian reprocessing at Mayak. Determination of
      activity levels and isotope ratios in soil and sediment samples from the Techa
      River support the hypothesis that most of the plutonium, like other radionuclides
      in the Techa River, originated from the very early waste discharges to the Techa
      River between 1949 and 1951. Analysis of reservoir sediment samples suggest that
      about 75% of the plutonium isotopes could have been released to Reservoir 10
      during the early weapons production operation of the plant, and that the majority
      of plutonium in Reservoir 10 originates from discharges from power production or
      reprocessing. Enhanced 240Pu/239Pu atom ratios in river sediment upper layers (0
      2 cm) between 50 and 250 km downstream from the plant indicate a contribution
      from other, non-fallout sources.

PMID- 16096502
TI  - Prediction of renal concentrations of depleted uranium and radiation dose in Gulf
      War veterans with embedded shrapnel.
AB  - Mobilization of uranium (U) from embedded depleted uranium (DU) metal fragments
      in Gulf War veterans presents a unique exposure scenario for this radioactive and
      nephrotoxic metal. In a cohort of exposed veterans, urine U concentrations
      measured every two years since 1993 persistently range from 10 to over 500 times
      normal levels, indicating that embedded DU fragments give rise to chronic,
      systemic exposure to U. Health effects of this exposure are not fully known, but
      clinical surveillance of these soldiers continues in light of animal studies
      showing that U released from implanted DU pellets results in tissue accumulation
      of U. The biokinetic model for uranium recommended by the International
      Commission on Radiological Protection was used to predict kidney U concentrations
      and tissue radiation doses in veterans with DU shrapnel based on their urine U
      excretion. Results suggest that kidney U concentrations in some individuals
      reached their peak within six years after the war, while in others,
      concentrations continue to increase and are approaching 1 ppm after 10 y. These
      results are consistent with urine biomarker tests of renal proximal tubular cell
      function and cytotoxicity which have shown elevated mean urinary protein
      excretion indicative of functional effects in veterans with high urine U
      concentrations (> or =0.10 microg g(-1) creatinine). Predicted lifetime effective
      radiation dose from DU released to the blood for the highest exposed individual
      in this cohort was substantially less than the National Council on Radiation
      Protection (NCRP) limit for occupational exposure. These results provide further
      support for current health protection guidelines for DU, which are based on the
      metal's chemical rather than its radiological toxicity. In light of the potential
      for continued accumulation of U in the kidney to concentrations approaching the
      traditional guidance level of 3 ppm U, these results indicate the need for
      continued surveillance of this population for evidence of developing renal
      dysfunction.

PMID- 16096504
TI  - Comments on the article "Possible contribution of 129I in the drinking water and
      food supply to the nodular formation of thyroid tissue".

PMID- 16096505
TI  - Radiological assessment of petroleum pipe scale from pipe-rattling operations.

PMID- 16096507
TI  - Comment on Dogru paper. "Possible contribution of 129I in the drinking water and
      food supply to the nodular formation of thyroid tissue".

PMID- 16096509
TI  - Nonmelanoma gingival malignancies and tooth loss among beagles injected with
      90Sr.

PMID- 16096514
TI  - Antipsychotic drugs and QT prolongation.
AB  - Antipsychotic drugs (AD) are effective and frequently prescribed to more females
      than males. AD may cause serious cardiovascular side-effects, including prolonged
      QT interval, eventually leading to torsades de pointes (TdP) and sudden death.
      Epidemiologic data and case-control studies indicate an increased rate of sudden
      death in psychiatric patients taking AD. This review summarizes current knowledge
      about the QT prolonging effects of AD and gives practical suggestions.
      Amisulpride, clozapine, flupenthixol, fluphenazine, haloperidol, melperone,
      olanzapine, perphenazine, pimozide, quetiapine, risperidone, sulpiride,
      thioridazine and ziprasidone cause a QT prolongation ranging from 4 ms for
      risperidone to 30 ms for thioridazine. Our knowledge about the QT-prolonging
      effects of many AD is still limited. Females are under-represented in most
      studies. Many studies were conducted or supported by pharmaceutical companies. To
      avoid prodysrhythmia caused by QT prolongation, other factors influencing QT
      interval have to be considered, such as other drugs affecting the same pathway,
      hypokalemia, hypomagnesemia, bradycardia, increased age, female sex, congestive
      heart failure and polymorphisms of genes coding ion channels or enzymes involved
      in drug metabolism. Because the response of a patient to AD is individual, an
      electrocardiogram recording the QT interval has to be performed at baseline,
      after AD introduction and after occurrence of any factor that might influence the
      QT interval.

PMID- 16096515
TI  - Mirtazapine in amphetamine detoxification: a placebo-controlled pilot study.
AB  - The present study aimed to assess the safety and efficacy of mirtazapine in
      amphetamine detoxification in a 14-day randomized, placebo-controlled pilot trial
      in a Thai population. Subjects retained at a Specialized Probation Center,
      Department of Probation, Ministry of Justice, Thailand (n=20), who met DSM-IV
      criteria for amphetamine dependence and the inclusion criteria of the study, were
      randomized for either mirtazapine treatment or placebo. Efficacy was assessed by
      the Amphetamine Withdrawal Questionnaire (AWQ) for amphetamine withdrawal
      symptoms and the Montgomery-Asberg Depression rating scale (MADRS) for
      depression. Mirtazapine safety was assessed by interview during each follow-up
      period on days 3 and 14 after treatment. Nine subjects were randomized to the
      mirtazapine group and 11 to the placebo group. Among the initial 20 subjects, 16
      (seven in the mirtazapine and nine in the placebo group) completed the study.
      There were significant improvements in the total AWQ score changes in the
      mirtazapine group versus placebo both at days 3 (P<0.005) and 14 (P<0.030).
      Significant improvements in favour of mirtazapine were also seen in the
      hyperarousal and the anxiety subscale score changes at days 3 (P<0.029) and 14
      (P<0.018), respectively. No significant differences were seen (P>0.05) in the
      MADRS scores changes within or between the groups. Mild adverse events, such as
      headache, sedation, nausea and vomiting, were reported. In conclusion, despite
      its small sample size, this randomized, placebo-controlled pilot trial lends
      support to the hypothesis that mirtazapine may be an option in the meager
      armamentarium of amphetamine detoxification treatment.

PMID- 16096516
TI  - Fluoxetine monotherapy of bipolar type II and bipolar NOS major depression: a
      double-blind, placebo-substitution, continuation study.
AB  - Current guidelines for the treatment of bipolar type II (BP II) major depressive
      episode (MDE) recommend using either mood stabilizer monotherapy or the
      combination of a mood stabilizer with a selective serotonin reuptake inhibitor
      (SSRI). These guidelines are the result of concern over SSRI-induced manic switch
      episodes. We previously showed that fluoxetine monotherapy may be effective as an
      initial treatment for BP II and BP NOS MDE with a low manic switch rate. We now
      present the results of a double-blind, placebo-substitution continuation study of
      fluoxetine monotherapy in BP II and BP NOS patients who have recovered from their
      MDE. This was a two-phase study. In study phase I, patients received open-label
      fluoxetine monotherapy 20 mg daily for up to 8 weeks. Responders with a final 17
      item Hamilton Rating Scale for Depression (HAM-D) score < or =9 were enrolled
      into study phase II which consisted of double-blind, placebo-substitution
      continuation therapy with fluoxetine 20 mg daily for up to 6 months. Outcome
      measures included the 17-item HAM-D and Young Mania Rating (YMR) scales. Changes
      in YMR scores were assessed using generalized estimating equation analysis.
      Relapse was assessed using Kaplan-Meier survival analysis and Fisher's exact
      test. In study phase II, 43% of fluoxetine-treated patients and 100% of placebo
      treated patients relapsed during continuation therapy (P=0.08). The mean increase
      in YMR score in study phase II was slightly higher in the fluoxetine-treated
      patients (3.0+/-1.8) versus placebo-treated patients (0.2+/-0.4) (P=0.01).
      However, this difference was not clinically meaningful. No hypomanic switch
      episodes were observed during study phase II. Despite the limited sample size
      resulting in insufficient power to detect statistical significance in relapse
      rates or change in YMR scores between treatment conditions, these preliminary
      data appear to support previous observations demonstrating that initial and
      continuation fluoxetine monotherapy may be safe and effective for some patients
      with BP II or BP NOS MDE with a low manic switch rate. Larger-scale studies are
      needed to confirm these findings.

PMID- 16096517
TI  - A placebo-controlled, randomized withdrawal study of sertraline for panic
      disorder in Japan.
AB  - The objective of this double-blind, placebo-controlled randomized withdrawal
      study was to evaluate the efficacy and safety of sertraline for 8 weeks in
      treating Japanese patients with DSM-IV panic disorder. Patients (n=394) were
      initially treated with 8 weeks of open-label sertraline followed by 8 weeks of
      double-blind treatment with either sertraline (50-100 mg/day) or placebo.
      Responders during the open-label phase were eligible to be entered into the
      double-blind phase. Two hundred and forty patients were entered to the double
      blind phase and randomly assigned to receive sertraline (n=119) or placebo
      (n=121). On the primary efficacy measure (relapse), there was no significant
      difference between the two treatment groups (sertraline 10.1%; placebo 13.2%).
      However, the frequency of panic attacks was significantly (P=0.012) lower for
      sertraline compared to placebo. The proportion of sertraline-treated patients who
      met response criteria (Clinical Global Impression-Improvement Scale score of 1 or
      2) at the end of double-blind phase treatment was also significantly (P=0.003)
      higher for sertraline (89.9%) compared to placebo (74.4%). Panic Disorder
      Severity Scale total score was significantly (P=0.012) lower in the sertraline
      group compared to the placebo group. Adverse events during acute treatment were
      consistent with the known adverse event profile of sertraline, and the incidence
      of adverse events during the double-blind phase treatment was not different
      between sertraline and placebo.

PMID- 16096518
TI  - Risperidone reduces aggression in boys with a disruptive behaviour disorder and
      below average intelligence quotient: analysis of two placebo-controlled
      randomized trials.
AB  - The present study aimed to analyse the effect of risperidone on a priori defined
      core aggression items. Data were pooled from 163 boys (aged 5-12 years, with or
      without comorbid attention-deficit/hyperactivity disorder) with a DSM-IV
      diagnosis of either conduct disorder or oppositional defiant disorder who had
      participated in either of two identical, 6-week, randomized, double-blind,
      placebo-controlled trials. All received treatment with either placebo or oral
      risperidone solution (0.01-0.06 mg/kg/day). Subjects had below average
      intelligence [intelligence quotient (IQ) 36-84] and a score of > or =24 on the
      Conduct Problem subscale of the Nisonger Child Behaviour Rating Form (N-CBRF). An
      expert advisory panel selected six core aggression items from the N-CBRF, from
      which a total Aggression Score (AS, range 0-18) was constructed. Compared to
      those treated with placebo, risperidone-treated subjects experienced
      significantly greater mean decreases from baseline in the AS at each of weeks 1-6
      (P<0.001). By study endpoint, aggression among risperidone-treated subjects had
      declined by 56.4% (mean baseline AS 10.1; mean endpoint AS 4.4), which was more
      than twice that of placebo-treated subjects (mean baseline AS 10.6; mean endpoint
      AS 8.3; 21.7% reduction). Risperidone was efficacious in reducing symptoms of
      aggression in boys of below average IQ with disruptive behaviour disorders.

PMID- 16096519
TI  - Dependence on zolpidem: two case reports of detoxification with flumazenil
      infusion.
AB  - Zolpidem is a hypnotic drug that is chemically distinct from benzodiazepines
      (BDZ). It has been suggested that it acts selectively on gamma-aminobutyric acid
      receptors. However, recent evidence has shown that the behavioural effects of
      zolpidem are generally similar to those of BDZs. Flumazenil is usually considered
      to be a BDZ antagonist. Nonetheless, in chronic BDZ users, it acts as a partial,
      bland agonist. We describe two cases of zolpidem dependence that were detoxified
      by the use of flumazenil infusion. BDZ dependence is usually treated with
      tapering of the medication. As an alternative, abrupt discontinuation of the
      medication and rapid detoxification using flumazenil has been used. Flumazenil
      may represent an alternative to detoxification treatment by employing a tapering
      approach, or by replacement therapy with BDZs with a long half-life, particularly
      where patients are hard to treat or have low compliance to treatment.

PMID- 16096520
TI  - Major depressive episode with psychotic features induced by pegylated interferon
      alpha-2b and ribavirin treatment.
AB  - Recent evidence has demonstrated the efficacy of pegylated interferon-alpha (IFN
      alpha) in treating hepatitis C virus infection. Neuropsychiatric complications
      commonly occur during the course of IFN treatment, with depressive symptoms
      usually appearing within the first 12 weeks. Few cases of the pegylated
      interferon-alpha-induced psychosis and depression have been reported compared to
      standard interferon-alpha therapy. We report the first case of a major depressive
      episode with psychotic features induced by pegylated IFN-alpha-2b and ribavirin
      in the last 2 weeks of therapy.

PMID- 16096521
TI  - Cytomegalovirus reactivation in pediatric hemopoietic progenitors transplant: a
      retrospective study on the risk factors and the efficacy of treatment.
AB  - Cytomegalovirus (CMV) disease is an important infectious complication after
      allogeneic hemopoietic progenitors transplant (HPT), but few data are available
      in children. To investigate the factors influencing CMV reactivation, subsequent
      relapses of positive antigenemia, and the development of organ disease in
      children, the authors retrospectively analyzed 108 children who received
      allogeneic HPT for malignant conditions at one center. Of these, 41 were CMV
      serology positive (donor or recipient) before HPT. All those with CMV-positive
      serology received high-dose acyclovir in conjunction with weekly CMV
      phosphoprotein-pp65 antigen monitoring of the peripheral blood during the first 3
      months. Those with CMV reactivation (positive antigenemia) received preemptive
      treatment with ganciclovir and/or foscarnet to prevent CMV disease. The incidence
      of positive antigenemia in this cohort was 41.5% at a mean of 44 +/- 31.6 days
      after HPT. Two patients (4.9%) subsequently developed late CMV disease. Recipient
      CMV status was significantly (P = 0.0001) more relevant to reactivation than
      donor status. Reactivations were significantly more common in single recipient
      seropositive than double (donor and recipient) positive pairs (P = 0.05).
      Reactivations were significantly more common in recipients of unrelated donor
      grafts than matched-related donor grafts (P = 0.025). Reactivations also occurred
      significantly more in T-cell-depleted graft recipients (P = 0.004) than
      recipients of unmanipulated grafts. The subsequent development of disease was
      more common in a CMV-seropositive recipient receiving a CMV-seronegative, T-cell
      depleted, unrelated donor graft, and after transplantation receiving treatment
      for acute graft-versus-host disease. Patients with identified high risk factors
      for CMV reactivation and disease should be monitored by CMV PCR, and early
      preemptive treatment should be instigated to prevent the development of disease.

PMID- 16096522
TI  - Clinical and laboratory manifestations of congenital dyserythropoietic anemia
      type I in a cohort of French children.
AB  - Congenital dyserythropoietic anemia type I (CDA I) is a rare disorder of
      erythropoiesis. The objective of this study was to describe the clinical and
      laboratory manifestations, the diagnosis procedure, the therapeutic approaches
      and outcome in CDA I. The 12 patients included belong to the retrospective French
      Multicenter Study. Clinical and biologic data were compiled. Biologic tests
      included light and, in some cases, electron microscopy, ektacytometry, and red
      cell membrane protein electrophoresis. Neonatal manifestations (anemia, early
      jaundice, and/or splenomegaly) and bone abnormalities were present in 11 of the
      12 and 6 of the 12 patients, respectively. CDA I was initially misdiagnosed in
      four children. By the time of diagnosis, anemia with reticulocytosis lower than
      expected in a hemolytic anemia was present in all patients. Bone marrow electron
      microscopy examination revealed characteristic findings in all nine children. Red
      cell membrane protein 4.1 was reduced in all five children. At least one
      transfusion was required in 11 of the 12 children. Interferon alpha2 corrected
      anemia in the three children who received monthly transfusions. CDA I is commonly
      misdiagnosed in children. It should be sought in patients with unexplained
      chronic anemia, especially when associated with neonatal manifestations,
      jaundice, splenomegaly, subnormal or low reticulocytosis, and congenital bone
      malformations.

PMID- 16096523
TI  - Headache symptoms in pediatric sickle cell patients.
AB  - The purposes of this study were to determine the characteristics of headaches in
      children with sickle cell disease (SCD) and to assess the relationship between
      headache symptoms and children's physical and emotional status. A detailed
      headache questionnaire using International Classification of Headache Disorders
      (ICHD-2) criteria was mailed to a cohort (n = 50) of children with SCD, ages 9 to
      17 years. Respondents also completed measures of functional disability and
      psychological distress. Headaches had occurred over the previous 3-month period
      in 76.2% of the patients. Frequent headaches were common, occurring greater than
      once a week in 31.2% of children. Average pain severity was reported as moderate
      on a 0-to-10 scale (mean = 5.8). Duration of headaches ranged from 30 minutes to
      several days, with a mean of 5 hours. Based on ICHD-2 criteria, 43.8% of children
      had headache symptoms consistent with migraines, 6.2% with migraine with aura,
      and 50.0% with tension-type headaches. Children with symptoms of migraine had
      significantly greater functional disability compared with children with symptoms
      of tension-type headaches (P < 0.01). Further studies to determine the
      characteristics and determinants of headaches experienced in SCD patients will
      help maximize treatment of headaches and enhance daily functioning in these
      patients.

PMID- 16096524
TI  - The MTHFR C677T and A1298C polymorphisms and susceptibility to childhood acute
      lymphoblastic leukemia in Portugal.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate
      metabolism and in DNA methylation and synthesis. The role of two common
      polymorphisms at the MTHFR gene, C677T and A1298C, in the etiology of childhood
      or adult acute lymphoblastic leukemia (ALL) has been previously investigated.
      Although a protective effect of MTHFR*677T against ALL was systematically
      reported, the magnitude of the effect appeared to be influenced by population
      specific gene-environmental interactions. The evidence of the role of MTHFR*1298C
      in ALL susceptibility was less consistent, emphasizing the need for enlarging
      molecular epidemiologic studies to independent trials from different populations.
      The authors analyzed in North Portugal the association between variations at the
      two MTHFR positions and risk of ALL by comparing genotypes and gene frequencies
      in 103 affected children with those in 111 healthy controls. None of the
      variations was found to significantly affect the risk of developing childhood ALL
      in North Portugal, and this finding per se is of relevance in further studies
      aimed at assessing the etiology of the pathology in this specific population.
      Despite the absence of statistical significance, these data revealed that the
      frequency of MTHFR*677T was lower in patients than in controls, a result that is
      congruent with other reports and with the functional model usually invoked to
      explain its ALL protective effect. Concerning MTHFR1298*C, this study failed to
      corroborate previous findings of decreased risk of ALL in the presence of the
      variant.

PMID- 16096525
TI  - Rubella-associated hemophagocytic syndrome in an infant.
AB  - Hemophagocytic syndrome (HPS) is a fulminant disorder characterized
      pathologically by multiple-organ infiltration of hemophagocytic histiocytes in
      the lymphoreticular tissues. The characteristic pathologic feature is reactive
      histiocytic hyperplasia with leukoerythrophagocytosis in a variety of organs.
      This disorder occurs most often in patients in whom the immune system is
      compromised and has been associated with a variety of infectious agents,
      including viruses, bacteria, mycobacteria, spirochetes, fungi, and parasites. The
      authors describe a 2.5-month-old girl with rubella-associated HPS, demonstrated
      by postmortem liver necropsy.

PMID- 16096526
TI  - Defining the role of magnetic resonance imaging in unifocal bone lesions of
      langerhans cell histiocytosis.
AB  - Localized Langerhans cell histiocytosis (LCH) of bone often presents as a
      diagnostic challenge. Magnetic resonance imaging (MRI) is frequently used to
      better delineate most solitary bony lesions. The authors present two cases that
      illustrate and better define the role of MRI in the evaluation of solitary bone
      lesions of LCH. In a 3-year-old boy with left-sided hip pain, MRI showed a focal
      lesion involving the proximal left femur with low signal intensity on T1-weighted
      images and high signal intensity on T2-weighted images. A tumor was suspected
      because of the overall imaging characteristics and increased uptake on three
      phase nuclear scintigraphy. In a 6-year-old boy with right thigh pain, MRI showed
      a fluid-containing lesion in the mid-diaphysis of the right femur, suggestive of
      chronic osteomyelitis and Brodie abscess. MRI was instrumental in showing the
      extent of the lesions in both cases; however, the final diagnosis of LCH was
      achieved only with histopathologic confirmation, illustrating the limited
      diagnostic power of this imaging tool.

PMID- 16096527
TI  - Moyamoya syndrome associated with hemolytic anemia due to Hb Alesha.
AB  - Moyamoya angiopathy is a well-known complication of sickle cell disease but has
      rarely been observed in other hemoglobinopathies. The authors describe a
      previously unreported association of hemolytic anemia due to a rare unstable
      hemoglobinopathy with abnormal oxygen affinity (Hb Alesha) and moyamoya syndrome
      in a 10-year-old girl. At age 4 she had recurrent migraine-with-aura-like
      symptoms. Cranial MRI, Doppler, and EEG examinations were not conclusive.
      Deterioration of her neurologic symptoms prompted a renewed EEG examination at 10
      years of age, which revealed a re-buildup phenomenon. MRI and MR angiography now
      showed moyamoya angiopathy with stenotic and occlusive lesions of both internal
      carotid and middle cerebral arteries. Conventional angiography confirmed these
      findings. Reperfusion with three extra-intracranial bypasses terminated the
      transient ischemic attacks. The authors suggest that chronic hypoxemia may be the
      cause of occlusive moyamoya angiopathy in Hb Alesha and possibly other unstable
      hemoglobinopathies with altered oxygen affinity.

PMID- 16096528
TI  - Germline p53 mutation presenting as synchronous tumors.
AB  - Li-Fraumeni syndrome and the LF-like syndrome, rare heritable conditions that
      predispose to the development of malignancy, are associated with germline
      mutations of the tumor suppressor gene p53. The authors describe a 14-month-old
      boy who presented with synchronous rhabdomyosarcoma and adrenal cortical
      carcinoma and a novel mutation of the p53 gene. Analysis of exons 2 through 11 of
      the p53 gene using the polymerase chain reaction and DNA sequencing revealed a
      mutation of codon 273. Although codon 273 is a known hotspot region for p53
      mutation, the patient's mutation, R273H, has not been associated with development
      of adrenal cortical carcinoma.

PMID- 16096529
TI  - Proton beam irradiation in pediatric oncology: an overview.
AB  - The greatest challenge for the treatment of children with cancer is to attain the
      highest probability of cure with the least morbidity. This has stimulated
      advances in radiotherapy technology. In recent literature published regarding
      proton radiation therapy (PRT) for pediatric cancer patients, PRT has been shown
      to have a distinct advantage over conventional photon therapy because of the
      ability to confine the high-dose treatment area to the tumor volume and minimize
      the radiation dose to the surrounding tissue. This is particularly important in
      children, in whom late effects of radiation to normal tissue can include
      developmental delay and increased risk of second malignant neoplasms. Several
      proton facilities are operating world-wide, and several medical centers in the
      United States and Europe are in the midst of planning and constructing new proton
      facilities. This may enlarge the role of radiation therapy in the multimodal
      management of children with cancer.

PMID- 16096530
TI  - Once-per-cycle pegfilgrastim versus daily filgrastim in pediatric patients with
      Ewing sarcoma.
AB  - The use of the recombinant human granulocyte colony-stimulating factor filgrastim
      to shorten the duration of severe neutropenia after cytotoxic chemotherapy has
      become an integral part of supportive care. However, due to its short serum half
      life, filgrastim must be injected daily. Pegfilgrastim, a new long-lasting form
      of filgrastim administrated once per cycle, has been shown in adults to be as
      effective in reducing the duration of severe neutropenia as daily filgrastim. The
      aim of this study was to evaluate the effects of pegfilgrastim in pediatric
      patients. Five children with Ewing sarcoma were alternately treated with a single
      100 microg/kg pegfilgrastim dose or daily doses of 10 microg/kg Filgrastim after
      a total number of 58 chemotherapy cycles. Pegfilgrastim was well tolerated. The
      duration of severe neutropenia and the incidence of febrile neutropenia after
      pegfilgrastim and filgrastim were comparable. By using pegfilgrastim, the number
      of subcutaneous injections could be reduced to one single injection per cycle.

PMID- 16096531
TI  - The bioexpandable prosthesis: a new perspective after resection of malignant bone
      tumors in children.
AB  - Bone reconstruction after resection of malignant bone tumors of the lower
      extremity in children and adolescents remains a challenge in limb-sparing
      surgery. Equal limb length at maturity and good functional outcome are the main
      goals of these surgeries but often are difficult to achieve. Expandable
      endoprostheses are available but usually require repeated operative interventions
      for lengthening. Moreover, as the size of the implant increases, the proportion
      of the implant relative to the remaining bone increases, generating a
      biomechanical disadvantage to the limb. The authors describe a new concept
      combining an endoprosthesis with a fully implantable motorized distraction nail
      that can be activated in gradual steps to lengthen the remaining bone by callus
      distraction. New high-quality bone is growing and the proportion of prosthesis
      length compared with leg length develops in favor of the remaining bone.

PMID- 16096532
TI  - Trauma/critical care surgeon: a specialist gasping for air.
AB  - BACKGROUND: In the last 10 years, trauma/critical care has become less attractive
      because of the decreasing surgical caseload, the nocturnal work hours, and the
      economics of the practice. Nevertheless, during the same period, the number of
      verified trauma centers has significantly increased. This study assesses the
      economic drive behind this dichotomy. METHODS: Over a 1-year period, we collected
      financial data on 1,907 trauma patients for both Level I trauma centers and
      trauma/critical care surgeons. Financial data, including payor source, cost,
      reimbursement, margin, and reimbursement-to-charge and reimbursement-to-direct
      cost ratios, were calculated. RESULTS: For commercial- and government-insured
      patients, the reimbursement-to-direct cost ratio was 2-and 35-fold greater,
      respectively, for the trauma centers than for the trauma/critical care surgeons.
      For uninsured patients, the addition of local government funds allowed the trauma
      center to cover direct cost with no margin. In contrast, even with the addition
      of supplemental salary dollars from the institution, for every dollar in direct
      cost generated by the trauma/critical care surgeons in caring for uninsured
      patients, they recovered 55 cents, or a loss of 45 cents per direct cost dollar
      spent. CONCLUSION: The economic dichotomy that exists between trauma centers and
      trauma/critical surgeons is significant. It drives institutional growth and, at
      the same time, discourages surgeons from entering the subspecialty. As physician
      reimbursement decreases and the number of uninsured patients increases, this
      economic dichotomy will amplify. Over the next decade, without a significant
      adjustment, the subspecialty is in danger of extinction.

PMID- 16096534
TI  - Transfusions result in pulmonary morbidity and death after a moderate degree of
      injury.
AB  - BACKGROUND: Prior studies have suggested that blood transfusion (Tx) is
      associated with infectious and respiratory complications in trauma patients.
      However, these studies are difficult to interpret because of small sample size,
      inclusion of severely injured patients in traumatic shock, and combination of a
      variety of unrelated low-morbidity/mortality infections, such as wound, catheter
      related, and urinary tract infection as outcomes. To eliminate these confounding
      variables, this study evaluates the association between delayed Tx and serious,
      well-defined respiratory complications (ventilator-associated pneumonia [VAP] and
      acute respiratory distress syndrome [ARDS]) and death in a cohort of intensive
      care unit (ICU) admissions with less severe (Injury Severity Score [ISS] < 25)
      blunt trauma who received no Tx within the initial 48 hours after admission.
      METHODS: Patients with blunt injury and ISS < 25 admitted to the ICU over a 7
      year period were identified from the registry and excluded if within 48 hours
      from admission they received any Tx or if they died. VAP required quantitative
      bronchoalveolar lavage culture (> or =10(5) colonies/mL), and ARDS required
      Pao2/Fio2 ratio < 200 mm Hg, *** no congestive heart failure, diffuse bilateral
      infiltrates, and peak airway pressure > 50 cm H2O for diagnosis. Outcomes were
      VAP, ARDS, and death. RESULTS: Nine thousand one hundred twenty-six with blunt
      injury were ICU admissions, and 5,260 (58%) met study criteria (72% male). Means
      for age, ISS, and Glasgow Coma Scale score were 39, 12, and 14, respectively.
      There were 778 (15%) who received delayed Tx. Incidences of VAP, ARDS, and death
      were 5%, 1%, and 1%, respectively. Logistic regression analysis identified age,
      base excess, chest Abbreviated Injury Scale score, ISS, and any transfusion as
      significant predictors for VAP; chest Abbreviated Injury Scale score and
      transfusion as significant predictors for ARDS; and age and transfusion as
      significant predictors for death. CONCLUSION: Delayed transfusion is
      independently associated with VAP, ARDS, and death in trauma patients regardless
      of injury severity. These data mandate a judicious transfusion policy after
      resuscitation and emphasize the need for safe and effective blood substitutes and
      transfusion alternatives.

PMID- 16096533
TI  - Recombinant factor VIIa as adjunctive therapy for bleeding control in severely
      injured trauma patients: two parallel randomized, placebo-controlled, double
      blind clinical trials.
AB  - BACKGROUND: Uncontrolled bleeding is a leading cause of death in trauma. Two
      randomized, placebo-controlled, double-blind trials (one in blunt trauma and one
      in penetrating trauma) were conducted simultaneously to evaluate the efficacy and
      safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of
      bleeding in patients with severe blunt or penetrating trauma. METHODS: Severely
      bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 microg/kg)
      or placebo in addition to standard treatment. The first dose followed transfusion
      of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours
      later. The primary endpoint for bleeding control in patients alive at 48 hours
      was units of RBCs transfused within 48 hours of the first dose. RESULTS: Among
      301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma
      patients were eligible for analysis. In blunt trauma, RBC transfusion was
      significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6
      RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs)
      was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar
      analyses showed trends toward rFVIIa reducing RBC transfusion (estimated
      reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p =
      0.08). Trends toward a reduction in mortality and critical complications were
      observed. Adverse events including thromboembolic events were evenly distributed
      between treatment groups. CONCLUSION: Recombinant FVIIa resulted in a significant
      reduction in RBC transfusion in severe blunt trauma. Similar trends were observed
      in penetrating trauma. The safety of rFVIIa was established in these trauma
      populations within the investigated dose range.

PMID- 16096535
TI  - Hemostatic efficacy of two advanced dressings in an aortic hemorrhage model in
      Swine.
AB  - BACKGROUND: An effective hemostatic agent capable of stopping severe arterial
      bleeding and sustaining hemostasis over a prolonged time is required. The U.S.
      Army recently distributed fibrin sealant (under an Investigational New Drug
      approved protocol) and chitosan dressings among deployed medics for treating
      severe external hemorrhage on the battlefield. The purpose of this study was to
      evaluate the efficacy of these dressings, as compared with the standard gauze
      army field dressing, to provide initial and sustained hemostasis up to 96 hours
      in a lethal uncontrolled arterial hemorrhage model. METHODS: Anesthetized pigs
      were splenectomized and chronically instrumented for fluid/drug administration
      and continuous monitoring of vital signs. An infrarenal aortotomy was created
      using a 4.4-mm aortic hole punch and free bleeding was allowed for 5 seconds.
      While bleeding profusely, a dressing was applied and pressed into the wound for 4
      minutes (occluding the distal flow) and then released. If hemostasis was not
      obtained, the dressing was replaced with a new one (maximum, two dressings per
      experiment) with another 4-minute compression. If hemostasis was achieved, the
      abdomen was closed; the animal was then recovered and monitored up to 96 hours.
      Initial hemostasis, duration of hemostasis, survival time, blood loss, and other
      variables were measured. RESULTS: Application of army field dressing (gauze) did
      not stop the arterial hemorrhage and led to exsanguination of all the pigs (n =
      6) within 10 to 15 minutes of the injury. Chitosan dressing produced initial
      hemostasis in five of seven pigs. However, the dressings failed to maintain
      hemostasis for more than 1.6 hours (range, 28-102 minutes), resulting in
      secondary bleeding and death of the animals. Fibrin sealant dressing produced
      initial hemostasis in all the pigs (n = 6) and maintained hemostasis in five
      cases, with one failure at 2.2 hours. These pigs resumed normal activities and
      lived for the 96-hour experiment duration. Computed tomographic images and
      histologic sections of the aortas from surviving fibrin sealant dressing-treated
      animals showed formation of pseudoaneurysms and early granulation tissue at the
      aortotomy site. The posttreatment blood loss, duration of hemostasis, and
      survival time were significantly different in the fibrin sealant dressing group
      than the chitosan dressing and army field dressing groups. CONCLUSION: Both
      chitosan dressing and fibrin sealant dressing stopped initial arterial bleeding
      that could not be controlled by the standard army field dressing. However,
      although the fibrin sealant dressing secured hemostasis for up to 4 days, the
      chitosan dressing consistently failed within 2 hours after application. There may
      be a risk of rebleeding for high-pressure arterial wounds treated with chitosan
      dressings, particularly in situations where definitive care is delayed
      substantially.

PMID- 16096536
TI  - The role of transesophageal echocardiography in optimizing resuscitation in
      acutely injured patients.
AB  - BACKGROUND: The goal of resuscitation is to correct the mismatch between oxygen
      delivery and that of cellular demands. The pulmonary artery catheter (PAC) is
      frequently used to gauge the adequacy of resuscitation and guide therapy based on
      ventricular filling pressures. Transesophageal echocardiography (TEE) has emerged
      as a potential tool in assessing adequacy of acute hemodynamic resuscitation. The
      purpose of this study was to evaluate the role of TEE in assessing preload during
      ongoing volume resuscitation in trauma patients. METHODS: A retrospective review
      was conducted of acutely injured patients undergoing TEE during resuscitation
      from hemorrhagic shock from January 2002 to 2004 at a Level I trauma center. The
      indication for TEE was persistent hemodynamic instability in the absence of
      ongoing surgical hemorrhage. Variables included hemodynamic and PAC parameters,
      pre-TEE resuscitation volume, and vasopressor requirements. The impact of TEE
      findings on therapeutic decisions was evaluated. RESULTS: Twenty-five patients
      underwent TEE, 18 (72%) had an indwelling PAC with a mean pulmonary artery
      occlusion pressure of 19.3 mm Hg (range, 12-29 mm Hg) and mean cardiac index of
      2.9 L/min/m2 (range, 1.6-4.6 L/min/m2). Twelve patients (48%) were receiving
      inotropes and/or vasopressors for hypotension at the time of TEE. Resuscitation
      volume within 6 hours before TEE included a mean of 6.5 L of crystalloid and 12.2
      units of blood products (packed red blood cells, fresh frozen plasma, and
      platelets). TEE revealed left ventricular hypovolemia in 13 patients (52%) and
      altered therapy in 16 patients (64%), including additional volume (n = 13),
      addition of an inotrope (n = 4), and addition of a vasodilator (n = 1) in one
      patient with ventricular overdistention. Comparison of the abnormal and normal
      TEE groups revealed that only cardiac index was significantly different (2.6
      L/min/m2 in the abnormal group vs. 3.9 L/min/m2 in the normal group; p = 0.005).
      Significant mitral valve regurgitation leading to valve replacement was
      identified in one patient. No clinically relevant pericardial effusion was
      identified. CONCLUSION: TEE altered resuscitation management in almost two thirds
      of patients. Many patients with "acceptable" pulmonary artery occlusion pressure
      parameters may in fact have inadequate left ventricular filling. In addition, TEE
      offers the advantage of direct assessment of cardiac valve competency, myocardial
      wall contractility, and pericardial fluid.

PMID- 16096537
TI  - Trauma base knowledge and the effect of the trauma evaluation and management
      program among senior medical students in seven countries.
AB  - BACKGROUND: We compared base trauma knowledge and the impact of the Trauma
      Evaluation and Management (TEAM) program among senior medical students in seven
      countries. METHODS: We compared pre- and post-TEAM multiple choice question
      scores of fourth-year students in Jamaica (n = 32), Trinidad (n = 32), Costa Rica
      (n = 64), Australia (n = 35), United Arab Emirates (n = 68), Toronto (n = 29) and
      Pennsylvania (n = 34). Means and degree of improvement were compared by analysis
      of variance (p < 0.05 for statistical significance). Percentage pass (based on
      70% or 60% pass mark), student's perception of instruction level, and grading of
      TEAM (based on the percentage of students grading 1-5 for each category) were
      assessed by chi2 analysis. [table: see text]. RESULTS: Only 31.4% of students
      achieved the borderline pass mark of 60%, and 5.4% achieved a clear pass mark of
      70%. The performance before and after TEAM was quite variable among medical
      schools. A grade of > or = 4 was assigned by 74% to 100% for objectives,
      knowledge improvement, satisfaction, and recommending TEAM for the curriculum.
      TEAM was rated "just right" by 70.3% to 92.7%, "too simple" by 1.6% to 21.6%, and
      "too advanced" by 3.3% to 13.5% of students. CONCLUSION: Base trauma knowledge in
      these students, though variable, was generally very low and improved with TEAM.
      Our data suggest a need for greater undergraduate emphasis in trauma education.

PMID- 16096538
TI  - Relationship between pseudoaneurysm formation and biloma after successful
      transarterial embolization for severe hepatic injury: permanent embolization
      using stainless steel coils prevents pseudoaneurysm formation.
AB  - OBJECTIVE: The purpose of this study was to determine the association between
      bilomas and pseudoaneurysm complications after severe hepatic injury. METHODS:
      Angiography was performed in patients with American Association for the Surgery
      of Trauma grade > or = III hepatic injury on contrast-enhanced computed
      tomographic scanning. When contrast extravasation was observed, transarterial
      embolization (TAE) was performed. After TAE, technetium-99m pyridoxyl-5-methyl
      tryptophan cholescintigraphy was performed to detect the coexistence of bilomas.
      Follow-up angiography was performed when a biloma was detected. Eighty
      consecutive patients underwent angiography; after angiography, five patients
      died. The remaining 75 patients who underwent cholescintigraphy were included in
      this study. RESULTS: All 11 patients who had bilomas had angiographic evidence of
      contrast extravasation. The biloma frequency was higher in patients with grades
      IV and V injuries than in those with grade III injury (p = 0.024). Follow-up
      angiography revealed pseudoaneurysms in 7 of these 11 patients. All six patients
      in whom only gelatin sponge pledget injection was used to embolize had
      pseudoaneurysms. Among them, two patients had computed tomographic evidence of
      massive intra-abdominal fluid collection. In contrast, only one of five patients
      who received the combination of gelatin sponge pledget injection and stainless
      steel coils to permanently embolize injured arteries had a pseudoaneurysm. In
      this patient, the pseudoaneurysm was found in the peripheral part of the
      collateral vessels. All patients with pseudoaneurysms underwent repeat TAE and
      were discharged from the hospital uneventfully. CONCLUSION: In patients with high
      grade hepatic injury and arterial bleeding who developed biloma, use of a gelatin
      sponge, an absorbable embolic material, is associated with a risk of
      pseudoaneurysm formation. Permanent arterial embolization using stainless steel
      coils is indicated to decrease this risk.

PMID- 16096539
TI  - Store-operated calcium channel inhibition attenuates neutrophil function and
      postshock acute lung injury.
AB  - BACKGROUND: A wide variety of neutrophil (PMN) functions are regulated by
      cytosolic calcium concentration. Calcium channel blockade might therefore
      decrease postshock inflammation but could also limit important cardiovascular
      compensations. PMN Ca2+ entry occurs, however, through store-operated calcium
      entry (SOCE) channels rather than the voltage operated (L-type) channels that
      regulate cardiovascular tone. We hypothesized that SOCE inhibition might suppress
      postshock PMN activation, lessening lung injury without compromising
      cardiovascular performance. METHODS: Human PMNs were treated in vitro with N
      propargyl-nitrendipine (MRS1845 [MRS]) a dihydropyridine Ca2+ channel blocker
      with relative specificity for SOCE channels. Calcium flux was measured by fura
      fluorescence. Chemotaxis was studied in modified Boyden chambers. Respiratory
      burst was studied by dihydrorhodamine fluorescence. Exploratory studies were then
      performed where rats were subjected to trauma and hemorrhagic shock (T/HS)
      (laparotomy, then hemorrhage to a mean arterial pressure of 30-40 mm Hg for 90
      minutes) after pretreatment with MRS or vehicle given intraperitoneally at
      laparotomy. In vivo PMN CD11b expression was then assayed by flow cytometry and
      lung injury was assessed as percentage Evans blue dye leak 3 hours after
      resuscitation. The shed blood volume required to achieve standardized hypotension
      was measured. RESULTS: In vitro, MRS suppressed human PMN SOCE without affecting
      calcium store release; it suppressed chemotaxis (60 +/- 6 vs. 150 +/- 15 x 10(3)
      PMNs/well, p = 0.002) and suppressed respiratory burst (62 +/- 11% vs. 100%, p <
      0.05) at IC50 concentrations similar to those needed to suppress SOCE. In
      subsequent in vivo rat studies, MRS decreased postshock PMN CD11b expression from
      397 +/- 93 to 268 +/- 39 MFU mean flourescent units (p < 0.05) and decreased lung
      Evans blue dye permeability from 8.1 +/- 1.9% to 3.4 +/- 0.1% (p < 0.05). MRS had
      no noticeable effect on the relationship between blood pressure and blood loss,
      with shed blood volume remaining almost identical (26 +/- 2 mL/kg vs. 27 +/- 3
      mL/kg, p = not significant). CONCLUSION: Modulation of PMN Ca2+ entry by means of
      selective SOCE channel inhibition attenuates PMN inflammatory responses in vitro.
      In vivo, SOCE channel blockade attenuates trauma and hemorrhagic shock-induced
      PMN priming and lung injury without gross evidence of hemodynamic side effects.
      The relative specificity of SOCE channel blockade for "nonexcitable" cells such
      as PMNs may make it a valuable form of chemoprophylaxis for the inflammatory
      consequences of hemorrhagic shock in trauma patients.

PMID- 16096540
TI  - Smoke inhalation enhances early alveolar leukocyte responsiveness to endotoxin.
AB  - BACKGROUND: Pulmonary dysfunction after smoke inhalation and thermal injury is
      associated with excessive morbidity and mortality. The purpose of this study was
      to evaluate alveolar leukocyte function after thermal injury and smoke
      inhalation. METHODS: Twenty-one patients with thermal injury only (n = 8);
      thermal injury and smoke inhalation injury (n = 8); and nonburned controls (n =
      5) were assessed by means of bronchoscopically directed lavage (bronchoalveolar
      lavage [BAL]) on the first and fourth days postinjury. BAL-isolated pulmonary
      leukocytes were assessed for number, composition, viability, and production of
      tumor necrosis factor (TNF)alpha, interleukin (IL)-8, and IL-6 in response to 100
      ng/mL of lipopolysaccharide (LPS) (mean +/- SEM; significance at p < 0.05).
      RESULTS: Six of eight Smoke patients had gross evidence of lung injury. On day 1,
      Smoke and Burn BAL isolates yielded greater cell counts than Control (10.6 vs.
      4.5 vs. 2.4 x 10(6)/mL). Smoke macrophages on day 1 produced more TNFalpha (1.2
      vs. 0.2 ng/mL), IL-6 (8.0 vs. 1.9 ng/mL), and IL-8 (85 vs. 32 ng/mL) after LPS
      stimulation compared with respective unstimulated (0 ng/mL of LPS) day-1 Smoke
      cells. LPS-stimulated Burn cells on day 1 produced more IL-8 (150 vs. 62 ng/mL)
      but not TNFalpha (0.4 vs. 0.25 ng/mL) or IL-6 (1.8 vs. 0.69 ng/mL), when compared
      with respective unstimulated Burn cells. By day 4, LPS-stimulated Smoke and Burn
      cells produced significantly more TNFalpha (Smoke, 0.41 vs. 0.16 ng/mL; Burn,
      0.87 vs. 0.51 ng/mL) and IL-6 (Smoke, 2.5 vs. 0.47 ng/mL; Burn, 4.1 vs. 1.47
      ng/mL), but not IL-8 (Smoke, 51.1 vs. 51.1 ng/mL; Burn, 54.4 vs. 55.6 ng/mL),
      compared with respective unstimulated day-4 cells. CONCLUSION: Smoke inhalation
      induces a massive influx of alveolar leukocytes that are primed for an early,
      enhanced LPS-activated cytokine response compared with alveolar leukocytes
      isolated after burn injury alone or normal controls.

PMID- 16096541
TI  - Preliminary experience with airway pressure release ventilation in a
      trauma/surgical intensive care unit.
AB  - BACKGROUND: Airway pressure-release ventilation (APRV) is a pressure-limited,
      time-cycled mode of mechanical ventilation. The purpose of this study was to
      evaluate our initial experience with the use of APRV in acutely injured,
      ventilated patients. METHODS: Since March 2003, APRV has been used selectively in
      adult trauma patients with or at risk for acute lung injury/acute respiratory
      distress syndrome. Data were obtained before and during the 72 hours after
      switching to APRV. A retrospective analysis of these data was then performed.
      RESULTS: Complete data were available on 46 of 60 patients (77%) for the first 72
      hours of APRV. Before APRV, the average Pao2/Fio2 ratio was 243 and the average
      peak airway pressure was 28 cm H2O. Peak airway pressure decreased 19% (p =
      0.001), Pao2/Fio2 improved by 23% (p = 0.017) and release tidal volumes improved
      by 13% (p = 0.020) over the course of the analysis. CONCLUSION: APRV
      significantly improved oxygenation by alveolar recruitment and allowed for a
      reduction in peak airway pressures. This relatively new modality had favorable
      results and appears to be an effective alternative for lung recruitment in
      traumatically injured patients at risk for acute lung injury/acute respiratory
      distress syndrome.

PMID- 16096542
TI  - The position of the Eastern Association for the Surgery of Trauma on the future
      of trauma surgery.

PMID- 16096543
TI  - Admission hyperglycemia is predictive of outcome in critically ill trauma
      patients.
AB  - OBJECTIVES: There is a paucity of data evaluating whether hyperglycemia at
      admission is associated with adverse outcome in trauma patients. Our objectives
      were to determine whether admission hyperglycemia was predictive of outcome in
      critically ill trauma patients. METHODS: Prospective data were collected daily on
      1,003 consecutive trauma patients admitted to the intensive care unit over a 2
      year period. Diabetics were excluded. Patients were stratified by admission serum
      glucose level (<200 mg/dL vs. > or =200 mg/dL) age, gender, Injury Severity
      Score, and other preexisting risk factors. Outcome was measured by incidence of
      infection, ventilator days, hospital length of stay and intensive care unit
      length of stay, and mortality. Multiple linear regression models were used to
      determine level of significance. RESULTS: Two hundred fifty-five of 1,003 (25%)
      patients were admitted with hyperglycemia over the study period. The majority
      (78%) of the admissions were caused by blunt injury. Male patients accounted for
      the majority of the study population (73%); however, female patients were more
      likely to be hyperglycemic at admission (p = 0.015). Patients with hyperglycemia
      had an overall greater infection rate and hospital length of stay. The
      hyperglycemic group had a 2.2-times greater risk of mortality when adjusted for
      age and Injury Severity Score. CONCLUSION: Hyperglycemia at admission is an
      independent predictor of outcome and infection in trauma patients. Future
      investigation on the effects of hyperglycemia are warranted.

PMID- 16096544
TI  - Intubation of pediatric trauma patients in the field: predictor of negative
      outcome despite risk stratification.
AB  - BACKGROUND: Recently, evidence has shown that intubation in the field may not
      improve or may even adversely affect outcomes. Our objective was to analyze
      outcomes in pediatric intubated trauma patients using a large national pediatric
      trauma registry. METHODS: The patient population was derived from the last phase
      of the National Pediatric Trauma Registry, comprising admissions from 1994
      through 2002. Intubated patients were identified, as was their place of
      intubation: in the field, at a hospital that was not a trauma center, and at a
      trauma center. Risk stratification was performed for mortality using logistic
      regression models and variables available at presentation to the emergency room.
      Odds ratio and variable significance were calculated from the logistic regression
      model. The percentage of patients discharged to home and an abnormal Functional
      Independence Measure at hospital discharge examined functional outcome of
      survivors. RESULTS: There were a total of 50,199 patients, 5460 (11.6%) of whom
      were intubated (1,930 in the field, 1,654 in the hospital, and 1,876 in a trauma
      center). Unadjusted mortality rates for intubated patients were as follows:
      field, 38.5%; hospital, 16.7%; and trauma center, 13.2% (all different, p <
      0.05). The developed logistic regression model had an area under the receiver
      operating characteristic curve of 0.98. Compared with nonintubated patients, the
      odds ratio for field intubation, for non-trauma center, and for trauma center
      intubation was 14.4, 5.8, and 4.8, respectively (significantly different field
      vs. either hospital). The actual (observed) death rate was significantly higher
      than predicted in those intubated in the field. Stratification of injury by New
      Injury Severity Score or degree of head injury showed that this difference
      extended from mild to severe (e.g., odds ratio for New Injury Severity Score < 15
      field vs. trauma center intubation, 12.3; odds ratio for none or moderate head
      injury, 5.1). Similar results were obtained for functional outcome in the
      survivors. CONCLUSION: Field intubation is an independent strong negative
      predictor of survival or good functional outcome despite adjustment for severity
      of injury. Although not causal, the magnitude of these differences should lead to
      future controlled studies of pediatric trauma field intubations.

PMID- 16096545
TI  - How long should you wait for a chest radiograph after placing a chest tube on
      water seal? A prospective study.
AB  - OBJECTIVE: The purpose of this study was to determine the optimal time interval
      for identifying a pneumothorax (PTX) on chest radiograph (CXR) after placing a
      chest tube on water seal. METHODS: One hundred nineteen chest tubes were placed
      on water seal according to a prospective, observational study protocol. After
      water seal, both an early (3.1 +/- 2.1 hours) and a late (17.6 +/- 8.0 hours) CXR
      was obtained. RESULTS: Thirty-one patients had a PTX on follow-up CXRs. There
      were 22 early and 9 late PTXs identified. Three patients in the early group had a
      clinically significant PTX or an increase in the size of PTX on follow-up CXR.
      None of the patients in the late group had a clinically significant PTX (any
      worsening of their PTX) or required further intervention. CONCLUSION: A normal
      chest radiograph obtained 3 hours after placing a chest tube on water seal
      effectively excludes development of a clinically significant pneumothorax.

PMID- 16096546
TI  - Prehospital chest tube thoracostomy: effective treatment or additional trauma?
AB  - BACKGROUND: The use of prehospital chest tube thoracostomy (TT) remains
      controversial because of presumed increased complication risks. This study
      analyzed infectious complication rates for physician-performed prehospital and
      emergency department (ED) TT. METHODS: Over a 40-month period, all consecutive
      trauma patients with TT performed by the flight physician at the accident scene
      were compared with all patients with TT performed in the emergency department.
      Bacterial cultures, blood samples, and thoracic radiographs were reviewed for TT
      related infections. RESULTS: Twenty-two patients received prehospital TTs and 101
      patients received ED TTs. Infected hemithoraces related to TTs were found in 9%
      of those performed in the prehospital setting and 12% of ED-performed TTs (not
      significant). CONCLUSION: The prehospital chest tube thoracostomy is a safe and
      lifesaving intervention, providing added value to prehospital trauma care when
      performed by a qualified physician. The infection rate for prehospital TT does
      not differ from ED TT.

PMID- 16096547
TI  - The evolving role of interventional radiology in trauma care.
AB  - BACKGROUND: Although the traditional role of radiology in trauma care has been
      diagnostic, therapeutic interventional radiology (IR) techniques have now become
      essential in the management of many injuries. We hypothesized that IR has evolved
      at our institution over the last decade from a largely diagnostic to a more
      therapeutic role in the care of the injured patient. METHODS: Demographic
      information, computed tomographic scans of the chest and abdomen, and
      angiographic procedures (APs) performed within 48 hours of admission were
      reviewed in all patients evaluated at a Level I trauma center for the periods
      1993 to 1995 and 2000 to 2002. All APs performed with the intent to embolize,
      stent, or insert a device into a vessel were designated as therapeutic. Analysis
      by means of chi provided between-group comparisons for questions of interest and
      the Student's t test was used for comparison of means. RESULTS: A total of 4,750
      patients were reviewed, 1,677 from the time period 1993 to 1995 and 3,073 from
      the period 2000 to 2002. Overall injury severity as measured by the Injury
      Severity Score (ISS) was similar in both groups (9.6 vs. 9.9, p = not
      significant). The number of angiograms obtained decreased significantly from 7.1%
      to 4.0% of all patients (p < 0.01). Concurrently, the fraction of all angiograms
      that were considered therapeutic rose from 10% to 22% (p < 0.05). The overall
      number of aortic arch angiograms decreased over time (from 3.6% to 0.9%, p <
      0.01), and the percentage of positive examinations increased from 5.0% to 21.4%.
      In comparison, the number of computed tomographic scans of the chest increased
      from 1.6% of all patients to 10.8% (p < 0.01). CONCLUSION: Axial imaging studies
      are being used more frequently to screen trauma patients for injury.
      Concurrently, diagnostic APs are less frequently performed but are more
      frequently positive. In addition, IR studies are increasingly focused on
      therapeutic intervention. IR program development and support is an integral
      aspect of modern trauma care. These findings have prompted our institution to
      equip the IR suite to function as an active resuscitation area similar to the
      trauma bay and intensive care unit.

PMID- 16096548
TI  - Human immunodeficiency virus, hepatitis B, and hepatitis C seroprevalence in a
      Canadian trauma population.
AB  - BACKGROUND: The current seroprevalence of human immunodeficiency virus (HIV),
      hepatitis B, and hepatitis C in the Canadian trauma population is unknown.
      Establishing the seroprevalence of these diseases is vital for education,
      postexposure prophylaxis, and counseling, and to establish potential screening
      guidelines. The purpose of this study was to determine the seroprevalence of HIV,
      hepatitis B, and hepatitis C in the trauma population of London, Ontario, Canada.
      METHODS: All adult (aged > or = 18 years) trauma patients treated by the trauma
      team at London Health Sciences Centre were prospectively studied from January to
      December 2003. The study was conducted as a linked, confidential serosurvey with
      delayed full disclosure. Serum was analyzed for HIV, hepatitis C antibody, and
      Hepatitis B surface antigen. RESULTS: A total of 287 (76%) of 377 consecutive
      trauma patients had blood testing completed. Of the 287 patients tested, 1 (0.3%)
      was positive for hepatitis B, 8 (2.8%) were positive for hepatitis C, and no
      patients tested positive for HIV. Hepatitis C-positive patients were
      predominantly men (63%) with a mean age of 46 years and a mean Injury Severity
      Score of 19; 63% were injured in a motor vehicle crash, and 88% were discharged
      alive. There were no statistically significant differences in the demographic and
      injury profiles from the hepatitis C-negative patients (p > 0.2 for all).
      CONCLUSION: This is the first study to determine the rates of HIV, hepatitis B,
      and hepatitis C in the Canadian trauma population. Our trauma population
      demonstrated a threefold higher hepatitis C seroprevalence rate compared with the
      general population. Hepatitis C poses the highest risk to the trauma team of the
      three bloodborne diseases studied. With no vaccine or postexposure prophylaxis
      currently available for hepatitis C, this study highlights the importance of
      prevention and the strict use of universal precautions in the setting of trauma.

PMID- 16096549
TI  - Visual outcome after fireworks injuries.
AB  - BACKGROUND: The epidemiology and prognosis of fireworks-related injuries treated
      at a tertiary eye care center in less developed nations remain unknown. METHODS:
      We conducted a prospective observational study that enrolled all consecutive eyes
      with fireworks-related ocular injury visiting our trauma clinic during a 1-year
      period. Eyes were graded by ocular trauma classification and followed for 6
      months at least. Best corrected visual acuity (BCVA) at 6 months was considered
      the final visual outcome. Data were analyzed. RESULTS: Twenty-five (96%) of a
      total of 26 patients enrolled during study period were male patients and 13 (50%)
      were younger than 15 years. The type of fireworks involved was a bottle rocket in
      38.5%. Factors significantly associated with better final visual outcome were
      better BCVA at presentation (p = 0.041), absence of bottle rocket injury (p =
      0.028), closed globe injury (p = 0.028), absence of relative afferent pupillary
      defect (p = 0.019), absence of intraocular foreign body (p = 0.026), and absence
      of endophthalmitis (p = 0.006). Besides poor visual outcome, bottle rocket
      injuries were more frequently associated with facial lacerations, intraocular
      foreign body, and endophthalmitis development. CONCLUSION: Fireworks-related
      ocular injuries commonly affect young male subjects of northern India. Visual
      outcome is better in eyes having better initial BCVA or closed globe injury and
      if relative afferent pupillary defect, bottle rocket injury, intraocular foreign
      body, and endophthalmitis are absent.

PMID- 16096550
TI  - Major trauma in pregnant women during the summer.
AB  - BACKGROUND: Pregnant women represent a major challenge in trauma care because of
      the risks to both mother and child and because of the difficulties in following
      standard protocols. METHODS: We analyzed data for all pregnant women admitted to
      the hospital in Canada over 7 years to test whether major trauma still clustered
      in the summer despite their aversion toward alcohol, recklessness, and extreme
      sports. RESULTS: A total of 2,618 pregnant women sustained major trauma. The
      prevalence of pregnancy was marginally lower in summer than in winter (decrease,
      3%; 95% confidence interval, 2-4%), whereas the incidence of major trauma in
      pregnant women was significantly higher in summer than in winter (increase, 12%;
      95% confidence interval, 3-21%; p = 0.005). No evidence of offsetting decreases
      in severity appeared in analyses of length of stay, number of surgical
      procedures, or mortality. CONCLUSION: We suggest that normal lifestyle choices
      contribute to an increased risk of major trauma during pregnancy and merit
      greater awareness throughout the year.

PMID- 16096551
TI  - Spine and spinal cord injury in motor vehicle crashes: a function of change in
      velocity and energy dissipation on impact with respect to the direction of crash.
AB  - OBJECTIVE: To examine the effect of change in velocity (DeltaV) and energy
      dissipation (IE) on impact, above and below the test levels for Federal MVC
      Safety Standards, on the incidence of spine fractures (SF), spinal cord injury
      (SCI)), SF mortality and the associated injury patterns in Frontal (F) and
      Lateral (L) MVCs. Comparison of 214 patients with SF or SCI with 938 patients who
      did not have SF or SCI. METHODS: 1152 MVC adult drivers or front-seat passengers
      (701 F & 451 L) evaluated at 10 Level I CIREN study Trauma Centers together with
      vehicle and crash scene engineering reconstruction. Patient seat belt (SB) and/or
      airbag (AB) use correlated with clinical, or autopsy findings. RESULTS: The
      relationship between DeltaV and IE rose exponentially as DeltaV increased. Of the
      1152 patients, all with AIS> or =3 injuries, there were 214 patients with spine
      fractures of AIS > or =2. In FMVCs there were more SF patients with Cervical SF
      than in LMVCs (68F versus 64 L) and more Thoracic (35F versus 21L) and Lumbar
      (39F versus 16L) SF. However, the incidence of spinal cord injury was greatest in
      the Cervical SF (33%), compared with the Thoracic SF (18%), or Lumbar SF (2%).
      Most important, in FMVCs 49% of SF, 47% of SCI and 71% of the SF deaths (p <
      0.05) occurred at > mean of 47.4 kph. In contrast, in LMVCs 51% of SF, 52% of SCI
      and 67% of the SF deaths occurred at DeltaV > mean of 35.3 kph. However, 80% of
      all deaths in SCI occurred in Cervical SF cases, in these 74% also had a brain
      injury. In contrast, the deaths in Thoracic SF were due to combinations of brain
      (45%), thorax (95%) or associated pelvic fracture injuries (50%). Airbag (AB), or
      Seat belt (SB) restraints appeared to protect FMVC SF patients from SCI at lower
      DeltaV, but 84% of Cervical SCI patients at DeltaV > 47 kph had AB protection and
      in a few cases the AB appeared responsible for the SCI. In contrast, 82% of
      Lumbar SF patients had SB, but in FMVCs where jackknifing due to backloading
      occurred, improper SB positioning may have contributed to the SF. CONCLUSIONS:
      The implication for SCI in both front seat drivers and passengers in either FMVC
      or LMVC crashes above their respective DeltaV means is that improved spine
      fracture protection is necessary at higher DeltaV levels. More effective safety
      systems to prevent Cervical SCIs should be developed using two-level frontal and
      side AB & SB+pretensioner devices, which protect against SF at DeltaV both at and
      1SD above the FMVC (47 & 72 kph = 30 & 45 mph) and LMVC (35 & 54 kph =22 & 34
      mph) means.

PMID- 16096552
TI  - Predicting significant torso trauma.
AB  - BACKGROUND: Identification of motor vehicle crash (MVC) characteristics
      associated with thoracoabdominal injury would advance the development of
      automatic crash notification systems (ACNS) by improving triage and response
      times. Our objective was to determine the relationships between MVC
      characteristics and thoracoabdominal trauma to develop a torso injury probability
      model. METHODS: Drivers involved in crashes from 1993 to 2001 within the National
      Automotive Sampling System were reviewed. Relationships between torso injury and
      MVC characteristics were assessed using multivariate logistic regression.
      Receiver operating characteristic curves were used to compare the model to
      current ACNS models. RESULTS: There were a total of 56,466 drivers. Age,
      ejection, braking, avoidance, velocity, restraints, passenger-side impact,
      rollover, and vehicle weight and type were associated with injury (p < 0.05). The
      area under the receiver operating characteristic curve (83.9) was significantly
      greater than current ACNS models. CONCLUSION: We have developed a
      thoracoabdominal injury probability model that may improve patient triage when
      used with ACNS.

PMID- 16096553
TI  - The cardiac pendulum: blunt rupture of the pericardium with strangulation of the
      heart.
AB  - BACKGROUND: Blunt injury of the pericardium with strangulation of the heart is a
      rare clinical injury. METHODS: We conducted a review of clinical records and
      performed prospective collection of forensic data from a large urban medical
      examiner's office. RESULTS: Ten cases of blunt injury to the pericardium were
      identified. All were secondary to blunt trauma. Nine of the 10 cases had
      associated chest wall injuries and 5 of the 10 cases had cardiac strangulation.
      CONCLUSION: Pericardial lacerations are common findings at autopsy. Clinically,
      those that survive to the hospital have a confusing presentation. They are often
      diagnosed during emergent thoracotomy for hemodynamic instability. Hemodynamic
      deterioration associated with change in patient position may be a clue to cardiac
      strangulation.

PMID- 16096554
TI  - A salmon thrombin-fibrin bandage controls arterial bleeding in a swine aortotomy
      model.
AB  - BACKGROUND: Recently, a wide variety of bandages have been formulated to attempt
      to improve the effectiveness of emergency intervention in situations of
      uncontrolled bleeding. The best of these dressings contain a mixture of human
      thrombin and fibrinogen. The presence of human components in these bandages,
      although effective, increases the cost of the dressing and raises questions of
      availability of raw materials and transmission of pathogens. The purpose of this
      study was to investigate the efficacy of dressings composed of salmon thrombin
      and fibrinogen in a swine aortotomy model. METHODS: A 4.4-mm aortotomy was
      produced in the abdominal aorta of 19 anesthetized, splenectomized swine. The
      United States Army standard field gauze was applied to 8 animals, and the salmon
      thrombin-fibrin dressing (SFD) was applied to 11 animals. Survival, blood loss,
      and other parameters were measured over a 60-minute period. RESULTS: All 11
      animals that received the SFD survived the aortotomy injury, and bleeding stopped
      within 7.5 +/- 1.5 min. Seven of 8 animals in the control group were killed when
      bleeding continued and blood pressures decreased to the cutoff values as outlined
      in the animal protocol. Bleeding was significantly less in the SFD group compared
      with the gauze group (241 +/- 65.3 vs. 932.7 +/- 142.4 mL). CONCLUSION: Fibrin
      dressing using salmon-derived thrombin and fibrinogen is effective in controlling
      severe, uncontrolled bleeding. This dressing may offer an alternative to
      dressings composed of human coagulation proteins.

PMID- 16096555
TI  - "Low-dose" recombinant activated factor VII results in less blood and blood
      product use in traumatic hemorrhage.
AB  - BACKGROUND: This study was designed to compare mortality and blood product use in
      patients who received recombinant activated factor VII (rFVIIa) for traumatic
      hemorrhage to a matched historic control. METHODS: Trauma registry data of
      bleeding trauma patients who received rFVIIa (40 microg/kg, repeated once if
      needed) included 28-day mortality; pre- and post-rFVIIa international normalized
      ratio; and packed red blood cell (PRBC), fresh frozen plasma, platelet, and
      cryoprecipitate requirements. A control group was created of bleeding patients
      who did not receive rFVIIa by matching for Injury Severity Score and age. The
      chi2 and Student's t tests were used to test for significance. RESULTS: Twenty
      nine patients, well matched to 72 control patients, made up the rFVIIa group.
      rFVIIa corrected international normalized ratio within 4 hours (from 4.4 to 1.2;
      p < 0.0001). There was no difference in mortality (control, 40.3%; rFVIIa,
      41.4%). The rFVIIa group required significantly fewer PRBC transfusions than the
      control group (18.3 +/- 7.5 vs. 22.0 +/- 9.7; p = 0.036). Compared with the
      control group, the rFVIIa group required fewer platelet transfusions (1.4 +/- 1.2
      vs. 2.3 +/- 2.1; p = 0.01) and less cryoprecipitate (0.59 +/- 0.54 vs. 1.5 +/-
      1.8; p = 0.006). CONCLUSION: rFVIIa resulted in significantly less PRBC,
      platelet, and cryoprecipitate use and equivalent mortality when compared with the
      matched control group, with no increase in complications.

PMID- 16096556
TI  - Effect of recombinant FVIIa in hypothermic, coagulopathic pigs with liver
      injuries.
AB  - BACKGROUND: Previous experiments with diverse pig models to evaluate the ability
      of rFVIIa to reduce hemorrhage have provided divergent results. The current study
      was conducted to address concerns related to previous work by using larger sample
      sizes, and an extended observational period of 4 hours post-injury. The
      objectives were to evaluate further the hemostatic efficacy and safety of rFVIIa
      administration after traumatic, uncontrolled hemorrhage. METHODS: Anesthetized,
      splenectomized pigs (36.6 +/- 0.3 kg; n = 18/group) underwent an approximately
      50% isovolemic blood exchange with 33 degrees C 6% hetastarch, and body
      temperature was adjusted to 32.5 +/- 0.5 degrees C. Subsequently, a Grade V liver
      injury was inflicted. After 30 seconds, either vehicle or treatment (180
      microg/kg or 720 microg/kg rFVIIa) was administered intravenously as a bolus.
      Concomitantly, laparotomy pads were packed around the liver. Resuscitation with
      33 degrees C lactated Ringer's solution (260 mL/min) was initiated and pigs were
      monitored for 4 hour post-injury or until death. Tissues were collected and
      examined histologically to assess the presence of disseminated intravascular
      coagulation (DIC). RESULTS: Liver injuries were comparable among all groups (p =
      0.89). Measures associated with in vitro coagulation (prothrombin time, activated
      partial thromboplastin time, thromboelastographic split-point and R times) were
      enhanced by rFVIIa administration (p < 0.05). However, neither percent survival
      (p = 0.82), survival time (p = 0.56), nor blood loss (p = 0.63) were affected by
      treatment. DIC was not evident in lung or kidney tissue. CONCLUSIONS: These data
      indicate an inability of rFVIIa at these doses to reduce blood loss, or to
      increase survival time or percent survival in this pig model. Absence of DIC
      provides evidence for safe use of rFVIIa under conditions specific to this study.

PMID- 16096557
TI  - L-arginine improves wound healing after trauma-hemorrhage by increasing collagen
      synthesis.
AB  - BACKGROUND: Several studies indicate impaired wound healing after trauma and
      shock. Wound immune cell dysfunction seems to be responsible for altered wound
      healing after trauma-hemorrhage (T-H). In this respect, administration of the
      amino acid L-arginine normalized wound immune cell function under those
      conditions. It remains unknown, however, whether L-arginine improves impaired
      wound healing after T-H. METHODS: To study this, male C3H/HeN mice were subjected
      to a midline laparotomy (i.e., soft tissue trauma induced), and polyvinyl sponges
      were implanted subcutaneously at the wound site before hemorrhage (35 +/- 5 mm Hg
      for 90 minutes) or were subjected to sham operation. During resuscitation, mice
      received 300 mg/kg body weight L-arginine or saline (vehicle). Seven days
      thereafter, hydroxyproline (OHP), a metabolite of collagen synthesis, was
      measured in the wound fluid using high-performance liquid chromatography.
      Collagen types I and III were determined in the wound by Western blot analysis.
      In addition, wound breaking strength was measured 10 days after T-H or sham
      operation. RESULTS: The results indicate that OHP was significantly decreased in
      T-H mice. L-arginine, however, restored depressed OHP in the wound fluid in the T
      H animals. Similarly, L-arginine treatment prevented a significant depression of
      collagen I synthesis after T-H. Collagen III was not significantly affected by T
      H or L-arginine. Most important, L-arginine increased maximal wound breaking
      strength after severe blood loss. Therefore, L-arginine improves wound healing
      after T-H by increasing collagen synthesis. CONCLUSION: Because L-arginine
      improves wound healing, the results suggest that L-arginine might represent a
      novel and useful adjunct to fluid resuscitation for decreasing wound
      complications after trauma and severe blood loss.

PMID- 16096558
TI  - Spectrum of ocular injuries in children with major trauma.
AB  - BACKGROUND: Few studies document the variety of ocular injuries encountered in
      children after major trauma. This study was performed to determine the type and
      frequency of ocular injuries in a large population of children with major trauma.
      METHODS: All children with ocular and adnexal injuries (n = 7497) among 96,879
      children registered in the National Pediatric Trauma Registry (NPTR) were
      analyzed. Children were stratified for Injury Severity Score (ISS is a method for
      categorizing patients with multiple injuries in which an ISS > 15 is considered
      major trauma), age, sex, injury, protective restraint, vision threatening injury,
      and basilar skull fracture. RESULTS: Nearly 8% of the children in the NPTR
      sustained an ocular injury. These children had one or more injuries to one or
      both eyes and/or the ocular adnexa for an average of 1.3 ocular injuries per
      child. Three-fourths (75%) of the children with an ocular injury had an ISS < or
      = 15 and one-fourth (25%) had an ISS > 15. Among children with an ISS > 15 the
      most common injuries were orbital wall fracture (59%) and contusion of the eye
      and ocular adnexa (18%). Among these same children with an ISS > 15, the percent
      of orbital wall fractures, injuries to the optic nerve, and injuries to the other
      ocular cranial nerves doubled while the percent of basilar skull fractures
      tripled when compared with children with an ISS < or = 15. Penetrating injuries
      of the globe were significantly lower in children with an ISS > 15 than in
      children with an ISS < or = 15. Over 70% of the children with an eye injury and
      an ISS > 15 sustained injury in an accident involving a motorized or non
      motorized vehicle, and over 75% of those who could have been restrained, were not
      restrained. CONCLUSIONS: Children with an ocular injury sustained during major
      trauma (ISS > 15) are more likely to have a basilar skull fracture, orbital wall
      fracture, and a contusion of the eye and/or the ocular adnexa as compared with
      children with ISS < or = 15. Children with any of these injuries sustained during
      major trauma should be afforded prompt ophthalmologic evaluation to uncover
      injury to components of the visual system.

PMID- 16096559
TI  - Gender differences in etiology and outcome of open globe injuries.
AB  - PURPOSE: Patterns of injury and outcomes after multi-system trauma differ between
      men and women. Few data exist regarding the epidemiology of gender differences in
      severe eye trauma. We hypothesized that the incidence and patterns of open globe
      injuries might differ between men and women. METHODS: Charts of 220 patients with
      open globe injuries presenting to the Massachusetts Eye and Ear Infirmary during
      a three-year period were retrospectively reviewed. The data were analyzed with
      respect to gender, type of open globe injury (penetrating, perforating, or
      rupture), and mechanism of globe injury (projectile, non-projectile, assault,
      fall, sports, motor vehicle crash). RESULTS: The majority (78.6%) of patients
      were men. Women with open globe injuries were older (median age 73 years) than
      men (median age 36 years). Men were more likely to suffer from penetrating
      injuries (69.9%) while women were more likely to experience blunt globe rupture
      (68.1%). Projectile objects accounted for the majority of open globe injuries in
      men (54.9%) and were an infrequent cause in women (4.3%). Nearly one-third
      (31.8%) of the projectile injuries in men were work-related, and 19.7% occurred
      during home improvement projects. Compared with men, falls were more frequently
      responsible for globe injuries in women (55.3% versus 8.1%). Injuries limited to
      the cornea were more common in men than women (46.2% versus 23.4%), while more
      posterior globe injuries were more common among women (46.8% versus 28.3% men).
      Women were more likely than men to have poor visual acuity at 3 months after
      injury. CONCLUSIONS: The causes and patterns of open globe injuries differ
      between men and women. In this series, the majority of injuries to men were
      caused by projectile objects related to work or home improvement projects. Open
      globe injuries in women were most often resulted from fall, and were more likely
      to cause rupture posterior to the limbus.

PMID- 16096560
TI  - Cervical spine clearance in blunt trauma: evaluation of a computed tomography
      based protocol.
AB  - BACKGROUND: Prompt identification of cervical spine injuries has been a critical
      issue in trauma management. In 1998, the authors developed a new protocol to
      evaluate cervical spines in blunt trauma. This protocol relies on clinical
      clearance for appropriate patients and helical computed tomography instead of
      plain radiographs for patients who cannot be clinically cleared. The authors then
      prospectively collected data on all cervical spine evaluations to assess the
      sensitivity and specificity of their approach. METHODS: Any patient without
      clinical evidence of neurologic injury, alcohol or drug intoxication, or
      distracting injury underwent cervical spine evaluation by clinical examination.
      Patients who did not meet these criteria underwent helical computed tomographic
      scanning of the entire cervical spine. For patients who had neurologic deficits,
      a magnetic resonance image was obtained. If the patient was not evaluable
      secondary to coma, the computed tomographic scan was without abnormality, and the
      patient was moving all four extremities at arrival in the emergency department,
      the cervical spine was cleared, and spinal precautions were removed. Data were
      collected for all patients admitted to Santa Barbara Cottage Hospital trauma
      service between 1999 and 2002. The authors selected for analysis patients with
      blunt trauma and further identified those with closed head injuries (Glasgow Coma
      Scale score < 15 and loss of consciousness). In addition, all blunt cervical
      spine injuries were reviewed. RESULTS: During the period of study, 2,854 trauma
      patients were admitted, of whom 2,603 (91%) had blunt trauma. Of these, 1,462
      (56%) had closed head injuries. One hundred patients (7% of patients admitted for
      blunt trauma) had cervical spine or spinal cord injuries, of which 99 were
      identified by the authors' protocol. Only one injury was not appreciated in a
      patient with syringomyelia. Fifteen percent of patients with spinal cord injury
      had no radiographic abnormality; all of these patients presented with neurologic
      deficits. The sensitivity for detecting cervical spine injury was thus 99%, and
      the specificity was 100%. The risk of missing a cervical spine injury in these
      blunt trauma patients was 0.04%. The authors missed no spine injuries in patients
      with head injuries. CONCLUSION: The use of the authors' protocol resulted in
      excellent sensitivity and specificity in detecting cervical spine injuries. In
      addition, it allowed early removal of spinal precautions.

PMID- 16096561
TI  - Percutaneous screw fixation for unstable scaphoid fractures.
AB  - BACKGROUND: The technique of percutaneous screw fixation, with increasing
      popularity, has been successfully conducted in non-displaced, stable scaphoid
      fractures resulting in shortened immobilization duration and prompt functional
      retrieval. The purpose of this study was to evaluate the surgical technique and
      to explore the potential benefits of using percutaneous screw fixation in
      unstable scaphoid fractures. METHODS: Eleven of 97 patients with scaphoid
      fractures surgically treated between 1994 and 2002 were enrolled in this study.
      All were acute unstable fractures and underwent closed reduction and percutaneous
      screw fixation. All the records were meticulously reviewed and reported,
      including the complete radiographic examination before and after operation, time
      to fracture union, wrist motion, grip strength, and time of return to work, as
      well as overall patient satisfaction at the time of the most recent follow-up.
      RESULTS: Eleven fractures in an equal number of patients were followed up for a
      mean period of 1.6 years. All fractures acquired radiographic union in an average
      of 10.6 weeks. The modified Mayo Wrist score averaged 88.2. The functional result
      was ranked as excellent in 6 patients, and good in 5 patients. All returned to
      work or the pre-injury level of activity, and were satisfied with the surgical
      outcome. CONCLUSION: The technique of percutaneous screw fixation was
      successfully used to treat 11 unstable scaphoid fractures. The encouraging
      outcome of this treatment option and the prompt functional recovery deserve
      further investigation. Further randomized prospective studies to explore the
      specific indications and ubiquitous benefits of the technique presented herein
      are recommended.

PMID- 16096562
TI  - Trauma patient hospital-associated infections: risks and outcomes.
AB  - BACKGROUND: Trauma patients with surgical procedures, acute lung injury (ALI),
      systemic inflammatory response syndrome (SIRS), and longer exposure to invasive
      devices may be at increased risk for hospital-associated infection (HAI). HAIs
      have been shown to affect outcome measures, but the extent is not well studied.
      METHODS: An infection control team identified HAIs in trauma patients from 1996
      through 2001. The authors evaluated the relation of HAI to surgical procedures,
      ALI, SIRS, and device exposure time by comparing groups with and without HAI
      using Fisher's exact and Mann-Whitney tests. Using multiple linear and logistic
      regressions, the authors evaluated associations of HAI, age, and Injury Severity
      Score (ISS) with length of stay (LOS), cost of care, and mortality. They used Cox
      proportional hazard regression to further explore the relations of HAI, age, and
      ISS to LOS. RESULTS: In 501 of 5,537 trauma patients with HAI (9.1%), the percent
      having surgical procedures, ALI, and SIRS was significantly higher (p < 0.001).
      Exposure to all devices studied was significantly longer (p < 0.001) in HAI
      patients. When the population was controlled for age and ISS, HAI patients had
      longer lengths of stay (LOSs) and higher costs. Age had less effect than ISS on
      LOS, and the effect of increases in age was greater as ISS increased. ISS had a
      greater effect than HAIs on LOS. HAIs increased LOS more in patients less
      severely injured. When comparing patients with and without HAI, no difference in
      mortality rates was detected. CONCLUSION: In this study of trauma patients, ISS
      had the greatest effect on LOS, but increased age and presence of HAI did
      increase LOS and cost of care. HAI increased LOS more in the less severely
      injured patients.

PMID- 16096563
TI  - Impact of the terrorist bombings of the Hong Kong Shanghai Bank Corporation
      headquarters and the British Consulate on two hospitals in Istanbul, Turkey, in
      November 2003.
AB  - BACKGROUND: The authors sought to estimate the impact of the terrorist bombings
      of the Hong Kong Shanghai Banking Corporation headquarters and the British
      consulate in Istanbul, Turkey, on November 20, 2003, on two nearby hospitals, in
      terms of epidemiologic outcomes, resource utilization, and time course of
      emergency needs. METHODS: The authors used data from hospital records of injured
      survivors who used the emergency departments (EDs) at the Taksim Education and
      Research State Hospital (TERSH) and the American Hospital (AH) in Istanbul on
      November 20, 2003, to determine the totals and rates of mortality (early, late,
      and critical), injury, critical injury (Injury Severity Score > 15), ED use,
      hospitalization, operative care, and in-hospital overtriage and the time
      intervals of ED arrival. RESULTS: The TERSH received 184 victims in the first
      hour after the initial blast, of which 88 (48%) were brought by emergency medical
      services, 171 (93%) had lacerations, 7 (4%) had penetrating eye injuries, 28
      (15%) were hospitalized, 18 (10%) received operative care, and 7 (4%) were
      critically injured. Three deaths occurred in critically injured survivors,
      including one early death in the operating room and two late deaths on days 5 and
      6. The AH received 16 victims, of which 14 (88%) had lacerations, 3 (19%) were
      hospitalized, 2 (13%) received operative care, and 1 (6%) was critically injured.
      An additional 4 victims were transferred to the AH from other hospitals, of which
      3 were hospitalized and none were critically injured. No early or late deaths
      occurred. CONCLUSION: Mortality, injury, and hospitalization rates at both
      hospitals were consistent with previous reports of open-air mass-casualty
      terrorist bombings. The TERSH experienced an unprecedented demand for ED surge
      capacity in an open-air bombing.

PMID- 16096564
TI  - Effect of body armor on simulated landmine blasts to cadaveric legs.
AB  - BACKGROUND: Antipersonnel landmine protective footwear relies on blast deflection
      or on exaggerated standoff between the foot and the explosive. Neither design has
      been tested for clinical effectiveness. METHODS: 4 cadaveric lower extremities--3
      fitted with a Koflach boot incorporating TABRE (Technology for Attenuating Blast
      Related Energy) were subjected to controlled blast with charges of up to 100 g
      trinitrotoluene (TNT). The blasts were recorded by a digital recording system.
      All legs were X-rayed and underwent computed tomography scanning before and after
      testing. RESULTS: TABRE-protected limbs directly subjected to the blast
      hyperextended at the knee during firing. Injuries showed a pattern of open tibial
      fractures (Gustilo grade I, II), of multiple calcaneal (Sanders Type III, IV),
      and fibular fractures and of the tibial plateau, but showed no traumatic
      amputation. CONCLUSIONS: Development of protective footwear against landmine
      blast is feasible. From medium mines up to charges of 100 g TNT limb salvage may
      be possible.

PMID- 16096565
TI  - Epimysium and perimysium in suturing in skeletal muscle lacerations.
AB  - BACKGROUND: Direct muscle belly trauma is common. Selecting optimal methods for
      surgical repair of muscle disruption is difficult because reliable methods have
      not been established. Suturing tendon offers strong repairs, but epimysium and
      perimysium, the connective tissues that coalesce to form tendons, offer unknown
      repair strength. The purpose of this study was to compare biomechanical
      properties of repaired muscle in transected muscle bellies with epimysium and
      perimysium. METHODS: The authors surgically repaired with figure-eight stitches
      in both epimysium and perimysium groups. Individual stitches were placed in
      lacerated quadriceps bellies from a euthanized pig and were tensioned on a
      biomechanical machine. Maximum loads and strains were measured, and failure
      mechanisms were recorded. RESULTS: Loads and strains for repairs with epimysium
      were higher than those for repairs with perimysium. Failure mechanisms were
      significantly different between groups. CONCLUSION: These data showed that
      epimysium incorporation into suturing improves capacity to bear forces compared
      with perimysium incorporation.

PMID- 16096566
TI  - Recovery after musculoskeletal trauma in men and women.
AB  - BACKGROUND: Recent work has suggested that women are more at risk of impaired
      outcome after traumatic injuries. This would suggest that resources should be
      targeted at female trauma patients to optimize their outcomes. We wished to
      explore the physical and psychological outcomes of women treated in our trauma
      unit. METHODS: The Grampian Trauma Outcomes Study recruited patients aged 16 to
      70 years with musculoskeletal injuries. Patients with significant head injuries,
      alcohol intoxication, or low-energy osteoporotic fractures were excluded. Of 227
      patients approached, 200 were recruited to the study. Patients were asked to
      complete physical and psychosocial (Short Form-36 and Musculoskeletal Function
      Assessment) and psychological (General Health Questionnaire) outcomes measures at
      initial assessment and at 2- and 6-month follow-up. RESULTS: Of the 200 patients,
      79% completed 2-month follow-up and 75% completed 6-month follow-up. There were
      no significant differences in the outcomes scores between male and female
      patients at either of the follow-up points. CONCLUSION: From our study, women do
      not appear to have impaired recovery after trauma as compared with men. Larger
      scale studies are required to assess the need to target specific resources toward
      the treatment of female trauma victims.

PMID- 16096567
TI  - Mortality from isolated civilian penetrating extremity injury.
AB  - BACKGROUND: Although studies have ascertained that ten percent of soldiers killed
      in battle bleed to death from extremity wounds, little data exists on
      exsanguination and mortality from extremity injuries in civilian trauma. This
      study examined the treatment course and outcomes of civilian patients who appear
      to have exsanguinated from isolated penetrating extremity injuries. METHODS: Five
      and 1/2 years' data (Aug 1994 to Dec 1999) were reviewed from two Level I trauma
      centers that receive 95% of trauma patients in metropolitan Houston, TX. Records
      (hospital trauma registries, emergency medical system (EMS) and medical examiner
      data) were reviewed on all patients with isolated extremity injuries who arrived
      dead at the trauma center or underwent cardiopulmonary resuscitation (CPR) or
      emergency center thoracotomy (ECT). RESULTS: Fourteen patients meeting inclusion
      criteria were identified from over 75,000 trauma emergency center (EC) visits.
      Average age was 31 years and 93% were males. Gunshot wounds accounted for 50% of
      the injuries. The exsanguinating wound was in the lower extremity in 10/14 (71%)
      patients and proximal to the elbow or knee in 12/14 (86%). Ten (71%) had both a
      major artery and vein injured; one had only a venous injury. Prehospital
      hemorrhage control was primarily by gauze dressings. Twelve (86%) had "signs of
      life" in the field, but none had a discernable blood pressure or pulse upon
      arrival at the EC. Prehospital intravenous access was not obtained in 10 patients
      (71%). Nine patients underwent ECT, and nine were initially resuscitated (eight
      with ECT and one with CPR). Those undergoing operative repair received an average
      of 26 +/- 14 units of packed red blood cells. All patients died, 93% succumbing
      within 12 hours. CONCLUSION: Although rare, death from isolated extremity
      injuries does occur in the civilian population. The majority of injuries that
      lead to immediate death are proximal injuries of the lower extremities. The cause
      of death in this series appears to have been exsanguination, although definitive
      etiology cannot be discerned. Intravenous access was not obtainable in the
      majority of patients. Eight patients (57%) had bleeding from a site that
      anatomically might have been amenable to tourniquet control. Patients presenting
      to the EC without any detectable blood pressure and who received either CPR or EC
      thoracotomy all died.

PMID- 16096568
TI  - Outcome and quality of life 5 years after major trauma.
AB  - BACKGROUND: This study aimed to determine quality of life after injury and
      identify factors potentially associated with outcome. METHODS: Five years after
      injury from blunt or penetrating trauma, patients received a questionnaire based
      on the SF-36 Health Survey. RESULTS: Two hundred five patients (83%) replied.
      Most were men, median age 39 years, 93% injured by blunt energy, median Injury
      Severity Score 14 (range 9-57). Mean SF-36 scores were significantly lower than
      in a matched reference group. Poor outcome was associated with: in-hospital days,
      intensive care days, surgical procedures, in-hospital major complications, age,
      recurrent injury, and inadequate information. Subjects reported considerable
      physical (68%) and psychologic (41%) disabilities. Near half reported need of
      improved follow-up care. Injury severity did not predict poor health-related
      quality of life 5 years later. CONCLUSION: Adequate information, sufficient pain
      management and follow-up by trauma specialist teams are needed. Certain factors
      can help identify patients in need of additional help and support.

PMID- 16096569
TI  - Management of esophageal perforation in a sword swallower: a case report and
      review of the literature.

PMID- 16096570
TI  - Extensive in utero traumatic subarachnoid haemorrhage and abruptio placentae.

PMID- 16096571
TI  - Posttraumatic pseudoaneurysm of the hepatic artery: treatment with ultrasound
      guided percutaneous transhepatic thrombin injection.

PMID- 16096572
TI  - Endovascular stent in the acute treatment of blunt renal arterial injury.

PMID- 16096573
TI  - Penetrating trauma to a persistent sciatic artery.

PMID- 16096574
TI  - Compression nailing of ulnar nonunion after Monteggia lesion.

PMID- 16096575
TI  - Mount Fuji sign on CT following trauma.

PMID- 16096577
TI  - Functional neuroimaging endpoints in drug development.

PMID- 16096578
TI  - Voxel-based assessment of spinal tap test-induced regional cerebral blood flow
      changes in normal pressure hydrocephalus.
AB  - OBJECTIVE: Normal pressure hydrocephalus (NPH) is a cause of dementia that may be
      amended by medical intervention. Its diagnosis is therefore of major importance
      and the establishment of response criteria to cerebrospinal fluid (CSF) shunting
      is essential. One of these criteria is the clinical response to spinal tap. The
      accuracy of the spinal tap test could potentially be improved by adding
      neuroimaging of regional cerebral blood flow (rCBF) changes to the response
      criteria. Statistical parametric mapping (SPM) is a voxel-based method of image
      analysis that may be used to statistically assess the significance of rCBF
      changes. The objective of this study was to evaluate, by SPM, spinal tap test
      induced rCBF changes in patients with NPH syndrome. METHODS: Forty patients with
      NPH syndrome underwent hexamethylpropylene amine oxime (HMPAO) brain single
      photon emission computed tomography (SPECT) before and after a spinal tap test (1
      day split-dose protocol). The differences in rCBF between these pairs of scans
      were analysed by SPM in the whole group and between subgroups divided according
      to gait improvement at the spinal tap test. RESULTS: In the whole group of
      patients, there was no statistical difference between pre- and post-spinal tap
      SPECT images. SPM analysis of patients grouped as a function of their clinical
      response to the spinal tap test revealed a significant post-spinal tap rCBF
      increase in the bilateral dorsolateral frontal and left mesiotemporal cortex in
      clinically responding compared with non-responding patients. CONCLUSION:
      According to SPM analysis, gait improvement at the spinal tap test in patients
      with NPH syndrome is associated with an rCBF increase localized in the bilateral
      dorsolateral frontal and left mesiotemporal cortex.

PMID- 16096579
TI  - Detection of hibernate myocardium by 99mTc sestamibi gated SPECT during low-dose
      dobutamine infusion plus nitrate in patients with first acute myocardial
      infarction.
AB  - AIM: To investigate the role of Tc-MIBI gated SPECT imaging following the
      administration of low-dose dobutamine plus nitrate (LDD+nitrate) in the
      assessment of left ventricular function and the perfusion of hibernate myocardial
      tissue. METHODS: The study group comprised 29 patients diagnosed as having acute
      myocardial infarction. In the first month post-infarction, Tc-MIBI gated SPECT
      imaging was performed in all patients at rest-dobutamine stress and LDD+nitrate.
      Ejection fraction, end diastolic volume (EDV), end systolic volume (ESV), stroke
      volume, volume, extent score, and reversibility score values were calculated.
      RESULTS: The findings of Tc-MIBI gated SPECT imaging following the administration
      of LDD+nitrate and the rest Tc-MIBI gated SPECT findings revealed that while the
      levels of ejection fraction (P=0.004) and reversibility score (P=0.000) increased
      significantly, there was a significant decrease in EDV (P=0.001), ESV (P=0.001),
      volume (P=0.017), stroke volume (P=0.257) and extent score (P=0.039) values.
      CONCLUSION: The use of Tc-MIBI gated SPECT concomitantly with the administration
      of LDD+nitrate is useful in the determination of myocardial hibernation in
      patients with left ventricular failure following acute myocardial infarction.

PMID- 16096580
TI  - Long-term effects of antilipidaemic therapy on left ventricular function in
      patients with dyslipidaemia: multigated radionuclide ventriculography study.
AB  - AIM: It has been reported that dyslipidaemia impairs left ventricular systolic
      (LVs) and diastolic (LVd) functions, irrespective of atherogenic effects, in the
      setting of coronary artery disease. The aim of the present study was to evaluate
      the effects of anti-lipidaemic therapy on LVs and LVd functions by means of
      multigated radionuclide ventriculography (RNV) in subjects with signs of
      dyslipidaemia and with preserved left ventricular function. METHODS: Eighteen
      patients with dyslipidaemia (eight men, 10 women, mean age 50+/-10 years) were
      included in the study. While the clinical examination and treadmill exercise test
      results were normal in all patients, low-density lipoprotein levels exceeded 160
      mg . dl. Patients with medical conditions including coronary artery disease,
      hypertension, diabetes, cardiomyopathy and valvular heart disease which would
      influence left ventricular function were excluded from the study. RNV was
      performed in all subjects, taking into account the best septal position to
      differentiate the left ventricle from the right ventricle. The following
      parameters were calculated: ejection fraction, peak ejection rate (PER), time to
      peak ejection (TPER), a ejection rate (aER), a ejection fraction (aEF), Peak
      filling rate (PFR), time to peak filling rate (TPFR), a filling rate (aFR), a
      filling fraction (aFF). RESULTS: The low-density lipoprotein value decreased and
      the high-density lipoprotein value increased after statin therapy (P<0.001 and
      P<0.003, respectively). PER, aER and aFF significantly increased and TPER
      decreased as a consequence of statin therapy (respectively, P<0.05, P<0.05,
      P<0.05 P<0.05). CONCLUSION: Anti-lipidaemic therapy is effective in dyslipidaemic
      patients. RNV is a useful and non-invasive method for monitoring changes in
      ventricular function following anti-lipidaemic treatment strategies.

PMID- 16096581
TI  - The efficacy of 99mTc-HIG for sentinel lymph node mapping in breast cancer
      patients.
AB  - OBJECTIVE: To evaluate the efficacy of Tc-HIG on SLN identification in patients
      with early-stage breast cancer. MATERIALS AND METHODS: Seventeen women (18
      tumours) with early-stage breast cancer were included. On the day of the
      operation, 111 MBq Tc-HIG was injected around the tumour or biopsy scar in all
      patients. Subsequently, dynamic lymphoscintigraphic images were taken for 30 min.
      After this, static images were recorded at 15-20 min intervals until the SLN was
      visualized. Patients were taken to the operating room 2-4 h after
      radiopharmaceutical injection. Before the incision, 5 ml of isosulfan blue dye
      solution was injected peritumourally in all subjects. Aided by blue dye and gamma
      probe SLN detection was done during the operation. RESULTS: In 17/18 tumours, SLN
      was detected with Tc-HIG lymphoscintigraphy. The mean visualization time for
      axillary SLNs was 49.94+/-11.25 min and for internal mammary SLNs was 52.50+/
      10.60 min. In 15 of the tumours, only one SLN was detected in the axillary
      region. However, in two tumours, SLNs were found in both axillary and internal
      mammary regions. With blue dye mapping, axillary SLNs were found in 17/18
      tumours. With the application of intraoperative gamma probe, all axillary and
      internal mammary SLNs were detected in 18 tumours. CONCLUSION: We conclude that
      Tc-HIG may be a suitable agent for SLN detection by lymphoscintigraphy and
      intraoperative gamma probe application in early-stage breast cancer patients.

PMID- 16096582
TI  - Intra-individual variability of cardiac uptake on serial whole-body 18F-FDG PET.
AB  - OBJECTIVE: To measure the variability of cardiac uptake on serial whole-body F
      FDG PET scans. METHODS: Two hundred and eighteen whole-body PET scans were
      performed in 47 patients with different primary malignancies between October 1996
      and April 2003 on a dedicated PET system. The number of scans per patient ranged
      between four and nine. Two experienced nuclear medicine physicians reviewed the
      scans retrospectively using the non-attenuation corrected images to assess the
      cardiac FDG uptake. Patients with cardiac uptake less or equal to lung uptake
      were assigned in the "low" uptake group, and those with cardiac uptake more than
      the lung uptake were assigned to the "high" uptake group. The reproducibility of
      cardiac uptake on serial whole-body PET scans and the effect of age, sex, weight,
      diabetes and primary diagnosis on cardiac uptake was evaluated. RESULTS: There
      was very good reproducibility (intra-class correlation coefficient=0.77) of
      individual cardiac FDG uptake on serial whole-body PET scans. Diabetics (n=6) in
      comparison to non-diabetics were less likely to have high cardiac uptake (odds
      ratio (OR)=0.24, P<0.05). Patients with lymphoma (n=12) in comparison to patients
      with other primary diagnoses were more likely to have high cardiac uptake
      (OR=8.6, P<0.05). There was no association between cardiac uptake and age, sex or
      weight. CONCLUSION: Cardiac FDG uptake on whole-body PET does not appear to
      change significantly over time. It is likely that uptake is determined by
      individual characteristics; these likely include diabetes and primary diagnosis
      of lymphoma.

PMID- 16096583
TI  - An efficient, reproducible and fast preparation of 188Re-anti-CD20 for the
      treatment of non-Hodgkin's lymphoma.
AB  - BACKGROUND: Therapies using Y-anti-CD20 or I-anti-CD20 have demonstrated their
      efficacy in patients with B-cell non-Hodgkin's lymphoma. Re is a radionuclide
      useful for radioimmunotherapy. AIM: To develop a procedure for efficient
      labelling of anti-CD20 with Re from lyophilized formulations to achieve high
      radiochemical yield, high specific activity and preservation of the molecular
      recognition after a simple kit reconstitution without further purification.
      METHODS: Re-anti-CD20 was prepared by a direct labelling method using sodium
      tartrate as a weak competing ligand. Different lyophilized formulations were
      prepared to optimize tartrate and stannous chloride concentration, pH and
      reaction time. To evaluate the biological recognition a comparative study of the
      in-vitro binding of Re-anti-CD20, I-anti-CD20 (positive control) and Re-anti-CEA
      (negative control) to normal B lymphocytes was performed. Biodistribution studies
      in normal mice were accomplished to assess the in-vivo Re-anti-CD20 complex
      stability. RESULTS: Re labelled anti-CD20 was obtained with high radiochemical
      purities (>97%) and high specific activity (0.5-0.7 GBq . mg) 1-1.5 h after
      addition of sodium perrhenate solution to a kit containing 4.4 muM anti-CD20, 4
      mM anhydrous stannous chloride, and 140 mM dihydrate sodium tartrate at pH 4. The
      binding of Re-anti-CD20 to cells was in the same range as I-anti-CD20 (>80%) and
      was significantly different to cell binding of Re-anti-CEA (<10%). No evidence of
      free Re release was found at 2, 4 and 24 h after Re-anti-CD20 administration in
      mice. Lyophilized kits showed high stability during the storage at 4 degrees C
      for 6 months. CONCLUSIONS: Optimal reaction conditions were defined enabling high
      radiochemical purities of Re-anti-CD20 to be obtained routinely and therefore
      potentially useful in the treatment of non-Hodgkin's lymphoma.

PMID- 16096584
TI  - Enhanced perfusion defect clarity and inhomogeneity in smokers' lungs with deep
      inspiratory breath-hold perfusion SPECT images.
AB  - PURPOSE: Deep-inspiratory breath-hold (DIBrH) Tc-99m-macroaggregated albumin
      (MAA) SPECT images were developed to accurately evaluate perfusion impairment in
      smokers' lungs. METHODS: DIBrH SPECT was performed in 28 smokers with or without
      low attenuation areas (LAA) on CT images, using a triple-headed SPECT system and
      a laser light respiratory tracking device. DIBrH SPECT images were reconstructed
      from every 4 degrees projection of five adequate 360 degrees projection data sets
      with almost the same respiratory dimension at 20 sec DIBrH. Perfusion defect
      clarity was assessed by the lesion (defect)-to-contralateral normal lung count
      ratios (L/N ratios). Perfusion inhomogeneity was assessed by the coefficient of
      variation (CV) values of pixel counts and correlated with the diffusing capacity
      of the lungs for carbon monoxide/alveolar volume (DLCO/VA) ratios. The results
      were compared with those on conventional images. RESULTS: Five DIBrH projection
      data sets with minimal dimension differences of 2.9+/-0.6 mm were obtained in all
      subjects. DIBrH images enhanced perfusion defects compared with conventional
      images, with significantly higher L/N ratios (P<0.0001), and detected a total of
      109 (26.9%) additional detects (513 vs. 404), with excellent inter-observer
      agreement (kappa value of 0.816). CV values in the smokers' lungs on DIBrH images
      were also significantly higher compared with those on conventional images (0.31+/
      0.10 vs. 0.19+/-0.06, P<0.0001). CV values in smokers on DIBrH images showed a
      significantly closer correlation with DLCO/VA ratios compared with conventional
      images (R = 0.872, P<0.0001 vs. R=0.499, P<0.01). CONCLUSION: By reducing adverse
      effect of respiratory motion, DIBrH SPECT images enhance perfusion defect clarity
      and inhomogeneity, and provide more accurate assessment of impaired perfusion in
      smokers' lungs compared with conventional images.

PMID- 16096585
TI  - A Monte Carlo analysis technique applied to cerebral perfusion SPECT scans.
AB  - OBJECTIVE: Voxel-based techniques are used to provide objective analyses of SPECT
      scans. The aim of this study was to develop a voxel-based analysis technique that
      uses a Monte Carlo method of statistical inference and assess this analysis
      technique for application to cerebral perfusion SPECT scans. METHODS: Assessment
      of the validity of this non-parametric, Monte Carlo method of statistical
      inference has been performed for a range of study designs, image characteristics
      and analysis parameters using phantom SPECT and Gaussian images. The Monte Carlo
      method of statistical inference and the voxel-based analysis technique were
      clinically evaluated for the analysis of individual cerebral perfusion SPECT
      scans using control subject data. In addition, a comparison has been performed
      with an existing analysis package that uses a theoretical parametric method of
      statistical inference (statistical parametric mapping). RESULTS: The Monte Carlo
      method was found to provide accurate statistical inference for phantom SPECT and
      Gaussian images independent of degrees of freedom, acquired counts, image
      smoothness and voxel significance level threshold. The clinical evaluation of the
      analysis of individual cerebral perfusion SPECT scans demonstrated satisfactory
      statistical inference and characterization of perfusion deficits. CONCLUSION: An
      analysis method incorporating a Monte Carlo method of statistical inference has
      been successfully applied for the analysis of cerebral perfusion SPECT scans.

PMID- 16096586
TI  - Compression and reconstruction of sorted PET listmode data.
AB  - BACKGROUND: In nuclear medicine data can be stored in histogram or listmode
      format. The most popular histogram format is the planar projection format. Due to
      the increase in detector blocks, the improved energy resolution and the trends
      towards time of flight, dynamic and gated imaging, it can be more appropriate to
      store the data in listmode format. The size of the storage in this format
      increases linearly with the number of properties (positions, energy, time info)
      while the histogram format increases exponentially. However, the datasize of
      listmode data also increases linearly with the number of coincidences. Due to the
      high number of counts in 3D PET this will lead to very large datasets. Therefore
      a good compression algorithm for listmode data is very important. METHODS: A
      sorting and compression method is proposed to reduce the amount of space needed
      to store the listmode dataset. One event is represented by one number without any
      information loss compared to the original listmode file. The next step is to sort
      all events into an array of increasing numbers. These data are compressed by the
      gzip routine. One of the advantages of 3D PET listmode reconstructions is that
      they result in a more uniform resolution across the field of view (FOV), which is
      not always true for other reconstruction algorithms. This improved resolution is
      shown for the listmode data of a gamma camera operating in PET mode. RESULTS:
      First the effect of positional accuracy in the listmode dataset is evaluated by
      comparing resolution in the reconstructions. It is shown that the highest
      accuracy is not necessary and a significant reduction in the size of the dataset
      can be obtained prior to lossless compression. A further reduction can be
      obtained by using the proposed sorting and compression techniques. It is shown
      that the storage space decreases linearly with the logarithm of the number of
      coincidences. The compression obtained by different acquisition matrices was
      compared. Finally it is shown that the 3D listmode reconstruction of sorted
      listmode data is faster because of improved cache behaviour. The method can be
      applied to any kind of listmode data. The compression factors will improve when
      the ratio of measured events to possible events increases.

PMID- 16096587
TI  - Focal lung uptake of 18F-fluorodeoxyglucose (18F-FDG) without computed tomography
      findings.
AB  - BACKGROUND: Integrated positron emission tomography/computed tomography (PET/CT)
      systems represent a major development allowing functional and anatomical
      information to be acquired in a single examination session and therefore
      providing a more accurate definition of suspected lesion characteristics.
      Together with the increasing number of clinical settings in which PET/CT scans
      have been advocated, however, pitfalls in image interpretation have been
      reported. METHODS: Four female subjects presenting a focal area of increased F
      fluorodeoxyglucose (F-FDG) uptake with no evidence of a corresponding CT
      abnormality were included in the study. PET/CT scans were performed in all cases
      after the administration of 5.3 MBq . kg of F-FDG through a venous cannula.
      RESULTS: Focal high uptake of F-FDG was observed in lung lesions without
      anatomical counterparts on CT in four female cases. The only common feature to
      all was the paravenous injection of the radiotracer. CONCLUSION: The lesions
      detected by PET may be related to distal lung microembolism originating from the
      site of paravenous injection.

PMID- 16096588
TI  - Patients with known or suspected lung cancer: evaluation of clinical management
      changes due to 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET)
      study.
AB  - AIM: To determine prospectively from the referring physician's point of view the
      impact of F-fluorodeoxyglucose positron emission tomography (F-FDG PET) results
      on the management decisions in patients with known or suspected lung cancer.
      METHODS: Seventy-five consecutive patients (58 men, 17 women; age range, 33-82
      years; mean age, 64 years) with a diagnosis of a pulmonary lesion, obtained by
      means of morphological imaging studies and/or cytological sampling, were included
      in the study. The patient population consisted of three groups: (A) patients
      (n=18) with a solitary lung nodule; (B) patients (n=37) with untreated lung
      cancer; and (C) patients (n=20) with treated lung cancer. All were referred for
      whole-body F-FDG PET within 15 days (mean, 11 days) of lung lesion detection. To
      determine whether and how PET findings could modify the treatment strategy, a
      questionnaire was sent to the referring physician before and after the PET
      results. With regard to the treatment strategy, four major options were
      recognized: (1) further diagnostic investigations; (2) medical therapy; (3)
      surgical treatment; (4) wait-and-see. For data analysis, intermodality changes,
      defined as changes between treatment strategies related to PET findings, were
      considered. RESULTS: Before the PET study, the planned management for the overall
      patient population was as follows: further diagnostic investigations in 44 cases
      (58%), medical therapy in 17 (23%), surgical treatment in nine (12%) and wait-and
      see in five (7%). After the PET study, further diagnostic tools were indicated in
      27 cases (36%), medical therapy in 17 (23%), surgical treatment in 28 (37%) and
      wait-and-see in three (4%). Relative to the initially planned strategy, changes
      in patient management after PET imaging occurred in 34 (45%) cases. Overall, the
      most relevant variation after PET concerned the surgical treatment strategy. The
      highest percentage (67%) of changes in management after PET was found in patients
      with a solitary pulmonary nodule; the percentages of changes of the three patient
      groups were significantly different (chi-squared test; P=0.021). CONCLUSIONS: In
      patients with known or suspected lung cancer, F-FDG PET results determined
      significant variations in major clinical management decisions.

PMID- 16096589
TI  - Estimated radiation dose to breast feeding infant following maternal
      administration of 57Co labelled to vitamin B12.
AB  - Administration of a radiopharmaceutical may result in a radiation dose to an
      infant due to ingestion of the radiopharmaceutical secreted in the breast milk.
      Following a maternal administration of Co labelled to vitamin B12
      (cyanocobalamin) as part of a Schilling test an estimate of the absorbed dose to
      a breast feeding infant was calculated. Milk samples were collected from every
      feed in the first 24 h, and at approximately 48 and 72 h post-administration. The
      absorbed dose to the infant's liver (the organ receiving the highest dose) was
      calculated to be 0.23 mGy. The effective dose to the infant was calculated to be
      0.025 mSv, which is considerably lower than the current regulatory limit of 1
      mSv. The Administration of Radioactive Substances Advisory Committee advise that
      the first feed, at approximately 4 h after administration, be discarded. The data
      show that this was unwarranted, and that the peak concentration of Co in the
      breast milk occurred at around 24 h.

PMID- 16096591
TI  - The utility of bedside ultrasound and patient perception in detecting soft tissue
      foreign bodies in children.
AB  - OBJECTIVE: The purpose of the study was to determine if bedside ultrasound (US)
      and perception of wound foreign bodies (FBs) are useful screening tools for
      detecting wound FBs in children. METHODS: Prospective consecutive sample of
      children aged 18 years or younger presenting to a pediatric emergency department
      with wounds considered by the pediatric emergency department attending physician
      to be at risk for FBs was enrolled. Patients were asked if they had FB sensation
      in their wound(s). A bedside US of each wound was performed by the pediatric
      emergency department attending physician. A radiograph of each wound was obtained
      and interpreted by a radiologist blinded to US results and patient perception.
      Wound FBs were defined by the removal of a FB. The utilities of US and US with FB
      perception were compared with radiography for screening for wound FBs.
      Differences in performance characteristics among the 3 modalities were assessed
      using Fisher exact test. RESULTS: One hundred thirty-one wounds were studied in
      105 patients. FBs were identified in 12 wounds (9.2%). A subanalysis was
      performed on patients able to answer questions regarding their perception of
      wound FBs. There were no significant differences in the test performance
      characteristics of bedside US alone compared with radiography for detecting wound
      FBs. Except for specificity, there were no significant differences in the test
      performance characteristics of bedside US combined with perception compared with
      radiography for detecting wound FBs. CONCLUSIONS: Bedside US is comparable to the
      performance of radiography interpreted by an attending pediatric radiologist.
      Bedside US alone or combined with patient perception may be an adequate initial
      screening tool for detecting wound FBs.

PMID- 16096592
TI  - Capnography as a rapid assessment and triage tool for chemical terrorism.
AB  - The assessment and triage of victims of chemical terrorism in the emergency
      department and the prehospital setting has become an important priority. This
      article proposes the use of capnography as a prehospital assessment and triage
      tool for monitoring victims of chemical terrorism and for critically ill
      patients. Capnography provides the ABCs in less than 15 seconds and identifies
      the common complications of chemical terrorism. Further, the reliability of
      capnography is not affected by motion artifact or low perfusion and it is
      accurate and reliable in actively seizing patients. Emergency departments and
      emergency medical services systems should consider adding capnography to their
      chemical terrorism education and training.

PMID- 16096593
TI  - Ankle sprain discharge instructions from the emergency department.
AB  - OBJECTIVES: (1) To describe the incidence of inclusion of early mobilization
      components in emergency department (ED) discharge instructions; (2) to describe
      the prescribed follow-up appointments; and (3) to analyze the differences between
      the treatment of pediatric and adult patients. METHODS: A 1-year retrospective
      chart review of ED records of a large urban hospital was performed. Medical
      records of 374 (95%) of the 397 adult and pediatric patients with ICD-9 code for
      ankle sprains were reviewed (213 males and 171 females, mean age 28.4 +/- 14.5;
      291 adults, 93 pediatric). RESULTS: Sixteen percent of records contained
      discharge instructions that included rest, ice, compression, elevation, and
      medications (RICEM). Twenty percent included RICE. Pediatricians (33.7%) were
      more likely than adult physicians (10.3%) to have given RICEM (P < 0.0001) and
      RICE (P = 0.05, pedi = 45.8%, adult = 13.1%). Follow-up referrals were
      recommended as needed 50% of the time. Follow-up referrals were made to community
      clinics (59%), orthopedic clinic (23%), the ED (14%), and others (4%).
      Pediatricians were more likely to recommend routine scheduled follow up (pedi =
      62%, adult = 47%, P = 0.018), suggest follow-up in a community clinic or doctors
      office (pedi = 68.6%, adult = 51.2%, P < 0.0001), and to recommend earlier follow
      up (pedi = 1.6 weeks +/- 1.1, adult = 2.0 weeks +/- 1.1, P = 0.002) than adult
      physicians. CONCLUSIONS: Programs that train physicians who work in the ED need
      to include education on the proper treatment, rehabilitation, and follow up of
      patients with acute ankle sprains. Providing easy-to-complete discharge
      instruction templates can help providers give patients discharge instructions
      that may help patients minimize the risk of long-term sequelae.

PMID- 16096594
TI  - Human immunodeficiency virus postexposure prophylaxis in child and adolescent
      victims of sexual assault.
AB  - OBJECTIVES: This study was performed at an urban children's hospital to identify
      the characteristics of patients given human immunodeficiency virus (HIV)
      postexposure prophylaxis and describe the adherence and associated side effects
      of HIV prophylaxis in child and adolescent victims of sexual abuse. METHODS: A
      retrospective review of all children presenting for evaluation of suspected
      sexual abuse who were provided HIV prophylaxis between February 1999 and March
      2001 was performed. Measured variables included risk factors for transmission of
      HIV, antiretrovirals prescribed and their side effects, initial and follow-up
      laboratory results, and compliance. RESULTS: The medical records of 34 patients
      were examined. Assault by a stranger was the most common risk factor prompting
      prophylaxis. Zidovudine and lamivudine were prescribed for 32 patients (94%).
      Only 17 patients (50%) kept at least 1 follow-up appointment; 8 patients (24%)
      finished the entire course of prophylaxis. Side effects were reported in 11 (65%)
      of 17 patients, but only 1 patient was known to have stopped prophylaxis because
      of subjective side effects, and 1 patient was removed from prophylaxis due to
      laboratory abnormality. CONCLUSIONS: Adherence to medication regimen and follow
      up appointments in victims of suspected sexual abuse who are provided HIV
      prophylaxis is poor. The medications are associated with several side effects,
      but rarely do the side effects prohibit their use. Given difficulties with
      compliance, potential adverse effects of medications, and the high cost of
      treatment, care should be taken in offering prophylaxis to only those at
      increased risk for transmission of disease.

PMID- 16096595
TI  - Differences in herbal and dietary supplement use in the Hispanic and non-Hispanic
      pediatric populations.
AB  - BACKGROUND: Complementary and alternative medical therapies are becoming
      increasingly popular in the general population. OBJECTIVE: To describe the
      cultural differences in the use of herbal and dietary supplements in the Hispanic
      and non-Hispanic-Caucasian outpatient pediatric populations. METHODS:
      Questionnaires were administered over a 2-month period to a convenience sample of
      adolescents and parents of patients younger than 12 years, presenting to an
      emergency department, an urban private pediatric practice, and a community-based
      clinic. RESULTS: There were 643 surveys completed. Ethnic distribution was 65%
      Caucasian, 27% Hispanic, 2% Pacific Islander, and 1% each Asian, African American
      and Native American. Mean respondent age was 30.8 years. Mean child age was 4.6
      years; 51% were male. Use of nonprescribed dietary supplements was significantly
      greater in Hispanic (33%) versus Caucasian children (9%) (P < 0.01); most
      commonly used supplements were herbal teas (56%) and echinacea (14%). More
      Hispanic respondents reported receiving information on herbal preparations from a
      family member compared with non-Hispanic patients (56.0% vs. 18.7%).
      Complementary and alternative medicine use had not been discussed with a health
      care provider by 38% of the total users and 47% of those thought it not important
      to do so. CONCLUSIONS: There is significant use of complementary and alternative
      medicine in the pediatric population, and herbal and dietary supplement use
      varies between Hispanic and Caucasian children. In addition, this dietary
      supplement use is often not discussed with health care providers. These factors
      should be taken into consideration by all health care providers.

PMID- 16096596
TI  - "Doctor" or "doctora": do patients care?
AB  - BACKGROUND: The topic of gender and medical care is receiving increased attention
      but has not been studied in children. We noticed that several children undergoing
      laceration repair in emergency department requested to be sutured by a female
      physician. This study attempted to find gender preferences of children and
      parents for the physician in the emergency department. OBJECTIVE: We undertook
      this study to determine whether pediatric patients or their parents have a
      preference for physicians of a particular gender. We also tried to determine
      whether they would be willing to wait longer to be seen to accommodate their
      choice. METHODS: A total of 200 children aged between 8 and 13 years presenting
      to our pediatric emergency department for laceration repair were enrolled. With
      the knowledge and consent of their parents, the enrolled children were given a
      short questionnaire. They were asked, if they had a choice, would they prefer to
      have a male or a female doctor or would they prefer the doctor with the most
      experience. Their parents were also then given the questionnaire. They were also
      asked if they would be willing to wait longer to be seen by the doctor of their
      choice. RESULTS: The study sample comprised 200 children, 139 boys and 61 girls.
      Among boys, 78% (n = 109) said they would prefer a female physician. Only 21% (n
      = 30) preferred a male physician. Among girls, 80% (n = 49) reported they would
      prefer a female physician, 20% (n = 12) preferred a male physician. None of the
      children surveyed wanted the "best" physician. When the parents were surveyed,
      60% (n = 120) preferred a male physician as compared with 19% (n = 38) who
      expressed a preference for female physician. Only 21% (n = 42) of parents desired
      the most experienced physician of either sex to repair the laceration. All the
      parents who expressed a preference for the "most experienced" physician said they
      were willing to wait (42/42) until that physician was available as compared with
      less than a third of parents who were willing to wait for the physician of a
      specific gender (44/158). CONCLUSIONS: Most children (79%) preferred a female
      physician for their sutures, whereas parents overall (60%) appeared to prefer a
      male physician. The children did not appear to care if the physician was the
      "best." Surprisingly, many parents also chose physician gender rather than
      physician experience. One hundred percent of the parents who chose the most
      experienced physician were willing to wait longer to be seen as compared with 29%
      who preferred a physician of a particular gender.

PMID- 16096597
TI  - The use of evidence-based medicine in the management of acutely ill children.
AB  - OBJECTIVES: To determine the extent to which emergency medicine physicians are
      exposed to and implement evidence-based medicine (EBM). METHODS: A 2-part, self
      administered questionnaire was sent to 375 randomly selected emergency physicians
      (125 PEM Fellows, 125 AAP Section of Emergency Medicine, 125 American College of
      Emergency Physicians). The first part focused on the physician's experience with
      EBM and the second part included 2 clinical scenarios to determine their decision
      making process. Respondents were considered either junior physicians (practicing
      <5 years since residency training) or senior physicians (practicing for > or =5
      years). RESULTS: Of the 375 questionnaires sent, 22 were not eligible for
      analysis. Two-hundred ten of the remaining 353 (59%) questionnaires were
      returned.Ninety-five percent of all respondents have been exposed to EBM. There
      was no significant difference between junior and senior physicians in their
      familiarity and application of secondary EBM summaries. Although more junior
      physicians believe that greater than half of their clinical practice is evidenced
      based compared with senior physicians [49% (95% CI 41-58%) vs. 27% (95% CI 19
      38%)], in responding to the clinical scenarios, there was no difference in the
      use of an EBM resource between junior and senior physicians in the use of
      intravenous magnesium sulfate for status asthmaticus [50% (95% CI 41-59%) vs. 48%
      (95% CI 37-59%)] or in the workup of fever in a 10-month-old [62% (95% CI 53-70%)
      vs. 54% (95% CI 44-64%)]. Ninety-three percent of respondents felt "time
      constraints in a busy ED" was the most prominent obstacle to the use of EBM.
      CONCLUSIONS: Although a majority of emergency medicine physicians report having
      been exposed to EBM, respondents tended not to use EBM in the management of
      acutely ill children, regardless of years of experience.

PMID- 16096598
TI  - Artificial nail aspiration masquerading as refractory croup.
AB  - Infants with an aspirated foreign body who present with acute onset of obstructed
      airflow should be readily diagnosed. When aspirated foreign body is overlooked,
      patients may present with recurrent inspiratory, biphasic, or expiratory stridor.
      We report an infant who repeatedly presented with varying degrees of inspiratory
      stridor. The diagnosis of aspirated foreign body was hampered by the presence of
      respiratory syncytial virus infection with the initial episode.

PMID- 16096599
TI  - Ataxia and shaking in a 2-year-old girl: acute marijuana intoxication presenting
      as seizure.

PMID- 16096600
TI  - Omeprazole-induced hepatitis.
AB  - Omeprazole; the first proton pump inhibitor (PPI) showing an effective acid
      inhibitory ability, provides the satisfactory therapy either in gastro-esophageal
      reflux symptom relief or in healing of erosive esophagitis. It's also effective
      in peptic ulcer disease. Up to date, omeprazole efficacy and safety are well
      established in many trials. Omeprazole-related hepatotoxicity is not very well
      recognized especially in pediatric population. We report a child who developed
      hepatitis following omeprazole intake. We believe that this is the first case
      report of omeprazole-induced hepatitis in pediatric population.

PMID- 16096601
TI  - Acute glaucoma masquerading as migraine in a child.

PMID- 16096602
TI  - Severe methemoglobinemia due to food intoxication in infants.
AB  - The purpose of this case report is to illustrate food intoxication in infants as
      a consequence of fennel ingestion. Four cases of methemoglobinemia (MetHb) are
      presented here. Each patient ate homemade fennel puree a few hours prior to
      arriving to the emergency department with cyanosis unresponsive to oxygen, in the
      absence of suspected cyanotic heart disease. All 4 patients received treatment
      with methylene blue and fully recovered. Our cases emphasize that improper
      handling and storing of vegetables can lead to life-threatening MetHb.

PMID- 16096603
TI  - "Don't jump on the bed".
AB  - Jumping on the bed is a common childhood behavior. However, little is known about
      the potential for traumatic injury sustainable as a consequence of this behavior
      save for an understanding of the risk of injury related to falling from a bed,
      and a growing body of literature related to trampoline injuries. We report a case
      of a "grid" wire puncture injury that required a minor incision to affect
      removal. Parents should know about the possibility of this injury secondary to
      jumping on the bed, and pediatricians should know that the grid wires have hooked
      ends that may require incision to facilitate their removal.

PMID- 16096604
TI  - Acute abdomen: previous urinary tract infection.

PMID- 16096605
TI  - ECGs in the ED.

PMID- 16096606
TI  - Myasthenia gravis: myasthenia vs. cholinergic crisis.
AB  - A serious complication of myasthenia gravis is respiratory failure. This may be
      secondary to an exacerbation of myasthenia (myasthenia crisis) or to treatment
      with excess doses of a cholinesterase inhibitor (cholinergic crisis). Managing
      respiratory failure and differentiating a myasthenia from a cholinergic crisis is
      reviewed. Due to the unpredictable development of respiratory failure,
      hospitalization is recommended for most patients with exacerbations or
      complications of myasthenia gravis.

PMID- 16096607
TI  - Abstracts from the American Academy of Pediatrics Section on Emergency Medicine
      National Conference and Exhibition. October 8-9, 2005.

PMID- 16096608
TI  - Preventing medical errors in pediatric emergency medicine.

PMID- 16096611
TI  - Sonography of thyroid nodules: a "classic pattern" diagnostic approach.
AB  - This article describes an approach to some of the commonly encountered, "classic
      pattern," appearances of both benign and malignant thyroid nodules that are seen
      in day-to-day practice. These appearances include specific nodules that commonly
      need fine needle aspiration (FNA)/biopsy, and other nodules that do not usually
      need FNA/biopsy.

PMID- 16096612
TI  - The sonographic diagnosis of adenomyosis.
AB  - Adenomyosis is a common but under-diagnosed gynecologic condition due to
      hypertrophied myometrial smooth muscle containing ectopic endometrial glands that
      is associated with pelvic pain, menorrhagia, and an enlarged uterus. This is an
      overview of the sonographic and magnetic resonance imaging features that have
      been developed in the diagnosis of adenomyosis emphasizing sonography as the
      initial study performed in the symptomatic patient. These features include
      myometrial heterogeneity, asymmetric thickening of myometrium, cysts, linear
      striations, and an ill-defined endometrium. Both magnetic resonance imaging and
      sonography can now diagnose adenomyosis with a high degree of accuracy so that
      treatment may be instituted specific to the disease process.

PMID- 16096613
TI  - What Is YOUR Diagnosis? Testicular epidermoid cyst.

PMID- 16096614
TI  - Transrectal and transvaginal sonographic intervention of infected pelvic fluid
      collections: a complete approach.
AB  - Infected pelvic fluid collections are relatively common particularly after
      abdominal or pelvic surgery or in patients suffering from benign intestinal
      disease such as diverticulitis, appendicitis, or Crohn's disease. Historically
      the treatment of pelvic abscess has been either laparotomy with lavage or blind
      surgical incision and drainage through the rectal or vaginal wall. More recently,
      computed tomography and ultrasound-guided percutaneous drainage has become the
      procedure of choice, when feasible, for the treatment of pelvic abscess. However,
      many deep pelvic collections are not amenable to percutaneous technique.
      Transrectal or transvaginal ultrasound-guided abscess drainage is a safe and
      effective method used in the treatment of deep pelvic abscesses. The purpose of
      this article is to review the techniques, patient selection, pre- and post
      procedural care, and monitoring aspects of transrectal or transvaginal ultrasound
      guided drainage.

PMID- 16096615
TI  - A practical approach to analyzing focal lesions in the liver.
AB  - Ultrasound evaluation of patients with hepatic masses should extend beyond basic
      lesion detection to characterization and clinical management. A systematic
      approach for hepatic lesion evaluation using ultrasound makes it possible to
      triage patients and, in many cases, leads to definitive diagnosis that may
      eliminate the need for additional imaging.

PMID- 16096637
TI  - Fission yeast MO25 protein is localized at SPB and septum and is essential for
      cell morphogenesis.
AB  - Cell morphogenesis is of fundamental significance in all eukaryotes for
      development, differentiation, and cell proliferation. In fission yeast,
      Drosophila Furry-like Mor2 plays an essential role in cell morphogenesis in
      concert with the NDR/Tricornered kinase Orb6. Mutations of these genes result in
      the loss of cell polarity. Here we show that the conserved proteins, MO25-like
      Pmo25, GC kinase Nak1, Mor2, and Orb6, constitute a morphogenesis network that is
      important for polarity control and cell separation. Intriguingly, Pmo25 was
      localized at the mitotic spindle pole bodies (SPBs) and then underwent
      translocation to the dividing medial region upon cytokinesis. Pmo25 formed a
      complex with Nak1 and was required for both the localization and kinase activity
      of Nak1. Pmo25 and Nak1 in turn were essential for Orb6 kinase activity. Further,
      the Pmo25 localization at the SPBs and the Nak1-Orb6 kinase activities during
      interphase were under the control of the Cdc7 and Sid1 kinases in the septation
      initiation network (SIN), suggesting a functional linkage between SIN and the
      network for cell morphogenesis/separation following cytokinesis.

PMID- 16096638
TI  - A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor
      progression.
AB  - The transcription factor Snail controls epithelial-mesenchymal transitions (EMT)
      by repressing E-cadherin expression and other epithelial genes. However, the
      mechanisms involved in the regulation of Snail function are not fully understood.
      Here we show that lysyl-oxidase-like 2 and 3 (LOXL2 and LOXL3), two members of
      the lysyl-oxidase gene family, interact and cooperate with Snail to downregulate
      E-cadherin expression. Snail's lysine residues 98 and 137 are essential for Snail
      stability, functional cooperation with LOXL2/3 and induction of EMT.
      Overexpression of LOXL2 or LOXL3 in epithelial cells induces an EMT process,
      supporting their implication in tumor progression. The biological importance of
      LOXL2 is further supported by RNA interference of LOXL2 in Snail-expressing
      metastatic carcinoma cells, which led to a strong decrease of tumor growth
      associated to increased apoptosis and reduced expression of mesenchymal and
      invasive/angiogenic markers. Taken together, these results establish a direct
      link between LOXL2 and Snail in carcinoma progression.

PMID- 16096639
TI  - Taz1, Rap1 and Rif1 act both interdependently and independently to maintain
      telomeres.
AB  - Telomere protection and maintenance are accomplished through the coordinated
      actions of telomere-specific DNA binding proteins and their interacting partners.
      The fission yeast ortholog of human TRF1/2, Taz1, binds telomeric DNA and
      regulates numerous aspects of telomere function. Here, we ask which aspects of
      Taz1 function are mediated through its interacting proteins, Rap1 and Rif1. We
      demonstrate that rap1+ deletion phenocopies some, but not all, aspects of
      taz1Delta telomere dysfunction, while Rif1 exhibits a very different functional
      spectrum. Rap1 acts in a Taz1-dependent pathway to prevent chromosome end fusions
      and regulate telomeric 3' overhang formation, while Rif1 is dispensable for these
      functions. Telomerase inhibition by Taz1 is mediated by two separate pathways,
      one involving Rap1 and the other involving Rif1. In contrast, Taz1 is uniquely
      required to prevent chromosomal entanglements and missegregation at cold
      temperatures. Strikingly, while rap1+ deletion exacerbates the cold sensitivity
      of taz1Delta cells, rif1+ deletion restores full viability. Thus, Rap1 and Rif1
      are each required for a subset of the functions of Taz1, but each acquires Taz1
      independent functions in its absence. Furthermore, Taz1 can function
      independently of its known binding partners.

PMID- 16096641
TI  - A plant RNA virus suppresses RNA silencing through viral RNA replication.
AB  - RNA interference (RNAi) is a post-transcriptional gene-regulatory mechanism that
      operates in many eukaryotes. RNAi is induced by double-stranded RNA (dsRNA) and
      is mainly involved in defence against transposons and viruses. To counteract
      RNAi, viruses have RNAi suppressors. Here we show a novel mechanism of RNAi
      suppression by a plant virus Red clover necrotic mosaic virus (RCNMV). To
      suppress RNAi, RCNMV needs multiple viral components, which include viral RNAs
      and putative RNA replicase proteins. A close relationship between the RNA
      elements required for negative-strand RNA synthesis and RNAi suppression suggests
      a strong link between the viral RNA replication machinery and the RNAi machinery.
      In a transient assay, RCNMV interferes with the accumulation of small-interfering
      RNA (siRNAs) in RNAi induced by a hairpin dsRNA and it also interferes with
      microRNA (miRNA) biogenesis. An Arabidopsis dcl1 mutant showed reduced
      susceptibility to RCNMV infection. Based on these results, we propose a model in
      which, to replicate, RCNMV deprives the RNAi machinery of Dicer-like enzymes that
      are involved in both siRNA and miRNA biogenesis.

PMID- 16096640
TI  - Rap1 prevents telomere fusions by nonhomologous end joining.
AB  - Telomeres protect chromosomes from end-to-end fusions. In yeast Saccharomyces
      cerevisiae, the protein Rap1 directly binds telomeric DNA. Here, we use a new
      conditional allele of RAP1 and show that Rap1 loss results in frequent fusions
      between telomeres. Analysis of the fusion point with restriction enzymes
      indicates that fusions occur between telomeres of near wild-type length. Telomere
      fusions are not observed in cells lacking factors required for nonhomologous end
      joining (NHEJ), including Lig4 (ligase IV), KU and the Mre11 complex. SAE2 and
      TEL1 do not affect the frequency of fusions. Together, these results show that
      Rap1 is essential to block NHEJ between telomeres. Since the presence of Rap1 at
      telomeres has been conserved through evolution, the establishment of NHEJ
      suppression by Rap1 could be universal.

PMID- 16096642
TI  - Transforming activity of Fbxo7 is mediated specifically through regulation of
      cyclin D/cdk6.
AB  - D cyclins (D1, D2 and D3) and their catalytic subunits (cyclin-dependent kinases
      cdk4 and cdk6) have a facilitating, but nonessential, role in cell cycle entry.
      Tissue-specific functions for D-type cyclins and cdks have been reported;
      however, the biochemical properties of these kinases are indistinguishable. We
      report that an F box protein, Fbxo7, interacted with cellular and viral D cyclins
      and distinguished among the cdks that bind D-type cyclins, specifically binding
      cdk6, in vitro and in vivo. Fbxo7 specifically regulated D cyclin/cdk6 complexes:
      Fbxo7 knockdown decreased cdk6 association with cyclin and its overexpression
      increased D cyclin/cdk6 activity and E2F activity. Fbxo7 interacted with p27, but
      its enhancement of cyclin D/cdk6 activity was p21/p27 independent. Fbxo7
      overexpression transformed murine fibroblasts, rendering them tumorigenic in
      athymic nude mice. Transformed phenotypes were dependent on cdk6, as knockdown of
      cdk6 reversed them. Fbxo7 was highly expressed in epithelial tumors, but not in
      normal tissues, suggesting that it may have a proto-oncogenic role in human
      cancers.

PMID- 16096643
TI  - 14-3-3eta is a novel regulator of parkin ubiquitin ligase.
AB  - Mutation of the parkin gene, which encodes an E3 ubiquitin-protein ligase, is the
      major cause of autosomal recessive juvenile parkinsonism (ARJP). Although various
      substrates for parkin have been identified, the mechanisms that regulate the
      ubiquitin ligase activity of parkin are poorly understood. Here we report that 14
      3-3eta, a chaperone-like protein present abundantly in neurons, could bind to
      parkin and negatively regulate its ubiquitin ligase activity. Furthermore, 14-3
      3eta could bind to the linker region of parkin but not parkin with ARJP-causing
      R42P, K161N, and T240R mutations. Intriguingly, alpha-synuclein (alpha-SN),
      another familial Parkinson's disease (PD) gene product, abrogated the 14-3-3eta
      induced suppression of parkin activity. alpha-SN could bind tightly to 14-3-3eta
      and consequently sequester it from the parkin-14-3-3eta complex. PD-causing A30P
      and A53T mutants of alpha-SN could not bind 14-3-3eta, and failed to activate
      parkin. Our findings indicate that 14-3-3eta is a regulator that functionally
      links parkin and alpha-SN. The alpha-SN-positive and 14-3-3eta-negative control
      of parkin activity sheds new light on the pathophysiological roles of parkin.

PMID- 16096644
TI  - Prion generation in vitro: amyloid of Ure2p is infectious.
AB  - [URE3] is a prion (infectious protein) of the Ure2 protein of yeast. In vitro,
      Ure2p can form amyloid filaments, but direct evidence that these filaments
      constitute the infectious form is still missing. Here we demonstrate that
      recombinant Ure2p converted into amyloid can infect yeast cells lacking the
      prion. Infection produced a variety of [URE3] variants. Extracts of [URE3]
      strains, as well as amyloid of Ure2p formed in an extract-primed reaction could
      transmit to uninfected cells the [URE3] variant present in the cells from which
      the extracts were made. Infectivity and determinant of [URE3] variants resided
      within the N-terminal 65 amino acids of Ure2p. Notably, we could show that
      amyloid filaments of recombinant Ure2p are nearly as infectious per mass of Ure2p
      as extracts of [URE3] strains. Sizing experiments indicated that infectious
      particles in vitro and in vivo were >20 nm in diameter, suggesting that they were
      amyloid filaments and not smaller oligomeric structures. Our data indicate that
      there is no substantial difference between filaments formed in vivo and in vitro.

PMID- 16096645
TI  - Acetylation of HIV-1 integrase by p300 regulates viral integration.
AB  - Integration of HIV-1 into the human genome, which is catalyzed by the viral
      protein integrase (IN), preferentially occurs near transcriptionally active
      genes. Here we show that p300, a cellular acetyltransferase that regulates
      chromatin conformation through the acetylation of histones, also acetylates IN
      and controls its activity. We have found that p300 directly binds IN both in
      vitro and in the cells, as also specifically demonstrated by fluorescence
      resonance energy transfer technique analysis. This interaction results in the
      acetylation of three specific lysines (K264, K266, K273) in the carboxy-terminus
      of IN, a region that is required for DNA binding. Acetylation increases IN
      affinity to DNA, and promotes the DNA strand transfer activity of the protein. In
      the context of the viral replication cycle, point mutations in the IN acetylation
      sites abolish virus replication by specifically impairing its integration
      capacity. This is the first demonstration that HIV-1 IN activity is specifically
      regulated by post-translational modification.

PMID- 16096646
TI  - Chromosomal protein HMGN1 enhances the acetylation of lysine 14 in histone H3.
AB  - The acetylation levels of lysine residues in nucleosomes, which are determined by
      the opposing activities of histone acetyltransferases (HATs) and deacetylases,
      play an important role in regulating chromatin-related processes, including
      transcription. We report that HMGN1, a nucleosomal binding protein that reduces
      the compaction of the chromatin fiber, increases the levels of acetylation of K14
      in H3. The levels of H3K14ac in Hmgn1-/- cells are lower than in Hmgn1+/+ cells.
      Induced expression of wild-type HMGN1, but not of a mutant that does not bind to
      chromatin, in Hmgn1-/- cells elevates the levels of H3K14ac. In vivo, HMGN1
      elevates the levels of H3K14ac by enhancing the action of HAT. In vitro, HMGN1
      enhances the ability of PCAF to acetylate nucleosomal, but not free, H3. Thus,
      HMGN1 modulates the levels of H3K14ac by binding to chromatin. We suggest that
      HMGN1, and perhaps similar architectural proteins, modulates the levels of
      acetylation in chromatin by altering the equilibrium generated by the opposing
      enzymatic activities that continuously modify and de-modify the histone tails in
      nucleosomes.

PMID- 16096647
TI  - The U11/U12 snRNP 65K protein acts as a molecular bridge, binding the U12 snRNA
      and U11-59K protein.
AB  - U11 and U12 interact cooperatively with the 5' splice site and branch site of pre
      mRNA as a stable preformed di-snRNP complex, thereby bridging the 5' and 3' ends
      of the intron within the U12-dependent prespliceosome. To identify proteins
      contributing to di-snRNP formation and intron bridging, we investigated protein
      protein and protein-RNA interactions between components of the U11/U12 snRNP. We
      demonstrate that the U11/U12-65K protein possesses dual binding activity,
      interacting directly with U12 snRNA via its C-terminal RRM and the U11-associated
      59K protein via its N-terminal half. We provide evidence that, in contrast to the
      previously published U12 snRNA secondary structure model, the 3' half of U12
      forms an extended stem-loop with a highly conserved seven-nucleotide loop and
      that the latter serves as the 65K binding site. Addition of an oligonucleotide
      comprising the 65K binding site to an in vitro splicing reaction inhibited U12
      dependent, but not U2-dependent, pre-mRNA splicing. Taken together, these data
      suggest that U11/U12-65K and U11-59K contribute to di-snRNP formation and intron
      bridging in the minor prespliceosome.

PMID- 16096648
TI  - AAA ATPases regulate membrane association of yeast oxysterol binding proteins and
      sterol metabolism.
AB  - The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p,
      which have been implicated in regulating intracellular lipid and vesicular
      transport. Here, we show that both Osh6p and Osh7p interact with Vps4p, a member
      of the AAA (ATPases associated with a variety of cellular activities) family. The
      coiled-coil domain of Osh7p was found to interact with Vps4p in a yeast two
      hybrid screen and the interaction between Osh7p and Vps4p appears to be regulated
      by ergosterol. Deletion of VPS4 induced a dramatic increase in the membrane
      associated pools of Osh6p and Osh7p and also caused a decrease in sterol
      esterification, which was suppressed by overexpression of OSH7. Lastly,
      overexpression of the coiled-coil domain of Osh7p (Osh7pCC) resulted in a
      multivesicular body sorting defect, suggesting a dominant negative role of
      Osh7pCC possibly through inhibiting Vps4p function. Our data suggest that a
      common mechanism may exist for AAA proteins to regulate the membrane association
      of yeast OSBP proteins and that these two protein families may function together
      to control subcellular lipid transport.

PMID- 16096649
TI  - Mll fusions generated by Cre-loxP-mediated de novo translocations can induce
      lineage reassignment in tumorigenesis.
AB  - Chromosomal translocations are primary events in tumorigenesis. Those involving
      the mixed lineage leukaemia (MLL) gene are found in various guises and it is
      unclear whether MLL fusions can affect haematopoietic differentiation. We have
      used a model in which chromosomal translocations are generated in mice de novo by
      Cre-loxP-mediated recombination (translocator mice) to compare the functionally
      relevant haematopoietic cell contexts for Mll fusions, namely pluripotent stem
      cells, semicommitted progenitors or committed cells. Translocations between Mll
      and Enl or Af9 cause myeloid neoplasias, initiating in pluripotent stem cells or
      multipotent myeloid progenitors. However, while Mll-Enl translocations can also
      cause leukaemia from T-cell progenitors, no tumours arose with Mll-Af9
      translocations in the T-cell compartment. Furthermore, Mll-Enl translocations in
      T-cell progenitors can cause lineage reassignment into myeloid tumours.
      Therefore, a permissive cellular environment is required for oncogenicity of Mll
      associated translocations and Mll fusions can influence haematopoietic lineage
      commitment.

PMID- 16096651
TI  - Small interfering RNA expression vector targeting hypoxia-inducible factor 1
      alpha inhibits tumor growth in hepatobiliary and pancreatic cancers.
AB  - Hepatobiliary and pancreatic carcinomas are hypovascular tumors that can
      proliferate under hypoxic conditions. Recent reports have demonstrated that
      hypoxia-inducible factor 1 alpha (HIF1alpha) plays an important role in the
      survival of these cancers. Given these findings, the inhibition of the HIF1alpha
      pathway might prove to be a powerful tool in the treatment of these cancers. To
      inhibit HIF1alpha expression, we used small interference RNA (siRNA) expression
      vectors in this study. The transient transfection of siRNA expression vectors
      significantly reduced both HIF1alpha mRNA levels (13% of control) and protein
      levels (41% of control) and significantly inhibited the growth of cancer cell
      lines (P<0.05). VEGF, Glut1, and aldorase A expressions were also significantly
      reduced by transfection with these vectors (P<0.05), and we found that these
      vectors induced apoptosis but not cell cycle arrest. In a subcutaneous tumor
      model using nude mice, transfected MIA PaCa-2 cells, stably expressing siRNAs,
      barely formed tumors compared to control (P<0.05). This study thus demonstrates
      the usefulness of siRNA expression vector in targeting HIF1alpha and points to a
      potential clinical role in the treatment of pancreatic and hepatobiliary
      carcinomas.

PMID- 16096650
TI  - The carcinoma-specific epithelial glycoprotein-2 promoter controls efficient and
      selective gene expression in an adenoviral context.
AB  - Adenoviral vectors are widely used in cancer gene therapy. After systemic
      administration however, the majority of the virus homes to the liver and the
      expressed transgene may cause hepatotoxicity. To restrict transgene expression to
      tumor cells, tumor- or tissue-specific promoters are utilized. The tumor antigen
      epithelial glycoprotein-2 (EGP-2), also known as Ep-CAM, is expressed in many
      cancers from different epithelial origins. In this study, the EGP-2 promoter was
      shown to restrict the expression of luciferase and thymidine kinase in an
      adenoviral context in different cell lines. In vivo, the EGP-2 promoter mediated
      efficient expression of luciferase in tumors but showed a 3-log lower activity in
      liver tissue when compared with the cytomegalovirus (CMV) promoter. Similarly,
      the EGP-2 promoter mediated specific cell killing after ganciclovir treatment in
      EGP-2-positive cells. Moreover, in vivo, this treatment regiment did not cause
      any rise in the liver enzymes aspartate aminotransferase (ASAT) and alanine
      aminotransferase (ALAT), demonstrating absence of liver toxicity. In contrast,
      CMV-mediated expression of thymidine kinase in combination with ganciclovir
      treatment resulted in high ASAT and ALAT values. This study demonstrates the
      value of the EGP-2 promoter to restrict transgene expression to a broad range of
      tumor types, thereby preventing liver toxicity.

PMID- 16096652
TI  - Peritoneal cancer treatment with CYP2B1 transfected, microencapsulated cells and
      ifosfamide.
AB  - The prognosis of peritoneal spread from gastrointestinal cancer and subsequent
      malignant ascites is poor, and current medical treatments available are mostly
      ineffective. Targeted chemotherapy with intraperitoneal prodrug activation may be
      a beneficial new approach. L293 cells were genetically modified to express the
      cytochrome P450 enzyme 2B1 under the control of a cytomegalovirus immediate early
      promoter. This CYP2B1 enzyme converts ifosfamide to its active cytotoxic
      compounds. The cells are encapsulated in a cellulose sulfate formulation
      (Capcell). Adult Balb/c mice were inoculated intraperitoneally with 1 x 10(6)
      colon 26 cancer cells, previously transfected with GFP to emit a stable green
      fluorescence, by injection into the left lower abdominal quadrant. Two or five
      day's later animals were randomly subjected to either i.p. treatment with
      ifosfamide alone or ifosfamide combined with microencapsulated CYP2B1-expressing
      cells. Peritoneal tumor volume and tumor viability were assessed 10 days after
      tumor inoculation by means of fluorescence microscopy, spectroscopy and
      histology. Early i.p. treatment with ifosfamide and CYP2B1 cells resulted in a
      complete response. Treatment starting on day 5 and single-drug treatment with
      ifosfamide resulted in a partial response. These results suggest that targeted
      i.p. chemotherapy using a combination of a prodrug and its converting enzyme may
      be a successful treatment strategy for peritoneal spread from colorectal cancer.

PMID- 16096653
TI  - p53 deficiency rescues apoptosis and differentiation of multiple cell types in
      zebrafish flathead mutants deficient for zygotic DNA polymerase delta1.
AB  - Cell culture work has identified the tumor suppressor p53 as a component of the S
      phase checkpoint control system, while in vivo studies of this role of p53 in
      whole-vertebrate systems were limited. Here, we describe zebrafish mutants in the
      DNA polymerase delta catalytic subunit 1, based on the positional cloning of the
      flathead (fla) gene. fla mutants display specific defects in late proliferative
      zones, such as eyes, brain and cartilaginous elements of the visceral head
      skeleton, where cells display compromised DNA replication, followed by apoptosis,
      and partial or complete loss of affected tissues. Antisense-mediated knockdown of
      p53 in fla mutants leads to a striking rescue of all phenotypic traits, including
      completion of replication, survival of cells, and normal differentiation and
      tissue formation. This indicates that under replication-compromised conditions,
      the p53 branch of the S-phase checkpoint is responsible for eliminating stalled
      cells that, given more time, would have otherwise finished their normal
      developmental program.

PMID- 16096654
TI  - Twist is substrate for caspase cleavage and proteasome-mediated degradation.
AB  - Twist is a member of the basic helix-loop-helix family of transcription factors.
      An aberrant Twist expression has been found in diverse types of cancer, including
      sarcomas, carcinomas and lymphomas, supporting a role for Twist in tumor
      progression. Twist is known to be essential for mesodermal development. However,
      since a prolonged Twist expression results in a block of muscle, cartilage and
      bone differentiation, Twist has to be excluded from somites during late
      embryogenesis for terminal differentiation to occur. This implies that Twist
      expression must be target of a tight control. Here we provide evidence that Twist
      undergoes post-transcriptional regulation. Twist is substrate for cleavage by
      caspases during apoptosis and its cleavage results in ubiquitin-mediated
      proteasome degradation. Our findings suggest that Twist post-transcriptional
      regulation may play an important role in tissue determination and raise the
      possibility that alterations in the protein turnover may account for Twist
      overexpression observed in tumors.

PMID- 16096655
TI  - Reliability and validity of the partial coherence interferometry for measurement
      of ocular axial length in children.
AB  - PURPOSE: To assess the validity and repeatability of partial coherence
      interferometry (IOLMaster) and A-scan ultrasound measurement of axial length (AL)
      in children. METHODS: A prospective comparison of AL measurement made by the
      IOLMaster optical instrument (Carl Zeiss) and ultrasound A-scan (Alcon) was
      performed. A total of 20 children (11 male, nine female) were recruited into the
      study; the mean age of the sample was 11.4 years (range 6.2-15.8). Inclusion
      criteria comprised individuals <16 years, with no ocular pathology and no
      previous eye operations or allergy to topical anaesthetics. All measurements were
      performed by a single examiner. RESULTS: Data on validity show that, on average,
      a small measurement difference existed between these groups with the IOLMaster
      being 0.017 mm greater than A-scan ultrasonography. The 95% confidence interval
      for this difference encompasses zero, demonstrating that no significant
      systematic bias exists between the two-measurement techniques. Overall, IOLMaster
      reliability exceeded that of A-scan. This is evidenced primarily by the spread of
      the paired test-retest difference for A-scan compared to IOLMaster. The mean test
      retest difference for A-scan was considerably larger than IOLMaster at 0.042 and
      0.004 mm, respectively. CONCLUSION: The results show that IOLMaster was more
      accurate and reproducible than the contact ultrasonographic technique when used
      in children. Such results indicate that IOLMaster may be a useful tool in studies
      of eye growth and refractive development in children.

PMID- 16096656
TI  - Low-dose intraocular triamcinolone injection for intractable macular oedema and
      inflammation in patients with uveitis.
AB  - AIMS: To evaluate the efficacy and safety of low-dose (2 mg in 0.05 ml)
      intraocular triamcinolone injection for patients with uveitis-related cystoid
      macular oedema and/or intractable intraocular inflammation. PATIENTS AND METHODS:
      Retrospective clinical case series. RESULTS: Cystoid macular oedema was
      eliminated in 24/30 eyes (80%). Intractable intraocular inflammation was
      eliminated in 4/8 eyes (50%). Snellen visual acuity was improved by two lines or
      more after 14/36 injections (38.9%). Intraocular pressure rose to above 21 mmHg
      after 8/36 injections (22%). There were no major complications. CONCLUSIONS: Low
      dose (2 mg in 0.05 ml) intraocular triamcinolone acetonide injection is safe and
      effective for the management of refractory uveitic macular oedema. Its usefulness
      in controlling inflammation alone is questionable.

PMID- 16096657
TI  - Diagnosis of pre-existing posterior capsule defect in traumatic white mature
      cataract with intact anterior capsule.

PMID- 16096658
TI  - Evaluating an impression cytology grading system (IC score) in patients with dry
      eye syndrome.
AB  - PURPOSE: To evaluate the IC score, a newly developed grading system for the
      morphological alterations of the ocular surface as a diagnostic tool in relation
      to type and severity of dry eye disease. METHODS: Impression cytological
      specimens of 309 patients with simple dry eye (S-DE), 50 patients with Sjogren's
      syndrome and dry eye (SS-DE), and 39 patients with connective tissue disease and
      dry eye (CTD-DE) were examined. In all, 10 different morphological parameters
      were judged with points (IC subscores) and summarized to the IC score. IC score
      and subscores were correlated to tear function test results and with each other.
      RESULTS: SS-DE patients had the highest IC scores and IC subscores. IC scores and
      IC subscores correlated significantly with the fluorescein staining of the cornea
      in all three patient groups. They were correlated to the rose bengal score in SS
      DE and S-DE patients. The analysis of the IC subscores showed that there are
      significant correlations between most of the morphological alterations
      investigated. This underlines the importance of each parameter for the summarized
      IC score. CONCLUSION: The IC score provides detailed information about the
      morphological alterations of the bulbar conjunctiva. It has proven to be useful
      for the differentiation of dry eye diseases and might help in the investigation
      of the pathogenesis of these diseases as well as for follow-up and therapy
      control.

PMID- 16096659
TI  - Endogeneous endophthalmitis caused by Sporobolomyces salmonicolor.

PMID- 16096661
TI  - A case of occult giant cell arteritis presenting with bilateral cotton wool
      spots.

PMID- 16096662
TI  - Intravitreal triamcinolone as a primary therapy in diabetic macular oedema.

PMID- 16096663
TI  - Long-term visual prognosis of infantile-onset high myopia.
AB  - PURPOSE: To investigate the clinical course and changes of refractive status in
      infantile-onset myopic children who received fully corrected glasses and to
      determine their visual prognosis. METHODS: In all, 57 children with infantile
      onset high myopia (spherical equivalent over -5.0 D prior to the age of 5 years)
      were included in this study. All children received initial full-correction
      glasses at the mean age of 3.52 years. The cycloplegic refraction, axial length,
      and the best-corrected visual acuity were collected every 6 months. The mean
      follow-up time was 9.36 years. RESULTS: We noted that the tendency toward
      progression or regression of myopia appeared to be related to the degree of
      refractive error. Lower grades of high myopia (-5.0 to -7.75 D) showed a greater
      tendency to progress than those of the highest initial myopic refraction level (<
      or = -11.0 D). While the latter group exhibited a more-substantial regression
      rate than those cases of the lower initial refraction level. About 80% of
      infantile-onset high myopes demonstrated a final best-corrected vision of greater
      than 20/40, with 37% of children revealing a best-corrected vision level even
      better than 20/25. CONCLUSION: Clinical course of infantile high myopia is
      different to school myopia. Usually, higher degree of high myopia showed a stable
      state of myopia, or even possible regression, whereas the lower grades of high
      myopia revealed a strong tendency to progress.

PMID- 16096664
TI  - A prospective study on trypan blue capsule staining under air vs under
      viscoelastic.
AB  - AIM: To compare the safety and effectiveness of trypan blue capsule staining
      under air vs under viscoelastic. METHODS: A total of 52 consecutive patients
      planned for phacoemulsification of white mature cataract were randomly assigned
      to trypan blue staining under air or under viscoelastic. Perioperative changes in
      best-corrected visual acuity (BCVA), central corneal thickness (CCT), and
      endothelial cell density (ECD) were compared between the two groups. The
      differences in operating and phacoemulsification times, staining pattern, and
      complications between the two groups were also recorded. RESULTS:
      Phacoemulsification of white mature cataract was performed in 50 (96%) eyes. The
      median preoperative BCVA was hand movement. No significant differences in the
      baseline characteristics were found between the two groups. At 3 months after
      phacoemulsification, the median BCVA improved to 0.8. The mean CCT returned to
      preoperative level by 1 month postoperatively and the mean ECD loss was 11.9% 3
      months postoperatively. No significant differences in median BCVA, mean
      phacoemulsification and operation times, mean CCT, and mean ECD were found
      between the two groups. CONCLUSIONS: Trypan blue staining of the anterior lens
      capsule under air or under viscoelastic were similarly effective and safe methods
      for the phacoemulsification of white mature cataract.

PMID- 16096665
TI  - Staining of filtering bleb with trypan blue during phacoemulsification.

PMID- 16096666
TI  - Precise proteomic identification using mass spectrometry coupled with stable
      isotope labeling.
AB  - Stable isotope labeling (SIL) can assist mass spectrometry to improve its
      specificity and throughput in protein identification, de novo sequencing, and
      characterization of post translational modifications. This Education article
      summarizes the unique characteristics of stable isotope-assisted mass
      spectrometry for accurate protein identification without requirements for
      ultrahigh mass accuracy. Some applications are discussed here to demonstrate the
      general experimental procedures, data interpretation, and the improvements in
      accuracy and throughput compared to the use of mass spectrometry alone.

PMID- 16096667
TI  - Exploring the electrocatalytic sites of carbon nanotubes for NADH detection: an
      edge plane pyrolytic graphite electrode study.
AB  - The electrocatalytic properties of multi-walled carbon nanotube modified
      electrodes toward the oxidation of NADH are critically evaluated. Carbon nanotube
      modified electrodes are examined and compared with boron-doped diamond and glassy
      carbon electrodes, and most importantly, edge plane and basal pyrolytic graphite
      electrodes. It is found that CNT modified electrodes are no more reactive than
      edge plane pyrolytic graphite electrodes with the comparison with edge plane and
      basal plane pyrolytic graphite electrodes allowing the electroactive sites for
      the electrochemical oxidation of NADH to be unambiguously determined as due to
      edge plane sites. Using these highly reactive edge plane sites, edge plane
      pyrolytic graphite electrodes are examined with cyclic voltammetry and
      amperometry for the electroanalytical determination of NADH. It is demonstrated
      that a detection limit of 5 microM is possible with cyclic voltammetry or 0.3
      microM using amperometry suggesting that edge plane pyrolytic graphite electrodes
      can conveniently replace carbon nanotube modified glassy carbon electrodes for
      biosensing applications with the relative advantages of reactivity, cost and
      simplicity of preparation. We advocate the routine use of edge plane and basal
      plane pyrolytic graphite electrodes in studies utilising carbon nanotubes
      particularly if 'electrocatalytic' properties are claimed for the latter.

PMID- 16096668
TI  - A DNA assay protocol in a lab-on-valve meso-fluidic system with detection by
      laser-induced fluorescence.
AB  - An automatic protocol for in-situ assay of dsDNA is presented by employing a
      micro-sequential injection lab-on-valve meso-fluidic system, which facilitates
      precise fluidic handling at the 0.1-10 microl level. Sub-nano-liter to a few
      micro-liters of DNA sample and ethidium bromide (EB) solutions were introduced
      into the meso-fluidic system, where EB binding onto DNA takes place and an
      intercalated DNA-EB adduct was formed, which was afterwards excited in the flow
      cell of the LOV by a 473 nm laser beam, and the emitted fluorescence was
      monitored in-situvia optical fibers. The experimental variables, i.e., pH of the
      buffer solution, the concentration and volume of EB solution, the reaction time
      and the fluid flow rates, were investigated. By loading 600 nl sample and 1.0
      microl EB solution, a linear calibration graph was obtained within 0.03-3.0
      microg ml(-1)(dsDNA), and a detection limit (3sigma) of 0.009 microg ml(-1) was
      achieved, along with a sampling frequency of 60 h(-1) and a precision of 1.9% at
      the 1.0 microg ml(-1) level. The detection limit was further improved to 0.006
      microg ml(-1) by increasing the sample volume to 2.0 microl. Plasmid DNA in E.
      Coli extraction and lambda-DNA/Hind III in four synthetic samples were assayed by
      using this procedure. For the plasmid DNA, a good agreement with the documented
      UV method was obtained, while spiking recoveries for the synthetic samples were
      95.6-103.4%.

PMID- 16096669
TI  - Robotic sequential analysis of a library of metalloporphyrins as electrocatalysts
      for voltammetric nitric oxide sensors.
AB  - A library of 83 metalloporphyrins with varying substitution pattern at the meso
      position of the porphyrins and different central metal ions in the core region
      has been synthesized in small quantities using a parallel synthesis strategy. By
      means of a specially designed electrochemical robotic device integrating a 96
      well microtitre plate and an easily movable assembly of working, counter and
      reference electrodes, the different porphyrins were automatically applied in
      sequence to an in-well electrochemical preparation and testing of NO sensors.
      Screening the entire compound collection suggested initial considerations
      concerning the influence of varied functionalities of the metalloporphyrins on
      their electrocatalytic properties for the oxidation of NO and helped to identify
      the quality of the investigated catalyst candidates. As compared to manually
      performed quality tests, the proposed strategy of automation has advantages in
      convenience, rapidity and especially reproducibility avoiding any inaccuracies
      introduced by manually performing all steps of the complex sensor formation and
      testing sequence.

PMID- 16096670
TI  - Development of a micro dual beam fluorometric detector specific for microchip
      analysis of benzo[a]pyrene and benzo[k]fluoranthene in diesel exhaust particulate
      samples.
AB  - We developed a device and some systems for detecting benzo[a]pyrene (B[a]P) and
      benzo[k]fluoranthene (B[k]F). The device uses a UV light-emitting diode that
      emits light with a wavelength of 370 nm and a violet laser diode that emits light
      with a wavelength of 395 nm as excitation light sources. The detection method is
      based on the following observation: characteristic fluorescence is emitted from
      both B[a]P and B[k]F, with intensities up to 10 times greater than those from 22
      other polycyclic aromatic hydrocarbons (PAHs). The excitation and emission
      wavelengths for fluorescence from B[a]P and B[k]F are 370 and 429 nm, and 395 and
      429 nm, respectively. Further, we calculated their concentrations in diesel
      exhaust particles by means of two calibration curves determined using a mixture
      of 24 PAHs. The detection limits of the proposed device with a microchip are 5.58
      microg L(-1) for B[a]P and 6.03 microg L(-1) for B[k]F. We applied this method to
      analyze B[a]P or B[k]F contained in three types of diesel exhaust particles, and
      the results agreed well with those obtained by liquid chromatography.

PMID- 16096671
TI  - Analytical chemistry of synthetic routes to psychoactive tryptamines. Part III.
      Characterisation of the Speeter and Anthony route to N,N-dialkylated tryptamines
      using CI-IT-MS-MS.
AB  - Twelve symmetrically and 13 asymmetrically N,N-disubstituted glyoxalylamide
      precursors and their corresponding tryptamine derivatives have been characterised
      by gas chromatography low-pressure chemical ionisation ion trap tandem mass
      spectrometry (CI-IT-MS-MS) with internal (in situ) ionisation using methanol as
      the chemical ionisation reagent. Mass spectral differences and similarities
      between the investigated compounds are discussed and put into context with
      previous investigations. In tryptamines the formation of [CH2=N+R2R3] iminium
      ions after beta-cleavage appears to be the dominating process. Dissociation of
      the protonated molecule into [3-vinylindole]+ for example, appears to be a minor
      pathway when compared with electrospray triple quadrupole tandem mass
      spectrometry (ESI-TQ-MS-MS) where this ion transition was found to be of
      distinctive importance. CI-IT-MS-MS is also found to enable the differentiation
      between most isomeric derivatives studied.

PMID- 16096672
TI  - Single-step analysis of low abundance phosphoamino acids via on-line sample
      preconcentration with chemical derivatization by capillary electrophoresis.
AB  - New strategies for rapid, sensitive and high-throughput analysis of low abundance
      metabolites in biological samples are required for future metabolomic research.
      In this report, a direct method for sub-micromolar analyses of phosphoamino acids
      was developed using on-line sample preconcentration with 9
      fluorenylmethyloxycarbonyl chloride (FMOC) derivatization by capillary
      electrophoresis (CE) and UV detection. Analyte focusing by dynamic pH junction
      and FMOC labeling efficiency were influenced by several experimental factors
      including buffer pH, ionic strength, sample injection length and FMOC
      concentration. About a 200-fold enhancement in concentration sensitivity was
      achieved under optimal conditions relative to conventional off-line
      derivatization, as reflected by a detection limit (S/N approximately 3) of 0.1
      microM. In-capillary sample preconcentration with chemical labeling by CE offers
      a unique single-step analytical platform for high-throughput screening of low
      abundance metabolites without intrinsic chromophores.

PMID- 16096673
TI  - Two-stage application of the optimised uncertainty method: a practical
      assessment.
AB  - Uncertainty estimates from routine sampling and analytical procedures can be
      assessed as being fit for purpose using the optimised uncertainty (OU) method.
      The OU method recommends an optimal level of uncertainty that should be reached
      in order to minimise the expected financial loss, given a misclassification of a
      batch as a result of the uncertainty. Sampling theory can used as a predictive
      tool when a change in sampling uncertainty is recommended by the OU method. The
      OU methodology has been applied iteratively for the first time using a case study
      of wholesale butter and the determination of five quality indicators (moisture,
      fat, solids-not-fat (SNF), peroxide value (PV) and free fatty acid (FFA)). The
      sampling uncertainty (s(samp)) was found to be sub-optimal for moisture and PV
      determination, for 3-fold composite samples. A revised sampling protocol was
      devised using Gy's sampling theory. It was predicted that an increase in sample
      mass would reduce the sampling uncertainty to the optimal level, resulting in a
      saving in expectation of loss of over pounds 2000 per 20 tonne batch, when
      compared to current methods. Application of the optimal protocol did not however,
      achieve the desired reduction in s(samp) due to limitations in sampling theory.
      The OU methodology proved to be a useful tool in identifying broad weaknesses
      within a routine protocol and assessing fitness for purpose. However, the
      successful routine application of sampling theory, as part of the optimisation
      process, requires substantial prior knowledge of the sampling target.

PMID- 16096674
TI  - Benford's Law and the screening of analytical data: the case of pollutant
      concentrations in ambient air.
AB  - The need to ensure the robustness of very large data sets produced by analytical
      measurement processes is increasing. This requires data screening techniques that
      can identify formatting or transcription errors in large data sets, that have
      undergone multiple data-handling and manipulation procedures. The empirical
      observation that the digits 1 to 9 are not equally likely to appear as the
      initial digit in multi-digit numbers is known as Benford's Law, and may provide a
      solution to this requirement. Several sets of data pertaining to the measured
      concentrations of pollutants in ambient air in the UK in 2004 have been analysed
      for their initial digit frequencies in order to assess the potential for the use
      of Benford's Law as a data screening, and authenticity-checking, tool for these
      types of analytical data sets. Benford's Law has been shown to be a robust top
      level data screening tool provided that the numerical range of the data set being
      considered is four orders of magnitude or greater. It has been shown that small
      changes in the deviation of a data set from Benford's Law may indicate the
      introduction of errors during data processing. In this way, Benford's Law
      provides a sensitive technique for identifying data mishandling in large data
      sets.

PMID- 16096675
TI  - Determination of histamine in wines with an on-line pre-column flow
      derivatization system coupled to high performance liquid chromatography.
AB  - A new rapid and sensitive high performance liquid chromatography (HPLC) method
      for determining histamine in red wine samples, based on continuous flow
      derivatization with 1,2-naphthoquinone-4-sulfonate (NQS), is proposed. In this
      system, samples are derivatized on-line in a three-channel flow manifold for
      reagent, buffer and sample. The reaction takes place in a PTFE coil heated at 80
      degrees C and with a residence time of 2.9 min. The reaction mixture is injected
      directly into the chromatographic system, where the histamine derivative is
      separated from other aminated compounds present in the wine matrix in less than
      ten minutes. The HPLC procedure involves a C18 column, a binary gradient of 2%
      acetic acid-methanol as a mobile phase, and UV detection at 305 nm. Analytical
      parameters of the method are evaluated using red wine samples. The linear range
      is up to 66.7 mg L(-1) (r = 0.9999), the precision (RSD) is 3%, the detection
      limit is 0.22 mg L(-1), and the average histamine recovery is 101.5% +/- 6.7%.
      Commercial red wines from different Spanish regions are analyzed with the
      proposed method.

PMID- 16096676
TI  - Evaluation of complex spectral-pH three-way arrays by modified bilinear least
      squares: determination of four different dyes in interfering systems.
AB  - This article reports on the first application of a modified version of the
      bilinear least-squares model to absorbance-pH second-order data recorded for
      complex samples. The latter are composed of fruit drink powders, where four
      different analytes and additional background components occur. The analytes are
      the common juice colorants tartrazine, yellow sunset, allura red and indigo
      carmine. The data have been measured after generating a double pH gradient within
      a flow injection system. The selected chemometric methodology adequately exploits
      the second-order advantage, needed to take into account the background
      interferents present in real samples. Due to severe spectral overlapping between
      the acid and basic forms of each of the colorants in the working pH range, other
      second-order multivariate calibration methods such as parallel factor analysis
      and multivariate curve resolution-alternating least-squares could not be
      successfully applied to the presently studied samples. Recoveries of 94.8, 104.7,
      109.3 and 105.3% were obtained for yellow sunset, indigo carmine, allura red and
      tartrazine respectively in the real test samples.

PMID- 16096677
TI  - Determination of perfluorooctanoic acid (PFOA) extractable from the surface of
      commercial cookware under simulated cooking conditions by LC/MS/MS.
AB  - Salts of pentadecafluorooctanoic acid (PFOA) are polymerization aids used in the
      manufacture of fluoropolymers; one of the applications of fluoropolymers is the
      coating of metal cookware products. A method was developed to determine if PFOA
      might be present in and extracted from the surface of commercial frying pans
      coated with a DuPont fluoropolymer under simulated cooking conditions. Commercial
      grade cookware was obtained, then extracted with water and ethanol/water mixtures
      at 100 and 125 degrees C, and the resulting extracts were analyzed by liquid
      chromatography tandem mass spectrometry (LC/MS/MS). Detection and quantification
      limits as low as 100 pg cm(-2) were demonstrated. None of the fluoropolymer
      treated cookware samples analyzed showed detectable levels of PFOA when extracted
      under simulated cooking conditions.

PMID- 16096678
TI  - Boron-doped diamond microdisc arrays: electrochemical characterisation and their
      use as a substrate for the production of microelectrode arrays of diverse metals
      (Ag, Au, Cu)via electrodeposition.
AB  - A novel boron-doped diamond (BDD) microelectrode array is characterised with
      electrochemical and atomic force microscopic techniques. The array consists of 40
      micron-diameter sized BDD discs which are separated by 250 microns from their
      nearest neighbour in a hexagonal arrangement. The conducting discs can be
      electroplated to produce arrays of copper, silver or gold for analytical purposes
      in addition to operating as an array of BDD-microelectrodes. Proof-of-concept is
      shown for four separate examples; a gold plated array for arsenic detection, a
      copper plated array for nitrate analysis, a silver plated array for hydrogen
      peroxide monitoring and last, cathodic stripping voltammetry for lead at the bare
      BDD-array.

PMID- 16096679
TI  - Sensitive detection of salbutamol using europium-enhanced fluorescence with
      trioctylphosphine oxide (TOPO) as coligand.
AB  - In this work a simple and sensitive fluorimetric method for determination of
      salbutamol (4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl) phenol)
      using an Eu enhanced signal was developed. The employed methodology is based on
      the formation of a ternary complex formed with Eu, salbutamol and
      trioctylphosphine oxide (TOPO). Intermolecular transfer of energy from the
      excited organic molecule to the lanthanide followed by lanthanide emission is
      responsible for excitation of the lanthanide ion in complex solutions and
      fluorescent enhancement. The luminescence properties of the ternary complex
      formed with TOPO and optimum formation conditions were investigated. The
      calibration curve is linear in the range between 6.92-180 microg l(-1) of
      salbutamol. The detection limit was 2.31 microg l(-1). Common excipients for
      these formulations were not found to interfere. A proposed method for the assay
      in commercial aerosols and nebulizer solutions containing salbutamol was applied
      with very good precision.

PMID- 16096680
TI  - In vitro selection of high temperature Zn(2+)-dependent DNAzymes.
AB  - In vitro selection of Zn(2+)-dependent RNA-cleaving DNAzymes with activity at 90
      degrees C has yielded a diverse spool of selected sequences. The RNA cleavage
      efficiency was found in all cases to be specific for Zn(2+) over Pb(2+), Ca(2+),
      Cd(2+), Co(2+), Hg(2+), and Mg(2+). The Zn(2+)-dependent activity assay of the
      most active sequence showed that the DNAzyme possesses an apparent Zn(2+)-binding
      dissociation constant of 234 muM and that its activity increases with increasing
      temperatures from 50-90 degrees C. A fit of the Arrhenius plot data gave E(a) =
      15.3 kcal mol(-1). Surprisingly, the selected Zn(2+)-dependent DNAzymes showed
      only a modest (approximately 3-fold) activity enhancement over the background
      rate of cleavage of random sequences containing a single embedded ribonucleotide
      within an otherwise DNA oligonucleotide. The result is attributable to the
      ability of DNA to sustain cleavage activity at high temperature with minimal
      secondary structure when Zn(2+) is present. Since this effect is highly specific
      for Zn(2+), this metal ion may play a special role in molecular evolution of
      nucleic acids at high temperature.

PMID- 16096681
TI  - Evolutionary robustness of an optimal phenotype: re-evolution of lysis in a
      bacteriophage deleted for its lysin gene.
AB  - Optimality models are frequently used to create expectations about phenotypic
      evolution based on the fittest possible phenotype. However, they often ignore
      genetic details, which could confound these expectations. We experimentally
      analyzed the ability of organisms to evolve towards an optimum in an
      experimentally tractable system, lysis time in bacteriophage T7. T7 lysozyme
      helps lyse the host cell by degrading its cell wall at the end of infection,
      allowing viral escape to infect new hosts. Artificial deletion of lysozyme
      greatly reduced fitness and delayed lysis, but after evolution both phenotypes
      approached wild-type values. Phage with a lysis-deficient lysozyme evolved
      similarly. Several mutations were involved in adaptation, but most of the change
      in lysis timing and fitness increase was mediated by changes in gene 16, an
      internal virion protein not formerly considered to play a role in lysis. Its
      muralytic domain, which normally aids genome entry through the cell wall, evolved
      to cause phage release. Theoretical models suggest there is an optimal lysis
      time, and lysis more rapid or delayed than this optimum decreases fitness.
      Artificially constructed lines with very rapid lysis had lower fitness than wild
      type T7, in accordance with the model. However, while a slow-lysing line also had
      lower fitness than wild-type, this low fitness resulted at least partly from
      genetic details that violated model assumptions.

PMID- 16096682
TI  - Signaling pathways in activity-dependent fiber type plasticity in adult skeletal
      muscle.
AB  - Adult fast- and slow-twitch skeletal muscle fibers exhibit characteristic
      differences in functional properties due to differences in the isoforms and
      quantities of expression of most muscle proteins. However, these differences may
      be reversed by chronic electrical stimulation of denervated muscle with the
      pattern typical of the other fiber type. Here, we review three possible signaling
      pathways that may contribute to fast to slow fiber type transformation. The first
      pathway involves cytosolic activation of the Ca(2+) sensitive posphatase
      calcineurin (CaN) due to elevated cytosolic [Ca(2+)], resulting in
      dephosphorylation of cytoplasmic NFATc, translocation of dephosphorylated NFATc
      from cytoplasm into the nucleus and activation of slow fiber gene expression by
      NFATc in the nucleus. The second pathway involves elevated intranuclear [Ca(2+)]
      causing the activation of nuclear calmodulin dependent protein kinase, which
      phosphorylates HDAC within the nucleus and thereby permits nuclear efflux of
      HDAC, thus decreasing the HDAC suppression of MEF2 activation of slow fiber gene
      expression. The third possible pathway involves nuclear entry of CaN,
      dephosphorylation of intranuclear MEF2 and consequent increased activation of
      slow fiber type gene expression by dephosphorylated MEF2. Evidence for the first
      two pathways from our studies on adult fast twitch skeletal muscle fibers is
      briefly reviewed.

PMID- 16096683
TI  - Novel sarco(endo)plasmic reticulum proteins and calcium homeostasis in striated
      muscles.
AB  - The impact of calcium signaling on many cellular functions is reflected by the
      tight regulation of the intracellular Ca(2+) concentration that is ensured by
      diverse pumps, channels, transporters and Ca(2+) binding proteins. In this
      review, we present recently identified novel sarco(endo)plasmic reticulum
      proteins that may have a potential involvement in the regulation of Ca(2+)
      homeostasis in striated muscles.

PMID- 16096685
TI  - Arcanobacterium pyogenes: molecular pathogenesis of an animal opportunist.
AB  - Arcanobacterium pyogenes is a commensal and an opportunistic pathogen of
      economically important livestock, causing diseases as diverse as mastitis, liver
      abscessation and pneumonia. This organism possesses a number of virulence factors
      that contribute to its pathogenic potential. A. pyogenes expresses a cholesterol
      dependent cytolysin, pyolysin, which is a haemolysin and is cytolytic for immune
      cells, including macrophages. Expression of pyolysin is required for virulence
      and this molecule is the most promising vaccine candidate identified to date. A.
      pyogenes also possesses a number of adherence mechanisms, including two
      neuraminidases, the action of which are required for full adhesion to epithelial
      cells, and several extracellular matrix-binding proteins, including a collagen
      binding protein, which may be required for adhesion to collagen-rich tissue. A.
      pyogenes also expresses fimbriae, which are similar to the type 2 fimbriae of
      Actinomyces naeslundii, and forms biofilms. However, the role of these factors in
      the pathogenesis of A. pyogenes infections remains to be elucidated. A. pyogenes
      also invades and survives within epithelial cells and can survive within J774A.1
      macrophages for up to 72 h, suggesting an important role for A. pyogenes
      interaction with host cells during pathogenesis. The two component regulatory
      system, PloSR, up-regulates pyolysin expression and biofilm formation but down
      regulates expression of proteases, suggesting that it may act as a global
      regulator of A. pyogenes virulence. A. pyogenes is a versatile pathogen, with an
      arsenal of virulence determinants. However, most aspects of the pathogenesis of
      infection caused by this important opportunistic pathogen remain poorly
      characterized.

PMID- 16096686
TI  - Acute oral intragastric pathogenicity and toxicity in mice of Paecilomyces
      fumosoroseus isolated from whiteflies.
AB  - Paecilomyces fumosoroseus, monospore culture EH-506/3, isolated in Mexico from
      Bemisia tabaci whitefly was tested for acute oral intragastric pathogenicity and
      toxicity in CD-1 mice. Animals were inoculated by gavage with only one dose
      (10(8) conidia/animal) of viable (72 mice), heat-killed (24 mice) fungus and
      compared to 18 control mice. Clinical observations were done daily; mycological
      and histological tests were performed during necropsies at days 3, 10, 17, and 21
      after the inoculation. No mice were clinically ill or died. At the end of the
      study, their mean weight corresponded to healthy adults. Positive fungal cultures
      of feces were obtained only 24 h after inoculation. Positive cultures were found
      in 15 out of 360 organs (liver, spleen, kidney, brain, lung) in 12 of 72 mice
      inoculated with viable conidia. Gross pathology exhibited splenomegaly and liver
      paleness in mice inoculated with viable and heat-killed fungus. Non-germinated
      conidia were observed in studied organs, without any pathological tissue
      reaction, suggesting no mycological or histopathological evidence of fungal
      multiplication. The fungus was able to persist, but did not cause permanent
      damage to the host. This study supports the non-pathogenic/toxic status of P.
      fumosoroseus EH-506/3 when administered intragastrically in mice.

PMID- 16096687
TI  - A newly constructed primer pair for the PCR amplification, cloning and sequencing
      of the flagellin (flaA) gene from isolatesof urease-negative Campylobacter lari.
AB  - A newly constructed primer pair (lari-Af/lari-Ar) designed to generate a product
      of the flagellin (flaA) gene for urease-negative Campylobacter lari produced a
      PCR amplicon of about 1700 bp for 16 isolates from 7 seagulls, 5 humans, 3 food
      animals and one mussel in Japan and Northern Ireland. Nucleotide sequencing and
      alignments of the flaA amplicons from these isolates demonstrated that the
      deduced amino acid sequences of the possible open reading frame were 564-572
      amino acid residues in length with calculated molecular weights of 58,804 to
      59,463. The deduced amino acid sequence similarity analysis strongly suggested
      that the ORF of the flaA from the 16 isolates showed 70-75% sequence similarities
      to those of Campylobacter jejuni isolates. The approximate Mr of the flagellin
      purified from some of the isolates of urease-negative C. lari was estimated to
      range from 59.6 to 61.8 kDa. Thus, flagellin from the isolates of urease-negative
      C. lari was shown for the first time to have a molecular size similar to those of
      C. jejuni and Campylobacter coli isolates, but to be different from the shorter
      flaA and smaller flagellin of urease-positive thermophilic Campylobacter (UPTC)
      isolates. Flagellins from C. lari spp., consisting of the two representative taxa
      of urease-negative C. lari and UPTC, thus show genotypic and phenotypic
      diversity.

PMID- 16096688
TI  - New species and a new combination in the Hyphopichia and Yarrowia yeast clades.
AB  - Three new species of Candida and a new combination in the genus Hyphopichia are
      proposed from phylogenetic analysis of nucleotide divergence in domains D1/D2 of
      the large subunit (26S) rDNA. The new taxa and their type strains are the
      following: Candida bentonensis sp. nov. (NRRL YB-2364, CBS 9994), Candida
      hispaniensis sp. nov. (NRRL Y-5580, CBS 9996), Candida pseudorhagii sp. nov.
      (NRRL YB-2076, CBS 9998) and Hyphopichia heimii comb. nov. (NRRL Y-7502, CBS
      6139), basionym Pichia heimii Pignal. Phylogenetic analysis placed C.
      pseudorhagii and H. heimii in the Hyphopichia clade whereas C. bentonensis and C.
      hispaniensis are members of the Yarrowia clade.

PMID- 16096689
TI  - Origin of (-)-geosmin on grapes: on the complementary action of two fungi,
      botrytis cinerea and penicillium expansum.
AB  - One of the consequences of rot on grapes is the development of volatile compounds
      giving fungal, mouldy or earthy odours. Among these compounds, (-)-geosmin (trans
      1,10-dimethyl-trans-9-decalol), a powerful aromatic compound with an earthy smell
      is a persistent defect in grape juice and wines made with at least partially
      rotten grapes. A microbiota analysis of rotten grapes containing (-)-geosmin was
      carried out on sites from four French regions from 1999 to 2002, to clarify the
      involvement in geosmin appearance of Streptomyces spp. and Penicillium spp., two
      types of microorganisms present on grape, that are known for their ability to
      produce geosmin. In earthy grapes, Botrytis cinerea was largely present.
      Different species of Streptomyces were also isolated, but their pH sensitivity
      was an extremely limiting parameter for their development on grape juice, grapes
      or stem, and consequently for their potentiality to generate geosmin in the
      vineyard. Penicillium expansum, producing geosmin on a model medium, was
      omnipresent. Penicillium carneum, which is also a geosmin producer, was
      represented by a single colony during the 4 years of this study. P. expansum
      alone was able to produce geosmin on a model medium but not on grapes. However,
      after 7 days' pre-culture of some B. cinerea strains on grape juice, this juice
      became favourable to geosmin production by P. expansum. We demonstrated the
      necessary and complementary action of B. cinerea and P. expansum in geosmin
      production in grape juice and in crushed grape berries.

PMID- 16096690
TI  - Evolutionary relationships among Aspergillus terreus isolates and their
      relatives.
AB  - Aspergillus terreus is a ubiquitous fungus in our environment. It is an
      opportunistic human pathogen and economically important as the main producer of
      lovastatin, a cholesterol lowering drug. Our aim was to examine the genetic
      variability of A. terreus and closely related species using molecular and
      analytical techniques. Lovastatin production was examined by HPLC. Lovastatin was
      produced by seven isolates belonging to the species A. terreus. RAPD analyses
      were carried out using 25 different random primers. Neighbor-joining analysis of
      RAPD data (120 characters) resulted in clustering of the A. terreus isolates into
      distinct groups. Some correlation was observed between lovastatin producing
      abilities of the isolates and their position on the dendrogram based on RAPD
      profiles. The internal transcribed spacer region and the 5.8S rRNA gene of A.
      terreus and related isolates was also sequenced. Phylogenetic analysis of
      sequence data let us classify the isolates into different clades which mostly
      correspond to the species Aspergillus terreus, Aspergillus flavipes, Aspergillus
      niveus, Aspergillus carneus and Aspergillus janus/A. janus var. brevis.
      Aspergillus allahabadii, A. terreus var. aureus and A. niveus var. indicus
      belonged to the A. niveus clade, while an Aspergillus isolate previously
      classified as A. niveus was most closely related to A. flavipes isolates.
      Aspergillus anthodesmis formed a distinct branch on the tree. Although it was
      previously suggested based on 28S rDNA sequence data that Aspergillus section
      Terrei should include A. carneus and A. niveus isolates, phylogenetic analysis of
      ITS sequences indicate that A. flavipes isolates are more closely related to A.
      terreus than A. carneus isolates. Our data suggest that sections Terrei and
      Flavipedes should be merged. However, further loci should be analysed to draw
      more definite conclusions.

PMID- 16096691
TI  - Rapid phenotypic characterization of Vibrio isolates by pyrolysis metastable atom
      bombardment mass spectrometry.
AB  - Pyrolysis mass spectrometry was investigated for rapid characterization of food
      borne bacterial pathogens. Nine isolates of Vibrio parahaemolyticus and one
      isolate each of Vibrio fluvialis, Vibrio hollisae, and Vibrio vulnificus were
      analyzed. Pyrolysis mass spectra, generated via an alternative ionization method,
      metastable atom bombardment, were subject to principal component-discriminant
      analysis. The spectral patterns were used to distinguish Vibrio isolates
      differing in species, serotype and expression of the thermostable direct
      hemolysin gene. The patterns of similarity and dissimilarity amongst spectra in
      the Vibrio test set generally reflected those associated with species, serotype
      or hemolysin-producing genes, though the combined influence of these and other
      variables in the multi-dimensional data did not produce a simple clustering with
      respect to any one of these characteristics. These results suggested that with
      enough examples to model the most common combinations, the method should be able
      to characterize Vibrio isolates according to their phenotypic characteristics.
      Pyrolysis-mass spectrometry with metastable atom bombardment and pattern
      recognition appeared suitable for rapid infraspecific comparison of Vibrio
      isolates. This integrated analytical, pattern-recognition system should be
      examined further for potential utility in clinical and public health diagnostic
      contexts.

PMID- 16096692
TI  - Screening of cry2 genes in Bacillus thuringiensis isolates from Argentina.
AB  - A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method for identification of cry2 genes from Bacillus thuringiensis (Bt) was
      established. Strains from different sources of Argentina were analyzed to study
      the distribution of cry2 genes. The results showed that cry2Aa/cry2Ab profile was
      the most abundant irrespective of source and represented 56 of 59 Bt isolates
      (94.9%). Three different cry2 profiles were found in this collection, one of
      which was novel.

PMID- 16096693
TI  - Evaluation of microbial strains for linoleic acid hydroxylation and
      reclassification of strain ALA2.
AB  - In previous studies, a new microbial strain ALA2 was isolated which produced many
      new products from linoleic acid [Gardner H.W., Hou C.T., Weisleder D. and Brown
      W. 2000. Lipids 35: 1055-1060; Hou C.T. 1998. 12,13,17-Trihydroxy-9(Z)
      Octodecenoic acid and derivatives and microbial isolate for production of the
      acid. US Patent No. 5, 852, 196]. Strain ALA2 was preliminary identified as
      Clavibacter sp. based on its physiological and fatty acid profiles. To determine
      if strain ALA2 is the optimal strain for industrial applications, other related
      strains were screened for their abilities to convert linoleic acids. Two strains
      from Clavibacter and 20 type strains from the phylogenetically related genus
      Microbacterium were studied. Surprisingly, all of these strains tested showed
      very little or no activity in converting linoleic acid. On reexamination of the
      identification of strain ALA2, the sequence of the 16S ribosomal RNA gene of ALA2
      was found to be 99% identical to that of Bacillus megaterium and the strain was
      also found to have 76.3% DNA homology to the B. megaterium type strain.
      Therefore, strain ALA2 is now reclassified as B. megaterium. Screening of 56
      strains of B megaterium strains showed that many of them were able to produce
      reasonable amounts of hydroxyl fatty acids from linoleic acid, although strain
      ALA2 possessed the greatest activity.

PMID- 16096694
TI  - BOX-PCR is an adequate tool for typing Aeromonas spp.
AB  - PCR-based methods of fingerprinting take advantage of the presence of repetitive
      sequences that are interspersed throughout the genome of diverse bacterial
      species. They include the repetitive extragenic palindromic (REP) sequence, the
      enterobacterial repetitive intergenic consensus sequence (ERIC) and the 154-bp
      BOX element. The combination of the three methods is used for fine discrimination
      of strains and is designated as rep-polymerase chain reaction (PCR). REP-PCR and
      ERIC-PCR have been shown to be useful for typing Aeromonas strains. To our
      knowledge, rep-PCR fingerprinting method using the BOXA1R primer has never been
      tested on aeromonads. In this study, the BOX-PCR fingerprinting technique was
      evaluated for the discrimination of strains of some Aeromonas species. All
      strains were typeable and the majority showed unique banding patterns. Four
      strains from culture collections were used to investigate the reproducibility of
      the method. According to our results, BOX-PCR fingerprinting is applicable for
      typing of Aeromonas strains and can be considered as a useful complementary tool
      for epidemiological studies of members of this genus.

PMID- 16096695
TI  - Regulation of the pyrimidine biosynthetic pathway in Pseudomonas mucidolens.
AB  - Control of pyrimidine biosynthesis was examined in Pseudomonas mucidolens ATCC
      4685 and the five de novo pyrimidine biosynthetic enzyme activities unique to
      this pathway were influenced by pyrimidine supplementation in cells grown on
      glucose or succinate as a carbon source. When uracil was supplemented to glucose
      grown ATCC 4685 cells, activities of four de novo enzymes were depressed which
      indicated possible repression of enzyme synthesis. To learn whether the pathway
      was repressible, pyrimidine limitation experiments were conducted using an
      orotate phosphoribosyltransferase (pyrE) mutant strain identified in this study.
      Compared to excess uracil growth conditions for the glucose-grown mutant strain
      cells, pyrimidine limitation of this strain caused aspartate transcarbamoylase,
      dihydroorotase and dihydroorotate dehydrogenase activities to increase by more
      than 3-fold while OMP decarboxylase activity increased by 2.7-fold. The syntheses
      of the de novo enzymes appeared to be regulated by pyrimidines. At the level of
      enzyme activity, aspartate transcarbamoylase activity in P. mucidolens ATCC 4685
      was subject to inhibition at saturating substrate concentrations.
      Transcarbamoylase activity was strongly inhibited by UTP, ADP, ATP, GTP and
      pyrophosphate.

PMID- 16096696
TI  - Synchronization of rotating helices by hydrodynamic interactions.
AB  - Some types of bacteria use rotating helical flagella to swim. The motion of such
      organisms takes place in the regime of low Reynolds numbers where viscous effects
      dominate and where the dynamics is governed by hydrodynamic interactions.
      Typically, rotating flagella form bundles, which means that their rotation is
      synchronized. The aim of this study is to investigate whether hydrodynamic
      interactions can be at the origin of such a bundling and synchronization. We
      consider two stiff helices that are modelled by rigidly connected beads,
      neglecting any elastic deformations. They are driven by constant and equal
      torques, and they are fixed in space by anchoring their terminal beads in
      harmonic traps. We observe that, for finite trap strength, hydrodynamic
      interactions do indeed synchronize the helix rotations. The speed of phase
      synchronization decreases with increasing trap stiffness. In the limit of
      infinite trap stiffness, the speed is zero and the helices do not synchronize.

PMID- 16096697
TI  - Needs and quality of life among patients with schizophrenia in five European
      centres: what is the impact of global functioning scores?
AB  - BACKGROUND: Global assessment of functioning, quality of life (QOL) and patient
      needs have been discussed as inter-related domains important for care planning
      and outcome assessment in care for the severely mentally ill. The study was
      conducted to investigate relationships of functioning level, subjective QOL and
      unmet needs in a cross-sectional study of 404 patients with schizophrenia
      spectrum disorders in five European centres with a focus on the patient group
      with low function scores. METHODS: Patient groups with low, medium and high
      function scores were compared with regard to subjective QOL and unmet needs. QOL
      variability was assessed in subgroups according to function scores. Regression
      analyses were used to examine the impact of illness-related and other unmet
      patient needs on QOL. The influence of individual needs in the low and
      medium/high function score subgroup was compared. RESULTS: QOL increased and
      unmet needs decreased from the low to high function score subgroup. There was
      greater QOL variability in patients with low function scores compared to those
      with medium and high function scores, with some low-function score patients
      having relatively high QOL. In the low function score subgroup, both illness
      related and other needs had an impact on QOL, whereas non-illness needs
      influenced QOL in medium and high function score patients. CONCLUSION: Scores of
      functioning level, in people with schizophrenia spectrum disorders, are related
      to QOL in a complex way, and types of unmet need impinge on the relationship. In
      order to improve QOL in people with low function scores, both illness-related and
      other needs should be met.

PMID- 16096698
TI  - Mood disorders and urban/rural settings: comparisons between two French regions.
AB  - BACKGROUND: A review of the main large-scale mental health surveys does not give
      full support to the idea of urbanicity as a risk factor in mood disorders. Lack
      of agreement between findings can be attributed, at least in part, to
      heterogeneous operationalisation of urbanicity, as different ways to define urban
      and rural areas are likely to lead to different morbidity rates and to have an
      effect on the respective weight of other risk factors. METHODS: A total of 2,638
      subjects sampled from two French regions (Basse-Normandie and Ile-de-France) were
      interviewed using face-to-face parts of the Composite International Diagnostic
      Interview covering demographic and certain life event questions. Urbanicity was
      defined according to (1) official index based on population density or (2) type
      of dwelling. Participation rates were 85 and 79%. RESULTS: When gender, age,
      marital status and certain early life events, such as being placed in an
      institution, as well as events concerning close family members are entered into a
      logistic regression, the urbanicity association with DSM-IV MDE and especially
      severe forms disappeared. This finding tends to support the theory that what
      happens to individuals is more relevant to depression than the place where they
      live. CONCLUSION: It may be wiser to rely on social indicators than on a
      rural/urban component for planning for mental health care in the various areas;
      this remark should not prevent to evaluate the topographic situations of the
      diverse settings to take them into account to provide appropriate resources.

PMID- 16096699
TI  - Changing patterns of suicide in a poor, rural county over the 20th century: a
      comparison with national trends.
AB  - Rural suicide rates have been shown to be disproportionately high in several
      countries. This study compares suicide rates in Cornwall with the rest of England
      and Wales over a 90-year period (1911-2001). Age and sex standardised mortality
      ratios were calculated for suicide and undetermined death for Cornwall
      standardised to England and Wales. From 1911 until the start of the Second World
      War, suicide rates were lower in Cornwall than England and Wales. Since the 1960s
      suicide rates in Cornwall have risen significantly above England and Wales. We
      have shown that the suicide rate in a poor, rural area has increased
      disproportionately compared to England and Wales over the last 35 years. This
      change has occurred in both sexes. Prior to this period the suicide rate was
      lower or about the same as that in England and Wales.

PMID- 16096700
TI  - Psychosocial risk factors to major depression after childbirth.
AB  - BACKGROUND: Risk factors to postnatal depression (PND) have generally been
      identified in well-defined homogenous samples of primiparous women. There is a
      need for studies to assess risk factors in a heterogeneous sample of women. AIM:
      This study is aimed to identify psychosocial risk factors to postnatal
      depression. METHOD: Subjects underwent a baseline assessment within 2 days of
      childbirth and completed postal questionnaires at 6, 12, 18 and 24 weeks
      postpartum. Postnatal depression was defined as scoring above 12 on the Edinburgh
      Postnatal Depression Scale on two occasions and meeting criteria for major
      depression using the Structured Clinical Interview for DSM-III-R. RESULTS: Four
      hundred and twenty-five women with a mean age of 26.9 years participated in the
      study. Forty-two women were considered to be cases of postnatal depression. A
      significantly increased risk for postnatal depression was associated with (a)
      being 16 years old or younger, (b) a past history of psychiatric illness, (c)
      experiencing one or more life events, (d) marital dissatisfaction, (e)
      experiencing unsatisfactory social support, (f) a vulnerable personality and (g)
      having a baby of the nondesired sex. CONCLUSION: This study confirmed that
      psychosocial risk factors, predominantly in the areas of social support and
      personality style, are closely associated with postnatal depression.

PMID- 16096701
TI  - Antioxidant effectiveness of organically and non-organically grown red oranges in
      cell culture systems.
AB  - BACKGROUND: Consumers consider plant food products from organic origin healthier
      than the corresponding conventional plant foods. Clear experimental evidence
      supporting this assumption is still lacking. AIM OF THE STUDY: To determine if
      the organic red oranges have a higher phyto-chemical content (i. e., phenolics,
      anthocyanins and ascorbic acid), total antioxidant activity and in vitro
      bioactivity, in terms of protective effect against oxidative damage at cellular
      level, than nonorganic red oranges. METHODS: Total phenolics were measured using
      the Folin Ciocalteau assay, while total anthocyanins and ascorbic acid levels
      were determined by spectrophotometric and HPLC analysis, respectively. In
      addition, the total antioxidant activity of red orange extracts was measured by
      the ABTS(*+) test. The ability of red orange extracts to counteract conjugated
      diene containing lipids and free radical production in cultured rat
      cardiomyocytes and differentiated Caco-2 cells, respectively, was assessed.
      RESULTS: Organic oranges had significantly higher total phenolics, total
      anthocyanins and ascorbic acid levels than the corresponding non-organic oranges
      (all p < 0.05). Moreover, the organic orange extracts had a higher total
      antioxidant activity than non-organic orange extracts (p < 0.05). In addition,
      our results indicate that red oranges have a strong capacity of inhibiting the
      production of conjugated diene containing lipids and free radicals in rat
      cardiomyocytes and differentiated Caco-2 cells, respectively. Statistically
      higher levels of antioxidant activity in both cell models were found in
      organically grown oranges as compared to those produced by integrated agriculture
      practice. CONCLUSIONS: Our results clearly show that organic red oranges have a
      higher phytochemical content (i. e., phenolics, anthocyanins and ascorbic acid),
      total antioxidant activity and bioactivity than integrated red oranges. Further
      studies are needed to confirm whether the organic agriculture practice is likely
      to increase the antioxidant activity of other varieties of fruits and vegetables.

PMID- 16096702
TI  - Phase I and pharmacokinetic study of docetaxel, irinotecan, and celecoxib in
      patients with advanced non-small cell lung cancer.
AB  - PURPOSE: We studied the toxicities, potential pharmacokinetic interactions, and
      preliminary antitumor activity of the combination of docetaxel and irinotecan
      with celecoxib, a selective cyclooxygenase-2 inhibitor. PATIENTS AND METHODS:
      Eligible patients had advanced non-small lung cancer (NSCLC) with measurable
      disease, good performance status, and adequate end organ function. Docetaxel and
      irinotecan were administered intravenously on days 1 and 8, every 21 days, and
      their doses were escalated on successive patient cohorts at three dose levels:
      30/50, 30/60, and 35/60 (doses in mg/m2). Celecoxib was administered at a
      starting dose of 400 mg orally twice daily without interruption, beginning on day
      2 of cycle 1. Pharmacokinetic studies were performed on day 1 of cycle 1 and day
      1 of cycle 2. RESULTS: Seventeen patients with advanced NSCLC were enrolled and
      collectively received 78 cycles of therapy. Diarrhea was the most common
      toxicity; it was noted in 13 patients (76%). Dose-limiting toxicities occurred at
      dose level 1 (myocardial infarction in a patient with multiple coronary artery
      disease risk factors) and dose level 3 (grade 4 neutropenia with fatal
      urosepsis). Other major toxicities were: grade 3 neutropenia (2 patients); grade
      3/4 diarrhea (3/1); grade 3 nausea (2); grade 2 rash (1); and grade 3 pneumonitis
      (1). The maximum tolerated dose was at dose level 3, i.e., docetaxel 35 mg/m2 and
      irinotecan 60 mg/m2 on days 1 and 8, plus celecoxib 400 mg twice daily, repeated
      every 21 days. Five of 15 evaluable patients achieved an objective response. The
      pharmacokinetics of docetaxel were not altered by celecoxib. However, we observed
      an 18% increase in the average elimination clearance of irinotecan coincident
      with the addition of celecoxib. CONCLUSIONS: The addition of celecoxib to
      docetaxel and irinotecan was generally well tolerated but unpredictable fatal
      toxicity occurred. Diarrhea was the most common toxicity. Antitumor activity was
      promising. The alteration of irinotecan pharmacokinetic parameters observed may
      not be clinically relevant.

PMID- 16096703
TI  - Suppression of primary breast, colon, gastric and bladder cancers cell growth in
      vitro by CKBM, a natural product.
AB  - CKBM is a product composed of natural ingredients and had been shown to possess
      certain anti-cancer effects in vitro and in vivo. The aim of the present study is
      to analyze the chemosensitivity in the treatment of primary colon, breast,
      gastric and bladder cancer cells by CKBM. A total of 77 patients with cancers of
      breast, colon, stomach or bladder were included in the present study. Primary
      cancer cells were isolated from the surgical removed tumors and treated with
      various dosages of CKBM for 5 days. ATP is then extracted and measured by
      luminescence assay. CKBM treatment inhibited primary colon, breast, gastric and
      bladder cancer growth dose-dependently. The IC values were smaller from tumor
      cells at early stages, when compared with the ones at later stages. The present
      study strongly indicated that CKBM exerted cytotoxic effect on primary cancer
      cells.

PMID- 16096704
TI  - Gemcitabine and vinorelbine (GV) versus cisplatin, gemcitabine and vinorelbine
      (CGV) as first-line treatment in advanced non small cell lung cancer: results of
      a prospective randomized phase II study.
AB  - The objective of this study was to assess whether adding cisplatin to
      gemcitabine/vinorelbine combination improves the clinical outcome in patients
      with non-small-cell lung cancer (NSCLC). Chemotherapy-naive patients with
      advanced NSCLC; age < or = 75 years: Karnofsky performance status > or = 60%, and
      with adequate hematological, renal and hepatic function, were randomized into 2
      treatment groups to receive Gemcitabine 1250 mg/m2 + vinorelbine 30 mg/m2 (GV
      group), or cisplatin 50 mg/m2 + gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2
      (CGV group). All drugs were administered on days 1 and 8 every three weeks: From
      September 1999 to March 2003, 114 patients were enrolled. No statistically
      significant difference was observed in GV vs CGV group in objective response (37
      versus 47%, respectively; P = 0.5), median time to progression (5 versus 5.8
      months; P = 0.6), overall survival (9 versus 10 months; P = 0.9) and 1-year
      survival (26 versus 28%; P = 0.9). Conversely, toxicities were significantly
      higher for CGV, including grade 3-4 neutropenia (24 versus 45%); neutropenic
      fever (4 versus 14%, including one toxic death); grade 3-4 thrombocytopenia (2
      versus 14%); and grade 3-4 emesis (2 versus 14%). Our results suggest that the
      combination of gemcitabine and vinorelbine is less toxic than three-drug
      combination with cisplatin while showing similar efficacy.

PMID- 16096706
TI  - Molecular epidemiology of chicken anemia virus in Nigeria.
AB  - Between February 2002 and May 2004, chicken anemia virus (CAV) was detected by
      PCR in organ samples from 14 flocks of poultry farms in Lagos, Ogun and Oyo
      States in Southwestern Nigeria. The farms reported low (<5%) to high mortalities
      (up to 100%) with various lesions at necropsy. The complete VP1 gene of 30 of
      these positive strains was sequenced. Strains that diverged by up to 4.4% on a
      nucleotide level differed only by up to 2.5% at the amino acid level (7 aa) as a
      result of clustered silent mutations. No amino acid substitutions specific for
      Nigerian strains were observed. Some birds had a CAV mixed infection. Genetic
      clustering of the VP1 gene did not correlate with differences in flock mortality
      but the co-infection of CAV with IBDV may be particularly lethal. This first
      molecular epidemiological study of CAV in Africa shows that the Nigerian strains
      cluster with viruses from very diverse geographic origins and were almost as
      diverse (4.4%) as all other strains combined (5.8%).

PMID- 16096705
TI  - The diversity of Banana streak virus isolates in Uganda.
AB  - In a study of the variation among isolates of Banana streak virus (BSV) in
      Uganda, 140 sequences were obtained from 49 samples by PCR across the conserved
      reverse transcriptase/RNaseH region of the genome. Pairwise comparison of these
      sequences suggested that they represented 15 different species and phylogenetic
      analyses showed that all species fell into three major clades based on 28%
      sequence difference. In addition to the Ugandan sequences, clade I also contained
      BSV species that are known as both integrated sequences and episomal viruses;
      clade II also contained integrated BSV sequences but which have not previously
      been identified as episomal viruses. Clade III comprised of Sugarcane bacilliform
      virus isolates and Ugandan BSV sequences and for which there is no evidence of
      integration. The possible reasons for the extraordinary levels of virus sequence
      variation and the potential origins and epidemiology of these viruses causing
      banana streak disease are discussed.

PMID- 16096707
TI  - Genome structure and complete sequence of genomic RNA of Daphne virus S.
AB  - The complete genomic nucleotide sequence and structure of Daphne virus S (DVS), a
      daphne-infecting member of the genus Carlavirus, were determined. The genome of
      DVS was 8,739 nucleotides long, excluding the poly (A) tails. The genome of DVS
      contained six open reading frames coding for proteins of Mr 227 kDa (viral
      replicase), 25 kDa, 11 kDa and 7 kDa (triple gene block TGB) proteins 1, 2 and
      3), 35 kDa (coat protein; CP), and 12 kDa from the 5' to 3' ends; respectively.
      This is the typical genome structure of members of the genus Carlavirus. Overall
      amino acid sequence similarities for the six ORFs of DVS were from 58.5% to 13.2%
      to those of the other carlaviruses. The 227 kDa replicase of DVS shared 45.5
      39.2% amino acid similarities to that of 8 other known carlaviruses. Results from
      phylogenetic analyses of viral replicases and CPs demonstrated that DVS is a
      close relative of Helenium virus S and Chrysanthemum virus B. A total of 13
      isolates of DVS shared 100-95.9% identities for the amino acid level and 99.5
      81.0% identities for the nucleotide level. This is the first report of the
      complete genome sequence and structure of DVS and supports the conclusion that
      DVS is a typical species of the genus Carlavirus.

PMID- 16096708
TI  - Conservation of the N-terminus of some phage tail proteins.
AB  - To study the interaction between lipopolysaccharide and protein, a comparative
      approach was employed using seven Salmonella enterica serovar Typhimurium typing
      phages as the protein model systems. This interaction has been studied in detail
      in the Salmonella enterica serovar Typhimurium phage P22 system and involves only
      the viral tailspike protein. Similarity between these phages and phage P22 was
      monitored in this Report by assaying restriction endonuclease digestions, capsid
      size, reactivity to the P22 tailspike protein monoclonal antibody, mAb92, which
      reacts with the N-terminus of the P22 tail protein and the ability to produce a
      PCR fragment using primers made to the ends of the P22 tailspike gene. The data
      indicate that tailspike similarity exists between most of these phages and a
      scheme reclassifying them is presented and that the N-terminus of the P22
      tailspike protein may be a motif for many phage systems and may serve as a aid in
      the taxonomy of phages. The data suggest a classification scheme in which the N
      terminus of some tailspike proteins (head-binding region in some tail proteins)
      may play a critical element role in the classification of Salmonella viruses.

PMID- 16096709
TI  - Dengue 2 genotypes in the state of Oaxaca, Mexico.
AB  - To genetically characterize dengue 2 (DEN-2) viruses in Oaxaca, Mexico, the C
      protein, and a portion of the prM protein genes of 8 isolates from the 2001 DEN
      epidemic were sequenced. The sequences were compared to those of prototype DEN-2
      viruses from various parts of the world. Phylogenetic analysis suggested that the
      2001 isolates of DEN-2 were of the American/Asian genotype and were most similar
      to the Jamaica and Venezuelan isolates MARA3, LARD1996 and LARD1910. Molecular
      analyses confirmed the origin of the isolates. This study indicates that DEN-2
      strains of American/Asian genotype probably from Southeast Asian are circulating
      in Oaxaca.

PMID- 16096710
TI  - Mint virus X: a novel potexvirus associated with symptoms in 'Variegata' mint.
AB  - Mentha x gracilis 'Variegata', an ornamental mint clone first described about 200
      years ago, exhibits virus-like vein banding symptoms. Double-stranded RNA and
      virion isolations revealed the presence of three viruses in a 'Variegata' plant.
      Cloning and sequencing disclosed that one of the viruses was a previously
      unidentified species with similarities to members of the Flexiviridae family,
      designated as Mint virus X (MVX). The complete nucleotide sequence of the virus
      was determined. Phylogenetic analysis divulged the close relationship of the
      virus with lily virus X and strawberry mild yellow edge virus, members of the
      Potexvirus genus. A reverse transcription-polymerase chain reaction protocol was
      developed and used for detection of MVX in other 'Variegata' plants. All clones
      tested, obtained from nurseries around the United States were infected with MVX,
      making the virus a possible causal agent of the variegated symptoms.

PMID- 16096711
TI  - Genomic and antigenic characterization of viruses from the 1993 Italian foot-and
      mouth disease outbreak.
AB  - The origin and evolution of the type O foot-and-mouth disease viruses (FMDV) that
      caused the outbreak occurrence in Italy in 1993, the first episode of the disease
      in the EU after adoption of a non-vaccination policy in 1991, have been studied
      by the analysis of sequences encoding three main antigenic sites on the viral
      capsid proteins. The phylogenetic tree derived from sequences spanning the
      carboxyterminal end of VP1 showed that these Italian viruses were grouped in the
      ME-SA topotype, closely related to viruses that circulated previously in the
      Middle East. The analysis of the nucleotide sequences in VP1, VP2 and VP3 showed
      a co-circulation during the epizootic of genetic variants, including viruses with
      amino acid replacements in VP3. For some of the isolates analyzed, values of
      fixation of nucleotide substitutions per year were observed in the three regions
      analyzed, ranging from 1.5 to 5.1 x 10(-2). The use of a panel of new monoclonal
      antibodies raised against an isolate from this outbreak, as well as monoclonal
      antibodies to FMDV O1-Switzerland 1965, showed differences in the reactivity
      pattern among some of the Italian isolates analyzed, which were consistent with
      the co-circulation of antigenic variants. These results support the potential for
      FMDV diversification in a limited period of time and under epidemiological
      conditions in which no vaccination campaigns were being implemented.

PMID- 16096712
TI  - Relationship of taurine and other amino acids in plasma and in neutrophils of
      septic trauma patients.
AB  - Recently, an interdependency of plasma taurine and other amino acids as well as
      metabolic and clinical variables implicating therapeutic options was reported.
      This result may be an indication that plasma taurine levels are directly related
      to intracellular levels. Therefore, the aim of this study was to analyse the
      possible relationship between taurine levels in plasma and in neutrophils, the
      relationship to other amino acids, and variables quantifying metabolic impairment
      and severity of sepsis in multiple trauma patients developing sepsis. After
      multiple trauma taurine decreased significantly in plasma in thirty-two patients
      as well as within the neutrophil and does not recover in sepsis. Lower individual
      levels in the neutrophil did not follow lower individual levels in plasma and no
      correlation of taurine in plasma and in the neutrophils could be observed. In
      sepsis, only plasma showed an interdependency of taurine, aspartate, and
      glutamate. No association between taurine plasma or intracellular levels and SOFA
      score as indicator for severity of sepsis or metabolic variables was observed.
      After multiple trauma and in sepsis, taurine uptake in cells (which is regulated
      in different ways), and intracellular taurine (which serves e.g. as an osmolyte)
      can be influenced. Therefore a prediction of the neutrophil taurine pool seems
      not fully possible from taurine plasma levels. Intracellular taurine has some
      unique properties explaining the missing interdependency despite some
      similarities in osmoregulation and metabolic interactions to other amino acids.
      The association of taurine, aspartate, and glutamate in plasma cannot be simply
      transferred to the neutrophils intracellular level. The clinical meaning of the
      plasma correlation remains unclear. A dependency of plasma and neutrophil taurine
      to severity of sepsis and to metabolic variables seems not possible because of
      the multifactorial pathophysiology of sepsis.

PMID- 16096713
TI  - Bone mineral density predicts osteoporotic fractures in elderly men: the MINOS
      study.
AB  - Osteoporosis in men is becoming a public health problem in developed countries.
      Fracture incidence increases with age, and the number of fractures increases
      because of the ageing of the population. We assessed the predictive value of bone
      mineral density (BMD) for osteoporotic fractures evaluated prospectively in a
      large cohort of elderly men and assessed the sensitivity of the T-score =-2 to
      detect men who will sustain a fracture. Fracture incidence was evaluated for 90
      months in 759 men from the MINOS cohort aged 50 and over at baseline. In 74 men,
      77 incident vertebral and peripheral fractures occurred. BMD was measured at
      baseline at the lumbar spine, hip, whole body and distal forearm. The incidence
      of osteoporotic fractures increased with age and with decreasing body weight. In
      men with low BMD (T-score <-2), fracture incidence varied from 2.26 to 3.07
      fractures per 100 person-years and was 2.1 to 3.6 times higher than in men with
      normal BMD. After adjustment for age, body weight and height, baseline BMD was
      3.7 to 7.9% ( P <0.05-0.0001) lower at all the sites of measurement in men who
      sustained a fracture. After adjustment for age, weight and prevalent fractures,
      BMD was predictive of osteoporotic fractures at all the sites. Odds ratios varied
      from 1.28 to 1.89 per 1 SD decrease in BMD ( P <0.05-0.0001). The predictive
      accuracy of BMD for fractures (area under the curve of the receiving operator
      characteristics adjusted for age, weight and prevalent fractures) varied from
      0.643 to 0.712 according to the skeletal site and was higher for the whole body
      than for other sites. Thus, BMD itself has a limited value for determining men at
      an increased risk for fracture. The percentage of incident fractures occurring in
      men with low BMD (T-score <-2) ranged from 13.7% at the trochanter to 44.6% at
      the ultradistal radius. Conversely, 27 to 45% of incident fractures occurred in
      men with mildly decreased BMD (T-score between -1 and -2). In conclusion, BMD
      predicts osteoporotic fractures in men independently of age, body weight and
      prevalent fractures. However, the sensitivity of BMD to detect men at high risk
      of fracture is low. More studies on the predictors of fractures in men, such as
      bone architecture, morphology, biochemical markers of bone turnover and hormonal
      levels, are necessary.

PMID- 16096714
TI  - Osteoporotic pelvic fractures in elderly women.

PMID- 16096715
TI  - Exercise maintains bone density at spine and hip EFOPS: a 3-year longitudinal
      study in early postmenopausal women.
AB  - It is an important aim in the prevention of osteoporosis to stop or decelerate
      bone loss during the early postmenopausal years. Here we report on results of the
      3-year EFOPS exercise trial in osteopenic women. The exercise strategy emphasized
      low-volume high-resistance strength training and high-impact aerobics. Forty
      eight fully compliant women (55.1+/-3.3 years) with no medication or illness
      affecting bone metabolism participated in the exercise group (EG); 30 women
      (55.5+/-3.0 years) served as non-training controls (CG). At baseline there were
      no significant between-group differences with respect to physical fitness, bone
      mineral density, pain and nutritional status. The training consisted of two group
      training and two home training sessions per week. The study participants of both
      groups were individually supplemented with calcium and vitamin D
      (cholecalciferol). Bone mineral density (BMD) was measured by DXA at the lumbar
      spine, proximal femur and distal forearm and by QCT at the lumbar spine. Speed of
      sound and broadband ultrasound attenuation were determined at the calcaneus by
      quantitative ultrasound (QUS). Pain frequency and intensity at different skeletal
      sites were assessed via questionnaire. After 38 months, the following within
      group changes were measured: DXA lumbar spine, EG: 0.8% n.s.; CG: -3.3% P<0.001;
      QCT trabecular ROI, EG: 1.1% n.s; CG: -7.7% P<0.001; QCT cortical ROI, EG: 5.3%
      P<0.001; CG: -2.6% P<0.001; DXA total hip: EG: -0.2% n.s; CG -1.9%, P<0.001; DXA
      distal forearm, EG: -2.8% P<0.001; CG: -3.8% P<0.001; BUA, EG: -0.3% n.s; CG 
      5.4% P<0.001; SOS, EG: 0.3% n.s; CG -1.0% P<0.001. At year 3 between-group
      differences relative to the exercise group were: DXA lumbar spine: 4.1% P<0.001;
      QCT trabecular ROI: 8.8% P<0.001; QCT cortical ROI: 7.9% P<0.001; DXA total hip:
      2.1%, P<0.001; DXA distal forearm: 1.0% n.s.; BUA: 5.8% P<0.05; SOS: 1.3%
      P<0.001. Pain frequency and intensity in the spine significantly decreased in the
      exercise group and increased in the control group, while no between-group
      differences were detected in the main joints. In summary, over a period of 3
      years our low-volume/high-intensity exercise program was successful to maintain
      bone mineral density at the spine, hip and calcaneus, but not at the forearm.

PMID- 16096716
TI  - Low-dose photodynamic therapy increases endothelial cell proliferation and VEGF
      expression in nude mice brain.
AB  - We tested whether low-dose photodynamic therapy (PDT) induces an angiogenic
      response in the normal brain of nude mice (n=20). Normal brains of nude mice were
      subjected to PDT at low doses (Photofrin: 2 mg/kg; optical: 2 J/cm(2) and 4
      J/cm(2)). BrdU (50 mg/kg) was injected (intraperitoneally, i.p.) daily from PDT
      treatment to sacrifice (1 and 2 weeks after PDT). Laser scanning confocal
      microscopy, immunohistochemistry, and immunofluorescence staining were performed
      to assay angiogenic response. Morphological results show no significant tissue
      damage induced by PDT and two- and three-dimensional image analyses revealed no
      significant difference in vascular structure between the areas of exposure to PDT
      and contralateral areas in all mice. However, the number of BrdU immunoreactive
      cells were significantly increased in the areas of PDT treatment compared with
      contralateral hemisphere in both groups, and the number of BrdU-positive cells
      increased in a PDT-dose-dependent manner. Furthermore, immunohistochemical data
      indicate that PDT at these low doses significantly induces the expression of the
      vascular endothelial growth factor (VEGF) in PDT-treated regions in the 1-week
      group, but not in the 2-week group. These data indicate that low-dose PDT results
      in increased VEGF expression and endothelial cell proliferation in normal brains.

PMID- 16096717
TI  - Etiopathogenesis of arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterised by
      progressive fibro-fatty replacement of right ventricular myocardium. Earlier
      studies described ARVC as non-inflammatory, non-coronary disorder associated with
      arrhythmias, heart failure and sudden death due to functional exclusion of the
      right ventricle. Molecular genetic studies have identified nine different loci
      associated with ARVC; accordingly each locus is implicated for each type of ARVC
      (ARVC1-ARVC9). So far five genes have been identified as containing pathogenic
      mutations for ARVC. Though mutations in each of the gene/s indicate disruption of
      different pathways leading to the condition, the exact pathogenesis of the
      condition is still obscure. This review tries to understand the pathogenesis of
      the condition by examining the individual proteins implicated and relate them to
      the pathways that could play a role in the aetiology of the condition. Cardiac
      ryanodine receptor (RYR-2), which regulates intra-cellular Ca(2+) concentration
      by releasing Ca(2+) reserves from the sarcoplasmic reticulum (SR), was the first
      gene for ARVC. The mutation in this gene is believed to disrupt coupled gating of
      RYR-2, causing after-depolarisation, leading to arrhythmias followed by
      structural changes due to altered intra-cellular Ca(2+) levels. Three other genes
      implicated for ARVC, plakoglobin (Naxos disease), desmoplakin (ARVC8) and
      plakophilin (ARVC9) have prompted the speculation that ARVC is primarily a
      disease of desmosomes. But identification of TGFbeta-3 for ARVC1 and the role of
      all these three genes (plakoglobin, desmoplakin and plakophilin) in cardiac
      morphogenesis indicate some kind of signal-transducing pathway disruption in the
      condition. The finding that ARVC as a milder form of Uhl's anomaly indicates
      similar ontogeny for the condition. Further, discovery of apoptotic cells in the
      autopsy of the right ventricular myocardium of ARVC patients does indicate a
      common pathway for different types of ARVCs, which is more specific for the right
      ventricular myocardium involving desmosomal plaque proteins, growth factors and
      Ca(2+) receptors.

PMID- 16096718
TI  - Intrauterine penetrating direct fetal head trauma following gunshot injury: a
      case report and review of the literature.
AB  - CASE REPORT: An unusual case of an intrauterine penetrating head injury due to a
      pellet from an airgun is described. A 28-year-old pregnant woman, at term, shot
      herself intravaginally with a toy BB gun. Following a spontaneous precipitous
      vaginal delivery, the neonate presented with persistent seizure disorder,
      meningitis, cerebritis, and a right parietal region scalp swelling. Imaging
      studies revealed intracranial hemorrhage, and the metallic pellet was adjacent to
      the right lateral ventricle, which was removed through a parietal craniotomy.
      Computed tomography of the brain after 1 week demonstrated early abscess
      formation in the left frontal operculum and a subdural empyema in the posterior
      fossa. The abscesses were evacuated, and the meningitis was treated vigorously
      with broad-spectrum antibiotics. Although well for the past 6 years, the child
      demonstrates significant mental handicap and developmental delay. DISCUSSION: The
      pathogenesis, management, and medicolegal issues pertaining to the above case are
      discussed, and the relevant literature is briefly reviewed.

PMID- 16096719
TI  - Conjugation of multiple copies of polyethylene glycol to hemoglobin facilitated
      through thiolation: influence on hemoglobin structure and function.
AB  - PEGylation induced changes in molecular volume and solution properties of HbA
      have been implicated as potential modulators of its vasoconstrictive activity.
      However, our recent studies with PEGylated Hbs carrying two PEG chains/Hb, have
      demonstrated that the modulation of the vasoconstrictive activity of Hb is not a
      direct correlate of the molecular volume and solution properties of the PEGylated
      Hb and implicated a role for the surface charge and/or the pattern of surface
      decoration of Hb with PEG. HbA has now been modified by thiolation mediated
      maleimide chemistry based PEGylation that does not alter its surface charge and
      conjugates multiple copies of PEG5K chains. This protocol has been optimized to
      generate a PEGylated Hb, (SP-PEG5K)(6)-Hb, that carries approximately six PEG5K
      chains/Hb - HexaPEGylated Hb. PEGylation increased the O(2) affinity of Hb and
      desensitized the molecule for the influence of ionic strength, pH, and allosteric
      effectors, presumably a consequence of the hydrated PEG-shell generated around
      the protein. The total PEG mass in (SP-PEG5K)(6)-Hb, its molecular volume, O(2)
      affinity and solution properties are similar to that of another PEGylated Hb, (SP
      PEG20K)(2)-Hb, that carries two PEG20K chains/Hb. However, (SP-PEG5K)(6)-Hb
      exhibited significantly reduced vasoconstriction mediated response than (SP
      PEG20K)(2)-Hb. These results demonstrate that the enhanced molecular size and
      solution properties achieved through the conjugation of multiple copies of small
      PEG chains to Hb is more effective in decreasing its vasoconstrictive activity
      than that achieved through the conjugation of a comparable PEG mass using a small
      number of large PEG chains.

PMID- 16096720
TI  - Determination of the amino acid sequence of a new phospholipase A(2) (MIDCA1)
      isolated from Micrurus dumerilii carinicauda venom.
AB  - A new Phospholipase A(2) (PLA(2)) from Micrurus dumerilii carinicauda venom was
      isolated and its primary structure determined. This new PLA(2) showed a low
      enzymatic activity when compared with other PLA(2)s and it is moderately basic
      with an isoelectric point of 8.0. Its amino acid sequence showed the presence of
      120 amino acid residues and its sequence was:
      NLIQFLNMIQCTTPGREPLVAFANYGCYCGRGGSGTPVDELDRCCQVHDNCYDTAKKVFGCSPYFTMYSYDCSEGKLTCKD
      NTKCKAAVCNCDRTAALCFAKAPYNDKNYKIDLTKRCQ. The structural model of MIDCA1, when
      compared with other strong neurotoxic PLA(2)s, such as Naja naja, showed
      significant differences in the beta-wing and neurotoxic sites, despite the high
      level of amino acid sequence similarity. These observations indicate a
      dissociation between the biological and catalytic activity of this new PLA(2),
      supporting the view that other regions of the protein are involved in the
      biological effects.

PMID- 16096721
TI  - The role of exoproteases in governing intraneuronal metabolism of botulinum
      toxin.
AB  - Botulinum toxin type A has a long duration of action, and thus it can block
      transmitter release for several weeks to several months. However, little is known
      about the precise mechanism that accounts for termination of toxin action.
      Therefore, experiments were done to gauge the effects of aminopeptidases and
      carboxypeptidases on the structure and function of the toxin. Exoproteases were
      added to the holotoxin, the native light chain, and a recombinant light chain.
      Treated toxin and light chain were examined for their effects on neuromuscular
      transmission and on isolated substrate. The data showed that aminopeptidase
      attack did not alter the N-terminus of the toxin/light chain, nor did it produce
      losses in biological activity. Carboxypeptidase attack did alter the C-terminus
      of the light chain, but not sufficiently to alter biological activity. The data
      suggest that the tertiary structure of the light chain confers upon the molecule
      substantial resistance to exoproteases.

PMID- 16096722
TI  - Physicochemical characterization of the reassembled dimer of an integral membrane
      protein OmpF porin.
AB  - The in vitro reassembled species of OmpF porin, which was renatured from its
      denatured monomer using n-octyl-beta-D-glucopyranoside, was characterized by low
      angle laser light scattering photometry, circular dichroism spectroscopy and
      synchrotron radiation small-angle X-ray scattering measurements. The light
      scattering measurement reconfirmed that the reassembled species was the dimer of
      the protein. Circular dichroism spectra of the reassembled dimer showed a native
      like beta-structure. A small-angle X-ray scattering measurement indicated that
      the size of the reassembled dimer was nearly equal to that of the native trimer
      under the present experimental conditions. In a thermal denaturation experiment
      followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the
      reassembled dimer was less stable than the native trimer.

PMID- 16096723
TI  - A statistical mechanical deconvolution of the differential scanning calorimetric
      profiles of the thermal denaturation of cyanomethemoglobin.
AB  - A differential scanning calorimetric study of the thermal unfolding of horse
      cyanomethemoglobin (as an irreversible protein system) was carried out in
      phosphate-EDTA buffer (20 mM phosphate, 1 mM EDTA) pH 7.2. The calorimetric
      rescanning of the protein solution was found to be irreversible and the process
      unfolded state --> final state appears to follow first order kinetic. Assuming
      the system to be comprised of n reversible states and one irreversible final
      state, the number of particles participating in the reversible states changes
      with time because they ultimately transit to the final irreversible denatured
      state. Hence, we carried out the deconvolution analysis using the grand canonical
      ensembles instead of just the canonical ensembles. This change was effected by
      introducing a correction term into the related equations which determines the
      outlet share of those particles exiting from the reversible states and converting
      into the final irreversible state. This approach provided an improved
      interpretation of the experimental data, which supports the following two-step
      process for the thermal denaturation of cyanomethemoglobin: alpha(2)beta(2) -->
      (alpha + alphabeta + beta)(excited) --> alpha(melt) + (alphabeta)(melt) +
      (beta(melt).

PMID- 16096724
TI  - Comparative study of the conformational lock, dissociative thermal inactivation
      and stability of euphorbia latex and lentil seedling amine oxidases.
AB  - The thermal stability of copper/quinone containing amine oxidases from Euphorbia
      characias latex (ELAO) and lentil seedlings (LSAO) was measured in 100 mM
      potassium phosphate buffer (pH 7.0) following changes in absorbance at 292 nm.
      ELAO was shown to be about 10 degrees C more stable than LSAO. The dissociative
      thermal inactivation of ELAO was studied using putrescine as substrate at
      different temperatures in the range 47-70 degrees C, and a "conformational lock"
      was developed using the theory pertaining to oligomeric enzyme. Moreover ELAO was
      shown to be more stable towards denaturants than LSAO, as confirmed by dodecyl
      trimethylammonium bromide denaturation curves. A comparison of the numbers of
      contact sites in inter-subunits of ELAO relative to LSAO led us to conclude that
      the higher stability of ELAO to temperature and towards denaturants was due to
      the presence of larger number of contact sites in the conformational lock of the
      enzyme. This study also gives a putative common mechanism for thermal
      inactivation of amine oxidases and explains the importance of C-terminal
      conserved amino acids residues in this class of enzymes.

PMID- 16096725
TI  - Stretched-exponential analysis of heat-induced aggregation of apo-concanavalin A.
AB  - The kinetics of heat-induced aggregation of apo-concanavalin A (aConA) was
      investigated as a function of temperature and protein concentration by circular
      dichroism and turbidity. Heat-induced aggregation, as well as conformational
      change, of aConA was fitted to stretched-exponential equations. The exponent of
      the conformational change maintained 0.5 despite the protein concentration and
      temperature, indicating the presence of a common intermediate during the
      conformational change. After the process, aggregates grew with increasing
      temperature and initial protein concentration. The reaction order of aggregation
      was 1.5, indicating that the rate-limiting steps of aConA aggregation involve
      both conformational change and aggregation.

PMID- 16096726
TI  - [Costs of therapy of insulin-treated patients with Diabetes mellitus in Germany.
      Results of the JEVIN trial].
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus, its treatment with oral antidiabetic
      drugs and insulin, self-monitoring and the development of diabetesrelated long
      term complications raise multiple socioeconomic problems. Hence, diabetes is one
      of the major challenges to modern health care systems. To date, there are only
      few data analyzing diabetes-related costs. Therefore, it was the aim of this
      trial to assess the costs of therapy of insulin-treated patients with diabetes
      mellitus out of a selection-free population over a period of 5 years. PATIENTS
      AND METHODS: JEVIN (Jena's St. Vincent trial) is a prospective population-based
      trial of all patients with type 1 and insulin-treated type 2 diabetes mellitus
      aged 16-60 years and living in the city of Jena, Thuringia, Germany. In addition
      to parameters of diabetes control (relative hemoglobin A(1c) [= HbA(1c)/mean
      normal], long-term complications, blood pressure), the costs of therapy in
      respect of insulin and oral antidiabetic drugs and materials to perform self
      monitoring were analyzed in 1999/2000 compared to 1994/95. In 1994/95, 244
      patients, in 1999/2000, 291 patients were examined. RESULTS: During the period
      from 1994/95 to 1999/2000, relative HbA(1c) improved in both patients with type 1
      (1.65 +/- 0.35 [n = 127] vs 1.48 +/- 0.30 [n = 114]; p < 0.0001) and insulin
      treated type 2 diabetes (1.75 +/- 0.40 [n = 117] vs. 1.47 +/- 0.25 [n = 147]; p <
      0.0001). The quality of blood pressure control remained constant. In 1999/2000
      the costs per unit insulin for patients with type 1 diabetes were calculated at
      about 0.078 +/- 0.035 DM, in 1994/95 at 0.075 +/- 0.032 DM (p = 0.873). For
      patients with type 2 diabetes the costs were calculated at 0.070 +/- 0.032 DM in
      1999/2000 and at 0.070 +/- 0.028 DM (p = 0.954) in 1994/95. In 1999/2000, to
      perform blood glucose self-monitoring the costs were 4.08 +/- 1.39 DM/d for
      patients with type 1 diabetes and 3.07 +/- 1.36 DM/d for patients with type 2
      diabetes. In 1994/95 the costs for patients with type 1 diabetes amounted to 3.56
      +/- 1.69 DM/d (p = 0.012), and for patients with insulin-treated type 2 diabetes
      mellitus to 2.77 +/- 1.66 DM/d (p = 0.138). In 1999/2000 the costs for
      antihypertensive drugs in 46/114 patients with type 1 diabetes were calculated at
      about 1.43 +/- 1.10 DM/d. In 1994/95 the costs for 32/127 patients amounted to
      1.76 +/- 1.00 DM/d (p = 0.501). For 104/147 patients with insulin-treated type 2
      diabetes, the costs of antihypertensive drugs were 2.02 +/- 1.48 DM/d in
      1999/2000. In 1994/95 the costs amounted to 1.77 +/- 1.11 DM/d (p = 0.141) for
      54/117 patients. In 1994/95 the total costs for patients with type 1 diabetes
      mellitus were calculated at about 7.10 +/- 2.69 DM/d. In 1999/2000 the costs
      amounted to 7.70 +/- 2.75 DM/d (p = 0.085). In patients with insulin-treated type
      2 diabetes mellitus there was a significant increase in 1999/2000 versus 1994/95
      (1994/95: 6.43 +/- 3.16, 1999/2000: 7.57 +/- 3.56 DM/d; p = 0.007). CONCLUSION:
      Despite a tendency toward an increase in the costs for daily life, the therapy
      related costs for patients with type 1 diabetes mellitus were constant in
      1999/2000 versus 1994/95. In patients with type 2 diabetes, there was an increase
      of about 18%. For both patients with type 1 and type 2 diabetes, the costs were
      substantially higher than calculated in theoretical models.

PMID- 16096727
TI  - [Acute chest pain].
AB  - BACKGROUND: Acute chest pain is very frequent in medicine and caused by several
      cardiac disorders or disorders of the great vessels. In addition, chest pain is
      well known as "noncardiac chest pain" or due to functional abnormalities. For
      prognosis and long-term follow-up, acute coronary syndromes (ACS) and ascending
      aortic dissections are important disorders. RESULTS: The ACS represents a
      heterogeneous group of patients along a continuum of risk from unstable angina
      (UA) to non-ST segment elevation (NSTEMI) to ST segment elevation myocardial
      infarction (STEMI). In patients with NSTEMI/UA, beta-blockers, nitrates and
      calcium antagonists will improve chest pain, and invasive management of ACS is
      indicated in < 48 h, if risk factors are present. In patients without risk
      factors, stress studies and conservative treatment are mandatory. In patients
      with STEMI, nitrates, aspirin, heparin, and beta-blockers are required, and
      therapy of first choice is reperfusion with percutaneous coronary intervention
      (PCI). Acute ascending aortic dissection has a poor prognosis with mortality
      rates of 60% within 24 h, 75% within 1 week, and 90% within 3 months. Immediate
      surgical management of acute type A aortic dissection is necessary, whereas
      conservative treatment is preferred in acute type B aortic dissection. Both types
      require adequate therapy of hypertension. Acute pericarditis is caused by several
      factors; cardiac tamponade with pericarditis or pericardial effusion is
      associated with circulatory compromise and may be life-threatening. Acute
      pericarditis generally takes a benign course after empirical treatment with
      nonsteroidal or steroidal anti-inflammatory drugs. Immediate percutaneous
      pericardiocentesis is required, if cardiac tamponade is present. CONCLUSION: In
      many patients, chest pain is caused by functional abnormalities with impaired
      quality of life. In these, exclusion of an underlying organic heart disease and
      patient information on it are essential.

PMID- 16096728
TI  - [The renin-angiotensin-aldosterone system -- more complex as previously thought].
AB  - BACKGROUND: Angiotensin II (ANG II) is an important factor for the progression of
      renal diseases. ANG II has many pleiotropic effects on the kidney such as pro
      inflammatory and profibrotic actions besides the well-known blood pressure
      increasing effect. NOVEL KNOWLEDGE: Organs have local ANG II-generating systems
      that work independently from their classic systemic counterpart. Renal proximal
      tubular cells could generate and secrete ANG II into the urine in concentrations
      that are 10,000 times higher than those found in serum. These local systems are
      only incompletely blocked by currently used doses of ACE inhibitors or AT(1)
      antagonists. There are other enzyme systems besides ACE that contribute to the
      formation of ANG II. Alternative pathways generate peptides such as angiotensin 1
      7 that have antagonistic effect compared with ANG II. Degradation products of ANG
      II such as angiotensin IV bind at separate receptors and could mediate fibrosis.
      The discovery of AT(1) receptor dimers and agonistic antibodies against AT(1)
      receptors contributes to the complexity of the system. CLINICAL RELEVANCE: The
      complexity of the renin-angiotensin-aldosterone system (RAAS) implies that dual
      blockade with ACE inhibitors and AT(1) receptor antagonists makes sense for
      pathophysiological reasons. First clinical studies have shown that such as dual
      therapy reduces progression of chronic renal disease more efficiently that the
      respective monotherapies in certain risk populations. This shows that novel
      pathophysiological data could lead to innovative clinical treatment strategies.

PMID- 16096729
TI  - [Patient safety and risk management].
AB  - Patient safety is the latest issue in the present stage of the German health care
      system, characterized by costs and quality both resulting in value of care.
      Patient safety defined as "absence of adverse events" represents an important
      problem, because 10% of in-house patients experience an adverse event, which in
      nearly 50% of the cases is due to an error (preventable adverse event). Threats
      and near misses are errors without a consecutive adverse event, much more common
      and better to integrate in the concept of risk management, which is based on
      thorough analysis and prevention of errors in medicine. Chart reviews show
      adverse events in between 3% and 11% of hospital patients, studies with direct
      observation result in higher estimates (17.7%). Nosocomial infections occur in 3
      5%, adverse drug events in 0.17-6.5%, and adverse medical device events in up to
      8% of patients. Medication errors (ordering, dosing, distribution) are present in
      up to 50% of all drug applications. Adverse drug events are important reasons for
      hospital admissions (3.2-10.8% of all admitted patients), other consequences of
      adverse drug events are severe disability and death. Mortality of adverse drug
      events is estimated between 0.04% and 0.95% of all patients. The introduction of
      risk management in the German health care system is one option to prevent a
      malpractice crisis similar to the situation in the US health care system in the
      1990s. Errors are not to be considered only individual but also organizational
      failures. Critical incident report systems (CIRS) can help to increase the
      knowledge about errors, near misses and adverse events, so that prevention of
      errors can take place. On the organizational level, it is an issue of leaderchip
      to convince the members of the organization that prevention of errors has a
      higher priority than punishing and blaming. The medical and other professions, on
      the other side, have to change their self-understanding from the zero mistake
      philosophy to accepting errors as common events. This understanding is a
      prerequisite that analysis can be performed. The participation of patients should
      be strengthened, because public disclosure is an important issue, although the
      scientific evidence for real improvement in health care resulting from public
      disclosure is still inconclusive.

PMID- 16096730
TI  - [Increased calcium as accidental finding].

PMID- 16096731
TI  - [Pancytopenia, arthralgia and myeloneuropathy due to copper deficiency].
AB  - BACKGROUND: Copper deficiency leads to hematologic disorders like pancytopenia.
      In addition, myeloneuropathy was described in a few cases reports. CASE REPORT: A
      71-year-old woman was hospitalized because of increasing pancytopenia and ataxic
      gait, that resulted in a near-complete inability to walk without assistance.
      Additional symptoms included arthralgia, reduced appetite and weight loss.
      Laboratory studies revealed a proteinuria of 3,700 mg/day. Magnetic resonance
      imaging of the cervical and thoracic spine revealed a wedge-shaped signal
      intensity in the dorsal part as a sign of damage in this area. A copper
      deficiency was then identified as the likely underlying cause for the low blood
      cell counts and neurologic deficits. In this patient, the copper deficiency may
      have resulted from a disturbance in absorption due to a partial gastrectomy
      (modified Billroth I) 10 years ago and due to urinary copper loss in view of
      mesangioproliferative glomerulonephritis. A therapy with copper gluconate 3 x 3
      mg/day was initiated. Within 2 weeks, blood cell counts normalized and appetite
      became normal again; just so, arthralgia disappeared. The neurologic symptoms
      persisted, even though the copper substitution continued for 6 months.
      CONCLUSION: Copper deficiency may be a differential diagnosis for hematologic
      abnormalities like pancytopenia, even if a disorder of intestinal resorption or a
      proteinuria occurs. Myeloneuropathy is a rare complication of this deficiency.
      Hemograms may become normal after treatment with oral copper gluconate, but at
      least in the case presented here, neurologic symptomes did not show any
      improvement.

PMID- 16096732
TI  - [Pro and contra: coding of bacteria].

PMID- 16096733
TI  - [Coronary stents. From a simple idea to a medical high-tech device].
AB  - BACKGROUND: Coronary stents were introduced in clinical cardiology in the middle
      of the 1980s, as balloon angioplasty was associated with a high incidence of
      acute vessel closure and restenosis. EVOLUTION OF CORONARY STENTS: However,
      primarily designed to counteract elastic recoil after angioplasty, initial
      results were complicated by acute and subacute stent thrombosis. With the
      introduction of drugs effectively inhibiting platelet aggregation like
      ticlopidine and clopidogrel, stent could exhibit its superiority in comparison to
      angioplasty. Although the incidence of restenosis could be decreased
      significantly by coronary stents, restenosis remained a major drawback of this
      interventional technique. Several modifications of stent design and stent
      material had been tested, but without a real breakthrough. The introduction of
      active stent coating with anti-inflammatory and antiproliferative drugs marks a
      milestone in the development of this technology. With this approach the
      restenosis problem could be, even though not solved, but essentially mitigated.
      Current developments address bioabsorbable materials to make stents compatible
      with new upcoming noninvasive imaging techniques. CONCLUSION: Introduced 20 years
      ago as a simple wire mesh, modified by new designs and materials, and coated by
      highly effective drugs, coronary stents have advanced to medical high-tech
      devices in interventional cardiology.

PMID- 16096734
TI  - [Problems of the internal medicine -- a European perspective].

PMID- 16096735
TI  - [Political issues in internal medicine in Europe].
AB  - What will be the future of Internal Medicine in Europe? Because of rapidly
      growing concerns regarding the position of Internal Medicine in many European
      countries, the European Federation of Internal Medicine (EFIM) has established a
      working group to analyze the situation. Being well aware of the variation of
      working practices in the different countries, the members of the group used an
      "all-European" approach to answer the following questions: -- Are there problems
      for Internal Medicine, what problems and why? -- Why do health care systems of
      the European countries need Internal Medicine? -- Why do the patients need
      Internal Medicine? -- What needs to be done? Internal Medicine is the modern,
      clinical and scientific medical discipline taking care of adult patients with one
      or more complex, acute or chronic illnesses. Internal Medicine is the cornerstone
      of integrated health care delivery service that is needed today. Decision-makers
      in politics and hospitals, insurers, journalists and the general public need a
      better understanding of what Internal Medicine can offer to the health care
      systems and to the individual patient.

PMID- 16096736
TI  - [Malignant epithelioid hemangioendothelioma of the liver. Results of surgical
      treatment strategies].
AB  - BACKGROUND: Malignant epithelioid hemangioendothelioma is a rare vascular tumor
      described mostly in soft tissue, lungs, or liver. The outcome after a wide
      variety of therapeutic measures, ranging from extended surgical therapy to no
      therapy, is reported to be variable. Therefore, we reviewed our experience with
      resective therapy for this rare liver tumor, including orthotopic liver
      transplantation. MATERIAL AND METHODS: During a period of 5 years, seven patients
      with the histological diagnosis of hepatic epithelia hemangioendothelioma were
      seen. In five of them, the liver pathology was detected at random, and all
      patients were prospectively followed. The therapeutic measures and course of
      disease are given as case reports. RESULTS: Three patients received formal liver
      resection and two received liver grafts, one partial and one whole. One further
      patient is scheduled for transplantation and one is undergoing alternative
      therapy, with the tumor remaining stable. All resected patients recovered quickly
      and are alive and well 2 months to 4 years later without signs of tumor
      recidivism. CONCLUSION: Anatomic liver resection, or in the case of diffuse tumor
      spread, orthotopic liver transplantation, show favorable long-term results for
      the treatment of hepatic epithelioid hemangioendothelioma. Therefore, surgical
      therapy is proposed as the treatment of choice for this entity.

PMID- 16096737
TI  - [Efalizumab. Long-term treatment of psoriasis].
AB  - Efalizumab is a humanized monoclonal CD11a-antibody. It inhibits T-cell migration
      and activation which are essential steps in the immunopathogenesis of psoriasis.
      Clinical studies have demonstrated that efalizumab is efficient and safe in the
      treatment of chronic plaque psoriasis. Approximately 30% of patients achieve an
      improvement in PASI of > or =75% within 12 weeks, with further clinical benefit
      noted with continued therapy. Efalizumab thus appears as an important option in
      the long-term management of chronic plaque psoriasis.

PMID- 16096738
TI  - Rocking around the clock, while time is relative.

PMID- 16096739
TI  - Atypical patterns of circadian clock gene expression in human peripheral blood
      mononuclear cells.
AB  - Circadian ( approximately 24 h) rhythms in physiology and behaviour are observed
      in all mammals, including humans. These rhythms are generated by circadian clocks
      located in the hypothalamus and also in most peripheral tissues. Clock genes are
      essential components of circadian clocks, and mutations or polymorphisms within
      several of them have been associated with circadian disorders in humans. However,
      information about human clock gene expression has remained very limited.
      Peripheral blood mononuclear cells (PBMCs) represent an ideal material to
      investigate non-invasively the human clock at the molecular level. In the present
      study, we analysed the expression of three key clock genes, PER2, BMAL1 and REV
      ERBalpha in PBMCs from ten healthy humans over a 24-h cycle. PER2 and BMAL1 were
      found to oscillate throughout the light-dark cycle in all subjects.
      Interestingly, despite normal melatonin and cortisol secretion patterns, two
      groups of subjects could be distinguished with significantly different mean PER2
      and BMAL1 acrophases. BMAL1 oscillated with approximately the same phase as PER2,
      instead of being anti-phasic as anticipated from data previously obtained in
      other peripheral tissues. Furthermore, this unusual phase relationship of PER2
      and BMAL1 in human PBMCs was associated with a constant expression of REV
      ERBalpha, a crucial regulator of BMAL1, which is highly rhythmic in many other
      systems. These results reveal the existence of different chronotypes of clock
      gene expression patterns and suggest specific regulatory mechanisms in human
      PBMCs.

PMID- 16096740
TI  - T-cell-based vaccination for morphological and functional neuroprotection in a
      rat model of chronically elevated intraocular pressure.
AB  - Acute or chronic glaucoma is often associated with an increase in intraocular
      pressure (IOP). In many patients, however, therapeutic pressure reduction does
      not halt disease progression. Neuroprotection has been proposed as a
      complementary therapeutic approach. We previously demonstrated effective T-cell
      based neuroprotection in experimental animals vaccinated with the synthetic
      copolymer glatiramer acetate (copolymer-1, Cop-1), a weak agonist of self
      antigens. This study was undertaken to test different routes and modes of
      vaccination with Cop-1 as treatment modalities for protection against retinal
      ganglion cell (RGC) death caused by chronic elevation of IOP in rats, and to
      determine whether anatomical neuroprotection is accompanied by functional
      neuroprotection. In a chronic model of unilaterally high IOP, Cop-1 vaccination,
      with or without an adjuvant, protected rats against IOP-induced loss of RGCs by
      eliciting a systemic T-cell-mediated response capable of cross-reacting with self
      antigens residing in the eye. In rats deprived of T cells, Cop-1 (unlike
      treatment with alpha2-adrenoreceptor agonists) was not protective of RGCs,
      substantiating the contention that its beneficial effect is not conferred
      directly but is T-cell-mediated. Pattern electroretinography provided evidence of
      functional protection. Thus, vaccination with adjuvant-free Cop-1 can protect
      RGCs from the consequences of elevated IOP in rats. This protection is manifested
      both morphologically and functionally. These findings can be readily implemented
      for the development of a therapeutic vaccination to arrest the progression of
      glaucoma.

PMID- 16096741
TI  - [Skull base tumors].
AB  - Modern imaging techniques have great importance in the diagnosis and therapy of
      skull-base pathologies. Many of these lesions, especially in relation to their
      specific location, can be evaluated using CT and MR imaging. Tumors commonly
      found in the anterior skull base include carcinoma, rhabdomyosarcoma,
      esthesioneuroblastoma and meningioma. In the central cranial fossa,
      nasopharyngeal carcinoma, metastases, meningioma, pituitary adenoma and neurinoma
      have to be considered. The most common neoplasms of the posterior skull base,
      including the CP angle, are neurinoma, meningioma, nasopharyngeal carcinoma,
      chordoma and paraganglioma. One major task of imaging is the evaluation of the
      exact tumor extent as well as its relationship to the neighboring neurovascular
      structures. The purpose of this review is to recapitulate the most important
      anatomical landmarks of the skull base. The typical imaging findings of the most
      common tumors involving the skull base are also presented.

PMID- 16096742
TI  - [New concept minimizes bleeding in radical retropubic prostatectomy].
AB  - BACKGROUND: Radical retropubic prostatectomy is an intervention known to be
      associated with severe bleeding. Even experienced surgeons report a blood
      transfusion rate of up to 20%. The perioperative concept for this intervention
      underwent various modifications in January 2001. This study describes the effect
      of these modifications on the blood loss in a retrospective analysis comparing
      approximately 100 operations by a single experienced surgeon before the change
      (group 1) with 100 operations thereafter (group 2). MATERIALS AND METHODS: The
      new perioperative concept comprised the following points: reducing the
      intravenously applied volume, employing a peridural catheter (PDC), and
      maintaining a 25-30 degrees Trendelenburg's position. The difference in pre- and
      postsurgical hemoglobin (Hb) was analyzed before (group 1) and after the
      intervention (group 2). If transfusions were performed, this value was corrected
      according to the following formula: 1 ml of erythrocyte concentrate increases the
      patient's Hb by 0.003 g/dl. RESULTS: Assessment was possible in 201 of 234 cases,
      110 from the first and 91 from the second group. The mean transfusion-corrected
      Hb difference was 5.3 g/dl in group 1 (20% transfusion rate) and 3.52 g/dl in
      group 2 (1.09% transfusion rate); p>0.0001. The median intravenous volume applied
      was 5.960 ml in group 1 and 3.490 ml in group 2 (p>0.0001). The complication rate
      did not differ between groups. CONCLUSION: The new perioperative concept
      minimizes the intraoperative blood loss during radical open retropubic
      prostatectomy. Transfusions are only necessary in rare cases. The complication
      rate remains unaltered.

PMID- 16096743
TI  - [The aftercare principle for metastasizing prostate cancer. Few diagnostics, much
      support].
AB  - For advanced prostate cancer - not including intermittent strategies - the
      patient is in continual treatment. The effect of the therapy must be controlled
      so that its failure can be determined as soon as possible and a new regimen
      started. As in most cases the progression of the disease can not be stopped, the
      aim of the therapy is to provide the patient with the best possible quality of
      life. In order to carry out therapy, if possible in the patient's usual
      environment, supportive therapies should be used, such as compensation for
      anaemia or pain therapy as required. Skeletal complications can be
      prophylactically treated by the use of biphosphonates.

PMID- 16096744
TI  - [Correlation of degenerative intervertebral disk displacement using MRI with
      discography findings in patients with back pain].
AB  - BACKGROUND: MRI can be too sensitive for detecting degenerative changes and
      commonly displays pathology that is not necessarily responsible for the patient's
      symptoms. METHODS: Retrospectively, we investigated MRI findings and results of
      discography in 23 patients with lower back pain. MRI investigations were
      performed with a 1.0 and 1.5 Tesla device using T1-weighted and T2-weighted
      sagittal plane imaging and T2-weighted transverse plane imaging. RESULTS: Of the
      35 degenerated discs, 16 were detected on MRI as having a high intensity zone
      (HIZ). Eleven of the 35 segments had previous lumbar disc surgery with a HIZ rate
      of 81.8%, whereas the HIZ rate for unoperated segments was only 29.2%.
      CONCLUSIONS: HIZ is known to be a common lesion found using MRI in lower back
      pain patients. In operated segments, we found an incidence of 81.8% and in
      unoperated segments of 28.2%. Discography can discriminate between painful and
      non-painful discs. With the help of additional parameters such as contrast mean
      volume and pain characteristics during puncture, the number of false positive
      discograms can be reduced.

PMID- 16096745
TI  - [Management of spine injuries in polytraumatized patients].
AB  - The management of spine injuries in polytraumatized patients remains a great
      challenge for the diagnostic procedures and institution of appropriate treatment
      by integrating spinal trauma treatment into the whole treatment concept as well
      as following the treatment steps for the injured spine itself. The established
      concept of "damage control" and criteria regarding the optimal time and manner
      for operative treatment of the injured spine in the polytrauma setting is
      presented and discussed.

PMID- 16096746
TI  - Thrombotic microangiopathies and intensive care unit: real advances?

PMID- 16096749
TI  - What is the role of noninvasive ventilation in diastolic heart failure?

PMID- 16096750
TI  - Acute leftward septal shift by lung recruitment maneuver.

PMID- 16096751
TI  - Lung recruitment maneuver depresses central hemodynamics in patients following
      cardiac surgery.
AB  - OBJECTIVE: To assess the impact of the lung recruitment maneuver on circulation
      following cardiac surgery. DESIGN AND SETTING: Prospective randomized cross-over
      study at the Departments of Anesthesia and Thoracic Surgery, Copenhagen
      University Hospital. PATIENTS: Ten adult undergoing coronary artery bypass
      surgery. INTERVENTIONS: Patients were randomized to two durations of lung
      recruitment maneuvers (40 cmH2O airway pressure for 10 s and 20 s or vice versa
      after 5 min) administered immediately after surgery. MEASUREMENTS AND RESULTS:
      Transesophageal echocardiography (left ventricular short axis view), pulse
      contour cardiac output, and arterial blood pressure were monitored continuously.
      Systemic and pulmonary arterial blood gases were sampled before and after each
      lung recruitment maneuver to calculate the intrapulmonary shunt. Left ventricular
      end-diastolic areas decreased significantly during both the 10-s and the 20-s
      lung recruitment maneuvers. Cardiac output was 5.6+/-0.8 l/min at baseline,
      decreasing by 3.0+/-1.1 l/min and 3.6+/-1.2 l/min during lung recruitment
      maneuvers of 10 and 20 s, respectively. Shunt decreased from 20+/-5% to 15+/-6%
      after the first lung recruitment maneuver and from 15+/-6% to 12+/-5% after the
      second. CONCLUSIONS: Lung recruitment maneuvers markedly reduced cardiac output
      and left ventricular end-diastolic areas in hemodynamically stable patients
      following cardiac surgery.

PMID- 16096752
TI  - Microstructured layers of spherical biofunctional core-shell nanoparticles
      provide enlarged reactive surfaces for protein microarrays.
AB  - Nanostructured core-shell particles with tailor-made affinity surfaces were used
      to generate microstructured affinity surfaces by microspotting the particles to
      form densely packed amorphous nanoparticle layers. These layers provided a large
      reactive surface for the specific binding of protein ligands from aqueous
      solution. Biofunctional core-shell particles were synthesized for this purpose
      that consisted of a silica core with a diameter of 100 nm and an organic shell a
      few nm thick. The nanoparticle core was prepared by sol-gel chemistry and the
      shell formed in suspension by organosilane chemistry. The shell provided amino
      groups or carbonyl groups at its outer surface for subsequent covalent
      immobilization of streptavidin, rabbit IgG antibodies or goat IgG antibodies.
      AlexaFluor 647-conjugated and biotinylated cytochrome C and CyDye-labeled anti
      rabbit IgG and anti-goat IgG were probed as model analytes. The core-shell
      nanoparticles were spotted using a pin-ring micro-arrayer onto microscope glass
      slides that were coated with a polycation monolayer by dip-coating prior to
      nanoparticle deposition. Amorphous particle layers of well-defined thicknesses in
      the range of 100 nm to 2 microm were obtained by printing aqueous particle
      suspensions containing 5-500 mg/mL (0.5-50 wt%) of silica particles. The specific
      affinity of the plotted nanoparticulate capture surface was demonstrated by
      binding Cy3-labeled donkey anti-rabbit IgG and Cy5-labeled mouse anti-goat IgG to
      immobilized rabbit IgG and goat IgG particles. The signal intensity per spot
      increased for any given analyte concentration when the amount of particles per
      spot was augmented. This was attributed to the increasing integration of receptor
      molecules per surface footprint, which shifted the binding equilibrium towards
      the formation of the receptor-ligand complex. Additionally, the locally-increased
      supply of receptor molecules at the nanoparticulate microchip surface resulted in
      a wide dynamic range of 4 fM-20 nM (covering six orders of magnitude).

PMID- 16096753
TI  - Extranodal Rosai-Dorfman disease of bone, subcutaneous tissue and paranasal sinus
      mucosa with a review of its pathogenesis.
AB  - We report an unusual case of extranodal Rosai-Dorfman disease presenting in a 36
      year-old man with lesions of bone, subcutaneous tissue of the arm and maxillary
      sinus mucosa unassociated with lymphadenopathy or systemic symptoms. These
      lesions appeared metachronously within a 6-month period. The diagnostic light
      microscopic and immunohistochemical findings and pathogenesis of this interesting
      disease are discussed.

PMID- 16096754
TI  - Sarcoidosis presenting as prepatellar bursitis.
AB  - A 61-year-old woman complained of a subcutaneous mass in her right knee. MR
      images revealed a well-defined subcutaneous mass in the prepatellar region,
      containing some fluid and foci of short T2. The lesion showed some marginal
      contrast uptake after an administration of meglumine gadopentetate (Gd-DTPA),
      consistent with prepatellar bursitis. The pathological specimen, however,
      revealed subcutaneous sarcoidosis involving the bursa.

PMID- 16096755
TI  - Cherubism associated with neurofibromatosis type 1, and multiple osteolytic
      lesions of both femurs: a previously undescribed association of findings.
AB  - We present a patient with neurofibromatosis type 1, with the clinical,
      radiological and histological features of cherubism mandibular lesions, and
      multiple osteolytic, geographic lesions in both femurs, consistent with multiple
      non-ossifying fibromas. We have been unable to find a similar case in the world
      literature. We discuss our findings in relationship with a number of syndromes
      that present clinical, radiological or pathological similarities.

PMID- 16096756
TI  - Infantile lipofibromatosis of the upper limb.
AB  - The imaging features of extensive lipofibromatosis presenting in a 1-day-old
      female infant are reported. This lesion involved her entire right upper limb,
      extending from the axilla to the palm of the hand. Radiographs showed marked
      deformity and thinning of all the right upper-limb bones due to pressure effect
      of soft-tissue enlargement, especially affecting the distal humerus and proximal
      forearm bones. Magnetic resonance imaging showed a huge soft-tissue mass
      infiltrating most of the muscles of the entire upper limb, with bony erosion. The
      mass was largely T1-isointense, moderately T2-hyperintense and showed marked
      enhancement. There were intra-lesional signal changes consistent with fatty
      elements. A lesion debulking procedure was performed and the histology was that
      of lipofibromatosis. The limb was found to be non-viable after the procedure and
      a subsequent above-elbow amputation was performed. Although the resection margins
      were not clear, she had no further recurrence over a subsequent 3-year follow-up
      period.

PMID- 16096757
TI  - [Virtual microscopy: first applications].
AB  - Only recently fast-paced developments in computer technology allowed for the
      digitization of complete histologic slides. The resulting virtual slides may be
      viewed via webbrowser by any number of pathologists or students independent of
      time and location. Usage of a virtual microscope simply requires a computer
      workstation with a fast internet connection, which opens this technology to a
      broad public. A virtual microscopy system consists of three components:
      acquisition, server and client. Such systems are under development by different
      commercial and academic bodies worldwide. We have developed a virtual microscope
      system called vMic (http://www.vmic.unibas.ch) which provides virtual slides of
      very high image quality. Several successfully held online slide seminars and a
      histology course for students in dentistry are freely accessible in the internet.
      With the commercial availability of ultra rapid and easy-to-use slide scanners
      and the fast improvements of technology virtual microscopy will offer many
      applications in teaching, research and diagnostics. Thanks to additional
      functionalities, real microscopes will most likely be replaced by computer
      workstations in a couple of years.

PMID- 16096758
TI  - Redox metals and oxidative abnormalities in human prion diseases.
AB  - Prion diseases are characterized by the accumulation of diffuse and aggregated
      plaques of protease-resistant prion protein (PrP) in the brains of affected
      individuals and animals. Whereas prion diseases in animals appear to be almost
      exclusively transmitted by infection, human prion diseases most often occur
      sporadically and, to a lesser extent, by inheritance or infection. In the
      sporadic cases (sporadic Creutzfeld-Jakob disease, sCJD), PrP-containing plaques
      are infrequent, whereas in transmitted (variant CJD) and inherited (Gerstmann
      Straussler-Scheinker Syndrome) cases, plaques are a usual feature. In the current
      study, representative cases from each of the classes of human prion disease were
      analyzed for the presence of markers of oxidative damage that have been found in
      other neurodegenerative diseases. Interestingly, we found that the pattern of
      deposition of PrP, amyloid-beta, and redox active metals was distinct for the
      various prion diseases. Whereas 8-hydroxyguanosine has been shown to be increased
      in sCJD, and inducible NOS is increased in scrapie-infected mice, well-studied
      markers of oxidative damage that accumulate in the lesions of other
      neurodegenerative diseases (such as Alzheimer's disease, progressive supranuclear
      palsy, and Parkinson's disease), such as heme oxygenase-1 and lipid peroxidation,
      were not found around PrP deposits or in vulnerable neurons. These findings
      suggest an important distinction in prion-related oxidative stress, indicating
      that different neurodegenerative pathways are involved in different prion
      diseases.

PMID- 16096759
TI  - Haplotyping of STR cluster DXS6801-DXS6809-DXS6789 on Xq21 provides a powerful
      tool for kinship testing.
AB  - Short tandem repeat (STR) markers DXS6801 (GATA41B11), DXS6809 (GATA69B129) and
      DXS6789 (GATA31F01) are located in a 3-Mb region on human chromosome Xq21,
      spanning approximately 3-6 cM. Theoretically, this cluster could give rise to
      1,144 different haplotypes in the German population. In fact, genotyping of 806
      males revealed the presence of 207 different haplotypes. Since the three STRs
      have been shown to be in strong linkage disequilibrium (LD), haplotype
      frequencies cannot be computed on the basis of single locus allele frequencies
      alone, but have to be estimated directly instead. In this work, we present data
      on linkage, haplotype frequencies and LD in the German population. To highlight
      the potential of the STR cluster for forensic analysis, we also report two
      examples of its successful application in pedigree-based kinship testing.

PMID- 16096760
TI  - Effect of increasing cardiac preload, sympathetic antagonism, or vasodilation on
      visceral blood flow during pneumoperitoneum.
AB  - BACKGROUND AND AIMS: An impaired visceral perfusion caused by pneumoperitoneum
      may contribute to morbidity after laparoscopic surgery. The following three
      therapeutic concepts: increasing cardiac preload, controlled vasodilation, or
      selective sympathetic antagonism, were evaluated regarding a possible increase of
      visceral blood flow during pneumoperitoneum with carbon dioxide. METHODS: Forty
      three pigs were assigned to treatment with an increase of preload and
      vasodilation (group A) or selective sympathetic antagonism with esmolol (group
      B). In both groups, pigs were assigned to head-up, head-down, or supine position.
      Perfusion of the vena porta and renal artery was measured by transonic volume
      flow meters and documented before capnoperitoneum, after induction of a 14-mmHg
      capnoperitoneum in each body position, after controlled vasodilation with sodium
      nitroprusside, and after controlled increase of intravascular volume by colloidal
      infusion. RESULTS: Increasing intravascular volume improved portal blood flow in
      all body positions (p<0.05), but not renal blood flow. Medication of esmolol did
      not alter the measured parameters in any body position compared to control.
      Vasodilation with sodium nitroprusside reduced renal blood flow in supine and in
      head-up position. CONCLUSION: An optimal intravascular volume was most effective
      in improving portal blood flow during capnoperitoneum in this trial. Esmolol had
      no negative effects on portal and renal blood flow. Patients with renal
      dysfunction might be treated carefully with sodium nitroprusside during
      capnoperitoneum.

PMID- 16096761
TI  - Pylorus-preserving gastrectomy in gastric cancer surgery--open and laparoscopic
      approaches.
AB  - BACKGROUND AND AIMS: Pylorus-preserving gastrectomy (PPG) has been accepted as a
      function-preserving procedure for early gastric cancer for the prevention of
      postgastrectomy syndrome. In general, PPG procedures have not included
      suprapyloric lymph node dissection to preserve the pyloric branch of the vagal
      nerve and the right gastric artery. The aim of this article is to describe
      procedures for PPG. The technique of laparoscopy-assisted pylorus-preserving
      gastrectomy (LAPPG) is also introduced because PPG is an ideal application for
      laparoscopic surgery. PATIENTS/METHODS: Between September 2000 and September
      2004, we performed 37 cases of conventional PPG and further 73 cases of LAPPG. In
      these patients, PPG including complete lymph node dissection around the remnant
      pyloric cuff was performed. For this purpose, it is recommended that the blood
      flow to the pyloric cuff be maintained by preserving the infrapyloric artery.
      RESULTS: All the patients showed good postoperative recovery, and no
      intraoperative or postoperative major complications were observed. No sign of
      recurrence was found in these 110 patients, and none of them demonstrated dumping
      syndrome. CONCLUSION: The procedures of both PPG and LAPPG are technically
      feasible and have an important role in the surgical management of early gastric
      cancer in terms of better quality of postoperative life, even with
      lymphadenectomy including combined suprapyloric lymph node dissection and right
      gastric artery division.

PMID- 16096762
TI  - Fecal incontinence: an up-to-date critical overview of surgical treatment
      options.
AB  - BACKGROUND: Surgery is the last resort for patients suffering from severe fecal
      incontinence. The armamentarium of surgical options for this condition has
      increased impressively during the last decade. Nevertheless, this fact seems to
      make neither patients nor surgeons feel more comfortable. Treatment of fecal
      incontinence still remains a challenge to modern medicine due to many specific
      sides of this problem. AIMS: This article gives an up-to-date overview of
      existing operative treatment options. METHODS: An unbiased review of relevant
      literature was performed to assess the role of all methods of surgical treatment
      for fecal incontinence available nowadays. RESULTS: Recent studies have shown
      poor late results after primary sphincter repair and low predictive value for
      most preoperative diagnostic tests. New surgical options such as artificial
      devices and electrically stimulated muscle transpositions are doomed by low
      success rates and unacceptably frequent complications. That is why current
      attention has focused on non- or minimally invasive therapies such as sacral
      nerve stimulation and temperature-controlled radio-frequency energy delivery to
      the anal canal. However, all these innovative techniques remain experimental till
      enough high-evidence data are gathered for their objective evaluation.
      CONCLUSION: Careful and detailed preoperative assessment to exactly determine the
      etiology of incontinence and individual approach remain the cornerstones of
      surgical treatment of fecal incontinence nowadays.

PMID- 16096763
TI  - Two-stage continuous operation of recombinant Escherichia coli using the
      bacteriophage lambda Q- vector.
AB  - A two-stage continuous culture of Escherichia coli in combination with a
      bacteriophage lambda system was performed in order to overcome the intrinsic
      plasmid instability that is frequently observed in recombinant fermentation. A
      phage lambda vector with a Q(-) mutation was used to enhance the expression of
      the lambda system. The optimal values of the important operational variables such
      as the substrate concentration, the dilution rate, and the mean residence time on
      the expression of the cloned gene were determined in both batch and continuous
      cultures. For all culturing modes, the full induction of the cloned gene was
      observed 4 h after the temperature shift. In the two stage continuous culture,
      the overproduction reached their maxima at D=0.25 h(-1) with 1.5 S(0) of the
      medium supply. The maximum productivity of the total beta-galactosidase was
      16.3x10(6) U l(-1) h(-1), which was approximately seven times higher than that in
      the single-copy lysogenic stage. The recombinant cells were stable in the
      lysogenic state for more than 260 h, while they were stable for 40 h in the lytic
      state. The instability that developed rapidly in the second tank is believed to
      be due to the accumulation of lysis proteins as a result of vector leakage during
      the operation.

PMID- 16096764
TI  - Single-cell-bioreactors as end of miniaturization approaches in biotechnology:
      progresses with characterised bioreactors and a glance into the future.
AB  - Incidents with single cells and their genesis have not been the major focus of
      science up to now. This fact is supported by the difficulties one faces when
      wanting to monitor and cultivate small populations of cells in a defined
      compartment under controlled conditions, in vitro. Several approaches of up- and
      down-scaling have often led to poorly understood results which might be better
      elucidated by understanding the cellular genesis as a function of its
      microenvironment. This review of the approaches of scale-up and scale-down
      processes illustrates technical possibilities and shows up their limitations with
      regard to obtainable data for the characterisation of cellular genesis and impact
      of the cellular microenvironment. For example, stem cell research advances
      underline the lack of information about the impact of the microenvironment on
      cellular development. Finally, a proposal of future research efforts is given on
      how to overcome this lack of data via a novel bioreactor setup.

PMID- 16096765
TI  - Effects of colloidal fouling and gas sparging on microfiltration of yeast
      suspension.
AB  - Cross-flow microfiltration is an important step in separating Baker's yeast
      (Saccharomyces cerevisiae) from aqueous suspension in many processes. However the
      permeate flux often declines rapidly due to colloidal fouling of membranes and
      concentration polarisation. The present work explores the possibility of
      maintaining acceptable permeate flux by co-current sparging of gas along with the
      feed, which would scour away colloidal deposits and reduce concentration
      polarisation of membranes. In this work, both washed and unwashed yeast were used
      to study the effect of washing to reduce protein fouling of membranes. It was
      found that permeate flux increased by 45% for liquid throughput of 75 kg/h for a
      feed concentration of 2.0 kg/m3 of washed yeast as compared with unwashed yeast
      suspension without gas sparging. For washed yeast suspension, the increase in gas
      flow rate from 0.5 lpm to 1.5 lpm (30 l/h to 90 l/h) had beneficial effect on
      permeate flux. It is concluded that in the present case, the gas flow rate should
      be less than or equal to the liquid flow rate for enhancement of permeates flux.

PMID- 16096766
TI  - [Acceptance of recommendations and guidelines for pain therapy with opioids].
AB  - The practical impact of guidelines for long-acting opioids is estimated to be
      low. This is not solely due to their quality or kind of implementation. Their
      core problem is to build a consensus across contradicting facts which resulted
      until recently in somewhat ambiguous recommendations. Coming guidelines on pain
      management with the aid of opioids should better connect controversial positions
      and analyze upcoming paradoxes: while analgesic or adverse long-term effects are
      still unproven for all opioids the consumption is rising, but severe pain remains
      often inadequately managed. The article analyses some of those paradoxes and
      gives propositions for guidelines, which may lead to their better practical
      acceptance.

PMID- 16096767
TI  - [Opioid-induced analgesia and hyperalgesia].
AB  - Opioids are frequently used for the treatment of moderate to severe acute and
      chronic pain. However, clinical evidence suggests that opioids can elicit
      increased sensitivity to noxious stimuli suggesting that administration of
      opioids can activate both, pain inhibitory and pain facilitatory systems. Acute
      receptor desensitization via uncoupling of the receptor from G proteins,
      upregulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA)
      receptor system and descending facilitation have been proposed as potential
      mechanisms underlying opioid-induced hyperalgesia. The tolerance results from a
      pain sensitization process more than from a decrease in the opioid effectiveness.
      Opioid-induced hyperalgesia and tolerance are observed both in animal and human
      experimental models. Brief exposures to mu-receptor agonists induce long-lasting
      hyperalgesic effects for days. Furthermore, the prolonged use of opioids in
      patients often requires increasing doses and may be accompanied by the
      development of abnormal pain. Successful strategies that may decrease or prevent
      opioid-induced hyperalgesia include the concomitant administration of drugs such
      as NMDA antagonists, alpha(2)-agonists, or nonsteroidal anti-inflammatory drugs
      (NSAID), opioid rotation, or combinations of opioids with different receptor
      selectivity.

PMID- 16096768
TI  - [Does genomics determine efficacy of analgesics?].
AB  - Recent advances in knowledge about gene structure derived from the human genome
      project has also revealed data on genomic variation and their possible impact on
      complex and acute diseases as well as pharmacotherapy. The hypothesis of a
      genetic predisposition for complex diseases such as pain syndromes, side effects,
      and adverse outcomes challenging the clinician is ready to be tested by advanced
      genetic-epidemiologic study designs employing the latest genotyping technology.
      In pain therapy, the genetic background of the efficacy of analgesics, especially
      of opioids, is of particular interest. Genetic differences in drug kinetics and
      dynamics, e.g., differences in metabolism or genetic variations of the drug
      target (e.g., receptors) will be of importance in the future. Pharmacogenetics
      can individualize pharmacotherapy and improve care by predicting the optimal dose
      and avoiding side effects and toxicity in individual patients.

PMID- 16096769
TI  - [Recurrent disc herniation during chronic pain therapy].
AB  - Patients receiving ongoing palliative pain therapy, either by intrathecal
      morphine application or a spinal cord stimulation system (SCS), should obtain
      functional tests of the implant and new diagnostic imaging if new symptoms of
      lumbar pain of changed quality appear. Six cases are presented in which a further
      operation of a recurrent disc herniation resulted in a significant reduction of
      preoperative complaints.

PMID- 16096770
TI  - The use of an insuflon device for the administration of G-CSF in pediatric cancer
      patients.
AB  - In pediatric oncology, granulocyte colony-stimulating factor (G-CSF) is applied
      with the aim of shortening neutropenic periods after chemotherapy and for
      mobilization of peripheral blood stem cells for apheresis procedures. G-CSF is
      administered, subcutaneously or intravenously, on a daily basis. An insuflon
      device for the administration of G-CSF was used in 29 patients for 93 G-CSF
      periods. Retrospective evaluation shows that this administration route is
      feasible, safe and preferred by young children rather than by teenagers with
      cancer.

PMID- 16096771
TI  - The effect of a multidimensional exercise intervention on physical capacity, well
      being and quality of life in cancer patients undergoing chemotherapy.
AB  - The aim of the present study was to investigate the impact of a multidimensional
      exercise intervention focusing on physical capacity; one-repetition maximum (1RM)
      and maximum oxygen uptake (VO2Max), activity level, general well-being and
      quality of life in cancer patients undergoing chemotherapy. The intervention
      comprised resistance and fitness training, massage, relaxation and body-awareness
      training. Eighty-two cancer patients, with or without evidence of residual
      disease, were included: 66 patients with 13 different types of solid tumours and
      16 patients with 6 types of haematological malignancies. The patients trained in
      mixed groups for 9 h weekly for 6 weeks. Physical capacity, physical activity
      level and psychosocial well-being as measured by the Medical Outcomes Study 36
      item Short-Form Health Survey and the European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire C30 were assessed pre- and post
      intervention. Highly significant increases were achieved in muscular strength
      (p<0.001), physical fitness (p<0.001) and physical activity levels (p<0.001). The
      patients reported significant reduction in treatment-related symptoms, i.e.,
      fatigue (p=0.006) and pain (p=0.03). Highly significant improvements were
      observed in physical functioning (p<0.001) and role functioning (p<0.001). Even
      patients with advanced disease were able to improve their results after 6 weeks.
      It is concluded that a multidimensional exercise intervention, including
      resistance training, may be beneficial for cancer patients undergoing
      chemotherapy. This study indicates significant clinical meaningful improvements.
      The exact role of the intervention has to be defined in a randomized controlled
      design. A clinically controlled trial including 250 patients is currently being
      carried out.

PMID- 16096772
TI  - A phase II study of methylphenidate for the treatment of fatigue.
AB  - BACKGROUND: Cancer-related fatigue (CRF) is one of the most distressing symptoms
      patients experience and is seen well after the completion of treatment.
      Methylphenidate (Ritalin) use includes the treatment of opiate-induced
      somnolence, depression, and reduced cognition. This phase II study was performed
      to evaluate the effects of methylphenidate on CRF. PATIENTS AND METHODS: The
      criteria for the eligibility of patients included the following: a history of
      breast cancer, absence of disease for greater than 6 months but less than 5
      years, a hemoglobin level of >12 g%, less than moderate depression on the Brief
      Zung Self-administered Depression Scale, and a score of > or =4 on the Brief
      Fatigue Inventory (BFI). Patients received methylphenidate, 5 mg, orally, twice
      daily, for 6 weeks, with a dose escalation on week 2 if the BFI score remained >
      or =4 and no significant toxicities were reported. A response was defined as a
      decrease in the BFI score of at least two points on weeks 4 and 6 as compared to
      baseline. RESULTS: Between May 2001 and May 2003, 37 patients were entered and
      treated. On weeks 4 and 6, 20 of 37 (54%) responded with a decreased BFI score
      greater than two points, averaging a decrease of 3.5. Although six patients (19%)
      withdrew due to adverse events, these were reported as grade 1. CONCLUSION: This
      study suggests that women with breast cancer who are suffering from moderate to
      severe fatigue may benefit from methylphenidate.

PMID- 16096773
TI  - Primary thoracoplasty and pedicle screw instrumentation in thoracic idiopathic
      scoliosis.
AB  - Thoracoplasty in combination with spine fusion is an established method to
      address the rib cage deformity in idiopathic scoliosis. Most reports about
      thoracoplasty and scoliosis correction focused on Harrington or CD
      instrumentation. We report a retrospective analysis of 21 consecutive patients,
      who were treated with pedicle screw instrumentation for idiopathic thoracic
      scoliosis and concomitant thoracoplasty. Minimal follow up was 24 (24-75) months.
      Indication for thoracoplasty was clinical rib prominence of more than 15 degrees
      . In average there was a 44% correction of clinical rib hump, from 18 (15-25
      degrees ) to 10 degrees (0-18 degrees ) (p<0.0001) and a 40% correction of
      radiological rib hump, from 15 (5-20 degrees ) to 9 degrees (2-15 degrees )
      (p<0.0001). The preoperative pulmonary function, accessed by forced vital
      capacity (FVC) and one-second forced expiratory volume (FEV1), remained unchanged
      at the last follow up. The distal end of fusion was the end vertebra of the curve
      in 83.3% and the end vertebra plus one in 16.7% of the patients. There was a 68%
      correction of instrumented primary thoracic curves, from 60 (45-85 degrees ) to
      19 degrees (5-36 degrees ) (p<0.0001), and a 45% correction of non-instrumented
      secondary lumbar curves, from 40 (28-60 degrees ) to 22 degrees (8-38 degrees )
      (p<0.0001). Apical vertebral rotation (AVR) of the thoracic curves improved 54%,
      from 24 (10-35 degrees ) to 11 degrees (5-20 degrees ) (p<0.0001). The tilt of
      lowest instrumented vertebra (LIV) improved 68%, from 28 (20-42 degrees ) to 9
      degrees (3-20 degrees ) (p<0.0001). There was no significant change in sagittal
      profile of the spine. Analysis with SRS-24 questionnaire showed that the majority
      of the patients were very satisfied with the outcome. A matched control group
      (n=21) operated by the same surgeon with the same operation technique but without
      concomitant thoracoplasty was chosen for comparison. The scoliosis correction in
      the two groups was comparable. The patients without thoracoplasty had 37%
      spontaneous improvement of the clinical rib hump.

PMID- 16096774
TI  - [Antiangiogenic and anti-immunosuppressive therapeutic strategies in human head
      and neck squamous cell carcinoma (HNSCC)].
AB  - BACKGROUND: Angiogenesis and tumor-associated immunosuppression are two of the
      hallmarks of carcinogenesis. In previous studies we demonstrated in vitro that
      HNSCC tumor cells attract monocytes via monocyte chemotactic protein-1 (MCP-1)
      and activate them via transforming growth factor-beta 1(TGF-beta1) to secrete
      interleukin (IL)-1alpha, which in turn stimulates tumor cells to secrete
      increased levels of the angiogenic and immunosuppressive vascular endothelial
      growth factor (VEGF). These findings suggest that interaction between the immune
      system and VEGF-mediated angiogenesis is important for progression of HNSCC.
      Recent studies in vitro show that retinoic acid (RA) downregulates the release of
      MCP-1 and TGF-beta1 by tumor cells. Therefore, we investigated the ability of RA
      to modulate the ability of tumor cells to recruit and activate monocytes for
      participation in VEGF-mediated angiogenesis and immunosuppression in vivo.
      MATERIAL AND METHODS: Mice (ten/group) were injected daily with RA (160
      microg/kg) for 3 weeks. After that time mice were sacrificed, and paraffin
      sections of tumors were obtained and stained for VEGF-A, CD68, and PECAM (CD31)
      by immunohistochemistry. The lungs, liver, and myocardium were analyzed for macro
      and micrometastases. The plasma protein levels of VEGF-A and MCP-1 were
      determined by ELISA. RESULTS: In RA-treated mice tumors regressed completely and
      RA prevented metastases (p=0.00) and macrophage infiltration (p=0.007). Treated
      mice downregulated VEGF-A (0 pg/ml) and MCP-1 (12 pg/ml) in peripheral blood
      (p=0.001). CONCLUSION: Our findings suggest a new therapeutic possibility: the
      development of treatment protocols that can block each of the ways in which
      tumors induce new blood vessel growth and immunosuppression of the host.

PMID- 16096775
TI  - Evaluation of non-automated techniques for phenotypic detection of VanA-type
      Staphylococcus aureus.
AB  - The study presented here was performed to evaluate the ability of various
      nonautomated in vitro susceptibility testing methods to detect glycopeptide
      resistance in the three presently identified strains of VanA-type methicillin
      resistant Staphylococcus aureus. To this end, MICs were determined according to
      the guidelines of the National Committee for Clinical Laboratory Standards, the
      Comite de l'Antibiogramme de la Societe Francaise de Microbiologie and the
      British Society for Antimicrobial Chemotherapy and by using the E-test, agar disc
      diffusion, agar screening plates, and ATB galleries. In each of these methods,
      vancomycin was more efficient than teicoplanin for detecting glycopeptide
      resistance.

PMID- 16096776
TI  - Diagnostic value of bacterial stool cultures and viral antigen tests based on
      clinical manifestations of acute gastroenteritis in pediatric patients.
AB  - The study presented here aimed to elucidate the diagnostic value of bacterial
      stool cultures and viral antigen tests when performed based on the clinical
      characteristics of acute gastroenteritis in infants and young children. A total
      of 21 (11.2%) bacterial and 74 (39.6%) viral infections affecting 187 children
      under the age of 3 years was investigated. Blood (p<0.001) and mucus (p=0.014) in
      the stool and a C-reactive protein (CRP) level of >or=50 mg/l (p=0.006) were more
      significantly associated with gastroenteritis of bacterial rather than viral
      origin. Vomiting (p<0.001) was significantly associated with viral
      gastroenteritis. Among children with bloody stool, culture grew a Salmonella spp.
      in 35% and for vomiting children, stool antigen tests detected rotavirus in 60%
      of cases. In conclusion, etiologic tests to determine the cause of childhood
      gastroenteritis according to their characteristic clinical features or laboratory
      test results, or both, are of low diagnostic value.

PMID- 16096777
TI  - Determination of tetanus antibodies by a double-antigen enzyme-linked
      immunosorbent assay in individuals of various age groups.
AB  - In this study, tetanus immunity was determined in 549 randomly chosen individuals
      of various age groups in Ankara, Turkey. Antibody levels in sera of the
      individuals were measured using a double-antigen enzyme-linked immunosorbent
      assay. Overall, 66.5% (95%CI, 62.4-70.4) of the population studied was found to
      have basic protection (>or=0.01 IU/ml) against tetanus. Protective levels of
      tetanus antibodies declined progressively with age. The rate of protection in
      children and adolescents (aged<20 years) exceeded 90%, while only 16.3% (95%CI,
      8.9-26.2) of those over 60 years of age were protected. Females over 60 years of
      age were less immune than males of the same age group (p=0.034). Although the
      rates of protection in children and adolescents are regarded as satisfactory, the
      rates among adults are low. Preventive measures against tetanus should therefore
      focus on scheduled booster immunization for adults as well as children.

PMID- 16096778
TI  - Necrotizing cervical lymphadenitis due to disseminated Histoplasma capsulatum
      infection.

PMID- 16096779
TI  - Can stooped posture explain multidirectional postural instability in patients
      with Parkinson's disease?
AB  - To determine the effects of the stooped posture of patients with Parkinson's
      disease (PD) on postural stability, we compared the kinetic, kinematic, and
      electromyographic responses of seven subjects with PD and 11 control subjects to
      eight directions of surface translations. Control subjects were studied in an
      upright posture and in a stooped posture that mimicked the posture of the PD
      subjects. When control subjects adopted a stooped posture, peak center of
      pressure displacements slowed and decreased, reducing stability margins toward
      values observed in PD subjects. Stooped control subjects, however, responded to
      translations with large joint angle displacements, whereas PD subjects exhibited
      small joint angle displacements. Stooping in control subjects did not lead to
      abnormally directed horizontal forces under each foot or antagonistic muscle co
      activation at the hip and trunk, as seen in PD subjects. Upright and stooped
      control subjects never fell during the trials, whereas PD subjects fell in 16% of
      the trials. We conclude that stooped posture is a destabilizing posture, but it
      does not account for abnormal postural responses in PD.

PMID- 16096780
TI  - Age-related changes in grasping force modulation.
AB  - The aim of this study was to determine the effect of age on the modulation of
      forces produced by the digits and to determine the effects of practice on the
      control of these forces in young and older adults. Young (n = 14, 19-28 years)
      and old (n = 12, 67-75 years) adults used a precision grip to perform a variable
      force-tracking task (sine wave, 5-25% of maximum voluntary force) with their
      dominant hand. Participants performed 100 practice trials over 2 consecutive
      days. Results indicated that both groups improved accuracy of force tracking as a
      result of practice. Younger adults performed the task at a higher level in pre-
      and post-test conditions compared with older adults. Younger adults showed
      improvements in force control in force generation and release phases. Older
      adults reached performance levels comparable with younger adults' pre-test
      performance, but only after extended practice. In contrast to young adults, older
      adults' performance during the force release phases remained quite variable.
      These data suggest that older adults are impaired in the accurate release of grip
      force. Varied force release patterns that disrupt the precision of force
      modulation may contribute to older adults' diminished dexterous abilities.

PMID- 16096781
TI  - Switching, plasticity, and prediction in a saccadic task-switch paradigm.
AB  - Several cognitive processes are involved in task-switching. Using a
      prosaccade/antisaccade paradigm, we manipulated both the interval available for
      preparation between the cue and the target and the predictability of trial
      sequences, to isolate the contributions of foreknowledge, an active switching
      (reconfiguration) process, and passive inhibitory effects persisting from the
      prior trial. We tested 15 subjects with both a random and a regularly alternating
      trial sequence. Half of the trials had a short cue-target interval of 200 ms, and
      half a longer cue-target interval of 2,000 ms. When there was only a short
      preparatory interval, switching increased the latencies for both prosaccades and
      antisaccades. With a long preparatory interval, switching was associated with a
      smaller latency increase for prosaccades and, importantly, a paradoxical
      reduction in latency for antisaccades. Foreknowledge of a predictable sequence
      did not allow subjects to reduce switch costs in the manner that a long
      preparatory cue-target interval did. In the trials with short preparatory
      intervals, the effects on latency attributable to active reconfiguration
      processes were similar for prosaccades and antisaccades. We propose a model in
      which the passive inhibitory effects that persist from the prior saccadic trial
      are due not to task-set inertia, in which one task-set inhibits the opposite task
      set, but to inhibition of the saccadic response-system by the antisaccade task,
      to account for the paradoxical set-switch benefit for antisaccades at long cue
      target intervals. Our findings regarding foreknowledge show that previous studies
      used to support task-set inertia may have conflated the effects of both active
      reconfiguration and passive inhibitory processes on latency. While our model of
      response-system plasticity can explain a number of effects of dominance asymmetry
      in switching, other models fail to account for the paradoxical set-switch benefit
      for antisaccades.

PMID- 16096782
TI  - The disynaptic group I inhibition between wrist flexor and extensor muscles
      revisited in humans.
AB  - The present studies are designed to further characterise the interneuronal
      pathway mediating the disynaptic reciprocal group I inhibition between flexors
      and extensors at the wrist and the elbow levels in humans. In the first series of
      experiments, we compared the electrical threshold of the reciprocal group I
      inhibition at the wrist and the elbow level after a prolonged vibration aimed at
      raising the electrical threshold of the antagonistic activated Ia afferents.
      Prolonged vibration to the 'conditioning' tendon, which raised significantly the
      electrical threshold of the inhibition at the elbow level, did not alter it at
      the wrist level. These results suggest that the dominant input to the relevant
      interneurones is Ia in origin at the elbow level but Ib in origin at the wrist
      level. In the second series of experiments, using the spatial facilitation
      method, we compared the effects on the post-stimulus time histograms of single
      voluntarily activated motor units of two volleys delivered both separately and
      together to group I afferents in the nerves supplying the homonymous and
      antagonistic muscles. At the wrist, but not at the elbow level, the peak of
      homonymous monosynaptic group I excitation was reduced on combined stimulation,
      although the antagonistic IPSP was just at the threshold. Because the suppression
      did not involve the initial bins of the peak, it is argued that the suppression
      is not due to presynaptic inhibition of Ia terminals, but probably reflects
      convergence between the homonymous and antagonistic volleys onto the
      interneurones mediating the disynaptic inhibition. Taken together with the
      previously reported effects of recurrent inhibition on reciprocal inhibition,
      these results suggest that inhibition between flexors and extensors is
      differently organised at the elbow (reciprocal Ia inhibition) and the wrist (non
      reciprocal group I inhibition) levels. It is argued that the particular
      connectivity at the wrist level might correspond to some functional requirements
      at this ball joint.

PMID- 16096783
TI  - Somatotopy and movement representation sites following cortical stroke.
AB  - Stroke has been associated with many changes in motor system function, but there
      has been limited study of changes in somatotopic organization. This was examined
      in a group of patients with cortical stroke affecting primary sensorimotor
      cortex. In 17 patients with good outcome after cortical stroke involving
      precentral and/or postcentral gyri, plus 14 controls, four functional MRI
      evaluations of brain activity were obtained: finger, shoulder, and face motor
      tasks plus a sensory task, passive finger motion. For each, coordinates for
      contralateral primary sensorimotor cortex activation site were determined, as was
      a measure of inter-hemispheric balance. The normal motor somatotopy measured in
      controls was largely preserved after stroke. The main difference found between
      controls and patients was that the face was lateral to finger motor activation in
      all controls, but face was centered medial to finger in 43% of patients. Among
      patients, smaller infarct volume was associated with more ventral, and larger
      infarct with more dorsal, contralateral primary sensorimotor cortex activation.
      On the other hand, better behavioral outcome was associated with a more
      posterior, and poorer outcome with more anterior, activation. Larger infarct and
      poorer behavioral outcome were each associated with a change in inter-hemispheric
      balance towards the non-stroke hemisphere. Shifts in contralateral movement
      representation site did not correlate with changes in inter-hemispheric balance.
      Motor somatotopy is generally preserved after injury to primary sensorimotor
      cortex. Greater injury and larger behavioral deficits are associated with
      distinct effects on movement representation sites. Changes in motor organization
      within and between hemispheres arise independently after stroke.

PMID- 16096784
TI  - Kindling modifies morphine, cocaine and ethanol place preference.
AB  - Brailowsky and Garcia (1999) proposed the existence of a relationship between
      epilepsy and addiction. To prove this hypothesis, pentylenetetrazol kindled rats
      were tested in the conditioned place preference (CPP) paradigm for their reaction
      to various addictive drugs with different modes of action (morphine, cocaine and
      ethanol). In separate experiments, locomotor activity and body temperature after
      application of the same drugs were tested in kindled and non-kindled rats. In the
      CPP experiment there were significant differences between both groups of rats.
      Non-kindled animals showed place preference to morphine (5.0 mg/kg) or cocaine
      (20.0 mg/kg). This reaction was abolished in the kindled rats. Moreover, control
      rats demonstrated aversion to 2.0 g/kg ethanol. However, ethanol aversion was not
      detectable in kindled rats. Moreover, there was no difference between non-kindled
      and kindled rats in locomotor activity and body temperature after morphine (1.0
      and 5.0 mg/kg), cocaine (10.0 and 20.0 mg/kg), or ethanol (0.5 and 2.0 g/kg)
      application. This suggests alterations in reward systems as a consequence of
      kindling. It is hypothesised that GABAergic neurones in the ventral tegmental
      area might play a major role in the alterations found.

PMID- 16096785
TI  - Cognitive dimensions of orthographic stimuli affect occipitotemporal dynamics.
AB  - Previous research documented letter-string specific cortices in the ventral
      visual stream near the left occipitotemporal junction (i.e., anterior fusiform
      gyrus). These neural areas potentially code the perceptual elements comprising
      orthographic stimuli, and thus function as feature detectors in high-level
      vision. While abundant evidence supports this region's role in detecting
      isomorphic perceptual features, any influence cognitive dimensions (e.g., the
      lexicality of letter-strings) may play in modulating this area's processing
      remains an open question. To investigate this, we examined the spatiotemporal
      dynamics of high-density magnetoencephalographic signals, recorded as subjects
      completed a rhyme-judgment task on stimuli varying in the cognitive property of
      lexicality. Our data demonstrate that the time course of occipitotemporal
      cortices discriminates cognitive attributes of orthographic stimuli. The dynamics
      in this brain region may indicate interactive processes unfolding later in the
      time course, when more anterior fronto-temporal circuits are activated by
      semantic correlates of real words.

PMID- 16096786
TI  - Kinetic analysis of the transformation of phthalate esters in a series of
      stoichiometric reactions in anaerobic wastes.
AB  - Phthalates such as dimethyl phthalate, dimethyl terephthalate (DMT), diethyl
      phthalate (DEP), di(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate
      (MEHP) are degraded to varying degrees under anaerobic conditions in waste
      treatment systems. Here we kinetically analyse the enzymatic hydrolyses involved
      and the subsequent stoichiometric reactions. The resulting model indicates that
      the degradation of the alcohols released and the transformation of the phthalic
      acid (PA) result in biphasic kinetics for the methane formation during
      transformation of DMT, DEP and MEHP. The ester hydrolysis and the PA
      transformation to methane appear to be the two rate-limiting steps. The PA
      fermenting bacteria, which have biomass-specific growth rates between 0.04 and
      0.085 day(-1), grow more slowly than the other bacteria involved. Anaerobic
      microorganisms that remove intermediate products during phthalic acid ester
      conversion appear to be important for the efficiency of the ultimate phthalate
      degradation and to be inhibited by elevated hydrogen partial pressures. The model
      was based on (and the simulations corresponded well with) data obtained from
      experimental waste treatment systems.

PMID- 16096787
TI  - Phase I/II dose escalation study of angiotensin 1-7 [A(1-7)] administered before
      and after chemotherapy in patients with newly diagnosed breast cancer.
AB  - PURPOSE: Multilineage cytopenias occur following myelosuppressive chemotherapy.
      Most hematopoietic agents differentiate along a single lineage and fail to
      prevent progressive cytopenias. Angiotensin 1-7 [A(1-7)] is a hematopoietic agent
      that stimulates the proliferation of multipotential and differentiated progenitor
      cells in cultured bone marrow and human cord blood. The purpose of this study was
      to determine the optimal biologic dose and the maximum tolerated dose of A(1-7).
      EXPERIMENTAL DESIGN: This study determined the safety and activity of A(1-7)
      following chemotherapy in patients with breast cancer. Toxicity was assessed by
      administering A(1-7) daily for 7 days followed by a 7-day washout prior to the
      first cycle of chemotherapy. Beginning 2 days after chemotherapy and continuing
      daily for at least 10 days, fifteen patients received five different A(1-7) doses
      and five patients received filgrastim as a comparator group over three cycles of
      chemotherapy. RESULTS: No dose-limiting toxicity was observed following A(1-7).
      The frequency of adverse events was slightly lower in A(1-7) than in filgrastim
      patients. No patient required a chemotherapy modification due to hematologic
      toxicity. There was an apparent differential dose-response sensitivity of the
      various lineages to A(1-7). At a dose of 100 microg/kg, A(1-7) reduced the
      frequency of grade 2-4 thrombocytopenia, anemia, and grade 3-4 lymphopenia as
      compared to filgrastim. CONCLUSION: These data suggest that A(1-7) may be
      beneficial in attenuating multilineage cytopenias following chemotherapy at a
      dose of 100 mug/kg per day.

PMID- 16096788
TI  - CYP1A1 activation of aminoflavone leads to DNA damage in human tumor cell lines.
AB  - PURPOSE: Aminoflavone (5-amino-2,3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1
      benzopyran-4-one; AF; NSC 686288) is a novel anticancer agent with a unique
      pattern of growth inhibitory activity in the National Cancer Institute (NCI) 60
      tumor cell line screen. Phase I clinical trials with AF will begin soon. We
      previously demonstrated extensive metabolism of AF by cytochrome P450 (CYP) 1A1
      and CYP1A2, metabolic activation, formation of irreversible protein and DNA
      adducts and p53 stabilization in sensitive, but not resistant, human tumor cell
      lines treated with AF [9]. The present studies focus on the effects of AF on
      cellular DNA and cellular responses to DNA damage. METHODS: Phosphorylation of
      H2AX in MCF7 cells treated with AF was determined with immunofluorescence. MTS (3
      (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H
      tetrazolium) assays were used to determine the effect of cotreatment with
      caffeine or wortmannin, inhibitors of ataxia-telangiectasia-mutated protein (ATM)
      and ATR (ATM- and rad3-related protein), on the AF IC(50) values for MCF7 cells.
      DNA damage in MCF7 cells treated with AF was determined by alkaline elution. DNA
      topoisomerase complex stabilization was ascertained by the ICE (in vitro complex
      of enzyme) assay. RESULTS: Treatment of sensitive cells with AF resulted in
      phosphorylation of H2AX, a histone 2A variant that is phosphorylated in response
      to DNA damage. AF IC(50) values for MCF7 cells were lowered by cotreatment with
      caffeine or wortmannin, further implicating DNA damage in AF cytotoxicity. There
      was no evidence of DNA-DNA cross-linking in sensitive cells, but protein
      associated single-strand breaks were observed after AF treatment. Although this
      pattern of DNA damage is commonly associated with topoisomerase poisons, there
      was no evidence for AF-induced stabilization of either topoisomerase I- or II-DNA
      complexes. CONCLUSIONS: These studies further implicate DNA damage in the
      cytotoxicity of AF and identify biochemical features of that damage including
      formation of protein-associated single-strand breaks not involving topoisomerase
      I or II.

PMID- 16096789
TI  - Pharmacokinetic changes induced by the volume of chemotherapy solution in
      patients treated with hyperthermic intraperitoneal mitomycin C.
AB  - BACKGROUND: The rationale supporting the use of intraperitoneal chemotherapy in
      peritoneal surface malignancy relates to a large local-regional effect and low
      systemic toxicity. While optimizing the use of this treatment strategy, little
      information regarding the effect of volume of chemotherapy solution is available.
      OBJECTIVE: The goal of this study was to provide data regarding the effect of
      volume of chemotherapy solution on the pharmacokinetics of intraperitoneal
      chemotherapy. Data by which to optimally adjust this parameter during
      intraperitoneal chemotherapy treatments were sought. METHODS: Forty-eight
      patients with peritoneal surface malignancy were treated with hyperthermic
      intraperitoneal mitomycin C chemotherapy after a complete cytoreduction to remove
      all visible evidence of mucinous tumor. The dose of mitomycin C was always 12.5
      mg/m(2) in males and 10 mg/m(2) in females. The first 12 patients were treated
      with 6 l of 1.5% dextrose peritoneal dialysis solution. The next 14 patients were
      treated with 4 l of fluid and then ten patients were treated with 2 l. In the
      last 12 patients the volume of fluid was 1.5 l/m(2) . Blood, peritoneal fluid,
      and urine samples were obtained every 15 min for 90 min; additional blood and
      urine samples were obtained at 120 min. Mitomycin C concentrations, urine
      volumes, and final intraperitoneal fluid volume were obtained. RESULTS: The
      intraperitoneal and the plasma concentrations were highest in the 2-l group, less
      in the 4-l group, and least in the 6-l group. All differences were statistically
      significant. Also, the percent of mitomycin C absorbed decreased significantly
      from 2, to 4, to 6 l of fluid. The area under the curve (AUC) ratio of
      intraperitoneal concentration times time to intravenous concentration times time
      was 27.01+/-4.92 for 2 l, 22.22+/-7.95 for 4 l, and 24.01+/-8.46 for 6 l. These
      differences were not statistically significant. If both the volume of
      chemotherapy solution and the total dose of mitomycin C were determined from the
      body surface area, the pharmacokinetics of intraperitoneal mitomycin C were more
      consistent. CONCLUSIONS: In order to prescribe a uniform treatment for patients
      receiving hyperthermic intraperitoneal mitomycin C, the total dose of the drug
      and the total volume of chemotherapy solution should be determined from the body
      surface area. If the volume of chemotherapy solution is not based on patient body
      surface area, predictions regarding toxicity are less precise.

PMID- 16096790
TI  - Thiolo-, thiono- and dithiocarbonate and thiocarbamate derivatives of
      demethylpenclomedine as novel anticancer agents.
AB  - PURPOSE: The purpose of this investigation was to synthesize a series of thiolo-,
      thiono- and dithiocarbonate and thiocarbamate derivatives of 4
      demethylpenclomedine (DM-PEN), the major plasma metabolite of penclomedine (PEN)
      in patients observed subsequently to be an active antitumor agent and non
      neurotoxic in a rat model, in order to compare their antitumor activity with that
      of DM-PEN. METHODS: Derivatives were prepared from DM-PEN and evaluated in vivo
      against human MX-1 breast tumor xenografts implanted in the mammary fat pad,
      several of which were also evaluated against human brain tumor xenografts.
      RESULTS: Thiolocarbonate and thiocarbamate derivatives were found to be superior
      to DM-PEN against MX-1 tumor and modestly active against glioblastoma.
      CONCLUSION: The activity of the thiolocarbonates and thiocarbamates against human
      tumor xenografts in vivo suggests consideration of these two series of
      derivatives of DM-PEN for clinical development.

PMID- 16096791
TI  - Identification and linkage mapping of the genes for the putative homeodomain
      protein (hox1) and the putative pheromone receptor protein homologue (rcb1) in a
      bipolar basidiomycete, Pholiota nameko.
AB  - In the current studies, we sequenced and characterized the gene for the
      homeodomain protein (hox1) in a bipolar mushroom, Pholiota nameko, which is a
      putative homologue of A mating type genes in the tetrapolar basidiomycete,
      Coprinopsis cinerea. We also sequenced and characterized the gene for the
      pheromone receptor (rcb1) in P. nameko, which is a putative homologue of the B
      mating type genes in C. cinerea. Restriction fragment length polymorphism (RFLP)
      and linkage analyses indicated that the both genes are present as a single locus
      on the different chromosome. Moreover, in P. nameko, the hox1 gene was mapped to
      the A mating type locus in linkage group I. However, rcb1 was not linked to the A
      mating type locus and was mapped to the other linkage group. These results
      strongly suggest that hox1 regulates with incompatibility in the bipolar
      mushroom, and that rcb1 may not affect the mating function in P. nameko. This is
      the first report regarding the structure of the mating type genes in bipolar
      mushrooms.

PMID- 16096792
TI  - Bilateral tibial stress fracture in a young man due to hypercalciuric
      osteoporosis: a case report.
AB  - Osteoporosis is commonly thought of as a disease of postmenopausal women, and
      older men have a lower risk of fracture than women. A stress fracture is an
      overuse injury and an important cause of disability in the athletic population.
      Presented here is a 30-year-old healthy man with pain on the anterior surface of
      the bilateral tibia. He did not communicate any trauma or overuse activity. The
      neurologic and locomotor system examinations were normal. Radiological
      examinations revealed tibial stress fractures in both left and right tibia and he
      had low bone mineral density. Routine hematological tests, bone resorption and
      formation markers were normal, except for hypercalciuria. After analyzing the
      results of these tests, the patient was diagnosed with bilateral tibial stress
      fractures due to hypercalciuric secondary osteoporosis. Osteoporosis should be
      considered in the differential diagnosis of atraumatic insufficiency fractures,
      especially in young healthy adults.

PMID- 16096793
TI  - Impact of pain severity and location on health-related quality of life.
AB  - Despite evidence that persistent pain affects well-being, little is known about
      the relationship of the location of pain to psychological and functional well
      being. To determine whether patients with musculoskeletal disorders (MSD) are
      more likely to be depressed and functionally disabled compared to patients with
      pain at other sites, we conducted a secondary data analysis of the Medical
      Outcome Study--an observational study of adult outpatients with chronic medical
      conditions. Of the 3,360 patients who completed the baseline assessment, 1,237
      (36.8%) had MSD and 2,123 (63.2%) had no MSD. Among patients in the MSD group,
      84.5% reported > or = mild pain as compared to 70% in the no MSD. In multivariate
      analyses, MSD patients were more likely than non-MSD patients to be depressed
      (beta coefficient=-1.9, p=0.008) and functionally disabled (beta coefficient=
      4.4, p<0.0001). However, the impact of MSD was eliminated after controlling for
      pain severity. Regardless of the location of pain, pain severity appears to be an
      important correlate of functional status, both mental and physical.

PMID- 16096794
TI  - Laparoscopic mobilization of testicular vessels: an adjunctive step in
      orchidopexy for impalpable and redo undescended testis in children.
AB  - The testicular position after conventional inguinal orchidopexy for canalicular,
      "peeping" and redo undescended testes may not be satisfactory despite
      retroperitoneal dissection. Laparoscopy allows extensive mobilization of
      testicular vessels to gain additional length. We review our experience of using
      laparoscopic mobilization of testicular vessels (LMTV) in orchidopexy for these
      difficult undescended testes. From January 2003 to May 2004, LMTV was performed
      in 18 boys. The testicular vessels were mobilized from just proximal to the
      internal inguinal ring to the level of caecum and sigmoid colon respectively.
      Fifteen patients had clinically impalpable testes. Diagnostic laparoscopy
      revealed 13 "peeping" and 2 canalicular testes. LMTV was performed together with
      inguinal orchidopexy. There were three cases of redo orchidopexies because of
      unfavourable testicular position after previous surgery. LMTV was performed
      following inguinal dissection. The median follow-up period is 11.7 months.
      Sixteen testes are located at the base of scrotum, and two at mid-scrotum. The
      size is normal in 17 testes, whereas 1 testis is smaller than the contralateral
      one. LMTV is a safe and efficient adjunctive step in orchidopexy for impalpable
      and redo undescended testes.

PMID- 16096795
TI  - Intercellular adhesion molecule (ICAM-1) response after major neonatal surgery.
AB  - Surgical stress induces systemic endocrine-metabolic responses that influence the
      function of endothelial cells (EC) to cause various systemic reactions.
      Intercellular adhesion molecule (ICAM)-1 is an adhesion molecule that plays an
      important role in inflammation, and increased expression of ICAM-1 on EC is a
      reflection of EC activation. In this study, we investigated the ICAM-1 response
      to surgical stress in neonates undergoing major surgery. Fifteen neonates (mean
      age at surgery: 3.5 +/- 1.2 days) were divided into two groups according to
      indications for surgery: Group I: Congenital diaphragmatic hernia without
      persistent pulmonary hypertension (n = 5); Group II: Gastrointestinal surgery [n
      = 10: duodenal atresia (n = 3), intestinal atresia (n = 6), and esophageal
      atresia (n = 1)]. Serum samples were obtained preoperatively, immediately after
      completion of surgery (time zero), and 24, 48, 72, 96, and 120 h after surgery to
      measure ICAM-1 levels using an enzyme-linked immunosorbent assay, C-reactive
      protein (CRP), and white blood cell count (WBC). Postoperative recovery was
      uneventful in all cases. ICAM-1 levels in both groups increased significantly
      within 24 h of surgery (Group I: P = 0.0038, Group II: P = 0.0320). In Group I,
      ICAM-1 peaked 72 h postoperatively while in Group II it continued to rise until
      96 h postoperatively. The difference between peak levels reached was not
      significant. CRP was first detected 24 h postoperatively in both groups and
      continued to increase until 48 h postoperatively. Again, the difference between
      peak levels reached was not significant. No significant changes in WBC were
      observed in either group. We found that ICAM-1 increases in response to surgical
      stress in neonates, although there was no significant difference in levels.
      However, surgical stress as represented by serum ICAM-1 would appear to last
      longer with intestinal surgery than with non-intestinal surgery. Further research
      is required to establish the usefulness of ICAM-1 as an easily detectable
      substance associated with endothelial damage that reflects the host's response to
      major surgical stress.

PMID- 16096796
TI  - Efficacy of urinary sulfated bile acids for diagnosis of bacterial cholangitis in
      biliary atresia.
AB  - This study evaluated the efficacy of measuring urinary sulfated bile acids (USBA)
      for diagnosis of bacterial cholangitis in patients with biliary atresia. Eight
      infants with biliary atresia were recruited. The USBA level was measured when
      they were admitted to hospital with a fever of unknown origin. Clinical
      manifestations and laboratory data were reviewed. The standard USBA value for
      each patient (S-USBA) was defined as the level measured when they had no fever,
      and USBA ratio (R-USBA) was calculated as the USBA level during the febrile
      episode divided by the S-USBA. Then R-USBA values were compared between febrile
      episodes with and without cholangitis to assess the diagnostic ability of USBA.
      Twenty-three febrile episodes occurred in eight patients during a 15-month
      period. Nine episodes were diagnosed as being due to cholangitis, five were due
      to non-cholangitis, and nine were of undetermined origin. The R-USBA value ranged
      from 1.5 to 15.4 during cholangitis episodes and from 0.4 to 1.2 during non
      cholangitis febrile episodes. When fever was of undetermined origin, R-USBA was
      found to be increased during some episodes and not in others. USBA increased
      immediately in patients with cholangitis. The measurement of USBA is a useful non
      invasive test for cholangitis in patients with biliary atresia who had undergone
      Kasai's operation.

PMID- 16096798
TI  - Navigated intraoperative analysis of lower limb alignment.
AB  - INTRODUCTION: Accurate intraoperative assessment of lower limb alignment is
      crucial for the treatment of long bone fractures, implantation of knee
      arthroplasties and correction of deformities. During orthopaedic surgery, exact
      real time control of the mechanical axis is strongly desirable. The aim of this
      study was to compare conventional intraoperative analysis of the mechanical axis
      by the cable method with continuous, 3-dimensional imaging with a navigation
      system. MATERIALS AND METHODS: Twenty legs of fresh human cadaver were randomly
      assigned to conventional analysis with the cable method (n = 10) or navigated
      analysis with a fluoroscopy based navigation system (n = 10). The intersection of
      the mechanical axis with the tibia plateau was presented as percentage of the
      tibia plateau (beginning with 0% at the medial border and ending with 100%
      laterally). CT-scans were performed for all legs and the CT-values of the
      mechanical axis were compared to the measurements after cable method and
      navigation. Furthermore, the radiation time and dose area product of both groups
      for single analysis of the mechanical axis was compared. RESULTS: Conventional
      evaluation of the mechanical axis by the cable method showed 6.0+/-3.1%
      difference compared to the analysis by CT. In the navigated group the difference
      was 2.6+/-1.8% (P = 0.008). Radiation time and dose area product were highly
      significantly lower after conventional measurement. CONCLUSIONS: Navigated
      intraoperative evaluation of the mechanical axis offers increased accuracy
      compared to conventional intraoperative analysis. Furthermore, navigation
      provides continuous control not only of the mechanical axis, but also of the
      sagittal and transverse plane. Using the cable method, radiation exposure depends
      on the number of measurements and is lower compared to the navigation system for
      single intraoperative analysis of the mechanical axis, but may be higher in case
      of repeated intraoperative measurements.

PMID- 16096797
TI  - Does pneumoperitoneum always require laparotomy? Report of six cases and review
      of the literature.
AB  - The presence of intraperitoneal free air signals perforation of a hollow viscus
      in over 90% of the patients. Rarely, however, the presence of pneumoperitoneum
      may not indicate an intra-abdominal perforation and thus may not require
      laparotomy. This condition, which poses a dilemma to the surgeon faced with this
      problem, is termed "nonsurgical", "spontaneous" or "idiopathic" pneumoperitoneum.
      Six cases of nonsurgical pneumoperitoneum admitted over a 2-year period to our
      institution are reported, and the etiological mechanisms and the pathophysiology
      of the appearance of intra-abdominal free gas are reviewed. Two of the six
      children with nonsurgical pneumoperitoneum underwent exploratory laparotomy when
      clinical examination suggested an acute abdomen; no intra-abdominal pathology was
      documented in one of these patients. In the other children, malrotation was
      found. Four patients, on ventilatory support, were managed conservatively after
      performing a diagnostic peritoneal lavage and/or contrast studies those were
      negative. An appreciation of the condition and its likely etiological factors
      should improve awareness and possibly reduce the imperative to perform emergency
      laparotomy on an otherwise well patient with an unexplained pneumoperitoneum.

PMID- 16096799
TI  - Morphologic features of the acetabulum.
AB  - INTRODUCTION: The embryology and development of the hip joint are complex. The
      acetabulum is not always of the same shape, width, or depth. Minor anatomical
      abnormalities in the acetabular shape, joint congruences are frequent.
      Controversies still exist on the importance of these variations and help to
      prevent problems following in surgical procedures such as acetabular
      reconstruction and femoracetabular impingement. MATERIAL AND METHODS: The aim of
      this study is to provide the location of the unusual facets, the acetabular
      point, and the anterior ridge of the acetabulum based on a morphological study of
      human pelvic bones. Morphologic features of the acetabulum, particularly
      determination of unusual facets, were studied in 226 human coxal bones. RESULTS:
      In adult coxal bones the acetabular fossa has an irregular clover-leaf shape, the
      superior lobe being smaller than the anterior and the posterior lobes. Measured
      lunate surface area varied between 14.5 and 30.5 cm2. A smooth unusual facet was
      found anteroinferior to the lunate surface in 62 acetabulums. Measured along the
      long axis, its size varied between 11 and 17 mm. Three different shapes of the
      unusual facet were as follows: oval (32.26%), piriform (45.16%), and elongated
      (22.58%). The prevalence of the piriform facet shape was higher in males. In
      59.68% of the bones it extended to the superior ramus of the pubis, and in the
      remaining 40.32% it was limited within the acetabular margin. It is postulated
      that this facet could be a consequence of a particular posture, which results in
      traction of the ligaments attached to this area. Four distinct configurations
      were identified relative to the anterior acetabular ridge. The majority 98
      (43.36%) were curved; 64 (28.33%) were angular; 37 (16.37%) were irregular; and
      27 (11.94%) were straight. CONCLUSION: There have been no reports on details such
      as unusual facets, acetabular point, and anterior ridge of the acetabulum in a
      single research. These findings will be of help in planning reorientation
      procedures, using spikes, screws, and press-fitting for fixation.

PMID- 16096800
TI  - Identification of differentially expressed genes HSPC016 in dermal papilla cells
      with aggregative behavior.
AB  - The dermal papilla plays pivotal roles in hair follicle cycle and dermal papilla
      cells (DPCs) with aggregative behavior have more obviously inductive ability. In
      the present study, the suppression subtractive hybridization method was employed
      to identify the differentially expressed genes in dermal papillae cells with
      aggregative behavior. Following mRNA isolation of DPC with and without
      aggregative behavior, cDNA of both populations were prepared and subtracted by
      suppression PCR. Sequencing of enriched cDNAs identified five genes
      differentially expressed including capping protein, paladin, and vascular
      endothelial growth factor. Interestingly, HSPC016, first cloned from CD34+
      hematopoietic stem/progenitor cells (HSPC), was identified by SSH, cDNA dot blot
      and Northern blot, which showed that this gene was differentially expressed in
      DPC with aggregative behavior. The full-length cDNA of HSPC016 was shown to be
      366 bp, and the possible function of HSPC016 related to transcriptional
      regulation.

PMID- 16096801
TI  - Single-minded, Dmef2, Pointed, and Su(H) act on identified regulatory sequences
      of the roughest gene in Drosophila melanogaster.
AB  - Roughest (Rst) is a cell adhesion molecule of the immunoglobulin superfamily that
      has multiple and diverse functions during the development of Drosophila
      melanogaster. The pleiotropic action of Rst is reflected by its complex and
      dynamic expression during the development of Drosophila. By an enhancer detection
      screen, we previously identified several cis-regulatory modules that mediate
      specific expression of the roughest gene in Drosophila developmental processes.
      To identify trans-regulators of rst expression, we used the Gal4/UAS system to
      screen for factors that were sufficient to activate Rst expression when
      ectopically expressed. By this method we identified the transcription factors
      Single-minded, Pointed.P1, and Su(H)-VP16. Furthermore, we showed that these
      factors and, in addition, Dmef2 are able to ectopically activate rst expression
      via the previously described rst cis-regulatory modules. This fact and the use of
      mutant analysis allocates the action of the transcription factors to specific
      developmental contexts. In the case of Sim, we could show that it regulates rst
      expression in the embryonic midline, but not in the optic lobes. Mutagenesis of
      Sim consensus binding sites in the regulatory module required for rst expression
      in the embryonic midline, abolished rst expression; indicating that the
      regulation of rst by Sim is direct.

PMID- 16096802
TI  - kitb, a second zebrafish ortholog of mouse Kit.
AB  - The large numbers of duplicated pairs of genes in zebrafish compared to their
      mammalian counterparts has lead to the notion that expression of zebrafish co
      orthologous pairs in some cases can together describe the expression of their
      mammalian counterpart. Here, we explore this notion by identification and
      analysis of a second zebrafish ortholog of the mammalian Kit receptor tyrosine
      kinase (kitb). We show that in embryos, kitb is expressed in a non-overlapping
      pattern to that of kita, in the anterior ventral mesoderm, Rohon-beardRohon-Beard
      neurons, the otic vesicle, and trigeminal ganglia. The expression pattern of kita
      and kitb in zebrafish together approximates that of Kit in mouse, with the
      exception that neither zebrafish kit gene is expressed in primordial germ cells,
      a site of kit expression in the mouse embryo. In addition, zebrafish kita is
      expressed in a site of zebrafish primitive hematopoiesis but not required for
      blood development, and we fail to detect kitb expression in sites of zebrafish
      hematopoiesis. Thus, the expression and function of zebrafish kit genes cannot be
      described as a simple partition of the expression and function of mouse Kit. We
      discuss the possibility that these unaccounted for expression domains and
      functions are derived from more ancestral gene duplications and partitioning
      instead of the relatively recent teleost teleost-specific duplication.

PMID- 16096803
TI  - Direct observation of multiple protonation states in recombinant human purple
      acid phosphatase.
AB  - To date, most spectroscopic studies on mammalian purple acid phosphatases (PAPs)
      have been performed at a single pH, typically pH 5. The catalytic activity of
      these enzymes is, however, pH dependent, with optimal pH values of 5.5-6.2
      (depending on the form). For example, the pH optimum of PAPs isolated as single
      polypeptides is around pH 5.5, which is substantially lower that of
      proteolytically cleaved PAPs (ca. pH 6.2). In addition, the catalytic activity of
      single polypeptide PAPs at their optimal pH values is four to fivefold lower than
      that of the proteolytically cleaved enzymes. In order to elucidate the chemical
      basis for the pH dependence of these enzymes, the spectroscopic properties of
      both the single polypeptide and proteolytically cleaved forms of recombinant
      human PAP (recHPAP) and their complexes with inhibitory anions have been examined
      over the pH range 4 to 8. The EPR spectra of both forms of recHPAP are pH
      dependent and show the presence of three species: an inactive low pH form (pH<pK(
      a,1)), an active form (pK( a,1)<pH<pK( a,2)), and an inactive high pH form
      (pH>pK( a,2)). The pK( a,1) values observed by EPR for the single polypeptide and
      proteolytically cleaved forms are similar to those previously observed in
      kinetics studies. The spectroscopic properties of the enzyme-phosphate complex
      (which should mimic the enzyme-substrate complex), the enzyme-fluoride complex,
      and the enzyme-fluoride-phosphate complex (which should mimic the ternary enzyme
      substrate-hydroxide complex) were also examined. EPR spectra show that phosphate
      binds to the diiron center of the proteolytically cleaved form of the enzyme, but
      not to that of the single polypeptide form. EPR spectra also show that fluoride
      binds only to the low pH form of the enzymes, in which it presumably replaces a
      coordinated water molecule. The binding of fluoride and phosphate to form a
      ternary complex appears to be cooperative.

PMID- 16096804
TI  - Interactions in pseudorotoxanes based on crown ether-secondary ammonium motifs. A
      theoretical study.
AB  - A theoretical analysis of the nature of the interactions in dibenzo[24]crown-8
      (DB24C8)-n-dibutylammonium (DBM)--pseudorotaxane complex at the MP2 and DFT
      levels shows that the main contribution to the binding energy is the
      electrostatic interaction with moderate (20-25%) correlation stabilization. The
      total binding energy in the DB24C8-DBM complex represents a sum of the binding
      energies of two NH-O and one CH-O hydrogen bonds and the latter constitutes about
      25% of the total interaction energy, giving the total binding energy of -41.2
      kcal mol(-1) at the BHandHLYP/6-311 + + G** level. Deprotonation of the DB24C8
      DBM complex reduces the binding energy by some 50 kcal mol(-1), giving metastable
      complexes DB24C8-DBA-1 or DB24C8-DBA-2, which will dissociate to give free crown
      ether and n-dibutylamine because of the strong exchange repulsion that prevails
      in neutral complexes.

PMID- 16096805
TI  - A fold-recognition approach to loop modeling.
AB  - A novel approach is proposed for modeling loop regions in proteins. In this
      approach, a prerequisite sequence-structure alignment is examined for regions
      where the target sequence is not covered by the structural template. These
      regions, extended with a number of residues from adjacent stem regions, are
      submitted to fold recognition. The alignments produced by fold recognition are
      integrated into the initial alignment to create an alignment between the target
      sequence and several structures, where gaps in the main structural template are
      covered by local structural templates. This one-to-many (1:N) alignment is used
      to create a protein model by existing protein-modeling techniques. Several
      alternative approaches were evaluated using a set of ten proteins. One approach
      was selected and evaluated using another set of 31 proteins. The most promising
      result was for gap regions not located at the C-terminus or N-terminus of a
      protein, where the method produced an average RMSD 12% lower than the loop
      modeling provided with the program MODELLER. This improvement is shown to be
      statistically significant.

PMID- 16096806
TI  - Molecular models of protein kinase 6 from Plasmodium falciparum.
AB  - Cyclin-dependent kinases (CDKs) have been identified as potential targets for
      development of drugs, mainly against cancer. These studies generated a vast
      library of chemical inhibitors of CDKs, and some of these molecules can also
      inhibit kinases identified in the Plasmodium falciparum genome. Here we describe
      structural models for Protein Kinase 6 from P. falciparum (PfPK6) complexed with
      Roscovitine and Olomoucine. These models show clear structural evidence for
      differences observed in the inhibition, and may help designing inhibitors for
      PfPK6 generating new potential drugs against malaria.

PMID- 16096807
TI  - Comparison between Generalized-Born and Poisson-Boltzmann methods in physics
      based scoring functions for protein structure prediction.
AB  - Continuum solvent models such as Generalized-Born and Poisson-Boltzmann methods
      hold the promise to treat solvation effect efficiently and to enable rapid
      scoring of protein structures when they are combined with physics-based energy
      functions. Yet, direct comparison of these two approaches on large protein data
      set is lacking. Building on our previous work with a scoring function based on a
      Generalized-Born (GB) solvation model, and short molecular-dynamics simulations,
      we further extended the scoring function to compare with the MM-PBSA method to
      treat the solvent effect. We benchmarked this scoring function against seven
      publicly available decoy sets. We found that, somewhat surprisingly, the results
      of MM-PBSA approach are comparable to the previous GB-based scoring function. We
      also discussed the effect to the scoring function accuracy due to presence of
      large ligands and ions in some native structures of the decoy sets.

PMID- 16096808
TI  - In vitro imaging of single living human umbilical vein endothelial cells with a
      clinical 3.0-T MRI scanner.
AB  - Iron oxide-labelled, single, living human umbilical vein endothelial cells
      (HUVECs) were imaged over time in vitro using a clinical 3.0-T magnetic resonance
      (MR) microscopy system. Labelling efficiency, toxicity, cell viability,
      proliferation and differentiation were assessed using flow cytometry, magnetic
      cell sorting and a phenanthroline assay. MR images were compared with normal
      light and fluorescence microscopy. Efficient uptake of iron oxide into HUVECs was
      shown, although with higher label uptake dose-dependent cytotoxic effects were
      observed, affecting cell viability. For MR imaging, a T2* weighted three
      dimensional protocol was used with in-plane resolution of 39 x 48 microm2 and 100
      microm slices with a scan time of 13 min. MRI could detect living cells in
      standard culture dishes at single-cell resolution, although label loss was
      observed that corresponded with the intracellular iron measurements. MR
      microscopy using iron oxide labels is a promising tool for studying HUVEC
      migration and cell biology in vitro and in vivo, but possible toxic effects of
      label uptake and loss of label over time should be taken into account.

PMID- 16096809
TI  - Long term disability and social status change after Guillain-Barre syndrome.
AB  - OBJECTIVE: Even if the majority of patients with Guillain-Barre syndrome (GBS)
      have a favourable functional outcome some residual motor and sensory signs and
      symptoms may remain. The aim of this study was to evaluate the long-term effect
      of GBS on daily life,working activities, hobbies and social status and the
      presence of residual symptoms. PATIENTS AND METHODS: Seventy patients with GBS
      enrolled in a case-control study were examined. Information on signs or symptoms
      during the acute phase of the disease was retrieved from medical records and an
      ad-hoc questionnaire administered during hospitalization. Patients were
      interviewed by phone 3 to 5 years after disease onset about residual symptoms and
      changes in daily living. Disability and handicap were assessed using the Hughes,
      Rankin and Rotterdam 9-items scale. RESULTS: At follow-up 45 patients (64 %) made
      a complete functional recovery; 19 patients (27%) had some minor limitations in
      daily life although they were able to perform all their activities independently
      while 6 (9 %) needed aid for some hours or continuously during the day. Nineteen
      patients (27 %) had, however, to make substantial changes in their job, hobbies
      or social activities. There was no significant correlation between clinical and
      laboratory features during the acute phase of GBS and outcome. CONCLUSIONS:
      Although over 90% of our GBS patients had a more or less complete functional
      recovery, almost 30% of them had to make substantial changes in daily life. These
      findings indicate that GBS still has a significant impact on patients' life which
      may go beyond their residual disability or impairment. Treatment of GBS should
      not be only aimed at improving patients' disability but also at limiting the
      impact of the disease on their social life.

PMID- 16096810
TI  - Interaction of loci within the HLA region influences multiple sclerosis course in
      the Sardinian population.
AB  - We examined the influence of alleles at the HLA loci, previously found to be
      associated with multiple sclerosis (MS) in Sardinia, on the clinical course of
      the disease in 835 relapsing (R) and 100 primary progressive (PP) patients.
      Multivariate analysis was carried out on predisposing 0301 or non-associated DPB1
      alleles, susceptible or non-associated DRB1-DQB1 haplotypes, both predisposing
      and non-predisposing, and negatively and non-negatively associated D6S1683
      alleles, taking interaction between them into account. Intra-patient analysis
      showed that the presence of the susceptible or protective D6S1683 allele
      interacting with predisposing DP 0301 modulated risk of PP disease. These
      findings suggest that a locus telomeric to HLA class I exerts an effect on
      alleles at the DPB1 locus in modulating disease course.

PMID- 16096811
TI  - Four novel connexin 32 mutations in X-linked Charcot-Marie-Tooth disease with
      phenotypic variability.

PMID- 16096812
TI  - Hereditary hemochromatosis and movement disorders: the still controversial
      relationship. Response to Russo et al. in J Neurol (2004) 251:849-852.

PMID- 16096814
TI  - Neuropsychological evidence for separating components of visuo-spatial working
      memory.
AB  - There is increasing evidence to support the idea that visuo-spatial working
      memory can be segregated into separate cognitive subsystems. However, the nature
      of these systems remains unclear. In this paper we report data from two brain
      injured patients suggesting that information about visual appearance is retained
      in a different subsystem from information about spatial location, and that this
      differential processing can be observed when the style of presentation
      (sequential or simultaneous) is controlled.

PMID- 16096813
TI  - Cholesteryl ester transfer protein (CETP) polymorphism modifies the Alzheimer's
      disease risk associated with APOE epsilon4 allele.
AB  - Cholesterol regulates the production of amyloid beta (Abeta), which is central to
      the pathogenesis of Alzheimer's disease (AD), with high cellular cholesterol
      promoting and low cellular cholesterol reducing Abeta in vitro and in vivo. High
      density lipoprotein (HDL) plays a central role in the removal of excess
      cholesterol from cells, and cholesteryl ester transfer protein (CETP) is a
      crucial protein involved in the regulation of HDL levels. Two common
      polymorphisms in the promoter region (C-629A) and exon 14 I405V of the CETP gene
      are associated with CETP activity and HDL levels. To investigate if these
      sequence variants in CETP might be of importance in mediating susceptibility to
      AD, independently or in concert with apolipoprotein E (APOE) epsilon4 allele, we
      studied a sample of 286 Spanish AD patients and 315 healthy controls. In APOE
      epsilon4 carriers, homozygous for the CETP (-629) A allele had approximately a
      three times lower risk of developing AD (odds ratio 2.33, 95% CI 1.01-5.37), than
      homozygous and heterozygous carriers of the CETP (-629) C allele (odds ratio
      7.12, 95% CI 4.51-11.24, P for APOE epsilon4/CETP (-629) AA genotype interaction
      < 0.001). Our data suggest that CETP behaves as a modifier gene of the AD risk
      associated with the APOE epsilon4 allele, possibly through modulation of brain
      cholesterol metabolism.

PMID- 16096815
TI  - The effect of quetiapine in psychotic Parkinsonian patients with and without
      dementia. An open-labeled study utilizing a structured interview.
AB  - OBJECTIVES: We studied the effect of quetiapine in drug induced psychosis (DIP)
      in Parkinson's disease (PD) patients with dementia (PDDEM) and without dementia
      (PDNODEM) in a 6-month open study. METHODS: Thirty five consecutive PD patients
      with DIP (19 of them demented [DSMIV criteria]) were examined. Assessment
      included Mini-Mental State Examination (MMSE), UPDRS (motor part), Brief
      Psychiatric Rating Scale (BPRS), Clinical Global Improvement Scale (CGIS) and
      Hamilton test (for depression). Quetiapine was administered in a flexible dose 25
      600 mg daily. Out of the 35 patients included in the study, 24 completed
      treatment with quetiapine (14 demented and 10 without dementia). Treatment was
      stopped in 11 patients (5 demented). RESULTS: Intention to treat patient (ITT)
      analysis did not show a significant quetiapine effect (BPRS), although in about
      30% a good outcome was reported by the family (CGIS). Among the patients who
      completed the study (n = 24), in the PDNODEM group (n = 10) BPRS improved almost
      significantly (p = 0.06) while in the PDDEM group the BPRS did not change.
      According to the CGIS, a good improvement was observed in 50% of the PDDEM group
      (7/14) and 40% of the PDNODEM group (4/10). Motor features of PD patients
      worsened mildly (p = 0.05) in the PDDEM group. CONCLUSION: In this open trial,
      quetiapine was not beneficial in the ITT group using the BPRS, although families
      reported improvement in about 30% of patients (CGIS). Among patients who
      completed the study, quetiapine was more effective in the PDNODEM group. A double
      blind study with quetiapine is required.

PMID- 16096816
TI  - Subcortical Right Parietal AVM Rotational vertigo and caloric stimulation fMRI
      support a parietal representation of vestibular input.

PMID- 16096817
TI  - The place of perceptual analysis of dysarthria in the differential diagnosis of
      corticobasal degeneration and Parkinson's disease.
AB  - OBJECTIVE: To characterize the dysarthria in patients with corticobasal
      degeneration (CBD) and determine if analysis of speech in isolation helps to
      distinguish CBD patients from patients with Parkinson's disease (PD). METHODS: 60
      subjects were assessed by means of perceptual analysis of speech: 15 patients
      with CBD, 15 patients with PD and 30 control subjects. A detailed profile was
      furnished with the help of 33 perceptual items. A global perceptual approach was
      used to classify patients by judges blind to the medical diagnosis. Rating scales
      were adapted to quantify the degree of spasticity and hypokinesia in the speech
      of each patient. RESULTS: Dysarthria was frequent in CBD even though it remained
      mild for a long period of time. Group analysis revealed the importance of
      temporal errors of speech control in CBD patients while voice disturbances were
      most frequent in PD patients. However, attempts to classify patients according to
      global perceptual analysis remained below a reasonable level of clinical
      acceptability. Finally, even though the widespread neuropathological changes
      suggest that deviant speech dimensions of several types of dysarthria might be
      found in CBD, evidence for a mixed dysarthria with presence of spastic elements
      could not be established. CONCLUSION: The findings support the view that even
      though perceptual analysis is mandatory in the management of dysarthric patients,
      it does not help in the clinical differential diagnosis of CBD.

PMID- 16096818
TI  - Role of hypokinesia and bradykinesia in gait disturbances in Huntington's
      disease: a biomechanical study.
AB  - OBJECTIVE: To evaluate specific patterns of locomotion in Huntington's disease
      (HD) and notably the respective roles of hypokinesia (i. e. a decrease in the
      amplitude of movement) and bradykinesia (i. e. difficulty in executing a
      movement, slowness) in gait disturbance. METHODS: Kinematic, spatial (stride
      length, speed), temporal (cadence, speed, and stride time) and angular gait
      parameters (joint ankle range) were recorded in 15 early-stage HD patients by
      means of a video motion analysis system and then compared with 15 controls and 15
      Parkinson's disease (PD) patients. Hypokinesia was studied in terms of both
      spatial (decrease in stride length) and angular gait parameters (decrease in
      joint ankle range), whereas hyperkinesia was characterized by an increase in
      joint ankle range. Bradykinesia (defined by a decrease in gait velocity) was also
      assessed in terms of temporal parameters (cadence, stride time). We studied the
      influence of clinical symptoms (motor dysfunction, chorea, overall disability and
      cognitive impairment) and the CAG repeat number on gait abnormalities. RESULTS:
      we observed a clear decrease in gait speed, a decrease in cadence and an increase
      in stride time (i. e. bradykinesia) for HD, with significant intra-individual
      variability. Cadence remained normal in PD. In HD, there was no evidence for a
      clear decrease in stride length, although the latter is a characteristic feature
      of hypokinetic gait (such as that observed in PD). Angle analysis revealed the
      coexistence of hyperkinesia and hypokinesia in HD, which thus participate in gait
      abnormalities. Gait speed in HD was correlated to the motor part of the UHDRS.
      CONCLUSION: Gait in HD is mainly characterized by a timing disorder: bradykinesia
      was present, with severe intra-individual variability in temporal gait
      parameters.

PMID- 16096819
TI  - Effect of physical countermaneuvers on orthostatic hypotension in familial
      dysautonomia.
AB  - Familial dysautonomia (FD) patients frequently experience debilitating
      orthostatic hypotension. Since physical countermaneuvers can increase blood
      pressure (BP) in other groups of patients with orthostatic hypotension, we
      evaluated the effectiveness of countermaneuvers in FD patients. In 17 FD patients
      (26.4 +/- 12.4 years, eight female), we monitored heart rate (HR), blood pressure
      (BP), cardiac output (CO), total peripheral resistance (TPR) and calf volume
      while supine, during standing and during application of four countermaneuvers:
      bending forward, squatting, leg crossing, and abdominal compression using an
      inflatable belt. Countermaneuvers were initiated after standing up,when systolic
      BP had fallen by 40mmHg or diastolic BP by 30mmHg or presyncope had occurred.
      During active standing, blood pressure and TPR decreased, calf volume increased
      but CO remained stable. Mean BP increased significantly during bending forward
      (by 20.0 (17 - 28.5) mmHg; P = 0.005) (median (25(th) - 75(th) quartile)),
      squatting (by 50.8 (33.5 - 56) mmHg; P = 0.002), and abdominal compression (by
      5.8 (-1 - 34.7) mmHg; P = 0.04) - but not during leg-crossing. Squatting and
      abdominal compression also induced a significant increase in CO (by 18.1 (-1.3 -
      47.9) % during squatting (P = 0.02) and by 7.6 (0.4 - 19.6) % during abdominal
      compression (P=0.014)). HR did not change significantly during the
      countermaneuvers. TPR increased significantly only during squatting (by 37.2
      (11.8 - 48.2) %; P = 0.01). However, orthopedic problems or ataxia prevented
      several patients from performing some of the countermaneuvers. Additionally, many
      patients required assistance with the maneuvers. Squatting, bending forward and
      abdominal compression can improve orthostatic BP in FD patients, which is
      achieved mainly by an increased cardiac output. Squatting has the greatest effect
      on orthostatic blood pressure in FD patients. Suitability and effectiveness of a
      specific countermaneuver depends on the orthopedic or neurological complications
      of each FD patient and must be individually tested before a therapeutic
      recommendation can be given.

PMID- 16096820
TI  - Acetylcholine esterase inhibitor donepezil improves dynamic cerebrovascular
      regulation in Alzheimer patients.
AB  - BACKGROUND: Alzheimer's disease (AD) leads to a degeneration of the nucleus
      basalis of Meynert and thus to decreased cholinergic tonus in the brain. The
      transcription of endothelial nitric oxide synthase depends on an adequate
      cholinergic innervation of microvessels and vasoregulative abnormalities have
      been reported in AD. We investigated activation-flow coupling to study the role
      of acetylcholine esterase inhibition (AChEI) on vasoregulative function. METHODS:
      A functional transcranial Doppler approach was used to measure the visually
      evoked flow velocity response in the posterior cerebral artery in AD patients who
      had no vascular risk factors. The diagnosis of AD was made according to the
      ICD10/DSMIIIR-criteria. After baseline recording the effect of four weeks 5mg
      donepezil and then four weeks 10 mg was investigated. Doppler data were evaluated
      with a control system approach to obtain dynamic properties of vasoregulation and
      were compared with a healthy control group. RESULTS: AD patients showed an
      increased damping (0.64 +/- 0.2; p = 0.007 vs. control) in evoked responses and
      lower resting flow velocity levels (40 +/- 13 cm/s; p = 0.06 vs. control), which
      were restored in a dose-dependent manner under AChEI (0.4 +/- 0.2; 44 +/- 11
      cm/s). CONCLUSIONS: AD is associated with a functional vasoregulative deficit
      possibly due to decreased levels of the endothelial nitric oxide synthase.
      Augmenting levels with AChEI normalized flow regulation possibly leading to a
      better blood supply to active neurons.

PMID- 16096821
TI  - Acute encephalopathy due to glycerol over-consumption.

PMID- 16096822
TI  - Delayed spinal decompression sickness after air flight.

PMID- 16096824
TI  - Gaseous distention of the hypopharynx and cervical esophagus with nasal CPAP: a
      mimicker of pharyngeal perforation and esophageal atresia.
AB  - BACKGROUND: Nasal continuous positive airway pressure (CPAP) has been used since
      1975 as the initial treatment for respiratory distress syndrome (RDS) in very
      premature infants. Gaseous distention of the abdomen (CPAP belly) is a common
      secondary effect of CPAP. Gaseous distention of the hypopharynx is also common.
      OBJECTIVE: To determine the incidence of hypopharyngeal distention in infants on
      CPAP. MATERIALS AND METHODS: We performed a retrospective review of the chest
      radiographs of 57 premature infants treated with CPAP during a 4-week period to
      find the presence and degree of hypopharyngeal distention. RESULTS: Of the 57
      radiographs, 14 (25%) revealed gaseous distention of the hypopharynx and/or
      cervical esophagus. On occasion, this raised concern for pharyngeal perforation
      or esophageal atresia. CONCLUSION: Awareness that CPAP-related hypopharyngeal
      distention is common should help radiologists avoid erroneous consideration of
      esophageal atresia or hypopharyngeal perforation.

PMID- 16096823
TI  - Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type
      2 diabetic patients.
AB  - AIMS/HYPOTHESIS: In the present study, we investigated the consequences of
      adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2
      diabetic patients. MATERIALS AND METHODS: We studied ten type 2 diabetic patients
      under the following conditions: (1) at rest; (2) during 60 min of cycling
      exercise at 50% of maximal workload capacity and subsequent recovery. Studies
      were done under normal, fasting conditions (control trial: CON) and following
      administration of a nicotinic acid analogue (low plasma non-esterified fatty acid
      trial: LFA). Continuous [U-13C]palmitate and [6,6 -2H2]glucose infusions were
      applied to quantify plasma NEFA and glucose oxidation rates, and to estimate
      intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were
      collected before and after exercise to determine net changes in lipid and
      glycogen content specific to muscle fibre type. RESULTS: Following administration
      of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was
      effectively reduced, resulting in lower NEFA concentrations in the LFA trial
      (p<0.001). Plasma NEFA oxidation rates were substantially reduced at rest, during
      exercise and subsequent recovery in the LFA trial. The lower plasma NEFA
      oxidation rates were compensated by an increase in IMTG and endogenous
      carbohydrate use (p<0.05). Plasma glucose disposal rates did not differ between
      trials. In accordance with the tracer data, a greater net decline in type I
      muscle fibre lipid content was observed following exercise in the LFA trial
      (p<0.05). CONCLUSIONS/INTERPRETATION: This study shows that plasma NEFA
      availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in
      combination with exercise, could be an effective means of augmenting
      intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight
      fasted state.

PMID- 16096826
TI  - Ileocolic intussusception mimicking the imaging appearance of midgut volvulus as
      a result of extrinsic duodenal obstruction.
AB  - Duodenal obstruction caused by ileocolic intussusception in the absence of
      intestinal malrotation is extremely rare. We present and discuss the imaging
      findings in an infant with an intussusception secondary to a duplication cyst in
      whom sonography also showed inversion of the orientation of the mesenteric
      vessels and a distended stomach. A contrast medium study revealed a proximal
      duodenal obstruction with a beak appearance suggestive of midgut volvulus. At
      surgery, an ileocolic intussusception causing duodenal obstruction without
      concomitant malrotation or volvulus was found. The combination of duodenal
      obstruction and abnormal relationship of the mesenteric vessels as a result of
      ileocolic intussusception has not previously been reported in the literature.

PMID- 16096825
TI  - MRI diagnosis of isolated origin of the left subclavian artery from the left
      pulmonary artery.
AB  - Right aortic arch with isolation of the left subclavian artery is a rare
      disorder. In this entity, the left subclavian artery has its origin from the
      pulmonary artery via the ductus arteriosus. We report an infant with an
      unbalanced atrioventricular septal defect, right aortic arch, bilateral ductus
      arteriosi and an isolated left subclavian artery. This infant also had chromosome
      22q11 deletion. The origin and course of the isolated subclavian artery were well
      demonstrated using contrast-enhanced 3-D magnetic resonance angiography. This non
      invasive diagnostic modality can accurately reveal detailed mediastinal vascular
      anatomy in a young infant and allows diagnosis of aberrant vascular connections.

PMID- 16096827
TI  - Extensive pneumothorax, pneumomediastinum and surgical emphysema as a
      complication of bleomycin therapy.
AB  - Bleomycin is a commonly used chemotherapeutic agent and one of the commonest
      cytotoxic drugs leading to pulmonary parenchymal damage. It generally leads to
      interstitial pneumonitis and fibrosis, hypersensitivity reactions and acute
      respiratory distress syndrome. We describe an 8-year-old boy who, following
      prolonged bleomycin therapy, demonstrated extensive air dissection and
      extrapulmonary air, an unusual and fatal complication.

PMID- 16096828
TI  - Spontaneous gastric perforation in a neonate presenting with massive
      hydroperitoneum.
AB  - We report the imaging findings in a case of neonatal spontaneous gastric
      perforation presenting as massive hydroperitoneum rather than pneumoperitoneum.
      Plain abdominal radiography showed a diffuse ground-glass opacity with paucity of
      bowel gas. Subsequent ultrasonography demonstrated numerous echogenic peritoneal
      fluid collections containing echogenic debris shown at surgery to be due to milk
      and bile.

PMID- 16096829
TI  - Human gene therapy and imaging: cardiology.
AB  - This review discusses the basics of cardiovascular gene therapy, the results of
      recent human clinical trials, and the rapid progress in imaging techniques in
      cardiology. Improved understanding of the molecular and genetic basis of coronary
      heart disease has made gene therapy a potential new alternative for the treatment
      of cardiovascular diseases. Experimental studies have established the proof-of
      principle that gene transfer to the cardiovascular system can achieve therapeutic
      effects. First human clinical trials provided initial evidence of feasibility and
      safety of cardiovascular gene therapy. However, phase II/III clinical trials have
      so far been rather disappointing and one of the major problems in cardiovascular
      gene therapy has been the inability to verify gene expression in the target
      tissue. New imaging techniques could significantly contribute to the development
      of better gene therapeutic approaches. Although the exact choice of imaging
      modality will depend on the biological question asked, further improvement in
      image resolution and detection sensitivity will be needed for all modalities as
      we move from imaging of organs and tissues to imaging of cells and genes.

PMID- 16096830
TI  - Transdifferentiation of mesenchymal stem cells into cardiomyocytes by direct cell
      to-cell contact with neonatal cardiomyocyte but not adult cardiomyocytes.
AB  - Recent studies have demonstrated that direct cell-to-cell interaction is one of
      the microenvironment factors for transdifferentiation of adult stem cells into
      cardiomyocytes. We investigated whether transdifferentiation of mesenchymal stem
      cells (MSCs) into cardiomyocytes was dependent on developmental stages of
      cocultured cardiomyocytes, and direct cell-to-cell interaction was essential for
      transdifferentiation. MSCs were isolated from adult rat and cocultured in four
      different ways: (1) with neonatal cardiomyocytes, (2) with adult cardiomyocytes,
      (3) with neonatal cardiomyocytes on the cell culture inserts, and (4) with the
      conditioned medium from neonatal cardiomyocytes. After 5 days of coculture with
      neonatal cardiomyocytes, 9.40+/-1.15% of 1,1'-dioctadecyl-1-3,3,3',3'
      tetramethylindocarbocyanine perchlorate labeled MSCs expressed sarcomeric-alpha
      actinin. Immunocytochemistry showed that only these MSCs expressed the cardiac
      markers and were not observed with other coculture condition as well as
      conditioned medium. Calcein-AM labeling of cardiomyocytes showed gap junctional
      communication between 56.1+/-2.0% of MSCs (24 h after labeling, n=5) and neonatal
      cardiomyocytes. These findings suggest that MSCs are capable of differentiating
      into cardiomyocytes when directly cocultured with neonatal cardiomyocytes by cell
      to-cell interaction, but not with adult cardiomyocytes or conditioned medium.

PMID- 16096831
TI  - Efficacy and tolerability of darifenacin, a muscarinic M3 selective receptor
      antagonist (M3 SRA), compared with oxybutynin in the treatment of patients with
      overactive bladder.
AB  - A randomized, double-blind, placebo-controlled, four-way crossover, safety study
      of darifenacin versus oxybutynin was carried out on 76 patients with overactive
      bladder (OAB). Adults with OAB received 2 weeks each of darifenacin 15 and 30 mg
      once daily (q.d.), oxybutynin 5 mg three times daily (t.i.d.) and placebo, in
      random sequence at 10-day intervals. Darifenacin and oxybutynin significantly
      reduced incontinence episodes, and the number/severity of urgency episodes (all
      P<0.05 versus placebo). Improvements in OAB symptoms with darifenacin were dose
      dependent. Dry mouth was less common with darifenacin 15 mg than oxybutynin (13%
      and 36%; P<0.05), while constipation was comparable (10% and 8%, respectively).
      Corresponding rates for darifenacin 30 mg were 34% and 21%, respectively.
      Patients only reported blurred vision or dizziness with oxybutynin (3% and 2%,
      respectively). Darifenacin (15 mg q.d.) provides comparable efficacy with
      improved tolerability versus oxybutynin (5 mg t.i.d.) in the treatment of
      patients with OAB.

PMID- 16096832
TI  - Current usefulness of free/total PSA ratio in the diagnosis of prostate cancer at
      an early stage.
AB  - The aim of our study was to evaluate five different free/total PSA (f/t PSA) kits
      for the diagnosis of early stage prostate cancer. We compared the PSA density and
      the f/t PSA ratio to differentiate between benign prostatic hyperplasia (BPH) and
      prostate cancer. This prospective study included a total of 120 patients with
      suspected prostate cancer (PSA between 4 and 15 ng/ml) observed over a period of
      30 months. All patients had a blood test as well as a prostate biopsy prior to
      inclusion. Serum immunoassay total-PSA (t PSA) and free-PSA (f PSA) were carried
      out using five different assay kits: IMX Abbott (A), Kryptor Brahms (B), Immulite
      DPC (D), IRMA Immunotech (I) and IRMA DiaSorin (S). The results were compared to
      determine sensitivity, specificity, threshold values, and to differentiate
      between BPH and cancer. No difference was found between assay reproducibility and
      variation in the assays, however, only a slight variation was observed in the
      mean t PSA values, whereas a significant difference was found with f/t PSA.
      Receiver operating curves were generated for t-PSA and f/t PSA. The area under
      the curves did not show any significant differences for either t PSA or f/t PSA.
      A low comparative variability between the five kits tested for tPSA was observed,
      which suggest that the f/t PSA ratio has no current usefulness in the initial
      diagnosis of prostate cancer, particularly in patients with larger prostates.
      Furthermore, no prognostic value was found for surgically positive margins in
      radical prostatectomy.

PMID- 16096833
TI  - Nonlinear elastic-viscoplastic constitutive equations for aging facial tissues.
AB  - This paper reports on the initial stages of a project to simulate the nonlinear
      mechanical behavior of an aging human face. A cross-section of the facial
      structure is considered to consist of a multilayered composite of tissues with
      differing mechanical behavior. The constitutive properties of these tissues are
      incorporated into a finite element model of the three-dimensional facial
      geometry. Relatively short time (elastic-viscoplastic) behavior is governed by
      equations previously developed which are consistent with mechanical tests. The
      long time response is controlled by the aging elastic components of the tissues.
      An aging function is introduced which, in a simplified manner, captures the
      observed loss of stiffness of these aging elastic components due to the history
      of straining as well as other physiological and environmental influences.
      Calculations have been performed for 30 years of exposure to gravitational
      forces. Progressive gravimetric soft tissue descent is simulated, which is
      regarded as the main indication of facial aging. Results are presented for the
      deformations and stress distributions in the layers of the soft tissues.

PMID- 16096834
TI  - Isolation and partial characterization of a cryptic polyene gene cluster in
      Pseudonocardia autotrophica.
AB  - The polyene antibiotics, a category that includes nystatin, pimaricin,
      amphotericin, and candicidin, comprise a family of very promising antifungal
      polyketide compounds and are typically produced by soil actinomycetes. The
      biosynthetic gene clusters for these polyenes have been previously investigated,
      revealing the presence of highly similar cytochrome P450 hydroxylase (CYP) genes.
      Using polyene CYP-specific PCR screening with several actinomycete genomic DNAs,
      Pseudonocardia autotrophica was determined to contain a unique polyene-specific
      CYP gene. Genomic DNA library screening using the polyene-specific CYP gene probe
      identified a positive cosmid clone, which contained a DNA fragment of
      approximately 34.5 kb. The complete sequencing of this DNA fragment revealed a
      total of seven complete and two incomplete open reading frames, which were found
      to be highly similar, but still unique, when compared to previously known polyene
      biosynthetic genes. These results suggest that the polyene-specific screening
      approach may constitute an efficient method for the isolation of potentially
      valuable cryptic polyene biosynthetic gene clusters from various rare
      actinomycetes.

PMID- 16096835
TI  - Differential expression and extent of fungal/plant and fungal/bacterial
      chitinases of Aspergillus fumigatus.
AB  - We provide the first indication of the extent of the complex chitinolytic system
      of a filamentous fungus. Phylogenetic analysis of the 14 apparent chitinases of
      the opportunistic fungal pathogen Aspergillus fumigatus identified four and ten
      enzymes related to plant and bacterial chitinases, respectively. Further, real
      time-RT-PCR studies revealed distinct patterns of gene expression, consistent
      with morphogenetic or nutritional roles, for members of the fungal/plant or
      fungal/bacterial sub-families, respectively. Our results provide a basis for
      future studies with A. fumigatus chitinases, which may lead to the exploitation
      of these enzymes, or their regulators, in the development of novel drug
      strategies.

PMID- 16096836
TI  - Accumulation and turnover of 23S ribosomal RNA in azithromycin-inhibited
      ribonuclease mutant strains of Escherichia coli.
AB  - Ribosomal RNA is normally a stable molecule in bacterial cells with negligible
      turnover. Antibiotics which impair ribosomal subunit assembly promote the
      accumulation of subunit intermediates in cells which are then degraded by
      ribonucleases. It is predicted that cells expressing one or more mutated
      ribonucleases will degrade the antibiotic-bound particle less efficiently,
      resulting in increased sensitivity to the antibiotic. To test this, eight
      ribonuclease-deficient strains of Escherichia coli were grown in the presence or
      absence of azithromycin. Cell viability and protein synthesis rates were
      decreased in these strains compared with wild type cells. Degradation of 23S rRNA
      and recovery from azithromycin inhibition were examined by 3H-uridine labeling
      and by hybridization with a 23S rRNA specific probe. Mutants defective in
      ribonuclease II and polynucleotide phosphorylase demonstrated hypersensitivity to
      the antibiotic and showed a greater extent of 23S rRNA accumulation and a slower
      recovery rate. The results suggest that these two ribonucleases are important in
      23S rRNA turnover in antibiotic-inhibited E. coli cells.

PMID- 16096837
TI  - Sister Joseph umbilical nodule coexisting with endometriosis from endometrial
      carcinoma.
AB  - A 58-year-old woman was diagnosed with endometrial carcinoma. Total hysterectomy,
      bilateral salpingo-oophorectomy and paraaortic and a pelvic lymph node dissection
      were performed. The cytology of peritoneal fluid was negative. There was no
      peritoneal dissemination except umbilical nodule. A peritoneal 2.0x1.5 cm
      umbilical nodule was also resected. The nodule was identified as a metastasis
      from endometrial cancer with endometriosis. The pelvic lymph nodes also showed
      metastatic lesion with endometriosis. Our case showed that endometriosis
      coexisted with umbilical and pelvic lymph nodal metastatic lesions from
      endometrial cancer. This fact suggests that the mode of metastasis to the
      umbilicus via lymph flow from endometrial cancer is the same as that for
      endometriosis.

PMID- 16096838
TI  - Stress induced changes in lymphocyte subpopulations and associated cytokines
      during whole body hyperthermia of 41.8-42.2 degrees C.
AB  - Extreme acute physical stress leads to transient impairment of T-lymphocytes,
      which are essential for tumor defence and prevention of infectious diseases.
      Radiant whole body hyperthermia (WBH) at 41.8-42.2 degrees C may enhance the
      efficacy of systemic chemotherapy in patients with advanced malignancies, but is
      associated with marked physical stress. Aim of this study was to demonstrate
      stress induced short-time effects on lymphocyte subpopulations and associated
      cytokines during WBH. Total leukocyte count, white blood cell differential blood
      count, lymphocyte subpopulations (T-helper-/T4-cells, T-suppressor-/T8-cells,
      natural-killer-/NK-cells, gammadelta-T-cells) as well as plasma levels of
      Interleukin(IL)-10, IL-12 and Interferon-gamma (IFN-gamma) were measured in ten
      patients treated with WBH and additional cytostatic chemotherapy. Blood samples
      were drawn before treatment, at three temperature points during WBH, and 24 h
      after start of treatment. Results were compared with those obtained from a
      control group consisting of six patients receiving chemotherapy alone. Numbers of
      T4-cells decreased significantly during WBH, while numbers of NK-cells and
      gammadelta-T-cells increased, resulting in transient impairments of total
      lymphocyte counts and T4/T8-ratio. IL-12 plasma levels as well as IFN-gamma/IL-10
      ratio also decreased during WBH. No significant changes were found in T8-cells of
      WBH patients. Changes were reversible within 24 h and could not been found in
      control patients. Our results support the hypothesis that WBH combined with chemo
      therapy induces a strong but reversible anti-inflammatory stress response in
      cancer patients during therapy. Further studies are necessary to examine the
      pathophysiological details and to evaluate the meaning of these transient
      immunological changes for patient's outcome.

PMID- 16096839
TI  - Association between regional quadriceps oxygenation and blood oxygen saturation
      during normoxic one-legged dynamic knee extension.
AB  - It is not clear whether muscle oxygenation (O(2-NIRS)) measured by near-infrared
      spectroscopy (NIRS) correlates with femoral venous SO2 (S(fv)o2) during normoxic
      exercise. Therefore, the purpose of this study was to compare physiologically
      calibrated O(2-NIRS) with S(fv)o2 in subjects performing one-legged dynamic knee
      extension exercise (1L-KEE). Five healthy male subjects (age 25+/-2 year, height
      177.8+/-4.8 cm, body weight 67.1 +/- 5.0 kg; mean +/- SD) performed 1L-KEE at 20,
      40, and 60% of peak work rate (WR-peak) each for 4 min. S(fv)o2 was measured at
      rest and during the 3rd minute of each work rate. O(2-NIRS) was continuously
      monitored in a proximal region of the vastus lateralis (VL-p), a distal region of
      VL (VL-d), and a proximal region of the rectus femoris (RF-p). S(fv)o2 was 56.0%
      at rest and decreased to 36.6 at 20% WR-peak, 35.8 at 40% WR-peak, and 31.1 at
      60% WR-peak. There was a significant correlation between O(2-NIRS) and S(fv)o2(VL
      p: r (2) = 0.62, VL-d: r2 = 0.35, RF-p: r2 = 0.62, with a moderate variation
      among individuals at each site; residual values = 4.83 - 11.75). These data
      indicate that NIRS measurement provides a reflection of S(fv)o2 during 20-60% WR
      peak of normoxic 1L-KEE.

PMID- 16096840
TI  - Effects of exercise intensity on lymphocyte apoptosis induced by oxidative stress
      in men.
AB  - Exercise is linked with intensity-dependent immune response. Intracellular redox
      status is important in programmed cell death. This study, by closely examining 18
      sedentary men who exercised moderately and severely (ie. 60% and 80% VO2max,
      respectively) for 40 min, investigated how exercise intensities influence
      intracellular redox status and oxidative stress-induced apoptosis in lymphocyte.
      Intracellular superoxide and reduced glutathione (GSH) levels, lipid
      peroxidation, mitochondrial transmembrane potential (MTP), active caspases
      contents, phosphotidyl serine (PS) exposure, and DNA fragmentation in lymphocytes
      were determined. Moreover, sublethal oxidative stress was administered by
      treating the lymphocyte with H2O2, to closely approximate in vivo pro-oxidative
      conditions. Immediately or 24 h after severe exercise, (1) lymphocyte GSH level
      and MTP had diminished while active caspase-8, -9, and -3 contents and DNA
      fragmentation had risen; and (2) H2O2 induced- lymphocyte PS exposure and DNA
      fragmentation were enhanced. In contrast, lymphocyte MTP, caspases activation, PS
      exposure, and DNA fragmentation were unaltered immediately following moderate
      exercise, whereas GSH level rose, lipid peroxidation diminished, and H2O2 induced
      PS exposure and cell damage reduced 24 h after this exercise. These results
      suggest that heavy exercise diminishes lymphocyte GSH content and subsequently
      enhances the oxidative stress-induced apoptosis. However, moderate exercise
      attenuates lymphocyte apoptosis induced by oxidative stress, possibly by
      improving intracellular anti-oxidative capacity.

PMID- 16096841
TI  - Metabolic and phenotypic characteristics of human skeletal muscle fibers as
      predictors of glycogen utilization during electrical stimulation.
AB  - Characteristics of skeletal muscle such as fiber type composition and activities
      of key metabolic enzymes have been purported to affect glycogen utilization.
      However, the relative importance individual factors may have in predicting
      glycogen utilization of individual muscle fibers has not been addressed. Thus, we
      sought to determine the relative importance that metabolic characteristics and
      phenotypic expression of individual fibers have in predicting fiber specific
      glycogen utilization during neuromuscular electrical stimulation (NMES) exercise.
      Biopsies were taken from the m, vastus lateralis (VL) of eight recreationally
      active males before and immediately after 30 min of non-fatiguing NMES and
      analyzed for type (I, IIa and IIx), succinate dehydrogenase activity (SDH),
      glycerol-phosphate dehydrogenase activity (GPDH), quantitative-actomyosin
      adenosine triphosphatase activity (qATPase), and glycogen content. Our results
      demonstrate that a ratio of enzyme activities representing pathways for energy
      supply and energy demand (SDH: qATPase) accounted for more of the variance in
      glycogen utilization (y=0.2091 e(-0.0329x ), R2=0.622, P< or = 0.0001) than SDH
      (R2=0.321) or qATPase (R2=0.365) alone. Fiber phenotype was also a significant
      predictor of glycogen utilization, but to a lesser extent than the other
      variables studied (R2=0.201). A ratio of the activities of enzymes representing
      pathways of energy supply and energy demand, represented by SDH:qATPase, is a
      better predictor of glycogen utilization than either of its components
      independently while fiber phenotype, although a statistically significant
      predictor of glycogen utilization, may not be the most appropriate determinate of
      the functional characteristics of an individual fiber.

PMID- 16096842
TI  - Can firefighter instructors perform a simulated rescue after a live fire training
      exercise?
AB  - Two studies were undertaken to determine whether firefighter instructors are
      capable of performing a simulated rescue task after undertaking a live fire
      training exercise (LFTE) lasting approximately 40 min. In the first study, ten
      instructors performed two simulated rescue tasks in air at 19 degrees C,
      involving dragging an 81-kg dummy for 15 m along a corridor and down two flights
      of stairs. The first rescue acted as a control (Rcontrol) and was conducted when
      they were euhydrated and normothermic. The second task was undertaken 10.4 (3.3)
      min [mean (SD)] after a LFTE resulting in an average rectal temperature of 38.1
      (0.4) degrees C (Rhot). All instructors were able to successfully complete
      Rcontrol and Rhot in 90.1 (28.6) s and 78.7 (15.6) s respectively. Heart rate
      (HR) and rating of perceived exertion (RPE) were higher after the LFTE [162 (16)
      beats min(-1) versus 180 (15) beats min(-1); and 13.3 (2.4) versus 15.7 (2.1),
      respectively, P<0.001]. In the second study, six instructors (one instructor
      participated twice giving seven trials) undertook a simulated rescue task in 16
      degrees C involving dragging an 85-kg dummy along a flat surface 79 (65) s after
      a LFTE that increased rectal temperature to 38.3 (0.7) degrees C. On six
      occasions the instructor was able to successfully complete the full 30-m drag in
      41.7 (6.9) s and one instructor dragged the dummy for 20 m before stopping
      through exhaustion. HR during the rescue task reached 173 (19) beats min(-1) and
      RPE was 16.3 (2.4). In conclusion, most of the instructors were able to perform a
      rescue task after the LFTE, however they were close to their physical limit.

PMID- 16096843
TI  - Relationship between perceived exertion and mean power frequency of the EMG
      signal from the upper trapezius muscle during isometric shoulder elevation.
AB  - The aim of the study was to investigate the relationship between a fatigue
      induced increase of perceived exertion in the neck with a decrease of mean power
      frequency (MPF) in the surface electromyography (sEMG) signal during repeated
      shoulder elevation endurance tasks. About Thirty-two healthy women (age range 20
      62) performed two maximum 6-min shoulder elevation endurance tasks at 30% of
      their maximal voluntary contraction (MVC) level, separated by a rest of 6 min.
      During these exercises, perceived exertion was estimated using the Borg scale
      (range 0-10), whereas the MPF of the sEMG signal from the upper trapezius was
      simultaneously detected. Linear regression analysis was applied over time for
      each trial and subject for both MPF and Borg scale rating values. The MPF was
      normalized by the intercept of the linear regression analysis. The resulting
      slopes of normalized mean power frequency (nMPF) and Borg scale rating were
      correlated with each other by linear regression for both trials. In order to
      investigate the individual behavior of fatigue effects between trials, Delta
      (trial 2-trial 1) slopes of nMPF and Borg scale ratings were calculated for each
      subject. These slopes of nMPF and Borg scale ratings were correlated with each
      other as well by linear regression. The increase of Borg scale ratings, as well
      as the decrease of nMPF, were significantly higher in trial 2 than trial 1
      (P<0.01). The results show a linear correlation between slopes of nMPF and Borg
      scale ratings for both trials 1 and 2 (r=0.76, P<0.01). Trial-to-trial slopes
      (Delta (trial 2-trial 1)) of nMPF and Borg scale rating, were also significantly
      correlated (r=0.68, P<0.05). Thus, the individually sensed increase of perceived
      exertion in the neck during trial 2 was accompanied by a simultaneously higher
      detected decrease of nMPF. These findings indicate a close relationship between
      subjective perception of exertion in the neck and objectively assessed muscle
      fatigue of the upper trapezius.

PMID- 16096845
TI  - Do distances among host patches and host density affect the distribution of a
      specialist parasitoid?
AB  - The effect of spatial habitat structure and patchiness may differ among species
      within a multi-trophic system. Theoretical models predict that species at higher
      trophic levels are more negatively affected by fragmentation than are their hosts
      or preys. The absence or presence of the higher trophic level, in turn, can
      affect the population dynamics of lower levels and even the stability of the
      trophic system as a whole. The present study examines different effects of
      spatial habitat structure with two field experiments, using as model system the
      parasitoid Cotesia popularis which is a specialist larval parasitoid of the
      herbivore Tyria jacobaeae. One experiment examines the colonisation rate of the
      parasitoid and the percentage parasitism at distances occurring on a natural
      scale; the other experiment examines the dispersal rate and the percentage
      parasitism in relation to the density of the herbivore and its host plant. C.
      popularis was able to reach artificial host populations at distances up to the
      largest distance created (at least 80 m from the nearest source population).
      Also, the percentage parasitism did not differ among the distances. The density
      experiment showed that the total number of herbivores parasitised was higher in
      patches with a high density of hosts, regardless of the density of the host
      plant. The percentage parasitism, however, was not related to the density of the
      host. The density of the host plant did have a (marginally) significant effect on
      the percentage parasitism, probably indicating that the parasitoid uses the host
      plant of the herbivore as a cue to find the herbivore itself. In conclusion, the
      parasitoid was not affected by the spatial habitat structure on spatial scales
      that are typical of local patches.

PMID- 16096844
TI  - Haemolysis caused by alterations of alpha- and beta-spectrin after 10 to 35 min
      of severe exercise.
AB  - The pathophysiology of exercise related haemolysis is not thoroughly understood.
      We investigated whether exercise related haemolysis (1) is associated with
      alterations of red blood cell (RBC) membrane proteins similar to those found in
      inherited anaemic diseases, (2) can be induced with a non-running exercise mode,
      (3) is related to exercise intensity, and (4) coincides with indicators of
      oxidative stress. In ten triathletes [median (P25/P75-percentiles) age: 28.0
      (26.3/28.5) years, height: 1.84 (1.78/1.87) m, body mass: 78.5 (74.8/80.8) kg,
      maximal oxygen uptake: 60.0 (57.3/64.8) ml kg(-1) min(-1)], haptoglobin, alpha-
      and beta-spectrin bands, malondialdehyde (MDA) and H2O2-induced chemiluminescence
      (H2O2-Chem) were determined immediately pre- and post-both, a 35 min low
      intensity and a high intensity cycling exercise [240 (218/253) vs 290 (270/300)
      W, P<0.05) requiring similar amounts of metabolic energy [28.3 (25.9/29.9) vs
      24.9 (18.4/30.5) kJ kg(-1), P>0.05]. At high exercise intensity haptoglobin [1.10
      (0.81/2.53) vs 1.01 (0.75/2.00) g l(-1)] decreased (P<0.05) whilst MDA [2.80
      (2.65/3.20) vs 3.13 (2.78/3.31) nmol ml(-1)] and H2O2-Chem [29.70 (22.55/37.10)
      vs 37.25 (35.20/52.63) rel. U min] increased (P<0.05), coinciding with the
      disappearance of the spectrin bands in six out of ten gels. No corresponding
      changes were found at low intensity exercise. Ten to 35 min of non-running
      exercise in a regularly used intensity domain causes intra-vascular haemolysis
      associated with alterations in the RBC membrane proteins similar to those found
      after in vitro oxidative stress and in inherited anaemic diseases like
      Sphaerocytosis and Fanconi's anaemia.

PMID- 16096846
TI  - Riparian plant species loss alters trophic dynamics in detritus-based stream
      ecosystems.
AB  - Riparian vegetation is closely connected to stream food webs through input of
      leaf detritus as a primary energy supply, and therefore, any alteration of plant
      diversity may influence aquatic ecosystem functioning. We measured leaf litter
      breakdown rate and associated biological parameters in mesh bags in eight
      headwater streams bordered either with mixed deciduous forest or with beech
      forest. The variety of leaf litter types in mixed forest results in higher food
      quality for large-particle invertebrate detritivores ('shredders') than in beech
      forest, which is dominated by a single leaf species of low quality. Breakdown
      rate of low quality (oak) leaf litter in coarse mesh bags was lower in beech
      forest streams than in mixed forest streams, a consequence of lower shredder
      biomass. In contrast, high quality (alder) leaf litter broke down at similar
      rates in both stream categories as a result of similar shredder biomass in coarse
      mesh bags. Microbial breakdown rate of oak and alder leaves, determined in fine
      mesh bags, did not differ between the stream categories. We found however aquatic
      hyphomycete species richness on leaf litter to positively co-vary with riparian
      plant species richness. Fungal species richness may enhance leaf litter breakdown
      rate through positive effects on resource quality for shredders. A feeding
      experiment established a positive relationship between fungal species richness
      per se and leaf litter consumption rate by an amphipod shredder (Gammarus
      fossarum). Our results show therefore that plant species richness may indirectly
      govern ecosystem functioning through complex trophic interactions. Integrating
      microbial diversity and trophic dynamics would considerably improve the
      prediction of the consequences of species loss.

PMID- 16096847
TI  - Foliar and fungal 15N:14N ratios reflect development of mycorrhizae and nitrogen
      supply during primary succession: testing analytical models.
AB  - Nitrogen isotopes (15N/14N ratios, expressed as delta15N values) are useful
      markers of the mycorrhizal role in plant nitrogen supply because discrimination
      against 15N during creation of transfer compounds within mycorrhizal fungi
      decreases the 15N/14N in plants (low delta15N) and increases the 15N/14N of the
      fungi (high delta15N). Analytical models of 15N distribution would be helpful in
      interpreting delta15N patterns in fungi and plants. To compare different
      analytical models, we measured nitrogen isotope patterns in soils, saprotrophic
      fungi, ectomycorrhizal fungi, and plants with different mycorrhizal habits on a
      glacier foreland exposed during the last 100 years of glacial retreat and on
      adjacent non-glaciated terrain. Since plants during early primary succession may
      have only limited access to propagules of mycorrhizal fungi, we hypothesized that
      mycorrhizal plants would initially be similar to nonmycorrhizal plants in
      delta15N and then decrease, if mycorrhizal colonization were an important factor
      influencing plant delta15N. As hypothesized, plants with different mycorrhizal
      habits initially showed similar delta15N values (-4 to -6 per thousand relative
      to the standard of atmospheric N2 at 0 per thousand), corresponding to low
      mycorrhizal colonization in all plant species and an absence of ectomycorrhizal
      sporocarps. In later successional stages where ectomycorrhizal sporocarps were
      present, most ectomycorrhizal and ericoid mycorrhizal plants declined by 5-6 per
      thousand in delta15N, suggesting transfer of 15N-depleted N from fungi to plants.
      The values recorded (-8 to -11 per thousand) are among the lowest yet observed in
      vascular plants. In contrast, the delta15N of nonmycorrhizal plants and
      arbuscular mycorrhizal plants declined only slightly or not at all. On the
      forefront, most ectomycorrhizal and saprotrophic fungi were similar in delta15N (
      1 to -3 per thousand), but the host-specific ectomycorrhizal fungus Cortinarius
      tenebricus had values of up to 7 per thousand. Plants, fungi and soil were at
      least 4 per thousand higher in delta15N from the mature site than in recently
      exposed sites. On both the forefront and the mature site, host-specific
      ectomycorrhizal fungi had higher delta15N values than ectomycorrhizal fungi with
      a broad host range. From these isotopic patterns, we conclude: (1) large
      enrichments in 15N of many ectomycorrhizal fungi relative to co-occurring
      ectomycorrhizal plants are best explained by treating the plant-fungal-soil
      system as a closed system with a discrimination against 15N of 8-10 per thousand
      during transfer from fungi to plants, (2) based on models of 15N mass balance,
      ericoid and ectomycorrhizal fungi retain up to two-thirds of the N in the plant
      mycorrhizal system under the N-limited conditions at forefront sites, (3)
      sporocarps are probably enriched in 15N by an additional 3 per thousand relative
      to available nitrogen, and (4) host-specific ectomycorrhizal fungi may transfer
      more N to plant hosts than non-host-specific ectomycorrhizal fungi. Our study
      confirms that nitrogen isotopes are a powerful tool for probing nitrogen dynamics
      between mycorrhizal fungi and associated plants.

PMID- 16096848
TI  - Testing the optimal defense theory and the growth-differentiation balance
      hypothesis in Arabidopsis thaliana.
AB  - Two prominent theories proposed to explain patterns of chemical defense
      expression in plants are the optimal defense theory (ODT) and the growth
      differentiation balance hypothesis (GDBH). The ODT predicts that plant parts with
      high fitness value will be highly defended, and the GDBH predicts that slow
      growing plant parts will have more resources available for defense and thus will
      have higher defense levels than faster growing tissues. We examined growth rate,
      fitness value, and defense protein levels in leaves of a wild and lab ecotype of
      Arabidopsis thaliana to address whether patterns of defense protein expression in
      this plant conform to predictions of either the ODT or the GDBH. We divided
      leaves of A. thaliana into six leaf classes based on three developmental stages:
      vegetative, bolting, and flowering; with two leaf ages at each stage: young and
      old. We assessed the fitness value of leaves by determining the impact of the
      removal of each leaf class on total seed production and germination rates.
      Although A. thaliana was highly tolerant to defoliation, young leaves were more
      valuable than old in general, and young leaves on bolting plants were the most
      valuable leaf class in particular. Young leaves on vegetative plants grew fastest
      in both ecotypes, while old leaves on bolting and flowering plants grew slowest.
      Finally, defense levels were assessed in each leaf class by quantifying the
      constitutive and inducible expression of four defense-related proteins.
      Expression of guaiacol peroxidase and chitinase activity conformed largely to
      GDBH predictions. Expression of trypsin inhibitor and polyphenoloxidase activity
      varied by leaf class and treatment, but conformed to neither GDBH nor ODT
      predictions.

PMID- 16096849
TI  - Variable effects of climate change on six species of North American birds.
AB  - Many recent studies have shown that birds are advancing their laying date in
      response to long-term increases in spring temperatures. These studies have been
      conducted primarily in Europe and at local scales. If climate change is a large
      scale phenomenon, then we should see responses at larger scales and in other
      regions. We examined the effects of long-term temperature change on the laying
      dates and clutch sizes of six ecologically diverse species of North American
      birds using 50 years of nest record data. As predicted, laying dates for most
      (four of six) species were earlier when spring temperatures were warmer. Over the
      long-term, laying dates advanced over time for two species (red-winged
      blackbirds, Agelaius phoeniceus and eastern bluebirds, Sialia sialis). Laying
      date of song sparrows (Melospiza melodia) also advanced with increasing
      temperature when the analysis was restricted to eastern populations. Neither
      laying date nor clutch sizes changed significantly over time in the remaining
      species (American coot, Fulica americana, killdeer, Charadrius vociferous, and
      American robin, Turdus migratorius), an unsurprising result given the lack of
      increase in temperatures over time at nest locations of these species. This study
      indicates that the relationship between climate change and breeding in birds is
      variable within and among species. In large-scale analyses of North American
      birds, four of seven species have shown advances in laying dates with increasing
      temperature (including song sparrows in the east). These variable responses
      within and among species highlight the need for more detailed studies across
      large spatial scales.

PMID- 16096853
TI  - Antibodies against protein Z and fetal loss: current perspectives.
AB  - Protein Z (PZ) is a vitamin K-dependent plasma protein that serves as a cofactor
      for the inactivation of factor Xa. A number of investigators found low PZ levels
      in patients with haemorrhagic as well as thromboembolic diseases, although there
      is no clear evidence of a pathogenic link between PZ deficiency and these
      clinical disorders. Nevertheless, low PZ levels have been found in association
      with early fetal losses, especially those occurring before the 15th week of
      gestation and in patients with detectable antiphospholipid and anti-PZ
      antibodies. The current diagnostic relevance and therapeutic consequences of
      these parameters will be discussed.

PMID- 16096852
TI  - Human basophils as effectors and immunomodulators of allergic inflammation and
      innate immunity.
AB  - Basophils have often stood in the shadow of their tissue-fixed mast cell
      counterparts which share some, common features, such as high-affinity IgE
      receptor expression and the ability to release histamine. That rodent mast cells
      produce a variety of pro-allergic and inflammatory cytokines has further added to
      the deception that basophils only play a minor role in allergic inflammation.
      Surprisingly, in humans, basophils, but not mast cells, appear to be the prime
      early producers of the Th2-type cytokines IL-4 and IL-13, which perform several
      crucial functions in initiating and maintaining allergic responses. This putative
      immunomodulatory role of basophils is supported further by their ability to
      express CD40 ligand, which, together with IL-4 and IL-13, serve as inductors of B
      cell proliferation and class switching to IgE and IgG4. Moreover, human basophils
      are the main cellular source for rapid IL-4 generation, a mandatory requirement
      for the development of Th2 responses. Recent specific staining techniques have
      localised basophils in various tissues affected by allergic diseases and it
      appears likely, but remains to be proven, that the interaction of basophils, T
      cells and B cells at these sites propagate pro-allergic immune responses.
      Additionally, basophil activation is not restricted to antigen-specific IgE
      crosslinking but can be caused in non-sensitised individuals by parasitic
      antigens, plant lectins and viral superantigens binding to non-specific IgEs.
      Finally, the presence of novel IgE-independent receptor targets that cause
      trafficking and Th2 cytokine release from basophils further underlines their
      potential role in innate as well as adaptive immunity.

PMID- 16096850
TI  - Effects of irradiation and cisplatin on human glioma spheroids: inhibition of
      cell proliferation and cell migration.
AB  - PURPOSE: Investigation of cell migration and proliferation of human glioma cell
      line spheroids (CLS) and evaluation of morphology, apoptosis, and
      immunohistochemical expression of MIB-1, p53, and p21 of organotypic muticellular
      spheroids (OMS) following cisplatin (CDDP) and irradiation (RT). MATERIAL AND
      METHODS: Spheroids of the GaMg glioma cell line and OMS prepared from biopsy
      tissue of six glioblastoma patients were used. Radiochemosensitvity (5 microg/ml
      CDDP followed by RT) was determined using migration and proliferation assays on
      CLS. In OMS, histology and immunohistochemical studies of MIB-1, p53, and p21
      expression were examined 24 and 48 h following treatment. RESULTS: Combination
      treatment led to a migration inhibition of 38% (CDDP 13%; RT 27%) and specific
      growth delay of 2.6 (CDDP 1.3; RT 2.1) in CLS. Cell cycle analysis after
      combination treatment showed an accumulation of cells in the G2/M phase. In OMS,
      apoptosis increased, cell proliferation decreased, and p53/p21 expression
      increased more pronounced following CDDP+RT. No morphological damage was
      observed. CONCLUSION: CDDP can lead to enhancement of the RT effect in spheroids
      of both human glioma cell line spheroids and biopsy spheroids from glioblastoma
      specimens. The exerted effect is additive rather than synergistic.

PMID- 16096854
TI  - Conventional and molecular cytogenetic findings of myelodysplastic syndrome
      patients.
AB  - Myelodysplastic syndrome (MDS) involves myeloid cells of the bone marrow, which
      is important in progressive bone marrow insufficiency. Of all MDS patients, 40%
      50% have at least one chromosomal rearrangement. Loss of specific chromosomal
      regions like 5q- and 7q- are usually the secondary cytogenetic abnormalities
      associated with MDS. In order to detect chromosome abnormalities associated with
      MDS, bone marrow samples from 26 patients diagnosed as MDS were obtained prior to
      chemotherapy. Both conventional cytogenetic analyses and fluorescence in situ
      hybridisation (FISH) methods were performed and locus-specific probes for 5q and
      7q were used. Results obtained were compared. Twenty-one patients had normal
      karyotypes and four patients had abnormal karyotypes, while in one patient we
      could not obtain metaphases from cultures. Three patients with normal karyotypes
      revealed del (5q), two patients had del (7q) and one patient had monosomy (7). A
      total of 10 of 26 patients had chromosome changes visualised by either
      conventional or molecular cytogenetics (approximately 38.5%). Our results show
      that both methods are important in diagnosis and follow up of MDS patients. When
      used together, conventional cytogenetics and FISH detect clinically significant
      chromosome abnormalities in MDS patients.

PMID- 16096855
TI  - Serum adenosine deaminase and procalcitonin concentrations in neutropenic febrile
      children with acute lymphoblastic leukaemia.
AB  - Neutropenia as a state of immunosuppression is probably the major problem in
      patients suffering from acute lymphoblastic leukaemia undergoing intensive
      chemotherapy. Fever is frequent in neutropenic patients and often related to
      infection. Clinically, the presence of infection in patients with neutropenia may
      be difficult to establish, because there are usually few signs of infection. The
      aim of this work was to study sensitive markers for early diagnosis of microbial
      infection in neutropenic children undergoing intensive chemotherapy as a
      treatment for acute lymphoblastic leukaemia. The study included three groups (A,
      B and C) of children with acute lymphoblastic leukaemia and neutropenia. Group A
      consisted of 29 children with febrile neutropenia and microbial infection, aged 1
      14 years (5.8+/-2.9), 11 boys and 18 girls; Group B of 38 children with febrile
      neutropenia without microbial infection, aged 2-14 years (6.8+/-3.1), 14 boys and
      24 girls; and Group C of 53 children with neutropenia without fever and without
      infection, aged 1-14 years (5.9+/-2.1), 21 boys and 32 girls. Blood samples were
      collected upon admission and before the start of any antimicrobial treatment. The
      samples were used for blood culture, serological tests, leukocyte count and
      analysis of levels of C-reactive protein, procalcitonin, total adenosine
      deaminase (ADA) activity and its isoenzymes, ADA-1 and ADA-2. According to our
      results the procalcitonin levels and total ADA activity discriminated best
      between neutropenic febrile (Groups A and B) and neutropenic afebrile episodes
      (Group C). In conclusion, this study suggests procalcitonin and total ADA
      activity as two easily measurable and cost effective markers for the assessment
      of immune response in febrile neutropenic patients with acute lymphoblastic
      leukaemia.

PMID- 16096856
TI  - The effects of taking chronic nitrate by drinking water on thyroid functions and
      morphology.
AB  - Nitrate incorporation in humans takes place via drinking water and food. The
      water used for drinking and cooking in the goitrous areas is high in nitrate
      content. The aim of the present study was to evaluate both chronic effects and
      the dose-response relationship of nitrate on thyroid functions. A total of rats
      were divided into 5 work groups and sodium nitrate was added to their drinking
      water in different concentrations (0, 50, 100, 250 and 500 mg/l) over a 30-week
      period. The radioiodine uptake of thyroid was decreased in the 50 mg/l nitrate
      group, whereas it was increased in the 250 and 500 mg/l nitrate groups as
      compared to control. All hormones of thyroid gland except total thyroxine and
      thyroid-stimulating hormone were decreased in the 50, 250 and 500 mg/l nitrate
      groups. However, the level of total thyroxin was increased in the 100 mg/l
      nitrate group. Thyroid gland weights were increased in all experimental groups.
      Histomorphological changes were observed in the 250 and 500 mg/l nitrate groups.
      These findings suggest that nitrate impairs thyroid function involving the
      hypothalamo-hypophysio-thyroid axis. This observation could contribute to the
      current discussion about the acceptable daily intake of nitrate, as well as
      drinking water nitrate standard safety margins.

PMID- 16096857
TI  - HLA DR/DQ alleles and risk of type I diabetes in childhood: a population-based
      case-control study.
AB  - The objective was to evaluate HLA DR/DQ alleles and their risk factor for type 1
      diabetes in the Abruzzo region (central Italy). Sixty incident cases from the
      Abruzzo region were studied together with 120 unrelated control subjects living
      in the same administrative areas. The relative risk of diabetes associated with
      the alleles under study was calculated by deriving the odds ratio (OR) maximum
      likelihood estimates and their 95% confidence intervals (CI) by the
      exponentiation of the logistic regression beta-parameter. The combination
      DRB1*03/DQA1*0501/DQB1*0201 was found in 20.0% of patients and 7.1% of the
      control subjects, conferring an OR of 4.04 and a CI of 1.97-8.49. The combination
      DRB1*04/DQA1*0301/DQB1*0302 was found in 23.3% of diabetic patients and 6.7% of
      controls, giving an OR of 5.69 and a CI of 2.77-12.05.
      DRB1*11/DQA1*0505/DQB1*0301 and DQA1*0505/DQB1*0301 were negatively associated
      with type 1 diabetes (OR=0.27, CI 0.11-0.57; OR=0.07, CI 0.02-0.19). The DQA1
      genotype at risk was found to be DQA1*0301/DQA1*0501: OR=23.80, CI 2.97-190.89,
      as it occurred with the highest frequency in the patient group. The DQB1 genotype
      at risk was found to be DQB1*0201/DQB1*0302, which occurred in 13.3% of patients
      but in only 1.1% of the control group (OR=29.75, CI 5.36-549.25). Our results
      shed further light on the risk of development of this disease during a specific
      time period in an area where the overall incidence of type 1 diabetes is known.

PMID- 16096858
TI  - Autoantibodies against bactericidal/permeability-increasing protein (BPI-ANCA) in
      cystic fibrosis patients treated with azithromycin.
AB  - Autoantibodies against bactericidal/permeability-increasing protein (BPI-ANCA)
      were found in patients with cystic fibrosis (CF). It is speculated that they
      represent a marker of the chronic endobronchial infection and sustained
      inflammatory response in CF. Our aim was to evaluate whether azithromycin (AZM),
      through its antiinflammatory effect, could affect the level of BPI-ANCA in CF
      patients. Eighteen patients with CF aged 5.5-36.3 years (median 15.1) were
      enrolled in a randomised, double-blind, placebo-controlled trial of AZM (250 mg
      twice a week to 10 patients) or placebo (8 patients) for 12 weeks. BPI-ANCA
      levels were recorded pre- and post-treatment and compared to a group of 18
      matched healthy controls. Chi-square analysis, Kruskal-Wallis and Mann-Whitney
      tests were used to compare between the groups. Pre- and post-treatment values
      were compared using the Wilcoxon Signed-Ranked test. BPI-ANCA was found in 12 CF
      patients (67%) and four (22%) healthy subjects (P<0.001). The mean BPI-ANCA level
      was 3.94+/-6.15 U/ml (mean+/-SD) in healthy subjects and 38.11+/-42.34 U/ml in CF
      patients (P=0.023). The mean BPI-ANCA level was higher in patients with
      Pseudomonas aeruginosa compared to those without (64+/-35 U/ml and 25+/-41 U/ml
      respectively, P=0.032). No change in BPI-ANCA levels occurred in the AZM-treated
      patients [35 (0-127) U/ml (median (range) and 30 (0-120) U/ml, respectively] or
      in the placebo group [10 (0-66) U/ml and 13 (0-83) U/ml, respectively]. BPI-ANCA
      levels are significantly higher in patients with CF compared to healthy controls.
      BPIANCA levels are higher among patients colonised with P. aeruginosa. Twelve
      weeks of AZM therapy did not lower the BPI-ANCA level in patients with CF.

PMID- 16096859
TI  - Integrating multiple clinical information systems using the Java message service
      framework to enable the delivery of urgent exam results at the point of care.
AB  - The aim of this study is to determine if network-enabled personal digital
      assistants (PDAs) can be used to facilitate the timely delivery of urgent
      radiological exam results by reducing the interval from when the radiologist's
      initial interpretation is available to when it is first viewed by an emergency
      department (ED) physician. A web- and Java message service (JMS)-based
      application was built to replace the original fax-based wet-read procedure. The
      new system allows radiologists to enter wet-reads from the picture archiving and
      communication system (PACS) display station and to track discrepancies between
      the wet-read and final report. It also notifies the ED physicians when exam
      results are available via the PDAs and permits them to view the full text of the
      wet-read and final reports from the devices. The new system is compared to the
      original procedure with the results showing improvements with the wireless
      method. Furthermore, feedback from a qualitative survey of PDA users was
      positive, suggesting that PDAs may provide one means for accessing urgent
      clinical data at the point of care.

PMID- 16096860
TI  - Effect of superficial venous surgery on venous function in chronic venous
      insufficiency.
AB  - Patients with chronic venous insufficiency often have combined superficial and
      deep venous incompetence. The aims of this study were to determine the effects of
      superficial venous surgery (SVS) on deep venous haemodynamics and on ambulatory
      venous pressure (AVP) and to determine if the AVP tourniquet test can predict the
      effect of SVS. Of 119 legs, 42 legs (32 subjects) with chronic venous
      insufficiency, healed ulceration, or active ulceration and with combined
      superficial and deep incompetence underwent preoperative duplex imaging and AVP
      measurement followed by appropriate SVS. Four months later, all underwent
      postoperative duplex imaging and AVP measurement. The pressure relief index (PRI)
      was calculated from the AVP measurement as an overall assessment of venous
      function. Seventeen of 119 (14%) showed no tourniquet improvement in PRI and were
      therefore excluded from SVS. Of those suitable for SVS, median (range) age was 56
      (32-78) years. Twenty-two limbs underwent long saphenous surgery, four limbs
      short saphenous surgery, and 16 limbs both, based on duplex findings. Segmental
      deep incompetence resolved in 11/21 (52%) limbs after surgery compared to 6/21
      (29%) with multisegment incompetence. Median (range) PRI improved from 319 (4
      1,600) preoperatively to 1,300 (360-2,670) postoperatively (p < 0.001, Wilcoxon).
      PRI with thigh tourniquet correlated with postoperative PRI (r = +0.828, p =
      0.01, Spearman), as did calf tourniquet (r = +0.996, p = 0.004) and both
      tourniquets (r = 0.535, p = 0.046). The majority of patients with combined
      superficial and deep incompetence can be selected for SVS on the basis of AVP
      measurement with tourniquets. SVS can improve segmental deep incompetence and PRI
      in those properly selected.

PMID- 16096861
TI  - Management of brachial artery pseudoaneurysms secondary to drug abuse.
AB  - Arterial pseudoaneurysm secondary to parenteral drug abuse poses a difficult
      problem to vascular surgeons. This study prospectively evaluates the outcome of
      surgical treatment for brachial artery pseudoaneurysms secondary to drug abuse.
      From February 1996 to July 2003, all brachial artery pseudoaneurysms secondary to
      drug abuse as diagnosed by duplex imaging were recruited for the study. Aneurysm
      excision, ligation, and radical debridement along with revascularization by axial
      reanastomosis were performed for all patients except one with chronic
      degenerative fusiform aneurysm, who received aneurysm resection and interposition
      reverse saphenous vein graft. Upper limb arterial flow was evaluated clinically
      and with hand-held Doppler in the perioperative period and during subsequent
      follow-up. During the study period, nine consecutive patients presented with
      cubital fossa swelling following deliberate drug arterial injections. Two of them
      suffered from thromboembolic complications and were managed conservatively by
      heparinization. Seven patients (six male, one female), aged 32-53, were confirmed
      to have brachial artery pseudoaneurysms by duplex scan and recruited for data
      analysis. Pseudoaneurysms ranged 10-40 mm in size. One ex-heroin abuser, who
      presented with median nerve palsy, underwent aneurysm resection and reversed
      saphenous vein interposition. The other six patients presented with painful
      pulsatile cubital fossa swellings. They underwent aneurysm resection, extensive
      debridement, and primary axial reanastomosis. There were no perioperative
      procedure-related complications. With an average follow-up of 38.7 months, no
      recurrences or neurovascular complications were detected. Routine
      revascularization by aneurysm resection and axial anastomosis for brachial artery
      pseudoaneurysm secondary to drug abuse is a safe, effective approach with low
      associated morbidity.

PMID- 16096862
TI  - Disease progression in the contralateral carotid artery after endarterectomy.
AB  - Our objectives were to establish the incidence and progression of stenotic
      lesions in the contralateral carotid artery (CCA) after endarterectomy, to
      identify subpopulations of patients at risk of contralateral disease progression,
      and to evaluate the efficacy of duplex scanning surveillance at detecting these
      lesions. We performed a prospective study on 180 patients in whom the CCA to the
      operated artery was healthy or showed <70% stenosis. All patients had completed a
      clinical and hemodynamic follow-up program, including duplex scanning of both
      carotids, with sessions 3 and 6 months after surgery and then every semester
      until 2 years. Thereafter, examinations were scheduled according to the severity
      of stenosis. Mean follow-up time was 26.2 months (range 1.6-67.6). Disease
      progression was observed in 26 lesions (15%), nine of which (5.5%) progressed to
      severe stenosis (SS). Kaplan-Meier event-free rates of any disease progression
      were 89%, 88%, 82%, and 79% for 1, 2, 3, and 4 years, respectively. Event-free
      rates of progression to SS were 98%, 96%, 93%, and 90.6%, respectively, for 1, 2,
      3, and 4 years. The risk of progression to SS was five times higher for stenoses
      that were moderate at the start of the study (p = 0.025). Severe contralateral
      stenoses were more common and appeared later during follow-up than ipsilateral
      restenoses. Progression of contralateral stenotic lesions is not uncommon and is
      essentially related to the presence of a moderate lesion at the start of follow
      up. Indeed, moderate stenosis is a risk factor for progression to SS, which
      appears later and more frequently than ipsilateral restenosis. It therefore seems
      that patients with a moderate contralateral lesion would benefit from long-term
      duplex ultrasound surveillance.

PMID- 16096864
TI  - Umbilical pilonidal sinus disease: predisposing factors and treatment.
AB  - Pilonidal sinus disease is a common problem of sacrococcygeal region. However, it
      is also observed in the periumbilical area. There are only a few reports about
      umbilical pilonidal sinus in the literature. In this study, 26 patients (24 men
      (92 %), 2 women (8 %) with a mean age of 22 years) with umbilical pilonidal sinus
      disease were included. Predisposing factors, patient characteristics, treatment
      modalities, and their results have been studied. Male sex, young age, hairiness,
      deep navel, and poor personal hygiene were found to be predisposing factors.
      Twenty-five patients were treated conservatively. However, two patients failed to
      respond to conservative treatment. Those patients underwent surgery where
      umbilectomy was carried out without reconstruction. One patient was also operated
      on for the preoperative misdiagnosis of irreducible umbilical hernia. Patients
      were followed for 14-96 months. We recommend conservative treatment in patients
      with umbilical pilonidal sinus. Surgery should be performed in recurrent cases
      resistant to conservative treatment. The importance of differential diagnosis of
      umbilical pilonidal sinus from other umbilical pathologies is also emphasized.

PMID- 16096863
TI  - Relevance of electronic health information to doctors in the developing world:
      results of the Ptolemy Project's Internet-based Health Information Study (IBHIS).
AB  - The aim of this study was to determine the current usage, relevance, and
      preferences for electronic health information (EHI) in the participant surgeons'
      clinical, research, and teaching activities. The Internet-Based Health
      Information Survey (IBHIS) was conducted from August to December 2003. Thirty
      seven doctors (primarily practicing in East Africa) participated, all of whom had
      been using the Ptolemy resources for at least 6 months. Survey questions
      concerned time spent reading medical literature, preferred information sources,
      preferred type of publication, relevance, preference for western versus local
      medical literature, and academic productivity. Among the 75 eligible
      participants, 37 (48%) responded. From these responses it was found that African
      surgeons with access to EHI read more than articles than they did before they had
      such access, and they find that the information obtained is highly relevant to
      their clinical, teaching, and research activities. They prefer electronic
      journals to textbooks and are more inclined to change their practice based on
      information found in western journals than local journals. Ptolemy resources
      helped the respondents who reported academic work write a total of 33 papers for
      presentation or publication. Overall, access to EHI enables doctors in Africa to
      read more, is relevant, and contributes directly to academic productivity; thus
      Western medical literature is useful in the developing world, and EHI delivery
      should continue to expand.

PMID- 16096865
TI  - Gastric cancer precursor lesions and Helicobacter pylori infection in patients
      with partial gastrectomy for peptic ulcer.
AB  - The mucosa of the gastric stump is considered at greater risk of dysplastic and
      neoplastic changes than that of the intact stomach. The combination of enteric
      reflux and Helicobacter pylori infection may have a synergistic damaging effect
      on the mucosa of the gastric remnant, both producing and increasing mucosal
      proliferation. The aim of this study was to assess whether the occurrence of H.
      pylori infection in the remnant mucosa of partially gastrectomized subjects for
      peptic ulcer disease is associated with an increase of the mucosal precursor
      lesions of malignancy. A series of 151 subjects who underwent partial gastrectomy
      for peptic ulcer disease were submitted to upper digestive endoscopy for long
      term surveillance. Biopsy specimens of the gastric stump were tested for the
      occurrence of H. pylori infection and for the presence of precancerous mucosal
      lesions. The prevalence of H. pylori colonization in the remnant stomach was less
      than 30% and similar in subjects with different time intervals between
      gastrectomy and endoscopy. Age at surgery (chi(2): p = 0.03) and H. pylori
      infection (chi(2): p = 0.002) were significantly associated with the grading of
      mucosal lesions. The prevalence of normal mucosa was 10 times higher in H. pylori
      negative patients as in H. pylori-positive ones (22.0% vs. 2.4%), and the
      prevalence of intestinal metaplasia was four times higher in H. pylori-positive
      patients than in H. pylori-negative ones (19.6% vs. 4.6%). We concluded that H.
      pylori infection may play a causal role in the development of gastric lesions in
      the operated stomach.

PMID- 16096866
TI  - Extracolonic findings at CT colonography.
AB  - This review focuses on the detection of extracolonic findings at CT colonography
      (CTC). Since its introduction, it has been regarded as a promising alternative to
      conventional colonoscopy for the detection of colorectal polyps and cancers.
      Unlike conventional colonoscopy and barium enema, CTC allows evaluation not only
      of the colon but also visualization of the lung bases, the abdomen, and the
      pelvis. CTC is performed with thin sections (1-5 mm) and small intervals (0.5-2
      mm), enabling superb image reconstruction. The ability to evaluate the
      extracolonic structures can present a clinical dilemma. On the one hand, CTC may
      incidentally demonstrate asymptomatic malignant diseases or other clinically
      important conditions, thus possibly reducing morbidity or mortality. On the other
      hand, CTC may reveal numerous findings of no clinical relevance; this could
      result in costly additional diagnostic examinations with an increase in morbidity
      and overall negative impact on patients' health. In this article, extracolonic
      findings at CTC will be reviewed and the potential benefits and disadvantages
      will be presented.

PMID- 16096867
TI  - Mesenteric desmoid mimicking recurrent testicular cancer.
AB  - The detection of a solid abdominal mass after surgery for testicular cancer most
      frequently represents metastatic disease. We report an unusual case of mesenteric
      desmoid tumor presenting after retroperitoneal lymph node dissection for
      metastatic testicular cancer. To our knowledge, there are no similar reports in
      the radiology literature.

PMID- 16096868
TI  - Splenic hypoperfusion as a sign of systemic amyloidosis.
AB  - BACKGROUND: The spleen is frequently involved in systemic amyloidosis; however,
      the computed tomographic (CT) or magnetic resonance (MR) pattern of splenic
      amyloidosis is not sufficiently described in the literature. This study evaluated
      the contrast-enhanced CT and MR findings of the spleen in patients with systemic
      amyloidosis. METHODS: Data were extracted by reviewing pathology and radiology
      department records of the teaching hospital of Naples over 10 years, from 1
      January 1993 to 31 December 2002. Thirty-three patients with amyloidosis were
      identified, 10 of whom had a CT scan and two of whom had an MR study. The
      population-based study was composed of 12 patients with histologically proved
      amyloidosis who underwent contrast-enhanced CT or MR scan of the abdomen. The
      spleen and liver were evaluated for organ size and perfusion. RESULTS: The spleen
      was hypoperfused in nine of 12 patients. Mild splenomegaly was present in only
      one case. Hepatomegaly was associated with markedly acute left lobe margin in
      nine patients and with rounded anterior profile of segments 3 and 4 in four
      patients. Moreover, a large area of low attenuation with indefinite geographic
      margins involving the right hepatic lobe was observed in three patients.
      CONCLUSION: The finding of splenic hypoperfusion may be a marker of systemic
      amyloidosis, which represents a useful clue when clinical findings fail to
      suggest the proper diagnosis.

PMID- 16096869
TI  - Pneumatosis intestinalis after lung transplant.
AB  - Pneumatosis intestinalis may be idiopathic or associated with numerous
      conditions. Uncommonly, it has been associated with organ transplantation. We
      report one case of pneumatosis intestinalis after lung transplantation in an
      adult patient. To our knowledge, this finding has not been reported in the
      radiology literature.

PMID- 16096870
TI  - Gastrointestinal tract perforation: CT diagnosis of presence, site, and cause.
AB  - Gastrointestinal tract perforation is an emergent condition that requires prompt
      surgery. Diagnosis largely depends on imaging examinations, and correct diagnosis
      of the presence, level, and cause of perforation is essential for appropriate
      management and surgical planning. Plain radiography remains the first imaging
      study and may be followed by intraluminal contrast examination; however, the high
      clinical efficacy of computed tomographic examination in this field has been well
      recognized. The advent of spiral and multidetector-row computed tomographic
      scanners has enabled examination of the entire abdomen in a single breath-hold by
      using thin-slice sections that allow precise assessment of pathology in the
      alimentary tract. Extraluminal air that is too small to be detected by
      conventional radiography can be demonstrated by computed tomography. Indirect
      findings of bowel perforation such as phlegmon, abscess, peritoneal fluid, or an
      extraluminal foreign body can also be demonstrated. Gastrointestinal mural
      pathology and associated adjacent inflammation are precisely assessed with thin
      section images and multiplanar reformations that aid in the assessment of the
      site and cause of perforation.

PMID- 16096871
TI  - Intrapericardial bronchogenic cyst overriding the pulmonary artery.
AB  - We describe a case of a 3-year-old child with an intrapericardial bronchogenic
      cyst arising from the pericardium overlying the pulmonary artery found
      incidentally at the time of elective repair of a sinus venosus atrial septal
      defect with partial anomalous pulmonary venous return. A cystic mass overriding
      the right pulmonary artery was resected and diagnostic studies revealed multiple
      loculated cysts lined by respiratory mucosa with cartilage and smooth muscle in
      the wall consistent with a bronchogenic cyst. The cyst was completely resected
      and postoperative recovery was uneventful.

PMID- 16096872
TI  - Transcatheter occlusion of a large pulmonary arteriovenous malformation using the
      Amplatzer vascular plug.
AB  - Pulmonary arteriovenous malformation (AVM) is a rare entity with well-described
      signs, symptoms, and complications. Pulmonary AVMs can be congenital or acquired.
      They have been described in the setting of severe liver disease and after
      palliation with a Glenn shunt in which the hepatic venous blood flow has been
      excluded from the pulmonary blood flow. A variety of surgical and transcatheter
      interventions have been used to occlude AVMs. We report the use of the Amplatzer
      vascular plug to successfully occlude a pulmonary AVM in a 12-year-old patient.

PMID- 16096876
TI  - Defining clinical pharmacy and pharmaceutical care.

PMID- 16096877
TI  - The history of DES, lessons to be learned.
AB  - Since the 1940s, diaethylstilbestrol (DES) has been used by millions of pregnant
      women to prevent miscarriages and many other disorders in pregnancy. In 1971, it
      became clear that this apparently innocent treatment proved to be a time bomb for
      the infants exposed to DES during the first trimester of pregnancy. DES is now
      associated with an increased risk of breast cancer, clear cell adenocarcinoma
      (CCAC) of the vagina and cervix, and reproductive anomalies. This article
      summarises the potential long-term health implications of DES on the mother, DES
      daughters and DES sons, and the possible side effects on the third generation.
      Health care professionals have to know the history of DES to prevent future
      disasters with drugs prescribed.

PMID- 16096878
TI  - Cost-containment as part of pharmaceutical policy.
AB  - In this article the authors provide insight into the basis for price setting of
      medicines, the increasing pharmaceutical budgets in the past decades, and the
      measures governments and insures have taken to curb rising pharmaceutical costs.
      Four reasons are out lined for the fact that medicines are by some considered
      expensivey: 1) there are fundamental differences between medicines and other
      consumer products; 2) medicines are technology requiring an inordinate amount of
      research and development; 3) medicines are developed, manufactured, and
      distributed according to strict regulatory requirements; 4) medicines are most
      often selected by a physician for a specific patient and reimbursed in whole or
      in party by a third-party insurer or the state. Pharmaceuticals mean share of GDP
      has been 1.2% in OECD countries in recent decades. Pharmaceuticals accounted for
      15.4% of total health expenditure, with public spending about half of this
      amount. Since 1970, the average share of GDP for pharmaceuticals in most
      countries has increased 1.5% more per year than GDP growth. Four types of
      strategies to curb rising Pharmaceuticals costs are described and a taxonomy of
      strategies provided These are:1)price and profit controls; 2) reimbursement
      system charges; 3) other fiscal measures; 4) quality measures. Pharmaceuticals
      policy has suffered from the pervasive misunderstanding that drugs are like any
      other commodity; resulting in policy makers viewing pharmaceuticals expenditures
      without thinking about drugs in their proper content of health care. The authors
      conclude by advocating a balanced approach to policymaking in a environment of
      rising pharmaceuticals costs.

PMID- 16096879
TI  - Effects of alendronate and calcitonin on bone mineral density in postmenopausal
      osteoporotic women. An observational study.
AB  - OBJECTIVE: Alendronate and calcitonin are antiresorptive drugs that were used for
      the treatment of postmenopausal osteoporosis and were shown to increase bone
      mineral density (BMD). However, the effect of both drugs in daily clinical
      practice may differ from that observed in clinical trials. METHOD: About 50
      postmenopausal osteoporotic women were observed during their first year of
      treatment. Among them, 32 patients used alendronate and 18 used calcitonin.
      Lumbar spine and femoral neck BMD were measured by dual energy X-ray
      absorptiometry (DXA) at baseline and after 1 year of therapy. Biochemical markers
      (B-ALP--bone-specific alkaline phosphatase, OTC--osteocalcin and DPD/UCr-
      deoxypyridinoline/creatinine ratio) of bone metabolism were measured at baseline
      and 6 months later. Patient compliance was assumed by tablet counting and
      verified at interview. Each patient was further questioned about her attitude
      towards the treatment, as well as her dairy product intake, physical activity,
      use of other medications, smoking and social status. MAIN OUTCOME MEASURE: (1)
      Annual percent change in BMD in lumbar spine and femoral neck after the one-year
      treatment with either alendronate or calcitonin. (2) The change in biochemical
      markers of bone turnover. RESULTS: The lumbar spine BMD significantly increased
      by 7.0% (P < 0.001), the femoral neck BMD by 4.3% (P < 0.01). OTC, B-ALP and
      DPD/UCr decreased significantly during the therapy with alendronate. Compliance
      with therapy was 79% (95% CI 68-90%). In the calcitonin-treated group, the lumbar
      spine BMD significantly increased by 3.1 % (P < 0.05), while the femoral neck BMD
      remained unchanged. OTC, B-ALP and DPD/UCr did not change significantly during
      the treatment with calcitonin. Compliance with calcitonin therapy was 87% (95% CI
      63-110%). The annual change of BMD in both treatment groups was independent on
      all questioned factors. CONCLUSION: In daily practice, alendronate enhanced
      significantly BMD both in lumbar spine and femoral neck. Calcitonin showed
      increase only in the lumbar spine BMD.

PMID- 16096880
TI  - Characteristics associated with neuropathy and/or retinopathy in a hospital
      outpatient diabetic clinic.
AB  - BACKGROUND: The incidence of diabetes is increasing worldwide and with it the
      risk of diabetic complications. The aim of this study was to characterise
      parameters associated with neuropathy and/or retinopathy in a hospital outpatient
      diabetic clinic population. METHOD: A structured questionnaire addressing
      diabetes related factors and demography was administered to a cross-sectional
      sample of patients (n = 290) with type 1 and type 2 diabetes attending a hospital
      diabetic outpatient clinic. Additional clinical measures were obtained from
      patient medical files and computerised records. Logistic regression analysis was
      used to identify characteristics associated with the presence of complications.
      RESULTS: When controlling for other predictors, increasing age (P < 0.01), type 1
      diabetes (P = 0.05), longer duration of diabetes (P < 0.01), increased serum
      triglyceride levels (P = 0.03), HbA1c (>8%; P = 0.03), self-reported low physical
      activity levels (P = 0.05) and being a smoker (P = 0.01) were positively related
      to retinopathy and/or neuropathy. Patients within the study population had
      reasonably well controlled BP and serum lipids, thus explaining the absence of
      these particular variables from the list of predictor parameters. Other factors
      including diabetes knowledge, home blood glucose monitoring, gender, body mass
      index, clinic attendance and occupational status were not significantly
      associated with retinopathy or neuropathy in the present study population.
      CONCLUSIONS: Pharmacists and other health practitioners who are in a position to
      be involved in the care and management of patients with diabetes should raise
      awareness of complications, particularly amongst patients who present with the
      above risk factors and provide necessary counselling and advice as required.

PMID- 16096881
TI  - Managing urinary tract infections in nursing homes: a qualitative assessment.
AB  - OBJECTIVE: To elucidate the steps in the management of urinary tract infections
      (UTIs) in elderly nursing home residents, in order to derive data which would
      assist in an economic evaluation of such infections. METHOD: Maximum variation
      sampling was used to recruit General Practitioners (GPs) and nurses (who worked
      in nursing homes), into the study. Using semi-structured interviews, a topic
      guide was used to explore diagnosis, treatment and the role of GPs and nurses in
      the management of UTIs in nursing home residents. Thematic analysis was employed
      to identify the main themes. MAIN OUTCOME MEASURES: A comprehensive description
      of the management of UTIs in nursing home residents that will be used in a future
      economic evaluation of the costs of this prevalent infection in this setting.
      RESULTS: Ten GPs and nurses respectively took part in the interviews. Three
      overarching themes emerged from the interviews: information, processes and
      decision-making. Health care professionals described the key symptoms for
      diagnosis (information), testing procedures to confirm the presence of an
      infection (processes); many variations in management pathways were described. The
      nurse was central to decision-making in treatment i.e. prescribing of an
      antibiotic. Most GPs reported that they accepted the nursing staff's assessment
      of the resident and seldom visited a patient in a nursing home for a UTI.
      CONCLUSIONS: The management approach to UTIs varied greatly and was a more
      complex process than anticipated. Identification of the component steps will be
      used to perform an economic evaluation of UTIs in nursing homes.

PMID- 16096882
TI  - Infovigilance: reporting errors in official drug information sources.
AB  - INTRODUCTION: The French drug database Theriaque (http://www.theriaque.org)
      developed by the (Centre National Hospitalier d'Information sur le Medicament)
      (CNHIM), is responsible for the dissemination of independent information about
      all drugs available in France. Each month the CNHIM pharmacists report problems
      due to inaccuracies in these sources to the French drug agency. In daily practice
      we devised the term "infovigilance": "Activity of error or inaccuracy
      notification in information sources which could be responsible for medication
      errors". The aim of this study was to evaluate the impact of CNHIM infovigilance
      on the contents of the Summary of Product Characteristics (SPCs). METHOD: The
      study was a prospective study from 09/11/2001 to 31/12/2002. The problems related
      to the quality of information were classified into four types
      (inaccuracy/confusion, error/lack of information, discordance between SPC
      sections and discordance between generic SPCs). MAIN OUTCOME MEASURES: (1) Number
      of notifications and number of SPCs integrated into the database during the study
      period. (2) Percentage of notifications for each type: with or without potential
      patient impact, with or without later correction of the SPC, per section.
      RESULTS: 2.7% (85/3151) of SPCs integrated into the database were concerned by a
      notification of a problem. Notifications according to type of problem were
      inaccuracy/confusion (32%), error/lack of information (13%), discordance between
      SPC sections (27%) and discordance between generic SPCs (28%). 55% of problems
      were evaluated as 'likely to have an impact on the patient' and 45% as 'unlikely
      to have an impact on the patient'. 22 of problems which have been reported to the
      French drug agency were corrected and new updated SPCs were published with the
      corrections. CONCLUSIONS: Our efforts to improve the quality of drug information
      sources through a continuous "infovigilance" process need to be continued and
      extended to other information sources.

PMID- 16096883
TI  - Cross Hypersensitivity Syndrome between Phenytoin and Carbamazepine.
AB  - OBJECTIVE: To evaluate the incidence of cross anticonvulsant hypersensitivity
      syndrome (AHS) between phenytoin (PHT) and carbamazepine (CBZ) in hospitalized
      patients. METHOD: Retrospective chart review about the cross AHS was retrieved
      from pharmacy adverse drug reaction program from 1998 to 2002 in a 450-bed
      teaching hospital. MAIN OUTCOME MEASURES: AHS was defined as the appearance of at
      least two symptoms with the first anticonvulsant drug (ACD). Cross AHS was
      considered if after withdrawal of a first ACD because of hypersensitivity
      symptoms, a new episode with similar or new symptoms appeared after exposure to a
      second ACD. The following symptoms were considered- rash, fever, hepatotoxicity,
      lymphadenopathies or hematological disturbances. RESULTS: Cross AHS between PHT
      and CBZ was observed in nine cases (45). After the cross-reaction event, four of
      them were treated with valproic acid, two with vigabatrin, two with phenobarbital
      and one with no treatment without developing further AHS. CONCLUSIONS: AHS is a
      severe complication of aromatic ACD that can compromise the future choice of
      therapy. Because of the high incidence of clinical cross-reaction between these
      two drugs, non-aromatic ACD alternatives, must be considered.

PMID- 16096884
TI  - Actual and perceived provision of pharmaceutical care in Danish community
      pharmacies: the pharmacists' opinions.
AB  - OBJECTIVE: The study explores characteristics of community pharmacies with
      respect to implementing pharmaceutical care activities. The article addresses the
      provision of pharmaceutical care at reality level, perceived level and policy
      level. METHOD: A cross-sectional questionnaire was sent to all Danish community
      pharmacies to investigate the provision of pharmaceutical care (n=288). The
      respondents were pharmacists. Pharmaceutical care activities were operationalised
      by detecting and identifying medicine-related problems, setting goals to solve
      medicine-related problems, and documenting efforts to solve them. A non
      respondent analysis was also performed. MAIN OUTCOME MEASURE: The identification
      of medicine-related problems (from self-report) was used as a proxy measure of
      pharmaceutical care activities and compared to pharmacies' self-reported
      provision of pharmaceutical care. RESULTS: The survey response rate was 75.7. The
      characteristics of pharmacies that detected medicine-related problems differed
      from those of pharmacies with only a perceived provision of pharmaceutical care.
      Pharmacies that actually detected medicine-related problems focused on external
      cooperation regarding their pharmacy activities. CONCLUSION: The profiles of the
      perceived providers of pharmaceutical care and the respondents that detected
      medicine- related problems were distinct, thus indicating two separate groups of
      pharmacies. Pharmaceutical care has only been implemented in Denmark to a limited
      extent. This may be explained in part by the top-down implementation strategy
      conceived by the proprietor organisation.

PMID- 16096885
TI  - The frequency and potential causes of dispensing errors in a hospital pharmacy.
AB  - OBJECTIVES: To determine the frequency and types of dispensing errors identified
      both at the final check stage and outside of a UK hospital pharmacy, to explore
      the reasons why they occurred, and to make recommendations for their prevention.
      METHOD: A definition of a dispensing error and a classification system were
      developed. To study the frequency and types of errors, pharmacy staff recorded
      details of all errors identified at the final check stage during a two-week
      period; all errors identified outside of the department and reported during a one
      year period were also recorded. During a separate six-week period, pharmacy staff
      making dispensing errors identified at the final check stage were interviewed to
      explore the causes; the findings were analysed using a model of human error. MAIN
      OUTCOME MEASURES: Percentage of dispensed items for which one or more dispensing
      errors were identified at the final check stage; percentage for which an error
      was reported outside of the pharmacy department; the active failures, error
      producing conditions and latent conditions that result in dispensing errors
      occurring. RESULTS: One or more dispensing errors were identified at the final
      check stage in 2.1% of 4849 dispensed items, and outside of the pharmacy
      department in 0.02% of 194,584 items. The majority of those identified at the
      final check stage involved slips in picking products, or mistakes in making
      assumptions about the products concerned. Factors contributing to the errors
      included labelling and storage of containers in the dispensary, interruptions and
      distractions, a culture where errors are seen as being inevitable, and reliance
      on others to identify and rectify errors. CONCLUSION: Dispensing errors occur in
      about 2% of all dispensed items. About 1 in 100 of these is missed by the final
      check. The impact on dispensing errors of developments such as automated
      dispensing systems should be evaluated.

PMID- 16096886
TI  - A survey of the provision of clinical pharmacy services in relation to existing
      published standards.
AB  - OBJECTIVE: To investigate the provision of clinical pharmacy services in
      hospitals in one NHS region in UK, and to measure the delivery of these services
      against published standards. METHOD: The study comprised two phases. Phase 1 was
      a postal questionnaire to hospital chief pharmacists seeking information on the
      provision of clinical pharmacy in their hospital. Phase 2 involved a semi
      structured interview with hospital chief pharmacists to obtain a detailed
      understanding of clinical pharmacy services in their hospital and factors
      influencing the provision of these services. RESULTS: Ninety-four percent of all
      hospitals surveyed were providing a clinical pharmacy service. However, only two
      thirds provided a service to all wards, and the main reason given for not doing
      so, was lack of resources. There was a divergence of opinion amongst chief
      pharmacists whether it was better to provide a limited service to all wards or a
      good service to some wards. Thirty-seven percent of hospitals did not meet the
      minimum standard of frequency for visiting acute wards, whereas, 58 were meeting
      the optimal standard of frequency of visits for non-acute short stay wards and 67
      for long stay wards, primarily because the latter required less frequent
      visiting. The study showed that hospital pharmacies were influencing prescribing
      decisions in a variety of ways other than ward visiting. CONCLUSION: Although
      hospital chief pharmacists see clinical pharmacy as a core service, published
      standards for these services are not being met. As a result of staff shortages,
      managers are using a variety of approaches to maintain clinical pharmacy
      services. There is scope for further devolvement of duties to pharmacy
      technicians in order to release valuable pharmacist time.

PMID- 16096887
TI  - Methylphenidate: use in daily practice.
AB  - OBJECTIVE: With the aim of getting more insight into compliance of children using
      methylphenidate, we studied the day-to-day use of the drug. In addition, the
      efficacy and side effects of treatment, stopping, switching to other drugs and
      the use of additional psychoactive drugs in daily practice were studied. METHOD:
      On the basis of pharmacy records, the use of methylphenidate by 52 children was
      studied. Two parameters for compliance were calculated. By means of a
      questionnaire, parents were asked about their children's compliance with the use
      of methylphenidate as well as about their experience with treatment. MAIN OUTCOME
      MEASURE: Compliance, use of methylphenidate in weekends and holidays, self
      reported efficacy, side effects, stopping and switching to other drugs. RESULTS:
      Depending on the parameter calculated, the percentage of children with a good
      compliance varied from 25 to 47%. About 65% of the children used less or no
      methylphenidate in the weekends and holidays. Sixty-five percent of the parents
      reported to pass over a dose once in a while. According to 61% of the parents (n
      = 28) the efficacy of methylphenidate was good or very good. Nine (33%) of 28
      children stopped using methylphenidate. Seven children stopped using the drug
      because of side-effects or lack of efficacy. Seven children switched to other
      psychoactive drugs. Fifty-seven percent of all children used additional
      psychoactive drugs. CONCLUSION: The percentage of children having a good
      compliance calculated on the basis of pharmacy records is rather low. This is
      partly the result of the decreased use of methylphenidate in the weekends and
      holidays.

PMID- 16096889
TI  - Attitudes of Nigerian pharmacists towards pharmaceutical care.
AB  - OBJECTIVE: To explore Nigerian pharmacists' attitudes towards pharmaceutical
      care, and determine significant attitudinal differences in different practice
      settings. METHOD: A 25-item self-completion pre-tested and validated
      questionnaire was administered to a convenience sample of 1500 pharmacists in
      Nigeria. Data were gathered on a Likert-type rating scale. Descriptive statistics
      including frequencies and mean scores, and significant attitudinal differences on
      sample characteristics were computed. MAIN OUTCOME MEASURE: Pharmacists' opinions
      on multi-item pharmaceutical care attitudinal scale. RESULT: The national survey
      achieved 67% response rate. About three-quarters (76%, n = 1005) of the
      respondents indicated willingness to embrace pharmaceutical care. Nearly all the
      pharmacists (96%) believed pharmaceutical care would enhance patients'
      appreciation of the pharmacist and 84% reported their intention to practice
      pharmaceutical care even if there is no additional income. An overwhelming 93%
      said that they would participate in any training program to enable them to
      practice pharmaceutical care, while less than a quarter (20%) claimed their
      pharmacy layout was suited for patient-centered practice. Three quarters (75%) of
      the respondents indicated positive attitude towards pharmaceutical care. Both
      male and female genders, all age groups, different levels of professional
      experience, and pharmacists in hospital, community, industrial and administrative
      practice settings had similar positive attitude scores. Only pharmacists'
      professional experience appeared to have a significant influence on attitude
      scores (F = 5.267; P = 0.001), with scores varying with the level of professional
      experience. CONCLUSION: The study has shown that the attitudes of Nigerian
      pharmacists towards pharmaceutical care are favorably high irrespective of the
      practice settings. The attitude ratings vary with the levels of professional
      experience, with pharmacists having less experience showing more positive
      attitude. Nigerian pharmacists indicated willingness to implement pharmaceutical
      care but expressed major concerns about their knowledge, professional skills, and
      pharmacy layout. Gradual introduction of pharmaceutical care would be logical.

PMID- 16096888
TI  - Implementation of a pharmacist-led clinic for hypertensive patients in primary
      care--a pilot study.
AB  - OBJECTIVES: To implement a pharmacist-led Hypertension Management Clinic in one
      general medical practice. To evaluate the impact of the clinic on blood pressure
      (BP) control and prevention of coronary heart disease (CHD). METHOD: A total of
      242 patients attended the pharmacist-led hypertension clinic over a 10-month
      period. Lifestyle and drug therapy alterations were implemented to achieve
      British Hypertension Society (BHS) target level BP. A sub-group of 160 patients
      were used to compare BP control in the clinic setting against that with the
      general practitioner (GP). Assessment was made of 10-year CHD risk in patients
      with no artherosclerotic disease. Patients with underlying artherosclerotic
      disease were prescribed statins, and antiplatelet drugs where indicated. MAIN
      OUTCOME MEASURES: Changes in numbers of hypertensive patients meeting the BHS
      target level BP. Changes in prescribing of antiplatelet agents and statins for
      primary and secondary prevention of artherosclerosis. RESULTS: In 206 patients
      with established hypertension, the number achieving target level BPs increased
      from 74 (36%) pre-clinic to 174 (85%) post-clinic; P < 0.001 chi-squared test.
      After attending the clinic, for 5 months 74 patients (80%) achieved target level
      BP in the clinic compared with 27 (40%) with standard GP care; P < 0.001 chi
      squared test. Of 188 patients assessed for primary prevention therapy, 126 (67%)
      required treatment with aspirin and 37 (20%) with a statin. Post-clinic 101 (80%)
      received aspirin compared with 17 (13%) pre-clinic and 34 (92%) received a statin
      in comparison with 4 (11%) pre-clinic; both P < 0.001 chi-squared test.A total of
      52 (96%) of 54 patients received an antiplatelet agent for secondary prevention
      of artherosclerosis compared with 40 patients (74%) pre-clinic. Thirty six of 54
      patients required a statin for secondary prevention. Thirty five patients (97%)
      received a statin compared with 23 (64%) pre-clinic; both P < 0.01 chi-squared
      test. CONCLUSION: Implementation of a pharmacist-led clinic improved blood
      pressure control and appropriate prescribing of antiplatelet agents and statins
      for primary prevention of CHD and secondary prevention of artherosclerosis.

PMID- 16096890
TI  - Hospital pharmacists' awareness of a new antibiotic guideline in the UK:
      implications for practice.
AB  - OBJECTIVES: Pharmacists play an important role in the review of local hospital
      guidelines. British Thoracic Society (BTS) guidelines for the management of
      patients with community-acquired pneumonia (CAP) were updated in 2001, and it is
      important that individual hospital recommendations are based upon this national
      guidance. The aim of this study was to identify UK Chief Pharmacists' awareness
      of these updated guidelines one year after their publication. Secondary aims were
      to identify whether pharmacists had subsequently initiated revision of
      institutional CAP guidelines, and what roles different professional staff had
      performed in this process. METHOD: A self-completion postal questionnaire was
      sent to the Chief Pharmacist (or their nominated staff) in 253 UK NHS hospitals
      in November 2002. This aimed to identify issues relating to their awareness of
      the 2001 BTS guidelines and subsequent revision of their hospital's guidelines.
      RESULTS: 188 questionnaires were returned (a response rate of 74%), of which 164
      hospitals had local antibiotic prescribing guidelines. Respondents in 29% of
      these hospitals were unaware of the 2001 BTS publication and institutional
      guidelines had been revised in only 51% of hospitals where the Chief Pharmacist
      was purportedly aware of the new BTS guidance. Generally, more staff types were
      involved in revising guidelines than initiating revision. CONCLUSIONS:
      Variability existed in both Chief Pharmacists' awareness of new national guidance
      and subsequent review processes operating in individual hospitals. A lack of
      proactive reaction to new national guidance was identified in some hospitals, and
      it is hoped that the establishment of specialist "infectious diseases
      pharmacists" will facilitate the review of institutional antibiotic prescribing
      guidelines in the future.

PMID- 16096891
TI  - Use of medicines that influence falls or fractures in a residential home setting.
AB  - OBJECTIVE: To study the pattern of use of medicines that may contribute to, or
      protect against, falls and fractures in the setting of a UK residential home
      population, and to compare the results with a similar study conducted in 2001.
      SETTING AND METHOD: A cross-sectional survey was conducted in 2003 in 18
      residential homes. A trained community pharmacist visited the homes to retrieve
      information about use of medicines whilst demographic details were provided by
      the residential home staff. MAIN OUTCOME MEASURE: The proportion of patients who
      were prescribed medicines with a potential positive benefit in preventing
      fractures, and medicines that may cause elderly people to fall. RESULTS: The
      study population consisted of 581 residents. Compared to the 2001 study, the use
      of both calcium and vitamin D had increased significantly (8.3% versus 2.1%).
      Although, the overall prescribing of psychotropics in 2003 was relatively low,
      there was a trend for increased prescribing of these medicines which have been
      identified as risk factors for falling. CONCLUSION: In a residential home setting
      in the UK, the use of psychotropic drugs is not uncommon, whereas there is
      limited use of drugs that have the potential for preventing morbidity associated
      with falls.

PMID- 16096892
TI  - "We are white coats whirling round"--moral distress in Swedish pharmacies.
AB  - OBJECTIVE: The extended role of pharmacists has made pharmacy practice more
      complex and increased the moral responsibility of pharmacy staff. Consequently,
      ethics has become an important part of their daily work. In health care, ethical
      dilemmas have been shown to cause distress, usually referred to as "moral
      distress". Moral distress among hospital personnel has been well described and
      discussed in numerous studies. There are very few similar studies in pharmacy
      settings. This article reports on the results of an investigation concerning
      whether and in what situations moral distress is present in pharmacy practice.
      METHOD: A questionnaire derived from focus group data, covering ethically
      troubling situations in pharmacy settings, was distributed to all staff of three
      pharmacies in Sweden. RESULTS: The results show that moral distress is
      experienced in the day-to-day pharmacy practice, and that it is in many ways
      connected to care providing. For example, prioritizing between customers was
      reported as very stressful. Younger personnel reported higher moral distress than
      their older colleagues did. However, there were no differences between
      pharmacies. A lack of support structures, such as meetings where ethical issues
      can be discussed, was reported by all the participating pharmacies. CONCLUSION:
      It is reasonable to assume that moral distress is even more present in pharmacy
      practice than in other health care areas as it is, in general, much more
      sensitive and exposed to the modern, demanding customer. The meeting with the
      customer is on a more neutral ground than in, for example, a hospital setting.
      Although there are ethical codes for pharmacists, they are not enough. Moral
      distress is experienced anyway; general codes and personal coping strategies must
      be supplemented with support from the management and work organization. There is
      a need to look more closely at specific factors related to the degree and
      extension of moral distress, going beyond individual coping strategies.

PMID- 16096893
TI  - Outpatient use of systemic antibiotics in croatia.
AB  - OBJECTIVE: The aim was to estimate the outpatient utilization of antibacterials
      for systemic use in Zagreb, Croatia, and to define the antibiotic utilization
      characteristics and consequences. METHOD: Using the WHO ATC/DDD methodology, the
      number of defined daily doses per 1000 inhabitants per day (DDDs/TID) was
      calculated for each individual antibiotic and ATC system levels were calculated
      from data collected on the number and size of packages prescribed and dispensed
      from pharmacies. The Drug Utilization 90% (DU90%) method was used to evaluate the
      quality of drug prescribing. RESULTS: The total utilization of antibiotics was
      found to be extremely high, 55.0 DDDs/TID. The leading antibiotic was amoxicillin
      + clavulanic acid with 14.7 DDDs/TID. Penicillins accounted for the highest
      utilization (46.3%) expressed in DDDs/TID (25.4), followed by cephalosporins and
      macrolides 25 and 12.5% of utilization, respectively expressed in DDDs/TID),
      tetracyclines, quinolones, aminoglycosides and other agents. Nine of 27
      antibiotics fell within the DU90% segment. The cost/DDD foldrugs within DU90%
      segment was 1.2 EUR, for drugs beyond DU90% segment was 1.4 EUR, and the average
      was 1.2 EUR. CONCLUSION: Irrational prescribing and preference to more expensive
      drugs have been reported in Zagreb. Therefore, the risk of resistance of
      microorganisms to beta-lactamase antibiotics, macrolides and quinolones could be
      expected. Prescribing patterns should be changed by introducing national
      guidelines on rational antibiotic prescribing, monitoring and evaluation of their
      implementation. Additional continuing education of physicians and pharmacists
      from independent sources should be organized and proper education should be
      provided to patients.

PMID- 16096894
TI  - Health professionals: how do they assess new medicines?
AB  - OBJECTIVE: To identify the types of information used by health professionals when
      assessing a new medicine, and to discover whether measures of clinical
      effectiveness and cost-effectiveness are understood and used. METHOD: A cross
      sectional survey of 56 health professionals was undertaken in a tertiary hospital
      in New Zealand. Respondents were consultants, registrars, house-surgeons,
      pharmacists, and specialist nurses MAIN OUTCOME MEASURES: Health professionals'
      opinions on clinical and cost information required for assessing a new medicine;
      their ability to calculate measures of risk; and their ability to define clinical
      effectiveness, cost-effectiveness and types of economic analysis. RESULTS: Thirty
      four percent of respondents considered journals and research to be the most
      accurate sources of information when assessing a new medicine. Efficacy, safety,
      contraindications and side-effects were the most important information sought. In
      total, 93% gave an acceptable definition of clinical effectiveness, and 38% of
      cost-effectiveness. The majority of each profession (except specialist nurses)
      could calculate relative risk reduction (RRR) and absolute risk reduction (ARR)
      but fewer could calculate numbers needed to treat (NNT). Eighty-four percent of
      respondents felt that cost affected their assessment of a new medicine. Less than
      a quarter of respondents could define each type of economic analysis. Consultants
      and pharmacists appeared to have the best knowledge of economic analysis.
      CONCLUSION: Efficacy, safety, contraindications and side-effects were the most
      important information sought when assessing a new medicine. Health professionals'
      knowledge of clinical effectiveness was greater than their knowledge of cost
      effectiveness. Consultants and pharmacists appeared to have the best knowledge of
      economic analysis.

PMID- 16096895
TI  - Cost-effectiveness of thrombolytics: a simplified model.
AB  - OBJECTIVE OF THE STUDY: To construct a simple model for an internal,
      retrospective cost-effectiveness analysis and to calculate the incremental cost
      effectiveness of tissue plasminogen activator (TPA) over streptokinase (SK) in
      Turkey. SETTING: Kosuyolu Heart, Education and Research Hospital, Istanbul,
      Turkey. METHOD: Among patients who were hospitalized for treatment of acute
      myocardial infarction (AMI), 196 were randomly selected. One-year mortality rates
      according to the treatment groups (TPA, SK, other) were determined. Among
      surviving patients, 28 from TPA and another 28 from SK group were randomly
      selected for the pharmacoeconomic analysis. Patient treatment data were taken
      from medical records while data regarding to costs were taken from hospital
      bills. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER). The
      cost part of the ratio was considered as 'the overall-costs', while the
      effectiveness part was considered as 'lives saved' per treatment group. RESULTS:
      With an increased one-year survival rate of 2.37% and an increased cost of euro
      1120.8 ($1165.6) per patient in the TPA group, the ICER for the use of TPA
      instead of SK was euro 47,289 ($49,180.6) per life saved. CONCLUSION: This model
      can be a guide for similar analyses. The results of our study (the incremental
      cost-effectiveness of TPA over SK) will be informative for the decision-makers in
      Turkey, by whom the medical benefit for money spent would be assessed and judged.
      We believe that our results make a contribution to similar studies in the
      literature.

PMID- 16096896
TI  - A clinical and economic study of community-acquired pneumonia between single
      versus combination therapy.
AB  - BACKGROUND: Pneumonia is one of the leading causes of morbidity and mortality
      among children in many developing countries. It is reported that 12.9 million
      children under 5 years of age died world-wide in 1990 and one-third of these
      deaths or 4.3 million annually were attributed to acute respiratory infection
      with pneumonia. OBJECTIVES: On this basis, a study was conducted in a district
      hospital to study the therapy outcomes of antibiotic regimens used in pediatric
      community-acquired pneumonia (CAP) management and to conduct a cost-effectiveness
      analysis (CE) between IV ampicillin versus combination therapy of IV ampicillin
      and IV gentamicin. METHOD: A prospective, randomized, controlled, single blind
      study was conducted in a pediatric ward in a 80-bed district hospital. Pediatric
      patients diagnosed with CAP aged 2 months to 5 years old were randomly and
      equally divided into two treatment arms: ampicillin versus ampicillin plus
      gentamicin. The dose of IV ampicillin used in this study was 100 mg/kg/day
      divided every 6 h and 5 mg/kg of IV gentamicin as a single daily dose. Both
      clinical and economic evaluations were carried out to compare both treatment
      arms. RESULTS: With the inclusion and exclusion criteria, only 40 patients
      diagnosed with CAP were included in the study. The results showed that the two
      treatment arms were significantly different (P < 0.05) in terms of duration of
      patients on ampicillin, number of days of hospitalization and time to switch to
      oral therapy. A significant difference was noted between the two treatment
      modalities in terms of effectiveness and cost (P < 0.05). CONCLUSION: Overall,
      the endpoint of this study showed that the total cost per patient of ampicillin
      treated group is cheaper than the total cost with the combination therapy
      (ampicillin plus gentamicin) and reduced unnecessary exposure to adverse effects
      or toxicities. Besides that, addition of gentamicin in the treatment modalities
      will only increase the cost of treatment without introducing any changes in the
      treatment outcome.

PMID- 16096897
TI  - When fever, paracetamol? Theory and practice in a paediatric outpatient clinic.
AB  - OBJECTIVE: To determine how medical and nursing staff treat feverish children and
      compare the findings with their theoretical knowledge, evaluating how they might
      contribute to fever phobia in parents. SETTING: Paediatric Emergency Department.
      METHOD: In the first step, we analysed prospectively the files of all children
      having consulted the Paediatric Emergency Department with a history of fever or
      of body temperature above 38 degrees C during a 2-week period. The second step
      consisted of evaluating knowledge and perception of fever of doctors and nurses
      using a questionnaire. MAIN OUTCOME MEASURES: Prospective study: final diagnosis
      (viral, non- invasive bacterial disorders, invasive bacterial disorders), site of
      measurement and average temperature. Evaluation of theoretical knowledge:
      definition of fever, site of measurement, evaluation of the child's clinical
      state, antipyretic drug choice. RESULTS: A total of 114 children under 5 years of
      age were enrolled and 24 caregivers (12 doctors, 12 nurses, 90 of the staff)
      responded to the questionnaire. The results showed good consistency in
      theoretical knowledge, but an excessive fear about cerebral damage was also shown
      by doctors. This belief likely contributes to the transmission of fever phobia to
      parents. In contrast, analysis of children management showed that fever was often
      under-treated, especially by nurses and even more so by parents. Paracetamol
      remained the first-line antipyretic drug yet was often administered in
      insufficient doses. Non-steroidal anti-inflammatory drugs were seldom used,
      except by parents (16 of all the children). Contrary to literature, the favourite
      route of administration was the rectal one. Physical methods like sponging were
      largely used by nurses, despite the uncertainties in their real effectiveness and
      their known side-effects. CONCLUSION: Our study showed that the management of
      feverish children was globally correct in the Paediatric Emergency Department,
      but several improvement measures have been taken (e.g. tables of normal and
      abnormal ranges of temperature, recommended temperature measurement techniques,
      dosage regimen of antipyretic drugs, guidelines to parents), justifying the
      implementation of a pharmaceutical follow-up.

PMID- 16096898
TI  - Use of antiplatelet drugs in the stroke unit of a Hong Kong hospital.
AB  - OBJECTIVE: Antiplatelet drugs are widely used for secondary prevention of
      thrombotic cerebrovascular disease. The antiplatelet prescribing patterns has
      been evaluated in several studies but data about Hong Kong patients are lacking.
      This study is to investigate the prescribing patterns of antiplatelet agents in a
      Hong Kong hospital. METHOD: All patients over 18 years, who attended the stroke
      unit between 1 October 2002 and 31 December 2002 and were on antiplatelet therapy
      were included in the study. Data were collected through retrospective chart
      review and recorded on a standardized data collection form. Continuous and
      categorical data were expressed as mean and counts respectively. Factors that
      determine frequency and pattern of antiplatelet therapy were assessed in multiple
      logistic regression models. RESULTS: Three hundred and nineteen patients were
      included in the study. Aspirin and clopidogrel accounted for 82.1 and 16.3 of all
      prescriptions respectively and remaining patients were on aspirin/dipyridamole.
      Patients with no history of aspirin use were less likely to be treated with
      clopidogrel compared with those experienced aspirin intolerance (OR=0.004, 95 CI
      0.000-0.051). Patients with history of gastrointestinal (GI) diseases were more
      likely to receive clopidogrel than those had no history of GI disorders
      (OR=154.86, 95 CI 33.76-710.38). Atrial fibrillation (AF) was positively
      associated with clopidogrel prescription (OR=11.83, 95 CI 1.21-115.85). In
      addition, patients with concomitant gastroprotective drugs received clopidogrel
      significantly less often than those without gastroprotective agents (OR=0.06, 95
      CI 0.01-0.29). CONCLUSION: Use of antiplatelet agents in patients receiving
      antiplatelet therapy of the stroke unit has complied with existing evidences.
      Several factors that determine choice between aspirin and clopidogrel were
      identified which included history of aspirin use and GI disorders, AF and co
      prescribed gastroprotective drugs.

PMID- 16096899
TI  - Antidiabetic drug utilization in hungary.
AB  - OBJECTIVE: To evaluate the utilization trends of antidiabetics in Hungary.
      METHOD: The analysis includes the drugs of antidiabetic therapy which were
      registered between 1998 and 2002 in Hungary. The consumption of antidiabetic
      drugs was analyzed by the ATC/Defined Daily Dose (DDD) method. The data used in
      this study were derived from the National Health Insurance and from MIS
      Consulting Company. RESULTS: Between 1998 and 2002, the total consumption of
      antidiabetics increased by 41.8%, and reached 47.59 DDD/1000 inhabitants/day in
      2002. The consumption of oral antidiabetics (OAD) increased by 33.41% (33.86
      DDD/1000 inhabitants/d ay in 2002), while in the case of insulin the increase was
      67.8% (13.74 DDD/1000 inhabitants/day). Sulphonylureas were the most frequently
      used class (21.11 DDD/1000 inhabitants/day in 2002). Glibenclamide was the most
      frequently used antidiabetic drug (12.63 DDD/1000 inhabitants/day in 2002).
      CONCLUSION: The insulin class had greater emphasis in therapy. Among OAD, the
      consumption rate of sulphonylureas decreased and the consumption rate of
      Biguanides and acarbose increased. By 2002 metformin replaced 90% of the buformin
      in use. The limited effect of therapeutic recommendations could explain these
      changes, although the out-of-date buformin and the non-micronized glibenclamide
      were still in use in 2002.

PMID- 16096901
TI  - NRAMP1 polymorphism in a hybrid population between Japanese and Taiwanese
      macaques in Wakayama, Japan.
AB  - A macaque population produced by the hybridization of native Japanese macaques
      (Macaca fuscata) and introduced Taiwanese macaques (M. cyclopis) in Wakayama
      Prefecture was shown to possess three DNA haplotypes of the natural resistance
      associated macrophage protein 1 (NRAMP1). Based on genotyping and comparison with
      M. fuscata populations, it was revealed that the introduced M. cyclopis
      population was polymorphic for the NRAMP1 locus. Extensive crossbreeding of the
      introduced species with the native species was confirmed using this genetic
      marker and the proportion of M. cyclopis genes was 57.4%. Results of statistical
      tests suggested non-random mating in the hybrid population.

PMID- 16096902
TI  - The century-long pilgrimage of bradykinin B2 receptor antagonists.

PMID- 16096903
TI  - American Chemical Society--219th national meeting. 26-30 March 2000, San
      Francisco, CA, USA.

PMID- 16096904
TI  - Division of Medicinal Chemistry--second poster session and general papers.

PMID- 16096905
TI  - General sessions I.

PMID- 16096906
TI  - Award symposia.

PMID- 16096907
TI  - New prospects in anticancer agents for the 21st Century I.

PMID- 16096908
TI  - New prospects in anticancer agents for the 21st Century II.

PMID- 16096909
TI  - General sessions II.

PMID- 16096910
TI  - Chemokine antagonists as anti-inflammatory and antiviral agents I.

PMID- 16096911
TI  - Chemokine antagonists as anti-inflammatory and antiviral agents II.

PMID- 16096912
TI  - Case studies in drug development.

PMID- 16096913
TI  - Selective estrogen receptor modulators.

PMID- 16096914
TI  - Oligonucleotide and carbohydrate therapeutics.

PMID- 16096915
TI  - Division of chemical information.

PMID- 16096917
TI  - American Academy of Allergy, Asthma and Immunology--56th annual meeting. 3-8
      March 2000, San Diego, CA, USA.

PMID- 16096916
TI  - Japanese Pharmacological Society--73rd annual meeting. 23-25 March 2000,
      Yokohama, Japan.

PMID- 16096918
TI  - Asthma therapy.

PMID- 16096919
TI  - Beta2 agonists, corticosteroids and anticytokines.

PMID- 16096921
TI  - Anti-inflammatory drugs.

PMID- 16096920
TI  - Cytokines and cytokine therapy.

PMID- 16096922
TI  - Advances in understanding drug allergy.

PMID- 16096923
TI  - Neuroprotection and neurorepair. 2-4 March 2000, Magdeburg, Germany.

PMID- 16096924
TI  - Future pain drugs. 8-9 March 2000, London, UK.
AB  - Closing the gaps between product design and delivery of analgesic drugs, and
      individual patient needs for pain relief was the focus for this meeting. The
      changes in theories of nociceptive activity, from a mechanistic to a
      biopsychosocial disorder with diverse systemic modulation, were highlighted by
      Mark Travers (Janssen-Cilag, Titusville, NJ, USA), including examples from
      clinical trials where a patient's expectations were not met and high drop-out
      rates occurred. The need to target drug design and delivery to defined patient
      groups was clearly an important issue. The potential for drug delivery systems,
      such as polymer matrix and transmucosal applications, was discussed. Analogs of
      naturally occurring compounds that interact with nociceptive systems are creating
      opportunities for novel antinociceptive and anti-hyperalgesic peptides. The never
      ending discovery of new pain transmission and transduction mechanisms fuels the
      potential for synthesis of more compounds. In reality, the multifactorial nature
      of pain, with its large potential commercial market in hospitals and within the
      community, demands a similar multidimensional approach to pain therapies. Much of
      the emerging preclinical data suggest that interactions between the processes of
      nociception and the modulatory, inhibitory, immune and inflammatory systems that
      may generate or maintain nociceptive activity, may be important for the future
      development of therapeutics in pain management. Such data are being generated
      through studies with, for example: the tripeptides, vanilloid, galanin and
      neuropeptide Y receptor ligands; the pharmacological effects of sumatriptan
      (Glaxo Wellcome plc); and, the serotonin and norepinephrine selective
      antidepressant, venlafaxine (Effexor XR; Wyeth-Ayerst International Inc).

PMID- 16096925
TI  - American College of Rheumatology Spring Clinical Meeting 2000. 10-12 March 2000,
      New Orleans, LA, USA.
AB  - The spring clinical meeting was independently planned by the American College of
      Rheumatology (ACR) CME Committee and the ACR Professional Meetings Committee.
      This meeting was intended to provide an update of knowledge in the broad field of
      rheumatology through appropriate reviews of established concepts from a clinical
      perspective. Mini-symposia on the advancements in osteoporosis and bone diseases
      and practical approaches to uncommon rheumatic syndromes, were attractive
      features of this meeting.

PMID- 16096926
TI  - Recent advances in estrogen receptor antagonists.

PMID- 16096927
TI  - HLA-binding peptides as a therapeutic approach for chronic HIV infection.
AB  - Herein, we describe the Epimmune approach to prophylaxis and development of a
      multi-epitope vaccine for immunotherapy of HIV-1 infection. The central strategy
      of our program is to induce cellular immune responses, cytotoxic T-lymphocytes
      (CTL) and helper Tlymphocytes (HTL), specific for conserved epitopes from both
      structural and regulatory proteins of HIV-1. The HIV-1 derived and HLA-restricted
      CTL and HTL epitopes needed to design and construct the experimental vaccines are
      now known and allow for broad and non-ethnically biased coverage of the human
      population. The design optimization of an epitope-based DNA vaccine and
      evaluating methods for various DNA vaccine delivery technologies for possible use
      in clinical trials are addressed.

PMID- 16096928
TI  - Cardiac-derived stem cells.
AB  - Current scientific dogma holds that cardiomyocyte stem cells do not exist in the
      adult mammalian heart, and furthermore, that there is little, if any, potential
      for the regeneration of damaged myocardium. In order to approach this topic, I
      have begun with a brief overview of advances in stem cell research in other organ
      systems, such as the bone marrow and the brain. Very recent progress in cardiac
      stem cell research is then discussed, which indicates that a cardiomyocyte
      progenitor cell contributes to cardiomyocyte replacement throughout life. This
      progenitor cell may reside in the heart itself, or derive from a circulating
      marrow stem cell.

PMID- 16096929
TI  - CPC-211 (Questcor).
AB  - CPC-211 is under development by Questcor (formerly Cypros) as a potential
      treatment for stroke and closed head injury. Phase II trials have commenced for
      both indications. In June 1999, it was granted Orphan Drug status [329979]. In
      July 1998, CPC-211 received expedited development status by the FDA, following a
      review of the company's data and clinical plan for the development of CPC-211 to
      treat acute head injury [291130]. CPC-211 stimulates the action of pyruvate
      dehydrogenase, reducing the build up of lactic acid which may cause brain damage
      after stroke. It diverts the lactate production into acetyl-CoA which is a
      beneficial metabolite. CPC-211 crosses the blood-brain barrier. Preclinical
      studies involving both stroke and head injury models have shown that CPC-211 (25
      to 200 mg/kg iv) effected a significant reduction in brain lactate levels
      [328231].

PMID- 16096930
TI  - E-5842 (Laboratories Dr Esteve).
AB  - Esteve is developing E-5842, a sigma1 opioid receptor ligand, as a potential
      therapy for psychosis. It has completed phase I trials [344879,346244]. As of May
      1999, the site and protocol for phase II schizophrenia trials in the UK had been
      finalized and these were scheduled to begin shortly thereafter, with results
      likely to be available by the end of 2000 [365516]. E-5842 acted as an atypical
      antipsychotic in preclinical neurochemical and behavioral tests. Both acute (40
      mg/kg ip for 2 h) and chronic (20 mg/kg ip daily for 21 days) administration of E
      5842 increased PLC activity and the drug may thus achieve its antipsychotic
      effects via a signalling pathway involving phosphoinositide second messengers
      [336324]. E-5842 has a K(i) value of 4 nM at the sigma receptor [306875]. It
      blocks apomorphine-induced climbing, and antagonizes amphetamine-induced
      locomotor activity in mice [271405].

PMID- 16096931
TI  - Transgenic antithrombin III (Genzyme).
AB  - ATIII LLC, a joint venture between Genzyme Transgenics (GTC) and Genzyme General,
      is developing transgenic recombinant human antithrombin III (rhAT-III) as a
      potential treatment for sepsis and other disorders involving thrombosis. It is in
      phase III clinical trials in the US and Europe as an anticoagulant in patients
      undergoing elective cardiac surgery requiring cardiopulmonary bypass (CPB). GTC
      has a license from Behringwerke (Hoechst Marion Roussel; now Aventis Pharma) to
      develop transgenic AT-III. Behringwerke retains exclusive worldwide marketing
      rights to the product, but has to purchase its entire supply of transgenic AT-III
      from GTC [156364]. In March 1997, GTC signed an agreement with SMIG, a joint
      venture formed by GTC and Sumitomo Metals, under which SMIG has the rights to
      develop rhAT-III in Asia in return for US dollar 4.4 million in additional
      funding for the continued transgenic development of rhAT-III. The dollar 4.4
      million will be paid upon reaching certain milestones, which GTC expected to
      complete in 1997 [240202]. In December 1998, US-05843705 was issued covering rhAT
      III production in transgenic goats [302263]. In January 2000, the results of the
      European phase III trial, which were significant in meeting the trial's primary
      endpoint of reduction in the use of fresh frozen plasma were reported. The trial
      was also significant in two of three secondary endpoints, maintenance of normal
      AT-III levels and changes in D-dimer and fibrin monomer [352041,353372]. Three
      phase III trials were initiated in the second quarter of 1998. Two identical
      trials, one in Europe and one in the US, evaluated the safety and efficacy of
      rhAT-III compared to placebo in restoring heparin sensitivity to heparin
      resistant patients scheduled for elective cardiac surgery requiring CPB. The
      third trial, in both the US and Europe, will determine whether rhAT-III matches,
      at equivalent doses, the ability of plasma-derived AT-III to restore heparin
      sensitivity among heparin-resistant patients undergoing CPB [292235,292861]. Full
      enrollment onto the US trial was complete by the end of first quarter 2000
      [363589], and the companies aim to complete trials and submit a filing by the end
      of 2000 [353372]. Clinical trials of the proteins in Japan were expected to begin
      in 1998 [286086].

PMID- 16096932
TI  - [Association between carotid atherosclerosis, inflammatory markers and Chlamydia
      pneumoniae infection].
AB  - BACKGROUND AND PURPOSE: The aim of this study was to assess the correlation
      between morphological markers of carotid atherosclerosis, such as intima-media
      thickness (IMT) and the cross-sectional plaque area with markers of inflammation
      and C. pneumoniae infection. MATERIAL AND METHODS: The study involved a group of
      128 persons (63 females, 49.2%), including 54 atherothrombotic stroke patients.
      The IMT and cross-sectional plaque area of common and internal carotid arteries
      were measured by ultrasonography. We assessed the C-reactive protein (CRP) and
      fibrinogen blood level, white blood cell (WBC) count, levels of IgA and IgG
      antibodies against C. pneumoniae , additionally the presence of C. pneumoniae DNA
      in WBCs was detected by PCR. We also considered the following risk factors:
      hypertension, diabetes, obesity and smoking. RESULTS: The multiple regression
      analysis showed the strongest and independent correlations of WBC with the IMT
      (r=0.32; p=0.0003) and plaque area (r=0.24; p=0.008) increase. Also other
      factors, such as smoking (r=0.19; p=0.026), hypertension (r=0.18; p=0.023) and
      CRP concentration (r=0.17; p=0.036) showed a significant correlation with carotid
      IMT. C. pneumoniae -specific IgG antibodies level showed a significant
      correlation with IMT only in the linear regression analysis, but not in the
      multiple regression analysis. C. pneumoniae DNA presence results did not reveal a
      significant correlation with either IMT or the carotid plaque area. CONCLUSION:
      Inflammatory markers, especially the WBC count and CRP level, showed an
      independent and stronger correlation with carotid atherosclerosis than markers of
      C. pneumoniae infection.

PMID- 16096933
TI  - [The role of computerized rheoencephalography in the assessment of normal
      pressure hydrocephalus. Preliminary report].
AB  - BACKGROUND AND PURPOSE: It is generally agreed that the positive result of lumbar
      cerebrospinal fluid (CSF) withdrawal offers a reliable means for selection of
      patients likely to respond to shunting in normal pressure hydrocephalus (NPH).
      However the studies of cerebral hemodynamics in NPH are performed Routinely only
      in few neurosurgical centers. We therefore studied the effect of CSF withdrawal
      on cerebrovascular autoregulation (CVA) in this condition by means of
      computerized rheoencephalography [REG]. MATERIAL AND METHODS: The study group
      consisted of 27 patients with presumed posttraumatic NPH. In each patient both
      the tap test and infusion test were performed. Psychometric tests and
      rheoencephalographic examinations were made twice: before and after CSF
      withdrawal. The obvious restoration of the functional state of CVA after CSF
      withdrawal was considered as a positive result of the tap test. RESULTS: Fourteen
      patients with a positive tap test and/or with resistance to CSF outflow (Rout) of
      more than 11 mmHg/ml/min were shunted. The improvement was obtained in 10 of
      them. Only one patient with a positive tap test did not improve. CONCLUSIONS: Our
      study suggests that restoration of CVA after CSF withdrawal is associated with
      high likelihood of shunt success, but not vice versa. Evaluation of CVA using REG
      seems to offer a new diagnostic tool in selecting patients likely to respond to
      shunting. Further studies are necessary to optimize the amount of CSF withdrawal,
      the delay between CSF withdrawal and control examinations and methodology of
      neuropsychological examinations.

PMID- 16096934
TI  - [Endoscopic revision of adherent ventricular catheter. Evaluation of the method].
AB  - BACKGROUND AND PURPOSE: To evaluate the method of endoscopic-assisted revision of
      adherent ventricular catheters. MATERIAL AND METHODS: 29 cases (26 patients) of
      endoscopic revision of adherent ventricular catheter were analyzed. The cause of
      hydrocephalus was intraventricular hemorrhage in 17 cases, myelomeningocele in 3
      cases, ventriculitis in 4 cases, aqueductal stenosis in 1 case and
      holoprosencephaly in 1 case. Multiloculated hydrocephalus comprised 38.5% (10
      patients) of cases. Depending on the catheter location, an approach through its
      burr hole, a new burr hole on the same side or opposite side was used. The mean
      time of follow up was 12 months. RESULTS: In 13 cases ventricular catheter was
      tethered in the choroid plexus, in 7 cases -- under the ependyma and in 9 cases -
      in septum pellucidum. In 5 cases it was adherent to the blood vessel. An entity
      of active ingrowth of choroid plexus, ependyma and subependymal elements into the
      catheter lumen was observed. Reocclusion of the catheter occurred in 3 cases. In
      all these cases there was multiloculated hydrocephalus. In the remaining cases
      there were no signs of shunt malfunction during the time of follow up.
      CONCLUSIONS: The use of endoscope during revision of adherent ventricular
      catheter reduces the risk of bleeding. Due to a possibility of direct observation
      of catheter surroundings, a decision regarding catheter replacement and its
      placement in an optimal position can be taken. This method gives better results
      than traditional methods used during revisions of occluded, adherent ventricular
      catheters.

PMID- 16096935
TI  - [Incidence of neuromedical complications during rehabilitation after stroke].
AB  - BACKGROUND AND PURPOSE: The aim of the study was to examine the frequency and
      types of neuromedical complications in stroke rehabilitation depending on the
      age, sex and time from the onset of stroke. MATERIAL: 498 patients after stroke
      (225 females, 227 males) during inpatient rehabilitation in the Rehabilitation
      Department at the Provincial Hospital no. 2 in Rzeszow. RESULTS: At least one
      complication after stroke was stated in 391 (78.5%) patients. We recorded the
      following neurological complications: recurrent stroke (2.8%), epileptic seizures
      (9.8%), depression (14.7%), confusion (10.6%) and medical complications: urinary
      tract infections (36.9%), pneumonia (9.8%), falls (11.8%), deep vein thrombosis
      (2%), pulmonary embolism (1.4%) and paretic limb problems (pain -- 23.1%, edema -
      20.9%, shoulder subluxation -- 3.2%). Females were more likely to have urinary
      tract infections and pulmonary embolism. Patients over 80 years suffered more
      frequently from multiple complications. Age turned out to be a risk factor for
      stroke progression, pulmonary embolism, gastrointestinal bleeding and confusion.
      The frequency of complications was related with duration after stroke. Urinary
      tract infections, pneumonias, mental disorders and falls were more common up to
      three months from the onset of stroke, while epileptic seizures occurred more
      frequently over three months after stroke. CONCLUSIONS: At least one medical
      complication is noted in most patients after stroke during their rehabilitation,
      careful prevention, early diagnostics and treatment of complications after stroke
      are necessary in order to make rehabilitation after stroke more effective.

PMID- 16096936
TI  - [Changes of protein S100B serum concentration during ischemic and hemorrhagic
      stroke in relation to the volume of stroke lesion].
AB  - BACKGROUND AND PURPOSE: Biochemical markers offer a new strategy in the
      diagnosis, estimation of clinical prognosis and monitoring of treatment in
      patients with brain damage. At present, two specific brain originated proteins
      play a major role: S100B protein and neuron-specific enolase (NSE). S100B comes
      from astrocytes and NSE has been found in neuronal cytoplasm. The aim of this
      study was to evaluate dynamics of protein S100B level changes in blood in stroke
      patients. MATERIAL AND METHODS: The material consisted of 67 patients, 53 with
      ischemic stroke (mean age 67.7) and 14 with hemorrhagic stroke (mean age 66.7).
      The diagnosis of stroke was made on the basis of clinical symptoms and computed
      tomography (CT). Plasma concentration of S100B was measured using the
      immunoluminometric test (Lia-Mat Sangtec 100(R)) on the 1st, 3rd, 7th and 14th
      day after stroke onset. RESULTS: The highest levels of protein S100B were found
      in ischemic stroke predominantly on the 3rd day and in hemorrhagic stroke on the
      1st day. The concentrations of protein S100B were similar in ischemic and
      hemorrhagic stroke on the 3rd, 7th and 14th day but they were significantly
      higher on the 1st day in hemorrhagic stroke. Serum levels of protein S100B after
      stroke onset have shown a correlation with infarct volume, especially in patients
      with large or medium stroke. In small stroke lesions, concentrations of protein
      S100B were under the cut-off level. In hemorrhagic stroke protein S100B levels
      were higher in patients with midline shift visible in brain CT, but the
      differences were not significant. CONCLUSIONS: Ischemic and hemorrhagic strokes
      lead to release of protein S100B into the blood. A good correlation between the
      release pattern of S100B and volume of vascular lesion has been found. S100B
      protein is the marker of brain damage during stroke. It is possible to use
      protein S100B measurements in monitoring the stroke treatment.

PMID- 16096937
TI  - [Will statins be used in dementia treatment?].
AB  - The paper presents current opinions on the mechanism of beta-amyloid
      accumulation, the role of cholesterol in the pathogenesis of dementia and
      observations of the role of statins in its development. Most of the observations
      were done on Alzheimer's disease, some of them concerned also dementia of a
      vascular origin and cognition. Statins are inhibitors of the cholesterol
      synthesis pathway. The mechanism of their action concerns not only their
      influence on the cholesterol level but also their influence on prenylation of
      various proteins and in consequence inhibition of inflammatory reactions. They
      exert also antioxidative activity. As the number of prospective studies is still
      insufficient the question whether statins could be used as drugs against dementia
      remains still unsolved.

PMID- 16096938
TI  - [Role of proteoglycans and glycosaminoglycans in the intervertebral disc
      degeneration].
AB  - Proteoglycans and glycosaminoglycans are the main components of the extracellular
      matrix of the nucleus pulposus. Intervertebral disc degeneration due to aging and
      excessive mechanical loads results in adverse quantitative and structural changes
      to the macromolecules. Metalloproteinases induced by inflammatory mediators play
      a key role in degrading proteoglycans. Progressive matrix breakdown decreases
      water content in the disc. Dehydration compromises disc cells function and
      impairs resistance to compression. Biochemical changes may result in disc
      prolapse. Modifying the metabolism of proteoglycans and glycosaminoglycans might
      be an effective therapeutic strategy.

PMID- 16096939
TI  - [Arachnoid cysts of the middle cranial fossa presented as subdural hematomas].
AB  - The aim of the study was to present the authors' own experience and discuss the
      treatment method of arachnoid cysts of the middle cranial fossa disclosed as
      subdural hematoma. Three cases of male patients operated on because of chronic
      subdural hematoma are presented. Control CT studies after evacuation of hematomas
      revealed arachnoid cysts of the middle cranial fossa and all patients were
      qualified for delayed cystocisternostomy by open craniotomy. Indirect signs of
      presence of arachnoid cysts in the form of bony abnormalities and expanded the
      middle cranial fossa in the first CT were seen in all patients. Cysts were
      asymptomatic until the injury in all cases. The volumes of cysts in MRI scans
      were: 17.8 ml, 52.9 ml and 92.4 ml, respectively. All cysts were type II
      according to Galassi classification. After control MRI described above made to
      evaluate cyst appearance, delayed cystocisternostomy to basal cisterns was
      undertaken in two cases with full success. No complications were observed. The
      third patient refused surgery. During surgery the thick and non-transparent
      medial cyst wall and arachnoidea of tentorial notch cisterns were observed
      impeding the exact identification of neurovascular structures. In our opinion
      arachnoid cysts of the middle cranial fossa revealed as subdural hematoma should
      be operated on in two stages: in the first step subdural hematoma should be
      evacuated and in the second step cystocisternostomy should be performed. With
      regard to observed morphological changes of arachnoidea and cyst walls we think
      that open cystocisternostomy is treatment of choice in these cases.

PMID- 16096940
TI  - [Melkersson-Rosenthal syndrome as a rare cause of recurrent facial nerve palsy].
AB  - Melkersson-Rosenthal syndrome is a rare cause of recurrent facial nerve palsy.
      The syndrome is classically characterized by a triad of signs consisting of
      facial edema, recurrent peripheral facial nerve paralysis, and congenital
      fissured tongue, although it may also present in a mono- or oligosymptomatic
      form. The paper presents a 24-year-old woman with right-sided peripheral facial
      nerve palsy and a history of left-sided episodes of facial nerve palsy. Magnetic
      resonance angiography of the cerebral vessels suggested compression of the right
      seventh and eighth cranial nerves by a vascular loop. The authors describe the
      patient with a complete picture of Melkersson-Rosenthal syndrome and discuss the
      diagnosing process and treatment.

PMID- 16096941
TI  - [Can non-steroidal anti-inflammatory drugs be improved?].

PMID- 16096942
TI  - [Spinocerebellar ataxias type 1 and 2: comparison of clinical,
      electrophysiological and magnetic resonance evaluation].
AB  - BACKGROUND AND PURPOSE: Spinocerebellar ataxias type 1 (SCA1) and type 2 (SCA2)
      belong to neurodegenerative disorders of autosomal dominant inheritance,
      genetically and clinically heterogeneous, caused by the expansion of CAG
      trinucleotides. Trunk and limb ataxia, dysarthria, dysphagia, gaze palsy, sensory
      and motor axonal neuropathy are the dominant features in both entities. The aim
      of the study was to evaluate the differences between genotype and phenotype based
      on clinical and electrophysiological assessment of the visual, auditory pathways,
      and EEG alterations in comparison with the cerebellar and brain atrophy in MRI.
      MATERIAL AND METHODS: 44 patients with SCA1 and 24 cases with SCA2 confirmed
      molecularly were examined neurologically and using the International Cooperative
      Ataxia Rating Scale (ICARS). A correlation of clinical symptoms and signs, and
      CAG repeat numbers with EEG, visual (VEP) and brainstem auditory (BAEP) evoked
      potentials, and MRI alterations were evaluated. RESULTS: A statistically
      significant negative correlation between the age of disease onset and number of
      CAG repeats in both types of SCA was found. Examined patients with SCA2 were
      younger, with longer disease duration and more pronounced cerebellar and brain
      atrophy in MRI. We found a significant correlation between ICARS and CAG repeats
      in this group. The dysphagia, pyramidal tract involvement and depressive reaction
      were significantly frequent in SCA1 patients. However in SCA2 patients, the
      peripheral nerve damage and extrapyramidal signs were more prominent. The
      amplitude of P100 visual evoked potentials was significantly lower in SCA1
      patients and negatively correlated with CAG repeats. CONCLUSIONS: These results
      provide further evidence for the phenotypic differences of genetically defined
      SCA1 and SCA2 patients, expressed by more frequent involvement of the pyramidal
      tract and depression reaction in SCA1, in contrast to peripheral nerve
      involvement and extrapyramidal signs in the clinical feature of SCA2 phenotype.
      Furthermore, atrophy of the brain and cerebellum revealed in MRI was more
      pronounced than electrophysiological functional alterations, especially in SCA2.
      The decreased amplitude of P100 VEP in SCA1 patients was the only
      electrophysiological parameter differentiating between both groups of patients.

PMID- 16096943
TI  - Free-flap monitoring using a chimeric sentinel muscle perforator flap.
AB  - Muscle perforator flaps have become an important resource for the creation of
      cutaneous flaps based on musculocutaneous perforators, but without inclusion of
      the involved muscle. As a chimeric flap with or without the muscle, the cutaneous
      perforator flap can specifically serve as a sentinel or monitoring flap to allow
      the early detection of anastomotic compromise involving the common source vessel,
      without the need for direct observation of the major free-flap component. This
      can be a valuable adjunctive use of muscle perforator flaps for the continuous
      assessment of free muscle flaps or as an exteriorized flap for the monitoring of
      buried free flaps.

PMID- 16096944
TI  - Salvage of a radial forearm flap transferred onto a by-pass graft with conversion
      from a high-to-low-resistance circulatory pattern: case report.
AB  - With a radial forearm flap, a flow-through flap can be designed to help decrease
      overall resistance, if an adequate distal arterial target is available. When this
      is not possible, creation of an arteriovenous fistula is an option to salvage a
      high-resistance flap transferred onto a high-flow arterial system.

PMID- 16096945
TI  - Successful replantation of the leg in a pre-ambulatory infant.
AB  - The authors report the first successful replantation of a below-knee amputation
      in a 7-month-old infant prior to the development of a standing and walking gait.
      Seven years following surgery, the child demonstrates excellent ankle and knee
      range of motion, has regained plantar sensation, and is able to walk, run, and
      jump without needing a brace. Despite a leg-length discrepancy of 5.5 cm, it is
      likely that future overgrowth of the injured limb will improve this discrepancy.
      This child has excellent potential for a successful functional outcome, given the
      very young age at the time of replantation and the plasticity of the central
      nervous system.

PMID- 16096946
TI  - Patient-reported donor-site morbidity following anterolateral thigh free flaps.
AB  - This study evaluated donor-site morbidity (retrospective chart review and
      followup questionnaire) in patients following reconstruction using an
      anterolateral thigh free flap. Twenty-one flaps were performed in 20 consecutive
      patients (mean age: 45.0 +/- 3.8 years). Primary wound closure was obtained in
      52.4 percent. The perforators were intramuscular in 68 percent and septocutaneous
      in 32 percent. The early complications included infection (n = 2), wound
      dehiscence (n = 2), delayed healing (n = 8), and seroma (n = 1). Wound healing
      took 4.5 +/- 0.7 weeks, and leg weakness resolved completely (n = 13) by 6.6 +/-
      2.0 weeks. More chronic complications (n = 19) included weakness (n = 5),
      pain/tightness (n = 6), contour deformity (n = 14), muscle herniation (n = 6),
      and unsatisfactory scar appearance (n = 6). No statistically significant
      differences existed in aesthetics or healing between wound-closure groups, nor in
      pain or weakness between perforator groups. Pain and weakness were significantly
      related to sacrifice of the deep fascia from the thigh through its elevation in
      the flap.

PMID- 16096947
TI  - Reconstruction of the form and function of lateral malleolus and ankle joint.
AB  - Soft-tissue reconstruction alone cannot obtain normal ankle function in patients
      with large defects in the area of the lateral malleolus. The authors report a
      functional reconstructive method for the lateral malleolus, utilized in a male
      patient whose osteosarcoma in the fibula was resected with surrounding soft
      tissue. In order to reconstruct the lateral malleolus, the remaining half of the
      fibula at the knee was removed, and the fibular head was fixed with the tibia at
      the ankle joint. Ligaments were reconstructed with tendon grafts. Skin and soft
      tissue defects were reconstructed with a combined composite flap comprised of a
      latissimus dorsi myocutaneous flap and a serratus anterior muscle flap. Dead
      space around the bone graft was filled with the serratus anterior muscle flap
      that was divided into two portions. The surface was covered with the latissimus
      dorsi myocutaneous flap. The patient regained almost normal function of the ankle
      joint. This technique would be a useful functional reconstructive method for
      patients with large defects in the area of the lateral malleolus.

PMID- 16096948
TI  - Simultaneous bilateral microvascular tissue transfer for soft-tissue defects of
      the lower extremities in pyoderma gangrenosum.
AB  - Pyoderma gangrenosum is a necrotizing skin disease of unknown etiology. The
      lesions are painful and occur mostly on the lower extremities, either single or
      multiple, but can appear in any region of the body. The authors report a case of
      pyoderma gangrenosum involving bilateral skin lesions over the anterior surface
      of the legs in a 13-year-old male patient. The lesions presented with ulcerative
      colitis, which is one of the most commonly associated diseases of pyoderma
      gangrenosum. After examination, systemic immunosuppressive treatment was
      administered and the progression of the disease was controlled. The lesions were
      treated with the simultaneous application of two free anterolateral thigh
      fasciocutaneous flaps after radical debridement. The procedure was successfully
      performed and no recurrence was observed. Although microvascular free tissue
      transfer cannot be performed in a standard fashion in pyoderma gangrenosum cases
      because of the risk of pathergy response, it should be considered as a surgical
      option in selected cases, otherwise difficult to manage, with the simultaneous
      application of appropriate systemic medical treatment.

PMID- 16096949
TI  - Early effect of gene therapy on a direct muscle neurotization model.
AB  - Direct nerve-to-muscle neurotization has been the subject of both clinical and
      experimental studies. In this study, the authors report a new animal model to
      test the regenerative properties of a nerve (musculocutaneous) implanted in a
      muscle (biceps). They also report the early effects of the application at the
      implantation site of exogenously administered Brain Derived Nerve Factor (BDNF)
      and of endogenously produced BDNF, via the administration of an adenoviral
      construct with a tissue-specific promotor for muscle cells (AdRSV), and
      containing the BDNF gene. Evaluation included behavioral testing (grooming test),
      electrical stimulation, Western blot analysis of the distal implanted nerve to
      determine the presence of locally produced BDNF, and motor end-plate staining of
      the biceps muscle. At the early time point of 1 week following the
      musculocutaneous nerve to biceps muscle implantation, there was no increased
      production of recombinant BDNF at the distal implanted musculocutaneous nerve, as
      assessed by Western blot analysis. Therefore, there was no significant difference
      in the behavioral evaluation of the animals at 1 week; the Terzis grooming test
      showed no statistical difference among groups, but a trend toward better function
      for the BDNF and the high-dose AdRSV-BDNF groups, compared to the control groups.
      There was also no difference in the histologic appearance and number of the motor
      end-plates at the implantation site, compared to the controls. The electrical
      stimulation of the MC nerve did not produce statistically significant results
      among the experimental groups. In this direct nerve to muscle neurotization
      model, the application of AdRSV-BDNF at 3 x 10 (9) pfu/ul did not show enhanced
      production of BDNF at 1 week.

PMID- 16096950
TI  - Vascular endothelial growth factor gene therapy in improvement of skin paddle
      survival in a rat TRAM flap model.
AB  - The use of growth factors in inducing angiogenesis and enhancing flap viability
      has provided promising results. Targeted gene therapy has evolved in hopes of
      increasing the longevity and effectiveness of these growth factor treatments. The
      purpose of this study was to examine the effect of preoperative treatment by
      vascular endothelial growth factor (VEGF) plasmid DNA on the survival of the skin
      paddle in a rat pedicled TRAM flap model. In part one of the study, VEGF plasmid
      DNA incorporated with lipofectamine was injected into the subcutaneous fascial
      layer of the upper abdominal walls of the rats. At 4 days postoperatively,
      biopsies were taken from the injected area for histology and VEGF protein
      quantification. In part two of the study, the rats were divided into three
      groups. In one experimental group, the VEGF plasmid DNA was injected into the
      subcutaneous fascial layer in the area where the TRAM flap would be elevated. In
      two control groups, the plasmid without VEGF DNA and saline were injected. The
      flaps were raised and replaced 4 days after injection. Flap survival was
      examined. Results showed that tissue receiving VEGF plasmid DNA injection
      revealed new vessel sprouting. The VEGF levels in these tissues were
      significantly higher than in the tissue not receiving VEGF plasmid DNA. In flap
      survival, the mean viable area of the skin paddles receiving preoperative VEGF
      plasmid DNA injection was significantly larger than that of flaps receiving no
      VEGF plasmid DNA and saline injection. This study demonstrated that preoperative
      subcutaneous injection of VEGF plasmid DNA could induce angiogenesis and improve
      TRAM skin paddle survival.

PMID- 16096951
TI  - Effects of irradiation on nerve graft vasculature.
AB  - Increasing doses of therapeutic irradiation are known to impair nerve
      regeneration after grafting. One possible factor is the effect of irradiation on
      the endoneurial vasculature. This study investigates the effects of postoperative
      irradiation on the size, number, and cross-sectional area of endoneurial vessels
      in the rat posterior tibial nerve graft model. Sixty-five Sprague-Dawley rats
      underwent 1.5-cm interposition grafts to the tibial nerve. Postoperatively, they
      were assigned to one of five groups. The animals in Group 1 were unirradiated
      controls. Groups 2 to 5 received postoperative irradiation in the amounts of 46,
      66, 86, and 106 Gy, respectively. One hundred and twenty days after grafting,
      sections of the proximal, grafted, and distal nerve were harvested and analyzed
      with digital morphometry. Statistical analysis of the average vessel area, number
      of vessels, and total vascular area was performed. The grafted segments of Groups
      4 and 5 and the distal segments of all irradiated groups showed a statistically
      significant decrease in the number of vessels, compared to controls. The average
      size of the vessel was smaller in the proximal segment of the irradiated groups,
      compared to controls. There was no difference in size in either the grafted or
      distal segments of the irradiated groups, compared to controls. The observed
      changes in the endoneurial vasculature resulted from both the action of
      regeneration and the effects of irradiation. The irradiation effects appear to be
      dose-dependent.

PMID- 16096952
TI  - On "use of soleus muscle flaps for coverage of distal third tibial defects" (J
      Reconstr Microsurg 2004;20:593-597).

PMID- 16096954
TI  - Abstracts of the American Society for Reconstructive Microsurgery (ASRM) annual
      meeting. Fajardo, Puerto Rico, January 15-18, 2005.

PMID- 16096956
TI  - Historical perspectives on plant developmental biology.
AB  - The early studies of plant growth and development focused on embryogenesis. In
      the past twenty five years, it became possible to successfully analyze many more
      developmental processes, hence plant developmental biology became the generally
      accepted terminology. It refers to a multidisciplinary approach using expertise
      and tools from genetics, molecular biology and cell biology to study processes in
      development also beyond the formation of the embryo. Around that time,
      initiatives were taken to address biological questions in just a few model
      systems, such as Arabidopsis thaliana, Zea mays, Antirrhinum majus and Petunia
      hybrida, while the <<old>> model systems, i.e. potato, tobacco, used in
      regeneration and grafting experiments, were increasingly abandoned. International
      research programs were initiated in Arabidopsis at first to create stock centers
      and databases to proceed faster with the scientific research and to get deeper
      insight into plant biology. During the last five years the maize community made
      tremendous progress in developing tools and resources for their system.
      Milestones in plant developmental biology discussed relate to the molecular
      genetic approach to study embryogenesis, autoregulation of meristems, leaf and
      flower initiation, leaf and flower formation and cell specification in the root.
      Developmental biology changed the research from descriptive to causal resulting
      in a number of genetic models. Future developments in research will focus on the
      study of a specific gene activity in a genome-wide context. The building of
      molecular networks will allow computer modeling of biological processes and its
      use for predictions and further experimentation. Sequence information derived
      from the multiple genome projects will be exploited in comparative biology.

PMID- 16096957
TI  - Balance between cell division and differentiation during plant development.
AB  - The processes which make possible that a cell gives rise to two daughter cells
      define the cell division cycle. In individual cells, this is strictly controlled
      both in time and space. In multicellular organisms extra layers of regulation
      impinge on the balance between cell proliferation and cell differentiation within
      particular ontogenic programs. In contrast to animals, organogenesis in plants is
      a post-embryonic process that requires developmentally programmed reversion of
      sets of cells from different differentiated states to a pluripotent state
      followed by regulated proliferation and progression through distinct
      differentiation patterns. This implies a fine coupling of cell division control,
      cell cycle arrest and reactivation, endoreplication and differentiation. The
      emerging view is that cell cycle regulators, in addition to controlling cell
      division, also function as targets for maintaining cell homeostasis during
      development. The mechanisms and cross talk among different cell cycle regulatory
      pathways are discussed here in the context of a developing plant.

PMID- 16096958
TI  - Plant stem cell niches.
AB  - Stem cells are required to support the indeterminate growth style of plants.
      Meristems are a plants stem cell niches that foster stem cell survival and the
      production of descendants destined for differentiation. In shoot meristems, stem
      cell fate is decided at the populational level. The size of the stem cell domain
      at the meristem tip depends on signals that are exchanged with cells of the
      organizing centre underneath. In root meristems, individual stem cells are
      controlled by direct interaction with cells of the quiescent centre that lie in
      the immediate neighbourhood. Analysis of the interactions and signaling processes
      in the stem cell niches has delivered some insights into the molecules that are
      involved and revealed that the two major niches for plant stem cells are more
      similar than anticipated.

PMID- 16096959
TI  - Circadian clock signaling in Arabidopsis thaliana: from gene expression to
      physiology and development.
AB  - The daily rotation of the earth on its axis leads to predictable periodic
      fluctuations of environmental conditions. Accordingly, most organisms have
      evolved an internal timing mechanism, the circadian clock, which is able to
      recognize these 24-hour rhythmic oscillations. In plants, the temporal
      synchronization of physiology with the environment is essential for successful
      plant growth and development. The intimate connection between light signaling
      pathways and the circadian oscillator allows the anticipation of the
      environmental transitions and the measurement of day-length as an indicator of
      changing seasons. In recent years, significant advances have been made in the
      genetic and molecular dissection of the plant circadian system, mostly in
      Arabidopsis thaliana. The overall plant clock organization is highly complex; the
      system seems to include several input pathways, tightly regulated central
      oscillators and a myriad of outputs. The molecular cloning and characterization
      of a number of clock components has greatly improved our view of the plant
      central oscillator and additional players will most likely come into place very
      soon. Molecular mechanisms underlying circadian clock function are also beginning
      to be characterized. The emerging model relies on negative feedback loops at the
      core of the oscillator. Additional levels of post-transcriptional and post
      translational regulation also contribute to the generation and maintenance of the
      rhythms. Globally, these studies have shed new light on how the clock coordinates
      plant physiology and development with the daily and seasonal environmental
      cycles.

PMID- 16096960
TI  - Regulation of gene expression by light.
AB  - Light signals perceived mainly by phytochromes and cryptochromes regulate plant
      growth and development by driving dramatic shifts of the transcriptome. Early
      light-responsive genes include a large proportion of transcripton factors of
      different DNA binding motifs. Mutations at loci encoding several transcriptional
      regulators, including some of those showing rapid changes in transcript levels,
      impair responses to light in Arabidopsis thaliana. Proteasome-mediated
      degradation involving the E3 ligase COP1 provides an additional layer of control
      of the levels of transcription factors. Some transcriptional regulators are
      shared by light, circadian and/or hormonal signalling circuits creating complex
      networks that interactively integrate environmental and endogenous cues.

PMID- 16096961
TI  - Genetic control of floral size and proportions.
AB  - Floral size is an ecologically important trait related to pollination success and
      genetic fitness. Independently of the sexual reproduction strategy, in many
      plants, floral size seems to be controlled by several genetic programs that are
      to some extent independent of vegetative growth. Flower size seems to be governed
      by at least two independent mechanisms, one controlling floral architecture that
      affects organ number and a second one controlling floral organ size. Different
      organ-dependent growth control may account for the final proportions of a flower
      as a whole. Genes controlling floral organ identity, floral symmetry and organ
      polarity as well as auxin and gibberellin response, also play a role in
      establishing the final size and architecture of the flower. The final size of an
      organ seems to be controlled by a systemic signal that might in some cases
      overcome transgenic modifications of cell division and expansion. Nevertheless,
      modification of basic processes like cell wall deposition might produce important
      changes in the floral organs. The coordination of the direction of cell division
      and expansion by unknown mechanisms poses a challenge for future research.

PMID- 16096962
TI  - Flower symmetry and shape in Antirrhinum.
AB  - According to their symmetry, flowers are classified as radially symmetrical or
      bilaterally symmetrical. Bilateral symmetry, which is thought to have evolved
      from radial symmetry, results from establishment of asymmetry relative to a
      dorsoventral axis of flowers. Here we consider developmental genetic mechanisms
      underlying the generation of this asymmetry and how they relate to controls of
      petal shape and growth in Antirrhinum. Two genes, CYC and DICH, are expressed in
      dorsal domains of the Antirrhinum flower and determine its overall dorsoventral
      asymmetry and the asymmetries and shapes of individual floral organs, by
      influencing regional growth. Another gene, DIV, influences regional asymmetries
      and shapes in ventral regions of the flower through a quantitative effect on
      growth. However, DIV is not involved in determining the overall dorsoventral
      asymmetry of the flower and its effects on regional asymmetries depend on
      interactions with CYC/DICH. These interactions illustrate how gene activity,
      symmetry, shape and growth may be related.

PMID- 16096963
TI  - Regulation of phyllotaxis.
AB  - Plant architecture is characterized by a high degree of regularity. Leaves,
      flowers and floral organs are arranged in regular patterns, a phenomenon referred
      to as phyllotaxis. Regular phyllotaxis is found in virtually all higher plants,
      from mosses, over ferns, to gymnosperms and angiosperms. Due to its remarkable
      precision, its beauty and its accessibility, phyllotaxis has for centuries been
      the object of admiration and scientific examination. There have been numerous
      hypotheses to explain the nature of the mechanistic principle behind phyllotaxis,
      however, not all of them have been amenable to experimental examination. This is
      due mainly to the delicacy and small size of the shoot apical meristem, where
      plant organs are formed and the phyllotactic patterns are laid down. Recently,
      the combination of genetics, molecular tools and micromanipulation has resulted
      in the identification of auxin as a central player in organ formation and
      positioning. This paper discusses some aspects of phyllotactic patterns found in
      nature and summarizes our current understanding of the regulatory mechanism
      behind phyllotaxis.

PMID- 16096964
TI  - Leaf shape: genetic controls and environmental factors.
AB  - In recent years, many genes have been identified that are involved in the
      developmental processes of leaf morphogenesis. Here, I review the mechanisms of
      leaf shape control in a model plant, Arabidopsis thaliana, focusing on genes that
      fulfill special roles in leaf development. The lateral, two-dimensional expansion
      of leaf blades is highly dependent on the determination of the dorsoventrality of
      the primordia, a defining characteristic of leaves. Having a determinate fate is
      also a characteristic feature of leaves and is controlled by many factors.
      Lateral expansion is not only controlled by general regulators of cell cycling,
      but also by the multi-level regulation of meristematic activities, e.g., specific
      control of cell proliferation in the leaf-length direction, in leaf margins and
      in parenchymatous cells. In collaboration with the polarized control of leaf cell
      elongation, these redundant and specialized regulating systems for cell cycling
      in leaf lamina may realize the elegantly smooth, flat structure of leaves. The
      unified, flat shape of leaves is also dependent on the fine integration of cell
      proliferation and cell enlargement. Interestingly, while a decrease in the number
      of cells in leaf primordia can trigger a cell volume increase, an increase in the
      number of cells does not trigger a cell volume decrease. This phenomenon is
      termed compensation and suggests the existence of some systems for integration
      between cell cycling and cell enlargement in leaf primordia via cell-cell
      communication. The environmental adjustment of leaf expansion to light conditions
      and gravity is also summarized.

PMID- 16096965
TI  - Plastids unleashed: their development and their integration in plant development.
AB  - Derived by endosymbiosis from ancestral cyanobacteria, chloroplasts integrated
      seamlessly into the biology of their host cell. That integration involved a
      massive transfer of genes to the cell's nucleus, with the modification of pre
      existing processes, like plastid division and the operation of the plastid
      genetic machinery and the emergence of new ones, like the import of proteins
      translated in the cytoplasm. The uncovering in molecular detail of several of
      these processes reveals a merger of mechanisms of symbiont and host origin.
      Chloroplasts acquired roles as part of the biology of land plants by
      differentiating into a variety of interconvertible plastid forms according to the
      cell type. How these conversions take place, or how new problems, like the
      regulation of the plastid population size in cells, have been solved, is barely
      starting to be understood. Like the whole plant and as a result of the
      requirements and dangers associated with photosynthetic activity, chloroplasts in
      particular are under the control of environmental cues. Far from being passive
      targets of cellular processes, plastids are sources of signals of plastid-nuclear
      communication, which regulate activities for their own biogenesis. Plastids are
      also sources of developmental signals, in whose absence tissue architecture or
      cell differentiation are aberrant, in a cell-autonomous fashion. Over
      evolutionary time, plastids also contributed many genes for activities that are
      no longer directly associated with them (like light perception or hormone
      function). The overall picture is one in which plastids are at both the receiving
      and the acting ends in plant development, in both ontogenic and evolutionary
      terms.

PMID- 16096966
TI  - Epidermal differentiation: trichomes in Arabidopsis as a model system.
AB  - Arabidopsis trichomes are an excellent model system to study all aspects of cell
      differentiation including cell fate determination, cell cycle regulation, cell
      polarity and cell expansion. Genetic analysis had initially identified mutants
      affecting trichome development at different developmental stages. During recent
      years, molecular analysis of the corresponding genes has revealed a first glimpse
      of the underlying molecular mechanisms. This paper summarizes some of the recent
      insights regarding the mechanisms of trichome development.

PMID- 16096967
TI  - Flowering: a time for integration.
AB  - Flowering time is under the control of multiple environmental cues such as
      photoperiod and exposure to cold temperatures (vernalization). A few regulators
      named integrators of flowering time signals (LEAFY, SOC1 /AGL20 and FT )
      integrate inputs from the different flowering cascades and convey the resulting
      outcome to floral meristem identity genes at the shoot apex. Here we review the
      current knowledge about the expression of integrators, their mode of action,
      their potential target genes and the nature of their mutual interactions. We
      emphasize the questions that have been generated by recent progress in this field
      and that remain to be addressed.

PMID- 16096968
TI  - The making of gametes in higher plants.
AB  - Higher plants have evolved to be one of the predominant life forms on this
      planet. A great deal of this evolutionary success relies in a very short
      gametophytic phase which underlies the sexual reproduction cycle. Sexual plant
      reproduction takes place in special organs of the flower. In most species the
      processes of gametogenesis, pollination, syngamy and embryogenesis are
      sequentially coordinated to give rise to a functional seed in a matter of few
      weeks. Any of these processes is so intricately complex and precisely regulated
      that it becomes no wonder that each involves more specific genes and cellular
      processes than any other function in the plant life cycle. While variability
      generation - the evolutionary output of the sexual cycle - is the same as in any
      other Kingdom, plants do it using a completely original set of mechanisms, many
      of which are not yet comprehended. In this paper, we cover the fundamental
      features of male and female gametogenesis. While the physiological and cellular
      bases of these processes have been continuously described since the early
      nineteen century, recent usage of Arabidopsis and other species as central models
      has brought about a great deal of specific information regarding their genetic
      regulation. Transcriptomics has recently enlarged the repertoire and pollen
      became the first gametophyte to have a fully described transcriptome in plants.
      We thus place special emphasis on the way this newly accumulated genetic and
      transcriptional information impacts our current understanding of the mechanisms
      of gametogenesis.

PMID- 16096969
TI  - Gametophyte interaction and sexual reproduction: how plants make a zygote.
AB  - The evolutionary success of higher plants relies on a very short gametophytic
      phase, which underlies the sexual reproduction cycle. Sexual plant reproduction
      takes place in special organs of the flower: pollen, the male gametophyte, is
      released from the anthers and then adheres, grows and interacts along various
      tissues of the female organs, collectively known as the pistil. Finally, it
      fertilizes the female gametophyte, the embryo sac. Pollen is released as bi or
      tricellular, highly de-hydrated and presumably containing all the biochemical
      components and transcripts to germinate. Upon hydration on the female tissues, it
      develops a cytoplasmic extension, the pollen tube, which is one of the fastest
      growing cells in nature. Pollen is completely "ready-to-go", but despite this
      seemingly simple reaction, very complex interactions take place with the female
      tissues. In higher animals, genetic mechanisms for sex determination establish
      striking developmental differences between males and females. In contrast, most
      higher plant species develop both male and female structures within the same
      flower, allowing self-fertilization. Outcrossing is ensured by self
      incompatibility mechanisms, which evolved under precise genetic control,
      controlling self-recognition and cell-to-cell interaction. Equally important is
      pollen selection along the female tissues, where interactions between different
      cell types with inherent signalling properties correspond to check-points to
      ensure fertilization. Last but not least, pollen-pistil interaction occurs in a
      way that enables the correct targeting of the pollen tubes to the receptive
      ovules. In this review, we cover the basic mechanisms underlying sexual plant
      reproduction, from the structural and cellular determinants, to the most recent
      genetic advances.

PMID- 16096970
TI  - Flower and fruit development in Arabidopsis thaliana.
AB  - The study of flower development has experienced great advances over the last 15
      years. The most important landmark was the proposal of the ABC model in which
      three different functions of overlapping activities account for the development
      of the four rings of organs of the eudicot flower. Most interestingly, during
      recent years this simple and elegant model has been broadly accepted and is
      applicable to a wide range of plant species. However, recent advances in the
      characterization of protein interactions and the discovery of the SEPALLATA genes
      that are required for proper floral organ development have led to a revision of
      the ABC model. The largely accepted floral quartet model, which includes the new
      SEPALLATA function, postulates that the development of a specific floral organ is
      achieved by the formation of a single complex of different MADS-box proteins. The
      ultimate fate of the flower is to become a fruit, ensuring dispersal of the seeds
      and therefore survival of the species. The Arabidopsis fruit is a silique or pod.
      Only in the last five years important advances have been made in establishing the
      differentiation of the tissues required for the opening of the fruit: the valve
      margins and dehiscence zone. Classical genetic analyses and molecular biology
      approaches have pointed to the involvement of the transcription factors SHP, ALC
      and IND in the formation of these tissues and of FUL and RPL in repressing this
      identity in the bordering tissues, valves and replum, respectively.

PMID- 16096971
TI  - Seed maturation: developing an intrusive phase to accomplish a quiescent state.
AB  - Plants, as sessile life forms, have evolved diverse mechanisms to circumvent
      unfavourable growth conditions, among them interruption of the life cycle is one
      of the most successful strategies. During seed formation, embryo development can
      proceed through a maturation phase that allows the entry into a quiescent state
      and represents an evolutionary advantage, since it facilitates dispersal and
      resuming of growth under optimal environmental conditions. In the maturation
      phase different gene expression programmes devoted to the accumulation of storage
      compounds, acquisition of desiccation tolerance and entry into quiescence occur,
      which are highly coordinated and under fine regulatory control. This paper is
      focused on recent findings related to central transcription factors which
      regulate gene expression during maturation. The structure of established
      regulatory networks is presented based on extensive gene promoter analyses and
      the characterisation of mutants affecting seed development and maturation.
      Different aspects of gene regulation both in the embryo and endosperm are covered
      and comparisons between monocot and dicot species on the basis of current
      knowledge of the system are also presented.

PMID- 16096972
TI  - The signal transducing photoreceptors of plants.
AB  - Light signals are amongst the most important environmental cues regulating plant
      development. In addition to light quantity, plants measure the quality, direction
      and periodicity of incident light and use the information to optimise growth and
      development to the prevailing environmental conditions. Red and far-red
      wavelengths are perceived by the photoreversible phytochrome family of
      photoreceptors, whilst the detection of blue and ultraviolet (UV)-A wavelengths
      is conferred by the cryptochromes and phototropins. Higher plants contain
      multiple discrete phytochromes, the apoproteins of which are encoded by a small
      divergent gene family. In Arabidopsis, two cryptochrome and two phototropin
      family members have been identified and characterized. Photoreceptor action
      regulates development throughout the lifecycle of plants, from seed germination
      through to architecture of the mature plant and the onset of reproduction. The
      roles of individual photoreceptors in mediating plant development have, however,
      often been confounded by redundant, synergistic and in some cases mutually
      antagonistic mechanisms of action. The isolation of mutants null for individual
      photoreceptors and the construction of mutants null for multiple photoreceptors
      have therefore been paramount in elucidating photoreceptor functions.
      Photoreceptor action does not, however, operate in isolation from other
      signalling systems. The integration of light signals with other environmental
      cues enables plants to adapt their physiology to changing seasonal environments.
      This paper summarises current understanding of photoreceptor families and their
      functions throughout the lifecycle of plants. The integration of light signals
      with other environmental stimuli is also discussed.

PMID- 16096973
TI  - Plant tropisms: providing the power of movement to a sessile organism.
AB  - In an attempt to compensate for their sessile nature, plants have developed
      growth responses to deal with the copious and rapid changes in their environment.
      These responses are known as tropisms and they are marked by a directional growth
      response that is the result of differential cellular growth and development in
      response to an external stimulation such as light, gravity or touch. While the
      mechanics of tropic growth and subsequent development have been the topic of
      debate for more than a hundred years, only recently have researchers been able to
      make strides in understanding how plants perceive and respond to tropic
      stimulations, thanks in large part to mutant analysis and recent advances in
      genomics. This paper focuses on the recent advances in four of the best
      understood tropic responses and how each affects plant growth and development:
      phototropism, gravitropism, thigmotropism and hydrotropism. While progress has
      been made in deciphering the events between tropic stimulation signal perception
      and each characteristic growth response, there are many areas that remain
      unclear, some of which will be discussed herein. As has become evident, each
      tropic response pathway exhibits distinguishing characteristics. However, these
      pathways of tropic perception and response also have overlapping components - a
      fact that is certainly related to the necessity for pathway integration given the
      ever-changing environment that surrounds every plant.

PMID- 16096974
TI  - The highs and lows of plant life: temperature and light interactions in
      development.
AB  - Plants must constantly respond to changes in the environment whilst maintaining
      developmental and growth processes if they are to survive into the next
      generation. A complex network of signals from temperature and light must
      correctly converge to achieve successful development, through vegetative to
      reproductive growth. Temperature can be thought of as an environmental factor
      that provides both 'inductive' and 'maintenance' signals in development. It can
      stimulate developmental processes such as seed dormancy release, germination and
      vernalization. However, when temperature is not regarded as inductive, an
      accommodating network of genes work in concert to ensure growth responses occur
      regardless of fluctuating microclimate conditions. Many of the temperature
      regulated developmental pathways are intimately linked with light signaling. For
      example, light-temperature interactions are major determinants in the timing of
      reproductive development. Indeed, the ability to process and react to complex
      environmental cues is crucial for both normal and adaptive development in a
      changing environment. These responses are frequently mediated by manipulating the
      phytohormone network, which serves as a powerful, yet adaptable controller of
      development. This paper illustrates the influential role temperature perception
      plays throughout plant development and the close interaction between temperature,
      light and hormone signaling.

PMID- 16096975
TI  - Environmental regulation of flowering.
AB  - The timing of flower initiation is a highly plastic developmental process. To
      achieve reproductive success, plants must select the most favourable season to
      initiate reproductive development; this in turn requires continuous monitoring of
      environmental factors and a properly response. Environmental factors which change
      in a predictable fashion along the year, such as light and temperature, are the
      most relevant in terms of selection of the flowering season. In Arabidopsis and
      more recently in a few other species, molecular genetic analyses are providing a
      way to identify the genes involved in the regulation of flowering time. From gene
      sequences it is possible to develop hypotheses regarding molecular function and
      to infer some of the molecular mechanisms involved in the environmental
      regulation of flowering time. In this paper, we summarize recent discoveries
      concerning the mechanisms which plants use to perceive and respond to major
      environmental factors (light and temperature) and their different components. We
      focus mainly on annual plants and especially on Arabidopsis because most of the
      available molecular and functional data come from this species. However,
      additional information arising from other plant systems is also considered.

PMID- 16096976
TI  - Control of reproduction by Polycomb Group complexes in animals and plants.
AB  - In both mammals and plants, Polycomb Repressive Complexes 2 (PRC2) are conserved
      and appear to be involved in the transition between vegetative or somatic and
      reproductive state in plants and mammals. In plants at least three different PRC2
      control temporal aspects of development, and mutations in PcG cause
      heterochronies. Such heterochronic mutations affect the transition to flowering.
      During gametogenesis the Fertilization-Independent Endosperm-MEDEA-PRC2 (FIE-MEA
      PRC2) complex controls gametogenesis in synergy with a Retinoblastoma-dependent
      pathway. Several genes of the FIE-MEA pathway are imprinted as shown by their
      uniparental allele expression in the endosperm, the interface controlling
      maternal nutrition of the embryo in the seed. Imprinting is also a major feature
      for genes expressed in the placenta in mammals. Recent data have shown that
      imprinting in both placenta and endosperm likely share similar mechanisms
      involving cooperation between the PRC2 complexes and DNA methylation.

PMID- 16096977
TI  - From phenotypic to molecular polymorphisms involved in naturally occurring
      variation of plant development.
AB  - An enormous amount of naturally occurring genetic variation affecting development
      is found within wild and domesticated plant species. This diversity is presumably
      involved in plant adaptation to different natural environments or in human
      preferences. In addition, such intraspecific variation provides the basis for the
      evolution of plant development at larger evolutionary scales. Natural phenotypic
      differences are now amenable to genetic dissection up to the identification of
      causal DNA polymorphisms. Here we describe 30 genes and their functional
      nucleotide polymorphisms currently found as underlying allelic variation
      accounting for plant intraspecific developmental diversity. These studies provide
      molecular and cellular mechanisms that determine natural variation for
      quantitative and qualitative traits such as: fruit and seed morphology, colour
      and composition; flowering time; seedling emergence; plant architecture and
      inflorescence or flower morphology. Besides, analyses of flowering time variation
      within several distant species allow molecular comparisons between species, which
      are detecting homologous genes with partly different functions and unrelated
      genes with analogous functions. Thus, considerable gene function differences are
      being revealed also among species. Inspection of a catalogue of intraspecific
      nucleotide functional polymorphisms shows that transcriptional regulators are the
      main class of genes involved. Furthermore, barely more than half of the
      polymorphisms described are located in coding regions and affect protein
      structure, while the rest are regulatory changes altering gene expression. These
      limited analyses of intraspecific developmental variation support Doebley and
      Lukens's proposition (1998) that modifications in cis -regulatory regions of
      transcriptional regulators represent a predominant mode for the evolution of
      novel forms, but await more detailed studies in wild plant species.

PMID- 16096978
TI  - Plant microRNAs and development.
AB  - MicroRNAs (miRNAs) act as negative regulators of gene expression in eukaryotes, a
      discovery that has opened an expanding field of biological research. Plant miRNAs
      are known to repress gene expression posttranscriptionally, mainly by guiding
      cleavage but also by attenuating the translation of target transcripts. In
      addition, it has been shown that plant miRNAs can also act at the transcriptional
      level by directing the methylation of target chromosomal loci. Genetic and
      biochemical approaches are quickly broadening our knowledge of the biogenesis and
      function of plant miRNAs. Computational approaches have uncovered an unexpectedly
      large number of miRNAs and their targets in plants. The targets of plant miRNAs
      often belong to families of transcription factors involved in the control of
      developmental processes. We review the status of research in this dynamic field,
      summarizing recent advances in our understanding of the biogenesis and mechanism
      of action of plant miRNAs, as well as in the developmental processes they
      regulate.

PMID- 16096979
TI  - Gene network analysis in plant development by genomic technologies.
AB  - The analysis of the gene regulatory networks underlying development is of central
      importance for a better understanding of the mechanisms that control the
      formation of the different cell-types, tissues or organs of an organism. The
      recent invention of genomic technologies has opened the possibility of studying
      these networks at a global level. In this paper, we summarize some of the recent
      advances that have been made in the understanding of plant development by the
      application of genomic technologies. We focus on a few specific processes, namely
      flower and root development and the control of the cell cycle, but we also
      highlight landmark studies in other areas that opened new avenues of
      experimentation or analysis. We describe the methods and the strategies that are
      currently used for the analysis of plant development by genomic technologies, as
      well as some of the problems and limitations that hamper their application. Since
      many genomic technologies and concepts were first developed and tested in
      organisms other than plants, we make reference to work in non-plant species and
      compare the current state of network analysis in plants to that in other
      multicellular organisms.

PMID- 16096980
TI  - Long-range signalling in plant reproductive development.
AB  - Animals and plants produce regulatory signals at specific places of their bodies,
      in order to regulate developmental events which take place at a distance. Plants
      use this mechanism to adjust their development to the changing environment.
      Flowering and tuber formation are controlled by signals generated in the leaves
      that travel throughout the plant to reach their target tissues: the shoot apical
      meristem for flowering and the underground stolons for tuberization. Although the
      existence of these long-distance plant messengers was postulated almost seventy
      years ago, their chemical nature is still not clear. These leaf-derived signals
      are graft-transmissible and move through the plant vascular system. Presumably
      they are very similar or even identical for flowering and tuberization and common
      to most plant species. It is generally accepted that their composition is complex
      and includes positive and negative regulators. Many different substances,
      including classical plant hormones and metabolites have been postulated to be
      components of these mobile signals, but conclusive evidence of this is still
      lacking. Recent work has positioned these signals within the genetic network that
      regulates flowering time and suggests roles for specific genes in the generation,
      transport or response to the signalling molecules. Current knowledge of long
      range signalling mechanisms in other physiological and developmental events,
      together with the finding of common regulators involved in flowering,
      tuberization and other processes like pathogen and wound responses, should help
      to establish the biochemical composition of these elusive messenger signals.

PMID- 16096981
TI  - Regulated RNA processing in the control of Arabidopsis flowering.
AB  - Flowering time is controlled in order to ensure reproductive success. Molecular
      genetic analyses in Arabidopsis thaliana have identified many genes regulating
      this developmental switch. One group of factors which promote flowering do so by
      down-regulating the expression of the MADS-box floral repressor, FLC. RNA
      processing appears to play an important role in this regulation as genes within
      this group encode RNA binding proteins (FCA, FPA and FLK) and an mRNA 3' end
      processing factor (FY). FCA promotes flowering and negatively autoregulates its
      own expression post-transcriptionally through a mechanism that involves
      alternative polyadenylation. FCA physically interacts with FY and this
      interaction is required for the function FY performs in flowering control and in
      FCA autoregulation. Potential similarities are emerging in the molecular
      mechanisms controlling FLC expression and those controlling the floral homeotic
      gene, AGAMOUS. In addition, microRNAs have been shown to regulate plant
      developmental processes including the timing to flower. Together, these new data
      indicate that post-transcriptional regulation of gene expression plays an
      important role in regulating the floral transition.

PMID- 16096983
TI  - Living at the physiological limits: field and maximum metabolic rates of the
      common shrew (Sorex araneus).
AB  - Shrews (genus Sorex, small insectivorous mammals) are well known for their
      extremely high basal metabolic rates (BMRs) even when corrected for their small
      body size. We measured energy expenditure of the common shrew (Sorex araneus)
      under natural conditions (field metabolic rate [FMR]) by doubly labeled water
      method to test whether FMR is proportional to high BMR in this species. The study
      was performed in summer in northeastern Poland. In addition to the FMR, we also
      measured maximum metabolic rates induced by cold exposure and by intense activity
      (MMRCOLD and MMRRUN, respectively) to evaluate the aerobic reserve (MMR-FMR) in
      S. araneus. This aerobic reserve was used as an indicator of the potential for
      metabolic constraints. The FMR averaged 2.31+/-0.32 L CO2 d(-1) (+/-SD) or 58.1+/
      8.0 kJ d(-1) in 8.2-g animals. This figure constituted 216%-258% of a value
      predicted for a "standard" mammal of the same body mass and was the highest mass
      specific field metabolic rate in mammals. Because of the high BMR level in S.
      araneus, the FMR to BMR ratio (2.4) was not far off mammalian standards (median
      value of 3.1). The rate of water efflux determined in S. araneus (20.2 mL H2O d(
      1) or 2.46 mL H2O g(-1) d(-1)) exceeded all figures reported to date in other
      mammals and was apparently linked to the high FMR level and relatively high water
      content of shrews' food. Maximal metabolic rates (MMRRUN of 18.1+/-1.6 mL O2 g(
      1) h(-1) and MMRCOLD of 23.5+/-1.9 mL O2 g(-1) h(-1)) were not high in proportion
      to BMR or FMR that resulted in relatively narrow aerobic reserve in S. araneus:
      20% when calculated against the MMRRUN and 39% when compared with the MMRCOLD.
      Our study reveals that S. araneus has high energy costs of living and operates
      close to its physiological limits.

PMID- 16096984
TI  - The amino acids used in reproduction by butterflies: a comparative study of
      dietary sources using compound-specific stable isotope analysis.
AB  - It is a nutritional challenge for nectar-feeding insects to meet the amino acid
      requirements of oviposition. Here we investigate whether egg amino acids derive
      from larval diet or are synthesized from nectar sugar in four species of
      butterfly: Colias eurytheme, Speyeria mormonia, Euphydryas chalcedona, and
      Heliconius charitonia. These species exhibit a range of life history and differ
      in degree of shared phylogeny. We use 13C differences among plants to identify
      dietary sources of amino acid carbon, and we measure amino acid 13C using
      compound-specific stable isotope analysis. Egg essential amino acids derived
      solely from the larval diet, with no evidence for metabolic carbon remodeling.
      Carbon in nonessential amino acids from eggs derived primarily from nectar
      sugars, with consistent variation in amino acid turnover. There was no
      relationship between the nonessential amino acids of eggs and host plants,
      demonstrating extensive metabolic remodeling. Differences between species in
      carbon turnover were reflected at the molecular level, particularly by glutamate
      and aspartate. Essential amino acid 13C varied in a highly consistent pattern
      among larval host plants, reflecting a common isotopic "fingerprint" associated
      with plant biosynthesis. These data demonstrate conservative patterns of amino
      acid metabolism among Lepidoptera and the power of molecular stable isotope
      analyses for evaluating nutrient metabolism in situ.

PMID- 16096988
TI  - Heme-heme interactions in tetramers and dimers of hemoglobin subunits: DeVoe
      theory calculations.
AB  - Detectable exciton couplets arising from heme-heme interactions in the hemoglobin
      (Hb) tetramers of HbO(2) and deoxyHb were predicted by DeVoe theory. This
      prediction was supported by the observation of an exciton couplet in the CD
      difference spectrum between the Hb tetramer and the alphabeta dimer of HbCO. In
      this paper, DeVoe theory is used to calculate the heme-heme interactions in the
      CO complex of the Hb tetramer (alpha(2)beta(2)) and dimer (alphabeta), the
      systems studied by Goldbeck et al. The couplet strength of the resulting
      theoretical CD difference spectrum agrees well with experiment, thus confirming
      that heme-heme interactions contribute significantly to the CD of HbCO. Given
      that the heme-heme distances in HbCO are 25 A and more, it is highly likely that
      heme-heme interactions also contribute significantly to the CD of other multi
      heme proteins, e.g., cytochrome c(3), cytochrome oxidase, cytochrome bc(1), etc.,
      where the hemes are in closer proximity.

PMID- 16096989
TI  - Stereoselectivity of the reduced folate carrier in Caco-2 cells.
AB  - Stereoselectivity of the human reduced folate carrier (RFC1) was examined in Caco
      2 cells using methotrexate (l-amethopterin or l-MTX) and its antipode (d
      amethopterin or d-MTX) as model substrates. The initial uptake rate of folic acid
      (FA) was concentration dependent, with a K(m) value of approximately 0.6 microM.
      The Eadie-Hofstee plot of the RFC1-mediated FA uptake revealed a single component
      for FA uptake into Caco-2 cells, demonstrating that only RFC1 is involved in FA
      uptake. l-MTX inhibited FA uptake in a competitive manner with a K(i) value of
      approximately 2 microM, similar to the K(m) value of l-MTX. d-MTX also
      competitively inhibited FA uptake with a K(i) value being approximately 120
      microM, indicating that the affinity of d-MTX is ca. 60-fold less than that of l
      MTX. The stereoselectivity of human RFC1 observed in the present study was
      consistent not only with the stereoselectivity of rabbit RFC1 observed in rabbit
      intestinal brush border membrane vesicles but also with the reported differences
      in oral absorption of amethopterin enantiomers in humans.

PMID- 16096990
TI  - Chiral separation and CD characterisation of enantiomeric cyclotriphosphazene
      derivatives.
AB  - The gem-disubstituted cyclotriphosphazene 1 reacted with piperazine (pip) to give
      the piperazine-bridged derivative 2, which is expected to exist in meso and
      racemic forms because the two PCl (pip) groups are stereogenic. The proton
      decoupled (31)P NMR spectrum of 2 gave rise to two similar sets of ABX signals in
      a 1:1 ratio, consistent with formation of diastereoisomers. The meso and racemic
      forms of compound 2 were separated by column chromatography on silica gel and
      characterised by elemental analysis, mass spectrometry, (31)P NMR spectroscopy,
      and X-ray crystallography. Using HPLC with a chiral stationary phase, the racemic
      form of compound 2 was further separated into enantiomers, which were
      characterised by circular dichroism (CD) spectroscopy. This is the first report
      of the separation of enantiomers in the field of cyclophosphazene chemistry and
      hence the first CD spectra of derivatives in which the cyclophosphazene ring is
      at the chiral centre.

PMID- 16096991
TI  - Stable encapsulation of active enzyme by application of multilayer nanofilm
      coatings to alginate microspheres.
AB  - In an effort to improve the stability for long-term biosensor use, layer-by-layer
      self-assembly was explored as a potential technique to provide a diffusion
      barrier to encapsulated glucose oxidase inside alginate microspheres (<5 microm),
      fabricated using an emulsification technique. The total loss of encapsulated
      enzyme was reduced to less than 25 and 15% with the application of single PAH/PSS
      and crosslinked PAH/PAA coatings, respectively, in comparison to at least a 45%
      loss observed with uncoated and PDDA/PSS-coated microspheres. Furthermore, it was
      found that enzyme within PAH/PSS- and crosslinked PAH/PAA-coated spheres retained
      more than 84 and 60% of initial activity, respectively, after three months,
      whereas uncoated and PDDA/PSS-coated microspheres retained less than 20%.

PMID- 16096992
TI  - Novel copolyanhydrides combining strong inherent fluorescence and a wide range of
      biodegradability: synthesis, characterization and in vitro degradation.
AB  - In this work, a novel diacid monomer was synthesized in a very convenient scheme.
      The monomer is derived from naturally occurring products and emits strong
      fluorescence when polymerized to polyanhydride. The chemical structure of the
      monomer dCPS is as follows: HOC(O)ArOC(O)(CH2)2C(O)O--Ar--COOH. Copolyanhydrides
      composed of dCPS and sebacic acid were further prepared by melt
      copolycondensation, and characterized by IR, NMR, UV-Vis, DSC and fluorometry.
      The emission wavelength (lambda(em)) of the copolymers could be tuned by the
      excitation wavelength (lambda(ex)). Fluorescence intensity increased with the
      increase of dCPS content. The microspheres fabricated from the copolymer with
      dCPS content as low as 10% could be clearly visualized with fluorescence
      microscopy. Either blue or green images of the microspheres could be captured
      with an excitation of UV and visible light. The degradation rate of the
      copolyanhydrides decreased as the dCPS fraction increased, and the degradation
      duration could be modulated from several days to more than three months. In
      addition, it was found that the copolyanhydrides displayed surface degradation
      characteristics. In view of the advantages of the novel copolyanhydrides, such as
      easy preparation, unique inherent luminescent properties, and widely adjustable
      degradation rate, they might be useful for biomedical engineering.

PMID- 16096993
TI  - Binding of adenosine to pendant phenylboronate groups of thermoresponsive
      copolymer: a quantitative study.
AB  - Binding of adenosine to the thermosensitive copolymer of N-isopropylacrylamide
      and 3-(acrylamido)aminophenylboronic acid (82:18, Mn = 47,000 g . mol(-1)) was
      studied by equilibrium dialysis at 22 degrees C and 37 degrees C, in a 0.1 M
      glycine buffer containing 0.1 M NaCl at pH 9.2. The copolymer exhibited a the
      phase transition temperature (T(p)) of 26.5 degrees C under the above conditions.
      At 22 degrees C the binding of adenosine to the water-soluble copolymer was well
      described by a Langmuir model, accounting for preferential ionisation of the
      boronate-nucleoside complexes and, therefore, restricted reactivity of the rest
      of boronates. At saturation, the copolymer contained 38% of its phenylboronic
      acid groups in the form of complexes, whereas the association constant was 1,400
      M(-1). At 37 degrees C no binding of adenosine to thermally precipitated
      copolymer was found, presumably owing to interaction of the phenylboronates with
      hydrophobic segments of polyNIPAM. At high loading of the copolymer by the
      reversibly bound adenosine the T(p) steeply increases with increasing fraction of
      the phenylboronate-adenosine complexes in the chains. The increase of the T(p)
      observed above the saturating adenosine concentration (>1 x 10(-3) M, 22 degrees
      C) very probably testifies to competition of the nucleoside with hydrophobic
      polyNIPAM segments for binding to the pendant phenylboronates.

PMID- 16096994
TI  - A community-based telephone survey of panic disorder in Hong Kong.
AB  - Panic disorder (PD) is prevalent, impairing, under-recognized, and often
      mistreated. Previous surveys in Chinese communities indicate very low prevalence
      estimates and provide limited information about its clinical characteristics. A
      random telephone survey of the general population (age range, 15-60 years) in
      Hong Kong was conducted using a questionnaire that generated the Diagnostic and
      Statistical Manual of Mental Disorders (DSM)-IV-based diagnosis of PD, its
      symptom profile, help-seeking behavior, and health visit expenditure. Of 3,004
      interviews successfully completed, 3.89% of participants (n=117) met criteria of
      PD in the previous 6 months. Their demographic and clinical profile resembled
      that of their Western counterparts. Excessive physical investigations and under
      treatment were common. Participants with subthreshold PD (14.9%; n=449) exhibited
      a similar but attenuated clinical profile. We conclude that PD may be more common
      in Chinese people than what previous epidemiological surveys suggest. The present
      study is limited by the lack of clinical reappraisal, examination of comorbidity,
      and a low overall response rate. Nonetheless, it suggests that telephone
      interviews may provide a cost-effective alternative to large-scale
      epidemiological surveys for communities with limited resources for mental health
      research and high unmet needs for treatment.

PMID- 16096995
TI  - Variation in IRF6 contributes to nonsyndromic cleft lip and palate.
AB  - Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common
      craniofacial birth defect which results in lifelong medical and social
      consequences. While there have been a number of attempts to identify the genes
      responsible for this disorder, the results have not been consistent among
      populations and no single gene has been identified as playing a major
      susceptibility role. Van der Woude syndrome, a disorder characterized by lower
      lip pits with or without cleft lip/palate, results in many cases from mutations
      in the interferon regulatory factor 6 (IRF6) gene. Recently, Zucchero et al.
      [2004: N Engl J Med 351:769-780] detected an association between SNPs in IRF6 and
      NSCLP in a number of different populations. A subsequent study by Scapoli et al.
      [2005: Am J Hum Genet 76:180-183] confirmed this association in an Italian
      population. We examined the same SNPs as Scapoli et al. [2005] in our large, well
      characterized sample of NSCLP families and trios, and also detected an altered
      transmission of IRF6 alleles. This additional confirmation further strengthens
      the IRF6 association and suggests that IRF6 plays a role in NSCLP susceptibility.

PMID- 16096996
TI  - Acrofacial dysostosis (AFD) with preaxial limb hypoplasia (Nager AFD) and club
      foot diagnosed in a fetus from 1812 in the anatomical collections at the
      University of Halle, Germany.
AB  - The Anatomical Collections of the Department of Anatomy and Cell Biology at the
      University of Halle, Germany, comprise more than 8,000 specimens, about 600 of
      them congenital anomalies. The collection of abnormal human and animal specimens
      began with the private collections of Johann Friedrich Meckel the Elder (1724
      1774), his son Philipp Friedrich Theodor Meckel (1755-1803), and his grandson
      Johann Friedrich Meckel the Younger (1781-1833). Meckel the Younger founded the
      science of developmental pathology in Germany. Radiographical techniques,
      computer tomographic methods (CT), magnetic resonance imaging (MRI), and
      molecular cytogenetic techniques, for example, comparative genomic hybridization
      (CGH) were used to diagnose abnormal human fetuses in the Meckel Collection. On
      examination of one of the human fetuses, originally described by JF Meckel the
      Younger in 1812 or earlier, we found striking clinical manifestations including
      mandibulofacial defects and preaxially malformed limbs. With respect to external
      findings, we propose that the condition is acrofacial dysostosis (AFD) with
      preaxial limb hypoplasia (Nager AFD) in combination with club foot, tibial
      torsion, and single umbilical artery. We used genetic analyses to test whether
      the observed limb malformations could be caused by aneuploidy. CGH-ratio profiles
      of all chromosomes were apparently normal. It is likely that Meckel's specimen is
      the earliest known fetus with Nager AFD.

PMID- 16096997
TI  - Identification and study of Utah pseudo-isolate populations-prospects for gene
      identification.
AB  - Isolate populations of varied types have proven powerful for gene identification
      for rare Mendelian disorders, and continue to show such promise for more complex
      phenotypes. Existing isolate populations are limited in the phenotypes available
      for study, and new population isolates are unlikely to arise. We utilize
      genealogical data available for the state of Utah, dating back to its European
      founders, to retrospectively define and examine pseudo-isolate subpopulations.
      These pseudo-isolate populations are defined by selection of a set of "founders"
      from the genealogical data, and then limitation of "immigration" by censoring of
      matings and offspring that do not match the isolate population design. A wide
      variety of pseudo isolate and other study designs are possible by varying the
      number and type of founders and the extent of immigration allowed. We present
      several different example Birth-Country pseudo-isolate populations defined within
      the Utah Population Database (UPDB). We utilize linked cancer phenotype data
      available for the Utah population to show the utility of this pseudo-isolate
      approach for identification of more genetically homogeneous prostate cancer
      pedigrees for predisposition gene identification. In conclusion, we present a
      unique approach to retrospective "creation" of isolate populations using existing
      genealogical data. We use the UPDB to exhibit the utility of this approach for
      the highly heterogeneous Utah population, and suggest the approach is feasible
      for any population for which high quality genealogy and phenotype data are
      available.

PMID- 16096998
TI  - Juvenile onset Huntington disease resulting from a very large maternal expansion.
AB  - We report a 5(1/2)-year-old girl with a maternal family history of Huntington
      disease (HD), who presented clinically with unbalanced gait, impaired speech, and
      increasing difficulty with fine motor control. Onset of symptoms began at the age
      of 3(1/2) years. The suspected diagnosis of juvenile HD, based upon her family
      history, was confirmed by DNA analysis. At age 7, the patient died secondary to
      complications of her underlying disorder. Juvenile-onset Huntington disease is
      uncommon, predominantly transmitted by fathers and is always associated with very
      large expansions of the CAG repeat. Interestingly, this patient inherited a large
      CAG size expansion from her mother, who herself had symptoms of HD at the age of
      18. Molecular analysis revealed that the mother had 70 CAG repeats whereas our
      patient had approximately 130 CAG repeats. This is the largest reported CAG
      expansion from a maternal transmission that has been confirmed molecularly and it
      demonstrates that very large expansions can also occur through the maternal
      lineage.

PMID- 16096999
TI  - Michels syndrome, Carnevale syndrome, OSA syndrome, and Malpuech syndrome:
      variable expression of a single disorder (3MC syndrome)?
AB  - We report on a 3-year-old girl with Michels syndrome, a rare condition
      characterized by craniosynostosis, blepharophimosis, ptosis, epicanthus inversus,
      cleft lip/palate, abnormal supra-umbilical abdominal wall, and mental deficiency.
      The phenotypic findings are compared with the six previously reported Michels
      cases, and with patients referred to as Carnevale, OSA, and Malpuech syndromes.
      Michels syndrome is characterized by cleft lip and palate, anterior chamber
      anomalies, blepharophimosis, epicanthus inversus, and craniosynostosis. Carnevale
      syndrome shows hypertelorism, downslanting palpebral fissures, ptosis, strabismus
      synophrys, large and fleshy ears, and lozenge-shaped diastasis around the
      umbilicus. OSA syndrome resembles Carnevale, with humeroradial synostoses, and
      spinal anomalies as extra features. Malpuech syndrome shows IUGR, hypertelorism,
      cleft lip and palate, micropenis, hypospadias, renal anomalies, and caudal
      appendage. All are autosomal recessive. Despite the presence of apparently
      distinctive key features, it appears that these four entities share multiple
      similarities in the facial Gestalt and the pattern of MCA. Those similarities
      lead us to postulate that they belong to the same spectrum, which could be
      referred to as "3MC syndrome" (Malpuech-Michels-Mingarelli-Carnevale syndrome).

PMID- 16097000
TI  - X-chromosome inactivation and telomere size in newborns resulting from
      intracytoplasmic sperm injection.

PMID- 16097001
TI  - Recognition of Smith-Lemli-Opitz syndrome (RSH) in the fetus: utility of
      ultrasonography and biochemical analysis in pregnancies with low maternal serum
      estriol.
AB  - Smith-Lemli-Opitz syndrome (SLOS), or RSH, is an autosomal recessive disorder
      caused by mutations of the gene encoding 7-dehydrocholesterol reductase (DHCR7).
      The utility of maternal serum screens and ultrasound as prenatal screening
      methods for SLOS is presently undetermined. We report the clinical, cytogenetic,
      biochemical, and molecular findings of a stillborn with SLOS. The diagnosis was
      made postnatally on the basis of physical findings and confirmed by biochemical
      and DNA analyses of fetal tissue. Although abnormalities were detected by
      maternal serum triple screen and prenatal ultrasonography, a diagnosis of SLOS
      was not suspected before delivery. This study demonstrates that patients with
      SLOS may escape prenatal diagnosis despite the presence of multiple anomalies and
      abnormal maternal serum screen results, and lends support for consideration of
      prenatal biochemical testing for SLOS in pregnancies with these findings. As SLOS
      is a severe autosomal recessive disorder with a recurrence risk of 25%,
      ultrasonographic, cytogenetic, and biochemical analyses in the second trimester
      should be considered if abnormal maternal serum screening results, specifically
      low levels of unconjugated estriol, are detected.

PMID- 16097002
TI  - A novel in-frame deletion in ARX is associated with lissencephaly with absent
      corpus callosum and hypoplastic genitalia.

PMID- 16097003
TI  - Chromosome 1q42 deletion and agenesis of the corpus callosum.

PMID- 16097004
TI  - Demonstration of two novel LAMB2 mutations in the original Pierson syndrome
      family reported 42 years ago.

PMID- 16097005
TI  - A new syndrome of congenital generalized osteosclerosis and bilateral
      polymicrogyria.
AB  - We report a 29-week male fetus with healthy consanguineous parents. He showed a
      severe sclerosing bone disorder affecting all skeletal elements, resulting in
      insufficient modeling, generalized densification, and fragility of the skeleton.
      This skeletal dysplasia was associated with an abnormal craniofacial development
      (hypertelorism, severe microretrognathia, cleft palate, absent epiglottis,
      reduced number, and mineralization of teeth buds) and abnormal terminal
      phalanges. Neuropathologic examination showed bilateral fronto-parietal cerebral
      polymicrogyria. This syndrome appears to represent a new variant of congenital
      sclerotic bone disorder of unknown origin. Autosomal recessive inheritance is
      possible.

PMID- 16097006
TI  - A novel missense mutation in a C2 domain of OTOF results in autosomal recessive
      auditory neuropathy.
AB  - Screening of 12 Turkish families with apparently autosomal recessive nonsyndromic
      sensorineural deafness without GJB2 and mtDNA m.1555A > G mutations for 11
      previously mapped recessive deafness loci showed a family in which hearing loss
      cosegregated with the DFNB9 (OTOF) locus. Three affected children were later
      found to carry a novel homozygous c.3032T > C (p.Leu1011Pro) mutation in the OTOF
      gene. Both parents were heterozygous for the mutation. p.Leu1011Pro alters a
      conserved leucine residue in the C2D domain of otoferlin. Pure tone audiometry of
      the family showed severe to profound sensorineural hearing loss (with U-shape
      audiograms) in children, and normal hearing in the parents. Otoacoustic emissions
      and auditory brainstem response (ABR) suggested the presence of auditory
      neuropathy in affected individuals.

PMID- 16097007
TI  - Duplication of Xq26.2-q27.1, including SOX3, in a mother and daughter with short
      stature and dyslalia.
AB  - Duplications of the distal long arm of the X chromosome are rare and carrier
      females are usually phenotypically normal. We report on a 14-year-old short
      statured (height and weight <3rd centile) girl with dup(X)(q26.2q27.1) inherited
      from a short mother. The proband has minor dysmorphic features, lordosis, lack of
      menarche, late signs of puberty, low prepuberal levels of gonadotrophins and
      steroids, but borderline low IGF-1 and normal IGF-Bp3 serum levels. Both the
      proposita and her mother have severe speech problems with stuttering and
      dyslalia. The 44-year-old mother with a strikingly aged face and a prominent
      nose, had menarche at 15 years. Both maternal sisters and the grandmother of the
      proposita are also short. Karyotyping revealed an additional band at Xq26 in all
      metaphases from the proband, her mother, and two maternal aunts. Molecular
      cytogenetic investigations revealed an Xq26.2-q27.1 direct duplication of
      approximately 7.5 Mb that encompasses or disrupts the SOX3 gene, which maps at
      the distal border of the duplicated segment. A similar chromosomal duplication
      was reported recently in five families and in each was associated with an
      abnormal phenotype in males with short stature [Hol et al., 2000; Solomon et al.,
      2002, 2004]. Using an androgen-receptor (HUMARA) gene methylation assay and FISH,
      we show that despite preferential inactivation of the dup(Xq) chromosome a
      significant proportion of lymphocytes in both mother and daughter carry an active
      duplicated X chromosome. Our findings further suggest that a dosage effect of
      SOX3 may to be responsible for a speech disorder in addition to short stature
      secondary to hypopituitarism.

PMID- 16097008
TI  - Probable identity-by-descent for a mutation in the Dyggve-Melchior-Clausen/Smith
      McCort dysplasia (Dymeclin) gene among patients from Guam, Chile, Argentina, and
      Spain.

PMID- 16097009
TI  - The natural history of severe anemia in cartilage-hair hypoplasia.
AB  - Anemia is seen in over 80% of patients with cartilage-hair hypoplasia (CHH).
      While this is usually mild and self-limited, some patients demonstrate a severe,
      persistent anemia resembling that seen in Diamond-Blackfan anemia (DBA). This
      paper examines the natural history of 12 patients with CHH and severe anemia.
      Phenotypic features and mutation data (where available) were reviewed, but no
      significant differences were found that predicted severe anemia. Severe anemia is
      estimated to occur in approximately 6% of CHH patients and is permanent in more
      than half of these patients. Thrombocytosis, though not previously reported in
      CHH, was noted in five patients, similar to that seen in DBA. The role of
      possible gene-gene and gene-environment interactions is discussed.

PMID- 16097010
TI  - Hollow-waveguide-based nanosecond, near-infrared pulsed laser ablation of tissue.
AB  - BACKGROUND AND OBJECTIVE: Short-pulse solid-state lasers have recently received
      much attention as new coherent light sources for medical applications, but steady
      transmission of their high-energy output pulses through a solid quartz fiber is
      difficult because of the onset of laser-induced breakdown. We previously
      demonstrated that hollow waveguides could be used to deliver nanosecond laser
      pulses for tissue ablation. The aim of this study was to determine the optimum
      laser pulse energy and range of defocused distance for obtaining a deep and sharp
      ablation channel in myocardial tissue with laser pulses transmitted through a
      hollow waveguide. STUDY DESIGN/MATERIALS AND METHODS: Cyclic-olefin-polymer
      coated silver hollow waveguides of 1 mm in inner diameter and 1 m in length were
      used. A vacuum-cored scheme was applied to the waveguides to suppress laser
      induced air breakdown. Porcine myocardial tissue was irradiated with 300 laser
      pulses that were delivered through the waveguide in vitro at various laser energy
      levels and defocused distances, and depths and diameters of channels were
      measured. Histological analysis of the ablated tissues was also performed.
      RESULTS: At an ablation energy of approximately 60 mJ/pulse, deep (>4.5 mm) and
      sharp (depth-to-diameter ratio of > 6) channels were created in tissue in the
      range of defocused distances of -4 approximately + 0.5 mm. Under these
      conditions, waveguide bending did not cause a remarkable change in ablation
      characteristics. Histological analysis of ablated tissue showed limited thermal
      damage but suggested a certain extent of mechanical effects in the tissue.
      CONCLUSION: With near-infrared, nanosecond laser pulses delivered through a
      cyclic-olefin-polymer-coated silver hollow waveguide, efficient and sharp
      ablation of myocardial tissue can be achieved, suggesting the usefulness of the
      hollow waveguide as a new flexible delivery system for high-intensity laser
      pulses.

PMID- 16097011
TI  - The cytoskeleton-dependent localization of cdc2/cyclin B in blastomere cortex
      during Xenopus embryonic cell cycle.
AB  - In the early development of the frog, Xenopus laevis, blastomeres undergo
      synchronous divisions at about the 12th cell cycle, followed by asynchronous
      divisions, which is referred to as mid-blastula transition (MBT). We investigated
      the distribution of several regulating factors for cell cycles around MBT using
      immunocytochemistry and confocal fluorescence microscopy. At the 8th cell cycle,
      most of the cdc2/cyclin B was localized in the cortical cytoplasm throughout the
      cell cycle, in the centrosomes and the nucleus at interphase and prometaphase,
      and in the spindles at metaphase and anaphase. Cdc2 was also localized in the
      chromatins at metaphase and anaphase. Cyclin B1 mRNA was localized in the
      periphery of the nucleus, but not in the cell cortex. At the 13th cell cycle, the
      amount of cdc2/cyclin B in the cortical cytoplasm decreased, and the inactive
      form of cdc2, phosphorylated at tyrosine 15, appeared in the nucleus and the
      centrosomes at interphase, indicating that the regulation of cdc2 by
      phosphorylation occurs around MBT. When the blastomeres were treated with
      nocodazole or latrunculin A at the 8th cell cycle, the amount of cortical cdc2
      decreased, but that of cyclin B did not change. The cortical localization of cdc2
      is dependent upon both microtubules and microfilaments. Most of the cdc27 was
      localized in the centrosomes, and in the spindle poles, but no significant
      difference was observed between the 8th and the 13th cell cycles. It is possible
      that the cortical MPF activity is regulated by the differential localization
      between cdc2 and cyclin B.

PMID- 16097012
TI  - Novel approach to the newborn with hypoplastic left heart syndrome and intact
      atrial septum.
AB  - A prenatally diagnosed fetus with hypoplastic left heart syndrome and intact
      atrial septum was delivered in the cardiac catheterization suite. Using radio
      frequency energy, a transseptal perforation of the thickened and intact atrial
      septum was immediately performed following transcatheter cannulation of the right
      atrium via the umbilical vein. Serial cutting balloon septostomies followed by
      static balloon septostomies resulted in effective left atrial decompression,
      atrial mixing, and optimal pulmonary and systemic perfusion. The child is now
      thriving after both stage I Norwood and bidirectional Glenn procedures.

PMID- 16097013
TI  - Congenital coronary anomalies in adults: comparison of anatomic course
      visualization by catheter angiography and electron beam CT.
AB  - The objective of this study was to compare the anatomic course of anomalous
      coronary arteries by axial and three-dimensional volume-rendered electron beam
      computed tomography (EBCT) angiography and X-ray catheter angiography (CAG). We
      performed a blinded study where patients who previously underwent CAG with (n =
      14) and without (n = 14; age- and gender-matched controls) anomalous coronary
      anatomy were studied with EBCT coronary angiography. Forty to 50 EKG-triggered 3
      mm overlapping axial slices were acquired with 2 mm table movement within one
      breath hold during the i.v. injection of 140 cc of nonionic iodinated contrast (4
      ml/sec). The axial source images and volume-rendered three-dimensional
      reconstructions were evaluated for the presence, type, and course of coronary
      anomalies and the results were compared to those of CAG. All normal and anomalous
      coronary arteries were identified by both modalities in all subjects. Identified
      anomalies include single coronary artery (n = 3), left-sided right coronary
      artery (n = 3), right-sided left main coronary artery (n = 3), anterior
      descending coronary artery (n = 2), circumflex coronary artery (n = 2), and
      separate left-sided ostia for left anterior descending and circumflex coronary
      arteries (n = 1). In five cases, there was discrepancy in the course of the
      anomalous vessels between the two modalities. Consensus reading among
      cardiologist and radiologists favored the interpretation of EBCT over catheter
      angiography. Noninvasive EBCT coronary angiography compares well with CAG in
      identifying anomalous coronary arteries and may provide confirmatory evaluation
      of their precise anatomic relationships to the heart and great vessels.

PMID- 16097014
TI  - Laryngeal reconstruction by platysma myofascial flap after vertical partial
      laryngectomy.
AB  - BACKGROUND: Many methods of glottic reconstruction have been described for
      patients undergoing vertical partial laryngectomy to reestablish the glottic
      integrity. METHODS: Fifteen patients with T2 squamous cell carcinoma of the
      glottis were included in this prospective clinical trial. All patients were
      treated by vertical partial laryngectomy with laryngeal reconstruction by
      platysma myofascial flap. The surgical procedure and flap design were described.
      Vocal function was assessed by videolaryngostroboscopy and subjective and
      objective voice analysis before and after surgery. RESULTS: Complete neoglottic
      closure and acceptable voice quality were obtained by platysma myofascial flap in
      all cases. No statistically significant difference was found between the
      preoperative and postoperative acoustic parameters. CONCLUSIONS: Platysma
      myofascial flap provides the basic requirements for laryngeal reconstruction with
      its own favorable characteristics and also allows complete glottic closure
      without interfering with respiration and deglutition. This technique may be an
      effective alternative achieving an acceptable quality of voice.

PMID- 16097015
TI  - Two molecular tapes consisting of serial or parallel azido-bridged eight-membered
      copper rings.

PMID- 16097016
TI  - Titanium-catalyzed intermolecular hydroamination of vinylarenes.

PMID- 16097017
TI  - Highly regio- and enantioselective asymmetric hydroformylation of olefins
      mediated by 2,5-disubstituted phospholane ligands.

PMID- 16097018
TI  - Intramolecular rotation through proton transfer: [Fe(eta5-C5H4CO2-)2] versus
      [(eta5-C5H4CO2-)Fe(eta5-C5H4CO2H)].

PMID- 16097019
TI  - General catalysts for the Suzuki-Miyaura and Sonogashira coupling reactions of
      aryl chlorides and for the coupling of challenging substrate combinations in
      water.

PMID- 16097020
TI  - Reversible expansion and contraction of a 1,2-diborylated ferrocene dimer
      promoted by redox chemistry and nucleophile binding.

PMID- 16097021
TI  - Enrichment of xanthohumol in the brewing process.
AB  - Xanthohumol (XN), a component of hops, is lost in significant quantities in the
      conventional brewing process. In commercial beers less than 0.2 mg XN/L are
      found. In order to increase the yield of XN in the brewing process, the
      parameters of XN recovery were studied. During wort boiling, XN is largely
      isomerised to isoxanthohumol. Further losses are owing to the precipitation and
      absorption of XN to yeast cells and haze particles and by filtration. The use of
      XN-enriched hop products combined with a late hop dosage during wort boiling
      proved to be effective in increasing the XN content in beer. The yield was
      further raised by a low-pitching rate and the abnegation of beer stabilisation.
      The use of dark malts had a positive effect on the XN recovery. Investigations of
      roasted malt extracts revealed several high-molecular substances that are able to
      form complexes with XN. These complexes proved to be stable in the brewing
      process. Depending on the addition of roasted malt or special XN-enriched roasted
      malt extracts, dark beers with more than 10 mg XN/L were achieved. Results
      obtained led to a brewing technology that produced on an industrial scale pale
      wheat beer with more than 1 mg XN/L.

PMID- 16097022
TI  - Characterization of hydroxyaromatic compounds in vegetable oils by capillary
      electrophoresis with direct injection in an oil-miscible KOH/propanol/methanol
      medium.
AB  - The separation of hydroxyaromatic compounds in vegetable oils, including
      synthetic antioxidants (3-tert-butyl-4-hydroxyanisol and 2,6-di-tert-butyl-4
      hydroxytoluene), E-vitamers and other natural oil components, by nonaqueous
      capillary electrophoresis in an oil-miscible background electrolyte (BGE) was
      investigated. The BGE contained 40 mM KOH in a methanol/1-propanol (PrOH) mixture
      (15:85 v/v). The oil samples were 1:1 diluted with PrOH and directly injected in
      the capillary. Under negative polarity (cathode at the injection end), the
      anionic solutes moved faster than the electroosmotic flow, being well-resolved
      among them and from the triacylglycerols. Using virgin palm, extra virgin olive,
      wheat germ, virgin soybean and other oils, the capability of the procedure to
      quickly yield a characteristic profile of the biophenols present in the sample
      was demonstrated. The alpha-, (beta + gamma)- (as unresolved pair) and delta
      tocopherols of a soybean oil sample were quantified.

PMID- 16097024
TI  - Electrophoresis-assisted open-tubular liquid chromatography/mass spectrometry for
      the analysis of lipooligosaccharide expressed by Campylobacter jejuni.
AB  - Lipooligosaccharide (LOS) is the major component of the external membrane of
      Campylobacter jejuni. LOS contains a hydrophobic moiety, lipid A, and a
      hydrophilic moiety, oligosaccharide. Due to the unique mimicry of human
      ganglioside structures and potential involvement in the induction of the
      autoimmune polyneuropathies, Guillain-Barre and Miller Fisher syndromes, the
      structural characterization of C. jejuni LOS has received much attention. We have
      been using capillary zone electrophoresis-mass spectrometry to analyze O
      deacylated LOS from C. jejuni. In an attempt to optimize the separation
      conditions, the effect of methanol on the separation of LOS was investigated. It
      was found that methanol resulted in stronger adsorption of LOS onto the wall of
      fused-silica capillary. In this paper, we applied this adsorption to perform
      electrophoresis-assisted open-tubular liquid chromatography electrospray mass
      spectrometry for the analysis of O-deacylated LOS mixtures from C. jejuni. The
      analytical potential of the proposed strategy for the analysis of O-deacylated
      LOS glycoforms from five bacterial colonies is demonstrated. Online tandem mass
      spectrometry is shown to provide a powerful tool for characterization of
      variations in the hexosamine backbone, phosphorylation of the lipid A, and sialic
      acid sequence information.

PMID- 16097023
TI  - Effect of polymer matrix and glycerol on rapid single-strand conformation
      polymorphism analysis by capillary and microchip electrophoresis for detection of
      mutations in K-ras gene.
AB  - We present the rapid single-strand conformation polymorphism (SSCP) analysis by
      capillary and microchip electrophoresis to detect the mutations in K-ras gene.
      Parameters that might affect the analysis of mutation in K-ras gene, such as the
      polymer and the additive in the sieving matrix, have been studied systematically.
      Under the optimal conditions, the analysis of seven mutants of K-ras gene could
      be finished within 10 min by capillary electrophoresis (CE). Furthermore, with
      the wild-type gene as the inner standard, the analysis accuracy of mutations
      could be improved. In addition, by studying the properties of polymer solutions,
      the matrix suitable for microchip electrophoresis was found, and the detection of
      mutations in K-ras gene could be further shortened to 1 min.

PMID- 16097025
TI  - Effect of background electrolyte on the estimation of protein hydrodynamic radius
      and net charge through capillary zone electrophoresis.
AB  - Two physicochemical models are proposed for the estimation of both hydrodynamic
      radius and net charge of a protein when the capillary zone electrophoretic
      mobility at a given protocol, the set of pK of charged amino acids, and basic
      data from Protein Data Bank are available. These models also provide a rationale
      to interpret appropriately the effects of solvent properties on protein
      hydrodynamic radius and net charge. To illustrate the numerical predictions of
      these models, experimental data of electrophoretic mobility available in the
      literature for well-defined protocols are used. Five proteins are considered:
      lysozyme, staphylococcal nuclease, human carbonic anhydrase, bovine carbonic
      anhydrase, and human serum albumin. Numerical predictions of protein net charges
      through these models compare well with the results reported in the literature,
      including those found asymptotically through protein charge ladder techniques.
      Model calculations indicate that the hydrodynamic radius is sensitive to changes
      of the protein net charge and hence it cannot be assumed constant in general.
      Also, several limitations associated with models for estimating protein net
      charge and hydrodynamic radius from protein structure, amino acid sequence, and
      experimental electrophoretic mobility are provided and discussed. These
      conclusions also show clear requirements for further research.

PMID- 16097026
TI  - Simultaneous separation of organomercury species by nonaqueous capillary
      electrophoresis using methanol containing acetic acid and imidazole.
AB  - A simple and rapid nonaqueous capillary electrophoresis method for simultaneous
      separation of four kinds of mercury species, namely inorganic mercury,
      methylmercury, ethylmercury, and phenylmercury, is reported. The effective
      mobilities of organomercury in aqueous and nonaqueous electrolytes were compared.
      Imidazole was confirmed not only as a co-ion for the separation but also as an
      online complexing reagent for mercury species. The optimum conditions for
      separation were achieved by using methanol solvent containing 0.15 M acetic acid
      and 15 mM imidazole as electrolyte. The sensitive detection of mercury species
      was accomplished at 191 nm.

PMID- 16097027
TI  - Determination of hydrazine, monomethylhydrazine, 1,1-dimethylhydrazine, and 1,2
      dimethylhydrazine by nonaqueous capillary electrophoresis with amperometric
      detection.
AB  - The present study is concerned with the application of nonaqueous capillary
      electrophoresis (NACE) with electrochemical detection (ED) to the separation and
      quantitative determination of hydrazine (Hy) and its methyl derivatives. The best
      performance of NACE-ED was found when using 4 mM sodium acetate/10 mM acetic
      acid/methanol: acetonitrile = 1:2 as the running buffer, with a bare platinum
      working electrode set at +1.0 V in an end-column amperometric detection cell. The
      choice and ratio of suitable solvents for the separation and injection media
      played an essential role for the performance characteristics of the method. The
      limits of detection for Hy, methylhydrazine, symmetrical dimethylhydrazine, and
      unsymmetrical dimethylhydrazine were 5, 2, 12, and 1 ng/mL, respectively. This is
      between one and two orders of magnitude lower than that achieved by previously
      reported CE-ED methods in aqueous buffer systems in conjunction with various
      types of chemically modified electrodes. The practical utility of the new NACE-ED
      methodology is demonstrated in terms of the determination of traces of Hys in
      spiked environmental samples containing a wide range of explosives and related
      compounds.

PMID- 16097028
TI  - Investigation of the effect of ionic strength of Tris-acetate background
      electrolyte on electrophoretic mobilities of mono-, di-, and trivalent organic
      anions by capillary electrophoresis.
AB  - The effect of ionic strength of the background electrolyte (BGE) composed of
      tris(hydroxymethyl)aminomethane (Tris) and acetic acid on the electrophoretic
      mobility of mono-, di- and trivalent anions of aliphatic and aromatic carboxylic
      and sulfonic acids was investigated by capillary zone electrophoresis (CZE).
      Actual ionic mobilities of the above anions were determined from their CZE
      separations in Tris-acetate BGEs of pH 8.1 to 8.2 in the 3 to 100 mM ionic
      strength interval at constant temperature (25 degrees C). It was found that the
      ionic strength dependence of experimentally determined actual ionic mobilities
      does not follow the course supposed by the classical Onsager theory. A steeper
      decrease of actual ionic mobilities with the increasing ionic strength of BGE and
      a higher estimated limiting mobility of the anions than that found in the
      literature could be attributed to the specific behavior of the Tris-acetate BGEs.
      Presumably, not only a single type of interaction of anionic analytes with BGE
      constituents but rather the combination of effects, such as ion association or
      complexation equilibria, seems to be responsible for the observed deviation of
      the concentration dependence of the actual ionic mobilities from the Onsager
      theory. Additionally, several methods for the determination of limiting ionic
      mobilities from CZE measured actual ionic mobilities were evaluated. It turned
      out that the determined limiting ionic mobilities significantly depend on the
      calculation procedure used.

PMID- 16097029
TI  - Comparison of methanol and acetonitrile as solvents for the separation of
      sertindole and its major metabolites by capillary zone electrophoresis.
AB  - Sertindole (1-[2-[4-[5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl]-1
      piperidinyl]ethyl]-2-imidazolidinone), an atypical antipsychotic drug, was
      separated by capillary electrophoresis from its two main metabolites
      norsertindole and dehydrosertindole. The low solubility of the analytes in water
      (octanol-water partition coefficient is about 10(5)) is overcome by the use of
      methanol (MeOH) and acetonitrile (ACN) as solvents for the background electrolyte
      (BGE). Mobilities were measured in BGEs with defined pH in a broad range. It was
      found that in MeOH the mobility of the analytes is mainly governed by acid-base
      equilibria, whereas in ACN other reactions like ion pairing and homo-conjugation
      play a pronounced role and lead to a complex pattern of the mobility as function
      of the pH. However, separation can be obtained in less than 10 min in both
      solvent systems.

PMID- 16097030
TI  - Proteomic analysis of differentially expressed proteins in hepatocellular
      carcinoma developed in patients with chronic viral hepatitis C.
AB  - Hepatocellular carcinoma (HCC) is a major complication of chronic viral hepatitis
      C. Therapy for HCC is still disappointing. It is thus of great importance to
      identify novel HCC markers for early detection of the disease, and tumor-specific
      proteins as potential therapeutic targets. We have used a proteomic approach to
      identify new proteins involved in HCC development. Four cases of HCC developing
      from chronic viral hepatitis C were analyzed by two-dimensional electrophoresis
      (2-DE), and results were compared to those of paired adjacent non-tumorous liver
      tissues. For MS fingerprinting, protein spots with differential intensity between
      HCC and non-tumorous liver were directly cut out of gels and processed for MALDI
      MS and nano-LC-ESI-MS/MS analysis. Approximately 850 spots were visualized in
      each gel. The comparative analysis of paired samples indicated that 345 protein
      spots showed significant differences in expression level between non-tumor and
      tumor tissue. Among the 345 protein spots analyzed, 238 spots corresponding to
      155 different proteins were identified; 49 proteins were up-regulated, whereas
      106 proteins were down-regulated. Among these 155 proteins, 91 proteins were
      regulated in at least three cases. Although 52 out of these 91 proteins have been
      already described by previous proteomic or transcriptomic studies, or are already
      known to be involved in hepatocarcinogenesis, this experiment revealed 39 new
      proteins differentially expressed in HCC developing from viral hepatitis C.
      Variations in protein accumulation were confirmed for two selected proteins
      (apolipoprotein E, chloride intracellular channel 1) by Western blotting in ten
      additional cases of HCC developing in patients with viral hepatitis C.

PMID- 16097031
TI  - Proteome analysis of embryo and endosperm from germinating tomato seeds.
AB  - Proteome analysis of embryo and endosperm tissues from germinating tomato seed
      was conducted using 1-DE, 2-DE, and MS. Mobilization of the most abundant
      proteins, which showed similar profiles in the two tissues, occurred first in the
      endosperm. CBB R-250 staining of 2-DE gels revealed 352 and 369 major protein
      spots in the embryo and endosperm, respectively, at 0 h. Of these, 75 major spots
      were selected, excised, in-gel digested with trypsin, and analyzed by MALDI-TOF
      MS and/or LC-ESI-Q/TOF-MS/MS. Peptide MS and MS/MS data were searched against
      publicly available protein and EST databases, and 47 proteins identified. Embryo
      specific proteins included a BAC19.13 homologue, whereas four proteins specific
      to the endosperm were tomato mosaic virus coat proteins related to defense
      mechanisms. The most abundant proteins both in the embryo and endosperm were seed
      storage proteins, i.e., legumins (11 spots), vicilins (11 spots), albumin (2
      spots). Housekeeping enzymes, actin-binding profilin, defense-related protein
      kinases, nonspecific lipid transfer protein, and proteins involved in general
      metabolism were also identified. The roles of some of the proteins identified in
      the embryo and endosperm are discussed in relation to seed germination in tomato.

PMID- 16097032
TI  - Subproteomic analysis of metal-interacting proteins in human B cells.
AB  - Metal-protein interactions are vitally important in all living organisms.
      Metalloproteins, including structural proteins and metabolic enzymes, participate
      in energy transfer and redox reactions or act as metallochaperones in metal
      trafficking. Among metal-associated diseases, T cell mediated allergy to nickel
      (Ni) represents the most common form of human contact hypersensitivity. With the
      aim to elucidate disease-underlying mechanisms such as Ni-specific T cell
      activation, we initiated a proteomic approach to identify Ni-interacting proteins
      in human B cells. As antigen presenting cells, B cells are capable of presenting
      MHC-associated Ni-epitopes to T cells, a prerequisite for hapten-specific T cell
      activation. Using metal-affinity enrichment, 2-DE and MS, 22 Ni-interacting
      proteins were identified. In addition to known Ni-binding molecules such as
      tubulin, actin or cullin-2, we unexpectedly discovered that at least nine of
      these 22 proteins belong to stress-inducible heat shock proteins or chaperonins.
      Enrichment was particularly effective for the hetero-oligomeric TRiC/CCT complex,
      which is involved in MHC class I processing. Blue Native/SDS electrophoresis
      analysis revealed that Ni-NTA-beads specifically retained the complete protein
      machinery, including the associated chaperonin substrate tubulin. The apparent Ni
      affinity of heat shock proteins suggests a new function of these molecules in
      human Ni allergy, by linking innate and adaptive immune responses.

PMID- 16097033
TI  - Peptide microarrays for the characterization of antigenic regions of human
      chromogranin A.
AB  - Microarraying peptides is a powerful proteomics technique for studying molecular
      recognition events. Since peptides have small molecular mass, they are not easily
      accessible when adsorbed onto solid supports. Moreover, peptides can lack a well
      defined three-dimensional structure, and therefore a correct orientation is
      essential to promote the interaction with their target. In this work, we
      investigated the suitability as a peptide array substrate of a glass slide coated
      with a copolymer of N,N-dimethylacrylamide, N,N-acryloyloxysuccinimide, and [3
      (methacryloyl-oxy)propyl]trimethoxysilyl. This polymeric surface was used as
      substrate for peptides in the characterization of linear antigenic sites of human
      chromogranin A, a useful tissue and serum marker for neuroendocrine tumors and a
      precursor of many biologically active peptides. The microarray support provided
      sufficient accessibility of the ligand, with no need for a spacer, as the polymer
      chains prevent interaction of immobilized peptides with substrate. In addition,
      the polymeric surface constitutes an aqueous micro-environment in which linear
      epitopes are freely exposed despite peptide random orientation. The results
      reported in this article are in accordance with those obtained in conventional
      ELISA assays using biotinylated and non-biotinylated peptides.

PMID- 16097034
TI  - Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase
      diagonal LC.
AB  - We present a phosphoproteomics approach using diagonal RP chromatography as the
      basic isolation principle. Phosphopeptides present in a tryptic digest of total
      cellular lysates were first enriched by Fe3+-immobilized metal ion affinity
      chromatography. Further sorting of the phosphopeptides took place in three steps.
      First, the resulting peptide mixture was fractionated over reversed-phase
      chromatography. Second, peptides present in each fraction were treated with
      phosphatases. Third, the dephosphorylated peptides were then more hydrophobic and
      shifted towards a later elution interval from the contaminating non
      phosphopeptides eluting at the same position as during the primary run. Since the
      phosphopeptides are isolated as their dephosphorylated form, additional proof for
      their original phosphorylation state was obtained by split-differential 16O-18O
      labeling. The method was validated with alpha-casein phosphopeptides and
      consecutively applied on HepG2 cells. We identified 190 phosphorylated peptides
      from 152 different proteins. This dataset includes 38 novel protein
      phosphorylation sites.

PMID- 16097035
TI  - Proteome analysis reveals adaptation of Pseudomonas aeruginosa to the cystic
      fibrosis lung environment.
AB  - Pseudomonas aeruginosa is known for the chronic lung colonization of cystic
      fibrosis (CF) patients in addition to eye, ear and urinary tract infections. With
      the underlying disease CF patients are predisposed to P. aeruginosa chronic lung
      infection, which leads to morbidity and mortality. In this study, we compared the
      protein expression profile of a CF lung-adapted P. aeruginosa strain C with that
      of the burn-wound isolate PAO. Differentially expressed proteins from the whole
      cell, membrane, periplasmic as well as extracellular fraction were identified.
      The whole-cell proteome of strain C showed down-regulation of several proteins
      involved in amino acid metabolism, fatty acid metabolism, energy metabolism and
      adaptation leading to a highly distinct proteome pattern for strain C in
      comparison to PAO. Analysis of secreted proteins by strain C compared to PAO
      revealed differential expression of virulence factors under non-inducing
      conditions. The membrane proteome of strain C showed modulation of the expression
      of porins involved in nutrient and antibiotic influx. The proteome of the
      periplasmic space of strain C showed retention of elastase despite that the equal
      amounts were secreted by strain C and PAO. Altogether, our results elucidate
      adaptive strategies of P. aeruginosa towards the nutrient-rich CF lung habitat
      during the course of chronic colonization.

PMID- 16097036
TI  - Interleukin-21 triggers both cellular and humoral immune responses leading to
      therapeutic antitumor effects against head and neck squamous cell carcinoma.
AB  - BACKGROUND: Interleukin-21 (IL-21) plays important roles in the regulation of T,
      B, and natural killer (NK) cells. We hypothesized that the cytokine may provide a
      novel immunotherapy strategy for cancer by stimulating both Th1 and Th2 immune
      responses. In this context, antitumor immunity induced by IL-21 was examined in
      mice bearing subcutaneous head and neck squamous cell carcinomas (HNSCC).
      METHODS: A plasmid vector encoding murine IL-21 was injected intravenously into
      mice with pre-established HNSCC tumors, either alone or in combination with a
      vector construct expressing IL-15. Cytotoxic T lymphocyte (CTL) and NK killing
      activities were evaluated by chrome release assays, while HNSCC-specific antibody
      was examined by flow cytometry and ELISA. RESULTS: Significant antitumor effects
      were obtained by repeated transfection with either the IL-21 or the IL-15 gene.
      Co-administration of both cytokine genes resulted in increased suppression of
      tumor growth, significantly prolonging the survival periods of the animals.
      Thirty percent of the tumor-bearing mice that received the combination therapy
      survived for more than 300 days, completely rejecting rechallenge with the tumor
      at a distant site. IL-21 induced significant elevation of HNSCC-specific CTL
      activity, while IL-21 and IL-15 augmented NK activity in an additive manner. IL
      21 gene transfer also promoted the production of tumor-specific IgG. CONCLUSIONS:
      In vivo transduction of the IL-21 gene elicits powerful antitumor immunity,
      including both humoral and cellular arms of the immune response, and results in
      significant suppression of pre-established HNSCC. Co-transfer of the IL-15 gene
      further improved the therapeutic outcome, mainly by augmenting NK tumoricidal
      activity. The biological effects of IL-21 may be in sharp contrast to those of
      conventional Th1 and Th2 cytokines, suggesting intriguing implications of this
      cytokine for the classical concept of Th1 vs. Th2 paradigm.

PMID- 16097037
TI  - Cognitive impairment associated with adjuvant therapy in breast cancer.
AB  - The purpose of this study was to determine whether cognitive function changes
      over time in women with breast cancer who received adjuvant therapy as compared
      to women with breast cancer who received no adjuvant therapy. Three groups of
      women (n = 46) were studied; groups 1 and 2 consisted of women with stage I or II
      breast cancer. Group 1 received chemotherapy and group 2 received chemotherapy
      plus tamoxifen. Group 3 consisted of women with ductal carcinoma in situ who
      received no chemotherapy or tamoxifen. Cognitive function was evaluated at three
      timepoints. Time 1 occurred after surgery and before chemotherapy initiation in
      groups 1 and 2. Time 1 for group 3 occurred post-surgery. Time 2 occurred within
      1 week after the conclusion of chemotherapy for groups 1 and 2 and at a
      comparable time for group 3. Time 3 occurred 1 year after Time 2. Women who
      received chemotherapy plus tamoxifen exhibited deterioration on measures of
      visual memory and verbal working memory and reported more memory complaints.
      Women who received chemotherapy alone also exhibited deteriorations in verbal
      working memory. Conversely, cognitive function scores improved in women who
      received no therapy, indicating practice effects. In conclusion, adjuvant
      chemotherapy in women with breast cancer can be associated with deteriorations in
      memory and this may persist over time. The addition of tamoxifen may lead to more
      widespread memory deficits.

PMID- 16097038
TI  - CD98, a novel marker of transient amplifying human keratinocytes.
AB  - Identification of plasma membrane markers of basal keratinocytes is essential for
      sorting basal cells and, subsequently, adult epidermal stem cells. In this study,
      we isolated caveolin-1-enriched microdomains from human HaCaT keratinocytes and
      identified proteins representing potential cell surface markers of the epidermis
      by a proteomic approach. The purification of this caveolae domain allowed us to
      characterize 53 proteins of which 26% were transmembrane and 32% associated
      membrane proteins. One of them, CD98, was found to be co-localized with beta1
      integrin at the plasma membrane of the basal keratinocytes of healthy human
      epidermis. We then isolated CD98-positive keratinocytes from fresh skin biopsies.
      Using clonogenic assays, we demonstrate that CD98 may be considered as a marker
      of transient amplifying human keratinocytes.

PMID- 16097039
TI  - Local stimulation of articular cartilage repair by transplantation of
      encapsulated chondrocytes overexpressing human fibroblast growth factor 2 (FGF-2)
      in vivo.
AB  - BACKGROUND: Defects of articular cartilage are an unsolved problem in
      orthopaedics. In the present study, we tested the hypothesis that gene transfer
      of human fibroblast growth factor 2 (FGF-2) via transplantation of encapsulated
      genetically modified articular chondrocytes stimulates chondrogenesis in
      cartilage defects in vivo. METHODS: Lapine articular chondrocytes overexpressing
      a lacZ or a human FGF-2 gene sequence were encapsulated in alginate and further
      characterized. The resulting lacZ or FGF-2 spheres were applied to cartilage
      defects in the knee joints of rabbits. In vivo, cartilage repair was assessed
      qualitatively and quantitatively at 3 and 14 weeks after implantation. RESULTS:
      In vitro, bioactive FGF-2 was secreted, leading to a significant increase in the
      cell numbers in FGF-2 spheres. In vivo, FGF-2 continued to be expressed for at
      least 3 weeks without leading to differences in FGF-2 concentrations in the
      synovial fluid between treatment groups. Histological analysis revealed no
      adverse pathologic effects on the synovial membrane at any time point. FGF-2 gene
      transfer enhanced type II collagen expression and individual parameters of
      chondrogenesis, such as the cell morphology and architecture of the new tissue.
      Overall articular cartilage repair was significantly improved at both time points
      in vivo. CONCLUSIONS: The data suggest that localized overexpression of FGF-2
      enhances the repair of cartilage defects via stimulation of chondrogenesis,
      without adverse effects on the synovial membrane. These results may lead to the
      development of safe gene-based therapies for human articular cartilage defects.

PMID- 16097040
TI  - Efficient non-viral transfection of adult neural stem/progenitor cells, without
      affecting viability, proliferation or differentiation.
AB  - BACKGROUND: Neurogenesis occurs in defined areas of the adult mammalian brain,
      including the dentate gyrus of the hippocampus. Rat neural stem/progenitor cells
      isolated from this region retain their multipotency in vitro and in vivo after
      grafting into the adult brain. Molecular signalling and lineage selection in
      these cells may be examined using genetic manipulation. However, valid analysis
      requires that this manipulation should not affect cellular viability,
      proliferation or differentiation. METHODS: We screened several transfection
      protocols to develop a method which met these criteria. We then tested the
      effects of transfection on viability, proliferation and differentiation into the
      three neural lineages: neurons, astrocytes and oligodendrocytes. RESULTS: In
      initial testing, ExGen500 and FuGene6 efficiently transfected adult neural
      stem/progenitor cells, in vitro. After optimisation, these agents transfected 16%
      and 11% of cells, respectively. FuGene6-treated cells did not differ from
      untransfected cells in their viability or rate of proliferation, whereas these
      characteristics were significantly reduced following ExGen500 transfection.
      Importantly, neither agent affected the pattern of differentiation following
      transfection. Both agents could be used to genetically label cells, and track
      their differentiation into the three neural lineages, after grafting onto ex vivo
      organotypic hippocampal slice cultures. CONCLUSIONS: These data demonstrate that
      non-viral transfection may be used to genetically manipulate neural
      stem/progenitor cells, without adversely affecting their growth or perturbing
      lineage selection. Such a method is valuable for examining the molecular
      mechanisms of cell fate determination in vitro. Furthermore, this protocol may be
      exploited in the development of cell-based gene therapy strategies.

PMID- 16097041
TI  - Assessing the impact of cancer: development of a new instrument for long-term
      survivors.
AB  - OBJECTIVE: To develop and evaluate a new instrument that measures aspects of long
      term survivorship not measured by existing tools. METHODS: In qualitative
      interviews, 47 long-term cancer survivors (LTS) detailed ways that cancer has
      impacted their lives. Content analysis resulted in the creation of 325 candidate
      items for inclusion in a new Impact of Cancer (IOC) instrument. Following expert
      review, item reduction and pilot testing, 81 items were administered with other
      established health status and quality of life (QOL) instruments to 193 LTS of
      breast, prostate, colorectal cancers and lymphoma. Internal consistency
      reliability and validity of newly-derived scales was assessed. RESULTS: Factor
      analysis of items using a priori QOL domains resulted in the derivation of ten
      new and specific subscales: Health Awareness, Body Changes, Health Worries,
      Positive and Negative Self-Evaluation, Positive and Negative Life Outlook, Social
      Life Interferences, Relationships, and Meaning of Cancer. Internal consistency
      measurements for these subscales ranged from 0.67 to 0.89. Expected associations
      within and among the IOC subscales and standardized measures of health status and
      QOL were observed, as were some unexpected findings. CONCLUSIONS: Psychometric
      analysis indicated that this initial version of the Impact of Cancer instrument
      measures distinct and relevant constructs for LTS. Future work is necessary to
      confirm the factor structure, responsiveness and further validation of the
      instrument.

PMID- 16097042
TI  - Bio-feedback treatment of fecal incontinence: where are we, and where are we
      going?
AB  - Fecal incontinence is a disabling disease, often observed in young subjects, that
      may have devastating psycho-social consequences. In the last years, numerous
      evidences have been reported on the efficacy of bio-feedback techniques for the
      treatment of this disorder. Overall, the literature data claim a success rate in
      more than 70% of cases in the short term. However, recent controlled trials have
      not confirmed this optimistic view, thus emphasizing the role of standard care.
      Nonetheless, many authors believe that this should be the first therapeutic
      approach for fecal incontinence due to the efficacy, lack of side-effects, and
      scarce invasiveness. Well-designed randomized, controlled trial are eagerly
      awaited to solve this therapeutic dilemma.

PMID- 16097043
TI  - Preventing prolonged post-operative ileus in gastric cancer patients undergoing
      gastrectomy and intra-peritoneal chemotherapy.
AB  - AIM: To assess the efficacy of metoclopramide (Met) for prevention of prolonged
      post-operative ileus in advanced gastric cancer patients undergoing D2
      gastrectomy and intra-peritoneal chemotherapy (IPC). METHODS: Thirty-two advanced
      gastric cancer patients undergoing D2 gastrectomy and IPC were allocated to two
      groups. Sixteen patients received Met immediately after operation (group A), and
      16 did not (group B). Another 16 patients who underwent D2 gastrectomy without
      IPC were enrolled as the control group (group C). All patients had received
      epidural pain control. The primary endpoints were time to first post-operative
      flatus and time until oral feeding with a soft diet without discomfort. Secondary
      endpoints were early complications during hospitalization. RESULTS: Gender, the
      type of resection, operating time, blood loss, tumor status and amount of
      narcotics were comparable in the three groups. However, the group C patients were
      older than those in groups A and B (67.5+/-17.7 vs 56.8+/-13.2, 57.5+/-11.7
      years, P = 0.048). First bowel flatus occurred after 4.35+/-0.93 d in group A,
      4.94+/-1.37 d in group B, and 4.71+/-1.22 d in group C (P>0.05). Oral feeding of
      a soft diet was tolerated 7.21+/-1.92 d after operation in group A, 10.15+/-2.17
      d in group B, and 7.53+/-1.35 d in group C (groups A and C vs group B, P<0.05).
      There was no significant difference in respect to the first flatus among the
      three groups. However, the time of tolerating oral intake with soft food in
      groups A and C patients was significantly shorter than that in group B patients.
      Levels of C-reactive protein (CRP) were significantly lower in group C and there
      was a more prominent and prolonged response in CRP level in patients undergoing
      IPC. The incidence of post-operative complications was similar in the three
      groups except for prolonged post-operative ileus. There was no increased risk of
      anastomotic leakage in patients receiving Met. CONCLUSION: The results suggest
      that a combination of intravenous Met and epidural pain control may be required
      to achieve a considerable decrease in time to resumption of oral soft diet in
      advanced gastric cancer patients who underwent gastrectomy and IPC. Furthermore,
      the administration of Met did not increase anastomotic leakage. Met has a role in
      the prevention of prolonged post-operative ileus.

PMID- 16097044
TI  - High concentrations of human beta-defensin 2 in gastric juice of patients with
      Helicobacter pylori infection.
AB  - AIM: Human beta-defensin (HBD)-1 and HBD-2 are endogenous antimicrobial peptides.
      Unlike HBD-1, the HBD-2 expression is augmented by Helicobacter pylori (H
      pylori). We sought to determine HBD-1 and HBD-2 concentrations in gastric juice
      during H pylori infection. METHODS: HBD-1 and HBD-2 concentrations were measured
      by radioimmunoassay in plasma and gastric juice of 49 H pylori-infected and 33
      uninfected subjects and before and after anti-H pylori treatment in 13 patients
      with H pylori-associated gastritis. Interleukin (IL)-1beta and IL-8
      concentrations in gastric juice were measured by enzyme-linked immunosorbent
      assay (ELISA). Histological grades of gastritis were determined using two biopsy
      specimens taken from the antrum and corpus. Reverse phase high performance liquid
      chromatography (RP-HPLC) was used to identify HBD-2. RESULTS: HBD-2
      concentrations in gastric juice, but not in plasma, were significantly higher in
      H pylori-positive than -negative subjects, albeit the post-treatment levels were
      unchanged. Immunoreactivity for HBD-2 was exclusively identified in H pylori
      infected mucosa by RP-HPLC. HBD-2 concentrations in gastric juice correlated with
      histological degree of neutrophil and mononuclear cell infiltration in the
      corpus. IL-1beta levels correlated with those of IL-8, but not HBD-2. Plasma and
      gastric juice HBD-1 concentrations were similar in H pylori-infected and
      uninfected subjects. CONCLUSION: Our results place the beta-defensins, especially
      HBD-2, in the front line of innate immune defence. Moreover, HBD-2 may be
      involved in the pathogenesis of H pylori-associated gastritis, possibly through
      its function as immune and inflammatory mediator.

PMID- 16097045
TI  - Effect of IL-10 on the expression of HSC growth factors in hepatic fibrosis rat.
AB  - AIM: To study the effect of IL-10 on the expression of growth factors-
      transforming growth factor-beta1 (TGF-beta1), epidermal growth factor (EGF),
      hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF) of
      hepatic stellate cells (HSCs) of hepatic fibrosis rat and the anti-fibrogenic
      role of exogenous IL-10. METHODS: Hepatic fibrosis was induced by CCl(4)
      administration intra-peritoneally. Sixty clean male Sprague-Dawley (SD) rats were
      randomly divided into three groups: normal control group (GN, 8 rats), hepatic
      fibrosis model group (GC, 28 rats) and IL-10 treated group (GI, 24 rats). At the
      beginning of the 7th and 11th wk, rats in each group were routinely perfused with
      pronase E and type IV collagenase through a portal vein catheter and the
      suspension obtained from the liver was spun by centrifugation with 11% Nycodenz
      density gradient to isolate HSCs. Histological examination was used to determine
      the degree of hepatic fibrosis. RT-PCR was employed to analyze mRNA expression
      from freshly isolated cells. Immunocytochemistry was performed to detect protein
      expression in primary cultured HSCs. RESULTS: Rat hepatic fibrosis was developed
      with the increase of injection frequency of CCl(4), and HSCs were successfully
      isolated. At the 7th and 11th wk, TGF-beta1, EGF, and HGF mRNA in GC increased
      obviously compared with GN (P = 0.001/0.042, 0.001/0.001, 0.001/0.001) and GI (P
      = 0.001/0.007, 0.002/0.001, 0.001/0.001). For TGF-beta1, no difference was
      observed between GI and GN. For EGF, mRNA level in GI increased compared with GN
      during the 7th wk (P = 0.005) and 11th wk (P = 0.049). For HGF, mRNA level in GI
      decreased compared with GN at the 7th wk (P = 0.001) and 11th wk (P = 0.021).
      Between these two time points, TGF-beta1 expression at the 7th wk was higher than
      that of the 11th wk (P = 0.049), but for EGF, the former was lower than the
      latter (P = 0.022). As for PDGF mRNA, there was no significant difference between
      these groups, but difference seemed to exist in protein levels. Results by
      immunocytochemistry of TGF-beta1 and EGF were paralleled with the above findings.
      CONCLUSION: The expression of TGF-beta1, EGF and HGF increased in HSC of hepatic
      fibrosis rat and decreased after treatment with IL-10. IL-10 plays an anti
      fibrogenic role by suppressing growth factors expression.

PMID- 16097046
TI  - Vitamin D receptor gene Tru9I polymorphism and risk for incidental sporadic
      colorectal adenomas.
AB  - AIM: Recent laboratory and epidemiological studies suggest that vitamin D is a
      potential agent for colorectal cancer prevention. Its function is partially
      mediated by the vitamin D receptor (VDR). The aim of this study was to
      investigate whether a novel G (allele "U") >A (allele "u") polymorphism (Tru9I)
      in the VDR intron 8 region is associated with risk for colorectal adenoma in a
      colonoscopy-based case-control study. METHODS: Genotyping for a total of 391
      subjects was carried out through PCR and restriction fragment length
      polymorphism. RESULTS: The frequencies of "U" and "u" alleles were 89.3% and
      10.7%, respectively. The "Uu" and "uu" genotypes were associated with decreased
      risk for adenoma (OR, 0.71; 95%CI, 0.40-1.25). The inverse association was more
      pronounced for multiple adenomas and adenomas that were larger had moderate or
      greater dysplasia, or were sessile: the odds ratios (ORs) were, 0.51 (95%CI, 0.21
      1.24), 0.37 (95%CI, 0.11-1.28), 0.68 (95%CI, 0.33-1.41), and 0.36 (95%CI, 0.13
      0.97) respectively. In joint/combined analyses, inverse associations were more
      obvious among those who had at least one "u" allele and also were younger (OR,
      0.60; 95%CI, 0.26-1.37), women (OR, 0.38; 95%CI, 0.17-0.88), did not smoke (OR,
      0.39; 95%CI, 0.13-1.23), or took NSAID (OR, 0.38; 95%CI, 0.12-1.25), but no
      evidence existed for interactions with calcium or vitamin D intake. CONCLUSION:
      Our findings suggest that the VDR Tru9I polymorphism may be associated with lower
      risk for colorectal adenoma, particularly in interaction with various risk
      factors, but not with calcium or vitamin D.

PMID- 16097047
TI  - Effects of four regulating-intestine prescriptions on pathology and
      ultrastructure of colon tissue in rats with ulcerative colitis.
AB  - AIM: To observe different histomorphologic changes of ulcerative colitis (UC)
      rats that were treated with four regulating-intestine prescriptions (FRIP), to
      investigate the curative effects of FRIP and to analyze their treatment
      mechanism. METHODS: The UC rat model was made by the method of 2,4-dinitro chloro
      benzene (DNCB) immunity and acetic acid local enema. Ninety-eight SD rats were
      randomly divided into seven groups, namely, the normal control group, model
      group, salicylazosulfapyridine (SASP) group, Wumeiwan (WMW) group, Baitouwengtang
      (BTWT) group, Senglingbaishusan (SLBSS) group, and Tongxieyaofang (TXYF) group.
      Each group had 14 rats (with equal ratio of male and female). The six animal
      model groups of UC -SASP, TXYF, WMW, BTWT, SLBSS, TXYF-were treated by distilled
      water except the normal control group. Changes of the rat's general conditions
      after treatment were respectively observed, the colon tissue damage scores were
      given out, the pathology of colonic mucosa and changes of ultrastructure were
      analyzed. RESULTS: Different pathological changes on histology were shown after
      treatment by FRIP. The colon tissue damage score in model group was higher than
      that of FRIP groups and SASP group (q = 4.59, 4.77, P<0.05 or q = 5.48, 6.25,
      5.97, P<0.01). The scores of WMW group, BTWT group and SLBSS group were lower
      than that of SASP (q = 4.13, P<0.05 or q = 5.31, 5.12, P<0.01). There was no
      remarkable difference between the damage score of TXYF group and SASP group (q =
      3.75, P>0.05). In addition, some apoptosis cells were found in the pathologic
      control group. CONCLUSION: The model made with DNCB and acetic acid was
      successful, and FRIP had better curative effect and WMW was the best curative
      effect, BTW, SLBSS and TXYF were similar to SASP, and we discovered that
      apoptosis was possibly related to UC.

PMID- 16097048
TI  - ACEI attenuates the progression of CCl4-induced rat hepatic fibrogenesis by
      inhibiting TGF-beta1, PDGF-BB, NF-kappaB and MMP-2,9.
AB  - AIM: Angiotensin II has pro-fibrotic function in the liver. Blockade of the renin
      angiotensin-aldosterone-system (RAAS) attenuates hepatic fibrosis. The aim of the
      present study was to determine the mechanism of angiotensin-converting enzyme
      inhibitor (ACEI) on the progression of rat hepatic fibrosis. METHODS: Forty male
      Wistar rats were divided into three groups. Model group (Mo): The rats were
      injected subcutaneously with 40% of CCl(4) 0.25 mL/100 g. Perindopril group (Pe):
      The rats were injected subcutaneously with 40% of CCl(4). Perindopril, equivalent
      to 2 mg/(kg.d), was administrated. Control group (Nc): the rats were treated with
      olive oil only. After 4 and 6 wk, the rats were killed. The liver sections were
      stained with Masson. The protein expressions of AT1R, TGF-beta1 and PDGF-BB were
      examined by Western blot. Nuclear factor kappaB (NF-kappaB) DNA binding activity
      was examined by EMSA (Electrophoretic gel mobility shift assay). Matrix
      metalloproteinase-2,9 (MMP-2,9) activity was assessed by zymography. Serum
      laminin (LN) and hyaluronic acid (HA) were measured using radioimmunoassays.
      RESULTS: Using Western blot, we clearly provided direct evidence for the
      expression of AT1R in liver. The expression was up-regulated when fibrogenesis
      occurred. Perindopril treatment significantly reduced mean fibrosis score,
      protein levels of AT1R, TGF-beta1 and PDGF-BB, serum levels of HA and LN, and the
      activity of MMP-2,9. NF-kappaB DNA binding activity markedly increased in model
      group, perindopril treatment considerably reduced NF-kappaB DNA binding activity.
      CONCLUSION: Perindopril attenuates CCl(4)-induced hepatic fibrogenesis of rat by
      inhibiting TGF-beta1, PDGF-BB, NF-kappaB and MMP-2,9.

PMID- 16097049
TI  - Screening and identification of proteins interacting with nucleostemin.
AB  - AIM: To identify the proteins interacting with nucleostemin (NS), thereby gaining
      an insight into the function of NS. METHODS: Yeast two-hybrid assay was performed
      to screen a human placenta cDNA library with the full length of NS as a bait. X
      Gal assay and beta-galactosidase filter assay were subsequently conducted to
      check the positive clones and the gene was identified by DNA sequencing. To
      further confirm the interaction of two proteins, the DNA fragment coding NS and
      the DNA fragment isolated from the positive clone were inserted into the
      mammalian expression vector pcDNA3 and pcDNA3-myc, respectively. Then, two
      plasmids were cotransfected into the COS-7 cells by DEAE-dextron. The total
      protein from the cotransfected cells was extracted and coimmunoprecipitation and
      Western blot were performed with suitable antibodies sequentially. RESULTS: Two
      positive clones that interacted with NS were obtained from human placenta cDNA
      library. One was an alpha isoform of human protein phosphatase 2 regulatory
      subunit B (B56) (PPP2R5A) and the other was a novel gene being highly homologous
      to the gene associated with spondylo paralysis. The co-immunoprecipitation also
      showed that NS specifically interacted with PPP2R5A. CONCLUSION: NS and PPP2R5A
      interact in yeast and mammalian cells, respectively, which is helpful for
      addressing the function of NS in cancer development and progression.

PMID- 16097050
TI  - Influence of continuous veno-venous hemofiltration on the course of acute
      pancreatitis.
AB  - AIM: To investigate whether continuous veno-venous hemofiltration (CVVH) in
      different filtration rate to eliminate cytokines would result in different
      efficiency in acute pancreatitis, whether the saturation time of filter membrane
      was related to different filtration rate, and whether the onset time of CVVH
      could influence the survival of acute pancreatitis. METHODS: Thirty-seven
      patients were classified into four groups randomly. Group 1 underwent low-volume
      CVVH within 48 h of the onset of abdominal pain (early CVVH, n = 9). Group 2
      received low-volume CVVH after 96 h of the onset of abdominal pain (late CVVH, n
      = 10). Group 3 underwent high-volume CVVH within 48 h of the onset of abdominal
      pain (early CVVH, n = 9). Group 4 received high-volume CVVH after 96 h of the
      onset of abdominal pain (late CVVH, n = 9). CVVH was sustained for at least 72 h.
      Blood was taken before hemofiltration, and ultrafiltrate was collected at the
      start of CVVH and every 12 h during CVVH period for the purpose of measuring the
      concentrations of TNF-alpha, IL-1beta and IL-6. The concentrations of TNF-alpha,
      IL-1beta and IL-6 were measured by swine-specific ELISA. The Solartron 1 255 B
      frequency response analyzer (British) was used to observe the resistance of
      filter membrane. RESULTS: The survival rate had a significant difference (94.44%
      vs 68.42%, P<0.01) high-volume and low-volume CVVH patients. The survival rate
      had also a significant difference (88.89% vs 73.68%, P<0.05) between early and
      late CVVH patients. The hemodynamic deterioration (MAP, HR, CVP) was less severe
      in groups 4 and 1 than that in group 2, and in group 3 than in group 4. The
      adsorptive saturation time of filters membranes was 120-180 min if the filtration
      rate was 1 000-4 000 mL/h. After the first, second and third new hemofilters were
      changed, serum TNF-alpha concentrations had a negative correlation with
      resistance (r: -0.91, -0.89, and -0.86, respectively in group 1; -0.89, -0.85,
      and -0.76, respectively in group 2; -0.88, -0.92, and -0.82, respectively in
      group 3; -0.84, -0.87, and -0.79, respectively in group 4). The decreasing extent
      of TNF-alpha, IL-1beta and IL-6 was significantly different between group 3 and
      group 1 (TNF-alpha P<0.05, IL-1beta P<0.05, IL-6 P<0.01), between group 4 and
      group 2 (TNF-alpha P<0.05, IL-1beta P<0.05, IL-6 P<0.01), between group 1 and
      group 2 (TNF-alpha P<0.05, IL-1beta P<0.05, IL-6 P<0.05), and between group 3 and
      group 4 (TNF-alpha P<0.01, IL-1beta P<0.01, IL-6 P<0.05), respectively during
      CVVH period. The decreasing extent of TNF-alpha and IL-1beta was also
      significantly different between survival patients and dead patients (TNF-alpha
      P<0.05, IL-1beta P<0.05). In survival patients, serum concentration of TNF-alpha
      and IL-1beta decreased more significantly than that in dead patients. CONCLUSION:
      High-volume and early CVVH improve hemodynamic deterioration and survival in
      acute pancreatitis patients. High-volume CVVH can eliminate cytokines more
      efficiently than low-volume CVVH. The survival rate is related to the decrease
      extent of TNF-alpha and IL-1beta. The adsorptive saturation time of filter
      membranes are different under different filtration rate condition. The filter
      should be changed timely once filter membrane adsorption is saturated.

PMID- 16097051
TI  - Leptin administration exacerbates thioacetamide-induced liver fibrosis in mice.
AB  - AIM: To investigate the effects of leptin administration on liver fibrosis
      induced by thioacetamide (TAA). METHODS: Twenty-four male C57Bl/6 mice were
      randomly allocated into four groups, which were intra-peritoneally given saline
      (2 mL/kg), leptin (1 mg/kg), TAA (200 mg/kg), TAA (200 mg/kg) plus leptin (1
      mg/kg) respectively, thrice a week. All mice were killed after 4 wk. The changes
      in biochemical markers, such as the levels of alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) in serum and superoxide dismutase (SOD),
      malondialdehyde (MDA) in liver were determined. For histological analysis, liver
      tissues were fixed with 10% buffered formalin, embedded with paraffin.
      Hematoxylin-eosin (HE) staining and picric acid-Sirius red dyeing were performed.
      The level of alpha1(I) procollagen mRNA in liver tissues was analyzed by RT-PCR.
      RESULTS: Apparent liver fibrosis was found in TAA group and TAA plus leptin
      group. Compared to saline group, the levels of ALT and AST in serum and MDA in
      liver increased in TAA group (205.67+/-27.69 U/L vs 50.67+/-10.46 U/L, 177.50+/
      23.65 U/L vs 76.33+/-12.27 U/L, 2.60+/-0.18 nmol/mg pro vs 1.91+/-0.14 nmol/mg
      pro, P<0.01) and in TAA plus leptin group (256.17+/-22.50 U/L vs 50.67+/-10.46
      U/L, 234.17+/-27.37 U/L vs 76.33+/-12.27 U/L, 2.97+/-0.19 nmol/mg pro vs 1.91+/
      0.14 nmol/mg pro, P<0.01). The level of SOD in livers decreased (51.80+/-8.36
      U/mg pro vs 81.52+/-11.40 U/mg pro, 35.78+/-6.11 U/mg pro vs 81.52+/- 11.40 U/mg
      pro, P<0.01) and the level of alpha1(I) procollagen mRNA in liver tissues also
      increased (0.28+/-0.04 vs 0.11+/- 0.02, 0.54+/-0.07 vs 0.11+/-0.02, P<0.01). But
      no significant changes were found in leptin group and saline group. Compared to
      TAA group, ALT, AST, MDA, and alpha1(I) procollagen mRNA and grade of liver
      fibrosis in TAA plus leptin group increased (256.17+/-22.50 U/L vs 205.67+/-
      27.69 U/L, P<0.05; 234.17+/-27.37 U/L vs 177.50+/-23.65 U/L, P<0.05; 2.97+/-0.19
      nmol/mg pro vs 2.60+/-0.18 nmol/mg pro, P<0.05; 0.54+/-0.07 vs 0.28+/-0.04,
      P<0.01; 3.17 vs 2.00, P<0.05), and the level of SOD in liver decreased (35.78+/
      6.11 U/mg pro vs 51.80+/-8.36 U/mg pro, P<0.05). There were similar changes in
      the degree of type I collagen deposition confirmed by picric acid-Sirius red
      dyeing. CONCLUSION: Leptin can exacerbate the degree of TAA-induced liver
      fibrosis in mice. Leptin may be an important factor in the development of liver
      fibrosis.

PMID- 16097052
TI  - GFAP and Fos immunoreactivity in lumbo-sacral spinal cord and medulla oblongata
      after chronic colonic inflammation in rats.
AB  - AIM: To investigate the response of astrocytes and neurons in rat lumbo-sacral
      spinal cord and medulla oblongata induced by chronic colonic inflammation, and
      the relationship between them. METHODS: Thirty-three male Sprague-Dawley rats
      were randomly divided into two groups: experimental group (n = 17), colonic
      inflammation was induced by intra-luminal administration of
      trinitrobenzenesulfonic acid (TNBS); control group (n = 16), saline was
      administered intra-luminally. After 3, 7, 14, and 28 d of administration, the
      lumbo-sacral spinal cord and medulla oblongata were removed and processed for
      anti-glial fibrillary acidic protein (GFAP), Fos and GFAP/Fos
      immunohistochemistry. RESULTS: Activated astrocytes positive for GFAP were mainly
      distributed in the superficial laminae (laminae I-II) of dorsal horn,
      intermediolateral nucleus (laminae V), posterior commissural nucleus (laminae X)
      and anterolateral nucleus (laminae IX). Fos-IR (Fos-immunoreactive) neurons were
      mainly distributed in the deeper laminae of the spinal cord (laminae III-IV, V
      VI). In the medulla oblongata, both GFAP-IR astrocytes and Fos-IR neurons were
      mainly distributed in the medullary visceral zone (MVZ). The density of GFAP in
      the spinal cord of experimental rats was significantly higher after 3, 7, and 14
      d of TNBS administration compared with the controls (50.4+/-16.8, 29.2+/-6.5,
      24.1+/-5.6, P<0.05). The density of GFAP in MVZ was significantly higher after 3
      d of TNBS administration (34.3+/-2.5, P<0.05). After 28 d of TNBS administration,
      the density of GFAP in the spinal cord and MVZ decreased and became comparable to
      that of the controls (18.0+/-4.9, 14.6+/-6.4, P>0.05). CONCLUSION: Astrocytes in
      spinal cord and medulla oblongata can be activated by colonic inflammation. The
      activated astrocytes are closely related to Fos-IR neurons. With the recovery of
      colonic inflammation, the activity of astrocytes in the spinal cord and medulla
      oblongata is reduced.

PMID- 16097053
TI  - Crohn's disease in Japanese is associated with a SNP-haplotype of N
      acetyltransferase 2 gene.
AB  - AIM: To investigate the frequency and distribution of N-acetyltransferase 2
      (NAT2) and uridine 5'-diphosphate (UDP)-glucuronosyltransferase 1A7 (UGT1A7)
      genes in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS:
      Frequencies and distributions of NAT2 and UGT1A7 SNPs as well as their haplotypes
      were investigated in 95 patients with UC, 60 patients with CD, and 200 gender
      matched, unrelated, healthy, control volunteers by PCR-restriction fragment
      length polymorphism (RFLP), PCR-denaturing high-performance liquid chromatography
      (DHPLC), and direct DNA sequencing. RESULTS: Multiple logistic regression
      analysis revealed that the frequency of haplotype, NAT2*7B, significantly
      increased in CD patients, compared to that in controls (P = 0.0130, OR = 2.802,
      95%CI = 1.243-6.316). However, there was no association between NAT2 haplotypes
      and UC, or between any UGT1A7 haplotypes and inflammatory bowel disease (IBD).
      CONCLUSION: It is likely that the NAT2 gene is one of the determinants for CD in
      Japanese. Alternatively, a new CD determinant may exist in the 8p22 region, where
      NAT2 is located.

PMID- 16097054
TI  - Sonographic fatty liver, overweight and ischemic heart disease.
AB  - AIM: To demonstrate the prevalence of sonographic fatty liver, overweight and
      ischemic heart disease (IHD) among the male workers in Taiwan, and to investigate
      the possible association of these three factors. METHODS: From July to September
      2003, a total of 2 088 male aircraft-maintenance workers aged from 22 to 65 years
      (mean 40.5) underwent an annual health examination, including anthropometrical
      evaluation, blood pressure measurement, personal medical history assessment,
      biochemical blood analysis, abdominal ultrasonographic examination and digital
      electrocardiography (ECG). The Student's t-test, chi(2) test and multivariate
      logistic regression analysis were utilized to evaluate the relationship between
      IHD and salient risk factors. RESULTS: The all-over prevalence of overweight was
      41.4%, and that of fatty liver was 29.5% (mild, moderate and severe fatty liver
      being 14.5%, 11.3%, and 3.7%, respectively); while the prevalence of ischemic
      changes on ECG was 17.1% in this study. The abnormal rates for conventional IHD
      risk factors including hypertension, dyslipidemia, hyperglycemia and overweight
      increased in accordance with the severity of fatty liver. Overweight and severity
      of fatty liver were independently associated with increased risks for developing
      IHD. Overweight subjects had a 1.32-fold (95%CI: 1.01-1.73) increased IHD risk.
      Participants with mild, moderate, and severe fatty liver had a 1.88-fold (95%CI:
      1.37-2.6), 2.37-fold (95%CI: 1.66-3.37) and 2.76-fold (95%CI: 1.62-4.72)
      increased risk for developing IHD. The prevalence of ischemic ECG for the fatty
      liver-affected subjects with or without overweight was 30.1% and 19.1%, while
      that of overweight subjects free from fatty liver was 14.4%. Compared to the
      subjects without fatty liver nor overweight, IHD risk for the three subgroups
      above was as follows: OR: 2.95 (95%CI: 2.31-4.09), OR: 1.60 (95%CI: 1.07-2.39)
      and OR: 1.11 (95%CI: 0.78-1.56), respectively. CONCLUSION: The presence of fatty
      liver and its severity should be carefully considered as independent risk factors
      for IHD. Results of the study suggest the synergistic effect between fatty liver
      and overweight for developing IHD. Abdominal sonographic examination may provide
      valuable information for IHD risk assessment in addition to limited report about
      liver status, especially for overweight males.

PMID- 16097055
TI  - Value of CT-guided core-needle biopsy in diagnosis and classification of
      malignant lymphomas using automated biopsy gun.
AB  - AIM: To evaluate the value of CT-guided core-needle biopsy in diagnosis and
      classification of malignant lymphomas. METHODS: From January 1999 to October
      2004, CT-guided core-needle biopsies were performed in 80 patients with suspected
      malignant lymphoma. Biopsies were performed with an 18-20 G biopsy-cut (CR Bard,
      Inc., Covington, GA, USA) needle driven by a spring-loaded Bard biopsy gun.
      RESULTS: A definite diagnosis and accurate histological subtype were obtained in
      61 patients with a success rate of 76.25% (61/80). Surgical sampling was
      performed in 19 patients (23.75%) with non-diagnostic core-needle biopsies. The
      success rate of CT-guided core-needle biopsy varied with the histopathologic
      subtypes in our group. The relatively high success rates of core-needle biopsy
      were noted in diffuse large B-cell non-Hodgkin's lymphoma (NHL, 88.89%) and
      peripheral T-cell NHL (90%). However, the success rates were relatively low in
      anaplastic large cell (T/null cell) lymphoma (ALCL, 44.44%) and Hodgkin's disease
      (HD, 28.57%) in our group. CONCLUSION: CT-guided core-needle biopsy is a reliable
      means of diagnosing and classifying malignant lymphomas, and can be widely
      applied in the management of patients with suspected malignant lymphoma.

PMID- 16097056
TI  - Modulation of gastric accommodation by duodenal nutrients.
AB  - AIM: To determine the relative potency and contribution of intestinal nutrients
      to net gastric accommodative relaxation and conscious perception. METHODS: In 12
      healthy subjects, we randomly tested duodenal loads of lipids and carbohydrates
      (12 mL administered in 4 min) at various caloric concentrations (0.0125-0.8
      kcal/mL) separated by 12-24 min wash-out periods of saline infusion. Maximal
      gastric relaxation was induced at the end of each experiment by i.v glucagon (5
      microg/kg), as reference. The reflex gastric response was measured by a barostat,
      and symptom perception by a 0-6 score questionnaire. RESULTS: Lipids induced a
      dose-response gastric relaxation with a steep and early rise. Maximal effect
      (179+/-42 mL relaxation) reached at a relatively low concentration (0.2 kcal/mL),
      maximal lipid-induced relaxation was 61+/-6% of the glucagon effect. By contrast,
      duodenal infusion of carbohydrates induced weaker relaxation that became
      significant only at the high end of the physiological concentration range (65+/
      14 mL with 0.8 kcal/mL). Intestinal nutrient loads, either of lipid or
      carbohydrates, did not induce significant changes in perception (0.6+/-0.4 and
      0.1+/-0.4 score increase for the highest concentrations, respectively).
      CONCLUSION: Chyme entering the small bowel induces nutrient-specific gastric
      relaxatory reflexes by a physiologically saturable mechanism. Normally, neither
      the intestinal nutrient load nor the gastric accommodative response is perceived.

PMID- 16097057
TI  - Overexpression of S100A4 is closely associated with progression of colorectal
      cancer.
AB  - AIM: To investigate whether S100A4 played an important role in the development or
      progression of colorectal cancer. METHODS: A total of 124 colorectal
      adenocarcinoma tissue specimens were analyzed by immunohistochemistry for the
      expression of S100A4 protein and subsequently investigated for the gene mutations
      in the coding region of S100A4 gene. The specimens were collected over a 3-year
      period in the laboratories at our large teaching hospital in Seoul, Republic of
      Korea. RESULTS: Normal colonic epithelium either failed to express or showed
      focal weak expression of S100A4. Moderate to strong cytoplasmic expression of
      S100A4 was seen in 69 (55.6%) of the 124 colorectal carcinoma tissue specimens.
      S100A4 expression was detected in 43 (69.4%) of 62 specimens with lymph node
      metastasis. Statistically, overexpression of S100A4 was significantly associated
      with Dukes' stage and lymph node metastasis. Nuclear staining was also observed
      in 24 (19.4%) of 124 samples and closely associated with Dukes' stage. However,
      there was no significant correlation between overexpression of S100A4 and other
      investigated clinico-pathologic parameters, including tumor localization, tumor
      size, and survival period. In mutational analysis, no gene mutation was found in
      the analyzed genomic area of colorectal cancer. CONCLUSION: Overexpression of
      S100A4 may be closely related with the aggressiveness of colorectal carcinoma.

PMID- 16097058
TI  - Intra-familial prevalence of hepatitis B virologic markers in HBsAg positive
      family members in Nahavand, Iran.
AB  - AIM: To determine the prevalence of hepatitis B in Nahavand and evaluate the
      HBsAg positive prevalence in families with a member who was confirmed to have HBV
      infection. METHODS: This study was performed in two phases. In the first phase, 1
      824 subjects in Nahavand city were selected. The interviewers visited the houses
      of chosen families to fill the questionnaire and take the blood samples. All
      subjects signed an informed consent before interviews and blood sampling. The
      samples were evaluated for HBV virologic markers. In the second phase, 115 HBsAg
      positive cases were enrolled and evaluated for HBV virologic markers. RESULTS:
      The prevalence of positive HBsAg in Nahavand was 2.3%. The most frequent
      relatives of index cases were sons and daughters (32.2% and 23.5% respectively).
      Twelve (11%) of all family members were HBsAg positive. Fifty (56.2%) were
      isolated HBsAb positive and only one person (2.5%) was isolated HBcAb positive.
      The higher rates of HBsAg marker were detected in the brothers (1-25%) and
      fathers (1-12.5%). The infection rate in husbands and wives of index cases was
      10%. Only two (16.7%) of all HBsAg-positive participants reported previous HBV
      vaccination. CONCLUSION: The prevalence of intra-familial HBV infection is lower
      in Nahavand of Iran compared to other studies. More attention should be paid to
      HBV vaccination and risk-lowering activities.

PMID- 16097059
TI  - Non-steroidal anti-inflammatory drug-induced small bowel injuries identified by
      double-balloon endoscopy.
AB  - AIM: To clarify clinical features of the NSAID-induced small bowel lesions using
      a new method of endoscopy. METHODS: This is a retrospective study and we analyzed
      seven patients with small bowel lesions while taking NSAIDs among 61 patients who
      had undergone double-balloon endoscopy because of gastro-intestinal bleeding or
      anemia between September 2000 and March 2004, at Jichi Medical School Hospital in
      Japan. Neither conventional EGD nor colonoscopy revealed any lesions of potential
      bleeding sources including ulcerations. Double-balloon endoscopy was carried out
      from oral approach in three patients, from anal approach in three patients, and
      from both approaches in one patient. RESULTS: Ulcers or erosions were observed in
      the ileum in six patients and in the jejunum in one patient, respectively. The
      ulcers were multiple in all the patients with different features from tiny
      punched out ulcers to deep ulcerations with oozing hemorrhage or scar. All the
      patients recovered uneventfully and had full resolution of symptoms after
      suspension of the drug. CONCLUSION: NSAIDs can induce injuries in the small bowel
      even in patients without any lesions in both the stomach and colon.

PMID- 16097060
TI  - Effect of oral erythromycin on gastric and small bowel transit time of capsule
      endoscopy.
AB  - AIM: To determine the effect of oral erythromycin on gastric and small bowel
      transit time of capsule endoscopy. METHODS: Consecutive patients who underwent
      capsule endoscopy during the 16-mo study period were either given 250 mg oral
      erythromycin, 1 h prior to swallowing the capsule endoscope or nothing. The
      gastric and small bowel transit time, and the small bowel image quality were
      compared. RESULTS: Twenty-four patients received oral erythromycin whereas 14
      patients were not given any prokinetic agent. Patients who received erythromycin
      had a significantly lower gastric transit time than control (16 min vs 70 min, P
      = 0.005), whereas the small bowel transit time was comparable between the two
      groups (227 min vs 183 min, P = 0.18). Incomplete small bowel examination was
      found in three patients of the control group and in one patient of the
      erythromycin group. There was no significant difference in the overall quality of
      small bowel images between the two groups. A marked reduction in gastric transit
      time was noted in two patients who had repeat capsule endoscopy after oral
      erythromycin. CONCLUSION: Use of oral erythromycin significantly reduces the
      gastric transit time of capsule endoscopy.

PMID- 16097061
TI  - Appendix is a priming site in the development of ulcerative colitis.
AB  - AIM: The role of the appendix has been highlighted in the pathogenesis of
      ulcerative colitis (UC). The aims of this study were to elucidate the immuno
      imbalances in the appendix of UC patients, and to clarify the role of the
      appendix in the development of UC. METHODS: Colonoscopic biopsy specimens of the
      appendix, transverse colon, and rectum were obtained from 86 patients with UC:
      active pancolitis (A-Pan; n = 15), active left-sided colitis (A-Lt; n = 25), A-Lt
      with appendiceal involvement (A-Lt/Ap; n = 10), inactive pancolitis (I-Pan; n =
      14), and inactive left-sided colitis (I-Lt; n = 22), and from controls. In the
      isolated mucosal T cells, the CD4/CD8 ratio and proportion of activated CD4+ T
      cells were investigated, and compared with controls. RESULTS: In the appendix,
      the CD4/CD8 ratio significantly increased in A-Lt and A-Lt/Ap. The ratio in the
      appendix also tended to increase in A-Pan. In the rectum, the ratio significantly
      increased in all UC groups. In the appendix, the proportion of CD4+CD69+ (early
      activation antigen) T cells significantly increased in all UC groups. In the
      rectum, the proportion of CD4+CD69+ T cells significantly increased only in A
      Pan. The proportion of CD4+HLA-DR+ (mature activation antigen) T cells
      significantly increased only in the rectum of A-Pan, but not in the other areas
      of any groups. CONCLUSION: The increased CD4/CD8 ratio and predominant
      infiltration of CD4+CD69+ T cells in the appendix suggest that the appendix is a
      priming site in the development of UC.

PMID- 16097062
TI  - Ursodeoxycholic acid and superoxide anion.
AB  - AIM: To investigate the ability of ursodeoxycholic acid (UDCA) to scavenge
      superoxide anion (O(2)(-)). METHODS: We assessed the ability of UDCA to scavenge
      (O(2)(-)) generated by xanthine-xanthine oxidase (X-XO) in a cell-free system and
      its effect on the rate of O(2)(-)-induced ascorbic acid (AA) oxidation in hepatic
      post-mitochondrial supernatants. RESULTS: UDCA at a concentration as high as 1
      mmol/L did not impair the ability of the X-XO system to generate O(2)(-), but
      could scavenge O(2)(-) at concentrations of 0.5 and 1 mmol/L, and decrease the
      rate of AA oxidation at a concentration of 100 micromol/L. CONCLUSION: UDCA can
      scavenge O(2)(-), an action that may be beneficial to patients with primary
      biliary cirrhosis.

PMID- 16097063
TI  - HBeAg negative serological status and low viral replication levels characterize
      chronic hepatitis B virus-infected women at reproductive age in Greece: a one
      year prospective single center study.
AB  - AIM: To evaluate the seroprevalence of hepatitis B surface antigen (HBsAg) in 13
      581 women at reproductive age and the hepatitis B e antigen (HBeAg)/anti-HBe
      status as well as serum hepatitis B virus (HBV)-DNA levels in a subgroup of
      HBsAg(+) pregnant women at labor in Greece. METHODS: Serological markers were
      detected using enzyme immunoassays. Serum HBV-DNA was determined by a sensitive
      quantitative PCR assay. Statistical analysis of data was based on parametric
      methodology. RESULTS: Overall, 1.156% of women were HBsAg(+) and the majority of
      them (71.3%) were Albanian. The prevalence of HBsAg was 5.1% in Albanian women,
      4.2% in Asian women and 1.14% in women from Eastern European countries. The
      prevalence of HBsAg in African (0.36%) and Greek women (0.29%) was very low. Only
      4.45% of HBsAg(+) women were also HBeAg(+) whereas the vast majority of them were
      HBeAg(-)/anti-HBe(+). Undetectable levels of viremia (<200 copies/mL) were
      observed in 32.26% of pregnant women at labor and 29.03% exhibited extremely low
      levels of viral replication (<400 copies/mL). Only two pregnant women exhibited
      extremely high serum HBV-DNA levels (>10 000 000 copies/mL), whereas 32.26%
      exhibited HBV-DNA levels between 1 500 and 40 000 copies/mL. CONCLUSION: The
      overall prevalence of HBsAg is relatively low among women at reproductive age in
      Greece but is higher enough among specific populations. The HBeAg(-)/anti-HBe(+)
      serological status and the extremely low or even undetectable viral replicative
      status in the majority of HBsAg(+) women of our study population, suggest that
      only a small proportion of HBsAg(+) women in Greece exhibit a high risk for
      vertical transmission of the infection.

PMID- 16097064
TI  - Alpha-lipoic acid protects against cholecystokinin-induced acute pancreatitis in
      rats.
AB  - AIM: Alpha-lipoic acid (ALA) has been used as an antioxidant. The aim of this
      study was to investigate the effect of alpha-lipoic acid on cholecystokinin (CCK)
      octapeptide induced acute pancreatitis in rats. METHODS: ALA at 1 mg/kg was intra
      peritoneally injected, followed by 75 microg/kg CCK-octapeptide injected thrice
      subcutaneously after 1, 3, and 5 h. This whole procedure was repeated for 5 d. We
      checked the pancreatic weight/body weight ratio, the secretion of pro
      inflammatory cytokines and the levels of lipase, amylase of serum. Repeated CCK
      octapeptide treatment resulted in typical laboratory and morphological changes of
      experimentally induced pancreatitis. RESULTS: ALA significantly decreased the
      pancreatic weight/body weight ratio and serum amylase and lipase in CCK
      octapeptide-induced acute pancreatitis. However, the secretion of IL-1beta, IL-6,
      and TNF-alpha were comparable in CCK octapeptide-induced acute pancreatitis.
      CONCLUSION: ALA may have a protective effect against CCK octapeptide-induced
      acute pancreatitis.

PMID- 16097065
TI  - There is no association between K469E ICAM-1 gene polymorphism and biliary
      atresia.
AB  - AIM: To determine whether there was an association between inter-cellular
      adhesion molecule-1 (ICAM-1) gene polymorphism and biliary atresia (BA), and to
      investigate the relationship between serum soluble ICAM-1 (sICAM-1) and clinical
      outcome in BA patients after surgical treatment. METHODS: Eighty-three BA
      patients and 115 normal controls were genotyped. K469E ICAM-1 polymorphism was
      analyzed using PCR assay. Serum sICAM-1 was determined using ELISA method from 72
      BA patients. In order to evaluate the association between these variables and
      their clinical outcome, the patients were categorized into two groups: patients
      without jaundice and those with persistent jaundice. RESULTS: There were no
      significant differences between BA patients and controls in terms of gender,
      K469E ICAM-1 genotypes, and alleles. The proportion of patients having serum
      sICAM-1 >=3 500 ng/mL in persistent jaundice group was significantly higher than
      that in the other group. In addition, there was no association between K469E ICAM
      1 polymorphism and the status of jaundice in BA patients after Kasai operation.
      CONCLUSION: ICAM-1 possibly plays an important and active role in the disease
      progression. However, the process is not associated with genetic variation of
      K469E ICAM-1 polymorphism.

PMID- 16097066
TI  - Lewis blood genotypes of peptic ulcer and gastric cancer patients in Taiwan.
AB  - AIM: The Lewis b (Le(b)) antigen has been implicated as a possible binding site
      for attachment of Helicobacter pylori (H pylori) to gastric mucosa. However,
      studies both supporting and denying this association have been reported in the
      literature. Differences in secretor (Se) genotype have been suggested as a
      possible reason for previous discrepancies. Therefore, we investigated the
      relationship between Le and Se genotypes and H pylori infection rates in people
      with peptic ulcer or gastric cancer. METHODS: Peripheral blood samples were
      obtained from 347 patients with endoscopic evidence of peptic ulcer disease (235
      cases of duodenal ulcer, 62 of gastric ulcer, and 50 of combined duodenal ulcer/
      gastric ulcer) and 51 patients with gastric cancer on endoscopy. Peripheral blood
      specimens from 101 unrelated normal volunteers were used as controls. Lewis
      phenotype was determined using an antibody method, whereas Le and Se genotypes
      were determined by DNA amplification and restriction enzyme analysis. Gastric or
      duodenal biopsies taken from patients with endoscopic evidence of peptic ulcer or
      gastric cancer were cultured for H pylori. Isolates were identified as H pylori
      by morphology and production of urease and catalase. The H pylori infection
      status was also evaluated by rapid urease test (CLO test), and urea breath test
      ((13)C-UBT). Results of studies were analyzed by chi-square test (taken as
      significant). RESULTS: H pylori was isolated from 83.7% (303/347) of patients
      with peptic ulcer disease. Statistical analysis did not show any significant
      difference in Lewis phenotype or genotype between patients with and without H
      pylori infection. No significant association was found between Lewis genotype and
      peptic ulcer or gastric cancer. CONCLUSION: Lewis blood genotype or phenotype may
      not play a role in the pathogenesis of H pylori infection. However, bacterial
      strain differences and the presence of more than one attachment mechanism may
      limit the value of epidemiological studies in elucidating this matter.

PMID- 16097067
TI  - Etoposide sensitizes CT26 colorectal adenocarcinoma to radiation therapy in
      BALB/c mice.
AB  - AIM: To investigate the combined effect of etoposide and radiation on CT26
      colorectal adenocarcinoma implanted into BALB/c mice. METHODS: We evaluated the
      radiosensitizing effect of etoposide on CT26 colorectal adenocarcinoma in a
      syngeneic animal model. BALB/c mice were subcutaneously implanted with CT26 cells
      and divided into four groups: control (intra-peritoneal salineX2) group,
      etoposide (5 mg/kg intra-peritoneallyX2) group, radiation therapy (RT 5 GyX2
      fractions) group, and combination therapy with etoposide (5 mg/kg intra
      peritoneally 1 h before radiation) group. RESULTS: Tumor growth was significantly
      inhibited by RT and combination therapy. The effect of combination therapy was
      better than that of RT. No significant changes were noted in body weight, plasma
      alanine aminotransferase, or creatinine in any group. The leukocyte count
      significantly but transiently decreased in the RT and combination therapy groups,
      but not in the etoposide and control groups. There was no skin change or hair
      loss in the RT and combination therapy groups. CONCLUSION: Etoposide can
      sensitize CT26 colorectal adenocarcinoma in BALB/c mice to RT without significant
      toxicity.

PMID- 16097068
TI  - Disulfide-stabilized single-chain antibody-targeted superantigen: construction of
      a prokaryotic expression system and its functional analysis.
AB  - AIM: To construct the expression vector of B3 (scdsFv)-SEA (D227A) and to
      identify its binding and cytotoxic ability to B3 antigen positive carcinoma cell
      lines. METHODS: This fusion protein was produced by a bacterial expression system
      in this study. It was expressed mainly in the inclusion body. The gene product
      was solubilized by guanidine hydrochloride, refolded by conventional dilution
      method, and purified using SP-sepharose cation chromatography. RESULTS: The
      expression vector B3 (scdsFv)-SEA-PET was constructed, the expression product
      existed mainly in the inclusion body, the refolding product retained the binding
      ability of the single-chain antibody and had cytotoxic effect on HT-29 colon
      carcinoma cells. The stability assay showed that the resulting protein was stable
      at 37 degrees. CONCLUSION: This genetically engineered B3 (scdsFv)-SEA fusion
      protein has bifunction of tumor targeting and tumor cell killing and shows its
      promises as an effective reagent for tumor-targeted immunotherapy.

PMID- 16097069
TI  - Microsatellite instability in gastric cancer and pre-cancerous lesions.
AB  - AIM: To investigate the microsatellite instability (MSI) in cancer and pre
      cancerous lesions of the stomach and its mechanisms underlying the development of
      gastric cancer. METHODS: Thirty-six gastric cancer samples were obtained from
      patients undergoing surgery. Forty-one gastric mucosa samples with dysplasia and
      51 with intestinal metaplasia (IM) were obtained from patients with chronic
      gastritis undergoing gastro-endoscopy. Genomic DNA was extracted from the
      samples. Silver staining single strand conformation polymorphis-polymerize chain
      reaction (SSCP-PCR) was used to screen MSI markers at 5 loci (Bat-25, Bat-26,
      D5S346, D17S250, and D2S123) in fresh tissues and formalin-fixed, paraffin
      embedded samples and their corresponding normal gastric mucosa. RESULTS: The
      abnormal shifting of the single-strand DNA (MSI) was identified in 21 out of 36
      (58.3%) gastric cancers. Seven cases showed high-level MSI (two or more loci
      altered) and 14 showed low-level MSI (one locus altered). Gastric cancer with MSI
      had a tendency to be located in the distal stomach. MSI was also detected in 11
      out of 41 (26.8%) dysplasia samples and in 9 of 51 (17.6%) IM samples
      respectively. Three cases of dysplasia and one case of IM showed high-level MSI.
      Eight cases of dysplasia and 8 cases of IM displayed low-level MSI. MIS in IM was
      found only in moderate or severe-grade IM. No association was detected between
      MSI and dysplasia grade. CONCLUSION: Accumulation of MSI in dysplasia and
      intestinal metaplasia of gastric mucosa may be an early molecular event during
      gastric carcinogenesis and may contribute to the acquisition of transformed cell
      phenotype and the development of gastric cancer.

PMID- 16097070
TI  - Expression of cyclooxygenase-2 in gastric cancer and its relation to liver
      metastasis and long-term prognosis.
AB  - AIM: To investigate the expression of cyclooxygenase-2 (COX-2) in gastric cancer
      and its relation with the liver metastasis and prognosis. METHODS: Expression of
      COX-2 mRNA and protein was examined in gastric cancer and its paired substantial
      normal tissue by semi-quantitative reverse transcription-polymerase chain
      reaction and immunohistochemistry. The relation between COX-2 expression and
      prognosis was investigated in 195 cases. RESULTS: The expression of COX-2 mRNA in
      gastric cancer tissue was significantly higher than that in normal tissue in 47
      cases (w = 792, P<0.01). The COX-2 mRNA in pT3-4 tissue expressed higher than
      that in pT1-2 tissue (w = 204, P<0.05). The positive expression rate of COX-2
      protein was 57.9% (113/195). The COX-2 expression was significantly related to
      histological type, lymphnode metastasis, venous invasion and liver metastasis
      (P<0.05). No relation was found between COX-2 expression and invasion depth,
      peritoneal metastasis and International Union against Cancer TNM stage. The
      multiple regression analysis showed that the COX-2 expression and venous invasion
      were obviously associated with liver metastasis (P<0.05). However, there was no
      significant correlation between COX-2 immunoreactivity and prognosis. CONCLUSION:
      COX-2 may play an important role in the development of gastric cancer, and the
      over-expression of COX-2 protein may be a high risk factor for liver metastasis.

PMID- 16097071
TI  - Anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium-induced
      colitis of rats.
AB  - AIM: To investigate the anti-inflammatory mechanism of oxymatrine in dextran
      sulfate sodium (DSS)-induced colitis of rats. METHODS: Acute colitis was induced
      by giving 2% DSS orally in drinking water for 8 d. Twenty-six male rats were
      randomized into oxymatrine-treated group (group A, 10 rats), DSS control (group
      B, 10 rats) and normal control (group C, 6 rats). The rats in group A were
      injected muscularly with oxymatrine at the dosage of 63 mg/(kg.d) from d 1 to 11
      and drank 2% DSS solution from d 4 to 11. The rats in group B were treated with
      0.9% saline in an equal volume as group A and drank 2% DSS solution from d 4 to
      11. The rats in group C were treated with 0.9% saline as group B from d 1 to 11
      and drank water normally. Diarrhea and bloody stool as well as colonic histology
      were observed. The levels of serum tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) were determined by ELISA, and nuclear factor-kappaB (NF
      kappaB) activity and the expression of inter-cellular adhesion molecule-1 (ICAM
      1) in colonic mucosa were detected by immunohistochemistry method. RESULTS:
      Compared with DSS control group, the inflammatory symptoms and histological
      damages of colonic mucosa in oxymatrine-treated group were significantly
      improved, the serum levels of TNF-alpha, IL-6, and the expression of NF-kappaB,
      ICAM-1 in colonic mucosa were significantly reduced. CONCLUSION: The fact that
      oxymatrine can reduce the serum levels of TNF-alpha, IL-6, and the expression of
      NF-kappaB and ICAM-1 in colonic mucosa in DSS-induced colitis of rats indicates
      that oxymatrine may ameliorate the colonic inflammation and thus alleviate
      diarrhea and bloody stool.

PMID- 16097072
TI  - Expression of heparanase mRNA in anti-sense oligonucleotide-transfected human
      esophageal cancer EC9706 cells.
AB  - AIM: To investigate the effects of anti-sense oligonucleotides (ASODNs) on mRNA
      expression of heparanase in human esophageal cancer EC9706 cells. METHODS: One
      non-sense oligonucleotide (N-ODN) and five ASODNs against different heparanase
      mRNA sites were transfected into EC9706 cells, then the expression of heparanase
      mRNA in EC9706 cells was studied by in situ hybridization. RESULTS: The
      expression of heparanase mRNA could be inhibited by ASODNs. There was no
      significant difference among five ASODNs (P>0.05), but there was a significant
      difference between ASODNs and N-ODN or non-transfected group (ASODN1: 2.25+/
      0.25, ASODN2: 2.21+/-0.23, ASODN3: 2.23+/-0.23, ASODN4: 2.25+/-0.24 vs N-ODN:
      3.47+/-2.80 or non- transfected group: 3.51+/-2.93 respectively, P<0.05).
      CONCLUSION: The expression of heparanase mRNA in EC9706 cells can be inhibited by
      ASODNs in vivo, and heparanase ASODNs can inhibit metastasis of esophageal
      squamous cell carcinoma or other tumors by inhibiting the expression of
      heparanase.

PMID- 16097073
TI  - Increased expression of cyclooxygenase-2 in first-degree relatives of gastric
      cancer patients.
AB  - AIM: To study the expression of cyclooxygenase-2 (COX-2) in human gastric cancer
      tissues and their paired adjacent mucosa, as well as mucosa from gastric antrum
      and corpus of the first-degree relatives of the recruited cancer patients.
      METHODS: The expression of COX-2 mRNA in 38 patients with gastric cancer and
      their 29 first-degree relatives and 18 healthy controls was assessed by the real
      time RT-PCR. The expression of COX-2 protein was determined by Western blot.
      RESULTS: A marked increase in COX-2 mRNA expression was found in 20 of 37 (54%)
      cancerous tissues compared to their respective paired normal mucosa (P<0.001).
      Interestingly, increased COX-2 mRNA expression was also found in mucosa of the
      corpus (6/29) and antrum (13/29) of their first-degree relatives. Increased COX-2
      mRNA expression was more frequently observed in the antrum biopsies from cancer
      patients than in the antrum biopsies from healthy controls (P<0.05). In addition,
      3 of 23 (13%) patients with atrophic mucosa and 6 of 35 (17%) patients with
      intestinal metaplasia showed increased COX-2 mRNA expression. Furthermore, COX-2
      expression increased in H pylori-positive tissues, especially in antrum mucosa.
      CONCLUSION: Increased COX-2 expression is involved in gastric carcinogenesis, and
      may be necessary for maintenance of the malignant phenotype and contribute to
      Helicobacter pylori-associated malignant transformation.

PMID- 16097074
TI  - Klatskin tumor treated by inter-disciplinary therapies including stereotactic
      radiotherapy: a case report.
AB  - In view of the poor prognosis of patients with cholangiocarcinoma (CCC), there is
      a need for new therapeutic strategies. Inter-disciplinary therapy seems to be
      most promising. Radiotherapy is an effective alternative to surgery for hilar CCC
      (Klatskin tumors) if an adequate radiation dose can be delivered to the liver
      hilus. Here, we describe a patient for whom we used a stereotactic radiotherapy
      technique in the context of an inter-disciplinary treatment concept. We report a
      45-year-old patient with a locally advanced Klatskin tumor. Explorative
      laparotomy showed that the tumor was not resectable. A metallic stent was
      implanted and the patient was treated by stereotactic radiotherapy using a body
      frame. A total dose of 48 Gy (3X4 Gy/wk) was administered. Therapy was well
      tolerated. After 32 mo, local tumor recurrence and a chest wall metastasis
      developed and were controlled by radio-chemotherapy. After more than 56 mo with a
      good quality of life, the patient died of advanced neoplastic disease.
      Stereotactic radiotherapy led to a long-term survival of this patient with a
      locally advanced Klatskin tumor. In the context of inter-disciplinary treatment
      concepts, this radiotherapy technique is a promising choice of treatment for
      patients with hilar CCC.

PMID- 16097075
TI  - Calcified reticulate rind sign: a characteristic feature of gossypiboma on
      computed tomography.
AB  - We herein report a gossypiboma resulting from a retained surgical swab, which had
      been left in peritoneum for 20 years after appendectomy. CT revealed a cystic
      mass with a calcified reticulate rind. Subsequent surgery and pathological
      examination showed a gossypiboma. A simple experiment, using a barium-soaked
      surgical swab demonstrating similar CT appearance, supported our postulation that
      calcium deposition on the reticulated fibers of a surgical swab could generate
      such a characteristic "calcified reticulate rind" sign. We believe that
      identification of this CT sign facilitates the diagnosis of gossypibomas.

PMID- 16097076
TI  - Computed tomography diagnosis of tracheobronchopathia osteochondroplastica.
AB  - Tracheobronchopathia osteochondroplastica (TO) is a rare benign disease
      characterized by the presence of osseous and cartilaginous submucosal nodules
      projecting into the tracheobronchial tree. Most cases are asymptomatic and
      discovered incidentally at post-mortem. We identified a case of TO on thoracic
      spiral CT and confirmed the diagnosis of bronchoscopy. This article reviews the
      imaging characteristics of TO, and shows the 3-D virtual bronchoscopic and
      multiplanar reconstruction appearances of TO.

PMID- 16097077
TI  - Special issue dedicated to the memory of Murray Goodman.

PMID- 16097078
TI  - Do the right thing.

PMID- 16097079
TI  - Malcolm Ferguson-Smith.

PMID- 16097080
TI  - Abstracts of the International Continence Society 35th Annual Meeting, Montreal,
      Canada, 28 August-2 September 2005.

PMID- 16097081
TI  - Assignment of the bovine tumor protein D52 gene (TPD52) to the distal half of
      BTA14 with somatic and radiation cell hybrid panel mapping.

PMID- 16097082
TI  - Assignment of suppressor of cytokine signalling-2 (SOCS2) to porcine chromosome 5
      with radiation hybrids.

PMID- 16097083
TI  - Assignment of the calcium channel, voltage-dependent, P/Q type, alpha 1A subunit
      gene (CACNA1A), and the ataxin 7 gene (ATXN7) to canine chromosome 20 by
      fluorescence in situ hybridization  and confirmation by radiation hybrid mapping.

PMID- 16097084
TI  - Assignment of murine placental cathepsin R to mouse chromosome bands 13B2-B3 by
      fluorescence in situ hybridization.

PMID- 16097085
TI  - Assignment of the telomere-repeat binding factor genes TERF1 and TERF2 to Chinese
      muntjac (2n = 46) chromosome bands 12q3 and 2q33 by in situ hybridization.

PMID- 16097086
TI  - Abstracts of the British Society for Rheumatology annual meeting and the British
      Health Professionals spring meeting, April 2004, Edinburgh, Scotland.

PMID- 16097087
TI  - Remarks of the Acting FDA Commissioner: FDLI's 48th annual conference.

PMID- 16097088
TI  - Developments in food and drug law.

PMID- 16097089
TI  - Remarks at the Food and Drug Law Institute's 48th Annual Conference.

PMID- 16097090
TI  - Remarks delivered at the Food and Drug Law Institute's 48th Annual Conference.

PMID- 16097091
TI  - Drug regulation 2056.

PMID- 16097092
TI  - Challenges in regulating breakthrough medical devices.

PMID- 16097093
TI  - Effect of body position on feline electrocardiographic recordings.
AB  - The aim of this study was to determine whether changes in body position alter
      feline electrocardiographic parameters. Forty-seven cats referred to the Feline
      Unit of the University of Bristol had electrocardiograms (ECGs) recorded. Only
      cats presenting in sinus rhythm were included in the study (n = 41). ECGs were
      recorded either as part of the investigation for potential cardiac disease (n =
      38) or as a preanesthetic screen (n = 3). Standard 6-lead ECGs (leads I, II, III,
      aVR, aVL, and aVF) were recorded in 3 different recumbent positions in the 41
      cats. Recordings were 1st made in right lateral (RL) recumbency, followed by
      sternal (ST) and then left lateral (LL) recumbency. Measurements were taken of
      the amplitude and duration of P waves and QRS complexes and duration of PQ and QT
      intervals from lead II was taken in the 3 different positions. Mean electrical
      axis (MEA) also was calculated. Repeated measures analysis of variance was
      performed and identified a significant difference in R wave amplitudes (P = .009)
      and MEA (P = .037) among the 3 different body positions. Two-tailed paired t
      tests demonstrated that the R wave amplitude differed significantly both in ST (P
      = .025) and LL recumbency (P = .009). The mean R wave amplitude was reduced in
      both ST and LL recumbency when compared with RL recumbency. The MEA only was
      significantly different in LL recumbency (P = .037). ST and LL recumbencies
      should not be used for recording ECGs in cats if amplitudes and MEA are to be
      compared with standard references.

PMID- 16097094
TI  - [The 17th Spring meeting of the Japanese Society of Clinical Immunology. Okayama,
      Japan. June 2-4, 2005. Abstracts].

PMID- 16097095
TI  - Medicare program; changes to the hospital inpatient prospective payment systems
      and fiscal year 2006 rates. Final rule.
AB  - We are revising the Medicare hospital inpatient prospective payment systems
      (IPPS) for operating and capital-related costs to implement changes arising from
      our continuing experience with these systems. In addition, in the Addendum to
      this final rule, we describe the changes to the amounts and factors used to
      determine the rates for Medicare hospital inpatient services for operating costs
      and capital-related costs. We also are setting forth rate-of-increase limits as
      well as policy changes for hospitals and hospital units excluded from the IPPS
      that are paid in full or in part on a reasonable cost basis subject to these
      limits. These changes are applicable to discharges occurring on or after October
      1, 2005, with one exception: The changes relating to submittal of hospital wage
      data by a campus or campuses of a multicampus hospital system (that is, the
      changes to Sec. 412.230(d)(2) of the regulations) are effective on August 12,
      2005. Among the policy changes that we are making are changes relating to: The
      classification of cases to the diagnosis-related groups (DRGs); the long-term
      care (LTC)-DRGs and relative weights; the wage data, including the occupational
      mix data, used to compute the wage index; rebasing and revision of the hospital
      market basket; applications for new technologies and medical services add-on
      payments; policies governing postacute care transfers, payments to hospitals for
      the direct and indirect costs of graduate medical education, submission of
      hospital quality data, payment adjustment for low-volume hospitals, changes in
      the requirements for provider-based facilities; and changes in the requirements
      for critical access hospitals (CAHs).

PMID- 16097096
TI  - The role of new agents in the treatment of colorectal cancer.

PMID- 16097097
TI  - [Study in the novel function of adipose tissue on wound healing].

PMID- 16097098
TI  - [Sponsorship, authorship, and responsibility].

PMID- 16097099
TI  - How are community resources used in case management?

PMID- 16097100
TI  - How are community resources used in case management?

PMID- 16097101
TI  - Worker's compensation--essential functions of the job.

PMID- 16097102
TI  - Vulnerable worker populations--special issue.

PMID- 16097103
TI  - The youth work force: unique occupational health considerations and challenges.
AB  - During the past decade, the characteristics and number of adolescent workers has
      changed little. Several studies were conducted during this time documenting the
      patterns, scope, and effect of work among young individuals in the United States.
      Part-time employment may benefit youth by imparting positive work values,
      reinforcing the importance of academic skills for future career success,
      providing a better understanding of the workplace, increasing contact with
      adults, and building character. Negative aspects of youth employment include
      threats to completion of developmental tasks and education, injury, toxic
      exposure, and illness. The enactment of regulations and resulting change in the
      nature of youth employment has contributed to a substantial decrease in youth
      related occupational fatality and injury. However, youth workers continue to
      suffer fatal and nonfatal occupational injuries with most injuries occurring in
      the retail industry. Efforts should be made to develop innovative interventions
      tailored to young workers that focus on surveillance, advocacy, education, and
      research to decrease workplace injury and illness.

PMID- 16097104
TI  - Disabilities in the workplace: recruitment, accommodation, and retention.
AB  - Who has never had a need for accommodation to perform a job because of age
      related changes, gender issues related to family care, religious practices,
      health status, or disability? Who has never had the benefit of universal
      accommodations designed to provide access for individuals with disabilities, such
      as using the handicap button to open a door when one's arms are loaded? All of
      society has had the benefit of inclusion of individuals with disabilities within
      the work force. Occupational health nurses are essential to accommodating new
      employees with disabilities, assisting ill or injured employees in returning to
      work, and changing attitudes toward disabled workers. Additionally, nurses have
      the skills and knowledge for leading and managing newly emerging disease
      management programs for workers with disabilities caused by chronic illness.

PMID- 16097105
TI  - Immigrant workers in the United States: recent trends, vulnerable populations,
      and challenges for occupational health.
AB  - Immigrant workers are a rapidly growing segment of the U.S. work force, and these
      increasing numbers have resulted in a different ethnic mix in the work force than
      in previous decades. Immigrant workers are not a homogenous group, but are over
      represented in low-paying occupations. Their diversity and vulnerability present
      distinct challenges for occupational health nurses. High-risk occupations in
      which a large proportion of immigrant workers are hired include agriculture,
      sweatshops, day laborers, and construction. Initiatives needed to improve the
      working conditions of this vulnerable population include improved surveillance
      and research, culturally competent care providers, improved health care access,
      advocacy, and changes in immigration and health policy.

PMID- 16097106
TI  - The unique health needs of young women: application for occupational health
      professionals.
AB  - This article presents some alternate views on how young women maintain health and
      how occupational health nurses can intervene with illness. These interventions
      are based on relational theories that address the importance of healthy
      connections for health and growth, and propose disconnections as what (Miller &
      Stiver, 1977): underlies many of the problems common to women in particular,
      including depression, various forms of anxiety, eating problems, and so-called
      personality disorders." (p. 81) Interventions outlined include teaching young
      women and families how to deconstruct damaging media images and creating groups
      for young women or parents as a venue to learn (e.g., signs of healthy and
      unhealthy relationships and knowing how interaction in the group can be an
      intervention in itself). Offering parents and other adults support and resources
      to help them discuss health issues with young women will provide a way for young
      women to examine healthy choices more accurately. The occupational health nurse
      can teach the importance of keeping connected during an illness and refer clients
      to an EAP for additional support. Knowing that some young women do not have homes
      where they receive adequate safe and healthy messages reinforces the value of a
      nurse and managers to create a caring and respectful climate in the workplace.
      The effectiveness of applying relational theories to health care is evidenced
      when professionals offer young women a resonant relationship, with mutuality and
      respect which fosters a safe environment for voicing health concerns (Slater,
      Guthrie, & Boyd, 2001). Occupational health nurses can also make a difference for
      young women within their own communities. Whether taking social action in a town
      meeting, addressing media influences, writing a letter when offended, or
      supporting local and national girls' organizations, nurses' input is valuable.
      Interactions with girls outside the workplace are also important. Young women
      often consider relationships with the older women in their lives (e.g., mothers,
      aunts, parents for whom they babysit) to be among the most valuable. With
      cultural messages normalizing unhealthy behaviors and health consequences, young
      women can benefit greatly from their relationships with adult relatives and
      friends who care enough to stay connected.

PMID- 16097107
TI  - Supporting visually impaired adults in the workplace.

PMID- 16097108
TI  - Albumin and its role in trauma resuscitation.

PMID- 16097109
TI  - Gender differences in the cause of low back pain in British soldiers.
AB  - OBJECTIVES: To explore gender differences in the cause of low back pain in a
      population of military personnel who are expected to undertake high levels of
      sport, exercise and physical military training. METHODS: A prospective study of
      trained British soldiers, with symptomatic low back pain, referred to the
      Colchester Garrison Sports Injury and Rehabilitation Centre over a four year
      period. RESULTS: The study demonstrates that 928 (17.8%) of the 5214 referrals
      were for new cases of low back pain. The incidence of low back pain in female
      soldiers is higher than their male counterparts with an odds ratio of 3.17 (95%
      CI 2.31 - 4.35) There was a highly significant cross gender difference in low
      back pain caused by activities in the followining categories: military physical
      traininong (OR 2.65, 95% CI 1.70 - 4.02), work or occupation (OR 2.49, 95% CI
      1.56 - 3.87) and off-duty pursuits (OR 2.91, 95% CI 1.72 - 4.72). There was no
      cross gender difference in low back pain caused by sport, road traffic accidents
      or activities pre-dating military service. CONCLUSIONS: Female soldiers are
      significantly more likely to suffer low back pain as a result of physical
      military training, their occupation, or off-duty activities. Sporting activities
      do not cause low back pain in women to a greater extent than men By demonstrating
      the scale of the problem and by determining of the cause of injury, it should now
      be possible to propose methods of effective intervention to reduce injury,
      implement those interventions and audit effectiveness.

PMID- 16097110
TI  - Clinical guidelines for the management of cutaneous leishmaniasis in British
      military personnel.

PMID- 16097111
TI  - Early failure of external fixation in the management of war injuries.
AB  - OBJECTIVE: To review external fixation in the management of war injuries. METHOD:
      We prospectively followed up 15 external fixators (14 patients) applied in the
      management of war injuries. All these patients were treated at 202 Field Hospital
      during the 2003 Gulf Conflict. RESULTS: Of the 15 fixators, 13 (86.7%) required
      early revision or removal due to complications of the injury or the fixator.
      Instability was a problem with 10 fixators (67%), pin loosening was noted with 5
      fixators (33%) involving twelve pins, and a significant pin track infection
      developed at 14 pin sites (3 fixators - 20%), which failed to resolve despite
      intravenous antibiotics. CONCLUSIONS: This study demonstrates a very high early
      complication rate of external fixation in the management of military injuries and
      cautions against its universal acceptance. If used, consideration must be given
      to the optimum time of frame application, whether at the time of initial
      debridement or at a later operation, and the optimal frame design, which will
      depend on the specific bone and fracture pattern. Pin site care must also be
      considered, particularly with the restrictions imposed by the military
      environment.

PMID- 16097112
TI  - The management of head injuries on military operations.
AB  - The management of head injured patients has recently been reviewed with the
      development of civilian guidelines for best practice. These are common injuries
      which often have significant sequelae for patients and costs for health care
      providers. Evolving civilian standards of care have implications for military
      medicine which is often practised in challenging environments. Considerable
      planning and resources are necessary to meet these standards in an operational
      environment. The current standards and the problems of applying them in an
      operational theatre are discussed.

PMID- 16097113
TI  - An unusual case of segmental clavicle fracture.
AB  - Fracture of the clavicle is a common traumatic injury and comprises 4% of all
      fractures in adults. Amongst these, midshaft injuries account for the majority
      and medial fractures are uncommon. Whilst segmental fractures have been reported
      in the literature, concurrent lateral and medial injuries are very rare. These
      injuries are, therefore, susceptible to being missed, due to failure to look for
      a second injury after the initial diagnosis, and difficult X-ray interpretation
      around the area of the medial clavicle. The nature of segmental fractures can
      pose a difficult management problem for numerous reasons, and initial operative
      fixation is usually indicated. Early diagnosis is therefore imperative, and as
      such, clinical examination is essential even if an obvious mid or lateral shaft
      fracture is seen on X-ray. This unusual case of combined lateral and medial
      fractures was initially missed and the presentation and management is discussed.

PMID- 16097114
TI  - Diagnosis and outcome of psychiatric referrals to the Field Mental Health Team,
      202 Field Hospital, Op Telic I.
AB  - OBJECTIVES: To assess referrals to a Field Hospital Mental Health Team (FMHT),
      assign a diagnosis, provide appropriate treatment, and decide whether suitable
      for safe return to unit in theatre (RTU), or evacuation home on psychiatric
      grounds (evac). METHODS: All documented referrals to the FMHT of 202 Field
      Hospital during the Op Telic 1 study period of 17 March (day 1) to 23 July 2003
      (day 129) were included. Data were collected on rank, gender, diagnosis, outcome
      (whether RTU or evac), and whether TA before mobilisation. Diagnosis was assigned
      by ICD-10 criteria. RESULTS: The FMHT documented 170 cases, 12 of whom were seen
      twice and one on three occasions, resulting in 184 referrals, all of whom were
      British. The commonest diagnosis was adjustment reaction (F43), accounting for
      68% of all cases (n = 116). These were divided between chiefly theatre-related (n
      = 77) or chiefly home-related (n = 39) reactions. The majority (94%) of these
      cases were RTU. Referrals where the diagnosis was a Depressive disorder (F32, n =
      23) or Intentional self-harm (by sharp object, X78, n = 7) were evacuated.
      Outcome was similar for Regular and TA personnel, with on average 72% of cases
      RTU. The majority of cases seen were ORs, reflecting their numbers in theatre.
      Only 14 NCOs and 14 officers were referred. Thirteen of the latter were TA before
      mobilisation. Gender was not associated with outcome, or TA status, but was
      associated with rank, in that significantly more female officers were referred.
      The FMHT role tasks emerged as (a) psychiatric triage and treatment, (b)
      psychological support of hospital staff, and (c) welfare and pastoral care
      liaison. CONCLUSION: The utility of the psychiatric management model employed,
      built upon previous military medical doctrines, was tested in a modern theatre of
      conflict, and seemed to prove its worth.

PMID- 16097115
TI  - The role of the physician in modern military operations: 12 months experience in
      Southern Iraq.
AB  - OBJECTIVES: To examine the profile of medical morbidity and the role of the
      physician in modern conflict. METHODS: Retrospective survey of admission records
      at a British Military Field Hospital on operational duty in Southern Iraq.
      RESULTS: 62.5% of 4870 admissions to the Field Hospital in Shaibah during the
      first 12 months of military operations in Iraq were under the care of physicians.
      Of these 1531 (31.4%) were due to diarrhoea and vomiting (D&V) and 764 (15.7%)
      due to heat illness. The incidence of heat illness rose with ambient temperature,
      but soldiers were more likely to be admitted with heat illness shortly after
      arrival in theatre than when fully acclimatised. There was also a steady flow of
      admissions with a broad spectrum of medical pathology requiring the clinical
      skills of a general physician. CONCLUSIONS: A general physician is a necessary
      part of the clinical team in modern conflict. The incidence of D&V and of heat
      illness on military operations remains high. Planners for any operation in
      tropical climates should take this into consideration and put preventative
      measures into place early.

PMID- 16097116
TI  - Marie Curie's other role.

PMID- 16097117
TI  - On the value of beta eucain and adrenalin as a local analgesic in military
      surgery. 1907.

PMID- 16097118
TI  - Paediatric casualties during OP TELIC.

PMID- 16097119
TI  - How does your coding measure up? Analyzing performance data gives HIM a boost in
      managing revenue.

PMID- 16097120
TI  - The codes to watch: identifying the DRGs most prone to payment error.

PMID- 16097121
TI  - Data abstraction unplugged. Taking trauma registry to the point of care with
      wireless technology.

PMID- 16097122
TI  - Transcription's future(s). AAMT and AHIMA outline scenarios for the years ahead.

PMID- 16097123
TI  - Destroying data the DoD way.

PMID- 16097124
TI  - Stamp of approval. Getting EHR wheels turning with product certification.

PMID- 16097125
TI  - Amending business associate contracts. Harmonizing privacy and security for
      protected health information.

PMID- 16097126
TI  - Coordinating SNOMED-CT and ICD-10.

PMID- 16097127
TI  - Practice brief. The role of the personal health record in the EHR.

PMID- 16097128
TI  - Problem list coding in e-HIM.

PMID- 16097129
TI  - Coding connections in revenue cycle management.

PMID- 16097130
TI  - A passion for coding.

PMID- 16097132
TI  - Living and leaving your nursing legacy.

PMID- 16097133
TI  - Career mentoring works.

PMID- 16097134
TI  - What every nurse should know about professional liability insurance.

PMID- 16097135
TI  - What's happening in gerontological nursing!

PMID- 16097136
TI  - Carcinogenicity studies of diesel engine exhausts in laboratory animals: a review
      of past studies and a discussion of future research needs.
AB  - Diesel engines play a vital role in world economy, especially in transportation.
      Exhaust from traditional diesel engines using high-sulfur fuel contains high
      concentrations of respirable carbonaceous particles with absorbed organic
      compounds. Recognition that some of these compounds are mutagenic has raised
      concern for the cancer-causing potential of diesel exhaust exposure. Extensive
      research addressing this issue has been conducted during the last three decades.
      This critical review is offered to facilitate an updated assessment of the
      carcinogenicity of diesel exhaust and to provide a rationale for future animal
      research of new diesel technology. Life-span bioassays in rats, mice, and Syrian
      hamsters demonstrated that chronic inhalation of high concentrations of diesel
      exhaust caused lung tumors in rats but not in mice or Syrian hamsters. In 1989,
      the International Agency for Research on Cancer (IARC) characterized the rat
      findings as "sufficient evidence of animal carcinogenicity," and, with "limited"
      evidence from epidemiological studies, classified diesel exhaust Category 2A, a
      "probable human carcinogen." Subsequent research has shown that similar chronic
      high concentration exposure to particulate matter generally considered innocuous
      (such as carbon black and titanium dioxide) also caused lung tumors in rats.
      Thus, in 2002, the U.S. Environmental Protection Agency (EPA) concluded that the
      findings in the rats should not be used to characterize the cancer hazard or
      quantify the cancer risk of diesel exhaust. Concurrent with the conduct of the
      health effects studies, progressively more stringent standards have been
      promulgated for diesel exhaust particles and NOx. Engine manufacturers have
      responded with new technology diesel (improved engines, fuel injection, fuels,
      lubricants, and exhaust treatments) to meet the standards. This review concludes
      with an outline of research to evaluate the health effects of the new technology,
      research that is consistent with recommendations included in the U.S. EPA 2002
      health assessment document. When this research has been completed, it will be
      appropriate for IARC to evaluate the potential cancer hazard of the new
      technology diesel.

PMID- 16097137
TI  - Evaluation of physiologically based pharmacokinetic models in risk assessment: an
      example with perchloroethylene.
AB  - One of the more problematic aspects of the application of physiologically based
      pharmacokinetic (PBPK) models in risk assessment is the question of whether the
      model has been adequately validated to provide confidence in the dose metrics
      calculated with it. A number of PBPK models have been developed for
      perchloroethylene (PCE), differing primarily in the parameters estimated for
      metabolism. All of the models provide reasonably accurate simulations of selected
      kinetic data for PCE in mice and humans and could thus be considered to be
      "validated" to some extent. However, quantitative estimates of PCE cancer risk
      are critically dependent on the prediction of the rate of metabolism at low
      environmental exposures. Recent data on the urinary excretion of trichloroacetic
      acid (TCA), the major metabolite of PCE, for human subjects exposed to lower
      concentrations than those used in previous studies, make it possible to compare
      the high- to low-dose extrapolation capability of the various published human
      models. The model of Gearhart et al., which is the only model to include a
      description of TCA kinetics, provided the closest predictions of the urinary
      excretion observed in these low-concentration exposures. Other models
      overestimated metabolite excretion in this study by 5- to 15-fold. A systematic
      discrepancy between model predictions and experimental data for the time course
      of the urinary excretion of TCA suggested a contribution from TCA formed by
      metabolism of PCE in the kidney and excreted directly into the urine. A
      modification of the model of Gearhart et al. to include metabolism of PCE to TCA
      in the kidney at 10% of the capacity of the liver, with direct excretion of the
      TCA formed in the kidney into the urine, markedly improved agreement with the
      experimental time-course data, without altering predictions of liver metabolism.
      This case study with PCE demonstrates the danger of relying on parent chemical
      kinetic data to validate a model that will be used for the prediction of
      metabolism.

PMID- 16097138
TI  - A review of the endocrine activity of parabens and implications for potential
      risks to human health.
AB  - Parabens are a group of the alkyl esters of p-hydroxybenzoic acid and typically
      include methylparaben, ethylparaben, propylparaben, butylparaben,
      isobutylparaben, isopropylparaben, and benzylparaben. Parabens (or their salts)
      are widely used as preservatives in cosmetics, toiletries, and pharmaceuticals
      due to their relatively low toxicity profile and a long history of safe use.
      Testing of parabens has revealed to varying degrees that individual paraben
      compounds have weakly estrogenic activity in some in vitro screening tests, such
      as ligand binding to the estrogen receptor, regulation of CAT gene expression,
      and proliferation of MCF-7 cells. Reported in vivo effects include increased
      uterine weight (i.e., butyl-, isobutyl-, and benzylparaben) and male reproductive
      tract effects (i.e., butyl- and propylparaben). However, in relation to estrogen
      as a control during in vivo studies, the parabens with activity are many orders
      of magnitude less active than estrogen. While exposure to sufficient doses of
      exogenous estrogen can increase the risk of certain adverse effects, the
      presumption that similar risks might also result from exposure to endocrine
      active chemicals (EACs) with far weaker activity is still speculative. In
      assessing the likelihood that exposure to weakly active EACs might be
      etiologically associated with adverse effects due to an endocrine-mediated mode
      of action, it is paramount to consider both the doses and the potency of such
      compounds in comparison with estrogen. In this review, a comparative approach
      involving both dose and potency is used to assess whether in utero or adult
      exposure to parabens might be associated with adverse effects mediated via an
      estrogen-modulating mode of action. In utilizing this approach, the paraben doses
      required to produce estrogenic effects in vivo are compared with the doses of
      either 17beta-estradiol or diethylstilbestrol (DES) that are well established in
      their ability to affect endocrine activity. Where possible and appropriate,
      emphasis is placed on direct comparisons with human data with either 17beta
      estradiol or DES, since this does not require extrapolation from animal data with
      the uncertainties inherent in such comparisons. Based on these comparisons using
      worst-case assumptions pertaining to total daily exposures to parabens and
      dose/potency comparisons with both human and animal no-observed-effect levels
      (NOELs) and lowest-observed-effect levels (LOELs) for estrogen or DES, it is
      biologically implausible that parabens could increase the risk of any estrogen
      mediated endpoint, including effects on the male reproductive tract or breast
      cancer. Additional analysis based on the concept of a hygiene-based margin of
      safety (HBMOS), a comparative approach for assessing the estrogen activities of
      weakly active EACs, demonstrates that worst-case daily exposure to parabens would
      present substantially less risk relative to exposure to naturally occurring EACs
      in the diet such as the phytoestrogen daidzein.

PMID- 16097139
TI  - Comments on "Respiratory effects of toluene diisocyanate in the workplace: a
      discussion of exposure-response relationships".

PMID- 16097140
TI  - [Is tumour grade applicable to finasteride-treated prostate cancer?].
AB  - The treatment of prostate cancer by endocrine therapy induces histological
      changes of benign or malignant prostate glands. Treated cancers often have a more
      suspicious architecture, resulting in a higher Gleason score, while their nuclear
      grade (WHO) appears to be more reliable due to a reduction of the size of nuclei.
      Most authors appear to agree that cancers discovered by biopsy in patients
      treated with endocrine therapy should not be graded. A review of the literature
      appears to indicate that finasteride has less marked histomorphological
      consequences than other hormone-suppressor treatments and could have a lesser
      effect on the Gleason score. This paper, based on a review of the literature on
      this subject, emphasizes: (1) the extent of histological changes after androgen
      deprivation endocrine therapy; (2) histological changes after Finasteride and the
      difficulties of histological interpretation, particularly the risk of
      overestimating the Gleason histoprognostic score; (3) the need for urologists to
      indicate any treatment by 5-alpha-reductase inhibitors or androgen deprivation
      when requesting histological examination; (4) the value of collecting and
      documenting cases observed in the Uropathology Club in collaboration with the
      Oncology committee of the Association Francaise d'Urologie.

PMID- 16097141
TI  - [Management of priapism in patients with sickle-cell anaemia].
AB  - Sickle-cell anaemia is an autosomal recessive hereditary haemoglobinopathy.
      Patients with sickle-cell anaemia present a high risk of priapism. At least 40%
      of sickle-cell patients report episodes of priapism. Priapism in patients with
      sickle-cell tend to start during childhood and rapidly threaten the erectile
      prognosis. Apart from specific treatment of sickle-cell anaemia, the urologist
      must be able to recognize forms of intermittent priapism and promote medical
      prevention. The urologist must also be able to distinguish low-flow priapism from
      the rarer high-flow priapism, as the treatments differ. Treatment strategies are
      increasingly well defined, with an increasingly limited place for surgery.

PMID- 16097142
TI  - [Current place of chemotherapy in the treatment of hormone-refractory metastatic
      prostate cancer].
AB  - The current management of hormone-refractory metastatic prostate cancer is purely
      palliative. The use of chemotherapy in this indication was revised in 1996, based
      on the results of studies with a combination of mitoxantrone and prednisone. This
      combination demonstrated a significant improvement of quality of life (+48%) and
      pain (+30%), but without any overall survival benefit. Two studies using taxols,
      TAX_327 and SWOG_9916, were published in the New England Journal of Medicine on 7
      October 2004, with, for the first time, a median overall survival benefit of 2
      months. However, the encouraging results of these 2 studies, which will probably
      modify the management of hormone-refractory prostate cancer, need to be
      interpreted cautiously. First of all, they were conducted in selected study
      populations (mean age less than 70 years, Kamofsky index greater than 80% in more
      than 85% of cases, local disease control in more than 70% of cases). They also
      comprise many methodological imprecisions and biases with especially, in the TAX
      327 study, a change of treatment arm in 1/3 of patients without exclusion of
      these patients from the final analysis. The results obtained are also at the
      limit of statistical significance. The target improvement of overall survival,
      +25% and +33%, respectively, was not achieved at the end of these studies.
      Finally, from a palliative point of view, only one of these 2 studies (TAX_327)
      demonstrated a palliative benefit compared to mitoxantrone: 9% for pain, for a
      sixfold higher cost. Adverse effects were significantly more frequent than with
      mitoxantrone. Patient selection and details about the indications are necessary.
      Taxols should not be used systematically in this indication. Furthermore,
      although several studies are underway, the benefit of taxols at earlier stages of
      the disease are unknown. Urologists must be aware of the place of chemotherapy in
      the treatment of prostate cancer in order to remain at the centre of the
      treatment decision.

PMID- 16097143
TI  - [Small intestinal submucosa (SIS): prospects in urogenital surgery].
AB  - SIS (Small Intestinal Submucosa) is an extracellular matrix isolated from pig
      intestine. Since its discovery in 1987, many studies have defined its structure
      and have demonstrated its useful biointegration and tissue regeneration
      properties. It also appears to be a resistant substrate associated with a low
      risk of infection. The role of this matrix is still under investigation in many
      fields of surgery, but its value has been clearly established in urological and
      gynaecological surgery. Several experimental and clinical studies have reported
      interesting results in cystoplasties, repair of stress urinary incontinence by
      suburethral support, urethroplasties or even chordee of the penis. Applications
      of this material are still to be evaluated in pelvic floor disorders,
      particularly in prolapse surgery.

PMID- 16097144
TI  - [Value of infrared spectrophotometry morpho-constitutional analysis of double J
      stent encrustations for indirect determination of urinary stone composition].
AB  - INTRODUCTION: A single stone analysis is necessary during the patient's clinical
      history in order to institute specific drug treatment and health and dietary
      measures to prevent stone recurrence. In practice, only one in every two stones
      is recovered for morpho-constitutional analysis. The objective of this study was
      to determine the place of double J stent encrustation analysis for indirect
      determination of stone composition. MATERIAL AND METHODS: Double J stents and
      stones from all patients treated in the same centre over 24 months were
      consecutively analysed by infrared spectrophotometry. The correlation coefficient
      1, evaluating the concordance between the composition of stones and double J
      stent encrustation was estimated statistically by SPSS 12.0 software (0<1<1; 1=0:
      no concordance; 1=1: perfect concordance). RESULTS: 45 males and 27 females with
      a mean age of 45.3 years (range: 29-70) were included Double J stents were placed
      for: febrile obstruction (N=52; 72%), acute renal colic (N=15; 21%) and impaired
      renal function (N=5; 7%). Calculated values for 1 were: 0.78 for the concordance
      between the predominant constituent of the stone and the encrustation (N=72; p <
      0.0005); 0.91 for the concordance between the nature of the encrustation of the
      upper loop and that of the lower loop of the stent (N=30, p < 0.0005).
      CONCLUSION: The composition of mineral encrustation of double J stents is a good
      marker of stone formation. This constitutes an alternative method that can be
      used by urologists when no stone is available for spectrophotometric analysis.

PMID- 16097145
TI  - [Types and mechanisms of 54 cases of kidney trauma in car drivers injured by road
      accident].
AB  - PURPOSE: To analyse the types, mechanisms and severity of kidney trauma in
      injured car drivers and the effects of the presence or absence of the safety belt
      on the renal lesions observed. MATERIAL AND METHODS: 64,325 road accident victims
      were reported between 1996 and 2002. Data collection was performed in 96 primary
      care departments, 160 inpatient departments and 11 convalescence centres. Among
      the 33,431 injured car drivers, 54 presented kidney trauma (0.16%). The AAST
      classification was used to analyse these cases of RESULTS: The 54 cases of kidney
      trauma was classified as grade I and II in 39 cases, grade III in 6 cases, grade
      IV in 5 case, and grade V in 4 cases. Nine patients died with a kidney lesion.
      This lesion was never isolated, as it was associated with rupture of the spleen
      in 8 cases, head injury in 6 cases and chest injury in 4 cases. The mechanism of
      these fatal accidents was a head-on collision in every case. CONCLUSION: Kidney
      trauma in the car drivers of our series was rare (0.160%) and benign (72% of
      grade I and II lesions). Patients with a kidney lesion who died always presented
      multiple injuries. Renal pedicle lesions are usually observed in car drivers not
      wearing a

PMID- 16097146
TI  - [Study of crystalluria in diabetic patients].
AB  - INTRODUCTION: The incidence of diabetes, particularly non-insulin-dependent
      diabetes, is on the increase in industrialized and developing countries. The
      prevalence of renal stones in the diabetic population was recently estimated to
      be 21%, i.e. more than twice the prevalence of stones in the general population.
      Other studies have emphasized the high frequency of uric acid stones in this
      particular population. The present study was designed to verify whether diabetic
      patients present a particular type of crystalluria predisposing them to a high
      frequency of uric acid stones than other types of stones, which could allow
      detection of this risk and the proposal of therapeutic measures to prevent these
      stones. MATERIAL AND METHOD: The first morning urine of 208 diabetic patients was
      examined by polarized light microscopy to detect and identify crystalluria.
      Patients were distributed into 3 age-groups: less than 40 years, 40 to 59.9 years
      and 60 years or more. The results are expressed as the predominant crystalline
      species. RESULTS: The overall frequency of crystalluria was 29.8%, i.e. about one
      half that observed in calcium stones. However, the crystallogenic profile was
      very unusual, as 61.3% of cases of crystalluria consisted of purine. Uric acid
      crystalluria was twice as frequent in women than in men (66% vs 33.3%, p < 0.05).
      The mean pH of the urine of diabetic subjects was 5.5, i.e. significantly more
      acidic than that of normal subjects or patients with calcium stones. pH was
      negatively correlated with the patient's age, decreasing from 5.54 in patients
      younger than 40 to 5.3 in patients over the age of 60 (p < 0.05). The mean pH of
      crystalluric urine was significantly more acidic than that of crystal-free urine
      (pH 5.2 +/- 0.46 vs 5.5 +/- 0.67, p < 0.01). CONCLUSION: Diabetic patients have
      an acidic urinary pH which tends to decrease with age, predisposing to uric acid
      crystalluria, which is particularly frequent in women. The high prevalence of
      uric acid crystalluria and the high proportion of uric acid stones reported in
      diabetic women suggest that women are at greater risk than men of developing uric
      acid stones in the context of diabetes. The study of crystalluria could be useful
      to detect this risk and to propose preventive measures. Complementary studies are
      necessary to identify factors accounting for the increased risk of uric acid
      stones in diabetic women and to verify whether good glycaemic control can reduce
      the crystallogenic risk.

PMID- 16097147
TI  - [Prostatic biopsy technique in the Centre region].
AB  - Prostate cancer is the most frequent cancer and second cause of cancer mortality
      in men. The objective of this study was to analyse the prostatic biopsy technique
      and to verify its conformity with the reference technique of the Centre region.
      MATERIAL AND METHOD: This study concerned first-line biopsies performed and
      analysed between 01/01/2001 and 31/03/2001 by all pathologists of the Centre
      region. We analysed the anaesthesia used to perform these biopsies, whether or
      not the patient was hospitalized, the needle diameter, the use of ultrasound or
      finger guidance, the operator's specialization and whether he/she worked in the
      private or public sector, the number of biopsies, the histology request form and
      the antibiotic prophylaxis used. RESULTS: Six hundred and twelve reports were
      sent by laboratories at the request of the regional health insurance fund. There
      were 562 first-line biopsies, which represented 93% of all biopsies studied
      Biopsy was performed as an outpatient procedure, the recommended modality, in
      only 36% of cases; in 10% of cases, hospitalization was justified by a particular
      clinical context. 11% of biopsies were not ultrasound-guided, particularly in the
      private sector. Information about histological type, Gleason grade, tumour
      volume, number of cores invaded and extension to the periprostatic space was
      present in 46% of cases. CONCLUSIONS: Only 40% of biopsies performed during the
      first quarter of 2001 complied with recognized quality criteria: ultrasound
      guidance, as an outpatient procedure or justified hospitalization, without
      anaesthesia or with local anaesthesia. Improvement of clinical practice probably
      requires a phase of discussions and negotiations between professionals and
      authorities to determine a reasonable fee allowing an objective choice adapted to
      the patient's state of health. The quality of the histological report is not
      satisfactory at the present time. A standard report was presented by the Reseau
      Regional de Cancerologie du Centre (Centre Regional Oncology Network) but has not
      been adopted by all professionals; further discussions are required to develop a
      simplified grid comprising essential information, especially as the quality of
      these reports determines treatment decisions.

PMID- 16097148
TI  - [Theoretical, practical, and assessment modalities of urology teaching during the
      second cycle of medical training in France].
AB  - INTRODUCTION: To comply with current legislation, French medical schools organize
      theoretical speciality teaching for medical students in speciality poles or in
      global modules. The objective of this study was to assess the theoretical,
      practical and assessment modalities of Urology teaching based on a survey.
      METHODS: In January 2004, a four-part questionnaire was sent to all urology
      teachers in 45 French universities. These 4 parts concerned: modalities of
      theoretical teaching, modalities of practical teaching, assessment modalities,
      evaluation of teaching, each evaluated by several questions. RESULTS: The
      response rate was 64.4% (29/45). Twelve medical schools chose teaching by
      speciality poles and 15 chose modular teaching. CCAs (Senior Registrars) played a
      greater role in modular teaching than in speciality pole teaching (75% and 53.3%
      of medical schools). Among the 12 medical schools with a speciality pole
      organization, 7 provided integrated teaching. An average of 23% of students of
      any one year receive Urology teaching during their training. Most medical schools
      conduct evaluation of theoretical (82.7%) and practical teaching (65.5%).
      CONCLUSION: Speciality teaching can be performed according to a polar or modular
      organization. A modular organization would be theoretically more appropriate to
      achieve the objective of a global approach to medicine, but artificial grouping
      of diseases can sometimes complicate speciality teaching in a speciality as
      diverse as Urology.

PMID- 16097149
TI  - [Double kidney transplantation].
AB  - The incidence of end-stage renal failure has been increasing for many years with
      a marked elevation of the mean age of kidney transplantation candidates. This
      situation contrasts with the shortage of kidney transplants. One solution, apart
      from the development of live donor kidney transplantation, is the use of so
      called "borderline" cadavre kidneys. Double kidney transplantation is performed
      in the context of enlargement of the number of "borderline" donors. A review of
      the medical literature reporting the experience acquired in double kidney
      transplantation demonstrates a marked heterogeneity of donor selection criteria
      between the various teams. Recipients are generally selected from among the
      oldest patients waiting for transplantation. Double kidney transplantation is not
      associated with any excess mortality and graft survival and graft function are
      perfectly satisfactory, ensuring a serum creatinine close to 200 micromol/l at 3
      years. These results are obtained at the price of low morbidity. Wound
      complications are not more frequent than after single kidney transplantation.
      With the exception of one team, vascular complications are not more frequent, but
      are even more serious than for single kidney transplantation. Ureteric strictures
      and fistulas are observed more frequently when the two ureters are reimplanted
      into a common conduit in the case of homolateral transplantation of the two
      kidneys. Overall, double kidney transplantation has allowed a 10% increase in the
      recruitment of "borderline" kidneys by all teams with satisfactory functional
      results and low morbidity. However, donor and recipient selection criteria for
      double kidney transplantation need to be more precisely defined to avoid
      depriving elderly patients of transplantation and to avoid using two kidneys in
      the same recipient when one kidney would have ensured a satisfactory functional
      result, Two ongoing French studies will probably allow progress in this direction
      by evaluating the feasibility and benefits of this technique in France.

PMID- 16097150
TI  - [Erectile dysfunction in renal failure patients and renal transplant recipients].
AB  - The frequency of erectile dysfunction can be increased in certain populations,
      such as patients with renal failure in whom the incidence of erectile dysfunction
      is estimated to be between 50% to 70% depending on the stage of renal failure. In
      this population, even more than in the general population, erectile dysfunction
      appears to be due to multiple aetiologies, combining organic and psychological
      disorders. Although renal transplantation is the treatment of choice for end
      stage renal failure, it appears to have very variable effects on erectile
      dysfunction, as it may improve erectile dysfunction in the same way as global
      quality of life. However, some authors have demonstrated the aggravating role of
      renal transplantation on quality of erection, or even de novo appearance of
      erectile dysfunction. Progress in the fields of dialysis and renal
      transplantation have considerably improved the quality of life of patients with
      chronic renal failure. However, this improvement of quality of life does not
      always concern the patient's sex life. The main causes of erectile dysfunction in
      haemodialysed patients are endocrine disorders, uraemic neuropathy, tissue
      lesions related to chronic renal failure, and drugs. These factors of erectile
      dysfunction are partially corrected by transplantation, but other factors can
      subsequently be involved, such as drugs or vascular causes. The objective of this
      study is therefore to conduct a review of the literature on erectile dysfunction
      (epidemiology, pathophysiology, treatment) in patients with end-stage renal
      failure (dialysis) and after renal transplantation.

PMID- 16097151
TI  - [Reduction of the renal transplantation cold ischaemia time by the use of a
      timesheet].
AB  - OBJECTIVE: Reduction of the cold ischaemia time is one of the major objectives
      designed to improve the quality and cost of renal transplantation. Based on the
      experience of other centres, we report the impact of using a renal
      transplantation timesheet on the cold ischaemia time in our centre. MATERIAL AND
      METHOD: Since March 2004, we have used a renal transplantation timesheet with the
      collaboration of all personnel involved in transplantation (coordination,
      nephrologists, clinical pathologists). For each kidney harvested, the name of the
      personnel and the start and end times of their interventions were recorded. The
      authors report the results for the first 7 months. Cold ischaemia times and the
      incidence of delayed graft function were studied. RESULTS: 47 kidneys were
      harvested between 01/03/2004 and 30/9/2004 in our centre and 46 transplantations
      were performed. The mean cold ischaemia time was 14 h 51 min, i.e. a reduction of
      8 hours 58 minutes compared to that observed in 2003 (23 h 50 min) (p < 0.01).
      Delayed graft function (DGF) was observed in 10/46 (21.74%) recipients. This DGF
      rate was significantly lower than that observed in 2003 (DGF 2003 = 30%), while
      the mean donor serum creatinine was higher (155 +/- 177 micromol/l vs 98 +/- 71
      micromol/l in 2003, p < 0.05). The longest delays were those related to
      availability of an operating room (n=2: 10 h and 14 h). CONCLUSION: The use of a
      renal transplantation timesheet allowed a significant reduction of the cold
      ischaemia time and DGF rate. It requires the collaboration of all renal
      transplantation personnel and is an indicator of motivation. This timesheet
      allowed the correction of certain habits that can still be improved. These
      results should lead to an improvement of the results and cost of renal
      transplantation.

PMID- 16097152
TI  - [Predisposing factors for ureteric strictures in renal transplantation].
AB  - OBJECTIVE: Renal transplantation is a well defined surgical procedure, but it
      nevertheless remains associated with a risk of medical and surgical
      complications. Ureteric strictures, with an incidence ranging from 2% to 7.5%
      according to the series, are the most frequent urological complication. The
      objective of this study was to determine the incidence of ureteric strictures and
      the existence of risk factors predisposing to the development of ureteric
      strictures and to evaluate their consequences on patient and graft survival,
      based on a single-centre retrospective series of renal transplantations. PATIENTS
      AND METHODS: From January 1990 to December 2002, 1787 renal transplantations were
      performed consecutively in our centre. Graft, donor and recipient characteristics
      were extracted from a computerized database and validated by an independent
      observer. The parameters studied included donor's age and recipient's age,
      donor's haemodynamic status and serum creatinine at the time of harvesting, cause
      of death, graft weight and number of graft arteries, cold ischaemia and
      reperfusion times, number of HLA incompatibilities and percentage anti-HLA
      immunization, time to return of graft function, acute rejection, presence or
      absence of a double J stent, episodes of acute pyelonephritis, CMV infection and
      patient and graft survival according to the Kaplan-Meier method. RESULTS:
      Ureteric stricture was observed in 74 patients (4.1% of cases) and a donor age
      greater than 65 years (p < 0.0001), the presence of more than 2 arteries on the
      graft (p = 0.03) and recipients with an anti-HLA immunization less than 25% (p =
      0.037) were identified as independent risk factors. Furthermore, grafts
      complicated by ureteric stricture resumed function later (p = 0.001). The
      development of ureteric stricture did not have an unfavourable impact on the 10
      year recipient and graft survival rates.

PMID- 16097153
TI  - [Therapeutic management of ureteric strictures in renal transplantation].
AB  - OBJECTIVE: Ureteric strictures, with a reported incidence ranging from 2% to
      7.5%, are the most frequent urological complication of renal transplantation.
      This article reports the results of open surgery and percutaneous or endoscopic
      techniques used to treat these strictures, based on a single-centre retrospective
      series of renal transplantations. PATIENTS AND METHODS: From January 1990 to
      December 2002, in a series of 1787 consecutive renal transplantations performed
      in our centre, 74 were complicated by ureteric stricture (4.1% of cases).
      Strictures occurred at the ureterovesical implantation in 82.4% of cases and
      during the first year in 88% of cases. The mean time to management of the
      stricture after transplantation was 9 months (range: 6 days-120 months). Criteria
      of success were defined by regression or even resolution of ultrasound signs of
      dilatation associated with stabilization of serum creatinine obtained by the
      external urinary diversion. Surgical or percutaneous revisions (particularly
      repeated changes of double J stents) were considered to be treatment failures.
      RESULTS: 44 strictures (59.5% of cases) were treated by open surgery and 30
      (40.5%) were treated by a first-line endoscopic or percutaneous technique. In our
      hands, open surgical techniques (ureteropelvic anastomosis: 80% of success (n=5),
      ureterovesical reimplantation: 82% of success (n=11), ureteroureteric
      anastomosis: 100% of success (n=4)) gave better results than endourological
      techniques (endoscopic electrical incision: 61.5% of success (n=13), double J
      stent: 61.5% of success (n=13), balloon catheter dilatation: no success (n=4)).
      CONCLUSION: Classical open surgical revision remains the reference treatment for
      ureteric strictures in renal transplantation for our team.

PMID- 16097154
TI  - [Evaluation of IGL-1, a new organ preservation solution: preclinical results in
      renal transplantation].
AB  - INTRODUCTION: Renal ischaemia and reperfusion lesions partly determine short-term
      and long-term graft survival. Organ preservation conditions appear to play a
      decisive role. This article presents the preclinical experimental results
      obtained in renal transplantation with an extracellular organ preservation
      solution, in which polyethylene glycol (PEG) is used as colloid. METHODS AND
      RESULTS: The effects of inversion of Na+ and K+ gradients in the IGL-1
      preservation solution compared to UW and replacement of hydroxylethyl starch
      (HES) by PEG were evaluated in an ex vivo isolated, perfused rat kidney model and
      then in a pig renal autotransplantation model. In these experimental models,
      after 24 hours of static storage, the sodium reabsorption fraction correlated
      with the quality of tubular function of the kidney and the glomerular filtration
      rate were constantly better in the IGL-1 group than in the UW group. In vivo, in
      the pig, resumption of renal function was significantly better in the IGL-1 group
      and histological examination demonstrated a significant reduction of expression
      of Major Histocompatibility Complex (MHC) type II, an indirect marker of
      inflammation, but also a reduction of markers of apoptosis and fibrosis for
      kidneys preserved in IGL-1. CONCLUSION: In animal renal transplantation, IGL-1
      ensures better resumption of renal function than UW, which currently remains the
      "gold standard"preservation solution. Further studies must be conducted to
      determine whether this new generation solution can replace UW as the reference
      solution.

PMID- 16097155
TI  - [Artificial urinary sphincters in women: indications, techniques, results].
AB  - Artificial urinary sphincter (AUS) is one of the last resort surgical treatments
      proposed to patients with stress urinary incontinence (SUI) due to severe
      sphincter incompetence. Despite convincing functional results, AUS implantation
      in women is a preferred treatment option only for certain teams. An abdominal
      approach for implantation of the prosthesis is often preferred to the
      transvaginal approach. The most recent data show that more than 84% of patients
      are continent at 5 years. The 5-year sphincter revision rate is about 20%. In
      2005, AUS is still a valid treatment option in SUI and has a real place in the
      urologist's therapeutic armamentarium even in the age of synthetic suburethral
      tape.

PMID- 16097156
TI  - [Intraurethral injections of Zuidex: evaluation of the morbidity of the technique
      in the treatment of female urinary incontinence].
AB  - OBJECTIVE: To evaluate the feasibility and morbidity of intraurethral injections
      of dextranomer/hyaluronic acid (Zuidex), performed under local anaesthesia as an
      outpatient procedure in the treatment of female urinary incontinence. MATERIAL
      AND METHODS: Twenty one patients with a mean age of 67 years (range: 29-93 years)
      presenting urinary incontinence related to sphincter incompetence were treated by
      intraurethral injection of Zuidex. Injections were performed with the Implacer
      system provided with the product under local anaesthesia. RESULTS: For nine of
      these patients (43%), a second injection after 6 weeks was performed due to an
      insufficient result on incontinence. A total of 30 injections were therefore
      performed. No significant problem was observed during the injections. Three
      injections (10%) were difficult because of a short urethra. In 7 cases (23%), the
      patient reported pain during the injection. In 3 cases (10%), macroscopic
      haematuria was observed after treatment and another 4 cases (13%) developed lower
      urinary tract infection. Six patients (20%) developed transient acute urinary
      retention with resumption of micturition after 24 to 48 hours. CONCLUSION:
      Intraurethral injection of Zuidex has the advantage of being minimally invasive
      and can be performed under local anaesthesia, as an outpatient procedure, with
      good safety and a low complication rate. Resumption of spontaneous voiding must
      be monitored in view of the risk of urinary retention. The long-term results have
      not yet been evaluated.

PMID- 16097157
TI  - [Clinicopathological correlation in bladder endometriosis].
AB  - Bladder endometriosis is a rare site of a disease with very polymorphic clinical
      signs. The authors report the case of a 30-year-old woman operated for bladder
      endometriosis who presented with recent menstrual macroscopic haematuria with
      primary infertility and deep dyspareunia. Histological examination demonstrated
      bladder endometriosis sparing the urothelium. Comparison with our histological
      series of bladder endometriosis demonstrated polymorphic lesions ranging from
      integrity to complete loss of the bladder mucosa, with no correlation with
      clinical features.

PMID- 16097158
TI  - [Urachal sinus. Report of 3 cases].
AB  - Urachal sinus is a congenital anomaly secondary to insufficiently high
      obliteration of the urachus. It can present clinically at any age with purulent
      umbilical discharge. A combination of ultrasound and fistulography is essential
      to confirm the diagnosis. There is a risk of adenocarcinomatous degeneration.
      Treatment consists of resection of the sinus and its implantation base on the
      bladder. Excision of the umbilicus is not mandatory in children. The authors
      report a retrospective analysis of 3 cases of urachal sinus in 3 girls with a
      mean age of 12 years, presenting a 3-month history of purulent umbilical
      discharge before admission. An umbilical nodule was detected in 2 patients and an
      infraumbilical spindle-shaped mass was observed in the third patient. Ultrasound
      showed an infraumbilical echogenic mass and fistulography, performed in 2
      patients, showed a blind cavity directed inferiorly, confirming.the urachal
      sinus. Treatment consisted of complete resection of the sinus in one patient and
      complete resection of the sinus and its implantation base on the bladder in the
      other 2 patients. An associated teratoma of the right ovary was found in one
      patient. The postoperative course was uneventful. Umbilicoplasty, performed in 2
      patients with resection of the umbilicus, was satisfactory. No recurrence was
      observed with a mean follow-up of 12 months. Histological examination did not
      reveal any signs of malignancy. Purulent umbilical discharge may indicate the
      presence or urachal sinus, which can be confirmed by a combination of ultrasound
      and fistulography. Treatment consists of resection of the sinus and its
      implantation base on the bladder. The objective of this study was to define the
      diagnostic and therapeutic features of urachal sinus.

PMID- 16097159
TI  - [Giant ureteric stones: report of two cases].
AB  - Ureteric stones are generally solitary and less than 2 cm long. Exceptionally,
      ureteric stones can be longer than 5 cm and/or weigh more than 50 grams, and are
      referred to as giant ureteric stones. In the light of two personal cases and a
      review of the literature, the authors review the epidemiological,
      aetiopathogenic, clinical and therapeutic aspects of this disease with particular
      emphasis on the importance of the aetiological work-up. These two cases concerned
      two boys, aged 10 years and 4 and a half years, respectively, with no particular
      medical history, who presented an acute episode of pyelonephritis. The KUB plain
      film, renal ultrasound and IVU demonstrated a huge stone filling the right ureter
      in one case and the left ureter in the other case. The stones were treated
      surgically in both cases. The aetiopathogenesis of these large ureteric stones
      remains unclear. A urinary tract malformation (megaureter, ureterocele,
      stricture, etc.), either alone or associated with a metabolic predisposition
      plays an important role in the pathogenesis of these large stones. The
      aetiological work-up of these large stones is essential. Morpho-constitutional
      stone analysis provides extremely useful and even decisive information in some
      cases for the aetiological diagnosis. Despite the development of extracorporeal
      lithotripsy and endourological techniques, the treatment of giant ureteric stones
      often remains surgical.

PMID- 16097160
TI  - [Malacoplakia in children].
AB  - Malakoplakia is a rare inflammatory disease, related to Enterobacteria infection
      in the context of a disorder of cell-mediated immunity. This disease does not
      have any specific clinical or laboratory signs and the diagnosis is exclusively
      based on histology. Malakoplakia is exceptional in children and usually involves
      the gastrointestinal tract. The authors report a rare case of malakoplakia of the
      urinary bladder in a 4-year-old child, in whom the initial diagnosis was an
      anomaly of the urachus.

PMID- 16097161
TI  - [Pyelogenic cyst in children].
AB  - Pyelogenic cyst is an intraparenchymal renal cavity lined by transitional cell
      epithelium which communicates with a calyx via a neck. It is a rare disease,
      often discovered incidentally. The diagnosis is based on imaging. Asymptomatic
      forms require simple surveillance and surgical management is only indicated in
      forms complicated by urinary tract infections or stones. In the light of a case
      of pyelogenic cyst revealed by upper urinary tract infection in a 12-year-old
      girl, the authors recall the clinical, histological and therapeutic features of
      this rare disease.

PMID- 16097162
TI  - [Hydronephrosis due to retrograde ureteric intussusception].
AB  - Ureteric intussusception is exceptional. The authors report a case of
      hydronephrosis due to retrograde intussusception of the subpelvic ureter in a 3
      month-old boy admitted for respiratory distress syndrome associated with fever of
      39 degrees C. Imaging revealed the presence of marked dilatation of the left
      kidney. Surgical exploration demonstrated hydronephrosis secondary to obstruction
      due to ureteric intussusception. This is the first case of ureteric
      intussusception reported in a child.

PMID- 16097163
TI  - [Medium and long-term evaluation of spongioplasty in hypospadias repair].
AB  - INTRODUCTION: Spongioplasty for the treatment of hypospadias consists of
      tubulization urethroplasty combined with dissection and midline approximation of
      the two divergent hemicorpora spongiosa. The objective of this study was to
      evaluate the medium-term and long-term cosmetic and functional results, and
      satisfaction of patients operated by this technique. MATERIAL AND METHODS: Fifty
      spongiopasties were performed by the same surgeon between 1990 and 1996. Foreskin
      reconstruction was performed in 40 patients. 48 patients were reviewed between
      2002 and 2003. RESULTS: The immediate results revealed fistula in 8% of cases,
      meatal stricture in 4% of cases, and foreskin complications in 14% of cases. The
      long-term results showed persistence of an unsightly operative scar in 8% of
      cases, residual chordee in 6% of cases, meatal retraction in 8% of cases, and
      persistent partial stricture in 4% of cases. 92% of patients declared that they
      were satisfied with the results of surgery. CONCLUSION: The immediate results of
      spongioplasty are similar to those obtained by other techniques and long-term
      follow-up shows maintenance of the cosmetic and functional results.

PMID- 16097164
TI  - [The association of patient position in lithotomy and lower extremity compartment
      syndrome].

PMID- 16097165
TI  - [Renal cell carcinoma and trichloroethylene].
AB  - The authors report the case of a 51-year-old man with a history of
      trichloroethylene (TCE) poisoning. He was treated by radical nephrectomy after
      discovery ofa right renal mass corresponding to renal cell carcinoma. The
      objective of this study is to discuss the role of TCE abuse as a renal
      carcinogen. TCE is an excellent solvent used to degrease metal parts. It can
      enter the body by inhalation, ingestion or cutaneous contact, but the respiratory
      tract is the main route of absorption of TCE. Many epidemiological studies have
      been conducted on workers exposed to TCE, but they have not been able to clearly
      establish a link between exposure by inhalation to TCE and cancer. The
      International Agency for Research on Cancer has accumulated sufficient evidence
      to consider TCE to be carcinogenic to animals and considers that TCE is probably
      carcinogenic to humans. Toxic metabolites derived from TCE induce chronic renal
      tubular lesions and may exert a genotoxic effect on the proximal convoluted
      tubule. The initial genotoxic effect appears to be related to mutations of the
      VHL suppressor gene. The chronic toxic effects and the possible role of TCE in
      the development of cancer have not been specifically studied in the context of
      TCE abuse behaviour. To our knowledge, this is the first case of renal cell
      carcinoma reported in a TCE addict.

PMID- 16097166
TI  - [Urinary bovine tuberculosis in man].
AB  - Human infestation by Mycobacterium bovis has become rare since eradication of
      bovine tuberculosis. However, this aetiology must be envisaged, as the
      sensitivity of the micro-organism is variable and its demonstration requires
      specific techniques.

PMID- 16097167
TI  - [Adrenal myelolipoma].
AB  - Adrenal myelolipoma is a benign, non-secreting tumour, which can be complicated
      by pain or retroperitoneal haemorrhage. The diagnosis is based on CT or
      preferably MRI. Surgery may be necessary in the case of complications. The
      contribution of interventional radiology has not been reported in the literature
      and selective embolization has also not been previously reported.

PMID- 16097168
TI  - [Skin metastasis from invasive bladder tumour].
AB  - Metastatic spread of advanced transitional cell bladder carcinoma rarely involves
      the skin. However, the presence of a skin metastasis indicates at least
      microscopic dissemination of cancer cells to the liver or lung, corresponding to
      a poor prognosis. The authors report a new case of single skin metastasis during
      the course of a poorly differentiated stage pT3a N0 M0 transitional cell bladder
      carcinoma. The patient died 5 months after the appearance of the skin metastasis.

PMID- 16097169
TI  - [Leiomyosarcoma of the renal pelvis].
AB  - Leiomyosarcoma of the renal pelvis is an exceptional tumour, as only 3 cases have
      been reported in the literature. The authors report a new case and discuss the
      differential diagnoses and prognosis of this lesion.

PMID- 16097170
TI  - [How to avoid accumulation of stone fragments in the lower calix during flexible
      ureterorenoscopy].
AB  - Flexible ureterorenoscopy combined with Holmium:YAG laser is an emerging
      technology that already has its place among the urologist's treatment options for
      the management of urinary stones. The main indication for the technique is renal
      stones, particularly lower caliceal stones. After mobilization of the stone in
      the renal pelvis or upper caliceal group, fragmentation is achieved by
      Holmium:YAG laser and the largest fragments are removed. When small fragments
      persist that are difficult to extract, the patient's blood is injected into the
      lower caliceal group to obtain a blood clot This clot then fills the lower
      caliceal group and prevents secondary accumulation of residual stone fragments,
      facilitating elimination of fragments towards the ureter. This article describes
      this technique.

PMID- 16097171
TI  - [The urology in the anatomical plates of Andreas Vesalius (1514-1564)].
AB  - Perspicacious and methodical as much as genius, Vesalius was the greatest
      anatomist of all time. He created the anatomical nomenclature of organs used even
      today. He elaborated more than 300 remarkable anatomical illustrations, a part of
      which is dedicated to the male urogenital tract, providing in this way precious
      information about the knowledge on urology of his time.

PMID- 16097172
TI  - [TBE vaccines are exchangeable--but not completely. Children in high-risk regions
      can also need protection].

PMID- 16097173
TI  - [Pediatric cardiology--a Swedish matter].

PMID- 16097174
TI  - [Catheter interventions in congenital heart defects as alternatives to open
      surgery].

PMID- 16097175
TI  - [Mild mental retardation--time to look over the definition and terminology].

PMID- 16097176
TI  - [Gradually improved long-term survival in diabetes. Long disease duration can
      provide information about protective possibilities].
AB  - Studies on patients with long-term diabetes survival without severe complications
      can give information about protective factors. Therefore, the present study aims
      to describe the long-term survival of patients with diabetes during successive
      periods following the introduction of insulin therapy in 1923. After registration
      in 1973 of the first local diabetic patient in Jonkoping with a fifty-year
      survival, this group has successively increased. Of those who were diagnosed
      during the period 1940 through 1949 there was a fifty-year survival in about one
      third. The successively better survival emphasises the importance of therapeutic
      progress. The study found no difference in diabetes control between those
      surviving 50 years and those with an age-matched group with a survival of 15
      years. The insulin dose tended to decrease after 30 years duration. Peripheral
      vibration sensibility as well as renal function deteriorated by longer duration.
      The serum ratio of HDL-cholesterol to triglycerides increased. The frequency of
      glaucoma, cataract, and a history of myocardial infarction increased. In spite of
      long duration, one third of the sample had escaped serious retinopathy.

PMID- 16097177
TI  - [Acute hepatitis in a woman after intake of slimming pills bought via Internet].

PMID- 16097178
TI  - [Suspected acute coronary syndrome].

PMID- 16097179
TI  - [Asylum seeking children...authorities are waiting and demanding "all the facts".
      All necessary knowledge already exists--accusation of malingering should be
      condemned].

PMID- 16097180
TI  - [The National Board of Forensic Medicine will be responsible for legal
      certification].

PMID- 16097181
TI  - [Drug committees are not necessary--therapeutic recommendations are issued
      anyway].

PMID- 16097182
TI  - [Explanation on indications and cost-efficiency of Inspra].

PMID- 16097183
TI  - [Inspra and the drug benefits board: What is the role of the drug committees?].

PMID- 16097184
TI  - [Easier to choose the best surgeon].

PMID- 16097186
TI  - [TGA: Clinical assessment is sufficient in the investigation!].

PMID- 16097185
TI  - [Don't do the allergy testing at home!].

PMID- 16097187
TI  - [How do you stand while urinating--does it tell anything about prostatic
      hypertrophy?].

PMID- 16097188
TI  - [Authors should know who reviewed their articles].

PMID- 16097189
TI  - The preacher who's raising hell with Merck.

PMID- 16097190
TI  - Drug testing goes offshore.

PMID- 16097191
TI  - Helping employees stay healthy.

PMID- 16097193
TI  - Has the wall come down for ever?

PMID- 16097194
TI  - Sparrows take flight.
AB  - Sparrow Schools offer a lifeline for disadvantaged children in South Africa--many
      of whom have lost parents to HIV/AIDS. The schools are supported by a charitable
      foundation in the U.K. and were the RCN president's chosen charity at this year's
      congress.

PMID- 16097195
TI  - The big question.
AB  - As yet, few centres in the U.K. have the expertise to perform bariatric surgery
      for obese people. But the need for such surgery is growing and one unit is
      providing healthcare staff with training.

PMID- 16097196
TI  - War of the worlds.

PMID- 16097197
TI  - Return-to-practice initiatives in nursing retention.
AB  - Return-to-practice is an important issue for NHS employers and employees.
      However, little has been written on this area. This article reviews current
      literature from the perspective of nurses, employers and managers, and critiques
      a number of empirical studies. Findings from a recent telephone interview survey
      on the recruitment and retention of nurses in acute NHS trusts in England which
      was conducted as part of a larger study--the Nurses' Early Leaving Study (NEXT)
      commissioned by the European Union--are reported. This study may help to explain
      why return-to-practice programmes are not having the impact the government
      intended.

PMID- 16097198
TI  - Malaria: awareness and compliance with preventive measures.
AB  - Many articles have been written on malaria, but few have addressed travellers'
      awareness and compliance with preventive measures. The U.K. has an increasing
      number of travellers visiting high-risk destinations and undertaking high-risk
      activities, who either do not seek pre-travel advice or do not act on it.
      Community involvement, developing cultural competence and improved communication
      may help to raise awareness and encourage travellers to seek advice and change
      their behaviour.

PMID- 16097199
TI  - Peripheral intravenous therapy: key risks and implications for practice.
AB  - Personnel, environment and procedures related to peripheral intravenous (IV)
      therapy are explained. Parenteral routes are suggested and, where peripheral IV
      therapy is required, recommendations are made to minimize risk of anaphylaxis and
      infection.

PMID- 16097200
TI  - Nightlife and health.

PMID- 16097201
TI  - A liberating experience.

PMID- 16097202
TI  - Home schooling.

PMID- 16097203
TI  - [Meeting with the refusal of care, democracy is required].

PMID- 16097204
TI  - [Drug interactions in an elderly population. Prospective assessment of their
      frequency and seriousness among 56 patients].
AB  - OBJECTIVE: To assess the nature and the number of potential adverse drug
      interactions by analysis of outpatient prescriptions for elderly patients, of
      medications taken during the week before hospitalization in a general surgery
      department. METHOD: The study of 56 patients older than 65 years was conducted
      from November 2002 through February 2003. The outpatient prescriptions
      corresponding to medications taken during the 7 days before admission were
      analyzed by a pharmacy resident, who used data-processing tools and databases.
      RESULTS: Most patients (83%) knew the reason for their prescription. Thirteen
      (28%) reported using over-the-counter medication. Only 89% of the patients
      reported complete compliance with the prescription. The average age of the
      patients was 72.1 +/- 6.3 years and the median was 71 years [65-91]; 43% were
      women and 57% men. The 257 lines of prescriptions analyzed averaged 5.7 +/- 2.6
      drugs (range: 2-10) per prescription. The average number of possible interactions
      was 3.1 +/- 2.8 per prescription for a total of 89 listed potential interactions.
      The levels observed were 3 warnings (3%), 37 precautions (42%) and 49 possible
      adverse interactions (55%). No contraindication was noted. The drugs mentioned
      most often were benzodiazepines, diuretics, conversion enzyme inhibitors,
      angiotensin II inhibitors, and beta-blockers. The potential risks most often
      found were hypotension, depression of the central nervous system, hypoglycemia
      and acute renal failure. The drug interactions were mainly due to the
      accumulation of the effects of separate drug classes. Deterioration in renal
      function was often noted as plasma concentration of the second drug increased.
      DISCUSSION: This exploratory study shows the reality of the iatrogenic risk for
      elderly patients. This analysis of outpatient prescriptions is consistent with
      findings in the literature. Analysis of interactions is conducted on a pairwise
      basis. It is thus difficult to envisage the consequences of the association of 5
      or more drugs in patients with complex illnesses and diminished physiological and
      metabolic capacity. Patient files kept by the pharmacist could provide
      information about individual combinations ofthe prescription and over-the-counter
      drugs.

PMID- 16097205
TI  - [Trends in the pharmaceutical profile of intentional drug overdoses seen in the
      emergency room].
AB  - OBJECTIVES: The aim of the study was to investigate trends in substances used for
      acute self-administered drug overdoses (SADO). METHOD: Review of all SADO
      emergency room visits over two 1-year periods during 1992-1993 (P1) and 2001-2002
      (P2). RESULTS: We compared 804 SADO episodes in P1 with 830 in P2. Patient
      characteristics did not differ significantly during the two periods (predominance
      of women: 66 vs 69%; mean age: 33 +/- 12 vs 37 +/- 13.5 years). Psychotropic
      drugs predominated in both periods (78 and 77%), but the prevalence of
      benzodiazepines declined (67 to 55%; p < 0.01) and that of antidepressants
      increased (9.5 to 15%; p < 0.01). Bromazepam was the ben-zodiazepine used most
      often during both periods (P1: 30% and P2: 35%), but the use of aprazolam
      increased (from 6 to 17%; p < 0.01). Among the antidepressants, the use of
      tricyclics decreased (from 43 to 14%; p < 0.01) and that of selective serotonin
      reuptake inhibitors increased (31 to 71%; p < 0.01). The proportion of
      benzodiazepine-related drugs increased over time (8.1 to 14%: p < 0.01). The
      other therapeutic classes remained quite similar to each other between P1 and P2,
      except for anti-inflammatories (P1: 1.3%, P2: 2.7%; p = 0.01). Among the
      analgesics, paracetamol alone or combined with other agents predominated (68 and
      64% respectively), but use of opiate analgesics was fre-quent during the later
      period (2.7 vs 22%; p < 0.01). CONCLUSION: The trend of the different
      pharmacological families used in SADO seen in the emergency room has not
      fundamentally changed over the past decade. However, qualitative changes within
      the drug classes require emergency physicians to update their knowledge of
      toxicology.

PMID- 16097206
TI  - [Treatment of GP's telephone requests for admission. Assessment of departments
      for 4 medical specialties].
AB  - OBJECTIVES: To assess the capacity of 4 types of medical departments in the Paris
      hospital network (AP-HP) to plan hospitalization following a telephoned request
      from a GP (who do not have hospital admitting privileges). METHOD: Four simulated
      cases were designed to present a specific problem, requiring prompt but not
      urgent admission into a department of internal medicine, rheumatology,
      gastroenterology and neurology. The experiment took place from January 17 through
      12 February 2002, during standard office hours: an investigator posing as a locum
      tenens covering for a general practitioner called the hospital switchboard,
      requested the department, asked to speak to someone able to arrange the
      admission, and provided details of the simulated case. When a single hospital had
      several departments of the same specialty, we made only one telephone call. The
      details recorded in each case were principally the time elapsed for each stage
      and the final result. RESULTS: We contacted 55 medical departments: 19 of the 20
      internal medicine departments in the network, all 9 rheumatology, all 19
      gastroenterology, and 8 of 13 neurology departments. The mean time spent on the
      phone was 5.04 min (range 1.40-10.14, SD 2.20). Justification for the referral
      was never questioned. Twenty-two (40%) referrals succeeded: 10/19 (53%) in
      internal medicine, 4/9 (44%) in rheumatology, 6/19 (32%) in gastroenterology, and
      2/8 (25%) in neurology. Admission could not be arranged in 33 (60%) cases
      because: no one able to arrange the admission was available for 17 cases (31%)
      (the person was in a meeting 9 times and could not be found 8); no bed was
      available in 13 (24%). Alternatives solutions were proposed in 10 of these 13
      cases: call the emergency unit (6/13), or call another hospital (3/13).
      CONCLUSION: Only hospital reorganization and regular assessments can improve the
      procedure for handling GP referrals for admission.

PMID- 16097207
TI  - [Physicians' opinions about the implementation of clinical practice guidelines
      for gastrointestinal oncology].
AB  - OBJECTIVE: To assess the physicians' use of clinical practice guidelines (CPG)
      for gastrointestinal oncology. METHOD: Quantitative study with semistructured
      individual interviews of 17 physicians treating patients with gastrointestinal
      cancer in the Rhone district of France. RESULTS: The interviews identified 7
      major themes: issues associated with development of the CPG; their usefulness in
      the physician-patient relationship; their ease of application; relevance of the
      specific topic; the procedures used for their development; the methods for
      disseminating them; and monitoring of their impact. CONCLUSION: The physicians
      were relatively favorable to the CPG but stressed the need for greater
      transparency about related issues and effects, economic and legal, in particular,
      for dissemination through multiple and novel communication tools, and for
      assessment of their impact.

PMID- 16097208
TI  - [Idiopathic lumbosacral plexopathy].
AB  - INTRODUCTION: Lumbosacral plexopathy is the equivalent in the lower limbs of
      neuralgic amyotrophy (also known as Parsonage-Turner syndrome) in the upper
      limbs. It is well-known in patients with diabetes mellitus, when it is known as
      Bruns-Garland syndrome. CASE: We report the case of a 47-year-old woman who
      developed a unilateral neuropathy of the leg, neither radicular nor truncal in
      origin. The slow continuous improvement was not affected by any of the treatments
      administered. DISCUSSION: Lumbosacral plexopathy is characterized by intense pain
      in one or both legs, associated with motor and sensory deficits. Recovery is
      usually slow (6 to 36 months) and often incomplete. The electrodiagnostic
      examination shows important acute motor and sensory axonal loss, characterized by
      denervation and low-amplitude sensory action potential. Treatment generally
      combines analgesics with narcotic agents, neuropathic pain medication, short-term
      corticosteroids, and rehabilitation. In the most severe cases, long-term
      corticosteroids and other immunosuppressive agents may be required. This
      diagnosis cannot be reached until all other radicular, plexal and truncal origins
      have been ruled out.

PMID- 16097209
TI  - [Calcification following intradiscal injection, a continuing problem?].
AB  - INTRODUCTION: Intradiscal injection of triamcinolone hexacetonide, used to treat
      sciatica caused by herniated discs was discontinued after discovery that it was
      followed in some cases by epidural calcification. OBSERVATION: Ten years after an
      intradiscal injection at L4-L5, a 40 year-old man developed voluminous
      perivertebral, bilateral foraminal and intraductal calcifications that compressed
      the dural sheath. After preliminary excision, these calcifications recurred and
      required further excision, followed by posterior lateral grafting and
      osteosynthesis. DISCUSSION: Calcifications following intradiscal injections are
      symptomatic in 14 to 68% of cases. They require radical surgical treatment to
      avoid recurrence.

PMID- 16097210
TI  - [Familial small-vessel vasculitis of the kidney].
AB  - INTRODUCTION: Familial forms of small-vessel vasculitis has been reported in 14
      families (including this one). CASES: A father and son were both diagnosed with
      renal vasculitis (pauci-immune crescentic glomerulonephritis). Both had
      antimyeloperoxidase autoantibodies, and there was no evidence of a common
      environmental factor. DISCUSSION: These cases suggest the role of constitutional
      factors in the pathogenesis of antineutrophil cytoplasmic antibody-associated
      vasculitis.

PMID- 16097211
TI  - [Mental confusion in the elderly].
AB  - The prevalence of delirium in hospitalized patients aged 80 years or older ranges
      from 35 to 50%. Its onset is acute, recovery is erratic, and the principal
      differential diagnosis is dementia. Hypoactive confusion is a clinical form that
      should not be ignored. Prognosis is severe with impairments in activities of
      daily living and high mortality. Risk factors are age (older than 80 years),
      dementia, sensory impairments, dehydration, sleep deprivation and immobility.
      Initial treatment must focus on identifying the cause of the delirium. Primary
      nonpharmacological prevention in subjects at risk is possible and effective.

PMID- 16097212
TI  - [Acute transverse myelopathy: inflammatory or ischemic?].
AB  - The rapid development of paraparesis or tetraparesis combined with a bilateral
      sensory deficit that has a clearly defined rostral border and bladder dysfunction
      are the principal features of acute transverse myelopathy. Acute partial
      transverse myelopathy is far much more frequent: its symptoms are asymmetric,
      sometimes unilateral, and sensory deficit may predominate. An urgent MRI is
      required to exclude acute spinal cord compression. Diagnosis of ischemic acute
      transverse myelopathy includes the following elements: sudden onset, neurologic
      symptoms compatible with infarction in the anterior spinal artery area (by far
      the most frequent location for spinal cord infarction), and presence of a
      specific cause of spinal cord ischemia. In all other cases where it is difficult
      to distinguish spinal cord infarction from myelitis, analysis of the
      cerebrospinal fluid is essential. Most cases of inflammatory acute transverse
      myelopathy can be linked to a defined cause. Multiple sclerosis is a major cause
      of partial acute transverse myelopathy. MRI lesions are usually small, located in
      the lateral or posterior part of the spinal cord. Diagnostic elements include
      multiple lesions of multifocal demyelination on the cerebral MRI, oligoclonal
      bands in the cerebrospinal fluid, and the absence of clinical or laboratory
      abnormalities that suggest systemic disease. Neuromyelitis optica, also known as
      Devic's disease, has often been considered a variant form of multiple sclerosis.
      Recent immunologic studies confirm the hypothesis that it is a distinct entity.
      Infectious transverse acute myelitis is often of viral origin. It may result from
      direct viral stress but more frequently follows immunologically-mediated indirect
      stress. This acute parainfectious myelitis, like postvaccinal myelitis, may be
      considered as a spinal single-focus form of acute disseminated encephalomyelitis
      (ADEM). It is important to distinguish the latter from an initial episode of
      multiple sclerosis, because their prognosis and treatment differ.

PMID- 16097213
TI  - [Age, an independent risk factor for thrombosis. Epidemiologic data].
AB  - The incidence of thrombosis--arterial and venous--increases with age. This is the
      case for atheromatous diseases, atrial fibrillation and even venous
      thromboembolic disease. Ischemic heart disease is the most common cause of death
      in the elderly. Atrial fibrillation, an independent risk factor for cerebral
      vascular accidents, affects around 10% of persons older than 80 years. The
      incidence of venous thromboembolic disease increases with age, reaching 12.5 per
      1000 people older than 75 years, compared with 5 per 1000 aged 60-75 and 2.5 per
      1000 aged 40-59. Elderly persons often have two or more cardiovascular or venous
      thromboembolic risk factors and thus a still higher risk of thrombotic events.
      Their risk of thrombosis justifies the systematic search for acquired risk
      factors to assess the level of risk and take appropriate prevention measures.

PMID- 16097214
TI  - [What explains the increased rate of thromboses among the elderly?
      Pathophysiological data].
AB  - The incidence of both arterial and venous thrombosis increases with age. The
      explanation is probably multifactorial, since elderly patients often have several
      risk factors. Aging per se appears to be an independent risk factor for
      thrombosis: age-related modifications of the vascular apparatus and blood
      components contribute to the development of a procoagulant state. Arterial and
      venous thromboses involve varying degrees of coagulation and platelet activation.

PMID- 16097215
TI  - [Hypersignal in T1-weighted images of the basal ganglia in hepatic
      encephalopathy].

PMID- 16097216
TI  - Upper lip changes correlated to maxillary incisor retraction--a metallic implant
      study.
AB  - The soft tissue changes after the extraction of maxillary first premolars and
      subsequent anterior tooth retraction were evaluated for 16 Class II, division 1
      patients. Pre- and posttreatment lateral head cephalograms were evaluated using
      superimpositions on Bjork-type metallic implants in the maxilla. The patient
      sample was divided into group I patients, those who did exhibit lip seal at rest
      in the pretreatment cephalogram and group II patients, those who did not exhibit
      lip seal at rest in the pretreatment cephalogram. Upper incisor retraction was
      followed by a similar ratio of upper lip retraction in both the lip seal and
      nonsealed groups (1:0.75 and 1:0.70 mean ratios, respectively). However, those
      without lip seal did demonstrate more retraction at stomion (USt). The final
      upper lip position (Ls) was reasonably correlated with retraction of the cervical
      maxillary incisor point (cU1) with determination coefficients of 63.6% in the lip
      sealed and 68.5% in the lip incompetent groups. Although labial and nasolabial
      angles tended to open after incisor retraction, there was little predictability
      for this response.

PMID- 16097217
TI  - Association between Bjork's structural signs of mandibular growth rotation and
      skeletofacial morphology.
AB  - The aim of this study was to apply Bjork's structural signs of mandibular growth
      rotation to answer the questions: (1) Is a hyperdivergent or hypodivergent
      skeletofacial growth pattern characterized by a specific mandibular morphology?
      (2) Are severe skeletofacial hyperor hypodivergencies recognized more easily than
      mild ones? (3) Are skeletofacial hyper- or hypodivergencies recognized more
      easily in older than in younger subjects? Mandibular cuttings from lateral head
      films of 135 Class I or Class II subjects were surveyed twice by nine observers.
      Of the 135 subjects, 95 subjects exhibited a large (ML/NSL > 38 degrees) and 40 a
      small (ML/NSL < 26 degrees) mandibular plane angle. Using the structural signs of
      mandibular growth rotation, the observers had to categorize the subjects as
      having either a high-angle or low-angle skeletofacial morphology. In 14% (13 of
      95) of the subjects with a large ML/NSL angle, the skeletofacial hyperdivergency
      was recognized in all registrations, but in 19% (18 of 95), the hyperdivergency
      was identified in less than half of the registrations. In 63% (25 of 40) of the
      subjects with a small ML/NSL angle, the skeletofacial hypodivergency was
      recognized in all registrations, whereas in only 2.5% (one of 40), the
      hypodivergency was identified in less than half of the registrations. There was
      no association between the degree of hypo- or hyperdivergency or the age of the
      subjects and the number of correct registrations. Using the structural method of
      Bjork, it was difficult to categorize the subjects as having either a hyperor
      hypodivergent skeletofacial morphology. However, hypodivergency was recognized
      more easily than hyperdivergency.

PMID- 16097218
TI  - Gender differences in Class III malocclusion.
AB  - This study evaluated gender differences in the cephalometric records of a large
      scale cross-sectional sample of Caucasian subjects with Class III malocclusion at
      different developmental ages. The purpose also was to provide average age-related
      and sex-related data for craniofacial measures in untreated Class III subjects
      that are used as reference in the diagnostic appraisal of the patient with Class
      III disharmony. The sample examined consisted of 1094 pretreatment lateral
      cephalometric records (557 female subjects and 537 male subjects) of Caucasian
      Class III individuals. The age range for female subjects was between three years
      six months and 57 years seven months. The male subject group ranged from three
      years three months to 48 years five months. Twelve age groups were identified.
      Skeletal maturity at different age periods also was determined using the stage of
      cervical vertebral maturation. Gender differences for all cephalometric variables
      were analyzed using parametric statistics. The findings of the study indicated
      that Class III malocclusion is associated with a significant degree of sexual
      dimorphism in craniofacial parameters, especially from the age of 13 onward. Male
      subjects with Class III malocclusion present with significantly larger linear
      dimensions of the maxilla, mandible, and anterior facial heights when compared
      with female subjects during the circumpubertal and postpubertal periods.

PMID- 16097219
TI  - Acceptability and perceived effectiveness of web-based self-instruction in
      clinical orthodontics.
AB  - For a predoctoral course in advanced clinical orthodontics, we evaluated the
      acceptability to students (how well did you like it?) and the perceived
      effectiveness (how well did it help you learn?) of Web-based self-instruction
      plus small-group seminars. On a 10-point Likert scale, median scores for
      acceptability and effectiveness of the self-instructional modules and seminars
      were nine. More than half the students rated the modules as excellent, and two
      thirds rated the seminars as excellent. No students rated either the modules or
      the seminars as poor. With the use of structured seminar outlines, there were no
      significant differences in seminar scores among the seminar leaders. Compared
      with their predecessors who had a traditional lecture course, students who had
      the new self-instructional course were less likely to report either the positive
      or negative extremes in confidence about their ability to recognize treatment
      alternatives for orthodontic problems. The results indicate that Web-based self
      instruction plus small-group seminars coordinated by a course leader is at least
      as effective as traditional lectures. This approach offers a possible way to
      share faculty among orthodontic departments for both pre- and postdoctoral
      education, as a way to help overcome faculty shortages.

PMID- 16097220
TI  - Patient compliance: a determinant of patient satisfaction?
AB  - Recent studies have shown that there is a distinct relationship between patient
      satisfaction and patient compliance in orthodontic treatment. The aim of this
      study was to investigate whether patient compliance, as noticed and recorded by
      the orthodontist during treatment, can be used as a determinant of patient's
      satisfaction in the long run. Documentation of 100 patients who completed active
      orthodontic treatment in the year 2000 at the Academic Centre of Dentistry
      Amsterdam was analyzed, and compliance scores for patients were computed. Three
      years after completion of active orthodontic treatment, a questionnaire about
      satisfaction was sent to all subjects. Items were divided over six subscales on
      the basis of item content. Compliance and satisfaction scores of both sexes were
      compared, and correlations between compliance and satisfaction were explored.
      Regression analyses were done to examine the predictive value of sex and
      compliance on patient satisfaction. No significant correlations between
      compliance and satisfaction scores were found. Sex, but not compliance, predicted
      the patient's satisfaction with the doctor-patient relationship and the
      situational aspects of the treatment. Compliance, as noticed and recorded by the
      orthodontist during treatment, is not a decisive determinant of patient
      satisfaction in the long run. Sex, however, is a predictor of patient
      satisfaction with regard to the doctor-patient relationship and the situational
      aspects of the orthodontic treatment.

PMID- 16097221
TI  - Efficiency of noncompliance simultaneous first and second upper molar
      distalization: a three-dimensional tooth movement analysis.
AB  - Objective of this prospective study was the three-dimensional (3D) analysis of
      tooth movements after the noncompliance simultaneous distalization of the first
      and second maxillary molars. Ten patients (five girls and five boys; mean age:
      13.2 years) with bilateral Class II molar relationships were treated with a
      noncompliance, fixed intraoral appliance. Upper second molars had already erupted
      in all cases. Dental casts and lateral cephalometric radiographs were taken
      immediately before placement and after removal of the appliance. The casts were
      3D digitized and superimposed on a predefined area in the palate. The resulting
      holograms, as well as the cephalometric radiographs, were digitized and analyzed
      by means of customized cephalometric software. The whole procedure was repeated
      after a two- to four-week interval to estimate the error of both methods. The
      cast assessment of 3D sagittal and vertical tooth movements was more reliable
      than the cephalometric record. The average maxillary first molar distal movement
      was 2.8 mm. Anchorage loss was expressed by a 1.9-mm proclination of the central
      incisors. A substantial variation among patients and among the right and left
      side in the same patient was observed. Noncompliance simultaneous distalization
      of the first and second maxillary molars can be an efficient treatment option for
      the correction of Class II molar relationship. However, anchorage loss and
      individual variation have to be seriously considered. Bilaterally symmetrical
      effectiveness should not be relied upon.

PMID- 16097222
TI  - Short-term treatment effects produced by the Herbst appliance in the mixed
      dentition.
AB  - This prospective clinical investigation evaluates the dentoalveolar and skeletal
      cephalometric changes produced by the Herbst appliance during treatment of mixed
      dentition patients with Class II division 1 malocclusion. Thirty individuals (15
      male and 15 female individuals; initial mean age nine years 10 months) were
      treated with the Herbst appliance for a period of 12 months. For comparison, the
      records of 30 untreated Class II children (15 boys, 15 girls; initial mean age
      nine years eight months) were followed without treatment for a period of 12
      months. The results indicated that the treatment effects produced in the mixed
      dentition patients were primarily dentoalveolar in nature. The mandibular
      incisors were tipped labially, and the maxillary incisors were retruded; a
      significant increase in mandibular posterior dentoalveolar height occurred, and
      there was a restriction in the vertical development of the maxillary molars.
      There was no difference in the forward growth of the maxilla between the two
      groups. In comparison with the controls, however, the Herbst treatment produced a
      modest but statistically significant increase in total mandibular length. This
      increase in total mandibular length, however, was less than that observed in
      adolescent Herbst patients in other studies.

PMID- 16097223
TI  - Rapid maxillary expansion--tooth tissue-borne versus tooth-borne expanders: a
      computed tomography evaluation of dentoskeletal effects.
AB  - This study evaluated rapid maxillary expansion (RME) dentoskeletal effects by
      means of computed tomography (CT), comparing tooth tissue-borne and tooth-borne
      expanders. The sample comprised eight girls aged 11 to 14 years presenting Class
      I or II malocclusions with posterior unilateral or bilateral crossbite that were
      randomly divided into two treatment groups, palatal acrylic (Haas-type) and
      hygienic (Hyrax) expanders. All appliances were activated up to the full seven mm
      capacity of the expansion screw. The patients were subjected to a spiral CT scan
      before expansion and after a three-month retention period when the expander was
      removed. One-millimeter-thick axial sections were scanned parallel to the palatal
      plane, comprising the dentoalveolar area and the base of the maxilla up to the
      inferior third of the nasal cavity. Multiplanar reconstruction was used to
      measure maxillary transverse dimensions and posterior teeth inclination by means
      of a computerized method. The results showed that RME produced a significant
      increase in all measured transverse linear dimensions, decreasing in magnitude
      from dental arch to basal bone. The transverse increase at the level of the nasal
      floor corresponded to one-third of the amount of screw activation. Tooth-borne
      (Hyrax) and tooth tissue-borne (Haas-type) expanders tended to produce similar
      orthopedic effects. In both methods, RME led to buccal movement of the maxillary
      posterior teeth, by tipping and bodily translation. The second premolars
      displayed more buccal tipping than the appliance-supporting teeth. The tooth
      tissue-borne expander produced a greater change in the axial inclination of
      appliance-supporting teeth, especially first premolars, compared with the tooth
      borne expander.

PMID- 16097224
TI  - Molar distalization with a modified pendulum appliance--in vitro analysis of the
      force systems and in vivo study in children and adolescents.
AB  - The standard pendulum appliance was modified by integrating a distal screw into
      its base and by special preactivation of the pendulum springs. The suitability of
      this Pendulum K for the translatory distalization of maxillary molars was
      investigated in an in vitro analysis and in an in vivo study in children and
      adolescents. The in vitro measurement of the resulting force systems revealed
      that all forces and moments remained virtually constant over a three-mm simulated
      distalization increment. The transverse force, Fx, increased from two to 11 cN
      and the weakly intrusively acting force, Fy, from six to eight cN, but these
      increases were not statistically significant. The distalization force, Fz,
      initially 201 cN, was still 199 cN after a three-mm distalization increment. The
      mesially acting moment, My, rose from 1654 to 1834 cN mm, whereas the palatally
      acting moment, Mz, declined slightly from 229 to 164 cN mm. The slight,
      consistent distoinclinatory moment, Mx, initially 306 cN mm, was 310 cN mm after
      three mm. In parallel, the in vivo study with its collective of 66 patients
      confirmed that the Pendulum K allows a virtually translatory molar distalization
      with slight tippings of 4.75 degrees to the palatal plane and 4.25 degrees to the
      anterior basal plane. Palatal movements of the first molars were avoided. The
      proportion of molar distalization in the total movement was 73.53%.

PMID- 16097225
TI  - Magnetic resonance imaging of the condylar growth pattern and disk position after
      chin cup therapy: a preliminary study.
AB  - This study was conducted on lateral cephalograms and magnetic resonance images
      (MRIs) obtained from 20 subjects with Class III malocclusion. Only clinically
      temporomandibular joint (TMJ) symptom-free subjects were included in this study.
      In the treatment group, a chin cup with 600 g of force was applied in 13 patients
      (10 girls and three boys) with a mean age of nine years. The chin cup was applied
      in a direction from the chin toward the TMJ. The control group consisted of seven
      patients (six girls and one boy) with a mean age of eight year nine months.
      Orthodontic treatment was not applied in the control group. Records were taken at
      the beginning and end of chin cup therapy from all the subjects. Measurements
      were made on lateral cephalograms and unilateral-left sagittal-oblique TMJ MRIs.
      Variables obtained at the beginning and end of the study were compared by
      Student's t-tests and paired t-tests. Relationships between craniofacial and TMJ
      variables were analyzed by correlation analysis. The mandibular corpus length was
      increased and condylar head angle was decreased by chin cup therapy. A positive
      correlation existed between activation of sagittal maxillary and mandibular
      growth and bending of the condylar head. This study showed that the condylar
      growth pattern was altered by chin cup. It may be implied that the source of
      improvement is adaptation of the craniofacial structures to the changes of the
      condylar growth pattern produced by the chin cup.

PMID- 16097226
TI  - Chin cup treatment outcomes in skeletal Class III dolicho- versus
      nondolichofacial patients.
AB  - This study examines cephalometric differences and sex differences in the long
      term outcome of chin cup treatments of Class III subjects with two facial
      patterns. Seventeen nondolichofacial and 16 dolichofacial Class III male patients
      and 16 nondolichofacial and 16 dolichofacial female patients were treated by
      either bicuspid extraction or nonextraction. Rapid palatal expansion without
      maxillary protraction was performed on 11 male cases and 15 female cases. The
      borderline between the two groups was drawn either at 39 degrees mandibular plane
      angle or 132 degrees (male subjects) or 130 degrees (female subjects) gonial
      angle. Dolichofacial subjects were treated with either an occipital or a high
      pull chin cup force during the first two years, followed by high-pull force
      during night-time wear for the subsequent three years. All treated cases showed
      excellent results in the retention records with acceptable posterior occlusion as
      well as excellent skeletal and soft-tissue profiles. In addition, patient
      compliance was excellent. The treatment outcomes of the two groups showed
      significant improvement of the skeletal Class III malocclusion. This study
      indicated that the treatment period and wear time of the chin cup appliance in
      nondolichofacial (mostly mesiofacial pattern) patients could be shorter than
      those of dolichofacial patients. Although all subjects showed significant
      improvement in the Class III malocclusion, the treatment outcome in the two
      groups maintained the original characteristic skeletal morphology at retention.

PMID- 16097227
TI  - Dentofacial effects of asymmetric headgear and cervical headgear with removable
      plate on unilateral molar distalization.
AB  - Cervical headgear (CHG) is used widely in the treatment of Class II anomalies.
      Asymmetric headgear (AHG) is an alternative treatment for the correction of
      unilateral Class II dental relationships. The purpose of this investigation was
      to compare the effects of AHG with those of a CHG combined with a removable plate
      in unilateral first molar distalization. The study consisted of 20 patients with
      unilateral Class II molar relationship (12 girls and eight boys). One group of 10
      patients was treated with an AHG, and a second group of 10 patients was treated
      with a CHG and a removable plate. Lateral cephalograms and basilar radiographs
      were taken before and after molar distalization. It was found that distalization
      and distal tipping of molar on the passive side was less in the CHG and removable
      plate (CHG-RP) group. Distalization and distal tipping of the second premolar on
      the distalization side was also reduced in this group. Incisors were retruded in
      both groups but were retruded more in the CHG-RP group.

PMID- 16097228
TI  - Anchorage effects of a palatal osseointegrated implant with different fixation: a
      finite element study.
AB  - The purpose of this study was to compare the anchorage effect of the
      osseointegrated implant with different fixation types using finite element
      analysis. Three fixation types were investigated. fixation type 1: implant neck
      in the oral-palatal cortical bone and implant tip in the cancellous bone;
      fixation type 2: implant neck in the oral-palatal cortical bone and implant tip
      in the nasal-palatal cortical bone; fixation type 3: implant neck in the oral
      palatal cortical bone and implant tip projecting into the nasal cavity. Three
      finite element models were constructed. Each consisted of two maxillary second
      premolars, their associated periodontal ligament (PDL), alveolar bones, palatal
      bone, palatal implant, and a transpalatal arch. Another model without an implant
      was used to compare with the previous models. The horizontal force (mesial five
      N, palatal one N) was loaded at the buccal bracket of each second premolar. The
      stress was calculated in the PDL and implant surrounding bone. The result showed
      that the palatal implant could significantly reduce von Mises stress (maximum von
      Mises stress was reduced 30%) and evenly distribute stress in the PDL. The stress
      magnitude and distribution in the PDL was almost the same in the three implant
      models. These results suggest that different implant fixation types have almost
      the same anchorage effects.

PMID- 16097229
TI  - Group distal movement of teeth using microscrew implant anchorage.
AB  - The purpose of this study was to quantify the treatment effects of distalization
      of the maxillary and mandibular molars using microscrew implants. The success
      rate and clinical considerations in the use of the microscrew implants were also
      evaluated. Thirteen patients who had undergone distalization of the posterior
      teeth using forces applied against microscrew implants were selected. Among them,
      11 patients had mandibular microscrew implants and four patients had maxillary
      implants, including two patients who had both maxillary and mandibular ones at
      the same time. The maxillary first premolar and first molars showed significant
      distal movement, with no significant distal movement of the anterior teeth. The
      mandibular first premolar and first and second molars showed significant distal
      movement, but no significant movement of the mandibular incisor was observed. The
      microscrew implant success rate was 90% over a mean application period of 12.3 +/
      5.7 months. The results might support the use of the microscrew implants as an
      anchorage for group distal movement of the teeth.

PMID- 16097230
TI  - Ectopic eruption of the maxillary first permanent molar: characteristics and
      occurrence in growing children.
AB  - The purpose of this study was to determine the characteristics and occurrence of
      the ectopic eruption of the maxillary first permanent molar in a sample of
      growing Spanish children. A descriptive, observational, retrospective study was
      done using the radiographs of 509 consecutive patients, who were in the first
      phase of mixed dentition. A method was designed to evaluate the amount of
      pathologic resorption of the second maxillary primary molar and the impaction of
      the first permanent molar measured in millimeters. Statistical analysis of the
      studied variables was done using chi-square, analysis of variance, and Pearson
      correlation coefficient. The frequency of occurrence was 4.3% with no differences
      in both sexes. Of these, 36.4% were unilateral and 63.6% bilateral with a
      right:left relation of 3:1. Of the 36 ectopic molars, 69.4% self-corrected
      spontaneously. In such cases, the pathological resorption of the root of the
      second maxillary primary molar and its adverse clinical implications were
      persistent. The relation between self-correction and impaction was 2.27:1. The
      average impaction on the right side was 2.91 mm and 1.6 mm on the left side.
      Correlation between the magnitude of resorption and grade of impaction was not
      observed. Although resorption was found on grades I and II, spontaneous self
      correction could occur without arch length loss. However, on grade III or more,
      therapeutic intervention has to be done. The benefit of early diagnosis and
      treatment of the maxillary first permanent molar is the prevention of the
      premature loss of second maxillary deciduous molar and the resulting
      malocclusion.

PMID- 16097231
TI  - Influence of functional appliances on masticatory muscle activity.
AB  - The purpose of the present study was to investigate the influence of an activator
      appliance and a spring active appliance on masticatory muscle activity by means
      of electromyography (EMG). Twelve adult males with good general health were
      recruited as subjects. Three functional appliances were used in each subject for
      long-period EMG recording during daytime and sleep and short-time EMG recording
      during voluntary biting. Following findings were obtained. (1) The activity of
      all muscles was greater during biting than during daytime and sleep, (2) the
      muscle activities tended to increase in the digastric muscle and to decrease in
      the temporal muscle with activators under all conditions, and (3) the temporalis
      masseter ratios became lower with the biting use of appliances. Therefore, this
      study suggests that functional appliances should be used during sleep and during
      the day in combination with voluntary biting to achieve adaptation and
      development of the masticatory muscles.

PMID- 16097232
TI  - Masticatory demands induce region-specific changes in mandibular bone density in
      growing rats.
AB  - This study investigates the structural adaptation of the mandibular bone when
      subjected to different masticatory functional and mechanical demands during
      growth. The effect of two experimental factors, the insertion of a bite block and
      the alteration of food consistency, on the bone mineral density (BMD) of the
      mandible was investigated in growing rats. Fifty-two male albino rats were
      divided into two equal groups, fed with either the standard hard diet or soft
      diet, at the age of four weeks. After two weeks, half the animals in both groups
      had their upper molars fitted with an upper posterior bite block. The remaining
      animals served as a control. Region-specific BMD of the mandible was subsequently
      measured using dual-energy X-ray absorptiometry (DXA). Soft diet and the
      consequent reduction of the forces applied to the mandible during mastication
      resulted in the reduction of BMD in all regions under study. The insertion of the
      bite-opening appliance (bite block) and the resulting stretching of the soft
      tissues led to the application of a continuous light force on the lower molars,
      which was associated with a significant increase of the BMD in the part of the
      alveolar process just below the root apices. These results raise the question of
      whether orthodontic treatment with similar appliances may have some, previously
      unsuspected, short- or long-term effects on the mandibular bone during growth and
      whether their effects depend on the individual soft-tissue characteristics.

PMID- 16097233
TI  - Levels of interleukin-8 during tooth movement.
AB  - A host-derived neutrophil-activating cytokine interleukin-8 (IL-8) is secreted
      mainly by monocytes and is considered to be important in regulating alveolar bone
      resorption during tooth movement. The aim of this study was to evaluate the
      levels of IL-8 during mechanical forces on periodontal tissues at different
      stages of orthodontic therapy. Ten canine teeth of patients having different
      Angle classifications were selected for the study. After the premolars were
      extracted, the maxillary/mandibular canines were tipped distally. Gingival
      crevicular fluid was sampled from mesial and distal gingival crevices of each
      canine separately at baseline and one hour, 24 hours, six days, 10 days, and 30
      days after the application of the force. An enzyme-linked immunosorbent assay for
      quantitative detection of IL-8 was used. Although there was an increase in the
      concentration of IL-8 at tension (mesial) sites after one hour, 24 hours, six
      days, and 10 days, a decrease was observed at 30 days. Pressure (distal) sites
      did not demonstrate such an increase at any period except at 10 days. However,
      the concentration of IL-8 at both sites showed a similar decrease and approached
      each other at day 30. We concluded that local host response toward the
      orthodontic forces might lead an increase in IL-8 and neutrophil accumulation,
      and this may be one of the triggers for bone remodeling processes.

PMID- 16097234
TI  - Occlusal forces promote periodontal healing of transplanted teeth and prevent
      dentoalveolar ankylosis: an experimental study in rats.
AB  - The process of healing periodontal ligaments (PDL) after transplantation has been
      widely examined, but the mechanism for preventing dentoalveolar ankylosis is
      still unclear. In this study, we focused on the role of mechanical stimuli in
      preventing ankylosis using an animal model of tooth transplantation assessed by
      histologic observation and evaluation of proliferating PDL cells. Five-week-old
      Sprague-Dawley male rats were divided into occluded and nonoccluded groups. The
      right maxillary first molars were replanted in both groups, and histologic
      observations were carried out after one or two weeks. The proliferative activity
      of PDL cells was also examined by assessing the distribution of 5-bromo-2'
      deoxyuridine (BrdU). After two weeks in the nonoccluded group, ankylosis was
      clearly detected and PDL stricture was obvious, whereas no severe bone or root
      resorption was observed. On the other hand, the occluded group showed an enlarged
      and thickened PDL with extensive root resorption, but no ankylosis. Based on
      these findings, the replanted teeth were given a one-week healing period and then
      occlusion recovery was assessed, which resulted in decreased ankylosis and root
      resorption. The proliferative activity of PDL cells in the occluded group was
      generally higher than in the nonoccluded group. The activity of PDL cells in the
      recovery group was also higher than that of the nonoccluded group. These results
      suggest that occlusal stimuli promoted the regeneration of the PDL and prevented
      dentoalveolar ankylosis, whereas excessive initial force might cause severe root
      and bone resorption.

PMID- 16097235
TI  - A prospective long-term study of signs and symptoms of temporomandibular
      disorders in patients who received orthodontic treatment in childhood.
AB  - This investigation analyzed the influence of orthodontic treatment performed in
      childhood on the long-term development of signs and symptoms of temporomandibular
      disorders (TMDs). The original sample consisted of 50 consecutive patients (27
      girls and 23 boys) with different morphological malocclusions, who were to
      receive orthodontic treatment. Their mean age at start of treatment was 12.9
      years. Seventeen (range 15-18) years after completion of orthodontic treatment,
      40 former patients (89% of the traced subjects) completed and returned a
      questionnaire, and 31 subjects (69% of the traced subjects) were also examined
      clinically. A great majority of the participants were pleased with the result of
      the orthodontic treatment. Relapses of morphological malocclusions were very
      uncommon. The prevalence of signs and symptoms of TMD was low both before and
      after the active phase of orthodontic treatment, as well as at the long-term
      follow-up after 15 to 18 years. The incidence per year of manifest TMD requiring
      treatment was approximately 1%. The result of the present investigation supports
      the opinion that orthodontic treatment in childhood does not entail an increased
      risk to develop either signs or symptoms of TMD later in life.

PMID- 16097237
TI  - Cephalometric evaluation of nongrowing females with skeletal and dental Class II,
      division 1 malocclusion.
AB  - Studies evaluating maxillary and mandibular skeletal and dental positions and the
      vertical components of Class II patients have reported conflicting results. In
      addition, no common results have been found regarding cranial base
      configurations. However, few studies have evaluated nongrowing subjects. The aim
      of this study was to establish whether patients with skeletal and dental Class II
      division 1 malocclusion have specific craniofacial features. For this, 40
      nongrowing females were evaluated cephalometrically. Wide variations were
      observed for almost all measurements of Class II division 1 patients. However, a
      posteriorly positioned and rotated mandible, protrusive mandibular incisors, and
      an increased cranial base angle were all mean characteristics of Class II
      division 1 patients.

PMID- 16097236
TI  - Can cephalometric indices and subjective evaluation be consistent for facial
      asymmetry?
AB  - The purpose of this study was to investigate the relationship between the
      subjective evaluation of facial asymmetry and seven cephalometric indices. Ten
      orthodontists subjectively evaluated the frontal photographs of 100 subjects and
      categorized them into three categories, ie, category I--symmetrical view;
      category II--a little asymmetry not requiring treatment; and category III--marked
      asymmetry requiring treatment. Seven indices that were used to evaluate facial
      asymmetry were determined using frontal cephalographs of these patients.
      Interobserver agreement was assessed using Cohen's kappa statistic. Agreement
      among the observers for category III was higher than for categories I and II. To
      define the characteristics of each category, the cephalometric indices, which at
      least eight observers agreed on, were compared between the categories. No
      differences were found in any of the indices between categories I and II. Five
      indices showed differences between category III and the other categories. Among
      them, the distance of Me from the vertical reference line was the most relevant
      index for the subjective evaluation of facial asymmetry. When a discrepancy is
      found between skeletal measurements and a subjective evaluation, the influence of
      soft tissue structures should be considered in facial asymmetry.

PMID- 16097238
TI  - Variation in corrosion resistance of nickel-titanium wires from different
      manufacturers.
AB  - Nickel-titanium (NiTi) wires produced by various manufacturers may have different
      corrosion resistance in acidic oral environments. The purpose of this study was
      to investigate the variation during in vitro corrosion resistance of commercial
      NiTi dental orthodontic wires from different manufacturers using the fast
      electrochemical technique. The linear polarization test was used to evaluate the
      corrosion resistance, in terms of polarization resistance (Rp), of as-received
      commercial NiTi wires in acidic artificial saliva at 37 degrees C. One-way
      analysis of variance was used to analyze Rp with the wire manufacturer as the
      variable factor. Atomic force microscopy was used to analyze the three
      dimensional surface topography and roughness (Ra). Electron spectroscopy for
      chemical analysis was used to identify the chemical structure of the passive film
      on the NiTi wires. The results showed that NiTi wires from different
      manufacturers had a statistically significant difference in Rp (P < .001).
      Different surface topography was present among the tested NiTi wires, whereas the
      same surface chemical structure was observed for the tested NiTi wires. The
      surface roughness of the commercial NiTi wires with similar surface chemical
      structure does not correspond with the difference in corrosion resistance.

PMID- 16097239
TI  - Quantitative analysis of the adhesion of cariogenic streptococci to orthodontic
      metal brackets.
AB  - The aim of this study was to analyze the adhesion of cariogenic streptococci to
      orthodontic metal brackets in terms of the type of bacterial strains, the
      incubation time, and saliva coating. Two strains of Streptococcus mutans (S.
      mutans LM7 and S. mutans OMZ65) and two strains of S. sobrinus (S. sobrinus B13
      and S. sobrinus 6715) were used. Twenty metal brackets were incubated with either
      unstimulated whole saliva or phosphate-buffered saline for two hours. The
      bacterial adhesion assays were then performed by incubating the tritium-labeled
      streptococci with saliva-coated or noncoated orthodontic brackets for three, six,
      or nine hours. The results showed a characteristic binding pattern according to
      the type of bacterial strains used. S. mutans OMZ65 showed the highest amount of
      adhesion, whereas S. sobrinus B13 showed the lowest amount of adhesion.
      Generally, an extended incubation time increased the adhesion of cariogenic
      streptococci, and the amount of adhesion was the highest after nine hours of
      incubation. The saliva coating did not significantly influence the adhesion of
      bacteria. However, this saliva-mediated adhesion differed according to incubation
      time. The saliva coating tended to gradually decrease the adhesion by the
      extended incubation time, compared with the noncoated controls. This study
      indicates that each strain of cariogenic streptococci has a characteristic
      adhesion pattern and the type of bacterial strain, the incubation time, and
      saliva influenced the adhesion.

PMID- 16097240
TI  - A new one-step dental flowable composite for orthodontic use: an in vitro bond
      strength study.
AB  - A new flowable composite, Denfil Flow, has shown an acceptable shear bond
      strength for bonding orthodontic brackets, when used with an intermediate,
      unfilled, low-viscosity resin. According to the manufacturer, it also shows a
      good viscosity for use with no preliminary adhesive. This could reduce the total
      time of bonding procedure while maintaining clinically useful bond strength. The
      aim of the current research was to assess this property. Eighty extracted human
      premolars were randomly divided into four equal groups. Stainless steel brackets
      were bonded to etched enamel using (1) Denfil Flow, (2) a traditional flowable
      composite (Dyract Flow), (3) Denfil Flow composite resin and an intermediate
      liquid resin, and (4) Transbond XT adhesive. Debonding was performed with a
      shearing force. The residual adhesive on the enamel surface was evaluated using
      the adhesive remnant index. The bond strength of Denfil Flow (34.8 MPa) showed no
      significant difference with the other control groups and was clinically
      acceptable. Denfil Flow and Dyract Flow tended to display cohesive failure within
      the adhesive. Denfil Flow can be used without liquid resin to reduce the bonding
      procedure time while maintaining acceptable bond strength. Further studies are
      required to evaluate the enamel surface of the teeth after the same polishing
      procedure in the four groups.

PMID- 16097241
TI  - Phosphoric acid incorporated with acidulated phosphate fluoride gel etchant
      effects on bracket bonding.
AB  - The aim of this study was to evaluate the effects of etching with phosphoric acid
      incorporated in an acidulated phosphate fluoride (APF) gel on the bonding of a
      bracket and the loss of sound enamel. In the control group, the enamel was etched
      with 37% phosphoric acid for 30 seconds. In the experimental groups, the enamel
      was etched for 30 seconds with 37% phosphoric acid blended with 1.23% APF gel at
      various ratios (25%, 33%, 50%, 67%, and 75% APF gel). The brackets were bonded
      with Transbond XT light-cured orthodontic adhesive according to the
      manufacturer's instructions. The specimens were then treated under three
      different conditions: 37 degrees C for one hour, 37 degrees C for 24 hours, and
      thermocycling (2500 times) between 5 degrees C and 55 degrees C in deionized
      water. The shear bond strength of 10 specimens in each condition was measured and
      the results analyzed using a Tukey multiple comparison test (P = .05). The shear
      bond strength decreased significantly as the fraction of the APF gel increased in
      the experimental etchant. An apparent increase in the adhesive remnant index
      score was also observed in the large fraction of the APF gel. To minimize the
      damage of the sound enamel surface during the etching and debonding procedures, a
      mixture of phosphoric acid and an APF gel (50% and 67% APF fraction) can be used
      as an phosphoric acid etchant substitute without loss of the proper bracket bond
      strength.

PMID- 16097242
TI  - Mandibular distraction with MD-DOS device.
AB  - Distraction osteogenesis is an alternative treatment method for the correction of
      mandibular hypoplasia. In this case report, mandibular distraction with a dynamic
      osteosynthesis system (MD-DOS) was performed to gradually lengthen the mandible
      of a patient who had a severe hypoplastic mandible. The patient underwent
      intraoral bilateral mandibular distraction osteogenesis. The latency period after
      the operation was seven days. The distraction was performed three times daily for
      14 days at the rate of 0.33 mm each time. Subsequent retention was nine weeks.
      The patient's mandible was elongated successfully and a satisfactory profile and
      occlusion was achieved.

PMID- 16097243
TI  - Mostly for men.

PMID- 16097244
TI  - [Intravenous immunoglobulin therapy].
AB  - Intravenous immunoglobulins (IVIg) are therapeutic preparations of normal human
      IgG that are obtained from pools of healthy blood donors. They can be used at low
      dose in the substitutive therapy of patients with primary or secondary immune
      deficiencies, or at high dose as an immunomodulatory agent in a large number of
      autoimmune and/or systemic inflammatory diseases, particularly in hematologic or
      neurologic diseases. Tolerance to IVIg is excellent in most of the cases and the
      risk of transmission of an infectious agent is only theoretical. Mechanisms of
      action of IVIg are multiple and complicated. The development of new therapeutic
      trials in association with analyses of mechanisms of action should help to define
      new indication of IVIg therapy.

PMID- 16097245
TI  - [Compensation for medical accidents resulting from the delivery of health care].
AB  - The law of March 4, 2002 created procedure of a friendly, contradictory
      compensation and rapid in supplement of the already existing procedures. This
      device financed primarily by the social security allows the integral repair of
      the no faulty medical accidents that the medical act was carried out at the
      hospital or within a liberal framework of care. However, certain conditions are
      required so that the request is admissible: the realization of the medical act
      must be posterior to the 4/9/2001 and the undergone damage must be serious. This
      friendly procedure also allows the integral repair of the damage by the insurer
      of the third after opinion of the CRCI (Commission regionale de conciliation et
      d'indemnisation des accidents medicaux) which recognized the faulty character of
      the undergone damage.

PMID- 16097246
TI  - [Psychological follow-up of the adolescents: how to detect and help those in
      distress].

PMID- 16097247
TI  - [Adolescent psychology].
AB  - Adolescence is a transitional period dominated by puberty modifications. These
      modifications must come with a psychological work leading towards increased self
      containing from parents and also towards the choice of an own life orientation.
      In order to do so, adolescent must satisfy his needs to be able to change. This
      process will not run smoothly. The troubled adolescent will express himself with
      groans or acting out more than with words. This modus operandi is typical of that
      age. The general practitioner will be in the front line in being attentive to the
      adolescent and his parents needs.

PMID- 16097248
TI  - [Risk-taking behaviours in adolescents].
AB  - Risk-taking behaviours often reflect ambivalent ways of calling for the help of
      one's close friends and family--those who count. In spite of the suffering it
      engenders, risk-taking nevertheless has a positive side, fostering independence
      in adolescents and a search for reference points; it leads to a better self-image
      and is a means of developing one's identity. It is nonetheless painful in terms
      of the repercussions it has through the injuries, death or addiction it incurs.
      But let us not forget that the suffering in upstream, perpetuated by a complex
      relation between a society, a family structure and a life history.

PMID- 16097249
TI  - [How to deal with teenagers in general practice?].
AB  - Meeting a teenager as a general practitioner is not straightforward. Such a
      consultation has its own specific characteristics, and what is at stake goes
      beyond the apparent reason for the consultation. In order to avoid missing
      something by adopting a "wait and see" attitude in front of the uninsured
      teenagers, the author suggests the simplest ways of sticking to the four major
      objectives: ensuring self-expression, easing the relationship, improving body
      image and self esteem and increasing the range of possible solutions. A first
      series aims to expand the contents of all the consultations starting from the
      alleged reasons, the presence of a third party, the clinical examination and the
      investigative questions. A second series aims to create the conditions that help
      to get over a hurdle when a malaise has been diagnosed: confronting points of
      view, setting an appointment, strengthening the links thanks to relational tools
      and possibly directing towards the relevant health system.

PMID- 16097250
TI  - [Should psychotropic drugs be prescribed to adolescents?].
AB  - The prescription of a psychotropic drugs to an adolescent is a high-risk
      prescription that raises numerous issues, imposing a rigorous evaluation of the
      expected benefit compared with the results that could be obtained by another
      approach, and the risk of interference with the spontaneous changes inherent to
      the process of adolescence. If sedatives, anxiolytics and psychostimulants are
      proscribed, it is possible in the case of absolute necessity, to prescribe
      neuroleptics and antidepressants. In this case, the medications should be
      prescribed in efficacious doses, should be the object of negotiation with the
      adolescent and his parents, and must never be prescribed at the first
      consultation nor, in any case, consist of the sole therapeutic intervention. It
      imposes a regular follow-up of the adolescent to assess compliance and to detect
      possible suicidal ideation.

PMID- 16097251
TI  - [Family dynamics around the adolescent].
AB  - Family dynamics around the adolescent Adolescence modifies the family dynamics
      around the adolescent because adolescence comprises an unavoidable process of
      psychological separation between the subject and the parents of his childhood. On
      the adolescent side, the relations with his parents show a newer claim of
      recognition. On the parents' side, the mourning deals with several topics. The
      outcome of the crisis depends on the inner family control of anxiety and on the
      degree of differentiation of its members. Parents, grandparents and siblings have
      an important role to play in those transformations.

PMID- 16097252
TI  - [Chronic fatigue and sleep disorders in adolescents].
AB  - To be, or to feel tired, is a frequent complaint at any age, and which does not
      seem in itself to be specific of the teenager. If it frequently lies within the
      scope of an organic pathology, acute or chronic, besides while being able to be a
      revealing element for it, it is often insulated and asks a rigorous step in the
      evaluation of its various possible components. It is then important to be in an
      active listening and patient, and not in a hasty regulation of a "cosmetic"
      treatment of this subjective allegation. It is all the work of the doctor whom to
      support the emergence of the subjacent complaint whose tensions and stakes of
      adolescence post there their singularity.

PMID- 16097253
TI  - [The adolescent confronted with cancer].
AB  - In developed countries, adolescent death rate is under 1%, predominantly due to
      accidents. Amongst chronic diseases cancer has a prevalent role. A severe disease
      plays against the normal subjectivation and autonomization adolescent process. It
      leads to unbearable restrictions in being on the move with their mates, being
      proud of their body image, attending school. It increases parents' dependency and
      induces multiple treatment discomforts. Nursing team has to consider the
      adolescent as its primary interlocutor, to fulfil his demands of autonomy and to
      validate his choices, and to contribute to maintaining his links with his
      parents. Moreover, specific expressions of adolescent's needs in the field of
      pain control, body intimacy, information, schooling, sublimation's behaviours,
      sexuality, have to be recognized and satisfied.

PMID- 16097254
TI  - [Academic problems and school failure in adolescence].
AB  - Success at school increases self-esteem. Any difficulty will have consequential
      effects on the psychological health of the subject. The conditions now prevailing
      in the educational institutions (mass schooling without any individual
      orientation before the end of college) oblige the teenager to submit to teaching
      methods and to the school system. School can reveal the subject's personal
      problems (anxiety, phobia or depression), but may equally create pathology by not
      recognising the heterogeneity of individual development and differences in
      cognitive functioning. In adolescence, the ego is particularly vulnerable.
      Anything that may induce its instability can create behavioural problems
      (instability, aggressiveness, inhibition) or problems of thought (anxiety links,
      difficulties in abstraction). In order to cope with such a haemorrhage of the
      ego, the adolescent may have recourse to certain behaviours (e.g. use of drugs
      leading to dependence). So it is important the know well the links between school
      failure and behavioural problems or drug consumption because, in one way or
      another, by their sanction or by lack of motivation, these situations will lead
      very quickly to school disengagement, which in turn leads to the breakdown of the
      ego.

PMID- 16097255
TI  - [Patient education handout. Adolescents' sleep: good rules].

PMID- 16097256
TI  - [Likert's scale: clinical assessment].

PMID- 16097257
TI  - [Chronic pancreatitis].

PMID- 16097258
TI  - [Mononucleosis, diagnostic approach].

PMID- 16097259
TI  - [Parkinson's disease].

PMID- 16097260
TI  - [Cirrhosis and its complications].

PMID- 16097261
TI  - [Ankylosing spondylitis].

PMID- 16097262
TI  - [Laennec's innovative work].

PMID- 16097263
TI  - ["Therapeutic drug monitoring", a strategy for improving drug safety in child and
      adolescent psychiatry and psychotherapy].

PMID- 16097264
TI  - [Aatypical antipsychotics in child and adolescent psychiatry--indications apart
      from schizophrenia].
AB  - OBJECTIVES: Given their special receptor profile, atypical antipsychotics are
      effective in the treatment of both positive and negative symptoms. Especially the
      serotonergic affinity suggests their potential utility for the treatment of
      depressive, anxious, and obsessive-compulsive symptoms as well. Reviewed here are
      the clinical experience with, studies of, and published reports on the use of
      atypical antipsychotics in the treatment of different psychiatric disorders other
      than schizophrenia in children and adolescents. METHODS: The literature from 1998
      2004 was reviewed by means of PubMed and CurrentContents. RESULTS: In addition to
      schizophrenic symptoms, the therapeutic indications for atypical antipsychotics
      include tic disorders, bipolar affective disorders and mania, impulsiveness and
      disruptive behaviour, (auto-)aggression, and severe anorexia nervosa. Empirical
      data such as those from placebo-controlled double-blind or open-label studies in
      larger child and adolescent populations are rare. Substances are used mostly off
      label. CONCLUSIONS: Atypical antipsychotics today comprise part of the standard
      psychopharmacotherapy in child and adolescent psychiatry. They have proved to be
      effective in the treatment of schizophrenia, tic disorders, impulsiveness, (auto
      )aggression, and eating disorders.

PMID- 16097265
TI  - [Reliability of attention and verbal memory tests with normal children and
      adolescents--clinical implications].
AB  - OBJECTIVES: Neurological assessment is an intriguing tool for the
      characterisation of cognitive dysfunctions associated with childhood psychiatric
      disorders. The current article gives a short theoretical overview on
      neuropsychological functions such as attention and verbal memory. Selected
      clinical findings are summarised. Neuropsychological attention and memory tasks
      that are suited for the examination of children and adolescents are described.
      METHODS: The retest-reliability of these tasks was examined in a group of 33
      healthy children within six weeks after the original test. RESULTS: It was shown
      that reliability was generally high, albeit differing between some of the
      dependent variables. The greatest learning effects were found in younger
      children. CONCLUSIONS: The selected neuropsychological tests seem suitable for
      clinical applications such as the assessment of cognitive deficits or the
      evaluation of psychopharmacological treatment. However, age-dependent confidence
      intervals should be considered if retesting is required.

PMID- 16097266
TI  - [Can a specific assessment of attention contribute to the differential
      diagnostics of psychiatric disorders?].
AB  - OBJECTIVES: The present study examined whether or not children and adolescents
      with clinical symptoms can be differentiated according to the quantitative and
      qualitative aspects of attention. METHODS: Eighty-eight probands (ages 10-18
      years) assigned to seven ICD-10 diagnostic groups were studied for differences in
      their attention profiles. An attention task (Frankfurter Aufmerksamkeits Inventar
      -FAIR), (Moosbrugger & Oehlschlagel, 1996) validated multifold among children and
      adolescents in the domain of psychiatry was applied. This task covers three
      attention functions. Two of them are quantitative: selective attention and
      continuity of attention, while the third is qualitative: self-control. RESULTS:
      Overall, two distinctly different group-specific attention profiles evolved.
      These differed mainly in terms of self-control. Whereas all of the diagnostic
      groups studied showed relatively normal selective attention and normal continuity
      of attention, two groups exhibited substantial differences with regard to self
      control. Particularly children and adolescents with schizophrenia showed very
      poor self-control, as did those with hyperkinetic disorder, conduct disorder,
      depressive disorder, or compulsive disorder. In contrast, children and
      adolescents with eating disorders or other anxiety disorders had a high level of
      self-control. CONCLUSIONS: Thus, the self-control function was found to be a
      strong attention parameter for the differential diagnosis of a clinically
      conspicuous population of children and adolescents.

PMID- 16097267
TI  - [The decisions of indication for inpatient child and adolescent psychiatric
      treatment].
AB  - OBJECTIVES: To date there has been little empirical investigation of the
      indications for hospitalising children in child and adolescent psychiatry wards.
      Therefore we analysed the decision-making models used to establish the criteria
      for admission to child and adolescent psychiatric clinics. It is assumed that the
      clinical experience and social orientation of the specialists involved, as well
      as the standpoint of their respective institutions of health care, play a
      significant role. METHODS: The decision-making models of 71 specialists working
      in the field of in- and outpatient child and adolescent psychiatry were recorded
      using an adapted structuring process. The hypotheses were examined by comparing
      the models used by the different professional groups working in inpatient units
      and by child and adolescent psychiatrists working in private practice to the
      decision-making models used by assistant medical directors and head physicians.
      RESULTS: The factors "clinical experience" and "profession group orientation"
      were found to be of only marginal importance. Only the inpatient nursing staff
      considered social factors in arriving at an indication. The influence of such
      "setting" variables is also evident in the fact that the outpatient staff used
      more narrowly defined criteria and rated their outpatient service as being more
      sustainable than did the physicians in the inpatient departments. The criteria
      used by all professions included being a danger to oneself and others, severity
      of symptoms, the assessment of outpatient resources and efficiency, prospects of
      success, and the need for intensive treatment. CONCLUSIONS: The results of this
      study provide a basis for further research and indicate the need for additional
      discussion of the indication criteria currently in use.

PMID- 16097268
TI  - [Sleep disorders in children with attention-deficit hyperactivity disorder-
      results of a polysomnographic study].
AB  - OBJECTIVES: We report results of a polysomnographic study carried out with
      children aged 6 to 12 years with either ADHD or a sleep disorder. The study
      focussed on whether the sleep structure and architecture of n = 36 ADHD children
      with and without sleep disorders differed from that of either n=15 children with
      sleep disorders or n=87 children without sleep disorders. Moreover, we assessed
      whether there was an increased risk for co-morbid sleep-related breathing
      disorders among ADHD children. METHODS: All children underwent polysomnography in
      a paediatric clinic. Principal variables of the sleep structure and architecture
      as well as cardiorespirographic measures were analysed. RESULTS: Our findings
      demonstrate that sleep problems in children with ADHD seem to be unspecific
      concurrent symptoms since the sleep structure of sleep-disordered ADHD children
      and children with sleep disorders was similar. Only minor differences were found
      between non-sleep-disturbed ADHD children and healthy children without sleep
      problems. CONCLUSIONS: We conclude that sleep problems in ADHD are independent co
      morbid symptoms without any pathogenetic relationship to vigilance functions in
      ADHD. The cardiorespirographic analyses showed that a subgroup of ADHD children
      with sleep problems may be at increased risk for co-morbid sleep-related
      breathing disorder. This finding is potentially important for differential
      diagnostic considerations in ADHD.

PMID- 16097269
TI  - [Early intervention family therapy in drug-dependent adolescents, young adults,
      and their mothers--effect sizes and intraindividual change indices in
      completers].
AB  - OBJECTIVES: An outpatient program of medication-free family therapy for
      polysubstance drug-dependent adolescents and young adults is evaluated on the
      basis of multiple criteria. The family therapy provided is brief systemic early
      intervention. METHODS: The evaluation was based on intent-to-treat data:
      prospective, naturalistic, pre-post. Eighty-six families (86 patients in the
      early stage of drug dependency, 76 mothers, 57 fathers, 36 siblings) enrolled.
      Individual multi-criteria rates of respondence are determined by means of five
      goal criteria (addiction status, family function, symptom severity, psychosocial
      integration, and therapy satisfaction) documented via patient self-reports and
      expert ratings. Individual outcome values are reported for drug-dependent
      patients and participating mothers. RESULTS: Therapy was completed by 72% of the
      families participating. Of the index patients who completed therapy, 73% showed a
      significant intra-individual improvement in their addiction status. Both drug
      dependent patients and their mothers improved with regard to other goal criteria.
      CONCLUSIONS: In a program of early-intervention outpatient therapy, adolescents
      and young adults diagnosed in an early stage of polysubstance drug-dependency and
      still in contact with their families of origin, will improve.

PMID- 16097270
TI  - [Social and individual determinants of tobacco consumption in early adolescence].
AB  - OBJECTIVES: We examined the structure of individual and social determinants of
      tobacco consumption in early adolescence. METHODS: Participants were drawn from a
      longitudinal study of a birth cohort of originally 384 children at risk for
      psychopathology. At the age of 15 years, adolescents completed self-report
      questionnaires measuring their tobacco consumption, smoking-related attitudes
      (self-efficacy and outcome expectancies), and the smoking behaviour of their
      friends and parents. RESULTS: About 60% of the 15-year olds reported ever having
      used tobacco, while nearly 16% reported that they smoked daily. Both smoking
      related self-efficacy and peer smoking were most strongly related to early use of
      tobacco by males and females. Adolescents with a low level of self-efficacy and a
      large number of friends who smoke were at the greatest risk. While peer smoking
      influenced both, adolescent smoking and smoking-related attitudes, parental
      smoking exerted only a minor direct effect on tobacco use among 15-year olds.
      CONCLUSIONS: The smoking level and smoking-related attitudes during early
      adolescence are strongly influenced by the smoking habits of one's peers.

PMID- 16097271
TI  - Validation of the holyoake codependency index.
AB  - Some clinicians working with families with alcohol or other drug problems
      continue to use the codependency model to guide their practice despite the
      limited empirical support for this approach. Research into codependency has been
      hampered by the lack of psychometrically sound instruments. The Holyoake
      Codependency Index (HCI; G. E. Dear & C. M. Roberts, 2000) is a 13-item self
      report measure of codependent traits that has previously shown adequate to high
      reliability, initial evidence of construct validity, and an internal structure
      that is consistent across samples. In the 4 studies reported here, the internal
      structure of the HCI was confirmed using confirmatory factor analysis, and
      further evidence of construct validity was found in that the HCI subscales showed
      meaningful associations with other psychological and demographic variables.

PMID- 16097272
TI  - The dynamics of self-esteem in adults over a 6-month period: an exploratory
      study.
AB  - In this exploratory study, the authors examined the dynamics of self-esteem in 8
      adults over a 6-month period. Each participant (M age = 29.4 years, SD = 7.9, SEM
      = 2.8) completed a single item from the Physical Self Inventory (G. Ninot, M.
      Fortes, & D. Delignieres, 2001) using a 10-cm visual analog scale (horizontal
      line), twice a day between 7:00 and 9:00 a.m. and between 7:00 and 9:00 p.m. Time
      series analyses, including autocorrelation and autoregressive integrated moving
      average (ARIMA) procedures, showed that global self-esteem dynamics were neither
      stable, stationary, nor random. The ARIMA procedures indicated that this
      perceived dimension functioned as a moving average (0, 1, 1) without a
      significant constant, thus suggesting a short-term dynamic adjustment. This
      pattern is a typical signature of a complex system submitted to several
      constraints and not an indication of personality trait or state.

PMID- 16097273
TI  - Gender differences in dominance and affiliation during a demanding interaction.
AB  - Evolution theory predicts that in social situations, men will show more
      behavioral dominance, whereas women will show more behavioral affiliation. To
      ensure maximum ecological validity, observation in a real-life situation that
      calls for uniform behavior is the strongest test. To reduce bias because of
      stereotyping within observers, the author used molecular behavioral observations,
      in which the verbal and nonverbal behavior of 10 men and 10 women was observed in
      an executive job selection assessment center where they were actual applicants.
      Men showed more dominance, especially head shaking, sitting in a closed posture,
      and using closed questions and directive remarks. Women showed more affiliation,
      especially in frequency of laughing, sitting in an open posture, and posing open
      questions.

PMID- 16097275
TI  - The prediction of stress by values and value conflict.
AB  - The authors investigated the relationships among stress, values, and value
      conflict. Data collected from 400 people working in a variety of companies in
      Flanders indicated that the values of openness to change, conservation, self
      transcendence, and self-enhancement were important predictors of stress.
      Participants open to change reported less stress, whereas participants who had
      high scores on conservation, self-enhancement, and self-transcendence perceived
      more stress. People who reported high value conflict also experienced more
      stress. Separate analyses for men and women showed that there were gender
      differences in the relationships observed between the 4 value types and stress.
      These data have noteworthy theoretical and practical implications.

PMID- 16097274
TI  - Children's, adolescents', and young adults' reward allocations to hypothetical
      siblings and fairness judgments: effects of actor gender, character type, and
      allocation pattern.
AB  - The authors studied the reward allocation patterns, reasoning, and fairness
      judgments of 112 participants at 4 grade levels: kindergarten, 3rd grade, 9th
      grade, and college. Three story characters (an oldest, the most productive, and
      the physically disadvantaged) were depicted as siblings of the same gender,
      either sisters or brothers, who poured lemonade at a school picnic.
      Kindergartners' pattern of reward allocations indicated the use of an equality
      and productivity-based equity rule, whereas most of the older participants
      integrated considerations of both productivity and physical disadvantage in their
      allocations. Reasoning data were generally consistent with the allocation
      patterns. Reward allocations differed significantly by the gender of the
      characters, and fairness ratings differed significantly by the gender of the
      characters and the gender of the participant. Conclusions discuss the increasing
      coordination and consideration of more than one claim to the reward with
      development.

PMID- 16097276
TI  - Factors influencing limb survival after femoropopliteal reconstruction.

PMID- 16097277
TI  - Carcinoma of the breast.

PMID- 16097278
TI  - Solid tumor chemotherapy with mitomycin C.

PMID- 16097279
TI  - The effect of Q-switched ruby laser radiation on dermal tattoo pigment in man.

PMID- 16097280
TI  - Radical thoracico-abdominal adrenalectomy and lymphadenectomy. Treatment for
      feminizing carcinoma.

PMID- 16097281
TI  - Protection against the toxic action of oxygen at high pressure. Effect of sodium
      succinate on Ehrlich ascites cells.

PMID- 16097282
TI  - Subphrenic abscess secondary to salmonellosis.

PMID- 16097283
TI  - Salmonella infection in ruptured abdominal aortic aneurysm.

PMID- 16097284
TI  - Hemobilia following percutaneous needle biopsy of the liver.

PMID- 16097285
TI  - An unusual case of hemobilia. Hepatic tuberculosis with hemorrhage.

PMID- 16097286
TI  - A combined method for diagnosis in malignant jaundice.

PMID- 16097287
TI  - The effects of congestion on certain liver tissue constituent weights.

PMID- 16097288
TI  - Roentgenographic evaluation of experimental intraperitoneal abscess.

PMID- 16097289
TI  - Intracholecystic abscess.

PMID- 16097290
TI  - Cholecystocolonic fistula.

PMID- 16097291
TI  - Production of diarrhea in dogs prepared with a gallbladder-colon fistula.

PMID- 16097292
TI  - Primary carcinoma of the gallbladder. A review of 78 patients.

PMID- 16097293
TI  - Structure and size of canine common bile duct.

PMID- 16097294
TI  - Small-bowel infarction due to intramural hematoma during anticoagulant therapy.

PMID- 16097295
TI  - Silicone fluid in the prevention of intestinal adhesions.

PMID- 16097296
TI  - Congenital absence of vermiform appendix.

PMID- 16097297
TI  - Chronic in situ studies of the electrical activity of the small intestine.

PMID- 16097298
TI  - Duodenal varices.

PMID- 16097299
TI  - "In vivo" staining of the parathyroid glands and pancreas.

PMID- 16097300
TI  - A ten-year experience with ureteroileostomy.

PMID- 16097301
TI  - Fibromuscular hyperplasia of the internal carotid artery.

PMID- 16097303
TI  - Needle tracheostomy--further evaluation.

PMID- 16097302
TI  - Antibiotic topical spray applied in a simulated combat wound.

PMID- 16097305
TI  - Extraosseous chondrosarcoma of the maxilla.

PMID- 16097304
TI  - Mycobacterial ("Buruli") ulcer in a Peace Corps worker.

PMID- 16097306
TI  - Pelvic lymphocyst: diagnosis and management.

PMID- 16097307
TI  - Isolated hypogastric artery aneurysm. Review and report of three cases.

PMID- 16097308
TI  - Phospholipids and nucleic acid in pulmonary secretions.

PMID- 16097309
TI  - The abdominal mass in the patient with tuberous sclerosis. Surgical implications
      and report of a case.

PMID- 16097310
TI  - The infraclavicular venipuncture. Value in various clinical situations including
      central venous pressure monitoring.

PMID- 16097311
TI  - Determination of urinary metabolites of phosalone, methidathion, and IBP after
      oral administration and dermal application to rats.

PMID- 16097312
TI  - Association between lifetime cadmium intake and cadmium concentration in
      individual urine.

PMID- 16097314
TI  - Acute and chronic toxicity test methods for Nematostella vectensis Stephenson.

PMID- 16097313
TI  - Comparative toxicity of pokeweed (Phytolacca americana) extracts to invasive
      snails (Viviparus georgianis) and fathead minnows (Pimephales promelas) and the
      implications for aquaculture.

PMID- 16097315
TI  - Effect of cadmium on fin regeneration in the freshwater Fish, Oreochromis
      mossambicus.

PMID- 16097316
TI  - Behavioral responses of rainbow trout Oncorhynchus mykiss to sublethal toxicity
      of a model mixture of heavy metals.

PMID- 16097317
TI  - Estrogenic activity of treated municipal effluent from seven sewage treatment
      plants in Victoria, Australia.

PMID- 16097318
TI  - Metal accumulation and ecophysiological effects of distillery effluent on
      Potamogeton pectinatus L.

PMID- 16097319
TI  - Residues and toxicity of esfenvalerate and permethrin in water and sediment, in
      tributaries of the Sacramento and San Joaquin rivers, California, USA.

PMID- 16097320
TI  - Acute toxicity of imidacloprid and fipronil to a nontarget aquatic insect,
      Simulium vittatum Zetterstedt cytospecies IS-7.

PMID- 16097321
TI  - Acute toxicity of alpha-cypermethrin on tilapia (Oreochromis niloticus L.)
      larvae.

PMID- 16097322
TI  - PH dependent toxicity of pyridine raffinate to a common duckweed, Lemna minor L.

PMID- 16097323
TI  - Bromate residues in some popular baked products in relation to the sustained
      antibromate campaign in Nigeria.

PMID- 16097324
TI  - Dioxin formation during combustion of nonchloride plastic, polystyrene and its
      product.

PMID- 16097325
TI  - Treatment train for site remediation at a petrochemicals-contaminated site within
      a petroleum refinery.

PMID- 16097326
TI  - Accidental discharge of brodifacoum baits in a tidal marine environment: a case
      study.

PMID- 16097327
TI  - Pesticide residues in surface water from irrigation-season monitoring in the San
      Joaquin Valley, California, USA.

PMID- 16097328
TI  - Distribution, fate, and effects of 14C-DDT in model ecosystems simulating
      tropical Kenyan freshwater environments.

PMID- 16097329
TI  - Distribution of organochlorine pesticides in urban soil from Beijing, People's
      Republic of China.

PMID- 16097330
TI  - Polycyclic aromatic hydrocarbon pollution in sediments of the Canakkale
      (Dardanelles) strait, Turkey.

PMID- 16097331
TI  - Concentration and distribution of several pesticides applied to paddy fields in
      water and sediment, from Sugao Marsh, Japan.

PMID- 16097332
TI  - Distribution of polychlorinated biphenyls in different depths of soil from a
      polluted area in the People's Republic of China.

PMID- 16097333
TI  - Mercury contamination in mushroom samples from Tokat, Turkey.

PMID- 16097334
TI  - Mercury in an assortment of processed and unprocessed seafood samples.

PMID- 16097335
TI  - Methylmercury and total mercury in sediments collected from the East China Sea.

PMID- 16097336
TI  - Distribution and concentration of trace metals in tissues of different fish
      species from the Atlantic coast of Western Africa.

PMID- 16097337
TI  - Heavy metals in the oyster Crassostrea corteziensis from Urias lagoon, Mazatlan,
      Mexico, associated with different anthropogenic discharges.

PMID- 16097338
TI  - Lead, cadmium, copper, manganese, and zinc in wetland waters of Victoria Lake
      basin, East Africa.

PMID- 16097339
TI  - Efficiently measuring recognition performance with sparse data.
AB  - We examine methods for measuring performance in signal-detection-like tasks when
      each participant provides only a few observations. Monte Carlo simulations
      demonstrate that standard statistical techniques applied to a d' analysis can
      lead to large numbers of Type I errors (incorrectly rejecting a hypothesis of no
      difference). Various statistical methods were compared in terms of their Type I
      and Type II error (incorrectly accepting a hypothesis of no difference) rates.
      Our conclusions are the same whether these two types of errors are weighted
      equally or Type I errors are weighted more heavily. The most promising method is
      to combine an aggregate d' measure with a percentile bootstrap confidence
      interval, a computer-intensive nonparametric method of statistical inference.
      Researchers who prefer statistical techniques more commonly used in psychology,
      such as a repeated measures t test, should use gamma (Goodman & Kruskal, 1954),
      since it performs slightly better than or nearly as well as d'. In general, when
      repeated measures t tests are used, gamma is more conservative than d': It makes
      more Type II errors, but its Type I error rate tends to be much closer to that of
      the traditional .05 alpha level. It is somewhat surprising that gamma performs as
      well as it does, given that the simulations that generated the hypothetical data
      conformed completely to the d' model. Analyses in which H--FA was used had the
      highest Type I error rates. Detailed simulation results can be downloaded from
      www.psychonomic.org/archive/Schooler-BRM-2004.zip.

PMID- 16097340
TI  - Parametric and nonparametric bootstrap methods for meta-analysis.
AB  - In a meta-analysis, the unknown parameters are often estimated using maximum
      likelihood, and inferences are based on asymptotic theory. It is assumed that,
      conditional on study characteristics included in the model, the between-study
      distribution and the sampling distributions of the effect sizes are normal. In
      practice, however, samples are finite, and the normality assumption may be
      violated, possibly resulting in biased estimates and inappropriate standard
      errors. In this article, we propose two parametric and two nonparametric
      bootstrap methods that can be used to adjust the results of maximum likelihood
      estimation in meta-analysis and illustrate them with empirical data. A simulation
      study, with raw data drawn from normal distributions, reveals that the parametric
      bootstrap methods and one of the nonparametric methods are generally superior to
      the ordinary maximum likelihood approach but suffer from a bias/precision
      tradeoff. We recommend using one of these bootstrap methods, but without applying
      the bias correction.

PMID- 16097341
TI  - Exploring function estimators as an alternative to regression in psychology.
AB  - Most forms of regression analysis make assumptions about the relationships
      between the variables being modeled. As a consequence, it can be difficult to
      know which form of analysis is most appropriate for a given data set. In this
      article, we explore the idea that function estimators might provide a better
      alternative in many situations. Function estimators discover the best function to
      link dependent and independent variables, no matter what form this takes. Four
      studies demonstrate that one type of function estimator (a neural network) not
      only performs the same tasks as linear regression and nonlinear regression, but
      often performs these tasks better and with more flexibility. Moreover, neural
      networks allow a useful secondary analysis in which useful groups of people can
      be identified. We recommend that function estimators be used in preference to
      regression-based techniques for many analyses. The Matlab script used to write
      this article may be downloaded from www.psychonomic.org/archive/.

PMID- 16097342
TI  - Determining the significance of scale values from multidimensional scaling
      profile analysis using a resampling method.
AB  - Although multidimensional scaling (MDS) profile analysis is widely used to study
      individual differences, there is no objective way to evaluate the statistical
      significance of the estimated scale values. In the present study, a resampling
      technique (bootstrapping) was used to construct confidence limits for scale
      values estimated from MDS profile analysis. These bootstrap confidence limits
      were used, in turn, to evaluate the significance of marker variables of the
      profiles. The results from analyses of both simulation data and real data suggest
      that the bootstrap method may be valid and may be used to evaluate hypotheses
      about the statistical significance of marker variables of MDS profiles.

PMID- 16097343
TI  - Exploring item and higher order factor structure with the Schmid-Leiman solution:
      syntax codes for SPSS and SAS.
AB  - To ease the interpretation of higher order factor analysis, the direct
      relationships between variables and higher order factors may be calculated by the
      Schmid-Leiman solution (SLS; Schmid & Leiman, 1957). This simple transformation
      of higher order factor analysis orthogonalizes first-order and higher order
      factors and thereby allows the interpretation of the relative impact of factor
      levels on variables. The Schmid-Leiman solution may also be used to facilitate
      theorizing and scale development. The rationale for the procedure is presented,
      supplemented by syntax codes for SPSS and SAS, since the transformation is not
      part of most statistical programs. Syntax codes may also be downloaded from
      www.psychonomic.org/archive/.

PMID- 16097344
TI  - TETCORR: a computer program to compute smoothed tetrachoric correlation matrices.
AB  - Although many programs exist for computing tetrachoric correlations, these
      programs typically lack one or more of the following features: (1) efficient
      processing of a large number of variables and computing of a matrix of
      coefficients; (2) a matrix-smoothing capability; (3) an accurate, reliable
      computing algorithm; (4) the ability to handle missing data; and (5) nominal
      cost. TETCORR, which combines an algorithm developed by Brown (1977) with
      starting values obtained from Divgi (1979a) for more efficient computation, was
      created to address these and other user concerns.

PMID- 16097345
TI  - N-watch: a program for deriving neighborhood size and other psycholinguistic
      statistics.
AB  - This article describes a Windows program that enables users to obtain a broad
      range of statistics concerning the properties of word and nonword stimuli,
      including measures of word frequency, orthographic similarity, orthographic and
      phonological structure, age of acquisition, and imageability. It is designed for
      use by researchers in psycholinguistics, particularly those concerned with
      recognition of isolated words. The program computes measures of orthographic
      similarity on line, either with respect to a default vocabulary of 30,605 words
      or to a vocabulary specified by the user. In addition to providing standard
      orthographic neighborhood measures, the program can be used to obtain information
      about other forms of orthographic similarity, such as transposed-letter
      similarity and embedded-word similarity. It is available, free of charge, from
      the following Web site: http://www.maccs.mq. edu.au/colin/N-Watch/.

PMID- 16097346
TI  - Dismal: a spreadsheet for sequential data analysis and HCI experimentation.
AB  - Dismal is a spreadsheet that works within GNU Emacs, a widely available
      programmable editor. Dismal has three features of particular interest to those
      who study behavior: (1) the ability to manipulate and align sequential data, (2)
      an open architecture that allows users to expand it to meet their particular
      needs, and (3) an instrumented and accessible interface for studies of human
      computer interaction (HCI). Example uses of each of these capabilities are
      provided, including cognitive models that have had their sequential behavior
      aligned with subject's protocols, extensions useful for teaching and doing HCI
      design, and studies in which keystroke logs from the timing package in Dismal
      have been used.

PMID- 16097348
TI  - Social dominance orientation, prejudice, and discrimination: a new computer-based
      method for studying discriminatory behaviors.
AB  - A number of studies have shown that the scale of social dominance orientation
      (SDO), used to measure the degree of preference for inequality among social
      groups, is a predictive measure of social and political attitudes toward
      stigmatized outgroups. However, the relationship between SDO and discrimination
      has received little attention. The main goal of this study was to assess the
      validity of a new computer-based method used to measure discriminatory behaviors
      in a laboratory setting. An additional goal was to test the mediating role of
      prejudice in the relation between SDO and discrimination. The results provide a
      first validation of this new method and demonstrate that the effect of SDO on
      discrimination is mediated by prejudice.

PMID- 16097347
TI  - Laboratory behavioral measures of impulsivity.
AB  - Previous research and theory have conceptualized impulsivity as a multifaceted
      construct that requires multiple modes of measurement for accurate assessment.
      This article describes a software package that includes four paradigms for
      measuring multiple and unique aspects of impulsivity. Specifically, four tasks
      are described: (1) the two choice impulsivity paradigm, (2) the single key
      impulsivity paradigm, (3) the GoStop impulsivity paradigm, and (4) the time
      paradigm. These tasks measure processes related to the capacity to tolerate delay
      for reward, to inhibit an already initiated response, and to estimate the passage
      of time. These processes have been found to be important to the understanding of
      impulsive behaviors. The programs are flexible and allow the experimenter to
      manipulate a number of parameters related to delay-reward contingencies, timing,
      performance feedback/payment, and data output variables. Manipulation of these
      parameters makes the paradigms scalable to a wide range of ability levels and
      appropriate for samples ranging from children to adults. The four paradigms in
      this software package are available at no cost and can be obtained by contacting
      the corresponding author.

PMID- 16097349
TI  - An on-line task for contrasting auditory processing in the verbal and nonverbal
      domains and norms for younger and older adults.
AB  - Contrasting linguistic and nonlinguistic processing has been of interest to many
      researchers with different scientific, theoretical, or clinical questions.
      However, previous work on this type of comparative analysis and experimentation
      has been limited. In particular, little is known about the differences and
      similarities between the perceptual, cognitive, and neural processing of
      nonverbal environmental sounds and that of speech sounds. With the aim of
      contrasting verbal and nonverbal processing in the auditory modality, we
      developed a new on-line measure that can be administered to subjects from
      different clinical, neurological, or sociocultural groups. This is an on-line
      task of sound to picture matching, in which the sounds are either environmental
      sounds or their linguistic equivalents and which is controlled for potential task
      and item confounds across the two sound types. Here, we describe the design and
      development of our measure and report norming data for healthy subjects from two
      different adult age groups: younger adults (18-24 years of age) and older adults
      (54-78 years of age). We also outline other populations to which the test has
      been or is being administered. In addition to the results reported here, the test
      can be useful to other researchers who are interested in systematically
      contrasting verbal and nonverbal auditory processing in other populations.

PMID- 16097350
TI  - The Walter Reed palm-held psychomotor vigilance test.
AB  - This field-portable reaction time test and analysis software run on devices using
      the Palm operating system. It is designed to emulate a test and commercial device
      widely used in sleep deprivation, shift work, fatigue, and stimulant drug
      research but provides additional capabilities. Experimental comparisons with the
      standard commercial device in a 40-hour total sleep deprivation study show it to
      be comparably sensitive to selected experimental variables. A Pocket PC
      compatible version is under developement.

PMID- 16097351
TI  - Use of interactive voice response (IVR) technology in health research with
      children.
AB  - This article reports on the feasibility of using interactive voice response (IVR)
      technology to obtain daily reports of attitudes toward alcohol and tobacco use
      among children 9-13 years of age. Two studies were conducted. The first was an
      investigation of the use of IVR technology to obtain daily data from a sample of
      primary school children over a period of 8 weeks. The second was an extension of
      the research to a large sample of primary and secondary school children in urban
      and rural areas who provided daily data over a 4-week period. Retention and
      compliance rates comparable to those obtained with adults were evident in both
      studies, supporting the feasibility of this technology with children. The results
      are discussed in relation to the benefits of this methodology for health
      research, particularly for studies of sensitive topics conducted with children
      and adolescents.

PMID- 16097352
TI  - Low-cost data transfer from a questionnaire to standard software using a barcode
      pen.
AB  - Computer-aided transfer of questionnaire data simplifies the analysis of
      questionnaires. We present a solution based on an inexpensive barcode pen and its
      decoder, the software tool Barcode Wizard included in CorelDRAW, and a self
      developed application written using Microsoft Visual Basic for Applications. The
      barcode may be provided on the questionnaire or on a transparency. Error
      correction is done by means of two different procedures. The present solution can
      be applied while looking over the completed questionnaire and thus allows time
      saving, economic, and precise data transfer from the completed questionnaire
      directly into computer software.

PMID- 16097353
TI  - Reliability of a portable head-mounted eye tracking instrument for schizophrenia
      research.
AB  - Smooth pursuit eye movement (SPEM) abnormalities are some of the most
      consistently observed neurophysiological deficits associated with genetic risk
      for schizophrenia. SPEM has been traditionally assessed by infrared or video
      oculography using laboratory-based fixed-display systems. With growing interest
      in using SPEM measures to define phenotypes in large-scale genetic studies, there
      is a need for measurement instruments that can be used in the field. Here we test
      the reliability of a portable, head-mounted display (HMD) eye movement recording
      system and compare it with a fixed-display system. We observed comparable, modest
      calibration changes across trials between the two systems. The between-methods
      reliability for the most often used measure of pursuit performance, maintenance
      pursuit gain, was high (ICC = 0.96). This result suggests that the portable
      device is comparable with a lab-based system, which makes possible the collection
      of eye movement data in community-based and multicenter familial studies of
      schizophrenia.

PMID- 16097354
TI  - The delayed trigger voice key: an improved analogue voice key for
      psycholinguistic research.
AB  - Many researchers rely on analogue voice keys for psycholinguistic research.
      However, the triggering of traditional simple threshold voice keys (STVKs) is
      delayed after response onset, and the delay duration may vary depending on
      initial phoneme type. The delayed trigger voice key (DTVK), a stand-alone
      electronic device that incorporates an additional minimum signal duration
      parameter, is described and validated in two experiments. In Experiment 1,
      recorded responses from a nonword naming task were presented to the DTVK and an
      STVK. As compared with hand-coded reaction times from visual inspection of the
      waveform, the DTVK was more accurate than the STVK, overall and across initial
      phoneme type. Rastle and Davis (2002) showed that an STVK more accurately
      detected an initial [s] when it was followed by a vowel than when followed by a
      consonant. Participants' responses from that study were presented to the DTVK in
      Experiment 2, and accuracy was equivalent for initial [s] in vowel and consonant
      contexts. Details for the construction of the DTVK are provided.

PMID- 16097355
TI  - Nonequivalence of on-line and paper-and-pencil psychological tests: the case of
      the prospective memory questionnaire.
AB  - There is growing evidence that Internet-mediated psychological tests can have
      satisfactory psychometric properties and can measure the same constructs as
      traditional versions. However, equivalence cannot be taken for granted. The
      prospective memory questionnaire (PMQ; Hannon, Adams, Harrington, Fries-Dias, &
      Gibson, 1995) was used in an on-line study exploring links between drug use and
      memory (Rodgers et al., 2003). The PMQ has four factor-analytically derived
      subscales. In a large (N = 763) sample tested via the Internet, only two factors
      could be recovered; the other two subscales were essentially meaningless. This
      demonstration of nonequivalence underlines the importance of on-line test
      validation. Without examination of its psychometric properties, one cannot be
      sure that a test administered via the Internet actually measures the intended
      construct.

PMID- 16097356
TI  - A PDA-based system for online recording and analysis of concurrent events in
      complex behavioral processes.
AB  - This article outlines how a Palm- or Newton-based PDA (personal digital
      assistant) system for online event recording was used to record and analyze
      concurrent events. We describe the features of this PDA-based system, called the
      FIT-System (flexible interface technique), and its application to the analysis of
      concurrent events in complex behavioral processes--in this case, anesthesia work
      processes. The patented FIT-System has a unique user interface design allowing
      the user to design an interface template with a pencil and paper or using a
      transparency film. The template usually consists of a drawing or sketch that
      includes icons or symbols that depict the observer's representation of the
      situation to be observed. In this study, the FIT-System allowed us to create a
      design for fast, intuitive online recording of concurrent events using a set of
      41 observation codes. An analysis of concurrent events leads to a description of
      action density, and our results revealed a characteristic distribution of action
      density during the administration of anesthesia in the operating room. This
      distribution indicated the central role of the overlapping operations in the
      action sequences of medical professionals as they deal with the varying
      requirements of this complex task. We believe that the FIT-System for online
      recording of concurrent events in complex behavioral processes has the potential
      to be useful across a broad spectrum of research areas.

PMID- 16097357
TI  - A portable, unobtrusive device for videorecording clinical interactions.
AB  - Recording and analyzing real-time interactions in clinical settings is important
      for basic and applied research in psychology and other disciplines. Investigators
      frequently have used simple audiotaping procedures to record these encounters
      (e.g., Roter, Geller, Bernhardt, Larson, & Doksum, 1999), but videorecording is
      increasingly viewed as more reliable and valid, because it captures the full
      range of complex and interdependent verbal and nonverbal behaviors that occur in
      an interaction. This article describes a system designed to videotape clinical
      interactions in a manner that can be moved in and out of different clinical rooms
      to preserve flexibility in its use. Data are presented to demonstrate that the
      system is unobtrusive during the interaction, yet fully compatible with
      institutional review board guidelines to protect human participants' privacy and
      freedom to control the recording process.

PMID- 16097358
TI  - Nonlinear, near photo-realistic caricatures using a parametric facial appearance
      model.
AB  - A mathematical model previously developed for use in computer vision applications
      is presented as an empirical model for face space. The term appearance space is
      used to distinguish this from previous models. Appearance space is a linear
      vector space that is dimensionally optimal, enables us to model and describe any
      human facial appearance, and possesses characteristics that are plausible for the
      representation of psychological face space. Randomly sampling from a multivariate
      distribution for a location in appearance space produces entirely plausible
      faces, and manipulation of a small set of defining parameters enables the
      automatic generation of photo-realistic caricatures. The appearance space model
      leads us to the new concept of nonlinear caricatures, and we show that the
      accepted linear method for caricature is only a special case of a more general
      paradigm. Nonlinear methods are also viable, and we present examples of
      photographic quality caricatures, using a number of different transformation
      functions. Results of a simple experiment are presented that suggest that
      nonlinear transformations can accurately capture key aspects of the caricature
      effect. Finally, we discuss the relationship between appearance space,
      caricature, and facial distinctiveness. On the basis of our new theoretical
      framework, we suggest an experimental approach that can yield new evidence for
      the plausibility of face space and its ability to explain processes of
      recognition.

PMID- 16097359
TI  - Establishing and maintaining an operant research facility with brushtail possums
      (Trichosurus vulpecula).
AB  - The common brushtail possum (Trichosurus vulpecula) is a readily accessible
      marsupial that has been shown to adapt relatively well to captivity. The aim of
      this paper is to outline the husbandry procedures, experimental equipment, and
      methodologies used successfully within our possum colony since 1995.

PMID- 16097360
TI  - A portable, low-resistance puff topography instrument for pulsating, high-flow
      smoking devices.
AB  - A smoking topography instrument appropriate for pulsating high flow rate smoking
      devices, such as the narghile water pipe, has been developed and tested.
      Instrument precision and repeatability was determined using a digitally
      controlled smoking machine, and the added draw resistance due to the topography
      instrument was measured over the range of expected puff flow rates. The maximum
      error in any topography variable was found to be less than 5%. The instrument was
      successfully demonstrated in a pilot field study of 30 volunteer narghile
      smokers. The pilot study yielded an average smoker puff volume, duration, and
      interpuff interval of 0.531, 2.47 sec, 16.28 sec, respectively.

PMID- 16097361
TI  - Hypertensive heart disease.
AB  - Left ventricular hypertrophy (LVH) and diastolic dysfunction (CHF-D) are the
      early manifestations of cardiovascular target organ damage in patients with
      arterial hypertension and signify hypertensive heart disease. Identification of
      hypertensive heart disease is critical, as these individuals are more prone to
      congestive heart failure, arrhythmias, myocardial infarction and sudden cardiac
      death. Regression of left ventricular (LV) mass with antihypertensive therapy
      decreases the risk of future cardiovascular events. The goal of antihypertensive
      therapy is to both lower blood pressure (BP) and interrupt BP-independent
      pathophysiologic processes that promote LVH and CHF-D. The purpose of this review
      is to summarize current and emerging approaches to the pathophysiology and
      treatment of hypertensive heart disease.

PMID- 16097362
TI  - Metabolic syndrome and cardiac disease in Japanese men: applicability of the
      concept of metabolic syndrome defined by the National Cholesterol Education
      Program-Adult Treatment Panel III to Japanese men--the Tanno and Sobetsu Study.
AB  - Results of a 6-year follow-up study were used to determine whether the concept of
      and the criteria for metabolic syndrome as defined by the National Cholesterol
      Education Program-Adult Treatment Panel III (NCEP-ATP III) can be applied to
      Japanese men for prediction of the occurrence of cardiac disease. The subjects
      were 808 men who underwent mass health check-ups in 1993 and who were not on
      medication for hypertension, diabetes or hyperlipidemia. Individuals who had
      hypertriglyceridemia, hypo-high density lipoprotein (HDL) cholesterolemia, high
      blood pressure, and/or high fasting plasma glucose levels were identified on the
      basis of the NCEP-ATP III criteria. Not in conformity with the NCEP-ATP Ill,
      however, a cut-off value of 85 cm was used for waist girth as an indicator of
      abdominal obesity. The subjects who had 3 or more risk factors were judged as
      having metabolic syndrome. The proportion of subjects having metabolic syndrome
      was 25.3%. In the 6-year follow-up study, cardiac disease occurred in 11.7% of
      the subjects in the metabolic syndrome group and in 6.7% of the subjects in the
      non-metabolic syndrome group. Results of regression analysis using Cox's
      proportional hazards model showed that subjects in the metabolic syndrome group
      had a 2.2-times greater risk of developing cardiac disease than did subjects in
      the non-metabolic syndrome group. The concept of metabolic syndrome as defined in
      the NCEP-ATP III was therefore considered to be useful for predicting the
      occurrence of cardiac disease in Japanese men.

PMID- 16097363
TI  - Comparison of the effects of valsartan and felodipine on plasma leptin and
      insulin sensitivity in hypertensive obese patients.
AB  - Aim of this study was to compare the effect of valsartan and felodipine on blood
      pressure (BP), plasma leptin (L), insulin sensitivity and plasma norepinephrine
      (NE) in obese hypertensive patients. Ninty-six obese patients (body mass index
      [BMI] > or = 30 kg/m2) with mild to moderate essential hypertension (diastolic
      blood pressure [DBP] > 90 and < 110 mmHg, as evaluated with an appropriately
      sized cuff) aged 31-60 years, were randomized to a valsartan (80 mg/day for 16
      weeks; n = 48) or felodipine (5 mg/day for 16 weeks; n = 48) treatment group
      after a 2-week wash-out period. After the first 4 weeks of treatment there was a
      titration with dose-doubling in non responder patients (DBP > 90 mmHg). At the
      end of the placebo period and of active treatment period, BP and BMI were
      evaluated and a venous sample was drawn at the same hour in the morning to
      evaluate plasma L and NE. Insulin resistance index (HOMA-IR) was calculated. No
      dietary advice was prescribed. Both valsartan and felodipine significantly
      decreased BP values (-19.3/15 mmHg and -18.9/13.6 mmHg, respectively p < 0.001
      vs. placebo), with no difference between treatments. However, felodipine
      increased plasma NE (+124 pg/ml, +38.2%, p < 0.05 vs. placebo and < 0.01 vs.
      valsartan) and had no effect on L, body weight and HOMA-IR index, while valsartan
      did not modify NE and produced a significant reduction in L (-3.7 ng/ml, -10.1%,
      p < 0.05 vs. placebo), BMI (-1.7 kg/m2, -4.7%, p < 0.01 vs. placebo) and HOMA-IR
      index (-1.6, -20%, p < 0.05 vs. placebo). These results suggest that in
      hypertensive obese subjects, treatment with valsartan might offer an advantage
      over treatment with felodipine, since valsartan may help to improve obesity
      related disorders in addition to lowering BP.

PMID- 16097364
TI  - Association of dopamine beta-hydroxylase polymorphism with hypertension through
      interaction with fasting plasma glucose in Japanese.
AB  - Dopamine-beta-hydroxylase (DBH) catalyzes the conversion of dopamine to
      norepinephrine and is released from sympathetic neurons into the circulation.
      Several lines of evidence, including the finding of elevated plasma DBH activity
      in essential hypertension, suggest an important role of DBH in hypertension.
      Recently, a novel polymorphism (-1021C/T) in the 5' flanking region of the DBH
      gene has been shown to account for 35-52% of the variation in plasma DBH
      activity. We therefore investigated the possible association between the DBH 
      1021C/T polymorphism and hypertension in a large Japanese population. Moreover,
      because the development of hypertension is considered to be due at least partly
      to gene-environmental interactions, we also investigated the possible
      interactions between the DBH -1021C/T polymorphism and environmental factors.
      Consequently, we found a significant interaction between the DBH -1021C/T
      polymorphism and fasting plasma glucose (FPG) in the association with
      hypertension. CC homozygotes showed a steeper increase in probability of
      hypertension with FPG than T allele carriers. We also found a marginally
      significant trend suggesting the presence of an interaction between the DBH 
      1021C/T polymorphism and FPG in the association with blood pressure. Consistent
      with the presence of the interaction, we found that a 19 bp sequence containing
      the DBH -1021C/T polymorphism includes two palindromic non-canonical E boxes
      separated by 5 bps, and closely resembles the glucose response element of the L
      type pyruvate kinase gene. These findings could be helpful in conducting further
      molecular and biological studies on the relationship among glucose metabolism,
      the sympathetic nervous system, and hypertension.

PMID- 16097365
TI  - Interaction between amlodipine and simvastatin in patients with
      hypercholesterolemia and hypertension.
AB  - 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are often
      prescribed in association with antihypertensive agents, including calcium
      antagonists. Simvastatin is an HMG-CoA reductase inhibitor that is metabolized by
      the cytochrome P450 (CYP) 3A4. The calcium antagonist amlodipine is also
      metabolized by CYP3A4. The purpose of this study was to investigate drug
      interactions between amlodipine and simvastatin. Eight patients with
      hypercholesterolemia and hypertension were enrolled. They were given 4 weeks of
      oral simvastatin (5 mg/day), followed by 4 weeks of oral amlodipine (5 mg/day) co
      administered with simvastatin (5 mg/day). Combined treatment with simvastatin and
      amlodipine increased the peak concentration (C(max)) of HMG-CoA reductase
      inhibitors from 9.6 +/- 3.7 ng/ml to 13.7 +/- 4.7 ng/ml (p < 0.05) and the area
      under the concentration-time curve (AUC) from 34.3 +/- 16.5 ng h/ml to 43.9 +/-
      16.6 ng h/ml (p < 0.05) without affecting the cholesterol-lowering effect of
      simvastatin. This study is the first to determine prospectively the
      pharmacokinetic and pharmacodynamic interaction between amlodipine and
      simvastatin.

PMID- 16097366
TI  - Haplotype-based case-control study revealing an association between the
      adrenomedullin gene and proteinuria in subjects with essential hypertension.
AB  - Adrenomedullin (AM) has various physiological actions on the cardiovascular
      system, including vasodilatation, diuresis, natriuresis, inhibition of
      aldosterone secretion, and increases of the cardiac output, all of which cause
      hypotension. Since AM plays a role in the pathophysiology of vascular diseases,
      genes controlling AM might be involved in the development and etiology of
      essential hypertension (EH). However, there have been few studies examining the
      relationship between the AM gene and hypertension. The aims of this study were to
      genotype some of the genetic markers for the human AM gene in Japanese subjects,
      and via a haplotype-based case-control study, assess the association between and
      the AM gene and EH or its risk factors, such as hyperlipidemia, renal damage, and
      proteinuria. We genotyped 205 EH patients and 210 age-matched normotensive (NT)
      individuals for two single nucleotide polymorphisms of rs4399321, rs7944706 and a
      microsatellite polymorphism located approximately 5,400 base pairs downstream of
      the 3' end of the human AM gene. The overall distribution in each variant and
      haplotype did not significantly differ between the two groups. However, after
      dividing the groups into those subjects with and without proteinuria, the
      haplotype analysis revealed a positive association. In conclusion, a possible
      mutation linked to the haplotype may indicate a genetic predisposition for
      proteinuria in EH.

PMID- 16097367
TI  - Predictors of undiagnosed renal artery stenosis among Japanese patients with risk
      factors of atherosclerosis.
AB  - Atherosclerotic renal artery stenosis (ARAS) is a significant cause of end stage
      renal dysfunction (ESRD) among the elderly. Although early detection of ARAS and
      induction of adequate treatment could reduce the incidence of ESRD, there have
      been few reports about parameters predictive of ARAS among Japanese. In this
      study, we investigated the clinical indicators that predict ARAS among Japanese
      with risk factors of atherosclerosis (> 40 years of age plus hypertension,
      dyslipidemia or diabetes mellitus). After eliminating the patients who had
      already been diagnosed with renal artery stenosis, 202 patients were enrolled.
      The renal arteries of all 202 patients were evaluated by magnetic resonance
      arteriography (MRA), and the stenoses with > 50% reduction in diameter at the
      ostium of the renal artery were defined as ARAS. MRA detected ARAS in 42 patients
      (31 hemilateral and 11 bilateral). Between the patients with and without ARAS
      there was no significant difference in gender distribution, detection of
      abdominal vascular bruits or smoking habit. The prevalences of diabetic,
      hypertensive and cerebrovascular comorbidity were also not significantly
      different. The mean blood pressure, body mass index and total serum cholesterol
      values were similar between the two groups. However, age, pulse pressure, serum
      uric acid, serum creatinine, amount of urinary protein, and coronary artery
      comorbidity were significantly higher, while estimated creatinine clearance was
      significantly lower in the patients with ARAS than in those without ARAS. A high
      prevalence of hypertensive retinopathy was also noted among patients with ARAS.
      Multivariate analysis revealed that older age and renal impairment were
      independent predictors of ARAS in Japanese patients with atherosclerotic risk
      factors.

PMID- 16097368
TI  - Different effects of imidapril and enalapril on aminopeptidase P activity in the
      mouse trachea.
AB  - It has been reported that the incidence of angiotensin-converting enzyme (ACE)
      inhibitor-related dry cough is significantly less with the ACE inhibitor
      imidapril than with the ACE inhibitor enalapril in hypertensive patients.
      Bradykinin (BK) in the trachea is believed to play some role in this adverse
      effect. The present study was undertaken to evaluate the effects of imidapril and
      enalapril on the activity of aminopeptidase P (APP), one of the BK-metabolizing
      enzymes, in the mouse trachea. Imidapril (0.5 mg/kg) or enalapril (0.5 mg/ kg)
      was given orally to mice once daily for 7 days. Drug concentrations and APP
      activity in the trachea were determined at the end of the experiment. Active
      metabolites (imidaprilat and enalaprilat), but not parent drugs (imidapril and
      enalapril) were detected in the trachea after a repeated dose for 7 days. Tissue
      concentrations of imidaprilat and enalaprilat did not significantly differ. The
      APP activity in the trachea did not significantly change after the 7th dose of
      imidapril. However, the enzyme activity was significantly inhibited after the
      final dose of enalapril. Thus, the present study showed that enalapril, but not
      imidapril inhibited the airway APP activity during repeated dosing. This finding
      is compatible with previous reports that the incidence of dry cough is lower with
      imidapril than with enalapril, and with the hypothesis that the dry cough induced
      by ACE inhibitors may be related to accumulation of BK in the trachea.

PMID- 16097369
TI  - Protective effect of antioxidant ebselen (PZ51) on the cerebral cortex of stroke
      prone spontaneously hypertensive rats.
AB  - An increase in reactive oxygen species has been shown to play a role in
      perpetuating hypertension and cerebral injury in stroke-prone spontaneously
      hypertensive rats (SHRsp). Lipid peroxidation in the cerebral cortex is much more
      intense in SHRsp after establishment of severe hypertension as compared to that
      in normotensive Wistar-Kyoto rats (WKY). Cortical neurons from SHRsp are more
      vulnerable to hypoxia and hyponutritional conditions. We sought to investigate
      whether long-term administration of seleno-glutathione peroxidase mimic ebselen
      (PZ51) would have a protective effect on cortical neurons in SHRsp, and, if so,
      the possible mechanisms of this effect. Twenty-two 8-week-old SHRsp were
      randomized into a PZ51 group and control group. Age-matched WKY were used as
      normal controls. We examined the levels of malonaldehyde (MDA) and nitric oxide
      (NO) in the cerebral cortex (CC) homogenate, detected the three isoforms of
      nitric oxide synthase (NOS) by Western blotting, and examined cortical neurons by
      transmission electron microscopy. The results showed that PZ51 treatment
      significantly decreased both MDA and NO in the CC, inhibited inducible nitric
      oxide synthase (iNOS) protein expression, and alleviated the damage to cortical
      neurons compared to the findings for the control group. In conclusion, the
      present study showed that PZ51 administration suppressed lipid peroxidation and
      inhibited iNOS protein expression in CC homogenate, and it was suggested that
      these mechanisms may play a role in the protective effects of PZ51 on cortical
      neurons of SHRsp.

PMID- 16097371
TI  - Estrogen reduces angiotensin II-induced acceleration of senescence in endothelial
      progenitor cells.
AB  - The interaction among estrogen, angiotensin II (Ang II), and oxidative stress in
      endothelial progenitor cells (EPCs) remains unknown. We therefore investigated
      the potential effect of estrogen on Ang II-induced EPC oxidative stress and
      senescence in EPCs. EPCs were isolated from peripheral blood and characterized.
      Both reverse transcription (RT)-polymerase chain reaction (PCR) and Western
      blotting were used to assess gp91phox and angiotensin type 1 receptor (AT1R)
      expression. Immunofluorescence of nitrotyrosine provided evidence of
      peroxynitrite formation. Our data indicate that Ang II increased the expression
      of gp91phox mRNA and protein, and these effects were attenuated by 17beta
      estradiol (E2). The exposure of cultured EPCs to Ang II (100 nmol/l)
      significantly accelerated the rate of senescence compared to that in control
      cells during 14 days in culture as determined by acidic beta-galactosidase
      staining, and this effect was significantly inhibited by E2 (p < 0.01). Because
      cellular senescence is critically influenced by telomerase, which elongates
      telomeres, we measured telomerase activity by using a PCR-ELISA-based assay. Ang
      II significantly diminished telomerase activity, although the effect was
      significantly reduced by pre-treatment with E2 (p < 0.01). Because we previously
      demonstrated that both the up-regulation of gp91phox and the acceleration of
      cellular senescence in Ang II-stimulated EPCs could be abolished by pre-treatment
      with the AT1R- specific antagonist, valsartan, we also explored the effect of
      estrogen on AT1R expression. Ang II increased AT1R mRNA and protein expression,
      and these increases were prevented by E2, suggesting that AT1R may at least
      partially mediate the inhibitory effect of E2 on Ang II-induced acceleration of
      senescence in EPCs. In conclusion, estrogen reduces Ang II-induced acceleration
      of senescence in EPCs partially through down-regulation of AT1R expression.

PMID- 16097370
TI  - Pioglitazone lowers systemic asymmetric dimethylarginine by inducing
      dimethylarginine dimethylaminohydrolase in rats.
AB  - Peroxisome proliferator activated receptor-gamma (PPARgamma) ligands increase
      nitric oxide (NO) production and reduce systemic blood pressure. Asymmetric
      dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor
      degraded by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which has
      two isoforms, DDAH-I and -II. In order to elucidate the mechanism whereby
      PPARgamma ligands affect NO metabolism, their effects on the DDAH-ADMA pathway
      were investigated. Six-week-old male Wister-Kyoto rats (WKY) and spontaneously
      hypertensive rats (SHR) were maintained with or without pioglitazone (PIO), a
      PPARgamma ligand. After 4 weeks, serum ADMA levels and urinary daily NO excretion
      were analyzed. Tissue DDAH expression was examined by real-time polymerase chain
      reaction (PCR), immunoblotting, and immunohistochemistry. The results showed that
      PIO decreased serum ADMA and increased urinary NO excretion in both WKY and SHR.
      Also in both strains, the expression level of DDAH-II in the kidney was increased
      at transcriptional levels, although the DDAH-I level was unaffected. PIO lowered
      blood pressure in SHR, but not in WKY. We also demonstrated that PIO induced DDAH
      II protein expression in Marbin-Dubin Canine Kidney (MDCK) cells, a renal tubular
      cell line. In conclusion, a PPARgamma ligand was here found to increase NO
      production partly by upregulating tissue DDAH-II expression and decreasing
      systemic ADMA levels. This mechanism constitutes a direct action on renal tubular
      cells, but is less likely to be responsible for the blood pressure-lowering
      effects of PPARgamma ligands. Since ADMA is one of the risk factors for
      cardiovascular events, this study provides compelling evidence that PPARgamma
      ligands have the potential for reducing cardiovascular risks.

PMID- 16097372
TI  - Identification of quantitative trait loci for cardiac hypertrophy in two
      different strains of the spontaneously hypertensive rat.
AB  - Cardiac hypertrophy and left ventricular hypertrophy are known to be
      substantially controlled by genetic factors. As an experimental model, we
      undertook genome-wide screens for cardiac mass in F2 populations bred from the
      stroke-prone spontaneously hypertensive rats (SHRSP) and normal spontaneously
      hypertensive rats (SHR) and Wistar Kyoto rats (WKY) of a Japanese colony. Two F2
      cohorts were independently produced: F2(SHRSP x WKY) (110 male and 110 female
      rats) and F2(SHR x WKY) (151 male rats). The ratio of heart weight to body weight
      (Hw/Bw) was evaluated at 12 months of age in F2(SHRSP x WKY) after salt-loading
      for 7 months, and at around 15 weeks of age in F2(SHR x WKY) who had been fed a
      normal rat chow diet. Subsequent to an initial screen with 251 markers in
      F2(SHRSP x WKY) male progeny, 170 and 161 markers were selected and characterized
      in F2(SHRSP x WKY) female progeny and F2(SHR x WKY) male progeny, respectively.
      Markers from four chromosomal regions showed suggestive or significant linkage to
      Hw/Bw. The strongest and the most consistent linkage was found in the vicinity of
      D3Mgh16 on rat chromosome (RNO) 3 (a maximal log of the odds score reached 4.0 to
      6.6 across the F2 populations studied). In the other three regions on RNO6, RNO10
      and RNO13, the degree of linkage was more prominent in either males or females.
      These data provide solid evidence for a "principal" RNO3 quantitative trait loci
      regulating Hw/Bw in SHRSP and SHR, and also suggest the possible presence of
      sexual dimorphism in regard to genetic susceptibility for cardiac hypertrophy.

PMID- 16097373
TI  - [Obesity, strengthen the prevention and treatment campaign nationwide].

PMID- 16097374
TI  - [National ranking tests, why and how?].

PMID- 16097375
TI  - [Obesity management knowledge, attitudes and practices of general practitioners
      in southeastern France; results of a telephone survey].
AB  - OBJECTIVE: To describe the current knowledge, attitudes, and practices of French
      general practitioners (GPs) in the field of child and adult overweight and
      obesity management. METHODS: A cross-sectional telephone survey interviewed a
      sample of 600 GPs, representative of the population of private GPs in
      southeastern France. A three-part questionnaire assessed attitudes and opinions
      about overweight and obesity, knowledge and training in this field, and practices
      (diagnostic methods, standard weight loss objectives, types of counseling).
      RESULTS: Most GPs (90.2%) regarded obesity as a disease requiring long-term
      management (99.5%), and 79% agreed that managing these problems is part of their
      role. Nevertheless, 58 and 66% did not feel they perform this role effectively
      for their adult patients and for children and teenagers, respectively.
      Approximately 30% had negative attitudes towards overweight and obese patients.
      Most practices followed the guidelines relatively closely. Nevertheless, 60%
      often set weight loss objectives more demanding than guidelines call for; neither
      food diaries nor nutritional education were used systematically; 55% often
      forbade children and teenagers to eat specific foods. DISCUSSION: These results,
      which were based on GPs' declarations, revealed the existence of a gap between
      theory and practice in the field of obesity management: GPs felt responsible for
      but ineffective in this management. Their feelings of ineffectiveness may be
      furthered by the underlying disagreement in the attitudes of practitioner and
      patient towards weight problems and the ensuing difficulties in their
      relationship.

PMID- 16097376
TI  - Prevalence of methadone injection in three Swiss cities.
AB  - OBJECTIVE: Intravenous methadone is associated with increased risk of morbidity
      and mortality. A previous report from a methadone center in Fribourg,
      Switzerland, found a high prevalence (43%) of patients who injected oral
      methadone. We therefore wished to assess the prevalence of methadone injection
      among patients in oral methadone programs in 3 other Swiss cities--Lausanne,
      Geneva, and La Chaux-de-Fonds. METHOD: Subjects were randomly selected and
      interviewed by assistant psychologists who were not on the staff of the study
      centers. Participation was voluntary and anonymous. RESULTS: 164 patients
      participated in the study (n = 58 in Lausanne, 52 in Geneva, and 54 in La Chaux
      de-Fonds). The prevalence of methadone injection was low (5%) and did not differ
      significantly between the cities. DISCUSSION: Less liberal policies cannot
      explain the lower prevalence of methadone injection in these three centers than
      in Fribourg. The high prevalence of methadone injection there is probably related
      to its separate methadone injection program: patients in oral methadone programs
      may be more likely to injection methadone when other patients authorized to do
      so. IN CONCLUSION: Although the 5% prevalence of methadone injection found in the
      3 cities surveyed is low, it is not negligible. These results suggest that
      information on the risks associated with injection of methadone syrup should be
      provided to all methadone maintenance. This information is especially necessary
      when maintenance therapy is provided in the same center, or city as injectable
      methadone maintenance.

PMID- 16097377
TI  - [Logistical regression of success factors in the former internship examination
      for medical students].
AB  - INTRODUCTION: The French competitive internship examination for medical students
      was replaced in 2004 by a national-ranking exam. The profile of students
      successful at the internship exam, although more or less stereotypical, was never
      methodically analyzed. AIMS: To determine the factors that influenced success in
      the internship exam. METHODS: Records of 242 students from four successive
      entering classes (1989-1992) at the Saint-Etienne Faculty of Medicine underwent
      logistical regression analysis. Factors studied were: gender; occupation of the
      head of household; details about their General Certificate of Education test (age
      attest, core subject, overall grade); repeating any first-cycle medical studies
      (PCEM1); PCEM1 grade; number of certificates resat at the end-of-year make-up
      session or the following year during second-cycle medical studies (DCEM), known
      as "debts"; and the ranking obtained in the five faculty certificate tests deemed
      representative of the overall competitive test and on the clinical and
      therapeutic summary certificate (CSCT). RESULTS: The 95 students (59%) who did
      not take the internship exam differed from those who did. The former typically:
      (1) were older when they began studying medicine (p = 0.003); (2) had passed the
      General Certificate of Education with the lowest or next lowest pass levels (p =
      0.023); (3) re-did their PCEM1 studies (p = 0.001); (4) were ranked in the lower
      two-thirds of their PCEM1 class (p = 0.001); (5) had more PCEM1 certificates to
      resit during DCEM (p = 0.007); (6) were ranked in the lower two-thirds of their
      class for the certificates (including the CSCT) (p < 0.001). Of the 147 students
      who did take the internship exam, 102 (69%) passed. Logistical regression
      identified three predictive factors in their success: (1) took the General
      Certificate of Education at an average or younger than average age (adjusted odds
      ratio (OR) 7.79, confidence interval (CI) 95% [1.59-38.13]); (2) had at most one
      "debt" (adjusted OR 16.51 [1.88-144.78); (3) ranked in the top third of their
      class for certificates (including the CSCT) (adjusted OR 7.84 [2.42-25.41]).
      CONCLUSION: Our study objectively confirmed that consistent work and effective
      learning strategies, acquired early during education and applied throughout
      medical studies, strongly promoted success in the previous internship exam. It is
      likely--but should be verified--that medical students who choose this strategy of
      constant effort will also do best on the new national-ranking examination.

PMID- 16097378
TI  - [The choice of a medical career in a population of 600 second-cycle French
      medical students preparing the national-ranking exam].
AB  - OBJECTIVES: To analyse the choice of career of a sample of second-cycle French
      medical students following the implementation of the recent national-ranking exam
      (NRE). METHODS: All the medical students registered in a cycle of conferences to
      prepare for the NRE filled-in a self-administered, anonymous, questionnaire in
      Paris and the provinces during the university year 2004. The items concerned the
      choice of career, according to the NRE discipline selected, and the mobility
      required for the success of the project. RESULTS: Six hundred students were
      included in the study; 398 were women (66%) and 202 were men (34%), with a mean
      age of 23.2 +/- 6 years (21-29). Two hundred were at the end of their first cycle
      (33%) and 400 at the end of their third cycle (67%). Two hundred came from the
      provinces (33%) and 400 from Paris. Regarding the disciplines selected, medical
      specialisation predominated (36.2%) followed by surgical specialisation (15.5%)
      and general medicine (11.3%); psychiatry ranked lowest (4.5%). Psychiatry ranked
      lowest in Paris (4.8%) and gynaecology-obstetrics in the provinces (3.5%).
      Regarding geographical mobility, 83.3% of Parisians and 16.8% of provincials
      refused the idea of completing their third cycle anywhere other than in their
      area of origin. CONCLUSION: The NRE permitted the integration of general medicine
      among all the other clinical specialisations. Surgery retained a place of choice
      among the disciplines selected by the students. However, many Parisian students
      will be obliged to take on a residency in a hospital other than their original
      university hospital.

PMID- 16097379
TI  - [Predictability of the results of the 2004 French national-ranking exam].
AB  - OBJECTIVE: To assess the individual predictability of success for undergraduate
      medical students taking the French national-ranking examination (examen classant
      national [NRE]) in June 2004. METHODS: In total, 86 students in Rouen were
      classified according to RNE scores. We used the Spearman rank test [rs] to
      correlate to the RNE score each student's previous test results during the
      medical curriculum: written exams (first two years of medical classes), clinical
      skill tests (third- and fourth-year) and the clinical and therapeutic synthesis
      certificate (CSCT), and the northwest region official RNE practice test. Each
      student's ECN rank was then predicted by a regression formula. RESULTS: Written
      exam (r5 = 0.35), third- and fourth-year clinical skill (r(s) = 0.62), CSCT (r(s)
      = 0.49) and regional practice test (r(s) = 0.56) scores were strongly and
      significantly associated with the RNE classification. Of the 59 students who took
      all tests, 12 students (20.3%) diverged from the regression model: three students
      obtained a national classification substantially better than expected, nine
      ranked substantially lower than expected. CONCLUSION: Test results during the
      undergraduate medical curriculum in a cohort of undergraduate medical students
      were strongly predictive of the RNE results. An identifiable group of students
      with unstable results could benefit from targeted teaching and individual
      support. The effect of knowledge of their individual position before the RNE
      remains to be assessed.

PMID- 16097380
TI  - [Acute nonalcoholic nonbiliary pancreatitis. Difficulties in diagnosis and
      possibility of nicotine toxicity].
AB  - INTRODUCTION: The possibility of nicotine toxicity, although rare, should be
      considered in cases of acute edematous pancreatitis. CASE: A 30-year-old woman
      was hospitalized to identify the cause of an initial episode of acute edematous
      pancreatitis. The observation of native anti-DNA and antiphospholipid antibodies
      suggested lupus pancreatitis and/or an antiphospholipid syndrome, both
      subsequently ruled out. The final diagnosis was nicotine poisoning induced by the
      combination of a nicotine patch and tobacco smoking. CONCLUSION: Although a
      nicotine patch has never been reported in connection with an episode of acute
      pancreatitis before, this case suggests that such an event might be a rare
      complication of an overdose of nicotine.

PMID- 16097381
TI  - [Agauria salicifolia intoxication].
AB  - INTRODUCTION: Several plants of the Ericaceae family produce grayanotoxins, which
      can poison humans. The best-known of these intoxications involves the eating of
      "mad honey" contaminated by rhododendron nectar grayanotoxins. The authors report
      a case of poisoning due to ingestion of Agauria salicifolia, an Ericaceae species
      endemic in the Mascarene Islands. CASE: A 28-year-old woman mistakenly ingested a
      herbal tea made with leaves of this plant. Symptoms were characteristic of
      grayanotoxin intoxication, with vomiting, arterial hypotension and bradycardia.
      The patient was managed in an intensive care unit and recovered within a few
      hours after symptomatic treatment of the low blood pressure and the severe
      digestive disorders. CONCLUSION: This case underlines that ingestion of some
      plants can be toxic.

PMID- 16097382
TI  - [Dural arteriovenous fistula, a rare cause of congestive heart failure in elderly
      patients].
AB  - INTRODUCTION: Arteriovenous fistula is a curable cause of high output congestive
      heart failure. CASE: An 89-year-old woman was hospitalized for acute heart
      failure. The presence of a continuous murmur in the right carotid artery
      suggested an arteriovenous fistula. Arteriography showed a dural fistula of the
      right lateral sinus and confirmed the diagnostic hypothesis. Embolization was
      ruled out because of the patient's clinical condition, but medical treatment
      produced a satisfactory outcome. DISCUSSION: Clinical diagnosis of an
      arteriovenous fistula is based on the characteristic murmur. We report the first
      case of a dural arteriovenous fistula manifested by congestive heart failure in
      an elderly patient.

PMID- 16097383
TI  - [Streptococcus pyogenes and Mycoplasma pneumoniae: pulmonary coinfection or
      serologic artefact?].
AB  - INTRODUCTION: How should Mycoplasma pneumoniae seroconversion be interpreted in a
      patient with community-acquired Streptococcus pyogenes pneumonia? CASE: A 21-year
      old man with cerebral palsy was hospitalized with acute pneumonia and fever. The
      bronchoalveolar lavage fluid contained Streptococcus pyogenes, and serological
      testing for Mycoplasma pneumoniae was positive. At 4 weeks, measurements of anti
      M. pneumoniae and antistreptolysin O antibodies were positive. DISCUSSION: Two
      hypotheses should be considered: the patient has either a coinfection of S.
      pyogenes and M. pneumoniae or a nonspecific antibody response during a severe S.
      pyogenes infection.

PMID- 16097384
TI  - [Is dialysis efficient in the prevention of ionic contrast agent-induced
      nephropathy?].
AB  - A FREQUENT AND EXPENSIVE PROBLEM: Ninety percent of contrast media nephrotoxicity
      (CMN) occur in patients with pre-existing kidney failure. Its aggravation may
      require early chronic dialysis. PREVENTIVE MEASURES: CMN prophylaxis is important
      in these patients. Pre- and post-hydration, with infusion of isotonic saline
      solution or sodium bicarbonate, and reduction of contrast medium (CM) volume to
      the strict minimum are essential for preventing CM-induced kidney failure. THE
      INTEREST OF PROPHYLACTIC HEMODIALYSIS AND HEMOFILTRATION: An interesting approach
      in preventing CMN is the early elimination of the CM with dialysis techniques.
      Preventive hemodialysis does not reduce the risk of CMN, but hemofiltration has
      shown significant efficacy in a population of patients with kidney failure. THE
      INTEREST OF IMMEDIATE HEMODIALYSIS IN CHRONIC HEMODIALYSIS PATIENTS: Although
      nephrotoxicity is no longer a problem in patients undergoing chronic
      hemodialysis, CM, especially in high-dose injections, may be responsible for
      fluid and electrolyte abnormalities and/or volemic expansion. No data yet justify
      a conclusion that a hemodialysis session immediately after injection of a CM in
      chronic dialysis patients might be helpful.

PMID- 16097385
TI  - [Hypertension and Alzheimer's disease].
AB  - Case-control transversal studies have suggested the existence of an association
      between low blood pressure and Alzheimer's disease, although there is some doubt
      on the cause to effect relationship. A drop in blood pressure preceding the onset
      of dementia has been evoked but never confirmed. Longitudinal studies, with long
      term follow-up on the existence of hypertension during middle-age, have
      demonstrated a significant increase in the risk of developing Alzheimer's disease
      in cohorts of hypertensive patients compared to normotensive subjects. The
      potential benefit of preventive treatment with antihypertensive drugs in
      decreasing the risk of Alzheimer's disease has not been confirmed in clinical
      trials. The hypothesis of the formation of a cerebrovascular disease that would
      combine with the neuropathological lesions has been evoked, raising doubts on the
      diagnostic criteria used to define Alzheimer's disease. The novel concept that
      vascular risk factors could directly induce the formation of neuropathological
      lesions is interesting but warrants confirmation.

PMID- 16097386
TI  - [National-ranking exams (NRE) in 2004. Students, faculties and university
      hospitals are awaiting the results].
AB  - The results of the 2004 National-Ranking Exams supply interesting but preliminary
      information. Its intended goal is to rank the students, but it also provides
      qualitative and quantitative data about students, the success rates of various
      university teaching and research units (UFR - unite de formation et de
      recherche), the ranking for each of the 11 possible specialties, student
      mobility, and the relative desirability of the University Hospital Centres. In
      these first ranking exams, the medical and surgical specialties appear to be
      selected by students with the highest ranks, while less good scores lead to
      public health, occupational medicine. On an individual level, nonetheless, all
      combinations are seen.

PMID- 16097387
TI  - [The link between molecules produced by the adipose tissue, obesity and
      atherothrombosis].
AB  - Obesity is associated with increased risk of cardiovascular morbidity.
      Biologically active molecules produced by adipose tissue constitute a critical
      link between obesity and cardiovascular complications. Adipose tissue has
      recently been recognized to be an important endocrine organ that controls energy
      metabolism. It also secretes adipocytokines, which can modify vascular responses,
      and antifibrinolytics, including plasminogen activator inhibitor 1, which favors
      fibrin accumulation, and proinflammatory cytokines, which facilitate the
      inflammatory response. Here we review new advances in our understanding of the
      mechanisms linking the endocrine activity of adipose tissue to vascular risk.

PMID- 16097388
TI  - [Cystic dystrophy of the duodenal wall and heterotopic pancreas].

PMID- 16097389
TI  - Reliability of bulky DNA adducts measurement by the nuclease P1 32P-post
      labelling technique.
AB  - The aim was to assess the reliability of bulky DNA adducts measurement by means
      of the 32P-post-labelling assay. The research design consisted of an intramethod
      reliability study. Buffy coats from 41 subjects were used to obtain two aliquots
      of 1-5 microg DNA for each subject; bulky DNA adducts were measured using the
      nuclease P1 32P-post-labelling technique. The reliability of the measurement was
      assessed by means of the intraclass correlation coefficient (ICC), the
      distribution of the differences between the two measurements and the limits of
      agreement. The estimated ICC was 0.977, with a 95% confidence interval between
      0.921 and 0.977. The limits of agreement were +/- 0.44 (DNA adducts per 10(8)
      nucleotides). Only three subjects had differences lying out of such limits. Bulky
      DNA adduct levels measured by the 32P-post-labelling technique showed good
      reliability. Only one measurement is needed to use DNA adducts as a biomarker of
      exposure and, possibly, cancer risk. Besides, as a validation analysis, 32P-post
      labelling measurements can be repeated in only 20-30% of samples.

PMID- 16097390
TI  - Urinary metabolites of workers exposed to nitrotoluenes.
AB  - Nitrotoluenes are important intermediates in the chemical industry. 2,6
      Dinitrotoluene (26DNT), 2,4-dinitrotoluene (24DNT) and 2-nitrotoluene (2NT) are
      carcinogenic in animals and possibly carcinogenic in humans. Thus, it is
      important to develop methods to biomonitor workers exposed to such chemicals. The
      authors have monitored the air and urine metabolite levels for a group of workers
      in China exposed to 24DNT, 26DNT, 2NT and 4-nitrotoluene (4NT). The metabolites
      2,4-dinitrobenzylalcohol (24DNBAlc), 2-amino-4-nitrobenzoic acid (2A4NBA), 4
      amino-2-nitrobenzoic acid (4A2NBA) and 2,4-dinitrobenzoic acid (24DNBA) resulting
      from exposure to 24DNT were found in 89, 88, 91 and 78% of the exposed workers,
      respectively. The metabolites 2,6-dinitrobenzylalcohol (26DNBAlc) and 2,6
      dinitrobenzoic acid resulting from 26DNT exposure were found in 99 and 86% of the
      exposed workers, respectively. Quantitatively, 2A4NBA, 4A2NBA and 26DNBAlc were
      the major metabolites. The nitrobenzoic acids were the major metabolites
      resulting from exposure to 2NT and 4NT and were present in 96 and 73% of the
      exposed workers, respectively. Air concentrations of DNT and 2NT did not
      correlate with the levels of metabolites in the urine. In conclusion, the
      dinitrobenzyl alcohols and aminonitrobenzoic acids determined in the urine
      provided a good marker for recently absorbed dose and were intrinsically related
      to the bioactivation and detoxification pathways of DNT. Air measurements were
      not a good measure to predict internal exposure.

PMID- 16097391
TI  - Identification of stool proteins in C57BL/6J mice by two-dimensional gel
      electrophoresis and MALDI-TOF mass spectrometry.
AB  - Gastrointestinal disease is a major cause of mortality in humans and animals, and
      the detection of disease-associated protein in stool is an established diagnostic
      method in this context. Yet, no data currently exists about the protein
      composition of mammalian faeces. Using a newly developed two-dimensional (2D) gel
      method, 28 of the most abundant proteins in murine faeces were identified.
      Mammalian faeces contains protein from multiple species (from the individual,
      from gastrointestinal bacteria, from food, etc.). Yet, it was found that the
      majority of mouse stool proteins were of mouse origin, with a minority of
      proteins being derived from food (in particular soybean glycinin and conglycinin)
      and bacteria (flagellin). Most mouse proteins were proteases and saccharidases
      derived from the exocrine pancreas. In addition, two unexpected mouse proteins
      were identified: one was a newly described mucin-like protein from intestinal
      goblet cells (FcgammaBP); the other was the secreted form of carbonic anhydrase
      (type VI) from salivary gland. The data suggest that 2D analysis of faecal
      protein is likely to provide meaningful information about the physiological stage
      of the gastrointestinal tract. Compared with studies based on biopsies, faecal
      protein analysis may reduce the number of laboratory animals, and might also
      allow quicker bridging from animal studies to humans, where biopsy material is
      more difficult to obtain and is less relevant for general practice use.

PMID- 16097392
TI  - DNA damage (comet assay) and 8-oxodGuo (HPLC-EC) in relation to oxidative stress
      in the freshwater bivalve Unio tumidus.
AB  - The relationships between DNA damage and oxidative stress in the digestive gland,
      gills and haemocytes of the freshwater bivalve Unio tumidus were investigated.
      Two markers of genotoxicity were measured: DNA breaks by means of the comet
      assay, and oxidative DNA lesions by means of 8-oxo-7,8-dihydro-2'-deoxyguanosine
      (8-oxodGuo) measured using high-performance liquid chromatography (HPLC) coupled
      to electrochemical detection. Lipid peroxidation was evaluated by measuring
      malondialdehyde (MDA) tissue levels. Effects were studied after exposure of
      bivalves for 6 days to benzo[a]pyrene (B[a]P) (50 and 100 microg l(-1)) and
      ferric iron (20 and 40 mg l(-1)), applied alone or in combination. Lipid
      peroxidation in the digestive gland and gills resulted from exposure to Fe3+ or
      B[a]P whatever the concentrations tested. DNA oxidatively formed lesions were
      induced in the two tissues at a higher level after B[a]P exposure than after Fe3+
      treatment. No significant dose-response relationship was found with the two
      compounds and no synergistic effect was observed between Fe3+ and B[a]P. The
      gills appeared less sensitive than the digestive gland to DNA lesions expressed
      as 8-oxodGuo and comet results. Good correlations were noted between 8-oxodGuo
      and comet. MDA and DNA damage did not correlate as well, although it was stronger
      in the digestive gland than in the gills. Production of mucus by the gills likely
      served to prevent lesions by reducing the bioavailability of the chemicals
      tested, which could explain that dose-effect relationships and synergistic
      effects were not observed.

PMID- 16097393
TI  - Scale of classification based on biochemical markers in mussels: application to
      pollution monitoring in Mediterranean coasts and temporal trends.
AB  - A battery of biochemical parameters was used to evaluate the response of mussels
      to a contaminated coastal environment. A multimarker approach was developed,
      establishing a scale for the classification of the water quality in European
      coastal sites (BIOMAR European programme). This study allows the evaluation of
      the temporal trends of this scale when applied to selected sites of European
      Mediterranean coast (BEEP Biological Effects of Environmental Pollution in Marine
      Coastal Ecosystems: European programme). Acetylcholinesterase activity (AChE) is
      highly sensitive to organophosphorus and carbamate insecticides and, to some
      extent, also to heavy metals. Catalase activity (CAT) and lipid oxidation
      (evaluated as malonedialdehyde) are markers of oxidative stress, glutathione S
      transferase (GST) activity is related to conjugation of organic compounds and
      benzo(a)pyrene hydroxylase activity (BPH) is a marker of effect of certain planar
      organic compounds (e.g. polycyclic aromatic hydrocarbons, PAHs). These parameters
      were measured either in gills (AChE, GST) or digestive gland (BPH, GST, CAT,
      MDA). For each biomarker, a discriminatory factor was calculated (maximum
      variation range/confidence interval) and a response index was allocated. For each
      site, a Multimarker Pollution Index (MPI) was calculated as the sum of the
      response index of each of the five more discriminating biomarkers. As the result
      of our calculation method, the quality of the coastal environment at each site
      can be classified according to a five levels scale. Samples collected for five
      cruises in May 2001, 2002, 2003, and September 2001 and 2002 showed MPI
      evolutions. The results show that water quality can be classified from class 1
      (clean areas in some sites of France, Italy and Spain) to class 4 (high pollution
      in main harbours). Results of the use of the biomarker scale in WP3 (Work Package
      Concernant Biomonitoring Programmes in Mediterranean Sea) during the BEEP
      programme make a strong contribution to the establishment of standardized
      strategies and methods for internationally agreed protocols for biomarker-based
      monitoring programmes. In comparison with scale pollution methodology used in the
      BIOMAR programme, the main contribution of BEEP was (1) to select from
      discriminatory analysis the biomarkers to be included in calculation of scale
      pollution; (2) to improve the use of the biomarker index in order to identify the
      main contaminants by analysis of individual contributions to the MPI; and (3) to
      apply methodology for temporal trends at sampled sites.

PMID- 16097394
TI  - Polymorphisms in glutathione S-transferases in French vinyl chloride workers.
AB  - The authors have recently demonstrated a significant gene-environment interaction
      between vinyl chloride exposure and polymorphisms in the DNA repair protein XRCC1
      on the occurrence of mutant p53 biomarkers of vinyl chloride-induced genetic
      damage. The aim of this study was to examine the polymorphisms in the glutathione
      S-transferases (GSTs) as potential modifiers of this relationship, since these
      enzymes may be involved in the phase II metabolism of the reactive intermediates
      of vinyl chloride. A cohort of 211 French vinyl chloride workers was genotyped
      for common polymorphisms in GSTM1, GSTT1 and GSTP1. Although no independent,
      statistically significant effect of these polymorphisms on the occurrence of the
      mutant p53 biomarker was found, the null GSTM1 and null GSTT1 polymorphisms were
      found to interact with the XRCC 1 polymorphism to increase the occurrence of the
      biomarker such that, for example, workers with at least one variant XRCC1 allele
      who were null for both GSTM1 and GSTT1 had a significant odds ratio for the
      biomarker (OR =8.4, 95% CI = 1.3 54.0) compared with workers who were wild-type
      for all alleles, controlling for potential confounders including cumulative vinyl
      chloride exposure.

PMID- 16097395
TI  - New and improved biomarkers ready to be used in health-risk oriented exposure and
      susceptibility assessments: report of the 6th International Symposium on
      Biological Monitoring in Occupational and Environmental Health.

PMID- 16097396
TI  - Recalibration methods to enhance information on prevalence rates from large
      mental health surveys.
AB  - Comparisons between self-report and clinical psychiatric measures have revealed
      considerable disagreement. It is unsafe to consider these measures as directly
      equivalent, so it would be valuable to have a reliable recalibration of one
      measure in terms of the other. We evaluated multiple imputation incorporating a
      Bayesian approach, and a fully Bayesian method, to recalibrate diagnoses from a
      self-report survey interview in terms of those from a clinical interview with
      data from a two-phase national household survey for a practical application, and
      artificial data for simulation studies. The most important factors in obtaining a
      precise and accurate 'clinical' prevalence estimate from self-report data were
      (a) good agreement between the two diagnostic measures and (b) a sufficiently
      large set of calibration data with diagnoses based on both kinds of interview
      from the same group of subjects. From the case study, calibration data on 612
      subjects were sufficient to yield estimates of the total prevalence of anxiety,
      depression or neurosis with a precision in the region of +/-2%. The limitations
      of the calibration method demonstrate the need to increase agreement between
      survey and reference measures by improving lay interviews and their diagnostic
      algorithms.

PMID- 16097397
TI  - Buprenorphine and methadone in the treatment of opioid dependence: methods and
      design of the COBRA study.
AB  - Buprenorphine and methadone are the two established substitution drugs licensed
      in many countries for the treatment of opioid dependence. Little is known,
      however, about how these two drugs are applied and how they work in clinical
      practice. In this paper we present the aims, methods, design and sampling issues
      of a collaborative multi-stage epidemiological study (COBRA) to address these
      issues. Based on a nationally representative sample of substitution physicians,
      the study is designed as an observational, naturalistic study, consisting of
      three major parts. The first part was a national survey of substitution doctors
      (prestudy, n = 379 doctors). The second part was a cross-sectional study (n = 223
      doctors), which consisted of a target-week assessment of 2,694 consecutive
      patients to determine (a) the severity and problem profiles and treatment
      targets; (b) the choice and dosage scheme of the substitution drug; (c) past and
      current interventions, including treatment of comorbid hepatitis C; and (d) cross
      sectional differences between the two drugs with regard to comorbidity, clinical
      course, acceptance/compliance and social integration. The third part consists of
      a prospective-longitudinal cohort study of 48 methadone-treated and 48
      buprenorphine-treated patients. The cohort is followed up over a period of 12
      months to investigate whether course and outcome of the patients differ by type
      or treatment received in terms of clinical, psychosocial, pharmaco-economic and
      other related measures. The response rate among substitution doctors was 57.1%;
      that among eligible patients was 71.7%. Comparisons with the federal registers
      reveal that the final samples of doctors and patients may be considered
      nationally representative with regard to regional distribution, training, type of
      setting as well as the frequency of patients treated with buprenorphine or
      methadone. The COBRA study provides a unique comprehensive database, informing
      about the natural allocation and intervention processes in routine care and about
      the course and outcome of patients treated with buprenorphine or methadone.

PMID- 16097398
TI  - Resilience in relation to personality and intelligence.
AB  - Resilience is a construct of increasing interest, but validated scales measuring
      resilience factors among adults are scarce. Here, a scale named the Resilience
      Scale for Adults (RSA) was crossvalidated and compared with measures of
      personality (Big Five/5PFs), cognitive abilities (Raven's Advanced Matrices,
      Vocabulary, Number series), and social intelligence (TSIS). All measures were
      given to 482 applicants for the military college. Confirmatory factor analyses
      confirmed the fit of the five-factor model, measuring 'personal strength',
      'social competence', 'structured style', 'family cohesion' and 'social
      resources'. Using Big Five to discriminate between well adjusted and more
      vulnerable personality profiles, all resilience factors were positively
      correlated with the well adjusted personality profile. RSA-personal strength was
      most associated with 5PFs-emotional stability, RSA-social competence with 5PFs
      extroversion and 5PFs-agreeableness, as well as TSIS-social skills, RSA
      structured style with 5PFs-conscientiousness. Unexpectedly but interestingly,
      measures of RSA-family cohesion and RSA-social resources were also related to
      personality. Furthermore, the RSA was unrelated to cognitive abilities. This
      study supported the convergent and discriminative validity of the scale, and thus
      the inference that individuals scoring high on this scale are psychologically
      healthier, better adjusted, and thus more resilient.

PMID- 16097399
TI  - The factor structure of the DSM-III-R personality disorders: an evaluation of
      competing models.
AB  - Confirmatory factor analysis was used to test a series of competing models to
      determine the best way to characterize the factor structure of the DSM-III-R
      personality disorder scores. Data were collected from 301 clients with a primary
      diagnosis of anxiety disorder. The Structured Clinical Interview for DSM-III-R
      (SCID) was used to determine Axis I and Axis II diagnoses, and adequate to good
      reliability was obtained for the number of criteria met for a given personality
      disorder. Several factor models were tested, including a single-factor model, a
      three-factor model based on the DSM grouping of odd, dramatic, and anxious
      personality disorders, and a four-factor model based on normal personality
      theories. Only the DSM three-factor model received strong and unequivocal
      support.

PMID- 16097401
TI  - A continuing success story.

PMID- 16097400
TI  - Generalizability of brief psychiatric rating scale prototypical profiles and
      their use in evaluating treatment outcomes.
AB  - The generalizability of previously isolated prototypical profiles of the Brief
      Psychiatric Rating Scale (BPRS) was examined in a sample of homeless individuals
      with both severe mental illness and substance-use problems who were part of a 24
      month study that evaluated the effectiveness of various treatment interventions.
      These prototypical profiles (depressed, actively psychotic, and withdrawn) did
      generalize to the new sample, with a 59.4% coverage rate. In addition, some of
      the participants' BPRS profiles (10%) were characterized by negative correlations
      with the withdrawn profile (termed agitated) and others (17%) by minimal within
      profile variability (labelled flat). Overall, with these additions, the coverage
      of the prototypical profiles was 86.4%. These prototypical profiles were then
      used to evaluate changes in profile elevation and shape over the course of the
      study. Generally, changes in both profile elevation and shape were moderated by
      the particular prototypical profile that the participants resembled. The use of
      these prototypical profiles in evaluating change permits a more precise analysis
      of what kind of individuals manifest particular effects. The clinical meaning of
      the BPRS profile changes observed was also discussed.

PMID- 16097402
TI  - Transcranial magnetic stimulation as a therapeutic tool in psychiatry.
AB  - Transcranial magnetic stimulation (TMS) is a patient-friendly stimulation
      technique of the brain with interesting perspectives. In clinical psychiatry,
      limited data are available on activity in psychosis and anxiety, but much
      research has been done in depression. Major concerns on published papers are the
      inconsistency of used parameter settings, the restraint numbers of patients in
      randomised trials, the lack of real sham controlled studies and the quasi
      inexistent reproducibility of results. The most stringent meta-analysis of TMS in
      affective disorders found a modest, statistically significant antidepressant
      effect after 2 weeks of daily treatment of high frequency repetitive left
      dorsolateral prefrontal cortex stimulation. Although most results are rather weak
      and not convincing enough to promote TMS as evidence-based antidepressive
      therapy, they show a measurable action that should not be ignored. Preclinical
      and clinical effects were observed analysing heterogeneous data, and results
      comparing TMS to electroconvulsive therapy (ECT) in affective disorders are
      encouraging. Efforts should continue with emphasis on increasing homogeneity and
      reproducibility in data. Further refinement of stimulation parameters should be
      established, so that new and large double-blind, long-term, sham-controlled
      trials can bring us to better understanding and standardising TMS procedure,
      finally leading to definitive conclusions about its efficacy in psychiatry.

PMID- 16097403
TI  - Antioxidative and steroid systems in neurological and psychiatric disorders.
AB  - A large number of neurological and psychiatric diseases like Morbus Parkinson,
      amyotrophic lateral sclerosis, dementia, schizophrenia and probably also
      affective disorders show an enhanced production of reactive oxygen species.
      Moreover, alterations of antioxidative systems and beneficial effects of
      antioxidative substances including steroid compounds such as estrogens have been
      described in several of these diseases. This review focuses on alterations of
      antioxidative systems in the course of neurological diseases and psychiatric
      disorders and on the differential effects of steroids on these systems in the
      central nervous system. Moreover, a possible clinical relevance of alterations of
      circulating steroids and of steroid treatment under these conditions is
      discussed.

PMID- 16097404
TI  - Frequency and characteristics of recurrent major depressed patients with
      unimpaired executive functions.
AB  - Major depression is associated with impairment of cognitive functions, and
      especially higher-order cognitive processes referred to as executive functions
      (EF). Whether this is a general finding is unclear. Patients without EF
      impairment may have different treatment needs than patients with EF impairment,
      and will probably have a better everyday functioning. Thus, it is important to
      identify the prevalence and characteristics of depressed patients without EF
      impairment. Forty-three patients with recurrent major depressive disorder (19-51
      years) and 50 healthy controls were included in the study. The subjects were
      assessed with neuropsychological tests selected to measure central areas of EF,
      and screened on clinical and demographic variables. Within the depressed group, a
      total of 56% were defined as EF unimpaired. These patients were characterised by
      higher intellectual abilities and fewer depression episodes than the subgroup of
      patients with EF impairment. The subgroups were similar in age at debut of
      illness, severity of depression, general psychopathology and global level of
      functioning. In conclusion, about half of patients with recurrent major
      depression have normal EF. Since cognitive impairment and depressive
      symptomatology seem to be distinct dimensions, a neuropsychological investigation
      could help to ensure optimal treatment in patients with recurrent major
      depression.

PMID- 16097405
TI  - Problems associated with the classification and diagnosis of psychiatric
      disorders.
AB  - Several methodological issues of classification of psychiatric disorders are
      addressed. Beside some historical aspects and basic characteristics of the
      classification of mental disorders, the advantages and disadvantages of the
      syndromatological and nosological classifications are broadly described. Finally
      the current situation of the international standardisation of psychiatric
      classification and particuarly the improvement of reliability by using
      operationalised procedures is discussed.

PMID- 16097406
TI  - Citalopram plus reboxetine in treatment-resistant obsessive-compulsive disorder.
AB  - While serotonin reuptake inhibitors (SRIs) are the first-line treatment of
      obsessive compulsive disorder (OCD), as many as 40-60% of patients fail to
      respond to adequate trials with these drugs. In this study, we describe the case
      of a patient with an SRI-resistant OCD who was successfully treated with a
      combination of citalopram (a selective SRI) and reboxetine (a selective
      noradrenaline reuptake inhibitor (SNRI)). This report suggests that future
      studies accessing the efficacy of the SRI SNRI combination in treatment resistant
      OCD are needed.

PMID- 16097407
TI  - A cath lab hero is something to be? Comments on left main stem percutaneous
      coronary intervention for ST-elevation myocardial infarction.

PMID- 16097408
TI  - Guidelines and registries: secondary prophylaxis after AMI with emphasis on the
      use of beta-blockers and ACE inhibitors.

PMID- 16097409
TI  - EC-coupling in normal and failing hearts.
AB  - Systolic heart failure may be due to too few cardiomyocytes, or to reduced
      contractile function of the heart cells. In the latter situation the myocardial
      function is impaired and this condition is called myocardial failure. The
      pathophysiological mechanism behind this cellular defect is not known, but Ca2+
      handling is altered. Although the most important trigger of sarcoplasmatic
      reticulum (SR) Ca2+ release, the L-type Ca2+ current, seems to be unaltered, SR
      Ca2+ load is reduced in human heart failure. This could explain the reduced
      contractility observed in failing hearts. Three possible mechanisms have been
      suggested to explain the reduction in SR Ca2+ load. They are leak through the SR
      Ca2+ release channel (RyR), impaired SR Ca2+ ATPase (SERCA) function and
      increased Na+/Ca2+-exchanger (NCX) function. Leak through RyR is not consistently
      found. Increased NCX function is probably secondary to a change in Ca2+ handling,
      and thus not a primary mechanism, but blockade of the NCX might have therapeutic
      potential. Reduced SERCA function is probably a primary mechanism for the
      observed systolic dysfunction, and further insight is to be gained through
      studies in genetically modified models.

PMID- 16097410
TI  - Percutaneous revascularization in acute myocardial infarction due to left main
      stem occlusion.
AB  - Following the encouraging results of trials testing the effect of primary
      percutaneous coronary intervention (PCI) more cases of left main arterial
      stenosis (LMS) as culprit lesions in acute myocardial infarction (AMI) are being
      handled. Not many cases of primary PCI on LMS have been published. We present 12
      cases of primary PCI on LMS. Eighty-three percent of the patients presented with
      cardiogenic shock and only 42% were discharged alive. Due to the high rate of
      cardiogenic shock at presentation, PCI seems to be the treatment of choice, over
      coronary artery bypass grafting (CABG), although one might consider using PCI as
      a bridge over to CABG.

PMID- 16097412
TI  - Sex differences in plaque morphology may explain the higher male prevalence of
      myocardial infarction compared to angina pectoris. The Tromso Study.
AB  - OBJECTIVES: To study whether the degree of carotid atherosclerosis and the male
      predominance of echolucent plaques could explain the sex difference in myocardial
      infarction (MI) compared to angina pectoris (AP). DESIGN: Ultrasound examination
      of the carotid artery was performed in 6727 persons. The presence of plaque,
      plaque thickness and number of segments with plaque were recorded. Plaque
      morphology in terms of echogenicity was scored as echolucent (soft plaque) or
      echogenic (hard plaque). A questionnaire was used to obtain information about
      coronary heart disease. RESULTS: In men with the most advanced atherosclerosis,
      the risk (OR, 95% CI) of having MI compared to those with no carotid
      atherosclerosis was less than half as the corresponding risk in women (2.2, 1.4
      3.3 vs 5.3, 2.6-10.6). For MI, the male-to-female ratio was highest in the group
      with no carotid plaque and declined by increasing burden of atherosclerosis. For
      AP, the sex ratio was independent of the degree of atherosclerosis. CONCLUSIONS:
      The findings support the hypothesis that the sex difference in MI compared to AP
      is due to the higher male prevalence of echolucent plaque.

PMID- 16097411
TI  - Target vessel revascularization following percutaneous coronary intervention. A
      10-year report from the Danish Percutaneous Transluminal Coronary Angioplasty
      Registry.
AB  - OBJECTIVE: To present the rate of target vessel revascularization (TVR) in a
      consecutive and unselected national population over 10 years. DESIGN: From 1989
      to 1998 all percutaneous coronary interventions (PCIs) performed in Denmark were
      recorded in the Danish PTCA Registry. RESULTS: From 1989 to 1998 the annual rate
      of PCI rose from 46 to 753 per million inhabitants. From 1995 to 1998 TVR with
      PCI or coronary artery bypass grafting (CABG) within 9 months from the index PCI
      decreased significantly (p < 0.001) from 21.2% in 1995 (CABG 8.6% vs PCI 12.6%)
      to 11.7% in 1998 (CABG 4.3% vs PCI 7.4%). Independent predictors for TVR were:
      coronary stenting (OR 0.60; 95% CI 0.52-0.69, p < 0.001), primary success rate
      (OR 0.69; 95% CI 0.53-0.89, p < 0.005), pre-PCI stenosis severity (OR 1.01; 95%
      CI 1.00-1.01, p = 0.03), left anterior descending coronary artery (OR 2.35; 95%
      CI 1.73-3.19, p < 0.001), right coronary artery (OR 1.61; 95% CI 1.17-2.20, p =
      0.003), sapheneous vein graft (OR 2.03; 95% CI 1.13-3.63, p = 0.017) and age (OR
      0.99; 95% CI 0.98-1.00, p = 0.002). CONCLUSION: Coronary stenting, primary
      success rate, pre-PCI stenosis severity, age and treated vessel were independent
      predictors for TVR.

PMID- 16097413
TI  - Nationwide trends in the prescription of beta-blockers and angiotensin-converting
      enzyme inhibitors after myocardial infarction in Denmark, 1995-2002.
AB  - OBJECTIVES: To study the use of beta-blockers and angiotensin-converting enzyme
      (ACE) inhibitors after acute myocardial infarction (AMI) in Denmark from 1995 to
      2002. DESIGN: Information about patients with first AMI aged > or = 30 years and
      the dispensing of beta-blockers and ACE inhibitors from pharmacies within 30 d
      from discharge was obtained from the National Patient Registry and the Danish
      Registry of Medicinal Product Statistics. RESULTS: Beta-blocker use increased
      from 38.1% of patients in 1995 to 67.9% in 2002 (OR = 3.85, CI: 3.58-4.13).
      Women, elderly patients and patients taking loop-diuretics and antidiabetic drugs
      received beta-blockers less frequently, but patients taking loop-diuretics or
      antidiabetic drugs had the greatest increase. ACE inhibitor use increased from
      24.5 to 35.5% (OR = 1.86, CI: 1.72-2.01). Women, patients aged < 60 years or > or
      = 80 years and patients not taking loop-diuretics received ACE inhibitors less
      frequently, but patients not taking loop-diuretics had the greatest increase.
      CONCLUSIONS: Beta-blocker use increased markedly post-AMI from 1995 to 2002,
      whereas ACE inhibitor use increased modestly. The results suggested
      undertreatment of women, elderly patients and people with diabetes.

PMID- 16097415
TI  - Suppressed phospholamban levels differentiate irreversibly dysfunctional from
      hibernating myocardium in humans.
AB  - OBJECTIVES: We studied whether dysfunction of human hibernating (HIB) and
      irreversibly dysfunctional myocardium (IRDM) are associated with altered levels
      of the sarcoplasmatic reticulum calcium handling proteins Ca2+-ATPase (SERCA2a)
      and its inhibitor phospholamban (PLB). DESIGN: In 12 patients myocardial biopsies
      were taken during bypass surgery and analysed for contents of these proteins. We
      classified regions as control, HIB, or IRDM based on echocardiographic studies
      before and 6 months after surgery. RESULTS: SERCA2a content (mean+/-SEM) was
      similar to control in HIB and IRDM (2.6 +/- 1.7, 3.8 +/- 2.0, and 3.4 +/- 1.9
      units/g non-collagen protein (NCP), p = 0.40). PLB content was similar to control
      in HIB (2.6 +/- 0.4 and 3.5 +/- 0.5 units/microg NCP) but reduced in IRDM (0.9 +/
      0.2 units/microg NCP, p < 0.05). SERCA2a:PLB ratio, an indicator of SERCA2a
      activity, did not differ between control and HIB (1.2 +/- 0.3 and 1.4 +/- 0.4
      units/microg NCP) but was increased in IRDM (5.1 +/- 1.7 units/microg NCP, p <
      0.05). CONCLUSIONS: Inappropriate SERCA2a activity due to suppressed PLB levels
      may represent a maladaptive mechanism in chronic ischemic myocardium being
      causally linked to irreversibility of left ventricular dysfunction.

PMID- 16097414
TI  - Patients with ischemic heart disease: quality of life predicts long-term
      mortality.
AB  - OBJECTIVE: We have investigated whether perceived quality of life has an impact
      on long-term survival after a cardiac event. DESIGN: Male (n = 316) and female (n
      = 97) patients were assessed by means of a self-administered quality of life
      questionnaire 1 year after either acute myocardial infarction (n = 296), coronary
      artery bypass grafting surgery (n = 99) or percutaneous coronary intervention (n
      = 18). Inclusion period was 1989-1991. Ten years after the last patient answered
      the 1-year questionnaire, mortality (status factor) up to census date was
      analysed using nine dimensions of quality of life as covariates (Cox regression).
      RESULTS: At 1-year assessment, subjective general health (RR = 3.15), perceived
      arrhythmia (RR = 1.72), experience of sex life (RR = 1.55), perceived
      breathlessness (RR = 1.50) and experience of self-esteem (RR = 1.48) were all
      significantly related to death within the period up to census date. CONCLUSION:
      The findings highlight that the patients' own experience of his or her quality of
      life, has a prognostic importance for long-term mortality after a cardiac event.
      Clinicians should be aware that a careful monitoring of perceived quality of life
      is an important part of good patient care.

PMID- 16097416
TI  - Reduced release of vasoconstrictors from the porcine heart after repeated periods
      of ischemia.
AB  - OBJECTIVE: To examine if the decline in post-ischemic hyperemic flow after
      repeated brief periods of myocardial ischemia is accompanied by augmented cardiac
      release of the vasoconstrictors endothelin-1 (ET-1) and norepinephrine (NE).
      DESIGN: Mid-LAD (left anterior descending coronary artery) was occluded for 10
      min with 30 min intervals a total of four times in six anesthetized pigs. Blood
      from the anterior interventricular coronary vein was drained through a shunt to
      the right atrium to facilitate blood sampling. Plasma concentrations of ET-1 and
      NE were repeatedly measured in arterial and coronary venous blood to estimate
      cardiac vasoconstrictor release. RESULTS: Plasma concentrations of ET-1 and NE
      remained unaltered, but cardiac release of both vasoconstrictors rose briefly
      during reperfusion due to the hyperemia. However, release declined progressively
      after repeated periods of ischemia and reperfusion and amounted to 53% (NE) and
      17% (ET-1) of initial release after the fourth period of ischemia. CONCLUSION:
      The decline in post-ischemic hyperemia after repeated brief periods of myocardial
      ischemia is not accompanied by a progressive accentuation of cardiac ET-1 and NE
      release.

PMID- 16097417
TI  - Assessment of validity for EuroSCORE risk stratification system.
AB  - Prognostic scoring helps doctors, patients and their families to weigh the risks
      and benefits of medical care and clarifies their expectations. OBJECTIVE: We
      aimed to analyze the risk stratification performance of the EuroSCORE system
      because of its common use in Lithuania. DESIGN: EuroSCORE performance is assessed
      in terms of sensitivity, specificity, accuracy and area under the receiver
      operating characteristic (ROC) curve (AUC). Logistic regression is carried out
      for modeling categorical data and odds ratio calculations of being a non-survivor
      case for each EuroSCORE risk group. RESULTS: The study was completed on 1002
      patients. Mean score for EuroSCORE was 4.77 +/- 2.8; ROC curve of 0.71; accuracy
      was 65.5%; 65.4% sensitivity and 67.2% specificity. CONCLUSIONS: EuroSCORE
      created a moderately predictive area under the ROC curve for our patient
      population. Probability of non-survival by logistic regression model for each
      EuroSCORE risk group is statistically significantly higher compared to the lower
      risk group. Predictions available from prognostic scoring systems could be useful
      in decision making when there is uncertainty in whether to carry out surgery or
      not.

PMID- 16097418
TI  - Predictors of postoperative mortality after mitral valve repair: analysis of a
      series of 164 patients.
AB  - BACKGROUND: Mitral valve repair (MVR) has been shown to achieve good long-term
      results. However, this procedure is associated with relevant immediate
      postoperative mortality. The aim of this study is to identify those preoperative
      variables associated with an increased risk of 30-d postoperative death. METHODS:
      One hundred and sixty-four patients underwent MVR at our institution from January
      1993 to December 2000. RESULTS: Eleven patients (6.7%) died during the immediate
      postoperative outcome, a median of 14 d after surgery (range, 1-29 d). One
      patient (1.3%) out of 80 who underwent MVR as lone procedure died on
      postoperative day 14 of cardiac tamponade. The mortality rate in those who
      underwent MVR associated with other procedures was 11.9%. Multivariable analysis
      (154 patients included in the analysis) showed that patients' age (p = 0.006, for
      an increase of 10 units: OR 4.33, 95% CI 1.53-12.27), history of prior cardiac
      surgery (p = 0.006, OR 118.56, 95% CI 4.03-3491.14) and NYHA functional class (p
      = 0.011, OR 5.66, 95% CI 1.49-21.49) were significantly associated with an
      increased risk of postoperative death. The receiver operating characteristics
      (ROC) curve showed that patients' age had an area under the curve of 0.762 (95%
      CI 0.622-0.901, p = 0.004), its best cut-off value being 65 years (mortality,
      13.4% vs 2.1%, p = 0.008, sensitivity 81.8%, specificity 62.1%, accuracy 63.4%).
      None of the patients older than 65 and with a history of prior cardiac surgery
      survived the operation. CONCLUSIONS: MVR is associated with a relevant 30-d
      mortality risk in patients older than 65 years, with advanced NYHA functional
      class and a history of prior cardiac surgery.

PMID- 16097419
TI  - Peripheral blood monocyte activation during coronary artery bypass grafting with
      or without cardiopulmonary bypass.
AB  - OBJECTIVE: The aim of this prospective, randomized study was to investigate the
      impact of coronary artery bypass grafting (CABG) on peripheral monocytes and to
      evaluate the additional effect of cardiopulmonary bypass (CPB). DESIGN: Twenty
      patients admitted for elective CABG were randomized to either on-pump (ONCAB, n =
      9) or off-pump (OFFCAB, n = 11) surgery and blood samples were drawn before,
      during and 24 h after the operation. The total number of monocytes and the
      proportion of the more mature CD16+/CD14+ monocytes were measured. Expression of
      activation markers (CD11b, CD35 and CD62L) and oxidative burst were determined
      using flow cytometry on both resting and in vitro stimulated cells. Serum
      concentrations of soluble CD14 and monocytes/macrophage chemotactic protein 1
      (MCP-1) were analysed. RESULTS: During surgery there was a selective decrease in
      the proportion of CD16+/CD14+ monocytes compared to total monocytes. These had
      returned to preoperative values 24 h after surgery while the total number of
      monocytes had increased more than 100%. Intracellular production of oxygen free
      radical H2O2 was increased in the ONCAB group during surgery compared to OFFCAB.
      Monocyte expression and in vitro mobilization of complement receptors, CD11b and
      CD35, were similar in both study groups during and after surgery as was the
      expression of CD62L. Serum levels of MCP-1 decreased during surgery as did
      soluble CD14, both with increased levels again the day after surgery. CONCLUSION:
      It is concluded that the circulating monocyte population is activated during and
      as a consequence of CABG. There were few apparent additional effects of CPB found
      in this study. In this setting the inflammation caused by the surgery procedure
      per se probably surpasses the impact of the CPB on circulating blood monocytes.

PMID- 16097420
TI  - Antegrade selective cerebral perfusion with mild hypothermic systemic circulatory
      arrest during thoracic aortic surgery.
AB  - OBJECTIVE: Antegrade selective cerebral perfusion (ASCP) and retrograde cerebral
      perfusion (RCP) have proven to be reliable methods of brain protection during
      aortic surgery. These techniques are usually accompanied by systemic circulatory
      arrest with moderate hypothermia (24-28 degrees C) or deep hypothermia (18-24
      degrees C). However, hypothermia can lead to various problems. The present study
      therefore reports results for thoracic aorta replacement using ASCP with mild
      hypothermic systemic arrest (28-32 degrees C). DESIGN: Between 1995 and 2003, 68
      consecutive patients underwent repair of the ascending aorta and/or aortic arch.
      Mild hypothermic ASCP was utilized in 31 cases, moderate hypothermic ASCP in 20,
      and deep hypothermic RCP in 17. Various parameters were compared between the mild
      hypothermic ASCP, moderate hypothermic ASCP, and RCP. RESULTS: Hospital mortality
      was 10.3%, with no significant differences observed between any groups. Permanent
      neurological dysfunction was 8.8%, and no significant differences were observed
      between any groups. Mild hypothermic ASCP displayed significantly decreased
      transfusion volume, intubation time, and ICU stay. CONCLUSIONS: Use of ASCP with
      mild hypothermic systemic circulatory arrest during aortic surgery resulted in
      acceptable hospital mortality and neurological outcomes. ASCP with mild
      hypothermic arrest allows decreased transfusion volume and reduced duration of
      intubation and ICU stay.

PMID- 16097421
TI  - Outcome after emergency repair of symptomatic, unruptured abdominal aortic
      aneurysm: results in 42 patients and review of the literature.
AB  - OBJECTIVE: To evaluate the results of our experience in the management of
      patients with symptomatic, unruptured abdominal aortic aneurysm (AAA), to
      identify the predictors of immediate outcome and to define the worldwide
      postoperative mortality rate through a review of previous studies on this
      condition. PATIENTS AND METHODS: Forty-two patients underwent emergency repair
      for symptomatic, unruptured AAA. RESULTS: Four patients (9.5%) died during the in
      hospital stay, three of myocardial infarction and one of multiorgan failure. Only
      preoperative creatinine was predictive of postoperative death (p = 0.04, OR
      1.31). The Glasgow Aneurysm Score tended to be predictive of postoperative death
      (p = 0.06), survivors having had a median score of 76.0 (IQR, 75.5-82.1) and
      patients who died of 87.1 (78.9-89.9). The receiver operating characteristic
      (ROC) curve analysis showed that the Glasgow Aneurysm Score had an area under the
      curve of 0.789 (95% CI: 0.596-0.983, SE: 0.099, p = 0.06). Its best cut-off value
      in predicting postoperative death was 85 (specificity 86.8%, sensitivity 75.0%).
      The postoperative mortality rate among patients with a Glasgow Aneurysm Score <85
      was 2.9%, whereas it was 37.5% among those with a score >85 (p = 0.003). A review
      of the results of previous studies on this condition, including also the present
      series, showed that 207 out of 1312 patients (15.8%) died after emergency
      operation for symptomatic, unruptured AAA. CONCLUSION: Emergency open repair of
      symptomatic, unruptured AAA is associated with a high risk of postoperative
      death. The results of this study suggest that a rather good postoperative
      survival rate can be expected in patients with a Glasgow Aneurysm Score <85. A
      watchful waiting policy or, alternatively, emergency endovascular repair should
      be advocated in patients with a higher score.

PMID- 16097422
TI  - Predictor of neurologic dysfunction after elective thoracic aorta repair using
      selective cerebral perfusion.
AB  - OBJECTIVES: This study was undertaken to determine the factors that influence
      postoperative neurological dysfunction after selective cerebral perfusion (SCP).
      DESIGN: From 1995 to August 2004, 60 patients were evaluated for the presence of
      cerebro-vascular disease (CVD), and then underwent thoracic aortic operations
      using SCP. Perioperative factors were evaluated by multivariate analyses.
      RESULTS: Hospital mortality rate was zero. Sixteen patients (26.7%) proved to
      have CVD. Permanent neurological dysfunction (PND) appeared in three patients
      (5.0%) and transient neurological dysfunction (TND) in two (3.3%). Univariate
      analysis revealed superficial temporal artery (STA) pressure during SCP (p =
      0.0410) to be a significant risk factor for PND. Variables that achieved values
      of p < 0.2 (aortic cross-clamp time, presence of CVD, old cerebral infarction,
      presence of clots or atheroma) were examined with multivariate analysis and the
      presence of CVD (p = 0.038) and STA pressure during SCP (p = 0.032) were
      independent risk factors for PND. Multivariate analysis for TND did not show any
      risk factor. CONCLUSIONS: The presence of CVD was indicated as an independent
      risk factor for PND after thoracic aortic operations using SCP.

PMID- 16097423
TI  - Repair of complex left ventricular outflow tract obstruction in children.
AB  - BACKGROUND: Complex obstruction of the left ventricular outflow tract (LVOTO) in
      children may be treated with surgical procedures like the Ross-Konno or Koncz
      Konno procedures, or modifications thereof. We present our results from the last
      10 years. MATERIAL AND METHOD: During the period from December 1991 to April
      2002, 17 patients/children with complex LVOTO were operated on. Patients treated
      with balloon valvuloplasty, open commisurotomy or simple valve replacement are
      excluded. The procedures performed were: Koncz-Konno (KK) or modified KK (n =
      10), Ross-Konno (RK) (n = 2) and Ross (RO) (n = 5). Concomitant procedures
      included mitral valve replacement (n = 1), aortic arc plasty (n = 1), subvalvular
      myotomi (n = 1), resection of subvalvular membrane (n = 1) and aorto-coronary
      bypass (n = 1). Patients' ages ranged from 1 to 178 months, median 71 months.
      Body weights ranged from 3.8 to 50.0 kg, median 19.4 kg. Eight cases were redo
      procedures. RESULTS: Three early deaths occurred. One patient in the KK group,
      one in the modified KK group and one in the RK group. One patient died 8 years
      postoperatively of unknown reasons; no autopsy was performed. The rest of our
      patients who survived the initial major surgical treatment show normal physical
      performance and their quality of life seems to be good. CONCLUSION: Patients with
      complex LVOTO can be operated with biventricular repair in selected cases. Early
      and late mortality are acceptable.

PMID- 16097424
TI  - Mechanical restitution curves reflect post-ischemic stunning in pigs.
AB  - OBJECTIVES: The time constant of mechanical restitution (T(MRC)), proposed to
      reflect changes in calcium release and uptake, has been shown to increase in left
      ventricular (LV) failure. In this study, we tested the hypothesis that T(MRC)
      also can identify post-ischemic, reversible LV dysfunction (stunning). DESIGN:
      Stunning was induced by a series of left main coronary artery occlusions in eight
      anesthetized open chest pigs. Left ventricular pressure-volume relations were
      assessed using a pressure-volume catheter during right atrial pacing. Mechanical
      restitution curves (MRCs) were constructed using two different measures of
      contractile response: maximal first derivative of pressure (CR(dP/dtmax)) and
      stroke work (CR(SW)). RESULTS: Mean arterial pressure, stroke volume and dP/dtmax
      were decreased 30 min after stunning. Slopes of end-systolic pressure volume
      relation and preload recruitable stroke work, however, showed no significant
      changes after stunning. For MRCs based on CR(dP/dtmax), T(MRC) increased in all
      eight animals. Using CR(SW), T(MRC) increased in seven out of eight pigs.
      CONCLUSIONS: Ischemia-reperfusion induce changes in MRCs based on CR(dP/dtmax),
      and CR(SW). The MRC concept may have potential as a clinical left ventricular
      performance index.

PMID- 16097425
TI  - Lack of cardioprotection from metabolic support with glutamine or glutamate in a
      porcine coronary occlusion model.
AB  - OBJECTIVE: Previous experimental studies indicate that glutamine or glutamate may
      provide cardioprotection by improving the oxidative metabolism in myocardial
      ischemia. We investigated the effect of glutamine or glutamate, given during
      reperfusion, on resulting infarct size and hemodynamic recovery. DESIGN: A
      porcine coronary occlusion model was applied. Infusions were initiated 15 min
      before reperfusion and supplemented with intracoronary bolus doses at
      reperfusion. The primary outcome measure was infarct size in relation to area at
      risk determined by a standard tissue staining procedure. Secondary outcome
      measures were the hemodynamic variables. RESULTS: The infarct sizes as a
      proportion of the area at risk (mean+/-SD) were: control group, 0.64 +/- 0.19 (n
      = 9); glutamine group, 0.87 +/- 0.07 (p < 0.05 vs control group) (n = 8);
      glutamate group, 0.72 +/- 0.11 (n = 9). Glutamine increased systemic vascular
      resistance, while glutamate preserved cardiac output during infusion. CONCLUSION:
      Substrate supplementation with the anaplerotic precursors glutamine and glutamate
      is ineffective as adjunctive therapy for severe myocardial ischemia. Beneficial
      effects documented in less complex experimental systems could not be transferred
      to a more pathophysiological relevant model.

PMID- 16097426
TI  - Children's hospitals prevent post-surgical infections.

PMID- 16097427
TI  - Poster helps to lower elevated blood glucose levels.
AB  - Educating clinicians about when elevated blood glucose levels should be
      controlled, along with implementing standardized insulin protocols and post
      operative orders, has greatly improved the treatment of patients with diabetes at
      Torrance Memorial Medical Center.

PMID- 16097428
TI  - Pittsburgh hospital increases OR utilization by 60%.
AB  - By setting some stricter ground rules for scheduling surgical cases, St. Clair
      Hospital in Pittsburgh, PA has been able to increase the utilization rate of its
      11 operating rooms from 45% to 72%.

PMID- 16097429
TI  - Heart specialists incorporate performance improvement measures into EMR.
AB  - Midwest Heart Specialists, a physician-owned cardiovascular practice with 55
      specialists serving the Chicago area, saved millions of dollars in 2004 on
      hospitalization costs for patients with coronary artery disease by integrating
      performance data collection into its existing electronic medical records system.

PMID- 16097430
TI  - Successful surgical benchmarking program moves to private sector.
AB  - In the late 1980s, Congress passed a law requiring all Veterans' Administration
      hospitals to report surgical outcomes annually on a risk-adjusted basis and
      compare them to national averages in the private sector. However, those national
      averages did not exist. Fifteen years later, efforts to remedy that oversight
      have led to the creation of the National Surgical Quality Improvement Program and
      dramatic successes in both patient care and cost management.

PMID- 16097431
TI  - Hospitalists take on role in rapid response teams with early success.
AB  - When the Institute for Healthcare Improvement came out with its campaign to save
      100,000 lives last December, one of the most prominent of the six suggestions
      made was for hospitals to form rapid response teams that would be available to
      check on at-risk patients before they became critically and irreversibly ill.

PMID- 16097432
TI  - High plasma corticosterone levels persist during frequent automatic blood
      sampling in rats.
AB  - Corticosterone levels in blood may be used as a marker of stress in rodents,
      provided that the blood sampling procedure itself is non-stressful. Automated
      blood sampling equipment (Accusampler) allows blood sampling without any
      interference with the animal and might be useful as a tool for an on-line
      measurement of stress markers in blood. However, the impact of the blood sampling
      itself on the corticosterone levels in blood is unknown. The present study was
      designed to evaluate whether the frequency of blood sampling influences the
      plasma corticosterone levels in male and female rats. During anaesthesia, a
      catheter was placed in the jugular vein and attached to an Accusampler. Blood
      samples (200 microl) were withdrawn with a high (24 samples) or low frequency (3
      samples) during a six-hour period immediately after the catheter insertion. The
      corticosterone levels in the plasma were quantified with ELISA. The
      corticosterone levels persisted at high post-operation concentrations when blood
      was collected frequently, while the levels steadily declined significantly during
      low-frequency sampling. The corticosterone levels were higher in female than in
      male rats, but the curves were similar. The present study elucidates the
      importance of considering the frequency of blood withdrawal during automated
      blood sampling. This parameter may have an impact on the experimental results
      when using blood corticosterone levels as a stress marker, but also during any in
      vivo study where blood is collected, since high corticosterone levels may affect
      the normal physiology of the animals.

PMID- 16097433
TI  - Establishment of an in vitro model using NR8383 cells and Mycobacterium bovis
      Calmette-Guerin that mimics a chronic infection of Mycobacterium tuberculosis.
AB  - BACKGROUND: Mycobacterium tuberculosis infection affects one-third of the world's
      population and causes the death of three million people each year. To clarify
      details of M. tuberculosis survival strategies, it is important to establish a
      suitable in vitro model that mimics a chronic infection in alveolar macrophages
      by M. tuberculosis. For this reason, we established a new in vitro model using a
      rat alveolar macrophage cell line, NR8383. MATERIALS AND METHODS: Basic
      characteristics, including phagocytotic ability and production of nitrogen oxide
      and tumor necrosis factor in response to several stimuli, of NR8383 cells were
      compared with those of primary alveolar macrophages. The course after
      phagocytosis of live or killed M. bovis bacilli Calmette-Guerin (BCG) was
      examined over 21 days using NR8383 cells as the host. RESULTS: The
      characteristics that have been examined to date were nearly the same for both
      primary alveolar macrophage and NR8383 cells. Live BCG phagocytosed by NR8383
      cells had successfully begun to grow in the cells within 7 days, while killed BCG
      were almost completely destroyed by 21 days. CONCLUSION: BCG-infected NR8383
      cells are potentially a suitable in vitro model that mimics a chronic infection
      with M tuberculosis.

PMID- 16097434
TI  - In vitro osteogenic differentiation is affected in Wiedemann-Rautenstrauch
      Syndrome (WRS).
AB  - BACKGROUND: Wiedemann-Rautenstrauch (neonatal progeroid) syndrome (WRS) is a rare
      autosomal recessive condition, with the characteristic appearance of premature
      aging already present at birth and other typical features (hypotrichosis,
      macrocephaly, mental retardation, aged face, generalized lipoatrophy, abnormal
      tooth status, osteopenia and other skeletal abnormalities). To date, there are no
      data about the differentiation capacity of WRS progenitor cells available in the
      literature. PATIENTS AND METHODS: To elucidate the osteoblastic and
      chondroblastic regeneration potential in WRS, a progenitor cell culture system
      was used. Bone marrow-derived stem cells of a 16-year-old WRS patient were
      cultivated and stimulated by dexamethasone, ascorbic acid and beta
      glycerolphosphate (DAG) over 21 days. Immunocytochemical stainings of CD34, CD45,
      CD105, osteocalcin, osteopontin and collagen II served for a quantitative
      evaluation of the differentiated cells. The results were compared to bone marrow
      derived stem cells of a healthy female volunteer donor. RESULTS: It was shown,
      for the first time, that WRS cells showed a highly significant lower in vitro
      response to osteoblastic differentiation stimulus. Furthermore, significantly
      fewer chondrocytes and hematopoietic cells were induced in WRS progenitors
      compared to the control group. CONCLUSION: Our data suggest a lack of cellular
      differentiation capacity in WRS patients, which may be responsible for the
      clinical appearance and symptoms of this rare disorder.

PMID- 16097435
TI  - Topoisomerase II alpha expression in breast ductal invasive carcinomas and
      correlation with clinicopathological variables.
AB  - Topoisomerase II alpha (topo IIa) is an enzyme that in normal cells is expressed
      predominantly in the S/G2/M-phase of the cell cycle. In malignant cells, in vitro
      studies have indicated that the expression of topo II alpha is both higher and
      less dependent on the proliferation state in the cell. To study the expression of
      topo IIa and the relationship between that expression-and other variables in
      cases of breast ductal invasive carcinomas, 50 fine-needle aspiration biopsies
      were performed from the same number of female patients, diagnosed cytologically
      and confirmed histologically after surgery. The same cases were studied
      immunocytochemically using monoclonal antibodies to topo IIa and Her2/neu (CB11)
      by the alkaline phosphatase method (APAAP). Topo IIa was found in 32 cases (64%)
      of the carcinomas studied. An overexpression between topo IIa and Her2/neu was
      found (p < 0.005). A relationship between topo IIa expression, histological grade
      and lymph node status (LNs) was also found (p < 0.005). Increased topo IIa
      expression seems to be related to an aggressive form of breast cancer featuring
      Her2 amplification and lymph node metastasis.

PMID- 16097436
TI  - The effect of hepatic stimulator substance (HSS) on liver regeneration arrest
      induced by 5-HT2 receptor blockade.
AB  - BACKGROUND: The restorative effect of hepatic stimulator substance (HSS) against
      hepatic regeneration arrest induced by 5-HT2 receptor blockade was investigated.
      MATERIALS AND METHODS: Male Wistar rats were subjected to 60-70% partial
      hepatectomy and to 5-HT2 receptor blockade at 16 h after partial hepatectomy by
      ketanserin administration (6 mg/kg bodyweight intraperitoneally; group I). HSS at
      the dose of 100 mg protein/kg bodyweight was administered at 10 or 17 h after
      partial hepatectomy in ketanserin-treated rats (groups II and III). The mitotic
      index in hematoxylin-eosin-stained liver sections, immunochemical detection of
      PCNA and Ki 67 nuclear antigens and the rate of [3H]-thymidine incorporation into
      hepatic DNA were used as indices of liver regeneration. RESULTS: Liver
      regeneration, as evaluated by [3H]-thymidine incorporation into hepatic DNA,
      mitotic index, PCNA and Ki67 nuclear antigens, peaked at 40 h in groups I, II and
      III of rats and no significant differences were observed between the studied
      groups. CONCLUSION: HSS administration is not capable of reversing the liver
      regeneration arrest induced by 5-HT2 receptor blockade.

PMID- 16097437
TI  - Ferulic acid dimer inhibits lipopolysaccharide-stimulated cyclooxygenase-2
      expression in macrophages.
AB  - Phenylpropanoids may act as nonsteroidal anti-inflammatory drug (NSAID)-like
      compounds. 4-cis, 8-cis-Bis (4-hydroxy-3-methoxyphenyl)-3, 7-dioxabicyclo
      [3.3.0]octane-2,6-dione (bis-FA, compound 2), a dimer of ferulic acid, was
      synthesized from ferulic acid (1), and its effect on lipopolysaccharide (LPS)
      stimulated cyclooxygenase-2 (COX-2) expression in RAW 264.7 cells was compared
      with those of the parent ferulic acid (1) and of iso-ferulic acid (3-hydroxy-4
      methoxycinnamic acid) (3). LPS-induced gene expression of COX-2 was markedly
      inhibited by compound 2 at a concentration of 10 microM and by compound 3 at 100
      microM, but was not inhibited by compound 1 at 100 microM. This observation
      suggests that compound 2 may possess potent anti-inflammatory activity. These
      ferulic acid-related compounds were able to scavenge the stable 1, 1-diphenyl-2
      picrylhydrazyl (DPPH) radical. The 50% inhibitory concentration for DPPH radicals
      declined in the order 3 (40.20 mM) > 2 (3.16 mM) > 1 (0.145 mM). Compound 1
      possessed potent anti-radical activity, but no COX-2 inhibitory activity, which
      may be a result of enhancement of its conjugate properties by abstraction of an H
      atom from the phenolic OH group, causing loss of phenolic function. In contrast,
      inhibition of COX-2 expression by compounds 2 and 3 could be caused by their
      increased phenolic function, which is associated with decreased anti-radical
      activity. Compounds 2 and 3, particularly 2, may have potential as NSAID-like
      compounds.

PMID- 16097438
TI  - Elevated plasma levels of bilirubin in patients with neurotrauma reflect its
      pathophysiological role in free radical scavenging.
AB  - Bilirubin, a powerful endogenous antioxidant, is one of the catabolites of heme
      oxygenases (HOs). In this study, the plasma bilirubin concentration was measured
      to establish bilirubin kinesis after traumatic brain injury (TBI). Furthermore,
      in in vitro studies, the free radical scavenging activity and antioxidant potency
      of bilirubin was also investigated at various concentrations, including
      physiological ones. Indirect plasma bilirubin was measured in 25 patients on days
      1, 2, 3 and 4 after presentation with TBI. The ability of bilirubin to scavenge
      the hydroxyl (OH) and 1,1-diphenyl-2-picrylhyrazyl (DPPH) radicals, and its
      antioxidant potency, were also analyzed using electron spin resonance (ESR) and
      the bioantioxidant power (BAP) methods, respectively. Plasma bilirubin levels
      were significantly higher on days 2, 3 and 4 than on patient admission (day 1; p
      < 0.05). ESR and BAP results revealed that bilirubin has direct OH and DPPH
      radical scavenging activities and potent antioxidant effects in vitro at
      physiological concentrations. These data indicate that physiological
      concentrations of bilirubin have antioxidant properties and that it constitutes
      one of the biological defense mechanisms in neurotrauma patients.

PMID- 16097439
TI  - Combination of oral fluoropyrimidine and docetaxel: reappraisal of synergistic
      effect against gastric carcinoma xenografts.
AB  - BACKGROUND: The synergistic antitumor effect of a combination of docetaxel and
      capecitabine is reported to be attributable to docetaxel-mediated up-regulation
      of thymidine phosphorylase (dThdPase). MATERIALS AND METHODS: Intravenous
      docetaxel (15 mg/kg) was given to nude mice bearing xenografts of the gastric
      cancer cell lines MKN45 and MKN28. Mice were sacrificed on days 7, 10 and 22 and
      tumor samples were taken to measure the activities of thymidylate synthase,
      dihydropyrimidine dehydrogenase, dThdPase and orotate phosphoribosyltransferase.
      The efficacy of capecitabine or S-1, alone and in combination with docetaxel, was
      then evaluated in vivo. Docetaxel was administered intravenously on days 8 and 22
      at 15 mg/kg, while capecitabine (269 mg/kg) or S-1 (7.5 mg/kg) were administered
      orally 5 times a week for 4 weeks. RESULTS: Tumor regression was observed only
      for a combination of capecitabine and docetaxel against MKN28, while additive
      growth inhibition was obtained by the combination of docetaxel and both S-1 and
      capecitabine on MKN45 tumor xenografts. Induction of dThdPase activity was
      observed only for MKN45. The activity of no other enzyme was significantly
      affected following administration of docetaxel. CONCLUSION: The combination of
      oral fluoropyrimidine and docetaxel showed augmented antitumor activity, but this
      may be attributed to mechanisms other than changes in 5-fluorouracil-metabolizing
      enzymes.

PMID- 16097440
TI  - Lack of prevention of large intestinal cancer by VPS, an extract of Coriolus
      versicolor mushroom.
AB  - Cancer prevention studies were conducted with VPS, a hot water extract of the
      Coriolus versicolor (CV) mushroom, in female Swiss mice. The extract was
      administered in the diet for life to the animals. Three groups of mice received
      the following treatments: a). 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was
      administered as 10 weekly subcutaneous injections of 20 microg/g body weight,
      starting at 9 weeks of age; b). VPS was given at a 2% dose level starting at 7
      weeks of age followed by 1,2-DMH, as described in group a; c). 1,2-DMH was
      administered as described in group a followed by VPS at a 2% dose level starting
      at 21 weeks of age. The number of animals with large intestinal tumors and the
      total number of these tumors were: a). 30,321; b). 29,359; and c). 28,415. These
      differences are not statistically significant. Because extracts of the CV
      mushroom are used by cancer patients as nutritional supplements in the U.S., and
      particularly in the Orient, the present negative result should caution its users.

PMID- 16097441
TI  - Evaluation of spiral computed tomography versus ventilation/perfusion scanning in
      patients clinically suspected of pulmonary embolism.
AB  - OBJECTIVE: To prospectively evaluate the diagnostic accuracy of spiral computed
      tomography (CT) versus ventilation/perfusion (V/Q) scanning in the examination of
      patients clinically suspected of having pulmonary embolism (PE). PATIENTS AND
      METHODS: Sixty-three patients, presenting to the emergency department and
      departments of radiology and nuclear medicine of a large hospital, highly
      suspected of having PE, underwent sequential imaging testing with V/Q scanning
      and contrast-enhanced spiral CT, in addition to other clinical and laboratory
      tests. RESULTS: PE was diagnosed in 42 (66.7%) of the 63 patients. Thirty-nine of
      these 42 patients had positive findings in their CT scans, while 18 of the
      remaining 21 patients without PE had negative findings in their spiral CT
      [sensitivity, 92.9%, specificity, 85.7% Positive Predictive Value (PPV), 92.9%,
      Negative Predictive Value (NPV), 85.7%]. V/Q scans showed high-probability of PE
      in 24 of the 42 patients with PE and were negative in 9 of the remaining 21
      patients without PE (sensitivity, 571%, specificity, 42.9%, PPV, 66.7%, NPV,
      33.3%). There were statistically significant differences in specificity and
      sensitivity favoring spiral CT among men and women patients or patients > 50
      years old. Fifty-four patients (85.7%) rated their satisfaction towards spiral CT
      as 'good' or 'very good', whereas the respective rate for V/Q scanning was only
      14.3%. CONCLUSION: Spiral CT has an excellent sensitivity, specificity, PPV and
      NPV for the diagnosis of PE and it could be used as the first-line imaging
      modality in patients suspected of PE.

PMID- 16097442
TI  - Effects of eicosapentaenoic acids on oxidative stress and plasma fatty acid
      composition in patients with lupus nephritis.
AB  - Eicosapentaenoic acid (EPA) is one of the major components of fish oil, which was
      reported to have antiatherogenic, anti-inflammatory and immune suppressive
      effects. In the present study, highly purified EPA was administered to patients
      with lupus nephritis and the effects of EPA on urinary 8-isoprostane, a reliable
      marker of oxidative stress, were investigated in these patients. Six outpatients
      (1 man and 5 women), with lupus nephritis diagnosed by renal biopsy, were entered
      in the study. We administered 1800 mg EPA ethyl-ester (purity > 95%) daily and
      examined the urinary 8-isoprostane levels and plasma fatty acid composition
      before and 3 months after EPA treatment. The urinary 8-isoprostane levels were
      significantly decreased after the treatment compared with those before the
      treatment (from 530 +/- 113 pg/mg x Cr to 235 +/- 49 pg/mg x Cr, p = 0.02). The
      EPA levels in the plasma phospholipid (PL) fraction were significantly increased
      after the treatment (from 3.30 +/- 0.64 mol% to 8.01 +/- 0.47 mol%, p < 0.001).
      Arachidonic acid (AA) levels in the plasma PL fraction were significantly
      decreased after the treatment (from 9.47 +/- 0.28 mol% to 7.33 +/- 0.43 mol%, p <
      0.001). The ratios of EPA to AA were significantly increased after the treatment
      (from 0.35 +/- 0.07 to 1.14 +/- 0.16, p < 0.001). Thus, this preliminary study
      indicated that EPA might exert beneficial effects on lupus nephritis by
      decreasing the oxidative stress.

PMID- 16097443
TI  - Modulation of branching morphogenesis of fetal mouse submandibular gland by
      sodium ascorbate and epigallocatechin gallate.
AB  - As an initial step to study the effect of antioxidants on the oral environment,
      we here investigated how sodium ascorbate and (-)-epigallocatechin 3-O-gallate
      (EGCG) affect the branching morphogenesis of the fetal mouse submandibular gland
      (SMG). When mouse SMG was prepared from the embryo at 13-day post prenatal stage
      and cultured, gradual development of branching morphogenesis was observed.
      Addition of sodium ascorbate affected this morphological change in a bimodal
      fashion. At lower concentrations of sodium ascorbate (0.25 approximately 2.27
      mM), the branching morphogenesis was slightly but significantly (about 60%)
      enhanced, whereas at higher concentrations of sodium ascorbate (6.82
      approximately 10.1 mM), the branching morphogenesis was inhibited. The addition
      of EGCG failed to stimulate, but inhibited the branching morphogenesis in a dose
      dependent manner. These data support that the addition of a lower concentration
      of sodium ascorbate is essential to stimulate the growth of SMG, and that sodium
      ascorbate, but not all antioxidants, induces hormesis (beneficial action at lower
      concentration) in the present SMG system.

PMID- 16097444
TI  - Homozygosity at the C677T of the MTHFR gene is associated with increased breast
      cancer risk in the Turkish population.
AB  - BACKGROUND: Folate deficiency is implicated in cancer development. Single
      nucleotide polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene
      can modulate the effect of folate. In this case-controlled study, a possible
      effect of the common MTHFR C677T (ala-->val) polymorphism on breast cancer
      susceptibility in Turkish patients was investigated. MATERIALS AND METHODS:
      Polymorphism analysis was performed by melting curve analysis. RESULTS: The
      variant allele valine (677T) was more frequent among the patients (30.1%) than in
      controls (23.9%). This difference was weakly significant (p = 0.046; OR = 1.37)
      and due to a significantly higher frequency of the valine homozygotes (677TT)
      among the patients (12.1% vs. 5.4%; p = 0.013, OR = 2.5). Among the patients
      diagnosed at more than 40 years of age, a more pronounced association of the
      valine homozygotes with breast cancer risk was observed (p = 0.009; OR = 3.3).
      CONCLUSION: Homozygosity for the low-activity C677T genotype (TT) may represent a
      genetic determinant increasing breast cancer risk.

PMID- 16097445
TI  - The antitumor activities of flavonoids.
AB  - The flavonoids are polyphenolic compounds found as integral components of the
      human diet. They are universally present as constituents of flowering plants,
      particularly of food plants. The flavonoids are phenyl substituted chromones
      (benzopyran derivatives) consisting of a 15-carbon basic skeleton (C6-C3-C6),
      composed of a chroman (C6-C3) nucleus (the benzo ring A and the heterocyclic ring
      C), also shared by the tocopherols, with a phenyl (the aromatic ring B)
      substitution usually at the 2-position. Different substitutions can typically
      occur in the rings, A and B. Several plants and spices containing flavonoid
      derivatives have found application as disease preventive and therapeutic agents
      in traditional medicine in Asia for thousands of years. The selection of a
      particular food plant, plant tissue or herb for its potential health benefits
      appears to mirror its flavonoid composition. The much lower risk of colon,
      prostate and breast cancers in Asians, who consume more vegetables, fruits and
      tea than populations in the Western hemisphere do, raises the question of whether
      flavonoid components mediate the protective effects of diets rich in these
      foodstuffs by acting as natural chemopreventive and anticancer agents. An
      impressive body of information exists on the antitumor action of plantflavonoids.
      In vitro work has concentrated on the direct and indirect actions of flavonoids
      on tumor cells, and has found a variety of anticancer effects such as cell growth
      and kinase activity inhibition, apoptosis induction, suppression of the secretion
      of matrix metalloproteinases and of tumor invasive behavior. Furthermore, some
      studies have reported the impairment of in vivo angiogenesis by dietary
      flavonoids. Experimental animal studies indicate that certain dietary flavonoids
      possess antitumor activity. The hydroxylation pattern of the B ring of the
      flavones and flavonols, such as luteolin and quercetin, seems to critically
      influence their activities, especially the inhibition of protein kinase activity
      and antiproliferation. The different mechanisms underlying the potential
      anticancer action of plant flavonoids await further elucidation. Certain dietary
      flavonols and flavones targeting cell surface signal transduction enzymes, such
      as protein tyrosine and focal adhesion kinases, and the processes of angiogenesis
      appear to be promising candidates as anticancer agents. Further in vivo studies
      of these bioactive constituents is deemed necessary in order to develop flavonoid
      based anticancer strategies. In view of the increasing interest in the
      association between dietary flavonoids and cancer initiation and progression,
      this important field is likely to witness expanded effort and to attract and
      stimulate further vigorous investigations.

PMID- 16097446
TI  - p27(kip1) and Ki-67 (MIB1) immunohistochemical expression in radical
      prostatectomy specimens of patients with clinically localized prostate cancer.
AB  - The immunohistochemical expressions (IE) of p27(kip1) and Ki-67 (MIB-1), both
      involved in cell cycle regulation and cell proliferation, and their ability to
      predict biochemical failure, were assessed in patients with clinically localized
      prostate cancer who had underdone radical prostatectomy of curative intent. In
      addition, p27(kip1) and Ki-67 (MIB1) expressions were correlated with several pre
      operative and post-operative parameters, such as Gleason score, extracapsular
      extension, seminal vesicle involvement, pelvic lymph nodes metastasis, positive
      surgical margins, coexistence of high-grade prostatic intraepithelial neoplasia,
      tumour size, prostate volume and PSA levels. Our analysis involved 130
      consecutive radical prostatectomy specimens. A statistically significant
      correlation of low p27(kiP1) IE with seminal vesicles involvement, increased
      tumour volume and high pre-operative PSA values was documented. Low p27(kiP1) IE
      was significantly correlated with an increased likelihood of biochemical failure
      after radical prostatectomy. In addition, the increased IE of Ki-67 (MIB1)
      correlated significantly with metastatic disease in the pelvic lymph nodes and
      was a significant predictor of biochemical failure. Cox regression analysis,
      which included p27(kip1) expression, Ki-67 (MIB1) expression and all the pre
      operative and post-operative parameters, showed that pelvic lymph node
      involvement and Ki-67 (MIB1) IE were independent prognostic markers of
      biochemical failure after radical prostatectomy.

PMID- 16097447
TI  - ICSI outcome is not associated with the incidence of spermatozoa with abnormal
      chromatin condensation.
AB  - BACKGROUND: The condensation of sperm chromatin during spermiogenesis and
      epididymal transport is of essential importance for fertilization. The main
      purpose of this study was to examine whether abnormalities of sperm nuclear
      condensation can influence the outcome of intracytoplasmic sperm injection (ICSI)
      cycles. MATERIALS AND METHODS: Semen samples from 154 ICSI cycles were studied.
      Before semen preparation for ICSI, basic semen analysis was performed and a small
      portion from each sample was fixed. The condensation of sperm nuclear chromatin
      was evaluated with chromomycin A3 under a fluorescence microscope. RESULTS: The
      incidence of spermatozoa with abnormal chromatin condensation was positively
      correlated with sperm concentration (p = 0.020565), but was not correlated with
      other semen parameters such as morphology and motility. Abnormal chromatin
      condensation was also not correlated with fertilization rate, cumulative embryo
      score or pregnancy rate. CONCLUSION: The above results indicate that ICSI outcome
      is not influenced by the incidence of spermatozoa with abnormal chromatin
      condensation.

PMID- 16097448
TI  - Macrophage-associated chronic diarrhea of unknown origin. Preliminary
      observations.
AB  - The distribution of macrophages in the colonic mucosa was investigated in 13
      patients with chronic diarrhea. Group I consisted of 5 patients; both colonoscopy
      and colonic biopsies were reported as normal. Group II included 5 patients with
      normal colonoscopy, but with collagenous colitis or lymphocytic colitis at
      histology. Group III consisted of 3 patients with mucosal inflammation at both
      colonoscopy and histology. Immunostain with CD68 (a macrophage marker) revealed,
      in all patients from Group I, a linear accumulation of CD68+ macrophages at the
      top of the lamina propria. In contrast, sections from patients in Groups II and
      III showed a random distribution of CD68+ macrophages. Since all three groups of
      patients here investigated had chronic diarrhea, it goes without saying that the
      linear recruitment of macrophages in Group I may not be the direct cause of
      chronic diarrhea, as no similar linear recruitment of macrophages was
      demonstrated in patients with collagenous colitis or with chronic inflammation.
      Although the cause(s) of chronic diarrhea in patients of Group I remain to be
      elucidated, it would appear that the recruitment of macrophages along the
      superficial aspect of the lamina propria mucosa (lpm) is a characteristic
      cellular response in patients with this subtype of chronic diarrhea.

PMID- 16097449
TI  - Epidermal growth factor receptor (EGFR) expression in childhood brain tumors.
AB  - Overactivation of epidermal growth factor receptor (EGFR) signaling has been
      recognized as an important step in the pathogenesis and progression of multiple
      forms of cancer of epithelial origin. Reports regarding EGFR family members in
      brain tumors are sparse and, thus, the significance of EGFR expression in
      childhood brain tumors is unclear. In this study, the expression of the EGFR
      family members was analyzed in 22 medulloblastomas. During the
      immunohistochemical study, a sensitive, four-step, alkaline phosphatase
      conjugated antigen detection technique was employed. The results demonstrated the
      presence of c-erbB-2 (HER-2) and c-erbB-4 (HER-4) in 10 to 50% of the neoplastic
      cells of high-grade glial tumors with high immunoreactivity, while c-erbB-3 (HER
      3) was only detected in less than 10% of the neoplastically-transformed cells. In
      a follow-up, 70% of children, usually under 4 years of age, with c-erbB-2 (HER-2)
      positive MEDs/PNETs, succumbed to the cancer. The Kaplan-Meier estimation
      revealed a significant correlation between c-erbB-2 expression and survival (p =
      0.002), suggesting that c-erbB-2 (HER-2) is probably a prognostic marker for
      limited survival. Medulloblastoma is the most common malignant brain tumor that
      occurs during childhood. Multimodality treatment regimens have substantially
      improved survival in this disease; however, the tumor is incurable in about one
      third of patients with medulloblastoma, and the current treatment has a
      detrimental effect on long-term survivors. As such, the results of this study
      further support the idea that targeting EGFR alone, or in combination with its
      downstream mediators, represents a promising new approach for the management of
      childhood brain tumors. Moreover, c-erbB-2 (HER-2) expression may also be of use
      in better classifying brain tumors.

PMID- 16097450
TI  - RT-PCR expression profiling of matrix metalloproteinases and their specific
      inhibitors in cell lines and fresh biopsies of squamous cell carcinomas of the
      head and neck.
AB  - The expressions of MMP2, -7, -9, -13 and TIMP1, -2, -3 were examined in biopsies
      and cell lines of head and neck squamous cell carcinomas (HNSCC) to determine the
      association between the expression profile and TNM-staging of the primary. The
      expressions of MMP2, -7, -9, -13 and TIMP1, -2, -3 were analyzed in 30 HNSCC
      biopsies, 7 HNSCC cell lines and 1 keratinocyte cell line using RT-PCR. Negative
      correlation was determined between N-status and MMP13-RNA expression [Kendall-tau
      b -0.404 (p = 0.016), Spearman-rho -0.448 (p = 0.014)], histological grading
      [Kendall-tau-b -0.291 (p = 0.049), Spearman-rho -0,333 (p = 0.048)], and MMP7 and
      TIMP2 expression [Kendall-tau-b -0.318 (p = 0.045); Spearman-rho -0.353 (p =
      0.045)]. Positive correlation was determined between M-status and MMP9-RNA
      expression [Kendall-tau-b 0.341 (p = 0.025), Spearman-rho 0.377 (p = 0.024)] and
      MMP13 and TIMP2 expression [Kendall-tau-b 0.727 (p = 0.037), Spearman-rho 0.850
      (p = 0.016)]. The results point to a role of the tested MMPs and TIMPs in the
      metastatic spread of HNSCC.

PMID- 16097452
TI  - Foundations and private sector to enter primary care arena.

PMID- 16097451
TI  - Crisp gives NHS a year to halve PCTs in 250m pounds sterling savings drive.

PMID- 16097453
TI  - 6-month scan wait pledge aims to beat bottlenecks.

PMID- 16097454
TI  - Inspection. Sea-change in assessment puts new onus on trusts.

PMID- 16097455
TI  - On choice.

PMID- 16097456
TI  - Data briefing. Orthopaedic readmission rates.

PMID- 16097457
TI  - Sustainable Communities Awards. A sense of place.
AB  - The ingredients for sustainable communities vary. Local area agreements are
      concentrating on a core set of outcomes, which have been streamlined. PCTs should
      ideally be coterminous with the upper tier of local authorities.

PMID- 16097458
TI  - A year in Bristol. Back from the red.
AB  - United Bristol Healthcare trust has pulled back from a predicted 3.5m pounds
      sterling deficit to achieve zero balance. It faces a raft of new challenges,
      ranging from tough cancer targets to censure over waiting-list breaches. The
      trust has cut the use of nursing agencies drastically, with 95 per cent of nurses
      now bank staff. Non-clinical issues such as litter, food and the appearance of
      buildings are also being tackled.

PMID- 16097459
TI  - Clinical management. Role play.
AB  - Addenbrooke's trust in Cambridge had an acute staff shortage in radiotherapy four
      years ago. The trust enthusiastically signed up to a DoH New Ways of Working
      programme for developing radiographers. New roles helped to bring the radiography
      department to the near-full level of staffing it has today.

PMID- 16097460
TI  - Job swap. Sleeping with the enemy.

PMID- 16097461
TI  - Career mot. Is it too late for me to leap?

PMID- 16097462
TI  - Compliance with regulations.

PMID- 16097463
TI  - Keeping on the good side of HIOSH.

PMID- 16097465
TI  - Think you're HIPAA compliant? Think again.

PMID- 16097464
TI  - Dental unit water line maintenance.

PMID- 16097466
TI  - HIPAA: is your practice 'secure'?

PMID- 16097467
TI  - Record keeping: what, how and where.

PMID- 16097468
TI  - Your office computer was stolen...now what?

PMID- 16097469
TI  - The one minute geek.

PMID- 16097470
TI  - Dental samaritans give Keiki & Kupuna smiles.

PMID- 16097471
TI  - Nurses: the real solution to the health care crisis.

PMID- 16097472
TI  - What can the legislature do, to improve health care in Texas?

PMID- 16097473
TI  - Advanced practice titling.

PMID- 16097474
TI  - Safe patient handling.
AB  - No, this is not yet another story about the danger of back injuries among nurses
      and the numbers of nurses forced to leave the bedside due to limitations
      resulting from a back injury. A new twist has presented itself in the area of
      ergonomics, "Safe Patient Handling," which offers a solution to the problem
      rather than just an identification of the burden it presents to the health care
      industry. The new approach recognizes that patient transfers present clear risk
      for both the patient and the nurse; and that these risks are costly and could be
      significantly decreased or eliminated to the benefit of all concerned.

PMID- 16097475
TI  - TNA endorses statement on medical marijuana use.

PMID- 16097476
TI  - Postural control in man: the phylogenetic perspective.
AB  - Erect posture in man is a recent affordance from an evolutionary perspective.
      About eight million years ago, the stock from which modern humans derived split
      off from the ape family, and from around sixty-thousand years ago, modern man
      developed. Upright gait and manipulations while standing pose intricate
      cybernetic problems for postural control. The trunk, having an older evolutionary
      history than the extremities, is innervated by medially descending motor systems
      and extremity muscles by the more recent, laterally descending systems. Movements
      obviously require concerted actions from both systems. Research in rats has
      demonstrated the interdependencies between postural control and the development
      of fluent walking. Only 15 days after birth, adult-like fluent locomotion emerges
      and is critically dependent upon postural development. Vesttibular deprivation
      induces a retardation in postural development and, consequently, a retarded
      development of adult-like locomotion. The cerebellum obviously has an important
      role in mutual adjustments in postural control and extremity movements, or, in
      coupling the phylogenetic older and newer structures. In the human, the
      cerebellum develops partly after birth and therefore is vulnerable to adverse
      perinatal influences. Such vulnerability seems to justify focusing our scientific
      research efforts onto the development of this structure.

PMID- 16097477
TI  - Multi-joint dynamics and the development of movement control.
AB  - The movement control of articulated limbs in humans has been explained in terms
      of equilibrium points and moving equilibrium points or virtual trajectories. One
      hypothesis is that the nervous system controls multi-segment limbs by simply
      planning in terms of these equilibrium points and trajectories. The present paper
      describes a planar computer simulation of an articulated three-segment limb,
      controlled by pairs of muscles. The shape of the virtual trajectory is analyzed
      when the limb is required to make fast movements with endpoint movements along a
      straight line with bell-shaped velocity profiles. Apparently, the faster the
      movement, the more the virtual trajectory deviates from the real trajectory and
      becomes up to eight times longer. The complexity of the shape of the virtual
      trajectories and its length in these fast movements makes it unlikely that the
      nervous system plans using these trajectories. It seems simpler to set up the
      required bursts of muscle activation, coupled in the nervous system to the
      direction of movement, the speed, and the place in workspace. Finally, it is
      argued that the two types of explanation do not contradict each other: when a
      relation is established in the nervous system between muscle activation and
      movements, equilibrium points and virtual trajectories are necessarily part of
      that relation.

PMID- 16097478
TI  - Development of postural control during the first 18 months of life.
AB  - The present paper reviews the development of postural adjustments during infancy.
      In the control of posture, two functional levels can be distinguished. The basic
      level deals with the generation of direction-specific adjustments, meaning that
      dorsal muscles are primarily activated when the body sways forward, whereas
      ventral muscles are primarily activated when the body sways backward. The second
      level is involved in adaptation of the direction-specific adjustments. Postural
      development starts with a repertoire of direction-specific adjustments suggesting
      that the basic level of control has an innate origin. At first, during the phase
      of primary variability, postural activity is largely variable and can be
      minimally adapted to environmental constraints. At 3 months, postural activity
      shows a transient period during which few postural muscles participate in
      postural activity. From 6 months onward, the phase of secondary variability
      starts, during which the second level of postural control becomes functionally
      active and infants develop the ability to adapt postural activity to the
      specifics of the situation. Initially, adaptation can be accomplished in a simple
      way only, but from 9-10 months onward, it can be performed by the subtle
      adaptation of the degree of muscle contraction. Around 13-14 months, anticipatory
      postural adjustments emerge. It is concluded that the development of postural
      adjustments is characterized by four periods of transition occurring at the ages
      of 3, 6, 9-10, and 13-14 months. The major transition occurs at 6 months, when
      infants move from the phase of non-adaptive, primary variability to the phase of
      adaptive, secondary variability.

PMID- 16097479
TI  - Development of postural control in healthy children: a functional approach.
AB  - From a set of experimental studies showing how intersegmental coordination
      develops during childhood in various posturokinetic tasks, we have established a
      repertoire of equilibrium strategies in the course of ontogenesis. The
      experimental data demonstrate that the first reference frame used for the
      organization of balance control during locomotion is the pelvis, especially in
      young children. Head stabilization during posturokinetic activities, particularly
      locomotion, constitutes a complex motor skill requiring a long time to develop
      during childhood. When studying the emergence of postural strategies, it is
      essential to distinguish between results that can be explained by biomechanical
      reasons strictly and those reflecting the maturation of the central nervous
      system (CNS). To address this problem, we have studied our young subjects in
      situations requiring various types of adaptation. The studies dealing with
      adaptation of postural strategies aimed at testing short and long-term adaptation
      capacity of the CNS during imposed transient external biomechanical constraints
      in healthy children, and during chronic internal constraints in children with
      skeletal pathologies. In addition to maintenance of balance, another function of
      posture is to ensure the orientation of a body segment. It appears that the
      control of orientation and the control of balance both require the trunk as an
      initial reference frame involving a development from egocentric to exocentric
      postural control. It is concluded that the first step for children consists in
      building a repertoire of postural strategies, and the second step consists in
      learning to select the most appropriate postural strategy, depending on the
      ability to anticipate the consequence of the movement in order to maintain
      balance control and the efficiency of the task.

PMID- 16097480
TI  - Postural synergies and their development.
AB  - The recent developments of a particular approach to analyzing motor synergies
      based on the principle of motor abundance has allowed a quantitative assessment
      of multi-effector coordination in motor tasks involving anticipatory adjustments
      to self-triggered postural perturbations and in voluntary postural sway. This
      approach, the uncontrolled manifold (UCM) hypothesis, is based on an assumption
      that the central nervous system organizes covariation of elemental variables to
      stabilize important performance variables in a task-specific manner. In
      particular, this approach has been used to demonstrate and to assess the
      emergence of synergies and their modification with motor practice in typical
      persons and persons with Down syndrome. The framework of the UCM hypothesis
      allows the formulation of testable hypotheses with respect to developing postural
      synergies in typically and atypically developing persons.

PMID- 16097481
TI  - Perinatal development of the motor systems involved in postural control.
AB  - Motor behaviors of some species, such as the rat and the human baby, are quite
      immature at birth. Here we review recent data on some of the mechanisms
      underlying the postnatal maturation of posture in the rat, in particular the
      development of pathways descending from the brain stem and projecting onto the
      lumbar enlargement of the spinal cord. A short-lasting depletion in serotonin
      affects both posture and the excitability of motoneurons. Here we try to
      extrapolate to human development and suggest that the abnormalities in motor
      control observed in childhood--e.g. deficits in motor coordination--might have
      their roots in the prenatal period, in particular serotonin depletion due to
      exposure to several environmental and toxicological factors during pregnancy.

PMID- 16097482
TI  - Development of postural muscles and their innervation.
AB  - Control of posture is a prerequisite for efficient motor performance. Posture
      depends on muscles capable of enduring contractions, whereas movements often
      require quick, forceful muscle actions. To serve these different goals, muscles
      contain fibers that meet these different tasks. Muscles with strong postural
      functions mainly consist of slow muscle fibers with a great resistance against
      fatigue. Flexor muscles in the leg and arm muscles are mainly composed of fast
      muscle fibers producing relatively large forces that are rapidly fatigable.
      Development of the neuromuscular system continues after birth. We discuss in the
      human baby and in animal experiments changes in muscle fiber properties,
      regression from polyneural into mononeural innervation, and developmental changes
      in the motoneurons of postural muscles during that period. The regression of poly
      neural innervation in postural muscles and the development of dendrite bundles of
      their motoneurons seem to be linked to the transition from the immature into the
      adult-like patterns of moving and postural control.

PMID- 16097483
TI  - Cerebellar development and plasticity: perspectives for motor coordination
      strategies, for motor skills, and for therapy.
AB  - The role of the mammalian cerebellum ranges from motor coordination, sensory
      motor integration, motor learning, and timing to nonmotor functions such as
      cognition. In terms of motor function, the development of the cerebellum is of
      particular interest because animal studies show that the development of the
      cerebellar cortical circuitry closely parallels motor coordination.
      Ultrastructural analysis of the morphological development of the cerebellar
      circuitry, coupled with the temporal and spatial identification of the
      neurochemical substrates expressed during development, will help to elucidate
      their roles in the establishment of the cerebellar circuitry and hence motor
      activity. Furthermore, the convenience of a number of naturally occurring mouse
      mutations has allowed a functional dissection of the various cellular elements
      that make up the cerebellar circuitry. This understanding will also help in the
      approach to possible therapies of pathologies arising during development because
      the cerebellum is especially prone to such perturbation because of its late
      development.

PMID- 16097484
TI  - Role of the basal ganglia in balance control.
AB  - In this review paper, we summarize the important contributions of the basal
      ganglia to the regulation of postural control. After a brief overview of basal
      ganglia circuitries, the emphasis is on clinical observations in patients with
      focal lesions in parts of the basal ganglia, as the impairments seen here can
      serve to highlight the normal functions of the basal ganglia nuclei in postural
      control. Two particularly relevant functions are discussed in detail: first, the
      contribution of the basal ganglia to flexibility and to gaining control of
      balance-correcting responses, including the ability to lend priority to the
      elements of a postural task; and second, processing afferent information by the
      basal ganglia, which is increasingly recognized as being highly relevant for
      postural control.

PMID- 16097485
TI  - Postural behavior in children born preterm.
AB  - The present paper presents clinical and neurophysiological data of postural
      behavior in preterm children without CP. Clinical follow-up studies of preterm
      infants until toddler and school age have reported that low-risk preterm infants
      may have atypical postural behavior in terms of reduced amount of rotation during
      crawling, delayed dynamic balance, delayed onset of and a poor quality of early
      walking behavior. At school age, dysfunctions such as problems in standing on one
      leg and poor hopping are reported. Neurophysiological data of postural control at
      early age indicated the presence of a dysfunction in the capacity to modulate
      postural activity, and the postural activity has been characterized by temporal
      disorganization of EMG responses. Postural responses to goal-directed reaching in
      supine lying have been recorded and analyzed in terms of the total body center of
      pressure. In this study, preterm infants show less mobile postural behavior
      compared with full-term infants. In infancy, the less mobile postural behavior
      seemed to be adequate as it was related to better goal-directed reaching quality,
      but the results indicated that the relatively immobile postural behavior during
      reaching in early age was related to less favorable neuromotor behavior in school
      age.

PMID- 16097486
TI  - Postural control in children with developmental coordination disorder.
AB  - The development of static balance is a basic characteristic of normal motor
      development. Most developmental motor tests include a measure of static balance.
      Children with Developmental Coordination Disorder (DCD) often fail this item.
      This study reviews the balance problems of children with DCD. The general
      conclusion is drawn that under normal conditions static balance control is not a
      problem for children with DCD. Only in difficult, unattended, or novel situations
      such children seem to suffer from increased postural sway. These findings raise
      the question of what happens when balance is lost. The present study addresses
      the strength of correlation between the electromyography (EMG) and force plate
      signals in one-leg stance over epochs of stable and unstable balance. Four groups
      of children were involved in the study: two age groups and a group of children
      with DCD and balance problems and their controls. The results show a clear
      involvement of tibialis anterior and peroneus muscles in the control of lateral
      balance in all conditions and groups. The group of children with DCD and balance
      problems, however, showed a weaker coupling between EMG and corrective force
      compared with control children, indicating non-optimal balance control. An
      evaluation of the existing data in terms of evidence of specific structural
      deficits associated with DCD provided converging evidence that suggests
      cerebellar involvement.

PMID- 16097487
TI  - Postural muscle dyscoordination in children with cerebral palsy.
AB  - The present paper gives an overview of the knowledge currently available on
      muscular dyscoordination underlying postural problems in children with cerebral
      palsy (CP). Such information is a prerequisite for developing successful
      therapeutic interventions in children with CP. Until now, three children with CP
      functioning at GMFCS (Gross Motor Function Classification System) level V have
      been documented. The children totally or partially lacked direction specificity
      in their postural adjustments and could not sit independently for more than 3
      seconds. Some children functioning at GMFCS level IV have intact direction
      specific adjustments, whereas others have problems in generating consistently
      direction-specific adjustments. Children at GMFCS levels I to III have an intact
      basic level of control but have difficulties in fine-tuning the degree of
      postural muscle contraction to the task-specific conditions, a dysfunction more
      prominently present in children with bilateral spastic CP than in children with
      spastic hemiplegia. The problems in the adaptation of the degree of muscle
      contraction might be the reason that children with CP, more often than typically
      developing children, show an excess of antagonistic coactivation during difficult
      balancing tasks and a preference for cranial-caudal recruitment during during
      reaching. This might imply that both stereotypies might be regarded as functional
      strategies to compensate for the dysfunctional capacity to modulate subtly
      postural activity.

PMID- 16097488
TI  - Role of visual dysfunction in postural control in children with cerebral palsy.
AB  - INTRODUCTION: Deficient postural control is one of the key problems in cerebral
      palsy (CP). Little, however, is known about the specific nature of postural
      problems of children with CP, nor of the relation between abnormal posture and
      dysfunction of the visual system. AIM OF THE STUDY: To provide additional
      information on the association of abnormalities in postural control and visual
      dysfunction of the anterior or posterior part of the visual system. METHODS: Data
      resulting from ophthalmologic, orthoptic, neurological, neuro-radiological, and
      ethological investigations of more than 313 neurologically impaired children were
      retrospectively analyzed. RESULTS: Abnormal postural control related to ocular
      and ocular motor disorders consisted of anomalous head control and subsequent
      abnormal head posture and torticollis. The abnormal postural control related to
      retrochiasmatical damage of the visual system consisted of a torticollis combined
      with adjustment of the upper part of the body, as if at the same time adapting to
      a combination of defects and optimizing residual visual functions. CONCLUSION:
      Visual dysfunctions play a distinct role in the postural control of children with
      CP.

PMID- 16097489
TI  - Postural dysfunction during standing and walking in children with cerebral palsy:
      what are the underlying problems and what new therapies might improve balance?
AB  - In this review we explore studies related to constraints on balance and walking
      in children with cerebral palsy (CP) and the efficacy of training reactive
      balance (recovering from a slip induced by a platform displacement) in children
      with both spastic hemiplegic and diplegic CP. Children with CP show (a) crouched
      posture, contributing to decreased ability to recover balance (longer
      time/increased sway); (b) delayed responses in ankle muscles; (c) inappropriate
      muscle response sequencing; (d) increased coactivation of agonists/antagonists.
      Constraints on gait include (a) crouched gait; (b) increased co-activation of
      agonists/antagonists; (c) decreased muscle activation; (d) spasticity. The
      efficiency of balance recovery can be improved in children with CP, indicated by
      both a reduction in the total center of pressure path used during balance
      recovery and in the time to restabilize balance after training. Changes in muscle
      response characteristics contributing to improved recovery include reductions in
      time of contraction onset, improved muscle response organization, and reduced co
      contraction of agonists/antagonists. Clinical implications include the suggestion
      that improvement in the ability to recover balance is possible in school age
      children with CP.

PMID- 16097490
TI  - Postural dysfunction in children with cerebral palsy: some implications for
      therapeutic guidance.
AB  - Postural problems play a central role in the motor dysfunction of children with
      cerebral palsy (CP). Therefore, they spend more time in sitting than in standing
      to perform vital tasks of daily life. The focus of this article is to describe
      the pathophysiology of postural control in sitting and outline some implications
      for management and treatment. In general, children with CP exhibit muscular
      activity counteracting forces that disturb equilibrium. Only 'non-sitting'
      children with severe CP lack such 'direction-specific' adjustments, possibly
      ruling out achievement of independent sitting. Most frequently, the children
      display dysfunctions in the adaptation of the adjustment. Typical characteristics
      of this adaptation in children with CP are a top-down recruitment of postural
      muscles, an excessive degree of antagonistic coactivation, and an incomplete
      adaptation of the EMG-amplitude to task specific constraints. Despite our
      knowledge on the pathophysiology underlying the postural problems in children
      with CP, little 'high-level' evidence (according to Sackett) exists on how
      different interventions can affect these problems. Therapeutic attention to
      promote motor performance in sitting focuses on adaptive seating, tilting of the
      support surface, and ample, variable training in motivating settings. The
      challenge facing us now is to provide evidence about the efficacy of specific
      treatment approaches facilitating that children reach an optimal level of
      functioning in daily life.

PMID- 16097491
TI  - Efficacy and effectiveness of physical therapy in enhancing postural control in
      children with cerebral palsy.
AB  - The purpose of this article was to conduct a systematic review of studies that
      examined the efficacy and effectiveness of postural control intervention
      strategies for children with CP. Only physical therapy interventions were
      included, e.g. adaptive seating devices, ankle foot orthoses, neurodevelopmental
      treatment. A multifaceted search strategy was employed to identify all potential
      studies published between 1990 and 2004. The search strategy included electronic
      databases, reference list scanning, author and citation tracking of relevant
      studies, and hand searching of pediatric physical therapy journals and conference
      proceedings. Twelve studies (1991-2004), comprising ten group design studies and
      two single subject studies, met our inclusion criteria. A variety of age ranges
      and severity of children with cerebral palsy (n=132) participated in the studies.
      The study quality scores ranged from 2 to 7 (total possible range of 0 to 7) with
      a median score of 5.5 and a mode of 6. As was true in an earlier systematic
      review on adaptive seating, most of the 12 'experimental' studies published since
      1990 that were aimed at evaluating the effectiveness of postural control
      strategies provided lower levels of evidence, i.e. Sackett Levels III to V.
      Additional studies with stronger designs are needed to establish that postural
      control interventions for children with CP are effective.

PMID- 16097492
TI  - A critical review of constraint-induced movement therapy and forced use in
      children with hemiplegia.
AB  - Hemiplegia is a physical impairment that can occur in childhood following head
      trauma, cerebral vascular accident or transient ischemic attack (stroke), brain
      tumor, or congenital or perinatal injury. One of the most disabling symptoms of
      hemiplegia is unilaterally impaired hand and arm function. Sensory and motor
      impairments in children with hemiplegia compromise movement efficiency. Such
      children often tend not to use the affected extremity, which may further
      exacerbate the impairments, resulting in a developmentally learned non-use of the
      involved upper extremity, termed 'developmental disuse'. Recent studies suggest
      that children with hemiplegia benefit from intensive practice. Forced use and
      Constraint-Induced Movement Therapy (CI therapy) are recent therapeutic
      interventions involving the restraint of the non-involved upper extremity and
      intensive practice with the involved upper extremity. These approaches were
      designed for adults with hemiplegia, and increasing evidence suggests that they
      are efficacious in this population. Recently, forced use and constraint-induced
      therapy have been applied to children with hemiplegia. In this review, we provide
      a brief description of forced use and CI therapy and their historical basis,
      provide a summary of studies of these interventions in children, and discuss a
      number of important theoretical considerations, as well as implications for
      postural control. We will show that whereas the studies to date suggest that both
      forced use and CI therapy appear to be promising for improving hand function in
      children with hemiplegia, the data are limited. Substantially more work must be
      performed before this approach can be advocated for general clinical use.

PMID- 16097493
TI  - Factors involved in the migration of neuroendocrine hypothalamic neurons.
AB  - Neuroendocrine control of physiological functions needs a complex developmental
      organisation of the hypothalamic parvicellular neurons, which synthesise and
      release hypophysiotropic hormones. Among the hypothalamic neuroendocrine cells,
      Gonadotropin-releasing hormone (GnRH) neurons represent a unique class; they are
      generated in the olfactory placode and, during embryonic life, migrate to the
      septo/hypothalamic region along terminal and vomeronasal nerves. At this level
      GnRH neurons undergo terminal differentiation and start to release GnRH to
      modulate the secretion of pituitary gonadotropins. All these steps are under the
      strict control of several developmental cues and their defect might represent a
      cause of clinical disorders. A number of factors have been proposed to be
      involved in the migration of GnRH neurons, but their role is still unclear. By
      using gene knockout techniques it has been found that mice carrying a targeted
      deletion of Ebf2 gene, a component of Olf/Ebf bHLH transcription factors, show a
      defective migration of GnRH neurons, providing the first evidence of a mouse
      model of such defect. Since the investigation of GnRH neurons is hindered by
      their peculiar anatomical distribution, other studies has been forwarded by the
      availability of immortalized GnRH-expressing neurons (GN11 cells) that retain a
      strong chemomigratory response "in vitro". Among the factors analysed, we found
      that hepatocyte growth factor/scatter factor (HGF/SF) and vascular endothelial
      growth factor (VEGF) induce specific chemotaxis of GN 11 neurons, suggesting that
      migratory signals can arise from nasal mesenchyme and from the concomitant
      vasculogenesis. Finally, anosmin-1 (the product of the gene responsible of the X
      linked form of Kallmann's disease) was found to induce a significant chemotactic
      response of GN11 cells, confirming a permissive/instructive role of KAL1 gene
      product in the migratory behaviour of GnRH neurons. In conclusion, the migration
      of the GnRH neurons appears to be a complex process, which involves the interplay
      of multiple molecular cues. These studies may provide new insights on the
      etiopathogenesis of the large proportion of reproductive dysfunctions that affect
      humans and could provide novel insights on common biochemical events controlling
      neuronal development and migration.

PMID- 16097494
TI  - Transgenic models for studying expression and function of axonal adhesive
      glycoproteins.
AB  - In this study, by using two transgenic models, we address the general topic of
      the significance of axonal glycoproteins regulated expression in nervous tissue
      maturation. The immunoglobulin superfamily components F3/Contactin (F3) and TAG-1
      are used as the molecular models in this respect. First, a minigene including the
      relevant regulatory sequences of the F3 gene, deduced by a previous in vitro
      study, has been fused to an EGFP (Enhanced Green Fluorescent Protein) reporter
      and expressed in transgenic mice, which provided information about the profile of
      F3 gene developmental activation. In a complementary model, transgenic mice have
      been generated which express the F3 cDNA under control of a selected regulatory
      region from the TAG-1 gene. While leading to ectopic expression of F3, this
      perturbed neuronal precursor proliferation and differentiation. The arising
      effects were even stronger than those coming from the overall suppression of the
      F3 or, respectively, TAG-1 genes, thus supporting the hypothesis that the
      mechanisms underlying axonal glycoprotein regulated expression are themselves
      endowed with a key significance in neural development.

PMID- 16097495
TI  - Neuropeptides and retinal development.
AB  - Different peptidergic systems have been investigated with some detail during
      retinal development, including substance P (SP), vasoactive intestinal
      polypeptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP) and
      somatostatin (SRIF). Concerning possible developmental actions of neuropeptides,
      VIP and PACAP exert protective and growth-promoting actions that may sustain
      retinal neurons during their development. In addition, the presence of transient
      SRIF expressing cells and recent observations in SRIF receptor knock out mice
      indicate variegated roles of this peptide in the development of the retina and of
      retinofugal projections. Finally, recent studies have shown that, in the
      developing rabbit retina, changes in the expression pattern of SP receptors are
      accompanied by modifications of SP physiological effects, indicating that retinal
      circuits where SP is involved are likely to function in a substantially different
      manner before the retina becomes involved in the processing of visual stimuli. SP
      neurotransmission in the immature retina may subserve developmental events, and
      SP is likely to represent an important developmental factor for the maturation of
      retinal neurons and circuitries.

PMID- 16097496
TI  - A dynamic population of excitable cells: the taste receptor cells.
AB  - Taste receptor cells (TRCs) represent an unique opportunity to study a dynamic
      population of excitable cells that undergoes two basic neurobiological processes:
      postnatal development and cell turnover. We have begun to investigate the
      functional properties of TRCs and how they mature over time by applying the patch
      clamp technique to single cell in taste buds isolated from mouse vallate papilla
      during postnatal development. We have focussed our attention on a well-defined
      functional group of taste cells, called Na/OUT cells, and on their voltage-gated
      K+, and Cl- currents (I(K) and I(Cl), respectively). As in neurons, I(K) and
      I(Cl) underlie action potential waveform and firing properties in these cells. By
      analyzing the relative occurrence of I(K) and I(Cl) among cells, we found that in
      adult mice three different electrophysiological phenotypes of Na/OUT cells could
      be detected: cells with only I(K) (K cells); cells with both I(K) and I(Cl) (K +
      Cl cells); and cells with I(Cl) (Cl cells). On the contrary, at early
      developmental stages (2-4 postnatal day, PD) there were no Cl cells, which
      appeared at PD 8. The analysis of the changes in current amplitude (which
      continuously increased in developing cells) during postnatal development
      suggested that Cl cells and K + Cl cells likely represented a single functional
      line different from K cells. In addition, electrophysiological data were
      consistent with the interpretation that Cl cells derived from some K + Cl cells
      by suppression of I(K). The dynamics of the expression of I(K) and I(Cl) during
      postnatal development likely reflects a mechanism that could also operate during
      turnover.

PMID- 16097497
TI  - Central nervous mechanisms in the generation of the pattern of breathing.
AB  - The role of the Botzinger complex (BotC) and the pre-Botzinger complex (pre-BotC)
      in the genesis of the breathing pattern was investigated in anesthetized,
      vagotomized, paralysed and artificially ventilated rabbits making use of
      bilateral microinjections of kainic acid (KA) and excitatory amino acid (EAA)
      receptor antagonists. KA microinjections into either the BotC or the pre-BotC
      transiently eliminated respiratory rhythmicity in the presence of tonic phrenic
      activity (tonic apnea). Rhythmic activity resumed as low-amplitude, high
      frequency irregular oscillations, superimposed on tonic inspiratory activity and
      displayed a progressive, although incomplete recovery. Microinjections of
      kynurenic acid (KYN) and D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) into the
      BotC caused a pattern of breathing characterized by low-amplitude, high-frequency
      irregular oscillations and subsequently tonic apnea. Responses to KYN and D-AP5
      in the pre-BotC were similar, although less pronounced than those elicited by
      these drugs in the BotC and never characterized by tonic apnea. Microinjections
      of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) into the BotC and the pre-BotC
      induced much less intense responses mainly consisting of increases in respiratory
      frequency. The results show that the investigated medullary regions play a
      prominent role in the genesis of the normal pattern of breathing through the
      endogenous activation of EAA receptors.

PMID- 16097498
TI  - Cardiorespiratory interactions to external stimuli.
AB  - Respiration is a powerful modulator of heart rate variability, and of baro- or
      chemo-reflex sensitivity. This occurs via a mechanical effect of breathing that
      synchronizes all cardiovascular variables at the respiratory rhythm, particularly
      when this occurs at a particular slow rate coincident with the Mayer waves in
      arterial pressure (approximately 6 cycles/min). Recitation of the rosary prayer
      (or of most mantras), induces a marked enhancement of these slow rhythms, whereas
      random verbalization or random breathing does not. This phenomenon in turn
      increases baroreflex sensitivity and reduces chemoreflex sensitivity, leading to
      increases in parasympathetic and reductions in sympathetic activity. The opposite
      can be seen during either verbalization or mental stress tests. Qualitatively
      similar effects can be obtained even by passive listening to more or less
      rhythmic auditory stimuli, such as music, and the speed of the rhythm (rather
      than the style) appears to be one of the main determinants of the cardiovascular
      and respiratory responses. These findings have clinical relevance. Appropriate
      modulation of breathing, can improve/restore autonomic control of cardiovascular
      and respiratory systems in relevant diseases such as hypertension and heart
      failure, and might therefore help improving exercise tolerance, quality of life,
      and ultimately, survival.

PMID- 16097499
TI  - Cardioventilatory responses during real or imagined walking at low speed.
AB  - There is increasing evidence that motor imagery involves at least in part central
      processes used in motor control. In order to deepen our understanding on the
      neural mechanisms underlying vegetative responses to real and imagined exercise,
      we determined cardioventilatory variables during actual or imagined treadmill
      walking on flat terrain at speeds of 2, 3.5 or 5 km/h, in a group of 14 healthy
      volunteers. During actual walking, as expected, a comparable intensity-dependent
      increase was found in ventilation, oxygen consumption, tidal volume and
      respiratory rate. Imagined walking led to a significant, albeit small (less than
      10%), increase in ventilation and oxygen consumption, and to larger increases (up
      to 40%) in respiratory rate, which was paralleled by a non significant trend
      towards a decline of tidal volume. These results confirm and extend previous
      observations showing that motor imagery is accompanied by centrally induced
      changes in vegetative responses, and provide evidence for a differential control
      on respiratory rate and tidal volume.

PMID- 16097500
TI  - Sarcopenia is more than a muscular deficit.
AB  - Sarcopenia is a complex process that appears in aged muscle associated with a
      decrease in mass, strength, and velocity of contraction. This process is the
      result of many molecular, cellular and functional alterations. It has been
      suggested that sarcopenia may be triggered by reactive oxygen species (ROS) that
      have accumulated throughout one's lifetime. We found a significant increase in
      oxidation of DNA and lipids in the elderly muscle, more evident in males, and a
      reduction in catalase and glutathione transferase activities. Experiments on Ca2+
      transport showed an abnormal functional response of aged muscle after exposure to
      caffeine, which increases the opening of Ca2+ channels, as well a reduced
      activity of the Ca2+ pump in elderly males. From these results we concluded that
      oxidative stress play an important role in muscle aging and that oxidative damage
      is much more evident in elderly males, suggesting a gender difference may be
      related to hormonal factors. The progression of sarcopenia is directly related to
      a significant reduction of the regenerative potential of muscle normally due to a
      type of adult stem cells, known as satellite cells, which lie outside the
      sarcolemma and remain quiescent until external stimuli trigger as growth factors
      (IGF-1 or mIGF-1) their re-entry into the cell cycle. One possibility is that the
      anti oxidative capacity of satellite cells could also be altered and this, in
      turn, determines the decrease of their regenerative capacity. Data concerning
      this hypothesis are discussed

PMID- 16097501
TI  - Cell therapy of primary myopathies.
AB  - Mesoangioblasts are multipotent progenitors of mesodermal tissues. In vitro
      mesoangioblasts differentiate into many mesoderm cell types, such as smooth,
      cardiac and striated muscle, bone and endothelium. After transplantation
      mesoangioblasts colonize mostly mesoderm tissues and differentiate into many cell
      types of the mesoderm. When delivered through the arterial circulation,
      mesoangioblasts significantly restore skeletal muscle structure and function in a
      mouse model of muscular dystrophy. Their ability to extensively self-renew in
      vitro, while retaining multipotency, qualifies mesoangioblasts as a novel class
      of stem cells. Phenotype, properties and possible origin of mesoangioblasts are
      addressed in the first part of this paper. In the second part we will focus on
      the cell therapy approach for the treatment of Muscular Dystrophy and we will
      describe why mesangioblasts appear to be promising candidates for this strategy.

PMID- 16097502
TI  - Growth factor enhancement of muscle regeneration: a central role of IGF-1.
AB  - The prolongation of skeletal muscle strength in aging and neuromuscular disease
      has been the objective of numerous studies employing a variety of approaches. In
      the last decade, dramatic progress has been made in elucidating the molecular
      defects underlying a number of muscle diseases. With the characterization of
      mutations responsible for muscle dysfunction in several inherited pathologies,
      and the identification of novel signaling pathways, subtle alterations in which
      can lead to significant defects in muscle metabolism, the field is poised to
      devise successful strategies for treatment of this debilitating and often fatal
      group of human ailments. Yet progress has been slow in therapeutic applications
      of our newly gained knowledge. The complexity of muscle types, the intimate
      relationship between structural integrity and mechanical function, and the
      sensitivity of skeletal muscle to metabolic perturbations have impeded rapid
      progress in successful clinical intervention. The relatively poor regenerative
      properties of striated muscle compound also the devastating effects of muscle
      degeneration.

PMID- 16097503
TI  - European Surveillance of Antibiotic Consumption (ESAC): Ireland has lessons to
      learn.

PMID- 16097504
TI  - The management of Bell's palsy.

PMID- 16097505
TI  - Primary total hip replacement--a survey of current practice and identifying
      changing trends.
AB  - Primary total hip replacement (THR) surgery is the most commonly performed and
      successful reconstructive procedure in orthopaedic surgery. We performed a survey
      of Irish Orthopaedic consultants to elucidate current practices of primary THR in
      elderly and young patients and identify changing trends. There was an 83%
      response rate. Most respondents use a cemented THR in elderly patients. 69% use a
      different THR in younger patients compared to older patients. 9% refer younger
      patients to hip replacement specialist consultant colleagues. 70% report changing
      to a new implant or new technique in younger patients and 45% use a hybrid THR,
      15% an uncemented THR, 15% perform hip resurfacing and 47% use different bearing
      surfaces. Only 17% use the Charnley hip prosthesis in younger patients. Young and
      active patients will place high demands on a new THR and newer techniques,
      implants and bearing surfaces are being adopted in the hope of better outcomes.

PMID- 16097506
TI  - Gait abnormalities in older people--comparison of inter-professional assessment.
AB  - Gait abnormalities are common in older people but relatively under-diagnosed. We
      investigated the prevalence of gait abnormalities among patients presenting to a
      geriatric medicine day hospital, classified them according to whether they were
      lower, middle or higher level gait disorders and compared inter-professional
      (physician and physiotherapist) assessments for this classification. Prospective
      independent assessment by a physician and a senior physiotherapist of 50
      consecutive patients presenting to a day hospital. Presence of a gait abnormality
      was determined and then classified. Levels of agreement were determined between
      the two professions. There was 98% agreement that a gait abnormality existed in
      43 people. In classifying the gait abnormality there was complete agreement in
      over two-thirds of cases (67.4%). There was further agreement of higher level
      gait disorders (but disagreement in the sub-classification) in 11.6% of cases.
      Given the high prevalence of gait abnormality presenting to the day hospital,
      screening for gait and balance disorders should be of paramount importance. While
      levels of agreement between the two professions were high, disagreement existed
      in approximately one-third of cases. Agreement among professionals essential for
      appropriate tailoring of treatment and intervention.

PMID- 16097507
TI  - Admission to neonatal intensive care with respiratory morbidity following 'term'
      elective caesarean section.
AB  - Delaying the timing of elective caesarean section (ELCS) from 37/38 weeks to
      39/40 weeks reduces the risk of respiratory morbidity in otherwise healthy
      neonates. The aims of this study were to clarify the number and clinical details
      of term infants delivered by ELCS who were admitted to neonatal intensive care
      (NIC) from 1st April 2001 to 31st March 2002 in Northern Ireland, to record the
      level of care required by these infants and to identify infants who were
      diagnosed with transient tachypnoea of the newborn (TTN) and/or Respiratory
      Distress Syndrome (RDS). Two hundred and ten (8%) of babies born by ELCS were
      admitted to NIC. Term infants delivered by ELCS used 343 days of level 1 & 2 care
      with 230 (68%) of these days being used by infants with RDS/TTN (n=105) the
      majority of whom were delivered at 37/38 weeks. Definitions of 'term' and
      clinical indications for ELCS urgently need to be debated to avoid unnecessary
      morbidity following ELCS in so called 'term' infants.

PMID- 16097508
TI  - Validating the Orpington Prognostic Score in an Irish in-patient stroke
      population.
AB  - An accurate assessment of stroke severity and the ability to predict prognosis is
      important for determining rehabilitation needs and long term management of
      patients after stroke. The Orpington Prognostic Score (OPS) is a clinically
      derived stroke severity scale that can be used to stratify patients into
      different severity groups. The aim of this study was to validate the Orpington
      Prognostic Score (OPS) in an Irish in-patient stroke population. Fifty 'first
      stroke' patients (21 male, median age 72.5 [range 31-93] years) were assessed
      within two weeks following stroke onset. Subjects were stratified into mild,
      moderate and severe groups using previously established cut-offs for the OPS.
      Outcomes were determined prospectively and compared to initial severity groups.
      Patients in the severe group had a significantly increased chance of dying (Odds
      ratio [95%CI] 2.16 [1.72-2.72] and this persisted after adjustment for age and
      gender. Length of stay increased significantly with increasing stroke severity
      group (F ratio 7.0 p=0.0025) and this association remained after adjusting for
      age and gender. The odds of being discharged home or of being able to walk
      independently by time of discharge decreased significantly (all p<0.001) as
      stroke severity increased and adjusting for age and gender did not alter these
      associations. A higher OPS score within 2 weeks of stroke onset was significantly
      associated with longer length of stay, increased mortality, reduced mobility at
      discharge and a reduced likelihood of discharge home. The OPS is a valid measure
      of stroke severity in Irish stroke in-patients.

PMID- 16097509
TI  - Morbidity and mortality following inadvertent poisoning with decanted chemicals.
AB  - Decanting of chemicals from their original containers is a hazardous practice
      that can result in inadvertent poisoning. We conducted a four-year prospective
      observational study to analyse the epidemiology of accidental poisoning with
      decanted chemicals. 157 patients were poisoned following accidental exposure to
      chemicals transferred to innocuous containers. 106 patients attended hospital
      emergency departments, 17 attended a general practitioner and 34 were instructed
      to seek medical advice if symptomatic. 112 patients developed clinical features,
      9 patients required admission to intensive care and 4 of these needed intubation
      and ventilation. There was 1 fatality following inadvertent ingestion of
      paraquat. The predominant symptoms were gastrointestinal upset and a burning
      sensation in the mouth, throat, and stomach. Decanted chemicals included
      household, industrial, automobile, and agricultural products. Caustic agents
      accounted for approximately 33% of decanted chemicals. Decanting of chemicals
      into innocuous containers results in significant morbidity, mortality, and cost
      to the health service.

PMID- 16097510
TI  - Hospitalisations due to falls in older persons.
AB  - This paper describes hospitalisations due to falls among people aged 65 years and
      over resident in the Eastern Region of Ireland. Of the 2,029 hospitalisations
      recorded for 2002, 78% were female and 68% were aged 75 years and over. Fractures
      accounted for 1,697 or 84% of cases with nearly half of them (841) sustained to
      the hip. Females were more likely to have a limb fracture whereas males were more
      likely to have a head injury. The total inpatient costs of the 2,029
      hospitalisations were estimated at 10.6 million euros. Hip fractures were the
      costliest injuries as they accounted for 7.4 million euros (70%) of inpatient
      costs. There are also substantial additional costs implications for hip fractures
      as they constituted the majority (56%) of cases transferred to
      nursing/convalescent homes or long-stay health facilities. In keeping with an
      ageing population, the problem of injuries in older people is likely to increase
      over time and as falls are the dominant cause of those injuries, all acute and
      long-stay health facilities need to develop and implement fall prevention
      strategies for older people.

PMID- 16097511
TI  - Cutaneous sarcoidal reaction in a patient with pulmonary tuberculosis.
AB  - Sarcoidosis is a systemic disorder characterized by non-caseating epithelioid
      granulomas that may affect any organ system. The etiology of sarcoidosis is
      unknown, but several immune aberrations are thought to play a role in its
      pathogenesis. The possible role of mycobacterial infection in the pathogenesis of
      sarcoidosis has been suggested. In recent studies mycobacterial DNA was detected
      in lung tissues and bronchial lavage fluid of 30% to 50% of patients with
      sarcoidosis. We report a patient with pulmonary tuberculosis treated successfully
      three years earlier who developed cutaneous sarcoidosis with negative polymerase
      chain reaction (PCR) assay for mycobacterial DNA of the skin lesion.

PMID- 16097512
TI  - Meralgia paraesthetica following open appendicectomy.
AB  - Meralgia paraesthetica is a painful condition attributed to entrapment or injury
      to the lateral femoral cutaneous nerve. It has been described following
      operations which could result in direct injury to the nerve such as iliac crest
      bone harvesting. It has also been reported following surgery remote from the
      nerve. Following open appendicectomy injury may occur following direct trauma to
      an anatomical variant of this nerve, which can occur in up to 25% of the
      population. We report two cases that became clinically evident immediately
      following open appendicectomy with subsequent confirmatory electromyography
      studies. Meralgia paraesthetica following open appendicectomy has not been
      reported in the medical literature. This is an under-recognised complication of
      open appendicectomy. Management can be challenging for patient and clinician.

PMID- 16097513
TI  - Auxology and growth assessment.

PMID- 16097514
TI  - An unusual case of an arteriobiliary fistula.

PMID- 16097515
TI  - Cardiovascular risk and anaesthesia: what is an anaesthetist to think?

PMID- 16097516
TI  - Optimal intraoperative haemodynamic management.

PMID- 16097517
TI  - Preoperative evaluation of cardiac risk.

PMID- 16097518
TI  - Perioperative beta-blockade: does it improve outcome?

PMID- 16097519
TI  - Alcohol dependence and treatment strategies.

PMID- 16097520
TI  - Suprapubic catheters: indications and complications.

PMID- 16097521
TI  - Modernising medical careers: is it good for patients?

PMID- 16097522
TI  - Strategies and tactics for effective prescribing during the foundation year.

PMID- 16097523
TI  - Emergency management of the unconscious patient.

PMID- 16097524
TI  - Interpretation of the chest radiograph in the casualty department.

PMID- 16097525
TI  - How to intubate.

PMID- 16097526
TI  - Injuries to the distal radius.

PMID- 16097527
TI  - So you want to be ... a psychiatrist.

PMID- 16097528
TI  - Cardiac resynchronization therapy: the procedure and progress so far.

PMID- 16097529
TI  - Delirium in the elderly.

PMID- 16097530
TI  - Career intentions of preregistration house officers and the influence of career
      advice.

PMID- 16097531
TI  - Death of a pioneer surgeon.

PMID- 16097532
TI  - Late presentation of traumatic rupture of the right hemidiaphragm.

PMID- 16097534
TI  - Protect your pension fund from a punitive new tax.

PMID- 16097533
TI  - A sting in the tail of Hurricane Charley.

PMID- 16097535
TI  - Research during surgical training: why are we doing it?

PMID- 16097536
TI  - Patients with unsafe swallowing: look out for bedside hazards.

PMID- 16097537
TI  - Patient-controlled analgesia: does one regimen fit all?

PMID- 16097538
TI  - Hip dysplasia and osteoarthrosis: a survey of 4151 subjects from the
      Osteoarthrosis Substudy of the Copenhagen City Heart Study.
AB  - INTRODUCTION: Hip dysplasia (HD) is assumed to be an etiological factor in the
      development of premature hip osteoarthrosis (OA). We established the prevalences
      of HD and OA in adults according to qualified radiographic discriminators, and
      investigated the relationship between HD and OA. METHODS: Wiberg's CE angle (CE),
      Sharp's angle, the femoral head extrusion index, the acetabular depth ratio
      (ADR), the radiographic OA discriminators of Croft, and of Kellgren and Lawrence,
      and also minimum joint space width (JSW) < or = 2 mm were applied to the
      standing, standardized pelvic radiographs of 1429 men (22-93 years), and 2430
      women (22-92 years). RESULTS: The 4 HD discriminators were interrelated. A
      negligible sex-related difference in acetabular morphology was found, male
      acetabulae being slightly more dysplastic than female acetabulae. However,
      differences between the sexes for right and left CE angles were within 1.0
      degree, and within 1.4 degrees for right and left Sharp's angles. There were no
      cases of hip subluxation (breakage of Shenton's line > or = 5 mm). Average CE
      angle was 34 degrees in men (SD 7.3 degrees), and 35 degrees in women (SD 7.6
      degrees). Applying a CE cut-off value of 20 degrees for designation of definite
      hip dysplasia, we found a prevalence of hip dysplasia of 3.4%. Approximately 2%
      of cases were unilateral and 1.4% of cases were bilateral. We found significant
      relationships between radiographic OA discriminators and the CE angle, femoral
      head extrusion index and ADR. Odds ratios ranged from 1.0 to 6.2. Compared to
      subjects with OA in morphologically normal hips, a trend towards younger age in
      subjects with HD and OA was noted, but this was not strictly significant.
      INTERPRETATION: We found that HD is not uncommon in the general population. The
      assumption that HD is an etiological factor in the development of hip OA was
      confirmed.

PMID- 16097539
TI  - Migration of the acetabular component: effect of cement pressurization and
      significance of early radiolucency: a randomized 5-year study using
      radiostereometry.
AB  - BACKGROUND: Cementing technique is a crucial factor in prosthesis fixation. No
      randomized studies have been published, however, comparing the outcome of
      conventional fingerpacking with the outcome of pressurization of the cement prior
      to cup insertion. PATIENTS AND METHODS: We randomized 50 THAs to either
      fingerpacking or sequential pressurization (including individual pressurization
      of each anchorage hole) and followed the patients with RSA for 5 years. The
      penetration of cement into the anchorage holes was measured on digital
      radiographs. Postoperative radiolucent lines around the cup were correlated to
      later RSA results. For clinical evaluation, we used SF-36 and HHS. RESULTS: The
      pressurized group of THAs was more stable regarding changes in inclination. We
      found no other difference in the migratory behavior. The cement penetration into
      the anchorage holes was deeper with the pressurization technique than with
      fingerpacking. For the whole group taken together, there was a strong relation
      between the presence of radiolucent lines as measured on the postoperative
      radiograph and later migration observed by RSA at 2 and 5 years. INTERPRETATION:
      Pressurization of the cement produced better cement penetration and increased the
      cup stability in terms of changes in inclination. Early findings of radiolucent
      lines can predict later unfavorable cup migration.

PMID- 16097540
TI  - Poor results from the isoelastic total hip replacement: 14-17-year follow-up of
      149 cementless prostheses.
AB  - BACKGROUND: To overcome the mismatch between a stiff stem and the more elastic
      bone, the concept of isoelasticity was introduced in the 1970s. This concept was
      based on the assumption that the implant and the bone should deform as one unit
      to avoid stress shielding. The Robert Mathys (RM) cementless total hip
      replacement (THR) was one of the earliest isoelastic designs. PATIENTS AND
      METHODS: From 1984 to 1987, we performed 149 total hip replacements in 135
      patients (92 women, mean age 47 (21-72) years) using third-generation Mathys
      isoelastic polyacetal stem with stainless-steel heads and polyethylene cementless
      acetabular cups. 11 patients died before revision or before the examination for
      this study, and 14 were lost to follow-up. Average follow-up time for the
      remaining 110 patients was 15 (14-17) years. RESULTS: To date, 69 hips (64
      patients) have been revised, 5 due to infection. The 10-year survival rate for
      any reason was 70% (66-74). In the 46 remaining patients (53 hips), the average
      HHS was 80 (39-100) points. 13 of these were regarded as radiographic failures,
      with an average HHS of 75 points. INTERPRETATION: The performance of this
      prosthesis was unacceptably poor. Higher debris production and poor primary
      fixation are believed to be the main reason for the high failure rate.

PMID- 16097541
TI  - A reliable DEXA measurement technique for metal-on-metal hip resurfacing.
AB  - INTRODUCTION: Dual energy X-ray absorptiometry (DEXA) has been used to measure
      bone mineral density (BMD) around total hip prostheses. With the recent increase
      in the use of metal-on-metal hip resurfacing, such as the Birmingham hip
      resurfacing (BHR), we aimed to produce a reliable method of measuring bone
      density around a metal-on-metal hip resurfacing. METHODS: We performed DEXA scans
      on 5 patients (7 BHRs), who had undergone resurfacing with the BHR within the
      past 2 years. A zonal reporting technique was devised and evaluated. RESULTS: The
      intraclass correlation (i.e. the correlation between any two assessments of one
      region of interest) was 0.997, with an overall coefficient of variation of 5%.
      INTERPRETATION: We have designed and demonstrated a safe, noninvasive and highly
      reproducible method for interpreting and reporting the results of DEXA scanning
      of BHR implants in vivo. We will now use this method to prospectively study our
      BHR population to assess the changes in bone density following BHR within the
      femoral neck. This method may add to the current techniques available for
      detection of impending failure.

PMID- 16097542
TI  - Total hip arthroplasty in Denmark: incidence of primary operations and revisions
      during 1996-2002 and estimated future demands.
AB  - BACKGROUND: The annual number of total hip arthroplasties (THA) has increased in
      Denmark over the past 15 years. There is, however, limited detailed data
      available on the incidence of THAs. METHODS: We calculated the incidence rates
      (IR) of primary THA and revision in Denmark between 1996 and 2002 and estimated
      the demands for primary THA in Denmark until 2020. We used data from the Danish
      Hip Arthroplasty Registry, a nationwide and population-based clinical database,
      to identify patients who had undergone primary THA (n = 37,144) or revision
      arthroplasties (n = 6446). Age and sex-specific data on the Danish population
      were obtained from the StatBank Denmark. All IRs were standardized according to
      two standards, i.e. the Danish population in 1996 and the European standard
      population (18 age groups). The future demands for primary THA were estimated
      using the age and sex-specific incidence of primary THA for 2002 as a reference,
      and taking into account the expected changes in the age distribution of the
      population and the trend in IRs seen in Denmark between 1996 and 2002. RESULTS:
      The annual overall standardized IRs of primary THAs and revisions increased from
      101 (95% confidence interval (CI): 97.6-104) to 134 (CI: 131-138) and from 19.2
      (CI: 17.9-20.5) to 21.1 (CI: 19.8-22.4) per 100,000 inhabitants from 1996 to
      2002, respectively (IRs adjusted to the Danish population in 1996). The IRs of
      primary THAs and revisions increased by 30% and 10% during this period. The
      relative increase in IRs of primary THAs was found to be similar in both women
      and men. The increase was higher among patients aged 50-59 years, however.
      Furthermore, a decrease in IRs was seen in patients who underwent primary THA due
      to rheumatoid arthritis. IRs of primary THAs have been estimated to increase by
      22% in 2020 compared with 2002, based only on the expected changes in the age
      distribution of the population. However, assuming that the annual age and sex
      independent increase in the IRs seen in the period 1996-2002 will continue, the
      IR of primary THA is estimated to increase by as much as 210% in 2020.
      INTERPRETATION: The overall annual standardized IRs of primary THAs and revisions
      in Denmark increased during the period from 1996 to 2002. Moreover, the demands
      for THA procedures in the coming decades may exceed the current capacity due to
      the ageing population and a continued age and sex-independent increase in
      surgical activity.

PMID- 16097543
TI  - Excellent results from proximally HA-coated femoral stems with a minimum of 6
      years follow-up: a prospective evaluation of 100 patients.
AB  - BACKGROUND: There have been few reports on the mid- and long-term follow-up
      results of the proximally HA-coated femoral stem. We evaluated this type of stem
      prospectively, with 6-12 years of follow-up. METHODS: The survival rate, Harris
      hip score and radiographic features of 106 hips in 100 consecutive patients were
      evaluated. The mean age at operation was 51 years (SD 8.2). RESULTS: The mean
      Harris hip score at the time of the latest follow-up was 95 points. Spot welds
      occurred in 95% of the patients and were first observed at a mean follow-up of
      1.4 years in one or more of the Gruen regions, corresponding to the coated part
      of the femoral stem. A higher grade of stress shielding correlated with a less
      favorable Harris hip score and pain subscore. According to the criteria of Engh,
      all stems were graded as stable and durable bone-ingrown. No femoral component
      was revised. INTERPRETATION: At an average follow-up of 8 years, this proximally
      HA-coated femoral component showed favorable clinical and radiological outcome
      and excellent survivorship.

PMID- 16097544
TI  - Total hip arthroplasty in patients with human immunodeficiency virus infection:
      pathologic findings and surgical outcomes.
AB  - BACKGROUND: An increased incidence of osteonecrosis of the femoral head has been
      reported in patients infected with human immunodeficiency virus (HIV). The
      purpose of this study was to review the pathologic specimens of HIV-positive
      patients who had undergone total hip arthroplasty (THA) and compare them with
      those of THA patients who were HIV-negative. The surgical outcomes of these HIV
      positive patients were also reviewed. METHODS: 40 HIV-positive patients who
      underwent 54 THAs at our institution were identified. The primary pathologic
      diagnosis for the femoral heads of these patients was osteonecrosis in 35 cases,
      degenerative joint disease in 11 cases, and other diagnoses in 8 cases. RESULTS:
      There was a higher incidence of osteonecrosis in HIV-positive patients. At the
      most recent follow-up, 4 patients had died and 1 patient had a significant
      Staphylococcus aureus infection of the hip. INTERPRETATION: There was a
      significant difference in the pathologic diagnoses of the HIV-positive group and
      the HIV-negative group, implicating HIV infection as a risk factor for
      osteonecrosis. Also, the risk of infectious complications is lower in our study
      than previously reported in other studies of HIV-positive patients who have
      undergone THA.

PMID- 16097545
TI  - The "Oxford Heup Score": the translation and validation of a questionnaire into
      Dutch to evaluate the results of total hip arthroplasty.
AB  - BACKGROUND: The evaluation of a total hip prosthesis would be most complete if
      the opinion of the patient, surgeon and the radiographs are combined. Disease
      specific patient outcome questionnaires are scarce, especially in Dutch. METHODS:
      The disease-specific 12-item questionnaire on the perception of patients with
      total hip replacement was translated into Dutch. We also investigated the extra
      value of two specific hip items, "the need for walking aids" and "sexual problems
      because of the hip", four general items on overall satisfaction and one question
      about patient classification. The 14 hip-specific items were each scored from 1
      (least difficulties) to 5 (most difficulties). The Dutch translation, the "Oxford
      Heup Score" (OHS) was tested on psychometric quality in a multicenter prospective
      study. RESULTS: The psychometric results of the OHS proved to be adequate. In the
      first postoperative year the score was very sensitive to changes, whereas in the
      second year it did not change significantly. The two added hip-specific questions
      were both filled out positively by more than 50% of the patients and thus fit
      perfectly into a hip-specific patient outcome questionnaire such as the OHS.
      INTERPRETATION: The OHS proves to be an appropriate instrument for assessment of
      the outcome of total hip replacement from the patient's perspective. Together
      with the judgement of the surgeon, it provides useful insights into the question
      of whether this operation has been a success or not.

PMID- 16097546
TI  - One-stage treatment of congenital severely dislocated hips in older children
      through various acetabuloplasty techniques: 22 children followed for 1-5 years.
AB  - BACKGROUND: There is no consensus regarding the best treatment for children with
      late diagnosis of congenital hip dislocation. PATIENTS AND METHODS: This
      retrospective study involved 29 hips in 22 children (19 girls) with an age range
      of 3-14 years, who had been operated with various techniques for congenital hip
      dislocation between 1998 and 2002. 6 patients had right, 9 patients had left, and
      7 patients had bilateral congenital hip dislocation. The mean length of follow-up
      was 3 (1-5) years. RESULTS: While the mean acetabular index was 53 degrees (35
      65) preoperatively, at the last follow-up it was 30 degrees (15-50). 27 hips were
      type 4 and 2 hips were type 3 by Tonnis criteria. Satisfactory reduction (Severin
      Class I) had been achieved in 19 hips at the follow-up radiography, and they
      developed no osteonecrosis. The outcome was successful in children under 7 years
      of age, but problems encountered in those over 7 increased unless sufficient
      reduction had been achieved. INTERPRETATION: Age at treatment of late-diagnosed
      congenital hip dislocation appears to be important for outcome.

PMID- 16097547
TI  - Articular cartilage defects in a rabbit model, retention rate of periosteal flap
      cover.
AB  - BACKGROUND: A periosteal flap is frequently used in procedures involving repair
      of articular cartilage defects. Hypertrophy of the repair tissue, probably from a
      retained periosteum, is a clinical problem but not much is known about this
      issue. The objective of the present experimental study was to investigate the
      retention rate of periosteal flaps with respect to various postoperative
      mobilization regimes and the introduction of bone marrow elements underneath the
      flap. METHOD: We created a chondral lesion (diameter 4 mm) in both patellas of 18
      New Zealand white rabbits. The subchondral bone was left intact in one knee. In
      the other, the bone plate was perforated, allowing bone marrow elements to enter
      the defect. All defects were covered with a periosteal flap, sutured and glued to
      the rim of the cartilage defect. Postoperatively, the rabbits were allocated to
      one of three groups: A. rehabilitation in cages for 4 days, then killed; B.
      rehabilitation in cages for 7 days, then free activity on the floor of a 10 m2
      room until the end of the second week, then killed; C. rehabilitation in cages
      for 2 weeks, then killed. RESULTS: 16 of 23 periosteal flaps became detached
      within 2 weeks (one knee was excluded because of clinical signs of infection),
      with no difference in the retention rate with respect to mobilization regime or
      established access to bone marrow elements in the defect. The periosteum still
      served as a cover of the defect in 10 of 12 knees at day 4. This figure decreased
      to 7 of 23 knees at day 14. CONCLUSION: Our study is the first to document the
      retention rate of periosteal flaps in a rabbit model. The low retention rate
      observed may explain why periosteal hypertrophy is not reported in experimental
      studies where the periosteal flap is sutured to the cartilage rim.

PMID- 16097548
TI  - The influence of ultrasound on the mechanical properties of healing tendons in
      rabbits.
AB  - BACKGROUND: Therapeutic ultrasound is commonly used for treatment of injuries to
      tendons, ligaments and joint capsules. Opinions still differ, however, as to the
      beneficial effects of ultrasound treatment of the above-mentioned conditions.
      METHODS: We studied the effect of various ultrasound intensities on the healing
      of tenotomized, sutured and immobilized Achilles tendons of adult rabbits.
      Different intensities of pulsating ultrasound (0, 50, 100, 200, 500, 750, 1000
      and 2000 mW/cm2, frequency 3 MHz) were given over the healing tendons for 5 min
      daily, using a gel as the coupling agent between the ultrasound probe and the
      skin. Eleven days after the tenotomy, the healing tendons were analyzed in a
      materials testing machine. RESULTS: The extensibility of the healing tendons was
      greater after sonication at an intensity of 2000 mW/cm2 than after 50 mW/cm2. We
      found no significant effect on the load at rupture and normalized load at rupture
      of the ultrasound-treated healing tendons compared with mock-sonicated healing
      tendons. A gradual decline was observed, however, in the stiffness and collagen
      content of the healing tendons with increasing intensity of the ultrasound
      treatment. INTERPRETATION: The pulsating ultrasound treatment applied did not
      improve the mechanical properties of healing Achilles tendons at day 11 after the
      operation. On the other hand, a slight decline in stiffness was observed with
      increasing intensity of ultrasound treatment.

PMID- 16097549
TI  - Effect of gamma irradiation on the osteoinductivity of morphogenetic protein
      extract from reindeer bone.
AB  - BACKGROUND: Bone morphogenetic proteins (BMPs), which are capable of stimulating
      the production of new bone, must be sterilized before preclinical and clinical
      use to reduce the risk of infections and associated complications. In this study,
      we investigated the effects of gamma sterilization on the osteoinductivity of
      native reindeer BMP extract in the Balb/C mouse thigh muscle pouch model.
      METHODS: 5 mg of native reindeer BMP extract and 5 mg of bovine serum albumin
      were administered separately either in gelatine capsules or mixed with gelatine
      as injections. The dose of gamma irradiation was 4.1 Mrad. Unsterile capsules and
      injections served as controls. New bone formation was evaluated based on the
      incorporation of Ca45 and also radiographically 3 weeks after implantation.
      RESULTS: Albumin-containing implants and injections did not induce new bone
      formation, as monitored in radiographs. Gamma sterilization did not reduce the
      osteoinductivity of native BMP extract in capsules, but a significant decrease in
      osteoinductivity--measured as area (50%) and Ca45 incorporation of new bone (27%)
      -was seen after injection. Gamma sterilization had no effect on the optical
      density of new bone induced by native BMP extract administered in capsules or by
      injection. INTERPRETATION: We conclude that, as gamma irradiation did not reduce
      the osteoinductivity of reindeer BMP extract in gelatine capsules, this method
      appears to be suitable for sterilization of BMPs to be given in capsule form.
      Native reindeer BMP extract was more sensitive to irradiation in soluble collagen
      (gelatine) than BMP in gelatine capsules. This finding must be given serious
      consideration regarding treatment of patients, but the remaining activity may be
      sufficient for the induction of bone formation in preclinical and clinical
      situations.

PMID- 16097550
TI  - The biceps tendon footprint.
AB  - BACKGROUND: By arthroscopy, we observed a phenomenon that, according to our
      knowledge not previously described, we call the "biceps tendon footprint" (BTF)-
      an area of chondromalacia beside the bicipital groove. PATIENTS AND METHODS: We
      studied 118 shoulder arthroscopies prospectively. We documented whether a BTF
      could be observed and what the main pathology associated with it was. We used 3
      grades of cartilage wear to describe BTF, and we analyzed pathological changes in
      associated structures (subscapularis, biceps tendon and humeral head). RESULTS:
      We found a BTF in 16% of the cases. Associated diagnoses were cuff tears and
      instabilities, most often multidirectional. We observed all 3 grades of cartilage
      wear, grade 3 being the commonest. Biceps synovitis occurred more often in the
      BTF group. INTERPRETATION: BTF is not a rare phenomenon. Maltraction of the
      intraarticular biceps tendon in MDI and cuff tears in addition with biceps
      synovitis appear to cause BTF.

PMID- 16097551
TI  - Rotator cuff tears associated with os acromiale.
AB  - INTRODUCTION: Os acromiale is a rare anatomical condition; its incidence in
      cadaver studies has been found to be approximately 8%. In this retrospective
      study we investigated the incidence and types of os acromiale in patients with
      rotator cuff tears. METHODS: We assessed operation notes and axillary radiographs
      for the presence and the type of os acromiale in 1000 consecutive patients with
      open rotator cuff repairs. RESULTS: 62 patients (6.2%) showed an os acromiale in
      the axillary radiographs. In 6 of these the os acromiale was not described in the
      operation notes. 57 os meso-acromiale and 5 os pre-acromiale were found. The
      average number of tendons involved in the cuff tear was the same (1.4) in
      patients with and without os acromiale. The average age of patients with os
      acromiale was 55 years, and 56 years in patients without os acromiale.
      INTERPRETATION: Os acromiale is a co-condition in patients with rotator cuff
      tear. The prevalence of os acromiale in patients with rotator cuff tear is
      similar to that in a standard population with unknown integrity status of the
      rotator cuff. Thus, it seems debatable whether an os acromiale is a pathological
      condition leading to rotator cuff tears.

PMID- 16097552
TI  - Femoral lengthening over an intramedullary nail using the external fixator: risk
      of infection and knee problems in 22 patients with a follow-up of 2 years or
      more.
AB  - BACKGROUND: The time for femoral lengthening is shortened if external fixation is
      combined with intramedullary nailing. However, several complications have been
      reported with this procedure. PATIENTS AND METHODS: We retrospectively reviewed
      the outcome of femoral lengthening performed over an intramedullary nail using
      external fixation in 22 patients. These patients were followed for a mean of 3.2
      (2-5.2) years. The mean age was 22 (13-35) years at the time of the index
      procedure. The mean lengthening was 5 (2.7-8.1) cm and the external fixator was
      removed after median 20 (8-30) weeks. The mean external fixation index was 24 (11
      35) days/cm and the mean consolidation index was 43 (26-55) days/cm of
      lengthening. RESULTS: 3 patients who had a past history of infection or open
      trauma developed osteomyelitis which required removal of the nail. There were 4
      knee joint complications when the lengthening was over 20%, including posterior
      knee subluxation and patella subluxation. In 1 patient, the lengthened segment
      collapsed with breakage of locking screws. INTERPRETATION: Although lengthening
      over a nail can reduce the duration of external fixation, caution is required to
      prevent major complications.

PMID- 16097553
TI  - Changed gait pattern in patients with total knee arthroplasty but minimal
      influence of tibial insert design: gait analysis during level walking in 39 TKR
      patients and 18 healthy controls.
AB  - INTRODUCTION: Previous radiostereometric studies have revealed abnormal anterior
      posterior translation of the femur in patients operated with AMK (DePuy, Johnson
      and Johnson, Leeds, UK) total knee arthroplasty (TKA). Based on these
      observations, we hypothesized that patients with TKA have an abnormal gait
      pattern, and that there are differences in kinematics depending on the design of
      the tibial joint area. METHOD: We used a gait analysis system to evaluate the
      influence of joint area design on the kinematics of the hip and knee during level
      walking. 39 TKA patients (42 knees) and 18 healthy age-matched controls were
      studied. Patients with 5 degrees varus/valgus alignment or less were randomized
      to receive either a relatively flat or a concave tibial insert with retention of
      the posterior cruciate ligament. Patients who had more than 5 degrees varus
      valgus alignment and/or extension defect of 10 degrees or more were randomized to
      receive the concave or a posterior-stabilized tibial component with resection of
      the posterior cruciate ligament. RESULTS: Patients with TKA tended to have less
      hip and knee extension and decreased knee and hip extension moment than controls.
      They also tended to walk more slowly. TKA altered the gait pattern, but choice of
      implant design had little influence. INTERPRETATION: In patients with a similar
      degree of degenerative joint disease and within the limits of the constraints
      offered by the prostheses under study, the choice of joint area constraint has
      little influence on the gait pattern.

PMID- 16097554
TI  - Tibial lengthening and concomitant foot deformity correction in 14 patients with
      permanent deformity after poliomyelitis.
AB  - BACKGROUND: In neuromuscular diseases, limb lengthening and foot deformity
      correction are associated with a high risk of complications associated with
      distraction callus and joint contracture. We have found no published articles of
      tibial lengthening and concomitant foot deformity correction using the Ilizarov
      method or traditional methods. To compare result of gradual distraction with
      triple arthrodesis for foot deformity combined with tibial lengthening, we
      investigated healing index and complications of two methods. PATIENTS AND
      METHODS: We reviewed 14 patients with permanent deformity after poliomyelitis who
      underwent tibial lengthening and concomitant foot deformity correction using the
      Ilizarov external fixator. Tibial lengthening over an intramedullary nail was
      performed in 3 patients and lengthening without a nail was performed in 11
      patients. RESULTS: The mean external fixation time was 6 (3.6-10) months without
      nail and 1.6 (1.5-1.7) months with nail, whereas the mean healing index was 1.8
      (0.8-3.1) months/cm without nail and 2 (1.8-2.3) months/cm with nail. Concomitant
      foot treatments included triple arthrodesis in 7 patients, pantalar arthrodesis
      in 2 patients with flail ankle, and gradual foot frame distraction without bony
      foot procedures in 5 patients. Delayed consolidation and recurrent equinus
      contracture of the ankle requiring additional lengthening of the Achilles tendon
      were the most common bone and joint complications during tibial lengthening.
      INTERPRETATION: The gradual foot frame distraction method was associated with
      major complications, such as recurrent foot deformity, joint luxation, and
      arthritis. We therefore recommend triple arthrodesis as a concomitant procedure
      during tibial lengthening

PMID- 16097555
TI  - Gross osteolytic tibia tunnel widening with the use of Gore-Tex anterior cruciate
      ligament prosthesis: a radiological, arthrometric and clinical evaluation of 17
      patients 13-15 years after surgery.
AB  - BACKGROUND: Postoperative widening of the bone tunnels have been found after
      anterior cruciate ligament reconstruction using autologus bone-patellar tendon
      bone or hamstring tendon grafts. These changes seem to be of no clinical
      significance in a short to midterm follow-up. We investigated if a synthetic
      graft evokes the same bone tunnel widening and if it is of clinical significance
      in a longterm follow-up. METHODS: We examined 17 patients, 13-15 years after
      their anterior cruciate ligament reconstruction using a Gore-Tex ligament
      prosthesis. The follow-up consisted of clinical examination, K-1000 arthrometric
      measurement, Tegner, Lysholm and IKDC scores, and CT examination of their tibia
      bone tunnels. 6 patients had been reoperated before follow-up, 3 because of graft
      rupture and 3 because of effusion and/or pain. RESULTS: 5 patients were graded as
      normal (n = 2) or nearly normal according to the IKDC score, and 4 of these
      patients still had their Gore-Tex prosthesis intact. 15 of the patients had a
      tibia bone tunnel wider than the drilled 7.9 mm diameter, ranging from 9.6 to 26
      mm. These changes in the bone tunnels were in some cases without symptoms and
      could not be detected with arthroscopy, clinical examination, arthrometry or
      evaluation scores. We do not know whether they are progressive. INTERPRETATION:
      Based on our findings, we recommend that patients who have had a Gore-Tex
      anterior cruciate ligament reconstruction should be examined not only clinically
      or by questionnaire, but also with CT.

PMID- 16097556
TI  - The economic cost of low back pain in Sweden in 2001.
AB  - BACKGROUND: Low back pain (LBP) is a common cause of lost work days and
      disability. In 2001, expenditure for back pain represented 11% of the total costs
      for short-term sick leave in Sweden, and about 13% of all early retirement
      pensions were granted for back problems, of which LBP is the most important
      symptom. The magnitude of LBP as a health problem justifies a closer look at its
      burden of illness to society. MATERIALS AND METHODS: We assessed the costs of LBP
      to society in Sweden in 2001. The study was conducted in a cost-of-illness
      framework, measuring both the direct costs of providing health care to LBP
      patients, and the indirect costs as the value of the production that is lost
      because people are too ill to work. The costs were estimated by a prevalence and
      top-down approach. RESULTS: The total cost of LBP was 1860 million EUR in Sweden
      in 2001. The indirect costs due to lost productivity accounted for 84% of the
      total cost. INTERPRETATION: The cost of illness due to low back pain was
      substantial, but does not appear to have risen during the last 10-15 years.

PMID- 16097557
TI  - Academic clinical oncology and radiobiology research network (ACORRN): an NCRI
      initiative to address the infrastructure and capacity deficit in radiotherapy and
      radiobiology research in the UK.

PMID- 16097558
TI  - Technology enhancements and changes in radiotherapy throughput in New South
      Wales.
AB  - AIMS: To assess the effect that the age of linear accelerators and recent changes
      in technology have had on linear accelerator throughput in New South Wales,
      Australia. MATERIALS AND METHODS: Duration was measured (time of patient entry
      into the treatment room to time of exit) of each radiotherapy treatment fraction
      delivered on each linear accelerator over a 5-day period. Patient-, treatment-
      and equipment-based variables were collected for all treatment fractions, and
      assessed for their effect on fraction duration. Comparisons were made between
      these data and similar productivity data collected from a study carried out in
      1996. Since the sample sizes for both the study periods were large enough, the
      distributions of the means were assumed normal (Central Limit Theorem). Specific
      analyses were carried out to assess the affect that new technologies, such as
      automatic field-sequencing (AFS) and multi-leaf collimator (MLC), have had on
      fraction duration. RESULTS: A total of 12 892 treatment fields and 4316 treatment
      fractions were delivered on 27 linear accelerators over 135 days. Comparison
      between the 2003 and 1996 productivity data showed an increase in the mean number
      of patients treated per hour by 11% and fields treated per hour by 31%. The mean
      number of fields treated per fraction increased by 15%. The mean fraction
      duration was reduced by 13% for linear accelerators of less than the median age
      of 7 years that were equipped with MLC/AFS, or both, compared with older linear
      accelerators without AFS and MLC. This reduction was more obvious for complex
      techniques, such as four-field breast treatments (27% decrease in fraction
      duration). The mean number of fields treated per hour was 43% more on the newer
      machines equipped with AFS and MLC. CONCLUSIONS: An increase in productivity has
      been observed between the 1996 and 2003 study periods, as measured by patients or
      fields per hour, despite an increase in treatment complexity as measured by
      fields per fraction. The application of AFS and MLC, and the use of newer linear
      accelerators, significantly shortened the mean duration per fraction for the
      common treatment techniques.

PMID- 16097559
TI  - The development of a new basic treatment equivalent model to assess linear
      accelerator throughput.
AB  - AIMS: The basic treatment equivalent (BTE) model was developed in 1996 in an
      attempt to improve the measurement of linear accelerator throughput in
      radiotherapy. This study aimed to assess the effect of treatment set-up and
      patient characteristics on fraction duration, to update the BTE model and to
      determine the better throughput measure between fields per hour and BTE per hour.
      MATERIALS AND METHODS: Stopwatch measurements of the duration of each
      radiotherapy treatment fraction delivered on each linear accelerator in
      participating New South Wales radiation oncology departments over a 5-day period
      in 2003 were undertaken. Patient, equipment and staff data were collected to
      assess the effect of these variables on fraction duration. A new BTE equation was
      derived, including the most significant variables. Statistical comparison of
      fields and BTE per unit time was made to assess the better predictor of fraction
      duration. RESULTS: Data collected on 27 linear accelerators in 13 departments
      included a total of 135 days of linear accelerator operation, 4316 fractions and
      12 892 treatment fields. Seventeen factors significantly influenced fraction
      duration (P < 0.01). These accounted for 46% of the total variance in the models.
      The eight most influential predictors of prolonged fraction duration were
      included in the BTE model. These were as follows: high number of fields, high
      number of port films/electronic portal imaging, absence of automatic field
      sequencing and multi-leaf collimation, high number of junctions, use of bolus and
      first fraction of a treatment course. The BTE per hour was shown to be a better
      predictor of throughput than fields per hour. CONCLUSIONS: The BTE model is a
      better measure of linear accelerator throughput. It incorporates weightings for
      treatment and patient factors that significantly influenced fraction duration.
      This measure could be routinely collected by the radiation oncology departments
      and included in the electronic radiotherapy information systems.

PMID- 16097560
TI  - The MRC randomised-controlled trial of interferon-alpha, interleukin-2 and 5
      fluorouracil vs interferon-alpha alone in patients with advanced renal cell
      carcinoma (RE04): rationale and progress.

PMID- 16097561
TI  - Testicular sex cord-stromal tumours: the Edinburgh experience 1988-2002, and a
      review of the literature.
AB  - AIMS: Sex cord-stromal tumours of the testis are uncommon tumours, accounting for
      around 5% of testicular neoplasms. Treatment is primarily surgical, with no
      adjuvant therapy of proven benefit. We present a single-centre experience over a
      period of 15 years. MATERIALS AND METHODS: From 1988 to 2002, 18 patients with a
      diagnosis of sex cord-stromal tumour were referred to our centre. A retrospective
      analysis of their case notes was made and a pathological review undertaken.
      RESULTS: Sixteen were Leydig-cell tumours and two were Sertoli cell. For the
      Leydig-cell tumours, the median age at presentation was 42 years, 50% presented
      with a testicular mass and 31% with gynaecomastia. Two patients followed a
      malignant course: one revealing disease dissemination at initial staging, and a
      second 12 months after potentially curative orchidectomy. Salvage retroperitoneal
      lymphadenectomy in the latter patient proved unsuccessful. Clinical outcome
      correlated strongly with the presence of adverse pathological features described
      previously in the literature. After a median follow-up of 46 months, two patients
      have developed progressive disease, and two patients have died, one of metastatic
      Leydig-cell tumour. No patient defined as being of low malignant potential on
      pathological examination has relapsed outside our review period of 2 years.
      CONCLUSION: We confirm the overall excellent prognosis for most of the patients
      with sex cord-stromal tumours of the testis. Compared with most previous reports,
      pathological features seem to predict with reasonable accuracy the risk of
      malignant behaviour, and can adequately inform the subsequent review policy.

PMID- 16097562
TI  - GRiN: a trial and tribulation in respiratory radiotherapy research.

PMID- 16097563
TI  - A phase I study of moderate-dose radiation therapy and weekly gemcitabine in
      patients with locally advanced non-small cell lung cancer not suitable for
      radical chemoradiation therapy.
AB  - AIMS: To describe the toxicity and response seen in patients receiving moderate
      dose radiation therapy with concurrent weekly low-dose gemcitabine in the
      management of locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND
      METHODS: Eighteen patients with confirmed NSCLC were enrolled over a 17-month
      period from August 2000 until January 2002. All had localised disease but were
      considered unsuitable for curative therapy. Radiation therapy was given to a dose
      of 30 Gy in 15 fractions over 3 weeks. Gemcitabine was given weekly before and
      within 3 h of fractions 1, 6 and 11. The study was designed as a dose-escalation
      study, commencing at 100 mg/m2 and increasing at levels of 50 mg/m2, until the
      maximum tolerated dose (MTD) was reached. RESULTS: The MTD was regarded as being
      150 mg/m2. The major acute toxicity observed was oesophagitis. Skin reactions
      were also reported. The overall response rate in all patients was 88%, with 44%
      achieving a complete response. CONCLUSION: The combination of gemcitabine and
      moderate-dose radiation therapy is feasible, and offers low toxicity and
      excellent response rates in patients with localised NSCLC not suitable for high
      dose therapy.

PMID- 16097564
TI  - Verification films: a study of the daily and weekly reproducibility of breast
      patient set-up in the START trial.
AB  - AIMS: Verification of patient position in radiotherapy by the use of portal
      images is a current practice in most radiotherapy departments. All patients
      within the Standardisation of Breast Radiotherapy Trial (START) were required to
      have on-treatment verification images. Measurements of maximum lung and breast
      depth from these were used to provide details for the case-report forms. This
      study was undertaken to validate these measurements, assess the reproducibility
      of patients' set-up within the START trial and to compare reproducibility on a
      day-to-day basis with reproducibility over a longer period. Analysis also
      included a subjective assessment of image quality. MATERIALS AND METHODS: Fifty
      three patients from 29 departments were studied. Some centres used electronic
      portal imaging and others used film. Where film verification was the method of
      choice, information was collected about the type of film and cassette used.
      RESULTS: The correlation coefficients for inter- and intra-observer variability
      of breast and lung depth were 0.99. Comparing maximum breast depth on weekly and
      daily images, the median per cent standard deviation of breast depth was 4% and
      3%, respectively. The mean standard deviation of breast depth for all patients,
      which gives an indication of the individual patient variability, was 5.5 +/- 2.2
      mm for weekly and 3.9 +/- 1.5 mm for daily measurements. For lung depth, mean
      standard deviation was 6.8 +/- 2.5 mm for weekly and 6.8 +/- 2.8 mm for daily
      measurements. Images taken using Kodak X-omat V film were inferior to those taken
      with films in corresponding cassettes. CONCLUSION: Differences between lung depth
      measured in simulator and on the treatment unit were evident for many patients.
      There was little difference in the standard deviations of breast and lung depth
      for daily and weekly verification films on the treatment machine.

PMID- 16097565
TI  - Intensity-modulated radiotherapy planning from limited anatomical information: is
      Sim-CT sufficient for planning women with breast cancer receiving intensity
      modulated radiotherapy?
AB  - AIMS: To investigate intensity-modulated radiotherapy (IMRT) plans for women with
      carcinoma of the breast, using a small number of Sim-CT slices, thus avoiding
      changing the patient's position and potential problems with CT capacity.
      MATERIALS AND METHODS: Ten CT scans of women with breast cancer were obtained for
      use in the study. IMRT plans based on an open tangent pair and additional top-up
      segment fields were created using the full CT scan, and represented the gold
      standard treatment plan for comparison purposes. Five-slice CT simulator scans
      were artificially created by omitting intermediate slices from the full CT scans.
      Additionally, the intermediate CT slices were recreated via interpolation of the
      five slices using a standard interpolation algorithm. IMRT plans were created in
      the same way as for the full CT scans. To allow a suitable plan comparison to be
      made, the beam segments and monitor units were transferred to the full CT scans,
      and the dose distribution calculated. RESULTS: The interpolated five-slice plans
      showed no significant difference in the volume of tissue receiving dose outside
      the range 95-105%, compared with the IMRT plans created using the full CT data
      set (1.3 +/- 2.2%, P = 0.092). In contrast, the discrete slice CT simulator plans
      increased by 6.3 +/- 5.4%, P = 0.0054, showing a statistically significant
      difference in the dose distribution produced and a clinically inferior plan.
      CONCLUSIONS: Plans created using five discrete slice CT scans were inferior to
      full CT-derived IMRT treatment plans, and are therefore not acceptable for IMRT.
      However, interpolating five CT simulator slices provides adequate anatomical
      information to produce comparable IMRT plans to those created by full CT scans of
      the patient. This allows the introduction of IMRT for this patient group without
      the need to change treatment position to accommodate CT scanning.

PMID- 16097566
TI  - An audit of postoperative radiotherapy after non-curative resection for cancer of
      the oesophagus.
AB  - AIMS: The role of postoperative radiotherapy (PORT) after non-curative resections
      for cancer oesophagus is not well defined. A policy of offering PORT after non
      curative resections for cancer oesophagus has been followed at our institution,
      and we report an audit of our experience. MATERIAL AND METHODS: Between March
      1990 and September 2002, 139 patients underwent resections for cancer oesophagus.
      Of these, 86 patients received PORT to a dose of 45-50.4 Gy/25-28 fractions.
      Eleven of these patients also received concurrent and adjuvant 5-fluorouracil (5
      FU). Disease-free survival and overall survival were computed from the day of
      surgery using the Kaplan-Meier method. RESULTS: Seventy-six per cent (65/86) of
      patients had squamous cell carcinoma and 69% (59/86) of patients had tumours in
      the lower-third of the oesophagus. The median interval between surgery and PORT
      was 41 days, and 93% of patients received doses as planned. Strictures at the
      anastomotic site and ulcerations in the stomach mucosa were seen in 17% and 5% of
      patients, respectively. The median and 5-year disease-free survival was 12 months
      (95% CI 9.9-14.1) and 14%; whereas the median and 5-year overall survival was 17
      months (95% CI 12.4-21.6) and 17%, respectively. Local and distant failures were
      seen in 29% and 45% of patients, respectively. CONCLUSIONS: PORT, after a non
      curative resection of cancer oesophagus, is well tolerated with acceptable
      morbidity and survival.

PMID- 16097567
TI  - Metastatic solid-pseudopapillary tumour of the pancreas: clinico-biological
      correlates and management.
AB  - Solid-pseudopapillary tumour of the pancreas is a rare neoplasm of young women,
      currently categorised in the World Health Organization classification under
      exocrine pancreatic tumours. Increased awareness of this condition correlated
      recently with an apparent rise in incidence as well as recognition of more
      aggressive clinical courses. We describe two patients with solid-pseudopapillary
      tumour of the pancreas. A smaller, localised tumour in an unusually young white
      man was surgically excised with no evidence of recurrence after 2 years. The
      other case also had an uncommon presentation, with an aggressive course resulting
      in vascular encasement of the superior mesenteric bundle and aorta, and local
      involvement of the mesenteric lymph nodes. A literature review was carried out,
      and the main clinico-pathological features and strategies of treatment of solid
      pseudopapillary tumour of the pancreas are presented. Pathological, genetic and
      molecular features distinguish solid-pseudopapillary tumours from pancreatic
      ductal adenocarcinoma. Furthermore, neuroendocrine differentiation can be found
      focally in occasional cases of solid-pseudopapillary tumour. Patients with
      localised disease are usually cured by surgery. Prolonged survival can be seen in
      the presence of distant metastasis, if such lesions are resected surgically.
      Chemotherapy and radiation therapy are used in rare cases when resection is not
      possible. No current chemotherapy regimens are considered standard in the
      treatment of this tumour. A rational chemotherapy protocol for such a rare tumour
      needs to consider its origin and clinical behaviour. However, the indolent
      clinical progression of solid-pseudopapillary tumours is similar to that of
      pancreatic neuroendocrine tumour.

PMID- 16097568
TI  - ACT II: the second UK phase III anal cancer trial.

PMID- 16097569
TI  - Pre-operative plasma levels of vascular endothelial growth factor A, C and D in
      patients with colorectal cancer.
AB  - AIMS: Vascular endothelial growth factor (VEGF)-C and VEGF-D are angiogenic and
      lymphangiogenic members of the VEGF family of growth factors. Increased VEGF-C or
      VEGF-D expression in human tumours may be associated with lymph-node metastasis
      and lymphatic invasion. Circulating plasma levels of VEGF-A, VEGF-C and VEGF-D
      were measured in patients with colorectal cancer, and assessed for their
      usefulness as a diagnostic tool for determining lymph-node metastasis. MATERIALS
      AND METHODS: One hundred and twenty patients with colorectal cancer and 50
      healthy control patients were included in the study. Plasma growth-factor levels
      were assessed by enzyme-linked immunosorbent assays. RESULTS: No significant
      differences in plasma VEGF-C or VEGF-D levels were seen between patients
      subgrouped by clinicopathological variables. In particular, there were no
      differences in median plasma VEGF-C or VEGF-D level in patients with and without
      lymph-node involvement (VEGF-C: 11.2 U/ml [range, 4.9-51.9] vs 9.9 U/ml [4.4-93.4
      U/ml]; P = 0.90; VEGF-D: 335 pg/ml [113-1102] vs 316.5 pg/ml [0-1343]; P = 0.68).
      CONCLUSIONS: Circulating plasma levels of VEGF-C and VEGF-D do not allow pre
      operative identification of lymph-node status in patients with colorectal cancer.

PMID- 16097570
TI  - Treatment and survival from colorectal cancer: the experience of patients at
      South Australian teaching hospitals between 1980 and 2002.
AB  - AIMS: To evaluate trends in colorectal cancer survival and treatment at South
      Australian teaching hospitals and degree of adherence to treatment guidelines
      which recommend adjuvant chemotherapy for Dukes' C colon cancers and combined
      chemotherapy and radiotherapy for high-risk rectal cancers. MATERIALS AND
      METHODS: Trends in disease specific survival and primary treatment were analysed,
      and comparisons drawn between diagnostic epochs, using cancer registry data from
      South Australian teaching hospitals. Statistical methods included univariate and
      multivariable disease specific survival analyses. RESULTS: Five-year survival
      increased from 48% in 1980-1986 to 56% in 1995-2002. Largest gains were for stage
      C, where survivals were higher when chemotherapy was part of the primary
      treatment. By comparison, gains in 1-year survival were largest for stage D.
      Chemotherapy was provided for 4% of patients with colorectal cancers in 1980
      1986, increasing to 32% in 1995-2002. Among stage C cases below 70 years at
      diagnosis, the proportion having chemotherapy increased to 83% in 1995-2002. The
      most common chemotherapy was fluorouracil (5FU) as a single agent in 1980-1986
      and 5FU with leucovorin in 1995-2002. As expected, radiotherapy was used more
      frequently for rectal than colon cancers, and particularly for stage C. Among
      stage C rectal cases below 70 years, the proportion having radiotherapy increased
      from 10% in 1980-1986 to 57% in 1995-2002. Approximately 93% of colorectal
      cancers were treated surgically. Patients not treated surgically tended to be
      aged 80 years or more and to present with distant metastases. CONCLUSIONS: Trends
      in chemotherapy and radiotherapy accord with evidence-based recommendations.
      There have been reassuring gains in survivals after adjusting for stage, grade
      and other prognostic indicators. The data show survival gains and treatment
      patterns that individual hospitals can use as benchmarks when evaluating their
      own experience.

PMID- 16097571
TI  - Do serum levels of eosinophil granule-derived protein change in patients
      undergoing pelvic radiotherapy?
AB  - AIMS: Eosinophils have an important role in the pathogenesis of inflammatory
      bowel disease, with faecal levels of the eosinophil granule proteins, eosinophil
      cationic protein (ECP) and eosinophil protein X (EPX) reflecting disease
      activity. Eosinophil crypt abscesses are a characteristic histological finding in
      acute gastrointestinal radiation-induced mucosal damage. This pilot study aimed
      to investigate changes in serum levels of ECP/EPX during pelvic radiotherapy.
      MATERIALS AND METHODS: Patients with no history of inflammatory bowel disease,
      starting a 5-week course of pelvic radiotherapy, had serum ECP/EPX levels
      measured before radiotherapy and during the fourth week of treatment. Bowel
      toxicity was graded at week 4 using the Common Toxicity Criteria Scale. RESULTS:
      Fifteen patients who were to undergo adjuvant radiotherapy for gynaecological
      cancer were recruited. The mean serum levels of ECP and EPX before treatment were
      17.3 microg/l (range 2.0-49.3 microg/l) and 37.3 microg/l (range 12.0-94.0
      microg/l), respectively. The mean serum levels during week 4 of radiotherapy for
      ECP and EPX were 43.0 microg/l (range 2.4-164.0 microg/l) and 38.7 microg/l
      (range 9.0-79.0 microg/l), respectively. Serum ECP levels increased at week 4
      compared with levels before radiotherapy (P = 0.02). Acute bowel toxicity was
      seen in 12 patients (80%) at week 4: Grade 1 in 25% patients and Grade 2 in 75%.
      In this small study, no correlation was seen between acute bowel toxicity at week
      4 and serum ECP or EPX levels. CONCLUSIONS: Serum ECP levels increase in response
      to pelvic irradiation. This may reflect the known involvement of eosinophils in
      the acute response to radiotherapy. Further study is required to determine when
      levels start to rise and their relationship to the degree of acute bowel
      toxicity.

PMID- 16097572
TI  - Fatal radiation myelopathy after high-dose busulfan and melphalan chemotherapy
      and radiotherapy for Ewing's sarcoma: a review of the literature and implications
      for practice.
AB  - Radiation myelopathy is a rare, devastating, late effect of radiotherapy to the
      spinal cord. Spinal cord tolerance is currently accepted as about 50 Gy in 1.8-2
      Gy fractions. However, the effect of chemotherapy on cord tolerance is unclear.
      This issue is important, given the increasing use of chemotherapy in combination
      with radiotherapy. We describe the case of a 17-year-old boy with a right apical
      paraspinal Ewing's tumour in the neck treated with induction chemotherapy, high
      dose chemotherapy (busulfan and melphalan) with peripheral stem-cell rescue and,
      4 months later, radiotherapy to the primary tumour site (cervical cord received
      50 Gy in 30 fractions). After a latent period of 4 months, he developed a
      progressive, severe and ultimately fatal radiation myelopathy, which we suggest
      was due to a synergistic interaction between the high-dose chemotherapy and the
      radiotherapy. The use of such chemotherapy regimens in Ewing's tumours should be
      carefully considered, particularly when radiotherapy encompassing the spinal cord
      is an essential component of management.

PMID- 16097573
TI  - Unilateral multiple primary tumours in an atomic-bomb survivor.
AB  - We report here a case of an atomic-bomb survivor with sequential, unilateral,
      multiple-organ primary tumours after exposure to direct external radiation. This
      67-year-old woman was 8 years old when she was exposed to radiation from the
      atomic bomb. At the time of the explosion, she was in an open area, but hiding
      behind a tree, which shielded her left side. Therefore, the right side of her
      body was exposed to radiation directly and primarily. Since then, she has been
      diagnosed sequentially with breast cancer, ovarian tumour, thyroid tumour, head
      skin cancer and lung cancer. In each case, the tumour was on the right side of
      her body at the ages of 31, 38, 54, 58 and 64 years old, respectively. This case
      study indicates that the risk of multiple primary tumours should be considered in
      older atomic-bomb survivors.

PMID- 16097574
TI  - Cowden syndrome: a rare, but recognisable cancer predisposition disorder.

PMID- 16097575
TI  - Failure of a cetuximab/bevacizumab schedule in a patient with metastatic
      desmoplastic small round-cell tumour refractory to chemotherapy.

PMID- 16097576
TI  - Radiolabelled octreotide scintigraphy in patients with lymphoma--does it have a
      role in receptor-mediated radiotherapy?

PMID- 16097577
TI  - Recurrent arterial embolization from a metastatic carcinoma of unknown primary
      site.

PMID- 16097578
TI  - [Progress and variation of hematopoietic stem cell transplantation].

PMID- 16097579
TI  - [Present status in hematopoietic stem cell transplantation: bone marrow bank and
      non-relative bone marrow transplantation].

PMID- 16097580
TI  - [Present status in hematopoietic stem cell transplantation: peripheral blood stem
      cell transplantation].

PMID- 16097581
TI  - [Present status in hematopoietic stem cell transplantation: cord-blood
      transplantation].

PMID- 16097582
TI  - [Present status in hematopoietic stem cell transplantation: mini
      transplantation].

PMID- 16097583
TI  - [Treatment outcome of hematopoietic stem cell transplantation for acute
      leukemia].

PMID- 16097584
TI  - [Treatment outcome of hematopoietic stem cell transplantation for chronic
      myelogenous leukemia].

PMID- 16097585
TI  - [Treatment outcome of hematopoietic stem cell transplantation for aplastic
      anemia].

PMID- 16097586
TI  - [Treatment outcome of hematopoietic stem cell transplantation for myelodysplastic
      syndrome].

PMID- 16097587
TI  - [Treatment outcome of hematopoietic stem cell transplantation for malignant
      lymphoma].

PMID- 16097588
TI  - [Treatment outcome of hematopoietic stem cell transplantation for multiple
      myeloma].

PMID- 16097589
TI  - [Complications of hematopoietic stem cell transplantation and the treatment:
      graft-versus-host disease].

PMID- 16097590
TI  - [Complications of hematopoietic stem cell transplantation and the treatment:
      infections].

PMID- 16097591
TI  - [Graft-versus-leukemia as an allogeneic immune reaction].

PMID- 16097592
TI  - [Preventive measures for graft-versus-host disease].

PMID- 16097593
TI  - [Feto-maternal immune tolerance and hematopoietic stem cell transplantation].

PMID- 16097594
TI  - [Present status in hematopoietic stem cell transplantation (discussion)].

PMID- 16097595
TI  - [Rhabdomyolysis: case report of 11 patients].

PMID- 16097596
TI  - [Cardiac sarcoidosis detected by FDG-PET].

PMID- 16097597
TI  - [Primary pulmonary Hodgkin's disease].

PMID- 16097598
TI  - [Successful treatment of MPO-ANCA associated glomerulonephritis with high dose
      intravenous immunoglobulin].

PMID- 16097599
TI  - [Nonsystemic vasculitic neuropathy treated with steroid and azathioprine].

PMID- 16097600
TI  - [Clinical studies on multiple system atrophy].

PMID- 16097601
TI  - [Pulmonary fibrosis and apoptosis].

PMID- 16097602
TI  - [Present status and future prospects in reduced intensity stem cell
      transplantation].

PMID- 16097603
TI  - [Roll of aldosterone in pathogenesis of kidney disorders].

PMID- 16097604
TI  - [Recent progress in study of dendritic cells in liver diseases].

PMID- 16097605
TI  - [Anesthesia for thoracic surgery in elderly patients].
AB  - Aging and advances in medical technology have lead to a rise in the number of
      patients of advanced age undergoing surgery. This is also observed in thoracic
      surgery. Aging itself is not a disease, but it is one of the risk factors of
      perioperative complications. Individual assessment of patients is required to
      ascertain the organ system capacity and functional reserve. The management of
      anesthesia is based on the characteristic changes in the elderly, related to
      physiology and pharmacokinetics, taking account of possible perioperative
      complications.

PMID- 16097606
TI  - [Perioperative care for thoracic surgery with complications in elderly patients].
AB  - Perioperative care for high-aged coronary artery bypass grafting (CABG), thoracic
      aortic aneurysm and lung cancer is discussed. Among them, each disease has their
      characteristics and complications. Especially, respiratory, cerebral and
      cardiovascular complications are common in high-aged patients requiring thoracic
      surgeries. Careful management is mandatory during these surgeries.

PMID- 16097607
TI  - [Cardiac rehabilitation after cardiovascular surgery in elderly patients].
AB  - We assessed whether cardiac rehabilitation after acquired cardiovascular surgery
      in octogenarians was helpful to return daily life or not. Among overall 3,050
      patients in these 10 years, 130 patients (4.3%) aged 80 years or older underwent
      cardiovascular surgery in our institute. Cardiac rehabilitation program in
      hospital was achieved in 118 octogenarians after surgery. Physical and
      phychological activity had improved by means of this program. Notably,
      observational rehabilitation on monitor and examination of anaerobic threshold
      (AT) point were of great importance to evaluate the efficacy of cardiac
      rehabilitation. Thereby, hospital stay after surgery was longer than usual, mean
      hospital stay was 32.1 +/- 5.1 days. Future perspectives of cardiac
      rehabilitation in an outpatient would be expected.

PMID- 16097608
TI  - [Respiratory rehabilitation in elderly patients after surgical treatment in the
      thoracic region].
AB  - Respiratory rehabilitation is performed by a team of physicians, nurses,
      physiotherapists (respiratory therapists), nutritionists, and pharmacists
      together with the patient's family if necessary. In elderly patients, in whom
      chronic obstructive pulmonary disease (COPD) is often complicated before and
      after surgery, it is necessary to start respiratory physiotherapy and
      kinesiotherapy as the major therapies of respiratory rehabilitation in the early
      stage after surgery. Postoperative control of the amount of sputum, and recovery
      and maintenance of ventilatory gas exchange become possible by early respiratory
      rehabilitation, leading to prevention of complications, recovery of activities of
      daily living (ADL), and early discharge from hospital.

PMID- 16097609
TI  - [Influences of cardiopulmonary bypass in elderly patients].
AB  - Organ hypofunction by aging exaggerate damages, which are caused by
      cardiopulmonary bypass. The main cause of organ dysfunction after cardiopulmonary
      bypass is systemic inflammatory response, which is induced by continuous
      interaction of blood with unphysiologic surfaces, shear stress to blood cells,
      and incorporation of abnormal substances. To reduce the postoperative
      complications after cardiovascular surgery in elderly patients, intensive and
      careful control of cardiopulmonary bypass and several kinds of anti-inflammatory
      treatment are important.

PMID- 16097610
TI  - [Indication and strategy of on-pump coronary artery bypass grafting in elderly
      patients].
AB  - As elderly people are increasing nowadays, so is coronary artery bypass grafting
      (CABG) for these older patients. The risk of on-pump CABG for elderly patients is
      thought to be higher than that for younger patients. We assessed 12 patients, 80
      years of age or older, who underwent on-pump CABG, and compared them with 1,988
      patients younger than 80 years old. In the elderly patient group, there were no
      in-hospital mortality and no postoperative complications. There was no
      statistical difference in the pre- and postoperative factors between the 2 groups
      except for the cardiopulmonary bypass time. We also compared the pre- and
      postoperative factors of 341 patients, 70 years of age or older, who underwent on
      pump CABG with those of 1,659 patients under 70 years of age. The preoperative
      factors of elderly patients indicated that they were more severely ill than
      younger patients. In the analysis of postoperative factors, the rate of
      postoperative complications were similar between the 2 groups, despite the
      significantly higher rate of in-hospital mortality in the elderly group. The risk
      of on-pump CABG for elderly patients is higher than that for younger patients,
      but with careful management of the pre-, intra-, and postoperative procedures, we
      can perform on-pump CABG safely even in the elderly patients.

PMID- 16097611
TI  - [Performing off-pump coronary artery bypass grafting in elderly patients safely].
AB  - The elderly patients of the ischemic heart disease have been increasing in recent
      years. From January 2001 to December 2004, 41 patients were aged 80 years or
      older underwent off-pump coronary artery bypass grafting (OPCAB) in our hospital.
      To perform OPCAB of elderly patient safely, we review presence of carotid artery
      stenosis and previous cerebral infarction preoperatively and use high thoracic
      epidural anesthesia (TEA) and coronary artery active perfusion system (CAPS)
      intraoperatively. TEA provides bradycardia and coronary vasodilatation which
      facilitate beating-heart surgery technically, and prevent intra- and
      postoperative arrhythmia. Comparing with before use of TEA, operating time and
      postoperative intubation time decreased significantly. Using CAPS anastomosis was
      performed under bloodless field and stable hemodynamics. There was no operative
      death and severe postoperative complication. In conclusion, with careful
      preoperative inspection and using TEA and CAPS, OPCAB can be performed safely in
      octogenarians.

PMID- 16097612
TI  - [Graft selection in elderly patients undergoing isolated coronary artery
      revascularization].
AB  - Several studies have shown that off-pump coronary artery bypass (OPCAB) in
      elderly patients is better in terms of postoperative complications and length of
      hospital stay. We evaluated the outcomes of isolated OPCAB in octogenarians. From
      June 2002 to December 2004, 26 patients underwent isolated coronary artery bypass
      grafting (CABG). All patients underwent OPCAB. These included 4 emergency cases
      and 12 in an urgent situation, so the overall non-elective rate was 61.5%. There
      was no hospital death or serious complication. The mean number of grafts per
      patient was 3.2 +/- 1.6, and the complete revascularization rate was 90.4%. All
      patients received at least 1 arterial conduit, and 16 patients (61.5%) received
      all arterial grafts. Saphenous vein grafts were used in 10 patients. These values
      were not significantly different from those in patients in their 70s who
      underwent CABG during the same period. We conclude that even in high-risk
      octogenarian patients, with the aid of the off-pump technique, we can safely
      perform complete revascularization using more arterial conduits with minimal
      risk.

PMID- 16097613
TI  - [Mechanical complications of myocardial infarction in elderly patients].
AB  - As mechanical complications after myocardial infarction in the elderly, we
      described the therapeutic strategies for postinfarction ventricular septal
      perforation (PVSP), ischemic cardiomyopathy (ICM), and ischemic mitral
      regurgitation (IMR). To improve operative results for PVSP in the elderly, it is
      important to maintain hemodynamics by cardiac support device such as intraaortic
      balloon pumping, and to perform prompt surgical intervention before cardiogenic
      shock and multiple organ failure. Infarct exclusion technique is a standard
      surgery for PVSP. Both ICM and IMR are common disease caused by severe cardiac
      ischemia and mitral valve (MV) function is related to left ventricular (LV)
      geometry. We consider total MV-LV geometrical repair by LV restoration surgery,
      MV repair, and coronary revascularization is essential to improve morphological
      abnormality in LV and MV even in the elderly. To maximize LV function, septal
      anterior ventricular exclusion (SAVE) technique for antero-septal myocardial
      ischemia, apex-sparing Batista operation for lateral ischemia, and undersized
      mitral annuluoplasty to improve LV sphericity are procedures of choice. However,
      it is still difficult to save elderly patients with very low cardiac function.
      Novel treatments such as regenerative medicine by angiogenic cytokines and/or
      cell transplantation, and advanced medical treatments are waited for this high
      risk group.

PMID- 16097614
TI  - [Surgical strategies for aortic valve disease in elderly patients].
AB  - Population of elderly people is increasing and aortic valve disease due to
      degeneration with aging process, especially aortic stenosis (AS) is increasing in
      elderly patients. With development and great use of non-invasive diagnostic
      techniques, particularly echocardiography, the diagnosis and evaluation of aortic
      valve disease are even safer in these patients. Aortic valve replacement (AVR) is
      effective treatment for symptomatic AS, however, generally has a higher risk in
      elderly patients, especially 80 years and over patients. Several reports
      demonstrated acceptable operative mortality and morbidity in elderly patients. We
      performed AVR or AVR with other cardiac surgical procedures in 16 cases of 80
      years and over patients from 1998 to 2004, and there were no operative or
      hospital death. Therefore, AVR in 80 years and over patients could be acceptable
      surgical treatment and age alone is not contraindication.

PMID- 16097615
TI  - [Mitral valve disease in elderly patients].
AB  - It seems that mitral valve surgery in patients older than 80 years increase
      against the background of the aging society. Basically, there are not particular
      differences between elderly patients and younger patients in procedures for
      diagnosis and operative indication in mitral valve diseases. However, cardiac
      surgery for patients older than 80 years has been reported to have high mortality
      rate. Therefore, it is necessary that we should evaluate and treat complications
      of important organs such as brain/coronary artery/lungs/liver/kidney, adequately.
      Our mortality rate of the whole mitral valve operations was 2.4% and that of
      patients older than 75 years was 7.9%. This result compares favorably with those
      reported from other institutions. However, when we perform mitral valve
      operations for patients older than 80 years, it is necessary to investigate
      activities of daily living and quality of life before and after the operation.

PMID- 16097616
TI  - [Minimal invasive cardiac surgery using port-access method in elderly patients].
AB  - Cardiac surgery in elderly patients are increasing in recent years. From October
      1997 to December 2004, we operated on 163 patients with port-access cardiac
      surgery, of whom 5 were over 70 years old (elderly group) and 158 were 16-69
      years old (young group). The patients were 91 with atrial septal defect (ASD), 64
      with mitral valve disease, 2 with coronary artery disease (coronary artery bypass
      grafting : CABG), and 10 with other (ventricular septal defect : VSD, myxoma et
      al.). This report presents result of port-access cardiac surgery in elderly
      patients. No significant difference was found between 2 groups in extracorporeal
      time, aortic clamp time, postoperative intubation period and postoperative
      hospital stay. However, the transfusion rate in mitral valve lesion were higher
      in elderly patient (100%) than in younger ones (18%). In conclusion, it seems
      that port-access cardiac surgery was to be a useful for elderly patient though
      contraindications were accepted such as peripheral arteriosclerosis and
      calcification of aorta.

PMID- 16097617
TI  - [Aortic dissection in elderly patients].
AB  - We performed 12 operations for aortic dissection in octogenarians from 1997 to
      2004. Male : female = 1 : 11. Mean duration of follow-up is 33 +/- 19 months. As
      regards the etiology, acute type A aortic dissection was 8, chronic type A aortic
      dissection was 3 and chronic type B aortic dissection with distal arch aneurysm
      was 1. Total arch replacement was performed in 2 patients and hemiarch
      replacement in 10. In all patients with acute type A aortic dissection, hemiarch
      replacement was performed with the aid of selective cerebral perfusion or deep
      hypothermic circulatory arrest with retrograde cerebral perfusion. Postoperative
      respiratory failure was found in 1 patient, re-exploration for bleeding in 1,
      mediastinitis in 1 and temporary neurological dysfunction in 1. There was no
      hospital mortality. Two patients were died of respiratory failure 4 and 27 months
      after surgery. The results were acceptable. We recommend that age should not be
      the only determinant in deciding whether emergency operation should be performed
      in octogenarians.

PMID- 16097618
TI  - [Surgery for aneurysms of the aortic arch in elderly patients].
AB  - Surgery for aneurysms of the aortic arch in octogenarians can be performed with
      increased but operative mortality remains high. Minimally invasive operation may
      be required for further improvement of the outcome of surgery for aneurysms of
      the aortic arch in octogenarians. Aged patients with life-threatening events have
      excessive mortality and morbidity. We think that sugery for aneurysms of the
      aortic arch in octogenarians should not be withheld on the basis of age alone,
      but should be based on careful assessments of the relative medical risks and
      benefits, as well as the wishes of the patients and family.

PMID- 16097619
TI  - [Endovascular stent grafting for thoracic aortic disease in elderly patients].
AB  - Despite advances in operative technique and management having improved the
      clinical outcomes of conventional open surgical replacement for thoracic aortic
      aneurysms, it remains an invasive procedure especially for aged patients. Over
      the past 10 years, minimally invasive endovascular surgery using a stent graft,
      has made significant advances for the treatment of aneurysms. For 10 years from
      1995, 476 patients of thoracic aortic aneurysms were treated with the
      endovascular technique using the stent graft in our hospital. Exclusion of the
      aneurysms without endoleak were achieved within 2 weeks postoperatively in over
      95%. Also in elderly patients (46/476), same good results came out. Endovascular
      stent grafting shows potential as a safe and useful treatment for thoracic aortic
      aneurysms, but further investigation should attempt to determine its efficacy
      over a longer postoperative period.

PMID- 16097620
TI  - [Aortic root reconstruction in elderly patients].
AB  - Operative indications for aortic root reconstruction generally include aortic
      root aneurysm, root destruction in acute dissection, extensive annular abscess in
      infective endocarditis, and small aortic annuls. In elderly patients, Bentall
      operation with bioprosthesis should be one of the standard operation because
      bioprosthesis in aortic position demonstrated excellent long-term valve
      durability. Freestyle aortic bioprosthesis has been increasingly implanted as a
      full root replacement in elderly patients with small aortic annuls and carcified
      aortic root. When aortic valve is nearly normal, valve-sparing aortic root
      replacement can be an ideal operation without need for prosthetic valve.
      Indication for valve-sparing operation should be considered when the patient is
      physically and socially active and does not carry significant comorbidity.

PMID- 16097621
TI  - [Thoracic trauma in elderly patients].
AB  - We investigated clinical character of thoracic trauma in the octogenarians in
      local city. Between Jan 2000 and Dec 2004, 369 patients with thoracic trauma were
      managed in our clinic and 3 local city hospitals in Oita. Ninety patients (23%)
      were aged 80 or above, 177 patients (46.7%), 64 or below, and 102 patients
      (26.9%), from 65 to 79. Blunt trauma occurred in the elderly. Penetrating trauma
      occurred in only 3 younger patients. In the octogenarians, causes of trauma were
      falls in 54 (60%) of the patients, traffic accidents in 15 (16.7%), and strained
      back in 14 (15.6%). Falls occurred on steps, most commonly, from flat surface as
      the elder fails to navigate environmental hazards or simply drops owing to a
      syncopal episode or loss of balance. Fractures of the thoracic vertebrae with or
      without rib fractures were observed in 29 (32.2%) of the octogenarians. Overall
      mortality was 2.3%. Three octogenarians (3.3%) died of pneumonia. Twenty-two
      (24.4%) of the octogenarians could discharge to their home, but the other 67
      patients (74.4%) were referred to nursing home. CONCLUSION: Falls most commonly
      occur in the octogenarians. Occasionally, the patients require to discharge to
      nursing home, because of fracture of thoracic vertebrae or debilitated disorder.

PMID- 16097622
TI  - [Pneumothorax in elderly patients].
AB  - Pneumothorax is a frequent affliction with the incidence peaks in youth and old
      age. The disease is more frequent in males and smokers. Most of the old patients
      have emphysema and/ or pulmonary fibrosis as the underlying disease. They often
      show low respiratory function and/ or heart failure. The first step in treatment
      is pleural drainage to achieve pulmonary re-expansion. If it is difficult to cure
      by pleural drainage, we try to perform pleurodesis using the chemicals such as OK
      432 and tetracycline. As the next step, we try to perform video assisted thoracic
      surgery (VATS) or operation without video. To stop smoking is important before
      and after operation. We reviewed about pneumothorax in old patients.

PMID- 16097623
TI  - [Lung volume reduction surgery for chronic pulmonary emphysema in elderly
      patients].
AB  - We have performed thoracoscopic lung volume reduction surgery (LVRS) for severe
      chronic pulmonary emphysema irrespective of the patient's age. Between May 1993
      and April 2004, 9 patients older than 75 years underwent LVRS at our hospital.
      Three of the 9 patients substantially improved lung function and quality of life
      after LVRS. One patient slightly improved them but went back to the preoperative
      condition 5 years after LVRS. The other 5 patients showed no clinical improvement
      after LVRS, 3 of the 5 developed CO2 narcosis and failed weaning from the
      respirator. Although patient's age older than 75 years is not contra-indication
      for LVRS, careful selection is needed for LVRS in elderly patients.

PMID- 16097624
TI  - [Bacterial infections of the lung in the elderly].
AB  - Many cases of the lung abscess of the elderly ages are the outcome of aspiration
      pneumonia attributable to miss-swallowing. These cases basically have the risky
      conditions of repeated miss-swallowing such as cerebrovascular diseases,
      regurgitation from stomach to esophagus and so on. Even if the infected lung
      tissues were resected completely, habitual miss-swallowing can produce the
      aspiration pneumonia or lung abscess again. Non-surgical therapy is superior for
      the lung abscess caused by miss-swallowing. The group of the lung abscess due to
      lung cancer requires the surgery because other treatments can not cure the severe
      inflammation. This surgery aims primarily the recovery from infected condition of
      the lung, and sometimes the curative resection is impossible. The prognosis of
      the group is not always good. The lung abscess often accompanies severe adhesion
      to the thoracic wall due to inflammation, consequently the surgeons are obliged
      to stressful surgery with bleeding and a long time.

PMID- 16097625
TI  - [Pleural empyema in elderly patients].
AB  - We shall consider carefully for surgical management of pleural empyema in elderly
      patients over 80 years old for the reason that their preoperative conditions are
      frequently poor, due to such as several complications, low activity of dayly life
      and immunodeficiency on account of undernutrition. Sufficiently drainage and
      cleaning the abscess cavity by irrigation of saline with antibiotics through
      chest tube are required in acute period of empyema. In chronic period of empyema,
      prolonged hospitalization because of unsucusessful drainage, surgical management
      is necessary. Various surgical procedures reported by many authors were reviewd
      and suitable method should be selected respectively, taking individual states of
      elderly patients into consideration.

PMID- 16097626
TI  - [Pulmonary tuberculosis in elderly patients].
AB  - Since the introduction of rifampicin, it has been believed that pulmonary
      tuberculosis can be cured with medication alone. However, if tubercle bacilli are
      resistant to isoniazid and rifampicin, the success rate of medical treatment
      falls considerably. These bacilli are defined as multidrug-resistant tuberculosis
      (MDR-TB) and have been of great concern. To improve the outcome of chemotherapy
      in patients with MDR-TB, adjuvant resectional surgery has been advocated.
      Currently the most common indication for pulmonary resection in patients with
      tuberculosis is MDR-TB. Pulmonary resection for MDR-TB achieves a high cure rate
      with low morbidity and mortality. The majority of the MDR-TB patients in the
      previously reported surgical series were middle-aged, and pulmonary resection for
      MDR-TB has not been performed on the octogenarians. The oldest patient in our
      series was 65 years old. Nevertheless, pulmonary resection is worth considering
      for an octogenarian infected with MRD-TB because pulmonary resection achieves a
      high success rate with low morbidity and mortality.

PMID- 16097627
TI  - [Lung cancer in elderly patients: lung cancer and lung function].
AB  - The incidence of bronchogenic carcinoma is increasing as life expectancy rises.
      With increase in the aged population in Japan, the number of patients suffering
      from lung cancer and candidates for lung resections are increasing. In this
      paper, the author lists up indispensable procedures for diagnosis, namely, lung
      function tests, unilateral pulmonary arterial occlusion test and exercise
      tolerance test. The cut-offs for identifying candidates for elderly patients for
      lung resections can be applied the same cut-offs for younger patients. Also the
      author indicates the importance of postoperative management for lung lobe
      resections. In order to prevent postoperative problems such as congestive heart
      failure that might be a fetal complication, the most useful check values after
      the lung surgery for elderly patients are rate of transfusion and urine volume.
      In conclusion, when elderly patients assert their rights to undergo lung surgery,
      we, the thoracic surgeons, should reply their requests under the equal quality of
      safe surgery as that for younger patients. Besides, it is desirable that even
      elderly patients, over 80 years old, who undergo lung surgery should guarantee
      their quality of daily life after surgery.

PMID- 16097628
TI  - [Lung cancer in elderly patients: clinicopathological features].
AB  - The clinicopathological features of lung cancer in octogenarian in Japan,
      including of our experienced cases, were discussed, in particular, on the
      surgical treatment, prognosis and postoperative complications. Due to the
      expanding of life span of Japanese elder people, the surgical indications for the
      patient with lung cancer over 80 years old have been extended today, and its
      prognosis seem to be almost similar as the another generations under 80. From
      now, the surgical option will be adopted more and more for the patient of stage I
      and II of lung cancer with good performance status.

PMID- 16097629
TI  - [Thymoma in elderly patients].
AB  - One hundred and twenty-three cases with primary thymoma have undergone an
      operation from 1972. Sixteen elderly patients (over 70 years old) were compared
      with 107 young patients in clinical appearance, pathological findings and
      outcome. There were no differences in Masaoka's classification, World Health
      Organization (WHO) pathological classification and frequency of complications as
      myasthenia gravis in both groups. In elderly patients different kinds of
      neoplasms often occurred during follow-up periods compared to in young patients.
      In both groups, basically policy of treatment is same. In the case of stage I or
      II, (extended) thymothymomectomy is performed. In the case of stage IIl, partial
      resection of invaded surrounding organs is added. We often perform preoperative
      corticosteroid therapy to shrink the tumor. In the case of stage IV a with
      pleural dissemination, thymothymomectomy with resection of all dissemination
      lesions is performed. The case with widespread invasion to pericardium and
      pericardial dissemination are considered as inoperable and undergo
      chemoradiotherapy. Postoperatively radiotherapy is added in the case of stage III
      and IV. In elderly patients 5 and 10 year survival rates were 60.2 and 48.1%.
      These were significantly worse compared to young patients. It depended on
      postoperative complications as sternomyelitis and different kinds of critical
      complications.

PMID- 16097631
TI  - [Thoracoscopic surgery for elderly patients].
AB  - To clarify the feasibility of lung resections, especially those with video
      assisted thoracoscopic surgery (VATS), for elderly patients with primary non
      small cell lung cancer, 14 patients aged 80 to 83 years who had undergone
      surgical treatment at Tohoku University Hospital from 1997 to 2004 were
      retrospectively reviewed. Thirteen of 14 patients had clinical stage I lung
      cancer and VATS lobectomy was applied to 7 of 9 patients undergoing VATS. One
      hospital death with acute exacerbation of interstitial pneumonia was recorded in
      a patient undergoing standard thoracotomy because of severe pleural adhesion.
      Overall 5-year survival rates of these 13 patients were 63.3% and those with VATS
      lobectomy were 66.7%. We conclude that VATS lobectomy is a feasible therapeutic
      option to be offered to selected elderly patients with clinical stage I lung
      cancer.

PMID- 16097630
TI  - [Surgical therapy for elderly patients with mediastinal neoplasms except for
      thymic epithelial tumors].
AB  - Surgical treatment for old patients with mediastinal neoplasms except for those
      of thymic epithelial origin was retrospectively reviewed. Ten (7.5%) out of 133
      patients who had underwent surgical therapy for extrathymic mediastinal tumors in
      our institute were no younger than 70. Two of them had malignant neoplasms (a
      germ cell tumor and a malignant fibrous histiocytoma). One (0.75%) 76-year-old
      patient with a thymic cyst had died of the pulmonary thromboembolism on the 3rd
      postoperative day. A 76-year-old patient with a malignant germ cell tumor had
      undergone reexploration because of persistent air leakage from the bronchopleural
      fistula. Surgical procedures were practically performed to determine the
      pathological diagnosis or to treat the patients with pathologically benign
      neoplasms because of diverse biological behaviors of these mediastinal tumors. In
      conclusion, surgical indications of the extrathymic mediastinal neoplasms should
      be more strictly limited and less invasive surgery should be applied to older
      patients as far as possible.

PMID- 16097632
TI  - [Surgery for cancer of the esophagus in elderly patients].
AB  - Esophageal cancer has a fulminant biological characteristic, and shows a higher
      rate of lymph node metastasis than other gastrointestinal malignancies. The
      distribution of lymphatic spread is wide from cervical to abdominal field, and 3
      field lymph node dissection is a standard procedure in esophageal cancer surgery.
      However, the morbidity and mortality rate following esophageal resection is
      higher than that of other gastrointestinal or thoracic surgery. The most serious
      postoperative complication of esophageal surgery in elderly patients is a
      pulmonary problem. In order to reduce postoperative pulmonary complications, we
      try to preserve bronchial artery, pulmonary branches of the vagal nerve, in
      addition to definite preservation of bilateral recurrent laryngeal nerve. Our
      survival rate and mean survival period in elderly patients with esophageal cancer
      was fairly good. To achieve a high survival rate and reduce postoperative
      morbidity and mortality in elderly patients, preoperative assessment of pulmonary
      function and quality control of surgical procedure is essential.

PMID- 16097633
TI  - Effects of tissue heterogeneity on cerebral vascular response to acetazolamide
      stress measured by an I-123-IMP autoradiographic method with single-photon
      emission computed tomography.
AB  - OBJECTIVES: Single-photon emission computed tomography (SPECT) with iodine-123
      (123I)-labeled N-isopropyl-p-iodoamphetamine (IMP) is widely used in measuring
      the cerebral blood flow (CBF) response to acetazolamide stress for assessment of
      cerebral vascular reserve. To quantitate CBF by means of SPECT with IMP, an
      autoradiographic (ARG) method has been developed and is widely used. Because the
      relation between the brain counts on the SPECT scan and CBF is not linear in the
      ARG method, a mixture of gray and white matter in a pixel causes errors in the
      calculation of CBF. In the present study, errors in the calculation of CBF and
      vascular response to acetazolamide stress by the ARG method due to tissue
      heterogeneity were estimated by simulation study. Correction for effects of
      tissue heterogeneity in SPECT data was also attempted. METHODS: Images of gray
      and white matter fraction were obtained by voxel-based morphometry analysis of
      magnetic resonance (MR) imaging data set. Ideal CBF images, which were generated
      from gray and white matter fraction images with assumed blood flow values for
      gray and white matter, were compared to CBF images generated by the ARG method.
      Correction for effects of tissue heterogeneity in SPECT data was performed with
      gray and white matter fraction data obtained from MR images. RESULTS: Systematic
      underestimation of CBF due to tissue heterogeneity was observed in all brain
      regions. In the neocortical regions, underestimation by -21% to -16%, -26% to 
      20%, -31% to -24%, and -35% to -27% was observed for gray and white matter blood
      flow of 80 and 20, 100 and 25, 120 and 30, and 140 and 35 ml/100 ml/min,
      respectively. Vascular response was also systematically underestimated in most
      brain regions. Vascular responses in the neocortical regions ranged from 17% to
      20%, from 31% to 37%, and from 42% to 52% when ideal vascular responses were 25%,
      50%, and 75%, respectively. After correction for the effects of tissue
      heterogeneity, values of vascular response to acetazolamide stress ranged from
      64% to 116% in the neocortical regions, whereas values obtained by the ARG method
      ranged from 48% to 52%. CONCLUSION: Underestimation of the vascular response to
      acetazolamide stress due to tissue heterogeneity should be considered in the
      estimation of cerebral vascular reserve.

PMID- 16097634
TI  - Imaging of lesions in a murine rheumatoid arthritis model with a humanized anti
      interleukin-6 receptor antibody.
AB  - Rheumatoid arthritis (RA) has been attributed to the abnormal production of
      cytokine interleukin-6 (IL-6), which has a variety of physiological activities.
      In vivo IL-6-receptor imaging provides useful suggestions regarding the mechanism
      of anti-IL-6-receptor antibody action and indicates a basic therapeutic strategy
      for treating RA. Therefore, this study was designed to establish a method for
      radiolabeling anti-IL-6-receptor antibodies and to investigate the feasibility of
      using radiolabeled anti-IL-6-receptor antibodies in the scintigraphic imaging of
      lesions in an animal RA model. Anti-IL-6-receptor antibodies were conjugated with
      a bifunctional chelating agent, hydrazinonicotinamide (HYNIC), and radiolabeled
      with technetium-99m (99mTc) using the ligand exchange reaction of 99mTc-tricine
      complex. The binding affinity was estimated using the U266 cell line. Whole body
      scintigraphy, biodistribution and autoradiography were undertaken in mice
      containing synovial cells that had been transplanted from an RA patient. Our
      findings showed that the antibodies accumulated in the implanted tissue. When
      radiolabeled anti-IL-6-receptor antibodies are used in scintigraphic imaging, the
      distribution of the IL-6-receptors is associated with the inflammatory cell
      infiltration that is seen in the early stage of RA. Accordingly, imaging with
      humanized anti-IL-6-receptor antibodies appears to be useful for detecting early
      pathophysiological conditions and assessing the efficacy of antibody treatment as
      well as the prognosis of patients with RA.

PMID- 16097635
TI  - PET evaluation of the relationship between D2 receptor binding and glucose
      metabolism in patients with parkinsonism.
AB  - OBJECTIVE: To clarify the relationship between D2 receptor binding and the
      cerebral metabolic rate for glucose (CMRGlu) in patients with parkinsonism, we
      simultaneously measured both of these factors, and then compared the results.
      METHODS: The subjects consisted of 24 patients: 9 with Parkinson's disease (PD),
      3 with Juvenile Parkinson's disease (JPD), 9 with multiple system atrophy (MSA),
      and 3 with progressive supranuclear palsy (PSP). The striatal D2 receptor binding
      was measured by the C-11 raclopride transient equilibrium method. CMRGlu was
      investigated by the F-18 fluorodeoxyglucose autoradiographic method. RESULTS: The
      D2 receptor binding in both the caudate nucleus and putamen showed a positive
      correlation with the CMRGlu in the PD-JPD group, but the two parameters
      demonstrated no correlation in the MSA-PSP group. The left/right (L/R) ratio of
      D2 receptor binding in the putamen showed a positive correlation with that of
      CMRGlu in the MSA-PSP group, while the two demonsrated no correlation in the PD
      JPD group. CONCLUSION: Our PET study showed striatal D2 receptor binding and the
      CMRGlu to be closely related in patients with parkinsonism, even though the
      results obtained using the L/R ratios tended to differ substantially from those
      obtained using absolute values. The reason for this difference is not clear, but
      this finding may reflect the pathophysiology of these disease entities.

PMID- 16097637
TI  - Apparent CBF decrease with normal aging due to partial volume effects: MR-based
      partial volume correction on CBF SPECT.
AB  - Several studies using single photon emission tomography (SPECT) have shown
      changes in cerebral blood flow (CBF) with age, which were associated with partial
      volume effects by some authors. Some studies have also demonstrated gender
      related differences in CBF. The present study aimed to examine age and gender
      effects on CBF SPECT images obtained using the 99mTc-ethyl cysteinate dimer and a
      SPECT scanner, before and after partial volume correction (PVC) using magnetic
      resonance (MR) imaging. Forty-four healthy subjects (29 males and 15 females; age
      range, 27-64 y; mean age, 50.0 +/- 9.8 y) participated. Each MR image was
      segmented to yield grey and white matter images and coregistered to a
      corresponding SPECT image, followed by convolution to approximate the SPECT
      spatial resolution. PVC-SPECT images were produced using the convoluted grey
      matter MR (GM-MR) and white matter MR images. The age and gender effects were
      assessed using SPM99. Decreases with age were detected in the anterolateral
      prefrontal cortex and in areas along the lateral sulcus and the lateral
      ventricle, bilaterally, in the GM-MR images and the SPECT images. In the PVC
      SPECT images, decreases in CBF in the lateral prefrontal cortex lost their
      statistical significance. Decreases in CBF with age found along the lateral
      sulcus and the lateral ventricle, on the other hand, remained statistically
      significant, but observation of the spatially normalized MR images suggests that
      these findings are associated with the dilatation of the lateral sulcus and
      lateral ventricle, which was not completely compensated for by the spatial
      normalization procedure. Our present study demonstrated that age effects on CBF
      in healthy subjects could reflect morphological differences with age in grey
      matter.

PMID- 16097636
TI  - Evaluation of breath-hold 201Tl SPECT in the differential diagnosis of solitary
      pulmonary nodules.
AB  - The aim of this study was to evaluate the usefulness of deep inspiration breath
      hold SPECT (BrST, a method for 201Tl SPECT) in the diagnosis of solitary
      pulmonary nodules (SPN). METHODS: Ten patients with malignant lesions and five
      with benign lesions were enrolled in this study. Early SPECT acquisition was
      performed 15 min after injection of 201Tl, while delayed SPECT images were
      acquired 3 h after injection. The first 15-sec acquisition was done using the
      BrST technique, and the second with the conventional free breathing (FB) method.
      We performed this technique alternately, and therefore, the odd data were from
      BrST and the even data were from FB. We referred to the T/N ratio of the early
      images as the ER and to the T/N ratio of the delayed images as the DR. To semi
      quantitatively evaluate the degree of retention in the lesion, the retention
      index (RI) was calculated. RESULTS: The RI of BrST indicated greater accuracy
      than that of FB in the differential diagnosis of SPN. For the benign and
      malignant lesions, the RI of BrST was -3.07 +/- 31.51 and 29.86 +/- 25.01,
      respectively (p < 0.05). The sensitivity, specificity, and accuracy of BrST (80%,
      80%, and 80%, respectively) were significantly higher than those of FB (p <
      0.05). CONCLUSION: The BrST method is more accurate than that of the conventional
      FB method in the differential diagnosis of SPN.

PMID- 16097638
TI  - Usefulness of gastroesophageal reflux scintigraphy using the knee-chest position
      for the diagnosis of gastroesophageal reflux disease.
AB  - OBJECTIVES: The aim of this study is to evaluate the usefulness of
      gastroesophageal reflux (GER) scintigraphy using the knee-chest (KC) position for
      the diagnosis of gastroesophageal reflux disease (GERD). METHODS: The study
      subjects were 37 patients with GERD and 8 healthy volunteers (control group).
      Endoscopically observed esophageal mucosal breaks were evaluated with the Los
      Angeles classification. For GER scintigraphy, the subjects ingested liquid yogurt
      labeled with 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) and water.
      Imaging was performed in the supine and KC position, and GER was graded as 1-4
      according to the extent of GER assessed by scintigraphy. RESULTS: GER
      scintigraphy revealed no reflux in the control group (specificity: 100%). In the
      supine position, gastroesophageal reflux was observed in 49% of the patients with
      GERD, compared to 76% in the KC position. 21 of 23 (91%) patients with erosive
      esophagitis were shown to have GER with scintigraphy. GER scintigraphy revealed
      severe reflux (grade 3 or 4) (83%, 10/12) in the patients who had severe mucosal
      breaks (LA grade C or D). GER scintigraphy detected grade 1 or 2 reflux in 7 of
      the 14 patients who were endoscopically negative. There was a correlation between
      the endoscopically determined severity of mucosa and the reflux grade which was
      determined with GER scintigraphy. CONCLUSION: GER scintigraphy can detect
      gastroesophageal reflux with a high sensitivity in the KC position and might be a
      useful method in the screening and assessment of the severity of this disease.
      This method would be useful for the diagnosis of GERD in endoscopically negative
      patients.

PMID- 16097639
TI  - Three basic patterns of changes in serum thyroid hormone levels in Graves'
      disease during the one-year period after radioiodine therapy.
AB  - The purpose of this study was to clarify the characteristic patterns of the
      thyroid hormonal changes in Graves' disease during the one-year period after 131I
      therapy considering that few serial hormonal data during this period are
      available in the literature. METHODS: The levels of serum T3, T4 and FT4 before
      and during one year were plotted as a function of time in 70 therapy courses of
      58 patients without subsequent antithyroid or steroid therapy. RESULTS: 35
      euthyroid, 6 hypothyroid and 29 hyperthyroid states were obtained during one year
      after therapy. Although individual patients had individual hormonal changing
      patterns, 3 common basic patterns were observed from baseline to one month
      (early) and thereafter (late), respectively. The early patterns were a decrease
      in 54 (77%), a minimum change in 8 (11.5%) and an increase in 8 (11.5%). The late
      patterns were a stable state after an initial decrease with a bottom followed by
      an increase (valley pattern) in 47 (67%), a stable state after an initial
      increase with a peak followed by a decrease with a bottom and a subsequent re
      increase (mountain pattern) in 12 (17%) and a late stable state after a gradual
      slow decrease without an obvious bottom near or till one year (downhill pattern)
      in 11 (16%). The bottom level and the degree of hormonal recovery from the bottom
      determined the stable euthyroid, hypothyroid or hyperthyroid state in 49 (86%) of
      57 with the valley or mountain pattern. Most of the bottom levels (81%) and
      transient abnormal changes including transient hypothyroidism (93%, 13/14), peak
      or hyperthyroidism (85%, 11/13) and euthyroidism (67%, 10/15) appeared within 6
      months. The post-therapeutic stable euthyroid, hypothyroid or hyperthyroid state
      could be judged from the hormonal patterns in 57% (39/68) from 2.5 to 6 months,
      in 18% (12/68) from 6 to 9 months and in 25% (17/68) thereafter. CONCLUSION:
      Although the changes in thyroid hormones are not constant in Graves' disease
      during one year after 131I therapy, there are three basic patterns; valley,
      mountain and downhill patterns from one month after therapy. The post-therapeutic
      stable state can be judged by the hormonal level recovered from the bottom in
      most patients.

PMID- 16097640
TI  - Regional cerebral blood flow in a patient with Nasu-Hakola disease.
AB  - We report a functional neuroimaging study of a 43-year-old woman with Nasu-Hakola
      disease (NHD). Regional cerebral blood flow (rCBF) images were measured with
      technetium-99m ethyl cysteinate dimer single photon emission computed tomography
      (SPECT). rCBF was decreased in the bilateral frontal lobes and thalamus. This
      finding was consistent with the known underlying neuropathology in patients with
      NHD. Brain SPECT is useful for demonstrating the pathophysiologic brain region in
      patients with NHD.

PMID- 16097641
TI  - Fused pelvic kidneys: "hourglass sign" on Tc-99m DTPA diuresis renography.
AB  - A 13-year-old girl with fused pelvic kidneys detected on ultrasonographic
      examination was referred to our department for a diuresis renography to assess
      urine drainage dynamics and exclude the possibility of urinary tract obstruction.
      Renal scan demonstrated fused pelvic kidneys functioning normally without
      obstruction. The authors present this case to demonstrate the diuresis renography
      findings of the combined position, fusion and rotation anomalies of the kidneys
      that is a rare congenital anomaly of the urinary tract.

PMID- 16097642
TI  - Clinical usefulness of In-111 chloride and Tc-99m Sn colloid scintigraphy in the
      diagnosis of intrathoracic extramedullary hematopoiesis.
AB  - We report a case of intrathoracic extramedullary hematopoiesis associated with
      hemolytic anemia. While the paravertebral localization of the lesions
      demonstrated on CT and MRI was suspicious of intrathoracic extramedullary
      hematopoiesis, In-111 chloride and Tc-99m Sn colloid bone marrow scintigraphies
      showing a bone marrow element of the lesion were useful to confirm the diagnosis.

PMID- 16097643
TI  - Transient crossed cerebellar diaschisis secondary to cerebral hyperperfusion
      following carotid endarterectomy.
AB  - We report a case of transient crossed cerebellar diaschisis secondary to cerebral
      hyperperfusion following carotid endarterectomy. The appearance of crossed
      cerebellar diaschisis under the presence of cerebral hyperperfusion may suggest
      the development of hyperperfusion syndrome.

PMID- 16097644
TI  - Evaluation of exercise-induced acute renal failure in renal hypouricemia using Tc
      99m DTPA renography.
AB  - We present a case of a thirty-eight-year-old man who had exercise-induced acute
      renal failure (exercise-induced ARF). He experienced oliguria, general fatigue,
      and vague discomfort in the lower abdomen after he exercised. As he had suffered
      from hypouricemia before, he was diagnosed as having exercise-induced ARF
      associated with hypouricemia. Enhanced computed tomography (CT) images showed
      patchy wedge-shaped contrast enhancement on his bilateral kidneys, consistent
      with characteristic observations for exercise-induced ARF. Tc-99m diethylene
      triamine pentaacetic acid (DPTA) renography revealed decreases in both the renal
      blood flow (RBF) and glomerular filtration rate (GFR), and revealed parenchymal
      dysfunction of the bilateral kidneys. Renogram revealed a hypofunctional pattern
      on the bilateral kidneys. CT images and Tc-99m DTPA renography also had improved
      when the symptoms of exercised-induced ARF indicated improvement. It has been
      hypothesized that one cause of exercise-induced ARF may be renal vasocontraction.
      Although CT images are useful in evaluating exercise-induced ARF, Tc-99m DTPA
      renography can more easily and safely evaluate renal function. We also show that
      Tc-99m DTPA renography is useful in precisely evaluating the degree of
      improvement of exercise-induced ARF.

PMID- 16097645
TI  - FDG uptake in colonic villous adenomas.
AB  - Colonic adenomas constitute 70-80% of all colorectal polyps, and their clinical
      significance relates primarily to their relationship with colorectal cancer. The
      malignant potential of the polyps detected by FDG-PET is unknown, as not all the
      colonic lesions identified by FDG-PET represent colorectal malignancies. The
      purpose of this study was to investigate the rate of FDG-PET positivity within
      colonic villous adenomas. A pathology database search was performed to identify
      all patients diagnosed with colonic villous adenoma between June 1, 1996 and
      December 1, 2000. Patients with a pathologic diagnosis of colonic villous adenoma
      and who also had a FDG-PET study up to 1 month before colonoscopy were included
      in this study. FDG-PET findings were compared with pathological features. Of more
      than 4,000 patients, six patients were diagnosed with colonic adenoma on
      subsequent colonoscopy following FDG-PET study. Based on the pathological
      findings, these 6 patients had a total of 2 villous and 9 tubulovillous adenomas.
      Five of the 6 patients showed foci of increased FDG uptake in the region of the
      colon that corresponded to the villous adenoma(s) detected on colonoscopy, which
      accounted for a true-positive rate of 83.3% (5/6 subjects). Focal lesions in the
      colon seen on FDG-PET examinations need to be investigated further, even though
      some of these will prove to be villous adenomas rather than colorectal
      carcinomas. Future studies in a larger number of patients are needed to evaluate
      the relationship of histopathological features of colonic polyps and
      detectability of these lesions by FDG-PET.

PMID- 16097646
TI  - Hexokinase-II expression in untreated oral squamous cell carcinoma: comparison
      with FDG PET imaging.
AB  - Hexokinase is thought to be one of the key factors of glucose catabolism in the
      cell. The aim of this study was to investigate the relationship between HK-II
      expression and 18F-fluoro-2-deoxy-D-glucose (FDG) uptake in human untreated oral
      squamous cell carcinoma (OSCC). Pre-operatively FDG positron emission tomography
      (PET) was performed 60 min after FDG injection in all the patients. Maximum
      standardized uptake value (SUV) was used for evaluation of tumor FDG uptake.
      Tumor sections were stained immunohistochemically for HK-II. All the tumor
      sections stained positive for HK-II. Eighteen (95%) tumors in HK-II showed
      immunostained positive area >50%. HK-II findings revealed eleven (58%) tumors
      with strong intensity, six (32%) with moderate intensity and two with weak
      intensity (10%). There was no statistically significant correlation between SUV
      and the expression of HK-II (p = 0.46). In conclusion, OSCC showed increased FDG
      accumulation and overexpression of HK-II. However, we did not find any
      significant relationship between high FDG uptake and overexpression of HK-II in
      this patient population, and thus other properties need to be evaluated in order
      to elucidate key factors responsible for FDG activity in OSCC.

PMID- 16097647
TI  - Detection of cerebrospinal fluid leakage in intracranial hypotension with
      radionuclide cisternography and blood activity monitoring.
AB  - Radionuclide cisternography is an indispensable examination to detect
      cerebrospinal fluid (CSF) leakage in patients suspected of having spontaneous
      intracranial hypotension (SIH). However, it sometimes fails to demonstrate the
      site of CSF leakage, and in such cases, early bladder visualization is utilized
      for the diagnosis of SIH as an indirect finding. The aim of this work is to
      improve the diagnostic ability of radionuclide cisternography and to reevaluate
      the reliability of early bladder visualization as an indirect finding of CSF
      leakage. METHODS: We obtained serial images during the first hour after injection
      as well as the following time points in 4 patients with SIH and 5 with normal
      pressure hydrocephalus (NPH) as a control. We also performed blood sampling over
      time to measure blood radioactivity concentrations. RESULTS: All 4 patients with
      SIH demonstrated leakage, 2 of 4 within one hour after injection. Bladder
      visualization was observed falsely in 4 of 5 patients with NPH, considered to be
      the result of a lumbar puncture complication. In this false bladder
      visualization, blood radioactivity showed a more rapid raise and fall than in CSF
      leakage of SIH. CONCLUSIONS: The combination of radionuclide cisternography,
      including early time points and blood sampling, may enable accurate diagnosis of
      SIH.

PMID- 16097648
TI  - Preparation, radiochemical purity control and stability of 99mTc-mertiatide (Mag
      3).
AB  - BACKGROUND: Scintigraphic image analysis of 99mTc-mertiatide (Mag-3,
      mercaptoacetyltriglycine) clearance provides the determination of the blood flow,
      the tubular transit time and the excretion as well from both kidneys.
      Radiopharmaceutical routine recommends a radiochemical purity control before
      administration of the product to a patient. The main objective of this study is
      to develop a Mag-3 labeling procedure that fits better than the previous one in
      our daily routine production of radiopharmaceuticals. METHODS: Increasing
      proportions of 99mTc-Mag-3 were measured during the heating and cooling steps of
      the Mag-3 labeling procedure. HPLC analysis was used to confirm the results of a
      rapid radiochemical quality control assay on standard ITLC-SG paper. RESULTS: The
      reconstitution time takes 20-25 minutes from the harvest of pertechnetate to a
      ready-for-use calibrated patient syringe. The HPLC profile of 99mTc-Mag-3
      including its minor impurities remains unchanged for 24-48 hours after
      reconstitution. CONCLUSIONS: The application of a programmable Peltier-directed
      device for heating/cooling provides a better control of the temperature course.
      The procedure proposed fully meets the labeling criteria recommended by the
      supplier and can be performed with a minimum of attention within a time-span that
      we formerly needed for solely the radiochemical purity control assay. Moreover,
      99mTc-Mag-3 prepared in this way seems to be considerably more stable than
      mentioned in the manufacturer's instructions.

PMID- 16097649
TI  - Recent work on isozymes in man.

PMID- 16097650
TI  - Malaria and human polymorphisms.

PMID- 16097651
TI  - Genetic basis of abortion.

PMID- 16097652
TI  - The mapping of human chromosomes.

PMID- 16097653
TI  - Recombination within a histocompatibility locus.

PMID- 16097654
TI  - The applications of genetic mosaicism to developmental problems.

PMID- 16097655
TI  - Mutation in eukaryotes.

PMID- 16097656
TI  - Recombination in yeast.

PMID- 16097657
TI  - The genetic organization of chromosomes.

PMID- 16097658
TI  - Genetics and biosynthesis of cytochrome c.

PMID- 16097659
TI  - The morphogenesis of animal viruses.

PMID- 16097660
TI  - Extrachromosomal inheritance: hereditary symbionts, mitochondria, chiloroplasts.

PMID- 16097661
TI  - Genetics of disease resistance in plants.

PMID- 16097662
TI  - Pseudomonas genetics.

PMID- 16097663
TI  - The origin of maize.

PMID- 16097664
TI  - [Magnetic properties and transport behaviors in double doped
      La(0.67+1.33x)Sr(0.33-1.33x)Mn(1-x)Mg(x)O3 system].
AB  - The M-T curves, M-H curves, ESR curves, infrared spectrum, Raman spectrum, rho-T
      curves and MR-T curves of La(0.67+1.33x)Sr(0.33-1.33x)Mn(1-x)Mg(x)O3 (0.00 < or =
      x < or = 0.25) were studied. The experiment pointed out that all samples exhibit
      a paramagnetic-ferromagnetic (PM-FM) transition associated with metallic
      insulating (MI) transition in the low doping region, which does not occur in the
      heavy doping zone. The authors suggest that this behavior is attributed to the
      difference between the Jahn-Teller distortion of the Mn3+ ion neighboring Mg2+
      and that of the Mn3+ ion non-neighboring Mg2+, which is confirmed by the IR and
      Raman spectra. The anomalous transport behavior is dominated by the differerent
      Jahn-Teller distortion.

PMID- 16097665
TI  - [Fabrication and study of sputtered NbN thin films].
AB  - In this work the authors discussed the fabrication of NbN thin films deposited
      using two methods: reactive magnetron sputtering system and DC bias-voltage
      sputtering system. The thickness and the surface morphology of the thin films
      were measured and observed by SEM. The crystalloid structure was analyzed by X
      ray diffraction (XRD). The authors also measured the critical temperature (Tc) of
      the thin films. The authors compared the characters of NbN thin films that the
      authors prepared through two methods. The results showed that the films the
      authors prepared were uniform, compact, well constructed and sing-phase FCC delta
      NbN. It is shown that the deposition temperature and the flux of N2 have a strong
      effect on the preferred orientation, while the critical temperature of the films
      is influenced by the quality of the original vacuum.

PMID- 16097666
TI  - [Energy pooling collisions for K(4P) + Cs(5D) in a K-Cs mixture].
AB  - The rate coefficients for energy-pooling collisions K(4P) + Cs(5D) --> Cs(6S) +
      K(4D, 6S) in the K-Cs vapor mixture were measured relative to a known energy
      pooling rate coefficient of a homonuclear reaction [i. e., Cs(6P) + Cs(5D) -->
      Cs(6S) + Cs (7D(J))]. Populations of the Cs(6P, 5D) and K(4P) states were
      produced by photodissociation of K2 and Cs2 molecules through the use of a dye
      laser radiation. The resulting fluorescence included the direct components
      emitted in the decay of the excited states produced by photodissociation and the
      induced components arising from the collisionally populated states. By combining
      relative intensities of the components with the effective lifetimes of Cs(6P) and
      K(4P) states, the rate coefficients (in units of 10(-9) cm3 x s(-1)) for the
      heteronuclear energy-pooling were found to be 2.6 and 3.6, respectively. The
      contribution to the rate coefficients from other processes are discussed.

PMID- 16097667
TI  - [Mean temperature of electron determined by atomic hydrogen emission line in
      EACVD].
AB  - The process of atomic hydrogen emission in CH4/H2 gas mixture in EACVD is
      simulated by Monte Carlo method. In the simulation the collision between electron
      and H2 molecule has two basic types: elastic collision and inelastic collision.
      Four types of inelastic processes have been considered, namely vibrational
      excitation, dissociation, electron excitation and ionization. For e-CH4
      collision, elastic momentum transfer, vibrational excitation, dissociation,
      ionization and dissociation ionization are considered. The relationship between
      the ratio of atomic hydrogen emission line intensity and mean temperature of
      electron under different CH4 concentration in the gas mixture is investigated. A
      method of determining the mean temperature of electron in situ in the process of
      diamond film deposited by EACVD is given. The result is of great importance to
      depositing high quality diamond films by controlling the conditions of technology
      efficiently.

PMID- 16097668
TI  - [Studies on the relation between the temperature of KTP and the secondary
      harmonic output].
AB  - Using the Nd:YVO4-KTP ring frequency-doubled laser designed by the lab, and
      controlling the laser power current and the crystals temperature accurately, the
      authors obtained the relation between the temperature changes of KTP crystal and
      the secondary harmonic output wavelength while the temperature of YVO4 was
      constant.

PMID- 16097669
TI  - [Photoluminescence spectra of trivalent neodymium doped TiBa glass microspheres].
AB  - In this work, TiBa glass microspheres doped with Nd3+ for morphology-dependent
      resonances of emission were designed and prepared. The emission spectra of TiBa
      glass plate and TiBa glass microspheres (45 and 13 microm in diameter) under 514
      nm excitation were measured. The authors observed many regularly spaced, sharp
      peaks in the emission spectra of a Nd3+-doped glass microsphere. Based on the Mie
      scattering theory, the wavelength separation between the adjacent resonant peaks
      for the 45 microm sphere was calculated to be 3.0 for 810 nm. This value agrees
      well with the observed peak separation (3.1 nm), which indicates the contribution
      of the whispering gallery modes. The emission intensities of a Nd3+-doped TiBa
      glass microsphere (13 microm in diameter) in the 901.69 nm region were plotted
      against the excitation laser power. The emission intensities of the microsphere
      exhibit the linear dependence at the low excitation power (<2 mW). The 901.69 nm
      emission intensity of the microsphere steeply increases at the excitation power
      of 2 mW, which can be ascribed to the laser operation.

PMID- 16097670
TI  - [Study on multi-photon excited fluorescence combined with capillary
      electrophoresis].
AB  - This paper describes a new method, multiphoton excitation fluorescence detection
      combined with capillary electrophoresis separation. The excitation source was a
      self mode-locked femtosecond titanium-sapphire laser (Spectra-physics Inc.),
      producing a stream of pulses with a pulse duration of about 100 fs at 82 MHz
      repetition rate. Its average power was about 200 mW at 750 nm. The laser beam was
      focused into a thin wall flow cell of capillary electrophoresis. A high numerical
      aperture objective (100 x NA 1.25) was chosen to focus the laser beam and to
      collect the fluorescence emitted by detecting molecules. Then the fluorescence
      was detected by a fast response PMT. All data were acquired and processed by a
      microcomputer. For three biological molecules, 5HT, FAD and NADH, it was
      demonstrated that they can be separated and detected efficiently by this method
      with three-photon and two-photon excitation respectively using only one 750 nm
      laser beam. The detection limits were 1.0 x 10(-6) mol x L(-1) for 5HT, 7.4 x 10(
      7) mol x L(-1) for FAD and 9.8 x 10(-7) mol x L(-1) for NADH using the criterion
      of three standard deviations above background. The results are much better than
      those with UV absorption detection by one or two magnitudes.

PMID- 16097671
TI  - [Photoluminescence of nano-SiC annealed by pulse laser].
AB  - Nanocrystalline silicon carbon (nc-SiC) from amorphous silicon carbon films was
      obtained through XeCl excimer laser annealing. The photoluminescence (PL) of the
      nc-SiC was analyzed at different annealing laser energy density. It was observed
      that PL presented a wide luminescence band from 300-600 nm in the nc-SiC films.
      The two main luminescence bands, situated at 398 and 470 nm respectively, are
      attributed to band to band and defect recombination in the 6H-SiC based on the
      structure changes of the nc-SiC films. The relative PL intensity of these two
      bands was determined by the surface state density in the nc-SiC films and their
      irradiative life

PMID- 16097672
TI  - [Multiple emissions in organic electroluminescent device using a mixed layer as
      an emitter].
AB  - A organic electroluminescent device has been fabricated by using a mixed layer as
      an emitter. The configuration of the device is ITO/TPD/TPD: PBD(equimole)/PBD/A1,
      in which TPD (N,N'-diphenyl-N,N'-bis(3-methylphenyl)-1,1'-biphenyl-4,4'-diamine)
      and PBD (2-(4'-biphenyl)-5-(4''-tert-butylphenyl)-1,3,4-oxadiazole) are used as
      hole transport material and electron transport material, respectively. Broad and
      red-shifted electroluminescent spectra related to the fluorescence of constituent
      materials were observed. It is suggested that the monomer, exciplex and
      electroplex emissions are simultaneously involved in EL spectra by comparison of
      the EL with the PL spectra and decomposition of the EL spectrum. The type of
      exciplex is the interaction between the excited state TPD (TPD*) and PBD in the
      ground state, and the type of electroplex is a (D+-A-)* complex by cross
      recombination of hole on the charged hole transport molecule (D+) and electron on
      the charged electron transport molecule (A-). All types of excited states show
      different formation mechanisms and recombination processes under electric field.
      The change of emission strengths from monomer and excited complexes lead to a
      blue-shift of the emissive spectra with an increasing electric field. The maximum
      luminance and external quantum efficiency of this device are 240 cd x (cm2)(-1)
      and 0.49%, respectively. The emissions from exciplex or electroplex formation at
      the organic solid interface generally present a broad and red-shifted emissive
      band, providing an effective method for tuning of emission color in organic
      electroluminescent devices.

PMID- 16097673
TI  - [Research on noninvasive blood glucose measurement with simulate sample by NIR
      spectroscopy].
AB  - The article puts milk forward as simulate sample for blood glucose measurement.
      With the new simulate sample, the authors make deep researches on measuring
      method and wavelength choice in the field of noninvasive blood glucose
      measurement by near-infrared diffuse reflectance spectroscopy. Depending on the
      absorption coefficient of lactose, the authors choose the two wavebands from 1560
      to 1750 nm and form 2090 to 2190 nm. The model was built by partial least-squares
      (PLS), several pretreatment methods (including multiplicative scatter correction,
      first derivative and vector normalization) and different spectral regions were
      compared. The best correlation values for lactose were 0.99 and the best RMSEP
      values for lactose were 0.045. The results provide us with valuable theory
      reference and practical experiences and lead us to next research on noninvasive
      blood glucose measurement.

PMID- 16097674
TI  - [Near infrared spectra (NIR) analysis of octane number by wavelet denoising
      derivative method].
AB  - Derivative can correct baseline effects and also increase the level of noise.
      Wavelet transform has been proven an efficient tool for de-noising. This paper is
      directed to the application of wavelet transfer and derivative in the NIR
      analysis of octane number (RON). The derivative parameters, as well as their
      effects on the noise level and analytic accuracy of RON, have been studied in
      detail. The results show that derivative can correct the baseline effects and
      increase the analytic accuracy. Noise from the derivative spectra has great
      detriment to the analysis of RON. De-noising of wavelet transform can increase
      the S/N and improve the analytical accuracy.

PMID- 16097675
TI  - [Identification of rhubarb samples based on IR spectra by using Takagi-Sugeno
      fuzzy systems].
AB  - Takagi-Sugeno fuzzy system is composed of several back-propagation neural
      networks (BP-NNs), and has some fuzzy logic properties. In this paper, the Takagi
      Sugeno fuzzy logic system is applied to identifying official and unofficial
      rhubarb samples based on their infrared spectra. The effects of the number of
      hidden neurons and the momentum parameters on the prediction were investigated.
      The results obtained by using Takagi-Sugeno fuzzy system were better than those
      by commonly used BP-networks. With a proper network training parameter, 100%
      correctness can be obtained by using Takagi-Sugeno fuzzy system. This method is
      more accurate than the common methods, and is more scientific than traditional
      methods. So it is applied to identifying rhubarb easily and rapidly.

PMID- 16097676
TI  - [Detrended correspondence analysis of phenetic relationships of bryophytes based
      on FTIR spectra].
AB  - Bryophytes are important high plants. However, the plants of bryophyte are small
      in size with few identification characters. The identification of plant samples
      using Fourier transform infrared spectrometer with OMNI collector is simple,
      convenient, fast and accurate. In the present paper, Fourier transform infrared
      spectrometer with OMNI collector was applied to gain the infrared spectra of 30
      samples belonging to 26 bryophyte species. Based on the indices of wave number
      absorbance, the differences of the 30 infrared spectra were compared by the
      method of Detrended Correspondence Analysis (DCA). The results showed that there
      is good correspondence between the position relationship of DCA two-dimensional
      plot of the samples based on the indices of wave number-absorbance of FTIR
      spectra and their classification relationship. Therefore, it is practical to
      apply the infrared spectra to identifying the false sample from the true one in
      medicine bryophytes.

PMID- 16097677
TI  - [Structure analysis on growth solid-liquid boundary layer of BSO crystal at real
      time].
AB  - The micro Raman spectra of solid-liquid boundary layer, the melts and crystal
      side, were measured at real time, concerning BSO crystal grown with zone-melting
      method. The structure characters in boundary layer, melts and crystal were
      analyzed. The process, of which the growth unit structure changed while they
      transited from melts through boundary layer to crystal lattice, was analyzed. The
      results show that, there exists Bi3O4 and [SiO4] bonding structure in the melts
      of BSO crystal. While in the solid-liquid boundary layer, the Bi3O4 molecular
      units converge into [BiO7] octahedron monomer of polymer in form, the monomer or
      the polymer converge with the [SiO4] structure units, then all these converged
      structure enter into crystal lattice sites.

PMID- 16097678
TI  - [Raman spectroscopy studies on the aqueous solutions of sodium formate and
      lithium formate].
AB  - The structures of the aqueous solutions of sodium formate and lithium formate are
      studied according to the growth conditions of the crystals under different
      supersaturations and temperatures by Raman spectroscopy. The effects of
      temperature, concentration, supersaturation and cation on the structures of
      solutions and the structure difference between lithium formate solution and
      lithium formate monohydrate crystal are analyzed. The result shows that the
      concentration, temperature and supersaturation effect the structures of the
      solutions slightly and the cation effects the frequency of the bands greatly.

PMID- 16097679
TI  - [Spectral study on intermolecular coupling interaction and relation to
      microstructure in polyester/inorganic hybrid materials].
AB  - The coupling form of the polymeric-inorganic component and the relation between
      intermolecular special hydrogen bonding interaction and the microstructure of
      crystallizable polymer, as well as micro-phase separation scale in non-covalently
      coupled poly (epsilon-caprolactone) (PCL)/silica (SiO2) hybrid materials were
      investigated by means of Fourier transform infrared (FTIR) spectroscopy,
      ultraviolet-visible (UV-Vis) spectroscopy, wide angle X-ray diffraction (WAXD)
      and differential scanning calorimetry (DSC). The results show that the coupling
      form between PCL and SiO2 mainly depend on a strong intermolecular hydrogen
      bonding interaction in the hybrid system. The hydrogen bonding strength increases
      with increasing TEOS content, while the crystallization of PCL decreases, and the
      optical transparency of hybrid materials increases. In addition, it affects the
      scale of micro-phase separation in hybrid materials.

PMID- 16097680
TI  - [Study on the method to adjust optical fiber's spectrum attenuation with the
      Fourier transform].
AB  - A method based on Fourier transform to compensate the non-linear attenuation of
      optical fiber used as a probe in a spectrum-collecting system was proposed. First
      the output electric currents of photoelectric tube with and without fiber were
      transformed to the frequency field. So an adjustable function in frequency field
      was obtained, and the adjustable function was transformed to the spectrum field,
      so the final adjustable function was obtained. A photoelectric system was
      designed for testing. With visible light, this method can make the error rate of
      fiber transmission as low as less than 1.54%. It is proved that the method is fit
      for adjusting some optical fiber spectrum attenuation.

PMID- 16097681
TI  - [Hydrogen-bond state analysis of cellobiohydrolase I molecule from Trichoderma
      viride].
AB  - Hydrogen-bond states on cellobiohydrolase II (CBH II) of Trichoderma viride were
      analysed by laser Raman spectroscopic method used to reveal molecular normal
      modes of vibration character. The results indicated that hydrogen-bond ability of
      carbonyl oxygen-atom of amide I was raised in two types of aqueous solution
      samples (6.0 and 8.0 of pH value) compared to the solid sample. The variation
      trend of beta structure modes was similar between amide II and amide I. As far as
      the ability of hydrogen-bond forming is concerned, tryptophan (Trp) and tyrosine
      (Typ) residues are strong hydrogen proton donor in pH 6.0 and solid sample, thus
      proving the results of previously spatial structure analysis. By analysis of free
      S-H character, the -S-S- construction in Trichoderma viride mature peptide has
      been proved to be the same as that of Trichoderma reesei.

PMID- 16097682
TI  - [Ion solvation and ion association in high-concentration of NaBF4/DMF solutions].
AB  - Ion solvation and ion association in solutions of NaBF4/DMF were studied by
      infrared and Raman spectroscopy and ab initio quantum chemistry. It was found
      that the sodium cation interacts on oxygen atom of C=O group in DMF molecules.
      The solvation number of Na+, four, was obtained according to the change analysis
      of CH3 rocking band. The splitting of the nu1 mode of BF4(-) anion indicates the
      presence of contact ion pairs. Ionic association degree increases with increasing
      molality of the salt. The solvated structure of Na+ and the geometry of Li+ BF4(
      ) ion pair were also suggested based on the ab initio calculations.

PMID- 16097683
TI  - [Synthesis of Ag2S nanoparticles at room temperature and their characterization
      with XPS].
AB  - Nanocrystalline silver sulfide was successfully synthesized at room temperature
      and ambient pressure via a novel, safe, convenient and inexpensive redox
      reaction, using silver oxide, sulfur and polyformaldehyde as reactants and
      ethylenediamine as solvent. The products were characterized with XPS, XRD and
      TEM. XRD spectrum demonstrates a monoclinic Ag2S; TEM shows the products are rod
      like nanoparticles with average diameter of 100 nm, its corresponding SAED
      reveals clear diffraction spots indexed as (120) and (303); XPS confirms the
      formation of Ag2S and indicates the sample's surface stoichiometry of
      Ag:S=1:0.453. The control experiments show polyformaldehyde and ethylenediamine
      are both important in the formation of products. Ethylenediamine accelerates the
      reactions via dissolving silver oxide and sulfur and neutralizing the by-product
      formic acid.

PMID- 16097684
TI  - [Direct determination of Nb in titanium oxide using slurry sample introduction by
      axial viewing inductively coupled plasma optical emission spectrometry].
AB  - By using dispersant polyacrylate amine (NH4PAA) to disperse TiO2, effects of
      different dispersants, pH value and the amount of dispersant on TiO2 slurry were
      investigated. The pH value of the medium and the dispersant amount were
      optimized, and a stable and homogeneous suspension was prepared. Nb in TiO2 was
      determined by an axial viewing ICP-OES spectrometer. At the same time, the
      performance of the axial viewing ICP-OES using solid powder analysis was
      discussed. Under the optimum experimental conditions, the detection limit of the
      present method is 3.0 microg x L(-1) and the RSD is 3.1% (n = 3, c = 0.3 mg x L(
      1)).

PMID- 16097685
TI  - [Determination of constant and trace elements in Ranunculus ternatus thunb by ICP
      AES].
AB  - The determination of twenty one kinds of constant and trace elements in Chinese
      herb Ranunculus ternatus thunb was performed by ICP-AES. The results show that K,
      Fe, Ca, Cr, Mg, Mn, Zn, Co, Cu, Ni, Se and Sr are relatively rich in Ranunculus
      ternatus and the content of Pb, Cd and As are very low. The ratio of the content
      of Zn to that of Cu is about 3, which is consistent with the relative content
      level of Zn and Cu contained in many anticancer Chinese traditional plants.

PMID- 16097686
TI  - [Comparison of different digestion methods used for the decomposition of plant
      samples in elemental quantification by using ICP-AES].
AB  - Four digestion methods were used for the decomposition of plant samples. The
      contents of Al, B, Ba, Ca, Cu, Fe, K, La, Mg, Mn, Na, P, Pb, Sr, Ti and Zn in the
      two Standard Reference Materials 1573a (Tomato Leaves) and 1575 (Pine Needles)
      were determined by using ICP-AES and the determined values were compared with the
      certified ones. It was demonstrated that hydrofluoric acid is of vital importance
      in the decomposition of plant samples, because it can remove silicious materials
      from the matrix. Appropriate selection of digestion methods can improve greatly
      the accuracy of elemental quantification in plant samples.

PMID- 16097687
TI  - [GFAAS determination of trace amount cadmium in chitosan by micro wave].
AB  - In this work, a method had been developed for determination of cadmium in
      chitosan by means of graphite furnace atomic absorption spectrometry with micro
      wave digestion, a systematic study was carried out by selection of the most
      appropriate working conditions and optimization of the sample mass. The samples
      were digested by micro wave with mixed acid of HF-HClO4 (1:2). Trace amount
      cadmium has been determined by Graphite Furnace Atomic Absorption Spectrometry
      (GFAAS) with Pd(NO3)2 as a matrix modifier. If appropriate working conditions are
      chosen, the method finally proposed shows interesting features for the
      determination of the analytics in the samples such as: suitable precision values
      (R. S. D--2.8%) and the recover rate by standard addition is 97.0%-106.3%. The
      method is simple, rapid and with accurate results.

PMID- 16097688
TI  - [Direct determination of trace lead in chestnut by graphite furnace atomic
      absorption spectrometry with slurry sampling].
AB  - A method for the direct determination of trace lead in chestnut by Graphite
      Furnace Atomic Absorption Spectrometry (GFAAS) with slurry sampling was developed
      in the present paper. Ammonium ortho-phosphate was used as a matrix modifier. The
      effects of slurry preparation, particle size of sample, matrix modifier, ashing
      temperature, atomization temperature, and common coexisting components on the
      determination of lead were studied. Under the optimized operating conditions, the
      detection limit, the relative standard deviation (RSD), and the recoveries of
      standard addition for this method were 0.47 ng x mL(-1), 6.1% (n = 11) and 90%
      106%, respectively.

PMID- 16097689
TI  - [Determination of Pb and Al in blood and hair of child using transverse heated
      graphite furnace atomic absorption spectroscopy].
AB  - Pb and Al in blood and hair of child were determined by transverse heated
      graphite furnace atomic absorption spectrometry with NH4H2PO4 and Mg(NO3)2 as a
      modifier, which enhanced the temperature of ashing, eliminated the matrix
      interference and memorial effect. The method is rapid, simple and accurate. The
      characteristic mass of the method was 2.3 x 10(-11) g and 2.2 x 10(-11) g for Pb
      and Al respectively. The relative standard deviation of Pb and Al was 3.0% and
      11.4%, respectively, and the recovery was 96%-102%.

PMID- 16097690
TI  - [Determination of trace cobalt in water samples by graphite furnace atomic
      absorption spectrometry after cloud point].
AB  - In buffer solution of citric acid monohydrate-disodium hydrogen phosphate at pH 5
      7.5, cobalt water samples were chelated by 1-(2-pyridylazo)-2-naphthol (PAN) to
      form Co-PAN. After water-bath at 66 degrees C for two hours, Co-PAN is extracted
      into Triton X-100 nonionic surfactant phase and separated from bulk water.
      Extracted cobalt content was measured by graphite furnace atomic absorption
      spectrometry. The surfactant phase separated was treated with 0.5% HNO3-0.1%
      Pd(NO3)2 to remove background interference at 1200 degrees C temperature. The pre
      concentration of cobalt in water samples permitted the detection of 0.003 microg
      x L(-1) (10sigma) with the enhancement factor of 100. The recoveries were 90.5%
      106%. The proposed method was applied to the determination of cobalt in water
      samples and satisfactory results were obtained.

PMID- 16097691
TI  - [Spectroscopic studies on different chemical composition between the shell and
      core of Radix Notoginseng].
AB  - Notoginseng (Sanqi) is one of the most important components of famous Chinese
      recipe (Yunan Baiyao) and possesses a wide variety of applications in clinical
      practice. It has been found that Sanqi of different size exhibits different
      curative effects. Such a phenomenon may be attributed to that the chemical
      constituent from shell region is different from that of core region. To prove the
      above-mentioned hypothesis, Ultraviolet-Visible (UV-Vis), FTIR, fluorescence
      spectroscopy, together with high performance liquid chromatography (HPLC) and
      electrospray ionization mass spectroscopy (ESI-MS) were utilized to study the
      variation of chemical compositions from shell and core regions of Sanqi. The
      results demonstrate that the chemical compositions of Sanqi from shell and core
      regions are different. In summary, differences in chemical composition between
      Sanqi shell and core were manifested from versatile aspects. Such differences
      shed a light on the different curative effects of Sanqi.

PMID- 16097692
TI  - [Fluorescence spectra and protonation of ofloxacin].
AB  - Fluorescence spectra, ultraviolet spectra and protonation of Ofloxacin (OFL) at
      different pH values have been studied. In strong acidic solutions, OFL molecule
      might accept two protons to exist as ternary acid H3L2+ with a maximum emission
      wavelength (lambdamax) at 505 nm. Along with the increase in pH value,
      fluorescence spectrum of OFL changed, an iso-fluorescence point at 352 nm was
      found in the fluorescence excitation spectra, and at the same time, isosbestic
      points were found in its UV absorption spectra. This spectral feature reveals
      that H3L2+ gradually lost hydrogen ion combined on C-4 keto oxygen. In the range
      of pH 2.5 to pH 4, OFL exists as H2L+ with lambdamax at 499 nm. When pH>4, the
      fluorescence emission peak at 499 nm gradually blue-shifted to 455 nm as pH was
      increasing, and an iso-fluorescence emission point was formed at 484 nm,
      indicating the dissociation of hydrogen ion of carboxylic acid at C-3. At about
      pH 7.0, OFL exists in the dipole ion form HL with lambdamax at 455 nm, which is
      the strongest fluorescence form. When pH>8, lambdamax red-shift from 455 to 475
      nm as pH increases, meanwhile, fluorescence intensity decreases, indicating that
      HL lost hydrogen ion combined on N-4 of piperazinyl group. When pH>10, OFL exists
      in anion ion form L-, and fluorescence intensity decreases with pH increasing,
      but lambdamax remains essentially constant, indicating that medium environment
      influences the fluorescence property of OFL.

PMID- 16097693
TI  - [Simultaneous determination of aspirin and salicyclic acid by synchronous
      fluorescence spectrometry].
AB  - A simple, rapid and inexpensive fluorimetric method for simultaneously
      determining ASA and SA in a single scan of the co-existing specimen had been
      established. When the wavelength interval (delta lambda) is 80 nm for scaning,
      the amounts of ASA and AS could be quantitatively determined respectively. The
      fluorescence intensity was linearly related to the aspirin concentration in the
      range of 4.0 x 10(-6)-1.0 x 10(-4) mol x L(-1) with correlation coefficient
      0.9949; the fluorescence intensity was linearly related to the salicyclic acid
      concentration in the range of 8.0 x 10(-7)-1.0 x 10(-4) mol x L(-1) with
      correlation coefficient 0.9975, the determination limit was 4.0 x 10(-7) mol x L(
      1). The method is simple, rapid and inexpensive, it can be used for medicament
      analysis.

PMID- 16097694
TI  - [Study on the inclusion interaction of water-soluble p-(N,N-dimethylamino)
      calix[8]arene with diphenylamine-4-sulfonic sodium salt].
AB  - The inclusion interaction of water-soluble p-(N,N-dimethylaminomethyl)
      calix[8]arene with diphenylamine-4-sulfonic acid sodium salt was investigated by
      fluorimetric method. When diphenylamine-4-sulfonic acid sodium salt was added
      into the p-(N,N-dimethylaminomethyl)-calix[8]arene solution, the emission
      spectrum of diphenylamine-4-sulfonic acid sodium salt occurred to a blue shift
      with the enhancement of the fluorescent intensity. The results show that the
      formation of the inclusion complex of the p-(N,N-dimethylaminomethyl)
      calix[8]arene with diphenylamine-4-sulfonic acid sodium salt. The influence
      factors such as the pH value of solutions, solvents on the emission and
      excitation spectra of the inclusion complex were studied. It indicates that
      diphenylamine-4-sulfonic acid sodium salt penetrated the cavity of the
      calix[8]arene via the static action between the sulphonyl group of diphenylamine
      4-sulfonic acid sodium salt and nitrogen atom of p-(N,N-dimethylaminomethyl)
      calix[8]arene and the hydrophobic interaction of the aromatic rings.

PMID- 16097695
TI  - [Synthesis of purpure-18-imide and study on its interaction with bovine serum
      albumins by fluorescence].
AB  - Purpure-18-imide was synthesized based on the porphyrin's special affinity for
      cancer cells and the antitumor activity of pyrrolidine compound. The binding
      reaction between purpure-18-imide and bovine serum albumins (BSA) in aqueous was
      studied by fluorescence and UV-Vis absorption spectra. The research results
      indicated that the combination reaction of them was a single static quenching
      process. In aqueous, purpure-18-imide strongly bound BSA with molar ratio of 1:1.
      The binding constant K0 was 5.386 x 10(5) L x mol(-1). The shortest binding
      distance (r = 3.54 nm) and energy transfer efficiencies (E = 0.26) between donor
      (BSA) and acceptor (purpure-18-imide) were obtained by Forster's nonradiative
      energy transfer mechanism.

PMID- 16097696
TI  - [Determination of ascorbic acid by indirect fluorimetry].
AB  - Experiments indicated that cerium(IV) ion which could not emit fluorescence was
      deoxidized by ascorbic acid to cerium(III) ion which could emit its
      characteristic fluorescence in water solution, while sodium hexametaphosphate
      added could greatly enhance the fluorescence intensity of the system. From this,
      an indirect sensitive method for determining ascorbic acid was developed. The
      fluorescence intensity of the system was measured in a 1 cm quartz cell with the
      excitation and emission wavelengths of 303 and 340 nm, respectively. The results
      showed that the fluorescence intensity of the system presented a linear
      relationship with the concentration of ascorbic acid in the range of 1.0 x 10(-7)
      8.0 x 10(-6) mol x L(-1), the correlation coefficient r was 0.9997, and the
      detection limit (S/N = 3) was 1.6 x 10(-8) mol x L(-1). The presented method was
      used to determine ascorbic acid sample and vitamin C tablet, and the results were
      satisfactory.

PMID- 16097697
TI  - [A study on the ultraviolet spectra of halogenated benzoylferrocenes].
AB  - The ultraviolet spectra of all of the o, m, p-halogenated benzoylferrocenes have
      been studied the following rules obtained: 1. The lambdamax of the ultraviolet
      spectrum R band and K band for the isomers is lambdamax(m-X) > lambdamax(p-X) >
      lambdamax(o-X). 2. With the same substituted positions of the different halogen
      on the benzene ring, the lambdamax of the ultraviolet spectrum K band is
      lambdamax(C1) > lambdamax(Br) > lambdamax(I) > lambdamax(F), then, the lambdamax
      of ultraviolet spectrum R band is lambdamax(I) > lambdamax(Br) > lambdamax(Cl) >
      lambdamax(F).

PMID- 16097698
TI  - [The study of protoporphyrin IX metabolism in cell proliferation using yolk as
      the target samples].
AB  - In order to find the better target sample to investigate protoporphyrin IX
      metabolism in the cell proliferation process in chick embryos, the emission
      spectra of egg white, yolk and urine from non-incubated and incubated eggs were
      measured under the excitation at 405 nm. It was observed that, among the three
      components investigated, only yolk sample was possible to get in pureness almost
      through the whole incubation process. Furthermore, compared with the egg white,
      the yolk had more obvious characteristic emission of protoporphyrin IX and lower
      background spectra and turned to be the better target sample for the
      investigation. The relative characteristic emission intensity of PpIX of yolk
      samples was used to determine the level of PpIX metabolism. It was found that the
      relative emission intensity increases during the first 10 days of proliferation
      process, indicating an increase in the concentration or in the metabolism level
      of protoporphyrin IX. The relative emission intensity, hence the PpIX metabolism
      level, then decreased gradually during the rest days of proliferation process.
      These results are similar to those obtained on human malignant tumors as they
      develop. The result testifies the point of view further that the abnormity of
      PpIX metabolism is correlative to the rapid limitless cell proliferation.

PMID- 16097699
TI  - [Study on the mechanism of the interaction of methylene blue and sulfation
      pachymaran].
AB  - In order to understand the mechanism of the interaction of sulfate
      polysaccharides and small molecules at molecular level, the structure of
      pachymaran was decorated by Wolfrom, and sulfation pachymaran (SP) was prepared.
      The maximum binding number (N = 54) and the binding equilibrium constant (K =
      1.563 x 10(6)) of the sulfation pachymaran and methylene blue (MB) were obtained
      by the exoterica model. The influence of the molar ratio of MB/SP, ethanol,
      hydroxypropyl-beta-cyclodextrin, Triton X-100 and NaCl on the spectra of MB-SP
      complex was investigated. The mechanism of the color changes of methylene blue
      and sulfation pachymaran reaction system has been discussed. The authors draw the
      conclusion that the color changes result mainly from the hydrophobic interaction
      between methylene blue molecules binding on sulfation pachymaran on the base of
      the electrostatic interaction of methylene blue and sulfation pachymaran.

PMID- 16097700
TI  - [Instant effect of temperature on the oxygen carrying capacity of single living
      intact red blood cell].
AB  - The instant effect of temperature on the absorption spectra of the hemoglobin in
      single living intact red blood cells was investigated, by employing a highly
      sensitive fast multi-channel micro-spectrophotometer system to perform non
      invasive, in situ, real time measurements on the cells. It was found that both
      the heights and position of the specific peaks in the absorption spectra of
      intercellular hemoglobin were changed with temperature, indicating that the
      oxygen carrying capacity of red blood cells varies with temperature. The
      correlations of the structure and concentration as well as the function of
      hemoglobin, and the molecular mechanism were also discussed.

PMID- 16097701
TI  - [Ratio spectrophotometry and its application to assay of compound pharmacy
      preparations].
AB  - The present paper is to study ratio spectrophotometry for its application to the
      assay of compound pharmacy preparations. According to the feature of ratio
      spectra, the wavelength pair was selected at the peak point or valley point of
      ratio spectra to establish ratio spectrophotometry for the determination of Co
      Chlorzoxazone tablet and injection of caffeine and sodium benzoate. The average
      recoveries and relative standard deviations for Chlorzoxazone and paracetamol
      were 100.0% and 1.28%, and 100.0% and 0.84%, respectively; the average recoveries
      and relative standard deviations for caffeine and sodium benzoate were 99.98% and
      0.70%, and 99.91% and 0.78%, respectively. It is concluded that as long as the
      ratio spectra exhibit at least one peak and one valley, the results are
      satisfactory.

PMID- 16097702
TI  - [Comparison of non-protected fluid room temperature phosphorescence and micellar
      stabilized room temperature phosphorescence properties of indole-3-butyric acid].
AB  - For indole-3-butyric acid (IBA), the non-protected fluid room temperature
      phosphorescence (NP-RTP) and the fluid room temperature phosphorescence with
      polymeric dispersant polyethyleneglycol-200 (PEG-200), PEG-400 or non-ionic
      surfactant Tween-20, Tween-40, Tween-80, Tween-85, Brij35 and emulsifier OP as a
      medium have been studied in detail. When the surfactants or polymeric dispersants
      were added to the NP-RTP system, the profile of RTP spectrum was not changed, but
      the RTP intensity and the pre-irradiation time required to attain a stable RTP
      signal were increased. Whether the surfactants or polymeric dispersants were
      added to the system or not, no RTP signal was observed when TlNO3 was used as a
      heavy atom perturber (HAP), but intense RTP emissions were observed when KI was
      present as HAP. Recoveries of 95.2%-104% with relative standard deviations of
      2.4%-4.0% were obtained in spiked water and soil samples.

PMID- 16097703
TI  - [Research development of spectroscopic probes of protein].
AB  - A review on the recent research progress in spectroscopic probes of protein was
      presented and discussed. The review included categories of spectroscopic probes
      of protein, interaction models of protein and spectroscopic probes, interaction
      force of protein and spectroscopic probes, and protein conformation research.
      Future research direction of spectroscopic probes of protein was forecast.

PMID- 16097704
TI  - [Optical detection system for micro biochemical analyses].
AB  - For the need of biochemical chip, which consumes fewer specimens and is easy to
      integrate with micro-fluid chip, two kinds of spectrophotometric analysis methods
      are described in the present paper. Both the direct detection method and
      evanescent wave detection method are used in the experiments with visible light
      (460-800 nm). The experimental results proved that the direct detection is simple
      and evident; on the other hand the evanescent wave detection method consumes much
      less reagent and is easy to integrate with microchips.

PMID- 16097705
TI  - [Analysis of spectral properties of novel holographic transmission notch filter].
AB  - Optical filter has extremely important applications in spectroscopy, optical
      measurement and laser physics. Holographic filter, especially the transmission
      volume holographic notch filters using dichromate gelatin (DCG), is a new kind of
      filter with the main characteristic of a very narrow bandwidth. In this paper,
      measurements were carried out on the spectral properties of this transmission
      volume holographic notch DCG filter using an ultraviolet-visible transmittance
      spectrometer. The experimental results show that the relative transmittance of
      main spectrum of this filter is less than 2% in the visible region between 400
      and 800 nm, and the relative transmittance of other spectra are more than 85%.
      Moreover, the filter has a narrow bandwidth with a half-bandwidth less than 12
      nm, and a 1/10 width of the bandwidth less than 15 nm. These results indicate
      that this new kind of filter has an excellent filter characteristic to the main
      spectrum of Ar+ laser at the wavelength of 514.5 nm.

PMID- 16097706
TI  - [Transurethral ablation (Precision Plus) in the treatment of patients with benign
      prostatic hyperplasia].
AB  - Benign prostatic hyperplasia (BPH) is a common condition among elderly men.
      Transurethral needle ablation of the prostate (TUNA) is a minimally invasive
      procedure for treatment of BPH. With TUNA, the inner region of the prostate is
      selectively ablated with temperatures approaching 90-100 degrees C while
      prostatic urothelium is preserved. The TUNA (Precision Plus) was used in 9
      patients with BPH: 1 patient had acute urinary retention, 6 ones had suprapubic
      catheter and 2 patients had lateral and median lobes. The patient with acute
      urinary retention and 4 patients with suprapubic catheter resumed voiding after
      TUNA. Two patients with lateral and median lobes showed improvement of subjective
      and objective parameters. The size of the prostate did not change one month after
      TUNA. Thus, TUNA is a safe and effective therapy for treatment of BPH that can be
      performed with local anaesthesia.

PMID- 16097707
TI  - [Combined therapy of voiding irritative disorders after surgical treatment of
      benign prostatic hyperplasia with Andro-Gin].
AB  - The results of operative and rehabilitative treatment of benign prostatic
      hyperplasia (BPH) was analysed for 69 BPH patients with postoperative irritative
      disorders of voiding. The patients were divided into four groups by
      rehabilitative therapy: group 1 received antibacterial therapy; group 2-
      antibacterial therapy+alpha-adrenoblockers; group 3--antibacterial
      therapy+transrectal laser and magnetic physiotherapy; group 4--antibacterial
      therapy+alpha-adrenoblockers+transrectal laser and magnetic physiotherapy. The
      worst result was obtained in group 1, the best one in groups 3 and 4 (the
      response was compatible). Thus, the addition of physiotherapy to the complex of
      postoperative rehabilitation of patients operated for BPH is justified and
      provides treatment improvement.

PMID- 16097708
TI  - [Mixed forms of urinary incontinence in women: diagnosis and treatment].
AB  - In our clinic we encountered a mixed form of urinary incontinence (UI) in 27%
      patients. The urodynamic examination has detected hyperactive urinary bladder in
      42.2% patients with mixed UI. The patients received conservative therapy in
      combination with replacement hormone therapy and exercise strengthening pelvic
      fundus muscles. A response was achieved in 69% cases. If the imperative component
      was not confirmed by urodynamic testing, the patient was treated surgically. 12
      patients (21%) developed imperative disorders of voiding in early postoperative
      period, 8 (14%) patients' condition deteriorated. Thus, in mixed incontinence
      much attention should be given to clinical manifestations of the disease to avoid
      recurrent imperative disorders of voiding after operative treatment.

PMID- 16097709
TI  - [Kornam in the treatment of imperative urine incontinence in females].

PMID- 16097711
TI  - [Cystourethroanastomosis in extended obliterations and strictures of the
      posterior urethra in men].
AB  - The authors review short- and long-term clinical results of surgical treatment of
      extended urethral strictures and obliterations. A new vesicourethral anastomosis
      was created by novel technique with longitudinal suturing of the neck of the
      urinary bladder. A scheme of the operation is presented. Causes necessitating
      this plastic intervention are analysed. Variants of possible urine incontinence
      after operation depending on etiological cause of the stricture or obliteration
      of the posterior urethra in males are considered.

PMID- 16097710
TI  - [Causes of erectile dysfunction after transurethral resection of hyperplastic
      prostate and its prophylaxis].
AB  - The study was made of 60 sexually active patients with prostatic hyperplasia
      after monopolar transurethral operations (mean age 61.3 years). 30 patients
      entered a control group, 30 ones--the study group. The latter received 10 mg
      vardenafil each other day for 7 weeks after the intervention. The patients filled
      in questionnaire, underwent dopplerography and electromyography of the penis.
      Questionnaire said that erection was worse after operation in 6 (20%) patients (p
      < 0.01) of the control group and none of the study group. The latter also showed
      better circulation. All the men with postoperative erectile dysfunction (ED) had
      electromyographic signs of impaired autonomic innervation of the penis. Thus, ED
      after transurethral operations for prostatic hyperplasia is primarily neurogenic
      and is seen in 20% operated patients. Early vardenafil therapy is effective in
      prevention of postoperative ED.

PMID- 16097712
TI  - [Surgical treatment of neuromuscular dysplasia of the ureter].
AB  - Ten clinical cases of neuromuscular dysplasia of the ureter (NMDU) are reported.
      Eight patients were young (24-38 years), two--of the middle age (41-58 years).
      NMDU was bilateral in two patients. Ureteral achalasia of the congenital solitary
      kidney occured in one case. One 28-year-old female with megaureter of the
      solitary kidney had interstitial cystitis. Clinical picture of the disease was
      characterized primarily with acute pyelonephritis, pain and secondary
      urolithiasis. Surgical treatment consisted in resection of the affected part of
      the ureter with modeling of the lumen of the latter on the drainage and Boari
      plastic repair. Bilateral Boari operation was made in 2 patients. In one case of
      ureteral achalasia and ureterocele direct ureterocystoanastomosis was created
      with good result. Sigmocystoplasty with transplantation of the solitary kidney
      ureter into the intestinal transplant was made in the patient with scar
      contracture of the detrusor and megaureter. Functional result of the operation
      was good. Complications were registered in 4 patients, 2 of which were
      reoperated. In nine patients of ten good and satisfactory functional results were
      obtained.

PMID- 16097713
TI  - [Urodynamic parameters of fetal lower urinary tract in physiological pregnancy].
AB  - The study of urodynamic parameters in 76 fetuses in physiological course of
      pregnancy at gestation term from 20 to 40 weeks has shown that urodynamics of the
      lower urinary tract in the prenatal period directly correlate with embryon and
      fetus formation. Urodynamic indices of fetal lower urinary tract have 13
      significant correlations out of possible 43, indicating distinct interactions of
      various organs and strictures of fetal urinary system. The analysis of the
      structure of correlations between different urodynamic indices of the lower
      urinary tract of the fetus demonstrates that they vary greatly in pregnancy
      trimester II and remain constant in trimester III. Thus, interrelations between
      basic urodynamic parameters of the lower urinary tract get established to the end
      of trimester II.

PMID- 16097714
TI  - [Treatment of ureterocele in children].
AB  - Twenty six patients (15 children and 11 adults) with ureterocele were treated.
      Heterotopic ureterocele prevailed over common forms in children while in adults-
      vice versa (66.7 and 33.3% versus 27.3 and 72.7%, respectively). Recurrences of
      ureterocele are rather frequent. Modified surgical correction of ureterocele is
      proposed which consists in intravesical mobilization of ureterocele together with
      a terminal part of the ureter followed by resection and its transverse re
      implantation with antireflux defense. Such therapeutic policy facilitates
      performance of the operation and enhances reliability of the closing antireflux
      mechanism. Endoscopic correction of ureterocele with one-stage lithoextraction
      was made in 7 adult patients who had undergone transverse dissection of
      ureterocele, in large ureterocele--partial resection of the lower part. The
      residual upper part operates as a closing valve in filling of the urinary
      bladder. Long-term results (3-year follow-up maximum) were studied in 23
      patients. Dissection of ureterocele with ureterocystoneostomy was associated with
      recurrences in 37.6% patients. The best results were achieved in plastic modified
      operations and endoscopic correction of ureterocele. A persistent clinical effect
      was seen in all the patients.

PMID- 16097715
TI  - [Intravesical plastic reconstruction of the ureter in orthotopic ureterocele].

PMID- 16097716
TI  - [The role of urogenital infections in etiology of cystitis and non-obstructive
      pyelonephritis in females. Part 2].

PMID- 16097717
TI  - [Risk, incidence rate and prevention of ureteral injuries in clinical practice].

PMID- 16097718
TI  - Bipolar disorder: disease burden.
AB  - Bipolar disorder is a chronic, severe, recurrent mood disorder. Traditional
      estimates of the prevalence of the disorder may underestimate the actual total
      disease burden. The condition can occur across a wide spectrum of ages, but the
      most common age of onset appears to be between the ages of 15 and 19. Bipolar
      disorder is often underdiagnosed or misdiagnosed, with profound negative clinical
      and economic consequences. Medical and psychiatric comorbidity is common in
      patients with bipolar disorder. Functional disability because of bipolar disorder
      is comparable with that of many chronic medical conditions. It has been estimated
      that the total annual societal cost of bipolar disorder may be as high as 45
      billion dollars.

PMID- 16097719
TI  - Bipolar disorder--costs and comorbidity.
AB  - Not only is bipolar disorder a chronic, severe psychiatric disorder, it is also
      expensive to treat and expensive to society. An estimate of the total cost of
      bipolar disorder made more than a decade ago was as high as 45 billion dollars
      per year. Most of this cost is accounted for by indirect costs related to reduced
      functional capacity and lost work. Patients with bipolar disorder have higher
      rates of utilization of healthcare resources compared with the general population
      and compared with patients with other types of psychiatric conditions.
      Comorbidity contributes to the heavy burden that bipolar disorder imposes on
      society. Bipolar disorder frequently occurs together with other psychiatric
      disorders, especially anxiety disorders and substance abuse. In addition, bipolar
      disorder has been associated with a variety of general medical conditions, which
      further complicate management of the psychiatric disorder.

PMID- 16097720
TI  - Bipolar disorder and work loss.
AB  - Bipolar disorder affects many aspects of an individual's life and greatly
      interferes with a person's ability to find and maintain employment. The evidence
      indicates that a majority of patients with bipolar disorder are not employed and
      many others are employed only part time. Job-related difficulties are common, and
      patients with bipolar disorder tend to have higher rates of absenteeism from work
      compared with working individuals without bipolar disorder. A limited amount of
      data suggests that appropriate treatment may improve occupational status among
      patients with bipolar disorder. The ability to work is closely related to
      functional recovery, which tends to be incomplete in a majority of patients with
      bipolar disorder.

PMID- 16097721
TI  - Cytogenetic analysis of the neotropical spider Nephilengys cruentata
      (Araneomorphae, Tetragnathidae): standard staining nors, C-bands and base
      specific fluorochromes.
AB  - The aim of this work is to characterize Nephilengys cruentata in relation to the
      diploid number, chromosome morphology, type of sex determination chromosome
      system, chromosomes bearing the Nucleolar Organizer Regions (NORs), C-banding
      pattern, and AT or GC repetitive sequences. The chromosome preparations were
      submitted to standard staining (Giemsa), NOR silver impregnation, C-banding
      technique, and base-specific fluorochrome staining. The analysis of the cells
      showed 2n = 24 and 2n = 26 chromosomes in the embryos, and 2n = 26 in the ovarian
      cells, being all the chromosomes acrocentric. The long arm of the pairs 1, 2 and
      3 showed an extensive negative heteropycnotic area when the mitotic metaphases
      were stained with Giemsa. The sexual chromosomes did not show differential
      characteristics that allowed to distinguish them from the other chromosomes of
      the complement. Considering the diploid numbers found in N. cruentata and the
      prevalence of X1X2 sex determination chromosome system in Tetragnathidae, N.
      cruentata seems to possess 2n = 24 = 22 + X1X2 in the males, and 2n = 26 = 22 +
      X1X1X2X2 in the females. The pairs 1, 2 and 3 showed NORs which are coincident
      with the negative heteropycnotic patterns. Using the C-banding technique, the
      pericentromeric region of the chromosomes revealed small quantity or even absence
      of constitutive heterochromatin, differing of the C-banding pattern described in
      other species of spiders. In N. cruentata the fluorochromes DAPI/DA, DAPI/MM and
      CMA3/DA revealed that the constitutive heterochromatin is rich in AT bases and
      the NORs possess repetitive sequences of GC bases.

PMID- 16097722
TI  - Thie expression of an intraspecific aggressive reaction in the face of a stressor
      agent alters the immune response in rats.
AB  - The repercussion on the immune response of the expression of intraspecific
      aggressiveness in the face of a stressor agent was investigated in rats. Ninety
      day-old animals were divided into three groups: the control group (only
      immunological measurements were performed), the foot-shock (FS) (animals
      individually receiving FS), and the intraspecific aggressive response (IAR) group
      (animals receiving FS and presenting IAR). For immunological measurements, blood
      samples were collected promptly at 7 and 15 days after FS or IAR. The FS reduced
      the total leukocyte amount presented. However, aggressiveness triggered not only
      reduction of the leukocytes, but also lymphocyte decrease and neutrophil
      increase. Moreover, an elevation in total leukocytes associated with an increase
      in the humoral immune response was also observed one week after IAR. In this
      study, the expression of intraspecific aggressiveness in the face of a stressor
      seemed to activate the immune system and to potentiate the antigen specific
      humoral response.

PMID- 16097723
TI  - Meals for two: foraging activity of the butterflyfish Chaetodon striatus
      (Perciformes) in southeast Brazil.
AB  - The banded butterflyfish (Chaetodon striatus) from the tropical and subtropical
      western Atlantic is a territorial, diurnal forager on benthic invertebrates. It
      is usually seen moving singly or in pairs, a few meters above the sea floor. We
      studied the foraging activity of C. striatus on rocky reefs in southeastern
      Brazil. This fish spent about 11 h and 30 min per day on feeding activities, and
      preferred colonies of non-scleratinian anthozoans over sandy and rocky substrata
      while foraging. The lowest feeding rates were recorded in the early morning and
      late afternoon, but we found no further differences between feeding rates
      throughout the day. We also found no differences between the feeding rates of
      paired and single individuals.

PMID- 16097724
TI  - Malacological assessment and natural infestation of Biomphalaria straminea
      (Dunker, 1848) by Schistosoma mansoni (Sambon, 1907) And Chaetogaster limnaei (K.
      Von Baer, 1827) in an urban eutrophic watershed.
AB  - The objective of this study was to perform a malacological assessment at the
      Ibirite reservoir watershed in the metropolitan region of Belo Horizonte (Minas
      Gerais) and to evaluate the natural infestation rate of Biomphalaria straminea
      (Gastropoda: Planorbidae) by Schistosoma mansoni (Platyhelminthes: Trematoda) and
      Chaetogaster limnaei (Oligochaeta: Naididae). The samples were collected from
      July to August 2002. The B. straminea individuals collected were kept in the
      laboratory; the natural infestation rate by S. mansoni and C. limnaei was
      assessed weekly. The malacological assessment identified five mollusk species
      present in the Ibirite reservoir watershed: B. straminea, Physa marmorata, Lymnea
      sp., Melanoides tuberculatus, and Pomacea austrum. Laboratory observations showed
      that the B. straminea individuals were infected by C. limnaei rather than S.
      mansoni. Although there was no infection of B. straminea by S. mansoni, presence
      of B. straminea in itself merits close attention due to possible risk of human
      schistosomiasis by the local population.

PMID- 16097725
TI  - Biodiversity assessment of benthic macroinvertebrates along a reservoir cascade
      in the lower Sao Francisco river (northeastern Brazil).
AB  - In order to verify the cascade-system effect in benthic macroinvertebrate
      communities, and the implications for policy making and proposals for
      conservation and sustainable use of the lower portion of Sao Francisco river
      basin (Bahia State, Brazil), a three-reservoir cascade system including two
      stretches downstream were studied during dry (June, 1997) and rainy (March, 1998)
      periods. The dominant groups found were Mollusca (Melanoides tuberculata),
      Oligochaeta, and Chironomidae larvae. Low Shannon-Wiener and Pielou index values
      were found, but with no significant difference between the sampling periods.
      However, density and taxonomic richness were significantly different (t(0.05:
      31)) = -2.1945; p < 0.05; e t(0.05; 31) = -3.0600; p < 0.01) between the sampling
      periods, with a reduction in the number of taxa and macroinvertebrate abundance
      during the rainy period. An increasing gradient in benthic macroinvertebrate
      community structures was noted along the reservoir cascade from the first
      reservoir (Apolonio Sales), followed by a decrease downstream from the third
      reservoir of the system (Xing6). Despite the negative consequences of rapid
      proliferation of dams, which have caused widespread loss of freshwater habitats,
      the reservoir cascade system promoted an increase in benthic macroinvertebrate
      diversity, due to water-quality improvement along the system.

PMID- 16097726
TI  - Morphological changes of Sertoli cells during the male reproductive cycle of the
      teleost Piaractus mesopotamicus (Holmberg, 1887).
AB  - An investigation of the histological and ultrastructural changes of Sertoli cells
      during the male reproductive cycle in Piaractus mesopotamicus was made. The
      results showed that the Sertoli cell development is closely related with germ
      cell maturation. Therefore, these cells may have some role in germ cell
      maturation during the reproductive cycle of this species, whether in forming a
      tissue framework for the developing spermatogenic cysts, aiding in testes
      reorganization for a new reproductive cycle, in addition to other possible
      functions discussed in the text.

PMID- 16097727
TI  - Priority areas for anuran conservation using biogeographical data: a comparison
      of greedy, rarity, and simulated annealing algorithms to define reserve networks
      in cerrado.
AB  - Spatial patterns in biodiversity variation at a regional scale are rarely taken
      into account when a natural reserve is to be established, despite many available
      methods for determining them. In this paper, we used dimensions of occurrence of
      105 species of Anura (Amphibia) in the cerrado region of central Brazil to create
      a regional system of potential areas that preserves all regional diversity, using
      three different algorithms to establish reserve networks: "greedy", rarity, and
      simulated annealing algorithms. These generated networks based on complementarity
      with 10, 12, and 8 regions, respectively, widely distributed in the biome, and
      encompassing various Brazilian states. Although the purpose of these algorithms
      is to find a small number of regions for which all species are represented at
      least once, the results showed that 67.6%, 76.2%, and 69.5% of the species were
      represented in two or more regions in the three networks. Simulated annealing
      produced the smallest network, but it left out three species (one endemic). On
      the other hand, while the greedy algorithm produce a smaller solution, the rarity
      based algorithm ensured that more species were represented more than once, which
      can be advantageous because it takes into consideration the high levels of
      habitat loss in the cerrado. Although usually coarse, these macro-scale
      approaches can provide overall guidelines for conservation and are useful in
      determining the focus for more local and effective conservation efforts, which is
      especially important when dealing with a taxonomic group such as anurans, for
      which quick and drastic population declines have been reported throughout the
      world.

PMID- 16097728
TI  - Marsh deer (Blastocerus dichotomus) reintroduction in the Jatai Ecological
      Station (Luis Antonio, SP): spatial preferences.
AB  - Throughout the latter half of the twentieth century, wildlife habitat destruction
      and species extinctions have greatly increased. As the number of endangered
      species grows, the use of reintroduction as a conservation tool against species
      extinction increases. This study focuses on a 16-month study on marsh deer
      reintroduced in the Jatai Ecological Station. The animals were radio tagged and
      tracked daily between December 1998 and April 2000. Displacement activity and
      spatial preferences were monitored by triangulation. The animals wandered the
      floodplains inside the protected area and also a floodplain that is part of
      privately owned property on the western edge of the Jatai Ecological Station.
      During the study, most of the reintroduced marsh deer preferred the private
      floodplain area more than the floodplains inside the protected area. This
      preference revealed the ecological importance of the area and the necessity of
      its incorporation into the Jatai Ecological Station.

PMID- 16097729
TI  - Dynamics of extinction in coupled populations of the flour beetle Tribolium
      castaneum.
AB  - In this study we analyzed the effect of migration on the persistence time of
      coupled local populations of Tribolium in different environments. Four treatments
      were set up to compare different levels of environmental heterogeneity. We
      established high, low, moderate, and no heterogeneity. These levels were
      estimated by the different amounts of food offered to each population. To
      investigate how risk spreading works, a stochastic model for two subpopulations
      was employed. The high heterogeneity treatment resulted in the longest
      persistence, even though survival analysis revealed no significant difference
      among treatments. The magnitude of differences in growth rates among
      subpopulations is probably associated with persistence.

PMID- 16097730
TI  - Incubation and rearing-effort partitioning of wing-banded hornero Furnarius
      figulus (Passeriformes: Furnariidae).
AB  - We studied incubation and feeding rates in two of five broods in two oven nests
      of Furnarius figulus at Lagoa Rodrigo de Freitas. During incubation, the number
      of visits and time spent in the nest did not differ between the adults. The
      number of feeding visits was significantly different between members of the
      breeding pair of the first but not of the second nest. Nestlings received
      arthropods, fishes, and larvae in the first nest and, in the second, arthropods,
      larvae, and fruits. The nestlings stayed about 23 days in the nests.

PMID- 16097731
TI  - Effect of sub-lethal concentrations of permethrin on ovary activation in the
      predator Supputius cincticeps (Heteroptera: Pentatomidae).
AB  - Insecticides may cause mortality and deleterious effects on predatory stinkbugs.
      For this reason, the effect of five concentrations of permethrin applied on third
      instar nymphs of Supputius cincticeps (Stal) (Heteroptera: Pentatomidae) was
      investigated on ovary activation in this predator. The nymphs received topical
      application of permethrin in the following concentrations (mg a.i./ml): 10(-7),
      10(-6), 10(-5), 10(-4), and 10(-3). Ovary lengths and oocyte numbers were
      quantified following first egg mass. Ovary length of S. cincticeps varied from
      5.7 mm with 10(-4) mg a.i./ml, to 6.4 mm with 10(-7) mg a.i./ml, with similar
      values for the other permethrin concentrations and for the control. The number of
      oocytes per female varied from 13.5 with 10(-3) mg a.i./ml, to 29.2 for the
      control, with significant differences. The number of oocytes per female of nymphs
      exposed to a permethrin concentration of 10(-5) mg a.i./ml was similar to that of
      the control. However, the lower number of oocytes per female from nymphs exposed
      to other concentrations of permethrin suggests that this insecticide may affect
      the reproductive capacity of this predator. The results obtained are discussed in
      relation to tolerance of Heteroptera predators to insecticides and possible
      hormesis occurrence.

PMID- 16097732
TI  - Foraging on some nonfloral resources by stingless bees (Hymenoptera, Meliponini)
      in a Caatinga region.
AB  - In a caatinga region the flowers and nonfloral resources visited by highly
      eusocial bees, stingless beess and Apis mellifera (Africanized honey bee) were
      studied. During one year, monthly sampling took place in two sites at Serra da
      Capivara National Park (Piauf State, Brazil), one of them, including the local
      village, outside the park, and the other inside, using already existing park
      trails. With the help of entomological nets, all bees were caught while visiting
      floral and nonfloral resources. At the study sites we observed more stingless
      bees in nonfloral resources, made possible by human presence. Twelve stingless
      bee species used the nonfloral resources in different proportions, showing no
      preference for time of day, season of the year, or sites. During the rainy
      season, more water sources and abundant flowering plants were observed, which
      attract stingless bees, even though many worker bees were found foraging in the
      aqueous substrates while few were observed at water sources. This relationship
      was higher for stingless bee species than for Africanized honey bees. Paratrigona
      lineata was represented by few specimens in floral and nonfloral resources and is
      perhaps rare in this region. Frieseomelitta silvestrii could be considered rare
      in the floral resources, but they were abundant in nonfloral resources. The
      variety and intriguing abundance of bees in nonfloral resources suggests that
      these are an important part of the stingless bee niches, even if these resources
      are used for nest construction and defense.

PMID- 16097733
TI  - Preliminary notes on yeasts associated with necrotic cactus stems from different
      localities in Brazil.
AB  - The yeast species found in necrotic stems of three columnar cacti (Pilosocereus
      machrisii, Pilosocereus vilaboensis, and Praecereus euchlorus) at eight
      localities in Brazil were described and a similarity analysis using Sorensen
      distances was used to compare the composition of yeast species at these
      localities. Of 56 necrotic cactus stems sampled, 32 produced yeast colonies. Ten
      species of yeast or yeast-like microorganisms were identified from 53 isolates,
      with Pichia cactophila, Candida sonorensis, Geotrichum sp., and Sporopachydermia
      cereana being the most common. The remaining species occurred in low proportions
      in the cacti surveyed. The similarity analysis provided a dendogram (UPGMA) that
      clustered the yeast communities from different cactus species and indicated that
      host cactus species was unimportant in this clustering.

PMID- 16097734
TI  - Metabolic adjustments during semi-aestivation of the marble swamp eel
      (Synbranchus marmoratus, Bloch 1795)--a facultative air breathing fish.
AB  - Metabolic changes, principally in intermediary metabolism and nitrogen excretion,
      were investigated in the marble swamp eel (Synbranchus marmoratus) after 15 and
      45 days of artificially induced semi-aestivation. Glucose, glycogen, lactate,
      pyruvate, free amino acids, triglycerides, ammonia, urea, and urate contents were
      determined in liver, kidney, white muscle, heart, brain, and plasma. Lactate
      dehydrogenase, glutamate dehydrogenase, malate dehydrogenase, aspartate amino
      transferase, alanine amino transferase, glutamine synthase, ornithine carbamoyl
      transferase, and arginase enzymes were assayed. The teleost S. marmoratus
      maintained initial energetic demands by lipid oxidation. The course of normal
      oxidative processes was observed through tissue enzyme profiles. After the lipid
      stores were exhausted, the fish consumed body proteins. Constant values of
      hematocrit during induced semi-aestivation suggested that the water balance
      remained normal. Therefore, the surrounding water was probably did not trigger
      the semi-aestivation in this teleost. Decrease of ammonia and increase of renal
      urea synthesis after 45 days of semi-aestivation led to the assumption that an
      alternative form of eliminating ammonia exists. Metabolic changes entailed by
      starvation were proposed to explain the biosynthesis of small molecules involved
      in the semi-aestivation of S. marmoratus.

PMID- 16097735
TI  - The nutritional status of zooplankton in a tropical reservoir: effects of food
      quality and community structure.
AB  - The temporal variability of energetic reserves of zooplankton in the eutrophic
      Pampulha reservoir was investigated during two successive annual cycles. The
      effects of dominance of large filter-feeding cladocerans (Daphnia) and the
      occurrence of massive blooms of the cyanobacteria Microcystis on the energetic
      reserves of zooplankton were tested. This study showed that phytoplankton
      composition has a greater effect on energetic reserves of zooplankton. Some
      associations between lipid levels and the specific composition of zooplankton
      were also found. This study also demonstrated that the elementary composition of
      phosphorus in zooplankton can be used as an estimator of the nutritional status
      of zooplankton.

PMID- 16097736
TI  - Effects of eutrophication on size and biomass of crustacean zooplankton in a
      tropical reservoir.
AB  - This is a long-term study (1993-1998) on the effects of increasing eutrophication
      on the crustacean zooplankton structure in a eutrophic reservoir. The study first
      demonstrates that the eutrophication increase verified is a phenomenon well
      described by a single abiotic variable: total phosphorus. During the study
      period, zooplankton suffered extensive qualitative and quantitative changes.
      Significant size and biomass responses of certain zooplankton groups to the
      temporal variations of total phosphorus were found. These findings suggest that
      the variables size and biomass of major zooplankton groups should always be
      considered simultaneously in order to assess impacts caused by eutrophication on
      the structure of zooplankton.

PMID- 16097737
TI  - Extensive consumption of Tabebuia aurea (Manso) Benth. & Hook. (Bignoniaceae)
      nectar by parrots in a Tecoma savanna in the southern Pantanal (Brazil).
AB  - Neotropical parrots forage for various food items such as seeds, fruit pulp,
      flowers, young leaves, and even arthropods. While foraging, many species wander
      over large areas that include both open and closed habitats. In this study, I
      examined parrot foraging activity during a brief synchronous and massive
      flowering in August 1998 in a tecoma savanna (dominated by Tabebuia aurea) in the
      southern Pantanal. Six parrot species, ranging from the small Brotogeris chiriri
      to the large Amazona aestiva, foraged for T. aurea nectar, but Nandayus nenday
      was by far the major nectar consumer, and the results of each of their visits,
      like those of the other species, was damage of a substantial proportion of the
      existing flower crop. Parrots foraged mostly during the afternoon, when nectar
      concentration tended to be higher. Nevertheless, compared to bird-pollinated
      flowers, which produce copious nectar, T. aurea had a smaller mean nectar volume
      per flower. Hence, presumably the amount of damage wreaked by these parrots
      resulted from their efforts to obtain part of their daily energy and water
      requirements. Thus, the synchronous and massive flowering occurring in such a
      brief period in the dry season may be related to, among other factors, the
      necessity of satiating predators such as parrots, which are still abundant in the
      Pantanal.

PMID- 16097738
TI  - Oyster condition index in Crassostrea rhizophorae (Guilding 1828) from a heavy
      metal polluted coastal lagoon.
AB  - The condition index (CI) of oysters represents an ecophysiological approach to
      estimate meat quality and yield in cultured bivalve mollusks. In the present
      study, the CI of oysters from a heavy-metal polluted bay was analyzed with
      respect to Zn and Cd contamination in soft tissues, spawning, and polychaete
      infestation. The CI was calculated through a new technique based on molds made to
      measure the volume of oyster-shell internal cavities. The higher CI values (over
      9 in the dry season) were probably related availability of suspended particles
      rich in organic matter in the bay, while the rapid reduction in the CI from one
      season to the next at some stations suggests the effect of spawning. Polychaete
      infestation was considered low (18.7%) and produced no clear CI effects. The Cd
      in the oyster tissue collected during the rainy season was weak, although still
      significantly correlated with the CI (r = -0.36; p < 0.05). All other comparisons
      of CI and metal concentrations demonstrated a non-significant correlation. The CI
      variations observed on the temporal and spatial scale were likely to have been
      caused by availability of organic matter and spawning, rather than spionid
      infestation or metal body burdens.

PMID- 16097739
TI  - Evidence indicating participation of the serotonergic system in controlling
      feeding behavior in Coturnix japonica (Galliformes: Aves).
AB  - We investigated participation of the brain serotonergic system in food intake
      control by using oral and systemic administration of serotonin precursors in
      quails (Coturnix japonica). Dietary supplemental tryptophan (0.1-50.0 g/kg)
      provoked a dose-dependent inhibition of food intake during a 5-h observation
      period, which persisted up to 24 h for doses of 30.0 and 50.0 g/kg. Normally fed
      and fasted animals treated with hydroxytryptophan (12.5-50.0 mg/kg) by the
      intracoelomic route showed an acute inhibition of food intake. Hypophagia in
      fasted birds was only effective when the precursor was administered immediately
      before food presentation. A similar response was obtained by administering
      serotonin (0.125-2.5 mg/kg, sc), with animals showing a hypnogenic response
      within the first ten minutes after administration, suggesting that, in contrast
      to mammals, the amine crosses the blood-brain barrier in quails. Administration
      of hydroxytryptophan at all doses tested induced significant dipsogenic behavior
      despite the concomitant hypnogenic response. The results suggest the involvement
      of serotonergic pathways in food intake control in quails and also show, for the
      first time, hypnogenic action induced by serotonin and a hyperdipsic effect
      elicited by hydroxytryptophan.

PMID- 16097740
TI  - Growth and mortality of black bass, Micropterus salmoides (Pisces, Centrachidae;
      Lacapede, 1802) in a reservoir in southern Brazil.
AB  - The black bass, Micropterus salmoides, was introduced to Brazil from North
      America in 1922. Since then the species has been reared in aquaculture facilities
      intended to stock reservoirs as additions to native stocks available for angling.
      At present no scientific information on the biology of black bass in Brazilian
      waters is available. Since black bass dispersion may cause severe impacts on
      native Brazilian fish fauna, information on the basic biological parameters of
      this species is necessary. The objective of the present study is to provide
      information on the growth, age structure, and mortality of the species in a small
      reservoir in southern Brazil, where the species reproduces regularly. Based on
      scale readings, the von Bertalanffy growth curve was calculated and compared to
      the length-frequency distribution of the population. Both methods showed similar
      results. Maximum length was about 44 cm. The mean length at the end of the first
      year was 23.1 cm (s.d. = 13.88); at that of the second, 37.3 cm (s.d. = 12.52);
      and 41.4 cm (s.d. = 9.92) at the third. Oldest fish were three years old. The
      growth performance index phi' was 3.28 cm year(-1). Mortality increased from 0.16
      year(-1) between the first and the second cohort, to 0.8 year(-1) between the
      second and third. The results show that black bass in Brazil grows faster than in
      its area of origin, but longevity is shorter and body shape, stouter. The cause
      of high mortality at a relatively early age may be connected with the loss of
      genetic diversity due to inbreeding of the Brazilian stocks, which originated
      from few introduced individuals a long time ago. The fact that black bass
      reproduces in reservoirs and grows rapidly may be considered a threat to
      conserving fish diversity in Brazilian ecosystems.

PMID- 16097741
TI  - Characterization of Adenosine deaminase (ADA) in hemolymph of Biomphalaria
      glabrata.
AB  - Adenosine is an important signaling molecule for many cellular events. Adenosine
      deaminase (ADA) is a key enzyme for the control of extra- and intra-cellular
      levels of adenosine. Activity of ADA was detected in hemolymph of B. glabrata and
      its optimum assay conditions were determined experimentally. The pH variation
      from 6.2 to 7.8 caused no significant change in ADA activity. Using adenosine as
      a substrate, the apparent Km at pH 6.8 was 734 micromols.L(-1). Highest activity
      was found at 37 degrees C. Standard assay conditions were established as being 15
      minutes of incubation time, 0.4 microL of pure hemolymph per assay, pH 6.8, and
      37 degrees C. This enzyme showed activities of 834 +/- 67 micromol.min(-1).L(-1)
      (25 degrees C) and 2029 +/- 74 micromol.min(-1).L(-1) (37 degrees C), exceeding
      those in healthy human serum by 40 and 100 times, respectively. Higher incubation
      temperature caused a decrease in activity of 20% at 43 degres C or 70% at 50
      degrees C for 15 minutes. The ADA lost from 26% to 78% of its activity when
      hemolymph was pre-incubated at 50 degrees C for 2 or 15 minutes, respectively.
      Since the ADA from hemolymph presented high levels, it can be concluded that in
      healthy and fed animals, adenosine is maintained at low concentrations. In
      addition, the small variation in activity over the 6.2 to 7.8 range of pH
      suggests that adenosine is maintained at low levels in hemolymph even under
      adverse conditions, in which the pH is altered.

PMID- 16097742
TI  - Rapidly prototyped three-dimensional nanofluidic channel networks in glass
      substrates.
AB  - Microfluidic and nanofluidic technologies have long sought a fast, reliable
      method to overcome the creative limitations of planar fabrication methods, the
      resolution limits of lithography, and the materials limitations for fast
      prototyping. In the present work, we demonstrate direct 3D machining of
      submicrometer diameter, subsurface fluidic channels in glass, via optical
      breakdown near critical intensity, using a femtosecond pulsed laser. No
      postexposure etching or bonding is required; the channel network (or almost any
      arbitrary-shaped cavity below the surface) is produced directly from "art-to
      part". The key to this approach is to use very low energy, highly focused, pulses
      in the presence of liquid. Microbubbles that result from laser energy deposition
      gently expand and extrude machining debris from the channels. These bubbles are
      in a highly damped, low Reynolds number regime, implying that surface spalling
      due to bubble collapse is unimportant. We demonstrate rapid prototyping of three
      dimensional "jumpers", mixers, and other key components of complex 3D microscale
      analysis systems in glass substrates.

PMID- 16097743
TI  - Catalytic three-dimensional protein architectures.
AB  - We demonstrate a strategy for microfabricating catalytically active, three
      dimensional matrixes composed of cross-linked protein in cellular and
      microfluidic environments. In this approach, a pulsed femtosecond laser is used
      to excite photosensitizers via multiphoton absorption within three-dimensionally
      defined volumes, a process that promotes cross-linking of protein residue side
      chains in the vicinity of the laser focal point. In this manner, it is possible
      to fabricate protein microparticles with dimensions on the order of the
      multiphoton focal volume (less than 1 microm(3)) or, by scanning the position of
      a laser focal point relative to a specimen, to generate surface-adherent matrixes
      or cables that extend through solution for hundreds of micrometers. We show that
      protein matrixes can be functionalized either through direct cross-linking of
      enzymes, by decoration of avidin matrixes with biotinylated enzymes, or by cross
      linking biotinylated proteins that then are linked to biotinylated enzymes via an
      avidin couple. Several formats are explored, including microparticles that can be
      translocated to desired sites of action (including cytosolic positions), protein
      pads that generate product gradients within cell cultures, and on-column
      nanoreactors for microfluidic systems. These biomaterial fabrication technologies
      offer opportunities for studying a variety of cell functions, ranging from single
      cell biochemistry and development to perturbation and analysis of small
      populations of cultured cells.

PMID- 16097744
TI  - Enzymatically amplified surface plasmon resonance imaging detection of DNA by
      exonuclease III digestion of DNA microarrays.
AB  - This paper describes a novel approach utilizing the enzyme exonuclease III in
      conjunction with 3'-terminated DNA microarrays for the amplified detection of
      single-stranded DNA (ssDNA) with surface plasmon resonance (SPR) imaging. When
      ExoIII and target DNA are simultaneously introduced to a 3'-terminated ssDNA
      microarray, hybridization adsorption of the target ssDNA leads to the direction
      dependent ExoIII hydrolysis of probe ssDNA strands and the release of the intact
      target ssDNA back into the solution. Readsorption of the target ssDNA to another
      probe creates a repeated hydrolysis process that results over time in a
      significant negative change in SPR imaging signal. Experiments are presented that
      demonstrate the direction-dependent surface enzyme reaction of ExoIII with double
      stranded DNA as well as this new enzymatically amplified SPR imaging process with
      a 16-mer target ssDNA detection limit of 10-100 pM. This is a 10(2)-10(3)
      improvement on previously reported measurements of SPR imaging detection of ssDNA
      based solely on hybridization adsorption without enzymatic amplification.

PMID- 16097745
TI  - Unambiguous assignment of intramolecular chemical cross-links in modified
      mammalian membrane proteins by Fourier transform-tandem mass spectrometry.
AB  - Fourier transform tandem mass spectrometry (FT-MS/MS) can be used to
      unambiguously assign intramolecular chemical cross-links to specific amino acid
      residues even when two or more possible cross-linking sites are adjacent in the
      cross-linked protein. Bovine rhodopsin (Rho) in its dark-adapted state was
      intramolecularly cross-linked with lysine-cysteine (K-C) or lysine-lysine (K-K)
      cross-linkers to obtain interatomic distance information. Large, multiply
      charged, cross-linked peptide ions containing adjacent lysines, corresponding to
      Rho(50-86) (K(66) or K(67)) cross-linked to Rho(310-317) (C(316)) or Rho(318-348)
      (K(325) or K(339)), were fragmented by collision-induced dissociation (CID),
      infrared multiphoton dissociation (IRMPD), and electron capture dissociation
      (ECD). Complementary sequence-specific information was obtained by combining
      cross-link assignments; however, only ECD revealed full palmitoylation of
      adjacent cysteines (C(322) and C(323)) and cross-linking of K(67) (and not K(66))
      to C(316), K(325), and K(339). ECD spectra contained crucial c- and z-ions
      resulting from cleavage of the bond between K(66) and K(67). To our knowledge,
      this work also presents the first demonstration that ECD can be used to
      characterize S-linked fatty acid acylation on cysteines. The comprehensive
      fragmentation of large peptides by CID, IRMPD, and particularly ECD, in
      conjunction with the high resolution and mass accuracy of FT-MS/MS, is shown to
      be a valuable means of characterizing mammalian membrane proteins with both
      chemical and posttranslational modifications.

PMID- 16097746
TI  - Label-free electrochemical detection for aptamer-based array electrodes.
AB  - An electrochemical impedance spectroscopy method of detection for aptamer-based
      array electrodes is reported in which the binding of aptamers immobilized on gold
      electrodes leads to impedance changes associated with target protein binding
      events. Human IgE was used as a model target protein and incubated with the
      aptamer-based array consisting of single-stranded DNA containing a hairpin loop.
      To increase the binding efficiency for proteins, a hybrid modified layer
      containing aptamers and cysteamine was fabricated on the photolithographic gold
      surface through molecular self-assembly. Atomic force microscopy analysis
      demonstrated that human IgE could be specifically captured by the aptamer and
      stand well above the self-assembled monolayer (SAM) surface. Compared to
      immunosensing methods using anti-human IgE antibody as the recognition element,
      impedance spectroscopy detection could provide higher sensitivity and better
      selectivity for aptamer-modified electrodes. The results of this method show good
      correlation for human IgE in the range of 2.5-100 nM. A detection limit of 0.1 nM
      (5 fmol in a 50-microL sample) was obtained, and an average of the relative
      standard deviation was <10%. The method herein describes the first label-free
      detection for arrayed electrodes utilizing electrochemical impedance
      spectroscopy.

PMID- 16097747
TI  - Sample handling for mass spectrometric proteomic investigations of human sera.
AB  - Proteomic investigations of sera are potentially of value for diagnosis,
      prognosis, choice of therapy, and disease activity assessment by virtue of
      discovering new biomarkers and biomarker patterns. Much debate focuses on the
      biological relevance and the need for identification of such biomarkers while
      less effort has been invested in devising standard procedures for sample
      preparation and storage in relation to model building based on complex sets of
      mass spectrometric (MS) data. Thus, development of standardized methods for
      collection and storage of patient samples together with standards for
      transportation and handling of samples are needed. This requires knowledge about
      how sample processing affects MS-based proteome analyses and thereby how
      nonbiological biased classification errors are avoided. In this study, we
      characterize the effects of sample handling, including clotting conditions,
      storage temperature, storage time, and freeze/thaw cycles, on MS-based proteomics
      of human serum by using principal components analysis, support vector machine
      learning, and clustering methods based on genetic algorithms as class modeling
      and prediction methods. Using spiking to artificially create differentiable
      sample groups, this integrated approach yields data that--even when working with
      sample groups that differ more than may be expected in biological studies-
      clearly demonstrate the need for comparable sampling conditions for samples used
      for modeling and for the samples that are going into the test set group. Also,
      the study emphasizes the difference between class prediction and class comparison
      studies as well as the advantages and disadvantages of different modeling
      methods.

PMID- 16097748
TI  - Atomic absorption spectroscopy for mercury, automated by sequential injection and
      miniaturized in lab-on-valve system.
AB  - Sodium borohydride-based hydride generation was automated by using programmable
      flow within the lab-on-valve module. Mercury vapor, generated in the reaction
      mixture, was extracted in a gas/liquid separator. The gas-expansion separator was
      miniaturized and compared with the performance of a novel gas separator that
      exploits the combination of Venturi effect and reduced pressure. Cold vapor
      atomic spectroscopy was used as a model system, with detection of mercury by
      absorption at 254 nm and limit of detection of 9 microg of Hg/L, using 300 microL
      of sample and 100 microL of borohydride. This work introduces, for the first
      time, sequential injection technique for hydride generation, highlights
      advantages of using programmable flow, and outlines means for miniaturization of
      assays based on spectroscopy of volatile species.

PMID- 16097749
TI  - Real-time PCR measurement by fluorescence anisotropy.
AB  - We have developed an instrument for monitoring real-time PCR using fluorescence
      anisotropy, enabling an assay chemistry in which the fluorescence from a labeled
      primer elucidates amplification. The instrument holds the sample temperature
      constant to within +/-0.03 degrees C during measurement in the extension phase of
      each PCR cycle and achieves 0.116 mP FA resolution. Primer conjugation with Alexa
      Fluor 488, when compared with other fluorophores, is shown to provide the
      greatest FA range between primer and product. Comparable reproducibility and
      linearity of the crossing point for a range of target copy numbers is observed
      between the FA-based assay run in our instrument and the SYBR green assay run in
      commercial instrumentation. Reproducibility is also consistent with Poisson
      distributed experimental error in aliquoting starting copies, a theoretical limit
      to instrument/assay performance.

PMID- 16097750
TI  - Time-dependent study of the exfoliation process of carbon nanotubes in aqueous
      dispersions by using UV-visible spectroscopy.
AB  - In this paper we demonstrate that the sonication-driven exfoliation of aggregates
      and bundles of single-wall carbon nanotubes (SWNTs) in an aqueous surfactant
      solution can be easily monitored by UV-vis spectroscopy. The different stages of
      the exfoliation process were directly visualized by cryogenic temperature
      transmission electron microscopy, showing an excellent correspondence with the
      spectroscopic data: the maximum achievable exfoliation (which does not mean that
      100% of the NTs are effectively exfoliated) corresponds to the maximum UV-vis
      absorbance of the NT solution. Moreover, it has been observed that NTs produced
      by the arc-discharge technology (Carbolex NTs) require less energy to achieve
      maximum exfoliation than NTs produced by chemical vapor deposition (HiPCO NTs).
      This difference is attributed to weaker van der Waals attraction between Carbolex
      NTs in the bundles and aggregates.

PMID- 16097751
TI  - Recognition of dengue virus protein using epitope-mediated molecularly imprinted
      film.
AB  - Molecularly imprinted film was fabricated in the presence of a pentadecapeptide
      onto a quartz crystal microbalance (QCM) chip. This 15-mer peptide has been known
      as the linear epitope of the dengue virus NS1 protein. Imprinting resulted in an
      increased polymer affinity toward the corresponding templates but also to the
      virus protein. Direct detection of the dengue virus protein was achieved
      quantitatively. The QCM chip response to the NS1 protein was obtained using
      epitope-mediated imprinting demonstrating a comparable frequency shift in chips
      immobilized with monoclonal antibodies. The binding effect was further enhanced
      and confirmed using a monoclonal antibody to form a sandwich with the MIP-NS1
      protein complex on the chip. No pretreatment was required.

PMID- 16097752
TI  - Specificity of immobilized metal affinity-based IMAC/C18 tip enrichment of
      phosphopeptides for protein phosphorylation analysis.
AB  - We have developed a simple, highly specific enrichment procedure for
      phosphopeptides, by increasing the specificity of an immobilized metal affinity
      column (IMAC) without using any chemical reaction. The method employs a biphasic
      IMAC-C18 tip, in which IMAC beads are packed on an Empore C18 disk in a 200
      microL pipet tip. Phosphopeptides are separated from non-phosphopeptides on the
      IMAC in an optimized solvent without any chemical reaction, then desorbed from
      the IMAC using a phosphate buffer, reconcentrated, and desalted on the C18 disk.
      The increase in selectivity was achieved by (a) using a strong acid to
      discriminate phosphates from carboxyl groups of peptides and (b) using a high
      concentration of acetonitrile to remove hydrophobic non-phosphopeptides. The
      entire procedure was optimized by using known phosphoproteins such as Akt1 kinase
      and protein kinase A. Although it was difficult to detect phosphopeptides in
      MALDI-MS spectra of tryptic peptide mixtures before enrichment, after the IMAC
      procedure, we could successfully detect phosphopeptides with almost no non
      phosphopeptides. Next, we constructed an array of IMAC-IMAC/C18 tips, such that
      number of arrayed tips on a 96-well plate could easily be changed depending on
      the loading amount of sample. Applying this approach to mouse forebrain resulted
      in the identification of 162 phosphopeptides (166 phosphorylation sites) from 135
      proteins using nano-LC/MS.

PMID- 16097753
TI  - Peptide nanotube-modified electrodes for enzyme-biosensor applications.
AB  - The fabrication and notably improved performance of composite electrodes based on
      modified self-assembled diphenylalanine peptide nanotubes is described. Peptide
      nanotubes were attached to gold electrodes, and we studied the resulting
      electrochemical behavior using cyclic voltammetry and chronoamperometry. The
      peptide nanotube-based electrodes demonstrated a direct and unmediated response
      to hydrogen peroxide and NADH at a potential of +0.4 V (vs SCE). This biosensor
      enables a sensitive determination of glucose by monitoring the hydrogen peroxide
      produced by an enzymatic reaction between the glucose oxidase attached to the
      peptide nanotubes and glucose. In addition, the marked electrocatalytic activity
      toward NADH enabled a sensitive detection of ethanol using ethanol dehydrogenase
      and NAD+. The peptide nanotube-based amperometric biosensor provides a potential
      new tool for sensitive biosensors and biomolecular diagnostics.

PMID- 16097754
TI  - Integrated light collimating system for extended optical-path-length absorbance
      detection in microchip-based capillary electrophoresis.
AB  - We have developed an integrated light collimating system with a microlens and a
      pair of slits for extended optical path length absorbance detection in a
      capillary electrophoresis (CE) microchip. The collimating system is made of the
      same material as the chip, poly(dimethylsiloxane) (PDMS), and it is integrated
      into the chip during the molding of the CE microchannels. In this microchip, the
      centers of an extended 500-microm detection cell and two optical fibers are self
      aligned, and a planoconvex microlens (r = 50 microm) for light collimation is
      placed in front of a light-delivering fiber. To block stray light, two
      rectangular apertures, realized by a specially designed three-dimensional
      microchannel, are made on each end of the detection cell. In comparison to
      conventional extended detection cell having no collimator, the percentage of
      stray radiation readout fraction in the collimator integrated detection cell is
      significantly reduced from 31.6 to 3.8%. The effective optical path length is
      increased from 324 to 460 microm in the collimator integrated detection cell. The
      detection sensitivity is increased by 10 times in the newly developed absorbance
      detection cell as compared to an unextended, 50-microm-long detection cell. The
      concentration detection limit (S/N = 3) for fluorescein in the collimator
      integrated detection cell is 1.2 microM at the absorbance detection limit of
      0.001 AU.

PMID- 16097755
TI  - Thermoplastic elastomer gels: an advanced substrate for microfluidic chemical
      analysis systems.
AB  - We demonstrate the use of thermoplastic elastomer gels as advanced substrates for
      construction of complex microfluidic networks suitable for use in miniaturized
      chemical analysis systems. These gels are synthesized by combining inexpensive
      polystyrene-(polyethylene/polybutylene)-polystyrene triblock copolymers with a
      hydrocarbon extender oil for which the ethylene/butylene midblocks are
      selectively miscible. The insoluble styrene end blocks phase separate into
      localized nanodomains, resulting in the formation of an optically transparent,
      viscoelastic, and biocompatible gel network that is melt-processable at
      temperatures in the vicinity of 100 degrees C. This unique combination of
      properties allows microfluidic channels to be fabricated in a matter of minutes
      by simply making impressions of the negative relief structures on heated master
      molds. Melt processability allows multiple impressions to be made against
      different masters to construct complex geometries incorporating multi-height
      features within the same microchannel. Intricate interconnected multilayered
      structures are also easily fabricated owing to the ability to bond and seal
      multiple layers by briefly heating the material at the bond interface. Thermal
      and mechanical properties are tunable over a wide range through proper selection
      of gel composition.

PMID- 16097756
TI  - Effect of change in angle between microelectrode surface and jet direction in
      flow system on current response in solutions of different ionic strength.
AB  - The influence of stream orientation versus surface of microelectrode detector was
      examined in the range between vertical and parallel flow for various jet
      velocities and various levels of supporting electrolyte. The flow cell was
      equipped with a conical body Pt microdisk electrode, and the measurements
      involved voltammetry and chronoamperometry. Ferrocene, two its charged
      derivatives (sodium ferrocenylo sulfate and ferrocenylomethyltrimethylamino
      hexafluorophosphate) and sodium iodide were employed as the substrates in the
      experiments. The strongest convectional transport and the highest signal of the
      analytes was obtained for alpha = 60 degrees (alpha is the angle between the
      electrode surface and the stream direction). The measured current increased by up
      to 1.85 times versus the traditional setup, and therefore, this new geometry of
      the detector is analytically advantageous. The value of alpha corresponding to
      the highest signal tended to decrease to approximately 45 degrees in the absence
      of supporting electrolyte provided that either flow rate or analyte concentration
      was above a certain threshold value. The experiments indicated that the interplay
      of the convectional and migrational components in the analyte transport is
      different for the charge increase and the charge cancellation processes. These
      experimental facts were confirmed by digital simulation results.

PMID- 16097757
TI  - Scanning electrochemical microscopy. 55. Fabrication and characterization of
      micropipet probes.
AB  - The fabrication and characterization of novel micropipet probes for use in
      scanning electrochemical microscopy (SECM) are described. These can be used to
      dispense small (pL) amounts of a solution while monitoring the electrochemical
      response at a substrate and at a ring electrode tip on the micropipet probe. The
      probes were constructed by insulating gold-coated borosilicate micropipets with
      electrophoretic paint and exposing a ring electrode at the tip by heat treatment.
      Characterization of the probes was performed using scanning electron microscopy,
      cyclic voltammetry, and SECM approach curve experiments. Routine construction of
      tips with diameters of the order of 3 microm was possible using this technique.
      The probes exhibited stable steady-state currents and positive and negative
      feedback approach curves that agreed with those predicted by theory.
      Demonstrative SECM imaging experiments were performed using a picodispenser to
      continuously dispense an electroactive solution (ferrocenemethanol) to the SECM
      cell while the probe was located within a few micrometers of a Pt substrate
      surface. Oxidation of the dispensed electroactive solution was performed at the
      substrate, and feedback currents were measured at the probe tip by holding the
      gold ring at a reducing potential. This mode of tip-dispensing SECM was used to
      obtain images of a platinum substrate electrode while monitoring both the
      substrate current and the feedback current at the probe.

PMID- 16097758
TI  - Electrical detection of DNA hybridization based on enzymatic accumulation
      confined in nanodroplets.
AB  - Electrical monitoring of DNA hybridization is one way to reduce the cost and size
      of the DNA chip reader in comparison with the more classical optical detection.
      Within electrical methods, electrochemical detection shows very high performances
      in terms of accuracy and sensitivity, especially when an enzymatic accumulation
      is used to amplify the signal. However, signal multiplexing for miniaturized
      systems based on both enzymatic accumulation and electrochemical detection
      remains challenging due to the Brownian diffusion of the detected product of the
      enzymatic reaction. We present here a DNA chip with electrical detection based on
      the following sequence: (i) hybridization of nucleic acids and washing in a
      liquid layer as usual, (ii) formation of independent nanodroplets on each
      detection site, (iii) enzymatic accumulation in each droplet avoiding cross
      contamination between neighboring sites, and (iv) electrochemical detection of
      the product accumulated during the enzymatic reaction. The simple and fast
      transition from the liquid layer (hybridization step) to an array of nanodroplets
      (enzymatic accumulation and detection steps) was performed through the filling of
      the hybridization chamber with a solution containing the enzymatic substrates,
      the drawing of this solution, and the simultaneous creation of droplets thanks to
      retention areas based on circular rims or hydrophilic rings. Using this approach,
      hybridization is achieved in a liquid layer as usual, followed by the enzymatic
      accumulation in nanodroplets to avoid the cross-talk between neighboring sites.
      Moreover, working in droplets enables a fast increase in the concentration of the
      product generated by the enzymatic reaction and thus an improvement of the
      detection limit of the system.

PMID- 16097759
TI  - Analyzing the mechanisms of selectivity in biomimetic self-assemblies via IR and
      NMR spectroscopy of prepolymerization solutions and molecular dynamics
      simulations.
AB  - Molecularly imprinted polymers (MIPs) for 2,4-dichlorophenoxyacetic acid were
      synthesized via a noncovalent approach with 4-vinylpyridine as functional monomer
      and ethylene glycol dimethacrylate as cross-linker in a methanol/water mixture.
      Templated polymers synthesized in this self-assembly approach rely on complex
      formation between the target analyte and functional monomers in porogenic
      solution prior to radical polymerization. Consequently, the achievable
      selectivity is governed by the nature and stability of these complexes. The
      nature of noncovalent interactions responsible for complex formation during
      imprinting of the template 2,4-dichlorophenoxyacetic acid (2,4-D) with the
      functional monomer 4-vinylpyridine has been investigated. Fourier transform
      infrared and 1H NMR spectroscopies provide the fundamental analytical basis for
      rationalizing the mechanisms of recognition during the imprinting process probing
      the governing interactions for selective binding site formation at a molecular
      level. Molecular modeling studies in explicit solvent (chloroform and water)
      corroborate the importance of hydrogen bonding in aprotic solvents and of
      hydrophobic interactions in protic media in agreement with the experimental
      spectroscopic investigations of prepolymerization solutions. Furthermore,
      chromatographic studies of the synthesized MIPs provided insight on the
      importance of size, shape, and functionality during selective 2,4-D rebinding
      processes confirming the results obtained during the prepolymerization studies.

PMID- 16097760
TI  - Reversible resistance modulation in mesoscopic silver wires induced by exposure
      to amine vapor.
AB  - Ensembles of silver nanowires (AgNEs) with diameters ranging from 200 nm to 1.0
      microm have been prepared by electrochemical step edge decoration. These AgNEs
      showed a rapid (< 5 s), reversible increase in resistance upon exposure to the
      vapor of ammonia, trimethylamine, and pyridine. The amplitude of the resistance
      change was up to +3000% (DeltaR/Ro)-more than 2 orders of magnitude larger than
      can be explained based on boundary layer scattering effects. We experimentally
      probe the mechanism for this resistance modulation in the case of ammonia, and we
      propose a model to describe it. Conductive tip atomic force microscopy was used
      to probe individual sections of nanowires in AgNEs; these data revealed that the
      resistance change caused by NH(3) exposure was concentrated within a minority
      (approximately 10%) of the 5-microm wire segments that were probed--not uniformly
      distributed along each nanowire. All AgNEs showed a temperature dependence of
      their resistance, alpha, that was smaller than expected for silver metal. Highly
      sensitive AgNEs sometimes showed a negative alpha, characteristic of
      semiconductors, but negative alpha values were never observed for AgNEs with a
      low sensitivity to NH3. AgNEs did not respond to hydrocarbons, O2, H2O, N2, CO,
      or Ar, but a large (DeltaR/Ro > |-50%|) irreversible decrease in resistance was
      seen upon exposures to acids including HCl, HNO3, and H2SO4. Based on these and
      other data, we propose a model in which oxidized constrictions in silver
      nanowires limit the conductivity of the wire and provide a means for "gating"
      conduction based on the protonation state of the oxide surface.

PMID- 16097761
TI  - Measurement of ion swarm distribution functions in miniature low-temperature co
      fired ceramic ion mobility spectrometer drift tubes.
AB  - Measurements of the performance of a miniature, portable 12-mm-diameter, 57-mm
      length low-temperature cofired ceramic (LTCC) ion mobility spectrometer drift
      tube were undertaken to verify models of ion transport and determine the physical
      shape of the ion "swarms" in the LTCC tube. Simplified two-dimensional Gaussian
      models of ion swarm shape were fit to measured data to extract geometrical shape
      parameters. Results indicate that tube-transfer function effects that produce
      asymmetric ion swarms are minimized in the tube reducing temporal dispersion.
      Data are presented that illustrate the swarm shape as a function of gate time,
      electric field magnitude, and total charge in the ion swarm. Characterization and
      understanding of the ion transport mechanisms and effects that limit the
      resolution and other performance parameters of miniature IMS drift tubes is
      essential to the development of practical, robust, portable systems for "first
      responder" and homeland security missions.

PMID- 16097762
TI  - Response characteristics of a reversible electrochemical sensor for the polyion
      protamine.
AB  - We describe here in detail the first reversible electrochemical sensors for the
      polyion protamine. Potentiometric sensors were proposed in recent years, mainly
      for the determination of the polyions heparin and protamine. Such potentiometric
      polyion sensors functioned on the nonequilibrium extraction of polyions into a
      hydrophobic membrane phase via ion pairing with lipophilic ion exchangers. This
      made it difficult to design sensors that operate in a truly reversible fashion.
      The reversible sensors described here utilize the same basic response mechanism
      as their potentiometric counterparts, but the processes of extraction and ion
      stripping are now fully controlled electrochemically. Spontaneous polyion
      extraction is avoided by using membranes containing highly lipophilic
      electrolytes that possess no ion-exchange properties. Reversible extraction of
      polyions is induced if a constant current pulse of fixed duration is applied
      across the membrane, followed by a baseline potential pulse. The key theoretical
      response principles of this new class of polyion sensors are discussed here and
      compared to those of its classical potentiometric counterpart. The
      electrochemical sensing system is characterized in terms of optimal working
      conditions, membrane composition, selectivity, and influence of sample stirring
      and organic-phase diffusion coefficient on the response characteristics.
      Excellent potential stability and reversibility of the sensors are observed, and
      measurements of heparin concentration in whole blood samples via protamine
      titration are demonstrated.

PMID- 16097763
TI  - Typing of multiple single-nucleotide polymorphisms using ribonuclease cleavage of
      DNA/RNA chimeric single-base extension primers and detection by MALDI-TOF mass
      spectrometry.
AB  - A novel single-base extension (SBE) assay using cleavable and noncleavable SBE
      primers in the same reaction mix is described. The cleavable SBE primers
      consisted of deoxyribonucleotides and one ribonucleotide (hereafter denoted
      chimeric primers), whereas the noncleavable SBE primers consisted of only
      deoxyribonucleotides (hereafter denoted standard primers). Biotin-labeled ddNTPs
      were used in the SBE reaction, and the SBE products were purified using the
      monomeric avidin triethylamine purification protocol, ensuring that only primers
      extended with a biotin-ddNTP in the 3'-end were isolated. A ribonuclease mix was
      developed to specifically cleave the chimeric primers, irrespective of the base
      of the ribonucleotide, whereas standard primers without a ribonucleotide were
      unaffected by the ribonuclease treatment. The SBE products were analyzed in
      linear mode using a matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometer. The cleaved SBE products were detected in the 2000-5500 m/z
      range, and the noncleaved SBE products were detected in the 5500-10 000 m/z
      range. The method was validated by typing 17 Y chromosome single-nucleotide
      polymorphisms in 100 males with a 17-plex SBE package containing 9 chimeric
      primers and 8 standard primers.

PMID- 16097764
TI  - Selective detection of a catecholamine against electroactive interferents using
      an interdigitated heteroarray electrode consisting of a metal oxide electrode and
      a metal band electrode.
AB  - We developed an interdigitated array electrode (IDAE) consisting of a metal oxide
      electrode and a metal band heteroelectrode and employed it for the selective
      detection of catecholamines. We used an indium-tin oxide (ITO) film as the
      oxidation electrode of the IDAE because the ITO was able to suppress response
      currents from L-ascorbic acid (AA) and uric acid (UA), which are major
      electroactive interferents in biological fluids. However, the ITO film also
      suppresses the reduction of quinones including oxidized catecholamines. We
      developed a simple technique for fabricating our hetero IDAE, which also
      preserves the electrochemical properties of the ITO. When we compared hetero ITO
      gold, homo ITO-ITO, and carbon-carbon IDAEs, we found that the hetero IDAE
      provided both high sensitivity and selectivity for DA detection. We achieved high
      selectivities for DA against AA and UA. The ratios of the response currents of AA
      and UA to DA were calculated as 6 and 5%, respectively.

PMID- 16097765
TI  - Mapping of phosphorylation sites by a multi-protease approach with specific
      phosphopeptide enrichment and NanoLC-MS/MS analysis.
AB  - We have developed a multi-protease approach that allows sensitive and
      comprehensive mapping of protein phosphorylation sites. The combined application
      of the low-specificity proteases elastase, proteinase K, and thermolysin in
      addition to trypsin results in high sequence coverage, a prerequisite for
      comprehensive phosphorylation site mapping. Phosphopeptide enrichment is
      performed with the recently introduced phosphopeptide affinity material
      titansphere. We have optimized the selectivity of the phosphopeptide enrichment
      with titansphere, without compromising the high recovery rate of approximately
      90%. Phosphopeptide-enriched fractions are analyzed with a highly sensitive
      nanoLC-MS/MS system using a 25-microm-i.d. reversed-phase column, operated at a
      flow rate of 25 nL/min. The new approach was applied to the murine circadian
      protein period 2 (mPER2). A total of 21 phosphorylation sites of mPER2 have been
      detected by the multi-protease approach, whereas only 6 phosphorylation sites
      were identified using solely trypsin. Titansphere proved to be well suited for
      the enrichment of a large variety of phosphopeptides, including peptides carrying
      two, three, or four phosphorylated residues, as well as phosphopeptides
      containing more basic than acidic amino acids.

PMID- 16097766
TI  - Lithium isotope composition of basalt glass reference material.
AB  - We present data on the lithium isotope compositions of glass reference materials
      from the United States Geological Survey (USGS) and the National Institute of
      Standards and Technology (NIST) determined by multicollector inductively coupled
      plasma mass spectrometry (MC-ICPMS), thermal ionization mass spectrometry (TIMS),
      and secondary ionization mass spectrometry (SIMS). Our data on the USGS basaltic
      glass standards agree within 2 per thousand, independent of the sample matrix or
      Li concentration. For SIMS analysis, we propose use of the USGS glasses GSD-1G
      (delta(7)Li 31.14 +/- 0.8 per thousand, 2sigma) and BCR-2G (delta(7)Li 4.08 +/-
      1.0 per thousand, 2sigma) as suitable standards that cover a wide range of Li
      isotope compositions. Lithium isotope measurements on the silica-rich NIST 600
      glass series by MC-ICPMS and TIMS agree within 0.8 per thousand, but SIMS
      analyses show systematic isotopic differences. Our results suggest that SIMS Li
      isotope analyses have a significant matrix bias in high-silica materials. Our
      data are intended to serve as a reference for both microanalytical and bulk
      analytical techniques and to improve comparisons between Li isotope data produced
      by different methodologies.

PMID- 16097767
TI  - Immunomagnetic isolation of enterohemorrhagic Escherichia coli O157:H7 from
      ground beef and identification by matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry and database searches.
AB  - A rapid (25 min) and facile method was developed for the isolation and
      identification of the enterohemorrhagic Escherichia coli (serotype O157:H7) in
      ground beef. The isolation method employed microscopic magnetic beads coated with
      antibodies covalently bonded to the surface that were specific to antigens of
      serotype O157. This selective preconcentration step was necessary because direct
      matrix-assisted laser desorption/ionization (MALDI) MS analysis of bacteria was
      not amenable, serving to isolate the bacteria from meat components and other
      nontarget bacteria. The immunomagnetic separation increased the sensitivity of
      the method and permitted the detection of bacteria in meat. MALDI time-of-flight
      MS furnished bacterial mass spectra that were useful for organism identification.
      Molecular weight database searches using the Expert Protein Analysis System
      proved useful for confirmation of the organism's identity. Bacterial biomarkers
      from direct MALDI analysis of pure bacterial suspensions were consistently
      present in bacterial suspensions of buffer/tryptic soy broth (positive controls)
      and meat extract samples. The detection limits were 2 x 10(6) cells/mL for the
      experimental approach used herein. Cross-reactivity studies performed on three
      nontarget bacterial strains revealed that the immunomagnetic beads are specific
      only to E. coli strain serotype O157:H7, and there is no cross-reactivity with
      the other relatively innocuous strains studied.

PMID- 16097768
TI  - Fluorescein-labeled beta-lactamase mutant for high-throughput screening of
      bacterial beta-lactamases against beta-lactam antibiotics.
AB  - The increasing emergence of new bacterial beta-lactamases that can efficiently
      hydrolyze beta-lactam antibiotics to clinically inactive carboxylic acids has
      created an intractable problem in the treatment of bacterial infections, and it
      is highly desirable to develop a useful tool that can rapidly screen bacteria for
      beta-lactamases against a variety of antibiotic candidates in a high-throughput
      manner. This paper describes the use of a fluorescein-labeled beta-lactamase
      mutant (E166Cf) as a convenient fluorescent tool to screen beta-lactamases,
      including the Bacillus cereus beta-lactamase I (PenPC), B. cereus beta-lactamase
      II, Bacillus licheniformis PenP, Escherichia coli TEM-1, and Enterobacter cloacae
      P99 against various beta-lactam antibiotics (penicillin G, penicillin V,
      ampicillin, cefuroxime, cefoxitin, moxalactam, cephaloridine), using a 96-well
      microplate reader. The E166Cf mutant was constructed by replacing Glu166 on the
      flexible Omega-loop, which is close to the enzyme's active site, with a cysteine
      residue on a class A beta-lactamase (B. cereus PenPC) and subsequently labeling
      the mutant with thiol-reactive fluorescein-5-maleimide. Such modifications
      significantly impaired the hydrolytic activity of the E166Cf mutant compared to
      that of the wild-type enzyme. The fluorescence intensity of the E166Cf mutant
      increases in the presence of beta-lactam antibiotics. For antibiotics that are
      resistant to hydrolysis by the E166Cf mutant (cefuroxime, cefoxitin, moxalactam),
      the fluorescence signal slowly increases until it reaches a plateau. For
      antibiotics that can be slowly hydrolyzed by the E166Cf mutant (penicillin G,
      penicillin V, ampicillin), the fluorescence signal rapidly increases to the
      plateau and then declines after a prolonged incubation. The E166Cf mutant retains
      its characteristic pattern of fluorescence signals in the presence of both
      bacterial beta-lactamases and beta-lactamase-resistant antibiotics. In contrast,
      in the presence of both bacterial beta-lactamases and beta-lactamase-sensitive
      antibiotics, the fluorescence signals of the E166Cf mutant were decreased. The
      fluorescence signals from the E166Cf mutant allow an unambiguous differentiation
      of beta-lactamase-resistant antibiotics from beta-lactamase-sensitive ones in the
      screening of bacterial beta-lactamases against a panel of antibiotic candidates.
      This simple method may provide an alternative tool in choosing potent beta-lactam
      antibiotics for treatment of bacterial infections.

PMID- 16097769
TI  - Atmospheric pressure photoionization for enhanced compatibility in on-line
      micellar electrokinetic chromatography-mass spectrometry.
AB  - Atmospheric pressure photoionization (APPI) is presented as a novel means for the
      combination of micellar electrokinetic chromatography (MEKC) and mass
      spectrometry (MS). The on-line coupling is achieved using an adapted sheath flow
      interface installed on an orthogonal APPI source. Acetone or toluene is added as
      dopant to the sheath liquid to enhance analyte photoionization. It is
      demonstrated that with APPI signal suppression and interferences by the
      surfactant sodium dodecyl sulfate (SDS) and nonvolatile buffers can be
      circumvented. This implies that MEKC conditions can be selected independently
      from MS detection. Moreover, it is shown that both polar and apolar compounds can
      be photoionized, thereby also facilitating the analysis of compounds that are not
      amenable to electrospray ionization. Consequently, the MEKC-APPI-MS system can
      provide effective separation and detection of compounds of diverse character in
      one run using background electrolytes containing up to 50 mM SDS. Concentration
      limits of detection derived from extracted-ion traces (full scan mode) of test
      compounds were approximately 1 microg/mL, and the detection sensitivity remained
      unaffected during 1 day of continuous use. Overall, the system features are very
      favorable for applications such as drug impurity profiling as is illustrated by
      the analysis of mebeverine and related compounds (both charged and neutral) at
      the 0.25% (w/w) level.

PMID- 16097770
TI  - Direct competitive enzyme-linked immunosorbent assay for the determination of the
      highly polar short-chain sulfophenyl carboxylates.
AB  - A direct enzyme-linked immunosorbent assay for the detection of the short-chain
      sulfophenylcarboxylic acids (SPCs), the main metabolites of the linear
      alkylbenzenesulfonates, is reported. Six SPCs (2C3, 2C4, 3C4, 2C5, 3C5, 3C6),
      differing in the length of the alkyl chain (between C3 and C6) and in the
      position of the phenylsulfonic group versus the carboxylic group, have been
      synthesized. Antibodies have been raised against a mixture of the corresponding
      horseshoe crab hemocyanin conjugates prepared by coupling the carboxylic acid to
      the lysine amino acid residues. The immunoassay As115/3C4-HRP achieves an IC50
      value of 23 nM (6.67 microg L(-1)) and a detection limit of 0.85 nM (0.24 microg
      L(-1)), using as standard analyte an equimolar mixture of the six SPCs. The
      immunoassay has found to work better in media with low or moderate ionic strength
      (4-30 mS cm(-1)). The decrease in the detectability produced by the potential
      formation of SPC salts with divalent cations such as Ca2+ can be prevented by
      lowering the pH of the assay medium below the pKa value of the SPC carboxylic
      group and using a buffer chelating with properties such as citrate buffer. The
      assay can be considered specific for short-chain SPCs since congeners with longer
      alkyl chains and other pollutants containing sulfonic groups in their structure
      do not interfere significantly in the assay. Preliminary experiments addressed to
      evaluate the potential application of this assay to environmental water samples
      demonstrate the usefulness of the assay.

PMID- 16097771
TI  - Cell sorting by one gravity SPLITT fractionation.
AB  - The need for innovative separative techniques suitable for the fractionation of
      biomaterials prompted this investigation into the performance of the
      gravitational split-flow thin channel (G-SPLITT) system as a cell sorter. The
      rigorous mathematical description of the separation mechanism allows achievement
      of fast separation of several million myeloma cells from healthy splenocytes
      using flow conditions calculated from theory. Separation in G-SPLITT is based on
      differences in sedimentation rate. For accurate prediction of the optimal working
      conditions, this parameter was directly measured by cell tracking velocimetry
      rather than relying on a measure of diameter (by Multisizer) and an assumed
      density for each cell population. We also discuss the influence of different flow
      conditions on the effectiveness of separation.

PMID- 16097772
TI  - Chiral melamine derivatives: design, synthesis, and application to mass
      spectrometry-based chiral analysis.
AB  - A novel class of chiral melamine derivatives has been designed and synthesized.
      The ability of these compounds to perform chiral recognition toward 19 natural
      chiral alpha-amino acids has been investigated by electrospray ionization tandem
      mass spectrometry for the first time. The enantioselectivities of these new
      chiral selectors are encouraging. To elucidate some mechanism and regularity in
      the chiral recognition process using chiral melamine derivatives as chiral
      selectors, the effect of different noncovalent interactions caused by various
      chiral or achiral moieties in melamine derivatives on the chiral recognition in
      the gas phase has been studied at the same time. The result shows that
      electrostatic, hydrogen bond, pi-pi stacking, and steric interaction between
      selector and analyte play important roles in the association and enantioselective
      recognition of amino acids with the chiral melamine derivatives as chiral
      selectors. Enantiodiscrimination for analytes with different structures and
      properties could be improved by modifying substituents in melamine derivatives on
      purpose.

PMID- 16097773
TI  - Compound screening for the presence of the primary N-oxide functionality via ion
      molecule reactions in a mass spectrometer.
AB  - A mass spectrometry method is presented for the identification of compounds that
      contain the primary N-oxide functional group. This method utilizes a gas-phase
      ion-molecule reaction with dimethyl disulfide that rapidly and selectively
      derivatizes the protonated primary N-oxide functional group in a mass
      spectrometer to yield an ionic reaction product (with 31 Da higher mass than that
      of the protonated molecule) that is diagnostic for the presence of a primary N
      oxide functionality. A variety of protonated analytes containing different
      functional groups were tested in Fourier transform ion-cyclotron resonance and
      triple quadrupole mass spectrometers to probe the selectivity of the reaction.
      Only molecules containing the protonated primary N-oxide functional group yielded
      the diagnostic reaction product; all other protonated molecules gave protonated
      dimethyl disulfide or no reaction products. The feasibility of this method for
      compound screening was tested by examining six analytes with the same molecular
      formula but different atom connectivity. The one analyte that contained the
      primary N-oxide functional group was readily differentiated from the other
      analytes.

PMID- 16097774
TI  - Determination of (111) ordered domains on platinum electrodes by irreversible
      adsorption of bismuth.
AB  - Irreversible adsorbed bismuth can be used to determine the fraction of (111)
      domains on a given platinum sample. On Pt(111) electrodes, the surface redox
      process of adsorbed bismuth takes place at 0.63 V in a well-defined peak. The
      behavior of this redox process on the Pt(111) vicinal surfaces indicates that the
      bismuth atoms involved in the redox process are only those deposited on the (111)
      terrace sites and that the charge under the peak at 0.63 V is directly
      proportional to the number of sites on (111) ordered domains (terraces). The good
      linear relationship obtained between the charge for the bismuth redox process and
      the number of (111) terrace sites on the vicinal surfaces allows construction of
      a calibration curve. This calibration curve has been used to directly estimate
      the amount of (111) ordered domain terrace sites on polycrystalline platinum
      samples with different surface ordered domains. The results agree with what we
      would expect from our knowledge of these surfaces.

PMID- 16097776
TI  - Chemical suppression of contaminant metal ions using a metastable state in
      precolumn derivatizing HPLC: an ultratrace fluorometric detection of Al(III).
AB  - The contamination of metal ions from reagents used frequently restricts the
      practical detection limit of the metal ion, which itself is a source of
      contamination. We have found a novel solution to this problem, a chemical
      suppressing method of contaminant metal ions on a reversed-phase HPLC for Al3+
      with a detection limit of 7.6 x 10(-11) mol dm(-3) (2.1 ng dm(-3)) by only adding
      a certain agent into all stock solutions without any preconcentration or
      purification steps. This technique decreases the concentration of the contaminant
      Al3+ originating from the reagents by more than 1 order of magnitude using
      selective derivatization of sample Al3+ ions to a powerful fluorescent complex at
      a metastable state in the precolumn chelation processes. Meanwhile, the
      contaminant Al3+ remains as a nonfluorescent complex with a blocking reagent in
      order to suppress the contamination. This selective derivatization is achieved by
      the accumulation of several complexation processes based on the difference of
      formation, dissociation, and ligand-exchange kinetics and the thermodynamics
      between the derivatizing reagent, the 4',5'-geometorical isomer of calcein, and
      the blocking reagent, o,o'-dihydroxyazobenzene. This simple and smart HPLC system
      was validated through recovery tests of environmental and biological samples.

PMID- 16097775
TI  - Toward a global analysis of the human pituitary proteome by multiple gel-based
      technology.
AB  - We describe a comprehensive method for the analysis of complex proteomes,
      multiple gel-based technology (MGT), which combines in-gel IEF-LC-MS/MS and SDS
      PAGE-LC-MS/MS strategies. MGT was applied to the analysis of the proteome of
      human pituitary tissue. A total of 1449 proteins were uniquely identified. To our
      knowledge, this is the most comprehensive proteomic analysis of human pituitary
      tissue to date. Categorization of the identified proteins revealed that MGT
      provides an excellent and largely unbiased access to proteins with diverse
      characteristics, including low-abundance proteins, membrane proteins, and
      proteins with extremes in pI and MW.

PMID- 16097777
TI  - Electrochemistry and electrogenerated chemiluminescence with a single faradaic
      electrode.
AB  - We describe an electrochemical cell containing a single faradic electrode (a Pt
      ultramicroelectrode) and a blocked (polarized) electrode (Si with an insulating
      SiO2 film) that served as a capacitive counter electrode. When a bias was applied
      between the two electrodes, a current was observed from a faradic process at Pt
      and a capacitive current at the blocking electrode. A steady charging current was
      obtained when the solution was moved along the insulator to continuously contact
      fresh surface (emersing a layer of charged ions and electronic countercharge into
      the gas phase). Electrogenerated chemiluminescence was clearly observed from a
      system containing Ru(bpy)(3)2+ in this kind of cell under pulsed excitiation,
      demonstrating that faradaic reactions can be carried out in an electrochemical
      cell without generation of any products at a counter electrode. The use of such a
      system for coulometric addition of desired species in nanosystems and in
      synthesis is suggested.

PMID- 16097778
TI  - Removal of an iron matrix with polyoxyethylene-type surfactant-coated amberlite
      XAD-4 for the determination of trace impurities in high-purity iron.
AB  - Admicellar sorbents for the removal of an iron matrix were prepared for the
      determination of trace impurities in high-purity iron. A 1.0-g amount of
      Amberlite XAD-4 (macroreticular styrene-divinylbenzene copolymer) was coated with
      0.14-1.3 mmol of polyoxyethylene-type surfactants, including polyoxyethylene-4
      tert-octylphenoxy ethers (Triton X series) and polyoxyethylene-4-isononylphenoxy
      ethers (PONPEs). The surfactant-coated XAD-4 was packed into a polypropylene
      column (7 mm i.d. x 50 mm high). A 5.0-cm(3) volume of sample solution was passed
      through the column at a flow rate of 0.5 cm(3) min(-1). Milligram amounts of
      iron(III) were effectively sorbed on the column from 8 mol dm(-3) hydrochloric
      acid solutions. Among the surfactants tested, polyoxyethylene(20)-4
      isononylphenoxy ether (PONPE-20) showed the best performance: the iron leaked
      from the PONPE-20 column was 4 microg when 25 mg of iron(III) was introduced onto
      the column. Trace elements, such as Ti(IV), Cr(III), Mn(II), Co(II), Ni(II),
      Cu(II), Zn(II), Ag(I), Cd(II), Pb(II), and Bi(III), were not retained on the
      column and thus quantitatively recovered in the column effluent. The effective
      separation of trace elements from an iron matrix allowed their accurate
      determinations by inductively coupled plasma-mass spectrometry or graphite
      furnace atomic absorption spectrometry. The detection limits (3sigma blank) were
      in the nanogram per gram range. The proposed method was successfully applied to
      the determination of trace impurities in high-purity iron samples.

PMID- 16097779
TI  - Microcolumn separation of amine metabolites in the fruit fly.
AB  - Electrophoretic resolution of 14 biogenic amines and metabolites with similar
      mobilities is addressed by employing micellar electrokinetic capillary
      chromatography coupled to amperometric electrochemical detection. The present
      study describes the optimization of separation conditions to achieve resolution
      of analytes of biological significance within 20 min in a single separation. They
      include dopamine, epinephrine, norepinephrine, octopamine (OA), L-3, 4
      dihydroxyphenylalanine, tyramine (TA), and serotonin as well as metabolites 5
      hydroxyindolacetic acid, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 3
      methoxytyramine in addition to N-acetylated metabolites including N
      acetyldopamine, N-acetyloctopamine (naOA), and N-acetylserotonin. The optimized
      conditions used result in excellent reproducibility and predictable peak
      shifting, thus enabling identification of several metabolites along with their
      biogenic amine precursors in biological samples, specifically from the fruit fly
      Drosophila melanogaster. The separation method is sensitive, selective, and
      quantitative as demonstrated by its capacity to detect changes in TA, OA, and
      naOA present in the head homogenates of the Canton-S and mutant inactive(1)
      Drosophila lines. Quantitative analysis of metabolites in conjunction with their
      biogenic amine precursors in a single separation offers tremendous potential to
      understand the physiological processes and underlying mechanisms mediated by
      various biogenic amines in Drosophila and other animals.

PMID- 16097780
TI  - Poly(dimethylsiloxane)-based microchip for two-dimensional solid-phase extraction
      capillary electrophoresis with an integrated electrospray emitter tip.
AB  - A microchip in poly(dimethylsiloxane) (PDMS) for in-line solid-phase extraction
      capillary electrophoresis-electrospray ionization-time-of-flight mass
      spectrometry (SPE-CE-ESI-TOF-MS) has been developed and evaluated. The chip was
      fabricated in a novel one-step procedure where mixed PDMS was cast over steel
      wires in a mold. The removed wires defined 50-microm cylindrical channels. Fused
      silica capillaries were inserted into the structure in a tight fit connection.
      The inner walls of the inserted fused-silica capillaries and the PDMS microchip
      channels were modified with a positively charged polymer, PolyE-323. The chip was
      fabricated in a two-level cross design. The channel at the lower level was packed
      with 5-microm hyper-cross-linked polystyrene beads acting as a SPE medium used
      for desalting. The upper level channel acted as a CE channel and ended in an
      integrated emitter tip coated with conducting graphite powder to facilitate the
      electrical contact for sheathless ESI. An overpressure continuously provided
      fresh CE electrolyte independently of the flows in the different levels. Further
      studies were carried out in order to investigate the electrophoretic and flow
      rate properties of the chip. Finally, six-peptide mixtures, in different
      concentrations, dissolved in physiological salt solution was injected, desalted,
      separated, and sprayed into the mass spectrometer for analysis with a limit of
      detection in femtomole levels.

PMID- 16097781
TI  - Requirements for laser-induced desorption/ionization on submicrometer structures.
AB  - Laser-induced and matrix-free desorption/ionization on various submicrometer
      structures was investigated. First, to examine the effect of surface roughness on
      ionization, a silicon wafer or stainless steel was scratched with sandpaper. The
      fluences of a 337-nm nitrogen laser, required for ionization of synthetic
      polymers and reserpine, were markedly reduced on the scratched stainless steel or
      silicon as compared to the corresponding untreated surface. Next, arrays of
      submicrometer grooves, which had been lithographically fabricated on a silicon
      wafer, yielded protonated angiotensin, and the morphologic orientation
      demonstrated the positive relation between the laser and groove directions for
      promoting ionization. The fabricated structure also suggested the submicrometer,
      but not smaller, or nanometer, structures to be a key factor in direct
      desorption/ionization on rough surfaces. Finally, submicrometer porous structures
      of alumina or polyethylene yielded intense molecular ion signals of angiotensin
      and insulin, in response to direct UV irradiation, when the surface was coated
      with Au or Pt. The coating provided the additional advantage of prolonged
      activity for a porous alumina chip, exceeding a month even when the chip was left
      in the open air. These results indicate that laser-induced desorption/ionization
      of organic compounds can be implemented on submicrometer structures with an Au-
      or Pt-coated surface irrespective of the basal materials.

PMID- 16097782
TI  - Estimates of protein surface areas in solution by electrospray ionization mass
      spectrometry.
AB  - The extent of multiple charging of protein ions in electrospray ionization (ESI)
      mass spectra depends on the solvent-exposed surface area, but it may also be
      influenced by a variety of other extrinsic and intrinsic factors. Gas-phase ion
      chemistry (charge-transfer and charge-partitioning reactions) appears to be the
      major extrinsic factor influencing the extent of protonation as detected by ESI
      MS. In this work, we demonstrate that under carefully controlled conditions,
      which limit the occurrence of the charge-transfer reactions in the gas phase,
      charge-state distributions of protein ions can be used to assess the solvent
      exposed surface area in solution. A set of proteins ranging from 5-kDa insulin to
      500-kDa ferritin shows a clear correlation between the average charge in ESI mass
      spectra acquired under native conditions and their surface areas calculated based
      on the available crystal structures. An increase of the extent of charge-transfer
      reactions in the ESI interface results in a noticeable decrease of the average
      charge of protein ions across the entire range of tested proteins, while the
      charge-surface correlation is maintained. On the other hand, the intrinsic
      factors (e.g., a limited number of basic residues) do not appear to play a
      significant role in determining the protein ion charge. Based on these results,
      it is now possible to obtain estimates of the surface areas of proteins and
      protein complexes, for which crystal structures are not available. We also
      demonstrate how the ESI MS measurements can be used to characterize protein
      protein interaction in solution by providing quantitative information on the
      subunit interfaces formed in protein associations.

PMID- 16097783
TI  - Mathematical model describing gradient focusing methods for trace analytes.
AB  - The problem of gradient focusing for concentrating trace analytes is considered.
      Variation of buffer viscosity, conductivity, and possibly also the zeta-potential
      results in a focusing point where the electrophoretic velocity is balanced by the
      electroosmotic flow (EOF) and where the sample concentrates. The axial
      inhomogeneity also results in an induced pressure gradient that alters the EOF
      profile and therefore causes Taylor dispersion. The coupled hydrodynamics and
      transport problem leading to the achievement of a steady state is studied in the
      context of the lubrication approximation: all variations in the axial direction
      take place over a length scale very much larger than the characteristic channel
      width. A single length scale sigma(m) and a single time scale tau is found to
      completely determine the dynamics of the evolution close to the focusing point.
      Using appropriate scaled variables, the time evolution of the concentration
      profile near equilibrium can be described by an inhomogeneous advection diffusion
      equation that is free of all parameters. Explicit formulas are deduced for the
      location of the peak centroid and its width as a function of time. A simple
      graphical method is proposed for optimizing the performance of the system when
      some tunable external parameters are available.

PMID- 16097784
TI  - Fabrication of a poly(dimethylsiloxane)-based electrochemiluminescence detection
      cell for capillary electrophoresis.
AB  - An easy but effective technique is described here for quick fabrication of low
      cost electrochemiluminescence detection cells for capillary electrophoresis. The
      technique is based on molding of poly(dimethylsiloxane) (PDMS) with a capillary
      column inserted into a pipet tip. Two access holes are left in the PDMS slab;
      they provide neat accommodations for the separation capillary and the working
      electrode made with the same type of tip. Since the access holes are well
      aligned, the electrode and the capillary are automatically aligned; thus, end
      column detection is easily obtained. Fabrication of the detection cell is
      straightforward; no micromechanical operation is included. Also the principle for
      the procedure makes it possible to efficiently batch production detection cells
      with good reproducibility. Because of the end-column scheme, the cell can be
      adopted for electrophoresis with electrochemical detection as well.

PMID- 16097785
TI  - Speciation of organometallic compounds in environmental samples by gas
      chromatography after flow preconcentration on fullerenes and nanotubes.
AB  - The development of a simple speciation method for the determination of lead
      (trimethyllead(I), dimethyllead(II), triethyllead(I), and diethyllead(II)),
      mercury (methylmercury(I), ethylmercury(I), mercury(II)), and tin (n
      butyltin(III), di-n-butyltin(II), tri-n-butyltin(I), tin(IV)) compounds in
      environmental samples was described. The potential of C70 fullerenes and
      multiwalled carbon nanotubes (MWNTs) as sorbents was investigated for the first
      time; this study revealed that there are no significant differences between them
      in terms of sensitivity, selectivity, precision, and reusability. Comparative
      studies showed that MWNTs and C60 and C70 fullerenes were superior to graphitized
      carbon black and RP-C18 for the extraction of the 11 compounds studied. The
      accuracy of the MWNT method was evaluated from recovery values with two standard
      reference coastal sediments, and good concordance in the results were obtained.
      Detection limits of 0.5-2 pg/mL were obtained when using a sorbent column
      containing 160 mg of MWNTs (sample breakthrough, 50 mL of water). The method was
      successfully applied to the determination of lead, mercury, and tin compounds in
      water and coastal sediment samples with satisfactory results.

PMID- 16097786
TI  - Octadecyl immobilized surface for precipitate collection with a renewable
      microcolumn in a lab-on-valve coupled to an electrothermal atomic absorption
      spectrometer for ultratrace cadmium determination.
AB  - Octadecyl immobilized surface was, for the first time, proved to be a superb
      precipitate-collecting medium. Surface charge effect was assumed to dominate the
      adsorption of cadmium hydroxide precipitate, facilitated by electrostatic
      interaction between the negatively charged C18 bead surface and positively
      charged cadmium hydroxide clusters. Residual silanol groups on the C18
      immobilized silica surface did not contribute to precipitate adsorption. A novel
      procedure for ultratrace cadmium preconcentration was proposed by incorporating a
      renewable microcolumn in a lab-on-valve system. Cd(OH)(2) precipitate was
      adsorbed onto the C18 surface, which was afterward eluted with 20 microL of
      nitric acid (1%) and quantified with detection by electrothermal atomic
      absorption spectrometry. An enrichment factor of 28 and a limit of detection of
      1.7 ng L(-1), along with a sampling frequency of 13 h(-1) were obtained with a
      sample consumption of 600 microL within the concentration range of 0.01-0.2
      microg L(-1), achieving a precision of 2.1% RSD at the 0.05 microg L(-1) level.
      The enrichment factor was further enhanced to 44 by increasing the sample volume
      to 1200 microL. The procedure was validated by analyzing cadmium in three
      certified reference materials, that is, river sediment (CRM 320), sea lettuce
      (CRM 279), and frozen cattle blood (GBW 09140). Good agreement between the
      obtained results and the certified values was achieved.

PMID- 16097787
TI  - Chemical reaction interface mass spectrometry with high efficiency nebulization.
AB  - A high efficiency nebulizer (HEN) coupled to a heated spray chamber and a
      membrane desolvator is used for liquid sample introduction in chemical reaction
      interface mass spectrometry (CRIMS). Compared to the conventional thermospray
      nebulizer operated at solvent flow rate of 1 mL/min, the HEN provides small
      droplets at lower flow rates (10-100 microL/min), improving the desolvation and
      analyte transport efficiency. As a result, the sensitivity for carbon detection
      by CRIMS is improved by a factor of 4. The new arrangement offers an easy-to-use
      and robust interface, facilitating the availability of a variety of liquid
      chromatographic techniques to the CRIMS. Separation and detection of labeled
      peptides in a mixture of unlabeled biopolymers is illustrated at a solvent flow
      rate of 45 microL/min as an example of new possibilities offered by the improved
      liquid introduction interface.

PMID- 16097788
TI  - Automated on-line column-switching HPLC-MS/MS method with peak focusing for the
      determination of nine environmental phenols in urine.
AB  - We developed a method using isotope dilution on-line solid-phase extraction (SPE)
      coupled to high-performance liquid chromatography-tandem mass spectrometry (HPLC
      MS/MS) for the determination in urine of nine environmental phenolic compounds:
      Bisphenol A; 4-tert-octylphenol; o-phenylphenol; 2,4-dichlorophenol; 2,5
      dichlorophenol; 2,4,5-trichlorophenol; 2,4,6-trichlorophenol; benzophenone-3 (2
      hydroxy-4-metoxybenzophenone); and triclosan (2,4,4'-trichloro-2'-hydroxyphenyl
      ether). A unique fully automated column-switching system, constructed using 1
      autosampler, 2 HPLC pumps, and a 10-port switching valve, was designed to allow
      for concurrent SPE-HPLC operation with peak focusing. The phenols present in 100
      microL of urine were retained and concentrated on a C18 reversed-phase size
      exclusion SPE column. Then, the phenols were "back-eluted" from the SPE column
      and diluted through a mixing Tee before being separated from other urine matrix
      components using a pair of monolithic HPLC columns. The phenols were detected by
      negative ion-atmospheric pressure chemical ionization-MS/MS. The efficient
      preconcentration of the phenols by the SPE column, analyte peak focusing by the
      dilution, and minimal ion suppression in the LC/MS interface by the buffer-free
      mobile phases resulted in limits of detection as low as 0.1-0.4 ng/mL for most
      analytes. The method was validated on spiked pooled urine samples and on urine
      samples from 30 adults with no known occupational exposure to environmental
      phenols. The method can be used for quick and accurate analysis of large numbers
      of samples in epidemiologic studies for assessing the prevalence of human
      exposure to environmental phenols.

PMID- 16097789
TI  - Wafer-scale fabrication of polymer-based microdevices via injection molding and
      photolithographic micropatterning protocols.
AB  - Because of their broad applications in biomedical analysis, integrated, polymer
      based microdevices incorporating micropatterned metallic and insulating layers
      are significant in contemporary research. In this study, micropatterns for
      temperature sensing and microelectrode sets for electroanalysis have been
      implemented on an injection-molded thin polymer membrane by employing
      conventional semiconductor processing techniques (i.e., standard
      photolithographic methods). Cyclic olefin copolymer (COC) is chosen as the
      polymer substrate because of its high chemical and thermal stability. A COC 5-in.
      wafer (1-mm thickness) is manufactured using an injection molding method, in
      which polymer membranes (approximately 130 microm thick and 3 mm x 6 mm in area)
      are implemented simultaneously in order to reduce local thermal mass around
      micropatterned heaters and temperature sensors. The highly polished surface
      (approximately 4 nm within 40 microm x 40 microm area) of the fabricated COC
      wafer as well as its good resistance to typical process chemicals makes it
      possible to use the standard photolithographic and etching protocols on the COC
      wafer. Gold micropatterns with a minimum 5-microm line width are fabricated for
      making microheaters, temperature sensors, and microelectrodes. An insulating
      layer of aluminum oxide (Al2O3) is prepared at a COC-endurable low temperature
      (approximately 120 degrees C) by using atomic layer deposition and
      micropatterning for the electrode contacts. The fabricated microdevice for
      heating and temperature sensing shows improved performance of thermal isolation,
      and microelectrodes display good electrochemical performances for electrochemical
      sensors. Thus, this novel 5-in. wafer-level microfabrication method is a simple
      and cost-effective protocol to prepare polymer substrate and demonstrates good
      potential for application to highly integrated and miniaturized biomedical
      devices.

PMID- 16097790
TI  - Direct chromatographic determination of dissociation rate constants of ligand
      receptor complexes: assessment of the interaction of noncompetitive inhibitors
      with an immobilized nicotinic acetylcholine receptor-based liquid chromatography
      stationary phase.
AB  - A liquid chromatographic stationary phase containing immobilized membranes from a
      cell line expressing the alpha3beta4 subtype of the neuronal nicotinic
      acetylcholine receptor (nAChR) has been used to assess dissociation rate
      constants (kd) of 12 noncompetitive inhibitor-nAChR complexes. The
      pharmacological effects of the noncompetitive inhibitors, expressed as percent
      recovery of activity at 7 min and 4 h postexposure to the inhibitor, were also
      determined. The results demonstrate that the kd values correlated with the
      pharmacological effect and that this approach can be used to identify molecular
      structures associated with differences in kd values. The method can be adapted
      for use with membrane-bound receptors, ion channels, and transporters and
      represents a direct and facile technique for the assessment of dissociation rate
      constants (kd) of ligand-receptor complexes.

PMID- 16097791
TI  - Mutagenesis of 8-oxoguanine adjacent to an abasic site in simian kidney cells:
      tandem mutations and enhancement of G-->T transversions.
AB  - Clustered DNA damages are well-established characteristics of ionizing radiation.
      As a model clustered lesion in the same strand of DNA, we have evaluated the
      mutagenic potential of 8-oxoguanine (8-oxoG) adjacent to a uracil in simian
      kidney cells using a phagemid vector. The uracil residue would be excised by the
      enzyme uracil DNA glycosylase in vivo generating an abasic site (AP site). A
      solitary uracil in either GUGTC or GTGUC sequence context provided >60% progeny
      containing GTGTC indicating that dAMP incorporation opposite the AP site or
      uracil occurred, but a >30% population showed replacement of U by A, C, or G,
      which suggests that dTMP, dGMP, or dCMP incorporation also occurred,
      respectively, opposite the AP site. While the preference for targeted base
      substitutions at the GUG site was T >> C > A > G, the same at the GUC site was T
      >> A > C > G. We conclude that base incorporation opposite an AP site is sequence
      dependent. For 8-oxoG, as compared to 23-24% G-->T mutants from a single 8-oxoG
      in a TG(8-oxo)T sequence context, the tandem lesions UG(8-oxo)T and TG(8-oxo)U
      generated approximately 60 and >85% progeny, respectively, that did not contain
      the TGT sequence. A significant fraction of tandem mutations were detected when
      uracil was adjacent to 8-oxoG. What we found most interesting is that the total
      targeted G(8-oxo)-->T transversions that included both single and tandem
      mutations at the TG(8-oxo)U site was nearly 60% relative to about 30% at the UG(8
      oxo)T site. A higher mutational frequency at the TG(8-oxo)U sequence may arise
      from a change in DNA polymerase that is more error prone. Thermal melting
      experiments showed that the Tm for the 8-oxoG:C pair in the TG(8-oxo)(AP*)
      sequence in a 12-mer was lower than the same in a (AP*)G(8-oxo)T 12-mer with
      deltadeltaG 0.8 kcal/mol (where AP* represents tetrahydrofuran, the model abasic
      site). When the 8-oxoG:C pair in each sequence was compared with a 8-oxoG:A pair,
      the former was found to be more stable than the latter. The preference for C over
      A opposite 8-oxoG for the (AP*)G(8-oxo)T 12-mer duplex with a deltadeltaG of 1.6
      kcal/mol dropped to 0.4 kcal/mol in the TG(8-oxo)(AP*) 12-mer duplex. This
      suggests that the polymerase discrimination to incorporate dCMP over dAMP would
      be less efficient in the TG(8-oxo)(AP*) sequence relative to (AP*)G(8-oxo)T.
      Additionally, the efficiency of recognition and excision of A opposite 8-oxoG by
      a mismatch repair protein may be impaired in the TG(8-oxo)(AP*) sequence context.

PMID- 16097792
TI  - Gene expression profiling in a model of D-penicillamine-induced autoimmunity in
      the Brown Norway rat: predictive value of early signs of danger.
AB  - Idiosyncratic drug reactions (IDRs) cause significant morbidity and mortality. In
      an animal model of IDRs, 50-80% of Brown Norway rats exposed to D-penicillamine
      develop an autoimmune syndrome after several weeks of treatment. The symptoms of
      the IDR are similar to that observed in humans who take D-penicillamine. The
      mechanism of this reaction is unknown, and no effective biomarkers have been
      identified to predict susceptibility. We postulate that cell stress caused by
      drugs is required to initiate the response. We used a high-throughput approach to
      identify factors that might represent danger signals by profiling hepatic gene
      expression 6 h after dosing with D-penicillamine (150 mg/kg). Our results show
      that the drug-treated animals cluster into two distinct groups. One group
      exhibits substantial expression changes relative to control animals. The most
      significantly altered transcripts have a role in stress, energy metabolism, acute
      phase response, and inflammation. We used quantitative reverse transcriptase
      polymerase chain reaction to measure transcript levels in liver biopsies of 33
      rats and found that resistant animals cluster together. This "resistant" cluster
      of animals contains 87.5% (7/8) resistant animals but only 48% (12/25)
      "sensitive" animals. This separation is statistically significant at the p = 0.01
      level.

PMID- 16097793
TI  - The highly conserved Glu149 and Tyr190 residues contribute to peroxynitrite
      mediated nitrotyrosine formation and the catalytic activity of cytochrome P450
      2B1.
AB  - Tyr190 in cytochrome P450 2B1 has previously been shown to be a prime target for
      nitration by peroxynitrite (PN) resulting in nitrotyrosine formation and the
      inactivation of this enzyme. Modeling studies have suggested that Tyr190 may play
      a structural role in maintaining the integrity of the protein for maximal
      activity through hydrogen bonding with Glu149. To elucidate the roles of Tyr190
      and Glu149 hydrogen-bonding in maintaining the catalytically competent structure
      of P450 2B1, we have mutated Tyr190 to Phe or Ala and Glu149 to Gln or Ala to
      characterize the catalytic activities and the structural stabilities of mutated
      proteins. The results demonstrate that (a) the catalytic activities of all four
      mutants were decreased significantly compared to wild-type (WT); (b) nitration of
      Tyr190 by PN or mutation of Tyr190 to Phe did not alter the Km of the reductase
      for P450; (c) PN decreases the catalytic activity of the heat-treated Y190A,
      E149Q, and E149A mutants to a much greater extent than the WT and Y190F; and (d)
      after exposure of the P450s to PN, the extent of nitrotyrosine formation and the
      inactivation of the catalytic activity of the E149Q and E149A mutants were
      markedly decreased when compared to WT. These findings suggest that (1) the
      hydrogen bond between Tyr190 and Glu149 stabilizes the protein for maximal
      activity; (2) the benzyl ring and hydroxyl groups of Tyr190 stabilize the protein
      structure when P450 is exposed to the temperatures higher than 45 degrees C; and
      (3) Glu149 may be critical in directing the site of nitration by PN. Since Glu149
      and Tyr190 are both highly conserved in the P450 2 family, they may play an
      important role in the tertiary structure and functional properties of these
      P450s.

PMID- 16097794
TI  - Nitrosative cytosine deamination. An exploration of the chemistry emanating from
      deamination with pyrimidine ring-opening.
AB  - A discussion of nitrosative deamination of cytosine 1 is presented that argues
      for the formation of 6 by diazotization of 1 to cytosinediazonium ion 2 and its
      electrostatic complex 3, dediazoniation to 4 <--> 5, and amide-bond cleavage to
      6. The reaction channels available to 6 include hydrolytic deglycation to 3
      isocyanatoacrylonitrile 7, water addition to carbamic acid 9 with the possibility
      for re-closure to uracil 13, water addition to carbamic acid 9, and
      decarboxylation to 3-aminoacrylonitrile 10. With a view to the instability of the
      carbamic acid 9, the carbamate models ethyl (Z)-2-cyanovinylcarbamate 14 and (Z)
      2-cyano-1-tert-butylvinylcarbamate 20 were studied. Acid-catalyzed hydrolysis of
      14 leads to 2-amino-carbonylphenylcarbamate 15, and its cyclization yields the
      benzo-fused uracil quinazoline-2,4-dione 16. In contrast to the aromatic system
      14, acid-catalyzed cyclization cannot compete with oligomerization in the case of
      20, and 5-tert-butyluracil 22 is accessible only with base-catalysis. It is shown
      that 23, the parent of 10, also easily polymerizes. The experimental results
      provide a rationale as to why 9, 10, and 12 would have escaped detection in in
      vitro studies: they would have oligomerized. In contrast to the in vitro
      experiments, the oligomerizations of 9, 10, or 12 clearly are not relevant in
      vivo because of low monomer concentrations. With the exclusion of recyclization
      and of oligomerization in vivo, attention thus needs to focus on (Z)-3
      aminoacrylonitrile 10 as the most likely deamination product of cytosine aside
      from uracil.

PMID- 16097795
TI  - 4-Oxo-2-nonenal is both more neurotoxic and more protein reactive than 4-hydroxy
      2-nonenal.
AB  - Electrophilic aldehydes, generated from oxidation of polyunsaturated fatty acyl
      chains under conditions of oxidative stress, bind to proteins and polynucleotides
      and can lead to cell death. 4-Hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE)
      have been shown here to be toxic to human neuroblastoma cells in culture at low
      micromolar concentrations. ONE is 4-5 times more neurotoxic at concentrations
      near the threshold of lethality. The reactions of these two aldehydes with two
      model proteins, ribonuclease A and beta-lactoglobulin, and their Lys epsilon
      dimethylamino derivatives, have been followed spectrophotometrically. On the
      basis of t(1/2) measurements for the disappearance of the alpha,beta-unsaturated
      chromophore, ONE is 6-31 times more reactive with these proteins. The fastest
      reaction of ONE with proteins involves Schiff base formation at Lys epsilon-amino
      groups, whereas Schiff base formation is not spectroscopically apparent for HNE.
      Detailed kinetic studies of the initial reactions of HNE and ONE have been
      carried out with amino acids and amino acid surrogates. Whereas the reactions
      with imidazole and thiol nucleophiles involve straightforward Michael adduct
      formation, kinetics analyses reveal the reversibility of both the HNE Michael
      adduction of amines and the ONE Schiff base adduction of amines. Although ONE is
      more reactive than HNE toward conjugate addition of imidazole and thiol
      nucleophiles, it is less reactive than HNE toward Lys/amine Michael adduction.
      The greater neurotoxicity of ONE could reflect in part the different reactivity
      characteristics of ONE as compared to HNE.

PMID- 16097796
TI  - Evidence for the formation of adducts and S-(carboxymethyl)cysteine on reaction
      of alpha-dicarbonyl compounds with thiol groups on amino acids, peptides, and
      proteins.
AB  - Nonenzymatic covalent adduction of glucose, or aldehydes derived from glucose or
      oxidation reactions, to proteins (glycation) has been proposed as a key factor in
      the vascular complications of diabetes. In conditions of chronic glucose
      elevation, alpha-dicarbonyl compounds, including glyoxal and methylglyoxal, are
      also present at elevated levels. These carbonyls react rapidly with nucleophilic
      groups on Lys and Arg side chains and the N-terminal amino group, to give poorly
      defined products, often called advanced glycation endproducts. These are present
      at elevated levels in tissue samples from people with diabetes and have been
      linked with disease development. As the thiol group of Cys is a powerful
      nucleophile, we hypothesized that adduction should occur rapidly and efficiently
      at Cys residues. It is shown here that Cys residues react with dicarbonyl
      compounds to give thiol-aldehyde adducts, which have been detected by
      electrospray ionization mass spectrometry. This process is accompanied by loss of
      the thiol group and formation of stable products. In the case of glyoxal, these
      reactions give S-(carboxymethyl)cysteine. The percentage conversion of thiol lost
      to product is substrate-dependent and < or = 32%. S-(Carboxymethyl)cysteine has
      been quantified by HPLC on thiol-containing, protected amino acids, peptides, and
      proteins, after exposure to glyoxal. The yield of this product has been shown to
      increase in a time- and dose-dependent manner with higher glyoxal concentrations
      and to also be formed on extended incubation of serum albumin with glucose. This
      novel, stable, advanced glycation endproduct is a potential marker of glycation.

PMID- 16097797
TI  - Functional, biochemical, and pathological effects of repeated oral administration
      of ochratoxin A to rats.
AB  - Ochratoxin A (OTA), a mycotoxin produced by several fungi of Aspergillus and
      Penicillium species, may contaminate agricultural products, resulting in chronic
      human exposure. In rats, OTA is a potent nephrotoxin, and repeated administration
      of OTA for 2 years to rats in doses up to 0.21 mg/kg of body wt resulted in high
      incidences of renal tumors arising from the proximal tubular epithelial cells.
      The mechanism of tumor formation by OTA in the kidney is not well-defined, and
      controversial results regarding mode of action have been published. The aim of
      this study was to characterize dose-dependent changes induced by OTA by
      application of clinical chemistry, biochemical markers, and toxicokinetics for a
      better conclusion on modes of action. Administration of OTA (0, 0.25, 0.5, 1, and
      2 mg/kg of body wt) to male F344 rats (n = 3 per group) by oral gavage for 2
      weeks resulted in a dose-dependent increase in OTA plasma concentrations and
      concentrations of OTA in both liver and kidney. Although oxidative stress has
      been implicated in OTA carcinogenicity, treatment with OTA did not induce overt
      lipid peroxidation or an increase in 8-oxo-7,8-dihydro-2'deoxyguanosine (8-OH-dG)
      in kidney. In the kidney, OTA-induced pathology was present at all dose levels
      administered, with a clear increase in severity related to dose. Pathology was
      restricted to the outer stripe of the outer medulla and consisted of
      disorganization of the tubule arrangement, frequent apoptotic cells, and
      abnormally enlarged nuclei scattered through the S3 tubules. Consistent with the
      histopathology, a dose-dependent increase in the expression of proliferating cell
      nuclear antigen (PCNA), indicative of cell proliferation, was observed in
      kidneys, but not in livers of treated animals. The most prominent change in the
      composition of urine induced by OTA analyzed by 1H NMR and principal component
      analysis consisted of a major increase in the excretion of trimethylamine N
      oxide. However, typical changes observed with other proximal tubular toxins such
      as increased excretion of glucose were not observed at any of the doses
      administered. Similarly, treatment with OTA had no clear effects on clinical
      chemical parameters indicative of nephrotoxicity, although urinary volume was
      increased at the higher-dose groups. Taken together, the uncommon changes induced
      by OTA suggest that a unique mechanism may be involved in OTA nephrotoxicity and
      carcinogenicity.

PMID- 16097798
TI  - Ochratoxin a causes DNA damage and cytogenetic effects but no DNA adducts in
      rats.
AB  - Ochratoxin A (OTA) is a potent nephrotoxin and renal carcinogen in rats, but the
      mechanism of OTA tumorigenicity is unknown. Ochratoxin A has been shown to be
      negative in many genetic toxicology test in vitro. However, the potential of OTA
      to induce genotoxic effects has not been investigated in male rats, the most
      sensitive species for OTA-induced tumor formation. In this study, male F344 rats
      were repeatedly administered OTA (0, 250, 500, 1000, and 2000 microg/kg of body
      wt) or the non-chlorinated analogue ochratoxin B (OTB; 2000 microg/kg of body wt)
      for 2 weeks (5 days/week), and DNA breakage was analyzed in target and nontarget
      tissues using the comet assay both in the absence and presence of
      formamidopyrimidine-DNA (Fpg) glycosylase. Potential DNA-adduct formation was
      also analyzed in the target organ kidney by 32P-postlabeling using two different
      solvent systems. DNA-strand breaks were evident in liver, kidney, and spleen of
      animals treated with OTA, and a similar degree of DNA damage was observed in rats
      treated with OTB, despite the lower toxicity of OTB. Moreover, the presence of
      DNA damage did not correlate with histopathological alterations, which were
      evident in the kidney but not in the liver. In liver and kidney, the extent of
      DNA damage was further enhanced in the presence of Fpg glycosylase, which is
      known to convert oxidative DNA damage into strand breaks, suggesting the presence
      of oxidative DNA damage. Oxidative DNA damage as a mechanism of OTA-dependent DNA
      damage is consistent with the absence of lipophilic DNA adducts as assessed by
      32P-postlabeling analysis. No spots indicative of OTA-related DNA adducts were
      observed in kidney DNA extracted from OTA-treated animals by 32P-postlabeling
      analysis, despite the use of synthetic standard for postulated adducts. A small,
      but not significant, increase in the incidence of chromosomal aberrations
      (essentially chromatid and chromosome-type deletions) was observed in splenocytes
      from rats treated with OTA in vivo and subsequently cultured in vitro to express
      chromosomal damage. These aberrations are also compatible with oxidative DNA
      lesions since they are not typically caused by chemical carcinogens which form
      covalent DNA adducts. Together, with the lack of evidence for formation of
      lipophilic DNA adducts as assessed by postlabeling, these data suggest that OTA
      may cause genetic damage in both target and nontarget tissues independent of
      direct covalent binding to DNA.

PMID- 16097799
TI  - Effects of naphthalene quinonoids on the induction of oxidative DNA damage and
      cytotoxicity in calf thymus DNA and in human cultured cells.
AB  - The purpose of this study was to examine the differences in the induction of DNA
      damage and cytotoxic effects by quinonoid derivatives of naphthalene in calf
      thymus DNA (ct-DNA) and in human T47D breast cancer cells. Results indicated that
      copper(II) and NADPH were essential for causing oxidant-mediated aldehydic DNA
      lesions (ADLs), including abasic sites and aldehydic base/sugar lesions, in ct
      DNA exposed to 1,2-naphthalenediol (NCAT), 1,4-naphthalenediol (NHQ), 1,2
      naphthoquinone (1,2-NQ), and 1,4-naphthoquinone (1,4-NQ). The ADLs induced by
      naphthalene quinonoids in ct-DNA decrease in the rank order NCAT congruent with
      1,2-NQ > NHQ >> 1,4-NQ. Results from the analyses in cells indicated that after
      1.5-5 h of exposure all naphthalene quinonoids induced a cytotoxic response in
      T47D cells at concentrations 10-100 microM or above, where NHQ and 1,4-NQ were
      approximately 5-10 times more efficient than NCAT and 1,2-NQ in the induction of
      cell death. In addition, NHQ, 1,2-NQ, and 1,4-NQ were not able to produce
      measurable levels of ADLs in cells at concentrations up to 1.25 mM, whereas NCAT
      (0.75-1.25 mM) induced a significant increase in the number of ADLs in T47D cells
      after 1.5 h of exposure when compared to control. The specific type of ADLs
      induced by NCAT is resistant to cellular excision repair pathway. Results from
      the measurements of reactive oxygen species (ROS) indicated that all naphthalene
      quinonoids induced increases in ROS formation in T47D cells. The induction of ROS
      formation in cells by naphthalene quinonoids decreases in the rank order 1,4-NQ
      congruent with 1,2-NQ > NHQ > NCAT. Overall, results from our investigation
      suggest that naphthalene quinonoids cause cell death at concentrations well below
      the concentrations at which they induce the formation of ADLs, perhaps by
      altering intracellular redox status.

PMID- 16097800
TI  - Mutagenesis induced by oxidized DNA precursors: roles of Y family DNA polymerases
      in Escherichia coli.
AB  - To reveal the roles of Y family DNA polymerases in the mutagenesis induced by
      oxidatively damaged DNA precursors, 2-hydroxy-dATP (2-OH-dATP) and 8-hydroxy-dGTP
      (8-OH-dGTP) were introduced into Escherichia coli strains deficient in the Y
      family polymerases, DNA polymerase IV (pol IV, encoded by the dinB gene) and DNA
      polymerase V (pol V, encoded by the umuDC locus). The mutation induced by 2-OH
      dATP, but not that induced by 8-OH-dGTP, occurred less frequently in the dinB-
      strain than in the wild-type (wt) strain, suggesting the involvement of pol IV in
      the mutagenesis by 2-OH-dATP. Expression of pol IV from plasmid enhanced the
      mutagenesis by 2-OH-dATP in the dinB- strain. This enhancement depends on the
      polymerase activity since the expression of a mutant pol IV lacking the
      polymerase activity did not increase the mutations induced by 2-OH-dATP. In
      contrast, both 2-OH-dATP and 8-OH-dGTP caused mutations more efficiently in the
      umuDC- strain than in the wt strain, suggesting that the umuDC gene products
      suppressed the mutagenesis by these oxidized DNA precursors. The DNA polymerase
      activity was not required for the suppressive effects because expression of the
      umuDC gene products lacking the polymerase activity also suppressed the
      mutagenesis. These results suggest that the E. coli pol IV was involved in
      mutagenesis by 2-OH-dATP and that the umuDC gene products play suppressive
      role(s) in the mutagenesis by damaged nucleotides.

PMID- 16097801
TI  - Induction of phenotypes resembling CuZn-superoxide dismutase deletion in wild
      type yeast cells: an in vivo assay for the role of superoxide in the toxicity of
      redox-cycling compounds.
AB  - Yeast (Saccharomyces cerevisiae) lacking the enzyme CuZn-superoxide dismutase
      (sod1delta) display a large number of dioxygen sensitive phenotypes, such as
      amino acid auxotrophies, sensitivity to elevated temperatures, and sensitivity to
      100% dioxygen, which are attributed to superoxide stress. Such cells are
      exquisitely sensitive to small amounts of the herbicide paraquat (methyl
      viologen), which is known to produce high fluxes of superoxide in vivo via a
      redox-cycling mechanism. We report that dioxygen sensitive phenotypes similar to
      those seen in sod1delta cells can be induced in wild-type cells by treatment with
      moderate concentrations of paraquat or diquat, another bipyridyl herbicide,
      providing strong evidence that the mechanism of toxicity for both of these
      compounds is attributable to superoxide stress. Certain redox-cycling quinone
      compounds (e.g., menadione and plumbagin) are also far more toxic toward
      sod1delta than to wild type. However, treatment of wild-type yeast with menadione
      or plumbagin did not induce sod1delta-like phenotypes, although toxicity was
      evident. Thus, their toxicity in wild type cells is predominantly, but not
      exclusively, due to mechanisms unrelated to superoxide production. Further
      evidence for a different basis of toxicity toward wild-type yeast in these two
      classes of redox-cycling compounds includes the observations that (i) growth in
      low oxygen alleviated the effects of paraquat and diquat but not those of
      menadione or plumbagin and (ii) activity of the superoxide sensitive enzyme
      aconitase is affected by very low concentrations of paraquat but only by higher,
      growth inhibitory concentrations of menadione. These results provide the basis
      for an easy qualitative assay of the contribution of redox-cycling to the
      toxicity of a test compound. Using this method, we analyzed the Parkinsonism
      inducing compound 1-methyl-4-phenylpyridinium and found that redox cycling and
      superoxide toxicity are not the predominant factor in its toxic mechanism.

PMID- 16097802
TI  - Interactions of sodium selenite, glutathione, arsenic species, and omega class
      human glutathione transferase.
AB  - Human monomethylarsenate reductase [MMA(V) reductase] and human glutathione S
      transferase omega 1-1 (hGSTO1-1) [because MMA(V) reductase and hGSTO1-1 are
      identical proteins, the authors will utilize the designation "hGSTO1-1"] are
      identical proteins that catalyze the reduction of arsenate, monomethylarsenate
      [MMA(V)], and dimethylarsenate [DMA(V)]. Sodium selenite (selenite) inhibited the
      reduction of each of these substrates by the enzyme in a concentration-dependent
      manner. The kinetics indicated a noncompetitive inhibition of the MMA(V), DMA(V),
      or arsenate reducing activity of hGSTO1-1. The inhibition of the MMA(V) reducting
      activity of hGSTO1-1 by selenite was reversed by 1 mM DL-dithiothreitol (DTT) but
      not by reduced glutathione (GSH), which is a required substrate for the enzyme.
      Neither superoxide anion nor hydrogen peroxide was involved in the selenite
      inhibition of hGSTO1-1. MALDI-TOF and MS/MS analysis demonstrated that five
      molecules of GSH were bound to one monomer of hGSTO1-1. Four of the five
      cysteines of the monomer were glutathionylated. Cys-32 in the active center,
      however, exists mostly in the sulfhydryl form since it was alkylated consistently
      by iodoacetamide. MALDI-TOF mass spectra analysis of hGSTO1-1 after reaction with
      GSH and sodium selenite indicated that selenium was integrated into hGSTO1-1
      molecules. Three selenium were found to be covalently bonded to the monomer of
      hGSTO1-1 with three molecules of GSH. It is proposed that the reaction products
      of the reduction of selenite inhibited the activity of hGSTO1-1 by reacting with
      disulfides of glutathionylated cysteines to form bis (S-cysteinyl)selenide and S
      selanylcysteine and had little or no interaction with the sulfhydryl of Cys-32 in
      the active site of the enzyme.

PMID- 16097803
TI  - Xanthohumol isolated from Humulus lupulus Inhibits menadione-induced DNA damage
      through induction of quinone reductase.
AB  - The female parts of hops (Humulus lupulus L.) show estrogenic effects as well as
      cancer chemopreventive potential. We analyzed the chemopreventive mechanism of
      hops by studying its antioxidative activities and its effect on the
      detoxification of a potentially toxic quinone (menadione). The detoxification
      enzyme quinone reductase [(NAD(P)H:quinone oxidoreductase, QR] protects against
      quinone-induced toxicity and has been used as a marker in cancer chemoprevention
      studies. Although the hop extract was only a weak quencher of free radicals
      formed from 1,1-diphenyl-2-picrylhydrazyl, it demonstrated strong QR induction in
      Hepa 1c1c7 cells. In addition, compounds isolated from hops including xanthohumol
      (XH) and 8-prenylnaringenin were tested for QR induction. Among these, XH was the
      most effective at inducing QR with a concentration required to double the
      specific activity of QR (CD value) of 1.7 +/- 0.7 microM. In addition,
      pretreatment of Hepa1c1c7 cells with XH significantly inhibited menadione-induced
      DNA single-strand breaks. The QR inhibitor dicumarol reversed the protective
      effect of XH against menadione-induced DNA damage. Because the expression of QR
      and other detoxifying enzymes is known to be upregulated by binding of the
      transcription factor Nrf2 to the antioxidant response element (ARE), the reporter
      activity mediated by ARE in HepG2-ARE-C8 cells was investigated after incubation
      with XH for 24 h. Under these conditions, XH increased ARE reporter activity in a
      dose-dependent manner. One mechanism by which XH might induce QR could be through
      interaction with Keap1, which sequesters Nrf2 in the cytoplasm, so that it cannot
      activate the ARE. Using LC-MS-MS, we demonstrated that XH alkylates human Keap1
      protein, most likely on a subset of the 27 cysteines of Keap1. This suggests that
      XH induces QR by covalently modifying the Keap1 protein. Therefore, XH and hops
      dietary supplements might function as chemopreventive agents, through induction
      of detoxification enzymes such as QR.

PMID- 16097804
TI  - High-performance liquid chromatography electrospray ionization tandem mass
      spectrometry for the detection and quantitation of benzo[a]pyrene-DNA adducts.
AB  - A method, using HPLC combined with electrospray tandem mass spectrometry (ES
      MS/MS), was developed and validated to detect and quantify the major DNA adduct
      resulting from exposure to the ultimate tumorigenic benzo[a]pyrene (BP)
      metabolite, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene
      (BPDE). Calf thymus DNA was reacted with BPDE, digested enzymatically to
      nucleosides, and the major DNA adduct, 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy
      7,8,9,10-tetrahydrobenzo[a]pyrene (dG-BPDE), was purified by HPLC. Similar
      procedures were applied to prepare dG-BPDE-d8 from [1,2,3,4,5,6,11,12-(2)H8]BPDE
      for use as an internal standard. The HPLC-ES-MS/MS method was validated using a
      mixture of hydrolyzed salmon testis DNA (82 microg) and 10 pg dG-BPDE (analogous
      to 6.9 adducts/10(8) nucleotides). The results indicated an inter- and intraday
      accuracy of 99-100% and precision of 1.6-1.7% (relative standard deviation). When
      applied to a calf thymus DNA sample modified in vitro with [1,3-(3)H]BPDE, the
      method gave a value very similar to those obtained by radiolabeling, (32)P
      postlabeling, and immunoassay. HPLC-ES-MS/MS analysis of hepatic DNA from mice
      treated intraperitoneally with 0.5 and 1.0 mg of [7,8-(3)H]BP gave values
      comparable to those determined by 32P-postlabeling and immunoassay. Lung DNA from
      mice fed a 0.3% coal tar diet (containing approximately 2 mg BP/g coal tar) for
      one month had 0.6 +/- 0.04 dG-BPDE adducts/10(8) nucleotides. This value is much
      lower than the 102 +/- 14 total DNA adducts/10(8) nucleotides determined by 32P
      postlabeling, which suggests that dG-BPDE makes only a minor contribution to the
      DNA adducts formed in lung tissue of mice administered coal tar. The HPLC-ES
      MS/MS method was used to assess human lung DNA samples for the presence of dG
      BPDE. Based upon a limit of detection of 0.3 dG-BPDE adducts/10(8) nucleotides,
      when using 100 microg of DNA, dG-BPDE was detected in only 1 out of 26 samples.
      These observations indicate that HPLC-ES-MS/MS is suitable to assess the
      contribution of BP to DNA damage caused by exposures to polycyclic aromatic
      hydrocarbon (PAH) mixtures. The results further suggest that dG-BPDE may
      contribute only a small fraction of the total DNA adducts detected by other DNA
      adduct methodologies in individuals exposed to PAHs.

PMID- 16097805
TI  - Reaction of 1,2,3,4-diepoxybutane with 2'-deoxyguanosine: initial products and
      their stabilities and decomposition patterns under physiological conditions.
AB  - 1,2,3,4-Diepoxybutane (DEB), an in vivo metabolite of 1,3-butadiene (BD), is a
      carcinogen and a potent mutagen. Previously, DEB was shown to react with 2'
      deoxyguanosine (dG) under physiological conditions to produce seven major
      nucleoside adducts resulting from alkylation at the N1- (P8 and P9), N7- (P5 and
      P5'), and both the N1- and the N2-positions of dG to form six-membered (P4-1 and
      P4-2) and seven-membered fused ring systems (P6), respectively [Zhang, X.-Y., and
      Elfarra, A. A. (2003) Chem. Res. Toxicol. 16, 1606. Zhang, X.-Y., and Elfarra, A.
      A. (2004) Chem. Res. Toxicol. 17, 521]. In the present study, the stabilities and
      decomposition products of the seven adducts under in vitro physiological
      conditions (phosphate buffer containing KCl, pH 7.4, 37 degrees C) were
      investigated. The results showed that P4-1, P4-2, and P6 were stable, whereas P5,
      P5', P8, and P9 were labile with half-lives of 2.6, 2.7, 16, and 16 h,
      respectively. P5 and P5' decomposed initially by the loss of the deoxyribose
      moiety to yield the corresponding guanine adduct P5D, which exhibited a half-life
      of 33 h and decomposed through opening of the remaining oxirane ring by
      dihydrogen phosphate ion, water, or chloride ion. Decomposition of P8 yielded P4
      1, P6, and nucleoside products resulting from opening of the oxirane ring by
      dihydrogen phosphate ion, water, or chloride ion. Similarly, decomposition of P9
      led to the formation of P4-2, P6, and nucleoside products resulting from opening
      of the oxirane ring by dihydrogen phosphate ion, water, or chloride ion. These
      results indicate that the initial products of the reaction of DEB with dG are P5,
      P5', P8, and P9, whereas P4-1, P4-2, and P6 are secondary products. The results
      may also facilitate development of useful biomarkers of exposure to DEB.

PMID- 16097806
TI  - Cysteine modification by lipid peroxidation products inhibits protein disulfide
      isomerase.
AB  - A proteomic approach was applied to mitochondrial protein isolated from the
      livers of rats fed a combination high-fat and ethanol diet to identify proteins
      modified by 4-hydroxynonenal (4-HNE). Using this approach, the endoplasmic
      reticulum chaperone, protein disulfide isomerase (PDI), which participates in the
      maturation of newly synthesized proteins through promoting correct disulfide
      formation, was consistently found to be modified by 4-HNE. Further mass spectral
      analysis of PDI isolated from the animals revealed modification of an active site
      Cys residue thought to be involved in client protein binding. To test the
      hypothesis that 4-HNE inhibits the chaperone, purified bovine PDI was treated
      with concentrations of 4-HNE ranging from 20 to 200 microM (10-100-fold molar
      excess aldehyde), resulting in 14-56% inhibition, respectively. Similar
      treatments with the lipid peroxidation products acrolein (ACR) and 4-oxononenal
      (4-ONE) resulted in 60 and 100% inhibition, respectively, suggesting inactivation
      of the chaperone via Cys modification. Thiol sensitivity was confirmed through
      concentration-dependent inhibition of PDI by the Cys modifier N-ethylmaleimide
      (NEM). While some degree of sensitivity to these lipid aldehydes is suggested by
      the data, when compared to inactivation of other proteins by 4-HNE, PDI has
      demonstrated a relative resistance. It was also observed that physiologic (e.g.,
      4 mM) concentrations of GSH were capable of removing the 4-HNE adducts, likely
      serving as a protective mechanism against inactivation by 4-HNE and other lipid
      peroxidation products. However, because an active site Cys was found to be
      modified by 4-HNE on PDI in vivo, it is possible that the protective effect of
      GSH on the chaperone decreases under conditions of sustained oxidative stress,
      such as during chronic alcohol consumption, as GSH is depleted. The data
      presented here thus suggest potential impairment of an important molecular
      chaperone during oxidative stress.

PMID- 16097807
TI  - Oxidation of 5-hydroxypyrimidine nucleosides to 5-hydroxyhydantoin and its alpha
      hydroxy-ketone isomer.
AB  - The reaction of hydroxyl radicals with 2'-deoxycytidine (dCyd), as well as the
      decomposition of dCyd radical cations, leads to a complex mixture of oxidation
      products in aqueous aerated solutions. The oxidation of dCyd gives products with
      a relatively low oxidation potential that are highly susceptible to further
      oxidation, including 5-hydroxy-2'-deoxycytidine (5-oh-dCyd) and 5-hydroxy-2'
      deoxyuridine (5-oh-dUrd). Previously, we showed that the oxidation of 2'
      deoxyuridine (dUrd) involves the formation of dialuric acid and isodialuric acid
      intermediates, followed by ring contraction to N1-(2-deoxy-beta-D-erythro
      pentofuranosyl)-5-hydroxyhydantoin (5-oh-dHyd). In this work, we have examined
      the oxidation of 5-oh-dCyd and 5-oh-dUrd in greater detail. The oxidation of
      these substrates by Br2 led to a similar profile of intermediate and stable
      products indicating that the dialuric and isodialuric acid derivatives of dCyd
      largely undergo deamination before they transform into 5-oh-dHyd. Analysis of the
      final mixture of oxidation products by HPLC revealed the formation of two novel
      products. On the basis of NMR and MS, these products were identified as the
      diastereomers of N1-(2-deoxy-beta-D-erythro-pentofuranosyl)-5
      hydroxyimidazolidine-2,5-dione (iso-4-oh-dHyd). These products arise from alpha
      hydroxy-ketone isomerization of 5-oh-dHyd. The isomerization of 5-oh-dHyd to iso
      4-oh-dHyd was reversible, and each diastereomer produced a specific diastereomer
      of the other structural isomer. The rate of isomerization was accelerated in
      going from pH 5 to pH 9, whereas all isomers decomposed at higher pH. In
      contrast, interconversion between each pair of diastereomers was minor. Thus, we
      conclude that the oxidation of 5-oh-dCyd or 5-oh-dUrd gives a mixture of four
      isomers of 5-oh-dHyd and iso-4-oh-dHyd as final products. The biological
      consequences of dCyd oxidation may ultimately depend on the effects of these
      products.

PMID- 16097808
TI  - Synthesis and coordination chemistry of a photoswitchable bis(phosphine) ligand.
AB  - A 1,2-dithienylethene compound bearing bis(phosphine) groups (1o) represents a
      new class of photoresponsive ligands where there are steric and electronic
      differences between two photogenerated isomers. The coordination chemistry of
      this ligand class is demonstrated by preparing a gold(I) complex (2o) and a
      phosphine selenide (3o).

PMID- 16097809
TI  - Lanthanide-potassium wheels.
AB  - Mixed potassium-lanthanide wheel-shaped-structured, hexanuclear coordination
      oligomers of composition [(eta5-C5H5)Ln(NPh2)2{N(PPh2)2}2K2(THF)4]2 (Ln = Er
      (1a), Yb (1b)) and an octanuclear coordination polymer of composition [(eta5
      C5H5)Sm(NPh2)2{N(PPh2)2}K]infinity (2) were synthesized. All presented compounds
      can be obtained in moderate yields in a one-pot procedure, in which the potassium
      salts KNPh2 and [K(THF)(n)N(PPh2)2] as well as NaC5H5 are reacted with anhydrous
      samarium, erbium, and ytterbium trichloride in THF.

PMID- 16097810
TI  - Observation of electroluminescence at room temperature from a ruthenium(II) bis
      terpyridine complex and its use for preparing light-emitting electrochemical
      cells.
AB  - A terpyridine ruthenium (II) complex containing a substituted and an
      unsubstituted terpyridine ligand was synthesized, and its luminescence properties
      were studied in a solid-state single-layer light-emitting electrochemical cell.
      The obtained devices emitted light of a very deep red color (CIE, x = 0.717 y =
      0.282) at low external applied bias. It is the first example of an
      electroluminescence device based on a bis-chelated ruthenium complex. Its ambient
      atmosphere decay is remarkably different from analogous devices using tris
      chelated ruthenium complexes.

PMID- 16097811
TI  - Cyano-bridged Mn(III)3M(III) (M(III) = Fe, Cr) complexes: synthesis, structure,
      and magnetic properties.
AB  - Two cyano-bridged tetranuclear complexes composed of Mn(III) salen (salen = N,N'
      ethylene bis(salicylideneiminate)) and hexacyanometalate(III) (M = Fe, Cr) in a
      stoichiometry of 3:1 have been selectively synthesized using {NH2(n
      C12H25)2}3[M(III)(CN)6] (M(III) = Fe, Cr) starting materials:
      [{Mn(salen)(EtOH)}3{M(CN)6}] (M = Fe, 1; Cr, 2). Compounds 1 and 2 are
      isostructural with a T-shaped structure, in which [M(CN)6]3- assumes a meridional
      tridentate building block to bind three [Mn(salen)(EtOH)]+ units. The strong
      frequency dependence and observation of hysteresis on the field dependence of the
      magnetization indicate that 1 is a single-molecule magnet.

PMID- 16097812
TI  - Synthesis and structural characterization of a nonplanar neutral [36]metallacrown
      12 nickel compound [Ni(C13H9N3O2)(CH3OH)]12.
AB  - A nonplanar metallacrown [Ni-N-N]12 was achieved using a pentadente ligand,
      salicylaldehyde 2-pyridinecarboxylhydrazone (H2L) via a new modular self-assembly
      approach. The special bridging models of the ligand forced the macrocycle to form
      in a specific size with the wavelike conformation.

PMID- 16097813
TI  - Simple route to the doubly ortho-palladated azobenzenes: building blocks for
      organometallic polymers and metallomesogens.
AB  - A new class of doubly cyclopalladated complexes, {PdCl(dmf)}2(mu-azb) (1) and
      {PdCl(dmf)}2(mu-aazb) (2), has been prepared in dimethylformamide (dmf) by
      reaction of azobenzene (azb) and 4-aminoazobenzene (aazb), respectively, with an
      excess of PdCl2(CH3CN)2 complex. Recrystallization of 1 and 2 in dimethyl
      sulfoxide (dmso) yields complexes {PdCl(dmso)}2(mu-azb) (3) and {PdCl(dmso)}2(mu
      aazb) (4), respectively. The crystal structures of 1 and 4 have been determined
      by X-ray diffraction. All complexes are characterized by 1H and 13C NMR spectra
      and elemental analysis. In both crystal structures, solvent molecules are bound
      to palladium through oxygen atoms and oriented trans to carbon. In view of
      greater preference of palladium to nitrogen and sulfur atoms, the experimental
      structures were rationalized by quantum-chemical calculations and confirmed as
      the most stable isomers.

PMID- 16097814
TI  - Novel self-assembled chain of water molecules in a metal-organic framework
      structure of Co(II) with tartrate acid.
AB  - 1-D water chains constructed by dimer water clusters and edge-sharing cyclic
      pentamer have been observed in the compound [Co(C4H4O6)(2,2'-bipy) x 5H2O] (1),
      in which the water chains join the 1-D coordination polymeric chains to a 3-D
      network through hydrogen-bond interactions.

PMID- 16097815
TI  - Isolated magnetic clusters of Co(II) and Ni(II) within 3-dimensional organic
      frameworks of 6-mercaptonicotinic acid: unique structural topologies based on
      selectivity for hard and soft coordination environments.
AB  - Hydrothermal reaction of the mixed thiolate-carboxylate-aromatic amine ligand, 6
      mercaptonicotinic acid (6-mnaH2) with Co(II) and Ni(II) leads to two network
      coordination solids [M9(6-mna)8(mu3-O)2(OH3)2(OH2)6] (M = Co, Ni), 1, and
      [M2Ni12(6-mna)12(mu3-OH)2(OH2)6] x 8H2O (M = K, Rb, Cs), 2. These compounds are
      unusual for two reasons: they are thiolate-bridged networks and they are three
      dimensional lattices which contain isolated metal clusters and chains. The
      magnetic behavior of these compounds has been studied, showing that 2 contains
      ferromagnetically coupled Ni6 wheels.

PMID- 16097816
TI  - 2,2';9',2''-Ter[1,10]phenanthroline.
AB  - The title molecule, 2,2';9',2''-ter[1,10]phenanthroline can be prepared from 2,9
      dichloro-1,10-phenanthroline in three steps through the corresponding diacetyl
      intermediate. The ligand acts as a hexadentate with K+, while two molecules form
      a trinuclear, helical complex with Cu(I), which evidences pi-stacking
      interactions and Cu-Cu distances of 3.01-3.04 A. Electrochemical analysis shows a
      strong interaction between the Cu(I) centers.

PMID- 16097817
TI  - Squeezing the [Cu-OH...H2O-Cu]3+ bridge by cryptate encapsulation.
AB  - Treatment of cryptand L(1) with Cu(II) generates a H3O2(-)-bridged dicopper(II)
      cryptate, 2, where the guest anion has responded to steric constraint by a
      significant shortening of the O-O distance to 2.325(9) A; computational
      optimization at the B3LYP/6-31(d) level suggests that the bridging O-H...O H-bond
      is bent (approximately 157 degrees) but that the barrier to interchange of the
      bridging H atom is low (<4 kJ mol(-1)). This cryptate, rather than the
      [Cu2L(1)muCN]3+ species recently claimed to derive from cleavage of the C-C bond
      of the solvent, is the product of acetonitrile recrystallization of the initially
      formed reaction product, 1.

PMID- 16097818
TI  - A5InPb8 (A = K, Rb): an apparent zintl phase with lead tetrahedra interbridged by
      mu6-In atoms.
AB  - Reaction of elemental In, Pb, and K, or Rb within welded Ta containers at 900
      degrees C followed by subsequent annealing at 350 degrees C gives the new phases
      A5InPb8 (A = K, Rb). These crystallize in the trigonal space group R3m (No. 166,
      Z = 3) with cell dimensions of a = 6.8835(6) and 6.885(1) A and c = 37.591(5) and
      37.64(2) A for K5InPb8 and Rb5InPb8, respectively. The structure contains
      clusters built of pairs of Pb4 tetrahedra that are interbridged by a mu6-In atom.
      The InPb8 units, which in the isolated case would behave as ideal 40-electron
      Wade's rule clusters, are weakly interlinked into sheets in the ab plane by long
      (3.5 A) intercluster Pb-Pb interactions. According to the EHTB calculations,
      these cause a broadening of the valence band and thus generate a number of new
      states at the Fermi level. Compound K5InPb8 is metallic (rho298 approximately 42
      microohms cm, (delta rho/delta T)/rho approximately 1.4(2) x 10(-1) K(-1)) which
      is in agreement with the expectations according to calculations on the anion
      network.

PMID- 16097819
TI  - Ruthenium(II) complexes of 1,12-diazaperylene and their interactions with DNA.
AB  - Four complexes of the ligand 1,12-diazaperylene (DAP) have been prepared,
      [Ru(bpy)n(DAP)(3-n)]2+ where n = 0-2 and [Ru(DAP)3]2+. The [Ru(DAP)3]2+ complex
      was characterized by X-ray analysis and was found to exhibit the expected
      propeller-like structure with significant intermolecular pi-stacking
      interactions. The three Ru(II) complexes showed self-consistent optoelectronic
      properties with similar ligand-centered pi-pi* absorptions in the range of 333
      468 nm and MLCT bands associated with the DAP which increased in intensity and
      decreased in energy as the number of DAP ligands varied from 1 to 3.
      Hypochromicity and viscosity changes were observed that were consistent with DAP
      intercalation into DNA, and binding constants were measured in the range of 1.4
      1.6 x 10(6) M(-1) for the mixed ligand complexes. Furthermore, the complex
      [Ru(bpy)2(DAP)]2+ was found to photocleave plasmid DNA upon irradiation with
      visible light.

PMID- 16097820
TI  - Crystal structures and magnetic properties of complexes of M(II)Cl2 (M = Cu, Ni,
      and Co) coordinated with 4-(N-tert-butyloxyamino)-2-(methoxymethylenyl)pyridine:
      2D magnetic anisotropy of the aminoxyl-Co(II) complex in the crystalline state.
AB  - Three metal complexes, [M(II)Cl2(4NOPy-OMe)2] (M = Cu (1), Ni (2), and Co (3)),
      were prepared by mixing the corresponding metal chloride and 4-(N-tert
      butyloxyamino)-2-(methoxymethylenyl)pyridine, 4NOPy-OMe, in 1:2 ratio. Complex 1
      has two structures (complexes A and B) with similar coordination geometries,
      compressed octahedrons. In the crystal structure, complexes A and B locate
      alternately in short distances (C(radical)...C(beta) = 3.17 and 3.23 A) to form a
      1-D chain structure. Complexes 2 and 3 are isomorphous and have a slightly
      distorted octahedral structure. In the crystal structure, both complexes have
      intermolecular short contacts (C(radical)...C(alpha) = 3.46 and 3.52 A for 2 and
      3, respectively) to form the 2-D structures. The temperature dependence of the
      chi(mol)T values for the three complexes indicated that the magnetic interactions
      between the radicals and the metal ions within the complexes were ferromagnetic.
      By fitting a modified Fisher 1-D model to the data of the chi(mol)T vs T plot for
      1, we estimated the intra- and intermolecular (intrachain) exchange coupling
      constants to be J1/kB = 60.2 and J2/kB = -7.02 K, respectively. On the other
      hand, complexes 2 and 3 showed steep increases of the chi(mol)T value below ca. 3
      K, indicating that the long-range magnetic ordering is operating. The 1/chi(mol)
      vs T plot for 2 was analyzed by a Curie-Weiss model to give theta = 6.25 K and C
      = 2.02 cm3 K mol(-1) with g(Ni) = 2.25. Complex 3 was investigated in more detail
      using an orientated sample. Magnetic behavior strongly depends on the direction
      of the applied field, in which the c axis perpendicular to the ab plane is an
      easy axis for magnetization. Direct current (dc) and alternating current (ac)
      magnetic susceptibility measurements revealed that complex 3 had a magnetic phase
      transition of T(c) = 2.14 K and exhibited a glasslike magnetic behavior below
      T(c).

PMID- 16097821
TI  - A family of Au-Tl loosely bound butterfly clusters.
AB  - By treatment of the polymeric species [AuTl(C6Cl5)2]n with ketones or with
      acetylacetone and 4,4'-bipyridine, the new tetranuclear complexes
      [Au2Tl2(C6Cl5)4] x L (L = PhMeC=O, acacH) or [Au2Tl2(C6Cl5)4(bipy)] x (acacH)
      have been prepared. Their crystal structures have been determined by X-ray
      diffraction methods and they all present a central Au2Tl2 core formed via one
      Tl...Tl and four Au...Tl unsupported interactions resulting in a loosely bound
      butterfly cluster. These complexes are strongly luminescent in both the solid
      state and solution showing an optical behavior in agreement with the maintenance
      of the Tl...Tl contact even in solution.

PMID- 16097822
TI  - Solid-state structures and magnetic properties of halide-bridged, face-to-face
      bis-nickel(II)-macrocyclic ligand complexes: ligand-mediated interchanges of
      electronic configuration.
AB  - Dramatic differences are found between the ambient and 100 K X-ray structures of
      [L(2)Ni2Br2](ClO4)2 (L(2) = alpha,alpha'-bis{(5,7-dimethyl-1,4,8,11
      tetraazacyclotetradeca-6-yl)-o-xylene), in which the bromide-bridged, bimetallic,
      macrocyclic ligand complexes of nickel(II) are held face-to-face and in which
      each bimetallic complex has a net triplet spin multiplicity. The ambient
      structure of this complex consists of very highly ordered, infinite chains of
      alternating R and S isomers in which the identical Ni(II) coordination spheres
      are near to the average expected for the high- and low-spin Ni(II) coordination
      sites, and there is appreciable stereochemical strain in the linkage of the
      macrocyclic ligands to the phenyl ring. In contrast, every other dinickel complex
      of the 100 K structure is displaced about 40 pm along the infinite chains to form
      tetrameric repeat units (pairs of dinickel complexes), in which each dinickel
      complex has well-defined high-spin and low-spin Ni(II) coordination sites; the
      high-spin sites are adjacent in the tetramers, and the stereochemical strain in
      the linkage to the phenyl spacer is relaxed. The molecular magnetic moments and
      structural contrasts are similar for the 100 K structure and the previously
      reported ambient structure of [L(2)Ni2Br3](ClO4) complex for which the molecular
      magnetic moments also correspond to a single triplet state per complex. The
      halide-bridged, monochloro- and monobromo dinickel complexes also have triplet
      spin multiplicity, and they crystallize with a coordinated perchlorate completing
      the axial coordination of the high-spin Ni(II) site, while the other Ni(II) site
      of these halide-bridged complexes has equatorial Ni-N bond lengths typical of low
      spin Ni(II) coordination. The bridging halide is sandwiched between the face-to
      face macrocyclic ligand Ni(II) moieties and slightly off the Ni-Ni axis in all of
      the complexes. The temperature dependence of the magnetic moments of the series
      of complexes indicates that their singlet-triplet energy gaps are small, with
      zero point energy differences that are generally less than 10(3) cm(-1). The very
      weak metal-metal electronic coupling, the triplet state spin multiplicity of each
      dinickel complex, and the averaged high-spin/low-spin coordination environments
      of the ambient structure implicate a vibronic mechanism for the electronic
      configurational exchange in the dibromo and tribromo complexes. The single
      molecular vibrational mode that correlates with the configurational exchange in
      these complexes includes the concerted motion of the bridging bromide between the
      Ni(II) centers. Activation of this vibrational mode is sufficient to effect the
      configurational exchange. These complexes present especially clear examples of
      the effects of the coupling of nuclear vibrational motions to the interchange of
      electronic configuration between two different centers.

PMID- 16097823
TI  - Sulfido-bridged dinuclear molybdenum-copper complexes related to the active site
      of CO dehydrogenase: [(dithiolate)Mo(O)S2Cu(SAr)]2- (dithiolate = 1,2-S2C6H4, 1,2
      S2C6H2-3,6-Cl2, 1,2-S2C2H4).
AB  - The [MoCu] carbon monoxide dehydrogenase (CODH) is a Cu-containing molybdo
      flavoprotein, the active site of which contains a pterin-dithiolene cofactor
      bound to a sulfido-bridged dinuclear Mo-Cu complex. In this paper, the synthesis
      and characterization of dinuclear Mo-Cu complexes relevant to the active site of
      [MoCu]-CODH are described. Reaction of [MoO2S2]2- with CuCN affords the dinuclear
      complex [O2MoS2Cu(CN)]2- (1), in which the CN- ligand can be replaced with
      various aryl thiolates to give rise to a series of dinuclear complexes
      [O2MoS2Cu(SAr)]2- (Ar = Ph (2), o-Tol (3), and p-Tol (4)). An alternative
      synthesis of complex 2 is the reaction of [MoO2S2]2- with [Cu(SPh)3]2-.
      Similarly, [O2MoS2Cu(PPh3)]- (5), [O2MoS2Cu(dppe)]- (dppe = 1,2
      bis(diphenylphosphino)ethane) (6), and [O2MoS2Cu(triphos)]- (triphos = 1,1,1
      tris[(diphenylphosphino)methyl]ethane) (7) were prepared from the reactions of
      [MoO2S2]2- with the Cu(I) phosphine complexes. Treatment of 1, 2, 4, or 5 with
      dithiols (1,2-(SH)2C6H4, 1,2-(SH)2C6H2-3,6-Cl2, and 1,2-(SH)2C2H4), in
      acetonitrile, leads to the replacement of a molybdenum-bound oxo ligand to yield
      [(dithiolate)Mo(O)S2CuL]2- (L = CN, SAr; dithiolate = 1,2-S2C6H4, 1,2-S2C6H2-3,6
      Cl2, or 1,2-S2C2H4) (8-13) or [(1,2-S2C6H4)Mo(O)S2Cu(PPh3)]- (14) complexes.

PMID- 16097824
TI  - Cyclopalladation of the indole ring in palladium(II) complexes of 2N1O-donor
      ligands and its dependence on the O-donor properties.
AB  - Synthetic, structural, spectroscopic, and kinetic studies have been carried out
      on the Pd(II) complexes of new 2N1O-donor ligands containing a pendent indole, 3
      (N-2-pyridylmethyl-N-2-hydroxy-5-methoxybenzylamino)ethylindole (HMeO-iepp), 3-(N
      2-pyridylmethyl-N-2-hydroxy-5-nitrobenzylamino)ethylindole (HNO2-iepp), and (N-2
      pyridylmethyl-3-indolylethylamino)acetic acid (Hiepc) (H denotes a dissociable
      proton). [Pd(MeO-iepp)Cl] (2), [Pd(NO2-iepp)Cl] (3), and [Pd(iepc)Cl] (4) were
      prepared and revealed by X-ray analysis to have a pyridine nitrogen, an amine
      nitrogen, a phenolate or carboxylate oxygen, and a chloride ion in the
      coordination plane. UV absorption and 1H NMR spectral changes indicated that all
      the complexes could be converted to the indole-binding complexes where the O
      donor was replaced by the indole C2 atom by cyclopalladation in DMSO or DMF in
      the temperature range of 40-60 degrees C. Formation of the indole-binding complex
      species obeyed the first-order kinetics, from which the activation parameters
      were estimated. The formation rate was dependent on the properties of the O-donor
      group, a lower pKa value of its conjugate acid causing faster conversion to the
      indole-binding species in the order 2 (methoxyphenolate) < 3 (nitrophenolate) < 4
      (carboxylate). On the other hand, the ratio of the indole-binding complex to the
      O-donor complex as a result of the conversion was greater for the complexes with
      a higher pKa value of the ligand OH group, the order being 2 > 3 > 4.

PMID- 16097825
TI  - Europium(II) and ytterbium(II) cyclic organohydroborates with agostic
      interactions.
AB  - The divalent lanthanide bis((cyclooctane-1,5-diyl)dihydroborate) complexes
      {K(THF)4}2{Ln{(mu-H)2BC8H14}4} (Ln = Eu, 3; Yb, 4) were prepared by a metathesis
      reaction between (THF)(x)LnCl2 and K[H2BC8H14] in THF in a 1:4 molar ratio.
      Although the reaction ratios were varied between 1:3 and 1:6, complexes 3 and 4
      were the only lanthanide 9-BBN hydroborates produced. Because of disorder of THF
      in crystals of 3 and 4, good single-crystal X-ray structural data could not be
      obtained. However, when the potassium cation was replaced by the
      tetramethylammonium cation or when MeTHF (2-methyltetrahydrofuran) was employed
      in place of THF, good quality crystals were obtained. Complexes [NMe4]2[Ln{(mu
      H)2BC8H14}4] (Ln = Eu, 5; Yb, 6) were afforded by metathesis reactions of NMe4Cl
      with 3 and 4 in situ. On the basis of the single-crystal X-ray diffraction
      analysis, the four 9-BBN tetrahydroborate ligands are tetrahedrally arranged
      around the lanthanide cation in 5 and 6. The two structures differ in that one
      alpha-C-H bond from each of the four {(mu-H)2BC8H14}4 units exhibits an agostic
      interaction with Eu(II) in 5 but, in complex 6, only two of the alpha-C-H bonds
      form agostic interactions with Yb(II). Complexes {K(MeTHF)3}2{Ln{(mu-H)2BC8H14}4}
      (Ln = Eu, 7; Yb, 8) were produced by employing MeTHF in place of THF. The
      structures of 7 and 8 display connectivity between the anion {Ln{(mu
      H)2BC8H14}4}2- and the cation {K(MeTHF)3}+, in which the potassium not only
      interacts directly with the hydrogens of the Ln-H-B bridged bonds but is also
      involved in agostic interactions with alpha-C-H bonds. By systematically
      examining the structures of complexes 3-8 and taking into account the previously
      reported complexes (THF)4Ln{(mu-H)2BC8H14}2 (Ln = Eu, 1; Yb, 2), it is concluded
      that Eu(II) appears to have a better ability to form agostic interactions than
      Yb(II) because of its larger size, even though Yb(II) has a higher positive
      charge density.

PMID- 16097826
TI  - Self-assembly of a series of extended architectures based on polyoxometalate
      clusters and silver coordination complexes.
AB  - Three unusual compounds based on polyoxometalate building blocks,
      [(H2O)5Na2(C6NO2H4)(C6NO2H5)3Ag2][Ag2IMo6O24(H2O)4] x 6.25H2O (1),
      [(H2O)4Na2(C6NO2H5)6Ag3][IMo6O24] x 6H2O (2), and
      (C6NO2H6)2[(C6NO2H5)2Ag][Cr(OH)6Mo6O18] x 4H2O (3), have been synthesized and
      characterized by elemental analysis; IR, XPS, and ESR spectroscopy; TG analysis;
      and single-crystal X-ray diffraction. Compound 1 is constructed from the cationic
      two-dimensional (2D) coordination polymer sheets which are constituted of
      [(H2O)5Na2(C6NO2H4)(C6NO2H5)3Ag2]3+ and anionic [Ag2IMo6O24(H2O)4]3- chains as
      pillars, forming a three-dimensional (3D) supramolecular framework via weak Ag-O
      interactions. Compound 2 is composed of the well-defined [IMo6O24]5- building
      blocks, which are linked through trinuclear Ag-pyridine-3-carboxylic acid,
      [(C6NO2H5)6Ag3]3+, fragments into a one-dimensional (1D) hybrid chain; adjacent
      chains are further connected by sodium cations to yield a novel 2D network.
      Compound 3 has a 1D chainlike structure constructed from [Cr(OH)6Mo6O18]3-
      building blocks and Ag-pyridine-4-carboxylic acid coordination units. The crystal
      data for these compounds are the following: 1, triclinic, P1, a = 13.280(3) A, b
      = 13.641(3) A, c = 16.356(3) A, alpha = 89.68(3) degrees, beta = 88.31(3)
      degrees, gamma = 75.87(3) degrees, Z = 2; 2, triclinic, P1, a = 11.978(2) A, b =
      12.008(2) A, c = 13.607(3) A, alpha = 116.14(3) degrees, beta = 108.85(3)
      degrees, gamma = 93.86(3) degrees, Z = 1; 3, triclinic, P1, a = 10.458(2) A, b =
      10.644(2) A, c = 12.295(3) A, alpha = 97.40(3) degrees, beta = 112.38(3) degrees,
      gamma = 113.59(3) degrees, Z = 1.

PMID- 16097827
TI  - Charge transport and optical properties of MOCVD-derived highly transparent and
      conductive Mg- and Sn-doped In2O3 thin films.
AB  - Mg- and Sn-doped In2O3 (MgIn(x)Sn(y)O(z), 6.0 < x < 16.0; 3.0 < y < 8.0) thin
      films were grown by low-pressure metal-organic chemical vapor deposition using
      the volatile metal-organic precursors tris(2,2,6,6-tetramethyl-3,5
      heptanedionato)indium(III) [In(dpm)3], bis(2,4-pentanedionato)tin(II)
      [Sn(acac)2], and bis(2,2,6,6-tetramethyl-3,5-heptanedionato)(N,N,N',N'
      tetramethylethylenediamine)magnesium(II) [Mg(dpm)2(TMEDA)]. Films in this
      compositional range retain the cubic In2O3 bixbyite crystal structure. The
      highest conductivity is found to be approximately 1000 S/cm for an as-grown film
      with a nominal composition MgIn14.3Sn6.93O(z). Annealing of such films in a
      vacuum raises the conductivity to approximately 2000 S/cm. The optical
      transmission window of the present films is significantly wider than that of
      typical indium tin oxide (ITO) films from 300 to 3300 nm, and the transmittance
      is also greater than or comparable to that of commercial ITO films.

PMID- 16097828
TI  - Disulfide bond cleavage induced by a platinum(II) methionine complex.
AB  - The cleavage of a disulfide bond and the redox equilibrium of thiol/disulfide are
      strongly related to the levels of glutathione (GSH)/oxidized glutathione (GSSG)
      or mixed disulfides in vivo. In this work, the cleavage of a disulfide bond in
      GSSG induced by a platinum(II) complex [Pt(Met)Cl2] (where Met = methionine) was
      studied and the cleavage fragments or their platinated adducts were identified by
      means of electrospray mass spectrometry, high-performance liquid chromatography,
      and ultraviolet techniques. The second-order rate constant for the reaction
      between [Pt(Met)Cl2] and GSSG was determined to be 0.4 M(-1) s(-1) at 310 K and
      pH 7.4, which is 100- and 12-fold faster than those of cisplatin and its monoaqua
      species, respectively. Different complexes were formed in the reaction of
      [Pt(Met)Cl2] with GSSG, mainly mono- and dinuclear platinum complexes with the
      cleavage fragments of GSSG. This study demonstrated that [Pt(Met)Cl2] can promote
      the cleavage of disulfide bonds. The mechanistic insight obtained from this study
      may provide a deeper understanding on the potential involvement of platinum
      complexes in the intracellular GSH/GSSG systems.

PMID- 16097829
TI  - Comparative studies of substitution reactions of rhenium(I) dicarbonyl-nitrosyl
      and tricarbonyl complexes in aqueous media.
AB  - The ligand substitution behavior of [ReBr3(CO)3](NEt4)2 (1) and
      [ReBr3(CO)2(NO)]NEt4 (2) in aqueous media was compared. Ligand exchange reactions
      were performed with multidentate chelating systems such as picolylaminediacetic
      acid (L1; N,N',O,O'), nitrilotriacetic acid (L2; N,O,O',O''), iminodiacetic acid
      (L3; N,O,O'), and bis(2-pyridyl)methane (L4; N,N'). The products of the
      substitution reactions were isolated and characterized by means of IR, NMR, MS,
      and X-ray structure analysis. NMR and crystallographic analyses confirmed the
      formation of single structural isomers in all cases with a ligand-to-metal ratio
      of 1:1. With ligands L1 and L2 and precursor 1 the tridentately coordinated
      complexes [Re(L1)(CO)3] (7) and [Re(L2)(CO)3]2- (8) were formed. With precursor 2
      the same ligands unexpectedly coordinated tetradentately after displacing a CO
      ligand, yielding complexes [Re(L1)(CO)(NO)] (3) and [Re(L2)(CO)(NO)]- (4). In
      both complexes NO was found to be coordinated trans to the carboxylate group.
      Time-dependent IR spectra of the reaction of 2 with ligand L1 and L2 confirmed
      the loss of one CO during the reaction. The product of the reaction of 2 with L3
      was identified as the neutral complex [Re(L3)(CO)2(NO)] (5), again, with the
      nitrosyl coordinated trans to the carboxylate. With 1, ligand L3 formed the
      anionic complex [Re(L3)(CO)3]- (9). Finally the reactions with L4 yielded the
      complexes [ReBr(L4)(CO)2(NO)]Br (6) and [ReBr(L4)(CO)3] (10), in which bromide
      was found to be coordinated trans to the NO and CO, respectively. The X-ray
      structures of 3, 5-7, and 10 are discussed: 3, monoclinic P2(1)/n, with a =
      14.6071(6) A, b = 8.0573(3) A, c = 24.7210(11) A, beta = 107.117(5) degrees, and
      Z = 4; 5, triclinic P1, with a = 6.9091(5) A, b = 9.8828(7) A, c = 14.2834(10) A,
      alpha = 89.246(9) degrees, beta = 89.420(9) degrees, gamma = 86.196(9) degrees,
      and Z = 4; 6, triclinic P1, with a = 9.8236(8) A, b = 10.0949(8) A, c =
      12.5346(10) A, alpha = 108.679(9) degrees, beta = 111.992(9) degrees, gamma =
      95.426(10) degrees, and Z = 2; 10, monoclinic P2(1)/c, with a = 12.7491(12) A, b
      = 13.3015(13) A, c = 9.0112(9) A, beta = 107.195(2) degrees, and Z = 7.

PMID- 16097830
TI  - Complex series [Ru(tpy)(dpk)(X)]n+ (tpy = 2,2':6',2''-terpyridine; dpk = 2,2'
      dipyridyl ketone; X = Cl-, CH3CN, NO2(-), NO+, NO*, NO-): substitution and
      electron transfer, structure, and spectroscopy.
AB  - The complex framework [Ru(tpy)(dpk)]2+ has been used to study the generation and
      reactivity of the nitrosyl complex [Ru(tpy)(dpk)(NO)]3+ ([4]3+). Stepwise
      conversion of the chloro complex [Ru(tpy)(dpk)(Cl)]+ ([1]+) via
      [Ru(tpy)(dpk)(CH3CN)]2+ ([2]2+) and the nitro compound [Ru(tpy)(dpk)(NO2)]+
      ([3]+) yielded [4]3+; all four complexes were structurally characterized as
      perchlorates. Electrochemical oxidation and reduction was investigated as a
      function of the monodentate ligand as was the IR and UV-vis spectroscopic
      response (absorption/emission). The kinetics of the conversion [4]3+/[3]+ in
      aqueous environment were also studied. Two-step reduction of [4]3+ was monitored
      via EPR, UV-vis, and IR (nu(NO), nu(CO)) spectroelectrochemistry to confirm the
      {RuNO}7 configuration of [4]2+ and to exhibit a relatively intense band at 505 nm
      for [4]+, attributed to a ligand-to-ligand transition originating from bound NO-.

PMID- 16097831
TI  - Synthesis, characterization, crystal structure, and electrochemical,
      photophysical, and protein-binding properties of luminescent rhenium(I) diimine
      indole complexes.
AB  - We report the synthesis, characterization, and photophysical and electrochemical
      properties of a series of luminescent rhenium(I) diimine indole complexes, [Re(N
      N)(CO)3(L)](CF3SO3) (N-N = 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4-phen), L
      = N-(3-pyridoyl)tryptamine (py-3-CONHC2H4-indole) (1a), N-[N-(3-pyridoyl)-6
      aminohexanoyl]tryptamine, (py-3-CONHC5H10CONHC2H4-indole) (1b); N-N = 1,10
      phenanthroline (phen), L = py-3-CONHC2H4-indole (2a), py-3-CONHC5H10CONHC2H4
      indole (2b); N-N = 2,9-dimethyl-1,10-phenanthroline (Me2-phen), L = py-3-CONHC2H4
      indole (3a), py-3-CONHC5H10CONHC2H4-indole (3b); N-N = 4,7-diphenyl-1,10
      phenanthroline (Ph2-phen), L = py-3-CONHC2H4-indole (4a), py-3-CONHC5H10CONHC2H4
      indole (4b)), and their indole-free counterparts, [Re(N-N)(CO)3(py-3-CONH
      Et)](CF3SO3) (py-3-CONH-Et = N-ethyl-(3-pyridyl)formamide; N-N = Me4-phen (1c),
      phen (2c), Me2-phen (3c), Ph2-phen (4c)). The X-ray crystal structure of complex
      3a has also been investigated. Upon irradiation, most of the complexes exhibited
      triplet metal-to-ligand charge-transfer (3MLCT) (d pi(Re) --> pi*(diimine))
      emission in fluid solutions at 298 K and in low-temperature glass. However, the
      structural features and long emission lifetimes of the Me4-phen complexes in
      solutions at room temperature suggest that the excited state of these complexes
      exhibited substantial triplet intraligand (3IL) (pi --> pi*) (Me4-phen)
      character. The binding interactions of these complexes to indole-binding proteins
      including bovine serum albumin and tryptophanase have been examined.

PMID- 16097832
TI  - Reactions of 2-(arylazo) aniline with RhCl3: synthesis and structure of new
      cyclometalated complexes of Rh(III) and recognition of RhCl3 assisted azo (-N=N-)
      cleavage.
AB  - The reactions of 2-(arylazo) anilines, HL (1) [where HL is 2-(ArN=N)C6H4NH2; Ar
      is C6H5 (for HL1, 1a) and p-MeC6H4 (for HL2, 1b); H of HL represents the proton
      of Ar which gets dissociated upon orthometalation] with RhCl3 in methanol
      afforded new orthometalated complexes of composition (L)(HL)Rh(III)Cl2 (2) and
      (L)(ArNH2)Rh(III)Cl2 (3). The anionic L- binds the metal in tridentate (C, N, N)
      manner in both the complexes, while HL and ArNH2 bind the metal of 2 and 3 in
      monodentate fashion through the amino nitrogen. The ArNH2 of 3 was formed in situ
      due to cleavage of azo (-N=N-) function of monodentate HL of 2. The scission of
      N=N has been authenticated.

PMID- 16097833
TI  - Practical synthetic routes to solvates of U(OTf)3: X-ray crystal structure of
      [U(OTf)3(MeCN)3]n, a unique U(III) coordination polymer.
AB  - The reaction of UH3 or U metal with triflic acid results in the formation of a
      mixture of species including U(OTf)4 and leads to the reproducible isolation of
      the mononuclear U(IV) hydroxo complex [U(OTf)3(OH)(py)4] (1) and the U(IV)
      dinuclear mu-oxo-complex [{U(OTf)2(py)3}2{mu-O}{mu-OTf}2] (2). The X-ray crystal
      structures of these complexes have been determined. Analytically pure complex 1
      can be prepared in a 17-27% yield providing a good precursor for the synthesis
      and study of the reactivity of the hydroxo complexes with different coordination
      environments. Two practical synthetic methods for the preparation of Lewis base
      adducts of U(OTf)3 are described. Analytically pure [U(OTf)3(py)4] (4) was easily
      and reproducibly prepared (50-60% yield) by protonolysis of the amide
      U{N(SiMe3)2}3 with pyridinium triflate in pyridine. Salt metathesis of UI3(thf)4
      with potassium triflate in acetonitrile resulted in the complete substitution of
      the iodide counterions by triflate producing the acetonitrile solvate
      [U(OTf)3(MeCN)3]n (3). The solid-state structure of 3 shows the formation of a
      unique U(III) coordination polymer in which the metal ions are connected by three
      triflates acting as bidentate bridging ligands to form a 1D chain.

PMID- 16097834
TI  - Mononuclear and dinuclear copper(I) complexes of bis(3,5-dimethylpyrazol-1
      yl)methane: synthesis, structure, and reactivity.
AB  - The synthesis and structures of a mononuclear copper(I) carbonyl complex
      [Cu(OClO3)(CO)(H2CPz2')] (3) and a dinuclear copper(I) carbonyl complex
      [{Cu(CO)(H2CPz2')}2(mu-pyrazine)](ClO4)2 (4), where H2CPz2' = bis(3,5
      dimethylpyrazol-1-yl)methane, are described. These two compounds were generated
      by the carbonylation of the corresponding copper(I)-acetonitrile complexes,
      [Cu(H2CPz2')(MeCN)](ClO4) (1) and [{Cu(H2CPz2')(MeCN)}2(mu-pyrazine)](ClO4)2 (2).
      Alternatively, treatment of mononuclear 1 and 3, respectively, with pyrazine in a
      molar ratio of 2:1 produces the pyrazine-bridged dinuclear Cu(I) complexes 2 and
      4. Each of the complexes 1-4 can react with PPh3 to generate a common three
      coordinated copper(I) complex [Cu(PPh3)(H2CPz2')](ClO4) (5). The structures of
      complexes 1-5 were all confirmed by X-ray crystallography. Comparison of the
      Cu(I)-C(CO) bond distances and the CO stretching frequencies of 3 and 4 indicates
      the back-donating properties of d pi(Cu)-pi*(pyrazine) bonds in 4, and
      accordingly, stabilizes the mixed-valence species generated from 2. Complex 3,
      stabilized by the strong interaction between copper(I) ion and perchlorate
      counteranion (Cu(I)-O(ClO4) = 2.240(3) A), is a potential precursor for
      polynuclear copper(I) carbonyl complexes.

PMID- 16097835
TI  - Searching for precursors to metal-metal bonded dipalladium species: a study of
      Pd2(4+) complexes.
AB  - Reactions of Pd3(OAc)6 with lithium salts of mononegative bidentate N,N-ligands,
      L, of various types, such as formamidinates, benzamidinates, triazinates, and
      guanidinates, were investigated in a search for ways to obtain Pd2(4+) compounds
      that could serve as precursors to paddlewheel complexes with a metal-metal bond
      and a Pd2(5+) core. It was found that the reactions are complex and that either
      square planar mononuclear or dinuclear species may be formed depending on the
      reaction conditions or the method of isolation. For Pd2L4 compounds, alpha and
      beta isomers were sometimes obtainable. In the alpha isomer, all N,N-ligands
      serve as bridges, whereas in the beta isomer, two ligands bridge the Pd2(4+) unit
      and each of the other two chelate to a metal atom. Electrochemistry shows that
      the paddlewheel compounds Pd2(TolNC(H)NTol)4, Pd2(PhNC(Ph)NPh)4, and
      Pd2(PhNC(Ph)NPh)3(OAc) and the orthometalated complex cis-Pd2[eta2
      C6H4NC(Ph)N(H)Ph]2(mu-OAc)2 have reversible oxidation waves between 0.70 and 0.92
      V vs Ag/AgCl, which makes them good candidates for chemical oxidation.

PMID- 16097837
TI  - Real-world trials to answer real-world questions.
AB  - Currently, there is a discrepancy between clinical trials designed to assess the
      efficacy and safety of a new medication under investigation and the real-life
      questions that need to be addressed regarding the clinical use of the medication
      by patients, healthcare professionals and society. The data necessary to obtain
      regulatory approval may be of limited relevance to policy makers when calculating
      economic parameters such as value for money or cost effectiveness. 'Real-world'
      studies examine questions relevant to health policy and reimbursement. There are
      many different forms of clinical trials, but in designing trials incorporating
      realistic budget impact estimates the important issue is to ensure we are asking
      a sensible question and attempting to answer it with an appropriate experimental
      design. As an example, a real-world trial currently underway that examines
      scenarios of introducing inhaled insulin into clinical practice is described.

PMID- 16097838
TI  - Pharmaceutical policy regarding generic drugs in Belgium.
AB  - Pressure to control pharmaceutical expenditure and price competition among
      pharmaceutical companies are fuelling the development of generic drug markets in
      EU countries. However, in Belgium, the market for generic drugs is underdeveloped
      compared with other countries. To promote the use of generic drugs, the
      government introduced a reference pricing (RP) scheme in 2001. The aim of this
      paper is to discuss Belgian pharmaceutical policy regarding generic drugs and to
      analyse how the Belgian drug market has evolved following initiation of the RP
      scheme. The market share held by generic drugs increased following implementation
      of the RP scheme. Focusing on volume, average market share (by semester) for
      generic drugs amounted to 2.05% of the total pharmaceutical market from January
      1998 to June 2001, compared with 6.11% from July 2001 to December 2003. As new
      generic drugs are introduced, their market share tends to increase in the first
      couple of months, after which it levels off. Faced with increasing generic
      competition, some manufacturers have launched new variants of their original
      drug, thereby effectively extending the period of patent protection. Strategies
      consisting of price reductions in return for the abolition of prescribing
      conditions and the launch of new dosages or formulations appear to have been
      successful in maintaining the market share of original drugs. Nevertheless, the
      introduction of the RP scheme was associated with savings amounting to 1.8% of
      pharmaceutical expenditure by the third-party payer in 2001 and 2.1% in 2002. The
      findings of this paper indicate that the RP scheme has stimulated the Belgian
      generic drug market. However, existing policy has largely failed to take into
      account the role that physicians and pharmacists can play in stimulating generic
      drug use. Therefore, further development of the Belgian generic drug market seems
      to hinge on the creation of appropriate incentives for physicians to prescribe,
      and for pharmacists to dispense, generic drugs. With respect to incentives to
      advance generic drug use, EU countries have experimented with various forms of
      budget constraints for physicians, generic substitution by pharmacists and RP
      schemes, although more evidence is needed of their impact on consumption and
      prices of generic drugs, pharmaceutical expenditure and health outcomes.

PMID- 16097839
TI  - Granulocyte colony--stimulating factor for chemotherapy-induced neutropenia in
      patients with small cell lung cancer : the 40% rule revisited.
AB  - Recombinant granulocyte colony-stimulating factor (G-CSF) [filgrastim and
      lenograstim] and pegylated G-CSF (pegfilgrastim) have been shown to reduce the
      severity and duration of chemotherapy-associated febrile neutropenia (FN) when
      administered prophylactically to cancer patients receiving chemotherapeutic
      regimens. The American Society of Clinical Oncology (ASCO) evidence-based
      clinical guidelines published in 1994, 1996 and 1997 recommended primary
      prophylaxis with G-CSF for cancer patients. The 2000 ASCO update, with the same
      recommendation, highlights the importance of economic considerations in decision
      making for CSFs. This paper reviews the available cost-effectiveness evidence on
      the use of G-CSF as primary prophylaxis against FN in patients with small cell
      lung cancer (SCLC).Cost-effectiveness ratios from a healthcare payer perspective
      supported the use of filgrastim as primary prophylaxis for people with SCLC, on
      the basis of both clinical and economic benefits, treated with chemotherapeutic
      regimens that have an FN rate in the range of 40-60%. However, when indirect and
      patient out-of-pocket costs attributable to severe FN are included, available
      evidence suggests that the risk threshold may be reduced by more than half. Given
      that FN rates associated with chemotherapeutic regimens for SCLC are generally
      <40%, then few circumstances would warrant the use of G-CSFs (filgrastim and
      lenograstim) under the current rule. However, inclusion of indirect costs would
      lower the cost-effectiveness threshold. Future cost-effectiveness studies of
      medications such as pegfilgrastim should attempt to capture the societal
      perspective by incorporating productivity-related costs and using base-case rates
      of FN reported in the literature.

PMID- 16097840
TI  - Parent-proxy EQ-5D ratings of children with attention-deficit hyperactivity
      disorder in the US and the UK.
AB  - BACKGROUND: The symptoms of attention-deficit hyperactivity disorder (ADHD) are
      associated with impairment in multiple domains of health-related quality of life
      (HR-QOL). HR-QOL of children with ADHD has been assessed by relatively long
      multidimensional questionnaires. A review of the literature found no studies
      using the brief, well established EuroQoL Five-Dimension Questionnaire (EQ-5D) to
      estimate the HR-QOL of children with ADHD. The objective of this study was to
      assess the HR-QOL of children with ADHD using parents' responses to the proxy
      version of the EQ-5D. METHODS: Participants were recruited in the midwestern US
      and in the vicinity of London, England. All parents completed three
      questionnaires: the EQ-5D proxy version; a measure of ADHD symptoms based on
      Diagnostic and Statistical Manual of Mental Disorders (4th Edition) [DSM-IV]
      criteria (the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV - Parent
      Version [ADHD-RS]); and either the Child Health Questionnaire - Parent Form 50
      (CHQ-PF50) or the Child Health and Illness Profile - Child Edition (CHIP-CE),
      which are both generic multidimensional paediatric HR-QOL questionnaires.
      RESULTS: A total of 126 parents of children with ADHD participated in the study:
      43 in the US and 83 in the UK. On the EQ-5D, participants indicated that 78.6% of
      their children experienced some problems or extreme problems performing usual
      activities, while 64.8% believed their child demonstrated some or extreme anxiety
      or depression. The mean EQ-5D index score was 0.75 and the mean visual analogue
      scale (VAS) score was 73.9. The EQ-5D index and VAS scores were found to be
      significantly correlated (p < 0.05) with several domains of the CHQ-PF50 (e.g.
      Mental Health, Self-Esteem, Family Activities, Psychosocial Summary Score) and
      the CHIP-CE (e.g. Satisfaction, Comfort, Academic Performance, Peer Relations).
      The EQ-5D scales were also significantly correlated with the ADHD-RS scales (p <
      0.001). CONCLUSION: The proxy version of the EQ-5D, completed by parents, was
      able to detect impairment in children diagnosed with ADHD in the US and the UK.
      Furthermore, the EQ-5D index and VAS scores demonstrated construct validity among
      this sample through significant correlations with an ADHD symptom measure and
      previously validated multidimensional QOL instruments. These results suggest that
      parent-proxy EQ-5D ratings are feasible and valid for use as part of an overall
      health outcomes assessment in clinical studies of childhood ADHD.

PMID- 16097841
TI  - Societal discounting of health effects in cost-effectiveness analyses: the
      influence of life expectancy.
AB  - BACKGROUND: Increasing life expectancy and decreasing marginal valuation of
      additional QALYs over time may serve as a basis for discounting future health
      effects from a societal perspective. Therefore, we tested the hypothesis that
      societal time preference for health is related to perceived future life
      expectancy. METHODS: A sample of 223 people from the general population
      prioritised healthcare programmes with differential timing of health benefits and
      costs from a societal perspective. Furthermore, we asked respondents to estimate
      future life expectancy. RESULTS: The relationship between future life expectancy
      and time preference for health is ambiguous. We observed that people who expected
      a higher future life expectancy elicited higher discount rates for health effects
      than those with lower life expectancy growth expectations for all four time
      periods (5, 10, 20 and 40 years into the future), but the differences were never
      significant. On average, providing explicit information on growth in life
      expectancy did significantly alter discount rates in the expected direction but,
      on an individual level, the results were rather inconsistent. We observed a
      significantly stronger time preference (i.e. higher discount rates) for health
      effects than for costs. As commonly observed, discount rates for health and money
      decreased with time delay following a hyperbolic function. CONCLUSION: Our data
      indicate that it is troublesome to elicit societal discount rates empirically,
      especially rates that are in line with the theoretical arguments on societal
      discounting. The influence of life expectancy remains ambiguous, but there seems
      to be at least some positive relationship between growth in life expectancy and
      discount rates that deserves additional attention.

PMID- 16097842
TI  - Economic evaluation of temozolomide in the treatment of recurrent glioblastoma
      multiforme.
AB  - BACKGROUND: Temozolomide (TMZ) is an oral alkylating agent with demonstrated
      efficacy as therapy for glioblastoma multiforme (GBM) and anaplastic astrocytoma.
      TMZ has widely replaced the procarbazine, lomustine plus vincristine (PCV)
      combination for the treatment of malignant brain tumours as a result of its oral
      administration and favourable toxicity profile. OBJECTIVES: This study had three
      related aims. First, the cost effectiveness of TMZ (from the Finnish healthcare
      payer perspective) was compared with PCV in patients with GBM that had relapsed
      after primary treatment with surgery and radiotherapy. Second, the probability
      that TMZ is cost effective, compared with PCV, was estimated at different
      societal willingness-to-pay levels. Third, the value of new information for
      reducing the uncertainty related to the choice of treatment between TMZ and PCV
      was evaluated. METHODS: The cost effectiveness of TMZ and PCV was evaluated using
      a decision-modelling approach. Incremental cost-effectiveness ratios (ICERs) for
      cost per gained life-month, progression-free life-month and QALY were calculated.
      Various information sources were used to acquire parameter values for the model.
      The efficacy information of both treatments was derived from the medical
      literature, quality-of-life (QOL) estimates were gathered from Finnish neuro
      oncologists using visual analogue scale methods, and data on the use of
      healthcare resources were collected from hospital databases. The exact prices for
      resource use were gained from the list of Finnish health service unit costs (year
      2001 prices). The model was analysed using second-order Monte Carlo simulation.
      The value of new information on reducing uncertainty was analysed using the
      expected value of perfect information (EVPI) approach. RESULTS: According to the
      derived ICERs, 1 extra life-month gained with TMZ costs euro2367, 1 extra
      progression-free life-month costs euro2165, and 1 extra QALY costs euro32 471,
      compared with PCV, in the treatment of GBM. The probability of TMZ being the most
      cost-effective choice of treatment was >60% for all levels of willingness to pay
      >euro5000 per gained life-month. The respective probabilities were >75% for all
      levels of willingness to pay >euro10 000 per gained progression-free life-month
      and about 85% for all levels of willingness to pay >euro20 000 per gained quality
      adjusted life-month. According to EVPI analysis, future research would
      potentially be cost effective if the costs of research were euro4.1 million
      (maximum). CONCLUSIONS: On the basis of this Finnish analysis, TMZ has a high
      probability of being more cost effective than PCV for patients with GBM. The
      addition of QOL aspects to the prolonging of survival increases the probability
      further.

PMID- 16097843
TI  - Cost of illness and its predictors for Parkinson's disease in Germany.
AB  - OBJECTIVE: To prospectively evaluate the health economic burden of patients with
      Parkinson's disease (PD) in Germany over a 6-month observation period and to
      identify the predictors of these costs. STUDY DESIGN AND METHODS: Direct and
      indirect costs were evaluated in 145 patients with PD (mean age 67.3 +/- 9.6
      years). PD patients were recruited from an outpatient department for movement
      disorders, a specialised PD clinic, two office-based neurologists and general
      practitioners, all located in Germany, and were enrolled between January and June
      2000. Relevant economic data were documented in a patient diary over the 6-month
      period. Clinical evaluations (Unified Parkinson's Disease Rating Scale [UPDRS])
      were performed at baseline and at 3 and 6 months. Costs were derived from various
      German medical economic resources. Costs were calculated from the perspective of
      healthcare and transfer payment providers and the individual patient. Indirect
      costs for lost productivity were also calculated. Costs are presented as means +/
      standard deviation (SD). Multivariate regression analyses were performed to
      identify independent cost predictors. Costs are in year 2000-02 values. RESULTS:
      We estimated average per patient direct, indirect and total costs for the 6-month
      observation period. The costs from the perspective of statutory health insurance
      (Gesetzliche Krankenkversicherung [GKV]) consisted of direct medical costs 1370
      euro +/- 3240 euro, including rehabilitation (420 euro +/- 1630 euro),
      hospitalisation (710 euro +/-2520 euro), outpatient treatment (40 euro +/- 30
      euro), ancillary treatment (190 euro +/- 280 euro) and ambulatory diagnostic
      procedures (10 euro +/-30 euro). In addition, parkinsonian drug costs were 1520
      euro +/-euro1250. Non-medical direct costs calculated from the GKV perspective
      were estimated to be euro480 +/-euro1710, which included transportation (10
      euro+/- 20 euro), special equipment (420 euro +/- 1640 euro), social/home-help
      services (10 euro +/-110 euro) and sickness benefit (40 euro +/- 540 euro). The
      total medical (including drug costs) and non-medical direct costs for the GKV
      were 3380 euro +/- 4230 euro. Univariate predictors for GKV direct costs included
      occurrence of motor complications and falls, disease severity, nightmares and
      dementia. However, multivariate analyses only suggested disease severity and
      health-related quality of life as significant predictors. For nursing insurance,
      payments of 1330 euro +/- 2890 euro were calculated. For retirement insurance,
      payments were 650 euro +/- 1510 euro and there were patient (or caregiver) costs
      of 1490 euro +/- 2730 euro. Total indirect costs amounted to 3180 euro +/-6480
      euro. CONCLUSION: According to our study, PD puts a high financial burden on
      society and underscores the need for further economic and medical research to
      optimise treatment for PD.

PMID- 16097844
TI  - An economic evaluation of rizatriptan in the treatment of migraine.
AB  - BACKGROUND: Migraine is a common, chronic, neurovascular disorder, generally
      characterised by attacks of severe headache and autonomic nervous system
      dysfunction. Triptans are selective serotonin 5-HT(1B/1D) receptor agonists that
      represent effective therapeutic options for moderate-to-severe migraine attacks
      but with higher acquisition costs relative to usual care therapies. OBJECTIVE:
      The objective of this study was to examine the cost effectiveness of rizatriptan
      treatment compared with 'Usual Care' or other triptans available in Canada for
      patients with moderate-to-severe migraine for whom other therapies (e.g. NSAIDs,
      simple analgesics) are insufficient or contraindicated. METHODS: A decision
      analysis model was created to estimate migraine treatment costs over a 24-hour
      period in patients with a diagnosis of moderate-to-severe migraine as defined by
      the International Headache Society criteria. Costs and clinical outcomes were
      observed over a 24-hour period from therapy initiation. Efficacy measures
      consisted of 'pain-free response at 2 hours' and 'sustained pain free for 2-24
      hours'. Oral rizatriptan 10 mg was compared with other oral triptans (i.e.
      sumatriptan 50 or 100 mg), naratriptan 2.5 mg and zolmitriptan 2.5 mg, based on a
      meta-analysis and compared with 'Usual Care' based on a naturalistic study of
      people who experience migraine and who were similar to the target population.
      'Usual Care' was defined as an aggregate of medications prescribed for the
      Canadian population for the indication of migraine, weighted by the relative
      frequency of use of prescriptions over a 1-year period. Analyses were conducted
      from the Ontario (Canada) Ministry of Health and Long-Term Care (MOH<C)
      perspective and the broader societal perspective. Results are presented as the
      cost per migraine attack aborted (i.e. pain free at 2 hours), as well as the cost
      per QALY. Several one-way sensitivity analyses were conducted to test the
      robustness of the model. All costs are expressed in 2002 $Can. RESULTS: Cost
      estimates are similar to previously published Canadian studies. Rizatriptan
      compared with 'Usual Care' produced an incremental cost per attack aborted of
      $Can49.82 and a cost per QALY gained of $Can31 845 from the MOH<C perspective.
      When a societal perspective was considered (which included time loss from paid
      and unpaid work activities), rizatriptan dominates 'Usual Care': that is, it is
      cost saving and more effective. All other triptans are also dominated by
      rizatriptan as they offer higher costs and lower efficacy. CONCLUSIONS: This
      study shows that rizatriptan treatment for patients who experience moderate-to
      severe migraines may represent a cost-effective strategy for improving care of
      migraine patients in Canada.

PMID- 16097845
TI  - Incorporation of uncertainty in health economic modelling studies.

PMID- 16097847
TI  - Substance abuse in patients with attention-deficit hyperactivity disorder :
      therapeutic implications.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common disorder in children
      that frequently persists into adulthood. Studies have found that substance use
      disorders (SUD) are seen more commonly in those with ADHD than the general
      population. Although treatment with stimulant medications has been shown to be
      effective for individuals with ADHD, concern about the use of these agents in
      this population persists. This review article highlights the research in this
      area with a focus on the treatment of individuals who present with concomitant
      ADHD and SUD. Although stimulants can be abused, studies have shown that
      adolescents who are prescribed stimulants for ADHD have lower rates of SUD than
      those who are not treated with stimulants. It may be particularly difficult to
      evaluate adults for the diagnosis of ADHD when SUD is a co-morbid factor. Studies
      show that 20--30% of adults presenting with SUD have concomitant ADHD and
      approximately 20--40% of adults with ADHD have histories of SUD. Therefore, it is
      critical to perform careful diagnostic interviews to discern if patients have
      either or both of these disorders. Many clinical experts suggest that adults with
      ADHD and active SUD be treated for the SUD until a period of sobriety persists
      prior to initiation of specific treatment for ADHD. Since individuals with ADHD
      and active SUD are more likely to have more severe SUD and a worse prognosis,
      this approach may not serve many patients, as they relapse prior to obtaining
      ADHD treatment. Therefore, research has been directed towards determining if the
      treatment of ADHD with stimulant medications can be safe and effective for the
      individual with active SUD and concomitant ADHD. An initial trial of
      methylphenidate in a population of adults with active cocaine dependence and ADHD
      indicates that this is the case. Individuals with ADHD and SUD can present
      difficult diagnostic and therapeutic challenges. It appears that the most
      effective treatment option is to create a programme that uses the most effective
      treatment modalities available, including both behavioural and medical therapies,
      along with close supervision and monitoring. Newer medical treatment options of
      long-acting stimulants and non-stimulants (e.g. atomoxetine) offer effective
      treatment with a lower risk of abuse potential.

PMID- 16097848
TI  - Erotomania : epidemiology and management.
AB  - Erotomania is generally classified as a delusional disorder in contemporary
      classification systems (DSM-IV and ICD-10). The incidence of erotomania is not
      known, but that of delusional disorder in general has been reported as
      approximately 15 cases per 100,000 of the population per year, with a female :
      male ratio of 3 : 1. Both primary and secondary types of erotomania have been
      identified, the latter being associated with evidence of an aetiologically
      significant organic or psychiatric condition. The aetiology of primary erotomania
      is not yet fully understood, but neuroimaging, genetic studies and findings from
      evolutionary psychopathology hold considerable promise for a deeper and broader
      understanding of this condition. The initial management of secondary erotomania
      focuses on treating the underlying organic or psychiatric illness. The management
      of primary and secondary erotomania involves a combination of pharmacological
      treatments, psychosocial interventions and risk management strategies. In the
      past, the antipsychotic medication pimozide was commonly used, at least in
      certain countries (such as the US and Canada), despite a paucity of systematic
      studies of its use in this disorder. In recent years, there have been reports of
      positive therapeutic outcomes with atypical antipsychotics (risperidone,
      clozapine), which, as a result of their improved tolerability over older agents
      such as pimozide, will hopefully enhance patient acceptability and, thereby,
      improve clinical outcome. Despite this advance, there is still a strong need for
      controlled clinical trials of therapeutic strategies for primary erotomania and
      related syndromes.

PMID- 16097849
TI  - AIDS-associated progressive multifocal leukoencephalopathy : current management
      strategies.
AB  - Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic
      infection of the CNS by the ubiquitous JC virus (JCV). PML is only seen in the
      context of severe and prolonged immunosuppression, a phenomenon now frequently
      encountered since the AIDS pandemic. PML is characterised by progressive lysis of
      oligodendrocytes with demyelination. A rapid clinical course ensues with focal
      neurological deficits and a median time to death of 3.5 months without treatment.
      Prior to highly active antiretroviral therapy (HAART), there was no effective
      therapy. Since the advent of HAART, the prognosis for PML has much improved;
      however, a significant number of patients appear unresponsive to antiretrovirals
      and some worsen because of the development of immune reconstitution disease. A
      better understanding of the biology of JCV and its interactions with host cells
      is leading to new anti-JCV-specific agents that await evaluation in randomised,
      controlled trials. Improved diagnostic tools and the possibility of immunotherapy
      and gene therapy are further advancing the field.

PMID- 16097850
TI  - The risk of stroke in patients with migraine and implications for migraine
      management.
AB  - Assessing the risk of stroke in persons with migraine is complicated by the
      intricate relationship between these two conditions. Both migraine and stroke are
      common and co-morbidity may, in some cases, be coincidental. Given the overlap of
      clinical symptoms in stroke and migraine, each condition may also mimic the
      other. Numerous studies have, however, shown that migraine is an independent risk
      factor for stroke both during, and remote from, the migraine attack. Women of
      childbearing age and those with aura are at greatest risk of migraine-related
      stroke. Additional risk of stroke in migraineurs occurs in those using oral
      contraceptive pills and who smoke cigarettes. Elevated blood pressure, an
      important stroke risk factor, is less common in migraineurs. Acquired
      antiphospholipid antibodies, not clearly a cause of migraine per se, may raise
      the risk of infarction in migraineurs. Hereditary conditions, including CADASIL
      (cerebral autosomal dominant arteriopathy with sub-cortical infarcts and
      leukoencephalopathy), MELAS (mitochondrial myopathy, encephalopathy, lactacidosis
      and stroke) and hereditary haemorrhagic telangiectasia, appear to predispose to
      both migraine and stroke. Purported mechanisms for migraine-associated stroke
      include involvement of the vasculature (including vasospasm, arterial dissection
      and small vessel arteriopathy), hypercoagulability (elevated von Willebrand
      Factor, platelet activation) and elevated risk of cardioembolism (patent foramen
      ovale, atrial septal aneurysm). Triptans and ergotamines, used to treat acute
      migraine attacks, appear to be safe in low-risk populations. These medications
      should be avoided in persons with haemiplegic migraine, basilar migraine,
      vascular risk factor and prior cerebral or cardiac ischaemia.

PMID- 16097852
TI  - Extended-release carbamazepine capsules : in bipolar I disorder.
AB  - An extended-release capsule formulation of carbamazepine is approved for use in
      adult patients experiencing an acute manic or mixed episode associated with
      bipolar I disorder. A capsule of extended-release carbamazepine contains three
      types of bead: immediate release, extended release and enteric release,
      constituting 25%, 40% and 35% of the dose, respectively.black triangle Extended
      release carbamazepine capsules 200--1600 mg/day demonstrated superior antimanic
      efficacy to placebo in two 3-week, well designed trials in adult patients with
      bipolar I disorder and acute manic or mixed episodes. At study end, reductions
      from baseline in Young Mania Rating Scale scores were significantly greater with
      carbamazepine than with placebo (primary endpoint). The active treatment was
      effective from the end of the first week of treatment (post hoc analysis).black
      triangle In the 3-week trials and a 6-month extension study, most treatment
      emergent adverse events observed with extended-release carbamazepine were of mild
      or moderate severity. In the 3-week trials, although significantly greater
      reductions in white blood cell count occurred with extended-release carbamazepine
      than with placebo, only one case of leukopenia was deemed serious. There were no
      reports of agranulocytosis or aplastic anaemia with up to 6 months' treatment.

PMID- 16097853
TI  - Extended-release carbamazepine capsules: a viewpoint.

PMID- 16097851
TI  - The opioidergic-alcohol link : implications for treatment.
AB  - Preclinical and clinical data implicate the endogenous opioid system in alcohol
      dependence. In vitro studies show that rodent pituitary and hypothalamic tissue
      responds to acute exposure to alcohol by releasing beta-endorphins. In vivo
      studies suggest differential activity of endogenous opioid receptors in rodents
      with high and low alcohol preference. Similarly, humans with a family history of
      alcohol dependence also show a heightened endorphin response to an acute
      challenge of alcohol compared with those with no family history of alcohol
      dependence.The effects of opioid agonists and antagonists on rodent and human
      alcohol consumption further support the opioid-alcohol link. In rodents and
      humans, small doses of opioid agonists increase alcohol consumption, while
      pretreatment with large doses decreases consumption. The opioid antagonist
      naltrexone decreases rodent alcohol consumption, particularly in low doses under
      acute and intermittent schedules. Most clinical trials in patients with alcohol
      dependence support modest therapeutic effects of naltrexone in decreasing alcohol
      consumption. Efforts to identify subgroups of alcohol-dependent patients
      responsive to naltrexone, as well as psychosocial and pharmacological
      augmentation strategies, may further improve the clinical usefulness of the drug.

PMID- 16097854
TI  - Extended-release carbamazepine capsules: a viewpoint.

PMID- 16097855
TI  - Interferon-alpha treatment of patients with Hepatitis C: the role of a
      comprehensive risk-benefit assessment.

PMID- 16097857
TI  - Partial dehydration of the retinal binding pocket and proof for photochemical
      deprotonation of the retinal Schiff base in bicelle bacteriorhodopsin crystals.
AB  - In bicelle bacteriorhodopsin (bcbR) crystals, the protein has a different
      structure from both native bacteriorhodopsin (bR) and in-cubo bR (cbR) crystals.
      Recently, we studied the ability of bcbR crystals to undergo the photocycle upon
      laser excitation, characterized by the appearance of the M intermediate by single
      crystal resonance Raman spectroscopy. Calculation of the M lifetime by flash
      photolysis experiments demonstrated that in our bcbR crystals, the M rise time is
      much faster than in the native or cbR crystals, with a decay time that is much
      slower than these other two forms. Although it is now known that the bcbR
      crystals are capable of photochemical deprotonation, it is not known whether
      photochemical deprotonation is the only way to create the deprotonated Schiff
      base in the bcbR crystals. We measured both the visible and Raman spectra of
      crystals dried under ambient lighting and dried in the dark in order to determine
      whether the retinal Schiff base is able to thermally deprotonate in the dark. In
      addition, changes in the visible spectrum of single bcbR crystals under varying
      degrees of hydration and light exposure were examined to better understand the
      retinal binding environment.

PMID- 16097858
TI  - Photophysics of aminoxanthone derivatives and their application as binding probes
      for DNA.
AB  - Xanthones with amino substituents were synthesized to diminish the
      photoreactivity of the xanthone chromophore with DNA, with the objective of using
      these molecules to study their binding dynamics with DNA. The aminoxanthones
      showed a strong solvatochromic effect on their singlet and triplet excited-state
      photophysics, where polar solvents led to a decrease of the energies for the
      excited states. Quenching of the triplet excited states by nitrite anions was
      used to determine the binding dynamics, and a residence time in the microsecond
      time domain was estimated for the bound 2-aminoxanthone with DNA. The quenching
      experiments performed showed that this methodology will not be applicable to
      study the binding dynamics of a wide variety of guests with DNA.

PMID- 16097859
TI  - A photodissociation reaction: Experimental and computational study of 2-hydroxy
      2,2-dimethylacetophenone.
AB  - The photophysical parameters controlling the cleavage process of 2-hydroxy-2,2
      dimethylacetophenone (HDMA) were investigated in detail. Time-resolved picosecond
      absorption experiments show that the formation of the triplet state occurs within
      20 ps after excitation and decays within hundreds of picoseconds depending on the
      solvent polarity. Molecular modeling reveals that three stable conformations
      exist in the ground state, the most stable one exhibiting an intramolecular
      hydrogen bond that modifies the electronic properties of the molecule. This
      explains quite well the steady-state absorption properties. The conformation of
      the most stable triplet state is twisted by 180 degrees with respect to the
      ground state. Computation of the potential energy surface along the molecular
      coordinate for the dissociation reaction evidences an electronic state crossing
      yielding a final sigmasigma* state, in perfect agreement with the state
      correlation diagram. Optimization of the transition state allows the calculation
      of the activation energy and the use of the transition-state theory leads to an
      estimate of 100 ps for the cleavage process in the gas phase. Single-point energy
      calculations using a solvent model predict an increase of the dissociation rate
      constant with the increase of the solvent polarity, in good agreement with the
      value deduced from kinetic measurements.

PMID- 16097860
TI  - Photoreduction of Ru(bpy)(3)2+ by amines in aqueous solution. Kinetics
      characterization of a long-lived nonemitting excited state.
AB  - The photochemistry of Ru(bpy)(3)+2 in the presence of amines was investigated in
      water by laser flash photolysis. N,N'-Dimethylaniline and p-phenylenediamine
      quench the luminescent metal to ligand charge transfer (MLCT) excited state of
      the complex by an electron transfer reaction that produces the semireduced form
      Ru(bpy)3+ in relatively high yields. On the other hand, triethylamine (TEA) and
      aniline do not quench the MLCT. Nevertheless, when laser flash irradiation at 532
      nm is carried out in the presence of these amines, the formation of Ru(bpy)3+ is
      clearly detected by its transient absorption at 510 nm. These results are
      interpreted by an electron transfer reaction with the participation of a
      nonemitting excited state of the complex, formed independently of the MLCT from
      the Franck-Condon or the relaxed singlet excited state. The rate constants for
      the quenching of this state by TEA and aniline and the quantum yields for
      Ru(bpy)(3)+ were determined. The new state is formed in a very fast process and
      has a lifetime of ca 4 micros in water.

PMID- 16097861
TI  - Cellular and antitumor activity of a new diethylene glycol benzoporphyrin
      derivative (lemuteporfin).
AB  - A newly synthesized diethylene glycol functionalized chlorin-type
      photosensitizer, lemuteporfin, was characterized for use in photodynamic therapy
      (PDT) in a panel of in vitro and in vivo test systems. The photosensitizer was
      highly potent, killing cells at low nanomolar concentrations upon exposure to
      activating light. The cellular uptake of lemuteporfin was rapid, with maximum
      levels reached within 20 min. Mitogen-activated lymphoid cells accumulated more
      of the lemuteporfin than their quiescent equivalents, supporting selectivity.
      Photosensitizer fluorescence in the skin increased rapidly within the first few
      minutes following intravenous administration to mice, then decreased over the
      next 24 h. Skin photosensitivity reactions indicated rapid clearance of the
      photosensitizer. Intravenous doses as low as 1.4 micromol/kg combined with
      exposure to 50 J/cm2 red light suppressed tumor growth in a mouse model. In
      conclusion, this new benzoporphyrin was found to be an effective photosensitizer,
      showing rapid uptake and clearance both in vitro and in vivo. This rapid
      photosensitization of tumors could be useful in therapies requiring a potent,
      rapidly accumulating photosensitizer, while minimizing the potential for skin
      photosensitivity reactions to sunlight following treatment.

PMID- 16097862
TI  - Timing and velocity randomization similarly affect anticipatory pursuit.
AB  - Smooth pursuit eye movements are guided largely by retinal-image motion. To
      compensate for neural conduction delays, the brain employs a predictive mechanism
      to generate anticipatory pursuit that precedes target motion (E. Kowler, 1990). A
      critical question for interpreting neural signals recorded during pursuit
      concerns how this mechanism is interfaced with sensorimotor processing. It has
      been shown that the predictor is not simply turned-off during randomization
      because anticipatory eye velocity remains when target velocity is randomized (E.
      Kowler & S. McKee, 1987; G. W. Kao & M. J. Morrow, 1994). This study was
      completed to compare pursuit behavior during randomized motion-onset timing with
      that occurring during direction or speed randomization. We found that
      anticipatory eye velocity persisted despite motion-onset randomization, and that
      anticipation onset time was between that observed in the different constant
      timing conditions. This centering strategy was similar to the bias of eye
      velocity magnitude away from extremes observed when direction or speed was
      randomized. Such a strategy is comparable to least-squares error minimization,
      and could be used to facilitate acquisition of a target when it begins to move.
      Centering was in some observers accounted for by a shift of eye velocity toward
      that generated in the preceding trial. The results make unlikely a model in which
      the predictor is disengaged by randomizing stimulus timing, and suggest that
      predictive signals always interact with those used in sensorimotor processing
      during smooth pursuit.

PMID- 16097863
TI  - Is prior knowledge of object geometry used in visually guided reaching?
AB  - We investigated whether humans use prior knowledge of the geometry of faces in
      visually guided reaching. When viewing the inside of a mask of a face, the mask
      is often perceived as being a normal (convex) face, instead of the veridical,
      hollow (concave) shape. In this "hollow-face illusion," prior knowledge of the
      shape of faces dominates perception, even when in conflict with information from
      binocular disparity. Computer images of normal and hollow faces were presented,
      such that depth information from binocular disparity was consistent or in
      conflict with prior knowledge of the geometry. Participants reached to touch
      either the nose or cheek of the faces or gave verbal estimates of the
      corresponding distances. We found that reaching to touch was dominated by prior
      knowledge of face geometry. However, hollow faces were estimated to be flatter
      than normal faces. This suggests that the visual system combines binocular
      disparity and prior assumptions, rather than completely discounting one or the
      other. When comparing the magnitude of the hollow-face illusion in reaching and
      verbal tasks, we found that the flattening effect of the illusion was similar for
      verbal and reaching tasks.

PMID- 16097864
TI  - Depth information affects judgment of the surface-color mode appearance.
AB  - The mode of color appearance is determined not solely by physical properties of
      the stimulus but also by the conditions of surrounding stimuli. Coplanar ratio
      hypothesis suggests that the information provided in the same plane plays an
      important role in the judgment of lightness. We measured the upper-limit
      luminances of the test stimulus for the surface-color mode in a three
      dimensionally represented environment to study the effects of depth and luminance
      conditions on the mode perception. The test stimulus and two array-type
      surrounding stimuli composed of 10 different colors were presented at different
      depths. The test stimulus was presented at three different depths. Subjects set
      the luminance of the test color to the point where it just ceased to appear in
      the complete surface-color mode. The upper-limit luminances of the test colors
      varied as the luminances of the surrounding stimulus displayed in the same depth
      changed. Our results indicate that the perception of the surface-color mode is
      mainly determined by the stimulus displayed in the same depth. These results
      support that belongingness--to which group in the environment the stimulus
      belongs--is important, and that the mode of color appearance is determined
      coplanar in a three-dimensional environment.

PMID- 16097865
TI  - Paucity of chromatic linear motion detectors in macaque V1.
AB  - The motion of a color-defined edge is often more difficult to perceive than the
      motion of a luminance-defined edge. Neurons subserving motion vision may
      therefore be particularly sensitive to luminance contrast. One class of neurons
      thought to play a critical role in motion perception is V1 neurons whose
      spatiotemporal receptive fields are oriented in space-time. We used the reverse
      correlation technique to study the relationship between color tuning and space
      time receptive field orientation in V1 neurons of awake, fixating monkeys.
      Neurons with space-time oriented receptive fields were tuned almost exclusively
      for luminance, whereas neurons with nonoriented space-time receptive fields were
      tuned for luminance or for color. These results suggest that the special role of
      luminance contrast in motion perception is due in part to the establishment of
      space-time oriented receptive fields among luminance-tuned, but not color-tuned,
      V1 neurons.

PMID- 16097866
TI  - Ordinal configural cues combine with metric disparity in depth perception.
AB  - Prior research on the combination of depth cues generally assumes that different
      cues must be in the same units for meaningful combination to occur. We
      investigated whether the geometrically ordinal cues of familiarity and convexity
      influence depth perception when unambiguous metric information is provided by
      binocular disparity. We used bipartite, random dot stereograms with a central
      luminance edge shaped like a face in profile. Disparity specified that the edge
      and dots on one side were closer than the dots on the other side. Configural cues
      suggested that the familiar, face-shaped region was closer than the unfamiliar
      side. Configural cues caused an increase in perceived depth for a given disparity
      signal when they were consistent with disparity and a decrease in perceived depth
      when they were inconsistent. Thus, geometrically ordinal configural cues can
      quantitatively influence a metric depth cue. Implications for the combination of
      configural and depth cues are discussed.

PMID- 16097868
TI  - Attention to locations and features: different top-down modulation of detector
      weights.
AB  - It is well known that attention improves the visibility of a target. In this
      study, we examined the effect of attention on the selectivity profile for a
      target. We used a masking technique to measure the tuning function for detecting
      a target while cueing either its orientation or its location. In the presence of
      an orientation mask, uncued thresholds were maximally elevated with a parallel
      mask and decreased with increasing mask orientation from the target. The presence
      of a cue reduced the masking effect but the shape of the function was cue
      specific: The orientation cue consistently improved thresholds at the target
      orientation, whereas the location cue typically improved thresholds at all
      orientations relative to the function measured in the absence of attention. The
      selective versus overall increase of sensitivity observed in our study may be due
      to differences in the weighting of individual detectors that determine the
      behavioral tuning function in the two cueing conditions.

PMID- 16097867
TI  - Higher order monochromatic aberrations of the human infant eye.
AB  - The monochromatic optical aberrations of the eye degrade retinal image quality.
      Any significant aberrations during postnatal development could contribute to
      infants' immature visual performance and provide signals for the control of eye
      growth. Aberrations of human infant eyes from 5 to 7 weeks old were compared with
      those of adult subjects using a model of an adultlike infant eye that accounted
      for differences in both eye and pupil size. Data were collected using the COAS
      Shack-Hartmann wavefront sensor. The results demonstrate that the higher order
      aberrations of the 5-to-7-week-old eye are less than a factor of 2 greater than
      predicted for an adultlike infant eye of this age. The data are discussed in the
      context of infants' visual performance and the signals available for controlling
      growth of the eye.

PMID- 16097869
TI  - Center-surround inhibition and facilitation as a function of size and contrast at
      multiple levels of visual motion processing.
AB  - Visual context often plays a crucial role in visual processing. In the domain of
      visual motion processing, the response to a stimulus presented to a neuron's
      classical receptive field can be modulated by presenting stimuli to its surround.
      The nature of these center-surround interactions is often inhibitory; the neural
      response decreases when the same direction of motion is presented to center and
      surround. Here we use binocular rivalry as a tool to study center-surround
      interactions. We show that magnitude of surround suppression varies as a function
      of luminance contrast and surround width. Increasing the size of surround motion
      increased surround suppression at high contrast. Furthermore, large, high
      contrast surrounds facilitated opposite-direction motion in the center. For
      stimuli presented at low contrast, surround suppression peaked at a smaller
      surround width. In addition, we provide evidence that surround inhibition occurs
      at multiple levels of visual processing: Surround inhibition in motion processing
      is likely to originate from both monocular and binocular processing stages.

PMID- 16097870
TI  - Slow feature analysis yields a rich repertoire of complex cell properties.
AB  - In this study we investigate temporal slowness as a learning principle for
      receptive fields using slow feature analysis, a new algorithm to determine
      functions that extract slowly varying signals from the input data. We find a good
      qualitative and quantitative match between the set of learned functions trained
      on image sequences and the population of complex cells in the primary visual
      cortex (V1). The functions show many properties found also experimentally in
      complex cells, such as direction selectivity, non-orthogonal inhibition, end
      inhibition, and side-inhibition. Our results demonstrate that a single
      unsupervised learning principle can account for such a rich repertoire of
      receptive field properties.

PMID- 16097871
TI  - The effect of stimulus strength on the speed and accuracy of a perceptual
      decision.
AB  - Both the speed and the accuracy of a perceptual judgment depend on the strength
      of the sensory stimulation. When stimulus strength is high, accuracy is high and
      response time is fast; when stimulus strength is low, accuracy is low and
      response time is slow. Although the psychometric function is well established as
      a tool for analyzing the relationship between accuracy and stimulus strength, the
      corresponding chronometric function for the relationship between response time
      and stimulus strength has not received as much consideration. In this article, we
      describe a theory of perceptual decision making based on a diffusion model. In
      it, a decision is based on the additive accumulation of sensory evidence over
      time to a bound. Combined with simple scaling assumptions, the proportional-rate
      and power-rate diffusion models predict simple analytic expressions for both the
      chronometric and psychometric functions. In a series of psychophysical
      experiments, we show that this theory accounts for response time and accuracy as
      a function of both stimulus strength and speed-accuracy instructions. In
      particular, the results demonstrate a close coupling between response time and
      accuracy. The theory is also shown to subsume the predictions of Pieron's Law, a
      power function dependence of response time on stimulus strength. The theory's
      analytic chronometric function allows one to extend theories of accuracy to
      response time.

PMID- 16097872
TI  - The local and global processing of chromatic Glass patterns.
AB  - Glass patterns are a valuable tool to study the cortical stages of form
      perception. We use circular Glass patterns (cGP) to study the relation between
      form and color vision. The detection of Glass patterns is thought to be carried
      out in at least two stages. In the first stage, the local orientation information
      from the pairs of dots is analyzed. A later stage integrates this local
      orientation information to yield the global percept of form. Previous work (K. S.
      Cardinal & D. C. Kiper, 2003) has shown that the second stage is chromatically
      selective, with a broad tuning in color space. Here we completed our
      characterization of the integration stage by measuring the size of the spatial
      integration area. We find that the integration area is similar to the size of V4
      receptive fields. Furthermore, we measured the chromatic selectivity and spatial
      resolution of the first stage mechanisms. First stage mechanisms are more
      selective for color than the integration stage. Their spatial resolution is
      consistent with the idea that V1/V2 neurons perform the analysis of the dot
      pairs' orientation. Our results are consistent with the idea that V1/V2 neurons
      perform the local analysis, and that spatial integration is achieved at the level
      of V4.

PMID- 16097874
TI  - Chromatic perceptive field sizes change with retinal illuminance.
AB  - The effect of retinal illuminance (0.3-3.3 log td) on chromatic perceptive field
      size was investigated at 10 degrees eccentricity along the horizontal meridian of
      the temporal retina. Using the 4+1 color-naming procedure, observers described
      the hue and saturation of a series of monochromatic stimuli (440-660 nm, in 10-nm
      steps) of various test sizes (.098-5 degrees) after 30-min dark adaptation.
      Perceptive field sizes of the four elemental hues and the saturation component
      were estimated for each wavelength at each retinal illuminance. Results indicate
      that perceptive field sizes for blue, green, yellow, and saturation all decrease
      with increasing retinal illuminance; the perceptive field size for red is the
      smallest and invariant with intensity. The influence of rods on perceptive field
      size may account for some of the results; other factors are also considered.

PMID- 16097873
TI  - The stroboscopic Pulfrich effect is not evidence for the joint encoding of motion
      and depth.
AB  - In the Pulfrich effect, an illusion of depth is produced by introducing
      differences in the times at which a moving object is presented to the two eyes.
      In the classic form of the illusion, there is a simple explanation for the depth
      percept: the interocular delay introduces a spatial disparity into the stimulus.
      However, when the moving object is viewed stroboscopically, this simple
      explanation no longer holds. In recent years, depth perception in the
      stroboscopic Pulfrich effect has been explained by invoking neurons that are
      sensitive both to stereo disparity and to direction of motion. With such joint
      motion/disparity encoders, interocular delay causes a perception of depth by
      causing a shift in each neuron's preferred disparity. This model has been
      implemented by N. Qian and R. A. Andersen (1997). Here we show that this model's
      predictions for perceived disparity are quantitatively at odds with
      psychophysical measures. The joint-encoding model predicts that the perceived
      disparity is the virtual disparity implied by the apparent motion; in fact, the
      perceived disparity is smaller. We show that the percept can be quantitatively
      explained on the basis of spatial disparities present in the stimulus, which
      could be extracted from pure disparity sensors. These results suggest that joint
      encoding of motion and depth is not the dominant neuronal basis of depth
      perception in this stimulus.

PMID- 16097875
TI  - Different sensations from cones with the same photopigment.
AB  - We used adaptive optics to study color fluctuation in the appearance of tiny
      flashes of light. For five subjects, near threshold, monochromatic stimuli with
      full widths at half maximum of 1/3 arcmin were delivered throughout a patch of
      retina near 1 deg in which we also determined the locations of L, M, and S cones.
      Subjects reported a wide variety of color sensations, even for long-wavelength
      stimuli, and all subjects reported blue or purple sensations at wavelengths for
      which S cones are insensitive. Subjects with more L cones reported more red
      sensations, and those with more M cones tended to report more green sensations.
      White responses increased linearly with the asymmetry in L to M cone ratio. The
      diversity in the color response could not be completely explained by combined L
      and M cone excitation, implying that photoreceptors within the same class can
      elicit more than one color sensation.

PMID- 16097876
TI  - Effects of contrast on smooth pursuit eye movements.
AB  - It is well known that moving stimuli can appear to move more slowly when contrast
      is reduced (P. Thompson, 1982). Here we address the question whether changes in
      stimulus contrast also affect smooth pursuit eye movements. Subjects were asked
      to smoothly track a moving Gabor patch. Targets varied in velocity (1, 8, and 15
      deg/s), spatial frequency (0.1, 1, 4, and 8 c/deg), and contrast, ranging from
      just below individual thresholds to maximum contrast. Results show that smooth
      pursuit eye velocity gain rose significantly with increasing contrast. Below a
      contrast level of two to three times threshold, pursuit gain, acceleration,
      latency, and positional accuracy were severely impaired. Therefore, the smooth
      pursuit motor response shows the same kind of slowing at low contrast that was
      demonstrated in previous studies on perception.

PMID- 16097877
TI  - The effect of ocular aberrations on steady-state errors of accommodative
      response.
AB  - It is well accepted that the accommodation system is characterized by steady
      state errors in focus. The purpose of this study was to correlate these errors
      with changes in ocular wavefront aberration and corresponding image quality when
      accommodating. A wavefront analyzing system, the Complete Ophthalmic Analysis
      System (COAS), was used in conjunction with a Badal optometer to allow continuous
      recording of the aberration structure of the eye for a range of accommodative
      demands (up to 8 D). Fifty consecutive recordings from seven subjects were taken.
      Monocular accommodative response was calculated as (i) the equivalent refraction
      minimizing wavefront error and (ii) the defocus needed to optimize the modulation
      transfer function at high spatial frequencies. Previously reported changes in
      ocular aberrations with accommodation (e.g., the shift of spherical aberration to
      negative values) were confirmed. Increased accommodation errors for near targets
      (lags) were evident for all subjects, although their magnitude showed a
      significant intersubject variability. It is concluded that the one-to-one
      stimulus/response slope in accommodation function should not always be considered
      as ideal, because higher order aberrations, especially changes of spherical
      aberration, may influence the actual accommodative demand. Fluctuations may serve
      to preserve image quality when errors of accommodation are moderate, by
      temporarily searching for the best focus.

PMID- 16097878
TI  - Bayesian inference for psychometric functions.
AB  - In psychophysical studies, the psychometric function is used to model the
      relation between physical stimulus intensity and the observer's ability to detect
      or discriminate between stimuli of different intensities. In this study, we
      propose the use of Bayesian inference to extract the information contained in
      experimental data to estimate the parameters of psychometric functions. Because
      Bayesian inference cannot be performed analytically, we describe how a Markov
      chain Monte Carlo method can be used to generate samples from the posterior
      distribution over parameters. These samples are used to estimate Bayesian
      confidence intervals and other characteristics of the posterior distribution. In
      addition, we discuss the parameterization of psychometric functions and the role
      of prior distributions in the analysis. The proposed approach is exemplified
      using artificially generated data and in a case study for real experimental data.
      Furthermore, we compare our approach with traditional methods based on maximum
      likelihood parameter estimation combined with bootstrap techniques for confidence
      interval estimation and find the Bayesian approach to be superior.

PMID- 16097879
TI  - Analyzing proteomic expression in a clinical screening environment using mass
      spectrometry.

PMID- 16097880
TI  - 53rd American Society for Mass Spectrometry Conference. 5-9 June, 2005, Henry B
      Gonzalez Conference Center, San Antonio, TX, USA.

PMID- 16097881
TI  - Peptidomics: a logical sequel to proteomics.
AB  - Rapid progress of separation techniques as well as methods of structural analysis
      provided conditions in the past decade for total screening of complex biologic
      mixtures for any given class of biomolecules. The present review updates the
      reader with the modern state of peptidomics, a chapter of chemical biology that
      deals with structure and biologic properties of sets of peptides present in
      biologic tissues, cells or fluids. Scope and limitations of currently employed
      experimental techniques are considered and the main results are outlined.
      Considerable attention will be afforded to the biologic role of peptides formed
      in vivo by proteolysis of nonspecialized precursor proteins with other well
      defined functions. In conclusion, the connection is discussed between peptidomics
      and the much more mature and still closely related field of proteomics.

PMID- 16097882
TI  - Mass spectrometry-based approaches to protein-ligand interactions.
AB  - One of the greatest current challenges in proteomics is to develop an
      understanding of cellular communication and regulation processes, most of which
      involve noncovalent interactions of proteins with various binding partners. Mass
      spectrometry plays an important role in all aspects of these research efforts.
      This article provides a survey of mass spectrometry-based approaches for
      exploring protein-ligand interactions. A wide array of techniques is available,
      and the choice of method depends on the specific problem at hand. For example,
      the high-throughput screening of compound libraries for binding to a specific
      receptor requires different approaches than structural studies on multiprotein
      complexes. This review is directed to readers wishing to obtain a concise yet
      comprehensive overview of existing experimental techniques. Specific emphasis is
      placed on emerging methods that have been developed within the last few years.

PMID- 16097883
TI  - Challenges facing the development and use of protein chips to analyze the
      phosphoproteome.
AB  - Recent advances in analytical methods, particularly in the area of protein
      microarrays, have brought the field of proteomics to the forefront of biological
      science. Protein arrays have shown to be useful for the multiplexed analysis of
      several hundreds of proteins in parallel. While much of the effort has focused on
      developing methods to identify expressed proteins, the identification of post
      translational modifications is equally important for comprehensive proteome
      characterization. Protein phosphorylation constitutes a major type of post
      translational modification that mobilizes a high number of genes, is involved in
      many crucial cell functions and largely contributes to the complexity of the
      proteome. One of the major challenges to analyze phosphoproteins using arrays is
      the availability of specific antibodies. Thus far, this has hampered the
      development of highly complex phosphoprotein arrays. This review discusses some
      of the recent progress made in the development of techniques and reagents to
      quantitatively determine sites of protein phosphorylation.

PMID- 16097884
TI  - Multiplex approaches in protein microarray technology.
AB  - The success of genome sequencing projects has provided the basis for systematic
      analysis of protein function and has led to a shift from the description of
      single molecules to the characterization of complex samples. Such a task would
      not be possible without the provision of appropriate high-throughput
      technologies, such as protein microarray technology. In addition, the increasing
      number of samples necessitates the adaptation of such technologies to a multiplex
      format. This review will discuss protein microarray technology in the context of
      multiplex analysis and highlight its current prospects and limitations.

PMID- 16097885
TI  - Structural proteomics in drug discovery.
AB  - High-throughput, automated or semiautomated methodologies implemented by
      companies and structural genomics initiatives have accelerated the process of
      acquiring structural information for proteins via x-ray crystallography. This has
      enabled the application of structure-based drug design technologies to a variety
      of new structures that have potential pharmacologic relevance. Although there
      remain major challenges to applying these approaches more broadly to all classes
      of drug discovery targets, clearly the continued development and implementation
      of these structure-based drug design methodologies by the scientific community at
      large will help to address and provide solutions to these hurdles. The result
      will be a growing number of protein structures of important pharmacologic targets
      that will help to streamline the process of identification and optimization of
      lead compounds for drug development. These lead agonist and antagonist
      pharmacophores should, in turn, help to alleviate one of the current critical
      bottlenecks in the drug discovery process; that is, defining the functional
      relevance of potential novel targets to disease modification. The prospect of
      generating an increasing number of potential drug candidates will serve to
      highlight perhaps the most significant future bottleneck for drug development,
      the cost and complexity of the drug approval process.

PMID- 16097886
TI  - Analysis of the human saliva proteome.
AB  - Interest in the characterization of the salivary proteome has increased in the
      last few years. This review discusses the different techniques and methodologies
      applied to the separation and identification of salivary proteins. Nowadays,
      proteomic techniques are the state of the art for the analysis of biologic
      materials and saliva is no exception. 2D electrophoresis and tryptic digest
      analysis by mass spectrometry are the typical methodology, but new approaches
      using 2D liquid chromatography/mass spectrometry methods have already been
      introduced for saliva analysis. Due to their important physiologic role in the
      oral cavity, low-molecular-weight proteins and peptides are also included in this
      article and the methodologies discussed.

PMID- 16097887
TI  - Building the mitochondrial proteome.
AB  - Mitochondria are essential organelles for cellular homeostasis. A variety of
      pathologies including cancer, myopathies, diabetes, obesity, aging and
      neurodegenerative diseases are linked to mitochondrial dysfunction. Therefore,
      mapping the different components of mitochondria is of particular interest to
      gain further understanding of such diseases. In recent years, proteomics-based
      approaches have been developed in attempts to determine the complete set of
      mitochondrial proteins in yeast, plants and mammals. In addition, proteomics
      based methods have been applied not only to the analysis of protein function in
      the organelle, but also to identify biomarkers for diagnosis and therapeutic
      targets of specific pathologies associated with mitochondria. Altogether, it is
      becoming clear that proteomics is a powerful tool not only to identify currently
      unknown components of the mitochondrion, but also to study the different roles of
      the organelle in cellular homeostasis.

PMID- 16097888
TI  - Developing liquid chromatography ion mobility mass spectometry techniques.
AB  - When a packet of ions in a buffer gas is exposed to a weak electric field, the
      ions will separate according to differences in their mobilities through the gas.
      This separation forms the basis of the analytical method known as ion mobility
      spectroscopy and is highly efficient, in that it can be carried out in a very
      short time frame (micro- to milliseconds). Recently, efforts have been made to
      couple the approach with liquid-phase separations and mass spectrometry in order
      to create a high-throughput and high-coverage approach for analyzing complex
      mixtures. This article reviews recent work to develop this approach for
      proteomics analyses. The instrumentation is described briefly. Several
      multidimensional data sets obtained upon analyzing complex mixtures are shown in
      order to illustrate the approach as well as provide a view of the limitations and
      required future work.

PMID- 16097889
TI  - Proteomics in hematologic malignancies.
AB  - Basic science research in hematology has been determining the functions of gene
      products using classical approaches that typically involve studying one or a few
      genes at a time. Proteomics, defined as the study of protein properties on a
      large scale, provides tools to globally analyze malignant hematologic cells. A
      major challenge in cancer therapy is the identification of drugs that kill tumor
      cells while preserving normal cells. Differential display via proteomics enables
      analysis of direct as well as side-effects of drugs at a molecular level.
      Proteomics also allows a better understanding of cell signaling pathways involved
      during apoptosis in hematologic cells. Storing the information in a 2D
      electrophoresis database enhances the efficiency of proteome research on
      malignant cells. Finally, the work needed to be carried out on proteomic analysis
      prior to routine clinical adoption is discussed, and the necessity for multi
      institutional collaborations is emphasized.

PMID- 16097890
TI  - New insights into viral structure and virus-cell interactions through proteomics.
AB  - Although genomics techniques such as DNA microarrays have been widely used in
      virology, much more limited use has been made of proteomics. Although difficult,
      proteomics can greatly contribute to an understanding of virus-cell interactions,
      including the ternary structure of viral receptors at the cell surface, post
      translational modifications and isoforms of critical viral and cellular proteins
      and even to the structure of viruses. Proteomics techniques also offer the
      potential for discovering markers for diagnostic and prognostic tests of viral
      infections in vivo. This review describes the use of several proteomic approaches
      for the analysis of HIV-cellular receptor interactions, the molecular mechanisms
      of transport of herpes simplex virus within neurons, and the structure of the
      tegument of herpes simplex virus.

PMID- 16097891
TI  - Current progress in proteomic study of hepatitis C virus-related human
      hepatocellular carcinoma.
AB  - Chronic infection with hepatitis C virus (HCV) is known to be a risk factor for
      not only cirrhosis and steatosis but also hepatocellular carcinoma (HCC). A
      number of diagnostic and prognostic molecular markers are being identified by
      transcriptomic and proteomic analysis of HCC today. However, the analyses are
      performed on HCC in general, and the studied tissues are HCV infected, HBV
      infected, infected with both or neither, or the infection status may be unknown.
      The authors performed proteomic analysis of cancerous and noncancerous tissues
      from HCC patients with HCV infection, and determined that, in the cancerous
      tissues, HSP70 family proteins such as GRP78, HSC70, GRP75 and HSP70.1, glutaine
      synthetase isoforms, HSP60, alpha-enolase, phosphoglycerate mutase 1, ATP
      synthetase beta chain and triosephosphate isomerase were increased whereas
      albumin, ferritin light chain, smoothelin, tropomyosin beta chain, arginase 1,
      aldolase B and kietohexokinase were decreased. The aim of this study is to
      understand the pathogenesis of HCV-HCC using proteomic analysis of samples from
      HCV-HCC patients on which transcriptomics has already been performed.

PMID- 16097892
TI  - Proteomic identification of biomarkers of traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a major national health problem without a US Food
      and Drug Administration-approved therapy. This review summarizes the importance
      of discovering relevant TBI protein biomarkers and presents logical rationale
      that neuroproteomic technologies are uniquely suited for the discovery of
      otherwise unnoticed TBI biomarkers. It highlights that one must make careful
      decisions when choosing which paradigm (human vs. animal models) and which
      biologic samples to use for such proteomic studies. It further outlines some of
      the desirable attributes of an ideal TBI biomarker and discusses how biomarkers
      discovered proteomically are complementary to those identified by traditional
      approaches. Lastly, the most important sequela of any proteomically identified
      TBI biomarker is validation in preclinical or clinical samples.

PMID- 16097893
TI  - Cell cycle: proteomics gives it a spin.
AB  - The eukaryotic cell division cycle has been studied at the molecular level for
      over 30 years, most fruitfully in model organisms. In the past 5 years,
      developments in mass spectrometry-based proteomics have been applied to the study
      of protein interactions and post-translational modifications involving key cell
      cycle regulators such as cyclin-dependent kinases and the anaphase-promoting
      complex, as well as effectors such as centrosomes, the kinetochore and DNA
      replication forks. In addition, innovations in chemical biology, functional
      proteomics and bioinformatics have been employed to study the cell cycle at the
      proteome level. This review surveys the contributions of proteomics to cell cycle
      research. The near future should see the application of more quantitative
      proteomic approaches to probe the dynamic aspects of the molecular system that
      underlie the cell cycle in model organisms and in human cells.

PMID- 16097900
TI  - A randomized pilot study of cognitive-behavioral therapy versus basic health
      education for smoking cessation among cancer patients.
AB  - BACKGROUND: Previously, we have linked theoretically based cognitive and
      emotional variables to the ability of cancer patients to quit smoking. PURPOSE:
      In this study, we evaluated the impact of cognitive-behavioral therapy (CBT),
      which addressed these theoretically derived cognitive and emotional variables
      linked to tobacco use in this population, for promoting smoking cessation in a
      sample of cancer patients and assessed longitudinal predictors of smoking
      cessation. METHODS: Cancer patients (N=109) were randomized to either the
      theoretically based CBT intervention or to a general health education (GHE)
      condition, and all patients received nicotine replacement therapy. RESULTS:
      Contrary to our expectation, no significant difference in 30-day point-prevalence
      abstinence between the CBT and GHE conditions was detected at either a 1-month
      (44.9 vs. 47.3%, respectively) or 3-month (43.2% vs. 39.2%, respectively) follow
      up evaluation. Higher quit motivation and lower cons of quitting were related to
      smoking cessation. CONCLUSIONS: Implications for the implementation of smoking
      cessation behavioral treatments in the oncologic context are discussed, as are
      directions for future research in this area.

PMID- 16097901
TI  - Longitudinal relationships among transtheoretical model constructs for smokers in
      the precontemplation and contemplation stages of change.
AB  - BACKGROUND: This study examined the pattern, direction, and magnitude of
      longitudinal relationships among the constructs involved in the Transtheoretical
      Model (TTM). PURPOSE: The goal was to explore within-TTM relationships to create
      an integrated structural model that adequately represents the change process.
      METHOD: Data were collected as part of a representative general adult population
      study in Germany. A total of 688 smokers in the precontemplation and
      contemplation stages of change were assessed two times, 6 months apart, with
      respect to the TTM constructs. Structural equation modeling was used and a step
      approach was employed to evaluate the relationships between cognitive-affective
      processes, behavioral processes, the pros and cons of smoking, and self-efficacy,
      stratified for baseline stage of change. RESULTS: The model-building process
      resulted in two final structural equation models detailing longitudinal TTM
      relationships for precontemplation and contemplation. A structural invariance
      test showed that the precontemplation model also held for the contemplation
      sample and visa versa. CONCLUSIONS: The TTM constructs can be integrated in a
      longitudinal structural model. The findings provide empirical support for
      specific relationships that are posited in the TTM framework. However, differing
      relationships between TTM constructs for precontemplation and contemplation could
      not be established.

PMID- 16097902
TI  - Physical activity and sedentary behaviors in adolescents.
AB  - BACKGROUND AND PURPOSE: The main goal of this study was to address two questions:
      How is physical activity affected by sedentary behavior (computer, television,
      and commuting), and how are physical activity characteristics (intensity,
      frequency, type) different based on adolescents reports of physical activity?
      METHODS: The sample comprised 230 girls and 220 boys 14.6 years of age. Physical
      activity (PA) was assessed by questionnaire. Based on previously published
      standards, participants were grouped into the nonactive group, which included
      both sedentary and low active youth, and the active group, which included the
      moderately and vigorously active youth. Another questionnaire about leisure
      activities was applied to define the nature of PA. Sedentary behaviors, such as
      television viewing and computer use (weekday and weekend), and commuting to and
      from school (passive vs. active) were analyzed. RESULTS: Significantly more girls
      (p<or=.000) belonged to the inactive group (71.7%) than boys. The active
      participants reported being significantly more engaged in moderate intensity
      (49.1%; p<.000), moderate frequency (55.6%; p<.001), and team activities (62.0%;
      p<.005) than inactive participants. In addition, active participants reported
      significantly more participation in organized sports (21.6% vs. 5.2%) and in both
      activities (organized and individual activities; 45.5% vs. 3.9%) than nonactive
      counterparts. Our data show that active versus inactive groups did not differ on
      television watching on weekdays or on commuting. However, active participants
      were less likely to watch television on the weekends than inactive participants.
      Logistic regression showed that computer use during weekdays was a predictor of
      PA. An increase in computer use time (from 1 hr to 2-3 hr/day) was associated a
      higher PA. CONCLUSIONS: Sedentary behaviors such as television viewing or
      computer use might have different value in relation to PA for youth.

PMID- 16097903
TI  - Exercise slips in high-risk situations and activity patterns in long-term
      exercisers: an application of the relapse prevention model.
AB  - BACKGROUND: Key factors in successful long-term exercise maintenance are not well
      understood. The Relapse Prevention Model (RPM) may provide a framework for this
      process. PURPOSE: The purpose of this study was to examine the relationships
      among characteristics of exercise high-risk situations, components of the RPM
      relevant to exercise slips, and follow-up exercise outcomes in long-term
      community exercisers. METHODS: We obtained long-term exercisers' (N=65) open
      ended responses to high-risk situations and ratings of obstacle self-efficacy,
      guilt, and perceived control. High-risk situation characteristics, cognitive and
      behavioral coping strategies, and exercise outcomes were examined. RESULTS: High
      risk situation characteristics included bad weather, inconvenient time of day,
      being alone, negative emotions, and fatigue. Being alone was associated with
      lower incidence of exercise slip. Positive cognitive coping strategies were most
      commonly employed and were associated with positive exercise outcome for both
      women and men. Guilt and perceived control regarding the high-risk situation were
      associated with exercise outcomes at follow-up, but only among the men (n=28).
      CONCLUSIONS: Findings confirm and extend previous work in the application of the
      RPM in examining exercise slips and relapse. Measurement issues and integration
      approaches from the study of relapse in addiction research are discussed.

PMID- 16097904
TI  - Marital-role quality and stress-related psychobiological indicators.
AB  - BACKGROUND: The quality of one's marital relationship is gaining recognition as a
      potential stressor associated with negative health outcomes. PURPOSE: In this
      study, we estimated the relationship between marital-role quality and three
      psychobiological stress indicators (self-reported stress, cortisol levels, and
      ambulatory blood pressure). METHOD: Participants were 105 middle-age adults (67
      men, 38 women) who had previously taken part in the Whitehall psychobiology
      study. Ambulatory monitoring and saliva sampling were carried out over a working
      day, and marital relationships were assessed with the Marital/Partner Role
      Quality scales. RESULTS: We found that marital-role concerns (but not marital
      role rewards) were related to all three psychobiological stress indicators;
      results did not vary by gender. Specifically, participants with more marital
      concerns reported greater stress throughout the day (p=.014), showed an
      attenuated cortisol increase following waking (p=.042) and a flatter cortisol
      slope over the day (p=.010), and had elevated ambulatory diastolic blood pressure
      over the middle of the workday (p=.004), with a similar trend in systolic
      pressure (p=.069). CONCLUSIONS: The results suggest that in addition to the
      carryover of work stress into domestic life that has been evident for many years,
      there are also influences of domestic strain on biological function over the
      working day and evening. Previous research suggests that a possible mechanism
      linking troubled marriages to health outcomes is depressed immune functioning.
      This study suggests a second mechanism-poorer stress-related biological response.

PMID- 16097905
TI  - Styles of emotion regulation and their associations with perceived health in
      patients with rheumatoid arthritis.
AB  - BACKGROUND: Patients with rheumatoid arthritis face the challenge of adjusting to
      adverse health consequences and accompanying emotions. Styles of emotion
      regulation may affect health. PURPOSE: The objective is to examine associations
      between styles of emotion regulation and perceived health, consisting of
      psychological well-being, social functioning, physical functioning, and disease
      activity. METHODS: Principal component analysis was used to summarize styles of
      emotion regulation of 335 patients with rheumatoid arthritis. Relationships
      between emotion regulation and perceived health were examined with structural
      equation modeling. RESULTS: Four styles of emotion regulation were identified:
      ambiguity, control, orientation, and expression. Ambiguity and control were
      mutually correlated, as were orientation and expression. Styles of emotion
      regulation were not uniquely related to perceived physical functioning and
      disease activity. Emotional ambiguity and orientation were related to poorer,
      whereas expression and control were related to more favorable psychological well
      being and social functioning. CONCLUSIONS: Our cross-sectional study suggests
      that emotion regulation is not of direct importance for perceived somatic health
      of patients with rheumatoid arthritis, but it may be of importance for
      psychological well-being and social functioning, and perhaps through this route
      for somatic health. The more conscious and controlled aspects of control and
      expression are positively related to psychosocial health, and the more
      unconscious automatic aspects of ambiguity and orientation are negatively
      related. Changing emotion regulation will potentially affect psychosocial health.
      It would be worthwhile to verify this possibility in prospective research.

PMID- 16097906
TI  - Randomized pilot of a self-guided internet coping group for women with early
      stage breast cancer.
AB  - BACKGROUND: Internet-based methods for provision of psychological support and
      intervention to cancer survivors hold promise for increasing the public impact of
      such treatments. PURPOSE: The goal of this controlled pilot study was to examine
      the effect and potential mechanisms of action of a self-guided, Internet-based
      coping-skills training group on quality of life outcomes in women with early
      stage breast cancer. METHODS: Sixty-two women completed baseline evaluations and
      were randomized into either a small online coping group or a waiting-list control
      condition. RESULTS: No main effects for treatment were observed at the 12-week
      follow up. However, there was a significant interaction between baseline self
      reported health status and treatment, such that women with poorer self-perceived
      health status showed greater improvement in perceived health over time when
      assigned to the treatment condition. Linguistic analyses revealed that positive
      changes across quality of life variables were associated with greater expression
      of negative emotions such as sadness and anxiety, greater cognitive processing,
      and lower expression of health-related concerns. CONCLUSIONS: These results
      demonstrate the potential efficacy of self-guided Internet coping groups while
      highlighting the limitations of such groups.

PMID- 16097907
TI  - A strategy for optimizing and evaluating behavioral interventions.
AB  - BACKGROUND: Although the optimization of behavioral interventions offers the
      potential of both public health and research benefits, currently there is no
      widely agreed-upon principled procedure for accomplishing this. PURPOSE: This
      article suggests a multiphase optimization strategy (MOST) for achieving the dual
      goals of program optimization and program evaluation in the behavioral
      intervention field. METHODS: MOST consists of the following three phases: (a)
      screening, in which randomized experimentation closely guided by theory is used
      to assess an array of program and/or delivery components and select the
      components that merit further investigation; (b) refining, in which interactions
      among the identified set of components and their interrelationships with
      covariates are investigated in detail, again via randomized experiments, and
      optimal dosage levels and combinations of components are identified; and (c)
      confirming, in which the resulting optimized intervention is evaluated by means
      of a standard randomized intervention trial. To make the best use of available
      resources, MOST relies on design and analysis tools that help maximize
      efficiency, such as fractional factorials. RESULTS: A slightly modified version
      of an actual application of MOST to develop a smoking cessation intervention is
      used to develop and present the ideas. CONCLUSIONS: MOST has the potential to
      husband program development resources while increasing our understanding of the
      individual program and delivery components that make up interventions.
      Considerations, challenges, open questions, and other potential benefits are
      discussed.

PMID- 16097908
TI  - Relationship of socioeconomic markers to daily life ischemia and blood pressure
      reactivity in coronary artery disease patients.
AB  - BACKGROUND: Socioeconomic status (SES) is an important predictor of clinical
      outcomes in patients with coronary artery disease (CAD). PURPOSE: We hypothesized
      that a selected sample of low SES cardiac patients would display heightened
      cardiovascular stress responses in the laboratory and increased daily life
      ischemia compared to otherwise comparable higher SES patients. METHODS: Eighty
      two patients (M age=61.8+/-9.4 years; 71 men, 11 women) with a known history of
      CAD engaged in a stressful mental arithmetic task while blood pressure (BP)
      measures were collected. Myocardial ischemia was subsequently assessed via 48-hr
      ambulatory electrocardiographic monitoring in a subgroup of 51 patients. SES was
      defined by participants' residential block groups, which were linked to Census
      Bureau data about their neighborhood, including per capita income, percentage of
      the population below poverty, educational level, as well as self-report of number
      of years of education. RESULTS: Contrary to expectation, high SES participants in
      the study displayed higher diastolic BP (p<.01) and systolic BP (p<.001)
      responses to mental stress in the laboratory. CONCLUSIONS: Participants with
      daily life ischemia came from wealthier neighborhoods using indexes of poverty
      (p<.01), income (p<.02), and education (p<.04) compared to patients without
      ambulatory ischemia. This relationship was not accounted for by age, sex, race,
      body mass index, marital status, or measures of disease severity.

PMID- 16097909
TI  - Interactive effects of anger expression and ET-1 Lys198Asn polymorphism on
      vasoconstriction reactivity to behavioral stress.
AB  - BACKGROUND: Ineffective anger expression has been associated with essential
      hypertension (EH) and with blood pressure (BP) reactivity to stress. The ET
      1/Lys198Asn polymorphism has been associated with increased resting BP and
      exaggerated vasoconstrictive mediated BP reactivity. African Americans (AAs) are
      at particular risk for development of EH, report greater anger difficulties, and
      exhibit greater vasoconstrictive reactivity than their European American (EA)
      counterparts. PURPOSE: The objective is to investigate a gene-environment model
      of stress reactivity in which anger expression, particularly in combination with
      ET-1 T allele carrier status and AA ethnicity, would be associated with the
      greatest vasoconstrictive reactivity in response to a behavioral stressor.
      METHODS: One hundred ninety-one AA and 197 EA normotensive young adults (M
      age=18.8+/-2.5 years) participated in the study. Total peripheral resistance
      index (TPRI) reactivity was assessed during a 10-min video game challenge. Anger
      expression was measured using Spielberger's Anger Expression Scale. RESULTS: A
      multiple regression model with TPRI reactivity as the dependent variable revealed
      a three-way interaction effect for anger management (i.e., AM=anger control minus
      anger out scores), ethnicity, and ET-1 polymorphism. Specifically, AA carriers of
      the ET-1 polymorphism with poor AM skills exhibited the greatest TPRI reactivity.
      CONCLUSIONS: Individuals with a genetic predisposition for exaggerated
      vasoconstriction who also display low AM skills may be at particular risk for
      development of stress-induced EH. Such individuals may particularly benefit from
      anger management training.

PMID- 16097910
TI  - Syphilis: back on the rise, but not unstoppable.
AB  - Fighting the current epidemic requires intensive education of clinicians and men
      who have sex with men, as well as targeted screening.

PMID- 16097911
TI  - Non-conventional approaches to allergy testing: reconciling patient autonomy with
      medical practitioners' concerns.
AB  - It may be difficult for patients to distinguish current concepts of immune
      function from other, non-conventional explanations of illness.

PMID- 16097912
TI  - Mainstreaming the metabolic syndrome: a definitive definition.
AB  - This new definition should assist both researchers and clinicians.

PMID- 16097913
TI  - Epidemic syphilis among homosexually active men in Sydney.
AB  - OBJECTIVES: To describe trends in the notification of infectious syphilis in New
      South Wales, the characteristics of homosexually active men recently notified
      with early syphilis, and the seroprevalence and incidence of syphilis, as well as
      associated risk factors, in a Sydney cohort of HIV-negative homosexually active
      men. DESIGN, SETTING AND PARTICIPANTS: Secondary analysis of New South Wales
      infectious syphilis surveillance data from 1998 to 2003; a case series of 57
      homosexually active men diagnosed with early syphilis in inner Sydney from
      December 2002 to January 2004; and a prospective cohort study of syphilis among
      1333 HIV-negative homosexually active men in Sydney recruited from June 2001 to
      December 2003. MAIN OUTCOME MEASURES: Rates of notification of infectious
      syphilis in New South Wales and in areas of inner Sydney; behavioural and
      clinical features of men with syphilis in the case series; and incidence of
      syphilis and hazard ratios (HRs) associated with sexual behaviours in the cohort
      study. RESULTS: Infectious syphilis notifications in inner Sydney rose more than
      10-fold (from 6 in 1999 to 162 in 2003), and the increase was confined to men. Of
      57 men with early syphilis in the case series, 54% were HIV-positive and 32%
      reported no symptoms of syphilis. These 57 men were highly sexually active and
      likely to report recreational drug use. In the cohort study, 1292 men (97% of
      participants) consented to syphilis testing; the incidence of syphilis was 0.78
      per 100 person-years, and risk factors included reporting unprotected anal
      intercourse with HIV-positive partners (HR, 5.31; 95% CI, 2.00-184.93) and
      insertive oral sex (HR, 4.55; 95% CI, 1.14-18.18). CONCLUSION: Syphilis has been
      re-established among homosexually active men in Sydney, and HIV-positive men are
      over-represented. Frequent screening is needed in this population to curb the
      transmission of both syphilis and HIV.

PMID- 16097914
TI  - Effects of asbestos and smoking on gas diffusion in people exposed to
      crocidolite.
AB  - OBJECTIVE: To examine the effects of asbestos exposure and tobacco smoking on the
      level and rate of change of the diffusing capacity of the lung for carbon
      monoxide (DLCO). DESIGN AND PARTICIPANTS: A cohort study of 934 people (including
      both mine workers and town residents) exposed to crocidolite (blue asbestos) at
      the asbestos mines and in the town of Wittenoom, Western Australia, between 1943
      and 1966. DLCO measurements were taken during a follow-up period from 1992 to
      2002. MAIN OUTCOME MEASURES: Baseline levels of DLCO and change in levels over
      time. RESULTS: 2980 DLCO measurements were done on 934 people (of whom 818 were
      men and 724 were workers) who underwent a median of 2 (range, 1-17) measurements
      during the follow-up period. Radiographic asbestosis at baseline and asbestos
      exposure at a younger age were associated with lower DLCO values. The average
      rate of decline in DLCO was 0.33 (95% CI, 0.31-0.35) units per year, plus an
      additional decrement of 0.22 (95% CI, 0.12-0.32) units per year if the
      participant had radiographic asbestosis at the beginning of the follow-up period.
      Compared with never-smokers, current smokers and ex-smokers had lower DLCO at
      baseline, but smoking status did not affect the change in DLCO during the follow
      up period. CONCLUSIONS: Our results confirm a continuous deleterious effect of
      crocidolite on DLCO, especially on people with asbestosis. Smoking was associated
      with lower DLCO levels, but was not a significant predictor of rate of change in
      DLCO. Smoking status did not affect the relationships between crocidolite
      exposure and the level or rate of change of DLCO in this population.

PMID- 16097915
TI  - Australia's media reporting of health and medical matters: a question of quality.
AB  - Reporting medical news entails a special responsibility.

PMID- 16097916
TI  - Monitoring the quality of medical news reporting: early experience with media
      doctor.
AB  - OBJECTIVE: To analyse the reviews of medical news articles posted on media
      doctor, a medical news-story monitoring website. DESIGN AND SETTING: A
      descriptive summary of operating the media doctor website between 1 February and
      1 September 2004. MAIN OUTCOME MEASURES: Consensus scores for 10 assessment
      criteria for the medical intervention described in the article (novelty,
      availability in Australia, alternative treatment options given, evidence of
      "disease mongering", objective supportive evidence given, quantification of
      benefits, coverage of harms, coverage of costs, independent sources of
      information, and excessive reliance on a press release); cumulative article
      rating scores for major media outlets. RESULTS: 104 news articles were featured
      on media doctor in the study period. Both online and print media scored poorly,
      although the print media were superior: mean total scores 56.1% satisfactory for
      print and 40.1% for online; percentage points difference 15.9 (95% CI, 8.3-23.6).
      The greatest differences were seen for the use of independent information
      sources, quantification of benefits and coverage of potential harms. CONCLUSIONS:
      Australian lay news reporting of medical advances, particularly by the online
      news services, is poor. This might improve if journals and researchers became
      more active in communicating with the press and the public.

PMID- 16097917
TI  - Evidence-based journalism: a forlorn hope?
AB  - Media outlets have as much responsibility as ever to maintain standards.

PMID- 16097918
TI  - New website is no miracle cure.

PMID- 16097919
TI  - Medical news reporting: establishing goodwill and cooperation.

PMID- 16097920
TI  - Attitudes of oncology health professionals to information from the Internet and
      other media.
AB  - OBJECTIVE: To investigate attitudes of Australian health professionals working in
      oncology to health-related information in the media and on the Internet and to
      patients who search for this information. DESIGN: Questionnaire-based survey.
      SETTING AND PARTICIPANTS: Questionnaires were mailed in January 2003 to all 333
      health professionals belonging to the Victorian Cooperative Oncology Group. MAIN
      OUTCOME MEASURES: 27 items about attitudes to information in the media and the
      Internet, patient information-seeking and its effects on the doctor-patient
      relationship. RESULTS: 226 surveys (68%) were returned and assessable. Most
      respondents took notice of medical information reported on television/radio, in
      newspapers (80% each) and on the Internet (56%), mainly to be informed when
      patients ask questions (82%) and to check its accuracy (60%). Most were concerned
      about this accuracy (64% believed it accurate only sometimes, and 23% rarely),
      and 91% believed information from the Internet had the potential to cause harm to
      patients. Nevertheless, they generally supported patients' information-searching,
      believing it allowed them to be better informed (58%), and did not affect their
      ability to cope with their illness (49%), or their trust in, and relationship
      with, their doctor (69% and 67%, respectively). CONCLUSIONS: Oncology health
      professionals are aware of patients' use of the Internet and other media to
      obtain medical information. To ensure oncology patients find reliable and
      relevant information and to minimise the risk of harm, the health professionals
      treating them should provide guidance in finding information sources, and
      assistance in interpreting the information obtained.

PMID- 16097921
TI  - Phaeochromocytoma: current concepts.
AB  - The discovery of novel mutations in genes encoding succinate dehydrogenase
      subunits has revealed that familial phaeochromocytomas are much more common than
      previously thought. Genetic screening should be offered to patients with
      apparently sporadic phaeochromocytomas and their first-degree relatives. An
      increasing proportion of phaeochromocytomas present preclinically on genetic
      testing or as "incidentalomas" on abdominal imaging, rather than with classic
      symptoms and signs. Clinical suspicion should prompt measurement of plasma levels
      of free metanephrine or 24-hour urinary catecholamine and metanephrine levels,
      followed, if positive, by tumour localisation studies. With appropriate
      perioperative care, surgical management of phaeochromocytomas is safe and
      effective. Most tumours can be removed laparoscopically.

PMID- 16097922
TI  - Tumour necrosis factor inhibitors.
AB  - The cytokine, tumour necrosis factor-alpha (TNF-alpha) plays a key role in the
      pathogenesis of many chronic inflammatory and rheumatic diseases, in particular,
      Crohn's disease, rheumatoid arthritis, ankylosing spondylitis and psoriatic
      arthritis. Controlled trials have shown that the TNF inhibitors (etanercept,
      infliximab and adalimumab) significantly reduce symptoms and signs, improve
      function and quality of life, and reduce radiologically evident damage in
      patients with rheumatoid diseases. For reasons that are not entirely clear,
      etanercept does not work in Crohn's disease. Injection site and intravenous
      reactions and increased risk of infection (in particular, reactivation of
      tuberculosis) are associated with the use of these agents. Increased risk of
      lymphoproliferative disease, the development of lupus-like syndromes and
      demyelination, including optic neuritis and reactivation of multiple sclerosis,
      are under evaluation in long-term follow-up studies. The TNF inhibitors are
      expensive (about $18 000 per year), and in some patients need to be given
      continuously to maintain benefit, even in the presence of other immunosuppressive
      therapy.

PMID- 16097923
TI  - Maintaining an agenda for children: the role of data in linking policy, politics
      and outcomes.
AB  - There is growing recognition in Australia of the importance of early childhood to
      later health and wellbeing, with developments such as the National Agenda for
      Early Childhood and the National Public Health Action Plan for Children. To
      sustain a policy agenda for children and improve long-term outcomes, we need
      timely, comprehensive and accurate indicators and data on child health,
      development and wellbeing. Building this evidence requires a national monitoring
      and surveillance system that involves more than aggregating or linking existing
      data. Steps to building a national system are: to agree on key indicators of
      child health, development and wellbeing for regular reporting, to research a
      comprehensive set of indicators for each domain and ascertain data gaps, and to
      ensure development and coordination of data relevant to policy-making.

PMID- 16097924
TI  - Fit for a fracture.

PMID- 16097925
TI  - Locally acquired lymphogranuloma venereum in a bisexual man.

PMID- 16097926
TI  - Sustained increase in infectious syphilis notifications in Victoria.

PMID- 16097927
TI  - A potential link between magnesium intake and diabetes in Indigenous Australians.

PMID- 16097928
TI  - Spontaneous bruising, haematomata and prolonged APTT with meloxicam.

PMID- 16097929
TI  - Venous thromboembolism: diagnosis and management of pulmonary embolism.

PMID- 16097930
TI  - Screening for venous thrombosis by ultrasonography before hospital discharge
      after major joint surgery.

PMID- 16097931
TI  - Familial hypercholesterolaemia: a look back, a look ahead.

PMID- 16097932
TI  - A picture of Australia's children.

PMID- 16097933
TI  - Physical examination: bewitched, bothered and bewildered.

PMID- 16097934
TI  - Chemotaxis in the green flagellate alga Chlamydomonas.
AB  - Behavior of the green flagellate alga Chlamydomonas changes in response to a
      number of chemical stimuli. Specific sensitivity of the cells to different
      substances might appear only at certain stages of the life cycle. The
      heterogamous species C. allensworthii demonstrates chemotaxis of male gametes
      towards pheromones excreted by female gametes. In C. reinhardtii chemotaxis
      towards tryptone occurs only in gametes, whereas chemotaxis towards ammonium, on
      the contrary, only in vegetative cells. Chemotaxis to different chemical stimuli
      might involve different mechanisms of reception and signal transduction,
      elucidation of which has only recently begun. Indirect evidences show that the
      cells likely respond to tryptone with changes in the membrane electrical
      conductance. The recently completed project of sequencing the whole nuclear
      genome of C. reinhardtii provides the basis for future identification of
      molecular elements of the chemosensory cascade in this alga.

PMID- 16097935
TI  - Short-term regulation of the alpha-ketoglutarate dehydrogenase complex by energy
      linked and some other effectors.
AB  - The question of regulation of alpha-ketoglutarate dehydrogenase complex (KGDHC)
      has been considered in the biochemical literature very rarely. Moreover, such
      information is not usually accurate, especially in biochemical textbooks. From
      the mini-review of research works published during the last 25 years, the
      following basic view is clear: a) animal KGDHC is very sensitive to ADP, P(i),
      and Ca2+; b) these positive effectors increase manifold the affinity of KGDHC to
      alpha-ketoglutarate; c) KGDHC is inhibited by ATP, NADH, and succinyl-CoA; d) the
      ATP effect is realized in several ways, probably mainly via opposition versus ADP
      activation; e) NADH, besides inhibiting dihydrolipoamide dehydrogenase component
      competitively versus NAD+, decreases the affinity of alpha-ketoglutarate
      dehydrogenase to substrate and inactivates it; f) thioredoxin protects KGDHC from
      self-inactivation during catalysis; g) bacterial and plant KGDHC is activated by
      AMP instead of ADP. These main effects form the basis of short-term regulation of
      KGDHC.

PMID- 16097936
TI  - DNA methyltransferases and structural-functional specificity of eukaryotic DNA
      modification.
AB  - Properties of the main families of mammalian, plant, and fungal DNA
      methyltransferases are considered. Structural-functional specificity of
      eukaryotic genome sequences methylated by DNA methyltransferases is
      characterized. The total methylation of cytosine in DNA sequences is described,
      as well as its relation with RNA interference. Mechanisms of regulation of
      expression and modulation of DNA methyltransferase activity in the eukaryotic
      cell are discussed.

PMID- 16097937
TI  - DNA demethylation and carcinogenesis.
AB  - DNA methylation plays an important role in the establishment and maintenance of
      the program of gene expression. Tumor cells are characterized by a paradoxical
      alteration of DNA methylation pattern: global DNA demethylation and local
      hypermethylation of certain genes. Hypermethylation and inactivation of tumor
      suppressor genes are well documented in tumors. The role of global genome
      demethylation in carcinogenesis is less studied. New data provide evidence for
      independence of DNA hypo- and hypermethylation processes in tumor cells. These
      processes alter expression of genes that have different functions in malignant
      transformation. Recent studies have demonstrated that global decrease in the
      level of DNA methylation is related to hypomethylation of repeated sequences,
      increase in genetic instability, hypomethylation and activation of certain genes
      that favor tumor growth, and increase in their metastatic and invasive potential.
      The recent data on the role of DNA demethylation in carcinogenesis are discussed
      in this review. The understanding of relationships between hypo- and
      hypermethylation in tumor cells is extremely important due to reversibility of
      DNA methylation and attempts to utilize for anti-tumor therapy the drugs that
      modify DNA methylation pattern.

PMID- 16097938
TI  - Identification of beta-lactamase inhibitory peptide using yeast two-hybrid
      system.
AB  - Random oligonucleotide fragments were designed and amplified by PCR and fused
      with the activating domain of pGAD424 to construct a random peptide library. The
      DNA fragment encoding beta-lactamase was fused with the binding domain of
      pGBT9(+2). Subsequently, using yeast two-hybrid system we found two positive
      clones encoding peptides P1 and P2 that have the ability to bind beta-lactamase
      in vivo. The genes encoding P1 and P2 were cloned into pGEX-4T-1. GST-peptide
      fusion proteins were expressed in Escherichia coli and isolated by glutathione
      Sepharose 4B affinity chromatography. Finally, P1 and P2 were cleaved from the
      fusion protein with thrombin and purified by ultrafiltration. Inhibition assay of
      peptides with beta-lactamase in vitro indicated that only P1 has the ability to
      inhibit beta-lactamase.

PMID- 16097939
TI  - Oxidative processes induced by tert-butyl hydroperoxide in human red blood cells:
      chemiluminescence studies.
AB  - The erythrocyte is a good model for investigation of the mechanisms of cell
      damage induced by oxidizing agents. Oxidative damage to cell components and
      cellular metabolism results in impaired rheological properties of circulating red
      blood cells and is involved in the development of some pathologies. The aim of
      the present study was to elucidate further the oxidative processes induced by
      tert-butyl hydroperoxide (tBOOH) in erythrocytes, identify cellular targets
      damaged by the oxidant, as well as estimate the energy and stoichiometry of the
      reactions that occur. The generation of free radicals in the cell was registered
      using the chemiluminescence technique. The products of oxyhemoglobin (oxyHb)
      oxidation, changes in intracellular glutathione (GSH) pool, and accumulation of
      the stable products of membrane lipid peroxidation were concurrently measured.
      The oxidative processes induced by tBOOH in red blood cells can be described as
      follows: 1) rapid GSH oxidation (30-60 sec) by glutathione peroxidase; 2)
      formation of radicals in the reaction between tBOOH and cellular Hb, which are
      then immediately consumed in lipid peroxidation reactions; 3) generation of
      chemiluminescence by the radicals formed. Several stages of the oxidative
      processes can be revealed. The order of the chemiluminescence reaction (n) with
      respect to oxidant was estimated to be equal to 2.5 at oxidant concentrations
      less than 0.5 mM and equal to 1.0 at higher oxidant concentrations. The order of
      the reaction of membrane lipid peroxidation was found to be n = 2.2 at 0.25-0.6
      mM tBOOH and n = 0.5 at higher oxidant concentrations. The apparent activation
      energy of membrane lipid peroxidation was 55.8 +/- 6.4 kJ/mol, and that of oxyHb
      oxidation was 108 +/- 16 kJ/mol. It is shown that the interaction of tBOOH and
      HOCl in erythrocytes is accompanied by changes in both the total number of
      radicals generated in the cell and the time corresponding to the maximal rate of
      radical generation.

PMID- 16097940
TI  - Effect of transketolase substrates on holoenzyme reconstitution and stability.
AB  - The influence of transketolase substrates on the interaction of apotransketolase
      with its coenzyme thiamine diphosphate (TDP) and on the stability of the
      reconstituted holoenzyme was studied. Donor substrates increased the affinity of
      the coenzyme for transketolase, whereas acceptor substrate did not. In the
      presence of magnesium ions, the active centers of transketolase initially
      identical in TDP binding lose their equivalence in the presence of donor
      substrates. The stability of transketolase depended on the cation type used
      during its reconstitution--the holoenzyme reconstituted in the presence of
      calcium ions was more stable than the holoenzyme produced in the presence of
      magnesium ions. In the presence of donor substrate, the holoenzyme stability
      increased without depending on the cation used during the reconstitution. Donor
      substrate did not influence the interaction of apotransketolase with the inactive
      analog of the coenzyme N3'-pyridyl thiamine diphosphate and did not stabilize the
      transketolase complex with this analog. The findings suggest that the effect of
      the substrate on the interaction of the coenzyme with apotransketolase and on
      stability of the reconstituted holoenzyme is caused by generation of 2
      (alpha,beta-dihydroxyethyl)thiamine diphosphate (an intermediate product of the
      transketolase reaction), which has higher affinity for apotransketolase than TDP.

PMID- 16097941
TI  - Recombinant human ribosomal protein S16: expression, purification, refolding, and
      structural stability.
AB  - The cDNA of human ribosomal protein S16 was cloned into the expression vector pET
      15b. Large-scale production of the recombinant protein was carried out in E. coli
      cells and highly purified protein was isolated. A method for refolding the
      protein from inclusion bodies was optimized. The secondary structure content of
      the refolded protein was analyzed by CD spectroscopy. It was found that 21 +/- 4%
      of the amino acid sequence of the protein forms alpha-helices and 24 +/- 3% is in
      beta-strands. The protein structure stability was studied at various pH values
      and urea concentrations. The protein is quickly denatured at pH above 8.0,
      whereas increasing of urea concentration causes slow unfolding of the protein.

PMID- 16097942
TI  - Ability of different glycoprotein IIb-IIIa ligands to support platelet
      aggregation induced by activating antibody CRC54.
AB  - The ability of different ligands of glycoprotein (GP) IIb-IIIa (alphaIIb/beta3
      integrin) to support platelet aggregation stimulated by activating anti-GP IIb
      IIIa monoclonal antibody (monoAB) CRC54 has been investigated. Antibody CRC54
      stimulated aggregation of washed platelets not only in the presence of
      fibrinogen, the main GP IIb-IIIa ligand, but also in the presence of von
      Willebrand factor (vWF). Unlike these ligands, fibronectin failed to support
      CRC54-induced aggregation. Fibrinogen and vWF dependent platelet aggregation was
      completely suppressed by GP IIb-IIIa antagonists--preparations Monafram (F(ab')2
      fragments of monoAB that blocked GP IIb-IIIa receptor activity) and aggrastat
      (RGD-like peptidomimetic). However, aggregation stimulated in the presence of vWF
      was also completely inhibited by monoAB AK2 directed against GP Ib and capable of
      blocking its binding with vWF. CRC54-induced aggregation of platelets from
      patient with GP Ib deficiency in the presence of vWF was significantly lower than
      aggregation of platelets from normal donors and was not inhibited by anti-GP Ib
      antibody but still blocked by GP IIb-IIIa antagonist Monafram. Monafram also
      suppressed CRC54-stimulated platelet adhesion to plastic-adsorbed fibrinogen,
      vWF, and fibronectin. Unlike CRC54-induced platelet aggregation supported by
      fluid phase vWF, CRC54-induced adhesion to adsorbed vWF was not affected by anti
      GP Ib antibody. Aggregation induced by CRC54 in the presence of fibrinogen and
      vWF was only partially suppressed by prostaglandin E1, an inhibitor of platelet
      activation, and was associated with serotonin release from platelet granules only
      when Ca2+ concentration was decreased from 1 mM (physiological level) to 0.1 mM.
      The data indicate that vWF supports CRC54-induced platelet aggregation via
      interaction with two receptors--GP IIb-IIIa and GP Ib. Aggregation induced by
      CRC54 in the presence of vWF or fibrinogen is only partially dependent on
      platelet activation and is accompanied with granule secretion only at low Ca2+
      concentrations.

PMID- 16097943
TI  - Conformational stability and hemolytic activity of actinoporin RTX-SII from the
      sea anemone Radianthus macrodactylus.
AB  - The spatial organization of actinoporin RTX-SII from the sea anemone Radianthus
      macrodactylus on the level of tertiary and secondary structures was studied by UV
      and CD spectroscopy and intrinsic protein fluorescence. The specific and molar
      extinction coefficients of RTX-SII were determined. The percentages of canonical
      secondary structures of actinoporin were calculated. The tertiary structure of
      the polypeptide is well developed and its secondary structure is highly ordered
      and contains about 50% antiparallel folded beta-sheets. The irreversible thermal
      denaturation of RTX-SII was studied by CD spectroscopy; a conformational
      transition occurs at 53 degrees C. Above this temperature irreversible
      conformational changes are observed in the secondary and tertiary structures.
      This is accompanied by redistribution of the content of regular and distorted
      forms of beta-sheet and also by increase in the content of an unordered form. It
      is suggested that an intermediate is formed in the process of thermal
      denaturation. Acid-base titration of RTX-SII results in irreversible
      conformational changes at pH below 2.0 and above 12.0. As shown by intrinsic
      protein fluorescence, tyrosine residues of RTX-SII make a fundamental
      contribution to emission, and the total fluorescence depends more on temperature
      and ionic strength of the solution than tryptophan fluorescence. The data on
      conformational stability of actinoporin are correlated with data on its hemolytic
      activity. Activity of RTX-SII significantly decreases at increased temperature
      and slightly decreases at low pH. Hemolytic activity drastically increases at
      high pH. Increase in the actinoporin activity at pH above 10 seems to be caused
      by ionization of the molecule.

PMID- 16097944
TI  - Characterization of molybdenum-free nitrate reductase from haloalkalophilic
      bacterium Halomonas sp. strain AGJ 1-3.
AB  - Nitrate reductase from the haloalkalophilic denitrifying bacterium Halomonas sp.
      strain AGJ 1-3 was isolated and purified to homogeneity. The isolated enzyme
      belongs to a novel family of molybdenum-free nitrate reductases. It presents as a
      130-140 kD monomeric protein with specific activity of 250 micromol/min per mg
      protein. The enzyme reduces not only nitrate, but also other anions, thus showing
      polyoxoanion reductase activity. Enzyme activity was maximal at pH 7.0 and 70-80
      degrees C.

PMID- 16097945
TI  - Use of Ramachandran plot for increasing thermal stability of bacterial formate
      dehydrogenase.
AB  - From analysis of Ramachandran plot for NAD+-dependent formate dehydrogenase from
      the methylotrophic bacterium Pseudomonas sp. 101 (FDH, EC 1.2.1.2), five amino
      acid residues with non-optimal values phi and psi have been located in beta- and
      pi-turns of the FDH polypeptide chain, e.g., Asn136, Ala191, Tyr144, Asn234, and
      His263. To clarify their role in the enzyme stability, the residues were replaced
      with Gly by means of site-directed mutagenesis. The His263Gly mutation caused FDH
      destabilization and a 1.3-fold increase in the monomolecular inactivation rate
      constant. The replacements Ala191Gly and Asn234Gly had no significant effect on
      the stability. The mutations Asn136Gly and Tyr144Gly resulted in higher thermal
      stability and decreased the inactivation rate by 1.2- and 1.4-fold, respectively.
      The stabilizing effect of the Tyr144Gly mutation was shown to be additive when
      introduced into the previously obtained mutant FDH with enhanced thermal
      stability.

PMID- 16097946
TI  - Isolation, purification, and characterization of nitrate reductase from a salt
      tolerant Rhodotorula glutinis yeast strain grown in the presence of tungsten.
AB  - The salt-tolerant Rhodotorula glutinis yeast strain grew in medium containing
      nitrate, 1 mM tungsten, and trace amounts of molybdenum (as impurities from the
      reagents used). Isolation of electrophoretically homogenous preparation of
      nitrate reductase from the Rh. glutinis cells grown under these growth conditions
      is described. The isolated nitrate reductase is a molybdenum-containing homodimer
      with molecular mass of 130 kD, containing 0.177 mol of Mo per mol of the enzyme.
      The activity of the enzyme is maximal at pH 7.0 and 35-45 degrees C and is
      inhibited by low concentrations of azide and cyanide. The enzyme is almost
      insensitive to 1 mM tungsten.

PMID- 16097947
TI  - Possible mechanism for formation and regulation of the palmitate-induced
      cyclosporin A-insensitive mitochondrial pore.
AB  - The mechanism of the palmitate-induced opening of the mitochondrial Ca2+
      dependent cyclosporin A (CsA)-insensitive pore was studied, as well as the
      influence on this process of well-known modulators of the CsA-sensitive Ca2+
      dependent pore. Palmitic acid, which can bind Ca2+ with high affinity, induced
      the cyclosporin A-insensitive swelling of mitochondria, whereas palmitoleic and 2
      bromopalmitic acids, which have no such affinity for Ca2+, failed to induce the
      pore opening. The palmitate-induced Ca2+-dependent swelling of mitochondria was
      not affected by a well-known inhibitor of the CsA-sensitive pore (ADP) and an
      activator of this pore (inorganic phosphate, P(i)). However, this swelling was
      inhibited by physiological concentrations of ATP ([I]50 = 1.3 mM), but 100 microM
      ATP increased by 30% the rate of mitochondria swelling if Ca2+ had been added
      earlier. The effects of ATP (inhibition and activation) manifested themselves
      from different sides of the inner mitochondrial membrane. Mg2+ inhibited the
      palmitate-induced Ca2+-dependent swelling of mitochondria with [I]50 = 0.8 mM. It
      is concluded that palmitic acid induces the opening of the CsA-insensitive pore
      due to its ability for complexing with Ca2+. A possible mechanism of the pore
      formation and the influence of some modulators on this process are discussed.

PMID- 16097948
TI  - Spectral study of interactions of 4,8,4'-trimethylpsoralen and 4,4'
      dimethylangelicin dyes with DNA.
AB  - Absorption and fluorescence spectra for six new synthetic dyes of 4,8,4'
      trimethylpsoralen and 4,4'-dimethylangelicin derivatives containing various
      terminal substituents at 5'-position have been investigated in different
      environments using a wide range of the DNA/ligand concentrations. Various
      spectral and binding characteristics of the DNA-ligand systems have been
      determined. General principles characterizing mechanisms responsible for changes
      in the fluorescent properties of nucleotide-specific dyes have been proposed;
      they take into consideration chemical structure of the dyes, properties of the
      environment, and degree of sorption on substrate.

PMID- 16097949
TI  - Re-evaluation of receptor-ligand interactions of the human neuropeptide Y
      receptor Y1: a site-directed mutagenesis study.
AB  - Interactions of the human NPY (neuropeptide Y) receptor Y1 with the two
      endogenous agonists NPY and peptide YY and two non-peptide antagonists were
      investigated using site-directed mutagenesis at 17 positions. The present study
      was triggered by contradictions among previously published reports and
      conclusions that seemed inconsistent with sequence comparisons across species and
      receptor subtypes. Our results show that Asp287, at the border between TM
      (transmembrane) region 6 and EL3 (extracellular loop 3) influences peptide
      binding, while two aspartic residues in EL2 do not, in agreement with some
      previous studies but in disagreement with others. A hydrophobic pocket of the Y1
      receptor consisting of Tyr100 (TM2), Phe286 (TM6) and His298 (EL3) has been
      proposed to interact with the amidated C-terminus of NPY, a theory that is
      unsupported by sequence comparisons between Y1, Y2 and Y5. Nevertheless, our
      results confirm that these amino acid residues are critical for peptide binding,
      but probably interact with NPY differently than proposed previously. Studies with
      the Y1-selective antagonist SR120819A identified a new site of interaction at
      Asn116 in TM3. Position Phe173 in TM4 is also important for binding of this
      antagonist. In contrast with previous reports, we found that Phe173 is not
      crucial for the binding of BIBP3226, another selective Y1 receptor antagonist.
      Also, we found that position Thr212 (TM5) is important for binding of both
      antagonists. Our mutagenesis results and our three-dimensional model of the
      receptor based on the high-resolution structure of bovine rhodopsin suggest new
      interactions for agonist as well as antagonist binding to the Y1 receptor.

PMID- 16097950
TI  - Specific conformational changes of plasminogen induced by chloride ions, 6
      aminohexanoic acid and benzamidine, but not the overall openness of plasminogen
      regulate, production of biologically active angiostatins.
AB  - The overall conformation of plasminogen depends upon the presence of anions and
      molecules such as AHA (6-aminohexanoic acid) and BZ (benzamidine). The purpose of
      the present study was to determine the effect of conformation on the initial and
      secondary cleavages of plasminogen to generate active angiostatins. Plasminogen
      was digested with the physiologically relevant neutrophil elastase in one of the
      four Tris/acetate buffers: buffer alone or buffer plus NaCl, AHA or BZ. The
      initial cleavage of Glu1-plasminogen was much slower in the tight NaCl-induced
      alpha-conformation, fastest in the intermediate BZ-induced beta-conformation and
      intermediate both in the control and in the AHA-induced open gamma-conformation.
      Although the buffer system determined the relative amounts of the initial
      cleavage products, the same four cleavage sites were utilized under all
      conditions. A fifth major initial cleavage within the protease domain was
      observed in the presence of BZ. N-terminal peptide cleavage required for
      angiostatin formation occurred as either the initial or the secondary cleavage.
      Angiostatins were generated fastest in the presence of BZ and slowest in the
      presence of NaCl. Both the initial and secondary cleavages were affected by the
      modifying agents, indicating that they influence the conformation of both Glu
      plasminogen and the initial cleavage products. The angiostatins produced under
      the different conditions inhibited proliferation of human umbilical-vein
      endothelial cells. These results suggest that plasminogen conversion into active
      angiostatins is dependent more on the specific conformation changes induced by
      the various modifying reagents rather than on the overall openness of the
      molecule.

PMID- 16097951
TI  - Induction of apoptosis by lipophilic activators of CTP:phosphocholine
      cytidylyltransferase alpha (CCTalpha).
AB  - Farnesol (FOH) inhibits the CDP-choline pathway for PtdCho (phosphatidylcholine)
      synthesis, an activity that is involved in subsequent induction of apoptosis.
      Interestingly, the rate-limiting enzyme in this pathway, CCTalpha
      (CTP:phosphocholine cytidylyltransferase alpha), is rapidly activated, cleaved by
      caspases and exported from the nucleus during FOH-induced apoptosis. The purpose
      of the present study was to determine how CCTalpha activity and PtdCho synthesis
      contributed to induction of apoptosis by FOH and oleyl alcohol. Contrary to
      previous reports, we show that the initial effect of FOH and oleyl alcohol was a
      rapid (10-30 min) and transient activation of PtdCho synthesis. During this
      period, the mass of DAG (diacylglycerol) decreased by 40%, indicating that
      subsequent CDP-choline accumulation and inhibition of PtdCho synthesis could be
      due to substrate depletion. At later time points (>1 h), FOH and oleyl alcohol
      promoted caspase cleavage and nuclear export of CCTalpha, which was prevented by
      treatment with oleate or DiC8 (dioctanoylglycerol). Protection from FOH-induced
      apoptosis required CCTalpha activity and PtdCho synthesis since (i) DiC8 and
      oleate restored PtdCho synthesis, but not endogenous DAG levels, and (ii) partial
      resistance was conferred by stable overexpression of CCTalpha and increased
      PtdCho synthesis in CCTalpha-deficient MT58 cells. These results show that DAG
      depletion by FOH or oleyl alcohol could be involved in inhibition of PtdCho
      synthesis. However, decreased DAG was not sufficient to induce apoptosis provided
      nuclear CCTalpha and PtdCho syntheses were sustained.

PMID- 16097952
TI  - Role of MKK3 and p38 MAPK in cytokine-induced death of insulin-producing cells.
AB  - The aim of the present investigation was to elucidate further the importance of
      p38 MAPK (mitogen-activated protein kinase) in nitric oxide- and cytokine-induced
      beta-cell death. For this purpose, isolated human islets were treated with d
      siRNA (diced small interfering RNA) and then exposed to the nitric oxide donor
      DETA/NONOate [2,2'-(hydroxynitrosohydrazono)bis-ethanamine]. We observed that
      cells treated with p38alpha-specific d-siRNA, but not with d-siRNA targeting GL3
      (a firefly luciferase siRNA plasmid) or PKCdelta (protein kinase Cdelta), were
      protected against nitric oxide-induced death. This was paralleled by an increased
      level of Bcl-XL (B-cell leukaemia/lymphoma-X long). For an in-depth study of the
      mechanisms of p38 activation, MKK3 (MAPK kinase 3), MKK6 and their dominant
      negative mutants were overexpressed in insulin-producing RIN-5AH cells. In
      transient transfections, MKK3 overexpression resulted in increased p38
      phosphorylation, whereas in stable MKK3-overexpressing RIN-5AH clones, the
      protein levels of p38 and JNK (c-Jun N-terminal kinase) were decreased, resulting
      in unaffected phospho-p38 levels. In addition, a long-term MKK3 overexpression
      did not affect cell death rates in response to the cytokines interleukin-1beta
      and interferon-gamma, whereas a short-term MKK3 expression resulted in increased
      cytokine-induced RIN-5AH cell death. The MKK3-potentiating effect on cytokine
      induced cell death was abolished by a nitric oxide synthase inhibitor, and MKK3
      stimulated p38 phosphorylation was enhanced by inhibitors of phosphatases.
      Finally, as the dominant-negative mutant of MKK3 did not affect cytokine-induced
      p38 phosphorylation, and as wild-type MKK3 did not influence p38
      autophosphorylation, it may be that p38 is activated by MKK3/6-independent
      pathways in response to cytokines and nitric oxide. In addition, it is likely
      that a long-term increase in p38 activity is counteracted by both a decreased
      expression of the p38, JNK and p42 genes as well as an increased
      dephosphorylation of p38.

PMID- 16097953
TI  - Biotinylation of glycan chains in beta2 glycoprotein I induces dimerization of
      the molecule and its detection by the human autoimmune anti-cardiolipin antibody
      EY2C9.
AB  - Binding of beta2GPI (beta2 glycoprotein I), a human plasma protein, to AnPLs
      (anionic phospholipids) plays a key role in the formation of antiphospholipid
      antibodies involved in autoimmune diseases like antiphospholipid syndrome or
      systemic lupus erythematosus. We recently showed that binding of beta2GPI to
      AnPLs was enhanced by biotinylation of its glycan chains with biotin-hydrazide.
      In the present study, we investigated why this chemical modification of beta2GPI
      increased both its affinity for AnPLs and its recognition by anti-cardiolipin
      antibodies. Electrophoretic analysis showed that: (i) high molecular mass
      beta2GPI (dimers and other oligomers) covalently coupled by imine bonds, were
      present in variable amounts in oxidized beta2GPI and in beta2GPI-bh (beta2GPI
      biotin-hydrazide), but were absent in native beta2GPI; (ii) binding of beta2GPI
      bh to phosphatidylserine-coated microtitre plates generated high molecular mass
      polymers in a time-dependent manner. Native beta2GPI did not polymerize in these
      conditions. These polymers did not bind more strongly to AnPLs than the monomer
      beta2GPI. However, in solution at 1 microM beta2GPI-bh essentially appeared as a
      dimer as revealed by light-scattering analysis. SPR (surface plasmon resonance)
      analysis showed that the increased affinity of beta2GPI-bh for AnPL monolayers
      was due to a lower dissociation rate constant compared with native beta2GPI.
      Finally, the monoclonal human aCL (auto-immune anti-cardiolipin antibody) EY2C9
      bound to beta2GPI-bh but did not bind to monomeric native and oxidized beta2GPI.
      It is likely that the dimeric quaternary structure of beta2GPI-bh is in fact
      responsible for the appearance of the epitopes targeted by the EY2C9 antibody.

PMID- 16097954
TI  - Maternal valproate dosage and foetal malformations.
AB  - OBJECTIVE- To study the possible dose dependence of the foetal malformation rate
      after exposure to sodium valproate in pregnancy METHODS- Analysis of records of
      all foetuses in the Australian Registry of Antiepileptic Drugs in Pregnancy
      exposed to valproate, to carbamazepine, lamotrigine or phenytoin in the absence
      of valproate, and to no antiepileptic drugs. RESULTS- The foetal malformation
      rate was higher (P<0.05) in the 110 foetuses exposed to valproate alone (17.1%),
      and in the 165 exposed to valproate, whether alone or together with the other
      antiepileptic drugs (15.2%), than in the 297 exposed to the other drugs without
      valproate (2.4%). It was also higher (P<0.10) than in the 40 not exposed to
      antiepileptic drugs (2.5%). Unlike the situation for the other drugs, the
      malformation rate in those exposed to valproate increased with increasing
      maternal drug dosage (P<0.05). The rate was not altered by simultaneous exposure
      to the other drugs. Valproate doses exceeding 1400 mg per day seemed to be
      associated with a more steeply increasing malformation rate than at lower doses
      and with a different pattern of foetal malformations. CONCLUSIONS- Foetal
      exposure to valproate during pregnancy is associated with particularly high, and
      dose-dependent risks of malformation compared with other antiepileptic drugs, and
      may possibly involve different teratogenetic mechanisms.

PMID- 16097955
TI  - Experience with topiramate monotherapy in elderly patients with recent-onset
      epilepsy.
AB  - OBJECTIVES: To evaluate the effect of topiramate in elderly patients with onset
      of epilepsy after the age of 60, treatment-naive or non-responding to an initial
      antiepileptic drug. METHODS: Analysis of patients with epilepsy diagnosed in the
      preceding 5 years, aged>/=65 years (n=43), enrolled in a larger open-label trial
      (n=692). After titration to topiramate 100 mg/day over 4 weeks, the dose was
      adjusted according to individual response (maximum 400 mg/day). Patients were
      followed up for at least 7 months. RESULTS: After 7 months, 79% of patients
      remained in the study. Seizure frequency decreased significantly vs baseline
      (P<0.001); >/=50% reduction in seizure frequency was achieved in 87% of patients,
      64% remained seizure-free. Both previously treated and naive patients responded.
      Fourteen per cent dropped out because of insufficient tolerability. No unexpected
      or unusual adverse events were observed. CONCLUSIONS: The results indicate that
      elderly patients respond well to topiramate monotherapy. The high patient
      retention rate reflects a favourable tolerability profile in this population.

PMID- 16097956
TI  - Parenchymal lesions in pharmacoresistant temporal lobe epilepsy: dual and
      multiple pathology.
AB  - OBJECTIVES: Dual pathology is reported in 5-30% of temporal lobe resections
      performed in pharmacoresistant epilepsy. Dual pathology may be of importance for
      surgical planning and also for the understanding of the pathogenesis of epilepsy.
      We describe the frequency of dual or multiple pathology, i.e. more than one
      histopathological diagnosis, in adults with temporal lobe resections. MATERIAL
      AND METHODS: Surgical specimens from 33 consecutive patients with resections
      including mesial as well as neocortical temporal structures were reviewed. All
      histopathological findings were recorded. Post-mortem specimens from 11 control
      subjects were also reviewed. RESULTS: Dual or multiple pathology was found in
      almost half of the epilepsy patients (48%). Hippocampal sclerosis was found in 25
      patients (76%), malformations of cortical development in 15 (46%), of which 12
      (36%) were microdysgenesis, and low-grade tumours in seven (21%). Apart from mild
      gliosis, there were no histopathological changes in the control specimens.
      CONCLUSION: Dual or multiple pathology was a common finding in this group of
      adults with temporal lobe resections. In order to increase our understanding of
      how aetiological factors may combine in the development of seizures, we consider
      it relevant and important to report all histopathological findings in epilepsy
      surgery series.

PMID- 16097957
TI  - How does stroke restrict participation in long-term post-stroke survivors?
AB  - OBJECTIVE: To explore the factors determining 'restricted participation' in a
      selected population of long-term post-stroke survivors. MATERIALS AND METHODS:
      Seventy-three consecutive post-stroke inpatients were scored for mood and
      restriction in participation by means of self-administered questionnaires,
      respectively the Hospital Anxiety and Depression Scale (HADS/A; HADS/D) and
      London Handicap Scale (LHS). Neurological impairment and functional disability
      were evaluated with the Unified Neurological Stroke Scale (UNSS) and Functional
      Independence Measure (FIM). RESULTS: Physical independence and occupation were
      the most severely affected domains on the LHS. UNSS, FIM, HADS/A, HADS/D scores
      were significant determinants of restriction in participation at univariate
      analysis performed with each LHS domain. FIM score and emotional status finally
      emerged as the independent determinants of restricted participation for the LHS
      domains most related to body function (mobility, physical independence,
      occupation). Depression was the determinant factor for orientation and social
      integration. CONCLUSION: Functional disability and mood disorders may
      independently contribute to the restricted participation of post-stroke patients.
      Most of the LHS domains remain stable over time.

PMID- 16097958
TI  - The effects of environmental light--dark changes on experimental mild traumatic
      brain injury.
AB  - OBJECTIVES: The aim of this study was to investigate the effects of environmental
      light-dark changes on the outcome of mild traumatic brain injury (MTBI) using an
      experimental rodent model. The functions of endogenous and exogenous melatonin on
      the outcome of injury were also investigated METHODS: Mild traumatic brain injury
      was experimentally induced in 56 male Sprague-Dawley rats using a weight-drop
      device. Animals were divided into four groups of 14 each as follows: (i) sham
      operated (trauma only, normal day-night cycle), (ii) treated with melatonin
      (trauma+melatonin, normal day-night cycle), (iii) darkness-induced (trauma+48 h
      constant dark), and (iv) treated with melatonin and darkness-induced (trauma+48 h
      constant dark+melatonin). Melatonin (50 mg/kg) was administered,
      intraperitoneally, immediately after trauma. EEG recordings were taken at three
      time periods (pretrauma, immediately after trauma, and 48 h after trauma). Motor
      functions were tested pretrauma, 24 and 48 h post-trauma. Serum melatonin levels
      were determined pretrauma and 48 h post-trauma. Tissue samples from right frontal
      area were taken 48 h after trauma for light and electron microscopic
      examinations. CONCLUSION: Following MTBI light deprivation alone and light
      deprivation in combination with exogenously administered melatonin indicated
      significant neuroprotective effects. Although there may be other important
      pathways, darkness-induced elevation in endogenous melatonin secretion appears to
      play an important role in this neuroprotective outcome.

PMID- 16097959
TI  - Specific matrix metalloproteinase expression in focal myositis: an
      immunopathological study.
AB  - OBJECTIVES: The aim of our study was to investigate immunoexpression of matrix
      metalloproteinases MMP2, MMP7 and MMP9 in muscle specimens from patients with
      focal myositis (FM) vs polymyositis (PM) and dermatomyositis. MATERIALS AND
      METHODS: We studied muscle biopsy samples from seven patients affected by FM;
      samples from five patients each with PM and dermatomyositis were studied as
      disease controls. RESULTS: MMP2 immunoreactivity was present in PM and
      dermatomyositis, MMP7 only in PM, and MMP9 in PM, dermatomyositis and FM.
      CONCLUSIONS: Our results confirm that increased MMP9 immunoreactivity in muscle
      fibres is a common feature of all inflammatory myopathies and suggest that MMP2
      and MMP7 cannot be implicated in the inflammatory events of FM.

PMID- 16097960
TI  - Entrapment neuropathy in patients with spastic cerebral palsy.
AB  - OBJECTIVES: We performed nerve conduction and needle electromyographic tests in
      29 patients with spastic cerebral palsy (SCP) and severe limb deformities. Nerve
      conduction abnormalities were detected in 32 of 400 sensory or motor nerves,
      while 11 of 29 patients (37.9%) showed abnormal nerve conduction, indicating one
      or more entrapment neuropathies. Patients with SCP develop severe joint
      contractures and deformities due to spastic muscle tone and limited muscle and
      joint use/flexibility; these contractures and deformities can, in turn, cause
      nerve damage, possibly as a result of the stretching, angulation or compression
      mechanisms in the anatomic fibro-osseous passages, where nerves are particularly
      susceptible.

PMID- 16097961
TI  - Relationship between the frequency of autonomic dysfunction and the severity of
      chronic obstructive pulmonary disease.
AB  - OBJECTIVE: The relationship between the frequency of autonomic dysfunction (AD)
      and the severity of chronic obstructive pulmonary disease (COPD) has not been
      exactly known, despite its importance in the pathogenesis of COPD. Therefore, we
      aimed to evaluate the relationship between the clinical stage severity of the
      disease and the frequency of AD in COPD patients. METHODS: The frequency and type
      of AD were determined according to the clinical severity of 35 stable COPD
      patients. The results were compared between the mild and moderate-severe COPD
      groups. Sympathetic system (SS) was evaluated with sympathetic skin response
      (SSR), QT and QTc intervals (ms) analyses. Parasympathetic system was evaluated
      with the heart rate interval variations (RRIV). RESULTS: For the total group, an
      AD was detected in 20 patients (57%), a parasympathetic dysfunction (PD) in 14
      (40%), a mixed-type dysfunction in five (14%) and a sympathetic dysfunction (SD)
      in only one patient (3%). For the 12 mildly affected patients, there were cases
      of isolated SD in only one patient (8.5%), isolated PD in five (42%) and AD in
      six patients (50%). For the 23 moderate-severe COPD patients, mixed AD was
      detected in five patients (22%), isolated PD in nine (39%) and AD in 14 patients
      (61%). There were no significant differences between the two patient groups,
      neither for isolated parasympathetic and sympathetic, mixed form nor for total AD
      (P>0.05). CONCLUSIONS: The results suggested that PD was dominant in patients
      with COPD. However, the frequencies of autonomic parasympathetic and sympathetic
      dysfunction did not increase significantly with the severity of COPD. The
      severity of hypoxemia and/or airflow limitation may not be the only unique or
      definite reason for AD in COPD, as there was not an exact correlation between the
      presence of AD and the severity of airflow limitation and hypoxemia.

PMID- 16097962
TI  - Endovascular ablation of a temporal lobe epileptogenic focus - a complication of
      Wada testing.
AB  - The authors report on a patient with a long history of medically refractory
      temporal lobe epilepsy. During pre-operative evaluation for anterior temporal
      lobectomy he underwent a Wada test for speech and memory lateralization. During
      the procedure, he suffered a focal cerebral infarct, within the right medial
      temporal lobe, at the site of the epileptic focus. This resulted in the
      resolution of his seizure disorder. The possibility of endovascular management of
      seizure disorders of the temporal lobe should be investigated further as a
      potentially minimal invasive therapeutic option for medically intractable
      epilepsy.

PMID- 16097963
TI  - Favorable longitudinal outcome in a patient with Parry-Romberg syndrome.

PMID- 16097964
TI  - Long time interval between multiple sclerosis onset and occurrence of primary
      Sjogren's syndrome in a woman treated with interferon-beta.
AB  - Primary Sjoren's syndrome with central nervous system involvement can clinically
      mimic multiple sclerosis (MS). However, SS and MS may coexist. We report here a
      case of a 48-year-old woman affected by relapsing-remitting MS, good responder to
      interferon (IFN)-beta 1a, developing sicca complex after 29 years from MS onset.
      At the age of 48, after 5 years successful treatment with i.m. IFN-beta 1a,
      xerophtalmia and xerostomia with dysphagia occurred. Autoantibody screening for
      connective tissue diseases, including anti-ENA, was negative. Schirmer's test
      showed reduced lacrimal gland function and a minor salivary gland biopsy showed
      chronic inflammatory infiltration with fibrosis, acinar atrophy and ductal
      ectasia. According to clinical and pathological findings a diagnosis of SS was
      made. Other cases of connective tissue diseases after IFN-beta treatment have
      been described. However, this is, to our knowledge, the first report on the
      development of primary SS after long time interval from MS onset in a woman
      treated with IFN-beta. Although there are no evidences about a possible role of
      IFN-beta in triggering SS yet, a screening for clinical and laboratory signs of
      SS should be assessed in MS patients during IFN-beta treatment.

PMID- 16097965
TI  - Motor aprosodia due to isolated brainstem stroke in a young woman.
AB  - A 21 year old woman presented with coma and quadriparesis secondary to bilateral
      pontine infarction. Three weeks later motor aprosodia was the most notable
      neurological finding apart from mild asymmetric limb weakness. No other
      supratentorial lesion was noted on initial and subsequent multimodality magnetic
      resonance imaging and magnetic resonance perfusion imaging revealed right
      frontotemporal hypoperfusion. This is the first report of aprosodia with an
      isolated brainstem lesion.

PMID- 16097966
TI  - The diagnosis and management of multiple sclerosis.

PMID- 16097967
TI  - Regarding: 'Mosaicism and seizure onset in ring chromosome 20 syndrome'.

PMID- 16097969
TI  - Response to: 'Cortical tremor or cortical pseudotremor?'.

PMID- 16097970
TI  - Do foreign-born women in Sweden have an increased risk of non-normal childbirth?
AB  - BACKGROUND: In this cross-sectional study, we analyze whether foreign-born women
      in Sweden had more non-normal childbirths than Swedish-born women during 1996
      1998, adjusting for age, parity, level of education, number of antenatal care
      visits, and complications in pregnancy. METHODS: The study includes 215 497
      singleton deliveries (including the first childbirth of each woman during the
      time period) of women aged 18-47 in Sweden during 1996-1998, divided into 12
      subgroups of countries. The risk of non-normal birth was analyzed by means of
      logistic regression. RESULTS: Women from Sub-Saharan Africa, Iran, Asia, and
      Latin America had a higher age-adjusted risk of non-normal childbirth than
      Swedish-born women that remained and even increased for the African and Latin
      American women in the main effect model. Interactions between country of birth
      and antenatal care visits showed that women from Sub-Saharan Africa, Iran, Asia,
      and Latin America had almost 50% higher risk of non-normal birth with > or =13
      antenatal care visits than Swedish-born women. Interactions between country of
      birth and complications in pregnancy showed that women from Turkey, Iran, Asia,
      and Latin America had over 50% higher risk of non-normal birth than the Swedish
      born women. CONCLUSIONS: This study shows an association between being foreign
      born and non-normal childbirth. Questions can be raised whether we are aware of,
      pay sufficient attention to, and allocate sufficient resources for these women at
      higher risk of non-normal birth in maternity care.

PMID- 16097971
TI  - Influence of misoprostol (PGE1) on amniotic fluid and maternal serum
      adrenomedullin levels.
AB  - OBJECTIVE: The purpose of this study was to determine the levels of
      adrenomedullin (AdM) in amniotic fluid (AF) and maternal serum of misoprostol
      (PGE1)-induced pregnant women. MATERIALS AND METHODS: A total of 40 women were
      included in the study: 20 were in active labor and were delivered vaginally and a
      further 20 were not in labor and misoprostol induction was performed. Women who
      were undergoing labor induction received 50 microg of misoprostol, which was
      placed in the posterior fornix of the vagina every 4 hrs until the onset of
      labor. In each patient, maternal plasma and AF samples were collected. Samples of
      AF were collected by transvaginal route at the time of rupture of the membranes.
      The labor was at the same stage in both the groups during the sample collection.
      In all pregnant subjects, maternal blood samples were drawn from the cubital vein
      at the time of AF sampling. Amniotic fluid and serum AdM concentration was
      measured by using reverse-phase high-performance liquid chromatography. RESULTS:
      Misoprostol-induced pregnant women showed significantly higher AdM concentrations
      than control pregnant women in AF (79.48 +/- 6.14 pmol/ml versus 21.28 +/- 0.90
      pmol/ml, P = 0.000) and maternal serum (88.20 +/- 4.34 pmol/ml versus 29.78 +/-
      4.51 pmol/ml, P = 0.000). There was no significant difference between maternal
      serum and AF-AdM concentrations in misoprostol and control subjects. CONCLUSION:
      Increased serum and AF-AdM concentrations may be necessary to initiate cervical
      ripening in misoprostol-induced pregnant women.

PMID- 16097972
TI  - Approximate entropy of fetal heart rate variability as a predictor of fetal
      distress in women at term pregnancy.
AB  - BACKGROUND: The aim of this study is to investigate the relationship between
      approximate entropy (ApEn) of fetal heart rate (FHR) with umbilical blood gas
      parameters and the power spectrum of FHR variability in Chinese and to test
      whether ApEn of FHR variability could be used as a predictor of fetal distress in
      women at term pregnancy. METHODS: Sixty-seven pregnant women with singleton, term
      fetus were recruited for the recording of FHR variability and the data were used
      for the estimate of ApEn. Blood gases after birth were measured through umbilical
      artery. RESULTS: In all 67 neonates, there was some amount of interinfant
      variability in the ApEn values with a mean of 1.139 +/- 0.169. The ApEn values
      were significantly (P < 0.05) correlated with pO(2), SO(2), pCO(2), pH, HCO(3),
      or base excess (BE). The 15 fetuses with low ApEn (ApEn <1.0) had higher risk of
      metabolic acidosis (BE less than -12 mmol/l) than those with high ApEn (ApEn > or
      =1) (likelihood ratio = 12.301, P < 0.001). The powers of FHR variability in all
      frequency ranges (0-0.256 Hz) were lower in the low-ApEn group than those in the
      high-ApEn group. CONCLUSIONS: The ApEn of FHR variability significantly decreased
      during fetal asphyxia, including hypoxia, hypercapnia, and both respiratory and
      metabolic acidosis; low ApEn was linked to decreased power spectrum density in
      all frequency domains. The ApEn values may be used as a predictor of fetal
      distress in women at term pregnancy.

PMID- 16097973
TI  - The use of fetal Doppler cerebroplacental blood flow and amniotic fluid volume
      measurement in the surveillance of postdated pregnancies.
AB  - BACKGROUND: This prospective observational study aims at determining the
      distribution of fetal cerebro-placental Doppler indices and amniotic fluid volume
      in a homogenous group of uncomplicated postdated pregnancies at 41 weeks. The
      correlation with incidence of passage of thick meconium-stained liquor in labor
      was analyzed to decide which parameter would be useful in the surveillance of
      postdated pregnancies. METHODS: The amniotic fluid volume, middle cerebral artery
      pulsatility index, umbilical artery pulsatility index, and cerebroplacental ratio
      were measured and distribution determined in 118 well-dated singleton pregnancies
      admitted for routine induction of labor at 41 weeks. The 10th centile and the
      90th centile in each Doppler parameter and amniotic fluid volume were chosen to
      divide each parameter into three centile groups. The prevalence of thick meconium
      stained liquor in labor in different Doppler and amniotic fluid volume centile
      groups was compared using Chi-square test for trend with P < 0.05 taken as
      statistically significant. RESULTS: The prevalence of thick meconium-stained
      liquor in labor was significantly inversely correlated with the middle cerebral
      artery pulsatility index (P = 0.008), with significant difference across
      different middle cerebral artery pulsatility index centile groups (P = 0.02).
      There was no significant difference in the prevalence of thick meconium-stained
      liquor in labor or oligohydramnios across different umbilical artery pulsatility
      index centile groups. Neither was there significant difference in the prevalence
      of thick meconium-stained liquor in labor and oligohydramnios across different
      cerebroplacental ratio and amniotic fluid volume centile groups. Logistic
      regression using the 10th centile of middle cerebral artery pulsatility index
      confirmed that it was a significant independent predicting factor for risk of
      thick meconium-stained liquor in labor with adjusted odds ratio (95th CI) of 6.14
      (1.6-24.1). CONCLUSION: Middle cerebral artery pulsatility index is better than
      amniotic fluid volume or umbilical artery pulsatility index in predicting the
      risk of thick meconium-stained liquor in labor in uncomplicated postdated
      pregnancy at 41 weeks.

PMID- 16097974
TI  - Placental expression of nitric oxide synthase during HELLP syndrome: the
      correlation with maternal-fetal Doppler velocimetry.
AB  - BACKGROUND: To correlate Doppler waveform of the uterine and umbilical vessels to
      placental nitric oxide synthase (NOS) expression in pregnant women with HELLP
      (hemolysis, elevated liver enzymes, low platelets count) syndrome. METHODS: mRNA
      expression of inducible NOS (iNOS) and endothelial NOS (eNOS) was assessed, after
      cesarean section, in placental samples from 10 women affected by HELLP syndrome
      and 10 controls. Pulsatility indices on Doppler waveform analysis from uterine
      and umbilical arteries were measured. RESULTS: iNOS expression was significantly
      lower in placenta from women with HELLP syndrome than controls. When comparing
      the results with Doppler flow measurements, we found a negative correlation
      between umbilical pulsatility index and eNOS expression (r = -0.91) and a
      positive correlation with iNOS expression (r = 0.86). CONCLUSIONS: The reduced
      iNOS expression in women with HELLP syndrome may indicate the extreme placental
      dysfunction that is unable to compensate for the endothelial derangement and
      related hypertension in spite of trying to improve fetoplacental perfusion and
      the delivery of nutrients to the fetus.

PMID- 16097975
TI  - Differences in aspects of personality and sexuality between perimenopausal women
      making different choices regarding prophylactic oophorectomy at elective
      hysterectomy.
AB  - BACKGROUND: Retrospective studies have indicated differences in sexuality and
      general psychological well-being between women who have undergone hysterectomy
      only and those undergoing hysterectomy and oophorectomy. These differences may be
      the result of dissimilarities in the groups of women who choose the respective
      operation. OBJECTIVE: To compare the preoperative characteristics of women who
      choose to undergo prophylactic oophorectomy with the corresponding
      characteristics of those who choose to retain their ovaries when undergoing
      hysterectomy on benign indication. POPULATION: Perimenopausal women (aged 45-55),
      scheduled for hysterectomy on benign indication, were evaluated within 2 months
      before surgery. A total of 217 women chose hysterectomy only and 106 women chose
      hysterectomy with concomitant prophylactic oophorectomy. METHODS: Socioeconomic
      and health data, personality (Karolinska Scale of Personality), sexuality
      (McCoy's Female Sexuality Questionnaire), well-being (Psychological General Well
      Being index), the prevalence of climacteric symptoms (modified Kupperman's index)
      and the women's attitude to hormone replacement therapy were investigated.
      RESULTS: Women who later underwent prophylactic oophorectomy in addition to
      hysterectomy had higher anxiety-related scores, lower sexual variable scores and
      poorer emotional partner relationships. This group was also characterized by more
      episodes of irregular bleeding, a greater prevalence of climacteric symptoms and
      a more extensive use of hormonal replacement therapy, in comparison with women
      who later underwent hysterectomy only. CONCLUSION: Personality, sexuality and the
      nature and severity of preoperative symptoms in women who chose prophylactic
      oophorectomy differ markedly from the same variables in those who chose to keep
      their ovaries at elective hysterectomy. These differences must be taken into
      consideration when evaluating studies comparing these aspects of quality of life
      after hysterectomy or hysterectomy with concomitant oophorectomy. Furthermore,
      psychosexual aspects such as sexuality and well-being can not be reliably studied
      with a retrospective design in these patient groups.

PMID- 16097976
TI  - Fluorescent in situ hybridization: an effective and less costly technique for
      genetic evaluation of products of conception in pregnancy losses.
AB  - OBJECTIVE: In this study, we applied the fluorescent in situ hybridization (FISH)
      technique and compared the common numerical abnormalities with chromosomes 13,
      16, 18, 21, X, and Y in spontaneous to artificial abortion. This would cover
      about 75% of the common aneuploidy in spontaneous abortion. METHODS: Placentas
      were taken from 59 patients with a first trimester spontaneous abortion and 61
      patients who underwent an elective first trimester pregnancy termination. The
      range of growth was from 5 to 12 gestational weeks. Placentas were processed
      according to direct chorionic villi preparation. Direct dual color FISH was
      performed according to Vysis protocol with the probes for the following
      chromosomes: 13, 16, 18, 21, X, and Y. RESULTS: The aneuploidy rate in
      spontaneous abortion was 55.9% and in artificial abortion 8.2%. There was a
      significant difference between the two groups in the aneuploidy rate (P = 6 x 10(
      9)). CONCLUSION: FISH is a rapid, efficient, and relatively inexpensive tool in
      detecting aneuploidy in placentas from cases of spontaneous abortions. Our rate
      of detected aneuploidy is compatible with other reports in which conventional
      cytogenetics was utilized.

PMID- 16097977
TI  - Values of beta-human chorionic gonadotropin as a risk factor for tubal
      obstruction after tubal pregnancy.
AB  - AIM: The hysterosalpingography (HSG) was evaluated after the clinical treatment
      of tubal pregnancy and the possible risk of tubal obstruction through the
      following parameters: beta-human chorionic gonadotropin (beta-hCG) levels, size
      of the adnexal mass, aspects of the image at ultrasound, and color Doppler.
      METHODS: Eighty patients were submitted to HSG after tubal pregnancy treatment
      from April 1994 to February 2002. Fifty received expectant management and 30 were
      treated with single-dose methotrexate (MTX) (50 mg/m(2) intramuscularly).
      RESULTS: The patency of the ipsilateral tube was 84% and 78% after the MTX and
      expectant treatments, respectively (P > 0.05). After the logistic regression was
      performed, it was observed that levels of beta-hCG >5000 mUI/ml were directly
      related to the tubal obstruction risk, odds ratio = 11.79 (95% CI = 2.27-61.32).
      Other variables were not directly related to the tubal obstruction risk.
      CONCLUSIONS: In this study, the probability of ipsilateral tubal obstruction
      depends on the beta-hCG levels. The increase in beta-hCG levels is followed by an
      enhancement in tubal obstruction risk. Therefore, the beta-hCG may be effective
      for the prognostic of the reproductive future of these patients.

PMID- 16097978
TI  - Anatomical basis for nerve-sparing radical hysterectomy: immunohistochemical
      study of the pelvic autonomic nerves.
AB  - BACKGROUND: Autonomic nerve damage plays a crucial role in the etiology of
      bladder dysfunction, sexual dysfunction, and colorectal motility disorders that
      occur after radical hysterectomy. We investigated the extent and nature of nerve
      damage in conventional and nerve-sparing radical hysterectomy. METHODS:
      Macroscopical disruption of nerves was assessed through anatomical dissection
      after conventional and nerve-sparing surgery on five fixed and one fresh cadaver.
      Immunohistochemical analysis of surgical margins was performed to confirm nerve
      damage using a general nerve marker (S100) and a sympathetic nerve marker (anti
      tyrosine hydroxylase) within sections of biopsies. RESULTS: Macroscopical
      dissection showed that in the conventional procedure, transsection of the
      uterosacral ligaments resulted in disruption of the major part of the hypogastric
      nerve. After nerve-sparing surgery, only the medial branches of the hypogastric
      nerve appeared disrupted. Division of the cardinal ligaments in the conventional
      procedure identified the inferior hypogastric plexus running into the most
      posterior border of the surgical margin. The anterior part of the plexus was
      disrupted. Dissection of the nerves after the nerve-sparing procedure showed that
      this anterior part of the plexus was not involved in the surgical dissection
      line. Dissection of the vesicouterine ligament disrupted only small nerves on the
      medial border of the inferior hypogastric plexus in both techniques.
      Microscopical evaluation of the surgical margins confirmed the macroscopical
      findings. CONCLUSION: Conventional radical hysterectomy results in disruption of
      a substantial part of the pelvic autonomic nerves. The nerve-sparing modification
      leads to macroscopic reduction in nerve disruption which is substantiated by
      microscopical evaluation of surgical margins.

PMID- 16097979
TI  - Impact of hypertensive disorders of pregnancy at term on infant birth weight.
AB  - This study was performed to investigate the impact of hypertensive disorders of
      pregnancy at term on neonatal birth weight. All singleton live births delivered
      between 37 and 42 weeks of gestation complicated by hypertensive disorders over a
      7-year period (n = 362) was compared to 34 783 uncomplicated singleton deliveries
      in the same period. The individualized gestation-related optimal weight (GROW)
      was calculated for each individual case adjusted for the effects of maternal
      booking weight, height, parity, gestation at delivery, and fetal sex. Small-for
      gestational-age (SGA) was defined as a birth weight less than the 10th percentile
      of the GROW. The incidence of SGA babies was significantly higher in subjects
      with preeclampsia and eclampsia than in control subjects (24.6 versus 11.3%; odds
      ratio = 2.55; 95% CI: 1.84, 3.55). Preeclampsia significantly reduced fetal birth
      weight by 130 g or 4.3%. Those with eclampsia on average had a neonatal birth
      weight 349 g or 11.0% below that of the GROW. In contrast, there was no
      significant difference in the incidence of SGA babies or degree of deviation from
      GROW between those with or without gestational hypertension.

PMID- 16097980
TI  - The modified Misgav-Ladach versus the Pfannenstiel-Kerr technique for cesarean
      section: a randomized trial.
AB  - BACKGROUND: Modifications to the classic cesarean section technique described by
      Pfannenstiel and Kerr have been proposed in the last few years. The objective of
      this trial was to compare intraoperative and short-term postoperative outcomes
      between the Pfannenstiel-Kerr and the modified Misgav-Ladach (MML) techniques for
      cesarean section. METHODS: This prospective randomized trial involved 162
      patients undergoing transverse lower uterine segment cesarean section. Patients
      were allocated to one of the two arms: 88 to the MML technique and 74 to the
      Pfannenstiel-Kerr technique. Main outcome measures were defined as the duration
      of surgery, analgesic requirements, and bowel restitution by the second
      postoperative day. Additional outcomes evaluated were febrile morbidity,
      postoperative antibiotic use, postpartum endometritis, and wound complications.
      Student's t, Mann-Whitney, and Chi-square tests were used for statistical
      analysis of the results, and a p < 0.05 was considered as the probability level
      reflecting significant differences. RESULTS: No differences between groups were
      noted in the incidence of analgesic requirements, bowel restitution by the second
      postoperative day, febrile morbidity, antibiotic requirements, endometritis, or
      wound complications. The MML technique took on average 12 min less to complete (p
      = 0.001). CONCLUSION: The MML technique is faster to perform and similar in terms
      of febrile morbidity, time to bowel restitution, or need for postoperative
      medications. It is likely to be more cost-effective.

PMID- 16097981
TI  - Nitric oxide increases endocervical secretion at the ovulatory phase in the
      female.
AB  - BACKGROUND: Uterine cervical mucus is crucial for reproduction, facilitating
      sperm transport and survival in certain mammals. Cholinergic autonomic nervous
      secretory innervation has been established, and modulation of secretion by
      prostaglandins and non-steroidal anti-inflammatory drugs has been postulated. It
      has been suggested that glandular nitric oxide (NO) production is a prerequisite
      for the autonomic cholinergic nervous modulation of cervical, endometrial, and
      the seminal vesicle secretion in the guinea pig. Most secretory genital tract
      cells, female as well as male, seem to display NO synthase activity. METHODS:
      Cervical secretion at ovulation time was studied in 10 women with regular
      menstruation. In an in vivo model with repeated collection of mucus samples
      during four 60-min periods, the amount of mucus was estimated in a control
      experimental series and in an experimental series following sublingual
      administration of the NO donor nitroglycerin. RESULTS: This nitroglycerin
      administration markedly increased cervical secretion, while no changes in
      cervical secretion were seen in the control experimental series. CONCLUSIONS: The
      results suggest that glandular NO production increases cervical secretion. Thus,
      cervical secretion may, apart from hormonal regulation, be influenced by the
      autonomic nervous system, and in addition, NO may be a prerequisite for this
      influence. This in turn may have implications on fertilization and fertility
      regulation.

PMID- 16097982
TI  - Immunohistochemical detection of transforming growth factor-alpha, epidermal
      growth factor, and vascular endothelial growth factor expression in
      hyperstimulated rat ovary.
AB  - OBJECTIVE: The aim of the present study is to figure out the immunohistochemical
      expression of transforming growth factor-alpha (TGF-alpha), epidermal growth
      factor (EGF), and vascular endothelial growth factor (VEGF) in hyperstimulated
      rat ovaries. METHODS: Twenty Wistar-Albino adult female rats (250-300 g) were
      taken into the study. The animals were randomly divided into two groups, each
      containing 10 rats: (i) stimulation group and (ii) control group. In the
      stimulation group, a stimulation regimen was administered to induce follicular
      maturity and ovarian hyperstimulation syndrome (OHSS) at the end using a 30-IU
      follicle-stimulating hormone that was administered subcutaneously for 4
      consecutive days, followed by a 30-IU human chorionic gonadotropin on day 5 to
      induce ovulation. The rats, in the control group, received 0.2 ml of 0.9% NaCl
      for 5 consecutive days to mimic the conditions of the study animals. At the end
      of the treatment period, all rats underwent ovariectomy and the sections of
      ovaries were stained for the TGF-alpha, EGF, and VEGF. RESULTS: The expression of
      TGF-alpha, EGF, and VEGF in the endothelium, the stroma, the granulosa cells, and
      the corpus luteum was found to be significantly higher in the stimulated group,
      compared to that in the control group ( p < 0.05). CONCLUSION: TGF-alpha, EGF,
      and VEGF are found to have increased in the hyperstimulated ovaries and this
      finding seems to be involved in the OHSS pathogenesis.

PMID- 16097983
TI  - Pelvic floor dysfunction after Burch colposuspension--a comprehensive study. Part
      I.
AB  - OBJECTIVE: To evaluate the occurrence of voiding dysfunction and symptoms of
      genital prolapse at long-term follow-up after Burch colposuspension (Bc) in
      relation to the occurrence of the symptoms in an age-matched normal population.
      MATERIALS AND METHODS: A follow-up study of the 190 patients who underwent Bc in
      1980-88 and 305 age-matched control women randomly selected from the general
      population. The participants answered a questionnaire in 1998 with detailed
      questions about the pelvic floor function. Univariate and multivariate analyses
      were performed. RESULTS: The prevalence and frequency of urinary incontinence
      were significantly higher in the patient group compared with those in the control
      group as were urge incontinence, difficulty to start voiding, time needed at the
      toilet for voiding, the need to return to the toilet for emptying the bladder,
      feeling of incomplete emptying of the bladder, and limitation of social life
      because of the leakage. The symptoms of genital prolapse were significantly more
      common in the patient group in spite of a significantly larger proportion of
      genital prolapse surgery in this group. Parity, high body mass index, heavy
      lifting work, chronic pulmonary diseases, hiatus hernias, and hysterectomy were
      significantly more common in the patient group than among the controls.
      CONCLUSIONS: At long-term follow-up, patients exhibit substantial symptoms of
      pelvic floor dysfunction (PFD) concerning voiding dysfunction and symptoms of
      genital prolapse compared with a normal population. This highlights the
      importance and need of treating pelvic floor disorders in a comprehensive way.
      Scientific works with comprehensive studies of PFD are needed.

PMID- 16097984
TI  - Pelvic floor dysfunction after Burch colposuspension--a comprehensive study. Part
      II.
AB  - OBJECTIVE: To evaluate the prevalence of pelvic floor dysfunction (PFD)
      concerning bowel function at long-term follow-up after Burch colposuspension (Bc)
      in relation to the bowel function in an age-matched sample of women in the
      general population. METHODS AND MATERIAL: This is a follow-up study of a cohort
      of 190 patients who underwent Bc in 1980-1988 and 305 age-matched control women
      without urinary anti-incontinence surgery, randomly selected from the general
      population. The participants answered a postal questionnaire with detailed
      questions about the pelvic floor function in 1998. Univariate and multivariate
      analyses were performed. RESULTS: The patients showed considerable signs of bowel
      dysfunction compared with the general population in the following aspects: they
      used the fingers to help emptying the bowel [odds ratio (OR) 3.25 (1.35-7.86)];
      had feeling of incomplete emptying of the bowel [OR 2.29 (1.11-4.73)]; felt no
      warning before passing a motion [OR 3.04 (1.20-7.71)]; had gas incontinence [OR
      1.98 (1.17-3.37); had loose stool incontinence [OR 3.67 (1.43-9.42)]; used
      protection against fecal leakage during daytime [OR 3.22 (1.30-7.95)]; and
      experienced that the bowel function affected the general well-being adversely [OR
      2.15 (1.30-3.56)]. CONCLUSION: The patients who have undergone colposuspension
      for stress urinary incontinence have more symptoms of PFD concerning the bowel
      function than women without urinary anti-incontinence surgery in the general
      population. This affects the general well-being. A comprehensive concept of
      multidisciplinary assessment and treatment of PFD should be encouraged.

PMID- 16097985
TI  - Comparison of three-dimensional hysterosalpingo-contrast-sonography and
      diagnostic laparoscopy with chromopertubation in the assessment of tubal patency
      for the investigation of subfertility.
AB  - BACKGROUND: Two-dimensional hysterosalpingo-contrast-sonography, as a screening
      test for tubal patency for subfertile patients, is limited by the difficulty in
      visualizing the entire Fallopian tube owing to its tortuosity. This major
      disadvantage can be overcome by means of the three-dimensional hysterosalpingo
      contrast-sonography (3D-HyCoSy). The current study compared the efficacy of 3D
      HyCoSy with diagnostic laparoscopy and its feasibility as a screening test for
      tubal patency. METHODS: Twenty-one consecutive patients scheduled to have
      laparoscopy were recruited to undergo the 3D-HyCoSy 2 days before the scheduled
      laparoscopy. Echovist (Schering AG, Berlin, Germany), the ultrasound contrast
      medium, was injected into the uterine cavity via a Foley's catheter. The flow of
      the medium in the Fallopian tube was captured by using three-dimensional power
      Doppler mode and was stored for later analysis. The person analyzing the images,
      the surgeon performing the laparoscopy, and the patients were blinded to the
      patients' identity and the sonography findings. The sonography and the
      laparoscopy findings were compared. The duration for the ultrasound examination,
      pain score, and patient acceptability were assessed. RESULTS: Thirty-four of 42
      (81%) Fallopian tubes were assessed. The sensitivity of 3D-HyCoSy for detecting
      tubal patency was 100% with a specificity of 67%. The positive and negative
      predictive values were 89 and 100%, respectively; the concordance rate was 91%.
      The mean duration (+/- SD) for the 3D-HyCoSy was 13.4 +/- 5.5 min. Fifteen
      patients (71%) regarded the sonography examination as at least acceptable.
      CONCLUSIONS: This study confirmed the feasibility of using 3D-HyCoSy as an
      initial investigation for tubal patency.

PMID- 16097986
TI  - Crash caesarean section--decision-to-delivery interval.

PMID- 16097987
TI  - Right-sided anterior congenital diaphragmatic hernia: prenatal diagnosis with
      magnetic resonance imaging.

PMID- 16097988
TI  - Retroperitoneal lymphangiomyomas presenting as a pelvic mass.

PMID- 16097989
TI  - Two cases of clinically suspected thrombotic thrombocytopenic purpura/hemolytic
      uremic syndrome in the puerperium.

PMID- 16097990
TI  - Puberty menorrhagia secondary to inherited bleeding disorders.

PMID- 16097992
TI  - The anterior abdominal approach for a non-puerperal uterine inversion.

PMID- 16097993
TI  - Review article: drug-induced microscopic colitis - proposal for a scoring system
      and review of the literature.
AB  - The pathophysiology of microscopic colitis is unknown, although it is thought to
      be because of an abnormal immune reaction to luminal antigens in predisposed
      hosts. Specific antigens have not been proved, although various infectious
      triggers and drugs have been proposed. The responsibility of several drugs has
      been questioned, some with strong clinical and/or histological evidence
      suggesting causality. The issue of drug-induced microscopic colitis is important
      because of the burden of this disease. Thus, any case that can be cured by
      withdrawal of a drug must be identified. In this report, we propose a scoring
      system for drug-induced microscopic colitis, adapting existing criteria of drug
      causality, and review the literature using this framework. Based on this review,
      several drugs are identified with intermediate or high likelihood of inducing
      microscopic colitis. Finally, we suggest how to treat individual patients
      suspected of having drug-induced colitis according to the level of evidence for
      that particular drug.

PMID- 16097994
TI  - Upper gastrointestinal haemorrhage associated with low-dose aspirin and anti
      thrombotic drugs - a 6-year analysis and comparison with non-steroidal anti
      inflammatory drugs.
AB  - BACKGROUND: Low-dose aspirin and other anti-thrombotic therapy has been
      increasingly used for vascular protection. AIM: To assess the possibility that
      the incidence of upper gastrointestinal blood loss has changed in subjects using
      these agents in comparison with non-steroidal anti-inflammatory drugs. METHODS:
      We studied the characteristics of all patients with acute upper gastrointestinal
      haemorrhage and attending a single hospital at 3 points over a 6-year period:
      1996 (n = 204), 1999 (n = 224) and in 2002 (n = 252). RESULTS: The incidence of
      haemorrhage in subjects taking low-dose aspirin rose from 15 per 100 000 of the
      population per annum in 1996, to 18 in 1999 and 27 in 2002 (P = 0.004). The
      respective incidence in subjects taking other anti-thrombotic drugs was 4, 8, and
      12 (P < 0.001). No significant change was detected in non-steroidal anti
      inflammatory drug users. However, acute myocardial infarction mortality was 216
      per 100 000 in 1996, 221 in 1999 and fell to 169 in 2002 (P < 0.001).
      CONCLUSIONS: The incidence of upper gastrointestinal haemorrhage in users of low
      dose aspirin and other anti-thrombotic drugs has been steadily rising. This has
      been paralleled by a fall in cardiac mortality.

PMID- 16097995
TI  - Ciprofloxacin suppresses bacterial overgrowth, increases fasting insulin but does
      not correct low acylated ghrelin concentration in non-alcoholic steatohepatitis.
AB  - BACKGROUND: Insulin resistance and oxidative stress induced by products of small
      intestinal bacterial activity are putative factors in the pathogenesis of non
      alcoholic steatohepatitis. Acylated ghrelin is the biologically active form of an
      orexigenic gastric hormone that modifies insulin sensitivity and body
      composition. AIM: To investigate the effect of ciprofloxacin on small intestinal
      bacterial activity, ethanol, ghrelin and insulin in non-alcoholic steatohepatitis
      patients. METHODS: Twelve non-alcoholic steatohepatitis patients and 11 controls
      were studied before and after ciprofloxacin 500 mg b.d. for 5 days. After an
      overnight fast, 75 g glucose was ingested and blood was sampled every 20 min for
      120 min. Acylated and total ghrelin, ethanol and insulin were measured. Small
      intestinal bacterial activity was detected by glucose hydrogen breath test.
      RESULTS: Mean (range) integrated plasma acylated ghrelin which was 102 (21-241)
      and 202 (88-366) pg/mL . 2 h in non-alcoholic steatohepatitis and controls
      respectively (P = 0.015). This difference persisted after correction for body
      mass index and was unaffected by ciprofloxacin treatment. One of six non
      alcoholic steatohepatitis patients positive for small intestinal bacterial
      activity remained positive after ciprofloxacin. In contrast, the one healthy
      control positive for small intestinal bacterial activity remained positive after
      ciprofloxacin (P = 0.025). Ethanol was detected in two subjects in each group,
      becoming immeasurable after ciprofloxacin. In non-alcoholic steatohepatitis
      patients median (range) fasting insulin increased from 113 (10-223) to 152 (32
      396) pmol/L (P < 0.02), after ciprofloxacin. This was accompanied by similar
      changes in insulin resistance. CONCLUSIONS: Small intestinal bacterial activity
      is common in non-alcoholic steatohepatitis. Low acylated ghrelin in non-alcoholic
      steatohepatitis cannot be attributed to small intestinal bacterial activity.
      Changes in fasting insulin and ethanol following ciprofloxacin suggest that these
      parameters may be influenced by small intestinal bacterial activity.

PMID- 16097996
TI  - Impact of precore and core promoter mutations on hepatic histology in patients
      with chronic hepatitis B.
AB  - BACKGROUND: The details of liver histology of patients with precore and core
      promoter mutations are still not clear. AIM: To determine the role of precore and
      core promoter mutations in liver histology in Chinese patients with chronic
      hepatitis B. PATIENTS AND METHODS: Intrahepatic hepatitis B virus DNA (by COBAS
      Amplicor hepatitis B virus Monitor test) and precore and core promoter mutations
      (by a line probe assay) were measured in 54 chronic hepatitis B patients.
      Expression of hepatitis B core antigen, hepatitis B e antigen and hepatitis B
      surface antigen was determined by immunohistological staining. Histological
      activity index was scored according to Knodell's criteria. RESULTS: Compared with
      patients without core promoter mutations, patients with core promoter mutations
      had more severe intrahepatic inflammation and fibrosis, and more cytoplasmic
      expression of hepatitis B core antigen (P = 0.028). No such differences were
      found in patients with and without precore mutations. Logistic regression showed
      that core promoter mutations were independently associated with cytoplasmic
      expression of hepatitis B core antigen (P = 0.026). Intrahepatic hepatitis B
      virus DNA levels correlated with serum hepatitis B virus DNA levels (r = 0.71, P
      < 0.001) and the percentage of hepatitis B core antigen-positive hepatocytes (r =
      0.37, P = 0.047), but had no correlation with serum alanine aminotransferase
      levels nor the degree of inflammation and fibrosis. CONCLUSIONS: Patients with
      core promoter mutations had more severe inflammation and fibrosis, and more
      frequent cytoplasmic expression of hepatitis B core antigen. This suggested that
      core promoter mutations might cause more serious liver disease.

PMID- 16097997
TI  - Risk factors for inflammatory bowel disease in the general population.
AB  - BACKGROUND: The aetiology of inflammatory bowel disease remains largely unknown.
      AIM: We performed a comprehensive assessment of potential risk factors associated
      with the occurrence of inflammatory bowel disease. METHODS: We identified a
      cohort of patients 20-84 years old between 1995 and 1997 registered in the
      General Practitioner Research Database in the UK. A total of 444 incident cases
      of IBD were ascertained and validated with the general practitioner. We performed
      a nested case-control analysis using all cases and a random sample of 10 000
      frequency-matched controls. RESULTS: Incidence rates for ulcerative colitis,
      Crohn's disease, and indeterminate colitis were 11, 8, and 2 cases per 100 000
      person-years, respectively. Among women, we found that long-term users of oral
      contraceptives were at increased risk of developing UC (OR: 2.35; 95% CI: 0.89
      6.22) and CD (OR: 3.15; 95% CI: 1.24-7.99). Similarly, long-term users of HRT had
      an increased risk of CD (OR: 2.60; 95% CI: 1.04-6.49) but not UC. Current smokers
      experienced a reduced risk of UC along with an increased risk of CD. Prior
      appendectomy was associated with a decreased the risk of UC (OR: 0.37; 95% CI:
      0.14-1.00). CONCLUSIONS: Our results support the hypothesis of an increased risk
      of inflammatory bowel disease associated with oral contraceptives use and suggest
      a similar effect of hormone replacement therapy on CD. We also confirmed the
      effects of smoking and appendectomy on inflammatory bowel disease.

PMID- 16097998
TI  - Is coeliac disease screening in risk groups justified? A fourteen-year follow-up
      with special focus on compliance and quality of life.
AB  - BACKGROUND: The benefits of serologic screening for coeliac disease in
      asymptomatic individuals are debatable. AIM: To investigate dietary compliance,
      quality of life and bone mineral density after long-term treatment in coeliac
      disease patients found by screening in risk groups. METHODS: The study comprised
      53 consecutive screen-detected coeliac patients diagnosed 14 years (median) ago.
      Dietary compliance was assessed by interview, 4-day food record and serology.
      Quality of life was evaluated by the Psychological General Well-Being and SF-36
      questionnaires, gastrointestinal symptoms by the Gastrointestinal Symptom Rating
      Scale and bone mineral density by dual-energy x-ray absorptiometry. Comparisons
      were made to 44 symptom-detected-treated coeliac patients, 110 non-coeliac
      subjects and the general population. RESULTS: A total of 96% of screen-detected
      and 93% of symptom-detected coeliac patients adhered to a strict or fairly strict
      gluten-free diet. In screen-detected patients, quality of life and
      gastrointestinal symptoms were similar to those in symptom-detected patients or
      non-coeliac controls and bone mineral density was similar to that in the general
      population. CONCLUSIONS: Long-term dietary compliance in screen-detected patients
      was good. Quality of life and bone mineral density were comparable with those in
      non-coeliac subjects and the general population. Active screening in coeliac
      disease risk groups seems to be reasonable rather than harmful.

PMID- 16097999
TI  - The effect of gastro-oesophageal reflux and omeprazole on key sleep parameters.
AB  - BACKGROUND: The effect of gastro-oesophageal reflux on sleep and sleep quality is
      highly controversial. AIM: To determine the temporal relationship of abnormal
      objective sleep parameters to gastro-oesophageal reflux during acid suppression
      in patients with self diagnosed sleep disorders. METHODS: Polysomnography during
      oesophageal pH monitoring was conducted in 16 subjects with and without gastro
      oesophageal reflux as determined by a standardized questionnaire. Subjects were
      studied before and after omeprazole. RESULTS: All reflux events were followed by
      a sleep arousal or awakening. Nocturnal acid reflux events were not predicted by
      the Carlsson score. Omeprazole reduced acid reflux-associated arousals from 11.6
      +/- 3.8 to 1.5 +/- 0.8 (P < 0.01) and awakenings from 7.7 +/- 1.2 to 3.7 +/- 0.5
      (P < 0.05). Sleep efficiency improved from 70.2% to 81.6% in a small subset of
      subjects with decreased sleep (P < 0.05); rapid eye movement sleep increased from
      55.0 +/- 4.5 to 94.5 +/- 18.9 min (P < 0.05); total sleep time increased from
      294.0 +/- 15.9 to 345.6 +/- 55.6 min (P < 0.05). Apnoea, hypopnoea and hypoxaemia
      were not associated with reflux. CONCLUSIONS: In subjects with gastro-oesophageal
      reflux, sleep arousals and awakenings are closely related to acid reflux events.
      Reflux-related arousals and awakenings are decreased by acid suppression. Acid
      suppression in selected subjects with reflux events and reduced sleep efficiency
      is associated with increased total sleep time, rapid eye movement sleep and sleep
      efficiency.

PMID- 16098000
TI  - Prevalence, clinical spectrum and atypical symptoms of gastro-oesophageal reflux
      in Argentina: a nationwide population-based study.
AB  - BACKGROUND: Population-based data on gastro-oesophageal reflux in Latin America
      are lacking. AIM: To assess gastro-oesophageal reflux symptom prevalence,
      clinical spectrum and association with the atypical symptoms in our country.
      METHODS: Gastro-oesophageal reflux self-report questionnaires validated at Mayo
      Clinic, USA, were submitted to a sample of 1000 residents (aged 18-80 years) from
      17 representative geographical areas of Argentina. The samples were selected and
      stratified according to age, gender, geographical areas and size of town of
      residence provided by the Argentine Bureau of Statistics and Census. RESULTS: The
      overall prevalence of any typical gastro-oesophageal reflux symptom experienced
      in the previous year was 61.2% (95% CI, 57.9-64.6), the prevalence of frequent
      gastro-oesophageal reflux symptoms was 23.0% (95% CI, 20.1-25.9) and the
      prevalence of gastro-oesophageal reflux disease was 11.9% (95% CI, 9.6-14.1).
      Frequent gastro-oesophageal reflux symptoms were associated with dysphagia (OR
      2.12, 95% CI, 1.27-3.54, P < 0.01), globus (OR 2.22, 95% CI, 1.35-3.66, P < 0.01)
      and non-cardiac chest pain (OR 1.55, 95% CI, 1.04-2.31, P < 0.05). CONCLUSIONS:
      In Argentina, typical symptoms of gastro-oesophageal reflux are highly prevalent
      at the national level, and frequent gastro-oesophageal reflux symptoms are
      significantly associated with dysphagia, globus and non-cardiac chest pain.

PMID- 16098001
TI  - Is a long-term ranitidine-based triple therapy against Helicobacter pylori only a
      heritage of the past? A prospective, randomized clinicopharmacological study.
AB  - BACKGROUND: Acid suppression plus two antibiotics is currently considered the
      gold standard anti-Helicobacter pylori treatment, but the effective role of
      gastric antisecretory drugs is still poorly understood. AIMS: To compare a 14-day
      ranitidine-based triple regimen against Helicobacter pylori with one based on
      omeprazole, and to study the influence of antisecretory drugs on metronidazole
      pharmacokinetics in human plasma. METHODS: A total of 150 dyspeptic H. pylori
      infected patients were randomized for ranitidine 300 mg b.d. (RCM group) or
      omeprazole 20 mg b.d. (OCM group) 14-day triple therapy, with clarithromycin 500
      mg b.d. and metronidazole 500 mg b.d. On the eighth day of therapy, metronidazole
      pharmacokinetics was studied in plasma by high-performance liquid chromatography.
      The pharmacokinetic parameters (terminal half-life, area under the curve, peak
      plasma level, peak time) of metronidazole were computed using standard non
      compartmental methods. H. pylori status was monitored before and 4 weeks after
      the end of therapy by histology, serology and rapid urease test. RESULTS: On an
      intention-to-treat basis, eradication rates were 91 and 76% for the RCM and OCM
      groups respectively (P < 0.02). Significantly different pharmacokinetic
      parameters of metronidazole were found between the groups: peak-plasma level (P <
      0.01) and area under the curve (P < 0.02). CONCLUSION: Our results show that the
      RCM regimen was more effective than that based on OCM and that the antisecretory
      drugs affected metronidazole availability, increasing the efficacy of ranitidine
      based regimens.

PMID- 16098002
TI  - Quality of life in acute and maintenance treatment of non-erosive and mild
      erosive gastro-oesophageal reflux disease.
AB  - BACKGROUND: Quality of life has been assessed in a large, multicentre randomized,
      open label study. AIM: To evaluate the economic and clinical consequences of two
      different maintenance treatment modalities, administered to 6017 gastro
      oesophageal reflux disease patients at 451 gastroenterological centres in Italy.
      METHODS: Adult gastro-oesophageal reflux disease patients received, at enrolment,
      an acute treatment of esomeprazole 40 mg/day for 4 weeks and, if successfully
      treated, were randomized into two maintenance treatment strategies: esomeprazole
      20 mg/day or esomeprazole on demand for 6 months. A baseline endoscopy allowed
      the exclusion of grade II-IV oesophagitis according to Savary-Miller's
      classification. Burden of gastro-oesophageal reflux disease was measured at
      baseline by the generic questionnaire Short-Form 36 and by a disease specific
      instrument, quality of life in reflux and dyspepsia (QOLRAD), also administered
      at start and conclusion of maintenance period. Investigators were required to
      collect patient judgement about the degree of satisfaction with treatment effect
      on heartburn, with a 7-point scale. RESULTS: A comparison between Short-Form 36
      scores and the normative source of the Italian general population suggested that
      symptomatic gastro-oesophageal reflux disease patients experience a worse quality
      of life than the general population. At the end of the 4-week treatment with
      esomeprazole 40 mg all (QOLRAD) dimensions showed a statistically significant (P
      < 0.0001) and clinically meaningful improvement. Satisfaction level towards
      treatment was reported high in the total enrolled population after acute
      treatment with esomeprazole 40 mg/day (96.2% satisfied and 64.4% very satisfied).
      A statistically significant difference in (QOLRAD) scores was registered at the
      end of maintenance phase in favour of the continuous regimen, nevertheless the
      size of this difference was very small in all dimensions; similarly, the
      proportion of patients very satisfied was slightly higher in the continuous
      treatment arm (64.5%) than in the on-demand arm (59.7%). CONCLUSIONS: Gastro
      oesophageal reflux disease can significantly impair health-related quality of
      life and esomeprazole therapy allows immediate relief in the acute phase of the
      disease. Quality of life improvement was maintained during the 6-month follow-up
      with a slight difference in term of quality of life in reflux and dyspepsia
      scores and patients' satisfaction in favour of the continuous treatment strategy.

PMID- 16098003
TI  - Validation of the gastrointestinal symptom score for the assessment of symptoms
      in patients with functional dyspepsia.
AB  - AIM: To validate the gastrointestinal symptom score as an outcome measure for
      functional dyspepsia. METHODS: In focus groups, 10 dyspepsia-specific items
      including nausea, sickness, vomiting, bloating, abdominal cramps, early satiety,
      acidic eructation/heartburn, loss of appetite, retrosternal discomfort,
      epigastric pain/upper abdominal pain were identified. Ninety-five patients with
      functional dyspepsia and 56 healthy controls were recruited and responsiveness
      evaluated by analysing gastrointestinal symptom score data from 357 patients from
      previous placebo-controlled trials. Gastrointestinal symptom score response data
      were correlated with the patient's global assessments of efficacy. Convergent
      validity was assessed by correlating the gastrointestinal symptom score with the
      results obtained by the Nepean Dyspepsia Index. RESULTS: Sensitivity: In patients
      and healthy controls gastrointestinal symptom score yielded consistently
      different scores (all P < 0.0001). TEST-RETEST RELIABILITY: Gastrointestinal
      symptom score determined at the two time points were significantly correlated (r
      values ranging from 0.842 to 0.901). CONVERGENCE VALIDITY: Gastrointestinal
      symptom score of both rating groups were significantly correlated with the
      symptom-specific component of the Nepean Dyspepsia Index (r-vales ranging from
      0.666 to 0.764, P < 0.01). RESPONSIVENESS: Responses of gastrointestinal symptom
      score during treatment were different for patients with a global self assessment
      as responders compared with non-responders (all P < 0.0055). CONCLUSION: The
      gastrointestinal symptom score is a valid and reliable instrument to assess
      symptom intensities in patients with functional dyspepsia.

PMID- 16098007
TI  - Sir Archibald Garrod and alkaptonuria -'story of metabolic genetics'.
AB  - Clinical disorders have intrigued the human mind for thousands of years. Many are
      enshrined in history as 'medical curiosities'. This report is a tribute to one of
      the greatest minds of modern genetics and medicine, Sir Archibald Edward Garrod
      (1857--1936), who brought forward the scientific study of inborn errors of
      metabolism. Garrod's concept of 'chemical individuality' with no awareness of
      'genes' more than 100 years ago is an amazing example of futuristic thinking. His
      own words reflect this, 'Owing, as I believe, to their chemical individuality
      different human beings differ widely in their liability to individual maladies,
      and to some extent in the signs and symptoms which they exhibit'. The concept of
      chemical individuality is here to stay. Garrod has also provided insight into a
      number of scientific concepts and modern thinking.

PMID- 16098008
TI  - Clinical and genetic studies in Spanish patients with Usher syndrome type II:
      description of new mutations and evidence for a lack of genotype--phenotype
      correlation.
AB  - Patients with Usher syndrome type II (USH2) show moderate-to-severe hearing loss
      (HL), retinitis pigmentosa and normal vestibular function. The progression of HL
      remains controversial. To evaluate whether a phenotype-genotype correlation
      exists regarding the issue of progression of HL, only USH2 patients with a
      defined genotype were selected. Ophthalmologic, vestibular and audiometric
      examination along with a mutation analysis of the USH2A gene (exons 1--21) was
      performed in twenty-eight Spanish USH2 patients. Ten different pathogenic
      mutations and 17 sequence variants not associated with the disease were found.
      Six of the 10 mutations are novel. Disease alleles were identified in 13 of the
      28 families tested. Eight of these 13 families had a mutation found in both
      alleles. In the other five families, only one mutation was identified. The
      phenotypic data provide evidence for the existence of phenotypic differences
      between patients with the same genotype. These differences were observed at both
      the interfamilial and intrafamilial levels.

PMID- 16098009
TI  - Genotypic heterogeneity and clinical phenotype in triple A syndrome: a review of
      the NIH experience 2000-2005.
AB  - Triple A syndrome (AAAS, OMIM#231550) is an autosomal recessive condition
      characterized by adrenal insufficiency, achalasia, alacrima, neurodegeneration
      and autonomic dysfunction. Mutations in the AAAS gene on chromosome 12q13 have
      been reported in several subjects with AAAS. Over the last 5 years, we have
      evaluated six subjects with the clinical diagnosis of AAAS. Three subjects had
      mutations in the AAAS gene-- including one novel mutation (IVS8+1 G>A)-- and a
      broad spectrum of clinical presentations. However, three subjects with classic
      AAAS did not have mutations in the AAAS gene on both alleles. This finding
      supports the notion of genetic heterogeneity for this disorder, although other
      genetic mechanisms cannot be excluded.

PMID- 16098010
TI  - Psychological functioning in African American women at an increased risk of
      hereditary breast and ovarian cancer.
AB  - Despite attention to psychological issues during genetic counselling and testing
      for hereditary breast and ovarian cancer risk, limited information is available
      on cancer-specific distress among African American women being targeted for
      participation in counselling and testing. Therefore, the purpose of this study is
      to examine cancer-specific distress in African American women at an increased
      risk of hereditary breast and ovarian cancer and to identify factors having
      significant associations with distress in this population. Respondents were 141
      African American women identified for participation in genetic counselling and
      testing for BRCA1/2 mutations. Overall, respondents reported moderate levels of
      cancer-specific distress. Younger age (coefficient=6.0, p=0.001), being
      unemployed (coefficient=-5.0, p=0.01), and having a personal history of cancer
      (coefficient=5.0, p=0.02) had significant associations with intrusion. Younger
      age was also associated significantly with greater avoidance (r=6.0, p=0.02).
      These results suggest that African American women aged 50 and younger, those who
      are unemployed and women with a personal history of breast or ovarian cancer may
      be the most vulnerable to experiencing elevated levels of distress during genetic
      counselling and testing. Greater attention to psychological issues, including
      concerns about cancer and cancer risks, may be needed during genetic counselling
      and testing for BRCA1/2 mutations with these women.

PMID- 16098011
TI  - 'Indirect' BRCA1/2 testing: a useful approach in hereditary breast and ovarian
      cancer families without a living affected relative.
AB  - We report an approach for BRCA1/2 testing whereby genetic testing can be offered
      to families at high risk of hereditary breast and ovarian cancer but where no DNA
      from affected relatives is available. By testing two or more unaffected relatives
      at 50% risk of being heterozygous for a potential BRCA1/2 mutation, there is a
      chance of up to 99% of finding a mutation that would have been detectable in an
      affected individual from the same family. The overall likelihood of identifying a
      mutation is dependent on the family history, and therefore 'indirect' testing
      would be most applicable for families with a very high risk of carrying a BRCA1/2
      mutation. Using this approach also requires balancing issues of testing resource
      limitations, family dynamics and adequate preparation of unaffected persons for a
      positive test, with the advantages of targeting screening and prophylactic
      surgery.

PMID- 16098012
TI  - Novel genomic insertion-- deletion in MLH1: possible mechanistic role for non
      homologous end-joining DNA repair.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited cancer
      syndrome caused by a defect in the mismatch repair pathway. The majority of HNPCC
      mutations have been detected in MLH1 and MSH2. Most reported mutations are
      substitutions, small insertions and deletions, but standard methods of mutation
      analysis do not detect large rearrangements. It is now established that large
      deletions, insertions and rearrangements account for a significant proportion of
      MLH1 and MSH2 mutations. We report an unusual rearrangement resulting in the
      deletion of exons 6, 7 and 8 of MLH1, with the retention of part of intron 6 and
      insertions of two nucleotides each flanking the retained sequence. The 349-bp
      retained sequence is made up of two closely spaced Alu sequences. The mutation
      was initially detected by protein truncation test and cDNA sequencing. Multiplex
      ligation-dependent probe amplification confirmed the deletion of three exons. PCR
      and sequencing were used to characterize the breakpoint. Despite the high density
      of Alu elements in MLH1, there is no homology at the deletion breakpoints or
      insertion junctions in this case to suggest that homologous recombination has
      occurred. We propose a mechanism involving non-homologous end joining to explain
      the occurrence of this complex deletion.

PMID- 16098013
TI  - A novel locus for autosomal dominant hereditary gingival fibromatosis, GINGF3,
      maps to chromosome 2p22.3-p23.3.
AB  - Hereditary gingival fibromatosis (HGF) is a rare, benign disorder characterized
      by slowly progressive fibrous overgrowth of the gingiva. To date, two loci have
      been mapped in familial cases with autosomal dominant non-syndromic HGF: GINGF
      (MIM 135300) on chromosome 2p21-p22 and GINGF2 (MIM 605544) on chromosome 5q13
      q22. Of the two loci, only SOS1 (son of sevenless one, MIM 182530) gene
      underlying GINGF locus has been identified. Ascertainment of a large Chinese
      family has allowed the mapping of a novel locus to 2p22.3-p23.3, GINGF3.
      Haplotype construction and analysis localized the new locus to an 11.4-cM
      interval between markers D2S2221 (telomeric) and D2S1788 (centromeric). The
      maximum two-point limit of detection (LOD) score of 3.45 (theta=0) and multipoint
      LOD score of 5.00 for marker D2S390 strongly supported linkage to this region.
      Thus, this genetic interval is distal to and does not overlap with the previously
      described locus, GINGF, on 2p21-p22.

PMID- 16098014
TI  - Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C
      patients: genotype-phenotype correlations.
AB  - To better characterize Niemann-Pick type C (NPC) in Spain and improve genetic
      counselling, molecular analyses were carried out in 40 unrelated Spanish
      patients. The search identified 70/80 alleles (88%) involving 38 different NPC1
      mutations, 26 of which are described for the first time. No patient with NPC2
      mutations was identified. The novel NPC1 mutations include 14 amino acid
      substitutions [R372W (c.1114C>T), P434L (c.1301C>T), C479Y (c.1436G>A), K576R
      (c.1727G>A), V727F (c.2179G>T), M754K (c.2261T>A), S865L (c.2594C>T), A926T
      (c.2776G>A), D948H (c.2842G>C), V959E (c.2876T>A), T1036K (c.3107C>A), T1066N
      (c.3197C>A), N1156I (c.3467A>T) and F1224L (c.3672C>G)], four stop codon [W260X
      (c.780G>A), S425X (c.1274C>A), C645X (c.1935T>A) and R1059X (c.3175C>T)], two
      donor splice-site mutations [IVS7+1G>A (g.31432G>A) and IVS21+2insG
      (g.51871insG)], one in-frame mutation [N961_F966delinsS (c.2882del16bpins1bp)]
      and five frameshift mutations [V299fsX8 (c.895insT), A558fsX11 (c.1673insG),
      C778fsX10 (c.2334insT), G993fsX3 (c.2973_78delG) and F1221fsX20 (c.3662delT)]. We
      also identified three novel changes [V562V (c.1686G>A), A580A (c.1740C>G) and
      A1187A (c.3561G>T)] in three independent NPC patients and five polymorphisms that
      have been described previously. The combination of these polymorphisms gave rise
      to the establishment of different haplotypes. Linkage disequilibrium was detected
      between mutations C177Y and G993fsX3 and specific haplotypes, suggesting a unique
      origin for these mutations. In contrast, I1061T mutation showed at least two
      different origins. The most prevalent mutations in Spanish patients were I1061T,
      Q775P, C177Y and P1007A (10, 7, 7 and 5% of alleles, respectively). Our data in
      homozygous patients indicate that the Q775P mutation correlates with a severe
      infantile neurological form and the C177Y mutation with a late infantile clinical
      phenotype.

PMID- 16098015
TI  - An exploratory comparison of genetic counselling protocols for HNPCC predictive
      testing.
AB  - Most UK genetics centres offering predictive testing for hereditary non-polyposis
      colorectal cancer (HNPCC) use an extended counselling protocol originally
      developed for Huntington's disease. Shortened counselling may be more appropriate
      in the context of treatable genetic conditions such as HNPCC. Twenty-six high
      risk individuals were randomized to extended genetic counselling (two sessions of
      education and reflection held 1 month apart) or shortened genetic counselling (a
      single educational session) prior to HNPCC testing. Prospective questionnaires,
      interviews and transcripts of counselling sessions were analysed. Participants
      were unsure what to expect prior to genetic counselling and had already decided
      to undergo genetic testing. There was no evidence of psychological harm caused by
      shortened genetic counselling, with a high level of satisfaction with the
      counselling received in both groups. Reflective counselling occurred in both
      groups but was framed in terms of practical action and information. Participants
      expressed differing preferences for the level of information received. This
      exploratory study indicates that shortened genetic counselling may be an
      appropriate means of supporting decisions already made by individuals about HNPCC
      testing. However, participants would benefit from preparatory information to help
      them reflect on issues not previously considered, which can then be explored more
      fully as part of a tailored counselling approach.

PMID- 16098016
TI  - Localization of a novel autosomal recessive non-syndromic hearing impairment
      locus DFNB55 to chromosome 4q12-q13.2.
AB  - Hereditary hearing impairment (HI) is the most genetically heterogeneous trait
      known in humans. So far, 54 autosomal recessive non-syndromic hearing impairment
      (ARNSHI) loci have been mapped, and 21 ARNSHI genes have been identified. Here is
      reported the mapping of a novel ARNSHI locus, DFNB55, to chromosome 4q12-q13.2 in
      a consanguineous Pakistani family. A maximum multipoint LOD score of 3.5 was
      obtained at marker D4S2638. The region of homozygosity and the 3-unit support
      interval are flanked by markers D4S2978 and D4S2367. The region spans 8.2 cm on
      the Rutgers combined linkage-physical map and contains 11.5 Mb. DFNB55 represents
      the third ARNSHI locus mapped to chromosome 4.

PMID- 16098017
TI  - Association of repeat polymorphisms in the estrogen receptors alpha, beta, and
      androgen receptor genes with knee osteoarthritis.
AB  - Genetic factors have been shown to play an important role in the etiology of
      osteoarthritis (OA). To elucidate the possible role of genetic variation in the
      estrogen receptors alpha and beta (ER-alpha, ER-beta) and androgen receptor (AR)
      genes with knee OA, the -1174(TA)(n), c.1092+3607(CA)(n), and c.172(CAG)(n)
      repeat polymorphisms of ER-alpha, ER-beta, and AR genes were studied. A case
      control cohort of 158 patients with idiopathic knee OA and 193 controls were
      used. A significant difference was observed in the frequency distribution of 
      1174(TA)(9-25) and c.1092+3607(CA)(13-27) repeat polymorphisms of the ER-alpha
      and ER-beta genes between OA patients and controls (p<0.005 and p<0.0001,
      respectively). A significantly increased odds ratio (OR) for knee OA was observed
      in individuals having long alleles (LL) genotype for ER-alpha gene and LL and one
      short and one long allele (SL) genotypes for ER-beta gene compared to individuals
      with the short alleles (SS) genotype (95% CI 1.03-3.5; p=0.04 and CI 2.4-8.3 and
      2.5-7.5; p < 0.001, respectively). When ORs were adjusted for various risk
      factors, it was observed that women with LL genotypes for ER-beta and AR genes
      showed significantly increased risk for OA development (p=0.002 and 0.001). An
      association between c.1092+3607(CA)(13-27) and c.172(CAG)(8-34) repeat
      polymorphisms of the ER-beta and AR genes and knee OA was found in individuals of
      Greek descent.

PMID- 16098018
TI  - Copper-replacement treatment for symptomatic Menkes disease: ethical
      considerations.
AB  - We describe a child with classical Menkes disease with a novel ATP7A mutation,
      intractable seizures, severe hypotonia and developmental delay, hypopigmentation
      of the skin and hair, and failure to thrive, who was treated with daily
      subcutaneous copper histidine injections for 2(1/2) years, beginning at 15 months
      of age. He became seizure-free and pigmentation of his skin and hair darkened,
      but he continued to have severe developmental delays. His condition remains
      stable 8 months after stopping treatment. We review the ethical aspects of
      offering copper treatment for Menkes disease infants diagnosed after neurological
      symptoms become manifest. These include (1) the prospect for any benefits, (2)
      the potential risks and discomforts, (3) the parents' wishes with respect to
      treatment, (4) the family's understanding of the treatment's potential futility,
      (5) the family's understanding of the investigational nature of this treatment,
      (6) the potential for treatment to have an adverse impact on unaffected family
      members, (7) whether the ultimate decision regarding treatment should rest with
      health care providers or with the patient's parents, and (8) the duration of
      treatment. The ethical issues encountered in providing possibly futile treatment
      in this difficult disorder seem relevant to other pediatric medical conditions as
      well.

PMID- 16098019
TI  - Syndromic and non-syndromic GLI3 phenotypes.

PMID- 16098024
TI  - Looking beneath the surface--setting the stage for skin ulceration.

PMID- 16098025
TI  - Learning more from microarrays: insights from modules and networks.
AB  - Global gene expression patterns can provide comprehensive molecular portraits of
      biologic diversity and complex disease states, but understanding the physiologic
      meaning and genetic basis of the myriad gene expression changes have been a
      challenge. Several new analytic strategies have now been developed to improve the
      interpretation of microarray data. Because genes work together in groups to carry
      out specific functions, defining the unit of analysis by coherent changes in
      biologically meaningful sets of genes, termed modules, improves our understanding
      of the biological processes underlying the gene expression changes. The gene
      module approach has been used in exploratory discovery of defective oxidative
      phosphorylation in diabetes mellitus and also has allowed definitive hypothesis
      testing on a genomic scale for the relationship between wound healing and cancer
      and for the oncogenic mechanism of cyclin D. To understand the genetic basis of
      global gene expression patterns, computational modeling of regulatory networks
      can highlight key regulators of the gene expression changes, and many of these
      predictions can now be experimentally validated using global chromatin
      immunoprecipitation analysis.

PMID- 16098026
TI  - Stratum corneum defensive functions: an integrated view.
AB  - Most epidermal functions can be considered as protective, or more specifically,
      as defensive in nature. Yet, the term "barrier function" is often used
      synonymously with only one such defensive function, though arguably its most
      important, i.e., permeability barrier homeostasis. Regardless of their relative
      importance, these protective cutaneous functions largely reside in the stratum
      corneum (SC). In this review, I first explore the ways in which the multiple
      defensive functions of the SC are linked and interrelated, either by their shared
      localization or by common biochemical processes; how they are co-regulated in
      response to specific stressors; and how alterations in one defensive function
      impact other protective functions. Then, the structural and biochemical basis for
      these defensive functions is reviewed, including metabolic responses and
      signaling mechanisms of barrier homeostasis. Finally, the clinical consequences
      and therapeutic implications of this integrated perspective are provided.

PMID- 16098027
TI  - Thalidomide enhances the anti-tumor activity of standard chemotherapy in a human
      melanoma xenotransplatation model.
AB  - It has been demonstrated that thalidomide's anti-angiogenic properties result in
      clear anti-tumor activity in a number of human malignancies. We studied
      thalidomide in a human melanoma severe combined immunodeficiency mouse
      xenotransplantation model. Thalidomide as a single agent showed a significant
      tumor reduction of 46% compared with the control group. Thalidomide combined with
      dacarbazine treatment markedly enhanced the anti-tumor effect of chemotherapy and
      showed a significant tumor reduction relative to the dacarbazine-only group (61%)
      and even more tumor reduction (74%) compared with the control group. We also
      measured clearly reduced levels of tumor necrosis factor-alpha in the thalidomide
      treated group. A significantly lower microvessel density was encountered in the
      thalidomide treatment groups (thalidomide alone or combined with DTIC),
      underscoring the anti-angiogenic effect of thalidomide as a single agent as well
      as in combination with chemotherapy in this model. In line with these results, we
      observed a nearly 3-fold increase of apoptosis for the combination of thalidomide
      and DTIC compared with the rate of apoptotic cells in DTIC-only-treated melanoma
      xenotransplants. These data underline the rationale for combining dacarbazine--a
      cytotoxic agent--and thalidomide--an anti-angiogenic cytostatic agent--as a
      promising strategy for the treatment of melanoma.

PMID- 16098028
TI  - Naturally occurring proteasome inhibitors from mate tea (Ilex paraguayensis)
      serve as models for topical proteasome inhibitors.
AB  - Proteasome inhibitors have emerged as a clinically important therapy for
      neoplastic disease, with velcade, an organoboron compound used extensively in
      multiple myeloma. Recently, (-)-epigallocatechin gallate has been found to be a
      potent inhibitor of the proteasomal chymotrypsin-like activity. Other compounds
      that inhibit angiogenesis and are active as chemopreventive agents, such as
      curcumin, also inhibit proteasome activity. We have screened natural product
      extracts using ras-transformed endothelial cells (SVR cells) as a bioassay, and
      found that extracts of mate tea (Ilex paraguayensis) inhibit the growth of these
      endothelial cells. The extract was fractionated and found to have novel cinnamate
      esters that inhibit proteasome activity. Based upon the structures of the
      compounds isolated from mate tea, we examined synthetic analogs of these
      compounds for proteasome activity. Cinnamic acid amides had no inhibitory
      activity against proteasomes, whereas cinnamate esters displayed the activity.
      Based upon these findings, preclinical and clinical trials of topical cinnamate
      esters as proteasome inhibitors are warranted for psoriasis and other
      inflammatory disorders.

PMID- 16098029
TI  - Creatine supplementation normalizes mutagenesis of mitochondrial DNA as well as
      functional consequences.
AB  - Mutations of mitochondrial (mt) DNA play a role in neurodegeneration, normal
      aging, premature aging of the skin (photoaging), and tumors. We and others could
      demonstrate that mtDNA mutations can be induced in skin cells in vitro and in
      normal human skin in vivo by repetitive, sublethal ultraviolet (UV)-A
      irradiation. These mutations are mediated by singlet oxygen and persist in human
      skin as long-term biomarkers of UV exposure. Although mtDNA exclusively encodes
      for the respiratory chain, involvement of the energy metabolism in mtDNA
      mutagenesis and a protective role of the energy precursor creatine have thus far
      not been shown. We assessed the amount of a marker mutation of mtDNA, the so
      called common deletion, by real-time PCR. Induction of the common deletion was
      paralleled by a measurable decrease of oxygen consumption, mitochondrial membrane
      potential, and ATP content, as well as an increase of matrix metalloproteinase-1.
      Mitochondrial mutagenesis as well as functional consequences could be normalized
      by increasing intracellular creatine levels. These data indicate that increase of
      the energy precursor creatine protects from functionally relevant, aging
      associated mutations of mitochondrial DNA.

PMID- 16098030
TI  - H2O2 accumulation by catalase reduction changes MAP kinase signaling in aged
      human skin in vivo.
AB  - To understand the molecular alterations occurring during the aging process, we
      compared mitogen-activated protein (MAP) kinase activities in the intrinsically
      aged and photoaged skins in the same individuals. Furthermore, we investigated
      the molecular events related to MAP kinase changes in intrinsically aged and
      photoaged skins. We found that extracellular-signal-regulated kinase (ERK)
      activity in photoaged skin was reduced, and that the activities of c-Jun N
      terminal kinase (JNK) and p38 kinase were increased compared with intrinsically
      aged skin in the same individuals. Phospho-c-Jun levels and activator protein 1
      activities in photoaged skin were also higher than in intrinsically aged skin.
      Moreover, catalase activity was found to be much reduced in primary dermal
      fibroblasts from photoaged skin, and as a result, H2O2 accumulated more in
      primary dermal fibroblasts in photoaged skin. In addition, treating primary
      dermal fibroblasts from photoaged skin with catalase reduced H2O2 levels,
      reversed aging-dependent MAP kinase changes, and inhibited matrix
      metalloproteinase (MMP)-1 expression. Our results indicate that the accumulation
      of reactive oxygen species due to catalase attenuation may be a critical aspect
      of the MAP kinase signaling changes that may lead to skin aging and photoaging in
      human skin in vivo. Thus, the induction and regulation of endogenous antioxidant
      enzymes including catalase may offer a strategy for preventing and treating skin
      aging.

PMID- 16098031
TI  - Stratifin-induced matrix metalloproteinase-1 in fibroblast is mediated by c-fos
      and p38 mitogen-activated protein kinase activation.
AB  - Previously, we have demonstrated that keratinocyte releasable stratifin, also
      known as 14-3-3 sigma protein, stimulates matrix metalloproteinase (MMP)-1
      expression in dermal fibroblasts. In this study, we showed that stratifin induced
      fibroblast MMP-1 messenger ribonucleic acid (mRNA) and protein levels through p38
      mitogen-activated protein kinase (MAPK). Our data indicated that treatment of
      dermal fibroblasts with stratifin resulted in rapid and transient upregulation of
      c-jun and c-fos mRNA levels. We also demonstrated that SB203580 (SB), a specific
      inhibitor of p38 MAPK activity, inhibited the activation of fibroblast MMP-1 mRNA
      expression by stratifin. Subsequently, western blot analysis revealed
      phosphorylation of p38 at 90 min after stratifin stimulation and this was
      decreased to approximately 50% of the maximum value by 120 min. Stratifin was
      demonstrated to increase MMP-1 protein levels starting at 4 h and reaching its
      peak at 12-24 h. Furthermore, SB significantly blocked the stratifin induction of
      MMP-1 protein levels (***p<0.005, n=3). Microarray analysis of stratifin-treated
      fibroblasts shows an increase in Elk4/Sap1 mRNA expression and this finding was
      confirmed by northern blot analysis. Our results indicate that stratifin markedly
      increase Elk4/Sap1 mRNA expression in a time-dependent fashion. In conclusion,
      stratifin stimulates fibroblast MMP-1 levels through the activation of c-fos and
      MAPK pathway.

PMID- 16098032
TI  - Epidermolysis bullosa simplex: recurrent and de novo mutations in the KRT5 and
      KRT14 genes, phenotype/genotype correlations, and implications for genetic
      counseling and prenatal diagnosis.
AB  - Epidermolysis bullosa simplex (EBS) is a mechano-bullous disorder characterized
      by intraepidermal blistering within the basal keratinocytes as a result of trauma
      to the skin. As part of the DNA diagnostics program, our laboratory has analyzed
      a cohort of 57 patients with the initial referral diagnosis of EBS. Among these
      patients, 18 were found to harbor heterozygous mutations in the keratin 5 or
      keratin 14 genes, KRT5 and KRT14, respectively, whereas in 14 cases, the disease
      was associated with mutations in both alleles of the plectin gene. Among the
      keratin mutations, 12 were distinct and six were novel, and in most cases there
      was no family history of a blistering disease. Prenatal diagnosis of eight
      pregnancies with keratin gene mutations, at risk for EBS either because one of
      the parents was affected (three cases) or history of a previously affected child
      as a result of a de novo mutation (five cases), predicted two fetuses being
      affected and six being normal. No recurrence of the de novo mutations in these
      pregnancies was disclosed. Collectively, the data suggest that a significant
      number of cases diagnosed as EBS are due to plectin mutations, and many cases
      result from de novo mutations in KRT5 and KRT14 genes. These findings have
      implications for genetic counseling and prenatal diagnosis for EBS.

PMID- 16098033
TI  - A novel XPA gene mutation and its functional analysis in a Japanese patient with
      xeroderma pigmentosum group A.
AB  - Most Japanese patients with xeroderma pigmentosum group A (XPA) have the
      homozygous intron 3 splicing mutations (AlwNI mutation). Here, we report a
      Japanese XPA patient, XP79KO, a compound heterozygote with a newly identified T
      to G transversion at splice donor site in intron 1 in one allele, and with the
      AlwNI mutation in another allele in the XPA gene. The mutation in intron 1
      creates two new abnormal splice sites that resulted in two types of aberrant
      mRNA. These abnormal splicings cause frameshifts that make stop codons
      downstream. No XPA protein was detected in XP79KO fibroblasts.

PMID- 16098034
TI  - Increased phosphorylation and activation of mitogen-activated protein kinase p38
      in scleroderma fibroblasts.
AB  - Transforming growth factor-beta (TGF-beta) stimulates the transcription of the
      alpha2(I) collagen gene. The dermal fibroblast activation in systemic sclerosis
      (SSc) may be a result of stimulation by autocrine TGF-beta. In this study, we
      investigated whether p38 mitogen-activated protein kinase (MAPK) is involved in
      TGF-beta-induced transcriptional activation of the human alpha2(I) collagen gene
      in normal dermal fibroblasts and in upregulated extracellular matrix (ECM)
      expression in SSc fibroblasts. Type I collagen expression induced by TGF-beta was
      suppressed by the specific p38 MAPK inhibitors SB203580 or SB202190 in normal
      fibroblasts. TGF-beta induced phosphorylation and activation of p38 MAPK in
      normal dermal fibroblasts. Transient transfection of dominant-negative mutant p38
      MAPK into normal fibroblasts abolished TGF-beta-induced promoter activity of the
      human alpha2(I) collagen gene in normal fibroblasts. Moreover, constitutive
      phosphorylation and activation of p38 MAPK was demonstrated in SSc fibroblasts,
      and the inhibition of p38 MAPK using specific p38 MAPK inhibitors or dominant
      negative mutant p38 MAPK abolished the upregulated expression of type I collagen
      or fibronectin in SSc fibroblasts. These results strongly suggest the
      contribution of p38 MAPK signaling to the TGF-beta-mediated regulation of the
      human alpha2(I) collagen gene in normal dermal fibroblasts and constitutive
      upregulated expression of type I collagen and fibronectin in SSc fibroblasts.

PMID- 16098036
TI  - Differential stripping: determination of the amount of topically applied
      substances penetrated into the hair follicles.
AB  - The determination of penetration pathways of topically applied substances into
      the skin is the subject of several investigations. Recently, follicular
      penetration has become a major focus of interest. To date, a direct, non-invasive
      quantification of the amount of topically applied substance penetrated into the
      follicles had not been possible. The development of such a method was the aim of
      this study. Therefore, the advantages of both stripping techniques, tape
      stripping and cyanoacrylate skin surface biopsy, were combined and evaluated.
      Tape stripping was used to remove the part of the stratum corneum that contained
      the topically applied dye. Subsequently, the follicular contents were ripped off
      by cyanoacrylate skin surface biopsy. The combined method termed "differential
      stripping" was evaluated in vitro and in vivo, and the amount of topically
      applied fluorescent dye penetrated into the hair follicles was quantified after
      different penetration times. After 30 min, 5% of the recovered concentration of
      sodium fluorescein was found in the follicular infundibula, where it was still
      detectable after 48 h. Altogether, the results of this investigation revealed
      that differential stripping is a new method that can be used to study the
      penetration of topically applied substances into the follicular infundibula non
      invasively and selectively.

PMID- 16098035
TI  - Granulysin-derived peptides demonstrate antimicrobial and anti-inflammatory
      effects against Propionibacterium acnes.
AB  - Propionibacterium acnes is a key therapeutic target in acne, yet this bacterium
      has become resistant to standard antibiotic agents. We investigated whether the
      human antimicrobial protein granulysin is a potential candidate for the treatment
      of acne. Granulysin and synthetic granulysin-derived peptides possessing a helix
      loop-helix motif killed P. acnes in vitro. Modification of a helix-loop-helix
      peptide, 31-50, by substitution of a tryptophan for the valine at amino acid 44
      (peptide 31-50v44w) to increase its interaction with bacterial surfaces also
      increased its antimicrobial activity. Moreover, when synthesized with D- rather
      than L-type amino acids, this peptide (D-31-50v44w) became less susceptible to
      degradation by proteases and more effective in killing P. acnes. Granulysin
      peptides were bactericidal, demonstrating an advantage over standard
      bacteriostatic antibiotics in their control of P. acnes. Moreover, peptide D-31
      50v44w killed P. acnes in isolated human microcomedone preparations. Importantly,
      peptides 31-50, 31-50v44w, and D-31-50v44w also have potential anti-inflammatory
      effects, as demonstrated by suppression of P. acnes-stimulated cytokine release.
      Taken together, these data suggest that granulysin peptides may be useful as
      topical therapeutic agents, providing alternatives to current acne therapies.

PMID- 16098037
TI  - Slow internal release of bioactive compounds under the effect of skin enzymes.
AB  - A new strategy for the skin delivery of bioactive compounds has been developed,
      using enzymes involved in the maintenance of the epidermal barrier function and
      the enzymatic transformation of corresponding precursors. This new strategy has
      been tested with regard to two enzymatic activities of the skin barrier:
      extracellular glucosidase and esterase/lipase. An analysis of the requirements
      for the glycosidic bond hydrolysis of any glycoconjugate by beta
      glucocerebrosidase indicates that the release of the moiety linked to the glucose
      unit is obtained as long as the glycosidic bond being broken is not hindered, and
      as long as the leaving group property of the released moiety is good enough. This
      strategy was first applied to the release of the antioxidant delta-tocopherol. It
      was then extended to retinoic acid by introducing a spacer between the glucose
      unit and the bioactive moiety. This spacer was either a good leaving group such
      as hydroquinone, or a structure akin to a ceramide, namely glycerol. In these
      conditions, beta-glucocerebrosidase releases the complex spacer-active compound
      that is cleaved by an esterase. One of the advantages of this strategy lies in
      the slow release of the bioactive compound, extending in time its effect and most
      likely its tolerance, as is the case for retinoic acid.

PMID- 16098038
TI  - Identification and characterization of a novel retroviral-like aspartic protease
      specifically expressed in human epidermis.
AB  - Proteases play a pivotal role in epidermal differentiation and desquamation.
      Separation of a total protein extract from human reconstructed epidermis by two
      dimensional gel electrophoresis and subsequent peptide analysis of a specific
      protein spot identified a new protein exhibiting similarities with the retroviral
      aspartic protease family. Cloning of the corresponding full-length cDNA revealed
      an open reading frame encoding for a new protease of 343 amino acids, containing
      a putative aspartic protease catalytic domain. We named this protein Skin
      ASpartic Protease (SASPase). RT-PCR and northern blot analysis of various human
      tissues revealed that SASPase was specifically expressed within the epidermis.
      Immunohistochemical analysis showed a particularly intense expression restricted
      to the granular layers, whereas in diseased skin, its expression was changed.
      Western blot analysis, using a monoclonal antibody, revealed the expression of
      two forms of the enzyme: a 28 kDa putative proform and the active 14 kDa form.
      Recombinant truncated SASPase (SASP28) was generated from a prokaryotic
      expression system in Escherichia coli as a fusion protein with GST. SASP28
      degraded insulin and to a lesser extent casein with a pH optimum of 5. As seen
      for retroviral proteases, an auto-activation processing was evidenced, generating
      a 14 kDa protein (SASP14). Site-directed mutagenesis inhibited auto-activation of
      the enzyme. Indinavir, a potent HIV protease inhibitor used in AIDS therapy, had
      a significant inhibitory effect on rSASPase auto-activation, which could explain
      its side effects on skin.

PMID- 16098039
TI  - Is endogenous glycerol a determinant of stratum corneum hydration in humans?
AB  - Although stratum corneum (SC) hydration has been primarily of concern to the
      cosmetic industry, it serves an important biosensor function. In murine models,
      not only deiminated products of filaggrin-derived amino acids ("NMF") but also
      endogenous glycerol from circulation into the epidermis via aquaporin 3 channel
      and from triglyceride turnover in sebaceous glands (SG) are important
      determinants. We assessed here whether endogenous glycerol could also be linked
      to SC hydration in humans. SG-enriched sites are more hydrated than SG
      impoverished sites, and SC hydration correlates with both sebum production and SC
      glycerol content, but the correlation is more significant for SC glycerol content
      than for sebum content. Moreover, gender-related differences in sebum content are
      not associated with altered SC hydration. SC hydration is also linked to SC
      glycerol content in SG-impoverished sites, suggesting a role for non-SG-derived
      (? from circulation) glycerol in SC hydration. Finally, short-term water
      immersion produces a parallel decline in SC hydration and SC glycerol content,
      with glycerol levels returning to normal over several hours. These results
      suggest that endogenous glycerol of both circulatory and SG origin comprises an
      H2O-extractable pool that influences SC hydration in humans. These results also
      provide a rationale for the development of glycerol-containing therapeutic
      moisturizers.

PMID- 16098040
TI  - Regulation of protein kinase D during differentiation and proliferation of
      primary mouse keratinocytes.
AB  - Diseased skin often exhibits a deregulated program of the keratinocyte maturation
      necessary for epidermal stratification and function. Protein kinase D (PKD), a
      serine/threonine kinase, is expressed in proliferating keratinocytes, and PKD
      activation occurs in response to mitogen stimulation in other cell types. We have
      proposed that PKD functions as a pro-proliferative and/or anti-differentiative
      signal in keratinocytes and hypothesized that differentiation inducers will
      downmodulate PKD to allow differentiation to proceed. Thus, changes in PKD
      levels, autophosphorylation, and activity were analyzed upon stimulation of
      differentiation and proliferation in primary mouse keratinocytes. Elevated
      extracellular calcium and acute 12-O-tetradecanoylphorbol-13-acetate (TPA)
      treatments induced differentiation and triggered a downmodulation of PKD levels,
      autophosphorylation at serine 916, and activity. Chronic TPA treatment stimulated
      proliferation and resulted in a recovery of PKD levels, autophosphorylation, and
      activity. Immunohistochemical analysis demonstrated PKD localization
      predominantly in the proliferative basal layer of mouse epidermis. Co-expression
      studies revealed a pro-proliferative, anti-differentiative effect of PKD on
      keratinocyte maturation as monitored by increased and decreased promoter
      activities of keratin 5, a proliferative marker, and involucrin, a
      differentiative marker, respectively. This work describes the inverse regulation
      of PKD during keratinocyte differentiation and proliferation and the pro
      proliferative/anti-differentiative effects of PKD co-expression on keratinocyte
      maturation.

PMID- 16098041
TI  - Endothelin-1 induces CXCL1 and CXCL8 secretion in human melanoma cells.
AB  - The endothelin pathway plays a critical role in melanoma tumor progression by a
      variety of mechanisms that enhance tumor cell growth, invasion, and metastasis.
      Here, we investigate the effect of this pathway on CXC chemokine expression in
      human melanoma cells and melanocytes. As determined by ELISA, endothelin-1 (ET-1)
      induces CXCL1 and CXCL8 secretion in three human melanoma cell lines in a
      concentration-dependent fashion. These responses are mediated by the endothelin-B
      receptor and are sustained over a 40 h time course. ET-1 does not induce CXCL1
      secretion in primary human melanocytes but ET-3, an endothelin isoform, induces a
      low level of CXCL1 secretion in certain cultures. Neither ET-1 nor ET-3 induces
      secretion of CXCL8 in primary human melanocytes; thus, this response may be
      specific for melanocytic cells that have undergone malignant transformation. We
      have previously demonstrated that ET-1 induces changes in the expression of
      adhesion molecules in melanoma cells such that invasion and metastasis are
      favored. This study demonstrates that ET-1 additionally induces secretion of CXC
      chemokines critical for melanoma metastasis and tumor progression.

PMID- 16098042
TI  - BRAF and NRAS mutations are frequent in nodular melanoma but are not associated
      with tumor cell proliferation or patient survival.
AB  - Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma
      viral oncogene homolog B1) or NRAS (neuroblastoma RAS viral [V-ras] oncogene
      homolog) genes in cutaneous melanoma, but the relationship between these
      alterations and tumor cell proliferation has not been examined in human melanoma.
      In our study of 51 primary nodular melanomas and 18 paired metastases, we found
      mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%)
      and eight metastases (44%). The figures for NRAS mutations were 27% and 22%,
      respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but
      one case, and were maintained from primary tumors through their metastases.
      Mutations, however, were not associated with tumor cell proliferation by Ki-67
      expression, tumor thickness, microvessel density, or vascular invasion, and there
      were no differences in patient survival. Although BRAF and NRAS mutations are
      likely to be important for the initiation and maintenance of some melanomas,
      other factors might be more significant for proliferation and prognosis in
      subgroups of aggressive melanoma.

PMID- 16098043
TI  - Constitutive activation of the mitogen-activated protein kinase signaling pathway
      in acral melanomas.
AB  - One of the most attractive clinical targets for melanoma is the mitogen-activated
      protein kinase (MAPK) signaling pathway. In this study, we examined MAPK
      signaling activation in a total of 28 acral melanoma samples, consisting of 13
      primary tumors and 15 metastases. In line with the previous reports, NRAS/BRAF
      mutations were rare; only one metastatic tumor had an NRAS E61R mutation, and one
      primary tumor and two metastases harbored BRAF V599E mutations. Western blot
      analyses, however, revealed phosphorylated extracellular signal-regulated kinase
      (ERK)1/2 proteins in 11 of 14 (78.5%) of the acral melanoma tumors. Furthermore,
      fluorescence in situ hybridization analyses revealed the prominent amplification
      of the cyclin D1 (CCND1) gene, which is an important down-stream effecter of the
      MAPK pathway, in 5 of 21 (23.8%) tumors examined. Interestingly, two of three
      tumors that were negative for phosphorylated ERK proteins according to western
      blot harbored CCND1 amplifications, suggesting that the increased gene dosage of
      CCND1 may exert effects similar to phosphorylated ERK proteins in cell growth. We
      conclude that, despite the low frequency of BRAF/NRAS mutations, the MAPK
      signaling pathway is constitutively activated in the majority of acral melanomas.
      This provides a rational basis to include acral melanomas into the clinical
      trials with MAPK inhibitors.

PMID- 16098044
TI  - Ultraviolet light (UVB and UVA) induces the damage-responsive transcription
      factor CHOP/gadd153 in murine and human epidermis: evidence for a mechanism
      specific to intact skin.
AB  - C/EBP-homologous protein (CHOP)/gadd153 (or CHOP) is a transcription factor
      induced by endoplasmic reticulum (ER) stress. Forcible overexpression of CHOP
      causes apoptosis in keratinocytes in culture. Here, we asked whether CHOP might
      be increased in the skin after UVB (280-320 nm) exposure, thus implicating CHOP
      in sunburn cell (SBC) formation. SKH-1 hairless mice were exposed to a
      ultraviolet (UV) source (80 mJ per cm2; approximately 74% UVB, approximately 16%
      UVA), and skin biopsies examined by immunohistology and immunoprecipitation.
      Compared with non-irradiated epidermis, CHOP expression was significantly
      increased at 30 min, and reached maximal levels by 24 h. Similar increases in
      CHOP following UVB exposure were observed in human buttock skin. The time course
      of CHOP expression preceded SBC formation and another marker of apoptosis,
      caspase-3 cleavage. Intracellular CHOP accumulated mainly in cytoplasmic and
      perinuclear locations, with little remaining in the nucleus. To examine
      mechanisms, cultured keratinocytes were irradiated in vitro and examined by
      western blotting. Under conditions that eliminated ER stress because of cell
      handling, CHOP did not accumulate (and was in fact decreased) in the cells. Thus,
      induction of CHOP in keratinocytes requires factors present only in the native
      skin. Overall, the data suggest that CHOP participates in adaptive responses of
      the epidermis following UVB/UVA exposure in vivo.

PMID- 16098045
TI  - Solar-simulated ultraviolet radiation induces abnormal maturation and defective
      chemotaxis of dendritic cells.
AB  - Exposure to ultraviolet (UV) light induces immunosuppression. Different evidences
      indicate that this phenomenon is mainly a consequence of the effect of UV light
      on skin dendritic cells (DC). To investigate the cellular and molecular basis of
      this type of immunosuppression, we assessed in vitro the effect of solar
      simulated UV radiation on the phenotypic and functional characteristics of human
      monocyte-derived DC and Langerhans-like DC. UV radiation induced a decreased
      expression of molecules involved in antigen capture as DC-SIGN and the mannose
      receptor. This effect was accompanied by a diminished endocytic capacity, an
      enhanced expression of molecules involved in antigen presentation such as major
      histocompatibility complex-II and CD86, and a significant increase in their
      capability to stimulate T cells. Furthermore, irradiated DC failed to acquire a
      full mature phenotype upon treatment with lipopolysaccharide. On the other hand,
      solar-simulated radiation induced the secretion of tumor necrosis factor-alpha
      and interleukin (IL)-10 by DC, but no IL-12. Interestingly, solar-simulated UV
      radiation also caused an altered migratory phenotype, with an increased
      expression of CXCR4, and a lack of induction of CCR7, thus correlating with a
      high chemotactic response to stromal cell-derived factor 1(SDF-1) (CXCL12), but
      not to secondary lymphoid tissue chemokine (SLC) (CCL21). These data indicate
      that solar-simulated UV radiation induces a defective maturation and an anomalous
      migratory phenotype of DC.

PMID- 16098046
TI  - Selective photothermolysis of blood vessels following flashlamp-pumped pulsed dye
      laser irradiation: in vivo results and mathematical modelling are in agreement.
AB  - Laser therapy using the pulsed dye laser is the standard treatment for port-wine
      stains (PWS). But the mechanism of action has not been elucidated completely,
      yet. The dorsal skin-fold chamber model in hamsters was used to investigate the
      effects of laser treatment (lambda(em)=585 nm; pulse duration: 0.45 ms; fluence:
      6 J per cm2) on blood vessels. Vessels (n=3394) were marked with FITC dextran (MW
      150 kDa) and diameters (2-186 microm) were measured using intravital fluorescence
      microscopy up to 24 h following irradiation. Histology (H&E, TUNEL, CD31) was
      taken 1 or 24 h after irradiation. The experimental results were compared with
      the predictions of a mathematical model based on the finite-element method.
      Following irradiation treatment the number of unperfused vessels decreases with
      decreasing vessel diameter in vivo. Histology indicated a restriction of tissue
      injury to the irradiated area after 1 h. Blood vessels contained aggregated red
      blood cells. After 24 h tissue damage occurred also outside the irradiated area
      and thrombus formation was visible. These results were in agreement with the
      mathematical calculations. In addition to initial physical effects after pulsed
      dye laser treatment delayed biological processes contribute significantly to the
      reduction of perfused blood vessels. Because of incomplete photocoagulation of
      smaller blood vessels (diameter 2-16 microm) a complete bleaching of PWS seems to
      be unlikely.

PMID- 16098047
TI  - Expression of gp130 in tumors and inflammatory disorders of the skin: formal
      proof of its identity as CD146 (MUC18, Mel-CAM).
AB  - Two antibodies, BT14 and L101, detect a tumor-associated cell surface
      glycoprotein (gp130) whose properties in normal and diseased skin were assessed,
      and whose molecular identity was determined in this study. In normal skin, gp130
      was constitutively expressed on dermal blood vessels and epidermal appendages,
      but not in interfollicular epidermis. Marked induction was detected within benign
      and malignant tumors of various origins including viral warts, basal cell
      carcinomas, squamous cell carcinomas, metastatic melanomas, and cutaneous T cell
      lymphomas. In vitro studies confirmed the general upregulation of gp130
      expression in malignantly transformed cells. Surprisingly, gp130 was also induced
      in inflammatory skin diseases including psoriasis and allergic contact
      dermatitis. Halting proliferation of transformed keratinocytes through cytostatic
      drugs or increasing the Ca2+ concentration in the medium resulted in increased
      gp130 expression. In addition, overexpression of Bcl-2 led to upregulation of
      gp130. When the protein was purified and analyzed by peptide mass fingerprinting,
      we could demonstrate that it is MUC18 (Mel-CAM, CD146). Sequential
      immunoprecipitations and western blot analyses confirmed the identity of the
      antigen. Thus, both expression pattern and regulation characteristics of the now
      known glycoprotein gp130 extended beyond previously published data regarding
      MUC18, thus shedding some new light on a supposedly well-known antigen.

PMID- 16098048
TI  - An in vivo mouse model of human skin substitute containing spontaneously sorted
      melanocytes demonstrates physiological changes after UVB irradiation.
AB  - Human skin substitutes (HSS) have been developed for repairing burns and other
      acute or chronic wounds. But although the clinical utility of HSS is well known,
      scant attention has been paid to their cosmetic properties, especially with
      regard to color compatibility with the patient's complexion. In this study, we
      generated an HSS from mixed cell slurries containing keratinocytes and
      fibroblasts with and without melanocytes on the back of severe combined
      immunodeficient mice by means of a spontaneous cell-sorting technique. At 16 wk
      after grafting, Caucasian donor-derived HSS with melanocytes were macroscopically
      clearly darker than those without melanocytes, and a more darkly pigmented HSS
      was produced when cells from donors of African descent were seeded.
      Immunohistochemistry of c-kit, S-100, and HMB45, as well as Fontana-Masson
      staining and transmission electron microscopy (TEM) demonstrated that melanocytes
      spontaneously localized to the basal layer. Melanosome transfer to keratinocytes
      was correctly reorganized, and melanin was evenly dispersed in the basal and
      suprabasal layers. Colorimetric analysis showed a significantly lower L-value by
      day 14 following irradiation with 120 mJ per cm2 ultraviolet-B (UVB) (p<0.01),
      whereas epidermal thickness increased by 50% 1 d after exposure (p<0.01),
      indicating a normal physiological response to UVB irradiation. These findings
      suggest that HSS with spontaneously sorted melanocytes offer a means of treating
      both the structural and cosmetic aspects of skin conditions and trauma, such as
      pigmentary disorders and skin wounds, by allowing manipulation of the color and
      population of donor melanocytes.

PMID- 16098049
TI  - Abnormal extracellular matrix metabolism in chronically ischemic skin: a
      mechanism for dermal failure in leg ulcers.
AB  - Extracellular matrix (ECM) metabolism and homeostasis is sensitive to changes in
      oxygen tension manifest in ischemia. We hypothesize that in chronically ischemic
      limbs, abnormalities in uninjured skin, secondary to hypoxia, predispose to
      dermal breakdown. Paired biopsies of uninjured distal ischemic and proximal non
      ischemic skin were harvested at below knee amputation from 14 patients with
      peripheral vascular disease following quantification of ischemia. Age- and site
      matched controls were taken at total knee replacement (TKR) and varicose vein
      (VV) operations. Matrix metalloproteinase (MMP)-2 and -9 expression was
      determined using gelatin zymography, MMP-1 by western blotting and ELISA and
      tissue inhibitor of MMP (TIMP) by reverse zymography. Collagen content was
      measured by determining hydroxyproline levels, and collagen type I synthesis by
      ELISA. Collagen type I synthesis was upregulated in ischemic tissue compared with
      non-ischemic matched pairs (p<0.001) and both TKR and VV controls, however, there
      was no increase in collagen deposition. Levels of MMP-2 (p<0.0005) and TIMP-2
      (p<0.01), were elevated in ischemic samples. MMP-9 was unaltered, signifying no
      inflammatory changes. Tissue ischemia was linked to elevated ECM turnover,
      associated with matrix failure when compounded with problems of matrix
      stabilization, likely in ischemia. This represents a potential mechanism for
      ulcer formation.

PMID- 16098050
TI  - Brain activation by histamine prick test-induced itch.

PMID- 16098051
TI  - SCA-1+ cells with an adipocyte phenotype in neonatal mouse skin.

PMID- 16098052
TI  - Role of apaf-1 in melanoma drug resistance and apoptosis.

PMID- 16098053
TI  - Candidate functional promoter variant in the FOXD3 melanoblast developmental
      regulator gene in autosomal dominant vitiligo.

PMID- 16098054
TI  - Constitutive expression of epidermal growth factor receptors on normal human
      melanocytes.

PMID- 16098055
TI  - Protein tyrosine phosphatase gene PTPN22 polymorphism in psoriasis: lack of
      evidence for association.

PMID- 16098056
TI  - Five novel mutations in tyrosinase gene of Japanese and Indian patients with
      oculocutaneous albinism type I (OCA1).

PMID- 16098057
TI  - Absence of association between asthma and high serum immunoglobulin E associated
      GPRA haplotypes and adult atopic dermatitis.

PMID- 16098058
TI  - Bone marrow necrosis.

PMID- 16098059
TI  - Air embolism simulating atypical pneumonia.

PMID- 16098060
TI  - Normal and leukaemic stem cells.
AB  - The blood-related cancer leukaemias were the first diseases where human cancer
      stem cells, or leukaemic stem cells (LSC), were isolated. The haematopoietic
      system is one of the best tissues for investigating cancer stem cells, because
      the developmental hierarchy of normal blood formation is well defined. Leukaemias
      can now be viewed as aberrant haematopoietic processes initiated by rare LSC that
      have maintained or reacquired the capacity for indefinite proliferation through
      accumulated mutations and/or epigenetic changes. Yet, despite their critical
      importance, much remains to be learned about the developmental origin of LSC and
      the mechanisms responsible for their emergence in the course of the disease. This
      report will review our current knowledge on normal and LSC development and
      examine the impact of these discoveries may have clinically and in our
      understanding of the leukaemogenic process.

PMID- 16098061
TI  - Continuing challenges in childhood non-Hodgkin's lymphoma.
AB  - Non-Hodgkin's lymphoma in children includes a number of different pathological
      subtypes and, with improved diagnostic techniques and better understanding of the
      natural history of each type, treatment strategies have become more tumour
      specific. Original staging systems are now less useful in determining treatment
      stratification and there is a need for careful analysis of large cohorts of
      patients, treated in the same manner, to determine the clinical and biological
      features that, with current therapies, are of prognostic value. Novel imaging
      techniques, such as positron emission tomography, and molecular techniques to
      detect low-level marrow involvement are likely to be incorporated into new risk
      grouping. These will be used to determine the extent of initial disease and
      evaluate more accurately the speed and quality of response to chemotherapy. With
      high cure rates, it becomes particularly important to minimize late effects of
      therapy and the introduction of monoclonal antibodies in combination with
      chemotherapy may provide a method for improving outcome in poor risk groups and
      reducing sequelae by allowing reduction in chemotherapy in good risk patients.

PMID- 16098062
TI  - Philadelphia positive acute lymphoblastic leukaemia of childhood.
AB  - On current chemotherapeutic regimens, children with Philadelphia positive acute
      lymphoblastic leukaemia show a heterogeneous response to treatment. A few respond
      quickly to treatment and achieve long-term remission. Some fail to achieve
      remission after induction and the majority respond slowly to treatment. Relapse
      on treatment is common and remission is sustained in a proportion of cases only
      after allogeneic stem cell transplantation (allo-SCT). The use of imatinib along
      with conventional cytoreductive therapy, prior to allo-SCT appears to be the most
      promising strategy. The future lies in the molecular evaluation of response to
      treatment and combination targeted chemotherapy.

PMID- 16098063
TI  - Activity of selective fully human agonistic antibodies to the TRAIL death
      receptors TRAIL-R1 and TRAIL-R2 in primary and cultured lymphoma cells: induction
      of apoptosis and enhancement of doxorubicin- and bortezomib-induced cell death.
AB  - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a death
      protein that preferentially kills tumour cells while sparing normal cells. TRAIL
      has four exclusive receptors, two of which (TRAIL-R1, TRAIL-R2) are death
      receptors. Both TRAIL/Apo2L and agonistic antibodies to the TRAIL death receptors
      are currently being explored for cancer therapy. Although the activity of
      TRAIL/Apo2L in a variety of haematological malignancies has been examined, the
      activity of anti-TRAIL receptor agonistic antibodies in primary and cultured
      lymphoma cells has not. Using two fully human selective agonistic monoclonal
      antibodies to the TRAIL death receptors TRAIL-R1 (HGS-ETR1) and TRAIL-R2 (HGS
      ETR2) this study demonstrated that both monoclonal antibodies activated caspase-8
      and induced cell death in five of nine human lymphoma cell lines, and induced
      >10% cell death in 67% and 70%, respectively, of 27 primary lymphoma cells, and
      >20% cell death in at least one-thirds of the samples. HGS-ETR1 and HGS-ETR2
      demonstrated comparable activity in the fresh tumour samples, which was
      independent of TRAIL receptor surface expression, Bax, cFLIP, or procaspase-8
      expression, or exposure to prior therapy. Furthermore, both antibodies enhanced
      the killing effect of doxorubicin and bortezomib. Our data demonstrate that HGS
      ETR1 and HGS-ETR2 monoclonal antibodies can induce cell death in a variety of
      cultured and primary lymphoma cells, and may have therapeutic value in lymphoma.

PMID- 16098064
TI  - Isolated central nervous system involvement in adult T-cell lymphoma/leukaemia.
AB  - Central nervous system (CNS) presentation of adult T-cell lymphoma/leukaemia is
      rare, and almost invariably associated with systemic disease. We report an
      unusual manifestation of adult T-cell lymphoma/leukaemia, with isolated CNS
      involvement and unusual imaging findings. We also describe objective response to
      antiviral therapy. To our knowledge, this is the first report of such
      presentation and response.

PMID- 16098065
TI  - Gene expression profiling of mantle cell lymphoma cells reveals aberrant
      expression of genes from the PI3K-AKT, WNT and TGFbeta signalling pathways.
AB  - Microarray studies have revealed the differential expression of several genes in
      mantle cell lymphoma (MCL), but it is unknown which of these differences are
      dependent on the transformed MCL cell itself or on the tumour microenvironment.
      To investigate which genes and signalling pathways are aberrantly expressed in
      MCL cells we used oligonucleotide microarrays to perform gene expression
      profiling of both purified leukaemic MCL cells and their normal counterparts, the
      naive B cells. A total of 106 genes were differentially expressed at least
      threefold in MCL cells compared with naive B cells; 63 upregulated and 43
      downregulated. To validate the microarray results in a larger set of samples, we
      selected 10 differentially expressed genes and quantified their expression by
      real-time polymerase chain reaction in peripheral blood of MCL patients (n=21),
      purified MCL cells (n=6) and naive B cells (n=4), obtaining fully concordant
      results. A computer-assisted approach was used to procure specific molecular
      signalling pathways that were aberrantly expressed in MCL cells. Several genes
      related to apoptosis and to the PI3K/AKT, WNT and tumour growth factor beta
      signalling pathways were altered in MCL cells when compared with naive B cells.
      These pathways may play a significant role in the pathogenesis of MCL and deserve
      further investigation as candidates for new therapeutic targets.

PMID- 16098066
TI  - Viscum album agglutinin-I induces apoptosis and degradation of cytoskeletal
      proteins via caspases in human leukaemia eosinophil AML14.3D10 cells: differences
      with purified human eosinophils.
AB  - Although there are several agents that induce neutrophil apoptosis, few are known
      as inducers of eosinophil apoptosis. As eosinophils are potent effector cells
      contributing to allergic inflammation and asthma, we investigated whether the pro
      apoptotic agent Viscum album agglutinin-I (VAA-I) could induce eosinophil
      apoptosis. VAA-I was found to induce apoptosis in eosinophilic AML14.3D10 (3D10)
      cells and that these cells expressed caspases-1, -2, -3, -4, -7, -8, -9 and -10.
      VAA-I-induced gelsolin degradation was reversed by the pan-caspase inhibitor N
      benzyloxycarbonyl-V-A-D-O-methylfluoromethyl ketone (z-VAD). Also, paxillin,
      vimentin and lamin B1 were cleaved by caspases in VAA-I-induced 3D10 cells. VAA-I
      activated caspase-3 and -8 in 3D10 cells but, unlike z-VAD, treatment with a
      caspase-8 inhibitor slightly reversed apoptosis. Treatment of purified human
      eosinophils with VAA-I was found to induce apoptosis, degradation of gelsolin and
      lamin B1, but unlike 3D10 cells, cleavage of lamin B1 and cell apoptosis was not
      reversed by z-VAD. We conclude that VAA-I is a potent inducer of eosinophil
      apoptosis and that proteases other than those inhibited by z-VAD in 3D10 cells
      are involved in VAA-I-induced peripheral blood eosinophil apoptosis and lamin B1
      cleavage. Thus, VAA-I represents a potential candidate for the reduction of the
      number of eosinophils in diseases where they play important roles.

PMID- 16098067
TI  - Comparison of CHOP versus CIOP in good prognosis younger patients with
      histologically aggressive non-Hodgkin lymphoma.
AB  - CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) has been the
      standard chemotherapy regimen used for diffuse large cell lymphomas for over 30
      years. Idarubicin is a 4-demethoxy-anthracycline analogue of daunorubicin that
      has proven activity in non-Hodgkin lymphoma, and has been reported to cause less
      cardiotoxicity. We therefore initiated a randomised trial of standard dose CHOP
      versus CIOP (cyclophosphamide, idarubicin, vincristine and prednisolone), in
      which doxorubicin 50 mg/m2 was substituted by idarubicin 10 mg/m2, a dose thought
      to have equivalent anti-lymphoma activity. This trial was closed prematurely
      after 211 patients had completed therapy when a lower complete remission (CR)
      rate was noted in the CIOP arm. The formal results with long-term follow up are
      now reported. Overall response rate was 84% in the CHOP arm and 78% in the CIOP
      arm, CR rates were 70% and 52% respectively in all patients (P=0.013) and 73% and
      52% respectively for the eligible patients (P=0.0084). At a median of 8 years
      follow-up, 4-year progression-free survival for all patients was 56% in the CHOP
      arm and 40% in the CIOP arm (P=0.0096). Overall survival for all patients was 65%
      in the CHOP arm and 56% in the CIOP arm (P=0.14). Results for eligible patients
      were comparable. CIOP containing idarubicin at a dose of 10 mg/m2 is clearly
      inferior to standard CHOP.

PMID- 16098068
TI  - Soluble syndecan-1 level at diagnosis is an independent prognostic factor in
      multiple myeloma and the extent of fall from diagnosis to plateau predicts for
      overall survival.
AB  - Syndecan-1 (CD138) is a heparin sulphate proteoglycan that is over expressed on
      the surface of both normal and malignant plasma cells and actively shed from the
      cell surface (soluble syndecan-1). Soluble syndecan-1 has been shown to be an
      independent prognostic factor in myeloma but its role in prognostic
      classification requires further investigation. We have retrospectively measured
      soluble syndecan-1 in 324 presentation samples and 154 plateau phase samples from
      the UK Medical Research Council Myeloma VIth trial. Log-rank analysis showed that
      the presentation value of soluble syndecan-1 is a highly significant prognostic
      factor when assessing survival from entry (chi2=14.92, P<0.0001) and remains an
      important independent prognostic factor when considered in Cox regression models
      (P<or=0.02) with known independent factors. The magnitude of fall in soluble
      syndecan-1 from presentation to plateau also had prognostic value when assessing
      overall survival from plateau (chi2=3.79, P=0.05). In conclusion, this large
      study confirms that soluble syndecan-1 level is a powerful independent prognostic
      factor both at diagnosis and at plateau phase.

PMID- 16098069
TI  - The prognostic value of CD38 expression in chronic lymphocytic leukaemia patients
      studied prospectively at diagnosis: a single institute experience.
AB  - The purpose of this study was to assess in chronic lymphocytic leukaemia (CLL)
      patients the prevalence and clinical impact of CD38 expression, evaluated
      prospectively at disease presentation, and to verify whether this parameter
      changes over time. In 242 consecutive and untreated CLL patients, the percentage
      of CD38+ cases, according to the 7%, 20% and 30% cut-off points, was 21%, 17% and
      14%, respectively. Using the 7% threshold, CD38 positivity correlated with male
      sex, intermediate and high-risk (Rai I-IV) disease, lower Hb and platelet levels,
      and higher lymphocyte count. Furthermore, patients with a CD38 expression>or=7%
      showed a significantly lower 3-year probability of treatment-free survival (TFS)
      than CD38- patients (P<0.0001). At multivariate analysis, CD38 expression
      remained significantly associated to TFS, together with stage, lymphocyte count
      and morphology. Also, in the 146 patients with stage 0 CLL a CD38
      expression>or=7% identified a subgroup of patients with a significantly lower 3
      year probability of TFS (P=0.0005). Furthermore, this parameter did not change in
      30 of 31 (97%) re-evaluated patients. In conclusion, this study indicates that,
      when tested at diagnosis and on fresh material, a CD38 expression>or=7% is an
      important parameter for the identification of early CLL patients with more
      aggressive disease and that its expression remains stable over time.

PMID- 16098070
TI  - Zoledronate synergises with imatinib mesylate to inhibit Ph primary leukaemic
      cell growth.
AB  - We examined the in vivo effects and safety of the third generation
      bisphosphonate, zoledronate (ZOL) alone and combined with imatinib mesylate
      against primary Philadelphia chromosome positive (Ph+) leukaemic cells. ZOL
      inhibited the prenylation of Rap1A in leukaemic cells in vitro and synergised
      with imatinib to enhance the survival of mice engrafted with cells from imatinib
      responders, but not from non-responders because of mutated BCR-ABL. These
      findings suggest that the combination of ZOL and imatinib accelerate the
      eradication of Ph+ clone, resulting in better prognosis of Ph+ leukaemia patients
      who have not yet acquired mutations.

PMID- 16098071
TI  - Allogeneic haematopoietic stem cell transplantation as a promising treatment for
      natural killer-cell neoplasms.
AB  - The efficacy of allogeneic haematopoietic stem-cell transplantation (allo-HSCT)
      for natural killer (NK)-cell neoplasms is unknown. We investigated the results of
      allo-HSCT for NK-cell neoplasms between 1990 and 2003 through questionnaires.
      After reclassification by a haematopathologist, of 345 patients who underwent
      allo-HSCT for malignant lymphoma, 28 had NK-cell neoplasms (World Health
      Organization classification): extranodal NK/T-cell lymphoma (n=22), blastic NK
      cell lymphoma (n=3), and aggressive NK-cell leukaemia (n=3). Twelve were
      chemosensitive and 16 chemorefractory. Twenty-two had matched-related donors.
      Stem-cell source was bone marrow in eight and mobilised peripheral blood in 20.
      Conditioning regimens were myeloablative (n=23) and non-myeloablative (n=5).
      Grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD developed in 12
      and 8 respectively. Eight died of disease progression, three of infection, two of
      acute GVHD, one of veno-occlusive disease, one of interstitial pneumonitis, and
      one of thrombotic microangiopathy. Two-year progression-free and overall
      survivals were 34% and 40% respectively (median follow-up, 34 months). All
      patients who did not relapse/progress within 10 months achieved progression-free
      survival (PFS) during the follow-up. In multivariate analysis, stem cell source
      (BM versus peripheral blood; relative risk 3.03), age (>or=40 years vs. <40
      years; relative risk 2.85), and diagnoses (extranodal NK/T-cell lymphoma versus
      others; relative risk 3.94) significantly affected PFS. Allo-HSCT is a promising
      treatment for NK-cell neoplasms.

PMID- 16098072
TI  - Efficacy of the interleukin-2 receptor antagonist basiliximab in steroid
      refractory acute graft-versus-host disease.
AB  - Acute graft-versus-host disease (aGVHD) occurs in up to 80% of patients who
      undergo allogeneic stem cell transplantation (SCT) and contributes significantly
      to transplant-related mortality (TRM). We conducted a prospective phase II trial
      to assess the efficacy and feasibility of treating steroid-refractory aGVHD with
      basiliximab, a chimaeric monoclonal antibody directed against the alpha chain of
      the interleukin-2 (IL-2) receptor. Basiliximab was administered intravenously at
      a dose of 20 mg on days 1 and 4. Twenty-three patients were enrolled between
      October 1999 and July 2004. We found a primary overall response rate of 82.5%
      with four patients (17.5%) showing a complete response and 15 patients (65%) a
      partial response. Six patients were again treated successfully with an IL-2
      receptor antagonist because of recurrence of aGVHD. The rates of infections,
      chronic GVHD, malignancy recurrence and 1-year TRM following immunosuppression
      with basiliximab were comparable with those found with other treatment modalities
      for aGVHD. We conclude that basiliximab is efficient and feasible for steroid
      refractory aGVHD and merits further evaluation.

PMID- 16098073
TI  - Impact of human leucocyte antigen mismatch on graft-versus-host disease and graft
      failure after reduced intensity conditioning allogeneic haematopoietic stem cell
      transplantation from related donors.
AB  - The impact of human leucocyte antigen (HLA) incompatibility between donor and
      recipient on graft-versus-host disease (GVHD) and graft failure after reduced
      intensity conditioning stem cell transplantation (RICT) remains to be elucidated.
      We retrospectively analysed outcome in 341 patients who underwent RICT from
      related donors for haematological malignancies. The overall cumulative incidence
      of grade II-IV acute GVHD (aGVHD) was 40% for all subjects; 39% in recipients
      with HLA-matched donors, 44% in those with one-locus-mismatched donors, and 50%
      in those with two- to three-loci-mismatched donors. In a Cox regression model
      adjusted for potential confounders, the tendency for grade II-IV aGVHD (P=0.01),
      chronic GVHD (cGVHD) (P=0.05) and graft failure (P=0.033) increased with HLA
      disparity. Use of peripheral blood grafts instead of marrow was a risk factor for
      cGVHD. Use of antithymocyte globulin was associated with reduced aGVHD and cGVHD.
      Overall survival (OS) in recipients of two- to three-loci-mismatched RICT at 2
      years (18%) was significantly worse than that in patients who received one-locus
      mismatched RICT (51%) and HLA-matched RICT (48%) (P<0.0001). A two- to three-loci
      mismatch was identified as an independent risk factor for OS (P<0.001), but there
      was no significant difference in OS between HLA-matched and one-locus-mismatched
      RICT. HLA incompatibility between the donor and recipient is an important risk
      factor for graft failure, aGVHD, cGVHD and OS after RICT. RICT from a one-locus
      mismatched donor may represent an effective alternative approach in patients with
      high-risk malignancies who lack HLA-matched related donors.

PMID- 16098074
TI  - High-dose idarubicin, cyclophosphamide and melphalan as conditioning for
      autologous stem cell transplantation increases treatment-related mortality in
      patients with multiple myeloma: results of a randomised study.
AB  - We conducted a randomised trial comparing an intensified versus a standard
      conditioning regimen for high-dose chemotherapy followed by autologous stem-cell
      transplantation in patients with multiple myeloma. In this study, 56 patients
      were randomly assigned for high-dose therapy with melphalan 200 mg/m2 or with
      idarubicin 42 mg/m2, melphalan 200 mg/m2 and cyclophosphamide 120 mg/kg. The
      primary objective was response rate. Acute toxicity, mainly because of
      infections, was higher in the intensified treatment arm with a treatment-related
      mortality of 20% versus 0% in the standard arm. This lead to the early
      discontinuation of the study. Response rates did not differ significantly between
      both treatment arms {intensified versus standard: complete response+near complete
      remission 50% [95% confidence interval (CI) 26-74%] vs. 33% (95% CI 17-55%),
      partial remission 35% (95% CI 16-61%) vs. 50% (95% CI 30-70%)}. After a follow-up
      of 5 years, the median time-to-progression and overall survival were not
      significantly different between both patient groups. Analysis restricted to
      patients surviving the first 100 d after transplant showed a better outcome for
      patients with >or=2 bad prognostic risk factors in the intensified treatment arm,
      however all treatment-related deaths occurred within this group of patients. In
      conclusion, intensified conditioning for high-dose therapy had intolerably high
      toxicity without improving outcome in patients with multiple myeloma.

PMID- 16098075
TI  - Improved outcome for children with disseminated adenoviral infection following
      allogeneic stem cell transplantation.
AB  - Adenovirus (AdV) infections are a frequent cause of morbidity and mortality
      following allogeneic stem cell transplantation (SCT), and disseminated infection
      is associated with high mortality, particularly in paediatric SCT. Here, we
      describe an approach to reduce mortality from adenoviraemia by combining
      prospective monitoring for the occurrence of adenoviraemia using a sensitive
      polymerase chain reaction method, early antiviral therapy and prompt withdrawal
      of immunosuppression. A total of 155 consecutive paediatric SCT procedures were
      prospectively monitored, of which 113 (73%) transplants involved donors other
      than matched siblings and 126 (83%) employed T-cell depletion. Adenoviraemia was
      detected in 26/155 (17%) transplants and developed exclusively in patients who
      had received T-cell-depleted grafts. Withdrawal of immunosuppression coupled with
      early antiviral therapy led to resolution of adenoviraemia in 19/26 (81%)
      patients with only five patients succumbing to disseminate AdV infection.
      Survival from adenoviraemia was associated with lymphocyte recovery to above
      0.3x10(9)/l. Mortality was closely linked with the absence of lymphocyte recovery
      because of profound T-cell depletion of the graft with CD34+ magnetic-activated
      cell sorting. Mortality from disseminated AdV infection was 5/26 (19%) in this
      study, which is significantly lower than previously reported.

PMID- 16098076
TI  - 188Re or 90Y-labelled anti-CD66 antibody as part of a dose-reduced conditioning
      regimen for patients with acute leukaemia or myelodysplastic syndrome over the
      age of 55: results of a phase I-II study.
AB  - In a phase I-II study for patients aged 55-65 years, we employed
      radioimmunotherapy using an anti-CD-66 antibody as part of a dose-reduced
      conditioning regimen, which was followed by a T-cell-depleted graft. 20 patients
      with a median age of 63 years suffering from acute leukaemia (n=17) or
      myelodysplastic syndrome (n=3) received the antibody labelled either with
      188Rhenium (n=8) or with 90Yttrium (n=12) during conditioning. Radioimmunotherapy
      provided a mean dose of 21.9 (+/-8.4) Gy to the bone marrow with a significantly
      higher dose when 90Yttrium was used. Additional conditioning was fludarabine
      based plus anti-thymocyte globulin in matched related donor transplants (n=11),
      or plus melphalan in matched unrelated donor transplants (n=9). Regimen-related
      toxicity was low, with two patients developing three episodes of grade III organ
      toxicity. All patients engrafted, grade II-IV acute graft-versus-host disease
      (GvHD) was observed in one patient (5%) and chronic GvHD in three patients (15%).
      The cumulative incidence of non-relapse mortality was 25%, the cumulative
      incidence of relapse 55%. The probability of survival was estimated to be 70% at
      1 year and 52% at 2 years post-transplant, although no plateau was reached
      afterwards. In conclusion, radioimmunotherapy using the anti-CD66 antibody was
      feasible and safe in our elderly patient group and provided a high marrow dose.

PMID- 16098077
TI  - C-reactive protein and D-dimer with clinical probability score in the exclusion
      of pulmonary embolism.
AB  - This study evaluated the diagnostic value of C-reactive protein (CRP) combined
      with a clinical decision rule in the exclusion of pulmonary embolism (PE) and
      compared this with D-dimer. In 363 consecutive outpatients CRP and D-dimer test
      were performed and clinical probability of PE was assessed. Patients with D-dimer
      levels<500 microg/l and clinical probability indicating 'PE unlikely' were
      followed for 3 months. Ventilation-perfusion scan or spiral computerized
      tomography was performed in patients with D-dimer levels>or=500 microg/l or
      clinical probability indicating 'PE likely'. The CRP had a sensitivity of 95.7%
      [95% confidence interval (CI): 90-100] and negative predictive value (NPV) of
      98.4% (96-100). CRP<5 mg/l with clinical probability score indicating 'PE
      unlikely' (n=108, 30%), had a sensitivity of 96.7% (90-100), a specificity of
      43.0% (37-49) and NPV of 99.1% (97-100). D-dimer<500 microg/l with clinical
      probability score indicating 'PE unlikely' (n=170, 51%), had a sensitivity of
      96.7% (90-100), a specificity of 67.9% (62-74) and NPV of 99.4% (98-100). Based
      on retrospective data it was concluded that a standard CRP test can potentially
      be used to safely exclude PE, either as a sole test or combined with clinical
      probability assessment. Prospective studies are needed to confirm these findings.

PMID- 16098078
TI  - Genotype-phenotype correlation in MYH9-related thrombocytopenia.
AB  - Mutation of the non-muscle myosin heavy chain type II-A results in MYH9-related
      hereditary macrothrombocytopenia (HMTC), including four autosomal dominant
      platelet disorders: May-Hegglin anomaly (MHA), Sebastian (SBS), Fechtner (FS) and
      Epstein (EPS) syndrome. Denaturing high-performance liquid chromatography (DHPLC)
      was optimised for rapid screening of the seven exons harbouring all but one of
      the previously reported mutations of MYH9. Individuals from 13 families with
      phenotypes suggestive of MYH9-related HMTC were screened for mutations by DHPLC
      followed by direct sequencing of samples with aberrant column retention time.
      Mutations were identified in all 13 families. Six distinct missense heterozygous
      mutations were found in 10 families, including six families with MHA or SBS
      (E1841K, D1424N), three families with FS (R702H, R1165C, and D1424Y), and one
      family with EPS (S96L). A truncating mutation (R1933X) was found in three MHA
      families. A review of all published mutations suggests that mutation in the C
      terminal coiled coil region or truncation of the tailpiece is associated with
      haematological-only phenotype, while mutation of the head ATPase domain
      frequently is associated with nephropathy and/or hearing loss. Mutations of other
      regions have intermediate expression of non-haematological characteristics.
      Further study is required to confirm these associations and understand the
      molecular basis for this genotype-phenotype relationship.

PMID- 16098079
TI  - Clinical and molecular variability in congenital dyserythropoietic anaemia type
      I.
AB  - Congenital dyserythropoietic anaemia (CDA) type I is a rare, inherited disorder
      characterised by ineffective erythropoiesis and macrocytic anaemia. Complex bone
      disease has only occasionally been associated with this disease. CDA I is caused
      by mutations in the CDAN1 gene encoding for codanin-1. Our aim was to
      characterise the CDAN1 mutation in eight unrelated patients with sporadic CDA I,
      three of whom had complex bone disease. Six novel mutations in the CDAN1 gene
      were identified. In two patients, one mutation and in another, both mutations
      were elusive. No patient was homozygous for a null-type mutation. However, one
      patient with complex bone disease was homozygous for a splice-site mutation (IVS
      12+5G>A). Western blotting revealed that codanin-1 synthesis was 65% less than
      the control. Five single nucleotide polymorphisms (SNPs) previously unreported in
      the literature or the SNP database were also identified. Although the absence of
      codanin-1 is probably lethal, the presence of 35% of the protein was compatible
      with life but was associated with severe clinical manifestations. However, in
      most patients studied, no correlation could be established between the expected
      levels of codanin-1 or the nature of the mutation and the severity of the
      clinical manifestations.

PMID- 16098080
TI  - Rapid and specific detection of clinically significant haemoglobinopathies using
      electrospray mass spectrometry-mass spectrometry.
AB  - Increasing demand for population screening for the haemoglobinopathies gives rise
      to a requirement for high throughput systems, which allow for cost effective,
      rapid, sensitive and specific screening of clinically significant haemoglobins.
      We have developed a practical and efficient approach using tryptic digestion and
      electrospray triple quadrupole mass spectrometry-mass spectrometry (MSMS) in
      multiple reaction monitoring acquisition mode for the identification of the
      clinically important haemoglobin variants, S, C, DPunjab, OArab, and E. A total
      of 200 blood samples, comprising 52 haemoglobin AA, 57 AS (sickle cell trait), 44
      AC (C trait), 16 SC (SC disease), 14 SS (sickle cell disease), 10 AE (E trait), 2
      ADPunjab (DPunjab trait) and 1 each of AOArab (OArab trait), CC (C disease),
      DPunjabDPunjab (DPunjab disease), OArabOArab (OArab disease), and EE (E disease),
      have been analysed in parallel with existing phenotype and molecular methods. All
      haemoglobin variants were correctly identified by MSMS, with no false positives
      or false negatives. The system detects both heterozygotes and homozygotes and has
      potential applications in neonatal and antenatal screening.

PMID- 16098081
TI  - Efficacy and tolerability of peginterferon alpha-2a with or without ribavirin in
      thalassaemia major patients with chronic hepatitis C virus infection.
AB  - Thalassaemia patients with genotype 1 or 4 chronic hepatitis C virus (HCV)
      infection were randomised to receive peginterferon alpha-2a 180 mg/week ribavirin
      for 48 weeks. Primary efficacy variable was sustained viral response (SVR) at 72
      weeks. Thirty-two patients were evaluated; 20 enrolled. Baseline characteristics
      were comparable. SVR occurred in four of 12 and five of eight patients in the
      monotherapy and combination groups (30% and 62.5%; P=0.19), respectively.
      Undetectable RNA at 12 weeks and age <18 years were associated with improved SVR
      (P<0.05). Transfusion requirements rose by 34% in the combination arm (P=0.08).
      Peginterferon/ribavirin was effective in thalassaemics with HCV and moderate iron
      overload.

PMID- 16098082
TI  - Absence of fibrinogen alpha-, beta- and gamma-chain mRNA in human platelets.

PMID- 16098083
TI  - Clustering and anticipation for nodular lymphocyte predominance Hodgkin lymphoma
      within a French Basque kindred.

PMID- 16098085
TI  - A proposed mechanism to explain the stimulatory effect of melatonin on
      antioxidative enzymes.
AB  - Melatonin, the main secretory product of the pineal gland, is known to
      collaborate against oxidative stress within cells, but its mechanism of action in
      terms of stimulating antioxidant enzymes remains unclear. Herein, we propose that
      melatonin modulates antioxidant enzyme activities via its interaction with
      calmodulin, which in turn inhibits downstream processes that lead to the
      inactivation of nuclear RORalpha melatonin receptor. Eventually, this nuclear
      transcription factor downregulates NF-kappaB-induced antioxidant enzyme
      expression. Therefore, the increment in antioxidant enzyme activities induced by
      melatonin involves the inhibition of the RORalpha pathway. Thus, in addition to
      its direct free radical scavenging activities, melatonin has important actions in
      oxidative defense by stimulating enzymes which metabolize free radicals and
      radical products to innocuous metabolites.

PMID- 16098086
TI  - Melatonin limits lung injury in bleomycin treated mice.
AB  - Melatonin is the principal secretory product of the pineal gland and its role as
      an immuno-modulator is well established. Recent evidence shows that melatonin is
      a scavenger of oxyradicals and peroxynitrite and exerts protective effects in
      septic shock, hemorrhagic shock and inflammation. The aim of this study was to
      investigate the effect of melatonin on the lung injury caused by bleomycin (BLM)
      administration. Mice subjected to intratracheal administration of BLM developed
      significant lung injury characterized by a marked neutrophil infiltration
      [assessed by myeloperoxidase (MPO) activity] and by tissue edema. In addition, an
      increase of immunoreactivity to nitrotyrosine, poly-ADP-ribose (PAR) was also
      observed in the lung of BLM-treated mice. Also, lung injury induced by BLM
      administration was correlated with a significant loss of body weight and with a
      significant mortality. Administration of melatonin (10 mg/kg i.p.) daily
      significantly reduced the (i) loss of body weight, (ii) mortality rate, (iii)
      infiltration of the lung with polymorphonuclear neutrophils (MPO activity), (iv)
      edema formation and (v) histological evidence of lung injury. Administration of
      melatonin also markedly reduced the nitrotyrosine and PAR formation. Taken
      together, our results demonstrate that treatment with melatonin significantly
      reduces lung injury induced by BLM in the mice.

PMID- 16098087
TI  - Effect of MT1 melatonin receptor deletion on melatonin-mediated phase shift of
      circadian rhythms in the C57BL/6 mouse.
AB  - In the mouse suprachiasmatic nucleus (SCN), melatonin activates MT1 and MT2 G
      protein coupled receptors, which are involved primarily in inhibition of neuronal
      firing and phase shift of circadian rhythms. This study investigated the ability
      of melatonin to phase shift circadian rhythms in wild type (WT) and MT1 melatonin
      receptor knockout (KO) C57BL/6 mice. In WT mice, melatonin (90 microg/mouse,
      s.c.) administered at circadian time 10 (CT10; CT12 onset of activity)
      significantly phase advanced the onset of the circadian activity rhythm (0.60 +/-
      0.09 hr, n = 41) when compared with vehicle treated controls (-0.02 +/- 0.07 hr,
      n = 28) (P < 0.001). In contrast, C57 MT1KO mice treated with melatonin did not
      phase shift circadian activity rhythms (-0.10 +/- 0.12 hr, n = 42) when compared
      with vehicle treated mice (-0.12 +/- 0.07 hr, n = 43). Similarly, in the C57
      MT1KO mouse melatonin did not accelerate re-entrainment to a new dark onset after
      an abrupt advance of the dark cycle. In contrast, melatonin (3 and 10 pm)
      significantly phase advanced circadian rhythm of neuronal firing in SCN brain
      slices independent of genotype with an identical maximal shift at 10 pm (C57 WT:
      3.61 +/- 0.38 hr, n = 3; C57 MT(1)KO: 3.45 +/- 0.11 hr, n = 4). Taken together,
      these results suggest that melatonin-mediated phase advances of circadian rhythms
      of neuronal firing in the SCN in vitro may involve activation of the MT2 receptor
      while in vivo activation of the MT1 and possibly the MT2 receptor may be
      necessary for the expression of melatonin-mediated phase shifts of overt
      circadian activity rhythms.

PMID- 16098088
TI  - Seasonal variations in the nycthemeral rhythm of plasma melatonin in the camel
      (Camelus dromedarius).
AB  - Seasonal changes in the pattern of plasma melatonin were investigated in two
      groups of camels (Camelus dromedarius): 11 adult and six young camels. Animals
      were subjected to the outdoor conditions of a desert environment. Blood samples
      were taken at regular intervals of about 3 hr (added to particular samples at 1
      hr before then 30 min and 1 hr after sunset, and 1 hr before and 1 hr after
      sunrise) for 24 hr at both solstices and equinoxes of the year. The plasma
      melatonin levels steeply increased soon after sunset and remained elevated
      throughout all the night. Then, melatonin concentrations progressively declined
      shortly before sunrise and returned to daytime basal levels 1 hr later. There was
      no seasonal variation in the amplitude or in the offset of the melatonin peak or
      in the daytime basal levels. The onset of the nocturnal peak was delayed by 2 hr
      in June at the summer solstice (P < 0.05), which can be related to the changes in
      night length between the two solstices. A significant effect of age was observed
      in all seasons. Melatonin levels were higher in the young camel group (fall
      equinox: P < 0.001; spring equinox: P < 0.01; winter solstice: P < 0.01; summer
      solstice: P < 0.05). The pattern of melatonin secretion in the camel showed a
      significant seasonal variation parallel to the photoperiodic changes of the year.
      The observed decline of melatonin levels during an extra-light pulse in the
      middle of the night indicates the light control of melatonin synthesis. It is not
      yet known if, in this low latitude desert region, the seasonal breeding period of
      the camel is cued by the photoperiod. The data obtained, however, clearly
      demonstrate that the camel has the capacity to follow and to integrate
      photoperiodic changes through melatonin changes.

PMID- 16098089
TI  - Melatonin reduces oxidative stress and increases gene expression in the cerebral
      cortex and cerebellum of aluminum-exposed rats.
AB  - The pro-oxidant activity of aluminum (Al), the protective role of exogenous
      melatonin, as well as the mRNA levels of some antioxidant enzymes, were
      determined in cortex and cerebellum of rats following exposure to Al and/or
      melatonin. Two groups of male rats received intraperitoneal injections of Al
      lactate or melatonin at doses of 7 mg Al/kg/day and 10 mg/kg/day, respectively,
      for 11 wk. A third group of animals received concurrently Al lactate (7 mg
      Al/kg/day) plus melatonin (10 mg/kg/day) during the same period. A fourth group
      of rats was used as control. At the end of the treatment, the cerebral cortex and
      cerebellum were removed and processed to examine the following oxidative stress
      markers: glutathione transferase (GST), reduced glutathione (GSH), oxidized
      glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase,
      glutathione peroxidase (GPx), catalase (CAT), thiobarbituric acid reactive
      substances (TBARS), as well as protein content. Moreover, gene expression of Cu
      ZnSOD, MnSOD, GPx and CAT was evaluated by real-time RT-PCR. On the other hand,
      Al, Fe, Mn, Cu and Zn concentrations were determined in cortex and cerebellum of
      rats. Oxidative stress was promoted in both neural regions following Al
      administration, resulting from the pro-oxidant activity related with an increase
      in tissue Al concentrations. In contrast, melatonin exerted an antioxidant action
      which was related with an increase in the mRNA levels of the antioxidant enzymes
      evaluated. The results of the present investigation emphasize the potential use
      of melatonin as a supplement in the therapy of neurological disorders in which
      oxidative stress is involved.

PMID- 16098090
TI  - Melatonin acts as a growth-stimulating compound in some monocot species.
AB  - In a recent study melatonin (N-acetyl-5-methoxytryptamine), a well-investigated
      animal molecule but minimally studied in plants, was seen to have a physiological
      role as growth-promoting molecule in lupin hypocotyls. In the present study, the
      role of melatonin as a growth promoter is extended to coleoptiles of canary
      grass, wheat, barley and oat, in which it shows a relative auxinic activity [with
      respect to indole-3-acetic acid (IAA), the main auxin in plants] of between 10
      and 55%. In addition, melatonin is seen to have an important inhibitory growth
      effect on roots similar to that played by auxin. The quantitation by liquid
      chromatography with electrochemical detection and identification by tandem mass
      spectrometry of melatonin and IAA in etiolated coleoptiles of the monocots
      assayed showed that both compounds are present in similar levels in these
      tissues. These results point to the co-existence of auxin and melatonin in
      tissues and raises the possibility of their co-participation in some
      physiological actions as auxinic hormones in plants.

PMID- 16098091
TI  - Melatonin prevents experimental liver cirrhosis induced by thioacetamide in rats.
AB  - Liver cirrhosis is a critical stage of chronic liver diseases that can produce
      liver failure, portal hypertension and hepatocarcinoma. Sustained oxidative
      stress plays a key role in cell damage and fibrosis induced during liver
      cirrhosis. We evaluated the effect of oxidative stress regulation by melatonin on
      the development of parenchymal destruction and stellate cell activation in
      experimental liver cirrhosis. Melatonin was administered to rats with liver
      cirrhosis induced by thioacetamide (TAA) for 1 or 3 months. Liver injury was
      assessed by serological analysis, as well as hematoxylin-eosin staining and the
      in situ apoptosis detection assay in liver sections. Oxidative stress was
      evaluated by lipoperoxide and reduced glutathione levels, and by the measurement
      of catalase and superoxide dismutase activities in liver and serum respectively.
      The activation of stellate cells was evaluated by alpha-smooth muscle actin
      expression in liver sections. Our results showed that TAA induced oxidative
      stress with extensive tissue damage and enhanced alpha-smooth muscle actin
      expression in liver. Melatonin prevented the oxidative stress-related changes
      associated with TAA toxicity. In conclusion, the study showed that melatonin
      prevents the tissue damage and fibrosis associated with TAA-induced liver
      cirrhosis in rats.

PMID- 16098092
TI  - Tissue-plasminogen activator-induced ischemic brain injury is reversed by
      melatonin: role of iNOS and Akt.
AB  - In vivo studies showed that tissue-plasminogen activator (t-PA) may aggravate
      neuronal injury after focal cerebral ischemia. We hypothesized that t-PA impairs
      survival-promoting cell signaling in the ischemic brain, which may be reversed by
      a neuroprotectant, i.e. melatonin. We examined the effects of t-PA (10 mg/kg,
      i.v.), administered alone or in combination with melatonin (4 mg/kg, i.p.), on
      ischemic injury, inducible nitric oxide synthase (iNOS) expression as well as
      Akt, Bcl-X(L) and caspase-3 signaling following 90 min of intraluminal middle
      cerebral artery (MCA) occlusion in mice. t-PA, delivered immediately after
      reperfusion onset, increased infarct volume at 24 hr after MCA occlusion, in
      accordance with previous findings. Melatonin reduced infarct size when
      administered alone and reversed the t-PA-induced brain injury.
      Immunohistochemical studies showed that t-PA treatment was associated with an
      accumulation of iNOS positive cells in ischemic brain areas, which was abolished
      after co-delivery of melatonin. Western blots revealed that t-PA decreased
      phosphorylated Akt levels, but did not influence Bcl-X(L) expression and caspase
      3 activity in ischemic brain lysates. Co-treatment with melatonin restored
      phosphorylated Akt levels, increased Bcl-X(L) expression and reduced caspase-3
      activity. We provide evidence that t-PA-induced brain injury is accompanied by an
      activation of iNOS and inhibition of phosphatidylinositol-3 kinase/Akt. That
      melatonin reversed these signaling changes and the t-PA-induced brain injury
      makes this indole attractive as an add-on treatment with thrombolytics.

PMID- 16098093
TI  - Melatonin-selenium nanoparticles inhibit oxidative stress and protect against
      hepatic injury induced by Bacillus Calmette-Guerin/lipopolysaccharide in mice.
AB  - Melatonin-selenium nanoparticles (MT-Se), a novel complex, were synthesized by
      preparing selenium nanoparticles in melatonin medium. The present investigation
      was designed to determine the protective effects of MT-Se against Bacillus
      Calmette-Guerin (BCG)/lipopolysaccharide (LPS)-induced hepatic injury in mice. In
      BCG/LPS-induced hepatic injury model, MT-Se administered (i.g.) at doses of 5,
      10, or 20 mg/kg to BCG/LPS-treated mice for 10 days, significantly reduced the
      increase in plasma aminotransferase, reduced the severe extent of hepatic cell
      damage and the immigration of inflammatory cells. The MT-Se particles also
      attenuated the increase in the content of thiobarbituric acid-reactive substances
      and enhanced the decrease in reduced activities of superoxide dismutase and
      glutathione peroxidase (GPx). However, treatment with MT-Se suppressed the
      increase in nitric oxide levels both in plasma and liver tissue. Furthermore,
      supplementation with MT-Se at the dose of 10 mg/kg (composed of 9.9 mg/kg
      melatonin and 0.1 mg/kg selenium) had great capability to protect against
      hepatocellular damage than a similar dose of melatonin (10 mg/kg) or selenium
      (0.1 mg/kg) alone. This effect may relate to its higher antioxidant efficacy in
      decreasing lipid peroxidation and increasing GPx activity. These results suggest
      that the mode of MT-Se hepatic protective action is, at least in part, related to
      its antioxidant properties.

PMID- 16098094
TI  - Protective effect of melatonin on ascorbate-Fe2+ lipid peroxidation of
      polyunsaturated fatty acids in rat liver, kidney and brain microsomes: a
      chemiluminescence study.
AB  - Melatonin (N-acetyl-5-methoxytryptamine), the main secretory product of the
      pineal gland, is a free radical scavenger that has been found to protect against
      lipid peroxidation in many experimental models. In the present study the effect
      of melatonin on lipid peroxidation of long chain polyunsaturated fatty acids
      located in rat liver, kidney and brain microsomes was determined using gas
      chromatography and a chemiluminescence assay. In vitro assays showed that after
      incubation of rat liver, kidney or brain microsomes in an ascorbate-Fe++ system,
      at 37 degrees C for 180 min, the total cpm originated from light emission
      (chemiluminescence) was found to be lower in those membranes incubated in the
      presence of melatonin. The incubation of rat liver, kidney or brain microsomes in
      the presence of ascorbate-Fe2+ resulted in lipid-peroxidation of membranes as
      evidenced by light emission and decrease of docosahexaenoic acid 22:6 n-3 and
      arachidonic acid 20:4 n-6. In the presence of melatonin (0.5, 1.0, 1.5 mm), light
      emission percent inhibition of microsomes was: (liver - 3.33, 9.98, 39.40)
      (kidney - 46.79, 61.88, 68.36) and (brain - 33.36, 28.89, 43.32). Not all fatty
      acids were equally protected after the addition of melatonin to the incubation
      medium. Our results indicate a selective protection of C20:4 n6 and C22:6 n3 by
      melatonin during non-enzymatic lipid peroxidation of rat liver, kidney and brain
      microsomes.

PMID- 16098095
TI  - The antidepressant-like effect of the melatonin receptor ligand luzindole in mice
      during forced swimming requires expression of MT2 but not MT1 melatonin
      receptors.
AB  - We previously reported an antidepressant-like effect in C3H/HeN mice during the
      forced swimming test (FST) following treatment with the MT1/MT2 melatonin
      receptor ligand, luzindole. This study investigated the role melatonin receptors
      (MT1 and/or MT2) may play in the effect of luzindole in the FST using C3H/HeN
      mice with a genetic deletion of either MT1 (MT1KO) or MT2 (MT2KO) melatonin
      receptors. In the light phase (ZT 9-11), luzindole (30 mg/kg, i.p.) significantly
      decreased immobility during swimming in both wild type (WT) (135.6 +/- 25.3 s, n
      = 7) and MT(1)KO (132.6 +/- 13.3 s, n = 8) as compared with vehicle-treated mice
      (WT: 207.1 +/- 6.0 s, n = 7; MT1KO: 209.5 +/- 6.2 s, n = 8) (P < 0.001). In the
      dark phase (ZT 20-22), luzindole also decreased time of immobility in both WT
      (89.5 +/- 13.9 s, n = 8) and MT1KO (66.5 +/- 6.4 s, n = 8) mice as compared with
      the vehicle treated (WT: 193.8 +/- 3.5, n = 6; MT1KO: 176.6 +/- 6.2 s, n = 8) (P
      < 0.001). Genetic disruption of the MT1 gene did not alter the diurnal rhythm of
      serum melatonin in MT1KO mice (ZT 9-11: 1.3 +/- 0.6 pg/mL, n = 7; ZT 20-22: 10.3
      +/- 1.1 pg/mL, n = 8) as compared with WT (ZT 9-11: 1.4 +/- 0.7 pg/mL; ZT 20-22:
      10.6 pg/mL). Swimming did not alter the serum melatonin diurnal rhythm in WT and
      MT1KO mice. Decreases in immobility of WT and MT1KO mice by luzindole treatment
      were not affected by gender or age (3 months versus 8 months). In contrast,
      luzindole did not decrease immobility during the FST in MT2KO mice. We conclude
      that the antidepressant-like effect of luzindole may be mediated through blockade
      of MT2 rather than MT1 melatonin receptors.

PMID- 16098096
TI  - Reduced lipolysis and increased lipogenesis in adipose tissue from
      pinealectomized rats adapted to training.
AB  - The current study investigated the effects of chronic training and pinealectomy
      on the lipogenic and lipolytic activity of adipose tissue. Pinealectomized and
      sham-operated adult male Wistar rats were distributed in to four subgroups:
      pinealectomized untrained, pinealectomized trained, control untrained and control
      trained. At the end of the training period (8 wk) the rats were killed. Blood
      samples were collected for glucose, insulin and leptin determinations. Peri
      epididymal adipocytes were isolated for measurement of in vitro rates of
      lipolysis and incorporation of substrates (D-[U-14C]-glucose, L-[U-14C]-lactate,
      [2-14C]-acetate and [1-14C]-palmitate) into lipids, and samples of epididymal
      adipose tissue were homogenized for evaluation of glucose-6-phosphate
      dehydrogenase maximal activity. Pinealectomy resulted in a significantly
      increased lipolytic capacity in response to isoproterenol and a decrease in
      circulating leptin levels without affecting the rates of incorporation of
      different substrates into lipids. However, only in the intact control group did
      training promote a higher basal and isoproterenol-stimulated lipolysis, increase
      the incorporation of palmitate (esterification), decrease the incorporation of
      acetate (lipogenesis) into lipids and diminish circulating leptin levels. These
      effects of exercise training were not seen in pinealectomized rats. However,
      pinealectomized trained animals showed a marked reduction in lipolysis and an
      increased rate of acetate incorporation. In conclusion, we demonstrated for the
      first time that the pineal gland plays an important role in the regulation of
      lipid metabolism in such a way that its absence caused a severe alteration in the
      balance between lipogenesis and lipolysis, which becomes evident with the
      adaptation to exercise training.

PMID- 16098097
TI  - Interactions between melatonin and nicotinamide nucleotide: NADH preservation in
      cells and in cell-free systems by melatonin.
AB  - Interactions of melatonin and nicotinamide adenine dinucleotide (NADH) have been
      studied in different experimental models including NADH-promoted oxyhemoglobin
      oxidation, vanadate-induced NADH oxidation and paraquat-induced NADH depletion in
      cultured PC12 cells. Our findings indicate that melatonin preserves NADH levels
      under oxidative stress both in cell-free systems and in cultured PC12 cells.
      These interactions likely involve electron donation by melatonin and reduction of
      the NAD radical. As a result, the NAD radical is recycled to NADH and melatonin
      is oxidized to N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK). NADH is a central
      molecule at the crossroads between energy metabolism and the antioxidant defense
      system in organisms. Recycling of NADH by melatonin might improve the efficiency
      of NADH as an energy carrier and as an antioxidant. Interactions between
      melatonin and NADH may be implicated in mitochondrial metabolism.

PMID- 16098098
TI  - Circadian phase determined from melatonin profiles is reproducible after 1 wk in
      subjects who sleep later on weekends.
AB  - The aim of this study was to determine whether circadian phase from salivary
      melatonin profiles is the same when measured in phase assessments 1 wk apart.
      Eleven healthy young men and women maintained a fixed, home sleep-wake schedule,
      in bed, in the dark 23:00-07:00 hr on weekdays. On Friday and Saturday nights
      they were permitted to wake up and go to bed up to 1 hr later, and on Saturdays
      and Sundays they could nap between 13:30 and 16:30 hr. The study was run in the
      summer. Subjects wore sunglasses when outside during the day, and went outside
      for at least 15 min between 08:00 and 09:00 hr each morning. They maintained this
      schedule for 15 days before the first assessment and the 6 days in between the
      two assessments. During the assessments subjects remained awake overnight in <5
      lux and gave saliva samples every 30 min. A recovery nap (13:00-17:00 hr)
      followed the first session. The dim light melatonin onset (DLMO), offset (DLMOff)
      and midpoint were used as phase markers. There was minimal change in their timing
      between the two phase assessments. The average absolute change in midpoint (the
      change in phase regardless of direction) was 20 min. There was a small, 30 min
      delay in the DLMO. Thus, circadian phase can be measured a week in advance of any
      phase shifting intervention and, as long as the prescribed sleep and morning
      light schedule is maintained, the phase at the start of treatment can be
      confidently estimated.

PMID- 16098099
TI  - Positive relationship between melatonin receptor type 1B polymorphism and
      rheumatoid factor in rheumatoid arthritis patients in the Korean population.
AB  - Melatonin is reported to be an anti-inflammatory agent. No genetic study
      concerning the association between melatonin and inflammatory disease has yet
      been reported. Here we performed a polymorphism study on the melatonin receptor
      type 1B (MTNR1B) in Korean rheumatoid arthritis (RA) patients and controls. The
      polymorphism of MTNR1B located in 3'-untranslated region (rs 1562444) was
      selected for its higher rate of heterozygosity among other single nucleotide
      polymorphisms (SNPs) in both MTNR1A and MTNR1B genes and investigated in RA
      patients (n = 173) and healthy controls (n = 195) by polymerase chain reaction
      restriction fragment length polymorphism assay using NlaIII restriction enzyme.
      No statistically significant difference in either genotype distribution or allele
      frequency was observed between RA patients and controls. The genotype
      distributions and allele frequencies of rheumatoid factor negative [RF(-)]
      patients were similar to those of controls. However, statistical analysis of
      genotype revealed a significant association (chi2 = 6.42, P = 0.04) is present
      between RF(+) and MTNR1B SNP (rs 1562444). Although no statistically significant
      difference in allele frequency between RF(+) and controls was observed (chi2 =
      2.75, P = 0.10), the results might suggest that MTNR1B SNP (rs 1562444) is
      associated with the presence of RF in RA. This is the first study, to our
      knowledge, to report a positive genetic relationship between melatonin and RA.

PMID- 16098100
TI  - Melatonin restores the cytochrome oxidase reactivity in the nodose ganglia of
      acute hypoxic rats.
AB  - This study aimed to elucidate whether melatonin would exert beneficial effects on
      the neuronal functions of the nodose ganglion (NG) following acute hypoxic
      insult. The cytochrome oxidase (COX) and the nicotinamine adenine dinucleotide
      phosphate diaphorase (NADPH-d) histochemistry along with the nitric oxide
      synthase (NOS) immunofluorescence were used to examine the metabolic stage and
      nitric oxide production in nodose neurons respectively. Adult rats were injected
      intraperitoneally with melatonin at 5 or 100 mg/kg. Hypoxia was achieved by
      placing the rats into an altitude chamber (PO2 = 43 torr) for 4 hr. The results
      show that in normal untreated rats, nearly all and about 43% of the NG neurons
      displayed COX and NOS/NADPH-d reactivities with various staining intensities
      respectively. However, COX reactivity was drastically decreased while NOS/NADPH-d
      reactivity was significantly upregulated following hypoxia treatment. In
      melatonin pretreated rats, the hypoxia-induced reduction of COX reactivity was
      obviously prevented and the augmentation of NOS/NADPH-d reactivity was
      successfully suppressed. The deficit in the metabolic stage and the over
      activation of NOS would contribute to the generation of oxidative stress. By
      effectively preventing the metabolic disruption, melatonin may have potential
      utility in therapeutic treatment of neuronal dysfunctions where oxidative stress
      is a participant.

PMID- 16098101
TI  - Melatonin as an antioxidant: physiology versus pharmacology.

PMID- 16098102
TI  - Modulated targeting of GFP-AtMAP65-1 to central spindle microtubules during
      division.
AB  - AtMAP65-1 bundles cortical microtubules and we examined how this property is
      regulated during division in time-lapse studies of Arabidopsis suspension cells
      expressing GFP-AtMAP65-1. Spindle fluorescence is diffuse during metaphase,
      restored to the central spindle at anaphase and then compacted at the midline
      during late anaphase/early telophase. However, mutagenesis of the microtubule
      associated protein (MAP) consensus Cdk site to a non-phosphorylatable form allows
      premature decoration of microtubules traversing the central region of the
      metaphase spindle without affecting the timing of the subsequent compaction. This
      suggests that mutagenesis does not affect compaction but does affect a
      phosphorylation/dephosphorylation switch that normally targets AtMAP65-1 to the
      central spindle at the metaphase/anaphase transition. GFP-AtMAP65-1 continues to
      label the midline of the early phragmoplast, suggesting a structural continuity
      with the central spindle - both structures being composed of anti-parallel
      microtubules. However, once the cytokinetic apparatus expands into a ring the MAP
      becomes depleted at the midline. Despite this, cytokinesis is not arrested and
      membrane and callose are deposited at the cell plate. It is concluded that
      AtMAP65-1 plays a role in the central spindle at anaphase to early cytokinesis
      but is not essential at the midline of the phragmoplast at later stages.

PMID- 16098103
TI  - Involvement of SRD2-mediated activation of snRNA transcription in the control of
      cell proliferation competence in Arabidopsis.
AB  - The transcription machinery of small nuclear RNA (snRNA) genes has been
      investigated extensively in human cell-free systems, but its physiological
      function in vivo has not been addressed. This paper demonstrates the
      physiological role of an activator of snRNA transcription using a temperature
      sensitive mutant of Arabidopsis thaliana, srd2. Phenotypic characteristics of the
      srd2 mutant suggest that the SRD2 gene participates in the control of competence
      in cell proliferation. The SRD2 gene encodes a nuclear protein that shares
      sequence similarity with the human SNAP50 protein, which is a subunit of SNAPc
      and is required for snRNA transcription in vitro. Our results, obtained from
      analysis of snRNA expression in the srd2 mutant, indicate that the SRD2 protein
      functions in the upregulation of transcription of snRNA genes, the promoters of
      which contain the upstream sequence element, to elevate cell proliferation
      competence.

PMID- 16098104
TI  - High-throughput in planta expression screening identifies a class II ethylene
      responsive element binding factor-like protein that regulates plant cell death
      and non-host resistance.
AB  - We performed high-throughput screening using the potato virus X (PVX) system to
      overexpress Nicotiana benthamiana genes in planta and identify positive
      regulators of cell death. This screening identified NbCD1, a novel class II
      ethylene-responsive element binding factor (ERF), as a potent inducer of the
      hypersensitive response (HR)-like cell death. NbCD1 expression was induced by
      treatments with INF1 elicitor and a non-host pathogen Pseudomonas cichorii. NbCD1
      exhibited transcriptional repressor activity through its EAR motif, and this
      motif was necessary for NbCD1 to cause cell death. We identified 58 genes that
      displayed altered transcription following NbCD1 overexpression. NbCD1
      overexpression downregulated the expression of HSR203, a negative regulator of
      hypersensitive death. Conditional expression of NbCD1 in Arabidopsis also caused
      cell death, indicating that NbCD1 downstream cascades are conserved in dicot
      plants. To further confirm the role of NbCD1 in defense, we used virus-induced
      gene silencing to demonstrate that NbCD1 is required for non-host resistance of
      N. benthamiana to the bacterial pathogen P. cichorii. Our data point to a model
      of transcriptional regulatory cascades. NbCD1 positively regulates cell death and
      contributes to non-host resistance, possibly by downregulating the expression of
      other defense response genes.

PMID- 16098105
TI  - Sugar and ABA responsiveness of a minimal RBCS light-responsive unit is mediated
      by direct binding of ABI4.
AB  - Photosynthesis-associated nuclear genes (PhANGs) are able to respond to multiple
      environmental and developmental signals, including light, sugars and abscisic
      acid (ABA). PhANGs have been extensively studied at the level of transcriptional
      regulation and several cis-acting elements important for light responsiveness
      have been identified in their promoter sequences. However, the regulatory
      elements involved in sugar and ABA regulation of PhANGs have not been completely
      characterized. Using conserved modular arrangement 5 (CMA5), a previously
      characterized minimal light-responsive unit, we show that in Arabidopsis thaliana
      this unit responds not only positively to light signals, but also negatively to
      sugars and ABA. The latter responses were found to be impaired in the abi4
      mutant, indicating that ABSCISIC ACID INSENSITIVE-4 (ABI4) is a regulator
      involved in sugar and ABA repression of this minimal regulatory unit.
      Furthermore, we report a new sequence element conserved in several rbcS
      promoters, herewith named S-box, which is important for the sugar and ABA
      responsiveness of CMA5. This sequence corresponds to a putative ABI4-binding
      site, which is in fact bound by the Arabidopsis ABI4 protein in vitro. The S-box
      is closely associated with the G-box present in CMA5, and this association is
      conserved in the promoters of several RBCS genes. This phylogenetically conserved
      promoter feature probably reflects a common regulatory mechanism and identifies a
      point of convergence between light- and sugar-signaling pathways.

PMID- 16098106
TI  - Protein phosphorylation is a prerequisite for intracellular Ca2+ release and ion
      channel control by nitric oxide and abscisic acid in guard cells.
AB  - Recent work has indicated that nitric oxide (NO) and its synthesis are important
      elements of signal cascades in plant-pathogen defence, and are a prerequisite for
      drought and abscisic acid (ABA) responses in Arabidopsis thaliana and Vicia faba
      guard cells. NO regulates inward-rectifying K+ channels and Cl- channels of Vicia
      guard cells via intracellular Ca2+ release. However, its integration with related
      signals, including the actions of serine-threonine protein kinases, is less well
      defined. We report here that the elevation of cytosolic-free [Ca2+] ([Ca2+]i)
      mediated by NO in guard cells is reversibly inhibited by the broad-range protein
      kinase antagonists staurosporine and K252A, but not by the tyrosine kinase
      antagonist genistein. The effects of kinase antagonism translate directly to a
      loss of NO-sensitivity of the inward-rectifying K+ channels and background (Cl-
      channel) current, and to a parallel loss in sensitivity of the K+ channels to
      ABA. These results demonstrate that NO-dependent signals can be modulated through
      protein phosphorylation upstream of intracellular Ca2+ release, and they
      implicate a target for protein kinase control in ABA signalling that feeds into
      NO-dependent Ca2+ release.

PMID- 16098107
TI  - UPF3 suppresses aberrant spliced mRNA in Arabidopsis.
AB  - It has been reported that eukaryotic organisms have a nonsense-mediated mRNA
      decay (NMD) system to exclude aberrant mRNAs that produce truncated proteins. NMD
      is an RNA surveillance pathway that degrades mRNAs possessing premature
      translation termination codons (PTCs), thus avoiding production of possibly toxic
      truncated proteins. Three interacting proteins, UPF1, UPF2 and UPF3, are required
      for NMD in mammals and yeasts, and their amino acid sequences are well conserved
      among most eukaryotes, including plants. In this study, 'The Arabidopsis
      Information Resource' database was searched for mRNAs with premature termination
      codons. We selected five of these mRNAs and checked for the presence of PTCs in
      these mRNAs when translated in vivo. As a result we identified aberrant mRNAs
      produced by alternative splicing for each gene. These genes produced at least one
      alternative splicing variant including a PTC (PTC+) and another variant without a
      PTC (PTC-). We analyzed their PTC+/PTC- ratios in wild-type Arabidopsis and upf3
      mutant plants and showed that the PTC+/PTC- ratios were higher in atupf3 mutant
      plants than wild-type plants and that the atupf3 mutant was less able to degrade
      mRNAs with premature termination codons than wild-type plants. This indicated
      that the AtUPF3 gene is required by the plant NMD system to obviate aberrantly
      spliced mRNA.

PMID- 16098108
TI  - Light and plastid signals regulate the expression of the pea plastocyanin gene
      through a common region at the 5' end of the coding region.
AB  - Expression of the pea plastocyanin gene (PetE) is regulated by light and plastid
      signals. Previous work indicated that light and plastid regulation of pea PetE
      operates post-transcriptionally in transgenic tobacco, and requires the correct
      5' terminus of the PetE transcript and the PetE-coding region. The post
      transcriptional light and plastid regulation of pea PetE has now been
      demonstrated to operate in transgenic Arabidopsis, where in contrast the
      endogenous PETE gene is regulated transcriptionally. Transgenic tobacco seedlings
      containing constructs with progressive 3' deletions of the PetE-coding region
      fused to the luciferase (Luc) reporter gene demonstrate that the first 60
      nucleotides of the coding region are sufficient for regulated accumulation of Luc
      transcripts by light and plastid signalling pathways affected by treatment with
      norflurazon and lincomycin. PetE constructs containing premature stop codons were
      generated to investigate whether translation has a role in light or plastid
      regulation. Insertion of a stop codon in place of the second codon of the PetE
      coding region diminished both light and plastid regulation of PetE transcripts,
      whereas stop codons inserted later in the transcript had no effect on light or
      plastid regulation. These experiments indicate that the 5' end of the
      plastocyanin-coding region contains sequences important for regulation by light
      and plastid signals.

PMID- 16098109
TI  - EgMYB2, a new transcriptional activator from Eucalyptus xylem, regulates
      secondary cell wall formation and lignin biosynthesis.
AB  - Summary EgMYB2, a member of a new subgroup of the R2R3 MYB family of
      transcription factors, was cloned from a library consisting of RNA from
      differentiating Eucalyptus xylem. EgMYB2 maps to a unique locus on the Eucalyptus
      grandis linkage map and co-localizes with a quantitative trait locus (QTL) for
      lignin content. Recombinant EgMYB2 protein was able to bind specifically the cis
      regulatory regions of the promoters of two lignin biosynthetic genes, cinnamoyl
      coenzyme A reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD), which
      contain MYB consensus binding sites. EgMYB2 was also able to regulate their
      transcription in both transient and stable expression assays. Transgenic tobacco
      plants over-expressing EgMYB2 displayed phenotypic changes relative to wild-type
      plants, among which were a dramatic increase in secondary cell wall thickness,
      and an alteration of the lignin profiles. Transcript abundance of genes encoding
      enzymes specific to lignin biosynthesis was increased to varying extents
      according to the position of individual genes in the pathway, whereas core
      phenylpropanoid genes were not significantly affected. Together these results
      suggest a role for EgMYB2 in the co-ordinated control of genes belonging to the
      monolignol-specific pathway, and therefore in the biosynthesis of lignin and the
      regulation of secondary cell wall formation.

PMID- 16098110
TI  - Identification, subcellular localization and biochemical characterization of
      water-soluble heteroglycans (SHG) in leaves of Arabidopsis thaliana L.: distinct
      SHG reside in the cytosol and in the apoplast.
AB  - Water-soluble heteroglycans (SHG) were isolated from leaves of wild-type
      Arabidopsis thaliana L. and from two starch-deficient mutants. Major constituents
      of the SHG are arabinose, galactose, rhamnose, and glucose. SHG was separated
      into low (<10 kDa; SHG(S)) and high (>10 kDa; SHG(L)) molecular weight compounds.
      SHG(S) was resolved into approximately 25 distinct oligoglycans by ion exchange
      chromatography. SHG(L) was further separated into two subfractions, designated as
      subfraction I and II, by field flow fractionation. For the intracellular
      localization of the various SHG compounds several approaches were chosen: first,
      leaf material was subjected to non-aqueous fractionation. The apolar gradient
      fractions were characterized by monitoring markers and were used as starting
      material for the SHG isolation. Subfraction I and SHG(S) exhibited a distribution
      similar to that of cytosolic markers whereas subfraction II cofractionated with
      crystalline cellulose. Secondly, intact organelles were isolated and used for SHG
      isolation. Preparations of intact organelles (mitochondria plus peroxisomes)
      contained no significant amount of any heteroglycan. In isolated intact
      microsomes a series of oligoglycans was recovered but neither subfraction I nor
      II. In in vitro assays using glucose 1-phosphate and recombinant cytosolic (Pho
      2) phosphorylase both SHG(S) and subfraction I acted as glucosyl acceptor whereas
      subfraction II was essentially inactive. Rabbit muscle phosphorylase a did not
      utilize any of the plant glycans indicating a specific Pho 2-glycan interaction.
      As revealed by in vivo labeling experiments using 14CO2 carbon fluxes into
      subfraction I and II differed. Furthermore, in leaves the pool size of
      subfraction I varied during the light-dark regime.

PMID- 16098111
TI  - A new role of the Arabidopsis SEPALLATA3 gene revealed by its constitutive
      expression.
AB  - During Arabidopsis flower development a set of homeotic genes plays a central
      role in specifying the distinct floral organs of the four whorls, sepals in the
      outermost whorl, and petals, stamens, and carpels in the sequentially inner
      whorls. The current model for the identity of the floral organs includes the
      SEPALLATA genes that act in combination with the A, B and C genes for the
      specification of sepals, petals, stamens and carpels. According to this new
      model, the floral organ identity proteins would form different complexes of
      proteins for the activation of the downstream genes. We show that the presence of
      SEPALLATA proteins is needed to activate the AG downstream gene SHATTERPROOF2,
      and that SEPALLATA4 alone does not provide with enough SEPALLATA activity for the
      complex to be functional. Our results suggest that CAULIFLOWER may be part of the
      protein complex responsible for petal development and that it is fully required
      in the absence of APETALA1 in 35S::SEP3 plants. In addition, genetic and
      molecular experiments using plants constitutively expressing SEPALLATA3 revealed
      a new role of SEPALLATA3 in activating other B and C function genes. We
      molecularly prove that the ectopic expression of SEPALLATA3 is sufficient to
      ectopically activate APETALA3 and AGAMOUS. Remarkably, plants that constitutively
      express both SEPALLATA3 and LEAFY developed ectopic petals, carpels and ovules
      outside of the floral context.

PMID- 16098112
TI  - Ethylene regulates fast apoplastic acidification and expansin A transcription
      during submergence-induced petiole elongation in Rumex palustris.
AB  - The semi-aquatic dicot Rumex palustris responds to complete submergence by
      enhanced elongation of young petioles. This elongation of petiole cells brings
      leaf blades above the water surface, thus reinstating gas exchange with the
      atmosphere and increasing survival in flood-prone environments. We already know
      that an enhanced internal level of the gaseous hormone ethylene is the primary
      signal for underwater escape in R. palustris. Further downstream, concentration
      changes in abscisic acid (ABA), gibberellin (GA) and auxin are required to gain
      fast cell elongation under water. A prerequisite for cell elongation in general
      is cell wall loosening mediated by proteins such as expansins. Expansin genes
      might, therefore, be important target genes in submergence-induced and plant
      hormone-mediated petiole elongation. To test this hypothesis we have studied the
      identity, kinetics and regulation of expansin A mRNA abundance and protein
      activity, as well as examined pH changes in cell walls associated with this
      adaptive growth. We found a novel role of ethylene in triggering two processes
      affecting cell wall loosening during submergence-induced petiole elongation.
      First, ethylene was shown to promote fast net H(+) extrusion, leading to
      apoplastic acidification. Secondly, ethylene upregulates one expansin A gene
      (RpEXPA1), as measured with real-time RT-PCR, out of a group of 13 R. palustris
      expansin A genes tested. Furthermore, a significant accumulation of expansin
      proteins belonging to the same size class as RpEXPA1, as well as a strong
      increase in expansin activity, were apparent within 4-6 h of submergence.
      Regulation of RpEXPA1 transcript levels depends on ethylene action and not on GA
      and ABA, demonstrating that ethylene evokes at least three, parallel operating
      pathways that, when integrated at the whole petiole level, lead to coordinated
      underwater elongation. The first pathway involves ethylene-modulated changes in
      ABA and GA, these acting on as yet unknown downstream components, whereas the
      second and third routes encompass ethylene-induced apoplastic acidification and
      ethylene-induced RpEXPA1 upregulation.

PMID- 16098113
TI  - Tiling array-driven elucidation of transcriptional structures based on maximum
      likelihood and Markov models.
AB  - Tiling arrays of high-density oligonucleotide probes spanning the entire genome
      are powerful tools for the discovery of new genes. However, it is difficult to
      determine the structure of the spliced product of a structurally unknown gene
      from noisy array signals only. Here we introduce a statistical method that
      estimates the precise splicing points and the exon/intron structure of a
      structurally unknown gene by maximizing the odds or the ratio of posterior
      probabilities of the structure under the observation of array signal intensities
      and nucleic acid sequences. Our method more accurately predicted the gene
      structures than the simple threshold-based method, and more correctly estimated
      the expression values of structurally unknown genes than the window-based method.
      It was observed that the Markov model contributed to the precision of splice
      points, and that the statistical significance of expression (P-value) represented
      the reliability of the estimated gene structure and expression value well. We
      have implemented the method as a program ARTADE (ARabidopsis Tiling Array-based
      Detection of Exons) and applied it to the Arabidopsis thaliana whole-genome array
      data analysis. The database of the predicted results and the ARTADE program are
      available at http://omicspace.riken.jp/ARTADE/.

PMID- 16098115
TI  - The experiences of and the nursing care for breast cancer patients undergoing
      immediate breast reconstruction.
AB  - This study explores the experiences of and the nursing care for nine women with
      breast cancer undergoing immediate breast reconstruction (IBR) with a TRAM-flap.
      The study was prospective and descriptive and source and method triangulation was
      used. Source triangulation consisted of the patients' and nurses' perspectives,
      whilst method triangulation combined interviews, questionnaires and medical
      records. One result is that the meaning of IBR for the women operated is related
      to feelings of hope, normality and 'wholeness'. Another result is that not all
      the needs of the patients are assessed and met; the nursing care during admission
      is mainly focused on the physical care and after dismissal the patients are left
      in a situation characterized by vulnerability and a sense of emptiness. The study
      points to some implications in the means of quality development and
      rehabilitation.

PMID- 16098116
TI  - A double-blind, crossover study of Biotene Oralbalance and BioXtra systems as
      salivary substitutes in patients with post-radiotherapy xerostomia.
AB  - This study assessed the efficacy of the Bioxtra (BX) and Biotene Oralbalance (OB)
      systems in the treatment of post-radiotherapy xerostomia. In a double-blind,
      crossover study, 20 patients with post-radiotherapy xerostomia were randomly
      allocated to receive either OB then BX, or vice versa, each product for 2 weeks,
      with a 1 week wash-out period in between. Subject-based dry mouth scores derived
      from 100-mm visual analogue scales were recorded at days 0 and 14 of each 2-week
      period, together with subjective perception of changes in dry mouth symptoms.
      Both treatments were effective, resulting in reduction of visual analogue scale
      scores from day 0-14. Between-groups comparisons identified that BX achieved
      significantly better improvements compared with OB for the perception of dry
      mouth and improvements in speech and was also rated as more pleasant to use than
      OB (P < 0.05). In conclusion, both treatments were effective in alleviating the
      symptoms of post-radiotherapy xerostomia, although BX achieved superiority in
      some of the outcomes assessed compared with OB.

PMID- 16098117
TI  - Treatment decision-making in a group of patients with colo-rectal cancer before
      surgery and a one-year follow-up.
AB  - Encouraging patient participation in medical and nursing care is an active
      expression of respect for a person's autonomous choice. The aim of the present
      study was to compare preferences about the degree of participation in treatment
      decision-making in a group of patients with colo-rectal cancer before and one
      year after surgery, and further to compare these preferences to the patients'
      actual participating role before surgery and their sense of coherence. Fifty-five
      persons diagnosed as having rectal or colon cancer were studied. The following
      instruments were used: The Control Preferences Scale (CPS) and the Sense of
      Coherence Scale (SOC). Results show that 71% and 75%, respectively, chose a
      collaborative participation role, before surgery and at follow-up. A majority,
      64%, maintained their preferred role from before surgery to the one-year follow
      up. Agreement between the preferred and the actual participating role was
      achieved by 31%. There were no statistically significant differences between the
      preferred role and with respect to the participants' sense of coherence either
      before surgery or at follow-up. The sense of coherence seemed not to be related
      to the preferences before surgery or at follow-up preferences. Further research
      is needed to elaborate the understanding about patients' preferences for
      participating in treatment and care decisions.

PMID- 16098118
TI  - Acute interstitial pneumonitis during chemotherapy for haematological malignancy.
AB  - Fourteen adult patients with haematological malignancies (eight non-Hodgkin's
      lymphoma, one multiple myeloma, one chronic lymphocytic leukaemia, two acute
      lymphoblastic leukaemia and two acute myeloid leukaemia) developed acute
      interstitial pneumonitis (IP) during the course of chemotherapy. All patients
      manifested high fever over 38 degrees C, bilateral diffuse pulmonary interstitial
      infiltrates in the chest radiograph and severe hypoxia without hypercapnia in the
      arterial blood gas analysis. Pathogenic microorganisms were not detected in
      repeated examinations in any patient. Chemotherapy given included various anti
      neoplastic drugs. Five patients had received granulocyte colony-stimulating
      factor (G-CSF) for chemotherapy-induced leucopenia. The onset was associated with
      an increase of leucocytes in 10 patients. All patients were treated with high
      dose steroid hormone and broad spectrum antibiotics with or without anti-fungal
      agents, and three required mechanical ventilation. Eleven patients quickly
      recovered from these situations, whereas three died. Autopsies were done in two
      patients and disclosed pneumocystis carinii (PC) pneumonitis in one and non
      specific pulmonary congestive oedema and fibrosis in the other. In conclusion, IP
      of unknown cause could develop in patients with various haematological
      malignancies especially at the recovery phase of chemotherapy-induced leucopenia
      irrespective of the previous G-CSF administration. High dose steroid hormone
      should be used as therapy for such patients as soon as possible after exclusion
      of an infective aetiology.

PMID- 16098119
TI  - Referrals to a voluntary sector cancer day care centre: a descriptive study.
AB  - In the UK, recent guidance on supportive and palliative care has acknowledged the
      contribution of voluntary organizations, including their role in palliative day
      care. Similarly, research has tended to focus exclusively on palliative day care
      as opposed to comparable care for people with cancer, regardless of prognosis.
      This paper describes a case record review study conducted at a nurse-led
      voluntary sector cancer day care centre. The study focused on referrals over a
      one-year period in terms of user demographics, referral sources/reasons and
      subsequent care given. It was found that 220 referrals (including 106 self
      referrals) were made during the year. Of these, 70.9% were people with cancer and
      the remainder were carers/bereaved people. Those referred broadly reflected
      national statistics on age, gender and cancer diagnosis. Carers were rarely
      referred by professionals, few lived in inner-city neighbourhoods and some had no
      informal support. Non-specific referral reasons, such as 'support', tended to be
      translated into specific therapies, such as complementary therapies and
      counselling, at initial assessment. Care offered at the centre appeared to
      supplement and complement that provided by local statutory services. The study
      raised issues for practice and further research that may be relevant to those
      working in similar centres.

PMID- 16098120
TI  - The effect of a whole body exercise programme and dragon boat training on arm
      volume and arm circumference in women treated for breast cancer.
AB  - The purpose of this study was to examine the effect of a whole body exercise
      programme and dragon boat training on changes in arm volume in breast cancer
      survivors. A total of 16 female breast cancer survivors with no clinical history
      of lymphoedema volunteered. The 20-week exercise programme consisted of
      resistance and aerobic exercise with the addition of dragon boat training at week
      8. Arm circumference at two sites (CIRC10, CIRC15), arm volume (VOL), and upper
      body strength (1-RM) were measured at baseline (T1), week 8 (T2), and week 20
      (T3). All statistical tests were two-sided (alpha < or = 0.05). No significant
      differences between the ipsilateral and contralateral upper extremities at any of
      the three time points were found. All variables significantly increased from T1
      to T3 (CIRC10: difference, d = 0.49 cm, 95% confidence interval, CI = 0.25-0.73,
      P = 0.000; CIRC15: d = 1.33 cm, CI = 0.78-1.88, P = 0.000; VOL: d = 100 mL, CI =
      69-130, P = 0.000). As well, 1-RM significantly increased from T1 to T3 (d = 10.8
      kg, CI = 5.6-16.1; P = 0.000). In summary, participation in a whole body exercise
      programme and dragon boat training resulted in a significant increase in upper
      extremity volume over time. However, the changes were consistent for both arms
      and the significant gain in upper body muscular strength likely accounted for the
      increase in arm volume.

PMID- 16098121
TI  - Barriers to effective communication across the primary/secondary interface:
      examples from the ovarian cancer patient journey (a qualitative study).
AB  - Effective communication across the primary/secondary interface is vital for the
      planning and delivery of appropriate patient care throughout the cancer patient
      journey. This study describes GPs' views of the communication issues across the
      primary/secondary interface in relation to ovarian cancer patients using
      qualitative interviews with purposively sampled general practitioners (GPs) and
      an audit of hospital medical records of 30 deceased ovarian cancer patients.
      Issues raised by the GPs related to the content and format of communications, but
      of most concern was the tardiness. The time lag between dictation and typing
      letters ranged from 0 to 27 days, with a delay of up to 8 days for signing before
      transit through various mail systems to the GP. Three stages in the patient
      journey were characterized by particular issues: (1) in the pre-diagnostic and
      diagnostic stage was a need for prompt information regarding the results of tests
      and diagnoses, and clearer guidance on the use of tests and fast-track referrals;
      (2) in the active treatment phase, when GPs could lose touch with their patients,
      they needed effective communication in order to provide moral support and crisis
      management; and (3) when oncology withdrew and the focus of care switched back to
      the community for the terminal phase, GPs needed information to enable them to
      pick up the baton of care. There is a need to develop and evaluate interventions
      aimed at improving the content and speed of communications between secondary and
      primary care. Such interventions are likely to be complex and might include the
      greater use of telephone or fax for more selected communications, a review of
      secretarial support, the use of email, the development of GP designed proformas,
      the feasibility of patient/carer letter delivery options, nurse-led
      communication, universal electronic patient records, or a revisiting of the
      patient-held record.

PMID- 16098122
TI  - Scapulo-humeral Paget's sarcoma: Scottish Bone Tumour Registry experience.
AB  - This study aimed to analyse the clinical, radiological and histological features
      of 16 scapulo-humeral Paget's sarcoma cases accrued from Scottish Bone Tumour
      Registry between January 1950 and December 2000. The mean age was 61.5 (range, 44
      77) years with 12 men and 4 women. There were three scapular cases and 13 humeral
      (1 whole length, 5 upper humeral, 5 lower humeral and 2 mid-humeral). These
      patients presented with progressively increasing pain in the shoulder, arm or
      elbow (n = 5), a painful mass associated with a pathological fracture (n = 4), a
      pathological fracture with progressively worsening pain (n = 3), a painful mass
      (n = 3) and a painless mass associated with wrist drop (n = 1). Histology showed
      predominantly osteosarcoma (n = 12), followed by pleomorphic sarcoma (n = 2),
      malignant fibrous histiocytoma (n = 1) and fibrosarcoma (n = 1). Overall, the
      median survival period was 4.5 months. In summary, Paget's sarcoma of the scapulo
      humeral area presents with progressively worsening pain, a painful mass with or
      without a pathological fracture, predominantly lytic in humeral and purely
      sclerotic in scapular lesions, osteosarcoma-dominant histology, primarily treated
      with an early limb ablative surgery and associated with a poor 1-year survival
      (12.5%) and 5-year survival (6.2%) rate.

PMID- 16098123
TI  - Caring and curing: paediatric cancer services since 1960.
AB  - This paper traces the history of the specialist meanings of 'cure' in paediatric
      oncology in the UK, how they have changed with increasing organization of the
      discipline, ever-rising survival rates for all childhood cancers, and with
      feedback from patients and families. It examines the differing ways in which
      those involved in researching, treating, and raising funds for work on childhood
      cancers have understood and used the language of cure, and speculates as to why
      talking about the 'cure' of survivors of childhood cancers is so problematic. The
      paper discusses the particular importance of holistic care in the development of
      paediatric oncology. Psychosocial support is delivered alongside surgery,
      radiotherapy and chemotherapy. The focus for support is the patient's whole
      family, building a tenet of palliative care into curative treatment. The concept
      of the 'truly cured child' is argued to have been crucial in the discipline's
      decision in the 1970s and 1980s to make the psychosocial needs of patients and
      their families central in the programme of curing children with cancer.

PMID- 16098125
TI  - Experimental approaches to lymphocyte migration in dermatology in vitro and in
      vivo.
AB  - Lymphocyte trafficking through the dermal compartment is part of the
      physiological surveillance process of the adaptive immune system. On the other
      hand, persistent or recurrent lymphocyte infiltrates are hallmarks of both types
      of chronic inflammatory skin diseases, Th1-type such as psoriasis or Th2/allergic
      type like atopic dermatitis. A better understanding of the mechanisms underlying
      lymphocyte movements is one of the key prerequisites for developing more
      effective therapies. In this review, we introduce a range of simple-to
      sophisticated experimental in vitro and in vivo approaches to analyze lymphocyte
      migration. These methods start from static in vitro adhesion and chemotaxis
      assays, include dynamic endothelial flow chamber, intravital dual photon, and
      transcutaneous live-video microscopy, and finally encompass specific genetically
      deficient or engineered animal models. Discussing pros and cons of these assay
      systems hopefully generates both state-of-the-art knowledge about the factors
      involved in most common chronic skin diseases as well as an improved
      understanding of the limitations and chances of new biologic pharmaceuticals that
      are currently introduced into clinical practice.

PMID- 16098126
TI  - Identification of differentially expressed genes in psoriasis using expression
      profiling approaches.
AB  - To identify differentially expressed genes which play causal roles in
      pathogenesis and maintenance for psoriasis, we used BodyMapping and introduced
      amplified fragment length polymorphism approaches. From the BodyMap database, we
      selected 2007 genes which specifically expressed in epithelial tissues. Among
      2007 genes, we surveyed genes which differentially expressed in involved or
      uninvolved psoriatic lesional skin samples compared with atopic dermatitis,
      mycosis fungoides, and normal skin samples. As a result of surveying 2007 genes,
      241 genes were differentially expressed only in involved psoriatic skin but not
      in the other samples. Hierarchical cluster analysis of gene expression profiles
      showed that 13 independent psoriatic-involved skin samples clustered tightly
      together, reflecting highly similar expression profiles. Using the same 2007 gene
      set, we examined gene expression levels in five serial lesions from distal
      uninvolved psoriatic skin to involved psoriatic plaque. We identified seven genes
      such as alpha-1-microglobulin/bikunin precursor, calnexin, claudin 1, leucine
      zipper down-regulated in cancer 1, tyrosinase-related protein 1, Yes-associated
      protein 1, and unc-13-like protein (Coleonyx elegans) which show high-expression
      levels only in uninvolved psoriatic lesions. These seven genes, which were
      reported to be related to apoptosis or antiproliferation, might have causal roles
      in pathophysiology in psoriasis.

PMID- 16098127
TI  - A novel tetracationic phthalocyanine as a potential skin phototherapeutic agent.
AB  - An amphiphilic tetracationic derivative of Zn(II)-phthalocyanine (RLP068) was
      prepared by means of chemical synthesis and was showed to possess efficient
      photophysical and photosensitizing properties against model biological
      substrates. RLP068 was incorporated into a gel formulation, which allowed its
      ready penetration into the epidermal layers, but not into the dermis, of both
      Balb/c and hairless SKH1 mice after 1-2 h of topical deposition. Pharmacokinetic
      studies showed that the phthalocyanine thus formulated does not enter the general
      blood circulation. The epidermis-associated amount of phthalocyanine was
      sufficient to cause an important cutaneous damage upon irradiation with red light
      (600-700 nm; 100-180 mW/cm(2), 160 J/cm(2)); the latter was confined to the
      epidermal area with no apparent diffusion to the underlying dermal layers or
      appearance of photosensitivity in distal skin areas. A systematic investigation
      of the interplay among the different parameters (deposition time of the
      formulated phthalocyanine on mouse skin, irradiation fluence rate and total light
      fluence) allowed us to identify the minimal phototoxic dose, as well as to define
      irradiation protocols allowing the repeatability of the phototherapeutic
      treatment. The potential of RLP068 to act as a PDT agent for cutaneous diseases
      is briefly discussed.

PMID- 16098128
TI  - Changes in basal cell mitosis and transepidermal water loss in skin cultures
      treated with vitamins C and E.
AB  - Three variants of the living skin equivalent cultures were compared in order to
      determine the most suitable to grow human differentiated epidermis to test
      beneficial properties of nutrients. Criteria of culture quality were mitotic
      index and transepidermal water loss (TEWL) assayed by means of a ServoMed
      Evaporimeter EP-2TM (ServoMed, Kinna, Sweden). Standards were donor skin mean
      mitotic index 11.1% and TEWL of living subjects mean 6.4 g/m(2)/h. Cultures (i)
      in 5% serum, 10 ng/ml of epidermal growth factor (EGF) at 37 degrees C and 95%
      relative humidity (RH); mitotic index on day 14, 19.2%, but on day 21, 1.8% and
      TEWL 9.5 g/m(2)/h on day 18. (ii) In 1% serum, no EGF, 33 degrees C and 95% RH,
      mitotic index on day 21, 9.1% and TEWL, 9.5% on day 18. (iii) Culture in same
      medium, 33 degrees C and 60% RH, mitotic index on day 28, 9.5% and TEWL 6.1
      g/m(2)/h on day 18 as in vivo. Incubation in 60% RH was achieved using a novel
      chamber and dishes exposing only the corneum, sealing the medium. Vitamins C and
      E were used as model test nutrients. Culture conditions were 1% serum, no EGF at
      33 degrees C and 95% RH. Vitamin C at 142 and 284 microM increased the mitotic
      index after 10- and 15-day treatment, but at 586 microM it was weakly toxic.
      Vitamin E at 20 and 40 microM did not. Both vitamins reduced TEWL providing
      functional data in support of previous reports on barrier properties. These are
      functional biomarkers of skin benefit relevant to skin in vivo.

PMID- 16098129
TI  - Structural optimization of pep7, a small peptide extracted from epimorphin, for
      effective induction of hair follicle anagen.
AB  - Epimorphin is representative of a unique class of stromal membrane-anchored
      proteins that plays distinct functions depending on its membrane topology. When
      exposed extracellularly, this molecule acts as a morphoregulator for various
      tissues including hair follicle epithelia. Previous study identified its
      functional domain (the pep7 domain: SIEQSCDQDE) for hair follicular morphogenesis
      followed by the successful generation of a chemically modified active peptide.
      Here, we report optimization of this peptide by the introduction of sequential
      mutations and subsequent structural determination. We found that three residues
      from the C-terminus are dispensable, and alternation of the seventh amino acid to
      an Alanine residue enhanced activity. To favour the biologically active
      conformation, epsilon-Acp (NH(CH(2))(5)CO) linked to a Cysteine residue was
      connected at the N-terminus followed by the introduction of an intramolecular
      disulphide bridge, the modification process of which could be included in the
      peptide synthesis. The obtained modified peptide, termed 'EPM (epimorphin
      derived) peptide', has a Mw of 950 Da and exerts an inductive effect on hair
      follicle regeneration at a concentration of approximately 0.00001% or even lower.
      The action of this EPM peptide was more apparent in mice treated with 1%
      minoxidil, suggesting its potential clinical benefit as a new type of hair
      regenerating agent.

PMID- 16098130
TI  - CD44, but not l-selectin, is critically involved in leucocyte migration into the
      skin in a murine model of allergic dermatitis.
AB  - CD44 and l-selectin (CD62L) are major adhesion receptors that mediate leucocyte
      recruitment at inflammatory sites and lymph nodes, by supporting cell rolling
      under blood flow. Both CD44 and CD62L have been implicated in inflammatory skin
      disorders, but their specific involvement in an immediate-type allergic reaction
      remains uncertain. We used mice deficient in CD44 or CED62L or both in order to
      determine whether one or both of these molecules were required for leucocyte
      extravasation in an atopic dermatitis-like allergic response. Wild-type (WT) mice
      and mice deficient in CD44, CD62L or both were immunized with ovalbumin (OVA).
      Inflammatory reaction in the ear was elicited once by means of intradermal
      injection of OVA. Effective sensitization of CD62L knockout (KO) mice required
      intraperitoneal antigen injection; however, OVA-specific T helper 2 (Th2)-type
      immune responses and IgE production in mice lacking CD44, CD62L or both were
      comparable to those in WT mice following intraperitoneal immunization. We
      employed intravital videomicroscopy to monitor the recruitment of fluorescence
      labelled leucocytes to the ear tissue following challenge with OVA. The number of
      adherent leucocytes was significantly reduced in CD44 KO and CD44/CD62L double KO
      mice, indicating that CD44 was involved in firm adhesion, the committed step of
      leucocyte extravasation. Histology of the OVA-challenged ears showed a diminished
      leucocyte infiltration in the ears of CD44 KO and double KO mice. The results of
      our study demonstrate that CD44, but not CD62L, is required for leucocyte
      extravasation during a Th2-type inflammatory response.

PMID- 16098131
TI  - MEL4B3, a novel mRNA is induced in skin tumors and regulated by TGF-beta and pro
      inflammatory cytokines.
AB  - Tumor-stroma interactions play a decisive role in the growth and metastasis of
      solid tumors, and involve signalling either by soluble mediators or direct cell
      cell interaction. Here, we report the isolation and characterisation of a novel
      cDNA (MEL4B3), which is induced in cultured dermal fibroblasts exposed to
      supernatants of melanoma cell lines. MEL4B3 shares high homology with two
      predicted cDNA sequences for which no activity has so far been described. In situ
      hybridisation revealed the expression of MEL4B3 in malignant melanoma increasing
      with tumor depth; in basal cell carcinoma and in squamous cell carcinoma. MEL4B3
      was barely detectable in normal skin or non-malignant melanocytic naevi.
      Furthermore, MEL4B3 was expressed at high level in the epidermis of psoriatic
      skin. In vitro, the expression of MEL4B3 was found to be induced by the exposure
      of human dermal fibroblasts to melanoma cell culture supernatants or to
      transforming growth factor-beta, interleukin-1 and tumor necrosis factor-alpha.
      The expression MEL4B3 therefore reflects closely cell activation occurring during
      tumor growth, metastasis and inflammation.

PMID- 16098132
TI  - Understanding Fragile X syndrome: molecular, cellular and genomic neuroscience at
      the crossroads.

PMID- 16098133
TI  - FMRP RNA targets: identification and validation.
AB  - The Fragile X Syndrome is caused by the loss of function of the FMR1 gene
      (Pieretti et al. 1991. Cell 66, 817-822; O'Donnell & Warren 2002. Annu Rev
      Neurosci 25, 315-338]. Identification of the RNA targets to which FMRP binds is a
      key step in understanding the function of the protein and the cellular defects
      caused by its absence (Darnell et al. 2004 Ment Retard Dev Disabil Res Rev 10, 49
      52). Here we discuss the current understanding of FMRP as an RNA-binding protein,
      the different approaches that have been taken to identify FMRP RNA targets and
      the relevance of some of these approaches to FMRP biology. In addition, we
      present evidence that point mutations in the K-homology (KH)1 or KH2 domains of
      FMRP abrogate its polyribosome association in transfected neuroblastoma cells but
      that the deletion of the RGG box does not. This suggests that RNA binding by the
      RGG box of FMRP may mediate other aspects of cellular mRNA metabolism such as
      mRNA localization or that it may have a role downstream of polyribosome
      association.

PMID- 16098134
TI  - Localization of FMRP-associated mRNA granules and requirement of microtubules for
      activity-dependent trafficking in hippocampal neurons.
AB  - Fragile X syndrome is caused by the absence of the fragile X mental-retardation
      protein (FMRP), an mRNA-binding protein, which may play important roles in the
      regulation of dendritic mRNA localization and/or synaptic protein synthesis. We
      have recently applied high-resolution fluorescence imaging methods to document
      the presence, motility and activity-dependent regulation of FMRP granule
      trafficking in dendrites and spines of cultured hippocampal neurons. In this
      study, we show that FMRP granules distribute to F-actin-rich compartments,
      including filopodia, spines and growth cones during the staged development of
      hippocampal neurons in culture. Fragile X mental-retardation protein granules
      were shown to colocalize with ribosomes, ribosomal RNA and MAP1B mRNA, a known
      FMRP target, which encodes a protein important for microtubule and actin
      stabilization. The levels of FMRP within dendrites were reduced by disruption of
      microtubule dynamics, but not by disruption of F-actin. Direct measurements of
      FMRP transport kinetics using fluorescence recovery after photobleaching in
      living neurons showed that microtubules were required to induce the mGluR
      dependent translocation into dendrites. This study provides further
      characterization of the composition and regulated trafficking of FMRP granules in
      dendrites of hippocampal neurons.

PMID- 16098135
TI  - Differential translation and fragile X syndrome.
AB  - Fragile X syndrome (FXS) is caused by the transcriptional silencing of the Fmr1
      gene, which encodes a protein (FMRP) that can act as a translational suppressor
      in dendrites, and is characterized by a preponderance of abnormally long, thin
      and tortuous dendritic spines. According to a current theory of FXS, the loss of
      FMRP expression leads to an exaggeration of translation responses linked to group
      I metabotropic glutamate receptors. Such responses are involved in the
      consolidation of a form of long-term depression that is enhanced in Fmr1 knockout
      mice and in the elongation of dendritic spines, resembling synaptic phenotypes
      over-represented in fragile X brain. These observations place fragile X research
      at the heart of a long-standing issue in neuroscience. The consolidation of
      memory, and several distinct forms of synaptic plasticity considered to be
      substrates of memory, requires mRNA translation and is associated with changes in
      spine morphology. A recent convergence of research on FXS and on the involvement
      of translation in various forms of synaptic plasticity has been very informative
      on this issue and on mechanisms underlying FXS. Evidence suggests a general
      relationship in which the receptors that induce distinct forms of efficacy change
      differentially regulate translation to produce unique spine shapes involved in
      their consolidation. We discuss several potential mechanisms for differential
      translation and the notion that FXS represents an exaggeration of one 'channel'
      in a set of translation-dependent consolidation responses.

PMID- 16098136
TI  - Come FLY with us: toward understanding fragile X syndrome.
AB  - The past few years have seen an increased number of articles using Drosophila as
      a model system to study fragile X syndrome. Phenotypic analyses have demonstrated
      an array of neuronal and behavioral defects similar to the phenotypes reported in
      mouse models as well as human patients. The availability of both cellular and
      molecular tools along with the power of genetics makes the tiny fruit fly a
      premiere model in elucidating the molecular basis of fragile X syndrome. Here, we
      summarize the advances made in recent years in the characterization of fragile X
      Drosophila models and the identification of new molecular partners in neural
      development.

PMID- 16098137
TI  - Therapeutic implications of the mGluR theory of fragile X mental retardation.
AB  - Evidence is reviewed that the consequences of group 1 metabotropic glutamate
      receptor (Gp1 mGluR) activation are exaggerated in the absence of the fragile X
      mental retardation protein, likely reflecting altered dendritic protein
      synthesis. Abnormal mGluR signaling could be responsible for remarkably diverse
      psychiatric and neurological symptoms in fragile X syndrome, including delayed
      cognitive development, seizures, anxiety, movement disorders and obesity.

PMID- 16098139
TI  - Regulated expression and dynamic changes in subnuclear localization of mammalian
      Rad18 under normal and genotoxic conditions.
AB  - Rad18 plays a crucial role in postreplication repair in both lower eukaryotes and
      higher eukaryotes. However, regulation of the Rad18 expression in higher
      eukaryotes is largely unknown. We found that the RAD18 transcript is expressed
      ubiquitously in various tissues and very highly in the testis in mammals.
      Although human RAD18 (hRAD18) transcription levels fluctuate during the cell
      cycle, being maximal in the late S and minimal in the early G1, the protein
      levels remain constant throughout the cell cycle. Following UV-irradiation,
      hRAD18 transcription levels decrease significantly, but Rad18 protein levels
      change little. The protein levels are maintained at least in part by enhanced
      translation rates. hRad18 localizes in the nucleus in two forms: a diffused form
      and a condensed form forming nuclear dots. These nuclear dots disperse rapidly in
      the nucleoplasm after treatments with various genotoxic agents, resulting in an
      enhancement of the intranuclear Rad18 concentration of the diffused form. No de
      novo protein synthesis is required for this process. These results suggest that
      in higher eukaryotes, the maintenance and dynamic translocation of Rad18 protein
      is important for postreplication repair.

PMID- 16098140
TI  - DNA methylation of Sleeping Beauty with transposition into the mouse genome.
AB  - The Sleeping Beauty transposon is a recently developed non-viral vector that can
      mediate insertion of transgenes into the mammalian genome. Foreign DNA elements
      that are introduced tend to invoke a host-defense mechanism resulting in
      epigenetic changes, such as DNA methylation, which may induce transcriptional
      inactivation of mammalian genes. To assess potential epigenetic modifications
      associated with Sleeping Beauty transposition, we investigated the DNA
      methylation pattern of transgenes inserted into the mouse genome as well as
      genomic regions flanking the insertion sites with bisulfite-mediated genomic
      sequencing. Transgenic mouse lines were created with two different Sleeping
      Beauty transposons carrying either the Agouti or eGFP transgene. Our results
      showed that DNA methylation in the keratin-14 promoter and Agouti transgene were
      negligible. In addition, two different genomic loci flanking the Agouti insertion
      site exhibited patterns of DNA methylation similar to wild-type mice. In
      contrast, high levels of DNA methylation were observed in the eGFP transgene and
      its ROSA26 promoter. These results indicate that transposition via Sleeping
      Beauty into the mouse genome may result in a significant level of de novo DNA
      methylation. This may depend on a number of different factors including the cargo
      DNA sequence, chromosomal context of the insertion site, and/or host genetic
      background.

PMID- 16098141
TI  - Wnt signaling regulates the sequential onset of neurogenesis and gliogenesis via
      induction of BMPs.
AB  - In the mammalian central nervous system, neurogenesis precedes gliogenesis;
      neurons are primarily generated at the neural stage, whereas most glial cells are
      generated perinatally and postnatally. However, the signals that regulate this
      sequence of events remain unclear. Here we show that Wnt signaling induces
      neuronal and astroglial differentiation but suppresses oligodendroglial
      differentiation. We observed that precursor cells infected with a retrovirus
      encoding beta-catenin differentiated into neurons, while astrocytes developed
      from uninfected precursor cells surrounding infected cells. As neurogenesis
      proceeded, expression of the bone morphogenetic proteins (BMPs), BMP2, 4 and 7,
      progressively increased in the cells infected with the retrovirus encoding beta
      catenin. Furthermore, treatment of cells with Noggin, a BMP antagonist,
      completely inhibited astroglial differentiation but partially restored
      oligodendroglial differentiation. These results suggest that Wnt signaling
      indirectly regulates gliogenesis by inducing BMPs in neuronal cells. Thus,
      cooperation between Wnt and BMP signaling may play a key role in determining the
      sequence of neurogenesis and gliogenesis.

PMID- 16098142
TI  - Identification and characterization of a novel member of murine semaphorin
      family.
AB  - The semaphorin gene family contains a large number of secreted type or
      transmembrane type proteins, and some of them function as the repulsive and
      attractive cues of axon guidance during development. Here we report a novel
      member of murine class 3 semaphorin genes, semaphorin 3G (Sema3G), mapped on
      chromosome 14. In adulthood, Sema3G is mainly expressed in the lung and kidney,
      and a little in the brain. Interestingly, in the adult rodent brain Sema3G is
      expressed only in the granular layer of the cerebellum, as determined by Northern
      blot and in situ hybridization analyses. We also found that Sema3G binds
      Neuropilin-2, but not Neuropilin-1, and induces the repulsion of sympathetic
      axons, but not dorsal root ganglion axons, indicating that Sema3G utilizes
      Neuropilin-2 as a receptor to repel specific types of axons.

PMID- 16098143
TI  - Inhibition of cholesterol biosynthesis by 25-hydroxycholesterol is independent of
      OSBP.
AB  - 25-hydroxycholesterol (25-HC) is a potent suppressor of cholesterol synthesis
      gene transcription in cultured cells. A high affinity binding protein for 25-HC,
      oxysterol-binding protein (OSBP), has been identified from tissue cytosol. OSBP
      translocates from the cytosol to the Golgi apparatus membranes after addition of
      25-HC to cell cultures and is thought to mediate 25-HC action on cholesterol
      metabolism through association to the Golgi apparatus. However, direct evidence
      to prove this hypothesis was lacking. In this study, we knocked down expression
      of OSBP by using duplex siRNAs specific for OSBP to examine the relationship
      between OSBP and 25-HC-induced inhibition of cholesterol synthesis gene
      transcription. We found that decreasing OSBP expression by approximately 90% did
      not affect 25-HC-induced inhibition of transcription of 3-hydoxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase and squalene epoxidase to any extent. Exogenous
      lysophosphatidylcholine (LPC), which is known to cause the efflux of cellular
      cholesterol into the medium and to increase cholesterol synthesis, was found to
      rescue the 25-HC-induced down-regulation of sterol regulated genes, while LPC did
      not affect 25-HC-induced association of OSBP with the Golgi apparatus. These
      results suggest that inhibition of cholesterol biosynthesis genes by 25-HC is
      OSBP-independent.

PMID- 16098144
TI  - Inhibition of the 53BP2S-mediated apoptosis by nuclear factor kappaB and Bcl-2
      family proteins.
AB  - The p53 binding protein 2 (53BP2) has been identified independently as the
      interacting protein to p53, Bcl-2, and p65 subunit of nuclear factor kappaB (NF
      kappaB). It was demonstrated that over-expression of 53BP2 (renamed as 53BP2S)
      induces apoptotic cell death. In this study we explored the effect of NF-kappaB
      activation elicited by a physiological NF-kappaB inducer, interleukin-1beta (IL
      1beta), and anti-apoptotic Bcl-2 family proteins on the 53BP2S-mediated
      apoptosis. We found that both NF-kappaB activation and Bcl-2 family proteins
      could prevent the 53BP2S-mediated depression of mitochondrial transmembrane
      potential, activation of caspase-9, cleavage of poly ADP ribose polymerase
      (PARP), and cell death. These observations suggested that 53BP2S/Bbp and its
      directly or indirectly interacting proteins might play crucial roles in the
      regulation of apoptosis and contribute to carcinogenesis. It is also suggested
      that 53BP2S/Bbp induces apoptosis through the mitochondrial death pathway
      presumably by counteracting the actions of anti-apoptotic Bcl-2 family proteins.
      The regulatory network of the 53BP2S-mediated apoptosis cascade including its
      interacting proteins is discussed.

PMID- 16098145
TI  - Drosophila melanogaster Rac2 is necessary for a proper cellular immune response.
AB  - It has been reported that during Drosophila embryonic development, and in cell
      culture, that the Rac GTPases are redundant. To better elucidate Rac function in
      Drosophila, we decided to study the role of Rac2 in larval cellular defense
      reactions against the parasitiod Leptopilina boulardi. Here we show a dramatic
      effect in the context of cellular immunity where, unlike embryonic development,
      Rac2 appears to have a non-redundant function. When an invading parasitoid is
      recognized as foreign, circulating hemocytes (blood cells) should recognize and
      attach to the egg chorion. After attachment the hemocytes should then spread to
      form a multilayered capsule surrounding the invader. In Rac2 mutants this process
      is disrupted. Immune surveillance cells, known as plasmatocytes, adhere to the
      parasitoid egg but fail to spread, and septate junctions do not assemble,
      possibly due to mislocalization of the Protein 4.1 homolog Coracle. Finally,
      larger cells known as lamellocytes attach to the capsule but also fail to spread,
      and there is a lack of melanization. From these results it appears that Rac2 is
      necessary for the larval cellular immune response.

PMID- 16098146
TI  - ROCK-I and ROCK-II cooperatively regulate closure of eyelid and ventral body wall
      in mouse embryo.
AB  - Rho-associated kinase (ROCK) is a serine/threonine kinase working in the Rho
      signaling to actin cytoskeleton. We previously reported that loss of ROCK-I
      results in the eyelid open at birth (EOB) and omphalocele phenotype in mice,
      while loss of ROCK-II results in placental dysfunction leading to intrauterine
      growth retardation and fetal death. Here, we report that after backcross to the
      C57BL/6 N genetic background, ROCK-II knockout (KO) neonates are born also with
      open eyelid and umbilical hernia, a phenotype similar to that of ROCK-I KO mice.
      ROCK-II KO embryos show impaired extension of the eyelid epithelial sheet with
      disorganized actin bundles in the leading edge of the sheet. These results
      suggest that ROCK-I and ROCK-II cooperatively regulates the assembly of actin
      bundles essential for closure of the eyelid and ventral body wall in mouse
      embryos. Consistently, ROCK-I(+/-)ROCK-II(+/-) double heterozygous mice also show
      the EOB and omphalocele phenotype.

PMID- 16098147
TI  - Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by
      SUMO modification.
AB  - Megakaryoblastic leukemia 1 (MKL1) was originally identified as a gene
      translocated in megakaryoblastic leukemia. It has been shown that MKL1 functions
      as a RhoA-regulated transcriptional coactivator of serum response factor (SRF).
      In order to identify a protein that regulates the function of MKL1, we performed
      yeast two-hybrid screening and isolated cDNA that encodes UBC9, an E2 enzyme of
      small ubiquitin-related modifier-1 (SUMO-1), as an MKL1-binding protein. UBC9 was
      found to physically interact with MKL1 by GST pull-down assay, and MKL1 was
      covalently modified with SUMO-1 in 293T cells and in vitro reconstitution system.
      MKL1 sumoylation is enhanced by either serum stimulation or co-expression of
      constitutively active form of RhoA. Mutational analysis showed that lysine
      residues at 499, 576, and 624 are the major acceptor sites for SUMO-1. In
      addition, reporter gene analysis revealed that mutation of the three sumoylation
      sites strongly enhances the transcriptional activity of MKL1. The covalent
      attachment of SUMO-1 to MKL1 by gene fusion represses MKL1-dependent
      transcription in a complementary manner. Finally, mutation of the sumoylation
      sites of MKL1 also enhances SRF-dependent transcription without affecting MKL1
      SRF interaction. The combined results demonstrated that MKL1 is sumoylated and
      this modification represses transcriptional activity of MKL1.

PMID- 16098148
TI  - SEI family of nuclear factors regulates p53-dependent transcriptional activation.
AB  - SEI family proteins, p34SEI-1 and SEI-2(TRIP-Br2), are nuclear factors that are
      implicated in cell cycle regulation through interaction with CDK4/CyclinD and E2F
      1/DP-1 complexes. Here we report that the SEI family proteins regulate
      transcriptional activity of p53 tumor suppressor protein. Expression of SEI-1,
      SEI-2 or SEI-3 strongly stimulates p53-dependent gene activation in HeLa and U2OS
      cells but not in p53-deficient Saos2 or p53-knockdown HeLa cells. SEI proteins
      possess an intrinsic transactivation activity, interact with the coactivator CREB
      binding protein, and cooperate synergistically with the ING family of chromatin
      associated proteins to stimulate the transactivation function of p53. Doxycycline
      induced expression of SEI proteins results in activation of the p21 gene and
      inhibition of cell growth, but the growth arrest was not suppressed by the siRNA
      mediated knockdown of the endogenous p53 protein. These results indicate that the
      SEI family of nuclear proteins regulates p53 transcriptional activity and a p53
      independent signaling pathway leading to growth inhibition.

PMID- 16098149
TI  - Understanding health information, communication, and information seeking of
      patients and consumers: a comprehensive and integrated model.

PMID- 16098150
TI  - From rhetoric to reality: including patient voices in supportive cancer care
      planning.
AB  - OBJECTIVE: To explore the extent and manner of patient participation in the
      planning of regional supportive care networks throughout the province of Ontario.
      We consider the disconnect between the rhetoric and reality of patient
      involvement in network planning and co-ordination. CONTEXT: In 1997, the Province
      of Ontario, Canada, established a new, regionalized cancer care system. By
      transferring responsibility to the regional level and to networks, the architects
      of the new provincial system hoped to broaden participation in decision making
      and to enhance the responsiveness of decisions to communities. RESEARCH APPROACH:
      Through a qualitative, multiple case study approach we evaluated the processes of
      involving patients in network development. In-depth, semi-structured interviews
      and document analysis were complemented by observations of provincial meetings,
      regional council and network meetings. RESULTS: The network development processes
      in the three case study regions reveal a significant gap between intentions to
      involve patients in health planning and their actual involvement. This gap can be
      explained by: (i) a lack of clear direction regarding networks and patient
      participation in these networks; (ii) the dominance of regional cancer centres in
      network planning activities; and, (iii) the emergence of competing provincial
      priorities. DISCUSSION: These three trends expose the complexity of the notion of
      public participation and how it is embedded in social and political contexts. The
      failed attempt at involving patients in health planning efforts is the result of
      benign neglect of public participation intents and the social and political
      contexts in which public and patient participation is meant to occur.

PMID- 16098151
TI  - 'Working the system'. Achieving change through partnership working: an evaluation
      of cancer partnership groups.
AB  - AIMS AND OBJECTIVES: To investigate the characteristics and achievements of
      cancer partnership groups--collaborative service improvement groups formed of NHS
      staff and service users--in the 34 cancer networks in England, and in particular
      to explore the influence that such groups had on local cancer services. DESIGN: A
      qualitative approach employing a structured telephone survey, face-to-face
      interviews and documentary analysis. PARTICIPANTS AND SETTING: Thirty cancer
      networks in England with an active Partnership Group completed the telephone
      survey. From these 30 networks, six networks were subsequently selected from
      which service users and NHS professionals involved in partnership groups and NHS
      professionals who were non-members were recruited to take part in face-to-face
      interviews. RESULTS AND CONCLUSIONS: Partnership groups were established in the
      majority of cancer networks. Typically, these groups were at network level, been
      established for less than a year, met once every 2 months, and were populated
      with both service users and health-care professionals. Five common activities and
      achievements were identified: establishment of the group itself; acting as a
      'reference' group for consultation; networking and representation on other
      groups; patient information and communication and proactive influencing.
      Activities progressed in scale and complexity as groups evolved. Groups had
      learnt the basics of change management and some identified a more sophisticated
      understanding of change processes in the NHS as essential for the group's
      motivation and survival. When gauging the impact of involvement strategies it
      would seem important to subscribe to broad indicators of success that include
      both process and outcome measures.

PMID- 16098152
TI  - Opinions of women with high inherited breast cancer risk about prophylactic
      mastectomy: an initial evaluation from a screening trial including magnetic
      resonance imaging and ductal lavage.
AB  - OBJECTIVE: Prophylactic mastectomy (PM) is often considered, but variably chosen
      by women at high inherited risk of breast cancer; few data exist on patient
      tolerance of intensive breast screening as an alternative to PM. We performed an
      evaluation of high-risk women's tolerance of a breast screening protocol using
      clinical breast examination, mammography, breast magnetic resonance imaging (MRI)
      and ductal lavage (DL), and of change in attitudes toward PM after screening.
      DESIGN: A questionnaire assessing tolerance of screening procedures and change in
      opinion towards PM was designed and administered to 43 study participants, after
      a median follow-up of 13 months. Responses were evaluated according to patient
      characteristics, including type of study-prompted interventions, BRCA mutation
      status, and prior history of cancer, via univariate analysis. RESULTS: Most
      patients [85.3% (68.9-95.1%)] were more opposed or unchanged in their attitudes
      towards PM after study participation, with only 14.7% (5.0-31.1%) less opposed (P
      = 0.017) despite a short-interval follow-up MRI rate of 71.7% and a biopsy rate
      of 37%. Lower rates of maximal discomfort were reported with mammogram [2.8% (0
      14.5%)] and MRI [5.6% (0-18.7%)] than with DL [28.6% (14.6-46.3%)], with P =
      0.035. CONCLUSIONS: Most high-risk women tolerated intensive breast screening
      well; they were not more inclined towards PM after participating. Future studies
      should prospectively evaluate larger numbers of high-risk women via multivariate
      analysis, to determine characteristics associated with preference for breast
      screening vs. PM.

PMID- 16098154
TI  - Patient attitudes to clinical trials: development of a questionnaire and results
      from asthma and cancer patients.
AB  - OBJECTIVE: To develop a questionnaire to assess patients' views of clinical
      trials, and to report the results from the questionnaire in two patient groups:
      asthma and cancer. DESIGN: A 43 item questionnaire asking patients about their
      views to clinical trials was developed on the basis of interviews with trialists
      and focus groups with patients. The questionnaire was mailed to patients with a
      diagnosis of either asthma or cancer. A set of items was then selected, via
      statistical analyses, to form the core of the questionnaire. PARTICIPANTS:
      Patients with a diagnosis of cancer in one NHS Hospital Trust, and patients with
      a diagnosis of asthma in two NHS Hospital Trusts. RESULTS: Completed
      questionnaires were received from 353 cancer patients and 578 asthma patients.
      Factor analyses of the data indicated that 22 items contributed to five
      dimensions: 'positive beliefs', 'safety', 'information needs', 'negative
      expectations' and 'patient involvement'. Differences between asthma and cancer
      patients on these dimensions were small. A regression of these dimension scores
      against a variable asking if patients would be willing to take part in trials
      found that 'safety' and 'information needs' did not contribute significantly to
      the model for either asthma or cancer patients. CONCLUSIONS: A questionnaire has
      been developed for use in assessing patients' views towards clinical trials.
      Results from the surveys reported here suggest that patient views about the
      importance of trials and beliefs about the value of patient involvement are
      likely to be predictive of whether or not patients will agree to take part in a
      study.

PMID- 16098153
TI  - Psychosexual health 5 years after hysterectomy: population-based comparison with
      endometrial ablation for dysfunctional uterine bleeding.
AB  - BACKGROUND: We report a population-based comparison of psychosexual health 5
      years after contrasting amounts of surgical treatments for heavy periods
      [dysfunctional uterine bleeding (DUB)]. Women's fears about sexual function after
      hysterectomy might not be unfounded. The psychosexual problems may return and/or
      develop with time. The removal of ovaries at the time of hysterectomy is
      associated with greater deterioration of self-reported sexual function. Surgical
      menopause significantly impairs sexual wellbeing. We failed to observe uniform
      beneficial effects of hormone replacement therapy (HRT) on reported psychosexual
      health. OBJECTIVE: To compare self-reported bothersome sexual function; loss of
      interest in sex, difficulty in becoming sexually excited and vaginal dryness 5
      years after surgical management of DUB [transcervical endometrial
      resection/ablation (TCRE) or subtotal and total hysterectomy, with and without
      prophylactic bilateral oophorectomy (BO)]. DESIGN: Prospective cohort study up to
      5 years post-surgery for DUB, TCRE or hysterectomy, with or without BO. SETTING:
      Over 400 NHS and private hospitals in England, Northern Ireland and Wales.
      COHORT: Of 11,325 women who responded to the 5-year questionnaire, over 9500
      (84%) were valid cases, and over 8900 (94%) did complete the questions relating
      to psychosexual function. Most were between the ages of 39 and 45 years, married
      or cohabiting. MAIN OUTCOMES: Self-reported experience of bother, recorded as
      'some', 'severe' and 'extreme', to questions on (1) libido loss, (2) difficulty
      with sexual arousal, and (3) vaginal dryness during the past 4 weeks, 5 years
      after surgery. RESULTS: Five years after surgery for DUB, the crude and adjusted
      prevalence of psychosexual problems was higher after hysterectomy than after
      TCRE. Amongst the women with concurrent BO, the age- and HRT-adjusted odds ratios
      for extreme psychosexual problems were increased by 80% (libido loss), 82%
      (difficult sex arousal) and 69% (vaginal dryness) compared with TCRE.
      CONCLUSIONS: Five years after hysterectomy more women reported having bothersome
      psychosexual function than did the women who had a less invasive operation.
      Hormone therapy, although related to surgical method, did not reduce this long
      term detrimental effect. The odds were particularly high amongst women with
      concurrent BO. Women should be advised that they might be at higher risk of
      psychosexual problems following hysterectomy, compared with a less invasive
      procedure.

PMID- 16098155
TI  - Patients' priorities concerning health research: the case of asthma and COPD
      research in the Netherlands.
AB  - BACKGROUND: Although patients are increasingly involved in agenda setting within
      specific fields of health research, they rarely participate in decision-making on
      the entire breadth of health research, including biomedical research. This might
      be attributable to a widely held view that patients are incapable of adequate
      research prioritization due to a lack of relevant knowledge, a failure to look
      beyond their own individual problems or an inability to objectively consider long
      term targets. AIMS: By conducting transparent and structured consultations with
      asthma and chronic obstructive pulmonary disease (COPD) patients regarding their
      health research priorities, we aim to assess the ability of patients to
      prioritize research in a well-argued way. METHODS: Patients were consulted
      through seven focus groups, a feedback meeting, and a questionnaire. The focus
      groups and the feedback meeting aimed to explore the entire breadth of patients'
      problems experienced in relation to their diseases, while the questionnaire aimed
      to investigate patients' prioritization of possible research targets focused on
      solving these problems. RESULTS: The focus groups produced a wide range of
      problems, including those related to health-care organization, social
      environment, therapy and costs. In terms of research prioritization, patients
      focused primarily on biomedical issues, particularly aetiology, co-morbidity and
      effective medication. CONCLUSIONS: The consultation procedure successfully
      elicited patients' research priorities including the underlying arguments. Our
      results indicate that asthma and COPD patients are capable of research
      prioritization in a well-argued way and that they highly value biomedical
      research. Furthermore, as they prioritized some research topics that are not
      covered by current Dutch research programmes, we argue that patient participation
      can broaden research agenda setting.

PMID- 16098160
TI  - Nurse prescribers: who are they and how do they perceive their role?
AB  - AIMS: This paper reports a study to elicit background data from recently
      qualified nurse prescribers and explore aspects of their work. BACKGROUND: Nurse
      prescribing has been introduced quite recently in the United Kingdom. Although a
      certain amount of information is available about the characteristics of nurse
      prescribers, relatively little is known about their professional backgrounds,
      their reasons for choosing to become nurse prescribers and their perceptions of
      their emerging role. More information is needed to inform the selection,
      education and support of nurse prescribers. METHOD: All nurses who undertook a
      nurse prescribing course in one university in the West Midlands during 2003-2004
      were invited to participate in the study. A 40-item questionnaire was used to
      gather data on demographics, expectations of nurse prescribing, personal and
      professional development and perceived education needs. FINDINGS: Respondents
      considered that, despite initial problems, the nurse prescribing initiative would
      ultimately prove to be a cornerstone of improved service delivery for service
      users. The majority of nurses were already heavily involved in prescribing 'by
      proxy' and the course merely formalized what they were currently doing.
      Potentially, prescribing could advance the professional development of nurses,
      improve communication between professionals and patients, and make the experience
      of patients more beneficial. However, some concerns were expressed about how
      supportive the current climate in health care could be, given the multiple
      demands on time and energy required by so many other innovations. CONCLUSIONS:
      Respondents appeared balanced in their perceptions of this innovation and what it
      could realistically achieve. They were not indifferent to the many short and long
      term problems that need to be resolved before it can be claimed to have become
      embedded in practice. The success of non-medical prescribing may depend on
      organizational support, coupled with a robust continuing professional development
      strategy for all nurse prescribers.

PMID- 16098156
TI  - Patient-centred improvements in health-care built environments: perspectives and
      design indicators.
AB  - OBJECTIVE: To explore patients' perceptions of health-care built environments, to
      assess how they perceived health-care built facilities and designs. To develop a
      set of patient-centred indicators by which to appraise future health-care
      designs. DESIGN: Qualitative and quantitative methodologies, including futures
      group conferencing, autophotographic study, novice-expert exchanges and a
      questionnaire survey of a representative sample of past patients. SETTING AND
      PARTICIPANTS: The research was carried out at Salford Royal Hospitals NHS Trust
      (SRHT), Greater Manchester, UK, selected for the study because of planned
      comprehensive redevelopment based on the new NHS vision for hospital care and
      service delivery for the 21st century. Participants included 35 patients who took
      part in an autophotographic study, eight focus groups engaged in futures
      conferencing, a sample of past inpatients from the previous 12 months that
      returned 785 completed postal questionnaires. RESULTS: The futures group provided
      suggestions for radical improvements which were categorized into transport
      issues; accessibility and mobility; ground and landscape designs; social and
      public spaces; homeliness and assurance; cultural diversity; safety and security;
      personal space and access to outside. Patients' autophotographic study centred
      on: the quality of the ward design, human interactions, the state and quality of
      personal space, and facilities for recreation and leisure. The novices'
      suggestions were organized into categories of elemental factors representing
      patient-friendly designs. Experts from the architectural and surveying
      professions and staff at SRHT in turn considered these categories and respective
      subsets of factors. They agreed with the novices in terms of the headings but
      differed in prioritizing the elemental factors. The questionnaire survey of past
      patients provided opinions about ward designs that varied according to where they
      stayed, single room, bay ward or long open ward. The main concerns were
      limitation of private space around the bed area, supportive of privacy and
      dignity, ward noise and other disturbances. CONCLUSIONS: Patients perceived
      sustainable health-care environments to be supportive of their health and
      recovery. The design indicators developed from their perspectives and from their
      considerations for improvements to the health-care built environment were based
      on their visions of the role of the health-care facilities. These were homely
      environments that supported normal lifestyle and family functioning and designs
      that were supportive of accessibility and travel movements through transitional
      spaces.

PMID- 16098161
TI  - Needlestick and sharps injuries among nursing students.
AB  - AIMS: This paper reports the first investigation of the prevalence and nature of
      needlestick injuries among Australian nursing students. BACKGROUND: Needlestick
      and sharps injuries are the most efficient method of transmitting blood-borne
      pathogens between patients and healthcare staff. Although nurses are known to be
      a high-risk subgroup for these events, nursing students may be at even greater
      risk due to their limited clinical experience. Despite this fact, the
      epidemiology of needlestick and sharps injuries among nursing students has not
      been clearly elucidated in Australia. METHODS: A questionnaire-based methodology
      adapted from other international investigations was conducted among nursing
      students. We recruited a complete cross-section of students from a large
      university nursing school in North Queensland, Australia, in March 2004, and
      analysed needlestick and sharps events as a percentage of all students and also
      as a proportion of all cases. Risk factors were evaluated using logistic
      regression. RESULTS: From a group of 319 students, 274 successfully completed
      questionnaires were obtained (overall response rate 85.9%). A total of 38
      students (13.9%) reported a needlestick or sharps injury during the previous 12
      months. By causative item, 6.2% of students had been injured by a normal hollow
      bore syringe needle, 3.6% by a glass item and 3.3% by an insulin syringe needle.
      Regarding prior usage, 81.6% of all injuring items were unused, 15.8% had been
      used on a patient and the status of 2.6% was unknown. Most needlestick injuries
      occurred either in the nursing laboratory (45%) or the teaching hospital (37%).
      Opening the needle cap was the most common causative event (28% of all cases). A
      total of 39.5% of needlestick injuries were not reported. The main reason for non
      reporting was that the item was unused (42%). Logistic regression analysis
      revealed that students in the third year were 14.8 times more likely to have
      experienced a needlestick injury than their counterparts in other years (odds
      ratio 14.8, 95% confidence interval 5.2-50.3, P < 0.01). These injury rates were
      higher among Australian nursing students than in other international studies.
      CONCLUSIONS: Although hepatitis B vaccination coverage among the students was
      excellent, it is important that the principles of infection-control training and
      reporting of all needlestick and sharps continue to be emphasized throughout
      undergraduate nursing education.

PMID- 16098162
TI  - Parent or nurse? The experience of being the parent of a technology-dependent
      child.
AB  - AIMS: This paper reports a study exploring parents' experiences of caring for a
      child who is dependent on medical technology, and in particular of performing
      clinical procedures on their own children. BACKGROUND: A group of children with a
      continuing need for the support of medical technology have emerged in community
      settings as a result of medical advances and government policies. Caring for
      these children has a significant social and emotional impact on parents, because
      of their specialized and intensive care needs. Obtaining appropriate and
      coordinated home support services is problematic. METHODS: Grounded theory
      techniques were used, and in-depth interviews were conducted with the parents of
      24 children. FINDINGS: Parents' accounts revealed that their constructions of
      parenting were shaped by the nature of their role in caring for their child and
      by the transformation of their homes by medical equipment and personnel. They
      described themselves as having a role that had both parenting and nursing
      dimensions. Parents managed this tension and defined their role and relationship
      to their child to be primarily one of parenting by differentiating parental care
      giving and its underpinning knowledge from that of professionals, particularly
      nurses. CONCLUSIONS: Parenting a technology-dependent child alters the meaning of
      parenting. Professionals need to recognize that providing care has a substantial
      emotional dimension for parents, and that they need opportunities to discuss
      their feelings about caregiving and what it means for their parenting identity
      and their relationship with their child. A key professional nursing role will be
      giving emotional support and supporting parents' coping strategies. Parents'
      perceptions of nurses raise questions about whether nurses' caregiving is
      individualized to the needs of the child and family, and whether parental
      expertise is recognized.

PMID- 16098163
TI  - Evidence-based practice among Danish cardiac nurses: a national survey.
AB  - AIMS: This paper presents a survey of evidence-based practice among cardiac
      nurses exploring nurses' attitudes towards evidence-based practice and the types
      of knowledge they employ in clinical practice. BACKGROUND: Research utilization
      and evidence-based practice are required at hospitals around the world, although
      the definition of evidence-based practice is still unclear. An ongoing debate
      exists about the sources of knowledge and the hierarchy of research evidence in
      clinical practice, and nursing research has been threatened by the dominance of
      randomized controlled trials. Evidence-based practice has been described as a new
      paradigm, which promotes patient-centred care by integrating external evidence
      and patient preferences. METHODS: The study was a cross-sectional survey with a
      descriptive and comparative design, using self-administered postal
      questionnaires. The questionnaires were sent to 33 head nurses and 51 bedside
      nurses representing one or two units in each cardiac department in Denmark (n =
      28). The final response rate was 81%. The study was carried out in 2004. RESULTS:
      Respondents had a positive attitude towards evidence-based practice, although
      they relied upon personal clinical experience. Head nurses were statistically
      significantly more familiar with the concept of evidence-based practice than
      bedside nurses, and read scientific journals more frequently. Introductory
      courses to evidence-based practice are rare and seldom mandatory, and the data
      suggest that respondents lacked knowledge of the finer points of evidence-based
      practice and equated the concept with research utilization. CONCLUSIONS: Barriers
      to evidence-based practice are inadequate education, unfamiliarity with English,
      and low organizational position. Facilitators include the implementation of
      guidelines, provision of continuing education, and an increase in the
      accountability of bedside nurses.

PMID- 16098164
TI  - Accident and Emergency nurses' attitudes towards health promotion.
AB  - AIM: This paper presents a study exploring Accident and Emergency nurses'
      attitudes towards health promotion. BACKGROUND: Much has been written about
      nurses and health promotion. Research has focused mainly on community nurses,
      less on nurses working in acute hospital settings, and apparently not at all on
      those working in Accident and Emergency units. METHODS: Q methodology, a
      technique for extracting subjective opinions, was used. Eleven nurses working in
      Accident and Emergency departments completed 33-item Q-sorts and wrote personal
      definitions of health promotion. Based on published literature in the field, the
      Q sample was structured with reference to nurses' attitudes as they related to
      health promotion. Factor analysis was performed on the data, and the resulting
      factors were interpreted. The data were collected in 2003. RESULTS: Three
      alternative constructions emerged from the data, representing three alternate
      views about health promotion. The most widely held opinion (representing nine of
      the 11 nurses) was a positive view of health promotion and the nurses' role in
      health promotion in Accident and Emergency environments. CONCLUSIONS: It is not
      possible to generalize the findings of this study due to the small number of
      participants. However, their knowledge of, and commitment to, health promotion is
      encouraging. Recommendations for practice are that there is continued and
      increased post-registration education in health promotion for nurses and
      continuing exploration of the hospital nurses' health promotion role. Further
      research is needed to explore nurses' perceptions of barriers to effective health
      promotion and nurses' health promotion activities in Accident and Emergency
      environments.

PMID- 16098166
TI  - Fieldwork in nursing research: positionality, practicalities and predicaments.
AB  - AIMS: This paper draws on the literature to explore some of the issues of concern
      to nurses undertaking fieldwork in contemporary healthcare settings. BACKGROUND:
      The emergence of poststructuralist and postmodern perspectives has raised
      questions about ethnographic approaches, and problematized the role of
      researchers in the construction of plausible and credible ethnographic accounts.
      As a practice discipline, nursing needs to negotiate a thorny path between
      methodological purity and practical application, with nurse researchers required
      to take account of both philosophical and pragmatic concerns. DISCUSSION: There
      is general agreement that researching with an individual or group rather than
      researching on an individual or group is the more effective way to approach
      fieldwork. Feminist writers appear to have dealt with this issue best, advocating
      intimacy, self-disclosure, and reciprocity in encounters with research
      participants. The duality of the nurse researcher role; power and politics and
      the moral implications of fieldwork are acknowledged as factors influencing
      nurses in the planning and conduct of fieldwork. Nurses as researchers may be
      better equipped than other social researchers to deal with contingencies in the
      field. CONCLUSIONS: Laying the epistemological ground for the participant
      observer role during fieldwork and understanding its impact on the resultant
      ethnographic account is essential to methodological rigour in field research.
      Consideration of some of the practicalities and predicaments experienced by
      nurses as researchers when conducting fieldwork prior to going out into the field
      is an important research strategy and will facilitate methodological potency.

PMID- 16098165
TI  - Fever: a concept analysis.
AB  - AIM: The purpose of this paper is to critically analyse the current state of the
      science literature in order to develop an accurate conception of fever.
      RATIONALE: The measurement of body temperature and treatment of fever have long
      been considered to be within the domain of nursing practice. What body
      temperature constitutes 'fever', however, is often not clear from nursing
      protocols or the literature. METHODS: Literature for this concept analysis was
      obtained by computerized searches of PubMed, CINAHL and BIOSYS for the years 1980
      2004. Additional sources were obtained after reviewing the bibliographies of the
      literature identified by the initial search. The Wilsonian method of concept
      analysis provided the framework for the analysis. FINDINGS: Fever has
      characteristically been recognized as a cardinal sign of illness and has
      traditionally had negative connotations for patient well-being. Substantive
      advances over the past 20 years in immunology and neurophysiology have expanded
      understanding of the process of fever. This new knowledge has shifted the
      perception of fever as part of the acute-phase response to one of an adaptive
      nature. This knowledge has yet to be fully translated into changes in the fever
      management practices of nurses. CONCLUSIONS: Consistent usage of terminology in
      relation to fever should lead to improved and evidence-based care for patients,
      and to fever management practices consistent with current research. It is
      important to use clear language about fever and hyperthermia in discussions and
      documentation between nurses and among disciplines. By creating clarity in our
      language, we may help to achieve praxis.

PMID- 16098167
TI  - Room for improvement? Reporting response rates and recruitment in nursing
      research in the past decade.
AB  - AIMS: This paper reports an analysis of recruitment and response rates in
      published nursing research in three peer reviewed nursing journals in 2002. We
      wished to establish if the deficits in reporting nursing research identified a
      decade earlier had been addressed. BACKGROUND: This analysis was informed by our
      personal experiences of research which produced widely differing response rates.
      An examination of the literature revealed a lack of consensus on desirable
      response rates in nursing research. Previous analyses have shown deficits in
      describing participants, sampling methods and reporting recruitment. METHODS:
      Papers reporting empirical research in three nursing journals in 2002 were
      reviewed in terms of a number of variables including research methodology,
      respondent type, recruitment method, response rate, location, and data collection
      method. Nominal coding was used as necessary. Data were analysed using the
      Statistical Package for Social Sciences and a variety of descriptive statistics
      were employed. RESULTS: Half of the papers did not report a response rate. Of
      those which did, over three-quarters of both qualitative and quantitative studies
      had response rates of 60% or more. Research conducted in hospital and educational
      settings produced higher response rates than those in community settings. Studies
      with response rates of less than 60% did not always refer to their rates in the
      study limitations, and low response rates do not appear to be a barrier to
      publication. CONCLUSION: Reporting of sampling, recruitment and response rates in
      nursing research must be improved to support nursings' claim to be an evidence
      based profession and to underpin clinical governance requirements. Only through
      improvements in the quality of nursing research publications can knowledge be
      extended and a better-informed research community be created.

PMID- 16098168
TI  - Breaking traditions: sexual health and ethnicity in nursing research: a
      literature review.
AB  - AIM: The aim of this paper is to explore some reasons for the lack of focus on
      ethnicity and sexual health in nursing research, and suggest ways to advance the
      nursing evidence-base required for practice development. BACKGROUND: The United
      Kingdom National Strategy for Sexual Health and human immunodeficiency virus
      published in July 2001 highlighted the continued rise in sexual ill health
      amongst minority ethnic groups. In order to improve sexual health, research
      evidence is needed explain why particular ethnic groups appear to be at greater
      risk of sexual ill health. The Strategy identified nurses as key to bringing
      about improvements in sexual health. Nursing research includes many studies
      exploring links between ethnicity and health. However, with the exception of
      extensive work on human immunodeficiency virus/acquired immunodeficiency syndrome
      as a specific disease, nursing research into ethnicity has not systematically
      included sexual health. METHODS: Literature searches were conducted using the
      BIDS database, World Wide Web and United Kingdom Department of health website
      between June 2000 and August 2003. Papers written in English incorporating the
      keywords 'sexual health', 'sexually transmitted infection' and 'health and
      ethnicity' in the title or abstract were selected for review. FINDINGS: Nursing
      research into the association between sexual health and ethnicity is rare. It has
      been hampered by a variety of political and social constraints concerning the
      nature of sexual health practice in nursing, researching sexual health, and
      researching ethnicity and health. The result is a dearth of research evidence to
      support the development of sexual health practice and the education of healthcare
      professionals to underpin care of minority ethnic clients. CONCLUSIONS: Barriers
      to researching ethnicity and sexual health by nurses must be addressed through
      nursing education and practice. Without this, a detailed evidence base will fail
      to materialize and healthcare practices to implement the priorities to improve
      sexual health in minority ethnic communities will remain undeveloped.

PMID- 16098169
TI  - Informational and emotional needs of long-term survivors of breast cancer.
AB  - AIMS: This paper presents a review of the informational and emotional needs of
      long-term breast cancer survivors, with particular attention to the different
      needs of women according to their age and to critiquing healthcare provision to
      these women. BACKGROUND: Women with a history of breast cancer are the largest
      group of cancer survivors. While they may be disease-free, their cancer diagnosis
      has ongoing physical and psychosocial implications for their lives and well
      being. METHODS: A literature search for the period 1985 to March 2004 was
      undertaken using the CINAHL, MEDLINE, CANCERLIT, PubMed and CUIDEN databases and
      the keywords long-term, breast cancer survivors, needs and social support. Hand
      searching was also done, and reference lists of papers were examined for relevant
      studies. RESULTS: Survivors of breast cancer continue to experience informational
      and emotional needs during their long-term survivorship, and variation in the
      amount and type of support required is age-related. However, women's needs are
      often unmet by oncology teams and they have to find other sources of support,
      such as self-help groups. Thus, ongoing care is required after completion of
      medical treatment, and nurses have a significant contribution to make here.
      CONCLUSIONS: Nursing research on long-term breast cancer survivorship is limited.
      Future studies need to investigate the unmet needs of long-term survivors of
      breast cancer and, specifically, explore the kind of support women would like to
      receive from oncology teams, and particularly from breast cancer nurses.

PMID- 16098170
TI  - Specialist educational intervention for mental health nursing staff: delivery,
      content and personal impact.
AB  - AIM: This paper reports a study to ascertain the views of acute ward-based mental
      health nursing staff on the delivery, content and personal impact of an
      innovative 18-day, whole team educational intervention in acute mental health
      care. BACKGROUND: There are grave concerns internationally about the quality of
      inpatient mental health care for people with acute psychiatric problems.
      Educational courses are needed to improve these services. However, existing
      schemes are often selective, hard to access and limited to developing highly
      specialist skills for senior nurses. They have also been criticized for making no
      difference to clinical practice. There is little evidence to guide the
      development of these or alternative team-based courses. METHOD: Qualitative data
      were collected over a 6-week period using 12 focus group interviews and
      individual questionnaires. RESULTS: Four themes were identified. The joint
      education of nursing staff from different organizations was welcomed and reduced
      feelings of ward isolation. Mixing qualified and unqualified staff was not
      regarded positively. In terms of course content and learning themes, unqualified
      staff were more likely to report positive learning outcomes for knowledge,
      skills, attitude, morale and personal development; qualified nurses were more
      likely to indicate positive outcomes in anonymized data from questionnaires than
      from focus groups. Both groups reported little chance of knowledge implementation
      without changes in the organization of care. CONCLUSION: Whilst it may be
      desirable to educate whole nursing teams, more benefit might be gained from
      shared education between several organizations and separating the education of
      qualified and unqualified staff before combining these groups in team education.
      Participants remained pessimistic about their chances of implementing new
      knowledge and skills in current acute inpatient mental health environments.

PMID- 16098171
TI  - A response to S. Hoskins, M. Coleman & D. McNeely (2005) Stress in carers of
      individuals with dementia and Community Mental Health Teams: an uncontrolled
      evaluation study. Journal of Advanced Nursing 50(3), 325-333.

PMID- 16098177
TI  - Abstracts from the 15th Annual Meeting of the German Society for Cytometry in
      collaboration with the Centre for Environmental Research Leipzig-Halle GmbH.
      October 19-22, 2005. Leipzig, Germany.

PMID- 16098176
TI  - Cytomics, the human cytome project and systems biology: top-down resolution of
      the molecular biocomplexity of organisms by single cell analysis.
AB  - A large amount of structural and functional information is obtained by molecular
      cell phenotype analysis of tissues, organs and organisms at the single cell level
      by image or flow cytometry in combination with bioinformatic knowledge extraction
      (cytomics) concerning nuclei acids, proteins and metabolites (cellular genomics,
      proteomics and metabolomics) as well as cell function parameters like
      intracellular pH, transmembrane potentials or ion gradients. In addition,
      differential molecular cell phenotypes between diseased and healthy cells provide
      molecular data patterns for (i) predictive medicine by cytomics or for (ii) drug
      discovery purposes using reverse engineering of the data patterns by biomedical
      cell systems biology. Molecular pathways can be explored in this way including
      the detection of suitable target molecules, without detailed a priori knowledge
      of specific disease mechanisms. This is useful during the analysis of complex
      diseases such as infections, allergies, rheumatoid diseases, diabetes or
      malignancies. The top-down approach reaching from single cell heterogeneity in
      cell systems and tissues down to the molecular level seems suitable for a human
      cytome project to systematically explore the molecular biocomplexity of human
      organisms. The analysis of already existing data from scientific studies or
      routine diagnostic procedures will be of immediate value in clinical medicine,
      for example as personalized therapy by cytomics.

PMID- 16098181
TI  - Cell proliferation rates in an artificial tissue-engineered environment.
AB  - Worldwide, and particularly in Europe, Japan and the USA, cardiovascular disease
      is a major killer. It can be treated using tissue or organ transplant surgery,
      but donor organs may be scarce. Tissue engineering is the integration of
      engineering principles and biology to produce satisfactory synthetic replacement
      body parts, using viable cells in a suitable matrix, for regenerative medicine.
      The aim of this study was to measure and compare cell proliferation kinetics
      after different time intervals of myofibroblasts in a synthetic matrix, thus to
      be able to deduce the period that a transplanted-cell population can be expected
      to survive in a tissue-engineered environment. Porcine aortic wall cells were
      grown in a porous sponge scaffold, that later could be fashioned into aortic or
      heart valve substitutes. Freshly acquired cells were seeded on identical sponges
      and were grown under normal culture conditions for a period of 4 weeks. Seeding
      concentration was a million cells per sponge. Cells progressively populated the
      sponges, both covering the surface and infiltrating the depth of the matrix, via
      sponge pores. Samples were taken at 1 week and at 4 weeks, and the rate of cell
      proliferation was determined by the metaphase arrest technique. Specimens were
      also taken for light and electron microscopy to determine whether these
      transplanted cells were capable of synthesizing their own extracellular matrix.

PMID- 16098182
TI  - Cytometric assessment of DNA damage in relation to cell cycle phase and
      apoptosis.
AB  - Reviewed are the methods aimed to detect DNA damage in individual cells, estimate
      its extent and relate it to cell cycle phase and induction of apoptosis. They
      include the assays that reveal DNA fragmentation during apoptosis, as well as DNA
      damage induced by genotoxic agents. DNA fragmentation that occurs in the course
      of apoptosis is detected by selective extraction of degraded DNA. DNA in
      chromatin of apoptotic cells shows also increased propensity to undergo
      denaturation. The most common assay of DNA fragmentation relies on labelling DNA
      strand breaks with fluorochrome-tagged deoxynucleotides. The induction of double
      strand DNA breaks (DSBs) by genotoxic agents provides a signal for histone H2AX
      phosphorylation on Ser139; the phosphorylated H2AX is named gammaH2AX. Also, ATM
      kinase is activated through its autophosphorylation on Ser1981.
      Immunocytochemical detection of gammaH2AX and/or ATM-Ser1981(P) are sensitive
      probes to reveal induction of DSBs. When used concurrently with analysis of
      cellular DNA content and caspase-3 activation, they allow one to correlate the
      extent of DNA damage with the cell cycle phase and with activation of the
      apoptotic pathway. The presented data reveal cell cycle phase-specific patterns
      of H2AX phosphorylation and ATM autophosphorylation in response to induction of
      DSBs by ionizing radiation, topoisomerase I and II inhibitors and carcinogens.
      Detection of DNA damage in tumour cells during radio- or chemotherapy may provide
      an early marker predictive of response to treatment.

PMID- 16098183
TI  - Production of stem cells with embryonic characteristics from human umbilical cord
      blood.
AB  - When will embryonic stem cells reach the clinic? The answer is simple -- not
      soon! To produce large quantities of homogeneous tissue for transplantation,
      without feeder layers, and with the appropriate recipient's immunological
      phenotype, is a significant scientific hindrance, although adult stem (ADS) cells
      provide an alternative, more ethically acceptable, source. The annual global 100
      million human birth rate proposes umbilical cord blood (UCB) as the largest
      untouched stem cell source, with advantages of naive immune status and relatively
      unshortened telomere length. Here, we report the world's first reproducible
      production of cells expressing embryonic stem cell markers, - cord-blood-derived
      embryonic-like stem cells (CBEs). UCB, after elective birth by Caesarean section,
      has been separated by sequential immunomagnetic removal of nucleate granulocytes,
      erythrocytes and haemopoietic myeloid/lymphoid progenitors. After 7 days of high
      density culture in microflasks, (10(5) cells/ml, IMDM, FCS 10%, thrombopoietin 10
      ng/ml, flt3-ligand 50 ng/ml, c-kit ligand 20 ng/ml). CBE colonies formed adherent
      to the substrata; these were maintained for 6 weeks, then were subcultured and
      continued for a minimum 13 weeks. CBEs were positive for TRA-1-60, TRA-1-81, SSEA
      4, SSEA-3 and Oct-4, but not SSEA-1, indicative of restriction in the human stem
      cell compartment. The CBEs were also microgravity--bioreactor cultured with
      hepatocyte growth medium (IMDM, FCS 10%, HGF 20 ng/ml, bFGF 10 ng/ml, EGF 10
      ng/ml, c-kit ligand 10 ng/ml). After 4 weeks the cells were found to express
      characteristic hepatic markers, cytokeratin-18, alpha-foetoprotein and albumin.
      Thus, such CBEs are a viable human alternative from embryonic stem cells for stem
      cell research, without ethical constraint and with potential for clinical
      applications.

PMID- 16098184
TI  - Pericellular oxygen depletion during ordinary tissue culturing, measured with
      oxygen microsensors.
AB  - Recent research has found important differences in oxygen tension in proximity to
      certain mammalian cells when grown in culture. Oxygen has a low diffusion rate
      through cell culture media, thus, as a result of normal respiration, a decrease
      in oxygen tension develops close to the cells. Therefore, for the purpose of
      standardization and optimization, it is important to monitor pericellular oxygen
      tension and cell oxygen consumption. Here, we describe an integrated oxygen
      microsensor and recording system that allows measurement of oxygen concentration
      profiles in vertical transects through a 1.6-mm deep, stagnant, medium layer
      covering a cell culture. The measurement set-up reveals that, when confluent, a
      conventional culture of adherent cells, although exposed to the constant oxygen
      tension of ambient air, may experience pericellular oxygen tensions below the
      level required to sustain full oxidative metabolism. Depletions reported are even
      more prominent and potentially aggravating when the cell culture is incubated at
      reduced oxygen tensions (down to around 4% oxygen). Our results demonstrate that,
      if the pericellular oxygen tension is not measured, it is impossible to relate in
      vitro culture results (for example, gene expression to the oxygen tension
      experienced by the cell), as this concentration may deviate very substantially
      from the oxygen concentration recorded in the gas phase.

PMID- 16098185
TI  - Mitochondrial calcium signalling in cell death.
AB  - The development of targeted probes (based on the molecular engineering of
      luminescent or fluorescent proteins) has allowed the specific measurement of
      [Ca2+] in intracellular organelles or cytoplasmic subdomains. This approach gave
      novel information on different aspects of cellular Ca2+ homeostasis. Regarding
      mitochondria, it was possible to demonstrate that, upon physiological stimulation
      of cells, Ca2+ is rapidly accumulated in the matrix. We will discuss the basic
      characteristics of this process, its role in modulating physiological and
      pathological events, such as the regulation of aerobic metabolism and the
      induction of cell death, and new insight into the regulatory mechanisms operating
      in vivo.

PMID- 16098186
TI  - PA700, the regulatory complex of the 26S proteasome, interferes with alpha
      synuclein assembly.
AB  - Parkinson's disease is characterized by the loss of dopaminergic neurons in the
      nigrostriatal pathway accompanied by the presence of intracellular cytoplasmic
      inclusions, termed Lewy bodies. Fibrillized alpha-synuclein forms the major
      component of Lewy bodies. We reported a specific interaction between rat alpha
      synuclein and tat binding protein 1, a subunit of PA700, the regulatory complex
      of the 26S proteasome. It has been demonstrated that PA700 prevents the
      aggregation of misfolded, nonubiquinated substrates. In this study, we examine
      the effect of PA700 on the aggregation of wild-type and A53T mutant alpha
      synuclein. PA700 inhibits both wild-type and A53T alpha-synuclein fibril
      formation as measured by Thioflavin T fluorescence. Using size exclusion
      chromatography, we present evidence for a stable PA700-alpha-synuclein complex.
      Sedimentation analyses reveal that PA700 sequesters alpha-synuclein in an
      assembly incompetent form. Analysis of the morphology of wild-type and A53T alpha
      synuclein aggregates during the course of fibrillization by electron microscopy
      demonstrate the formation of amyloid-like fibrils. Secondary structure analyses
      of wild-type and A53T alpha-synuclein assembled in the presence of PA700 revealed
      a decrease in the overall amount of assembled alpha-synuclein with no significant
      change in protein conformation. Thus, PA700 acts on alpha-synuclein assembly and
      not on the structure of fibrils. We hypothesize that PA700 sequesters alpha
      synuclein oligomeric species that are the precursors of the fibrillar form of the
      protein, thus preventing its assembly into fibrils.

PMID- 16098187
TI  - Biochemical network models simplified by balanced truncation.
AB  - Modelling of biochemical systems usually focuses on certain pathways, while the
      concentrations of so-called external metabolites are considered fixed. This
      approximation ignores feedback loops mediated by the environment, that is, via
      external metabolites and reactions. To achieve a more realistic, dynamic
      description that is still numerically efficient, we propose a new methodology:
      the basic idea is to describe the environment by a linear effective model of
      adjustable dimensionality. In particular, we (a) split the entire model into a
      subsystem and its environment, (b) linearize the environment model around a
      steady state, and (c) reduce its dimensionality by balanced truncation, an
      established method for large-scale model reduction. The reduced variables
      describe the dynamic modes in the environment that dominate its interaction with
      the subsystem. We compute metabolic response coefficients that account for
      complexity-reduced dynamics of the environment. Our simulations show that a
      dynamic environment model can improve the simulation results considerably, even
      if the environment model has been drastically reduced and if its kinetic
      parameters are only approximately known. The speed-up in computation gained by
      model reduction may become vital for parameter estimation in large cell models.

PMID- 16098188
TI  - A second novel dye-linked L-proline dehydrogenase complex is present in the
      hyperthermophilic archaeon Pyrococcus horikoshii OT-3.
AB  - Two distinguishable activity bands for dye-linked l-proline dehydrogenase (PDH1
      and PDH2) were detected when crude extract of the hyperthermophilic archaeon
      Pyrococcus horikoshii OT-3 was run on a polyacrylamide gel. After purification,
      PDH1 was found to be composed of two different subunits with molecular masses of
      56 and 43 kDa, whereas PDH2 was composed of four different subunits with
      molecular masses of 52, 46, 20 and 8 kDa. The native molecular masses of PDH1 and
      PDH2 were 440 and 101 kDa, respectively, indicating that PDH1 has an alpha4beta4
      structure, while PDH2 has an alphabetagammadelta structure. PDH2 was found to be
      similar to the dye-linked l-proline dehydrogenase complex from Thermococcus
      profundus, but PDH1 is a different type of enzyme. After production of the enzyme
      in Escherichia coli, high-performance liquid chromatography showed the PDH1
      complex to contain the flavins FMN and FAD as well as ATP. Gene expression and
      biochemical analyses of each subunit revealed that the beta subunit bound FAD and
      exhibited proline dehydrogenase activity, while the alpha subunit bound ATP, but
      unlike the corresponding subunit in the T. profundus enzyme, it exhibited neither
      proline dehydrogenase nor NADH dehydrogenase activity. FMN was not bound to
      either subunit, suggesting it is situated at the interface between the alpha and
      beta subunits. A comparison of the amino-acid sequences showed that the ADP
      binding motif in the alpha subunit of PDH1 clearly differs from that in the alpha
      subunit of PDH2. It thus appears that a second novel dye-linked l-proline
      dehydrogenase complex is produced in P. horikoshii.

PMID- 16098189
TI  - Molecular dynamics structures of peptide nucleic acid x DNA hybrid in the wild
      type and mutated alleles of Ki-ras proto-oncogene--stereochemical rationale for
      the low affinity of PNA in the presence of an AC mismatch.
AB  - The low affinity of peptide nucleic acid (PNA) to hybridize with DNA in the
      presence of a mismatch endows PNA with a high degree of discriminatory capacity
      that has been exploited in therapeutics for the selective inhibition of the
      expression of point-mutated genes. To obtain a structural basis for this
      intriguing property, molecular dynamics simulations are carried out on PNA x DNA
      duplexes formed at the Ki-ras proto-oncogene, comprising the point-mutated (GAT),
      and the corresponding wild-type (GGT) codon 12. The designed PNA forms an A...C
      mismatch with the wild-type sequence and a perfect A...T pair with the point
      mutated sequence. Results show that large movements in the pyrimidine base of the
      A...C mismatch cause loss of stacking, especially with its penultimate base,
      concomitant with a variable mismatch hydrogen bond, including its occasional
      absence. These, in turn, bring about dynamic water interactions in the vicinity
      of the mismatch. Enthalpy loss and the disproportionate entropy gain associated
      with these are implicated as the factors contributing to the increase in free
      energy and diminished stability of PNA x DNA duplex with the A...C mismatch.
      Absence of these in the isosequential DNA duplex, notwithstanding the A...C
      mismatch, is attributed to the differences in topology of PNA x DNA vis-a-vis DNA
      duplexes. It is speculated that similar effects might be responsible for the
      reduced stability observed in PNA x DNA duplexes containing other base pair
      mismatches, and also in mismatch containing PNA x DNA duplexes.

PMID- 16098190
TI  - Quantitative analysis of ultrasensitive responses.
AB  - Ultrasensitive responses are common in cellular information transfer because they
      allow cells to decode extracellular stimuli in an all-or-none manner. Biochemical
      responses are usually analyzed by fitting the Hill equation, and the estimated
      Hill coefficient is taken as a measure of sensitivity. However, this approach is
      not appropriate if the response under consideration significantly deviates from
      the best-fit Hill equation. In addition, Hill coefficients greater than unity do
      not necessarily imply ultrasensitive behaviour if basal activation is
      significant. In order to circumvent these problems we propose a general method
      for the quantitative analysis of sensitivity, the relative amplification plot,
      which is based on the response coefficient defined in metabolic control analysis.
      To quantify sensitivity globally (i.e. over the whole stimulus range) we
      introduce the integral-based relative amplification coefficient. Our relative
      amplification approach can easily be extended to monotonically decreasing, bell
      shaped or nonsaturated responses.

PMID- 16098191
TI  - The cytochrome P450scc system opens an alternate pathway of vitamin D3
      metabolism.
AB  - We show that cytochrome P450scc (CYP11A1) in either a reconstituted system or in
      isolated adrenal mitochondria can metabolize vitamin D3. The major products of
      the reaction with reconstituted enzyme were 20-hydroxycholecalciferol and 20,22
      dihydroxycholecalciferol, with yields of 16 and 4%, respectively, of the original
      vitamin D3 substrate. Trihydroxycholecalciferol was a minor product, likely
      arising from further metabolism of dihydroxycholecalciferol. Based on NMR
      analysis and known properties of P450scc we propose that hydroxylation of vitamin
      D3 by P450scc occurs sequentially and stereospecifically with initial formation
      of 20(S)-hydroxyvitamin D3. P450scc did not metabolize 25-hydroxyvitamin D3,
      indicating that modification of C25 protected it against P450scc action. Adrenal
      mitochondria also metabolized vitamin D3 yielding 10 hydroxyderivatives, with UV
      spectra typical of vitamin D triene chromophores. Aminogluthimide inhibition
      showed that the three major metabolites, but not the others, resulted from
      P450scc action. It therefore appears that non-P450scc enzymes present in the
      adrenal cortex to some extent contribute to metabolism of vitamin D3. We conclude
      that purified P450scc in a reconstituted system or P450scc in adrenal
      mitochondria can add one hydroxyl group to vitamin D3 with subsequent
      hydroxylation being observed for reconstituted enzyme but not for adrenal
      mitochondria. Additional vitamin D3 metabolites arise from the action of other
      enzymes in adrenal mitochondria. These findings appear to define novel metabolic
      pathways involving vitamin D3 that remain to be characterized.

PMID- 16098192
TI  - Molecular and functional characterization of a novel splice variant of ANKHD1
      that lacks the KH domain and its role in cell survival and apoptosis.
AB  - Multiple ankyrin repeat motif-containing proteins play an important role in
      protein-protein interactions. ANKHD1 proteins are known to possess multiple
      ankyrin repeat domains and a single KH domain with no known function. Using yeast
      two-hybrid system analysis, we identified a novel splice variant of ANKHD1. This
      splice variant of ANKHD1, which we designated as HIV-1 Vpr-binding ankyrin repeat
      protein (VBARP), does not contain the signature KH domain, and codes for only a
      single ankyrin repeat motif. We characterized VBARP by molecular and functional
      analysis, revealing that VBARP is ubiquitously expressed in different tissues as
      well as cell lines of different lineage. In addition, blast searches indicated
      that orthologs and homologs to VBARP exist in different phyla, suggesting that
      VBARP might be evolutionarily conserved, and thus may be involved in basic
      cellular function(s). Furthermore, biochemical analysis revealed the presence of
      two VBARP isoforms coding for 69 and 49 kDa polypeptides, respectively, that are
      primarily localized in the cytoplasm. Functional analysis using short interfering
      RNA approaches indicate that this gene product is essential for cell survival
      through its regulation of caspases. Taken together, these results indicate that
      VBARP is a novel splice variant of ANKHD1 and may play a role in cellular
      apoptosis (antiapoptotic) and cell survival pathway(s).

PMID- 16098193
TI  - The A-subunit of surface-bound Shiga toxin stimulates clathrin-dependent uptake
      of the toxin.
AB  - Shiga toxin can be internalized by clathrin-dependent endocytosis in different
      cell lines, although it binds specifically to the glycosphingolipid Gb3. It has
      been demonstrated previously that the toxin can induce recruitment of the toxin
      receptor complex to clathrin-coated pits, but whether this process is
      concentration-dependent or which part of the toxin molecule is involved in this
      process, have so far been unresolved issues. In this article, we show that the
      rate of Shiga toxin uptake is dependent on the toxin concentration in several
      cell lines [HEp-2, HeLa, Vero and baby hamster kidney (BHK)], and that the
      increased rate observed at higher concentrations is strictly dependent on the
      presence of the A-subunit of cell surface-bound toxin. Surface-bound B-subunit
      has no stimulatory effect. Furthermore, this increase in toxin endocytosis is
      dependent on functional clathrin, as it did not occur in BHK cells after
      induction of antisense to clathrin heavy chain, thereby blocking clathrin
      dependent endocytosis. By immunofluorescence, we show that there is an increased
      colocalization between Alexa-labeled Shiga toxin and Cy5-labeled transferrin in
      HeLa cells upon addition of unlabeled toxin. In conclusion, the data indicate
      that the Shiga toxin A-subunit of cell surface-bound toxin stimulates clathrin
      dependent uptake of the toxin. Possible explanations for this phenomenon are
      discussed.

PMID- 16098194
TI  - Molecular cloning, expression analysis and functional confirmation of ecdysone
      receptor and ultraspiracle from the Colorado potato beetle Leptinotarsa
      decemlineata.
AB  - cDNA cloning of ecdysone receptor (EcR) and ultraspiracle (USP) of the
      coleopteran Colorado potato beetle Leptinotarsa decemlineata (LdEcR and LdUSP)
      was conducted. Amino-acid sequences of the proteins deduced from cDNA sequences
      showed striking homology to those of other insects, especially the coleopteran
      yellow mealworm Tenebrio molitor. Northern hybridization analysis showed a 12.4
      kb message for the LdEcR A-isoform, a 10.5-kb message for the LdEcR B1-isoform
      and a 5.7-kb message for the LdUSP, in fat body, gut, integument, testis and
      ovaries. In developmental profile studies, expression of both the LdEcR and LdUSP
      transcript in integument changed dramatically. In gel mobility shift assays, in
      vitro translated LdEcR alone bound weakly to the pal1 ecdysone response element,
      although LdUSP alone did not, and this binding was dramatically enhanced by the
      addition of LdUSP. LdEcR/LdUSP complex also showed significant binding to an
      ecdysone agonist, ponasterone A (K(D) = 2.8 nm), while LdEcR alone showed only
      weak binding (K(D) = 73.4 nm), and LdUSP alone did not show any binding. The
      receptor-binding affinity of various ecdysone agonists to LdEcR/LdUSP was not
      correlated to their larvicidal activity to L. decemlineata. From these results,
      it was suggested that multiple factors including the receptor binding affinity
      are related to the determination of the larvicidal activity of nonsteroidal
      ecdysone agonists in L. decemlineata.

PMID- 16098195
TI  - Cdc37 maintains cellular viability in Schizosaccharomyces pombe independently of
      interactions with heat-shock protein 90.
AB  - Cdc37 is a molecular chaperone that interacts with a range of clients and co
      chaperones, forming various high molecular mass complexes. Cdc37 sequence
      homology among species is low. High homology between yeast and metazoan proteins
      is restricted to the extreme N-terminal region, which is known to bind clients
      that are predominantly protein kinases. We show that despite the low homology,
      both Saccharomyces cerevisiae and human Cdc37 are able to substitute for the
      Schizosaccharomyces pombe protein in a strain deleted for the endogenous cdc37
      gene. Expression of a construct consisting of only the N-terminal domain of S.
      pombe Cdc37, lacking the postulated heat-shock protein (Hsp) 90-binding and
      homodimerization domains, can also sustain cellular viability, indicating that
      Cdc37 dimerization and interactions with the cochaperone Hsp90 may not be
      essential for Cdc37 function in S. pombe. Biochemical investigations showed that
      a small proportion of total cellular Cdc37 occurs in a high molecular mass
      complex that also contains Hsp90. These data indicate that the N-terminal domain
      of Cdc37 carries out essential functions independently of the Hsp90-binding
      domain and dimerization of the chaperone itself.

PMID- 16098196
TI  - cAMP inhibits CSF-1-stimulated tyrosine phosphorylation but augments CSF-1R
      mediated macrophage differentiation and ERK activation.
AB  - Macrophage colony stimulating factor (M-CSF) or CSF-1 controls the development of
      the macrophage lineage through its receptor tyrosine kinase, c-Fms. cAMP has been
      shown to influence proliferation and differentiation in many cell types,
      including macrophages. In addition, modulation of cellular ERK activity often
      occurs when cAMP levels are raised. We have shown previously that agents that
      increase cellular cAMP inhibited CSF-1-dependent proliferation in murine bone
      marrow-derived macrophages (BMM) which was associated with an enhanced
      extracellular signal-regulated kinase (ERK) activity. We report here that
      increasing cAMP levels, by addition of either 8-bromo cAMP (8BrcAMP) or
      prostaglandin E(1) (PGE1), can induce macrophage differentiation in M1 myeloid
      cells engineered to express the CSF-1 receptor (M1/WT cells) and can potentiate
      CSF-1-induced differentiation in the same cells. The enhanced CSF-1-dependent
      differentiation induced by raising cAMP levels correlated with enhanced ERK
      activity. Thus, elevated cAMP can promote either CSF-1-induced differentiation or
      inhibit CSF-1-induced proliferation depending on the cellular context. The
      mitogen-activated protein kinase/extracellular signal-related protein kinase
      kinase (MEK) inhibitor, PD98059, inhibited both the cAMP- and the CSF-1R
      dependent macrophage differentiation of M1/WT cells suggesting that ERK activity
      might be important for differentiation in the M1/WT cells. Surprisingly, addition
      of 8BrcAMP or PGE1 to either CSF-1-treated M1/WT or BMM cells suppressed the CSF
      1R-dependent tyrosine phosphorylation of cellular substrates, including that of
      the CSF-1R itself. It appears that there are at least two CSF-1-dependent
      pathway(s), one MEK/ERK dependent pathway and another controlling the bulk of the
      tyrosine phosphorylation, and that cAMP can modulate signalling through both of
      these pathways.

PMID- 16098197
TI  - Spectroscopic characterization of the isolated heme-bound PAS-B domain of
      neuronal PAS domain protein 2 associated with circadian rhythms.
AB  - Neuronal PAS domain protein 2 (NPAS2) is an important transcription factor
      associated with circadian rhythms. This protein forms a heterodimer with BMAL1,
      which binds to the E-box sequence to mediate circadian rhythm-regulated
      transcription. NPAS2 has two PAS domains with heme-binding sites in the N
      terminal portion. In this study, we overexpressed wild-type and His mutants of
      the PAS-B domain (residues 241-416) of mouse NPAS2 and then purified and
      characterized the isolated heme-bound proteins. Optical absorption spectra of the
      wild-type protein showed that the Fe(III), Fe(II) and Fe(II)-CO complexes are 6
      co-ordinated low-spin complexes. On the other hand, resonance Raman spectra
      indicated that both the Fe(III) and Fe(II) complexes contain mixtures of 5-co
      ordinated high-spin and 6-co-ordinated low-spin complexes. Based on inverse
      correlation between nu(Fe-CO) and nu(C-O) of the resonance Raman spectra, it
      appeared that the axial ligand trans to CO of the heme-bound PAS-B is His. Six
      His mutants (His266Ala, His289Ala, His300Ala, His302Ala, His329Ala, and
      His335Ala) were generated, and their optical absorption spectra were compared.
      The spectrum of the His335Ala mutant indicated that its Fe(III) complex is the 5
      co-ordinated high-spin complex, whereas, like the wild-type, the complexes for
      the five other His mutants were 6-co-ordinated low-spin complexes. Thus, our
      results suggest that one of the axial ligands of Fe(III) in PAS-B is His335.
      Also, binding kinetics suggest that heme binding to the PAS-B domain of NPAS2 is
      relatively weak compared with that of sperm whale myoglobin.

PMID- 16098198
TI  - The human cytomegalovirus-encoded chemokine receptor US28 induces caspase
      dependent apoptosis.
AB  - Viral subversion of apoptosis regulation plays an important role in the outcome
      of host/virus interactions. Although human cytomegalovirus (HCMV) encodes several
      immediate early (IE) antiapoptotic proteins (IE1, IE2, vMIA and vICA), no
      proapoptotic HCMV protein has yet been identified. Here we show that US28, a
      functional IE HCMV-encoded chemokine receptor, which may be involved in both
      viral dissemination and immune evasion, constitutively induces apoptosis in
      several cell types. In contrast, none of nine human cellular chemokine receptors,
      belonging to three different subfamilies, induced any significant level of
      apoptosis. US28-induced cell death involves caspase 10 and caspase 8 activation,
      but does not depend on the engagement of cell-surface death receptors of the
      tumour necrosis factor receptor/CD95 family. US28 cell-death induction is
      prevented by coexpression of C-FLIP, a protein that inhibits Fas-associated death
      domain protein (FADD)-mediated activation of caspase 10 and caspase 8, and by
      coexpression of the HCMV antiapoptotic protein IE1. The use of US28 mutants
      indicated that the DRY sequence of its third transmenbrane domain, required for
      constitutive G-protein signalling, and the US28 intracellular terminal domain
      required for constitutive US28 endocytosis, are each partially required for cell
      death induction. Thus, in HCMV-infected cells, US28 may function either as a
      chemokine receptor, a phospholipase C activator, or a proapoptotic factor,
      depending on expression levels of HCMV and/or cellular antiapoptotic proteins.

PMID- 16098199
TI  - Characterization of D-amino-acid-containing excitatory conotoxins and
      redefinition of the I-conotoxin superfamily.
AB  - Post-translational isomerization of l-amino acids to d-amino acids is a subtle
      modification, not detectable by standard techniques such as Edman sequencing or
      MS. Accurate predictions require more sequences of modified polypeptides. A 46
      amino-acid-long conotoxin, r11a, belonging to the I-superfamily was previously
      shown to have a d-Phe residue at position 44. In this report, we characterize two
      related peptides, r11b and r11c, with d-Phe and d-Leu, respectively, at the
      homologous position. Electrophysiological tests show that all three peptides
      induce repetitive activity in frog motor nerve, and epimerization of the single
      amino acid at the third position from the C-terminus attenuates the potency of
      r11a and r11b, but not that of r11c. Furthermore, r11c (but neither r11a nor
      r11b) also acts on skeletal muscle. We identified more cDNA clones encoding
      conopeptide precursors with Cys patterns similar to r11a/b/c. Although the
      predicted mature toxins have the same cysteine patterns, they belong to two
      different gene superfamilies. A potential correlation between the identity of the
      gene superfamily to which the I-conotoxin belongs and the presence or absence of
      a d-amino acid in the primary sequence is discussed. The great diversity of I
      conopeptide sequences provides a rare opportunity for defining parameters that
      may be important for this most stealthy of all post-translational modifications.
      Our results indicate that neither the chemical nature of the side chain nor the
      precise vicinal sequence around the modified residue seem to be critical, but
      there may be favored loci for isomerization to a d-amino acid.

PMID- 16098200
TI  - A novel thermostable hemoglobin from the actinobacterium Thermobifida fusca.
AB  - The gene coding for a hemoglobin-like protein (Tf-trHb) has been identified in
      the thermophilic actinobacterium Thermobifida fusca and cloned in Escherichia
      coli for overexpression. The crystal structure of the ferric, acetate-bound
      derivative, was obtained at 2.48 A resolution. The three-dimensional structure of
      Tf-trHb is similar to structures reported for the truncated hemoglobins from
      Mycobacterium tuberculosis and Bacillus subtilis in its central domain. The
      complete lack of diffraction patterns relative to the N- and C-terminal segments
      indicates that these are unstructured polypeptides chains, consistent with their
      facile cleavage in solution. The absence of internal cavities and the presence of
      two water molecules between the bound acetate ion and the protein surface suggest
      that the mode of ligand entry is similar to that of typical hemoglobins. The
      protein is characterized by higher thermostability than the similar mesophilic
      truncated hemoglobin from B. subtilis, as demonstrated by far-UV CD melting
      experiments on the cyano-met derivatives. The ligand-binding properties of Tf
      trHb, analyzed in stopped flow experiments, demonstrate that Tf-trHb is capable
      of efficient O2 binding and release between 55 and 60 degrees C, the optimal
      growth temperature for Thermobifida fusca.

PMID- 16098201
TI  - Novel brain 14-3-3 interacting proteins involved in neurodegenerative disease.
AB  - We isolated two novel 14-3-3 binding proteins using 14-3-3 zeta as bait in a
      yeast two-hybrid screen of a human brain cDNA library. One of these encoded the C
      terminus of a neural specific armadillo-repeat protein, delta-catenin (neural
      plakophilin-related arm-repeat protein or neurojungin). delta-Catenin from brain
      lysates was retained on a 14-3-3 affinity column. Mutation of serine 1072 in the
      human protein and serine 1094 in the equivalent site in the mouse homologue (in a
      consensus binding motif for 14-3-3) abolished 14-3-3 binding to delta-catenin in
      vitro and in transfected cells. delta-catenin binds to presenilin-1, encoded by
      the gene most commonly mutated in familial Alzheimer's disease. The other clone
      was identified as the insulin receptor tyrosine kinase substrate protein of 53
      kDa (IRSp53). Human IRSp53 interacts with the gene product implicated in
      dentatorubral-pallidoluysian atrophy, an autosomal recessive disorder associated
      with glutamine repeat expansion of atrophin-1.

PMID- 16098202
TI  - Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in
      relationships with tau in Alzheimer's disease brain.
AB  - The pathogenesis of formation of neurofibrillary tangles (NFTs) in Alzheimer's
      disease (AD) brains is unknown. One of the possibilities might be that
      translation of tau mRNA is aberrantly regulated in AD brains. In the current
      study, levels of various translation control elements including total and
      phosphorylated (p) forms of mammalian target of rapamycin (mTOR), eukaryotic
      initiation factor 4E binding protein 1 (4E-BP1), eukaryotic elongation factor 2
      (eEF2), and eEF2 kinase were investigated in relationship with tau in homogenates
      of the medial temporal cortex from 20 AD and 10 control brains. We found that
      levels of p-mTOR (Ser2481), and p-4E-BP1 (Thr70 and Ser65) dramatically increase
      in AD, and are positively significantly correlated with total tau and p-tau.
      Levels of p-eEF2K were significantly increased, and total eEF2 significantly
      decreased in AD, when compared to controls. The changes of p-mTOR (2481), p-4E
      BP1, and p-eEF2 were immunohistochemically confirmed to be in neurons of AD
      brains. This suggested that there are obvious abnormalities of elements related
      with translation control in AD brain and their aberrant changes may up-regulate
      the translation of tau mRNA, contributing to hyperphosphorylated tau accumulation
      in NFT-bearing neurons.

PMID- 16098203
TI  - Recombinant derivatives of the human high-mobility group protein HMGB2 mediate
      efficient nonviral gene delivery.
AB  - Certain natural peptides and proteins of mammalian origin are able to bind and
      condense plasmid DNA, a prerequisite for the formation of transfection-competent
      complexes that facilitate nonviral gene delivery. Here we have generated
      recombinant derivatives of the human high-mobility group (HMG) protein HMGB2 and
      investigated their potential as novel protein-based transfection reagents. A
      truncated form of HMGB2 encompassing amino acids 1-186 of the molecule was
      expressed in Escherichia coli at high yield. This HMGB2186 protein purified from
      bacterial lysates was able to condense plasmid DNA in a concentration-dependent
      manner, and mediated gene delivery into different established tumor cell lines
      more efficiently than poly(l-lysine). By attaching, via gene fusion, additional
      functional domains such as the HIV-1 TAT protein transduction domain (TAT(PTD)
      HMGB2186), the nuclear localization sequence of the simian virus 40 (SV40) large
      T-antigen (SV40(NLS)-HMGB2186), or the importin-beta-binding domain (IBB) of
      human importin-alpha (IBB-HMGB2186), chimeric fusion proteins were produced which
      displayed markedly improved transfection efficiency. Addition of chloroquine
      strongly enhanced gene transfer by all four HMGB2186 derivatives studied,
      indicating cellular uptake of protein-DNA complexes via endocytosis. The IBB
      HMGB2186 molecule in the presence of the endosomolytic reagent was the most
      effective. Our results show that recombinant derivatives of human HMGB2
      facilitate efficient nonviral gene delivery and may become useful reagents for
      applications in gene therapy.

PMID- 16098204
TI  - Benzamide and 4-amino 1,8 naphthalimide treatment inhibit telomerase activity by
      down-regulating the expression of telomerase associated protein and inhibiting
      the poly(ADP-ribosyl)ation of telomerase reverse transcriptase in cultured cells.
AB  - To test the role of poly(ADP-ribose) polymerase on the telomerase activity, we
      determined the telomerase activity in leukemic cells K562 treated with benzamide
      and 4-amino 1,8 naphthalimide (NAP), the inhibitors of PARP. We observed that
      both the agents inhibited telomerase activity in a dose-dependent manner. The
      doses of benzamide and NAP that inhibited telomerase activity to 50% of untreated
      control cells were 10.7 +/- 0.6 mm and 200 +/- 7 microm, respectively. Benzamide
      treatment (10 mm) inhibited telomerase activity in a time-dependent manner. We
      also tested the ability of benzamide to inhibit the telomerase activity in
      Chinese hamster V79 cells and observed similar inhibition of the telomerase
      activity. Expression of telomerase reverse transcriptase (TERT) and telomerase
      RNA component, detected by RT-PCR, remained unaltered by treatment with benzamide
      or NAP. On the contrary, the expression of telomerase associated protein
      (TEP1/TP1), as detected by RT-PCR and western blot analysis, was reduced by both
      the agents. Further, in K562 cells, immunoprecipitation with the anti-TERT IgG
      and probed anti-poly (ADP-ribose) IgG revealed that TERT was poly(ADP
      ribosyl)ated in the physiological condition of cell growth and such poly(ADP
      ribosyl)ation was inhibited by benzamide treatment. Decrease in TEP1/TP1
      expression and poly(ADP-ribosyl)ation of TERT were correlated with the inhibition
      of PARP activity by benzamide, indicating that PARP had a role in telomerase
      activity through poly(ADP-ribosyl)ation of TERT and down-regulation of TEP1/TP1.

PMID- 16098205
TI  - K4, K9 and K18 in human histone H3 are targets for biotinylation by biotinidase.
AB  - Histones are modified post-translationally, e.g. by methylation of lysine and
      arginine residues, and by phosphorylation of serine residues. These modifications
      regulate processes such as gene expression, DNA repair, and mitosis and meiosis.
      Recently, evidence has been provided that histones are also modified by covalent
      binding of the vitamin biotin. The aims of this study were to identify
      biotinylation sites in histone H3, and to investigate the crosstalk among histone
      biotinylation, methylation and phosphorylation. Synthetic peptides based on the
      sequence of human histone H3 were used as substrates for enzymatic biotinylation
      by biotinidase; biotin in peptides was probed using streptavidin peroxidase.
      These studies provided evidence that K4, K9 and K18 in histone H3 are good
      targets for biotinylation; K14 and K23 are relatively poor targets. Antibodies
      were generated to histone H3, biotinylated either at K4, K9 or K18. These
      antibodies localized to nuclei in human placental cells in immunocytochemistry
      and immunoblotting experiments, suggesting that lysines in histone H3 are
      biotinylated in vivo. Dimethylation of R2, R8 and R17 increased biotinylation of
      K4, K9 and K18, respectively, by biotinidase; phosphorylation of S10 abolished
      biotinylation of K9. These observations are consistent with crosstalk between
      biotinylation of histones and other known modifications of histones. We speculate
      that this crosstalk provides a link to known roles for biotin in gene expression
      and cell proliferation.

PMID- 16098206
TI  - Properties and significance of apoFNR as a second form of air-inactivated [4Fe
      4S].FNR of Escherichia coli.
AB  - The active form of the oxygen sensor fumarate nitrate reductase regulator (FNR)
      of Escherichia coli contains a [4Fe-4S] cluster which is converted to a [2Fe-2S]
      cluster after reaction with air, resulting in inactivation of FNR. Reaction of
      reconstituted [4Fe-4S].FNR with air resulted within 5 min in conversion to
      apoFNR. The rate was comparable to the rate known for [4Fe-4S].FNR/[2Fe-2S].FNR
      cluster conversion, suggesting that apoFNR is a product of [2Fe-2S].FNR
      decomposition and a final form of air-inactivated FNR in vitro. Formation of
      apoFNR and the redox state of the cysteinyl residues were determined in vitro by
      alkylation. FNR contains five cysteinyl residues, four of which (Cys20, Cys23,
      Cys29 and Cys122) ligate the FeS clusters. Alkylated FNR and proteolytic
      fragments thereof were analyzed by MALDI-TOF. ApoFNR formed by air inactivation
      of [4Fe-4S].FNR in vitro contained one or two disulfides. Only disulfide pairs
      Cys16/20 and Cys23/29 were formed; Cys122 was never part of a disulfide. The same
      type of disulfide was found in apoFNR obtained during isolation of FNR,
      suggesting that cysteine disulfide formation follows a fixed pattern. ApoFNR,
      including the form with two disulfides, can be reconstituted to [4Fe-4S].FNR
      after disulfide reduction. The experiments suggest that apoFNR is a major form of
      FNR under oxic conditions.

PMID- 16098207
TI  - Structural identification of ladderane and other membrane lipids of
      planctomycetes capable of anaerobic ammonium oxidation (anammox).
AB  - The membrane lipid composition of planctomycetes capable of the anaerobic
      oxidation of ammonium (anammox), i.e. Candidatus'Brocadia anammoxidans' and
      Candidatus'Kuenenia stuttgartiensis', was shown to be composed mainly of so
      called ladderane lipids. These lipids are comprised of three to five linearly
      concatenated cyclobutane moieties with cis ring junctions, which occurred as
      fatty acids, fatty alcohols, alkyl glycerol monoethers, dialkyl glycerol diethers
      and mixed glycerol ether/esters. The highly strained ladderane moieties were
      thermally unstable, which resulted in breakdown during their analysis with GC.
      This was shown by isolation of a thermal product of these ladderanes and
      subsequent analysis with two-dimensional NMR techniques. Comprehensive MS and
      relative retention time data for all the encountered ladderane membrane lipids is
      reported, allowing the identification of ladderanes in other bacterial cultures
      and in the environment. The occurrence of ladderane lipids seems to be limited to
      the specific phylogenetic clade within the Planctomycetales able to perform
      anammox. This was consistent with their proposed biochemical function, namely as
      predominant membrane lipids of the so-called anammoxosome, the specific organelle
      where anammox catabolism takes place in the cell.

PMID- 16098208
TI  - Solution structure of human proinsulin C-peptide.
AB  - The C-peptide of proinsulin is important for the biosynthesis of insulin, but has
      been considered for a long time to be biologically inert. Recent studies in
      diabetic patients have stimulated a new debate about its possible regulatory
      role, suggesting that it is a hormonally active peptide. We describe structural
      studies of the C-peptide using 2D NMR spectroscopy. In aqueous solution, the NOE
      patterns and chemical shifts indicate that the ensemble is a nonrandom structure
      and contains substructures with defined local conformations. These are more
      clearly visible in 50% H2O/50% 2,2,2-trifluoroethanol. The N-terminal region
      (residues 2-5) forms a type I beta-turn, whereas the C-terminal region (residues
      27-31) presents the most well-defined structure of the whole molecule including a
      type III'beta-turn. The C-terminal pentapeptide (EGSLQ) has been suggested to be
      responsible for chiral interactions with an as yet uncharacterized, probably a G
      protein-coupled, receptor. The three central regions of the molecule (residues 9
      12, 15-18 and 22-25) show tendencies to form beta-bends. We propose that the
      structure described here for the C-terminal pentapeptide is consistent with the
      previously postulated CA knuckle, believed to represent the active site of the C
      peptide of human proinsulin.

PMID- 16098209
TI  - Cellular virology.

PMID- 16098210
TI  - Substrate recognition of type III secretion machines--testing the RNA signal
      hypothesis.
AB  - Secretion by the type III pathway of Gram-negative microbes transports
      polypeptides into the extracellular medium or into the cytoplasm of host cells
      during infection. In pathogenic Yersinia spp., type III machines recognize 14
      different Yop protein substrates via discrete signals genetically encoded in 7-15
      codons at the 5' portion of yop genes. Although the signals necessary and
      sufficient for substrate recognition of Yop proteins have been mapped, a clear
      mechanism on how proteins are recognized by the machinery and then initiated into
      the transport pathway has not yet emerged. As synonymous substitutions, mutations
      that alter mRNA sequence but not codon specificity, affect the function of some
      secretion signals, recent work with several different microbes tested the
      hypothesis of an RNA-encoded secretion signal for polypeptides that travel the
      type III pathway. This review summarizes experimental observations and
      mechanistic models for substrate recognition in this field.

PMID- 16098211
TI  - Structural microbiology at the pathogen-host interface.
AB  - Bacterial pathogens achieve the internalization of a multitude of virulence
      factors into eukaryotic cells. Some secrete extracellular toxins which bring
      about their own entry, usually by hijacking cell surface receptors and endocytic
      pathways. Others possess specialized secretion and translocation systems to
      directly inject bacterial proteins into the host cytosol. Recent advances in the
      structural biology of these virulence factors has begun to reveal at the
      molecular level how these bacterial proteins are delivered and modulate host
      activities ranging from cytoskeletal structure to cell cycle progression.

PMID- 16098212
TI  - Global epithelial cell transcriptional responses reveal Streptococcus pyogenes
      Fas regulator activity association with bacterial aggressiveness.
AB  - The bacterial human pathogen Streptococcus pyogenes (group A streptococci, GAS)
      is able to adhere to, internalize into and cross-talk on multiple levels with its
      host cells. To gain insight into the Fas function in pathogenesis we used
      Affymetrix human genome DNA-arrays to measure temporal and global transcriptional
      responses of HEp-2 cells infected with M49 S. pyogenes wild-type bacteria and
      DeltafasX, an isogenic S. pyogenes two-component-signal-transduction system
      mutant. A modified stringent statistical analysis method identified a total of 86
      HEp-2 cell genes as differentially transcribed upon infection over the
      investigated time course. Increased expression of genes encoding proteins
      involved in GAS host cell adherence and internalization (fibronectin, integrin
      alpha5) was found as a common response. In contrast to earlier reports
      investigating other GAS serotype strains, Ras superfamily and RhoA pathways are
      exploited by M49 GAS, suggesting serotype specific interactions with the host
      cell cytoskeleton. Despite transcriptional induction, secreted IL-8 levels of
      deltafasX mutant infected cells were below those of non-infected cells,
      indicating an absence of Fas expression could be important for GAS tissue
      colonization and long-term intracellular persistence. Oppositely, activity of the
      S. pyogenes Fas-system apparently promotes high adherence and internalization
      rates, massive cytokine gene transcription and cytokine release, host cell
      apoptosis via a caspase-2 activation pathway, and cytotoxicity. Thus, the S.
      pyogenes Fas two-component signal transduction system could be involved in local
      tissue destruction and general bacterial aggressiveness towards host cells.

PMID- 16098213
TI  - Antimicrobial peptides and endotoxin inhibit cytokine and nitric oxide release
      but amplify respiratory burst response in human and murine macrophages.
AB  - Antimicrobial peptides (AMPs), in addition to their antibacterial properties, are
      also chemotactic and signalling molecules that connect the innate and adaptive
      immune responses. The role of AMP [alpha defensins, LL-37, a cathepsin G-derived
      peptide (CG117-136), protegrins (PG-1), polymyxin B (PMX) and LLP1] in modulating
      the respiratory burst response in human and murine macrophages in the presence of
      bacterial endotoxin [lipopolysaccharide (LPS) or lipooligosaccharide (LOS)] was
      investigated. AMP were found to neutralize endotoxin induction of nitric oxide
      and TNFalpha release in macrophages in a dose-dependent manner. In contrast,
      macrophages primed overnight with AMP and LOS or LPS significantly enhanced
      reactive oxygen species (ROS) release compared with cells primed with endotoxin
      or AMP alone, while no responses were seen in unprimed cells. This enhanced ROS
      release by macrophages was seen in all cell lines including those obtained from
      C3H/HeJ (TLR4-/-) mice. Similar effects were also seen when AMP and endotoxin
      were added directly with zymosan to trigger phagocytosis and the respiratory
      burst in unprimed RAW 264.7 and C3H/HeJ macrophages. Amplification of ROS release
      was also demonstrated in a cell-free system of xanthine and xanthine oxidase.
      Although AMP inhibited cytokine and nitric oxide induction by endotoxin in a TLR4
      dependent manner, AMP and endotoxin amplified ROS release in a TLR4-independent
      manner possibly by exerting a prolonged catalytic effect on the ROS generating
      enzymes such as the NADPH-oxidase complex.

PMID- 16098214
TI  - Leishmania donovani lipophosphoglycan disrupts phagosome microdomains in J774
      macrophages.
AB  - Clearance of pathogens by phagocytosis and their killing in phagolysosomes is a
      key aspect of our innate ability to fight infectious agents. Leishmania parasites
      have evolved ways to survive and replicate in macrophages by inhibiting phagosome
      maturation and avoiding the harsh environment of phagolysosomes. We describe here
      that during this process Leishmania donovani uses a novel strategy involving its
      surface lipophosphoglycan (LPG), a virulence factor impeding many host functions,
      to prevent the formation or disrupt lipid microdomains on the phagosome membrane.
      LPG acts locally on the membrane and requires its repetitive carbohydrate
      moieties to alter the organization of microdomains. Targeting and disruption of
      functional foci, where proteins involved in key aspects of phagolysosome
      biogenesis assemble, is likely to confer a survival advantage to the parasite.

PMID- 16098215
TI  - PilT is required for PI(3,4,5)P3-mediated crosstalk between Neisseria gonorrhoeae
      and epithelial cells.
AB  - The retractile type IV pilus participates in a number of fundamental bacterial
      processes, including motility, DNA transformation, fruiting body formation and
      attachment to host cells. Retraction of the N. gonorrhoeae type IV pilus requires
      a functional pilT. Retraction generates substantial force on its substrate (> 100
      pN per retraction event), and it has been speculated that epithelial cells sense
      and respond to these forces during infection. We provide evidence that piliated,
      Opa non-expressing Neisseria gonorrhoeae activates the stress-responsive PI-3
      kinase/Akt (PKB) pathway in human epithelial cells, and activation is enhanced by
      a functional pilT. PI-3 kinase inhibitors wortmannin and LY294002 reduce cell
      entry by 81% and 50%, respectively, illustrating the importance of this cascade
      in bacterial invasion. PI-3 kinase and its direct downstream effectors
      [PI(3,4,5)P3] and Akt are concentrated in the cell cortex beneath adherent
      bacteria, particularly at the periphery of the bacterial microcolonies.
      Furthermore, [PI(3,4,5)P3] is translocated to the outer leaflet of the plasma
      membrane. Finally, we show that [PI(3,4,5)P3] stimulates microcolony formation
      and upregulates pilT expression in vitro. We conclude that N. gonorrhoeae
      activation of PI-3 kinase triggers the host cell to produce a lipid second
      messenger that influences bacterial behaviour.

PMID- 16098216
TI  - Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases,
      RPTPalpha and RPTPbeta, by Helicobacter pylori m2VacA.
AB  - Helicobacter pylori vacuolating cytotoxin, VacA, induces vacuolation in mammalian
      cell lines. Sequence differences in the middle of VacA molecules define two
      families, termed m1VacA and m2VacA, which differ in cell specificity. Similar to
      m1VacA, m2VacA is activated by acid or alkali, which enhances its binding to
      cells. Immunoprecipitation experiments showed that, in AZ-521 cells, activated
      m2VacA, similar to m1VacA, binds to two receptor-like protein tyrosine
      phosphatases, RPTPalpha and RPTPbeta suggesting that activated m2VacA as well as
      m1VacA may contribute to gastrointestinal disease following H. pylori infection.
      G401 cells express RPTPalpha, not RPTPbeta, and responded to both m1VacA and
      m2VacA. HeLa cells likewise expressed RPTPalpha, not RPTPbeta, but, in contrast
      to other cell lines, responded poorly to m2VacA. m1VacA associated with RPTPalpha
      of HeLa cells to an extent similar to that in other toxin-sensitive cells,
      whereas activated m2VacA bound HeLa cell RPTPalpha less well, consistent with its
      low vacuolating activity against these cells. The molecular mass of RPTPalpha
      from HeLa cells is less than that of the protein from G401 cells, although their
      extracellular amino acid sequences are virtually identical, with only two amino
      acid differences noted. Different post-translational modifications of RPTPalpha
      in HeLa cells may be responsible for the reduced susceptibility to m2VacA.

PMID- 16098217
TI  - Mycobacterium ulcerans toxic macrolide, mycolactone modulates the host immune
      response and cellular location of M. ulcerans in vitro and in vivo.
AB  - Mycobacterium ulcerans produces an extracellular cutaneous infection (Buruli
      ulcer) characterized by immunosuppression. This is in stark contrast to all other
      pathogenic Mycobacteria species that cause intracellular, granulomatous
      infections. The unique mycobacterial pathology of M. ulcerans infection is
      attributed to a plasmid-encoded immunomodulatory macrolide toxin, mycolactone. In
      this article we explore the role of mycolactone in the virulence of M. ulcerans
      using mycolactone and genetically defined mycolactone negative mutants. In a
      guinea pig infection model wild-type (WT) M. ulcerans produces an extracellular
      infection whereas mycolactone negative mutants produce an intracellular
      inflammatory infection similar to that of Mycobacterium marinum. Although
      mycolactone negative mutants are avirulent, they persist for at least 6 weeks.
      Chemical complementation of M. ulcerans mutants with mycolactone restores WT M.
      ulcerans pathology. Mycolactone negative mutants are capable of growth within
      macrophages in vitro whereas macrophages are killed by WT M. ulcerans. The
      ability of mycolactone to caused delayed cell death via apoptosis has been
      reported. However, mycolactone also causes cell death via necrosis. In vitro
      mycolactone has antiphagocytic properties. Neither WT M. ulcerans nor mycolactone
      negative strains are strong neutrophil attractants. These results suggest that
      mycolactone is largely responsible for the unique pathology produced by M.
      ulcerans.

PMID- 16098218
TI  - Apoptosis signal-regulating kinase 1-mediated sustained p38 mitogen-activated
      protein kinase activation regulates mycoplasmal lipoprotein- and staphylococcal
      peptidoglycan-triggered Toll-like receptor 2 signalling pathways.
AB  - Toll-like receptor (TLR) 2 functions as a sensor for detecting various microbial
      components conserved in bacteria or fungi in innate immunity. TLR2 induces
      several signalling pathways linking to activation of the transcriptional factors
      NF-kappaB and AP-1 as well as induction of cell death. In human embryonic kidney
      293 cells expressed human TLR2, mycoplasmal lipoproteins (MLP) or staphylococcal
      peptidoglycans (PGN) induced sustained phosphorylation of p38 mitogen-activated
      protein kinase (MAPK), accompanied by generation of reactive oxygen species. This
      observation encouraged us to examine roles of apoptosis signal-regulating kinase
      1 (ASK1) in TLR2 signalling, because ASK1 is an upstream activator of p38 MAPK
      during exposure to oxidative stress and other stressful stimuli. A kinase
      inactive mutant of ASK1 greatly impaired the sustained phosphorylation of p38
      MAPK induced by MLP or PGN. This mutant also attenuated MLP- or PGN-induced
      transcriptional activities of NF-kappaB and AP-1 via inhibition of p38 MAPK
      activation. MLP- or PGN-induced cell death reactions, including DNA fragmentation
      and caspase-3/7 activation, were also down-regulated by the ASK1 mutant via p38
      MAPK inhibition. Furthermore, TLR2 signalling had a potential to phosphorylate
      and dephosphorylate ASK1 at Ser83 residue. Thus, MLP and PGN have capabilities to
      induce ASK1-dependent signalling pathways which regulate p38 MAPK activation
      through TLR2, leading to activation of NF-kappaB and AP-1 as well as induction of
      cell death.

PMID- 16098219
TI  - Carbohydrate composition of meningococcal lipopolysaccharide modulates the
      interaction of Neisseria meningitidis with human dendritic cells.
AB  - Meningococcal lipopolysaccharide (LPS) is of crucial importance for the
      pathogenesis of invasive infection. We show that sialylation and elongation of
      the alpha-chain effectively shields viable unencapsulated Neisseria meningitidis
      from recognition by human dendritic cells (DC). In contrast, beta- and gamma-
      chain of the LPS carbohydrate moiety play only a minor role in the interaction
      with DC. The protective function of the LPS for the bacteria can be counteracted
      in vivo by phase variation of the lgtA gene encoding LPS glycosyltransferase A.
      Capsule expression protects N. meningitidis efficiently from recognition and
      phagocytosis by DC independent of the LPS structure. Despite the significant
      impact of LPS composition on the adhesion and phagocytosis of N. meningitidis no
      differences were found in terms of cytokine levels secreted by DC for IL1-beta,
      IL-6, IL-8, TNF-alpha, IFN-gamma and GM-CSF. However, significantly lower levels
      of the regulatory mediator IL-10 were induced by encapsulated strains in
      comparison to isogenic unencapsulated derivatives. IL-10 secretion was shown to
      depend on phagocytosis because poly alpha-2,8 sialic acid did not influence IL-10
      secretion. The use of truncated LPS isoforms in vaccine preparations can
      therefore not only result in attenuation but also in more efficient targeting of
      DC.

PMID- 16098220
TI  - Effects of a mosquitocidal toxin on a mammalian epithelial cell line expressing
      its target receptor.
AB  - The spread of diseases transmitted by Anopheles and Culex mosquitoes, such as
      malaria and West Nile fever, is a growing concern for human health. Bacillus
      sphaericus binary toxin (Bin) is one of the few available bioinsecticides able to
      control populations of these mosquitoes efficiently. We previously showed that
      Bin binds to Cpm1, an alpha-glucosidase located on the apical side of Culex
      larval midgut epithelium. We analysed the effects of Bin by expressing a
      construct encoding Cpm1 in the mammalian epithelial MDCK cell line. Cpm1 is
      targeted to the apical side of polarized MDCK, where it is anchored by
      glycosylphosphatidylinositol (GPI) and displays alpha-glucosidase activity. Bin
      bound to transfected cells and induced a non-specific current presumably related
      to the opening of pores. The formation of these pores may be related to the
      location of the toxin/receptor complex in lipid raft microdomains. Finally, Bin
      promoted the time-dependent appearance of intracytoplasmic vacuoles but did not
      drive cell lysis. Thus, the dual functionality (enzyme/toxin receptor) of Cpm1 is
      fully conserved in MDCK cells and Cpm1 is an essential target protein for Bin
      cytotoxicity in Culex mosquitoes.

PMID- 16098221
TI  - The cholesterol-dependent cytolysin listeriolysin O aggregates rafts via
      oligomerization.
AB  - The pore-forming toxin listeriolysin O (LLO) is the main virulence factor of
      Listeria monocytogenes. LLO is known to act as a pseudo cytokine/chemokine, which
      induces a broad spectrum of host responses that ultimately influences the outcome
      of listeriosis. In the present study we demonstrate that LLO is a potent
      aggregator of lipid rafts. LLO was found to aggregate the raft associated
      molecules GM1, the GPI-anchored proteins CD14 and CD16 as well as the tyrosine
      kinase Lyn. Abrogation of the cytolytic activity of LLO by cholesterol
      pretreatment was found not to interfere with LLO's ability to aggregate rafts or
      trigger tyrosine phosphorylation in cells. However, a monoclonal antibody that
      blocks the oligomerization of LLO was found to inhibit rafts' aggregation as well
      as the induction of tyrosine phosphorylation. This implies that rafts aggregation
      by LLO which is independent of cytolytic activity, is due to the oligomerization
      of its membrane bound toxin monomers. Thus, LLO most likely induces signalling
      through the coaggregation of rafts' associated receptors, kinases and adaptors.

PMID- 16098222
TI  - The InhA1 metalloprotease allows spores of the B. cereus group to escape
      macrophages.
AB  - Bacteria of the Bacillus cereus group are resistant to the immune systems of
      various hosts and establish potent infections, implying that bacteria circumvent
      the bactericidal activity of host phagocytic cells. We investigated the fate of
      Bacillus spores after their internalization by macrophages. We found that these
      spores survive and escape from macrophages, and that the bacterial
      metalloprotease InhA1, the major component of the exosporium, is essential for
      efficient spore release from macrophages. InhA1 from Bacillus thuringiensis also
      enables Bacillus subtilis to escape from macrophages. Analysis of membrane
      permeability showed that the bacteria cause alterations in the macrophage
      membranes and that InhA1 is involved in these processes. Thus, InhA1 contributes
      to protect the bacteria against the host immune system. These findings provide
      further insight into the pathogenicity of B. cereus group members.

PMID- 16098223
TI  - Plant-induced cell death in the oomycete pathogen Phytophthora parasitica.
AB  - The activation of programmed cell death in the host during plant-pathogen
      interactions is an important component of the plant disease resistance mechanism.
      In this study we show that activation of programmed cell death in microorganisms
      also regulates plant-pathogen interactions. We found that a form of vacuolar cell
      death is induced in the oomycete Phytophthora parasitica--the agent that causes
      black shank disease in Nicotiana tabacum--by extracellular stimuli from resistant
      tobacco. The single-celled zoospores underwent cell death characterized by
      dynamic membrane rearrangements, cell shrinkage, formation of numerous large
      vacuoles in the cytoplasm and degradation of cytoplasmic components before plasma
      membrane disruption. Phytophthora cell death required protein synthesis but not
      caspase activation, and was associated with the production of intracellular
      reactive oxygen species. This characterization of plant-mediated cell death
      signalling in pathogens will enhance our understanding of the biological
      processes regulating plant-pathogen interactions, and improve our ability to
      control crop diseases.

PMID- 16098224
TI  - The genomic environment around the Aromatase gene: evolutionary insights.
AB  - BACKGROUND: The cytochrome P450 aromatase (CYP19), catalyses the aromatisation of
      androgens to estrogens, a key mechanism in vertebrate reproductive physiology. A
      current evolutionary hypothesis suggests that CYP19 gene arose at the origin of
      vertebrates, given that it has not been found outside this clade. The human CYP19
      gene is located in one of the proposed MHC-paralogon regions (HSA15q). At present
      it is unclear whether this genomic location is ancestral (which would suggest an
      invertebrate origin for CYP19) or derived (genomic location with no evolutionary
      meaning). The distinction between these possibilities should help to clarify the
      timing of the CYP19 emergence and which taxa should be investigated. RESULTS:
      Here we determine the "genomic environment" around CYP19 in three vertebrate
      species Homo sapiens, Tetraodon nigroviridis and Xenopus tropicalis. Paralogy
      studies and phylogenetic analysis of six gene families suggests that the CYP19
      gene region was structured through "en bloc" genomic duplication (as part of the
      MHC-paralogon formation). Four gene families have specifically duplicated in the
      vertebrate lineage. Moreover, the mapping location of the different paralogues is
      consistent with a model of "en bloc" duplication. Furthermore, we also determine
      that this region has retained the same gene content since the divergence of
      Actinopterygii and Tetrapods. A single inversion in gene order has taken place,
      probably in the mammalian lineage. Finally, we describe the first invertebrate
      CYP19 sequence, from Branchiostoma floridae. CONCLUSION: Contrary to previous
      suggestions, our data indicates an invertebrate origin for the aromatase gene,
      given the striking conservation pattern in both gene order and gene content, and
      the presence of aromatase in amphioxus. We propose that CYP19 duplicated in the
      vertebrate lineage to yield four paralogues, followed by the subsequent loss of
      all but one gene in vertebrate evolution. Finally, we suggest that agnathans and
      lophotrocozoan protostomes should be investigated for the presence of aromatase.

PMID- 16098225
TI  - NPC1L1 haplotype is associated with inter-individual variation in plasma low
      density lipoprotein response to ezetimibe.
AB  - BACKGROUND: NPC1L1 encodes a putative intestinal sterol transporter which is the
      likely target for ezetimibe, a new type of lipid-lowering medication. We
      previously reported rare non-synonymous mutations in NPC1L1 in an individual who
      had no plasma lipoprotein response to ezetimibe. We next hypothesized that common
      variants in NPC1L1 would underlie less extreme inter-individual variations in the
      plasma LDL cholesterol response to ezetimibe. RESULTS: In 101 dyslipidemic
      subjects, we found that NPC1L1 haplotype was significantly associated with inter
      individual variation in the response of plasma LDL cholesterol to treatment with
      ezetimibe for 12 weeks. Specifically, about one subject in eight lacked the
      common NPC1L1 haplotype 1735C-25342A-27677T and these subjects had a
      significantly greater reduction in plasma LDL cholesterol with ezetimibe than
      subjects with at least one copy of this haplotype (-35.9+4.0 versus -23.6+1.6
      percent reduction, P = 0.0054). This was paralleled by a similar non-significant
      trend of between-haplotype difference in reduction of total cholesterol.
      CONCLUSION: These preliminary pharmacogenetic results suggest that NPC1L1
      variation is associated with inter-individual variation in response to ezetimibe
      treatment.

PMID- 16098226
TI  - A screen for proteins that interact with PAX6: C-terminal mutations disrupt
      interaction with HOMER3, DNCL1 and TRIM11.
AB  - BACKGROUND: The PAX6 protein is a transcriptional regulator with a key role in
      ocular and neurological development. Individuals with heterozygous loss-of
      function mutations in the PAX6 gene have malformations of the eye and brain.
      Little is known about the interactions of PAX6 with other proteins, so we carried
      out a systematic screen for proteins that interact with PAX6. RESULTS: We used
      bioinformatics techniques to characterise a highly conserved peptide at the C
      terminus of the PAX6 protein. Yeast two-hybrid library screens were then carried
      out to identify brain-expressed proteins that interact with the C-terminal
      peptide and with the entire PAX6 proline-serine-threonine-rich domain. Three
      novel PAX6-interacting proteins were identified: the post-synaptic density (PSD)
      protein HOMER3, the dynein subunit DNCL1, and the tripartite motif protein
      TRIM11. Three C-terminal PAX6 mutations, previously identified in patients with
      eye malformations, all reduced or abolished the interactions. CONCLUSION: Our
      preliminary data suggest that PAX6 interacts with HOMER3, DNCL1 and TRIM11. We
      propose that the interaction of PAX6 with HOMER3 and DNCL1 is a mechanism by
      which synaptic activation could lead to changes in neuronal transcriptional
      activity, and that some of the neural anomalies in patients with PAX6 mutations
      could be explained by impaired protein-protein interactions.

PMID- 16098227
TI  - A nested-PCR with an Internal Amplification Control for the detection and
      differentiation of Bartonella henselae and B. clarridgeiae: an examination of
      cats in Trinidad.
AB  - BACKGROUND: Bartonella species are bacterial blood parasites of animals capable
      of causing disease in both animals and man. Cat-Scratch Disease (CSD) in humans
      is caused mainly by Bartonella henselae and is acquired from the cat, which
      serves as a reservoir for the bacteria. A second species, B. clarridgeiae is also
      implicated in the disease. Diagnosis of Bartonellosis by culture requires a week
      or more of incubation on enriched media containing blood, and recovery is often
      complicated by faster growing contaminating bacteria and fungi. PCR has been
      explored as an alternative to culture for both the detection and species
      identification of Bartonella, however sensitivity problems have been reported and
      false negative reactions due to blood inhibitors have not generally been
      addressed in test design. METHODS: A novel, nested-PCR was designed for the
      detection of Bartonella henselae and B. clarridgeiae based on the strategy of
      targeting species-specific size differences in the 16S-23S rDNA intergenic
      regions. An Internal Amplification Control was used for detecting PCR inhibition.
      The nested-PCR was utilized in a study on 103 blood samples from pet and stray
      cats in Trinidad. RESULTS: None of the samples were positive by primary PCR, but
      the Nested-PCR detected Bartonella in 32/103 (31%) cats where 16 were infected
      with only B. henselae, 13 with only B. clarridgeiae and 3 with both species. Of
      22 stray cats housed at an animal shelter, 13 (59%) were positive for either or
      both species, supporting the reported increased incidence of Bartonella among
      feral cats. CONCLUSION: The usefulness of a single PCR for the detection of
      Bartonella henselae and B. clarridgeiae in the blood of cats is questionable. A
      nested-PCR offers increased sensitivity over a primary PCR and should be
      evaluated with currently used methods for the routine detection and speciation of
      Bartonella henselae and B. clarridgeiae. In Trinidad, B. henselae and B.
      clarridgeiae are the predominant species in cats and infection appears highest
      with stray cats, however B. clarridgeiae may be present at levels similar to that
      of B. henselae in the pet population.

PMID- 16098228
TI  - Giant aneurysm of the atrial septum associated with premature closure of foramen
      ovale.
AB  - Premature closure or restriction of foramen ovale (PCFO) is a rare congenital
      anomaly that can lead to a wide spectrum of cardiac malformations. This spectrum
      of secondary malformations appears to depend on the gestational timing of closure
      of the foramen ovale and to the degree of restriction. Earlier in the gestation,
      closure of the foramen has been associated with severe hypoplasia of the left
      ventricle whereas later closure has been associated with right heart failure and
      rarely with the formation of an aneurysm of the atrial septum. We describe the
      case of a 1 day old infant in whom PCFO resulted in severe right heart failure in
      addition to the formation of a giant atrial septal aneurysm.

PMID- 16098229
TI  - Acute cytomegalovirus infection complicated by venous thrombosis: a case report.
AB  - BACKGROUND: CMV-induced vasculopathy and thrombosis have been reported, but they
      are rare conditions usually encountered in immunocompromised patients. However
      more and more complications of CMV infections are recognized in immunocompetent
      patients. CASE PRESENTATION: We present a case report of a previously healthy
      adult with cytomegalovirus infection that was complicated by tibiopopliteal deep
      venous thrombosis and in whom Factor V Leiden heterozygous mutation was found.
      CONCLUSION: This new case report emphasizes the involvement of cytomegalovirus in
      induction of vascular thrombosis in patients with predisposing risk factors for
      thrombosis. It is necessary to screen for CMV infection in patients with
      spontaneous thrombosis and an history of fever.

PMID- 16098230
TI  - Comparative analysis of expression of histone H2a genes in mouse.
AB  - BACKGROUND: At least 18 replication-dependent histone H2a genes are distributed
      in 3 Hist gene clusters on different chromosomes of the mouse genome. In this
      analysis we designed specific PCR primers for each histone H2a transcript and
      studied the expression levels and patterns using quantitative RT-PCR (qRT-PCR).
      In addition, we compared histone H3 K9 acetylation levels in the promoter regions
      of H2a genes by ChIP (chromatin immunoprecipitation)--quantitative PCR (qPCR)
      analysis. RESULTS: RT-PCR analysis indicated that all 20 histone H2a genes
      assessed in this study are expressed. The replication-dependent histone H2a genes
      have different expression levels but similar expression patterns. Among the 20
      histone H2a genes, the expression-level of H2afz, a replication-independent gene,
      was highest, and that of Hist1h2aa, a replication-dependent gene, was lowest.
      Among 18 replication-dependent H2a genes, the expression level of Hist3h2a was
      highest. The ChIP-qPCR analysis showed that histone H3 K9 acetylation levels in
      promoter regions of both H2afz and Hist3h2a are clearly higher than that in the
      promoter region of Hist1h2aa. The H3 K9 acetylation level in the promoter of
      Hist1h2aa is similar to that in the gamma-satellite region. CONCLUSION: These
      results strongly suggest that histone H3 K9 acetylation plays a role in the
      expression of histone genes.

PMID- 16098231
TI  - Effects of resistance training and protein supplementation on bone turnover in
      young adult women.
AB  - BACKGROUND: The strength of aging bone depends on the balance between the
      resorption and formation phases of the remodeling process. The purpose of this
      study was to examine the interaction of two factors with the potential to exert
      opposing influences on bone turnover, resistance exercise training and high
      dietary protein intake. It was hypothesized that resistance training by young,
      healthy, untrained women with protein intakes near recommended levels (0.8 g.kg(
      1).d(-1)) would promote bone formation and/or inhibit bone resorption, and that
      subsequent supplementation to provide 2.4 g protein.kg(-1).d(-1) would reverse
      these effects. METHODS: Bone formation was assessed with serum bone-specific
      alkaline phosphatase (BAP) and osteocalcin (OC), and bone resorption with urinary
      calcium and deoxypyridinoline (DPD). Biochemical, strength, anthropometric,
      dietary, and physical activity data were obtained from 24 healthy, untrained,
      eumenorrheic women (18-29 y) at baseline, after eight weeks of resistance
      training (3 d.wk(-1), approximately 1 hr.d(-1); 3 sets, 6-10 repetitions, 13
      exercises, 75-85% maximum voluntary contraction), and after 12 weeks of
      resistance training and 10 days of protein/placebo supplementation. Subjects were
      randomized (double-blind) to either a high protein (HP) or training control (TC)
      group and, during the final 10 days, consumed either enough purified whey protein
      to bring daily protein intake to 2.4 g.kg(-1).d(-1), or an equivalent dose of
      isoenergetic, carbohydrate placebo. RESULTS: Strength, lean tissue mass, and DPD
      increased significantly in both groups over time, while percent body fat and BAP
      decreased (repeated measures ANOVA, p < or = 0.05, Bonferroni correction). No
      significant changes were observed for serum OC or urinary calcium, and no
      significant group (TC, HP) x time (baseline, week 8, week 12) interactions
      emerged for any of the biochemical measures. CONCLUSION: (1) Twelve weeks of high
      intensity resistance training did not appear to enhance bone formation or inhibit
      bone resorption in young adult women, as assessed by biochemical markers of bone
      metabolism. (2) Subsequent maintenance of a high protein intake for 10 days in
      these regularly-training, calcium-replete women also showed no effects on bone
      metabolism.

PMID- 16098232
TI  - A functional polymorphism in the IL1B gene promoter, IL1B -31C>T, is not
      associated with cerebral malaria in Thailand.
AB  - BACKGROUND: IL-1beta and IL-1RA levels are higher in the serum of cerebral
      malaria patients than in patients with mild malaria. Recently, the level of IL1B
      expression was reported to be influenced by a polymorphism in the promoter of
      IL1, IL1B -31C>T. METHODS: To examine whether polymorphisms in IL1B and IL1RA
      influence the susceptibility to cerebral malaria, IL1B -31C>T, IL1B 3953C>T, and
      IL1RA variable number of tandem repeat (VNTR) were analysed in 312 Thai patients
      with malaria (109 cerebral malaria and 203 mild malaria patients). RESULTS: In
      this population, IL1B -31C>T and IL1RA VNTR were detected, while IL1B 3953C>T
      (i.e., IL1B 3953T) was not observed in the polymorphism screening for 32
      patients. Further analyses for IL1B -31C>T and IL1RA VNTR in 110 cerebral malaria
      and 206 mild malaria patients showed no significant association of these
      polymorphisms with cerebral malaria. CONCLUSION: The present results suggest that
      IL1B -31C>T and IL1RA VNTR polymorphisms do not play a crucial role in
      susceptibility or resistance to cerebral malaria.

PMID- 16098233
TI  - Identification of HLA-DRPhebeta47 as the susceptibility marker of
      hypersensitivity to beryllium in individuals lacking the berylliosis-associated
      supratypic marker HLA-DPGlubeta69.
AB  - BACKGROUND: Susceptibility to beryllium (Be)-hypersensitivity (BH) has been
      associated with HLA-DP alleles carrying a glutamate at position 69 of the HLA-DP
      beta-chain (HLA-DPGlu69) and with several HLA-DP, -DQ and -DR alleles and
      polymorphisms. However, no genetic associations have been found between BH
      affected subjects not carrying the HLA-DPGlu69 susceptibility marker. METHODS: In
      this report, we re-evaluated an already described patient populations after 7
      years of follow-up including new 29 identified BH subjects. An overall population
      36 berylliosis patients and 38 Be-sensitization without lung granulomas and 86 Be
      exposed controls was analysed to assess the role of the individual HLA-class II
      polymorphisms associated with BH-susceptibility in HLA-DPGlu69 negative subjects
      by univariate and multivariate analysis. RESULTS: As previously observed in this
      population the HLA-DPGlu69 markers was present in higher frequency in berylliosis
      patients (31 out of 36, 86%) than in Be-sensitized (21 out of 38, 55%, p = 0.008
      vs berylliosis) and 41 out of 86 (48%, p < 0.0001 vs berylliosis, p = 0.55 vs Be
      sensitized) Be-exposed controls.However, 22 subjects presenting BH did not carry
      the HLA-DPGlu69 marker. We thus evaluated the contribution of all the HLA-DR, -DP
      and -DQ polymorphisms in determining BH susceptibility in this subgroup of HLA
      Glu69 subjects. In HLA-DPGlu69-negatives a significant association with BH was
      found for the HLA-DQLeu26, for the HLA-DRB1 locus residues Ser13, Tyr26, His32,
      Asn37, Phe47 and Arg74 and for the HLA-DRB3 locus clusterized residues Arg11,
      Tyr26, Asp28, Leu38, Ser60 and Arg74. HLA-DRPhe47 (OR 2.956, p < 0.05) resulting
      independently associated with BH. Further, Be-stimulated T-cell proliferation in
      the HLA-DPGlu69-negative subjects (all carrying HLA-DRPhe47) was inhibited by the
      anti-HLA-DR antibody (range 70-92% inhibition) significantly more than by the
      anti-HLA-DP antibody (range: 6-29%; p < 0.02 compared to anti-HLA-DR) while it
      was not affected by the anti-HLA-DQ antibody. CONCLUSION: We conclude that HLA
      DPGlu69 is the primary marker of Be-hypersensitivity and HLA-DRPhe47 is
      associated with BH in Glu69-negative subjects, likely playing a role in Be
      presentation and sensitization.

PMID- 16098234
TI  - Autoimmune hepatitis in India: profile of an uncommon disease.
AB  - BACKGROUND: Autoimmune hepatitis (AIH) has been reported to show considerable
      geographical variation in frequency and clinical manifestations. It is considered
      a rare cause of liver disease in India. The present study was undertaken to
      determine the incidence, clinical, biochemical and histological profile of AIH in
      this part of the world. METHODS: Patients presenting with acute or chronic liver
      disease between January 1999 and June 2002 were evaluated prospectively. AIH was
      diagnosed using the international autoimmune hepatitis group criteria. Workup
      included clinical, biochemical, USG, viral markers, UGI endoscopy, AI markers
      (ANA, SMA, Anti-LKM, AMA, RF, p-ANCA) using indirect immunofluorescence and liver
      biopsy if possible. RESULTS: Forty-one of 2401 (1.70%) patients were diagnosed to
      have autoimmune liver disease. Out of these, 38 had autoimmune hepatitis and the
      rest 3 had primary biliary cirrhosis. The mean age of the patients of autoimmune
      hepatitis was 36.2 (15.9) years, 34 (89.4%) were females, and the duration of
      symptoms was 20.3 (20.5) months. Nineteen (50%) of them presented with chronic
      hepatitis, 13 (34.2%) as cirrhosis, 5 (13.1%) with acute hepatitis and 1 (2.6%)
      with cholestatic hepatitis. The presentations were jaundice in 21 (55.2%), pedal
      edema and hepatomegaly in 17 (44.7%), splenomegaly in 13 (34.2%), encephalopathy,
      abdominal pain in 9 (23.6%) and fever in 8 (21%). Twelve had esophageal varices
      and 3 had bled. Biochemical parameters were ALT 187 (360) U/L, AST 157 (193) U/L,
      ALP 246 (254) U/L, globulin 4.1 (1.6) g/dL, albumin 2.8 (0.9) g/dL, bilirubin 5.2
      (7.4) mg/dL, prothrombin time 17 (7) sec and ESR 47 (17) sec. The autoimmune
      markers were SMA (24), ANA (15), both SMA and ANA (4), AMA (1), rheumatoid factor
      (2), pANCA (1), and Anti-LKM in none. Thirty (79%) patients had definite AIH and
      eight (21%) had probable AI hepatitis. Associated autoimmune diseases was seen in
      15/38 (39.4%), diabetes 4, hypothyroidism 3, vitiligo 2, thrombocytopenia 2,
      rheumatoid arthritis 2, Sjogren's syndrome 1 and autoimmune polyglandular
      syndrome III in 1. Viral markers were positive in two patients, one presenting as
      acute hepatitis and HEV-IgM positive and another anti-HCV positive. CONCLUSION:
      In India, autoimmune hepatitis is uncommon and usually presents with chronic
      hepatitis or cirrhosis, acute hepatitis being less common. Age at presentation
      was earlier but clinical parameters and associated autoimmune diseases were
      similar to that reported from the west. Primary biliary cirrhosis is rare. Type
      II AIH was not observed.

PMID- 16098235
TI  - Molecular and therapeutic aspects of varicella-zoster virus infection.
AB  - Varicella-zoster virus (VZV) is a highly species-specific member of the
      Herpesviridae family. The virus exhibits multiple cell tropisms, infecting
      peripheral blood mononuclear cells and skin cells before establishing latency in
      sensory neurons. Such tropisms are essential both for primary infection, which
      manifests itself as chickenpox (varicella), and subsequent reactivation to cause
      herpes zoster (shingles). The highly cell-associated nature of the virus, coupled
      with its narrow host range, has resulted in the lack of an animal model that
      mimics its diseases in humans, thereby greatly hindering the study of events in
      VZV pathogenesis. Despite this, extensive studies both in vitro and in vivo in
      small-animal models have provided a fascinating insight into molecular events
      that govern VZV diseases. In addition, VZV has become the first human herpes
      virus for which a live attenuated vaccine has been developed.

PMID- 16098236
TI  - Rare variants of the gene encoding the potassium chloride co-transporter 3 are
      associated with bipolar disorder.
AB  - Recessive mutations of the potassium chloride co-transporter 3 gene ( SLC12A6 ,
      KCC3 ) cause severe peripheral neuropathy frequently associated with agenesis of
      the corpus callosum and psychoses (ACCPN). SLC12A6 is localized on chromosome
      15q14, a region where linkage to schizophrenia and bipolar disorder has
      previously been shown. Mutation analysis of SLC12A6 was carried out by direct
      sequencing of PCR-generated DNA fragments in two affected members of a multiplex
      family, and three non-affected individuals. A case-control study was performed to
      assess association of variants with bipolar disorder and schizophrenia in a large
      sample. Several variants including two rare single nucleotide polymorphisms (G/A,
      G/A) in the promoter and 5'-UTR, and a thymidine insertion in intron 4 were
      found. The two G variants and the insertion variant were co-inherited with
      chromosome 15-related schizophrenia in a large family that strongly supports the
      region on chromosome 15q14-15 between markers D15S144 and D15S132. Furthermore,
      they are in linkage disequilibrium with each other, and significantly associated
      with bipolar disorder in a case-control study. Our data strongly suggest that
      rare variants of SLC12A6 may represent risk factors for bipolar disorder.

PMID- 16098237
TI  - Molecular predictors of sensitivity to epidermal growth factor receptor tyrosine
      kinase inhibitor: confusion or clarity?

PMID- 16098238
TI  - 2005 highlights from: 41st Annual Meeting of the American Society of Clinical
      Oncology, Orlando, FL, May 2005.

PMID- 16098239
TI  - Bexarotene in combination with chemotherapy fails to prolong survival in patients
      with advanced non-small-cell lung cancer: results from the SPIRIT I and II
      trials.

PMID- 16098240
TI  - Paclitaxel poliglumex/carboplatin is similar to paclitaxel/carboplatin as first
      line treatment in elderly patients with advanced non-small-cell lung cancer and a
      poor performance status.

PMID- 16098241
TI  - Thoracic radiation therapy for limited-stage small-cell lung cancer: unanswered
      questions.
AB  - The role of thoracic radiation therapy (RT; TRT) is now established in the
      management of limited-stage small-cell lung cancer (SCLC). There is increasing
      evidence in the literature in favor of early concurrent chemoradiation therapy,
      and a gold standard of care for patients with a good performance status is twice
      daily TRT (45 Gy in 3 weeks) with concurrent cisplatin/etoposide. Five-year
      survival rates > 20% can be expected with this combined-modality approach.
      Although current clinical trials are exploring the efficacy of new
      chemotherapeutic strategies for the disease, essential questions related to the
      optimization of TRT remain unanswered. In particular, the optimal RT dose,
      fractionation, and treatment volume have not been defined. This review highlights
      the need for well-designed multinational trials aimed at the optimization and
      standardization of RT for limited-stage SCLC. These trials should integrate
      translational research studies to investigate the molecular basis of RT
      resistance and to develop biomarker profiles of prognosis.

PMID- 16098242
TI  - Chemoprevention strategies with cyclooxygenase-2 inhibitors for lung cancer.
AB  - Clinical lung cancer is the ultimate event resulting from a series of genetic and
      epigenetic alterations in the respiratory epithelium at risk. According to the
      "field carcinogenesis" theory, these alterations can occur throughout the entire
      lung. In individuals with a genetic predisposition combined with a sufficient
      amount of procarcinogenic environmental influences, a few of these sites may
      eventually progress to malignancies. Recent advances in the understanding of
      tumor biology have identified new therapeutic targets for lung cancer
      chemoprevention, among which is cyclooxgygenase (COX)-2. Ample preclinical data
      suggest that the COX-2/prostaglandin E2 (PGE2) signaling pathway plays a pivotal
      role in conferring the malignant phenotype. Produced primarily by the action of
      COX on the free arachidonic acid liberated from membrane phospholipids,
      overproduction of PGE2, which is predominantly generated by upregulation of COX
      2, is associated with a variety of mechanisms known to facilitate tumorigenesis.
      These mechanisms include abnormal expression of epithelial growth factors,
      epithelial and microvascular proliferation, resistance to apoptosis, and
      suppression of antitumor immunity. The lung is one of the major sites of PGE2
      production, and previous studies have shown elevated PGE2 levels in
      bronchoalveolar lavage fluid of patients with bronchogenic carcinoma. In animal
      models, inhibition of COX-2 and PGE2 synthesis suppresses lung tumorigenesis.
      These preclinical data suggesting the antineoplastic effect of COX-2 inhibitors
      provide the basis for several ongoing pilot clinical trials to determine the
      feasibility of COX-2 inhibition in chemoprevention of bronchogenic carcinoma.

PMID- 16098243
TI  - Open-label study of pemetrexed alone or in combination with cisplatin for the
      treatment of patients with peritoneal mesothelioma: outcomes of an expanded
      access program.
AB  - BACKGROUND: To date, few large studies have been reported of patients with
      peritoneal mesothelioma, and treatment of this disease has been largely
      extrapolated from the treatment of pleural disease. Hence, it was considered
      important to study and report on this specific patient population. Before the
      regulatory approval of pemetrexed, an expanded access program (EAP) provided
      access to eligible patients with malignant pleural or peritoneal mesothelioma.
      PATIENTS AND METHODS: Patients received pemetrexed 500 mg/m2 alone or in
      combination with cisplatin 75 mg/m2 once every 21 days for > or = 6 cycles. All
      patients received folic acid, vitamin B12, and steroid prophylaxis. Serious
      adverse events (SAEs) were compiled in a pharmacovigilance database, which
      included all patients in the EAP with pleural or peritoneal mesothelioma. From
      June 12, 2002 to February 18, 2004, 1056 patients with malignant mesothelioma
      were enrolled and received > or = 1 dose of treatment at 462 sites in the United
      States. Of these patients, 98 (9.3%) had peritoneal mesothelioma (57 previously
      treated, 38 chemotherapy-naive, and 3 with missing data). RESULTS: Response data
      were available for 73 patients (43 previously treated, 28 chemotherapy-naive, and
      2 not classified), indicating response rates of 23.3% for previously treated
      patients (0 complete responses [CRs], 10 partial responses [PRs], 21 cases of
      stable disease [SDs], 12 cases of progressive disease [PDs]) and 25% for
      chemotherapy-naive patients (3 CRs, 4 PRs, 12 SDs, and 9 PDs). Median survival
      was 13.1 months for previously treated patients and has not been reached for
      chemotherapy-naive patients. The most commonly reported SAEs for the total EAP
      were dehydration (7.2%), nausea (5.2%), and vomiting (4.9%). CONCLUSION:
      Pemetrexed with or without cisplatin had a favorable safety profile, and the
      disease control rate (CR + PR + SD) of 71.2% in the subset of patients with
      peritoneal mesothelioma indicated activity in this patient population.

PMID- 16098244
TI  - Induction paclitaxel/carboplatin followed by concurrent chemoradiation therapy
      for unresectable stage III non-small-cell lung cancer: a limited-access study-
      CALGB 9534.
AB  - BACKGROUND: This phase II cooperative group study of patients with unresectable
      stage III non-small-cell lung cancer was designed to treat patients with
      induction chemotherapy with paclitaxel and carboplatin (PC) followed by
      concurrent chemotherapy with the same chemotherapy plus thoracic irradiation to
      66 Gy. PATIENTS AND METHODS: All enrolled patients were scheduled to receive 2
      cycles of induction PC at conventional doses. All nonprogressing patients were
      subsequently treated with concurrent chemoradiation, including 7 weekly doses of
      PC and once-daily thoracic irradiation. The eligibility criteria allowed
      treatment of an expanded population of patients, unrestricted by previous weight
      loss. RESULTS: Despite the fact that 22% of patients had experienced > 5% weight
      loss in the preceding 6 months, 23 of the 40 eligible patients (58%) responded to
      the overall regimen. A 3-year failure-free survival rate of 15% and a 3-year
      overall survival rate of 27% were achieved. The 3-year overall survival rate is
      consistent with landmark cooperative group results for the combined modality
      treatment of a more highly selected patient population. CONCLUSION: The
      feasibility of this therapeutic approach in a cooperative group setting and
      inclusive of patients who were representative of the general population of stage
      III lung cancer patients was established.

PMID- 16098245
TI  - Wnt signaling in stem cells and non-small-cell lung cancer.
AB  - Evidence suggests that stem cells may be the source of mutant cells that cause
      cancers to develop and proliferate. Wnt signaling has been shown to promote self
      renewal in gut epithelial and hematopoietic stem cells and to trigger critical
      pathways in carcinogenesis. In this review, we highlight the progress in
      understanding how the Wnt pathway contributes to stem cell maintenance and its
      role in lung carcinogenesis. Although the function of stem cells in solid tumor
      development is unclear, the Wnt pathway's role in determining the fate and self
      renewal potential of cancer stem cells suggests a critical role in carcinogenesis
      and that developing drugs to inhibit this pathway may be of therapeutic interest.

PMID- 16098246
TI  - Adjuvant therapy: new treatment options with oxaliplatin-based chemotherapy.

PMID- 16098247
TI  - Recent data with oxaliplatin-containing regimens in the adjuvant treatment of
      colorectal cancer.

PMID- 16098248
TI  - Adjuvant irinotecan regimens in combination with infusional 5
      fluorouracil/leucovorin fail to improve outcomes in surgically resected
      colorectal cancer.

PMID- 16098249
TI  - Capecitabine versus continuous-infusion 5-fluorouracil for colorectal cancer: a
      retrospective efficacy and safety comparison.
AB  - For more than 40 years, 5-fluorouracil (5-FU) has been considered the most
      effective systemic agent for managing advanced colorectal cancer. However,
      continuous-infusion (CI) schedules of 5-FU require central venous access devices,
      which are associated with catheter complications and are an inconvenience to
      patients. The novel oral fluoropyrimidine capecitabine appears to offer
      comparable efficacy while providing a more convenient schedule that is often
      preferred by patients. Published phase II/III clinical studies of capecitabine
      based regimens for colorectal cancer were compared with key studies of CI 5-FU
      based regimens to assess safety, efficacy, quality of life, and
      pharmacoeconomics. Studies were identified via Medline searches and conference
      abstracts dating back to 1997. Qualitative analyses show that capecitabine as a
      single agent as well as in combination regimens is an effective first-line
      treatment for metastatic colorectal cancer, providing a higher response rate
      compared with standard 5-FU/leucovorin. Costs associated with capecitabine also
      appear to be lower than those associated with catheter-based therapies.
      Capecitabine offers physicians a more convenient treatment for advanced
      colorectal cancer, with manageable toxicity and antitumor activity comparable to
      that of CI therapies.

PMID- 16098250
TI  - Capecitabine/oxaliplatin, a safe and active first-line regimen for older patients
      with metastatic colorectal cancer: post hoc analysis of a large phase II study.
AB  - PURPOSE: The tumor-activated fluoropyrimidine capecitabine achieves response
      rates superior to those of bolus 5-fluorouracil/leucovorin (5-FU/LV) as first
      line treatment for metastatic colorectal cancer (CRC), with favorable safety and
      fewer hospitalizations. Capecitabine is also at least as effective as bolus 5
      FU/LV in the adjuvant setting, again with a favorable safety profile. Improved
      outcomes with capecitabine versus bolus 5-FU/LV in the adjuvant setting have been
      shown in overall trial populations and in patients aged >or= 70 years.
      Capecitabine/oxaliplatin (XelOx) is a safe and active combination for the first
      line treatment of metastatic CRC. PATIENTS AND METHODS: This post hoc analysis of
      a large phase II trial compared data from older and younger patients treated with
      first-line XelOx: oxaliplatin 130 mg/m(2) intravenously on day 1 followed by oral
      capecitabine 1,000 mg/m(2) twice daily for 14 days every 3 weeks. RESULTS: The
      median age of the overall population (N = 96) was 64 years (range, 34-79 years),
      including 52 younger patients (< 65 years of age) and 44 older patients (>or= 65
      years of age). Both age groups received a median of 8 cycles (range, 1-26 cycles)
      of XelOx. The XelOx regimen had similar high activity in both groups, with
      response rates of 58% (95% CI, 43%-71%) and 52% (95% CI, 37%-68%) in younger and
      older patients, respectively. In addition, time to disease progression and
      overall survival were similar in both groups (P > 0.5 for both outcomes). The
      XelOx regimen also had a favorable safety profile, with no clinically relevant
      differences between older and younger patients. The overall incidence of adverse
      events (including grade 3/4), dose reductions, and withdrawals because of adverse
      events were similar in both groups. CONCLUSION: In the context of an aging
      population, XelOx provides a highly effective and tolerable first-line treatment
      for patients with metastatic CRC.

PMID- 16098251
TI  - Changing patterns of bone and brain metastases in patients with colorectal
      cancer.
AB  - BACKGROUND: Therapeutic advances for patients with metastatic colorectal cancer
      (CRC) have been associated with prolonged survival. This study was undertaken to
      test the hypothesis that expanded treatment options and resultant improved
      survival for patients with metastatic CRC are associated with an increased
      incidence of metastases at uncommon sites. PATIENTS AND METHODS: Patients with
      metastatic CRC evaluated from 1993 to 2002 at the Fox Chase Cancer Center were
      identified. Medical records were abstracted to obtain the following: date of
      diagnosis/metastasis, primary tumor site, therapeutic agents received, survival,
      and site(s) of metastases. RESULTS: The records of 1020 patients were reviewed.
      Incidence of bone and brain metastases were 10.4% (95% CI, 8.6%-12.4%) and 3%
      (95% CI, 2.2%-4.5%), respectively. Bone metastases were more common with
      increased numbers of active systemic agents received: 0 (3.7%), 1 (9.4%), 2
      (10.9%), 3 (16.3%), and 4/5 (17.4%; P = 0.001; trend test). Patients receiving
      irinotecan or oxaliplatin were more likely to develop bone metastases (13.2% vs.
      8.3%, P = 0.01 for irinotecan; 16.9% vs. 9%, P = 0.003 for oxaliplatin). Patients
      with primary rectal versus primary colon cancer were more likely to develop bone
      metastases (16% vs. 8.6%; P = 0.001). Patients with lung metastases were more
      likely to have bone metastases (16.1% vs. 6.4%; P < 0.0001) or brain metastases
      (6.2% vs. 1.2%; P < 0.0001) than those without. CONCLUSION: These data
      demonstrate that the incidence of bone and brain metastases in patients with CRC
      is more common than previously reported and is associated with receipt of
      multiple systemic treatments. As survival improves for this patient population,
      clinicians should be aware of the potential for metastases at previously uncommon
      sites.

PMID- 16098252
TI  - Tumor response to neoadjuvant chemoradiation therapy for rectal adenocarcinoma is
      mediated by p53-dependent and caspase 8-dependent apoptotic pathways.
AB  - BACKGROUND: We tested the hypothesis that rectal tumors are most responsive to
      neoadjuvant therapy if they possess p53 and/or caspase 8 activity. PATIENTS AND
      METHODS: Fifty patients diagnosed with biopsy-proven rectal cancer underwent
      neoadjuvant chemoradiation therapy consisting of 5-fluorouracil (300 mg/m(2)
      daily) and radiation (4,500 cGy). Endorectal ultrasonography was performed before
      and after neoadjuvant therapy along with digital rectal examination and/or
      sigmoidoscopy for staging purposes and to evaluate response to therapy. All
      patients underwent resection with specimens submitted for gross and microscopic
      review. Pretreatment biopsy specimens were subjected to immunohistochemical
      staining for mutated p53 and caspase 8 bioactivity. RESULTS: The study population
      consisted of 32 men and 18 women. There were 17 complete responses (CRs; 34%), 17
      partial responses (PRs; 34%), and 16 cases of no response (NR; 32%). There were
      10 stage I tumors (20%), 22 stage II tumors (44%), and 18 stage III tumors (36%)
      in the cohort at the time of initial diagnosis. p53 protein staining (ie, mutated
      p53) was positive in 31 tumors (62%; CR, n = 8; PR, n = 11; NR, n = 12); caspase
      8 positivity was apparent in 30 specimens (60%; CR, n = 13; PR, n = 13; NR, n =
      4). In terms of pretreatment predictions, we scored 3 separate levels of response
      (CR, 3; PR, 2; NR, 1) and compared them with the expected responses (ie, p53
      positivity and caspase 8 negativity should yield NR, whereas all other
      combinations should yield responses). Wilcoxon 2-sample tests yielded a 1-sided P
      value of 0.007. CONCLUSION: The present study highlights a possible mechanism for
      tumor response to neoadjuvant manipulation, namely that dual mechanisms for
      apoptotic cell death are working in concert to cause tumor regression; one is p53
      transcription-dependent, and the other is p53 transcription-independent.

PMID- 16098253
TI  - Assessment of infusional 5-fluorouracil schedule and dose intensity: a Southwest
      Oncology Group and Eastern Cooperative Oncology Group study.
AB  - BACKGROUND: Building on results from Southwest Oncology Group trial 8905, this
      trial was designed to compare low-dose continuous infusion (LDCI) of 5
      fluorouracil (5-FU) versus intermittent high-dose infusion (HDI) of 5-FU in
      disseminated colorectal cancer (CRC) for evidence of survival advantage based on
      dose intensity. A companion trial was funded to assess molecular parameters
      associated with fluoropyrimidine response or resistance and toxicity from these
      treatments. PATIENTS AND METHODS: Eligibility included histologic diagnosis of
      disseminated CRC, measurable or evaluable disease, no previous therapy for
      metastatic disease, performance status of 0-2, and adequate renal, hepatic,
      cardiac, and hematologic function. Stratification factors were measurable versus
      evaluable disease, performance status of 0/1 versus 2, presence versus absence of
      adjuvant therapy, and presence versus absence of previous surgery and enrollment
      on the companion trial. Patients were randomized to receive (1) LDCI 5-FU 300
      mg/m(2) per day for 28 days every 5 weeks or (2) HDI 5-FU 2,600 mg/m(2) for 24
      hours each week. RESULTS: Between April 1995 and May 1999, 730 patients were
      accrued (LDCI arm, n = 360; HDI arm, n = 370). Of these, 708 eligible patients
      were assessable for survival and 690 for toxicity. Median survival for both
      groups was 13 months. Toxicity was mild; < 10% of patients in both arms had grade
      > 4 events. There were 8 study-related deaths (1%). Less than 10% of patients
      were enrolled in the companion trial. CONCLUSIONS: Increasing 5-FU dose intensity
      yields no survival advantage beyond that achieved with LDCI 5-FU. This study
      confirms the favorable toxicity profile of infusional 5-FU. Because no
      preferential benefit was observed for either infusion schedule, the more
      convenient weekly schedule should be considered for 5-FU-based combination
      regimens for disseminated CRC.

PMID- 16098254
TI  - Gene polymorphisms of epidermal growth factor receptor and its downstream
      effector, interleukin-8, predict oxaliplatin efficacy in patients with advanced
      colorectal cancer.
AB  - BACKGROUND: Researchers have recently reported an association between the
      epidermal growth factor receptor (EGFR) pathway and platinum-chemotherapy
      sensitivity in cancer patients. The (CA)(n) repeat polymorphism in intron 1 of
      the EGFR gene has been identified and found to alter EGFR expression in vitro as
      well as in vivo. A higher number of these CA repeats is associated with lower
      EGFR levels, whereas a low number of repeats is associated with higher EGFR
      levels. A second key polymorphism within the EGFR pathway (HER1 R497K) is a
      single nucleotide change (G-A) in codon 497 of the EGFR gene, which leads to an
      arginine-lysine substitution in the extracellular domain of subdomain IV.
      Furthermore, interleukin-8 (IL-8), recently identified as an EGFR downstream
      effector, plays a vital role in tumor angiogenesis and progression. Three other
      polymorphisms, each related to the IL-8 gene, have also been identified as
      playing a pivotal role in the EGFR pathway: T-251A in the promoter region of the
      IL-8 gene, G+2607C in exon 2 of the IL-8 receptor CXCR1 gene, and C+785T in exon
      11 of the IL-8 receptor CXCR2 gene. PATIENTS AND METHODS: In this study, we
      employed a 5'-end 33P-gATP-labeled polymerase chain reaction (PCR) protocol as
      well as the PCR-restriction fragment length polymorphism method in order to
      determine the genotypes for the previously mentioned polymorphisms in 105
      patients with metastatic colorectal cancer. Tests were conducted to establish
      whether these polymorphisms could predict clinical outcome to 5
      flourouracil/oxaliplatin chemotherapy. RESULTS: Among all patients assessed,
      those possessing < 20 EGFR CA repeats were more likely to show disease
      progression than were patients with >or= 20 CA repeats (P = 0.019; log-rank
      test). Also, patients with the CXCR1 GC genotype were found to have an increased
      relative risk of time to tumor progression that was 1.55 (95% CI, 0.8-3.0) times
      that of patients with the homozygous GG genotype (P = 0.17; log-rank test).
      CONCLUSION: Overall, our data suggest that gene polymorphisms active in the EGFR
      pathway may be associated with the sensitivity of colorectal cancer patients to
      platinum-based chemotherapy.

PMID- 16098255
TI  - Selenium protects against toxicity induced by anticancer drugs and augments
      antitumor activity: a highly selective, new, and novel approach for the treatment
      of solid tumors.
AB  - Limited therapeutic selectivity and tumor resistance are major obstacles to
      current chemotherapy. The development of new therapeutic modalities for solid
      tumor remains a challenge. The use of selenium, 5-methylselenocysteine (MSC), or
      seleno-L-methionine (SLM) as selective modulators of anticancer drugs is novel
      and has not been previously investigated. Selenium deficiency is associated with
      an increased risk of cancer and cancer death. Although low-dose selenium
      supplementation has been investigated in a large randomized prevention trial, its
      potential in chemotherapy toxicity prevention and enhancement of antitumor
      activity of anticancer drugs has not been evaluated. An ideal biomodulator of
      anticancer drugs would allow escalation of drug dose with the hope of enhancing
      antitumor activity and possibly reversing drug resistance. Results from this
      laboratory have demonstrated that MSC and SLM are highly effective modulators of
      irinotecan cure rates in de novo sensitive and resistant human tumor xenografts.
      Studies in mice have documented that the minimum effective dose of MSC when
      combined with irinotecan is 0.01 mg daily. The optimal schedule is to administer
      MSC orally for 7 days before and concurrently with irinotecan. The observed
      effects were not drug-specific, as similar results were obtained with taxanes,
      platinum agents, 5-fluorouracil, and anthracyclines; nor were they species
      specific, as selective effects were obtained in mice and rats and are currently
      being confirmed in ongoing clinical trials.

PMID- 16098256
TI  - Age-related changes of normal adult brain structure: analysed with diffusion
      tensor imaging.
AB  - BACKGROUND: It is known that the brain structure changes with normal aging. The
      objective of this study was to quantify the anisotropy and average diffusion
      coefficient (DCavg) of the brain in normal adults to demonstrate the
      microstructure changes of brain with aging. METHODS: One hundred and six normal
      adults were examined with diffusion tensor imaging (DTI). The fractional
      anisotropy (FA), 1-volume ratio (1-VR), relative anisotropy (RA) and average
      diffusion coefficient (DCavg) of different anatomic sites of brain were measured,
      correlated with age and compared among three broad age groups. RESULTS: Except in
      lentiform nucleus, the anisotropy increased and DCavg decreased with aging. Both
      anisotropy and DCavg of lentiform nucleus increased with aging. The normal
      reference values of DTI parameters of normal Chinese adult in major anatomic
      sites were acquired. CONCLUSIONS: DTI data obtained noninvasively can reflect the
      microstructural changes with aging. The normal reference values acquired can
      serve as reference standards in differentiation of brain white matter diseases.

PMID- 16098257
TI  - Strategies for managing the insufficiency of the proximal landing zone during
      endovascular thoracic aortic repair.
AB  - BACKGROUND: The insufficiency of the proximal landing zone (PLZ) is a frequent
      factor challenging the applicability and efficacy of endovascular repair (EVR)
      for thoracic aortic disorders. This study discusses two strategies for conquering
      this challenge. METHODS: Ten patients underwent EVR for thoracic aortic diseases
      during a one-year period ending June 30, 2004. Nine patients had DeBakey type III
      dissecting aortic aneurysm (DAA), and one had descending thoracic aortic aneurysm
      (DTAA). The PLZ, defined as the distance from the origin of the left subclavian
      artery (LSA) to the primary entry tear of the dissection or to the proximal
      aspect of DTAA, was less than 15 mm in all instances. EVR with intentional
      coverage of the LSA without any supportive bypass was employed in 6 patients with
      DAA, and the preliminary right-left carotid and left carotid-subclavian bypass
      combined with EVR in the DTAA and other 3 DAA cases. RESULTS: Technical success
      was achieved in all the patients. The patient with DTAA died from hemispheric
      cerebral infarction and subsequent multiple system organ failure following an
      uneventful recovery from the cervical reconstruction performed 1 week previously.
      In cases receiving the EVR with intentional coverage of the LSA, in two patients
      dizziness occurred, which noticeably resolved after intravenous administration of
      mannitol for 4 to 5 days, and a drop in blood pressure of the left arm was noted
      in all the cases, but remained clinically silent. No neurological deficits or
      limb ischaemia developed perioperatively or during the followup, ranging from 3
      to 12 months, and complete thrombosis of the thoracic aortic false lumen was
      revealed on CT at 3 months in the 9 patients with DAA. CONCLUSIONS: Both the
      intentional bypass absent coverage of the LSA and the adjunctive surgical bypass
      appear to be feasible and effective in managing the insufficiency of the PLZ
      during the endovascular thoracic aortic repair.

PMID- 16098258
TI  - Repair of left ventricular aneurysm during off-pump coronary artery bypass
      surgery.
AB  - BACKGROUND: Acute myocardial infarction can result in left ventricular aneurysm,
      which may in turn cause congestive heart failure, ventricular arrhythmia and
      thromboembolic events. This study evaluates results achieved with a modified
      linear closure of left ventricular aneurysms during off-pump coronary artery
      bypass surgery. METHODS: From January 2001 to May 2004, 75 patients were operated
      on for nonruptured, postinfarctional, left ventricular aneurysm during off-pump
      coronary artery bypass surgery. Repair was completed on the beating heart to
      minimize ischaemia and allow assessment of wall function and viability to guide
      closure. All patients presented with symptoms of angina and congestive heart
      failure or ventricular arrhythmia. The majority (75%) of the patients were in
      NYHA functional class III or IV. Preoperative ejection fraction was 26% +/- 9%.
      The mean left ventricular, end diastolic diameter was (57.5 +/- 7.1) mm. The
      ventricular preoperative and postoperative performances were compared. chi2 test
      and Student's t test were used to analyse the outcomes. A P value less than 0.05
      was considered significant. RESULTS: Hospital mortality was 1.3% (1/75). Coronary
      artery bypass was performed with an average of (3.3 +/- 1.2) grafts per patient.
      At the time of followup, all the patients had no symptoms. The mean NYHA class
      and ejection fraction increased significantly (P < 0.001). The mean left
      ventricular, end diastolic diameter decreased significantly (P < 0.001).
      CONCLUSIONS: Surgical closure of left ventricular aneurysm can be performed
      during off-pump coronary artery bypass. The operation is associated with a low
      inhospital mortality and morbidity. A postoperative improvement in the early term
      cardiac functions and symptoms and quality of life was documented, increasing our
      expectations of an increased long-term survival.

PMID- 16098259
TI  - Expression of NASG gene and its role in human nasopharyngeal homogenous tissue
      cells.
AB  - BACKGROUND: The NASG gene has been confirmed as a tumor-suppressor gene candidate
      related to nasopharyngeal carcinoma (NPC) by previous studies. We further
      investigated the expression and the role of NASG in the homogeneous tissue cells
      by microdissecting the samples of tissue from human NPC, and introduced a new way
      to study the expression of specific genes in tumor tissue. METHODS: The RNAlater
      reagent was used to preserve the samples of tissue from the nasopharynx of NPC
      patients. The samples were microdissected to harvest the homogeneous tissue cells
      and then total RNA was isolated from them. The antisense RNA (aRNA) was amplified
      from the total RNA by "in vitro transcription (IVT)". We investigated NASG
      expression in the homogeneous tumor cells of NPC (22 samples) and compared it
      with that in the pure epithelial pillar cells of normal nasopharyngeal (10
      samples) by semi-quantitative reverse transcription-polymerase chain reaction
      (sqRT-PCR). RESULTS: The high quality total RNA could be harvested from the
      microdissected homogeneous tissue cells of the nasopharynx, then sufficient aRNA
      was derived from it. NASG gene expression was identified using aRNA by sqRT-PCR
      and showed that there was significant difference between the average value of
      case groups and that of control group (t = -5.275, df = 30, P < 0.001). The NASG
      gene in the subgroups WHOII tended to express lower levels than those in the
      subgroup WHOIII although this difference was not statistically significant (t = 
      1.584, df = 20, P = 0.129 > 0.05). CONCLUSIONS: Microdissection was an effective
      method to obtain the homogeneous tissue cells of nasopharyngeal tissue (including
      the samples of NPC and non-NPC) in our study. Sufficient aRNA from amplifying
      total RNA could be used in sqRT-PCR to analyse the expression of NASG in the pure
      tissue cells. NASG should be a tumor-suppression gene candidate regarding to NPC.

PMID- 16098260
TI  - N-methyl-N-nitrosourea-induced apoptosis of photoreceptor cells in Sprague-Dawley
      rats via nuclear factor-kappaB.
AB  - BACKGROUND: Previous studies have showed that photooxidative stress can lead to
      down-modulation of nuclear factor-kappa B (NF-kappaB) activity causing apoptosis
      of cultured photoreceptor cells. This study aimed at investigating whether NF
      kappaB was involved in photoreceptor cells apoptosis induced by N-methyl-N
      nitrosourea (MNU) in rats. METHODS: A single intraperitoneal injection of 60
      mg/kg MNU was given to 50-day-old female rats. At different intervals after MNU
      treatment, the animals were sacrificed. Retinal damage was examined by a light
      microscope. The apoptotic index of the photoreceptor cells was detected by
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling
      (TUNEL). NF-kappaB was analysed by Western blot and Transcriptin Factor Assay
      Kits. RESULTS: The pyknosis of the photoreceptor nuclei and the disorientation of
      the outer segment of the photoreceptor layer was seen after MNU treatment for 24
      hours. The outer nuclear layer and photoreceptor layer were almost completely
      lost at 7 days. Photoreceptor cells apoptosis reached the peaked value at 24
      hours. In apoptotic cascade, the protein levels of NF-kappaB p65 were only
      detected after MNU treatment for 12 and 24 hours in the nucleus. Conversely, the
      amounts of IkappaBalpha were markedly increased in the cytoplasm as well as in
      the nucleus. The activity of NF-kappaB p65 in the nucleus was down-modulated in
      the end. CONCLUSIONS: MNU-induced photoreceptor cell destruction was attributed
      to the apoptotic process by down-regulating the activation of NF-kappaB p65.

PMID- 16098261
TI  - CMV-hFasL transgenic mice prevent from experimental autoimmune thyroiditis.
AB  - BACKGROUND: Previous studies showed that the role of Fas ligand (FasL) is not
      consistent in the pathogenesis of autoimmune thyroiditis. This study was designed
      to investigate the effects of FasL on the pathogenesis of experimental autoimmune
      thyroiditis (EAT) using CMV-human FasL (hFasL) transgenic mice. METHODS:
      Transgenic mice ubiquitously expressing hFasL were used as an animal model of EAT
      by injection of porcine thyroglobulin (pTg). Expression of hFasL was detected by
      RT-PCR and Western blot. The activity of hFasL transgenic thyrocytes killing
      Jurket cells was determined. CMV-hFasL transgenic mice and wild type (WT) mice
      were immunized with pTg and killed 28 days later to evaluate the lymphocytic
      infiltration of their thyroids. The number of CD4+ and CD8+ lymphocytes from the
      spleen was detected using FACS. The serum interferon-gamma (IFN-gamma)
      concentration was measured by ELISA. RESULTS: hFasL expression in the thyroid of
      CMV-hFasL transgenic mice was confirmed. After co-incubation of Jurket thymocytes
      with thyroid tissues of CMV-hFasL transgenic mice, the percentage of apoptotic
      cells in the CMV-hFasL transgenic thyroid group was significantly higher than
      that of the control WT thyroid group [(23.4 +/- 4.3)% vs (6.6 +/- 2.5)%, P <
      0.01]. On day 28 after immunization with pTg, the infiltration index of
      lymphocytes in thyroids of the CMV-hFasL transgenic mice was significantly lower
      than that of the WT mice [(1.0 +/- 0.5) vs (2.1 +/- 0.7), P < 0.001]. Moreover,
      the number of CD4+ and CD8+ lymphocytes of the spleen and serum IFN-gamma
      concentration were significantly decreased in the CMV-hFasL transgenic mice.
      CONCLUSIONS: FasL plays an important role in the pathogenesis of autoimmune
      thyroiditis. Transgenic mice ubiquitously expressing hFasL may strongly inhibit
      lymphocytic infiltration of the thyroid of EAT and ameliorate the course of this
      disease.

PMID- 16098262
TI  - Age-related decrease in expression of peroxisome proliferator-activated receptor
      alpha and its effects on development of dyslipidemia.
AB  - BACKGROUND: Ageing is associated with increased incidence of dyslipidemia. To
      investigate potential molecular mechanisms, the effects of age and fibrate
      administration on peroxisome proliferator-activated receptor alpha (PPARalpha)
      expression in livers of young and old rats were studied. METHODS: A total of 16
      young (2-month-old) and 16 old rats (24-month-old) were randomly assigned to a
      control group and fenofibrate group (fenofibrate in a total therapeutic dosage of
      0.5% in ratio to each treated rat weight in 14 days). RT-PCR was applied to
      evaluate hepatic mRNA expression of PPARalpha and its target genes. Western
      blotting was used to determine PPARalpha protein level in liver tissue. RESULTS:
      When compared with 2-month-old rats, the liver tissue from 24-month-old rats
      showed reduced expression of PPARalpha mRNA (52%, P < 0.05) and protein (109%, P
      < 0.01). Consequently, the mRNA levels of PPAR target genes, LPL, ACO, ACS and
      CPT-1 were markedly lowered by 19%, 8%, 13% and 9% respectively, and apoCIII
      increased by 24% in livers from 24-month-old rats, compared with values obtained
      from 2-month-old rats (P < 0.05). Fenofibrate therapy significantly lowered
      plasma triglyceride and total cholesterol levels in old rats, accompanied with
      improvement in hepatic expression of genes, including LPL, ACO, ACS, CPT-1 and
      apoCIII, but no change was found in PPARalpha expression in livers from either 24
      month or 2-month-old rats. CONCLUSIONS: The decrease in the hepatic PPARalpha
      expression is probably directly related to the lipid metabolic disturbances
      observed in old animals. The beneficial effects of fenofibrate administration in
      old rats suggests that fibrates may be useful for treating lipid disturbances in
      old people.

PMID- 16098263
TI  - Cellular toxic effects of combination of low dose of cisplatin and interstitial
      injection of 32P glass microspheres on mouse solid tumor S180.
AB  - BACKGROUND: Although 32P-glass microspheres (32P-GMS) have been used in internal
      radiotherapy for malignant tumors, it has been one of the key obstacles to
      improve the effect of radiotherapy. We investigated the cellular and
      hypersensitive effect of combined use of low dose of cisplatin and interstitial
      injection of 32P-GMS on mouse solid tumor S180. METHODS: The mice with solid
      tumor S180 were randomly divided into four groups (controls, cisplatin therapy,
      32P-GMS therapy and combination therapy). The specimens of the mice were
      sectioned two weeks after treatment and weighed. The death rate of tumor cells
      and the inhibition rate of tumor were calculated respectively. The cell cycle and
      apoptosis rate were evaluated with flow-cytometry. The ultrastructural changes of
      the four groups were observed by a transmission electron microscope. The data
      were analyzed by the chi-square test. RESULTS: The growth of tumor was slower in
      the combination therapy group than in the simple therapy groups by macrography.
      The inhibition rate and the death rate of tumor cells of the combination therapy
      group were significantly higher than those of the control group and the other two
      simple therapy groups (P < 0.05). More cell damages were displayed in the
      combination therapy group than in the other groups under the light and electronic
      microscope. CONCLUSION: Low-dose cisplatin combined with interstitial injection
      of 32P glass microspheres could be used as an effective hypersensitive regimen
      for the internal radiotherapy of mouse solid tumor S180.

PMID- 16098264
TI  - Preinfarction angina preserves myocardial microcirculation and function after
      revascularization.

PMID- 16098265
TI  - Mutation analysis of cathepsin C gene in a Chinese patient with pre-pubertal
      periodontitis.

PMID- 16098266
TI  - Therapeutic application of molecular adsorbents recirculating system in various
      pathogenic MODS/MOF patients.

PMID- 16098267
TI  - Hematopoietic-supportive effect of (2S, 3R)-ent-catechin on marrow-depressed
      mice.

PMID- 16098268
TI  - Modulation of breast cancer resistance protein mediated atypical multidrug
      resistance using RNA interference delivered by adenovirus.

PMID- 16098269
TI  - Cataract extraction in eyes with Fuchs' endothelial dystrophy in China.

PMID- 16098270
TI  - Metastatic tumor to the iris and ciliary body as an initial sign of lung cancer:
      a case report.

PMID- 16098271
TI  - Perfusion MR imaging and proton MR spectroscopy in a case of dysembryoplastic
      neuroepithelial tumor.

PMID- 16098272
TI  - Leishmaniasis cutis: report of two cases.

PMID- 16098273
TI  - Cosmetic psychopharmacology of anxiety: bioethical considerations.

PMID- 16098274
TI  - Risperidone for irritable aggression in posttraumatic stress disorder.

PMID- 16098275
TI  - Risperidone for posttraumatic stress disorder related to childhood abuse.

PMID- 16098276
TI  - Risperidone for chronic combat-related posttraumatic stress disorder.

PMID- 16098277
TI  - Anxiety and medical disorders.
AB  - Anxiety symptoms and disorders are associated with a range of general medical
      disorders. This association may be a physiologic consequence of the general
      medical disorder, a psychologic reaction to the experience of having a medical
      illness, a side effect of treatment, or a chance occurrence. This article briefly
      reviews the associations of panic disorder with seizure disorder, Kluver-Bucy
      syndrome, mitral valve prolapse, and respiratory disorders; of generalized
      anxiety disorder with chronic obstructive airway disease and cardiovascular and
      endocrine disorders; of social anxiety disorder with Parkinson's disease; of
      obsessive-compulsive disorder with striatal disorders; and of posttraumatic
      stress disorder with head injury and pain. Such associations provide important
      clues for understanding the neurobiology of anxiety disorders.

PMID- 16098278
TI  - Predictors of pharmacotherapy response in anxiety disorders.
AB  - Although treatment with different compounds such as tricyclic antidepressants,
      selective serotonin reuptake inhibitors, high-potency benzodiazepines, and
      monoamine oxidase inhibitors has been proven effective in anxiety disorders, 20%
      to 40% of patients are nonresponders. Given the limited efficacy, the delayed
      onset of response (it takes several weeks before a clinical effect can be seen
      for most of these drugs), and the occurrence of side effects associated with
      pharmacotherapy, predicting response in anxiety disorders would be immensely
      valuable. This review surveys the literature over the past years on predictors of
      response to pharmacotherapy in obsessive-compulsive disorder, social anxiety
      disorder, panic disorder, and posttraumatic stress disorder. Prediction of
      treatment response may be founded on demographic and clinical variables,
      neurochemical and electrophysiologic parameters, imaging studies, and genetic
      markers.

PMID- 16098279
TI  - Anticonvulsants in anxiety disorders.
AB  - Anticonvulsant drugs have shown promising results in the treatment of mood
      disorders, leading to the investigation of their potential efficacy in other
      psychiatric disorders. Numerous case reports, open-label trials, and placebo-
      controlled trials investigating the use of anticonvulsants in the treatment of
      anxiety disorders have yielded broad and varying results. Generally, these
      studies have indicated a potential role for anticonvulsants in the treatment of
      anxiety as monotherapy or augmentation therapy; however, these early findings
      must be supported by additional investigation in large-scale, placebo-controlled
      studies. This article reviews past and current research being done in this novel
      area of psychopharmacology.

PMID- 16098280
TI  - Cognitive behavioral therapy for obsessive-compulsive disorder: an update.
AB  - Cognitive-behavioral therapy (CBT) for obsessive-compulsive disorder (OCD) has
      been shown to be a highly effective treatment for children and adults. In the
      current review, we briefly describe the historical developments of the treatment,
      and recent findings related to five areas of inquiry: 1) Does intensity of CBT
      impact outcome? 2) Does CBT work better on some subtypes of OCD than others? 3)
      How do cognitive and behavioral strategies relate to outcome? 4) How well does
      CBT work for children and adolescents with OCD? and 5) Does the combination of
      CBT and medication work better than CBT alone? After a discussion of these
      questions, we mention some areas currently being examined.

PMID- 16098281
TI  - Effects of psychologic stress on fetal development and pregnancy outcome.
AB  - Data from animal studies show that maternal stress is associated with
      disturbances in pregnancy outcomes and offspring development and behavior,
      possibly as a result of permanent structural and functional changes termed "early
      life programming." There is growing interest in whether similar relationships are
      present in humans. Here we review recent significant findings from the literature
      on the impact of prenatal psychologic stressors on pregnancy outcome and
      offspring development, with a particular focus on the developing brain. Relevant
      papers were searched using PubMed, and reference lists from obtained articles
      were checked. In humans, prenatal stress is associated with pregnancy
      complications, developmental, cognitive, and behavioral disorders, and possible
      onset of psychopathology in later life. In contrast to the available research
      done in animals, virtually nothing is known about the effects of prenatal stress
      on morphologic fetal brain development, and the mechanisms underlying subsequent
      associated behavioral changes.

PMID- 16098282
TI  - Treatment of substance use disorders in schizophrenia: a unifying neurobiological
      mechanism?
AB  - Substance use disorders (SUDs) are highly prevalent and are associated with poor
      outcomes among individuals with schizophrenia. Integrating treatments for both
      disorders improves outcomes. Numerous individual pharmacologic and psychosocial
      treatments have shown effectiveness at reducing substance use in individuals with
      a primary diagnosis of schizophrenia and co-occurring substance use disorders. Of
      these treatments, medications such as certain atypical antipsychotics and
      naltrexone, and psychosocial treatments such as contingency management, seem to
      be particularly promising. The development and evaluation of psychopharmacologic
      and psychosocial treatments for SUDs in schizophrenia would benefit from a better
      understanding of the neurobiological mechanisms underlying the effectiveness of
      such treatments. Several theories have been put forth to explain the heightened
      risk for SUDs in schizophrenia. Of these, brain reward circuitry dysfunction,
      hypothesized to be etiologically important in SUDs, may be an especially salient
      target for treatments aimed at the reduction of substance use in patients with
      schizophrenia. We review current pharmacologic and psychosocial treatments for
      SUDs in schizophrenia, and theoretical mechanisms underlying the increased risk
      for SUDs in this population. We propose that effective treatments may in part
      work through the modulation of brain reward circuitry dysfunction.

PMID- 16098283
TI  - Brain maturation and its relevance to understanding criminal culpability of
      juveniles.
AB  - The purpose of this review is to summarize current understanding of the process
      of maturation in human brains during the juvenile period to young adulthood. We
      describe the methods used in such investigations, and outline the main findings
      regarding the course of brain development. There is much that we do not know
      about brain maturation, but there is congruence of evidence indicating that brain
      maturation is not complete until young adulthood (approximately age 21 years).
      Furthermore, the main index of maturation, which is rate of myelination, points
      to large variability in the rate of maturation among brain regions. Generally,
      maturation of association cortex is not complete by late adolescence, and within
      this cortex the prefrontal regions are last to mature. The review concludes by
      discussing the behavioral implications of these findings. The role of myelination
      is to focus and refine the operation of neural networks regulating behavior, and
      the frontal lobes specifically modulate and inhibit impulses, shaping behavior
      within the context of the environment in relation to planned action and long-term
      goals. Because the brain anatomy data indicate that people are not biologically
      prepared to exercise mature executive control required for full criminal intent
      until they reach adulthood, juveniles have diminished capacity in this regard and
      should not be eligible for the most severe punishment available for their crime.

PMID- 16098284
TI  - The brain, language, and schizophrenia.
AB  - Language is a defining and prominent feature in humans. This faculty is impaired
      in those with schizophrenia. Individuals with schizophrenia show numerous
      abnormalities in language function, including symptoms of disorganized speech,
      auditory hallucinations, thought disorders, and verbal memory impairments.
      Structural and functional brain imaging with neurocognitive testing shows various
      aspects of brain structure and function associated with language that also are
      abnormal in schizophrenia. This article comparatively reviews this research and
      relates it to understanding the symptoms and pathophysiologic features of
      schizophrenia. Understanding the neural basis of language and its disruption in
      schizophrenia provides a guide for diagnosis, subtyping, treatment, and future
      research.

PMID- 16098285
TI  - First- and second-generation antipsychotic medication and cognitive processing in
      schizophrenia.
AB  - Schizophrenia has been consistently characterized by deficits in the cognitive
      domains of executive function, working memory, attention, and episodic memory.
      Although some cognitive abnormalities, such as motor slowing, may be associated
      with antipsychotic medication administration, generally the cognitive deficits
      shown by patients with schizophrenia can be attributed at least in part to the
      disease process. Modulation of the dopamine neurotransmitter system, notably
      through D2 receptor blockade, has been associated with psychotic symptom
      reduction and cognitive performance improvements in patients with schizophrenia.
      Although first-generation antipsychotic medication treatment initially was
      thought not to result in cognitive improvement, recent studies comparing second
      generation antipsychotics to low doses of first-generation antipsychotic
      medication showed cognitive benefits for first-generation drugs, although perhaps
      not as great as that found after treatment with second-generation medication.
      Cognitive improvement associated with administration of antipsychotic medication
      may be a manifestation of improvement in general cortical information processing.
      Recent work has shown that specific genetic polymorphisms may interact with
      antipsychotic medication treatment to influence the degree to which cognitive
      abilities display improvement after treatment. In particular, the catechol-O
      methyltransferase val108/158met polymorphism has been shown to predict working
      memory improvement after administration of antipsychotic medication to patients
      with schizophrenia.

PMID- 16098286
TI  - Diagnosing schizophrenia circa 2005: how and why?
AB  - Since the introduction of the third edition of the Diagnostic and Statistical
      Manual of Mental Disorders, Third Edition in 1980, schizophrenia has been widely
      diagnosed with good to excellent levels of reliability. This is no small feat, as
      prior to the 1970s the reliability of this diagnosis over time and place was very
      poor. Although there have been some changes in the diagnostic algorithm for
      schizophrenia with subsequent revisions of the Diagnostic and Statistical Manual
      of Mental Disorders, there has been little change in the overall classification
      scheme. However, there has also been relatively little movement toward enhancing
      the validity of this diagnosis. Although there is broad consensus that what we
      now call schizophrenia is probably very heterogeneous with respect to underlying
      etiology and pathophysiology, attempts to identify more valid subtypes or
      dimensions have not progressed to the point that they are likely to be
      incorporated into diagnostic systems any time soon. The limited progress in
      defining more valid disease categories has increasingly important clinical
      implications as the field moves more and more to treatment by preset algorithms
      that are typically driven by diagnosis.

PMID- 16098287
TI  - Recovery in schizophrenia: reality or mere slogan.
AB  - As researchers have learned more about schizophrenia, recovery has become an
      increasingly prominent paradigm for understanding the goals of people with
      schizophrenia, and for guiding research and services for these individuals. This
      article provides a review of the recent literature on this topic, with
      consideration of both the outcome and process perspectives of recovery, and
      research that supports psychotherapeutic treatment for individuals recovering
      from schizophrenia. It concludes that schizophrenia can be overcome to varying
      degrees--some individuals may identify themselves as "fully recovered," whereas
      other individuals may be in a process of recovery for their entire lives. In the
      future, researchers should try to reconcile process and outcome perspectives of
      recovery, and advocate for recovery-oriented services for individuals with
      schizophrenia.

PMID- 16098289
TI  - Staging and classification of lymphoma.
AB  - In 2004, new cases of non-Hodgkin's lymphoma in the United States were estimated
      at 54,370, representing 4% of all cancers and resulting 4% of all cancer deaths,
      and new cases of Hodgkin's lymphoma were estimated at 7,880. The appropriate
      staging and management of lymphomas greatly depend on an accurate pathological
      diagnosis and classification. The recently established Revised European-American
      Classification of Lymphoid Neoplasms (REAL) and the subsequently adopted and
      updated World Health Organization (WHO) classification include modern
      cytogenetic, molecular, and immunologic techniques and knowledge and reach an
      international consensus on the classification of lymphomas. This classification
      scheme represents an advance in our understanding of lymphomas and serves as an
      operative guideline for studying and diagnosing lymphomas. Imaging techniques
      always have served as staging and monitoring tools for the clinical management of
      lymphomas. The understanding and adoption of the current classification system is
      important in refining the role of imaging modalities in the management of
      specific lymphoma. To help one understand the current classification, this
      current review gives a brief history of lymphoma classifications and summaries
      the recent classification schemes, including new entities, clinical staging
      methods, and clinical prognostic criteria.

PMID- 16098290
TI  - Initial staging of lymphoma with positron emission tomography and computed
      tomography.
AB  - Lymphomas represent a diverse range of diseases with manifold presentations,
      outlook, and therapeutic approaches. Key to the modern management of lymphoma is
      accurate delineation of the extent of disease. The inability of computed
      tomography (CT) to identify the involvement of nonenlarged nodes and its
      relatively poor sensitivity in the detection of extra-nodal sites of involvement
      limit the performance of noninvasive staging techniques. Functional imaging
      techniques such as Ga-67 scintigraphy have been used for many years to improve
      the evaluation of patients with lymphoma. While providing complementary
      information to CT in many clinical settings, functional imaging has never had
      sufficient accuracy or localizing ability to seriously challenge conventional
      primary staging paradigms. (18)F-Fluorodeoxyglucose positron emission tomography
      (FDG PET), however, has been demonstrated to have both higher sensitivity and
      specificity than CT in many comparative series. Now that this technology also can
      be performed at the same time as structural imaging in the form of hybrid PET/CT
      devices, clinicians are rethinking the methods used to select, plan, and monitor
      therapy of lymphoma patients. In our institution, FDG PET/CT has become the
      preferred initial staging tool for patients with lymphoma.

PMID- 16098291
TI  - Initial staging of lymphoma with octreotide and other receptor imaging agents.
AB  - Somatostatin receptor scintigraphy is useful in diagnosing tumors with increased
      expression of somatostatin receptors. The correct use of this technique reveals
      the localization of neuroendocrine primary tumors and unknown metastases in
      approximately 90% of patients. However, somatostatin receptor scintigraphy also
      can image many other human tumors expressing somatostatin receptors, including
      malignant lymphomas and thymomas. The sensitivity of somatostatin receptor
      scintigraphy to image somatostatin receptor-positive tumors is very high, but due
      to the variable expression of specific receptor subtypes, the specificity can be
      relatively low. This drawback is crucial in evaluating lymphoproliferative
      diseases, or, in general, when immune cells are involved. The sensitivity of
      somatostatin receptor scintigraphy for Hodgkin's lymphoma is 95%-100%, whereas
      for non-Hodgkin's lymphoma it is around 80%. It has been shown that the uptake of
      [(111)In-DTPA(0)]octreotide in lymphomas is lower compared to the uptake in
      neuroendocrine tumors. This is mainly attributed to the low number of receptors
      on immune cells compared to neuroendocrine cells; however, ligand-induced
      internalization and differential receptor regulation may also participate in
      determining this phenomenon. Therefore, caution should be taken when interpreting
      data from some studies. Several new ligands are currently under study to improve
      these limits and the expression of other neuropeptide receptors is being
      investigated to provide a molecular basis for in vivo multireceptor targeting of
      tumors. With the use of currently available somatostatin analogs, somatostatin
      receptor scintigraphy does not seem to have a significant impact in patients with
      lymphomas for diagnostic purposes. There are a few exceptions, however. Among
      these, the staging and restaging of extragastric lymphoma MALT-type may present
      some advantages. Conversely, somatostatin receptor scintigraphy in the imaging of
      thymic malignancies could enhance both our diagnostic and therapeutic
      capabilities. Somatostatin receptor scintigraphy is diagnostically relevant in
      differentiating malignant from benign lesions, especially in those patients with
      associated paraneoplastic syndromes, and is the main criterion to select patients
      suitable for therapy with somatostatin analogs. Recent findings emerging from in
      vitro studies on somatostatin receptor physiology in immune cells will certainly
      reopen and expand the potential applications of somatostatin analogs for in vivo
      diagnostic and therapeutic options.

PMID- 16098292
TI  - Evaluation of therapy for lymphoma.
AB  - Positron emission tomography (PET) using (18)F-fluorodeoxyglucose ((18)F-FDG) is
      the best noninvasive imaging technique for to assess response in patients
      suffering from lymphoma. Early response evaluation ("interim PET") after one, a
      few cycles, or at midtreatment can predict response, progression-free survival,
      and overall survival. We calculated from data of 7 studies an overall sensitivity
      to predict treatment failure of 79%, a specificity of 92%, a positive predictive
      value (PPV) of 90%, a negative predictive value (NPV) of 81%, and an accuracy of
      85%. Although it is not yet indicated to change patient management based on
      residual (18)F-FDG uptake on interim scan in chemotherapy-sensitive patients,
      prospective studies evaluating the role of an interim PET in patient management
      clearly are warranted. (18)F-FDG PET also has an important prognostic role in
      relapsing patients after reinduction chemotherapy before high-dose chemotherapy
      (HCT) followed by autologous stem cell transplantation (ASCT). However, all
      chemotherapy-sensitive patients remain candidates for HCT followed by ASCT, even
      if (18)F-FDG PET showed residual (18)F-FDG uptake. We calculated from data of 3
      studies an overestimated risk of relapse in 16% of all PET-positive patients.
      Some patients with residual (18)F-FDG uptake will have a good outcome after HCT
      followed by ASCT. (18)F-FDG PET is the imaging technique of choice for end-of
      treatment evaluation. However, (18)F-FDG is not specific for tumoral tissue.
      Active inflammatory lesions and infectious processes can be falsely interpreted
      as malignant residual cells. However, a negative (18)F-FDG PET cannot exclude
      minimal residual disease. Consequently, it is always indicated to correlate PET
      findings with clinical data, other imaging modalities, and/or a biopsy. We
      calculated, from data of 17 studies in end-of-treatment evaluation, a sensitivity
      of 76%, a specificity of 94%, a PPV of 82%, a NPV 92%, and an accuracy of 89%.

PMID- 16098293
TI  - Monitoring cardiac function in patients receiving doxorubicin.
AB  - Despite its well-known cardiotoxicity, doxorubicin continues to be an effective
      and widely used antineoplastic agent. Many efforts have focused on understanding
      the mechanism of doxorubicin-induced cardiotoxicity and on preventing it
      completely. Currently protective agents, eg, liposomal doxorubicin formulation,
      which results in less myocardial uptake, and the use of dexrazoxane, an
      intracellular iron chelator reducing the formation of radical complexes, have
      shown evidence of reducing incidences of cardiotoxicity at high dose of
      doxorubicin. However, they have not been able to completely eliminate
      cardiotoxicity. Therefore, it is crucial that careful monitoring to identify
      those patients who are at risk of developing unpredictable and sometimes
      irreversible cardiac dysfunction is conducted while allowing other patients who
      respond to doxorubicin-containing therapy to receive their maximal therapeutic
      dose. Serial measurement of left ventricular ejection fraction by radionuclide
      angiocardiography remains a useful and widely adopted modality in monitoring
      patients that are receiving doxorubicin. Efforts are continuing on finding a more
      sensitive and reliable predictor of eventual clinical cardiac dysfunction.

PMID- 16098294
TI  - Treatment of non-Hodgkin's lymphoma (NHL) with radiolabeled antibodies (mAbs).
AB  - Most patients with non-Hodgkin's lymphoma (NHL) achieve remission but, despite
      newer drugs, the natural history of this disease has not improved during the last
      20 years. Less than one half of patients with aggressive NHL are cured, and few
      of those with low-grade NHL are curable. Furthermore, NHL becomes progressively
      more chemoresistant while remaining responsive to external beam radiation
      therapy. Radioimmunotherapy (RIT) is a logical strategy for the treatment of NHL
      because this disease is multifocal and radiosensitive. Because of their
      remarkable effectiveness for RIT, 2 anti-CD20 monoclonal antibodies (mAbs), one
      labeled with (111)In for imaging or (90)Y for therapy and a second labeled with
      (131)I for imaging and therapy, have been approved for use in patients with NHL.
      These drugs have proven remarkably effective and safe. Evidence for the
      importance of the radionuclide is manifested by the data in the randomized
      pivotal phase III trial of (90)Y-ibritumomab that revealed response rates were
      several times greater in the (90)Y-ibritumomab arm than in the rituximab arm. A
      second drug for RIT, (131)I-tositumomab, was compared in a pivotal trial with the
      efficacy of the last chemotherapy received by each patient. Once again, response
      rates were much higher for RIT. Both (90)Y-ibritumomab and (131)I-tositumomab
      require preinfusion of several hundred milligrams of unlabeled anti-CD20 mAb to
      obtain "favorable" biodistribution, that is, targeting of NHL. Response rates for
      other mAbs and radionuclides in NHL also have been high but these drugs have not
      reached the approval stage. These drugs can be used safely by physicians who have
      suitable training and judgment. Unlike chemotherapy, RIT is not associated with
      mucositis, hair loss, or persistent nausea or vomiting. Although hematologic
      toxicity is dose limiting, hospitalization for febrile neutropenia is uncommon.
      Randomized trials of RIT in different formulations have not been conducted, but
      there is evidence to suggest that the mAb, antigen, radionuclide, chelator,
      linker, and dosing strategy may make a difference in the outcome.

PMID- 16098295
TI  - Effect of myocardial ischemia during dobutamine stress echocardiography on
      cardiac mortality in patients with heart failure secondary to ischemic
      cardiomyopathy.
AB  - This study assessed the effect of ischemia during dobutamine stress
      echocardiography (DSE) on cardiac mortality in patients with heart failure. We
      studied 528 patients (62 +/- 11 years of age, 402 men) who had heart failure and
      previous myocardial infarction or known coronary artery disease and underwent
      DSE. Ischemia was defined as new or worsening wall motion abnormalities or a
      biphasic response. End point during follow-up was cardiac death. Mean ejection
      fraction was 35 +/- 12%. Ischemia was detected in 407 patients (77%). During a
      mean follow-up of 3.2 +/- 2.4 years, cardiac death occurred in 150 patients
      (28%). Myocardial revascularization was performed within 4 months after DSE in
      117 patients (29%) who had ischemia. Annual rates of cardiac death were 4.8% in
      patients who did not have ischemia, 5.5% in those who had ischemia and underwent
      revascularization within 4 months, and 11.8% in those who had ischemia and were
      not revascularized (p <0.001 vs other groups). In a multivariate analysis model,
      independent predictors of cardiac death were diabetes (RR 2, 95% confidence
      interval 1.4 to 2.9), male gender (RR 1.7, 95% confidence interval 1.2 to 3.1),
      low-dose wall motion score index (RR 1.4, 95% confidence interval 1.2 to 2.6),
      and ischemia (RR 1.9, 95% confidence interval 1.3 to 3.2). Angina was not
      predictive of death. In patients who had ischemia, revascularization within 4
      months after DSE was associated with decreased risk of cardiac death (RR 0.43,
      95% confidence interval 0.3 to 0.8). In conclusion, myocardial ischemia that is
      detected by DSE is associated with increased risk of cardiac death among patients
      who have heart failure, after adjustment for left ventricular function. Patients
      who had ischemia and received revascularization within 4 months had a better
      survival than did patients who had ischemia and did not receive
      revascularization. Angina had no effect on prognosis. Therefore, patients who do
      not have angina should not be considered a lower-risk population if they have
      inducible ischemia.

PMID- 16098296
TI  - Impact of in-hospital acquired thrombocytopenia in patients undergoing primary
      angioplasty for acute myocardial infarction.
AB  - Thrombocytopenia that develops after percutaneous coronary intervention (PCI) may
      result in hemorrhagic complications, requirement for blood product transfusions,
      and potentially thrombotic or ischemic complications. The incidence and
      prognostic significance of thrombocytopenia, in patients with acute myocardial
      infarction (AMI) who undergo primary PCI have not been evaluated. In the CADILLAC
      trial 2,082 patients who had AMI within 12 hours of onset without shock were
      prospectively randomized to receive balloon angioplasty with or without abciximab
      versus stenting with or without abciximab. Acquired thrombocytopenia, defined as
      a nadir platelet count <100 x 10(9)/L in patients who did not have baseline
      thrombocytopenia, developed in 50 of 1,975 qualifying patients (2.5%) after
      primary PCI. By multivariate analysis, acquired thrombocytopenia developed more
      frequently in patients who had non-insulin-requiring diabetes mellitus (odds
      ratio 3.88 [OR], p = 0.0002), previous statin administration (OR 3.28, p =
      0.002), and use of abciximab (OR 2.06, p = 0.02) and less frequently in patients
      who had previous aspirin use (OR 0.26, p = 0.002), a higher baseline platelet
      count (OR 1.20, p < 0.0001), and greater body mass index (OR 0.90, p = 0.006).
      Patients who developed thrombocytopenia versus those who did not had higher in
      hospital rates of major hemorrhagic complications (10.0% vs 2.7%, p = 0.01),
      greater requirement for blood transfusions (10.0% vs 3.9%, p = 0.05), longer
      hospital stay (median 4.8 vs 3.6 days, p = 0.008), and increased costs (median
      dollar 14,466 vs dollar 11,629, p = 0.001). All-cause mortality was markedly
      increased at 30 days (8.0% vs 1.6%, p = 0.0008) and at 1 year (10.0% vs 3.9%, p =
      0.03) in patients who developed thrombocytopenia. In conclusion, thrombocytopenia
      that develops after primary PCI for AMI, although uncommon, is associated with
      increased hemorrhagic complications and decreased survival.

PMID- 16098297
TI  - Comparison of the prognostic effect of left versus right versus no bundle branch
      block on presenting electrocardiogram in acute myocardial infarction patients
      treated with primary angioplasty in the primary angioplasty in myocardial
      infarction trials.
AB  - The presence of bundle branch block (BBB) has been associated with poor outcomes
      in patients who have acute myocardial infarction. Whether this is true in the
      angioplasty era is not known. We sought to evaluate the outcome of patients with
      acute myocardial infarction and BBB who were treated with primary angioplasty. We
      evaluated 3,053 patients who underwent emergency catheterization in the PAMI
      trials. Patients who had left BBB (n = 48, 1.6%) on presenting electrocardiogram
      were compared with patients who had right BBB (n = 95, 3.1%) or no BBB (n =
      2,910, 95.3%). Patients who had BBB were older and more frequently had diabetes
      mellitus, peripheral vascular disease, and previous coronary artery bypass
      grafting. They had lower ejection fraction and more multivessel disease. There
      were no significant differences in door-to-balloon time, final Thrombolysis In
      Myocardial Infarction flow grade or stent use. In-hospital major adverse cardiac
      events (death, ischemic target vessel revascularization, and reinfarction) were
      higher in patients who had BBB due primarily to increased in-hospital death (left
      BBB 14.6%, right BBB 7.4%, no BBB 2.8%, p < 0.0001). In multivariate logistic
      regression analysis, left BBB was an independent predictor of in-hospital death
      (odds ratio 5.53, 95% confidence interval 1.89 to 16.1, p = 0.002). In
      conclusion, patients who have acute myocardial infarction and BBB have increased
      co-morbidities and higher mortality rates despite treatment with primary
      angioplasty. Despite early identification of multivessel disease with triage to
      angioplasty or coronary artery bypass grafting, if necessary, similar treatment
      times, and final Thrombolysis In Myocardial Infarction grade 3 flow, the presence
      of left BBB on admission electrocardiogram in patients who have acute myocardial
      infarction is an independent predictor of in-hospital mortality. Because 85% of
      deaths in patients who have left BBB occur within the first week, these patients
      should be recognized early and receive prompt and aggressive treatment.

PMID- 16098298
TI  - Prognostic usefulness of serum uric acid after acute myocardial infarction (the
      Japanese Acute Coronary Syndrome Study).
AB  - Serum uric acid (UA) levels reflect circulating xanthine oxidase activity and
      oxidative stress production. Hyperuricemia has been identified in patients who
      have congestive heart failure and is a marker of poor prognosis in such patients.
      We investigated the relation between serum UA levels and Killip's classification
      suggestive of the severity of heart failure and whether hyperuricemia influences
      mortality of patients who have acute myocardial infarction (AMI). Using the
      Japanese Acute Coronary Syndrome Study database, we evaluated 1,124 consecutive
      patients who were hospitalized within 48 hours of onset of symptoms of AMI from
      January to December 2002. There was a close relation between serum UA
      concentration and Killip's classification. Patients who developed short-term
      adverse events had high UA concentrations. Serum UA levels, Killip's class, age,
      and peak creatine phosphokinase level were significant predictors of long-term
      mortality. The hazard ratio for patients in the highest quartile of UA was 3.7
      compared with those in the lowest quartile for death after AMI after adjustment
      for independent factors that were related to mortality. The combination of the
      best UA cutoff (447 micromol/L) for predicting survival based on receiver
      operating characteristics analysis and Killip's class significantly predicted the
      prognosis of acute and long-term AMI-related complications. In conclusion, our
      results suggest that hyperuricemia after AMI is associated with the development
      of heart failure. Serum UA level is a suitable marker for predicting AMI-related
      future adverse events, and the combination of Killip's class and serum UA level
      after AMI is a good predictor of mortality in patients who have AMI.

PMID- 16098299
TI  - Relation of anemia at discharge to survival after acute coronary syndromes.
AB  - Two-year survival rate was assessed among 1,038 patients who had acute coronary
      syndromes that were classified by discharge hematocrit values as normal (>39%, n
      = 360, 34.7%), mildly anemic (33.1% to 39%, n = 430, 41.4%), or
      moderately/severely anemic (< or = 33%, n = 248, 23.9%). Worsening anemia was
      associated with a decreased 2-year survival rate (normal 95.8%, mild anemia
      91.2%, moderate/severe anemia 81.5%, p < 0.001). In multivariable analyses,
      adjusted hazard ratios for all-cause mortality were 1.57 (95% confidence interval
      0.82 to 2.96) for mild anemia and 2.46 (95% confidence interval 1.25 to 4.85) for
      moderate/severe anemia.

PMID- 16098300
TI  - Impact of platelet glycoprotein IIb/IIIa Inhibition on the paclitaxel-eluting
      stent in patients with stable or unstable angina pectoris or provocable
      myocardial ischemia (a TAXUS IV substudy).
AB  - Whether the benefits that glycoprotein IIb/IIIa inhibitors confer in patients who
      undergo bare metal stent implantation extend to drug-eluting stents is unknown.
      We performed a prespecified subgroup analysis of the TAXUS IV study population to
      examine the effect of procedural glycoprotein IIb/IIIa inhibition during
      paclitaxel-eluting stent implantation on periprocedural creatine kinase-MB (CK
      MB) levels. Glycoprotein (GP) IIb/IIIa inhibitors were administered to 57.7% of
      patients who had been randomized to receive the TAXUS stent and to 56.7% of those
      who had been randomized to receive the control stent. Among patients who received
      the TAXUS stent, the rate of CK-MB increases of >3 times the normal level was 2.6
      fold higher in those who received a GP IIb/IIIa inhibitor than in those who did
      not (11.4% vs 4.4%, p = 0.0015). Composite rates of major adverse cardiac events
      and target vessel failure were also higher at 1 month in the GP IIb/IIIa group.
      By multivariate analysis, use of GP IIb/IIIa inhibitors during stenting with the
      TAXUS stent was an independent predictor of CK-MB increases >3 times the normal
      level. Further studies are warranted.

PMID- 16098301
TI  - Comparison of dobutamine stress echocardiography with and without real-time
      perfusion imaging for detection of coronary artery disease.
AB  - In a pilot study of 27 patients, those who presented with chest pain underwent 2
      dobutamine stress echocardiographic studies, 1 with high mechanical index
      harmonic imaging to analyze wall motion without contrast and 1 with real-time low
      mechanical index perfusion imaging with intravenous Optison to assess myocardial
      perfusion and wall motion. All patients then underwent quantitative coronary
      angiography. Two independent reviewers demonstrated an improvement in sensitivity
      when analyzing myocardial perfusion. In the 21 patients who had significant
      coronary stenoses, 14 had abnormal myocardial perfusion detected at peak stress
      and 7 had abnormal wall motion detected by standard dobutamine stress
      echocardiography. There was decreased specificity with perfusion imaging by 1
      reviewer. The addition of real-time perfusion imaging after intravenous contrast
      during dobutamine stress echocardiography has the potential to improve detection
      of coronary artery disease.

PMID- 16098302
TI  - Outcome of patients undergoing balloon angioplasty in the two months prior to
      noncardiac surgery.
AB  - We report on the incidence of adverse cardiac events in 350 patients who
      underwent noncardiac surgery within 2 months of successful balloon angioplasty
      (BA) at our institution between 1988 and 2001. Three patients died
      perioperatively (n = 1) or had myocardial infarction (n = 2) (0.9%, 95%
      confidence interval [CI] 0.2% to 2.5%), which is a lower incidence than that
      reported for patients undergoing noncardiac surgery after stenting (3.9% to 32%).
      One patient died, and 2 had a nonfatal myocardial infarction. All 3 (1.6%, 95% CI
      0.3% to 4.6%) were among the 188 patients who underwent surgery within 2 weeks of
      BA. Repeat target vessel revascularization was performed in 10 patients (2.9%,
      95% CI 1.4% to 5.2%): in 3 (1.6%, 95% CI 0.3% to 4.6%) of 188 patients who
      underwent surgery within 2 weeks of BA and in 7 (5.1%, 95% CI 2.1% to 10.2%) of
      138 patients who underwent surgery within 3 to 7 weeks of BA. Therefore, in
      patients in whom percutaneous coronary revascularization is required before
      noncardiac surgery, BA appears to be safe, especially in patients who need to
      undergo surgery early after percutaneous coronary intervention.

PMID- 16098303
TI  - Preprocedural white blood cell count and major adverse cardiac events late after
      percutaneous coronary intervention in saphenous vein grafts.
AB  - Elevation of white blood cells (WBCs) is associated with worse outcomes in
      patients with coronary artery disease (CAD), including patients undergoing
      percutaneous coronary intervention (PCI) of native coronary arteries, but this
      relation has not been studied in patients with saphenous vein graft disease
      undergoing PCI. A total of 530 patients who underwent PCI of saphenous vein
      grafts from May 1997 to July 2002 were followed for >3 years. Major adverse
      coronary events (MACEs) were assessed as a composite of death, myocardial
      infarction, or revascularization during follow-up (mean 2.7 years). Patients with
      MACEs (n = 287) were younger and had more thrombotic and ostial lesions (p <
      0.05) than those without MACEs (n = 243). The preprocedural WBC count was also
      significantly higher in the MACE group than in the non-MACE group (8.1 x
      10(3)/mul, range 6.6 to 10.1, vs 7.0 x 10(3)/mul, range 5.6 to 8.2; p < 0.001).
      After adjusting for covariates, multiple logistic regression analysis revealed
      the preprocedural WBC count to be an independent predictor for MACEs (odds ratio
      1.2; 95% confidence interval 1.1 to 1.3, p < 0.001). Patients in the highest
      quartile of the preprocedural WBC level had a significantly increased risk of
      MACEs (lowest vs highest quartile, 41.3% vs 72.4%; odds ratio 3.7; 95% confidence
      interval 2.2 to 6.3). Thus, an elevated preprocedural WBC count is associated
      with increased risk of MACEs in patients undergoing PCI for saphenous vein graft
      lesions.

PMID- 16098304
TI  - Comparison of results of carotid stenting followed by open heart surgery versus
      combined carotid endarterectomy and open heart surgery (coronary bypass with or
      without another procedure).
AB  - We compared a novel strategy of carotid stenting (CS) followed by open heart
      surgery (OHS) to the combined carotid endarterectomy (CEA) and the OHS approach
      in patients requiring coronary and carotid revascularization. Between 1997 and
      2002, CS as a prelude to OHS was performed in 56 patients, and 111 patients
      underwent combined CEA+OHS. Adverse events included stroke, myocardial infarction
      (MI), death, and their combinations. At baseline, the CS+OHS group had more
      unstable/severe angina (52% vs 27%, p = 0.002), severe left ventricular
      dysfunction (20% vs 9%, p = 0.05), symptomatic carotid disease (46% vs 23%, p =
      0.002), and the need for repeat OHS (32% vs 9%, p = 0.0002). Severe contralateral
      carotid disease was more prevalent in the CEA+OHS group (28% vs 11%, p = 0.01).
      At 30 days, CS+OHS patients had a significantly lower incidence of stroke or MI
      (5% vs 19%, p = 0.02). A propensity score was created for each patient to account
      for baseline differences. In a final logistic regression model that included the
      propensity score, CS+OHS was associated with a trend toward reduced stroke or MI
      (odds ratio 0.26, 95% confidence interval 0.06 to 1.09, p = 0.06) and reduced
      death, stroke, or MI (odds ratio 0.40, 95% confidence interval 0.12 to 1.27, p =
      0.12). In conclusion, despite a higher baseline risk profile, patients who
      underwent CS+OHS had significantly fewer adverse events than those undergoing
      CEA+OHS. CS may be a safer carotid revascularization option for this challenging
      patient population.

PMID- 16098305
TI  - Comparison of lumens of intermediate coronary stenosis using 16-slice computed
      tomography versus intravascular ultrasound.
AB  - We aimed to quantify ambiguous coronary stenosis using the minimal lumen area
      with 16-slice computed tomography compared with intravascular ultrasound. The
      sensitivity, specificity, and accuracy for significant lesion classification was
      68%, 86%, and 78%, respectively. The correlation between intravascular ultrasound
      and CT minimal lumen area was r = 0.73 (p <0.001), and the 95% confidence
      interval for CT measurement was -72% to +56%.

PMID- 16098306
TI  - Prognostic value of a multiparametric risk score in patients undergoing
      dipyridamole stress echocardiography.
AB  - To set up a prognostic score including clinical data and stress echocardiographic
      findings, the data of 3,969 patients who underwent dipyridamole stress were
      analyzed. Age (hazard ratio [HR] 3.21), peak wall motion score index (HR 2.62),
      diabetes mellitus (HR 2.36), and male gender (HR 1.69) were independent
      predictors of mortality and were incorporated into a prognostic score allowing us
      to estimate 1-, 3-, and 5-year survival in the patient cohort. The
      multiparametric risk score, immediately available at the bedside, can be used to
      predict the survival of patients undergoing dipyridamole stress echocardiography.

PMID- 16098307
TI  - Early prognostic usefulness of C-reactive protein added to the Thrombolysis In
      Myocardial Infarction risk score in acute coronary syndromes.
AB  - The aim of the present study was to evaluate whether an elevated plasma C
      reactive protein (CRP) level provides any additional prognostic information to
      the validated Thrombolysis In Myocardial Infarction (TIMI) risk score in patients
      with acute coronary syndromes. For this purpose, 1,846 consecutive patients with
      either acute ST-segment elevation myocardial infarction (STEMI; 861 patients) or
      non-ST-segment elevation acute coronary syndrome (NSTEACS; 985 patients) were
      included. The incidence of 30-day death and 14-day composite of death, myocardial
      infarction (or repeat myocardial infarction) and recurrent ischemia was the
      prespecified primary end point in the STEMI and NSTEACS cohorts, respectively.
      The incidence of the primary end point was 9.8% and 23.6% in the STEMI and
      NSTEACS cohorts, respectively. A significantly increased risk of the primary end
      point was present with an increase in the STEMI and NSTEACS TIMI risk score
      (p(trend) < 0.001 for the 2 groups). A plasma CRP value of > or = 5 and > or = 3
      mg/L (defined by receiver-operating characteristic analysis) was associated with
      a significantly increased risk of the primary end point in the STEMI and NSTEACS
      cohorts, respectively (p < 0.001 for the 2 cohorts), and it was true throughout
      the subgroups of STEMI and NSTEACS TIMI risk scores. In conclusion, an elevated
      plasma CRP level appears to be a marker that adds prognostic information to the
      validated STEMI and NSTEACS TIMI risk score. The plasma CRP and TIMI risk score
      may be used together for enhanced risk stratification in the setting of acute
      coronary syndromes.

PMID- 16098308
TI  - Relation of leukocytosis to C-reactive protein and interleukin-6 among patients
      undergoing percutaneous coronary intervention.
AB  - An elevated white blood cell (WBC) count and elevated C-reactive protein (CRP)
      have been associated with an increased risk of adverse cardiac events. The
      relation between these 2 parameters of heightened systemic inflammation was
      characterized in patients who underwent percutaneous coronary intervention (PCI).
      Femoral arterial blood samples from a prospective registry of 100 patients who
      underwent PCI were obtained immediately before the procedure. The concentrations
      of CRP and interleukin-6 were determined by an enzyme-linked immunosorbent assay.
      Patients were stratified according to tertiles of ascending WBC counts before
      PCI. Univariate analysis compared patients in the highest WBC count tertile with
      the lower tertiles for clinical, angiographic, and procedural characteristics, as
      well as pre-PCI cytokine concentrations. Multiple logistic regression analysis
      was performed to examine the association between the elevated WBC count and
      baseline elevations in either CRP or interleukin-6, accounting for the
      simultaneous effect of confounding characteristics. Approximately 75% of patients
      had stable or unstable angina pectoris versus a marker-positive acute coronary
      syndrome. Patients in the highest WBC count tertile were more likely to be
      smokers, have received unfractionated heparin, have a marker-positive acute
      coronary syndrome, and have a CRP >3.0 mg/L. Multivariate analysis showed that
      only elevated troponin-I before PCI was independently associated with the highest
      WBC count tertile (odds ratio 10.9, 95% confidence interval 3.7 to 32.4, p <
      0.01). In patients with negative troponin I findings, CRP >3.0 mg/L was a
      powerful independent predictor of an elevated pre-PCI WBC count (odds ratio 3.78,
      95% confidence interval 1.07 to 13.3, p = 0.04). In conclusion, in patients with
      troponin I negative coronary syndromes, a pre-PCI elevation in the WBC count
      reflected cytokine-mediated inflammation.

PMID- 16098309
TI  - Relation of elevated periprocedural blood glucose to long-term survival after
      percutaneous coronary intervention.
AB  - Strict glycemic control improves outcomes in critically ill patients. We
      evaluated the hypothesis that strict glycemic control might be similarly
      beneficial after percutaneous coronary intervention. This study reports the
      correlation of periprocedural blood glucose with long-term survival in 1,746
      patients who underwent percutaneous coronary intervention from 1990 to 2003 in a
      Department of Veterans Affairs hospital.

PMID- 16098310
TI  - Modulation of high-density lipoproteins in a population in istanbul, Turkey, with
      low levels of high-density lipoproteins.
AB  - The extent to which high-density lipoprotein (HDL) cholesterol levels can be
      increased in patients with low HDL cholesterol is important because low HDL
      cholesterol levels increase the risk of coronary heart disease (CHD). During the
      past 14 years, we have assessed risk factors in Turks, a population in which
      extremely low HDL cholesterol levels (mean 36 mg/dl in men, 42 mg/dl in women)
      are a prime CHD risk factor. Although genetically determined to a significant
      extent, these low HDL cholesterol levels can be modulated by lifestyle factors,
      as in other populations. We measured the HDL cholesterol levels in men and women
      residing in Istanbul at 3 time points: 1990 to 1993, 1996 to 2000, and 2003. The
      mean HDL cholesterol levels increased from 45.3 +/- 9.5 mg/dl in 1990 to 1993 to
      49.7 +/- 12 mg/dl in 2003 (p <0.0001) in women, but were virtually unchanged in
      men (38 +/- 8 vs 39 +/- 10 mg/dl). In contrast to previous years, the HDL
      cholesterol levels in women in 2003 were markedly affected by education level and
      socioeconomic status, averaging 56 +/- 9 mg/dl in those with a university
      education and 48 +/- 12 mg/dl in those with a primary school education. Part of
      this difference could be explained by less smoking and more exercise and lower
      body mass index (average 25.6 +/- 4.9 vs 29.7 +/- 5.1 kg/m(2)) of the highly
      educated women. It is important to note the increase in the prevalence of obesity
      between the 1990 to 1993 interval and 2003 in men and women, including a
      remarkable change from 9.4% to 45.2% among women with a primary school education.
      None of these factors affected the HDL cholesterol levels of men by >2 mg/dl at
      any of the 3 points. In conclusion, because CHD risk changes by as much as 2% to
      4% per 1 mg/dl difference in HDL cholesterol level, the 8 mg/dl difference may
      reflect as much as a 20% to 30% reduction in CHD risk associated with the benefit
      of higher education in women. Why education failed to affect the HDL cholesterol
      levels in Turkish men remains unclear.

PMID- 16098311
TI  - Results of the National Cholesterol Education (NCEP) Program Evaluation ProjecT
      Utilizing Novel E-Technology (NEPTUNE) II survey and implications for treatment
      under the recent NCEP Writing Group recommendations.
AB  - The most recent national survey of compliance with the National Cholesterol
      Education Program (NCEP) Adult Treatment Panel (ATP) guidelines was completed
      before ATP III and showed significant underachievement of low-density lipoprotein
      (LDL) cholesterol goals. The NCEP Evaluation ProjecT Utilizing Novel E-Technology
      (NEPTUNE) II was a national survey conducted in 2003. Of the 4,885 patients, 67%
      achieved their LDL cholesterol treatment goal, including 89%, 76%, and 57%,
      respectively, in the 0 or 1 risk factor, > or = 2 risk factors or coronary heart
      disease (CHD), and CHD risk equivalent categories. The percentage with
      triglyceride concentrations > or = 200 mg/dl (2.25 mmol/L) in each risk category
      who achieved their LDL cholesterol and non-high-density lipoprotein cholesterol
      goals was 64%, 52%, and 27%, respectively. Patients with diabetes (55%) and other
      CHD risk equivalents (40%) were less likely to have achieved their LDL
      cholesterol targets than those with CHD (62%). Of the 1,447 patients with
      cardiovascular disease, 75% could be classified as very high risk according to
      the new July 2004 NCEP Writing Group recommendations, and 17.8% of those at very
      high risk had an LDL cholesterol level of <70 mg/dl (<1.81 mmol/L). In
      conclusion, these results suggest improved lipid management compared with
      previous surveys. The largest treatment gaps were found for features new to ATP
      III as of July 2004, including goal achievement for patients with CHD risk
      equivalents and for non-high-density lipoprotein cholesterol targets. Most of
      those (75%) with cardiovascular disease in NEPTUNE II would be considered very
      high risk and candidates for aggressive therapy to reach the new optional
      treatment goals.

PMID- 16098312
TI  - Utility of nonfluoroscopic three-dimensional electroanatomical mapping in
      accessory pathways with prior unsuccessful ablation attempts.
AB  - Three-dimensional electroanatomic mapping was performed to guide radiofrequency
      catheter ablation in 17 patients with accessory pathways (APs) who had undergone
      2.0 +/- 0.9 previous unsuccessful conventional procedures. In 14 patients,
      activation mapping was directed at the atrial insertion of the bypass during
      tachycardia (6 patients) or right ventricular pacing (7 patients) or by mapping
      atrial stimulus-delta-wave intervals. The ventricular insertion of the bypass was
      mapped and targeted for ablation in the remaining 3 patients. Successful AP
      ablation was obtained in all but 1 patient (94%) after a mean of 8 +/- 7
      radiofrequency pulses, without recurrences during a mean follow-up of 16 +/- 15
      months. On the basis of mapping results and successful ablation outcomes, the
      most likely causes of previous failed ablation attempts were anatomic or mapping
      reasons (13 patients), catheter manipulation-related problems (2 patients), and
      miscellaneous reasons (1 patient).

PMID- 16098313
TI  - Characterization of systemic hypertension in the San Francisco Chinese community.
AB  - This report examines the prevalence of hypertension, its management and control,
      and the use of antihypertensive medication, diet, and exercise in Chinese adults
      residing in the San Francisco community. Blood pressure (BP) was measured
      objectively using an automated oscillometric Dinamap recorder on 708 Chinese
      adults (295 men and 413 women; age range from 19 to 98 years, mean 59.7), and
      hypertension, defined as BP >140/90 mm Hg and/or the use of antihypertensive
      medications, was found in 489 (69%), most of them immigrants from China. Although
      202 patients (41%) received antihypertensive medications, only 28 (14%) achieved
      BP control (<140/90 mm Hg), and in examining the self-management of hypertension,
      it was found that only 45% of patients used low-sodium diets, and 49% performed
      regular exercises for > or = 30 minutes > or = 3 times weekly.

PMID- 16098314
TI  - Five-year follow-up by transesophageal echocardiographic studies in primary
      antiphospholipid syndrome.
AB  - This prospective study describes valvular abnormalities assessed by
      transesophageal echocardiography (TEE) in patients with primary antiphospholipid
      syndrome (APLS) over a 5-year follow-up. Of the 56 patients with APLS evaluated
      at baseline, 47 (84%) had repeat TEE examinations, including 3 patients who died
      before the end of the follow-up. The first TEE study showed cardiac involvement
      (thickening or vegetations and embolic sources) in 34 subjects (61%), with mitral
      valve thickening, the most common abnormality, present in 30 patients (54%).
      Embolic sources were found in 14 patients (25%; 9 severe spontaneous
      echocardiographic contrast, 5 Libman-Sacks endocarditis), associated with mitral
      valve thickening or stenosis in 10 patients. Over the 5-year follow-up, cardiac
      involvement was unchanged in 30 subjects (64%). New cardiac abnormalities were
      observed in 17 patients (36%), 15 (88%) with high immunoglobulin-G (IgG)
      anticardiolipin antibody (aCL) titers and 2 (12%) with low IgG aCL titers. In
      conclusion, this study showed that mitral valve thickening and embolic sources
      are frequently observed in patients with APLS. Anticoagulant and/or antiplatelet
      treatment was ineffective in terms of valvular lesion regression. New appearances
      of cardiac involvement are significantly related to high IgG aCL titers.

PMID- 16098315
TI  - Effectiveness of percutaneous intervention for patients with obstructive
      hypertrophic cardiomyopathy and coronary artery disease.
AB  - Seven patients with obstructive hypertrophic cardiomyopathy and single-vessel
      coronary artery disease underwent percutaneous revascularization of the coronary
      lesion in addition to alcohol septal ablation therapy for dynamic outflow tract
      obstruction. One year later, there was a significant reduction of dynamic left
      ventricular outflow tract obstruction and no clinical evidence of restenosis.

PMID- 16098316
TI  - Improving outcomes in fetuses and neonates with congenital displacement
      (Ebstein's malformation) or dysplasia of the tricuspid valve.
AB  - From 1984 to 2004, 66 patients were diagnosed with Ebstein's malformation (n =
      61) or congenital tricuspid valve (TV) dysplasia (n = 5) in utero or during the
      first month of life. Of these, 33 were diagnosed by fetal echocardiography at a
      median gestational age of 22 weeks, and 33 were diagnosed postnatally at a median
      age of 1 day (range 1 to 27). In 8 of the 33 prenatally diagnosed patients (24%),
      the pregnancies were terminated; in 9 (27%), the fetuses died in utero, and in 16
      (49%), the fetuses survived to birth. Seven prenatally diagnosed patients
      survived beyond the neonatal period (21% of 33). Of the 49 neonates, 35 (71%)
      survived to hospital discharge and beyond 1 month of age. Independent predictors
      of death by multivariable logistic regression analysis included right atrial area
      index >1, the absence of anterograde flow across the pulmonary valve, and
      diagnosis before 1997. Although outcomes in fetuses and neonates with congenital
      anomalies of the TV have improved in more recent experience, survival in patients
      at the severe end of the spectrum remains poor. To improve outcomes in this group
      of high-risk patients, novel approaches to management may be indicated.

PMID- 16098317
TI  - Risk factors for cerebrovascular events following fontan palliation in patients
      with a functional single ventricle.
AB  - The risk for cerebrovascular events (CVEs) is increased in children with
      functional single ventricles (FSVs). However, there are limited data indicating
      the prevalence of CVEs or the role of preventative therapy. To measure the
      prevalence of clinically evident CVEs in patients with FSVs, identify risk
      factors, and analyze the effect of aspirin on the risk for CVEs, a retrospective
      chart review was performed on all patients who underwent Fontan palliation at the
      University of Michigan from January 1, 1975, to June 30, 1998 (n = 402). Data
      collected included original anatomy, Fontan type, date of CVE, medications at the
      time of CVE, intraoperative placement of fenestration, and date of last follow
      up. The overall mortality rate was 12%. There were 38 CVEs (9%), of which only 11
      (3%, or 0.0036/patient-year) could not be attributed to a defined event
      (catheterization, extracorporeal membrane oxygenation, or cardiac arrest).
      Anticoagulation with aspirin was associated with a statistically significantly
      decreased risk for CVEs. Fontan type was not associated with the risk for CVEs.
      Thus, patients with FSVs are at increased risk for CVEs, although the de novo
      risk was low. Aspirin use is associated with a decreased risk for CVEs.

PMID- 16098318
TI  - Arterial switch operation for transposition of the great arteries combined with
      closure of paramembranous ventricular septal defect using the Amplatzer
      membranous ventricular septal occluder.
AB  - Ventricular septal defects (VSDs) complicate the arterial switch operation (ASO)
      in newborns with transposition of the great arteries because of prolonged cardiac
      arrest time and subsequent ventricular dysfunction. Three newborns with
      paramembranous VSDs were successfully treated using the newly designed Amplatzer
      membranous VSD occluder during the ASO. The implantation of a 4-mm asymmetric
      Amplatzer device in 2 patients and an 8-mm device in the third resulted in the
      complete occlusion of the septal defects. The cardiac arrest time for anatomic
      repair might be effectively reduced by this new approach in pediatric cardiac
      surgery.

PMID- 16098319
TI  - Major bleeding complications in a specialized anticoagulation service.
AB  - Major bleeding complications were investigated in 2,460 patients with 3,684
      patient-years of warfarin exposure from 2000 to 2003. The most common indications
      for anticoagulation were atrial fibrillation (30%), venous thromboembolic disease
      (28%), and mechanical heart valve prosthesis (15%). Eleven patients had 12
      nonfatal major bleeding complications, with no fatal bleeds during the study. The
      incidence of major bleeding complications was 0.12%/year; there were 0.32
      bleeds/100 patient-years of coverage. Of the 12 bleeding events, 5 (42%) were
      intracranial hemorrhages. The average hospitalization cost per patient was dollar
      15,988, and the average length of hospitalization was 6.0 days.

PMID- 16098320
TI  - Characteristics and outcomes of fetuses with pericardial effusions.
AB  - Little is known about the characteristics and outcomes of fetuses with
      pericardial effusions (PEs); therefore, this study sought to identify factors
      associated with fetal PEs and the natural histories and outcomes of fetuses with
      PEs. Large PEs are associated with a greater likelihood of structural heart
      disease, impaired cardiac function, and chromosomal abnormalities, and PEs with
      hydrops or extracardiac malformations are associated with death. Most fetal PEs
      resolve, and fetuses with isolated PEs have a very good prognosis.

PMID- 16098321
TI  - Relation of right ventricular free wall mechanical delay to right ventricular
      dysfunction as determined by tissue Doppler imaging.
AB  - Several well-established echocardiographic parameters used in the assessment of
      right ventricular (RV) performance, as well as tissue Doppler imaging (TDI) to
      investigate RV free wall mechanical events, were prospectively obtained from a
      heterogenous group of 20 patients with varying degrees of pulmonary hypertension
      (mean age 51 +/- 13 years; World Health Organization class average 2.8, mean
      pulmonary systolic pressure 78 +/- 24 mm Hg) and compared with similar data
      retrospectively obtained from 20 healthy volunteers (mean age 45 +/- 15 years).
      Patients with varying degrees of pulmonary hypertension had worse RV performance
      parameters than healthy volunteers (RV fractional area change 37 +/- 13% vs 52 +/
      5%, p < 0.0001; RV myocardial performance index 0.76 +/- 0.31 vs 0.29 +/- 0.11,
      p < 0.0001; and eccentricity index 1.41 +/- 0.57 vs 0.98 +/- 0.06, p < 0.005).
      Similarly, in these patients with abnormal RV performance, TDI showed
      statistically significant smaller peak longitudinal RV free wall strain (-21.5 +/
      9.0% vs -28.0 +/- 4.1%, p < 0.01) and significantly delayed time to peak strain
      (459 +/- 76 vs 388 +/- 29 ms, p < 0.0005) values than in healthy volunteers; a
      very strong correlation between RV mechanical delay and RV fractional area change
      (r = -0.89) was noted.

PMID- 16098323
TI  - Outcome of left ventricular hypertrabeculation/noncompaction in children.

PMID- 16098324
TI  - Can the time of taking aspirin influence the frequency of cardiovascular events?

PMID- 16098325
TI  - Pre-hospital fluid therapy in the critically injured patient--a clinical update.
AB  - Venous access and fluid therapy should still be considered to be essential
      elements of pre-hospital advanced life support (ALS) in the critically injured
      patient. Initiation of fluid therapy should be based on a clinical assessment,
      most importantly the presence, or otherwise, of a radial pulse. The goal in
      penetrating injury is to avoid hypovolaemic cardiac arrest during transport, but
      at the same time not to delay transport, or increase systolic blood pressure. The
      goal in blunt injury is to secure safe perfusion of the injured brain through an
      adequate cerebral perfusion pressure, which generally requires a systolic blood
      pressure well above 100 mmHg. Patients without severe brain injury tolerate lower
      blood pressures (hypotensive resuscitation). Importantly, using systolic blood
      pressure targets to titrate therapy is not as easy as it seems. Automated
      (oscillometric) blood pressure measurement devices frequently give erroneously
      high values. The concept of hypotensive resuscitation has not been validated in
      the few studies done in humans. Hence, the suggested targeted systolic blood
      pressures should only provide a mental framework for the decision-making. The
      ideal pre-hospital fluid regimen may be a combination of an initial hypertonic
      solution given as a 10-20 minutes infusion, followed by crystalloids and, in some
      cases, artificial colloids. This review is intended to help the clinician to
      balance the pros and cons of fluid therapy in the individual patient.

PMID- 16098326
TI  - New trends in the management of colonic trauma.
AB  - BACKGROUND: The management of colon trauma seems to have swung from the
      "diversion dogma" to a more liberal use of primary repair. However, there are
      still debatable issues, regarding the management of destructive injuries of the
      left colon. METHODS: A review of the current literature on the management of
      colon trauma was performed using PubMed, with secondary references obtained from
      key articles. CONCLUSION: There is strong evidence from prospective randomised
      trials that the vast majority of colonic injuries can be safely managed by
      primary repair. It seems, however, that there is a limited role for colostomy,
      particularly in high-risk patients with destructive injuries of the left colon.
      The final decision should be based on available scientific evidence in
      combination with personal experience and clinical judgement on the given patient.

PMID- 16098327
TI  - Injury-related deaths among Finnish adolescents in 1971-2002.
AB  - The purpose of our study was to examine the nationwide trends in the age- and sex
      specific incidence rates of fatal injuries among 10-19-year-old adolescents in
      Finland, a country with a well-defined white population of 5.2 million. A
      population-based study was based on Official Cause-of-Death Statistics of
      Finland. We included adolescents aged 10-19 years who died because of an injury
      in 1971-2002. During the study period, the incidence of injury-related deaths
      declined considerably, from 43.0 (per 100,000 persons) (95% confidence interval
      (CI): 38.5, 47.5) in 1971 to 19.9 (95% CI: 16.5, 23.4) in 2002 (p<0.001). The
      decrease was seen in both genders. The decline in injury deaths was mainly due to
      decrease of deaths in traffic accidents. A sharp peak in boys' suicides was found
      during economic depression. To sum up, the incidence of adolescent injury deaths
      declined considerably in Finland between 1971 and 2002. The reasons for this
      positive development are probably multifactorial, including improvements in
      traffic safety and emergency services. The trend in intentional deaths showed no
      change during the 32-year study period and therefore prevention of adolescent
      violence and suicides should also receive attention.

PMID- 16098328
TI  - Blunt cardiac injury associated with cardiac valve insufficiency: trauma links to
      chronic disease?
AB  - CONTEXT: Cardiac injury has been well recognised as a complication of blunt chest
      trauma. Its clinical spectrum ranges from blunt cardiac injury (BCI) to complete
      rupture of cardiac tissues, with cardiac valvular injury often being overlooked.
      OBJECTIVE: To determine whether hospitalised BCI is associated with increased
      risk of cardiac valve insufficiency in a large multi-state hospitalised
      population. METHODS: Cases with BCI and cardiac valve insufficiency were
      identified based on discharge diagnoses in 1997 statewide hospital discharge data
      from 19 states. Four valvular outcomes were studied: (1) mitral valve
      insufficiency, incompetence, regurgitation (MVIIR); (2) aortic valve
      insufficiency, incompetence, regurgitation, stenosis (AVIIRS); (3) tricuspid
      valve insufficiency, incompetence, regurgitation, stenosis (TVIIRS); and (4)
      pulmonary valve insufficiency, incompetence, regurgitation, stenosis (PVIIRS).
      RESULTS: Among 1,051,081 injury discharges, 2709 (0.26%) people had BCI; 13,087
      (1.25%) had MVIIR; 9811 (0.93%) had AVIIRS; 1338 (0.13%) had TVIIRS; 178 (0.02%)
      had PVIIRS. Independent of potential confounding factors, discharge for BCI was
      associated with a 12-fold increased risk for TVIIRS and a 3.4-fold increased risk
      for AVIIRS. CONCLUSION: Cardiac valve insufficiency has been well recognised as
      an important risk factor for congestive heart failure. With the findings that BCI
      is associated with an increased risk of specific valvular disorders, it is
      possible that trauma may play an important and heretofore largely unrecognised
      role in a portion of the burden of cardiovascular morbidity and mortality.

PMID- 16098329
TI  - Perforating small bowel injuries in children: influence of time to operation on
      outcome.
AB  - The purpose of this study was to determine whether delay in the diagnosis of
      small bowel injury (SBI) affected the outcome of paediatric patients who required
      surgical interventions in the treatment of small bowel injuries. A retrospective
      chart review was performed on children with traumatic SBI requiring surgical
      management between January 2000 and December 2002. Diagnostic interval was
      defined as the time from presentation to operative treatment and delay was an
      interval of greater than 8 h. Thirteen patients were admitted for operative
      treatment of SBI. Nine cases were the result of motor vehicle trauma. The mean
      diagnostic interval for all patients was 9.1 h+/-7.4 h (range 0.6 h-22.5 h). Six
      patients had a diagnostic delay with a mean diagnostic interval of 15.5 h+/-5.5
      h. There was no statistically significant difference found between the prompt and
      delayed diagnosis groups in terms of complications or length of hospital stay.
      Our finding of no difference between the prompt and delayed diagnosis groups and
      a diagnostic delay no longer than 22.5 h may suggest that our local methods of
      diagnosis and treatment assist in the prevention of unnecessary complications and
      death.

PMID- 16098331
TI  - Penetrating arrow injuries in Western India.
AB  - BACKGROUND: Though penetrating arrow injuries are a rarity in the West, they are
      still seen frequently among the tribal population of India. This study was
      performed with the aim of documenting the clinical profile of injuries caused by
      arrows, the varied modes of clinical presentation and their management at a
      university hospital. METHODS: A retrospective study of indoor records of 70
      patients admitted over a period of 5 years at the Sir Sayajirao General Hospital
      (SSGH), Baroda, Gujarat, India, was carried out. RESULTS: A majority of patients
      were males (n=67), the median age being 36 years. The median delay in
      presentation to the hospital was 11 h. Median TRISS score was 98.2%. There were
      three mortalities. Major wound infection (n=1), intestinal fistula (n=1) and
      multiple organ dysfunction syndrome (n=2) were the noteworthy complications.
      CONCLUSION: Arrow injury and its astute management is still relevant in this
      century. Delay in treatment and a poor TRISS score adversely affects survival.
      Optimal exploration, adequate mobilisation, minimising haemorrhage and repair are
      the building blocks of successful treatment.

PMID- 16098332
TI  - An evaluation of compliance with practice guidelines on interhospital trauma
      transfer.
AB  - STUDY OBJECTIVES: To prospectively evaluate compliance with current interhospital
      trauma transfer guidelines in South West Sydney, before and after an
      implementation programme was instituted. METHODS: A scoring system was developed
      to assess compliance with the 11 main components of the guideline. Baseline
      compliance was measured during an initial 3-month period (pre), followed by an
      implementation programme to alert staff at referring hospitals to the presence of
      the guidelines. Following this, compliance was again measured over 3 months
      (post). RESULTS: Twenty-two patients were transferred during the pre
      implementation phase and 35 patients during the post-phase. Overall compliance
      with the guidelines increased from 62 to 67%. Mean pre-hospital compliance rose
      from 75 to 95%, and referring hospital compliance rose from 59 to 63%. While
      there was an improvement in compliance with the use of the dedicated trauma
      hotline (86-97%), the use of a transfer checklist (41-53%), and appropriateness
      of transfer (95-100%), none of these reached statistical significance.
      CONCLUSION: Practice guidelines have been developed to optimise the process of
      interhospital trauma transfers. An implementation programme met with limited
      success in improving compliance with the guidelines. Further work is needed to
      ensure awareness of these guidelines, with ongoing monitoring to ensure best
      practice and optimal patient outcome.

PMID- 16098333
TI  - Interhospital trauma transfers: room for improvement?

PMID- 16098334
TI  - The effectiveness of orthopaedic trauma theatres in decreasing morbidity and
      mortality: a study of 701 displaced subcapital hip fractures in two trauma
      centres.
AB  - In countries with universal health care systems patients frequently wait days for
      their "emergency" surgery. A general trend in orthopaedic traumatology is the
      advent of daily, dedicated orthopaedic trauma theatres. Availability of trauma
      theatres is believed to decrease morbidity and mortality, but this remains
      unproven. A retrospective review comparing morbidity and mortality outcomes
      between two similar level-one trauma centres (one without a dedicated trauma room
      system) was undertaken. We reviewed 701 elderly patients receiving
      hemiarthroplasties for displaced subcapital hip fractures over a 76-month period.
      Patients were similar between centres in terms of age, gender ratio and
      comorbidities. Statistically significant differences were found favouring the
      dedicated trauma room system with approximately half the operative delay and post
      operative morbidity. A trend towards decreased mortality was also seen. This
      study supports the use of regular orthopaedic trauma theatres in tertiary care
      institutions.

PMID- 16098335
TI  - An experimental study of pressure-volume dynamics of casting materials.
AB  - Casting materials are commonly used in a trauma and post-operative setting in
      orthopaedic practice. Swelling after trauma or surgery is universal, hence, the
      importance of understanding the pressure-volume dynamics of various materials
      commonly used for casting. This study attempts to define the pressure response of
      casts made from three commonly used materials to increasing volume, using a
      cylindrical model cast. Plaster of Paris (PoP), rigid fibreglass and semi-rigid
      non-fibreglass (Softcast) were chosen for comparison. Softcast had the best
      compliance and rate dependency characteristics, accommodating significantly more
      volume of fluid compared to plaster of Paris or Rigid fibreglass material. The
      latter two had similar compliance. All three materials demonstrated stress
      relaxation which is of advantage in reducing peak pressures for a given volume
      change. This study shows that the casting materials behave in a viscoelastic
      manner, which allows them to accommodate more volume change than would otherwise
      be possible. The use of semi-rigid material may be safer than other materials as
      far as response to swelling (volume expansion) is concerned.

PMID- 16098336
TI  - The effect of transfixion wire crossing angle on the stiffness of fine wire
      external fixation: a biomechanical study.
AB  - To analyse the effect of transfixion wire-crossing angle on the stiffness of fine
      wire external fixation, a laboratory investigation using a fibreglass tibia fixed
      into an idealised fixator was performed with a servohydraulic test frame. Load
      deformation behaviour was compared at the different wire-crossing angles (30
      degrees -90 degrees ) under identical conditions of central axial compression,
      medial compression-bending, posterior compression-bending, posteromedial
      compression-bending, and torsion. Stiffness values were calculated from the load
      deformation and torque-angle curves. The increase in wire-crossing angle led to
      an overall increase in the stiffness, except medial bending stiffness. The wire
      crossing angle of 90 degrees provided significantly greater stiffness than all
      other angles in all load configurations (p<0.05) except medial bending. In medial
      bending, the wire-crossing angle of 30 degrees provided significantly greater
      stiffness than all the other angles (p<0.05). Increasing wire-crossing angle from
      30 degrees to 90 degrees contributed to an overall increase of 75% in external
      fixation stiffness, which included axial, torsional, and bending stiffness, but
      bending stiffness was a function of the wire positioning with respect to the
      loading axis. Therefore, using the widest possible wire-crossing angle and
      placing wires as close to the loading plane as possible can increase the
      stiffness of external fixation.

PMID- 16098337
TI  - Postero-medial fracture of the talus in a skeletally immature adolescent treated
      by internal fixation.

PMID- 16098338
TI  - A novel method of applying a split cast.
AB  - Split plaster casts have been shown to be better than back slabs at accommodating
      increasing intracompartmental pressure due to swelling. Splitting a wet plaster
      cast can be time consuming and difficult both for the patient and the medical
      staff. We describe a novel method of applying a split plaster of Paris cast,
      which is safe, quick, convenient and inexpensive.

PMID- 16098341
TI  - Ultrasound of the liver.
AB  - This article summarizes the recent advances in ultrasound imaging of the liver,
      especially contrast-enhanced imaging. Contrast-enhanced ultrasound has
      dramatically changed the role of ultrasound in liver tumor characterization,
      detection, and other applications. Available ultrasound contrast agents, agents
      under development, contrast-specific imaging techniques, and its applications in
      liver imaging are discussed.

PMID- 16098342
TI  - Multidetector row CT of the liver.
AB  - CT has always played a major role in the imaging of the liver despite continuous
      challenge by ultrasound and MR imaging. Introduction of multidetector row CT
      technology has helped CT to excel in its already established indications and has
      expanded its capabilities by adding new clinical indications, such as CT
      angiography or liver perfusion. This article discusses the advantages of
      multidetector row CT scanners in liver imaging, examines the guidelines to
      improve image quality by optimizing scanning protocols and contrast
      administration strategies, and reviews the current and potential clinical
      applications.

PMID- 16098343
TI  - Applications of PET in liver imaging.
AB  - Fluorodeoxyglucose PET (FDG-PET) imaging has an important role in determining if
      there are metastases to the liver and whether disease has spread beyond the
      liver. Such information is critical for planning surgical resections of liver
      metastases. The ability of FDG-PET quantitatively to estimate metabolic rates
      makes it an important tool for monitoring. With increasingly broad indications
      for FDG-PET imaging, it is expected that FDG-PET (and PET-CT) of the liver will
      play a growing and increasingly important role in detecting and monitoring
      treatment of tumors involving the liver.

PMID- 16098344
TI  - MR imaging of the liver.
AB  - MR imaging is establishing a role as a primary diagnostic technique, with
      increasing evidence showing MR imaging to have advantages over CT regarding
      diagnostic sensitivity and specificity for many pathologies of solid organs, bile
      and pancreatic ducts, bowel, peritoneum, and retroperitoneum. In addition, there
      are increasing concerns regarding the risks of radiation and iodinated contrast
      associated with CT imaging of the abdomen. The incidence of contrast-induced
      nephropathy associated with iodinated contrast used for CT scanning is difficult
      to ascertain because reporting is spurious and variable in interpretation.

PMID- 16098345
TI  - Contrast agents for MR imaging of the liver.
AB  - Imaging of the liver is performed most often to detect and characterize focal
      liver lesions. MR imaging has been the method of choice to assess focal liver
      lesions accurately. Nonspecific intravenous contrast agents have been used for
      routine abdominal MR imaging protocols including liver imaging. Over the last 10
      to 15 years new contrast agents have been developed that combine the excellent
      contrast resolution of MR imaging with improved tissue specificity. This article
      reviews various contrast agents that are in clinical use for liver MR imaging and
      discusses their potential clinical role.

PMID- 16098346
TI  - Local therapeutic treatments for focal liver disease.
AB  - Patients diagnosed with primary hepatic malignancies or metastases to the liver
      remain a difficult population to treat. A small percentage of these people can
      undergo surgical resection or transplantation. The remaining nonsurgical
      aggregate does not often benefit from conventional radiation and chemotherapy;
      minimally invasive means either to cure or palliate these patients are a
      requirement for complete cancer care. This article discusses image-guided local
      therapies used to treat this difficult patient population, focusing predominantly
      on radiofrequency ablation.

PMID- 16098347
TI  - Pre-, peri-, and posttreatment imaging of liver lesions.
AB  - This article provides an overview of current treatment approaches in patients
      with primary or secondary liver diseases. Emphasis is placed on MR imaging prior,
      during, and after various treatments, including liver resection, systemic
      chemotherapy, transcatheter arterial chemoembolization, ablative therapies, and
      liver transplantation. Findings described for MR imaging are directly applicable
      to findings for CT and potentially contrast-enhanced ultrasound. The authors'
      description, however, will deal mainly with MR imaging as this is the their
      preferred approach due to diagnostic accuracy and patient safety, and the
      findings are most demonstrative on MR imaging.

PMID- 16098348
TI  - Hepatic imaging: comparison of modalities.
AB  - This article describes a number of aspects of liver imaging, including the main
      reasons for imaging of the liver; the current status and recent developments of
      ultrasound, CT, MR imaging, and PET; and the role of these imaging modalities in
      the assessment of hepatic abnormalities. Finally, a systematic review of the
      current relevant literature on studies that compare modalities is presented, and
      a strategy for the work-up of liver diseases is proposed.

PMID- 16098349
TI  - Performance-enhancing supplement use in patients with testicular cancer.
AB  - OBJECTIVES: To identify supplement use among patients diagnosed with testicular
      cancer. The incidence of testicular cancer has increased, as has supplement use,
      including those designed specifically for exercise performance enhancement.
      METHODS: A questionnaire was administered to patients with testicular germ cell
      cancer treated at our institution between 1990 and 2004. This survey addressed
      the use of supplements before, during, and after the diagnosis of cancer.
      RESULTS: Of the 129 patients who completed the questionnaire, 26 (20.1%) used
      some form of supplements, most of which were ingested for exercise performance
      enhancement. The most common supplement taken was protein/amino acids (12.4%)
      followed by creatine (9.3%) and androstenedione (1.6%). The mean duration of
      supplement use was 17.0 months. The mean age of the patients who had used
      supplements was 27.6 years (median 26, range 17 to 47) compared with 35.7 years
      (median 34, range 14 to 76) for patients who had not used supplements. Of the 57
      patients diagnosed before 2000, 9 (16%) reported supplement use and 3 (5%)
      reported creatine use. Of the 72 patients diagnosed during or after 2000, 17
      (24%) reported supplement use and 9 (13%) reported creatine use. CONCLUSIONS:
      Supplement use is common and increasing among patients with testicular cancer.
      The use of exercise performance-enhancing supplements was as great as 20%. Given
      the increasing incidence of testicular cancer, coupled with the widespread use of
      these performance-enhancing supplements in this at-risk group, additional study
      is required to determine what association, if any, exists between the use of
      these substances and the development of testicular cancer.

PMID- 16098350
TI  - Can ureteral stent encrustation analysis predict urinary stone composition?
AB  - OBJECTIVES: To determine the value of mid-infrared spectroscopy (MIRS) of
      ureteral stent encrustations in predicting urinary stone composition. METHODS: A
      retrospective study analyzed the composition of stent encrustations and urinary
      stones by MIRS in patients who had had a stent for ureteral obstruction between
      2001 and 2003. The overall correlation was evaluated. The correlation coefficient
      kappa for agreement between the proportions of each component was calculated.
      RESULTS: A total of 72 stents and 72 stones from 72 patients were analyzed. The
      mean stent indwelling time was 55.5 days (range 14 to 102). The stents had been
      placed for fever (52 cases, 72%), pain refractory to analgesics (15 cases, 21%),
      and impairment of kidney function (5 cases, 7%). The overall correlation between
      stone composition and stent encrustation was 71.4%, excluding biofilm analysis.
      The kappa value was 0.78 for the main component (n = 72; P < 0.0005), 0.61 for
      the secondary component (n = 72; P < 0.0005), and 0.91 for the agreement between
      the composition of encrustations at each end of a stent (n = 30; P < 0.0005).
      CONCLUSIONS: MIRS analysis of stent encrustations is a reliable method of
      predicting stone composition when the stone cannot be retrieved. Systematic MIRS
      analysis of stent encrustations is not recommended but can be very useful in
      clinical situations in which no stone is available.

PMID- 16098351
TI  - Retrograde stenting for obstruction of the renal transplant ureter.
AB  - OBJECTIVES: To present our experience with retrograde stent placement and stent
      exchange for transplant ureteral obstruction. METHODS: A review of our renal
      transplant database was performed to identify all renal transplant patients who
      underwent attempted retrograde ureteral stenting for allograft ureteral
      obstruction or attempted allograft ureteral stent exchange between May 1992 and
      April 2004. A retrospective review was performed. RESULTS: Forty patients
      underwent 52 attempted retrograde ureteral stent placements, and 11 patients
      underwent a total of 27 attempted stent exchanges. In patients with ureteral
      obstruction, the most common clinical signs and symptoms were nausea, vomiting,
      diarrhea, abdominal pain, fever, decreased urine output, edema, and an elevated
      serum creatinine. Of the 52 cases of allograft ureteral obstruction and attempted
      retrograde ureteral stent placement, 28 (53.8%) were managed successfully with
      retrograde ureteral stenting. Of the 27 attempted stent exchange procedures, a
      successful exchange was accomplished in 23 cases (85.2%). CONCLUSIONS: Cystoscopy
      with retrograde allograft stent placement is a reasonable first approach to the
      management of transplant ureteral obstruction and is successful in more than one
      half of cases.

PMID- 16098354
TI  - Renal cell carcinoma with tumor thrombus extending above diaphragm: avoiding
      cardiopulmonary bypass.
AB  - OBJECTIVES: Renal cell carcinoma with a tumor thrombus extending into the
      supradiaphragmatic inferior vena cava (IVC) and right atrium represents a
      challenge to the surgical team. We describe a technique that can be used to
      resect these tumors safely through a transabdominal approach without recourse to
      cardiopulmonary bypass (CPB) or entry into the thoracic cavity. METHODS: Between
      May 1997 and August 2004, 59 patients (mean age 61 years) underwent surgical
      resection of a renal tumor extending into the IVC by techniques developed with
      the intention to avoid sternotomy and CPB. In 7 patients (12%), the tumor
      thrombus extended into the supradiaphragmatic IVC and right atrium. Complete
      surgical resection was successful through a transabdominal approach without CPB
      in all 7 of these patients. RESULTS: In the 7 patients who underwent the
      described technique, the median age was 71 years (range 51 to 80). The mean
      operative time was 7 hours, 47 minutes. The mean estimated blood loss was 2514 mL
      (range 500 to 6000). The mean number of blood units transfused was 4.7 (range 0
      to 11). One patient died in the immediate postoperative period of cardiac
      arrhythmia. The median follow-up was 11.1 months, and 5 patients were disease
      free. CONCLUSIONS: In select cases, renal cell carcinoma extending into the
      supradiaphragmatic IVC and right atrium can be resected without the use of CPB.
      We describe our technique.

PMID- 16098355
TI  - Urothelial carcinoma of the upper urinary tract: comparison between the WHO/ISUP
      1998 consensus classification and WHO 1999 classification system.
AB  - OBJECTIVES: To compare the usefulness of World Health Organization
      (WHO)/International Society of Urological Pathologists 1998 consensus
      classification with the WHO 1999 classification in a large series of urothelial
      tumors of the upper urinary tract. Only a few bladder tumor studies have compared
      these systems. METHODS: A clinical and histopathologic review was performed of
      all patients diagnosed in western Sweden between 1971 and 1998 with renal pelvic
      or ureteral carcinoma. We selected 555 surgically treated patients who all had a
      urothelial tumor on review of the pathologic findings and no bladder tumor before
      diagnosis of the upper tract tumor. The median follow-up was 52 months. Disease
      specific survival was calculated using Kaplan-Meier estimates. RESULTS: A total
      of 349 patients had Stage pTa, pT1, or pT2 tumor, with a 5-year disease-specific
      survival rate of 95%, 80%, and 79%, respectively. No significant difference was
      found in the prognosis among papillary urothelial neoplasm of low malignant
      potential and low-grade and high-grade tumors of the same stage. Nor was a
      difference found among papillary urothelial neoplasm of low malignant potential
      and grade 1, 2, and 3 tumors. Of the 349 patients, 171, all with high-grade Stage
      pT3 tumors, had a 35% disease-specific survival rate. Of these tumors, 38 were
      grade 2 and 133 were grade 3, with a survival rate of 49% and 25%, respectively
      (P <0.0037). All 35 pT4 tumors were high grade, and no patient survived past 30
      months. CONCLUSIONS: Tumor stage was a very strong predictor of prognosis in this
      series of patients treated with open surgery. The tumor grade had little
      additional prognostic value, although a small advantage was found for the WHO
      1999 classification, but only for high-grade, Stage pT3 tumors.

PMID- 16098356
TI  - Laparoscopic partial nephrectomy: is it advantageous and safe to clamp the renal
      artery?
AB  - OBJECTIVES: To compare the outcomes of laparoscopic partial nephrectomy (LPN)
      performed with and without vascular clamping and to evaluate the impact of
      clamping on postoperative renal function. METHODS: A total of 45 patients
      underwent LPN, 29 with and 16 without vascular occlusion. The two groups were
      compared regarding complication rates, blood loss, conversion rates, operative
      time, mean tumor size, and incidence of positive margins. Renal function was
      evaluated by postoperative dimethyl mercaptosuccinic acid scans. RESULTS: The
      mean blood loss was lower when vascular clamping was applied (320 versus 510 mL,
      P <0.05) than when it was not. The conversion rates were similar (10.3% versus
      12.5%), and the mean operative time was shorter in the nonclamped group (115
      versus 126 minutes). Urinary leakage occurred in 2 patients, 1 from each group.
      The mean tumor diameter was 3.2 cm in the clamped and 1.9 cm in the nonclamped
      group (P <0.05). In 2 patients (12.5%) in the nonclamped and 1 patient (3.4%) in
      the clamped group, the surgical margins were focally positive for tumor. The mean
      warm ischemia time was 28 minutes, and dimercaptosuccinic acid scans performed in
      18 patients showed normal ipsilateral renal function (mean relative function
      48%). CONCLUSIONS: LPN without vascular clamping is feasible in selected cases.
      However, clamping of the artery seems to be associated with reduced blood loss
      and a lower incidence of positive margins. Moreover, according to the
      postoperative dimercaptosuccinic acid scan findings, limited warm ischemia does
      not seem to result in permanent renal damage. We suggest that clamping of the
      renal artery should be considered during LPN, even for very small, superficial
      tumors.

PMID- 16098357
TI  - Impact of delay to nephroureterectomy for patients undergoing ureteroscopic
      biopsy and laser tumor ablation of upper tract transitional cell carcinoma.
AB  - OBJECTIVES: To investigate whether a delay in nephroureterectomy for patients
      with transitional cell carcinoma of the upper urinary tract owing to
      ureteroscopic biopsy and/or laser tumor ablation affects postoperative disease
      status. METHODS: Of 155 patients diagnosed with upper tract transitional cell
      carcinoma at our institution from 1993 to 2003, 121 underwent nephroureterectomy.
      We compared the postoperative disease status of patients who underwent
      nephroureterectomy on the basis of positive cytology findings and filling defect
      on contrast imaging (no ureteroscopy; n = 34) to patients who underwent
      nephroureterectomy after ureteroscopic biopsy (n = 75) and patients who underwent
      nephroureterectomy after ureteroscopic biopsy and laser tumor ablation (n = 12).
      RESULTS: At a mean follow-up of 38.7 months, 29 (85.3%) of 34 patients who
      underwent nephroureterectomy on the basis of contrast imaging and urinary
      cytology alone were disease free compared with 61 (81.3%) of 75 patients who
      underwent ureteroscopic biopsy before nephroureterectomy (P = 0.18). The mean
      time from biopsy to nephroureterectomy for these 75 patients was 28 days, and the
      mean follow-up after nephroureterectomy was 40.1 months. Finally, 10 (83.3%) of
      12 patients who underwent ureteroscopic biopsy and laser tumor ablation before
      nephroureterectomy were disease free at a mean follow-up of 37.2 months. The mean
      time from ureteroscopic biopsy to nephroureterectomy in this group was 196 days.
      No significant difference was found in the postoperative disease status between
      patients undergoing nephroureterectomy after ablation and those who proceeded to
      nephroureterectomy after endoscopic biopsy or those who did not undergo
      ureteroscopy before nephroureterectomy (P = 0.16). CONCLUSIONS: Ureteroscopy with
      biopsy and/or tumor ablation before nephroureterectomy did not adversely affect
      the postoperative disease status.

PMID- 16098358
TI  - Laparoscopic mobilization of neovagina to assist secondary ileal vaginoplasty in
      male-to-female transsexuals.
AB  - OBJECTIVES: To describe 3 cases of successful laparoscopically assisted vaginal
      reconstruction using an ileal segment in patients with complete neovaginal
      stenosis. METHODS: We evaluated 5 male-to-female transsexual patients who
      required laparoscopic-assisted vaginal replacement for complete neovaginal
      stenosis after sex reassignment surgery. We performed complete laparoscopic
      vaginal isolation and mobilization, external configuration of the vagina, and
      laparoscopic-assisted vaginal anastomosis. RESULTS: No intraoperative
      complications occurred, and laparotomy conversion was not necessary. The mean
      length of the neovagina at the first postoperative visit was 13 cm. At a mean
      follow-up of 14 months, all patients were sexually active and completely
      satisfied with the operation. CONCLUSIONS: Our results have confirmed the
      feasibility of laparoscopic perineal neovagina construction by ileal colpoplasty.
      The cosmetic, functional, and anatomic results were encouraging. Isolated ileal
      segments provided excellent tissue for vaginal replacement, resulting in
      excellent patient satisfaction and relatively low morbidity. Furthermore, we
      report a modified surgical approach to conventional ileal vaginoplasty according
      to the Monti channel principle.

PMID- 16098360
TI  - Bladder cancer screening and monitoring of 4,4'-methylenebis(2-chloroaniline)
      exposure among workers in Taiwan.
AB  - OBJECTIVES: Transitional cell carcinoma of the urinary bladder is associated with
      occupational exposure to 4,4'-methylenebis(2-chloroaniline) (MBOCA). A program to
      monitor MBOCA levels in the work environment and to screen for bladder cancer was
      performed at four MBOCA manufacturing factories. METHODS: The U.S. Occupational
      Safety and Health Administration analytic method No. 24 was adopted in this study
      to measure air MBOCA concentrations. A total of 70 MBOCA-exposed workers and
      another 92 nonexposed workers were recruited for screening. Urine occult blood
      tests, urine cytology, tests for the urine tumor marker nuclear matrix protein,
      and abdominal ultrasonography were performed in all patients. Intravenous
      urography and cystoscopy were used to confirm the presence of bladder cancer.
      RESULTS: The air concentration of MBOCA was greatest in the purification area
      (0.23 to 0.41 mg/m3), followed by the washing area (less than 0.02 to 0.08 mg/m3)
      and neutralization area (less than 0.05 to 0.06 mg/m3). This study identified a
      current worker with proved bladder cancer. In addition, we also identified 1
      worker with suspected malignant cells on urine cytology and 1 worker with
      atypical cytology combined with gross hematuria. Although the prevalence of
      atypical urinary cells and the nuclear matrix protein 22 tumor marker was not
      significantly different between the MBOCA-exposed workers and nonexposed workers
      as a whole or when grouped by sex, the prevalence of positive occult blood was
      marginally significantly (P = 0.055) greater in male exposed workers (18%) than
      in male nonexposed workers (7%). CONCLUSIONS: The findings of this study support
      the conclusions from other studies that MBOCA is potentially carcinogenic to
      humans. Control measures are needed to prevent overexposure from inhalation and
      skin absorption.

PMID- 16098361
TI  - Symptom deterioration during treatment and history of AUR are the strongest
      predictors for AUR and BPH-related surgery in men with LUTS treated with
      alfuzosin 10 mg once daily.
AB  - OBJECTIVES: To assess the predictors of acute urinary retention (AUR) and/or
      surgery related to benign prostatic hyperplasia (BPH) in 3514 men complaining of
      lower urinary tract symptoms and treated for 6 months with the selective alpha1
      blocker alfuzosin at 10 mg once daily. METHODS: The impact of baseline (age,
      prior AUR, prostate-specific antigen tertiles, lower urinary tract symptoms
      severity, and bother score) and dynamic (International Prostate Symptom Score
      [IPSS] worsening of 4 points or greater and bother greater than 3 during
      treatment) variables on the risk of AUR/BPH-related surgery was assessed using
      Kaplan-Meier curves and log-rank tests. Associated hazard ratios (HRs) and 95%
      confidence intervals (CIs) were calculated using Cox proportional hazard models.
      RESULTS: Of the 3514 men analyzed, 140 (4%) experienced a first episode of
      conservatively managed AUR before inclusion. Of those 140 men, 5 (3.6%) had AUR
      relapse during alfuzosin treatment and 6 (4.3%) underwent BPH-related surgery. Of
      those 3374 men without prior AUR, 19 (0.6%) experienced AUR during treatment and
      41 (1.2%) underwent BPH-related surgery. During treatment, the most important
      predictors of AUR were prior AUR (HR 6.35, 95% CI 2.31 to 17.40; P < 0.01), IPSS
      worsening of 4 or greater (HR 3.34, 95% CI 1.11 to 9.99; P = 0.03), and bother
      score greater than 3 (HR 3.32, 95% CI 1.29 to 8.53; P < 0.01) at endpoint. Other
      variables (age, PSA, baseline IPSS, and bother) had much less predictive value.
      Similar results were observed regarding the risk of AUR and/or BPH-related
      surgery. CONCLUSIONS: The results of this 6-month real life practice study
      suggest that prior AUR and symptom deterioration during treatment with alfuzosin
      10 mg once-daily (IPSS worsening of 4 or more points, bother score greater than
      3) were the strongest predictors of AUR and AUR/BPH-related surgery in men with
      lower urinary tract symptoms.

PMID- 16098362
TI  - Androgen receptor, Ki67, and p53 expression in radical prostatectomy specimens
      predict treatment failure in Japanese population.
AB  - OBJECTIVES: To evaluate multiple known prognostic markers in localized prostate
      cancer using tissue microarrays in Japanese patients. Molecular studies have
      suggested that ethnicity influences prostate tumor biology. METHODS: Specimens
      were studied from 52 patients who underwent radical surgery at our institution
      between 1997 and 2001 without neoadjuvant hormonal therapy and with three or more
      available and complete cancer spots. Ki67, p53, and androgen receptor antigen
      expression were examined. Immunohistochemical scores were compared with outcomes
      of chemical relapse as monitored using prostate-specific antigen. RESULTS:
      Pathologic tumor classification (P = 0.047), World Health Organization score (P =
      0.026), World Health Organization histologic grade (P = 0.026), and surgical
      margin status (P = 0.018) were significant conventional clinicopathologic
      variables for predicting biochemical failure. The tissue microarray Gleason sum
      (P = 0.038), tissue microarray primary Gleason grade (P = 0.013), Ki67 labeling
      index (P < 0.0001), p53 (P = 0.0097), and androgen receptor (P = 0.0113) antigen
      expression also were significant. Moreover, surgical margin status and Ki67
      labeling index were independently associated with treatment failure. CONCLUSIONS:
      Especially together, the Ki67 labeling index and p53 and androgen receptor
      expression in localized prostate cancer often predicted postoperative progression
      in Japanese patients.

PMID- 16098363
TI  - Quality of life after radical treatment of prostate cancer: validation of the
      Italian version of the University of California-Los Angeles Prostate Cancer
      Index.
AB  - OBJECTIVES: To validate an Italian version of the University of California-Los
      Angeles Prostate Cancer Index (UCLA-PCI). METHODS: Men with prostate cancer
      treated with radical retropubic prostatectomy (RRP) or external beam radiation
      (EBR) were retrospectively selected. Each subject was asked to complete the UCLA
      PCI short form and the 36-item short-form health survey (SF-36) questionnaires
      (principal sample); a subgroup completed both questionnaires twice (retest
      sample). A linguistic translation and validation was performed. Psychometric
      properties were analyzed. RESULTS: A total of 595 men were included in the study:
      394 from the Department of Urology (treated with RRP) and 201 from the Department
      of Radiotherapy (treated with EBR). Of these, 75 patients (50 from the RRP group
      and 25 from the EBR group) were selected as the retest cohort. Internal
      consistency reliability of the SF-36 and UCLA-PCI for the primary sample of the
      surgery and radiotherapy populations ranged from 0.82 to 0.94; the mean values of
      sexual function were superior in the principal urology group, whereas the
      principal radiotherapy group demonstrated superior mean values of urinary
      function and urinary bother. A strong correlation between urinary function and
      sexual and bowel function, and between urinary function and all bother scales,
      was reported only for patients treated with RRP. The expected correlation between
      sexual function and sexual bother was reported for the EBR group but not for the
      RRP group. CONCLUSIONS: Our study demonstrated the excellent psychometric
      properties of the Italian version of the UCLA-PCI; the Italian version of the
      UCLA-PCI questionnaire will allow cross-cultural comparative studies in men with
      prostate cancer.

PMID- 16098364
TI  - Impact of multiple biopsy cores on predicting final tumor volume in prostate
      cancer detected by a single microscopic focus of cancer on biopsy.
AB  - OBJECTIVES: To compare the impact that the number of biopsy cores have on final
      pathologic findings when minimal disease is detected at biopsy. Discordance has
      been noted between transrectal ultrasound-guided biopsy results and tumor volume
      even when minimal amounts of tumor are found on biopsy. METHODS: We identified
      patients who had undergone radical retropubic prostatectomy for a single
      microscopic focus of adenocarcinoma from a prospectively maintained surgical
      database. Patients were stratified into two groups: those with six biopsies or
      less and those with seven or more. The Gleason score, margin status, presence of
      extracapsular extension, and percentage of tumor volume were compared. RESULTS: A
      total of 102 patients in our database had a single microscopic focus of
      adenocarcinoma detected by needle biopsy. Of these patients, 65 underwent six or
      fewer biopsies and 37 underwent seven or more at transrectal ultrasonography. Of
      the 37 patients in group 2, 27 (73%) had a final tumor volume of less than 5%
      compared with 24 (37%) of 65 patients in group 1 (P = 0.002). Of the group 2
      patients, 15 (75%) with Stage T1c had an estimated tumor volume of less than 5%
      compared with only 11 (34%) in group 1 (P = 0.01). No statistically significant
      difference was noted between the two groups for margin status, presence of
      extracapsular extension, or Gleason score. CONCLUSIONS: A single microscopic
      focus of cancer obtained after multiple cores predicts for a significantly lower
      tumor volume on final pathologic examination across clinical stages. In the
      context of greater tissue sampling, the minimal disease designation may carry
      more predictive value and be a useful parameter in stratifying patients with
      Stage T1c and other good-risk factors with regard to surgical outcome.

PMID- 16098365
TI  - Cross-sectional analysis of sexual function after prostate brachytherapy.
AB  - OBJECTIVES: To assess sexual function after prostate brachytherapy and compare
      outcomes in different age groups. METHODS: This cross-sectional study consisted
      of 96 sexually active patients (mean age 64 years) who underwent iodine-125 seed
      implantation between 1997 and 2003 to treat early-stage prostate cancer (Stage T1
      T2). Patients completed a questionnaire adapted from the validated Rand 36-Item
      Health Survey and the University of California, Los Angeles, Prostate Cancer
      Index. RESULTS: The median follow-up was 2.5 years (range 3 months to 6.2 years).
      The mean value for sexual function was 54.8. The mean score for erectile function
      was 55.0, and the mean score for the ability to reach orgasm was 54.0. No
      significant relationship was found between sexual function and time since
      treatment (P = 0.9897). Pain on orgasm was reported after brachytherapy by 38
      patients (40%) and hematospermia by 16 patients (17%). A negative correlation was
      observed between pain on orgasm and time since treatment (P = 0.021), but no
      significant relationship was found between hematospermia and time since treatment
      (P = 0.427). A significant difference in sexual function was observed between
      patients younger than 60 years and patients older than 60 years (66.3 +/- 7.0
      versus 47.7 +/- 7.2; P = 0.002). CONCLUSIONS: A large variation in sexual potency
      is present after brachytherapy with no significant relationship to the time since
      treatment. Age is an indicator of sexual function after brachytherapy, with
      younger patients experiencing less sexual dysfunction than older patients. Other
      aspects of sexual function (pain on orgasm, hematospermia) are also significant
      side effects of brachytherapy and must be considered in the treatment decision
      for low-risk prostate cancer.

PMID- 16098366
TI  - The combination of estramustine, vinorelbine, and mitoxantrone in hormone
      refractory prostate cancer: a Phase II feasibility study conducted by the
      Hellenic Cooperative Oncology Group.
AB  - OBJECTIVES: To evaluate the safety profile and therapeutic value of the
      combination of estramustine, mitoxantrone, and vinorelbine in the treatment of
      hormone-refractory prostate cancer. METHODS: Fifty-two patients with hormone
      refractory prostate cancer were included in the study. Median age was 70 years
      (range, 49 to 100 years), World Health Organization performance status ranged
      from 0 to 2. The treatment schedule consisted of estramustine capsules (140 mg 3
      times daily on days 1 to 3 and days 8 to 10 per os), intravenous mitoxantrone (12
      mg/m2 on day 2), and intravenous vinorelbine (25 mg/m2 on day 2 and day 9), given
      in a 3-week cycle. RESULTS: Thirty-one percent of patients with measurable soft
      tissue disease demonstrated an objective response, which included six complete
      and ten partial responses in all involved organs (bone responses not included).
      Twenty-nine patients (56%) had a greater than 50% reduction in serum prostate
      specific antigen level. The median duration of response was 6.9 months, and the
      median survival for all patients was 14.5 months. CONCLUSIONS: The combination of
      estramustine, vinorelbine, and mitoxantrone is safe, well tolerated, and
      relatively active in patients with hormone-refractory prostate cancer.

PMID- 16098367
TI  - Prognostic significance of plasma chromogranin a levels in patients with hormone
      refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study.
AB  - OBJECTIVES: To test the hypothesis that chromogranin A (CgA) levels are
      prognostic in patients with metastatic hormone-refractory prostate cancer (HRPC).
      The extent of neuroendocrine differentiation in prostate cancer correlates with
      aggressive disease and with progression to HRPC. Plasma CgA levels in patients
      with prostate cancer may reflect the extent of the tumor neuroendocrine
      phenotype. METHODS: Pretreatment plasma was collected from 390 patients with
      metastatic HRPC enrolled in the Cancer and Leukemia Group B (CALGB) 9480 trial, a
      study of three different doses of suramin. Plasma CgA levels were determined in
      321 samples in duplicate using a quantitative sandwich immunoassay. The
      proportional hazards model was used to assess the prognostic significance of CgA
      in predicting overall survival. RESULTS: The median plasma CgA level was 12 U/L
      (interquartile range 7.7 to 19.3). In univariate analysis, plasma CgA correlated
      inversely with survival times, with a survival time of 17 months for low CgA
      (less than 12 U/L, 95% CI 14 to 19) compared with 11 months for high CgA (95% CI
      8 to 14, P = 0.014) and at all exploratory cutpoints, including CgA of 9.5 U/L or
      less versus greater than 9.5 U/L, with survival of 19 months compared with 12
      months (P = 0.0015). In multivariate models (adjusting for performance status,
      prostate-specific antigen, and lactate dehydrogenase), the plasma CgA levels
      remained predictive of overall survival. CONCLUSIONS: These results support the
      hypothesis that serum CgA levels correlate with outcome in patients with HRPC,
      although the clinical significance needs to be established in confirmatory
      studies before incorporation of CgA measurements in clinical practice.

PMID- 16098368
TI  - A novel missense mutation of 5-alpha reductase type 2 gene (SRD5A2) leads to
      severe male pseudohermaphroditism in a Turkish family.
AB  - OBJECTIVES: To analyze the steroid 5-alpha reductase type 2 gene (SRD5A2) in 2
      siblings with severe male pseudohermaphroditism suspected to have 5-alpha
      reductase deficiency in a Turkish family. METHODS: Two female siblings of a
      family with 7 children were referred to the urology department because of
      bilateral inguinal masses. The patients had presented after birth with ambiguous
      genitalia, but no further diagnostic procedures had been performed, and they were
      raised as girls until the ages of 13 and 15 years. At this time, both had
      striking ambiguity of the genitalia, with a clitoris-like phallus, severely bifid
      scrotum, pseudovaginal perineoscrotal hypospadias, a rudimentary prostate, and
      inguinal testes. Karyotype was 46,XY. Basal and stimulated levels of serum
      testosterone (T), dihydrotestosterone (DHT), and T/DHT ratio indicated 5-alpha
      reductase deficiency. Molecular genetic analysis was performed on
      deoxyribonucleic acid from peripheral blood leukocytes by single-stranded
      conformational polymorphism analysis and direct sequencing. RESULTS: Analysis of
      the SRD5A2 gene revealed a new homozygous missense mutation in exon 2. At codon
      123, we identified a GGA to AGA change resulting in a missense amino acid change
      from glycine to arginine (G123R). Both parents and the 2 healthy sisters and 3
      brothers were all heterozygous at codon 123 for the same mutation. CONCLUSIONS:
      We report a novel homozygous missense mutation in exon 2 of the 5-alpha reductase
      type 2 gene that led to severe undervirilization in 2 siblings.

PMID- 16098369
TI  - Surgical technique to correct complex ureterointestinal stricture with
      defunctionalized limb of Turnbull stoma.
AB  - We describe a novel technique to repair a long ischemic ureterointestinal
      stricture using the defunctionalized limb of a Turnbull stoma in a patient who
      had previously undergone two attempts at open surgical revision.

PMID- 16098370
TI  - Cryptorchidism and its relationship to testicular neoplasia and microlithiasis.

PMID- 16098371
TI  - Fertility after cryptorchidism: epidemiology and other outcome studies.

PMID- 16098372
TI  - Early-stage penile carcinoma metastasizing to brain: case report and literature
      review.
AB  - Early-stage penile squamous cell carcinoma with subsequent distant metastases is
      rare. We report a case of a 35-year-old man with Stage pT1pN0 penile squamous
      cell carcinoma who underwent circumcision and bilateral inguinal lymphadenectomy.
      Further in the disease course, the patient developed metastases in the kidney,
      adrenal gland, retroperitoneal lymph nodes, lung, and brain. He underwent
      multiple resections, whole brain radiotherapy, and several chemotherapy regimens.
      All these metastases were histologically confirmed. Forty months after the first
      diagnosis, the patient died of thromboembolic complications. This case was unique
      because of the unusual pattern of dissemination, especially the spread to the
      brain.

PMID- 16098373
TI  - NS-398, a selective cyclooxygenase-2 inhibitor, reduces experimental bladder
      carcinoma outgrowth by inhibiting tumor cell proliferation.
AB  - OBJECTIVES: To evaluate the efficacy of the selective cyclooxygenase-2 (COX-2)
      inhibitor NS-398 in treating experimental T24 bladder carcinoma, and to assess
      its effect on tumor cell proliferation and survival and tumor vascularization.
      COX-2 overexpression is frequently observed in bladder carcinoma and has been
      correlated with an increased disease stage and with reduced patient survival.
      METHODS: NS-398 was used to inhibit COX-2 selectively in human T24 bladder
      carcinoma cells. Lentiviral transduction of the firefly luciferase gene allowed
      us to assess the effect of NS-398 on orthotopic bladder carcinoma growth over
      time in a noninvasive manner. Immunohistochemistry on bladder tissue sections was
      performed to determine the effect of NS-398 treatment on tumor cell proliferation
      (Ki-67), apoptosis (cleaved caspase-3), and angiogenesis (von Willebrand factor;
      CD31). RESULTS: T24 cells expressed COX-2 and secreted prostaglandin E2 (PGE2).
      Selective COX-2 inhibition using NS-398 abrogated PGE2 secretion and inhibited
      cell proliferation in vitro in a dose-dependent manner, without affecting cell
      viability. In vivo administration of NS-398 reduced the outgrowth of experimental
      orthotopic T24 bladder carcinoma. This was accompanied by a significant reduction
      in Ki-67-positive tumor cells but not by a reduction in tumor cell viability or
      tumor vascularization. CONCLUSIONS: Selective COX-2 inhibition by NS-398 reduces
      the outgrowth of T24 human bladder carcinoma in an orthotopic mouse model. The
      therapeutic activity was most likely caused by inhibition of tumor cell
      proliferation, rather than by inhibition of angiogenesis or tumor cell survival.

PMID- 16098374
TI  - Measurement of tissue mechanical characteristics to distinguish between benign
      and malignant prostatic disease.
AB  - OBJECTIVES: To investigate the relationship between the morphology and mechanical
      properties of benign and malignant prostatic tissues measured in vitro. METHODS:
      Fresh tissue specimens were collected from patients undergoing transurethral
      resection of the prostate (TURP) for benign or malignant prostatic enlargement.
      Individual TURP chippings underwent immediate mechanical testing by applying a
      dynamic compressive strain to the samples. The amplitude ratio (E*) and phase
      difference (tan delta), measures of tissue elastic and viscous components
      respectively, were derived. Individual sections from the processed specimens
      underwent immunohistochemical staining and computerized image analysis was used
      to measure the morphologic characteristics of each TURP chipping. Linear
      regression analysis was used to assess correlations between morphologic and
      mechanical measurements, and the unpaired t test, assuming equal variances, was
      used to compare the mechanical and morphologic characteristics of benign and
      malignant prostates. RESULTS: Significant differences were noted between the
      morphology of the benign and malignant prostates. Tan delta was significantly
      smaller within the malignant prostates (P = 001). No difference was found between
      the benign and malignant prostates with respect to E*. Within the malignant
      prostates, a strong negative correlation was found between the epithelial tissue
      content and tan delta (R2 = 0.50, P = 0.031). CONCLUSIONS: The results of this
      study showed that measurable differences exist between the mechanical
      characteristics of benign and malignant prostatic tissue and provide further
      evidence that significant correlations exist between prostatic tissue morphology
      and mechanical characteristics. We believe that the ability to quantify prostatic
      tissue mechanical characteristics in vivo may be of clinical benefit in the
      future assessment of prostatic diseases, both benign and malignant.

PMID- 16098375
TI  - Administration of extract of mushroom Phellinus linteus induces prostate
      enlargement with increase in stromal component in experimentally developed rat
      model of benign prostatic hyperplasia.
AB  - OBJECTIVES: To clarify the effect of the mushroom extract Phellinus linteus on
      noncancerous prostate cells using an experimentally developed rat benign
      prostatic hyperplasia model. A growing number of people take some natural herbal
      extracts for maintenance of their health. Among them, the extracts of certain
      mushrooms are believed to have a marked tumoricidal effect but low toxicity for
      normal tissues, and they are being drunk widely in Japan and Korea. However,
      until now, their effect on noncancerous benign prostate growth has not been
      examined. METHODS: The mushroom extract was administered daily for 5 weeks to
      experimentally developed benign prostatic hyperplasia rats. Prostate organ
      weight, histologic composition, and gene expression levels of sex hormone
      receptors, transforming growth factor-beta, vascular endothelial growth factor,
      and endothelial nitric oxide synthase were examined. RESULTS: Prostate weight
      increased significantly by 37% owing to treatment with the mushroom extract (P <
      0.05). In particular, the stromal component of the prostate increased
      significantly by 80% (P < 0.05). A suppression of transforming growth factor
      beta1 expression by 56% was observed with the mushroom extract treatment (P <
      0.05). CONCLUSIONS: We found that the mushroom extract enlarged the prostate. The
      effect was suggested to be on the prostate stroma, which may be involved in
      transforming growth factor-beta1 regulation. Administration of mushroom extract
      should be considered carefully by those with an enlarged prostate.

PMID- 16098376
TI  - Speech and non-speech processing in people with specific language impairment: a
      behavioural and electrophysiological study.
AB  - McArthur and Bishop (2004) found that people with specific language impairment
      (SLI) up to 14 years of age have poor behavioural frequency discrimination (FD)
      thresholds for 25-ms pure tones, while people with SLI upto 20 years of age have
      abnormal auditory N1--P2--N2 event-related potential (ERP) responses to the same
      tones. In the present study, we extended these findings to more complex non
      speech and speech sounds by comparing younger (around 13 years) and older (around
      17 years) teenagers with SLI and controls for their behavioural FD thresholds and
      N1-P2 ERPs to 25 and 250-ms pure tones, vowels, and non-harmonic complex tones.
      We found that a subgroup of people with SLI had abnormal responses to tones and
      vowels at the level of behaviour and the brain, and that poor processing was
      associated with the spectral complexity of auditory stimuli rather than their
      phonetic significance. We suggest that both the age of listeners and the
      sensitivity of psychoacoustic tasks to age-related changes in auditory skills may
      be crucial factors in studies of sound processing in SLI.

PMID- 16098377
TI  - Repetitive transcranial magnetic stimulation may induce language switching in
      bilingual patients.
AB  - The dorsolateral prefrontal cortex (DLPFC) may participate in the process of
      language switching in multilingual individuals. We present two cases of bilingual
      patients who experienced unexpected language switching after receiving high
      frequency, repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC
      as a treatment for major depression. These preliminary findings support the role
      of the DLPFC in language switching in polyglots and highlight the potential value
      of rTMS for non-invasively investigating language function in humans. Further
      investigation is warranted.

PMID- 16098378
TI  - Symbol-string sensitivity and adult performance in lexical decision.
AB  - In this study of adult readers, we used a symbol-string task to assess
      participants' sensitivity to the position of briefly presented, non-alphabetic
      but letter-like symbols. We found that sensitivity in this task explained a
      significant proportion of sample variance in visual lexical decision. Based on a
      number of controls, we show that this relationship cannot be explained by other
      factors including: chronological age, intelligence, speed of processing and/or
      concentration, short term memory consolidation, or fixation stability. This
      approach represents a new way to elucidate how, and to what extent, individual
      variation in pre-orthographic visual and cognitive processes impinge on reading
      skills, and the results suggest that limitations set by visuo-spatial processes
      constrain visual word recognition.

PMID- 16098379
TI  - Past tense formation and comprehension of passive sentences in Parkinson's
      disease: evidence from Greek.
AB  - The present study investigates the production of regular and irregular verbs in
      the past tense and the comprehension of passive sentences by Greek-speaking PD
      patients, and compares their behavior to that of normal speakers. Although the
      two groups manifest large scale differences at all the above constructions, the
      behavior of PDs is not different at regular vs. irregular past tense formation
      neither did we obtain strong evidence that they do not comprehend passives, most
      importantly, they certainly do not perform at chance. On the basis of the above,
      we conclude that there are no indications for a clearly linguistic deficit of the
      PD group, hence, their difference with the control group should be attributed to
      other factors, such as the computational demands of the tasks.

PMID- 16098380
TI  - Serial order and consonant-vowel structure in a graphemic output buffer model.
AB  - We review features of the spelling errors of dysgraphic patients with "Graphemic
      Buffer Disorder" (GBD). We argue that the errors made by such patients suggest
      the breakdown of a system used to generate serial order in the output stages of
      spelling production, and we develop a model for this system based on an existing
      theory of sequential behaviour--"Competitive Queuing." We show that constraints
      on response categories may be straightforwardly applied during sequence
      production in such a model, and this enables us to account for the preservation
      of consonant-vowel status in the spelling errors of GBD patients. When the
      sequence generation process is disrupted by the addition of random noise the
      model shows the major features of GBD. The results are compared in detail against
      data from a number of patients.

PMID- 16098381
TI  - Understanding text after severe closed-head injury: assessing inferences and
      memory operations with a think-aloud procedure.
AB  - A think-aloud method was used to examine the content of information available to
      working memory during narrative comprehension in a CHI population. Twenty severe
      CHI participants (>1 year post-injury) and 20 controls talked aloud after they
      read each sentence of story narratives. Trabasso and Magliano's (1996a) verbal
      protocol analysis was then used to code for the production of inferential and non
      inferential clauses and the memory operations that supported inferential clause
      production. We found that CHI and control groups produced a comparable number of
      clauses, that inferences dominated narrative comprehension, and that both groups
      produced more explanatory inferences than predictive or associative inferences.
      Despite these qualitative similarities, the CHI group demonstrated poorer
      comprehension, generated proportionately fewer inferences, relied less on
      retrieval as a memory source for explanatory inferences, and produced more non
      inferential clauses and associative inferences.

PMID- 16098382
TI  - Speech motor programming in hypokinetic and ataxic dysarthria.
AB  - It is widely accepted that the cerebellar and basal ganglia control circuits
      contribute to the programming of movement. Converging evidence from neuroimaging,
      limb control, and neuropsychological studies suggests that (1) people with
      cerebellar disease have reduced ability to program movement sequences in advance
      of movement onset and (2) people with Parkinson's disease are unable to maintain
      a programmed response or to rapidly switch between responses. Despite a
      substantial supporting literature, no studies have addressed these potential
      areas of speech programming disruption for speakers with ataxic and hypokinetic
      dysarthria. Control participants and adults with dysarthria completed speech
      reaction time protocols designed to capture these aspects of utterance
      preparation. Results provided initial support for processing deficits in speakers
      with ataxic and hypokinetic dysarthria that are separable from motor execution
      impairments.

PMID- 16098383
TI  - REVERSAL and PROVE-IT: are clinically oriented trials really better than "pure"
      scientific studies?
AB  - Recently, two large randomised clinical trials compared the effects of standard
      and intensive lipid-lowering treatment (Pravastatin 40 mg vs. Atorvastatin 40 mg
      b.i.d.) on patient prognosis after acute coronary syndromes--the Pravastatin or
      Atorvastatin Evaluation and Infection Therapy (PROVE-IT), and on the
      atherosclerosis regression--the Reversing Atherosclerosis with Aggressive Lipid
      Lowering (REVERSAL). Undoubtedly, the event-rate reduction and the
      atherosclerosis regression associated to intensive hypocholesterolemic treatment
      in these studies are impressive, however we would like to highlight some
      methodological concerns raised by both trials, more clinically oriented than
      planned to give rigorous answers to the scientist. The main problems of both
      studies are that they compare the effects of statins with different pleiotropic
      and pharmacokinetic properties and that the metabolic disorders that affect the
      studied patients have not been clearly described. Moreover, it is unclear if the
      cardiovascular disease history length was similar in the two treatment groups as
      well as the length and dosage of statin treatment of the about 25% of patients
      taking statins before the enrollment. Waiting for studies comparing the effects
      of low and high dosages of the same statin or the high dosage of two similarly
      potent and rapid lipid-lowering effect (as for instance atorvastatin and
      rosuvastatin), prudence has to be applied in the interpretation (and even more in
      the application) of these large and expensive study results, that have yet only
      confirmed the relevance of a more intensive lipid-lowering treatment in all
      patients affected by atherosclerosis-based coronary syndromes.

PMID- 16098384
TI  - The reliability of short-term measurements of heart rate variability.
AB  - Short-term assessment of heart rate variability (HRV) is a non-invasive technique
      to examine ANS function. Within the literature, HRV is commonly referred to as a
      reliable measurement technique. The aim of this review was to assess the accuracy
      of this description based upon a comprehensive review of the available data
      concerning reliability of short-term HRV measures. Reviewing only studies using
      appropriate statistical analyses, it was determined that reliability coefficients
      for HRV measures were highly varied. Coefficients of variation ranged from <1% to
      >100%. Similar variation was found in studies using the intraclass correlation
      coefficient values, and limits of agreement. Reliability coefficients reported
      displayed some distinct patterns. Firstly, where measurements were made during
      interventions such as tilt or pharmacological stimulation, reliability was poorer
      than when HRV was measured at rest. Secondly, clinical populations displayed
      poorer reliability than healthy subjects. There was little effect of test-retest
      duration on reliability and although no single HRV measurement appeared less
      reliable than another, there was evidence that optimal data collection conditions
      for specific frequency domain measures exist. Describing HRV as a reliable
      measurement technique appears to be a gross oversimplification, as results of
      reliability studies are heterogeneous, and dependent on a number of factors.
      Further studies are required, particularly in clinical populations to assess HRV
      reliability. Authors should refer to coefficients from similar populations
      measured under similar conditions when making future sample size calculations.

PMID- 16098385
TI  - Calcium sensitizer agents: a new class of inotropic agents in the treatment of
      decompensated heart failure.
AB  - The clinician's primary objective in treating a patient with decompensated heart
      failure is rapid and effective stabilization. This goal often is achieved through
      the use of inotropic support. Classic inotropic agents (beta-adrenergic agonists
      and phosphodiesterase III inhibitors) can provide short-term hemodynamic
      benefits, but their long-term use has been correlated with poor survival rates.
      Calcium sensitizers comprise a new drug class that offers hemodynamic and
      symptomatic improvements without increasing cAMP and intracellular calcium
      concentrations. These agents enhance contractility without a concurrent increase
      in the risk of cardiac events and thus represent a significant improvement over
      classic positive inotropic agents. Levosimendan is the most potent calcium
      sensitizer to date, exhibiting a unique dual mechanism of action that combines a
      positive inotropic action mediated via calcium sensitization and a vasodilator
      property via ATP-dependent potassium channels. Available clinical data suggest
      that calcium sensitizer agents represent a promising class of inotropic agents in
      a field that has seen few advances in recent decades.

PMID- 16098386
TI  - Safety of coronary angioplasty to chronic total occlusions.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) of chronic total occlusions
      (CTO) is not performed routinely in some centres due to concerns of low
      procedural success rates and high rates of short-term complications. This
      retrospective study examines the safety of PTCA to CTO in 100 consecutive cases
      compared to 100 matched controls. Success rate was 79% for CTO versus 98% for
      controls (p<0.001), however 5% of CTO patients had a cardiac enzyme rise compared
      to 13% of controls (p<0.05) and 0% of CTO patients compared to 6% of controls had
      a significant enzyme rise (p=0.03). These results suggest that PTCA to CTO can be
      carried out successfully in the majority of patients with only a relatively small
      risk of myocardial necrosis.

PMID- 16098387
TI  - Carriers of three polymorphisms of cholesteryl ester transfer protein gene are at
      increased risk to coronary heart disease in a Chinese population.
AB  - BACKGROUND: The cholesteryl ester transfer protein (CETP) is a key participant in
      the reverse transport of cholesterol from the peripheral tissue to the liver and
      the polymorphism in the CETP gene may therefore alter the susceptibility to
      coronary heart disease (CHD). The aim of the present study was to screen the CETP
      gene for new single nucleotide polymorphisms (SNPs) and to determine whether SNPs
      at important cholesterol metabolism gene loci might exert effects on the risk to
      CHD in Chinese. METHODS: Genomic DNA samples were collected from 203 Chinese
      patients with CHD and 209 age- and gender-matched controls. The coding region,
      adjacent intronic sequences and promoter region (totally 5501 bp) of the CETP
      gene were screened based on a combination of polymerase chain reaction,
      denaturing high performance liquid chromatography and DNA sequencing. The
      association of individual single nucleotide polymorphisms with CHD was assessed
      by univariate, multivariate analysis and haplotype analysis. RESULTS: Fifteen
      SNPs were identified in the CETP gene including 12 novel ones, of which, 3 were
      in promoter region, 1 in exon 10, and other 9 in introns. The frequencies of 
      644C, +13054T, 296Q, and 442G alleles were considerably higher, while the
      frequency of +9907A allele lower, in CHD patients than those in controls
      (p=0.016, p=0.043, p=0.006, p=0.006, and p=0.029, respectively). The results of
      individual polymorphism analyses were confirmed by haplotype analysis for the
      combination of these 5 SNPs. The -644A/C, L296Q, and D442G polymorphisms were
      found to be associated with CHD in this Chinese population by multivariate
      analysis (p=0.009, p=0.024, and p=0.007, respectively). The adjusted odds ratio
      for the development of CHD for the -644C allele carriers was 1.63 compared with 
      644AA genotype (95% CI 1.05-2.78; p<0.01), 1.71 for the 296Q allele carriers
      relative to 296LL genotype (95% CI 1.10-2.89; p<0.05), and 1.31 for the 442G
      allele carriers relative to 442DD genotype (95% CI 1.02-2.56; p<0.01),
      respectively. CONCLUSIONS: There is a significant relation between the
      polymorphisms in the CETP gene and the development of CHD, and individuals
      homozygous or heterozygous for the -644C, 296Q, and 442G alleles of the CETP gene
      are at increased risk to develop CHD in this Chinese population.

PMID- 16098388
TI  - The interleukin-6 -174 G>C promoter polymorphism is associated with a higher risk
      of death after an acute coronary syndrome in male elderly patients.
AB  - BACKGROUND: Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are
      key mediators of inflammation and their increased plasma levels are associated
      with acute coronary syndrome (ACS). Polymorphisms in the promoter region of IL-6
      (-174 G>C) and TNF-alpha (-308 G>A) demonstrated to affect gene expression were
      analyzed to test their predictive power for cardiovascular death over one year
      follow-up in elderly male ACS patients. METHODS: We assessed the IL-6 -174 G>C
      polymorphism and TNF-alpha -308 G>A polymorphism in 139 consecutive elderly male
      patients affected by an ACS, such as ST-Elevation (STEMI), No ST-Elevation
      (NSTEMI) Myocardial Infarction and Unstable Angina. The presence of well known
      risk factors for Coronary Heart Diseases (CHD) were also assessed in all ACS
      patients. Survival rate was assessed after one year follow-up. RESULTS: We found
      that IL-6 -174 G>C polymorphism is an independent predictor of cardiovascular
      death after an ACS in male patients. In particular ACS patients carrying the IL-6
      -174 C- (GG) genotypes showed a marked increase in one year follow-up mortality
      rate (HR=3.89, 95% CI 1.71-8.86, p=0.001). Moreover CRP serum levels > or = 5.5
      mg/dl (HR= 3.79, 95% CI 1.71-8.42, p=0.001), a history of CHD (HR=2.96, 95% CI
      1.22-7.20, p=0.016) and the absence of statins treatment (HR=3.27, 95% CI 1.17
      9.18, p=0.021), significantly increased one year risk of death in male ACS
      patients. CONCLUSIONS: These data suggest that IL-6 -174 G>C polymorphism can be
      added to other clinical markers in order to identify a subgroup of elderly ACS
      male patients at higher risk of death.

PMID- 16098389
TI  - Age-related changes in aortic valve with emphasis on the relation between
      pressure loading and thickened leaflets of the aortic valves.
AB  - BACKGROUND: The information of the prevalence of TAV and its relation to aortic
      stenosis in a large-scale human population is limited. METHODS: An
      echocardiographic study was performed prospectively in 2850 subjects to determine
      the relationship between age and the thickened aortic valves (TAV). Another
      simulated study was designed to test the hypothesis that the noncoronary leaflet
      may have a greater diastolic loading than the right or left coronary leaflet.
      RESULTS: The prevalence of TAV in this population was 14.4% (410/2850). It was 0%
      in the <39 years old; however, the prevalence of TAV increased progressively with
      age: it was 10.0% in the middle age group, 17.0% in the elderly group, and 53.7%
      in the octogenarian group (Chi-square test for linear trend, chi2=67.10,
      p<0.001). A greater frequency of TAV was noted at noncoronary leaflet (57.0%)
      than at either right (22.3%) or left (20.6%) coronary leaflet (chi2=5.99, df=2,
      p<0.001). The prevalence of aortic stenosis (AS) tended to increase with age (Chi
      square test for linear trend, chi2=37.85, p<0.001). The simulated study
      demonstrated that the sinus of Valsalva without a coronary leaflet had a higher
      pressure loading than that with a coronary leaflet. CONCLUSION: This study
      demonstrates that the prevalences of TAV and AS increase progressively with age.
      A greater frequency of TAV is found at the noncoronary leaflet than at either the
      right or left coronary leaflet. The simulated study supports our hypothesis that
      the noncoronary leaflet may bear a greater pressure loading than either the left
      or right coronary leaflet.

PMID- 16098390
TI  - The dubious value of echocardiographic and plasma ANP measurements in predicting
      outcome of cardioversion in patients with persistent atrial fibrillation.
AB  - Atrial fibrillation (AF) is a common arrhythmia with important therapeutic and
      prognostic implications. An attempt to restore sinus rhythm is considered in most
      patients with AF. The aim of this study was to assess the value of
      echocardiographic examination and plasma atrial natriuretic peptide (ANP)
      evaluation in predicting the outcome of cardioversion and maintenance of sinus
      rhythm in patients with persistent AF. METHODS: Eighty-one consecutive patients,
      aged 62+/-9 years, with AF of duration 4.7 months were subjected to an
      echocardiography examination and ANP assessment before cardioversion. The
      patients were predominantly hypertensive men with moderately enlarged left atrium
      and ejection fraction of left ventricle of about 50%. All patients were in
      controlled AF and had normalized blood pressure. In order to predict the outcome
      of cardioversion, and maintenance of sinus rhythm over a 1 month period, a
      multivariate logistic regression method was performed using the following
      variables: left atrial and left ventricular dimensions, left ventricular ejection
      fraction and plasma ANP levels. RESULTS: Sixty-nine out of the 81 patients were
      successfully converted to sinus rhythm. At 1 month 57 patients remained in sinus
      rhythm. There were no statistical differences between sinus rhythm and AF group
      in baseline ANP levels (59.4 vs 64.2 pg/ml, consecutively), clinical and
      echocardiographic characteristics. In logistic regression analysis neither
      baseline echocardiographic variable nor ANP level, predicts successful
      cardioversion over a 1-month period of observation. CONCLUSION: Echocardiographic
      data and ANP level should not be included as an important variable when
      considering patients for cardioversion.

PMID- 16098391
TI  - Heart failure due to left ventricular systolic dysfunction: treatment at
      discharge from hospital and at one year.
AB  - BACKGROUND: The treatment of heart failure (HF) due to left ventricular systolic
      dysfunction has been defined in recent guidelines, but these guidelines are not
      always applied in routine clinical practice. One of the objectives of the ETICS
      study was to evaluate medical treatment at discharge and after 1 year in patients
      hospitalised for a first episode of congestive HF due to left ventricular
      systolic dysfunction in 2000. METHODS: One hundred and seventy nine patients (63%
      males, mean age of 69+/-13 years) with an ejection fraction < or = 40% were
      prospectively included. The main aetiology was ischaemic heart disease (44%).
      RESULTS: The drugs prescribed at discharge and at one year, respectively, were
      loop diuretics in 95% and 91% of cases, angiotensin-converting enzyme (ACE)
      inhibitors in 82% and 75%, spironolactone in 35% and 37%, beta-blockers in 25%
      and 41%, digitalis glycosides in 34% and 30% of cases, and nitrates in 20% and
      16% of cases. ACE inhibitors were prescribed at discharge and at 1 year at
      dosages reaching 64+/-29% and 72+/-30% of the recommended doses, respectively,
      and beta-blockers were prescribed at 26+/-16% and 35+/-25% of recommended doses,
      respectively. CONCLUSION: Diuretics and ACE inhibitors are largely prescribed in
      HF due to left ventricular systolic dysfunction, followed by spironolactone. Beta
      blockers are still underused both in terms of the rate of patients receiving them
      and the daily doses. These results highlight the value of continuing to widely
      circulate official practice guidelines in order to improve the management of HF
      due to left ventricular systolic dysfunction.

PMID- 16098392
TI  - Increased long term rates of stent thrombosis and mortality in patients given
      clopidogrel as compared to ticlopidine following coronary stent implantation.
AB  - BACKGROUND: Clopidogrel has largely replaced ticlopidine following coronary stent
      implantation. Recently, concern has been raised regarding the possibility of
      excess long term mortality in patients given clopidogrel rather than ticlopidine
      following coronary stenting. METHODS: We studied 1519 consecutive patients who
      underwent 2020 stent implantations and were discharged on dual antiplatelet
      regimens of either aspirin and ticlopidine or aspirin and clopidogrel given for
      up to 4 weeks. Thrombotic stent occlusion (TSO) was defined as ST elevation
      myocardial infarction in the stented artery territory associated with
      angiographic demonstration of complete stent occlusion. Mortality follow up was
      obtained for all patients by linkage to the Population Register. Follow up
      duration was 12 months. RESULTS: TSO occurred in 37 stents at a median of 29 days
      post procedure. Of these cases, six occurred in the ticlopidine group (0.7%) and
      31 in the clopidogrel group (2.8%) (p<0.01). The median time to TSO was 34 days
      and 28 days in ticlopidine and clopidogrel treated patients, respectively
      (p<0.01). After controlling for multiple demographic, clinical and angiographic
      variables clopidogrel (vs. ticlopidine) treatment remained the sole predictor of
      TSO (OR: 5.4, 95% CI=1.2-24.1, p=0.028). Of even more concern, clopidogrel
      treatment was associated with an increased risk of 1 year mortality (OR: 1.8, 95%
      CI=1.2-2.8). CONCLUSIONS: Long term follow up after stent implantation in
      patients receiving the traditional 2-4 weeks course of dual antiplatelet therapy
      reveals increased rates of TSO and mortality in patients given clopidogrel as
      opposed to ticlopidine. Whether longer treatment with clopidogrel will change
      these observations deserves further study.

PMID- 16098393
TI  - Oxidized LDL inhibit hepatocyte growth factor synthesis in coronary smooth muscle
      cells.
AB  - Hepatocyte growth factor (HGF) is a potent regeneration factor for endothelial
      and epithelial cells, and has also been shown to modulate extracellular matrix
      synthesis and matrix metalloproteinase activity in renal epithelial cells and
      tumor cells. Controversial results have been published concerning the possible
      role of HGF in the pathogenesis of coronary atherosclerosis. In this study, we
      have investigated the effect of oxidized low density lipoproteins (LDL) and
      elevated glucose concentrations on HGF synthesis in cultured human coronary
      artery smooth muscle cells. In addition, we have studied whether HGF modulates
      the release of extracellular matrix, extracellular matrix metalloproteinase
      inducer (EMMPRIN) and matrix metalloproteinases (MMP) by coronary artery smooth
      muscle cells. Oxidized LDL (1-10 microg/ml) induced a significant dose-dependent
      decrease of HGF release and a concomitant decrease of HGF mRNA expression,
      whereas native LDL and elevated glucose concentrations induced no significant
      changes of HGF synthesis. Incubation of cultured human coronary smooth muscle
      cells with human HGF (1-100 ng/ml) did not significantly alter cell migration and
      collagen I, fibronectin, EMMPRIN, MMP-1, MMP-2 and MMP-9 release. In summary, our
      results provide evidence that HGF does not promote coronary plaque growth or
      plaque destabilization. Regarding the fact that HGF is a potent endothelial cell
      regeneration factor, the observed downregulation of HGF synthesis by oxidized LDL
      supports the concept that HGF might be a protective factor in coronary
      atherosclerosis and that a decrease rather than an increase of HGF synthesis
      might promote coronary atherosclerosis.

PMID- 16098394
TI  - Lack of radiological awareness among physicians working in a tertiary-care
      cardiological centre.
AB  - BACKGROUND: Medical irradiation is the most important artificial source of
      exposure to ionising radiations in Europe and implies biorisks. AIM: To assess
      the level of radiological awareness in a tertiary-care referral centre of adult
      pediatric cardiological excellence. METHODS: One hundred physicians (31 women,
      age=41+/-8 years) were polled with a simple, one-page, multiple choice
      questionnaire. Twenty-five physicians worked in a pediatric, 75 in an adult
      cardiology centre. RESULTS: Eighty-nine of the polled physicians wrongly
      estimated the contribution of nuclear and radiological tests in overall radiation
      exposure of average US inhabitant as <0.01% (36% of physicians) or <1% (31%) or
      <10% (22%) (correct answer given by 11% of physicians: >10%). Ninety-five
      physicians wrongly estimated the risk of fatal cancer associated with a stress
      myocardial perfusion scintigraphy procedure as "zero" (48%) or "<1 in 10
      million"(19%) or "<1 in 1 million" (28%) (correct answer given by 5%: >1 in
      10,000 tests). Seventy-one wrongly estimated the dose exposure of a myocardial
      stress perfusion scintigraphy as equal to one (13%), or one-half (9%), or three
      times (49%) that of a chest X-ray (correct answer given by 29%: 500 times). The
      average level of radiological awareness was not correlated to the number of
      radiological-nuclear exams performed/prescribed per year and to the type of
      (adult or pediatric) working environment. CONCLUSION: Physicians working in an
      adult and pediatric cardiological environment of excellence are largely unaware
      of environmental impact, biorisks and dose exposure of the ionising exams they
      prescribe and/or perform daily.

PMID- 16098395
TI  - Usefulness of MRI in the follow-up of patients with repaired aortic coarctation
      and bicuspid aortic valve.
AB  - BACKGROUND: The long-term outcome of repaired aortic coarctation may be
      complicated by dilatation of the ascending aorta notably in patients with
      bicuspid aortic valve. Magnetic resonance imaging was used to compare the size of
      the ascending aorta in patients with bicuspid or tricuspid aortic valve. METHODS:
      In 50 patients with a repair of aortic coarctation, the size of the ascending
      aorta was measured in a bicuspid aortic valve group (n=11) and a tricuspid aortic
      valve group (n=39). The aortic diameter was measured at the level of the sinus of
      Valsalva and at the widest part of the ascending aorta using magnetic resonance
      imaging. RESULTS: The mean age of patients at surgical repair was respectively
      2.2+/-3.3 years for the bicuspid aortic valve group and 2.5+/-3.5 years for the
      tricuspid aortic valve group (p=NS) and the mean age at the time of the magnetic
      resonance imaging was 10.2+/-4.7 years and 9.3+/-5.9 years (p=NS) respectively. A
      significant difference in the aortic diameter was found between the bicuspid
      aortic valve group and the tricuspid aortic group both at the level of sinus of
      Valsalva (34.8+/-8.2 mm, 19.5+/-4.4 mm, respectively, p<0.01) and at the level of
      the ascending aorta (36.8+/-7.2 mm, 16.9+/-3.4 mm, respectively, p<0.01).
      CONCLUSIONS: The occurrence of ascending aortic dilatation is significantly
      associated with the presence of a bicuspid aortic valve. This requires long-term
      follow-up, which can be effectively performed by magnetic resonance imaging.

PMID- 16098396
TI  - Detection and assessment of coronary artery anomalies by three-dimensional
      magnetic resonance coronary angiography.
AB  - BACKGROUND: Coronary artery anomalies (CAAs) are a relatively rare condition
      usually diagnosed in vivo by conventional angiography. In the past few years
      Magnetic resonance coronary angiography (MRCA) has been used to detect CAAs and
      found to be highly accurate. No data is available regarding the ability of MRCA
      to detect previously not suspected anomalies. METHODS: We prospectively analyzed
      the origin and course of 336 patients undergoing a diagnostic Cardiovascular
      magnetic resonance (CMR) study. After the completion of a standard examination a
      navigator-echo 3D-MRCA low-quality scan was used in all the cases to rule out
      CAAs. The high-quality MRCA was applied only if an abnormal coronary arterial
      tree was seen. RESULTS: Nineteen patients with CAAs (12 men, 7 women; mean age,
      53+/-18 years) were identified by MRCA. Six out of the 19 CAAs subjects had
      already been detected by other means (coronary angiography in 5, and
      transesophageal echocardiography in 1 case). However in none of them a complete
      anatomical assessment was achieved. In 13 patients CAAs were an unexpected and
      new finding. MRCA was able to assess the origin and proximal course of the
      anomalous artery in all the cases. CONCLUSIONS: MRCA is able to detect the
      presence and anomalous course of CAAs. Besides offering precise information about
      already suspected CAAs, MRCA can identify anomalies previously not suspected.
      This study suggests a potential role for MRCA as a screening tool for CAAs in
      young patients with angina, ventricular arrhythmias, or unexplained syncope as
      well as in highly competitive athletes.

PMID- 16098397
TI  - Effect of physical training on quality of life and oxygen consumption in patients
      with congestive heart failure.
AB  - AIM: To assess changes in quality of life (QoL) and oxygen consumption produced
      by two different patterns of physical training in patients with congestive heart
      failure (CHF). MATERIAL AND METHODS: 42 men (mean age 55.9+/-8.1 years) with
      ischaemic CHF lasting 3.1+/-1.0 years. Patients were randomised into three groups
      each consisting of 14 men: group A--with constant workload, group B-with
      progressive/increasing workload, each trained up to 6 months and group C--not
      trained. QoL was assessed at baseline and at 6 months by means of the
      Psychological General Well-being Index (PGWB) and the Subjective Symptoms
      Assessment Profile (SSA-P). Cardiopulmonary exercise test and echocardiography
      were performed twice. RESULTS: At 6 months improvement in PGWB total index was
      observed, both in groups A and B (p<0.01). Men from groups A and B reported less
      cardiac symptoms (p<0.01), emotional distress (p<0.01), peripheral circulatory
      symptoms (p<0.01) and dizziness (p<0.01) in SSA-P. Improvement in sexual life was
      observed only in group B (p<0.01). Overall improvement of QoL was greater in
      group B than in group A as well as oxygen uptake (p<0.01). Higher QoL correlated
      positively with peak VO2 only in group B (r=0.56, p<0.05). CONCLUSIONS: Physical
      training improves QoL in men with CHF, but only progressive/increasing workload
      seems to markedly improve oxygen uptake. Improvement of QoL is related to
      psychological well-being and physical complaints associated with CHF.

PMID- 16098398
TI  - Six mechanisms of supraventricular tachycardia in the same patient: report of a
      case.
AB  - An 18-year-old girl had been suffering from palpitations for 3 years. After a
      normal and asymptomatic pregnancy, she became highly symptomatic with more than 6
      tachycardia paroxysms a week, many of them requiring emergency hospitalizations
      because of hemodynamic collapse. The electrophysiological evaluation revealed
      dual A-V nodal pathways and the presence of 4 accessory pathways (3 in the left A
      V ring: lateral, posterior, and posteroseptal, 1 right posteroseptal) with 5
      types of atrioventricular tachycardia and atrial flutter. The 4 accessory
      pathways and the slow A-V nodal pathway were successfully ablated, and the
      patient has been asymptomatic for 12 months without taking antiarrhythmic drugs.

PMID- 16098399
TI  - Coronary vasospasm secondary to hypercholinergic crisis: an iatrogenic cause of
      acute myocardial infarction in myasthenia gravis.
AB  - Patients with myasthenia gravis undergo lifelong treatment with
      anticholinesterase agents. While the heart is usually unaffected by this disease,
      clinicians should bear in mind the potential adverse interaction between cardiac
      function and the underlying myasthenic disease or its specific medications. In
      the present article we report, to the best of our knowledge for the first time in
      the literature, a case of vasospastic acute myocardial infarction due to
      iatrogenic hypercholinergic crisis secondary to anticholinesterase therapy in an
      elderly female with myasthenia gravis. This clinical vignette emphasizes the
      importance of taking into account the potential vasospastic effect of
      anticholinesterase drugs. Indeed, prompt recognition of the pathophysiology of
      myocardial ischemia due to iatrogenic hypercholinergic crisis is pivotal to the
      timely and appropriate management of this medical emergency, as well as
      prevention of future recurrences.

PMID- 16098400
TI  - Chest pain and ST elevation associated with fever in patients with asymptomatic
      Brugada syndrome: fever and chest pain in Brugada syndrome.
AB  - Brugada syndrome is a disease with a high risk of sudden cardiac death. Genetic
      mutations of the cardiac sodium channel are linked to the characteristic
      electrocardiogram abnormality of Brugada syndrome. Dysfunction of the mutated
      sodium channel is reported to be temperature-sensitive. We experienced two
      patients with asymptomatic Brugada syndrome who showed significant ST elevation
      in precordial leads while they were in a febrile state. Moreover, these patients
      had chest pain during precordial ST elevation. From these cases, asymptomatic
      Brugada syndrome should be considered as one of differential diagnoses when we
      examine the patients who complained of fever and chest pain. Furthermore, we
      should lower the elevated body temperature in patients with Brugada syndrome,
      because fever caused spontaneous ST elevation leading to fatal ventricular
      arrhythmias.

PMID- 16098401
TI  - Effect of coronary angioplasty on Helicobacter pylori IgG antibody: lack of
      association between high sensitive C reactive protein and Helicobacter pylori IgG
      antibody levels.

PMID- 16098402
TI  - Using WHO's body mass index cutoff points to classify as overweight and obese
      underestimates the prevalence of overweight and obese among the Chinese.

PMID- 16098403
TI  - Television viewing as a global risk factor for childhood obesity.

PMID- 16098404
TI  - Uncommon electrocardiogram in a patient with right atrial thrombus and pulmonary
      embolism.

PMID- 16098405
TI  - Isolated left ventricular non-compaction in a patient with pre-excited atrial
      fibrillation.

PMID- 16098406
TI  - Adrenal pheochromocytoma associated with dramatic cyclic hemodynamic
      fluctuations.
AB  - A 52-year-old woman with a right adrenal pheochromocytoma had repetitive attacks
      of symptomatic hypotension/shock with systolic blood pressure (SBP)<50 mmHg
      followed by hypertension/hypertensive crises with SBP>300 mmHg. A non-invasive
      recording of beat-to-beat SBP, diastolic blood pressure (DBP), heart rate (HR),
      stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) was
      collected for 346 min. Twenty hemodynamic cycles occurred during this time,
      lasting 17 min on average, with the most dramatic changes of TPR. The ratio of
      the highest to the lowest observed values was nearly 12:1 for TPR, over 6:1 for
      both SBP and DBP, over 4:1 for CO, and nearly 4:1 for SV and 2:1 for HR. The
      fluctuations of TPR preceded changes of all other hemodynamic variables.

PMID- 16098407
TI  - Explicit rationing of elective services: implementing the New Zealand reforms.
AB  - In an attempt to make rationing of elective surgery in the publicly funded health
      system more explicit, New Zealand has developed a booking system for surgery
      using clinical priority assessment criteria (CPAC). This paper is based on
      research undertaken to evaluate the use of CPAC. To explore whether the goals of
      explicit rationing were being met 69 interviews were undertaken with policy
      advisors, administrators and clinicians in six localities throughout New Zealand.
      The aims of reforming policy for access to elective surgery included improving
      equity, providing clarity for patients, and achieving a paradigm shift by
      relating likely benefit from surgery to the available resources. The research
      suggests that there have been changes in the way in which patients access
      elective surgery and that in many ways rationing has become more explicit.
      However, there is also some resistance to the use of CPAC, in part due to
      confusion over whether the tools are decision-aids or protocols, what role the
      tools play in achieving equity and differences between financial thresholds for
      access to surgery and clinical thresholds for benefit from surgery. For many
      surgical specialties implicit rationing will continue to play a major part in
      determining access to surgery unless validated and reliable CPAC tools can be
      developed.

PMID- 16098408
TI  - Why do health and social care providers co-operate?
AB  - Within Europe, although there are numerous examples of poor co-ordination in the
      delivery of integrated care, many providers do co-operate. We wanted to know why
      providers are moved to co-operate. In terms of systematic research, this is a new
      field; researchers have only begun to theorise about the rationales for co
      operation. Practically, the issue of achieving co-operation attracts much
      attention from policymakers. Understanding the reasons for co-operation is a
      prerequisite for developing effective policy in support of integrated care. Our
      aim is to explore the comparative validity of different theoretical perspectives
      on the reasons for co-operation, to indicate directions for further study and for
      policy making. We used data from three successive studies to perform pattern
      matching with six established theoretical perspectives: transaction costs
      economics, strategic choice theory, resource dependence theory, learning theory,
      stakeholder theory and institutional theory. Insights from the studies were
      compared for validating purposes (triangulation). The first study concerned the
      evaluation of the Dutch 'National Home Health Care Programme' according to the
      case study methodology. The second and third studies were surveys among project
      directors: questionnaires were based on the concepts derived from the first
      study. Researchers should combine normative institutional theory, resource
      dependence theory and stakeholder theory into one perspective, in order to study
      relationship formation in health and social care. The concept of institutions
      (rules) is the linchpin between the theories. Policy makers must map the
      institutions of stakeholders and enable integrated care policy to correspond with
      these institutions as much as possible.

PMID- 16098409
TI  - Inequity in the price of physician activity across surgical procedures.
AB  - OBJECTIVES: A rational payment system is being sought in Japanese health care-one
      that accurately reflects the required time and the level of technical difficulty
      when valuing physician activity. The objective of this study is to examine the
      current surgical payment system in Japan by clarifying the hourly values
      allocated to physician activity. METHODS: This study focused on the 22 surgical
      procedures most frequently registered in our study database of administrative
      data gathered from 11 teaching hospitals in Japan. The current fee-for-service
      reimbursement system does not formally define which cost components surgical fees
      cover. It was therefore necessary for us to examine directly each reimbursement
      item to determine which component it represented. Next we examined the current
      system from the following viewpoints: (1) variation in the hourly values
      allocated to physician activity, for an individual surgeon or a surgical team,
      among types of surgery by using the actual data; (2) the association between the
      hourly values and the operation time or the level of technical difficulty.
      RESULTS: The hourly values allocated to physician activity were low (US dollars
      61.0 and 121.5 per surgeon: means of case 1 and case 2 estimations). The hourly
      values varied inequitably among types of surgery (from US dollars -28 to 237 and
      from US dollars 6 to 328: ranges in the case 1 and case 2 estimations). When long
      surgeries were excluded, shorter surgeries tended to have higher hourly values.
      The association between the hourly values and the difficulty level was less clear
      and their variation was large even at the same difficulty level. CONCLUSION: In
      the current payment system, the surgical fee is deemed to include fee for
      physician activity as well as materials, equipment and so on. To develop a
      rational payment system, first, the scope of the surgical fee and that of the
      physician activity fee should be separated and clearly defined. Second, the
      latter should be modeled to reflect the manpower volume and the level of
      technical difficulty needed for each surgical procedure. Third, fees should be
      set by utilizing the cost estimates with empirical data.

PMID- 16098410
TI  - Hepatitis A and B seropositivity among medical students.
AB  - OBJECTIVE: Health science students are commonly exposed to some infectious
      agents, including hepatitis A virus (HAV) and hepatitis B virus (HBV), which may
      cause substantial morbidity and even deaths. The identification of prevalence and
      risk factors is essential for implementing efficacious preventive measures. A
      serological survey was performed among medical students of Adnan Menderes
      University Medical Faculty to determine the prevalence of antibodies against HAV
      and HBV, and, as a secondary objective, to determine risk factors for acquisition
      of these infections. METHODS: Nearly all students were included in the study. All
      participants completed a structured questionnaire that assessed demographic and
      socio-economic characteristics. Anti-HAV IgG, anti-HBc IgG, HbsAg and anti-HBs
      were tested using commercially available Elisa kits. RESULTS: A total of 247
      students, 146 (59.1%) male and 101 (40.9%) female, were included in the study.
      The prevalence of anti-HAV IgG was detected as 64%. Number of siblings and place
      of residence were detected as independent factors affecting the anti-HAV
      seropositivity. The prevalence of anti-HBc IgG was detected as 7.3%. Among the
      students positive for anti-HBc IgG, 5 (2%) students were HBsAg positive and the
      other 13 (5.3%) were anti-HBs positive. HBV infection in household members, risky
      sexual behaviour and vaccination were independent factors affecting the
      prevalence of anti-HBc IgG positivity. CONCLUSIONS: The high susceptibility of
      medical students and their increased risk of clinical HAV and HBV infection
      identify a need for primary prevention through the administration of vaccination
      in this group in western Turkey.

PMID- 16098411
TI  - Comparison of cost accounting methods from different DRG systems and their effect
      on health care quality.
AB  - BACKGROUND: Diagnosis related groups (DRGs) are a well-established provider
      payment system. Because of their imminent potential of cost reduction, they have
      been widely introduced. In addition to cost cutting, several social objectives -
      e.g., improving overall health care quality - feed into the DRG system.
      OBJECTIVES: The WHO compared different provider payment systems with regard to
      the following objectives: prevention of further health problems, providing
      services and solving health problems, and responsiveness to people's legitimate
      expectations. However, no study has been published which takes the impact of
      different cost accounting systems across the DRG systems into account. METHODS:
      We compared the impact of different cost accounting methods within DRG-like
      systems by developing six criteria: integration of patients' health risk into
      pricing practice, incentives for quality improvement and innovation, availability
      of high class evidence based therapy, prohibition of economically founded
      exclusions, reduction of fragmentation incentives, and improvement of patient
      oriented treatment. RESULTS: We set up a first overview of potential and actual
      impacts of the pricing practices within Yale-DRGs, AR-DRGs, G-DRGs, Swiss AP-DRGs
      adoption and Swiss MIPP. It could be demonstrated that DRGs are not only a
      'homogenous' group of similar provider payment systems but quite different by
      fulfilling major health care objectives connected with the used cost accounting
      methods. CONCLUSIONS: If not only the possible cost reduction is used to put in a
      good word for DRG-based provider payment systems, maximum accurateness concerning
      the method of cost accounting should prevail when implementing a new DRG-based
      provider payment system.

PMID- 16098412
TI  - Understanding the structure and practices of research ethics committees through
      research and audit: a study from Mexico.
AB  - This paper reports on a series of studies that were conducted at the Mexican
      Institute of Social Security (IMSS) between 2001 and 2002 to determine the role,
      structure and workings of their local research ethics committees (LRECs). The
      IMSS, unlike other Mexican health institutions, has a formal system of
      committees. Such committees operate under a regulatory system and are charged
      with scrutinising all research proposals in order to ensure their scientific
      validity and to protect the rights and well being of research subjects [Instituto
      Mexicano del Seguro Social. Direccion de Prestaciones Medicas (Mexico). Manual de
      Investigacion Medica en el IMSS: Instituto Mexicano del Seguro Social; 1999]. The
      organisation wanted to know how the committees were functioning and if the work
      of the committees needed to be improved. The problems that were encountered
      included issues with the composition of the committees, the process of project
      assessment, the continuing review process, and a lack of motivation of staff. In
      addition a qualitative study [Valdez-Martinez E, Turnbull B, Garduno-Espinosa J,
      Porter JDH. Descriptive ethics: a qualitative study of local research ethics
      committees in Mexico, Developing World Bioethics, 2005, in press] highlighted the
      focus of the committees on rules, regulations and the law with little
      understanding of the important individual role of members in complementing and
      adding to these structures and perspectives. The paper suggests that, to support
      staff and to protect research subjects, the organizational structure, management
      and decision making process of the IMSS's LRECs ought to be assessed regularly
      through audit cycles. In order to support the further development of the
      committees, the aim of the audit cycles should be focused on education and
      development of the vision, perspectives, values, and working processes of each
      LREC.

PMID- 16098413
TI  - The effect of the market opening on trends in smoking rates in Taiwan.
AB  - OBJECTIVES: To examine smoking rates before and after the opening of the market
      to foreign imports. METHODS: Consumer surveys of Monopoly Bureau, National Health
      Interview Survey and official tobacco consumption, production and import data
      were used to calculate smoking rates, cigarette consumption, and the market share
      of imports. Age-adjusted smoking rates were used to compare trends before and
      after the market opening. RESULTS: The market share of the imports reached half
      in 2001 from 2% before opening. Compared to projected rates, smoking rates in
      2001 for all and younger males, and all and younger females were increased by 12,
      6, 202, and 249%, respectively, over and above the projected trends. The ratio of
      smoking rates between younger and older adults became larger, from 0.62 to 0.74
      in males and from 0.32 to 0.98 in females. Per capita consumption increased after
      the market opening, particularly when large increases in smuggled cigarettes were
      considered. CONCLUSIONS: The finding that the market opening triggered an
      increase in smoking rates is contrary to the assertion by U.S. cigarette
      producers that importation would only make smokers switch brands. Younger adults
      and females were more affected, reflecting their higher sensitivity to the appeal
      from foreign cigarettes. Because of the marketing strategy of imports, more young
      people smoked, at an earlier age. Experience from Taiwan revealed that after the
      initial increase in smoking rates, the opening had galvanized the anti-smoking
      sentiments, legitimized and strengthened tobacco control policies and tempered
      the severity of the adverse impact.

PMID- 16098414
TI  - Can we estimate the 'social' value of a QALY? Four core issues to resolve.
AB  - There is growing interest in estimating the 'societal' willingness to pay (WTP)
      for a quality adjusted life year (QALY) to help public health system decision
      makers determine whether a health care programme should/not be undertaken.
      However, there is a lack of clarity in this debate concerning four core issues:
      (i) is 'social' WTP simply the sum of 'individual' WTP; (ii) will 'individual'
      WTP map directly into 'social' WTP; (iii) is 'personal' income the appropriate
      budget constraint; (iv) should WTP be adjusted for ability to pay? This paper
      outlines the relevance and importance of each of these issues in the hope of
      encouraging a wider debate on the core issues that empirical studies will have to
      explore to discover whether such a value may be obtained.

PMID- 16098415
TI  - Process utility from providing informal care: the benefit of caring.
AB  - Though economics is usually outcome-oriented, it is often argued that processes
      matter as well. Utility is not only derived from outcomes, but also from the way
      this outcome is accomplished. Providing care on a voluntary basis may especially
      be associated with such process utility. In this paper, we discuss the process
      utility from providing informal care. We test the hypothesis that informal
      caregivers derive utility not only from the outcome of informal care, i.e. that
      the patient is adequately cared for, but also from the process of providing
      informal care. We present empirical evidence of process utility on the basis of a
      large sample of Dutch caregivers (n=950). We measure process utility as the
      difference in happiness between the current situation in which the care recipient
      is cared for by the caregiver and the hypothetical situation that someone else
      takes over the care tasks, all other things equal. Other background
      characteristics on patient and caregiver characteristics, objective and
      subjective caregiver burden and quality of life are also presented and related to
      process utility. Our results show that process utility exists and is substantial
      and therefore important in the context of informal care. Almost half of the
      caregivers (48.2%) derive positive utility from informal care and on average
      happiness would decline if informal care tasks were handed over to someone else.
      Multivariate regression analysis shows that process utility especially relates to
      caregiver characteristics (age, gender, general happiness, relation to patient
      and difficulties in performing daily activities) and subjective caregiver burden,
      whereas it also depends on the number of hours of care provided (objective
      burden). These results strengthen the idea of supporting the use of informal
      care, but also that of keeping a close eye on the position of carers.

PMID- 16098416
TI  - Gender role and child health care utilization in Nepal.
AB  - OBJECTIVE: To study the gender role in child health care utilization in Nepal.
      METHODS: We analysed 8112 individual observations of age </=15 years from 2847
      households in 274 communities, obtained from the 1996 Nepal Living Standard
      Survey. Four steps of a health seeking action, namely illness reporting, choosing
      an external care, choosing a specific health care provider, and spending money to
      treat the sick child, were examined using discrete/continuous choice models.
      RESULTS: There was no statistically significant difference between boys and girls
      by demographic, socio-economic and geographical status in the sample. However,
      gender was associated with all four utilization decision steps. While the net
      effect of being a boy was modest in illness reporting (p<0.10), it appeared
      stronger in the choice of external care, in the choice of public provider and in
      the choice of expenditure with the private provider (p<0.05). CONCLUSION: Gender
      role not only affects illness reporting but also affects the decision to choose a
      health care provider and how much to spend on the sick child, i.e. it affects the
      entire steps of a health seeking action.

PMID- 16098417
TI  - Revascularization in severe left ventricular dysfunction: the role of viability
      testing.
AB  - Revascularization is a treatment option for moderate-to-severe ischemic
      cardiomyopathy. Limitations of the current literature, lack of completed
      randomized trials, and higher periprocedural risks create significant uncertainty
      about the optimal treatment strategy. This review focuses on the available
      literature describing the effect of revascularization on outcome and the role of
      noninvasive viability testing. It attempts to identify a subset of patients
      likely to benefit from therapy.

PMID- 16098418
TI  - Five-year outcomes after coronary stenting versus bypass surgery for the
      treatment of multivessel disease: the final analysis of the Arterial
      Revascularization Therapies Study (ARTS) randomized trial.
AB  - OBJECTIVES: The long-term (five-year) comparative results of treatment of
      multivessel coronary artery disease with stenting or coronary artery bypass
      grafting (CABG) is at present unknown. BACKGROUND: The Arterial Revascularization
      Therapies Study (ARTS) was designed to compare CABG and stenting in patients with
      multivessel disease. METHODS: A total of 1,205 patients with the potential for
      equivalent revascularization were randomly assigned to CABG (n = 605) or stent
      implantation (n = 600). The primary clinical end point was freedom from major
      adverse cardiac and cerebrovascular events (MACCE) at one year; MACCE at five
      year follow-up constituted the final secondary end point. RESULTS: At five years,
      there were 48 and 46 deaths in the stent and CABG groups, respectively (8.0% vs.
      7.6%; p = 0.83; relative risk [RR], 1.05; 95% confidence interval [CI], 0.71 to
      1.55). Among 208 diabetic patients, mortality was 13.4% in the stent group and
      8.3% in the CABG group (p = 0.27; RR, 1.61; 95% CI, 0.71 to 3.63). Overall
      freedom from death, stroke, or myocardial infarction was not significantly
      different between groups (18.2% in the stent group vs. 14.9% in the surgical
      group; p = 0.14; RR, 1.22; 95% CI, 0.95 to 1.58). The incidence of repeat
      revascularization was significantly higher in the stent group (30.3%) than in the
      CABG group (8.8%; p < 0.001; RR, 3.46; 95% CI, 2.61 to 4.60). The composite event
      free survival rate was 58.3% in the stent group and 78.2% in the CABG group (p <
      0.0001; RR, 1.91; 95% CI, 1.60 to 2.28). CONCLUSIONS: At five years there was no
      difference in mortality between stenting and surgery for multivessel disease.
      Furthermore, the incidence of stroke or myocardial infarction was not
      significantly different between the two groups. However, overall MACCE was higher
      in the stent group, driven by the increased need for repeat revascularization.

PMID- 16098419
TI  - Five-year follow-up of the Argentine randomized trial of coronary angioplasty
      with stenting versus coronary bypass surgery in patients with multiple vessel
      disease (ERACI II).
AB  - OBJECTIVES: The purpose of the present study is to report the five-year follow-up
      results of the ERACI II trial. BACKGROUND: Immediate and one-year follow-up
      results of the ERACI II study showed a prognosis advantage of percutaneous
      coronary intervention (PCI) with stents over coronary artery bypass grafting
      (CABG). METHODS: A total of 450 patients were randomly assigned to undergo either
      PCI (n = 225); or CABG (n = 225). Only patients with multi-vessel disease were
      enrolled. Clinical follow-up during five years was obtained in 92% of the total
      population after hospital discharge. The primary end point of the study was to
      compare freedom from major adverse cardiovascular events (MACE) at 30 days, 1
      year, 3 years, and 5 years of follow-up. RESULTS: At five years of follow-up,
      patients initially treated with PCI had similar survival and freedom from non
      fatal acute myocardial infarction than those initially treated with CABG (92.8%
      vs. 88.4% and 97.3% vs. 94% respectively, p = 0.16). Freedom from repeat
      revascularization procedures (PCI/CABG) was significantly lower with PCI compared
      with CABG (71.5% vs. 92.4%, p = 0.0002). Freedom from MACE was also significantly
      lower with PCI compared with CABG (65.3% vs. 76.4%; p = 0.013). At five years
      similar numbers of patients randomized to each revascularization procedure were
      asymptomatic or with class I angina. CONCLUSIONS: At five years of follow-up, in
      the ERACI II study, there were no survival benefits from any revascularization
      procedure; however patients initially treated with CABG had better freedom from
      repeat revascularization procedures and from MACE.

PMID- 16098420
TI  - Stenting or surgery: an opportunity to do it right.

PMID- 16098421
TI  - The Frontier stent registry: safety and feasibility of a novel dedicated stent
      for the treatment of bifurcation coronary artery lesions.
AB  - OBJECTIVES: The goal of this study was to evaluate the safety and performance of
      the Multi-Link Frontier coronary bifurcation stent system (Guidant Corp., Santa
      Clara, California), a novel dedicated device designed for permanent side branch
      (SB) access, stent delivery by simultaneous kissing balloon inflation, and
      optimal main branch (MB) and SB ostium scaffolding. BACKGROUND: The treatment of
      coronary bifurcation lesions remains challenging, and various approaches using
      stents have been proposed. METHODS: The primary end point was the 180-day
      incidence of major adverse cardiac events (MACE) per intent-to-treat analysis.
      Secondary end points included device success, 30-day MACE, angiographic
      restenosis, and target lesion revascularization (TLR) rates at 180 days. RESULTS:
      After a learning phase of two cases per center, 105 patients were prospectively
      included in 11 centers. The left anterior descending coronary artery/diagonal
      bifurcation was the target in 80% of cases. The Frontier stent was successfully
      implanted in 96 patients (91%), and procedural success was obtained in 93%. Two
      patients suffered in-hospital myocardial infarction (MI) secondary to SB
      occlusion, and one patient underwent elective coronary artery bypass grafting. At
      30 days and 6 months, the MACE rates were 2.9% and 17.1% (no death, no subacute
      stent thrombosis, Q-wave MI 1.0% and 1.9%, non-Q-wave MI 1.0% and 1.9%, TLR 1.0%
      and 13.3%). The MB in-stent restenosis was 25.3%, in-segment 29.9%. The SB
      restenosis was 29.1%. The overall restenosis rate for any branch was 44.8%.
      CONCLUSIONS: The results of this Frontier registry demonstrate the safety and
      performance of this dedicated stent system for the treatment of bifurcation
      lesions. The device can be successfully implanted in more than 90% of all cases,
      with a high procedural success rate and low 30-day and 6-month MACE rates.

PMID- 16098422
TI  - Bifurcation coronary lesions treated with the "crush" technique: an intravascular
      ultrasound analysis.
AB  - OBJECTIVES: We report intravascular ultrasound (IVUS) findings after crush
      stenting of bifurcation lesions. BACKGROUND: Preliminary results with the crush
      stent technique are encouraging; however, isolated reports suggest that
      restenosis at the side branch (SB) ostium continues to be a problem. METHODS:
      Forty patients with bifurcation lesions underwent crush-stenting with the
      sirolimus-eluting stent. Postintervention IVUS was performed in both branches in
      25 lesions and only the main vessel (MV) in 15 lesions; IVUS analysis included
      five distinct locations: MV proximal stent, crush area, distal stent, SB ostium,
      and SB distal stent. RESULTS: Overall, the MV minimum stent area was larger than
      the SB (6.7 +/- 1.7 mm2 vs. 4.4 +/- 1.4 mm2, p < 0.0001, respectively). When only
      the MV was considered, the minimum stent area was found in the crush area (rather
      than the proximal or MV distal stent) in 56%. When both the MV and the SB were
      considered, the minimum stent area was found at the SB ostium in 68%. The MV
      minimum stent area measured <4 mm2 in 8% of lesions and <5 mm2 in 20%. For the
      SB, a minimum stent area <4 mm2 was found in 44%, and a minimum stent area <5 mm2
      in 76%, typically at the ostium. "Incomplete crushing"--incomplete apposition of
      SB or MV stent struts against the MV wall proximal to the carina--was seen in
      >60% of non-left main lesions. CONCLUSIONS: In the majority of bifurcation
      lesions treated with the crush technique, the smallest minimum stent area
      appeared at the SB ostium. This may contribute to a higher restenosis rate at
      this location.

PMID- 16098423
TI  - Nine-month outcome of patients treated by percutaneous coronary interventions for
      bifurcation lesions in the recent era: a report from the Prevention of Restenosis
      with Tranilast and its Outcomes (PRESTO) trial.
AB  - OBJECTIVES: The aim of this research was to determine the influence of
      bifurcation lesions on the outcome of patients undergoing percutaneous coronary
      intervention (PCI) in the recent era. BACKGROUND: The treatment of bifurcation
      lesions by PCI has been associated with an increased complication rate. Whether
      recent improvements of interventional practice have translated into improved
      outcomes in this patient subgroup is unknown. METHODS: The 11,482 patients
      enrolled in the Prevention of Restenosis with Tranilast and its Outcomes (PRESTO)
      were stratified according to the presence (n = 1,412) or absence (n = 10,068) of
      at least one bifurcation lesion treated by PCI. Baseline characteristics and
      outcome of patients undergoing PCI for bifurcation lesions were compared to those
      of patients treated for nonbifurcation lesions. RESULTS: Patients treated for
      bifurcation lesions were less likely to have prior myocardial infarction (MI),
      prior coronary artery bypass graft surgery, and had a higher proportion of
      current stable angina (p < 0.01 for all comparisons). Bifurcation lesions
      involved more frequently the left anterior descending coronary artery and were
      more complex (angulated, eccentric, ostial, and tortuous) than nonbifurcation
      lesions. Percutaneous coronary intervention of bifurcation lesions was
      characterized by less frequent stent implantation (71% vs. 80%); PCI of
      bifurcation lesions was associated with an increased rate of combined end point
      death/MI/target vessel revascularization (TVR) at nine months (18% vs. 15%, p =
      0.002) because of increased rates of TVR (17% vs. 14%, p < 0.001), whereas death
      (1%) and MI (1%) were not different between groups. CONCLUSIONS: Percutaneous
      coronary intervention of bifurcation lesions is associated with higher TVR at
      follow-up. However, the risk of death, MI, death/MI was similar in patients
      treated for bifurcation or nonbifurcation lesions.

PMID- 16098424
TI  - Clinical and angiographic outcome after implantation of drug-eluting stents in
      bifurcation lesions with the crush stent technique: importance of final kissing
      balloon post-dilation.
AB  - OBJECTIVES: The purpose of this research was to evaluate the long-term outcomes
      after implantation of drug-eluting stents (DES) in bifurcation lesions with the
      "crush" technique. BACKGROUND: The long-term outcome of "crush" stenting
      technique has yet to be determined. METHODS: We identified 181 consecutive
      patients who were treated with DES with the "crush" stent technique from April
      2002 to April 2004. Based on the usage of final kissing balloon post-dilation
      (FKB), the patients were divided into an FKB group (n = 116) and a non-FKB group
      (n = 65). RESULTS: Clinical follow-up at nine months was available in all
      patients, and angiographic follow-up in 80% of patients. Three cases (1.7%) of
      intraprocedural stent thrombosis and five (2.8%) cases of postprocedural stent
      thrombosis occurred. Restenosis rate of the main branch in the entire cohort
      lesions was 11.5%. Restenosis rate of the side branch was lower in the FKB group
      than that in the non-FKB group (11.1% vs. 37.9%, p < 0.001). The target lesion
      revascularization (TLR) rate for all patients was 14.9%. The lack of FKB was a
      predictor for TLR (hazard ratio [HR] 4.17; 95% confidence interval [CI] 1.30 to
      14.3, p = 0.02). Diabetes was also a predictor for TLR (HR 1.79; 95% CI 1.14 to
      2.80, p = 0.01). Premature discontinuation of dual antiplatelet therapy (odds
      ratio [OR] 16.8; 95% CI 1.31 to 159.5, p = 0.03) and age (OR 1.10; 95% CI 1.00 to
      1.21, p = 0.048) was associated with the occurrence of postprocedural stent
      thrombosis. CONCLUSIONS: Compared to the absence of FKB, the "crush" stenting
      technique with FKB appears to be associated with more favorable long-term
      outcomes. When utilizing the "crush" stenting technique, FKB is mandatory.

PMID- 16098425
TI  - Bifurcation intervention: is it crush time yet?

PMID- 16098426
TI  - Relationship between operator volume and adverse outcome in contemporary
      percutaneous coronary intervention practice: an analysis of a quality-controlled
      multicenter percutaneous coronary intervention clinical database.
AB  - OBJECTIVES: The aim of our study was to evaluate the volume-outcome relationship
      in a large, quality-controlled, contemporary percutaneous coronary interventions
      (PCI) database. BACKGROUND: Whether the relationship between physician volume of
      PCI and outcomes still exists in the era of coronary stents is unclear. METHODS:
      Data on 18,504 consecutive PCIs performed by 165 operators in calendar year 2002
      were prospectively collected in a regional consortium. Operators' volume was
      divided into quintiles (1 to 33, 34 to 89, 90 to 139, 140 to 206, and 207 to 582
      procedures/year). The primary end point was a composite of major adverse
      cardiovascular events (MACE) including death, coronary artery bypass grafting,
      stroke or transient ischemic attack, myocardial infarction, and repeat PCI at the
      same site during the index hospital stay. RESULTS: The unadjusted MACE rate was
      significantly higher in quintiles one and two of operator volume when compared
      with quintile five (7.38% and 6.13% vs. 4.15%, p = 0.002 and p = 0.0001,
      respectively). A similar trend was observed for in-hospital death. After
      adjustment for comorbidities, patients treated by low volume operators had a 63%
      increased odds of MACE (adjusted odds ratio [OR] 1.63, 95% confidence interval
      [CI] 1.29 to 2.06, p < 0.0001 for quintile [Q]1; adjusted OR 1.63, 95% CI 1.34 to
      1.90, p < 0.0001 for Q2 vs. Q5), but not of in-hospital death. Overall, high
      volume operators had better outcomes than low volume operators in low-risk and
      high-risk patients. CONCLUSIONS: Although the relationship between operator
      volume and in-hospital mortality is no longer significant, the relationship
      between volume and any adverse outcome is still present. Technological
      advancements have not yet completely offset the influence of procedural volume on
      proficiency of PCIs.

PMID- 16098427
TI  - Physiologic assessment of jailed side branch lesions using fractional flow
      reserve.
AB  - OBJECTIVES: This study was performed to evaluate the feasibility of the
      physiologic assessment of jailed side branches using fractional flow reserve
      (FFR) and to compare the measured FFR with the stenosis severity assessed by
      quantitative coronary angiography (QCA). BACKGROUND: It is not well-known which
      side branches should be treated after stent implantation at main branches and how
      to assess the functional significance of these lesions. METHODS: Ninety-seven
      jailed side branch lesions (vessel size > 2.0 mm, percent stenosis > 50% by
      visual estimation) after stent implantation at main branches were consecutively
      enrolled. The FFR was measured using a pressure wire at 5 mm distal and proximal
      to the ostial lesion of the jailed side branch. RESULTS: The FFR measurement was
      successful in 94 lesions. Mean FFRs were 0.94 +/- 0.04 and 0.85 +/- 0.11 at the
      main branches and jailed side branches, respectively. There was a negative
      correlation between the percent stenosis and FFR (r = -0.41, p < 0.001). However,
      no lesion with < 75% stenosis had FFR < 0.75. Among 73 lesions with > or = 75%
      stenosis, only 20 lesions were functionally significant. CONCLUSIONS: The FFR
      measurement in jailed side branch lesions is both safe and feasible. Quantitative
      coronary angiography is unreliable in the assessment of the functional severity
      of jailed side branch lesions, and measurement of FFR suggests that most of these
      lesions do not have functional significance.

PMID- 16098428
TI  - Matching the evaluation of the clinical efficacy of clopidogrel to platelet
      function tests relevant to the biological properties of the drug.
AB  - OBJECTIVES: This study aimed to explore platelet function tests relevant to the
      biological effects of clopidogrel that could help the clinical monitoring of drug
      efficacy. BACKGROUND: Clopidogrel selectively inhibits the P2Y12 receptor, the
      major role of which is stabilization of aggregation, whereas initiation of
      aggregation depends on activity of both P2Y1 and P2Y12 receptors. METHODS: Tests
      used were peak aggregation (Agg(max)) and late aggregation (Agg(6min)), and
      disaggregation, relating to P2Y1 and P2Y12 activity, respectively; and monoclonal
      antibody binding activated glycoprotein (GP) IIb/IIIa receptors (PAC-1) and P
      selectin, measuring activation and secretion. A first study compared
      hirudin/PPACK (r-hirudin and D-phenylalanyl-prolyl-arginine chloromethyl ketone)
      with citrate as blood anticoagulant (16 patients), and a second control study
      compared the effects of clopidogrel, aspirin, or both (20 normal controls).
      RESULTS: Clopidogrel similarly inhibited adenosine 5'-diphosphate (ADP)-induced
      Agg(max) with either anticoagulant, but significantly more Agg(6min) (75% vs.
      31%), P-selectin (72% vs. 53%), and PAC-1 (62% vs. 24%) in hirudin/PPACK. In the
      control study, it inhibited Agg(max) by 22%, and Agg(6min), P-selectin, and PAC
      1, by 69%, 66%, and 55%, respectively (all p < 0.05). Disaggregation at six min
      reached 62% with clopidogrel, but was virtually absent with placebo and aspirin.
      Non-responsiveness as evaluated by inhibition of Agg(max) in citrate was
      diagnosed in 35% of patients; in half this rate by Agg(6min), P-selectin, and PAC
      1; and in 6% to 12% with the latter tests performed in hirudin/PPACK.
      CONCLUSIONS: The evaluation of clopidogrel responsiveness by platelet function
      tests is largely influenced by the choice of blood preservative and functional
      tests. Measures of aggregation stabilization, and of consequent secretion and
      activation, identified most patients as responders, contrasting with measures of
      peak aggregation, by likely reflecting better the interactions clopidogrel and
      the P2Y12 receptor.

PMID- 16098429
TI  - Clopidogrel linking evaluation of platelet response variability to mechanism of
      action.

PMID- 16098430
TI  - Endothelial vasomotor dysfunction in the brachial artery is associated with late
      in-stent coronary restenosis.
AB  - OBJECTIVES: This study examined whether endothelial dysfunction in the brachial
      artery might be associated with late in-stent restenosis (ISR) after percutaneous
      coronary intervention (PCI). BACKGROUND: Simple and noninvasive identification of
      late ISR might help to select patients who require further angiographic
      evaluation. METHODS: Endothelium-dependent flow-mediated dilation (FMD) of the
      brachial artery was measured before (initial FMD) and at six months (follow-up
      FMD) after PCI in 141 consecutive patients who had elective and successful PCI
      with bare metal stents in de novo lesions of native coronary arteries for
      symptomatic coronary artery disease. Follow-up angiography was performed at six
      months after PCI in all patients. RESULTS: With multivariate logistic regression
      analysis, the impairment (< or = 4.8% dilation from baseline diameter) of FMD at
      follow-up showed the strongest association with late ISR (defined as > 50%
      diameter stenosis, n = 46) independently of other clinical and angiographic
      variables known to be associated with ISR (odds ratio 7.4, 95% confidence
      interval 2.8 to 19.2, p < 0.001), whereas the initial FMD did not have the
      association. The sensitivity of impaired FMD at follow-up (69%) in detecting ISR
      was higher than chest pain during the follow-up period (45%), with comparable
      specificity. The impaired FMD in combination with the chest pain increased the
      sensitivity to 90%. CONCLUSIONS: The impairment of FMD in the brachial artery at
      the time of follow-up was independently and closely associated with late ISR in
      native coronary arteries. The noninvasive assessment of FMD at the time of follow
      up might be useful for identification of late ISR.

PMID- 16098431
TI  - Impaired endothelial function in coronary heart disease patients with depressive
      symptomatology.
AB  - OBJECTIVES: The purpose of this study was to assess whether depressive
      symptomatology was associated with vascular endothelial dysfunction in patients
      with coronary heart disease (CHD). BACKGROUND: In patients with CHD, the presence
      of depression is associated with a two to four times increased risk of mortality,
      but the disease pathways involved are uncertain. Endothelial dysfunction is an
      established risk factor for cardiovascular events in patients with CHD. METHODS:
      Flow-mediated dilation (FMD) of the brachial artery, a measure of endothelial
      function, was assessed in 143 patients (99 men, 44 women), ages 40 to 84 years
      (mean age, 63 +/- 10 years), with documented CHD. RESULTS: Patients with
      significant depressive symptomatology, as indicated by a Beck Depression
      Inventory (BDI) score > or = 10 (n = 47) showed attenuated FMD (p = 0.001)
      compared with patients that were not depressed (BDI < 10; n = 96). The use of
      antidepressant medication was associated with improved FMD (p < 0.05).
      CONCLUSIONS: The increased risk of cardiovascular events in CHD patients with
      elevated symptoms of depression may be mediated, in part, by endothelial
      dysfunction.

PMID- 16098432
TI  - The economic effect of a tertiary hospital-based heart failure program.
AB  - OBJECTIVES: This study was designed to determine the economic effect of a
      tertiary heart failure (HF) program at an academic medical center. BACKGROUND:
      Most hospitals use cross-sectional financial models to analyze the economic
      contribution of clinical programs for a budget period. We estimated the
      incremental value of a tertiary hospital HF program on the basis of the
      longitudinal utilization of a sample of HF patients. METHODS: The primary data
      source was a sample of 82 HF patients referred for cardiac transplant evaluation
      at an academic medical center during calendar years 2000 to 2001. Cumulative
      recurrent rates of utilization, cost, and reimbursement for hospital services
      were computed as functions of time using reliability models. The economic
      contribution of patients transplanted was contrasted with those not transplanted.
      RESULTS: Mean hospitalizations and outpatient encounters per patient at the end
      of the first year of follow-up for those transplanted were 2.1 (95% confidence
      interval [CI] 1.6 to 2.7) and 11.9 (95% CI 9.2 to 15.4), compared with 1.1 (95%
      CI 0.8 to 1.6) and 6.0 (95% CI 4.8 to 7.6), respectively, for those not
      transplanted. Mean revenue and direct cost per patient were 194,470 dollars (95%
      CI 136,683 dollars to 276,689 dollars) and 146,623 dollars (95% CI 96,377 dollars
      to 233,065 dollars), respectively, for transplanted patients and 43,587 dollars
      (95% CI 28,149 dollars to 67,503 dollars) and 33,424 dollars (95% CI 21,584
      dollars to 51,760 dollars), respectively, for non-transplanted patients. The
      point estimates of first-year contribution margins per patient for transplanted
      and non-transplanted patients were 47,847 dollars and 10,163 dollars,
      respectively. CONCLUSIONS: Newly evaluated patients for cardiac transplantation
      at an academic medical center generated substantial incident demands for
      inpatient and outpatient services over a two-year follow-up period. The estimated
      contribution margin associated with these services was positive. Hospitals
      without cardiac transplantation that serve high-acuity HF patients may generate
      favorable long-term contribution margins, on the basis of the results for the non
      transplant group.

PMID- 16098433
TI  - Electrogram characteristics in postinfarction ventricular tachycardia: effect of
      infarct age.
AB  - OBJECTIVES: The purpose of this study was to correlate infarct age with
      characteristics of the endocardial electrograms (EGM) obtained in patients
      undergoing mapping procedures for postinfarction ventricular tachycardia (VT).
      BACKGROUND: Experimental studies have demonstrated that infarct age influences
      EGM duration in the subepicardial left ventricle (LV). The relationship between
      infarct age and endocardial EGM characteristics has not been investigated in
      patients with postinfarction VT. METHODS: In a consecutive series of 23 patients
      with a history of remote infarction (range 1 to 31 years) and VT, endocardial LV
      mapping was performed with an electroanatomical mapping system (CARTO, Biosense
      Webster Inc., Diamond Bar, California) during sinus rhythm. Electrogram
      morphology and width were analyzed and correlated with infarct age. Isthmus sites
      of the VT re-entry circuits were identified by entrainment mapping and related to
      the results of substrate mapping. RESULTS: There was a significant correlation
      between infarct age and width of the bipolar endocardial EGM during baseline
      rhythm in the peri-infarct zone (r = 0.84; p < 0.0001). Increasing infarct age
      was associated with progressive activation delays in the scar and with isolated
      potentials separated by an isoelectric interval, the duration of which also
      correlated with infarct age (r = 0.77; p < 0.001). Among all endocardial sites,
      the VT isthmus sites displayed the most delay and broadest EGMs during sinus
      rhythm. CONCLUSIONS: The presence of broad, fractionated EGMs and isolated
      potentials indicates a healed myocardial infarction; the older the infarction,
      the broader the EGM width. Remodeling over time alters the electrophysiologic
      properties of the peri-infarct tissue.

PMID- 16098434
TI  - "The older the broader": electrogram characteristics help identify the critical
      isthmus during catheter ablation of postinfarct ventricular tachycardia.

PMID- 16098435
TI  - The combined use of ibutilide as an active control with intensive
      electrocardiographic sampling and signal averaging as a sensitive method to
      assess the effects of tadalafil on the human QT interval.
AB  - OBJECTIVES: This study was designed to evaluate effects of tadalafil, a
      phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction
      (ED), on the QT interval. BACKGROUND: Cardiovascular disease is common in men
      with ED. Men with cardiovascular disease and ED may have decreased cardiac
      repolarization reserve. METHODS: Effects of tadalafil (100 mg by mouth),
      ibutilide (0.002 mg/kg intravenously), and placebo on the QT interval in healthy
      men were compared (placebo and tadalafil [n = 90], with a subset [n = 61]
      receiving all treatments; mean age 30 years, range 18 to 53 years).
      Electrocardiographic sampling was done for two days before treatment and on
      treatment days. The QT was corrected for RR interval with five correction
      methods, including an individual correction (QTcI). Plasma concentrations of
      tadalafil were measured to evaluate concentration-QT effect relationships.
      RESULTS: At the time corresponding to maximum plasma concentration of tadalafil,
      the mean difference in the change in QTcI between tadalafil and placebo was 2.8
      ms; tadalafil was equivalent to placebo (a priori, upper limit of 90% confidence
      interval < 10 ms [actual = 4.4 ms]; post hoc, upper limit of 95% confidence
      interval < 5 ms [actual = 4.8]). The active control, ibutilide, significantly
      increased QTcI by 6.9 and 8.9 ms compared with tadalafil and placebo,
      respectively. Similar statistical results were obtained with four additional QT
      correction methods. No subject had a QTcI > or = 450 ms or an increase in QTcI >
      or = 30 ms with any treatment. CONCLUSIONS: Based on the a priori statistical
      test of equivalence, placebo and high-dose tadalafil produced equivalent effects
      on the QT interval. This study reliably discerned 5- to 10-ms changes in
      corrected QT in the ibutilide active control group.

PMID- 16098436
TI  - Making a silk purse out of a sow's ear.

PMID- 16098437
TI  - Prevalence and clinical significance of left atrial remodeling in competitive
      athletes.
AB  - OBJECTIVES: In the present study we assessed the distribution and clinical
      significance of left atrial (LA) size in the context of athlete's heart and the
      differential diagnosis from structural heart disease, as well as the proclivity
      to supraventricular arrhythmias. BACKGROUND: The prevalence, clinical
      significance, and long-term arrhythmic consequences of LA enlargement in
      competitive athletes are unresolved. METHODS: We assessed LA dimension and the
      prevalence of supraventricular tachyarrhythmias in 1,777 competitive athletes
      (71% of whom were males), free of structural cardiovascular disease, that were
      participating in 38 different sports. RESULTS: The LA dimension was 23 to 50 mm
      (mean, 37 +/- 4 mm) in men and 20 to 46 mm (mean, 32 +/- 4 mm) in women and was
      enlarged (i.e., transverse dimension > or = 40 mm) in 347 athletes (20%),
      including 38 (2%) with marked dilation (> or = 45 mm). Of the 1,777 athletes,
      only 14 (0.8%) had documented, symptomatic episodes of either paroxysmal atrial
      fibrillation (n = 5; 0.3%) or supraventricular tachycardia (n = 9; 0.5%), which
      together occurred in a similar proportion in athletes with (0.9%) or without
      (0.8%; p = NS) LA enlargement. Multivariate regression analysis showed LA
      enlargement in athletes was largely explained by left ventricular cavity
      enlargement (R2 = 0.53) and participation in dynamic sports (such as cycling,
      rowing/canoeing) but minimally by body size. CONCLUSIONS: In a large population
      of highly trained athletes, enlarged LA dimension > or = 40 mm was relatively
      common (20%), with the upper limits of 45 mm in women and 50 mm in men
      distinguishing physiologic cardiac remodeling ("athlete's heart") from pathologic
      cardiac conditions. Atrial fibrillation and other supraventricular
      tachyarrhythmias proved to be uncommon (prevalence < 1%) and similar to that in
      the general population, despite the frequency of LA enlargement. Left atrial
      remodeling in competitive athletes may be regarded as a physiologic adaptation to
      exercise conditioning, largely without adverse clinical consequences.

PMID- 16098438
TI  - Effects of long-term bosentan in children with pulmonary arterial hypertension.
AB  - OBJECTIVES: This study investigated the long-term outcome of children with
      pulmonary arterial hypertension (PAH) treated with bosentan therapy, with or
      without concomitant prostanoid therapy. BACKGROUND: Bosentan, an oral endothelin
      ET(A)/ET(B) receptor antagonist, improves hemodynamics and exercise capacity in
      adults with PAH; however, limited data are available on its long-term effects in
      children. METHODS: In this retrospective study, 86 children with PAH (idiopathic,
      associated with congenital heart or connective tissue disease) started bosentan
      with or without concomitant intravenous epoprostenol or subcutaneous treprostinil
      therapy. Hemodynamics, World Health Organization (WHO) functional class, and
      safety data were collected. RESULTS: At the cutoff date, 68 patients (79%) were
      still treated with bosentan, 13 (15%) were discontinued, and 5 (6%) had died.
      Median exposure to bosentan was 14 months. In 90% of the patients (n = 78), WHO
      functional class improved (46%) or was unchanged (44%) with bosentan treatment.
      Mean pulmonary artery pressure and pulmonary vascular resistance decreased (64 +/
      3 mm Hg to 57 +/- 3 mm Hg, p = 0.005 and 20 +/- 2 U x m2 to 15 +/- 2 U x m2, p =
      0.01, respectively; n = 49). Kaplan-Meier survival estimates at one and two years
      were 98% and 91%, respectively. The risk for worsening PAH was lower in patients
      in WHO functional class I/II at bosentan initiation than in patients in WHO class
      III/IV at bosentan initiation. CONCLUSIONS: These data suggest that bosentan, an
      oral endothelin ET(A)/ET(B) receptor antagonist, with or without concomitant
      prostanoid therapy, is safe and efficacious for the treatment of PAH in children.

PMID- 16098439
TI  - Improving the outcome of childhood pulmonary arterial hypertension: the effect of
      bosentan in the setting of a dedicated pulmonary hypertension clinic.

PMID- 16098440
TI  - Plasma tissue factor plus activated peripheral mononuclear cells activate factors
      VII and X in cardiac surgical wounds.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that activated
      monocytes with soluble plasma tissue factor (pTF) activate factors VII and X to
      generate thrombin. BACKGROUND: Despite heparin, thrombin is progressively
      generated during cardiac surgery with cardiopulmonary bypass (CPB), produces
      intravascular fibrin and fibrinolysis, and causes serious thromboembolic and
      nonsurgical bleeding complications. Thrombin is primarily produced in the
      surgical wound, but mechanisms are unclear. METHODS: In 13 patients, interactions
      of mononuclear cells, platelets, pTF, and pTF fractions to activate factors VII
      and X were evaluated in pre-bypass, perfusate, and pericardial wound blood before
      and during CPB. RESULTS: Monocytes are activated in wound, but not in pre-bypass
      or perfusate plasma (monocyte chemotactic protein-1 = 29.5 +/- 2.1 pmoles/l vs.
      2.8 +/- 1.2 pmoles/l and 3.3 +/-1.4 pmoles/l, respectively). Wound pTF is
      substantially elevated compared to other locations (3.64 +/- 0.45 pmoles/l vs.
      0.71 +/- 0.65 pmoles/l and 1.31 +/- 1.4 pmoles/l). Supernatant wound pTF contains
      81.7% of TF antigen; wound microparticle pTF contains 18.3%. Wound monocytes and
      all C5a-stimulated monocytes (but not activated platelets) completely convert
      factor VII to factor VIIa with wound pTF. Activated monocytes more efficiently
      activate factor X with wound supernatant TF/factor VII(VIIa) complex than with
      wound microparticle TF/factor VII(fVIIa). The correlation coefficient (r) between
      wound thrombin generation (F1.2) and wound pTF concentration is 0.944 (p =
      0.0004). CONCLUSIONS: During cardiac surgery with CPB, wound monocytes plus wound
      pTF or wound microparticle-free supernatant pTF preferentially accelerate
      activation of factor VII and factor X. This system represents a novel mechanism
      for thrombin generation via the TF coagulation pathway.

PMID- 16098441
TI  - Thickening of the infarcted wall by collagen injection improves left ventricular
      function in rats: a novel approach to preserve cardiac function after myocardial
      infarction.
AB  - OBJECTIVES: We determined whether collagen implantation could thicken the
      infarcted left ventricular (LV) wall and improve LV function. BACKGROUND: We
      hypothesized that thickening the infarcted wall by using collagen might result in
      some benefits that are similar to what previously had been reported when the
      infarcted wall was thickened with cells. METHODS: Fischer rats with one-week-old
      myocardial infarcts were injected with collagen or saline (100 microl) into the
      scar (n = 12 each group). Six weeks later, LV angiograms, hemodynamics, and
      regional myocardial blood flow were assessed. The hearts were processed for
      measurements of postmortem LV volume and histology. RESULTS: Collagen injection
      significantly increased scar thickness (719 +/- 26 microm) compared with the
      saline-treated group (440 +/- 34 microm, p = 2.6 x 10(-6)). By LV angiography,
      stroke volume was significantly larger in the collagen-treated group (163 +/- 8
      microl) than in the saline-treated group (129 +/- 6 microl, p = 0.005), and LV
      ejection fraction was also greater in the collagen-treated group (48.4 +/- 1.8%)
      than in the saline-treated group (40.7 +/- 1.0%, p = 0.002). Analysis of regional
      wall motion demonstrated paradoxical systolic bulging in 5 of 10 saline-treated
      rats that averaged 20.3 +/- 2.6% of the LV diastolic circumference, but in none
      of the 11 collagen-treated rats (p = 0.012). The LV end-diastolic and end
      systolic volumes were 319 +/- 12 microl and 190 +/- 7 microl in the saline
      treated group, respectively. There was a trend for larger LV end-diastolic
      volumes (343 +/- 23 microl), but smaller end-systolic volumes (180 +/- 16 microl)
      in the collagen-treated group. CONCLUSIONS: This study shows that collagen
      injection thickens an infarct scar and improves LV stroke volume and ejection
      fraction, and prevents paradoxical systolic bulging after myocardial infarction.

PMID- 16098442
TI  - Functional and morphologic imaging of coronary atherosclerosis in living mice
      using high-resolution color Doppler echocardiography and ultrasound
      biomicroscopy.
AB  - OBJECTIVES: This study aimed to establish non-invasive methods of assessing
      coronary artery morphology in normal and atherosclerotic mice in vivo.
      BACKGROUND: Coronary flow velocity reserve (CFVR) has been shown to correlate
      with coronary minimal lumen diameter (MLD) in patients with coronary artery
      stenosis. In mice, there are no existing non-invasive imaging techniques allowing
      quantitative measurement of the coronary artery morphology and function. METHODS:
      Systemic hemodynamic effects of adenosine were studied in seven C57BL/6 mice. In
      17 C57BL/6 mice, CFVR was measured in the mid left coronary artery (LCA) using
      either hypoxia- or adenosine-induced coronary hyperemia. Further, in another 10
      atherosclerotic low-density lipoprotein receptor (LDLR)-/- mice, the hypoxia
      induced CFVR was performed and proximal LCA MLD was measured using ultrasound
      biomicroscopy (UBM). Histologic sections of the LCA were collected. RESULTS: The
      adenosine dose of 160 microg/kg/min induced maximal coronary hyperemia without
      any systemic hemodynamic effects. Adenosine and hypoxia-induced CFVR values
      averaged at 2.0 +/- 0.1 and 1.9 +/- 0.3, respectively, in C57BL/6 mice (p = NS).
      In LDLR-/- mice, CFVR and MLD ranged between 1.4 to 2.9 microm and 190 to 370
      microm, respectively. Histology revealed proximal lumen-narrowing plaques in the
      LCA. Significant correlation was found between hypoxia-induced CFVR and the MLD
      (p < 0.005, R2 = 0.8707). CONCLUSIONS: The CDE and UBM technique can be used to
      measure atherosclerosis-related lumen narrowing of the LCA in living mice. These
      non-invasive techniques may provide us with novel tools for following up disease
      status in mouse coronary arteries in a quantitative manner.

PMID- 16098443
TI  - The department of cardiac/vascular medicine and surgery.

PMID- 16098444
TI  - Risk stratification of patients with classic angina pectoris and no history of
      coronary artery disease by dobutamine stress echocardiography.

PMID- 16098445
TI  - A randomized trial comparing 1 mg of oral vitamin K with no treatment in the
      management of warfarin-associated coagulopathy in patients with mechanical heart
      valves.

PMID- 16098446
TI  - Acute aortic dissection presenting with congestive heart failure: results from
      the International Registry of Acute Aortic Dissection.

PMID- 16098447
TI  - Heritability of left ventricular mass and other morphologic variables in
      Caribbean Hispanic subjects: the Northern Manhattan Family Study.

PMID- 16098448
TI  - Patent foramen ovale/atrial septal defect closure and migraine: searching the
      rationale for the procedure.

PMID- 16098451
TI  - Catheter ablation after mitral replacement.

PMID- 16098452
TI  - Myocardial infarction in the absence of obstructive epicardial coronary disease.

PMID- 16098453
TI  - Lack of prognostic impact of elevated troponin levels in patients without
      coronary artery disease.

PMID- 16098454
TI  - Troponin levels and acute coronary syndrome.

PMID- 16098456
TI  - The role of aromatase inhibitors as adjuvant therapy for early breast cancer in
      postmenopausal women.
AB  - For endocrine therapy of hormone-sensitive advanced breast cancer in
      postmenopausal women, the third-generation aromatase inhibitors, letrozole,
      anastrozole, and exemestane, are effective both as alternatives to tamoxifen in
      first-line treatment and following first-line tamoxifen failure. These three
      agents are currently being evaluated as adjuvant therapy of early breast cancer,
      again relative to the standard, tamoxifen. Three treatment strategies are under
      investigation: replacement of tamoxifen as adjuvant therapy for 5 years (early
      adjuvant therapy); sequencing of tamoxifen before or after an aromatase inhibitor
      during the first 5 years (early sequential adjuvant therapy); or following 5
      years of tamoxifen (extended adjuvant therapy). Results of the first early
      adjuvant trial (Arimidex, Tamoxifen Alone or in Combination [ATAC]) demonstrated
      that anastrozole was significantly more effective than tamoxifen in reducing the
      risk of disease recurrence. Two trials sequencing 2-3 years of an aromatase
      inhibitor after 2-3 years of tamoxifen have also reported results. A large trial
      (International Collaborative Cancer Group [ICCG] trial 96) found switching to
      exemestane to be significantly superior to continuing on tamoxifen in disease
      free survival, and in a small study (Italian Tamoxifen Arimidex [ITA] trial),
      similarly sequencing anastrozole after tamoxifen significantly reduced the hazard
      of recurrence compared with remaining on tamoxifen. Extended adjuvant therapy
      with 5 years of letrozole versus placebo following 5 years of tamoxifen was
      evaluated in the MA.17 trial. Compared with placebo, letrozole resulted in a
      significant improvement in disease-free survival that was irrespective of whether
      patients had lymph node-positive or -negative tumours. Results of these four
      trials emphasise the important role of aromatase inhibitors in the adjuvant
      setting, yet the optimal approach still needs to be defined. A number of trials
      further evaluating the three adjuvant treatment strategies are ongoing.

PMID- 16098457
TI  - Influence of psychological response on breast cancer survival: 10-year follow-up
      of a population-based cohort.
AB  - The possibility that psychological response within a few weeks of a breast cancer
      diagnosis can influence the outcome of the disease is a contentious issue.
      Psychological response, including helplessness/hopelessness, fighting spirit and
      depression was assessed in early-stage breast cancer patients between 1 and 3
      months post-diagnosis, in order to ascertain effect on cancer prognosis. Patients
      were followed up for a period of 10 years in order to clarify the effect of
      psychological response on disease outcome. After 10 years, there is a continuing
      effect of helplessness/hopelessness on disease-free survival (adjusted hazard
      ratio (HR) 1.53, 95% confidence interval (CI) 1.11-2.11) but not of depression
      (adjusted HR for overall survival for 'cases' 2.43, 95% CI 0.97-6.10). Longer
      follow-up also indicates that a high fighting spirit confers no survival
      advantage. The results showed that, in patients who were disease-free at 5 years,
      their baseline helpless/hopeless response still exerted a significant effect on
      disease-free survival beyond 5 (and up to 10) years. The effect is therefore
      maintained for up to 10 years of follow-up. Clinicians may wish to screen for
      helplessness around the time of diagnosis in order to target psychological care
      resources. Further large studies, with similarly prolonged follow-up, are needed
      to replicate this effect and clarify its mechanism of action.

PMID- 16098458
TI  - Outcome of patients with advanced gastro-intestinal stromal tumours crossing over
      to a daily imatinib dose of 800 mg after progression on 400 mg.
AB  - In the EORTC-ISG-AGITG trial 946 patients with advanced gastro-intestinal stromal
      tumours (GIST) were randomised to receive 400 or 800 mg of imatinib daily. An
      increase in progression free survival (PFS) was demonstrated for patients
      randomised to the high-dose arm. Patients randomised to low-dose could cross-over
      to high-dose upon progression. We evaluated the feasibility, safety and efficacy
      of this policy. Of the 241 patients available for follow-up, 133 patients (55%)
      crossed over to high-dose imatinib according to the protocol. Of these patients,
      92% had not had a prior dose reduction. The cumulative incidence of subsequent
      dose reductions after cross-over was 17% after six months with 51% discontinuing
      therapy without requiring a dose reduction. The extent of anaemia and fatigue
      increased significantly after cross-over, whilst neutropenia was less severe than
      during low-dose treatment. Objective responses after cross-over included three
      patients (2%) with a partial response and 36 (27%) with stable disease. The
      median PFS after cross-over was 81 days, although 18.1% of patients were still
      alive and progression free one year after cross-over. We conclude that a cross
      over to high-dose imatinib is feasible and safe in GIST patients who progress on
      low-dose therapy.

PMID- 16098459
TI  - Engaging the vascular component of the tumor response.
AB  - Recent research has shed new light on the critical role of tissue
      microvasculature in regulating the tumor response to radiation and drugs. In this
      issue of Cancer Cell, Moeller et al.(2005) demonstrate that HIF-1 activation
      during the course of fractionated radiotherapy initiates pleiotropic adaptive
      responses in both tumor cells and the microvascular network, radiosensitizing
      tumor cells but concomitantly conferring tumor radioresistance due to protection
      of the microvascular endothelium. HIF-1 thus serves as a legitimate target for
      differential modulation of tissue response to radiation.

PMID- 16098460
TI  - A common pathway for genetic events leading to pheochromocytoma.
AB  - Mutations in VHL, RET, NF1, SDHB, SDHC, and SDHD can give rise to
      pheochromocytoma/paraganglioma. These different genetic lesions may all act by
      decreasing the activity of a 2-oxoglutarate-dependent oxygenase, SM
      20/EglN3/PHD3, resulting in reduced apoptosis of neural crest cells during
      development.

PMID- 16098461
TI  - Metastasis gets site specific.
AB  - Organ-specific homing and colonization of cancer cells are important and
      interesting features of metastasis. Molecular programs that contribute to this
      tropism may be elucidated through gene expression profiling with DNA microarrays.
      Using experimentally derived breast cancer cells that home specifically to bone
      or to lung, several investigators have concluded that distinct alterations in
      gene expression underlie metastasis to these sites. Minn et al. (2005) report a
      set of genes involved in lung-specific metastasis of breast cancer; the authors
      have determined the functional contribution of several genes to the metastatic
      cascade, as well as the relevance of these genes to human disease.

PMID- 16098462
TI  - Oh what a tangled web it weaves: BRCA1 and DNA decatenation.
AB  - BRCA1 has significant roles in DNA repair and cell cycle checkpoint control, and
      is important in the maintenance of genomic stability. Defects in these pathways
      likely underpin the cancer susceptibility of BRCA1 mutation carriers. Now, a new
      function for BRCA1 in DNA decatenation--removing the tangles introduced into
      chromosomes as a consequence of DNA replication--is suggested in a new paper by
      Lou et al. (2005) in Nature Structural and Molecular Biology. Ineffective DNA
      decatenation may lead to chromosome breakage and inappropriate repair, adding to
      the roll call of defects in BRCA1 mutant cells.

PMID- 16098463
TI  - Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity.
AB  - We have previously shown that radiation increases HIF-1 activity in tumors,
      causing significant radioprotection of the tumor vasculature. The impact that HIF
      1 activation has on overall tumor radiosensitivity, however, is unknown. We
      reveal here that HIF-1 plays an important role in determining tumor
      radioresponsiveness through regulating four distinct processes. By promoting ATP
      metabolism, proliferation, and p53 activation, HIF-1 has a radiosensitizing
      effect on tumors. Through stimulating endothelial cell survival, HIF-1 promotes
      tumor radioresistance. As a result, the net effect of HIF-1 blockade on tumor
      radioresponsiveness is highly dependent on treatment sequencing, with "radiation
      first" strategies being significantly more effective than the alternative. These
      data provide a strong rationale for pursuing sequence-specific combinations of
      HIF-1 blockade and conventional therapeutics.

PMID- 16098464
TI  - A conditional feedback loop regulates Ras activity through EphA2.
AB  - The EphA2 receptor tyrosine kinase is frequently overexpressed in many cancers,
      including 40% of breast cancers. Here, we show that EphA2 is a direct
      transcriptional target of the Ras-Raf-MAPK pathway and that ligand-stimulated
      EphA2 attenuates the growth factor-induced activation of Ras. Thus, a negative
      feedback loop is created that regulates Ras activity. Interestingly, the
      expression of EphA2 and ephrin-A1 is mutually exclusive in a panel of 28 breast
      cancer cell lines. We show that the MAPK pathway inhibits ephrin-A1 expression,
      and the ligand expression inhibits EphA2 levels contributing to the receptor
      ligand reciprocal expression pattern in these cell lines. Our results suggest
      that an escape from the negative effects of this interaction may be important in
      the development of cancer.

PMID- 16098465
TI  - Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces
      malignant astrocytoma.
AB  - Malignant astrocytoma, the most prevalent primary brain tumor, is resistant to
      all known therapies and frequently harbors mutations that inactivate p53 and
      activate Ras signaling. We have generated mouse strains that lack p53 and harbor
      a conditional allele of the NF1 tumor suppressor that negatively regulates Ras
      signaling. The mice develop malignant astrocytomas with complete penetrance. The
      majority of tumors display characteristics of glioblastoma multiforme with
      concomitant alteration of signaling pathways previously described in the human
      counterparts of this neoplasm. We find that the sequence of tumor suppressor
      inactivation influences tumorigenicity and that earliest evidence of tumor
      formation localizes to regions of the brain that contain a multipotent stem cell
      population capable of in vivo differentiation into neurons and glia.

PMID- 16098466
TI  - Genetic evidence for a tumor suppressor role of HIF-2alpha.
AB  - The hypoxia-inducible transcription factors HIF-1alpha and HIF-2alpha are
      activated in hypoxic tumor regions. However, their role in tumorigenesis remains
      controversial, as tumor growth promoter and suppressor activities have been
      ascribed to HIF-1alpha, while the role of HIF-2alpha remains largely unknown.
      Here, we show that overexpression of HIF-2alpha in rat glioma tumors enhances
      angiogenesis but reduces growth of these tumors, in part by increasing tumor cell
      apoptosis. Moreover, siRNA knockdown of HIF-2alpha reduced apoptosis in hypoxic
      human malignant glioblastoma cells. Furthermore, inhibition of HIF by
      overexpression of a dominant-negative HIF transgene in glioma cells or HIF-2alpha
      deficiency in teratomas reduced vascularization but accelerated growth of these
      tumor types. These findings urge careful consideration of using HIF inhibitors as
      cancer therapeutic strategies.

PMID- 16098467
TI  - HIF overexpression correlates with biallelic loss of fumarate hydratase in renal
      cancer: novel role of fumarate in regulation of HIF stability.
AB  - Individuals with hemizygous germline fumarate hydratase (FH) mutations are
      predisposed to renal cancer. These tumors predominantly exhibit functional
      inactivation of the remaining wild-type allele, implicating FH inactivation as a
      tumor-promoting event. Hypoxia-inducible factors are expressed in many cancers
      and are increased in clear cell renal carcinomas. Under normoxia, the HIFs are
      labile due to VHL-dependent proteasomal degradation, but stabilization occurs
      under hypoxia due to inactivation of HIF prolyl hydroxylase (HPH), which prevents
      HIF hydroxylation and VHL recognition. We demonstrate that FH inhibition,
      together with elevated intracellular fumarate, coincides with HIF upregulation.
      Further, we show that fumarate acts as a competitive inhibitor of HPH. These data
      delineate a novel fumarate-dependent pathway for regulating HPH activity and HIF
      protein levels.

PMID- 16098468
TI  - Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial
      pheochromocytoma genes: developmental culling and cancer.
AB  - Germline NF1, c-RET, SDH, and VHL mutations cause familial pheochromocytoma.
      Pheochromocytomas derive from sympathetic neuronal precursor cells. Many of these
      cells undergo c-Jun-dependent apoptosis during normal development as NGF becomes
      limiting. NF1 encodes a GAP for the NGF receptor TrkA, and NF1 mutations promote
      survival after NGF withdrawal. We found that pheochromocytoma-associated c-RET
      and VHL mutations lead to increased JunB, which blunts neuronal apoptosis after
      NGF withdrawal. We also found that the prolyl hydroxylase EglN3 acts downstream
      of c-Jun and is specifically required among the three EglN family members for
      apoptosis in this setting. Moreover, EglN3 proapoptotic activity requires SDH
      activity because EglN3 is feedback inhibited by succinate. These studies suggest
      that failure of developmental apoptosis plays a role in pheochromocytoma
      pathogenesis.

PMID- 16098469
TI  - Diffusion-weighted 19F-MRI of lung periphery: Influence of pressure and air-SF6
      composition on apparent diffusion coefficients.
AB  - Lung functional magnetic resonance imaging (MRI) has become a reality using
      different inert hyperpolarized gases, such as 3He and 129Xe, which have provided
      an extraordinary boost in lung imaging and has also attracted interest to other
      chemically inert gaseous contrast agents. In this context, we have recently
      demonstrated the first diffusion-weighted images using thermally polarized
      inhaled sulfur hexafluoride (SF6) in small animals. The aim of this study was to
      evaluate whether or not the diffusion coefficient of this fluorinated gas is
      sensitive to pulmonary structure, gas concentration and air pressure in the
      airways. Diffusion coefficients of SF6 (both pure and in air mixtures) measured
      in vitro at different pressures and 20 degrees C showed an excellent agreement
      with theoretical values. Measurements of diffusion coefficients were also
      performed in vivo and post-mortem on healthy rats, achieving satisfactory signal
      to-noise ratios (SNRs), and SF6 gas was found to be in an almost completely
      restricted diffusion regime in the lung, i.e., the transport by molecular
      diffusion is delayed by collisions with barriers such as the alveolar septa. This
      observed low diffusivity means that this gas will be less sensitive to structural
      changes in the lungs than other magnetic resonance sensitive gas such as 3He,
      particularly at human scale. However, it is still possible that SF6 plays a role
      since it opens a new structural window. Thus, the interest of researchers in
      delimiting the important limiting technical factors that makes this process very
      challenging is obvious. Among them, T2 relaxation is very fast, so gradient
      systems with very fast switching rate and probably large radiofrequency (RF)
      power and high field systems will be needed for hexafluoride to be used in human
      studies.

PMID- 16098470
TI  - Differential approach to the study of integral characteristics in polymer films.
AB  - The differential approach is based on the determination of dimensionless
      differential slope, for instance, of current-voltage characteristics (IVC),
      I=f(V). This slope (alpha) is given by formula alpha=d(lgI)/d(lgV). With such
      definition the ranges of constancy of the alpha(V) dependency correspond to the
      part of IVC characterized by the power behaviour (I approximately V(alpha)). The
      differential slope of alpha(V) dependency gamma=d(lgalpha)/dlgV determines the
      exponent behaviour of curve (I approximately exp(eV(gamma)/kT)). Processing by
      the differential approach of the investigated theoretical or experimental
      characteristics permits us to determine the peculiarity of charge flow
      mechanisms, temperature behaviour of conductivity, etc. The theoretical base and
      some applications of differential approach to the investigation of the current
      voltage, temperature and degradation characteristics of the polyaniline and
      poly(p-phenilenevinilene) based structures have been shown.

PMID- 16098471
TI  - Free radical generation during chemical depolymerization of heparin.
AB  - Low-molecular weight heparins (LMWHs), as compared with unfractionated heparin
      (UFH), present superior bioavailability, much longer plasma half-life, and lower
      incidence of side effects. For these reasons, over the past two decades LMWHs
      have become the drugs of choice for the treatment of deep venous thrombosis,
      pulmonary embolism, arterial thrombosis, and unstable angina. Furthermore, their
      use in acute ischemic stroke is currently under study. LMWHs are obtained by UFH
      depolymerization, which can be performed using various methods, including nitrous
      acid depolymerization, cleavage by beta-elimination of benzyl ester, enzymatic
      depolymerization, and peroxyl radical-dependent depolymerization. This article
      addresses the chemical depolymerization, obtained by free radical attack (mainly
      hydroxyl radical), of heparin. The electron spin resonance (ESR) spectroscopy,
      coupled to the spin trapping technique, was employed to study this reaction. Free
      radical-mediated heparin depolymerization was performed under different chemical
      conditions. The final products of the reactions were purified and classified on
      the basis of their molecular weight and other characteristics. The level of
      heparin fragmentation was different depending on the type of depolymerization
      reaction used. Moreover, the level of reproducibility and the resulting radical
      species were different for every type of reaction performed.

PMID- 16098472
TI  - Characterization of thimet- and neurolysin-like activities in Escherichia coli M
      3 A peptidases and description of a specific substrate.
AB  - M 3 A oligopeptidases from Escherichia coli, with hydrolytic properties similar
      to Zn-dependent mammalian thimet oligopeptidase (EP 24.15) and neurolysin (EP
      24.16), were studied aiming at identification of comparative enzyme and substrate
      specificity, hydrolytic products, and susceptibility to inhibitors. Fluorescent
      peptides, neurotensin (NT) and bradykinin (BK), were used as substrates for
      bacterial lysates. Bacterial enzymes were totally inhibited by o-phenanthrolin,
      JA-2 and partially by Pro-Ile, but not by leupeptin, PMSF, E-64, and Z-Pro
      Prolinal, using internally quenched Abz-GFSPFRQ-EDDnp as substrate. The molecular
      mass of the bacterial oligopeptidase activity (77--78 kDa) was determined by gel
      filtration, and the effect of inhibitors, including captopril, suggested that it
      results from a combination of oligopeptidase A (OpdA) and peptidyl dipeptidase
      Dcp (77.1 and 77.5 kDa, respectively). Recombinant OpdA cloned from the same E.
      coli strain entirely reproduced the primary cleavage of fluorescent peptides, NT
      and BK, by the bacterial lysate. Genes encoding these M 3 A enzymes were those
      recognized in E. coli genome, bearing identity at the amino acid level (25--31%)
      with mammalian Zn-dependent oligopeptidases. We also describe a substrate, Abz
      GFSPFRQ-EDDnp, that differentiates bacterial and mammalian oligopeptidases.

PMID- 16098473
TI  - LPS induces permeability injury in lung microvascular endothelium via AT(1)
      receptor.
AB  - Lipopolysaccharide (LPS) is known to stimulate the circulation and local
      production of angiotensin II (Ang II). To assess whether Ang II plays a role in
      LPS-induced acute lung injury, rats were injected with LPS, the microvascular
      endothelial permeability injury was evaluated by histological changes, increased
      pulmonary wet/dry weight ratio, and pulmonary microvascular protein leak.
      Besides, increased rat pulmonary microvascular endothelial cell monolayer
      permeability coefficient (K(f)) was measured after treatment with LPS and/or Ang
      II, respectively. LPS/Ang II, treatment resulted in a significant increase in
      K(f). Ang II cooperates with LPS to further increase K(f). Hence, LPS increases
      pulmonary microvascular endothelial permeability both in vitro and in vivo. Local
      lung Ang II was increased in response to LPS challenge, and elevated Ang II
      ulteriorly exacerbates LPS-induced endothelium injury. [Sar(1),Ile(8)]Ang II, a
      selective block of Ang II type 1 (AT(1)) receptors, eliminated these changes
      significantly. Our conclusion is that the LPS-induced lung injury may be mediated
      by the AT(1) receptor.

PMID- 16098474
TI  - Structural and functional aspects of thyroid peroxidase.
AB  - Thyroperoxidase (TPO) is the enzyme involved in thyroid hormone synthesis.
      Although many studies have been carried out on TPO since it was first identified
      as being the thyroid microsomal antigen involved in autoimmune thyroid disease,
      previous authors have focused more on the immunological than on the biochemical
      aspects of TPO during the last few years. Here, we review the latest
      contributions in the field of TPO research and provide a large reference list of
      original publications. Given this promising background, scientists and clinicians
      will certainly continue in the future to investigate the mechanisms whereby TPO
      contributes to hormone synthesis and constitutes an important autoantigen
      involved in autoimmune thyroid disease, and the circumstances under which the
      normal physiological function of this enzyme takes on a pathological role.

PMID- 16098475
TI  - Outer shape changes of human masseter with contraction by ultrasound morphometry.
AB  - OBJECTIVE: The multipennate masseter has a complex internal architecture, which
      suggests the contraction is not uniform within the muscle. The heterogeneous
      contraction may cause inequable changes of the muscle's outer shape. This study
      aimed to elucidate the outer shape changes of the whole masseter with clenching
      by multipoint measurement of serial ultrasound images. DESIGN: Serial coronal
      images (perpendicular to the FH plane, 3 mm interval) of the right masseter of
      five healthy men were obtained with a real-time ultrasonograph equipped with a 13
      MHz linear-array transducer. To define the relationship between the transducer
      and cranium, we used a 3D mechanical stage with a face-bow. Registrations were
      made during muscle relaxation and maximal clenching. The distance between the
      lateral and medial outlines of the muscle was measured at intervals of 1mm from
      the origin to insertion in each image as the thickness at the corresponding
      measured point. RESULTS: The thickness of the relaxed and contracted muscle (R
      and C) and its difference (Delta) varied among the measured points. Muscle
      thickness at most measured sites increased with clenching, whereas it decreased
      at several sites, mainly near the origin and insertion. There were positive
      correlations in every subject both between R and C, and between C and Delta. On
      the other hand, the correlation between R and Delta were negative or weak.
      CONCLUSION: Changes of thickness with clenching showed great disparity within the
      masseter, which may result from the complexity of the contraction properties due
      to the multipennate structure and functional heterogeneity.

PMID- 16098476
TI  - Shape relaxations in a fluid supported membrane during hydrolysis by
      phospholipase A(2).
AB  - The behavior of a fluid supported membrane during hydrolysis by phospholipase
      A(2) is for the first time visualized by time-resolved fluorescence imaging.
      After a lag phase, hydrolysis proceeds from the boundary of existing holes and
      via nucleation of new holes. During subsequent hydrolysis, the shape of the
      membrane boundary is determined both by hydrolysis and by shape relaxations due
      to the action of line tension. This is manifested by the appearance of Rayleigh
      instabilities in membrane rims and by an effect analogous to domain coarsening in
      phase transitions in which membrane holes decay when they are within a certain
      distance from larger and expanding holes.

PMID- 16098477
TI  - Anxiety sensitivity taxonicity across gender among youth.
AB  - The present investigation comparatively evaluated the latent class structure and
      parameters of anxiety sensitivity (AS) among female and male youth using the
      Childhood Anxiety Sensitivity Index. Participants were 4462 adolescents (2189
      females) in grades 7-12 (M(age)=15.6 years). Consistent with prediction,
      taxometric analyses indicated the latent structure of AS was taxonic in both
      males and females, demonstrating the taxonic latent structure of AS is similarly
      observed across gender. Also consistent with prediction, the base rate of the AS
      taxon differed between genders -- higher for females (12%) compared to males
      (7%). These findings are discussed in terms of their implications for the study
      of AS and panic vulnerability among youth.

PMID- 16098478
TI  - Bisphosphonates may potentiate radiation effects: a new approach in cancer
      treatment?

PMID- 16098479
TI  - Inductive expression and characterization analysis of Paralichthys olivaceus
      pigment epithelium-derived factor in a virally infected cell line.
AB  - Pigment epithelium-derived factor (PEDF) is acknowledged to be a non-inhibitory
      member of the serine protease inhibitor (serpin) superfamily, with
      antiangiogenesis, and neuroprotective and immunoregulatory function, mainly in
      the tissues of nervous system. Here, A PEDF gene homolog, Paralichthys olivaceus
      PEDF (PoPEDF), was isolated from flounder embryonic cells (FEC) treated with UV
      inactivated Grass carp hemorrhage virus (GCHV) and subsequently identified as a
      differentially expressed gene. The full length of PoPEDF cDNA is 1803bp with an
      open reading frame of 1212bp encoding a 403-amino-acid protein. This deduced
      protein contains an N-terminal signal peptide, a glycosylation site, a consensus
      serpin motif, and a 34-mer and a 44-mer fragment, all of which are very conserved
      in the PEDF family. PoPEDF gene exhibits a conserved exon-intron arrangement with
      8 exons and 7 introns. This conserved evolutionary relationship was further
      confirmed by a phylogenetic analysis, where fish PEDFs and mammalian members
      formed a well-supported clade. Constitutive expression of PoPEDF was widely
      detected in many tissues. In response to UV-inactivated GCHV or poly(I:C), PEDF
      mRNA was upregulated in FEC cells with time. This is the first report on the
      transcriptional induction of PEDF in virally infected cells.

PMID- 16098480
TI  - Expression of P-glycoprotein in L1210 cells is linked with rise in sensitivity to
      Ca2+.
AB  - L1210/VCR cell line (R) was obtained by adaptation of the L1210 mouse leukaemia
      cells (S) to vincristine and showed P-glycoprotein (P-gp) mediated multidrug
      resistance (MDR). R cells were observed to be more sensitive to high external
      calcium as parental S. More pronounced calcium uptake was observed for R cells.
      Moreover, differences in intracellular calcium cell localization between S and R
      cells were found ultrastructurally following a calcium precipitating cytochemical
      method. In S cells, calcium precipitates were found to be localized predominantly
      along the cell surface coat and within mitochondria delineating the cristae. In R
      cells, precipitates were also found inside nuclei, at the border of
      heterochromatin clumps, and scattered within the cytoplasm. High extracellular
      calcium did not influence the P-gp mediated extrusion of calcein/AM as P-gp
      substrate. These results indicate that calcium enters and consequently damages
      the MDR cells to a higher extent than parental cells.

PMID- 16098481
TI  - LuxS/autoinducer-2 quorum sensing molecule regulates transcriptional virulence
      gene expression in Clostridium difficile.
AB  - Toxigenic Clostridium difficile CCUG19126 produces the autoinducer-2 (AI-2)
      quorum sensing molecule that induces bioluminescence in Vibrio harveyi BB170
      reporter strain. AI-2-containing cell-free supernatants from mid-log phase C.
      difficile and Escherichia coli DH5alpha expressing recombinant luxS(cd)
      upregulated the transcript levels of tcdA (7-10-fold), tcdB (4-6-fold), and tcdE
      (2-3-fold) in early-log C. difficile. In contrast, no induction occurred when
      cells were exposed to sterile medium or to cell-free supernatant from E. coli
      DH5alpha. AI-2 did not significantly increase the level of toxin A in early-log
      C. difficile. These results suggest that LuxS(cd)-dependent signaling regulates
      virulence gene expression at the transcriptional level in C. difficile.

PMID- 16098482
TI  - MRP1 mutated in the L0 region transports SN-38 but not leukotriene C4 or
      estradiol-17 (beta-D-glucuronate).
AB  - Multidrug resistance protein 1 (MRP1) is an ATP-binding cassette transporter that
      confers multidrug resistance on tumor cells. Much convincing evidence has
      accumulated that MRP1 transports most substances in a GSH-dependent manner. On
      the other hand, several reports have revealed that MRP1 can transport some
      substrates independently of GSH; however, the importance of GSH-independent
      transport activity is not well established and the mechanistic differences
      between GSH-dependent and -independent transport by MRP1 are unclear. We
      previously demonstrated that the amino acids W261 and K267 in the L0 region of
      MRP1 were important for leukotriene C4 (LTC4) transport activity of MRP1 and for
      GSH-dependent photolabeling of MRP1 with azidophenyl agosterol-A (azidoAG-A). In
      this paper, we further tested the effect of W222L, W223L and R230A mutations in
      MRP1, designated dmL0MRP1, on MRP1 transport activity. SN-38 is an active
      metabolic form of CPT-11 that is one of the most promising anti-cancer drugs.
      Membrane vesicles prepared from cells expressing dmL0MRP1 could transport SN-38,
      but not LTC4 or estradiol-17 (beta-D-glucuronate), and could not be photolabeled
      with azidoAG-A. These data suggested that SN-38 was transported by a different
      mechanism than that of GSH-dependent transport. Understanding the GSH-independent
      transport mechanism of MRP1, and identification of drugs that are transported by
      this mechanism, will be critical for combating MRP1-mediated drug resistance. We
      performed a pairwise comparison of compounds that are transported by MRP1 in a
      GSH-dependent or -independent manner. These data indicated that it may be
      possible to predict compounds that are transported by MRP1 in a GSH-independent
      manner.

PMID- 16098483
TI  - Human organic anion transporter hOAT3 is a potent transporter of cephalosporin
      antibiotics, in comparison with hOAT1.
AB  - We examined the substrate specificity of human organic anion transporter (hOAT) 1
      and hOAT3 for various cephalosporin antibiotics, cephaloridine, cefdinir,
      cefotiam, ceftibuten, cefaclor, ceftizoxime, cefoselis and cefazolin by using
      HEK293 cells stably transfected with hOAT1 or hOAT3 cDNA (HEK-hOAT1, HEK-hOAT3).
      Additionally, we examined the uptake of various compounds by these transfectants.
      The mRNA level of hOAT3 in HEK-hOAT3 was about three-fold that of hOAT1 in HEK
      hOAT1. Functional expression of hOAT1 and hOAT3 was confirmed by the uptake of p
      [14C]aminohippurate and [3H]estrone sulfate, respectively. p-[14C]Aminohippurate,
      [3H]estrone sulfate, [14C]captopril, [3H]methotrexate, [3H]ochratoxin A,
      [3H]leucovorin and [3H]cimetidine were shown to be substrates for hOAT1 and
      hOAT3, and [3H]dehydroepiandrosterone sulfate was shown to be a substrate for
      hOAT3. All cephalosporin anitibiotics tested were shown to inhibit the uptake of
      p-[14C]aminohippurate and [3H]estrone sulfate via hOAT1 and hOAT3, respectively,
      in a dose-dependent manner, and the IC50 values of these antibiotics, except for
      cefaclor, for the hOAT1-mediated uptake of p-[14C]aminohippurate were within four
      fold of those for the hOAT3-mediated uptake of [3H]estrone sulfate. The uptake of
      cephaloridine, cefdinir and cefotiam by HEK-hOAT3 was 35-50-fold greater than
      that by control cells. Moreover, the accumulation of the other cephalolsporin
      antibiotics was significantly greater in HEK-hOAT3 than in control cells. In
      contrast, the uptake of these antibiotics by HEK-hOAT1 was within two-fold of
      that by control cells. In conclusion, hOAT3 plays a more important role than
      hOAT1 in the renal secretion of cephalosporin antibiotics.

PMID- 16098484
TI  - Neural and behavioral plasticity associated with the transition from controlled
      to escalated cocaine use.
AB  - BACKGROUND: Rats given extended access to cocaine develop several symptoms of
      addiction, including a gradual escalation of drug intake, whereas rats given
      limited access do not. We asked here whether extended access to cocaine also
      produces drug-induced sensitization, a form of neurobehavioral plasticity
      implicated in addiction. METHODS: Rats were given limited (1 hour/session) or
      extended access (6 hours/session) to self-administered cocaine. Following a
      period of abstinence, rats were selected at random for assessment of their
      psychomotor response to cocaine or drug-seeking during extinction or for anatomic
      studies. RESULTS: When re-exposed to cocaine, rats allowed extended drug access
      showed greater drug-seeking behavior and were hypersensitive (sensitized) to the
      psychomotor activating effects of cocaine compared with rats given limited
      access. Extended access to cocaine was also associated with a greater increase in
      the density of dendritic spines on neurons specifically in the core of the
      nucleus accumbens (and not in the shell or medial or orbital frontal cortex).
      CONCLUSIONS: The transition from stable to escalated cocaine use, a hallmark of
      addiction, is associated with especially robust behavioral sensitization and
      synaptic reorganization in the core of the nucleus accumbens.

PMID- 16098485
TI  - Modest environmental enrichment: effect on a radial maze validation and well
      being of rats.
AB  - Our 8-arm radial maze test was validated to demonstrate memory deficits in rats
      treated with the muscarinic antagonist scopolamine hydro bromide (SHB, 0.1 mg/kg,
      i.p.). To improve quality of life, we enriched the environment of single housing
      rats. Enrichment procedures were chosen to increase the animals' well being
      without disturbing a lot the results of behavioural tests. It is modest,
      consisting of a plastic tube and corn chips. Enriched environment (EE) and Non
      enriched Environment (NE) animals' performances were compared during the 8-arms
      radial maze validation. Enrichment procedures were chosen to increase the
      animals' well being without disturbing the results of behavioural tests. The
      impact of our enrichment conditions was then evaluated on the general behaviour
      of rats, weight evolution and results of a plus maze anxiety test. Results showed
      a deficit and a delay in learning for SHB-treated animals, and a general time
      dependent learning effect, validating our test. No effect of enrichment on
      negative control animals was observed. For SHB-treated animals, enrichment
      increased performances during learning task and accentuated the deficits in test
      task. Exploratory behaviour of enriched animals seemed to be increased. A general
      amelioration of well being for EE animals was found (stable weight). We conclude
      that our enrichment allows increasing exploratory behaviour not modifying radial
      maze sensitivity using a simple modification of our protocol (limitation to 16
      visits/trial). We decided to generalise this enrichment to all our studies, given
      its simplicity and obtained benefits.

PMID- 16098486
TI  - Mitochondrial ultrastructure and apoptotic protein expression in the vestibular
      nucleus complex following unilateral labyrinthectomy.
AB  - We hypothesized that peripheral vestibular disorders might affect mitochondria in
      the vestibular nucleus complex (VNC). We tested this using unilateral
      labyrinthectomy (UL) as a model for the effects of vestibular damage on the VNC
      and used Western blotting and electron microscopy to analyze mitochondria. In
      rats receiving UL we did not find any changes in mitochondrial ultrastructure in
      the medial vestibular nucleus following UL, and there was no change in the
      expression or activation of the apoptosis effector caspase-3 in the whole VNC
      following UL. However, we did detect a small but statistically significant
      upregulation of the anti-apoptotic protein Bcl-2 in the contralateral VNC at 10 h
      post-UL.

PMID- 16098487
TI  - Presence of monoamine oxidase type B protein but absence of associated enzyme
      activity in neurons within the inferior olive nucleus of the rat.
AB  - A previous study demonstrated that monoamine oxidase type B (MAOB) mRNA is
      located in the inferior olive complex (IO). The purpose of the present study was
      to examine whether neuronal cell bodies within the IO also express MAOB protein
      and whether they exhibit associated MAOB enzyme activity. Using
      immunohistochemistry and enzyme histochemistry, we demonstrated that IO neuronal
      cell bodies were positive for MAOB immunohistochemistry but negative for MAOB
      enzyme histochemistry. These findings indicate that IO neuronal cell bodies
      express MAOB mRNA and produce MAOB protein but curiously do not exhibit MAOB
      enzyme activity, as might be expected. The mechanism responsible for the failure
      of MAOB protein to result in enzymatic activity in IO neuronal cell bodies is
      clearly of significance in terms of functionality but remains to be elucidated.

PMID- 16098488
TI  - Preferential differentiation of neural progenitor cells into the glial lineage
      through gp130 signaling in N-methyl-D-aspartate-treated retinas.
AB  - The purpose of this study was to investigate the differentiation of neural
      progenitor cells (NPCs) following retinal transplantation in N-methyl-D-aspartate
      (NMDA)-treated eyes. NMDA was injected into the vitreous cavity of adult rat
      eyes. NPCs were prepared from telencephalic neuroepithelium of enhanced green
      fluorescence protein (EGFP) transgenic mice on embryonic day 14.5. A cell
      suspension was injected into the vitreous cavity in experimental eyes.
      Immunohistochemistry was conducted at 1, 2 or 4 weeks after transplantation of
      NPCs in an effort to determine the survival and differentiation of transplanted
      NPCs. Similar experiments were conducted using glycoprotein (gp)130-null (-/-)
      mice. Examination of retinal sections revealed that transplanted NPCs could
      survive for at least 4 weeks in NMDA-treated retinas. Immunohistochemical studies
      for specific cell-type markers revealed that, among the transplanted NPCs at 2
      weeks after transplantation, the mean percentage (+/-standard deviation) of glial
      fibrillary acidic protein (GFAP)-positive (glial) cells was 63.5 +/- 7.4%,
      demonstrating the differentiation of transplanted NPCs with a preference for the
      glial lineage. Furthermore, the mean percentage of betaIII-tubulin-positive
      (mature neuronal) cells was 18.8 +/- 4.5%. Following transplantation of NPCs
      isolated from gp130-/- mice into NMDA-treated retinas, the mean percentage of
      GFAP-positive cells (17.6 +/- 7.0%), was significantly lower than that in NPCs
      isolated from wild-type mice (59.1 +/- 6.0%, P = 0.04, Mann-Whitney U test).
      Preferential differentiation of NPCs into the glial lineage is induced through
      gp130 signaling in NMDA-treated eyes.

PMID- 16098489
TI  - Effect of 3,4-methylendioxymethamphetamine (MDMA, "ecstasy") on dopamine
      transmission in the nucleus accumbens shell and core.
AB  - It is known that most of drugs abused by humans preferentially stimulate dopamine
      transmission in the shell subdivision of the nucleus accumbens as compared to the
      core. The aim of the present study was to evaluate whether this applies also to
      intravenous 3,4-methylendioxymethamphetamine (MDMA, "ecstasy") administered at
      doses that sustain self-administration behavior in rats. The effect of 0.32,
      0.64, 1.0, 2.0 and 3.2 mg/kg i.v. of MDMA on dopamine transmission in the nucleus
      accumbens shell and core was studied in freely moving rats by means of dual probe
      microdialysis. MDMA dose-dependently stimulated dopamine transmission both in the
      shell and in the core but the increase in the shell was more pronounced compared
      to the core at doses of 0.64, 1.0 and 2.0 mg/kg. The increase of dialysate
      dopamine obtained after 0.32 mg/kg and after 3.2 mg/kg was not significantly
      different in the shell compared to the core of nucleus accumbens. This study
      extends to MDMA the property of other drugs of abuse to increase preferentially
      nucleus accumbens shell dopamine.

PMID- 16098491
TI  - A mild and environmentally friendly scandium(III) trifluoromethanesulfonate
      catalyzed synthesis of bis(3'-indolyl)alkanes and bis(3'-indolyl)-1
      deoxyalditols.
AB  - Bis(3'-indolyl)alkanes and bis(3'-indolyl) derivatives containing a 1
      deoxyalditol moiety were synthesized in the presence of 5 mol% of scandium(III)
      trifluoromethanesulfonate [Sc(OTf)3] in CH3CN or EtOH-H2O mixture as a solvent
      from room temperature to 70 degrees C in good yields (78-97%).

PMID- 16098493
TI  - Effect of saccharide length on the immunogenicity of neoglycoconjugates from
      synthetic fragments of the O-SP of Vibrio cholerae O1, serotype Ogawa.
AB  - A synthetic hexasaccharide, identical to the terminal hexasaccharide of Ogawa
      LPS, coupled to bovine serum albumin induced protective antibodies in mice. To
      determine if there was a minimum saccharide length required for immunogenicity
      and efficacy, shorter (mono- to pentasaccharide) neoglycoconjugates (CHO-BSA)
      were tested in mice. The Ogawa CHO-BSA was inoculated at either a constant mass
      but differing moles, or equal moles but differing masses. Humoral responses were
      essentially the same when mice received 9 microg of the carbohydrate (0.007 mM
      with the pentasaccharide) in each of the neoglycoconjugates prepared from mono-
      through the pentasaccharide, or the same molar amount (0.007 mM), proportionally
      less by weight when going from the penta- to the monosaccharide. These data show
      that, within this dose range, the responses occurred virtually independently of
      the amount of immunogen. Humoral antibodies induced by these immunogens were
      generally not vibriocidal. Selected antisera induced by CHO-BSA immunogens were
      protective, but the ELISA titers of the sera were not predictive of the
      protective capacity. Purified, Ogawa LPS induced anti-Ogawa LPS IgM antibody
      titers similar to those induced by the Ogawa CHO-BSA conjugates. The anti-whole
      LPS sera were strongly vibriocidal, as were the previously reported sera induced
      by hexasaccharide conjugates. This suggests either that the shorter
      oligosaccharides lack a conformational epitope provided by the hexasaccharide or
      that the LPS has additional B cell epitopes or selects different B cells in the
      primary response.

PMID- 16098492
TI  - Preparation of the methyl ester of hyaluronan and its enzymatic degradation.
AB  - A methyl ester of hyaluronan in which the carboxyl groups were fully esterified
      was prepared using trimethylsilyl diazomethane. This derivative, while not
      depolymerized by hyaluronan lyases or hyaluronan hydrolases, was a substrate for
      both chondroitin ACI lyase (EC 4.2.2.5) from Flavobacterium heparinum and
      chondroitin ACII lyase (EC 4.2.2.5) from Arthrobacter aurescens. The major
      product isolated in these depolymerization reactions was methyl alpha-L-threo-hex
      4-enepyranosyluronate-(1-->3)-2-acetamido-2-deoxy-alpha,beta-D-glucopyranoside as
      determined by 1H NMR spectroscopy and MALDITOF mass spectrometry.

PMID- 16098494
TI  - One-pot alpha-glycosylation pathway via the generation in situ of alpha
      glycopyranosyl imidates in N,N-dimethylformamide.
AB  - Divergent pathways are disclosed in the activation of 2-O-benzyl-1-hydroxy sugars
      by a reagent combination of CBr4 and Ph3P, all of which afford one-pot alpha
      glycosylation methods. When this reagent is used in CH2Cl2, the 1-hydroxy sugar
      is converted to the alpha-glycosyl bromide in a conventional way and leads to the
      one-pot alpha-glycosylation method based on a halide ion-catalytic mechanism. In
      either DMF or a mixture of DMF and CHCl3, however, alternative alpha-glycosyl
      species are generated. From the 1H and 13C NMR study of the products, as well as
      the reactions using Vilsmeier reagents [(CH3)2N+=CHX]X- (X=Br and Cl), these were
      identified as cationic alpha-glycopyranosyl imidates having either Br- or Cl-
      counter ion. The cationic alpha-glycosyl imidate (Br-), derived specifically in
      the presence of DMF, is more reactive than the alpha-glycosyl bromide and thus is
      responsible for the accelerated one-pot alpha-glycosylation. The one-pot alpha
      glycosylation methodology performed in DMF was assessed also with different types
      of acceptor substrates including tertiary alcohols and an anomeric mixture of 1
      OH sugars.

PMID- 16098495
TI  - Tolerance induction via a B-cell delivered gene therapy-based protocol:
      optimization and role of the Ig scaffold.
AB  - Our previous studies indicated that antigen-specific tolerance could be achieved
      by the injection of LPS-activated B-cell blasts that were retrovirally gene
      transferred with an IgG-antigen fusion construct. This system was shown to be
      effective for tolerance induction with a variety of inserted antigens ranging in
      size from a single peptide to a large multi-epitope protein in a variety of mouse
      strains. Moreover, it was shown to be effective in four animal models for human
      disease. To optimize the existing protocol, establish the role of the IgG H chain
      scaffold, and provide baseline for potential clinical applications, we examined
      the effects of different B-cell activators, including lipopolysaccharide (LPS),
      anti-CD40, CpG oligodeoxynucleotide (CpG-ODN), and anti-IgM plus IL-4, on B-cell
      proliferation, GFP transduction efficiency, and tolerance induction in vivo. The
      results show that all activators except CpG-ODN have similar effects on
      retroviral gene transfer and peptide-IgG-induced tolerance. Furthermore, dose
      response analyses showed that T-cell tolerance could be induced with 10(5)
      peptide-IgG LPS B-cell blasts, but that 10(6) transduced B-cells were needed for
      humoral unresponsiveness. Transduced anti-IgM-induced blasts were tolerogenic at
      10(6) cells, but no dose of transduced CpG blasts was tolerogenic. Finally, to
      examine the role of IgG scaffold, a retroviral construct encoding lambda
      repressor p1-102 and signal peptide of murine IgG heavy chain was engineered to
      allow secretion of the p1-102 domain in the same manner as that of p1-102-IgG
      fusion protein. The results demonstrate that not only is IgG scaffold important
      in tolerance induction and maintenance of the long-lasting immune
      hyporesponsiveness, but assembly of the IgG heterodimer may be required for the
      efficacy of this system.

PMID- 16098496
TI  - Protective effect of S-adenosylmethionine on cellular and mitochondrial membranes
      of rat hepatocytes against tert-butylhydroperoxide-induced injury in primary
      culture.
AB  - Accumulating evidence that administration of S-adenosylmethionine (SAMe) protects
      hepatocytes against oxidative stress-mediated injury led us to evaluate the
      effect of SAMe on hepatocyte injury induced in culture by oxidant substance tert
      butylhydroperoxide (1.5 mM tBHP) with regard to prevent mitochondrial injury. The
      pretreatment of hepatocyte culture with SAMe in doses of 0.25, 0.5, 1, 2.5, 5,
      10, 25 and 50 mg/l for 30 min prevented the release of LDH from cells incubated
      for 30 min with tBHP in a dose dependent manner. The inhibitory effect of SAMe on
      lipid peroxidation paralleled the effect on cell viability. SAMe also moderated
      the decrease of the mitochondrial membrane potential induced by tBHP. Our results
      indicate that the inhibition of lipid peroxidation by SAMe can contribute to the
      prevention of disruption of both cellular and mitochondrial membranes. While the
      protective effect of SAMe against tBHP-induced GSH depletion was not confirmed,
      probably the most potent effect of SAMe on membranes by phospholipid methylation
      should be verified.

PMID- 16098497
TI  - Metabolic products and pathways of fluorotelomer alcohols in isolated rat
      hepatocytes.
AB  - Fluorotelomer alcohols (FTOHs; CF(3)(CF(2))(x)C(2)H(4)OH; where x=3, 5, 7, 9) are
      a novel class of polyfluorinated contaminants, recently detected in the North
      American atmosphere, that are possible precursors to the series of perfluoroalkyl
      carboxylates (PFCAs) in human blood. An in vivo rat study validated earlier
      independent work that poly- and per-fluoroalkyl carboxylates were metabolites of
      FTOHs, but our detection of several novel metabolites prompted us to examine
      their pathways in greater detail using isolated rat hepatocytes. Using 8:2 FTOH
      (i.e. where x=7) as a model compound, the metabolic products formed by isolated
      rat hepatocytes were identified, and three synthesized intermediates were
      incubated separately to elucidate the metabolic pathways. For 8:2 FTOH, a major
      fate was direct conjugation to form the O-glucuronide and O-sulfate. Using 2,4
      dinitrophenylhydrazine (DNPH) trapping, the immediate oxidation product of 8:2
      FTOH was identified as 8:2 fluorotelomer aldehyde (8:2 FTAL;
      CF(3)(CF(2))(7)CH(2)C(H)O). 8:2 FTAL was transient and eliminated HF non
      enzymatically to yield 8:2 fluorotelomer alpha,beta-unsaturated aldehyde (8:2
      FTUAL; CF(3)(CF(2))(6)CFCHC(H)O) which was also short-lived and reacted GSH and
      perhaps other endogenous nucleophiles. Four polyfluorinated acid intermediates
      were also detected, including 8:2 fluorotelomer carboxylate (8:2 FTCA;
      CF(3)(CF(2))(7)CH(2)C(O)O(-)), 8:2 fluorotelomer alpha,beta-unsaturated
      carboxylate (8:2 FTUCA; CF(3)(CF(2))(6)CFCHC(O)O(-)),
      tetrahydroperfluorodecanoate (CF(3)(CF(2))(6)(CH(2))(2)CO(2)(-)), and
      dihydroperfluorodecenoate (CF(3)(CF(2))(6)CHCHCO(2)(-)). The pathways leading to
      8:2 FTCA and FTUCA involve oxidation of 8:2 FTAL, however, the pathways leading
      to the latter two polyfluorinated acids remain inconclusive. The fate of the
      unsaturated metabolites, 8:2 FTUAL and FTUCA, included conjugation with GSH and
      dehydrofluorination to yield alpha,beta-unsaturated GSH conjugates, and GS-8:2
      FTUAL which was subsequently reduced to the corresponding alcohol.
      Perfluorooctanoate (PFOA) and minor amounts of perfluorononanoate (PFNA) were
      confirmed as metabolites of 8:2 FTOH, and the respective roles of beta- and alpha
      oxidation mechanisms are discussed. The analogous acids, aldehydes, and
      conjugated metabolites of 4:2, 6:2, and 10:2 FTOH (i.e. where x=3, 5, and 9,
      respectively) were also detected, and metabolite profiles among FTOHs generally
      differed only in the length of their perfluoroalkyl chains. Preincubation with
      aminobenzotriazole, but not pyrazole, inhibited the formation of metabolites from
      all FTOHs, suggesting that their oxidation was catalyzed by P450, not alcohol
      dehydrogenase.

PMID- 16098498
TI  - Enhanced oxygen releasing capacity and oxidative stress in diabetes mellitus and
      diabetes mellitus-associated cardiovascular disease: a comparative study.
AB  - BACKGROUND: Macrovascular disease, especially cardiovascular accounts for most of
      the mortality in patients with type 2 diabetes mellitus. We compared oxidative
      stress, thermal stability and oxygen releasing capacity of hemoglobin in patients
      with type 2 diabetes mellitus and diabetes-associated cardiovascular disease.
      METHODS: The study was performed on 38 control subjects, 31 diabetics, 36
      diabetics with cardiovascular complications, and 33 non-diabetic cardiovascular
      subjects. RESULTS: Enhanced oxidative stress was shown by an increased protein
      carbonyl content observed both in plasma and in hemolysate of the diseased
      samples in type 2 diabetes and diabetes-associated cardiovascular diseased
      patients. Altered levels of cytoprotective enzymes were shown by decreased
      catalase activity, increased glutathione reductase activity and unaltered
      superoxide dismutase activity. Peroxidative activity of diseased hemoglobin was
      much higher compared to healthy controls indicating possible structural changes
      in pathologic hemoglobin molecule as a result of disease induced oxidative
      stress. This result is in good agreement with the observation that thermal
      stability of pathologic hemoglobin was also found to be less compared to control
      subjects. Enhanced oxygen releasing capacity of tetrameric oxyhemoglobin was
      monitored in presence of the drug Trifluoperazine in pathologic red blood cells,
      maximum increment being noticed in diabetic cardiovascular diseased subjects.
      CONCLUSION: Hyperglycemia-induced oxidative stress was responsible to affect the
      thermal stability and oxygen releasing capacity of hemoglobin and the effect is
      more pronounced in diabetes-associated cardiovascular disease.

PMID- 16098499
TI  - Thyroid hormone reference intervals in an ambulatory Arab population on the
      Abbott Architect i2000 immunoassay analyzer.
AB  - BACKGROUND: Considerable differences in reference intervals for FT4 and TSH have
      been reported between countries. Method related differences in the distribution
      of free thyroxine (FT4) have also been reported. The aim of this study was to
      establish reference intervals for thyrotrophin (TSH) and FT4 in an ambulatory
      adult (16-75 y) Arab population attending a general practice clinic using the
      Abbott Architect i2000 immunoassay analyzer. METHODS: TSH and FT4 results from
      959 consecutive ambulatory Arab subjects were available. After excluding data
      sets from pregnant women, patients with known and newly diagnosed thyroid
      disease, individuals taking medication that may affect TSH and FT4 and
      individuals with acute illness, 742 data sets were available for analysis. A 2
      way between-groups ANOVA was conducted to explore the impact of age and gender on
      TSH and FT4. RESULTS: TSH showed a non-Gaussian distribution, FT4 showed a near
      normal distribution. There was no significant main effect on FT4 and TSH for age
      and gender. The interaction effect of age and gender also did not reach
      significance. The 95% reference intervals were: TSH 0.30-4.32 mU/l and FT4 9.8
      18.6 pmol/l. The reference intervals for TSH and FT4 determined in this study
      differed from those reported from other countries using the same analytical
      platform and from the 99% reference intervals, provided by the manufacturer.
      CONCLUSIONS: These differences in reference intervals in different populations
      may affect patient management. The data reported reemphasize that each laboratory
      should determine population and method-specific reference intervals.

PMID- 16098500
TI  - Rapid determination of common mutations in glutathione S-transferase gene by PCR
      based methods in healthy Chinese.
AB  - BACKGROUND: The glutathione S-transferase (GST) superfamily comprises multiple
      isozymes with compelling evidence of functional polymorphisms in various ethnic
      groups. All these mutations, in particular those in class mu, pi and theta GST,
      are likely to contribute to interindividual differences in responses to
      xenobiotics including response to chemotherapy and associated with altered
      disease. The frequency of common GST mutations in Uygur Chinese is unknown. We
      investigated the common mutations of GSTM1, GSTT1, and GSTP1 in Uygur (N=154)
      Chinese and compare with Han Chinese (N=196). METHOD: GSTM1 and GSTT1
      polymorphisms were analyzed by multiplexed PCR, and GSTP1 polymorphism was
      detected by PCR-based restriction fragment length polymorphism (RFLP) analysis.
      RESULTS: GSTM1 null genotype was found in 53.2% Uygur Chinese, which was close to
      that in Han Chinese (56.1%) (P=0.592). A significantly lower frequency (P<0.05)
      of GSTT1 null genotype in Uygur Chinese (26.6%) was observed compared with Han
      Chinese (50.0%). Uygur Chinese exhibited a GSTP1 genotype distribution of 51.3%
      I/I, 40.2% I/V and 8.4% V/V, which was different from that in Han Chinese (60.7%
      I/I, 35.2% I/V and 4.1% V/V). CONCLUSIONS: There is marked ethnic difference in
      the frequency of common GSTT1 and GSTP1 mutation, but not GSTM1 mutation, between
      Uygur and Han Chinese.

PMID- 16098501
TI  - Quantification of the carbapenem antibiotic ertapenem in human plasma by a
      validated liquid chromatography-mass spectrometry method.
AB  - BACKGROUND: Ertapenem (Invanz) is a newly developed carbapenem beta-lactam
      antibiotic. LC-MS is the method of choice for therapeutic drug monitoring (TDM)
      of a variety of drugs including antibiotics. No validated LC-MS method for
      ertapenem quantification is described in the literature so far. METHODS: A rapid
      and robust LC-MS quantification method for ertapenem was developed and validated
      for clinical routine application in plasma samples. After immediate stabilisation
      with MES buffer (pH 6.5), samples were prepared for LC-MS analysis using simple
      protein precipitation. LC-MS coupling was realised by the use of a Phenomenex
      Synergi 4micro Polar-RP A80 Mercury LC column (10 x 2.0 mm) in combination with a
      Single-MS (Agilent 1100 LC-MSD SL) operating in negative selected ion monitoring
      (SIM) detection mode with ceftazidime as internal standard for adequate selective
      and sensitive analysis. RESULTS: LC-MS method validation by means of
      determination of limit of detection (LOD 0.1 microg mL-1), lower limit of
      quantification (LLOQ 1 microg mL-1), linearity (0.1-50 microg mL-1), recovery (>
      90%), intra- and inter-day precision (RSD < 10%), accuracy (> 90%), inter-subject
      variability (< 10% at LLOQ), drug stability in plasma (> 3 months) and in post
      extracted samples (> 99% for 24 h), and matrix effects (process efficiency > 90%)
      showed excellent performance parameters considering Guidance for Industry -
      Bioanalytical Method Validation. CONCLUSION: This method is perfectly appropriate
      for routine quantification of ertapenem and possibly other polar carbapenem beta
      lactam antibiotics.

PMID- 16098502
TI  - Development and validation of a simple and direct ELISA method for the
      determination of conjugated (glucuronide) and non-conjugated testosterone
      excretion in urine.
AB  - BACKGROUND: Several methods are now available to estimate urinary testosterone
      levels that can only be performed in established big laboratories using GC/MS
      techniques. In clinical practice or for research projects, an inexpensive method
      that does not require skilled technicians would be useful. A simple, rapid and
      accurate ELISA method has been developed and applied in our laboratory to measure
      urinary non-conjugated and total testosterone. METHODS: High affinity anti
      testosterone antibody and HRP-Donkey anti-sheep IgG (Horse Radish Peroxidase) as
      enzyme tracer were used to develop the ELISA method. The assay was evaluated for
      specificity, sensitivity, parallelism, accuracy and imprecision by the
      established methods on samples obtained from healthy volunteers. The results from
      the direct ELISA were compared to those after enzyme hydrolysis plus solvent
      extraction and HPLC or commercial kits. RESULTS: A satisfactory standard curve
      for the direct testosterone ELISA has been developed with good sensitivity. Cross
      reactivity values of anti-testosterone antibody with major interfering steroids
      were minimal except for testosterone-3-glucuronide (58.8%). The validity of
      urinary testosterone assay was confirmed by the good correlation between the
      results obtained by the direct ELISA and those after enzyme hydrolysis and
      solvent extraction (Y = 0.987X + 0.398, R2 = 0.97). Accuracy studies, parallelism
      and imprecision data were determined and all found to be satisfactory. Urinary
      testosterone excretion values obtained by our direct ELISA from healthy
      volunteers were generally in agreement with those published by other workers.
      Male urinary total testosterone excretion (non-conjugated and testosterone
      glucuronide) ranged from 177.9 to 865.3 nmol/day, which was about 3-6 times more
      than the range for women urinary testosterone excretion (34.5-308.8 nmol/day).
      CONCLUSION: A direct, reliable, easy to perform, sensitive and highly specific
      ELISA type assay for the measurement of total testosterone in urine samples
      (conjugated and non-conjugated) has been developed. The novel features of the
      assay are that it does not require an initial extraction step or involve time
      consuming procedures such as chromatography. A simple method has also been
      developed to measure non-conjugated urinary testosterone excretion after solvent
      extraction alone.

PMID- 16098504
TI  - Antiarrhythmic effect of caffeic acid phenethyl ester (CAPE) on myocardial
      ischemia/reperfusion injury in rats.
AB  - OBJECTIVES: The present study was designed to determine the antiarrhythmic effect
      of caffeic acid phenethyl ester (CAPE), an active component of propolis, which
      exhibits antioxidant properties, in rats subjected to myocardial ischemia and
      ischemia-reperfusion (I/R) injury. DESIGN AND METHODS: Rats were subjected to 30
      min coronary artery occlusion for evaluating the effect of CAPE on the myocardial
      ischemia injury. While in the myocardial I/R injury study, the coronary artery
      was ligated for a 5-min period of ischemia followed by a 30-min period of
      reperfusion. Animals were pretreated with or without CAPE before coronary artery
      ligation and the severity of myocardial ischemia- and I/R-induced arrhythmias and
      mortality were compared. RESULTS: Pretreatment of CAPE (0.1 and 1 microg/kg) not
      only reduced both the incidence and duration of ventricular tachycardia (VT) and
      ventricular fibrillation (VF) but also decreased the mortality during the
      myocardial ischemia and I/R injury period. CONCLUSIONS: Our results suggest that
      CAPE is a potent antiarrhythmic agent with cardioprotective effects in myocardial
      ischemia and I/R injury rats.

PMID- 16098503
TI  - Platelet release of beta-thromboglobulin and platelet factor 4 and serotonin in
      plasma samples.
AB  - OBJECTIVES: Platelet release of alpha granule-derived CXC chemokines and dense
      granule-derived serotonin in plasma samples was evaluated. METHODS:
      Concentrations of the CXC chemokines beta-TG and PF4 were assayed by an enzyme
      immunoassay; serotonin was measured by an HPLC method. RESULTS: Beta-TG and PF4
      were more easily released than serotonin by in vitro procedures. Use of the anti
      platelet cocktail CTAD and preservation of the samples at 4 degrees C were
      necessary to accurately measure beta-TG and PF4, but not serotonin. CONCLUSIONS:
      Assaying serotonin may be useful for assessing platelet activation in vivo as a
      laboratory test because of facile preparation of plasma samples.

PMID- 16098505
TI  - Entrainment of the natural pacemakers of the heart precedes atrial fibrillation.
AB  - A new measure of heart rate variability is proposed to investigate the
      interaction of the sino-atrial (SA) and atrio-ventricular (AV) pacemakers. Using
      electrocardiogram (ECG) fiduciary markers corresponding to the depolarization
      time of the SA and AV pacemakers, the variability of SA and AV depolarization
      rate is jointly analyzed by spectral analysis. The result of this joint analysis
      provides evidence of a distinct pattern of interaction between the SA and AV
      nodes prior to the onset of paroxysmal atrial fibrillation (PAF): frequency
      entrainment between the primary and secondary pacemakers of the heart, occurring
      at the respiratory frequency. We propose a measure of this entrainment as a
      diagnostic indicator for PAF, and compare it to standard diagnostic measures. The
      entrainment measure is found to have greater diagnostic power than five other
      common ECG-derived measures.

PMID- 16098506
TI  - Purification and characterisation of an antifreeze protein from Forsythia
      suspensa (L.).
AB  - Recrystallisation inhibition (RI) activity has been isolated from cold-acclimated
      Forsythia suspensa bark and leaves, which is stable when boiled, and not
      sensitive to reducing agents. The antifreeze activity has been purified to a
      single 20 kDa protein, using anion exchange, hydroxyapatite chromatography, and
      gel filtration. The protein is abundant in forsythia bark with 0.5microg pure
      protein obtained from 35 g bark. RI activity is seen with as little as 6 microg
      ml(-1) protein. Sequence homology was seen with dehydrins, and forsythia AFP
      contains the Y-segment, a conserved region found in many dehydrins.

PMID- 16098507
TI  - Effects of alpha4beta2 and alpha7 nicotinic acetylcholine receptor antagonists on
      place aversion induced by naloxone in single-dose morphine-treated rats.
AB  - Acute dependence can be observed when naloxone is administered 24 h after even a
      single dose of morphine, and nicotine attenuates this naloxone-precipitated
      withdrawal syndrome. This acute dependence has been hypothesized to be associated
      with a dopaminergic mechanism. In the present study, the role of nicotinic
      acetylcholine receptor subtypes in the place aversion induced by naloxone in
      single-dose morphine-treated rats was investigated. Methyllycaconitine (1, 2 and
      5 mg/kg), an alpha7 nicotinic acetylcholine receptor subtype inhibitor,
      significantly and dose dependently inhibited the attenuating effect of nicotine
      on naloxone-induced place aversion. In contrast, dihydroxy-beta-erithroidine (1,
      2 and 5 mg/kg), an alpha4beta2 nicotinic acetylcholine receptor subtype
      inhibitor, did not have any effect on the attenuating effect of nicotine on
      naloxone-induced place aversion. These findings suggested that the alpha7
      nicotinic acetylcholine receptor subtype is associated with the place aversion
      induced by naloxone in single-dose morphine-treated rats. Nicotinic acetylcholine
      receptor subtype inhibitors warrant further study as possible treatment for acute
      dependence.

PMID- 16098508
TI  - Microarray analysis of gene expression in the liver during the urinary ethanol
      cycle in rats fed ethanol intragastrically at a constant rate.
AB  - The regulation of gene expression in the liver of ethanol fed rats was studied
      using microarray analysis. The changes in gene expression were compared between
      pair-fed controls and rats fed ethanol intragastrically at a constant rate for 1
      month. The rats fed ethanol were sacrificed at low and high urinary ethanol
      levels (UAL) during the UAL cycle in order to compare the effects of high and low
      blood alcohol levels (BAL). The results of the microarray analysis indicated that
      the pattern of gene expression was very different when the controls, high UAL,
      and low UAL livers were compared. Many of the gene expression changes reflected
      nonparenchymal cell alterations such as neuroendocrine or muscle related gene
      expression. When the results of protein levels and gene expression were compared
      for individual genes, correlations were variable indicating that post
      translational factors modified the effects of the changes in gene expression.
      This was further emphasized by the fact that activation of proteins by
      phosphorylation as the result of signaling kinase cascades, was not reflected in
      the microarray analysis results. For instance, the importance of blood alcohol
      levels at the time that the assays were performed, profoundly changed the gene
      expression, protein level, and protein phosphorylation level profiles.

PMID- 16098509
TI  - Behavior of tight-junction, adherens-junction and cell polarity proteins during
      HNF-4alpha-induced epithelial polarization.
AB  - We previously reported that expression of tight-junction molecules occludin,
      claudin-6 and claudin-7, as well as establishment of epithelial polarity, was
      triggered in mouse F9 cells expressing hepatocyte nuclear factor (HNF)-4alpha [H.
      Chiba, T. Gotoh, T. Kojima, S. Satohisa, K. Kikuchi, M. Osanai, N. Sawada.
      Hepatocyte nuclear factor (HNF)-4alpha triggers formation of functional tight
      junctions and establishment of polarized epithelial morphology in F9 embryonal
      carcinoma cells, Exp. Cell Res. 286 (2003) 288-297]. Using these cells, we
      examined in the present study behavior of tight-junction, adherens-junction and
      cell polarity proteins and elucidated the molecular mechanism behind HNF-4alpha
      initiated junction formation and epithelial polarization. We herein show that not
      only ZO-1 and ZO-2, but also ZO-3, junctional adhesion molecule (JAM)-B, JAM-C
      and cell polarity proteins PAR-3, PAR-6 and atypical protein kinase C (aPKC)
      accumulate at primordial adherens junctions in undifferentiated F9 cells. In
      contrast, CRB3, Pals1 and PATJ appeared to exhibit distinct subcellular
      localization in immature cells. Induced expression of HNF-4alpha led to
      translocation of these tight-junction and cell polarity proteins to beltlike
      tight junctions, where occludin, claudin-6 and claudin-7 were assembled, in
      differentiated cells. Interestingly, PAR-6, aPKC, CRB3 and Pals1, but not PAR-3
      or PATJ, were also concentrated on the apical membranes in differentiated cells.
      These findings indicate that HNF-4alpha provokes not only expression of tight
      junction adhesion molecules, but also modulation of subcellular distribution of
      junction and cell polarity proteins, resulting in junction formation and
      epithelial polarization.

PMID- 16098510
TI  - Cell-cycle regulators are involved in transient cerebral ischemia induced
      neuronal apoptosis in female rats.
AB  - Recent evidence indicates that cell-cycle regulating proteins are involved in
      apoptotic process in post-mitotic neurons. In this study, we examined cell-cycle
      regulators for G1/S cell-cycle progression after a transient focal cerebral
      ischemia induced by middle cerebral artery (MCA) occlusion. In the cerebral
      frontoparietal cortex, we observed a marked induction of Cyclin D1 (a coactivator
      of Cdks), and proliferating cell nuclear antigen (PCNA), together with
      upregulated Cdk kinase activities. This process is accompanied with multiple
      phosphorylation of retinoblastoma (Rb) protein at Cdk phosphorylation sites in
      neurons from the ischemic cortex. We further examined DNA synthesis by the
      incorporation of BrdU, a nucleotide analog that incorporates into newly
      synthesized DNA. Within 24-h of reperfusion after 60-min occlusion, substantial
      BrdU-positive neurons were observed in the ischemic cortex. Inhibition of Cdk4
      activity during this ischemia/reperfusion is highly neuroprotective. These
      results suggest that ischemia/reperfusion cerebral damage induces signalings at
      the G1/S cell-cycle transition, and may constitute a critical step in the
      neuronal apoptotic pathway in ischemia/reperfusion induced neuronal damage.

PMID- 16098511
TI  - Impairment of the activity of the xenobiotic-metabolizing enzymes arylamine N
      acetyltransferases 1 and 2 (NAT1/NAT2) by peroxynitrite in mouse skeletal muscle
      cells.
AB  - Reactive nitrogen species and their by-products, such as peroxynitrite, modulate
      many physiological functions of skeletal muscle. Peroxynitrite generation
      occuring under specific conditions, such as inflammation, may also lead to
      skeletal muscle dysfunction and pathologies. Arylamine N-acetyltransferases
      (NATs) are xenobiotic-metabolizing enzymes (XMEs) involved in the detoxification
      and/or metabolic activation of several drugs and chemicals. In addition to other
      XMEs, such as gluthatione S-transferases or cytochromes P450, NAT enzymes are
      expressed in skeletal muscle. We show here that functional NAT1 and NAT2 isoforms
      are expressed in mouse myotubes and that peroxynitrite may impair their activity
      in these cells. We show that this inactivation is likely due to the irreversible
      modification of NATs catalytic cysteine residue in vivo. Our results suggest that
      peroxynitrite-dependent inactivation of muscle XMEs such as NATs may contribute
      to muscle dysfunction by impairing the biotransformation activity of this key
      cellular defense enzyme system.

PMID- 16098512
TI  - Conformation-driven and semiquinone-gated proton-pump mechanism in the NADH
      ubiquinone oxidoreductase (complex I).
AB  - A novel mechanism for proton/electron transfer is proposed for NADH-quinone
      oxidoreductase (complex I) based on the following findings: (1) EPR signals of
      the protein-bound fast-relaxing semiquinone anion radicals (abbreviated as Q(Nf)
      ) are observable only in the presence of proton-transmembrane electrochemical
      potential; (2) Iron-sulfur cluster N2 and Q(Nf)- are directly spin-coupled; and
      (3) The projection of the interspin vector extends only 5A along the membrane
      normal [Yano, T., Dunham, W.R. and Ohnishi, T. (2005) Biochemistry, 44, 1744
      1754]. We propose that the proton pump is operated by redox-driven conformational
      changes of the quinone binding protein. In the input state, semiquinone is
      reduced to quinol, acquiring two protons from the N (matrix) side of the
      mitochondrial inner membrane and an electron from the low potential (NADH) side
      of the respiratory chain. A conformational change brings the protons into
      position for release at the P (inter-membrane space) side of the membrane via a
      proton-well. Concomitantly, an electron is donated to the quinone pool at the
      high potential side of the coupling site. The system then returns to the original
      state to repeat the cycle. This hypothesis provides a useful frame work for
      further investigation of the mechanism of proton translocation in complex I.

PMID- 16098513
TI  - Suppression of hypothalamic deiodinase type II activity blunts TRH mRNA decline
      during fasting.
AB  - Fasting is characterized by disrupted thyroid feedback, with suppressed levels of
      thyroid hormones and paraventricular thyrotropin releasing hormone (TRH). We
      found that third ventricle administration of the deiodinase inhibitor, iopanoic
      acid, dose-dependently reduced deiodinase type II (DII) activity selectively in
      the hypothalamus. This suppression of DII by iopanoic acid during fasting
      prevented elevated DII activity and blunted the decline in hypothalamic TRH mRNA
      levels. Because fasting-induced elevation in hypothalamic DII activity is
      paralleled by increased hypothalamic T3 concentration, our study suggests that T3
      formation by DII in the hypothalamus is the cause of disrupted thyroid feedback
      during fasting.

PMID- 16098514
TI  - Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1.
AB  - The small G protein Rheb (Ras homologue enriched in brain) is known to promote
      mammalian target of rapamycin (mTOR) signaling. In this study, we show that Rheb
      like-1 protein (RhebL1) rescues mTOR signaling during nutrient withdrawal and
      that tuberous sclerosis complex-1 (TSC) and TSC2 impairs RhebL1-mediated
      signaling through mTOR. We identify critical residues within the switch I region
      (N41) and 'constitutive' effector (Ec) region (Y/F54 and L56) of Rheb and RhebL1,
      which are required for their efficient activation of mTOR signaling. Mutation of
      Rheb and RhebL1 at N41 impaired their interaction with mTOR, which identifies
      mTOR as a common downstream target of both Rheb and RhebL1.

PMID- 16098515
TI  - GABA, progesterone and zona pellucida activation of PLA2 and regulation by MEK
      ERK1/2 during acrosomal exocytosis in guinea pig spermatozoa.
AB  - We investigated whether GABA activates phospholipase A2 (PLA2) during acrosomal
      exocytosis, and if the MEK-ERK1/2 pathway modulates PLA2 activation initiated by
      GABA, progesterone or zona pellucida (ZP). In guinea pig spermatozoa prelabelled
      with [14C]arachidonic acid or [14C]choline chloride, GABA stimulated a decrease
      in phosphatidylcholine (PC), and release of arachidonic acid and lysoPC, during
      exocytosis. These lipid changes are indicative of PLA2 activation and appear
      essential for exocytosis since inclusion of aristolochic acid (a PLA2 inhibitor)
      abrogated them, along with exocytosis. GABA activation of PLA2 seems to be
      mediated, at least in part, by diacylglycerol (DAG) and protein kinase C since
      inclusion of the DAG kinase inhibitor R59022 enhanced PLA2 activity and
      exocytosis stimulated by GABA, whereas exposure to staurosporine decreased both.
      GABA-, progesterone- and ZP-induced release of arachidonic acid and exocytosis
      were prevented by U0126 and PD98059 (MEK inhibitors). Taken together, our results
      suggest that PLA2 plays a fundamental role in agonist-stimulated exocytosis and
      that MEK-ERK1/2 are involved in PLA2 regulation during this process.

PMID- 16098516
TI  - Characterization of a poplar NIMA-related kinase PNek1 and its potential role in
      meristematic activity.
AB  - Meristems are sites of undifferentiated cell division, which carry on developing
      into functional organs. Using the two-hybrid system with a poplar 14-3-3, we
      uncovered poplar NIMA-related kinase 1 (PNek1) as an interacting protein. PNek1
      shows high homology to the mammalian NIMA-related kinases, which are thought to
      be involved in cell cycle progression. Using a synchronized poplar cell
      suspension, we observed an accumulation of PNek1 mRNA at the G1/S transition and
      throughout the G2-to-M progression. Moreover, PNek1-GFP fusion protein localized
      in the cytoplasm and in both the nuclear and nucleolar regions. Overexpression of
      PNek1-GFP in Arabidopsis caused morphological abnormalities in flower and
      siliques. Overall, these results suggest that PNek1 is involved in plant
      development.

PMID- 16098517
TI  - X-ray structure of the gamma-subunit of a dissimilatory sulfite reductase: fixed
      and flexible C-terminal arms.
AB  - The X-ray structure of the gamma-subunit of the dissimilatory sulfite reductase
      (DsrC) from Archaeoglobus fulgidus was determined at 1.12 and 2.1A resolution, in
      the two crystal forms named DsrC(nat) and DsrC(ox) the latter being
      cocrystallized with the oxidizing agent tert-butyl hydroperoxide. The fold
      corresponds to that of the homologous protein from Pyrobaculum aerophilum but is
      significantly more compact. The most interesting, highly conserved C-terminal arm
      adopts a well-defined conformation in A. fulgidus DsrC in contrast to the
      completely disordered conformation in P. aerophilum DsrC. The functional
      relevance of both conformations and of a potentially redox-active disulfide bond
      between the strictly invariant Cys103 and Cys114 are discussed.

PMID- 16098518
TI  - Implication of a critical residue (Glu175) in structure and function of bacterial
      luciferase.
AB  - Structural properties of a bacterial luciferase mutant, evolved by random
      mutagenesis, have been investigated. Bacterial luciferases (LuxAB) can be readily
      classed as slow or fast decay luciferases based on their rates of luminescence
      decay in a single turnover assay. By random mutagenesis, one of the mutants
      generated by a single mutation on LuxA at position 175 (E175G) resulted in the
      "slow decay" Xenorhabdus luminescens luciferase was converted into a luciferase
      with a significantly more rapid decay rate [Hosseinkhani, S., Szittner, R. and
      Meighen, E.A. (2005) Biochemical Journal 385, 575-580]. A single mutation
      (E175G), in a loop that connects alpha helix 5 and beta sheet 5 brought about
      changes in the kinetic and structural properties of the enzyme. Enhancement of
      tryptophan fluorescence was observed with a lower degree of fluorescence
      quenching by acrylamide upon mutation. Near- and far-UV circular dichroism
      spectra of the native and mutant forms suggested formation of an intermediate
      structure, further supported by 8-anilino-1-naphthalene-sulphonic acid (ANS)
      fluorescence which indicated lower exposure of hydrophobic residues as a result
      of mutation. Fluorescence quenching studies utilizing acrylamide indicated a more
      accessible fluor for the native form. Thus, the E175G point mutation appears to
      change the enzymatic decay rate by inducing a substantial tertiary structural
      change, without a large effect on secondary structural elements, as revealed by
      Fourier transform IR spectroscopy. Overall, the mutation caused structural
      changes that go beyond the simple change in orientation of Glu175.

PMID- 16098519
TI  - Mammalian NHE2 Na(+)/H+ exchanger mediates efflux of potassium upon heterologous
      expression in yeast.
AB  - Na(+)/H+exchangers form a broad family of transporters that mediate opposing
      fluxes of alkali metal cations and protons across cell membranes. They play
      multiple roles in different organisms (protection from toxic cations, regulation
      of cell volume or pH). Rat NHE2 exchanger was expressed in a Saccharomyces
      cerevisiae mutant strain lacking its own exporters of alkali metal cations.
      Though most of the overexpressed NHE2 remained entrapped in the secretory
      pathway, part of it reached the plasma membrane and mediated K+ efflux from the
      yeast. We demonstrate for the first time that a mammalian Na(+)/H+ exchanger
      transports alkali metal cations in yeast in the opposite direction than in
      mammalian cells, and that the substrate specificity of the rat NHE2 exchanger is
      limited only to potassium cations upon expression in yeast cells.

PMID- 16098520
TI  - Maturation of Borna disease virus glycoprotein.
AB  - The maturation of Borna disease virus (BDV) glycoprotein GP was studied in regard
      to intracellular compartmentalization, compartmentalization signal-domains,
      proteolytic processing, and packaging into virus particles. Our data show that
      BDV-GP is (i) predominantly located in the endoplasmic reticulum (ER), (ii)
      partially exists in the ER already as cleaved subunits GP-N and GP-C, (iii) is
      directed to the ER/cis-Golgi region by its transmembrane and/or cytoplasmic
      domains in CD8-BDV-GP hybrid constructs and (iv) is incorporated in the virus
      particles as authentic BDV glycoprotein exclusively in the cleaved form decorated
      with N-glycans of the complex type. Downregulation of BDV-glycoproteins on the
      cell surface, their limited proteolytic processing, and protection of antigenic
      epitopes on the viral glycoproteins by host-identical N-glycans are different
      strategies for persistent virus infections.

PMID- 16098521
TI  - CO: A chemical ontology for identification of functional groups and semantic
      comparison of small molecules.
AB  - A novel chemical ontology based on chemical functional groups automatically,
      objectively assigned by a computer program, was developed to categorize small
      molecules. It has been applied to PubChem and the small molecule interaction
      database to demonstrate its utility as a basic pharmacophore search system.
      Molecules can be compared using a semantic similarity score based on functional
      group assignments rather than 3D shape, which succeeds in identifying small
      molecules known to bind a common binding site. This ontology will serve as a
      powerful tool for searching chemical databases and identifying key functional
      groups responsible for biological activities.

PMID- 16098522
TI  - Mutational analysis of the active center of plant fructosyltransferases: Festuca
      1-SST and barley 6-SFT.
AB  - The active center of the glycoside hydrolase family 32 contains the three
      characteristic motifs (N/S)DPNG, RDP, and EC. We replaced the N-terminal region
      including the (N/S)DPNG motif of barley 6-SFT (sucrose:fructan 6
      fructosyltransferase) by the corresponding region of Festuca 1-SST
      (sucrose:sucrose 1-fructosyltransferase). The chimeric enzyme, expressed in
      Pichia, retained the specificity of 6-SFT. Attempts to replace a larger piece at
      the N-terminus including also the RDP motif failed. A point mutation introduced
      in the RDP motif of 1-SST abolished enzymatic activity. Interestingly, point
      mutations of the EC-motif resulted in an enzyme which had lost the capability to
      form 1-kestose and glucose from sucrose but still accepted 1-kestose, producing
      fructose and sucrose as well as nystose.

PMID- 16098523
TI  - The upstream area of the chicken alpha-globin gene domain is transcribed in both
      directions in the same cells.
AB  - It was demonstrated previously that in erythroid chicken cells an extended
      upstream area of the alpha-globin gene domain is transcribed in both directions
      as a part of ggPRX gene and a part of a full domain transcript of the alpha
      globin gene domain. Here, we show that both DNA chains of the above-mentioned
      region are transcribed in the same cells and that the corresponding transcripts
      coexist in nuclei. The data obtained suggest that cells possess a molecular
      mechanism which in some cases prevents the formation of dsRNA and subsequent
      destruction of both transcripts in spite of the presence of complementary RNA
      chains in the cell nucleus.

PMID- 16098524
TI  - The Drosophila type II receptor, Wishful thinking, binds BMP and myoglianin to
      activate multiple TGFbeta family signaling pathways.
AB  - Wishful thinking (Wit) is a Drosophila transforming growth factor-beta (TGFbeta)
      superfamily type II receptor most related to the mammalian bone morphogenetic
      protein (BMP) type II receptor, BMPRII. To better understand its function, we
      undertook a biochemical approach to establish the ligand binding repertoire and
      downstream signaling pathway. We observed that BMP4 and BMP7, bound to receptor
      complexes comprised of Wit and the type I receptor thickveins and saxophone to
      activate a BMP-like signaling pathway. Further we demonstrated that both
      myoglianin and its most closely related mammalian ligand, myostatin, interacted
      with a Wit and Baboon (Babo) type II-type I receptor complex to activate
      TGFbeta/activin-like signaling pathways. These results thereby demonstrate that
      Wit binds multiple ligands to activate both BMP and TGFbeta-like signaling
      pathways. Given that myoglianin is expressed in muscle and glial-derived cells,
      these results also suggest that Wit may mediate myoglianin-dependent signals in
      the nervous system.

PMID- 16098525
TI  - Oxidative stress and metal ions effects on the cores of phycobilisomes in
      Synechocystis sp. PCC 6803.
AB  - Inactivation of the chlN gene in Synechocystis sp. PCC 6803 resulted in no
      chlorophyll and photosystems when the mutant was grown in darkness, providing an
      in vivo system to study the structure and function of phycobilisomes (PBSs). The
      effects of hydrogen peroxide (H2O2) and metal ions on the mutant PBSs in vivo
      were investigated by low temperature fluorescence emission measurement. H2O2
      induced an obvious disassembly of the cores of PBSs and interruption of energy
      transfer from allophycocyanin to the terminal emitter. Among many metal ions only
      silver induced disassembly of the cores of PBSs. Our results demonstrated for the
      first time that the cores of PBSs act as targets in vivo for oxidative stress or
      silver induced damage.

PMID- 16098526
TI  - The yeaS (leuE) gene of Escherichia coli encodes an exporter of leucine, and the
      Lrp protein regulates its expression.
AB  - Overexpression of the yeaS gene encoding a protein belonging to the RhtB
      transporter family conferred upon cells resistance to glycyl-l-leucine, leucine
      analogues, several amino acids and their analogues. yeaS overexpression promoted
      leucine and, to a lesser extent, methionine and histidine accumulation by the
      respective producing strains. Our results indicate that yeaS encodes an exporter
      of leucine and some other structurally unrelated amino acids. The expression of
      yeaS (renamed leuE for "leucine export") was induced by leucine, l-alpha-amino-n
      butyric acid and, to a lesser extent, by several other amino acids. The global
      regulator Lrp mediated this induction.

PMID- 16098527
TI  - Mechanism of direct degradation of IkappaBalpha by 20S proteasome.
AB  - IkappaBalpha regulates activation of the transcription factor NF-kappaB. NF
      kappaB is activated in response to several stimuli, i.e. proinflamatory
      cytokines, infections, and physical stress. This signal dependent pathway
      involves IkappaBalpha phosphorylation, ubiquitylation, and degradation by 26S
      proteasome. A signal independent (basal) turnover of IkappaBalpha has also been
      described. Here, we show that IkappaBalpha can be directly degraded by 20S
      proteasomes. Deletion constructs of IkappaBalpha allow us to the determine that N
      terminal (DeltaN 1-70) and C-terminal regions (DeltaC 280-327, removing the PEST
      region) of IkappaBalpha are not required for IkappaBalpha degradation, while a
      further C-terminal deletion including part of the arm repeats (DeltaC2 245-327)
      almost completely suppress the degradation by 20S proteasome. Binding and
      competition experiments demonstrate that the degradation of IkappaBalpha involves
      specific interactions with alpha2(C3) subunit of the proteasome. Finally,
      p65/relA (not itself a substrate for 20S proteasome) inhibits the degradation of
      IkappaBalpha by the proteasome. These results recapitulate in vitro the main
      characteristics of signal independent (basal) turnover of IkappaBalpha
      demonstrated in intact cells.

PMID- 16098528
TI  - Oxidized phospholipids induce phase separation in lipid vesicles.
AB  - The thermal behaviour of phospholipid multilamellar vesicles (MLV) made of
      various molar percentages of DPPC and LPPC, containing also oxidized LPPC
      (LPPCox), was studied by use of EPR spectroscopy and n-DSPC spin label in order
      to determine variations in the membrane fluidity brought about by lipid
      oxidation. Experimental variables were temperature, ranging from 4 to 44 degrees
      C, and molar percentage composition of DPPC/LPPC/LPPCox ternary mixture. We found
      that the presence of LPPCox in a percentage higher than both normal
      phospholipids' heavily hindered membrane formation, while lower percentage of the
      oxidized lipid with higher DPPC percentages yielded two-components EPR spectra,
      showing the presence of two different fluidity domains, indicative of membrane
      phase separation. When LPPC was the dominant lipid in the ternary mixture, simple
      EPR spectra were observed, indicating homogeneity of MLV membranes. Phase
      separation observed in the presence of LPPCox was better visible at lower
      temperature (12 degrees C or less), and almost disappeared with increasing
      temperature (36 degrees C or more). Furthermore, the correlation time of 16-DSPC
      in ternary mixture MLVs with higher LPPC percentage (homogeneous membranes) was
      not affected by the presence of LPPCox, while it normally increased upon DPPC
      percentage increase, as readily calculated from the EPR spectra featuring simple
      bands at 24 degrees C. It is concluded that oxidized lipid induces phase
      separation in more rigid DPPC-rich membranes, while leaving fluidity unaffected
      in more fluid LPPC-rich membranes, and at higher temperature.

PMID- 16098529
TI  - Bilateral retinal detachment in preeclamptic women with thrombophilia.

PMID- 16098530
TI  - Berberine inhibits rat vascular smooth muscle cell proliferation and migration in
      vitro and improves neointima formation after balloon injury in vivo. Berberine
      improves neointima formation in a rat model.
AB  - Berberine, an alkaloid isolated from Chinese medicinal herbs, long been known for
      its anti-microbial activity and used to treat various infectious disorders in
      traditional Chinese medicine. In the present study, we have tested the hypothesis
      that berberine could inhibit vascular smooth muscle cell (VSMC) proliferation as
      it did in endothelial cells or cancer cells. Our results show that berberine
      significantly inhibits growth factor, mainly angiotensin II (AngII) and heparin
      binding epidermal growth factor (HB-EGF), induced VSMC proliferation and
      migration in vitro, and this effect is achieved by delaying or partially
      suppressing activation of Akt pathway rather than ERK pathway. Furthermore, we
      have examined its effect in vivo using a rat carotid artery injury model. A 28
      days of chronic berberine treatment using an osmotic pump (100 microg kg(-1)d(
      1), 2 weeks before and 2 weeks after the injury) improved neointima formation.
      The Neointima/Media ratio for control group and berberine treated group were
      1.14+/-0.11 and 0.85+/-0.06 (p<0.05), respectively, and the reduction was
      approximately 25%. The result of the present study suggests a possibility of
      berberine being a potent agent to control restenosis after balloon angioplasty
      and warrants further study to gain a more complete understanding of its
      underlying mechanisms at a cellular level.

PMID- 16098531
TI  - Effects of rosuvastatin on postprandial leukocytes in mildly hyperlipidemic
      patients with premature coronary sclerosis.
AB  - We investigated whether pro-inflammatory aspects of the postprandial phase can be
      modulated by rosuvastatin in premature coronary artery disease (CAD) patients.
      Herefore standardized 8 h oral fat loading tests were performed off-treatment and
      after rosuvastatin 40 mg/d in 20 male CAD patients (50 +/- 4 years). The
      expression of leukocyte activation markers CD11a, CD11b, CD62L and CD66b was
      studied using flowcytometry. Migration of isolated neutrophils towards
      chemoattractants was determined in a fluorescence-based assay. Rosuvastatin did
      not affect baseline leukocyte counts nor the postprandial neutrophil increment
      (maximum mean increase +10% pre- and +14% post-treatment, P < 0.01 for each).
      Rosuvastatin reduced baseline platelets (from 266 +/- 78 to 225 +/- 74 x 10(9)
      cells/L, P < 0.001) and blunted the postprandial platelet count change (maximum
      mean increase +6%, P = 0.01, and 0%, respectively). The baseline expression of
      CD11a, CD11b and CD62L increased on most types of leukocytes by rosuvastatin,
      whereas the postprandial responses were unaffected. Pretreatment, postprandial
      neutrophil migration increased dose-dependently, but there were no postprandial
      changes after rosuvastatin. The latter effect was unrelated to changes in
      lipoprotein concentrations. In conclusion, in CAD patients postprandial pro
      inflammatory and pro-coagulant changes can be modified by rosuvastatin. These
      apparently lipid-lowering independent effects may render protection against
      atherosclerosis.

PMID- 16098532
TI  - High-density lipoprotein antagonizes oxidized low-density lipoprotein by
      suppressing oxygen free-radical formation and preserving nitric oxide
      bioactivity.
AB  - The antiatherogenic role of high-density lipoprotein (HDL) has been related to
      its ability to increase the activity of endothelial nitric oxide synthase (eNOS)
      and to protect low-density lipoprotein (LDL) against oxidative modification. The
      present study was aimed to determine whether and how HDL antagonizes oxidized LDL
      (oxLDL) that has been formed and accumulated in circulation. Pre-infusion of rats
      with HDL effectively prevented oxLDL-induced renal vascular constriction.
      Consistently, pre-incubation of human saphenous vein endothelial cells with HDL
      (100 microg/ml) reversed the oxLDL-induced suppression of endothelium-dependent
      cyclic-GMP production in co-cultured smooth muscle cells. However, the changes of
      Akt phosphorylation and eNOS activity in endothelial cells in response to
      lipoprotein treatments under our assay condition were not significant.
      Intriguingly, pretreatment of human umbilical vein endothelial cells with HDL (50
      microg/ml) for only 30s effectively reduced the level of free radicals generated
      by oxLDL or H(2)O(2). In kidneys of living rats, renal arterial infusion of oxLDL
      greatly enhanced ischemia/reperfusion-induced free radicals, which could be
      attenuated by HDL pretreatment. We conclude that HDL may antagonize oxLDL on
      endothelial function through an Akt-independent pathway in which HDL preserves
      nitric oxide bioactivity by attenuating oxLDL-triggered free radical generation.

PMID- 16098533
TI  - Computational fluid dynamics modeling of the upper airway of children with
      obstructive sleep apnea syndrome in steady flow.
AB  - Computational fluid dynamic (CFD) analysis was used to model the effect of airway
      geometry on internal pressure in the upper airway of three children with
      obstructive sleep apnea syndrome (OSAS), and three controls. Model geometry was
      reconstructed from magnetic resonance images obtained during quiet tidal
      breathing, meshed with an unstructured grid, and solved at normative peak resting
      flow. The unsteady Reynolds-averaged Navier-Stokes equations were solved with
      steady flow boundary conditions in inspiration and expiration, using a two
      equation low-Reynolds number turbulence model. Model results were validated using
      an in-vitro scale model, unsteady flow simulation, and reported nasal resistance
      measurements in children. Pharynx pressure drop strongly correlated to airway
      area restriction. Inspiratory pressure drop was primarily proportional to the
      square of flow, consistent with pressure losses due to convective acceleration
      caused by area restriction. On inspiration, in OSAS pressure drop occurred
      primarily between the choanae and the region where the adenoids overlap the
      tonsils (overlap region) due to airway narrowing, rather than in the nasal
      passages; in controls the majority of pressure drop was in the nasal passages. On
      expiration, in OSAS the majority of pressure drop occurred between the oropharynx
      (posterior to the tongue) and overlap region, and local minimum pressure in the
      overlap region was near atmospheric due to pressure recovery in the anterior
      nasopharynx. The results suggest that pharyngeal airway shape in children with
      OSAS significantly affects internal pressure distribution compared to nasal
      resistance. The model may also help explain regional dynamic airway narrowing
      during expiration.

PMID- 16098534
TI  - The CCAAT-binding complex of eukaryotes: evolution of a second NLS in the HapB
      subunit of the filamentous fungus Aspergillus nidulans despite functional
      conservation at the molecular level between yeast, A.nidulans and human.
AB  - The heterotrimeric CCAAT-binding complex is evolutionarily conserved in
      eukaryotic organisms, including fungi, plants and mammals. In the filamentous
      fungus Aspergillus nidulans, the corresponding complex was designated AnCF
      (A.nidulans CCAAT-binding factor). AnCF consists of the subunits HapB, HapC and
      HapE. All three subunits are necessary for DNA binding. HapB contains two
      putative nuclear localisation signal sequences (NLSs) designated NLS1 and NLS2.
      Previously, it was shown that only NLS2 was required for nuclear localisation of
      HapB. Furthermore, HapC and HapE are transported to the nucleus only in complex
      with HapB via a piggy back mechanism. Here, by using various GFP constructs and
      by establishing a novel marker gene for transformation of A.nidulans, i.e. the
      pabaA gene encoding p-aminobenzoic acid synthase, it was shown that the HapB
      homologous proteins of both Saccharomyces cerevisiae (Hap2p) and human (NF-YA)
      use an NLS homologous to HapB NLS1 for nuclear localisation in S.cerevisiae.
      Interestingly, for A.nidulans HapB, NLS1 was sufficient for nuclear localisation
      in S.cerevisiae. In A.nidulans, HapB NLS1 was also functional when present in a
      different protein context. However, in A.nidulans, both S.cerevisiae Hap2p and
      human NF-YA entered the nucleus only when HapB NLS2 was present in the respective
      proteins. In that case, both proteins Hap2p and NF-YA complemented, at least in
      part, the hap phenotype of A.nidulans with respect to lack of growth on
      acetamide. Similarly, A.nidulans HapB and human NF-YA complemented a hap2 mutant
      of S.cerevisiae. In summary, HapB, Hap2p and NF-YA are interchangeable. Because
      the A.nidulans hapB mutant was complemented, at least in part, by both the human
      NF-YA and S.cerevisiae Hap2p this finding suggests that the piggy-back mechanism
      of nuclear transport found for A.nidulans is conserved in yeast and human.

PMID- 16098535
TI  - Kinetically controlled thermal response of beta2-microglobulin amyloid fibrils.
AB  - Calorimetric measurements were carried out using a differential scanning
      calorimeter in the temperature range from 10 to 120 degrees C for characterizing
      the thermal response of beta2-microglobulin amyloid fibrils. The thermograms of
      amyloid fibril solution showed a remarkably large decrease in heat capacity that
      was essentially released upon the thermal unfolding of the fibrils, in which the
      magnitude of negative heat capacity change was not explicable in terms of the
      current accessible surface area model of protein structural thermodynamics. The
      heat capacity-temperature curve of amyloid fibrils prior to the fibril unfolding
      exhibited an unusual dependence on the fibril concentration and the heating rate.
      Particularly, the heat needed to induce the thermal response was found to be
      linearly dependent on the heating rate, indicating that its thermal response is
      under a kinetic control and precluding the interpretation in terms of equilibrium
      thermodynamics. Furthermore, amyloid fibrils of amyloid beta peptides also
      exhibited a heating rate-dependent exothermic process before the fibril
      unfolding, indicating that the kinetically controlled thermal response may be a
      common phenomenon to amyloid fibrils. We suggest that the heating rate-dependent
      negative change in heat capacity is coupled to the association of amyloid fibrils
      with characteristic hydration pattern.

PMID- 16098537
TI  - An introduction to obtaining extramural funding.
AB  - The ability to obtain extramural funding is a critical part of developing a
      successful academic career. This manuscript provides an introduction to the
      sources of funding, the process by which a research proposal is developed, and
      the process by which a research proposal is reviewed and funding. Emphasis is
      placed on the process of grant review is performed at the National Institutes of
      Health.

PMID- 16098536
TI  - Citation characteristics of basic science research publications in general
      surgical journals.
AB  - BACKGROUND: Basic science research (BSR) publications in general surgical (GS)
      journals are an important "translational bridge" for practicing surgeons and
      surgical trainees. The purpose of this study is to characterize the BSR
      publications in GS journals and to analyze their citation frequencies. METHODS:
      In 1996, all (224) BSR publications in the five highest rated U.S. GS journals
      (by impact factor) were reviewed, characterized, and their citation frequencies
      were compared to BSR publications in non-GS journals. RESULTS: On average, a BSR
      publication from these journals is cited 32 times (range 1-141, median 11). Half
      of the publications were cited more than 10 times in 6 years and 22% were cited
      twice, or more, within 1 year of publication. One in four publications were cited
      twice or more in journals with an impact factor greater than five. Citation
      frequencies of BSR publications in GS journals were related to the journal impact
      factor (P = 0.07), and to having a basic scientist (i.e., Ph.D.) as one of the
      authors (P < 0.01). Citation characteristics of BSR publications in GS journals
      were similar to those of BSR publications in non-GS journals with similar impact
      factors. CONCLUSIONS: We found that BSR publications in the U.S. GS journals
      studied had significant citation frequencies.

PMID- 16098538
TI  - Determinants of simulated RNA evolution.
AB  - Models of RNA secondary structure folding are widely used to study evolution in
      theory and simulation. However, systematic studies of the parameters involved are
      rare. In this paper, we study by simulation how RNA evolution is influenced by
      three different factors, namely the mutation rate, scaling of the fitness
      function, and distance measure. We found that for low mutation rates the
      qualitative evolutionary behavior is robust with respect to the scaling of the
      fitness function. For efficient mutation rates, which are close to the error
      threshold, scaling and distance measure have a strong influence on the
      evolutionary behavior. A global distance measure that takes sequence information
      additively into account lowers the error threshold. When using a local sequence
      structure alignment for the distance, we observed a smoother evolution of the
      fitness over time. Finally, in addition to the well known error threshold, we
      identify another threshold of the mutation rate, called divergence threshold,
      where the qualitative transient behavior changes from a localized to an
      exploratory search.

PMID- 16098539
TI  - A mathematical model of intracranial pressure dynamics for brain hypothermia
      treatment.
AB  - Brain hypothermia treatment is used as a neuroprotectant to decompress the
      elevated intracranial pressure (ICP) in acute neuropatients. However, a
      quantitative relationship between decompression and brain hypothermia is still
      unclear, this makes medical treatment difficult and ineffective. The objective of
      this paper is to develop a general mathematical model integrating hemodynamics
      and biothermal dynamics to enable a quantitative prediction of transient
      responses of elevated ICP to ambient cooling temperature. The model consists of a
      lumped-parameter compartmental representation of the body, and is based on two
      mechanisms of temperature dependence encountered in hypothermia, i.e. the van't
      Hoff's effect of metabolism and the Arrhenius' effect of capillary filtration.
      Model parameters are taken from the literature. The model is verified by
      comparing the simulation results to population-averaged data and clinical
      evidence of brain hypothermia treatment. It is possible to assign special model
      inputs to mimic clinical maneuvers, and to adjust model parameters to simulate
      pathophysiological states of intracranial hypertension. Characteristics of
      elevated ICP are quantitatively estimated by using linear approximation of step
      response with respect to ambient cooling temperature. Gain of about 4.9 mmHg
      degrees C(-1), dead time of about 1.0 h and a time constant of about 9.8h are
      estimated for the hypothermic decompression. Based on the estimated
      characteristics, a feedback control of elevated ICP is introduced in a simulated
      intracranial hypertension of vasogenic brain edema. Simulation results suggest
      the possibility of an automatic control of the elevated ICP in brain hypothermia
      treatment.

PMID- 16098540
TI  - Integration of cell adhesion reactions--a balance of forces?
AB  - The rearrangement of receptors by oligomeric adhesion molecules constitutes a
      configurational mechanism able to sculpture membranes and dislocate receptors
      from cytoplasmic anchorage. This provides a conceptual framework for complex
      cellular processes in mechanical terms, as a dynamic balance between
      extracellular and intracellular driving forces.

PMID- 16098541
TI  - Assessing surface water quality of the Yangtze Estuary with genotoxicity data.
AB  - The present study investigated the genotoxicity of the surface water samples from
      the Yangtze Estuary with the Ames test in three seasons. Several important
      chemical parameters, such as COD inorganic nitrogen, active phosphate and heavy
      metals, were also analyzed at the same time. According the results, surface water
      samples from the south branch and a few of samples at the seaward end of the
      Yangtze Estuary show positive genotoxicity in some seasons. Chemical analysis
      revealed that the Yangtze Estuary was seriously polluted by inorganic nitrogen
      and by active phosphate. However, chemical parameters could not demonstrate the
      spatial variation of water quality of the estuary, and they could not assess
      adverse effects of chemicals in mixtures as well. Therefore, it is recommended
      that genotoxicity data, mutation rate of the Salmonella typhimurium strain TA98
      at the dose of 1l per plate, be taken as a new parameter assessing surface water
      quality of the Yangtze Estuary. Our studies also suggested that genetic
      toxicology assays, such as the Ames test, could be applied as a routine measure
      to monitoring marine environment in China. The paper proposes a development of
      the National Seawater Quality Standard of China.

PMID- 16098542
TI  - Lack of a difference in increased capillary blood cell velocity in the skin over
      proximal interphalangeal joints between rheumatoid arthritis and osteoarthritis.
AB  - Early detection of synovitis in rheumatoid arthritis (RA) and distinction from
      osteoarthritis (OA) are important to establish the most appropriate treatment.
      Increased perfusion over affected joints observed by laser Doppler perfusion
      imaging was supposed to arise from the underlying joint, because it was detected
      only by a near-infrared laser and not by a less penetrating red laser source.
      Using laser Doppler anemometry, this study addressed two questions: (1) whether
      capillary blood cell velocity (CBV) is increased in the skin over finger joints
      affected by RA or OA; (2) whether there is a difference between RA and OA in CBV
      above affected proximal interphalangeal (PIP) joints. Levels of soluble adhesion
      molecules were measured, because they indicate rheumatoid vasculitis raising flow
      resistance. Thirty-one patients with RA and 20 with OA were investigated.
      Compared to 18 controls, CBV (mean+/-SEM) was elevated above PIP joints
      clinically affected by RA (0.35+/-0.06 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and
      over PIP (0.27+/-0.02 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and distal
      interphalangeal joints (0.27+/-0.02 mm/s vs. 0.17+/-0.01 mm/s; P<0.001) affected
      by OA. Levels of soluble adhesion molecules were not correlated with CBV over PIP
      joints in RA. These observations demonstrated that elevated blood cell velocity
      is detectable by laser Doppler anemometry in skin capillaries over
      interphalangeal joints affected by RA or OA and contradict the previous
      assumption that there is hyperemia only in the affected joint. The lack of a
      significant difference in CBV over PIP joints between RA and OA patients might be
      due to some inflammation also occurring in OA rather than to vasculitic processes
      in RA associated with elevated levels of soluble adhesion molecules.

PMID- 16098543
TI  - Working memory and semantic involvement in sentence processing: a case of pure
      progressive amnesia.
AB  - ED, a 83-year-old woman, meets the criteria of pure progressive amnesia, with
      gradual impairment of episodic and autobiographical memory, sparing of semantic
      processing and strong working memory (WM) deficit. The dissociation between
      disturbed WM and spared semantic processing permitted testing the role of WM in
      processing anaphors like pronouns or repeated names. Results showed a globally
      normal anaphoric behavior in two experiments requiring anaphoric processing in
      sentence production and comprehension. We suggest that preserved semantic
      processing in ED would have compensated for working memory deficit in anaphoric
      processing.

PMID- 16098544
TI  - Single experience learning of host fruit selection by lepidopteran larvae.
AB  - Neonate larvae of a lepidopteran, the codling moth (Cydia pomonella L.) search
      for their host fruit after hatch. The process of host searching is known to be
      activated by kairomones contained in host fruit volatiles, but the mechanism of
      actual selection and infestation of the fruit is unclear. Here we show that
      lepidopteran neonates can utilize single experience learning in selection and
      infestation of host apple. We found that the process of host fruit selection may
      be modified by single experience learning, namely preference induction or averse
      conditioning. Both types of learning were acquired within 3 h of training.
      Experience was retained for over 3 days in the case of averse conditioning.
      Preference induction, a form of learning specific to insects, is expected to
      produce rigid host preference lasting for days if not weeks, but in codling moth
      neonates this type of memory was retained only for 3 h. We speculate that
      conjunction of preference induction with short retention time and averse
      conditioning with long retention time provide an optimal adaptive strategy of
      host fruit selection for codling moth neonates.

PMID- 16098545
TI  - The perirhinal cortex of the rat is necessary for spatial memory retention long
      after but not soon after learning.
AB  - Many observations in humans and experimental animals support the view that the
      hippocampus is critical immediately after learning in order for long-term memory
      formation to take place. However, exactly when the medial temporal cortices
      adjacent to the hippocampus are necessary for this process to occur normally is
      not yet well known. Using a spatial task, we studied whether the perirhinal
      cortex of rats is necessary to establish representations in long-term memory.
      Results showed that, in a spatial task sensitive to hippocampal lesions, control
      and perirhinal lesioned rats can both learn at the same rate (Experiment 1).
      Interestingly, a differential involvement of the perirhinal cortex in memory
      retention was observed as time passes after learning. Thus, 24 days following the
      end of learning, lesioned and control rats remembered the task perfectly as
      measured by a retraining test. In contrast, 74 days after the learning the
      perirhinal animals showed a profound impairment in the retention of the spatial
      information (Experiment 2). Taken together, these results suggest that the
      perirhinal region is critical for the formation of long-term spatial memory.
      However, its contribution to memory formation and retention is time-dependent, it
      being necessary only long after learning takes place and not during the phase
      immediately following acquisition.

PMID- 16098546
TI  - Feather pecking in chickens is genetically related to behavioural and
      developmental traits.
AB  - Feather pecking (FP) is a detrimental behaviour in chickens, which is performed
      by only some individuals in a flock. FP was studied in 54 red junglefowl
      (ancestor of domestic chickens), 36 White Leghorn laying hens, and 762 birds from
      an F(2)-intercross between these two lines. From all F(2)-birds, growth and feed
      consumption were measured. Age at sexual maturity and egg production in females,
      and corticosterone levels in males were also measured. From 333 F(2)-birds of
      both sexes, and 20 parental birds, body composition with respect to bone mineral
      content, muscle and fat was obtained by post-mortem examinations using Dual X-Ray
      Absorptiometry (DXA). In femurs of the same birds, the bone density and structure
      were analysed using DXA and Peripheral Quantitative Computerized Tomography
      (pQCT), and a biomechanical analysis of bone strength was performed. Furthermore,
      plumage condition was determined in all birds as a measure of being exposed to
      feather pecking. Using 105 DNA-markers in all F(2)-birds, a genome-wide scan for
      Quantitative Trait Loci (QTL), associated with the behaviour in the F(2)
      generation was performed. FP was at least as frequent in the red junglefowl as in
      the White Leghorn strain studied here, and significantly more common among
      females both in the parental strains and in the F(2)-generation. In the F(2)
      birds, FP was phenotypically linked to early sexual maturation, fast growth, weak
      bones, and, in males, also high fat accumulation, indicating that feather peckers
      have a different resource allocation pattern. Behaviourally, F(2) feather peckers
      were more active in an open field test, in a novel food/novel object test, and in
      a restraint test, indicating that feather pecking might be genetically linked to
      a proactive coping strategy. Only one suggestive QTL with a low explanatory value
      was found on chromosome 3, showing that many genes, each with a small effect, are
      probably involved in the causation of feather pecking. There were significant
      effects of sire and dam on the risk of being a victim of feather pecking, and
      victims grew faster pre- and post-hatching, had lower corticosterone levels and
      were less active in a restraint test. Hence, a wide array of behavioural and
      developmental traits were genetically linked to FP.

PMID- 16098547
TI  - Cholecystokinin1 receptors mediate the increase in Fos-like immunoreactivity in
      the rat myenteric plexus following intestinal oleate infusion.
AB  - Intestinal infusion of nutrients, such as glucose and oleic acid, increase Fos
      like immunoreactivity (Fos-LI) in both the enteric nervous system and neurons of
      the dorsal vagal complex (DVC) of the hindbrain. To test the hypothesis that
      increased Fos-LI in enteric neurons and the DVC, following intestinal nutrient
      infusions is mediated by cholecystokinin(1) receptors (CCK(1)), we counted
      enteric and DVC neurons that expressed Fos-LI following intestinal infusion of
      oleate or glucose, with and without pretreatment with the CCK(1) receptor
      antagonist, lorglumide. Both oleate and glucose infusions increased Fos-LI in the
      DVC. Oleate also increased Fos-LI in the myenteric and submucosal plexuses of the
      duodenum and the jejunum, but not the ileum, while glucose only increased Fos-LI
      in the submucosal plexus of the ileum. The CCK(1) receptor antagonist,
      lorglumide, abolished Fos-LI in the DVC following infusions of either oleate or
      glucose. In addition, lorglumide attenuated oleate-induced Fos-LI in the
      myenteric and submucosal plexuses of the duodenum and jejunum. However,
      lorglumide failed to attenuate glucose-induced Fos-LI in the submucosal plexus of
      the ileum. These data confirm previous reports indicating that CCK(1) receptors
      mediate increased DVC Fos-LI following intestinal infusion of oleate or glucose.
      CCK(1) receptors also contribute to increased Fos-LI in enteric neurons following
      intestinal oleate infusion. However, failure of lorglumide to attenuate the
      increase of Fos-LI in the ileal submucosal plexus following intestinal glucose
      suggests that some intestinal nutrients trigger Fos-LI induction via CCK(1)
      receptor-independent pathways.

PMID- 16098548
TI  - Purification of an isoflavonoid 7-O-beta-apiosyl-glucoside beta-glycosidase and
      its substrates from Dalbergia nigrescens Kurz.
AB  - A beta-glycosidase was purified from the seeds of Dalbergia nigescens Kurz based
      on its ability to hydrolyse p-nitrophenyl beta-glucoside and beta-fucoside. This
      enzyme did not hydrolyze various glycosidic substrates efficiently, so it was
      used to identify its own natural substrates. Two substrates were identified,
      isolated and their structures determined as: compound 1, dalpatein 7-O-beta-D
      apiofuranosyl-(1-->6)-beta-D-glucopyranoside and compound 2, 6,2',4',5'
      tetramethoxy-7-hydroxy-7-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside
      (dalnigrein7-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside). The beta
      glycosidase removes the sugar from these glycosides as a disaccharide, despite
      its initial identification as a beta-glucosidase and beta-fucosidase.

PMID- 16098549
TI  - Mercury rising or 'Why is a raven like a writing desk?'.

PMID- 16098550
TI  - Immunodetection of the signal transducer and activator of transcription-3 in
      canine haemangioma and haemangiosarcoma.
AB  - The aim of this study was to examine the expression of signal transducer and
      activator of transcription 3 (STAT3) in canine haemangiomas and
      haemangiosarcomas. STAT3 protein was demonstrated in both the cytoplasm and
      nuclei of labelled cells. The expression of STAT3 was observed in 87.50% (35/40)
      of both haemangiomas and haemangiosarcomas and 72.22% (13/18) of haemangiomas and
      100% (22/22) haemangiosarcomas. The percentage of positive cells in haemangiomas
      and haemangiosarcomas was statistically significant difference (P<0.0001). These
      preliminary results indicate that STAT3 is overexpressed in malignant tumours.

PMID- 16098551
TI  - A clinical study of plasminogen activator activity in gingival tissue in dogs
      with gingivitis and periodontitis.
AB  - The aim of the present study was to evaluate plasminogen activator activity
      (PAA), tissue-type plasminogen activator (t-PA) antigen level and plasminogen
      activator inhibitor-1 (PAI-1) antigen in normal canine gingival tissue samples,
      gingivitis as well as in different stages of periodontal disease. Gingival tissue
      from 141 adult dogs were analysed spectrophotometrically in order to determine
      PAA. The tissues were also examined histopathologically. The Sulcus Bleeding
      Index was used to evaluate the active and inactive phase of periodontal disease.
      T-PA antigen as well as PAI-1 antigen level was measured by ELISA. There was a
      significant increase of PAA and t-PA antigen in samples from inflamed gingival
      tissue compared with normal gingival tissue, while PAI-1 antigen was not detected
      in either normal or inflamed gingiva. As the severity of periodontal disease was
      increasing, PAA and t-PA antigen values were significantly higher in
      periodontitis tissue sample groups, according to the pattern: gingivitis<early
      periodontitis<moderate periodontitis<severe periodontitis (P<0.001). PAA and t-PA
      antigen were increased in samples from the inflamed gingival tissue with higher
      Bleeding Index, (heavy bleeding>moderate bleeding>slight bleeding, P<0.001). In
      conclusion, this study indicates that PAA and t-PA antigen level may be used to
      evaluate the evolution of periodontal disease in dog.

PMID- 16098552
TI  - The use of impulse oscillometry for separate analysis of inspiratory and
      expiratory impedance parameters in horses: effects of sedation with xylazine.
AB  - AIM: To improve the outcome of parameters measured by the impulse oscillometry
      system (IOS) in horses by separate assessment of inspiratory and expiratory
      impedance spectra in the frequency range between 1 and 10 Hz. As basis for
      further studies, the influence of sedation with xylazine on respiratory impedance
      was also investigated. METHODS: (i) The respiratory impedance of 11 horses was
      measured using IOS before and 6 min after sedation (xylazine; 0.6 mg/kg b.w.).
      (ii) The time course of impedance parameters in a period of 24 min after
      administration of xylazine was evaluated in 12 horses at regular intervals of 3
      min. Resistance (R(rs)), reactance (X(rs)), and coherence (Co) were calculated as
      mean spectra (R(rs),X(rs),Co) of the entire measurement as well as separated into
      inspiration (Ri(rs),Xi(rs),Coi) and expiration (Re(rs),Xe(rs),Coe) at frequencies
      of 1, 5, and 10 Hz. RESULTS: (i) R(rs), X(rs) as well as Re(rs) and Xe(rs)
      revealed no significant influence of sedation. However, separate analysis of
      inspiration and expiration revealed a significant influence of sedation on all
      inspiratory impedance parameters. (ii) During the 24 min period after sedation,
      almost all inspiratory parameters were found significantly dependent on the time
      course of sedation whereas expiratory parameters Re10, Xe1, and Xe5 were not
      influenced. These results indicate that confounding factors due to sedation act
      mainly during inspiration. Muscle relaxation in upper airways due to xylazine is
      suspected to be the main cause of these phenomena.

PMID- 16098553
TI  - cDNA cloning of a novel P-I lebetase isoform Le-4.
AB  - In order to better understand the function of fibrinolytic enzyme lebetase
      isoforms and the synthesis of disintegrins we have isolated a cDNA encoding the
      most basic isoform (Le-4) from the cDNA library prepared from the poly(A)(+) RNA
      of the venomous gland of an individual Vipera lebetina snake. The truncated 5'
      sequence of 1112 basepairs encodes the mature protein with 203 amino acid
      residues with calculated isoelectric point and size of 5.6 and 22,930 Da,
      respectively. Multiple comparison of the deduced amino acid sequence of the
      metalloprotease part of Le-4 is related to short reprolysins, identities were
      within the range of 60--87%. The two lebetase isoforms are synthesized in
      different way: Le-4 is synthesized with metalloprotease domain only; Le-3 is
      synthesized with metalloprotease and disintegrin-like domain and processed
      posttranslationally. The sequence of the disintegrin-like part of Le-3 is
      identical to A-chain of the heterodimeric disintegrin VLO5 from Vipera lebetina
      obtusa venom (Calvete et al., 2003).

PMID- 16098554
TI  - Detection of microcystin synthetase genes in health food supplements containing
      the freshwater cyanobacterium Aphanizomenon flos-aquae.
AB  - In this study we investigated the presence of toxin-producing cyanobacterial
      contaminants in food supplements manufactured from blooms of the non-toxic
      freshwater cyanobacterium Aphanizomenon flos-aquae. Previous reports
      investigating the contamination of health food supplements with toxin-producing
      cyanobacteria have used chemical and or biochemical methods such as HPLC, ELISA
      and protein phosphatase assays. Whilst these studies have drawn attention to the
      presence of hepatotoxic microcystins in some commercially available food
      supplements, the methods used do not provide any information on the source of the
      contaminant. Such information would be useful for the quality control of food
      supplements produced for human consumption. In this study we applied a molecular
      technique, involving the amplification of the 16s rRNA gene, the phycocyanin
      operon, and two genes of the microcystin synthetase gene cluster to show that all
      12 food supplement samples, sourced from various internet distributors and
      containing non-toxic A. flos-aquae, also contained toxigenic cyanobacteria.
      Sequencing of the microcystin synthetase genes detected in all of the food
      supplements showed that M. aeruginosa was the organism responsible for the
      production of microcystins in the samples. The presence of microcystins in the
      food supplements was confirmed by ELISA, with concentrations within the range of
      0.1--4.72 microgg(-1) (microcystin-LR equivalents). Given that the molecular
      methods applied here are highly sensitive, and show good agreement with the
      results obtained from ELISA, we believe that they could potentially be used as a
      quality control technique for food products that contain cyanobacteria.

PMID- 16098555
TI  - Efficient expansion of HIV-1-specific T cell responses by homologous immunization
      with recombinant Semliki Forest virus particles.
AB  - Vaccines based on recombinant viruses represent a promising strategy for the
      development of a prophylactic vaccine against HIV-1. However, despite a proven
      capacity to stimulate potent HIV-1-specific immune responses, viral systems have
      limited utility in homologous prime-boost regimens due to the generation of anti
      vector immune responses. It is therefore important to develop a diverse set of
      vaccine candidates that can be combined in different heterologous prime-boost
      regimens and/or to identify a vaccine candidate that is less sensitive to anti
      vector mediated immunity. In this report, we describe the design and pre-clinical
      immunogenicity of a Semliki Forest virus-based vaccine, VREP-C, encoding Indian
      origin HIV-1 clade C antigens. We show that a single immunization with VREP-C
      stimulates HIV-1-specific IFNgamma ELISPOT responses, which were efficiently
      boosted by a second and a third homologous VREP-C immunization resulting in
      highly potent cytotoxic T cell responses. These results suggest that VREP-C may
      be a valuable component of a future prophylactic vaccine against HIV-1.

PMID- 16098556
TI  - The effect of pH on the competition between polyphosphate-accumulating organisms
      and glycogen-accumulating organisms.
AB  - In enhanced biological phosphorus removal (EBPR) processes, glycogen-accumulating
      organisms (GAOs) may compete with polyphosphate-accumulating organisms (PAOs) for
      the often-limited carbon substrates, potentially resulting in disturbances to
      phosphorus removal. A detailed investigation of the effect of pH on the
      competition between PAOs and GAOs is reported in this study. The results show
      that a high external pH ( approximately 8) provided PAOs with an advantage over
      GAOs in EBPR systems. The phosphorus removal performance improved due to a
      population shift favouring PAOs over GAOs, which was shown through both chemical
      and microbiological methods. Two lab-scale reactors fed with propionate as the
      carbon source were subjected to an increase in pH from 7 to 8. The phosphorus
      removal and PAO population (as measured by quantitative fluorescence in situ
      hybridisation analysis of "Candidatus Accumulibacter phosphatis") increased in
      each system, where the PAOs appeared to out-compete a group of
      Alphaproteobacteria GAOs. A considerable improvement in the P removal was also
      observed in an acetate fed reactor, where the GAO population (primarily
      "Candidatus Competibacter phosphatis") decreased substantially after a similar
      increase in the pH. The results from this study suggest that pH could be used as
      a control parameter to reduce the undesirable proliferation of GAOs and improve
      phosphorus removal in EBPR systems.

PMID- 16098557
TI  - The composition and relationships between trace element levels in inhalable
      atmospheric particles (PM10) and in leaves of Nerium oleander L. and Lantana
      camara L.
AB  - In order to evaluate the composition of inhalable atmospheric particles and to
      study the relationship between trace element levels in PM10 and in leaves of two
      plant species, the amount of Ba, Cu, Fe, Mn, Pb, Ti and V were analysed in PM10
      and in Nerium oleander L. and Lantana camara L. leaves from two sites in the city
      of Seville and one remote control site. In PM10, the Cu and Fe content was
      significantly lower (p<0.05) in the control site than in the other sites. No
      correlations between leaf content and air content were found for the elements in
      L. camara. On the contrary, positive and significant correlations (p<0.05) were
      found between leaf content of N. oleander and PM10 content for Cu and Fe. The
      data suggest that N. oleander can be used in atmospheric biomonitoring studies,
      because it is especially useful for Cu and Fe, N. oleander being a better
      indicator than L. camara.

PMID- 16098558
TI  - Effect of textile auxiliaries on the biodegradation of dyehouse effluent in
      activated sludge.
AB  - The textile industry is confronted with serious environmental problems associated
      with its immense wastewater discharge, substantial pollution load, extremely high
      salinity, and alkaline, heavily coloured effluent. Particular sources of
      recalcitrance and toxicity in dyehouse effluent are two frequently used textile
      auxiliaries; i.e. dye carriers and biocidal finishing agents. The present
      experimental work reports the observation of scientific and practical
      significance related with the effect of two commercially important textile dye
      carriers and two biocidal finishing agents on biological activated sludge
      treatment at a textile preparation, dyeing and finishing plant in Istanbul.
      Respirometric measurements of the dyehouse effluent spiked with the selected
      textile chemicals were carried out for the assessment of the "readily
      biodegradable COD fraction" of the wastewater. The respirometric data obtained to
      visualize the effect of the selected textile auxiliaries on biomass activity was
      evaluated by an adopted activated sludge model. Results have indicated that the
      tested biocides did not exert any significant inhibitory effect on the treatment
      performance of the activated sludge reactor at the concentrations usually
      encountered in the final, total dyehouse effluent. The situation with the dye
      carriers was inherently different; one dye carrier appeared to be highly toxic
      and caused serious inhibition of the microbial respirometric activity, whereas
      the other dye carrier, also known as the more ecological alternative, i.e. the
      "Eco-Carrier", appeared to be biodegradable. Finally, the respirometric profile
      obtained for the Eco-Carrier was described by a simplified respirometric model.

PMID- 16098559
TI  - Two bacterial strains isolated from a Zn-polluted soil enhance plant growth and
      mycorrhizal efficiency under Zn-toxicity.
AB  - In this study we investigated the interactions among plant, rhizosphere
      microorganisms and Zn pollution. We tested the influence of two bacterial strains
      isolated from a Zn-polluted soil on plant growth and on the symbiotic efficiency
      of native arbuscular mycorrhizal fungi (AMF) under Zn toxicity. The two bacterial
      strains exhibited Zn tolerance when cultivated under increasing Zn levels in the
      medium. However, strain B-I showed a higher Zn tolerance than strain B-II at the
      two highest Zn levels in the medium (75 and 100 mg l(-1) Zn). Molecular
      identification placed the strain B-I within the genus Brevibacillus. Our results
      showed that bacterial strain B-I consistently enhanced plant growth, N and P
      accumulation, as well as nodule number and mycorrhizal infection which
      demonstrated its plant-growth promoting (PGP) activity. This strain B-I has been
      shown to produce IAA (3.95 microg ml) and to accumulate 5.6% of Zn from the
      growing medium. The enhanced growth and nutrition of plants dually inoculated
      with the AMF and bacterium B-I was observed at three Zn levels assayed. This
      effect can be related to the stimulation of symbiotic structures (nodules and AMF
      colonization) and a decreased Zn concentration in plant tissues. The amount of Zn
      acquired per root weight unit was reduced by each one of these bacterial strains
      or AMF and particularly by the mixed bacterium-AMF inocula. These mechanisms
      explain the alleviation of Zn toxicity by selected microorganisms and indicate
      that metal-adapted bacteria and AMF play a key role enhancing plant growth under
      soil Zn contamination.

PMID- 16098560
TI  - Ionic liquid-containing semipermeable membrane devices for monitoring the
      polycyclic aromatic hydrocarbons in water.
AB  - Ionic liquid-containing semipermeable membrane devices (IL-SPMDs) were developed
      to monitor the polycyclic aromatic hydrocarbons in water. Uptake kinetics of
      naphthalene, 1-methylnaphthalene, phenanthrene, pyrene, chrysene by layflat low
      density polyethylene tubing (15 cm x 2 cm) filled with 0.5 ml 1-butyl-3
      methylimidazolium hexafluorophosphate ionic liquid were studied in a laboratory
      continuous-flow system for the duration of 16 days. The device concentration
      factors were in the range of 830-7800 for the studied PAHs. The kinetic
      parameters of IL/water partition coefficients, analytes uptake rate constants and
      sampling rates were estimated using mathematical models. These parameters were
      used in the field experiment to estimate the concentrations of the PAHs in
      Lanzhou section of Yellow River in China, with the result in comparison with that
      obtained by triolein-SPMD.

PMID- 16098561
TI  - Field investigation on the toxicity of Alaska North Slope crude oil (ANSC) and
      dispersed ANSC crude to Gulf killifish, Eastern oyster and white shrimp.
AB  - A field investigation was conducted on a Louisiana Spartina alterniflora
      shoreline to evaluate the toxic effects of crude oil (Alaska North Slope crude
      oil, ANSC) and dispersed oil (ANSC + dispersant Corexit 9,500) on three aquatic
      species indigenous to the Gulf of Mexico: Fundulus grandis (Gulf killifish),
      Crassostrea virginica (Eastern oyster), and Litopenaeus setiferus (white shrimp).
      Results indicated that total hydrocarbons concentration value in oiled treatments
      decreased rapidly in 3h and were below 1 ppm at 24h after initial treatment.
      Corexit 9,500 facilitated more ANSC fractions to dissolve and disperse into the
      water column. L. setiferus showed short-term sensitivity to the ANSC and ANSC +
      9,500 at 30 ppm. However, most test organisms (>83%) of each species survived
      well after 24h exposure to the treatments. Laboratory tests conducted concurrent
      with the field investigation indicated that concentrations of crude oil higher
      than 30 ppm were required for any significant toxic effect on the juvenile
      organisms tested.

PMID- 16098562
TI  - The balance between influenza- and RSV-specific CD4 T cells secreting IL-10 or
      IFNgamma in young and healthy-elderly subjects.
AB  - Respiratory syncytial virus (RSV) and influenza virus cause severe disease in
      elderly patients. The balance of pro- and anti-inflammatory cytokines may be
      critical in determining disease pathogenesis and outcome of infection. The
      frequencies of CD4 IL-10 (anti-inflammatory)- and CD4 and CD8 IFNgamma (pro
      inflammatory)-secreting memory T cells specific for either RSV or influenza were
      not significantly different between young and elderly groups, although the ratio
      of IL-10/IFNgamma was significantly reduced in the elderly RSV response. A
      similar trend was seen for influenza. IFNgamma-secreting CD4 T cells contributed
      significantly more to anti-RSV than anti-influenza responses in both groups.

PMID- 16098563
TI  - Microsatellite instability (MSI) increases with age in normal somatic cells.
AB  - Small pool PCR (SP-PCR) is a sensitive method for the detection and
      quantification of microsatellite instability (MSI) in somatic cells. Here we
      propose that mutant microsatellite fragments accumulate with age in normal
      somatic cells and that this increase in MSI can be quantified by SP-PCR. MSI at 6
      microsatellite loci was determined by SP-PCR in PBL DNA from 17 "normal" blood
      bank donors. These individuals varied in age from 20 to 67 y/o. MSI phenotypes
      were plotted against age in a regression analyses. A positive slope indicated a
      correlation between age and MSI phenotype (p=0.0006). The mean weighted average
      mutant frequencies across all loci for all individuals in the age groups (0.009
      for 20-30 y/o; 0.019 for 35-50 y/o; 0.034 for 60-70 y/o) were also significantly
      different from each other (p<0.01). A baseline for increases of MSI with age in
      human somatic cells was therefore begun and the effectiveness of SP-PCR to
      evaluate low, but significant, levels of MSI, established.

PMID- 16098564
TI  - Impact of medical waste incineration in the atmospheric PCDD/F levels of Porto,
      Portugal.
AB  - As a consequence of a monitoring program of a new municipal waste incinerator
      initiated in 1998, a large data-base of dioxin and furan concentrations in the
      atmosphere of the metropolitan area of Porto, in northern Portugal, has been
      collected. The existence of this data coincides with the shutdown in January 2001
      of two medical waste incinerators that were under operation in the inner city of
      Porto. Dioxin emissions from these facilities were measured indicating emissions
      100 to 1000 times larger than recent European Union directive limits. Data show
      that the shutdown of these two units had a clear effect on the improvement of air
      quality in the region that was observed either on the overall level of dioxins
      and furans or as in subtle alterations of the homolog pattern of these compounds
      in the atmosphere.

PMID- 16098565
TI  - Evaluation of the automated coagulation analyzer Sysmex CA-7000.
AB  - The Sysmex CA-7000 is a fully automated multiparameter hemostasis analyzer
      equipped with a photo-optical clot detection unit and a cap-piercing system. It
      is designed to perform coagulation tests as well as chromogenic and immunologic
      assays. It was evaluated in a coagulation laboratory of a university hospital
      with respect to its technical characteristics in the determination of routine
      coagulation (prothrombin time, activated partial thromboplastin time, fibrinogen
      and single coagulation factors), chromogenic (antithrombin, and anti-FXa
      activity) and immunologic assays (von Willebrand factor). The intra-assay and
      inter-assay coefficients of variation (CV) were below 5% for most parameters both
      in the normal and in the pathological range (exceptions: intra-assay CV=5.2% for
      the fibrinogen and 5.1% for antithrombin in the low range of concentrations; and
      inter-assay CV=5.7% and 7.2% for clotting factors V and VII levels in the normal
      ranges, and in the range from 6.1% to 7.8% for anti-FXa activity). No significant
      interference could be demonstrated with hemolytic and icteric samples as
      demonstrated by results similar to those obtained using a mechanical clot
      detection-based analyzer (STAR). No carryover was detected in alternating
      measurements of heparinized (1.0 IU/mL unfractionated heparin) and normal plasma
      samples. The results of the different coagulation, chromogenic and immunologic
      assays obtained with the CA-7000 analyzer were well correlated with those
      obtained on the STAR analyzer (r in the range from 0.885 to 0.990). Our results
      demonstrated that using the CA-7000 analyzer, routine coagulation testing can be
      performed with satisfactory precision and the same applied to more specialized
      and specific tests such as single factor activity or antigen concentration.

PMID- 16098566
TI  - Early identification of acute myocardial infarction by activated protein C-
      protein C inhibitor complex.
AB  - INTRODUCTION: Increased coagulation activity due to coronary thrombosis in a
      ruptured plaque should result in activation of the protein C anticoagulant system
      with formation of complexes between activated protein C (APC) and the protein C
      inhibitor (PCI), which reflects coagulation activity. We hypothesized that
      elevated APC-PCI concentration might allow earlier detection of ongoing
      myocardial infarction than traditional biochemical markers. We have evaluated a
      newly devised immunofluorimetric assay for measuring plasma concentration of APC
      PCI complexes among patients with suspected acute coronary syndrome. MATERIALS
      AND METHODS: Blood samples were taken from 340 patients (median 71 years, range
      31-97) with suspected acute coronary syndrome at first presentation in the
      emergency department. Electrocardiogram was recorded and APC-PCI, Troponin I and
      Creatine kinase-MB concentrations were repeatedly measured 3 times at 6 h
      interval. RESULTS: The 74 patients who were eventually diagnosed with myocardial
      infarction had a higher median level of APC-PCI complex than those without
      myocardial damage; 0.27 vs. 0.20 microg/L (p = 0.001). In a multivariate
      regression model, APC-PCI level in the fourth quartile (>0.32 microg/L)
      independently predicted myocardial infarction with an odds ratio of 3.7 (95% CI
      1.4-9.6, p < 0.01). CONCLUSION: Early APC-PCI elevation can be detected among
      patients with a normal first Troponin I and non-ST-elevation myocardial
      infarction and provides additional risk assessment in acute coronary syndrome.

PMID- 16098567
TI  - Similarities and differences in the thioredoxin superfamily.
AB  - There is growing interest in the proteins involved in protein folding. This is
      mainly due to the large number of human diseases related to defects in folding,
      which include cystic fibrosis, Alzheimer's and cancer. However, equally important
      as the oxidation and concomitant formation of disulfide bridges of the
      extracellular or secretory proteins is the reduction and maintenance in the
      reduced state of the proteins within the cell. Interestingly, the proteins that
      are responsible for maintenance of the reduced state belong to the same
      superfamily as those responsible for the formation of disulfide bridges: all are
      members of the thioredoxin superfamily. In this article, we highlight the main
      features of those thioredoxin-like proteins directly involved in the redox
      reactions. We describe their biological functions, cytoplasmic location,
      mechanisms of action, structures and active site features, and discuss the
      principal hypotheses concerning origins of the different reduction potentials and
      unusual pK(a)'s of the catalytic residues.

PMID- 16098568
TI  - Phase singularities and filaments: simplifying complexity in computational models
      of ventricular fibrillation.
AB  - In the whole heart, millions of cardiac cells are involved in ventricular
      fibrillation (VF). Experimental studies indicate that VF is sustained by re
      entrant activity, and that each re-entrant wave rotates around a filament of
      phase singularity. Filaments act as organising centres, and offer a way to
      simplify and quantify the complex spatio-temporal behaviour observed in VF. Where
      a filament touches the surface of fibrillating myocardium re-entrant activity can
      be observed, however the behaviour of filaments within bulk ventricular
      myocardium is difficult to observe directly using present experimental
      techniques. Large scale computational simulations of VF in three-dimensional (3D)
      tissue offer a tool to investigate the properties and behaviour of filaments, and
      the aim of this paper is to review recent advances in this area as well as to
      compare recent computational studies of fibrillation in whole ventricle
      geometries.

PMID- 16098569
TI  - Ondansetron, dexamethasone and an NK1 antagonist block radiation sickness in
      mice.
AB  - Radiation sickness is frequently observed in total body irradiation (TBI). We
      have reported that the kaolin ingestion behavior "pica" may be analogous to
      nausea and vomiting in mice. We evaluated the effects of anti-emetics on the
      prevention of radiation-induced pica in mice. After the intraperitoneal injection
      of ondansetron (OND: 2 mg/kg), dexamethasone (DEX: 2 mg/kg) or CP-99,994 (CP: 15
      mg/kg), mice received 9 Gy of TBI, and then kaolin consumption was measured after
      24 h. Radiation-induced pica was slightly inhibited by pretreatment with a single
      administration of OND or DEX, but not by CP (control: 0.69+/-0.19 g, OND: 0.33+/
      0.06 g, DEX: 0.39+/-0.07 g, CP: 0.66+/-0.09 g); it was significantly inhibited by
      the combination treatment of OND and DEX (control: 0.55+/-0.09 g, OND+DEX: 0.30+/
      0.06 g, OND+CP: 0.70+/-0.04 g, DEX+CP: 0.58+/-0.02 g). The combination of the
      three drugs completely abolished the behavior (control: 0.67+/-0.08 g,
      OND+DEX+CP: 0.10+/-0.05 g). These results suggest that radiation-induced pica in
      mice may be useful to evaluate drugs for treatment of radiation sickness and that
      the combination therapy of a serotonin 5-HT3 receptor antagonist and a
      glucocorticosteroid with a neurokinin NK1 receptor antagonist is effective in
      reducing the symptom.

PMID- 16098570
TI  - Perinatal maternal exposure to picrotoxin: effects on sexual behavior in female
      rat offspring.
AB  - A previous study in our laboratory showed that perinatal maternal picrotoxin
      exposure (0.75 mg/kg) in rats improved heterosexual behavior in male offspring.
      In the present study, we examined the effects of this maternal treatment on
      sexual behavior in the female offspring. The dams received 0.75 mg/kg picrotoxin
      treatment (PT) once a day on the 18th and 21st day of pregnancy, 2 h after
      parturition and once a day during the first 4 days of lactation. The results
      showed that (1) at birth, the body weight and anogenital distance were not
      modified by treatment; (2) female sexual behavior was improved in experimental
      animals. These results demonstrate that perinatal picrotoxin exposure improves
      adult sexual behavior in female rat offspring as suggested by increase in the
      lordosis quotient.

PMID- 16098571
TI  - Differential prefrontal-temporal neural correlates of semantic processing in
      children.
AB  - This study used functional magnetic resonance imaging (fMRI) to examine brain
      behavior correlations in a group of 16 children (9- to 12-year-olds). Activation
      was measured during a semantic judgment task presented in either the visual or
      auditory modality that required the individual to determine whether a final word
      was related in meaning to one of two previous words (e.g., found-tank-lost). The
      main finding was that higher performers (i.e., accuracy) were associated with
      more activation in posterior representational systems including the inferior and
      middle temporal gyri, whereas lower performers were associated with more
      activation in anterior regions including the inferior and middle frontal gyri.
      This pattern of results was interpreted as reflecting an elaborated semantic
      representational system in temporal areas for the high accuracy performers that
      allowed them to efficiently and accurately make meaning based judgments. The low
      accuracy performers may have an inaccurate or weakly interconnected semantic
      system that results in greater use of frontal areas in a feature selection
      process.

PMID- 16098572
TI  - Molecular regulation of milk trace mineral homeostasis.
AB  - The regulation of milk trace mineral homeostasis requires the temporal
      integration of three main processes, (A) mineral uptake into the secretory
      mammary epithelial cell (MEC); followed by (B) mineral secretion from MEC into
      the alveoli lumen of the mammary gland for sequestration in milk; and then (C)
      milk release in response to suckling. Trace mineral requirements of term infants
      are generally met by exclusive breast-feeding through about the first 6 months of
      life and although milk zinc (Zn), iron (Fe), and copper (Cu) concentrations are
      relatively refractory to maternal trace mineral status, they normally decline
      throughout lactation. Recently, Zn-, Fe- and Cu-specific transporters have been
      identified that regulate trace element uptake and efflux in various cell types;
      however, there is currently little information available regarding the processes
      through which the mammary gland regulates milk trace mineral transport. The
      homology of trace mineral transporters between species permits the utilization of
      rodent models to examine the regulation of mammary gland mineral transport.
      Therefore, we have used the lactating rat to determine changes in mammary gland
      Zn, Fe and Cu transporter expression and localization that occur throughout
      lactation and in response to maternal trace mineral deficiency in hope of
      elucidating some of the changes which occur during mammary gland trace element
      homeostasis and also may be occurring in lactating women.

PMID- 16098573
TI  - A physico-chemical explanation of the post-polymerization shrinkage in dental
      resins.
AB  - The main problem of a methacrylated dental resin's photopolymerization is the
      shrinkage phenomenon. This occurs, as expected, during light irradiation but
      also, unexpectedly, during about 24h after photopolymerization (i.e. during the
      so-called 'post-polymerization' stage). During this period, the conversion degree
      does not change significantly (no more initiation, very limited, if any,
      propagation reaction) but free radicals concentration decreases. OBJECTIVES: To
      better understand what happens during the 24h after the photopolymerization, a
      thermal study of these resins is investigated at first and an explanation is then
      discussed. METHODS: In this paper, the glass transition temperatures (T(g)) are
      measured at 0 and 24h by DMA. The post-shrinkage phenomenon is observed by TMA.
      Conversion degree (DC) is followed by Raman and free radical decay by ESR
      spectroscopy. RESULTS: T(g) increases significantly during post-polymerization
      (55-80 degrees C). The same samples were studied by TMA at room temperature and
      shrinkage is observed. The fact that the degree of conversion (DC) does not
      increase significantly and that the 'post-shrinkage' occurs at T<T(g) leads to
      the hypothesis that a physical phenomenon should occur which can, in turn, be
      responsible for a secondary chemical phenomenon (post-polymerization).
      SIGNIFICANCE: The proposed explanation is that, as photopolymerization of dental
      resins is very fast, a large excess of free volume is trapped in non-equilibrated
      samples. As they have no time to return to an equilibrium state, free volume
      should decrease below T(g) and samples do physically shrink during the first 24h.
      As a consequence, free radicals can come into 'contact' and undergo limited
      propagation but significant termination justifying the decrease in overall
      radical concentration.

PMID- 16098574
TI  - Influence of tooth preparation design on the stress distribution in maxillary
      central incisors restored by means of alumina porcelain veneers: a 3D-finite
      element analysis.
AB  - AIM: The present study aimed at providing 3D-FEA engineering tools for the
      understanding of the influence of tooth preparation design on the stress
      distribution and localization of critical sites in maxillary central incisors
      restored by means of alumina porcelain veneers under functional loading. METHODS:
      A 3D-FEM model of a maxillary central incisor is presented. An arbitrary chewing
      static force of 10 N was applied with an angulation of 60 and 125 degrees to the
      tooth longitudinal axis at the palatal surface of the crown. The model was
      considered to be restored by means of alumina porcelain veneers with different
      tooth preparation designs. The differences in occlusal load transfer ability of
      the two restorative systems are discussed. RESULTS: The maximum Von Mises
      equivalent stress values were observed in the window restorative system for both
      125 and 60 degrees load angulations. When the chamfer with palatal overlap
      preparation was simulated, the stress distributed uniformly in the cement layer,
      whereas in the window preparation the stress mainly occurred in the incisal area
      of the cement layer. SIGNIFICANCE: When restoring a tooth by means of porcelain
      veneers, the chamfer with palatal overlap preparation better restores the natural
      stress distribution under load than the window technique.

PMID- 16098575
TI  - Effect of the composite photoactivation mode on microtensile bond strength and
      Knoop microhardness.
AB  - OBJECTIVE: This study evaluated the effect of the composite photoactivation mode
      on microtensile bond strength and Knoop microhardness. METHODS: Standard class I
      cavities (3 x 4 x 3mm) were restored with two adhesives systems, Single Bond (SB)
      and Clearfil SE Bond (CE), and the TPH composite. The photoactivation of the
      composite was carried out using three modes: Conventional (CO: 400 mW/cm(2) x
      40s), Soft-Start (SS: 100 mW/cm(2) x 10s+600 mW/cm(2) x 30s) and Pulse-Delay (PD:
      100 mW/cm(2) x 3s+3 min wait+600 mW/cm(2) x 37s). For the microtensile test,
      beams obtained from the buccal wall bond interface were tested under tension at
      0.5mm/min crosshead speed until failure. For the microhardness test, the
      restorations were sectioned in the mesio-distal direction and indentations were
      made on the internal composite surface of each half at three different depths.
      Data of two tests were analyzed using two-way ANOVA and LSMeans (alpha=0.05).
      RESULTS: In the microtensile test, SS presented the highest values. PD presented
      intermediate values without differing significantly from the other modes. For
      adhesives, SB presented the highest values. In the microhardness test, PD
      presented the highest values, differing significantly from SS. CO presented
      intermediate values but without any statistical difference from the others. The
      SS-CE interaction presented the lowest values with statistical differences from
      all the others. SIGNIFICANCE: By the SS technique, the highest bond strength was
      obtained. However, this technique made it possible for the adhesive system to
      intervene with the hardness of the composite.

PMID- 16098576
TI  - A modeling study of alphaB-crystallin in complex with zinc for seeking of
      correlations between chaperone-like activity and exposure of hydrophobic
      surfaces.
AB  - Three-dimensional models for alphaB-crystallin and its complex with zinc were
      obtained by molecular homology modeling and quantum mechanical calculations in
      order to explain the effect of the metal on the chaperone-like activity of alphaB
      crystallin. In fact, measurements of the chaperone-like activity of alphaB
      crystallin revealed that it is significantly increased in presence of the zinc.
      The theoretical models allowed us to estimate the increased exposition of
      hydrophobic residues caused by the presence of zinc, suggesting a relationship
      between structural changes and the increased chaperone-like activity.

PMID- 16098577
TI  - Synthesis and characterization of novel aromatic azo bond-containing pH-sensitive
      and hydrolytically cleavable IPN hydrogels.
AB  - Novel interpenetrating network (IPN) hydrogels, composed of pH-sensitive,
      aromatic azo group containing network as one component (Network A), and a
      hydrolyzable network as the other (Network B), were prepared by a sequential
      process. The first network was formed by crosslinking of a reactive polymer
      precursor (copolymer of N,N-dimethylacrylamide, acrylic acid, N
      tert.butylacrylamide, and N-methacryloylglycylglycine p-nitrophenyl ester) with
      an aromatic azo group containing diamine ((N,N'-epsilon-aminocaproyl)-4,4'
      diaminoazobenzene). The second network was formed by radical crosslinking
      copolymerization of N-(2-hydroxypropyl)methacrylamide with N,O
      dimethacryloylhydroxylamine. The composition of the hydrogels was manipulated to
      determine the influence of hydrogel composition on the equilibrium degree of
      swelling, modulus of elasticity in compression, and on the rate of degradation of
      Network B. Modeling of network structure was accomplished using the statistical
      branching theory. The major advantage of IPN hydrogels, when compared to
      traditional pH-sensitive networks, is the linear swelling profile following
      abrupt change of pH from 2 to 7.4. This indicates the suitability of IPN as
      carriers for oral drug delivery.

PMID- 16098578
TI  - Interaction of B50 rat hippocampal cells with stain-etched porous silicon.
AB  - We present a scanning electron microscopy study of interaction of porous silicon
      prepared by stain etching with rat hippocampal neurons (B50, immortalised line).
      Porous Si has been prepared by stain etching both from crystalline and
      polycrystalline substrates. Two types of patterns have been examined: (i) 100
      microm square pads separated by 100 microm of untreated space and (ii) 30 microm
      and 100 microm stripes separated by 300 microm of untreated surface. In all cases
      cells show clear preference in adhesion to porous Si over untreated surface. We
      observe a much closer attachment of the cell to the surface of porous Si than has
      been anticipated before with the gap between a cell and porous surface of no more
      than 20 nm. This study demonstrates the influence of surface topology on
      proliferation of a neuron network, thus suggesting that a degree of control over
      cell growth pattern can be achieved using porous material alone. We show that the
      network pattern on porous Si is influenced by a single neuron response to the
      surface nature and topology.

PMID- 16098579
TI  - Improved surgical mesh integration into the rat abdominal wall with arginine
      administration.
AB  - Prosthetic meshes are used as the standard of care in abdominal wall hernia
      repair. However, hernia recurrences and side effects remain unsolved problems.
      The demand by health care providers for increasingly efficient and cost-effective
      surgery encourages the development of newer strategies to improve devices and
      outcomes. Here, we evaluated whether l-arginine administration was able to
      ameliorate long-term polypropylene prostheses incorporation into the abdominal
      wall of Sprague-Dawley rats. Meshes were placed on-lay and continuous l-arginine
      was administered. In vivo biocompatibility was studied at 7, 25 and 30 days post
      implantation. Effectively, l-arginine administration in combination with mesh
      triggered subtle changes in ECM composition that impinged on critical biochemical
      and structural features. Lastly, tensile strength augmented and stiffness
      decreased over the control condition. This could help to restructure the
      mechanical load transfer from the implant to the brittle surrounding tissues,
      i.e., impact load and fatigue load associated with mechanical tensions could be
      distributed between the mesh and the restored tissue in a more balanced manner,
      and ultimately help to reduce the incidence of loosening, recurrences, and local
      wound complications. Since the newly formed tissue is more mechanically stable,
      this approach could eventually be introduced to human hernia repair.

PMID- 16098580
TI  - A "room-temperature" injection molding/particulate leaching approach for
      fabrication of biodegradable three-dimensional porous scaffolds.
AB  - A "room-temperature" injection molding approach combined with particulate
      leaching (RTIM/PL) has been, for the first time, developed in this work to
      fabricate three-dimensional porous scaffolds composed of biodegradable polyesters
      for tissue engineering. In this approach, a "wet" composite of
      particulate/polymer/solvent was used in processing, and thus the injection was
      not performed at melting state. Appropriate viscosity and flowability were
      facilely obtained at a certain solvent content so that the composite was able to
      be injected into a mould under low pressure at room temperature, which was very
      beneficial for avoiding thermal degradation of polyesters. As a demonstration,
      tubular and ear-shaped porous scaffolds were fabricated from biodegradable
      poly(D,L-lactide-co-glycolide) (PLGA) by this technology. Porosities of the
      resulting scaffolds were as high as 94%. The pores were well interconnected.
      Besides the well-known characteristics of injection molding to be suitable for
      automatization of a fabrication process with high repeatability and precision,
      this RTIM/PL approach is much suitable for tailoring highly porous foams with its
      advantages flexible for shaping complicated scaffolds, free of thermal
      degradation and high-pressure machine, etc.

PMID- 16098581
TI  - Three-dimensional culture of human disc cells within agarose or a collagen
      sponge: assessment of proteoglycan production.
AB  - The objective of the present study was to assess proteoglycan production by human
      intervertebral disc cells cultured in vitro in selected cell carriers. Based on
      previous studies which evaluated disc cells seeded into collagen sponge, collagen
      gel, agarose, alginate or fibrin gel three-dimensional (3D) cell carriers,
      collagen sponge and agarose were found to provide superior microenvironments for
      formation of extracellular matrix (ECM). A standardized test design was used to
      evaluate ECM formed after 14 days of culture using the 1,9-dimethylmethylene blue
      (DMB) assay to assess sulfated glycosaminoglycan (S-GAG) production. Although
      agarose culture showed higher S-GAG levels compared to collagen sponge (2.94+/
      2.20 (19) microg/ml S-GAG (mean+/-S.D. (n)) vs. 0.94+/-0.77 (22), respectively,
      p=0.0003), this is off-set by the significantly lower proliferation rate
      associated with culture of disc cells in agarose.

PMID- 16098582
TI  - The effect of high outflow permeability in asymmetric poly(dl-lactic acid-co
      glycolic acid) conduits for peripheral nerve regeneration.
AB  - This study attempted to accelerate the peripheral nerve regeneration, using the
      high outflow rate of asymmetric poly(dl-lactic acid-co-glycolic acid) (PLGA)
      nerve conduits. Asymmetric PLGA nerve conduits of monomer ratio 85/15 were
      prepared by immersion-precipitation method to serve as possible materials. In
      this study, mandrels were immersed into a 20% (wt/wt) of PLGA/1,4-dioxane
      solution and precipitated in a non-solvent bath followed by freeze-drying.
      Different concentrations of isopropyl alcohol (95%, 40% and 20%) were used as
      precipitation baths where non-asymmetric (95%) and asymmetric (40% and 20%)
      conduits could easily form. The asymmetric nerve conduits that consisted of
      macrovoids on the outer layer, and interconnected micropores in the inner
      sublayer, possessed characters of larger outflow rate than inflow rate. The
      asymmetric conduits were implanted to 10mm right sciatic nerve defects in rats.
      Autografts, silicone and non-asymmetric PLGA conduits were performed as the
      control and the contrast groups. Implanted graft specimens of all groups were
      harvested for histological analysis at 4 and 6 weeks following surgery. The
      asymmetric PLGA conduits maintained a stable supporting structure and inhibited
      exogenous cells invasion during entire regeneration process. Asymmetric PLGA
      conduits were found to have statistically greater number of regenerated axons at
      the midconduit and distal nerve site of implanted grafts, as compared to the
      silicone and non-asymmetric groups at 4 and 6 weeks. Of interest was that the
      results of 4 weeks in asymmetric groups were better than the non-asymmetric
      groups at 6 weeks in number of axons. According to the results of permeability,
      the asymmetric structure in the conduit wall seemed to enhance the removal of the
      blockage of the waste drain from the inner inflamed wound in the early stage,
      which may have improved the efficacy of the peripheral nerve regeneration. The
      asymmetric structure could be adequately employed in the future as optimal nerve
      conduits in peripheral nerve regeneration.

PMID- 16098583
TI  - The use of a bioresorbable nano-crystalline hydroxyapatite paste in acetabular
      bone impaction grafting.
AB  - Calcium phosphates such as TCP-HA granules are considered promising bone graft
      substitutes. In the future, they may completely replace allograft bone for
      impaction grafting procedures. Mechanically, acetabular reconstructions with TCP
      HA granules show high stability, however this is partly caused by excessive
      cement penetration, which is unfavourable from a biological perspective. It has
      been hypothesised that mixtures of morselised cancellous bone grafts (MCB) and/or
      TCP-HA granules with a nano-crystalline hydroxyapatite paste (Ostim) may reduce
      cement penetration while maintaining adequate implant stability and
      biocompatibility of the graft mixture. To investigate this hypothesis,
      destructive lever-out tests and in vivo animal test were performed with various
      combinations of materials. Mechanically, the addition of 10% Ostim to mixtures of
      MCB and/or TCP-HA granules reduced cement penetration and resulted in a
      mechanical stability comparable to pure allograft (the current gold standard).
      Biologically, the application of Ostim with MCB or TCP-HA granules did not hamper
      the biocompatibility of the materials. Ostim was mostly osseous-integrated with
      MCB or TCP-HA granules after 8 weeks. Also, non-osseous-integrated Ostim remnants
      were observed. In tartrate resistant acid phosphatase stained sections, these few
      non-osseous integrated Ostim remnants were actively being resorbed by
      osteoclasts. In conclusion, Ostim HA-paste could be a valuable addition when TCP
      HA ceramic granules are being used for acetabular bone impaction grafting
      procedures.

PMID- 16098584
TI  - Calcium channel inactivation: possible role in signal transduction and Ca2+
      signaling.
AB  - Voltage gated Ca2+ channels are major routes for the entry of intracellular Ca2+
      coupled to membrane depolarization that appear to vary greatly with respect to
      their voltage dependence and kinetics. Such variability maybe in part related to
      the attached signaling properties of the channel, in addition to the transport of
      calcium. In the present review we consider the possible role of calcium-dependent
      inactivation of Cav1.2 in Ca2+ signal transduction and signaling of calcium
      release from the cardiac sarcoplasmic reticulum. We explore the specific roles of
      Ca2+-sensing calmodulin-binding domains of the C-terminal tail (LA and K) of the
      channel in mediating Ca2+-induced Ca2+ release and signal transduction. Our
      experiments point to an intriguing possibility that the C-terminal tail of Cav1.2
      may translocate the Ca2+ signal as a part of inactivation mechanism and the
      corresponding voltage-gated rearrangement of the C-terminus. We show how a
      dynamic and transient regulation, in a Ca2+-dependent manner, defines molecular
      events including Ca2+ release and signaling of cAMP-responsive element-binding
      protein (CREB)-dependent transcription. We propose that such Ca2+-dependent C
      tail translocation that also initiates the channel inactivation, may have evolved
      specifically for the Cav1.2 channel.

PMID- 16098585
TI  - TRP channels: an overview.
AB  - The TRP ("transient receptor potential") family of ion channels now comprises
      more than 30 cation channels, most of which are permeable for Ca2+, and some also
      for Mg2+. On the basis of sequence homology, the TRP family can be divided in
      seven main subfamilies: the TRPC ('Canonical') family, the TRPV ('Vanilloid')
      family, the TRPM ('Melastatin') family, the TRPP ('Polycystin') family, the TRPML
      ('Mucolipin') family, the TRPA ('Ankyrin') family, and the TRPN ('NOMPC') family.
      The cloning and characterization of members of this cation channel family has
      exploded during recent years, leading to a plethora of data on the roles of TRPs
      in a variety of tissues and species, including mammals, insects, and yeast. The
      present review summarizes the most pertinent recent evidence regarding the
      structural and functional properties of TRP channels, focusing on the regulation
      and physiology of mammalian TRPs.

PMID- 16098586
TI  - ERK expands its empire.

PMID- 16098587
TI  - CD34/CD117 positivity in assessment of prognosis in children with myelodysplastic
      syndrome.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell
      disorders that are characterized by morphology identifying dysplastic changes in
      one or more cell lineages, peripheral blood cytopenias and a propensity to evolve
      into secondary acute myeloid leukemia (AML). CD34 is commonly expressed in all
      types of childhood leukemias, whereas CD117 is a reliable and specific marker to
      detect leukemia cells committed to myeloid lineage. Co-expression of CD34/CD117
      may strongly suggest the diagnosis of AML (Rytting ME. Pediatric myelodysplastic
      syndromes. Curr hematol Rep 2004;3(3):173-7. May; Uckan D, Hicsonmez G, Yetgin S,
      Gurgey A, Cetin M, Karaagaoglu E, et al. CD34/CD117 co-expression in childhood
      acute leukemia. Leukemia Res 2000;24:201-6.). We describe the case of a 22 month
      old-girl with MDS and Down syndrome who was presented with severe anemia and
      thrombocytosis at diagnosis, transformed into AML-M7. In our patient, CD34 and
      CD117 markers were positive on the blast cells of the BM 6 months before the
      chemotherapy decision. As the disease progressed, CD34/117 co-existence was
      increased and MDS transformed into AML. As a result, an increase in CD34 and
      CD117 positivity of the BM blast cells may be associated with a higher risk of
      leukemic transformation.

PMID- 16098588
TI  - B cell and antibody repertoire development in rabbits: the requirement of gut
      associated lymphoid tissues.
AB  - The antibody repertoire of rabbits has interested immunologists for decades, in
      part because of the ease with which large quantities of high affinity antibodies
      can be obtained in serum, and in part because of the presence of genetic
      variants, allotypes, within V(H), C(H) and C(L) regions. Studies of these
      allotypes led to the initial descriptions of allelic exclusion, and neonatal
      suppression of serum Ig production (allotype suppression), and were instrumental
      in demonstrating that V and C regions are encoded by separate genes and are
      usually expressed in cis. The immune system of rabbit continues to be of interest
      primarily because of the use of both gene conversion and somatic hypermutation to
      diversify rearranged heavy and light chain genes and the role that gut-associated
      lymphoid tissues (GALT) and intestinal flora play in developing the primary
      (preimmune) antibody repertoire.

PMID- 16098589
TI  - Acute toxicities of four metals on the early life stages of the crab
      Chasmagnathus granulata from Bahia Blanca estuary, Argentina.
AB  - Acute semistatic toxicity tests were carried out for 96 h with first zoeae and
      young crabs of Chasmagnathus granulata. Survival curves and LC50 (lethal
      concentration 50, the concentration which produces the death of 50% of the
      exposed population) indices for copper, zinc, cadmium, and lead were determined.
      Furthermore, mixture toxicity tests (Cd/Cu and Cd/Zn) with first-stage larvae
      were also carried out. The LC50-96 h values determined in this study were 1093.4
      (881-1319) microg Pb2+ L(-1), 219.2 (188.9-248.9) microg Cu2+ L(-1), 172.1 (141.3
      203.6) microg Zn2+ L(-1), and 47.8 (37.9-58.0) microg Cd2+ L(-1) for zoeae I and
      130.1 (121.7-139.0) mg Cu2+ L(-1), 51.0 (41.9-61.6) mg Zn2+ L(-1), and 35.7 (30.1
      41.9) mg Cd2+ L(-1) for young crabs. The LC50-96 h indices for mixture tests with
      zoeae I were 260.6 (227.3-286.3) microg Cd2+/Zn2+ L(-1) and 41.3 (37.4-60.7)
      microg Cd2+/Cu2+ L(-1). Cadmium presented the highest acute toxicity for both
      stages of the life cycle examined. The toxicity of the metals analyzed followed
      the order cadmium >zinc>copper>lead. First zoeae were more sensitive than young
      crabs to acute exposure to all metals analyzed. The young crabs were considered
      potentially dangerous agents of transference to the associated trophic chain
      because of their relatively elevated resistance and their capacity to
      bioaccumulate heavy metals in their tissues. Mixed toxicity tests carried out on
      first-stage larvae showed different kinds of interactions. Cadmium/copper
      presented an additive interaction trend while the mixture cadmium/zinc showed an
      antagonistic interaction.

PMID- 16098590
TI  - Scientific coats of arms.
AB  - With their mythical creatures and arcane symbolism, coats of arms seem to have
      little connection with modern science. Yet despite its chivalric origins, the
      ancient language of heraldry has long fascinated famous scientists. Although this
      idiosyncratic tradition was parodied by Victorian geologists, who laughingly
      replaced unicorns and griffins with images of dinosaurs that they had recently
      discovered, it has been perpetuated since by Ernest Rutherford, who liked to
      present himself as a new alchemist.

PMID- 16098591
TI  - The descent of words: evolutionary thinking 1780-1880.
AB  - Histories of evolutionary thought are dominated by organic evolution. The
      colossus in our midst that is evolutionary biology casts its shadow over history,
      making it appear that what is so widespread and important today was always the
      primary subject of evolutionary speculation. Thus many histories assume that the
      core meaning of evolution is the change of organic life and that other forms of
      evolutionary thinking, such as linguistic, social or cultural evolution, are only
      analogies or offshoots of the main biological evolutionary trunk. Ironically this
      is an ahistorical understanding. Long before the work of Charles Darwin, scholars
      were independently developing evolutionary concepts such as descent with
      modification and divergence from a common stock in order to understand cultural
      change.

PMID- 16098592
TI  - Human cytomegalovirus-encoded US2 and US11 target unassembled MHC class I heavy
      chains for degradation.
AB  - Surface MHC class I molecules serve important immune functions as ligands for
      both T and NK cell receptors for the elimination of infected and malignant cells.
      In order to reach the cell surface, MHC class I molecules have to fold properly
      and form trimers consisting of a heavy chain (HC), a beta2-microglobulin light
      chain and an 8-10-mer peptide. A panel of ER chaperones facilitates the folding
      and assembly process. Incorrectly assembled or folded MHC class I HCs are
      detected by the ER quality-control system and transported to the cytosol for
      degradation by proteasomes. In human cytomegalovirus-infected cells, two viral
      proteins are synthesized, US2 and US11, which target MHC class I HCs for
      proteasomal degradation. It is unknown at which stage of MHC class I folding and
      complex formation US2 and US11 come into play. In addition, it is unclear if the
      disposal takes place via the same pathway through which proteins are removed that
      fail to pass ER quality control. In this study, we show with a beta2m-deficient
      cell line that US2 and US11 both target unassembled HCs for degradation. This
      suggests that US2 and US11 both act at an early stage of MHC class I complex
      formation. In addition, our data indicate that US11-mediated degradation involves
      mechanisms that are similar to those normally used to remove terminally misfolded
      HCs.

PMID- 16098593
TI  - Profile of Toll-like receptor expressions and induction of nitric oxide synthesis
      by Toll-like receptor agonists in chicken monocytes.
AB  - Toll-like receptors (TLRs) play a major role in the innate immune system for
      initial recognition of microbial pathogens and pathogen associated components.
      Nitric oxide (NO) is generated in immune cells in response to microbial
      stimulation and is involved in pathogenesis and control of infection. We used RT
      PCR analysis to examine the TLR expression profile on chicken monocytes and
      demonstrated these cells express chicken TLR2, 3, 4, 6, and 7. TLR5 was not
      detected by the TR-PCR. We also investigated the differential induction of NO
      synthesis in chicken monocytes by TLR agonists, including flagellin (FGN, from
      Salmonella typhimurium), synthetic lipoprotein Pam3CSK4 (PAM), lipopolysaccharide
      (LPS, from Salmonella enteritidis), lipoteichoic acid (LTA, from Staphylococcus
      aureus), the synthetic double stranded RNA analog (poly I:C), the guanosine
      analog, loxoribine (LOX), and synthetic CpG oligodeoxydinucleotide (CpG-ODN). Our
      results indicate that there was a vast difference among these agonists for their
      ability to induce NO production. CpG-ODN and LPS were the most potent stimuli and
      induced significant quantities of NO in cultured monocytes, whereas LTA
      stimulated significant NO production only at high concentrations. Other agonists
      such as FGN and poly I:C stimulated very little NO, while PAM, LOX, and nCpG-ODN
      (control ODN) did not induce NO production. RT-PCR analysis demonstrated that
      LPS, LTA, and CpG-ODN induced inducible nitric oxide synthase (iNOS) expression
      in monocytes; whereas the other agonists did not. The presence of TLRs on chicken
      monocytes and the differential induction of NO production in chicken monocytes by
      various TLR agonists suggest the differentiation of signaling pathways downstream
      of individual TLRs.

PMID- 16098594
TI  - A G protein-associated ERK pathway is involved in LPS-induced proliferation and a
      PTK-associated p38 MAPK pathway is involved in LPS-induced differentiation in
      resting B cells.
AB  - We, previously, showed that PKC-dependent ERK/p38 MAPK activation was inhibited
      by treating the resting B cell line 38B9 with an anti-MHC class II antibody.
      Further studies in this work demonstrated that PKA was involved in
      lipopolysaccharide (LPS)-induced proliferation of the cells, such that the PKC
      inhibitor activated PKA with concomitant LPS-induced proliferation but not IgG
      secretion. Consequently, the PKA inhibitor down-regulated ERK and p38 MAPK, and
      decreased cell proliferation. In addition, the treatment of LPS-stimulated 38B9
      cells with PTK inhibitor reduced PKC- and PKA-dependent p38 MAPK activation and
      reduced the level of IgG secretion rather than the level of proliferation.
      However, the treatment of LPS-stimulated 38B9 cells with pertussis toxin (PTX),
      an inhibitor for the G protein-coupled receptor, inhibited the activation of both
      PKC- and PKA-dependent ERK and significantly reduced LPS-induced proliferation
      but not IgG secretion. Furthermore, ERK and p38 MAPK inhibitors reduced LPS
      induced proliferation and differentiation, respectively, in 38B9 cells in a dose
      dependent manner. These results suggest that LPS-induced proliferation of resting
      B cells is mainly mediated through a G protein-associated PKA/PKC-dependent ERK
      pathway and that a PTK-associated PKC/PKA-dependent p38 MAPK pathway is mostly
      involved in LPS-induced differentiation of the resting B cells.

PMID- 16098595
TI  - Structural comparison of human C4A3 and C4B1 after proteolytic activation by C1s.
AB  - The fourth component of human complement is an essential part of the classical
      and lectin pathways performing multifunctional roles in both host defense and
      immune regulation. C4 is the most polymorphic member of the complement proteins,
      and complete deficiency is strongly associated with autoimmune disease,
      especially, systemic lupus erythematosus (SLE). Of the two C4 genes C4A, but not
      C4B, null alleles have been implicated as important independent disease
      susceptibility genes occurring in more than half of SLE patients. Whether and how
      this deficiency contributes to the development or pathology remains unclear. We
      do know that activation of C4 by C1s cleaves the thioester bond, thus inducing a
      conformational change that exposes numerous ligand-binding sites involved in
      functional activity. Structural comparison, among many other tools, plays an
      important role in predicting function. In this report, the tertiary structures of
      C4A and C4B were compared using near and far-UV circular dichroism, ANS
      fluorescence, site-specific monoclonal antibodies and isoelectric focusing.
      Negligible differences in the native proteins were found. However, the activated
      proteins were dissimilar in secondary and tertiary structure that was accompanied
      by significant differences in charge distribution and surface hydrophobicity.
      These conformational differences, together with known acceptor preferences, have
      functional implications for the association between C4A null alleles and SLE.

PMID- 16098596
TI  - Chelating effect of novel pyrimidines in a model of aluminum intoxication.
AB  - Long time ago aluminum (Al) was considered as a non-toxic element and its use had
      no restrictions. However, over the last two decades, scientific publications have
      indicated that Al is a toxic element. In line with this, aluminum accumulation in
      the organism is associated with a variety of human pathologies. Efficient
      therapeutics approach to treat Al intoxication are still not available, but there
      is a consensus that chelation therapy is the procedure to be used. However, the
      development of new chelating agents are highly desirable to improve the efficacy
      of the treatment of Al intoxication. The present study evaluates the chelating
      effect of two novel pyrimidines: 4-tricloromethyl-1-H-pyrimidin-2-one (THP) and
      (4-methyl-6-trifluoromethyl-6-pyrimidin-2-il)-hydrazine (MTPH) in a mice model of
      aluminum intoxication and compares their efficacy with those of desferrioxamine
      (DFO), a classical agent used for treat Al accumulation. The animals were exposed
      to aluminum by gavage (0.1 mmol aluminum/kg/day) 5 days/week for 4 weeks. At the
      end of this period, DFO was injected i.p. and the novel pyrimidines were given by
      gavage at 0.2 mmol/kg/day for five consecutive days. Aluminum concentration in
      tissues (brain, liver, kidney and blood) was determined by graphite furnace
      atomic absorption spectroscopy (GFAAS). The results showed that when administered
      by gavage, aluminum accumulated in the brain, kidney and liver of mice. MTPH was
      able to decrease aluminum levels in aluminum plus citrate animal groups, whereas
      THP was inefficient for this purpose. However, the novel pyrimidines used in this
      study were unable to surpass the aluminum chelating property of DFO. Thus, new
      studies must be performed utilizing other chelating agents which can decrease
      aluminum toxicity.

PMID- 16098597
TI  - Drugs and alcohol: treating and preventing abuse, addiction and their medical
      consequences.
AB  - Recent advances in the fields of genetics, molecular biology, behavioral
      neuropharmacology, and brain imaging have dramatically changed our understanding
      of the addictive process and why relapse occurs even in the face of catastrophic
      consequences. Addiction is now recognized as a chronic brain disease that
      involves complex interactions between repeated exposure to drugs, biological
      (i.e., genetic and developmental), and environmental (i.e., drug availability,
      social, and economic variables) factors. Its treatment, therefore, requires, in
      general, not only a long-term intervention but also a multipronged approach that
      addresses the psychiatric, medical, legal, and social consequences of addiction.
      Also, because addiction usually starts in adolescence or early adulthood and is
      frequently comorbid with mental illness, we need to expand our treatment
      interventions in this age group both for substance abuse and psychiatric
      disorders.

PMID- 16098598
TI  - Drug-induced delayed cardiac protection against the effects of myocardial
      ischemia.
AB  - Drug-induced delayed cardiac protection (DCP) against the effects of acute
      myocardial ischemia was first described 22 years ago by the author and his
      coworkers. It can be initiated by noninjurious pharmacological doses of
      prostacyclin (PGI2), its stable analogues, and by catecholamines. DCP protects
      against many consequences of ischemia, attenuating early morphological changes,
      limiting infarct size and suppressing arrhythmias, and can also protect against
      ouabain intoxication. DCP operates under a variety of pathological conditions
      (atherosclerosis, hypercholesterolaemia, and diabetes). DCP can also be evoked by
      transient myocardial ischemia and by exercise and is known in this context as
      "ischemic preconditioning", specifically the "second window of protection";
      transient ischemia also evokes an immediate but short-lived protection known as
      "classical preconditioning". DCP is fundamentally different in concept to
      conventional drug therapy because the process appears to depend on the duration
      of the trigger and be related in a bell-shaped manner to the strength of the
      trigger. The exact mechanism is uncertain. Prolongation of the effective
      refractory period (ERP) and of the action potential duration (APD) may contribute
      to DCP suppression of arrhythmias. The protection is time and dose dependent,
      with optimal effects 24 to 48 hr after treatment. It can be sustained by
      intermittent administration of low maintenance doses. Stimulation of the
      adenylate-cyclase/cyclic adenosine monophosphate (cAMP) system appears to be a
      common feature of DCP. Responses to beta-adrenergic stimuli are also diminished.
      Cardiac cAMP triggers the induction of phosphodiesterase (PDE) 1 and 4 isoforms
      and of Na/K-ATPase. Increased amount and activity of PDE isoforms subsequently
      reduces excess myocardial cAMP production. Changes in Na/K-ATPase moderate
      ischemic myocardial potassium loss, sodium, and calcium accumulation, as well as
      the toxicity of ouabain. The future therapeutic challenge is to identify new
      drugs that can mimic DCP.

PMID- 16098599
TI  - An in vitro model of traumatic brain injury utilising two-dimensional stretch of
      organotypic hippocampal slice cultures.
AB  - Traumatic brain injury (TBI) is caused by rapid deformation of the brain,
      resulting in a cascade of pathological events and ultimately neurodegeneration.
      Understanding how the biomechanics of brain deformation leads to tissue damage
      remains a considerable challenge. We have developed an in vitro model of TBI
      utilising organotypic hippocampal slice cultures on deformable silicone
      membranes, and an injury device, which generates tissue deformation through
      stretching the silicone substrate. Our injury device controls the biomechanical
      parameters of the stretch via feedback control, resulting in a reproducible and
      equi-biaxial deformation stimulus. Organotypic cultures remain well adhered to
      the membrane during deformation, so that tissue strain is 93 and 86% of the
      membrane strain in the x- and y-axis, respectively. Cell damage following injury
      is positively correlated with strain. In conclusion, we have developed a unique
      in vitro model to study the effects of mechanical stimuli within a complex
      cellular environment that mimics the in vivo environment. We believe this model
      could be a powerful tool to study the acute phases of TBI and the induced cell
      degeneration could provide a good platform for the development of potential
      therapeutic approaches and may be a useful in vitro alternative to animal models
      of TBI.

PMID- 16098600
TI  - Specificity and efficacy of noradrenaline, serotonin depletion in discrete brain
      areas of Swiss mice by neurotoxins.
AB  - The aim of this work is to define neurotoxins doses to have efficient and
      specific depletion of noradrenaline (NA), serotonin (5-HT) neurotransmission in
      cortex, striatum, hippocampus and hypothalamus of Swiss mice after
      intraperitoneal administration of, respectively, N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine hydrochloride (DSP-4) and para-chlorophenylalanine methyl ester
      hydrochloride (PCPA). The neurotransmitters concentrations were determined by
      high performance liquid chromatography with amperometric detection. The minimal
      single dose necessary to produce a highly significant decrease of NA levels
      (p<0.01 in comparison with control group) in hypothalamus (-44%), hippocampus (
      91%), striatum (-40%) and cortex (-68%) was 50mg/kg but DA and 5-HT levels were
      modified, respectively, in hypothalamus and striatum. Three doses of PCPA 300
      mg/kg over 3 consecutive days involve a profound depletion of 5-HT transmission
      in all discrete brain areas but NA and DA levels were also significantly reduced.
      In conclusion, DSP-4 has a different efficacy in discrete brain areas with a
      noradrenergic specificity which is not absolute, PCPA has a similar efficacy in
      all brain areas but is unspecific of 5-HT transmission.

PMID- 16098601
TI  - A study on symptom profiles of late-life depression: the influence of vascular,
      degenerative and inflammatory risk-indicators.
AB  - BACKGROUND: If specific symptom profiles of depressive disorders in the elderly
      are related to a specific etiology, this could have implications for everyday
      clinical practice. We hypothesized that a "motivational" profile, with symptoms
      such as psychomotor change, loss of interest and loss of energy, could clinically
      separate patients with predominantly vascular or degenerative risk indicators
      from patients with inflammatory risk indicators. METHODS: A total of 4051
      subjects participated in a study on mental health problems in community-dwelling
      elderly. Information on psychiatric symptoms, demographic and medical status,
      previous history and family history was obtained. We distinguished three
      subgroups according to predominant somatic risk-indicators; vascular,
      degenerative and inflammatory groups. RESULTS: Motivational symptoms were
      associated with vascular or degenerative risk-indicators for depression;
      psychomotor change with both indicators; loss of energy with vascular, though
      also with the inflammatory indicator, and thinking/concentration disturbance with
      the degenerative indicator. The so-called mood symptoms of depression, especially
      thoughts of death, were more strongly related with the inflammatory risk
      indicator. Melancholic symptoms like appetite and sleep disturbances were more
      strongly associated with the inflammatory risk-indicator. LIMITATIONS:
      Etiological classification was not confirmed by additional investigations such as
      laboratory findings or MRI brain scans. CONCLUSION: This study showed that in
      patients with a late-life depression specific symptoms of the depressive disorder
      may reflect the predominant underlying pathogenic mechanism.

PMID- 16098602
TI  - Familiality in a five-factor model of schizophrenia psychopathology: findings
      from a 16-month follow-up study.
AB  - We sought to examine stability associations between family history and
      variability of schizophrenia symptoms repeatedly examined during a naturalistic
      follow-up study. The Positive and Negative Syndrome Scale, the Insight and
      Treatment Attitudes Questionnaire, and the Abnormal Involuntary Movement Scale
      were administered to 69 patients with familial and 79 patients with sporadic
      schizophrenia, at hospital admission and at stabilization stage (about 16 months
      later). Analysis of covariance was applied to identify the association of symptom
      factors with familiality of schizophrenia. We found that schizophrenia patients
      with positive family histories had significantly higher dysphoric, activation and
      negative factors. However, familiality of activation and negative factors were
      dependent on additional variables such as age of onset (both factors), baseline
      ratings, insight, and side effects (negative factor). No significant association
      of family history with intensity of positive and autistic preoccupation factors
      was found. Familial schizophrenia is characterized by higher severity of
      dysphoric mood factors that may represent impaired emotional reactivity. It is
      suggested that dysphoric mood may be a useful phenotype for molecular genetic
      studies of schizophrenia with positive family history.

PMID- 16098603
TI  - Genetic selection for high and low immune response in pigs: effects on
      immunoglobulin isotype expression.
AB  - Immunoglobulin (Ig) function varies by isotype and antibody activity is best
      mediated by isotypes most able to control the inciting infection. In pigs, a high
      ratio of IgG1:IgG2 is associated with resistance to disease caused by the extra
      cellular bacterium Actinobacillus pleuropneumoniae. This ratio is controlled by
      type 1/type 2 cytokines in vitro, reflecting cell- (CMI) or antibody-mediated
      immune (AMI) responses, respectively. Animals were used which had been previously
      selectively bred for high (HIR) or low (LIR) combined AMI and CMI and had been
      immunized with hen eggwhite lysozyme (HEWL) in Quil A (days 0 and 14) while
      Bacillus Calmette Guerin was given on day 9. To test the hypothesis that lines do
      not differ in IgG isotype expression as antibody to HEWL, the ratio of anti-HEWL
      associated with IgG1 and IgG2 was determined at days 0, 9, 14 and 21. The ratio
      of IgG1:IgG2-associated antibody was always <1.0 indicating a type 1 response and
      differed significantly over time in HIR and LIR animals. After primary and
      secondary immunizations, the HIR animals' IgG1:IgG2-associated antibody ratio
      increased and approached 1 while for LIR animals the ratio decreased. Thus anti
      HEWL antibody in HIR, but not LIR, approached balance in type 2:type 1
      expression. Individual variation in immune response was frequently significant
      within each immune response group. Thus, proportional production of anti-HEWL
      antibody associated with IgG isotypes varies by individual and differs over time
      as a function of genotype in pigs selectively bred for HIR or LIR.

PMID- 16098604
TI  - FIV-infected cats respond to short-term rHuG-CSF treatment which results in anti
      G-CSF neutralizing antibody production that inactivates drug activity.
AB  - The hematological and virological effects of recombinant human granulocyte colony
      stimulating factor (rHuG-CSF) were evaluated in feline immunodeficiency virus
      (FIV)-infected cats. Six age-matched, FIV-infected cats used in this cross-over
      study were injected subcutaneously with 5 microg/kg of rHuG-CSF daily for 3
      weeks, while six control cats received a placebo. Five of six rHuG-CSF-treated
      cats had significant increases in neutrophil counts that peaked on days 11-21 of
      treatment. All rHuG-CSF-treated cats exhibited an increase in myeloid:erythroid
      ratios of the bone marrow cells without significant changes in lymphocyte, CD4
      counts, CD4/CD8 ratios, RBC counts, FIV antibody titers, and FIV loads in
      peripheral blood, and without clinical and hematological toxicities. Five of six
      rHuG-CSF-treated cats developed antibodies to rHuG-CSF by 14-21 days of
      treatment, which correlated with decreasing neutrophil counts and increasing
      neutralizing antibodies to rHuG-CSF. Three cats re-treated with rHuG-CSF rapidly
      developed neutralizing antibodies to rHuG-CSF, while one cat also developed
      neutralizing antibodies to recombinant feline G-CSF (rFeG-CSF). Overall, rHuG-CSF
      treatment increased neutrophil counts in FIV-infected cats without affecting the
      infection status of cats. However, long-term use of rHuG-CSF is not recommended
      in cats because of the neutralizing antibody production to rHuG-CSF that affects
      the drug activity. In addition, a preliminary finding suggests that repeated
      treatment cycle can also induce cross-neutralizing antibodies to rFeG-CSF, which
      may potentially affect the homeostasis of endogenous FeG-CSF.

PMID- 16098605
TI  - IgA Fc receptors in cattle and horses.
AB  - The biological role of IgA depends, at least partly, on the interaction with
      specific receptors (FcalphaRs) on the surface of leukocytes. The human FcalphaR,
      CD89, was the first IgA Fc receptor to be identified, and binding of IgA-coated
      particles to CD89 triggers numerous cellular effector functions including
      phagocytosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and release
      of inflammatory mediators. Recently, CD89 orthologs have been identified in a
      number of other species, including cows and horses. This brief review will
      summarize our current knowledge regarding the structure and function of bovine
      and equine CD89.

PMID- 16098606
TI  - Bovine toll-like receptor 9: a comparative analysis of molecular structure,
      function and expression.
AB  - Non-methylated CpG motifs, present in viral and bacterial DNA, are one of many
      pathogen-associated molecular patterns (PAMP) recognized by the mammalian innate
      immune system. Recognition of this PAMP occurs through a specific interaction
      with toll-like receptor 9 (TLR9) and this interaction can induce cytokine
      responses that influence both innate and adaptive immune responses. Previous
      investigations determined that both the flanking sequences in synthetic CpG
      oligodeoxynucleotides (CpG ODN) and the cellular pattern of TLR9 expression can
      influence species-specific responses to CpG ODN. Therefore, the structure,
      function and cellular distribution of bovine TLR9 were compared with what is
      known for mice and human. Analysis of the bovine TLR9 gene revealed greater
      sequence homology between cattle and humans than cattle and mice Similar CpG
      motifs induced optimal activation of both human and bovine leukocytes and these
      motifs were distinct from those which activated mouse leukocytes. Functional
      analyses with CpG ODN stimulated bovine blood leukocytes revealed that class A
      CpG ODN were more potent inducers of interferon-alpha (IFN-alpha) than class B
      CpG ODN. Furthermore, magnetic activated cell sorting of bovine blood leukocyte
      subpopulations implicated dendritic cells but not monocytes in the regulation of
      CpG ODN-induced IFN secretion. Thus, the cellular pattern of CpG ODN-induced
      responses in cattle shared many similarities with human leukocytes. Collectively,
      these analyses revealed substantial conservation of TLR9 structure and TLR9
      function in blood leukocytes of humans, cattle and other domestic species.

PMID- 16098607
TI  - Temporal regulation of cytokine mRNA expression in equine recurrent airway
      obstruction.
AB  - Acute and chronic inflammation of the airway remains an important health problem
      for equids. "Heaves" or recurrent airway obstruction (RAO) remains one of the
      most commonly diagnosed conditions affecting the lung of older horses in Europe
      and the United States. The typical clinical signs of RAO include non-productive
      coughing, serous nasal discharge, labored expiratory effort, and flaring of the
      nostrils. Auscultation of the lungs of the affected horse often reveals abnormal
      respiratory sounds, described as crackles and wheezes, throughout the area of the
      lung field. These clinical signs occur secondary to an inflammatory response that
      results in bronchospasm, excessive mucus production and airway obstruction. This
      inflammatory response is characterized by the presence of excessive mucus and
      inflammatory cells, primarily neutrophils, in the small airways. Most evidence
      suggests that RAO is the result of a pulmonary hypersensitivity to inhaled
      antigens. Exposure of affected horses to hay dust, pollens, and mold spores leads
      to neutrophil accumulation in the lung and bronchospasm. The identification of
      allergen-specific IgE in bronchoalveolar lavage (BAL) fluid and sera of affected
      horses supports the involvement of a late phase, IgE-mediated, hypersensitivity
      reaction in the pathogenesis of equine RAO. The production of IgE antibodies is
      regulated by the cytokines IL-4 and IL-13. Using a quantitative PCR method we
      have reported that horses with RAO exhibit a modified Type 2 cytokine response
      characterized by the production of IL-4 and IL-13 mRNA, but not IL-5 mRNA in BAL
      cells. Interferon-gamma mRNA was also elevated, suggesting a mixed response.
      While these results are consistent with equine RAO being the result of an
      aberrant Type 2 cytokine response to inhaled allergens, others have failed to
      find any evidence of elevated Type 2 cytokine mRNA in BAL from horses with
      "heaves". It is likely that these disparate results could be the result of
      differences in the clinical stage of the affected animals or the timing of sample
      collection. Here, we report a diverse pattern of cytokine gene expression when
      sampling a group of affected horses over a period of time.

PMID- 16098608
TI  - Comparative genetics and innate immune functions of collagenous lectins in
      animals.
AB  - Collagenous lectins such as mannan-binding lectins (MBLs), ficolins (FCNs),
      surfactant proteins A and D (SP-A, SP-D), conglutinin (CG), and related ruminant
      lectins are multimeric proteins with carbohydrate-binding domains aligned in a
      manner that facilitates binding to microbial surface polysaccharides. MBLs and
      FCNs are structurally related to C1q, but activate the lectin complement pathway
      via interaction with MBL-associated serine proteases (MASPs). MBLs, FCNs, and
      other collagenous lectins also bind to some host macromolecules and contribute to
      their removal. While there is evidence that some lectins and the lectin
      complement pathway are conserved in vertebrates, many differences in collagenous
      lectins have been observed among humans, rodents, and other vertebrates. For
      example, humans have only one MBL but three FCNs, whereas most other species
      express two FCNs and two MBLs. Bovidae express CG and other SP-D-related
      collectins that are not found in monogastric species. Some dysfunctions of human
      MBL are due to single nucleotide polymorphisms (SNPs) that affect its expression
      or structure and thereby increase susceptibility to some infections. Collagenous
      lectins have well-established roles in innate immunity to various microorganisms,
      so it is possible that some lectin genotypes or induced phenotypes influence
      resistance to some infectious or inflammatory diseases in animals.

PMID- 16098609
TI  - DNA vaccination against Japanese cedar pollinosis in dogs suppresses type I
      hypersensitivity by controlling lesional mast cells.
AB  - Sensitization to allergens of Japanese cedar pollen is known to cause canine
      atopic dermatitis as approximately 10% of atopic dogs in Japan were positive to
      the pollen allergen. Among the two major allergens of Japanese cedar pollen,
      since Cry j 1 is more important than Cry j 2 as an antigen to increase IgE in
      atopic dogs sensitized to Japanese cedar pollen, Cry j 1 can be a target for
      immunotherapy. In our study, efficacy of DNA vaccination with a plasmid
      containing the gene of a major allergen of Japanese cedar (Cryptomeria japnonica,
      CJ) pollen, Cry j 1, was examined using a dog model experimentally sensitized to
      CJ pollen allergen. Cry j 1 DNA plasmid and a vector plasmid (pCAGGS) were
      injected into six dogs and three dogs, respectively, five times with an interval
      of 1.5 month. After the treatment with Cry j 1 DNA plasmid, production of IgE
      against Cry j 1 decreased in four of the six dogs in the treatment group, whereas
      it increased in the three dogs of the control group. The reactivity to the pollen
      allergen in intradermal testing and provocation testing were obviously reduced in
      the treatment group, but not in the control group. The number of mast cells in
      alveolar area of the lung in the treatment group was smaller than that in the
      control group. Cry j 1 DNA plasmid was also injected into three atopic dogs
      sensitive to Cry j 1, resulting in improvement of clinical signs in the
      pollination season. These findings indicated that Cry j 1 DNA plasmid could
      regulate mast cell-mediated reaction against Cry j 1, which could be an
      alternative and effective treatment for CJ pollinosis.

PMID- 16098610
TI  - The host-parasite relationship in bovine neosporosis.
AB  - Infection with the protozoan parasite Neospora caninum is thought to be a major
      cause of reproductive failure in cattle worldwide. Cattle infected with the
      parasite are three to seven times more likely to abort compared to uninfected
      cattle. The parasite may be transmitted to cattle through the ingestion of
      oocysts that are shed in the faeces of acutely infected dogs (definitive host of
      N. caninum) or by congenital infection from mother to foetus via the placenta.
      Interestingly, transplacental transmission can occur over consecutive pregnancies
      and congenitally infected heifers can transmit the parasite to their own
      offspring. This repeated vertical transmission observed in naturally infected
      cattle suggests that cattle do not easily develop effective immunity to the
      parasite, presenting a significant challenge to the development of a control
      strategy based on vaccination. Neosporosis is a disease of pregnancy and studying
      the bovine maternal and foetal immune responses during pregnancy will help us to
      understand the change in the balance between the parasite and the host that may
      result in disease of the foetus. Studies in non-pregnant cattle and in murine
      models of infection have shown the importance of T-helper 1-type immune responses
      involving pro-inflammatory cytokines, such as IFNgamma and IL-12, in limiting
      intracellular multiplication of the parasite. During pregnancy, changes occur in
      the immune system allowing the mother to accept the foetal allograft. Research in
      other species has stressed the crucial role of T-helper 2-type cytokines at the
      materno-foetal interface in maintaining the pregnancy and regulating the
      potentially damaging effect of Th-1 responses. Studies in cattle have shown that
      cell proliferation and IFNgamma responses may be significantly down-regulated
      around mid-gestation. This may mean that cattle are less able to cope with N.
      caninum infection at this time and are more likely to transmit the parasite to
      the foetus. Another important factor is the gestational age and hence immuno
      competence of the foetus at the time of infection. Early in gestation, N. caninum
      infection of the placenta and subsequently the foetus usually proves fatal,
      whereas infection occurring in mid to late pregnancy may result in the birth of a
      congenitally infected but otherwise healthy calf. Studies of foetal immune
      responses have shown that at 14 weeks of gestation, lymphocytes only respond to
      mitogen, while by 24 weeks (mid-gestation), they respond to antigen by
      proliferating and releasing IFNgamma. Clearly, there are several factors
      influencing the outcome of N. caninum infection in pregnancy: the timing,
      quantity and duration of parasitaemia, the effectiveness of the maternal immune
      response and the ability of the foetus to mount an immune response against the
      parasite. The challenge is to design a vaccine that will prevent foetal infection
      by N. caninum. This is likely to involve a fine balancing act with the immune
      system that will allow intervention in a manner that will tip the host-parasite
      balance in favour of the host without compromising the pregnancy.

PMID- 16098611
TI  - The use of a systemic prime/mucosal boost strategy with an equine influenza ISCOM
      vaccine to induce protective immunity in horses.
AB  - In horses, natural infection confers long lasting protective immunity
      characterised by mucosal IgA and humoral IgGa and IgGb responses. In order to
      investigate the potential of locally administered vaccine to induce a protective
      IgA response, responses generated by vaccination with an immunostimulating
      complex (ISCOM)-based vaccine for equine influenza (EQUIP F) containing
      A/eq/Newmarket/77 (H7N7), A/eq/Borlange/91 (H3N8) and A/eq/Kentucky/98 (H3N8)
      using a systemic prime/mucosal boost strategy were studied. Seven ponies in the
      vaccine group received EQUIP F vaccine intranasally 6 weeks after an initial
      intramuscular immunisation. Following intranasal boosting a transient increase in
      virus-specific IgA was detected in nasal wash secretions. Aerosol challenge with
      the A/eq/Newmarket/1/93 reference strain 4 weeks after the intranasal booster
      resulted in clinical signs of infection and viral shedding in seven of seven
      influenza-naive control animals whereas the seven vaccinated ponies had
      statistically significantly reduced clinical signs and duration of virus
      excretion. Furthermore, following this challenge, significantly enhanced levels
      of virus-specific IgA were detected in the nasal washes from vaccinated ponies
      compared with the unvaccinated control animals. These data indicate that the
      intranasal administration of EQUIP F vaccine primes the mucosal system for an
      enhanced IgA response following exposure to live influenza virus.

PMID- 16098614
TI  - Protective effects of a peroxisome proliferator-activated receptor-beta/delta
      agonist in experimental autoimmune encephalomyelitis.
AB  - Agonists of the peroxisome proliferator-activated receptor gamma (PPARgamma)
      exert anti-inflammatory and anti-proliferative effects which led to testing of
      these drugs in experimental autoimmune encephalomyelitis (EAE), a model for
      multiple sclerosis. In contrast, the effect of PPARdelta (PPARdelta) agonists in
      EAE is not yet known. We show that oral administration of the selective PPARdelta
      agonist GW0742 reduced clinical symptoms in C57BL/6 mice that had been immunized
      with encephalitogenic myelin oligodendrocyte glycoprotein (MOG) peptide. In
      contrast to previous results with PPARgamma agonists, GW0742 only modestly
      attenuated clinical symptoms when the drug was provided simultaneously with
      immunization, but a greater reduction was observed if administered during disease
      progression. Reduced clinical symptoms were accompanied by a reduction in the
      appearance of new cortical lesions, however cerebellar lesion load was not
      reduced. Treatment of T-cells with GW0742 either in vivo or in vitro did not
      reduce IFNgamma production; however GW0742 reduced astroglial and microglial
      inflammatory activation and IL-1beta levels in EAE brain. RTPCR analysis showed
      that GW0742 increased expression of some myelin genes. These data demonstrate
      that PPARdelta agonists, like other PPAR ligands, can exert protective actions in
      an autoimmune model of demyelinating disease.

PMID- 16098615
TI  - The value of Ems Mineral Salts in the treatment of rhinosinusitis in children.
      Prospective study on the efficacy of mineral salts versus xylometazoline in the
      topical nasal treatment of children.
AB  - The treatment of rhinosinusitis seen in the light of uncertain pathogenesis and
      variable symptoms is under discussion and ranges from the administration of
      antibiotics, decongestants and anti-allergic agents to no treatment. In this
      randomized, prospective, double-blind and controlled study the effect of a 14-day
      treatment (1-2 sprays into each nostril t.d.) with either isotonic Ems Mineral
      Salts (EMS) solution (Siemens & Co., Bad Ems, Germany) or xylometazoline solution
      (0.05%) was tested in children (n=66) aged 2-6 years. MAIN OUTCOMES: the degree
      of mucosal inflammation, nasal patency, general state of health, condition of the
      middle ear, auditory function as well as an assessment of complaints by the
      parents. With the exception of the hearing defects, all parameters showed a clear
      improvement in both treatment groups at the end of the observation period
      (p>0.001). The hearing defects showed only a trend towards improvement. At the
      end of the study no differences between the treatment groups could be determined.
      However, at the intermediate examination after the first 7 days of treatment more
      favourable results were seen in the group treated with EMS. No undesired
      medicinal effects were observed, although in 7 out of 34 cases the nasal spray
      was improperly used in the group treated with xylometazoline. The results of the
      study show that there is no difference in efficacy between an exclusive treatment
      by EMS solution in children aged 2-6 years and a treatment with xylometazoline,
      but with the distinction that with EMS the length of use was not restricted,
      there were not the potential side effects of nasal decongestants, and there was
      no contraindication in the newborn and infants.

PMID- 16098618
TI  - Surface plasmon resonance for real-time evaluation of immobilized
      fructosyltransferase activity.
AB  - The extracellular enzyme fructosyltransferase (FTF) is considered to be a
      significant virulence factor in the dental biofilm. We have developed a method
      using surface plasmon resonance to detect the activity of immobilized FTF in
      situ. This real time technique provides a sensitive direct assay for
      characterizing functional properties of immobilized enzymes such as FTF.

PMID- 16098619
TI  - Prognostic value of tumor oxygenation in 397 head and neck tumors after primary
      radiation therapy. An international multi-center study.
AB  - PURPOSE: To analyze the relationship between pre-treatment measurements of tumor
      oxygen tension (pO2) and survival in advanced head and neck cancer. PATIENTS AND
      METHODS: Eppendorf pO2 measurements in 397 patients from seven centers were
      analyzed using the fraction of pO2 values < or =2.5 mmHg (HP2.5), < or =5 mmHg
      (HP5) and median tumor pO2 (mmHg) as descriptors. All patients had intended
      curative radiation therapy alone or as pre- or post-operative radiotherapy or
      radio-chemotherapy according to the practice at each center. RESULTS: The degree
      of hypoxia varied between tumors with an overall median tumor pO2=9 mmHg (range 0
      62 mmHg), a median HP2.5=19% (range 0-97%) and HP5=38%, (range 0-100%). By
      quadratic regression median tumor pO2 correlated with Hb (2P=0.026, n=357), while
      HP2.5 or HP5 did not. HP2.5 above the population median was the only parameter
      that associated with poor overall survival (Kaplan Meier analysis, P=0.006). In a
      multivariate Cox Proportional Hazards analysis, stratified according to
      institution HP2.5 was by far the most statistically significant factor in
      explaining the variability in survival. After adjusting for HP2.5, clinical
      stage, radiation dose and surgery hemoglobin concentration was not significant in
      the model. The prognostic model shows that the 5-year survival is almost constant
      for HP2.5 values in the range from 0 to 20%, whereas the 5-year survival
      approaches 0% in the most hypoxic tumors. CONCLUSION: This study provides
      evidence that tumor hypoxia is associated with a poor prognosis in patients with
      advanced head and neck cancer.

PMID- 16098620
TI  - Influence of oxygen concentration and pH on expression of hypoxia induced genes.
AB  - BACKGROUND AND PURPOSE: This study was designed to determine the oxygen
      dependency for expression of the endogenous hypoxic markers carbonic anhydrase IX
      (protein: CAIX/gene: CA9), glucose transporter 1 (GLUT1/GLUT1), osteopontin
      (OPN/OPN) and lactate dehydrogenase A (LDH-A/LDHA), and how this expression was
      influenced by extracellular pH (pHe). MATERIALS AND METHODS: Human cervix
      squamous cell carcinoma (SiHa) cells were used in all experiments. These cells
      were gassed in an enclosed environment under either anoxia (95% N2+5% CO2) for
      various times (0-30 h) or under different oxygen concentrations (0-21% O2) for 24
      h at normal pHe (7.4) or low pHe (6.3). Response to radiation (7 Gy) was
      estimated using a clonogenic assay. Gene expression was determined by real-time
      PCR (normalized to the housekeeping gene, TFRC) and protein expression by Western
      blots. RESULTS: Under normal pHe conditions, CA9, GLUT1 and LDHA gene expression
      was upregulated within 1-3h of anoxia, reaching near maximal values by 6h. OPN
      showed a slow increase over 24 h. At 24 h the relative increase was 135, 12, 90
      and 5 times for CA9, GLUT1, OPN and LDHA, respectively. No induction was seen
      with the EGF receptor (EGFR). Gassing cells with differing oxygen concentrations
      for 24h resulted in a maximum level of expression for CA9 at 1% oxygen, whereas
      with GLUT1 and LDHA maximal expression occurred at 0.01% oxygen, but at 0% oxygen
      with OPN. The oxygen dependency for radiation response was identical to that seen
      for GLUT1 and LDHA. Expression of CA9, GLUT1, OPN and LDHA was inhibited under
      hypoxic conditions when pHe was reduced to 6.3. Expression of CAIX protein
      mimicked the CA9 gene expression patterns. CONCLUSION: The expression of all the
      endogenous markers were upregulated by hypoxia, but the timing and oxygen
      dependencies were different and their expression was influenced by low pHe. This
      raises concerns about the generalised use of these agents as markers for hypoxia.

PMID- 16098621
TI  - The hypoxic proteome is influenced by gene-specific changes in mRNA translation.
AB  - BACKGROUND AND PURPOSE: Hypoxia causes a rapid reduction in mRNA translation
      efficiency. This inhibition does not affect all mRNA species to the same extent
      and can therefore contribute significantly to hypoxia-induced differential
      protein expression. Our aim in this study was to characterize changes in gene
      expression during acute hypoxia and evaluate the contribution of regulation via
      mRNA translation on these changes. For each gene, the contribution of changes in
      mRNA abundance versus mRNA translation was determined. MATERIALS AND METHODS:
      DU145 prostate carcinoma cells were exposed to 4h of hypoxia (<0.02% O2).
      Efficiently translated mRNAs were isolated by sedimentation through a sucrose
      gradient. Affymetrix microarray technology was used to evaluate both the
      transcriptional and translational contribution to gene expression. Results were
      validated by quantitative PCR. RESULTS: One hundred and twenty genes were more
      than 4-fold upregulated by hypoxia in the efficiently translated fraction of
      mRNA, in comparison to only 76 genes at the level of transcription. Of the 50
      genes demonstrating the largest changes in translation, 11 were found to be more
      than 2-fold over represented in the translated fraction in comparison to their
      overall transcriptional level. The gene with the highest translational
      contribution to its induction was CITED-2, which is a negative regulator of HIF-1
      transcriptional activity. CONCLUSIONS: Gene-specific regulation of mRNA
      translation contributes significantly to differential gene expression during
      hypoxia.

PMID- 16098622
TI  - Perception-action coupling and expertise in interceptive actions.
AB  - The goal of this experiment was to show that expertise in interceptive actions
      can be explained by a shorter delay in movement regulation. In this contribution,
      we tested tennis experts and non-experts using a simulated interceptive task. The
      experimental device simulated linear motion of an object toward a target on a
      horizontal runway. Participants had to intercept the simulated moving object with
      their right hand holding a cart that could slide along a horizontal track
      perpendicular to the runway. Three different velocity conditions were used: a
      constant velocity condition that maintained the initial velocity (2m/s) constant
      until arriving on the target; the decelerated and accelerated velocity
      conditions, in which the velocity suddenly changed (400 ms before its arrival on
      the target) from 2 to 1m/s or 3m/s, respectively. Timing accuracy and movement
      correction after the unexpected velocity change were analysed. The experts were
      more accurate in the decelerative case (-29 and -124 ms respectively), in the
      accelerative case (69 and 116 ms respectively), but not in the constant velocity
      case (2 and 13 ms respectively). Findings can be explained by the shorter visuo
      motor delay (VMD: the time required to adapt the movement to the new velocity)
      for the experts (162 ms) than for the non-experts (221 ms). This shorter VMD
      offers more time to adapt the interceptive movement to the new velocity. These
      results can be interpreted as an optimization of the perception-action coupling
      with expertise.

PMID- 16098623
TI  - Combined sulfite method for the measurement of the oxygen transfer coefficient
      k(L)a in bio-reactors.
AB  - The combined sulfite method is proposed for the measurement of oxygen transfer
      coefficients, k(L)a, in bio-reactors. The method consists of a steady-state and a
      dynamic measurement which are carried out under the same experimental conditions
      and thus yield data for both methods during one experiment. The applied
      experimental conditions are shown to avoid chemical enhancement during the steady
      state measurement. Moreover, no parallel sulfite oxidation occurs during the
      oxygen saturation phase of the dynamic measurement. Under the applied
      experimental conditions, no information about the sulfite oxidation kinetics is
      required and possible metal ion impurities in sulfite salts do not influence the
      measurement. The characterization of a laboratory-scale bioreactor aerated with
      pure oxygen yields k(L)a values during the steady-state and the dynamic
      measurements that are in good agreement with the dynamic pressure method, the
      correctness of which is generally accepted. When air is used for absorption, the
      steady-state measurement yields k(L)a values that correlate to the correct
      variant of the standard dynamic method. The dynamic measurement with air
      absorption yields a k(L)a value which considers the influence of the non-uniform
      bubble size distribution present in bubble-aerated bio-reactors.

PMID- 16098624
TI  - Plasticizing effect of water on poly(lactide-co-glycolide).
AB  - The purpose of this research was to evaluate the effect and nature of hydration
      on the glass transition temperature (Tg) of poly(D,L-lactide-co-glycolide) and
      investigate the physical state of water within the polymer during hygrothermal
      aging. The polymer was incubated in water at 23, 30, 37 and 55 degrees C, while
      the vapor sorption studies were carried out at 37 degrees C using saturated salt
      solutions. The water content and the thermal behavior of PLGA-water system were
      assessed by Karl Fischer titration and modulated differential scanning
      calorimetry, respectively, the hygrothermal aging was monitored by gel permeation
      chromatography. Water depressed reversibly the Tg by about 15 degrees C
      regardless of the incubation conditions. The Tg then remained constant at
      approximately 30 degrees C for five days, except when degradation occurred. A
      broad ice melting peak was detected around 0 degrees C. In the sorption studies,
      a linear correlation (r2 0.9837) between the Tg and the moisture content was
      observed in the range of 0.3-2.6% w/w, but there was no discernible endothermic
      event associated with the melting of ice. Data were found to fit reasonably well
      to the Gordon-Taylor/Kelley-Bueche equation. There were no differences between
      bulk and vapor water aging. It is proposed that the water responsible for
      plasticizing the polymer was non-freezable (bound) water and the small fraction
      of such water which was absorbed at high relative humidity caused polymer
      degradation in the same manner as bulk water.

PMID- 16098625
TI  - Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: The molecular mechanisms of hepatocarcinogenesis remain largely
      unknown. Previous studies suggest that activation of the Wnt/beta-catenin pathway
      is important during hepatocyte transformation but the role of Frizzled receptor
      (FZD) in this process has not been defined. Here we investigate activation of
      this pathway by FZD using transgenic hepatocellular carcinoma (HCC) murine
      models. METHODS: We employed single (c-myc, SV40-Tag) and established double
      [insulin receptor substrate-1 (IRS-1/c-myc) and hepatitis Bx protein (X/c-myc)]
      transgenic lines and all developed HCC. Expression of 9 FZD was measured by real
      time RT-PCR and Western blot analysis. Phosphorylation and cellular accumulation
      of beta-catenin were assessed in both dysplastic tissue and tumors. We
      investigated the effect of a dominant negative (DN) FZD7 on TCF transcriptional
      activity in a SV40 derived HCC cell line. RESULTS: FZD7 was highly overexpressed
      at the mRNA and protein level(s) in HCC and occurred in dysplasia. Upregulation
      of FZD7 was associated with reduced phosphorylation of beta-catenin and led to
      nuclear accumulation in HCC tumors. Ectopic expression of a DN FZD7 construct
      decreased TCF transcriptional activity in tumor cells. CONCLUSIONS: These
      observations suggest that upregulation of FZD7 receptors in association with
      activation of the canonical Wnt/beta-catenin pathway is a common molecular event
      in HCC.

PMID- 16098626
TI  - Prognostic evaluation of alcoholic hepatitis.

PMID- 16098627
TI  - Mutagenic effects of ribavirin and response to interferon/ribavirin combination
      therapy in chronic hepatitis C.
AB  - BACKGROUND/AIMS: To elucidate whether ribavirin acts as a mutagen in the clinical
      setting and to clarify the relationship between ribavirin-induced mutations and
      virological response to combined therapy. METHODS: Thirty-four patients with
      hepatitis C virus (HCV) genotype 1b received ribavirin monotherapy for 4 weeks,
      followed by a 24-week course of IFN/ribavirin therapy. HCV mutations during a non
      treatment observation period and during subsequent ribavirin monotherapy were
      determined, and the relationship between mutations and response to subsequent
      IFN/ribavirin therapy was evaluated. RESULTS: Serum HCV significantly decreased
      from 6.90 to 6.56 log10copy/ml in response to ribavirin monotherapy (P < 0.0001).
      Nucleotide mutations in the NS5A and NS5B regions occurred during ribavirin
      monotherapy at a rate of 2.9 x 10(-2)/site/year and 1.3 x 10(-2)/site/year,
      respectively, a significantly higher rate than the mutation rates during the
      prior non-treatment observation period (0.60 x 10(-2)/site/year and 0.24 x 10(
      2)/site/year, P = 0.02, respectively). Mutation rates in the NS5A region were
      significantly higher in sustained viral responders (SVRs, n = 10) than in non
      responders (8.8 x 10(-2)/site/year vs. 0.38 x 10(-2)/site/year, P = 0.0005,
      respectively). In the NS5A region, non-synonymous mutations only occurred in
      SVRs. CONCLUSIONS: Ribavirin may act as a mutagen, and mutations occurring during
      ribavirin therapy correlate with the virological response to subsequent
      IFN/ribavirin combination therapy.

PMID- 16098628
TI  - Deficient Stat3 DNA-binding is associated with high Pias3 expression and a
      positive anti-apoptotic balance in human end-stage alcoholic and hepatitis C
      cirrhosis.
AB  - BACKGROUND/AIMS: In vitro and animal data suggest that alcohol and hepatitis C
      virus (HCV) proteins might interfere with Stat3 signaling, a potential regulator
      of liver cell apoptosis and proliferation. METHODS: We assessed Stat3 expression,
      activity and the apoptotic-proliferation balance in end-stage HCV and alcoholic
      liver disease (ALD) in man. Explanted livers of HCV and ALD patients were
      compared to normal and primary biliary cirrhosis (PBC) livers. RESULTS: Although
      Stat3 expression and phosphorylation was not altered in HCV and ALD cirrhosis,
      Stat3 DNA-binding was not detected in all ALD and most HCV samples. Deficient
      Stat3 DNA-binding was associated with high Pias3 expression, but not with
      increased Socs3 levels. Bcl-2 was up-regulated in HCV and ALD together with
      decreased Caspase3 activity. Compared to base-line cell proliferation in normal
      donor livers, HCV cirrhosis showed a marked reduction in cyclin D1 and PCNA,
      whereas both markers were only slightly reduced in ALD. CONCLUSIONS: End-stage
      HCV and ALD cirrhosis is characterized by impaired Stat3 DNA-binding possibly
      through up-regulation of Pias3. Therefore, impaired activation of Stat3 target
      genes might contribute to disturbed liver regeneration and repair. The attempt in
      cirrhotic livers to favor anti-apoptotic over pro-apoptotic pathways is not
      sufficient to compensate for the low cellular proliferation rates.

PMID- 16098629
TI  - Multievidence microarray mining.
AB  - Microarray mining is a challenging task because of the superposition of several
      processes in the data. We believe that the combination of microarray data-based
      analyses (statistical significance analysis of gene expression) with array
      independent analyses (literature-mining and promoter analysis) enables some of
      the problems of traditional array analysis to be overcome. As a proof-of
      principle, we revisited publicly available microarray data derived from an
      experiment with platelet-derived growth factor (PDGF)-stimulated fibroblasts. Our
      strategy revealed results beyond the detection of the major metabolic pathway
      known to be linked to the PDGF response: we were able to identify the
      crosstalking regulatory networks underlying the metabolic pathway without using a
      priori knowledge about the experiment.

PMID- 16098630
TI  - The evolution of noncoding DNA: how much junk, how much func?
AB  - Comparative sequence analysis on a genomic scale has opened the door for the
      systematic analysis of cis-acting regulatory DNA. It is now possible to begin to
      answer basic questions such as, how much meaningful noncoding sequence is in the
      genome? How strong is natural selection on functional noncoding sequences in
      different species? Two recent articles have capitalized on the comparative
      genomic approach in an attempt to answer these questions with surprising results.

PMID- 16098631
TI  - Cnidarians and ancestral genetic complexity in the animal kingdom.
AB  - Eleven of the twelve recognized wingless (Wnt) subfamilies are represented in the
      sea anemone Nematostella vectensis, indicating that this developmentally
      important gene family was already fully diversified in the common ancestor of
      'higher' animals. In deuterostomes, although duplications have occurred, no novel
      subfamilies of Wnts have evolved. By contrast, the protostomes Drosophila and
      Caenorhabditis have lost half of the ancestral Wnts. This pattern -- loss of
      genes from an ancestrally complex state -- might be more important in animal
      evolution than previously recognized.

PMID- 16098632
TI  - Do disparate mechanisms of duplication add similar genes to the genome?
AB  - Gene duplication is the fundamental source of new genes. Biases in duplication
      have profound implications for the dynamics of gene content during evolution. In
      this article, we compare genes arising from whole gene duplication (WGD), smaller
      scale duplication (SSD) and singletons in Saccharomyces cerevisiae. Our results
      demonstrate that genes duplicated by WGD and SSD are similarly biased with
      respect to codon bias and evolutionary rate, although differing significantly in
      their functional constituency.

PMID- 16098633
TI  - Novel patterns of gene expression in polyploid plants.
AB  - Genome doubling, or polyploidy, is a major factor accounting for duplicate genes
      found in most eukaryotic genomes. Polyploidy has considerable effects on
      duplicate gene expression, including silencing and up- or downregulation of one
      of the duplicated genes. These changes can arise with the onset of
      polyploidization or within several generations after polyploid formation and they
      can have epigenetic causal factors. Many expression alterations are organ
      specific. Specific genes can be independently and repeatedly silenced during
      polyploidization, whereas patterns for other genes appear to be more stochastic.
      Three recent reports have provided intriguing new insights into the patterns,
      timing and mechanisms of gene expression changes that accompany polyploidy in
      plants.

PMID- 16098634
TI  - Establishment of a non-human primate Campylobacter disease model for the pre
      clinical evaluation of Campylobacter vaccine formulations.
AB  - Campylobacter jejuni is a common cause of enteritis worldwide. The mechanisms by
      which C. jejuni causes disease are unclear. Challenge studies in humans are
      currently considered unethical due to the possibility of severe complications,
      such as Guillain-Barre syndrome. Campylobacter infection in non-human primates
      closely mimics the disease and immune response, seen in humans. In this study, we
      attempted to determine the minimal dose of a pathogenic C. jejuni 81-176 strain
      required for clinical signs and symptoms of disease (> or = 80% attack rate) in
      Macaca mulatta monkeys using an escalating dosage (three doses for three monkey
      groups: 10(7), 10(9) and 10(11) cfu). Eighty percent of the monkeys challenged
      with highest dose (10(11) cfu) had mild disease, but the 80% attack rate
      (moderate diarrhea in 80% of the monkeys) was not achieved. However, 100% of
      monkeys showed IgA seroconversions (three-fold over pre-challenge titers). The
      elicited immune response was challenge dose-dependent. Campylobacter antigen
      specific fecal s-IgA responses were observed in all challenged groups but the
      response was not dose-dependent. Only IgM antibody secreting cells response was
      observed against Campylobacter antigens. The elicited immune response in three
      groups of rhesus monkeys was dose-dependent, indicating this monkey model can be
      used for pre-clinical evaluation of Campylobacter candidate vaccines, however
      these adult rhesus monkeys are less prone to Campylobacter infection.

PMID- 16098635
TI  - Efficacy of a locally produced, Chinese Vi polysaccharide typhoid fever vaccine
      during six years of follow-up.
AB  - A locally produced Vi polysaccharide vaccine against typhoid fever was licensed
      in China following two placebo-controlled, efficacy trials conducted in the early
      1990s in Baoying, Jiangsu Province, and Quan-zhou, Guangxi Province. The two
      trials each enrolled over 80,000 participants and followed participants for 12
      and 19 months post-vaccination, respectively. To define the long-term efficacy of
      this vaccine, we retrospectively assessed the occurrence of typhoid fever,
      diagnosed with clinical and serological criteria, in the two study populations
      for 6 years following vaccination. During the second year following vaccination,
      vaccine efficacy was 100% (95% CI: 17%, 100%) in Baoying and 85% (95% CI: 49%,
      96%) in Quan-zhou. There was suggestive protection (51%; PE: -95%, 88%) during
      the third year in Baoying, nearly identical to the level observed in the third
      year of an earlier trial in South Africa. These results confirm that this vaccine
      protects for at least 2 years, and are consistent with the assertion that the
      vaccine protects for at least 3 years.

PMID- 16098636
TI  - A short report on highlights of world-wide development of RIX4414: a Latin
      American experience.
AB  - An oral, human-derived monovalent (G1P1A) rotavirus vaccine, strain RIX4414, has
      been developed by GlaxoSmithKline, Rixensart, Belgium. The safety, immunogenicity
      and efficacy of this vaccine were evaluated in a randomized, double-blind,
      placebo-controlled, phase IIb trial conducted in Brazil, Mexico and Venezuela.
      Healthy infants were given two doses of vaccine (104.7, 105.2 or 105.8 ffu) or
      placebo at age 2 and 4 months, with routine DTPw-HBV and Hib vaccines. OPV was
      given separately, at least 2 weeks before or after administration of the study
      vaccine. A total of 2155 infants were enrolled, of whom 1618 received one of the
      three vaccine viral concentrations and 537 were given placebo. Analysis of
      efficacy included diarrheal episodes occurring from 2 weeks after second dose
      until one year of age. Efficacy rates against any rotavirus gastroenteritis,
      severe rotavirus gastroenteritis and hospitalizations for rotavirus disease were
      as high as 70% (46-84%; 95%CI), 86% (63-96%; 95%CI), and 93% (54-100%; 95%CI),
      respectively. For non-G1 (mainly G9) serotypes, RIX4414 vaccine conferred
      protection as high as 83% (40-97%; 95%CI) against severe gastroenteritis. A
      decrease was noted in the incidence of severe rotavirus-related gastroenteritis
      after first dose. It is demonstrated that two doses of RIX4414 are highly
      efficacious against severe rotavirus gastroenteritis and hospitalization,
      including disease caused by non-G1 strains, namely G9 serotypes.

PMID- 16098637
TI  - Delivery of heterologous protein antigens via hemolysin or autotransporter
      systems by an attenuated ler mutant of rabbit enteropathogenic Escherichia coli.
AB  - In this report, we describe the use of an attenuated regulatory mutant of a
      rabbit enteropathogenic Escherichia coli (rEPEC) as a live vaccine vector to
      deliver heterologous protein antigens using two dedicated transport systems, a
      Salmonella autotransporter and the E. coli hemolysin apparatus. We previously
      reported that an isogeneic ler (LEE encoded regulator) mutant of rEPEC O103:H2 is
      attenuated and immunogenic in rabbits. We first evaluated the Salmonella
      autotransporter MisL containing the immunodominant B-cell epitope of the
      circumsporozoite protein from Plasmodium falciparum, (NANP)8, fused to the C
      terminal translocator domain under the control of the constitutive Tac17
      promoter. The rEPEC ler mutant was able to express and to translocate the (NANP)8
      passenger peptide to the bacterial surface. We next investigated the delivery of
      Shiga toxin B subunit (Stx1B) from human enterohemorrhagic E. coli by the rEPEC
      ler mutant via the MisL autotransporter or the E. coli hemolysin secretion
      apparatus. The autotransporter and hemolysin plasmids expressed similar levels of
      Stx1B (30-40 ng/ml/OD600). Only 6% of Stx1B was found in the autotransporter
      supernatants; the rest was cell-associated, with a small fraction of the Stx1B
      surface-exposed as determined by immunofluorescence. In contrast, 88% of Stx1B
      was secreted into culture supernatants by the hemolysin secretion system. In an
      in vivo study, no significant protection was observed in rabbits inoculated with
      the ler mutant harboring the Stx1B-autotransporter plasmid following experimental
      challenge with RDEC-H19A, the prototype rEPEC containing an Stx-converting phage.
      In contrast, rabbits inoculated with the rEPEC ler mutant containing the Stx1B
      hemolysin fusion were partially protected from RDEC-H19A infection as
      demonstrated by decreased weight loss (p<0.008) when compared to rabbits
      inoculated with the parent ler mutant. Our results suggest that attenuated rEPEC
      are capable of serving as vaccine vectors to express heterologous protein
      antigens from different cellular locations and deliver these antigens to the
      intestinal mucosa. With this system, secreted proteins may be more effective than
      cell-associated antigens in generating protection.

PMID- 16098638
TI  - Factors influencing the protective efficacy of a BCG homologous prime-boost
      vaccination regime against tuberculosis.
AB  - Tuberculosis due to Mycobacterium spp. continues to represent a major threat to
      human and animal health, prompting the search for effective vaccines. We have
      previously reported a sequential prime and boost homologous vaccination regime,
      using live avirulent M. bovis bacille Calmette-Guerin (BCG) strain 1173P2, that
      can provide significant protection to red deer (Cervus elaphus) against virulent
      M. bovis infection. Here, we have investigated the influence of varying the time
      periods during and following the vaccination regime on the subsequent outcome of
      disease following post-vaccination pathogen challenge. Deer vaccinated using the
      standard regime of BCG-prime (week 0) and BCG-boost (week 8) followed by M. bovis
      challenge (week 14-16) were highly protected, showing significant reductions in
      the incidence of M. bovis infection and tuberculous lesions, as well as reduced
      pathogen burdens in sentinel lymphatic tissues. Decreasing the time-period
      between primary and secondary immunisations from 8 to 4 weeks had no significant
      impact on the protective efficacy afforded by BCG vaccination, while increasing
      this period to 43 weeks largely ablated protection. Increasing the time-period
      between secondary immunisation and M. bovis challenge from 6 to 26 or 52 weeks
      also had no significant impact on protection, suggesting that an appropriately
      timed BCG prime-boost vaccination regime can establish long-lasting protective
      immunological memory in deer. Finally, increasing the time-period between
      virulent M. bovis challenge and the subsequent post-mortem examination of disease
      outcome indicated that - once vaccinated by the standard prime-boost regime -
      deer remain refractory to disease if challenged and maintained for up to 52
      weeks, suggesting that vaccinated animals harbouring low numbers of virulent M.
      bovis organisms do not succumb to disease activation over time. These findings
      are discussed in relation to concurrent measurements of in vivo and ex vivo
      immunological markers of disease and protection, as well as the wider
      implications of a standardised vaccine regimen for practical use in animal
      health.

PMID- 16098639
TI  - Salmonella typhimurium grown in iron-rich media, inactivated with ferric chloride
      and adjuvanted with homologous bacterial DNA is potent and efficacious vaccine in
      mice.
AB  - The present study describes our attempt to construct a novel vaccine formulation
      that affords full protection against murine typhoid under experimental
      conditions. Ferric chloride, 100mM, as inactivating agent, bacterial growth under
      iron-rich conditions and homologous bacterial DNA as adjuvant were used for
      construction of the experimental Salmonella typhimurium vaccine. The vaccine
      inoculated twice at 2 weeks interval in Swiss albino mice elicited statistically
      significant IgG levels when compared with non-adjuvanted and other control
      groups. All the mice inoculated with the novel vaccine withstood challenge with
      50 LD(50) dose of S. typhimurium strain St 585. No significant safety problems
      were found in mice.

PMID- 16098640
TI  - Expression profiles of inflammatory and immune-related genes in Atlantic salmon
      (Salmo salar L.) at early time post vaccination.
AB  - Vaccination of Atlantic salmon parr with oil-based vaccines will inevitably cause
      inflammation at the site of injection, albeit the underlying mechanisms are not
      very well understood or studied in any detail. Here, we report time-course
      changes in expression levels, assessed by real-time RT-PCR of IL-1 beta, Mx, two
      beta-2-microglobulin variants and MHC class II beta, from 2 to 19 days post
      vaccination with a multi-component oil-adjuvanted vaccine. Highly variable
      individual responses to vaccination make selection of high responders essential
      prior to subtractive analysis. Based on the above mentioned expression profiles,
      high-responding individuals at 2, 8 and 19 days post vaccination, were selected
      for subtractive analysis. Clustering of clones according to putative function,
      suggest an initial up-regulation of genes involved in metabolism and cell
      signalling, before onset of genes involved in inflammation. The lag-time for
      genes considered as inflammatory markers was more than 48 h, while they were
      found to constitute the major part of up-regulated transcripts by 8 days post
      vaccination. By day 19, immune-related genes like immunoglobulin and T cell
      receptor genes, comprised a higher proportion of the up-regulated genes than at
      earlier time points.

PMID- 16098641
TI  - Death following hexavalent vaccination.

PMID- 16098642
TI  - Concentration levels of 210Pb and 210Po in dry tobacco leaves in Greece.
AB  - Tobacco leaves are large and have sticky exudates that retain the radon decay
      products once they deposit on the leaves. The study of 210Po in tobacco is
      required, because of the cumulative alpha-radiation dose delivered to humans from
      inhaled 210Po in cigarette smoke. 210Pb is the other element of interest since it
      is the 210Po precursor in the radioactive decay chain. In the present study, the
      concentrations of these two radionuclides were determined in tobacco samples from
      seven regions in Greece. 210Po was determined by alpha spectrometry using a
      surface barrier detector after radiochemical separation and spontaneous
      deposition of polonium on a nickel disk. The 210Pb activity in the samples was
      determined via the 210Po resulting from the decay of 210Pb. The results of the
      present study indicate that 210Po concentrations ranged from 3.6 to 17.0 mBqg(-1)
      (average 13.1 mBqg(-1)) of dry tobacco, while 210Pb concentrations ranged from
      7.3 to 18.0 mBqg(-1) (average 13.4 mBqg(-1)). The mean value of the annual
      committed effective dose for smokers (20 cigarettes per day) of Greek tobacco was
      estimated to be 287 microSv (124 microSv from 210Po and 163 microSv from 210Pb).
      The inhalation dose for smokers is on average about 12 times higher than for non
      smokers living in the mid-latitudes of the northern hemisphere.

PMID- 16098643
TI  - Natural radioactivity in Brazilian groundwater.
AB  - More than 220 groundwater samples were analyzed for 228Ra, 226Ra, 222Rn, 210Pb,
      U(nat), Th(nat), pH, conductivity, fluoride and some additional elements
      determined by ICP-MS. Since samples from several Brazilian states were taken,
      involving areas with quite different geologies, no general trend was observed
      relating the chemical composition and the natural radionuclide content. On the
      other hand, 210Pb strongly depends on the water content of its progenitor, 222Rn.
      The values obtained during the present work were compared with those reported by
      Hainberger et al. [Hainberger, P.L., de Oliveira Paiva, I.R., Salles Andrade,
      H.A., Zundel, G., Cullen, T.L., 1974. Radioactivity in Brazilian mineral waters.
      Radiation Data and Reports, 483-488.], when more than 270 groundwater samples
      were analyzed, mainly, for 226Ra. Based on the results of both works, it was
      possible to build a database including the results of both works, generating a
      set with the radium content of circa 350 groundwater sources. It was demonstrated
      that 228Ra, 226Ra, 222Rn, 210Pb and U(nat) content in Brazilian groundwater
      follows a lognormal distribution and the obtained geometric mean were 0.045,
      0.014, 57.7, 0.040 BqL(-1) and 1.2 microgL(-1), respectively.

PMID- 16098644
TI  - Evaluation of the effect of collagen network degradation on the frictional
      characteristics of articular cartilage using a simultaneous analysis of the
      contact condition.
AB  - BACKGROUND: Superficial conditions and integrity of collagen network play an
      important role on the lubrication performance of articular cartilage. In this
      work, a technique based on the evanescent waves is used for the evaluation of
      contact condition during friction tests. METHODS: The frictional and superficial
      characteristics of the normal and degraded articular cartilages with high and low
      concentration of collagenase were evaluated. The optical apparatus was set in
      order to decrease the intensity of a light reflected at the interface between a
      prism and specimens when collagen fibers are found near the interface. FINDINGS:
      For all conditions, an increase in the attenuation of reflectance as the friction
      coefficient increases was observed with reasonable correlation. For the specimens
      degraded with collagenase, low friction and reduced attenuation of reflectance
      were observed at the beginning of sliding followed by a gradual increase in both
      friction and attenuation of reflectance. In comparison to the degraded specimens,
      normal specimens presented high friction at beginning and low friction at the end
      of test. INTERPRETATION: The superficial conditions and the presence of water at
      the articular surface play an important role in the lubrication of synovial
      joints. The ability to retain water for degraded specimens is impaired due to the
      loss of proteoglycan observed in the histological sections and hence, their low
      friction observed at the beginning of the test is not sustained for a long time.
      The use of evanescent waves demonstrated to be very useful in the analysis of the
      contact condition of articular cartilage.

PMID- 16098645
TI  - Angular position, range of motion and velocity of arm elevation: a study of
      consistency of performance.
AB  - BACKGROUND: To define the normal range, velocity and consistency of the movement
      of active arm elevation with humerus in neutral or in external rotation using a
      simplified kinematic model. METHODS: Nine normal volunteers and the non-involved
      side of twenty five patients with unilateral shoulder lesion participated. A 3D
      optoelectronic tracking system was used to register the movement of raising the
      arm from the normal upright position to maximal elevation in a repetitive way.
      Peak humeral position, range of movement, velocity of motion and consistency of
      cycles were analyzed. Descriptive statistics, correlation between variables and
      with sex, age and side are presented, including differences between performances
      of movement done in neutral or external rotation. FINDINGS: Data of the six
      variables were: maximal abduction 142 degrees [137.4-147.0], range of motion
      118.1 degrees [112-124], maximal velocity 238 degrees/s [209-265]; mean velocity
      113 degrees/s [96-130]; coefficient of variation of maximal angular abduction was
      2.2% [1.7-2.7]; coefficient of variation of maximal velocity 8.6% [7.3-9.9]. No
      significant differences were observed either on side, sex or between the shoulder
      of normal volunteers or that of the patients with opposite shoulder lesions.
      Participants older than 45 years old showed only a significant slightly lower
      average velocity. The study confirms the weak association between dependent
      (biomechanical) and independent variables. INTERPRETATION: As it is described
      here, analysis of arm elevation has not been previously studied and shows that
      has a good consistency in angular position, velocity and repeatability of motion
      in normal conditions which permits a picture of the overall performance of the
      shoulder.

PMID- 16098646
TI  - The influence of static axial torque in combined loading on intervertebral joint
      failure mechanics using a porcine model.
AB  - BACKGROUND: The spine is routinely subjected to repetitive combined loading,
      including axial torque. Repetitive flexion-extension motions with low magnitude
      compressive forces have been shown to be an effective mechanism for causing disc
      herniations. The addition of axial torque to the efficacy of failure mechanisms,
      such as disc herniation, need to be quantified. The purpose of this study was to
      determine the role of static axial torque on the failure mechanics of the
      intervertebral joint under repetitive combined loading. METHODS: Repetitive
      flexion-extension motions combined with 1472 N of compression were applied to two
      groups of nine porcine motion segments. Five Nm of axial torque was applied to
      one group. Load-displacement behaviour was quantified, and planar radiography was
      used to document tracking of the nucleus pulposus and to identify fractures.
      FINDINGS: The occurrence of facet fractures was found to be higher (P=0.028) in
      the axial torque group (7/9), compared to the no axial torque group (2/9). More
      hysteresis energy was lost up to 3000 cycles of loading in the axial torque group
      (P<0.014). The flexion-extension cycle stiffness was not different between the
      two groups until 4000 cycles of loading, after which the axial torque group
      stiffness increased (P=0.016). The percentage of specimens that herniated after
      3000 cycles of loading was significantly larger (P=0.049) for the axial torque
      group (71%) compared to the no axial torque group (29%). INTERPRETATION: Small
      magnitudes of static axial torque alter the failure mechanics of the
      intervertebral disc and vertebrae in combined loading situations. Axial torque
      appears to accelerate the susceptibility for injury to the intervertebral joint
      complex. This suggests tasks involving axial torque with other types of loading,
      apart from axial twist motion, should be monitored to assess exposure and injury
      risk.

PMID- 16098647
TI  - Tradescantia micronucleus test indicates genotoxic potential of traffic emissions
      in European cities.
AB  - Urban atmospheres contain complex mixtures of air pollutants including mutagenic
      and carcinogenic substances such as benzene, diesel soot, heavy metals and
      polycyclic aromatic hydrocarbons. In the frame of a European network for the
      assessment of air quality by the use of bioindicator plants, the Tradescantia
      micronucleus (Trad-MCN) test was applied to examine the genotoxicity of urban air
      pollution. Cuttings of Tradescantia clone #4430 were exposed to ambient air at 65
      monitoring sites in 10 conurbations employing a standardised methodology. The
      tests revealed an elevated genotoxic potential mainly at those urban sites which
      were exposed to severe car traffic emissions. This bioassay proved to be a
      suitable tool to detect local 'hot spots' of mutagenic air pollution in urban
      areas. For its use in routine monitoring programmes, however, further
      standardisation of cultivation and exposure techniques is recommended in order to
      reduce the variability of results due to varying environmental conditions.

PMID- 16098648
TI  - Pathways to suicidal behaviour among adolescent girls in Nicaragua.
AB  - Adolescent girls are the most frequent suicide attempters worldwide. However,
      there is little knowledge about pathways leading to suicidal behaviour among
      young people, in particular in low-income countries. This study explores the
      motives and processes related to suicidal behaviour among young girls in
      Nicaragua. Individual in-depth interviews were conducted with eight girls aged
      between 12 and 19 admitted to hospital after attempting suicide. The audio-taped
      interviews lasted 2-4 h and were transcribed, translated into English and coded
      for content. Grounded theory and content analysis were used to construct a theory
      of the mechanisms behind their suicidal behaviour. A tentative model exploring
      pathways to suicidal behaviour is described with four main categories:
      structuring conditions, triggering events, emotions and actions taken. The model
      illustrates the dialectic interplay between structure and actions taken. Actions
      taken were categorized as problem solving or various forms of escape where
      failure with either of these strategies resulted in a suicide attempt.
      Dysfunctional families, absent fathers and lack of integration into society were
      some of the structuring conditions that lead to emotional distress. Abuse, deaths
      in the family, break-up with boyfriends or suicide among friends acted as
      triggering events. A striking finding was the obvious narrative competence of the
      girls. Our findings indicate that suicide prevention programmes for young people
      must offer support from professionals, independent of their family and social
      networks. Institutions in the community in contact with young people with
      suicidal behaviour must develop communicative skills to offer a trusting
      environment mobilising the resources that young people have.

PMID- 16098649
TI  - Cross-national variation of gender differences in adolescent subjective health in
      Europe and North America.
AB  - The cross-national consistency and variation of gender differences in subjective
      health complaints was examined in a sample of 125732 11- to 15-year-olds from 29
      European and North American countries, participating in the WHO collaborative
      study 'Health behaviour in school-aged children (HBSC) 1997/98'. Health
      complaints were measured with the Health Behaviour in School-aged Children
      Symptom Checklist. Gender differences in health complaints were analysed through
      multilevel logistic regression analysis. The results indicated a very robust
      pattern of increasing gender differences across age, with 15-year-old girls as a
      group at increased risk for health complaints across all countries. The magnitude
      of gender differences varied across countries, with some countries showing a
      consistently strong gender difference across age group and different health
      complaints, and other countries showing a consistently weak gender difference.
      The gender difference in health complaints was stronger in countries with a low
      gender development index score. The findings underscore the need to incorporate
      socio-contextual factors in the study of gender health inequalities during
      adolescence.

PMID- 16098650
TI  - Psychosocial work conditions, social participation and social capital: a causal
      pathway investigated in a longitudinal study.
AB  - Social capital is often claimed to be promoted by stable social structures such
      as low migration rates between neighbourhoods and social networks that remain
      stable over time. However, stable social structures may also inhibit the
      formation of social capital in the form of social networks and social
      participation. One example is psychosocial conditions at work, which may be
      determined by characteristics such as demand and control in the work situation.
      The study examines the active workforce subpopulation within the Swedish Malmo
      Shoulder Neck Study. A total of 7836 individuals aged 45-69 years, were
      interviewed at baseline between 1992 and 1994, and at a 1-year follow-up. Four
      groups of baseline psychosocial work conditions categories defined by the Karasek
      Theorell model (jobstrain, passive, active, relaxed) were analysed according to
      13 different social participation items during the past year reported at the 1
      year follow-up. Odds ratios and 95% confidence intervals with the jobstrain group
      as a reference were estimated. A multivariate logistic regression model was used
      to assess differences in different aspects of social participation between the
      four psychosocial work conditions groups. The results show that the respondents
      within the active category in particular but also the relaxed category, have
      significantly higher participation in many of the 13 social participation items,
      even after multivariate adjustments. The results strongly suggest that
      psychosocial work conditions may be an important determinant of social capital
      measured as social participation, a finding of immediate public health relevance
      because of the well known positive association between social participation and
      health-related behaviours.

PMID- 16098651
TI  - Rapid categorization of foveal and extrafoveal natural images: associated ERPs
      and effects of lateralization.
AB  - Humans are fast and accurate at performing an animal categorization task with
      natural photographs briefly flashed centrally. Here, this central categorization
      task is compared to a three position task in which photographs could appear
      randomly either centrally, or at 3.6 degrees eccentricity (right or left) of the
      fixation point. A mild behavioral impairment was found with peripheral stimuli
      with no evidence in support of hemispheric superiority; but enlarging the window
      of spatial attention to three possible stimuli locations had no behavioral cost
      on the processing of central images. Performance in the central categorization
      task has been associated with a large difference between the potentials evoked to
      target and non-target correct trials, starting about 150 ms after stimulus onset
      on frontal sites. Present results show that this activity originates within
      extrastriate visual cortices and probably reflects perceptual stimuli differences
      processed within areas involved in object recognition. Latencies, slopes, and
      peak amplitudes of this differential activity were invariant to stimulus position
      and attentional load. Stimulus location uncertainty and lateralization did not
      affect speed of visual processing.

PMID- 16098652
TI  - Medical management of incidents with chemical warfare agents.
AB  - Successful management of incidents with chemical warfare agents strongly depends
      on the speed of medical help and the ability of helpers to react properly. Though
      the general principles of clinical toxicology, such as decontamination,
      stabilization, patient evaluation and symptomatic treatment are similar for many
      toxicants, chemical warfare agents deserve special attention because of their
      very high inhalative and cutaneous toxicity, rapid onset of the disease and
      multiple organ failures. This article describes the medical management of mass
      casualties with blister agents, nerve agents and blood agents from the viewpoint
      of a clinical toxicologist. Characteristic diagnostic signs, decontamination
      procedures and therapeutic schemes for these agents are described. Treatment
      options are discussed. The importance of planning (e.g. antidote availability)
      and preparedness is emphasized.

PMID- 16098653
TI  - Aluminium-induced deterioration in reproductive performance and seminal plasma
      biochemistry of male rabbits: protective role of ascorbic acid.
AB  - Aluminium (Al) has been proposed as an environmental factor that may contribute
      to some diseases, affect several enzymes and other biomolecules and induced free
      radical-mediated cytotoxicity. Also, Al induced reproductive toxicity and exerted
      a significant adverse effect on the steroidogenesis. The antioxidant ascorbic
      acid (AA) plays an important role in various physiological processes in the body
      including detoxification of different toxic materials. Therefore, the present
      investigation aimed to elucidate possible protective effects of AA in alleviating
      the toxicity of aluminium chloride (AlCl3) on reproductive performance, lipid
      peroxidation and enzyme activities in seminal plasma of male New Zealand white
      rabbits. Six rabbits per group were assigned to one of four treatment groups: 0
      mg AA and 0 mg AlCl3 /kg body weight (BW) (control); 40 mg AA/kg BW; 34 mg AlCl3
      /kg BW; 34 mg AlCl3 plus 40 mg AA/kg BW. Rabbits were orally administered their
      respective doses every other day for 16 weeks. Results obtained showed that AlCl3
      significantly (P<0.05) decreased libido (by increasing the reaction time),
      ejaculate volume, sperm concentration, total sperm output, sperm motility (%),
      total motile sperm per ejaculate (TMS), packed sperm volume (PSV), total
      functional sperm fraction (TFSF), normal and live sperm and semen initial
      fructose. While initial hydrogen ion concentration (pH) and dead and abnormal
      sperm were increased (P<0.05). Live body weight (LBW), feed intake (FI) and
      relative weights of testes (RTW) and epididymis (REW) were significantly (P<0.05)
      decreased. Concentrations of thiobarbituric acid-reactive substances (TBARS) were
      significantly (P<0.05) increased in seminal plasma of rabbits treated with AlCl3
      compared with control. While, activities of glutathione S-transferase (GST),
      aspartate aminotransferase (AST), alanine aminotransferase (ALT) and acid
      phosphatase (AcP) were significantly (P<0.05) decreased. Ascorbic acid alone
      significantly increased LBW, FI, RTW, REW, semen characteristics and seminal
      plasma enzymes, and decreased the levels of free radicals. Also, the present
      study showed that ascorbic acid might be effective in the protection of aluminium
      induced reproductive toxicity. It was suggested that AlCl3 exerted a significant
      adverse effect on reproductive performance of male rabbits. Furthermore, AA could
      be able to antagonize the toxic effects of AlCl3 and improved semen quality of
      male rabbit.

PMID- 16098654
TI  - In hospital cardiac arrest: missing links in the chain of survival.

PMID- 16098655
TI  - Sex differences in the interleukin-6 response to acute psychological stress.
AB  - Interleukin-6 (IL-6), an immune regulator that helps coordinate the inflammatory
      response, may mediate inflammatory disease exacerbation associated with stress.
      Twenty men and twenty women completed a single session, comprising baseline (20
      min), mental arithmetic task (8 min), and recovery (60 min). Blood samples, taken
      at baseline, immediately after the task, and at +30 and +60 min recovery were
      analysed for plasma IL-6. Overall, IL-6 increased linearly from baseline to +60
      min recovery, and a sex difference was found in the IL-6 response, with men
      peaking earlier than women. These findings confirm a small delayed IL-6 increase
      after acute laboratory stress, and reveal sex differences in the profile of the
      IL-6 response.

PMID- 16098656
TI  - Preliminary atomic force microscopy study of two-dimensional crystals of lactose
      permease from Escherichia coli.
AB  - Lactose permease (LacY) of Escherichia coli is not only a paradigm for secondary
      transporters but also for difficulties in two-dimensional (2D) crystallization.
      In this work we present the progresses achieved in the observation of 2D crystals
      of wild-type LacY by atomic force microscopy (AFM). Crystals were obtained
      following reconstitution of LacY in 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) liposomes. Proteolipid sheets (PLSs) 6.4 nm in height were
      obtained after spreading the samples onto mica. Observations were carried out in
      liquid medium and in contact mode (CM-AFM). When the crystalline surfaces of the
      PLSs were imaged regular packing arrangements were observed. The back-Fourier
      transformation revealed the existence of various orientations mostly consistent
      with crystals possessing p2 symmetry and unit-cell dimensions: a=13.15 nm,
      b=16.74 nm, gamma=116 degrees. The characteristics, size, and shape of the
      repetitive motif could be compatible with dimers of this protein. These
      preliminary results are compared and discussed with previously reported 2D
      crystals observed by electron microscopy.

PMID- 16098657
TI  - Perfusion CT investigation of chronic internal carotid artery occlusion:
      comparison with SPECT.
AB  - This study investigated the usefulness of perfusion computed tomography (CT) for
      the evaluation of patients with chronic internal carotid artery (ICA) occlusion
      by comparing the findings with those of iodine-123 iodoamphetamine ([(123)I]IMP)
      single photon emission computed tomography (SPECT). Twenty five patients with
      chronic ICA occlusion were investigated on the same day by perfusion CT to
      measure the cerebral blood flow (CBF), cerebral blood volume (CBV), and mean
      transient time (MTT), and [(123)I]IMP SPECT to measure the regional CBF,
      significant correlations were observed between regional CBF measured by SPECT and
      CBF measured by perfusion CT (r = 0.659, R(2) = 0.434, p < 0.001), regional CBF
      and CBV (r = -0.406, R(2) = 0.165, p < 0.001) and regional CBF and MTT (r = 
      0.592, R(2) = 0.350, p < 0.001). Significant correlations were also observed
      between CBF and CBV (r = -0.153, R(2) = 0.023, p < 0.001), CBF and MTT (r = 
      0.580, R(2) = 0.337, p < 0.001) and MTT and CBV (r = 0.763, R(2) = 0.582, p <
      0.001). Perfusion CT is useful to evaluate the hemodynamic state of patients with
      chronic major cerebral artery occlusive disorders.

PMID- 16098658
TI  - Tumor suppressive effects of tocotrienol in vivo and in vitro.
AB  - Tocotrienols have been reported to have higher biological activities than
      tocopherols. We investigated the antitumor effect of tocotrienols both in vivo
      and in vitro. Oral administration of tocotrienols resulted in significant
      suppression of liver and lung carcinogenesis in mice. In human hepatocellular
      carcinoma HepG2 cells, delta-tocotrienol exerted more significant
      antiproliferative effect than alpha-, beta-, and gamma-tocotrienols. delta
      Tocotrienol induced apoptosis, and also tended to induce S phase arrest. On the
      other hand, gene expression analysis showed that delta-tocotrienol increased
      CYP1A1 gene, a phase I enzyme. Although further study will be necessary to
      investigate possible adverse effect, the data obtained in present study suggest
      that tocotrienols could be promising agents for cancer prevention.

PMID- 16098659
TI  - Adsorption of boron from aqueous solutions using fly ash: batch and column
      studies.
AB  - In the present paper, boron removal from aqueous solutions by adsorption was
      investigated. Fly ash particle size used in adsorption experiments was between
      250 and 400 microm. During the experimental part of this study, the effect of
      parameters such as pH, agitation time, initial boron concentration, temperature,
      adsorbent dosage and foreign ion on boron removal were observed. In addition,
      adsorption kinetics, adsorption isotherm studies and column studies were made.
      Maximum boron removal was obtained at pH 2 and 25 degrees C. Thermodynamic
      parameters such as change in free energy (DeltaG degrees), enthalpy (DeltaH
      degrees), entropy (DeltaS degrees) were also determined. As a result of the
      kinetic studies, it was observed that the adsorption data conforms to the second
      degree kinetics model. In the isotherm studies, Langmuir and Freundlich isotherm
      models were applied and it was determined that the experimental data conformed to
      Langmuir isotherm model. Batch adsorbent capacity (q(o)) was calculated as 20.9
      mg/g. The capacity value for column study was obtained by graphical integration
      as 46.2 mg/g. The Thomas and the Yoon-Nelson models were applied to experimental
      data to predict the breakthrough curves and to determine the characteristics
      parameters of the column useful for process design.

PMID- 16098660
TI  - Hexavalent chromium removal by ferrochromium slag.
AB  - The aim of this study is to demonstrate the potential of Cr(VI) generation during
      jigging operation applied for ferrochrome recovery from slag. The Cr(VI)
      concentrations of water contacted with ferrochromium slag (W/FS=10) in a closed
      cycle after 50 batches were found as 0.61 mg/l. Also, reduction of Cr(VI) to
      Cr(III) and a subsequent precipitation of Cr(III) by using ferrochrome slag (FS)
      in a model solution has been aimed. The effects of amount of acid, contact time,
      FS dosage, initial Cr(VI) concentration and temperature on the Cr(VI) reduction
      have been studied through the batch runs. The amount of acid has been found to be
      the most effective parameter affecting the Cr(VI) reduction. A 10 g/l FS dosage
      and 3.5 ml/l H2SO4 (5M) are sufficient to reduce all Cr(VI) in the model solution
      containing 10mg/l Cr(VI) and for contact time of 60 min at 25 degrees C. In
      reduced solutions, precipitation of metal ions has been studied by using extra
      FS. A 60 g/l dosage of fresh FS can precipitate all Cr(III) and Fe ions in the
      reduced solution. Thus, it has been demonstrated that the treatment of jigging
      water stream to be generated in a ferrochrome plant containing Cr(VI) can be
      accomplished by using ferrochromium slag and sulphuric acid. Also, it has been
      determined that solid residues of the process are environmentally stable by
      applying TCLP test.

PMID- 16098661
TI  - Reactive oxygen species and p38 phosphorylation regulate the protective effect of
      Delta9-tetrahydrocannabinol in the apoptotic response to NMDA.
AB  - NMDA causes oxidative stress in neurons, and produces cell death involving
      elements of both necrosis and apoptosis. To examine the neuroprotective mechanism
      of Delta9-tetrahydrocannabinol (THC) in NMDA-induced death of AF5 cells, we
      measured reactive oxygen species (ROS) formation after exposure to NMDA. ROS
      generation was increased by NMDA, and NMDA-induced ROS generation was
      significantly decreased by THC. Western blotting revealed an increase in
      phosphorylated p38 MAPK after NMDA treatment, which was also blocked by
      pretreatment with THC. The time course of ROS generation and activation of MAPK
      signaling pathways were similar. SB203580, a p38 inhibitor, partially blocked
      glutamate excitotoxicity in AF5 cells. The present data suggest that THC protects
      against NMDA-induced apoptosis in AF5 cells by blocking ROS generation and
      inhibiting the activation of p38-MAPK.

PMID- 16098662
TI  - The impact of ethnic differences in response to capsaicin-induced trigeminal
      sensitization.
AB  - Ethnic differences in the experience of pain, pain-related health care
      utilization and pain-reducing activities have been reported. Thus, evaluating of
      such variations is important in clinical and experimental pain. Since clinical
      pain is greatly influenced by disease-specific factors (severity, duration, type
      and treatment), evaluating ethnic differences in experimental pain models may not
      only provide some information about underlying mechanisms but also may predict or
      explain group differences in clinical pain. Migraine prevalence within ethnic
      populations is varied. Capsaicin injection to the forehead of healthy volunteers
      induces the state of an experimental trigeminal sensitization, which is one of
      the proposed mechanisms of migraine. The aim of the present study was to
      investigate ethnic differences between Caucasians and South Indians in this model
      of trigeminal sensitization. Thirty-two healthy male volunteers (16 South Indians
      and 16 Danish Caucasians) were included. Capsaicin (100 microg/0.1 ml) was
      injected intradermally to the right forehead skin. Pain sensitivity, secondary
      hyperalgesic area, and pressure pain threshold were assessed. Overall, the model
      showed significant greater pain responses in South Indians (8.75+/-1.25 cm pain
      intensity and 9.33+/-2.32 cm2 hyperalgesic area) compared to Caucasians (6.25+/
      1.95 cm pain intensity and 6.25+/-1.41 cm2 hyperalgesic area). The model may
      provide important information for further clinical research, e.g. migraine or
      differences in mechanisms underlying trigeminal sensitization.

PMID- 16098663
TI  - Central cyclooxygenase inhibitors reduced IL-1beta-induced hyperalgesia in
      temporomandibular joint of freely moving rats.
AB  - Microinjection of formalin (5%, 50 microl) into a temporomandibular joint (TMJ)
      causes noxious behavioral responses in freely moving rats. In the present study,
      we investigated the role of central cyclooxygenase (COX) pathways in IL-1beta
      induced hyperalgesia with formalin-induced TMJ pain model. Intra-articular
      injection of 100 pg or 1 ng of IL-1beta significantly facilitated formalin
      induced behavior by 130 or 174% in the number of scratches. Intracisternal
      administration of 100 pg or 1 ng of IL-1beta also significantly increased
      formalin-induced behavior by 166 or 82% in the number of scratches. IL-1beta
      induced hyperalgesia was blocked by pretreatment with IL-1 receptor antagonist.
      Intracisternal pretreatment with SC-560, a selective COX-1 inhibitor, or NS-398,
      a selective COX-2 inhibitor, abolished intra-articular administration of IL-1beta
      induced hyperalgesic response. Intracisternal pretreatment with NS-398, a
      selective COX-2 inhibitor, abolished the intracisternal administration of IL
      1beta-induced hyperalgesic response, while pretreatment with SC-560, a selective
      COX-1 inhibitor, did not change IL-1beta-induced hyperalgesic responses. On the
      other hand, pretreatment with acetaminophen, a tentative COX-3 inhibitor, also
      abolished both intra-articular and intracisternal administration of IL-1beta
      induced hyperalgesic responses. These results indicate that central COX-2 plays
      important role in the central administration of IL-1beta-induced hyperalgesia and
      that central COX-1/2 pathways mediate peripheral administration of IL-1beta
      induced hyperalgesia in the TMJ. Central COX-3 inhibitor seems to play an
      important role in the nociceptive process associated with both peripheral and
      central administration of IL-1beta-induced hyperalgesia in TMJ. It is concluded
      that central acting of COX-3 inhibitors may be of therapeutic value in the
      treatment of inflammatory pain in TMJ.

PMID- 16098664
TI  - Tactile allodynia in patients with postherpetic neuralgia: lack of change in skin
      blood flow upon dynamic stimulation.
AB  - Tactile allodynia is a common, troublesome feature of neuropathic pain. Allodynia
      has been proposed to involve abnormal Abeta-afferent coupling in the dorsal horn
      resulting in C-fibre activation and increased skin blood flow (SBF). Thus,
      changes in SBF could provide an objective measure of allodynia. We searched for
      this mechanism in patients with postherpetic neuralgia (PHN) with varying degrees
      of cutaneous sensory loss. We mapped the allodynic area in PHN patients using
      cotton buds and von Frey hairs. Quantitative thermal testing was performed to
      assess small fibre function in the affected and mirror-image areas. At a
      subsequent visit the area of allodynia was remapped. Then the SBF in the affected
      and control areas was quantified before and after allodynic stimulation using
      laser Doppler imaging and subsequent single point continuous monitoring to detect
      rapid changes. We enrolled 10 PHN patients (medians: age 77 yrs, duration 20
      months, ongoing pain 5). The allodynic area (range 11-546 cm2) was stable across
      the sessions. Thermal testing showed similar (n=5) or reduced (n=5) warmth and
      pain sensation in the affected versus control area. Following allodynic
      stimulation (median evoked pain-5) we saw no changes in SBF using either imaging
      (repeated measures ANOVA, P=0.73) or single point monitoring. This was the case
      for all patients regardless of the degree of sensory impairment in the affected
      dermatome. In conclusion, in a representative population of PHN patients we found
      no evidence of changes in SBF in response to allodynic stimulation. Hence, SBF
      measurements are not suitable for assessing allodynia.

PMID- 16098665
TI  - Neuropathological findings after continuous intrathecal administration of S(+)
      ketamine for the management of neuropathic cancer pain.
AB  - Questions have been raised about the potential neurotoxicity of the neuraxial use
      of ketamine although ketamine and its active enantiomer S(+)-ketamine have been
      used intrathecally and epidurally (caudally) for the management of perioperative
      pain and in a variety of chronic pain syndromes. Clinical experience following
      neuraxial administration of S(+)-ketamine has been documented without reference
      to local central nervous system toxicity following this approach. In addition,
      there are no preclinical safety data regarding stability, compatibility, and
      neurotoxicity on intrathecal use of single S(+)-ketamine or combinations of S(+)
      ketamine, morphine, bupivacaine, and clonidine. In the present case, the
      continuous intrathecal administration of S(+)-ketamine, in combination with
      morphine, bupivacaine, and clonidine resulted in adequate pain relief in a
      patient suffering from intractable neuropathic cancer pain. However, postmortem
      observation of the spinal cord and nerve roots revealed severe histological
      abnormalities including central chromatolysis, nerve cell shrinkage,
      neuronophagia, microglial upregulation, and gliosis. Based on our results,
      neuraxial administration of S (+)-ketamine cannot be recommended for clinical
      practise before a systematic study of toxicology of neuraxial S(+)-ketamine in
      animals or humans has been performed.

PMID- 16098667
TI  - Molecular and behavioral changes in nociception in a novel rat model of chronic
      pancreatitis for the study of pain.
AB  - The approach to the management of painful chronic pancreatitis has been
      empirical, primarily due to the lack of information about biological mechanisms
      producing pain. To facilitate research into pain mechanisms, our aim was to
      assess a rat model of chronic pancreatitis induced by pancreatic infusion of
      trinitrobenzene sulfonic acid as a model of painful pancreatitis. Nociception was
      assessed by measuring mechanical sensitivity of the abdomen and by recording the
      number of nocifensive behaviors in response to electrical stimulation of the
      pancreas. Expression of neuropeptides calcitonin gene-related peptide (CGRP) and
      substance P (SP) in the thoracic dorsal root ganglia receiving input from the
      pancreas and nerve growth factor (NGF) in the pancreas were measured. Rats with
      pancreatitis exhibited marked increase in sensitivity to mechanical probing of
      the abdomen and increased sensitivity to noxious electrical stimulation of the
      pancreas. There were significant increases in NGF protein in the pancreas and in
      expression of neuropeptides CGRP and SP in the sensory neurons from dorsal root
      ganglia receiving input from the pancreas. We have established quantitative
      measures of referred nociception and pancreatic hyperalgesia in a rat model of
      chronic pancreatitis that bears histological similarities to the human disease.
      This model has considerable construct, face and predictive validity for the human
      condition. It is of importance for the study of the pathogenesis of pain in this
      condition and can facilitate the development of new therapeutic options.

PMID- 16098668
TI  - Peripheral axonal injury results in reduced mu opioid receptor pre- and post
      synaptic action in the spinal cord.
AB  - In both the spared nerve injury (SNI) and spinal nerve ligation (SNL) rat
      peripheral neuropathic pain models the presynaptic inhibitory effect of the mu
      opioid receptor (MOR) agonist (DAMGO) on primary afferent-evoked excitatory
      postsynaptic currents (EPSCs) and miniature EPSCs in superficial dorsal horn
      neurons is substantially reduced, but only in those spinal cord segments
      innervated by injured primary afferents. The two nerve injury models also reduce
      the postsynaptic potassium channel opening action of DAMGO on lamina II spinal
      cord neurons, but again only in segments receiving injured afferent input. The
      inhibitory action of DAMGO on ERK (extracellular signal-regulated kinase)
      activation in dorsal horn neurons is also reduced in affected segments following
      nerve injury. MOR expression decreases substantially in injured dorsal root
      ganglion neurons (DRG), while intact neighboring DRGs are unaffected. Decreased
      activation of MOR on injured primary afferent central terminals and the second
      order neurons they innervate may minimize any reduction by opioids of the
      spontaneous pain mediated by ectopic input from axotomized small diameter
      afferents. Retention of MOR expression and activity in nearby non-injured
      afferents will enable, however, an opioid-mediated reduction of stimulus-evoked
      and spontaneous pain carried by intact nociceptor afferents and we find that
      intrathecal DAMGO (1000 ng) reduces mechanical hypersensitivity in rats with SNL.
      Axotomy-induced changes in MOR may contribute to opioid- insensitive components
      of neuropathic pain while the absence of these changes in intact afferents may
      contribute to the opioid sensitive components.

PMID- 16098669
TI  - Comment on: A role for the brainstem in central sensitization in humans. Evidence
      from functional magnetic resonance imaging. Zambreanu et al. Pain 2005;114:397
      407.

PMID- 16098670
TI  - The case for the inclusion of female subjects in basic science studies of pain.

PMID- 16098671
TI  - Pronociceptive role of peripheral and spinal 5-HT7 receptors in the formalin
      test.
AB  - The possible pronociceptive role of peripheral and spinal 5-HT7 receptors in the
      formalin test was assessed. Local administration of 5-HT7 (SB-269970, 2.5-77.1
      nmol/paw), but not 5-HT(1A) (WAY-100635, 1-60 nmol/paw), receptor antagonist
      significantly reduced formalin-induced flinching. Local 5-hydroxytryptamine (5
      HT, 3-100 nmol/paw) or 5-carboxamidotryptamine (5-CT, 0.3-3 nmol/paw) (a 5-HT7/1A
      receptor agonist) augmented, in a dose-dependent manner, 0.5% formalin-induced
      nociceptive behavior. The local pronociceptive effect of 5-HT or 5-CT was
      significantly reduced by SB-269970 (25 and 77.1 nmol/paw), but not by WAY-100635
      (10 nmol/paw). 5-HT7 receptors were observed in myelinated and unmyelinated axons
      of the digital nerves in rat hindpaw. Intrathecal SB-269970 (2.5-77.1 nmol/rat)
      or WAY-100635 (1-50 nmol/rat) did not modify 1% formalin-induced nociceptive
      behavior. Spinal 5-HT (25-200 nmol/rat) significantly reduced formalin-induced
      flinching behavior during phase 2. At lower doses (0.1-3 nmol/rat) intrathecal 5
      CT dose-dependently increased flinching during phase 2. In contrast, higher doses
      (10-30 nmol/rat) of 5-CT reduced formalin-induced nociceptive behavior during
      both phases. The spinal pronociceptive effect of 5-CT was reduced by SB-269970
      (7.7-77 nmol/rat), but not by WAY-100635 (10 nmol/rat). In addition, the spinal
      antinociceptive effect of 5-CT was partially reversed by WAY-100635 (10
      nmol/rat). The spinal antinociceptive effect of 5-HT was unaffected either by SB
      269970 (77 nmol/rat) or WAY-100635 (10 nmol/rat). Data suggest that 5-HT7, but
      not 5-HT1A, receptors play a pronociceptive role in peripheral and spinal sites
      in the rat formalin test.

PMID- 16098674
TI  - Comparison of proteome and antigenic proteome between two Neospora caninum
      isolates.
AB  - This study was conducted to explore the relationship between two isolates of
      Neospora caninum (N. caninum) (KBA-2 and VMDL-1) using proteomics. To achieve the
      goal, proteins of N. caninum tachyzoite lysates of KBA-2 and VMDL-1 were
      separated by two-dimensional gel electrophoresis (2-DE), stained with silver
      nitrate and analyzed using matrix-assisted laser desorption/ionization-time of
      flight mass spectrometry (MALDI-TOF MS) to compare protein profiles. In addition,
      proteins separated by 2-DE were transferred to membranes, probed with bovine anti
      N. caninum KBA-2 immunoglobulin G, and reactive proteins were visualized and
      compared between the two isolates. Most spots on 2-DE profiles and antigenic
      spots on 2-DE immunoblot profiles were located at similar locations in terms of
      isoelectric point and molecular weight. Proteins common to both isolates included
      the following: heat shock protein 70, subtilisin-like serine protease, nucleoside
      triphosphatase, heat shock protein 60, pyruvate kinase, tubulin alpha, tubulin
      beta, enolase, putative protein disulfide isomerase, actin, fructase-1,6
      bisphosphatase, putative ribosomal protein S2, microneme protein Nc-P38, lactate
      dihydrogenase, fructose-1,6-bisphosphatase aldolase, serine threonine phosphatase
      2C, 14-3-3 protein homologue, N. caninum dense granule-1 and NcGRA2. As a
      consequence, even though N. caninum KBA-2 and VMDL-1 isolates were isolated from
      geographically distinct locations there were significant homology in the proteome
      and antigenic proteome profiles. In addition, proteomic approach was verified as
      a useful tool for understanding of host immune response against different
      isolates of protozoa.

PMID- 16098672
TI  - Possible involvement of the spinal nitric oxide/cGMP pathway in vincristine
      induced painful neuropathy in mice.
AB  - The mechanisms that underlie the development of vincristine-induced painful
      neuropathy are poorly understood. The nitric oxide (NO)-cGMP pathway has been
      reported to be involved in the spinal transmission of nociceptive information. In
      the present study, we examined whether alterations in spinal nociceptive
      processing via the NO-cGMP pathway contribute to vincristine-induced painful
      neuropathy in mice. Mice were intraperitoneally treated with vincristine at a
      dose of 0.05 mg/kg 1 day after the measurement of pre-drug latency in the tail
      flick test, and then treated with a dose of 0.125 mg/kg twice a week for 6 weeks.
      In vincristine-treated mice, a significant decrease in tail-flick latencies
      developed at 4 weeks after treatment. Pretreatment with L-arginine (30-300 mg/kg,
      s.c.), a substrate of NO synthase (NOS), dose-dependently increased the tail
      flick latencies in vincristine-treated mice. The L-arginine-induced increase in
      tail-flick latencies in vincristine-treated mice was completely reversed by i.t.
      pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 3-30 nmol), a NOS
      inhibitor. Furthermore, i.t. pretreatment with 8-bromoguanosine 3', 5'-cyclic
      monophosphate (8-Br-cGMP, 0.3-3.0 nmol), a membrane-permeable cGMP analog, dose
      dependently increased the tail-flick latencies in vincristine-treated mice. The
      contents of NO metabolites, cGMP and protein levels of neuronal NOS in the spinal
      cord in vincristine-treated mice were significantly reduced compared to those in
      vehicle-treated naive mice. These results indicate that dysfunction of the L
      arginine/NO/cGMP cascade in the spinal cord may trigger vincristine-induced
      thermal hyperalgesia in mice.

PMID- 16098675
TI  - Neospora caninum seropositivity and association with abortions in dairy cows in
      Mexico.
AB  - The seroprevalence of Neospora caninum infection was estimated from a sample of
      813 cattle from 20 dairy herds in five regions in Mexico. The true prevalence of
      infection was estimated to be 42% (95% CI: 39, 46). Seropositivity was associated
      with abortion (odds ratio (OR)=2.0) and was higher among cows raised on-farm
      (41%), than among replacement cattle purchased outside the farm (28%). The ORs
      relating abortion to seropositivity in individual herds ranged from 1.3 to 10.
      Overall, 26% of the abortions were attributed to N. caninum.

PMID- 16098676
TI  - Influence of dietary protein supply on resistance to experimental infections with
      Haemonchus contortus in Ile de France and Santa Ines lambs.
AB  - The effect of Haemonchus contortus infection in sheep fed with a moderate and
      high protein content diet was evaluated in two breeds of sheep. Forty-eight Ile
      de France and Santa Ines lambs were maintained indoors since birth, in worm-free
      conditions. The lambs were allocated after weaning in four groups of six animals
      per breed, which were either infected or remain uninfected and given access to
      either a moderately or highly metabolizable protein diet. The moderately and
      highly metabolizable protein diets were calculated to supply 75 and 129 g
      metabolizable protein per kg of dry matter (MP/kg DM), respectively. The
      infection consisted of a trickle infection with 300 infective larvae, three times
      a week, for 12 weeks. Significant differences were observed for mast cell,
      globule leukocyte and eosinophil counts in the abomasal mucosa of the infected
      groups compared to the control of both breeds (P<0.05), regardless of the diet
      supplied. Significantly higher IgA anti-L5 antibody was detected in the infected
      Santa Ines groups than in the infected Ile de France groups (P<0.05). Increased
      metabolizable protein supply resulted in larger body weight gain and higher
      packed cell volumes for both breeds (P<0.05). Both breeds showed an increased
      ability to withstand the pathophysiological effects of H. contortus infection
      when given access to the highly metabolizable protein diet. However, increased
      metabolizable protein supply resulted in reduced worm burdens in Santa Ines lambs
      but not in the Ile de France lambs (P<0.05). The present results show that the
      increase in protein content in growing lamb diets may benefit resistance and
      resilience to gastrointestinal parasites but that these benefits may vary among
      breeds.

PMID- 16098677
TI  - Differential in vitro and in vivo glycosylation of human erythropoietin expressed
      in adenovirally transduced mouse mammary epithelial cells.
AB  - The expression of human erythropoietin in the mammary gland is an attractive
      approach to diminish its current production cost. Previous attempts to produce
      erythropoietin in the milk of transgenic animals resulted in very low expression
      levels and in a detrimental effect in the health of the founder animals. Here, we
      show that the direct transduction of the mouse mammary gland with an adenoviral
      vector carrying the cDNA of erythropoietin promotes its expression in milk at a
      level as high as 3.5 mg/ml. The recombinant erythropoietin derived from mouse
      milk showed a different migration and distribution after SDS-PAGE electrophoresis
      as well as a low in vivo hematopoietic activity. Enzymatic deglycosylation showed
      that these molecular weight disparities are in part due to differential
      glycosylation compared to with its counterpart produced in CHO and HC11 cell
      lines. The difference between in vivo and in vitro glycosylation of human
      erythropoietin expressed in adenovirally transduced mammary epithelial cells
      suggests that key enzymes in the glycosylation pathway may be insufficient during
      lactation. Thus, the direct transduction of the mammary epithelium seems to be a
      powerful tool to express toxic proteins in milk at levels high enough for their
      physical, chemical and biological characterization before undertaking the
      generation of a transgenic mammal.

PMID- 16098678
TI  - Control of colorectal metastasis formation by K-Ras.
AB  - Mutational activation of the K-Ras proto-oncogene is frequently observed during
      the very early stages of colorectal cancer (CRC) development. The mutant alleles
      are preserved during the progression from pre-malignant lesions to invasive
      carcinomas and distant metastases. Activated K-Ras may therefore not only promote
      tumor initiation, but also tumor progression and metastasis formation. Metastasis
      formation is a very complex and inefficient process: Tumor cells have to
      disseminate from the primary tumor, invade the local stroma to gain access to the
      vasculature (intravasation), survive in the hostile environment of the
      circulation and the distant microvascular beds, gain access to the distant
      parenchyma (extravasation) and survive and grow out in this new environment. In
      this review, we discuss the potential influence of mutant K-Ras on each of these
      phases. Furthermore, we have evaluated the clinical evidence that suggests a role
      for K-Ras in the formation of colorectal metastases.

PMID- 16098679
TI  - What came first, major depression or substance use disorder? Clinical
      characteristics and substance use comparing teens in a treatment cohort.
AB  - This study utilized data on a treatment cohort from a randomized clinical trial
      that recruited adolescents with co-occurring major depression and substance use
      disorder (N=126). The purpose of this study was to compare adolescents for whom
      the onset of depression was first versus those for whom the onset of substance
      use disorder was first or in the same year as depression. Intake clinical
      evaluations were abstracted to yield common stressors that included childhood
      abuse, early loss or death, exposure to violence, and attachment problems.
      Tobacco, alcohol, and cannabis initiation and dependence were compared for the
      depression first and substance use disorder first groups, and within those groups
      by gender. Among the substances studied, only cannabis dependence was
      significantly more prevalent among those with depression first. Comparisons
      suggest some differences in the developmental path toward comorbid depression and
      substance use disorders, but remarkable similarity in measures of dependence and
      severity. Although small samples limited statistical significance, observed
      differences suggest possible avenues for prevention or intervention.

PMID- 16098680
TI  - Patient characteristics and treatment implications of marijuana abuse among
      bipolar alcoholics: results from a double blind, placebo-controlled study.
AB  - OBJECTIVE: Marijuana abuse, primarily a disorder of adolescents and young adults,
      is highly prevalent among patients with severely ill psychiatric population,
      especially those with bipolar disorder. Additional marijuana abuse may impact on
      the clinical presentation of bipolar illness and may potentially act as mediator
      of treatment response in this population. However, the characterization of
      bipolar disorder patients with additional marijuana abuse and the impact of such
      abuse on treatment outcome has been rarely examined. The aim of this study was to
      characterize bipolar alcoholic patients with comorbid marijuana abuse and test
      the impact of marijuana abuse on alcohol and mood outcome of patients with
      bipolar disorder and comorbid alcohol dependence. METHOD: We conducted secondary
      analyses of a randomized, double blind, placebo-controlled trial testing
      valproate in 52 bipolar alcoholics. Subjects had a comprehensive assessment at
      baseline using structured diagnostic assessments, and they were then assessed
      every 2 weeks for 24 weeks. RESULTS: Twenty-five subjects (48%) reported
      marijuana abuse. Those with co-occurring marijuana abuse were younger, had fewer
      years of education, and had significantly higher number of additional psychiatric
      comorbidity. They also had more severe alcohol and other drug use and were
      significantly more likely to present in the manic phase. The mixed model
      indicated that the placebo-treated marijuana abuse group had the worst alcohol
      use outcome. CONCLUSIONS: Marijuana abuse among patients with bipolar disorder
      and alcohol dependence is associated with higher degree of severity of alcohol
      and other drugs of abuse and may negatively impact on alcohol treatment outcome.

PMID- 16098681
TI  - Joint trajectory analysis of treated adolescents' alcohol use and symptoms over 1
      year.
AB  - OBJECTIVE: This study characterized treated adolescents' alcohol use and symptom
      trajectories over 1 year to describe the form of use trajectories and symptom
      trajectories, and the joint probability of membership in alcohol use and symptom
      trajectory groups. METHOD: 109 teens (age 14-18, 66% male, 94% white), recruited
      from addictions treatment, with a lifetime DSM-IV alcohol diagnosis, reported on
      daily alcohol use and symptoms in monthly phone contacts using the Time Line
      Follow-Back method. A group-based modeling method jointly estimated trajectories
      of use and symptoms. RESULTS: Four alcohol use trajectories were identified:
      "Abstinent" (31%), Low (36%), Increasing (28%), and High Use (5%). Three alcohol
      symptom trajectories were identified: Very Low severity (44%), Mild (44%), and
      High severity (12%). The most frequent joint outcome was "Abstinent" and Very Low
      symptom severity (32%). CONCLUSIONS: Symptom severity was moderately related to
      alcohol use pattern over 1 year. Findings have implications for moving beyond
      relapse defined as a return to "any use" to consideration of treatment outcome in
      terms of a broader pattern of alcohol use and problems.

PMID- 16098682
TI  - Optic neuropathies--importance of spatial distribution of mitochondria as well as
      function.
AB  - Optic neuropathies such as Leber's hereditary optic neuropathy, dominant optic
      atrophy and toxic amblyopia are an important cause of irreversible visual
      failure. Although they are associated with a defect of mitochondrial energy
      production, their pathogenesis is poorly understood. A common feature to all
      these disorders is relatively selective degeneration of the papillomacular bundle
      of retinal ganglion cells resulting central or caecocentral visual field defects.
      The striking similarity in the pattern of clinical involvement seen with these
      disparate disorders suggests a common pathway in their aetiology. The existing
      hypothesis that the optic nerve head has higher energy demands than other tissues
      making it uniquely dependent on oxidative phosporylation is not satisfactory.
      First, other ocular tissues such as photoreceptors, which are more dependent on
      oxidative phosporylation are not affected. Second, other mitochondrial disorders,
      which have a greater impact on mitochondrial energy function, do not affect the
      optic nerve. The optic nerve head has certain unique ultra structural features.
      Ganglion cell axons exit the eye through a perforated collagen plate, the lamina
      cribrosa. There is a sharp discontinuity in the density of mitochondria at the
      optic nerve head, with a very high concentration in the prelaminar nerve fibre
      layer and low concentration behind the lamina. This has previously been
      attributed to a mechanical hold up of axoplasmic flow, which has itself been
      proposed as a factor in the pathogenesis of a number of optic neuropathies. More
      recent evidence shows that mitochondrial distribution reflects the different
      energy requirements of the unmyelinated prelaminar axons in comparison to the
      myelinated retrolaminar axons. The heterogeous distribution of mitochondria is
      actively maintained to support conduction through the optic nerve head. We
      propose that factors that disrupt the heterogeneous distribution of mitochondria
      can result in ganglion cell death. Evidence for this comes from studies of
      cultured cells with the dominant optic atrophy mutation in which mitochondrial
      distribution is altered and from some forms of hereditary spastic paraparesis
      which are associated with optic atrophy. The responsible mutations do not affect
      ATP production until late in the disease but do affect mitochondrial arrangement,
      again showing that mitochondrial distribution as well as energy production by
      individual mitochondria may be important in the pathogenesis of ganglion cell
      death. Greater understanding of the factors localising mitochondria within the
      ganglion cell axon in particular the interaction with cytoskeleton is required to
      formulate new treatments. Boosting energy production alone may not be an
      effective treatment.

PMID- 16098683
TI  - Effects of 5-HT1A and 5-HT2A receptor stimulation on temporal differentiation
      performance in the fixed-interval peak procedure.
AB  - We examined the effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) and 5-HT(2A/2C) receptor agonist 2,5-dimethoxy-4
      iodoamphetamine (DOI) on performance on the fixed-interval peak procedure, and
      the sensitivity of these effects to 5-HT1A and 5-HT2A receptor antagonists (N-[2
      (4-[2-methoxyphenyl]-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide
      [WAY-100635] and ketanserin). Rats were trained to press a lever for food
      reinforcement in 50 min sessions consisting of 32 trials in which the lever was
      continuously available, separated by 10 s inter-trial intervals. In 16 trials,
      reinforcement was delivered following the first response after 30 s had elapsed
      since trial onset (fixed-interval 30 s). In 16 randomly interposed (peak/probe)
      trials, reinforcement was omitted, and the lever remained in the operant chamber
      for 120 s. Response rate in probe trials was plotted against time from trial
      onset. Time to peak response rate (t(peak)) and the Weber fraction were derived
      from modified Gaussian curves fitted to each rat's data. 8-OH-DPAT (0.05 mg kg(
      1)) reduced t(peak) and increased the Weber fraction; the effect on t(peak) was
      antagonized by WAY-100635 (0.1 mg kg(-1)). DOI (0.25 mg kg(-1)) also reduced
      t(peak) and increased the Weber fraction; the reduction of t(peak) was
      antagonized by ketanserin (2 mg kg(-1)). Stimulation of 5-HT1A and 5-HT2A
      receptors alters temporal differentiation in qualitatively similar ways.

PMID- 16098684
TI  - Urinary corticosterone measures: effects of strain and social rank in BKW and CD
      1 mice.
AB  - We used urinary assays as a non-invasive method to examine corticosterone levels
      in two outbred strains of male laboratory mice (BKW and CD-1). Measures were
      taken before and after 2 weeks of pair housing, to examine the effects of social
      stress. We found that CD-1 mice had significantly higher corticosterone levels
      compared to BKW mice both before and after pairing. Behavioural measures provided
      evidence that, when paired, both strains of mice polarised into dominants and
      subordinates, with a higher overall incidence of aggressive acts in the BKW mice.
      Some pairings had to be separated to prevent injuries so the pairing procedure
      introduced a selection for non-aggressive socially tolerant mice. Social status
      was nevertheless found to be associated with pre-existing differences in urinary
      corticosterone in the CD-1 strain: mice that later became dominant had overall
      lower levels of urinary corticosterone compared to subordinates. In conclusion,
      urinary corticosterone levels indicated clear differences in physiology, likely
      to be related to the adrenal stress response, dependent on both strain and social
      status. Thus, this non-invasive measure could help to predict the welfare
      outcomes of social housing and how these may depend on dominance status, rather
      than overall levels of aggression, in different strains of mice.

PMID- 16098685
TI  - Mating activity of yellow and sepia Drosophila willistoni mutants.
AB  - By analyzing the mating activity of newly isolated yellow and sepia mutants of
      Drosophila willistoni no difference in behavior between sepia and wild-type flies
      were observed, whereas yellow males were less successful than wild-type males
      when competing for females. These results are in agreement with those reported
      for other Drosophila species. D. willistoni was different in the 'females
      competing' crosses because wild-type males mated more frequently with wild-type
      females whereas yellow males mated successfully with both phenotypes. These
      results indicate the complexity of the courtship behavior in D. willistoni and
      provide data for comparative and evolutionary research into the genus.

PMID- 16098686
TI  - Transcriptional analysis of the cyclopropane fatty acid synthase gene of
      Lactococcus lactis MG1363 at low pH.
AB  - Cyclopropane fatty acid synthase (cfa) catalyses the transfer of a methyl group
      from S-adenosylmethionine (SAM) to unsaturated fatty acids. Northern blot
      experiments demonstrated that the Lactococcus lactis MG1363 cfa gene is mainly
      expressed as a bicistronic transcript together with metK, the gene encoding SAM
      synthetase, and is highly induced by acidity. The cfa promoter was characterized
      by 5'-RACE PCR, and fused to beta-galactosidase by cloning into the pAK80
      plasmid. This transcriptional fusion was highly induced by acidity (23-fold at pH
      5) as well as during entry into the stationary phase (8-fold) in L. lactis.
      Interestingly, the cfa promoter expression is repressed in a L. lactis relA*
      mutant which accumulates (p)ppGpp, whereas its induction by acidity appeared
      independent of (p)ppGpp in L. lactis and in Escherichia coli.

PMID- 16098687
TI  - Secreted autotransporter toxin produced by a diffusely adhering Escherichia coli
      strain causes intestinal damage in animal model assays.
AB  - Bacterial diarrheal diseases remain a major cause of morbidity and mortality in
      developing countries. Diffusely adhering Escherichia coli (DAEC) is a newly
      proposed category of diarrheagenic E. coli based on epidemiological studies. Sat,
      a new virulence factor of some uropathogeic Escherichia coli, was described with
      a vacuolating cytotoxic action in bladder and kidney tissues. In the present
      study, we analyzed the Sat effects, produced by a DAEC strain in rabbit ileal
      intestinal tissue and cultured epithelial cells. We observed enterotoxic activity
      in rabbit ileum tissues by Ussing chamber assays, a pronounced fluid accumulation
      in rabbit ileum loops with villous necrosis observed in the histopathologic
      examination, and morphological changes in monolayer cultures of Y1 adrenal cells.
      Our results suggest that DAEC strains may be involved in diarrhea.

PMID- 16098688
TI  - Pseudomonas aeruginosa rhamnolipids disperse Bordetella bronchiseptica biofilms.
AB  - We have previously reported that the respiratory pathogen Bordetella
      bronchiseptica can form biofilms in vitro. In this report, we demonstrate the
      disruption of B. bronchiseptica biofilms by rhamnolipids secreted from
      Pseudomonas aeruginosa. This suggests that biosurfactants such as rhamnolipids
      may be utilized as antimicrobial agents for removing Bordetella biofilms.

PMID- 16098689
TI  - Influence of nutrition on the production and physiology of sectors produced by
      the insect pathogenic fungus Metarhizium anisopliae.
AB  - Metarhizium anisopliae strains V245 and V275 differed in their stability when
      grown on different nutrient media. V275 produced fewer sectors than V245
      irrespective of the cultural conditions. Both strains produced more sectors on
      nutrient rich media. At least four distinct types of sectors were produced in
      vitro. Most sectors were sterile or sporulated poorly and produced significantly
      lower quantities of virulence determining enzymes like Pr1. Real-time PCR
      confirmed differential expression of the pathogenicity-related genes pr1 A, ste
      1, try 1, and chy 1 encoding for the subtilisin Pr1A, esterase, trypsin and
      chymotrypsin, respectively. API-ZYM revealed that the enzyme profiles of sectors
      differed from those of the parent cultures and also from other sectors. Sectors
      of M. anisopliae also produced less destruxins than the parent cultures
      independent of the strain.

PMID- 16098690
TI  - Listeria monocytogenes ferritin protects against multiple stresses and is
      required for virulence.
AB  - In this study, the role of Listeria monocytogenes ferritin was investigated. The
      fri gene encoding the ferritin was deleted and the phenotype of the mutant was
      analyzed demonstrating that ferritin is necessary for optimal growth in minimal
      medium in both presence and absence of iron, as well as after cold- and heat
      shock. We also showed that ferritin provides protection against reactive oxygen
      species and is essential for full virulence of L. monocytogenes. A comparative
      proteomic analysis revealed an effect of the fri deletion on the levels of
      listeriolysin O and several stress proteins. Together, our study demonstrates
      that fri has multiple roles that contribute to Listeria virulence.

PMID- 16098691
TI  - Rapid detection and identification of the metabolically diverse genus Gordonia by
      16S rRNA-gene-targeted genus-specific primers.
AB  - The importance of the emerging genus Gordonia in industrial and environmental
      biotechnology is evidenced by the recent increase in associated publications and
      patents. But, investigations into potentially valuable Gordonia members are
      restricted by the limitations of current isolation and detection techniques. This
      motivated us to design a genus-specific oligonucleotide primer pair which could
      assist in rapid detection of species of the genus Gordonia by means of PCR
      specific amplification. The Gordonia-specific 16S rDNA fragment (829 bp) was
      successfully amplified for all the reference Gordonia species with the designed
      primer pair G268F/G1096R. No amplification was noted for closely related species
      from other genera. The genus specificity was validated with 47 strains including
      wild-type isolates. Interestingly, two strains assigned earlier as Gordonia
      nitida (DSM 777) and Gordonia rubripertinctus (ATCC 21930) failed to produce a
      Gordonia-specific fragment with this primer pair. Further analysis of these two
      isolates based on 16S rDNA sequencing and phylogenetic analysis classified them
      to the genus Rhodococcus. Preliminary screening of soil samples with the Gordonia
      specific primers was successful in terms of the rapid detection of nine Gordonia
      wild-type isolates.

PMID- 16098692
TI  - Probability of porcine reproductive and respiratory syndrome (PRRS) virus
      infection as a function of exposure route and dose.
AB  - At the most elemental level, the design of effective strategies to control and/or
      eliminate porcine reproductive and respiratory syndrome (PRRS) virus depend on an
      accurate and comprehensive understanding of virus transmission. As a general
      rule, transmission is highly dependent on the route of exposure and the dose of
      virus. The objective of this study was to derive PRRS virus isolate VR-2332 dose
      response curves for oral and intranasal routes of exposure, i.e., determine the
      probability that a specific virus dose would result in infection. Individually
      housed pigs approximately 21 days of age were exposed to specific doses of PRRS
      virus isolate VR-2332 by either oral or intranasal routes. Positive controls were
      intramuscularly inoculated with 10(2.2) 50% tissue culture infective dose
      (TCID50) of PRRS virus and negative controls were orally administered 100ml of
      diluent with no virus. Pigs were monitored for evidence of infection for 21 days
      following exposure, i.e., serum samples were collected on days 0, 7, 14, 21, and
      tested for virus and PRRS virus-specific antibodies. Dose-response curves and 95%
      confidence intervals for oral and intranasal routes of exposure were derived
      using logistic models (logit and probit). The infectious dose50 (ID50) for oral
      exposure was estimated to be 10(5.3) TCID50 (95% CI, 10(4.6) and 10(5.9)); the
      ID50 for intranasal exposure was estimated to be 10(4.0) TCID50 (95% CI, 10(3.0)
      and 10(5.0)). Given these estimates, it is worth noting that intramuscular
      exposure of animals to 10(2.2) TCID50 (positive controls) resulted in infection
      in all animals. Thus pigs were the most susceptible to infection via parenteral
      exposure.

PMID- 16098693
TI  - Increased cytochrome P4501B1 gene expression in peripheral leukocytes of
      municipal waste incinerator workers.
AB  - Incinerator workers are exposed to polycyclic aromatic hydrocarbons (PAHs) and
      dioxins in workplace. Previous studies indicated that aryl hydrocarbon receptor
      activation, following by increased cytochrome P4501A1 (CYP1A1) and 1B1 (CYP1B1)
      activity and expressions, was required for PAHs and dioxin induced toxicities.
      This study investigated whether municipal waste incinerator workers with frequent
      exposure to PAHs/dioxins in fly/bottom ash had increased CYP1A1 and CYP1B1
      expressions in peripheral leukocytes and assessed whether CYP1B1*3 polymorphism
      modified the association between PAHs/dioxins exposure and CYP1B1 expressions.
      Based on job contents and time-activity profiles, 112 workers were classified
      into high exposure, medium exposure and control groups. CYP1A1 and CYP1B1 gene
      expressions in workers' leukocytes were determined with the real-time reverse
      transcriptase polymerase chain reaction method. After taking into account age,
      gender and smoking in the multiple regression analyses, CYP1B1, but not CYP1A1,
      levels were significantly higher in the high and medium exposure groups than in
      the control group, and there was a statistically significant interaction between
      exposure group and CYP1B1 genotype. These results suggested that CYP1B1 gene
      expression could be a potential biomarker of biologically effective dose for
      occupational exposure to PAHs/dioxins and CYP1B1*3 polymorphism modified effects
      of occupational exposures on CYP1B1 expression.

PMID- 16098694
TI  - Sulphated glycosaminoglycans (S-GAGs) and syndecans in the bovine oviduct.
AB  - In vivo, bull sperm capacitation seems to occur mainly in the oviduct.
      Capacitation of bull spermatozoa can be triggered in vitro by exposure to
      heparin, a heavily sulphated glycosaminoglycan (S-GAG). We determined the
      concentration of S-GAGs in oviductal fluid from dairy heifers, collected over the
      course of several oestrous cycles via surgically implanted intraluminal
      catheters. We also investigated the presence of syndecans, i.e. heparan sulphate
      proteoglycans, in the bovine oviductal epithelium of Swedish dairy cattle during
      standing oestrus and the luteal phase of the oestrous cycle, using
      immunohistochemistry for three different polyclonal antibodies raised against
      human syndecan-2 and rat syndecan-1 and syndecan-2, respectively. The
      concentration of S-GAGs in oviductal fluid obtained from the ampullar segment of
      the oviduct was significantly higher (P=0.0026) than it was in fluid from the
      isthmic segment during the functional period, i.e. from prooestrus to metaoestrus
      (73.5+/-10.49 mg/L in ampullar ODF, compared to 43.2+/-10.74 mg/L in isthmic
      ODF); least square mean (L.S.M.)+/-standard error of the mean (S.E.M.). There was
      also a significantly higher concentration of S-GAGs in the fluid from the oviduct
      ipsilateral to the ovulation side 73.5+/-10.54 mg/L on the ovulation side,
      compared to 43.1+/-10.71 mg/L in the oviduct on the contralateral side (L.S.M.+/
      S.E.M., P=0.0026) during this period. Both syndecan-1 and syndecan-2 were present
      in the epithelial cells lining all studied segments of the bovine oviduct, i.e.
      the UTJ, isthmus and ampulla, during both standing oestrus and dioestrus. The
      syndecans and S-GAGs found may influence the gametes, while they reside in the
      oviduct; the amounts of S-GAGs found in the bovine oviduct seem sufficient to act
      as capacitating factors in vivo.

PMID- 16098695
TI  - Adsorption kinetics of plasma proteins on solid lipid nanoparticles for drug
      targeting.
AB  - The interactions of intravenously injected carriers with plasma proteins are the
      determining factor for the in vivo fate of the particles. In this study the
      adsorption kinetics on solid lipid nanoparticles (SLN) were investigated and
      compared to the adsorption kinetics on previously analyzed polymeric model
      particles and O/W-emulsions. The adsorbed proteins were determined using two
      dimensional polyacrylamide gel electrophoresis (2-DE). Employing diluted human
      plasma, a transient adsorption of fibrinogen was observed on the surface of SLN
      stabilized with the surfactant Tego Care 450, which in plasma of higher
      concentrations was displaced by apolipoproteins. This was in agreement with the
      "Vroman-effect" previously determined on solid surfaces. It says that in the
      early stages of adsorption, more plentiful proteins with low affinity are
      displaced by less plentiful with higher affinity to the surface. Over a period of
      time (0.5 min to 4 h) more interesting for the organ distribution of long
      circulating carriers, no relevant changes in the composition of the adsorption
      patterns of SLN, surface-modified with poloxamine 908 and poloxamer 407,
      respectively, were detected. This is in contrast to the chemically similar
      surface-modified polymeric particles but well in agreement with the surface
      modified O/W-emulsions. As there is no competitive displacement of
      apolipoproteins on these modified SLN, the stable adsorption patterns may be
      better exploited for drug targeting than particles with an adsorption pattern
      being very dependent on contact time with plasma.

PMID- 16098696
TI  - Anti-inflammatory effects by transdermal application of triamcinolone acetonide
      gel using phonophoresis in rats.
AB  - The present study was carried out to determine the feasibility of using gel
      formulations for the transdermal delivery of triamcinolone acetonide (TA), which
      is one of the synthetic glucocorticoids, in conjunction with phonophoresis, and
      to develop the carbopol gels of TA. For this purpose, the anti-inflammatory
      effects of the gel containing TA after the adoption of ultrasound were evaluated
      by investigating the in vivo change in the serum creatine phosphokinase (CPK) and
      histological findings. Following a muscle injury, the serum CPK activity
      decreased significantly in the TA gel group with phonophoresis, comparing with
      that in the control group and the commercial gel group given ultrasound. In the
      gross finding, after a muscle injury, the TA gel group with phonophoresis showed
      rapid moderation of the injury compared with the three other groups. The
      histological findings showed that the inflammation was relieved within 72 h after
      the injury from the TA gel group with phonophoresis. These effects were
      considerably higher in the phonophoresis group than in the other three groups.
      Overall, a TA gel using phonophoresis might be used as a new transdermal delivery
      technique providing enhanced anti-inflammatory effects.

PMID- 16098697
TI  - Cortical responses to promontorial stimulation in postlingual deafness.
AB  - Electrical stimulation with a transtympanic electrode on the promontory of the
      middle ear allows the tasks of gap detection and temporal difference limen (TDL)
      to be carried out by both normally hearing and deaf subjects. Previous
      neuroimaging of normally hearing subjects revealed a region in the right
      posterior temporal lobe that is crucial to duration discrimination. The present
      study tested the hypothesis that postlingually deaf subjects recruit this area
      when they make subtle temporal discriminations. Fourteen postlingually deaf adult
      cochlear implant candidates were stimulated in the ear chosen for implantation.
      Altered cerebral activity was recorded with positron emission tomography as
      incremental 15-O-labelled water uptake. On stimulation with tone bursts, we found
      bilateral activity close to the primary auditory cortex in all subjects. However,
      subjects performing well on the TDL task demonstrated right-lateralized fronto
      temporal and left-lateralized temporal activity in the respective TDL and gap
      detection tasks, while subjects who failed to detect duration differences of less
      than 200 ms in the TDL discrimination task only had frontal and occipital rather
      than temporal lobe activation. We conclude that the ability to involve the right
      posterior temporal region is important to duration discrimination. This ability
      can be evaluated pre-operatively.

PMID- 16098698
TI  - A Swedish collection of medicinal plants from Cameroon.
AB  - A collection of 32 botanically identified medicinal plants from the slopes of Mt.
      Cameroon made by two Swedish settlers in the beginning of the last century is
      described and the literature is followed up. The drug names were found to be
      unaltered during the century passed.

PMID- 16098699
TI  - Discovery and identification of new D13S317 primer binding site mutations.
AB  - During the course of conventional testing of CODIS standards at the Alabama
      Department of Forensic Sciences, a sample with a heterozygous null genotype at
      D13S317 was discovered using the PowerPlex 1.1 kit (Promega, Madison, WI). The
      loss of both alleles was confirmed when the sample was amplified using PowerPlex
      1.2 primers and resulted in a 9, 10 genotype at this locus. To determine the
      cause of the silent alleles, the ADFS designed D13S317 primers which encompassed
      the PowerPlex 1.1 D13S317 primer binding sites and sequenced the region. Both
      alleles showed the presence of two substitutions (T-->A and G-->T) at positions 1
      and 5 (5'-->3') of the reverse primer (positions 196 and 200 of the sequence in
      GenBank accession number ). Since the mutations were identical on both alleles,
      they may be assumed to be of ancestral origin.

PMID- 16098700
TI  - Effects of liquid chromatography mobile phases and buffer salts on phosphorus
      inductively coupled plasma atomic emission and mass spectrometries utilizing
      ultrasonic nebulization and membrane desolvation.
AB  - Atomic spectrometry, specifically inductively coupled plasma atomic emission
      spectrometry (ICP-AES) and mass spectrometry (ICP-MS) show promise for heteroatom
      based detection of pharmaceutical compounds. The combination of ultrasonic
      nebulization (USN) with membrane desolvation (MD) greatly enhances detection
      limits with these approaches. Because pharmaceutical analyses often incorporate
      liquid chromatography, the study herein was performed to examine the effects of
      solvent composition on the analytical behaviors of these approaches. The target
      analyte was phosphorus, introduced as phosphomycin. AES response was examined at
      the 253.7 nm atom line and mass 31 ions were monitored for the MS experiments.
      With pure aqueous solutions, detection limits of 5 ppb (0.5 ng in 0.1 mL
      injection volumes) were obtained with ICP-MS. The ICP-AES detection limit was 150
      ppb. Solvent compositions were varied from 0 to 80% organic (acetonitrile and
      methanol) with nine buffers at concentrations typically used in liquid
      chromatography. In general, solvents and buffers had statistically significant,
      albeit small, effects on ICP-AES sensitivities. A few exceptions occurred in
      cases where typical liquid chromatography buffer concentrations produced higher
      mass loadings on the plasma. Indications are that isocratic separations can be
      reliably performed. Within reasonable accuracy tolerances, it appears that
      gradient chromatography can be performed without the need for signal response
      normalization. Organic solvent and buffer effects were more significant with ICP
      MS. Sensitivities varied significantly with different buffers and organic solvent
      content. In these cases, gradient chromatography will require careful analytical
      calibration as solvent and buffer content is varied. However, for most buffer and
      solvent combinations, signal and detection limits are only moderately affected.
      Isocratic separations and detection are feasible.

PMID- 16098701
TI  - Challenges and opportunities for enhancing biotechnology and technology transfer
      in developing countries.
AB  - Biotechnological innovation is gaining increased recognition as an important tool
      for improving global health. The challenge, however, lies in defining the role of
      technology transfer to develop therapies for diseases prevalent in developing
      countries. During the past decade, a large disparity emerged between the
      developed and developing world in accessing affordable medicines because of the
      pharmaceutical industry's focus on health areas bearing greatest profits.
      Discussed herein are several mechanisms that provide partial solutions to this
      challenge. The Office of Technology Transfer of the US National Institutes of
      Health has increased its technology licensing pertaining to neglected diseases to
      partners in developing regions. Establishing partnerships through the transfer of
      technologies and assisting indigenous institutions build R and D capacity may
      positively impact policies on protection of intellectual property rights and
      increase multinational company investments in lesser-developed countries. This
      will most probably result in the development of more accessible therapies for
      those in need.

PMID- 16098703
TI  - A course of instruction for women with irritable bowel syndrome.
AB  - OBJECTIVE: The aim of this study was to determine the effects a course of
      instruction about irritable bowel syndrome (IBS) might have on symptoms,
      psychological well-being, and medical care requirements in these patients.
      METHODS: Twenty-nine women with IBS participated in a programme of instruction on
      medical care, physical activity, stress-management, diet and health insurance.
      The women completed the Gastrointestinal Symptom Rating Scale and the
      Psychological General Well-Being Index and provided information about their
      requirements of medical care before and after the course. RESULTS: Twenty-three
      of the women included, completed the questionnaires at 12 months after the
      course. When comparing these values to those at baseline, there were improvements
      in abdominal pain (p < 0.037) and vitality (p < 0.045) as well as a reduction in
      the number of visits to physicians (p < 0.037) and dieticians (p < 0.042).
      CONCLUSION: Information related to the disease, might help women with IBS to
      perceive less pain and more vitality and thereby experience a higher quality of
      life. PRACTICE IMPLICATIONS: A course of instruction for patients with IBS may be
      of benefit for the patients, and could be a part of a multicomponent approach in
      the treatment of this patient group.

PMID- 16098704
TI  - Six-month effects of the Groningen active living model (GALM) on physical
      activity, health and fitness outcomes in sedentary and underactive older adults
      aged 55-65.
AB  - OBJECTIVE: To determine the effects on energy expenditure, health and fitness
      outcomes in sedentary older adults aged 55-65 after 6-month participation in the
      GALM program. METHODS: In three Dutch communities, subjects from matched
      neighbourhoods were assigned to an intervention (n = 79) or a waiting-list
      control group (n = 102). The GALM program consisted of fifteen 60 min sessions
      once a week emphasising moderate-intensity recreational sports activities.
      RESULTS: The intervention group showed significant increases in energy
      expenditure for recreational sports activities, other leisure-time physical
      activity, health indicators, and perceived and performance-based fitness.
      Contrary to our expectations, the same increases were found for the control
      group. Consequently, only significant between-group differences, favouring the
      intervention group, were obtained for sleep, diastolic blood pressure, perceived
      fitness score and grip strength. CONCLUSION: The increases in energy expenditure
      for physical activity from the GALM program, especially for the more intensive
      recreational sports activities, look promising and are in line with the expected
      amounts necessary to improve health. Further research is needed to evaluate long
      term effects of participation in the GALM program. PRACTICE IMPLICATIONS: These
      results underline that GALM can be considered successful in stimulating leisure
      time physical activity and improving health and fitness in older adults.

PMID- 16098705
TI  - Patients' experiences related to anti-viral treatment for hepatitis C.
AB  - OBJECTIVE: To conduct a qualitative study to elicit patients' descriptions of
      their own experiences with treatment for hepatitis C (HCV). METHODS: Focus groups
      were conducted until thematic saturation was reached. RESULTS: A total of 40
      patients (80% male) participated in eight focus groups. The themes that emerged
      most frequently during the focus groups centered on adverse effects and quality
      of care. The discussions highlighted discrepancies between patients' anticipated
      effects of drug toxicity versus their actual experiences, gaps in communication
      between physicians, and the lack of social support as important shortcomings in
      the healthcare of HCV patients. CONCLUSIONS: The issues raised by the
      participants in this study highlight several important areas that may lead to
      improved care for patients with HCV. PRACTICE IMPLICATIONS: This study suggests
      that care for patients with HCV might be improved by using patient testimonials
      to improve accuracy of expectations, having both the primary care physician and
      liver specialist devise a plan to treat symptoms arising during the course of
      therapy, and ensuring that patients have the option of participating in a support
      group.

PMID- 16098706
TI  - Evidence-based patient information about treatment of multiple sclerosis--a phase
      one study on comprehension and emotional responses.
AB  - OBJECTIVE: This study analysis the comprehension and emotional responses of
      people suffering from multiple sclerosis when provided with an evidence-based
      information module. It is a core module of a comprehensive decision aid about
      immunotherapy. The core module is designed to enable patients to process
      scientific uncertainty without adverse effects. It considers existing standards
      for risk communication and presentation of data. METHODS: Using a mailing
      approach we investigated 169 patients with differing courses of disease in a
      before-after design. Items addressed the competence in processing relative and
      absolute risk information and patients' emotional response to the tool,
      comprising grade of familiarity with the information, understanding, relevance,
      emotional arousal, and certainty. RESULTS: Overall, numeracy improved (p <
      0.001), although 99 of 169 patients did not complete the numeracy task correctly.
      Understanding depended on the relevance related to the course of disease. A
      moderate level of uncertainty was induced. No adverse emotional responses could
      be shown, neither in those who did comprehend the information, nor in those who
      did not develop numeracy skills. CONCLUSION: In conclusion, the tool supports
      people suffering from multiple sclerosis to process evidence-based medical
      information and scientific uncertainty without burdening them emotionally.
      PRACTICE IMPLICATIONS: This study is an example for the documentation of an
      important step in the development process of a complex intervention.

PMID- 16098707
TI  - Perceived barriers to and benefits of attending a stop smoking course during
      pregnancy.
AB  - OBJECTIVE: During pregnancy, the uptake of smoking cessation courses is very low.
      We assessed perceived barriers to and benefits of attending a cessation course
      during pregnancy. METHODS: A decisional-balance questionnaire was devised,
      including 10 statements reflecting benefits of attending a cessation course and
      10 statements of barriers to attendance. The questionnaire was delivered via the
      Internet and targeted pregnant smokers/recent ex-smokers. Participants completed
      the questionnaire on a single occasion, indicating their agreement with each
      statement. RESULTS: Among 443 respondents, the most frequently endorsed barriers
      were 'Being afraid of disappointing myself if I failed' (54%) and not tending to
      seek help for this sort of thing (41%). The most frequently endorsed benefits
      were advice about cigarette cravings (74%) and praise and encouragement with
      quitting (71%). A greater interest in receiving help with quitting from a
      counselor was significantly associated with: being older, lower income,
      husband/partner advising cessation and less confidence in quitting. CONCLUSION:
      Pregnant smokers perceive many benefits of smoking cessation courses. However,
      these women also perceive many barriers to attendance and studies are needed to
      evaluate interventions for overcoming such barriers. PRACTICE IMPLICATIONS:
      Smoking cessation services need to address the perceived barriers to attending
      stop smoking courses during pregnancy, to publicise the benefits of these courses
      and to target women who feel that they cannot quit without this type of support.

PMID- 16098708
TI  - Analysis of stroke patients' and carers' reading ability and the content and
      design of written materials: recommendations for improving written stroke
      information.
AB  - OBJECTIVE: This study (a) evaluated the reading ability of patients following
      stroke and their carers and the reading level and content and design
      characteristics of the written information provided to them, (b) explored the
      influence of sociodemographic and clinical characteristics on patients' reading
      ability, and (c) described an education package that provides well-designed
      information tailored to patients' and carers' informational needs. METHODS: Fifty
      seven patients and 12 carers were interviewed about their informational needs in
      an acute stroke unit. Their reading ability was assessed using the Rapid Estimate
      of Adult Literacy in Medicine (REALM). The written information provided to them
      in the acute stroke unit was analysed using the SMOG readability formula and the
      Suitability Assessment of Materials (SAM). RESULTS: Thirteen (22.8%) patients and
      5 (41.7%) carers had received written stroke information. The mean reading level
      of materials analysed was 11th grade while patients read at a mean of 7-8th
      grade. Most materials (89%) scored as only adequate in content and design.
      Patients with combined aphasia read significantly lower (4-6th grade) than other
      patients (p=0.001). CONCLUSION: Only a small proportion of patients and carers
      received written materials about stroke and the readability level and content and
      design characteristics of most materials required improvement. PRACTICE
      IMPLICATIONS: When developing and distributing written materials about stroke,
      health professionals should consider the reading ability and informational needs
      of the recipients, and the reading level and content and design characteristics
      of the written materials. A computer system can be used to generate written
      materials tailored to the informational needs and literacy skills of patients and
      carers.

PMID- 16098709
TI  - TNF-based isolated limb perfusion in unresectable extremity desmoid tumours.
AB  - BACKGROUND: Desmoid tumours are soft tissue sarcomas with local aggressive
      behaviour and a high rate of local recurrence after treatment. Although they do
      not tend to metastasise systemically, the local aggressiveness can lead to
      situations in which limb-preserving surgery cannot be performed without severe
      disability. As isolated limb perfusion (ILP) with TNF and melphalan has proven to
      be extremely effective in the treatment of soft tissue sarcoma, we studied its
      potential in locally advanced extremity desmoid tumours. METHODS: Prospectively
      maintained database in a tertiary referral centre. Between 1991 and 2003, 12 ILP
      procedures were performed in 11 patients for locally advanced desmoid tumours.
      Local surgical therapy with preservation of limb function was impossible in all
      patients due to large or multifocal tumours, multiple recurrences or extensive
      previous treatment. Perfusions were performed with 4-3mg TNF and 10-13 mg/l limb
      volume melphalan form leg and arm perfusions, respectively. RESULTS: Overall
      response rate was 75%: Two complete responses were recorded (17%) and seven
      patients had a partial response (58%). Amputation could be avoided in all cases.
      Local control was obtained after 10/12 ILPs and in the other two patients through
      repeat ILP and systemic chemotherapy, thus leading to an overall local control
      rate of 100%. Local toxicity was mild and systemic toxicity was absent in all
      patients. CONCLUSION: ILP is a very effective treatment option in the
      multimodality treatment of limb desmoid tumours. It should be considered in
      patients with aggressive and disabling disease where resection without important
      functional sacrifice is impossible.

PMID- 16098710
TI  - The 19-kDa antigen of Mycobacterium tuberculosis is a major adhesin that binds
      the mannose receptor of THP-1 monocytic cells and promotes phagocytosis of
      mycobacteria.
AB  - Identification of mycobacterial adhesins is needed to understand better the
      pathogenesis of tuberculosis and to develop new strategies to fight this
      infection. In this work, THP-1 monocytic cells were incubated with Mycobacterium
      tuberculosis culture filtrate proteins labelled with biotin and a dominant 19-kDa
      adhesin was found. This adhesin was characterized as the glycosylated and
      acylated 19-kDa antigen (Rv 3763). These findings were confirmed in assays with
      culture filtrate proteins and cell-wall fractions from a recombinant
      Mycobacterium smegmatis strain that overexpresses the 19-kDa antigen. Further,
      fluorescent microspheres coated with recombinant culture filtrate proteins adhere
      to cells in higher numbers than microspheres coated with native M. smegmatis
      proteins. The binding of the 19-kDa antigen to cells was inhibited with mannose
      receptor competitor sugars, Ca(2+) chelators and with a monoclonal antibody to
      the human mannose receptor. Phagocytosis assays showed high-level binding of
      bacilli to THP-1 cells that was inhibited with alpha-methyl-mannoside, mannan,
      EDTA and mAbs to the mannose receptor and to the 19-kDa M. tuberculosis antigen.
      Immunoprecipitation, cell-surface ELISA and immunostaining confirmed the
      expression of the mannose receptor by THP-1 cells. In conclusion, here we show
      that the macrophage mannose receptor, considered a pathogen pattern recognition
      receptor, may interact with mannose residues of mycobacterial glycoproteins that
      could promote the phagocytosis of mycobacteria.

PMID- 16098711
TI  - An in vivo and in vitro comparison of CYP gene induction in mice using liver
      slices and quantitative RT-PCR.
AB  - The scope of this study was to compare in vitro and in vivo cytochrome P450 (CYP)
      gene induction in mice, using liver slices as an in vitro model. We have chosen
      to study mice to be able to better interpret CYP induction during long-term
      safety studies in this species. Mouse liver slices were incubated with beta
      naphthoflavone (betaNF), phenobarbital (PB) or dexamethasone (DEX) for 24 h. In
      addition, in an in vivo study, mice were treated with the same compounds for
      three days. The mRNA expression of cyp1a1, cyp1a2, cyp2b10 and cyp3a11, which are
      important for drug metabolism and inducible by xenobiotics, were investigated in
      vivo and in vitro by real-time quantitative reverse transcription-polymerase
      chain reaction (RT-PCR). Both in mouse liver slices and in vivo, betaNF was found
      to be a potent inducer of cyp1a1 and to a lesser extent of cyp1a2. All three
      compounds induced cyp2b10 mRNA levels, while the cyp3a11 mRNA level was induced
      only by DEX. Overall, these data demonstrated a good predictive in vitro-in vivo
      correlation of CYP induction.

PMID- 16098712
TI  - Assessment and integration of publicly available SAGE, cDNA microarray, and
      oligonucleotide microarray expression data for global coexpression analyses.
AB  - Large amounts of gene expression data from several different technologies are
      becoming available to the scientific community. A common practice is to use these
      data to calculate global gene coexpression for validation or integration of other
      "omic" data. To assess the utility of publicly available datasets for this
      purpose we have analyzed Homo sapiens data from 1202 cDNA microarray experiments,
      242 SAGE libraries, and 667 Affymetrix oligonucleotide microarray experiments.
      The three datasets compared demonstrate significant but low levels of global
      concordance (rc<0.11). Assessment against Gene Ontology (GO) revealed that all
      three platforms identify more coexpressed gene pairs with common biological
      processes than expected by chance. As the Pearson correlation for a gene pair
      increased it was more likely to be confirmed by GO. The Affymetrix dataset
      performed best individually with gene pairs of correlation 0.9-1.0 confirmed by
      GO in 74% of cases. However, in all cases, gene pairs confirmed by multiple
      platforms were more likely to be confirmed by GO. We show that combining results
      from different expression platforms increases reliability of coexpression. A
      comparison with other recently published coexpression studies found similar
      results in terms of performance against GO but with each method producing
      distinctly different gene pair lists.

PMID- 16098713
TI  - Rapid detection of codon 460 mutations in the UL97 gene of ganciclovir-resistant
      cytomegalovirus clinical isolates by real-time PCR using molecular beacons.
AB  - A rapid real-time polymerase chain reaction (PCR) assay using molecular beacons
      has been developed for the simultaneous detection of wild-type and mutant strains
      of cytomegaloviruses (CMV) with respect to codon 460 of the UL97 gene has been
      developed. The molecular beacons were designed to complement the wild-type codon
      460 or the mutant sequence arising from a single base-pair difference (point
      mutation). Discrimination between wild-type and mutant templates was demonstrated
      as the beacons did not generate fluorescence with their respective mismatch
      targets but only with those that they were designed to perfectly anneal with.
      Samples that harbor mixed populations of CMV could also be readily recognized.
      Applied to a small number of clinical samples, the retrospective screening by
      this assay are in general concordance with that obtained by PCR-RFLP. Using
      molecular beacons strategy, codon 460 mutation was detected in ten out o the
      total number of 40 samples, whereas the latter method identified nine samples as
      containing the mutation. The discrepant result arose from the genotyping of one
      clinical sample as mixed (containing both wild-type and mutant CMV strains) by
      molecular beacons but as wild-type by PCR-RFLP, suggesting that this real-time
      strategy is possibly more sensitive for mutation analysis.

PMID- 16098714
TI  - alpha(2)-Adrenergic receptors activate MAPK and Akt through a pathway involving
      arachidonic acid metabolism by cytochrome P450-dependent epoxygenase, matrix
      metalloproteinase activation and subtype-specific transactivation of EGFR.
AB  - Previous study carried out on PC12 cells expressing each alpha(2)-adrenergic
      receptor subtype individually (PC12/alpha(2A), /alpha(2B) or /alpha(2C)) have
      shown that epinephrine causes activation of PI3K and phosphorylation of Erk 1/2.
      The signal transduction mechanisms whereby each alpha(2)-AR subtype triggers
      these actions were investigated in the present study. In all three clones,
      epinephrine-induced phosphorylation of MAPK or Akt was abolished by prior
      treatment with ketoconazole, but not with indomethacin or nordihydroguaiaretic
      acid. On the other hand, treatment of the clones with epinephrine caused a rapid
      increase of AA release, which was fully abolished by the PLC inhibitor U73122,
      but was unaffected by the PLA(2) inhibitor quinacrine. The effects of epinephrine
      on MAPK and Akt were mimicked by cell exposure to exogenous AA. Furthermore,
      whereas U73122 abolished the effects of epinephrine, quinacrine only prevented
      the effects of epinephrine, suggesting that AA release through PLC and its
      metabolites are responsible for MAPK and Akt activation by alpha(2)-ARs.
      Treatment with 1,10-phenanthroline, CRM197, or tyrphostin AG1478 suppressed MAPK
      and Akt phosphorylation by epinephrine or AA, in a subtype-specific manner.
      Furthermore, conditioned culture medium from epinephrine-treated PC12/alpha(2)
      induced MAPK and Akt phosphorylation in wild-type PC12. Inhibition of NGFR
      tyrosine phosphorylation had no effect but the src inhibitor PP1 abolished MAPK
      and Akt phosphorylation in all three clones. Our results provide evidence for a
      putative pathway by which alpha(2)-ARs activate MAPK and Akt in PC12 cells,
      involving stimulation of PLC, AA release, AA metabolism by cytochrome P450
      dependent epoxygenase, stimulation of matrix metalloproteinases and subtype
      specific transactivation of EGFR through src activation and heparin-binding EGF
      like growth factor release.

PMID- 16098715
TI  - Signalling pathway in the induction of neurite outgrowth in human mesenchymal
      stem cells.
AB  - Recent in vivo transplantation studies have shown that mesenchymal stem cells
      (MSCs) were able to differentiate into mesoderm-derived cell types as well as
      cells with neuroectodermal characteristics, suggesting that transdifferentiation
      occurs in the mammalian system. We have reported an immortalized line of human
      MSCs (hMSCs), KP-hMSCs, which expresses CD29, CD44, CD90, and CD105, and complies
      with the characteristics shared by mere hMSCs. In a current experiment, we
      further demonstrated that expanded KP-hMSCs exhibited markers of neuroepithelial
      or neural precursor cells, such as Nestin, Musashi-1, Vimentin, NCAM, Pax-6, and
      Sox-9. KP-hMSCs simultaneously expressed proteins of the neuronal, astrocyte, and
      oligodendrocyte lineages during culture expansion; in addition, they initiated
      neurite outgrowth and eradicated protein expressions of astrocyte and
      oligodendrocyte lineages in response to the elevated signaling of the cAMP-PKA
      pathway after serum depletion in a defined neural induction medium. From the
      current results, KP-hMSCs may be used to elucidate molecular signaling on the
      neural differentiation of adult human non-neural tissues. We also presented
      evidence for the possibility that adult MSCs and fetal neuroepithelial or neural
      precursor cells both provide for the continual maintenance and repair of the
      postnatal neural tissues and may derive from the same origin or have one deriving
      from the other.

PMID- 16098716
TI  - Effects of lower third molar extraction on attachment level and alveolar bone
      height of the adjacent second molar.
AB  - Several conflicting findings have been published in previous literature regarding
      the effects of impacted third molar extraction on the periodontal health of the
      adjacent second molar; some authors have shown improvement of periodontal health
      distal to the adjacent second molar, whilst others have demonstrated loss of
      attachment and reduction of alveolar bone height. The purpose of this controlled
      clinical and radiographic study is to evaluate the long-term changes in
      periodontal health and alveolar bone height distal to the adjacent second molar
      following extraction of an impacted third molar. This split-mouth design study
      included 25 patients who underwent extraction of one mandibular impacted third
      molar (test), whereas the opposite tooth remained intact (control). Pre-operative
      and current-state panoramic radiographs were than scanned, and alveolar bone
      height was digitally measured on the distal aspect of the second molar on the
      test and control sides. Current-state clinical measurements were performed on
      both sides, and consisted of plaque index, gingival index, periodontal pocket
      depth, gingival margin position and clinical attachment level. Student's t-test
      for paired observations was used in order to examine the statistical significance
      of the differences in clinical parameters between the test and control sides and
      the differences in alveolar bone height pre- and post-operatively on both sides.
      Extraction of an impacted third molar resulted in a significant gain of alveolar
      bone height on the distal aspect of the adjacent second molar on the test side,
      whereas slight bone loss was noted on the control side. Even though the
      difference in plaque index between the test and control sides approached
      statistical significance following extraction, all clinical parameters seem to be
      unchanged. Further follow-up on clinical and radiological parameters is required
      for a more profound understanding of the long-term effects of third molar
      extraction on the periodontal health of the adjacent second molar.

PMID- 16098717
TI  - An intelligent tutoring system for visual classification problem solving.
AB  - OBJECTIVE: This manuscript describes the development of a general intelligent
      tutoring system for teaching visual classification problem solving. MATERIALS AND
      METHODS: The approach is informed by cognitive theory, previous empirical work on
      expertise in diagnostic problem-solving, and our own prior work describing the
      development of expertise in pathology. The architecture incorporates aspects of
      cognitive tutoring system and knowledge-based system design within the framework
      of the unified problem-solving method description language component model. Based
      on the domain ontology, domain task ontology and case data, the abstract problem
      solving methods of the expert model create a dynamic solution graph. Student
      interaction with the solution graph is filtered through an instructional layer,
      which is created by a second set of abstract problem-solving methods and
      pedagogic ontologies, in response to the current state of the student model.
      RESULTS: In this paper, we outline the empirically derived requirements and
      design principles, describe the knowledge representation and dynamic solution
      graph, detail the functioning of the instructional layer, and demonstrate two
      implemented interfaces to the system. CONCLUSION: Using the general visual
      classification tutor, we have created SlideTutor, a tutoring system for
      microscopic diagnosis of inflammatory diseases of skin.

PMID- 16098718
TI  - Human mesenchymal stem cell derived osteoblasts degrade organic bone matrix in
      vitro by matrix metalloproteinases.
AB  - Some recent studies have suggested that cells of mesenchymal origin might
      participate in the organic bone matrix dissolution. In the present study,
      collagen synthesis and degradation by human mesenchymal stem cell (MSC) derived
      cells were studied at early stage of osteoblast differentiation using a special
      two-stage in vitro culture model. In this model, cells were cultured on bovine
      bone slices, which were first resorbed by osteoclasts. Synthesis of type I
      collagen was markedly enhanced when mesenchymal cells were cultured on bone
      matrix. After thorough osteoclast removal, MSC derived cells were capable of
      degrading the organic bone matrix, and caused a release of type I collagen
      degradation product (ICTP) into the culture medium. This was inhibited by matrix
      metalloproteinase (MMP) inhibitor, while cysteine proteinase inhibitor or
      estrogen had no inhibitory effect. Western blot analysis or gelatin zymography
      confirmed the presence of MMP-2, -8, -13 and -14, but not MMP-1 or -9, in the
      differentiated cells. 17beta-Estradiol was found to increase the expression of
      MMP-2 and -14 by these cells. Finally, scanning electron microscopy showed that
      the differentiating human MSCs were capable of degrading organic bone matrix
      remnants from the bottom of the resorption lacunae. These data support the
      hypothesis that collagen cleavage by the same cells that are subsequently
      responsible for bone formation is MMP mediated process and is an important step
      coupling bone formation into bone resorption.

PMID- 16098719
TI  - Design, synthesis and bioactions of novel stable mimetics of lipoxins and aspirin
      triggered lipoxins.
AB  - The lipoxins (LX) are a class of potent endogenous oxygenated products that are
      enzymatically generated from arachidonic acid and have novel anti-inflammatory
      properties and promote resolution. Elucidation of the biochemical pathways
      involved in the metabolic inactivation of LX and the discovery of the aspirin
      triggered lipoxins (ATL) provided the basis for the design and synthesis of
      stable analogs of LX and ATL. This special issue review describes the efforts
      that led to the design and synthesis of stable LX/ATL mimetics, which permitted
      the detailed elucidation of their novel biological roles, leading to the
      development of new anti-inflammatory agents that mimic their actions. These
      synthetic molecules provided the means to uncover the physiologic roles of both
      the LX and the ATL biosynthetic pathways which led to several unexpected
      discoveries. Among these findings is the involvement of polyisoprenyl phosphates
      (PIPP) in intracellular signaling mediated by presqualene diphosphate (PSDP), and
      the recognition of the novel roles of these lipid mediators in regulating cell
      trafficking during inflammation as well as in promoting resolution of
      inflammatory processes. These efforts also provided the basis for examining the
      potential therapeutic role of LX/ATL stable mimetics and led to the development
      of new analogs with improved pharmacokinetics that opened the way to potentially
      new approaches to treating human diseases.

PMID- 16098720
TI  - 15d-Deoxy-Delta12,14-prostaglandin J2 modulates collagen type I synthesis in
      human hepatic stellate cells by inducing oxidative stress.
AB  - 15 deoxy-Delta(12,14)-prostaglandin(2) (15d-PGJ(2)) is known to inhibit the
      proliferation of hepatic stellate cells (HSCs), major cellular components that
      cause hepatic fibrosis, in vitro. It also induces oxidative stress, which results
      in hepatic myofibroblast death. On the other hand, oxidative stress generally
      induces HSC proliferation and collagen synthesis in vitro, and liver fibrogenesis
      in vivo. In this study, we evaluated the effects of 15d-PGJ(2) at various
      concentrations on the viability and collagen synthesis of HSCs. 15d-PGJ(2)
      increased intracellular reactive oxygen species (ROS), and reduced the viability
      of human HSCs at concentrations 5 microM by inducing apoptotic cell death. In
      addition, the antioxidants alpha-tocopherol and N-acetylcysteine (NAC) blocked
      15d-PGJ(2)-induced HSC death. Collagen I synthesis was increased 1.5-fold by 0.5
      microM 15d-PGJ(2) treatment, but was reduced to 30% of the control level by 10
      microM 15d-PGJ(2), and NAC pretreatment prevented these changes in collagen
      production by 15d-PGJ(2). We conclude that 15d-PGJ(2) may either induce or
      prevent hepatic fibrogenesis depending on its concentration.

PMID- 16098721
TI  - Memory T cell homeostasis and senescence during aging.
AB  - Human memory T cell pools proliferate and differentiate at varying rates that are
      determined by the frequency of lifelong antigenic re-encounter with different
      specific antigens. An important question concerning immunity is whether certain
      specific pools of memory T cells are driven to exhaustion in elderly subjects, a
      pertinent point in view of increasing human life expectancy. An emerging
      consensus is that cytomegalovirus (CMV), a beta-herpesvirus with a prevalence of
      60-90% worldwide, is an agent that induces specific T cells to extreme
      differentiation. The question that begs to be answered is whether this can
      explain why CMV seropositivity and the presence of highly differentiated CMV
      specific T cells are included in a cluster of immune parameters that have been
      shown recently to predict the early mortality of elderly humans.

PMID- 16098722
TI  - Humoral theory of transplantation: further evidence.
AB  - In the two and a half years following our initial paper on the humoral theory of
      transplantation, many publications have emerged in support of the hypothesis,
      with no studies in opposition. It is accepted that the role of antibodies is
      incontrovertible in hyperacute rejection, although what fraction of acute
      rejection is humoral remains to be determined. A recent large-scale prospective
      trial showing that transplant patients with antibodies have twice the failure
      rate as those without antibodies suggests that chronic rejection is also caused
      by antibodies. Together with serum creatinine, HLA antibodies are, therefore, the
      best predictor of graft function in kidney patients.

PMID- 16098723
TI  - T cell development and receptor diversity during aging.
AB  - The T cell system is a complex and highly dynamic system that is amazingly robust
      over many decades of human life. Its functional competence is determined not only
      by its size but also by its diversity. Homeostatic control mechanisms have to
      secure sufficient T cell replenishment while preventing loss of clonal diversity.
      Major homeostatic challenges include profound expansion and shrinkage of T cell
      clonotypes upon antigenic triggering and, more importantly, age-related changes
      in T cell regeneration. The ability of the thymus to rebuild a diverse repertoire
      ceases in the fifth decade of life. Emerging data suggest that the end of the 7th
      decade of life defines a critical time period when T cell homeostasis is no
      longer guaranteed and diversity of the naive T-cell repertoire collapses. Thus,
      failure of T cell homeostasis appears to result from cumulative defects of T cell
      generation. Elucidation of the underlying mechanisms will allow for extending
      this turning point to later in life; ultimately, interventions have to aim at
      restoring thymic function and complementary modes of T cell reconstitution.

PMID- 16098724
TI  - The role of FEV6 in the detection of airway obstruction.

PMID- 16098725
TI  - Mammalian tight junctions in the regulation of epithelial differentiation and
      proliferation.
AB  - Tight junctions are important for the permeability properties of epithelial and
      endothelial barriers as they restrict diffusion along the paracellular space.
      Recent observations have revealed that tight junctions also function in the
      regulation of epithelial proliferation and differentiation. They harbour
      evolutionarily conserved protein complexes that regulate polarisation and
      junction assembly. Tight junctions also recruit signalling proteins that
      participate in the regulation of cell proliferation and differentiation. These
      signalling proteins include components that affect established signalling
      cascades and dual localisation proteins that can associate with junctions as well
      as travel to the nucleus where they regulate gene expression.

PMID- 16098726
TI  - Cell migration in tumors.
AB  - Invasion of cancer cells into surrounding tissue and the vasculature is an
      initial step in tumor metastasis. This requires chemotactic migration of cancer
      cells, steered by protrusive activity of the cell membrane and its attachment to
      the extracellular matrix. Recent advances in intravital imaging and the
      development of an in vivo invasion assay have provided new insights into how
      cancer cell migration is regulated by elements of the local microenvironment,
      including the extracellular matrix architecture and other cell types found in
      primary tumors. These results, combined with new findings from in vitro studies,
      have led to new insights into the molecular mechanisms of cell protrusive
      activity and chemotactic migration during invasion and metastasis.

PMID- 16098727
TI  - Molecular requirements for epithelial-mesenchymal transition during tumor
      progression.
AB  - Epithelial-mesenchymal transitions (EMTs) occur as key steps during embryonic
      morphogenesis, and are now implicated in the progression of primary tumors
      towards metastases. Recent advances have fostered a more detailed understanding
      of molecular mechanisms and networks governing EMT in tumor progression. Besides
      TGFbeta and RTK/Ras signaling, autocrine factors and Wnt-, Notch-, Hedgehog- and
      NF-kappaB-dependent pathways were found to contribute to EMT. Repression of E
      cadherin by transcriptional regulators such as Snail or Twist emerges as one
      critical step driving EMT, and this stage is currently being molecularly linked
      with many of the new players. Increasing evidence suggests that EMT plays a
      specific role in the migration of cells from a primary tumor into the circulation
      and may provide a rationale for developing more effective cancer therapies.

PMID- 16098728
TI  - Dietary folate improves age-related decreases in lymphocyte function.
AB  - Although low folate status is thought to be fairly common in the older
      population, its implication on immunity has not been adequately investigated.
      Using 11-month-old and 23-month-old male rats (Fisher 344), the present study was
      undertaken to examine the modifying effects of feeding a control diet (NIH-07)
      supplemented with folate (35.7 mg/kg) for 3 weeks on the immune cells of spleen
      and mesenteric lymph node (MLN) origin. The serum concentrations of folate along
      with vitamin B(12) were elevated in response to the folate supplementation
      (P<.05). These results were accompanied by an improved proliferative response
      (stimulation index) to mitogens in both the spleen and MLNs (P<.05). The
      proportion of T cells in the MLNs, but not in the spleen, was significantly
      increased in rats fed a diet supplemented with folate. In the spleen, the folate
      supplemented diet prevented the age-associated decrease (P<.05) in the production
      of interferon (IFN)alpha by unstimulated cells and the decrease in T-helper
      (Th)1/Th2-type response after stimulation with phorbol myristate acetate and
      ionomycin. In the MLNs, on the other hand, the folate-supplemented diet failed to
      influence any age-related increase in interleukin (IL)-2, tumor necrosis factor
      alpha and IFNgamma following stimulation but did result in a significantly
      increased production of IL-4 (P<.05). Overall, this study provides data
      suggesting that aging is associated with changes in the proportion of T cells,
      the ability of immune cells to proliferate and the production of cytokines after
      stimulation. Supplementing a folate-sufficient diet with additional folate
      improves proliferative response to mitogens, the distribution of T cells in the
      MLNs and the age-related changes in cytokine production in the spleen. These
      results suggest that the dietary folate requirement may be higher in the older
      population than in the younger population to support immune functions.

PMID- 16098729
TI  - The jejunum is the main site of absorption for anthocyanins in mice.
AB  - Intestinal absorption of anthocyanins (ACNs) was studied in vitro by comparing
      ACN disappearance from the mucosal solution of Ussing chambers not containing any
      tissue (controls) and that of Ussing chambers containing segments of mouse
      duodenum, jejunum, ileum or colon. The tissues were mounted in the chambers and
      bathed with Ringer's solution (RS) adjusted to a pH representative of the
      respective segments in vivo. The chambers were kept at 37 degrees C and RS was
      perfused continuously with carbogen (95% O(2)/5% CO(2)). After the addition of an
      ACN extract to the mucosal solution, samples from both the mucosal side and the
      serosal side were withdrawn at 10, 40, 80 and 120 min and analyzed for ACN
      concentration using reversed-phase HPLC with photodiode array detection. The
      highest absorption of ACNs occurred in chambers mounted with jejunal tissue (max
      absorption rate, 55.3+/-7.6%). Minor absorption occurred with duodenal tissue
      (10.4+/-7.6%), with no absorption recorded when tissues from the ileum or colon
      were used. This study demonstrates for the first time that ACN absorption in mice
      occurs predominantly in the jejunum.

PMID- 16098730
TI  - beta-Sitosterol stimulates ceramide metabolism in differentiated Caco2 cells.
AB  - Previous studies from our laboratory on tumor cells suggest that phytosterols
      stimulate ceramide production, which was associated with cell growth inhibition
      and stimulation of apoptosis. The objective of the present study was to examine
      the effect of phytosterols on ceramide metabolism in small intestinal cells that
      represent the first cells in contact with dietary phytosterols. Caco(2) cells, an
      accepted model for human intestinal epithelial cells, were used in this study.
      Ceramide and ceramide-containing lipids were examined by labeling the ceramide
      pool with (3)H-serine. Cells were supplemented with 16 microM of sterols
      (cholesterol, beta-sitosterol or campesterol) for 16 days postconfluence and
      continued to differentiate. Of the two phytosterols, beta-sitosterol, but not
      campesterol, induced more than double the serine labeling when compared with
      cholesterol. This increase was uniform in sphingomyelin (SM), ceramide and
      sphingosine labeling. Sterols had no effect on SM concentration in the cells. In
      addition, sterol had no effect on the activity of SM synthase or
      sphingomyelinases. There was an inhibition of ceramidases with campesterol
      supplementation. These data suggest that the observed increases in SM and
      sphingosine labeling were due to an increase in ceramide turnover. The increase
      in ceramide turnover with beta-sitosterol supplementation was not associated with
      growth inhibition but was with increases in ceramide glycosylation products such
      as cerebrosides and gangliosides. It was concluded that beta-sitosterol has no
      effect on differential Caco(2), a model of normal small intestinal cells. The
      increase in the glycosylated ceramide products may offer a means to protect the
      cells from the harmful effect of ceramide by excreting them with lipoproteins.

PMID- 16098731
TI  - Limited effects of combined dietary copper deficiency/iron overload on oxidative
      stress parameters in rat liver and plasma.
AB  - Copper (Cu) deficiency decreases the activity of Cu-dependent antioxidant enzymes
      such as Cu,zinc-superoxide dismutase (Cu,Zn-SOD) and may be associated with
      increased susceptibility to oxidative stress. Iron (Fe) overload represents a
      dietary oxidative stress relevant to overuse of Fe-containing supplements and to
      hereditary hemochromatosis. In a study to investigate oxidative stress
      interactions of dietary Cu deficiency with Fe overload, weanling male Long-Evans
      rats were fed one of four sucrose-based modified AIN-93G diets formulated to
      differ in Cu (adequate 6 mg/kg diet vs. deficient 0.5 mg/kg) and Fe (adequate 35
      mg/kg vs. overloaded 1500 mg/kg) in a 2 x 2 factorial design for 4 weeks prior to
      necropsy. Care was taken to minimize oxidation of the diets prior to feeding to
      the rats. Liver and plasma Cu content and liver Cu,Zn-SOD activity declined with
      Cu deficiency and liver Fe increased with Fe overload, confirming the
      experimental dietary model. Liver thiobarbituric acid reactive substances were
      significantly elevated with Fe overload (pooled across Cu treatments, 0.80+/-0.14
      vs. 0.54+/-0.08 nmol/mg protein; P<.0001) and not affected by Cu deficiency.
      Liver cytosolic protein carbonyl content and the concentrations of several
      oxidized cholesterol species in liver tissue did not change with these dietary
      treatments. Plasma protein carbonyl content decreased in Cu-deficient rats and
      was not influenced by dietary Fe overload. The various substrates (lipid, protein
      and cholesterol) appeared to differ in their susceptibility to the in vivo
      oxidative stress induced by dietary Fe overload, but these differences were not
      exacerbated by Cu deficiency.

PMID- 16098732
TI  - Pro-oxidative effect of beta-carotene and the interaction with flavonoids on UVA
      induced DNA strand breaks in mouse fibroblast C3H10T1/2 cells.
AB  - It has been suggested that beta-carotene itself is unstable under certain
      conditions and that a combination of antioxidants may prevent the pro-oxidative
      effects of beta-carotene. Thus, the present study aimed to investigate the
      interaction of beta-carotene with three flavonoids-naringin, rutin and quercetin
      on DNA damage induced by ultraviolet A (UVA) in C3H10T1/2 cells, a mouse embryo
      fibroblast. The cells were preincubated with beta-carotene and/or flavonoid for 1
      h followed by UVA irradiation, and DNA damage was measured using comet assay. We
      showed that beta-carotene at 20 microM enhanced DNA damage (by 35%; P<.05)
      induced by UVA (7.6 kJ/m2), whereas naringin, rutin and quercetin significantly
      decreased UVA-induced DNA damage. When each flavonoid was combined with beta
      carotene during preincubation, UVA-induced cellular DNA damage was significantly
      suppressed and the effects were in the order of naringin > or = rutin >
      quercetin. The flavonoids decreased UVA-induced oxidation of preincorporated beta
      carotene in the same order. Using electron spin resonance spectroscopy, we showed
      that the ability of these flavonoids to quench singlet oxygen was consistent with
      protection against DNA damage and beta-carotene oxidation. All three flavonoids
      had some absorption at the UVA range (320-380 nm), but the effects were opposite
      to those on DNA damage and beta-carotene oxidation. Taken together, this cell
      culture study demonstrates an interaction between flavonoids and beta-carotene in
      UVA-induced DNA damage, and the results suggest that a combination of beta
      carotene with naringin, rutin or quercetin may increase the safety of beta
      carotene.

PMID- 16098733
TI  - Serum equol, bone mineral density and biomechanical bone strength differ among
      four mouse strains.
AB  - The extent of conversion of daidzein to its metabolite, equol, by intestinal
      microflora may be a critical step that determines if a diet rich in daidzein
      protects against the deterioration of bone after estrogen withdrawal. The
      objective was to determine the extent that daidzein is converted to equol. In
      addition, bone mineral content (BMC), bone mineral density (BMD) and strength of
      femurs and lumbar vertebrae (LV) in four mouse strains were measured. Mice were
      ovariectomized and fed control diet (AIN93G) with or without daidzein (200 mg
      daidzein/kg diet) for 3 weeks, after which serum, femurs and LV were collected.
      Serum daidzein and equol were elevated in all mice fed daidzein. Among mice fed
      daidzein, the CD-1 and Swiss-Webster (SW) mice had higher (P<.001) serum equol
      than C57BL/6 (C57) and C3H mice. Differences due to mouse strain were observed
      for all bone outcomes. C57 mice had lower femur BMC (P<.001), BMD (P<.001) and
      peak load at femur midpoint (P<.001) and neck (P<.001) than other mouse strains.
      C57 mice also had a lower femur midpoint yield load (P<.001) and resilience
      (P<.001) than C3H mice. C57 mice had a lower LV1-4 BMC (P<.001) and BMD (P<.001)
      compared with all mouse strains and peak load of LV3 was lower than CD-1 and SW
      mice. Differences in serum equol, BMD and bone strength properties should be
      considered when selecting a mouse strain for investigating whether dietary
      strategies that include isoflavones preserve bone tissue after ovariectomy.

PMID- 16098734
TI  - Chronic administration of ethyl docosahexaenoate reduces gerbil brain eicosanoid
      productions following ischemia and reperfusion.
AB  - Arachidonic acid (AA) and its vasoactive metabolites have been implicated in the
      pathogenesis of brain damage induced by cerebral ischemia. The membrane AA
      concentrations can be reduced by changes in dietary fatty acid intake. The
      purpose of the present study was to investigate the effects of chronic ethyl
      docosahexaenoate (E-DHA) administration on the generation of eicosanoids of AA
      metabolism during the period of reperfusion after ischemia in gerbils. Weanling
      male gerbils were orally pretreated with either E-DHA (100, 200 mg/kg) or
      vehicle, once a day, for 10 weeks, and subjected to transient forebrain ischemia
      by bilateral common carotid occlusion for 10 min. E-DHA (200 mg/kg) pretreatment
      significantly decreased the content of brain lipid AA at the termination of
      treatment, prevented postischemic impaired regional cerebral blood flow (rCBF)
      and reduced the levels of brain prostaglandin (PG) PGF(2alpha) and 6-keto
      PGF(1alpha), and thromboxane B(2) (TXB(2)), as well as leukotriene (LT) LTB(4)
      and LTC(4) at 30 and 60 min of reperfusion compared with the vehicle, which was
      well associated with the attenuated cerebral edema in the E-DHA-treated brain
      after 48 h of reperfusion. These data suggest that the E-DHA (200 mg/kg)
      pretreatment reduces the postischemic eicosanoid productions, which may be due to
      its reduction of the brain lipid AA content.

PMID- 16098735
TI  - Effective management of municipal solid waste (MSW).

PMID- 16098736
TI  - Electrochemical biosensing based on universal affinity biocomposite platforms.
AB  - Rigid conducting biocomposites are versatile and effective transducing materials
      for the construction of a wide range of amperometric biosensors such as
      immunosensors, genosensors and enzymosensors, particularly if the transducer is
      bulk-modified with universal affinity biomolecules. The strept(avidin)-graphite
      epoxy biocomposite could be considered as an universal immobilization platform
      whereon biotinylated DNAs, oligonucleotides, enzymes or antibodies can be
      captured by means of the highly affinity (strept)avidin-biotin reaction.
      Universal affinity biocomposite-based biosensors offer many potential advantages
      compared to more traditional electrochemical biosensors commonly based on a
      biologically surface-modified transducer. The integration of many materials into
      one matrix is their main advantage. As biological bulk-modified materials, the
      conducting biocomposites act not only as transducers, but also as reservoir for
      the biomaterial. After its use, the electrode surface can be renewed by a simple
      polishing procedure, establishing a clear advantage of these approaches relative
      to classical biosensors and other common biological assays. Moreover, the same
      material is useful for the analysis of many molecules whose determinations are
      based on genetic, enzymatic or immunological reactions. The different strategies
      for electrochemical genosensing, immunosensing and enzymosensing, all of them
      being dependent on the presence of a redox enzyme marker for the generation of
      the electrochemical signal, based on this universal affinity biocomposite
      platform are all presented and discussed.

PMID- 16098737
TI  - Bioengineering the hair follicle: fringe benefits of stem cell technology.
AB  - Recent advances in epithelial stem cell biology have resulted in the isolation of
      hair follicle stem cells, which generate hair follicles when injected into
      immunodeficient mice. These isolated hair follicle epithelial stem cells must be
      combined with 'inductive' dermal cells to produce new hair follicles. The advent
      of techniques for cultivating inductive dermal cells and competent epithelial
      stem cells creates the opportunity to bioengineer hair follicles for the
      treatment of hair loss.

PMID- 16098738
TI  - DNA methylation and histone modifications: teaming up to silence genes.
AB  - DNA methylation, histone deacetylation, and methylation of histone H3 at lysine 9
      are the three best-characterized covalent modifications associated with a
      repressed chromatin state. Recent advances highlight an essential, intricate web
      of interactions among these processes, generating a self-reinforcing, self
      perpetuating cycle of epigenetic events that lead to long-term transcriptional
      repression. Histone deacetylation and methylation at lysine 9 of H3 might also
      contribute to the establishment of DNA methylation patterns, a long-standing
      mystery in epigenetics. What's more, recent clues suggest a potential link
      between CpG methylation and other histone modifications. A complex picture is
      emerging in which DNA methylation and histone modifications work hand-in-hand as
      parts of an epigenetic program that integrates gene-silencing networks within the
      cell.

PMID- 16098739
TI  - Molecularly targeted agents: their promise as cancer chemopreventive
      interventions.
AB  - Molecular medicine has fully entered in to the oncology arena. The development of
      targeted therapies is one of the major ongoing efforts in cancer treatment.
      Targeted therapy refers to treatment strategies directed against molecular
      targets considered to be involved in neoplastic transformation. Such molecularly
      targeted agents (MTA) are currently under study in all treatment settings
      including that of chemoprevention, defined as the use of natural or synthetic
      agents to interrupt the carcinogenic process, to nip tumours in the bud. This
      review article aims to provide a general overview of the potential use of some of
      these MTA in the chemoprevention setting.

PMID- 16098740
TI  - Lime treatment of keratinous materials for the generation of highly digestible
      animal feed: 1. Chicken feathers.
AB  - Chicken feather keratin was treated with lime (calcium hydroxide) to obtain a
      liquid product rich in amino acids and polypeptides that can be used as an animal
      feed supplement. The effect of treatment conditions and the properties of the
      soluble keratin were studied. At high temperatures (150 degrees C), 80% of
      feather keratin was solubilized within 25 min, whereas a relatively longer
      reaction time (300 min) is needed at moderate temperatures (100 degrees C). After
      3h of hydrolysis at 150 degrees C, 95% of feather keratin was digested. For the
      recommended conditions (100 degrees C, 300 min, and 0.1g Ca(OH)(2)/g dry
      feather), after lime treatment, about 54% of calcium can be recovered by
      carbonating. In rumen fluid, ammonia production from soluble keratin was similar
      to that of soybean and cottonseed meals and was greatly less than that of urea,
      indicating that no ammonia toxicity will result from cattle being fed soluble
      keratin.

PMID- 16098741
TI  - ERbeta ligands. Part 4: Synthesis and structure-activity relationships of a
      series of 2-phenylquinoline derivatives.
AB  - A new class of estrogen receptor beta (ERbeta) ligands based on the 2
      phenylquinoline scaffold was prepared. Several analogues with C4 substitution
      displayed high affinity (3-5 nM) and significant selectivity (up to 83-fold) for
      ERbeta. The best compound, 13b, was profiled as a selective partial agonist for
      ERbeta at 1 muM in a cell-based transcriptional assay. Uterine weight bioassay of
      13b indicated no activation of ERalpha in vivo.

PMID- 16098742
TI  - Potent and orally active non-peptide antagonists of the human melanocortin-4
      receptor based on a series of trans-2-disubstituted cyclohexylpiperazines.
AB  - The melanocortin-4 receptor (MC4R) plays an important role in the regulation of
      energy homeostasis. Recent studies have shown that blockade of the MC4R reverses
      tumor-induced weight loss in mice. Herein, we describe the synthesis and
      identification of potent and selective non-peptide antagonists of the human MC4R
      from a series of 2-ethoxycarbonylcyclohexyl-piperazines. Compound 12i was found
      to possess low nanomolar affinity for the MC4R, and exhibit oral bioavailability
      in rats. More importantly, when administered orally to mice (10 mg/kg), it led to
      statistically significant increases in food intake over a 24-h period.

PMID- 16098743
TI  - Reactions of alpha-hydroxyethyl radicals with flavonoids of various structures.
AB  - It has been found that flavonoids (FL) are able to reduce, add or oxidize alpha
      hydroxyethyl radicals (HER). The probability of these processes to occur depends
      on the structure of the FL under study. Namely, to cause reduction of HER, the
      presence of hydroxyl groups is necessary, and to effect oxidation or addition of
      HER, the presence of a carbonyl group at C4 and a C2-C3 double bond in the C ring
      is required.

PMID- 16098744
TI  - 4-Phenyl-1,2,3,6-tetrahydropyridine, an excellent fragment to improve the potency
      of PARP-1 inhibitors.
AB  - We have shown that a 4-phenyl-1,2,3,6-tetrahydropyridine fragment plays an
      important role in improving inhibitory potency against poly(ADP-ribose)
      polymerase-1 (PARP-1). Various benzamide analogues linked with this fragment via
      alkyl spacers have been prepared and evaluated. As a result, some of them have
      been found to be highly potent PARP-1 inhibitors.

PMID- 16098745
TI  - Aging affects coordination of rapid head motions with trunk and pelvis movements
      during standing and walking.
AB  - The head, containing the gravity sensors (vestibular system) and the visual
      system, must be stabilized in space to provide a steady reference. During
      walking, the head also needs to be free to move to allow scanning of surrounding
      objects and steering of locomotion. With aging, deteriorations in motor and
      sensory systems and their integration are commonly observed. Nevertheless, the
      strategies used by elderly subjects to complete challenging tasks that require
      precise sensorimotor integration, such as turning the head rapidly during gait,
      is not known. The objective of this study was to determine the effects of aging
      on the movement coordination of the head, trunk and pelvis when executing a rapid
      head motion in response to a visual signal. Elderly and young subjects turned
      their head rapidly (up, down, left, right or none) in response to a visual
      signal, during standing and walking. The 3-D positions of head, trunk and pelvis
      were recorded and analyzed. All subjects, young and old, successfully performed
      the task during both standing and walking without any loss of balance. Postural
      stability was maintained as large head motions were accompanied by relatively
      small trunk and pelvis movements. Horizontal plane movements associated with
      right and left head turns were significantly larger than sagittal plane movements
      associated with head up and down motions. Head motions were significantly slower
      and smaller in elderly subjects, and resulted in disrupted horizontal plane trunk
      pelvis coordination during walking. We conclude that head, trunk and pelvis
      movements are coordinated in a task-dependent manner such that their movement
      amplitudes induced by rapid voluntary head motions are larger in walking than in
      standing. This task-dependent movement coordination is affected by aging.

PMID- 16098746
TI  - Middle-old and old-old retirement dwelling adults respond differently to
      locomotor challenges in cluttered environments.
AB  - Obstacle navigation during locomotion was investigated in older adults using an
      obstacle course paradigm under different ambient lighting conditions. Similar
      strategies for obstacle navigation were observed between the two age groups
      studied (middle-old: 75-85 years and old-old adults: 85 years and older), however
      old-old individuals were "less" successful at avoiding obstacles. Differences
      observed between the two age groups in obstacle course performance may be
      attributed to changes in spatial reference frames that occur with age and/or
      differences in perceived threat of obstacles in the travel path. Reduced lighting
      conditions and increasing age were also found to have significant affects on
      obstacle navigation.

PMID- 16098747
TI  - Using induced accelerations to understand knee stability during gait of
      individuals with muscle weakness.
AB  - The purpose of this case series was to quantify the effectiveness of different
      compensatory strategies used by individuals with muscle weakness to produce knee
      extension during the stance phase gait. Subjects were three males with less than
      anti-gravity strength in the quadriceps femoris and a variable pattern of
      weakness elsewhere in the lower extremity. They walked independently at a self
      selected speed without assistive devices. Gait analysis of the pelvis and
      bilateral lower extremity segments was performed with a six-camera, two force
      platform motion capture system. Joint angles and net internal moments were
      computed from the motion data. Induced acceleration analysis was performed to
      quantify the relative ability of each lower extremity joint moment and gravity to
      produce knee angular acceleration. Results showed that a variety of adaptive
      strategies both within and across limbs can control knee position during gait.
      One subject generated knee extension almost exclusively via the hip extensor
      moment. Another relied less on the hip extensor moment (39%) and more on the
      ankle plantar flexor moment (61%) to create knee extension. The third subject
      used the ipsilateral hip extensor moment (24%) and the contralateral ankle
      plantar flexor moment (67%) to assist knee extension. The strategy selected by
      each subject likely was influenced by both their total pattern of impairments and
      the effectiveness of the available compensations. This case series demonstrates
      how an induced acceleration analysis can augment a traditional gait analysis to
      expand and enhance our understanding of compensatory movement control strategies.

PMID- 16098748
TI  - Bilateral subthalamic stimulation improves gait initiation in patients with
      Parkinson's disease.
AB  - Impaired gait initiation is one of the typical sign of advanced Parkinson's
      disease (PD). This is the first study to examine quantitatively the effect of
      deep brain stimulation of the subthalamic nucleus on the performance of gait
      initiation for patients with advanced PD. A total of 11 patients after surgery of
      bilateral deep brain stimulation of the subthalamic nucleus (STN) were tested in
      both the deep brain stimulation (DBS) ON and OFF conditions and/or in both the
      medication ON (i.e., with the usual dosage of antiparkinsonian medications
      administered) and OFF (i.e., with the usual dosage of antiparkinsonian
      medications withheld) conditions. DBS had no effect on the onset of anticipatory
      postural adjustment (APA). The effect of DBS approached significant level for the
      onset of swing foot lifting, but reached significant level for the delay of swing
      foot lifting. DBS significantly increased the amplitude of the APA, amplitude of
      reactive shear forces on both feet, and amplitude of COP in both anterior
      posterior and medial-lateral directions. It is concluded that DBS significantly
      improved the performance of patients with advanced PD in gait initiation.

PMID- 16098749
TI  - An improved powered ankle-foot orthosis using proportional myoelectric control.
AB  - We constructed a powered ankle-foot orthosis for human walking with a novel
      myoelectric controller. The orthosis included a carbon fiber and polypropylene
      shell, a metal hinge joint, and two artificial pneumatic muscles. Soleus
      electromyography (EMG) activated the artificial plantar flexor and inhibited the
      artificial dorsiflexor. Tibialis anterior EMG activated the artificial
      dorsiflexor. We collected kinematic, kinetic, and electromyographic data for a
      naive healthy subject walking with the orthosis. The current design improves upon
      a previous prototype by being easier to don and doff and simpler to use. The
      novel controller allows naive wearers to quickly adapt to the orthosis without
      artificial muscle co-contraction. The orthosis may be helpful in studying human
      walking biomechanics and assisting patients during gait rehabilitation after
      neurological injury.

PMID- 16098750
TI  - Rapid fluctuations in conscious state in a patient with an extensive spinal dural
      fistula.
AB  - A man with a spontaneous spinal dural fistula and significant fluctuations in
      level of consciousness is discussed. The presentation was that of headache and
      vomiting followed by an initially enigmatic acute reduction in the level of
      consciousness. This required urgent evacuation of bilateral chronic subdural
      haematomas, believed to be causative. Following mobilisation, several episodes of
      presumed orthostatic intracranial hypotension occurred rendering the patient
      rapidly unconscious. A large spinal extradural CSF collection extending through
      the full length of the vertebral canal was later diagnosed however, the precise
      location of the fistulous leak could not be found radiologically. Non-operative
      management was successful. To the best of our knowledge, this is the first
      description of a spontaneous spinal cerebrospinal fluid leak of this magnitude.
      The case, pathogenesis, investigations and management of this rare entity are
      considered and the literature reviewed.

PMID- 16098751
TI  - Spinal ossifying lipoma.
AB  - A case of ossifying spinal lipoma is reported. The patient presented with a large
      swelling over the lumbar region with a dermal sinus in the centre. Imaging
      revealed an intradural lipoma connected with a large subcutaneous lipoma in which
      there was a prominent island of bone. The lipoma was excised and there were no
      postoperative neurological deficits. To the best of our knowledge, this is the
      first report of a spinal ossifying lipoma associated with a dermal sinus.

PMID- 16098752
TI  - A tumor in the medulla oblongata producing beta-HCG and AFP.
AB  - A 23 year-old woman presented with dysarthria, hoarseness, dysphasia, ataxia and
      dyspnoea. MRI showed a mass of heterogeneous intensity at the dorsal medulla
      oblongata. Laboratory studies revealed high serum alpha-fetoprotein (AFP) and
      beta-subunit human chorionic gonadotropin (beta-HCG) levels. No other tumours
      were found on systemic investigation. An intracranial non-germinomatous germ cell
      tumour (NGGCT) was strongly suspected. The patient received combination
      chemotherapy using ifosfamide, cisplatin, and etoposide and local irradiation to
      a total of 52 Gy. Serum AFP and beta-HCG levels normalized after four cycles of
      chemotherapy and she became asymptomatic apart from mild postural hypotension. A
      follow-up MRI showed only a tiny residual lesion in the medulla oblongata, which
      has been stable for more than three years. Surgical resection should be carefully
      considered in patients with brainstem tumours with elevation of serum tumour
      markers as chemo- and radiotherapy may be effective for brainstem NGGCT.

PMID- 16098753
TI  - A case of presumptive primary lateral sclerosis with upper and lower motor
      neurone pathology.
AB  - Motor Neurone Disease (MND) is one of the commonest neurodegenerative disorders
      of adulthood. MND characteristically presents with a combination of both upper
      and lower motor neurone features. Primary Lateral Sclerosis (PLS) is thought to
      be a variant of MND presenting with purely upper motor neurone signs. Debate
      continues over whether PLS constitutes a distinct pathological entity or whether
      it is part of the spectrum of motor neurone diseases that present as an upper
      motor neurone-predominant form of MND. We present a case of MND with purely upper
      motor neurone features and a prominent pain component. A pre-mortem diagnosis of
      PLS was made, however autopsy findings demonstrated both upper and lower motor
      neurone involvement. We believe these findings support the view that PLS is not a
      discrete pathological entity, but that it is a part of the range of motor neurone
      diseases that present with predominant but not exclusive upper motor neurone
      involvement. This case also highlights the feature that pain may be associated
      with MND even though it is not appreciated to have a sensory pathology.

PMID- 16098754
TI  - Marjolin's ulcer of the scalp invading calvarial bone, dura and brain.
AB  - A Marjolin's ulcer arising in a chronic scalp scar is reported. Malignant
      transformation occurred after four decades. The tumour had invaded the skull,
      dura mater and underlying brain tissue. This case illustrates the importance of
      appropriate and expeditious initial wound management of scar ulcers with high
      malignant potential to prevent this devastating outcome and also the role of
      reconstructive surgical techniques in radical surgery for scalp cancers.

PMID- 16098755
TI  - Isolated pineal region metastasis of small cell lung cancer.
AB  - The pineal region is an unusual site for brain metastasis and most metastatic
      pineal lesions are asymptomatic. Rarely the symptoms of metastatic involvement of
      the pineal gland precede those of the primary tumor or other metastatic sites. An
      83 year-old man presented with gait disturbance and limitation of upward gaze.
      Brain MRI showed homogeneous enhancement of a solitary mass in the pineal region
      with obstructive hydrocephalus. A stereotactic biopsy was performed, and small
      cell carcinoma was diagnosed. A systemic investigation for the primary lesion
      subsequently revealed small cell carcinoma of the lung. The patient was referred
      for radiotherapy and chemotherapy. Although rare, metastatic tumor should be
      considered in the differential diagnosis of pineal region tumors, particularly in
      elderly patients.

PMID- 16098756
TI  - Clinical and histopathological analysis of cystic meningiomas.
AB  - Between 1993 and 2003, we treated 21 patients with cystic meningioma (of 365 with
      meningioma, 5.5%). We grouped these patients according to classifications by
      Nauta and Rengachary and analyzed them by gender, age, tumor location, clinical
      manifestations, MRI features and histopathology. The mean duration of symptoms
      was relatively short at 1.6 months. There were five atypical and 16 benign
      meningiomas on histopathology. In type I and II cystic meningiomas, with
      intratumoral cysts, all cyst walls enhanced on MRI and had tumor cells in the
      cyst wall on histopathology. In type III and IV cystic meningiomas, with
      peritumoral cysts, the cyst wall did not enhance on MRI and only one case (type
      III) had tumor cells in the cyst wall on histopathology. We suggest that when the
      cyst wall shows contrast enhancement on imaging, the cyst wall should be
      completely removed at surgery. If there is no contrast enhancement, multiple
      biopsies of the cyst wall should be taken to assess the presence of tumor cells
      in the cyst wall.

PMID- 16098757
TI  - Cerebral autoregulation and ageing.
AB  - Little is known about the effects of ageing on cerebral autoregulation (CA). To
      examine the relationship between age and CA in adults, we conducted a prospective
      study using a non-invasive protocol without external stimuli. We studied 32
      subjects, aged 23-68 years. They were assigned to a young group (28+/-5 years)
      and an old group (54+/-8 years). The groups were sex-matched. Transcranial
      Doppler ultrasonography (TCD) was used to record bilateral middle cerebral artery
      flow velocities (CBFV, cm/sec). Noninvasive beat-to-beat tonometric arterial
      blood pressure (ABP) measurement of the radial artery was used to record
      spontaneous blood pressure fluctuations. The Mx, an index of dynamic cerebral
      autoregulation (dCA), was calculated from a moving correlation between ABP and
      CBFV. We did not find a correlation between age and Mx. No statistically
      significant difference in the Mx between the groups (0.27+/-0.23, young, vs.
      0.37+/-0.24, old) was demonstrated. Age does not affect dynamic cerebral
      autoregulation assessed by the Mx index in healthy adult subjects. This study
      supports findings from previous papers wherein CA was measured with protocols
      which require external stimuli. Further studies are needed to determine CA in
      subjects above 70 years of age.

PMID- 16098758
TI  - Thalamotomy versus thalamic stimulation for multiple sclerosis tremor.
AB  - Disabling intractable tremor occurs frequently in patients with multiple
      sclerosis (MS). There is currently no effective medical treatment available, and
      the results of surgical intervention have been variable. Thalamotomy has been the
      mainstay of neurosurgical therapy for intractable MS tremor, however the
      popularisation of deep brain stimulation (DBS) has led to the adoption of chronic
      thalamic stimulation in an attempt to ameliorate this condition. With the goal of
      examining the relative efficacy and adverse effects of these two surgical
      strategies, we studied twenty carefully selected patients with intractable MS
      tremor. Thalamotomy was performed in 10 patients, with chronic DBS administered
      to the remaining 10. Both thalamotomy and thalamic stimulation produced
      improvements in postural and intention tremor. The mean improvement in postural
      tremor at 16.2 months following surgery was 78%, compared with a 64% improvement
      after thalamic stimulation (14.6 month follow-up) (P > 0.05). Intention tremor
      improved by 72% in the group undergoing thalamotomy, a significantly larger gain
      than the 36% tremor reduction following DBS (P < 0.05). Early postoperative
      complications were common in both groups. Permanent complications related to
      surgery occurred in four patients overall. Following thalamotomy, long-term
      adverse effects were observed in three patients (30%), and comprised hemiparesis
      and seizures. Only one patient in the thalamic stimulation group experienced a
      permanent deficit (monoparesis). We conclude that thalamotomy is a more
      efficacious surgical treatment for intractable MS tremor, however the higher
      incidence of persistent neurological deficits in patients receiving lesional
      surgery may support the use of DBS as the preferred surgical strategy.

PMID- 16098759
TI  - Central actions of adipocyte hormones.
AB  - Adipose tissue secretes a variety of proteins with important roles in metabolism,
      reproduction, immunity and cardiovascular function. The endocrine function of
      adipose tissue, especially that of leptin, is linked to energy storage and thus
      might provide insights into obesity and other diseases associated with energy
      imbalance. This review highlights the current understanding of the actions of
      leptin in the brain, with particular emphasis on transport across the blood-brain
      barrier, signal transduction, neuropeptide targets and roles during fasting and
      obesity. Moreover, data pertaining to the potential central effects of
      adiponectin, cytokines and resistin on energy homeostasis, glucose and lipid
      metabolism are discussed.

PMID- 16098760
TI  - Effect of lyophilised Vaccinium berries on memory, anxiety and locomotion in
      adult rats.
AB  - Epidemiological studies suggest that diets with a high intake of vegetables and
      fruits may reduce the incidence of degenerative disorders including Alzheimer's
      disease. Berries are some of the popular fruits consumed worldwide. They are
      considered to be rich in anthocyanin pigments, a group belonging to the
      flavonoids, a widespread class of phenolic compounds. Anthocyanins have notorious
      pharmacological properties, and have been used in humans for therapeutic
      purposes. The present experiments were performed to study the possible effects of
      prolonged administration of lyophilised Vaccinium berries (blueberry, bilberry)
      on cognitive performance using step-down inhibitory avoidance, open field,
      elevated plus-maze, and radial maze tasks. During this experiment the rats
      consumed approximately 3.2 mg kg(-1)day (oral), of the anthocyanins. The
      lyophilised berries were administered for 30 days before first training. The
      present study showed that lyophilised berries significantly enhanced short-term
      memory, but not long-term memory in the inhibitory avoidance task, and induced an
      increase in the number of crossings in the first exposure to the open field.
      However, treated rats did not present any improvement of memory retention in open
      field habituation. Additionally, prolonged treatment with lyophilised berries did
      not have any significant effects in the elevated plus-maze task. Another
      interesting finding was that lyophilised berries improved working memory in the
      radial maze, with significant differences observed during sessions 1-2 and 4, but
      did not alter reference memory in this task. These results suggest that
      lyophilised berries may be beneficial in the prevention of memory deficits, one
      of the symptoms related to AD, and corroborate previous findings showing that
      flavonoids present effects in several learning paradigms.

PMID- 16098761
TI  - Differences in the regenerative response of neuronal cell populations and
      indications for plasticity in intraspinal neurons after spinal cord transection
      in adult zebrafish.
AB  - In zebrafish, the capacity to regenerate long axons varies among different
      populations of axotomized neurons after spinal cord transection. In specific
      brain nuclei, 84-92% of axotomized neurons upregulate expression of the growth
      related genes GAP-43 and L1.1 and 32-51% of these neurons regrow their descending
      axons. In contrast, 16-31% of spinal neurons with axons ascending to the
      brainstem upregulate these genes and only 2-4% regrow their axons. Dorsal root
      ganglion (DRG) neurons were not observed to regrow their ascending axons or to
      increase expression of GAP-43 mRNA. Expression of L1.1 mRNA is high in unlesioned
      and axotomized DRG neurons. In the lesioned spinal cord, expression of growth
      related molecules is increased in a substantial population of non-axotomized
      neurons, suggesting morphological plasticity in the spinal-intrinsic circuitry.
      We propose that locomotor recovery in spinal-transected adult zebrafish is
      influenced less by recovery of ascending pathways, but more by regrowth of
      descending tracts and rearrangement of intraspinal circuitry.

PMID- 16098762
TI  - Optimisation of a human neutrophil elastase assay and investigation of the effect
      of sesquiterpene lactones.
AB  - Neutrophil granulocytes are effector cells in innate and humoral immunity. They
      are involved in inflammatory processes by releasing pro-inflammatory enzymes,
      such as the human neutrophil elastase (HNE). We here report an optimisation of an
      HNE release assay using microplates. Special attention has been directed to
      overcome the often observed activation of neutrophils during isolation from fresh
      blood. This so-called basal stimulation can take place without addition of
      external stimulants and can cause severe problems during the assay. We
      demonstrated that bovine serum albumin (BSA), lipopolysaccharide (LPS), use of
      different blood donors, heparin and ethylenediaminetetraacetic acid (EDTA) do not
      cause basal stimulation, but may be due to mechanical stress and the immune
      system of the blood donor. Here, the number of eosinophils may play a role in the
      induction of activation. Basal stimulation was overcome when a hypertonic
      solution, such as sucrose- with N-(2-hydroxyethyl)-piperazine-N'-2-ethanesulfonic
      acid (HEPES) buffer, was used during centrifugation and the isolated granulocytes
      were left in phosphate buffered saline (PBS) for 30 min before stimulation.
      Sesquiterpene lactones (SLs), known for their anti-inflammatory activity were
      used for evaluation of the assay and were observed to inhibit HNE release at
      micromolar concentrations. Whereas N-formyl-methionyl-leucylphenylalanine (fMLP),
      platelet-activating factor (PAF) and basal stimulation resulted in similar IC50
      values, phorbol-12-myristate-13-acetate (PMA) as a stimulant needed higher
      concentrations of SLs. The molecular inhibitory mechanism of SLs is discussed.

PMID- 16098763
TI  - Quantification of acetylation at proximal lysine residues using isotopic labeling
      and tandem mass spectrometry.
AB  - With the emergence of the histone code as a key determinant in the regulation of
      gene expression, it has been important to develop tools that can not only
      identify the types and locations of myriad modifications, but also determine how
      the levels of these modifications change as a result of various processes in a
      cell. Mass spectrometry has become a method of choice for the investigation of
      post-translational modifications in histone proteins. Described in this article
      is a mass spectrometric method that is useful for direct quantification of levels
      of acetylation at lysines residues in close proximity to one another, as is the
      case for the amino terminal tail of histone H4. This method involves
      fragmentation of peptides into b and y ions that contain one or more sites of
      modification and isotopic labeling which ensures equivalent ionization and
      fragmentation.

PMID- 16098764
TI  - White shrimp (Litopenaeus vannamei) recombinant lysozyme has antibacterial
      activity against Gram negative bacteria: Vibrio alginolyticus, Vibrio
      parahemolyticus and Vibrio cholerae.
AB  - C-type lysozyme has been described as an antibacterial component of the shrimp
      innate defence system. We determined quantitatively the antibacterial activity of
      white shrimp (Litopenaeus vannamei) recombinant lysozyme against three Gram
      negative bacteria: Vibrio alginolyticus, Vibrio parahemolyticus and Vibrio
      cholerae, using a turbidimetric assay with live bacteria and differential
      bacterial viable count after interaction with the protein. In conclusion, the
      antibacterial activity of recombinant shrimp lysozyme against Vibrio sp. is at
      least equal to the values against the Gram positive M. luteus and more active
      against the shrimp pathogens V. alginolyticus and V. parahemolyticus.

PMID- 16098765
TI  - The self in action: lessons from delusions of control.
AB  - Patients with delusions of control are abnormally aware of the sensory
      consequences of their actions and have difficulty with on-line corrections of
      movement. As a result they do not feel in control of their movements. At the same
      time they are strongly aware of the action being intentional. This leads them to
      believe that their actions are being controlled by an external agent. In
      contrast, the normal mark of the self in action is that we have very little
      experience of it. Most of the time we are not aware of the sensory consequences
      of our actions or of the various subtle corrections that we make during the
      course of goal-directed actions. We know that we are agents and that we are
      successfully causing the world to change. But as actors we move through the world
      like shadows glimpsed only occasional from the corner of an eye.

PMID- 16098766
TI  - Cerebral perfusion abnormality in narcolepsy with cataplexy.
AB  - To investigate abnormal cerebral perfusion in narcoleptics with cataplexy, 25
      narcoleptics with cataplexy and 25 normal controls were enrolled in this study.
      Cerebral perfusion was measured by brain single photon emission computed
      tomography (SPECT) using 99mTc-ethylcysteinate dimer. Patients and normal
      controls had not received any medication prior to the SPECT scan. Differences in
      cerebral perfusion between narcoleptics and normal controls were subjected to
      statistical parametric mapping (SPM) analysis. Overnight polysomnography and
      multiple sleep latency test (MSLT) were performed in all patients. Brain SPECT
      was carried out on all patients and normal controls during the waking state.
      Clinical symptoms and MSLT results of all patients are in accord with the
      International Classification of Sleep Disorders criteria for narcolepsy. MSLT
      showed a short mean sleep latency (1.69 +/- 1.0 min) and 2-5 sleep onset REM
      periods in individual patient. SPM analysis of brain SPECT showed hypoperfusion
      of the bilateral anterior hypothalami, caudate nuclei, and pulvinar nuclei of
      thalami, parts of the dorsolateral/ventromedial prefrontal cortices,
      parahippocampal gyri, and cingulate gyri in narcoleptics [P < 0.05 by Student's t
      test with false discovery rate (FDR) correction]. Significant hypoperfusion in
      the white matter of frontal and parietal lobes was also noted in narcoleptics.
      This study shows reduced cerebral perfusion in subcortical structures and
      cortical areas in narcoleptics. The distribution of abnormal cerebral perfusion
      is concordant with the pathway of the cerebral hypocretin system and may explain
      the characteristic features of narcolepsy, i.e., cataplexy, emotional lability,
      and attention deficit.

PMID- 16098767
TI  - Evolutionary history of the greater white-toothed shrew (Crocidura russula)
      inferred from analysis of mtDNA, Y, and X chromosome markers.
AB  - We investigate the evolutionary history of the greater white-toothed shrew across
      its distribution in northern Africa and mainland Europe using sex-specific (mtDNA
      and Y chromosome) and biparental (X chromosome) markers. All three loci confirm a
      large divergence between eastern (Tunisia and Sardinia) and western (Morocco and
      mainland Europe) lineages, and application of a molecular clock to mtDNA
      divergence estimates indicates a more ancient separation (2.25 M yr ago) than
      described by some previous studies, supporting claims for taxonomic revision.
      Moroccan ancestry for the mainland European population is inconclusive from
      phylogenetic trees, but is supported by greater nucleotide diversity and a more
      ancient population expansion in Morocco than in Europe. Signatures of rapid
      population expansion in mtDNA, combined with low X and Y chromosome diversity,
      suggest a single colonization of mainland Europe by a small number of Moroccan
      shrews >38 K yr ago. This study illustrates that multilocus genetic analyses can
      facilitate the interpretation of species' evolutionary history but that
      phylogeographic inference using X and Y chromosomes is restricted by low levels
      of observed polymorphism.

PMID- 16098768
TI  - A phylogenetic analysis of Pseudonaja (Hydrophiinae, Elapidae, Serpentes) based
      on mitochondrial DNA sequences.
AB  - A phylogenetic analysis of mitochondrial ND4 and adjacent tRNA sequences for a
      geographically extensive series of specimens reveals nine major clades within
      Pseudonaja, of which six are largely coincident with nominal taxa (P. affinis, P.
      guttata, P. inframacula, P. ingrami, P. modesta, and P. textilis). The remaining
      three clades are composed of specimens presently referred to P. nuchalis. Two of
      these clades correspond with the "Darwin" and "Southern" morphs of previous
      authors, while the third clade incorporates the "Orange with black head" and
      "Pale head, grey nape" morphs. We are unable to confirm the presence of
      consistent karyotypic differences between "Orange with black head" and "Pale
      head, grey nape" specimens, however, P. inframacula, P. textilis, and P. nuchalis
      "Darwin" are found to exhibit distinctive karyotypes, as previously reported.
      These results, in conjunction with additional observations of karyotpic and
      morphological variation, are consistent with nine historically-independent
      lineages (i.e., species) within Pseudonaja. There is strong support for a clade
      composed of P. affinis, P. inframacula, P. ingrami, P. textilis, and the three P.
      nuchalis lineages, and for the relationships (P. inframacula, P. nuchalis
      "Southern") and (P. nuchalis "Darwin", P. nuchalis "Orange with black head"-
      "Pale head, grey nape" ).

PMID- 16098769
TI  - Long term effects on epileptiform activity with vagus nerve stimulation in
      children.
AB  - PURPOSE: We report long-term effects of vagus nerve stimulation (VNS) on
      epileptiform activity in 15 children, and how these changes are related to
      activity stage and to clinical effects on seizure reduction, seizure severity
      (NHS3) and quality of life (QOL). METHODS: Initially, and after 3 and 9 months of
      VNS-treatment, 15 children were investigated with 24 h ambulatory EEG monitoring
      for spike detection. The number of interictal epileptiform discharges (IEDs) and
      the inter spike intervals (ISIs) were analysed during 2 h in the awake state, and
      1h of rapid eye movement (REM)-, spindle- and delta-sleep, respectively. Total
      number and duration of electrographic seizure episodes were also analysed.
      RESULTS: At 9 months the total number of IEDs was significantly reduced (p=0.04).
      There was a tendency of reduction in all activity stages, and significantly so in
      delta-sleep (p=0.008). Total electrographic seizure number was significantly
      reduced in the 24 h EEG at 3 and 9 months (p=0.03, 0.05). There was a significant
      concordance in direction of changes in epileptiform activity and electrographic
      seizures at 9 months (p=0.04). Concordance in direction of changes was seen in 9
      of 15 children between clinical seizures and IED (p>0.3), in 10 of 15 children
      between QOL and IED (p=0.3) and in 8 of 15 children between NHS3 and IED (p>0.3).
      There was no direct correlation between the extent of improvement in these
      clinical data and the degree of spike reduction. CONCLUSION: This study shows
      that VNS reduces IEDs especially in REM and delta sleep, as well as the number of
      electrographic seizures. It also shows a concordance between reduction in IEDs
      and electrographic seizures.

PMID- 16098770
TI  - Validity and reliability of the Italian version of the Quality-of-Life in
      Epilepsy Inventory (QOLIE-31).
AB  - PURPOSE: To develop an Italian adaptation of the shortened version of the Quality
      of-Life in Epilepsy Inventory (QOLIE-31). METHODS: The study population comprised
      503 consecutive ambulatory patients with epilepsy from 44 centers. Internal
      validity was tested by factor analysis, to detect similarities to and differences
      from the original version, and by multitrait/multi-item analysis, to assess item
      convergent and discriminant validity. External validity testing included
      correlation to the SF-36 Inventory, to check the properties of the epilepsy
      specific dimensions. Validity testing was completed by analysis of variance
      (ANOVA) of QOLIE-31 dimension scores against demographic and clinical variables,
      including age, sex, seizure frequency and number of drugs. RESULTS: The domains
      showing the highest internal consistency and the best discriminant validity were
      Medication effect, and Seizure worry. Social functioning had the lower
      discriminant validity. With reference to the SF-36 scores, the study patients
      were slightly but constantly below the population values, mostly for General
      health and Role physical domains. All QOLIE-31 dimensions were sensitive to
      almost any demographic and clinical variable, except for Medication effects
      (sensitive to number of drugs) and Energy-fatigue (sensitive to age).
      CONCLUSIONS: Except for Social functioning, the psychometric properties of the
      Italian adaptation of the QOLIE-31 Inventory are fairly good and similar to the
      American version and the Spanish translation. Social functioning scale suffers
      shortcomings because of life constraints caused by epilepsy (with missing values
      for regular job and driving license).

PMID- 16098771
TI  - Endovascular management of an unusual cause of pancoast syndrome.
AB  - Vascular conditions presenting with Pancoast syndrome are rare. A case of
      vertebral artery pseudoaneurysm presenting with Pancoast syndrome is reported.
      The aneurysm was successfully treated by proximal coil embolization.

PMID- 16098772
TI  - Shoab and Aly on Campbell et al.

PMID- 16098773
TI  - Strategies for abdominal aortic aneurysms-a pendulum in forward motion.

PMID- 16098774
TI  - Outcome after occlusion of infrainguinal bypasses in the Dutch BOA Study:
      comparison of amputation rate in venous and prosthetic grafts.
AB  - OBJECTIVE: To compare the consequences of occlusion of infrainguinal venous and
      prosthetic grafts. METHODS: In total, 2690 patients were included in the Dutch
      BOA study, a multicenter randomised trial that compared the effectiveness of oral
      anticoagulants with aspirin in the prevention of infrainguinal bypass graft
      occlusion. Two thousand four hundred and four patients received a femoropopliteal
      or femorodistal bypass with a venous (64%) or prosthetic (36%) graft. The
      incidence of occlusion and amputation was calculated according to graft material
      and the incidence of amputation after occlusion was compared with Cox regression
      to adjust for differences in prognostic factors. RESULTS: The indication for
      operation was claudication in 51%, rest pain in 20% and tissue loss in 28% of
      patients. The mean follow up was 21 months. After venous bypass grafting 171
      (15%) femoropopliteal and 96 (24%) femorodistal grafts occluded. After prosthetic
      bypass grafting 234 (30%) femoropopliteal and 25 (38%) femorodistal grafts
      occluded. Patients with occlusions in the venous group had more severe ischemia,
      less runoff vessels and were older than the patients with prosthetic grafts. In
      the venous occlusion group 54 (20%) amputations were performed compared to 42
      (16%) in the prosthetic occlusion group; crude hazard ratio 1.17 (95% CI 0.78
      1.75). After adjustment for above mentioned differences in patient
      characteristics the hazard ratio was 0.86 (95% CI 0.56-1.32). CONCLUSION: The
      need for amputation after occlusion is not influenced by graft material in
      infrainguinal bypass surgery.

PMID- 16098775
TI  - Fourier transform infrared microscopy and imaging: detection of fungi in wood.
AB  - FTIR microscopy was used to detect and discriminate the two wood decaying fungi
      Trametes versicolor and Schizophyllum commune in experimentally infected beech
      wood blocks. The distribution of fungal mycelium in wood was locally resolved and
      semiquantitatively recorded using FTIR microscopy combined with a focal plane
      array detector and image analysis. Cluster analysis revealed major differences
      between FTIR spectra recorded from wood fibers and empty vessel lumina and
      spectra from mycelium of both fungal species, irrespective of whether the fungi
      were grown on the surface of wood or inside vessel lumina. Species-specific
      clustering of spectra of fungal mycelium grown on the wood surface and inside
      vessel lumina demonstrated the potential of FTIR microscopy to discriminate among
      fungal species decaying wood.

PMID- 16098776
TI  - Aspergillus nidulans swoK encodes an RNA binding protein that is important for
      cell polarity.
AB  - The Aspergillus nidulans swoK1 mutant is defective in polarity maintenance when
      grown at restrictive temperature (38 degrees C). Upon germination, the mutant
      extends a primary germ tube that swells to an enlarged, non-uniform cell with
      pronounced wall thickenings. The mutant is fully restored to wild-type growth
      when transformed with a plasmid containing the AN5802.2 ORF as designated in The
      Broad Institute A. nidulans sequence database. Genetic mapping places swoK in the
      same region of chromosome I, as that occupied by An5802.2 on the physical map.
      swoK is predicted to encode a protein that contains an N-terminal RRM (RNA
      Recognition Motif) and a highly repetitive C-terminus with numerous RD/DR and
      RS/SR dipeptides. We hypothesize that SwoK participates in one of the known
      functions of SR proteins (those that contain SR/RS repeats): mRNA maturation
      through the spliceosome and or transport of mRNAs out of the nucleus to sites of
      protein translation.

PMID- 16098777
TI  - Decreased sensitivity to experimental pain in adjustment disorder.
AB  - An altered perception of pain has been described for several psychiatric
      disorders. To date the influence of adjustment disorders (AD) on pain perception
      has not been described. Here, we investigated perception of experimentally
      induced pain in 15 patients suffering from AD (subtype with depressive symptoms)
      and controls matched for age and sex. Thresholds and tolerances were assessed for
      thermal and electrical pain on both sides of the body. We found an overall
      increase of pain thresholds and tolerances in AD patients as compared to
      controls, predominately on the right side of the body. Analogue findings have
      been reported for pain perception in major depressive disorder (MDD). Of the data
      obtained, only thermal pain threshold on the right arm correlated with the
      severity of depressive symptoms. Although the underlying pathology is elusive it
      is likely that the mechanisms for reduced pain sensitivity are comparable in MDD
      and AD.

PMID- 16098778
TI  - Acquisition time reduction in magnetic resonance spectroscopic imaging using
      discrete wavelet encoding.
AB  - This paper describes a new magnetic resonance spectroscopic imaging (MRSI)
      technique based upon the discrete wavelet transform to reduce acquisition time
      and cross voxel contamination. Prototype functions called wavelets are used in
      wavelet encoding to localize defined regions in localized space by dilations and
      translations. Wavelet encoding in MRSI is achieved by matching the slice
      selective RF pulse profiles to a set of dilated and translated wavelets. Single
      and dual band slice selective excitation and refocusing pulses, with profiles
      resembling Haar wavelets, are used in a spin-echo sequence to acquire 2D-MRSI
      wavelet encoding data. The 2D space region is spanned up to the desired
      resolution by a proportional number of dilations (increases in the localization
      gradients) and translations (frequency shift) of the Haar wavelets (RF pulses).
      Acquisition time is reduced by acquiring successive MR signals from regions of
      space with variable size and different locations with no requirement for a TR
      waiting time between acquisitions. An inverse wavelet transform is performed on
      the data to produce the correct spatial MR signal distribution.

PMID- 16098779
TI  - Scoring binding affinity of multiple ligands using implicit solvent and a single
      molecular dynamics trajectory: application to influenza neuraminidase.
AB  - We explore a perturbative approach to calculation of binding free energy of
      multiple ligands, based on a single molecular dynamics simulation of a reference
      ligand-receptor complex and analysis via a hybrid force field/continuum model
      potential. The methodology is applied to prediction of relative binding free
      energies of 10 Influenza neuraminidase inhibitors, using Poisson-Boltzmann and
      generalised Born models of implicit solvent. These single-step MM-PB/SA and MM
      GB/SA approaches predict the experimentally most potent ligand as first- or
      second-ranked according to total binding free energy. Ranking of inhibitors
      displays only moderate sensitivity to the choice of reference trajectory and
      ligand partial charge scheme. When ranked according to total electrostatic
      binding free energy, correlation with experiment improves (r(2) of 0.72); this
      may be related to underestimated first solvation shell effects by the implicit
      water models. Therefore, to increase the generality of this single-step approach
      as part of a potential computational compound optimisation strategy, further
      development of the treatment of short-range solvent interactions is warranted.

PMID- 16098780
TI  - Effects of nitric oxide in 5-hydroxytryptamine-, cholera toxin-, enterotoxigenic
      Escherichia coli- and Salmonella Typhimurium-induced secretion in the porcine
      small intestine.
AB  - The effects of nitric oxide (NO) in the secretory response to the endogenous
      secretagogue 5-hydroxytryptamine (5-HT), the enterotoxins heat-labile
      enterotoxigenic Escherichia coli (ETEC) toxin (LT) and cholera toxin (CT), and
      various cultures of ETEC and Salmonella serotype Typhimurium in the porcine small
      intestine (Sus scrofa) were investigated. In anaesthetized pigs, jejunal tied-off
      loops were instilled with 5-HT, LT, CT, various cultures of ETEC or S.
      Typhimurium. Pigs were given intravenously isotonic saline or isotonic saline
      containing the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L
      NAME). L-NAME significantly induced an increased fluid accumulation in loops
      induced by 5-HT, ETEC and stn-mutated S. Typhimurium. Fluid accumulation in loops
      instilled with wild-type S. Typhimurium was increased by L-NAME, although not
      significantly, while there was no effect on fluid accumulation induced by an invH
      mutated isogenic strain. No significant effect of L-NAME was observed on the
      fluid accumulation induced by the purified enterotoxins LT and CT. The results
      also demonstrated a relatively large difference in the ability to induce fluid
      accumulation between the bacteria strains. Diastolic, systolic and mean blood
      pressures were significantly increased and the body temperature was significantly
      decreased in groups of pigs treated with L-NAME. In conclusion, the results
      suggest that NO has a proabsorptive effect in the intact porcine jejunum and is
      involved in the systemic vascular tone.

PMID- 16098781
TI  - Expression of insulin-like growth factor-I and insulin-like growth factor binding
      proteins during thioacetamide-induced liver cirrhosis in rats.
AB  - OBJECTIVE: The liver plays a central role in insulin-like growth factor (IGF)
      homeostasis providing the majority of circulating IGF-I and some of its binding
      proteins (IGFBPs). In liver cirrhosis the IGF axis is severely disturbed, and
      these alterations are associated with reduced IGF-I, IGFBP-3 but elevated IGFBP-1
      serum levels. METHODS: By Northern blotting and in situ hybridization (ISH),
      hepatic expression of IGF-I and of IGFBP was studied in a rat model of liver
      cirrhosis induced by thioacetamide. RESULTS: ISH revealed a homogeneous
      distribution of IGFBP-1, IGFBP-4 and IGF-I mRNA over hepatic parenchyma in normal
      and cirrhotic liver. Fibrous septa of cirrhotic liver were IGFBP-1 mRNA negative,
      whereas IGFBP-4 and IGF-I transcripts were detected in single cells. In normal
      liver, IGFBP-3 mRNA was distributed within nonparenchymal cells of the hepatic
      lobule and in the wall of the portal vein. In cirrhotic liver, IGFBP-3
      transcripts were abundant in mesenchymal cells of fibrous tissue. IGFBP-3 mRNA
      expression was also prominent in cells at the septal-nodular interface most
      likely representing monocyte infiltration. IGFBP-3 mRNA expression was reduced in
      nonparenchymal liver cells located more distantly from the septal-nodular
      interface in the cirrhotic nodule that correlated with reduced IGFBP-3 mRNA
      expression observed in Kupffer cells (KC) and sinusoidal endothelial cells (SEC)
      isolated from macronodular cirrhotic livers. CONCLUSION: Cirrhosis is accompanied
      by an altered spatial expression of IGFBP-3 in liver tissue, which is
      characterized by decreased levels of IGFBP-3 mRNA in KC and SEC, but elevated
      IGFBP-3 expression in myofibroblast-like cells and inflammatory infiltrate.

PMID- 16098782
TI  - Model of central and trimethylammonium metabolism for optimizing L-carnitine
      production by E. coli.
AB  - The application of metabolic engineering principles to the rational design of
      microbial production processes crucially depends on the ability to make
      quantitative descriptions of the systemic ability of the central carbon
      metabolism to redirect fluxes to the product-forming pathways. The aim of this
      work was to further our understanding of the steps controlling the
      biotransformation of trimethylammonium compounds into L-carnitine by Escherichia
      coli. Despite the importance of L-carnitine production processes, development of
      a model of the central carbon metabolism linked to the secondary carnitine
      metabolism of E. coli has been severely hampered by the lack of stoichiometric
      information on the metabolic reactions taking place in the carnitine metabolism.
      Here we present the design and experimental validation of a model which, for the
      first time, links the carnitine metabolism with the reactions of glycolysis, the
      tricarboxylic acid cycle and the pentose-phosphate pathway. The results
      demonstrate a need for a high production rate of ATP to be devoted to the
      biotransformation process. The results demonstrate that ATP is used up in a
      futile cycle, since both trimethylammonium compound carriers CaiT and ProU
      operate simultaneously. To improve the biotransformation process, resting
      processes as well as CaiT or ProU knock out mutants would yield a more efficient
      system for producing L-carnitine from crotonobetaine or D-carnitine.

PMID- 16098783
TI  - Chromomycosis: a new Tunisian case report.

PMID- 16098784
TI  - Involvement of protein kinase C in the inhibition of lipopolysaccharide-induced
      nitric oxide production by thapsigargin in RAW 264.7 macrophages.
AB  - This study explored the effects of inhibition of endoplasmic reticulum (ER)
      Ca(2+)-ATPase on lipopolysaccharide (LPS)-induced protein kinase C (PKC)
      activation, nuclear factor-kappaB (NF-kappaB) translocation, inducible nitric
      oxide synthase (iNOS) expression and nitric oxide (NO) production in RAW 264.7
      macrophages. Thapsigargin (TG) irreversibly inhibits ER Ca(2+)-ATPase and LPS
      induced NO production is reduced even after washout. TG also attenuated LPS
      stimulated iNOS expression by using immunoblot analysis. However, another
      distinct fully reversible ER Ca(2+)-ATPase inhibitor, 2,5-di-tert
      butylhydroquinone (DBHQ), ionophore A23187 and ionomycin could exert a similar
      effect to TG in increasing intracellular calcium concentration; however, these
      agents could not mimic TG in reducing iNOS expression and NO production. LPS
      increased PKC-alpha and -beta activation, and TG pretreatment attenuated LPS
      stimulated PKC activation. Not did pretreatment with DBHQ, A23187 and ionomycin
      reduce LPS-stimulated PKC activation. Furthermore, NF-kappaB-specific DNA-protein
      binding activity in the nuclear extracts was enhanced by treatment with LPS, and
      TG pretreatment attenuated LPS-stimulated NF-kappaB activation. None of DBHQ,
      A23187 and ionomycin pretreatment reduced LPS-stimulated NF-kappaB activation.
      These data suggest that persistent inhibition of ER Ca(2+)-ATPase by TG would
      influence calcium release from ER Ca2+ pools that was stimulated by the LPS
      activated signal processes, and might be the main mechanism for attenuating PKC
      and NF-kappaB activation that induces iNOS expression and NO production.

PMID- 16098785
TI  - Opportunistic emissions of volatile isoprenoids.
AB  - Isoprene, monoterpenes and sesquiterpenes are synthesized and emitted by some
      plant species, but not all plant species have this ability. These volatile,
      nonessential isoprenoid compounds share the same biochemical precursors as larger
      essential isoprenoids such as gibberellic acids and carotenoids. They have many
      protective and ecological functions for the plant species that produce them, but
      plant species that do not produce these compounds also grow and reproduce
      successfully. Here, we develop an 'opportunist hypothesis' suggesting that (i)
      volatile isoprenoid production takes advantage of dimethylallyl diphosphate
      (DMAPP) and its isomer isopentenyl diphosphate (IPP), which are synthesized
      primarily to produce essential isoprenoids, and (ii) conditions affecting
      synthesis of the higher isoprenoids will affect the production and emission of
      volatile isoprenoids.

PMID- 16098786
TI  - Recently approved and investigational antibiotics for treatment of severe
      infections caused by Gram-positive bacteria.
AB  - The development of resistance in the major pathogenic Gram-positive genera
      Staphylococcus and Streptococccus has led to the need for new agents that are
      able to overcome existing resistance mechanisms or that have novel mechanisms of
      action. There is currently a dearth of new agents that are active against
      resistant bacterial species. Agents that have recently been approved for clinical
      use include linezolid, the first oxazolidinone in clinical use, daptomycin, the
      first lipopeptide in clinical use, and telithromycin, a ketolide that is derived
      from clarithromycin. Agents currently in clinical development include
      tigecycline, a broad-spectrum intravenous tetracycline, ceftobiprole, a broad
      spectrum cephalosporin that has activity against methicillin-resistant
      staphylococci, DX-619 and WCK-771, which are potent quinolones that have activity
      against quinolone-resistant staphylococci, oritavancin and dalbavancin, both of
      which are new glycopeptides, and iclaprim, which is a diaminopyrimidine.
      Additional agents that are in preclinical development against Gram-positive
      pathogens include quinoline-naphthyridine agents, which target novel DNA gyrase
      sites, other novel quinolones that have high potency, peptide deformylase
      inhibitors, and new lincosamide, oxazolidinone, lipopeptide and cephalosporin
      derivatives. Misuse of potent new agents will, however, result in the inevitable
      development of resistance to these agents; responsible use of potent new agents
      is required to prevent continuation of this vicious cycle.

PMID- 16098787
TI  - Point-of-care molecular diagnostic systems--past, present and future.
AB  - The field of molecular diagnostics has greatly decreased the time it takes to
      identify infectious agents and to test their antimicrobial resistance. Portable
      devices are currently in development that can easily identify a variety of
      nucleic acid targets (either DNA or RNA) from multiple sample types in under an
      hour. This is done by a variety of methods including real-time polymerase chain
      reaction, probe-based assays, bioluminescence real-time amplification, and
      microarray or micro-pump technologies. These self-contained systems require only
      minimal training and perform all steps of the assay from extraction through
      detection with little or no operator intervention.

PMID- 16098788
TI  - Crystal field analysis of energy level structure of LiAlO2:V3+ and LiGaO2:V3+.
AB  - A detailed analysis of the energy level structure of tetrahedrally coordinated
      V(3+) ion in lithium aluminum oxide LiAlO(2) (gamma-phase) and lithium
      dioxogallate LiGaO(2) is performed using the exchange charge model of the crystal
      field theory. The parameters of the crystal field acting on the V(3+) optical
      electrons are calculated from crystal structure data assuming C(1) point symmetry
      of the [VO(4)](5-) impurity center in LiAlO(2) and LiGaO(2). Crystal field
      splitting of all five LS terms of the V(3+) ion ((3)F, (3)P, (1)S, (1)D, (1)G) is
      calculated. The energy levels obtained are compared with experimental absorption
      spectra and results of application of other crystal field models (the angular
      overlap model and Racah theory) to the considered crystals; though only one
      fitting parameter of the exchange charge model was used, a good agreement with
      experimental data on the ground and excited state absorption is demonstrated.

PMID- 16098789
TI  - Synthesis, characterization and semi-empirical calculations for the thiocyanate
      linkage isomers of an (alpha-iminooxime)cobalt(III) macrocyclic complex.
AB  - Herein we report the synthetic route and detailed characterization of the
      macrocyclic complex [Co(dohpn)(SCN)2] and its linkage isomer (dohpn=2,3,9,10
      tetramethyl-1,4,8,11-tetraazaundecane-1,3,8,10-tetraen-11-ol-1-olate and
      py=pyridine) based on analytical, spectroscopic and electrochemical methods.
      Structural, vibrational and electronic features are discussed and a coherent
      assignment is proposed on the basis of semi-empirical theoretical calculations.

PMID- 16098790
TI  - Experimental (FT-IR, FT-Raman, 1H NMR) and theoretical study of magnesium,
      calcium, strontium, and barium picolinates.
AB  - The experimental IR, Raman, and 1H NMR spectra of picolinic acid, as well as
      magnesium, calcium, strontium, and barium picolinates were registered, assigned
      and studied. Characteristic changes in the spectra of metal picolinates in
      comparison with the spectrum of ligand were observed, which lead to the
      conclusion that perturbation of the aromatic system of picolinates increases
      along with the series Mg-->Ca-->Sr-->Ba. Theoretical structures of beryllium and
      magnesium picolinates, as well as theoretical IR spectrum of magnesium picolinate
      were calculated in B3PW91/6-311++G(d, p) level. On the basis of calculated bond
      lengths in pyridine ring geometric, aromaticity indexes HOMA were calculated. The
      idea of these indexes is based on the fact that the essential factor in aromatic
      stabilization is the pi delocalization manifested in: planar geometry,
      equalization of the bond lengths and angles, and symmetry. The decidedly lower
      value of HOMA for magnesium picolinate (i.e. 0.545; 0.539) than that for
      beryllium picolinate (i.e. 0.998; 0.998) indicate higher aromatic properties of
      Be picolinate than of Mg picolinate. The comparison of theoretical and literature
      experimental structures of magnesium picolinate was done. The experimental
      structure contains two water molecules, so the calculations for hydrated
      magnesium picolinate were carried on, and the influence of coordinated water
      molecule on the structure of picolinates was discussed. The HOMAs for hydrated
      experimental and calculated Mg picolinate amount to 0.870; 0.743, and 0.900;
      0.890, respectively, whereas for anhydrous structure, it is as described above,
      i.e. 0.545; 0.539. Thus, the calculations clearly showed that water molecules
      coordinated to the central atom weakens the effect of metal on the electronic
      system of ligand.

PMID- 16098791
TI  - Low frequency internal modes of 1,2,4,5-tetramethylbenzene, tetramethylpyrazine
      and tetramethyl-1,4-benzoquinone INS, Raman, infrared and theoretical DFT
      studies.
AB  - The results of inelastic neutron scattering (INS), Raman and infrared (IR)
      studies on 1,2,4,5-tetramethylbenzene (durene), tetramethylpyrazine (TMP) and
      tetramethyl-1,4-benzoquinone (TMBQ) in the solid state are reported. The observed
      frequencies are analyzed on the basis of DFT calculations. The low frequency
      region, below 400 cm(-1), related to the torsional and bending out-of-plane
      vibrations of the CH(3) groups, is of particular interest. The detailed analysis
      is possible due to the simulation of the INS spectra by using the auntie-CLIMAX
      program. It is shown that the observed low frequency INS bands are dramatically
      shifted, compared to the calculated ones, towards higher frequencies. Although
      one cannot exclude deficiencies of theoretical methods as applied to low
      frequency modes, it seems more probable the interpretation based on an existence
      of non-conventional CH(...)pi, CH(...)N, CH(...)O hydrogen bonds formed by the
      methyl groups in crystalline phases.

PMID- 16098792
TI  - Structural and spectroscopic studies on some chloropyrimidine derivatives by
      experimental and quantum chemical methods.
AB  - Ab initio quantum chemical and experimental spectroscopic studies in the infrared
      (4000-60 cm(-1)) and UV spectral regions are being reported on 4-chloro-2,6
      dimethylsulfanyl pyrimidine-5-carbonitrile and 4-chloro-2-methylsulfanyl-6-(2
      thienyl) pyrimidine-5-carbonitrile. Optimized geometries, electronic charge
      distribution, dipole moments and three-dimensional molecular electrostatic
      potential surfaces have been obtained. These have been used to understand the
      structure and spectral characteristics of the two compounds. A complete
      assignment of vibrational spectra on the basis of DFT/6-311G** and electronic
      spectra on the basis of TD-DFT/6-31+G* 5D calculations have been attempted for
      the two molecules.

PMID- 16098793
TI  - Molecular structure, IR and Raman spectra as well as DFT chemical calculations
      for alkylaminoacetylureas: vibrational characteristics of dicarbonylimide bridge.
AB  - The present work reports room temperature IR and Raman study of R-NH-CH2-CO-NH-CO
      NH2 alkylaminoacetylureas (R=C3H7, C4H9, C5H11, C6H13, C7H15, C8H17, C9H19,
      C10H21, C12H25, C14H29, C16H33 and C18H37). The experimental energy levels have
      been compared to those obtained from DFT chemical quantum calculations performed
      with the use of B3LYP/6-31G (d,p) basis for the R=C3H7 derivative. Energies of 66
      vibrational states have been calculated for this molecule. Its molecular symmetry
      was taken as C1 and was optimized in the both quantum models applied. The role of
      the hydrogen bond in the stabilization of the structure has been analyzed.

PMID- 16098794
TI  - Molecular adducts between a few phenolic donors and pi-acceptors in solid-state.
AB  - Electron donor-acceptor molecular complexes of a few phenolic donors with some
      quinonoid and tetracyanoethylene acceptors have been prepared by two different
      methods, i.e., by simple grinding of the respective component pair in the solid
      state and in solution. Both the methods yielded identical dark colored 1:1
      stoichiometric complexes. Spectral studies revealed that the complexes are ionic
      in nature. The g values obtained in ESR spectral studies for all these molecular
      adducts vary between 2.000 and 2.022, confirming the free radical nature of the
      adducts. The electronic absorption spectral studies proved that the donor
      acceptor complexes formed initially, exhibit new electronic transitions at longer
      wavelengths, are less stable and disassociate readily into ionic type of adducts.
      The absorption maximum at longer wavelengths, i.e. >or=550 nm, are assigned to
      the charge transfer complexes, while the new transition at around 410 +/- 5 nm is
      attributed to the anion radical of the adducts. The ease of complexation not only
      depends on the ionization potential and electron affinities of the phenolic
      donors and the acceptors but is also structure sensitive. Complexation is
      confirmed by the shift in IR absorption of the phenolic hydroxyl group and the
      carbonyl group of quinone acceptors and the cyano group of tetracyanoethylene.
      Proton magnetic resonance studies indicate an interaction between the phenolic
      donors and acceptors on basis of the altered chemical shifts. Further, IR and NMR
      studies show that the stability of the adducts is governed not only by the charge
      transfer interaction but also by hydrogen bonding.

PMID- 16098795
TI  - The influence of planarity, rigidity and internal heavy atom upon fluorescence
      parameters and the intersystem crossing rate constant in molecules with the
      biphenyl basis.
AB  - Fluorescence properties of 10 specially chosen aromatic compounds with the
      biphenyl basis, differing in the degree of planarity, rigidity and in the nature
      of the internal heavy atom, but family-related in pi-structure are experimentally
      studied at room temperature (293K). The quantum yield of fluorescence, gamma, and
      fluorescence decay time, pi(f), of deaerated and non-deaerated cyclohexane
      solutions are measured. The oscillator strength, f(e), of S0-->S1 transition,
      fluorescence rate constant, k(f), natural lifetime, tau0(T), and intersystem
      crossing rate constant, k(ST), are calculated for each compound. It was observed
      that the increase in planarity and rigidity causes the k(ST) value to decrease
      very significantly. Any disturbance of the pi-system by the torsional vibrations
      of the substituted part of the molecule causes the k(ST) value to increase. The
      introduction of a heavy atom instead of the methylene bridge of fluorene leads to
      the increase in the k(ST) value and to the decrease in the f(e) of the 1A-->1La
      transition. The absence of laser action of fluorene is explained.

PMID- 16098796
TI  - Structural characterization of tellurite glasses doped with transition metal
      oxides using Raman spectra and ab initio calculations.
AB  - Systems of iron tellurite glasses were prepared by melt quenching with
      compositions of [85%TeO2+5%Fe2O3+10%TMO], where transition metal oxides (TMO) are
      TiO2, V2O5, MnO, CoO, NiO and CuO. Furthermore, the main structural units of
      these samples have been characterized by means of Raman spectra (150-1200 cm(-1))
      as well as wavenumber predictions by means of Gaussian 98 ab initio calculations
      for the proposed site symmetries of TeO4(4-) triagonal bipyramid (C2v) and
      Te2O7(6-) bridged tetrahedra (Cs and C1). Aided by normal coordinate analysis,
      calculated vibrational frequencies, Raman scattering activities, force constants
      in internal coordinates and potential energy distributions (PEDs), revised
      vibrational assignments for the fundamental modes have been proposed. The main
      structural features are correlated to the dominant units of triagonal bipyramid
      (tbp) or bridged tetrahedral (TeO3+1 binds to TeO3 through TeOTe bridge; corner
      sharing). Moreover, the Raman spectra of the investigated tellurites reflect a
      structural change from tbp (coordination number is four) to triagonal pyramidal
      (coordination number is three).

PMID- 16098797
TI  - Infrared study of the acidic and basic forms of betaxolol.
AB  - Betaxolol and its respective hydrochloride salt were studied in solution by
      computational calculations and infrared spectroscopy. The solution molecular
      conformations were taken to be the same as those exhibited by the compounds in
      the solid state given by X-ray diffraction and calculated after full geometry
      optimization by ab initio Hartree-Fock methods using the 6-31G(d) basis set.
      Infrared spectra of carbon tetrachloride solutions provide valuable information
      on the structure of the compounds in non-polar solvents at different
      concentrations.

PMID- 16098800
TI  - Manganese(II) complexes of substituted di-2-pyridyl ketone thiosemicarbazones:
      structural and spectral studies.
AB  - The reaction between manganese(II) acetate and two substituted thiosemicarbazones
      derived from di-2-pyridyl ketone (HL) in 1:2 molar ratio produces new complexes
      of general formula [MnL2]. The thiosemicarbazone moiety in HL deprotonates and
      gets coordinated to Mn(II) through the azomethine nitrogen, one of the pyridyl
      nitrogens, and the thiolate sulfur in both the complexes. The crystal structure
      of [MnL2(1)] was established by single crystal X-ray diffraction and the compound
      crystallizes into a monoclinic lattice with P2(1)/c space group. Manganese(II)
      exists in a distorted octahedral geometry in the complexes.

PMID- 16098799
TI  - Novel copper(II) homobinuclear macrocyclic complexes: cyclic voltammetry,
      biological properties and spectral studies.
AB  - A series of five new copper(II) macrocyclic complexes have been synthesized by
      template condensation. The bonding and stereochemistry of the complexes have been
      characterized by elemental analysis, molar conductance, magnetic susceptibility,
      IR, UV-visible, EPR spectral studies and electrochemical properties. g-Values are
      calculated for all of the complexes in polycrystalline form as well as in DMSO
      solution. The magnetic and spectral data indicate square planar geometry for all
      the complexes. Cyclic voltammograms for all the complexes are similar and involve
      two quasi-reversible redox processes. Cu(II)Cu(II)<=>Cu(II)Cu(I)<=>Cu(I)Cu(I).
      Their biological properties have also been studied. The macrocyclic complexes
      show more anti-bacterial than controlled one. The anti-bacterial activities of
      the compounds were tested against Streptococcus fecalis and Escherichia coli with
      different concentrations.

PMID- 16098798
TI  - Electrochemiluminescence of terbium (III)-two fluoroquinolones-sodium sulfite
      system in aqueous solution.
AB  - The electrochemiluminescence (ECL) of Tb3+-enoxacin-Na2SO3 system (ENX system)
      and Tb3+-ofloxacin-Na2SO3 system (OFLX system) in aqueous solution is reported.
      ECL is generated by the oxidation of Na2SO3, which is enhanced by Tb3+
      fluoroquinolone (FQ) complex. The ECL intensity peak versus potential corresponds
      to oxidation of Na2SO3, and the ECL emission spectra (the peaks are at 490, 545,
      585 and 620 nm) match the characteristic emission spectrum of Tb3+, indicating
      that the emission is from the excited state of Tb3+. The mechanism of ECL is
      proposed and the difference of ECL intensity between ENX system and OFLX system
      is explained. Conditions for ECL emission were optimized. The linear range of ECL
      intensity versus concentrations of pharmaceuticals is 2.0 x 10(-10) -8.0 x 10(
      7)mol l(-1) for ENX and 6.0 x 10(-10) -6.0 x 10(-7)mol l(-1) for OFLX,
      respectively. A theoretical limit of detection is 5.4 x 10(-11)mol l(-1) for ENX
      and 1.6 x 10(-10)mol l(-1) for OFLX, respectively. The ECL was satisfactorily
      applied to the determination of the two FQs in dosage form and urine sample.

PMID- 16098801
TI  - Investigation on the interactions between diperoxovanadate and substituted
      phenanthroline.
AB  - Detailed investigations were carried out to explore the interaction systems of
      NH4VO3/H2O2/5,6-dimethyl-1,10-phenanthroline and NH4VO3/H2O2/5-methyl-1,10
      phenanthroline in aqueous solution under physiological conditions by NMR
      spectroscopy, such as 1D 1H, 13C, 51V variable temperature, and 2D COSY, NOESY,
      HETCOR, COLOC techniques as well as density functional calculations. New species
      [OV(O2)2(5,6-dimethyl-1,10-phenanthroline)]- and [OV(O2)2(5-methyl-1,10
      phenanthroline)]- including isomers were formed in a bidentate coordination
      fashion which were stable under the experimental conditions. The solution
      structures of these new species were proposed based on the direct NMR
      experimental information and confirmed by the theoretical calculations. All the
      1H and 13C NMR peaks were assigned. The calculated 1H and 13C chemical shifts on
      the whole are in fair agreement with the experimental values. The methyl groups
      on the aromatic ring of the three new complexes were found to have a steric
      hindrance effect on the coordination process. Experimental results show that the
      order of coordination capability of phenanthroline and its derivants was: 1,10
      phenanthroline>5-methyl-1,10-phenanthroline>5,6-dimethyl-1,10-phenanthroline.

PMID- 16098802
TI  - Spectral characteristics and nonlinear studies of crystal violet dye.
AB  - Solid-state dye-doped polymer is an attractive alternative to the conventional
      liquid dye solution. In this paper, the spectral characteristics and the
      nonlinear optical properties of the dye crystal violet are studied. The spectral
      characteristics of crystal violet dye doped poly(methylmethacrylate) modified
      with additive n-butyl acetate (nBA) are studied by recording its absorption and
      fluorescence spectra and the results are compared with the corresponding liquid
      mixture. The nonlinear refractive index of the dye in nBA and dye doped polymer
      film were measured using z-scan technique, by exciting with He-Ne laser. The
      results obtained are intercompared. Both the samples of dye crystal violet show a
      negative nonlinear refractive index. The origin of optical nonlinearity in the
      dye may be attributed due to laser-heating induced nonlinear effect.

PMID- 16098803
TI  - Preparation and characterization of inclusion complexes of pefloxacin mesylate
      with three kinds of cyclodextrins.
AB  - The ability of alpha-cyclodextrin, beta-cyclodextrin and hydroxypropyl-beta
      cyclodextrin (alpha-CD, beta-CD and HP-beta-CD) to break pefloxacin mesylate (PM)
      aggregates by forming inclusion complexes has been studied using 1H NMR (nuclear
      magnetic resonance spectroscopy), 13C NMR and fluorescence spectra. The inclusion
      constants are determined to compare the corresponding inclusion capacity. Solid
      inclusion complexes of PM with CDs are synthesized by coprecipitation method, and
      all the inclusion ratios are found to be 1:1. Additionally, spatial
      characterization of complexes has been proposed based on two-dimensional nuclear
      magnetic resonance technique (2D NMR) and spatial conformation is also
      investigated to propose two possible models between PM and CDs.

PMID- 16098804
TI  - Synthesis, spectral and thermal studies of some organotin(IV) derivatives of 5
      amino-3H-1,3,4-thiadiazole-2-thione.
AB  - Some tri- and diorganotin(IV) compounds of the general formula, RnSnL4-n (where
      n=2, R=Me, n-Bu and Ph; n=3, R=Me, n-Bu, n-Pr and Ph; HL=5-amino-3H-1,3,4
      thiadiazole-2-thione) have been synthesized by the reaction of RnSnCl4-n (where
      n=2 or 3, R=Me, n-Bu, n-Pr and Ph) and the sodium salt of the ligand. Oct2SnL2
      was obtained by the reaction of Oct2SnO with HL in a 1:2 molar ratio under
      azeotropic removal of water. The bonding and coordination behavior in these
      derivatives are discussed on the basis of IR, Far-IR, multinuclear (1H, 13C and
      119Sn) NMR and 119Sn Mossbauer spectroscopic studies. These investigations
      suggest that in all the compounds the ligand acts as monoanionic bidentate
      coordinating through ring N(3) and exocyclic S. Thermal studies of five
      compounds, viz., Ph3SnL, Me2SnL2, n-Bu2SnL2, Oct2SnL2 and Ph2SnL2 have been
      carried out in the temperature range 25-1000 degrees C using TG, DTG and DTA
      techniques under an atmosphere of dry nitrogen.

PMID- 16098805
TI  - Electronic structure of orotic acid III geometric feature and thermal properties
      of some transition metal orotic acid complexes.
AB  - The complexes of orotic acid with Co(II), Ni(II), Fe(III), Cu(II), and Cd(II)
      were prepared and their stoichiometry were determined by elemental analysis.
      Co(II) and Ni(II) give complexes with orotic acid of 1:1 ratio whereas that of
      the remaining transition metals give complexes of 1:2 ratio. The stereochemistry
      of the studied metal complexes has been established by analyses of their
      electronic spectra and magnetic susceptibilities. The mode of bonding in the
      studied series of metal complexes was established via, analysis of their infrared
      spectra. The present analysis leads to the conclusion that all metal ions studied
      coordinate to orotic acid via N(1) and the adjacent carboxylate group. Thermal
      decomposition studies of orotic acid complexes have been carried out as to
      understand the status of water molecules present in these complexes as well as to
      know their general decomposition pattern. Theoretical investigation of the
      electronic structure of the studied metal complexes has been carried out. MO
      computations at the HF-level were performed. Charge density distribution, extent
      of distortion from regular geometry, dipole moment, and orientation were computed
      and discussed.

PMID- 16098809
TI  - Pyrimidine pathways in health and disease.
AB  - Genetic defects involving enzymes essential for pyrimidine nucleotide metabolism
      have provided new insights into the vital physiological functions of these
      molecules in addition to nucleic acid synthesis. Such aberrations disrupt the
      haematological, nervous or mitochondrial systems and can cause adverse reactions
      to analogue therapy. Regulation of pyrimidine pathways is also known to be
      disrupted in malignancies. Nine genetic defects have now been identified but only
      one is currently treatable. Diagnosis is aided by the accumulation of specific
      metabolites. Recently, progress has been made in understanding the molecular
      mechanisms underlying inborn errors of pyrimidine metabolism, together with the
      key clinical issues and the implications for the future development of novel
      drugs and therapeutic strategies.

PMID- 16098808
TI  - Symptoms of thoracic outlet syndrome in women with carpal tunnel syndrome.
AB  - OBJECTIVE: To evaluate the frequency of symptoms and signs suggestive of thoracic
      outlet syndrome (TOS) in women aged 60 years or less, with unambiguous carpal
      tunnel syndrome (CTS). METHODS: The CTS was clinically and electrodiagnostically
      defined in 100 upper limbs. Clinical and electrophysiological symptoms and signs
      suggestive of TOS, true neurogenic TOS (NTOS) and disputed NTOS were tested in
      each upper limb. The 100 idiopathic median nerve lesions at the wrist occurred in
      61 successive and unselected women. Women with ulnar nerve entrapment, root
      lesions and polyneuropathies were excluded. The main outcome measures were
      clinical symptoms and signs suggestive of TOS and NTOS as electrodiagnostic
      evaluation of the lower brachial plexus. RESULTS: In the 100 upper limbs with
      definite CTS, no major symptoms and signs suggestive of TOS and NTOS were found.
      On the contrary, moderate and mild clinical symptoms and signs suggestive of
      disputed NTOS were frequently found, even if no electrodiagnostically definite
      major or minor lower brachial plexus lesion was found. CONCLUSIONS: This study
      demonstrates the low specificity of clinical symptoms and signs suggestive of
      disputed NTOS, as they were frequently found in women with unselected and
      unambiguous CTS, despite no patients had definite lower brachial plexus lesion.
      SIGNIFICANCE: Our study shows why CTS can easily be misdiagnosed as disputed
      NTOS, and stresses the importance of systematic electrodiagnosis with median,
      ulnar, and medial antebrachial cutaneous nerve conduction studies, in order to
      rule out CTS, ulnar nerve, root lesion, and to establish lower brachial plexus
      lesion before treating NTOS.

PMID- 16098810
TI  - Differences among the three major strains of Toxoplasma gondii and their specific
      interactions with the infected host.
AB  - Toxoplasma gondii is one of the most successful protozoan parasites owing to its
      ability to manipulate the immune system and establish a chronic infection. There
      are many T. gondii strains but the majority identified in Europe and North
      America falls into three distinct clonal lineages. Many studies have investigated
      the ability of T. gondii to manipulate its host but few have examined directly
      whether the three lineages differ in this ability.

PMID- 16098807
TI  - Bell's palsy-induced blepharospasm relieved by passive eyelid closure and
      responsive to apomorphine.
AB  - OBJECTIVE: We describe the case of a woman with Bell's Palsy-induced
      blepharospasm (BPIB) of the right eye that appeared simultaneously with a
      complete left facial nerve palsy. The involuntary spasm was relieved by passive
      lowering of the upper eyelid on the paretic side. METHODS: The recovery curve of
      the blink reflex was evaluated on the non-paretic side in baseline conditions,
      after subcutaneous apomorphine and placebo administration and 8 months later, at
      recovery from the palsy. RESULTS: We found increased recovery of the test-R2
      responses at short interstimulus intervals at baseline, which was normalised by
      apomorphine but not by placebo. At recovery the blink reflex R2 recovery curve
      returned to normal. CONCLUSIONS: This report demonstrates for the first time a
      response of BPIB to a dopamine agonist. SIGNIFICANCE: Our findings are in
      agreement with an animal model of blepharospasm that suggests a combined role of
      weakness of the orbicularis oculi muscle and a dysfunction of the dopaminergic
      system in the pathogenesis of this disorder.

PMID- 16098812
TI  - The sylvatic cycle of Neospora caninum: where do we go from here?
AB  - Bovine abortions due to Neospora caninum infection are a major cattle-production
      problem worldwide. The parasite is readily maintained in cattle populations by
      vertical transmission. The domestic dog excretes oocysts in its feces and, after
      sporulation, these oocysts are infectious to cattle. Current control measures are
      aimed at culling infected cows and limiting the access of cattle to infective
      oocysts. The recent revelations that coyotes (Canis latrans) can excrete N.
      caninum oocysts in their feces and that white-tailed deer (Odocoileus
      virginianus) are natural intermediate hosts of the parasite demonstrate the
      existence of a sylvatic cycle of neosporosis in North America. This complicates
      parasite-prevention programs but opens many new and exciting avenues of research.
      Similar canid-ruminant sylvatic cycles might exist in other countries and, if so,
      need to be investigated.

PMID- 16098813
TI  - Plowing the atrium and growing thrombi: two cases of large atrial thrombi
      following ablative and surgical procedure for atrial fibrillation.
AB  - AIM: We present two patients with a large left atrial (LA) thrombus following
      invasive treatment for atrial fibrillation and inadequate anticoagulation.
      METHODS AND RESULTS: Case 1: A 30-year-old woman, with a one-year history of
      symptomatic paroxysmal atrial fibrillation resistant to medical therapy,
      underwent catheter ablation for atrial fibrillation. Three days after the
      procedure the patient presented with dizziness, fatigue, rapid atrial
      fibrillation with a sub-therapeutic INR. Transesophageal echocardiography (TEE)
      revealed a large LA thrombus. Case 2: A 59-year-old male, with severe mitral
      regurgitation and chronic atrial fibrillation, underwent mitral valve repair and
      Cox-Maze procedure. Three months later, while asymptomatic, a follow-up
      transthoracic echocardiography a large posterior LA thrombus was imaged. His INR
      was also sub-therapeutic. Both patients were treated by enhancing anticoagulation
      and close echocardiographic follow-up. So far both patients have remained
      asymptomatic two months following discharge. CONCLUSION: Large LA thrombi
      detected by transthoracic echocardiography are a rare complication of the Cox
      Maze procedure and radio-frequency ablation for atrial fibrillation, which may
      occur even in patients with restored normal sinus rhythm receiving inadequate
      anticoagulation therapy.

PMID- 16098806
TI  - FTIR, Raman spectra and ab initio calculations of 2-mercaptobenzothiazole.
AB  - FTIR and Raman spectra of a rubber vulcanization accelerator, 2
      mercaptobenzothiazole (MBT), were recorded in the solid phase. The harmonic
      vibrational wavenumbers, for both the toutomeric forms of MBT, as well as for its
      dimeric complex, have been calculated, using ab initio RHF and density functional
      B3LYP methods invoking different basis sets upto RHF/6-31G** and B3LYP/6-31G**
      and the results were compared with the experimental values. Conformational
      studies have been also carried out regarding its toutomeric monomer forms and its
      dimer form. With all the basis sets the thione form of MBT (II) is predicted to
      be more stable than thiol form (I) and dimeric conformation (III) is predicted to
      be more stable with monomeric conformations (I) and (II). Vibrational assignments
      have been made, and it has been found that the calculated normal mode frequencies
      of dimeric conformation (III) are required for the analysis of IR and Raman bands
      of the MBT. The predicted shift in NH- stretching vibration towards the lower
      wave number side with the B3LYP/6-31G** calculations for the most stable dimer
      form (III), is in better agreement with experimental results. The intermolecular
      sulfur-nitrogen distance in N-H...S hydrogen bond was found to be 3.35 angstroms
      from these calculations, is also in agreement to the experimental value.

PMID- 16098811
TI  - The Entamoeba histolytica genome: something old, something new, something
      borrowed and sex too?
AB  - The recent publication of the protozoan parasite Entamoeba histolytica genome
      provides new insights into eukaryotic evolution, the role of lateral gene
      transfer in amebic biology and the adaptations required for eukaryotes that
      reside within the human intestine.

PMID- 16098816
TI  - New facets of the neuropathology and molecular profile of human temporal lobe
      epilepsy.
AB  - This review summarizes the salient features of the anatomical and molecular
      neuropathology of the hippocampus from patients with intractable temporal lobe
      epilepsy (TLE). It argues that sclerotic hippocampus is essential for seizure
      expression and that sclerosis is not a consequence of seizures, but is related to
      the epileptogenicity of the seizure focus. While neurons in sclerotic hippocampus
      may contribute to hippocampal hyperexcitability, this role is perhaps less
      important than that of the astrocytes. The astrocytes in sclerotic hippocampus
      may directly influence excitability through altered water homeostasis and K+
      buffering by redistribution of AQP4 transporters on their plasma membrane. It is
      proposed that they contribute to a high extracellular glutamate level through
      reduced glutamine synthetase, and activation through pro-inflammatory factors
      that release chemokines and cytokines, which enhance calcium-dependent glutamate
      release. Such a focal pool of glutamate may diffuse to surrounding neuron-rich
      areas to generate seizure activity in TLE.

PMID- 16098817
TI  - Metallothionein concentration in sponges (Spongia officinalis) as a biomarker of
      metal contamination.
AB  - The synthesis of metallothioneins (MTs) is often induced when organisms are
      exposed to heavy metals in the field. They are among the major "specific"
      biomarkers identified to date. With a view to include MTs in biomonitoring
      programs, the organisms most commonly studied are bivalves. Sponges present most
      of the characteristics researched in bioindicators of pollution and consequently
      have been proposed to constitute a "Sponge Watch Program". The detection of large
      quantities of metals in sponges suggests the existence of detoxification systems
      and indeed, the presence of metallothionein-like proteins (MTLPs) has been
      reported in two different species of sponges. In Spongia officinalis, the present
      study has demonstrated the presence of compounds exhibiting most of the
      characteristics of MTs: cytosolic, heat-stable, with apparent molecular mass of 4
      to 15 kDa and binding (at least) Ag, Cu and Zn. Specimens have been collected
      along the French Mediterranean coast from three sites differing by their degree
      of contamination. Relationships between MTLP and metal concentrations have been
      established. For copper, mercury and zinc, the correlations were significantly
      positive.

PMID- 16098814
TI  - Global and regional left ventricular function assessment with 16-detector row CT:
      comparison with echocardiography and cardiovascular magnetic resonance.
AB  - AIMS: To compare multidetector row computed tomography (MDCT) global and regional
      left ventricular (LV) function assessment with echocardiography and
      cardiovascular magnetic resonance (CMR). METHODS AND RESULTS: In 25 patients, who
      were referred for noninvasive angiography with 16-detector row CT, LV function
      assessment was also performed. A subsequent echocardiogram was performed, and in
      a subgroup of patients, CMR examination was completed to evaluate LV function.
      For global function assessment, the LV ejection fraction (LVEF) was calculated.
      Regional LV function was scored using a 17-segment model and a 4-point scoring
      system. MDCT agreed well with echocardiography for the assessment of LVEF
      (r=0.96; bias 0.54%; p<0.0001) and regional LV function (kappa=0.78). Eight
      patients had no contra-indications and gave informed consent for CMR examination.
      A fair correlation between MDCT and CMR was demonstrated in the assessment of
      LVEF (r=0.86; bias -1.5%; p<0.01). Regional LV function agreement between MDCT
      and CMR was good (kappa=0.86). CONCLUSION: MDCT agreed well with both
      echocardiography and CMR in the assessment of global and regional LV function.
      Global and regional LV function may accurately be evaluated by 16-detector row
      CT, and can be added to a routine CT image analysis protocol without need for
      additional contrast or imaging time.

PMID- 16098818
TI  - Isolation and characterization of light-dependent hemolytic cytotoxin from
      harmful red tide phytoplankton Chattonella marina.
AB  - Chattonella marina (C. marina), a raphidophycean flagellate, is a causative
      organism of red tide, and highly toxic to fish. In this study, we found that the
      cell-free methanol extract prepared from this flagellate exhibited potent
      hemolytic activity against rabbit erythrocytes. Interestingly, the hemolytic
      activity of the extract was absolutely light-dependent, and no hemolytic activity
      was detected in the dark even at very high concentration. Gel filtration
      chromatography of the methanol extract on a column of Sephadex LH-20 revealed
      that the extract contained hemagglutinin as well as hemolytic agents, and the
      substances responsible for these activities were separately eluted. These results
      suggest that the hemagglutinating and hemolytic activities were derived from
      distinct compounds. The hemolytic fraction obtained after gel filtration (F4)
      caused marked inhibition of the growth of C. marina itself and other species of
      phytoplanktons. Furthermore, F4 showed a potent cytotoxicity toward various
      mammalian cultured cell lines including human tumor cells (HeLa cells) in a dose
      dependent manner. The cytotoxicity was also light-dependent, and no cytotoxic
      effect was exhibited in any cell lines tested in the dark. After further
      purification procedures via preparative thin-layer chromatography and subsequent
      HPLC, a major hemolytic agent was obtained as highly purified form. Since the
      methanol extracts prepared from other raphidophycean flagellates such as
      Heterosigma akashiwo, Olisthodiscus luteus, and Fibrocapsa japonica showed light
      dependent hemolytic activity toward rabbit erythrocytes, it was suggested that
      the light-dependent hemolytic agents commonly exist at least in these
      raphidophycean flagellates.

PMID- 16098819
TI  - Using software agents to preserve individual health data confidentiality in micro
      scale geographical analyses.
AB  - Confidentiality constraints often preclude the release of disaggregate data about
      individuals, which limits the types and accuracy of the results of geographical
      health analyses that could be done. Access to individually geocoded
      (disaggregate) data often involves lengthy and cumbersome procedures through
      review boards and committees for approval (and sometimes is not possible).
      Moreover, current data confidentiality-preserving solutions compatible with fine
      level spatial analyses either lack flexibility or yield less than optimal results
      (because of confidentiality-preserving changes they introduce to disaggregate
      data), or both. In this paper, we present a simulation case study to illustrate
      how some analyses cannot be (or will suffer if) done on aggregate data. We then
      quickly review some existing data confidentiality-preserving techniques, and move
      on to explore a solution based on software agents with the potential of providing
      flexible, controlled (software-only) access to unmodified confidential
      disaggregate data and returning only results that do not expose any person
      identifiable details. The solution is thus appropriate for micro-scale
      geographical analyses where no person-identifiable details are required in the
      final results (i.e., only aggregate results are needed). Our proposed software
      agent technique also enables post-coordinated analyses to be designed and carried
      out on the confidential database(s), as needed, compared to a more conventional
      solution based on the Web Services model that would only support a rigid, pre
      coordinated (pre-determined) and rather limited set of analyses. The paper also
      provides an exploratory discussion of mobility, security, and trust issues
      associated with software agents, as well as possible directions/solutions to
      address these issues, including the use of virtual organizations. Successful
      partnerships between stakeholder organizations, proper collaboration agreements,
      clear policies, and unambiguous interpretations of laws and regulations are also
      much needed to support and ensure the success of any technological solution.

PMID- 16098822
TI  - Fluid retention mediated by renal PPARgamma.
AB  - Thiazolidinediones are activators of the nuclear receptor PPARgamma with proven
      efficacy on glucose homeostasis. However, treatment with these drugs often
      results in fluid retention and edema. Recent studies establish a role for
      PPARgamma in renal sodium reabsorption, providing a mechanism for the plasma
      volume expansion induced by these drugs.

PMID- 16098820
TI  - Detection of mercaptopyridines and mercaptopyrimidines in planar chromatography
      with iodine-azide reaction as a detection system.
AB  - Reaction between iodine and azide ion induced by mercaptopyridines and
      mercaptopyrimidines was utilized as a detection system in TLC and HPTLC. The
      developed plates were sprayed with a freshly prepared mixtures of sodium azide
      and starch solution adjusted to pH 5.5, and exposed to iodine vapour. The spots
      became visible as white spots on violet-grey background. The iodine-azide
      detection system has been proved to be the most favourable and enabled to detect
      quantities per spot in the range of 1-20 pmol (HPTLC) and 1-60 pmol (TLC). The
      iodine-azide tests were compared with other visualizing techniques commonly used
      in planar chromatography (iodine vapour and UV254). The developed method was
      applied to detection of thiopental in biological samples.

PMID- 16098821
TI  - Multigenerational exposure to genistein does not increase bone mineral density in
      rats.
AB  - Genistein has been shown to prevent bone loss in ovariectomized adult rats.
      However, the effects of genistein on bone in developing and reproductively-intact
      rats have not been examined. A large multigenerational experiment involved
      feeding 0, 5, 100, or 500 ppm genistein in the diet to intact male and female
      rats from conception until either weaning, postnatal day 140, or continuously for
      2 years. Vertebrae (lumbar and caudal) were collected from these animals at
      necropsy at 2 years of age and subjected to dual-energy x-ray absorptiometry
      (DXA) scanning to measure bone mineral density (BMD), bone mineral content (BMC),
      and bone area. Femurs were collected, and length, cross-sectional area, and
      cortical bone area were measured directly. Serum was collected for measurement of
      pyridinoline (PYD) and alkaline phosphatase (ALP). BMD was not affected by
      genistein in any phase of the experiment. In female rats treated continuously
      with genistein, BMC and bone area were reduced in the 500 ppm group compared to
      the 5 ppm group in the lumbar vertebrae, and in all treatment groups compared to
      control in the caudal vertebrae. In both males and females treated continuously,
      the cross-sectional area of the femur was reduced in rats treated with 500 ppm
      compared to those treated with 5 ppm. In female rats treated continuously, PYD
      was higher in the 100 and 500 ppm groups than in the 0 and 5 ppm groups. In
      conclusion, the effects of genistein on reproductively-intact rats were not
      dramatic. High dose of genistein throughout the lifespan resulted in decreased
      bone size, which may reduce the force required to break the bone.

PMID- 16098815
TI  - Sleep disturbances, socioeconomic status, and seizure control as main predictors
      of quality of life in epilepsy.
AB  - Improving quality of life is the most important goal for patients with epilepsy.
      To recognize the factors associated with quality of life in patients with
      epilepsy in Mexico, we performed a cross-sectional survey using the Quality of
      Life in Epilepsy 31 (QOLIE-31) inventory to assess the quality of life of 401
      adult patients with epilepsy at the National Institute of Neurology and
      Neurosurgery of Mexico. Clinical and demographical data were collected. Multiple
      regression was used to determine which factors affected quality of life in our
      patients. The variables that most strongly predicted a lower QOLIE-31 total score
      after multiple regression were sleep disorders (P<0.001), socioeconomic status
      (P<0.001), female gender (P=0.002), and high seizure frequency (P=0.001). In our
      study, neither depression nor time of evolution of epilepsy had significant
      influence on QOLIE-31 scores.

PMID- 16098823
TI  - Diabetic pancreatic beta cells ARNT all they should be.
AB  - A complex network of interacting transcription factors plays a critical role in
      normal pancreatic beta cell function, with mutations in certain transcription
      factor genes known to cause diabetes. In a recent issue of Cell, Gunton et
      al.(2005) demonstrate a role for the transcription factor ARNT/HIF1beta
      (hydrocarbon nuclear receptor translocator/hypoxia-inducible factor 1 beta) in
      normal beta cell function. ARNT expression is reduced in diabetic human islets
      and beta cell-specific ARNT knockout mice show the impaired glucose tolerance and
      abnormal insulin secretion that are characteristic of type 2 diabetes.

PMID- 16098824
TI  - A SIRTain role in pancreatic beta cell function.
AB  - Genes formerly thought to be involved solely in the regulation of life span have
      increasingly become implicated in the regulation of metabolic processes. Moynihan
      et al.(2005[this issue of Cell Metabolism]) now demonstrate that increasing
      levels of Sirt1 in the pancreatic beta cells of mice result in a more efficient
      glucose handling due to enhanced glucose-stimulated insulin secretion.

PMID- 16098825
TI  - Melting fat away in flies.
AB  - Two important proteins that function in regulating cell growth are the
      transcriptional regulator FOXO and the protein kinase Tor. A recent publication
      shows that the Melted protein can modulate both FOXO and Tor activity and can
      also regulate fat levels in Drosophila.

PMID- 16098826
TI  - Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3.
AB  - Evidence for the physiological functions of UCP2 and UCP3 is critically reviewed.
      They do not mediate adaptive thermogenesis, but they may be significantly
      thermogenic under specific pharmacological conditions. There is strong evidence
      that the mild regulated uncoupling they cause attenuates mitochondrial ROS
      production, protects against cellular damage, and diminishes insulin secretion.
      Evidence that they export fatty acids physiologically is weak. UCP2 and UCP3 are
      important potential targets for treatment of aging, degenerative diseases,
      diabetes, and perhaps obesity.

PMID- 16098827
TI  - Identification of SH2-B as a key regulator of leptin sensitivity, energy balance,
      and body weight in mice.
AB  - Leptin regulates energy balance and body weight by activating its receptor LEPRb
      and multiple downstream signaling pathways, including the STAT3 and the IRS2/PI 3
      kinase pathways, in the hypothalamus. Leptin stimulates activation of LEPRb
      associated JAK2, which initiates cell signaling. Here we identified SH2-B, a JAK2
      interacting protein, as a key regulator of leptin sensitivity, energy balance,
      and body weight. SH2-B homozygous null mice were severely hyperphagic and obese
      and developed a metabolic syndrome characterized by hyperleptinemia,
      hyperinsulinemia, hyperlipidemia, hepatic steatosis, and hyperglycemia. The
      expression of hypothalamic orexigenic NPY and AgRP was increased in SH2-B(-/-)
      mice. Leptin-stimulated activation of hypothalamic JAK2 and phosphorylation of
      hypothalamic STAT3 and IRS2 were significantly impaired in SH2-B(-/-) mice.
      Moreover, overexpression of SH2-B counteracted PTP1B-mediated inhibition of
      leptin signaling in cultured cells. Our data suggest that SH2-B is an endogenous
      enhancer of leptin sensitivity and required for maintaining normal energy
      metabolism and body weight in mice.

PMID- 16098828
TI  - Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose
      stimulated insulin secretion in mice.
AB  - Sir2 NAD-dependent deacetylases connect transcription, metabolism, and aging.
      Increasing the dosage or activity of Sir2 extends life span in yeast, worms, and
      flies and promotes fat mobilization and glucose production in mammalian cells.
      Here we show that increased dosage of Sirt1, the mammalian Sir2 ortholog, in
      pancreatic beta cells improves glucose tolerance and enhances insulin secretion
      in response to glucose in beta cell-specific Sirt1-overexpressing (BESTO)
      transgenic mice. This phenotype is maintained as BESTO mice age. Pancreatic
      perfusion experiments further demonstrate that Sirt1 enhances insulin secretion
      in response to glucose and KCl. Microarray analyses of beta cell lines reveal
      that Sirt1 regulates genes involved in insulin secretion, including uncoupling
      protein 2 (Ucp2). Isolated BESTO islets also have reduced Ucp2, increased ATP
      production, and enhanced insulin secretion during glucose and KCl stimulation.
      These findings establish the importance of Sirt1 in beta cell function in vivo
      and suggest therapeutic interventions for type 2 diabetes.

PMID- 16098830
TI  - Enhancing hepatic glycolysis reduces obesity: differential effects on lipogenesis
      depend on site of glycolytic modulation.
AB  - Reducing obesity requires an elevation of energy expenditure and/or a suppression
      of food intake. Here we show that enhancing hepatic glycolysis reduces body
      weight and adiposity in obese mice. Overexpression of glucokinase or 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatase is used to increase hepatic
      glycolysis. Either of the two treatments produces similar increases in rates of
      fatty acid oxidation in extrahepatic tissues, i.e., skeletal muscle, leading to
      an elevation of energy expenditure. However, only 6-phosphofructo-2
      kinase/fructose-2,6-bisphosphatase overexpression causes a suppression of food
      intake and a decrease in hypothalamic neuropeptide Y expression, contributing to
      a more pronounced reduction of body weight with this treatment. Furthermore, the
      two treatments cause differential lipid profiles due to opposite effects on
      hepatic lipogenesis, associated with distinct phosphorylation states of
      carbohydrate response element binding protein and AMP-activated protein kinase.
      The step at which hepatic glycolysis is enhanced dramatically influences overall
      whole-body energy balance and lipid profiles.

PMID- 16098833
TI  - Detection of change in shape and its relation to part structure.
AB  - Using a change detection paradigm (Barenholtz, E., Cohen, E. H., Feldman, J., &
      Singh, M. (2003). Detection of change in shape: An advantage for concavities.
      Cognition, 89(1) 1-9), we measured sensitivity to the changes of shapes and in
      particular the difference between detecting a new convex or concave vertex. We
      conclude that concave vertices per se are not more salient, but changes in the
      sequence of convexities and concavities along a contour are salient. We argue
      that these changes are likely to signal a change in perceived part structure.

PMID- 16098834
TI  - Impending epidemic of obesity, metabolic syndrome and diabetes mellitus--the role
      of prevention. Proceedings of a symposium, Tucson, Arizona, USA, September 30
      October 2, 2004.

PMID- 16098832
TI  - Accessory stimulation in the time course of visuomotor information processing:
      stimulus intensity effects on reaction time and response force.
AB  - A series of three visual choice-reaction time experiments were performed to
      systematically investigate the effects of accessory auditory stimulation on
      response time (RT) and response force (RF). In Experiment 1, the effect of
      accessory auditory stimulation on early visual information processing was
      investigated. Experiments 2 and 3 were designed to examine the effects of
      accessory intensity on RT and RF across the entire time course of sensorimotor
      processing. Accessory stimulation accelerated response speed only when presented
      within 100 ms after onset of the visual response signal. An enhancing effect of
      accessory stimulation on RF, however, was found as late as 220 ms after onset of
      the response signal. These findings support the notion that response speed and
      response dynamics represent functionally independent sensorimotor phenomena.

PMID- 16098829
TI  - Role of Rho-kinase in regulation of insulin action and glucose homeostasis.
AB  - Accumulating evidence indicates an important role for serine phosphorylation of
      IRS-1 in the regulation of insulin action. Recent studies suggest that Rho-kinase
      (ROK) is a mediator of insulin signaling, via interaction with IRS-1. Here we
      show that insulin stimulation of glucose transport is impaired when ROK is
      chemically or biologically inhibited in cultured adipocytes and myotubes and in
      isolated soleus muscle ex vivo. Inactivation of ROK also reduces insulin
      stimulated IRS-1 tyrosine phosphorylation and PI3K activity. Moreover, inhibition
      of ROK activity in mice causes insulin resistance by reducing insulin-stimulated
      glucose uptake in skeletal muscle in vivo. Mass spectrometry analysis identifies
      IRS-1 Ser632/635 as substrates of ROK in vitro, and mutation of these sites
      inhibits insulin signaling. These results strongly suggest that ROK regulates
      insulin-stimulated glucose transport in vitro and in vivo. Thus, ROK is an
      important regulator of insulin signaling and glucose metabolism.

PMID- 16098831
TI  - Foxa2 integrates the transcriptional response of the hepatocyte to fasting.
AB  - Survival during prolonged food deprivation depends on the activation of hepatic
      gluconeogenesis. Inappropriate regulation of this process is a hallmark of
      diabetes and other metabolic diseases. Activation of the genes encoding
      gluconeogenic enzymes is mediated by hormone-responsive transcription factors
      such as the cyclic AMP response element binding protein (CREB) and the
      glucocorticoid receptor (GR). Here we show using cell-type-specific gene ablation
      that the winged helix transcription factor Foxa2 is required for activation of
      the hepatic gluconeogenic program during fasting. Specifically, Foxa2 promotes
      gene activation both by cyclic AMP, the second messenger for glucagon, and
      glucocorticoids. Foxa2 mediates these effects by enabling recruitment of CREB and
      GR to their respective target sites in chromatin. We conclude that Foxa2 is
      required for execution of the hepatic gluconeogenic program by integrating the
      transcriptional response of the hepatocyte to hormonal stimulation.

PMID- 16098835
TI  - Implications of the metabolic syndrome: the new epidemic.
AB  - On the basis of traditional risk factors, a large number of individuals in the
      United States can be classified as at intermediate risk for the development of
      ischemic heart disease. The diagnosis of the metabolic syndrome can help
      determine whether patients at intermediate risk should be considered for more
      aggressive risk-factor reduction. The measurement of novel risk factors, such as
      inflammatory markers, can identify a group of patients at high intermediate risk.
      The Adult Treatment Panel of the National Cholesterol Education Program suggests
      considering a more aggressive low-density lipoprotein cholesterol treatment goal
      in this group of individuals. In addition, the presence of the metabolic syndrome
      is highly predictive of the development of diabetes mellitus. A treatment
      strategy focusing on aerobic exercise and weight loss can help delay or prevent
      the development of diabetes and can help reduce cardiovascular risk. For
      significant risk reduction to be achieved, treatment strategies must focus on
      therapy for all risk factors, including dyslipidemia, hypertension, and insulin
      resistance.

PMID- 16098836
TI  - Assessing risk across the spectrum of patients with the metabolic syndrome.
AB  - The metabolic syndrome represents a constellation of interrelated risk factors
      that identify individuals at increased risk for the development of type 2
      diabetes mellitus and cardiovascular events. Currently, the major cardiovascular
      risk factors and validated risk-assessment tools do not adequately account for
      the increased cardiovascular risk that accompanies the metabolic syndrome. In
      prospective population studies, cardiovascular risk assessment in individuals
      with the metabolic syndrome is improved by measures of low-density lipoprotein
      (LDL) particle number, C-reactive protein, and plasminogen activator inhibitor-1
      levels. Although adiponectin and soluble tumor necrosis factor receptor-2 may be
      more integrally involved in insulin resistance, the studies with these biomarkers
      are less extensive. Risk assessment models for patients with the metabolic
      syndrome should consider inclusion of LDL particle number, inflammatory markers,
      and levels of plasminogen activator inhibitor-1.

PMID- 16098838
TI  - Approach to treatment of the patient with metabolic syndrome: lifestyle therapy.
AB  - The National Cholesterol Education Program's Adult Treatment Panel III definition
      of the metabolic syndrome identifies those at high risk for diabetes mellitus
      and/or a cardiac event by clustering a number of easily measured clinical
      findings, including abdominal obesity, elevated plasma levels of triglycerides,
      low plasma levels of high-density lipoprotein cholesterol, elevated fasting blood
      glucose, and elevated blood pressure. The presence of > or = 3 of these 5 risk
      factors justifies a diagnosis of the metabolic syndrome. This article focuses on
      root causes of the syndrome (atherogenic diet, sedentary lifestyle, and
      overweight/obesity) and highlights recent studies that demonstrate the
      effectiveness of therapeutic lifestyle changes in improving or preventing the
      components of the metabolic syndrome. We offer a practical approach with a focus
      that embraces not only patients, but also physicians and healthcare professionals
      as well as the larger healthcare system.

PMID- 16098837
TI  - Need for lifestyle intervention: how to begin.
AB  - The metabolic syndrome is the fastest growing disease entity in the world.
      Prevention and effective treatment emphasize lifestyle intervention, including
      healthful diet, physical activity, and pharmacologic agents to target specific
      risk factors. Weight loss improves all aspects of the metabolic syndrome and is a
      primary intervention target. Effective weight management also helps prevent the
      development of the metabolic syndrome. Lifestyle change strategies--including
      setting reasonable goals, raising awareness, confronting barriers to change,
      managing stress, cognitive restructuring, preventing relapse, and providing
      support--are the keys to long-term success.

PMID- 16098839
TI  - Management of dyslipidemia in patients with complicated metabolic syndrome.
AB  - As the prevalence of the metabolic syndrome increases, 2 comorbid conditions-
      hepatic steatosis and human immunodeficiency virus (HIV) lipodystrophy--have
      become difficult clinical challenges. Dyslipidemia in patients with nonalcoholic
      fatty liver disease or nonalcoholic steatohepatitis may improve with use of
      statins, fibrates, niacin, and thiazolidinediones, but the data are presently
      very limited. HIV lipodystrophy is associated with a marked risk of coronary
      artery disease (CAD), and more aggressive management of the dyslipidemia is
      likely necessary to improve the prognosis.

PMID- 16098841
TI  - Rationale for new American Diabetes Association Guidelines: are national
      cholesterol education program goals adequate for the patient with diabetes
      mellitus?
AB  - Both the American Diabetes Association (ADA) and the National Cholesterol
      Education Program (NCEP) consider type 2 diabetes mellitus to be a coronary
      artery disease (CAD) risk equivalent and thus suggest that patients with either
      diabetes or CAD should have their plasma levels of low-density lipoprotein (LDL)
      cholesterol lowered to <2.59 mmol/L (<100 mg/dL). Recently the NCEP issued a
      white paper suggesting an even lower plasma LDL cholesterol goal of <1.81 mmol/L
      (<70 mg/dL) for patients at high cardiovascular risk, including patients with
      diabetes. This rationale was based partly on the higher risk of future
      cardiovascular disease seen in patients who have diabetes with or without
      preexisting cardiovascular disease than in nondiabetic subjects with preexisting
      cardiovascular disease. Additionally, as reported in the Pravastatin or
      Atorvastatin Evaluation and Infection Therapy (PROVE-IT) study, high-dose lipid
      lowering therapy has been shown to further reduce CAD event rates compared with
      conventional therapy.

PMID- 16098840
TI  - Lipid management in patients with diabetes mellitus.
AB  - The prevalence of diabetes mellitus has been increasing dramatically in recent
      decades. This trend closely follows the marked increase in the prevalence of
      obesity in the United States. As the proportion of the population with diabetes
      increases, the need for prevention and therapy to reduce cardiovascular events in
      these patients becomes critically important. Although plasma glucose control is
      important in reducing microvascular complications due to diabetes, lipid
      management is essential in these patients to reduce the incidence of
      cardiovascular events. Adult patients with type 2 diabetes, in the absence of
      known coronary artery disease (CAD), have a similar 10-year risk for cardiac
      events as do patients without diabetes with established coronary disease. Recent
      clinical trials have highlighted the importance of aggressive plasma lipid
      lowering for both the primary and secondary prevention of atherosclerotic events
      in patients with diabetes. The likelihood of an ever-increasing diabetic patient
      population requires new systematic approaches to prevention as well as therapy
      for these patients and further development of a team approach by the medical
      community to optimize care despite limited resources.

PMID- 16098842
TI  - Basic approach to managing hyperglycemia for the nonendocrinologist.
AB  - The prevalence of type 2 diabetes mellitus is growing rapidly worldwide. Reducing
      the complications of diabetes requires aggressive management of multiple risk
      factors, including elevated blood pressure, abnormal plasma lipid levels, and
      elevated plasma glucose. Fortunately, numerous agents are available to control
      these risk factors. This review discusses the therapeutic options in managing
      hyperglycemia, including lifestyle, oral agents, and insulin.

PMID- 16098843
TI  - Systematic strategies for improved outcomes for the hyperglycemic hospitalized
      patient with diabetes mellitus.
AB  - Diabetes mellitus is reaching epidemic proportions in the United States. It is
      now the fourth most common comorbid condition complicating hospital discharges.
      There is a rapidly evolving body of literature assessing the short-term and long
      term effects of strict glycemic control in the hospital setting. Results from
      several landmark studies have challenged the long-held notion that stress
      hyperglycemia is beneficial. This article will focus on these studies, postulated
      mechanisms of action, and finally, description of an insulin infusion protocol
      developed at a community hospital for patients undergoing cardiac surgery.

PMID- 16098844
TI  - An approach to heart failure and diabetes mellitus.
AB  - Diabetes mellitus is a chronic progressive disease that results in microvascular
      and macrovascular complications. Diabetes is a significant independent risk
      factor for heart failure, and there are a substantial number of patients with
      diabetes and heart failure. Neurohormonal activation plays an important
      pathophysiologic role in insulin resistance, diabetes, cardiovascular events, and
      progression of heart failure. Pharmacologic intervention in these neurohormonal
      systems (ie, angiotensin-converting enzyme [ACE] inhibition, aldosterone
      antagonism, and beta-adrenergic blockade) has been shown to decrease the
      morbidity and mortality of diabetes and of heart failure. Despite this knowledge,
      ACE inhibitors, aldosterone antagonists, and beta-blockers are grossly
      underutilized, and deaths and hospitalizations due to heart failure have steadily
      increased. Guidelines for the management of heart failure recommend the use of
      ACE inhibitors and beta-blockers in patients with mild, moderate, and severe
      heart failure with or without diabetes. Aldosterone antagonists are recommended
      in severe heart failure and recent data also support their use in mild to
      moderate heart failure. Concerns about increased incidence of hypoglycemia,
      worsening dyslipidemia, and decreased insulin sensitivity with beta-blockers may
      be preventing physicians from prescribing these agents for their patients with
      diabetes who have heart failure. Beta-blockade, in conjunction with ACE
      inhibition and aldosterone antagonism, should be standard therapy for all
      patients with diabetes and heart failure. Furthermore, every effort should be
      made to ensure that eligible patients are treated with these evidence-based,
      guideline-recommended, life-prolonging therapies.

PMID- 16098845
TI  - Recent National Cholesterol Education Program Adult Treatment Panel III update:
      adjustments and options.
AB  - In the summer of 2004, an evidence-based update of the National Cholesterol
      Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines for
      management of hypercholesterolemia was published. This detailed assessment of 5
      major clinical trials, published since the ATP III report in 2001, was designed
      to provide guidance for physicians in decision making for patients at high risk
      and very high risk. We have tried to summarize this assessment by suggesting the
      following to clinicians: (1) Calculate global risk of coronary artery disease
      (CAD) to determine an overall strategy for cholesterol management. (2) Emphasize
      the benefits of diet, exercise, and weight control or therapeutic lifestyle
      change, especially in those with lifestyle risk factors. (3) Use 3-hydroxy-3
      methyglutaryl coenzyme A reductase inhibitors (statins) as first-line drugs to
      reduce risk of CAD and stroke in those at moderate to high risk. (4) If statins
      are prescribed, use moderate doses that reduce plasma levels of low-density
      lipoprotein (LDL) cholesterol by > or = 30% to 40%. (5) Strongly consider statin
      therapy in those with diabetes (with the exception of severe
      hypertriglyceridemia). (6) Consider LDL cholesterol-lowering drug therapy for
      lipids in older patients at risk. (7) Consider adding either a fibrate or
      nicotinic acid in high-risk patients with elevated plasma triglyceride values or
      low levels of plasma high-density lipoprotein cholesterol after statin therapy
      has achieved the LDL cholesterol goal. (8) Continue to treat those at low risk in
      similar fashion as before. This update is to inform current physician judgment in
      this area. Further clinical trial data that may modify or extend these
      recommendations are eagerly awaited.

PMID- 16098846
TI  - Pharmacologic options for aggressive low-density lipoprotein cholesterol
      lowering: benefits versus risks.
AB  - Lessons from recent end point trials of lipid-lowering drugs indicate that
      patients at very high risk for coronary artery disease (CAD) benefit from
      treatment that lowers low-density lipoprotein (LDL) cholesterol plasma levels to
      < or = 1.81 mmol/L (< or = 70 mg/dL), that patients with > or = 2 risk factors
      benefit from treatment that lowers plasma LDL cholesterol to <2.59 mmol/L (<100
      mg/dL), and that a significant reduction in CAD event rates is most often
      associated with a minimum plasma LDL cholesterol reduction of 30%. Recently, the
      National Cholesterol Education Program (NCEP) Expert Panel on Detection,
      Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment
      Panel III) recommendations were amended to incorporate these lessons. To reach
      these more aggressive goals and plasma LDL cholesterol reductions, more
      aggressive therapies will be required. The best way to implement more aggressive
      therapy is to start with one of the more potent statins, especially atorvastatin
      or rosuvastatin, or higher doses of other statins. This approach alone is likely
      to achieve treatment goals in 50% to 80% of patients. For patients needing
      additional plasma LDL cholesterol lowering, combination therapies will be
      required. Adding colesevelam, ezetimibe, or niacin to a stable statin regimen
      will generally provide an additional 10% to 15% lowering of plasma LDL
      cholesterol. These more potent statins, even when used in higher doses, appear to
      be safe. The incidence of myopathy and rhabdomyolysis, as documented in long-term
      clinical trials, is <0.1% and <0.01%, respectively, except for simvastatin, which
      has a higher incidence of these problems. Less information is available about the
      safety of lowering levels of plasma LDL cholesterol to < or = 1.81 mmol/L (< or =
      70 mg/dL), but an analysis of a recent 2-year-long clinical trial, in which
      patients had on-treatment plasma LDL cholesterol levels as low as 0.67 mmol/L (26
      mg/dL), reported no signals of untoward effects in patients with progressively
      lower levels.

PMID- 16098847
TI  - Role of low-density lipoprotein apheresis.
AB  - Low-density lipoprotein (LDL) apheresis has been shown to reduce plasma levels of
      total cholesterol, LDL cholesterol, and lipoprotein(a). In addition to these
      lipoprotein changes, LDL apheresis induces atherosclerosis regression, improves
      myocardial perfusion and endothelial function, and may reduce cardiovascular
      event rates.

PMID- 16098848
TI  - Pathogenicity of periodontal pathogens during pregnancy.

PMID- 16098849
TI  - The effects of intra-amniotic injection of periodontopathic lipopolysaccharides
      in sheep.
AB  - OBJECTIVE: Periodontal disease may cause several complications of pregnancy,
      including fetal death. The purpose of this study was to investigate in sheep the
      effects of the intra-amniotic injection of lipopolysaccharide from 3
      periodontopathic organisms and to compare these effects with those resulting from
      similar injection of Escherichia coli lipopolysaccharide. The outcomes that were
      studied included the rates of fetal death and the features of inflammation and
      lung maturation in survivors. STUDY DESIGN: At 118 days of pregnancy, ewes that
      were bearing single fetuses were allocated at random to receive intra-amniotic
      injections of saline solution (n = 13 fetuses), or lipopolysaccharide from
      Porphyromonas gingivalis (in doses from 0.1 to 10 mg [n = 22 fetuses]),
      Actinobacillus actinomycetemcomitans (10 mg [n = 6 fetuses]; 1 mg [n = 6
      fetuses]), Fusobacterium nucleatum (10 mg [n = 6 fetuses]) or Escherichia coli
      (10 mg [n = 14 fetuses]; 1 mg [n = 7 fetuses]). Surviving fetuses were delivered
      abdominally at 125 days of gestation (term, 150 days). RESULTS: When compared
      with Escherichia coli lipopolysaccharide at similar dosages, periodontopathic
      lipopolysaccharides had high rates of fetal lethality. Only 6 of 22 fetuses that
      were exposed to intra-amniotic Porphyromonas gingivalis lipopolysaccharide
      survived doses of 0.1 to 10 mg, and only 3 of 6 fetuses survived 10-mg
      Actinobacillus actinomycetemcomitans lipopolysaccharide. Escherichia coli
      lipopolysaccharide did not cause fetal loss when given at doses of 10 mg (n = 14
      fetuses) or 1 mg (n = 7 fetuses). Fetuses that survived exposure to these
      lipopolysaccharides showed features of inflammation in amniotic fluid and cord
      blood at birth and enhanced lung maturation. CONCLUSION: Lipopolysaccharides from
      these 3 periodontopathic organisms have much higher rates of fetal lethality than
      Escherichia coli lipopolysaccharide but can cause similar intrauterine
      inflammatory responses and improvements in lung volumes in survivors. Sources of
      inflammation that are distant from the uterus may underlie a proportion of
      unexplained stillbirth and other complications of pregnancy.

PMID- 16098850
TI  - Evidence-based obstetric ethics and informed decision-making by pregnant women
      about invasive diagnosis after first-trimester assessment of risk for trisomy 21.
AB  - OBJECTIVE: The purpose of this study was to determine the ability of pregnant
      women to incorporate sophisticated screening information about risk assessment
      into their decisions about invasive testing in an appropriate way. STUDY DESIGN:
      Assessment of risk for trisomy 21 was carried out by a combination of maternal
      age, fetal nuchal translucency (NT) thickness, and maternal serum free beta-human
      chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein-A (PAPP-A)
      at 11 to 13+6 weeks. The patients were counseled with regards to their estimated
      risk, and were informed that the only way to know for sure whether or not the
      fetus has a chromosomal abnormality is by having an invasive test, but these
      tests carry a risk of miscarriage of about 1%. They were also informed that
      although a risk of 1 in 300 or more was generally considered to be high, it was
      up to them to decide in favor or against invasive testing. RESULTS: Assessment of
      risk was carried out in 30,564 singleton pregnancies with live fetuses at 11 to
      13+6. The median maternal age was 34 (range 15-49) years and, in 14,816 (48.5%),
      the age was 35 years or greater. The rate of invasive testing increased
      exponentially with increasing estimated risk (r = 0.917, P < .0001). The
      estimated risk for trisomy 21 was 1 in 300 or more in 2565 (8.4%) women, and 1991
      (77.6%) of these had invasive testing. The risk was less than 1 in 300 in 27,999
      (91.6%) women, and 1286 (4.6%) of these had invasive testing. CONCLUSION:
      Pregnant women are able to use sophisticated screening information to make
      scientifically and ethically rational decisions about invasive testing for
      trisomy 21. These empiric data compliment the arguments of normative ethics to
      create evidence-based ethical standards for informed consent regarding invasive
      testing.

PMID- 16098851
TI  - The decreased rates of triplet births: temporal trends and biologic speculations.
AB  - Recent data from the US and from England and Wales demonstrate decreasing rates
      of higher-order multiple births and represent, for the first time, a striking
      change in trend when compared with the previous steep 4-fold increase since the
      early 1980s. However, the incidence of other multiples--twins--continued to
      escalate. The most probable reasons for this change are new embryo transfer
      guidelines and availability of multi-fetal pregnancy reduction procedures.
      Because actual numbers of higher-order multiples are by far lower than the number
      of twins, and because twins are predictably associated with significant perinatal
      morbidity and mortality, the implications of the ever-increasing multiple birth
      rates are no less alarming. As long as the incidence of twins is not reduced, the
      decreasing incidence of higher-order multiples, per se, does not herald the end
      of the epidemic of multiple births.

PMID- 16098852
TI  - Suspicion and treatment of the macrosomic fetus: a review.
AB  - OBJECTIVE: To review the prevalence of and our ability to identify macrosomic
      (birthweight >4000 g) fetuses. Additionally, based on the current evidence,
      propose an algorithm for treatment of suspected macrosomia. STUDY DESIGN: A
      review. RESULTS: According to the National Vital Statistics, in the United
      States, the prevalence of newborns weighing at least 4000 g has decreased by 10%
      in seven years (10.2% in 1996 and 9.2% in 2002) and 19% for newborns with weights
      >5000 g (0.16% and 0.13%, respectively). Bayesian calculations indicates that the
      posttest probability of detecting a macrosomic fetus in an uncomplicated
      pregnancy is variable, ranging from 15% to 79% with sonographic estimates of
      birth weight, and 40 to 52% with clinical estimates. Among diabetic patients the
      post-test probability of identifying a newborn weighing >4000 g clinically and
      sonographically is over 60%. Among uncomplicated pregnancies, there is sufficient
      evidence that suspected macrosomia is not an indication for induction or for
      primary cesarean delivery. For pregnancies complicated by diabetes, with a prior
      cesarean delivery or shoulder dystocia, delivery of a macrosomic fetus increases
      the rate of complications, but there is insufficient evidence about the threshold
      of estimated fetal weight that should prompt cesarean delivery. CONCLUSION: Due
      to the inaccuracies, among uncomplicated pregnancies suspicion of macrosomia is
      not an indication for induction or for primary cesarean delivery.

PMID- 16098853
TI  - Raloxifene increases serum leptin levels in postmenopausal women: a prospective
      study.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of raloxifene
      on leptin and insulin-like growth factor-I levels and their relation with the
      biochemical markers of bone metabolism in postmenopausal women. STUDY DESIGN:
      Sixty-four women were given 60 mg/d raloxifene for 6 months. Serum leptin,
      insulin-like growth factor-I, alkaline phosphatase, calcium, osteocalcin, and
      collagen type I cross-link C-telopeptide levels were measured before and after
      the treatment. The patients were grouped as obese (body mass index, > or =25
      kg/m2) or non-obese (body mass index, <25 kg/m2). RESULTS: The mean basal leptin
      level was significantly higher (P < .001), and the mean cross-link C-telopeptide
      level was significantly lower (P = .001) in obese patients. Raloxifene therapy
      increased leptin levels (P < .001) and decreased insulin-like growth factor-I,
      alkaline phosphatase, and cross-link C-telopeptide levels significantly (P <
      .001). There was a strong negative correlation between leptin and cross-link C
      telopeptide (r = -0.703; P < .001). Insulin-like growth factor-I was not
      correlated with any parameter. CONCLUSION: Raloxifene increases serum leptin
      levels while decreasing bone resorption in postmenopausal women.

PMID- 16098854
TI  - Luteal phase dosing with paroxetine controlled release (CR) in the treatment of
      premenstrual dysphoric disorder.
AB  - OBJECTIVE: This clinical trial evaluated luteal phase dosing with paroxetine
      controlled release (CR) (12.5 mg and 25 mg) in the treatment of premenstrual
      dysphoric disorder (PMDD). STUDY DESIGN: A multicenter, randomized, double-blind,
      placebo-controlled, 3-arm, fixed-dose study of luteal phase dosing with
      paroxetine CR in the treatment of PMDD. Three hundred seventy-three patients with
      PMDD were randomly assigned into the study. The primary measure of efficacy was
      the change from baseline in the mean luteal visual analogue scale (VAS)-Mood
      score. Secondary efficacy measures included disorder-specific evaluations, global
      assessments of disease severity, and assessments of functional impairment.
      Adverse events were recorded throughout the trial. RESULTS: Patients treated with
      either dose of paroxetine CR demonstrated significantly greater improvements on
      the primary efficacy measure (change from baseline in mean luteal phase VAS-Mood
      scores) and on the majority of secondary efficacy measures compared with patients
      randomly assigned to placebo. CONCLUSION: For the treatment of PMDD, luteal phase
      dosing with 12.5 mg and 25 mg of paroxetine CR is effective and generally well
      tolerated.

PMID- 16098855
TI  - Common use of inaccurate antibody assays to identify infection status with herpes
      simplex virus type 2.
AB  - In recent proficiency testing of herpes simplex virus type-specific serologic
      evidence by the College of American Pathologists, commercially available herpes
      simplex virus antibody assays that were not glycoprotein-G based demonstrated
      high false-positive rates (14%-88%) for herpes simplex virus type-2 antibodies in
      sera that were positive for herpes simplex virus type-1 antibodies but negative
      for herpes simplex virus type-2 antibodies. Herpes simplex virus serologic
      testing should be performed with only glycoprotein-G-based tests.

PMID- 16098859
TI  - Comparison of transvaginal sonography with digital examination and transabdominal
      sonography for the determination of fetal head position in the second stage of
      labor.
AB  - OBJECTIVE: Precise determination of fetal head position in labor is a
      prerequisite for safe instrumental deliveries, and essential for the assessment
      of labor progress. Recent studies have cast serious doubts on the accuracy of the
      time-honored digital vaginal examination (DVE) in comparison to transabdominal
      ultrasound scans (TUS). However, transabdominal imaging is technically difficult
      with a deeply engaged fetal head in the second stage of labor. We examined the
      accuracy and time requirements of transvaginal scans (TVS) in the second stage of
      labor for determination of fetal head position. STUDY DESIGN: Sixty laboring
      women in the second stage of labor with a deeply engaged fetal head were examined
      by experienced nurse midwives and senior residents. Fetal head position was
      recorded as "time on a 12-hour clock." Subsequently, TUS and TVS were
      independently performed by a skilled sonographer. Accuracy and time requirements
      for all 3 examinations were recorded. RESULTS: Fetal head position could be
      determined in all cases by TVS, but not in 7 cases and 9 cases by DVE and TUS,
      respectively (P < .03; P < .008). A discrepancy of 60 degrees or more between the
      DVE and TUS or TVS was found in 13/60 cases (21.7%) and 14/60 cases (23.3%),
      respectively. A > or = 90 degrees discrepancy was found in 9/60 cases (15%) and
      12/60 cases (20%), respectively (P < .02 for comparison of TUS and TVS). In 5
      cases, the digital examination erroneously perceived an occiput posterior
      position as occiput anterior. No significant differences in fetal head position
      were detected between TUS and TVS, when the examination was technically feasible.
      The mean time (+/-SD) required for determining fetal head position was shortest
      for TVS (8.7 +/- 5.8 seconds) in comparison to DVE (22.7 +/- 14.6 seconds; P <
      .0001) or TAS (31.7 +/- 19.1 seconds; P < .0001). CONCLUSION: Transvaginal
      sonography was the most successful and accurate method for determination of fetal
      head position in the second stage of labor, and required the least time for
      performance. We believe that TVS should be routinely performed in the labor room
      setting for the determination of fetal head position.

PMID- 16098858
TI  - Aberrant methylation at HOXA10 may be responsible for its aberrant expression in
      the endometrium of patients with endometriosis.
AB  - OBJECTIVE: HOXA10, expressed in endometrium, plays an important role in uterine
      receptivity at the time of implantation. In the endometrium of women with
      endometriosis, its expression is reduced. The aim of this study was to determine
      whether the observed aberrant expression of HOXA10 is caused by aberrant
      methylation of the gene. STUDY DESIGN: Endometrial tissues were collected from 6
      women with laparoscopically confirmed endometriosis, and 4 women who underwent
      tubal ligation and were confirmed to have no endometriosis. In addition,
      menstrual blood from 5 women with no gynecologic complaints was collected and
      also used as controls. Methylation-specific polymerase chain reaction (PCR) and
      bisulfite sequencing were performed in 3 fragments in 2 regions of HOXA10 to
      detect difference in methylation patterns. Real-time reverse transcriptase (RT)
      PCR was also performed to measure expression levels of HOXA10 in select cases and
      controls. RESULTS: In all 3 fragments, there were highly statistically
      significant differences in methylation patterns between women with endometriosis
      and those without endometriosis. The expression level of HOXA10 was lower in
      women with endometriosis than those without, as previously reported. CONCLUSION:
      There is aberrant methylation in the endometrium of women with endometriosis
      compared with those without endometriosis. The aberrant methylation at HOXA10 may
      be responsible for the aberrant gene expression in the endometrium of women with
      endometriosis. This finding suggests that endometriosis may also be an epigenetic
      disease.

PMID- 16098856
TI  - High prevalence of viral genomes and inflammation in peripartum cardiomyopathy.
AB  - Molecular pathologic investigation of endomyocardial biopsy specimens from 26
      patients with peripartum cardiomyopathy revealed viral genomes (parvovirus B19,
      human herpes virus 6, Epstein-Barr virus, and human cytomegalovirus) in 8
      patients (30.7%) that were associated immunohistologically with interstitial
      inflammation. These findings indicate a high prevalence of virus-associated
      inflammatory changes in peripartum cardiomyopathy.

PMID- 16098857
TI  - Estrogen receptor-alpha thymidine and adenine repeat polymorphism and endothelial
      fibrinolytic regulation in postmenopausal women.
AB  - OBJECTIVE: We hypothesized that the capacity of the endothelium to release tissue
      type plasminogen activator is blunted in postmenopausal women with long (TA)(n)
      repeat alleles (> or = 18 repeats). STUDY DESIGN: Forty-two healthy
      postmenopausal women were studied: 10 women with short allele genotypes (both
      alleles, <18 repeats; age, 59 +/- 2 years), 8 women with long allele genotypes
      (both alleles, > or = 18 repeats; age, 59 +/- 3 years), and 24 women with mixed
      allele genotypes (1 short and 1 long allele; age, 56 +/- 1 years). Net
      endothelial tissue-type plasminogen activator release was determined in response
      to intra-arterial bradykinin and sodium nitroprusside. RESULTS: Tissue-type
      plasminogen activator release in response to bradykinin was highest in
      homozygotes for the short allele. The total amount of tissue-type plasminogen
      activator antigen that was released was significantly higher (>55%) in the short
      (452 +/- 68 ng/100 mL tissue) compared with the mixed (248 +/- 27 ng/100 mL
      tissue) and long allele (290 +/- 53 ng/100 mL tissue) groups. CONCLUSION: Our
      results demonstrate that the long (TA)n dinucleotide repeat allele is associated
      with blunted endothelial tissue-type plasminogen activator release in healthy
      postmenopausal women.

PMID- 16098860
TI  - Ultrasound evaluation of abnormal umbilical cord coiling in second trimester of
      gestation in association with adverse pregnancy outcome.
AB  - OBJECTIVE: The purpose of this study was to evaluate the antenatal umbilical cord
      coiling index obtained during the fetal anatomic survey in the second trimester
      as a predictor of adverse pregnancy outcome. STUDY DESIGN: Four hundred twenty
      five consecutive women who had a fetal anatomic survey between 18 to 23 weeks of
      gestation were evaluated for umbilical cord coiling. The antenatal umbilical cord
      coiling index was calculated as a reciprocal value of the distance between a pair
      of coils (antenatal umbilical cord coiling index = 1/distance in cm) and was
      correlated with the following adverse pregnancy outcomes: (1) small for
      gestational age, (2) mode of delivery, (3) presence of meconium-stained amniotic
      fluid, (4) presence of nonreassuring fetal status in labor, and (5) Apgar scores
      at 1 and 5 minutes. RESULTS: A total of 294 patients had adequate ultrasound
      images and all antenatal and labor data to meet the study inclusion criteria.
      Abnormal coiling was associated significantly with small for gestational age
      neonates at birth (P = .043) and non-reassuring fetal status in labor (P = .007).
      Nine of 58 neonates (15.5%) with abnormal umbilical coiling were small for
      gestational age infants compared with 15 of 236 small for gestational age
      neonates (6.4%) who had normal cord coiling. A non-reassuring fetal status in
      labor was observed in 25.7% of fetuses (15/58 fetuses) with abnormal umbilical
      coiling compared with 11.0% of fetuses (26/236 fetuses) with normal cord coiling.
      In contrast, no statistical difference for Apgar scores at 1 and 5 minutes or
      higher prevalence of interventional deliveries and meconium-stained amniotic
      fluid in labor between the groups with normal and abnormal umbilical cord coiling
      was observed. CONCLUSION: Abnormal umbilical cord coiling that is detected at the
      fetal ultrasound anatomic survey in the second trimester is associated with a
      higher prevalence of small for gestational age neonates and non-reassuring fetal
      status in labor. This observation can be used potentially as a predictor of
      adverse antenatal or perinatal events in future studies.

PMID- 16098861
TI  - The identification of risk of spontaneous fetal loss through second-trimester
      maternal serum screening.
AB  - OBJECTIVE: The purpose of this study was to investigate associations between risk
      of spontaneous fetal loss and risk estimates for Down syndrome, trisomy 18, and
      neural tube defects assigned by second-trimester maternal serum screening. STUDY
      DESIGN: The study involved 264,653 women with available pregnancy outcomes who
      were screened between 15 and 20 weeks of gestation in the Ontario Maternal Serum
      Screening Program between October 1995 and September 2000. Pregnancies
      complicated by fetal chromosomal or structural abnormalities, insulin-dependent
      diabetes mellitus, and multiple pregnancies were excluded. Spontaneous fetal loss
      was defined as spontaneous miscarriage and intrauterine fetal demise as
      classified by the ICD-9 system, but including only those > or = 15 weeks of
      gestation. Women were grouped according to risk estimates for Down syndrome,
      trisomy 18, and neural tube defects, respectively. Spontaneous fetal loss rates
      by each risk group were evaluated after adjusting for losses associated with
      maternal age and amniocentesis. RESULTS: Fetal loss rates increased in women with
      risk estimates of > or = 1 in 1110 for trisomy 18 or neural tube defects, and >
      or = 1 in 130 for Down syndrome. The excessive fetal loss rates for these 3
      groups of women were 14.4%, 3.2%, and 1.5% respectively. CONCLUSION: Fetal loss
      rate markedly increased in women with high-risk estimates for trisomy 18, neural
      tube defects, and Down syndrome. Risk estimates assigned by triple marker
      screening may provide an early means of stratifying pregnancies into risk for
      fetal loss.

PMID- 16098862
TI  - The use of cDNA microarray to identify differentially expressed labor-associated
      genes within the human myometrium during labor.
AB  - OBJECTIVE: Microarray technology was used to comprehensively analyze gene
      expression during human labor in the myometrium. STUDY DESIGN: cDNA micro-array
      was used to compare the transcriptomes of myometrium obtained from patients in
      spontaneous labor and those not in labor. Expression of four labor-specific genes
      was confirmed in the myometrium obtained from patients in spontaneous labor using
      RT-PCR, Northern blot analysis, and in-situ hybridization. RESULTS: Of the >6000
      cDNAs evaluated, 56 were found to be differentially expressed during labor. The
      labor-specific expression of 4 genes was confirmed using RT-PCR and Northern blot
      analysis. The relative increased expression of thrombospondin-1 in myometrium
      obtained from patients in spontaneous labor was also confirmed using in-situ
      hybridization. CONCLUSION: cDNA microarray was used to identify 56 differentially
      expressed genes in myometrium obtained from patients in spontaneous labor. The up
      regulation of four genes was confirmed by multiple methods. Elucidation of the
      role(s) of the genes identified by microarray should improve our understanding of
      normal labor physiology and may ultimately lead to more effective treatments for
      abnormal labor.

PMID- 16098863
TI  - Suboptimal neurodevelopment in very preterm infants is related to fetal
      cardiovascular compromise in placental insufficiency.
AB  - OBJECTIVE: The purpose of this study was to determine the relationship between
      fetal cardiovascular hemodynamics and neurodevelopmental outcome in infants born
      before 32 gestational weeks with placental insufficiency. STUDY DESIGN: Seventeen
      fetuses that underwent Doppler ultrasonography within 24 hours before delivery
      were included in this prospective cross-sectional study. Placental histology was
      examined. Multiple inflammatory markers and vascular endothelial growth factor
      (VEGF) and its receptor were analyzed from umbilical cord serum.
      Neurodevelopmental outcome was assessed by Griffiths scales at 1 year of
      corrected age. RESULTS: Infants with suboptimal outcome (n = 7) had higher
      umbilical artery, ductus venosus, and inferior vena cava pulsatility index values
      (P < .05) and lower weight-indexed cardiac outputs (P < .05) than infants with
      normal outcome (n = 10). Placental histology and serum revealed no inflammation.
      VEGF values were similar among all infants. CONCLUSION: In placental
      insufficiency with delivery before 32 gestational weeks, suboptimal
      neurodevelopment was related to decreased fetal weight-indexed cardiac output and
      increased systemic venous pressure.

PMID- 16098865
TI  - Genetic predispositions for thromboembolism as a possible etiology for
      gastroschisis.
AB  - OBJECTIVE: Occlusion of the omphalomesenteric artery in utero, leading to
      disruption of the umbilical ring with subsequent herniation of intestines, has
      been proposed as the mechanism by which gastroschisis occurs. We hypothesized
      that affected fetuses have a predisposition to arterial or venous
      thromboembolism. STUDY DESIGN: Thirty-one children born with gastroschisis were
      tested for Factor V Leiden, prothrombin, and methylene tetrahydrofolate reductase
      (MTHFR) mutations. Fifty-two appropriately grown term neonates whose mothers were
      matched by maternal age and race served as control neonates. RESULTS: Of children
      with gastroschisis, 6.45% were heterozygous for Factor V Leiden. No infants with
      gastroschisis had prothrombin gene mutations. Thirty-six percent of affected
      infants were heterozygous, and 16% were homozygosity for MTHFR. Among control
      infants, 42% were heterozygous, and 14% were homozygous for MTHFR. CONCLUSION:
      The mutation rate for MTHFR did not differ in children with and without
      gastroschisis when mothers were matched by race and age.

PMID- 16098866
TI  - An integrated model for the prediction of preeclampsia using maternal factors and
      uterine artery Doppler velocimetry in unselected low-risk women.
AB  - OBJECTIVE: The purpose of this study was to develop a predictive model for
      preeclampsia. STUDY DESIGN: This was a prospective screening study for
      preeclampsia using uterine artery Doppler ultrasound in unselected low-risk
      singleton pregnancies at community hospitals in the UK (n = 32,157). Logistic
      regression models were developed and their predictive ability assessed using the
      area under the receiver operator curve (AROC). RESULTS: Six hundred twelve (2.0%)
      women developed preeclampsia, and 144 (0.5%) required early delivery (<34 weeks).
      A model using both maternal and ultrasound factors had an AROC of 0.798, which
      was higher than ultrasound alone (0.729, P < .0001) or maternal factors alone
      (0.712, P < .0001). In early onset disease, the ROC of ultrasound alone (0.922)
      was not significantly improved by adding maternal predictors (0.945, P = .27). In
      contrast, late onset disease was better predicted by the combined model (AROC
      0.798) than ultrasound alone (AROC 0.729, P < .0001) or maternal factors alone
      (AROC 0.712, P < .0001). CONCLUSION: The combination of uterine artery Doppler
      ultrasound and maternal factors provided the best estimate of risk.

PMID- 16098864
TI  - High levels of fetal cell-free DNA in maternal serum: a risk factor for
      spontaneous preterm delivery.
AB  - OBJECTIVE: This study was conducted to determine whether there is a relationship
      between the concentration of fetal cell-free DNA in maternal serum and the
      duration of pregnancy in women who are at high risk for preterm delivery because
      of either preterm labor or preterm premature rupture of the membranes. STUDY
      DESIGN: Sera were collected and frozen from 71 women with a male fetus. Maternal
      serum fetal cell-free DNA concentration was measured with the use of real-time
      polymerase chain reaction amplification of DYS1. Fetal cell-free DNA
      concentrations were converted to multiples of the median. The following groups
      were studied: group 1: women with preterm labor and intact membranes who were
      delivered at > or = 36 weeks of gestation (n = 21); group 2: women with preterm
      labor who were delivered at <36 weeks of gestation (n = 29); and group 3: women
      with preterm premature rupture of the membranes in labor (n = 20) or not in labor
      (n = 1) who were delivered prematurely (<36 weeks of gestation). Kaplan-Meier and
      Cox regression analyses were used to analyze the relationship between fetal cell
      free DNA concentrations and the likelihood of preterm delivery. RESULTS: A cut
      off value for fetal cell-free DNA of 1.82 multiples of the median was chosen for
      analysis. The cumulative rate of early preterm delivery (<30 weeks of gestation)
      was significantly higher for women with fetal cell-free DNA concentrations of >
      or = 1.82 multiples of the median than those with fetal cell-free DNA
      concentrations below this cut-off (45% [95% CI, 36%-74%] vs 18% [95% CI, 11%
      25%]; P = .008]. The cumulative rate of preterm delivery (<36 weeks of gestation)
      was also significantly higher at > or = 1.82 multiples of the median (73% [95%
      CI, 52%-93%] vs 66% [95% CI, 54%-79%]; P = .02). After adjustment for covariates,
      Cox analysis showed that fetal cell-free DNA at > or = 1.82 multiples of the
      mechanisms of disease that are associated with a mean hazard rate of delivery of
      1.57 (P = .005). CONCLUSION: High concentrations of fetal cell-free DNA in
      maternal serum are associated with an increased risk of spontaneous preterm
      delivery. This observation may have implications for the understanding of the
      mechanisms of disease that is associated with preterm labor.

PMID- 16098868
TI  - Previous maternal infection with Toxoplasma gondii and the risk of fetal death.
AB  - OBJECTIVE: The purpose of this study was to assess the association between
      previous maternal Toxoplasma gondii (T gondii) infection and risk of fetal death.
      STUDY DESIGN: This was a population-based prospective cohort of 29,912 pregnant
      women without acute T gondii infection in Norway. RESULTS: In the study
      population, 2937 (9.8%) women had evidence of previous maternal T gondii
      infection, and 299 (1.0%) had fetal deaths. We found no association between
      previous T gondii infection and risk of fetal death at > or = 20 weeks of
      gestation. We did find a trend for an increased risk of fetal death at > or = 16
      and <20 weeks of gestation. However, we noted no association between previous T
      gondii infection and risk of fetal death at all birth weight categories (> or =
      1000, > or = 500 and <1000, and <500 g). CONCLUSION: These data do not indicate
      an increased risk of fetal death at > or = 20 weeks of gestation in women with
      previous maternal T gondii infection.

PMID- 16098867
TI  - Early invasive diagnostic techniques in pregnant women who are infected with the
      HIV: a multicenter case series.
AB  - OBJECTIVE: Studies that mostly were conducted before the widespread use of
      combination antiretroviral treatments have reported that antenatal invasive
      procedures markedly increase the risk of human immunodeficiency virus vertical
      transmission. We aimed to evaluate the vertical transmission rate and other
      maternal and neonatal complications among women who were infected with human
      immunodeficiency virus who underwent antenatal invasive procedures during the
      second trimester of pregnancy and who were delivered after the advent of
      antiretroviral regimens. STUDY DESIGN: We conducted a multicenter case series of
      women who were infected with human immunodeficiency virus who underwent
      amniocentesis or chorionic villus sampling or cordocentesis during the second
      trimester of pregnancy and who were delivered after January 1, 1997. RESULTS:
      Sixty-three of 775 recruited women (8.1%) had performed early invasive diagnostic
      techniques . This rate has improved progressively from 4% in 1997 to 14%. Two of
      60 viable infants (3.3%; 95% CI, 0.6%-10.1%) were infected with the human
      immunodeficiency virus. This rate did not differ significantly from the
      transmission rate that was observed in women who did not undergo antenatal
      invasive techniques (1.7%; P = .30). CONCLUSION: The current risk of human
      immunodeficiency virus vertical transmission that is associated with early
      invasive diagnostic techniques is lower than previously reported.

PMID- 16098870
TI  - Racial/ethnic differences in perineal, vaginal and cervical lacerations.
AB  - OBJECTIVE: To determine if variation exists between ethnicities for risk of
      perineal, vaginal, and cervical laceration at vaginal delivery. STUDY DESIGN:
      Retrospective cohort study of nulliparous women who underwent vaginal delivery of
      a vertex presentation. Predictor variable was ethnicity with outcome variables
      cervical, vaginal, and second-, third-, or fourth-degree perineal laceration.
      Logistic regression analysis was conducted to control for confounders. RESULTS:
      Of the 17,216 who met criteria, Filipino (OR = 1.92, 95% CI 1.64-2.25) and
      Chinese (OR = 1.60, 95% CI 1.33-1.92) women were at greatest risk for third- and
      fourth-degree laceration. Only Filipino (OR = 1.32, 95% CI 1.10-1.57) and other
      Asian (OR = 1.23, 95% CI 1.08-1.41) women were at slightly increased risk of
      vaginal laceration. No differences were seen for cervical laceration. CONCLUSION:
      Different ethnicities are at widely varying risk of perineal laceration, but
      little difference exists for vaginal or cervical lacerations. Research into the
      mechanisms behind this should investigate differences in perineal anatomy.

PMID- 16098869
TI  - Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic
      women.
AB  - OBJECTIVE: B-type natriuretic peptide (BNP) is synthesized in cardiac ventricles
      in response to volume expansion. This study evaluated BNP levels to determine
      trends during pregnancy, and to assess BNP as a diagnostic tool in preeclampsia.
      STUDY DESIGN: We studied 163 BNP levels in 118 pregnant women, ranging from first
      trimester to term. An additional 34 patients with preeclampsia were studied and
      compared to 25 normal control patients at term. Plasma BNP values were determined
      using a standard assay. RESULTS: The median BNP levels during the 1st, 2nd, 3rd
      trimester, and at term were equivalent (18.4, 17.9, 15.5, and 17.8 pg/mL,
      respectively, P = .796). The median BNP levels in normal patients, mild
      preeclamptics, and severe preeclamptics were 17.8, 21.1, and 101 pg/mL,
      respectively, with the severe group being significantly higher than the mild
      group (P = .003) and any phase of normal pregnancy (P < .001 in each case). A BNP
      cut-off of <40.6 pg/mL had a negative predictive value of 92% in excluding
      preeclampsia. CONCLUSION: In normal pregnancies, median BNP values are <20 pg/mL,
      and stable throughout gestation. In severe preeclampsia BNP levels are elevated.
      This may reflect ventricular stress and/or subclinical cardiac dysfunction
      associated with preeclampsia.

PMID- 16098871
TI  - Development of a clinical prediction rule for iron deficiency anemia in
      pregnancy.
AB  - OBJECTIVE: The purpose of this study was to elucidate if anemia in pregnancy
      caused by iron deficiency could be predicted by simple measures obtained on a
      complete blood count (CBC) using ferritin as the gold standard. STUDY DESIGN: One
      hundred forty-one pregnant patients with anemia were recruited during their first
      prenatal visit. CBC and ferritin level were obtained and candidate-predictors
      identified. Receiver operator characteristic (ROC) curves, stratified analysis,
      and logistic regression analysis were used to develop a prediction rule with
      maximum specificity. RESULTS: A hemoglobin level < or = 9.7 and a red cell
      distribution width (RDW) > or = 15 (in gestational age <20 weeks) predicted iron
      deficiency with high specificity. Our final model correctly classified 79.43% of
      the patients (area under the ROC curve of 0.88 [95%CI 0.82-0.93], specificity of
      95.74%). CONCLUSION: Iron deficiency anemia can be predicted in pregnancy using
      lower cost tests, which could be an incredibly useful tool in areas with limited
      resources and a high prevalence of the disease. This study was limited to a
      mostly African American population in an urban setting, and the results may not
      be generalized to other populations.

PMID- 16098872
TI  - Racial disparity in fetal growth inhibition among singletons and multiples.
AB  - OBJECTIVE: The purpose of this study was to determine the magnitude of black
      white gap in intrauterine fetal growth inhibition among singletons and multiples.
      STUDY DESIGN: This was a cross-sectional study on singleton, twin, and triplet
      live births in the United States from 1995 through 1998. We compared the risk for
      low and very low-birth-weight, preterm and very preterm, and small-for
      gestational age between black and white neonates. RESULTS: A total of 14,245,865
      singletons (blacks = 16.2%), 392,761 twins (blacks = 18.0%), and 21,436 triplets
      (blacks = 7.7%) were analyzed. Black neonates depicted significantly higher risks
      for all indices of fetal growth inhibition regardless of plurality. The
      gestational age of onset of fetal growth lag for black fetuses was earliest among
      triplets (23 weeks and the gap remained unchanged) then singletons (26 weeks;
      maximum gap 37-42 weeks), and finally twins (33 weeks; maximum gap 37-40 weeks).
      CONCLUSION: Black-white disparity in fetal growth inhibition varied by plurality
      subtypes. The different gestational ages of onset of black-white fetal growth
      divergence could potentially be exploited for targeting intervention measures
      aimed at narrowing the gap.

PMID- 16098873
TI  - Increased risk of adverse pregnancy outcome among Somali immigrants in Washington
      state.
AB  - OBJECTIVE: The purpose of this study was to compare maternal and neonatal
      morbidity among Somali immigrants, US-born blacks and whites in Washington state.
      STUDY DESIGN: Washington state birth certificate data was linked to hospital
      discharge records comparing singleton deliveries among Somali immigrants with US
      born blacks and whites between 1993 and 2001, in a 1:3 ratio. Outcomes were
      compared using unconditional multiple logistic regression models calculating odds
      ratios (ORs), and 95% confidence intervals (95% CIs). RESULTS: Five hundred
      seventy-nine pregnancies from Somali women were compared with 2384 and 2435
      pregnancies from black and white women, respectively. Nulliparous Somali women
      were more likely to have a cesarean delivery than black or white control women,
      OR 1.6 (95% CI, 1.1-2.3) and 2.0 (95% CI, 1.4-2.8), respectively. Among all women
      who had cesarean deliveries, Somali women more commonly had cesarean deliveries
      associated with fetal distress and failed induction of labor. They were 9 times
      more likely than both control groups to deliver after 42 weeks gestation, and 4
      times more likely than black women and 8 times more likely than white women to
      have oligohydramnios. Somali women were more likely to have gestational diabetes
      and significant perineal lacerations, and less likely to smoke. Newborns of
      Somali women were at increased risk for prolonged hospitalization, lower 5-minute
      Apgar scores, assisted ventilation, and meconium aspiration. CONCLUSION:
      Pregnancy outcomes should be evaluated within ethnically and culturally unique
      groups; Somali immigrants are a high-risk subpopulation.

PMID- 16098874
TI  - Syncytiotrophoblast intercellular adhesion molecule-1 expression in placental
      villitis of unknown cause.
AB  - OBJECTIVE: The purpose of this study was to determine syncytiotrophoblast
      intercellular adhesion molecule-1 expression in villitis and in normal chorionic
      villi from term (37-42 weeks of gestation) placentas with or without villitis.
      STUDY DESIGN: A cross-sectional study was conducted to determine
      syncytiotrophoblast intercellular adhesion molecule-1 expression in villitis (n =
      16) and in normal villi from placentas with or without villitis (n = 16).
      Villitis was diagnosed with antibodies to human leukocyte antigen-DR and CD3 and
      hematoxylin and eosin staining of serial sections; intercellular adhesion
      molecule-1 reactivity in syncytiotrophoblast was confirmed with antibodies to
      intercellular adhesion molecule-1 and cytokeratin. RESULTS: Villitis lesions had
      higher syncytiotrophoblast intercellular adhesion molecule-1 expression than
      normal chorionic villi from placentas with (19.9% vs 3.5% villi; P < .001) or
      without (19.9% vs 0.31% villi; P < .001) villitis. Normal villi from placentas
      with villitis had higher syncytiotrophoblast intercellular adhesion molecule-1
      than villi from placentas without villitis (3.5% vs 0.31% villi; P < .001).
      CONCLUSION: Placentas with villitis have significantly more syncytiotrophoblast
      intercellular adhesion molecule-1 expression than placentas without villitis. The
      finding that normal villi from placentas with villitis have more
      syncytiotrophoblast intercellular adhesion molecule-1 than normal villi from
      placentas without villitis suggests that syncytiotrophoblast intercellular
      adhesion molecule-1 could be the first step in villitis development.

PMID- 16098875
TI  - Fetal deaths in the United States, 1997 vs 1991.
AB  - OBJECTIVE: The purpose of this study was to examine the temporal change in fetal
      death risk in the US from 1991 to 1997, and to assess the extent to which changes
      in registration practices and labor induction have contributed to that change.
      STUDY DESIGN: This was a cohort study of all singleton pregnancies 20 to 43 weeks
      of gestation in 1991 and 1997 in the US. RESULTS: From 1991 to 1997, the overall
      fetal death rate fell from 77.6 to 67.8 per 10,000 total births. However, fetal
      deaths at 20 to 22 weeks as a proportion of total births increased from 14.5 to
      16.9 per 10,000. In a Cox regression analysis, the crude period effect (1997 vs
      1991) at 40 to 43 weeks was 0.87 (95% CI 0.80-0.94), and remained virtually
      unchanged (HR 0.88, 95% CI 0.81-0.96) after adjustment for maternal
      sociodemographic, medical, and lifestyle risk factors. In ecologic (Poisson
      regression) analysis based on states as the unit of analysis, the crude period
      effect in non-Hispanic whites (RR 0.79, 95% CI 0.74-0.84) disappeared (RR 0.98,
      95% CI 0.82-1.16) after adjusting for induction of labor. The effect of induction
      in blacks was limited to 42 to 43 weeks in those at high risk. CONCLUSION:
      Increased registration is probably responsible for an increase in fetal death
      risk at 20 to 22 weeks of gestation, whereas the increasing trend toward routine
      labor induction at and after term appears to have reduced the risk of fetal
      death, especially among whites.

PMID- 16098876
TI  - Placental volume, as measured by 3-dimensional sonography and levels of maternal
      plasma cell-free fetal DNA.
AB  - OBJECTIVE: Measurement of cell-free fetal (cff) DNA in maternal plasma may have
      clinical application in prenatal screening for fetal Down syndrome and
      preeclampsia. Little is known regarding the tissue of origin of these fetal
      derived sequences. We tested the hypothesis that if the placenta is the major
      contributor of cff DNA, then an increased placental volume should be associated
      with higher maternal plasma cff DNA levels. STUDY DESIGN: We enrolled 143
      pregnant women who underwent first-trimester placental volume measurement using 3
      dimensional ultrasonography. Cff DNA in maternal plasma on the day of the scan
      was quantified by real-time polymerase chain reaction (PCR) amplification of a Y
      chromosome sequence. The association between measured placental volume and
      maternal plasma cff DNA levels was analyzed along with relevant clinical
      variables. RESULTS: The median (25th, 75th percentiles) maternal plasma cff DNA
      level was 16.9 genome equivalents (GE)/mL (10.8, 28.7). Raw values were adjusted
      for gestational age and maternal body mass index. The median (25th, 75th
      percentiles) placental volume was 53.2 mL (43.0, 64.7), and median placental
      quotient (ratio of placental volume to fetal crown-rump length) was 1 mm2 (0.8,
      1.1). Based on multivariate linear regression analyses, neither of the above
      placental measurements showed a significant association with maternal plasma cff
      DNA levels (P = .43 and .43, respectively). A modest association was found
      between plasma cff DNA levels and gravidity (P = .03). CONCLUSION: Our data did
      not show a significant association between either the placental volume or
      placental quotient, and maternal plasma cff DNA levels. We speculate that it is
      the extent of placental apoptosis that primarily affects the amount of cff DNA
      released into the maternal circulation.

PMID- 16098878
TI  - Presidential address: human error, patient safety and the tort liability crisis:
      the perfect storm.

PMID- 16098877
TI  - Left atrial thrombosis in pregnant women with mitral stenosis and sinus rhythm.
AB  - OBJECTIVE: The purpose of this study was to describe pregnant patients with
      mitral stenosis who had intracardiac thrombosis in the absence of atrial
      fibrillation. STUDY DESIGN: We reviewed the clinical course of 3 pregnant women
      with severe mitral stenosis and normal sinus rhythm who had clinically
      significant intracardiac thrombosis. RESULTS: The first patient was examined at
      21 weeks of gestation with embolic stroke that was the result of left atrial
      thrombus. A second patient was found to have a large left atrial thrombus that
      prevented the performance of balloon valvuloplasty. The third patient had left
      atrial clot that partially occluded the mitral valve orifice and led to the
      development of pulmonary edema that resulted in an emergent cesarean delivery and
      anoxic brain injury in the newborn infant. CONCLUSION: Pregnant patients with
      mitral stenosis in normal sinus rhythm can experience thromboembolic events that
      can be detrimental to both the mother and the fetus. Anticoagulation therefore
      should be strongly considered in this group.

PMID- 16098879
TI  - The effect of pregnancy and mode of delivery on the prevalence of urinary and
      fecal incontinence.
AB  - OBJECTIVE: The purpose of this study was to determine the relative effects of
      pregnancy and mode of delivery on the prevalence of urinary and fecal
      incontinence. STUDY DESIGN: This was a prospective, observational multicenter
      study of women presenting to 6 gynecology clinics. Demographic data collected
      included: height, weight, gravidity, parity, and number of vaginal deliveries.
      Patients were diagnosed with incontinence by questionnaire. Standard univariate
      logistic regression analyses' were performed to determine the contribution of
      pregnancy, mode of delivery, and BMI on the prevalence of urinary and fecal
      incontinence. RESULTS: One thousand and four women were enrolled over an 18-month
      period. Two hundred and thirty-seven and 128 subjects had urinary and fecal
      incontinence, respectively. Odds ratio (95% CI) calculated for the prevalence of
      urinary incontinence by pregnancy and mode of delivery were: any term pregnancy
      vs no term pregnancy was 2.46 (1.53-3.95), any term pregnancy but no vaginal
      deliveries (cesarean section only) vs no term pregnancy was 1.95 (0.99-3.80), any
      term pregnancy and at least 1 vaginal delivery vs no term pregnancy was 2.53
      (1.57-4.07), and any term pregnancy but no vaginal delivery (cesarean section
      only) vs any term pregnancy, and at least 1 vaginal delivery was 1.30 (0.77
      3.95). Odds ratio (95% CI) calculated for the prevalence of fecal incontinence by
      pregnancy and mode of delivery were: any term pregnancy vs no term pregnancy was
      2.26 (1.22-4.19), any term pregnancy but no vaginal deliveries (cesarean section
      only) vs no term pregnancy was 1.13 (0.43-2.96), any term pregnancy and at least
      1 vaginal delivery vs no term pregnancy was 2.41 (1.30-4.49), and any term
      pregnancy but no vaginal deliveries (cesarean section only) vs any term
      pregnancy, and at least 1 vaginal delivery was 2.15 (0.97-4.77). BMI and age did
      not impact these results. CONCLUSION: Pregnancy increases the risk of urinary and
      fecal incontinence. Cesarean section does not decrease the risk of urinary or
      fecal incontinence compared to pregnancy with a vaginal delivery.

PMID- 16098882
TI  - Notable presentations in the history of the South Atlantic Association of
      Obstetricians and Gynecologists.

PMID- 16098883
TI  - Occiput posterior fetal head position increases the risk of anal sphincter injury
      in vacuum-assisted deliveries.
AB  - OBJECTIVE: The purpose of this study was to determine whether an occiput
      posterior (OP) fetal head position increases the risk for anal sphincter injury
      when compared with an occiput anterior (OA) position in vacuum-assisted
      deliveries. STUDY DESIGN: We conducted a retrospective cohort study of 393 vacuum
      assisted singleton vaginal deliveries. Maternal demographics and obstetric and
      neonatal data were collected from an obstetric database and chart review.
      RESULTS: Within the OP group, 41.7% developed a third- or fourth-degree
      laceration compared with 22.0% in the OA group (OR 2.5, 95% CI 1.4-4.7). In a
      logistic regression model that controlled for BMI, race, nulliparity, length of
      second stage, episiotomy, birth weight, head circumference, and fetal head
      position, OP position was 4.0 times (95% CI 1.7-9.6) more likely to be associated
      with an anal sphincter injury than OA position. CONCLUSION: Among vacuum
      deliveries, an OP head position confers an incrementally increased risk for anal
      sphincter injury over an OA position.

PMID- 16098885
TI  - Differences in outcomes after third- versus fourth-degree perineal laceration
      repair: a prospective study.
AB  - OBJECTIVE: The purpose of this study was to compare outcomes after third- versus
      fourth-degree laceration repair. STUDY DESIGN: Fifty-six primiparous women who
      sustained a third- or fourth-degree tear were enrolled at delivery and
      demographic and obstetric data were collected. At 6 weeks' postpartum, subjects
      completed a bowel function questionnaire and endoanal ultrasonography was
      performed. Fisher exact test and chi-square were used for statistical analysis.
      RESULTS: Thirty-nine women with third- and 17 with fourth-degree tears were
      enrolled. Subjects with fourth- were more likely to report bowel symptoms (59% vs
      28%, P = .03), and to demonstrate persistent combined defects of the internal
      (IAS) and external anal sphincter (EAS) (48% vs 8%, P = .002) than third-degree
      tears. Combined defects were associated with the highest risk of bowel symptoms
      (OR 18.7, 95% CI 3-101, P < .001). CONCLUSION: Bowel symptoms were more common
      after fourth- than third-degree repair, and may be secondary to higher rates of
      combined defects of the IAS and EAS.

PMID- 16098887
TI  - The use of non-nutritive sucking to decrease the physiologic pain response during
      neonatal circumcision: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this research was to study the effects on the
      physiologic pain response of the neonate during circumcision with the use of a
      gloved human finger. STUDY DESIGN: This was a randomized controlled trial
      analyzing the effect of non-nutritive sucking (NNS) on pain response during
      circumcision. Term neonates were randomized to 2 groups. All infants received
      oral Tylenol and a dorsal penile nerve block (DPNB) before the circumcision. The
      study group was offered the addition of NNS before the DPNB and throughout the
      procedure. The primary outcome measured was heart rate during the circumcision.
      Other variables studied included crying time and salivary cortisol levels. Each
      circumcision was filmed to calculate pain profile scores using the Premature
      Infant Pain Profile. Variables were compared using Student t test, chi-square,
      and Wilcoxon test. A P value of < .05 was considered significant. RESULTS: Forty
      four infants met inclusion criteria. Twenty-two infants were randomized to each
      arm. No difference in mean heart rate during the procedure was apparent. A
      significant decrease in crying time, 90-minute post-procedure salivary cortisol
      level, and post-penile clamping pain score was noted in the study group (all P
      values < .01). CONCLUSION: NNS significantly decreases some elements of
      measurable physiologic pain response of the neonate during circumcision. This
      method is a useful and inexpensive addition to DPNB and oral analgesics.

PMID- 16098889
TI  - Outcomes of second-trimester pregnancy terminations with misoprostol: comparing 2
      regimens.
AB  - OBJECTIVE: The purpose of this study was compare outcomes of second-trimester
      pregnancy terminations with misoprostol between our previous low- (200 microg
      every 12 h) and present high-dose (400 microg every 6 h) regimens. STUDY DESIGN:
      This was an historic cohort study that was conducted from June 1996 to February
      2004 on women undergoing medical termination of pregnancy at 13 to 27 weeks.
      Exclusion criteria were multiple gestation, placenta previa, and primary use of
      another medication. RESULTS: The cohort consisted of 147 women. For the low- (n =
      100) and high-dose (n = 47) groups, respectively, median times to delivery were
      22.5 vs 13.25 hours (P = .001). More patients in the high-dose group were
      delivered vaginally within 24 (81% vs 54%; P = .002) and 48 hours (98% vs 84%; P
      = .014). Fewer patients in the high-dose group required a second abortifacient
      (6% vs 27%; P = .004). Clinical chorioamnionitis was more common in the high-dose
      group (P = .03). One patient experienced a uterine rupture and is included in the
      analysis. Side effects were uncommon and did not differ between groups.
      CONCLUSION: Our present high-dose regimen for misoprostol terminations of
      pregnancy effects delivery more rapidly without an appreciable increase in side
      effects or complications.

PMID- 16098892
TI  - Assessment of the understanding of the risks and benefits of hormone replacement
      therapy (HRT) in primary care physicians.
AB  - OBJECTIVE: This study was designed to assess the understanding of primary care
      physicians who practice in the state of Florida of the risks and benefits of
      hormone replacement therapy as described in the Women's Health Initiative
      clinical trial. STUDY DESIGN: All primary care physicians in the state of
      Florida, including family practice, internal medicine, and Ob/Gyn were identified
      and mailed an anonymous survey asking about their understanding of the risks and
      benefits of hormone replacement therapy (HRT), including heart disease, breast
      cancer, osteoporotic fractures, colon cancer, stroke, and death. Univariate
      statistics stratified by specialty were performed with Kruskal-Wallis one-way
      analysis of variance. RESULTS: Six thousand one hundred twenty-five surveys were
      mailed, with the return of 600 completed surveys, including 203 Ob/Gyn, 145
      internal medicine, 219 family practice, and 33 other. Overall, Ob/Gyns had a more
      positive view of HRT, and internal medicine had a relatively negative view of
      HRT. In general, respondents overestimated the risk attributable to hormone
      replacement therapy. Ob/Gyns were significantly more likely to provide accurate
      assessments of these risks and benefits compared with the other specialties.
      Respondents correctly identified the magnitude of risks and benefits 28% of the
      time, 67% of the time overestimated risks and benefits, and 5% of the time
      misunderstood the direction of risk vs benefit of HRT. CONCLUSION: This study
      suggests that the findings of the Women's Health Initiative are misunderstood by
      the majority of primary care specialists, although Ob/Gyns have a better
      understanding of the risks and benefits compared to other specialties. We
      hypothesize that respondents that overestimate the increase or decrease in risk
      were making the error of confusing relative risk with absolute risk difference.
      There is a great need for physician education about the attributable risks and
      benefits of HRT.

PMID- 16098895
TI  - The utility of HPV DNA triage in the management of cytological AGC.
AB  - OBJECTIVE: Given the demonstrated utility of human papilloma virus DNA triage in
      the management of atypical squamous cells of undetermined significance, this
      study sought to evaluate the potential role of human papilloma virus DNA testing
      in the evaluation and management of cytological atypical glandular cells. STUDY
      DESIGN: Following institutional review board approval, 28 women presenting with
      cytological atypical glandular cells underwent repeat thin-prep cytology, Hybrid
      Capture 2 human papilloma virus DNA testing, colposcopic evaluation, Fisher
      electrosurgical conization, and endometrial sampling. Human papilloma virus test
      results in each patient were then correlated with histologic lesions, if present.
      RESULTS: Sixteen of the 28 study patients had pathologic lesions (11/28 high
      grade squamous intraepithelial lesion, 3/28 low-grade squamous intraepithelial
      lesion, 1/28 adenocarcinoma in situ, 1/28 simple endometrial hyperplasia). Human
      papilloma virus DNA testing was available in 24 of 28 subjects (86%). The
      sensitivity of human papilloma virus positivity to predict the presence of
      cervical intraepithelial neoplasia was 100% (confidence interval 77% to 100%),
      specificity 64% (confidence interval 35% to 85%), positive predictive value 76%,
      and negative predictive value 100%. Women who tested human papilloma virus
      positive were 12 times more likely to have cervical intraepithelial neoplasia
      than women who were human papilloma virus negative (Fisher P<.001). Human
      papilloma virus positivity was not predictive of endometrial pathology; women who
      were human papilloma virus positive were less likely to have endometrial
      pathology than were women who were human papilloma virus negative (risk ratio
      1.6, 95% confidence interval 0.01-1.7). CONCLUSION: Atypical glandular cells can
      represent a variety of lesions. The majority of the lesions will be squamous
      intraepithelial lesions of the cervix (50%), with high-grade squamous
      intraepithelial lesion present in 40% of subjects. Human papilloma virus DNA
      testing is a sensitive test for the presence of squamous intraepithelial lesion,
      with excellent negative predictive value for the absence of squamous
      intraepithelial lesion. The results of this study suggest human papilloma virus
      DNA testing might be an effective screening test in the initial evaluation and
      management of cytological atypical glandular cells.

PMID- 16098898
TI  - Predictors of suboptimal surgical cytoreduction in women treated with initial
      cytoreductive surgery for advanced stage epithelial ovarian cancer.
AB  - OBJECTIVE: The purpose of this study was to determine if a suboptimal
      cytoreduction can be predicted preoperatively in women with advanced ovarian
      cancer. STUDY DESIGN: All women with stage III/IV epithelial ovarian cancer
      treated with initial surgery at our hospital between January 1, 1995 and January
      1, 2003 were eligible; 56 patients met inclusion criteria and underwent
      retrospective chart review. Statistical analysis was performed using SPSS.
      RESULTS: Twenty-nine women (52%) had optimal cytoreduction (OC), and 27 (48%) had
      suboptimal cytoreduction (SC). Women in the SC group had higher median CA-125
      values at surgery (954 SC vs 597 OC, P = .07). Three sites of disease on
      preoperative CT were reported more frequently in the SC patients; omentum (P =
      .007), parietal peritoneum (P = .096), and ascites (P = .093). CONCLUSION: A
      suboptimal cytoreduction confers no survival advantage to women with advanced
      ovarian cancer. Thus, these patients may be the best candidates for initial
      chemotherapy, and identifying them preoperatively becomes important.

PMID- 16098901
TI  - Upper vaginectomy for the treatment of vaginal intraepithelial neoplasia.
AB  - OBJECTIVE: The purpose of this study was to evaluate the use of upper vaginectomy
      for the treatment of vaginal intraepithelial neoplasia (VAIN). STUDY DESIGN: We
      conducted a retrospective review. Between August 1, 1985 and April 30, 2004, 105
      patients were identified who had undergone upper vaginectomy for VAIN. RESULTS:
      Thirty-six patients had previously been treated for VAIN. Mean operative time and
      estimated blood loss were 55 minutes and 113 mL, respectively. Ten percent had
      intraoperative complications. Twenty-three (22%) patients had negative findings
      on final pathologic examination, and invasive cancer was found in 13 (12%)
      patients. Four patients had postoperative complications. Follow-up was available
      in 52 patients; 46 (88%) remain without recurrence at a mean follow-up of 25
      months. CONCLUSION: In our patients, upper vaginectomy was efficacious for the
      treatment of VAIN. The procedure led to the diagnosis of occult invasive cancer
      in 12% of these women.

PMID- 16098905
TI  - Is early embryonic crowding responsible for premature delivery and low birth
      weight of singleton pregnancies conceived by assisted reproductive technology?

PMID- 16098902
TI  - Sites of bowel resected to achieve optimal ovarian cancer cytoreduction:
      implications regarding surgical management.
AB  - OBJECTIVE: The purpose of this study was to 1) report on the distribution of
      bowel segments resected in a population of patients who underwent primary optimal
      cytoreductive surgery for epithelial ovarian cancer, and 2) discuss implications
      for surgical management regarding resection of these bowel segments. STUDY
      DESIGN: This was a retrospective study from 1995 to 2003 of 144 ovarian cancer
      patients who underwent primary optimal cytoreductive operations that included
      bowel resection. RESULTS: Bowel segments removed and major complications are
      presented in tabulated form. Eighty-one out of 144 resections were rectosigmoid
      only. Thirty-six percent had extensive involvement of colon segments separate
      from the rectosigmoid. Excluding hemorrhage, 9 patients (6%) experienced a major
      complication. CONCLUSION: The present study does suggest the necessity for a
      highly individualized approach to the surgical management of epithelial ovarian
      cancer patients who can be optimally cyto-reduced by resection of multifocal
      colonic involvement. Further study is needed to better assess the complications,
      function, and oncologic outcome of the different surgical approaches to these
      patients.

PMID- 16098909
TI  - First-trimester crown-rump-length (CRL) discrepancy: much ado about nothing?

PMID- 16098908
TI  - Condoms and reproductive health.

PMID- 16098911
TI  - Impact of endometrioma resection prior to IVF/ICSI cycles.

PMID- 16098913
TI  - Spindlin1, a novel nuclear protein with a role in the transformation of NIH3T3
      cells.
AB  - spindlin1, a novel human gene recently isolated by our laboratory, is highly
      homologous to mouse spindlin gene. In this study, we cloned cDNA full-length of
      this novel gene and send it to GenBank database as spindlin1 (Homo sapiens
      spindlin1) with Accession No. AF317228. In order to investigate the function of
      spindlin1, we studied further the subcellular localization of Spindlin1 protein
      and the effects of spindlin1 overexpression in NIH3T3 cells. The results showed
      that the fusion protein pEGFP-N1-spindlin1 was located in the nucleus and the C
      terminal is correlated with nuclear localization of Spindlin1 protein. NIH3T3
      cells which could stably express spindlin1 as a result of RT-PCR analysis
      compared with the control cells displayed a complete morphological change; made
      cell growth faster; and increased the percentage of cells in G2/M and S phase.
      Furthermore, overexpressed spindlin1 cells formed colonies in soft agar in vitro
      and formed tumors in nude mice. Our findings provide direct evidence that
      spindlin1 gene may contribute to tumorigenesis.

PMID- 16098914
TI  - Impaired repressor activity and biological functions of PU.1 in MEL cells induced
      by mutations in the acetylation motifs within the ETS domain.
AB  - PU.1, a hematopoietic Ets transcription factor, is required for development of
      the lymphoid and myeloid lineages. We have previously shown that PU.1 functions
      as both a transcriptional activator and repressor through complex formation with
      CBP/p300 and HDAC1/mSin3A/MeCP2, respectively. To determine whether modification
      of PU.1 is responsible for switching its association between co-activators and co
      repressors, we examined whether acetylation regulates the physical and functional
      activities of PU.1. PU.1 was acetylated in vivo and its repressor activity was
      reduced when the putative acetylation motifs in the Ets domain were mutated. The
      mutant cooperated with CBP similar to wild type PU.1, but insufficiently with
      GATA-1 and mSin3A. Whereas overexpression of wild type PU.1 induced
      differentiation block, growth inhibition, and apoptotic cell death in MEL
      erythroleukemia cells as we reported previously, overexpression of the mutant
      acetylation motif PU.1 did not. Taken together, our data suggest that acetylation
      might regulate the biological functions of PU.1 in erythroid cells.

PMID- 16098916
TI  - Hepatic insulin resistance induced by chronic hindlimb ischemia.
AB  - Peripheral vascular disease (PVD) has been reported to cause deterioration in
      insulin sensitivity. The precise mechanism of insulin resistance induced by PVD
      has not been clarified. To elucidate the mechanism causing impaired insulin
      action and glucose metabolism under peripheral ischemic conditions, we determined
      glucose turnover and glucose tolerance in hindlimb-ischemic (FAL) rats. The right
      femoral artery was ligated in hindlimb-ischemic (FAL) rats, while the artery was
      only exposed in the Sham operated (Sham) rats used as a control. Two weeks after
      the ligation, glucose tolerance was impaired and plasma insulin levels were
      significantly increased in FAL rats compared with Sham rats after intraperitoneal
      glucose loading (2 g kg(-1)). Under euglycemic hyperinsulinemic clamp conditions,
      the glucose infusion rate was significantly lower in FAL rats compared with Sham
      rats, but there was no significant difference in the glucose disappearance rate
      between the two groups. Hyperinsulinemia suppressed endogenous glucose production
      by 50% in Sham rats, while the suppression was 20% in FAL rats, indicating
      hepatic insulin resistance in FAL rats. mRNA analysis of isolated liver after the
      clamp experiment revealed that glucokinase mRNA, but not PEPCK and glucose-6
      phosphatase mRNA, was significantly lower in FAL rats compared with Sham rats. In
      conclusion, chronic hindlimb ischemia impaired glucose tolerance associated with
      insulin resistance in the liver rather than the peripheral tissues.

PMID- 16098915
TI  - Lib, transcriptionally induced in senile plaque-associated astrocytes, promotes
      glial migration through extracellular matrix.
AB  - In an effort to identify astrocyte-derived molecules that may be intimately
      associated with progression of Alzheimer's disease (AD), Lib, a type I
      transmembrane protein belonging to leucine-rich repeat superfamily, has been
      identified as a distinctly inducible gene, responsive to beta-amyloid as well as
      pro-inflammatory cytokines in astrocytes. To evaluate the roles of Lib in AD, we
      investigated Lib expression in AD brain. In non-AD brain, Lib mRNA has been
      detected in neurons but not in quiescent astrocytes. On the contrary, in AD
      brain, Lib mRNA is expressed in activated astrocytes associated with senile
      plaques, but not expressed in neurons around lesions. Lib-expressing glioma cells
      displayed promotion of migration ability through reconstituted extracellular
      matrix and recombinant Lib protein bound to constituents of extracellular matrix.
      These observations suggest that Lib may contribute to regulation of cell-matrix
      adhesion interactions with respect to astrocyte recruitment around senile plaques
      in AD brain.

PMID- 16098917
TI  - ATP enhances exocytosis of insulin secretory granules in pancreatic islets under
      Ca2+-depleted condition.
AB  - Glucose and other nutrients have been shown to stimulate insulin release from
      pancreatic islets under Ca2+-depleted condition when protein kinase A (PKA) and
      protein kinase C (PKC) are activated simultaneously. We investigated the role of
      metabolic nucleotide signals including ATP, ADP, and GTP in exocytosis of insulin
      secretory granules under Ca2+-depleted condition using electrically permeabilized
      rat islets. ATP under PKC activation augmented insulin release concentration
      dependently by 100 nM 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in Ca2+
      depleted condition, while ADP could not suppress ATP-dependent insulin release in
      this condition. Neither GTP nor activated PKA in the absence of PKC activation
      increased insulin release under Ca2+-depleted condition in the presence of ATP,
      but both enhanced insulin secretion in the presence of ATP when PKC was
      activated. In conclusion, activated PKC and the presence of ATP both are required
      in the insulin secretory process under Ca2+-depleted condition. While PKA
      activation and GTP cannot substitute for PKC activation and ATP, respectively,
      under Ca2+-depleted condition, they enhance ATP-dependent insulin secretion when
      PKC is activated.

PMID- 16098918
TI  - Cameroon local diet-induced glucose intolerance and dyslipidemia in adult Wistar
      rat.
AB  - It has been hypothesised that glucose intolerance or diabetes can be induced in
      rodents by a hypercaloric-fat diet or a hypercaloric-sucrose diet. This study was
      designed to examine the effects of a high-fat diet (HFD: carbohydrates 35-40%
      kcal, fat 50-55% kcal, protein 10-15% kcal) and a high-sucrose diet (HSD:
      carbohydrates 65-70% kcal, fat 25-30% kcal, protein 10-15% kcal) compared to a
      normal or standard diet (ND: carbohydrates 50-55% kcal, fat 15-20% kcal, protein
      25-30% kcal) on fasting plasma glucose, glucose tolerance test, plasma
      triglycerides, plasma cholesterol, body weight, food and water consumption in
      male Wistar rats. After 4 months, weight gain, plasma triglycerides level,
      fasting plasma glucose and water intake were significantly elevated (p<0.05) in
      all test groups when compared to the control group. Total HDL and LDL cholesterol
      levels were significantly elevated (p<0.05) in the HFD group, whereas the HDL
      level was significantly lower in the HSD group associated with an atherogenic
      index significantly elevated (p<0.05) when compared to the control group. After
      16 weeks of dietary treatment, an oral glucose tolerance test (OGTT) showed a
      significant increase in plasma glucose levels after 2-4 h of glucose challenge in
      all test groups. During the experiment, it was noticed that important weight gain
      observed in all dietary test groups was associated with a significant low
      (p<0.05) food consumption. The above results suggest that dietary nutrients
      contained in these hypercaloric diets might have an effect on insulin action and
      therefore, might contribute to the development of glucose intolerance and type 2
      diabetes. These results also suggest that, in addition to their diabetogenic
      effect, these hypercaloric diets might probably have an atherogenic effect and
      could be use in a long-term study to induce type 2 (non-insulino-dependant)
      diabetes mellitus.

PMID- 16098920
TI  - Clinical features of non-diabetic renal diseases in patients with type 2
      diabetes.
AB  - Although persistent proteinuria is characteristic of diabetic nephropathy (DN),
      it is important to differentiate non-diabetic renal diseases (NDRD) in diabetic
      patients with proteinuria. In order to re-evaluate the indications for renal
      biopsy in the diabetic patients, we retrospectively analyzed the relationship
      between clinical features and histological diagnosis in 97 Japanese patients with
      type 2 diabetes manifesting overt proteinuria. Renal biopsy was performed because
      they were clinically suspected to have NDRD. Patients were divided into three
      groups according to the histological diagnosis: (1) the DN group (n=35) had only
      diabetic lesions, (2) the complicated group (n=16) had histological changes of
      NDRD superimposed on DN and (3) the non-DN group (n=46) had NDRD without diabetic
      lesions. We evaluated the specificity and sensitivity of four clinical parameters
      (duration of diabetes, presence or absence of diabetic retinopathy, microscopic
      hematuria and granular casts as urinary sediments) for the prediction of NDRD.
      Short duration of diabetes (<5 years) showed high sensitivity (75%) and
      specificity (70%). Diabetic retinopathy showed the highest sensitivity (87%) and
      specificity (93%). The sensitivity and specificity of microscopic hematuria (56
      and 58%) and granular casts (68 and 47%) were lower. Our study confirmed that the
      absence of retinopathy and short duration of diabetes are useful clinical
      indications for renal biopsy in diabetic patients with overt proteinuria.

PMID- 16098919
TI  - IL-15 is elevated in serum patients with type 1 diabetes mellitus.
AB  - IL-15 is a 14-15 kD cytokine produced by monocytes/macrophages and shares some
      biological actions with IL-2. The serum concentration of IL-15 in type 1 diabetic
      patients has not been reported seriously. Our studies were performed on 51
      patients (28 women and 23 men) with type 1 diabetes mellitus. Healthy control
      subjects (n=22, 12 women and 10 men, mean age 29 years, range 24-32 years) were
      recruited from medical staff. IL-15 serum levels were detected by ELISA (R & D
      systems, USA). Short-term and long-term metabolic control parameters, lipid
      profile and C-reactive protein levels were also estimated. There was a
      statistically significant increase of serum IL-15 in type 1 diabetic patients in
      comparison to the control subjects (4.4 (1.5-11.8) versus 2.9 (1.5-6.0) pg/ml,
      p<0.05). Diabetic patients with higher IL-15 serum levels had higher HbA1c
      values. A correlation was found between IL-15 serum concentration and HbA1c
      (N(s)=0.31, p=0.029). There was no relation between acute hyperglycaemic episodes
      and IL-15 serum level. The potential associations between IL-15 serum level and
      long-term diabetic control lead us to speculate that IL-15 may serve as a target
      for future treatment in patients with prediabetes and/or for prevention of late
      diabetic complications.

PMID- 16098921
TI  - Increased erythropoiesis and subclinical inflammation as part of the metabolic
      syndrome.
AB  - Recent studies have suggested the insulin resistance might be accompanied by
      enhanced erythropoiesis. We have examined this association in individuals with
      the metabolic syndrome (MS) who in addition to insulin resistance harbor a
      chronic low grade inflammation. This study is relevant because chronic
      inflammation might have a suppressive effect on erythropoiesis. 280 and 554 non
      smoking women and men with respective age of 46.4+/-9.3 (mean+/-S.D.) and 44.0+/
      11.0 years are included. A significant correlation was noted between the numbers
      of the components of the MS and the inflammatory biomarkers including the white
      blood cell count, high sensitivity C-reactive protein, fibrinogen concentrations
      and the erythrocyte sedimentation rate. In addition, a significant correlation
      (r=0.157, p=0.008) was noted between the number of components of the MS and the
      number of red blood cells in the peripheral blood in women. The same was true for
      men (r=0.192, p<0.0005). We conclude that enhanced erythropoiesis could be a new,
      hitherto unrecognized component of the MS. The enhanced erythropoiesis could give
      an erroneous impression of general "good" health in these individuals.

PMID- 16098922
TI  - Hospital admission for selected single virus infections prior to diabetes
      mellitus.
AB  - AIMS: To determine whether hospital admission for a range of specified virus
      infections was followed by a raised admission rate for diabetes mellitus; and, if
      raised, whether the increase is compatible with the hypothesis that virus
      infection is a cause of diabetes. METHODS: Analysis of a database of hospital
      statistics including admissions for people with diabetes mellitus before the age
      of 30 years. RESULTS: There was no evidence of excess risk of diabetes after
      measles, mumps, rubella, infectious mononucleosis, influenza, infectious
      hepatitis, varicella and herpes zoster, herpes simplex, aseptic meningitis or
      bronchiolitis. For example, of 1433 patients admitted for measles, 6 were later
      admitted with diabetes (risk ratio 1.32; 95% confidence interval 0.5-2.9); of 866
      patients admitted for mumps, 2 were later admitted for diabetes (risk ratio 0.74;
      0.1-2.7). Numbers of people with diabetes subsequent to infection were too few,
      however, to rule out the possibility of small effects. CONCLUSIONS: Our findings
      do not support the hypothesis that any of these virus infections initiate the
      processes that lead to the development of diabetes, or that these infections act
      as a trigger to precipitate active disease in those whose diabetes is already
      present but latent.

PMID- 16098923
TI  - Associations of microalbuminuria and blood pressure with carotid, aortic and
      femoral atheromatous plaques in elderly Finns.
AB  - AIMS: To evaluate the possible associations of microalbuminuria (MA) and blood
      pressure (BP) with the ultrasonographic manifestations of carotid, aortic and
      femoral atherosclerosis in 65-year-old Finns. METHODS: Ultrasonographic
      measurements were performed on 54 diabetic subjects, 97 subjects with impaired
      glucose tolerance (IGT) and 57 normoglycemic subjects (NGT). Urinary albumin and
      creatinine concentrations were measured from an early morning spot urine sample,
      and the urinary albumin-to-creatinine ratio (ACR) of > or = 2.5 mg/mmol in men
      and > or = 3.5 mg/mmol in women was used as a measure of MA. Hypertension was
      defined as either a systolic BP of > or = 160 mmHg or a diastolic BP of > or = 95
      mmHg or being on antihypertensive medication. RESULTS: Eighteen subjects were
      microalbuminuric and 176 subjects normoalbuminuric. MA was associated with
      diabetes mellitus and high systolic and diastolic BP. The subjects were divided
      into two groups according to the median total number of carotid, aortic and
      femoral plaques: > or = 9 versus 0-8 plaques. A high number of plaques were
      associated with hypertension, male gender, smoking and MA. When the study
      subjects were stratified according to hypertension, it turned out that MA was
      associated with a high number of plaques in hypertensive, but not in
      nonhypertensive subjects. According to the results of logistic regression
      analysis with a high number of plaques as the dependent variable, the unadjusted
      OR for smoking was 6.0 (95% CI 2.4-15.3) in hypertensive subjects.
      Microalbuminuria was of borderline statistical significance (OR 4.5, 95% CI 0.9
      22.9). After adjustment for systolic blood pressure and fasting glucose
      concentration, the OR for microalbuminuria was reduced to 3.3 (95% CI 0.6-18.4).

PMID- 16098924
TI  - N-(carboxymethyl)valine residues in hemoglobin (CMV-Hb) reflect accumulation of
      oxidative stress in diabetic patients.
AB  - While carboxymethylated proteins are considered to be advanced glycation end
      products (AGE), they can also be induced by reactive oxygen species (ROS)
      independently of the AGE-forming process. To clarify whether N
      (carboxymethyl)valine residues in hemoglobin (CMV-Hb) were a useful marker of the
      accumulation of ROS in diabetes, we evaluated CMV-Hb formation in vitro and in
      vivo. For the in vitro studying, purified human hemoglobin was incubated with D
      glucose or D-glucose and hydrogen peroxide. For the in vivo study, CMV-Hb was
      extracted from peripheral red blood cells in diabetic patients and compared with
      that from non-diabetic subjects. Furthermore, the effect of antioxidants was
      evaluated after 6 months in 15 diabetic patients showing very high CMV-Hb levels.
      In vitro CMV-Hb formation increased in a glucose concentration and time-dependent
      manner. Co-incubation with glucose and hydrogen peroxide synergistically
      increased CMV-Hb formation. The CMV-Hb level was higher in the diabetic group
      than the non-diabetic group, and CMV-Hb was correlated with the plasma total
      cholesterol and serum creatinine levels. The CMV-Hb level was decreased by
      antioxidant therapy, whereas HbA1c did not change. These results demonstrate that
      CMV-Hb may be a useful marker for accumulation of oxidative stress in diabetic
      patients.

PMID- 16098925
TI  - Gestational diabetes in Iran: incidence, risk factors and pregnancy outcomes.
AB  - The objective of this study was to determine the incidence of gestational
      diabetes mellitus (GDM) and compare fetal, maternal and neonatal complications
      amongst women with GDM and pregnant women with normal glucose tolerance in an
      urban Iranian population. In a prospective cohort study, universal screening for
      gestational diabetes mellitus was performed for 1310 pregnant women who were
      referred from private clinics and community health care centers to Fatemiyeh
      Hospital in Shahrood City. Screening was performed with a 50 g oral Glucose
      Challenge Test (GCT) with 130 mg/dl cut-off point, then a diagnostic 100 g Oral
      Glucose Tolerance Test (OGTT) was done according to Carpenter and Coustan
      criteria. The incidence of GDM was 4.8%. There were differences in risk factors:
      age >30 years, family history of diabetes, obesity, previous macrosomia,
      glycosuria between the two groups (P<0.001). Women with GDM had a higher rate of
      stillbirth (P<0.001; odds ratio 17.1, 95% CI=4.5-65.5), hydramnios (P<0.001; odds
      ratio 15.5, 95% CI=4.8-50.5), gestational hypertension (P<0.001; odds ratio 6,
      95% CI=2.3-15.3), macrosomia (P<0.05; odds ratio 3.2, 95% CI=1.2-8.6) and
      caesarean section (P<0.001). We have found that the incidence of GDM in an urban
      Iranian population is similar to developed countries. Complications were more
      common in the GDM group than in the normal group and outcomes for women with
      persistent diabetes post-partum were particularly poor. We recommend screening
      for GDM in Iran, but further evaluation of selective screening and cost
      effectiveness will need to be performed. Measures to improve the outcome of GDM
      pregnancy will also need to be addressed in the future.

PMID- 16098927
TI  - Diabetes worsens the outcome of acute ischemic stroke.
AB  - OBJECTIVE: To characterize acute stroke events in diabetic patients in a
      population-based stroke register and to determine the influence of diabetes on
      the outcome of acute stroke. METHODS: Four thousand three hundred and ninety
      patients were recorded in the FINMONICA and FINSTROKE registers after their first
      ischemic stroke from 1990 to 1998. We followed mortality and stroke outcome for
      up to 4 weeks after the onset of acute stroke. RESULTS: Of the 4390 patients who
      had had an ischemic stroke, 43.6% were male and 25.1% (1103) had diabetes. Their
      mean age was 72.4 (S.D. 12.0) years and this was similar in patients with and
      without diabetes (72.9 years versus 72.3 years, p=0.18). Subjects with diabetes
      were more likely to be hypertensive (55% versus 38%, p<0.001) and have a history
      of myocardial infarction (20% versus 16%, p<0.001) than the non-diabetic stroke
      patients. Mortality at 4 weeks from the onset was higher in diabetic than in non
      diabetic patients (20.0% versus 16.9% p=0.020). At day 28 after the stroke
      attack, diabetic patients were more likely to be disabled when compared with non
      diabetic subjects (43.3% versus 33.5%, p<0.001). Using logistic regression
      analysis, adjusted for age-group, sex, previous medical history (MI, AF or TIA),
      diabetes was found to be a significant predictor of disability after stroke
      (OR=1.51, 95% CI 1.27-1.81). CONCLUSIONS: Diabetes, which affected one-fourth of
      the ischemic stroke patients on our register, was associated with a higher risk
      of death and disability after the onset of stroke. Preventing diabetes in the
      elderly population improves the short-term prognosis of acute ischemic stroke.

PMID- 16098926
TI  - WRN gene 1367 Arg allele protects against development of type 2 diabetes
      mellitus.
AB  - Werner's syndrome is an autosomal recessive disease caused by mutation of the WRN
      gene, which may lead to DNA repair failure and acceleration of aging. A
      polymorphism at amino acid 1367 Cys (TTG)/Arg (CTG) reportedly reduces the risk
      of myocardial infarction in Japanese. We studied the possible involvement of this
      polymorphism in type 2 diabetes. When polymorphism of the WRN gene was analyzed
      in 272 randomly recruited type 2 diabetic subjects (age 64.5+/-11.1), we found
      those with Cys/Arg to be older than those with Cys/Cys (p=0.021) and that the age
      at diagnosis of diabetes was greater in Cys/Arg than in Cys/Cys subjects
      (p=0.011). Diabetes-free survival rate over the age, analyzed by Kaplan-Meier
      method, differed significantly between these two genotype groups (p=0.0125) and
      the survival curve was shifted to the right in the Cys/Arg group as compared to
      the Cys/Cys group. No difference in allele frequency was observed between our
      diabetic (n=272) and non-diabetic subjects (n=171, age 66.0+/-8.0). These results
      suggest that the 1367 Arg allele of the WRN gene protects against the development
      of type 2 diabetes mellitus in Japanese.

PMID- 16098928
TI  - A case of type 2 diabetes with a large abscess of the gastric wall successfully
      treated with a glycemic control and systemic antibiotics.
AB  - A case of type 2 diabetic patient, a 67-year-old woman, with a large abscess of
      the gastric wall which seemed to be a primary lesion is described for the first
      time. Fortunately, patient was successfully treated with both the maintenance of
      a good glycemic control and systemic antibiotics without laparotomy or drainage.
      Thus, a tight glycemic control and awareness of this disease should be
      reemphasized, and this may improve the prognosis of this rare and fatal one, even
      a poorly-controlled diabetes.

PMID- 16098929
TI  - Pioglitazone prevents reactive hypoglycemia in impaired glucose tolerance.
AB  - A 42-year-old woman with hypoglycemic symptoms that occurred several hours after
      a meal visited our hospital. The hypoglycemic symptoms appeared when she was 37
      years old, and her plasma glucose level had been assessed as less than 60 mg/dL
      when she experienced the symptoms. One year before, she had been diagnosed with
      reactive hypoglycemia by 75 g-oral glucose tolerance test (OGTT), which showed a
      normal glucose tolerance (NGT) pattern, and had begun taking an alpha-glucosidase
      inhibitor and nutritional treatment. A 75 g-OGTT on admission showed hypoglycemia
      at 240 min after glucose loading, excessive insulin secretion and an impaired
      glucose tolerance (IGT) pattern. A euglycemic-hyperinsulinemic clamp study
      demonstrated decreased insulin sensitivity. Therefore, we suspected that she had
      reactive hypoglycemia associated with insulin resistance and treated her with 15
      mg/day pioglitazone. Her hypoglycemic symptoms completely disappeared after
      treatment with pioglitazone; insulin sensitivity in a euglycemic-hyperinsulinemic
      clamp study improved. Another 75 g-OGTT revealed that the excessive insulin
      secretion and hypoglycemia at 240 min after glucose loading had disappeared, and
      glucose tolerance was normalized from an IGT pattern to an NGT pattern. Thus, we
      believe that pioglitazone is effective for reactive hypoglycemia and aggravated
      glycemic metabolism associated with insulin resistance.

PMID- 16098930
TI  - Paradigm lost, paradigm found: the re-emergence of hormesis as a fundamental dose
      response model in the toxicological sciences.
AB  - This paper provides an assessment of the toxicological basis of the hormetic dose
      response relationship including issues relating to its reproducibility,
      frequency, and generalizability across biological models, endpoints measured and
      chemical class/physical stressors and implications for risk assessment. The
      quantitative features of the hormetic dose response are described and placed
      within toxicological context that considers study design, temporal assessment,
      mechanism, and experimental model/population heterogeneity. Particular emphasis
      is placed on an historical evaluation of why the field of toxicology rejected
      hormesis in favor of dose response models such as the threshold model for
      assessing non-carcinogens and linear no threshold (LNT) models for assessing
      carcinogens. The paper argues that such decisions were principally based on
      complex historical factors that emerged from the intense and protracted conflict
      between what is now called traditional medicine and homeopathy and the overly
      dominating influence of regulatory agencies on the toxicological intellectual
      agenda. Such regulatory agency influence emphasized hazard/risk assessment goals
      such as the derivation of no observed adverse effect levels (NOAELs) and the
      lowest observed adverse effect levels (LOAELs) which were derived principally
      from high dose studies using few doses, a feature which restricted perceptions
      and distorted judgments of several generations of toxicologists concerning the
      nature of the dose-response continuum. Such historical and technical blind spots
      lead the field of toxicology to not only reject an established dose-response
      model (hormesis), but also the model that was more common and fundamental than
      those that the field accepted.

PMID- 16098932
TI  - Endovascular repair of thoracic and abdominal aortic aneurysms: pre- and
      postprocedural imaging.
AB  - Endovascular repair of thoracic and abdominal aortic aneurysms is a safe
      alternative to conventional open surgical repair. Clinical success, however, is
      highly dependent on patient selection. Diagnostic vascular imaging has an
      essential role for this selection process. Following endovascular aneurysm repair
      (EVAR), patients require long-term surveillance and again vascular imaging serves
      an integral function. This article reviews EVAR selection criteria and post-EVAR
      assessment and then discusses the imaging modalities used to evaluate these
      patients, namely multi-detector-row computed tomographic angiography, magnetic
      resonance imaging/angiography, duplex ultrasonography, and catheter angiography.

PMID- 16098933
TI  - Past, present, and future endograft devices.
AB  - Since the original descriptions of endovascular grafts for treatment of
      aneurysms, a number of devices and approaches have been developed. The following
      is a discussion summarizing the number of devices which have been developed and
      used in patients, as well as chosen the directions of this technology. The
      diversity of approach from an engineering and materials point of view speaks of
      the fact that opportunity exists for continued development in the future.

PMID- 16098934
TI  - Complications and bail-out situations during AAA endovascular repair.
AB  - The endovascular stent-graft is now a universally accepted treatment for
      abdominal aortic aneurysms but remains nonetheless experimental. There are
      generic aspects of endograft insertion as well as device specific deployment
      issues. There are a number of potential procedural complications, related to
      vascular access and to the deployment sequence. The common technical problems are
      described and, where possible, the endovascular solutions are outlined.

PMID- 16098935
TI  - Delayed complications following EVAR.
AB  - More than a decade after the first clinical attempts, two large randomized
      studies have proven that endovascular aortic aneurysm repair (EVAR) provides
      immediate advantages over open repair. In the long run, however, a relatively
      high number of reinterventions is necessary to improve the long-term efficacy of
      EVAR, which may outweigh the early benefits. Since EVAR is gaining popularity in
      the medical community and in patients with abdominal aortic aneurysm (AAA), it is
      expected that a growing number of patients will present with delayed
      complications requiring some kind of reinterventions. For the patient's safety,
      vascular surgeons and interventional radiologists involved in EVAR must be well
      aware of these complications and the ways to overcome them. We began our
      endovascular program for AAA in 1994 and currently follow 485 patients with a
      variety of manufactured grafts. In this article we describe the delayed
      complications observed with EVAR, their mechanisms, favoring factors, and ways to
      treat them.

PMID- 16098936
TI  - Endoleak: treatment options.
AB  - Endoleak, also called leakage, leak, and Perigraft leak, is a major complication
      and its persistence represents a failure of endovascular aortic aneurysm repair
      (EVAR). Its detection and treatment is therefore of primary importance since
      endoleak is associated with pressurization (increases pressure) of the sac,
      resulting in expansion and rupture of the aneurysm. The aim of this article was
      to discuss the different options to treat endoleak.

PMID- 16098937
TI  - Introduction to biomechanics related to endovascular repair of abdominal aortic
      aneurysm.
AB  - Biomechanical issues of practical relevance to the physician in the clinical
      management of patients undergoing endovascular repair (EVR) of their abdominal
      aortic aneurysms (AAA) is discussed. Following a brief description of key terms
      in vascular biomechanics, background on the current state of knowledge in the
      biomechanics of AAA pathogenesis and rupture is provided. This is followed by a
      discussion of key issues of biomechanical relevance in EVR such as the mechanics
      of endotension, the notion of intraaneurysmal sac pressure and potential pitfalls
      of techniques used to measure them, mechanics of graft fracture/kinking, and
      graft migration. The discussions are intended to provide an overview of this
      field to physicians.

PMID- 16098938
TI  - Branched stent-grafts for endovascular repair of aortic and iliac aneurysms.
AB  - Endovascular technique, which gains access through indirect transarterial routes
      and isolates the aneurysm without interrupting flow, has particular advantages in
      aneurysms of the aortic arch and thoracoabdominal aorta. Yet progress has been
      slow. The necessary branched stent-grafts face several unique technical
      challenges. The simplest, most versatile approach involves assembling a modular
      stent-graft in situ from multiple parts. Techniques vary according to the
      presence or absence of an overlap zone, or cuff. The first cases of this type,
      reported over 4 years ago, had axially oriented cuffs. Recent efforts have seen
      the intercomponent attachment site reduced to a ring of Nitinol around a simple
      fenestration, with various hybrids of cuffed and fenestrated technique in
      between. Other advances, such as better sheaths, better covered stents, and
      commercial manufacture (Cook, Australia), have helped to extend the use of
      branched stent-grafts to a wider range of users and a wider range of aneurysms.
      Although their future role remains unclear, all these devices have gone beyond
      the proof of concept stage, and some, such as the bifurcated component for the
      endovascular iliac reconstruction, are ready to become standard parts of the
      endovascular.

PMID- 16098939
TI  - Stent-graft repair of thoracic aortic aneurysms.
AB  - Endovascular treatment of aortic disease has emerged as an alternative mode of
      treatment that is particularly attractive for patients with severe comorbidities
      who would not be ideal candidates for open surgery. Actually, short-term
      morbidity and mortality rates, of large series, compare favorably with those from
      surgery, and stent-graft placement is proving to be a safe, minimally invasive,
      and effective treatment for thoracic aortic diseases. However, although
      endoluminal interventions are minimally invasive, they are associated with
      complications, as are surgical methods. In this article, indications, technical
      aspects, and results of endovascular TAA repairs will be reviewed. We will also
      examine the advantages and limitations of stent-graft treatment. Finally, we will
      discuss the management of complications following aortic stent-graft
      implantation. We intentionally do not cover the topic of thoracic dissection, as
      it is being covered in another article in this volume.

PMID- 16098940
TI  - Beyond competition: a new paradigm for collaborative cardiovascular research in
      Australia.

PMID- 16098941
TI  - Developing clinical knowledge through a narrative-based method of interpretation.
AB  - The results of research using a narrative analysis provide new clinical
      knowledge, but the methods used are unknown to many readers. In this paper we
      present an example of how an analysis may be performed in practice. The purpose
      of the interpretation of this specific story was to develop clinical knowledge of
      how it is to live with chronic heart failure from a daily life perspective. The
      steps in the interpretation process, within the framework of Paul Ricoeur's
      Interpretation theory, were: (1) general or naive reading, (2) distancing, (3)
      examination of discourse, (4) conjectures and questions, and (5) reflection over
      the whole. The demonstrated interpretation of the interview resulted in a theme
      called: "Struggling to comprehend medical information". This systematic way of
      working with narratives makes implicit assumptions about the relationship between
      meaning and language explicit. These themes can be used in everyday practice as
      clinical tools. Because of the interpretative nature of human understanding the
      experienced health professional will be capable of integrating evidence-based
      research findings and individual illness experience.

PMID- 16098942
TI  - Oscillatory motion induces change blindness.
AB  - Change blindness is the relative inability of normally sighted observers to
      detect large changes in scenes when the low-level signals associated with those
      changes are either masked or of extremely low magnitude. Change detection can be
      inhibited by saccadic eye movements, artificial saccades or blinks, and 'mud
      splashes'. We now show that change detection is also inhibited by whole image
      motion in the form of sinusoidal oscillations. The degree of disruption depends
      upon the frequency of oscillation, which at 3 Hz is equivalent to that produced
      by artificial blinks. Image motion causes the retinal image to be blurred and
      this is known to affect object recognition. However, our results are inconsistent
      with good change detection followed by a delay due to poor recognition of the
      changing object. Oscillatory motion can induce eye movements that potentially
      mask or inhibit the low-level signals related to changes in the scene, but we
      show that eye movements promote rather than inhibit change detection when the
      image is moving.

PMID- 16098943
TI  - Models of high-dimensional semantic space predict language-mediated eye movements
      in the visual world.
AB  - In the visual world paradigm, participants are more likely to fixate a visual
      referent that has some semantic relationship with a heard word, than they are to
      fixate an unrelated referent [Cooper, R. M. (1974). The control of eye fixation
      by the meaning of spoken language. A new methodology for the real-time
      investigation of speech perception, memory, and language processing. Cognitive
      Psychology, 6, 813-839]. Here, this method is used to examine the psychological
      validity of models of high-dimensional semantic space. The data strongly suggest
      that these corpus-based measures of word semantics predict fixation behavior in
      the visual world and provide further evidence that language-mediated eye
      movements to objects in the concurrent visual environment are driven by semantic
      similarity rather than all-or-none categorical knowledge. The data suggest that
      the visual world paradigm can, together with other methodologies, converge on the
      evidence that may help adjudicate between different theoretical accounts of the
      psychological semantics.

PMID- 16098944
TI  - Does an auditory distractor sequence affect self-paced tapping?
AB  - This study investigated whether an auditory distractor (D) sequence affects the
      timing of self-paced finger tapping. To begin with, Experiment 1 replicated
      earlier findings by showing that, when taps are synchronized with an isochronous
      auditory target (T) sequence, an isochronous D sequence of different tempo and
      pitch systematically modulates the tap timing. The extent of the modulation
      depended on the relative intensity of the T and D tones, but not on their pitch
      distance. Experiment 2 then used a synchronization-continuation paradigm in which
      D sequences of different tempi were introduced only during continuation tapping.
      Although the D sequences rarely captured the taps completely, they did increase
      the tapping variability and deviations from the correct tempo. Furthermore, they
      eliminated the negative correlation between successive inter-tap intervals and
      led to intermittent phase locking when the tapping period was close to the period
      of the D sequence. These distractor effects occurred regardless of whether or not
      the taps generated auditory feedback tones. The distractor effects thus depend
      neither on the intention to synchronize with a T sequence nor on the simultaneous
      perception of two auditory sequences. Rather, they seem to reflect a basic
      attraction of rhythmic movement to auditory rhythms.

PMID- 16098945
TI  - The perceived importance of sensory modalities in product usage: a study of self
      reports.
AB  - Although popular belief holds that vision dominates human experience, this does
      not necessarily imply that people regard vision as the most important sensory
      modality during the interaction with every product. Instead, the relative
      importance of the different modalities is likely to depend on the type of product
      and on the task performed. In Study 1, respondents reported how important they
      found vision, audition, touch, taste, and smell during the use of 45 different
      products. In Study 2, the respondents answered a similar question for the
      evaluation of the safety, ease of use, and enjoyment experienced for 15 products.
      Importance ratings for the sensory modalities differed considerably between the
      products. Differences due to the types of evaluations were smaller. Averaged over
      products and evaluation types, vision was the most important sensory modality for
      product evaluations, followed by touch, smell, audition, and taste. However, for
      about half of the individual products, the importance ratings for vision were
      lower than for one of the other modalities. These findings are in line with the
      view that vision is regarded the dominant modality, because it plays an important
      part in many and an irrelevant part in virtually no product experiences.

PMID- 16098946
TI  - Artemisinin-based combination therapies (ACTs): best hope for malaria treatment
      but inaccessible to the needy!
AB  - Artemisinin-based combination therapies (ACTs) are the best anti-malarial drugs
      available now. Artemisinin enhances efficacy and has the potential of lowering
      the rate at which resistance emerges and spreads. Under low transmission
      intensity, ACTs have an additional public health benefit of reducing the overall
      malaria transmission and studies are urgently needed to investigate modalities of
      attaining similar benefits under high transmission. Despite being recommended by
      WHO since 2001, overall deployment of ACT has been slow. Limiting factors are
      high cost, limited knowledge and public awareness on the concept of combination
      therapy (CT) and ACT in particular, limited knowledge on safety of ACTs in
      pregnancy, operational issue such as inappropriate drug use, lack of suitable
      drug formulations, lack of post-marketing surveillance (PMS) systems, and the
      imbalance between demand and supply. Through concerted efforts of multilateral
      organizations, the local scientific community with involvement of policy-makers
      progress has been on several fonts leading to improved ACT uptake rates in the
      last 2 years. Of 43 countries that had adopted ACT by February 2005, 18 (42%)
      adopted the policy in 2004. Preference to co-formulated Coartem has led to a
      surge in its demand with consequent shortage. Alternative ways for increased
      production of ACTs are urgently needed otherwise most policies will remain
      adopted on paper. Despite limitations, opportunities are opening up for effective
      malaria control. Insecticides, insecticide-treated nets (ITNs) and ACTs are
      proven efficacious controls available that should be accessed by many.
      Substantial funding is now available for biomedical malaria research and for
      policy implementation. While the Global Fund is the financial engine behind the
      scaling up of ACT uptake, delays in cash flow after grant approval has led to
      many countries adopting ACT in 2004 but only few (nine) implementing it. Clear
      policies on granted funds and minimal politics within funding agencies might
      improve the situation. Increased interest in drug development together with the
      public and private sector partnership have led to new anti-malarials, some less
      expensive and therefore affordable by poor malaria endemic countries.
      Dihydroartemisinin-piperaquine (Artekin) has a cost advantage over other ACTs
      (USD 1 for an adult treatment) making it a potential best candidate for
      deployment in Africa. Part of available funds should be invested into capacity
      building and strengthening (personnel, resources and infrastructure) of
      institutions in malaria endemic countries. This will create enabling environment
      and a critical mass of scientists and public health experts to spearhead ACT
      policy implementation. Active involvement of scientists from malaria endemic
      countries in recent International Scientific Forums like the Malaria in Pregnancy
      Working Group and the Consortium on ACT Implementation is the best way forward to
      emulate.

PMID- 16098947
TI  - Oxygen tensioactivity on liquid-metal drops.
AB  - The influence of oxygen on the surface tension of liquid metals is a topic of
      undoubted interest as the formation of oxide films, or even oxygen contamination
      of the metal interface, represents the main source of error in determining the
      surface tension. The evaluation of gas-atmosphere mass exchanges under stationary
      conditions allows the evaluation of an effective oxygen pressure at which the
      oxidation of metal becomes evident. This effective oxygen pressure can be
      considered as a property of the system and, according to experimental evidence,
      can be many orders of magnitude greater than the equilibrium pressure. The
      measurement of the surface tension is a good way of studying interface
      properties, their temporal change and their connections to transport and reaction
      rates. This paper represents a review of a work undertaken with the aim of
      understanding oxygen mass transport at the liquid metal surface in relation to
      the study of capillary phenomena at high temperature.

PMID- 16098948
TI  - A postcolumn alkalinization procedure enhances the sensitivity of fluorescence
      detection of fluorescein-labeled substances in RP-HPLC.

PMID- 16098949
TI  - RNA integrity and in situ RT-PCR in dento-alveolar tissues after microwave
      accelerated demineralisation.
AB  - OBJECTIVE: The structural organization of oral soft tissue and its relationship
      with highly calcified teeth are difficult to preserve unless tissues are
      decalcified, paraffin embedded and subsequently sectioned. However, enamel
      decalcification time and its negative impact on RNA integrity makes it difficult
      to effectively analyse in situ gene expression. This study examined the impact of
      microwave-enhanced decalcification on processing time, RNA integrity and
      detection of in situ mRNA expression in hard and soft tissue for cell type
      specific markers of Keratinocyte growth factor receptor, Scleraxis and
      Osteonectin. DESIGN: Maxillas and mandibles were obtained from three male Wistar
      strain rats. Right side tissues were decalcified using a microwave plus 10% EDTA
      solution (M+) while left side tissues were decalcified in 10% EDTA solution alone
      (M-). RESULTS: Microwave use reduced decalcification time by up to 50% and had no
      significant impact on morphology, RNA quality and in situ detection of gene
      expression relative to the M-group. CONCLUSIONS: In situ RT-PCR gene expression
      of microwave decalcified paraffin-embedded oral tissues is an effective technique
      to localize in situ gene expression while maintaining excellent soft and hard
      tissue architecture.

PMID- 16098950
TI  - N-acetyl-L-cysteine suppresses TGF-beta signaling at distinct molecular steps:
      the biochemical and biological efficacy of a multifunctional, antifibrotic drug.
AB  - The interrelated signaling via TGF-beta1 and reactive oxygen species has a
      profound impact on fibrogenesis and is therefore selected as target for
      antifibrotic therapies. This prompted us to investigate the influence of the
      antioxidant N-acetyl-L-cysteine on TGF-beta signaling in culture-activated
      hepatic stellate cells, the most relevant pro-fibrogenic cell type in liver.
      Dissection of the molecular steps involved in TGF-beta signaling revealed that N
      acetyl-L-cysteine dose-dependently abrogated the induction of the TGF-beta1
      signaling reporter gene activation, the phosphorylation of Smad2 and Smad3, and
      the up-regulation of Smad7 mRNA. By means of Western blot analysis and cross
      linking experiments, it was demonstrated that these effects are based on
      disintegration of TGF-beta1 and the TGF-beta receptor endoglin, as well as a
      reduced ligand binding capacity of betaglycan. We conclude that N-acetyl-L
      cysteine is a specific inhibitor of TGF-beta signaling targeting different
      components of the TGF-beta signaling machinery. In conclusion, these findings
      suggest that this non-toxic aminothiol downregulates TGF-beta signal transduction
      thereby mediating beneficial effects on experimental liver fibrosis characterized
      by TGF-beta hyperactivity.

PMID- 16098951
TI  - Neurogenesis in the adult rat brain after intermittent hypoxia.
AB  - Intermittent hypoxia has been found to prevent brain injury and to have a
      protective role in the CNS. To address the possible causes of this phenomenon, we
      made investigative effort to find out whether intermittent hypoxia affects
      neurogenesis in the adult rat brain by examining the newly divided cells in the
      subventricular zone (SVZ) and dentate gyrus (DG). The adult rats were treated
      with 3000 and 5000 m high altitude 4 h per day for 2 weeks consecutively. 5-Bromo
      2-deoxyuridine-5-monophosphate (BrdU) immunocytochemistry demonstrated that the
      BrdU-labeled cells in the SVZ and DG increased after 3000 and 5000 m intermittent
      hypoxia. The number of BrdU-labeled cells in the SVZ returned to normal level 4
      weeks following intermittent hypoxia. However, the BrdU-labeled cells in the DG
      had a twofold increase 4 weeks subsequent to intermittent hypoxia. From these
      data, we conclude that intermittent hypoxia facilitates the proliferation of
      neural stem cells in situ, and that the newly divided cells in the SVZ and DG
      react differently to hypoxia. We are convinced by these findings that the
      proliferation of neural stem cells in SVZ and DG may contribute to adaptive
      changes following intermittent hypoxia.

PMID- 16098952
TI  - Unilateral cortical application of tumor necrosis factor alpha induces asymmetry
      in Fos- and interleukin-1beta-immunoreactive cells within the corticothalamic
      projection.
AB  - A unilateral microinjection of tumor necrosis factor alpha (TNFalpha) (150 ng)
      onto the primary somatosensory cortex induces state-dependent asymmetries in
      electroencephalographic (EEG) slow wave activity during non-rapid eye movement
      sleep in rats [H. Yoshida, Z. Peterfi, F. Garcia-Garcia, R. Kirkpatrick, T.
      Yasuda, J.M. Krueger, State-specific asymmetries in EEG slow wave activity
      induced by local application of TNF alpha, Brain Res. 1009 (2004) 129-136]. In
      the current study, analogous TNFalpha injections were performed to determine Fos-
      and interleukin-1beta (IL1beta) immunoreactivity (IR). A unilateral
      microinjection of TNFalpha increased the number of Fos- and IL1beta-IR cells in
      the primary somatosensory cortex relative to the contralateral side that received
      heat-inactivated TNFalpha. These asymmetric TNFalpha-induced increases in the
      number of Fos- and IL1beta-IR cells were evident along the outside surface of the
      cortex (mainly layers II and III) in a restricted rostral to caudal zone.
      Asymmetrical increases in the number of Fos-IR cells were also observed in the
      subcortical region that receives the main cortical projection from the
      somatosensory cortex, the somatic region of the reticular nucleus of the thalamus
      (reticular thalamus). The IL1beta-IR cells double-labeled with glial fibrillary
      acidic protein (GFAP), suggesting that many of the IL1beta-IR cells were
      astrocytes. The number of the IL1beta-IR cells in the reticular thalamus
      increased significantly ipsilateral to the TNFalpha injection. Current results
      indicated that Fos- and IL1beta-IR may be utilized to study the functional
      neuroanatomy involved in the TNFalpha-mediated state-dependent enhancement of EEG
      slow wave activity.

PMID- 16098953
TI  - Neuropeptide Y induces torpor-like hypothermia in Siberian hamsters.
AB  - Intracerebroventricular (ICV) injections of neuropeptide Y (NPY) are known to
      decrease body temperature (Tb) of laboratory rats by 1-3 degrees C. Several NPY
      pathways in the brain terminate in hypothalamic structures involved in energy
      balance and thermoregulation. Laboratory rats are homeothermic, maintaining Tb
      within a narrow range. We examined the effect of ICV injected NPY on Tb in the
      heterothermic Siberian hamster (Phodopus sungorus), a species that naturally
      undergoes daily torpor in which Tb decreases by as much as 15-20 degrees C.
      Minimum effective dose was determined in preliminary testing then various doses
      of NPY were tested in cold-acclimated Siberian hamsters while food was withheld.
      NPY markedly reduced Tb in the heterothermic Siberian hamster. In addition, the
      reduction in Tb in 63% of the observations was sufficient to reach the criterion
      for daily torpor (Tb < 32 degrees C for at least 30 min). Neither the incidence
      of torpor nor its depth or duration was related to NPY dose. Both likelihood and
      magnitude of response varied within animals on different test days. NPY decreased
      24-h food intake and this was exaggerated in the animals reaching criterion for
      torpor; the decrease in food intake was positively correlated with the magnitude
      of the decrease in Tb. The mild hypothermia seen in homeothermic laboratory rats
      after NPY injected ICV is exaggerated, often greatly, in the heterothermic
      Siberian hamster. NPY treatment may be activating hypothalamic systems that
      normally integrate endogenous torpor-producing signals and initiate torpor.

PMID- 16098954
TI  - Chronic daily intrathecal injections of a large volume of fluid increase mast
      cells in the thalamus of mice.
AB  - Mast cells are found in the central nervous system (CNS) as well as in the
      periphery. In the brain of mice, they are localized primarily in the thalamus and
      meninges. Although their numbers increase in response to stress, the mediator of
      their recruitment is not known. During studies in which drugs were delivered
      intrathecally in a volume sufficiently large to distribute to the brain, we
      discovered that repeated daily injections of this large volume increased the
      number of mast cells in the thalamus. The increase was not due to changes in
      electrolyte composition of the cerebrospinal fluid (CSF) as chronically
      administered artificial CSF produced similar effects. Repeated injections of even
      small volumes (2 mul) increased mast cells in the medial intralaminar (Med),
      ventral posterior (VP) and posterior (Po) nuclei. Increasing the volume injected
      daily to 20 mul increased mast cells in the lateral intralaminar (Lat),
      laterodorsal (LD), ventrolateral (VL) and lateral geniculate (LG) nuclei and
      further increased those in the lateral extension of the Po nucleus. Thus, small
      and large volumes augment distinct populations of mast cells. While stem cell
      factor (SCF) is abundant in the CNS and is chemotactic to mast cells in the
      periphery, thalamic mast cells in the rodent do not express c-kit, the SCF
      receptor, suggesting that this factor may not be responsible for the effect.
      Consistent with this, centrally injected SCF was incapable of increasing thalamic
      mast cell populations after either single or chronic (21 days) daily injections
      compared to the effect of saline alone. Although the mechanism is not known,
      repeated injections of a large volume of fluid dramatically increase mast cells
      in the CNS, a phenomenon that may be relevant to clinical conditions of increased
      CSF pressure or volume.

PMID- 16098955
TI  - Evidence for a role of energy dysregulation in the MDMA-induced depletion of
      brain 5-HT.
AB  - Although the exact mechanism involved in the long-term depletion of brain
      serotonin (5-HT) produced by substituted amphetamines is not completely known,
      evidence suggests that oxidative and/or bioenergetic stress may contribute to 3,4
      methylenedioxymethamphetamine (MDMA)-induced 5-HT toxicity. In the present study,
      the effect of supplementing energy substrates was examined on the long-term
      depletion of striatal 5-HT and dopamine produced by the local perfusion of MDMA
      (100 microM) and malonate (100 mM) and the depletion of striatal and hippocampal
      5-HT concentrations produced by the systemic administration of MDMA (10 mg/kg
      i.p. x4). The effect of systemic administration of MDMA on ATP levels in the
      striatum and hippocampus also was examined. Reverse dialysis of MDMA and malonate
      directly into the striatum resulted in a 55-70% reduction in striatal
      concentrations of 5-HT and dopamine, and these reductions were significantly
      attenuated when MDMA and malonate were co-perfused with nicotinamide (1 mM).
      Perfusion of nicotinamide or ubiquinone (100 microM) also attenuated the
      depletion of 5-HT in the striatum and hippocampus produced by the systemic
      administration of MDMA. Finally, the systemic administration of MDMA produced a
      30% decrease in the concentration of ATP in the striatum and hippocampus. These
      results support the conclusion that MDMA produces a dysregulation of energy
      metabolism which contributes to the mechanism of MDMA-induced 5-HT neurotoxicity.

PMID- 16098956
TI  - Synthesis of some derivatives of C-(1-deoxy-1-N-substituted-D
      glucopyranosyl)formic acid (D-gluco-hept-2-ulopyranosonic acid) as potential
      inhibitors of glycogen phosphorylase.
AB  - Per-O-benzoylated derivatives (amide, methyl ester and glycinamide) of C-(1-azido
      1-deoxy-alpha-D-glucopyranosyl)formic acid obtained by azide substitution in the
      corresponding C-(1-bromo-1-deoxy-beta-D-glucopyranosyl)formic acid derivatives
      were debenzoylated by the Zemplen-protocol. Per-O-benzoylated C-(1-azido-1-deoxy
      alpha-D-glucopyranosyl)formamide was dehydrated by oxalyl chloride-DMF to give
      the corresponding nitrile, while from its reduction mixture obtained by Raney
      nickel or sodium hydrogentelluride C-(1-amino-1-deoxy-beta-D
      glucopyranosyl)formamide could be isolated. Acetylation of this amino-amide by
      Ac2O/Py and subsequent debenzoylation gave C-(1-acetamido-1-deoxy-beta-D
      glucopyranosyl)formamide. Applying the same conditions to the crude reduction
      mixture allowed the alpha-anomer to be isolated as a minor component. An
      alternative pathway to produce the above beta-anomer appeared in the reaction of
      C-(1-bromo-1-deoxy-beta-D-glucopyranosyl)formamide with CH3CN in the presence of
      Ag2CO3 to yield 1-acetamido-2,3,4,6,-tetra-O-benzoyl-1-deoxy-beta-D
      glucopyranosyl cyanide, which was hydrated, in the presence of TiCl4, to the
      formamide. Some of the new compounds were shown to be weak inhibitors of muscle
      glycogen phosphorylase b.

PMID- 16098957
TI  - Statins prevent pulsatile stretch-induced proliferation of human saphenous vein
      smooth muscle cells via inhibition of Rho/Rho-kinase pathway.
AB  - OBJECTIVE: Pulsatile forces regulate vascular remodeling and trigger vascular
      diseases such as saphenous vein graft disease. The saphenous vein is exposed to
      high pressure and pulsatility only after implantation. Statins have been proved
      to reduce the incidence of vein graft failure. Thus, we investigated the
      molecular mechanisms of pulsatile stretch-induced saphenous vein smooth muscle
      cell (SMC) proliferation and potential beneficial effects of statins. METHODS AND
      RESULTS: Human saphenous vein SMCs were subjected to cyclic stretch (60
      cycles/min) in Flex I plates. Cerivastatin and simvastatin significantly
      prevented stretch-induced increase in SMC proliferation. Stretch induced the
      membrane accumulation of Rho A and Rho kinase inhibitors (Y-27632 and
      hydroxyfasudil) and dominant negative Rho A mutant significantly prevented
      stretch-induced SMC proliferation. In addition, stretch increased the levels of
      both p44/42 mitogen-activated protein (MAP) kinase and Akt phosphorylation. MAP
      kinase kinase (MEK)1/2 inhibitor U0126, phosphatidylinositol (PI) 3-kinase
      inhibitors (wortmannin and LY294002), and dominant negative Akt mutant
      significantly prevented stretch-induced SMC proliferation. Cerivastatin
      significantly prevented stretch-induced membrane accumulation of Rho A. On the
      other hand, stretch-induced phosphorylation of p44/42 MAP kinase and Akt was not
      prevented by cerivastatin. Mevalonate restored the preventive effect of
      cerivasatain on stretch-induced Rho A membrane accumulation. Stretch induced
      hyperphosphorylation of retinoblastoma protein (pRb), which was prevented by
      cerivastatin and the Rho kinase inhibitors. CONCLUSION: Statins prevent stretch
      induced saphenous vein SMC proliferation via inhibition of the Rho/Rho-kinase
      pathway. This may explain the beneficial effects of this class of drug,
      especially for patients after coronary artery bypass grafting.

PMID- 16098958
TI  - Protective effect of green tea on erythrocyte membrane of different age rats
      intoxicated with ethanol.
AB  - It is known that aging is characterized by changes in cell metabolism resulting
      in modification of the structure and function of cell membrane components which
      is mainly the consequence of reactive oxygen species action. These disturbances
      are also enhanced by different xenobiotics, e.g. ethanol. Therefore, the aim of
      this paper is to examine green tea influence on total antioxidant status (TAS)
      and on composition and electric charge of erythrocyte membrane phospholipids in
      ethanol intoxicated rats of various ages. Antioxidant abilities of erythrocytes
      were estimated by measuring TAS. Qualitative and quantitative composition of
      phospholipids in the membrane was determined by HPLC, while the extent of
      erythrocytes lipid peroxidation was estimated by HPLC measurement of
      malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels. Electrophoresis was
      used to determine the surface charge density of the rat erythrocyte membrane. It
      was shown that the process of aging was accompanied by a decrease in TAS and in
      the total amount of phospholipids as well as by enhancement of lipid peroxidation
      and increase in surface charge density of erythrocyte membrane. Ethanol
      administration caused, in term, decrease in TAS and increase in the level of all
      phospholipids and lipid peroxidation products. Ethanol as well significantly
      enhanced changes in surface charge density of erythrocyte membrane. The ingestion
      of green tea partially prevented decrease in erythrocyte antioxidant abilities
      observed during aging and ethanol intoxication. Moreover, long-term drinking of
      green tea protects the structure of the erythrocytes membrane disturbed during
      aging process and/or chronic ethanol intoxication.

PMID- 16098959
TI  - Nucleic acid testing for viral burden and viral genotyping.
AB  - BACKGROUND: Molecular diagnostics plays an important role in the diagnosis and
      clinical management of a wide array of infectious diseases. METHODS: Advances in
      molecular technology and methods of detecting nucleic acid sequences have
      revolutionized the field of virology. These developments are reflected by the
      rapid diagnosis and monitoring of viral agents as well as assessment of clinical
      disease associated with viral infections. In addition to many commercially
      available molecular based assays, many laboratories offer in-house developed
      assays for a variety of viral targets. The introduction of real-time PCR
      technology has made a large impact on virology testing. CONCLUSIONS: The role of
      real-time PCR for the diagnosis of viral infections is enhanced by the accuracy,
      rapidity and ability to quantitate viral target sequences.

PMID- 16098960
TI  - Comparative evaluation of the chemopreventive efficacy of green and black tea
      polyphenols in the hamster buccal pouch carcinogenesis model.
AB  - OBJECTIVES: To evaluate the comparative chemopreventive efficacy of green tea
      polyphenols (Polyphenon-E) and black tea polyphenols (Polyphenon-B) on 7,12
      dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP)
      carcinogenesis. DESIGN AND METHODS: Hamsters were divided into 6 groups. Animals
      in group 1 served as controls. Animals in groups 2 and 3 were administered 0.05%
      Polyphenon-E and B, respectively, in the diet. The right buccal pouches of
      animals in groups 4-6 were painted with 0.5% DMBA three times a week for 14
      weeks. While group 4 received no further treatment, hamsters in groups 5 and 6
      received diet containing 0.05% Polyphenon-E and B, respectively. The status of
      carcinogen-metabolising enzymes, lipid peroxidation and glutathione-dependent
      antioxidants in the buccal pouch and liver, as well as the frequency of bone
      marrow micronuclei were used as biomarkers. RESULTS: Application of DMBA induced
      HBP carcinomas, increased genotoxicity with an imbalance in carcinogen
      metabolising enzymes and the cellular redox status. Inhibition of HBP carcinomas
      by Polyphenon-E and B was associated with a significant decrease in phase I
      enzymes, modulation of lipid peroxidation and enhanced antioxidant and phase II
      enzyme activities. CONCLUSION: The greater efficacy of Polyphenon-B in inhibiting
      HBP carcinogenesis suggests that it may have a major impact in the
      chemoprevention of oral cancer.

PMID- 16098961
TI  - Functional, biochemical, and chromatographic characterization of the complete
      [Ca2+]i oscillation-inducing activity of porcine sperm.
AB  - A cytosolic sperm protein(s), referred to as sperm factor (SF), is delivered into
      eggs by the sperm during mammalian fertilization to induce repetitive increases
      in the intracellular concentration of free Ca2+ ([Ca2+]i) that are referred to as
      [Ca2+]i oscillations. [Ca2+]i oscillations are essential for egg activation and
      early embryonic development. Recent evidence shows that the novel sperm-specific
      phospholipase C (PLC), PLCzeta, may be the long sought after [Ca2+]i oscillation
      inducing SF. Here, we demonstrate the complete extraction of SF from porcine
      sperm and show that regardless of the method of extraction a single
      molecule/complex appears to be responsible for the [Ca2+]i oscillation-inducing
      activity of these extracts. Consistent with this notion, all sperm fractions that
      induced [Ca2+]i oscillations, including FPLC-purified fractions, exhibited high
      in vitro PLC activity at basal Ca2+ levels (0.1-5 microM), a hallmark of PLCzeta.
      Notably, we detected immunoreactive 72-kDa PLCzeta in an inactive fraction, and
      several fractions capable of inducing oscillations were devoid of 72-kDa PLCzeta.
      Nonetheless, in the latter fractions, proteolytic fragments, presumably
      corresponding to cleaved forms of PLCzeta, were detected by immunoblotting.
      Therefore, our findings corroborate the hypothesis that a sperm-specific PLC is
      the main component of the [Ca2+]i oscillation-inducing activity of sperm but
      provide evidence that the presence of 72-kDa PLCzeta does not precisely
      correspond with the Ca2+ releasing activity of porcine sperm fractions.

PMID- 16098962
TI  - The chitin synthase genes chs-1 and chs-2 are essential for C. elegans
      development and responsible for chitin deposition in the eggshell and pharynx,
      respectively.
AB  - It is widely accepted that chitin is present in nematodes. However, its precise
      role in embryogenesis is unclear and it is unknown if chitin is necessary in
      other nematode tissues. Here, we determined the roles of chitin and the two
      predicted chitin synthase genes in Caenorhabditis elegans by chitin localization
      and gene disruption. Using a novel probe, we detected chitin in the eggshell and
      discovered elaborate chitin localization patterns in the pharyngeal lumen walls.
      Chitin deposition in these two sites is likely regulated by the activities of chs
      1 (T25G3.2) and chs-2 (F48A11.1), respectively. Reducing chs-1 gene activity by
      RNAi led to eggs that were fragile and permeable to small molecules, and in the
      most severe case, absence of embryonic cell division. Complete loss of function
      in a chs-1 deletion resulted in embryos that lacked chitin in their eggshells and
      failed to divide. These results showed that eggshell chitin provides both
      mechanical support and chemical impermeability essential to developing embryos.
      Knocking down chs-2 by RNAi caused a defect in the pharynx and led to L1 larval
      arrest, indicating that chitin is involved in the development and function of the
      pharynx.

PMID- 16098964
TI  - Matrix metalloproteinase activity synergizes with alpha2beta1 integrins to
      enhance collagen remodeling.
AB  - Cell-matrix interactions transmit a wealth of information about the extracellular
      environment. In return, a variety of responses from the cell are initiated by
      changes in the matrix. One such response involves the positive regulation of
      matrix metalloproteinases (MMPs) by alpha2beta1 integrin attaching to a specific
      extracellular matrix component, collagen. This study explores the relationship
      between mechanical and biochemical functions of alpha2beta1 integrins as it
      pertains to regulating matrix remodeling. To understand this relationship, the
      individual influences of MMP activity and alpha2beta1 integrin function on
      collagen gel contraction were studied. We have observed little evidence of mutual
      participation in matrix remodeling by the alpha2beta1 integrin and MMP activity
      in cell models where alpha2 is minimally expressed. In cells expressing high
      levels of alpha2, we see an increase in gel contraction that is enhanced by MMP
      activity. Measuring tension as it builds within the gel reveals that alpha2beta1
      integrin presence correlates with force output but is insensitive to MMP
      activity. These data strongly suggest that alpha2beta1 regulates collagen gel
      remodeling through multiple simultaneous mechanisms including force generation
      and modulation of MMP activity.

PMID- 16098963
TI  - rap gene encodes Fizzy-related protein (Fzr) and regulates cell proliferation and
      pattern formation in the developing Drosophila eye-antennal disc.
AB  - The rap (retina aberrant in pattern) gene encodes the Fizzy-related protein
      (Fzr), which as an activator of the ubiquitin ligase complex; APC/C (anaphase
      promoting complex/cyclosome) facilitates the cell cycle stage-specific
      degradation of cyclins. Loss-of-function mutations in rap cause unscheduled
      accumulation of cyclin B in the developing eye imaginal disc, resulting in
      additional mitotic cycles and defective patterning of the developing Drosophila
      eye. Targeted mis-expression of rap/fzr in the eye primordial cells causes
      precocious cell cycle exit, and smaller primordial eye fields, which either
      eliminate or drastically reduce the size of the adult eye. Although mitosis is
      inhibited in the mis-expression animals, cells with abnormally large nuclei form
      tumor-like structures from continued endoreplication, cell growth and retinal
      differentiation. Interestingly, overexpression of Rap/Fzr in the eye primordia
      also increases the size of the antennal primordium resulting in the induction of
      ectopic antennae. These results suggest that Rap/Fzr plays an essential role in
      the timely exit of precursor cells from mitotic cycles and indicate that
      mechanisms that regulate cell cycle exit are critical during pattern formation
      and morphogenesis.

PMID- 16098965
TI  - Differential responses of intrinsic and extrinsic innervation of smooth muscle
      cells in rat colitis.
AB  - Intestinal smooth muscle cells receive neural input from axons that originate
      within the intestine, as well as from axons of extrinsic origin. In the inflamed
      intestine, altered motility may arise from damage to the axon/smooth muscle cell
      relationship, but the extent of change is unknown. Western blotting, histology
      and immunocytochemistry were used in the TNBS model of colitis in the rat to
      evaluate intrinsic and extrinsic axon numbers, which were then correlated with
      circular smooth muscle cell (CSMC) number during the time course from the acute
      onset of colitis to apparent recovery, at Day 35 post TNBS. Total axon profiles
      in the circular smooth muscle layer were reduced by nearly 50% on Day 4 of
      colitis, to 428 +/- 82 axons/section from 757 +/- 125 in control (n = 8-14
      animals). The intrinsic innervation density (axon number per CSMC) dropped
      sharply by Day 2 to less than 30% of control. Although CSMC number nearly tripled
      during colitis, innervation density was restored to control levels by Day 6 due
      to a coordinated three-fold increase in axon number. The subpopulation of
      extrinsic axons expressing tyrosine hydroxylase showed a unique pattern during
      colitis, with no initial decrease in axon number, followed by axonal
      proliferation between Days 6 and 16 post-TNBS. We conclude that loss of intrinsic
      axons is an early event in colitis, and although reversed by axonal
      proliferation, transient denervation may promote CSMC hyperplasia as seen in
      earlier work in vitro. Axonal proliferation of both intrinsic and extrinsic axons
      is identified as a major homeostatic mechanism, with distinct patterns of damage
      and repair suggesting a structural basis for the altered motility seen in the
      inflamed colon.

PMID- 16098966
TI  - Improved detectability of experimental allergic encephalomyelitis in excised
      swine spinal cords by high b-value q-space DWI.
AB  - Experimental allergic encephalomyelitis (EAE) is the primary experimental model
      of multiple sclerosis (MS), which involves both inflammation and demyelination
      and is known to be species-dependent. Spinal cord abnormalities were found in
      more than 80% of postmortem specimens of MS patients. In the present study, T1,
      T2 and high b-value q-space diffusion-weighted magnetic resonance imaging (MRI)
      were used, for the first time, to characterize the EAE model in excised swine
      spinal cords. The MR images were compared with histological staining and clinical
      scoring. Although all spinal cords were excised from swine with severe or very
      severe (clinical score between 3 to 5 on a scale of 5) motor impairments, T1- and
      T2-weighted MRI revealed white matter (WM) abnormalities in only five of the ten
      EAE diseased spinal cords studied, while high b-value q-space diffusion weighted
      MRI (q-space DWI) detected WM abnormalities in all diseased spinal cords studied.
      Interestingly, high b-value q-space DWI was able to detect abnormalities in the
      normal appearing white matter (NAWM) even in spinal cords where no plaques were
      identified by the T1- and T2-weighted MR images. Good anatomical correlation was
      observed between the high b-value q-space MR images and histology. The extent of
      DWI abnormalities paralleled the clinical scoring and correlated with histology.
      In addition, areas classified as NAWM by the T1- and T2-weighted MR images that
      showed abnormalities in the q-space DWI were also found to have abnormal
      histology. This improved detection level of the EAE model by high b-value q-space
      DWI over conventional T1-, and T2-weighted MRI is briefly discussed.

PMID- 16098967
TI  - Plasmodium falciparum: stage specific effects of a selective inhibitor of lactate
      dehydrogenase.
AB  - Plasmodium falciparum lactate dehydrogenase (PfLDH) is essential for ATP
      generation. Based on structural differences within the active site between P.
      falciparum and human LDH, we have identified a series of heterocyclic azole-based
      inhibitors that selectively bind within the PfLDH but not the human LDH (hLDH)
      active site and showed anti-malarial activity in vitro and in vivo. Here we
      expand on an azole, OXD1, from this series and found that the anti-P. falciparum
      activity was retained against a panel of strains independently of their anti
      malarial drug sensitivity profile. Trophozoites had relatively higher PfLDH
      enzyme activity and PfLDH-RNA expression levels than rings and were the most
      susceptible stages to OXD1 exposure. This is probably linked to their increased
      energy requirements and consistent with glycolysis being an essential metabolic
      pathway for parasite survival within the erythrocyte. Further structural
      elaboration of these azoles could lead to the identification of compounds that
      target P. falciparum through such a novel mechanism and with more potent anti
      malarial activity.

PMID- 16098968
TI  - Ubiquitin and ubiquitin-derived peptides as substrates for peptidylglycine alpha
      amidating monooxygenase.
AB  - Ubiquitin (Ub) and the ubiquitin-like proteins (UBLs) mediate an array of
      cellular functions. These proteins contain a C-terminal glycine residue that is
      key to their function. Oxidative conversion of C-terminal glycine-extended
      prohormones to the corresponding alpha-amidated peptide is one step in the
      biosynthesis of bioactive peptide hormones. The enzyme catalyzing this reaction
      is peptidylglycine alpha-amidating monooxygenase (PAM). We report herein that Ub
      is a PAM substrate with a (V/K)(amidation) that is similar to other known peptide
      substrates. This work is significant because PAM and the UBLs co-localize to the
      hypothalamus and the adrenal medulla and are both over-expressed in
      glioblastomas.

PMID- 16098969
TI  - Disruption of perlecan binding and matrix assembly by post-translational or
      genetic disruption of dystroglycan function.
AB  - Dystroglycan is a cell-surface matrix receptor that requires LARGE-dependent
      glycosylation for laminin binding. Although the interaction of dystroglycan with
      laminin has been well characterized, less is known about the role of dystroglycan
      glycosylation in the binding and assembly of perlecan. We report reduced perlecan
      binding activity and mislocalization of perlecan in the LARGE-deficient
      Large(myd) mouse. Cell-surface ligand clustering assays show that laminin
      polymerization promotes perlecan assembly. Solid-phase binding assays provide
      evidence for the first time of a trimolecular complex formation of dystroglycan,
      laminin and perlecan. These data suggest functional disruption of the
      trimolecular complex in glycosylation-deficient muscular dystrophy.

PMID- 16098970
TI  - Increased cellular cholesterol efflux in glycogen storage disease type Ia mice: a
      potential mechanism that protects against premature atherosclerosis.
AB  - Glycogen storage disease type Ia (GSD-Ia) patients manifest a pro-atherogenic
      lipid profile but are not at elevated risk for developing atherosclerosis. Serum
      phospholipid, which correlates positively with the scavenger receptor class B
      type I (SR-BI)-mediated cholesterol efflux, and apolipoprotein A-IV and E,
      acceptors for ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol
      transport, are increased in GSD-Ia mice. Importantly, sera from GSD-Ia mice are
      more efficient than sera from control littermates in promoting SR-BI- and ABCA1
      mediated cholesterol effluxes. As the first step in reverse cholesterol
      transport, essential for cholesterol homeostasis, these observations provide one
      explanation why GSD-Ia patients are apparently protected against premature
      atherosclerosis.

PMID- 16098971
TI  - Excitation energy trapping in photosystem I complexes depleted in Lhca1 and
      Lhca4.
AB  - We report a time-resolved fluorescence spectroscopy characterization of
      photosystem I (PSI) particles prepared from Arabidopsis lines with knock-out
      mutations against the peripheral antenna proteins of Lhca1 or Lhca4. The first
      mutant retains Lhca2 and Lhca3 while the second retains one other light
      harvesting protein of photosystem I (Lhca) protein, probably Lhca5. The results
      indicate that Lhca2/3 and Lhca1/4 each provides about equally effective energy
      transfer routes to the PSI core complex, and that Lhca5 provides a less effective
      energy transfer route. We suggest that the specific location of each Lhca protein
      within the PSI-LHCI supercomplex is more important than the presence of so-called
      red chlorophylls in the Lhca proteins.

PMID- 16098972
TI  - Ectoine and hydroxyectoine inhibit aggregation and neurotoxicity of Alzheimer's
      beta-amyloid.
AB  - beta-Amyloid peptide (Abeta) is the major constituent of senile plaques, the key
      pathological feature of Alzheimer's disease. Abeta is physiologically produced as
      a soluble form, but aggregation of Abeta monomers into oligomers/fibrils causes
      neurotoxic change of the peptide. In nature, many microorganisms accumulate small
      molecule chaperones (SMCs) under stressful conditions to prevent the
      misfolding/denaturation of proteins and to maintain their stability. Hence, it is
      conceivable that SMCs such as ectoine and hydroxyectoine could be potential
      inhibitors against the aggregate formation of Alzheimer's Abeta, which has not
      been studied to date. The current work shows the effectiveness of ectoine and
      hydroxyectoine on the inhibition of Abeta42 aggregation and toxicity to human
      neuroblastoma cells. The characterization tools used for this study include
      thioflavin-T induced fluorescence, atomic force microscopy and cell viability
      assay. Considering that ectoine and hydroxyectoine are not toxic to cellular
      environment even at concentrations as high as 100 mM, the results may suggest a
      basis for the development of ectoines as potential inhibitors associated with
      neurodegenerative diseases.

PMID- 16098973
TI  - The parkinsonism producing neurotoxin MPP+ affects microtubule dynamics by acting
      as a destabilising factor.
AB  - Dysfunction of the microtubule system is emerging as a contributing factor in a
      number of neurodegenerative diseases. Looking for the potential role played by
      the microtubule cytoskeleton in neuron degeneration underlying Parkinson's
      disease (PD), we investigate the influence of the parkinsonism producing
      neurotoxin 1-methyl-4-phenylpyridinium (MPP+) on microtubule dynamics. We find
      that it acts as a strong catastrophe promoter causing a decrease of the average
      length of microtubules assembled from purified tubulin. We also find that it
      reduces the number of microtubules nucleated from purified centrosomes. Finally,
      binding assays demonstrate that the neurotoxin binds specifically to tubulin in
      the microtubule lattice in a close to stoichiometric manner. This paper provides
      the first evidence that dynamic instability of microtubules is specifically
      affected by MPP+ and suggests that it could play a role in neuronal cell death
      underlying PD.

PMID- 16098974
TI  - Changes in linkage pattern of glucan products induced by substitution of Lys
      residues in the dextransucrase.
AB  - Dextransucrase S (DSRS) is the only active glucansucrase that has been found in
      Leuconostoc mesenteroides NRRL B-512F strain. Native DSRS produces mainly 6
      linked glucopyranosyl residue (Glcp), while Escherichia coli recombinant DSRS was
      observed to produce a glucan consisting of 70% 6-linked Glcp and 15% 3,6-Glcp.
      Lys residues were introduced at the N-terminal end of the core domain by site
      directed mutagenesis. In glucans produced by the one-point mutants T350K and
      S455K, the amount of 6-linked Glcp was increased to about 85% of the total glucan
      produced, more similar in structure to native B-512F dextran. The double mutant
      T350K/S455K produced adhesive, water-insoluble glucan with 77% 6-linked Glcp, 8%
      3,6-linked Glcp and 4% 2,6-linked Glcp. The T350K/S455K mutant exhibited a 10
      fold increase in glucosyltransferase activity over those of the parental DSRS
      His(6) and its T350K and S455K mutants. This is the first report demonstrating a
      change in the properties of a dextransucrase or a related glucosyltransferase
      through simple site-directed mutagenesis to create 2,6-linked Glcp.

PMID- 16098975
TI  - Importance of a repetitive nine-residue sequence motif for intracellular
      stability and functional structure of a family I.3 lipase.
AB  - PML5 is a functional derivative of a family I.3 lipase from Pseudomonas sp. MIS38
      and contains five repeats of a nine-residue sequence motif. Two aspartate
      residues within the second and third repetitive sequences of PML5 were replaced
      by Ala. The secretion level, intracellular accumulation level, and stability of
      the resultant mutant protein were greatly reduced as compared to those of PML5.
      In addition, this mutant protein was inactive and did not bind Ca2+ ion. We
      propose that the repetitive sequences of PML5 form a beta-roll structure in the
      cells and thereby contribute to the intracellular stability and secretion
      efficiency of the protein.

PMID- 16098976
TI  - Transthyretin-related proteins function to facilitate the hydrolysis of 5
      hydroxyisourate, the end product of the uricase reaction.
AB  - Purine catabolic pathway in Bacillus subtilis is consisted of more than 14 genes.
      Among these genes, pucL and pucM are required for uricase activity. While PucL is
      known to encode the uricase itself, the function of PucM is still unclear
      although this protein is also indispensable for uric acid decomposition. Here, we
      provide evidence that PucM, a transthyretin-related protein, functions to
      facilitate the hydrolysis of 5-hydroxyisourate, the end product of the uricase
      reaction. Based on these results, we propose that transthyretin-related proteins
      present in diverse organisms are not functionally related to transthyretin but
      actually function as a hydroxyisourate hydrolase.

PMID- 16098977
TI  - Emergency obstetric care in Pakistan: potential for reduced maternal mortality
      through improved basic EmOC facilities, services, and access.
AB  - OBJECTIVE: To ascertain and compare compliance with UN emergency obstetric care
      (EmOC) recommendations by public health care centers in Pakistan's Punjab and
      Northwest Frontier Province (NWFP) provinces. METHOD: Cross-sectional data were
      collected from July through September 2003 using UN process indicators. From each
      province, 30% of districts (n=19); were randomly selected; all public health
      facilities providing EmOC services (n=170) were included. RESULTS: The study
      found that out of 170 facilities only 22 were providing basic and 37
      comprehensive EmOC services in the areas studied. Only 5.7% of births occurred in
      EmOC health facilities. Met need was 9% and 0.5% of women gave birth by cesarean
      section. The case fatality rate was a low 0.7%, probably due to poor record
      keeping. Access and several indicators were better in NWFP than in Punjab.
      CONCLUSION: Almost all indicators were below UN recommendations. Health policy
      makers and planners must take immediate, appropriate measures at district and
      hospital levels to reduce maternal mortality.

PMID- 16098978
TI  - Cyclical alendronate treatment in postmenopausal women with osteoporosis.

PMID- 16098979
TI  - Abortion procedures in a tertiary care institution in India.
AB  - OBJECTIVE: To determine the complications rate of termination of pregnancy (TOP)
      and the risk factors for complications following TOP. METHODS: Retrospective
      observational study of the records of 1287 women who underwent TOP in the
      Department of Obstetrics and Gynaecology of the Postgraduate Institute of Medical
      Education and Research, Chandigarh, India, between 1997 and 2001. First-trimester
      abortion was performed in 1088 women (85%) and second-trimester abortion in 199
      women (15%). Most women (76%) were aged between 26 and 30 years; they were
      educated and requested TOP primarily to limit the number of their children or to
      space their births. A malformed fetus was the indication for TOP in 5.9% cases,
      and 16% of the women had medical disorders associated with the pregnancy. Suction
      evacuation was the method of choice for first-trimester abortion (88%);
      dinoprostone gel and extra-amniotic saline solution plus oxytocin infusion were
      the primary methods (71%) for second-trimester abortion. RESULTS: Uterine
      perforation occurred in 1 patient (0.09%) after a first-trimester abortion. The
      total rate of complications was 3.79% after first-trimester and 4.0% after second
      trimester abortions. Excessive hemorrhage and retained placenta were chief
      complications associated with second-trimester abortion. Incomplete abortion
      (1.5%) and minor infection were seen in 2.3% patients. The rate of complications
      was higher among parous women. Postabortion insertion of a CuT intrauterine
      device increased the need for a second course of antibiotics. CONCLUSION:
      Termination of pregnancy is safe if adequate care is taken while performing the
      procedure.

PMID- 16098980
TI  - Incidence and outcomes of breech presentation at term in newborns with congenital
      postural deformities.

PMID- 16098981
TI  - Cerebral white matter lesions predict both ischemic strokes and myocardial
      infarctions in patients with established atherosclerotic disease.
AB  - BACKGROUND: Cerebral white matter lesions (WML) are regarded as manifestations of
      small vessel disease, but have also been associated with large vessel
      atherosclerosis. We investigated whether WML have a predictive value for future
      ischemic events. METHODS AND RESULTS: Two-hundred-thirty patients with proven
      atherosclerotic disease, recent ischemic stroke (IS, n=70), recent myocardial
      infarction (MI, n=71), or peripheral arterial disease (PAD, n=89) were included.
      The presence of periventricular lesions (PVL) and deep white matter lesions
      (DWML) on MRI at entry and ischemic events during follow-up were registered.
      During follow-up with a mean duration of 3.5+/-1.4 years 22 patients had a MI, 21
      patients suffered an IS and 2 patients died suddenly. The frequency of ischemic
      events during follow-up was higher among patients with PVL than in those without
      PVL (IS: 18% versus 5%, p=0.001; MI: 15% versus 7%, p=0.03; any ischemic event:
      36% versus 11%, p<0.001). DWML was associated only with the combined outcome any
      ischemic event (p=0.04). In multivariate regression analysis the presence of PVL
      was independently associated with IS (HR 3.2 (95%CI 1.3-8.4) and MI (HR 3.4
      (95%CI 1.4-8.0)). CONCLUSION: We observed an association between WML, especially
      PVL, and future ischemic strokes and myocardial infarctions in patients with
      established atherosclerotic disease.

PMID- 16098982
TI  - Determining rigid body transformation parameters from ill-conditioned spatial
      marker co-ordinates.
AB  - The three-dimensional location of a body-fixed axis system is described by
      position and orientation parameters that can be calculated knowing local and
      global coordinates of three or more body-fixed markers. However, marker
      distribution can become ill-conditioned when marker placement is symmetrical with
      respect to the mean of the markers. As symmetry and ill-conditioning increases,
      random errors in marker locations can affect the stability of orientation
      parameters as a result of the mathematical approach adopted. The present study
      investigates the methods of Veldpaus et al. [1988; Journal of Biomechanics 21,
      45], Challis [1995; Biomechanics 28, 733] and Andriacchi et al. [1998; Journal of
      Biomedical Engineering 120, 743] for obtaining segment orientation parameters
      when segment markers ranged from well-defined to highly ill-conditioned depending
      on the symmetry of segment markers. A novel fourth approach is also presented
      that enabled comparisons of the root mean square error of reconstructed marker
      coordinates to verify that an optimal solution was obtained. No single method
      produced optimal results for all axis orientation parameters when reconstructing
      movement trials. The best performed was the method of Veldpaus et al. [1988;
      Journal of Biomechanics 21, 45] based on consistent results and ease of
      implementation. The fourth approach presented provided a reliable method in all
      but the highly ill-conditioned markers, however implementation was
      computationally difficult. The method of Challis [1995; Biomechanics 28, 733] was
      only suited to well-conditioned marker sets which avoided markers lying in a
      single plane with symmetries in marker distribution relative to the mean. The
      method of Andriacchi et al. [1998; Journal of Biomedical Engineering 120, 743]
      produced, at best, orientation parameters that approximated the results obtained
      by least squares methods.

PMID- 16098983
TI  - Measurement of the functional affinity constant of a monoclonal antibody for cell
      surface receptors using kinetic exclusion fluorescence immunoassay.
AB  - Measuring a protein-ligand interaction in solution, away from the ligand's
      cellular environment, may not provide an affinity value applicable in vivo. Here,
      we present a simple, accurate and highly sensitive method for determining the
      antibody affinity to cell surface receptor, hIGFR, and compare this data to
      affinity determined for the soluble receptor. Measurements were performed on both
      full-length bivalent IgG and the monovalent Fab fragments to assess possible
      differences in apparent affinity introduced by avidity of the bivalent IgG.
      Affinities determined for soluble hIGFR were 4 x 10(-12) M for the bivalent IgG
      and monovalent Fab. Comparable affinities of 6 x 10(-12) M and 1 x 10(-11) M for
      the bivalent IgG and Fab, respectively, were also determined for full-length
      hIGFR on cell surface. The method described allows estimation of reactant
      concentrations (anti-IGFR antibody) relative to one known reference concentration
      (the concentration of soluble hIGFR in our case) allowing us to estimate the
      average receptor density on the cell surface. Taken together, we believe these
      data can provide valuable insight into antibody behavior in vivo, especially in
      the case of insoluble or difficult to purify transmembrane receptors.

PMID- 16098984
TI  - Intra-specific variation in strategic ejaculation according to level of polyandry
      in Callosobruchus chinensis.
AB  - Optimal sperm allocation should differ according to the level of polyandry within
      a population, because the risk of sperm competition depends on the re-mating
      frequency of females. We compared the number of sperm ejaculated by males into
      the female reproductive organ between strains with different levels of polyandry
      in the adzuki bean beetle, Callosobruchus chinensis (Coleoptera: Bruchidae) when
      males were reared in different larval densities in a bean. The results showed
      that males derived from a population with a higher level of polyandry increased
      ejaculatory expenditure when they were reared under higher larval densities. We
      discuss the evolutionary correlation of ejaculatory expenditure to the level of
      polyandry.

PMID- 16098985
TI  - Larval nutrition affects lipid storage and growth, but not protein or
      carbohydrate storage in newly eclosed adults of the grasshopper Schistocerca
      americana.
AB  - Nitrogen availability from dietary protein can have profound effects on the
      physiology and evolutionary ecology of insect herbivores. While many studies
      consider the effects of nutrition on consumption and gross body composition of
      protein and other important nutrients, few consider partitioning to storage for
      future use. I used chemically defined artificial diets to quantitatively
      manipulate the amount of dietary carbohydrates and proteins available to growing
      larvae of the grasshopper Schistocerca americana to determine how larval nutrient
      availability affects growth and all three classes of stored nutrients (proteins,
      lipids, and carbohydrates) carried over from larval feeding into adulthood.
      Larvae on poor diets increased consumption, but could not compensate for diet
      quality, eclosing small and containing no significant nutrient stores at
      adulthood. Individuals fed intermediate to high nutrient content diets as larvae
      were significantly larger and contained a significantly greater proportion of
      lipid stores at adult eclosion, but not protein or carbohydrate stores than
      individuals fed low nutrient content diets. This suggests that larvally derived
      lipid stores may be more important to adult fitness than carbohydrate or protein
      stores. This result is contrary to previous studies performed on the role of
      larval nutrition and allocation to protein stores, and this difference is likely
      due to variation in the relative availability of protein in adult diets across
      species.

PMID- 16098986
TI  - Identification and characterization of proteins from Bacillus thuringiensis with
      high toxic activity against the sheep blowfly, Lucilia cuprina.
AB  - Current control of the sheep blowfly (Lucilia cuprina) relies on chemical
      insecticides, however, with the development of resistance and increasing concerns
      about human health and environmental residues, alternative strategies to control
      this economically important pest are required. In this study, we have identified
      several isolates of Bacillus thuringiensis (Bt), collected from various
      Australian soil samples, that produce crystals containing 130 and 28 kDa
      proteins. These isolates were highly toxic to feeding larvae in both in vitro
      bioassays and in vivo on sheep. By N-terminal amino acid sequencing, we
      identified the smaller crystal band (28 kDa) as a cytological (Cyt) protein. Upon
      solubilization and proteolytic processing by trypsin, the 130 kDa crystal protein
      yielded among others, a truncated 55-60 kDa toxin moiety which exhibited
      larvicidal activity against sheep blowfly. The amino-terminal sequence of the
      trypsin-resistant protein band revealed that this Bt endotoxin was encoded by a
      new cry gene. The novel cry protein was present in all the strains that were
      highly toxic in the larval assay. We have also identified from one of the
      isolates, a novel secretory toxin with larvicidal activity.

PMID- 16098987
TI  - Fast collapse but slow formation of secondary structure elements in the refolding
      transition of E. coli adenylate kinase.
AB  - The various models proposed for protein folding transition differ in their order
      of appearance of the basic steps during this process. In this study, steady state
      and time-resolved dynamic non-radiative excitation energy transfer (FRET and
      trFRET) combined with site specific labeling experiments were applied in order to
      characterize the initial transient ensemble of Escherichia coli adenylate kinase
      (AK) molecules upon shifting conditions from those favoring denaturation to
      refolding and from folding to denaturing. Three sets of labeled AK mutants were
      prepared, which were designed to probe the equilibrium and transient
      distributions of intramolecular segmental end-to-end distances. A 176 residue
      section (residues 28-203), which spans most of the 214 residue molecule, and two
      short secondary structure chain segments including an alpha-helix (residues 169
      188) and a predominantly beta-strand region (residues 188-203), were labeled.
      Upon fast change of conditions from denaturing to folding, the end-to-end
      distance of the 176 residue chain section showed an immediate collapse to a mean
      value of 26 A. Under the same conditions, the two short secondary structure
      elements did not respond to this shift within the first ten milliseconds, and
      retained the characteristics of a fully unfolded state. Within the first 10 ms
      after changes of the solvent from folding to denaturing, only minor changes were
      observed at the local environments of residues 203 and 169. The response of these
      same local environments to the shift of conditions from denaturing to folding
      occurred within the dead time of the mixing device. Thus, the response of the
      CORE domain of AK to fast transfer from folding to unfolding conditions is slow
      at all three conformational levels that were probed, and for at least a few
      milliseconds the ensemble of folded molecules is maintained under unfolding
      conditions. A different order of the changes was observed upon initiation of
      refolding. The AK molecules undergo fast collapse to an ensemble of compact
      structures where the local environment of surface probes seems to be native-like
      but the two labeled secondary structure elements remain unfolded.

PMID- 16098988
TI  - Properties of a mixed ESS candidate in continuous strategy sets.
AB  - An evolutionarily stable strategy (ESS) is a strategy that if almost all members
      of the population adopt, then this population cannot be invaded by any mutant
      strategy. An ESS is not necessarily a possible end point of the evolutionary
      process. Moreover, there are cases where the population evolves towards a
      strategy that is not an ESS. This paper studies the properties of a unique mixed
      ESS candidate in a continuous time animal conflict. A member of a group sized
      three finds itself at risk and needs the assistance of another group member to be
      saved. In this conflict, a player's strategy is to choose the probability
      distribution of the interval between the beginning of the game and the moment it
      assists the player which is at risk. We first assume that a player is only
      allowed to choose an exponential distribution, and show that in this case the ESS
      candidate is an attracting ESS; the population will always evolve towards this
      strategy, and once it is adopted by most members of the population it cannot be
      invaded by mutant strategies. Then, we extend the strategy sets and allow a
      player to choose any continuous distribution. We show that although this ESS
      candidate may no longer be an ESS, under fairly general conditions the population
      will tend towards it. This is done by characterizing types of strategies that if
      established in the population, can be invaded by this ESS candidate, and by
      presenting possible paths of transition from other types of common strategies to
      this ESS candidate.

PMID- 16098989
TI  - Turing pattern with proportion preservation.
AB  - Although Turing pattern is one of the most universal mechanisms for pattern
      formation, in its standard model the number of stripes changes with the system
      size, since the wavelength of the pattern is invariant. It fails to preserve the
      proportionality of the pattern, i.e. the ratio of the wavelength to the size,
      that is often required in biological morphogenesis. To get over this problem, we
      show that the Turing pattern can preserve proportionality by introducing a
      catalytic chemical whose concentration depends on the system size. Several
      plausible mechanisms for such size dependence of the concentration are discussed.
      Following this general discussion, two models are studied in which arising Turing
      patterns indeed preserve the proportionality. Relevance of the present mechanism
      to biological morphogenesis is discussed from the viewpoint of its generality,
      robustness, and evolutionary accessibility.

PMID- 16098990
TI  - Deuterium and its role in the machinery of evolution.
AB  - An argument is presented that the spontaneous mutation rate, the core of
      evolution theory, may be dictated by the deuterium/hydrogen (D/H) abundance
      ratio. This argument is supported by quantum mechanical calculations of the zero
      point energy reduction for DNA base pairs upon deuterium substitution for
      hydrogen and recent experiments that show that the rate of catalytic dsDNA
      unwinding is dependent on the stability of the dsDNA.

PMID- 16098991
TI  - Testing and mapping non-stationarity in animal behavioral processes: a case study
      on an individual female bean weevil.
AB  - Statistical analysis based on two characteristics of a small-world network, and
      on Lempel-Ziv's measure of Kolmogorov-Chaitin's algorithmic complexity are first
      proposed to scan through an individual behavioral sequence for possible existence
      of non-stationarity. Due to fixed window width, these tests have drawbacks in
      mapping out regions of non-stationarity. A non-parametric approach based on
      sparse coding schemes is employed to segment the whole behavioral sequence into
      unequal length segments, thus resultant avoiding further efforts for grouping.
      Then attempts are made to entangle the resultant segmentation with other non
      local behavioral patterns onto such sequence to ascertain that the non
      stationarity corresponds to a sequence of different categories of underlying
      driving force. It is of potential importance that this segmentation, represented
      by a hierarchy of code sequences, provides a natural platform for detecting
      intrinsically coherent behavioral patterns based on continuously recorded data.
      Illustrations throughout the developments are made exclusively on data encoded
      from a nearly 4-h video-recording of a female bean weevil's behavior.

PMID- 16098992
TI  - Nature of stress: differential effects on brain acetylcholinesterase activity and
      memory in rats.
AB  - Effect of acute, chronic-predictable and chronic-unpredictable stress on memory
      and acetylcholinesterase (AChE) was investigated in rats. The animals were
      subjected to 3 type of stressors--(1) acute immobilization stress, (2) chronic
      predictable stress i.e., immobilization daily for 5 consecutive days and (3)
      chronic-unpredictable stress that included reversal of light/dark cycle, over
      night fasting, forced-swimming, immobilization and forced exercise in random
      unpredictable manner daily for 5 consecutive days. Learning and memory function
      was studied by single trial Passive avoidance test. AChE activity was assayed
      spectrophotometrically in the detergent (DS) and salt (SS) soluble fractions in
      different brain regions. Learning was obtained in acute and chronic-predictable
      stress groups but not in chronic-unpredictable group. Acute, chronic-predictable
      and chronic-unpredictable stress caused significant decrease in AChE activity in
      the DS fraction of cortex, hippocampus and hypothalamus as compared to control.
      Results indicate that AChE in DS fraction is predominantly affected in stressed
      and stressed-trained group but cognition is affected only by chronic
      unpredictable stress. In acute and chronic-predictable groups the decreased AChE
      activity in the hippocampal DS fraction during learning may be responsible to
      maintain cognitive function by enhancing the cholinergic activity.

PMID- 16098993
TI  - Inhibition of phosphatase activity enhances preconditioning and limits cell death
      in the ischemic/reperfused aged rat heart.
AB  - Brief, nonlethal episodes of ischemia in the mammalian heart provide
      cardioprotection against the detrimental effects of a longer duration ischemia.
      The manifestation of this preconditioning (PC) phenomenon is initiated by the
      enhanced phosphorylation state of signal transduction proteins. We reported
      previously that PC is decreased in the aged rat myocardium. Although the
      mechanism responsible for this loss is not understood, a reduction in the
      phosphorylation of critical proteins associated with PC may be postulated.
      Experiments were conducted to investigate whether PC in the aged heart can be
      restored with the inhibition of endogenous protein phosphatases thereby enhancing
      phosphorylation of signaling proteins. Levels of phosphatase activities were also
      assessed with adult heart aging. Hearts from young adult (3-4 mo.) and aged (21
      22 mo.) Fischer-344 rats were perfused in the presence or absence of okadaic acid
      (OKA; 0.1 microM). Aged adult hearts were either not preconditioned or were
      preconditioned with two PC cycles (5 min ischemia/5 min reperfusion). Myocardial
      cellular death that developed with a subsequent ischemia was determined with
      triphenyltetrazolium. With PC, 55% of the aged heart after ischemia was no longer
      viable. OKA administered before or after ischemia reduced this ischemia-induced
      cellular death by 29%. Without PC, OKA reduced viability 18% only when present
      before and after the ischemic episode. OKA in the ischemic young heart during
      reperfusion reduced the loss of viability 31%. The Protein Phosphatase 2A (PP2A)
      activity was found to be up to 82% greater in ventricular myocardium of aged
      rats. In conclusion, aging-induced changes in protein dephosphorylation may be
      one mechanism reducing the manifestation of preconditioning in the aged heart.

PMID- 16098994
TI  - Immunological studies on peroxynitrite modified human DNA.
AB  - Peroxynitrite (ONOO(-)) is a strong and potent oxidizing and nitrating agent,
      formed by rapid reaction of two highly reactive, nitric oxide and superoxide
      anion. The action of peroxynitrite generated by synergistic action of
      diethylamine NONOate (a nitric oxide donor) and 1,4-hydroquinone (a superoxide
      donor), on human placental DNA was monitored by ultraviolet and fluorescence
      spectroscopy, melting temperature studies, S1 nuclease digestibility and alkaline
      agarose electrophoresis. The peroxynitrite modified human DNA (ONOO(-)-DNA) was
      found to be highly immunogenic in rabbits inducing high titre immunogen specific
      antibodies. However, the induced antibodies exhibited appreciable cross
      reactivity with various polynucleotides and nucleic acids. The data demonstrate
      that the antibodies, though cross-reactive, preferentially bind ONOO(-)-modified
      epitopes on DNA. Visual detection of immune complex formation with native and
      ONOO(-)-DNA reiterated preferential binding with modified human DNA. DNA modified
      by ONOO(-) presents unique epitopes which may be one of the factors for the
      induction of autoantibodies in cancer patients.

PMID- 16098995
TI  - Paraventricular hypothalamic CB(1) cannabinoid receptors are involved in the
      feeding stimulatory effects of Delta(9)-tetrahydrocannabinol.
AB  - BACKGROUND/AIMS: The paraventricular nucleus of the hypothalamus (PVN) is the
      target of converging orexigenic and anorexigenic pathways originating from
      various hypothalamic sites and is, therefore, considered to be the chief site
      mediating hypothalamic regulation of energy homeostasis. Although a large body of
      evidence suggests that central CB(1) cannabinoid receptors mediate food intake,
      it is not clear whether PVN CB(1) receptors are involved in the control of
      feeding behaviour. The present study therefore examined the effects of intra-PVN
      administration of Delta(9)-tetrahydrocannabinol (THC) and the cannabinoid
      receptor antagonist SR 141716 on feeding. METHODS: After being habituated to the
      test environment and injection procedure, sated rats were injected with SR 141716
      (0.03-3.0 microg, Experiment 1) alone or in combination with THC (5.0 microg,
      Experiment 2) into the PVN. Food intake and locomotor activity then were recorded
      for 120 min. RESULTS: Intra-PVN administration of THC produced a significant
      increase in food intake that was attenuated by SR 141716. Administration of SR
      141716 alone did not affect feeding. Locomotor activity was not significantly
      affected by any drug treatments, suggesting that effects on feeding were not due
      to a non-specific reduction in motivated behaviour. These findings suggest an
      important role for PVN cannabinoid signalling in mediating THC-induced feeding
      behaviour. These results also demonstrate that the blockade of PVN CB(1)
      receptors alone is insufficient to reduce baseline feeding behaviour under these
      conditions.

PMID- 16098996
TI  - Effects of opioid antagonists and morphine in a hippocampal hypoxia/hypoglycemia
      model.
AB  - The influence of opioid antagonists and of morphine on rat hippocampal slices in
      a model of reversible hypoxia/hypoglycemia was investigated by assessment of
      evoked field potentials (population spike amplitude). In control slices, a brief
      hypoxia/hypoglycemia led to a loss of field potentials followed by an impaired
      recovery (40-50% of baseline) during reperfusion. In contrast, restoration was
      significantly improved when the opioid receptor antagonists funaltrexamine (mu)
      or naltrindole (delta) were administered prior to and during
      hypoxia/hypoglycemia. In addition, recovery was improved in brain slices derived
      from mu-opioid receptor-deficient mice as compared to wild-type mice, indicating
      a deleterious role of endogenous opioids in hypoxia/hypoglycemia. Exogenous
      opiate exposure with morphine (0.1, 1.0, 10 microM) prior to hypoxia/hypoglycemia
      caused a slight concentration dependent increase of evoked field potentials. When
      morphine exposure was terminated after 1h and immediately followed by
      hypoxia/hypoglycemia, an impaired recovery of population spike amplitude was
      obtained, dependent on morphine concentration during preincubation. These results
      demonstrate that morphine aggravates neurotoxic effects of hypoxia/hypoglycemia.
      Conversely, when onset of hypoxia/hypoglycemia was delayed for 3h after morphine
      termination, a significantly improved recovery was observed. Similarly, in vivo
      administration of morphine 12h prior to slice preparation resulted in a dose
      dependent improved recovery of field potentials after hypoxia/hypoglycemia. These
      results provide evidence that preconditioning with morphine is able to induce
      neuroprotective effects.

PMID- 16098997
TI  - Vision and touch in ageing: crossmodal selective attention and visuotactile
      spatial interactions.
AB  - We investigated whether ageing affects crossmodal selective attention (the
      ability to focus on a relevant sensory modality and ignore an irrelevant
      modality) and the spatial constraints on such selective processing. Three groups
      of 24 participants were tested: Young (19-25 years), Young-Old (65-72 years) and
      Old-Old (76-92 years). The participants had to judge the elevation of
      vibrotactile targets (upper/index finger and lower/thumb), presented randomly to
      either hand while ignoring concurrent visual distractors. In a second task, the
      role of the target and distractor modalities was reversed. Crossmodal selective
      attention was assessed by comparing performance in the presence versus absence of
      distractors. Spatial constraints on selective attention were also investigated by
      comparing the effect of distractors presented on the same versus opposite side as
      the target. When attending to touch, the addition of visual distractors had a
      significantly larger effect on error rates in both of the older groups as
      compared to the Young group. This indicates that ageing has a detrimental effect
      on crossmodal selective attention. In all three age groups, performance was
      impaired when the target and distractor were presented at incongruent as compared
      to congruent elevations in both tasks. This congruency effect was modulated by
      the relative spatial location of the target and distractor in certain conditions
      for the Young and the Young-Old group. That is, participants in the two younger
      age groups found it harder to attend selectively to targets in one modality, when
      distractor stimuli came from the same side rather than from the opposite side.
      However, no significant spatial modulation was found in the Old-Old group. This
      suggests that ageing may also compromise spatial aspects of crossmodal selective
      attention.

PMID- 16098998
TI  - Disgust in pre-clinical Huntington's disease: a longitudinal study.
AB  - Emotion recognition from both face and voice and experience of emotions were
      investigated in a group of non-symptomatic people at risk of carrying the
      Huntington's disease gene who presented for genetic testing. Based on the results
      of the DNA test, a group of people carrying the Huntington's disease gene (HD+),
      and a group of non-carriers (HD-) were formed. Since we were especially
      interested in the time course of possible deficits in emotion recognition, all
      people at risk were reassessed 6 and 12 months after the initial assessment.
      Recognising facial expressions of disgust was significantly impaired on all three
      assessments in the HD+ group, while recognition of vocal emotions and the
      experience of emotions were largely unaffected, confirming that deficits in
      recognition of facial expressions of disgust are an early correlate of carrying
      the gene for Huntington's disease. The inclusion of a healthy control group (n =
      37) further allowed an estimate of the genetic and environmental contribution to
      deficits in facial emotion recognition.

PMID- 16098999
TI  - Handedness, dichotic-listening ear advantage, and gender effects on planum
      temporale asymmetry--a volumetric investigation using structural magnetic
      resonance imaging.
AB  - Previous research has often examined whether the asymmetrical structure of the
      planum temporale (PT) represents an anatomical correlate of lateralized language
      processing functions, gathering diverging empirical evidence by comparing PT
      asymmetry in subjects with differing handedness, gender, or speech
      lateralization. Apart from other methodological problems, direct comparisons
      between studies are hampered by insufficient assessment and consideration of all
      three potential determinants of structural cerebral asymmetry. Based on
      volumetric assessment of structural Magnetic Resonance Imaging (MRI) scans of 104
      healthy subjects, the present study replicated earlier observations of an overall
      leftward PT asymmetry, which was found to prevail irrespective of handedness,
      gender, or dichotic-listening ear advantage. However, the mean magnitude of this
      leftward asymmetry was not determined by either one of these factors in itself,
      but varied depending on their specific combination. A clear correspondence
      between structural and functional asymmetry was only observed among right-handed
      males. In this particular subgroup, more pronounced structural asymmetry was
      associated with an enlarged PT on the left side, while the enhanced leftward
      asymmetry of female sinistrals resulted from smaller adjusted volumes of their
      right PT. The existence of such complex interactions suggests that future
      research in this area can only be expected to overcome past inconsistencies by
      adequately considering handedness, gender, and speech lateralization.

PMID- 16099000
TI  - Effects of postweaning undernutrition on exploratory behavior, memory and sensory
      reactivity in rats: implication of the dopaminergic system.
AB  - The effects of early undernutrition on behavior and brain biochemistry were
      examined in rats. At weaning, rats were provided either an ad lib diet (control
      group) or maintained at 80% of the weight of their control littermates
      (undernourished group). Three weeks into the diet they were tested in an open
      field. After 6 weeks of diet, HPLC analyses were conducted on sample brains from
      each group to assess levels of dopamine and metabolites, respectively
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum.
      At seven weeks of diet, remaining rats were trained in an 8-arm radial maze, and
      a retention test conducted 72 h after attaining the learning criterion. At
      fourteen weeks of diet, sensory reactivity was measured by tail-immersion in a
      water bath maintained at constant temperature 50 +/- 1 degrees C. Undernourished
      rats exhibited hyperactivity and increased exploratory behavior in the open
      field, as well as increased sensory reactivity in the tail flick test. In the
      radial maze, however, undernourished rats did not differ from controls in either
      learning or retention. Haloperidol (i. p. injection) impaired retention by
      control but not undernourished animals. HPLC analyses showed an increase in
      dopamine turnover in the striatum of undernourished rats. Our results suggest
      that, unlike its effects when induced immediately at birth or in adulthood,
      undernutrition at weaning does not appear to influence learning and retention but
      induced an hyperactivity and alterations in striatal DA turnover which was
      associated with a decrease in responsiveness to i. p. haloperidol injection.

PMID- 16099001
TI  - A survey of the specialist public health workforce in the UK in 2003.
AB  - OBJECTIVES: To identify the number and distribution of public health specialists
      in the UK. STUDY DESIGN: Cross-sectional survey. METHODS: Postal survey of UK
      members and fellows of the Faculty of Public Health and primary care trust
      directors of public health in England in October 2003. RESULTS: Of 1993
      individuals surveyed, 1566 (78%) responded, of whom 1331 reported working as
      consultants or specialists in public health in the UK. Of the 1331, 891 (67%)
      were on the General Medical Council Specialist Register, 53 (4%) were on the
      General Dental Council Register, and 92 (7%) were in the process of applying for
      the Voluntary Register; 295 (22%) did not appear to be on any professional
      register or in the process of applying to the Voluntary Register. This equated to
      a total UK rate of 14.1 per million 'service' public health. There was
      substantial variation by region from 9.3 per million population in Wales and the
      South West to 18.0 per million population in the West Midlands and 19.5 per
      million population in London. An increase of 218 (21%) additional consultants and
      specialists in public health across the UK would be required to bring other
      regions up to the level of the highest region. CONCLUSIONS: This survey, although
      limited, being based on a survey of members and fellows of the Faculty of Public
      Health, shows that specialist public health is under capacity, is resourced in a
      highly variable manner, and needs to be built up to meet the challenges we face.
      A comprehensive workforce plan for public health is urgently needed.

PMID- 16099002
TI  - Passive cigarette smoke exposure in primary school children in Liverpool.
AB  - OBJECTIVE: To assess environmental tobacco smoke (ETS) exposure amongst primary
      school children. METHODS: A descriptive, community-based, cross-sectional study
      of self-reported parental smoking patterns and children's salivary cotinine
      concentrations in 245 children aged 5-11 years attending 10 primary schools in
      Liverpool. RESULTS: The mean age was 7.4 years. The percentage of children living
      in smoking households was higher than the average reported for England (61.4% vs
      53.0%). The average daily number of cigarettes smoked was similar for fathers
      (15.8) and mothers (16.4). The mean salivary cotinine concentration (+/-SD) was
      1.6+/-0.4 ng/ml, and was higher in boys than girls (1.9+/-0.4 vs 1.2+/-0.2 ng/ml,
      P=0.006). The mean cotinine concentration was higher amongst children less than 7
      years of age compared with older children (1.9+/-0.9 vs 1.4+/-0.6 ng/ml, P=0.01).
      Children from disadvantaged socio-economic households (Townsend score > + 6) had
      a mean cotinine level of 1.9+/-0.4 ng/ml, and a higher risk of a positive
      cotinine-validated level (>or=1 ng/ml) [crude odds ratio (OR) 3.5, 95% confidence
      interval (CI) 1.6-5.2). Maternal, but not paternal, cigarette smoke exposure was
      significantly associated with the salivary cotinine-validated level in children
      (adjusted OR 2.5, 95%CI 1.8-3.4). CONCLUSIONS: Maternal smoking, age less than 7
      years, child's gender (male) and low socio-economic status were significant risk
      factors associated with ETS exposure in young school children in Liverpool. The
      level of childhood ETS exposure in this area demonstrates a major public health
      concern that creates a challenge for innovative interactive strategies.

PMID- 16099003
TI  - High risk of hookworm infection among wastewater farmers in Pakistan.
AB  - The health risks of wastewater use in agriculture were investigated in the city
      of Faisalabad, Pakistan, by means of a cross-sectional study. The study showed an
      increased risk of intestinal nematode infection and hookworm infection, in
      particular, in wastewater farmers (OR = 31.4, 95% CI 4.1-243) and their children
      (OR = 5.7, 95% CI 2.1-16) when compared with farming households using regular
      (non-wastewater) irrigation water. Textile labourers living in the same village
      as the wastewater farmers showed a lower risk of hookworm infection than
      wastewater farmers but an increased risk compared with farming households using
      regular irrigation water. Many urban and peri-urban farmers make a living by
      using untreated wastewater in the production of fresh produce for the urban
      market. Banning the use of untreated wastewater would deprive these farmers of
      their livelihood and affect food supply for the urban population. If treatment of
      wastewater is not a feasible option, the promotion of footwear and improved
      hygiene, the construction of toilets, in combination with regular anthelminthic
      treatment, would be suitable alternatives to safeguard the health of wastewater
      farmers and their children.

PMID- 16099004
TI  - Recrudescence of imported falciparum malaria after quinine therapy: potential
      drug interaction with phenytoin.
AB  - Quinine remains a reliable treatment for falciparum malaria in most parts of the
      world. We report recrudescence of imported Plasmodium falciparum malaria
      following quinine treatment in the context of concurrent phenytoin use. Supported
      by a subtherapeutic quinine level, we hypothesise that a drug interaction with
      phenytoin may compromise the efficacy of quinine in the treatment of malaria.

PMID- 16099005
TI  - Uncommon clinical presentations of cutaneous leishmaniasis in Sudan.
AB  - Cutaneous leishmaniasis in Sudan is caused by Leishmania major zymodeme LON1.
      Self-healing usually occurs within 1 year but occasionally its duration is
      prolonged and treatment is required. The clinical forms are ulcers, nodules and
      noduloulcerative lesions. Here we describe seven patients with uncommon lesions
      that were difficult to recognize as Leishmania infections. These included
      mycetoma-like lesions, lesions that resembled L. tropica infection and others.
      One HIV/AIDS patient had Kaposi's sarcoma with Leishmania parasites in the Kaposi
      lesions. Most of these uncommon clinical forms were difficult to treat. The
      diagnosis depended on a high degree of suspicion and the demonstration of
      parasites in smears or culture. PCR was used to characterize parasites from the
      patients described here. Leishmania major was found by kDNA PCR in all patients,
      except one, who had a leishmanioma due to L. donovani. In three patients,
      including one with a L. tropica like-lesion, the parasites were confirmed as L.
      major by gp63 PCR-RFLP.

PMID- 16099006
TI  - Fasciola hepatica in the human eye.
AB  - During intraocular surgery of a 44-year-old woman from Guilan Province in north
      Iran, a small flat parasite was removed from the anterior chamber angle of the
      left eye. According to morphological characterisation of the parasite, it was
      identified as Fasciola hepatica. The route of entry of the parasite was not
      identified. Meanwhile, stool and serology examinations of the patient for
      diagnosis of Fasciola infection were negative. In endemic areas of F. hepatica
      infection, ocular involvement should be considered in cases of uveitis, despite
      no other systemic involvement.

PMID- 16099007
TI  - Control of Biomphalaria pfeifferi population and schistosomiasis transmission in
      Ethiopia using the soap berry endod (Phytolacca dodecandra), with special
      emphasis on application methods.
AB  - The endod (Phytolacca dodecandra)-based schistosomiasis mansoni control project
      was implemented in Ethiopia between 1994 and 1999. The aim was to develop an
      effective, cheap and sustainable method of controlling schistosomiasis. First,
      different formulations of the Ethiopian endod strain 44 (E-44) were compared for
      potency in the laboratory. Secondly, spray and drip-feeding methods were compared
      for simplicity and effectiveness in the field. Lastly, the efficacy of endod
      powder soap was compared with the endod spray method. In Bati stream, endod
      powder soap was distributed to the residents every weekend at laundry sites. In
      Worke stream, endod was sprayed along a 1-km stretch of the stream at 3-month
      intervals. No endod was applied in Harbu stream. The immediate and long-term
      effects of endod application on the snail population and schistosomal infection
      were determined. Using the spray method, 100% snail mortality could be obtained,
      and it was simpler and more effective than the drip-feeding method. Snail
      mortality ranged from 20 to 100% using endod soap. There was a progressive
      decline in the snail population and infection in Bati stream compared with Worke
      stream, mainly due to sustained use of endod soap. The advantages and
      disadvantages of the different endod delivery systems are discussed.

PMID- 16099008
TI  - Detection of muscle calcifications by thigh CT scan in neurocysticercosis
      patients.
AB  - Twenty-five patients with calcified neurocysticercosis (two to four
      intraparenchymal brain calcifications) were asked to have a non-contrasted
      computed tomography (CT) scan of the thighs to determine the frequency of muscle
      calcifications detected by this technique. Thirteen (52%) showed one or more
      muscle calcifications. The numbers of calcifications in the thighs and the brain
      were not correlated. Patients with a positive CT scan for muscle calcifications
      were also examined by X-rays to compare both methods. Only 6 of 13 had visible
      calcifications on X-ray. Thigh CT scans can demonstrate muscle calcifications in
      a significant proportion of patients with calcified neurocysticercosis.

PMID- 16099009
TI  - Spatiotemporal distribution of insecticide resistance in Anopheles culicifacies
      and Anopheles subpictus in Sri Lanka.
AB  - The malaria situation in Sri Lanka worsened during the 1990s with the emergence
      and spread of resistance to the drugs and insecticides used for control.
      Chloroquine resistance has increased rapidly over this period, but adverse
      changes in malaria transmission are more closely associated with insecticide use
      rather than drug resistance. Insecticide susceptibility tests were routinely
      carried out in key anopheline vectors across the country for more than a decade.
      These sentinel data were combined with data collected by other research
      programmes and used to map the spatial and temporal trends of insecticide
      resistance in the main vectors, Anopheles culicifacies and A. subpictus, and to
      examine the relationship between insecticide resistance, changes in national
      spraying regimens and malaria prevalence. Both species had widespread resistance
      to malathion, the insecticide of choice in the early 1990s. Both species were
      initially susceptible to the organophosphate and pyrethroid insecticides used
      operationally from 1993, but some resistance has now been selected. The levels of
      malathion and fenitrothion resistance in A. subpictus were higher in some
      ecological regions than others, which may be related to the distribution of
      sibling species, agricultural pesticide exposure and/or environmental factors.
      The study highlights that the emergence and spread of insecticide resistance is a
      constant threat and that active surveillance systems are vital in identifying key
      vectors and evidence of resistance.

PMID- 16099010
TI  - Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains
      involved in cell-surface expression and cell-to-cell fusion.
AB  - The SARS-coronavirus (SARS-CoV) is the etiological agent of severe acute
      respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates
      membrane fusion events during virus entry and virus-induced cell-to-cell fusion.
      To delineate functional domains of the SARS-CoV S glycoprotein, single point
      mutations, cluster-to-lysine and cluster-to-alanine mutations, as well as
      carboxyl-terminal truncations were investigated in transient expression
      experiments. Mutagenesis of either the coiled-coil domain of the S glycoprotein
      amino terminal heptad repeat, the predicted fusion peptide, or an adjacent but
      distinct region, severely compromised S-mediated cell-to-cell fusion, while
      intracellular transport and cell-surface expression were not adversely affected.
      Surprisingly, a carboxyl-terminal truncation of 17 amino acids substantially
      increased S glycoprotein-mediated cell-to-cell fusion suggesting that the
      terminal 17 amino acids regulated the S fusogenic properties. In contrast,
      truncation of 26 or 39 amino acids eliminating either one or both of the two
      endodomain cysteine-rich motifs, respectively, inhibited cell fusion in
      comparison to the wild-type S. The 17 and 26 amino-acid deletions did not
      adversely affect S cell-surface expression, while the 39 amino-acid truncation
      inhibited S cell-surface expression suggesting that the membrane proximal
      cysteine-rich motif plays an essential role in S cell-surface expression.
      Mutagenesis of the acidic amino-acid cluster in the carboxyl terminus of the S
      glycoprotein as well as modification of a predicted phosphorylation site within
      the acidic cluster revealed that this amino-acid motif may play a functional role
      in the retention of S at cell surfaces. This genetic analysis reveals that the
      SARS-CoV S glycoprotein contains extracellular domains that regulate cell fusion
      as well as distinct endodomains that function in intracellular transport, cell
      surface expression, and cell fusion.

PMID- 16099011
TI  - Studies on the potential use of CD38 expression as a marker for the efficacy of
      anti-retroviral therapy in HIV-1-infected patients in Thailand.
AB  - The monitoring of the efficacy of anti-retroviral therapy (ART) is becoming an
      important issue in the developing world. The current use of CD4 counts, plasma
      viral loads, and monitoring of drug-resistant viruses are at present either
      uninformative or costly. Thus, more new cost-effective and practical techniques
      need to be established and implemented. Towards this goal, our lab has carried
      out studies on the potential use of CD38 frequency and density expression by flow
      analysis as a means to assess the efficacy of ART. Results of our studies using
      whole blood sample from normal healthy donors indicate that CD38 is expressed by
      a high frequency of not only CD4+ and CD8+ T cells but also most hematopoietic
      cell lineages analyzed. Detailed studies of CD38 expression along with other cell
      surface markers using whole blood sample from HIV-1-infected patients showed that
      the most discriminating change was the increased frequency and density of CD38
      expression by CD3+CD8+ T cells. Of importance was our preliminary finding that a
      reversal of the increased frequency and density of CD38 expression by CD8+ T
      cells only appeared in the whole blood sample from patients who were responders
      to ART but not those who were drug failures. These initial data provide a
      platform and incentive for larger cohort studies including prospective pre- and
      post-ART for the institution of such monitoring techniques in resource limited
      settings.

PMID- 16099012
TI  - Inactivation of murine leukaemia virus by exposure to visible light.
AB  - Prolonged storage of murine leukaemia virus in ambient light leads to a loss of
      infectivity. Particle integrity and envelope incorporation are unaffected;
      rather, the defect is functional and intrinsic to the viral core. Light in the
      violet part of the visible spectrum (wavelength 420-430 nm) is responsible for
      virus inactivation. Reduced reverse transcriptase-dependent cDNA generation post
      entry accounts for the loss in infectivity and is likely due to a polymerase
      processivity defect. The virion-associated reverse transcription complex is thus
      photolabile. The phenomenon could be important in certain experimental
      situations, notably at elevated temperatures or when exposure to light is
      extensive. Additionally, our study suggests that the reverse transcription
      complex is a suitable target for an anti-retroviral strategy; identification of
      the nature of the lesion and the mechanism of its induction may inform the design
      of novel inhibitors.

PMID- 16099013
TI  - Mislocalization of flashes during smooth pursuit hardly depends on the lighting
      conditions.
AB  - Targets that are briefly flashed during smooth pursuit eye movements are
      mislocalized in the direction of motion (forward shift) and away from the fovea
      (spatial expansion). Hansen [Hansen, R. M. (1979). Spatial localization during
      pursuit eye movements. Vision Research 19(11), 1213-1221] reported that these
      errors are not present for fast motor responses in the dark, whereas Rotman et
      al. [Rotman, G., Brenner, E., Smeets, J. B. (2004). Quickly tapping targets that
      are flashed during smooth pursuit reveals perceptual mislocalizations.
      Experimental Brain Research 156(4), 409-414] reported that they are present for
      fast motor responses in the light. To evaluate whether the lighting conditions
      are the critical factor, we asked observers to point to the positions of flashed
      objects during smooth pursuit either in the dark or with the room lights on. In a
      first experiment, the flash, which could appear at 1 of 15 different positions,
      was always shown when the eye had reached a certain spatial position. We found a
      forward bias and spatial expansion that were independent of the target and
      ambient luminance. In a second experiment, the flash was always shown at the same
      retinal position, but the spatial position of the eye at the moment of flash
      presentation was varied. In this case we found differences between the luminance
      conditions, in terms of how the errors depended on the velocity and position on
      the trajectory. We also found specific conditions in which people did not
      mislocalize the target in the direction of pursuit at all. These findings may
      account for the above-mentioned discrepancy. We conclude that although the
      lighting conditions do influence the localization errors under some
      circumstances, it is certainly not so that such errors are absent whenever the
      experiment is conducted in the dark.

PMID- 16099014
TI  - Global shape coding for motion-defined radial-frequency contours.
AB  - The visual system is highly skilled at recovering the shape of complex objects
      defined exclusively by motion cues. But while low-level and high-level mechanisms
      involved in shape-from-motion have been studied extensively, intermediate
      computational stages remain poorly understood. In the present study, we used
      motion-defined radial-frequency contours--or motion RFs--to probe intermediate
      stages involved in the computation of motion-defined shape. Motion RFs consisted
      of a virtual circle of Gabor elements whose carriers drifted at speeds determined
      by a sinusoidal function of polar angle. Motion RFs elicited vivid percepts of
      shape, and observers could detect and discriminate radial frequencies up to
      approximately five cycles. Randomizing Gabor speeds over a small contour segment
      impaired detection and discrimination performance significantly more than
      predicted by probability summation. Threshold comparisons between spatial-RF and
      motion-RF contours ruled out that motion-induced shifts in perceived position
      (i.e., the DeValois effect) determine shape perception in motion RFs. Together,
      results indicate that the shape of motion RFs is processed by synergistic
      mechanisms that perform a global analysis of motion cues over space. These
      results are integrated with data on perceptual interactions between motion RFs
      and spatial-RFs and are discussed in terms of cue-specific and cue-invariant
      representations of object shape in human vision.

PMID- 16099015
TI  - Serifs and font legibility.
AB  - Using lower-case fonts varying only in serif size (0%, 5%, and 10% cap height),
      we assessed legibility using size thresholds and reading speed. Five percentage
      serif fonts were slightly more legible than sans serif, but the average inter
      letter spacing increase that serifs themselves impose, predicts greater
      enhancement than we observed. RSVP and continuous reading speeds showed no effect
      of serifs. When text is small or distant, serifs may, then, produce a tiny
      legibility increase due to the concomitant increase in spacing. However, our data
      exhibited no difference in legibility between typefaces that differ only in the
      presence or absence of serifs.

PMID- 16099016
TI  - Henry's law constants for hexachlorobenzene, p,p'-DDE and components of technical
      chlordane and estimates of gas exchange for Lake Ontario.
AB  - The Henry's law constants (HLC) for trans- and cis-chlordane (TC, CC), trans
      nonachlor (TN), hexachlorobenzene (HCB) and p,p'-DDE were determined by the gas
      stripping method over a temperature range of 5-35 degrees C. The HLC variation
      versus temperature (K) was described by logH=m/T+b. Parameters of this equation
      were (with standard deviations) TC: m=-1524+/-158, b=6.58+/-0.54; CC: m=-1786+/
      209, b=7.42+/-0.71; TN m=-2068+/-284, b=8.44+/-0.97; HCB: m=-3013+/-174,
      b=11.60+/-0.59 and p,p'-DDE: m=-2043+/-240, b=8.37+/-0.82. The HLCs (Pa m3 mol(
      1)) at 25 degrees C (298.15 K) were: TC=29; CC=27; TN=32; p,p'-DDE=33 and HCB=35.
      These HLCs values were used to calculate fugacity ratios from paired air and
      water data from Lake Ontario, July 1998. The resulting fugacity ratios predict
      that volatilization was occurring for all compounds during that month.

PMID- 16099017
TI  - Decolourization of synthetic dyes by Trametes hirsuta in expanded-bed reactors.
AB  - The present paper studies the decolourization of different synthetic dyes (Indigo
      Carmine, Bromophenol Blue, Methyl Orange and Poly R-478) by the white-rot fungus
      Trametes hirsuta at bioreactor scale under solid-state conditions, operating with
      ground orange peelings as a support-substrate. Dye decolourization was performed
      in both batch and continuous mode. Batch cultivation led to high decolourization
      percentages in a short time (100% for Indigo Carmine in 3h and 85% for
      Bromophenol Blue in 7 h). As for continuous cultivation, different hydraulic
      retention times (HRT) were studied (0.8, 1, 1.5 and 3d). The highest
      decolourization percentages were obtained operating at a HRT of 3d, especially
      for the dyes Methyl Orange and Poly R-478 (81.4% and 46.9%, respectively). This
      is a very interesting result, since there are few studies dealing with the
      continuous decolourization of dyes at bioreactor scale by fungal laccases.

PMID- 16099018
TI  - Lack of age-related increase of mitochondrial DNA amount in brain, skeletal
      muscle and human heart.
AB  - During the ageing process, an increase of mitochondrial DNA (mtDNA) deletions and
      other mutations have been reported. These structural alterations of mtDNA are
      assumed to cause a reduction in the respiratory chain activity and may contribute
      to the ageing process. Therefore, the question arises if the accumulation of
      deleted mtDNA is compensated in vivo by an increase of mtDNA synthesis via a
      feedback mechanism. We designed two human mtDNA-specific oligonucleotide probes
      for quantitative mtDNA analysis of 5 different tissues from 50 individuals aged
      from 8 weeks to 93 years. The amount of mtDNA was approximately 1.1 +/- 0.5%
      (4617 +/- 2099 copies) in the caudate nucleus, 1.0 +/- 0.5% (4198 +/- 2099
      copies) in the frontal lobe cortex, 0.3 +/- 0.2% (1259 +/- 840 copies) in the
      cerebellar cortex, 1.0 +/- 0.4% (4198 +/- 1679 copies) in skeletal muscle and
      2.2+/-1.3% (9235 +/- 5457 copies) in heart muscle. We did not observe any
      significant change in the absolute copy number during ageing in five different
      tissues, and therefore, found no evidence for the postulated feedback mechanism.
      Our study indicates that mtDNA copy number is tissue-specific and depends on the
      energy demand of the tissue.

PMID- 16099019
TI  - Development of metastatic endometrial endometrioid adenocarcinoma while on
      progestin therapy for endometrial hyperplasia.
AB  - BACKGROUND: Conservative treatment with progestins is a reasonable treatment
      option for endometrial complex atypical hyperplasia and, in the experimental
      setting, for some women with grade 1 endometrial endometrioid adenocarcinoma. The
      risk of progression to a high-stage endometrial cancer is quite low, with only
      two previously reported cases in the English literature. CASE: A 40-year-old
      woman with endometrial complex atypical hyperplasia diagnosed by dilatation and
      curettage was managed conservatively with progestin therapy (initially,
      megesterol acetate; then, a combination oral contraceptive). More than 2 years
      after her original diagnosis, she developed endometrial endometrioid
      adenocarcinoma, FIGO grade 2, with lymph node metastasis. The tumor was
      microsatellite instability-high due to methylation of MLH1 and loss of MLH1
      protein. CONCLUSION: Currently, there are no good criteria for predicting which
      patients with complex atypical hyperplasia/grade 1 endometrioid adenocarcinoma
      will optimally respond to progestin therapy. There is some evidence that
      endometrial complex hyperplasia demonstrating loss of MLH1 protein by
      immunohistochemistry is strongly related to subsequent or concurrent endometrial
      cancer, especially tumors of higher grade and stage. In a woman with a biopsy
      diagnosis of endometrial hyperplasia, evaluation of MLH1 protein status by
      immunohistochemistry may provide useful information when medical management is
      being considered.

PMID- 16099020
TI  - Detection and quantitation of human papillomavirus type 16, 18 and 52 DNA in the
      peripheral blood of cervical cancer patients.
AB  - OBJECTIVE: To prospectively evaluate the feasibility of detecting human
      papillomavirus (HPV) type 16, 18 and 52 DNA in the peripheral blood of patients
      with cervical cancer using real-time polymerase chain reaction (PCR) and to
      determine its prognostic importance. METHODS: Blood and cervical swab specimens
      from 135 consecutive patients with 60 invasive cervical cancers, 10
      microinvasions, 20 cervical intraepithelial neoplasias (CIN) III, 10 CIN II, 10
      CIN I and 25 controls were collected and examined for HPV type 16, 18 and 52 DNA
      using real-time PCR to investigate the prevalence and viral load of HPV DNA at
      the time of diagnosis and during follow-up in patients with positive blood
      samples. RESULTS: Of the 60 patients with invasive cervical cancer, 27% had
      positive test results for HPV DNA in blood samples in contrast to 0% of patients
      with microinvasions, CIN III, CIN II, CIN I and normal controls. The DNA
      detection rates of viral subtypes in blood samples of cervical cancer patients
      were 5% for HPV-16, 16.7% for HPV-18, 8.3% for HPV-52, 1.7% for both HPV-16 and
      HPV-18 and 1.7% for both HPV-18 and HPV-52, while the detection rates in cervical
      swab specimens were 36.2% for HPV-16, 15.5% for HPV-18 and 17.2% for HPV-52.
      During follow-up, 8 of 10 cervical cancer patients with viral DNA detected in
      blood within 3 months after treatment had recurrence, and a high percentage
      (87.5%, 7/8) of this recurrence involved distant metastases. CONCLUSIONS: In this
      study, real-time PCR detected HPV-16, -18 or -52 DNA in the peripheral blood of
      more than one-fourth of invasive cervical cancer patients. The association
      between risk of cancer recurrence and the amount of viral DNA detected in blood
      among cervical cancer patients after treatment is intriguing and deserves further
      investigation.

PMID- 16099021
TI  - Priming with BTCP, a dopamine reuptake blocker, reinstates cocaine-seeking and
      enhances cocaine cue-induced reinstatement.
AB  - N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP), a potent dopamine
      reuptake inhibitor, substitutes for the reinforcing effects of cocaine and meets
      other criteria for possible agonist pharmacotherapeutic potential. The purpose of
      this study was to determine (1) whether BTCP modifies reinstatement of cocaine
      seeking elicited by cocaine-related environmental stimuli and (2) whether this
      compound produces priming effects. Male Wistar rats were trained to associate
      discriminative stimuli (S(D)) with cocaine availability (0.25 mg/infusion) versus
      non-reward and then were subjected to repeated extinction sessions during which
      the reinforcer and S(D) were withheld. Subsequent presentation of the cocaine
      S(D) produced recovery of cocaine-seeking. BTCP (2.5-30 mg/kg; i.p.) did not
      attenuate the conditioned reinstatement induced by the cocaine S(D) but, rather,
      potentiated this effect at 10 mg/kg. To test whether BTCP, by itself, exerts
      priming effects, different groups of rats were trained to self-administer cocaine
      (0.25 mg/infusion) for 2 weeks. After a 2-week extinction period, BTCP (5, 10 and
      20 mg/kg, i.p.) reinstated cocaine-seeking, showing that BTCP not only increases
      cocaine-seeking induced by cocaine-related stimuli but also produces priming
      effects following abstinence. The results suggest that, in cocaine abstinent
      rats, BTCP produces cocaine-like effects.

PMID- 16099022
TI  - Scheduled access to ethanol results in motor impairment and tolerance in female
      C57BL/6J mice.
AB  - We recently reported a method where water-restricted mice were given scheduled
      access to ethanol followed by access to water. C57BL/6J mice would repeatedly
      self-administer ethanol in amounts that produced high and stable blood ethanol
      concentrations (BEC) [Finn DA, Belknap JK, Cronise K, Yoneyama N, Murillo A,
      Crabbe JC. A procedure to produce high alcohol intake in mice. Psychopharmacol
      2005;178:471-480]. The studies reported here demonstrate that behavioral signs of
      motor impairment result from these high alcohol intakes, and that there was some
      evidence of tolerance development across repeated sessions. Female C57BL/6J mice
      were allowed 30 min access to ethanol (5% v/v) followed by 2.5 h access to water
      either: every 3rd day for 12 days; every 2nd day for 28 days; or every 2nd day
      for 9 days. On intervening days, mice had 3 h access to water. A control group
      had daily access to water only. Mice consumed 2-2.5 g/kg ethanol in 30 min,
      resulting in BECs of 1.4-1.5 mg/ml. Motor impairment was assessed using the
      accelerating or fixed speed rotarod, balance beam or screen test. In all studies,
      mice were tested for motor impairment immediately after 30 min access to ethanol
      or water. In Experiment 1, ethanol-exposed mice had shorter latencies to fall
      from the fixed speed rotarod and more foot slips on the balance beam than the
      control group, indicating motor impairment. After drinking ethanol, mice also
      fell from a screen more quickly than during sober pretraining. In Experiment 2,
      mice tested (without prior training) for motor impairment and tolerance on the
      fixed speed rotarod at 6.5 and 10 RPM showed repeated motor impairment in the
      ethanol group, but did not develop tolerance. In Experiment 3, mice were first
      given rotarod training at 10 RPM. Following each fluid access period, performance
      was impaired in mice self-administering ethanol at 10, but not 15 RPM, when
      compared to control mice. There was no evidence of tolerance across days.
      However, on the last day, all mice were tested at both RPM following an i.p.
      injection of 2 g/kg ethanol. Ethanol-experienced mice were less impaired at both
      RPM than the ethanol-naive mice, indicating tolerance development according to
      this between-groups index. These results suggest that C57BL/6J mice will
      repeatedly consume alcohol in amounts that produce motor impairment under these
      scheduled fluid access conditions, and that a modest degree of tolerance can be
      detected using appropriate tests.

PMID- 16099023
TI  - When phonology fails: orthographic neighbourhood effects in dyslexia.
AB  - Both cerebral hemispheres contain phonological, orthographic and semantic
      representations of words, however there are between-hemisphere differences in the
      relative engagement and specialization of the different representations. Taking
      orthographic processing for example, previous studies suggest that orthographic
      neighbourhood size (N) has facilitatory effects in the right but not the left
      hemispheres. To pursue the nature of this asymmetric N effect, in particular
      whether there are individual differences in such specialisation, we examined N in
      a case of developmental dyslexia, FM. We first describe the nature of his
      difficulties, which are mainly severe phonological deficits. Employing the
      divided visual field paradigm with FM revealed a greater sensitivity in the right
      than in the left hemisphere to orthographic variables, with a significant
      inhibitory N effect in the left, but not right hemisphere. Such inhibition, to a
      lesser degree, was found among a group of adults with dyslexia but not among age
      matched normal readers. We argue that enhanced sensitivity to orthographic cues
      is developed in some cases of dyslexia when a normal, phonology-based left
      hemisphere word recognition processing is not achieved. The interpretation
      presented here is cast in terms of differences between people with dyslexia and
      typical readers that originate in the atypical way in which orthographic
      representations are initially set up.

PMID- 16099024
TI  - The effects of multiple script priming on word recognition by the two cerebral
      hemispheres: Implications for discourse processing.
AB  - The present study examined left (LH) and right (RH) hemisphere involvement in
      discourse processing by testing the ability of each hemisphere to use world
      knowledge in the form of script contexts for word recognition. Participants made
      lexical decisions to laterally presented target words preceded by centrally
      presented script primes (four sentences describing common situations). To examine
      the maintenance of script information across intervening text, there were six
      types of primes. These consisted of either single scripts or combinations of two
      different scripts: (1) a related script, (2) an unrelated script, (3) a related
      script+a neutral "filler," (4) a related script+an unrelated script, (5) an
      unrelated script+a related script, and (6) a neutral baseline condition. Results
      indicated that in the LH, only related scripts or related scripts preceded by
      unrelated scripts facilitated target word recognition. In contrast, the RH gained
      significant facilitation from all combinations of script primes, including
      related scripts followed by either filler materials or unrelated scripts. These
      results are consistent with the theory that the RH contributes in a critical way
      to discourse comprehension by maintaining widespread meaning activation for an
      extended period. This unique ability of the RH may be especially important for
      integrative processes needed to achieve global coherence during discourse
      processing.

PMID- 16099025
TI  - Lexical competition effects in aphasia: deactivation of lexical candidates in
      spoken word processing.
AB  - Research has shown that Broca's and Wernicke's aphasic patients show different
      impairments in auditory lexical processing. The results of an experiment with
      form-overlapping primes showed an inhibitory effect of form-overlap for control
      adults and a weak inhibition trend for Broca's aphasic patients, but a
      facilitatory effect of form-overlap was found for Wernicke's aphasic
      participants. This suggests that Wernicke's aphasic patients are mainly impaired
      in suppression of once-activated word candidates and selection of one winning
      candidate, which may be related to their problems in auditory language
      comprehension.

PMID- 16099026
TI  - Nutritional aspects of manganese homeostasis.
AB  - Manganese (Mn) is an essential mineral. It is present in virtually all diets at
      low concentrations. The principal route of intake for Mn is via food consumption,
      but in occupational cohorts, inhalation exposure may also occur (this subject
      will not be dealt with in this review). Humans maintain stable tissue levels of
      Mn. This is achieved via tight homeostatic control of both absorption and
      excretion. Nevertheless, it is well established that exposure to high oral,
      parenteral or ambient air concentrations of Mn can result in elevations in tissue
      Mn levels. Excessive Mn accumulation in the central nervous system (CNS) is an
      established clinical entity, referred to as manganism. It resembles idiopathic
      Parkinson's disease (IPD) in its clinical features, resulting in adverse
      neurological effects both in laboratory animals and humans. This review focuses
      on an area that to date has received little consideration, namely the potential
      exposure of parenterally fed neonates to exceedingly high Mn concentrations in
      parenteral nutrition solutions, potentially increasing their risk for Mn-induced
      adverse health sequelae. The review will consider (1) the essentiality of Mn; (2)
      the concentration ranges, means and variation of Mn in various foods and infant
      formulas; (3) the absorption, distribution, and elimination of Mn after oral
      exposure and (4) the factors that raise a theoretical concern that neonates
      receiving total parenteral nutrition (TPN) are exposed to excessive dietary Mn.

PMID- 16099027
TI  - Zinc prevention and treatment of alcoholic liver disease.
AB  - Alcoholic liver disease (ALD) is associated with decreases in zinc (Zn) and its
      major binding protein, metallothionein (MT), in the liver. Studies using animal
      models have shown that Zn supplementation prevents alcohol-induced liver injury
      under both acute and chronic alcohol exposure conditions. There are hepatic and
      extrahepatic actions of Zn in the prevention of alcoholic liver injury. Zn
      supplementation attenuates ethanol-induced hepatic Zn depletion and suppresses
      ethanol-elevated cytochrome P450 2E1 (CYP2E1) activity, but increases the
      activity of alcohol dehydrogenase in the liver; an action that is likely
      responsible for Zn suppression of alcohol-induced oxidative stress. Zn also
      enhances glutathione-related antioxidant capacity in the liver. At the cellular
      level, Zn inhibits alcohol-induced hepatic apoptosis partially through
      suppression of the Fas/FasL-mediated pathway. Zn supplementation preserves
      intestinal integrity and prevents endotoxemia, leading to inhibition of endotoxin
      induced tumor necrosis factor-alpha (TNF-alpha) production in the liver. Zn also
      directly inhibits the signaling pathway involved in endotoxin-induced TNF-alpha
      production. These hepatic and extrahepatic effects of Zn are independent of MT.
      However, low levels of MT in the liver sensitize the organ to alcohol-induced
      injury, and elevation of MT enhances the endogenous Zn reservoir and makes Zn
      available when oxidative stress is imposed. Zn has a high potential to be
      developed as an effective agent in the prevention and treatment of ALD.

PMID- 16099028
TI  - Analyses of multilayered dental ceramics subjected to biaxial flexure tests.
AB  - OBJECTIVES: The purpose of this study was to formulate explicitly the equation to
      relate the biaxial strength of multilayered dental ceramics to the fracture load
      for multilayered discs subjected to biaxial flexure tests. METHODS: Analytical
      modeling showed that the solutions for multilayered discs subjected to biaxial
      flexure tests could be obtained from the existing solutions for monolayered
      systems by replacing the neutral surface position and the flexural rigidity of
      monolayers with those of multilayers. Finite element analyses were performed on
      porcelain/zirconia bilayered discs subjected to piston-on-ring and ring-on-ring
      tests to verify the analytical results. RESULTS: Good agreement was obtained
      between (i) present analytical results and Roark's formulas for stresses at the
      top and the bottom surfaces of bimetallic discs subjected to bending, and (ii)
      present analytical and finite element results for porcelain/zirconia bilayered
      discs subjected to piston-on-ring and ring-on-ring tests. SIGNIFICANCE: The
      present closed-form solutions provide a basis for evaluating the biaxial strength
      of multilayered dental ceramics. Depending upon the strength of the individual
      layers and the stress distribution through the thickness of the multilayer during
      tests, cracking can initiate from any layer under tension.

PMID- 16099029
TI  - Measurement of opalescence of resin composites.
AB  - OBJECTIVES: Opalescence is an optical property, where there is light scattering
      of the shorter wavelengths of the visible spectrum, giving the material a bluish
      appearance under reflected light and an orange/brown appearance under transmitted
      light. The objective of this study was to determine the opalescence of resin
      composites with a color measuring spectrophotometer. METHODS: Colors of A2 and
      enamel or translucent shades of four resin composites and of an unfilled resin
      measured in the reflectance and transmittance modes were compared, and the
      opalescence parameter (OP) was calculated as the difference in blue-yellow
      coordinate (Deltab*) and red-green parameter (Deltaa*) between the reflected and
      transmitted colors of 1-mm thick specimens. The masking effect was calculated as
      the color difference between the color of a black background and the color of
      specimen over the black background. RESULTS: The range of OP in resin composites
      was 5.7-23.7, which was higher than that of the unfilled resin. However, there
      were significant differences among the brands and shades of the resin composites.
      SIGNIFICANCE: Opalescence varied by brand and shade of the resin composites, and
      contributed to the masking of background color along with translucency parameter.
      Some of the resin composites actually displayed opalescence.

PMID- 16099030
TI  - Dynamic and static elastic moduli of packable and flowable composite resins and
      their development after initial photo curing.
AB  - OBJECTIVE: The purpose of this study was to evaluate the dynamic (storage) shear
      modulus and the static shear modulus of elasticity of packable and flowable
      composite resins and to investigate their development after initial photo-curing.
      METHODS: Three pairs of a packable versus a flowable composite and a microfill
      composite resin were tested (Alert/Flow It, Filtek P60/Filtek Flow, Admira/Admira
      Flow, A 110). Cylindrical specimens (0.85 mm x 18 mm) were made for each
      material. All specimens were conditioned and tested dry at 21 degrees C. The
      specimens were tested at 30 min, 24h and 1 week after the end of photo curing.
      Storage shear modulus and loss tangent were determined by conducting dynamic
      torsional loading in the frequency range from 1 to 150 Hz. Static shear modulus
      measurements were made by applying a constant load (below the proportional limit
      of the materials) for 10s and recording the angular deformation of the specimens.
      Data were analyzed by ANOVA and Duncan's Post hoc test (alpha=0.05). RESULTS:
      Storage shear moduli (at 1 week measurement) ranged from 3.39 to 9.67 GPa, and
      loss tangents from 0.0735 to 0.0235; static shear moduli ranged between 2.66 and
      9.80 GPa. High values of elastic moduli and low tandelta values were obtained
      with packable composites, while low moduli values were obtained with flowable
      composites. Statistically significant (alpha=0.05) differences were recorded
      between materials of the same category. Storage time, 24h and 1 week after
      initial polymerization, resulted in significant increases in both moduli of
      elasticity. Dynamic shear storage moduli were highly correlated to the static
      ones (r(2)=0.92; P<0.05). SIGNIFICANCE: The results of the aging studies showed
      that the rigidity of these materials increases significantly even 1 week after
      the clinician turns off the curing unit.

PMID- 16099031
TI  - The influence of different core material on the FEA-determined stress
      distribution in dental crowns.
AB  - OBJECTIVES: All ceramic restorations without metal have great advantages in their
      biocompatibility and aesthetic aspects. With the introduction of new core
      materials, the cores are sufficiently strong to produce long lasting all-ceramic
      restorations; however, the stresses in the veneering porcelain could still
      determine the longevity. The objective of this study was to evaluate, by finite
      element analysis (FEA), the influence of different core materials on the stress
      distribution in dental crowns. METHODS: The model of a multi-layer all-ceramic
      crown for posterior tooth 46 produced with CAD-CAM-technology was translated into
      a three-dimensional FEA program. This crown model was made with gold, zirconia,
      and alumina-based porcelain core and their matching veneering porcelains. The
      stress distribution due to the combined influences of bite forces, residual
      stresses caused by the difference in expansion coefficient of the core material
      and the veneering porcelain, and the influence of shrinkage of the cement was
      investigated. RESULTS: Stiffer core material does not always for various reasons
      result in lower stresses in the veneering porcelain. SIGNIFICANCE: This study
      indicates that the actual distribution of the tensile stresses and the design of
      restorations must be taken into account; otherwise, the significant contribution
      of stronger and tougher core materials to the performance of all-ceramic
      restorations may be offset by the weaker veneering porcelain.

PMID- 16099032
TI  - Freeze-dried agarose scaffolds with uniaxial channels stimulate and guide linear
      axonal growth following spinal cord injury.
AB  - Although several approaches to stimulate axonal regeneration after spinal cord
      injury have succeeded in stimulating robust growth of axons into a lesion site,
      the growth is generally highly disorganized, losing the distinct arrangement of
      axonal tracts within the spinal cord. Previously described freeze-dried agarose
      scaffolds, composed of individual, uniaxial channels extending through their
      entire length, were prepared with and without recombinant Brain-Derived
      Neurotrophic Factor (BDNF) protein and tested in an adult rat model of spinal
      cord injury to determine whether regenerating axons could be guided across a site
      of injury in an organized fashion. After 1 month, both the cellular and axonal
      responses within and around scaffolds were evaluated. Scaffolds were found to be
      well integrated with host tissue, individual channels were penetrated by cells,
      and axons grew through scaffolds in a strikingly linear fashion. Furthermore, the
      regeneration was significantly augmented by the incorporation of BDNF protein
      into the walls and lumen of the scaffold. These findings clearly demonstrate that
      axonal regeneration can be organized and guided across a site of injury.

PMID- 16099033
TI  - Mathematical modeling of material-induced blood plasma coagulation.
AB  - Contact activation of the intrinsic pathway of the blood coagulation cascade is
      initiated when a procoagulant material interacts with coagulation factor XII,
      (FXII) yielding a proteolytic enzyme FXIIa. Procoagulant surface properties are
      thought to play an important role in activation. To study the mechanism of
      interaction between procoagulant materials and blood plasma, a mathematical model
      that is similar in form and in derivation to Michaelis-Menten enzyme kinetics was
      developed in order to yield tractable relationships between dose (surface area
      and energy) and response (coagulation time (CT)). The application of this model
      to experimental data suggests that CT is dependent on the FXIIa concentration and
      that the amount of FXIIa generated can be analyzed using a model that is linearly
      dependent on contact time. It is concluded from these experiments and modeling
      analysis that the primary mechanism for activation of coagulation involves
      autoactivation of FXII by the procoagulant surface or kallikrein-mediated
      reciprocal activation of FXII. FXIIa-induced self-amplification of FXII is
      insignificant.

PMID- 16099034
TI  - Microbial cellulose--the natural power to heal wounds.
AB  - Microbial cellulose (MC) synthesized in abundance by Acetobacter xylinum shows
      vast potential as a novel wound healing system. The high mechanical strength and
      remarkable physical properties result from the unique nanostructure of the never
      dried membrane. This article attempts to briefly summarize the recent
      developments and applications of MC in the emerging field of novel wound
      dressings and skin substitutes. It considers the properties of the synthesized
      material, its clinical performance, as well as progress in the commercialization
      of MC for wound care products. Efficient and inexpensive fermentation techniques,
      not presently available, will be necessary to produce large quantities of the
      polymer.

PMID- 16099036
TI  - Low-intensity pulsed ultrasound stimulates cell proliferation and proteoglycan
      production in rabbit intervertebral disc cells cultured in alginate.
AB  - Intervertebral disc degeneration, one of the major causes of low-back pain, is
      known to result from alteration in biosynthesis of proteoglycan in the disc.
      Therefore, upregulating the synthesis of proteoglycan in intervertebral disc
      cells may be one approach in treating disc degeneration. Based on the finding
      that low-intensity pulsed ultrasound stimulates proteoglycan synthesis in rat
      chondrocytes, we investigated whether low-intensity pulsed ultrasound stimulates
      biological properties of rabbit intervertebral disc cells in vitro. Nucleus
      pulposus cells and annulus fibrosus cells isolated from rabbits were cultured in
      alginate beads. Cells were stimulated for 20 min each day for 5-12 days, starting
      on the third day after seeding. An ultrasound signal consisting of a 200 micros
      burst sine wave of 0.5 MHz repeating at 1 kHz, with an intensity of 0, 7.5, 15,
      30, 60, 120 mW/cm2 spatial and temporal average, was applied. DNA and
      proteoglycan synthesis were evaluated by measuring [3H]-thymidine and [35S]
      sulfate incorporation. DNA and proteoglycan content in beads were measured by
      Hoechst 33258 dye method and dimethylmethylene blue assay. Results demonstrated
      positive effects on DNA synthesis and content, following low-intensity pulsed
      ultrasound stimulation with intensities of 7.5 and 15 mW/cm2. Furthermore,
      ultrasound stimulation significantly upregulated [35S]-sulfate incorporation and
      proteoglycan content compared to the control group, following 5 days of
      stimulation in both nucleus pulposus and annulus fibrosus cells. These findings
      suggest the possible application of low-intensity pulsed ultrasound in biological
      repair of intervertebral disc degeneration.

PMID- 16099035
TI  - Matrix inclusion within synthetic hydrogel guidance channels improves specific
      supraspinal and local axonal regeneration after complete spinal cord transection.
AB  - We have previously shown that a novel synthetic hydrogel channel composed of
      poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (pHEMA-MMA) is
      biocompatible and supports axonal regeneration after spinal cord injury. Our goal
      was to improve the number and type of regenerated axons within the spinal cord
      through the addition of different matrices and growth factors incorporated within
      the lumen of the channel. After complete spinal cord transection at T8, pHEMA-MMA
      channels, having an elastic modulus of 263+/-13 kPa were implanted into adult
      Sprague Dawley rats. The channels were then filled with one of the following
      matrices: collagen, fibrin, Matrigel, methylcellulose, or smaller pHEMA-MMA tubes
      placed within a larger pHEMA-MMA channel (called tubes within channels, TWC). We
      also supplemented selected matrices (collagen and fibrin) with neurotrophic
      factors, fibroblast growth factor-1 (FGF-1) and neurotrophin-3 (NT-3). After
      channel implantation, fibrin glue was applied to the cord-channel interface, and
      a duraplasty was performed with an expanded polytetrafluoroethylene (ePTFE)
      membrane. Controls included animals that had either complete spinal cord
      transection and implantation of unfilled pHEMA-MMA channels or complete spinal
      cord transection. Regeneration was assessed by retrograde axonal tracing with
      Fluoro-Gold, and immunohistochemistry with NF-200 (for total axon counts) and
      calcitonin gene related peptide (CGRP, for sensory axon counts) after 8 weeks
      survival. Fibrin, Matrigel, methylcellulose, collagen with FGF-1, collagen with
      NT-3, fibrin with FGF-1, and fibrin with NT-3 increased the total axon density
      within the channel (ANOVA, p<0.05) compared to unfilled channel controls. Only
      fibrin with FGF-1 decreased the sensory axon density compared to unfilled channel
      controls (ANOVA, p<0.05). Fibrin promoted the greatest axonal regeneration from
      reticular neurons, and methylcellulose promoted the greatest regeneration from
      vestibular and red nucleus neurons. With Matrigel, there was no axonal
      regeneration from brainstem motor neurons. The addition of FGF-1 increased the
      axonal regeneration of vestibular neurons, and the addition of NT-3 decreased the
      total number of axons regenerating from brainstem neurons. The fibrin and TWC
      showed a consistent improvement in locomotor function at both 7 and 8 weeks.
      Thus, the present study shows that the presence and type of matrix contained
      within synthetic hydrogel guidance channels affects the quantity and origin of
      axons that regenerate after complete spinal cord transection, and can improve
      functional recovery. Determining the optimum matrices and growth factors for
      insertion into these guidance channels will improve regeneration of the injured
      spinal cord.

PMID- 16099037
TI  - Structural characterization of bioengineered human corneal endothelial cell
      sheets fabricated on temperature-responsive culture dishes.
AB  - For the purpose of corneal regenerative medicine, we fabricated human corneal
      endothelial cell sheets on temperature-responsive dishes, which could be non
      invasively harvested as intact, transplantable sheets by simply reducing the
      culture temperature. Cells demonstrated hexagonal cell shape with numerous
      microvilli and cilia, and also exhibited abundant cytoplasmic organelles similar
      to these cells in vivo. Immunofluorescence for type IV collagen and fibronectin
      revealed that abundant extracellular matrix (ECM) was deposited on the basal
      surface throughout culture, and the deposited ECM was harvested along with the
      cell sheets by reducing culture temperature to 20 degrees C. Faint ECM remnants
      were observed on the dish surfaces after cell sheet detachment.
      Immunofluorescence for ZO-1 showed that tight junctions were established between
      cells, and immunoblotting indicated that intact ZO-1 was maintained during cell
      sheet harvest, while conventional proteolytic cell harvest methods resulted in
      the degradation of ZO-1. These results suggest that these transplantable corneal
      endothelial cell sheets can be applied to treat patients with damaged corneas.

PMID- 16099038
TI  - In situ gelling hydrogels for conformal repair of spinal cord defects, and local
      delivery of BDNF after spinal cord injury.
AB  - Permanent functional loss usually occurs after injury to the spinal cord.
      Currently, a clinical strategy to promote regeneration in the injured spinal cord
      does not exist. It has become evident that in order to promote regeneration, a
      growth permissive substrate at the injury site is critical. In this study, we
      report the utilization of an agarose scaffold that gels in situ, conformally
      filling an irregular, dorsal over-hemisection spinal cord defect in adult rats.
      Besides being growth permissive, the scaffolds also serve as carriers of trophic
      factors when embedded with BDNF releasing microtubules. We report that our thermo
      reversible scaffolds are capable of supporting 3D neurite extension in vivo and
      are effective carriers of drug delivery vehicles for sustained local delivery of
      trophic factors. We demonstrate that BDNF encourages neurite growth into the
      scaffolds, and reduces further the minimal inflammatory response agarose gels
      generate in vivo as evidenced by quantitative analysis of the extent of NF-160
      kDA positive neurons and axons, GFAP positive reactive astrocytes, and CS-56
      positive chondroitin sulfate proteoglycan at the interface of the scaffold and
      host spinal cord. We suggest that these thermo-reversible scaffolds have great
      potential to serve as growth permissive 3D scaffolds, and to present neurotrophic
      factors and potentially anti-scar agents to the injury site and enhance
      regeneration after spinal cord injury.

PMID- 16099039
TI  - Wnt and calcium signaling: beta-catenin-independent pathways.
AB  - Wnt signaling is a complex pathway in which beta-catenin is typically viewed as a
      central mediator. However, within the past 15 years, at least three Wnt-mediated
      pathways have been proposed that function independent of beta-catenin. One
      pathway involves activation of calcium/calmodulin-dependent kinase II (CamKII)
      and protein kinase C (PKC). Another includes recruitment of heterotrimeric GTP
      binding proteins to activate phospholipase C (PLC) and phosphodiesterase (PDE).
      Lastly, a pathway similar to the planar cell polarity (PCP) pathway in Drosophila
      has been identified that activates the Jun-N-terminal kinase (JNK) and, perhaps,
      small GTP-binding proteins. Calcium has been implicated as an important second
      messenger in all of these pathways. This review will focus on the role of calcium
      in Wnt signaling and, as a consequence, provide a limited overview of beta
      catenin-independent Wnt signaling.

PMID- 16099040
TI  - Contribution of capacitative and non-capacitative Ca2+-entry to M3-receptor
      mediated contraction of porcine coronary smooth muscle.
AB  - We studied the contribution of store-operated or capacitative Ca2+-entry (SOCE or
      CCE, respectively) through store-operated Ca2+ channels (SOCCs) and the
      contribution of Ca2+-entry through receptor-operated, non-selective cation
      channels (ROCCs or NSCCs, respectively), on the M3-receptor-mediated (270 nM Ach)
      contractile response of porcine coronary smooth muscle strips by means of the
      respective inhibitors. In the presence of L-VOCC blockade (1 microM verapamil),
      LOE 908 (inhibition of NSCCs) decreased the contractile response to 75+/-5%
      (p<0.01, n=6), 2-APB (inhibition of SOCCs) and SK and F 96365 (inhibition of
      SOCCs and of NSCCs) decreased the response to 45+/-4% (p<0.001, n=10) and to 23+/
      2% (p<0.001, n=5), respectively (control: Ach response in the presence of
      verapamil alone). In the absence of L-VOCC blockade, LOE 908 reduced the Ach
      response to 49+/-7% (p<0.001, n=8) and SK and F 96365 to 3+/-2% (p<0.001, n=4) of
      control, whereas 2-APB transiently increased the response (peak effect: 130+/
      11%; p<0.05, n=8). We conclude: (1) the main source of activator Ca2+ during the
      M3-receptor-mediated contractile response is the Ca2+ influx through L-VOCCs; (2)
      however, in the presence of L-VOCC blockade, the contractile response is mainly
      due to Ca2+-entry through SOCCs; (3) NSCCs may be considerably involved in M3
      receptor-mediated contraction as they may serve to depolarize the membrane
      potential and, thus, to open L-VOCCs; (4) in primary tissue of vascular smooth
      muscle, both, SOCE and Ca2+-entry through NSCCs are activated during M3-receptor
      stimulation.

PMID- 16099041
TI  - Opposing effects of aspirin and acetaminophen use on risk of adult acute
      leukemia.
AB  - Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs)
      has been hypothesized to be associated with reduced risk of hematologic cancer,
      although previous results have been inconsistent. The current study investigated
      the effects of aspirin or acetaminophen use on adult acute leukemia risk among
      169 individuals with leukemia and 676 age and sex matched hospital controls with
      non-neoplastic conditions who completed a comprehensive epidemiologic
      questionnaire. Results indicate that regular aspirin use may be associated with a
      modest decrease in leukemia risk [adjusted odds ratio (aOR), 0.84; 95% confidence
      interval (CI), 0.59-1.21]. In contrast, ever using acetaminophen was associated
      with elevated leukemia risk (aOR, 1.53; 95% CI, 1.03-2.26). Results did not
      differ between men and women. Other studies have demonstrated that acetaminophen
      is associated with transient decreases in DNA repair, and lymphocytes may be
      particularly susceptible to DNA damage, suggesting a mechanism for the elevated
      acute leukemia risk observed among acetaminophen users.

PMID- 16099042
TI  - Neural circuit changes mediating lasting brain and behavioral response to
      predator stress.
AB  - This paper reviews recent work which points to critical neural circuitry involved
      in lasting changes in anxiety like behavior following unprotected exposure of
      rats to cats (predator stress). Predator stress may increase anxiety like
      behavior in a variety of behavioral tests including: elevated plus maze, light
      dark box, acoustic startle, and social interaction. Studies of neural
      transmission in two limbic pathways, combined with path and covariance analysis
      relating physiology to behavior, suggest long term potentiation like changes in
      one or both of these pathways in the right hemisphere accounts for stress induced
      changes in all behaviors changed by predator stress except light dark box and
      social interaction. Findings will be discussed within the context of what is
      known about neural substrates activated by predator odor.

PMID- 16099043
TI  - TMT-induced autonomic and behavioral changes and the neural basis of its
      processing.
AB  - One of the main interests in the field of neuroscience is the investigation of
      the neural basis of fear. During recent years, an increasing number of studies
      have used trimethylthiazoline (TMT), a component of red fox feces, as a stimulus
      to induce fear in predator naive rats, mice, and voles. The aim of the present
      review is to summarize these studies. We present an overview to the autonomic and
      behavioral changes that are induced by TMT exposure. Then, we summarize the small
      number of studies that have examined the neural processing of the TMT stimulus.
      Finally, we compare these studies with those using a natural predator or predator
      odor to induce fear and discuss the possible use of TMT exposure in rodents as an
      animal model of unconditioned fear in humans.

PMID- 16099044
TI  - The role of CRF receptors in anxiety and depression: implications of the novel
      CRF1 agonist cortagine.
AB  - Corticotropin-releasing factor (CRF), a 41 amino acid peptide exhibits its
      actions through two pharmacologically distinct CRF receptor subtypes CRF(1) and
      CRF(2). Regulation of the relative contribution of the two CRF receptors to
      central CRF activity may be essential in coordinating physiological responses to
      stress. To facilitate the analysis of their differential involvement, we recently
      developed a CRF(1)-selective agonist cortagine by synthesis of chimeric peptides
      derived from human/rat CRF, ovine CRF, and sauvagine. Cortagine was analyzed in
      behavioral experiments using male wild type and CRF(2)-deficient C57BL/6J mice
      for its action on anxiety- and depression-like behaviors. In contrast to the
      current hypothesis that increased CRF(1) activity facilitates the expression of
      anxiety- and depression-like behavior, cortagine combines anxiogenic properties
      with antidepressant effects. In this article, we show that antidepressant effects
      are partially mediated by CRF(1) of the dorsal hippocampus. Possible pathways
      responsible for the paradoxical antidepressant effects observed after CRF(1)
      activation are discussed.

PMID- 16099045
TI  - The mesolimbic dopamine system: the final common pathway for the reinforcing
      effect of drugs of abuse?
AB  - In this review we will critically assess the hypothesis that the reinforcing
      effect of virtually all drugs of abuse is primarily dependent on activation of
      the mesolimbic dopamine system. The focus is on five classes of abused drugs:
      psychostimulants, opiates, ethanol, cannabinoids and nicotine. For each of these
      drug classes, the pharmacological and physiological mechanisms underlying the
      direct or indirect influence on mesolimbic dopamine transmission will be
      reviewed. Next, we evaluate behavioral pharmacological experiments that
      specifically assess the influence of activation of the mesolimbic dopamine system
      on drug reinforcement, with particular emphasis on animal experiments using drug
      self-administration paradigms. There is overwhelming evidence that all five
      classes of abused drugs increase dopamine transmission in limbic regions of the
      brain through interactions with a variety of transporters, ionotropic receptors
      and metabotropic receptors. Behavioral pharmacological experiments indicate that
      increased dopamine transmission is clearly both necessary and sufficient to
      promote psychostimulant reinforcement. For the other four classes of abused
      substances, self-administration experiments suggest that although increasing
      mesolimbic dopamine transmission plays an important role in the reinforcing
      effects of opiates, ethanol, cannabinoids and nicotine, there are also dopamine
      independent processes that contribute significantly to the reinforcing effects of
      these compounds.

PMID- 16099046
TI  - Changes in mussel Mytilus galloprovincialis protein profile as a reaction of
      water pollution.
AB  - In the present report the changes in mussels Mytilus galloprovincialis protein
      profile, as a reaction of water pollution, is presented. The antioxidant capacity
      was determined by the efficacy to scavenge the derived radical in mussel samples
      using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. The highest
      percentage of inhibition was estimated in protein mussels from the dirty area
      (DM) in comparison with the clean samples (CM). The amounts of both zinc and
      copper determined by atomic spectroscopy were significantly higher in the protein
      mussels from the dirty than from the clean areas (P<0.05). Fourier Transform
      Infrared (FT-IR) spectroscopy and fluorescence revealed specific qualitative
      changes in secondary and tertiary structures of mussel proteins from the dirty
      area by the shift in the amides I and II positions and fluorescence intensity.
      Estimated temperature and enthalpy of denaturation in the protein mussels well
      correlated with fluorescence and spectroscopic measurements and showed the
      changes influenced by water pollution.

PMID- 16099048
TI  - Heteroligomeric forms of codon 54 mannose binding lectin (MBL) in circulation
      demonstrate reduced in vitro function.
AB  - Mannose binding lectin (MBL) is a pattern recognition molecule that plays a
      pivotal role in innate immunity. This liver derived, circulating plasma protein
      binds organisms displaying high-density carbohydrate structures and flags them
      for destruction via opsonisation and initiation of the lectin pathway of the
      complement cascade. The present study reveals native, oligomeric forms of human
      MBL in plasma from healthy blood donors of differing genotypes and correlates the
      relative abundance of observed molecular weight species with mannan binding
      activity and C4 deposition in vitro. Wild type (A/A) individuals demonstrate
      predominately high molecular weight MBL that correlated with high mannan binding
      capacity and C4 deposition. A/C individuals demonstrated predominantly low
      molecular weight MBL with decreased mannan binding and C4 deposition activity.
      A/D individuals demonstrated both high molecular weight and low molecular weight
      MBL with reduced mannan binding and C4 deposition predominantly seen in
      combination with LX promoter. We identified A/B individuals as a unique group
      with large variation in MBL level, mannan binding activity and C4 deposition and
      propose a model for C4 deposition based on differential binding of MASP.

PMID- 16099047
TI  - Differential regulation of chromatin structure of the murine 3' IgH enhancer and
      IgG2b germline promoter in response to lipopolysaccharide and CD40 signaling.
AB  - Class switch recombination (CSR) of murine immunoglobulin heavy chain (IgH) is
      controlled by germline transcription-coupled modification of the accessibility of
      the highly repetitive switch regions (S) located upstream of the constant region
      genes. Activation of the 3' IgH enhancer (3'E) is believed to regulate CSR during
      B cell terminal differentiation, although the detailed molecular mechanism
      remains unclear. Here, we show that BAF57 and BRG1, two essential subunits of
      murine SWI/SNF complex, differentially associate with the DNase I hypersensitive
      region HS1/2 of 3'E and the IgG2b germline promoter in response to LPS activation
      or CD40 engagement. Both LPS and CD40 signaling cause SWI/SNF complex to
      dissociate from HS1/2 and associate with their responsive IgG2b germline
      promoter, suggesting the potential fluidity of chromatin structure and specific
      regulatory mode for the ATP-dependent chromatin remodeler during CSR. More
      interesting, increase in histone acetylation is either inverse or parallel with
      the action of SWI/SNF complex at HS1/2 enhancer or IgG2b germline promoter,
      respectively. Chromatin immunoprecipitation experiments show that alteration of
      histone H3 and H4 acetylation has overall similarities in response to LPS and
      CD40 signaling, with H3 hyperacetylated and H4 hypoacetylated at the HS1/2
      enhancer and reversed modification patterns at the IgG2b germline promoter.
      Finally, the specificity of LPS and CD40 signaling in control of CSR could be
      partially coded by the specific acetylation marking of H3 and H4. Our results
      further strengthen the notion that chromatin remodeling plays a critical role in
      CSR.

PMID- 16099049
TI  - Combinatorial discovery of new asymmetric cis platinum anticancer complexes is
      made possible with solid-phase synthetic methods.
AB  - To efficiently access asymmetric cis platinum (II) complexes for biological
      evaluation, a new solid-phase synthesis was designed. This synthesis was used for
      the preparation of a small library of platinum compounds. Several compounds from
      this library revealed promising activity during a cytotoxicity screen. Two active
      compounds were, therefore, synthesised on a larger scale and tested more
      extensively against a larger panel of cell-lines, confirming their high potential
      as antitumour compounds. The work presented illustrates how a combination of a
      new methodology and established techniques can speed up the search for platinum
      complexes with improved cytotoxic profiles compared to cisplatin.

PMID- 16099050
TI  - Prognostic significance of low serum levels of Clara cell phospholipid-binding
      protein in occupational aluminium neurotoxicity.
AB  - The relationship between respiratory and neurological effects of exposure to
      aluminium (Al) was investigated in a group of foundry workers exposed to Al at
      concentrations below the threshold limit value (TLV) binding in Poland (2.0 mg
      Al2O3 m(-3)). Neurological and neurophysiological parameters indicated
      subclinical effects of Al exposure on the nervous system. The measurement of
      serum anti-inflammatory Clara cell protein (CC16) was employed as a peripheral
      marker of the lung epithelium function. There was a strong inverse relationship
      between serum Al (Al-S) and CC16 concentrations (p = 0.006). The lowest CC16
      concentrations were found in serum of workers characterised by subjective
      symptoms of the central nervous system (CNS) and abnormal results of
      neurophysiological examinations (EEG and VEP). Low serum CC16 concentrations and
      enhanced Al and iron (Fe) levels were also observed in the younger age group of
      workers with the subjective CNS symptoms and abnormal VEP results, which suggests
      that Fe is implicated in strengthening of the neurotoxic Al potential. The
      results of our study support the hypothesis that subclinical neurological
      symptoms (especially abnormal VEP) are most likely associated with
      internalisation of Al ions with lipid fractions of the lung epithelium, which in
      turn may help Al ions overcome the blood-brain barrier. Low serum CC16
      concentrations (<10 microg L(-1)) were noted in workers with the abnormal results
      of neurological (CNS) and neurophysiological (EEG and VEP) examinations as well
      as with Al body burden manifested by urinary excretion (Al-U) below 60 microg L(
      1) and Al-S concentration of 2 microg L(-1). This concentration may be considered
      as a threshold allowable biological concentration of aluminium.

PMID- 16099051
TI  - Effect of anion channel antagonists and La3+ on citrate release, Al content and
      Al resistance in maize roots.
AB  - The correlation between organic acid anion release and Al content was examined in
      two maize (Zea mays L.) inbred lines, Cat 100-6 (Al-resistant) and S 1587-17 (Al
      sensitive) treated with anion channel antagonists and La3+, a cation channel
      blocker. In the intact roots of Al-resistant maize, the Al-induced excretion of
      citrate was inhibited by the anion channel antagonists niflumic acid, anthracene
      9-carboxylic and ethacrinic acid. Citrate release in excised root apices was
      reduced by 60% in the presence of 15 microM niflumic acid, while the Al content
      increased by 42%. Nevertheless, Cat 100-6 accumulated less Al than S 1587-17 when
      the rate of citrate release was similar in both lines, indicating that other
      mechanisms of Al-resistance are operating in Cat 100-6. The presence of 60 microM
      La3+ did not change the rate of citrate release, but the Al content in excised
      root apices of Al-resistant plants was reduced by 70%. These results suggest that
      the Al distributed uniformly in the roots does not contribute to citrate release
      and possibly the activity of anion channels is correlated with the free
      activities of extracellular Al3+ close to anion channels.

PMID- 16099052
TI  - Treatment of prosthetic valve infective endocarditis due to multi-resistant Gram
      positive bacteria with linezolid.
AB  - OBJECTIVES: Clinical experience with linezolid in the treatment of infective
      endocarditis either alone or in combination with other agents is limited. We
      describe our experience in the treatment of two patients with IE due to multi
      resistant Gram-positive bacteria. METHODS: One patient with MRSE and one with VRE
      endocarditis were treated with regimens containing linezolid. The killing
      kinetics of linezolid in combination with gentamicin or vancomycin against
      isolates of Staphylococcus epidermidis and Enterococcus faecalis were analysed in
      vitro. RESULTS: Clinical response and eradication of bacteraemia was achieved
      with linezolid therapy in both patients. Time-kill curve studies showed that
      linezolid was bacteriostatic against the MRSE and VRE isolates used. Combination
      with gentamicin or vancomycin did not produce synergy or antagonism but at best
      only marginal additive effect. CONCLUSIONS: Although bacteriostatic, linezolid
      provides an important therapeutic option in IE due to multi-resistant Gram
      positive pathogens. It challenges the conventional wisdom that bactericidal
      synergy is required for the effective treatment of most cases of IE due to Gram
      positive organisms.

PMID- 16099053
TI  - Factors associated with failed and completed railway suicides.
AB  - BACKGROUND: The present analysis aimed to assess the proportion of survivors of
      railway suicides and to compare survivors and completers in terms of personal
      characteristics and temporal patterns surrounding the event, to identify
      potential differences between those who completed suicide and those who survived
      a serious suicide attempt. METHODS: A total of 5731 suicide victims (including
      4003 cases with complete documentation on sex) of the German central railway
      registry of person accidents covering a six-year observation period of 1997 to
      2002 and satisfying the operational definition of an act of suicidal behaviour
      according to the ICD-10 were included into the data set. To assess the impact of
      sex, age, local and temporal factors on case fatality, a multivariate logistic
      regression analysis was performed. RESULTS: A minority of 540 (9.4%) subjects
      survived the suicidal event leading to a fatal to non-fatal ratio of 9.6:1
      (chi(2)-test for equal proportions, p<0.001). Multivariate logistic regression
      analysis identified the following variables as risk factors for fatal outcome:
      men (vs. women: Odds ratio (OR)=2.05; 95% CI: 1.65-2.56), night (vs. day:
      OR=1.80; 95% CI: 1.43-2.27), open track (vs. station area: OR=2.95; 95% CI: 2.36
      2.67) and main railway line (vs. local railway line: OR=2.29; 95% CI: 1.43-3.68).
      Interactions between two factors on fatal outcome were multivariate tested but
      showed no significance. CONCLUSIONS: Close to 10% of all railway suicide attempts
      are nonfatal. Fatality of suicidal behaviour on railway tracks is significantly
      associated with male sex pointing to a certain degree of ambivalence. Higher odds
      to die on open track area, fast track lines and during night-time suggest a
      reduced opportunity to survive due to circumstances.

PMID- 16099054
TI  - Cells, cytokines and other molecules associated with rejection of
      gastrointestinal nematode parasites.
AB  - Infections with gastrointestinal nematodes represent a major problem for human
      health and animal health and production. The physical size of the parasite, its
      changing life-cycle stages and the relative inaccessibility to host cells pose
      unique challenges to the immune system, which has evolved specialized strategies
      for parasite control. This paper reviews the work performed in the authors'
      laboratories to identify components that are involved in the natural rejection
      response against ruminant gastrointestinal nematode parasites, in particular
      Haemonchus contortus in sheep. The results of these studies indicate that stage
      specific antibodies act in concert with effector cells, in particular globular
      leukocytes (intraepithelial mast cells) and eosinophils, appropriately
      activated/primed by type 2 (T2) cytokines, to initiate different mechanisms of
      parasite expulsion and killing. In addition, other molecules, in particular
      carbohydrate binding galectins, may be involved in strengthening the final
      effector phase of the rejection response.

PMID- 16099055
TI  - The evolution and maintenance of polymorphism in the major histocompatibility
      complex.
AB  - Lambs with the G2 allele at the ovine major histocompatibility complex (mhc)
      class II locus DRB1 has previously been shown to have lower faecal nematode egg
      counts than lambs with the I allele at this locus. This association has been
      confirmed in separate cohorts from the same farm. Other alleles within the mhc
      have also shown associations with nematode resistance in other breeds of sheep.
      Therefore, variation in the mhc is responsible for part of the observed genetic
      variation in resistance to nematode infection. In addition to the specific effect
      of particular alleles, heterozygotes are also more resistant than homozygotes.
      This heterozygote advantage is capable of maintaining the high levels of
      polymorphism observed within the mhc.

PMID- 16099057
TI  - Chromosome 5 and multiple sclerosis.

PMID- 16099056
TI  - Clonal expansion of IgA-positive plasma cells and axon-reactive antibodies in MS
      lesions.
AB  - Immunoglobulin A (IgA), the predominant immunoglobulin class in mucosal
      secretions, has been found in the cerebrospinal fluid of patients with multiple
      sclerosis (MS). In this study we examined the infiltration of clonally expanded
      IgA plasma cells in lesions of MS brains. Sequences of complementarity
      determining region 3 of IgA variable heavy chain (V(H)) genes demonstrated the
      clonal expansion of IgA-bearing plasma cells in MS lesions. Somatic mutations and
      ongoing intra-clonal mutations occurred in their V(H) genes. Immunohistochemical
      study demonstrated infiltration of dimer and polymer IgA1- and A2-positive plasma
      cells in perivascular spaces, in the parenchyma of MS lesions, and in the
      adjacent white matter. Double immunofluorescence staining showed binding of IgA
      antibody on axons and walls of microvessels in the areas of chronic active and
      inactive demyelination. Bielshowsky's silver impregnation revealed axonal damage
      in these areas. These findings suggest that IgA in the CNS are localized on axons
      in lesions and may contribute to axonal damage in MS.

PMID- 16099058
TI  - Electrosensory interference in naturally occurring aggregates of a species of
      weakly electric fish, Eigenmannia virescens.
AB  - The detection and identification of behaviorally relevant signals in the presence
      of competing signals in the environment is a major challenge of animal sensory
      systems. In weakly electric fish such as Eigenmannia virescens, the interactions
      between the autogenous electric field and the electric fields of nearby
      conspecifics can have profound effects on the perception of other behaviorally
      relevant electrosensory information. To better understand the natural signals
      that the nervous system of Eigenmannia experiences during the processing of
      electrosensory information, we examined the electrosensory milieu of Eigenmannia
      in the wild and in the laboratory. Recordings of the electric fields of
      Eigenmannia were made in 'black' and 'white' waters near the Napo River in
      eastern Ecuador. Fourier analysis revealed that Eigenmannia typically experience
      the electric fields of three to five conspecifics during the day and night in
      each habitat. The median difference in electric organ discharge frequencies
      between nearby Eigenmannia during the day was 23 Hz in black water habitats, 41
      Hz in white water, and 37 Hz at night in both habitats: these signals are known
      to activate tuberous electroreceptors and downstream CNS circuits. There was no
      correlation between the number of individual Eigenmannia detected at recording
      sites and electric organ discharge frequencies. Further, Eigenmannia apparently
      do not maximize the frequency differences between conspecifics. In laboratory
      studies fish were preferentially observed in aggregates of two fish or more.
      Aggregate sizes observed in the laboratory were similar to those in the wild.

PMID- 16099059
TI  - How to detect an electrocutaneous shock which is not delivered? Overt spatial
      attention influences decision.
AB  - Lateral shifts in overt attention have been previously shown to modulate reaction
      times to lateral electrocutaneous stimuli, as well as perception or
      unpleasantness thresholds. A response bias can play a role in the elicitation of
      these lateral differences. Therefore, the present experiment aimed at
      investigating whether eye orientation induces a decision bias in favour of the
      ipsilateral hemispace. Participants were asked whether or not they suspected
      subliminal electrocutaneous shocks, whereas no subliminal stimulation was
      actually delivered. A secondary visual task led participants to direct their eyes
      ipsi- or contralateral to the stimulated area. Differences between experimental
      conditions in the amount of subliminal shocks participants acknowledge to receive
      (number of positive responses) are thought to reflect decision biases. Low and
      high trait anxiety participants were involved. Results showed an interaction
      between the eye orientation and the tested hand. The number of positive responses
      was smaller in right-hand tests with contralateral eye orienting. This effect
      fits those described previously with real electrocutaneous stimuli. This
      interaction is related to hemispheric differences in spatial attention. In
      contrast to thresholds studies, this study failed to replicate that a lateral
      difference arises in the low but not in the high trait anxiety individuals,
      suggesting that this interaction was mostly due to the neurosensory processing of
      the electrocutaneous stimuli.

PMID- 16099060
TI  - Design and evaluation of an oligonucleotide-microarray for the detection of
      different species of the genus Kitasatospora.
AB  - An oligonucleotide-microarray method was developed for the detection of
      Kitasatospora species in soil samples. The 16S-23S rDNA internal transcribed
      spacer (ITS) sequence of these antibiotics-producing actinomycetes was applied to
      design short oligonucleotide probes. Two different 26-mers were synthesized,
      specific to each species used. Additionally, four oligonucleotide probes were
      designed to evaluate the system. The oligonucleotides were spotted onto slides of
      the ArrayTube microarray system and examined with a new silver-labeling detection
      technique. Prior to hybridization analysis, the 16S-23S rDNA were amplified by
      polymerase chain reaction both from bacterial cells and environmental samples
      using two actinomycetes specific primers containing a 5' biotin labeling. The
      type strains of eight Kitasatospora species included in this study were K.
      phosalacinea DSM 43860, K. setae DSM 43861, K. cochleata DSM 41652, K.
      cystarginea DSM 41680, K. azatica DSM 41650, K. mediocidica DSM 43929, K.
      paracochleata DSM 41656, and K. griseola DSM 43859. The actinomycetes-specific
      primers were shown to amplify the entire 16S-23S rDNA ITS region from all tested
      strains. More importantly, the described technique allows the detection of
      Kitasatospora strains from soil samples by extracting metagenomic DNA followed by
      a PCR amplification step. This indicates that the oligonucleotide-microarray
      method developed in this study is a reliable tool for the detection of
      Kitasatospora species in environmental samples.

PMID- 16099061
TI  - Amplification of DNA of Xanthomonas axonopodis pv. citri from historic citrus
      canker herbarium specimens.
AB  - Herbaria are important resources for the study of the origins and dispersal of
      plant pathogens, particularly bacterial plant pathogens that incite local lesions
      in which large numbers of pathogen genomes are concentrated. Xanthomonas
      axonopodis pv. citri (Xac), the causal agent of citrus bacterial canker disease,
      is a notable example of such a pathogen. The appearance of novel strains of the
      pathogen in Florida and elsewhere make it increasingly important to understand
      the relationships among strains of this pathogen. USDA-ARS at Beltsville,
      Maryland maintains approximately 700 herbarium specimens with citrus canker
      disease lesions up to 90 years old, originally collected from all over the world,
      and so is an important resource for phytogeographic studies of this bacterium.
      Unfortunately, DNA in herbarium specimens is degraded and may contain high levels
      of inhibitors of PCR. In this study, we compared a total of 23 DNA isolation
      techniques in combination with 31 novel primer pairs in order to develop an
      efficient protocol for the analysis of Xac DNA in herbarium specimens. We
      identified the most reliable extraction method, identified in terms of successful
      amplification by our panel of 31 primer pairs. We also identified the most robust
      primer pairs, identified as successful in the largest number of extracts prepared
      by different methods. We amplified Xac genomic sequences up to 542 bp long from
      herbarium samples up to 89 years old. Primers varied in effectiveness, with some
      primer pairs amplifying Xac DNA from a 1/10,000 dilution of extract from a single
      lesion from a citrus canker herbarium specimen. Our methodology will be useful to
      identify pathogens and perform molecular analyses of bacterial and possibly
      fungal genomes from herbarium specimens.

PMID- 16099062
TI  - A stable isotope titration method to determine the contribution of acetate
      disproportionation and carbon dioxide reduction to methanogenesis.
AB  - A novel stable isotope titration approach was developed to determine the
      contributions to total methane production made by CO(2) reduction and the
      disproportionation of acetate in anoxic environments. (13)CH(4), (12)CH(4),
      (13)CO(2) and (12)CO(2) production rates were measured in the head space of
      replicate anaerobic microcosms titrated with increasing amounts of (13)C-labelled
      substrates. The contribution of CO(2) reduction was calculated from the linear
      relationship between ratios of labelled and total CH(4) production and ratios of
      labelled and total CO(2) after the addition of (13)C-bicarbonate. In the case of
      acetoclastic methanogenesis rates of (13)CH(4) and (12)CH(4) production were
      fitted to a model based on an assumption that the relationship between the
      concentration of (13)C-labelled acetate and the rates of labelled and unlabelled
      methane production followed Michaelis-Menten kinetics. A comparison of the raw
      data with the model supported the assumption and provided both an estimate of the
      contribution of acetate to methane production and an estimate of the size of the
      indigenous acetate pool without the need to measure acetate directly. The method
      was applied to a freshwater sediment in the English Lake District where it was
      found that 66.3% (se 4.9) of methane production was due to acetate
      disproportionation and 28.9% (se 1.9) of methane production resulted from CO(2)
      reduction. This is in agreement with theoretical predictions and other empirical
      measurements of methanogenesis.

PMID- 16099063
TI  - A risk microbiological profile of the Australian red meat industry: risk ratings
      of hazard-product pairings.
AB  - A risk profile of microbial hazards across the supply continuum for the beef,
      sheep and goat meat industries was developed using both a qualitative tool and a
      semi-quantitative, spreadsheet tool, Risk Ranger. The latter is useful for
      highlighting factors contributing to food safety risk and for ranking the risk of
      various product/pathogen combinations. In the present profile the qualitative
      tool was used as a preliminary screen for a wide range of hazard-product pairings
      while Risk Ranger was used to rank in order of population health risk pairings
      for which quantitative data were available and for assessing the effect of
      hypothetical scenarios. 'High' risk hazard-product pairings identified were meals
      contaminated with Clostridium perfringens provided by caterers which have not
      implemented HACCP; kebabs cross-contaminated by Salmonella present in drip trays
      or served undercooked; meals served in the home cross-contaminated with
      Salmonella. 'Medium' risk hazard-product pairings identified were ready-to-eat
      meats contaminated with Listeria monocytogenes and which have extended shelf
      life; Uncooked Comminuted Fermented Meat (UCFM)/Salami contaminated with
      Enterohaemorrhagic E. coli (EHEC) and Salmonella; undercooked hamburgers
      contaminated with EHEC; kebabs contaminated by Salmonella under normal production
      or following final "flash" heating. Identified 'low' risk hazard-product pairings
      included cooked, ready-to-eat sausages contaminated with Salmonella; UCFM/Salami
      contaminated with L. monocytogenes; well-cooked hamburgers contaminated with
      EHEC. The risk profile provides information of value to Australia's risk managers
      in the regulatory, processing and R&D sectors of the meat and meat processing
      industry for the purposes of identifying food safety risks in the industry and
      for prioritising risk management actions.

PMID- 16099064
TI  - Amperometric biosensor for the detection of hydrogen peroxide using catalase
      modified electrodes in polyacrylamide.
AB  - A simple biosensor for the detection of hydrogen peroxide in organic solvents has
      been developed and coupled to a flow injection analysis (FIA) system. Catalase
      was entrapped in polyacrylamide gel and placed on the surface of platinum
      (working electrode) fixed in a Teflon holder with Ag-wire (auxiliary electrode),
      followed by addition of filter paper soaked in KCl. The entrapped catalase gel
      was held on the electrode using membranes. The effects of cellulose and
      polytetrafluroethylene (PTFE) membranes on the electrode response towards
      hydrogen peroxide have been studied. The modified electrode has been used to
      study the detection of hydrogen peroxide in solvents like water, dimethyl
      sulfoxide (DMSO), and 1,4-dioxane using amperometric techniques like cyclic
      voltammetry (CV) and FIA. The CV of modified catalase electrode showed a broad
      oxidation peak at -150 mV and a clear reduction peak at -212 mV in the presence
      of hydrogen peroxide. Comparison of CV with hydrogen peroxide in various solvents
      has been carried out. The electrode showed an irreversible kinetics with DMSO as
      the solvent. A flow cell has been designed in order to carry on FIA studies to
      obtain calibration plots for hydrogen peroxide with the modified electrode. The
      calibration plots in several solvents such as water, dimethyl sulfoxide, 1,4
      dioxane have been obtained. The throughput of the enzyme electrode was 10
      injections per hour. Due to the presence of membrane the response time of the
      electrode is concentration dependent.

PMID- 16099065
TI  - Hydrolase-catalyzed Michael addition of imidazoles to acrylic monomers in organic
      medium.
AB  - Hydrolase-catalyzed Michael addition of imidazole derivatives to acrylic monomers
      in organic medium was described. A serial of N-substituted imidazole derivatives
      were successfully synthesized in moderate yields by the catalysis of hydrolases
      in organic medium. Nine commercially available hydrolases from different sources
      were screened and all of them were found to be able to catalyze this type of
      addition reaction. The reaction yields depended on the solvent properties and the
      solvents with higher log P value supported this enzyme-catalyzed reaction to give
      higher conversion. Influence of the structure of the Michael acceptor and donor
      on the enzymatic Michael addition was also investigated. The acceptor with
      shorter alcohol chain afforded a higher yield. A more rapid conversion was
      observed when the donor had an electron-withdrawing group. This hydrolase
      catalyzed Michael addition reaction has widened the applicability of biocatalysts
      in organic and bioorganic synthesis.

PMID- 16099066
TI  - Genetic stability determinants of temperature sensitive, live attenuated
      respiratory syncytial virus vaccine candidates.
AB  - An intranasally delivered, live attenuated, temperature sensitive (ts)
      respiratory syncytial virus vaccine candidate, rA2cp248/404/1,030DeltaSH,
      exhibits a low level of genetic instability in clinical studies, in contrast to
      the relatively high stability of two similar candidates, cpts248/404 and
      rA2cp248/404DeltaSH. The latter strains, containing two ts mutations (248ts and
      404ts), are partially growth restricted at 37 degrees C, whereas,
      rA2cp248/404/1,030DeltaSH contains an additional ts mutation (1,030ts) that
      increases attenuation and partially restricts virus growth at 35 degrees C. Since
      the maximum human airway temperature is 35.5 degrees C, we investigated whether
      growth restriction at 35 degrees C contributes to genetic instability of
      rA2cp248/404/1,030DeltaSH in vitro. We conducted in vitro passage studies with
      the three strains at 32 degrees C (a fully permissive growth temperature) and 35
      degrees C (restrictive for only rA2cp248/404/1,030DeltaSH). Instability of the ts
      phenotype was observed only in rA2cp248/404/1,030DeltaSH passaged at 35 degrees
      C, and corresponded with reversion at the 248ts or 1,030ts mutation sites, as
      observed in clinical studies. This study indicates that ts mutations that
      partially restrict replication at physiologic temperatures may contribute to
      genetic instability of viruses in vivo. In vitro passage studies performed at
      appropriate temperatures can be used to assess genetic stability and to
      prioritize ts vaccine candidates for clinical evaluation.

PMID- 16099067
TI  - Partial reconstitution of hepatitis C virus RNA polymerization by heterologous
      expression of NS5B polymerase and template RNA in bacterial cell.
AB  - The hepatitis C virus (HCV) is a major etiological agent causing chronic
      hepatitis in humans. Since the virus does not grow in a cell culture, the direct
      measurement of viral replication is impossible. Therefore, the current study
      presents a surrogate model system using a viral polymerase and RNA template. A
      plasmid expressing the HCV NS5B polymerase was maintained with a plasmid
      containing a reporter gene in an Escherichia coli cell. The reporter construct
      contained the HCV 5' untranslated region (UTR) followed by a luciferase gene with
      a specific orientation so that a minus-sense transcript containing the luciferase
      fused to the 5' UTR was produced after the initial transcription. When the HCV
      NS5B polymerase was expressed in the same cell, the primary transcript was
      recognized by the polymerase due to the presence of the minus-sense 5' UTR, and a
      secondary transcript containing a plus-sense luciferase gene was produced. Thus,
      a simple luciferase assay was able to measure the HCV NS5B polymerase activity.
      The production of minus- and plus-sense transcripts was confirmed by an RT-PCR,
      while the production of HCV NS5B and expression of the reporter luciferase in the
      bacterial cell were confirmed by immunofluorescence microscopy. The
      polymerization occurred in the absence of any other viral/host factors.
      Accordingly, this would appear to be the first study to demonstrate that the
      heterologous expression of an animal viral RNA polymerase and its template in a
      bacterial cell can partially reconstitute the polymerization reaction.

PMID- 16099068
TI  - Augmented humoral and cellular immune responses to hepatitis B DNA vaccine
      adsorbed onto cationic microparticles.
AB  - Plasmid expressing HBV small envelope antigen was formulated with poly(lactide-co
      glycolide-acid) (PLGA) and cetyltrimethylammonium bromide (CTAB) to generate
      highly uniform microparticles. Controlled release of DNA from these
      microparticles was demonstrated in vitro and in vivo using flow cytometry and
      confocal laser scanning microscopy with the focus on localization and
      quantitatively evaluation of antigen-presenting cells (APCs) involved in the
      expression of target antigen. Compared to mice vaccinated with naked DNA, mice
      immunized with PLGA-CTAB-DNA microparticles displayed a much higher percentage of
      CD11c+, HBsAg-expressing APCs in the draining lymph nodes at 24 h and day 14
      postinoculation. In addition, a prolonged transcription of plasmid DNA was
      detected by RT-PCR in mice immunized with the microparticles. A significantly
      enhanced immunogenicity of PLGA-CTAB-DNA over naked DNA was observed in immunized
      mice, including higher levels of antibody production, interferon gamma (IFN
      gamma) secretion and cytotoxic T lymphocyte activity. Mice immunized with PLGA
      CTAB-DNA microparticles also showed greater efficacy of immunoprotection against
      challenge of transplanted HBsAg-expressing tumor cells. Our data suggest that
      controlled release of the PLGA-CTAB-DNA microparticles might involve in the
      mechanisms of its augmented immunogenicity and enhanced immunoprotection.

PMID- 16099069
TI  - Timing and mechanism of ancient vertebrate genome duplications -- the adventure
      of a hypothesis.
AB  - Complete genome doubling has long-term consequences for the genome structure and
      the subsequent evolution of an organism. It has been suggested that two genome
      duplications occurred at the origin of vertebrates (known as the 2R hypothesis).
      However, there has been considerable debate as to whether these were two
      successive duplications, or whether a single duplication occurred, followed by
      large-scale segmental duplications. In this article, we review and compare the
      evidence for the 2R duplications from vertebrate genomes with similar data from
      other more recent polyploids.

PMID- 16099070
TI  - Expression of agouti-related peptide, neuropeptide Y, pro-opiomelanocortin and
      the leptin receptor isoforms in fetal mouse brain from pregnant dams on a protein
      restricted diet.
AB  - Expression of agouti-related peptide, neuropeptide Y, pro-opiomelanocortin and
      leptin receptor isoforms were found in fetal mouse brain at embryonic day 12
      (E12). Levels of expression for these genes were altered in brains of E12 fetuses
      from pregnant dams on a protein-restricted diet, suggesting that the fetal brain
      is responsive to changes in maternal nutrition prior to birth.

PMID- 16099071
TI  - Two-dimensional distribution of microbial activity and flow patterns within
      naturally fractured chalk.
AB  - The two-dimensional distribution of flow patterns and their dynamic change due to
      microbial activity were investigated in naturally fractured chalk cores. Long
      term biodegradation experiments were conducted in two cores ( approximately 20 cm
      diameter, 31 and 44 cm long), intersected by a natural fracture. 2,4,6
      tribromophenol (TBP) was used as a model contaminant and as the sole carbon
      source for aerobic microbial activity. The transmissivity of the fractures was
      continuously reduced due to biomass accumulation in the fracture concurrent with
      TBP biodegradation. From multi-tracer experiments conducted prior to and
      following the microbial activity, it was found that biomass accumulation causes
      redistribution of the preferential flow channels. Zones of slow flow near the
      fracture inlet were clogged, thus further diverting the flow through zones of
      fast flow, which were also partially clogged. Quantitative evaluation of
      biodegradation and bacterial counts supported the results of the multi-tracer
      tests, indicating that most of the bacterial activity occurs close to the inlet.
      The changing flow patterns, which control the nutrient supply, resulted in
      variations in the concentrations of the chemical constituents (TBP, bromide and
      oxygen), used as indicators of biodegradation.

PMID- 16099072
TI  - Antimicrobial effect of surgical masks coated with nanoparticles.
AB  - This study assessed the antimicrobial activity of nanoparticles (consisting of a
      mixture of silver nitrate and titanium dioxide) and nanoparticle-coated facemasks
      to protect against infectious agents. The minimum inhibitory concentrations of
      the nanoparticles against Escherichia coli and Staphylococcus aureus were 1/128
      and 1/512, respectively. The antibacterial activity of nanoparticle-coated masks
      was quantified according to the procedures of AATCC 100-1999. A 100% reduction in
      viable E. coli and S. aureus was observed in the coated mask materials after 48 h
      of incubation. Skin irritation was not observed in any of the volunteers who wore
      the facemasks. Nanoparticles show promise when applied as a coating to the
      surface of protective clothing in reducing the risk of transmission of infectious
      agents.

PMID- 16099073
TI  - Isolation of pathogenic Legionella species and legionella-laden amoebae in dental
      unit waterlines.
AB  - Legionella released into the air during treatment are a potential source of
      infection. Water stagnation in dental unit waterlines (DUWLs) creates biofilms
      and promotes the proliferation of these micro-organisms. This study investigated
      the presence of amoeba infected with legionella, L. pneumophila and other
      pathogenic Legionella species in a dental teaching hospital. Water samples were
      collected in the morning and afternoon from 99 dental units and 16 taps connected
      to the municipal water supply. Samples were plated on selective media and tested
      for legionella using the direct immunofluorescent antibody technique and the
      latex agglutination test. Legionella were found in 33% of the DUWLs and in 47% of
      the mains taps supplying these units. Legionella-laden amoebae occurred in one
      mains tap sample and in 20% of DUWLs in a clinic of the teaching hospital. L.
      micdadei was the predominant species isolated from this clinic. L. pneumophila
      serogroups 2-14 predominated in the mains water, whereas L. pneumophila serogroup
      1 was found in approximately half of the contaminated DUWLs and mains taps
      irrespective of the time of sampling. Pathogenic Legionella species seeded by
      municipal water into DUWLs is a potential source of legionella infection for both
      dental personnel and patients during prolonged dental treatment. This problem is
      compounded by the presence of legionella-laden amoebae which may contain levels
      of organism well within the infective dose. The interaction of legionella with
      amoebae is an important ecological factor that may significantly increase the
      risk of legionellosis, and thus should be given further consideration in the
      refinement of risk assessment models.

PMID- 16099074
TI  - Optimization of anabaenopeptin extraction from cyanobacteria and the effect of
      methanol on laboratory manipulation.
AB  - Anabaenopeptins are commonly occurring bioactive peptides of cyanobacterial
      origin. Cyanobacteria (blue-green algae) are known to be capable of producing a
      large number of biologically active peptides, but the widespread occurrence of
      anabaenopeptins in particular, makes them ideal candidates for investigating the
      reasons that cyanobacteria produce such a complex spectrum of peptides and the
      wider implications of their natural function(s). Despite the identification of
      these peptides in cyanobacterial samples, little is known about the
      concentrations produced. For this reason, methods for the quantitative extraction
      of anabaenopeptins from lyophilized cyanobacterial cells were optimized. Higher
      yields of anabaenopeptins were obtained using aqueous methanol extraction than
      using water alone. However, repeat extractions using 50, 70 or 90% aqueous
      methanol did not result in significantly different total yields of the
      anabaenopeptin variants, ABPN-A and -B. Similarly, little difference was found in
      the quantification of purified ABPN-A and -B by high performance liquid
      chromatography with photodiode array detection (HPLC-PDA) when analyzed in
      methanol solutions of different concentrations. The effects of solvent
      concentration on the laboratory handling of ABPN-A and -B in glass and plastic
      containers were also investigated. Significantly lower concentrations of
      dissolved ABPN-A and -B were found when aqueous solutions came into contact with
      plastics, but not 50 or 100% methanol.

PMID- 16099075
TI  - Proteomic identification of proteins specifically oxidized in Caenorhabditis
      elegans expressing human Abeta(1-42): implications for Alzheimer's disease.
AB  - Protein oxidation has been shown to lead to loss of protein function, increased
      protein aggregation, decreased protein turnover, decreased membrane fluidity,
      altered cellular redox poteintial, loss of Ca2+ homeostaisis, and cell death.
      There is increasing evidence that protein oxidation is involved in the
      pathogenesis of Alzheimer's disease and amyloid beta-peptide (1-42) has been
      implicated as a mediator of oxidative stress in AD. However, the specific
      implications of the oxidation induced by Abeta(1-42) on the neurodegeneration
      evident in AD are unknown. In this study, we used proteomic techniques to
      identify specific targets of oxidation in transgenic Caenorhabditis elegans (C.
      elegans) expressing human Abeta(1-42). We identified 16 oxidized proteins
      involved in energy metabolism, proteasome function, and scavenging of oxidants
      that are more oxidized compared to control lines. These results are discussed
      with reference to Alzheimer's disease.

PMID- 16099076
TI  - [Bickerstaff's brainstem encephalitis].
AB  - INTRODUCTION: Bickerstaff's brainstem encephalitis represents a differential
      diagnostic that must be discuss with meningoencephalitis with ophtalmoplegia,
      ataxia and confusion. EXEGESE: A 26 year-old woman presented a Bickerstaff
      syndrome. A severe disturbance of consciousness had lead to admission in
      intensive care unit with mechanical ventilation. Electrophysiological tests and
      the brain magnetic resonance were normal. We have not observed systemic anti-G1Qb
      antibody in our patient. Nevertheless, 66% of patients with Bickerstaff syndrome
      have anti-GQ1b antibody during the acute phase period. We observed a beneficial
      effect of IV Ig treatment although no significant improvement was observed with
      corticosteroids. CONCLUSION: Controlled clinical trials are needed to established
      the efficacy of IV Ig or plasmapheresis as a specific therapy for this pathology.

PMID- 16099077
TI  - Professional doctorate and professional nursing practice.
AB  - The professional doctorate degree in nursing is a novel approach to gaining a
      doctoral qualification other than the traditional Doctor of Philosophy (PhD)
      degree. This taught programme aims at linking theory and practice innovations in
      addressing clinical nursing problems. This paper outlines the evolution of the
      professional doctorate in the USA, the UK and Australia and its differences from
      the traditional PhD. I argue that nurses enrolled in this course work programme
      will not only have the opportunity to pursue studies at the doctoral level, but
      it will also facilitate nurses to challenge and share their experiences in
      solving practice problems in a collegial manner. By understanding the broader
      perspective of an environment dominated by scarce resources and intricate socio
      political relationship, nurses will be able to influence policy decisions and
      ultimately improve the standard of health care and enhance the professional
      status of nursing. It may even reduce the antagonism of the anti-intellectual
      environment of the workplace through practice-oriented research.

PMID- 16099078
TI  - Intussusception and rotavirus vaccines.
AB  - The association between the first oral rotavirus vaccine to be licensed in the
      U.S. (Rotashield) and intussusception has presented a major challenge to the
      effort to reduce the global burden related to rotavirus infection. Although the
      risk of developing intussusception following immunization with Rotashield is low,
      debate continues about the estimation of intussusception risk and the events
      surrounding the withdrawal of the vaccine. The experience with Rotashield has
      highlighted the wisdom of parallel clinical trials in developing and developed
      countries and the value of post-licensure surveillance for the detection of
      uncommon adverse events. This review retraces the steps leading up to the
      withdrawal of the Rotashield vaccine and reflects on how this experience has
      influenced the development of other rotavirus vaccines.

PMID- 16099079
TI  - Costs of running a universal adolescent hepatitis B vaccination programme.
AB  - In the first UK study to examine feasibility and acceptability of universal
      adolescent hepatitis B vaccination, the costs associated with the administration
      and uptake (80.2 and 89.3% for three doses and at least two doses, respectively),
      of a three-dose regimen in pupils in Glasgow schools (2001/2002) were measured.
      These data were used to estimate the economic outlay for the delivery of a
      routine, ongoing three-dose and two-dose hepatitis B vaccine programme in
      schools. Vaccine, accounting for almost 70% of the overall costs, was the largest
      cost item for both the pilot and routine programmes, using either regimen.
      However, the ongoing, two-dose regimen was the cheapest option in this analysis,
      irrespective of vaccine price. Cost data from this study may be useful for other
      countries wishing to implement a similar programme.

PMID- 16099081
TI  - Radiobiological monitoring of striped field mouse populations in the Moscow
      recreation forest "Kuzminki".
AB  - The results of radiometric and haematological studies of striped field mice
      (Apodemus agrarius) sampled over the years 1995-2003 from the territory of the
      preserved radioactive waste burial (RWB), which is located in the Moscow
      recreation forest "Kuzminki", are presented and discussed in the paper. It was
      shown that the level of 90Sr-90Y content in mice sampled from the RWB area varies
      within the range of 0-1200 Bq/kg with an average of 98.7+/-21.5 Bq/kg. The
      content of 90Sr-90Y in the body of 80% of the mice sampled from the RWB area was
      below 100 Bq/kg. Only in 4% of the sampled mice, the 90Sr-90Y specific
      radioactivity was above 300 Bq/kg. Haematological indications of the animals
      sampled from the RWB area were within the range of normal physiological
      fluctuations. Nevertheless, a slight but statistically significant increase in
      the average amount of erythrocytes and the average percentage of banded
      neutrophils was registered in peripheral blood of the mice.

PMID- 16099080
TI  - Enhanced mucosal and systemic immune response with intranasal immunization of
      mice with HIV peptides entrapped in PLG microparticles in combination with Ulex
      Europaeus-I lectin as M cell target.
AB  - The predominant route of HIV infection is through the sexual transmission via M
      cells. Most of the peptide and protein vaccines show poor transport across the
      epithelial barrier and are commonly administered by parenteral route. In the
      present study four HIV peptides from envelope (gp 41-LZ (leucine zipper), gp 41
      FD (fusion domain) and gp120-C2) and regulatory (Nef) region in poly lactic-co
      glycolide (PLG) micro-particle delivery were evaluated in mice of outbred and
      with different genetic background to compare immune response versus MHC
      restriction. Out of the combinational and single routes of immunization
      attempted, the single route maintained the IgG, IgA and sIgA in sera and washes
      for longer duration as compared to combinational routes in which the response was
      declined. The study demonstrated that single intranasal immunization offered
      significantly higher immune response (p<0.05) over oral and rectal mucosal routes
      in terms of inducing systemic as well as mucosal response. Also, the specific
      activity measurement of IgA and IgG in sera and sIgA in washes were correlating
      to the antibody titers. However, the intramuscular route of immunization
      generated systemic response only. The entrapment of plant lectin UEA-1 a ligand
      specific for M cells in micro-particle further enhanced the immune response in
      all the mucosal routes. The IgG isotypes generated were of IgG1 and IgG2a/2b in
      sera for all the peptides. The T cell proliferation response study with and
      without UEA-1 lectin in micro-particles showed significantly high (p<0.05)
      stimulation index (SI) with intranasal immunization for all the peptides from
      cells collected from spleen (SP), peyer's patches (PP) and lamina propria (LP)
      with SI in the order LP cells>PP>or=SP. The cytokine measurement profile of IL-2,
      IFN-gamma and IL-6 and low levels of IL-4 in the cultural supernatants of SP, PP
      and LP showed mixed CD4(+) Th1 and Th2 immune response. The p24 assay showed high
      percent inhibition of HIV-IIIB virus with sera and washes obtained from
      intranasal route. Thus, overall the study highlighted the combination of UEA-1
      lectin with HIV peptides in micro-particles through intranasal immunization
      generated systemic as well as mucosal immune response.

PMID- 16099082
TI  - In vivo loads in the medial compartment of the rabbit knee.
AB  - BACKGROUND: The compressive loads produced in the medial compartment of a rabbit
      knee during hopping are unknown, and necessary for the development of an animal
      model to study unicompartmental osteoarthritis. METHODS: In an effort to obtain
      such data, a surgical procedure was developed to insert a pressure sensor into
      the medial tibial compartment of a New Zealand white rabbit knee joint, and an
      inactive sensor of the same thickness into the lateral tibial compartment. After
      the rabbits recovered from anesthesia, contact pressure was measured as the
      rabbits hopped. FINDINGS: The average peak pressure in the medial compartment was
      60 N/cm2 (SD 16), a value that corresponds to 39% of the animals' body weight
      (range: 21-61%, SD 11%). INTERPRETATION: This is the first report of measured in
      vivo pressures associated with the load transmitted through the medial
      compartment of the skeletally mature New Zealand White rabbit, a model frequently
      used to study the progression of osteoarthritis.

PMID- 16099083
TI  - A microcosm test of adaptation and species specific responses to polluted
      sediments applicable to indigenous chironomids (Diptera).
AB  - Chironomids may adapt to pollution stress but data are confined to species that
      can be reared in the laboratory. A microcosm approach was used to test for
      adaptation and species differences in heavy metal tolerance. In one experiment,
      microcosms containing different levels of contaminants were placed in polluted
      and reference locations. The response of Chironomus februarius to metal
      contaminants suggested local adaptation: relatively more flies emerged from clean
      sediment at the reference site and the reverse pattern occurred at the polluted
      site. However, maternal effects were not specifically ruled out. In another
      species, Kiefferulus intertinctus, there was no evidence for adaptation. In a
      second experiment, microcosms with different contaminant levels were placed at
      two polluted and two unpolluted sites. Species responded differently to
      contaminants, but there was no evidence for adaptation in the species where this
      could be tested. Adaptation to heavy metals may be uncommon and species specific,
      but more sensitive species need to be tested across a range of pollution levels.
      Factors influencing the likelihood of adaptation are briefly discussed.

PMID- 16099084
TI  - Stabilization of mercury-containing wastes using sulfide.
AB  - This paper summarizes the findings of our studies on mercury stabilization using
      sulfide. Primary stabilization variables such as stabilization pH and
      sulfide/mercury molar ratio were tested. Mercury stabilization effectiveness was
      evaluated using the Toxicity Characteristic Leaching Procedure (TCLP) and the
      constant pH leaching tests. The influence of interfering ions on mercury
      immobilization was also tested. The experimental results indicate that the
      sulfide-induced treatment technology is an effective way to minimize mercury
      leaching. It was found that the most effective mercury stabilization occurs at pH
      6 combined with a sulfide/mercury molar ratio of 1. The combined use of increased
      dosage of sulfide and ferrous ions ([S]/[Hg]=2 and [Fe]/[Hg]=3 at pH=6) can
      significantly reduce interferences by chloride and/or phosphate during sulfide
      induced mercury immobilization. The sulfide-treated waste stabilization
      efficiency reached 98%, even with exposure of the wastes to high pH leachants.

PMID- 16099085
TI  - Long-run consequences of parental paid work hours for child overweight status in
      Canada.
AB  - This paper explores the connection between the labour market and child overweight
      status in Canada. The labour market is a social institution which plays a
      critical role in determining how families live their day-to-day lives, for
      example, how much time and which parts of the day are available for cooking,
      eating and exercise. Using longitudinal data from the Statistics Canada National
      Longitudinal Survey of Children and Youth, we find that a history of higher hours
      of paid work by mothers (but not fathers) is associated with a higher probability
      of being 'at risk of overweight'/overweight for children aged 6-11. The policy
      implication we draw from this work is that additional support to better enable
      parents to engage in paid work without penalty to their own health or that of
      their children is clearly warranted.

PMID- 16099086
TI  - Knox's cube imitation test: a historical review and an experimental analysis.
AB  - The cube imitation test was developed by as a nonverbal test of intelligence.
      Many variants show satisfactory reliability, but performance is correlated both
      with Verbal IQ and with Performance IQ. Performance is impaired by cerebral
      lesions but unrelated to the side of lesion. Examinees describe both verbal and
      visuospatial strategies. In a new experiment, performance was disrupted by
      concurrent random generation, manual tapping, and articulatory suppression. The
      cube imitation test is not simply a measure of the ability to retain visuospatial
      information but also depends on verbal representations as well as attentional
      capacity. Even so, the test was central to the modern appreciation that any
      adequate measure of intelligence must incorporate both verbal tests and
      performance tests.

PMID- 16099087
TI  - Ackee (Blighia sapida) hypoglycin A toxicity: dose response assessment in
      laboratory rats.
AB  - Hypoglycin A, the toxin found in the ackee fruit, has been reported in the
      literature as the causative agent in incidences of acute toxicity termed Jamaican
      vomiting sickness or toxic hypoglycemic syndrome. Hypoglycin A toxicity in this
      study was determined by feeding male and female Sprague-Dawley rats a control
      diet and ackee diets that contained 4-3840 ppm of hypoglycin. The fixed dose
      method was used to quantify the acute toxic dose of hypoglycin A and was
      determined by feeding a diet consisting of the lowest hypoglycin A concentration;
      this was increased to the next highest dose after 24h until toxicity was
      observed. The maximum tolerated dose (MTD) of hypoglycin A was determined by
      feeding rats the ackee and control diets over a 30-day period. The acute toxic
      dose for male and female rats was 231.19+/-62.5 5mg hypoglycinA/kgBW and 215.99+/
      63.33 mg hypoglycinA/kgBW, respectively. This was considerably greater than the
      dose of 100 mg hypoglycin/kgBW reported in a previous study when aqueous
      hypoglycin was administered orally. The MTD of hypoglycin A in both male and
      female rats was 1.50+/-0.07 mg hypoglycinA/kgBW/day. These findings suggest that
      the form in which hypoglycin in ackee is administered could affect the
      toxicological properties it exhibits. Therefore, for the purpose of a hazard
      assessment, it may be best administered within the matrix of the fruit, which is
      the form that humans consume it.

PMID- 16099088
TI  - BDNF function in adult synaptic plasticity: the synaptic consolidation
      hypothesis.
AB  - Interest in BDNF as an activity-dependent modulator of neuronal structure and
      function in the adult brain has intensified in recent years. Localization of BDNF
      TrkB to glutamate synapses makes this system attractive as a dynamic, activity
      dependent regulator of excitatory transmission and plasticity. Despite individual
      breakthroughs, an integrated understanding of BDNF function in synaptic
      plasticity is lacking. Here, we attempt to distill current knowledge of the
      molecular mechanisms and function of BDNF in LTP. BDNF activates distinct
      mechanisms to regulate the induction, early maintenance, and late maintenance
      phases of LTP. Evidence from genetic and pharmacological approaches is reviewed
      and tabulated. The specific contribution of BDNF depends on the stimulus pattern
      used to induce LTP, which impacts the duration and perhaps the subcellular site
      of BDNF release. Particular attention is given to the role of BDNF as a trigger
      for protein synthesis-dependent late phase LTP--a process referred to as synaptic
      consolidation. Recent experiments suggest that BDNF activates synaptic
      consolidation through transcription and rapid dendritic trafficking of mRNA
      encoded by the immediate early gene, Arc. A model is proposed in which BDNF
      signaling at glutamate synapses drives the translation of newly transported (Arc)
      and locally stored (i.e., alphaCaMKII) mRNA in dendrites. In this model BDNF tags
      synapses for mRNA capture, while Arc translation defines a critical window for
      synaptic consolidation. The biochemical mechanisms by which BDNF regulates local
      translation are also discussed. Elucidation of these mechanisms should shed light
      on a range of adaptive brain responses including memory and mood resilience.

PMID- 16099089
TI  - Modulation of rotational behavior in healthy volunteers by cortisol
      administration.
AB  - Asymmetrical turning behavior is an established indicator of asymmetrical
      dopaminergic activity and thought to be a manifestation of hemispatial neglect.
      We set out to find converging support for the hypothesis that cortisol modulates
      frontal dopaminergic asymmetrical activity, and hence dopaminergically mediated
      approach behaviors, by studying the effect of cortisol administration on turning
      behavior in healthy subjects. Both when our subjects attempted to rotate through
      a target angle (twice 360 degrees) in a clockwise or anticlockwise direction with
      reduced sensory input, cortisol induced a relative clockwise turning bias.
      Furthermore, this effect interacted with scores on novelty seeking, a putative
      indicator of individual differences in dopaminergic function: subjects scoring
      higher on novelty seeking demonstrated a smaller or no increase after cortisol
      administration in their clockwise turning bias. The results provide converging
      support for the hypothesis that cortisol modulates frontal dopaminergic
      asymmetrical activity. As we discuss, they further point to the possible
      involvement of the insula in cortisol effects.

PMID- 16099090
TI  - Complete genital prolapse stage IV: surgical emergency.

PMID- 16099091
TI  - Cooperative behaviour of the elementary sarcomere units and the cross-bridge step
      size.
AB  - We present a model of muscle contraction based on purely physical grounds and
      modulated by a parameter, k, related to the visco-elastic hindrances of the
      contractile apparatus. The model predicts a strong cooperation among sarcomere
      units and proposes that viscous hindrance is a fundamental component of the
      economy of the contraction. The concept of cross-bridge step size is also
      discussed and it is concluded that the step size is of various and probably
      undeterminable length.

PMID- 16099092
TI  - Cervical spinal cord intramedullary teratoma.
AB  - We present the case of a 62-year-old patient suffering from the presence of a
      cervical spinal cord intramedullary teratoma and treated operatively. The purpose
      of this case report is to describe the highly unusual localization of the
      intramedullary teratoma associated with other vertebral malformations. A review
      of the literature is also presented.

PMID- 16099093
TI  - Phosphorylation of AMPA receptor subunits is differentially regulated by
      phospholipase A2 inhibitors.
AB  - Our laboratory recently discovered that the phosphorylation of subunits forming
      the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) subtype of
      glutamate receptors is regulated by constitutive phospholipase A2 (PLA2) activity
      in rat brain sections. In the present investigation, arachidonyl trifluoromethyl
      ketone (AACOCF3) and bromoenol lactone (BEL) were used to compare the influence
      of calcium-dependent (cPLA2) and calcium-independent (iPLA2) enzymes on
      phosphorylation of AMPA and N-methyl-D-aspartate (NMDA) subtypes of glutamate
      receptors. Incubation of rat brain sections with 3 microM BEL enhanced
      phosphorylation on the serine (Ser) 831 residue of the AMPA receptor GluR1
      subunit in synaptosomal P2 fractions, whereas AACOCF3 at the same concentration
      resulted in increased phosphorylation on residues Ser880/891 of GluR2/3 subunits.
      These effects were restricted to the AMPA receptor subtype as no changes in
      phosphorylation were elicited on the NMDA receptor NR1 subunit. The effects of
      BEL and AACOCF3 were not occluded during blockade of protein phosphatases since
      AMPA receptor phosphorylation was still apparent in the presence of okadaic acid,
      indicating that the PLA2 inhibitor-induced increase in AMPA receptor
      phosphorylation does not rely on a decrease in dephosphorylation reactions.
      However, pretreatment of rat brain sections with a cell-permeable protein kinase
      C (PKC) inhibitor prevented BEL- and AACOCF3-induced phosphorylation on the
      Ser831 and Ser880/891 sites of GluR1 and GluR2/3 subunits, respectively. These
      results suggest that constitutive cPLA2 and iPLA2 systems may differentially
      influence AMPA receptor properties and function in the rat brain through
      mechanisms involving PKC activity.

PMID- 16099094
TI  - Problems with the 'open-hidden' paradigm: the debate is still open and the answer
      is still hidden. Comment on Finniss and Benedetti (Pain 2005;114:3--6).

PMID- 16099096
TI  - Paradoxical burning sensation produced by cold stimulation in patients with
      neuropathic pain.

PMID- 16099095
TI  - A longitudinal study on the predictive validity of the fear-avoidance model in
      low back pain.
AB  - Recently, fear-avoidance models have been quite influential in understanding the
      transition from acute to chronic low back pain (LBP). Not only has pain-related
      fear been found to be associated with disability and increased pain severity, but
      also treatment focused at reducing pain-related fear has shown to successfully
      reduce disability levels. In spite of these developments, there is still a lack
      in well-designed prospective studies examining the role of pain-related fear in
      acute back pain. The aim of the current study was to prospectively test the
      assumption that pain-related fear in acute stages successfully predicts future
      disability. Subjects were primary care acute LBP patients consulting because of a
      new episode of LBP (<or=3 weeks). They completed questionnaires on background
      variables, fear-avoidance model variables and LBP outcome (Graded Chronic Pain
      Scale, GCPS) at baseline, 3, 6, and 12 months follow-up and at the end of the
      study. Two-hundred and twenty-two acute LBP patients were included, of whom 174
      provided full follow-up information (78.4%). A backward ordinal regression
      analysis showed previous LBP history and pain intensity to be the most important
      predictors of end of study GCPS. Of the fear-avoidance model variables, only
      negative affect added to this model. Our results do not really support the
      longitudinal validity of the fear-avoidance model, but they do feed the
      discussion on the role of pain-related fear in early stages of LBP.

PMID- 16099100
TI  - Response to: response to letter regarding 'impaired self-perception of the hand
      in complex regional pain syndrome'.

PMID- 16099099
TI  - Post-traumatic stress disorder symptoms, pain, and perceived life control:
      associations with psychosocial and physical functioning.
AB  - The symptoms of PTSD and pain frequently co-occur following a traumatic event;
      however, very little is known about how these two conditions are associated with
      physical and psychosocial functioning. The current study intended to first
      examine the differential association of co-occurring pain complaints and PTSD
      symptoms with disability in the domains of psychosocial and physical functioning,
      and second, to test whether perceived life control is a mediator of these
      relationships. All participants experienced a motor vehicle accident (MVA) and
      reported pain due to accident-related injuries (n=183). Structural equation
      modeling was used to develop two models hypothesizing a relationship between PTSD
      symptomatology, pain severity, and perceived life control. Separate models were
      constructed for psychosocial and physical functioning, based on the hypothesis
      that pain and PTSD would be differentially related to disability in these two
      domains. Results suggested that more severe PTSD symptoms and greater pain
      complaints were related to psychosocial impairment, however, only pain was
      significantly related to impairment in physical functioning. Perceptions of life
      control were shown to further explain these interrelationships.

PMID- 16099101
TI  - Mechanisms involved in the nociception produced by peripheral protein kinase c
      activation in mice.
AB  - Protein kinase C (PKC) is able to phosphorylate several cellular components that
      serve as key regulatory components in signal transduction pathways of nociceptor
      excitation and sensitisation. Therefore, the present study attempted to assess
      some of the mechanisms involved in the overt nociception elicited by peripheral
      administration of the PKC activator, phorbol 12-myristate 13-acetate (PMA), in
      mice. The intraplantar (i.pl.) injection of PMA (16-1600 pmol/paw), but not its
      inactive analogue alpha-PMA, produced a long-lasting overt nociception (up to 45
      min), as well as the activation of PKCalpha and PKCepsilon isoforms in treated
      paws. Indeed, the local administration of the PKC inhibitor GF109203X completely
      blocked PMA-induced nociception. The blockade of NK1, CGRP, NMDA, beta1
      adrenergic, B2 or TRPV1 receptors with selective antagonists partially decreased
      PMA-induced nociception. Similarly, COX-1, COX-2, MEK or p38 MAP kinase
      inhibitors reduced the nociceptive effect produced by PMA. Notably, the
      nociceptive effect promoted by PMA was diminished in animals treated with an
      antagonist of IL-1beta receptor or with antibodies against TNFalpha, NGF or BDNF,
      but not against GDNF. Finally, mast cells as well as capsaicin-sensitive and
      sympathetic fibres, but not neutrophil influx, mediated the nociceptive effect
      produced by PMA. Collectively, the results of the present study have shown that
      PMA injection into the mouse paw results in PKC activation as well as a
      relatively delayed, but long-lasting, overt nociceptive behaviour in mice.
      Moreover, these results demonstrate that PKC activation exerts a critical role in
      modulating the excitability of sensory neurons.

PMID- 16099103
TI  - Thermal characteristics of Metarhizium anisopliae isolates important for the
      development of biological pesticides for the control of cattle ticks.
AB  - Experiments were conducted to determine if Metarhizium anisopliae isolates which
      are capable of growth at cattle surface temperatures could produce pathogenicity
      to Boophilus microplus in laboratory and field studies. The diurnal temperature
      fluctuation on the surface of cattle was monitored. The temperature tolerance of
      M. anisopliae isolates (ARSEF3297 and IMI386697) was determined and their
      pathogenicity to B. microplus compared at a standard bioassay temperature (28
      degrees C) and at a temperature similar to the cattle surface (31-35 degrees C).
      The effect of the two isolates on the B. microplus population on cattle under
      field conditions was determined. The temperature of the fore udder, rear udder,
      ribs and neck regions of the mixed Holstein cattle fluctuated between 30 and 35
      degrees C, in a similar pattern to the prevailing environmental temperature.
      However, wider fluctuations were obtained on the ears (28-35 degrees C) and spine
      (30-41 degrees C). The colony radius of both isolates declined as temperature
      increased, however, the growth of IMI386697 was five times greater than ARSEF3297
      at 34 degrees C. At 28 degrees C, the pathogenicity of both isolates to B.
      microplus was similar, however, at 31-35 degrees C, IMI386697 was more pathogenic
      than ARSEF3297. Both isolates reduced the B. microplus population on cattle in
      comparison to the control formulation. However, IMI386697 (8.5+/-0.64
      ticks/animal) produced a greater reduction in tick numbers than ARSEF3297 (19.1+/
      0.64 ticks/animal). M. anisopliae was re-isolated from 8.9% of the ticks
      collected from IMI386697 treated cattle as compared to 2.8% of ticks from
      ARSEF3297 treated cattle.

PMID- 16099104
TI  - Tick, fly, and mosquito control--lessons from the past, solutions for the future.
AB  - In order to continue to produce livestock in a sustainable fashion, it is
      suggested that what was used in the past will continue to form the mainstay of
      future control. For the foreseeable future, we must conserve what we have, and
      use it in combination with all the principles of integrated pest management,
      namely strategic and focussed treatments of animals, environmental control of
      breeding sites, disease management (including the principles of enzootic
      stability), and resistant breeds. Whilst new technologies, such as the
      development of vaccines both against the insect pest in some cases or the disease
      they transmit in others, and genetic engineering hold out some hope for the
      future; these are not sufficiently well advanced to permit wholesale application.

PMID- 16099105
TI  - Evaluation of efficacy of heartworm preventive products at the FDA.
AB  - The Center for Veterinary Medicine, U.S. Food and Drug Administration (FDA/CVM)
      has authority under the United States Code 21 under Section 514.80 to monitor for
      adverse experiences of approved animal products. Although veterinarians
      voluntarily report suspect drug-related events to manufacturers, firms that
      market FDA-approved animal products must report serious events to the FDA within
      15 working days of the veterinarian or pet-owner's call to them. Under the
      present regulations, canine heartworm preventatives are approved for 100%
      efficacy after testing in laboratory and field conditions. The report of lack of
      efficacy against heartworm larvae is a serious adverse drug event because the
      resulting condition or the treatment of the condition is life threatening.
      Information on lack of effect that are deemed possibly, probably, or definitely
      drug-related available for review under generic product on the FDA/CVM website
      Surveillance of these reports indicates there are some failures for virtually all
      heartworm prevention product categories. Most failures have been reported in
      heartworm-endemic states. At this time, it is unclear whether these are
      representative of the rare occurrences of failure that have been in existence for
      a long time, but not reported regularly or promptly, or whether there is a true
      increase in complaints of ineffectiveness and real variability between products.
      This paper discusses methods, personnel, and procedures in place in the Division
      of Surveillance that will aid the FDA to better assess heartworm preventive
      treatment failures. It discusses scoring paradigms presently utilized by FDA/CVM
      to assess severity of complaints of lack of efficacy against heartworms, and
      welcomes audience input as to how to improve existing processes. Results suggest
      that more comprehensive reporting will provide FDA/CVM more accurate surveillance
      information regarding efficacy problems. Such practices will permit FDA/CVM to
      better interpret both incidence and severity of in-effect and possible patterns
      of emerging resistance and to convey this in any necessary updated labeling. It
      also indicates that as part of that process, practitioners should return to a
      more conservative testing schedule.

PMID- 16099106
TI  - Aggrecanase-1 (ADAMTS-4) interacts with alpha1-antitrypsin.
AB  - In degradative articular diseases such as rheumatoid arthritis and
      osteoarthritis, loss of the extracellular matrix occurs, resulting in the
      destruction of joint cartilage. Proteolysis of aggrecan is one of the early
      events that leads to breakdown of the extracellular matrix. Aggrecanase-1 (ADAMTS
      -4) is considered to play a pivotal role in the abrasion of cartilage aggrecan in
      rheumatoid arthritis and osteoarthritis. To identify an endogenous inhibitor of
      aggrecanase-1, we performed a yeast two-hybrid screen using the catalytic domain
      of human aggrecanase-1 as a bait and transformed an EGY 48 yeast strain carrying
      the bait plasmid with a human liver cDNA library plasmid. This screen identified
      alpha1-antitrypsin, a member of the family of plasma serine proteinase
      inhibitors, as a prey. Recombinant aggrecanase-1 and alpha1-antitrypsin were
      expressed in mammalian cells and used in co-immunoprecipitation experiments,
      which showed that full-length aggrecanase-1 and alpha1-antitrypsin are also
      associated in vivo. However, aggrecanase-1 did not interfere with the inhibitory
      activity of alpha1-antitrypsin against elastase, and alpha1-antitrypsin had no
      effect on the proteolytic activity of aggrecanase-1. Taken together, these data
      suggest that aggrecanase-1 and alpha1-antitrypsin bind in vivo, although the
      physiological significance of the interaction between aggrecanase-1 and alpha1
      antitrypsin remains unclear.

PMID- 16099107
TI  - Selective inhibitors of terminal deoxyribonucleotidyltransferase (TdT): baicalin
      and genistin.
AB  - Studies of mammalian terminal deoxyribonucleotidyltransferase (TdT) are
      facilitated by use of inhibitors that selectively knock down the activity of the
      enzyme. We have screened for selective inhibitors of TdT and identified a natural
      compound with this property in the Japanese vegetable, Arctium lappa. The
      compound has little effect on the activities of mammalian DNA polymerases, such
      as alpha, beta, delta or lambda polymerase, and prokaryotic DNA polymerases, such
      as Taq DNA polymerase, T4 DNA polymerase and Klenow fragment. H1- and C13-NMR
      spectroscopic analyses showed the compound to be baicalin, a compound previously
      reported as an anti-inflammatory or antipyretic agent. The IC50 value of baicalin
      to TdT was 18.6 microM. We also found that genistin, a baicalin derivative known
      to be antimutagenic, more selectively inhibited TdT activity than baicalin,
      although its IC50 value was weaker (28.7 microM). Genistin and baicalin also
      inhibited the activity of truncated TdT (the so-called pol beta core domain) in
      which the BRCT motif was deleted in its N-terminal region. In kinetic analyses,
      inhibition by either genistin or baicalin was competitive with the primer and non
      competitive with the dNTP substrate. The compounds may, therefore, bind directly
      to the primer-binding site of TdT and simultaneously disturb dNTP substrate
      incorporation into the primer. Genistin and baicalin should prove to be useful
      agents for studying TdT.

PMID- 16099108
TI  - Characterization of the structure of antithrombin-binding heparan sulfate
      generated by heparan sulfate 3-O-sulfotransferase 5.
AB  - The 3-O-sulfation of glucosamine is a key modification step during the
      biosynthesis of anticoagulant heparan sulfate (HS). Both heparan sulfate 3-O
      sulfotransferase -1 (3-OST-1) and 3-O-sulfotransferase-5 (3-OST-5) transfer
      sulfate to the 3-OH group of glucosamine to generate antithrombin-binding heparan
      sulfate (HS(act)). Here, we reported the isolation and characterization of the
      antithrombin-binding HS oligosaccharides generated by 3-OST-5 (3-OST-5
      oligo(act)). (3)H-labeled HS of Chinese hamster ovary cells was exhaustively
      modified by 3-OST-1 to remove the 3-OST-1 modification sites followed by
      antithrombin-affinity fractionation. The non-antithrombin-binding fraction of 3
      OST-1 pretreated HS was further modified by 3-OST-5 to generate additional
      antithrombin-binding HS, which was designated as 3-OST-5 HS(act). Structural
      analysis of 3-OST-5 HS(act) revealed that the antithrombin-binding site of 3-OST
      5 HS(act) is located within a domain clustered with N-sulfated glucosamine units.
      We also isolated 3-OST-5 antithrombin-binding oligosaccharides (3-OST-5
      oligo(act)) from high pH nitrous acid degraded 3-OST-5 HS(act). A disaccharide
      analysis revealed that 3-OST-5 oligo(act) were composed of multiple 3-O-sulfated
      glucosamine units. Our results provide additional insights on the relationship
      between the anticoagulant activity and structure of HS.

PMID- 16099109
TI  - Detection and molecular characterisation of disseminated tumour cells:
      implications for anti-cancer therapy.
AB  - Haematogenous distant metastasis is the leading cause of cancer-related death in
      solid tumours. By applying sensitive immunocytochemical and molecular assays,
      disseminated tumour cells (DTC) in bone marrow (BM) can be detected in 20-40% of
      cancer patients without any clinical or even histopathological signs of
      metastasis, and the presence of these DTC at primary diagnosis predicts the
      subsequent occurrence of overt metastases in bone and other organs. The detection
      and characterisation of DTC in BM may lead to a better understanding of the
      biology initiating metastatic spread in cancer patients and will eventually
      contribute to the development of more effective strategies to eliminate DTC. In
      this review, we will therefore discuss the detection and characterisation of DTC
      in the light of new therapeutic strategies targeting tumour-associated molecules
      and signalling pathways.

PMID- 16099110
TI  - The role of pH dynamics and the Na+/H+ antiporter in the etiopathogenesis and
      treatment of cancer. Two faces of the same coin--one single nature.
AB  - Looked at from the genetic point-of-view cancer represents a daunting and,
      frankly, confusing multiplicity of diseases (at least 100) that require an
      equally large variety of therapeutic strategies and substances designed to treat
      the particular tumor. However, when analyzed phenotypically cancer is a
      relatively uniform disease of very conserved 'hallmark' behaviors across the
      entire spectrum of tissue and genetic differences [D. Hanahan, R.A. Weinberg,
      Hallmarks of cancer, Cell 100 (2000) 57-70]. This suggests that cancers do,
      indeed, share common biochemical and physiological characteristics that are
      independent of the varied genetic backgrounds, and that there may be a common
      mechanism underlying both the neoplastic transformation/progression side and the
      antineoplastic/therapy side of oncology. The challenge of modern oncology is to
      integrate all the diverse experimental data to create a
      physiological/metabolic/energetic paradigm that can unite our thinking in order
      to understand how both neoplastic progression and therapies function. This
      reductionist view gives the hope that, as in chemistry and physics, it will
      possible to identify common underlying driving forces that define a tumor and
      will permit, for the first time, the actual calculated manipulation of their
      state. That is, a rational therapeutic design. In the present review, we present
      evidence, obtained from a great number of studies, for a fundamental, underlying
      mechanism involved in the initiation and evolution of the neoplastic process.
      There is an ever growing body of evidence that all the important neoplastic
      phenotypes are driven by an alkalization of the transformed cell, a process which
      seems specific for transformed cells since the same alkalinization has no effect
      in cells that have not been transformed. Seen in that light, different fields of
      cancer research, from etiopathogenesis, cancer cell metabolism and
      neovascularization, to multiple drug resistance (MDR), selective apoptosis,
      modern cancer chemotherapy and the spontaneous regression of cancer (SRC) all
      appear to have in common a pivotal characteristic, the aberrant regulation of
      hydrogen ion dynamics [S. Harguindey, J.L. Pedraz, R. Garcia Canero, J. Perez de
      Diego, E.J. Cragoe Jr., Hydrogen ion-dependent oncogenesis and parallel new
      avenues to cancer prevention and treatment using a H+-mediated unifying approach:
      pH-related and pH-unrelated mechanisms, Crit. Rev. Oncog. 6 (1) (1995) 1-33].
      Cancer cells have an acid-base disturbance that is completely different than
      observed in normal tissues and that increases in correspondence with increasing
      neoplastic state: an interstitial acid microenvironment linked to an
      intracellular alkalosis.

PMID- 16099111
TI  - [HBs antigen mutants: prevalence, clinical and diagnostic implications].
AB  - The serological diagnosis hepatitis B (HBV) infections relies mainly on the
      detection of the small surface antigen (HBsAg). Immuno-enzymatic assays use
      antibodies directed against epitopes of the major hydrophilic region, in
      particular against a determinant. Genetic variants have been detected in
      vaccinated children, liver transplanted patients receiving anti-HBs
      immunoprophylaxis and chronic carriers with an occult infection (negative HBsAg).
      Substitutions in this region can induce conformational changes abolishing some
      diagnostic antibodies binding leading to false negative results. To estimate the
      prevalence of such substitutions, we studied 55 sequences of the gene S obtained
      between 2002 and 2004, carried out mainly in the search of changes of resistance
      to the lamivudine. The polymorphism of the major hydrophilic region (positions
      102 to 169) was studied using Mutation Master software. Each sequence was
      compared with a consensus sequence of the same genotype. Genotype distribution is
      as follows: D, 40%; With, 20%; C, 16%; B, 11%; E, 9%; F, 2% and G, 2%. Changes
      I195 M and W196L, reflecting lamivudine resistance are present among 18 patients
      (33%). Substitutions of the major absorbent area are found among 31 patients
      (56%), of which a third associated with resistance mutations. The most frequent
      substitutions involved the following amino-acids: F/Y134 (7/31), M133 (6/31),
      D144 (6/31) and G145 (6/31). These two latter are known to be associated anti-HBs
      immunoglobulins or vaccine escape. BLOSUM scores are indicative of substitutions
      inducing important changes of physicochemical properties in 16 patients (29%).
      Such substitutions could thus potentially alter the binding of antibodies used in
      diagnostic assays. In conclusion, changes of the major hydrophilic loop of HBs
      antigen are not rare and could have an important implications for transfusion
      safety and diagnostic reliability.

PMID- 16099112
TI  - Detection of novel oral species and phylotypes in symptomatic endodontic
      infections including abscesses.
AB  - This study was undertaken to investigate the occurrence of several uncultivated
      phylotypes and newly named bacterial species in symptomatic endodontic
      infections. Samples taken from cases clinically diagnosed as acute periradicular
      abscesses or acute periradicular periodontitis were surveyed for the presence of
      12 taxa by means of a 16S rRNA-gene-based nested or hemi-nested PCR assay. The
      most prevalent of the target taxa were Dialister invisus, Olsenella uli,
      Granulicatella adiacens, and Synergistes clones BA121 and E3_33. Findings
      revealed that novel phylotypes and newly named species can take part in the
      microbiota associated with symptomatic endodontic infections and a pathogenetic
      role is suspected.

PMID- 16099113
TI  - Peptidoglycan precursor pools associated with MraY and FtsW deficiencies or
      antibiotic treatments.
AB  - Blocking peptidoglycan synthesis in Escherichia coli with moenomycin or
      vancomycin led to the accumulation of UDP-MurNAc-pentapeptide and of its
      immediate upstream precursors, whereas with cephaloridine or penicillin G the
      pool of UDP-MurNAc-pentapeptide decreased. With MraY and FtsW deficiencies the
      decrease of UDP-MurNAc-pentapeptide was accompanied by an increase of the
      upstream nucleotide precursors and the appearance of UDP-MurNAc-tetrapeptide.

PMID- 16099114
TI  - Smoking habit and genetic factors associated with lung cancer in a population
      highly exposed to arsenic.
AB  - In order to find some relationship between genetic differences in metabolic
      activation and detoxification of environmental carcinogens and host
      susceptibility to chemically induced cancers, we have investigated the
      distribution of the GSTM1 null genotype and CYP450 *1A1 MspI polymorphism in lung
      cancer patients and healthy volunteers of the second region in the north of Chile
      highly exposed to arsenic. The main sources of environmental arsenic exposure in
      Chile are copper smelting and drinking water, specially in the second region, the
      most important copper mining region in the world that shows the highest lung
      cancer mortality rate in the country (35/100.00). The population of Antofagasta,
      the main city of the region was exposed between 1958 and 1970 to arsenic
      concentrations in drinking water of 860 microg/m3, presently declining to 40
      microg/m3. For men the MspI CYP1A1 *2A genotype was associated with a highly
      significant estimated relative lung cancer risk (O.R. = 2.60), but not GSTM1 by
      itself. The relative lung cancer risk for the combined 2A/null GSTM1 genotypes
      was 2.51, which increased with the smoking habits (O.R. = 2.98). In the second
      region the cancer mortality rate for As associated cancers, might be related at
      least part to differences in As biotransformation. In this work we demonstrate
      that genetic biomarkers such as CYP1A1 2A and GSTM1 polymorphisms in addition to
      DR70 as screening biomarkers might provide relevant information to identify
      individuals with higher risk for lung cancer, due to arsenic exposure.

PMID- 16099115
TI  - Higher survival rate of vitrified and thawed in vitro produced bovine blastocysts
      following culture in defined medium supplemented with beta-mercaptoethanol.
AB  - The present study was conducted to compare bovine embryo developmental quality,
      after culture in different defined culture media, up to blastocyst stage, and
      subsequently cultured in media supplemented with beta-mercaptoethanol (beta-ME)
      following blastocyst vitrification and thawing. In part one of this study,
      presumptive zygotes were randomly allocated into the following media: (1) CR1,
      (2) KSOM, (3) SOF, and (4) sequential KSOM-SOF. In the second part of the study,
      blastocysts derived from four different culture media were subjected to a solid
      surface vitrification (35% (v/v) ethylene glycol+0.5M Sucrose+5% (w/v)
      Polyvinylpyrrolidone (PVP), and tested for the effect of beta-ME on their post
      vitrification survival. Following thawing, blastocysts were cultured with or
      without beta-ME. Culture medium had no effect on cleavage rates; however, a
      significantly greater number of zygotes cultured in KSOM, KSOM-SOF, or SOF
      developed to the 8-cell stage, compared with those cultured in CR1. A greater
      proportion of the zygotes cultured in SOF or KSOM-SOF reached blastocysts, than
      did those cultured in CR1 or KSOM. The use of sequential KSOM-SOF significantly
      increased total cell numbers of Day 7 expanded-blastocysts when compared to those
      cultured in CR1, KSOM, or SOF. Addition of beta-ME into culture media after
      vitrification and thawing improved blastocyst survival, hatching rates, and total
      cell numbers of blastocysts. In conclusion, supplementation of beta-ME into
      culture medium after vitrification and thawing significantly increased blastocyst
      survival, hatching rates, and their total cell numbers. These results suggest
      that vitrified IVF embryos should be thawed and briefly cultured in beta-ME
      medium prior to embryo transfer.

PMID- 16099116
TI  - Alteration in haematocrit values and plasma protein fractions during the breeding
      cycle of female pigeons, Columba livia.
AB  - Haematocrit measurements and plasma protein electrophoresis were carried out in
      female pigeons (Columba livia) during the breeding cycle. Non-laying birds showed
      higher (p < 0.001) haematocrit values than those involved in courtship and
      mating, nest-building, incubation and feeding and brooding. Significant
      differences in relative percentage of various plasma protein fractions were
      observed as a function of breeding. Haematocrit could be a useful index to the
      non-laying status of pigeons like that in chickens, Gallus domesticus.

PMID- 16099117
TI  - Doxorubicin-PAMAM dendrimer complex attached to liposomes: cytotoxic studies
      against human cancer cell lines.
AB  - Liposomes composed of HePC:EPC:SA 10:10:0.1 (molar ratio) (1) and EPC:SA 10:0.1
      (molar ratio) (2) were prepared and were used for incorporating the doxorubicin
      PAMAM complex (3:1 molar ratio) (3). The doxorubicin-PAMAM complex was attached
      to liposomes and the incorporation efficiency was 91 and 95% for 1 and 2,
      respectively. The incorporation efficiency for doxorubicin into PAMAM was almost
      97% while doxorubicin to PAMAM molar ratio was 3.56+/-0.04. The release rate of
      doxorubicin as doxorubicin-PAMAM complex from liposomes 1 and 2 and from the
      complex 3, was studied using buffers and 50% RPMI cell culture medium at 37 and
      25 degrees C. The low release rate of doxorubicin as well as the high
      incorporation efficiency of doxorubicin-PAMAM complex into liposomes are
      considered as beneficial factors concerning the activity of doxorubicin. The
      cytotoxic activity of the liposomal formulation 1 incorporating doxorubicin-PAMAM
      complex, based on doxorubicin activity, was compared to that of 2 incorporating
      doxorubicin-PAMAM complex and to that of 3. The results showed that complex 1 was
      the most active formulation against all cancer cell lines compared to that of 2
      and 3. Liposomal formulations composed of lipids and of a drug-dendrimer complex
      could be characterized as modulatory liposomal controlled release system (MLCRS),
      and could provide benefits to the delivery of drugs and modulate their release.

PMID- 16099118
TI  - Evaluation of cyclodextrin solubilization of drugs.
AB  - The most common stoichiometry of drug/cyclodextrin complexes is 1:1, i.e. one
      drug molecule forms a complex with one cyclodextrin molecule, and the most common
      method for stoichiometric determination during formulation studies is the phase
      solubility method. However, in recent years it has becoming increasingly clear
      that solubilizing effects of cyclodextrins are frequently due to the formation of
      multiple inclusion and non-inclusion complexes. The aqueous solubility of 38
      different drugs was determined in pure aqueous solution, aqueous buffer solutions
      and aqueous cyclodextrin solutions, and the apparent stability constant (K1:1) of
      the 1:1 drug/cyclodextrin complexes calculated by the phase-solubility method.
      For poorly soluble drugs (aqueous solubility <0.1mM) the intrinsic solubility
      (S0) is in general much larger than the intercept of the phase-solubility diagram
      (Sint) resulting in non-linearity of otherwise linear (AL-type) phase-solubility
      diagram. This can lead to erroneous K(1:1)-values. A more accurate method for
      determination of the solubilizing efficiency of cyclodextrins is to determine
      their complexation efficiency (CE), i.e. the concentration ratio between
      cyclodextrin in a complex and free cyclodextrin. CE is calculated from the slope
      of the phase-solubility diagrams, it is independent of both S0 and Sint, and more
      reliable when the influences of different pharmaceutical excipients on the
      solubilization are being investigated.

PMID- 16099119
TI  - Development and characterization of sub-micron poly(D,L-lactide-co-glycolide)
      particles loaded with magnetite/maghemite nanoparticles.
AB  - PURPOSE: The objective of this study is to develop biodegradable sub-micron
      poly(lactide-co-glycolide) particles loaded with magnetite/maghemite
      nanoparticles for intravenous drug targeting. METHOD: Sub-micron magnetite/PLGA
      particles (also called composite nanoparticles) were prepared by a modified
      double emulsion method (w/o/w) or by an emulsion-evaporation process (o/w). To
      optimize the composite nanoparticles formulation, the influence of some
      experimental parameters, such as types of magnetite/maghemite nanoparticles,
      volume of magnetite suspension and amount of polymer were investigated. The
      morphology, size and zeta potential of the magnetite/PLGA nanoparticles were
      determined. The magnetite entrapment efficiency and magnetite content were
      assessed by dosing iron in the composite nanoparticles. RESULTS: TEM
      photomicrographs showed that the composite nanoparticles were almost spherical in
      shape with a rather monomodal distribution in size. All composite nanoparticle
      formulations were found to have the mean diameter within the range of 268-327 nm
      with polydispersity index within the range of 0.02-0.15. Magnetite nanoparticles
      coated with oleic acid showed more efficient entrapment (60%) as compared to
      uncoated magnetite nanoparticles (48%). In both cases, when the volume of
      magnetite suspension increased, the magnetite entrapment efficiency decreased but
      the magnetite content increased. In addition, the two-fold rise in the amount of
      polymer did not significantly affect the composite nanoparticle characteristics
      except the magnetite content. Finally, none modification of the mean diameter of
      the composite nanoparticles was observed after storage for 3 months at 4 degrees
      C. CONCLUSIONS: Magnetite/PLGA nanoparticles were prepared and the influence of
      some process parameters have been assessed. Improvement of the magnetite
      entrapment efficiency are in progress and the magnetization properties of the
      composite nanoparticles will subsequently be tested.

PMID- 16099120
TI  - Metabolites and the pharmacokinetics of kobophenol A from Caragana sinica in
      rats.
AB  - This research aims to study the metabolism and pharmacokinetics of phytoestrogen
      kobophenol A (1), the main active compound of Caragana sinica (Buc'hoz) Rehd.
      (Fabaceae), in rats. Metabolites of 1 in rats' feces were isolated and purified
      by multi-chromatograph techniques; three new metabolites of 1, named koboquinone
      A (M1), koboquinone B (M2) and koboquinone C (M3), were isolated, purified from
      rats' feces after they being orally administered with 1. Structure identification
      of the metabolites was fulfilled by spectroscopic analysis. M1 and M2 are
      structurally different to those natural occurring stilbene tetramers, which also
      have para-quinone structure. M1 also showed the activity of stimulating the
      proliferation of cultured osteoblasts. The pharmacokinetics of 1 in rats could be
      described by a two-compartmental model (P<0.05). The half-life was 0.68 h for
      i.v. administration and 5.78 h for oral administration. The oral bioavailability
      of 1 was calculated to be 2.0%; rats tissue distribution experiments show that 1
      was prominently concentrated in livers. Both of the low oral bioavailability and
      the rapid reduction of 1 in blood indicated a suitable formulation is needed
      while it is developed as a new drug.

PMID- 16099121
TI  - The limitation of acute necrosis in retro-patellar cartilage after a severe blunt
      impact to the in vivo rabbit patello-femoral joint.
AB  - We have previously shown that surface lesions and acute necrosis of chondrocytes
      are produced by severe levels of blunt mechanical load, generating contact
      pressures greater than 25 MPa, on chondral and osteochondral explants. We have
      also found surface lesions and chronic degradation of retro-patellar cartilage
      within 3 years following a 6J impact intensity with an associated average
      pressure of 25 MPa in the rabbit patello-femoral joint. We now hypothesized that
      cellular necrosis is produced acutely in the retro-patellar cartilage in this
      model as a result of a 6J impact and that an early injection of the non-ionic
      surfactant, poloxamer 188 (P188), would significantly reduce the percentage of
      necrotic cells in the traumatized cartilage. Eighteen rabbits were equally
      divided into a 'time zero' group and two other groups carried out for 4 days. One
      '4 day' group was administered a 1.5 ml injection of P188 into the impacted joint
      immediately after trauma, while the other was injected with a placebo solution.
      Impact trauma produced surface lesions on retro-patellar cartilage in all groups.
      Approximately 15% of retro-patellar chondrocytes suffered acute necrosis in the
      'time zero' and '4-day no poloxamer' groups. In contrast, significantly fewer
      cells (7%) suffered necrosis in the poloxamer group, most markedly in the
      superficial cartilage layer. The use of P188 surfactant early after severe trauma
      to articular cartilage may allow sufficient time for damaged cells to heal, which
      may in turn mitigate the potential for post-traumatic osteoarthritis. Additional
      studies are needed to improve the efficacy of this surfactant and to determine
      the long-term health of joint cartilage after P188 intervention.

PMID- 16099122
TI  - [Iatrogenic retroperitoneal haematoma after emergency femoral vein
      catheterisation].
AB  - We report a iatrogenic case of retroperitoneal haematoma consecutive to an
      emergency femoral venous catheterization. The indication of the catheterisation
      was a hemorrhagic shock after a dilapidating traumatism of leg in an obese
      patient in whom peripheric venous access was impossible and vascular filling
      urgent. In spite of the existence of an initial reassuring blood backward flow, a
      retroperitoneal haematoma had been constituted gradually and explained an absence
      of haemodynamic improvement in spite of the surgical haemostasis and an adapted
      intravascular filling. The CT scan showed an iatrogenic lesion of the right iliac
      vein and justified the immediate infusion stop. The femoral catheter was
      withdrawn at the 48th hour and the patient discharged at the 6th day.

PMID- 16099123
TI  - [Heat stroke and fulminans hepatitis: is MARS system relevant?].
AB  - Exertional heat stroke (EHS) is a life-threatening condition caused by an extreme
      elevation in core body temperature. Acute liver failure has been reported during
      EHS justifying liver transplantation in some cases. The Molecular Adsorbent
      Recirculating System (MARS) could be indicated in such situations. We report a
      case of a 58-year old patient who suffered acute liver failure occurring after
      EHS. The patient was referred for liver transplantation and benefited of MARS
      therapy. After three sessions of MARS, liver function improved progressively and
      the transplantation was not necessary. The patient completely recovered.

PMID- 16099124
TI  - [Preoperative management of chronic medications].
AB  - This review focuses on potential drug interactions between anaesthetic drugs or
      techniques and chronic medications in patients scheduled for surgery. The vast
      majority of therapeutics can be continued until the morning of surgery. However,
      for some drugs such as ACE inhibitors, there is strong evidence to recommend
      their discontinuation prior to surgery. When juged necessary, interruption of
      chronic therapeutic needs to be anticipated and planned. In the other hand, for
      other drugs such as beta-blockers or L-Dopa, acute withdrawal is associated with
      documented adverse outcome. As a result, such drugs have to be continuing
      throughout the operative period. Although a general consensus exists for many
      medications, there are still controverses as to the management of antithrombotic
      drugs and some central nervous system agents. Advances in anaesthesia include
      knowledge on the mechanisms involved in drug interactions, which allows us to
      improve the preoperative management of chronic therapeutics.

PMID- 16099125
TI  - [Allergic reaction to patent blue dye with positive detection of basophil
      activation by flow cytometry].

PMID- 16099126
TI  - [Predictive value of pericatheter skin cultures in detecting catheter-related
      infections in a medical-surgical intensive care unit].
AB  - OBJECTIVE: To evaluate the predictive value of pericatheter skin cultures in
      detecting catheter-related infections in critically-ill patients. STUDY DESIGN:
      Prospective study. PATIENTS AND METHODS: Over a 5 months period (from August
      1(st) 2001 to December 31 2001), 500 patients were hospitalised, and 108 central
      venous catheters were prospectively examined. For each catheter, blood cultures,
      pericatheter skin cultures and semiquantitative culture of the catheter tip were
      performed. RESULTS: The median duration of catheterization was 8 days
      (interquartile: 8 days). Catheter was removed because of suspected infection in
      54 cases (50%). Systemic catheter-related infection was found in 12 cases (11%)
      and the responsible organism was a gram-negative rod in 11 cases (92%). The
      negative predictive values of pericatheter skin cultures in the diagnosis of
      catheter-related infections and in case of suspected catheter-related infection
      were 89 and 86%, respectively. CONCLUSION: These results indicate that the
      pericatheter skin cultures are not an effective procedure for the conservative
      diagnosis of catheter-related infections and that the skin-insertion wound is not
      the major source of catheter-contamination in our unit.

PMID- 16099127
TI  - [Patient at risk of endocoronary stent thrombosis during perioperative period: a
      frequent situation].

PMID- 16099129
TI  - [Perception and communication of medical risk which implications for preoperative
      anaesthetic consultations?].
AB  - Informing patients about available treatments, their advantages and
      disadvantages, as well as the associated risks, is critical to obtain an informed
      consent and is the responsibility of physicians, including anaesthesiologists.
      However, risks issues are not systematically discussed during anaesthesia
      consultations or are addressed in a vague and incomplete way. In order to improve
      communication and the quality of the informed consent, it is therefore essential
      to scrutinize problems linked to communication about risks. This article is based
      on a review of French and English literature on perception and communication
      about medical risks. Its objectives are for the one hand to summarize the main
      difficulties concerning risk communication in medicine and, on the other hand, to
      offer tools that can foster quality communication with patients especially during
      anaesthesia consultations.

PMID- 16099128
TI  - [Premixed 50% nitrous oxide and oxygen: theoretical recalls and practical
      modalities].
AB  - The concept of premixed 50% nitrous oxide and oxygen dated back to 1961 in
      England, where it is commercialised under the name Entonox. In France, after a so
      marginal use, premixed 50% nitrous oxide and oxygen now knows such a revival
      since we first consider the pain provoked by the cure. To use correctly premixed
      50% nitrous oxide and oxygen, we need to know the main properties of the nitrous
      oxide. The four commercial versions, now on the market, are presented (Kalinox,
      Medimix, Antasol, Oxynox. Except a few contraindications, these indications are
      large, as well at hospital as outside. In less than 10% of the cases, side
      effects are possible. Conditions of administration are given in details. The
      limits of the technic and the particular precautions of use are precised.

PMID- 16099131
TI  - [Evaluation of the information given to parents during the planned preanaesthetic
      consultation in a paediatric hospital].
AB  - INTRODUCTION: Information given to the parents of paediatric patients during the
      preanaesthetic consultation (CS) must be understandable. OBJECTIVE: We have
      studied the impact of this information given during CS. METHODS: Prospective
      study over four months with a questionnaire completed by parents after CS and
      before the hospitalization. The Sfar information booklet was given to the parents
      before CS. The study evaluated whether the information had been given ("have you
      received the information on...?"), understood ("Did you understand...?"), and if
      CS had influenced anxiety of parents/child; on four items of information,
      anesthetic risk, transfusion, postoperative pain, and anesthetic technique. The
      questionnaire noted also the parents sociocultural level (NSC), and if they had
      read the Sfar booklet. Statistical analysis (descriptive, uni-, multivariate),
      p<0.05. RESULTS: Four hundred questionnaires were distributed, 334 were analyzed.
      The information on the four items was considered to have been given in 75%,
      understood 72%, and to have diminished anxiety 68%. These results were not
      influenced by whether or not (88%) parents had read the Sfar booklet. How much
      information was given was a function of the physician giving the information.
      Elevated NSC and amount if information given improved comprehension optimized.
      Diminution of anxiety was when all four items were understood, CS was performed
      by a senior physician and the parent's NSC was high. DISCUSSION: Information
      better adapted to NSC may improve the quality of CS. The Sfar booklet does not
      contribute to parents understanding in this context.

PMID- 16099130
TI  - [Isolated acquired factor VII deficiency in patient with severe head trauma: use
      of factor VII (factor VII-LFB].
AB  - We report a case of transient acquired and isolated factor VII deficiency
      associated with severe head trauma. A 16-year-old boy was involved in a motor
      vehicle accident. CT scan showed frontal brain contusion and a cerebral haematoma
      (5 cm). First prothrombine time (PT) was normal. Rapidly, a severe coagulopathy
      developed, unresponsiving to fresh frozen plasma and vitamin K. Haemostatic
      markers analysis showed an isolated deficiency of factor VII at 15%. No
      inhibitory activity against factor VII could be detected. We successfully treated
      the deficiency with intermittent intravenous human factor VII (factor VII-LFB)
      during 10 days. Factor VII return to normal at 84%. Physiopathological and
      therapeutic aspects of this rare pathology are presented.

PMID- 16099132
TI  - [Near miss stuck in the throat: when the organization generates undesirable
      event...].

PMID- 16099133
TI  - [Beware of the residual curarization!].

PMID- 16099134
TI  - Haemophilus influenzae luxS mutants form a biofilm and have increased virulence.
AB  - To gain insight into the role of luxSHi in disease pathogenesis, we inactivated
      that gene in several non-typeable Haemophilus influenzae isolates with an
      antibiotic resistance cassette. Gene inactivation was confirmed by PCR and by
      Southern blot analysis in each strain. Culture filtrates from luxSHi mutants
      contained a decreased amount of autoinducer-2 (AI-2) activity in comparison to
      the wild-type isolates using the Vibrio harveyi BB170 bioassay. Culture filtrates
      from Escherichia coli strain DH5alpha expressing a cloned luxSHi contained 350
      fold more AI-2 activity per cell than E. coli DH5alpha containing the vector
      alone. The growth rate in several liquid media, and the cell density after
      overnight growth were not significantly different between the parents and the
      luxSHi mutants. Two clinical H. influenzae and their luxSHi mutants produced an
      identical biofilm in a flow system. Invasion of human cells by the luxSHi
      mutants, in comparison to the wild-type parents was strain-dependent, and cell
      type-dependent, but the luxSHi mutants tended to be more invasive. The luxSHi
      mutant of an otitis media isolate, strain R3157 appeared more virulent in the
      chinchilla model of otitis media: there were more bacteria in the middle ear, a
      greater inflammatory response and more goblet cell hyperplasia 10 days after the
      inoculation. We conclude that the H. influenzae homologue of luxS modulates
      certain virulence traits.

PMID- 16099135
TI  - CXCL8 secretion by dendritic cells predicts contact allergens from irritants.
AB  - Monocyte-derived dendritic cell functions have been explored for identification
      of contact allergens in vitro. Current methods, including measurement of changes
      in cell surface marker expression (e.g. CD83, CD86) do not provide a sensitive
      method for detecting the sensitising potential of a chemical. In this study, we
      investigated whether chemokine production by monocyte-derived dendritic cells is
      increased upon maturation and whether chemokine production can provide
      methodology for the detection of allergens. Monocyte-derived dendritic cells were
      exposed to allergens (nickel sulphate, cobalt chloride, palladium chloride,
      copper sulphate, chrome-(III)-chloride, potassium dichromate, p-phenylenediamine
      and dinitrochlorobenzene) and irritants (sodium dodecyl sulphate,
      dimethylsulphoxide, benzalkoniumchloride and propane-1-ol). CD83 and CD86
      expression was analysed by flow cytometry and chemokine production (CXCL8, CCL5,
      CCL17, CCL18, CCL19, CCL20, CCL22) was determined by ELISA. Significant up
      regulation of CD83 and CD86 expression could only be induced by three out of
      seven and five out of seven allergens, respectively. In contrast, CXCL8
      production was significantly increased after stimulation with all allergens
      tested, whereas irritant exposure led to decreased CXCL8 production. All other
      chemokines tested, failed in identifying contact allergens. In conclusion, CXCL8
      production, next to CD83 and CD86 up regulation, by monocyte-derived dendritic
      cells provides a promising in vitro tool for discrimination between allergens and
      irritants.

PMID- 16099136
TI  - Toxicity of tire debris extracts on human lung cell line A549.
AB  - TD, produced by tire wear, is a significant constituent of PM(10) in urban areas
      where traffic related emissions are predominant. TD contains a lot of chemicals
      which can affect human respiratory system and it has received little attention
      until now, even the toxicity of PM has been extensively documented. A549 cells, a
      human alveolar lung cells, were exposed for 24, 48, 72 h to 10, 50, 60, 75
      microg/ml of TD organic extract. MTT and Trypan Blue assays were used to evaluate
      cytotoxicity and Comet Assay to evidence DNA damage. TD extracts induced a dose
      dependent increase in cell mortality and DNA damage. A significant toxicity was
      observed when cells were exposed to 60 microg/ml for 72 h. Moreover cell
      morphology observed at ultra structural level, was severely affected at the
      highest dose.

PMID- 16099137
TI  - Detecting simulated memory impairment: further validation of the Word Completion
      Memory Test (WCMT).
AB  - The Word Completion Memory Test (WCMT) was developed to detect sophisticated
      attempts at simulating memory impairment. The primary purpose of the present
      study was to provide additional validity and reliability information about the
      WCMT. Seventy-one participants were recruited for this study: 30 normal
      volunteers and 11 memory-disordered patients instructed to perform their best,
      and 30 normal volunteers instructed to fake memory impairment. Normal volunteers
      were administered five tests of neuropsychological functioning and five tests of
      simulation to explore the convergent and divergent validity of the WCMT. Two
      weeks later, these participants completed all 10 measures a second time. Memory
      disordered patients were administered the WCMT and two additional simulation
      measures as part of a comprehensive neuropsychological evaluation. The WCMT
      successfully discriminated simulators from nonsimulators with an overall
      classification accuracy of 97% and demonstrated good psychometric properties. In
      conclusion, the WCMT continues to show promise as a measure of simulated memory
      impairment.

PMID- 16099138
TI  - Rates of isolated sleep paralysis in outpatients with anxiety disorders.
AB  - Initial research suggests that rates of isolated sleep paralysis (ISP) are
      elevated in individuals with panic disorder and particularly low in individuals
      with other anxiety disorders. To further evaluate these findings, we examined
      rates of ISP in a sample outpatients with primary diagnoses of panic disorder
      (n=24), social anxiety disorder (n=18), or generalized anxiety disorder (n=18).
      We obtained an overall rate of ISP of 19.7%; rates for patients with panic
      disorder (20.8%) fell between those with generalized anxiety disorder (15.8%) and
      social phobia (22.2%). Analysis of comorbidities failed to provide evidence of
      link between depressive disorders and ISP, but did indicate a significant
      association between anxiety comorbidity and higher rates of ISP. Results are
      discussed relative to other variables predicting variability in the occurrence of
      ISP.

PMID- 16099139
TI  - In vitro and in vivo effects of deoxynivalenol (DNV) on regulators of cap
      dependent translation control in porcine endometrium.
AB  - Deoxynivalenol (DNV) is the most frequently encountered trichothecene in grain
      based foods, and is able to produce toxic effects resulting in various diseases
      in farm and laboratory animals. The molecular mechanisms that control this
      mycotoxin mediated effects in porcine endometrial cells are far from being
      completely understood. Recent results show that DNV inhibits protein synthesis in
      actively proliferating tissues. Therefore, the present study investigated the
      effects of this mycotoxin on a cellular level in an in vivo and in vitro system.
      The abundance and phosphorylation state (activity) of the cell cycle dependent
      kinases MAPk and Akt (PKB) and their potential targets eIF-4E (eukaryotic
      initiation factor 4E) and 4E-BP1 (4E binding protein, eIF4E repressor protein)
      were examined. In previous investigations it was found that these factors are
      involved in initiation of mRNA translation. The results show that DNV in vitro
      strongly reduce the abundance of p38 MAPk, protein kinase Akt and the alpha- and
      beta-4E-BP1 bands. The phosphorylation state of these proteins was obviously not
      modulated. In contrast, the eIF4E phosphorylation was strongly reduced in DNV
      treated cells. In summary, our in vitro results let assume that DNV potentially
      influences gene expression, but this work does not present a direct proof that
      DNV alters processes, which are involved in the initiation of mRNA translation.
      Surprisingly in vivo, an influence of DNV feeding on the investigated molecular
      events could not be demonstrated.

PMID- 16099140
TI  - Cyto- and chemoarchitecture of the dorsal thalamus of the monotreme Tachyglossus
      aculeatus, the short beaked echidna.
AB  - We have examined the cyto- and chemoarchitecture of the dorsal thalamus of the
      short beaked echidna (Tachyglossus aculeatus), using Nissl and myelin staining,
      immunoreactivity for parvalbumin, calbindin, calretinin and non-phosphorylated
      neurofilament protein (SMI-32 antibody), and histochemistry for
      acetylcholinesterase and NADPH diaphorase. Immunohistochemical methods revealed
      many nuclear boundaries, which were difficult to discern with Nissl staining.
      Parvalbumin immunoreactive somata were concentrated in the ventral posterior,
      reticular, posterior, lateral and medial geniculate nuclei, while parvalbumin
      immunoreactivity of the neuropil was present throughout all but the midline
      nuclei. Large numbers of calbindin immunoreactive somata were also found within
      the midline thalamic nuclei, and thalamic sensory relay nuclei. Immunoreactivity
      for calretinin was found in many small somata within the lateral geniculate "a"
      nucleus, with other labelled somata found in the lateral geniculate "b" nucleus,
      ventral posterior medial and ventral posterior lateral nuclei. Immunoreactivity
      with the SMI-32 antibody was largely confined to somata and neuropil within the
      thalamocortical relay nuclei (ventral posterior medial and lateral nuclei,
      lateral and medial geniculate nuclei and the posterior thalamic nucleus). In
      broad terms there were many similarities between the thalamus of this monotreme
      and that of eutheria (e.g. disposition of somatosensory thalamus, complementarity
      of parvalbumin and calbindin immunoreactive structures), but there were some
      unique features of the thalamus of the echidna. These include the relatively
      small size of the thalamic reticular nucleus and the preponderance of calbindin
      immunoreactive neurons over parvalbumin immunoreactive neurons in the ventral
      posterior nucleus.

PMID- 16099141
TI  - Stochastic resonance in noisy spiking retinal and sensory neuron models.
AB  - Two new theorems show that small amounts of additive white noise can improve the
      bit count or mutual information of several popular models of spiking retinal
      neurons and spiking sensory neurons. The first theorem gives necessary and
      sufficient conditions for this noise benefit or stochastic resonance (SR) effect
      for subthreshold signals in a standard family of Poisson spiking models of
      retinal neurons. The result holds for all types of finite-variance noise and for
      all types of infinite-variance stable noise: SR occurs if and only if a sum of
      noise means or location parameters falls outside a 'forbidden interval' of
      values. The second theorem gives a similar forbidden-interval sufficient
      condition for the SR effect for several types of spiking sensory neurons that
      include the Fitzhugh-Nagumo neuron, the leaky integrate-and-fire neuron, and the
      reduced Type I neuron model if the additive noise is Gaussian white noise.
      Simulations show that neither the forbidden-interval condition nor Gaussianity is
      necessary for the SR effect.

PMID- 16099142
TI  - Death or survival: membrane ceramide controls the fate and activation of antigen
      specific T-cells depending on signal strength and duration.
AB  - Sphingomyelinase (SMase)-mediated release of ceramide in the plasma membrane of T
      lymphocytes induced by different stimuli such as ligation of Fas/CD95,
      irradiation, stress, inflammation or anticancer drugs primarily involves
      mitochondrial apoptosis signaling, but under specific conditions non-apoptotic
      Fas-signaling was also reported. Here we investigated, using a quantitative
      simulation model with exogenous C2-ceramide (and SMase), the dependence of
      activation and fate of T-cells on the strength and duration of ceramide
      accumulation. A murine, influenza virus hemagglutinin-specific T-helper cell
      (IP12-7) alone or together with interacting antigen presenting B-cells (APC) was
      used. C2-ceramide induced apoptosis of TH cells above a 'threshold' stimulus (>25
      microM in 'strength' or >30 min in duration), while below the threshold C2
      ceramide was non-apoptotic, as confirmed by early and late apoptotic markers (PS
      translocation, mitochondrial depolarization, caspase-3 activation, DNA
      fragmentation). The modest ceramide stimuli strongly suppressed the calcium
      response and inhibited several downstream signal events (e.g. ERK1/2-, JNK
      phosphorylation, CD69 expression or IL-2 production) in TH cells during both anti
      CD3 induced and APC-triggered activation. Ceramide moderately affected the Ca2+ 
      release from internal stores upon antigen-specific engagement of TCR in
      immunological synapses, while the influx phase was remarkably reduced in both
      amplitude and rate, suggesting that the major target(s) of ceramide-effects are
      membrane-proximal. Ceramide inhibited Kv1.3 potassium channels, store operated
      Ca2+ -entry (SOC) and depolarized the plasma membrane to which contribution of
      spontaneously formed ceramide channels is possible. The impaired function of
      these transporters may be coupled to the quantitative, membrane raft-remodeling
      effect of ceramide and responsible, in a concerted action, for the suppressed
      activation. Our results suggest that non-apoptotic Fas stimuli, received from
      previously activated, FasL+ interacting lymphocytes in the lymph nodes, may
      negatively regulate subsequent antigen-specific T-cell activation and thus
      modulate the antigen-specific T-cell response.

PMID- 16099143
TI  - Effects of pulmonary surfactant system on rifampicin release from rifampicin
      loaded PLGA microspheres.
AB  - Pulmonary surfactants little affected the release ratio of rifampicin from
      rifampicin-loaded poly(lactide-co-glycolide) PLGA microspheres. The release ratio
      of rifampicin was depending on pH of pulmonary surfactant solution, showing that
      rifampicin-loaded PLGA microspheres have an ideal property to deliver rifampicin
      into alveolar macrophages inside of which Mycobacterium tuberculosis bacilli
      reside and to kill them. That is, little amount of rifampicin is released in
      alveolar lining liquid before the microspheres are phagocytosed by alveolar
      macrophages, then rifampicin is released in phagosome or cytoplasm, but little
      amount of rifampicin is released in lysosome of alveolar macrophages after the
      microspheres are internalized. Pulmonary surfactants also little affected the
      changes in molecular weight of residual PLGA during its hydrolytic degradation
      process. From the electrophoretic mobility measurements of PLGA microspheres, it
      was shown that pulmonary surfactants changed the surface charge density of PLGA
      microspheres by adsorbing on their surfaces.

PMID- 16099144
TI  - Variability of bacterial translocation in the absence of intestinal mucosal
      damage following injury and the influence of interleukin-6.
AB  - Bacterial translocation and intestinal mucosal damage have been reported as
      potentially clinically important sequelae of injury. Evidence that endogenous
      interleukin-6 (IL-6) is able to protect against infection, and that orally
      administered IL-6 could prevent bacterial translocation and mucosal damage
      following haemorrhage, led us to evaluate the impact of injury on the intestinal
      mucosa and the role of endogenous IL-6. Normal and IL-6-deficient (IL-6-/-) mice
      were subjected to haemorrhage of increasing severity, hind limb ischaemia, or
      both. Mucosal integrity and bacterial translocation to the liver, spleen and
      mesenteric lymph nodes (MLN) were examined after 16 h. Bacterial translocation to
      each of these tissues was observed in unoperated animals. The more severe
      haemorrhage procedures, and hind limb ischaemia, increased bacterial
      translocation to the liver significantly in most experiments with normal mice.
      The IL-6-/- mice survived the most severe haemorrhage procedure less well (p =
      0.0015), although increased bacterial translocation was not seen. There was no
      clear evidence of mucosal damage, or bacterial translocation to spleen and
      mesenteric lymph nodes, in either normal or IL-6-/- mice. Intestinal IgA
      concentrations were the same in IL-6-/- mice and controls. These data demonstrate
      that increased bacterial translocation can be observed following severe injury,
      but that neither bacterial translocation nor severe injury are inevitably
      associated with morphological damage to the intestinal mucosa, and endogenous IL
      6 is more likely to promote bacterial translocation than protect the gut.

PMID- 16099145
TI  - [Lorraine childhood cancer registry: incidence, survival 1983-1999].
AB  - BACKGROUND: Cancer in childhood account for less than 1% of all cancers and for
      the second most important cause of death for children aged less than 15 years in
      France, injuries being the leading cause. Compared to adult cancers, childhood
      cancers' particularities justify to create pediatric registries. The first French
      population-based registry was created in Lorraine in 1983. The incidence and
      survival results from a 17 year-period are presented. METHODS: In Lorraine
      region, all children (0-14 years) with cancer diagnosed between 1983 and 1999
      were included. Crude, age-standardized (world population) and cumulative
      incidence rates were calculated just as overall, specific-disease and event-free
      survival rates, using Kaplan-Meier methods. RESULTS: With 1086 registered cases,
      the crude incidence rate per million children is 132.4, the age-standardized
      incidence rate per million is 137.5; 1 out of every 500 children will develop
      cancer before the age of 15 years. The incidence of all cancers combined is
      slightly higher in males than in females with a M/F ratio of 1.13. For this 17
      years-period, no trend in childhood cancer incidence is observed. The main cancer
      groups are leukemia (30.7%), brain and spinal tumors (23.2%) and lymphomas
      (12.9%), sympathetic nervous system tumors (7.4%), soft-tissue sarcomas (6.1%),
      renal tumors (5.2%), and bone tumors (5.0%). Five-year specific survival rates
      for all cancers combined is 71.4% [95% CI: 68.5-74.3]. The prognosis is
      significatively worse for the<1 year age group (55%) and for some histologic
      types: brain stem gliomas (27%), hepatic tumors (43%), osteosarcomas (57%),
      neuroblastomas (65%), rhabdomyosarcomas (55%). DISCUSSION: Relative distribution
      of histologic groups, incidence and survival rates observed in Lorraine registry
      are compatible with the general pattern in the European Union cancer registries.
      The lack of significative trend in incidence unlike others country may be
      explained by too small numbers. CONCLUSION: The acquired experience in
      developping this regional registry allowed us to create a national registry of
      childhood solid tumors and contribute to valid national data.

PMID- 16099146
TI  - [Intracranial hypertension in an infant treated with fluoroquinolone in
      Madagascar].

PMID- 16099147
TI  - [Acceptability and tolerance of sodium valproate, a new sustained-action granule
      formulation, in monotherapy for epileptic children from 3 years old].
AB  - Sodium valproate (VPA) is an anti-epileptic drug which was until now administered
      to children as drinkable or injectable form. A new galenic form of this compound
      has been developed as microgranules with prolonged release (Micropakine)LP; MPK).
      This new galenic form of VPA allows a greater stability of the plasmatic rates,
      thus limiting the risk of amount-dependent adverse effects at the time of the
      peaks, and of less effectiveness at the time of the fall of the circulating
      rates. The main objective of this study was to evaluate the acceptability of the
      new galenic form of VPA, in monotherapy, for epileptic children with >or=3 years
      old. The evaluation was performed at day (D)90 by the patients using a hedonic
      visual scale. The secondary objectives were to evaluate the acceptability by the
      parents, the treatment compliance, the percentage of patients free of seizure at
      D 90, and the tolerance. Finally, the authors compared all these data to those
      recovered at the baseline in patients already treated by the previous drinkable
      VPA. A total of 307 patients were involved by 76 hospital neuropediatric
      physicians. The population was constituted by 110 children <5 years old and 197
      children from 5 to 14 years old. MPK was well accepted for total population at D
      90 (<5 years old: 83.3%; >or=5 years old: 80%). For patients previously treated
      by drinkable form of VPA (N=199), MPK was significantly better accepted than the
      drinkable form at D1 (<5 years, P=0.0189; >or=5 years, P<0.0001). Less
      difficulties were experienced by the parents to administrate MPK when compared to
      the drinkable form (P<0.001), mainly due to his neutral taste. Patients free of
      seizure at D 90 were 77% [70,3; 82,5]. Specially, fewer epileptic seizures were
      evidenced for all children previously treated at D1 by drinkable form of VPA. The
      treatment was well respected by the patients, which were compliant in 80% of the
      cases. The adherence to treatment was good since the treatment compliance was
      87%. MPK was well tolerated. CONCLUSION: MPK in the microgranule form
      significantly improves the treatment acceptability with a good tolerance. Two
      daily intakes and neutral taste are two major advantages to favour the compliance
      in children, thus contributing to the efficacy of the antiepileptic treatment.

PMID- 16099148
TI  - SiMCAL 1 algorithm for analysis of gene expression data related to the
      phosphatidylserine receptor.
AB  - OBJECTIVE: SiMCAL 1 (simple multilevel clustering and linking, version 1) is a
      novel clustering algorithm for time-series microarray data, presented here with
      an application to a specific data set. The purpose of the algorithm is to present
      a complete feature set not found in either Jarvis-Patrick clustering, from which
      it is derived, or in other popular clustering methods such as hierarchical and k
      means. The data concern the activity of the phosphatidylserine receptor (PSR)
      which is believed to be a crucial molecular switch in the mediation of
      inflammatory response in apoptosis and lysis. By analyzing the behavior of PSR
      related genes in mouse macrophages, we hope to elucidate the mechanisms involved
      in this important biological process. METHODS AND MATERIALS: SiMCAL 1 is
      implemented in the Python programming language using the Numerical Python
      extensions, and the data are stored using the MySQL database management system.
      The data are derived from exposures of multiple Affymetrix mouse gene microarray
      chips to elevated levels of PSR antibody and control conditions. Code and data
      are available at (accessed: 17 January 2005). RESULTS: The algorithm meets its
      objectives: it is simple, in that it is computationally inexpensive; it is
      multilevel, in that it provides a small number of clearly defined hierarchical
      levels of clusters; and it offers linking between clusters at the same level in
      each hierarchy. Clustering and linking results indicate previously unknown co
      regulation for genes expressing PGH synthase (COX2) and PGE2, appear to confirm
      increased production of proteins for clearance of apoptotic cells in the presence
      of PSR antibody, and correspond to other findings regarding the temporal
      relationship between PGE2 production and B cell proliferation and
      differentiation. These results are promising but should be taken as highly
      preliminary. CONCLUSION: Both the algorithm and its application to this problem
      show great potential for future development. We plan to improve and extend the
      SiMCAL family of algorithms, and to obtain new data so that the algorithm(s) may
      be further applied to this and other problems of interest.

PMID- 16099149
TI  - An international observational prospective study to determine the cost of asthma
      exacerbations (COAX).
AB  - Asthma is a common chronic condition that places substantial burden on patients
      and healthcare services. Despite the standards of asthma control that
      international guidelines recommend should be achieved, many patients continue to
      suffer sub-optimal control of symptoms and experience exacerbations (acute asthma
      attacks). In addition to being associated with reduced quality of life, asthma
      exacerbations are a key cost driver in asthma management. Routine clinical
      practice for the management of asthma exacerbations varies in different
      healthcare systems, so healthcare providers require local costs to be able to
      assess the value of therapies that reduce the frequency and severity of
      exacerbations. This prospective study, conducted in a total of 15 countries,
      assessed the local cost of asthma exacerbations managed in either primary or
      secondary care. Healthcare resources used were costed using actual values
      appropriate to each country in local currency and in Euros. Results are presented
      for exacerbations managed in primary care in Brazil, Bulgaria, Croatia, Czech
      Republic, Hungary, Poland, Russia, Slovakia, Slovenia, Spain and Ukraine, and in
      secondary care in Croatia, Denmark, Ireland, Latvia, Norway, Poland, Russia,
      Slovakia, Slovenia and Spain. Multiple regression analysis of the 2052
      exacerbations included in the economic analysis showed that the cost of
      exacerbations was significantly affected by country (P<0.0001). Mean costs were
      significantly higher in secondary care (euro 1349) than primary care (euro 445,
      P=0.0003). Age was a significant variable (P=0.0002), though the effect showed an
      interaction with care type (P<0.0001). As severity of exacerbation increased, so
      did secondary care costs, though primary care costs remained essentially
      constant. In conclusion, the study showed that asthma exacerbations are costly to
      manage, suggesting that therapies able to increase asthma control and reduce the
      frequency or severity of exacerbations may bring economic benefits, as well as
      improved quality of life.

PMID- 16099150
TI  - Frequency of gastroesophageal reflux disease in nonatopic children with asthma
      like airway disease.
AB  - Gastroesophageal reflux disease (GERD) is commonly associated with asthma;
      however, frequency in nonatopic children with asthmatic symptoms is unknown. The
      aim of this study was to determine the frequency of gastroesophageal reflux (GER)
      in nonatopic children with asthma-like airway disease that recur despite
      conventional asthma treatment and to evaluate the clinical response to
      lansoprazole treatment. Twenty-five nonatopic children aged between 1 and 16
      years who have asthma-like airway disease and 25 healthy children were included
      in the study. All cases underwent 24 h pH monitoring with dual sensor catheters.
      Additionally, acid suppressor treatment was administered to patients diagnosed as
      having GERD and clinical response was evaluated. Major symptoms encountered in
      the patient group included wheezing and cough (88%, and 32%, respectively).
      Reflux episodes were more common in distal esophagus during the prone position
      (reflux index (RI) of 11.5+/-10.3 vs. 16.2+/-9.4 during supine vs. prone). All
      distal esophageal parameters were significantly higher in the patient group
      except number of reflux episodes lasting longer than 5 min (RI of 13.3+/-13.1 vs.
      3.9+/-2.9 in the patient vs. control groups, respectively). There was a
      significant improvement in symptoms and requirement for medication with treatment
      (number of systems decreased from 2.3+/-0.6 to 0.4+/-0.6, P=0.00). In conclusion,
      GERD is significantly more common in nonatopic children with asthma-like airway
      disease compared to the controls and clinical improvement is significant after
      acid suppressor treatment. Thus, we suggest that children followed-up with the
      diagnosis of nonatopic asthma with recurrent exacerbations despite adequate
      asthma treatment have a high frequency of GER and that lansoprazole treatment may
      be considered early in management.

PMID- 16099151
TI  - Elevated levels of natriuretic peptides in patients with pulmonary
      thromboembolism.
AB  - BACKGROUND: Pulmonary thromboembolism (PTE) occurs in a wide variety of clinical
      settings and presents a diagnostic challenge to clinicians, often requiring
      extensive imaging of the vascular bed. Management increasingly requires accurate
      risk stratification to rapidly identify those with massive and submassive PTE
      requiring different therapeutic strategies such as thrombolysis. Provision of a
      rapid blood test that improves diagnostic certainty and helps stratify risk could
      therefore bridge the gap between uncertainty and delivery of immediate early life
      saving treatment. METHODS AND RESULTS: One hundred and fourteen consecutive
      patients with suspected PTE underwent prospective evaluation. Venous blood
      samples were obtained from an unselected group referred for ventilation-perfusion
      scintigraphy. B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP)
      and N-terminal pro-ANP (N-ANP) were measured by radioimmunoassay using
      commercially available kits. The scans were classified into three groups
      according to standard criteria (PIOPED); normal scan (N) (n=20), low/intermediate
      probability (L/I) of PTE (n=77) and high probability (H) of PTE (n=17).
      Comparisons were also made between patients with high probability scans who died
      (n=3) and those who survived (n=14). Values are quoted for the median and
      interquartile ranges. There were statistically significant differences between
      groups for levels of (a) BNP (P<0.001): N=6.7 pmol/l (5.6-11.9), L/I=12.5 pmol/l
      (6.7-28.2) and H=18.5 pmol/l (12.6-74.6); (b) ANP (P<0.005): N=12.6 pmol/l (7.1
      16.0), L/I=19.51 pmol/l (12.5-28.2) and H=19.1 pmol/l (15.7-31.7) and (c) N-ANP
      (P<0.05): N=177 pmol/l (119-200), L/I=302 pmol/l (152-576) and H=322 pmol/l (223
      563). Levels of BNP and ANP were significantly (P<0.05) higher in patients with
      high probability scans and a diagnosis of PTE who died (n=3) than in those who
      survived (n=14); BNP: 91.6 pmol/l (77.5-336.2) vs. 14.4 pmol/l (11.9-27.4) and
      ANP 32.5 pmol/l (21.7-105.5) vs. 17.6 pmol/l (15.2-19.3), respectively.
      CONCLUSIONS: PTE is associated with significantly elevated levels of the
      natriuretic peptides ANP, BNP and N-ANP. Increasing ventilation-perfusion
      mismatch on scintigraphy corresponds to incremental increases in the levels of
      ANP, BNP and N-ANP found. These peptides, and in particular BNP, may add to the
      diagnosis by rapidly providing a probability of PE before dedicated imaging
      studies can be performed. Natriuretic peptides require further study to establish
      their role in identifying a high-risk group who may benefit from early treatments
      such as thrombolysis.

PMID- 16099152
TI  - The comings and goings of actin: coupling protrusion and retraction in cell
      motility.
AB  - Cells utilize actin filaments to produce protrusive and contractile arrays that
      cooperate to drive cell motility. The generation of the two arrays and the
      coupling between them result from the unique properties of the lamellipodium, a
      protrusive leaflet of cytoplasm at the cell edge. From the lamellipodium into the
      lamella behind, there is a transition from a fast retrograde flow of actin
      polymer driven by polymerization to a slow flow driven by the interaction of anti
      parallel arrays of actin with myosin. In addition to driving protrusion, the
      lamellipodium appears to play a role in supplying filaments to the lamella for
      the assembly of the contractile network required for traction.

PMID- 16099153
TI  - Two-dimensional micro-bubble actuator array to enhance the efficiency of
      molecular beacon based DNA micro-biosensors.
AB  - Two-dimensional micro-bubble actuator arrays were developed and studied in detail
      to enhance the hybridization kinetics of a DNA micro-biosensor. The hybridization
      between a molecular beacon, a kind of oligonucleotide probe, and its complement
      was investigated in a millimeter-sized PDMS based reaction chamber, where various
      2D micro-heater arrays were distributed on the bottom for micro-bubble
      generation. The hybridization assay without the micro-bubble actuation revealed
      that the fluorescence increased fast at the beginning and slowed down after that.
      However, a uniform fluorescence increase was observed when periodic micro-bubble
      agitation was introduced in the static hybridization solution. A comparison of
      hybridization assays with and without micro-bubble agitation revealed that the
      hybridization time could be effectively shortened by 33% with 10 cycles of micro
      bubble agitation from a 2 x 1 bubble actuator array, and by 43% with 10 cycles of
      micro-bubble agitation from a 2 x 2 bubble actuator array.

PMID- 16099154
TI  - Microfluidic pH-sensing chips integrated with pneumatic fluid-control devices.
AB  - This paper presents a microfluidic chip capable of performing precise continuous
      pH measurements in an automatic mode. The chip is fabricated using micro-electro
      mechanical-systems (MEMS)-based techniques and incorporates polydimethylsiloxane
      (PDMS) microstructures, pH-sensing electrodes and pneumatic fluid-control
      devices. Through its enhanced microchannel design and use of pneumatic fluid
      control devices, the microfluidic chip reduces the dead volume of the sample and
      increases the pumping rate. The maximum pumping rate of the developed micro-pump
      is 28 microL/min at an air pressure of 10 psi and a driving frequency of 10 Hz.
      The total sample volume consumed in each sensing operation is just 0.515 microL.
      As a result, the developed chip reduces the sample volume compared to
      conventional large-scale pH-sensing systems. The microfluidic chip employs the
      electrochemical sensing method to conduct precise pH level measurements. The
      sensing electrodes are fabricated by sputtering a layer of SiO(2)-LiO(2)-BaO
      TiO(2)-La(2)O(3) (SLBTLO) onto platinum (Pt) electrodes and the pH value of the
      sample is evaluated by measuring the potential difference between the sensing
      electrodes and a reference electrode. Additionally, the integration of the
      microfluidic chip with a pneumatic fluid-control device facilitates automatic
      sample injection and a continuous sensing operation. The developed system
      provides a valuable tool with which to examine pH values in a wide range of
      biomedical and industrial applications.

PMID- 16099155
TI  - Amperometric biosensor for hydrogen peroxide based on ferrocene-bovine serum
      albumin and multiwall carbon nanotube modified ormosil composite.
AB  - A novel amperometric biosensor for hydrogen peroxide (H(2)O(2)) was developed by
      entrapping horseradish peroxidase (HRP) in a new ormosil composite doped with
      ferrocene monocarboxylic acid-bovine serum albumin conjugate and multiwall carbon
      nanotubes (MWNTs). The ormosil was prepared using 3-(aminopropyl)triethoxysilane
      and 2-(3,4 epoxycyclohexyl)-ethyltrimethoxy silane as monomers. The encapsulated
      conjugate showed excellent electrochemistry and acted as an electron transfer
      mediator. The presence of MWNTs improved the conductivity of the composite film.
      This matrix showed a biocompatible microenvironment for retaining the native
      activity of the entrapped HRP and a very low mass transport barrier to the
      substrate, which provided a fast amperometric response to H(2)O(2). The proposed
      H(2)O(2) biosensor exhibited a linear range of 0.02-4.0 mM with a detection limit
      of 5.0 microM (S/N = 3) and a K(M)(app) value of 2.0 mM. It could be used for
      flow injection analysis of hydrogen peroxide with a liner range from 0.02 to 4.5
      mM, sensitivity of 0.042 microA/mM and analytical time of 20 s per sample. This
      biosensor possessed good analytical performance and storage stability.

PMID- 16099156
TI  - Cardiomyocyte differentiation from embryonic and adult stem cells.
AB  - In recent years multiple reports indicating that embryonic as well as adult stem
      cells can differentiate to cardiomyocytes have ignited discussions on whether
      these stem cells could lead to new therapies for patients with heart disease.
      Recent developments have been made in the generation of cardiomyocytes from both
      embryonic and adult stem cells, and progress towards clinical applications in
      patients with heart failure has been made. Nevertheless, controversies
      surrounding safety and transdifferentiation issues will need to be overcome
      before these stem cell approaches can reach their full potential.

PMID- 16099157
TI  - Culture development for human embryonic stem cell propagation: molecular aspects
      and challenges.
AB  - Basic fibroblast growth factor and members of the transforming growth factor-beta
      superfamily are important regulators of human embryonic stem cell (hESC) self
      renewal. Extensive cross-talk between the intracellular signaling pathways
      activated by these factors contributes to maintenance of the undifferentiated
      hESC state. Understanding the molecular regulation of hESC self-renewal will
      facilitate the design of improved systems for hESC propagation and provide a
      foundation for strategies to direct the differentiation of hESCs to clinically
      relevant cell types.

PMID- 16099158
TI  - Transcriptional regulation by human papillomaviruses.
AB  - Human papillomaviruses are the causative agent of cancers in stratified
      epithelial surfaces. They replicate in the upper parts of the epithelium, where
      cells would normally be dying to produce a cornified layer. Therefore, they need
      to inhibit or delay differentiation and stimulate cell cycle progression to
      create an environment conducive for replication of the viral genome. The
      alterations both in differentiation and in the cell cycle are achieved by the
      viral proteins E6 and E7, which modulate cellular transcription mainly through
      their effects on p53 and the retinoblastoma family.

PMID- 16099159
TI  - Genomic views of chromatin.
AB  - With the availability of complete genome sequences for a number of organisms, a
      major challenge has become to understand how chromatin and its epigenetic
      modifications regulate genome function. High-throughput microarray and sequencing
      technologies are being combined with biochemical and immunological enrichment
      methods to obtain genome-scale views of chromatin in a variety of organisms. The
      data pinpoint novel, genomic elements and expansive chromatin domains, and offer
      insight into the functions of histone modifications. In parallel, state-of-the
      art imaging techniques are being used to investigate higher-order chromatin
      organization, and are beginning to bridge our understanding of chromatin biology
      with that of chromosome structure.

PMID- 16099160
TI  - Adaptations in interlimb and intralimb coordination to asymmetrical loading in
      human walking.
AB  - The purpose of this study was to examine both the intralimb (within a limb) and
      interlimb (between the right and left limbs) adaptations that occur in response
      to a unilaterally applied leg load as subjects walked at their preferred walking
      speed. It was hypothesized that this adaptation would alter interlimb
      coordination while intralimb coordination remained invariant. Subjects (n = 12)
      were required to walk on a treadmill at preferred walking speed. Bilateral 3-D
      kinematic data were collected while a load placed on the leg was increased. Gait
      adaptations to leg-loading were assessed through changes in coordination patterns
      between specific limb couplings. Continuous relative phase (CRP) was used to
      evaluate changes in limb coordination under each experimental load condition
      compared to a no load baseline condition. Both changes in magnitude of CRP (root
      mean-square (RMS) analysis) as well as temporal changes in CRP across the stride
      cycle (cross-correlation) were assessed. Cross-Correlation values changed with
      load for all interlimb couplings assessed suggesting alterations in interlimb
      coordination across the stride cycle. CRP cross-correlation values were close to
      1.0 in all the intralimb couplings examined, showing a relative invariance in
      intralimb coordination. Coordination changes in RMS were also observed for the
      interlimb couplings. RMS changes were also observed in the intralimb couplings on
      the loaded side. It appears that gait adaptations to a unilaterally applied leg
      load appear both at the intralimb and interlimb level. However, the majority of
      changes did appear at the interlimb level, where CRP as assessed through both
      cross-correlation and RMS measures changed. This study supports previous results
      that suggested a tighter coupling exists at the intralimb level, leaving the
      majority of gait adaptations to occur at the interlimb level. The observed
      adaptation in differences between interlimb and intralimb coordination may
      provide insight into gait adaptations in pathological gait.

PMID- 16099161
TI  - Modulation of leg muscle activity and gait kinematics by walking speed and
      bodyweight unloading.
AB  - During rehabilitation, many patient groups are being trained using bodyweight
      supported treadmill training. However, little is known about modulation of time
      and distance parameters, joint movements and leg muscle EMG patterns by very low
      walking speeds or partial bodyweight unloading. We collected data from 20 healthy
      young volunteers who walked on a treadmill at walking speeds varying between 0.5
      and 5.0 km h(-1) (0.14-1.39 ms(-1)) and with 0%, 25%, 50% and 75% bodyweight
      unloading. We found that cadence and stride length were largely influenced by
      walking speed, while bodyweight unloading influenced these measures only at 75%.
      However, the relative duration of the gait phases changed largely only at walking
      speeds less than 2.5 km h(-1), but was influenced by all different bodyweight
      unloading conditions. Joint trajectories of knee and ankle joint, as well as leg
      muscle EMG activity patterns changed largely at walking speeds slower than 2.5 km
      h(-1) and with 75% bodyweight unloading. We concluded that the parameters we
      investigated changed minimally at walking speeds faster than 2.5 km h(-1) and
      bodyweight unloading conditions less than 50%. Therefore, standards for EMG
      activity and joint angle trajectories should only be compared when the training
      is done with velocities higher than 2.5 km h(-1) and less than 50% body weight
      unloading.

PMID- 16099162
TI  - Rosai-Dorfman disease of the central nervous system.
AB  - Rosai-Dorfman disease (RDD) is an idiopathic, non-neoplastic, lymphoproliferative
      disorder characterized by sinus histiocytosis and massive lymphadenopathy. When
      RDD involves the central nervous system the lesion simulates a meningioma.
      Histological and immunohistochemical confirmation is essential for a definitive
      diagnosis. In this paper, ten cases of RDD confined to the central nervous system
      are reported. Another case with orbital RDD was excluded. Nine cases involved the
      cranial cavity alone; in one, the cervical extradural region was also involved.
      Treatment consisted of surgical excision or biopsy. Histology and
      immunohistochemistry revealed a mixed cell population of predominantly mature
      histiocytes with evidence of emperipolesis and strong positivity for S100 protein
      in all cases. No recurrence was observed during follow up ranging from three
      months to eight years.

PMID- 16099163
TI  - Improved method of measurement for tritiated water standardization by internal
      gas proportional counting.
AB  - Tritiated water has been standardized by internal gas counting following its
      chemical reduction to tritiated hydrogen by using a new tritium generator and an
      improved method of measurement. This method is based on the equality between the
      molar activities of the tritiated water and the tritiated hydrogen and is valid
      only when the reduction yield is unitary. It is simpler and more accurate than
      the conventional method. Two samples of tritiated water from a sealed ampoule
      were measured by internal gas proportional counting using both the conventional
      method and the improved method of measurement. The obtained results demonstrated
      the validity of the improved method.

PMID- 16099164
TI  - Protonated adenine: tautomers, solvated clusters, and dissociation mechanisms.
AB  - Ab initio and density functional theory calculations at the B3-MP2 and CCSD(T)/6
      311 + G(3df,2p) levels of theory are reported that address the protonation of
      adenine in the gas phase, water clusters, and bulk aqueous solution. The
      calculations point to N-1-protonated adenine (1+) as the thermodynamically most
      stable cationic tautomer in the gas phase, water clusters, and bulk solution.
      This strongly indicates that electrospray ionization of adenine solutions
      produces tautomer 1+ with a specificity calculated as 97-90% in the 298-473 K
      temperature range. The mechanisms for elimination of hydrogen atoms and ammonia
      from 1+ have also been studied computationally. Ion 1+ is calculated to undergo
      fast migrations of protons among positions N-1, C-2, N-3, N-10, N-7, and C-8 that
      result in an exchange of five hydrogens before loss of a hydrogen atom forming
      adenine cation radical at 415 kJ mol(-1) dissociation threshold energy. The
      elimination of ammonia is found to be substantially endothermic requiring 376-380
      kJ mol(-1) at the dissociation threshold and depending on the dissociation
      pathway. The overall dissociation is slowed by the involvement of ion-molecule
      complexes along the dissociation pathways. The competing isomerization of 1+
      proceeds by a sequence of ring opening, internal rotations, imine flipping, ring
      closures, and proton migrations to effectively exchange the N-1 and N-10 atoms in
      1+, so that either can be eliminated as ammonia. This mechanism explains the
      previous N-1/N-10 exchange upon collision-induced dissociation of protonated
      adenine.

PMID- 16099165
TI  - Energetic ion bombardment of Ag surfaces by C60+ and Ga+ projectiles.
AB  - The ion bombardment-induced release of particles from a metal surface is
      investigated using energetic fullerene cluster ions as projectiles. The total
      sputter yield as well as partial yields of neutral and charged monomers and
      clusters leaving the surface are measured and compared with corresponding data
      obtained with atomic projectile ions of similar impact kinetic energy. It is
      found that all yields are enhanced by about one order of magnitude under
      bombardment with the C60+ cluster projectiles compared with Ga+ ions. In
      contrast, the electronic excitation processes determining the secondary ion
      formation probability are unaffected. The kinetic energy spectra of sputtered
      particles exhibit characteristic differences which reflect the largely different
      nature of the sputtering process for both types of projectiles. In particular, it
      is found that under C60+ impact (1) the energy spectrum of sputtered atoms peaks
      at significantly lower kinetic energies than for Ga+ bombardment and (2) the
      velocity spectra of monomers and dimers are virtually identical, a finding which
      is in pronounced contrast to all published data obtained for atomic projectiles.
      The experimental findings are in reasonable agreement with recent molecular
      dynamics simulations.

PMID- 16099166
TI  - Does double electron capture lead to the formation of biradicals? An ECD-SORI-CID
      study on lacticin 481.
AB  - We studied lacticin 481, a small lantibiotic with three lanthionine bridges, by
      electron capture dissociation (ECD) in a Fourier transform ion cyclotron
      resonance (FTICR) mass spectrometer. Following electron capture, very little
      fragmentation was observed, but species formed by nondissociative single and
      multiple electron capture were abundant. Ions formed by double electron capture
      were subjected to sustained off resonance irradiation collision induced
      dissociation (SORI-CID) to determine whether stable biradicals were formed. In
      the SORI-CID spectra of the ions formed by double electron capture, some, but
      minor, H* radical loss was observed, which was not observed at all for regularly
      protonated ions. A small part of the ions formed by double electron capture are
      thus long-lived biradicals. Apart from the observed H* loss, the SORI-CID spectra
      of ions that captured two electrons was similar to that of regularly protonated
      ions and quite different from the SORI-CID spectra of radical ions formed by
      single electron capture. This implies that recombination of the two radical sites
      is the dominant process in biradical lacticin 481 ions, at least on the time
      scale of our SORI-CID experiments.

PMID- 16099167
TI  - The cationization mechanism study of novel oligo (p-phenyleneethynylene)s.
AB  - Two series of new oligo(p-phenyleneethynylene)s (OPEs) O1-O4 and O5-O8, which
      have been proven to be one of the chief classes of molecules mainly used as the
      wires and other potential backbones of molecular electronic devices, have been
      synthesized by stepwise synthetic approach. The characterization of these
      oligomers was performed on MALDI TOF MS. Different cationization salts have been
      applied to investigate the ionization processes of these series of oligomers
      under MALDI conditions. The experimental results show that these oligomers
      display a strong tendency to undergo radical cationization and varied ionization
      efficiency with different cationization agents attributable to their difference
      in cationic diameters. Furthermore, we found that these two series of oligomers
      differed in ionization properties because of their different end-groups even when
      the same cationization agent was used.

PMID- 16099168
TI  - Structural characterization of sulfadiazine metabolites using H/D exchange
      combined with various MS/MS experiments.
AB  - Two major metabolites and one minor metabolite of sulfadiazine were found in pig
      manure, using a special combination of different MS techniques like parent and
      product ion scans, H/D exchange, accurate mass measurement, and MS/MS experiments
      with substructures. N4-acetylsulfadiazine and 4-hydroxysulfadiazine were
      identified as major metabolites. N4-acetylsulfadiazine could be verified by H/D
      exchange and comparison with product ion spectra of a synthetic reference
      compound. In the case of 4-hydroxysulfadiazine, the majority of possible isomers
      could be discounted after H/D exchange. Substructure-specific MS/MS experiments
      with fragment ions and comparison with product ion spectra of two references
      revealed the presence of 4-hydroxysulfadiazine. The minor metabolite was
      characterized to some degree using H/D exchange and tandem mass spectrometry in
      combination with a high-resolution time of flight mass spectrometer. The
      aminopyrimidine moiety contained an additional modification with a likely
      elemental composition of C2H4O and no further acidic hydrogen.

PMID- 16099170
TI  - Structure elucidation of degradation products of the antibiotic amoxicillin with
      ion trap MS(n) and accurate mass determination by ESI TOF.
AB  - Today, it is necessary to identify relevant compounds appearing in discovery and
      development of new drug substances in the pharmaceutical industry. For that
      purpose, the measurement of accurate molecular mass and empirical formula
      calculation is very important for structure elucidation in addition to other
      available analytical methods. In this work, the identification and confirmation
      of degradation products in a finished dosage form of the antibiotic drug
      amoxicillin obtained under stress conditions will be demonstrated. Structure
      elucidation is performed utilizing liquid chromatography (LC) ion trap MS/MS and
      MS3 together with accurate mass measurement of the molecular ions and of the
      collision induced dissociation (CID) fragments by liquid chromatography electro
      spray ionization time-of-flight mass spectrometry (LC/ESI-TOF).

PMID- 16099169
TI  - Peptide mass mapping of acetylated isoforms of histone H4 from mouse
      lymphosarcoma cells treated with histone deacetylase (HDACs) inhibitors.
AB  - The acetylated isoforms of histone H4 from mouse lymphosarcoma cells treated with
      HDAC inhibitors trichostatin A (TSA) and depsipeptide (DDP) were separated by
      acetic acid urea-polyacrylamide gel electrophoresis (AU-PAGE), in-gel digested,
      and analyzed by matrix assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) and liquid chromatography tandem mass spectrometry
      (LC-MS/MS). The acetylation pattern of histone H4 in mouse lymphosarcoma cells
      induced by TSA was established in which acetylation initially occurred at K16
      followed by K12 and then K8 and/or K5. An identical order of acetylation was
      found for cells treated with DDP.

PMID- 16099171
TI  - Gadolinium activates and sensitizes the vanilloid receptor TRPV1 through the
      external protonation sites.
AB  - Gadolinium is a recognized blocker of many types of cation channels, including
      several channels of the transient receptor potential (TRP) superfamily. In this
      study, we demonstrate that Gd(3+), in addition to its blocking effects, activates
      and potentiates the recombinant vanilloid receptor TRPV1 expressed in HEK293T
      cells. Whole-cell currents through TRPV1 were induced by Gd(3+) with a half
      maximal activation achieved at 72 microM at +40 mV. Gd(3+), at concentrations up
      to 100 microM, lowered the threshold for heat activation and potentiated the
      currents induced by capsaicin (1 microM) and low extracellular pH (6). Higher
      concentrations of Gd(3+) (>300 microM) blocked the TRPV1 channel. Neutralizations
      of the two acidic residues, Glu600 and Glu648, which are the key residues
      conferring the proton-sensitivity to TRPV1, resulted in a loss of Gd(3+)-induced
      activation and/or a reduction in its potentiating effects. A trivalent
      nonlanthanide, Al(3+), that possesses much a smaller atomic mass than Gd(3+)
      blocked but did not activate or sensitize the TRPV1 channel. These findings
      indicate that Gd(3+) activates and potentiates the TRPV1 by neutralizing two
      specific proton-sensitive sites on the extracellular side of the pore-forming
      loop.

PMID- 16099172
TI  - Role of the peripheral benzodiazepine receptor in sensory neuron regeneration.
AB  - Peripheral benzodiazepine receptor (PBR) expression increases in small dorsal
      root ganglion (DRG) sensory neurons after peripheral nerve injury. To determine
      the functional significance of this induction, we evaluated the effects of PBR
      ligands on rodent sensory axon outgrowth. In vitro, Ro5-4864, a PBR agonist,
      enhanced outgrowth only of small peripherin-positive DRG neurons. When DRG cells
      were preconditioned into an active growth state by a prior peripheral nerve
      injury Ro5-4864 augmented and PK 11195, a PBR antagonist, blocked the injury
      induced increased outgrowth. In vivo, Ro5-4864 increased the initiation of
      regeneration after a sciatic nerve crush injury and the number of GAP-43-positive
      axons in the distal nerve while PK 11195 inhibited the enhanced growth produced
      by a preconditioning lesion. These results show that PBR has a role in the early
      regenerative response of small caliber sensory axons, the preconditioning effect,
      and that PBR agonists enhance sensory axon regeneration.

PMID- 16099173
TI  - EMG and MMG of agonist and antagonist muscles as a function of age and joint
      angle.
AB  - The aim of this study was to determine the effect of elbow joint position on
      electromyographic (EMG) and mechanomyographic (MMG) activities of agonist and
      antagonist muscles in young and old women. Surface EMG and MMG were recorded from
      the triceps and biceps brachii, and brachioradialis muscles during isometric
      elbow extensions in young and old women. The measurements were carried out at an
      optimal joint angle (A(o)), as well as at smaller (A(s) = A(o) - 30 degrees ) and
      larger (A(l) = A(o) + 30 degrees ) angles. The normalized to force EMG amplitude
      (RMS-EMG/F) was smaller in old women compared to young in all muscles. The RMS
      EMG/F of the triceps brachii muscle was not affected by muscle length while that
      of the biceps brachii and brachioradialis muscles increased at shortest muscle
      length in both groups. The normalized to force MMG amplitude (RMS-MMG/F) was
      smaller in old than in young in the triceps brachii muscle only. There was an
      increase in RMS-MMG/F with triceps brachii and biceps brachii muscle shortening
      in both groups, and in the brachioradialis muscle -- in young only. Compared to
      young, older women exhibited a bigger force fluctuation during maximum voluntary
      contraction, but these did not contribute significantly to the RMS-MMG. Skinfold
      thickness accounted for the RMS-EMG/F and RMS-MMG/F differences seen between old
      and young women in the biceps brachii muscle only. It is concluded that, the EMG
      and MMG response to muscles length change in agonist and antagonist muscles is
      generally similar in old and young women but the optimal angle shifts toward a
      bigger value in older women.

PMID- 16099174
TI  - Rethinking the ontogeny of mindreading.
AB  - We propose a mentalistic and nativist view of human early mental and social life
      and of the ontogeny of mindreading. We define the mental state of sharedness as
      the primitive, one-sided capability to take one's own mental states as mutually
      known to an interactant. We argue that this capability is an innate feature of
      the human mind, which the child uses to make a subjective sense of the world and
      of her actions. We argue that the child takes all of her mental states as shared
      with her caregivers. This allows her to interact with her caregivers in a
      mentalistic way from the very beginning and provides the grounds on which the
      later maturation of mindreading will build. As the latter process occurs, the
      child begins to understand the mental world in terms of differences between the
      mental states of different agents; subjectively, this also corresponds to the
      birth of privateness.

PMID- 16099175
TI  - Non-white noise in fMRI: does modelling have an impact?
AB  - The sources of non-white noise in Blood Oxygenation Level Dependent (BOLD)
      functional magnetic resonance imaging (fMRI) are many. Familiar sources include
      low-frequency drift due to hardware imperfections, oscillatory noise due to
      respiration and cardiac pulsation and residual movement artefacts not accounted
      for by rigid body registration. These contributions give rise to temporal
      autocorrelation in the residuals of the fMRI signal and invalidate the
      statistical analysis as the errors are no longer independent. The low-frequency
      drift is often removed by high-pass filtering, and other effects are typically
      modelled as an autoregressive (AR) process. In this paper, we propose an
      alternative approach: Nuisance Variable Regression (NVR). By inclusion of
      confounding effects in a general linear model (GLM), we first confirm that the
      spatial distribution of the various fMRI noise sources is similar to what has
      already been described in the literature. Subsequently, we demonstrate, using
      diagnostic statistics, that removal of these contributions reduces first and
      higher order autocorrelation as well as non-normality in the residuals, thereby
      improving the validity of the drawn inferences. In addition, we also compare the
      performance of the NVR method to the whitening approach implemented in SPM2.

PMID- 16099176
TI  - Therapy-related reorganization of language in both hemispheres of patients with
      chronic aphasia.
AB  - The brain processes of language recovery after stroke are poorly understood,
      partly because past research did not allow to differentiate the effects of
      spontaneous restitution processes from those of learning-related cortical
      reorganization. Here, we use a new approach offered by recently developed intense
      neuropsychological therapy methods, which allow for improving language functions
      within a short time period. Stroke patients with chronic aphasia received intense
      language therapy for 2 weeks and, over this period, improved their language
      performance as assessed using clinical tests. Neurophysiological activity
      elicited by words and pseudowords was measured before and after treatment. Over
      the therapy interval, early word evoked potentials (latency 250-300 ms) became
      significantly stronger whereas pseudoword responses did not change. Word-specific
      changes were documented by analyses of ERP amplitudes and root mean square
      values, which revealed interactions of the factors Assessment time (before vs.
      after therapy) and Wordness (word vs. pseudoword). Source localization using
      Minimum Norm Current Estimates showed that bilateral cortical sources activated
      by word stimuli contributed to the change, suggesting that neuronal networks
      distributed over both hemispheres are the substrate of cortical reorganization of
      language processing in intense aphasia therapy. Word-evoked differences in source
      strengths were significantly correlated with performance on a clinical language
      test, demonstrating a link between behavioral and neurophysiological changes. We
      suggest that the early word-evoked negativity might represent an index of
      reorganization of language after stroke and thus an aphasia recovery potential.

PMID- 16099177
TI  - Dynamic modulation of the primary somatosensory cortex during seeing and feeling
      a touched hand.
AB  - Previous work has demonstrated cross-modal links between vision and
      somatosensation at an early stage of sensory processing. Furthermore, recent
      behavioral studies have shown that viewing the stimulated body part can enhance
      tactile discrimination ability at the stimulated site. This study aims to
      investigate the role of the primary somatosensory cortex (SI) during visuotactile
      integration processes. Subjects looked at a hand in a video being touched on the
      first digit (D1) in synchrony with felt touches on their real hidden hand as
      compared with watching a video with asynchronous touches. During synchronous
      stimulation, subjects reported to feel the tactile sensation on the video hand,
      thus indicating that in this condition the subjects regarded the video hand as
      their own touched hand. This feeling disappeared in the asynchronous condition.
      Using neuromagnetic source imaging, we assessed the topography of the functional
      organization of SI related to tactile stimulation of D1. The cortical
      representation of D1 moved to a more inferior location during synchronous in
      comparison to asynchronous stimulation and rest. This modulation of the map in SI
      was significantly positively correlated with the feeling that the seen touch in
      the video represented the touch on the real hand. Thus, only if the seen touch is
      attributed to the own body, SI seems to be modulated.

PMID- 16099178
TI  - Comparison of fMRI motion correction software tools.
AB  - Motion correction of fMRI data is a widely used step prior to data analysis. In
      this study, a comparison of the motion correction tools provided by several
      leading fMRI analysis software packages was performed, including AFNI, AIR,
      BrainVoyager, FSL, and SPM2. Comparisons were performed using data from typical
      human studies as well as phantom data. The identical reconstruction,
      preprocessing, and analysis steps were used on every data set, except that motion
      correction was performed using various configurations from each software package.
      Each package was studied using default parameters, as well as parameters
      optimized for speed and accuracy. Forty subjects performed a Go/No-go task (an
      event-related design that investigates inhibitory motor response) and an N-back
      task (a block-design paradigm investigating working memory). The human data were
      analyzed by extracting a set of general linear model (GLM)-derived activation
      results and comparing the effect of motion correction on thresholded activation
      cluster size and maximum t value. In addition, a series of simulated phantom data
      sets were created with known activation locations, magnitudes, and realistic
      motion. Results from the phantom data indicate that AFNI and SPM2 yield the most
      accurate motion estimation parameters, while AFNI's interpolation algorithm
      introduces the least smoothing. AFNI is also the fastest of the packages tested.
      However, these advantages did not produce noticeably better activation results in
      motion-corrected data from typical human fMRI experiments. Although differences
      in performance between packages were apparent in the human data, no single
      software package produced dramatically better results than the others. The
      "accurate" parameters showed virtually no improvement in cluster t values
      compared to the standard parameters. While the "fast" parameters did not result
      in a substantial increase in speed, they did not degrade the cluster results very
      much either. The phantom and human data indicate that motion correction can be a
      valuable step in the data processing chain, yielding improvements of up to 20% in
      the magnitude and up to 100% in the cluster size of detected activations, but the
      choice of software package does not substantially affect this improvement.

PMID- 16099180
TI  - Do clinical variables predict an abnormal EEG in patients with complex febrile
      seizures?
AB  - PURPOSE: Febrile seizures are the commonest convulsive event in children younger
      than 5 years of age (incidence of 2-5%). Electroencephalography (EEG) is not
      indicated in the work up of simple febrile seizures. Information about its role
      in the assessment of complex febrile seizures (CFSs) is unclear and EEGs are
      frequently ordered. This study was designed to assess utility of clinical
      variables at presentation in predicting the likelihood of an abnormal EEG.
      METHODS: EEG requisitions, EEG reports, clinic charts and medical records over an
      11-year period (1990--2001) were retrospectively reviewed. The relationship
      between clinical variables like age, timing of the EEG since CFS, family history
      of seizures, neurological assessment and EEG abnormalities was statistically
      analyzed. RESULTS: One hundred and seventy-five children were included in the
      study. Of these 39.43% had EEG abnormalities. Children with a normal EEG were
      younger than those with an abnormal EEG (mean age 15.72 months versus 19.75
      months, p<0.05). Using multivariate analysis, factors predictive of abnormal EEGs
      in children with CFS were; age >3 years (p=0.010; 95% CI: 1.5--18.8), EEGs
      performed within 7 days (p=0.00; 95% CI: 1.78--7.12) and an abnormal neurological
      exam (p=0.053; 95% CI: 0.98--16.9). A family history of febrile seizures was more
      likely to be associated with a normal EEG (p=0.01; 95% CI: 0.04--0.60).
      CONCLUSIONS: Clinical variables at presentation can be used to screen children
      with CFS for whom an EEG is considered. This may lead to better use of resources.
      Whether abnormal EEG translates to future recurrences or epilepsy needs a
      prospective study.

PMID- 16099179
TI  - Left temporo-limbic and orbital dysfunction in schizophrenia during odor
      familiarity and hedonicity judgments.
AB  - Impairments of olfactory processing in patients with schizophrenia (SZ) have been
      reported in various olfactory tasks such as detection, discrimination,
      recognition memory, identification, and naming. The purpose of our study was to
      determine whether impairments in odor familiarity and hedonicity judgments
      observed in SZ patients during a previous behavioral study are associated with
      modifications of the activation patterns in olfactory areas. Twelve SZ patients,
      and 12 healthy comparison (HC) subjects, were tested using the H2(15)O-PET
      technique and 48 different odorants delivered during 8 scans. In addition to an
      odorless baseline condition, they had either to detect odor, or to judge odor
      familiarity or hedonicity, giving their responses by pressing a button. Regional
      cerebral blood flows during olfactory conditions were compared with those for
      baseline condition. Between-group analyses were then performed, and completed by
      regions of interest analyses. Both groups had equivalent ability for the
      detection of suprathreshold odorants, but patients found odors less familiar, and
      pleasant odors less pleasant than HC subjects. These behavioral results were
      related to functional abnormalities in temporo-limbic and orbital olfactory
      regions lateralized in the left hemisphere: the posterior part of the piriform
      cortex and orbital regions for familiarity judgments, the insular gyrus for
      hedonicity judgments, and the left inferior frontal gyrus and anterior piriform
      cortex/putamen region for the three olfactory tasks. They mainly resulted from a
      lack of activation during task conditions in the SZ patients. These data could
      explain olfactory disturbances and other clinical features of schizophrenia such
      as anhedonia.

PMID- 16099181
TI  - Expression and localization of myotonic dystrophy protein kinase in human
      skeletal muscle cells determined with a novel antibody: possible role of the
      protein in cytoskeleton rearrangements during differentiation.
AB  - Myotonic dystrophy is a multisystemic disorder, due to a CTG triplet expansion at
      the 3'UTR of the DM1 gene encoding for myotonic dystrophy protein kinase. Recent
      studies indicate that decreased DMPK levels could account for part of the
      symptoms suggesting a role of this protein in skeletal muscle differentiation. To
      investigate this aspect, polyclonal antibodies were raised against two peptides
      of the catalytic domain and against the human full-length DMPK (DMFL). In western
      blots, anti-hDMFL antibody was able to detect low amounts of purified human
      recombinant protein and recognized the splicing isoforms in heart and stomach of
      overexpressing mice. In human muscle extracts, this antibody specifically
      recognized a protein of apparent molecular weight of 85 kDa and it specifically
      stained neuromuscular junctions in skeletal muscle sections. In contrast, both
      anti-peptide antibodies demonstrated low specificity for either denatured or
      native DMPK, suggesting that these two epitopes are probably cryptic sites. Using
      anti-hDMFL, the expression and localization of DMPK was studied in human skeletal
      muscle cells (SkMC). Western blot analysis indicated that the antibody recognizes
      a main protein of apparent MW of 75 kDa, which appears to be expressed during
      differentiation into myotubes. Immunolocalization showed low levels of DMPK in
      the cytoplasm of undifferentiated cells; during differentiation the staining
      became more intense and was localized to the terminal part of the cells,
      suggesting that DMPK might have a role in cell elongation and fusion.

PMID- 16099183
TI  - MyoD and the transcriptional control of myogenesis.
AB  - The basic helix-loop-helix myogenic regulatory factors MyoD, Myf5, myogenin and
      MRF4 have critical roles in skeletal muscle development. Together with the Mef2
      proteins and E proteins, these transcription factors are responsible for
      coordinating muscle-specific gene expression in the developing embryo. This
      review highlights recent studies regarding the molecular mechanisms by which the
      muscle-specific myogenic bHLH proteins interact with other regulatory factors to
      coordinate gene expression in a controlled and ordered manner.

PMID- 16099182
TI  - Enhancement of growth and survival and alterations in Bcl-family proteins in beta
      thalassemic erythroid progenitors by novel short-chain fatty acid derivatives.
AB  - Accelerated apoptosis of erythroid progenitors is a characteristic of beta
      thalassemia which presents a significant barrier to definitive therapeutic
      approaches utilizing induction of endogenous fetal globin gene expression. gamma
      globin gene expression may not be inducible in, or may not be able to rescue,
      erythroid cells in which programmed cell death is initiated early in erythroblast
      development. In this report, short-chain fatty acid derivatives (SCFADs) which
      induce fetal globin gene expression were tested for their ability to promote
      proliferation and survival of erythroid progenitors cultured from beta
      thalassemic subjects, and of cytokine-dependent erythroid cell lines. Certain
      SCFADs promoted thalassemic Bfu-e growth and cytokine-independent growth and
      survival of erythroid cell lines. A 40-80% increase in erythroid Bfu-e colony
      number was observed in cultures established with any of five mitogenic SCFADs,
      compared to control or butyrate-treated cultures from the same subjects.
      Immunoblot analysis demonstrated that these same SCFADs also regulated the
      expression of specific protein inhibitors of apoptosis. Anti-apoptotic ratios of
      the proteins Bcl-xL/Bcl-xS in thalassemic Bfu-e were increased by 30-120% with
      exposure to the SCFDs, compared to the ratios in the same cells cultured under
      control conditions. Similar anti-apoptotic increases in Mcl-1L/Mcl-1S ratios were
      induced by the SCFADs. These findings suggest that select fetal globin-inducing
      SCFADs which enhance proliferation of beta-thalassemia progenitors may enhance
      survival of these progenitors by altering levels of Bcl-family protein members.
      This combination of effects should enhance erythroid cell survival in the beta
      thalassemia syndromes, allowing fetal globin gene expression to be induced more
      effectively than currently available, growth-suppressing, fetal globin-inducing
      agents, such as the butyrates or chemotherapeutic agents.

PMID- 16099184
TI  - Managing fatigue: it's about sleep.
AB  - Fatigue has increasingly been viewed by society as a safety hazard. This has lead
      to increased regulation of fatigue by governments. The most common control
      process has been compliance with prescriptive hours of service (HOS) rule sets.
      Despite the frequent use of prescriptive rule sets, there is an emerging
      consensus that they are an ineffective hazard control, based on poor scientific
      defensibility and lack of operational flexibility. In exploring potential
      alternatives, we propose a shift from prescriptive HOS limitations toward a
      broader Safety management system (SMS) approach. Rather than limiting HOS, this
      approach provides multiple layers of defence, whereby fatigue-related incidents
      are the final layer of many in an error trajectory. This review presents a
      conceptual basis for managing the first two levels of an error trajectory for
      fatigue. The concept is based upon a prior sleep/wake model, which determines
      fatigue-risk thresholds by the amount of sleep individuals have acquired in the
      prior 24 and 48 h. In doing so, managing level 1 of the error trajectory involves
      the implementation of systems that determine probabilistic sleep opportunity,
      such as prescriptive HOS rules or fatigue modelling. Managing level 2, requires
      individuals to be responsible for monitoring their own prior sleep and wake to
      determine individual fitness for duty. Existing subjective, neurobehavioral and
      electrophysiological research is reviewed to make preliminary recommendations for
      sleep and wake thresholds. However, given the lack of task- and industry-specific
      data, any definitive conclusions will rely in post-implementation research to
      refine the thresholds.

PMID- 16099185
TI  - Comparative analysis of 87,000 expressed sequence tags from the fumonisin
      producing fungus Fusarium verticillioides.
AB  - Fusarium verticillioides (teleomorph Gibberella moniliformis) is a pathogen of
      maize worldwide and produces fumonisins, a family of mycotoxins that have been
      associated with several animal diseases as well as cancer in humans. In this
      study, we sought to identify fungal genes that affect fumonisin production and/or
      the plant-fungal interaction. We generated over 87,000 expressed sequence tags
      from nine different cDNA libraries that correspond to 11,119 unique sequences and
      are estimated to represent 80% of the genomic complement of genes. A comparative
      analysis of the libraries showed that all 15 genes in the fumonisin gene cluster
      were differentially expressed. In addition, nine candidate fumonisin regulatory
      genes and a number of genes that may play a role in plant-fungal interaction were
      identified. Analysis of over 700 FUM gene transcripts from five different
      libraries provided evidence for transcripts with unspliced introns and spliced
      introns with alternative 3' splice sites. The abundance of the alternative splice
      forms and the frequency with which they were found for genes involved in the
      biosynthesis of a single family of metabolites as well as their differential
      expression suggest they may have a biological function. Finally, analysis of an
      EST that aligns to genomic sequence between FUM12 and FUM13 provided evidence for
      a previously unidentified gene (FUM20) in the FUM gene cluster.

PMID- 16099186
TI  - Active shielding of cylindrical saddle-shaped coils: application to wire-wound RF
      coils for very low field NMR and MRI.
AB  - We provide an exact expression for the magnetic field produced by cylindrical
      saddle-shaped coils and their ideal shield currents in the low-frequency limit.
      The stream function associated with the shield surface current is also
      determined. The results of the analysis are useful for the design of actively
      shielded radio-frequency (RF) coils. Examples pertinent to very low field nuclear
      magnetic resonance (NMR) and magnetic resonance imaging (MRI) are presented and
      discussed.

PMID- 16099187
TI  - Rotor-synchronized acquisition of quadrupolar satellite-transition NMR spectra:
      practical aspects and double-quantum filtration.
AB  - The very broad resonances of quadrupolar (spin I > 1/2) nuclei are resolved by
      magic angle spinning (MAS) into a large number of spinning sidebands, each of
      which often remains anisotropically broadened. The quadrupolar interaction can be
      removed to a first-order approximation if the MAS NMR spectrum is acquired in a
      rotor-synchronized fashion, aliasing the spinning sidebands onto a centreband and
      thereby increasing the signal-to-noise ratio in the resulting, possibly second
      order broadened, spectrum. We discuss the practical aspects of this rotor
      synchronization in the direct (t(2)) time domain, demonstrating that the
      audiofrequency filters in the receiver section of the spectrometer have a
      significant impact on the precise timings needed in the experiment. We also
      introduce a novel double-quantum filtered rotor-synchronized experiment for half
      integer spin quadrupolar (spin I = 3/2, 5/2, etc.) nuclei that makes use of
      central-transition-selective inversion pulses to both excite and reconvert double
      quantum coherences and yields a simplified spectrum containing only the ST(1)
      (m(I) = +/-1/2 <--> +/-3/2) satellite-transition lineshapes. For spin I = 5/2
      nuclei, such as (17)O and (27)Al, this spectrum may exhibit a significant
      resolution increase over the conventional central-transition spectrum.

PMID- 16099188
TI  - Chemostat culture characterization of Escherichia coli mutant strains
      metabolically engineered for aerobic succinate production: a study of the
      modified metabolic network based on metabolite profile, enzyme activity, and gene
      expression profile.
AB  - Various Escherichia coli mutant strains designed for succinate production under
      aerobic conditions were characterized in chemostat. The metabolite profiles,
      enzyme activities, and gene expression profiles were studied to better understand
      the metabolic network operating in these mutant strains. The most efficient
      succinate producing mutant strain HL27659k was able to achieve a succinate yield
      of 0.91 mol/mol glucose at a dilution rate of 0.1/h. This strain has the five
      following mutations: sdhAB, (ackA-pta), poxB, iclR, and ptsG. Four other strains
      involved in this study were HL2765k, HL276k, HL2761k, and HL51276k. Strain
      HL2765k has mutations in sdhAB, (ackA-pta), poxB and iclR, strain HL276k has
      mutations in sdhAB, (ackA-pta) and poxB, strain HL2761k has mutations in sdhAB,
      (ackA-pta), poxB and icd, and strain HL51276k has mutations in iclR, icd, sdhAB,
      (ackA-pta) and poxB. Enzyme activity data showed strain HL27659k has
      substantially higher citrate synthase and malate dehydrogenase activities than
      the other four strains. The data also showed that only iclR mutation strains
      exhibited isocitrate lyase and malate synthase activities. Gene expression
      profiles also complemented the studies of enzyme activity and metabolites from
      chemostat cultures. The results showed that the succinate synthesis pathways
      engineered in strain HL27659k were highly efficient, yielding succinate as the
      only major product produced under aerobic conditions. Strain HL27659k was the
      only strain without pyruvate accumulation, and its acetate production was the
      least among all the mutant strains examined.

PMID- 16099189
TI  - Impact of dissolved oxygen concentration on acetate accumulation and physiology
      of E. coli BL21, evaluating transcription levels of key genes at different
      dissolved oxygen conditions.
AB  - High density growth of Escherichia coli especially in large bioreactors may
      temporarily expose the cells to oxygen limitation as a result of a local
      inadequate oxygen supply or intermittently high concentrations of cells and
      nutrients. Although short, these periods can potentially alter bacterial
      metabolism, affecting both growth and recombinant proteins production capability,
      and thus lowering process productivity. When E. coli B (BL21), a lower acetate
      producing strain, was grown aerobically on high glucose, acetate accumulation was
      found to be inversely correlated to the dissolved oxygen (DO) levels, reaching 10
      g/L at 1%, 4 g/L at 6%, and zero at 30% DO concentration at stationary growth
      phase. Time-course transcription analysis of several genes involved in glucose
      and acetate metabolism indicated that the enhanced acetate production at lower DO
      levels is the result of altered transcription of several key genes. These genes
      are: the acetate producing gene (poxB), the glyoxylate shunt gene (aceA), the
      acetate uptake gene (acs), the gluconeogensis and anaplerotic pathways genes,
      (pckA, ppsA, ppc, and sfcA), the TCA cycle gene (gltA), and the sigma factors 70
      and S (rpoD and rpoS). It is suggested that the catabolic repressor/activator Cra
      is responsible for the bacterial response to different oxygen levels. Oxygen
      limitation seems to repress the constitutive expression of the glyoxylate shunt
      and gluconeognesis. In this work, the concept of transition state is proposed to
      describe the bacterial response to the lower DO concentration.

PMID- 16099190
TI  - [Blood-transmitted viral infections among haemophiliacs in Tunisia].
AB  - In this work, we proposed to evaluate prevalences of hepatitis B and C viruses
      and Parvovirus B19 among 70 Tunisian haemophiliacs treated with clotting factors
      imported from Europe and/or locally produced cryoprecipitate; among them 6 (8.6%)
      are known HIV positive patients. HBs antigen, anti-HBc antibodies and anti
      Parvovirus B19 antibodies were detected in 7.1%, 52.9% and 91.8%, respectively.
      HCV prevalence, defined as positive ELISA with positive Immunoblot and/or PCR was
      50.0%. Prevalences of these viral infections in haemophiliacs are higher than
      prevalences detected among general population and in the control group of the
      study. HCV infection is less frequent in haemophiliacs born after 1985, the year
      of introduction of the inactivation procedures in the production of coagulation
      factors concentrates; it decreases more considerably after 1994, date of
      introduction of systematic screening of HCV among blood donors. In contrast,
      despite the inactivation of the factors concentrates and the systematic screening
      of the blood donations against HBs antigen, since 1973, the risk of HBV infection
      contamination remains high in the Tunisian haemophiliacs. The introduction in
      1995 of hepatitis B vaccination in the national schedule of new-born vaccination
      may resolve in the future the problem of HBV infection in haemophiliacs and in
      the other categories of the Tunisian population.

PMID- 16099191
TI  - The relative contributions of different skin layers to the mechanical behavior of
      human skin in vivo using suction experiments.
AB  - Although the mechanical behavior of the top layer of the skin, the epidermis, is
      an important consideration in several clinical and cosmetic applications, there
      are few reported studies on this layer. The in vivo mechanical behavior of the
      upper skin layer (here defined as epidermis and papillar dermis) was
      characterized using a combined experimental and modeling approach. The work was
      based on the hypothesis that experiments with different length scales represent
      the mechanical behavior of different skin layers. Suction measurements with
      aperture diameters of 1, 2 and 6 mm were combined with ultrasound and optical
      coherence tomography to study the deformation of the skin layers. The experiments
      were simulated for small displacements with a two-layered finite element model
      representing the upper layer and the reticular dermis. An identification method
      compared the experimental and numerical results to identify the material
      parameters of the model. For one subject the whole parameter estimation procedure
      was completed, leading to a stiffness of C(10,ul) = 0.11 kPa for the top-layer
      and C(10,rd) = 0.16 MPa for the reticular dermis. This unexpected, extreme
      stiffness ratio of the material parameters let to convergence problems of the
      finite element software for most of the individuals.

PMID- 16099192
TI  - Specifying and controlling the optical image on the human retina.
AB  - A review covering the trends that led to the current state of knowledge in the
      areas of: (a) schematic models of the eye, and the definition of the retinal
      image in terms of first-order optics; (b) the description of the actual image on
      the retina and methods for accessing and characterizing it; (c) available
      procedures for controlling the quality of the retinal image in defined
      situations; and (d) intra-receptoral optical effects that cause differences
      between the light distribution on the retinal surface and at the level of
      interaction with photopigment molecules.

PMID- 16099194
TI  - Chaperone-like activity of macrophage migration inhibitory factor.
AB  - Macrophage migration inhibitory factor is a ubiquitous multifunctional cytokine
      having diverse immunological and neuroendocrine properties. Although this protein
      is known to be released into the circulation from the secretory granules of
      anterior pituitary or directly from immune cells as a consequence of stress, its
      participation in heat stress-induced aggregation of proteins has not yet been
      reported. We provide here the first evidence that the macrophage migration
      inhibitory factor possesses chaperone-like properties. It was shown to exist in
      the form of a mixture of low and high molecular weight oligomers. At heat stress
      temperatures the large oligomers dissociate into monomers that bind and stabilize
      thermally denatured malate dehydrogenase and glycogen phosphorylase b and thus
      prevent aggregation of the model proteins. Similar chaperone-like effects were
      also observed in the presence of partially purified brain extract containing
      besides the macrophage migration inhibitory factor a number of ubiquitous
      hydrophobic low molecular weight proteins identified by N-terminal microsequence
      analysis. Being highly stable and hydrophobic, the macrophage migration
      inhibitory factor in combination with other proteins of similar properties may
      comprise a family of constitutively expressed "small chaperones" that counteract
      the early onset of stress, around physiological conditions, when heat shock
      proteins are not abundant.

PMID- 16099193
TI  - Testicular germ cell tumours: the paradigm of chemo-sensitive solid tumours.
AB  - Testicular germ cell tumours (TGCTs) are the most frequent solid malignant tumour
      in men 20-40 years of age and the most frequent cause of death from solid tumours
      in this age group. Up to 50% of the patients suffer from metastatic disease at
      diagnosis. The majority of metastatic testicular cancer patients, in contrast to
      most other metastatic solid tumours, can be cured with highly effective cisplatin
      based chemotherapy. From a genetic point of view, almost all TGCTs in contrast to
      solid tumours are characterised by the presence of wild type p53. High p53
      expression levels are associated with elevated Mdm2 levels and a loss of
      p21(Waf1/Cip1) expression suggesting a changed functionality of p53. Expression
      levels of other proteins involved in the regulation of cell cycle progression
      indicate a deregulated G1-S phase checkpoint in TGCTs. After cisplatin-induced
      DNA damage, the increasing levels of p53 lead to the trans-activation of a number
      of genes but not of p21(Waf1/Cip1), preferentially directing TGCT cells into
      apoptosis or programmed cell death, both via the mitochondrial and the death
      receptor apoptosis pathways. The sensitivity of TGCTs to chemotherapeutic drugs
      may lay in the susceptibility of germ cells to apoptosis. Taken together, this
      provides TGCT as a tumour type model to investigate and understand the molecular
      determinants of chemotherapy sensitivity of solid tumours. This review aims to
      summarise the current knowledge on the biological basis of cisplatin-induced
      apoptosis and response to chemotherapy in TGCTs.

PMID- 16099195
TI  - SEPALLATA gene diversification: brave new whorls.
AB  - SEPALLATA (SEP) genes form an integral part of models that outline the molecular
      basis of floral organ determination and are hypothesized to act as co-factors
      with ABCD floral homeotic genes in specifying different floral whorls. The four
      SEP genes in Arabidopsis function redundantly, but the extent to which SEP genes
      in other flowering plants function similarly is unknown. Using a recent 113-gene
      SEP phylogeny as a framework, we find surprising heterogeneity among SEP gene C
      terminal motifs, mRNA expression patterns, protein-protein interactions and
      inferred function. Although some SEP genes appear to function redundantly, others
      have novel roles in fruit maturation, floral organ specification and plant
      architecture, and have played a major role in floral evolution of diverse plants.

PMID- 16099196
TI  - Accuracy evaluation of direct navigation with an isocentric 3D rotational X-ray
      system.
AB  - Minimally invasive interventions are often performed under fluoroscopic guidance.
      Drawbacks of fluoroscopic guidance are the fact that the presented images are 2D
      projections and that both the patient and the clinician are exposed to radiation.
      Image-guided navigation using pre-interventionally acquired 3D MR or CT data is
      an alternative. However, this often requires invasive anatomical landmark-based,
      marker-based or surface-based image-to-patient registration. In this paper, a
      coupling between an image-guided navigation system and an intraoperative C-arm X
      ray device with 3D imaging capabilities (3D rotational X-ray (3DRX) system) that
      enables direct navigation without invasive image-to-patient registration on 3DRX
      volumes, is described and evaluated. The coupling is established in a one-time
      preoperative calibration procedure. The individual steps in the registration
      procedure are explained and evaluated. The acquired navigation accuracy using
      this coupling is approximately one millimeter.

PMID- 16099197
TI  - Depth perception by the active observer.
AB  - The connection between perception and action has classically been studied in one
      direction only: the effect of perception on subsequent action. Although our
      actions can modify our perceptions externally, by modifying the world or our view
      of it, it has recently become clear that even without this external feedback the
      preparation and execution of a variety of motor actions can have an effect on
      three-dimensional perceptual processes. Here, we review the ways in which an
      observer's motor actions--locomotion, head and eye movements, and object
      manipulation--affect his or her perception and representation of three
      dimensional objects and space. Allowing observers to act can drastically change
      the way they perceive the third dimension, as well as how scientists view depth
      perception.

PMID- 16099198
TI  - Bandwidths studied as a function of temperature in ammonium halides near Tlambda.
AB  - This study gives our analysis of the Raman bandwidths using the soft mode-hard
      mode coupling model applied to ammonium halides. The temperature dependence of
      our observed bandwidths for the nu5(174 cm-1) Raman mode of NH4Cl and nu5(177 cm
      1) Raman mode of NH4Br, is analyzed close to phase transitions. From our
      analysis, we obtain beta=0.13 as the values of the critical exponent for the
      order parameter in the first order phase region for the ammonium halides.

PMID- 16099199
TI  - Raman frequency shifts of an internal mode near the tricritical and second order
      phase transitions in NH4Cl.
AB  - This study gives our analysis for the frequency shifts of the v2 (1708 cm-1)
      Raman mode in NH4Cl close to its tricritical (P=1.6 kbar) and second order (P=2.8
      kbar) phase transitions. From our analysis, we extract the values of the critical
      exponent which describes the critical behavior of the Raman frequency shifts for
      this internal mode for the pressure conditions studied in NH4Cl. Our exponent
      value of alpha approximately 0.2 for the tricritical phase transition is close to
      the values of 1/16 (T<Tc) and 1/8 (T>Tc) for the specific heat, predicted from a
      3D Ising model. Our exponent values for the second order phase transition (P=2.8
      kbar) for T<Tc and T>Tc are comparable with those reported in earlier studies.

PMID- 16099200
TI  - Nurses' information management across complex health care organizations.
AB  - The purpose of this study was to describe the information management used by
      hospital and home care nurses for patients in need of continuing care after an
      episode of hospitalization. METHOD: A prospective descriptive design was used. In
      total 287 hospital nurses and 220 home care nurses were asked to complete a
      questionnaire before and after the hospital implemented nursing documentation
      integrated in the electronic patient record (EPR). RESULTS: Discrepancies between
      the policies expressed by the health care organizations and the authorities in
      formal documents and the information management used by the nurses were
      identified. Differences were also found between nurses in hospital and home care
      with regard to how they assessed the information management during patient
      admission, throughout the patient's hospital stay and at the patient's discharge.
      The perceived differences decreased, however, after the hospital introduced
      electronic nursing documentation. The study shows a need to contextualize and
      customize the information that nurses exchange. In addition technological
      problems with the lack of integrated EPR systems between the hospital and the
      home health care as well as different practice models in the two organizations
      entail complex information handling during a patient's trajectory through the
      health system.

PMID- 16099201
TI  - Evaluation of two dependency parsers on biomedical corpus targeted at protein
      protein interactions.
AB  - We present an evaluation of Link Grammar and Connexor Machinese Syntax, two major
      broad-coverage dependency parsers, on a custom hand-annotated corpus consisting
      of sentences regarding protein-protein interactions. In the evaluation, we apply
      the notion of an interaction subgraph, which is the subgraph of a dependency
      graph expressing a protein-protein interaction. We measure the performance of the
      parsers for recovery of individual dependencies, fully correct parses, and
      interaction subgraphs. For Link Grammar, an open system that can be inspected in
      detail, we further perform a comprehensive failure analysis, report specific
      causes of error, and suggest potential modifications to the grammar. We find that
      both parsers perform worse on biomedical English than previously reported on
      general English. While Connexor Machinese Syntax significantly outperforms Link
      Grammar, the failure analysis suggests specific ways in which the latter could be
      modified for better performance in the domain.

PMID- 16099202
TI  - Linking nursing care to medical diagnoses: heterogeneity of patient groups.
AB  - AIM: The new budget system for Dutch hospitals makes use of patient groups that
      are highly homogeneous in terms of diagnosis and treatment combinations (diagnose
      behandeling combinaties (DBC)). These DBCs are the Dutch DRG variants. The DBC
      mainly concerns medical care; nursing care is almost regarded as a constant
      factor. In this study the DBC is linked to the nursing minimum data set for The
      Netherlands (NMDSN), to explore the degree of homogeneity in terms of nursing
      care for patient groups that are homogeneous in terms of the DBC. METHOD: In nine
      Dutch hospitals, patient information was collected by means of the NMDSN. To
      answer the question, we performed a secondary data analysis on the NMDSN. First,
      groups were formed in terms of medical diagnoses as defined in the DBC. Next,
      explorative statistical analyses were used to form homogeneous groups in terms of
      nursing diagnoses. These groups were compared in terms of the nursing care
      interventions and in terms of medical diagnoses. FINDING: Some medical diagnoses
      seem to be homogeneous, others more heterogeneous in terms of nursing care.
      DISCUSSION AND CONCLUSION: Limitations in the study design hinder a firm
      conclusion. However, the results discourage the use of the medical DBC for
      nursing care.

PMID- 16099203
TI  - Family study in PBC as a clue to the possible involvement of genetic and
      environmental factors.

PMID- 16099204
TI  - The effects of serum estrogen levels on hypoxemia and blood nitric oxide levels
      in experimental hepatopulmonary syndrome.
AB  - BACKGROUND: : Hepatopulmonary syndrome (HPS) is a well-defined cause of hypoxemia
      in patients who have liver disease due to abnormal intrapulmonary vascular
      dilatation. The pulmonary symptoms of HPS are the result of oxygenation defects
      that occur as a result of acquired dilatations of the pulmonary blood vessels. In
      this study, we investigated the effects of estrogen and nitric oxide (NO) in
      experimental HPS, especially in intrapulmonary vascular dilatation. METHODS: :
      Fifty female Sprague-Dawley rats were used in this study. The animals were
      divided into five groups of 10. Group l (the control group): the common bile duct
      (CBD) was dissected but not ligated. Group 2 (the cirrhosis group): the CBD was
      ligated. Group 3 (the cirrhosis+oophorectomized group): the CBD was ligated and a
      bilateral oophorectomy performed. Group 4 (the cirrhosis+estrogen group): the CBD
      was ligated and exogenous estrogen (5000U/kg) given. Group 5 (the
      control+estrogen group): the CBD was dissected, but not ligated and exogenous
      estrogen (5000U/kg) given. A 5-week waiting period was observed for the
      development of cirrhosis and the rats' lungs and liver were taken for
      histopathological examination. Pulmonary vessel diameters were measured. The
      total bilirubin, direct bilirubin, alkaline phosphatase (ALP), estrogen and serum
      nitric oxide (NO) levels were measured. RESULTS: : The mean perialveolar vessel
      diameters were significantly higher in the cirrhotic rats (Groups 2, 3, and 4)
      than the control and control+estrogen administered groups. Again, when we
      compared the cirrhosis+oophorectomized group and the cirrhosis+estrogen group,
      the mean perialveolar vessel diameter was significantly lower in the
      cirrhosis+oophorectomized group than the cirrhosis+estrogen administered group
      (p=0.001). The mean perialveolar vessel diameter in the cirrhosis+oophorectomized
      group was significantly lower than the cirrhosis group (p=0.01). When we compared
      the cirrhotic rats (Groups 2, 3, and 4) and the control group, the plasma NO
      levels were significantly higher in the cirrhotic rats than the control group
      (p<0.001). Among the cirrhotic rats, the plasma NO levels were 47.2+/-0.7 and
      70.9+/-1.5mumol/l in the cirrhosis+oophorectomized group and the
      cirrhosis+estrogen administered group, respectively (p=0.004). CONCLUSIONS: : We
      consider that raised levels of estrogen have a potential role in intrapulmonary
      vascular dilatation and hypoxemia in HPS. Also, we consider that this effect of
      estrogen is due to increased levels of NO. Antiestrogenic surgical therapy may
      decrease the serum estrogen and NO levels, and may decrease the diameter of
      perialveolar vessels in order to relieve hypoxia in cirrhotic cases.

PMID- 16099205
TI  - Intron 2 [IVS2, T-C +4] HFE gene mutation associated with S65C causes alternative
      RNA splicing and is responsible for iron overload.
AB  - A patient with congenital liver fibrosis revealed a high transferrin saturation
      index and iron overload on liver biopsy. He did not carry the most frequent HFE
      mutations: C282Y or H63D. Heterozygosity was detected for S65C. Unknown HFE
      mutations were also sought using a combined denaturing high performance liquid
      chromatography (DHPLC)/direct sequence approach and another point mutation, a
      transition T-C (nt 4910), at the fourth base of the donor splice site of intron 2
      [HFE, intervening sequence (IVS) 2, T-C +4] was found. Family screening revealed
      that a daughter carried both S65C and [IVS2, T-C +4]. CONCLUSION: : The existence
      in our proband of a partly-altered HFE protein in the region encoded by exon 2
      might be responsible for the histologically-demonstrated iron overload.

PMID- 16099206
TI  - In vitro polyphenol effects on activity, expression and secretion of pancreatic
      bile salt-dependent lipase.
AB  - The relationship between cholesterol and atherosclerosis has gained wide credence
      and red wine polyphenols have been shown to have an anti-atherogenic activity. In
      the present in vitro studies, we have evaluated and compared the effects of
      resveratrol, an active compound of red wine, and of a whole red wine polyphenolic
      extract (RWE) on the pancreatic bile salt-dependent lipase (BSDL). BSDL is
      involved in the duodenal hydrolysis of lipid esters and in part of cholesteryl
      esters thus favoring the bioavailability of free cholesterol. Resveratrol and RWE
      decrease the human and rat enzyme activities. Resveratrol and RWE also impaired
      the secretion of BSDL by the rat pancreatic AR4-2J cells used as secreting model.
      This effect is reversed by the removal of resveratrol or RWE from the cell
      culture medium. Further, resveratrol (but not RWE) affects the transcription of
      the gene encoding BSDL and dramatically diminishes the quantity of the enzyme
      that is expressed and secreted by AR4-2J cells. Results suggest that the
      hypolipemic effects of red wine polyphenols could partly originate from the
      inhibition of BSDL activity and secretion in the duodenum. In vivo, these effects
      could decrease the hydrolysis of dietary lipid esters and likely the absorption
      of free cholesterol.

PMID- 16099207
TI  - Phospholipase D in the signaling networks of plant response to abscisic acid and
      reactive oxygen species.
AB  - Phospholipase D (PLD) has been implicated in different cellular processes in
      plant growth, development, and stress responses. Recent results have provided
      insights into the molecular mechanism by which PLD and its lipid product
      phosphatidic acid (PA) participate in cell signaling. Effector proteins that have
      been identified for PLD and PA in plants include a heterotrimeric G protein,
      protein phosphatase, and protein kinase. Evidence has been presented for a direct
      link from a PLD, PA, to a target protein in specific physiological processes. PLD
      and PA play multiple roles in the signaling networks of plant response to
      abscisic acid and reactive oxygen species.

PMID- 16099208
TI  - Lipoprotein-mediated lipid transport in insects: analogy to the mammalian lipid
      carrier system and novel concepts for the functioning of LDL receptor family
      members.
AB  - In all animals, lipoproteins are used to transport lipids through the aqueous
      circulation. Lipids are delivered to mammalian cells by two different mechanisms:
      via endocytic uptake of the complete lipoprotein particle mediated by members of
      the low density lipoprotein (LDL) receptor (LDLR) family, or by selective
      delivery of lipoprotein-carried lipids at the cell surface, such as lipid uptake
      following the action of a lipoprotein lipase. Although many structural elements
      of the lipid transport system of insects are similar to those of mammals, insect
      lipoprotein-mediated lipid transport was thought to apply only to the latter
      concept, since the single lipoprotein acts as a reusable lipid shuttle. However,
      the recent identification of lipoprotein receptors of the LDLR family in insects
      suggests that lipid transport in these animals may also adopt the first concept.
      Yet, the endocytic properties of the insect LDLR homologue appear to deviate from
      those of the mammalian LDLR family members, resulting in the recycling of
      endocytosed lipoprotein in a transferrin-like manner. This indicates that a
      hitherto unknown as well as unexpected function can be added to the plethora of
      functions of LDLR family members. Analysis of the molecular mechanism of the
      ligand-recycling function of the insect receptor provides also new insight into
      the possible functioning of the mammalian family members. In the last several
      years, mammalian and insect lipoprotein-mediated lipid transport systems have
      been reviewed separately with respect to functioning and lipid delivery. This
      review, in which new and important developments in the insect field with respect
      to our understanding of lipid delivery are discussed with a particular focus on
      the involvement of the LDLR homologue, aims at comparing the two systems, also
      from an evolutionary biological perspective, and proposes that the two systems
      are more similar than assumed previously.

PMID- 16099209
TI  - Isohumulones modulate blood lipid status through the activation of PPAR alpha.
AB  - Isohumulones derived from hops are the major bitter compounds in beer. It was
      recently reported that isohumulones activated peroxisome proliferator-activated
      receptors (PPARs) alpha and gamma in vitro and modulated glucose and lipid
      metabolism in vivo. In this study, we examined the effects of isomerized hop
      extract (IHE) primarily containing isohumulones in C57BL/6N male mice and found
      that such treatment increased their liver weight and reduced their plasma
      triglyceride and free fatty acid levels. Microarray analysis and quantitative
      real time PCR (QPCR) showed that IHE dose-dependently upregulated the expression
      of a battery of hepatic genes that are involved in microsomal omega-oxidation and
      peroxisomal and mitochondrial beta-oxidation. These effects were common in both
      genders and very similar to those found with the PPARalpha agonist, fenofibrate
      (FF). Moreover, these effects were not found in PPARalpha-deficient mice. Thus,
      our results strongly suggest that IHE intake upregulates the expression of key
      genes that are involved in hepatic fatty acid oxidation, and that it ameliorates
      the blood lipid profile by activating PPARalpha.

PMID- 16099210
TI  - Detecting temporal lobe seizures from scalp EEG recordings: a comparison of
      various features.
AB  - OBJECTIVE: Sixteen different features are evaluated in their potential ability to
      detect seizures from scalp EEG recordings containing temporal lobe (TL) seizures.
      Features include spectral measures, non-linear methods (e.g. zero-crossings),
      phase synchronization and the recently introduced Brain Symmetry Index (BSI).
      Besides an individual comparison, several combinations of features are evaluated
      as well in their potential ability to detect TL seizures. METHODS: Sixteen long
      term scalp EEG recordings, containing TL seizures from patients suffering from
      temporal lobe epilepsy (TLE), were analyzed. For each EEG, all 16 features were
      determined for successive 10s epochs of the recording. All epochs were labeled by
      experts for the presence or absence of seizure activity. In addition, triplet
      combinations of various features were evaluated using pattern recognition tools.
      Final performance was evaluated by the sensitivity and specificity (False Alarm
      Rate (FAR)), using ROC curves. RESULTS: In those TL seizures characterized by
      unilateral epileptiform discharges, the BSI was the best single feature. Except
      for one low-voltage EEG with many artifacts, the sensitivity found ranged from
      0.55 to 0.90 at a FAR of approximately 1/h. Using three features increased the
      sensitivity to 0.77-0.97. In patients with bilateral electroencephalographic
      changes, the single best feature most often found was a measure for the number of
      minima and maxima (mmax) in the recording, yielding sensitivities of
      approximately 0.30-0.96 at FAR approximately 1/h. Using three features increased
      the sensitivity to 0.38-0.99, at the same FAR. In various recordings, it was even
      possible to obtain sensitivities of 0.70-0.95 at a FAR = 0. CONCLUSIONS: The
      Brain Symmetry Index is the most relevant individual feature to detect
      electroencephalographic seizure activity in TLE with unilateral epileptiform
      discharges. In patients with bilateral discharges, mmax performs best. Using a
      triplet of features significantly improves the performance of the detector.
      SIGNIFICANCE: Improved seizure detection can improve patient care in both the
      epilepsy monitoring unit and the intensive care unit.

PMID- 16099211
TI  - Reproducibility of measures of neurophysiological activity in Wernicke's area: a
      magnetic source imaging study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the reproducibility of
      estimates of neurophysiological activity obtained with Magnetic Source Imaging.
      METHODS: Split-half data sets were obtained from 14 healthy volunteers during
      performance of a continuous recognition task for spoken words. The concurrent
      validity of spatiotemporal activation maps obtained with this task has been
      previously verified through comparisons with the Wada test and electrocortical
      stimulation mapping. Consecutive late activity sources (> 200 ms after stimulus
      onset) were modeled independently as equivalent current dipoles (ECDs) and used
      to identify the location of language-specific cortex in the left hemisphere
      (Wernicke's area). RESULTS: Linear displacement of the geometric center of the
      cluster of ECDs in this region ranged between 2 and 8 mm across subjects.
      Intraparticipant variability (range) in the onset latency of activity was +/-50
      ms, while the range of change in global field power for the entire set of ECDs in
      Wernicke's area was less than 17% in all cases. CONCLUSIONS: The results indicate
      that despite its many conceptual limitations the ECD model can provide reliable
      estimates of regional cortical activity associated with the engagement of
      linguistic processes. SIGNIFICANCE: The results highlight the need for
      reproducibility studies when research questions pose particular requirements for
      precision of estimates of regional neurophysiological activity.

PMID- 16099212
TI  - Separation of the components of the late positive complex in an ERP
      dishabituation paradigm.
AB  - OBJECTIVE: A substantial body of evidence shows that several separate components
      underlie the late positive complex (LPC) of the ERP. Each of these has been
      proposed as a possible neural index of the orienting reflex (OR), but none has
      clearly met the criteria required for identification as an OR. The skin
      conductance response (SCR) is the most extensively examined index of the OR, and
      was used here as an OR 'yard-stick'. The primary aim of this study was to
      determine if any of the components of the LPC show stimulus-response
      relationships analogous to those of the SCR. METHODS: ERPs and SCRs were
      simultaneously recorded from 72 subjects during an ERP dishabituation paradigm,
      in which a habituation stimulus (S1) was presented for a series of trials, during
      which a different stimulus (S2) was interpolated. This sequence was presented in
      a series of trains, allowing across-train LPC and SCR exploration as a function
      of trial. The sensitivity of these components to stimulus intensity and
      significance, other stimulus dimensions important in defining the OR, was also
      examined. We utilised a PCA with varimax rotation to separate the ERP components
      underlying the LPC. RESULTS: Four factors extracted appeared to correspond to the
      classic Slow Wave, the P3b, the Novelty P3 and the P3a. While the LPC exhibited a
      stimulus-response relationship analogous to the SCR, each of the separate
      components was differentially sensitive to aspects of the stimulus manipulations
      examined here. CONCLUSIONS: This study has demonstrated that the LPC is an
      adequate EEG index of the OR. However, the underlying components of the LPC
      examined here--which we consider to be the classic slow wave, P3b, Novelty P3 and
      P3a--cannot be used interchangeably as OR indices. SIGNIFICANCE: This study
      clarifies links between the autonomic OR and its CNS correlates.

PMID- 16099214
TI  - Neuroimaging the sleep disordered patient: a commentary.

PMID- 16099215
TI  - Effects of rest-duration, time-of-day and their interaction on periodic leg
      movements while awake in restless legs syndrome.
AB  - BACKGROUND AND PURPOSE: The diagnostic criteria for restless legs syndrome (RLS)
      indicate that both time-of-day and rest effects induce or aggravate symptoms.
      Periodic limb movements while awake (PLMW) provide an objective motor sign of RLS
      that can be measured during an awake suggested immobilization test (SIT). This
      study uses the SIT at different times of the day and analyzes time-of-day and
      duration-of-rest effects and their interaction on the PLMW. PATIENTS AND METHODS:
      Twenty-eight RLS patients who were not on medications had SIT tests at 10 pm, 8
      am and 4 pm on two consecutive days. PLMW for each 20-min period were analyzed
      for time-of-day and rest effects and their interaction. PLMW increase from the
      first to last 20-min SIT period assessed the rest-effects. RESULTS: Significant
      effects were found for rest, time-of-day and rest-time-of-day interaction. The
      rest-effect increased most from morning to afternoon while total PLMW increased
      more from afternoon to night. Males compared to females had significantly more
      PLMW and a larger rest-effect change with time-of-day. CONCLUSIONS: Rest and time
      of-day effects and their interaction all increase RLS symptoms. PLMW increase
      with rest may provide a sensitive measure of symptom severity.

PMID- 16099216
TI  - What? Influenced by industry? Not me!

PMID- 16099218
TI  - Autophagy in innate and adaptive immunity.
AB  - Recently, several groups made a nearly simultaneous discovery that autophagic
      degradation represents a previously unrecognized effector of innate and adaptive
      immunity. Despite the fact that hints to these phenomena hail back to earlier
      sporadic reports, autophagy has, until now, received attention primarily as a
      fundamental cellular homeostasis pathway, whereby cytoplasm portions get
      sequestered by the membrane for delivery to lysosomes. This process leads to the
      removal of damaged or surplus organelles and digests stable, long-lived
      macromolecules. Autophagy has been implicated previously in both health-promoting
      and disease-associated states, in cancer, neurodegeneration, development and
      aging. A protective role has recently been demonstrated in infectious diseases,
      which represents a previously unrecognized immune mechanism acting against
      intracellular microbes. This review reviews autophagy as an immune mechanism.

PMID- 16099219
TI  - Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues.
AB  - Here, we review the biochemical and molecular properties of thymosin beta(4)
      (Tbeta(4)), the major actin-sequestering molecule in eukaryotic cells, and its
      key role in dermal- and corneal-wound healing. Tbeta(4) has several, novel,
      potential clinical applications in the repair and remodeling of ulcerated tissues
      and solid organs following hypoxic injuries, such as myocardial infarction and
      stroke. It might also have important repair functions in the pathophysiologic
      sequelae that are associated with actin toxicity and with septic shock, such as
      respiratory distress syndrome, multi-organ failure and severe tissue trauma.

PMID- 16099220
TI  - Estrogenic effects of environmental chemicals: an interspecies comparison.
AB  - The development of various in vitro screening methods has led to identification
      of novel estrogenic chemicals of natural and anthropogenic origin. In this study,
      the (anti)estrogenic potential of several environmental chemicals were compared
      in an array of in vitro test systems comprising: (i) competitive binding to
      estrogen receptors derived from the human breast cancer cell line MCF-7 (hER) and
      rainbow trout (Oncorhynchus mykiss) (rtER), (ii) a proliferation assay with MCF-7
      cells (E-SCREEN), and iii) induction of vitellogenin (rtVtg) in isolated rainbow
      trout hepatocytes. The results showed substantial differences in assay
      sensitivity for potent estrogens like 17beta-estradiol, diethylstilbestrol and
      zearalenone (ranking order of sensitivity: E-SCREEN > hER approximately rtER
      approximately rtVtg). Chemicals like 4-n-nonylphenol and bisphenol A had higher
      relative binding affinity to the hER, whereas 4-t-butylphenol and 4-n-butylphenol
      showed highest affinity to the rtER. Zearalenone and the novel estrogen 4-t
      butylhexanol displayed a considerable higher relative potency in the E-SCREEN
      than the rtVtg assay, whereas alkylphenols and the novel estrogen mimic 4-t-butyl
      nitrobenzene were most potent in fish cells. Correlation analysis of data from
      the test systems suggest that interspecies differences is largely due to inter
      assay variation of the ER-dependent cellular responses, whereas binding to the ER
      are fairly similar in the two species tested.

PMID- 16099221
TI  - AT1 receptor in paraventricular nucleus mediates the enhanced cardiac sympathetic
      afferent reflex in rats with chronic heart failure.
AB  - Our previous studies have shown that the cardiac sympathetic afferent reflex
      (CSAR) was enhanced in the chronic heart failure in dogs and rats. Exogenous
      angiotensin II (Ang II) in the paraventricular nucleus (PVN) potentiated this
      reflex which was mediated by AT1 receptor. The aim of the present study was to
      determine if the abnormal endogenous Ang II and AT1 receptor in the PVN were
      responsible for the enhanced CSAR in rats with coronary ligation-induced chronic
      heart failure (CHF). Under urethane and alpha-chloralose anesthesia, mean
      arterial pressure, heart rate and renal sympathetic nerve activity (RSNA) were
      recorded in sino-aortic denervated and cervical vagotomized CHF and sham-operated
      rats. The effects of bilateral microinjection of AT1 receptor antagonist losartan
      and angiotensin converting enzyme inhibitor captopril on the CSAR evoked by
      epicardial application of bradykinin (BK, 0.04 and 0.4 microg) were determined
      respectively. Both AT1 receptor mRNA and AT1 receptor protein in the PVN were
      measured. Bilateral microinjection of either captopril (10 nmol) or losartan (50
      nmol) into the PVN inhibited the enhanced CSAR evoked by BK in rats with CHF, but
      had no significant effects in sham-operated rats. AT1 receptor protein in the PVN
      significantly increased in CHF rats compared with sham-operated rats. These
      results indicated that either decrease of Ang II or blockage of AT1 receptor in
      the PVN normalized the enhanced CSAR evoked by epicardial application of BK in
      rats with CHF, and that increased expression of AT1 receptor in the PVN
      contributed to the enhanced CSAR in the CHF state.

PMID- 16099222
TI  - Rtg2 protein: at the nexus of yeast longevity and aging.
AB  - Firm support for the notion that metabolism and particularly mitochondrial
      metabolism plays a significant role in aging has been gathered in studies on
      yeast. As in other organisms, mitochondria contribute to aging through their
      propensity to generate reactive oxygen species. There is more to the involvement
      of mitochondria in aging than this, however. Mitochondrial dysfunction, which
      accumulates during aging, triggers the retrograde response, an intracellular
      signaling pathway that activates genes that compensate for this dysfunction. A
      key signaling protein in this pathway is the Rtg2 protein. Recent studies have
      provided evidence that this protein lies at the nexus of the four major processes
      that are involved in aging in yeast and in other organisms; namely, metabolism,
      stress resistance, chromatin-dependent gene regulation, and genome stability. The
      details of this central role of Rtg2 protein explain the delicate balance between
      longevity and aging, which ultimately must tip towards the latter. Phenomena that
      resemble the retrograde response appear to exist in human cells, with both common
      and cell type-specific gene expression changes as the output.

PMID- 16099223
TI  - Cerebrocrast promotes the cotransport of H+ and Cl- in rat liver mitochondria.
AB  - Considering that cerebrocrast stimulates oligomycin-inhibited state 3 respiration
      simultaneously with mitochondrial transmembrane potential (Deltapsi) dissipation,
      the mechanism underlying the uncoupler activity of cerebrocrast was assessed by
      its ability to permeabilize the mitochondrial inner membrane to H(+) or to K(+)
      or to cotransport anions with H(+). The partition coefficient of cerebrocrast in
      mitochondrial membrane and its ability to act as a membrane-active compound
      disturbing membrane lipid organization were also investigated. Cerebrocrast
      induced no permeabilization of mitochondrial inner membrane to H(+) or K(+), but
      it was able to transport H(+) in association with Cl(-). Cerebrocrast showed a
      strong incorporation into the mitochondrial membrane, with a partition
      coefficient (Kp(m/w)) of 2.7(+/-0.1)x10(5). Cerebrocrast also reduced, in a
      concentration dependent manner, the phase transition temperature, the cooperative
      unit size, and the enthalpy associated with the phase transition temperature of
      DMPC membrane bilayers. It was concluded that the uncoupler activity of
      cerebrocrast is due to its ability to promote the cotransport of H(+) with Cl(-)
      through the rat liver mitochondrial inner membrane, and that this cerebrocrast
      mechanism of action may be potentiated by alterations of membrane lipid
      organization and membrane lateral heterogeneity.

PMID- 16099224
TI  - Ablation of vagal preganglionic neurons innervating the extra-thoracic trachea
      affects ventilatory responses to hypercapnia and hypoxia.
AB  - This study tested the hypothesis that during hypercapnia or hypoxia, airway
      related vagal preganglionic neurons (AVPNs) of the nucleus ambiguus (NA) release
      acetylcholine (ACh), which in a paracrine fashion, activates ACh receptors
      expressed by inspiratory rhythm generating cells. AVPNs in the NA were ablated by
      injecting a saporin- (SA) cholera toxin b subunit (CTb-SA) conjugate into the
      extra-thoracic trachea (n=6). Control animals were injected with free CTb (n=6).
      In CTb treated rats, baseline ventilation and ventilatory responses to
      hypercapnia (5 and 12% CO(2) in O(2)) or hypoxia (8% O(2) in N(2)) were similar
      (p>0.05) prior to and 5 days after injection. CTb-SA injected rats maintained
      rhythmic breathing patterns 5 days post injection, however, tachypneic responses
      to hypercapnia or hypoxia were significantly reduced. The number of choline
      acetyltransferase (ChAT) immunoreactive cells in the NA was much lower (p<0.05)
      in CTb-SA rats as compared to animals receiving CTb only. These results suggest
      that AVPNs participate in the respiratory frequency response to hypercapnia or
      hypoxia.

PMID- 16099226
TI  - Towards an understanding of the structural molecular mechanism of beta(2)
      microglobulin amyloid formation in vitro.
AB  - Deriving a complete understanding of protein self-association into amyloid
      fibrils across multiple distance and time scales is an enormous challenge. At
      small length scales, a detailed description of the partially folded protein
      ensemble that participates in self-assembly remains obscure. At larger length
      scales, amyloid fibrils are often heterogeneous, can form along multiple
      pathways, and are further complicated by phenomena such as phase-separation. Over
      the last 5 years, we have used an array of biophysical approaches in order to
      elucidate the structural and molecular mechanism of amyloid fibril formation,
      focusing on the all beta-sheet protein, beta(2)-microglubulin (beta(2)m). This
      protein forms amyloid deposits in the human disease 'dialysis-related
      amyloidosis' (DRA). We have shown that under acidic conditions beta(2)m rapidly
      associates in vitro to form amyloid-like fibrils that have different
      morphological properties, but which contain an underpinning cross-beta structure.
      In this review, we discuss our current knowledge of the structure of these
      fibrils, as well as the structural, kinetic and thermodynamic relationship
      between fibrils with different morphologies. The results provide some of the
      first insights into the shape of the self-assembly free-energy landscape for this
      protein and highlight the parallel nature of the assembly process. We include a
      detailed description of the structure and dynamics of partially folded and acid
      unfolded species of beta(2)m using NMR, and highlight regions thought to be
      important in early self-association events. Finally, we discuss briefly how
      knowledge of assembly mechanisms in vitro can be used to inform the design of
      therapeutic strategies for this, and other amyloid disorders, and we speculate on
      how the increasing power of biophysical approaches may lead to a fuller
      description of protein self-assembly into amyloid in the future.

PMID- 16099227
TI  - Effect of intermittent compression therapy on bone mineral density in women with
      low bone mass.
AB  - Intermittent pneumatic compression has been shown to increase blood flow in the
      leg which, in turn, may improve BMD. We performed a pilot study to assess whether
      intermittent compression of the leg could improve BMD at the femoral neck. 37
      postmenopausal women with low bone density T score < -1 at either hip or spine
      were recruited into the study of whom 24 completed. Women applied intermittent
      compression for 2 h a day for 6 months to each leg in turn. The study lasted 1
      year. Women were also given daily 1 g of Calcium and 800 IU of vitamin D
      (Calcichew D 3 forte Shire, UK). Lumbar spine BMD decreased by 0.5% at 12 months
      compared with baseline (mean difference 0.005 g/cm(2), 95% C.I -0.2287 to
      0.03459, P = 0.28). At 12 months the right femoral neck BMD increased by 3%
      compared with baseline (mean 0.811 +/- 0.08, P = 0.22), while the left increased
      2% (0.783 +/- 0.06, P = 0.16). There was no change in BMD at the distal tibia or
      heels and no site effect of the compression. The fat mass decreased by 4.6% in
      the right leg and 5% in the left leg (P = 0.005 and 0.003, respectively). Tissue
      thickness did not change. The analysis of the interaction between the degree of
      exercise and change in BMD showed a statistically significant increase in right
      femoral neck BMD following 6 months of right leg intermittent compression, but
      only in women whose exercise was minimal (P = 0.029). This effect was not seen in
      the left femur possibly due to the reduced number of patients who completed the
      study in this group. These preliminary results indicate that intermittent
      pneumatic leg compression may have a role in osteoporosis prevention. It may
      provide a mean of inhibiting decline in femoral neck BMD, particularly in
      sedentary women.

PMID- 16099230
TI  - Management of early-stage cutaneous melanoma.

PMID- 16099232
TI  - The greater susceptibility of North Ronaldsay sheep compared with Cambridge sheep
      to copper-induced oxidative stress, mitochondrial damage and hepatic stellate
      cell activation.
AB  - Sheep of the semi-feral North Ronaldsay (copper-sensitive) and domesticated
      Cambridge (copper-tolerant) breeds were compared in respect of pathological
      changes and protein expression in the liver as a result of excessive dietary
      copper. Acute mitochondrial damage and hepatic stellate cell (HSC) activation
      with collagen synthesis occurred in response to moderate copper overload in North
      Ronaldsay but not in Cambridge sheep. Mitochondrial degradative changes occurred
      either as ballooning degeneration and rupture with subsequent autophagic
      degradation or as mitochondrial matrical condensation (pyknosis). In North
      Ronaldsay sheep prolonged exposure to copper produced mitochondrial hyperplasia
      and hypertrophy, and nuclear damage with necrosis. Cytosolic isocitrate
      dehydrogenase (IDH), an enzyme responsive to oxidative stress, was induced in the
      liver of Cambridge sheep receiving a Cu-supplemented diet but was undetectable in
      the non-supplemented control sheep. Conversely, IDH was detected at similar
      levels in both control and copper-supplemented North Ronaldsay sheep, indicating
      a lower threshold response, and an enhanced susceptibility, to oxidative stress.
      "Upregulation" of mitochondrial thioredoxin-dependent peroxidase reductase
      (antioxidant protein-1) in the hepatic cytosol of the North Ronaldsay (but not
      Cambridge) sheep affirmed the increased susceptibility of the mitochondria to Cu
      induced oxidative stress in this breed. Likewise the upregulation of cathepsin-D
      indicated increased lysosomal activity and HSC activation. The findings may be
      relevant to copper toxicosis in human infants.

PMID- 16099234
TI  - Translational medicine and the National Institutes of Health road map: steep
      grades and tortuous curves.

PMID- 16099235
TI  - Mycoplasma pneumoniae and central nervous system complications: a review.
AB  - Mycoplasma pneumoniae is a common cause of community-acquired pneumonia. Little
      is known about the extrapulmonary manifestations of this organism. Numerous
      central nervous system (CNS) manifestations have been described with M.
      pneumoniae. CNS involvement is probably the most common site of involvement in
      addition to the respiratory system. Up to 7% of patients hospitalized with M.
      pneumoniae may have CNS symptoms. Common CNS presentations include encephalitis,
      aseptic meningitis, polyradiculitis, cerebellar ataxia, and myelitis. The
      mechanism behind these CNS manifestations remains unclear. Direct invasion,
      neurotoxin production, or an immune-mediated mechanism has been proposed. Newer
      diagnostic techniques for the direct detection of the antigen and the
      microorganism are proving useful for the detection of extrapulmonary disease.
      This review comprehensively reviews the CNS complications that have been reported
      with M. pneumoniae.

PMID- 16099236
TI  - Evaluation of platelet function under high shear condition in the small-sized
      collagen bead column.
AB  - We previously reported that platelet retention rates as measured with collagen
      coated bead columns (the conventional column) reflect the processes of platelet
      adhesion and aggregation under low shear stress, and that this system could serve
      as an easy-to-use platelet aggregometry. With this column, platelet glycoprotein
      (GP) VI and GPIIb/IIIa, but not the GPIb-von Willebrand factor (VWF) interaction,
      play major roles in platelet activation. To develop a system that can better
      reflect the GPIb-VWF interaction under high shear stress, we designed a column
      containing small-sized beads (125-212 microm) coated with porcine collagen type
      I. As expected, the GPIb-VWF interaction played a crucial role in platelet
      retention rates at higher flow rates. Adenosine 5'-diphosphate, but not
      thromboxane A2, appears to support platelet activation in this system. The
      platelet retention rates among healthy individuals with the new columns are in
      the range wider than the conventional columns, and this diversity could be
      attributed to the broad range of the VWF antigen and/or its activity. It is
      suggested that this new column can serve as an easy-to-use method for evaluating
      the VWF antigen levels and its activity and for monitoring patients with
      thrombotic or bleeding disorders related to the VWF-GPIb interaction.

PMID- 16099237
TI  - Responses in extracellular and intracellular calcium and magnesium in
      aldosteronism.
AB  - We hypothesized the hypercalciuria and hypermagnesuria that accompany
      aldosteronism could be pharmacologically attenuated to prevent shifts in
      extracellular and intracellular levels of these divalent cations and the adverse
      outcomes associated with them. Accordingly, rats administered aldosterone/salt
      treatment (ALDOST) were cotreated with either hydrochlorothiazide (Hctz), to
      selectively reabsorb urinary Ca2+, or with Hctz plus spironolactone (Hctz+Spi),
      where Spi retards the excretion of these cations in both urine and feces. We
      monitored urinary excretion and responses in extracellular and intracellular Ca2+
      and Mg2+, together with indices of oxi/nitrosative stress in plasma and
      ventricular tissue. At 4 weeks ALDOST we found the following: (1) hypercalciuria
      was reduced by Hctz and normalized by Hctz+Spi, and this combination, unlike Hctz
      alone, also rescued hypermagnesuria; (2) the decrease in plasma-ionized [Ca2+]o
      was not seen with Hctz or Hctz+Spi, whereas Spi cotreatment protected against a
      decline in [Mg2+]o; (3) the Ca2+ loading of peripheral blood mononuclear cells
      and cardiac tissue was not seen with Hctz+Spi; and (4) the induction of
      oxi/nitrosative stress, expressed as reduced plasma alpha1-antiproteinase
      activity and activation of gp91(phox) subunit of NADPH oxidase in inflammatory
      cells invading intramural coronary arteries of the right and left ventricles,
      together with vascular fibrosis, was completely prevented by Spi cotreatment. In
      rats with aldosteronism, cotreatment with Hctz+Spi more effectively (vis-a-vis
      Hctz alone) protects against adverse iterations in extracellular and
      intracellular concentrations of Ca2+ and Mg2+, as well as the appearance of
      oxi/nitrosative stress to prevent the proinflammatory vascular phenotype.

PMID- 16099238
TI  - Tissue responses to thyroid hormone in a kindred with resistance to thyroid
      hormone harboring a commonly occurring mutation in the thyroid hormone receptor
      beta gene (P453T).
AB  - Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of reduced
      tissue responsiveness to thyroid hormone (TH) usually due to mutations in the TH
      receptor beta gene (TRbeta). We studied pituitary and peripheral tissue responses
      to graded doses of liothyronine (L-T3) in 5 affected members (2 children and 3
      adults) of a family with RTH due to the common TRbeta mutation P453T. Overall,
      the 5 subjects studied exhibited suppressed thyrotropin response to thyrotropin
      releasing hormone of 51% +/- 8%, 12.1% +/- 1.5%, and 6.3% +/- 3% of the 100%
      baseline on 50, 100, and 200 microg/dL L-T3, respectively. This degree of
      suppression was greater than that observed in subjects with RTH due to other
      TRbeta mutations, indicating less resistance. Compared with normal subjects,
      however, the family described here demonstrated less suppression by L-T3,
      compatible with their RTH, although of a mild magnitude. The 2 children with RTH
      demonstrated less L-T3-mediated suppression of prolactin and cholesterol than the
      adults. Patients often receive thyroid ablative therapy before the diagnosis of
      RTH and are left with variable degrees of hypothyroidism. Our results demonstrate
      that graded doses of L-T3 can be used to evaluate RTH patients, even under the
      condition of limited thyroid reserve, when results are compared with their
      baseline. We demonstrate that RTH patients can be evaluated either on or off
      thyroid hormone and still be distinguished from hypothyroid subjects without RTH.

PMID- 16099239
TI  - Analysis of epidermal entry in experimental cutaneous Bacillus anthracis
      infections in mice.
AB  - Cutaneous infection is the most common form of human anthrax, but little is known
      of Bacillus anthracis-epidermal interactions. To study the latter, we used
      experimental inoculations of B. anthracis Sterne spores onto mouse flank skin. In
      DBA/2 mice (a sensitive strain) 10(7) spores injected intradermally or applied
      under occlusive dressings to abraded skin produced ipsilateral inguinal edema and
      rapid death. Epicutaneous application to shaved-only skin produced edema and
      death in most animals, but at longer times. Mortality after inoculation onto
      abraded skin was less in C57BL/6 mice (a relatively resistant strain).
      Inoculations onto shaved-only skin immunized C57BL/6 mice, and they survived
      later intradermal spore injections. Histology revealed massive organism
      proliferation in remaining epidermis and hair follicles of inoculated abraded
      skin, but less growth in the dermis itself. Conversely, no foci could be located
      by microscopic examination after inoculation onto shaved-only skin. High-dose
      nonocclusive dressing inoculations onto unshaved skin in DBA/2 mice revealed
      small numbers of infective foci, all in hair follicles. These results suggest
      that epidermal damage may increase infection susceptibility to B. anthracis of
      hair follicle contents and remaining epidermal remnants; the findings also
      indicate that access may occur through hair follicles and the denuded dermis.

PMID- 16099243
TI  - Some collected principles of microneurosurgery: simple and fast, while preserving
      normal anatomy: a review.
AB  - Microneurosurgical techniques introduced by Prof Yasargil in the 1960s have
      increased the neurosurgeon's ability to operate in small and often very narrow
      and deep gaps. Microneurosurgical techniques-ensuring an almost bloodless field
      and mostly obviating need for transfusion-should be atraumatic and noninvasive to
      the already lesioned central nervous system tissues and structures. Instruments
      in microneurosurgery range from very short to very long and from sturdy to
      delicate, depending on the working depth, characteristics of tissues, and the
      microneurosurgical anatomy. However, to keep it simple and fast, and to
      appreciate normal anatomy, it is preferable to use only a limited array of
      instruments. Besides the use of instruments and the operating microscope,
      everything else in the neurosurgical arena should be optimized and professional,
      such as the positioning of the patient and the conduct of neuroanesthesia. This
      review of the very basics is distilled from the Helsinki and Kuopio neurosurgery
      practices in Finland and from the senior author's (JH) experience of close to
      10,000 operations, and this is to encourage young neurosurgeons of the world-most
      of them working with limited resources-to continue to improve their
      microneurosurgical skills to serve their patients best.

PMID- 16099244
TI  - Monoclonal antibody against E selectin attenuates subarachnoid hemorrhage-induced
      cerebral vasospasm.
AB  - BACKGROUND: Increasing evidence indicates that inflammatory responses are
      implicated in the pathogenesis of cerebral vasospasm after aneurysmal
      subarachnoid hemorrhage (SAH). However, the role of adhesion molecules in SAH
      induced vasospasm is less clear. This study was designed to examine the effect of
      a highly specific antibody, monoclonal anti-E-selectin antibody, on cerebral
      vasospasm in a new murine SAH model. METHODS: Experimental SAH was induced in
      C57Black/6J mice by injecting autogenous blood into the cisterna magna, and anti
      E-selectin antibody was administered intravenously immediately after SAH. All
      animals were killed by perfusion-fixation 24 hours after SAH. The diameters of
      anterior cerebral arteries (ACAs) were measured after arteries were cast with
      gelatin and india ink. Peripheral white blood cell count was also investigated.
      RESULTS: The average diameters of ACA were reduced by 22% and 25% in the SAH only
      and SAH plus vehicle groups, respectively, when compared with the healthy control
      group. After treatment with 12.5, 4, and 1 microg of anti-E-selectin antibody in
      mice subject to SAH, the average diameter of ACA was decreased by 9%, 10%, and
      22%, respectively, when compared with the healthy control group. The protective
      effects of anti-E-selectin antibody achieved statistical significance at doses of
      12.5 and 4 microg. Animals in the SAH only and SAH plus vehicle groups exhibited
      leukopenia. Administration of 12.5, 4, and 1 microg of anti-E-selectin antibody
      reduced leukopenia, and the total white blood cell count obtained in animals
      treated with 12.5- and 4-microg doses were significantly higher as compared with
      SAH animals. CONCLUSIONS: These findings provide the first evidence that anti-E
      selectin antibody was effective in prevention of SAH-induced vasospasm and imply
      a possible role of E selectin in the pathogenesis of vasospasm after SAH.

PMID- 16099246
TI  - Role of stereotactic radiosurgery as a primary treatment option in the management
      of newly diagnosed multiple (3-6) intracranial metastases.
AB  - OBJECTIVE: The objective of this study was to assess the role of stereotactic
      radiosurgery in the management of newly diagnosed multiple intracranial
      metastases from known primary cancer locations. METHODS: Fifty (29 women and 21
      men) patients received radiosurgery for newly diagnosed 3 or more metastatic
      brain tumors. Their mean age was 53 years. Lung cancer was the most common
      primary cancer (66%). RESULTS: Arrest in the growth of irradiated tumors was
      achieved in 41 (82%) patients. Eight patients (16%) required further intervention
      for tumors in other brain locations. Mean survival after diagnosis of brain
      disease was 12 months and the brain disease-controlled period was 19 months. The
      period of brain disease control prolonged (P=.03) with decreasing tumor volumes
      (<10 mL). Control of treated tumors positively affected survival after diagnosis
      of brain disease (P=.0001). CONCLUSION: Radiosurgery as an adjuvant improves
      survival in patients with cancer who have newly diagnosed multiple intracranial
      metastases by arresting the growth of tumors.

PMID- 16099247
TI  - The neuroprotective effects of z-DEVD.fmk, a caspase-3 inhibitor, on traumatic
      spinal cord injury in rats.
AB  - BACKGROUND: Apoptosis is one of the most important forms of cell death seen in a
      variety of physiological and pathological conditions, including traumatic
      injuries. This type of cell death occurs via mediators known as caspases.
      Previous studies have investigated the roles that apoptosis and different
      caspases play in the pathogenesis of secondary damage after spinal cord injury
      (SCI). The aim of this research was to assess the neuroprotective effect of z
      DEVD.fmk, a caspase-3 inhibitor, in a rat model of SCI. METHODS: Forty-five
      Wistar albino rats were studied in 3 groups of 15 animals: sham-operated control
      animals (group 1); trauma-only control animals (group 2); and rats subjected to
      trauma + z-DEVD.fmk treatment (group 3). Spinal cord injury was produced at the
      thoracic level using the weight-drop technique. Responses to injury and the
      efficacy of z-DEVD.fmk were assessed by light microscopy and terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      staining in cord tissues collected at 4 and 24 hours posttrauma. Five rats from
      each group were used to assess functional recovery at 7 days after SCI. The
      functional evaluations were done using the inclined-plane technique and a
      modified Tarlov motor grading scale. RESULTS: At 4 hours postinjury, the mean
      apoptotic index in groups 1, 2, and 3 was 0, 33.01+/-6.62, and 16.40+/-4.91,
      respectively. The group 3 count was significantly lower than the group 2 count
      (P<.01). At 24 hours postinjury, light microscopic examination of group 2 tissues
      showed widespread hemorrhage, necrosis, polymorphonuclear leukocyte infiltration,
      and vascular thrombi. The group 3 tissues showed similar features. The prominent
      findings in group 2 were hemorrhage and necrosis, whereas the prominent findings
      in group 3 were focal hemorrhage and leukocyte infiltration. The mean inclined
      plane angles in groups 1, 2, and 3 were 64.5 degrees+/-1.0 degrees, 41.5
      degrees+/-1.3 degrees, and 47 degrees+/-2.0 degrees, respectively. Motor scale
      results in all groups showed a similar trend. CONCLUSION: Local application of z
      DEVD.fmk after SCI in rats reduces secondary tissue injury and helps preserve
      motor function. These effects can be explained by inhibition of apoptotic death
      in all cell types in the spinal cord.

PMID- 16099249
TI  - Poor surgical technique in cervical plating leading to vertebral artery injury
      and brain stem infarction--case report.
AB  - BACKGROUND: Lateral mass plating is a safe fixating system for lower cervical
      fractures. Brain stem infarction after cervical lateral mass screw plating has
      not been reported in previous literature. We report a case of poor surgical
      technique leading to vertebral artery injury and brain stem infarction after
      cervical lateral mass plating. CASE DESCRIPTION: A 41-year-old male patient was
      transferred to our hospital because of hemiparesis and dysarthria immediately
      after lateral mass plating for fracture and dislocation of the fifth and sixth
      cervical vertebrae. Brain magnetic resonance imaging showed infarction of the
      left posterior inferior cerebellar artery territory, and the vertebral artery
      angiography showed complete occlusion of the left vertebral artery. The cervical
      computed tomography revealed a left screw of the fifth and sixth cervical
      vertebrae penetrating the central portion of the transverse foramen. The patient
      was managed with anticoagulant and supportive therapy only, with subsequent
      improvement of hemiparesis and dysarthria. CONCLUSIONS: Poor surgical technique
      of lateral mass plating in the cervical spine could lead to vertebral artery
      injury and even brain stem infarction. Postoperative brain infarction in cervical
      fusion could be a complication of the usually safe lateral mass plating of the
      cervical spine.

PMID- 16099250
TI  - Recurrent lumbar disc herniation after discectomy: outcome of repeat discectomy.
AB  - BACKGROUND: Recurrent disc herniation after discectomy is relatively lacking in
      specific studies and is usually reviewed along with other causes of failed disc
      surgery. The purpose of the current study was to address the outcome in the
      patients who had recurrent disc herniation treated with repeat discectomy and to
      identify the factors that may influence the outcome. METHODS: Thirty-nine
      patients who underwent repeat discectomy for recurrent lumbar disc herniation
      were retrospectively analyzed. Of these patients, 27 had recurrent disc
      herniation at the L4 to L5 level, 11 at the L5 to S1, and 1 at the L3 to L4. They
      almost had the typical presentation of sciatica. The time from prior discectomy
      to that of recurrence ranged 6 months to 17 years (average, 5 years and 4
      months). The Japanese Orthopaedic Association (JOA) score averaged 12 (range, -3
      to 18). All patients had a follow-up evaluation at 1 and 15 years (average, 7
      years and 8 months) after surgery. RESULTS: Their JOA score increased to 12 to 29
      (average, 24), with the recovery rate of 29% to 100% (average, 72%). Twenty-nine
      patients returned to their previous work status or normal daily activity, 7 had
      significant improvement, and 3 needed analgesic drugs although they had pain
      relief to different degrees. CONCLUSIONS: The outcomes of repeat discectomy for
      recurrent disc herniation were satisfactory. No factors such as age, sex,
      traumatic events, times of prior surgery, level of herniation, side of
      recurrence, pain-free interval, duration of recurrence symptoms, walking
      capacity, the preoperative JOA score, associated spinal stenosis, procedures of
      revision surgery, and dural tear were found to be of predictive value for a
      prognosis of revision surgery for recurrent disc herniation (P>.05).

PMID- 16099252
TI  - Smooth dissection of ligamentum flavum for lumbar microdiscectomy. Preliminary
      report of this personal technique.
AB  - A newly designed technique for preservation of the ligamentum flavum (LF) during
      the lumbar discectomy is presented. This technique allows the evacuation of the
      lumbar herniated disk, without removal or laminar disinsertion of the LF. This
      ligament is smoothly dissected longitudinally in its more lateral portion,
      obtaining, after discectomy, the contact of the 2 margins with restoration of its
      functional integrity. Forty-five patients were operated on with this technique.
      We feel that this technique could offer advantages in reduction of epidural
      fibrosis and of decreased risk of dural injury, and is helpful to the surgeon in
      the case of recurrence of discal herniation.

PMID- 16099255
TI  - Chiari type I malformations in adults: a morphometric analysis of the posterior
      cranial fossa.
AB  - OBJECTIVE: Chiari type I malformation (CMI) is a congenital disorder
      characterized by caudal displacement of the cerebellar tonsils through the
      foramen magnum into the spinal canal. Recent studies suggest that overcrowding in
      the posterior cranial fossa (PCF) because of underdeveloped bony structures in
      the intrauterine life is the main cause of this malformation. For this reason,
      the authors want to contribute to the current literature, which focuses on bone
      abnormalities in the PCF in patients with CMIs. METHODS: We examined a
      retrospective cohort of 60 adult patients with CMIs, and multiple measurements
      were made on magnetic resonance imaging. The results were compared to 30 healthy
      adult control subjects. Mann-Whitney U test was used as a statistical method.
      RESULTS: All measurements except mean anteroposterior diameter of the foramen
      magnum were reduced in patients compared to control. An increase in the
      anteroposterior mid-sagittal distance of the foramen magnum in patients reached
      statistically significant difference compared to control. All patients had
      tonsillar herniation at least 5 mm below the plane of the foramen magnum. Chiari
      type I malformation in this study was associated with syringomyelia in 46
      patients. CONCLUSION: This study with a limited number of patients suggests that
      the bony components of the PCF are not developed fully, supporting the current
      concept that CMI is a disorder of the para-axial mesoderm.

PMID- 16099256
TI  - Contralateral meningeal artery supply of paramedian meningiomas.
AB  - BACKGROUND: When resecting at falcine or parasagittal portion of paramedian
      meningiomas, intraoperative hemostasis often is difficult despite effective
      management of ipsilateral meningeal arteries. We attribute such difficulties to
      meningeal artery blood supply from the contralateral side. We retrospectively
      studied feeding arteries from both sides in case of paramedian meningioma in
      terms of patient and tumor characteristics. METHODS: Forty-three patients with
      paramedian meningiomas underwent selective internal and external carotid
      angiography. We investigated how contralateral meningeal arterial feeders related
      to patient profiles and imaging, histopathologic, and immunohistochemical
      findings. RESULTS: Contralateral meningeal supply existed for 14 of 25 falcine
      meningiomas and 6 of 18 parasagittal meningiomas. Patients with contralateral
      feeders were 8.5 years younger than the others (P=.027) and were more likely to
      have larger tumors (P=.028). These were histopathologically malignant (P=.048),
      while showing more proliferation followed by monoclonal antibody against the Ki
      67 antigen index (P=.012) and angiogenetic potential associated with vascular
      endothelial growth factor expression (P=.0085). CONCLUSIONS: Contralateral
      meningeal supply may reflect strong angiogenetic recruitment from rapid tumor
      growth followed by high expression of vascular endothelial growth factor. This
      angiographical feature may predict the aggressive growth of paramedian
      meningiomas.

PMID- 16099258
TI  - Peroneal nerve compression resulting from fibular head osteophyte-like lesions.
AB  - BACKGROUND: The anatomical relationship of the fibular head with the fibular
      nerve is a critical point in regard to injuries of peripheral nerves in the lower
      extremities. In this location, the peroneal nerve may be injured due to several
      mechanisms, and osteophyte-like lesions can be considered as a differential
      diagnosis. METHODS: The suitable literature concerning this association is
      reviewed and a case is presented. A 15-year-old adolescent boy presented with
      right peroneal nerve palsy on admission. The radiological examinations (computed
      tomography and magnetic resonance imaging) demonstrated an osteophytic lesion in
      the head of the right fibula. The patient underwent surgical decompression of the
      nerve and resection of the lesion. Postoperatively, there was a complete recovery
      of the deficits. CONCLUSIONS: The association of osteophyte-like bone changes and
      peroneal nerve palsy is rare. The differential diagnoses of these lesions include
      cartilaginous exostoses and osteochondromas, which may be related to hereditary
      multiple exostoses syndrome. The timing of the treatment plays an important role
      in the neurological recovery.

PMID- 16099259
TI  - Evaluation of invasiveness and efficacy of 2 different keyhole approaches to
      large basal ganglia hematomas.
AB  - BACKGROUND: The aim of this study was to evaluate the invasiveness and efficacy
      of 2 different keyhole approaches to large basal ganglia hematomas (LBGHs).
      METHODS: The invasiveness and efficacy of the temporal (15 cases) and the frontal
      (15 cases) microsurgical keyhole approach were retrospectively evaluated in 30
      early-operated patients with LBGH, using recorded neuronavigation data.
      Invasiveness was assessed calculating the angles of brain retraction and the
      volume of brain exposed to surgery. Reduced invasiveness was related to a fall of
      these values. Efficacy was evaluated by comparing the volume of microscopically
      visualized clot and the largest hemorrhage diameter exposed with the 2 different
      keyhole approaches. Increased efficacy was related to a rise in these parameters.
      All estimations were correlated to the volume of residual clot detected on
      postoperative computed tomography scan. RESULTS: The comparison between both
      approaches revealed a significant reduction of invasiveness (smaller angles of
      brain retraction [P<.001] and reduced brain exposition [P<.001]), as well as a
      raised efficacy (increased volume of visualized clot [P<.001] and largest
      hemorrhage diameter exposed to surgery [P<.001]) for frontally approached LBGH.
      These patients showed less postoperative residual hematomas (P<.05). Residual
      clots were correlated to the evaluated brain retraction (P<.001) and volume of
      brain (P<.001), as well as volume of clot surgically exposed (P<.05). CONCLUSION:
      We conclude that the frontal approach to LBGH leads to less invasiveness and
      higher efficacy as evaluated by using neuronavigation data. This approach shows a
      reduced number of patients with residual postoperative clots.

PMID- 16099260
TI  - A ruptured middle cerebral artery aneurysm originating from the site of
      anastomosis 20 years after extracranial-intracranial bypass for moyamoya disease:
      case report.
AB  - BACKGROUND: Direct revascularization through a superficial temporal artery-middle
      cerebral artery (STA-MCA) bypass is often performed to prevent ischemic or
      hemorrhagic attack in patients with moyamoya disease. This is the first reported
      case of aneurysm formation and rupture due to an STA-MCA bypass in a patient with
      moyamoya disease. CASE DESCRIPTION: A 52-year-old man who had undergone bilateral
      STA-MCA bypass for caudate hemorrhage due to moyamoya disease 20 years previously
      suffered from sudden-onset unconsciousness. Computed tomography revealed a
      massive intracerebral hematoma (ICH) in the left frontoparietal region.
      Angiography showed good patency of the anastomoses and stage IV moyamoya disease.
      However, no other abnormality was found. Emergency evacuation of the hematoma was
      performed. The patient's postoperative course was uneventful, but consciousness
      disturbance of sudden onset occurred 1 month later. Computed tomography showed a
      hematoma in the lateral ventricle and acute hydrocephalus. Repeat angiography
      revealed an aneurysm on the left side of the anastomosis. Bilateral ventricle
      drainage tubes were inserted, and the aneurysm was clipped. A
      ventriculoperitoneal shunt was later performed. CONCLUSION: In patients with
      moyamoya disease who have undergone extracranial-intracranial bypass surgery,
      progressive hemodynamic stress may cause the formation of de novo aneurysms after
      a postoperative period of several decades. Imaging examinations should therefore
      be performed periodically for follow-up, and a de novo aneurysm should be
      suspected in a patient who has an unusual ICH.

PMID- 16099263
TI  - Intravascular papillary endothelial hyperplasia at the superior orbital fissure:
      report of a case successfully treated with gamma knife radiosurgery.
AB  - BACKGROUND: An intracranial lesion of intravascular papillary endothelial
      hyperplasia (IPEH) is extremely rare and often difficult to resect completely. We
      describe a case in which a lesion at the superior orbital fissure was
      successfully treated by postoperative radiosurgery. CASE DESCRIPTION: A 41-year
      old woman presented with progressive left abducens nerve paresis and left facial
      sensory disturbance over a 1-year period. Radiological examination demonstrated a
      left middle fossa tumor involved in the cavernous sinus. About a half removal of
      the tumor was performed. The pathological diagnosis was IPEH. The residual tumor
      was treated with gamma knife radiosurgery. CONCLUSION: Gamma knife radiosurgery
      was effective to reduce the residual tumor in the present case. During a follow
      up period of 2 years, the lesion has not recurred. This report suggests that
      additional gamma knife radiosurgery after incomplete resection of the lesion
      could be an alternative therapeutic modality.

PMID- 16099264
TI  - Ventricular catheter tack-down suture: technical note.
AB  - Tubing migration accounts for a significant number of shunt complications. In an
      attempt to reduce the likelihood of disconnection and tubing migration, we have
      developed a technique to rigidly fix the proximal catheter to the skull. The
      method involves the placement of a small twist drill hole adjacent to the
      catheter burr hole through which a suture is passed. The suture is then used to
      rigidly bind the proximal shunt tubing and valve to the skull. This approach
      provides an efficient and effective means for reducing complications related to
      shunt tubing migration.

PMID- 16099265
TI  - Application of multichannel near-infrared spectroscopic topography to
      physiological monitoring of the cortex during cortical mapping: technical case
      report.
AB  - BACKGROUND: Cortical stimulation via a subdural grid electrode (SGE) is one of
      the most reliable methods for identifying eloquent areas before surgery. However,
      the physiological conditions of the cortex during stimulation cannot be monitored
      electrophysiologically because of electrical artifacts. In the present case, we
      tested whether or not multichannel near-infrared spectroscopy (NIRS) topography,
      a noninvasive optical imaging technique, is applicable for monitoring the
      physiological conditions of the stimulated cortex. CASE DESCRIPTION: The patient
      (a 27-year-old right-handed man) suffered from glioma in the left frontal lobe.
      For preoperative cortical mapping, SGEs were implanted over the left motor cortex
      before tumor resection. Employing NIRS topography, we undertook 2 dimensional
      imaging of the changes in oxyhemoglobin (Oxy-Hb) and deoxyhemoglobin (Deoxy-Hb)
      concentration during electrical stimulation. Five-hertz stimulation with 5 mA at
      the left-hand area produced a localized increase in Oxy-Hb and a decrease in
      Deoxy-Hb, associated with slight twitching of the right hand. In contrast, 50-Hz
      stimulation produced significant increases in both Oxy-Hb and Deoxy-Hb at the
      stimulation site, and the area with such cerebral blood oxygenation (CBO) changes
      propagated beyond the hand area associated with prominent muscle contractions of
      the right upper extremity, suggesting that 50-Hz stimulation caused epileptic
      discharge. CONCLUSION: Near-infrared spectroscopy topography may represent a
      useful tool for imaging the degree and extent of the physiological effects of
      electrical stimulation on the cortex, and permits safe and accurate cortical
      mapping.

PMID- 16099266
TI  - Enhancing medical care in the United States via health savings accounts.

PMID- 16099268
TI  - Spinal epidural abscess: clinical presentation, management and outcome (Curry WT,
      Hoh BL, Hanjani SA, et al. Surg Neurol 2005;63:364-71).

PMID- 16099269
TI  - Colorectal cancer: not an embarrassing problem.

PMID- 16099270
TI  - The Global Fund plans an image makeover.

PMID- 16099271
TI  - Taking a closer look at drug advertisements.

PMID- 16099272
TI  - Valproic acid: a potential role in treating latent HIV infection.

PMID- 16099273
TI  - Postoperative radiotherapy for prostate cancer.

PMID- 16099274
TI  - Immunohistopathology to guide multiple sclerosis treatment.

PMID- 16099275
TI  - Vegetables, fruit, and cancer.

PMID- 16099276
TI  - Risk stratification in Brugada syndrome.

PMID- 16099277
TI  - Microbial challenge studies--a challenge worth accepting.

PMID- 16099278
TI  - H5N1 influenza pandemic: contingency plans.

PMID- 16099279
TI  - Detlev Ganten: taking on the challenges at Berlin's Charite.

PMID- 16099280
TI  - Prevention of low-trauma fractures in older people.

PMID- 16099282
TI  - Prevention of low-trauma fractures in older people.

PMID- 16099283
TI  - Depression in elderly people.

PMID- 16099284
TI  - Prevention of low-trauma fractures in older people.

PMID- 16099286
TI  - Intermittent preventive malaria treatment in Tanzanian infants.

PMID- 16099287
TI  - Palliative care in sub-Saharan Africa.

PMID- 16099288
TI  - Eye injuries in children: a new household risk.

PMID- 16099289
TI  - The trouble with likelihood ratios.

PMID- 16099291
TI  - Capillary leak syndrome in children with C4A-deficiency undergoing cardiac
      surgery with cardiopulmonary bypass: a double-blind, randomised controlled study.
AB  - BACKGROUND: Capillary leak syndrome is a life-threatening complication after
      cardiopulmonary bypass (CPB), with an incidence of about 4-37% in children
      worldwide. On the basis of previous results, we undertook a randomised controlled
      study to investigate the priming with plasma rich in the C4A isotype of
      complement component 4 on the incidence of capillary leak syndrome in children
      with C4A deficiency. METHODS: In a hospital in Wuhan, China, we randomly assigned
      116 neonates, infants, and children lacking complement component C4A to receive
      C4A-free or C4A-rich plasma priming (n=58 each, 20 mL/kg). The primary outcome
      was capillary leak syndrome, identified as an increased transvascular escape rate
      of Evans blue dye from plasma. Concentrations of activated complement components
      C4 and C3, inflammatory mediators interleukin 6, interleukin 8, tumour necrosis
      factor (TNF) alpha, plasma protein, and PaO2/F(I)O2 ratios (ratio of the partial
      arterial pressure of oxygen to the fractional concentration of oxygen in inspired
      air) were measured before and 4 h after CPB. Analysis was by intention to treat.
      FINDINGS: Three (5%) patients given C4A-rich plasma priming had capillary leak
      syndrome compared with 56 (97%) given C4A-free plasma (p<0.0001). At 4 h after
      CPB, activated C4, interleukin 6, interleukin 8, and TNFalpha concentrations were
      higher, whereas PaO2/F(I)O2 ratios and plasma protein concentrations were
      significantly lower in the C4A-free group than changes in the C4A-rich group.
      Activated C3 rose equally in both groups. Activated C4 significantly correlated
      with interleukin 6, interleukin 8, and TNFalpha concentrations; PaO2/F(I)O2
      ratios; and the escape rate of Evans blue dye at 4 h after CPB. Two patients in
      the C4A-free group died of respiratory and renal failure on day 3 after CPB.
      INTERPRETATION: In paediatric patients with C4A deficiency, C4A-rich plasma
      priming reduces the incidence of CPB-related capillary leak syndrome by blocking
      the activated C4 increase and attenuating the systemic inflammatory response
      after CPB.

PMID- 16099290
TI  - Depletion of latent HIV-1 infection in vivo: a proof-of-concept study.
AB  - BACKGROUND: Persistent infection in resting CD4+ T cells prevents eradication of
      HIV-1. Since the chromatin remodeling enzyme histone deacetylase 1 (HDAC1)
      maintains latency of integrated HIV, we tested the ability of the HDAC inhibitor
      valproic acid to deplete persistent, latent infection in resting CD4+ T cells.
      PROCEDURES: We did a proof-of-concept study in four volunteers infected with HIV
      and on highly-active antiretroviral therapy (HAART). After intensifying the
      effect of HAART with subcutaneous enfuvirtide 90 mug twice daily for 4-6 weeks to
      prevent the spread of HIV, we added oral valproic acid 500-750 mg twice daily to
      their treatment regimen for 3 months. We quantified latent infection of resting
      CD4+ T cells before and after augmented treatment by limiting-dilution culture of
      resting CD4+ T cells after ex-vivo activation. FINDINGS: The frequency of resting
      cell infection was stable before addition of enfuvirtide and valproic acid, but
      declined thereafter. This decline was significant in three of four patients (mean
      reduction 75%, range 68% to >84%). Patients had slight reactions to enfuvirtide
      at the injection site, but otherwise tolerated treatment well. INTERPRETATION:
      Combination therapy with an HDAC inhibitor and intensified HAART safely
      accelerates clearance of HIV from resting CD4+ T cells in vivo, suggesting a new
      and practical approach to eliminate HIV infection in this persistent reservoir.
      This finding, though not definitive, suggests that new approaches will allow the
      cure of HIV in the future.

PMID- 16099292
TI  - Roflumilast--an oral anti-inflammatory treatment for chronic obstructive
      pulmonary disease: a randomised controlled trial.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by
      progressive airflow limitation associated with chronic inflammation. There are
      few treatment options for the disease. This study assessed the efficacy and
      safety of roflumilast, a phosphodiesterase-4 inhibitor, in patients with moderate
      to severe COPD. METHODS: This phase III, multicentre, double-blind, randomised,
      placebo-controlled study was undertaken in an outpatient setting. 1411 patients
      with COPD were randomly assigned roflumilast 250 microg (n=576), roflumilast 500
      microg (n=555), or placebo (n=280) given orally once daily for 24 weeks. Primary
      outcomes were postbronchodilator FEV1 and health-related quality of life.
      Secondary outcomes included other lung function parameters and COPD
      exacerbations. Analyses were by intention to treat. FINDINGS: 1157 (82%) patients
      completed the study; 32 (11%) withdrew from the placebo group, 100 (17%) from the
      roflumilast 250 microg group, and 124 (22%) from the roflumilast 500 microg
      group. Postbronchodilator FEV1 at the end of treatment significantly improved
      with roflumilast 250 microg (by 74 mL [SD 18]) and roflumilast 500 microg (by 97
      mL [18]) compared with placebo (p<0.0001). Improvement in health-related quality
      of life was greater with roflumilast 250 microg (-3.4 units [0.6]) and
      roflumilast 500 microg (-3.5 units [0.6]) than with placebo (-1.8 units [0.8]),
      although the differences between treatment groups were not significant. The mean
      numbers of exacerbations per patient were 1.13 (2.37), 1.03 (2.33), and 0.75
      (1.89) with placebo, roflumilast 250 microg, and roflumilast 500 microg,
      respectively. Most adverse events were mild to moderate in intensity and resolved
      during the study. INTERPRETATION: Roflumilast is a promising candidate for anti
      inflammatory COPD treatment because it improved lung function and reduced
      exacerbations compared with placebo. Long-term studies are needed to fully assess
      the effect on health-related quality of life.

PMID- 16099293
TI  - Postoperative radiotherapy after radical prostatectomy: a randomised controlled
      trial (EORTC trial 22911).
AB  - BACKGROUND: Local failure after prostatectomy can arise in patients with cancer
      extending beyond the capsule. We did a randomised controlled trial to compare
      radical prostatectomy followed by immediate external irradiation with
      prostatectomy alone for patients with positive surgical margin or pT3 prostate
      cancer. METHODS: After undergoing radical retropubic prostatectomy, 503 patients
      were randomly assigned to a wait-and-see policy, and 502 to immediate
      postoperative radiotherapy (60 Gy conventional irradiation delivered over 6
      weeks). Eligible patients had pN0M0 tumours and one or more pathological risk
      factors: capsule perforation, positive surgical margins, invasion of seminal
      vesicles. Our revised primary endpoint was biochemical progression-free survival.
      Analysis was by intention to treat. FINDINGS: The median age was 65 years (IQR 61
      69). After a median follow-up of 5 years, biochemical progression-free survival
      was significantly improved in the irradiated group (74.0%, 98% CI 68.7-79.3 vs
      52.6%, 46.6-58.5; p<0.0001). Clinical progression-free survival was also
      significantly improved (p=0.0009). The cumulative rate of locoregional failure
      was significantly lower in the irradiated group (p<0.0001). Grade 2 or 3 late
      effects were significantly more frequent in the postoperative irradiation group
      (p=0.0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5
      year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative
      irradiation group (p=0.0726). INTERPRETATION: Immediate external irradiation
      after radical prostatectomy improves biochemical progression-free survival and
      local control in patients with positive surgical margins or pT3 prostate cancer
      who are at high risk of progression. Further follow-up is needed to assess the
      effect on overall survival.

PMID- 16099294
TI  - Relation between humoral pathological changes in multiple sclerosis and response
      to therapeutic plasma exchange.
AB  - Early, active multiple sclerosis lesions show four immunopathological patterns of
      demyelination. Although these patterns differ between patients, multiple active
      lesions from a given patient have an identical pattern, which suggests pathogenic
      heterogeneity. Therapeutic plasma exchange (TPE) has been successfully used to
      treat fulminant demyelinating attacks unresponsive to steroids. We postulated
      that patients with pattern II would be more likely to improve after TPE than
      those with other patterns since pattern II lesions are distinguished by prominent
      immunoglobulin deposition and complement activation. We retrospectively studied
      19 patients treated with TPE for an attack of fulminant CNS inflammatory
      demyelinating disease. All patients with pattern II (n=10), but none with pattern
      I (n=3) or pattern III (n=6), achieved moderate to substantial functional
      neurological improvement after TPE (p<0.0001). Patients with multiple sclerosis
      with pattern II pathology are more likely to respond favourably to TPE than are
      patients with patterns I or III.

PMID- 16099295
TI  - Ectopic pregnancy.
AB  - Ectopic pregnancy is an important cause of morbidity and mortality worldwide. Use
      of transvaginal ultrasonography and quantitative measurement of the beta subunit
      of human chorionic gonadotropin (beta-hCG) has led to a reduction in the need for
      diagnostic laparoscopy. Furthermore, with earlier diagnosis, medical therapy with
      methotrexate can be offered and surgery avoided in some women, though the best
      regimen remains unclear. In the surgical management of ectopic pregnancy, the
      benefits of salpingectomy over salpingostomy are uncertain. Although there have
      been advances in the management of ectopic pregnancy there are still questions to
      be answered.

PMID- 16099296
TI  - Stem cells.
AB  - Stem cells derived from adult and embryonic sources have great therapeutic
      potential, but much research is still needed before their clinical use becomes
      commonplace. There is debate about whether adult stem cells can be used instead
      of those derived from embryos. Rationalisation is needed but can be exercised
      only once the various cells have been carefully compared and contrasted under
      appropriate experimental conditions. Some characteristics that might help resolve
      the issue of cell source can already be applied to the debate. Accessibility is
      important; some adult cells, such as neural stem cells, are difficult to obtain,
      at least from living donors. Other factors include the frequency and abundance of
      adult stem cells and their numbers and potency, which might decline with age or
      be affected by disease. For embryonic stem cells, ethical concerns have been
      raised, and the proposed practice of therapeutic cloning tends to be
      misrepresented in the lay media. For both adult and embryonic stem cells,
      stability, potential to transmit harmful pathogens or genetic mutations, and risk
      of forming unwanted tissues or even teratocarcinomas have yet to be fully
      assessed.

PMID- 16099297
TI  - The case for a new Global Fund for maternal, neonatal, and child survival.

PMID- 16099298
TI  - A tumour masquerade.

PMID- 16099299
TI  - Area-specific effects of brain-derived neurotrophic factor (BDNF) genetic
      ablation on various neuronal subtypes of the mouse brain.
AB  - The effects of brain-derived neurotrophic factor (BDNF) on the development of
      presynaptic terminals and of neuronal subtypes in various brain areas were
      studied in BDNF-knockout (BDNF-/-) mice at postnatal days 15-17. Western analysis
      revealed no changes in the overall amount of a variety of synaptic proteins in
      BDNF-/- mice as compared to wild type mice. In addition, the complex between the
      vesicular proteins, synaptophysin and synaptobrevin, as well as their respective
      homodimers were unaltered. Moreover, no changes in the density of neurons were
      found in, e.g., the CA3 region of the hippocampus and the nucleus nervi facialis
      of BDNF-/- mice. However, cholinergic cells were reduced by 20% in the medial
      septum of BDNF-/- mice associated with a decrease in the activity of choline
      acetyltransferase and protein levels of nerve growth factor in the hippocampus by
      16% and 44%, respectively. In the striatum, however, the total number of
      cholinergic cells were comparable in both groups, although the activity of
      choline acetyltransferase was decreased by 46%. In GABAergic interneurons, the
      expression of neuropeptides in various brain areas was differentially affected by
      BDNF deletion as revealed by immunohistochemistry. In the hippocampus and cortex
      of BDNF-/- mice, the density of neuropeptide Y-, somatostatin-, and parvalbumin
      immunoreactive cells was drastically reduced, whereas the density of calretinin
      positive cells was increased. The extent of these changes in neuropeptide
      containing cells varied among hippocampal subregions. In the striatum, only the
      density of parvalbumin-immunoreactive cells was decreased by approximately 45%.
      In conclusion, BDNF deficiency is accompanied by a differential dysregulation in
      the expression of neuropeptides and calcium-binding proteins in otherwise intact
      GABAergic and glutamatergic neurons in a region-specific manner.

PMID- 16099300
TI  - Plasminogen activators contribute to age-dependent impairment of NMDA
      cerebrovasodilation after brain injury.
AB  - Previous studies have observed that fluid percussion brain injury (FPI) impaired
      NMDA induced pial artery dilation in an age-dependent manner. This study was
      designed to investigate the contribution of plasminogen activators to impaired
      NMDA dilation after FPI in newborn and juvenile pigs equipped with a closed
      cranial window. In the newborn pig, NMDA (10(-8), 10(-6) M) induced pial artery
      dilation was reversed to vasoconstriction following FPI, but pretreatment with
      the plasminogen activator inhibitor PAI-1 derived hexapeptide (EEIIMD) (10(-7) M)
      prevented post injury vasoconstriction (9 +/- 1 and 16 +/- 1, vs. -6 +/- 2 and-11
      +/- 3, vs. 5 +/- 1 and 9 +/- 1% for responses to NMDA 10(-8), 10(-6) M prior to
      FPI, after FPI, and after FPI in EEIIMD pretreated animals, respectively). In
      contrast, in the juvenile pig, NMDA dilation was only attenuated following FPI
      and EEIIMD pretreatment partially prevented such inhibition (9 +/- 1 and 16 +/- 1
      vs. 2 +/- 1 and 4 +/- 1 vs. 5 +/- 1 and 7 +/- 1% for responses to NMDA prior to
      FPI, after FPI, and after FPI in EEIIMD pretreated animals, respectively).
      Additionally, EEIIMD blunted age-dependent pial artery vasoconstriction following
      FPI. EEIIMD blocked dilation to the plasminogen activator agonists uPA and tPA
      while responses to SNP and papaverine were unchanged. Pretreatment with suPAR,
      which blocked dilation to uPA, elicited effects on pial artery diameter and NMDA
      vascular activity post FPI similar to that observed with EEIIMD. These data show
      that EEIIMD and suPAR partially prevented FPI induced alterations in NMDA
      dilation and reductions in pial artery diameter. EEIIMD and suPAR are efficacious
      and selective inhibitors of plasminogen activator induced dilation. These data
      suggest that plasminogen activators contribute to age-dependent impairment of
      NMDA induced dilation following FPI.

PMID- 16099301
TI  - Changes in expression of P2X purinoceptors in rat cerebellum during postnatal
      development.
AB  - Changes in expression of P2X receptors (P2X1-7) during postnatal development of
      the rat cerebellum are described. At P3, immunoreactivity (ir) to all the P2X
      receptors, except for P2X3 receptors, was found in Purkinje cells and deep
      cerebellar nuclei, P2X5-ir being most prominent. Granular and microglial cells
      were labeled for P2X5 (weakly) and P2X4 receptors, respectively. At P7,
      expression of all the P2X receptors (with the exception of P2X3) was up
      regulated, P2X5 and P2X6 receptors being most prominent. Scattered P2X receptor
      ir in unipolar brush cells in the granular cell layer and P2X1- and P2X7-ir of
      microglial cells was also present. At P14, the dendritic trees of Purkinje cells
      were intensely labeled by P2X1-7 receptor antibodies, except for P2X3, while
      P2X1, P2X4 and P2X7 receptor immunostaining in microglial cells and P2X5 receptor
      immunostaining in granular cells was up-regulated. At P21, expression of all P2X
      receptors (except P2X3) was down-regulated in the Purkinje cells and deep
      cerebellar nuclei; P2X1, P2X4 and P2X7 receptors-ir was present in microglial
      cells. In contrast, expression of P2X5-ir in granular cells was up-regulated. At
      P60, expression levels of all the P2X receptors (except P2X3) were similar with
      those at P21. In double-labeling experiments, almost all the P2X-ir Purkinje
      cells were immunoreactive for calbindin-D28k, while 60-80% of P2X-ir cells in the
      granular cell layer were immunoreactive for calretinin. The possible short- and
      long-term functional significance of the changes in expression of P2X receptors
      during postnatal development is discussed.

PMID- 16099302
TI  - Lack of experience-mediated differences in the immunohistochemical expression of
      blood-brain barrier markers (EBA and GluT-1) during the postnatal development of
      the rat visual cortex.
AB  - The development of the cortical vascular tree depends on functional development.
      External inputs are an essential requirement in the modeling of the visual
      cortex, mainly during the critical period, when congruous blood supply is needed.
      The blood brain barrier (BBB) function regulates the passage of substances
      between the blood and the brain parenchyma, which is one of the main differential
      features of central nervous system (CNS) microvessels. The endothelial barrier
      antigen (EBA) has been reported as a specific marker for the BBB physiological
      function in rats. We studied the postnatal development of EBA expression in the
      visual cortex of rats reared under opposite paradigms of visual experience, e.g.,
      standard laboratory conditions, dark rearing, and enriched environment at 14, 21,
      28, 35, 42, 49, 56, and 63 days postnatal (dpn). Parallel sections were
      immunohistochemically processed for endothelial barrier antigen (EBA) and glucose
      transporter-1 (GluT-1). Total vasculature was quantified by Lycopersicon
      esculentum (LEA) lectin histochemistry. No differences in EBA expression were
      found between groups, although quantitative differences were recorded paralleling
      differences in vascular density. Paradoxically, there was no expression in
      certain cortical vessels which were GluT-1 immunopositive and positivity was
      consistent in non-barrier areas such as the pineal gland. These findings were
      completely independent of age or experimental conditions. Therefore, the role of
      the EBA antigen in the BBB remains unclear: it has been undeniably linked to
      vascular permeability, but its presence in non-barrier vessels suggests another
      vascular function. Although visual experience modifies vascular density in the
      visual cortex, it has not been shown to have an influence on the maturation of
      the BBB function.

PMID- 16099303
TI  - Neonatal depletion of cortical dopamine: effects on dopamine turnover and motor
      behavior in juvenile and adult rats.
AB  - Abnormal development of mesoprefrontal dopamine (DA) neurons may contribute to
      the pathophysiology of schizophrenia. Consistent with this hypothesis, DA nerve
      terminal density is decreased in the cortex of schizophrenic subjects [M. Akil,
      J.N. Pierri, R.E. Whitehead, C.L. Edgar, C. Mohila, A.R. Sampson, and D.A. Lewis,
      Lamina-specific alterations in the dopamine innervation of the prefrontal cortex
      in schizophrenic subjects, Am. J. Psychiatry, 156 (1999) 1580-1589]. This
      abnormality may be present early in development, giving rise to dysfunction as an
      individual matures. The present studies examined the effects of early partial
      loss of medial prefrontal cortex (mPFC) DA on DA turnover and locomotor behavior
      in juvenile, pubertal, and adult rats (30, 45, and 60 days of age, respectively).
      Local infusions of 6-hydroxydopamine on postnatal day (PN) 12-14 produced
      persistent decreases in basal tissue DA concentrations and increases in 3,4
      dihydroxyphenylacetic acid (DOPAC):DA ratios in the mPFC. In the nucleus
      accumbens of lesioned rats, basal DA concentrations were decreased and DOPAC:DA
      ratios were increased on PN30, but not PN45 or 60. Footshock (30 min at 0.6 mA)
      increased DOPAC and DOPAC:DA ratios in the mPFC of PN30 and 60 control rats.
      These effects were attenuated in age-matched rats previously sustaining
      approximately 50% loss of mPFC DA on PN12-14. Footshock did not affect DOPAC:DA
      ratios in the nucleus accumbens of control or lesioned rats. The lesion also
      failed to alter basal or stress-evoked motor activity. The present data suggest
      that a decreased density of mPFC DA nerve terminals occurring early in
      development results in persistent alterations in basal and stress-evoked activity
      of mesoprefrontal DA neurons, but not mesoaccumbens DA neurons.

PMID- 16099304
TI  - Developmental expression of cannabinoid receptors in the chick retinotectal
      system.
AB  - The cannabinoid system has been suggested to participate in processes such as
      antinociception, cognition, motor control, and, more recently, development of the
      nervous system. This study describes the expression of the CB1 cannabinoid
      receptor in the developing chick retina and optic tectum by means of conventional
      immunoperoxidase protocols. CB1 immunoreactivity was initially detected around
      the embryonic day 4 (E4) in both the retina and tectum. In the retina, CB1
      immunoreactivity was first observed in presumptive ganglion cells and,
      subsequently, in the inner plexiform layer and two populations of neurons of the
      inner nuclear layer. The post-hatched chick exhibited a pattern of staining that
      included four sublayers of the inner plexiform layer, a few stained cells in the
      ganglion cell layer, and labeled neurons both in the inner and central parts of
      the inner nuclear layer. The latter two types of neurons appear to be amacrine
      and bipolar cells, respectively. In the tectum, CB1 first appeared in its most
      superficial zone and later in several tectal laminae, including a white matter
      layer (stratum album centrale; Cajal's layer 14). There was a remarkable and
      transient increase of labeling at E10, followed by a continuous reduction of
      staining until E18. In the post-hatched chick, tectal staining was mostly
      confined to layers 2-3 and 5-6. Stained perikarya were seldom observed in the
      tectum at any stage. These data are in agreement with a possible developmental
      function of CB1, as it is expressed several days before synaptogenesis ensues and
      exhibits transient expression in the optic tectum.

PMID- 16099305
TI  - Tetrahydrobiopterin and nitric oxide synthase dimer levels are not changed
      following hypoxia-ischemia in the newborn rat.
AB  - The effect of hypoxia-ischemia on the nitric oxide synthase (NOS) cofactor
      tetrahydrobiopterin (BH4) and changes in the enzyme dimer state have not
      previously been studied. Cell-based studies have demonstrated the regulation of
      nitric oxide (NO) synthesis by intracellular BH4 levels. Activation of NOS
      requires two NOS polypeptides to form a homodimer. Dimerization results in the
      creation of high-affinity binding sites for BH4 and L-arginine. Our previous
      studies have indicated that nNOS activity falls 2 h post-hypoxia-ischemia in the
      immature rodent model. Thus, the objective of this study was to determine whether
      changes in nNOS dimeric state could be responsible for the decrease in nNOS
      activity. Using the immature rat model of HI in conjunction with LT-PAGE and
      Western blot analysis, we determined the effect of HI on NOS dimer state in
      hippocampus and cortex and the effects of pharmacologic modulation of NO levels
      during HI on dimer formation. Using high-performance liquid chromatography (HPLC)
      and electrospray tandem mass spectrometry (MS-MS), we measured BH4 and L-arginine
      levels respectively after HI under the same conditions. We found minimal or no
      changes in either BH4 levels or NOS dimer state at 2 h, 24 h and 7 day recovery
      from HI on postnatal day 7. In contrast, L-arginine levels were transiently
      increased in the hypoxic ischemic hemisphere. Thus, our data suggest that the
      previously described decrease in NOS activity after HI is not associated with
      depletion of the cofactor BH4, L-arginine substrate or changes in the NOS enzyme
      dimer state.

PMID- 16099307
TI  - In vivo effect of chronic hypoxia on the neurochemical profile of the developing
      rat hippocampus.
AB  - The cognitive deficits observed in children with cyanotic congenital heart
      disease suggest involvement of the developing hippocampus. Chronic postnatal
      hypoxia present during infancy in these children may play a role in these
      impairments. To understand the biochemical mechanisms of hippocampal injury in
      chronic hypoxia, a neurochemical profile consisting of 15 metabolite
      concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat
      model of chronic postnatal hypoxia using in vivo 1H NMR spectroscopy at 9.4 T.
      Chronic hypoxia was induced by continuously exposing rats (n = 23) to 10% O2 from
      postnatal day (P) 3 to P28. Fifteen metabolites were quantified from a volume of
      9-11 microl centered on the left hippocampus on P14, P21, and P28 and were
      compared with normoxic controls (n = 14). The developmental trajectory of
      neurochemicals in chronic hypoxia was similar to that seen in normoxia. However,
      chronic hypoxia had an effect on the concentrations of the following
      neurochemicals: aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine,
      glutathione, myoinositol, N-acetylaspartate (NAA), phosphorylethanolamine, and
      phosphocreatine/creatine (PCr/Cr) and glutamate/glutamine (Glu/Gln) ratios (P <
      0.001 each, except glutamate, P = 0.04). The increased PCr/Cr ratio is consistent
      with decreased brain energy consumption. Given the well-established link between
      excitatory neurotransmission and brain energy metabolism, we postulate that
      elevated glutamate, Glu/Gln ratio, and GABA indicate suppressed excitatory
      neurotransmission in an energy-limited environment. Decreased NAA and
      phosphorylethanolamine suggest reduced neuronal integrity and phospholipid
      metabolism. The altered hippocampal neurochemistry during its development may
      underlie some of the cognitive deficits present in human infants at risk of
      chronic hypoxia.

PMID- 16099306
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) can act as determinant
      of the tyrosine hydroxylase phenotype of dopaminergic cells during retina
      development.
AB  - In the chick retina, dopaminergic cells are generated between embryonic days 3
      and 7 (E3/E7). However, the expression of tyrosine hydroxylase (TH), the first
      enzyme in the catecholamine synthetic pathway, is only detected after E11/E12.
      During the interval comprising E7 to E12, signals conveyed by cAMP are important
      to determine the TH phenotype. The present study shows that pituitary adenylyl
      cyclase-activating polypeptide (PACAP), via cAMP, is a major endogenous component
      in defining the TH phenotype of retina dopaminergic cells during development.
      PACAP type 1 receptor and its mRNA were detected in retinas since E6. PACAP was
      also immunodetected in cells localized in the inner nuclear layer of retinas
      since E8. This peptide promoted greater than 10-fold increase in cAMP
      accumulation of retinas obtained from embryos since E8, an effect that was
      blocked by PACAP6-38 (PAC1 receptor antagonist). In cultured retina cells from E8
      and E9, maintained for 6 days in vitro with 10 nM PACAP (for 5 days), the number
      of dopaminergic cells expressing tyrosine hydroxylase increased 2.4-fold. The
      cAMP analog, 8-Br-cAMP and 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase
      inhibitor) also increased the number of tyrosine hydroxylase-positive cells by 4-
      to 6-fold. IBMX plus PACAP treatment resulted in 17-fold increase in the number
      of cells positive for tyrosine hydroxylase. Under this condition the amount of
      tyrosine hydroxylase expression, as detected by western blot analysis, was also
      increased. The protein kinase-A inhibitor, rp-cAMPS, significantly reduced the
      effect of PACAP. Our data show that this peptide is an important factor
      influencing the definition of the tyrosine hydroxylase phenotype of retina
      dopaminergic cells within a narrow window of development.

PMID- 16099309
TI  - Cloning, production and functional expression of enterocin P, a sec-dependent
      bacteriocin produced by Enterococcus faecium P13, in Escherichia coli.
AB  - The cloning and expression of enterocin P (EntP), a sec-dependent bacteriocin
      produced by Enterococcus faecium P13, was studied in Escherichia coli. PCR
      amplified products of the preenterocin P gene (entP) or entP plus the putative
      EntP immunity gene (entiP), were cloned in plasmid pETBlue-1 under the control of
      the inducible T7lac promoter. Although target genes in derivative plasmids pJG01
      (entP) and pJG02 (entP plus entiP) did not generate products with antimicrobial
      activity after an in vitro combined transcription/translation reaction, they were
      expressed as biologically active products following transformation and induction
      in the E. coli Tuner(DE3)pLacI host. The use of specific antibodies and an ELISA
      permitted the detection and quantification of EntP in the supernatant (SN),
      cellular soluble protein fraction (CSF), and inclusion bodies (IB) of E. coli
      Tuner(DE3)pLacI cells transformed with either pJG01 or pJG02. Functional EntP
      from the supernatants of E. coli Tuner(DE3)pLacI (pJG01) cultures grown in a
      complex medium was recovered, at a high efficiency, by immunoaffinity
      chromatography in a single step. A purification method based on hydrophobic
      adsorption and reverse-phase chromatographies also permitted the recovery of
      active EntP from the supernatants of the same cultures grown in a minimally
      defined medium. The E. coli Tuner(DE3)pLacI (pJG01) cells would merit
      consideration as an alternative experimental model for the heterologous
      production and functional expression of EntP, as well as for the fast and
      efficient recovery of this bacteriocin from the supernatant of this recombinant
      producer.

PMID- 16099308
TI  - Ontogeny of respiratory sensitivity and tolerance to the mu-opioid agonist
      fentanyl in rat.
AB  - Whereas developmental changes in analgesic sensitivity and tolerance to the mu
      opioid agonist fentanyl have been reported, knowledge of respiratory responses to
      that drug is lacking. Using 7- and 14-day-old (P7, P14) and adult conscious rats,
      we first established, using whole body plethysmography, the fentanyl dose that
      decreased minute ventilation by 50% (ED50) at each age. ED50 increased with
      postnatal age (40, 60 and 120 microg/kg sc, respectively), indicating a high
      sensitivity to fentanyl in the youngest rats that decreased with maturation. In
      separate rat groups of the 3 ages, we injected each ED50 dose, once a day, for
      several consecutive days, until tolerance was established. Tolerance was defined
      as a reduction in respiratory depression from 50% to 75% of baseline. All age
      groups reached tolerance in minute ventilation, respiratory frequency, tidal
      volume and instantaneous flow (equivalent to respiratory drive). The P14 rat pups
      attained tolerance more rapidly (at 2.6 days) than did either the younger (5.1
      days) or the adult rats (4.4 days). These results indicate that respiratory
      sensitivity and tolerance to fentanyl in rat vary in a distinct manner during
      maturation.

PMID- 16099310
TI  - Inactivation kinetics of Yersinia enterocolitica by citric and lactic acid at
      different temperatures.
AB  - Inactivation of Yersinia enterocolitica by citric (1--20% w/v) and lactic (0.3-
      4.0% v/v) acids at different temperatures (4, 20, 40 degrees C) has been
      investigated. Inactivation effect of citric and lactic acids was dependent on
      time and temperature of exposure and acid concentration. Survival curves of Y.
      enterocolitica suspended in citric acid solutions at 4 and 20 degrees C displayed
      a shoulder followed by an exponential inactivation, but at 40 degrees C a
      shoulder was not observed. At all temperatures investigated, survival curves of
      Y. enterocolitica suspended in lactic acid solutions were linear or slightly
      concave upwards. A mathematical model based on the Weibull distribution
      accurately described the kinetics of inactivation of Y. enterocolitica by both
      acids. The influence of the citric acid concentration on Y. enterocolitica
      resistance was independent of the treatment temperature. However for lactic acid,
      the influence of the acid concentration on microbial inactivation depended on the
      temperature. At any temperature investigated, lactic acid was significantly more
      effective than citric acid.

PMID- 16099311
TI  - Relationships between sensorial characteristics and microbial dynamics in
      "Registered Designation of Origin" Salers cheese.
AB  - Raw milk cheeses show a wide diversity of sensorial characteristics, largely
      determined by the microflora of raw milk. Microbial dynamics in Registered
      Designation of Origin (R.D.O.) Salers cheese was assessed by DNA and RNA SSCP
      analysis on nine cheeses. These cheeses showed considerable diversity both in
      microbial dynamics and sensorial characteristics. Relationships between the
      sensorial characteristics and the microbial dynamics were studied. A global
      consideration of bacterial dynamics demonstrated that other bacteria than lactic
      acid bacteria can play a role in the elaboration of sensorial characteristics.
      Indeed, high CG% Gram-positive bacteria can be involved. DNA data, as well as RNA
      data, appeared relevant to attempts to explain sensorial variance. Correlations
      between sensorial and microbial data were rather complex. Several microbial
      variables for DNA and RNA analyses, noted at different times of analysis, were
      correlated to each sensory variable. A global view of cheese microbial community
      proved to be insufficient in explaining the diversity of the sensorial qualities
      of R.D.O. Salers cheese.

PMID- 16099312
TI  - Species-specific PCR-based assays for the detection of Fusarium species and a
      comparison with the whole seed agar plate method and trichothecene analysis.
AB  - Species-specific PCR was used for the identification of nine Fusarium species in
      pure mycelial culture. A PCR-based method was compared with the whole seed agar
      plate method and trichothecene analysis for three toxin-producing Fusarium
      species using 85 grain samples of wheat, barley, oat, corn and rye. A simple SDS
      based DNA extraction system followed by potassium acetate precipitation resulted
      in consistent PCR amplification of DNA fragments from cultures and grain samples.
      The species-specific PCR assays correctly identified pure cultures of Fusarium
      avenaceum ssp. avenaceum (9 isolates), Fusarium acuminatum ssp. acuminatum (12
      isolates), Fusarium crookwellense (7 isolates), Fusarium culmorum (12 isolates),
      Fusarium equiseti (11 isolates), Fusarium graminearum (77 isolates), Fusarium
      poae (10 isolates), Fusarium pseudograminearum (23 isolates), and Fusarium
      sporotrichioides (10 isolates). Multiplex PCR was developed for the simultaneous
      detection of F. culmorum, F. graminearum and F. sporotrichioides, the three most
      important trichothecene producing species in Canada. In grain samples, results of
      PCR assays for these same three species related well with whole seed agar plate
      method results and determination of Fusarium trichothecenes. The PCR assay
      described in this study can be used for routine detection and identification of
      Fusarium spp. in Canada.

PMID- 16099313
TI  - Alcohols, esters and heavy sulphur compounds production by pure and mixed
      cultures of apiculate wine yeasts.
AB  - Strains of Hanseniaspora uvarum, Hanseniaspora guilliermondii and Saccharomyces
      cerevisiae were used as pure or mixed starter cultures in commercial medium, in
      order to compare their kinetic parameters and fermentation patterns. In pure and
      mixed cultures, yeasts presented similar ethanol yield and productivity. Pure
      cultures of H. uvarum and S. cerevisiae showed a specific growth rate of 0.38 h(
      1); however, this value decreased when these yeasts were grown in mixed cultures
      with H. guilliermondii. The specific growth rate of pure cultures of H.
      guilliermondii was 0.41 h(-1) and was not affected by growth of other yeasts. H.
      guilliermondii was found to be the best producer of 2-phenylethyl acetate and 2
      phenylethanol in both pure and mixed cultures. In pure cultures, H. uvarum led to
      the highest contents of heavy sulphur compounds, but H. guilliermondii and S.
      cerevisiae produced similar levels of methionol and 2-methyltetrahydrothiophen-3
      one. Growth of apiculate yeasts in mixed cultures with S. cerevisiae led to
      amounts of 3-methylthiopropionic acid, acetic acid-3-(methylthio)propyl ester and
      2-methyltetrahydrothiophen-3-one similar to those obtained in a pure culture of
      S. cerevisiae; however, growth of apiculate yeasts increased methionol contents
      of fermented media.

PMID- 16099314
TI  - Molecular tools for differentiating probiotic and clinical strains of
      Saccharomyces cerevisiae.
AB  - The subtype of the Saccharomyces cerevisiae yeast species known as S. cerevisiae
      Hansen CBS 5926 was formerly believed to be a separate species, Saccharomyces
      boulardii. It is widely considered non-pathogenic and is used as a probiotic
      agent for treatment and prevention of diarrhea. The biological properties of
      Saccharomyces spp. show considerable intraspecies variability and the beneficial
      properties of probiotic yeasts are considered strain-specific. Septicemia and
      fungemia caused by S. boulardii have recently been described in both
      immunocompromised and immunocompetent patients receiving biotherapy with this
      yeast. It cannot be distinguished from other S. cerevisiae strains by phenotypic
      criteria, so identification of these infections requires molecular typing. To
      identify the most effective approach for distinguishing S. boulardii, we typed 35
      isolates of S. cerevisiae, of which 27 were from various clinical specimens and 8
      were isolates of S. boulardii (6 obtained from probiotic preparations and 2 from
      clinical specimens) using four different molecular methods, two based on PCR
      restriction enzyme analysis or sequencing of rDNA spacer regions, the third based
      on microsatellite polymorphism analysis of the S. cerevisiae genes YKL139w and
      YLR177w, and the last based on hybridization analysis with retrotransposon Ty917.
      Several clinical isolates appeared to be identical to one or more other isolates
      with the first three methods used, whereas with the Ty917 hybridization method
      all of the isolates tested appeared to be very heterogeneous. The eight S.
      boulardii isolates were clearly distinguishable from the clinical S. cerevisiae
      isolates only with Ty917 hybridization and microsatellite DNA analyses. In the
      latter method, the eight S. boulardii isolates exhibited an allelic variant at
      one of loci tested that was not shared with any other strain. Our results suggest
      that microsatellite polymorphism analysis of the YKL139w and YLR177w genes, as
      well as the analysis by Ty917 hybridization, are the most useful tools for a
      correct identification of S. boulardii strains.

PMID- 16099315
TI  - Fungal mycoflora and mycotoxins in Korean polished rice destined for humans.
AB  - Rice samples collected from the Republic of Korea were analyzed for fungal
      mycoflora and mycotoxins: fumonisins, ochratoxin A, trichothecenes, and
      zearalenone. The potential of the fungi to produce each mycotoxin was also
      examined, so that the fungal isolates associated with mycotoxins occurring in
      rice could be verified. Penicillium citrinum and Aspergillus candidus were the
      most prevalent species infecting the samples, while Fusarium proliferatum was
      found as the dominant Fusarium species. Ochratoxin A was the most commonly
      detected mycotoxin analyzed in the present study; moreover, its level in some
      samples was above the EU tolerable limit (3 ng/g). According to rice culture
      experiments, it was revealed that in Korea, fumonisins detected in rice were due
      to F. proliferatum infection, whereas the occurrence of ochratoxin A was caused
      by Penicillium verrucosum, though there were no symptoms of disease in rice found
      in any sample. Furthermore, there appears to be an uneven geographical
      distribution of P. verrucosum as well as ochratoxin A in that most of them are
      found in the rice samples produced in the northern region of Korea.

PMID- 16099316
TI  - Inhibition effect of honey on the adherence of Salmonella to intestinal
      epithelial cells in vitro.
AB  - The aim of the study was to evaluate the antimicrobial effect and the ability of
      honey to prevent Salmonella interitidis adhering to intestinal epithelial cells
      in vitro. Antimicrobial activity was demonstrated. Bacterial adherence was
      assayed using S. interitidis cells that had been incubated first with honey and
      then with the intestinal epithelial cells. Results showed that honey at dilutions
      of up to 1:8 reduced bacterial adherence from 25.6+/-6.5 (control) to 6.7+/-3.3
      bacteria per epithelial cell (P<0.001).

PMID- 16099317
TI  - Innate immune responses to dengue virus.
AB  - Dengue fever/dengue hemorrhagic fever (DF/DHF) has emerged as the most important
      mosquito-borne viral diseases in tropical areas. The dengue virus (DV) has become
      endemic in most tropical urban centers throughout the world, and DHF has appeared
      concomitantly with this expansion. Given the fact that intensity of DV
      replication during the early times of infection could determine clinical
      outcomes, which ranges from febrile illness (DF) to life-threatening disease
      (DHF), it is important to understand the impact of DV infection on innate
      immunity. Interstitial dendritic cells (DCs) are believed to constitute the first
      line of the innate host defense against invading DV at the anatomical sites where
      it replicates after the initial bite by infected mosquito. Early activation of
      natural killer (NK) cells and type-I interferon-dependent immunity may be also
      important in limiting viral replication at the early times of dengue infection.
      The ability of infecting DV to counter the innate antiviral immunity might
      account for differences in virulence observed between viral strains.

PMID- 16099318
TI  - Formation of the cochlear nerve in the modiolus of the guinea pig and human
      cochleae.
AB  - BACKGROUND: Central processes of the bipolar neurons in the spiral ganglion
      converge in the modiolus to form the initial portion of the auditory branch
      (cochlear nerve) of the eighth cranial nerve. This occurs before the cochlear
      nerve passes through the internal auditory meatus. The neurons of the spiral
      ganglion send their central processes towards the internal acoustic meatus,
      through a single canal to form the cochlear nerve. These processes are described
      in many textbooks as running through numerous longitudinal small canals called
      canales longitudinales modioli before entering the internal acoustic meatus.
      Results of this study indicated that the term; "canalis longitudinalis modioli"
      was considered to be more appropriate than the former. METHODS: Central processes
      of the bipolar neurons in the spiral ganglion of the guinea pig and human
      cochleae were investigated using stereo, light and electron microscopy. RESULTS:
      Detailed examination of the guinea pig and human cochleae by light, electron and
      stereomicroscopy did not reveal multiple longitudinal canals but a single canal
      for the cochlear nerve. CONCLUSIONS: The singular term canalis longitudinalis
      modioli is more appropriate than canales longitudinales modioli.

PMID- 16099319
TI  - Protective effect of policosanol on atherosclerotic plaque on aortas in monkeys.
AB  - BACKGROUND: Policosanol is a cholesterol-lowering drug isolated from sugar cane
      wax with concomitant antiplatelet effects. Previous studies have shown that
      policosanol prevents lipofundin-induced atherosclerotic lesions in rabbits and
      rats, including foam cell formation, as well as the development of foam cells in
      carrageenan-induced granulomas in rats. Policosanol also inhibits smooth muscle
      cells proliferation induced on rabbit cuffed artery and on forceps-induced
      arterial wall damage. Furthermore, policosanol administered long term lowered
      serum cholesterol and prevented the development of atherosclerotic lesions in
      Macaca arctoides monkeys. The present study was undertaken to determine whether
      policosanol could change some characteristic features of atherosclerotic lesions,
      such as macrophage number and immunohistochemical localization of apoA-1 and apoB
      in aortas of M. arctoides monkeys. METHODS: Fourteen adult male monkeys weighing
      6-10 kg and receiving a low fat, protein-rich diet were randomly distributed in
      three groups: control group (six monkeys) and two other groups (four
      monkeys/group) treated with policosanol (2.5 and 25 mg/kg) for 54 weeks. Samples
      of arteries were examined by light microscopy. Monoclonal antibodies were used to
      evaluate the presence of macrophage, apoA-1 and apoB. RESULTS: Policosanol
      reduced the presence of macrophages and the occurrence of apoB, whereas increased
      apoA-1 localization in aortic atherosclerotic lesions compared with control
      monkeys. CONCLUSIONS: These results suggest the policosanol potential benefit on
      plaque composition and stability and could explain the protective effects of
      policosanol on atherosclerosis development.

PMID- 16099320
TI  - Gene identification by cDNA arrays in HPV-positive cervical cancer.
AB  - BACKGROUND: One of the most frequent malignancies in women worldwide is carcinoma
      of the uterine cervix. High-risk human papillomavirus (HPV) infection is
      considered the most important etiological factor of uterine cervical cancer. Our
      aim was to identify novel cellular genes that could potentially act as predictive
      molecular markers for human cervical cancer by means of cDNA arrays. METHODS: We
      used cDNA arrays to examine the expression profiles of six cell lines derived
      from human cervical cancer, three HPV+ tumor samples and three normal (HPV-)
      epithelium tissues. Data normalization was performed and the top overexpressed
      genes were obtained. Hierarchical cluster was performed and, to validate some of
      the differentially expressed genes between normal and carcinogenic samples, semi
      quantitative RT-PCR, in situ hybridization and immunohistochemistry were
      performed in tissue samples. RESULTS: Four genes were demonstrated to be
      consistently overexpressed in invasive cervical cancer biopsies; three novel
      genes not previously related to cervical cancer: MMP10, Lamc2 and Claudin 1.
      Moreover, overexpression of IL6 and VEGF was corroborated. CONCLUSIONS: The
      identification of characteristic molecular changes in cervical cells by
      carcinogenesis and HPV infection can lead to a better understanding of cervical
      cancer. cDNA arrays are beginning to provide new possible molecular markers for
      prognosis and diagnosis. This technology could eventually help to elucidate the
      biological differences of the particular mechanisms associated with each
      different HPV-type infection and those with a poor prognosis.

PMID- 16099321
TI  - Resistance of erythrocytes to lipid peroxidation in cirrhotic rats.
AB  - BACKGROUND: The aim of the present study was to investigate erythrocyte
      prooxidant-antioxidant balance in relation to liver and plasma lipid peroxidation
      in thioacetamide (TAA)-induced liver cirrhosis in rats. METHODS: Liver cirrhosis
      was produced by the administration of TAA (0.3 g/L of tap water) for a period of
      3 months in rats. Serum, liver and erythrocyte lipid peroxide levels as well as
      liver glutathione (GSH) levels and superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px) activities were determined in cirrhotic rats. RESULTS:
      Hepatic cirrhosis was assessed by biochemical and histopathological findings.
      Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and
      malondialdehyde (MDA) levels increased in cirrhotic rats. This treatment caused
      increased MDA and diene conjugate (DC) levels as well as decreased GSH levels and
      GSH-Px activities in the liver of cirrhotic rats. In these conditions, no
      significant changes in erythrocyte cholesterol, phospholipid levels as well as
      endogenous DC, and GSH levels and spontaneous hemolysis values were observed in
      erythrocytes of rats with TAA-induced liver cirrhosis. However, H(2)O(2)-induced
      MDA levels were detected to decrease significantly in erythrocytes of cirrhotic
      rats. CONCLUSIONS: Our results indicate that erythrocytes of TAA-induced
      cirrhotic rats have a resistance against peroxidative stress in contrast to the
      findings in plasma and liver.

PMID- 16099322
TI  - Bactericidal activity of different honeys against pathogenic bacteria.
AB  - BACKGROUND: Renewed interest in honey for various therapeutic purposes including
      treatment of infected wounds has led to the search for new antibacterial honeys.
      In this study we have assessed the antibacterial activity of three locally
      produced honeys and compared them to three commercial therapeutic honeys
      (including Medihoney and manuka honey). METHODS: An agar dilution method was used
      to assess the activity of honeys against 13 bacteria and one yeast. The honeys
      were tested at five concentrations ranging from 0.1 to 20%. RESULTS: Twelve of
      the 13 bacteria were inhibited by all honeys used in this study with only
      Serratia marcescens and the yeast Candida albicans not inhibited by the honeys.
      Little or no antibacterial activity was seen at honey concentrations <1%, with
      minimal inhibition at 5%. No honey was able to produce complete inhibition of
      bacterial growth. Although Medihoney and manuka had the overall best activity,
      the locally produced honeys had equivalent inhibitory activity for some, but not
      all, bacteria. CONCLUSIONS: Honeys other than those commercially available as
      antibacterial honeys can have equivalent antibacterial activity. These newly
      identified antibacterial honeys may prove to be a valuable source of future
      therapeutic honeys.

PMID- 16099323
TI  - Estriol induced squamous metaplasia on the nasal mucosa in patients with
      hereditary hemorrhagic telangiectasia.
AB  - BACKGROUND: The aim of this study was to evaluate by light and electron
      microscopy the effect of topical estriol on the nasal mucosa in patients with
      hereditary hemorrhagic telangiectasia (HHT). METHODS: Twelve patients were
      instructed to apply twice daily 0.1% estriol as a nose ointment over a period of
      12 months. Written consent was obtained from each patient, allowing biopsy
      specimens of the nasal mucosa to be taken prior to and 3, 6 and 12 months after
      estriol application. RESULTS: Metaplastic change of the nasal mucosa was observed
      6 months after topical estriol application. The former ciliated columnar
      epithelium changed into a keratinizing squamous epithelium. The effect was
      reversible after discontinuation of estriol application. CONCLUSIONS: For the
      first time, we could outline the effect of topical estriol on the nasal mucosa.
      These histomorphological findings, and the fact that estriol is a low-potency
      metabolite of estradiol, make estriol a valuable agent in the treatment of HHT
      patients.

PMID- 16099324
TI  - ApoE alleles and tau markers in patients with different levels of cognitive
      impairment.
AB  - BACKGROUND: The presence of brain hyperphosphorylated tau constitutes a hallmark
      of neurodegenerative disorders of the Alzheimer's type. This report describes the
      relationships between tau markers in the cerebrospinal fluid (CSF), the degree of
      cognitive impairment and the predictive value of genetic markers such the alleles
      of apolipoprotein E, namely, the presence of Apo-epsilon4, as part of a
      longitudinal study. METHODS: Three major groups of patients with ages ranging
      from 65-73 years were evaluated in this study (n=72): Alzheimer's disease
      patients (AD), a group with mild cognitive impairment (MCI) and normal senile
      patients (NS). Hyperphosphorylated tau and tau dephosphorylated species at the
      Alzheimer-type epitopes in CSF samples were analyzed by ELISA assays using a
      battery of different monoclonal antibodies. ApoE was analyzed by PCR in blood
      samples. RESULTS: The levels of hyperphosphorylated tau were significantly higher
      in AD patients, but no statistical differences were found between the MCI and NS
      groups. However, the analysis of tau markers and cognitive impairment indicated
      the existence of two main subgroups within this population: MCI patients with a
      higher cognitive impairment as revealed by the total box score (TBS) >1.5 who
      exhibited phosphorylated tau patterns similar to the AD group, and patients with
      a mild impairment (TBS <1.5) with tau patterns similar to normal patients. In
      regard to ApoE, epsilon4/epsilon4 genotype was absent in the Chilean population
      analyzed, and only the epsilon2/epsilon4 genotype was significantly increased in
      both MCI and AD patients. A detailed analysis of the ApoE alleles, particularly
      epsilon3 and epsilon4, indicated a tendency to increase the epsilon4 allele in
      the MCI group with higher cognitive impairment and in AD patients. CONCLUSIONS:
      Studies indicate that hyperphosphorylated tau is a good indicator of the degree
      of cognitive disorders in early stages of AD and that no clear correlation exists
      with the epsilon4/epsilon4 and epsilon3/epsilon4 genotypes, even though a higher
      proportion of epsilon4 allele in the MCI group with a more significant level of
      impairment and in AD patients was evidenced.

PMID- 16099325
TI  - Microcirculation disturbances in patients with venous ulcer before and after
      healing as assessed by laser Doppler flux-metry.
AB  - BACKGROUND: We studied whether a characteristic pattern of laser Doppler flux
      (LDF) could be identified in perimalleolar skin of patients with venous ulcer
      before and after ulcer healing. METHODS: Nine subjects with venous ulcer that
      healed after conservative treatment in 1-6 months and nine healthy persons were
      included in the study. Microcirculation investigations of laser Doppler flux
      (LDF) were carried out before and after ulcer healing at rest, upon arterial
      occlusion, during thermal stimulation and during experimental venous
      hypertension. RESULTS: Resting LDF expressed as median and range (in arbitrary
      perfusion units) was significantly higher in patients with venous ulcer in
      comparison to healthy subjects: 60.6 (40.2-156.5) vs. 9.2 (6.5-19.5), p=0.008.
      During thermal stimulation and during postischemic reactive hyperemia, absolute
      values of LDF were slightly but significantly higher in patients with venous
      ulcer than in healthy subjects, but indices of hyperemic reactivity were very low
      in patients (median postischemic LDF increase to 101.8 vs. 450.0% in healthy
      controls, p=0.008; and thermally induced LDF increase to 125.5 vs. 881.5% in
      healthy controls, p=0.008. Experimental venous hypertension (cuff pressure 40 and
      70 mmHg, respectively) led to an equally pronounced relative reduction of LDF in
      healthy persons as in patients with venous ulcer before and after ulcer healing,
      but the absolute values of flow remained about six to seven times higher in
      patients when compared to healthy subjects. Hyperemic reactivity and
      venoarteriolar response did not change after ulcer healing. CONCLUSIONS: Elevated
      basal LDF and preserved maximal LDF during reactive hyperemia were found in
      perimalleolar skin of patients with venous ulcers that eventually healed. The
      relative venoarteriolar response was preserved in spite of elevated absolute
      values of LDF during experimental venous hypertension. These hemodynamic
      characteristics remained unchanged after epithelialization of venous ulcers.

PMID- 16099326
TI  - Lipid-laden alveolar macrophage index in sputum is not useful in the differential
      diagnosis of pulmonary symptoms secondary to gastroesophageal reflux.
AB  - BACKGROUND: Gastroesophageal reflux (GER) is frequently associated with pulmonary
      diseases. Esophageal acid-induced bronchoconstriction and recurrent
      microaspirations of gastric content are the proposed mechanisms. At present there
      is not a sensitive test available to prove a causal relationship between
      pulmonary symptoms and GER. In this study we aimed to investigate the value of a
      marker of aspiration: lipid-laden alveolar macrophage index (LLAM) in induced
      sputum, in the diagnosis of pulmonary symptoms highly suspected to be due to GER.
      METHODS: Twenty-two patients with the endoscopic diagnosis of erosive esophagitis
      who had various pulmonary symptoms that could not be attributed to any apparent
      etiology constituted the study group. Fifteen healthy volunteers with no prior
      diagnosis of gastroesophageal and lung disease constituted the control group.
      Subjects were questioned for pulmonary and abdominal symptoms and underwent
      physical examination, chest radiography, pulmonary function tests, and sputum
      induction. Prepared cytospins were stained with oil red-O to detect cytoplasmic
      lipid droplets and LLAM index was calculated. RESULTS: There was no statistically
      significant difference between the LLAM indexes of the study (1.9 +/- 3.3) and
      control group (4.2 +/- 4.5). LLAM index had a significant positive correlation
      with the duration of reflux symptoms (p=0.01, r=0.5). CONCLUSIONS: LLAM index is
      not found to be a valuable method in the differential diagnosis of pulmonary
      symptoms suspected to be due to GER.

PMID- 16099327
TI  - Venodynamic and hemorheological variables in patients with diabetes mellitus.
AB  - BACKGROUND: The association between diabetes mellitus and the occurrence of
      peripheral vascular disease has been well established. However, it is unclear
      whether the venous circulation is also affected. This study was done to determine
      whether there is impairment of venous function in the legs of patients with
      diabetes mellitus and the relationship with rheological parameters. METHODS:
      Venous occlusion plethysmography was used to assess venous circulation in the
      legs of 54 diabetic patients at the University Hospital of the West Indies. The
      venodynamic variables measured were segmental venous capacitance (SVC), maximum
      venous outflow (MVO), and venous emptying time (VET) at the calf, ankle and great
      toe. Plasma fibrinogen concentration (PFC), relative plasma viscosity (RPV) and
      whole blood viscosity (WBV) were measured by standard techniques. RESULTS: Calf
      SVC was significantly less in neuropathic diabetic patients (ND) than in non
      diabetic subjects (C) (p <0.05). MVO at the calf of ND and non-neuropathic
      diabetic patients (NND) was significantly lower than in C (p <0.05). VET at the
      ankle and calf were significantly shorter in ND compared with NND (p <0.05). No
      statistically significant differences in SVC, MVO and VET among the three groups
      were observed at the great-toe. PFC was significantly higher in diabetic patients
      than in the control group. No significant differences were detected in WBV at
      high or low shear rates. CONCLUSIONS: These findings strongly suggest impairment
      of venous function in the legs of diabetic patients. This impairment of venous
      function appears to be unrelated to rheological abnormalities.

PMID- 16099328
TI  - Hypersplenism in schistosomatic portal hypertension.
AB  - BACKGROUND: For many years, the hematologic changes occurring in hepatosplenic
      Manson's schistosomiasis have been defined as hypersplenism. Initially, the
      belief was that removal of the spleen would normalize the hematologic values.
      However, hematimetric normalization was observed in surgeries for the treatment
      of portal hypertension in which the spleen was preserved. In view of these
      findings, it is necessary to verify the clinical and laboratory profile of these
      patients in order to define the real presence of hypersplenism. METHODS: This
      study was conducted on 51 patients with schistosomatic portal hypertension
      divided into five groups: group 1, non-operated patients under clinical control;
      group 2, patients submitted to distal splenorenal shunt; group 3, patients with
      subtotal splenectomy and central splenorenal shunt; group 4, patients with total
      splenectomy and central splenorenal shunt; and group 5, patients with total
      splenectomy and portal-variceal disconnection. Clinical signs of hypersplenism
      were assessed in all patients. Hematologic values of the pre- and postoperative
      period were compared. Immunoglobulin counts of the patients were verified in the
      late postoperative period. RESULTS: In all operated groups, hematimetric values,
      leukocyte counts, platelet number and prothrombin time were higher during the
      postoperative period. With respect to the immunoglobulins, the postoperative
      values of IgM, IgG and IgA were normal. CONCLUSIONS: Patients with schistosomatic
      portal hypertension and peripheral cytopenia cannot be classified as having
      hypersplenism but rather as having pancytopenia due to splenomegaly caused by
      difficulty on portal blood drainage.

PMID- 16099329
TI  - Leukocyte oxidant and antioxidant status in asthmatic patients.
AB  - BACKGROUND: Oxidative stress mediated by reactive oxygen species (ROS) is
      recognized to contribute significantly to the inflammatory process of bronchial
      asthma (BA). These species are released into the airway by activated inflammatory
      cells such as leukocytes. In this study, we aimed to determine whether the
      oxidant-antioxidant balance is changed in leukocytes of patients with BA.
      METHODS: Thirty eight patients (21 male, 17 female) aged 22-68 years and controls
      of 32 subjects (18 male, 14 female) aged 20-63 years were included in the study.
      A total of 10 mL venous blood was drawn, leukocytes were separated and lipid
      peroxidation (LPO), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD)
      and vitamin C levels were determined in both patients and controls. RESULTS:
      Leukocyte LPO and SOD activity in the patient group were higher than that of
      controls (p <0.001 and p <0.05, respectively). However, leukocyte GSH-Px and
      vitamin C levels in the patient group were lower than that of controls (p <0.01
      and p <0.001, respectively). CONCLUSIONS: The results suggest that there are
      alterations in a wide array of oxidants and antioxidants with balance shifting
      toward increased oxidative stress in BA.

PMID- 16099330
TI  - Auditory impairment in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: We assessed the auditory function of 94 patients with type 2 diabetes
      mellitus and 94 age- and sex-matched healthy subjects. METHODS: To study the
      influence of the clinical characteristics of the disease on the auditory
      function, after a clinical interview with ophthalmological assessment, subjects
      were evaluated using pure-tone audiometry, speech audiometry, auditory brainstem
      responses, the Michigan Diabetic Neuropathy Score and albuminuria. The mean age
      when diabetes was diagnosed was 42.8 +/- 6.5 years (mean +/- SD) and the time
      elapsed since diabetes diagnosis was 7.2 +/- 5.4 years. RESULTS: Forty-eight
      patients (62%) had HbA1c >8%; diabetic retinopathy was evident in 14 patients
      (14%) and microalbuminuria was identified in 12 patients. Compared to healthy
      subjects, diabetic patients showed an increase of the perception threshold at
      8000 Hz (p <0.01), higher hearing levels to discriminate at least 90% of 10
      monosyllables (p <0.01), and longer latencies of wave V, interwave I-V and
      interwave III-V (p <0.01). Significant correlation was found between the hearing
      threshold at 8 KHz and patient age, and the former and the time elapsed since the
      diabetes was diagnosed (p <0.001). CONCLUSIONS: Patients with type 2 diabetes
      mellitus can have subclinical hearing loss and impaired auditory brainstem
      response, independent of peripheral neuropathy, retinopathy or nephropathy.

PMID- 16099331
TI  - Genetic polymorphisms of estrogen receptors in patients with premature coronary
      artery disease.
AB  - BACKGROUND: Estrogen protects against atherosclerosis through its
      genomic/nongenomic effects. Estrogen receptors (ESR) alpha (1) and beta (2)
      mediate much estrogen action. Both receptors exist in the arterial wall, but the
      extent of their distribution in arterial layers is unknown. Allelic variants of
      the gene encoding ESR1 and ESR2 may alter their expression and function,
      resulting in genetic variability. METHODS: In the present age-adjusted, case
      control study, the prevalence of four mutations in estrogen receptors was
      analyzed in patients with premature CAD and controls. RESULTS: Mutation in the
      ESR1 (PvuII) was more prevalent in the controls (18 vs. 11%; p=0.062) than in CAD
      patients, and the mutation identified by the XbaI enzyme in the same receptor was
      associated with reduced apolipoprotein B levels and low body mass index. Mutation
      of the ESR2 (AluI) was more prevalent in CAD patients (0.6 vs. 18%; p=0.008).
      Homozygosis for this mutation involved increased body mass index, elevated serum
      triglycerides and apolipoprotein B, and reduced HDL-cholesterol. Multivariate
      logistic regression analysis showed dyslipidemia, low serum HDL levels, and ESR2
      polymorphism (AluI) [OR=1.89 (95% CI: 1.08-3.34); p=0.034] to be independent risk
      factors for CAD. CONCLUSIONS: Our data suggest that mutation of the ESR2 is an
      independent risk marker for premature CAD.

PMID- 16099332
TI  - Effect of vascular endothelial growth factor on fibroblasts from external
      auditory canal cholesteatoma.
AB  - BACKGROUND: EACC is a disease of the external auditory canal resulting in
      destruction of adjacent tissue. However, the role of the surrounding mesenchymal
      fibroblasts of the perimatrix still remains unclear. In this study we treat
      isolated fibroblasts of EACC with VEGF and determine FGF-2 levels. We also treat
      the fibroblast cultures with FGF-2 and measured VEGF levels. METHODS: All EACC
      cell cultures were obtained from five patients undergoing surgery and used at
      passage 3. After 1-4 days incubation with 50 ng/mL FGF-2, and 1-8 days incubation
      with 50 pg/mL VEGF incubation, the expression of the FGF-2 and VEGF protein in
      the supernatants of the HGF/SF-treated and -untreated culture cell lines was
      analyzed, respectively. RESULTS: After 8 days of incubation with 50 ng/mL VEGF,
      the levels of FGF-2 decreased. However, after 4 days of incubation with FGF-2 the
      VEGF levels increased significantly in treated tissue culture (p <0.05) in
      comparison to untreated EACC fibroblasts. The total protein concentration showed
      no significant difference in both cultures (p >0.05). CONCLUSIONS: In summary,
      exogenous FGF-2 increased fibroblast expression of VEGF, which is a major
      autocrine mediator of FGF-2-induced angiogenesis and proliferation. However,
      incubation with VEGF resulted in decrease of FGF-2 levels. Regarding the slow
      growth of the fibroblasts, they may not be as likely to exhibit a reactive or
      invasive phenotype as seen in middle ear cholesteatoma fibroblasts.

PMID- 16099333
TI  - Erythrocyte adaptation to oxidative stress in endurance training.
AB  - BACKGROUND: We tested the hypothesis that endurance training may reduce exercise
      oxidative stress damage on erythrocytes. METHODS: Fifteen subjects performed a
      standardized endurance exercise at 75% of maximal oxygen consumption weekly
      during a 19-week training period. Blood samples taken before and after exercise
      were analyzed by Fourier transform-infrared (FT-IR) spectrometry to determine
      exercise-induced change in plasma concentrations and erythrocyte IR absorptions.
      RESULTS: Training first induced a stabilization of plasma concentration changes
      during exercise (unchanged for glucose, increased for lactate, triglycerides,
      glycerol, and fatty acids), whereas erythrocyte phospholipid alterations remained
      elevated (p <0.05). Further, training reduced the exercise-induced erythrocyte
      lactate content increase (nuC-O; p <0.05) and phospholipid alterations (nuC-H(n)
      and nuP=O; p <0.05) during exercise. These changes paralleled the decrease of
      exercise-induced hemoconcentration (p <0.05) and plasma lactate increase (p
      <0.05). CONCLUSIONS: These correlated changes between plasma and erythrocyte
      parameters suggest that endurance training reduces erythrocyte susceptibility to
      oxidative stress.

PMID- 16099334
TI  - Cold injury syndrome and neurodevelopmental changes in survivors.
AB  - BACKGROUND: The aim of this study was to extend and develop knowledge of the
      clinical parameters of cold injury syndrome (CIS) in hypothermic infants and
      newborns, so that morbidity, mortality, and neurodevelopmental disturbances
      associated with the condition can be reduced. METHODS: This retrospective, 10
      year cohort study investigated 103 hypothermic infant and newborn patients (aged
      0-60 days) admitted to the Pediatric Department between January 1, 1976 and
      December 31, 1985. Medical records of 67 survivors and 36 children who died were
      analyzed. Of the survivors, 24 consented to undergo assessment of
      neuropsychological and neurodevelopmental outcomes. RESULTS: At presentation, all
      patients manifested cold skin and limbs, while 96 (93.2%) were sleepy, hypotonic
      and inactive. Cyanosis with bradycardia, bradypnea, and apneic crisis (AC) was
      observed in 80 (77.7%) patients, and 65 (63.1%) demonstrated diffuse
      intravascular coagulation (DIC). Pulmonary hemorrhage, AC, respiratory distress
      syndrome, and DIC represented the primary causes of death. Higher body
      temperatures on admission reduced the risk of death. Of the 24 patients assessed
      for neuropsychological and neurodevelopmental outcomes, all but one had normal
      intellectual capabilities, whereas 16 (66.7%) showed signs of neurodevelopmental
      disturbances. CONCLUSIONS: The severity of hypothermia, leukopenia, and
      thrombocytopenia with DIC correlates with prognosis and death rate. Hypothermia
      in infants and newborns can cause psychological and neurodevelopmental
      disturbances in survivors.

PMID- 16099335
TI  - Plasma prekallikrein as a risk factor for diabetic retinopathy.
AB  - BACKGROUND: The aim of the study was to verify the hypothesis that in diabetes
      there is an increased activation of coagulation system leading in consequence to
      diabetic retinopathy. METHODS: Thirty three healthy subjects (controls, 16 males
      and 17 females) and 35 patients with diabetes type 1 (15 males and 20 females)
      were examined. We monitored plasma prekallikrein (PPK), glycemia, fructosamine,
      glycosylated hemoglobin, activated partial thromboplastin time (PTT), INR,
      fibrinolysis in euglobulins time (FET), level of antithrombin III (AT III),
      fibrinogen (Fb) and fibrinogen degradation products (FDP). RESULTS: In diabetic
      patients without retinopathy, PKK concentration was 16% higher (p <0.005), in
      patients with background retinopathy 33% higher (p <0.001), and in patients with
      proliferative retinopathy PKK concentration was 50% higher (p <0.001) than in
      controls. In the subgroup of patients with proliferative retinopathy PTT was
      significantly shorter (p <0.001), and FET was significantly longer (p <0.001)
      than in control. In patients with diabetes higher FDP concentrations were found
      than in controls (p <0.05). Significant correlations were found between PPK and
      fructosamine levels in all diabetic patients (R(S)=+0.57 p <0.001), in diabetic
      patients without retinopathy (R(S)=+0.61, p <0.05), and in diabetic patients with
      retinopathy (R(S)=+0.62, p <0.005). We found negative correlation between PPK
      concentration and PTT (R(S)=-0.43, p <0.001) and positive correlation between PPK
      concentration and FET (R(S)=+0.59, p <0.00001) in the entire study group.
      CONCLUSIONS: The occurrence of diabetic retinopathy is connected with higher
      levels of plasma prekallikrein.

PMID- 16099336
TI  - Increased plasma aldosterone in patients with clinical depression.
AB  - BACKGROUND: Clinical depression has been increasingly recognized as an
      independent risk factor for adverse cardiovascular events, but the biological
      mechanisms of this association remain unclear. Recent evidence for renin system
      dysregulation in patients with depression led us to hypothesize that aldosterone-
      a well-recognized contributor to vascular injury--could be increased in depressed
      patients. The present study was designed, therefore, to be a cross-sectional
      investigation of plasma renin and aldosterone levels in depressed patients as
      compared with healthy controls with no history of psychiatric illness. METHODS: A
      total of 65 depressed patients and 65 age- and gender-matched control subjects
      were enrolled. Following a fixed sodium and potassium diet, venous blood samples
      were obtained at 9:00 a.m. to avoid the influence of circadian rhythms. RESULTS:
      Although there were no significant differences in plasma level of renin among
      subjects with depression and controls (7.9 +/- 5.8 vs. 6.4 +/- 4.3 pg/mL,
      respectively; p=0.10), depressed subjects exhibited greater mean aldosterone
      levels as compared with control subjects (157.2 +/- 67.5 vs. 125.7 +/- 38.1
      pg/mL, respectively; p=0.0014). After adjusting for potential confounders,
      multivariate logistic regression analysis showed that subjects with depression
      had 2.77 times higher odds of elevated aldosterone levels compared with healthy
      control subjects (95% confidence interval, 1.30-5.92, p=0.008). CONCLUSIONS: Our
      present findings support the hypothesis that hyperaldosteronism could be a common
      feature among depressed patients, thereby suggesting that increased aldosterone
      levels may act as a mediator in the pathway linking depression to unfavorable
      vascular events.

PMID- 16099337
TI  - Ozone therapy effects on biomarkers and lung function in asthma.
AB  - BACKGROUND: The relationship and behavior of serum immunoglobulin E (IgE) level,
      peripheral blood mononuclear cell (PBMC) human leukocyte antigen DR (HLA-DR)
      expression and erythrocyte glutathione antioxidant pathway in asthma patients
      treated with systemic ozone therapy have not been studied before. METHODS: Asthma
      patients were treated about 1 year with three cycles (5 or 6 months each) with
      three different ozone therapy protocols. Ozone major autohemotherapy (MAHT) was
      applied at doses of 4 and 8 mg, 15 sessions each cycle; and ozone rectal
      insufflations (RI) at a dose of 10 mg, 20 sessions each cycle. Serum IgE, HLA-DR
      expression in PBMC and biomarkers for antioxidant pathway were measured before
      and at the end of each cycle. Lung function and symptoms test were recorded at
      the beginning and after the third cycle. RESULTS: IgE and HLA-DR decreased with
      the three types of treatments, while increments in reduced glutathione,
      glutathione peroxidase, glutation reductase and glutathione S-transferase were
      achieved with all treatments. Lung function and symptoms test were markedly
      improved. However, in all parameters the best response was obtained in the order:
      MAHT at 8 mg better than MAHT at 4 mg better than RI at 10 mg. Before ozone
      treatment, glutathione antioxidant parameters were under the normal reference
      values, suggesting the occurrence of oxidative stress associated with atopic
      asthma. CONCLUSIONS: This study demonstrates the effectiveness of ozone therapy
      in reducing IgE and inflammatory mediators along with the induction of
      antioxidant elements. The study raises the role of systemic ozone therapy in
      atopic asthma by means of its immunomodulatory and oxidative stress regulation
      properties.

PMID- 16099338
TI  - Tumor necrosis factor-alpha microsatellite polymorphism association with
      rheumatoid arthritis in Indian patients.
AB  - BACKGROUND: Level of TNF-alpha increases significantly in synovial fluid of
      rheumatoid arthritis (RA) patients. It is proposed that tumor necrosis factor
      (TNF) microsatellite alleles may influence its expression and presumably can
      contribute to the disease severity. However, there is a lack of such study to
      predict any such association with RA in an Indian population. METHODS: In this
      study, we investigated the differential pattern of distribution of TNF
      microsatellite alleles in an Indian population and its association with RA. One
      hundred eighteen RA patients and 120 healthy individuals were genotyped for TNF
      microsatellite alleles using Genescan. Odds ratio was calculated to demonstrate
      the correlation between allelic distribution and clinical severity. RESULTS: The
      study shows that distribution of TNF microsatellite alleles in an Indian
      population is very different from other Asian Oriental and Western populations,
      except for some similarities with an Italian population. Frequency of
      microsatellite TNFd3 allele (9.24 vs. 3.85%, chi(2)=5.6, p < or =0.0179,
      OR=0.393, 95% CI=0.177-0.87) and more interestingly TNFd3 containing haplotypes
      has been found significantly reduced in patients. On the contrary, TNFb5 allele
      frequency increased in the patients (22.3 vs. 30.8%, chi(2)=4.4, p < or =0.036,
      OR=1.55, 95% CI=1.027-2.344) as compared to controls. Furthermore, significant
      increase in frequency of this allele in severe patients (22.3 vs. 33.8%,
      chi(2)=6.22, p < or =0.013, OR=1.78, 95% CI=1.132-2.798) along with the
      significant increase in haplotypes containing this allele supports the
      association of TNFb5 with disease severity. CONCLUSIONS: In an Indian population,
      TNFb5 may be considered as a risk factor, whereas TNFd3, unlike others, may be
      protective for RA.

PMID- 16099339
TI  - Cost of AIDS care in Mexico: what are its main individual predictors?
AB  - BACKGROUND: The Mexican government is offering universal access to antiretroviral
      (ARV) drugs. The cost of doing so, despite aggressive price negotiation with the
      pharmaceutical industry, remains high. Even with a low prevalence, about 150,000
      Mexicans are estimated to be living with HIV and will require ARV treatment.
      Estimating the resources needed to fund this gap should consider how patient and
      provider characteristics affect health care costs. METHODS: Using a sample of
      patients from 11 facilities in three Mexican cities representing a large
      proportion of AIDS patients in the country, we developed a fixed-effect model,
      which by controlling the facilities and individual heterogeneity estimates
      predicted costs using patient demographic and socioeconomic characteristics as
      well as physician training. RESULTS: The estimated model explains about 45% of
      the variation in costs. Additional education is significantly and positively
      associated with cost. Increasing age is also associated with higher costs.
      CONCLUSIONS: Socioeconomic status and demographic characteristics explain an
      important proportion of variation in care costs for AIDS, despite AIDS being such
      a heterogeneous disease. Such characteristics will need to be taken into account
      when resource needs are estimated. A priority-setting process considering the
      principles of equity in the fair distribution of resources is needed to help
      reduce the social burden of HIV/AIDS in Mexico.

PMID- 16099340
TI  - Association of working conditions and lifestyle with increased serum gamma
      glutamyltransferase: a follow-up study.
AB  - BACKGROUND: This study investigated the association of working conditions and
      lifestyle with the development of increased serum gamma-glutamyltransferase (GGT)
      in Japanese workers. METHODS: A follow-up study was carried out on workers of a
      telecommunication enterprise who received their first annual health check-up
      between 1992 and 1996, when they were between 40 and 54 years of age. Workers who
      had high serum GGT (> or =60 IU/L in males, > or =30 IU/L in females), a past
      history of disease, or current illness at their first check-up were excluded from
      the analysis. In total, the study included 15,586 workers. The association
      between working conditions and lifestyle and development of increased serum GGT
      (> or =60 IU/L in males, > or =30 IU/L in females) was investigated by pooled
      logistic regression analyses. RESULTS: In males, body mass index, consumption of
      alcohol (<2 times/week, 2-5 times/week, >5 times/week), smoking (<20
      cigarettes/day, > or =20 cigarettes/day), rarely taking three meals a day, marked
      preference for salty meals, and little preference for vegetables were positively
      associated with the development of increased serum GGT. Preferences for fatty
      meals (marked, moderate) were negatively associated with the development of
      increased serum GGT. In females, age and BMI were positively associated with the
      development of increased serum GGT. CONCLUSIONS: Applying a new statistical
      analysis to this retrospective cohort study of 5 years, we revealed the health
      influences of alcohol consumption, smoking and eating habits on increased serum
      GGT. On the other hand, this study indicated that shift work or other working
      conditions are not significant risk factors for increased serum GGT.

PMID- 16099341
TI  - Sexual behavior and herpes simplex virus 2 infection in college students.
AB  - BACKGROUND: Given the relevance of HSV-2 infection in youth, the aim of this
      study was to determine the seroprevalence of HSV-2 in college students in
      Cuernavaca, Mexico, as well as the sociodemographic and sexual behavioral
      characteristics associated with this infection. METHODS: A cross-sectional study
      was carried out using convenience sampling with consenting students of both
      genders. Students answered a questionnaire and provided a blood sample to detect
      antibodies to HSV-2 by Western blot. To establish the magnitude of the
      association between the prevalence of HSV-2 infection and the selected risk
      factors, we estimated prevalence odds ratios by performing logistic analyses of
      these results RESULTS: Overall seroprevalence of HSV-2 was 5.9% (20/340; CI(95%)
      3.7-8.9), 7.0% (14/200; CI(95%) 3.9-11.5) for women and 4.3% (6/140; CI(95%) 1.6
      9.1) for men. HSV-2 infection was independently associated with female sex
      (POR=5.3, CI(95%) 1.4-19.7), age (26 years and over, POR=4.7, CI(95%) 1.0-22.2),
      number of sexual partners over the last year (two or more partners POR=4.1,
      CI(95%) 1.2-14.2), a history of genital ulcers (POR=6.1, CI(95%) 1.9-19.8), and
      having been paid for sex (POR=21.4, CI(95%) 1.0-447.5). CONCLUSIONS: The
      frequency of HSV-2 infection among these students was lower than in other Mexican
      populations who have high-risk sexual behavior. However, there was a subgroup of
      participants identified as having high-risk sexual behavior. These individuals
      could, therefore, be prone to acquiring and transmitting HSV-2 infection and
      represent the target group for whom preventive interventions against HSV-2 and
      other STIs might be developed.

PMID- 16099342
TI  - Predictive performance of anthropometric indexes of central obesity for the risk
      of type 2 diabetes.
AB  - BACKGROUND: In spite of several available anthropometric indexes, the relative
      merit of these indexes for the prediction of type 2 diabetes remains unknown.
      Considering that obesity and diabetes commonly coexist as co-morbidities, our
      objective was to directly compare the performance of measures of central and
      general obesity to predict the risk of type 2 diabetes. METHODS: We conducted a
      case-control study of type 2 diabetes on 150 cases and 150 age- and gender
      matched controls. We directly compared the predictive performance of five
      anthropometric indexes: four related to central obesity--waist circumference
      (WC), waist/hip ratio (WHR), abdominal volume index (AVI) and conicity index
      (CI); and one related to general obesity--body mass index (BMI). We used various
      statistical approaches like area under (AUC) receiver-operating characteristic
      (ROC) curves, likelihood ratios, logistic regression and Shannon's entropy to
      compare the performance of the indexes in the study sample as well as
      bootstrapped samples. RESULTS: WC had the highest overall predictive accuracy
      that was gender insensitive (AUC=0.77 in males and 0.74 in females); a comparable
      information content as that of AVI (Shannon's entropy=1.81 for WC and 1.84 for
      AVI) and was a better predictor of the risk of type 2 diabetes than all the
      remaining indexes. WC also correlated strongly with the biochemical markers of
      diabetes like blood sugar and lipid profile. CONCLUSIONS: WC is a simple, non
      invasive and accurate predictor of the risk of type 2 diabetes that can
      potentially be used in screening programs in developing countries.

PMID- 16099343
TI  - Cytomegalovirus excretion in children attending day-care centers.
AB  - BACKGROUND: Healthy children attending day-care centers (DCC) may excrete
      cytomegalovirus (CMV) frequently. Mothers of children excreting CMV are at higher
      risk for acquiring this infection than mothers of children not excreting CMV.
      Despite the increased attendance to DCC by children there is a lack of
      information regarding CMV infection in Mexico. METHODS: Prospective determination
      of CMV excretion in saliva of children attending public and private DCC. Three
      saliva samples were collected during a 2-month follow-up period from
      participating children and the presence of CMV was determined by viral culture.
      Demographic features of children and DCC type were taken into account when
      comparing children with and without CMV excretion. RESULTS: One hundred fifty-two
      children participated in the study (84 from public and 68 from private DCC).
      Overall, 17 (11.2%) children excreted CMV during the study period. Excretion
      rates varied between DCC from 3.1 to 31.3%. Children from private DCC were as
      likely to excrete CMV as children from public DCC. There were no demographic or
      clinical features of children associated with viral excretion. CONCLUSIONS: CMV
      was excreted on an average of 11.2% children attending DCC. The type of DCC or
      other demographic features were not associated with the likelihood of CMV
      excretion. CMV seronegative mothers of children who attend DCC need to be aware
      of the possibility of CMV acquisition and transmission in DCC.

PMID- 16099344
TI  - Workload and health complaints in overtime workers: a survey.
AB  - BACKGROUND: In epidemiological studies on workload and complaints on health, the
      dose-response relationship should be assessed to design a strategy for the
      prevention of disease or disability. Evaluation for the relationship between
      workload and complaints were urgently required. METHODS: The study population
      consisted of 109 male workers at a car manufacturer workplace. These observations
      were analyzed to determine exposure to load and subjective complains by
      standardized questionnaire. Workloads of the target subjects were divided into
      four groups (A to D), according to the scores of a self-administered
      questionnaire. RESULTS: Percentage of feeling stressful to each of seven items
      such as overtime work, irregular work, official trip, nighttime work, no rest
      and/or no nap, mental workload, and physical workload were 62.4, 34.9, 0.9, 23.9,
      18.3, 65.1, and 33.9%, respectively. Pearson's moment correlation coefficient
      between workload and health complaint was 0.585. After adjusting for age, it
      became 0.586. Furthermore, odds ratio of the subjects who were grouped into C or
      D were 13.6 (95% confidence interval 3.0 to 61.4) and 48.0 (95% confidence
      interval 4.3 to 537.3) against group A, which were all significant. CONCLUSIONS:
      There was a significant relationship between workload and health complaints in
      this questionnaire survey. To prevent or lower complaints of workers,
      improvements of working conditions such as overtime work are recommended to
      reduce health risk.

PMID- 16099345
TI  - Sub-optimal fetal iron acquisition under a maternal environment.
AB  - Iron deficiency acquired at an early age can lead to significant developmental
      alterations. To evaluate the need for an interventional trial, we determined the
      iron reserves of neonates born to a group of women from an urban disadvantaged
      group. The influence of maternal iron on newborn hemoglobin, birth weight, and
      height was also analyzed. Hemoglobin and serum ferritin (SF) concentrations were
      measured at delivery on 201 neonates and their mothers. Neonatal iron stores were
      considered deficient when the cord SF concentration was <12.0 microg/L, reduced
      if > or =12.0 but <30 microg/L, and replenished when > or =30 microg/L. The same
      cut-offs applied to maternal SF values. Cord SF in the study group was 81.2 +/-
      63 microg/L. Following the criteria adopted for this study, three groups of
      neonates were identified. I: 13 (6.5%) were born with deficient iron stores, II:
      15 (7.5%) had reduced iron stores, and III: 173 (86%) had normal levels of
      storage iron. Cord SF concentrations were 7.1 +/- 3.5, 19.9 +/- 4.4 and 92 +/- 60
      microg/L, respectively. Cord hemoglobin did not differ among groups. Iron stores
      at birth were reduced when maternal stores were deficient, reflecting a limited
      fetal iron-acquisition capacity and the restrictive effect of gestational iron
      deficiency on the constitution of adequate fetal iron reserves. These findings
      support the need for an interventional trial on the study population. Hemoglobin,
      birth weight, and height did not correlate with fetal or maternal iron stores.

PMID- 16099346
TI  - Relationship between grip strength and hand bone mineral density in healthy
      adults.
AB  - The aim of this study was to assess site-specific relationship of hand bone
      mineral density (BMD) with hand size, pinch and grip strength in healthy people
      aged 19-50 years. A total of 143 healthy volunteers participated in the study
      (mean age: 34 years). One hundred-six were premenopausal women (mean age: 34
      years) and 37 were men (mean age: 34 years). Grip and pinch strength was measured
      by a Jamar dynamometer (Jamar, Irvington, NY). Second, third and fourth middle
      phalanx BMD were measured on a MetriScan densitometer (Hayward, CA) and mean
      value of these three phalanxes were used in the analysis. There was not a
      significant correlation between hand BMD and grip, pinch strength or hand size in
      premenopausal women. A significant correlation between hand BMD and grip strength
      was found in men (right hand; r=0.44, p=0.007, left hand; r=0.33, p=0.05). Hand
      size was not correlated with hand BMD both in men and in women. The short-term
      precision for RA was estimated as 0.44%. This is the first report of a site
      specific relationship of BMD measured by radiographic absorptiometry with hand
      size, pinch and grip strength in healthy men and premenopausal women. Our results
      revealed that there is a moderate correlation between hand-grip strength and hand
      BMD in men. Hand size does not predict hand BMD both in men and women.
      Radiographic absorptiometry is a practical and reproducible method to detect bone
      mineral density of hands and may be a valuable screening tool for osteoporosis.

PMID- 16099347
TI  - Prevalence of hepatitis C virus genotypes in a Mexican population.

PMID- 16099348
TI  - Aloe linked to thyroid dysfunction.

PMID- 16099349
TI  - Listening to action-related sentences modulates the activity of the motor system:
      a combined TMS and behavioral study.
AB  - Transcranial magnetic stimulation (TMS) and a behavioral paradigm were used to
      assess whether listening to action-related sentences modulates the activity of
      the motor system. By means of single-pulse TMS, either the hand or the foot/leg
      motor area in the left hemisphere was stimulated in distinct experimental
      sessions, while participants were listening to sentences expressing hand and foot
      actions. Listening to abstract content sentences served as a control. Motor
      evoked potentials (MEPs) were recorded from hand and foot muscles. Results showed
      that MEPs recorded from hand muscles were specifically modulated by listening to
      hand-action-related sentences, as were MEPs recorded from foot muscles by
      listening to foot-action-related sentences. This modulation consisted of an
      amplitude decrease of the recorded MEPs. In the behavioral task, participants had
      to respond with the hand or the foot while listening to actions expressing hand
      and foot actions, as compared to abstract sentences. Coherently with the results
      obtained with TMS, when the response was given with the hand, reaction times were
      slower during listening to hand-action-related sentences, while when the response
      was given with the foot, reaction times were slower during listening to foot
      action-related sentences. The present data show that processing verbally
      presented actions activates different sectors of the motor system, depending on
      the effector used in the listened-to action.

PMID- 16099350
TI  - Spatial processing in human auditory cortex: the effects of 3D, ITD, and ILD
      stimulation techniques.
AB  - Here, the perception of auditory spatial information as indexed by behavioral
      measures is linked to brain dynamics as reflected by the N1m response recorded
      with whole-head magnetoencephalography (MEG). Broadband noise stimuli with
      realistic spatial cues corresponding to eight direction angles in the horizontal
      plane were constructed via custom-made, individualized binaural recordings (BAR)
      and generic head-related transfer functions (HRTF). For comparison purposes,
      stimuli with impoverished acoustical cues were created via interaural time and
      level differences (ITDs and ILDs) and their combinations. MEG recordings in ten
      subjects revealed that the amplitude and the latency of the N1m exhibits
      directional tuning to sound location, with the amplitude of the right-hemispheric
      N1m being particularly sensitive to the amount of spatial cues in the stimuli.
      The BAR, HRTF, and combined ITD + ILD stimuli resulted both in a larger dynamic
      range and in a more systematic distribution of the N1m amplitude across stimulus
      angle than did the ITD or ILD stimuli alone. Further, the right-hemispheric
      source loci of the N1m responses for the BAR and HRTF stimuli were anterior to
      those for the ITD and ILD stimuli. In behavioral tests, we measured the ability
      of the subjects to localize BAR and HRTF stimuli in terms of azimuthal error and
      front-back confusions. We found that behavioral performance correlated positively
      with the amplitude of the N1m. Thus, the activity taking place already in the
      auditory cortex predicts behavioral sound detection of spatial stimuli, and the
      amount of spatial cues embedded in the signal are reflected in the activity of
      this brain area.

PMID- 16099351
TI  - Phenytoin reverses the chronic stress-induced impairment of memory consolidation
      for water maze training and depression of LTP in rat hippocampal CA1 region, but
      does not affect motor activity.
AB  - Previous studies have shown that phenytoin can protect hippocampal structure from
      damage by chronic stress, while whether it can reverse the hippocampal
      malfunction induced by chronic stress is unknown. We investigated the effects of
      phenytoin on motor activity of stressed rats and on the long-term memory of water
      maze spatial training, which is known to depend on hippocampal function. We also
      explored whether phenytoin could protect long-term potentiation (LTP) in
      hippocampal CA1 region from depression of chronic stressed rats. Isolated
      hippocampal slices of rats were used to observe the changes of LTP in hippocampal
      CA1 field with electrophysiological technique. The results showed that the motor
      activity of chronic forced-swimming rats was markedly higher than that of control
      rats, and phenytoin could not affect this change. The performance of water maze
      spatial training indicated that chronic stress damages long-term memory but not
      short-term memory, and phenytoin could reverse this long-term memory deficit. The
      increases of LTP after HFS in control and stress-phenytoin groups were
      significantly greater than those in stress-saline group (P < 0.05). There were no
      significant differences between control group and stress-phenytoin group (P >
      0.05) and between control and control-phenytoin groups (P > 0.05). These findings
      provided the first evidence with behavioral and electrophysiological technique
      that phenytoin could reverse the hippocampal-dependent memory deficit and
      depression of LTP induced by chronic stress, which may be helpful for exploring
      the pathogenesis and improving the therapy of depression.

PMID- 16099352
TI  - Differential effects of practice on the executive processes used for truthful and
      deceptive responses: an event-related brain potential study.
AB  - Behavior and event-related potentials (ERP) were recorded while participants made
      truthful and deceptive responses about previously memorized words under three
      instructional conditions: consistent truthful, consistent deceptive, and random
      deceptive. To determine if practice affected the deception-related activity we
      reported previously [R. Johnson, Jr., J. Barnhardt, J. Zhu, The deceptive
      response: effects of response conflict and strategic monitoring on the late
      positive component and episodic memory-related brain activity. Biol. Psychol., 64
      (2003) 217-253; R. Johnson, Jr., J. Barnhardt, J. Zhu, The contribution of
      executive processes to deceptive responding. Neuropsychologia, 42 (2004) 878
      901], participants performed two blocks of 145 trials of each condition. In the
      consistent truthful condition, practice benefited performance as indicated by
      decreased reaction time (RT) and RT variability. In addition, practice increased
      P300 amplitude and decreased the amplitude of a medial frontal negativity (MFN),
      which is believed to index the use of response-monitoring processes. However, a
      different pattern of results obtained in the two deception conditions. Although
      practice decreased RTs by almost as much as in the consistent truthful condition,
      the extent to which deceptive response in both conditions were slower than those
      in the consistent truthful condition actually increased slightly. Hence, the
      component of RT reflecting processing of conflicting response information did not
      decrease. In accord with the RT results, MFN amplitudes in the consistent
      deceptive and random deceptive conditions were unaffected by practice, suggesting
      that the amount of executive processes required to make and/or monitor deceptive
      responses was undiminished by practice. Although P300 amplitude increased
      slightly in the consistent deceptive condition, there was no change in the random
      deceptive condition. Thus, a major finding here is that, unlike truthful
      responses, the conceptually driven response conflicts underlying deceptive
      responses appear to be as resistant to practice-induced changes as described
      previously for perceptually driven response conflicts.

PMID- 16099353
TI  - Asymmetry of evoked potential latency to speech sounds predicts the ear advantage
      in dichotic listening.
AB  - The functional organization of the human auditory cortex is still not well
      understood with respect to speech perception and language lateralization.
      Especially, there is comparatively little data available in the brain imaging
      literature focusing on the timing of phonetic processing. We recorded auditory
      evoked potentials (AEP) from 27 scalp and additional EOG channels in 12 healthy
      volunteers performing a free report dichotic listening task with simple speech
      sounds (CV syllables: [ba], [da], [ga], [pa], [ta], [ka]). ERP analysis employed
      independent components analysis (ICA) wavelet denoising for artifact reduction
      and improvement of the SNR. The main finding was a 15-ms shorter average latency
      of the N1-AEP recorded from the scalp approximately overlying the left
      supratemporal cortical plane compared to the N1-AEP over the homologous right
      side. Corresponding N1 amplitudes did not differ between these sites. The
      individual AEP latency differences significantly correlated with the ear
      advantage as an index of speech/language lateralization. The behaviorally
      relevant difference in N1 latency between the hemispheres indicates that an
      important key to understanding speech perception is to consider the functional
      implications of neuronal event timing.

PMID- 16099354
TI  - Practice makes two hemispheres almost perfect.
AB  - Some tasks produce a performance advantage for conditions that require the
      processing of stimuli in two visual fields compared to conditions where single
      hemifield processing is sufficient. This advantage, however, disappears with
      practice. Although no definitive evidence yet exists, there are several possible
      mechanisms that might lead to improved performance of within- compared to across
      hemisphere processing with practice. These include a shift from a more demanding,
      algorithmic strategy to a less demanding memory-retrieval strategy (e.g., [G.
      Logan, Toward an instance theory of automatisation. Psych. Rev. 95 (1988) 492
      527]), as discussed by Weissman and Compton [D.H. Weissman, R.J. Compton,
      Practice makes a hemisphere perfect: the advantage of interhemispheric
      recruitment is eliminated with practice. Laterality, 8 (4) (2003) 361-375],
      and/or a more generalised practice effect [K. Kirsner, C. Speelman, Skill
      acquisition and repetition priming: one principle, many processes? J. Exp.
      Psychol., Learn. Mem. Cogn., 22 (1996) 563-575]. Contrary to Weissman and Compton
      findings, our results suggest that although single-hemisphere performance
      improves with practice, bi-hemispheric performance also improves substantially.
      Furthermore, these effects do not appear to be due to a shift in strategy but
      rather due to a general practice effect.

PMID- 16099355
TI  - Neural impact of the semantic content of visual mental images and visual
      percepts.
AB  - The existence of hemispheric lateralization of visual mental imagery remains
      controversial. In light of the literature, we used fMRI to test whether
      processing of mental images of object drawings preferentially engages the left
      hemisphere to compared non-object drawings. An equivalent comparison was also
      made while participants actually perceived object and non-object drawings.
      Although these two conditions engaged both hemispheres, activation was
      significantly stronger in the left occipito-temporo-frontal network during mental
      inspection of object than of non-object drawings. This network was also activated
      when perception of object drawings was compared to that of non-object drawings.
      An interaction was nonetheless observed: this effect was stronger during imagery
      than during perception in the left inferior frontal and the left inferior
      temporal gyrus. Although the tasks subjects performed did not explicitly require
      semantic analysis, activation of this network probably reflected, at least in
      part, a semantic and possibly a verbal retrieval component when object drawings
      were processed. Mental imagery tasks elicited activation of early visual cortex
      at a lower level than perception tasks. In the context of the imagery debate,
      these findings indicate that, as previously suggested, figurative imagery could
      involve primary visual cortex and adjacent areas.

PMID- 16099356
TI  - Configural and analytical processing of familiar and unfamiliar objects.
AB  - Configural processing could develop for non-face visual objects as one becomes
      familiar with those objects through repeated exposure. To explore the role of
      familiarity in object recognition, we studied the effect of adaptation to a
      visual object (adapting stimulus) on the identification performance of other
      objects (test stimulus) while adapting and test stimuli were exactly the same,
      shared parts or were completely different. We used a subset of English alphabets
      (p, q, d and b) as familiar objects and an unfamiliar set of symbols constructed
      from same parts but with different configurations. Adaptation to a member of each
      set led to a lower identification performance for that object in a crowding
      paradigm. Adaptation to each member of the unfamiliar set resulted in decreased
      identification performance for the same object and those members of the set that
      shared parts with the adapting stimulus. But no such transfer of adaptation was
      observed for the familiar set. Our results support the notion that processing of
      object parts plays an important role in the recognition of unfamiliar objects
      while recognition of familiar objects is mainly based on configural processing
      mechanisms.

PMID- 16099357
TI  - On the role of attention for the processing of emotions in speech: sex
      differences revisited.
AB  - In a previous cross-modal priming study [A. Schirmer, A.S. Kotz, A.D. Friederici,
      Sex differentiates the role of emotional prosody during word processing, Cogn.
      Brain Res. 14 (2002) 228-233.], we found that women integrated emotional prosody
      and word valence earlier than men. Both sexes showed a smaller N400 in the event
      related potential to emotional words when these words were preceded by a sentence
      with congruous compared to incongruous emotional prosody. However, women showed
      this effect with a 200-ms interval between prime sentence and target word whereas
      men showed the effect with a 750-ms interval. The present study was designed to
      determine whether these sex differences prevail when attention is directed
      towards the emotional content of prosody and word meaning. To this end, we
      presented the same prime sentences and target words as in our previous study.
      Sentences were spoken with happy or sad prosody and followed by a congruous or
      incongruous emotional word or pseudoword. The interval between sentence offset
      and target onset was 200 ms. In addition to performing a lexical decision,
      participants were asked to decide whether or not a word matched the emotional
      prosody of the preceding sentence. The combined lexical and congruence judgment
      failed to reveal differences in emotional-prosodic priming between men and women.
      Both sexes showed smaller N400 amplitudes to emotionally congruent compared to
      incongruent words. This suggests that the presence of sex differences in
      emotional-prosodic priming depends on whether or not participants are instructed
      to take emotional prosody into account.

PMID- 16099358
TI  - Visual search in temporally segregated displays: converging operations in the
      study of the preview benefit.
AB  - Preview benefit is an attentional phenomenon that enables observers to
      selectively search through new information in the visual field. In a preview
      search task, objects are presented in two sets, separated by a time interval
      (preview interval), and with the second set (new objects) containing the target.
      Event-related brain potentials (ERPs) were used to investigate whether preview
      benefit occurs via maintenance of inhibition of the old objects during the
      preview interval. ERPs time-locked to a color probe indicated that the old
      objects were actively attended rather than inhibited during the preview interval.
      Follow-up behavioral experiments produced converging results. The results suggest
      that, although participants might be using inhibition at later stages of the
      preview interval, they are not maintaining inhibition on the old objects
      throughout most of the preview interval.

PMID- 16099359
TI  - Phonological oddballs in the focus of attention elicit a normal P3b in dyslexic
      adults.
AB  - Difficulties in phonological processing have been proposed to be the core symptom
      of developmental dyslexia. Phoneme awareness tasks have been shown to both index
      and predict individual reading ability. In a previous experiment, we observed
      that dyslexic adults fail to display a P3a modulation for phonological deviants
      within an alliterated word stream when concentrating primarily on a lexical
      decision task [Fosker and Thierry, 2004, Neurosci. Lett. 357, 171-174]. Here we
      recorded the P3b oddball response elicited by initial phonemes within streams of
      alliterated words and pseudo-words when participants focussed directly on
      detecting the oddball phonemes. Despite significant verbal screening test
      differences between dyslexic adults and controls, the error rates, reactions
      times, and main components (P2, N2, P3a, and P3b) were indistinguishable across
      groups. The only difference between groups was found in the N1 range, where
      dyslexic participants failed to show the modulations induced by phonological
      pairings (/b/-/p/ versus /r/-/g/) in controls. In light of previous P3a
      differences, these results suggest an important role for attention allocation in
      the manifestation of phonological deficits in developmental dyslexia.

PMID- 16099360
TI  - Finding needles in haystacks: symbolic resonance analysis of event-related
      potentials unveils different processing demands.
AB  - Previous ERP studies have found an N400-P600 pattern in sentences in which the
      number of arguments does not match the number of arguments that the verb can
      take. In the present study, we elaborate on this question by investigating
      whether the case of the mismatching object argument in German (accusative/direct
      object versus dative/indirect object) affects processing differently. In general,
      both types of mismatches elicited a biphasic N400-P600 response in the ERP.
      However, traditional voltage average analysis was unable to reveal differences
      between the two mismatching conditions, that is, between a mismatching accusative
      versus dative. Therefore, we employed a recently developed method on ERP data
      analysis, the symbolic resonance analysis (SRA), where EEG epochs are
      symbolically encoded in sequences of three symbols depending on a given
      parameter, the encoding threshold. We found a larger proportion of threshold
      crossing events with negative polarity in the N400 time window for a mismatching
      dative argument compared to a mismatching accusative argument. By contrast, the
      proportion of threshold crossing events with positive polarity was smaller for
      dative in the P600 time window. We argue that this difference is due to the
      phenomenon of "free dative" in German. This result also shows that the SRA
      provides a useful tool for revealing ERP differences that cannot be discovered
      using the traditional voltage average analysis.

PMID- 16099361
TI  - Age-related changes in neural activity associated with concurrent vowel
      segregation.
AB  - Older adults exhibit degraded speech comprehension in complex sound environments,
      which may be related to overall age-related declines in low-level sound
      segregation. This hypothesis was tested by measuring event-related potentials
      (ERPs) while listeners identified two different vowels presented simultaneously.
      Older adults were less accurate than young adults at identifying the two vowels,
      although both groups improved similarly with increasing fundamental frequency
      differences (Deltaf0) between vowels. Reaction time data showed that older adults
      took more time to process stimuli, especially those with smaller Deltaf0. A
      negative ERP wave indexing the automatic registration of Deltaf0 (the object
      related negativity) was reduced in older adults. In contrast, young and older
      adults showed a similar pattern of neural activity indexing attentive processing
      of Deltaf0. The results suggest that aging affects the ability to automatically
      segregate speech sounds.

PMID- 16099362
TI  - Semantic processing of unattended meaning is modulated by additional task load:
      evidence from electrophysiology.
AB  - Recently, we observed that the perception of word meaning, as measured with the
      N400 component of the event-related brain potential, is delayed but unimpaired by
      various additional tasks when the language task requires the processing of
      semantic properties of the word stimuli. In the present study, we assessed
      whether similar effects would be observed when the language task relates to
      acoustic rather than to semantic properties of the word stimuli. The N400 was
      elicited by synonymous and non-synonymous spoken noun pairs that were to be
      classified according to tone pitch. In a single task experiment, there was a
      small but clear synonymity effect in ERPs (N400), indicating the availability of
      word meaning to the semantic system. Additional processing load, imposed by an
      overlapping task, abolished N400 for all SOAs when stimulus-response assignments
      were incompatible. For compatible assignments, N400 amplitude was present but
      much attenuated at the longest SOA. We conclude that the availability of task
      irrelevant meaning is modulated by additional task load and decay in short-term
      memory.

PMID- 16099363
TI  - Hemispheric metacontrol and cerebral dominance in healthy individuals
      investigated by means of chimeric faces.
AB  - Cerebral dominance and hemispheric metacontrol were investigated by testing the
      ability of healthy participants to match chimeric, entire, or half faces
      presented tachistoscopically. The two hemi-faces compounding chimeric or entire
      stimuli were presented simultaneously or asynchronously at different exposure
      times. Participants did not consciously detect chimeric faces for simultaneous
      presentations lasting up to 40 ms. Interestingly, a 20 ms separation between each
      half-chimera was sufficient to induce detection of conflicts at a conscious
      level. Although the presence of chimeric faces was not consciously perceived,
      performance on chimeric faces was poorer than on entire- and half-faces stimuli,
      thus indicating an implicit processing of perceptual conflicts. Moreover, the
      precedence of hemispheric stimulation over-ruled the right hemisphere dominance
      for face processing, insofar as the hemisphere stimulated last appeared to
      influence the response. This dynamic reversal of cerebral dominance, however, was
      not caused by a shift in hemispheric specialization, since the level of
      performance always reflected the right hemisphere specialization for face
      recognition. Thus, the dissociation between hemispheric dominance and
      specialization found in the present study hints at the existence of hemispheric
      metacontrol in healthy individuals.

PMID- 16099364
TI  - Are semantic and syntactic cues inducing the same processes in the identification
      of word order?
AB  - The purpose of this study was to find a common pattern of event-related potential
      (ERP) fluctuations regardless of the type of information (either semantic or
      syntactic) determining the presence of a reversed word order. ERPs were recorded
      while subjects read Spanish transitive sentences in which either semantic or
      syntactic information determined the actual word order. On the one hand (semantic
      condition), the order could be reversed by using an inanimate noun in the first
      noun phrase (NP), together with a verb representing an action that cannot
      correspond to an inanimate entity. On the other hand (syntactic condition), word
      order could be manipulated depending on the presence of a preposition preceding
      the second NP, which confirms the preferred word order, or a determiner,
      conveying a reversed word order. Interestingly, the inanimate first noun elicited
      a frontal negativity, which could be interpreted as the detection of an initial
      difficulty for using that noun as the subject of the sentence. At the point of
      disambiguation in either condition, a late posterior positivity was observed. The
      P600/SPS might, therefore, be an indicator of the syntactic processing costs
      incurred by the variation of word order, reflecting phrase structure reallocation
      processes common to this operation regardless of the cue used.

PMID- 16099365
TI  - The Thatcher illusion seen by the brain: an event-related brain potentials study.
AB  - In "Thatcherized" faces, the eyes and mouth regions are turned upside-down. Only
      when presented upright they are perceived as severely distorted. Common theories
      explain this effect by the loss of configural information for inverted faces. We
      investigated neural correlates of Thatcherization using event related potentials
      (ERPs). Sixteen right-handed participants performed identity classifications on
      Thatcherized or original familiar faces, presented either for 34 ms or 200 ms at
      an orientation of either 0 degrees, 90 degrees or 180 degrees. For the occipito
      temporal N170, we found (1) strong non-linear effects of orientation and (2)
      interactions between Thatcherization and orientation: Thatcherization resulted in
      larger N170 for upright faces, but smaller N170 for inverted faces. The novel
      finding of N170 effects of Thatcherization in inverted faces suggests differences
      in the neural encoding of Thatcherized and original inverted faces, even though
      Thatcherization escapes subjective perception in inverted faces.

PMID- 16099366
TI  - Feature binding in perceptual priming and in episodic object recognition:
      evidence from event-related brain potentials.
AB  - It is argued that explicit remembering is based on so-called episodic tokens
      binding together all perceptual features of a visual object. In episodic
      recognition, these features are collectively reactivated. In support of this
      view, it has been shown that changing sensory features of a stimulus from study
      to test decreases subject's performance in an episodic recognition task, even
      though the changed features are irrelevant for the recognition judgment. On the
      other hand, repetition priming is unaffected by such manipulations of perceptual
      specificity. Implicit memory performance is therefore thought to depend on
      structural representations, so-called types, comprising only invariant perceptual
      features, but no exemplar-specific details. Event-related potentials (ERPs) in
      our study revealed electrophysiological evidence for the differential involvement
      of these perceptual memory traces in explicit and implicit memory tasks.
      Participants attended either a living-nonliving task or an episodic recognition
      task with visually presented objects. During test both groups of participants
      processed new objects and old objects, which were repeated either identically or
      in a mirror-reversed version. In the implicit task ERPs showed an
      occipitoparietal repetition effect, which was the same for identically repeated
      items and mirror reversals. In contrast, in the explicit task an early mid
      frontal old/new effect for identical but not for mirror-reversed old objects was
      observed indicating involuntary access to perceptual information during episodic
      retrieval. A later portion of the old/new effect solely differentiated both types
      of old items from new ones.

PMID- 16099367
TI  - A neurodynamic model of the attentional blink.
AB  - A brain-based neural model of attention is used to simulate results for the
      'attentional blink', observed when a subject is exposed to a rapid stream of
      stimuli and required to monitor for two successive targets in the stream. The
      'blink' occurs when the time between the first and second targets is 200-500 ms,
      when there is reduced accuracy for report of the second target. The model gives a
      qualitative explanation of the phenomenon, especially of how attention is
      bolstered, during the processing to report of a given stimulus, in order to
      defend reportable information from attack by distracters.

PMID- 16099368
TI  - fMRI evidence of word frequency and strength effects in recognition memory.
AB  - We used event-related fMRI to investigate the neural correlates of encoding
      strength and word frequency effects in recognition memory. At test, participants
      made Old/New decisions to intermixed low (LF) and high frequency (HF) words that
      had been presented once or twice at study and to new, unstudied words. The
      Old/New effect for all hits vs. correctly rejected unstudied words was associated
      with differential activity in multiple cortical regions, including the anterior
      medial temporal lobe (MTL), hippocampus, left lateral parietal cortex and
      anterior left inferior prefrontal cortex (LIPC). Items repeated at study had
      superior hit rates (HR) compared to items presented once and were associated with
      reduced activity in the right anterior MTL. By contrast, other regions that had
      shown conventional Old/New effects did not demonstrate modulation according to
      memory strength. A mirror effect for word frequency was demonstrated, with the LF
      word HR advantage associated with increased activity in the left lateral temporal
      cortex. However, none of the regions that had demonstrated Old/New item retrieval
      effects showed modulation according to word frequency. These findings are
      interpreted as supporting single-process memory models proposing a unitary
      strength-like memory signal and models attributing the LF word HR advantage to
      the greater lexico-semantic context-noise associated with HF words due to their
      being experienced in many pre-experimental contexts.

PMID- 16099369
TI  - The control of memory retrieval: insights from event-related potentials.
AB  - Effective performance on episodic retrieval tasks requires the ability to
      flexibly adapt to changing retrieval demands ('retrieval orientations'; [M.D.
      Rugg, E.L. Wilding, Retrieval processing and episodic memory, Trends Cogn. Sci. 4
      (2000) 108-115]). We used event-related potentials (ERP) to examine whether
      maintaining a specific retrieval orientation and changing flexibly between
      different retrieval demands are mediated by the same brain systems or whether
      dissociable aspects of cognitive control are involved. Sixteen participants
      performed two recognition memory tasks. One required mere old/new decisions for
      words (general task), whereas the other task required the additional retrieval of
      each word's study font typeface (specific task). Furthermore, the participants
      either were asked to perform the same task continuously or to switch between the
      two tasks after every second test word. ERPs elicited by correctly rejected new
      (unstudied) words were analyzed. This enabled us to examine the ERP correlates of
      having adapted and maintained a task instruction as required during continuous
      blocks and of flexibly changing between retrieval demands during alternating
      blocks. The ERP analysis revealed more positive-going ERP slow waves for
      alternating blocks than for continuous blocks over bilateral frontal recording
      sites. This effect started around 250 ms after the test word and extended for
      several hundred milliseconds. As it was present for trials requiring a switch to
      the other task or to stay on the same task between 500 and 750 ms and no
      differences between the latter two trial types were obtained, it can be assumed
      that it is more related to general coordination requirements in alternating
      blocks, rather than to the actual control required to switch the retrieval task
      set. In addition, contrasting ERPs for the two task types revealed more positive
      going ERP slow waves in the specific task than in the general task in the
      continuous blocks at lateral frontal recording sites between 250 and 700 ms.
      Together, these findings suggest that there are electrophysiologically
      dissociable aspects of cognitive control, namely for adapting and maintaining a
      retrieval orientation and for flexibly changing between varying retrieval
      demands.

PMID- 16099370
TI  - The effect of encoding manipulation on word-stem cued recall: an event-related
      potential study.
AB  - The purpose of the present study was to find out whether the neural correlates of
      explicit retrieval from episodic memory would vary according to conditions at
      encoding when the words were presented in separate study/test blocks. Event
      related potentials (ERPs) were recorded while participants performed a word-stem
      cued-recall task. Deeply (semantically) studied words were associated with higher
      levels of recall and faster response times than shallowly (lexically) studied
      words. Robust ERP old/new effects were observed for each encoding condition. They
      varied in magnitude, being largest in the semantic condition. As expected, scalp
      distributions also differed: for deeply studied words, the old/new effect
      resembled that found in previous ERP studies of word-stem cued-recall tasks
      (parietal and right frontal effects, between 400-800 and 800-1100 ms post
      stimulus), whereas for shallowly studied words, the parietal old/new effect was
      absent in the latter latency window. These results can be interpreted as
      reflecting access to different kinds of memory representation depending on the
      nature of the processing engaged during encoding. Furthermore, differences in the
      ERPs elicited by new items indicate that subjects adopted different processing
      strategies in the test blocks following each encoding condition.

PMID- 16099371
TI  - Four-month-old infants process own mother's voice faster than unfamiliar voices-
      electrical signs of sensitization in infant brain.
AB  - Four-month-old infants heard their own mother's voice and a voice of an
      unfamiliar female as "oddballs" in a stream of acoustic information. The neuronal
      processing from 50 to 500 ms (as evaluated with event-related brain potentials,
      ERPs) was expected to be obligatory and from 500 to 900 ms to include cognitive
      processing. There was a clear shift in the processing speed between the mother's
      and unfamiliar voices at around 350 ms. While earlier obligatory ERP components
      occurred at significantly shorter latency to the mother's voice, later endogenous
      components were significantly delayed relative to the unfamiliar voice. The
      amplitude differences between the experimental stimuli were clearest for the last
      ERP potential, which presumably includes largest cognitive component. The size of
      the potential was significantly lower for mother than for unfamiliar voice. The
      results suggest that the behaviorally well-documented mutual sensitization
      between infant and mother and the special importance of output from mother is
      seen as an enhanced arousal to mother's voice and as signs of a clear memory
      template for own mother's voice at very early age.

PMID- 16099372
TI  - Eyes are special but not for everyone: the case of autism.
AB  - Current research indicates that human gaze direction is a special cue for
      shifting attention for one of two reasons: (1) it reflects social desires and
      intentions and (2) its basic perceptual features usually correspond to important
      events in the environment. This study, conducted with individuals with autism and
      with age- and IQ-matched typically developing individuals, dissociates these two
      often-confounded explanations and demonstrates that eyes appear to be special for
      typically developing individuals because of their social power, whereas gaze
      effects are mediated by feature correspondence among persons with autism.

PMID- 16099373
TI  - Thinking on your back: solving anagrams faster when supine than when standing.
AB  - There is potentially less locus coeruleus-noradrenergic system activity when
      lying down than when standing, an effect expected to develop via a difference in
      baroreceptor load. Furthermore, there is evidence implying that locus coeruleus
      noradrenergic system activity impairs attempts to solve anagrams. Consistent with
      these ideas, we found that subjects solved anagrams significantly faster when
      supine than when standing. With anagrams characterized as insight problems, our
      finding suggests that insight may be influenced by body posture.

PMID- 16099374
TI  - Only spontaneous counterfactual thinking is impaired in patients with prefrontal
      cortex lesions.
AB  - Counterfactual thoughts (CFT) are mental simulations of what might have been if
      another behavior had been executed. They are pervasive in everyday life, help
      people learn from experience, modulate their emotional state, and contribute to
      decision-making and social functioning. To test the hypothesis that the
      prefrontal cortex (PFC) is involved in the generation, content, and use of CFT,
      we studied 18 patients with strictly prefrontal cortex lesions. Our results
      indicated that the PFC is crucial only for self-generated counterfactual
      reflections. We did not detect CFT generation differences based on lesion
      location within the PFC. CFT performance correlated positively with measures of
      attention, creativity, verbal skills, conscientiousness, and self-esteem and
      negatively with depression and dysexecutive symptoms. An impairment in
      counterfactual thinking may contribute to the lack of regret and insight often
      observed in patients with frontal lobe lesions.

PMID- 16099375
TI  - Transcriptional regulation at the chromatin level in the cardiovasculature
      through protein-protein interactions and chemical modifications.
AB  - Transcriptional regulation in eukaryotes requires an understanding of the
      regulation of the chromatin structure. Chromatin is the eukaryotic-specific
      packaging/compaction of DNA with nucleosomal histones. This present review
      discusses recent advancements made in the field of chromatin-associated
      transcriptional regulation and their implications to the cardiovasculature.

PMID- 16099376
TI  - Molecular signature analysis: using the myocardial transcriptome as a biomarker
      in cardiovascular disease.
AB  - With the emergence of microarray technology, it is now possible to simultaneously
      assess the expression of tens of thousands of gene transcripts, providing a
      resolution and precision of phenotypic characterization not previously possible.
      In the field of cardiomyopathy, microarray studies have largely focused on gene
      discovery, identifying differentially expressed genes characteristic of diverse
      disease states, through which novel genetic pathways and potential therapeutic
      targets may be elucidated. However, gene expression profiling may also be used to
      identify a pattern of genes (a molecular signature) that serves as a biomarker
      for clinically relevant parameters. One study thus far does demonstrate that a
      molecular signature can accurately identify etiology in cardiovascular disease,
      supporting ongoing efforts to incorporate expression-profiling-based biomarkers
      in determining prognosis and response to therapy in heart failure. Microarray
      research in cardiomyopathy is still in its earliest stages. Nevertheless, the
      ultimate potential application of transcriptome-based molecular signature
      analysis is individualization of the management of patients with heart failure,
      whereby a patient with a newly diagnosed cardiomyopathy could, through molecular
      signature analysis, be offered an accurate assessment of prognosis and how
      individualized medical therapy could affect his or her outcome.

PMID- 16099377
TI  - Hsp20 and its cardioprotection.
AB  - The small heat shock protein Hsp20, also referred to as P20/HspB6, is expressed
      in the brain, stomach, liver, lung, kidney, blood, smooth muscle, skeletal
      muscle, and cardiac tissue. Although Hsp20 is not heat-inducible, several
      cellular signaling pathways appear to regulate its biologic functions. In recent
      years, tremendous advances have been made in elucidating the significance of
      Hsp20 in smooth muscle and its potential benefits on coronary vasculature. Of
      interest, recent findings have demonstrated that sustained beta-adrenergic
      stimulation results in expression and phosphorylation of cardiac Hsp20. Moreover,
      Hsp20 overexpression enhances cardiac function and renders cardioprotection
      against beta-agonist-mediated apoptosis and ischemia/reperfusion injury ex vivo
      and in vivo. This article reviews the new findings on translocation of Hsp20 in
      response to various stimuli and the multiple cellular targets of Hsp20, with
      special emphasis on its protective effects in the heart.

PMID- 16099378
TI  - Local cytokine environments drive aneurysm formation in allografted aortas.
AB  - The mechanistic differences between the pathways that induce stenotic vs.
      aneurysmal manifestations of atherosclerosis remain unknown. In a murine aortic
      interposition graft model, T helper cell type 1 (Th1)- vs. Th2-slanted cytokine
      environments differentially affected the vascular pathology; specifically,
      blockade of interferon-gamma signaling and/or Th2-enriched environments induced
      aneurysm formation associated with elastic tissue fragmentation. A Th2 cytokine
      milieu was shown to increase selected matrix metalloproteinase (MMP) expression,
      and interleukin 4 stimulated macrophage production of elastolytic matrix
      metalloproteinase 12 in vitro. The new findings establish important regulatory
      roles for a Th1/Th2 cytokine balance in modulating matrix remodeling, and have
      important implications for the pathophysiology of abdominal aortic aneurysms as
      well as atherosclerosis.

PMID- 16099379
TI  - Remote control of A-band cardiac thin filaments by the I-Z-I protein network of
      cardiac sarcomeres.
AB  - A conventional view of the role of sarcomeric thin filaments in cardiac function
      is that they react with cross-bridges that translate them toward the center of
      the sarcomere in a reaction triggered by Ca(2+) and powered by ATP. However, thin
      filaments also engage in a complex network of protein-protein interactions in the
      Z-disc. Thus, in the modern context, understanding of what thin filaments do in
      the heart must take into account not only A-band regions that react with cross
      bridges, but also I-Z-I regions that rarely, if ever, react with cross-bridges
      and dwell near and within the Z-disc. To highlight these multiplex functions of
      the thin filament, I discuss the hypothesis that physical and chemical reactions
      at the interface of the thin filaments with Z-disc proteins control the docking
      and activity of kinases and phosphatases that control the levels of
      phosphorylation of thin filament regulatory proteins. Testing this hypothesis has
      taken on new significance with the identification of multisite phosphorylation of
      thin filament proteins as a critical element in the control of cardiac
      contraction and relaxation reserve and in maladaptive mechanisms in heart
      failure. Moreover, multiple mutations in Z-disc proteins that link to prevalent
      cardiomyopathies are likely to alter this remote control of A-band thin filament
      function.

PMID- 16099380
TI  - STAT3-mediated activation of myocardial capillary growth.
AB  - Proper perfusion and vessel integrity are key requisites for myocardial
      homeostasis. In this regard, myocardial angiogenesis occurs in physiologic and
      pathologic conditions. Failure in this process and the resulting deficient oxygen
      supply induce loss and degeneration of cardiomyocytes, atrophy, and interstitial
      fibrosis and are viewed as a primary cause of myocardial dysfunction and heart
      failure. In this review, signal transducer and activator of transcription 3
      (STAT3) is highlighted as a regulator of proangiogenic circuits promoting vessel
      formation in the adult heart under physiologic and pathophysiologic conditions.
      Specifically, STAT3 regulates proangiogenic vascular endothelial growth factor
      (VEGF) expression and activity in the postnatal heart and suppresses an
      antiangiogenic and profibrotic gene program by controlling autocrine and
      paracrine circuits. In addition, signaling through STAT3 represents a necessary
      survival pathway for cardiomyocytes and endothelial cells and seems to promote
      cytokine-mediated cardiac angiogenesis. In contrast, STAT3 seems not to be
      required for differentiation processes of embryonic or adult endothelial
      progenitor cells. In summary, the properly timed expression and activation of
      STAT3 play a critical role on cardiac angiogenesis and involve the subtle control
      of paracrine and autocrine mechanisms regulating angiogenic circuits and survival
      pathways of cardiomyocytes and endothelial cells.

PMID- 16099381
TI  - The role of high-density lipoprotein in inflammation.
AB  - High-density lipoprotein (HDL) appears to have evolved as part of the innate
      immune system, which in part uses an enhanced oxidative state as a nonspecific
      means of protecting against many pathogens. In the absence of acute or chronic
      inflammation, HDL is anti-inflammatory in mice, rabbits, and humans. However,
      with the onset of a systemic inflammatory state such as what occurs in
      atherosclerosis, HDL becomes pro-inflammatory, enhancing the inflammatory
      response. The major apolipoprotein of HDL is apoA-I, which may be altered by
      oxidative processes in patients with atherosclerosis. As a result, HDL from such
      patients is less efficient in promoting cellular cholesterol efflux. The ability
      of HDL to inhibit the inflammatory properties of oxidized phospholipids and low
      density lipoproteins is also significantly altered. In mice and monkeys, the
      administration of an apoA-I-mimetic peptide renders pro-inflammatory HDL anti
      inflammatory, improves HDL-mediated cellular cholesterol efflux; in mice, it
      dramatically inhibits atherosclerosis. Understanding the role of HDL in
      inflammation may lead to new diagnostic and therapeutic approaches to
      atherosclerosis and other inflammatory conditions.

PMID- 16099382
TI  - The internal transcribed spacer of nuclear ribosomal DNA in the gymnosperm
      Gnetum.
AB  - We analyze the structure of the internal transcribed spacers ITS1 and ITS2 of the
      nuclear ribosomal DNA in the gymnosperm Gnetum, using a phylogenetic framework
      derived mainly from an intron in the nuclear low-copy LEAFY gene. Gnetum
      comprises 25-35 species in South America, Africa, and Asia, of which we sampled
      16, each with two to six clones. Criteria used to assess ITS functionality were
      highly divergent nucleotide substitution, GC content, secondary structure, and
      incongruent phylogenetic placement of presumed paralogs. The length of ITS1
      ranged from 225 to 986 bp and that of ITS2 from 259 to 305 bp, the largest ranges
      so far reported from seed plants. Gnetum ITS1 contains two informative sequence
      motifs, but different from other gymnosperms, there are only few and short (7-13
      bp) tandem repeats. Gnetum ITS2 contains two structural motifs, modified in
      different clades by shortening of stems and loops. Conspecific sequences grouped
      together except for two recombinant pseudogenes that had ITS1 of one clade and
      ITS2 of another. Most of the pseudogenic ITS copies, paralogs, and putative
      chimeras occurred in a clade that according to a fossil-calibrated chloroplast
      DNA clock has an age of a few million years. Based on morphology and chromosome
      numbers, the most plausible causes of the observed high levels of ITS
      polymorphism are hybridization, allopolyploidy, and introgression.

PMID- 16099383
TI  - Evolutionary history, population genetics, and gene flow in the common rosefinch
      (Carpodacus erythrinus).
AB  - We analyzed sequences of two mitochondrial DNA gene regions (control region and
      ND2) from 186 specimens obtained from 17 Eurasian localities covering most of the
      distribution of the common rosefinch to assess phylogeographic structure.
      Populations possessed a high level of nucleotide diversity relative to many other
      Palearctic species, suggesting that rosefinch populations are relatively old and
      possess high effective sizes. Mismatch distributions suggested that many
      localities experienced past population expansions, which are older than those
      expected for post-Pleistocene climate warming and reforestation of Eurasia. Our
      Phi(st) analysis revealed that 12.4% of total genetic variation was distributed
      among localities owing in part to the existence of three incompletely isolated
      groups: southwestern (subspecies C. e. kubanensis), northeastern (subspecies C.
      e. grebnitskii), and northwestern (subspecies C. e. erythrinus and C. e.
      ferghanensis). The three groups are not reciprocally monophyletic which suggests
      that they were formed relatively recently. Gene flow among groups is restricted.
      Coalescence analysis indicated dispersal asymmetry.

PMID- 16099384
TI  - The evolution of the spindlin gene in birds: sequence analysis of an intron of
      the spindlin W and Z gene reveals four major divisions of the Psittaciformes.
AB  - The Psittaciformes (parrots, parakeets) are among the most widely held captive
      birds. Yet, their evolution and their phylogenetic relationships have been
      relatively little studied. This paper describes the phylogenetic relationships
      between a number of Psittaciformes as derived from the sequences of the third
      intron of the Z-chromosomal and W-chromosomal spindlin genes. The Z-chromosomal
      sequences of the kakapo (Strigops habroptilus), the kea (Nestor notabilis), and
      the kaka (Nestor meridionalis) from New Zealand form a cluster which is the
      sister group to all other Psittaciformes. The results show further that the Z
      chromosomal sequences of the other species can be divided into two groups based
      on the occurrence of a sequence element ACCCT. The group with the insert (A) is
      mainly from species with an Australasian geographical distribution and includes
      such species as the Lories (Lorius, etc.), the budgerigar (Melospittacus
      undulatus), and the rosellas (Platycercus). It also includes the African
      lovebirds (Agapornidae), which are the only representative of group A outside
      Australasia. Group B, without the insert, includes the neotropical parrots and
      parakeets such as the amazons (Amazona, etc.), the macaws (Ara, etc.), and the
      conures (Aratinga, etc.), the Australian Cacatuini and the African species such
      as the African grey parrot (Psittacus erithacus) as well as Coracopsis vasa from
      Madagascar and Psittrichas fulgidus from New Guinea. The W-chromosomal sequence
      data show that another division of the Psittacidae is found in the replacement of
      a pyrimidine-rich segment occurring in many non-psittacines as well as the kakapo
      (S. habroptilus), the kea (N. notabilis), the kaka (N. meridionalis), and the
      Cacatuini by a microsatellite consisting of a variable number of TATTA monomers
      in the other Psittaciformes. The results support a Gondwanan origin of the
      Psittaciformes and the suggestion that paleogeographic events were a major force
      in psittacine divergence.

PMID- 16099385
TI  - The dawn of lipidomics.

PMID- 16099386
TI  - Mediator lipidomics.
AB  - Lipidomics the systematic decoding of lipid-based information in biosystems is
      comprised of identification and profiling of lipids and lipid-derived mediators.
      As practiced today, lipidomics can be subdivided into architecture/membrane
      lipidomics and mediator-lipidomics. The mapping of structural components and
      their relation to cell activation as well as generation of potent lipid mediators
      and networks involves a mass spectrometry-computational approach to appreciate
      inter-relationships and complex mediator networks important for cell homeostasis.
      Cell membranes are composed of a bilayer that contains phospholipids, fatty
      acids, integral membrane proteins, and membrane associated proteins,
      sphingolipids, etc. Membrane composition of many cell types is established.
      However, their organization and how they affect cell function remains an area of
      interest and a quest for lipidomics. Membranes serve barrier functions separating
      the inside from outside or compartments within cells, regulating passage of
      nutrients, gasses, and specific ions as well as generate signals to the
      intracellular milieu by the membrane's ability to interact with key proteins. The
      nature of these interactions and decoding the structure-function information
      within their organization is the promise of lipidomics (A-C). Metabolism of fatty
      acids is also an important energy source; hence, catabolism breakdown of fatty
      acids, areas of metabolomics that link to the signaling pathways, and roles of
      lipid mediators discussed herein.

PMID- 16099387
TI  - Sphingosine kinases, sphingosine-1-phosphate and sphingolipidomics.
AB  - It has become abundantly clear over the past decade that sphingolipids and their
      metabolites are key signaling molecules. Ceramide, the backbone of all
      sphingolipids, predominantly inhibits cell growth and induces apoptosis, while
      its metabolite, sphingosine-1-phosphate promotes growth and survival. Given the
      interconvertibility of these two opposing signaling molecules, it is essential
      that any study that examines the effects of one also look at the other. The newly
      available technology of liquid chromatography-tandem mass spectroscopy (LC-MS/MS)
      is increasingly being applied for this purpose, as it can quickly identify and
      measure many different sphingolipids simultaneously. An added benefit of LC-MS/MS
      is that it is several orders of magnitude more sensitive than enzymatic methods
      or more traditional chromatographic techniques, allowing smaller sample sizes and
      increased throughput. Here, we briefly discuss the importance of LC-MS/MS for
      measuring sphingolipid metabolites and some future directions researchers may
      take given the increasingly accessibility to this technology.

PMID- 16099388
TI  - The challenge of brain lipidomics.
AB  - After many years backstage, lipids have made a come back in the limelight of
      neuroscience. This renewed excitement was sparked by a series of convergent
      discoveries in the fields of neural development, synaptic physiology and receptor
      pharmacology, which have begun to reveal the roles played by lipid messengers and
      their receptors in brain function. Such roles extend from the development of the
      neocortex to the processing of complex behaviors, encompassing a territory as
      vast as those traditionally assigned to growth factors, neurotransmitters and
      neuropeptides. Along with these basic discoveries, technical advances have
      simplified the identification and quantification of neural lipids, achieving a
      degree of sensitivity and selectivity that was unthinkable only 10 years ago.
      Thanks to this progress, we can now resolve complex mixtures of lipid molecules
      and quantify each of their components, which are often present in tissues at
      vanishingly low concentrations. In this review, I outline several key features of
      brain lipid signaling and discuss the opportunities and challenges that such
      features impose on future lipidomic approaches.

PMID- 16099389
TI  - Targeted lipidomics: fatty acid amides and pain modulation.
AB  - Mass spectrometric approaches to the identification and quantification of lipid
      signalling molecules are reviewed. Fatty acid amides are an important new class
      of lipid signalling molecules which include oleamide, the endocannabinoid
      anandamide, the endovanilloid/endocannabinoid N-arachidonoyldopamine (NADA) and
      the endovanilloid N-oleoyldopamine (OLDA) among many others. This diverse group
      of endogenous compounds comprises combinations of acyl backbones coupled by an
      amide bond to any of a variety of different small polar molecules such as
      ethanolamine, various amino acids, and catecholamines. Many fatty acid amides
      appear to play a role in pain and inflammation. Targeted lipidomics of fatty acid
      amides aims to identify new members of this diverse class of compounds, of which
      only a few representative molecules have been characterized to date. This effort
      has been made feasible by advances in chromatography and mass spectrometry, which
      permits: (1) identification of compounds present in complex mixtures, (2)
      astronomical increases in sensitivity due to miniaturization of HPLC components,
      and (3) novel scanning modes that permit the identification of compounds
      exhibiting similar structural components. Insofar as lipid signalling molecules
      such as prostanoids, leukotrienes and endocannabinoids operate via G-protein
      coupled receptors (GPCR), it appears likely that many of the numerous lipids
      awaiting identification may serve as ligands for any of the greater than 150
      orphan GPCRs.

PMID- 16099390
TI  - Lysophospholipids in the nervous system.
AB  - This piece offers perspectives on the emerging roles of lysophospholipids, which
      include lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), for the
      biology and pathophysiology of the nervous system. It reflects opinions generated
      during a meeting sponsored by the National Institute on Drug Abuse (NIDA)
      entitled "Targeted Lipidomics: Signaling Lipids and Drugs of Abuse" held in
      Washington, D.C., 15-17 April 2004, organized by Dr. Rao Rapaka.
      Lysophospholipids represent one class of lipids that has many important actions
      mediated by G protein-coupled receptors. While influencing a large number of
      biologically important systems, this discussion will focus on the nervous system,
      including areas of future research.

PMID- 16099391
TI  - Functional lipidomics: the roles of specialized lipids and lipid-protein
      interactions in modulating neuronal function.
AB  - Lipids fulfill multiple specialized roles in neuronal function. In brain, the
      conduction of electrical impulses, synaptic function, and complex signaling
      pathways depend on the temporally and spatially coordinated interactions of
      specialized lipids (e.g., arachidonic acid and plasmalogens), proteins (e.g., ion
      channels, phospholipases and cyclooxygenases) and integrative lipid-protein
      interactions. Recent technical advances in mass spectrometry have allowed
      unparalled insight into the roles of lipids in neuronal function. Through shotgun
      lipidomics and multidimensional mass spectrometry, in conjunction with the
      identification of new classes of phospholipases (e.g., calcium dependent and
      calcium independent intracellular phospholipases), new roles for lipids in
      cerebral function have been accrued. This review summarizes the advances in our
      understanding of the types of lipids and phospholipases in the brain and the role
      of functional lipidomics in increasing our chemical understanding of complex
      neuronal processes.

PMID- 16099393
TI  - CD36 expression and brain function: does CD36 deficiency impact learning ability?
AB  - This article first presents an overview of published literature documenting the
      role of the scavenger receptor CD36 in activation of brain microglia with
      reference to brain pathologies such as Alzheimer's and malaria. Second, the
      possibility that CD36 may play a role in brain FA metabolism is discussed. Long
      chain polyunsaturated fatty acids (PUFAs) are important for brain function and
      are mostly derived from the plasma. Based on its role in facilitating FA uptake
      in several tissues and cell types, CD36 expressed on microvascular endothelial
      cells in the brain may facilitate local uptake of PUFAs. Alternatively, CD36 may
      influence brain FA supply indirectly via impacting utilization of dietary FA or
      their metabolism in tissues such as the liver. We examined the possibility that
      CD36 expression impacts brain function by evaluating the behavior of CD36 null
      mice using a battery of standard tests. Our data indicate that CD36 deficient
      mice have normal patterns of activity, anxiety and exploration of novel
      environments. However they appear to have a significant impairment in learning
      ability. These findings could provide a new perspective regarding the regulation
      of brain lipid metabolism.

PMID- 16099392
TI  - Lipid signaling: sleep, synaptic plasticity, and neuroprotection.
AB  - Increasing evidence indicates that bioactive lipids participate in the regulation
      of synaptic function and dysfunction. We have demonstrated that signaling
      mediated by platelet-activating factor (PAF) and cyclooxygenase (COX)-2
      synthesized PGE2 is involved in synaptic plasticity, memory, and neuronal
      protection [Clark GD, Happel LT, Zorumski CF, Bazan NG. Enhancement of
      hippocampal excitatory synaptic transmission by platelet-activating factor.
      Neuron 1992; 9:1211; Kato K, Clark GD, Bazan NG, Zorumski CF. Platelet-activating
      factor as a potential retrograde messenger in CA1 hippocampal long-term
      potentiation. Nature 1994; 367:175; Izquierdo I, Fin C, Schmitz PK, et al. Memory
      enhancement by intrahippocampal, intraamygdala or intraentorhinal infusion of
      platelet-activating factor measured in an inhibitory avoidance. Proc Natl Acad
      Sci USA 1995; 92:5047; Chen C, Magee CJ, Bazan NG. Cyclooxygenase-2 regulates
      prostaglandin E2 signaling in hippocampal long-term synaptic plasticity. J
      Neurophysiol 2002; 87:2851]. Recently, we found that prolonged continuous
      wakefulness (primarily rapid eye movement (REM)-sleep deprivation, SD) causes
      impairments in hippocampal long-term synaptic plasticity and hippocampus
      dependent memory formation [McDermott CM, LaHoste GJ, Chen C, Musto A, Bazan NG,
      Magee JC. Sleep deprivation causes behavioral, synaptic, and membrane
      excitability alterations in hippocampal neurons. J Neurosci 2003; 23:9687]. To
      explore the mechanisms underlying SD-induced impairments, we have studied several
      bioactive lipids in the hippocampus following SD. It appears that SD causes
      increases in prostaglandin D2 (PGD2) and 2-arachidonylglycerol (2-AG), and a
      decrease in PGE2, suggesting that these lipid messengers participate in memory
      consolidation during REM sleep. We have also explored the formation of endogenous
      neuroprotective lipids. Toward this aim, we have used ischemia-reperfusion damage
      and LC-PDA-ESI-MS-MS-based lipidomic analysis and identified docosanoids derived
      from synaptic phospholipid-enriched docosahexaenoic acid. Some of the docosanoids
      exert potent neuroprotective bioactivity [Marcheselli VL, Hong S, Lukiw WJ, et
      al. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte
      infiltration and pro-inflammatory gene expression. J Biol Chem 2003; 278:43807;
      Mukherjee PK, Marcheselli VL, Serhan CN, Bazan, NG. Neuroprotectin D1: A
      docosahexaenoic acid-derived docosatriene protects human retinal pigment
      epithelial cells from oxidative stress. Proc Nat Acad Sci USA 2004; 101:8491).
      Taken together, these observations that signaling lipids participate in synaptic
      plasticity, cognition, and survival indicate that lipid signaling is closely
      associated with several functions (e.g; learning and memory, sleep, and
      experimental stroke) and pathologic events. Alterations in endogenous signaling
      lipids or their receptors resulting from drug abuse lead to changes in synaptic
      circuitry and induce profound effects on these important functions. In the
      present article, we will briefly review bioactive lipids involved in sleep,
      synaptic transmission and plasticity, and neuroprotection, focusing mainly on our
      experimental studies and how these signaling molecules are related to functions
      and implicated in some neurologic disorders.

PMID- 16099394
TI  - Lipid signaling in embryo implantation.
AB  - A reciprocal interaction between the implantation-competent blastocyst and the
      receptive uterus is required for successful implantation. Although various
      molecular pathways are known to participate in this cross-talk, a comprehensive
      understanding of the implantation process is still missing. Gene expression
      studies and genetically engineered mouse models have provided evidence that lipid
      mediators serve as important signaling molecules in coordinating the series of
      events during early pregnancy including preimplantation embryo formation and
      development, implantation and postimplantation growth. This review focuses on the
      roles of two groups of lipid mediators, prostaglandins (PGs) and
      endocannabinoids, during early pregnancy. Our laboratory has shown that while PGs
      generated by the cPLA2-cyclooxygenase (COX) system are essential to ovulation,
      fertilization, and implantation, endocannabinoids are important for synchronizing
      preimplantation embryo development with uterine receptivity for implantation. A
      better understanding of these molecular signaling pathways is hoped to generate
      new strategies to correct implantation failure and improve pregnancy rates in
      women.

PMID- 16099395
TI  - Lipids and two-pore domain K+ channels in excitable cells.
AB  - Two-pore domain potassium channels (2PK) make up the newest branch of the
      potassium channel super-family. The channels are time- and voltage-independent
      and carry leak or "background" currents that are regulated by many different
      signaling molecules. These currents play an important role in setting the resting
      membrane potential and excitability of excitable cells, and, as a consequence,
      modulation of 2PK channel activity is thought to underlie the function of
      physiological processes as diverse as the sedation of anesthesia, regulation of
      normal cardiac rhythm and synaptic plasticity associated with simple forms of
      learning. Lipids, including arachidonate and its lipoxygenase metabolites,
      platelet-activating factor and anandamide have been identified as important
      mediators of some 2PK channels. Regulation can be effected by several different
      mechanisms. Some channels are regulated by G-protein-coupled receptors using well
      described signaling pathways that terminate in the activation of protein kinase
      C, whereas others are modulated by the direct interaction of the lipid with the
      channel.

PMID- 16099396
TI  - Anandamide as an intracellular messenger regulating ion channel activity.
AB  - The endocannabinoid anandamide (N-arachidonoylethanolamine) was proposed to be an
      extracellular retrograde messenger, which regulates excitability of neurons by
      cannabinoid CB1 receptor-dependent inhibition of neurotransmitter release. Recent
      findings indicate that the neuromodulatory actions of anandamide might be more
      complex. Anandamide has been shown to directly modulate various ion channels,
      such as alpha7-nicotinic acetylcholine receptors, T-type Ca2+ channels, voltage
      gated and background K+-channels and Transient Receptor Potential Vanilloid type
      1 (TRPV1) channels. The binding site of anandamide at some of these ion channels
      appears to be intracellular or at the bilayer interface. This rises the
      intriguing possibility that anandamide, prior to its release into the synaptic
      cleft, may regulate ion homeostasis and excitability of neurons as an
      intracellular modulator of ion channels independent of its action at cannabinoid
      CB1 receptors. This possibility might extend the concept of anandamide as an
      endocannabinoid retrograde messenger and may have profound implications for its
      role in neurotransmission and neuronal function. Here, we will review the
      evidence for this hypothesis.

PMID- 16099397
TI  - Lipid mediators regulating pain sensitivity.
AB  - The papers in this symposium demonstrate that lipid molecules are ubiquitous
      messengers that participate in intracellular signaling, function in intercellular
      communication, and serve as neurotransmitters. This review examines the
      contribution of lipid messengers in regulating a specific physiological function,
      the transmission of noxious sensory information (pain) in the nervous system.
      Lipid molecules play major roles in the modulation of pain sensitivity. Six types
      of lipid molecules (prostanoids, phosphatidyl inositol bisphosphate, ceramide,
      lipoxygenase metabolites of arachidonic acid, fatty acyl dopamines, and
      acylethanolamides) have been shown to modulate systems important in the
      regulation of pain responses. These molecules exert their actions by interacting
      with varied receptor systems. Evidence for their participation in the regulation
      of pain responses comes from in vitro demonstrations of their interactions with
      signaling systems known to be important in the regulation of pain sensitivity
      and, in some cases, from demonstration of their ability to modulate pain
      sensitivity after in vivo administration. One of these classes of lipid
      mediators, the acylethanolamides, inhibits pain responses, while the others
      appear to enhance pain sensitivity. Given the rapid growth in our understanding
      of lipidomics, evident in the papers of this issue, it is virtually certain that
      additional lipid mediators will be identified as being central to the regulation
      of pain responses.

PMID- 16099398
TI  - Mass spectrometry advances in lipidomica: collision-induced decomposition of Kdo2
      lipid A.
AB  - Mass spectrometry has made significant advances in the analysis of lipid
      substances, both simple and complex present in extracts of eukaryotic and
      prokaryotic cells. The development of the ionization techniques of electrospray
      ionization and matrix-assisted laser desorption ionization (MALDI) have both been
      applied to the analysis of lipids. The example of the types of structural
      information that can be obtained from MALDI-TOF tandem mass spectrometry is
      exemplified by the analysis of Kdo2-lipid A, a complex lipopolysaccharide known
      to activate toll-like 4 receptors on mammalian cells. Analysis of Kdo2-lipid A
      obtained from an Escherichia coli WBB06 was found to generate an abundant [M-H]-
      ion at m/z 2236.4 and a more abundant carbon-13 isotope at m/z 2237.4.
      Furthermore, collisional activation of the lipid A portion of the molecule at m/z
      1796.3 resulted in a series of ions corresponding to the loss of all four fatty
      acyl groups as neutral carboxylic acids. An altogether different challenge of
      mass spectrometry applied to the area of lipid analysis is that of quantitative
      analysis. Two rather different requirements have emerged. One with high precision
      and accuracy for the measurement of relatively few lipid species that are
      produced at very low concentrations and typically interact with specific receptor
      proteins. A rather different challenge is that for the analysis of abundant lipid
      classes, which are composed of multiple molecular species that can approach
      several hundred under certain circumstances.

PMID- 16099399
TI  - Targeted chiral lipidomics analysis.
AB  - Genomics, transcriptomics, and proteomics are proving to be very useful
      techniques, which have impacted significantly on our understanding mechanisms of
      human disease. However, this systems biology approach has several drawbacks than
      can be overcome by the integration of metabonomics and lipidomics. We have
      developed a targeted lipidomics approach that makes it possible to directly
      analyze chiral lipids generated in cellular systems. Bioactive lipids are usually
      present in trace amounts as enanatiomers and regioisomers that require separation
      before they can be analyzed by mass spectrometry. Normal phase chiral
      chromatography is generally used to resolve bioactive lipid enanatiomers.
      However, conventional electrospray and atmospheric pressure chemical
      ionization/tandem mass spectrometry have limited sensitivity when normal phase
      solvents are used, which makes it difficult to conduct studies when only trace
      amounts of the bioactive lipids are present. The use of electron capture
      atmospheric pressure chemical ionization/tandem mass spectrometry overcomes this
      problem. Enantiomers and regioisomers of targeted bioactive lipids can be
      quantified using stable isotope dilution methodology coupled with normal phase
      chiral chromatography and electron capture atmospheric chemical ionization/tandem
      mass spectrometry. A targeted lipidomics profile from rat epithelial cells
      transfected with cyclooxygenase-2 and maintained in culture was obtained.
      Inhibition with the non-selective cyclooxygenase inhibitor aspirin increased the
      formation of 15(R)-hydroxyeicosatetraenoic acid in the cells although it
      completely inhibited formation of the 15(S)-enantiomer and prostaglandin E2. New
      mass spectrometry instrumentation with an improved atmospheric pressure chemical
      ionization source was found to be an order of magnitude more sensitive than
      existing instruments for analysis of bioactive lipids using electron capture
      methodology. This type of mass spectrometer will permit a more detailed analysis
      of cellular bioactive lipid production than has been possible previously. It will
      also permit in vivo targeted lipidomics studies to be conducted using biological
      fluids derived from animal models and human subjects.

PMID- 16099400
TI  - Probing lipid-protein interactions using lipid microarrays.
AB  - Lipids are central to the regulation and control of several cellular functions.
      They form many of the important structural features of cells, and are critical
      members of cellular signal transduction pathways. Cellular dysfunction is often
      caused by errors in lipid signaling; therefore, the proteins that interact with,
      synthesize or metabolize the lipids are potential therapeutic targets.
      Characterizing the contingent of cellular lipids and their abundance and how this
      is associated with disease will facilitate understanding how to intervene to
      correct diseases caused by dysfunctional lipid signaling. Since lipid-signaling
      networks involve several classes of proteins it is essential to determine the
      identity and role of these proteins in order to understand the networks. These
      proteins may be receptors, effectors, transporters or enzymes. We present tools,
      specifically, a lipid microarray platform, to uncover lipid-binding effector
      proteins that function in lipid signaling pathways. Lipid microarrays will allow
      researchers to obtain a comparable fingerprint of the proteins from a cell or
      tissue that bind to lipids, and also enable the identification of functionally
      important lipid-binding proteins. By applying a systematic approach to the
      quantification of lipid-protein interactions, lipid microarrays will provide an
      integrated knowledge base for the human lipidome. These tools have the potential
      to identify and validate targets to improve personalized medicine and health.

PMID- 16099401
TI  - Visualization and perturbation of phosphoinositide and phospholipid signaling.
AB  - Cells signal through lipids that are produced by phospholipid (PL) and
      phosphoinositide (PIPn) metabolism involve three enzymatic processes: (i) ester
      and phosphodiester hydrolysis by phospholipases, (ii) monophosphate hydrolysis by
      phosphatases, and (iii) phosphorylation of hydroxy groups by kinases. Unregulated
      enzyme activity correlates with specific pathologies, which are specific targets
      for therapeutic intervention. A variety of reagents now permit monitoring of in
      vitro enzyme activity, spatiotemporal changes of intracellular lipid
      concentrations, and identification of lipid-protein interactions. This minireview
      summarizes a chemical biology approach that illustrates how chemically
      synthesized affinity probes can be used to characterize changes in lipid
      signaling in cellular and molecular biology.

PMID- 16099402
TI  - Chemical approaches to the lysophospholipid receptors.
AB  - Both ligand-based and GPCR privileged scaffold chemical tools have recently
      emerged to provide new insights into the function and physiology of the GPCR
      lysophospholipid receptors both in vitro and in vivo. Both rational, design-based
      approaches as well as hybrid approaches where high throughput screening has been
      coupled to an understanding of critical molecular interactions have been
      productive in advancing understanding of physiology and potential therapeutics in
      this field. It is now feasible to identify reasonably potent and selective small
      molecules that provide chemical proof-of-concept in vivo directly from high
      throughput screening. These developments, coupled with the availability of
      receptor knock-out mice, presage rapid progress in the field.

PMID- 16099403
TI  - In vivo approaches and rationale for quantifying kinetics and imaging brain lipid
      metabolic pathways.
AB  - Developing a kinetic strategy to examine rates of lipid metabolic pathways can
      help to elucidate the roles that lipids play in tissue function and structure in
      health and disease. This review summarizes such a strategy, and shows how it has
      been applied to quantify different kinetic aspects of brain lipid metabolism in
      animals and humans. Methods involve injecting intravenously a radioactive or
      heavy isotope labeled substrate that will be incorporated into a lipid metabolic
      pathway, and using chemical analytical and/or imaging procedures (e.g.,
      quantitative autoradiography or positron emission tomography) to determine tracer
      distribution in brain regions and their lipid compartments as a function of time.
      From the measurements, fluxes, turnover rates, half-lives and ATP consumption
      rates can be calculated, and incorporation rates can be imaged. Experimental
      changes in these kinetic parameters can help to identify changes in the
      expression of regulatory enzymes, and thus aid in drug targeting. Cases that are
      discussed are arachidonic acid turnover and imaging of neuroreceptor-initiated
      phospholipase A2 activation, ether phospholipid biosynthesis, and kinetics of the
      phosphatidylinositol cycle.

PMID- 16099404
TI  - Genomic insights into mediator lipidomics.
AB  - G protein-coupled receptors (GPCR) are used ubiquitously and widely for signal
      transduction across the plasma membrane. The ligands for GPCRs are structurally
      diverse and include peptides, odorants, photon, ions and lipids. It is thought
      that GPCRs evolved by gene duplication and mutational events that diversified the
      ligand binding and signaling properties, thereby resulting in paralogues in
      various organisms. Genomic sequencing efforts of various organisms indicate that
      GPCRs evolved very early in evolution; for example, unicellular eukaryotes use
      GPCRs for mating, differentiation and sporulation responses and prokarotes
      utilize these receptors for phototransduction, as exemplified by the
      bacteriorhodopsin, a photon sensor. Many GPCRs fall into subfamilies, usually
      determined by structural similarity to their ligands. Bioactive lipids such as
      lysophospholipids, eicosanoids, ether lipids and endocannabinoids, which are
      produced widely in evolution, also signal through GPCRs. Thus, distinct
      subfamilies of bioactive lipid GPCRs, such as prostanoid receptors,
      lysophosphatidic, sphingosine 1-phosphate, leukotrienes, hydroxy fatty acids,
      endocannabinoids and ether lipids exist in the mammalian genome. With the
      increasing availability of genomic information throughout the phylogenetic tree,
      orthologues of bioactive lipid receptors are found in the genomes of vertebrates
      and chordates but not in worms, flies or other lower organisms. This is in
      contrast to GPCRs for biogenic amines and polypeptide growth factors, which are
      conserved in invertebrates as well. Thus, it appears that with the evolution of
      chordates, lipids may have acquired novel roles in cell-cell communication events
      via GPCRs. This hypothesis will be discussed using the prostanoid and
      lysophospholipid signaling systems. Since such bioactive lipids play critical
      roles in immune, vascular and nervous systems, this suggests that lipid
      metabolite signaling via the GPCRs co-evolved with the development of
      sophisticated vascular, immune and nervous systems in chordates and vertebrates.

PMID- 16099405
TI  - How lipophilic cannabinergic ligands reach their receptor sites.
AB  - It is postulated that lipophilic ligands reach their sites of action on membrane
      bound functional proteins through fast lateral diffusion across the membrane
      bilayer. We have shown using NMR experiments that such ligands when incorporated
      in a membrane system assume a preferred orientation and conformation. While
      occupying a specific location within the bilayer, these molecules undergo fast
      lateral diffusion which allows them to engage in productive interactions with
      their respective protein sites of action. The proposed model is discussed using a
      group of classical and non-classical cannabinoids as well as the endogenous
      cannabinoid ligand anandamide.

PMID- 16099406
TI  - Targeted lipidomics and drug abuse research.
AB  - Contemporaneously with genomics and proteomics technologies, lipidomics may be
      recognized as the next important emerging technology. The emergence of this
      important area of "omics" could very well mark the beginning of "the decade of
      the lipids." A workshop on lipidomics was held in Washington, DC, by the National
      Institute on Drug Abuse (NIDA) in April 2004. The goal of the workshop was to
      bring together scientists working at the frontier of lipid research, to discuss
      their findings in this area and to promote "lipidomics," in general, but also
      with a special focus on its application to drug abuse research and development of
      therapies to treat addiction.

PMID- 16099407
TI  - Targeted lipidomics: signaling lipids and drugs of abuse.

PMID- 16099408
TI  - Distinguishing phospholipase A2 types in biological samples by employing group
      specific assays in the presence of inhibitors.
AB  - This manuscript reviews and updates radiolabel-based enzyme assays designed to
      distinguish the activity of phospholipase A2 (PLA2) types in biological samples.
      This approach should be useful in lipidomics studies. The assays were originally
      designed to differentiate between Group IVA cytosolic PLA2 (GIVA cPLA2), Group
      VIA calcium-independent PLA2 (GVIA iPLA2), Group IIA secreted PLA2 (GIIA sPLA2)
      and Group V secreted PLA2 (GV sPLA2). The specificity of these assays has now
      been confirmed using purified, recombinant human PLA2s and the utility of these
      assays is demonstrated with rat spinal cord homogenate as an example of a
      biological tissue sample of interest to the neuroscience community. Modifications
      to the original assays by the addition of group-specific inhibitors are presented
      to ensure the specificity of the assays and to further differentiate between
      recently identified PLA2s. Specific tests are suggested to confirm the
      specificity of each assay. Additionally, it was discovered that one commonly used
      GIVA cPLA2/GVIA iPLA2 inhibitor, methyl arachidonyl fluorophosphonate (MAFP) from
      one commercial source, was found to inhibit GIIA sPLA2 and GV sPLA2, but not GIVA
      cPLA2, presumably due to oxidation of the compound during shipment, resulting in
      a different molecule with altered specificity.

PMID- 16099409
TI  - AAV8-mediated hepatic expression of acid sphingomyelinase corrects the metabolic
      defect in the visceral organs of a mouse model of Niemann-Pick disease.
AB  - Acid sphingomyelinase deficiency is a lysosomal storage disorder in which the
      defective lysosomal hydrolase fails to degrade sphingomyelin. The resulting
      accumulation of substrate in the lysosomes of histiocytic cells leads to
      hepatosplenomegaly and severe pulmonary inflammation. Administration of a
      recombinant AAV1 vector encoding human acid sphingomyelinase to acid
      sphingomyelinase knockout (ASMKO) mice effectively reduced the accumulated
      substrate in all of the affected visceral organs. However, more complete and
      rapid clearance of sphingomyelin was observed when an AAV8-based serotype vector
      was used in lieu of AAV1. Importantly, AAV8-mediated hepatic expression of higher
      and sustained levels of the enzyme also corrected the abnormal cellularity, cell
      differentials, and levels of the chemokine MIP-1alpha in the bronchoalveolar
      lavage fluids of the ASMKO mice. Treatment also reversed the morphological
      aberrations associated with the alveolar macrophages of ASMKO mice and restored
      their phagocytic activity. No antibodies to the expressed enzyme were detected
      when the viral vectors were used in conjunction with a transcription cassette
      harboring a liver-restricted enhancer/promoter. Together, these data support the
      continued development of AAV8-mediated hepatic gene transfer as an approach to
      treat the visceral manifestations observed in individuals with acid
      sphingomyelinase deficiency.

PMID- 16099410
TI  - Phenotypic improvement of dystrophic muscles by rAAV/microdystrophin vectors is
      augmented by Igf1 codelivery.
AB  - The absence of dystrophin in Duchenne muscular dystrophy (DMD) leads to
      sarcolemmal instability and enhances the susceptibility of muscle fibers to
      contraction-induced injury. Various viral vectors have been used to deliver mini-
      and microdystrophin expression cassettes to muscles of dystrophin-deficient mdx
      mice, significantly increasing both the morphological and the functional
      properties of the muscles. However, dystrophin delivery to adult mdx mice has not
      yielded a complete rescue of the dystrophic phenotype. Here we investigated a
      novel strategy involving dual gene transfer of recombinant adeno-associated viral
      vectors expressing either microdystrophin (rAAV-muDys) or a muscle-specific
      isoform of Igf-1 (rAAV-mIgf-1). Injection of mdx muscles with rAAV-muDys reduced
      myofiber degeneration and turnover and increased their resistance to mechanical
      injury, but did not increase muscle mass or force generation. Injection of mdx
      muscles with rAAV-mIgf-1 led to increased muscle mass, but did not provide
      protection against mechanical injury or halt myofiber degeneration, leading to
      loss of the vector over time. In contrast, co-injection of the rAAV-muDys and
      rAAV-mIgf-1 vectors resulted in increased muscle mass and strength, reduced
      myofiber degeneration, and increased protection against contraction-induced
      injury. These results suggest that a dual-gene, combinatorial strategy could
      enhance the efficacy of gene therapy of DMD.

PMID- 16099411
TI  - Factors influencing adenovirus-mediated airway transduction in fetal mice.
AB  - Intra-amniotic injection of adenovirus allows transduction of the fetal airways
      following natural fetal breathing movements. This administration method is
      promising for use in gene therapy for cystic fibrosis and other diseases for
      which the main target for exogenous gene expression is the lung. Here we have
      investigated factors that may affect the efficacy of gene transfer to the murine
      fetal lung. We examined marker compound distribution and transgene expression
      (from a first-generation adenoviral vector) at different stages of development.
      This demonstrated that fetal breathing movements at 15-16 days of gestation are
      of sufficient intensity to carry marker/vector into the fetal lungs. These
      movements can be significantly stimulated by the combination of intra-amniotic
      theophylline administration and postoperative exposure of the dam to elevated
      CO(2) levels. However, the most important factor for efficient and consistent
      pulmonary transgene delivery is the dose of adenoviral vector used, as both the
      degree of transduction and the percentage of lungs transduced increases with
      escalating viral dose.

PMID- 16099412
TI  - Aerosolized nanogram quantities of plasmid DNA mediate highly efficient gene
      delivery to mouse airway epithelium.
AB  - The lung is an important target of gene therapeutic interventions. In contrast to
      intratracheal instillation, inhalation would be the most practical route of
      administration in clinical applications. Here we show that aerosolized nanogram
      quantities of pDNA complexed to PEI (350 ng) yielded transfection levels 15-fold
      higher than a 140-fold higher dose (50 microg) of the same vector applied
      directly to the lungs of mice via intratracheal intubation. An important efficacy
      parameter is the osmolarity of the aerosol and not biophysical properties of the
      nebulized vector. Vectors formulated and nebulized in hypoosmotic distilled water
      yielded 57- and 185-fold higher expression levels than those in isotonic 5%
      glucose or Hepes-buffered saline, respectively. Pretreatment of mice with
      nebulized indomethacin, which prevents water-induced airway alteration, resulted
      in lower gene expression, whereas pretreatment with EGTA or polidocanol, which
      modulate tight-junction activity, had no effect. These results, together with
      histological analysis of regional lung deposition and gene expression, suggest
      that a temporary water-induced hypoosmotic shock permeabilizes the epithelium
      sufficiently to allow vector uptake. The so far observed inefficiency of nonviral
      gene delivery to the airways may be the result of an inappropriate method of
      vector administration.

PMID- 16099413
TI  - Targeting viral-mediated transduction to the lung airway epithelium with the anti
      inflammatory cationic lipid dexamethasone-spermine.
AB  - We formulated adenovirus (AdV) vectors with cationic steroid liposomes containing
      dexamethasone-spermine (DS)/dioleoylphosphatidylethanolamine (DOPE) in an effort
      to overcome the lack of apically expressed AdV vector receptors on airway
      epithelial cells and to reduce the inflammation associated with AdV vector
      exposure. An AdV vector (1 to 2.5 x 10(11) genome copies) expressing human
      placental alkaline phosphatase or beta-galactosidase (LacZ) was delivered alone
      or complexed with DS/DOPE, DC-Chol/DOPE, or dexamethasone to C57Bl/6 mice via
      intranasal instillation. Formulation of the AdV vector with DS/DOPE and DC
      Chol/DOPE resulted in transgene expression targeted only to the airway epithelial
      cells with minimal expression in alveolar cells, while AdV alone caused high
      alveolar transduction. The DS/DOPE and dexamethasone formulations greatly reduced
      cellular infiltrates compared to AdV vector alone, while formulation with DC
      Chol/DOPE did not. IFN-gamma was significantly elevated at day 7 in mice
      receiving only the AdV vector compared to the AdV vector formulated with DS/DOPE,
      DC-Chol/DOPE, or dexamethasone. Lipid formulation of adeno-associated virus
      vector expressing LacZ also produced airway epithelial targeting, similar to the
      AdV vector. Viral vectors can be formulated with DS/DOPE to improve targeting to
      the airway epithelium in vivo and to attenuate vector-induced inflammation
      through the pharmacological activity of DS.

PMID- 16099414
TI  - Evaluation of viral and mammalian promoters for use in gene delivery to salivary
      glands.
AB  - To optimize vectors for salivary gland gene transfer, we screened viral
      [cytomegalovirus (CMV; human immediate early), Rous sarcoma virus (RSV), simian
      virus 40, and Moloney murine leukemia virus long terminal repeat] and mammalian
      [elongation factor 1alpha (EF1alpha), cytokeratin 18 (K18), cytokeratin 19 (K19),
      kallikrein (Kall), and amylase (AMY), all human, and rat aquaporin-5 (rAQP5), and
      derivative elements] promoters driving luciferase activity in vitro and in vivo.
      In adenoviral vectors, the CMV promoter showed highest activity, with the
      EF1alpha and RSV promoters slightly less powerful, in rat submandibular glands
      (SMGs). The K18 2.5-kb, K19 3.0-kb, and rAQP5 0.4-kb and Kall promoters had
      intermediate activity, while the AMY promoter exhibited lowest activity. To
      localize transgene expression, enhanced green fluorescence protein was used. The
      CMV, RSV, EF1alpha, K18 2.5-kb, K19 3.0-kb, rAQP5 0.4-kb, and AMY promoters were
      not cell-type specific in SMGs; however, the Kall promoter was primarily active
      in ductal cells. These data will facilitate optimal expression cassette design
      for salivary gland gene transfer.

PMID- 16099415
TI  - Comparison of HIV- and EIAV-based vectors on their efficiency in transducing
      murine and human hematopoietic repopulating cells.
AB  - The use of lentiviral vectors for gene transfer into hematopoietic stem cells has
      raised considerable interest as these vectors can permanently integrate their
      genome into quiescent cells. Vectors based on alternative lentiviruses would
      theoretically be safer than HIV-1-based vectors and could also be used in HIV
      positive patients, minimizing the risk of generating replication-competent virus.
      Here we report the use of third-generation equine infectious anemia virus (EIAV)-
      and HIV-1-based vectors with minimal viral sequences and absence of accessory
      proteins. We have compared their efficiency in transducing mouse and human
      hematopoietic stem cells both in vitro and in vivo to that of a previously
      documented second-generation HIV-1 vector. The third-generation EIAV- and HIV
      based vectors gave comparable levels of transduction and transgene expression in
      both mouse and human NOD/SCID repopulating cells but were less efficient than the
      second-generation HIV-1 vector in human HSCs. For the EIAV vector this is
      possibly a reflection of the lower protein expression levels achieved in human
      cells, as vector copy number analysis revealed that this vector exhibited a trend
      to integrate equally efficiently compared to the third-generation HIV-1 vector in
      both mouse and human HSCs. Interestingly, the presence or absence of Tat in viral
      preparations did not influence the transduction efficiency of HIV-1 vectors in
      human HSCs.

PMID- 16099416
TI  - The use of recognition information and additional cues in inferences from memory.
AB  - Goldstein and Gigerenzer's (2002) "Recognition Heuristic" (RH) was tested for its
      empirical validity in an experimental paradigm with induced recognition of
      objects. RH claims that upon inferring which of two objects (e.g., cities) scores
      higher on a criterion (e.g., city size), a recognized object will be chosen over
      an unrecognized one, if the recognition is a valid predictor of the criterion
      without considering additional object information. Trying to avoid potential
      shortcomings of former studies, we (a) used the city population task, (b)
      provided additional cue information only for recognized cities, and (c) had
      participants draw inferences from memory. Participants learned city names and
      additional information about some cities. They also learned that recognition and
      the additional information were valid predictors of the criterion "city size". In
      a subsequent decision phase, the additional information about the cities in
      memory strongly affected the inferences, suggesting that recognition information
      is clearly integrated into judgments, but by no means in a non-compensatory
      fashion that would dominate every other cue.

PMID- 16099417
TI  - Thirty years of haemoglobin electrochemistry.
AB  - Electrochemical investigations of the blood oxygen carrier protein include both
      mediated and direct electron transfer. The reaction of haemoglobin (Hb) with
      typical mediators, e.g., ferricyanide, can be quantified by measuring the
      produced ferrocyanide which is equivalent to the Hb concentration. Immobilization
      of the mediator within the electrode body allows reagentless electrochemical
      measuring of Hb. On the other hand, entrapment of the protein within layers of
      polyelectrolytes, lipids, nanoparticles of clay or gold leads to a fast
      heterogeneous electron exchange of the partially denatured Hb.

PMID- 16099418
TI  - Monitoring "promiscuous" drug effects on single cells of multiple cell types.
AB  - Recent advances in genomics and molecular pathogenesis studies have determined
      that many diseases are caused by a multiplicity of factors. New drug regimens may
      consist of multiple biologically active agents designed to act synergistically on
      multiple biochemical targets. Live cell assays are becoming a standard for
      identifying new drug candidates with an emphasis on "homogeneous" living cell
      assays in which multiple cell lines are mixed and monitored simultaneously. In
      this study, we used a high-density single living cell array, based on an optical
      imaging fiber bundle microwell array, to simultaneously monitor "promiscuous"
      drug effects on single cells of multiple cell types. Such a capability allows for
      a more comprehensive understanding of how cells dynamically respond to
      combinatorial drug libraries or how different cellular pathways and regulation
      circuits respond cooperatively to drugs in individual cells.

PMID- 16099419
TI  - Influence of hand grenade weight, shape and diameter on performance and
      subjective handling properties in relations to ergonomic design considerations.
AB  - Three hand-grenade design factors, namely shape (ball, oval, can), diameter (55,
      60, and 65 mm) and weight (300, 400, and 500 g), were assessed. The objective
      criteria were (1) throwing distance from the grenade stop point to throwing
      point, and (2) error distance from the grenade stop point to the target. The
      subjective criteria were (3) the overall rating of handling (to hold and control)
      properties and (4) the rating of perceived exertions of throwing strength. Twenty
      ROC Army soldiers threw a Mark II practice grenade to familiarize them with the
      throwing procedure, and then, while standing, threw 21 experimental, mockup
      grenades at a target indicated by a flagpole 40 m away from the throwing point.
      Grenade weight had the greatest effect on both subjective and objective criteria.
      The 300 g grenade had the greatest throwing distance (38.6+/-6.5 m) and had the
      greatest accuracy (6.9+/-3.9 m). Grenade shape was also a significant influence
      based on both the subjective and objective criteria; with the ball shape being
      the best. Grenade diameter, within the range tested, did not affect either the
      subjective or objective criteria.

PMID- 16099420
TI  - The effect of speech recognition on working postures, productivity and the
      perception of user friendliness.
AB  - A comparative, experimental study with repeated measures has been conducted to
      evaluate the effect of the use of speech recognition on working postures,
      productivity and the perception of user friendliness. Fifteen subjects performed
      a standardised task, first with keyboard and mouse and, after a six week training
      period, with speech recognition. The use of speech recognition leads to improved
      postures of wrist, forearm, upper arm and shoulder and improvement of neck
      movements when compared to the use of keyboard and mouse. Although the
      observation method was basic, this study provides insight into the potential
      benefits speech recognition has for posture. However, productivity decreased for
      most subjects and speech recognition appears to be usable for specific tasks
      only. From the perspective of productivity and the perception of user
      friendliness further development of speech recognition software is necessary. Up
      to now, speech recognition seems especially beneficial for people with WMSD
      complaints.

PMID- 16099421
TI  - Effects of attentional direction, age, and coping style on cold-pressor pain in
      children.
AB  - This study assessed the relative efficacy of two imagery-based attentional
      strategies for modifying pain experience in children. Children aged 7-14 years (n
      = 120) were randomly assigned to one of three conditions: distraction, sensory
      focussing or control (no imagery). The distraction condition prompted children to
      focus their attention externally; the sensory-focussing condition prompted the
      child to focus internally on physical sensations. Self-report measures of pain
      coping style preferences and imagery ability were completed. Children's pain
      tolerance and perceptions of pain intensity were assessed using a 10 degrees C
      cold-pressor task. Results showed pain intensity ratings after 1 min were lower
      for both intervention conditions than for the controls. Younger children (7-9
      years) showed higher pain tolerance in the distraction condition than in the
      sensory-focussing condition, whereas both interventions were equally effective
      for older children (10-14 years). Among older children, coping style interacted
      with the intervention type: in the sensory-focussing condition, pain tolerance
      was negatively associated with self-reported distraction-based coping style,
      whereas in the distraction condition this association was positive. The results
      are interpreted with reference to current models of attention. The implications
      for use of attentional strategies in helping children to cope with clinical pain
      are discussed.

PMID- 16099422
TI  - Murine lipid phosphate phosphohydrolase-3 acts as a cell-associated integrin
      ligand.
AB  - Lipid phosphate phosphohydrolase-3 (LPP3) is a cell surface protein that exhibits
      ectoenzyme activity. Previously, we identified human LPP3 in a functional assay
      of angiogenesis and showed that the Arg-Gly-Asp (RGD) motif in the proposed
      second extracellular domain interacts with a subset of integrins to mediate cell
      cell adhesion. In contrast to the RGD domain of human LPP3, murine Lpp3 contains
      a variant sequence, Arg-Gly-Glu (RGE). Whether the RGE motif of murine Lpp3
      mediates cell-cell interaction has not been studied. In this report, we test the
      hypothesis that the cell adhesion function of the LPP3 protein is conserved
      across mouse and human. A glutathione S-transferase (GST) fusion protein of the
      proposed second extracellular loop of the murine Lpp3 sequence (GST-mLpp3-RGE)
      promoted attachment of cells in a long-term cell adhesion assay. GST-mLpp3-RGE
      interacted with alpha(5)beta(1) and alpha(v)beta(3) integrins in a solid-phase
      ELISA, while a mutant control, GST-hLPP3-RAD, did not. Long-term adhesion of
      endothelial cells to GST-mLpp3-RGE induced phosphorylation of FAK, SHC, and CAS,
      whereas adhesion to GST-hLPP3-RAD failed to do so. Upon long-term adhesion both
      the GST-hLPP3-RGD and GST-mLpp3-RGE substrates bound to the alpha(5)beta(1)
      integrin of FRT-alpha(5)(+) cells, an interaction that was inhibited by an anti
      alpha(5) integrin antibody. In addition, a cell aggregation assay showed that the
      intact mLpp3-RGE protein interacts with alpha(5)beta(1) and alpha(v)beta(3)
      integrins expressed by adjacent cells, an interaction that can be blocked by
      GRGDSP peptides and anti-LPP3-RGD antibodies. These data, together with the known
      importance of integrins in angiogenesis, provide a mechanism for the function of
      LPP3 in cell-cell interactions in both human and mouse.

PMID- 16099423
TI  - Geldanamycin-induced degradation of Chk1 is mediated by proteasome.
AB  - Checkpoint kinase 1 (Chk1) is a cell cycle regulator and a heat shock protein 90
      (Hsp90) client. It is essential for cell proliferation and survival. In this
      report, we analyzed the mechanisms of Chk1 regulation in U87MG glioblastoma cells
      using Geldanamycin (GA), which interferes with the function of Hsp90. GA reduced
      Chk1 protein level but not its mRNA level in glioblastoma cells. Co-treatment
      with GA and cycloheximide (CHX), a protein synthesis inhibitor, induced a
      decrease of half-life of the Chk1 protein to 3h and resulted in Chk1 down
      regulation. CHX alone induced only 32% reduction of Chk1 protein even after 24h.
      These findings indicated that reduction of Chk1 by GA was due to destabilization
      and degradation of the protein. In addition, GA-induced down-regulation of Chk1
      was reversed by MG132, a specific proteasome inhibitor. And it was revealed that
      Chk1 was ubiquitinated by GA. These results have indicated that degradation of
      Chk1 by GA was mediated by the ubiquitin-proteasome pathway in U87MG glioblastoma
      cells.

PMID- 16099424
TI  - At least two regions of the oncoprotein Tre2 are involved in its lack of GAP
      activity.
AB  - The product of the human Tre2 oncogene is structurally related to the Ypt/Rab
      GTPase-activating proteins (Ypt/Rab GAPs). Particularly, the oncoprotein shares
      with the yeast proteins Msb3p and Msb4p, and with the human protein RN-tre the
      highly conserved TBC domain, forming the catalytically active domain of Ypt/Rab
      GAPs. Yet, the Tre2 oncogene seems to encode a nonfunctional Rab GAP. As regions
      flanking the TBC domain may be crucial for catalytic activity, regions located N-
      and C-terminally with respect to this domain were explored. For this, chimeric
      proteins created by sequence exchanges between the Tre2 oncoprotein and RN-tre
      were tested for their ability to replace functionally the Msb3p and Msb4p
      proteins in double-mutant yeast cells. These complementation experiments
      revealed, in addition to the TBC domain, a second Tre2 region involved in the
      oncoprotein's lack of GAP activity: a 93-aa region flanking the TBC domain on the
      C-terminal side.

PMID- 16099425
TI  - Regulation of Bcl-3 through interaction with the Lck tyrosine kinase.
AB  - bcl-3 is a protooncogene which undergoes chromosomal translocation in a subset of
      chronic B-cell lymphocytic leukemia cells. Bcl-3 is a unique IkappaB family
      protein that regulates transcription of a number of NF-kappaB target genes
      through interactions with NF-kappaB dimers. Based on previous studies, suggesting
      that Bcl-3 interacts with the Fyn tyrosine kinase in platelets, we investigated
      possible interactions of Bcl-3 with Lck, a related tyrosine kinase important in
      lymphoid cells. Protein-protein interactions between Bcl-3 and the Lck tyrosine
      kinase were identified both in vitro and in vivo. Lck enhanced Bcl-3-mediated
      activation of a p52/Bcl-3-responsive promoter in reporter gene assays independent
      of its tyrosine kinase activity, but requiring the Lck SH3 protein interaction
      domain. These studies suggest that Bcl-3 might participate in oncogenic pathways
      involving Lck.

PMID- 16099426
TI  - Functional cytoplasmic domains of the Mac-1 integrin receptor in phorbol ester
      treated U937 cells.
AB  - The integrin receptor Mac-1 regulates adherence and survival of activated tissue
      macrophages but the underlying molecular mechanisms are poorly understood.
      Phorbol ester-induced macrophagic differentiation in U937 cells leads to surface
      expression of Mac-1 and its activation as well. We have attempted to determine
      essential amino acids for these activities in the cytoplasmic regions of CD11b
      and CD18 subunits by deletion mutagenesis. There was complete correlation between
      adherence and survival. Those deletions that lead to loss of adherence and
      enhanced apoptosis are truncation of CD11b before the MSEGG sequence; CD18
      internal deletion of either the membrane-proximal residues before the NPLF
      sequence or the NPLF sequence itself; CD18 truncation of the C-terminal residues
      after the NPLF sequence. Unexpectedly, when the NPLF sequence and the C-terminal
      residues were removed together by truncation, the adherent, antiapoptotic
      properties were restored. These results were discussed in terms of protein
      interaction with Mac-1 cytoplasmic regions.

PMID- 16099427
TI  - Anthrax edema factor potency depends on mode of cell entry.
AB  - Anthrax edema factor (EF) is a highly active calmodulin-dependent adenylyl
      cyclase toxin that can potently raise intracellular cAMP levels causing a broad
      range of tissue damage. EF needs anthrax protective antigen (PA) to enter into
      the host cell and together they form edema toxin. Here, we examine factors that
      are critical for edema toxin cell entry and potency. In Y1, 293T and mouse
      embryonic fibroblast cells, EF causes cell rounding, aggregation, and sometimes
      detachment via protein kinase A but not Epac. The rate-limiting step for these EF
      mediated effects is cellular entry via the anthrax toxin receptor. Finally, EF
      potency is also enhanced if the EF adenylyl cyclase domain is transfected into
      host cells, even in the absence of the anthrax PA-binding domain. These results
      indicate that the effects of EF in cells can differ dependent upon the mode of
      cellular entry of the adenylyl cyclase.

PMID- 16099428
TI  - Roles of mTOR and JNK in serine phosphorylation, translocation, and degradation
      of IRS-1.
AB  - In 3T3-L1 adipocytes, insulin or anisomycin stimulated phosphorylation of IRS-1
      at Ser(307) and Ser(636/639), both of which were partially reduced by the mTOR
      inhibitor, rapamycin, or the JNK inhibitor, SP600125, and were further inhibited
      by a combination of them. Interestingly, anisomycin-induced p70(S6K)
      phosphorylation was reduced by SP600125, while insulin-induced p70(S6K)
      phosphorylation was not. Furthermore, unlike insulin, anisomycin failed to elicit
      translocation or degradation of IRS-1. These results indicate that mTOR and JNK
      play roles in phosphorylating IRS-1 serine residues, and that insulin and
      anisomycin are different in terms of the relationship of activation between mTOR
      and JNK, and the effects on IRS-1 localization and stability.

PMID- 16099429
TI  - Glimepiride activates eNOS with a mechanism Akt but not caveolin-1 dependent.
AB  - Insulin stimulates caveolin-1 and eNOS phosphorylation. The sulfonylurea
      glimepiride mimics several insulin actions by mechanisms that are poorly
      understood. Glimepiride induces caveolin-1 phosphorylation and activates PI3K and
      Akt in rat adipocytes. In this paper, we investigated the effect of glimepiride
      on eNOS activation in human endothelial cells. We found that glimepiride induces
      caveolin-1 and eNOS phosphorylation. To better understand the role of caveolin-1
      in glimepiride action, we downregulated caveolin-1 expression by specific siRNA
      transfection. Caveolin-1 silencing did not change eNOS and Akt phosphorylation
      induced by glimepiride. On the contrary, LY294002, a specific PI3K inhibitor,
      blocked eNOS serine 1177 phosphorylation. These findings suggest that glimepiride
      induces eNOS phosphorylation in endothelial cells through an Akt-dependent
      mechanism, not regulated by caveolin-1.

PMID- 16099430
TI  - Nucleophosmin/B23 regulates PCNA promoter through YY1.
AB  - Ectopic over-expression of nucleophosmin/B23 caused a marked up-regulation in the
      amounts of Yin Yang 1 (YY1) and proliferating cellular nuclear antigen (PCNA)
      proteins. Transfection with nucleophosmin/B23-targeting siRNA induced a decrease
      in the intracellular amounts of nucleophosmin/B23, YY1, and PCNA. PCNA expression
      and its promoter activity were attenuated either by nucleophosmin/B23-siRNA or
      YY1-siRNA. The ChIP assay showed that positive regulation of PCNA is achieved by
      binding of YY1 to the initiation site of PCNA promoter. The binding of YY1 to the
      PCNA promoter and histone H4 acetylation was significantly decreased in
      nucleophosmin/B23-siRNA-treated cells as compared to control vector-transfected
      cells. Mutation in YY1 binding site resulted in the loss of PCNA promoter
      activity and the binding of YY1 to the promoter. The results have indicated that
      YY1 binds to the initiation site of the PCNA promoter along with histone H4
      acetylation, leading to transcriptional activity. We have demonstrated that
      nucleophosmin/B23 plays an important role in the regulation of PCNA through YY1.

PMID- 16099431
TI  - Insulin-induced stimulation of JNK and the PI 3-kinase/mTOR pathway leads to
      phosphorylation of serine 318 of IRS-1 in C2C12 myotubes.
AB  - Increased serine/threonine phosphorylation of insulin receptor substrate-1 (IRS
      1) is associated with cellular insulin resistance. We have recently identified
      serine 318 (Ser318) as a novel protein kinase C-zeta (PKC-zeta)-dependent
      phosphorylation site within IRS-1. As other kinases may phosphorylate at this
      serine residue as well, we aimed to identify such kinases in the present study.
      In C2C12 myotubes, exposure to insulin or phorbol ester markedly increased Ser318
      phosphorylation. In contrast, high glucose, tumor necrosis factor-alpha, and free
      fatty acids did not provoke Ser318 phosphorylation. JNK and the PI 3-kinase/mTOR
      pathway were found to be implicated in insulin-induced Ser318 phosphorylation,
      but not in TPA-stimulated phosphorylation that was, at least partly, mediated by
      classical or novel PKC. In conclusion, with JNK and the PI 3-kinase/mTOR pathway
      as mediators of insulin-induced Ser318 phosphorylation, we have identified
      kinases that have previously been reported to play key roles in phosphorylation
      of other serine residues in IRS-1.

PMID- 16099432
TI  - Nitrophorin synthesis is modulated by protein kinase CK2.
AB  - Rhodnius prolixus is a blood-sucking bug whose saliva contains a family of nitric
      oxide-carrying proteins named nitrophorins (NPs). Saliva is injected into the
      host bloodstream during insect feeding. Nitric oxide is then released from NPs
      and will act on vascular smooth muscle, promoting vasodilation. Epithelial cells
      of salivary glands then undergo a massive synthesis of antihemostatics including
      NPs which produces saliva for the next blood meal. Here, we demonstrate the
      transient activation of a protein kinase in the salivary glands of R. prolixus
      after a blood meal. Biochemical, immunological, and pharmacological assays were
      used to identify this enzyme as protein kinase CK2. CK2 is activated after a
      blood meal and decreases to basal levels when salivary gland refilling is
      resumed. Inhibition of CK2 blocked [(35)S]methionine incorporation into newly
      synthesized salivary gland proteins in cultured tissue. Dissected salivary glands
      were then incubated with the heme fluorescent analog palladium (II) mesoporphyrin
      IX (Pd-MP) in the presence of a selective cell-permeable CK2 inhibitor, TBB
      (4,5,6,7-tetrabromobenzotriazole). NP synthesis was quantified based on
      fluorescence of the Pd-MP group bound to the NP heme pocket. TBB dramatically
      blocked NP synthesis. Altogether, these data are the first demonstration to show
      that antihemostatic synthesis in a blood-sucking arthropods is under protein
      phosphorylation control.

PMID- 16099433
TI  - Chromatin-related proteins in pluripotent mouse embryonic stem cells are
      downregulated after removal of leukemia inhibitory factor.
AB  - Embryonic stem (ES) cells have generated enormous interest due to their capacity
      to self-renew and the potential for growing many different cell types in vitro.
      Leukemia inhibitory factor (LIF), bone morphogenetic proteins, octamer-binding
      protein 3 or 4, and Nanog are important factors in the maintenance of
      pluripotency in mouse ES cells. However, the mechanisms by which these factors
      regulate the pluripotency remain poorly understood. To identify other proteins
      involved in this process, we did a proteomic analysis of mouse ES cells that were
      cultured in the presence or absence of LIF. More than 100 proteins were found to
      be involved specifically in either the differentiation process or the maintenance
      of undifferentiated state. Among these, chromatin-related proteins were
      identified as the major proteins in nuclear extracts of undifferentiated cells.
      Analysis with real-time RT-PCR revealed that enrichment of these proteins in
      pluripotent ES cells was regulated at the transcriptional levels. These results
      suggest that specific chromatin-related proteins may be involved in maintaining
      the unique properties of pluripotent ES cells.

PMID- 16099434
TI  - Cloning, high level expression of human paraoxonase-3 in Sf9 cells and
      pharmacological characterization of its product.
AB  - Human paraoxnase-3 (hPON3) (EC3.1.8.1) is a lipid-associated enzyme with
      antioxidant activity, and can inhibit the oxidation of low-density lipoprotein
      (LDL), thereby inhibiting early atherogenic process. In the present study, human
      PON3 gene was cloned from Human Fetal Liver Marathon-Ready cDNA and expressed in
      insect cells using baculovirus vector. Twenty-eight milligrams of purified
      recombinant hPON3 (rhPON3) was obtained from 1L Sf9 cells culture. The Km and
      Vmax values of rhPON3, with respective to phenylacetate hydrolysis were 7.46+/
      4.40 mM and 89+/-10.54 U/mg (n=3). The kinetic parameters of Vmax and Km for
      dihydrocoumarin hydrolysis by rhPON3 were 698+/-248 U/mg and 0.84+/-0.24 mM
      (n=3). LDL oxidation assay indicated that rhPON3 could effectively protect LDL
      against copper-induced oxidation in vitro.

PMID- 16099436
TI  - Information transmission rate changes of retinal ganglion cells during contrast
      adaptation.
AB  - During adaptation to high-contrast stimulation, retinal ganglion cell's
      responsiveness change is characterized by decreased firing rate and declined
      sensitivity. In order to examine the modification of information transmission
      properties of the ganglion cell during this adaptation process, neural activities
      were recorded extracellularly from the chicken retina using a multi-electrode
      recording system, and the information transmission rate of the retinal ganglion
      cells was estimated. The results show that the response entropy and noise entropy
      of the ganglion cells both decreased during the adaptation process, which
      resulted in a modest decline of information transmission rate of ganglion cells
      after several seconds' adaptation. However, due to the decrease of the neuron's
      firing rate during the adaptation, it is revealed that the information carried by
      each spike was increased as compared to pre-adaptation, suggesting that retinal
      ganglion cells' information processing strategies during contrast adaptation may
      reflect economical principle by promoting each spike more informative. These
      results also suggest that contrast adaptation and sensitivity rescaling of the
      visual neurons provide an efficient manner in information transmission and save
      the system's metabolic cost in the meantime.

PMID- 16099435
TI  - Up-regulation of Mrp4 expression in kidney of Mrp2-deficient TR- rats.
AB  - Multidrug resistance-associated proteins (Mrps) are a group of ATP-dependent
      efflux transporters for organic anions. Mrp2 and Mrp4 are co-localized to the
      apical (brush-border) membrane domain of renal proximal tubules, where they may
      function together in the urinary excretion of organic anions. Previous reports
      showed that urinary excretion of some organic anions is not impaired in transport
      deficient (TR-) rats, which lack Mrp2, suggesting that up-regulation of other
      transporter(s) may compensate for the loss of Mrp2 function. The purpose of this
      study was to determine whether Mrp4 expression in kidney is altered in TR- rats.
      Mrp4 mRNA expression was quantified using the high-throughput branched DNA signal
      amplification assay. Mrp4 protein expression was determined by Western blot and
      immunohistochemical analysis. Mrp4 mRNA in kidney of TR- rats was 100% higher
      than normal Wistar rats. Western blot analysis showed a 200% increase in Mrp4
      protein expression in kidney of the mutant rats compared to normal rats.
      Immunohistochemical analysis of Mrp4 protein demonstrated apical localization of
      Mrp4 on renal proximal tubules, and that the immunoreactivity was more intense in
      kidney sections from TR- rats than those from normal rats. In summary, the
      results of the present study demonstrate that renal Mrp4 expression is up
      regulated in TR- rats, which may explain why urinary excretion of some organic
      anions remains normal in the mutant rats.

PMID- 16099437
TI  - A new approach to inhibiting astrocytic IP3-induced intracellular calcium
      increase in an astrocyte-neuron co-culture system.
AB  - Astrocytes exhibit dynamic Ca2+ mobilization, such as Ca2+ wave and Ca2+
      oscillation, via an inositol 1,4,5-triphosphate-induced Ca2+ release (IICR)
      dependent mechanism. The physiological functions of astrocytic Ca2+ mobilization,
      however, are poorly understood. To investigate this issue, we created a plasmid
      encoding an enhanced green fluorescent protein-tagged inositol 1,4,5-triphosphate
      absorbent protein and expressed it in cultured astrocytes. Expression of this
      protein inhibited both IICR and the Ca2+ wave in cultured astrocytes. By
      combining this method to the single cell electroporation technique, we were able
      to inhibit IICR specifically in astrocytes in an astrocyte-neuron co-culture
      system. Our approach provides a useful tool for direct examination of the
      physiological role of astrocytic Ca2+ signaling on neuronal function.

PMID- 16099438
TI  - NOC/oFQ activates ERK and JNK but not p38 MAPK to impair prostaglandin
      cerebrovasodilation after brain injury.
AB  - Fluid percussion brain injury (FPI) elevates the CSF concentration of the opioid
      nociceptin/orphanin FQ (NOC/oFQ), which contributes to impairment of pial artery
      dilation to the prostaglandins (PG) PGE2 and PGI2. This study investigated the
      role of the ERK, p38, and JNK isoforms of mitogen-activated protein kinase (MAPK)
      in impaired PG cerebrovasodilation after FPI, and the relationship of brain
      injury induced release of NOC/oFQ to MAPK in such vascular impairment in newborn
      pigs equipped with a closed cranial window. FPI blunted PGE2 pial artery
      dilation, but U 0126 and SP 600125 (10(-6) M) (ERK and JNK MAPK inhibitors,
      respectively) partially prevented such impairment (7 +/- 1, 12 +/- 1, and 17 +/-
      1 vs. 2 +/- 1, 3 +/- 1, and 5 +/- 1 vs. 4 +/- 1, 7 +/- 1, and 12 +/- 1% for 1,
      10, and 100 ng/ml PGE2 in control, FPI, and FPI + U 0126 pretreated animals,
      respectively). In contrast, administration of SB 203580 (10(-5) M) (p38 MAPK
      inhibitor) did not prevent FPI impairment of PGE2 dilation. Co-administration of
      NOC/oFQ at the dose of 10(-10) M, the cerebrospinal fluid concentration observed
      after FPI, with PGE2 under non-brain injury conditions blunted PG dilation, but U
      0126 or SP 600125 partially prevented such impairment (7 +/- 1, 11 +/- 1, and 16
      +/- 2 vs. 0 +/- 1, 1 +/- 1, and 2 +/- 1, vs. 5 +/- 1, 9 +/- 1, and 13 +/- 2 for
      responses to PGE2 in control, NOC/oFQ, and NOC/oFQ + U 0126 treated animals,
      respectively). Administration of SB 203580 did not prevent impairment of PG pial
      artery dilation by NOC/oFQ. These data show that activation of ERK and JNK but
      not p38 MAPK contributes to impairment of PG cerebrovasodilation after FPI. These
      data suggest that NOC/oFQ induced ERK and JNK but not p38 MAPK activation
      contributes to impaired cerebrovasodilation to PG after FPI.

PMID- 16099439
TI  - Reconstruction of intraoral defects using facial artery musculomucosal flap.
AB  - The facial artery musculomucosal flap, technically a combination of the
      nasolabial flap and the buccal mucosal flap, has been a reliable, versatile flap,
      either superiorly or inferiorly based for reconstruction of a wide variety of
      postcancer excision intraoral mucosal defects including defects of the palate,
      alveolus, lips and floor of mouth. We have used it 17 times in 16 patients with
      no failures and one flap with terminal necrosis. Almost all flaps developed
      venous congestion which settled on its own by conservative management.

PMID- 16099440
TI  - New 6-butylamino-6-deoxycellulose and 6-deoxy-6-pyridiniumcellulose derivatives
      with highest regioselectivity and completeness of reaction.
AB  - This paper investigates the nucleophilic substitution (S(N)) reactions of
      tosylcellulose with butylamine and pyridine, respectively. The S(N) reactions of
      tosylcellulose 1 (DS(Total) 2.02; DS(C-6) 1.0) with butylamine carried out at 25,
      50, 75 and 100 degrees C in both dimethyl sulfoxide (DMSO) and pure butylamine
      showed that the regioselectivity of substitution at C-6 of cellulose is
      temperature dependent: the highest regioselectivity at C-6 can be reached at 25
      and 50 degrees C; substitution at C-2 also occurred at 75 and 100 degrees C. The
      substitution speed in pure butylamine is greater than that in the presence of
      DMSO. A complete and regioselective substitution at C-6 with a DS of 1.0 was
      obtained under the conditions of 50 degrees C, 40 h in butylamine. The
      substitution reactions of 1 with pyridine carried out at 25, 50, 75 and 100
      degrees C for 24h in DMSO did not occur. In contrast to this the S(N) reactions
      done in pure pyridine showed that a temperature- and steric-dependent,
      regioselective substitution took place at C-6 at temperatures from 25 to 145
      degrees C. The highest regioselectivity and completeness at C-6 can be obtained
      at 100 degrees C for 90 h, whereas at 145 degrees C substitution also occurs at C
      2. The results were proved by 1H NMR and 13C NMR spectroscopy.

PMID- 16099441
TI  - Interleukin-1 receptor antagonist alters the response to vessel wall injury in a
      porcine coronary artery model.
AB  - OBJECTIVE: To determine the influence of IL-1 on the arterial response to
      experimental injury in porcine models of percutaneous coronary intervention
      (PCI). METHODS: An intravenous (i.v.) bolus of 0.5 mg/kg followed by a
      subcutaneous (s.c.) infusion of 2 mg/kg/24 h of human IL-1 receptor antagonist
      (IL-1ra) inhibited neutrophil recruitment in response to intradermal IL-1. Using
      this dose regimen, five groups of pigs were studied: Group 1, oversized balloon
      angioplasty of 2 coronary vessels (14-day infusion, 28th day sacrifice and
      analysis); Groups 2, 3, 4, and 5, oversized stenting of 2 coronary vessels (Group
      2: 14-day infusion, 28th day analysis; Group 3: 14-day infusion, 14th day
      analysis; Group 4: 28-day infusion, 28th day analysis; Group 5: 28-day infusion,
      90th day analysis). Neointimal area was quantified by standard means. RESULTS: In
      Group 1, IL-1ra resulted in a 23% decrease in neointimal area (p=0.04); in Group
      2, a 34% increase (p=0.001); in Group 3, a 38% decrease (p<0.0001); in Group 4, a
      34% decrease (p=0.0004); and in Group 5, a 41% decrease (p=0.00001). CONCLUSIONS:
      IL-1ra was associated with a sustained, significant reduction in neointima after
      vessel wall injury as long as it is given for the duration of the stimulation of
      the IL-1 system, in this case at least 28 days. This suggests that therapies
      based on the antagonism of IL-1 may modulate the coronary artery response to
      injury.

PMID- 16099442
TI  - Phenotypic adaptation of the late preconditioned heart: myocardial oxygen
      consumption is reduced.
AB  - OBJECTIVES: Although the signalling pathways of late preconditioning have been
      extensively investigated, its consequence for myocardial metabolism remains
      unknown. Thus, myocardial oxygen consumption (MVO2) was evaluated before and
      under late preconditioning. METHODS: In 7 chronically instrumented dogs, we
      measured MVO2 in vivo at baseline and during inotropic stimulation with
      dobutamine (10 and 20 microg/kg/min, i.v.) before (Day 0) and 24 h after (Day 1)
      a 10-min circumflex coronary artery occlusion. RESULTS: At Day 0, dobutamine dose
      dependently increased the triple product (heart ratexleft ventricular systolic
      pressurexleft ventricular maximum dP/dt), MVO2, coronary blood flow, and coronary
      sinus pO2. At Day 1, the triple product was similar at baseline and at each dose
      of dobutamine but MVO2 was significantly blunted as compared to Day 0 (-15+/-4%, 
      22+/-3% and -19+/-4% at baseline, dobutamine 10 and 20 microg/kg/min,
      respectively). Importantly, the relationship between MVO2 and triple product was
      significantly rightward shifted with late preconditioning, i.e., MVO2 was reduced
      for any level of triple product. At Day 1, the relationship between coronary
      blood flow and MVO2 was not altered as compared to Day 0 but coronary sinus pO2
      was significantly increased vs. Day 0 for any level of coronary blood flow,
      suggesting that late preconditioning exerted no vasomotor effect but rather
      changed myocardial oxygen handling. These effects were abolished by
      administration of S-methyl-isothiourea (1.5 mg/kg, i.v.), a iNOS inhibitor.
      CONCLUSION: This study demonstrates that ischemic late preconditioning is
      characterized by a major reduction in MVO2, both at baseline and under inotropic
      stimulation. NO from iNOS contributes to this modification of metabolic
      phenotype.

PMID- 16099443
TI  - C-reactive protein: a potential new molecular link between inflammation,
      thrombosis and vascular cell proliferation?

PMID- 16099444
TI  - Oxidized LDL downregulates ATP-binding cassette transporter-1 in human vascular
      endothelial cells via inhibiting liver X receptor (LXR).
AB  - OBJECTIVE: ATP-binding cassette transporter-1 (ABCA1) mediates the active efflux
      of cholesterol and phospholipids, playing an important role in cholesterol
      homeostasis and atherogenesis. Oxidized low density lipoprotein (oxLDL) is an
      atherogenic molecule associated with the vascular endothelial dysfunction and
      development of atherosclerotic plaque. This report describes the effect of copper
      catalyzed oxLDL on the regulation of ABCA1 in human endothelial cells (ECs).
      METHODS AND RESULTS: oxLDL downregulated ABCA1 at both mRNA and protein levels in
      a dose-dependent manner. This inhibitory effect of oxLDL was observed with both
      minimally and extensively oxLDL. Transfection of the ABCA1 promoter luciferase
      revealed oxLDL to substantially decrease ABCA1 promoter activity at basal
      conditions and after stimulation by overexpressing the liver X receptor LXRalpha
      and retinoid X receptor RXRalpha. oxLDL also attenuated LXR activation by
      blocking LXR ligand binding and interfering with the generation of 27
      hydroxycholesterol, an LXR endogenous ligand. Furthermore, oxLDL inhibited
      exogenous cholesterol- and oxysterol-induced endothelial ABCA1 induction.
      CONCLUSION: oxLDL downregulated ABCA1 by inhibiting LXR activation in endothelial
      cells. Such an effect may contribute to endothelial dysfunction and plaque
      formation.

PMID- 16099445
TI  - How much intimacy is compatible with survival for a cardiomyocyte?

PMID- 16099446
TI  - Stretch-dependent modulation of [Na+]i, [Ca2+]i, and pHi in rabbit myocardium--a
      mechanism for the slow force response.
AB  - OBJECTIVE: Rabbit ventricular myocardium is characterized by a biphasic response
      to stretch with an initial, rapid increase in force followed by a delayed, slow
      increase in force (slow force response, SFR). The initial phase is attributed to
      increased myofilament Ca(2+) sensitivity, but the mechanisms of the delayed phase
      are only incompletely understood. We tested whether stretch-dependent stimulation
      of Na(+)/H(+) exchange (NHE1) and consecutive changes in pH(i) and/or [Na(+)](i)
      may underlie the SFR. METHODS: Isometric contractions of rabbit ventricular
      muscles were recorded in bicarbonate-containing Tyrode's (Tyrode) or bicarbonate
      free HEPES-buffered solution (HEPES). Muscles were loaded with the Ca(2+)
      indicator aequorin, the pH indicator BCECF, or the Na(+) indicator SBFI and
      rapidly stretched from 88% (L(88)) to 98% (L(98)) of optimal length. The
      resulting immediate and slow increases in twitch force (1st phase and SFR) as
      well as changes in [Ca(2+)](i), [Na(+)](i), or pH(i) were quantified before and
      after inhibition of NHE1 by HOE 642 (3 microM) or reverse-mode Na(+)/Ca(2+)
      exchange (NCX) by KB-R 7943 (5 microM). RESULTS: In both Tyrode (n=21) and HEPES
      (n=22), developed force increased to approximately 160% during the 1st phase
      followed by a further increase to approximately 205% during the SFR. The SFR was
      accompanied by a 21% increase of the aequorin light transient (n=4; normalized to
      the 1st phase) and a approximately 3 mM increase in [Na(+)](i) (n=4-7). The SFR
      was also associated with an increase in pH(i). However, this increase was delayed
      and was significant only after the SFR had reached its maximum. The delayed pH(i)
      increase was larger in HEPES than in Tyrode. HOE 642 and/or KB-R 7943 reduced the
      SFR by approximately 30-40%. In addition, HOE 642 diminished the stretch-mediated
      elevation of [Na(+)](i) by 72% and the delayed alkalinization. CONCLUSIONS: The
      data are consistent with the hypothesis that SFR results from increases in
      [Ca(2+)](i) secondary to altered flux via NCX in part resulting from increases in
      [Na(+)](i) mediated by NHE1.

PMID- 16099447
TI  - The role of nutrition in creation of the eye imaginal disc and initiation of
      metamorphosis in Manduca sexta.
AB  - With the exception of the wing imaginal discs, the imaginal discs of Manduca
      sexta are not formed until early in the final larval instar. An early step in the
      development of these late-forming imaginal discs from the imaginal primordia
      appears to be an irreversible commitment to form pupal cuticle at the next molt.
      Similar to pupal commitment in other tissues at later stages, activation of broad
      expression is correlated with pupal commitment in the adult eye primordia.
      Feeding is required during the final larval instar for activation of broad
      expression in the eye primordia, and dietary sugar is the specific nutritional
      cue required. Dietary protein is also necessary during this time to initiate the
      proliferative program and growth of the eye imaginal disc. Although the hemolymph
      titer of juvenile hormone normally decreases to low levels early in the final
      larval instar, eye disc development begins even if the juvenile hormone titer is
      artificially maintained at high levels. Instead, creation of the late-forming
      imaginal discs in Manduca appears to be controlled by unidentified endocrine
      factors whose activation is regulated by the nutritional state of the animal.

PMID- 16099448
TI  - Activation of a pertussis toxin-sensitive, inhibitory G-protein is necessary for
      steroid-mediated oocyte maturation in spotted seatrout.
AB  - Oocyte maturation (OM) is initiated in lower vertebrates and echinoderms when
      maturation-inducing substances (MIS) bind oocyte membrane receptors. This study
      tested the hypothesis that activation of a G(i) protein is necessary for MIS
      mediated OM in spotted seatrout. Addition of MIS significantly decreased adenylyl
      cyclase activity in a steroid specific, pertussis toxin (PTX)-sensitive manner in
      oocyte membranes and microinjection of PTX into oocytes inhibited MIS-induced OM,
      suggesting the steroid activates a G(i) protein. MIS significantly increased
      [(35)S]GTPgammaS binding to ovarian membranes, confirming that MIS receptor
      binding activates a G-protein, and immunoprecipitation studies showed the
      increased [(35)S]GTPgammaS binding was associated with Galpha(i1-3) proteins.
      Radioligand binding studies in ovarian membranes using GTPgammaS and PTX
      demonstrated that the MIS binds a receptor coupled to a PTX-sensitive G-protein.
      This study provides the first direct evidence in a vertebrate model that MIS
      induced activation of a G(i) protein is necessary for OM. These results support a
      mechanism of MIS action involving binding to a novel, G-protein coupled receptor
      and activation of an inhibitory G-protein, the most comprehensive and plausible
      model of MIS initiation of OM proposed to date.

PMID- 16099449
TI  - Cholesterol content regulates acrosomal exocytosis by enhancing Rab3A plasma
      membrane association.
AB  - The acrosome is an exocytic granule that overlies the spermatozoan nucleus. In
      response to different stimuli, it undergoes calcium-regulated exocytosis. Freshly
      ejaculated mammalian sperm are not immediately capable of undergoing acrosome
      reaction. The acquisition of this ability is called capacitation and involves a
      series of still not well-characterized changes in the sperm physiology. Plasma
      membrane cholesterol removal is one of the sperm modifications that are
      associated with capacitation. However, how sterols affect acrosomal exocytosis is
      unknown. Here, we show that short incubations with cyclodextrin, a cholesterol
      removal agent, just before stimulation promote acrosomal exocytosis. Moreover,
      the effect was also observed in permeabilized cells stimulated with calcium,
      indicating that cholesterol plays a direct role in the calcium-dependent
      exocytosis associated with acrosome reaction. Using a photo-inhibitable calcium
      chelator, we show that cholesterol affects an early event of the exocytic cascade
      rather than the lipid bilayers mixing. Functional data indicate that one target
      for the cholesterol effect is Rab3A. The sterol content does not affect the Rab3A
      activation-deactivation cycle but regulates its membrane anchoring. Western blot
      analysis and immunoelectron microscopy confirmed that cholesterol efflux
      facilitates Rab3A association to sperm plasma membrane. Our data indicate that
      the cholesterol efflux occurring during capacitation optimizes the conditions for
      the productive assembly of the fusion machinery required for acrosome reaction.

PMID- 16099450
TI  - Lead dust in Broken Hill homes: effect of remediation on indoor lead levels.
AB  - This study was undertaken to determine whether home remediation effectively
      reduced indoor lead levels in Broken Hill, a long-established silver-lead-zinc
      mining town in outback Australia. A before-after study of the effect of home
      remediation on indoor lead levels was embedded into a randomized controlled trial
      of the effectiveness of remediation for reducing elevated blood lead levels in
      young children. Moist towelettes were used to measure lead loading (microg/m2) on
      internal windowsills and internal and entry floors of 98 homes; samples were
      collected before, immediately after, and 2, 4, 6, 8, and 10 months after
      remediation. Data were log(10) transformed for the analysis. Remediation reduced
      average indoor lead levels by approximately 50%, and lead levels remained low for
      the duration of the follow-up period (10 months). The greatest gains were made in
      homes with the highest initial lead levels; homes with low preremediation lead
      levels showed little or no benefit. Before remediation, homes located in areas
      with high soil lead levels or with "poor" dust proofing had higher lead levels
      than those in areas with lower soil lead levels or with "medium" or "good" dust
      proofing; these relative differences remained after remediation. There was no
      evidence that lead loading was reduced by an increased opportunity to become
      aware of lead issues. We conclude that remediation is an effective strategy for
      reducing the lead exposure of children living in homes with high indoor lead
      levels.

PMID- 16099452
TI  - Phencyclidine-induced cognitive deficits in mice are improved by subsequent
      subchronic administration of clozapine, but not haloperidol.
AB  - This study was undertaken to examine the effects of subsequent administration of
      antipsychotic drugs (clozapine and haloperidol) on cognitive deficits in mice
      after repeated administration of phencyclidine (PCP). In the novel object
      recognition test, repeated administration of PCP (10 mg/kg) significantly
      decreased exploratory preference in the retention test session but not in the
      training test session. PCP-induced deficits were significantly improved by
      subsequent subchronic (2 weeks) administration of clozapine (5 mg/kg), but not
      haloperidol (0.1 mg/kg). These findings suggest that PCP-induced cognitive
      deficits using the novel object recognition test may be a potential animal model
      of atypical antipsychotic activity.

PMID- 16099453
TI  - In vitro properties of 5-(benzylsulfonyl)-4-bromo-2-methyl-3(2H)-pyridazinone: a
      novel permeability transition pore inhibitor.
AB  - Despite the increasing implication of the permeability transition pore (PTP) in
      the pathophysiology of neurodegenerative diseases, few selective PTP inhibitors
      have been reported so far. Here, we evaluate the pharmacological properties of a
      novel PTP inhibitor, BBMP (5-(benzylsulfonyl)-4-bromo-2-methyl-3(2H)
      pyridazinone). This drug was discovered from the screening of a compound library
      against the PTP using a functional assay with isolated mitochondria. Similarly to
      cyclosporin A, the drug prevented Ca2+-induced permeability transition and
      mitochondrial depolarization. BBMP appeared more potent that minocycline in both
      swelling and membrane potential assays displaying pIC50 values of 5.5+/-0.1 and
      5.6+/-0.0, respectively. Unlike minocycline, BBMP dose-dependently prevented DNA
      fragmentation induced by KCl 25/5 mM shift and serum deprivation in cerebellar
      granule neurons with a pIC50 of 5.7+/-0.6. The inhibition of PTP-mediated
      cytochrome c release observed in isolated mitochondria at 10 and 100 microM may
      explain its neuroprotective properties in vitro. These data suggest that the
      mitochondrial PTP is potentially involved in neuronal cell death and that PTP
      inhibitors, like BBMP, may possess a therapeutic potential in neurodegenerative
      disorders.

PMID- 16099454
TI  - Requirement of c-Jun NH2-terminal kinase activation in interferon-alpha-induced
      apoptosis through upregulation of tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) in Daudi B lymphoma cells.
AB  - Interferon alpha (IFN-alpha) inhibits growth, at least in part, through induction
      of apoptosis. However, the molecular mechanisms underlying IFN-alpha-induced
      apoptosis are not completely understood. In the present study, we found that IFN
      alpha induced a sustained activation of c-Jun N-terminal kinase 1 (JNK1), but not
      extracellular kinases (ERKs), in Daudi B lymphoma cells, as assessed by Western
      blotting using phospho-specific antibodies. Several lines of evidence support the
      notion that the IFN-alpha-induced activation of JNK is responsible for IFN-alpha
      induced apoptosis, at least in part, through upregulation of TNF-related
      apoptosis-inducing ligand (TRAIL). First, pretreatment of Daudi cells with a JNK
      inhibitor reduced IFN-alpha-induced upregulation of TRAIL and loss of
      mitochondrial membrane potential (DeltaPsim) and annexin-positive cells, which
      was assessed by flow cytometry. Second, a dominant-negative form of JNK1 (dnJNK1)
      also reduced these apoptotic events, while a constitutively active form of JNK1,
      MKK7-JNK1beta, enhanced them. Finally, treatment with IFN-alpha enhanced the
      promoter activity of the TRAIL gene, which was partially abrogated by either JNK
      inhibitor or dnJNK1, while it was moderately enhanced by MKK7-JNK1beta. These
      findings are useful for understanding molecular mechanisms of IFN-alpha-induced
      apoptosis and also for development of treatment modalities of some tumors with
      IFN-alpha.

PMID- 16099456
TI  - Deletion of flavoredoxin gene in Desulfovibrio gigas reveals its participation in
      thiosulfate reduction.
AB  - The gene encoding Desulfovibrio gigas flavoredoxin was deleted to elucidate its
      physiological role in the sulfate metabolism. Disruption of flr gene strongly
      inhibited the reduction of thiosulfate and exhibited a reduced growth in the
      presence of sulfite with lactate as electron donor. The growth with sulfate was
      not however affected by the lack of this protein. Additionally, flr mutant cells
      revealed a decrease of about 50% in the H2 consumption rate using thiosulfate as
      electron acceptor. Altogether, our results show in vivo that during sulfite
      respiration, trithionate and thiosulfate are produced and that flavoredoxin is
      specific for thiosulfate reduction.

PMID- 16099455
TI  - Endogenous kynurenate controls the vulnerability of striatal neurons to
      quinolinate: Implications for Huntington's disease.
AB  - Excessive activation of NMDA receptors results in excitotoxic nerve cell loss,
      which is believed to play a critical role in the pathophysiology of Huntington's
      disease (HD) and several other catastrophic neurodegenerative diseases. Kynurenic
      acid (KYNA), a neuroinhibitory tryptophan metabolite, has neuroprotective
      properties and may serve as an endogenous anti-excitotoxic agent. This hypothesis
      was tested in the striatum, using mice with a targeted deletion of kynurenine
      aminotransferase II (KAT II), a major biosynthetic enzyme of KYNA in the
      mammalian brain. On post-natal day (PND) 14, the striatum of mkat-2-/- mice
      showed a reduction in KYNA levels but contained normal concentrations of the
      metabolically related neurotoxins 3-hydroxykynurenine and quinolinic acid (QUIN).
      Intrastriatal injections of QUIN, a NMDA receptor agonist, caused significantly
      larger lesions in these immature mutant mice than in age-matched wild-type
      animals. This lesion enlargement was not observed when mkat-2-/- mice were
      acutely pre-treated with the kynurenine 3-hydroxylase inhibitor UPF 648, which
      counteracted the striatal KYNA deficit. Moreover, no increased vulnerability to
      QUIN was observed in 2-month-old mkat-2-/- mice, which present with normal brain
      KYNA levels. Intrastriatal injections of the non-NMDA receptor agonist kainate
      caused similar lesion sizes in both genotypes regardless of age. These results
      indicate that endogenous KYNA preferentially controls the vulnerability of
      striatal neurons to QUIN. Our data suggest that timely pharmacological
      interventions resulting in an up-regulation of brain KYNA levels may benefit
      patients suffering from HD or other neurodegenerative diseases.

PMID- 16099457
TI  - Effects of N-acylethanolamines on the respiratory chain and production of
      reactive oxygen species in heart mitochondria.
AB  - Long-chain N-acylethanolamines (NAEs) have been found to uncouple oxidative
      phosphorylation and to inhibit uncoupled respiration of rat heart mitochondria
      [Wasilewski, M., Wieckowski, M.R., Dymkowska, D. and Wojtczak, L. (2004) Biochim.
      Biophys. Acta 1657, 151-163]. The aim of the present work was to investigate in
      more detail the mechanism of the inhibitory effects of NAEs on the respiratory
      chain. In connection with this, we also investigated a possible action of NAEs on
      the generation of reactive oxygen species (ROS) by respiring rat heart
      mitochondria. It was found that unsaturated NAEs, N-oleoylethanolamine (N-Ole)
      and, to a greater extent, N-arachidonoylethanolamine (N-Ara), inhibited
      predominantly complex I of the respiratory chain, with a much weaker effect on
      complexes II and III, and no effect on complex IV. Saturated N
      palmitoylethanolamine had a much smaller effect compared to unsaturated NAEs. N
      Ara and N-Ole were found to decrease ROS formation, apparently due to their
      uncoupling action. However, under specific conditions, N-Ara slightly but
      significantly stimulated ROS generation in uncoupled conditions, probably due to
      its inhibitory effect on complex I. These results may contribute to our better
      understanding of physiological roles of NAEs in protection against ischemia and
      in induction of programmed cell death.

PMID- 16099458
TI  - Wnt-3a regulates chondrocyte differentiation via c-Jun/AP-1 pathway.
AB  - Our previous study indicated that interleukin (IL)-1beta induces expression of
      several Wnt proteins in chondrocytes and causes chondrocyte dedifferentiation via
      the c-Jun/activator protein-1 (AP-1) pathway. This study examined whether Wnt-3a
      causes chondrocyte dedifferentiation via the c-Jun/AP-1 pathway. Wnt-3a inhibited
      chondrogenesis of mesenchymal cells by stabilizing cell-cell adhesion in a manner
      independent of beta-catenin transcriptional activity. Wnt-3a also induced
      dedifferentiation of articular chondrocytes by stimulating the transcriptional
      activity of beta-catenin-T cell-factor/lymphoid-enhancer-factor (Tcf/Lef)
      complex. In chondrocytes, Wnt-3a caused the expression of c-Jun and its
      phosphorylation by c-Jun N-terminal kinase (JNK), resulting in activation of AP
      1. AP-1 activation suppressed the expression of Sox-9, a major transcription
      factor regulating type II collagen expression. Collectively, our results suggest
      that Wnt-3a inhibits chondrogenesis by stabilizing cell-cell adhesion and that it
      causes dedifferentiation of chondrocytes by activating of beta-catenin-Tcf/Lef
      transcriptional complex and the c-Jun/AP-1 pathway.

PMID- 16099459
TI  - Exclusive paternal expression and novel alternatively spliced variants of epsilon
      sarcoglycan mRNA in mouse brain.
AB  - Mutations of SGCE encoding epsilon-sarcoglycan cause myoclonus-dystonia. SGCE is
      paternally expressed; however, 5-10% of patients show maternal inheritance of the
      disease. We found Sgce was exclusively paternally expressed in mice by using a
      novel polymorphism marker. The result was confirmed in Sgce heterozygous knockout
      mice. This finding suggests that maternally inherited myoclonus-dystonia may not
      result from maternal expression of SGCE. Furthermore, we report a new family of
      alternatively spliced Sgce mRNA expressed in the brain coding for different C
      terminal sequences possessing a PDZ-binding motif. Our results provide a better
      basis for diagnosis and understanding of the pathogenesis of myoclonus-dystonia.

PMID- 16099460
TI  - Rapid disruption of intestinal barrier function by gliadin involves altered
      expression of apical junctional proteins.
AB  - Coeliac disease is a chronic enteropathy caused by the ingestion of wheat gliadin
      and other cereal prolamines derived from rye and barley. In the present work, we
      investigated the mechanisms underlying altered barrier function properties
      exerted by gliadin-derived peptides in human Caco-2 intestinal epithelial cells.
      We demonstrate that gliadin alters barrier function almost immediately by
      decreasing transepithelial resistance and increasing permeability to small
      molecules (4 kDa). Gliadin caused a reorganisation of actin filaments and altered
      expression of the tight junction proteins occludin, claudin-3 and claudin-4, the
      TJ-associated protein ZO-1 and the adherens junction protein E-cadherin.

PMID- 16099461
TI  - CRH receptor type 1 mediates continual hypoxia-induced changes of immunoreactive
      prolactin and prolactin mRNA expression in rat pituitary.
AB  - We have reported that, in rats, hypoxia (10.8% O2) stimulates prolactin (PRL)
      release from the pituitary. This study is designed to compare the response of
      pituitary PRL to acute hypoxia (AH), continual hypoxia (CH), intermittent hypoxia
      (IH), cold, and restraint, individually and combined with hypoxia. This study
      also investigates the involvement of the corticotropin-releasing hormone receptor
      1 (CRH R1) in the hypoxia-induced PRL response. Hypoxia was induced by exposing
      the rats to high altitudes of 2 km (16.0% O2) or 5 km (10.8% O2). The PRL levels
      in the pituitary (iPRL) and in plasma (pPRL) were measured by immunocytochemistry
      and RIA assay, respectively. The acute hypoxia of 5 km for 2-24 h caused a
      biphasic change (early decrease and late increase) of PRL. Both CH and IH at 2 or
      5 km for 1-5 days markedly increased pPRL but decreased iPRL. Continual severe
      hypoxia (10.8% O2) for periods of 10, 15, and 25 days significantly enhanced pPRL
      but this effect was less marked at the lower altitude (16.0% O2) and did not
      occur during intermittent hypoxia (at both altitudes). The increased pPRL was
      significantly enhanced by restraint, restraint + hypoxia, hypoxia, and cold +
      hypoxia exposure. Treatment with a CRH R1 antagonist (CP-154,526) reversed
      hypoxia-decreased immunoreactive PRL and upregulated PRLmRNA in the pituitary.
      The data suggest that both CH and IH can stimulate rat PRL release in a time
      course- and intensity-dependent manner. However, compared to the relatively low
      CH-induced response, restraint induced a more powerful response than either cold
      or hypoxia alone. CRH R1 mediates PRL secretion and PRL mRNA expression in the
      pituitary under hypoxic exposure. Hypoxia-enhanced PRL response over the lifespan
      may play a significant role in adaptation to an extreme environment.

PMID- 16099462
TI  - Diagnosis and management of postpartum urinary retention.

PMID- 16099463
TI  - Group B streptococcus colonization in preterm labor and preterm premature rupture
      of membranes.

PMID- 16099464
TI  - Carotid atherosclerosis is associated with enhanced beta-chemokine levels in
      patients on continuous ambulatory peritoneal dialysis.
AB  - Increased oxidative stress (SOX) has been reported in continuous ambulatory
      peritoneal dialysis (CAPD) patients, but its influence on beta-chemokine levels
      and progression of atherosclerosis remains unknown. We determined three distinct
      SOX markers: Cu/Zn superoxide dismutase (Cu/Zn SOD), total peroxide and
      autoantibodies against oxidized LDL (OxLDL-Ab); high sensitivity C-reactive
      protein (hs CRP); beta-chemokines: monocyte chemoattractant protein-1 (CCL2),
      macrophage inflammatory proteins (CCL3 and CCL4) and regulated upon activation,
      normal T cell expressed and secreted (CCL5) and the intima-media thickness (IMT)
      values in CAPD patients both with and without cardiovascular disease (CVD) and
      healthy controls. CAPD patients both with and without CVD had significantly
      increased IMT (p<0.001 and <0.01), Cu/Zn SOD (both p<0.001) and CCL2 levels
      (p<0.001 and <0.01, respectively) as compared to controls. CCL4 (p<0.01) and hs
      CRP (p<0.05) were increased only in patients with CVD, whereas there were no
      differences in the total peroxide, OxLDL-Ab and CCL3 levels between patients and
      controls. CCL5 concentrations were significantly decreased in both patients
      subgroup (both p<0.001) versus controls. Multivariate analysis showed that age
      (p<0.001), male sex (p<0.01), CCL4 and CCL2 levels (both p<0.05) were the
      independent variables linked to IMT values. Our data suggest a possible role of
      enhanced beta-chemokine levels in the carotid atherosclerosis in patients treated
      with CAPD, in addition to age and male sex.

PMID- 16099465
TI  - Persistent liver expression of murine apoA-l using vectors based on adeno
      associated viral vectors serotypes 5 and 1.
AB  - Plasma levels of high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein
      A-l (apoA-l) are inversely related to risk for coronary heart disease.
      Overexpression of apoA-l inhibits atherosclerosis in animal models. A method of
      stably expressing apoA-l using somatic gene transfer would be of interest.
      Pseudotyped adeno-associated virus (AAV) vectors comprised of inverted terminal
      repeats from AAV serotype 2 have been used for liver-directed gene transfers. We
      hypothesized that liver-directed gene transfer of apoA-l using vectors based on
      AAV serotypes 1 and 5 would result in higher-level, prolonged expression of apoA
      l and increased HDL-C. To test this hypothesis we injected apoA-l-/- mice via the
      tail vein with either AAV2, AAV1 or AAV5 vectors encoding the murine apoA-l cDNA
      driven by the liver-specific thyroxine binding globulin promoter. Plasma levels
      of murine apoA-l and HDL-C were highest in mice injected with the AAV1-based
      vector and lowest in mice injected with the AAV2-based vector. Expression of apoA
      l was stable up to 1 year after vector injection. These results indicate that
      AAV5 and AAV1 are more effective vectors for achieving higher levels of stable
      transgene expression of apoA-l after liver-directed gene transfer than AAV2.
      Furthermore, AAV1-based vectors generate higher apoA-l levels than AAV5-based
      vectors. It is possible that the levels of expression achieved using these
      vectors will be therapeutic in preventing atherosclerosis.

PMID- 16099466
TI  - The use of scFv-displaying yeast in mammalian cell surface selections.
AB  - Yeast surface display has proven to be a powerful tool for the directed evolution
      of immunological proteins when soluble ligands are available (Cho, B.K., Kieke,
      M.C., Boder, E.T., Wittrup, K.D., Kranz, D.M., 1998. A yeast surface display
      system for the discovery of ligands that trigger cell activation. J. Immunol.
      Methods 220, 179; Boder, E.T., Midelfort, K.S., Wittrup, K.D., 2000. Directed
      evolution of antibody fragments with monovalent femtomolar antigen-binding
      affinity. Proc. Natl. Acad. Sci. U. S. A. 97, 10701; Shusta, E.V., Holler, P.D.,
      Kieke, M.C., Kranz, D.M., Wittrup, K.D., 2000. Directed evolution of a stable
      scaffold for T-cell receptor engineering. Nat. Biotechnol. 18, 754; Esteban, O.,
      Zhao, H., 2004. Directed evolution of soluble single-chain human class II MHC
      molecules. J. Mol. Biol. 340, 81). This investigation extends the utility of this
      display platform by demonstrating its capacity for use in cell panning
      selections. This was accomplished by employing a model single-chain antibody
      (scFv)-hapten system that allowed for detailed investigation of the factors
      governing panning success. Yeast displaying anti-fluorescein scFv (4-4-20)
      exhibited specific interactions with the fluoresceinated endothelial cells and
      could be recovered from large backgrounds of irrelevant yeast in just three
      rounds. Successful selections required as few as 1700 fluorescein ligands per
      cell, and a three-round enrichment ratio of 10(6) was possible. These results
      indicate that yeast surface display is a viable option for use in cell or tissue
      based selections.

PMID- 16099467
TI  - Reduced effectiveness of HMR 1098 in blocking cardiac sarcolemmal K(ATP) channels
      during metabolic stress.
AB  - ATP-sensitive K(+) (K(ATP)) channels are involved in ischemic cardioprotection
      induced by preconditioning (IPC), though the relative role of sarcolemmal
      (sK(ATP)) and mitochondrial (mitoK(ATP)) channels remains controversial. The
      sK(ATP)-selective sulphonylthiourea HMR 1098 has often been reported to be
      without effect on ischemic cardioprotection, suggesting minimal involvement of
      sK(ATP). Since some sulphonylureas show reduced potency under conditions of
      metabolic stress, we used patch clamp to assess the ability of HMR 1098 to block
      sK(ATP) currents of adult rat ventricular myocytes activated by metabolic
      inhibition (MI, NaCN+iodoacetate). In contrast to the prototype sulphonylurea
      glibenclamide, HMR 1098 (10 muM) was without effect on sK(ATP) currents, and also
      did not inhibit MI-induced action potential shortening. However, HMR 1098 blocked
      sK(ATP) current induced by the K(ATP) opener pinacidil (IC(50)=0.36+/-0.02 muM),
      and reversed pinacidil-induced action potential shortening. In inside-out
      patches, block by HMR 1098 was relieved by increasing MgADP concentrations (1-100
      muM). HMR 1098 inhibited pinacidil-activated recombinant Kir6.2/SUR2A channels
      with a similar IC(50) (0.30+/-0.04 muM), but was less effective when channels
      were activated by low intracellular ATP. HMR 1098 displaced binding of the
      pinacidil analogue [(3)H]P1075 to native cardiac membranes with a biphasic
      inhibition curve. Our results show that HMR 1098 becomes a much less effective
      inhibitor of sK(ATP) during metabolic stress, and suggest that the lack of effect
      of HMR 1098 on ischemic cardioprotection reported in some studies may represent
      loss of block by the drug under these conditions rather than a lack of
      involvement of sK(ATP) channels.

PMID- 16099468
TI  - A negative feedback mechanism involving nitric oxide and nuclear factor kappa-B
      modulates endothelial nitric oxide synthase transcription.
AB  - Nuclear factor kappa B (NFkappaB), commonly a proinflammatory transcription
      factor, is responsible for increasing transcription of the endothelial cell
      nitric oxide synthase (eNOS) in response to laminar shear stress. Nitric oxide
      (NO) production can be stimulated by shear, and NO is known to inhibit NFkappaB
      activation. We hypothesized that this inhibitory action of NO on NFkappaB
      activation serves as a negative feedback to inhibit NFkappaB activity and eNOS
      transcription. Exposure of bovine aortic endothelial cells to laminar shear
      stimulated steady state eNOS mRNA expression and eNOS promoter activity as
      measured using an eNOS promoter/CAT construct. These effects of shear were
      enhanced by the NOS inhibitor l-NAME and decreased by the NO-donor DPTA-NO by 30
      50%. The NFkappaB inhibitor panepoxydone prevented the increase in eNOS mRNA
      caused by shear confirming a role of NFkappaB in this response. Shear stress
      stimulated a transient (30 min) nuclear translocation of the NFkappaB subunit
      p50. Treatment with l-NAME increased binding of the NFkappaB subunit p50 to
      consensus oligonucleotide-coated microtiter plates, while having only minimal
      effect on binding of p65, strongly suggesting that nitric oxide mainly inhibits
      p50 activation. Using the biotin switch method, we found that shear stress
      stimulates p50 nitrosylation and this was prevented by l-NAME. Moreover,
      transfection of endothelial cells with a vector encoding the C62S p50, a variant
      with a point mutation of the nitrosylation site C62, markedly increased nuclear
      translocation of p50 and doubled eNOS mRNA expression under shear stress compared
      to that observed in cells transfected with wild-type p50. We conclude that this
      interaction between shear, NFkappaB activation, NO production and NFkappaB
      inhibition represents a classical negative feedback loop, which prevents
      sustained activation of NFkappaB. In the absence of NO, shear stimulation of
      NFkappaB and eNOS transcription are enhanced. Our findings emphasize the critical
      role of NO in modulation of the endothelial cell inflammatory state. Several
      common diseases, including hypercholesteremia, hypertension and diabetes, are
      associated with eNOS dysfunction. Under these conditions, decreased NO
      availability may result in sustained activation of NFkappaB in response to shear
      and unrestrained endothelial inflammation.

PMID- 16099469
TI  - Preconditioning effects of PKCdelta.

PMID- 16099471
TI  - Kynurenine metabolism in plasma and in red blood cells in Parkinson's disease.
AB  - Substantial evidence indicates that neuroactive kynurenine metabolites play a
      role in the normal physiology of the human brain, and are involved in the
      pathology of neurodegenerative disorders such as Parkinson's disease (PD). A
      sidearm product of the pathway, kynurenic acid (KYNA), which is synthesized by
      the irreversible transamination of kynurenine (KYN) by kynurenine
      aminotransferases (KAT I and KAT II), is an excitatory amino acid receptor
      antagonist. In the present study we measured the level of KYNA and the activities
      of the biosynthetic enzyme isoforms KAT I and KAT II in the plasma and in the
      erythrocytes (RBC) of 19 PD patients and 17 age-matched controls. The KAT I and
      KAT II activities were significantly lower in the plasma of PD patients, followed
      by a tendency to a decrease in plasma KYNA. An elevated KYNA level correlated
      with a significant increase in KAT II activity in the RBC of PD patients. These
      data support the contribution of an altered KYNA metabolism in the RBC to the
      pathogenesis of PD. The increased activity of KAT II in correlation with the
      elevated KYNA level in the RBC may mediate a consecutive protective response
      against excitatory neurotoxic effects.

PMID- 16099470
TI  - Transgenic overexpression of SUR1 in the heart suppresses sarcolemmal K(ATP).
AB  - The lack of pathological consequences of cardiac ATP-sensitive potassium channel
      (K(ATP)) channel gene manipulation is in stark contrast to the effect of similar
      perturbations in the pancreatic beta-cell. Because the pancreatic and cardiac
      channel share the same pore-forming subunit (Kir6.2), the different effects of
      genetic manipulation likely reflect, at least in part, the tissue-specific
      expression of the regulatory subunit (SUR1 in pancreas vs. SUR2A in heart) of the
      bipartite channel complex. To examine this, we have generated transgenic (TG)
      mice that overexpress epitope-tagged SUR1 or SUR2A under the transcriptional
      control of the alpha-myosin heavy chain promoter. Western blot and real time RT
      PCR analysis confirm transgene expression in the heart, and variable levels of
      SUR1 RNA and protein, in 16 viable founder lines. Surprisingly, activation of
      channels by either pharmacological agents (diazoxide and pinacidil) or metabolic
      inhibitors (oligomycin and 2-deoxyglucose) reveals a suppression of total K(ATP)
      conductance in high expressing TG mice. Moreover, K(ATP) channel activity was
      significantly reduced in excised cardiac patches from TG myocytes that
      overexpress either SUR1 or SUR2A. Using a recombinant cell system, we show that
      overexpression of either SUR1 or Kir6.2 suppresses the functional expression of
      K(ATP) from optimized dimeric SUR1-Kir6.2. Thus, the graded effect of SUR1
      expression in the intact heart appears to demonstrate an in vivo requirement for
      1:1 expression ratio of Kir6.2 and SURx.

PMID- 16099472
TI  - A model of event-related EEG synchronization changes in beta and gamma frequency
      bands.
AB  - During preparation, execution and recovery from simple movements, the EEG power
      spectrum undergoes a sequence of changes. The power in the beta band (13-25 Hz)
      decreases during preparation and execution of movement, but during recovery it
      reaches a level higher than that in the reference period (not affected by the
      event). These effects are known as event-related beta desynchronization and beta
      rebound. The power in the gamma band (>30 Hz) increases significantly just before
      the onset of the movement. This effect is known as event-related gamma
      synchronization. There are numerous observations concerning these effects but the
      underlying physiological mechanisms and functional role are not clear. We propose
      a lumped computational model of a cortical circuit. The model consists only of a
      pyramidal and an interneuronal population. Each population represents averaged
      properties of constituting neurons. The output of the model represents a local
      field potential, with a power spectrum peak either in the beta or in the gamma
      band. The model elucidates the mechanisms of transition between slower and faster
      rhythms, gamma synchronization and beta desynchronization and rebound effects.
      The sufficient conditions to observe the effects in the model are changes of the
      external excitation level and of the connection strength between excitatory and
      inhibitory populations attributed to short-time plasticity. The present model
      presents the role of the pyramidal neurons to interneuron connection in the
      oscillatory behavior of the two populations. We conclude that the pronounced
      facilitation of the pyramidal to fast spiking interneuron connections, initiated
      by robust excitation of the motor cortex neurons, may be essential for the effect
      of beta rebound. Further experiments concerning short-time plasticity during
      behavioral tasks would be of great value in studies of functional local cortical
      circuits.

PMID- 16099473
TI  - Methods and interpretation of coral recruitment studies: effects of anthropogenic
      disturbance?

PMID- 16099474
TI  - Heavy metal concentrations in sediment, benthic invertebrates and fish in three
      salt marsh areas subjected to different pollution loads in the Tagus Estuary
      (Portugal).

PMID- 16099475
TI  - Influence of the reproductive cycle on cytochrome P450 levels in the sea star
      Coscinasterias muricata.

PMID- 16099476
TI  - Distribution of monomethylmercury and mercury in surface sediments of the Tagus
      Estuary (Portugal).

PMID- 16099477
TI  - Accumulation of lipid peroxidation-derived DNA lesions: potential lead markers
      for chemoprevention of inflammation-driven malignancies.
AB  - Chronic inflammatory processes produce an excess of ROS and DNA-reactive
      aldehydes from lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal (HNE)
      and malondialdehyde (MDA), which can modify cellular macromolecules and drive to
      malignancy. Etheno-modified DNA bases are generated inter alia by reaction of DNA
      with the major LPO product, HNE. We are investigating steady-state levels of
      etheno-DNA adducts in organs with diseases related to persistent inflammatory
      processes that can lead to malignancies. We have developed ultrasensitive and
      specific methods for the detection of etheno-DNA base adducts in human tissues
      and in urine. Etheno-DNA adduct levels were found to be significantly elevated in
      the affected organs of subjects with chronic pancreatitis, ulcerative colitis and
      Crohn's disease. When patients with alcohol abuse-related hepatitis, fatty liver,
      fibrosis and cirrhosis were compared with asymptomatic livers, excess hepatic DNA
      damage was seen in the three latter patient groups. Etheno-deoxyadenosine
      excreted in urine was measured in HBV-infected patients diagnosed with chronic
      hepatitis, cirrhosis and hepatocellular carcinoma. As compared to controls, these
      patients had up to 90-fold increased urinary levels. Impaired or imbalanced DNA
      repair pathways may influence the steady-state levels of etheno-DNA adducts in
      inflamed tissues. In conclusion, etheno-DNA adducts may serve as potential lead
      markers for assessing progression of inflammatory cancer-prone diseases. If so,
      the efficacy of human chemopreventive interventions for malignant disease
      prevention could be verified.

PMID- 16099478
TI  - The impact of plasma folate levels of mothers and newborns on intrauterine growth
      retardation and birth weight.
AB  - Folate plays an important role in the genomic stability of human cells. In our
      studies of the impact of environmental pollution on human health, we have found
      that air pollution can affect pregnancy outcome. As it may be also affected by
      nutrition, we examined the effect of plasma folate levels of mothers and newborns
      on intrauterine growth retardation (IUGR) and birth weight (BW) in cohorts from
      Prague (N=319) and Teplice (N=444). The lower plasma levels (<6.1 nmol/L) were
      observed in 7.1% of mothers in Prague, and in 9.6% of mothers in Teplice. The
      higher plasma levels (>36.5 nmol/L) were observed in 28.4% of mothers in Prague,
      and in 15.7% of mothers in Teplice. The higher plasma levels were observed in
      75.4% of newborns in Prague, and 73.2% of newborns in Teplice. When comparing
      maternal high versus low folate plasma levels and IUGR by logistic regression,
      the risk of IUGR was significantly decreased for European cohort (according to
      ethnicity) with gestation age >36 weeks [N=536, OR=0.44, P=0.026], and even more
      pronounced in the group of European smokers [N=157, OR=0.14, P=0.015]. Using
      multiple regression analysis, plasma folate levels of mothers and newborns
      significantly affected the birth weight of newborns of smoking mothers (P<0.05).
      The obtained results seem to indicate a positive effect of folate on pregnancy
      outcome, especially its potential to decrease the risk of IUGR in European
      population and lower birth weight in smoking European mothers. It would be
      warranted to study the effect of folate levels on pregnancy outcomes in the
      relationship to different environmental pollution and life styles of mothers.

PMID- 16099479
TI  - Molecular chemoprevention by selenium: a genomic approach.
AB  - Basic research and clinical chemoprevention trials support the protective role of
      selenium in cancer prevention but the mechanisms based on the molecular level
      remain to be fully defined. This mini-review focuses only on the elucidation of
      the molecular mechanisms of cancer prevention by selenium using the genomics
      approach; target organs discussed here are breast, prostate, colon and lung. The
      results described here support the utility of microarray technology in
      delineating the molecular mechanisms of cancer prevention by selenium. These
      results are based on studies employing human and rodent cell lines and tissues
      from animal models ranging from normal to frank cancer. The dose and the form of
      selenium are determining factors in cancer chemoprevention. The results of the
      microarray analysis reviewed here indicate that selenium, independent of its form
      and the target organ examined, alters several genes in a manner that can account
      for cancer prevention. Selenium can up regulate genes related to phase II
      detoxification enzymes, certain selenium-binding proteins and select apoptotic
      genes, while down regulating those related to phase I activating enzymes and cell
      proliferation. Independent of tissue type, selenium arrests cells in G1 phase of
      cell cycle, inhibits CYCLIN A, CYCLIN D1, CDC25A, CDK4, PCNA and E2F gene
      expressions while induces the expressions of P19, P21, P53, GST, SOD, NQO1,
      GADD153 and certain CASPASES. In addition to those described above, genes such as
      OPN, which is mainly involved in metastasis and recently reported to be down
      regulated by selenium, should be considered as potential molecular marker in
      clinical chemoprevention trials. Collectively, literature data indicate that some
      of these genes that were altered by selenium are also involved in the development
      of human cancers described in this review. It appears that androgen receptor
      status may influence the effect of selenium on gene expression profile in
      prostate cancer; whether estrogen receptor may influence the effect of selenium
      on gene expression in breast cancer requires further studies. Knowledge from gene
      array data in combination with proteomics approaches, using homogenous population
      of cell types with the aid of laser capture microdissection, may provide an
      individualized dimension of information on cancer risk and potential targets for
      its prevention. The molecular (genetic) biomarkers presented in this review will
      provide the foundation for future studies of the chemopreventive properties of
      structurally varied selenium compounds.

PMID- 16099480
TI  - Coffee consumption induces GSTP in plasma and protects lymphocytes against (+/-)
      anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide induced DNA-damage: results of
      controlled human intervention trials.
AB  - A number of animal studies indicate that coffee protects against chemical
      induction of cancer; also human studies suggest that coffee consumption is
      inversely related with the incidence of different forms of cancer. The protective
      effects were attributed to induction of glutathione-S-transferases (GSTs) and aim
      of the present human study was to find out if coffee causes induction of GSTs and
      protects against DNA-damage caused by (+/-)-anti-B[a]P-7,8-dihydrodiol-9,10
      epoxide (BPDE), the DNA-reactive metabolite of benzo(a)pyrene. Ten participants
      consumed 1L unfiltered coffee/d over 5 days. Before and after the intervention,
      saliva and blood were collected and the overall GST activity was measured with 1
      chloro-2,4-dinitrobenzene (CDNB). Additionally, GSTP and GSTA were determined in
      plasma with immunoassays. In blood, only weak (p=0.042) induction of GST (CDNB)
      was found. Furthermore, pronounced (three-fold) induction of GSTP was observed in
      blood, whereas GSTA was not altered. No correlations were seen between induction
      of GST (CDNB) and GSTP activities and the GSTP1 genotypes of the participants.
      Also clinical parameters (creatinine, alanine, aminotransferase, aspartate
      aminotransferase, alkaline phosphatase), which are markers for organ damage, were
      monitored. None of them was altered by coffee, but serum cholesterol levels were
      slightly (not significantly) enhanced. In a second trial (n=7), GSTP induction by
      unfiltered and paper filtered coffees, differing in cafestol and kahweol
      contents, were compared. The participants consumed 1L coffee/d over 3 days. Again
      significant (three-fold) induction of GSTP was observed. The effects seen with
      the two coffees were identical, indicating that the diterpenoid concentrations
      are not responsible for the effects. In a further trial (n=7), the effect of
      coffee (unfiltered, 1L/d, 5 days) on BPDE induced DNA-migration was studied in
      comet assays. A 45% reduction effect was observed. Our findings show that coffee
      induces GSTP in humans and indicate that consumption may lead to protection
      towards polycyclic aromatic hydrocarbons.

PMID- 16099481
TI  - The effects of chronic unpredictable stress on male rats in the water maze.
AB  - Exposure to chronic stress can affect cognitive processes in a complex manner
      depending upon the intensity and duration of the stressors. The current study
      investigated the effects of chronic unpredictable stress (CUS), a procedure
      thought to use moderate stressors, on acquisition of and performance in the
      Morris Water Maze (MWM). Separate behavioral tests were also used to determine
      whether the stress-induced changes in MWM were due to general changes in
      locomotor activity or preference for a rewarding stimulus. Adult male rats were
      exposed to 10 days of different stressors applied at various times. Following the
      last stressor, stressed and non-stressed rats began training in the MWM, were
      tested in an open field box, or were tested for sucrose preference. In the MWM,
      rats exposed to stress had shorter latencies to reach the hidden platform during
      training. The path lengths on day 2 of training, trials 2 and 4, were shorter in
      CUS rats compared to controls, with the stressed rats traveling less in the outer
      portion of the maze. During the probe trial, CUS rats also traveled less overall
      and less in the outer portion of the maze, although all other measures were the
      same. The facilitation in learning the platform location was not due to a change
      in other behavioral components that could contribute to the measures, such as
      general activity, sensorimotor processing or the preference for a 2% sucrose
      solution. Thus, chronic unpredictable stress selectively appears to affect the
      search strategies in the water maze.

PMID- 16099482
TI  - Neonatal handling increases fear and aggression in lactating rats.
AB  - Neonatal handling reduces fear in male and cycling female rats, but increases
      maternal aggressive behavior against intruders to the nest area. Present study
      aimed to analyze the effects of neonatal handling on the maternal aggressive
      behavior and the activity in the open field with a predator of lactating rats on
      the 8th and the 18th postpartum days (periods of high and low aggressiveness). As
      pups, animals were divided into two groups: nonhandled (no neonatal manipulation)
      and handled (handling for 1 min during the first 10 days after delivery). As
      adults, females of both groups were impregnated and tested against a male
      intruder for aggressive behavior and in the open field with a cat inside a wire
      meshed cage. Results showed that on the 8th day frequency of aggressive behaviors
      of handled females was higher than that of the nonhandled ones, but on the 18th
      day, no significant difference was detected. Surprisingly, in the open field
      test, handled females showed decreased locomotion and increased freezing on the
      8th day compared to the nonhandled ones. The opposite relationship between
      increased aggressiveness with reduced fear is observed in the nonhandled control
      females in early and late lactation periods. However, neonatal handling abolishes
      this relationship. Apparently, the increased aggressiveness in neonatal handled
      lactating females does not depend on a decrease in fear. Our findings support the
      hypothesis that long lasting effects of early life stimulation is a dynamic
      function depending on the behavioral system and the period of life analyzed.
      Moreover, they caution the relationship between aggressive behavior and fear.

PMID- 16099483
TI  - Aluminum mediates compositional alterations of polar lipid classes in maize
      seedlings.
AB  - Changes in lipid composition were investigated on maize roots and shoots under
      aluminum stress. After 4d exposure to 100 microM Al, root growth was inhibited
      while shoot growth was not affected. In roots, the decrease of the DBI (double
      bond index) of total fatty acids may signal a decrease in membrane fluidity. The
      total lipids (TL) decreased by 49%, but phospholipids (PL), phosphatidylcholine
      (PC) and phosphatidylinositol (PI) increased to approximately 3-fold. The MGDG
      increased to 2-fold but no significant change was found in the DGDG. The steryl
      lipids (SL) increased by 69%. The SL/PL ratio decreased from 2.64 to 1.52 and the
      MGDG/DGDG ratio increased from 0.45 to 1.06 in roots of Al-stressed plants. Al
      leads to oxidative stress in roots of treated plants as indicated by the increase
      of malondialdehyde (MDA) concentrations. In shoots, changes in fatty acid
      composition were associated with an increase of the DBI in all lipid classes
      except that of the DGDG decreased. The PG was the lipid class which shows the
      large variation of fatty acid composition. No significant changes were found
      either for TL, PL, SL or MDA concentrations in shoots of Al-treated plants. While
      PE levels did not show significant change, PI and PG increased and PC decreased.
      However, the Al caused 87% decrease in the GL levels. The MGDG and DGDG decreased
      to 19- and 8-fold, respectively. The deleterious effects of Al on polar lipids
      could be caused by a direct intervention of Al on plasma membrane and/or
      alteration of cell metabolism.

PMID- 16099484
TI  - Beta-cyclolavandulyl and beta-isocyclolavandulyl esters from Peucedanum
      paniculatum L., an endemic species to Corsica.
AB  - Eight cyclolavandulyl esters (beta-cyclolavandulyl and beta-isocyclolavandulyl
      acetate, propionate, isobutyrate, isovalerate) were identified in the leaf and
      root oils of Peucedanum paniculatum L., an endemic species to Corsica, by
      comparison of their spectroscopic data with those of synthetic material. Their
      structures were elucidated by spectroscopic methods. The antimicrobial activity
      of essential oils of leaves and roots was evaluated against eleven
      microorganisms.

PMID- 16099485
TI  - Isolation of an N-acetyl-D-glucosamine specific lectin from the rhizomes of
      Arundo donax with antiproliferative activity.
AB  - A lectin with antiproliferative activity towards human cancer cell lines and
      mitogenic towards human peripheral blood mononuclear cells was purified from the
      rhizomes of Arundo donax (Linn.) by affinity chromatography on N-acetyl-d
      glucosamine linked to epoxy-activated sepharose-6B. The pure preparation
      apparently yielded a single band of approximately 15 kDa on SDS-PAGE, pH 8.3,
      under both reducing and non-reducing conditions. The molecular mass of native
      lectin was 32 kDa as determined by gel filtration chromatography. This showed the
      lectin to be a dimer, with subunits not held together by disulphide linkages. The
      A. donax lectin (ADL) agglutinated rabbit erythrocytes and the agglutination was
      inhibited by N-acetyl-d-glucosamine and its di- and trimer. The lectin was
      thermostable upto 55 degrees C and showed optimum activity in the range of pH 7.0
      9.0 and comprised of 2.1% carbohydrate content.

PMID- 16099486
TI  - Characterization in vitro and in vivo of the putative multigene 4-coumarate:CoA
      ligase network in Arabidopsis: syringyl lignin and sinapate/sinapyl alcohol
      derivative formation.
AB  - A recent in silico analysis revealed that the Arabidopsis genome has 14 genes
      annotated as putative 4-coumarate:CoA ligase isoforms or homologues. Of these, 11
      were selected for detailed functional analysis in vitro, using all known possible
      phenylpropanoid pathway intermediates (p-coumaric, caffeic, ferulic, 5
      hydroxyferulic and sinapic acids), as well as cinnamic acid. Of the 11
      recombinant proteins so obtained, four were catalytically active in vitro, with
      fairly broad substrate specificities, confirming that the 4CL gene family in
      Arabidopsis has only four members. This finding is in agreement with our previous
      phylogenetic analyses, and again illustrates the need for comprehensive
      characterization of all putative 4CLs, rather than piecemeal analysis of selected
      gene members. All 11 proteins were expressed with a C-terminal His6-tag and
      functionally characterized, with one, At4CL1, expressed in native form for
      kinetic property comparisons. Of the 11 putative His6-tagged 4CLs, isoform At4CL1
      best utilized p-coumaric, caffeic, ferulic and 5-hydroxyferulic acids as
      substrates, whereas At4CL2 readily transformed p-coumaric and caffeic acids into
      the corresponding CoA esters, while ferulic and 5-hydroxyferulic acids were
      converted quite poorly. At4CL3 also displayed broad substrate specificity
      efficiently converting p-coumaric, caffeic and ferulic acids into their CoA
      esters, whereas 5-hydroxyferulic acid was not as effectively utilized. By
      contrast, while At4CL5 is the only isoform capable of ligating sinapic acid, the
      two preferred substrates were 5-hydroxyferulic and caffeic acids. Indeed, both
      At4CL1 and At4CL5 most effectively utilized 5-hydroxyferulic acid with kenz
      approximately 10-fold higher than that for At4CL2 and At4CL3. The remaining seven
      4CL-like homologues had no measurable catalytic activity (at approximately 100
      microg protein concentrations), again bringing into sharp focus both the
      advantages to, and the limitations of, current database annotations, and the need
      to unambiguously demonstrate true enzyme function. Lastly, although At4CL5 is
      able to convert both 5-hydroxyferulic and sinapic acids into the corresponding
      CoA esters, the physiological significance of the latter observation in vitro was
      in question, i.e. particularly since other 4CL isoforms can effectively convert 5
      hydroxyferulic acid into 5-hydroxyferuloyl CoA. Hence, homozygous lines
      containing T-DNA or enhancer trap inserts (knockouts) for 4cl5 were selected by
      screening, with Arabidopsis stem sections from each mutant line subjected to
      detailed analyses for both lignin monomeric compositions and contents, and
      sinapate/sinapyl alcohol derivative formation, at different stages of growth and
      development until maturation. The data so obtained revealed that this "knockout"
      had no significant effect on either lignin content or monomeric composition, or
      on the accumulation of sinapate/sinapyl alcohol derivatives. The results from the
      present study indicate that formation of syringyl lignins and sinapate/sinapyl
      alcohol derivatives result primarily from methylation of 5-hydroxyferuloyl CoA or
      derivatives thereof rather than sinapic acid ligation. That is, no specific
      physiological role for At4CL5 in direct sinapic acid CoA ligation could be
      identified. How the putative overlapping 4CL metabolic networks are in fact
      organized in planta at various stages of growth and development will be the
      subject of future inquiry.

PMID- 16099487
TI  - Falciparum malaria after splenectomy: a prospective controlled study of 33
      previously splenectomized Malawian adults.
AB  - We identified 33 Malawians who had undergone total splenectomy for traumatic
      injury. We reviewed these and 33 controls by clinical and parasitological
      examination monthly for 1 year. Splenectomized patients (S) were 2.5 times as
      likely as controls (C) to complain about febrile symptoms during the month
      preceding a visit (P < 0.0001). They were nearly twice as likely as controls to
      have Plasmodium falciparum parasitaemia (S: 176/283 person visits; C: 86/262; P <
      0.0001). Parasitaemia was more likely to be associated with febrile symptoms in
      splenectomized individuals (S: 104/176, 59%; C: 24/86, 28%; P < 0.0001). There
      were three deaths (two non-malarial, one unexplained) among splenectomized
      subjects and none in the control group. Parasite densities reached significantly
      higher levels, and mature parasite stages were more often seen in the peripheral
      blood, in asplenic individuals. In a partially immune population, asplenic
      individuals are at increased risk of malarial infections and illness. In a larger
      group without the benefit of regular review and prompt therapy, there may be an
      increased risk of life-threatening malaria. Splenectomy should be avoided when
      possible in an area with endemic transmission of P. falciparum.

PMID- 16099488
TI  - Risk factors associated with typhoid fever in Son La province, northern Vietnam.
AB  - Between July and December 2002, we undertook a hospital-based case-control study
      to identify risk factors associated with typhoid fever in Son La province,
      northern Vietnam. Among 617 suspected cases, 90 cases of typhoid fever were
      confirmed by blood or stool culture. One hundred and eighty controls (neighbours
      of typhoid cases matched for gender and age) were chosen. Participants were
      interviewed at home using a standardized questionnaire. Seventy-five per cent of
      cases were aged 10-44 years. No cases in patients aged less than 5 years were
      recorded in this study. In a conditional logistic regression analysis recent
      contact with a typhoid patient (OR = 3.3, 95% CI 1.7-6.2, P < 0.001), no
      education (OR = 2.0, 95% CI 1.0-3.7, P = 0.03) and drinking untreated water (OR =
      3.9, 95% CI 2.0-7.5, P < 0.001) were independently associated with typhoid fever.
      Improving quality of drinking water must be a priority and health education
      strategies targeted at individuals with no schooling, and contacts of patients,
      would be expected to decrease the burden of typhoid fever.

PMID- 16099489
TI  - Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy
      in aryl hydrocarbon receptor (AhR) null mice.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      characterized to play a role in detection and adaptation to environmental
      stimuli. Genetic deletion of AhR results in hypertension, and cardiac hypertrophy
      and fibrosis, associated with elevated plasma angiotensin II (Ang II) and
      endothelin-1 (ET-1), thus AhR appears to contribute to cardiovascular
      homeostasis. In these studies, we tested the hypothesis that ET-1 mediates
      cardiovascular pathology in AhR null mice via ETA receptor activation. First, we
      determine the time courses of cardiac hypertrophy, and of plasma and tissue ET-1
      expression in AhR wildtype and null mice. AhR null mice exhibited increases in
      heart-to-body weight ratio and age-related expression of cardiac hypertrophy
      markers, beta-myosin heavy chain (beta-MHC), and atrial natriuretic factor (ANF),
      which were significant at 2 months. Similarly, plasma and tissue ET-1 expression
      was significantly elevated at 2 months and increased further with age. Second,
      AhR null mice were treated with ETA receptor antagonist, BQ-123 (100
      nmol/kg/day), for 7, 28, or 58 days and blood pressure, cardiac fibrosis, and
      cardiac hypertrophy assessed, respectively. BQ-123 for 7 days significantly
      reduced mean arterial pressure in conscious, catheterized mice. BQ-123 for 28
      days significantly reduced the histological appearance of cardiac fibrosis.
      Treatment for 58 days significantly reduced cardiac mass, assessed by heart
      weight, echocardiography, and beta-MHC and ANF expression; and reduced cardiac
      fibrosis as determined by osteopontin and collagen I mRNA expression. These
      findings establish ET-1 and the ETA receptor as primary determinants of
      hypertension and cardiac pathology in AhR null mice.

PMID- 16099490
TI  - Contributions from lateral interaction mechanisms to the human ERG can be studied
      with a two-frequency method.
AB  - We present a two-frequency method to investigate lateral interaction components
      (liERGs) in the human electroretinogram. Adjacent half cycles of sinusoidal
      gratings were modulated sinusoidally with different temporal frequencies f1 and
      f2. The liERGs were defined by the Fourier components at the intermodulation
      frequencies /f1 - f2/ and f1 + f2 which indicate nonlinear interactions between
      the half cycles. Significant liERGs were found in all subjects with a monotonic
      increase of the liERG magnitude in the spatial frequency range from f(s)=0.07 to
      2.4 cpd. When /f1 - f2/ was below 5 Hz, liERGs were masked by noise intrusions.
      In a control experiment we demonstrated that the liERGs were not evoked by stray
      light artifacts. The liERGs may help to further differentiate the responses that
      are evoked by patterned stimuli within the retina.

PMID- 16099491
TI  - Opinions and research priorities.

PMID- 16099492
TI  - The importance of housing conditions on behavioral sensitization and tolerance to
      ethanol.
AB  - The differential outcomes of social isolation and crowding environment on the
      effects of single or repeated administration of ethanol on open-field behavior
      were examined in female mice. Whereas housing conditions did not alter the
      increase in locomotor activity induced by ethanol single administration,
      behavioral sensitization (a progressive increase of a drug effect following
      repeated drug administration) to the locomotor activating effect of ethanol was
      significantly greater in crowded mice as compared to isolated and control groups.
      Single administration of ethanol significantly decreased rearing frequency and
      increased immobility duration, there being tolerance to these ethanol behavior
      effects after repeated treatment. Social isolation attenuated the increase in
      immobility behavior induced by single administration of ethanol and potentiated
      the tolerance of ethanol-induced rearing decrease, verified after repeated
      treatment. These results point out that both sensitization and tolerance to the
      behavioral effects of ethanol can be critically influenced by housing conditions.

PMID- 16099493
TI  - Priming nouns and verbs: differential influences of semantic and grammatical cues
      in the two cerebral hemispheres.
AB  - The current experiment investigated how sentential form-class expectancies
      influenced lexical-semantic priming within each hemisphere. Sentences were
      presented that led readers to expect a noun or a verb and the sentence-final
      target word was presented to one visual field/hemisphere for a lexical decision
      response. Noun and verb targets in the semantically related condition were
      compared to an unrelated prime condition, which also predicted part of speech but
      did not contain any lexical-semantic associates of the target word. The semantic
      priming effect was strongly modulated by form-class expectancy for RVF/LH
      targets, for both nouns and verbs. In the LVF/RH, semantic priming was obtained
      in all conditions, regardless of whether the form-class expectancy was violated.
      However, the nouns that were preceded by a noun-predicting sentence showed an
      extremely high priming value in the LVF/RH, suggesting that the RH may have some
      sensitivity to grammatical predictions for nouns. Comparisons of LVF/RH priming
      to calculations derived from the LSA model of language representation, which does
      not utilize word order, suggested that the RH might derive message-level meaning
      primarily from lexical-semantic relatedness.

PMID- 16099494
TI  - Effects of dialect on merger perception: ERP and behavioral correlates.
AB  - Native speakers of a language are often unable to consciously perceive, and have
      altered neural responses to, phonemic contrasts not present in their language.
      This study examined whether speakers of dialects of the same language with
      different phoneme inventories also show measurably different neural responses to
      contrasts not present in their dialect. Speakers with (n=11) and without (n=11)
      an American English I/E (pin/pen) vowel merger in speech production were asked to
      discriminate perceptually between minimal pairs of words that contrasted in the
      critical vowel merger and minimal pairs of control words while their event
      related potential (ERPs) were recorded. Compared with unmerged dialect speakers,
      merged dialect speakers were less able to make behavioral discriminations and
      exhibited a reduced late positive ERP component (LPC) effect to incongruent
      merger vowel stimuli. These results indicate that between dialects of a single
      language, the behavioral response differences may reflect neural differences
      related to conscious phonological decision processes.

PMID- 16099495
TI  - Superoxide dismutases and their impact upon human health.
AB  - Superoxide dismutases (SOD), a group of metal-containing enzymes, have a vital
      anti-oxidant role in human health, conferred by their scavenging of one of the
      reactive oxygen species, superoxide anion. Three types of SODs are known in
      humans, with the most abundant being cytosolic SOD1, identified by its Cu, Zn
      containing prosthetic group. The presence of these metals and the coordination to
      certain amino acids are essential for function. SODs are among the first line of
      defense in the detoxification of products resulting from oxidative stress. Here,
      we describe the importance of SOD function, and the need for coordination with
      other ROS-scavenging enzymes in this pathway of detoxification. The impact of
      metal-deficient diets (copper or zinc) or incorrect metal ion incorporation
      (copper chaperone for SOD) onto nascent SOD, are also examined. Finally, human
      pathologies associated with either SOD dysfunction or decreased activity are
      discussed with current progress on the development of novel therapies.

PMID- 16099496
TI  - Non-biofouling materials prepared by atom transfer radical polymerization
      grafting of 2-methacryloloxyethyl phosphorylcholine: separate effects of graft
      density and chain length on protein repulsion.
AB  - Biomimetic poly(2-methacryloyloxyethyl phosphorylcholine) (poly(MPC)) brushes
      with graft density 0.06-0.39 chains/nm2 and chain length 5-200 monomer units were
      prepared from silicon wafer surfaces by combining self-assembly of initiator and
      surface-initiated atom transfer radical polymerization (ATRP). Water contact
      angle, X-ray photoelectron spectroscopy, and atomic force microscopy were used to
      characterize the modified surfaces. These surfaces with well-controlled poly(MPC)
      brushes were tested for protein repelling performance. Fibrinogen adsorption from
      tris-buffered saline at pH 7.4 decreased significantly with increasing graft
      density and/or chain length of poly(MPC) and reached a level of < 10 ng/cm2 at
      graft density > or = 0.29 chains/nm2 and chain length > or = 100 units, compared
      to ca. 570 ng/cm2 for the unmodified samples. While the fibrinogen adsorption was
      determined by both graft density and chain length, it showed a stronger
      dependence on graft density than on chain length.

PMID- 16099497
TI  - The effect of epsilon-caproyl/D,L-lactyl unit composition on the hydrolytic
      degradation of poly(D,L-lactide-ran-epsilon-caprolactone)-poly(ethylene glycol)
      poly(D,L-lactide-ran-epsilon-caprolactone).
AB  - The degradation of P(DLAX-ran-CLY)-b-PEG-b-P(DLAX-ran-CLY)s ( P(DLAX-ran-CLY):
      Poly(D,L-lactide-ran-epsilon-caprolactone), PEG: Poly(ethylene glycol), X: D,L
      lactyl unit fraction, Y: epsilon-caproyl unit fraction) is investigated. The
      fraction of DLA in the both end blocks is varied while the overall molecular
      weight and molecular weight of PEG are kept constant. DSC, XRD and GPC are
      employed to track the degradation process up to 200 days. Also the change in the
      surface and cross-sectional morphology is provided by SEM micro-photographs. The
      result of water absorption and weight loss characterization reveals that the
      incorporation of DLA in the polyester block could be an effective tool to
      facilitate degradation as well as water absorption. By tracking the change of
      molecular weight and polydispersity, chain scission and transport or removal of
      degraded product from the specimen were found to play a complex role in overall
      degradation.

PMID- 16099498
TI  - Mouse embryonic stem cell colonisation of carbonated apatite surfaces.
AB  - Apatites play a crucial role in the body and have been used extensively in
      biomedical implants. The influence on stem cell behaviour is not known and so
      this study will explore whether sintered carbonated apatites are favourable for
      propagation of stem cells. Different weight substitutions of carbonated apatite,
      specifically 2.5 wt% (2.5 wt%CAP) and 5 wt% (5 wt%CAP), were sintered and
      characterised prior to the investigation of their potential as a matrix for the
      support of mouse embryonic stem (ES) cells. Characterisation of the apatites
      included elemental analysis, X-ray diffraction, surface roughness, specific
      surface area, density, and solubility. The ability of carbonated apatite to
      support mouse ES cell colonisation and maintenance in the presence of leukaemia
      inhibitory factor was determined by an enumeration of live versus dead cells
      within a population, and immunoreactivity to Oct4, a transcription factor and
      stem cell marker, following growth on each matrix. It was found that while both
      compositions allowed for the colonisation of mouse ES cells, the cells were not
      maintained in an undifferentiated state, as evidenced by a reduction in the
      number of cells staining positive for Oct4 expression. This study shows that an
      increase in carbonate content within sintered apatites leads to a higher cell
      number, a desired aspect for stem cells to populate scaffolds intended for tissue
      engineering. This study presents carbonated apatites as a suitable matrix for the
      initial colonisation and differentiation of ES cells for tissue engineering
      applications.

PMID- 16099499
TI  - Ca2+-dependent nuclear contraction in the heliozoon Actinophrys sol.
AB  - Ca2+-dependent contractility was found to exist in the nucleus of the heliozoon
      protozoan Actinophrys sol. Upon addition of Ca2+ ([Ca2+]free = 2.0 x 10(-3) M),
      diameters of isolated and detergent-extracted nuclei became reduced from 16.5+/
      1.7 microm to 11.0+/-1.3 microm. The threshold level of [Ca2+]free for the
      nuclear contraction was 2.9 x 10(-7) M. The nuclear contraction was not induced
      by Mg2+, and was not inhibited by colchicine or cytochalasin B. Contracted nuclei
      became expanded when Ca2+ was removed by EGTA; thus cycles of contraction and
      expansion could be repeated many times by alternating addition of Ca2+ and EGTA.
      The Ca2+-dependent nuclear contractility remained even after high salt treatment,
      suggesting a possible involvement of nucleoskeletal components in the nuclear
      contraction. Electron microscopy showed that, in the relaxed state, filamentous
      structures were observed to spread in the nucleus to form a network. After
      addition of Ca2+, they became aggregated and constructed a mass of thicker
      filaments, followed by re-distribution of the filaments spread around inside of
      the nucleus when Ca2+ was removed. These results suggest that the nuclear
      contraction is induced by Ca2+-dependent transformation of the filamentous
      structures in the nucleus.

PMID- 16099500
TI  - Calcium-dependent regulation of exocytosis.
AB  - A rapid increase in intracellular calcium directly triggers regulated exocytosis.
      In addition, changes in intracellular calcium concentration can adjust the extent
      of exocytosis (quantal content) or the magnitude of individual release events
      (quantal size) in both the short- and long-term. It is generally agreed that
      calcium achieves this regulation via an interaction with a number of different
      molecular targets located at or near to the site of membrane fusion. We review
      here the synaptic proteins with defined calcium-binding domains and protein
      kinases activated by calcium, summarize what is known about their function in
      membrane fusion and the experimental evidence in support of their involvement in
      synaptic plasticity.

PMID- 16099501
TI  - Ca2+ signalling in cardiogenesis.
AB  - A variety of InsP3-dependent Ca2+ signals coded in time, amplitude and space
      occur during the process of cardiac cell differentiation and heart development.
      Studies performed in both embryos and embryonic stem cell differentiating in
      cardiomyocytes have uncovered that Ca2+ regulates multiple steps of these
      biological processes in vertebrates. These include secretion of cardiogenic
      factors, cardiac transcriptional cascades and in turn gene expression,
      myofibrillogenesis and initiation of embryonic pacemaker activity. Evidence is
      accumulating to foresee Ca2+ as a major second messenger in directing the fate of
      stem cells and patterning the heart in the embryo.

PMID- 16099502
TI  - Effects of pO2 on the activation of skeletal muscle ryanodine receptors by NO: a
      cautionary note.
AB  - Eu et al., reported that O2 dynamically controls the redox state of 6-8 out of 50
      thiols per skeletal ryanodine receptor (RyR1) subunit and thereby tunes the
      response of Ca2+-release channels to authentic nitric oxide (NO) [J.P. Eu, J.
      Sun, L. Xu, J.S. Stamler, G. Meissner, The skeletal muscle calcium release
      channel: coupled O2 sensor and NO signaling functions, Cell 102 (2000) 499-509].
      A role for O2 was based on the observation that RyR1 can be activated by
      submicromolar NO at physiological ( approximately 10 mmHg) but not ambient
      (approximately 150 mmHg) pO2. At ambient pO2, these critical thiols were oxidized
      but incubation at low pO2 reset the redox state of these thiols, closed RyR1
      channels and made these thiols available for nitrosation by low NO
      concentrations. Eu et al., postulated the existence of a redox/O2sensor that
      couples channel activity to NO and pO2 and explained that "the nature of the
      'redox/O2 sensor' that couples channel activity to intracellular redox chemistry
      is a mystery". Here, we re-examined the effect of pO2 on RyR1 and find that
      incubation of RyR1 at low pO2 did not alter channel activity and NO (0.5-50
      microM) failed to activate RyR1 despite a wide range of pO2 pre-incubation
      conditions. We show that low levels of NO do not activate RyR1, do not reverse
      the inhibition of RyR1 by calmodulin (CaM) even at physiological pO2. Similarly,
      the pre-incubation of SR vesicles in low pO2 (for 10-80 min) did not inhibit
      channel activity or sensitization of RyR1 to NO. We discuss the significance of
      these findings and propose that caution should be taken when considering a role
      for pO2 and nitrosation by NO as mechanisms that tune RyRs in striated muscles.

PMID- 16099503
TI  - The dynamics of stochastic attrition viewed as an absorption time on a
      terminating Markov chain.
AB  - Localized Ca(2+) elevations known as Ca(2+) puffs and sparks are cellular signals
      that arise from the cooperative activity of clusters of inositol 1,4,5
      trisphosphate receptors and ryanodine receptors clustered at Ca(2+) release sites
      on the surface of the endoplasmic reticulum or sarcoplasmic reticulum. When
      Markov chain models of these intracellular Ca(2+)-regulated Ca(2+) channels are
      coupled via a mathematical representation of Ca(2+) microdomain, simulated Ca(2+)
      release sites may exhibit the phenomenon of "stochastic Ca(2+) excitability"
      where the inositol 1,4,5-trisphosphate receptors (IP(3)Rs) or ryanodine receptors
      (RyRs) open and close in a concerted fashion. Interestingly, under some
      conditions simulated puffs and sparks can be observed even when the single
      channel model used does not include slow Ca(2+) inactivation or, indeed, any long
      lived closed/refractory state [V. Nguyen, R. Mathias, G. Smith, Stochastic
      automata network descriptor for Markov chain models of instantaneously-coupled
      intracellular Ca(2+) channels, Bull. Math. Biol. 67 (2005) 393-432]. In this
      case, termination of the localized Ca(2+) elevation occurs when all of the
      intracellular channels at a release site simultaneously close through a process
      referred to as stochastic attrition [M. Stern, Theory of excitation-contraction
      coupling in cardiac muscle, Biophys. J. 63 (1992) 497-517]. In this paper, we
      investigate the statistical properties of stochastic attrition viewed as an
      absorption time on a terminating Markov chain that represents a Ca(2+) release
      site composed of N two-state channels that are activated by Ca(2+). Assuming that
      the local [Ca(2+)] experienced by a channel depends only on the number of open
      channels at the Ca(2+) release site (i.e., instantaneous mean-field coupling
      [ibid.], we derive the probability distribution function for the time until
      stochastic attrition occurs and present an analytical formula for the expectation
      of this random variable. We explore how the contribution of stochastic attrition
      to the termination of Ca(2+) puffs and sparks depends on the number of channels
      at a release site, the source amplitude of the channels (i.e., the strength of
      the coupling), the background [Ca(2+)], channel kinetics, and the cooperactivity
      of Ca(2+) binding. Because we explicitly model the Ca(2+) regulation of the
      intracellular channels, our results differ markedly from (and in fact generalize)
      preliminary analyses that assume the intracellular Ca(2+) channels are uncoupled
      and consequently independent.

PMID- 16099504
TI  - Cellular calcium mobilization in response to phosphoinositide delivery.
AB  - Intracellular calcium [Ca(2+)](i) is mobilized in many cell types in response to
      activation of phosphoinositide (PIP(n)) signaling pathways involving
      PtdIns(4,5)P(2) or PtdIns(3,4,5)P(3). To further explore the relationship between
      increases in intracellular PIP(n) concentrations and mobilization of [Ca(2+)](i),
      each of the seven phosphorylated phosphoinositides (PIP(n)s) were delivered into
      cells and the metabolism and physiological effects of the exogenously
      administered PIP(n)s were determined. The efficient cellular delivery of
      fluorophore-tagged and native PIP(n)s was accomplished using histone protein,
      neomycin, and dendrimeric polyamines. PtdIns(4,5)P(2) fluorophore-tagged analogs
      with short- and long-acyl chains were substrates for cellular enzymes in vitro
      and for phospholipases in stimulated fibroblasts. PtdIns(4)P, PtdIns(3,4)P(2) and
      PtdIns(4,5)P(2), each induced calcium mobilization rapidly after exogenous
      addition to fibroblasts. PtdIns(3,4,5)P(3) induced a significant, but smaller
      increase in intracellular calcium. These observations suggest that PIP(n)s other
      than PtdIns(4,5)P(2) or PtdIns(3,4,5)P(3) may have direct roles in signaling
      involving [Ca(2+)](i).

PMID- 16099505
TI  - Angiogenesis in relation to clinical stage, apoptosis and prognostic score in
      myelodysplastic syndromes.
AB  - The International Prognostic Scoring System (IPSS), based on the number of
      cytopenias, percentage of bone marrow blasts and cytogenetics, is an important
      prognostic tool for patients with myelodysplastic syndrome (MDS). In addition,
      factors such as high bone marrow cellularity and lactate dehydrogenase levels
      have been associated with an adverse outcome, spontaneously and after
      chemotherapy. Recently, increased bone marrow angiogenesis, measured as, e.g.
      microvascular density (MVD), was reported to be more intense in high-risk than in
      low-risk MDS. To assess the prognostic role of MVD in MDS, a cohort of 56
      patients, thoroughly investigated for various clinical and morphological
      parameters, were followed-up for survival > or =60 months after the diagnostic
      analysis. As a group MDS patients had higher MVD compared to healthy controls
      (p<0.02). The highest median MVD value was observed in the RAEB group, but there
      was no overall significant difference between the FAB groups. No significant
      correlations were observed between MVD and peripheral blood counts, bone marrow
      cellularity, percentage of bone marrow blasts and CD34 positive cells, apoptotic
      index (TUNEL), proliferation index (MIB-1), erythroid index, FAB group and IPSS
      score. MVD was not correlated to overall survival. In contrast, bone marrow blast
      count <5%, low or normal cellularity, as well as a high erythroid index,
      indicated a favorable survival. Thus, our data do not support an important
      prognostic role of angiogenesis, reflected by microvessel density, in the
      myelodysplastic syndromes.

PMID- 16099506
TI  - Effects of clomazone herbicide on hematological and some parameters of protein
      and carbohydrate metabolism of silver catfish Rhamdia quelen.
AB  - The effects of clomazone (0.5 and 1.0 mg/L) according to nominal concentrations
      used in paddy rice fields (0.4-0.7 mg/L) on protein and carbohydrate metabolism
      and haematological parameters were evaluated in silver catfish (Rhamdia quelen)
      after 12, 24, 48, 96 and 192 h of exposure with a recovery period of 96 and 192
      h. Liver glycogen increased significantly (P<0.05) in all periods and
      concentrations tested. The maximum glycogen increase reaches 250% after 12h of
      exposure. Muscle glycogen reduced significantly after 24, 48, 96 and 192 h for
      both clomazone concentrations (P<0.05). Significantly elevated plasma glucose
      values (P<0.05) and variation in glucose in the liver and muscle of exposed fish
      were observed. Muscle lactate levels increased after 12, 24 and 48 h of clomazone
      exposure (22-67%), but reduced in the liver (P<0.05). Protein levels were
      enhanced in the liver and white muscle, except at 96 and 192 h of exposure,
      whereas it increased in the plasma in the period from 48 to 96 h (P<0.05).
      Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities
      were significantly elevated in the plasma (P<0.05). In the liver, ALT increased
      after 24 h, while AST activity was enhanced only after 12 h of exposure.
      Hematocrit contents were reduced after 96 and 192 h of exposure. Most of the
      metabolic disorders observed did not persist after the recovery period, except
      for the liver AST and ALT activity. Clomazone concentrations used in this study
      appear safe to fish, Rhamdia quelen, because overall parameters can be recovered
      after 96 and 192 h in clean water. ALT and AST activity may be an early biomarker
      of clomazone toxicity.

PMID- 16099507
TI  - Mechanisms underlying epigenetic effects of early social experience: the role of
      neuropeptides and steroids.
AB  - In mammals the neonatal period is a time of significant social interaction. This
      is true even in solitary species as females spend a significant amount of time
      nursing and caring for their offspring. In social species interactions may also
      include the father, older siblings and extended family members. This period is a
      time of significant development, including organization of the central nervous
      system, and therefore a time when the degree and type of social interaction
      influences the development and expression of social behavior in adulthood. The
      purpose of this review is to examine the possible mechanisms for the epigenetic
      effects of early social experience on the subsequent expression of social
      behavior. We propose that social interactions during the neonatal period organize
      the subsequent expression of behavior by altering sensitivity to neuropeptides
      and steroids. Both neuropeptides (e.g. oxytocin and arginine vasopressin) and
      steroids (e.g. estrogen) regulate or influence the expression of behaviors such
      as affiliation, aggression, sociosexual behavior, parental behavior, and
      responses to stress. Therefore, changes in sensitivity to these hormones via
      reorganization of receptors or changes in hormone production and secretion are
      potentially powerful mechanisms through which early social experience can mold
      subsequent social behaviors.

PMID- 16099508
TI  - The neurobiology of positive emotions.
AB  - Compared to the study of negative emotions such as fear, the neurobiology of
      positive emotional processes and the associated positive affect (PA) states has
      only recently received scientific attention. Biological theories conceptualize PA
      as being related to (i) signals indicating that bodies are returning to
      equilibrium among those studying homeostasis, (ii) utility estimation among those
      favoring neuroeconomic views, and (iii) approach and other instinctual behaviors
      among those cultivating neuroethological perspectives. Indeed, there are probably
      several distinct forms of positive affect, but all are closely related to ancient
      sub-neocortical limbic brain regions we share with other mammals. There is now a
      convergence of evidence to suggest that various regions of the limbic system,
      including especially ventral striatal dopamine systems are implemented in an
      anticipatory (appetitive) positive affective state. Dopamine independent
      mechanisms utilizing opiate and GABA receptors in the ventral striatum, amygdala
      and orbital frontal cortex are important in elaborating consummatory PA (i.e.
      sensory pleasure) states, and various neuropeptides mediate homeostatic
      satisfactions.

PMID- 16099509
TI  - Modulating apoptosis as a target for effective therapy.
AB  - Alterations in cell proliferation and cell death are essential determinants in
      the pathogenesis and progression of several diseases such as cancer,
      neurodegenerative disorders or autoimmune diseases among others. Complex networks
      of regulatory factors determine whether cells proliferate or die. Recent progress
      in understanding the molecular changes offer the possibility of specifically
      targeting molecules and pathways to achieve more effective and rational
      therapies. Drugs that target molecules involved in apoptosis are used as
      treatment against several diseases. Candidates such as TNF death receptor family,
      caspase inhibitors, antagonists of the p53-MDM2 interaction, NF-kappaB and PI3K
      pathways and Bcl-2 family members have been targeted as cancer cell killing
      agents. Moreover, apoptosis of tumor cells can also be achieved by targeting the
      inhibitor of apoptosis proteins, IAPs, in addition to the classical
      antiproliferative approach. Disruption of STAT activation and interferon beta
      therapy have been used as a treatment to prevent the progression of some
      autoimmune diseases. In models of Parkinson's, Alzheimer's and amyotrophic
      lateral sclerosis, blocking of Par-4 expression or function, as well as caspase
      activation, prevents neuronal cell death. Finally, it has been shown that gene
      therapy may be an encouraging approach for treatment of neurodegenerative
      disorders.

PMID- 16099510
TI  - Deletion analysis of the rodent selenoprotein W promoter.
AB  - To identify regulatory elements in the rat selenoprotein W (SeW) promoter, 2090,
      1265, 741, and 404 base pair truncations of genomic DNA lying immediately
      upstream of the SeW coding sequence were cloned into a luciferase reporter vector
      (pGL3-Basic from Promega, Madison, WI, USA). 3656 and 406 base pair mouse SeW
      promoter constructs were also compared. SeW promoter activity was assayed in two
      rat cell lines: L8 muscle cells and C6 brain cells. The SeW promoter was 2-7
      times more active (p<0.01) than SV40 promoter. Promoter activity of constructs of
      the SeW promoter ranging from 200 base pairs to 51 base pairs gradually decreased
      to zero in brain cells, but fell precipitously to zero in muscle cells. Some
      truncations stimulated promoter activity, suggesting the full-length promoter may
      contain binding sites for factors that suppress SeW expression.

PMID- 16099511
TI  - Bis(3-hydroxy-4-pyridinone)-EDTA derivative as a potential therapeutic Al
      chelating agent. Synthesis, solution studies and biological assays.
AB  - The 3-hydroxy-4-pyridinones are chelating agents of current interest due to their
      high affinity for hard metal ions and potential clinical applications as metal
      decorporation agents. A new bis-(3-hydroxy-4-pyridinone) derivative of EDTA have
      been developed, and herein we describe the results of solution studies to
      determine the protonation constants and the partition coefficient.
      Biodistribution studies, performed with 67Ga-overload mice, showed rapid
      clearance of the radiotracer from the body, thus indicating that the new ligand
      should be a quite effective agent for the in vivo aluminium removal.

PMID- 16099512
TI  - Frequency decomposition of conditional Granger causality and application to
      multivariate neural field potential data.
AB  - It is often useful in multivariate time series analysis to determine statistical
      causal relations between different time series. Granger causality is a
      fundamental measure for this purpose. Yet the traditional pairwise approach to
      Granger causality analysis may not clearly distinguish between direct causal
      influences from one time series to another and indirect ones acting through a
      third time series. In order to differentiate direct from indirect Granger
      causality, a conditional Granger causality measure in the frequency domain is
      derived based on a partition matrix technique. Simulations and an application to
      neural field potential time series are demonstrated to validate the method.

PMID- 16099513
TI  - Superiority of nonlinear mapping in decoding multiple single-unit neuronal spike
      trains: a simulation study.
AB  - One of the most important building blocks of the brain-machine interface (BMI)
      based on neuronal spike trains is the decoding algorithm, a computational method
      for the reconstruction of desired information from spike trains. Previous studies
      have reported that a simple linear filter is effective for this purpose and that
      no noteworthy gain is achieved from the use of nonlinear algorithms. In order to
      test this premise, we designed several decoding algorithms based on the linear
      filter, and two nonlinear mapping algorithms using multilayer perceptron (MLP)
      and support vector machine regression (SVR). Their performances were assessed
      using multiple neuronal spike trains generated by a biophysical neuron model and
      by a directional tuning model of the primary motor cortex. The performances of
      the nonlinear algorithms, in general, were superior. The advantages of using
      nonlinear algorithms were more profound for cases where false-positive/negative
      errors occurred in spike trains. When the MLPs were trained using trial-and
      error, they often showed disappointing performance comparable to that of the
      linear filter. The nonlinear SVR showed the highest performance, and this may be
      due to the superiority of SVR in training and generalization.

PMID- 16099514
TI  - Live-cell imaging methods for the study of vagal afferents within the nucleus of
      the solitary tract.
AB  - Substantial evidence suggests that vagal afferent functions are modulated by
      agonists acting on afferent terminals in the solitary nucleus (NST). Actions of
      these agonists are implied through intracellular recordings from cultured nodose
      ganglion cells or second order NST neurons. While high-quality data have been
      obtained using these methods, techniques in which physiological measurements can
      be made directly on the afferent terminal fields, in situ, in the NST, would
      eliminate several potential interpretive problems inherent in these less direct
      approaches. This paper describes methods developed to directly measure changes in
      presynaptic cytoplasmic calcium in vagal afferents using time-lapse laser
      confocal microscopy on the in vitro brainstem slice. Calcium green dextran (CG)
      transported from the nodose ganglion clearly demonstrates vagal afferent fibers
      ramifying throughout the NST in the in vitro brainstem slice. CG-labeled vagal
      afferents can be repeatedly activated by focal electrical stimulation, by
      agonists acting on presynaptic ligand-gated ion channels, and by molecules that
      are presumed to act directly on vagal afferents based on previous physiological
      and immunocytochemical studies. Image and preparation stability are a challenge
      to the success of the experiment; however, methods described here should assist
      direct studies of transduction events within other afferent terminal fields in
      the CNS.

PMID- 16099515
TI  - Differential expression of inducible nitric oxide synthase and cytokine mRNA in
      chicken lines divergent for cutaneous hypersensitivity response.
AB  - Phytohemagglutinin (PHA)-induced delayed-type hypersensitivity is an
      immunocompetent trait considered an indicator of cell-mediated immune or T-cell
      responses. Divergent selection was performed to generate high and low lines for
      response to PHA-P. Extreme-responder birds of the F2 generation in each line were
      used to study possible differences in macrophage activity and the associated
      functional genes. To evaluate macrophage activity, nitric oxide (NO) was
      estimated both systemically in serum and in in vitro monocyte culture. Semi
      quantitative RT-PCR was used to detect the differential mRNA expression patterns
      of iNOS and MIP-1beta in monocyte culture, whereas T(H)1 cytokines (IL-2 and IFN
      gamma) were studied in peripheral blood mononuclear cells (PBMC) at different
      time intervals after lipopolysaccharide (LPS) induction. The high line showed
      strong systemic, as well as in vitro NO production, compared to the low line,
      upon stimulation with NDV and LPS, similar to early and high iNOS mRNA
      expression. Following the pattern of iNOS gene expression, an early strong
      expression of cytokines with powerful iNOS-inducing action, such as IFN-gamma and
      the chemokine MIP-1beta, was observed in the high line. In contrast, for response
      to PHA-P, low expression of IL-2 was observed in the high compared to the low
      line. In conclusion, the study revealed that divergent selection for response to
      PHA-P resulted in a divergent effect on T(H)1 cell activity, resulting in altered
      macrophage function in chickens. Selection, based on response to PHA-P, could
      lead to more resistant birds or birds with an enhanced immune response.

PMID- 16099516
TI  - A store-operated Ca2+ influx activated in response to the depletion of
      thapsigargin-sensitive Ca2+ stores is developmentally regulated in embryonic
      cortical neurons from mice.
AB  - Store-operated channels (SOCs) are recruited in response to the release of Ca2+
      from intracellular stores. They allow a voltage-independent entry of Ca2+ into
      the cytoplasm also termed capacitative Ca2+ entry (CCE). In neurons, the
      functional significance of this Ca2+ route remains elusive. Several reports
      indicate that SOCs could be developmentally regulated. We verified the presence
      of a CCE in freshly dissociated cortical cells from E13, E14, E16, E18 fetuses
      and from 1-day-old mice. Intracellular Ca2+ stores were depleted by means of the
      SERCA pump inhibitor thapsigargin. At E13, the release of Ca2+ from thapsigargin
      sensitive compartments gave rise to an entry of Ca2+ in a minority of cells. This
      Ca2+ route, insensitive to voltage-gated Ca2+ channel antagonists like Cd2+ and
      Ni2+, was blocked by the SOC inhibitor SKF-96365. After E13 and on E13 cells kept
      in culture, there is a marked increase in the percentage of cells with functional
      SOCs. The lanthanide La3+ fully inhibited the CCE from neonatal mice whereas it
      weakly blocked the thapsigargin-dependent Ca2+ entry at E13. This suggests that
      the subunit composition of the cortical SOCs is developmentally regulated with
      La3+-insensitive channels being expressed in the embryonic cortex whereas La3+
      sensitive SOCs are found at birth. Our data argue for the presence of SOCs in
      embryonic cortical neurons. Their expression and pharmacological properties are
      developmentally regulated.

PMID- 16099517
TI  - Identification of a very large Rab GTPase family in the parasitic protozoan
      Trichomonas vaginalis.
AB  - Rab proteins are pivotal components of the membrane trafficking machinery in all
      eukaryotes. Distinct Rab proteins locate to specific endomembrane compartments
      and genomic studies suggest that Rab gene diversity correlates with endomembrane
      system complexity; for example unicellular organisms generally possess 5-20 Rab
      family members and the size of the repertoire increases to 25-60 in multicellular
      systems. Here we report 65 open reading frames from the unicellular protozoan
      Trichomonas vaginalis that encode distinct Rab proteins (TvRabs), indicating a
      family with complexity that rivals Homo sapiens in number. The detection of gene
      transcripts for the majority of these genes and conservation of functional motifs
      strongly suggests that TvRabs retain functionality and likely roles in membrane
      trafficking. The T. vaginalis Rab family includes orthologues of the conserved
      subfamilies, Rab1, Rab5, Rab6, Rab7 and Rab11, but the majority of TvRabs are not
      represented by orthologues in other systems and includes six novel T. vaginalis
      specific Rab subfamilies (A-F). The extreme size of the T. vaginalis Rab family,
      the presence of novel subfamilies plus the divergent nature of many TvRab
      sequences suggest both the presence of a highly complex endomembrane system
      within Trichomonas and potentially novel Rab functionality. A family of more than
      65 Rab genes in a unicellular genome is unexpected, but may be a requirement for
      progression though an amoeboid life-cycle phase as both Dictyostelium discoideum
      and Entamoeba histolytica share with T. vaginalis both an amoeboid life cycle
      stage and very large Rab gene families.

PMID- 16099518
TI  - Beneficial effects of high doses of growth hormone in the introduction and
      optimization of medical treatment in decompensated congestive heart failure.
AB  - BACKGROUND: Optimizing oral therapy in patients with unstable decompensated
      and/or dobutamine-dependent congestive heart failure (CHF) is a challenge.
      METHODS AND RESULTS: We investigated the effects of high doses of recombinant
      human growth hormone (GH) in 6 patients with cardiac cachexia and unstable
      decompensated CHF (5 dobutamine-dependent), including its influence in the
      optimization of oral CHF treatment. Patients received 8 IU of subcutaneous GH per
      day for median 26 (range 61) days. GH improved the systolic systemic blood
      pressure (SSBP, in mm Hg) from median 85 (range 34) to 100 (20) (p<.01), and the
      left ventricular (LV) ejection fraction (in %) from median 23 (range 22)
      (pretreatment) to 28 (18) (posttreatment) and 38 (28) (later) (p<.007). The NYHA
      functional class improved from IV to I in 2 patients, from IV to II in 3, and
      from IV to II-III in one. All patients were discharged from the hospital. It was
      possible in the hospital to initiate and after discharge to optimize long-term
      CHF treatment from 37.5 to 50 mg of carvedilol in 5 patients and with higher
      doses of captopril (from 50 to 150 mg) in all patients. Three patients are alive
      after 67, 75, and 11 months of follow-up. The remaining 3 patients died from a
      pulmonary abscess at 9 months, septicemia at 21 months, and progressive heart
      failure due to unplanned withdrawal of carvedilol at 36 months. CONCLUSION: The
      use of GH in patients with decompensated CHF and cardiac cachexia provided
      clinical stability without the need for inotropic drugs permitting introduction
      of nonpreviously tolerated drugs. This could represent a new option for
      optimizing long-term CHF therapy and discharging hospitalized patients who are
      dobutamine-dependent.

PMID- 16099519
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy. A review and update.
AB  - The arrhythmogenic right ventricular dysplasia/cardiomyopathy is an important
      cause of sudden arrhythmic death, often exertional, in young individuals and
      athletes. Although the aetiology remains partially unknown, genetic abnormalities
      have been demonstrated. Reported prevalence is 1 in 5000 individuals but it is
      considered there are many non-diagnosed cases. The characteristic pathologic
      finding is the progressive fibro-fatty replacement of the right ventricular
      myocardium. The clinical manifestations vary from asymptomatic patients with an
      episode of sudden cardiac death as first symptom to chronically symptomatic
      patients with recurrent palpitations and/or right or biventricular failure.
      Approximately a third of the patients show the characteristic Epsilon wave in the
      12-lead ECG which is a useful screening test. Signal-averaged ECG frequently
      demonstrates late potentials. The two-dimensional echocardiography, magnetic
      resonance imaging, computerized tomography and right ventricular cineangiography
      show morphologic abnormalities in the right ventricle. Therapy is directed to
      prevent and/or treat malignant ventricular tachyarrhythmias with medications,
      implantable cardioverter defibrillator and radiofrequency ablation in selected
      cases.

PMID- 16099520
TI  - An assessment of the efficiency of fungal DNA extraction methods for maximizing
      the detection of medically important fungi using PCR.
AB  - To date, no single reported DNA extraction method is suitable for the efficient
      extraction of DNA from all fungal species. The efficiency of extraction is of
      particular importance in PCR-based medical diagnostic applications where the
      quantity of fungus in a tissue biopsy may be limited. We subjected 16 medically
      relevant fungi to physical, chemical and enzymatic cell wall disruption methods
      which constitutes the first step in extracting DNA. Examination by light
      microscopy showed that grinding with mortar and pestle was the most efficient
      means of disrupting the rigid fungal cell walls of hyphae and conidia. We then
      trialled several published DNA isolation protocols to ascertain the most
      efficient method of extraction. Optimal extraction was achieved by incorporating
      a lyticase and proteinase K enzymatic digestion step and adapting a DNA
      extraction procedure from a commercial kit (MO BIO) to generate high yields of
      high quality DNA from all 16 species. DNA quality was confirmed by the successful
      PCR amplification of the conserved region of the fungal 18S small-subunit rRNA
      multicopy gene.

PMID- 16099521
TI  - An inter-centre quality assurance network for IMRT verification: results of the
      ESTRO QUASIMODO project.
AB  - BACKGROUND AND PURPOSE: IMRT necessitates extension of existing inter-centre
      quality assurance programs due to its increased complexity. We assessed the
      feasibility of an inter-centre verification method for different IMRT techniques.
      MATERIALS AND METHODS: Eight European radiotherapy institutions of the QUASIMODO
      network, have designed an IMRT plan for a horseshoe-shaped PTV surrounding a
      cylindrical OAR in a simplified pelvic phantom. All centres applied common plan
      objectives but used their own equipment for planning and delivery. They verified
      the delivery of this plan according to a common protocol with radiographic film
      and ionisation chamber measurements. The irradiated films, the results of the
      ionisation chamber measurements and the computed dose distributions were sent to
      one analysis centre that compared the measured and computed dose distributions
      with the gamma method and composite dose-area histograms. RESULTS: 4% (relative
      to the prescribed dose) and 3mm (distance-to-agreement) were decided feasible
      gamma criteria. The composite dose-area histograms showed a maximum local
      deviation of 3.5% in the mean dose of the PTV and 5% in the OAR. Systematic
      differences could be identified, and in some cases explained. CONCLUSIONS: This
      multi-centre dosimetric verification study demonstrated both the feasibility of a
      multi-centre quality assurance network to evaluate any IMRT planning and delivery
      system combination, as well as the validity of the methodology involved.

PMID- 16099522
TI  - Modelling relative motion to facilitate intra-limb coordination.
AB  - The importance of relative motion information when modelling a novel motor skill
      was examined. Participants were assigned to one of four groups. Groups 1 and 2
      viewed demonstrations of a skilled cricket bowler presented in either 'video' or
      'point light' format. Group 3 observed a single point of light pertaining to the
      'wrist' of the skilled bowler only. Participants in Group 4 did not receive a
      demonstration and acted as controls. During 60 acquisition trials, participants
      in the demonstration groups viewed a model five times before each 10-trial block.
      Retention was examined the following day. Intra-limb coordination was assessed
      for the right elbow relative to the wrist in comparison to the model. The
      demonstration groups showed greater concordance with the model than the control
      group. However, the 'wrist' group performed less like the model than the 'point
      light' and 'video' groups, who did not differ from each other. These effects were
      maintained in retention. Relative motion information aided the acquisition of
      intra-limb coordination, while making this information more salient (through
      point lights) provided no additional benefit. The motion of the model's bowling
      arm was replicated more closely than the non-bowling arm, suggesting that
      information from the end-effector is prioritized during observation for later
      reproduction.

PMID- 16099523
TI  - Inactivation of Salmonella typhimurium DT 104 in UHT whole milk by high
      hydrostatic pressure.
AB  - Cell suspensions of Salmonella typhimurium DT 104 in ultra-high temperature (UHT)
      whole milk were exposed to high hydrostatic pressure at 350, 400, 450, 500, 550,
      and 600 MPa at ambient temperature (ca. 21 degrees C). Tailing was observed in
      all survival curves, and sigmoidal survival curves were observed at relatively
      high pressure (500-600 MPa). Four modeling methods (linear and nonlinear
      including Weibull, modified Gompertz, and log-logistic models) were fitted to
      these data at 500, 550, and 600 MPa. Performances of the modeling methods were
      compared using mean square error (MSE). The linear regression model at these
      three pressure levels had a mean square error (MSE) of 1.260-2.263. Nonlinear
      regressions using Weibull, modified Gompertz, and log-logistic models had MSE
      values in the range of 0.334-0.764, 0.601-1.479, and 0.359-0.523, respectively.
      Modeling results indicated that first-order kinetics could not accurately
      describe pressure inactivation of S. typhimurium DT 104 in UHT milk; the log
      logistic model produced the best fit to data.

PMID- 16099524
TI  - Isolation and characterisation of a Lactobacillus helveticus ITG LH1 peptidase
      rich sub-proteome.
AB  - Lactobacillus helveticus strains, one of the most nutritionally fastidious lactic
      acid bacteria, have a potent proteolytic system that makes them very interesting
      for different uses in the dairy industry. Its applications concern from cheese
      ripening to the preparation of fermented milk products with biologically active
      peptides. The cell-free extract (CFE) of Lactobacillus helveticus strain ITG LH1
      was analysed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE),
      using IPG immobiline dry strips (pH 4-7). With the aim to study the proteolytic
      enzymes expressed by Lactobacillus helveticus ITG LH1 grown in milk medium, a two
      step-chromatography methodology, based on ion exchange and affinity
      chromatography, was developed for the preparation of a peptidase-rich sub
      proteome from the CFE of stationary growing cells. Several affinity
      chromatography columns were tested and among them a HiTrap Chelating column was
      selected as it provided the best performance for the enrichment in peptidases.
      Peptidase activities were studied using different beta-Naphtylamide (beta-NA)
      derivatives and specific activities were increased 50- to 100-fold by this
      chromatographic procedure. Sub-proteome characterisation was performed by 2D
      PAGE, pH 4-7, followed by protein digestion with trypsin, analysis by MALDI-TOF
      mass spectrometry and subsequent database searches using peptide mass
      fingerprints. Among the most abundant proteins seven peptidases were present,
      namely the two general aminopeptidases (PepN, PepC), three dipeptidases (PepDA,
      PepV, PepQ) and two endopeptidases (PepO, PepO3), all of them corresponding to
      the catalytic classes of metallo- or cysteine-peptidases. Several stress proteins
      (such as heat shock proteins DnaK and GroEL) and other enzymes implied in
      bacterial metabolism, namely in the carbohydrate pathways (such as LDH), were
      also identified in the peptidase-rich sub-proteome.

PMID- 16099525
TI  - Effect of porosity on the release kinetics of propafenone-loaded PEG-g-PLA
      nanoparticles.
AB  - Nanoparticle preparation by the emulsification-solvent evaporation method is a
      complex phenomenon. Various formulation factors can affect the internal structure
      and release of drug from nanoparticles (NPs). The aim of the present study is to
      optimize NPs of PEG-g-PLA polymer and study the effect of various factors on the
      porosity as well as release profile of drug-loaded NPs. Propafenone hydrochloride
      (Prop.HCl), a model drug, was encapsulated in NPs using different amounts of
      triethylamine (TEA) and initial drug loading levels. NPs were also prepared
      without TEA by using propafenone base (Prop). All the formulations were
      characterized for surface morphology, size and size distribution, encapsulation
      efficiency, thermal analysis, porosimetry and in vitro release studies.
      Encapsulation efficiency of Prop ranged between 10% and 43% and was dependent on
      initial drug loading as well as amount of TEA added. Porosity studies revealed
      different pore size distribution (PSD) for formulations with and without TEA.
      Formulations with higher drug loading showed greater volume contribution of small
      pores, higher fractal dimension suggesting more complex pore structure and slower
      drug release, probably due to decrease in the effective diffusion coefficient of
      Prop. Results suggest that formulation factors play an important role affecting
      the porosity and release rate of NPs. Also, fractal dimension could be one of the
      most important factors in determining the release behavior of NPs.

PMID- 16099526
TI  - Three patients with middle-age-onset hemochromatosis caused by novel mutations in
      the hemojuvelin gene.
AB  - Hemochromatosis is a genetically heterogeneous condition. Mutations in the
      recently described hemojuvelin gene were found in patients with juvenile
      hemochromatosis, who usually manifest clinical signs of iron overload, including
      cardiomyopathy and hypogonadism, in their teens and early 20s. In this report, we
      describe three Japanese patients who showed typical clinical and hepatic
      histological damage compatible with hemochromatosis at around 50 years of age.
      Genetic analyses showed that all three patients carried mutations in the
      hemojuvelin gene. The first patient was homozygous for a novel mutation (745G > C
      [D249H]), and the second and third patients from the same family were homozygous
      for another novel mutation (934C > T [Q312X]). No mutations in their HFE,
      hepcidin, transferrin receptor 2, or ferroportin genes were found. One patient
      had chronic infection with Helicobacter pylori. The age at initial presentation
      of hemojuvelin-hemochromatosis occurs over a wider range than previously
      described.

PMID- 16099527
TI  - HCV natural history: the retrospective and prospective in perspective.

PMID- 16099528
TI  - Mutagenic effects of ribavirin in vivo.

PMID- 16099529
TI  - Diagnosis and management of tuberculosis by private practitioners in Manila,
      Philippines.
AB  - SETTING: Private for-profit health care providers are prominent in the health
      system of the Philippines. OBJECTIVES: To examine the practices of the private
      practitioners in Malabon, Metropolitan Manila, Philippines, concerning diagnosis
      and treatment of tuberculosis (TB). DESIGN: Forty-five private practitioners of
      Malabon who treat adult TB patients were interviewed. RESULTS: For diagnosis,
      most private practitioners relied on the clinical presentation and result of an X
      ray. Only 13% of the respondents routinely also asked for sputum examination.
      Ninety-six percent used X-ray as a tool to monitor treatment. Sixty percent of
      the respondents prescribed a regimen consisting of isoniazid, rifampicin,
      pyrazinamide, and ethambutol. Except for rifampicin, over-dosage was common. For
      re-treatment cases, none prescribed the WHO-recommended re-treatment regimen. The
      private practitioners perceived the main reasons for patient non-adherence to be
      the patients' lack of finances to buy drugs and patients' perceived well being
      after a certain period of treatment. Patients' lack of money was seen as the main
      obstacle to compliance. The only case holding mechanism mentioned was occasional
      clinic appointments of the TB patients. CONCLUSION: Private practices for
      diagnosis and treatment of TB typically deviate from guidelines. The quality of
      care among private practitioners needs improvement. Innovative strategies are
      required.

PMID- 16099530
TI  - The Norwegian hospital reform of 2002: central government takes over ownership of
      public hospitals.
AB  - Starting in January 2002, the majority of the Norwegian Parliament transferred
      the ownership of all public hospitals from the county governments to the central
      state. This round of reforms represents the most recent attempt by the central
      government to resolve major problems in the Norwegian health care system. In this
      paper, we describe these reforms and the problems they are intended to remedy. We
      also indicate further proposals that we believe need to be accomplished to ensure
      that the reforms become successful. The main lesson to be learned from the
      Norwegian experiment is that central government involvement in local and county
      government decision-making can lead to ambiguous responsibilities and a lack of
      transparency. This appears to be particularly the case when central government
      involvement implies shared responsibilities for the financing of particular
      services.

PMID- 16099531
TI  - Is there any sense in antisense editing?
AB  - Several recent studies have hypothesized that sense-antisense RNA-transcript
      pairs create dsRNA duplexes that undergo extensive A-to-I RNA editing. We studied
      human and mouse genomic antisense regions and found that the editing level in
      these areas is negligible. This observation questions the scope of sense
      antisense duplexes formation in-vivo, which is the basis for several proposed
      regulatory mechanisms.

PMID- 16099532
TI  - Comparative genomics of nematodes.
AB  - Recent transcriptome and genome projects have dramatically expanded the
      biological data available across the phylum Nematoda. Here we summarize analyses
      of these sequences, which have revealed multiple unexpected results. Despite a
      uniform body plan, nematodes are more diverse at the molecular level than was
      previously recognized, with many species- and group-specific novel genes. In the
      genus Caenorhabditis, changes in chromosome arrangement, particularly local
      inversions, are also rapid, with breakpoints occurring at 50-fold the rate in
      vertebrates. Tylenchid plant parasitic nematode genomes contain several genes
      closely related to genes in bacteria, implicating horizontal gene transfer events
      in the origins of plant parasitism. Functional genomics techniques are also
      moving from Caenorhabditis elegans to application throughout the phylum. Soon,
      eight more draft nematode genome sequences will be available. This unique
      resource will underpin both molecular understanding of these most abundant
      metazoan organisms and aid in the examination of the dynamics of genome evolution
      in animals.

PMID- 16099533
TI  - Characterization of EEG--a comparative study.
AB  - The Electroencephalogram (EEG) is a representative signal containing information
      about the condition of the brain. The shape of the wave may contain useful
      information about the state of the brain. However, the human observer cannot
      directly monitor these subtle details. Besides, since bio-signals are highly
      subjective, the symptoms may appear at random in the time scale. Therefore, the
      EEG signal parameters, extracted and analyzed using computers, are highly useful
      in diagnostics. Chaotic measures like correlation dimension (CD), largest
      Lyapunov exponent (LLE), Hurst exponent (H) and entropy are used to characterize
      the signal. Results indicate that these nonlinear measures are good
      discriminators of normal and epileptic EEG signals. These measures distinguish
      epileptic EEG and alcoholic from normal EEG with an accuracy of more than 90%.
      The dynamical behavior is less random for alcoholic and epileptic compared to
      normal. This indicates less of information processing in the brain due to the
      hyper-synchronization of the EEG. Hence, the application of nonlinear time series
      analysis to EEG signals offers insight into the dynamical nature and variability
      of the brain signals. As a pre-analysis step, the EEG data is tested for
      nonlinearity using surrogate data analysis and the results exhibited a
      significant difference in the correlation dimension measure of the actual data
      and the surrogate data.

PMID- 16099534
TI  - The impact of additives found in industrial formulations of TCE on the
      wettability of sandstone.
AB  - The wettability of aquifer rocks is a key physical parameter which exerts an
      important control on the transport, residual trapping, distribution and eventual
      fate of chlorinated hydrocarbon solvents (CHSs) released into the subsurface.
      Typically chlorinated solvents are assumed to be non-wetting in water saturated
      rocks and unconsolidated sediments. However industrially formulated solvent
      products are often combined with basic additives such as alkylamines to improve
      their performance; and the mineral surfaces of aquifer rocks and sediments
      usually possess a range of acid and hydrogen-bonding adsorption sites. The
      presence of these sites provides a mechanism whereby the basic additives in CHSs
      can be adsorbed at the solvent phase/solid phase interface. Given the amphiphilic
      molecular structure of these additives, this may result in changes in the wetting
      conditions of the solid phase. The aim of this study was therefore to test this
      conjecture for two classes of additives (alkylamines and quaternary ammonium
      salts) that are often encountered in industrial solvent formulations. Wettability
      assessments were made on sandstone cores by means of measurements of spontaneous
      and forced water drainage and spontaneous and forced water imbibition and through
      contact angle measurements on a smooth quartz surface. No solvent/additive
      combination produced solvent wetting conditions, though dodecylamine and
      octadecylamine significantly reduced the water wetting preference of sandstone
      which frequently resulted in neutral wetting conditions. The large volume of
      spontaneous water drainage observed in wettability experiments involving
      cetyltrimethylammonium bromide and octadecyltrimethylammonium bromide, suggested
      that the sandstone cores in these tests remained strongly water wetting. However
      equilibrium static contact angles of around 60 degrees were measured on quartz
      suggesting that the sandstone surfaces should be close to neutral wetting
      conditions. This paradox was finally resolved by noting that contact between the
      solvent mixture and water in the sandstone core resulted in a final solvent phase
      which had an extremely low interfacial tension. It is therefore suspected that
      the observed spontaneous drainage of solvent from the core was driven by
      gravitational and buoyancy forces rather than strong water wetting conditions.
      Finally it was noted that the mobilisation of iron oxide coatings from the
      sandstone surface had a considerable influence in reducing the interfacial
      tension and in the formation and stabilisation of TCE/water emulsions.

PMID- 16099535
TI  - An active region model for capturing fractal flow patterns in unsaturated soils:
      model development.
AB  - Preferential flow commonly observed in unsaturated soils allows rapid movement of
      solute from the soil surface or vadose zone to the groundwater, bypassing a
      significant volume of unsaturated soil and increasing the risk of groundwater
      contamination. A variety of evidence indicates that complex preferential patterns
      observed from fields are fractals. In this study, we developed a relatively
      simple active region model to incorporate the fractal flow pattern into the
      continuum approach. In the model, the flow domain is divided into active and
      inactive regions. Flow occurs preferentially in the active region (characterized
      by fractals), and inactive region is simply bypassed. A new constitutive
      relationship (the portion of the active region as a function of saturation) was
      derived. The validity of the proposed model is demonstrated by the consistency
      between field observations and the new constitutive relationship.

PMID- 16099536
TI  - Is your phone bugged? The incidence of bacteria known to cause nosocomial
      infection on healthcare workers' mobile phones.

PMID- 16099537
TI  - Use of hydrogen peroxide vapour for environmental control during a Serratia
      outbreak in a neonatal intensive care unit.

PMID- 16099538
TI  - Effectiveness of installing an antibacterial filter at water taps to prevent
      Legionella infections.

PMID- 16099539
TI  - Surveillance of hospital-acquired infections based on electronic hospital
      registries.
AB  - Computer-assisted surveillance of hospital-acquired infections (HAIs) was
      compared with conventional manual registration (our gold standard i.e. reference
      method) by chart reviews of nosocomial infections in patients from surgical and
      medical departments. By combining selected infection parameters from various
      electronic hospital registries, the computer detected general HAIs with a
      sensitivity of 94% and a specificity of 47%. However, defining septicaemia,
      urinary tract infection (UTI), pneumonia and postoperative wound infection (PWI)
      specifically by sets of simplified criteria (infection parameters), computer
      assisted surveillance was able to detect these infections with a sensitivity
      ranging between 82% (UTI) and 100% (septicaemia), and a specificity ranging
      between 91% (PWI) and 100% (septicaemia) compared with conventional manual
      registration. We conclude that computer surveillance based on data collected for
      other purposes in electronic hospital registries is an effective method for
      monitoring HAIs.

PMID- 16099540
TI  - A strategy to reduce MRSA colonization of stethoscopes.

PMID- 16099541
TI  - Could hospital patients' hands constitute a missing link?
AB  - The relationship between contamination of patients' hands and transmission of
      healthcare-associated infection has received only limited attention, but may
      represent a previously overlooked but potentially significant link in the chain
      of infection. This paper aims critically to review the literature to determine
      whether this possible epidemiological relationship is worthy of further
      consideration. Studies that have investigated the microbiology or hand hygiene
      behaviours of patients and other groups are examined to establish their
      limitations and implications for future practice and research. Examples of
      healthcare-associated infections where improving patient hand hygiene may have a
      favourable impact on transmission, and how this might be achieved within the
      context of current UK health service initiatives, are discussed. It is
      recommended that systematic studies of the role of patients' hands in the chain
      of hospital infection should be undertaken.

PMID- 16099542
TI  - An audit of the use of side- and isolation room facilities in a UK teaching
      hospital.

PMID- 16099543
TI  - MRSA--the storm clouds gather.

PMID- 16099544
TI  - Emergence of linezolid-resistant enterococci in a neutropenic patient.

PMID- 16099545
TI  - Prevalence rate of positive tuberculin test among Thai hospital personnel: a
      summary.

PMID- 16099546
TI  - Tolerability of HIV postexposure prophylaxis among healthcare workers.

PMID- 16099547
TI  - Aeromonas septicaemia: an uncommon complication following placement of
      transhepatic biliary drainage devices in Europe.

PMID- 16099548
TI  - Administration of the anabolic androgenic steroid nandrolone decanoate affects
      substance P endopeptidase-like activity in the rat brain.
AB  - The effect of the anabolic androgenic steroid, nandrolone decanoate, on substance
      P endopeptidase-like activity was examined in adult male Sprague-Dawley rats.
      Nandrolone decanoate (15 mg/kg day) or oil vehicle (sterile arachidis oleum) were
      administered by intramuscular injections during 14 days. Substance P
      endopeptidase, a predominantly cytosolic enzyme, generates the bioactive N
      terminal fragment substance P(1-7) from the enzyme substrate substance P.
      Nandrolone decanoate significantly reduced the substance P endopeptidase-like
      activity compared to control animals in hypothalamus (43% reduction), caudate
      putamen (44%), substantia nigra (32%) and the ventral tegmental area (27%). It
      was previously reported that both hypothalamus and caudate putamen contained
      significantly higher levels of substance P after nandrolone administration. The
      higher concentration of substance P in these regions could to an extent be
      attributed to the reduction in substance P endopeptidase-like activity. This
      result elucidates the important role of peptidase activity in the regulation of
      the substance P transmitter system. The present study provides additional support
      for the hypothesis that alterations in the substance P system in certain brain
      areas may contribute to some of the personality changes reported in connection
      with AAS abuse.

PMID- 16099549
TI  - NR1, NR2A and NR2C subunits expression after cervical spinal cord transplant and
      section in dogs.
AB  - This paper served to evaluate the expression levels of subunits NR1, NR2A and
      NR2C which are implicated in neuronal plasticity events. A 50% (right half) 4 mm
      longitudinal resection of the spinal cord was done at the C5-C6 level with
      preservation of the anterior spinal artery. This was effected in a dog model
      after either a homologous transplant or a pure spinal cord section. In this study
      we used two groups of dogs with four individuals each, as well as a control
      group. The transplant group (n=4) was analyzed at days 3 and 28 post surgery. The
      section group (n=4) was also analyzed at days 3 and 28 post op. All three groups
      (transplant, section and control) were evaluated as to the subunit expression in
      each of the segments corresponding to the transplanted or sectioned sites, the
      site contralateral to the transplanted or sectioned sites at levels half a
      centimeter both proximal and distal to the site of transplant and section. The
      results showed a variety of changes in each of the subunits depending on the
      group, the segment and the time of evaluation (acute versus chronic). This could
      be closely related to mechanisms which participate in regeneration and functional
      recuperation.

PMID- 16099550
TI  - Is M129V of PRNP gene associated with Alzheimer's disease? A case-control study
      and a meta-analysis.
AB  - The methionine/valine (M/V) polymorphism at codon 129 within the prion protein
      gene (PRNP) represents a known risk factor for Creutzfeldt-Jakob disease (CJD).
      Few authors reported also the effects of this polymorphism on the risk of
      Alzheimer's disease (AD), although with controversial results. To better clarify
      this issue, we performed a novel case-control study and a meta-analysis of
      published association studies between PRNP and AD. Our findings argue against
      PRNP as a susceptibility gene for developing AD in the Italian population but
      support the hypothesis that the V allele influences cognitive performances. The
      meta-analysis, revealed that Caucasian subjects homozygous at codon 129 had a 1.3
      fold increased risk [95% CI: 1.0-1.6, p = 0.05] of developing AD compared to
      heterozygous individuals. We also observed that MM genotype and M allele
      represent a risk factor for AD, independently from the ethnic background,
      providing a significant but modest association between this polymorphism and AD.

PMID- 16099551
TI  - Standards for education and training for interagency working in child protection
      in the UK: implications for nurses, midwives and health visitors.
AB  - This article presents a discussion of key issues for the education of nurses,
      midwives and health visitors following the completion of a Department of Health
      funded project, managed by the General Social Care Council and conducted jointly
      by two research centres; Salford Centre for Social Work Research and Salford
      Centre for Nursing, Midwifery and Collaborative Research. The work was initiated
      in response to Lord Laming's report on the circumstances leading to the death of
      Victoria Climbie. The project was conducted in relation to specified professions
      and occupational groups: doctors; health visitors; midwives; nurses; police;
      teachers, and social workers. It was undertaken in two stages. The first stage
      mapped existing material about standards in relation to education and training
      for interagency working. The second stage engaged in an extensive consultation
      exercise through which a model and a set of proposed standards for interagency
      education and training for interagency work were developed. The former is
      detailed fully in this report, while nine examples of standards are presented.
      The project final report was presented seven months after commencement.

PMID- 16099552
TI  - Home parenteral nutrition: a qualitative interview study of the experiences of
      advanced cancer patients and their families.
AB  - BACKGROUND & AIM: The benefit of home parenteral nutrition (HPN) to advanced
      cancer patients is often debated and an evidence-base for parenteral nutrition
      (PN) in palliative care is lacking. The aim of this study is to investigate the
      experiences of HPN from the perspective of advanced cancer patients and their
      family members. METHODS: Semi-structured interviews were conducted with 13
      advanced cancer patients with experience of HPN and 11 family members. The
      qualitative data was analyzed inductively using constant comparison. RESULTS: The
      most salient positive feature of HPN was a sense of relief and security that
      nutritional needs were met. This was said to have a direct and positive effect on
      quality of life and on body weight, level of energy, strength, and activity.
      Positive statements about HPN were often coupled to the benefits of being
      enrolled in advanced home care. The most salient negative effect of HPN described
      was related to restrictions in family life and social contacts for the whole
      family. However, benefits of the HPN treatment were generally said to outweigh
      negative aspects. CONCLUSION: This study indicates that the interviewed cancer
      patients and their family members experienced physical, social and psychological
      benefits from HPN treatment.

PMID- 16099553
TI  - Highly conserved pattern of recognition of influenza A wild-type and variant CD8+
      CTL epitopes in HLA-A2+ humans and transgenic HLA-A2+/H2 class I-deficient mice.
AB  - As an in vivo model for studying human MHC (HLA) class I-restricted CTL responses
      to viral infection, we established a series of HLA Tg mice expressing HLA-A2, -B7
      or -B27 human/mouse hybrid genes on a background deficient for H2 class I (Tg
      HLA(hyb)/H2 class I DKO). To determine whether CTL recognition of influenza A
      (flu) infection in Tg HLA-A2(hyb)/H2 DKO mice is similar to HLA-A2+ humans, we
      compared the HLA-A2-restricted Tg mouse and human CD8+ T-cell responses to an
      immunodominant flu epitope (wild-type [WT] M1 58-66), as well as a variant of
      this peptide (var. M1 58-66). Similar to HLA-A2+ humans, our results show WT M1
      58-66 is likely the dominant CTL epitope recognized in infected Tg HLA-A2(hyb)/H2
      DKO mice. Var. M1 58-66 was also recognized by WT peptide-reactive T cells from
      both HLA-A2+ humans and Tg mice, although slightly less efficiently than WT M1 58
      66 in both cases. Reduced variant recognition was shown to be associated with
      reduced peptide/A2 binding, as well as a more limited repertoire of utilized TCR
      Vbeta chains. The similar pattern of recognition and cross reaction observed here
      for the WT and variant M1 58-66 epitopes with HLA-A2 by human and Tg HLA mouse
      CTLs indicates that A2-dependent events of Ag processing, presentation and
      recognition are well-conserved between species. These findings demonstrate that
      this Tg HLA-A2/H2 DKO model will aid identification and development of epitopes
      as vaccines for numerous viral and tumor antigens for the HLA-A2 supertype.

PMID- 16099554
TI  - The jejunal Peyer's patches are the major inductive sites of the F4-specific
      immune response following intestinal immunisation of pigs with F4 (K88) fimbriae.
AB  - A recently developed oral immunisation model in pigs in which F4 (K88) fimbriae
      of enterotoxigenic Escherichia coli are administered to induce a protective
      intestinal immunity, was used to determine the optimal inductive sites of the F4
      specific intestinal immune response. Hereto, pigs were immunised with F4 orally,
      in the lumen of the mid-jejunum, ileum or mid-colon. Throughout the small
      intestine, the highest number of ASC was found following jejunal immunisation,
      followed by ileal, oral and colonic immunisation. To determine the signifance of
      Peyer's patches in the induced immune response, F4 was injected into the jejunal
      Peyer's patches (JPP), lamina propria (LP) and ileal Peyer's patches (IPP).
      Immunisation in the JPP induced the highest number ASC in the small intestine,
      whereas immunisation in the LP and IPP resulted in lower intestinal antibody
      responses. In conclusion, we have shown that the JPP are the major inductive
      sites of the F4-specific intestinal antibody response. This knowledge could be
      important when using the pig as an animal model for vaccination studies.

PMID- 16099555
TI  - Mucosal and systemic immunization elicited by Newcastle disease virus (NDV)
      transgenic plants as antigens.
AB  - As a step towards developing a safe and effective edible vaccine against
      Newcastle disease virus (NDV), we have explored the use of plants genetically
      engineered to express viral proteins. We report the construction of transgenic
      potato plants expressing the genes coding for immunogenic proteins of NDV under
      the regulation of CaMV 35S promoter and its immunogenicity in mice. All mice
      receiving transgenic plant extracts in incomplete Freund adjuvant produced
      specific anti-NDV antibodies. Animals fed with transgenic leaves showed a
      specific response against NDV. Detection of IgA released from in vitro-cultured
      intestinal tissue fragments indicated the presence of IgA-secreting cells in the
      gut.

PMID- 16099556
TI  - Use of a craniotome for harvesting osteocutaneous scapular free flaps.

PMID- 16099557
TI  - Blindness following retrobulbar haemorrhage--it can be prevented.
AB  - Delay in diagnosis and treatment of an elderly woman with a malar fracture that
      caused retrobulbar haemorrhage resulted in complete loss of vision in the right
      eye.

PMID- 16099558
TI  - Three-year review of facial fractures at a teaching hospital in northern Iran.
AB  - During the three years March 2001-February 2004, 7200 patients with maxillofacial
      trauma were seen at Poorsina Hospital, of whom 2160 had 4752 fractures of facial
      bones, 3089 (65%) mainly mandibular and 1663 (35%) mainly midfacial. Road traffic
      collisions accounted for the injuries in 6552 of the 7200 patients (91%), falls
      in 396 patients (5.5%), assault in 208 (2.9%) and sport and other causes in 44
      (0.6%). The male (n=6646) to female (n=554) ratio was 12:1. During summer,
      Iranian weekends (Thursdays-Fridays) and the Iranian new year (begins on 21
      March), the incidence was much higher than at other times.

PMID- 16099559
TI  - A simple clinical test of flexor pollicis longus rupture.
AB  - Rupture of the tendon of flexor pollicis longus is suspected when active flexion
      of the interphalangeal joint of the thumb is not possible. This can be a result
      of trauma but, when spontaneous, diagnostic confusion can exist as incomplete
      palsy of the anterior interosseous nerve can present in a similar way. We
      describe a simple clinical sign which can differentiate between these conditions.

PMID- 16099560
TI  - Lac Dufault sediment core trace metal distribution, bioavailability and toxicity
      to Hyalella azteca.
AB  - To determine changes in metal distribution, bioavailability and toxicity with
      sediment depth, two 20-cm-long replicate cores were collected from a lake
      historically subjected to the influence of metal mining and smelting activity.
      The vertical distribution of Pb, Cd and Cu in sediment was similar for all three
      metals, with the surface layers showing enrichment and the deeper (pre
      industrial) layers showing lower concentrations. Toxicity of each sediment core
      section was determined in laboratory tests with the freshwater amphipod Hyalella
      azteca. Bioavailable metal in each sediment slice was estimated from metal
      concentrations in overlying water in these toxicity tests and, for Cd, also from
      metal bioaccumulation. The profile for Cd in tissue was comparable to Cd in
      sediment and overlying water, but relative Cd bioavailability from sediment
      increased with sediment depth. Survival increased with increasing sediment depth,
      suggesting that surface sediments were probably less or non-toxic before
      industrialization.

PMID- 16099561
TI  - Tissues and hair residues and histopathology in wild rats (Rattus rattus L.) and
      Algerian mice (Mus spretus Lataste) from an abandoned mine area (Southeast
      Portugal).
AB  - Data gathered in this study suggested the exposure of rats and Algerian mice,
      living in an abandoned mining area, to a mixture of heavy metals. Although
      similar histopathological features were recorded in the liver and spleen of both
      species, the Algerian mouse has proved to be the strongest bioaccumulator
      species. Hair was considered to be a good biological material to monitor
      environmental contamination of Cr in rats. Significant positive associations were
      found between the levels of this element in hair/kidney (r=0.826, n=9, p<0.01)
      and hair/liver (r=0.697, n=9, p=0.037). Although no association was found between
      the levels of As recorded in the hair and in the organs, the levels of this
      element recorded in the hair, of both species, were significantly higher in
      animals captured in the mining area, which met the data from the organs analysed.
      Nevertheless, more studies will be needed to reduce uncertainty about cause
      effect relationships.

PMID- 16099562
TI  - Radionuclides, heavy metals and fluorine incidence at Tapira phosphate rocks,
      Brazil, and their industrial (by) products.
AB  - Inorganic phosphate fertilizers may contain radionuclides, heavy metals and
      fluorine. This paper presents the possible environmental hazards from Tapira
      phosphate rocks and their (by) products (Brazil) utilized as phosphate
      fertilizers. The activity concentration of 238U, 234U, 226Ra and 40K in Tapira
      phosphate rocks is within the world range for these rock types. The 232Th
      activity concentration is higher than the mean reported in phosphate rocks. A
      value of 2184 nGy h(-1) was obtained for the exposure dose rate in Tapira
      phosphate deposit area, which is indicative of a high background radiation area.
      The flotation-separation process causes the incorporation of no more than 9%, 11%
      and 24% of radionuclides, heavy metals and fluorine, respectively, into the
      phosphate concentrate. The radionuclides and heavy metals existing in phosphate
      fertilizers applied in Brazilian crops according to the recommended rates, do not
      raise their concentration in soils to harmful levels.

PMID- 16099563
TI  - Personality and eating disorders: a decade in review.
AB  - Personality traits have been implicated in the onset, symptomatic expression, and
      maintenance of eating disorders (EDs). The present article reviews literature
      examining the link between personality and EDs published within the past decade,
      and presents a meta-analysis evaluating the prevalence of personality disorders
      (PDs) in anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder
      (BED) as assessed by self-report instruments versus diagnostic interviews. AN and
      BN are both consistently characterized by perfectionism, obsessive
      compulsiveness, neuroticism, negative emotionality, harm avoidance, low self
      directedness, low cooperativeness, and traits associated with avoidant PD.
      Consistent differences that emerge between ED groups are high constraint and
      persistence and low novelty seeking in AN and high impulsivity, sensation
      seeking, novelty seeking, and traits associated with borderline PD in BN. The
      meta-analysis, which found PD rates of 0 to 58% among individuals with AN and BN,
      documented that self-report instruments greatly overestimate the prevalence of
      every PD.

PMID- 16099564
TI  - Application of the threshold of toxicological concern concept to pharmaceutical
      manufacturing operations.
AB  - A scientific rationale is provided for estimating acceptable daily intake values
      (ADIs) for compounds with limited or no toxicity information to support
      pharmaceutical manufacturing operations. These ADIs are based on application of
      the "thresholds of toxicological concern" (TTC) principle, in which levels of
      human exposure are estimated that pose no appreciable risk to human health. The
      same concept has been used by the US Food and Drug Administration (FDA) to
      establish "thresholds of regulation" for indirect food additives and adopted by
      the Joint FAO/WHO Expert Committee on Food Additives for flavoring substances. In
      practice, these values are used as a statement of safety and indicate when no
      actions need to be taken in a given exposure situation. Pharmaceutical
      manufacturing relies on ADIs for cleaning validation of process equipment and
      atypical extraneous matter investigations. To provide practical guidance for
      handling situations where relatively unstudied compounds with limited or no
      toxicity data are encountered, recommendations are provided on ADI values that
      correspond to three categories of compounds: (1) compounds that are likely to be
      carcinogenic, (2) compounds that are likely to be potent or highly toxic, and (3)
      compounds that are not likely to be potent, highly toxic or carcinogenic.
      Corresponding ADIs for these categories of materials are 1, 10, and 100
      microg/day, respectively.

PMID- 16099565
TI  - Probabilistic risk characterization: an example with di(2-ethylhexyl) phthalate.
AB  - While probabilistic methods gain attention in hazard characterization and are
      increasingly used in exposure assessment, full use of the available probabilistic
      information in risk characterization is still uncommon. Usually, after
      probabilistic hazard characterization and/or exposure assessment, percentiles
      from the obtained distributions are used as point estimates in risk
      characterization. In this way, all information on variability and uncertainty is
      lost, while these aspects are crucial in any risk assessment. In this paper, we
      present a method to integrate the entire distributions from probabilistic hazard
      characterization and exposure assessment into one risk characterization plot.
      This method is illustrated using di(2-ethylhexyl) phthalate as an example. The
      final result of this probabilistic risk assessment is summarized in a single
      plot, containing two pieces of information: the confidence we may have in
      concluding there is no risk, and the fraction of the population this conclusion
      applies to. This information leads to a better informed conclusion on the risk of
      a substance, and may be very useful to define the necessary measures for risk
      reduction.

PMID- 16099566
TI  - Effects of single and repeated exposure to biocidal active substances on the
      barrier function of the skin in vitro.
AB  - The dermal route of exposure is important in worker exposure to biocidal
      products. Many biocidal active substances which are used on a daily basis may
      decrease the barrier function of the skin to a larger extent than current risk
      assessment practice addresses, due to possible skin effects of repeated exposure.
      The influence of repeated and single exposure to representative biocidal active
      substances on the skin barrier was investigated in vitro. The biocidal active
      substances selected were alkyldimethylbenzylammonium chloride (ADBAC), boric
      acid, deltamethrin, dimethyldidecylammonium chloride (DDAC), formaldehyde,
      permethrin, piperonyl butoxide, sodium bromide, and tebuconazole. Of these nine
      compounds, only the quaternary ammonium chlorides ADBAC and DDAC had a clear and
      consistent influence on skin permeability of the marker compounds tritiated water
      and [(14)C]propoxur. For these compounds, repeated exposure increased skin
      permeability more than single exposure. At high concentrations the difference
      between single and repeated exposure was quantitatively significant: repeated
      exposure to 300 mg/L ADBAC increased skin permeability two to threefold in
      comparison to single exposure. Therefore, single and repeated exposure to
      specific biocidal products may significantly increase skin permeability,
      especially when used undiluted.

PMID- 16099567
TI  - Immune assessments in developmental and juvenile toxicology: practical
      considerations for the regulatory safety testing of pharmaceuticals.
AB  - The developing organism is considered to be more sensitive than the adult to
      immunotoxic agents. There is every reason, therefore, to include immune
      assessments in the regulatory testing for developmental toxicity of drugs that
      are intended to be used in young patients or pregnant woman. An effective
      strategy would be to incorporate immune assessments in the existing
      recommendations on pre- and post-natal toxicity study in the rat from the
      International Conference on Harmonisation. Immune assessments could also be
      included in juvenile toxicity studies to screen for effects resulting from post
      natal exposure to the drug. Adequate testing methods are available to screen for
      developmental effects that result in immune depression. Routine immune
      assessments may comprise histopathological examination of the lymphoid
      organs/tissues and immunophenotyping of lymphocyte subsets in the blood, spleen,
      or thymus. These tests should be performed in rodents at various ages and at
      various stages of pre- and post-weaning development. Immunoglobulin and cytokine
      measurements, assessment of the T-cell dependent antigen response to sheep red
      blood cells or keyhole limpet haemocyanin antigens, and host resistance studies
      may be performed as apical tests at maturity. More research is required to
      develop methods for the detection of drugs that may render the developing
      organism more susceptible to hypersensitivity or autoimmunity.

PMID- 16099568
TI  - Cancer dose--response assessment for acrylonitrile based upon rodent brain tumor
      incidence: use of epidemiologic, mechanistic, and pharmacokinetic support for
      nonlinearity.
AB  - A cancer dose-response assessment was conducted for acrylonitrile (AN) using
      updated information on mechanism of action, epidemiology, toxicity, and
      pharmacokinetics. Although more than 10 chronic bioassays indicate that AN
      produces multiple tumors in rats and mice, a number of large, well-conducted
      epidemiology studies provide no evidence of a causal association between AN
      exposure and cancer mortality of any type. The epidemiological data include early
      industry exposures that are far higher than occur today and that approach or
      exceed levels found to be tumorigenic in animals. Despite the absence of positive
      findings in the epidemiology data, a dose-response assessment was conducted for
      AN based on brain tumors in rats. Mechanistic studies implicate the involvement
      of oxidative stress in rat brain due to a metabolite (2-cyanoethylene oxide or
      CEO, cyanide), but do not conclusively rule out a potential role for the direct
      genotoxicity of CEO. A PBPK model was used to predict internal doses (peak CEO in
      brain) for 12 data sets, which were pooled together to provide a consistent
      characterization of the dose-response relationship for brain tumor incidence in
      the rat. The internal dose corresponding to a 5% increase in extra risk (ED
      05=0.017 mg/L brain) and its lower confidence limit (LED 05=0.014 mg/L brain) was
      used as the point of departure. The weight-of-evidence supports the use of a
      nonlinear extrapolation for the cancer dose-response assessment. A quantitative
      comparison of the epidemiology exposure-response data (lung and brain cancer
      mortality) to the rat brain tumor data in terms of internal dose adds to the
      confidence in the nonlinear extrapolation. Uncertainty factors of 200 and 220
      (for the oral and inhalation routes, respectively) were applied to the LED 05 to
      account for interspecies variation, intraspecies variation, and the severity of
      the response measure. Accordingly, oral doses below 0.009 mg/kg-day and air
      concentrations below 0.1mg/m(3) are not expected to pose an appreciable risk to
      human populations exposed to AN.

PMID- 16099569
TI  - Use of benchmark dose and meta-analysis to determine the most sensitive endpoint
      for risk assessment for dimethoate.
AB  - A meta-analysis of several rat toxicity studies for dimethoate was conducted to
      determine the most sensitive endpoint for use in risk assessment. The analysis
      was motivated by a recent developmental neurotoxicity (DNT) study, which
      identified the same no observed adverse effect level (NOAEL) for pup mortality
      and cholinesterase inhibition. The pup mortality NOAEL was lower than that
      determined in a range-finding study for the DNT and other reproduction studies,
      and was highly influenced by a single total litter loss in the middle dose group,
      which made interpretation difficult. First, a meta-analysis was conducted of four
      recent studies by gavage dosing with very similar designs, including the DNT.
      Benchmark dose (BMD) modeling was used to determine the appropriate point of
      departure for regulatory purposes, the lower limit of the BMD for a 5% incidence
      for pup mortality (BMDL(5)) and the lower limit of a 10% inhibition of brain
      cholinesterase (BMDL(10)*), the asterisk denotes that the BMD is based on
      continuous response variable as opposed to an incidence level. For pup mortality,
      the BMDL(5) for post-natal days (PND) 1-4 was 0.64 mg/kg/day. For cholinesterase
      inhibition, the lowest BMDL(10)* was 0.19 mg/kg/day for the dams at gestation day
      20. These results show that the regulatory point-of-departure for cholinesterase
      inhibition is more than threefold lower than pup mortality. Thus, risk
      assessments protecting against cholinesterase inhibition are likely to also be
      protective of pup mortality. In addition, cholinesterase inhibition and pup
      mortality were evaluated in two 2-generation reproduction studies by dietary
      exposure. Also, cholinesterase inhibition was evaluated in a 28-day dietary
      study. Dietary exposure is more relevant than gavage exposures for many human
      risk assessment scenarios. There was no consistent pup mortality at the highest
      doses of the two 2-generation dietary studies (6.0 and 6.5mg/kg/day). The average
      BMD(10)s for brain cholinesterase inhibition for the 2-generation studies was
      0.65 mg/kg/day, with a range of 0.49--0.96 mg/kg/day. This suggests that
      cholinesterase inhibition is at least a 10-fold more sensitive endpoint than pup
      mortality for dietary exposures. For the 28-day dietary study, the BMD(10) for
      brain cholinesterase inhibition was 1.1mg/kg/day for males and 0.70 mg/kg/day for
      females. The exposure duration in the 28-day dietary study is closest to the
      durations in the gavage studies. Compared to the dams in the gavage studies,
      which had a BMDL(10) of 0.19 mg/kg/day, the animals were more than threefold more
      sensitive to cholinesterase inhibition by gavage compared to dietary exposure.

PMID- 16099570
TI  - Ensuring quality of in vitro alternative test methods: issues and answers.
AB  - Many in vitro and ex vivo methods have been developed or are under development to
      reduce or replace animal usage in toxicity tests. Consistent with the goal of
      obtaining scientifically sound test data for hazard and risk assessment of
      chemicals, changes are being made in current policies and procedures to
      facilitate the acceptance of data developed using these methods. National and
      international organizations are developing policies and standards for scientific
      practice to assure quality in implementation of in vitro methods. Consensus is
      developing in the scientific community for the quality control measures needed
      for in vitro methods; including appropriate controls, data reporting elements,
      and benchmarks to be identified in test guidelines so that the potential risks of
      chemicals can be reviewed and reliably assessed. Additional guidance to the
      OECD's Good Laboratory Practice principles [Organization for Economic Cooperation
      and Development (. Advisory Document of the Working Group on Good Laboratory
      Practice: The Application of the Principles of GLP to in vitro Studies. OECD
      Series on Principles of Good Laboratory Practice and Compliance Monitoring Number
      14 (ENV/JM/MONO(2004)26). Paris, France] will help to ensure that in vitro tests
      used for regulatory purposes are reproducible, credible, and acceptable. Generic
      test guidelines incorporating performance standards are being written to allow
      acceptance of proprietary test methods by regulatory agencies and to provide
      assurance that any in vitro system performs over time in a manner that is
      consistent with the test system as it was originally validated.

PMID- 16099571
TI  - Classification of man-made vitreous fibers: Comments on the revaluation by an
      IARC working group.
AB  - In 2001, an IARC working group revaluated the carcinogenic risks of man-made
      vitreous fibers (MMVF). Compared with the IARC evaluation in 1987, the overall
      evaluations of insulation glass wool, rock (stone) wool, and slag wool were
      changed from Group 2B to Group 3. These changes ensued from an alteration in the
      evidence for cancer in humans and in experimental animals: Instead of
      "sufficient," the evidence for cancer in experimental animals is now looked upon
      as "limited" if there is a carcinogenic response after intraperitoneal injection
      but not after recently conducted inhalation experiments. For these studies, it is
      argued that they did properly address the technological limitations of earlier
      inhalation experiments. For Maxim and McConnell [Maxim L.D., McConnell E.E.,
      2001. Interspecies comparisons of the toxicity of asbestos and synthetic vitreous
      fibers: a weight-of-the-evidence approach. Regul. Toxicol. Pharmacol. 33, 319
      342], well-conducted inhalation studies are very sensitive and rats may be more
      sensitive than humans in detecting the carcinogenic potential of MMVF. However,
      their arguments are highly questionable. The explanations of the IARC working
      group for preferring the newer inhalation studies are not sufficiently supported
      by the published data. Having in mind the higher sensitivity of humans compared
      to rats after inhalation of asbestos, more emphasis should have been given to the
      carcinogenic response after intraperitoneal injection.

PMID- 16099572
TI  - Epidemiologic studies of chrome and cancer mortality: a series of meta-analyses.
AB  - We used 49 epidemiologic studies based on 84 papers published since 1950 to
      develop an array of meta-analyses relating exposure to chrome-six compounds with
      10 causes of death. Most exposures occurred in occupational settings. Studies
      were assessed for quality, and for control of smoking or economic status if they
      related to lung or stomach cancer. There was no excess mortality from all causes
      combined among chrome-exposed persons. A minimal excess of cancer (SMR=112),
      overall, was due primarily to an excess of lung cancer (SMR=141) but the SMR was
      112 among the better-quality, smoking-controlled studies. The overall SMR for
      stomach cancer was 113 but it was 82 among the studies that were controlled for
      economic status. Findings were unremarkable for the six other cancers evaluated:
      prostate, kidney, and central nervous system cancer and leukemia, Hodgkin's
      disease and other lymphatohematopoietic cancer. This series of meta-analyses
      indicates that chrome-six is a weak cause of lung cancer and is not a cause of
      any of the other seven forms of cancer evaluated.

PMID- 16099573
TI  - Experiences of stigma and access to HAART in children and adolescents living with
      HIV/AIDS in Brazil.
AB  - This study describes and conceptualizes the experiences of stigma in a group of
      children living with HIV in Sao Paulo, Brazil, and evaluates the impact of access
      to highly active antiretroviral therapy (HAART) over the social course of AIDS
      and over the children's experiences of stigma. Through ethnographic research in
      Sao Paulo from 1999 to 2001, the life trajectories of 50 children ages 1-15
      living with or affected by HIV were studied. Data were collected via participant
      observation and semi-structured informal interviews and analyzed using social
      theories on illness experience and social inequality. Our results demonstrate
      that AIDS-related stigma occurs within complex discrimination processes that
      change as children reach adolescence. We found that structural violence in the
      forms of poverty, racism, and inequalities in social status, gender, and age
      fuels children's experiences of stigma. We also describe how access to HAART
      changes the lived experience of children, reduces stigma, and brings new
      challenges in AIDS care such as adolescents' sexuality and treatment adherence.
      Based on these results, we propose structural violence as the framework to study
      stigma and argue that interventions to reduce stigma that solely target the
      perception and attitudes toward people living with HIV are limited. In contrast
      universal access to HAART in Brazil is a powerful intervention that reduces
      stigma, in that it transforms AIDS from a debilitating and fatal disease to a
      chronic and manageable one, belongs to a broader mechanism to assure citizens'
      rights, and reduces social inequalities in access to health care.

PMID- 16099574
TI  - What are the economic consequences for households of illness and of paying for
      health care in low- and middle-income country contexts?
AB  - This paper presents the findings of a critical review of studies carried out in
      low- and middle-income countries (LMICs) focusing on the economic consequences
      for households of illness and health care use. These include household level
      impacts of direct costs (medical treatment and related financial costs), indirect
      costs (productive time losses resulting from illness) and subsequent household
      responses. It highlights that health care financing strategies that place
      considerable emphasis on out-of-pocket payments can impoverish households. There
      is growing evidence of households being pushed into poverty or forced into deeper
      poverty when faced with substantial medical expenses, particularly when combined
      with a loss of household income due to ill-health. Health sector reforms in LMICs
      since the late 1980s have particularly focused on promoting user fees for public
      sector health services and increasing the role of the private for-profit sector
      in health care provision. This has increasingly placed the burden of paying for
      health care on individuals experiencing poor health. This trend seems to continue
      even though some countries and international organisations are considering a
      shift away from their previous pro-user fee agenda. Research into alternative
      health care financing strategies and related mechanisms for coping with the
      direct and indirect costs of illness is urgently required to inform the
      development of appropriate social policies to improve access to essential health
      services and break the vicious cycle between illness and poverty.

PMID- 16099575
TI  - Health selection in a 14-year follow-up study--a question of gendered
      discrimination?
AB  - Health selection, as one of the several possible explanations for social
      inequities in health, has been receiving more attention recently but few
      researchers turn the issue into a question of discrimination. The aim of the
      study was to analyse the impact of health in young age for social position in
      adult age and to discuss health selection in terms of discrimination from a
      gender-theoretical perspective. A prospective cohort study was conducted, in
      which all pupils (N = 1083) in the last year of compulsory school in a middle
      sized municipality in northern Sweden were followed for 14 years. The response
      rate was high, with 96.6% still participating after 14 years. The data were
      collected through repeated comprehensive self-administered questionnaires as well
      as through teacher interviews and register data. Health selection was analysed in
      a multiple logistic regression model, with working-class position at age 30 as a
      dependent variable and different measures of health/health behaviour at age 16
      and 21 as independent variables. Overall, the impact of early health/health
      behaviour on future socioeconomic position was small or non-existent. However,
      even after correction for possible mediating and moderating mechanisms, being
      overweight at age 16 and at age 21 was related to future working-class position
      among women only. Possible mediating mechanisms were feeling looked down upon,
      not being active in associations and not reading cultural/political events in
      daily newspapers. Early menarche together with early motherhood and low education
      could not explain the correlations. Our results indicate that overweight girls
      and young women are exposed to gendered discrimination which probably occurs in
      many arenas, based on the societal norms for female bodies in our society. There
      is a need to redirect research on health selection into gender research in order
      to further explore the subject as well as the possible mechanisms of gendered
      discrimination.

PMID- 16099576
TI  - Marital transitions and mental health: are there gender differences in the short
      term effects of marital status change?
AB  - Although there has been evidence to suggest that women exhibit more vulnerability
      to psychological distress than men when they lose a spouse or remarry, knowledge
      about the process by which men and women adjust to marital change remains
      fragmentary. This is due in part to the length of time between observations in
      longitudinal studies on marital change, with the result that mental health status
      is typically assessed long after a marital status transition has occurred. The
      purpose of the current study is to test for gender differences in the short-term
      mental health effects of a marital status transition using three waves of data
      collected at two year intervals in a Canadian population health survey
      (N=11,155). Growth curve analyses confirm the mental health advantage of marriage
      and reveal that the short-term effects of moving into and out of marriage on
      psychological distress are similar for men and women. We discuss the implications
      of these findings for resolving competing explanations regarding psychological
      adjustment to marital change.

PMID- 16099577
TI  - [The Omega "Omega" pulley plasty: a new technique for the surgical management of
      the De Quervain's disease].
AB  - The Omega "Omega" pulley plasty: a new technique for the surgical management of
      the De Quervain's disease. The De Quervain tenosynovitis is an inadequacy into
      the first extensor compartment between the osteo-fibrous tunnel and the tendons.
      This mechanical conflict generates a tenosynovitis of the extensor pollicis
      brevis and the abductor pollicis longus tendons. This is generally expressed by a
      tenderness on the radial side of the wrist over the radial styloid process. The
      medical management consists on corticoids infiltrations of the first extensor
      compartment, the avoidance of repetitive and stress movements of the first ray
      with the use of a rest splint. The surgical approach is considered with the
      recurrence of the painful symptoms. This well-known pathology is reputated to
      require a simple section of the pulley. Our post-operative complications have
      been reported in the literature of this classical surgical solution. These
      complications concern an incomplete release of the extensor pollicis brevis and
      the abductor pollicis longus tendons particularly when an extensor sub
      compartment exists and was overlooked, an irritation of the collateral branches
      of the sensitive radial nerve or the occurrence of a nevroma after a nerve injury
      and the most serious complication is a palmar subluxation of the extensor tendons
      which can occur with the thumb extended and the wrist flexed. In rare cases, this
      subluxation can be really painful and requires a surgical management with
      secondary reconstruction of the pulley. This reconstruction necessitates distal
      pedicle flaps from the dorsal retinaculum or the brachioradialis tendon. To
      prevent these complications, Codega and Kapandji described techniques of
      reconstruction of the pulley after its release. More recently, Le Viet reported a
      procedure using the anterior flap of the pulley; fixed to the dermis it will work
      as a barrier and maintain the tendons sliding on the radial styloid groove. These
      techniques require to divide the pulley and to reconstruct it suturing the
      different flaps. It can generate adherences between the extensor tendons, the
      overlying skin and the collateral branches of the radial nerve. The authors
      present a new and original plasty procedure of the first extensor compartment
      pulley, the "Omega" Omega plasty. It consists to liberate the anterior attachment
      of the pulley over the anterior lip of the styloid process respecting its
      continuity with the periosteum flap. This conservative procedure is very
      interesting; it permits enough expansion of the tunnel volume decompressing the
      extensor tendons as a treatment of the De Quervain disease and respecting the
      anatomy and the continuity of the osteo-fibrous tunnel. This technique is simple,
      reliable and respects the first ray extensor tendons gliding physiology and
      biodynamic. In spite of our short clinical experience with only ten cases, all
      the patients retrieve a normal function of the thumb with complete disappearance
      of the first ray tenderness and pain without any complications. These preliminary
      results are encouraging and push us to consider the "Omega" plasty as a first
      choice for the surgical treatment of the De Quervain tenosynovitis.

PMID- 16099578
TI  - Malignant melanoma of the uterine cervix.

PMID- 16099579
TI  - Antenatal detection and impact on outcome of congenital diaphragmatic hernia: a
      12-year experience in Auvergne, France.
AB  - OBJECTIVE: To evaluate the detection rate of prenatal diagnosis and its impact on
      outcome in congenital diaphragmatic hernia (CDH). STUDY DESIGN: We
      retrospectively studied 51 cases of CDH registered in the Auvergne area from
      January 1992 to December 2003 (Birth Defect Registry of Auvergne, Institut
      Europeen des Genomutations). Our main outcome measurements were the detection
      rate of prenatal diagnosis, the incidence and types of associated anomalies and
      outcome (termination of pregnancy, in utero fetal demise, neonatal death,
      survival at the time of registration). RESULTS: Twenty-nine cases of isolated CDH
      were identified of which 13 were detected prenatally (45%) at a mean gestational
      age of 26.1 weeks and 22 cases of CDH with associated anomalies with prenatal
      diagnosis of CDH or any associated anomaly in 16 (73%; p=0.03) at a mean
      gestational age of 23.9 weeks. In the prenatally detected group (29 cases), there
      was 1 (3%) in utero fetal death (IUFD), 17 (59%) terminations of pregnancy (TOP)
      and 11 (38%) live births with early neonatal death in 7 (24%) cases despite
      delivery in a tertiary care centre in 10/11 cases (four survivors=14%). Most of
      the undetected cases were isolated CDH (16/22=73%) of which 1 (5%) was a
      stillborn and 21 (95%) live births with 17 survivors (77%) although 15/21 (71%)
      were not born at the tertiary care centre (p=0.001). The overall survival rate
      was 41% with a large variability depending on associated anomalies and prenatal
      diagnosis (p<0.0001) (prenatally detected cases: 3/13 (23%) isolated CDH and 1/16
      (6%) CDH with associated anomalies; undetected cases: 13/16 (81%) isolated CDH
      and 4/6 (67%) CDH with associated anomalies). CONCLUSION: Prenatal diagnosis of
      CDH leads to the delivery of affected babies in tertiary care centres but it
      remains a challenge in particular for isolated CDH cases and it is associated
      with a lower survival rate. Associated anomalies contribute to prenatal
      detection, are related to a higher TOP rate but do not facilitate the detection
      of diaphragmatic defect per se.

PMID- 16099580
TI  - The term breech presentation: Neonatal results and obstetric practices in France.
AB  - OBJECTIVE: Compare neonatal complications according to the planned mode of
      delivery and according to whether the women gave birth at a maternity unit that
      applied "consensus" guidelines. STUDY DESIGN: The study used the database of the
      AUDIPOG Sentinel Network (n=71,919 pregnancies between 1994 and 2000). The
      principal outcome was a composite variable that included neonatal morbidity and
      mortality. A survey of obstetric practices was sent to 175 maternity units
      belonging to the network. Consensus guidelines were defined from the survey
      responses and taken into account in the database analysis. RESULTS: Neonatal
      complications did not differ between the group of women with term babies in
      breech presentation for whom vaginal delivery was planned and those for whom an
      elective caesarean was planned (adjusted OR=1.33; 95% CI: 0.63-2.80). The survey
      allowed us to define a set of six criteria for deciding on mode of delivery; it
      established a consensus, followed by 42% of the maternity units in the study. The
      rate of neonatal complications among the women with planned vaginal delivery was
      lower for those giving birth in units that applied the consensus guidelines than
      among those in the other units: adjusted OR=0.27 (95% CI: 0.09-0.85). CONCLUSION:
      The risk of neonatal morbidity according to planned mode of delivery for term
      breech babies was lower for those giving birth in units that applied the
      consensus guidelines than among those in the other units.

PMID- 16099581
TI  - Location of the uterine transverse incisions in patients with multiple repeat
      caesarean sections.

PMID- 16099582
TI  - Solitary fibrous tumor of the pelvis.

PMID- 16099583
TI  - The follow-up of acute disseminated encephalomyelitis in a comatose pregnant
      woman.

PMID- 16099584
TI  - Atypical neurological form of congenital toxoplasmosis after maternal
      seroconversion in the first trimester of pregnancy: severe manifestations at 2
      months of age.

PMID- 16099585
TI  - The molecular changes during placental detachment.
AB  - OBJECTIVES: RCAS1 is a membrane protein that plays a role in the maintenance of
      maternal immune tolerance during pregnancy. The work presented here demonstrates
      the results of RCAS1 expression in placenta in cases of placental abruption and
      patients with retained placental tissue during the third stage of labor. STUDY
      DESIGN: The placenta tissue samples were obtained during vaginal and cesarean
      delivery (derived from 117 pregnancies). Pregnant women were divided into four
      groups according to the onset of labor and the time of placental detachment in
      term labors. The samples were analyzed by the Western blot method. Statistical
      analysis was performed using the Shapiro-Wilk procedure. The Mann-Whitney test
      and Student's t-test were applied to compare the differences between parametric
      data. RESULTS: The average relative amount of RCAS1 observed in those patients
      with retained placental tissue was statistically significantly higher than in the
      patients with placental abruption. CONCLUSION: The differences observed in
      placental RCAS1 levels confirm the participation of this protein in the
      inhibition of maternal immune response during gestation. The present results also
      indicate that RCAS1 participates in the changes in the maternal immune system
      that take place during parturition and reinforce its potential involvement in the
      mechanism of placental abruption.

PMID- 16099586
TI  - Transdisciplinary training in reproductive health through online
      multidisciplinary problem-solving: a proof of concept.
AB  - OBJECTIVE: The problem of iatrogenic multiple pregnancies has been addressed
      through an online multidisciplinary discussion forum with the primary aim of
      developing a transdisciplinary research and training tool. STUDY DESIGN: The
      pedagogical approach was divided in three phases, unidisciplinary,
      multidisciplinary and multi/transdisciplinary. Evaluation of the level of
      transdisciplinarity reached by each of the students was based on their capacity
      to translate disciplinary knowledge, to establish a frank dialogue, to cross
      disciplinary barriers, to detach from their initial opinion, and to develop
      curiosity for others' perspectives and concerns. RESULTS: Translation of
      disciplinary knowledge and frank dialogue were easily performed by all. Most
      students showed curiosity towards the others' point of view and started to be
      preoccupied with the concerns of other students. CONCLUSION: Online discussion
      forum is a particularly well-adapted tool for transdisciplinary research and
      training.

PMID- 16099587
TI  - Dielectric properties of the collagen-glycosaminoglycans scaffolds in the
      temperature range of thermal decomposition.
AB  - Dielectric spectroscopy has been applied to study the decomposition process of
      unmodified collagen and chondroitin sulfate (CS)- and hyaluronic acid (HA)
      modified collagen. Measurements were performed over the frequency range from 10
      Hz to 100 kHz and at temperatures from 22 to 260 degrees C. According to the
      Kramers-Kronig relationship a dispersion is apparent in both epsilon' and
      epsilon'' for the three materials below 140 degrees C and at higher temperatures
      as a broad peak around 220-230 degrees C, respectively. The values of epsilon'
      and epsilon'' at the same temperature for constant frequency are higher in HA
      modified collagen than in the unmodified collagen. However, small differences are
      shown in these parameters between CS-modified collagen and unmodified collagen.
      The observed dispersion around 220-230 degrees C corresponds to the decomposition
      of unmodified and CS- and HA-modified collagen. Power-low responses are observed
      for the frequency dependence of ac conductivity for unmodified and modified
      collagen. The behaviour observed for temperature dependencies of the exponent n
      for the three materials is considered to be related to the proton polarization
      and conduction processes.

PMID- 16099588
TI  - Vegetation associated with different walking track types in the Kosciuszko alpine
      area, Australia.
AB  - Tourism infrastructure such as walking tracks can have negative effects on
      vegetation including in mountain regions. In the alpine area around continental
      Australia's highest mountain, Mt Kosciuszko (2228 m), there is a range of walking
      tracks (paved, gravel and raised steel mesh surfaces) in addition to an extensive
      network of informal/non-hardened tracks. Vegetation characteristics were compared
      between track types on/under tracks, on the track verge, and in the adjacent
      native vegetation. For a raised steel mesh walkway there was no difference in
      vegetation under the walkway, on the verge, and 3m away. In contrast, for a non
      hardened track there was 35% bare ground on the track surface but no other
      detectable impacts. Gravel and paved tracks had distinct verges largely
      comprising bare ground and exotic species. For non-hardened tracks there was an
      estimated 270 m2 of disturbance per km of track. For wide gravel tracks the
      combined area of bare ground, exotic plants and gravel was estimated as 4290 m2
      per km, while for narrow gravel tracks it was estimated as 2940 m2 per km. For
      paved tracks there was around 2680 m2 per km of damage. In contrast, there was no
      detectable effect of raised steel mesh walkway on vegetation highlighting some of
      the benefits of this surface over other track types.

PMID- 16099589
TI  - Acute effects of insulin on beta-cells from transplantable human islets.
AB  - The functional role of autocrine insulin signaling remains unclear despite
      considerable investigation. In the present study, we tested the effects of high
      and low doses of exogenous insulin on Ca2+ signaling, insulin synthesis and
      insulin secretion in dispersed human islet cells using a combination of imaging,
      radioimmunoassay and patch-clamp electrophysiology. Although 200 nM insulin
      stimulated Ca2+ signals with larger amplitudes, the percentage of responding
      cells was lower when compared with 0.2 nM insulin. However, both 0.2 nM insulin
      and 200 nM insulin led to a transient increase in accessible cellular insulin
      content under conditions that glucose did not. This pool of insulin likely
      reflected de novo synthesis as it could be blocked by cyclohexamide or
      actinomycin D. Blocking endogenous autocrine insulin signaling in quiescent beta
      cells with the insulin receptor inhibitor HMNPA led to a reduction in insulin
      synthesis, suggesting some degree of basal activity of this positive feed-forward
      loop. Unlike exposure to high glucose, acute treatment with insulin did not
      stimulate robust insulin exocytosis, as estimated by C-peptide release and
      capacitance measurements from single beta-cells. Together these data provide
      further evidence that autocrine insulin signaling can regulate the function of
      human pancreatic beta-cells. Our findings suggest autocrine insulin signaling
      directly controls insulin protein levels, but not exocytosis, in beta-cells and
      demonstrate the functional specificity of insulin signaling and glucose signaling
      in human islet cells.

PMID- 16099590
TI  - Influence of inocula over start up of a denitrifying submerged filter applied to
      nitrate contaminated groundwater treatment.
AB  - Pure culture of denitrifying bacteria isolated from heterogeneous biofilm was
      applied as inocula to a submerged filter for removing nitrogen from contaminated
      groundwater. Five highly denitrifying bacteria were used, comparing their
      attachment, nitrogen-removal ability and final water quality in the start up of
      the system. Our experiments showed that inocula selection is the crucial step
      when the submerged filter is applied to obtain drinking water, since selected
      strains vary in their ability to colonise support material and to remove
      nitrogen, and in their effect on treated water quality during start up phase.
      Hidrogenophaga pseudoflava strain proved to be the most suitable inoculum out of
      the five tested, under the experimental conditions.

PMID- 16099592
TI  - Disease and health management in Asian aquaculture.
AB  - Asia contributes more than 90% to the world's aquaculture production. Like other
      farming systems, aquaculture is plagued with disease problems resulting from its
      intensification and commercialization. This paper describes the various factors,
      providing specific examples, which have contributed to the current disease
      problems faced by what is now the fastest growing food-producing sector globally.
      These include increased globalization of trade and markets; the intensification
      of fish-farming practices through the movement of broodstock, postlarvae, fry and
      fingerlings; the introduction of new species for aquaculture development; the
      expansion of the ornamental fish trade; the enhancement of marine and coastal
      areas through the stocking of aquatic animals raised in hatcheries; the
      unanticipated interactions between cultured and wild populations of aquatic
      animals; poor or lack of effective biosecurity measures; slow awareness on
      emerging diseases; the misunderstanding and misuse of specific pathogen free
      (SPF) stocks; climate change; other human-mediated movements of aquaculture
      commodities. Data on the socio-economic impacts of aquatic animal diseases are
      also presented, including estimates of losses in production, direct and indirect
      income and employment, market access or share of investment, and consumer
      confidence; food availability; industry failures. Examples of costs of investment
      in aquatic animal health-related activities, including national strategies,
      research, surveillance, control and other health management programmes are also
      provided. Finally, the strategies currently being implemented in the Asian region
      to deal with transboundary diseases affecting the aquaculture sector are
      highlighted. These include compliance with international codes, and development
      and implementation of regional guidelines and national aquatic animal health
      strategies; new diagnostic and therapeutic techniques and new information
      technology; new biosecurity measures including risk analysis, epidemiology,
      surveillance, reporting and planning for emergency response to epizootics;
      targeted research; institutional strengthening and manpower development
      (education, training and extension research and diagnostic services).

PMID- 16099593
TI  - In vitro platination of human breast cancer suppressor gene1 (BRCA1) by the
      anticancer drug carboplatin.
AB  - Carboplatin is an anticancer drug for the treatment of cancers affecting various
      organs including ovary and testes. It essentially exerts its cytotoxicity against
      cancerous cells via covalent attachment of platinum atom to DNA, generating
      various platinum-DNA adducts. Platinum-DNA adducts inhibit biological processes
      essential for cellular viability. However, carboplatin interacts nonspecifically
      with DNA, resulting in damaging of normal cell DNA. Potential in vitro
      interaction of carboplatin with genes encoding tumor suppressor proteins such as
      human breast cancer suppressor gene 1(BRCA1) was herein investigated. The 696--bp
      fragment of the 3'-region of BRCA1 gene (nucleotide 4897--5592) was amplified by
      RT-PCR using mRNA templates isolated from human white blood cells. Retardation of
      the electrophoretic migration on agarose gel of drug-treated DNA, in the dose
      response manner, was observed. Analysis by restriction digestion with PvuII and
      Eco O 109I suggested that the platination favorably occurred at the dGpG sequence
      of Eco O 109I-cleaved site. The semi-quantitative PCR-based assay was used to
      determine the lesion frequencies produced by carboplatin in the 696-bp fragment
      of the 3'-region of BRCA1 gene and in the 3,426-bp fragment of the BRCA1 exon 11
      of human breast adenocarcinoma MCF-7 cells. A significant decrease in DNA
      amplification was observed at 400 microM of carboplatin with approximately 1--2
      platinum atoms per BRCA1 fragment. Carboplatin caused slightly less damage at
      equimolar concentrations in cells than in cell-free BRCA1 fragment.

PMID- 16099594
TI  - Alcohol use disorder symptoms and risk-taking behavior as predictors of alcohol
      related medical events among young adults treated in emergency departments.
AB  - BACKGROUND: Studies of alcohol-positive patients in emergency departments are not
      clear on the relationship between alcohol use disorder (AUD) symptoms and risk
      for injury. METHOD: Two-hundred three young adults (118 males (58%); mean age =
      19.4 years) who were treated in two Level-1 emergency departments (ED) received
      comprehensive psychiatric interviews and completed the Alcohol Use Disorders
      Identification Test (AUDIT) and the Cognitive Appraisal of Risky Events (CARE).
      RESULTS: Males diagnosed with the AUD symptom of "drinking more or over a longer
      period than intended" are at greatest risk for requiring emergency care for an
      alcohol-related medical problem (OR = 10.8, 95% CI = 1.2,94.3, p < .04). Risk
      taking behaviors increase risk for an alcohol-related medical event for both
      genders (OR = 2.6, 95% CI=1.1,5.6.1, p < .03). Alcohol use disorder severity
      related negatively to risk for experiencing an alcohol-related medical problem
      (OR = 0.6, 95% CI = 0.4,0.9, p < .04). CONCLUSIONS: Young adults treated for
      alcohol-related medical problems often exhibit DSM-IV defined symptoms of AUD and
      are engaging in risk-taking behaviors and should be referred for an in-depth
      assessment of alcohol use disorders and risk-taking activities.

PMID- 16099595
TI  - Childhood friends who smoke: do they influence adolescents to make smoking
      transitions?
AB  - This study investigated longitudinally the extent to which childhood friends who
      smoke influence adolescents' smoking transitions, and compared that influence
      with that of parents who smoke. In a sample of 4744 children, results showed that
      the probability, per close friend, that a smoking close friend influenced the
      adolescent to make the first transition to trying smoking was 38% (95% CI: 28%,
      46%); to make the second transition from trying to monthly smoking, 10% (95% CI:
      5%, 15%); and to make the third transition from monthly to daily smoking, 11%
      (95% CI: 5%, 17%). Compared to parents' smoking, close friends' smoking was 12%
      (p=0.03) more influential for the first transition, no different for the second
      transition (p=0.53), and 16% (p=0.01) less influential for the third transition.
      Results provide new evidence suggesting that childhood close friends who smoke
      influence not only initiation but also escalation of adolescents' smoking.
      Results also confirmed the important role of parents' smoking. Targeting both
      childhood close friends' and parents' smoking would be valuable in prevention
      research.

PMID- 16099596
TI  - An observational study suggesting clinical benefit for adjuvant postoperative
      chemoradiation in a population of over 500 cases after gastric resection with D2
      nodal dissection for adenocarcinoma of the stomach.
AB  - PURPOSE: The role of adjuvant chemoradiotherapy (CRT) in D2-resected gastric
      cancer patients has not been defined yet. We investigated the effect of
      postoperative chemoradiotherapy on the relapse rate and survival rate of patients
      with D2-resected gastric cancer. METHODS AND MATERIALS: From August 1995 to April
      2001, 544 patients received postoperative CRT after curative D2 resection. During
      the same period of time, 446 patients received surgery without further adjuvant
      treatment. The adjuvant CRT consisted of 400 mg/m2 of fluorouracil plus 20 mg/m2
      of leucovorin for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks, with
      fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy.
      Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the
      completion of radiotherapy. RESULTS: The median duration of overall survival was
      significantly longer in the CRT group than in the comparison group (95.3 months
      vs. 62.6 months), which corresponds to a hazard ratio for death of 0.80 (p =
      0.0200) or a reduction of 20% in the risk of death in the CRT group. The 5-year
      survival rates were consistently longer in the CRT group at Stages II, IIIA,
      IIIB, and IV than those in the comparison group. The CRT was associated with
      increases in the median duration of relapse-free survival (75.6 months vs. 52.7
      months; hazard ratio for relapse, 0.80, p = 0.0160). CONCLUSION: Our results
      highly suggest that the postoperative chemoradiotherapy in D2-resected gastric
      cancer patients can prolong survival and decrease recurrence.

PMID- 16099597
TI  - Nuclear factor kappaB (NFkappaB) and cyclooxygenase-2 (Cox-2) expression in the
      irradiated colorectum is associated with subsequent histopathological changes.
AB  - PURPOSE: Recent studies have proposed that mucositis development is the same
      throughout the gastrointestinal tract (GIT), as it is formed from one structure
      embryologically. Radiation-induced oral mucositis studies have outlined the key
      involvement of nuclear factor kappaB (NFkappaB) and cyclooxygenase-2 (Cox-2) in
      its pathobiology. The purpose of this study was therefore to investigate the
      expression of NFkappaB and Cox-2 in the irradiated colorectum and to correlate
      these with the associated histopathologic changes. METHODS AND MATERIALS:
      Colorectal tissues from 28 colorectal cancer patients treated with preoperative
      radiotherapy were analyzed for histopathologic changes using a variety of tissue
      staining methods. The expression of NFkappaB and Cox-2 in these tissues was
      investigated using immunohistochemistry. Changes in expression of these proteins
      were then correlated with the histopathologic changes. RESULTS: Radiation therapy
      caused injury to the normal colorectal tissue surrounding tumor site,
      particularly around the blood vessels. These changes were reflected in changes in
      NFkappaB and Cox-2 expression. CONCLUSIONS: We conclude that different regions of
      the GIT, the colorectum, and oral cavity have similar underlying mechanisms of
      radiation-induced mucositis. Understanding these mechanisms will allow new
      approaches to be developed to specifically target steps in the evolution of
      alimentary mucositis.

PMID- 16099598
TI  - Long-term results of high-dose-rate brachytherapy in the primary treatment of
      medically inoperable stage I-II endometrial carcinoma.
AB  - PURPOSE: Total-abdominal hysterectomy and bilateral salpingo-oophorectomy
      (TAHBSO) is the gold-standard therapy for patients with endometrial carcinoma.
      However, patients with high operative risks are usually treated with radiation
      therapy (RT) alone. The goal of this study was to update our experience of high
      dose-rate brachytherapy (HDRB), with or without external-beam irradiation (EBRT),
      for such patients. METHODS AND MATERIALS: Between 1984 and 2003, 38 patients with
      Stage I and Stage II adenocarcinoma of the endometrium considered high operative
      risk received RT as the primary treatment. The median age was 74.1 years. Before
      1996, the local extent of the disease was assessed by an examination under
      anesthesia (EUA) and by EUA and magnetic resonance imaging (MRI) thereafter.
      Eight patients (21%) were treated with combined HDRB and EBRT, and 30 patients
      (79%) were treated with with HDRB alone. The median HDRB dose was 23.9 Gy,
      typically delivered in 3 fractions in a weekly schedule. The median EBRT dose was
      42 Gy. RESULTS: At a median follow-up of 57.5 months for patients at risk, 11
      patients (29%) have failed: 6 patients (16%) locally, 4 patients (10.5%)
      distantly, and 1 patient (3%) locally and distantly. Local failure was
      established by biopsy, and 4 patients were salvaged by TAHBSO. Higher stage and
      higher grade were both associated with increased failure rate. The 15-year
      disease-specific survival (DSS) was 78% for all stages, 90% for Stage I, and 42%
      for Stage II (p < 0.0001). The 15-year DSS was 91% for Grade I and 67% for Grade
      II and III combined (p = 0.0254). Patients with Stage I disease established by
      MRI (11 patients) and who received a total HDRB dose of 30 Gy had a DSS rate of
      100% at 10 years. Four patients experienced late toxicities: 1 Grade II and 3
      Grade III or IV. CONCLUSION: Medically inoperable Stage I endometrial carcinoma
      may be safely and effectively treated with HDRB as the primary therapy. In
      selected Stage I patients, our results are equivalent to that of surgery. We
      believe that the alternative option of HDRB as the primary therapy for selected
      Stage I endometrial carcinoma, even in patients with low operative risks, needs
      further evaluation.

PMID- 16099599
TI  - Patterns of brachytherapy practice for patients with carcinoma of the cervix
      (1996-1999): a patterns of care study.
AB  - PURPOSE/OBJECTIVE: To analyze the details of brachytherapy practice in patients
      treated for carcinoma of the cervix in the United States between 1996 and 1999.
      METHODS AND MATERIALS: Radiation facilities were selected from a stratified
      random sample. Patients were randomly selected from lists of eligible patients
      treated at each facility. A total of 442 patients' records were reviewed in 59
      facilities to obtain data about patients' characteristics, evaluation, tumor
      extent, and treatment. National estimates were made using weights that reflected
      the relative contribution of each institution and of each patient within the
      sampled institutions. From our survey we estimate that 16,375 patients were
      treated in the United States during this study period. Unless otherwise
      specified, brachytherapy practice was based on the 408 patients who had their
      brachytherapy or all their treatment at the surveyed facility. RESULTS: A total
      of 91.5% of patients underwent brachytherapy at the initial treating institution;
      8.5% were referred to a second site for brachytherapy. Forty-two percent of U.S.
      facilities referred at least some patients to a second facility for
      brachytherapy. Of U.S. facilities that treated < or =2 eligible patients per
      year, 61% referred all of their patients to a second facility for brachytherapy
      or treated with external RT alone; none of the U.S. facilities with larger
      experience (>2 eligible patients per year) referred all their patients to a
      second facility for brachytherapy treatment, but 28% referred some patients to an
      outside facility for brachytherapy. Overall, 94% of patients who completed
      treatment with curative intent received brachytherapy. Of these patients who had
      brachytherapy, 77.8%, 13.3%, and 0.9%, respectively, were treated with low-dose
      rate (LDR), high-dose-rate (HDR), or a combination of HDR and LDR brachytherapy;
      7.9% had interstitial brachytherapy (5.7% LDR and 1.9% HDR, 0.3% mixed). In
      facilities that treated >2 patients per year, 15.5% and 9.4% of brachytherapy
      procedures included HDR or interstitial, respectively; in facilities that treated
      fewer patients, 3.4% had HDR brachytherapy, and only 1.2% had interstitial
      brachytherapy. Patients treated with LDR intracavitary radiotherapy had one
      (23.5%), two (74.1%), or three (2.4%) implants. For patients treated with
      curative intent who completed radiation therapy with LDR intracavitary radiation
      therapy without hysterectomy, the median brachytherapy dose to Point A was 40.3
      Gy, and the median total dose to Point A was 82.9 Gy. Patients were treated with
      HDR intracavitary radiation therapy using a variety of treatment schedules using
      1-2 fractions (7.5%), 3-4 fractions (17.4%), 5-6 fractions (38.5%), 7-9 fractions
      (33.5%), or 12 fractions (3%). Fraction sizes were <500 cGy (29.5%), 500-<600
      (25.2%), 600 (28.1%), >600 (8%), or unknown (9.2%). For patients treated with
      HDR, the median total dose to Point A (corrected for fraction size using a
      alpha/beta = 10) was 85.8 Gy (range: 56.2-116.1 Gy). At institutions treating
      <500 new patients per year, the percentage of patients receiving a brachytherapy
      dose <40 Gy was significantly higher than at institutions treating > or =500 new
      patients per year (p < 0.0001). For LDR intracavitary radiation therapy, 5.8% had
      neither bladder nor rectal doses recorded for any of their implants, whereas in
      HDR intracavitary radiation therapy, 73.4% had neither bladder nor rectal doses
      recorded for any of their implants. The median total duration of radiation
      therapy was identical for patients who had HDR or LDR intracavitary radiation
      therapy (57 days). For LDR at institutions treating <500 new patients per year,
      the percentage of patients with treatment duration >56 days was significantly
      greater than at institutions > or =500 new patients per year (p = 0.002). Of the
      patients who had LDR intracavitary radiation therapy implants, 65% were treated
      using tandem and shielded Fletcher-Suit-Delclos colpostats; other patients had
      mini ovoids (10.9%), cylinders (3.9%), Henschke (3.7%), or other/mixed
      applicators (16.5%). In contrast, of patients treated with HDR intracavitary
      radiation therapy, 68.7% had tandem and rings, 18.2% Fletcher-Suit-Delclos
      ovoids, 7.5% mini ovoids, 2.3% cylinders, and 3.2% other or mixed applicators.
      CONCLUSIONS: The median duration of treatment and median Point A dose were very
      similar for patients treated with HDR or LDR. Patients with HDR were treated
      using a variety of treatment schedules. Different applicator types were favored
      for LDR vs. HDR. Of patients treated with HDR, 73.4% had no brachytherapy bladder
      or rectal doses recorded, suggesting that full dosimetric calculations were
      performed only for the first fraction in many institutions. Facility size
      significantly impacted on referral to another institution for brachytherapy,
      brachytherapy dose, and treatment duration.

PMID- 16099600
TI  - Prevention of acute radiation-induced proctosigmoiditis by balsalazide: a
      randomized, double-blind, placebo controlled trial in prostate cancer patients.
AB  - PURPOSE: A common complication of pelvic radiotherapy (RT) is acute radiation
      induced proctosigmoiditis (RIPS), for which a multitude of therapies have been
      tried. The 5-aminosalicylates (5-ASA), which are traditionally used to treat
      inflammatory bowel disease, have been tested; however, all but one prior
      randomized attempt to limit or prevent RIPS with 5-ASA-type agents have failed.
      We sought to evaluate balsalazide, a new 5-ASA drug, for its potential to prevent
      or limit RIPS in patients undergoing RT for carcinoma of the prostate, as a
      representative sample of pelvic RT patients. Balsalazide has a unique delivery
      system in that 99% of ingested drug is delivered to and activated in the colon, a
      higher yield than all other oral agents currently available in this class.
      Furthermore, it lacks the antigenic sulfa moiety present in sulfasalazine, the
      only other 5-ASA with demonstrated benefit in this setting. Thus, it was deemed
      an ideal candidate for preventing or limiting RIPS. METHODS AND MATERIALS:
      Eligible patients included prostate cancer patients, American Joint Committee on
      Cancer Stage T1-3, M0 being treated with external beam radiotherapy in the
      University of Kentucky Department of Radiation Medicine. Between January 1, 2003
      and July 1, 2004, 27 eligible patients were enrolled in the study. Patients were
      administered 2250 mg of balsalazide or an identical-appearing placebo twice daily
      beginning 5 days before RT and continuing for 2 weeks after completion.
      Toxicities were graded weekly according to National Cancer Institute Common
      Toxicity Criteria v. 2.0 for each of the following: proctitis, diarrhea, dysuria,
      weight loss, fatigue, nausea, and vomiting. A symptom index was formulated for
      each toxicity consisting of the toxicity's numeric grade multiplied by the number
      of days it was experienced, and summed for each grade experienced throughout the
      course of RT. RESULTS: With the exception of nausea or vomiting, seen in 3
      patients on balsalazide and 2 on placebo, all toxicities were appreciably lower
      in patients taking balsalazide. Proctitis was prevented most significantly with a
      mean proctitis index of 35.3 in balsalazide patients and 74.1 in placebo patients
      (p = 0.04). Placebo patients lost an average of 2.7 pounds, whereas balsalazide
      patients on average gained weight. Unexpectedly, dysuria was also lower in
      balsalazide-treated patients. CONCLUSIONS: Balsalazide is a new-generation 5-ASA
      drug that yields a high concentration of active drug to the distal colon. Results
      of this pilot study suggest that it is able to prevent or reduce symptoms of RIPS
      in patients undergoing RT for prostate cancer. We feel that these results justify
      the formation of a cooperative group trial to assess its efficacy in a multi
      institutional setting.

PMID- 16099601
TI  - The role of FDG PET in management of neck metastasis from head-and-neck cancer
      after definitive radiation treatment.
AB  - PURPOSE: The role of neck dissection after definitive radiation for head-and-neck
      cancer is controversial. We select patients for neck dissection based on
      postradiation therapy (post-RT), computed tomography (CT), and [18F]
      fluorodeoxyglucose positron emission tomography (FDG PET). We summarize the
      clinical outcomes of patients treated with this policy to further elucidate the
      role of FDG PET in decision making for neck dissection after primary
      radiotherapy. METHODS AND MATERIALS: Between December 1999 and February 2004, 53
      eligible patients were identified. These patients had stage N2A or higher head
      and-neck squamous cell carcinoma and had complete response of the primary tumor
      after definitive radiation with or without chemotherapy. PET or computed
      tomography (CT) scans were performed within 6 months after treatment. Neck
      dissection was performed in patients with residual lymphadenopathy (identified by
      clinical examination or CT) and a positive PET scan. Those without residual lymph
      nodes and a negative PET were observed without neck dissection. For patients with
      residual lymphadenopathy, but a negative PET scan, neck dissection was performed
      at the discretion of the attending surgeon and decision of the patient. There was
      a total of 70 heminecks available for analysis (17 patients had bilateral neck
      disease). RESULTS: There were 21 heminecks with residual lymphadenopathy
      identified on CT imaging or clinical examination and negative PET. Of these, 4
      had neck dissection and were pathologically negative. The remaining 17 were
      observed without neck dissection. There was a total of 42 heminecks without
      residual lymph nodes on post-RT CT imaging or clinical examination with a
      negative PET. They were also observed without neck dissection. Seven heminecks
      had a positive PET scan and residual lymphadenopathy. Six of them had neck
      dissection and 1 had fine-needle aspiration of a residual node; 3 contained
      residual viable cancer and 4 were pathologically negative. At median follow up of
      26 months (range, 12-57 months), no regional failure was identified. The negative
      predictive value of PET was 100% and positive predictive value was 43%.
      CONCLUSION: For patients who have no evidence of residual lymphadenopathy and a
      negative FDG PET scan 12 weeks after definitive radiation, neck dissection can be
      safely withheld. Even in cases in which small residual lymphadenopathy was
      observed, regional recurrences have not occurred when the post-RT PET scan was
      negative and neck dissection was withheld. For patients with large residual
      lymphadenopathy (greater than 2.0-3.0 cm in size) but a negative post-RT FDG PET,
      further studies with longer follow-up are necessary to determine the
      appropriateness of withholding neck dissection.

PMID- 16099602
TI  - Increased expression of nitric oxide synthase and cyclooxygenase-2 is associated
      with poor survival in cervical cancer treated with radiotherapy.
AB  - PURPOSE: To investigate the expression of inducible nitric oxide synthase (iNOS)
      and cyclooxygenase-2 (COX-2) in cervical cancer and their association with
      clinical outcome in patients treated with radical radiotherapy. METHODS AND
      MATERIALS: One hundred sixty-seven consecutive patients with FIGO Stages IB-IVA
      squamous cell cervical cancer underwent radical radiotherapy, including external
      beam radiotherapy or high-dose-rate brachytherapy, or both, between 1989 and
      2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded
      tissues were performed. Univariate and multivariate analyses were performed to
      identify and evaluate the effects of the factors affecting patient survival.
      RESULTS: Positive immunostainings of iNOS and COX-2 were observed in 58.7% and
      64.1% of the participants, respectively. The expression of both iNOS and COX-2
      was positively correlated (Spearman correlation coefficient = 0.49, p < 0.01),
      and their overexpression provided independent predictors of distant metastasis
      (odds ratio = 5.22 and 10.07, respectively; p < 0.01 for all). iNOS- and COX-2
      expressing patients had significantly shorter disease-free survival (p < 0.01,
      both) and cause-specific overall survival (p = 0.01, p < 0.01, respectively).
      Patients with iNOS-positive/COX-2-positive tumors had the poorest survival rates.
      Coexpression of iNOS/COX-2, together with bulky tumor and advanced stage were
      independent prognostic factors for disease-free survival. CONCLUSION:
      Overexpression of iNOS or COX-2 or both was associated with decreased survival
      and a greater propensity to metastasize in cervical cancer patients treated with
      radiotherapy. Coexpression of iNOS and COX-2 may represent a useful biologic
      marker in patients receiving radical radiotherapy for cervical cancer.

PMID- 16099603
TI  - The Rhizobium etli bioMNY operon is involved in biotin transport.
AB  - Because Rhizobium etli CE3 is normally dependent on an external source of biotin
      and lacks orthodox biotin biosynthesis genes, we undertook an analysis of biotin
      uptake in this organism. By complementation of a Sinorhizobium meliloti bioM
      mutant we isolated an R. etli chromosomal region encoding homologs of the S.
      meliloti bioMNB genes, whose products have been implicated in intracellular
      biotin retention in that organism. Disruption of the R. etli bioM resulted in a
      mutant which took up biotin at a lower rate and accumulated significantly less
      biotin than the wild type. As in S. meliloti, the R. etli bioMN gene-products
      resemble the ATPase and permease components, respectively, of an ABC-type
      transporter. The bioB gene product is in fact similar to members of the BioY
      family, which has been postulated to function in biotin transport, and we refer
      to this gene as bioY. An R. etli bioY mutant exhibited lower biotin uptake than
      the wild-type, providing the first experimental evidence for a role of BioY in
      biotin transport. We show that the bioMNY operon is transcriptionally repressed
      by biotin. An analysis of the competitiveness of the wild-type strain versus the
      bioM mutant showed that the mutant had a diminished capacity to form nodules on
      bean plants.

PMID- 16099604
TI  - Modulation of plant ethylene levels by the bacterial enzyme ACC deaminase.
AB  - Soil microorganisms that produce the enzyme 1-aminocyclopropane-1-carboxylate
      (ACC) deaminase promote plant growth by sequestering and cleaving plant-produced
      ACC, and thereby lowering the level of ethylene in the plant. Decreased ethylene
      levels allows the plant to be more resistant to a wide variety of environmental
      stresses. Here, the biochemistry of ACC deaminase; the environmental
      distribution, regulation, evolution and expression of ACC deaminase genes; and
      information regarding the effect of this enzyme on different plants is documented
      and discussed.

PMID- 16099605
TI  - Comparative genome analysis of Bacillus cereus group genomes with Bacillus
      subtilis.
AB  - Genome features of the Bacillus cereus group genomes (representative strains of
      Bacillus cereus, Bacillus anthracis and Bacillus thuringiensis sub spp.
      israelensis) were analyzed and compared with the Bacillus subtilis genome. A core
      set of 1381 protein families among the four Bacillus genomes, with an additional
      set of 933 families common to the B. cereus group, was identified. Differences in
      signal transduction pathways, membrane transporters, cell surface structures,
      cell wall, and S-layer proteins suggesting differences in their phenotype were
      identified. The B. cereus group has signal transduction systems including a
      tyrosine kinase related to two-component system histidine kinases from B.
      subtilis. A model for regulation of the stress responsive sigma factor sigmaB in
      the B. cereus group different from the well studied regulation in B. subtilis has
      been proposed. Despite a high degree of chromosomal synteny among these genomes,
      significant differences in cell wall and spore coat proteins that contribute to
      the survival and adaptation in specific hosts has been identified.

PMID- 16099606
TI  - Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus
      survive gastrointestinal transit of healthy volunteers consuming yogurt.
AB  - To date, there is significant controversy as to the survival of yogurt bacteria
      (namely, Streptococcus thermophilus and Lactobacillus delbrueckii subsp.
      bulgaricus) after passage through the human gastrointestinal tract. Survival of
      both bacterial species in human feces was investigated by culture on selective
      media. Out of 39 samples recovered from 13 healthy subjects over a 12-day period
      of fresh yogurt intake, 32 and 37 samples contained viable S. thermophilus
      (median value of 6.3 x 10(4) CFU g(-1) of feces) and L. delbrueckii (median value
      of 7.2 x 10(4)CFU g(-1) of feces), respectively. The results of the present study
      indicate that substantial numbers of yogurt bacteria can survive human
      gastrointestinal transit.

PMID- 16099607
TI  - Regulation of an insect cytochrome P450 monooxygenase gene (CYP6B1) by aryl
      hydrocarbon and xanthotoxin response cascades.
AB  - Many organisms respond to toxic compounds in their environment by inducing
      regulatory networks controlling the expression and activity of cytochrome P450
      monooxygenase (P450s) detoxificative enzymes. In particular, black swallowtail
      (Papilio polyxenes) caterpillars respond to xanthotoxin, a toxic phytochemical in
      their hostplants, by activating transcription of the CYP6B1 promoter via several
      regions located within 150 nt of the transcription initiation site. One such
      element is the xenobiotic response element to xanthotoxin (XRE-Xan) that lies
      upstream of consensus XRE-AhR (xenobiotic response element to the aryl
      hydrocarbon receptor) and OCT-1 (octamer-1 binding site) element known to be
      utilized in mammalian aryl hydrocarbon response cascades. Two-plasmid
      transfections conducted in Sf9 cells have indicated that XRE-Xan, XRE-AhR and a
      number of other proximal elements, but not OCT-1, are critical for basal as well
      as xanthotoxin- and benzo[alpha]pyrene-induced transcription of the CYP6B1
      promoter. Four-plasmid transfections with vectors co-expressing the spineless
      (Ss) and tango (Tgo) proteins, the Drosophila melanogaster homologues of
      mammalian AhR and ARNT, have indicated that these proteins enhance basal
      expression of the CYP6B1 promoter but not the magnitude of its xanthotoxin and
      benzo[alpha]pyrene induction. Based on these results, we propose that these
      Drosophila transcription factors modulate basal expression of this promoter in a
      ligand-independent manner and attenuate its subsequent responses to planar aryl
      hydrocarbons (benzo[alpha]pyrene) and allelochemicals (xanthotoxin).

PMID- 16099608
TI  - Functional complementation of yeast ribosomal P0 protein with Plasmodium
      falciparum P0.
AB  - A complex of three phosphoproteins (P0, P1 and P2) constitutes the stalk region
      at the GTPase center of the eukaryotic large ribosomal subunit, amongst which the
      protein P0 plays the most crucial role. Earlier studies have shown the functional
      complementation of the conditional P0-null mutant of Saccharomyces cerevisiae
      (W303dGP0) with orthologous P0 genes from fungal and mammalian organisms, but not
      the protozoan parasite Leishmania infantum. In this paper we show that the PfP0
      gene from the protozoan malaria parasite Plasmodium falciparum can functionally
      complement the conditional P0-null W303dGP0 mutant of S. cerevisiae. Unlike the
      above orthologous genes, PfP0 gene could also rescue the D67dGP0 strain, which in
      addition to being a conditional null for ScP0 gene, is a null-mutant for both
      ScP1alpha and beta genes. However, under stress conditions such as high
      temperature, salt and osmolarity, PfP0 gene could not rescue D67dGP0 strain.
      Ribosomes purified from W303dGP0 carrying PfP0 gene did not contain ScP1 protein,
      indicating a lack of binding of ScP1 to PfP0 protein. Yeast 2-hybrid analysis
      further confirmed the lack of binding of ScP1 to PfP0 protein. The polymerizing
      activities of ribosomes with ScP0 or PfP0 protein, in the absence of ScP1
      protein, were found to be about 40-45% that of ribosomes with all the yeast P
      proteins. In its sensitivity to the inhibitor sordarin, PfP0 was similar to the
      P0 protein from the fungus Aspergillus fumigatus. These results indicate a closer
      functional relationship of P. falciparum P0 gene to fungal P0 genes.

PMID- 16099609
TI  - Amides as cryoprotectants for freezing stallion semen: a review.
AB  - Stallion semen cryopreservation, despite its impact on the horse industry, is not
      an established technology. During the last years, a number of modifications have
      been proposed to the freezing process, however, a large population of stallions
      still have poor semen quality and fertility after frozen-thawed. Glycerol
      toxicity could be a reason for the variation on stallion sperm freezability.
      There are limited publications concerning the use of alternative cryoprotectants
      for equine sperm. Glycerol is contraceptive for some species and other
      cryoprotectors, such as amides, have been show to be a good option for freezing
      semen of these species. Recent reports have shown encouraging data respecting the
      use of amides as cryoprotectants for stallions, with more remarkable improvements
      for semen from stallions that freeze poorly when glycerol is used.

PMID- 16099610
TI  - Correlation of laboratory and production freeze drying cycles.
AB  - The purpose of this study was to develop the correlation of cycle parameters
      between a laboratory and a production freeze-dryer. With the established
      correlation, key cycle parameters obtained using a laboratory dryer may be
      converted to those for a production dryer with minimal experimental efforts. In
      order to develop the correlation, it was important to consider the contributions
      from the following freeze-drying components: (1) the dryer, (2) the vial, and (3)
      the formulation. The critical parameters for the dryer are the shelf heat
      transfer coefficient and shelf surface radiation emissivity. The critical
      parameters for the vial are the vial bottom heat transfer coefficients (the
      contact parameter Kcs and separation distance lv), and vial top heat transfer
      coefficient. The critical parameter of the formulation is the dry layer mass
      transfer coefficient. The above heat and mass transfer coefficients were
      determined by freeze-drying experiments in conjunction with mathematical
      modeling. With the obtained heat and mass transfer coefficients, the maximum
      product temperature, Tbmax, during primary drying was simulated using a primary
      drying subroutine as a function of the shelf temperature and chamber pressure.
      The required shelf temperature and chamber pressure, in order to perform a
      successful cycle run without product collapse, were then simulated based on the
      resulting values of Tbmax. The established correlation approach was demonstrated
      by the primary drying of the model formulation 5% mannitol solution. The cycle
      runs were performed using a LyoStar dryer as the laboratory dryer and a BOC
      Edwards dryer as the production dryer. The determined normalized dried layer mass
      transfer resistance for 5% mannitol is expressed as RpN=0.7313+17.19l, where l is
      the receding dry layer thickness. After demonstrating the correlation approach
      using the model formulation 5% mannitol, a practical comparison study was
      performed for the actual product, the lactate dehydrogenase (LDH) formulation.
      The determined normalized dried layer mass transfer resistance for the LDH
      formulation is expressed as RpN=4.344+10.85l. The operational templates Tbmax and
      primary drying time were also generated by simulation. The cycle run for the LDH
      formulation using the Edwards production dryer verified that the cycle developed
      in a laboratory freeze-dryer was transferable at the production scale.

PMID- 16099611
TI  - The effect of internal structure of selected water-Tween 40-Imwitor 308-IPM
      microemulsions on ketoprofene release.
AB  - Microemulsions are a promising vehicle for administrating drugs. In order to lay
      the basis for predicting drug release under in vivo conditions, where the
      microemulsion composition is continuously varying, we have studied the release of
      ketoprofene as a model drug, from microemulsions on a dilution line containing,
      initially, 20 wt.% of isopropyl miristate (IPM) and 80 wt.% of the surfactant
      (Tween 40/co-surfactant (Imwitor 308, 1:1 wt.% mixture. Mixture compositions
      corresponding to the different types and structure of microemulsion were
      identified by measuring density, surface tension, electric conductivity, pH and
      differential scanning calorimetry. Ketoprofene release was then measured for each
      type and structure. The main factor influencing ketoprofene release was shown to
      be the strength of the interactions between microemulsion components. Strong
      interactions prevented rapid ketoprofene release in the water-in oil region,
      although the release was not dependent on the degree of percolation. Release
      kinetics in all cases follow zero order kinetics, indicating that the release
      rate is dependent on the diffusion of ketoprofene inside the microemulsion
      carrier. Combining different methods to obtain the physical and structural
      properties of microemulsions can be thus used to predict the release of
      ketoprofen from a microemulsion.

PMID- 16099612
TI  - Herb-drug interaction of Evodia rutaecarpa extract on the pharmacokinetics of
      theophylline in rats.
AB  - The extract of Evodia rutaecarpa fruit and its preparation were used for the
      treatment of gastrointestinal disorders and headache. To assess the possible herb
      drug interaction, the ethanol extract of Evodia rutaecarpa fruit (1 and 2
      g/kg/day, p.o.) and the herbal preparation Wu-Chu-Yu-Tang (1 and 5 g/kg/day) were
      given to rats daily for three consecutive days and on the fourth day theophylline
      was administered (2 mg/kg, i.v.). Theophylline concentration in blood was
      measured by a microdialysis coupled to a liquid chromatographic system.
      Pharmacokinetic data were calculated by noncompartmental model. The results
      indicate that the theophylline level was significantly decreased by the
      pretreatment with the extract of Evodia rutaecarpa and herbal preparation Wu-Chu
      Yu-Tang with dose-related manner. It is suggested that the herb-drug interaction
      may occur through the induction of the metabolism of theophylline.

PMID- 16099613
TI  - Hypoglycaemic effect of Triticum repens P. Beauv. in normal and diabetic rats.
AB  - The hypoglycaemic effect of an aqueous extract of Triticum repens (TR) rhizomes
      was investigated in normal and streptozotocin (STZ) diabetic rats. After a single
      oral administration of the aqueous extract (20mg/kg) a significant decrease on
      blood glucose levels in STZ diabetic rats (p<0.001) was observed; the blood
      glucose levels were normalized after 2 weeks of daily oral administration of TR
      aqueous extract (20mg/kg) (p<0.001). Significant reduction on blood glucose
      levels were noticed in normal rats after both acute (p<0.001) and chronic
      treatment (p<0.001). In addition, no changes were observed in basal plasma
      insulin concentrations after treatment in either normal or STZ diabetic rats
      indicating that the underlying mechanism of this pharmacological activity seems
      to be independent of insulin secretion. We conclude that the aqueous extract of
      TR exhibits a potent hypoglycaemic activity in STZ rats without affecting basal
      plasma insulin concentrations.

PMID- 16099614
TI  - The in vitro pharmacological activities and a chemical investigation of three
      South African Salvia species.
AB  - Salvia species (sage) are well known in folk medicine throughout the world. In
      South Africa sage is used against fever and digestive disorders. Three closely
      related South African species (Salvia stenophylla, Salvia repens and Salvia
      runcinata) were investigated for their anti-oxidant (DPPH assay); anti
      inflammatory (5-lipoxygenase and cyclo-oxygenase assays); antimalarial (tritiated
      hypoxanthine incorporation assay); antimicrobial (disc diffusion and micro
      dilution assays) properties and toxicity profile (tetrazolium-based assay). The
      solvent extracts exhibited anti-oxidant, antimalarial and antibacterial and poor
      anti-inflammatory properties. The essential oils exhibited anti-inflammatory and
      antimalarial properties, but displayed poor anti-oxidant and antimicrobial
      activity. The extract of Salviastenophylla and the essential oil of Salvia
      runcinata displayed the highest toxicity profile. Overall, Salvia runcinata
      displayed the most favorable activity of all three taxa tested with an IC(50)
      value of 6.09 (anti-oxidant); 29.05 (antimalarial) and 22.82 microg/ml (anti
      inflammatory). Analytical procedures (GC-MS and HPLC-UV) were employed to
      generate chromatographic profiles for the essential oils and solvent extracts
      respectively. The HPLC analysis revealed the presence of rosmarinic acid in all
      three taxa while carnosic acid was only present in Salvia repens and Salvia
      stenophylla. The GC-MS analysis showed that oils were qualitatively and
      quantitatively variable. beta-Caryophyllene was present in large amounts in all
      three taxa. Other components present include camphor, alpha-pinene and alpha
      bisabolol. The results of the in vitro pharmacological activities provide a
      scientific basis to validate the use of these Salvia species in traditional
      medicine in South Africa.

PMID- 16099615
TI  - The contribution of forensic science to crime analysis and investigation:
      forensic intelligence.
AB  - The debate in forensic science concentrates on issues such as standardisation,
      accreditation and de-contextualisation, in a legal and economical context, in
      order to ensure the scientific objectivity and efficiency that must guide the
      process of collecting, analysing, interpreting and reporting forensic evidence.
      At the same time, it is recognised that forensic case data is still poorly
      integrated into the investigation and the crime analysis process, despite
      evidence of its great potential in various situations and studies. A change of
      attitude is needed in order to accept an extended role for forensic science that
      goes beyond the production of evidence for the court. To stimulate and guide this
      development, a long-term intensive modelling activity of the investigative and
      crime analysis process that crosses the boundaries of different disciplines has
      been initiated. A framework that fully integrates forensic case data shows
      through examples the capital accumulated that may be put to use systematically.

PMID- 16099616
TI  - Tensile properties of the human acetabular labrum-the first report.
AB  - The tensile properties of the human acetabular labrum were investigated using a
      uniaxial tension testing apparatus. The superior quadrant of the acetabular
      labrum was harvested from patients who underwent hip surgery. The obtained labra
      were sliced and shaped into rectangles for measuring uniaxial tension. We
      hypothesized that several characteristics such as gender, age, degeneration due
      to primary ailment, and the severity of the acetabular dysplasia would influence
      the tensile properties of the labrum. Antero-posterior radiographs of the pelvis
      have been used to evaluate the severity of the acetabular dysplasia and to
      diagnose the developmental dysplasia of the hip joint (DDH) clinically. Thus, we
      investigated the correlation between each of two representative radiological
      measurements-the CE angle and the Sharp angle-and tensile properties to assess
      the influence of the severity of the acetabular dysplasia. The tensile stress
      strain curves for the labrum assumed a sigmoid shape. The mean tensile stress at
      failure for all specimens was 8.8+/-4.1 MPa. The mean strain at failure for all
      specimens was 48.5+/-10.4%. The mean tensile modulus was 66.4+/-42.2 MPa. Mean
      tensile stress at failure for specimens from males was greater than that of
      specimens from females. A significant difference was found in the maximum stress
      at failure among the three diagnosis-based groups: the other group withstood the
      highest stress before failure, whereas the osteoarthritis (OA) group withstood
      the lowest. No significant correlations with age or radiological characteristics
      were found for tensile stress, strain at failure, or tensile modulus. Our results
      suggest that labra obtained from male patients have stronger tensile stress than
      those from female patients, and that degenerative changes may influence the
      properties of the acetabular labrum.

PMID- 16099617
TI  - Pancreatic panniculitis.

PMID- 16099618
TI  - TNF dose reduction in isolated limb perfusion.
AB  - AIMS: Isolated limb perfusion with TNF and melphalan (TM-ILP) is highly effective
      in the local treatment of advanced sarcoma and melanoma of the limb. The optimal
      dose of TNF for this procedure is not well established. The aim of this study was
      to assess the efficacy and toxicity of TM-ILPs with reduced TNF dose. METHOD:
      Largest single institution prospective database on TNF-based ILP. Out of 339 TM
      ILPs performed between 1991 and 2003, 64 procedures were performed with reduced
      TNF dose (<3 mg in arm perfusions, <4 mg in leg perfusions). Response rates and
      toxicity of the procedure and outcome of the patients are evaluated. RESULTS:
      Complete response in melanoma patients after reduced-dose ILP was 75 vs 69% after
      standard-dose ILPs (overall response 94 vs 95%, respectively); overall response
      in non-melanoma patients was 69 (reduced) vs 74% (standard). Response rates and
      outcome were comparable with the procedures performed with standard-dose TNF
      (p=NS for response, local/systemic progression and survival after multivariate
      analysis, both in melanoma and in non-melanoma patients). Systemic and local
      toxicity did not differ statistically between reduced- and standard dose TM-ILPs.
      CONCLUSION: Provided doses at 1mg or higher are used, TM-ILP with TNF dose
      reduction for both melanoma and non-melanoma patients seems to be as effective as
      the standard dose procedure in terms of response rate and patient outcome.
      Numbers to formally confirm or reject this hypothesis are too large for such a
      non-inferiority trial to be conducted in patients with these rare conditions.

PMID- 16099619
TI  - Behavioral effects of toluene in rats selectively bred for infantile vocalization
      rate.
AB  - Glue sniffing is epidemic among children living in poverty in Latin America.
      Previous research has shown that abused inhalants such as toluene share
      pharmacological properties with anxiolytic drugs, and that personality factors
      such as degree of anxiety have been proposed to modulate the effects of these
      drugs. To study this interaction in an animal model, rats selectively bred for
      high (High) or low (Low) rates of distress calls after maternal separation
      (ultrasonic vocalizations, USVs) were used to investigate toluene's acute and
      long-term effects on two measures of anxiety behavior. At ten days of age,
      neonatal subjects were administered toluene (1 g/kg i.p.) and USVs were recorded.
      The subjects were retested as juveniles on an elevated plus maze to examine
      sequela of earlier toluene exposure. Acute toluene administration reduced USVs
      relative to control groups in neonates of both lines, indicating anxiolysis. As
      expected, Lows had reduced USVs relative to Highs. At 28 days of age, Highs spent
      more time in the open arms of the elevated plus maze than Lows. However, prior
      neonatal toluene exposure blocked this reversal of behavioral phenotype. This
      suggests that early toluene exposure compromised a compensatory process occurring
      during this developmental period, which may have been maternally mediated. These
      results have implications for the effects of early drug exposure on plasticity in
      the developing nervous system.

PMID- 16099620
TI  - Changes in sleep-wake cycle after chronic exposure to uranium in rats.
AB  - Uranium is a heavy metal known to induce toxicity in kidneys. It is also known to
      enter the central nervous system, thus inducing neurophysiological effects, after
      exposure to relatively high concentrations. The effect of chronic uranium
      exposure (40 mg l(-1) in drinking water, for 90 days) on electroencephalographic
      architecture has been studied on freely moving rats using a telemetry technique.
      The main effects of uranium on the sleep-wake cycle were an increase in rapid eye
      movement sleep (REM-sleep) and theta band power during the light period, as early
      as Day 30 after exposure commenced. The most probable explanation for these
      effects is that uranium directly affects the brain. This increase in REM-sleep
      was previously described in human depression or models of chronically stressed
      rats and it may be assimilated with some protective or compensatory mechanisms.

PMID- 16099621
TI  - Rats exposed to Solanum lycocarpum fruit in utero and during lactation:
      neurochemical, behavioral and histopathological effects.
AB  - Solanum lycocarpum St. Hil (Solanaceae) is a native shrub very common in the
      Brazilian savannah. This plant contains steroidal glycoalkaloids that can be
      transformed into an intermediate for steroidal drug production. In this way, it
      is very possible that these glycoalkaloids and its aglycone, once in the body by
      ingestion of S. lycocarpum fruits, may act by disrupting the endocrine system.
      Because its fruits may be consumed by pregnant animals in the fields, the present
      study determined the possible toxic effects of exposure to S. lycocarpum fruit
      (10% added in the diet) from gestation day (GD) 6 to postnatal day (PND) 07 in
      rat dams. The unripe fruits contained 0.6% of solamargine and 0.9% of solasonine.
      S. lycocarpum, 10% in the diet, during gestation and the beginning of lactation
      reduced intrauterine growth. In addition, 20% of the treated dams showed some
      dead pups at birth. Reduced body weight was observed from birth through adulthood
      in male and female offspring exposed to 10% S. lycocarpum unripe fruits. During
      adulthood, female offspring showed impaired sexual behavior and male offspring
      showed prominent degeneration of testis germinative cells, characterized by a
      reduced number of germ cells and vacuolation. Also, the exposed offspring showed
      reduced hypothalamic norepinephrine (NOR), vanillylmandelic acid (VMA), 3-methoxy
      4-hydrophenylglycol (MHPG) and homovanillic acid (HVA) levels, and reduced
      striatum NOR, HVA, VMA, MHPG, dopamine (DA), dihydroxyphenylacetic acid (DOPAC)
      and 5-hydroxyindolacetic acid (5-HIAA) levels. These results suggest that the
      fruit may act as an estrogen, with a long-term effect, impairing the receptive
      lordosis behavior of female offspring and promoting testis abnormalities in male
      offspring at adulthood. Finally, it appears to disrupt brain organization since
      important central monoamine level alterations were also observed.

PMID- 16099622
TI  - The occurrence of rare rpoB mutations in rifampicin-resistant clinical
      Mycobacterium tuberculosis isolates from Kuwait.
AB  - Mutations associated with rifampicin (RIF) resistance in two regions of the rpoB
      gene were studied by line probe (INNO-LiPA Rif. TB) assay (LiPA) and/or DNA
      sequencing in 32 RIF-resistant and 21 RIF-susceptible Mycobacterium tuberculosis
      strains isolated from 53 tuberculosis patients in Kuwait. The LiPA identified all
      susceptible strains as RIF sensitive, and the DNA sequences of the 81bp
      rifampicin resistance-determining region (RRDR) and the N-terminal region of the
      rpoB gene from five isolates were identical to the wild-type sequences from M.
      tuberculosis H(37)Rv. The LiPA identified 24 of 32 (75%) phenotypically
      documented RIF-resistant M. tuberculosis isolates as RIF resistant, with specific
      detection of mutation in 19 isolates, whilst 8 strains were identified as RIF
      susceptible. DNA sequencing of the RRDR confirmed the results for the 19 RIF
      resistant isolates and identified precise mutations in five isolates for which
      specific base changes could not be determined by LiPA, as well as identifying a
      mutation (insertion 514TTC) in three isolates and no mutation in five of the
      eight isolates that were detected as RIF susceptible by LiPA. Two of the latter
      five isolates contained a V146F mutation in the N-terminal region of the rpoB
      gene and were recovered from patients of Middle Eastern origin. These analyses
      identified 11 different mutations in two regions of the rpoB gene. The majority
      of the isolates carrying identical or no mutations in the rpoB gene exhibited
      unique DNA banding patterns in fingerprinting studies. The occurrence of rare
      mutations in the rpoB gene, namely insertion 514TTC in 3 (9%) and V146F in 2 (6%)
      of 32 RIF-resistant M. tuberculosis isolates from Kuwait, is the highest reported
      so far.

PMID- 16099623
TI  - Induction of pro-inflammatory cytokine release by human macrophages during
      exposure of Streptococcus pneumoniae to penicillin is influenced by minimum
      inhibitory concentration ratio.
AB  - beta-Lactam antibiotics cause release of pro-inflammatory bacterial cell wall
      structures. We determined the effect of penicillin treatment of Streptococcus
      pneumoniae on the induction of tumour necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) genes by human macrophages and the influence of
      antibiotic concentration and bacterial growth phase upon this induction. Gene
      expression was measured by real-time polymerase chain reaction (PCR) and protein
      was measured by enzyme-linked immunosorbent assay (ELISA). Treatment of lag phase
      S. pneumoniae with one-eighth minimum inhibitory concentration (MIC) penicillin
      resulted in enhanced expression of TNF-alpha messenger RNA (mRNA), but not TNF
      alpha protein at 6h compared with untreated bacteria. IL-1beta mRNA and protein
      were not affected by these bacteria. MIC treatment of lag or early log phase
      bacteria induced both protein and mRNA for IL-1beta. Bacteria exposed to
      concentrations of penicillin that cause lysis (MIC) or no lysis with
      morphological changes (sub-MIC) induce differential patterns of pro-inflammatory
      cytokine expression by human macrophages.

PMID- 16099624
TI  - Rifampicin+ceftriaxone versus vancomycin+ceftriaxone in the treatment of
      penicillin- and cephalosporin-resistant pneumococcal meningitis in an
      experimental rabbit model.
AB  - This study was planned to compare the efficacy of ceftriaxone+vancomycin with
      ceftriaxone+rifampicin in a rabbit model of penicillin and cephalosporin
      resistant Streptococcus pneumoniae meningitis. Meningitis was induced by
      intracisternal inoculation of S. pneumoniae. After 18 h of incubation, Group 1
      was given saline solution (control group), whilst Groups 2 and 3 were given
      ceftriaxone+vancomycin and ceftriaxone+rifampicin, respectively. Cerebrospinal
      fluid bacterial concentrations were measured at 0, 2, 12, 14 and 24 h after
      therapy was initiated. In the control group, bacterial growth was present at all
      time points, whereas no growth was observed in either the ceftriaxone+vancomycin
      group or the ceftriaxone+rifampicin group after 2 h of therapy.
      Ceftriaxone+rifampicin was found to be as effective as ceftriaxone+vancomycin in
      the treatment of penicillin-resistant S. pneumoniae meningitis in experimental
      rabbit model.

PMID- 16099625
TI  - Investigation of erythromycin and tetracycline resistance genes in methicillin
      resistant staphylococci.
AB  - In this study, erythromycin [erm(A) and erm(C)] and tetracycline [tet(K) and
      tet(M)] resistance genes were investigated by multiplex polymerase chain reaction
      (PCR) in a total of 56 methicillin-resistant (mecA+) staphylococcal hospital
      isolates, 28 of which were determined to be Staphylococcus aureus (MRSA) and the
      other 28 were coagulase-negative staphylococci (MRCNS). Internal control primers
      amplifying a specific fragment of 16S rDNA of staphylococci were included in the
      multiplex PCR protocol to ensure the efficacy of amplification and to determine
      any PCR inhibition. No resistance genes were detected in 5 of 56 (8.9%) isolates
      in the study. In the study, tet(K) genes were detected widely (42.9%) in MRCNS,
      whilst tet(M) genes were detected in MRSA (50.0%). Regarding the erythromycin
      resistance genes, whilst erm(A) genes were detected in most (71.4%) MRSA
      isolates, detection rates of erm(C) genes were the same (64.3%) both in MRCNS and
      MRSA. The resistance rates for tetracycline and erythromycin were 57.1% and
      78.6%, respectively, in MRSA isolates. In conclusion, in this study, the
      multiplex PCR technique including an internal control is shown to be a fast,
      sensitive, reliable, practical, reproducible and economic technique for the
      detection of erythromycin and tetracycline resistance in staphylococcal isolates.

PMID- 16099626
TI  - Absence of the plasmid-mediated quinolone resistance qnrA gene among
      Campylobacter jejuni clinical isolates from Greece.

PMID- 16099627
TI  - Chain dynamics in a chiral C phase by deuteron spin relaxation study.
AB  - Molecular reorientations and internal conformational transitions of an aligned
      chiral liquid crystal (LC) 10B1M7 are studied by means of deuterium spin-lattice
      relaxation in its smectic A (SmA) and smectic C* (SmC*) phase. The motional model
      which is applicable to uniaxial phases of many LCs is found to be adequate even
      when the phase is a tilted SmC* phase. The deuterium NMR spectrum in this phase
      cannot discern rotations of the molecular director about the pitch axis. The
      basic assumption is that the phase biaxiality is practically unobservable.
      However, the relaxation rates can be accounted for by the tilt angle between the
      molecular director and the layer normal in the SmC* phase. The tumbling motion
      appears to show a higher activation energy upon entering from the uniaxial SmA
      into the SmC* phase.

PMID- 16099628
TI  - Visuo-verbal interactions in working memory: evidence from event-related
      potentials.
AB  - Working memory is thought to involve separate modality-specific storage systems.
      Interactions between these storage systems were investigated using a novel cross
      modal 2-back paradigm. 2-back, 1-back and target items were presented either
      visually as a verbalizable linedrawing or auditorily as a digitized spoken word.
      ERPs for auditory targets were primarily modulated by the presentation modality
      of the 2-back item, whereas ERPs for visual targets were largely modulated by
      presentation modality of the 1-back item. Results indicate that verbalizable
      pictures are only partially transformed into a phonological code for rehearsal in
      working memory. Furthermore, results support the idea of a more stable and
      persistent auditory short-term store as opposed to a more transiently activated
      visual store for verbalizable material.

PMID- 16099629
TI  - Novel therapies for rheumatoid arthritis.
AB  - Recent years have witnessed significant advancements in the therapeutic approach
      to rheumatoid arthritis. The introduction of biologic agents, in particular
      inhibitors of tumor necrosis factor (TNF), has ushered a new era in which the
      goal of therapy has become achieving very low levels of disease activity. Success
      achieved with the TNF inhibitors has reinvigorated research into targeting other
      componenets of the dysregulated immune system in RA. A number of approaches,
      targeting various cytokines, other inflammatory mediators, and populations of
      immunocompetent cells, seem promising.

PMID- 16099630
TI  - Low fat dietary intervention with omega-3 fatty acid supplementation in multiple
      sclerosis patients.
AB  - OBJECTIVES: To determine whether a low fat diet supplemented with omega-3
      positively affects quality of life (QOL) in relapsing-remitting MS (RRMS)
      patients. In this 1-year long double-blind, randomized trial, patients were
      randomized to two dietary interventions: the "Fish Oil" (FO) group received a low
      fat diet (15% fat) with omega-3 FOs and the "Olive Oil" (OO) group received the
      AHA Step I diet (fat 30%) with OO supplements. The primary outcome measure was
      the Physical Components Summary Scale (PCS) of the Short Health Status
      Questionnaire (SF-36). Additional measures using MS specific QOL questionnaires,
      neurological status and relapse rate were obtained. RESULTS: 31 RRMS patients
      were enrolled, with mean follow up over 11 +/- SD 2.9 months. Clinical benefits
      favoring the FO group were observed on PCS/SF-36 (P = 0.050) and MHI (P = 0.050)
      at 6 months. Reduced fatigue was seen on the OO diet at 6 months (P = 0.035). The
      relapse rate decreased in both groups relative to the rates during the 1 year
      preceding the study: mean change in relapse rate in the FO group: -0.79 +/- SD
      1.12 relapses/year (P = 0.021) vs. -0.69 +/- SD 1.11 (P = 0.044) in the OO group.
      This study suggests that a low fat diet supplemented with omega-3 PUFA can have
      moderate benefits in RRMS patients on concurrent disease modifying therapies.

PMID- 16099631
TI  - Effects of fenofibrate and insulin on the biosynthesis of unsaturated fatty acids
      in streptozotocin diabetic rats.
AB  - Both insulin and PPAR-alpha up-modulate hepatic Delta9, Delta6 and Delta5
      desaturating enzymes involved in the biosynthesis of mono- and polyunsaturated
      fatty acids. Currently, we have examined for 9 days the independent and
      simultaneous effects of daily glargine insulin and fenofibrate administration on
      the insulinemia, glycemia, hepatic acyl-CoA oxidase activity and mRNAs and
      enzymatic activities of stearoyl-CoA desaturase-1 (SCD-1) and Delta5 desaturase
      in streptozotocin diabetic rats. Glargine insulin depressed the hyperglycemia of
      diabetic rats at 4h, but not after 24h of injection. Fenofibrate increased the
      radioimmunoreactive insulinemia in non-diabetic rats without changing the
      glycemia. Insulin increased the mRNAs and activities of SCD-1 and Delta5
      desaturase depressed in diabetic rats. Fenofibrate increased acyl-CoA oxidase
      activity, and the mRNAs and activities of both desaturating enzymes in non
      diabetic, diabetic and insulin-treated diabetic rats, but was less effective in
      the mRNAs modification of diabetic animals. Therefore, insulin, and fenofibrate
      through PPAR-alpha activation, enhance liver mRNAs and activities of SCD-1 and
      Delta5 desaturases independently and synergistically through different
      mechanisms. Insulin and fenofibrate independently increased the 18:1/18:0 ratio
      in liver lipids, increasing the fluidity of the membranes. The 20:4/18:2 ratio
      was maintained. Fenofibrate increased palmitic acid, but decreased stearic acid
      percentage in liver lipids.

PMID- 16099632
TI  - Benefits of low weekly doses of methotrexate in steroid-dependent asthmatic
      patients. A double-blind, randomized, placebo-controlled study.
AB  - BACKGROUND: Though several drugs have been tested, the choice of the ideal
      steroid-sparing agent in steroid-dependent asthmatic patients remains unclear.
      Our objective was to evaluate the efficacy and tolerance of methotrexate in low
      weekly doses in order to decrease chronic oral steroid requirements in asthmatic
      patients. METHODS:  DESIGN: double blind randomized placebo-controlled study.
      SETTING: The study was performed in a 760-bed teaching hospital. PATIENTS: 46
      steroid-dependent asthmatic patients were randomized. INTERVENTIONS: PATIENTS
      received 10mg of methotrexate or placebo once weekly for a year. The 6
      methylprednisolone was progressively tapered (2mg/day every two weeks) until FEV1
      diminished by 5% or more; 6-methylprednisolone was then increased until the
      previous FEV1 was reached, and the procedure was repeated throughout follow-up.
      MEASUREMENTS: Blood and urine analyses and bone densitometry were performed at
      entry and at the end of the study. Pulmonary function was tested monthly during
      the first three months and then every three months until the end. RESULTS: Thirty
      nine patients were evaluated at interim analysis. A 54.8% decrease (9.5+/-4.9
      mg/day) in 6-methylprednisolone dose was observed in the methotrexate group and a
      4.4% decrease (0.5+/-7.2 mg/day) in the placebo group (P<0.001). There was no
      significant decrease of FEV1 in either group. No changes in bone metabolism were
      observed except for a non-statistically significant increase in osteocalcin
      levels in the treated group compared to a decrease in the placebo group. Toxicity
      was mild. CONCLUSIONS: (1) Methotrexate is an effective steroid-sparing agent.
      (2) A dosage lower than the one recommended in the literature is effective. (3)
      Tolerance is good. (4) No benefit or detrimental effects in bone metabolism were
      observed after one year.

PMID- 16099633
TI  - The regulation of cadherin-mediated adhesion by tyrosine
      phosphorylation/dephosphorylation of beta-catenin.
AB  - The formation of stable cell-cell adhesions by type I cadherins depends on the
      association of their cytoplasmic domain with beta-catenin, and of beta-catenin
      with alpha-catenin. The binding of beta-catenin to these partners is regulated by
      phosphorylation of at least three critical tyrosine residues. Each of these
      residues is targeted by one or more specific kinases: Y142 by Fyn, Fer and cMet;
      Y489 by Abl; and Y654 by Src and the epidermal growth factor receptor.
      Developmental and physiological signals have been identified that initiate the
      specific phosphorylation and dephosphorylation of these residues, regulating
      cadherin function during neurite outgrowth, permeability of airway epithelium and
      synapse remodeling, and possibly initiating epithelial cell migration during
      development and metastasis.

PMID- 16099634
TI  - Src and FAK signalling controls adhesion fate and the epithelial-to-mesenchymal
      transition.
AB  - Src kinase controls cellular adhesions, including cadherin-based intercellular
      adhesions and integrin-mediated cell-matrix adhesions. In epithelial cells, Src
      activation, or increased signalling from migratory growth factor receptors via
      Src, induces an adhesion switch that enhances dynamic cell-matrix adhesions and
      migratory capacity while suppressing intercellular contact. Moreover, Src and the
      associated tyrosine kinase FAK are at the heart of the recently identified
      crosstalk between integrin- and cadherin-mediated adhesions of epithelial cells,
      particularly during the epithelial-to-mesenchymal transition.

PMID- 16099635
TI  - Organising cells into tissues: new roles for cell adhesion molecules in planar
      cell polarity.
AB  - Planar cell polarity (PCP) is the coordinated organization of cells within the
      plane of the epithelium, first described in Drosophila. A Frizzled signalling
      pathway dedicated to PCP (the non-canonical Frizzled pathway) acts through
      Dishevelled and small G proteins, as does the classical Wnt pathway, but then
      diverges downstream of Dishevelled. Recent studies have demonstrated a crucial
      role for several atypical cadherin molecules (Fat, Dachsous and Flamingo) in
      controlling PCP signalling. Recent work has also indicated that the first sign of
      PCP during development is the polarized localization of PCP proteins (Frizzled,
      Flamingo, Dishevelled, etc). Exciting new data reveal that this PCP pathway is
      conserved to man.

PMID- 16099636
TI  - Integrin regulation.
AB  - Integrin signaling is bidirectional. 'Inside-out' signals regulate integrin
      affinity for adhesive ligands, and ligand-dependent 'outside-in' signals regulate
      cellular responses to adhesion. Integrin extracellular domains are yielding to
      high-resolution structural analyses, and intracellular proteins involved in
      integrin signaling are being identified. However, a key unresolved question is
      how integrins propagate signals across the plasma membrane.

PMID- 16099637
TI  - Mammalian cadherins and protocadherins: about cell death, synapses and
      processing.
AB  - Cadherins have been known for a long time to be key elements in many important
      biological processes. In particular, the role of classical cadherins in mediating
      adhesion has been examined in great detail. Over recent years, the accumulation
      of experimental tools and mice mutants has allowed more refined analysis of
      cadherin functions, and new aspects such as signaling and synapse dynamics have
      become the center of interest. In addition, the study of mice lacking the entire
      protocadherin-gamma cluster shed the first light on a possible novel function of
      members of this cadherin family in synapse formation and cell survival during
      development.

PMID- 16099638
TI  - Cell migration during gastrulation.
AB  - As the gateway to shaping the body plan, gastrulation is an important problem in
      developmental biology, and recent advances in cell biology have overcome some of
      the limitations of past approaches to learning how genes control reshaping of
      embryonic tissues. The use of fluorescent tracer dyes and live cell imaging
      methods to evaluate at the cellular level the results of genetic and molecular
      manipulations has advanced our understanding of the cell motility and contact
      behavior underlying tissue remodeling during gastrulation.

PMID- 16099639
TI  - Molecular control of cell polarity and asymmetric cell division in Drosophila
      neuroblasts.
AB  - In the embryonic central nervous system of the fruit fly Drosophila, most neurons
      and glial cells are generated by asymmetric division of neural stem cells called
      neuroblasts. Several genes have been identified that are required for the
      establishment of neuroblast polarity, for the asymmetric segregation of cell fate
      determinants and for the proper orientation and geometry of the mitotic spindle.
      However, little was known about the interactions between these genes and their
      respective gene products. It has emerged that most of the relevant proteins are
      assembled into three major protein complexes whose molecular interactions are
      conserved in evolution.

PMID- 16099640
TI  - Effects of the type of dietary fat on acetylcholine-evoked amylase secretion and
      calcium mobilization in isolated rat pancreatic acinar cells.
AB  - Olive oil is a major component of the Mediterranean diet, and its role in human
      health is being actively debated. This study aimed to clarify the mechanism of
      pancreatic adaptation to dietary fat. For this purpose, we examined whether
      dietary-induced modification of pancreatic membranes affects acinar cell function
      in response to the secretagogue acetylcholine (ACh). Weaning male Wistar rats
      were assigned to one of two experimental groups and fed for 8 weeks with a
      commercial chow (C) or a semisynthetic diet containing virgin olive oil as
      dietary fat (OO). The fatty acid composition of pancreatic plasma membranes was
      determined by gas-liquid chromatography. For assessment of secretory function,
      viable acini were incubated with ACh and amylase of supernatant was further
      assayed with a substrate reagent. Changes in cytosolic Ca(2+) concentration in
      response to ACh were measured by fura-2 AM fluorimetry. Compared to C rats,
      pancreatic cell membranes of OO rats had a higher level of monounsaturated fatty
      acids and a lower level of both saturated and polyunsaturated fatty acids, thus,
      reflecting the type of dietary fat given. Net amylase secretion in response to
      ACh was greatly enhanced after OO feeding, although this was not paralleled by
      enhancement of ACh-evoked Ca(2+) peak increases. In conclusion, chronic intake of
      diets that differ in the fat type influences not only the fatty acid composition
      of rat pancreatic membranes but also the responsiveness of acinar cells to ACh.
      This mechanism may be, at least in part, responsible for the adaptation of the
      exocrine pancreas to the type of fat available.

PMID- 16099641
TI  - Protection of mammalian cell used in biosensors by coating with a polyelectrolyte
      shell.
AB  - In order to detect xenoestrogens which induce perturbations of mammalian cells,
      design of biosensor using a mammalian cell line enable to detect these compounds
      is necessary. MELN cell line is suitable to detect estrogen activity, since they
      are stably transfect with an estrogen regulated luciferase gene. To realize this
      biosensor, it appeared necessary to add a protection to the mamalian cell, which
      is devoided, of the wall protecting yeasts or plant cells. With this aim in view,
      MELN cells have been isolated with a polyelectrolyte shell using the layer-by
      layer technique. Among several polyelectrolyte-couples, the best cell survival
      (>80%) was obtained by alternating the polycation poly-diallyldimethyl ammonium
      chloride layer and the negatively charged poly-styrene sulfonate. We observed
      that the composition of the buffer used for layer-deposition was crucial to
      preserving cell viability, e.g. potassium ions were preferred to sodium ions
      during the coating. Furthermore, viability was increased when cells were allowed
      to recover for 2 h between each bilayer deposition. The use of engineered
      mammalian cells that synthesize luciferase as a response to exposure to
      estradiol, demonstrated that coating not only permits cell survival, but also
      allows essential metabolic functions, such as RNA and protein synthesis to take
      place. Capsule formation allows free diffusion of small molecules, while it
      prevents internalization in the cells of proteins larger than 60 kDa.

PMID- 16099642
TI  - Oligosaccharide microarrays fabricated on aminooxyacetyl functionalized glass
      surface for characterization of carbohydrate-protein interaction.
AB  - Carbohydrate-protein interactions play important biological roles in biological
      processes. But there is a lack of high-throughput methods to elucidate
      recognition events between carbohydrates and proteins. This paper reported a
      convenient and efficient method for preparing oligosaccharide microarrays,
      wherein the underivatized oligosaccharide probes were efficiently immobilized on
      aminooxyacetyl functionalized glass surface by formation of oxime bonding with
      the carbonyl group at the reducing end of the suitable carbohydrates via
      irreversible condensation. Prototypes of carbohydrate microarrays containing 10
      oligosaccharides were fabricated on aminooxyacetyl functionalized glass by
      robotic arrayer. Utilization of the prepared carbohydrate microarrays for the
      characterization of carbohydrate-protein interaction reveals that carbohydrates
      with different structural features selectively bound to the corresponding lectins
      with relative binding affinities that correlated with those obtained from
      solution-based assays. The limit of detection (LOD) for lectin ConA on the
      fabricated carbohydrate microarrays was determined to be approximately 0.008
      microg/mL. Inhibition experiment with soluble carbohydrates also demonstrated
      that the binding affinities of lectins to different carbohydrates could be
      analyzed quantitatively by determining IC(50) values of the soluble carbohydrates
      with the carbohydrate microarrays. This work provides a simple procedure to
      prepare carbohydrate microarray for high-throughput parallel characterization of
      carbohydrate-protein interaction.

PMID- 16099643
TI  - How microRNAs control cell division, differentiation and death.
AB  - After the milestone discovery of the first microRNA in 1993, the past five years
      have seen a phenomenal surge of interest in these short, regulatory RNAs. Given
      that 2% of all known human genes encode microRNAs, one main goal is to uncover
      microRNA function. Although it has been more difficult to assign function to
      microRNAs in animals than it has been in plants, important roles are emerging: in
      invertebrates, microRNAs control developmental timing, neuronal differentiation,
      tissue growth and programmed cell death. Functional studies in zebrafish and mice
      point toward important roles for microRNAs during morphogenesis and
      organogenesis. Finally, microRNAs might regulate viral infection and human
      cancer.

PMID- 16099644
TI  - Bacterial chromatin.
AB  - Recent studies have revealed that the bacterial nucleoid is a dynamic entity that
      alters its overall structure in response to changes in both growth rate and
      growth phase. These structural changes are correlated with, and might be driven
      by, changes in the distribution and utilization of DNA supercoiling. In turn,
      these parameters in addition to the delimitation of topological domains are
      dependent both on the relative proportions of the abundant nucleoid-associated
      proteins and on transcriptional activity. The domain structure itself is dynamic.

PMID- 16099645
TI  - Transcriptional regulation by WT1 in development.
AB  - The Wilms' tumour suppressor protein, WT1, plays a central role in the
      development of the genitourinary system and also other organs and tissues. WT1
      can act as a transcriptional regulator or as an RNA processing factor in an
      isoform-dependent manner. The mechanisms that are used by WT1 to regulate
      transcription, and its associated target genes have been difficult to study, in
      part because the transcription function of WT1 is highly context-dependent.
      Recent studies have provided new insights into how WT1 achieves this specificity
      and have uncovered new target genes that are regulated by WT1 during development.
      In addition, ongoing studies of transgenic animals and analyses in kidney explant
      systems have revealed further roles for WT1 in development.

PMID- 16099646
TI  - Recovery of oil components of okara by ethanol-modified supercritical carbon
      dioxide extraction.
AB  - Recovery of the oil components of okara by ethanol-modified supercritical carbon
      dioxide extraction was investigated at 40-80 degrees C temperature and 12-30 MPa
      pressure. In a typical run (holding period of 2 h, continuous flow extraction of
      5 h), results indicated that the oil component could be best obtained with a
      recovery of 63.5% at relatively low temperature of 40 degrees C and mild pressure
      of 20 MPa in the presence of 10 mol% EtOH as entrainer. Based on gas
      chromatography-mass spectrometry (GC-MS) analysis, the extracts consisted mainly
      of fatty acids and phytosterols, and traces of decadienal. Folin-Ciocalteau
      estimates of total phenols showed that addition of EtOH as entrainer increased
      the yield and the amount of phenolic compounds in the extracts. The amounts of
      two primary soy isoflavones, genistein and daidzein, in the extracts also
      increased with increasing amount of EtOH.

PMID- 16099647
TI  - Graft copolymerization of methyl methacrylate onto Bombyx mori initiated by
      semiconductor-based photocatalyst.
AB  - Methyl methacrylate (MMA) was graft copolymerized onto Bombyx mori fibre (natural
      silk). The graft copolymerization was carried out by photopolymerization of MMA
      using semiconductor particles (CdS) as photocatalyst in the presence of visible
      light. The effect of additives like triethylamine (Et(3)N) and ethylene glycol on
      graft copolymerization was studied. We have achieved 2-10% graft conversion with
      10-20% homopolymer formation. After removal of the homopolymer, the graft
      copolymer (grafted fibre) was characterized by scanning electron microscopy
      (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning
      calorimetry (DSC). The chemical resistance of grafted fibre was compared with
      virgin one.

PMID- 16099648
TI  - 1,8-Naphthyridin-4-one derivatives as new ligands of A2A adenosine receptors.
AB  - A series of 1,8-naphthyridine derivatives bearing various substituents in
      position 3, 4, and 7 of the heterocyclic nucleus have been synthesized and
      evaluated for their affinity at the bovine and human adenosine receptors. The new
      compounds were found to lack the affinity toward A(1)AR, whereas many of them are
      able to acquire an interesting affinity and selectivity for the A(2A)AR.

PMID- 16099649
TI  - Glycolipids and other constituents from Desmodium gangeticum with antileishmanial
      and immunomodulatory activities.
AB  - Nineteen compounds of various classes, such as flavonoid glycosides,
      pterocarpanoids, lipids, glycolipids, and alkaloids, were isolated and identified
      from the Desmodium gangeticum whole plant. Aminoglucosyl glycerolipid (8) is
      reported here for the first time. Its structure has been elucidated by
      spectroscopic and degradation studies. This novel compound exhibited in vitro
      antileishmanial and immunomodulatory activities, as it enhanced nitric oxide (NO)
      production and provided resistance against infection established in peritoneal
      macrophages by the protozoan parasite Leishmania donovani. Another known
      compound, glycosphingolipid (cerebroside) (7) was found to possess significant in
      vitro antileishmanial and immunomodulatory activities against the same parasite.
      Other compounds were found to be inactive.

PMID- 16099650
TI  - Identification of synthetic compounds active against VRE: the role of the
      lipidated aminoglucose and the structure of glycopeptide binding pocket.
AB  - A modified vancomycin binding pocket (D-O-E ring) incorporating an alpha-hydroxy
      beta-amino acid at the AA4 position is designed and synthesized. Some of these
      compounds display potent bioactivities against both sensitive- and resistant
      strains (8 microg/ml against VREF). Both the lipidated aminoglucose and the
      structure of the 16-membered macrocycle are found to be important for the anti
      VRE activities. The polyamine appendage at the C-terminal, on the other hand,
      improved the activity against vancomycin-sensitive strains.

PMID- 16099651
TI  - Synthesis of some pyrazole derivatives and preliminary investigation of their
      affinity binding to P-glycoprotein.
AB  - A series of substituted pyrazolines were synthesized and evaluated for their
      anticancer activity and for their ability to inhibit P-glycoprotein-mediated
      multidrug resistance by direct binding to a purified protein domain containing an
      ATP-binding site and a modulator interacting region. Compounds 2a and e have been
      found to bind to P-glycoprotein with greater affinity.

PMID- 16099652
TI  - Heteroaromatic side-chain analogs of pregabalin.
AB  - A series of heteroaromatic analogs of pregabalin has been identified that possess
      anticonvulsant activity in the DBA/2 mouse model. The methods of synthesis and
      preliminary pharmacology are discussed herein.

PMID- 16099653
TI  - A new class of high affinity thyromimetics containing a phenyl-naphthylene core.
AB  - High affinity thyromimetics containing a novel phenyl-naphthylene core are
      reported. The functionalized core is readily accessible via a Suzuki coupling
      protocol. Examples of this new class of TR ligands have sub-nanomolar binding
      affinities for the TRbeta receptor and low to modest selectivity for TRbeta. They
      also exhibit an SAR that diverges from other thyromimetics that are based on the
      diaryl ether core found in 3,5,3'-triiodothyronine.

PMID- 16099654
TI  - 9H-Xanthene-9-carboxylic acid [1,2,4]oxadiazol-3-yl- and (2H-tetrazol-5-yl)
      amides as potent, orally available mGlu1 receptor enhancers.
AB  - Small molecule mGluR1 enhancers based on the lead compound (9H-xanthene-9
      carbonyl)-carbamic acid butyl ester derived from random-screening hit
      diphenylacetyl-carbamic acid ethyl ester were designed and synthesized as useful
      pharmacological tools for the study of the physiological roles mediated by mGlu1
      receptors. The synthesis and the structure-activity relationship of this new
      class of positive allosteric modulators of mGlu1 receptors will be discussed in
      detail.

PMID- 16099655
TI  - Stride cycle influences on goal-directed head movements made during walking.
AB  - Horizontal head movements were studied in six subjects as they made rapid
      horizontal gaze adjustments while walking. The aim of the present research was to
      determine if gait cycle events alter the head movement response to a visual
      target acquisition task. Gaze shifts of approximately 40 degrees were elicited by
      a step change in the position of a visual target from a central location to a
      second location in the left or right horizontal periphery. The timing of the
      target position change was constrained to occur at 25%, 50%, 75% and 100% of the
      stride cycle. The trials were randomly presented as the subjects walked on a
      treadmill at their preferred speed (range: 1.25-1.48 m/s, mean: 1.39+/-0.09 m/s).
      Analyses focused on the movement onset latencies of the head and eyes and on the
      peak velocity and saccade amplitude of the head movement response. The head and
      eye movement onset latencies were not affected by either the direction of the
      target change or the point in the gait cycle during which the target relocation
      occurred. However, the presence of an interaction between the gait cycle events
      and the direction of the visual target shift for both the amplitude and peak
      velocity of the head movement response indicates that the head movement responses
      to visual target changes can be influenced by the phase of the gait cycle during
      which the target relocation takes place.

PMID- 16099656
TI  - Tyrosine-phosphorylated bacterial effector proteins: the enemies within.
AB  - The tyrosine phosphorylation of proteins has a central role during signal
      transduction in eukaryotes. Recent progress shows that tyrosine phosphorylation
      is also a common feature of several effector proteins translocated by bacterial
      type III and type IV secretion systems. The involvement of these secretion
      systems in disease development is exemplified by a variety of pathogenic
      processes: pedestal formation (Tir of EPEC and Citrobacter), cell scattering
      (CagA of Helicobacter), invasion (Tarp of Chlamydia) and possibly proinflammatory
      responses and cell proliferation (BepD-F of Bartonella). The discovery that
      different bacterial pathogens use this common strategy to subvert host-cell
      function suggests that more examples will soon emerge.

PMID- 16099657
TI  - New trends in antigen uptake in the gut mucosa.
AB  - The mucosa represents a large surface of the human body that is in contact with
      the external environment. Mucosal tissues are colonized by an extremely dense and
      diverse micro flora of commensal bacteria, which compete with the growth of
      pathogenic strains. The mucosal sites continuously sample foreign material via
      specific cells, such as M cells and dendritic cells. Many new ways of antigen
      uptake have been described recently, especially by M cells and dendritic cells in
      the intestine. Depending on various factors, antigen presentation in the mucosa
      can lead to tolerance or initiation of an immune response. Mucosal vaccine
      strategies will certainly require eliciting specific antigen uptake because this
      initial step has a crucial role in controlling the outcome of immune responses.

PMID- 16099658
TI  - Necrotising fasciitis following anterior cruciate ligament reconstruction. A case
      report.
AB  - Necrotising fasciitis is a rapidly progressive and life threatening soft tissue
      infection that primarily involves the superficial fascia. It can be a difficult
      condition to diagnose in its early stages and requires aggressive surgical and
      supportive management if devastating consequences are to be avoided. We describe
      a case of necrotising fasciitis following an anterior cruciate ligament (ACL)
      reconstruction using a hamstring graft. To our knowledge this has not been
      previously reported. Following radical debridement, reconstructive surgery and
      intensive physiotherapy our patient has made a satisfactory recovery.

PMID- 16099659
TI  - Isocoumarins as estrogen receptor beta selective ligands: Isomers of isoflavone
      phytoestrogens and their metabolites.
AB  - In a search for new ligands selective for the estrogen receptor beta (ERbeta), we
      prepared a series of non-steroidal compounds having an isocoumarin core
      structure. An interesting feature of these derivatives is that they bear the same
      functionalities as the well-known ERbeta -selective, isoflavone phytoestrogens
      daidzein and genistein, but in an isomeric arrangement. These compounds could be
      prepared efficiently by electrophilic cyclization of acetylenic ester precursors,
      followed by simple manipulations to introduce additional substituents. Through a
      reduction of some of the isocoumarins, we also obtained isomeric analogs of the
      isoflavone metabolites equol and dehydroequol. The compounds we prepared were
      evaluated in ER binding assays, and selected compounds were studied further in
      cell-based gene transcription assays. Several of the isocoumarins and their
      analogs are high-affinity ligands that show considerable selectivity for ERbeta
      in terms of binding affinity, and strikingly high ERbeta selectivity in terms of
      potency in gene transcription assays. Two of the best compounds, which combine
      high transcriptional potency with an ERbeta selectivity greater than 1000, should
      prove to be excellent probes of ERbeta function in vivo.

PMID- 16099660
TI  - Design and synthesis of novel androgen receptor antagonists with sterically bulky
      icosahedral carboranes.
AB  - Carboranes (dicarba-closo-dodecaboranes) are a class of carbon-containing
      polyhedral boron-cluster compounds having remarkable chemical and thermal
      stability, and hydrophobic character. These features may allow application of
      carboranes as a new hydrophobic core structure in biologically active molecules
      that interact hydrophobically with receptors. Here, we report the design and
      synthesis of novel androgen antagonists bearing a carborane moiety. These
      compounds, particularly 8a, 8c, and 9d, exhibited anti-androgenic activity
      similar to that of the well-known anti-androgen flutamide in reporter gene assay
      using NIH3T3 cells transfected with a human AR expression plasmid. The carborane
      cage seems to be a privileged hydrophobic pharmacophore for the expression of AR
      antagonistic activity.

PMID- 16099661
TI  - Dicationic near-linear biphenyl benzimidazole derivatives as DNA-targeted
      antiprotozoal agents.
AB  - A series of near-linear biphenyl benzimidazole diamidines 5a-h were synthesized
      from their respective diamidoximes (4a-h), through the bis-O-acetoxyamidoxime,
      followed by hydrogenation in glacial acetic acid/ethanol in the presence of Pd-C.
      Compounds 4a-h were obtained in three steps, starting with the Suzuki coupling
      reaction of the appropriate haloarylcarbonitriles 1a-g or 4-bromo-2
      fluorobenzaldehyde with 4-formylphenylboronic acid or 4-cyanophenylboronic acid
      to form the anticipated 4-formylbiphenyl carbonitrile analogues 2a-h. Subsequent
      condensation of the formyl derivatives 2a-h with 3,4-diaminobenzonitrile in the
      presence of sodium bisulfite or 1,4-benzoquinone gave the desired dinitriles 3a
      h, the precursors for 4a-h. All the diamidines showed strong DNA affinities, as
      judged by high Delta Tm values with poly(dA.dT)2) The compounds were quite active
      in vitro versus Trypanosoma brucei rhodesiense, giving IC50 values ranging from 3
      to 37 nM. These compounds were even more active versus Plasmodium falciparum,
      exhibiting IC50 values ranging from 0.5 to 23 nM. The compounds showed moderate
      to good activity in vivo in the STIB900 model for acute African trypanosomiasis.
      The most active compounds 5b and e gave 3/4 cures on an IP dosage of 20 mg/kg.

PMID- 16099662
TI  - A proposed molecular basis for the selective resveratrol inhibition of the PGHS-1
      peroxidase activity.
AB  - Docking results have enabled us to propose how resveratrol could act as a
      selective PGHS-1 peroxidase site inhibitor. The docking model has predicted a
      slightly less favorable DeltaG(bind) (-17.9 kcal/mol) of the resveratrol to the
      PGHS-2 peroxidase site in comparison with its corresponding binding to the PGHS-1
      (-20.4 kcal/mol). The formation of hydrogen bonds among the hydroxyl groups of
      the resveratrol phenyl rings, the backbone of Fe-heme and the carbonyl group of
      Leu294 inside the PGHS-1 peroxidase site, associated with the absence of His214
      in the backbone of PGHS-1, are essential features that are required to maintain
      the aromatic rings of the natural product parallel to the Fe-heme group and
      transverse to the peroxidase access channel promoting a large steric hindrance at
      this site and its consequent selective inhibition.

PMID- 16099663
TI  - Design, synthesis, and biological evaluation of linear 1-(4-, 3- or 2
      methylsulfonylphenyl)-2-phenylacetylenes: a novel class of cyclooxygenase-2
      inhibitors.
AB  - A group of regioisomeric 1-(methylsulfonylphenyl)-2-phenylacetylenes possessing a
      COX-2 SO(2)Me pharmacophore at the para-, meta- or ortho-position of the C-1
      phenyl ring, in conjunction with a C-2 phenyl or substituted-phenyl ring
      substituent (3-F, 3-OMe, 3-OH, 3-OAc, 4-Me), were designed for evaluation as
      selective cyclooxygenase-2 (COX-2) inhibitors. These target linear 1,2
      diarylacetylenes were synthesized via a palladium-catalyzed Sonogashira cross
      coupling reaction followed by oxidation of the respective 1-(methylthiophenyl)-2
      phenylacetylene intermediate. In vitro COX-1/COX-2 isozyme inhibition structure
      activity studies identified 1-(3-methylsulfonylphenyl)-2-(4
      methylphenyl)acetylene (12d) as a potent COX-2 inhibitor (IC(50) = 0.32 microM)
      with a high COX-2 selectivity index (SI > 320) comparable to the reference
      compound rofecoxib (COX-2 IC(50) = 0.50 microM; COX-2 SI > 200). A molecular
      modeling study where (12d) was docked in the binding site of COX-2 showed that
      the MeSO(2) COX-2 pharmacophore was positioned in the vicinity of the secondary
      COX-2 binding site near Val(523). The 1-(4-methylsulfonylphenyl)-2-(3
      acetoxyphenyl)acetylene (11f, COX-1 IC(50) = 1.00 microM; COX-2 IC(50) = 0.06
      microM; COX-2 SI = 16.7) and 1-(3-methylsulfonylphenyl)-2-(3
      acetoxyphenyl)acetylene (12f, COX-1 IC(50) = 6.5 microM; COX-2 IC(50) = 0.05
      microM; COX-2 SI = 130) regioisomers exhibited comparable COX-2 inhibition, and
      moderately lower selective COX-2 selectivity, relative to the reference drug
      celecoxib (COX-1 IC(50) = 33.1 microM; COX-2 IC(50) = 0.07 microM; COX-2 SI =
      472). The most potent anti-inflammatory agent 1-(3-methylsulfonylphenyl)-2-(4
      methylphenyl)acetylene (12d) exhibited moderate oral anti-inflammatory activity
      (ED(50)= 129 mg/kg) at 3 h postdrug administration relative to the reference drug
      celecoxib (ED(50) = 10.8 mg/kg) in a carrageenan-induced rat paw edema assay. The
      structure-activity data acquired indicate that the acetylene moiety constitutes a
      suitable scaffold (template) to design novel acyclic 1,2-diarylacetylenes with
      selective COX-2, or dual COX-1/COX-2, inhibitory activities.

PMID- 16099664
TI  - Preparation of highly substituted gamma-lactam follicle stimulating hormone
      receptor agonists.
AB  - An unusual combination of Weinreb amidation and Mitsunobu lactam formation was
      used to prepare highly substituted gamma-lactam analogues of a thiazolidinone
      follicle stimulating hormone receptor agonist. The analogue synthesis was
      stereoselective and the final products were chemically stable. Biological
      properties of the target molecules were nearly identical to those of the lead
      compound.

PMID- 16099665
TI  - Characterization of trace elements in Casearia medicinal plant by neutron
      activation analysis.
AB  - Leaves of Casearia sylvestris, Casearia decandra and Casearia obliqua plant
      species, collected at the Atlantic Forest in Brazil, were analyzed by using
      instrumental neutron activation analysis (INAA). Short and long irradiations
      using thermal neutron flux of the IEA-R1 nuclear reactor were carried out for
      these analyses. Concentrations of Ca, K and Mg were found in these samples at the
      percentage levels, Br, Cl, Fe, Mn, Na, Rb and Zn at the microg g(-1) levels and
      Co, Cr, Cs, La, and Sc at the microg kg(-1) levels. Comparisons were made among
      the element concentrations obtained in these three Casearia species and
      significant differences were found for the elements Cl, Co, Cs, Cr, La, Mn, Na
      and Sc. The precision and the accuracy of the results were evaluated by analyzing
      the certified reference materials NIST-1515 Apple Leaves and NIST-1573a Tomato
      Leaves.

PMID- 16099666
TI  - Production of the radioactive antitumoral cisplatin.
AB  - This work presents the preparation of radiolabelled cis-dichlorodiammineplatinum
      (II), CDDP*, sealed in a cadmium capsule. The irradiation of CDDP covered by
      cadmium, employing exposure times longer than 2 h, demonstrated good chemical
      purity and high specific activity. This finding allowed a better detection of in
      vivo CDDP* and suggests that it may be a good tool for studies of long-term
      biodistribution of pharmaceutical formulations containing this drug.

PMID- 16099667
TI  - Ion exchangers in radioactive waste management: natural Iranian zeolites.
AB  - Five samples of natural zeolites from different parts of Iran were chosen for
      this study. In order to characterize and determine their structures, X-ray
      diffraction and infrared spectrometry were carried out for each sample. The
      selective absorption properties of each zeolite were found by calculating the
      distribution coefficient (K(d)) of various simulated wastes which were prepared
      by spiking the radionuclides with (131)I, (99)Mo, (153)Sm, (140)La and (147)Nd.
      All the zeolite samples used in this study had extremely high absorption value
      towards (140)La; clinoptolite from Mianeh and analsite from Ghalehkhargoshi
      showed good absorption for (147)Nd; clinoptolite from Semnan and clinoptolite
      from Firozkoh showed high absorption for (153)Sm; mesolite from Arababad Tabas
      showed good absorption for (99)Mo; and finally mesolite from Arababad Tabas,
      clinoptolite from Semnan and clinoptolite from Firozkoh could be used to
      selectively absorb (131)I from the stimulated waste which was prepared. The
      natural zeolites chosen for these studies show a similar pattern to those
      synthetic ion exchangers in the literature and in some cases an extremely high
      selectivity towards certain radioactive elements. Hence the binary separation of
      radioactive elements could easily be carried out. Furthermore, these zeolites,
      which are naturally occurring ion exchangers, are viable economically and
      extremely useful alternatives in this industry.

PMID- 16099668
TI  - Study of the labeling of two novel RGD-peptidic derivatives with the precursor
      [99mTc(H2O)3(CO)3]+ and evaluation for early angiogenesis detection in cancer.
AB  - In the initial stages of tumor formation, overexpression of integrins identifying
      the RGD sequence (Arg-Gly-Asp) is observed. The aim of the present study was the
      synthesis and labeling of two novel RGD derivatives, via the precursor
      [99mTc(H2O)3(CO)3]+, as well as the radiochemical and radiopharmacological
      evaluation of the labeled products. The labeling led to the formation of a single
      product in each case (>98%), with noteworthy in vitro stability, fast blood
      clearance and elimination by the hepatobiliary and the urinary systems.

PMID- 16099669
TI  - Fetal hippocampal CA3 cell grafts enriched with FGF-2 and BDNF exhibit robust
      long-term survival and integration and suppress aberrant mossy fiber sprouting in
      the injured middle-aged hippocampus.
AB  - Cell transplants that successfully replace the lost neurons and facilitate the
      reconstruction of the disrupted circuitry in the injured aging hippocampus are
      invaluable for treating acute head injury, stroke and status epilepticus in the
      elderly. This is because apt graft integration has the potential to prevent the
      progression of the acute injury into chronic epilepsy in the elderly. However,
      neural transplants into the injured middle-aged or aged hippocampus exhibit poor
      cell survival, suggesting that apt graft augmentation strategies are critical for
      robust integration of grafted cells into the injured aging hippocampus. We
      examined the efficacy of pre-treatment and grafting of donor fetal CA3 cells with
      a blend of fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic
      factor (BDNF) for lasting survival and integration of grafted cells in the
      injured middle-aged (12 months old) hippocampus of F344 rats. Grafts were placed
      at 4 days after the kainic-acid-induced hippocampal injury and were analyzed at 6
      months post-grafting. We demonstrate that 80% of grafted cells exhibit prolonged
      survival and 71% of grafted cells differentiate into CA3 pyramidal neurons.
      Grafts also receive a robust afferent input from the host mossy fibers and
      project efferent axons into the denervated zones of the dentate gyrus and the CA1
      subfield. Consequently, the aberrant sprouting of the dentate mossy fibers, an
      epileptogenic change that typically ensues after the hippocampal injury, was
      suppressed. Thus, grafts of fetal CA3 cells enriched with FGF-2 and BDNF exhibit
      robust integration and dampen the abnormal mossy fiber sprouting in the injured
      middle-aged hippocampus. Because the aberrantly sprouted mossy fibers contribute
      to the generation of seizures, the results suggest that the grafting intervention
      using FGF-2 and BDNF is efficacious for suppressing epileptogenesis in the
      injured middle-aged hippocampus.

PMID- 16099670
TI  - Effects of hypothermia and re-warming on the inflammatory response in a murine
      multiple hit model of trauma.
AB  - INTRODUCTION: Although, hypothermia is a frequent event after trauma, it is
      unclear whether its beneficial or detrimental effects are more important. This
      study aims to quantify the effects of hypothermia and re-warming on the
      inflammatory response after fracture/hemorrhage and subsequent fracture
      stabilization with resuscitation. MATERIALS AND METHODS: Eighty-one male C57Bl/6
      mice (aged 8-10 weeks, weighing 22.0+/-3.0 g) underwent femoral fracture and
      hemorrhage followed by resuscitation and splint fixation of the fracture. Animals
      were sacrificed 3h after induction of hemorrhage and fracture. Besides a sham
      group (n=6), four experimental groups were created: A: normothermia (n=12), B:
      hypothermia after trauma (n=21), C: re-warming after resuscitation and before
      stabilization (n=21), and D: hypothermia before trauma (n=21). Groups B-D were
      further subdivided into three subgroups according to the degree of hypothermia
      (subgroup 1: 35-33 degrees C, subgroup 2: 32.9-30.0 degrees C, and subgroup 3:
      29.9-27.0 degrees C). Plasma cytokine (TNF-alpha, IL-6, and IL-10) and chemokine
      (MCP-1) concentrations were determined by ELISA, pulmonary permeability changes
      were quantified, and histological analysis of lung and liver tissues was
      performed. RESULTS: Normothermia resulted in a significantly increased early
      mortality rate. A significantly increased pro-inflammatory and decreased anti
      inflammatory responses were also observed in normothermia as compared to
      hypothermia. The extent of these changes was most pronounced in the severe
      hypothermic group. Re-warming after mild hypothermia resulted in a pro
      inflammatory response comparable to normothermia. CONCLUSION: Hypothermia has a
      beneficial effect on early survival after trauma, which appears to be independent
      of the level of hypothermia and re-warming. Re-warming, however, enhanced the pro
      inflammatory response. Further studies with a longer posttraumatic observation
      period are required to investigate the long term effects of the hypothermia and
      re-warming-induced changes on the pro- and anti-inflammatory responses.

PMID- 16099671
TI  - Effects of the active metabolite of leflunomide, A77 1726, on cytokine release
      and the MAPK signalling pathway in human rheumatoid arthritis synoviocytes.
AB  - Inflammatory cytokines or soluble factors are essential in the pathogenesis of
      rheumatoid arthritis (RA). Leflunomide is an effective disease modifying
      antirheumatic drug (DMARD) in RA. The objective of the present study was to
      evaluate for the first time the effects of A77 1726 on cytokine (interleukin (IL)
      8, IL-10, IL-11 secretion and tumor necrosis factor-alpha soluble receptor I
      (sTNFRI)) shedding in human RA fibroblast-like synoviocytes (FLS). At 100 microM,
      we observed an increase in IL-10 secretion, a decrease in IL-11 release and no
      effect on sTNFRI shedding and IL-8 secretion in IL-1beta-stimulated human RA FLS.
      Furthermore, at this dose, our results also confirmed that A77 1726 decreased IL
      6 and prostaglandin E2 (PGE2) synthesis while it increased IL-1 receptor
      antagonist secretion (IL-1Ra). The mitogen-activated protein kinases (MAPKs)
      represent an attractive target for RA because they can regulate cytokine
      expression. At 100 microM, the effect of A77 1726 on IL-10 and IL-11 secretion
      seemed to be associated with the status of p38 MAPK activation. Our results
      confirmed the immunoregulatory action of leflunomide in the cytokine network
      involved in RA pathogenesis. It could shift the balance from cytokine mediated
      inflammation to cytokine directed inhibition of the inflammatory process.

PMID- 16099672
TI  - Posttraumatic stress disorder and mortality among U.S. Army veterans 30 years
      after military service.
AB  - PURPOSE: Research suggests that posttraumatic stress disorder (PTSD) may be
      associated with later medical morbidity. To assess this, we examined all-cause
      and cause-specific mortality among a national random sample of U.S. Army veterans
      with and without PTSD after military service. METHODS: We used Cox proportional
      hazards regressions to examine the causes of death among 15,288 male U.S. Army
      veterans 16 years after completion of a telephone survey, approximately 30 years
      after their military service. These men were included in a national random sample
      of veterans from the Vietnam War Era. Our analyses adjusted for race, Army
      volunteer status, Army entry age, Army discharge status, Army illicit drug abuse,
      intelligence, age, and, additionally -- for cancer mortality -- pack-years of
      cigarette smoking. RESULTS: Our findings indicated that adjusted postwar
      mortality for all-cause, cardiovascular, cancer, and external causes of death
      (including motor vehicle accidents, accidental poisonings, suicides, homicides,
      injuries of undetermined intent) was associated with PTSD among Vietnam Theater
      veterans (N = 7,924), with hazards ratios (HRs) of 2.2 (p < 0.001), 1.7 (p =
      0.034), 1.9 (p = 0.018), and 2.3 (p = 0.001), respectively. For Vietnam Era
      veterans with no Vietnam service (N = 7,364), PTSD was associated with all-cause
      mortality (HR = 2.0, p = 0.001). PTSD-positive era veterans also appeared to have
      an increase in external-cause mortality as well (HR = 2.2, p = 0.073).
      CONCLUSIONS: Our study suggests that Vietnam veterans with PTSD may be at
      increased risk of death from multiple causes. The reasons for this increased
      mortality are unclear but may be related to biological, psychological, or
      behavioral factors associated with PTSD and warrant further investigation.

PMID- 16099673
TI  - An empirical evaluation of period survival analysis using data from the Canadian
      Cancer Registry.
AB  - OBJECTIVE: To provide an empirical evaluation of the performance of period
      analysis in comparison to traditional methods of survival analysis for predicting
      future 5-year cancer survival using data from the Canadian Cancer Registry.
      METHODS: 5-year relative survival estimates were derived by period and
      traditional methods of analysis using data available at the conclusion of 1997.
      The extent to which these estimates agreed with survival later observed for
      cancer cases diagnosed in 1997 was quantified by calculating the squared
      difference of the estimate to the corresponding relative survival ratio actually
      observed. RESULTS: Period analysis was observed to be superior to, or comparable
      with, cohort analysis in predicting the average 5-year relative survival observed
      later for virtually all individual cancer sites studied. The improvement in
      survival estimation was most pronounced for prostate cancer. Where period
      estimates did not match the eventually observed value, they were predominantly on
      the lower side. Complete analysis estimates were generally observed to be in
      between the cohort and period values. CONCLUSIONS: The period method of survival
      analysis provides more up-to-date estimates of 5-year survival than do
      traditional cohort-based methods.

PMID- 16099674
TI  - Phylogenetic analysis as a tool in molecular epidemiology of infectious diseases.
AB  - Phylogenetics is a powerful tool for microbial epidemiology, but it is a tool
      that is often misused and misinterpreted by the field. Microbial epidemiologists
      are cautioned that in order to draw any inferences about the order of descent
      from a common ancestor it is necessary to correctly root a phylogenetic tree.
      Epidemiological samples of microbial populations typically include both ancestors
      and their descendants. In order to illustrate the relationships of those
      isolates, the phylogenetic method used must be able to detect zero-length
      branches. Unweighted Pair-Group Method (UPGMA) is the phylogenetic method that is
      most widely used in microbial epidemiology. Because UPGMA cannot detect zero
      length branches, and because it places the root of the tree based on a usually
      false assumption, UPGMA is the worst possible choice among the several
      phylogenetic methods available. Because microbial epidemiology deals with
      relationships among strains within a species, rather than with relationships
      among species, recombination within those species can render phylogenetic trees
      meaningless and positively misleading. When there is evidence of significant
      recombination within the species of interest phylogenetic trees should not be
      used at all. Instead, alternative tools such as eBURST should be used to
      understand relationships among isolates.

PMID- 16099675
TI  - Method for determining the spatial position of the shoulder with ultrasound-based
      motion analyzer.
AB  - Several methods have been developed recently for the analysis of the spatial
      motion of the scapula and the arm, whereby the spatial position of shoulder bones
      is determined in static conditions by interrupting motion. The authors have
      developed a 3D motion analysis method recording scapular motion in progress with
      appropriate accuracy in the course of arm movements of various degrees. The
      objective of this study is to explore the applicability of the method developed,
      as well as to compare it with and verify it by other methods developed earlier.
      The position and displacements of shoulder bones were determined on 30 shoulders
      of 15 healthy people. The newly developed measurement method is based on the
      mechanical basic principle stating that the position and motion of a rigid body -
      in this case, the bones (segments) forming the shoulder joint -- can be
      calculated at any moment from the spatial coordinates of three points of a
      segment and any changes thereof in the course of motion. Ultrasound-based
      triplets providing the three points (fundamental points) by a segment as required
      for measurement were fixed on the sternum (modeling the trunk), the clavicle, the
      acromion (modeling the scapula), the upper arm, and the lower arm. The position
      of the sixteen anatomical points involved in the study were determined by an
      ultrasound-based pointer in the local coordinate system specified by the
      fundamental points before starting measurements. The ZEBRIS ultrasound-based
      motion analysis system was used for measuring the spatial coordinates of triplets
      in the course of continuous motion. The spatial coordinates of the designated
      anatomical points can be calculated by the method of triangulation. The method
      was calibrated by a ZEBRIS mapping (3DCAD) software commercially available, and
      the measurement error rate of the method was determined by statistical
      calculations. On the basis of calibration and error calculations it could be
      established that the accuracy and the reproducibility of the method were
      appropriate, in accordance with the limit values to be found in the literature.

PMID- 16099676
TI  - Pathophysiology of upper extremity muscle disorders.
AB  - A review of the literature on the pathophysiology of upper extremity muscle
      disorders (UEMDs) was performed. An overview is given of clinical findings and
      hypotheses on the pathogenesis of UEMDs. The literature indicates that disorders
      of muscle cells and limitations of the local circulation underlie UEMDs. However,
      these disorders identified do not necessarily lead to symptoms. The following
      mechanisms have been proposed in the literature: (1) selective recruitment and
      overloading of type I (Cinderella) motor units; (2) intra-cellular Ca(2+)
      accumulation; (3) impaired blood flow; (3b) reperfusion injury; (3.3c) blood
      vessel-nociceptor interaction; (4a) myofascial force transmission; (4b)
      intramuscular shear forces; (5) trigger points; (6) impaired heat shock response.
      The results of the review indicate that there are multiple possible mechanisms,
      but none of the hypotheses forms a complete explanation and is sufficiently
      supported by empirical data. Overall, the literature indicates that: (1)
      sustained muscle activity, especially of type I motor units, may be a primary
      cause of UEMDs; (2) in UEMDs skeletal muscle may show changes in morphology,
      blood flow, and muscle activity; (3) accumulation of Ca(2+) in the sarcoplasm may
      be the cause of muscle cell damage; (4) it seems plausible that suboptimal blood
      flow plays a role in pathogenesis of UEMDs; (5) since the presence of fiber
      disorders is not a sufficient condition for the development of UEMSDs additional
      mechanisms, such as sensitization, are assumed to play a role.

PMID- 16099677
TI  - Evidence of self-sustained motoneuron firing in young and older adults.
AB  - Motoneurons demonstrate a type of self-sustained firing behavior that seems to be
      produced by a prolonged period of depolarization caused by intrinsic long-term
      changes in the motoneuron. Such self-sustained firing behavior has previously
      been reported in human motor units. The purpose of the present study was to
      investigate the occurrence of self-sustained firing behavior in older adults.
      Eight young (mean age 24 yrs) and eight older (mean age 73 yrs) individuals
      participated in the investigation. While subjects produced light dorsiflexion
      contractions, a brief vibration stimulus was applied to the tibialis anterior
      muscle. Motor unit recordings were also obtained from the tibialis anterior
      muscle. Self-sustained firing behavior was evidenced by the appearance of new
      motor unit recruitment following vibration, even as the motor units that fired
      before the vibratory stimulus maintained a steady firing rate. The proportion of
      motor units exhibiting self-sustained firing activity was similar in both young
      and older adults (approx. 23% of trials). We conclude that self-sustained firing
      behavior is a ubiquitous phenomenon that does not seem to be affected by the
      aging process.

PMID- 16099678
TI  - Active trunk stiffness increases with co-contraction.
AB  - Trunk dynamics, including stiffness, mass and damping were quantified during
      trunk extension exertions with and without voluntary recruitment of antagonistic
      co-contraction. The objective of this study was to empirically evaluate the
      influence of co-activation on trunk stiffness. Muscle activity associated with
      voluntary co-contraction has been shown to increase joint stiffness in the ankle
      and elbow. Although biomechanical models assume co-active recruitment causes
      increase trunk stiffness it has never been empirically demonstrated. Small trunk
      displacements invoked by pseudorandom force disturbances during trunk extension
      exertions were recorded from 17 subjects at two co-contraction conditions
      (minimal and maximal voluntary co-contraction recruitment). EMG data were
      recorded from eight trunk muscles as a baseline measure of co-activation.
      Increased EMG activity confirms that muscle recruitment patterns were different
      between the two co-contraction conditions. Trunk stiffness was determined from
      analyses of impulse response functions (IRFs) of trunk dynamics wherein the
      kinematics were represented as a second-order behavior. Trunk stiffness increased
      37.8% (p < 0.004) from minimal to maximal co-activation. Results support the
      assumption used in published models of spine biomechanics that recruitment of
      trunk muscle co-contraction increases trunk stiffness thereby supporting
      conclusions from those models that co-contraction may contribute to spinal
      stability.

PMID- 16099679
TI  - Individual voxel-based analysis of gray matter in focal cortical dysplasia.
AB  - High-resolution MRI of the brain has made it possible to identify focal cortical
      dysplasia (FCD) in an increasing number of patients. There is evidence for
      structural abnormalities extending beyond the visually identified FCD lesion.
      Voxel-based morphometry (VBM) has the potential of detecting both lesions and
      extra-lesional abnormalities because it performs a whole brain voxel-wise
      comparison. However, on T1-weighted MRI, FCD lesions are characterized by a wide
      spectrum of signal hyperintensity that may compromise the results of the
      segmentation step in VBM. Our purpose was to investigate gray matter (GM) changes
      in individual FCD patients using voxel-based morphometry (VBM). In addition, we
      sought to assess the performance of this technique for FCD detection with respect
      to lesion intensity using an operator designed to emphasize areas of hyperintense
      T1 signal. We studied 27 patients with known FCD and focal epilepsy and 39
      healthy controls. We compared the GM map of each subject (controls and patients)
      with the average GM map of all controls and obtained a GM z-score map for each
      individual. The protocol being designed to achieve a maximal specificity, no
      differences in GM concentration were found in the control group. The z-score maps
      showed an increase in GM that coincided with the lesion in 21/27 (78%) patients.
      Five of the six remaining patients whose lesions were not detected by VBM
      presented with a strong lesion hyperintensity, and a significant part of their
      lesion was misclassified as white matter. In 16/27 (59%) patients, there were
      additional areas of GM increase distant from the primary lesion. Areas of GM
      decrease were found in 8/27 (30%) patients. In conclusion, individual voxel-based
      analysis was able to detect FCD in a majority of patients. Moreover, FCD was
      often associated with widespread GM changes extending beyond the visible lesion.
      In its current form, however, individual VBM may be unable to detect lesions
      characterized by strong signal intensity abnormalities.

PMID- 16099680
TI  - Physical and physiological consequences of passive intra-oral shimming.
AB  - Imaging the human orbitofrontal cortex (OFC) with fMRI is problematic due to the
      proximity of this region to the air-filled sinuses, which causes susceptibility
      artifacts. Placing a strongly diamagnetic material into the mouth ('mouthshim')
      of a human volunteer can significantly reduce the artifacts in this region. Using
      the same combined olfactory and visual fMRI paradigm, we compared brain
      activation and static B0 field maps of participants being scanned both with and
      without the 'mouthshim'. Results demonstrate that the device improves the B0
      field homogeneity within OFC, resulting in significantly stronger BOLD activation
      in this region. However, the device also caused both increased head motion and
      reduced activation in insular cortices due to more frequent swallowing and
      tactile stimulation of the tongue. The 'mouthshim' should only, therefore, be
      used where sensitivity in OFC regions is paramount.

PMID- 16099681
TI  - Harry's first and second readers.

PMID- 16099683
TI  - Estimating and comparing diagnostic tests' accuracy when the gold standard is not
      binary.
AB  - RATIONALE AND OBJECTIVES: Investigators often need to assess the accuracies of
      diagnostic tests when the gold standard is not binary-scale. The objective of
      this article is to describe nonparametric estimators of diagnostic test accuracy
      when the gold standard is continuous, ordinal, and nominal scale. MATERIALS AND
      METHODS: A nonparametric method of estimating and comparing the area under
      receiver operating characteristic (ROC) curves, proposed by DeLong et al, is
      extended to situations in which the gold standard is not binary. Two examples
      illustrate the methods. RESULTS: Measures of diagnostic test accuracy, their
      variance, and tests for comparing two diagnostic tests' accuracies in paired
      designs are presented for situations in which the gold standard is continuous,
      ordinal, and nominal scale. These summary measures of diagnostic test accuracy
      are analogous in form and interpretation to the area under the ROC curve.
      CONCLUSION: Dichotomizing the outcomes of a gold standard so that traditional ROC
      methods can be applied can lead to bias. The methods described here are useful
      for assessing and comparing summary test accuracy when the gold standard is not
      binary scale. They have limitations similar to other summary indices.

PMID- 16099684
TI  - Ultrasmall superparamagnetic iron-oxide-enhanced MR imaging of normal bone marrow
      in rodents: original research original research.
AB  - RATIONALE AND OBJECTIVES: The objective is to compare three different ultrasmall
      superparamagnetic iron oxides (USPIOs) for magnetic resonance (MR) imaging of
      normal bone marrow in rodents. MATERIALS AND METHODS: Femoral bone marrow in 18
      Sprague-Dawley rats was examined by using MR imaging before and up to 2 and 24
      hours postinjection (PI) of 200 mumol of Fe/kg of SHU555C (n = 6), ferumoxtran-10
      (n = 6), or ferumoxytol (n = 6), using T1-weighted (50 ms/1.7 ms/60 degrees =
      repetition time [TR]/echo time [TE]/flip angle) and T2*-weighted (100 ms/15 ms/38
      degrees = TR/TE/flip angle) three-dimensional spoiled gradient recalled echo
      sequences. USPIO-induced bone marrow was evaluated qualitatively and quantified
      as signal-to-noise ratio (SNR) and change in signal intensity (DeltaSI) values. A
      mixed-effect model was fitted to the SNR and DeltaSI values, and differences
      among USPIOs were tested for significance by using F tests. RESULTS: At 2 hours
      PI, all three USPIOs showed marked positive signal enhancement on T1-weighted
      images and a corresponding marked signal loss on T2*-weighted images. At 24 hours
      PI, the T1 effect of all three USPIOs disappeared, whereas T2*-weighted images
      showed persistent signal loss on SHU555C and ferumoxytol-enhanced MR images, but
      not ferumoxtran-10-enhanced MR images. Corresponding SNR and DeltaSI values on
      T2*-weighted MR images at 24 hours PI were significantly different from baseline
      for SHU555C and ferumoxytol, but not ferumoxtran-10. CONCLUSION: All three USPIO
      contrast agents, ferumoxtran-10, ferumoxytol, and SHU555C, can be applied for MR
      imaging of bone marrow. Ferumoxtran-10 apparently reveals a different kinetic
      behavior in bone marrow than ferumoxytol and SHU555C.

PMID- 16099685
TI  - Truly hybrid X-ray/MR imaging: toward a streamlined clinical system.
AB  - RATIONALE AND OBJECTIVE: We have installed an improved X-ray/MR (XMR) truly
      hybrid system with higher imaging signal-to-noise ratio (SNR) and versatility
      than our first prototype. In our XMR design, a fixed anode X-ray fluoroscopy
      system is positioned between the two donut-shaped magnetic poles of a 0.5T GE
      Signa-SP magnet (SP-XMR). This paper describes the methods for increased
      compatibility between the upgraded x-ray and MR systems that have helped improve
      patient management. MATERIALS AND METHODS: A GE OEC 9800 system (GE OEC Salt Lake
      City, UT) was specially reconfigured for permitting X-ray fluoroscopy inside the
      interventional magnet. A higher power X-ray tube, a new permanent tube mounting
      system, automatic exposure control (AEC), remote controlled collimators, choice
      of multiple frame rates, DICOM image compatibility, magnetically shimmed X-ray
      detector, X-ray compatible MR coil, and better RF shielding are the highlights of
      the new system. A total of 23 clinical procedures have been conducted with SP-XMR
      guidance of which five were performed using the new system. RESULTS: The 70%
      increased power for fluoroscopy, and a new 6 times higher power single frame
      imaging mode, has improved imaging capability. The choice of multiple imaging
      frame rates, AEC, and collimator control allow reduction in X-ray exposure to the
      patient. The DICOM formatting has permitted easy transfer of clinical images over
      the hospital PACS network. The increased MR compatibility of the detector and the
      X-ray transparent MR coil has enabled faster switching between X-ray and MR
      imaging modes. CONCLUSION: The improvements introduced in our SP-XMR system have
      further streamlined X-ray/MR hybrid imaging. Additional clinical procedures could
      benefit from the new SP-XMR imaging.

PMID- 16099686
TI  - MRI-guided focused ultrasound surgery of uterine leiomyomas.
AB  - Uterine fibroids are the most common pelvic tumors in women and are a significant
      cause of morbidity for women of reproductive age. Today, there are a variety of
      less invasive alternatives available to hysterectomy, such as myomectomy,
      hormonal therapy, uterine artery embolization, and more recently magnetic
      resonance-guided focused ultrasound surgery (MRgFUS). With this technique,
      ultrasound waves are focused through intact skin of the anterior abdominal wall
      resulting in localized thermal tissue ablation, monitored by online MR
      temperature control. By using an effective combination of image guidance and
      energy delivery, MRgFUS therefore allows for preservation of uterine function
      while obviating the need for a minimally invasive procedure or surgery.

PMID- 16099687
TI  - Impact of electromagnetic field exposure limits in Europe: is the future of
      interventional MRI safe?
AB  - The European Union (EU) has recently introduced a directive that aims to protect
      workers from adverse effects of exposure to electromagnetic fields. All countries
      within the EU are required to incorporate this directive into their national law
      by 2008. This legislation applies to all types of occupational exposure to
      electromagnetic fields with frequencies from 0 Hz to 300 GHz. It has dramatic
      implications for interventional magnetic resonance (MR) imaging, because workers
      who are close to the MR scanner while scanning is taking place are exposed at
      levels substantially above the exposure limits. This is especially the case for
      time-varying magnetic fields in the 110 Hz-5 kHz range, which includes the field
      from the imaging gradients. In this article, the scientific evidence on which the
      limits are based is brought into question. It is concluded that an urgent review
      of the directive is required and that more research, especially at MR gradient
      frequencies, is needed.

PMID- 16099688
TI  - MRI-guided and monitored radiofrequency tumor ablation.

PMID- 16099689
TI  - MR Imaging-guided percutaneous tumor ablation.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study is to compare the feasibility
      and precision of renal artery angioplasty and stent placement using two different
      MR scanners. MATERIALS AND METHODS: MR imaging-guided angioplasty and stent
      placements were performed on seven pigs using 0.2 and 1.5 T scanners (Magnetom
      Open and Magnetom Sonata, Siemens Medical Solutions, Erlangen, Germany). For
      guidance of catheters, guide wires and stents susceptibility artifact-based
      tracking was used. The end point of each intervention was to position a stent in
      the renal artery with its proximal end at the level of the aortic wall. Procedure
      time and stent position were evaluated. RESULTS: Catheterization, angioplasty,
      and stent placement were feasible using MRI guidance at both 0.2 and 1,5 Tesla.
      At 1.5 T all catheter manipulations and interventions were performed in less than
      30 minutes. At 0.2 T the interventions took up to 90 minutes. No significant
      difference in the stent deviation was noted between the two scanners. CONCLUSION:
      The use of a high-performance 1.5 T scanner helped to reduce the procedure time
      to half of that of a low-field system. Since no difference in stent placement
      precision was noted, a dedicated MR-stent might be mandatory for more precise
      stent placement.

PMID- 16099690
TI  - A review of technical advances in interventional magnetic resonance imaging.
AB  - Initial research in the development of interventional magnetic resonance (MR)
      imaging in the late 1980s and early to mid-1990s focused on pulse sequences,
      devices, and clinical applications. This focus was largely a result of the
      limited number of areas in which the academic research community leading the
      development could provide innovation on the MR systems of the time. However,
      during the past decade, computational power, higher bandwidth graphical displays,
      faster computer networks, improved pulse sequence architectures, and improved
      technical specifications have accelerated the pace of development on modern MR
      systems. Today, it is the combination of multiple system factors that are
      enabling the future of interventional MR. These developments, their impact on the
      field, and newly emerging applications are described.

PMID- 16099691
TI  - Comparing 0.2 tesla with 1.5 tesla intraoperative magnetic resonance imaging
      analysis of setup, workflow, and efficiency.
AB  - RATIONALE AND OBJECTIVES: To compare low-field with high-field intraoperative
      magnetic resonance imaging (MRI) in respect to setup, workflow, and efficiency.
      MATERIALS AND METHODS: A total of 750 patients were investigated either with a
      0.2 T (March 1996-July 2001) or a 1.5 T (April 2002-August 2004) MRI system
      adapted for intraoperative use. RESULTS: With the low-field setup, 330 patients
      were examined in 65 months; with the high-field setup, 420 patients were examined
      in 29 months, which is a 2.8-fold increase in cases per month (14.5 versus 5.1)
      reflecting improved ease of use. Concerning intraoperative workflow, the time for
      preparation to start intraoperative imaging decreased fivefold (2 minutes instead
      of 10 minutes); navigation was applied more often with 57% versus 51% (240/420
      versus 167/330), whereas functional data were integrated in 35% versus 39%
      (84/240 versus 65/167). Application of navigation updates was doubled (22% versus
      11%; 53/240 versus 18/167). Image acquisition time was reduced by a factor of
      two, allowing a more detailed imaging protocol, whereas the image quality is
      clearly improved in the high-field setup, where there was no difference between
      the standard preoperative image quality compared with the intraoperative quality.
      This contributed to an increased detection of tumor remnants and extended
      resections in pituitary (36% versus 29%; 47/129 versus 17/59) and glioma surgery
      (41% versus 26%; 38/93 versus 28/106). CONCLUSION: Compared with the low-field
      setup, the high-field setup results not only in clearly superior image quality
      and increased imaging armamentarium, contributing to increased rates of detected
      tumor remnants, but also in a distinct improvement of intraoperative workflow.
      Furthermore, intraoperative high-field MRI offers various modalities beyond
      standard anatomic imaging, such as magnetic resonance spectroscopy, diffusion
      tensor imaging, and functional MRI.

PMID- 16099692
TI  - MRI-Guided interventions.

PMID- 16099693
TI  - Recombinant factor VIIa in the treatment of intractable bleeding in vascular
      surgery.
AB  - Intractable bleeding unresponsive to conventional haemostatic measures is an
      uncommon but potentially life threatening surgical complication. Several studies
      have suggested that recombinant factor VIIa (rVIIa), a genetically engineered
      substitute for endogenous factor VIIa may have therapeutic application in
      patients with uncontrollable haemorrhage not previously diagnosed with
      coagulopathy. We report our experience of rVIIa use in eight such vascular
      surgery patients who developed life-threatening non-surgical haemorrhage either
      intra-operative or post-operatively. In all but one patient a marked clinical
      improvement was noted following treatment with rVIIa with significantly less
      transfusion, and obvious haemostasis associated with haemodynamic stability
      without adverse thrombotic complications.

PMID- 16099694
TI  - The effect of pravastatin on intima media thickness of the carotid artery in
      patients with normal cholesterol.
AB  - OBJECTIVE: Carotid intima media thickness (IMT) is a good indicator of the
      severity of atherosclerotic disease. Statins have been found to reduce carotid
      IMT in patients with hypercholesterolaemia. The aim of this study was to
      investigate if pravastatin is effective in reducing IMT in normocholesterolaemic
      patients with carotid artery disease. METHODS: Patients with carotid artery
      stenosis and normal cholesterol levels who were not on a statin, were recruited.
      Patients were randomised to receive pravastatin or placebo daily. Serum
      concentration of cholesterol and IMT of common carotid arteries were measured
      before randomisation and at 3 monthly intervals thereafter, for 9 months. IMT was
      analysed to give the mean of a standardised 2 cm of the common carotid artery
      (CCA). Results are expressed as median (IQR) and comparison made using the
      Wilcoxon signed ranks test. RESULTS: Fifty-four patients were examined. Twenty
      eight patients were randomised to active treatment. There was no difference in
      demographic details and co-morbid states between the two groups. A significant
      reduction in cholesterol concentration was observed from 3 months in patients
      randomised to the pravastatin group [5.14(4.72-5.88) vs. 4.11(3.44-5.33), p <
      0.05], while there was also a significant decrease in combined IMT form 6 months
      [1.53(1.36-1.87) vs. 1.41 (1.33-1.78), p < 0.05]. CONCLUSIONS: The results
      demonstrate that pravastatin reduces intima media thickness of the common carotid
      artery in normocholesterolaemic patients with moderate carotid stenosis.

PMID- 16099695
TI  - Neovascularization after great saphenous vein ablation.
AB  - OBJECTIVE: To determine the prevalence, distribution, and flow characteristics of
      intraluminal neovascularization in patients undergoing great saphenous vein (GSV)
      endovenous laser (EVLT) or radiofrequency ablation (RFA). METHODS: Duplex
      ultrasound (DU) was performed in patients undergoing EVLT or RFA before, during,
      and after their procedures. Follow-up included assessment for deep venous
      thrombosis and obliteration. When new vessels were identified, the source,
      extent, direction, and location of flow were noted. Flow channel diameters were
      measured and the resistivity index (RI) was used to characterize the flow
      patterns. RESULTS: A total of 102 venous ablations were performed of which 46
      were RFA, and 56 EVLT. Arterio-venous fistulae (AVF) were found in five patients
      that were not identified by DU prior to intervention. Involved segments had
      variable length and multiple channels (mean diameter 2.2mm). No patient had local
      or systemic symptoms related to the AVF. The mean RI was 0.42, consistent with an
      AVF. The perivenous arteries feeding the AVF had enhanced flow but a
      significantly higher RI (0.63, p<0.001). CONCLUSION: Multiple small vessels were
      found directly adjacent to the involved vein segments forming small AVF within
      the obliterated vein. The prevalence of AVF in the ablated GSV was 5%. This
      process may be responsible for recanalization or recurrence after endovenous
      ablation procedures.

PMID- 16099696
TI  - Prions and exosomes: from PrPc trafficking to PrPsc propagation.
AB  - Exosomes are membrane vesicles released into the extracellular environment upon
      exocytic fusion of multivesicular endosomes with the cell surface. Exosome
      secretion can be used by cells to eject molecules targeted to intraluminal
      vesicles of multivesicular bodies, but particular cell types may exploit exosomes
      as intercellular communication devices for transfer of proteins and lipids among
      cells. The glycosylphosphatyidylinositol-linked prion protein (PrP) in both its
      normal (PrPc) and scrappie (PrPsc) conformation is associated with exosomes.
      Targeting of exosomes containing the normal cellular PrP could confer
      susceptibility of cells that do not express PrP to prion multiplication.
      Furthermore, exosomes bearing proteinase-K resistant PrPsc are infectious,
      suggesting a model in which exosomes secreted by infected cells could serve as
      vehicles for propagation of prions. Thus, cells may exploit the nature of
      endosome-derived exosomes to communicate with each other in normal and
      pathological situations, providing for a novel route of cell-to-cell
      communication and therefore of pathogen transmission. These findings open the
      possibility that methods to interfere with trafficking of such unconventional
      pathogens could be envisioned from insights on the mechanisms involved in exosome
      formation, secretion and targeting.

PMID- 16099697
TI  - Exosome secretion and red cell maturation: Exploring molecular components
      involved in the docking and fusion of multivesicular bodies in K562 cells.
AB  - During reticulocyte maturation, some membrane proteins and organelles that are
      not required in the mature red cell are lost. These proteins are released into
      the extracellular medium associated with vesicles present in multivesicular
      bodies (MVBs). Fusion of MVBs with the plasma membrane results in secretion of
      the small internal vesicles, termed exosomes. By studying MVBs fusion and exosome
      release in K562 cells, a human erythroleukemic cell line, we have determined the
      functional significance of Rab11 and calcium in these events. Additionally, in
      the transformation process that occurs during erythrocyte maturation,
      intracellular organelles are likely removed as a consequence of autophagic
      sequestration and degradation. We propose K562 cells as a useful tool to analyze,
      at the molecular level, the role of autophagy in the terminal differentiation of
      red cells.

PMID- 16099698
TI  - Nitrative DNA damage in inflammation and its possible role in carcinogenesis.
AB  - Chronic inflammation has long been recognized as a risk factor for human cancer
      at various sites. Examples include Helicobacter pylori-induced gastritis for
      gastric cancer, inflammatory bowel disease (ulcerative colitis and Crohn's
      disease) for colorectal cancer and chronic viral hepatitis for liver cancer. Here
      we review the role in carcinogenesis of nitrative damage to nucleic acids, DNA
      and RNA, which occurs during inflammation through the generation of reactive
      nitrogen species, such as peroxynitrite, nitroxyl, and nitrogen dioxide. Enhanced
      formation of 8-nitroguanine, representative of nitrative damage to nucleobases,
      has been detected in various inflammatory conditions. The biochemical nature of
      DNA damage mediated by reactive nitrogen species is discussed in relation to its
      possible involvement in mutations, genetic instability, and cell death. Better
      understanding of the mechanisms and role of such nitrative damage in chronic
      inflammation-associated human cancer is a necessary basis to develop new
      strategies for cancer prevention by modulating the process of inflammation.

PMID- 16099699
TI  - Acute hepatitis E virus infection in a Cuban patient.

PMID- 16099700
TI  - Efficacy and safety of tigecycline monotherapy compared with vancomycin plus
      aztreonam in patients with complicated skin and skin structure infections:
      Results from a phase 3, randomized, double-blind trial.
AB  - OBJECTIVES: To compare the effect of tigecycline monotherapy, a first-in-class,
      expanded broad spectrum glycylcycline, with the combination of vancomycin and
      aztreonam (V + A) in the treatment of complicated skin and skin structure
      infections (cSSSI). METHODS: A phase 3, double-blind study conducted in 8
      countries enrolled adults with cSSSI who required intravenous (IV) antibiotic
      therapy for > or =5 days. Patients were randomly assigned (1:1) to receive either
      tigecycline or V + A for up to 14 days. Primary endpoint was the clinical cure
      rate at the test-of-cure visit. Secondary endpoints included microbiologic
      efficacy and in vitro susceptibility to tigecycline of bacteria that cause cSSSI.
      Safety was assessed by physical examination, laboratory analyses, and adverse
      event reporting. RESULTS: A total of 596 patients were screened for enrollment,
      573 were analyzed for safety, 537 were included in the clinical modified intent
      to-treat (c-mITT) population, 397 were clinically evaluable (CE), and 228 were
      microbiologically evaluable (ME). At test-of-cure, cure rates were similar
      between tigecycline and V + A groups in the CE population (82.9% versus 82.3%,
      respectively) and in the c-mITT population (75.5% versus 76.9%, respectively).
      Microbiologic eradication rates (subject level) at test-of-cure in the ME
      population were also similar between tigecycline and V + A. Frequency of adverse
      events was similar between groups, although patients receiving tigecycline had
      higher incidence of nausea, vomiting, dyspepsia, and anorexia, while increased
      ALT/SGPT, pruritus, and rash occurred significantly more often in V + A-treated
      patients. CONCLUSIONS: This study demonstrates that the efficacy of tigecycline
      monotherapy for the treatment of patients with cSSSI is statistically noninferior
      to the combination of V + A.

PMID- 16099701
TI  - Genome reduction in the alpha-Proteobacteria.
AB  - More than 20 alpha-proteobacterial genomes are currently available. These range
      in size from 1-9 Mb and represent excellent model systems for evolutionary
      studies of the organizational features of bacterial genomes. Computational
      inferences have shown that genome reductions have occurred independently in
      lineages such as Rickettsia and Bartonella that are associated with intracellular
      lifestyles. Analyses of these reduced genomes have provided insights into the
      evolution of vector-borne transmission pathways. Further research into the
      population biology of bacteria, arthropods and vertebrate hosts will help to
      refine the biology of host-pathogen interactions and will facilitate the design
      of vaccines and vector-control programs.

PMID- 16099702
TI  - DNA damage among thyroid cancer and multiple cancer cases, controls, and long
      lived individuals.
AB  - Variation in the detection, signaling, and repair of DNA damage contributes to
      human cancer risk. To assess capacity to modulate endogenous DNA damage among
      radiologic technologists who had been diagnosed with breast cancer and another
      malignancy (breast-other, n=42), early-onset breast cancer (early-onset, age
      <or=35; n=38), thyroid cancer (n=68), long-lived cancer-free individuals (hyper
      normals, n=20) and cancer-free controls (n=49) we quantified DNA damage (single
      strand breaks and abasic sites) in untreated lymphoblastoid cell lines using the
      alkaline comet assay. Komet software provided comet tail length, % DNA in tail
      (tail DNA), comet distributed moment (CDM), and Olive tail moment (OTM)
      summarized as the geometric mean of 100 cells. Category cut-points (median and
      75th percentile) were determined from the distribution among controls. Tail
      length (for >or=75% versus below the median, age-adjusted) was most consistently
      associated with the highest odds ratios in the breast-other, early-onset, and
      thyroid cancer groups (with risk increased 10-, 5- or 19-fold, respectively, with
      wide confidence intervals) and decreased risk among the hyper-normal group. For
      the other three comet measures, risk of breast-other was elevated approximately
      three-fold. Risk of early-onset breast cancer was mixed and risk of thyroid
      cancer ranged from null to a two-fold increase. The hyper-normal group showed
      decreased odds ratios for tail DNA and OTM, but not CDM. DNA damage, as estimated
      by all comet measures, was relatively unaffected by survival time, reproductive
      factors, and prior radiation treatment. We detected a continuum of endogenous DNA
      damage that was highest among cancer cases, less in controls, and suggestively
      lowest in hyper-normal individuals. Measuring this DNA damage phenotype may
      contribute to the identification of susceptible sub-groups. Our observations
      require replication in a prospective study with a large number of pre-diagnostic
      samples.

PMID- 16099703
TI  - Nickel compound-induced DNA single-strand breaks in chromosomal and nuclear
      chromatin in human blood lymphocytes in vitro: role of oxidative stress and
      intracellular calcium.
AB  - The effects of nickel sulfate, and soluble forms of nickel carbonate hydroxide
      (NiCH), nickel subsulfide, and nickel oxide on delayed induction of DNA single
      strand breaks (DNA SSBs) in chromosomal and nuclear chromatin of human blood
      lymphocytes in culture were studied. After 46 h of initial culture in
      supplemented RPMI-1640 media at 37 degrees C, human whole blood lymphocytes in
      culture were exposed to low concentrations (0-15 microM) of different nickel (Ni)
      compounds for 2 h, whereas only RPMI-1640 medium served as control. Immediately
      after 2 h of such exposure, both control and Ni-treated cells were washed with
      the same medium and incubated further in fresh complete RPMI-1640 culture medium
      for another 24h. After a total 70 h of incubation, cells were then arrested at
      metaphase. Two hours later, the induction of DNA SSBs involving both metaphase
      chromosomal and interphase nuclear chromatin was measured using the method of
      electron microscopy in situ end-labeling. The metaphase chromosomal chromatin
      showed significantly higher DNA SSBs (as measured by an increase in immunogold
      particles per microm2 chromatin) due to 15 microM NiCH and NiO when compared to
      the corresponding control value. Both NiCH and nickel oxide produced
      significantly higher induction of DNA SSBs than those of nickel subsulfide and
      nickel sulfate in chromosomal chromatin. The DNA SSBs in chromosomal chromatin
      were found to be significantly higher than those in nuclear chromatin due to
      different Ni compounds. Overall, the genotoxic potency seems to be decreased as
      follows: NiCH>nickel oxide>or=nickel subsulfide>nickel sulfate. Pretreatment of
      human blood lymphocytes with either catalase (a H2O2 scavenger), or superoxide
      dismutase (a scavenger of O2- radical) or dimethylthiourea (a hydroxyl radical
      scavenger), or N-acetylcysteine (GSH precursor) significantly reduced DNA SSBs in
      both chromosomal and nuclear chromatin induced by NiCH, suggesting the
      involvement of different types of oxidative stress in such genotoxicity.
      Deferoxamine (a highly specific iron chelator) pretreatment prevented NiCH
      induced DNA SSBs in both chromosomal and nuclear chromatin suggesting a role of
      iron-mediated oxidative stress generating hydroxyl radical in such genotoxicity.
      Simultaneous treatment with either verapamil (an inhibitor of Ca 2+ through
      plasma membranes), or dantrolene (an inhibitor of mobilization of [Ca2+]i from
      endoplasmic reticulum), or BAPTA (a Ca2+ chelator) significantly reduced Ni
      compound-induced DNA SSBs in both chromosomal and nuclear chromatin, suggesting
      that Ni compound-induced destabilization of calcium homeostasis may also involved
      in the induction of such DNA SSBs.

PMID- 16099704
TI  - Theoretical and vibrational spectroscopic analysis of the CO stretching mode of
      cholesteryl alkanoates: the particular case of the cholesteryl acetate.
AB  - Structural and vibrational properties of the CO stretching bond of cholesteryl
      acetate and related steroids are investigated theoretically and by Micro-Raman
      spectroscopy. In this work, an analysis of the CO stretching mode for the
      cholesteryl acetate is presented. Experimental results in crystalline, isotropic
      liquid and liquid crystal phases are compared with quantum chemical calculations
      using semi empirical hamiltonians (AM1 and PM3) and the density functional
      theory. The calculations were performed on isolated molecules with different
      conformations as found on previous investigations giving strong evidence of their
      existence. Calculated frequencies are found to be very close to experiments and
      suggest the possible existence of the predicted conformers.

PMID- 16099705
TI  - Spectroscopic investigation of the novel charge-transfer complex
      [(phen)(TCNE)(12)] formed in the reaction of phenacetin with tetracyanoethylene.
AB  - The charge-transfer (CT) interaction of the electron donor phenacetin (phen) and
      the pi-electron acceptor tetracyanoethylene (TCNE) has been studied in
      CH(2)Cl(2). The results obtained indicate the formation of the novel CT-complex
      with the general formula [(phen)(TCNE)(12)]. The 1:12 stoichiometry of the
      reaction was based on photometric titration, elemental analysis, infrared,
      thermal and cyclic voltametry measurements of the formed CT-complex.

PMID- 16099706
TI  - The second-order scattering study of the Tb(III)-RNA and determination of RNA.
AB  - The second-order scattering technique (SOS), using a common spectrofluorometer,
      was first developed as a sensitive instrumental analysis method for determination
      of the ribonucleic acid (RNA). The results indicate that RNA had a weak SOS peak
      and the Tb(III) ion can greatly enhance the SOS intensity of RNA with the maximum
      peak located at 612.0 nm. Mechanism study shows that the peak results from the
      long-range assembly of Tb(III) ion on the molecular surface of RNA. At the pH
      7.50 and with cetyltrimethylammonium bromide (CTMAB) (6.0 x 10(-5)M), the
      enhanced SOS intensity was in proportion to the concentration of RNA in the range
      of 2.0 x 10(-8) to 2.0 x 10(-5)g/ml. The detection limit was 1.96 ng/ml. The
      relative standard deviation (five replicates) was within +/-5% in the linear
      range. This method has been used satisfactorily for the determination of both
      synthetic and real samples. In comparison with most other methods for the
      determination of ribonucleic acids, this method is more sensitive.

PMID- 16099707
TI  - Ultraviolet-visible spectroscopic study of 3,5-dithio-2,7-dimethyl-[1,2,4]
      triazepine: qualitative analysis of tautomeric behaviour.
AB  - Room temperature UV-vis absorption spectra of the tautomeric system 3,5-dithio
      2,7-dimethyl-[1,2,4]-triazepine in solution, in acetonitrile (CH3CN), are
      measured at different water volume percentages. The comparison of the obtained
      measures to the calculated allowed absorption transitions, using ZINDO/S package,
      reveals the coexistence of all the tautomeric forms in aprotic polar solution
      with a high dominance of the dithione form. The solute-water hydrogen bond, which
      seems to be of 1:n-type, favours the dithiol and monothiol conformers to the
      detriment of the dithione one. Further experimental investigations lead to the
      result that standing at ambient Laboratory conditions in the dark favours the
      dithione tautomeric isomer, while standing at indirect sunlight shifts the
      tautomeric equilibrium away from this species.

PMID- 16099708
TI  - Ab initio study of low-lying triplet states of the lithium dimer.
AB  - Observation of Bose-Einstein condensation in Li27 initiated the interest in the
      scattering length of two ground state lithium atoms when they approach each other
      as a radical pair triplet aSigmau+3 state. But some properties of this state are
      still unknown. In present work, a number of low-lying triplet states of lithium
      molecule are calculated by multi-configuration self-consistent field (MCSCF) and
      response techniques with account of spin-orbit coupling, spin-spin coupling and
      some other magnetic perturbations. The singlet-triplet transition probabilities
      to the ground state are also presented. Most results are connected with the
      weakly bound lowest triplet a3Sigmau+ state, whose radiative lifetime and spin
      splitting are unknown so far in spite of its great importance in Bose-Einstein
      condensation. Calculations indicate that this state has a very small spin
      splitting, lambdass=-0.01 cm-1, which is negligible in comparison with the line
      width in experimental Fourier transform spectra published so far. Similar
      splitting is obtained for the upper state of the 1(3)Sigmag+--a3Sigmau+
      transition. This is in agreement with experimental rovibronic analysis of the
      1(3)Sigmag+--a3Sigmau+ band system in which the triplet structure was not
      resolved. The radiative lifetime of the a3Sigmau+ state is predicted to exceed 10
      h.

PMID- 16099709
TI  - Electronic, infrared, and Raman spectral studies of the reaction of iodine with 4
      aminopyridine.
AB  - The reaction of iodine as an electron acceptor with the base 4-aminopyridine
      (4APY) has been investigated spectrophotometrically in chloroform at room
      temperature. The electronic absorptions, infrared and Raman spectra, photometric
      titration as well as elemental analysis of the obtained iodine complex indicate
      the formation of the pentaiodide charge-transfer complex with the general formula
      [(4APY)(2)](+)I(5)(-). The characteristic strong absorptions of I(5)(-) are
      observed around 380 and 295 nm. Far infrared and Raman spectra of the solid
      complex show the vibrations of the linear I(5)(-) ion with D(infinityh) symmetry
      at 154, 104 and 89 cm(-1) assigned to nu(s)(I--I), outer bonds, nu(s)(I--I),
      inner bonds and nu(as)(I--I) inner bonds, respectively.

PMID- 16099710
TI  - Dual fluorescence of diphenyl carbazide and benzanilide: effect of solvents and
      pH on electronic spectra.
AB  - The absorption and fluorescence spectra of benzanilide (BA) and diphenyl
      carbazide (DPC) in solvents of different polarities and pH have been analysed.
      The spectral characteristics of DPC and BA are compared with diphenyl amine
      molecule. In water and methanol, a dual fluorescence is observed for both DPC and
      BA molecules. The normal stokes shifted emission originates from a locally
      excited pi* electronic state and the large stokes shifted band is due to emission
      from a twisted intramolecular charge transfer (TICT) state. pH studies show that
      both monocations and monoanions are non-fluorescent. The excited state acidity
      constants determined by fluorimetric titration and Forster cycle methods, have
      been reported and discussed.

PMID- 16099711
TI  - Evaluation frameworks for nursing informatics.
AB  - Rigorous evaluation of informatics applications in healthcare is important so
      that the impact of such systems can be understood. Although many quantitative
      methods have been employed to evaluate informatics systems, there is a growing
      trend to utilized qualitative methods during both the formative and summative
      phases of research. Several evaluation frameworks that have been proposed
      highlight the need for both qualitative and quantitative evaluation methods in
      the development and post-implementation phases of informatics systems
      development. Recommendations regarding the timing, type and use of qualitative
      methods differ for each of these frameworks. This paper examines the strengths
      and weaknesses of the published evaluation frameworks and enumerates the
      qualitative research methods in use in each of these frameworks.

PMID- 16099712
TI  - Similar anti-mitochondrial antibody reactivity profiles in familial primary
      biliary cirrhosis.
AB  - AIMS: : Familial accumulation of primary biliary cirrhosis (PBC) has been
      documented. To examine the importance of genetic factors, we carried out family
      study of the disease with a particular focus on the reactivity profiles of anti
      mitochondrial antibodies (AMA). PATIENTS AND METHODS: : Eighty-five patients with
      PBC that we experienced in the period of 1982-2003 were investigated,
      retrospectively. Twelve patients from a total of six families were investigated
      clinically and immunologically. RESULTS: : Of the 85 patients, 5 (5.9%) were
      found to have a family history of PBC. The six PBC family relationships consisted
      of four cases of sisters and two cases of a mother and daughter. HLA haplotypes
      were identical in two cases and were half-similar in the other cases. AMA titers
      were almost the same in three families and in five of the six families, sera from
      individual members within the family showed similar AMA-reactive bands in
      immunoblotting. CONCLUSION: : The prevalence of PBC is strikingly increased in
      family members (frequency of 5.9%). Sera from PBC patients of the same family
      showed the same AMA reactivity profile, suggesting that development of AMA may be
      greatly influenced by certain underlying genetic factors. Large-scale genomic
      studies of familial PBC will be critical to identify mechanisms of disease
      susceptibility.

PMID- 16099713
TI  - A proposal of the diagnostic scale of drug-induced liver injury.

PMID- 16099714
TI  - Response to Clinical Corners case (Sleep Medicine 6/2: 83-4): Pregnancy
      associated with daytime sleepiness and nighttime restlessness.

PMID- 16099715
TI  - Sibutramine does not worsen sleep apnea syndrome: a randomized double-blind
      placebo-controlled study.
AB  - BACKGROUND: As any drug acting on the central nervous system, sibutramine might
      worsen obstructive sleep apnea-hypopnea syndrome (OSAHS). This study aims to
      assess the risk of administering sibutramine to patients with OSAHS. METHODS: We
      screened male, symptomatic OSAHS patients who presented consecutively at the
      sleep clinic. Twenty-one subjects were included, aged between 30 and 60 years,
      body mass index between 25 and 35kg/m(2) and apnea-hypopnea index (AHI) greater
      than 10AH/h. Intervention was administration of 15mg sibutramine (SB) or placebo
      (PL), at bedtime, for 1 month. Each patient underwent overnight polysomnograms
      both before entering the study and after 1 month. Outcome measures were AHI and
      sleep efficiency (SE). RESULTS: Two patients withdrew prematurely, one due to
      headache, a possible side effect. Results are from 10 patients in the SB group
      and nine in the PL group. No significant differences were seen in any of the
      groups before or after treatment in measures of SE, respiratory disturbance, body
      weight, blood pressure, cardiac or respiratory frequency. Significant reduction
      occurred in the amount of REM sleep, from 19 to 13% (P=0.04) in SB group and in
      Epworth sleepiness score in PL and SB groups. CONCLUSION: The results indicate
      that sibutramine does not worsen sleep or breathing during sleep in patients with
      OSAHS.

PMID- 16099716
TI  - Response to Clinical Corners case (Sleep Medicine 6/2: 83-4): Pregnancy
      associated with daytime sleepiness and nighttime restlessness.

PMID- 16099717
TI  - Loss of normal circadian profile of urine excretion in idiopathic restless legs
      syndrome.
AB  - BACKGROUND: This study was performed to elucidate preliminary observations of
      excessive nighttime urine excretion in idiopathic restless legs syndrome (iRLS).
      METHODS: Seventeen patients, with normal serum creatinine, blood urea nitrogen,
      and urate, and 11 healthy controls were examined. We measured excretory renal
      function parameters (urine volume, osmolarity, sodium, chloride, potassium,
      calcium, phosphate, microalbumin, aldosterone, creatinine) between 7:00 am and
      10:00 pm and between 10:00 pm and 7:00 am. RESULTS: During the nighttime, volume
      (P=0.006), sodium (P=0.009), and chloride excretion (P=0.001) were significantly
      higher, and osmolarity (P=0.025) was significantly lower in patients as compared
      to controls. In comparing daytime to nighttime, controls showed the physiological
      reduced nocturnal excretion of volume (P=0.009) and chloride (P=0.023), and an
      increased osmolarity (P=0.026), but patients showed similar excretion rates of
      these parameters (all differences ns). CONCLUSIONS: These data indicate a loss of
      normal circadian profile of urine excretion in iRLS. The elevated nighttime
      excretion, with values similar to those in the daytime, hint at a possibly
      elevated fluid, sodium, and chloride intake during daytime.

PMID- 16099718
TI  - Further evidence supporting the use of sodium oxybate for the treatment of
      cataplexy: a double-blind, placebo-controlled study in 228 patients.
AB  - BACKGROUND AND PURPOSE: To measure the effect of the nocturnal administration of
      sodium oxybate on cataplexy in patients with narcolepsy. PATIENTS AND METHODS:
      This trial was conducted with 228 adult narcolepsy/cataplexy patients in 42 sleep
      clinics. Patients using anticataplectic medications were weaned from these
      medications, then randomized to receive 4.5, 6 or 9 g sodium oxybate nightly or
      placebo for 8 weeks. Patients receiving 6 and 9 g doses were titrated to their
      final dose in weekly 1.5 g increments. Placebo patients underwent a randomized
      mock dose-titration schedule. The effect of sodium oxybate on weekly cataplexy
      attacks was measured using patient daily diaries. RESULTS: Compared to placebo,
      nightly doses of 4.5, 6 and 9 g sodium oxybate for 8 weeks resulted in
      statistically significant median decreases in weekly cataplexy attacks of 57.0,
      65.0 and 84.7%, respectively. The decrease in cataplexy at the 4.5 g dose
      represents a novel finding. The weekly increase in sodium oxybate dose was
      associated with fewer adverse events than previously reported in double-blind
      sodium oxybate trials using fixed doses. Some adverse events reported
      demonstrated a clear dose-response relationship. CONCLUSIONS: In the largest
      study of its kind, sodium oxybate was highly effective for the treatment of
      cataplexy. The improvements in cataplexy are dependent on the dosage of sodium
      oxybate as well on the duration of treatment. Weekly dose titration appears to be
      well-tolerated.

PMID- 16099719
TI  - Genetic susceptibility and immune-mediated destruction in beryllium-induced
      disease.
AB  - Chronic beryllium disease (CBD) is a hypersensitivity disorder caused by
      beryllium exposure in the workplace and is characterized by the accumulation of
      beryllium-specific CD4(+) T cells in the lung and granulomatous inflammation.
      This disorder occurs in 2-16% of exposed workers, depending on genetic
      susceptibility and the nature of the exposure. Susceptibility has been associated
      with HLA-DP alleles possessing a glutamic acid at the 69th position (Glu(69)) of
      the beta-chain. The mechanism for this association lies in the ability of these
      HLA-DP molecules to present beryllium to pathogenic CD4(+) T cells. These
      findings in CBD have important implications for studies in autoimmune diseases,
      including those in which the inciting antigen is unknown and the target organ is
      inaccessible.

PMID- 16099720
TI  - Chemokines, chemokine receptors and pain.
AB  - Many patients suffer from neuropathic pain as a result of injury to the
      peripheral nervous system (e.g. post-herpetic neuralgia or diabetic neuropathy)
      or to the central nervous system (e.g. spinal cord injury or stroke). The most
      distinctive symptom of neuropathic pain is allodynia, whereby normally non
      painful stimuli, such as light touch, become painful. Traditionally, inflammatory
      and neuropathic pain syndromes have been considered distinct entities; however,
      recent evidence belies this strict dichotomy. Nerve damage can stimulate
      macrophage infiltration and increase the number of activated T cells. Under these
      conditions, neuroinflammatory and immune responses contribute as much to the
      development and maintenance of pain as the initial damage itself. Recently,
      studies using animal models have shown that upregulation of chemokines is one of
      the mechanisms underlying the development and maintenance of chronic pain.

PMID- 16099721
TI  - Pacific collaboration to eliminate lymphatic filariasis.
AB  - A regional programme to combat lymphatic filariasis in the Pacific islands is
      showing great promise as it reaches its halfway point. The Pacific Programme to
      Eliminate Lymphatic Filariasis (PacELF), established in 1999, aims to eliminate
      the disease from the Pacific by 2010 - ten years ahead of the global target. Set
      up with support from Australia, and now funded primarily by Japan and underpinned
      by the Word Health Organization, PacELF is providing evidence that Pacific
      nations can work cooperatively to rid the region of one of its worst scourges, in
      addition to discovering techniques and new tools that should be of use in other
      regions.

PMID- 16099722
TI  - Plant active components - a resource for antiparasitic agents?
AB  - Plant essential oils (and/or active components) can be used as alternatives or
      adjuncts to current antiparasitic therapies. Garlic oil has broad-spectrum
      activity against Trypanosoma, Plasmodium, Giardia and Leishmania, and
      Cochlospermum planchonii and Croton cajucara oils specifically inhibit Plasmodium
      falciparum and Leishmania amazonensis, respectively. Some plant oils have
      immunomodulatory effects that could modify host-parasite immunobiology, and the
      lipid solubility of plant oils might offer alternative, transcutaneous delivery
      routes. The emergence of parasites resistant to current chemotherapies highlights
      the importance of plant essential oils as novel antiparasitic agents.

PMID- 16099723
TI  - Entamoeba: still more to be learned from the genome.

PMID- 16099724
TI  - Malaria parasites in mosquitoes: laboratory models, evolutionary temptation and
      the real world.
AB  - A recent study describing the effect of Plasmodium berghei infection on some
      Anopheles gambiae immune genes demonstrates that P. berghei is responsible for
      the upregulation of several genes involved in the immune response that affect
      parasitic development differently during the ookinete-to-oocyst developmental
      transition. It is important to question the relevance of such results, which are
      based on a laboratory model system, when discussing host-parasite interactions
      and, especially, the development of novel control strategies for malaria.

PMID- 16099725
TI  - Interpreting procedures from descriptive guidelines.
AB  - Errors in clinical practice guidelines may translate into errors in real-world
      clinical practice. The best way to eliminate these errors is to understand how
      they are generated, thus enabling the future development of methods to catch
      errors made in creating the guideline before publication. We examined the process
      by which a medical expert from the American College of Physicians (ACP) created
      clinical algorithms from narrative guidelines, as a case study. We studied this
      process by looking at intermediate versions produced during the algorithm
      creation. We identified and analyzed errors that were generated at each stage,
      categorized them using Knuth's classification scheme, and studied patterns of
      errors that were made over the set of algorithm versions that were created. We
      then assessed possible explanations for the sources of these errors and provided
      recommendations for reducing the number of errors, based on cognitive theory and
      on experience drawn from software engineering methodologies.

PMID- 16099726
TI  - Rac1 inhibition protects against hypoxia/reoxygenation-induced lipid peroxidation
      in human vascular endothelial cells.
AB  - Both in vivo models of ischemia/reperfusion and in vitro models of hypoxia
      (H)/reoxygenation (R) have demonstrated the crucial role of the Rac1-regulated
      NADPH oxidase in the production of injurious reactive oxygen species (ROS) by
      vascular endothelial cells (ECs). Since membrane lipid peroxidation has been
      established as one of the mechanisms leading to cell death, we examined lipid
      peroxidation in H/R-exposed cultured human umbilical vein ECs (HUVECs) and the
      role of Rac1 in this process. H (24 h at 1% O2)/R (5 min) caused an increase in
      intracellular ROS production compared to a normoxic control, as measured by
      dichlorofluorescin fluorescence. Nutrient deprivation (ND; 24 h), a component of
      H, was sufficient to induce a similar increase in ROS under normoxia. Either H(24
      h)/R (2 h) or ND (24 h) induced increases in lipid peroxidation of similar
      magnitude as measured by flow cytometry of diphenyl-1-pyrenylphosphine-loaded
      HUVECs and Western blotting analysis of 4-hydroxy-2-nonenal-modified proteins in
      cell lysates. In cells infected with a control adenovirus, H (24 h)/R (2 h) and
      ND (24 h) resulted in increases in NADPH-dependent superoxide production by 5-
      and 9-fold, respectively, as measured by lucigenin chemiluminescence. Infection
      of HUVECs with an adenovirus that encodes the dominant-negative allele of Rac1
      (Rac1N17) abolished these increases. Rac1N17 expression also suppressed the H/R-
      and ND-induced increases in lipid peroxidation. In conclusion, ROS generated via
      the Rac1-dependent pathway are major contributors to the H/R-induced lipid
      peroxidation in HUVECs, and ND is able to induce Rac1-dependent ROS production
      and lipid peroxidation of at least the same magnitude as H/R.

PMID- 16099727
TI  - Migraine: current concepts and emerging therapies.
AB  - Migraine is a recurrent incapacitating neurovascular disorder characterized by
      attacks of debilitating pain associated with photophobia, phonophobia, nausea and
      vomiting. Migraine affects a substantial fraction of world population and is a
      major cause of disability in the work place. Though the pathophysiology of
      migraine is still unclear three major theories proposed with regard to the
      mechanisms of migraine are vascular (due to cerebral vasodilatation),
      neurological (abnormal neurological firing which causes the spreading depression
      and migraine) and neurogenic dural inflammation (release of inflammatory
      neuropeptides). The modern understanding of the pathogenesis of migraine is based
      on the concept that it is a neurovascular disorder. The drugs used in the
      treatment of migraine either abolish the acute migraine headache or aim its
      prevention. The last decade has witnessed the advent of Sumatriptan and the
      'triptan' class of 5-HT1B/1D receptor agonists which have well established
      efficacy in treating migraine. Currently prophylactic treatments for migraine
      include calcium channel blockers, 5-HT2 receptor antagonists, beta adrenoceptor
      blockers and gamma-amino butyric acid (GABA) agonists. Unfortunately, many of
      these treatments are non specific and not always effective. Despite such
      progress, in view of the complexity of the etiology of migraine, it still remains
      undiagnosed and available therapies are underused. In this article, the diverse
      pieces of evidence that have linked the different theories of migraine with its
      pathophysiology are reviewed. Furthermore, the present therapeutic targets and
      futuristic approaches for the acute and prophylactic treatment of migraine, with
      a special emphasis to calcitonin gene-related peptide, are critically evaluated.

PMID- 16099728
TI  - Rudhira is a cytoplasmic WD40 protein expressed in mouse embryonic stem cells and
      during embryonic erythropoiesis.
AB  - We describe a novel murine gene rudhira that is expressed at high levels in
      embryonic stem cells and is restricted to blood islands and the erythroid lineage
      during embryonic development. Rudhira is expressed in angiogenic precursors but
      is excluded from the differentiated endothelium. Rudhira-expressing cells are
      seen in close proximity to endothelial cells in angiogenic blood vessels. Rudhira
      encodes a predicted cytoplasmic WD40 protein that is 98% identical to human
      BCAS3. The gene encoding BCAS3 maps to a breakpoint of hematological neoplasms on
      human chromosome 17q23, but its expression and function remain to be determined.
      We demonstrate that mouse Rudhira is a novel marker for analysis of the erythroid
      lineage.

PMID- 16099729
TI  - Very-KIND is a novel nervous system specific guanine nucleotide exchange factor
      for Ras GTPases.
AB  - The kinase non-catalytic c-lobe domain (KIND) evolved from the catalytic protein
      kinase fold into a potential protein interaction module for signalling proteins.
      Spir family actin organizers and the non-receptor phosphatase type 13 (PTP type
      13) encode a KIND domain in the very N-terminal parts of the proteins. Here we
      report the characterization and cloning of a third member of the KIND protein
      family, which we have named very-KIND (VKIND) because of its two KIND domains.
      Like the other members of the protein family, VKIND has a KIND domain at the N
      terminus. A second KIND domain is located in the central part of the protein. The
      C-terminal half encodes a guanine nucleotide exchange factor motif for Ras-like
      GTPases (RasGEF) and a RasGEF N-terminal module (RasGEFN). There is only one
      VKIND gene in the mammalian genomes and up to now we have found the gene only in
      vertebrates. During mouse embryogenesis the VKIND gene was specifically expressed
      in the developing nervous system. In adult mice Northern hybridizations revealed
      high expression only in brain. Low expression could be detected in ovary. In situ
      hybridizations showed a specific expression of VKIND in neuronal cells of the
      granular and Purkinje cell layers of the cerebellum.

PMID- 16099730
TI  - Bone geometry in response to long-term tennis playing and its relationship with
      muscle volume: a quantitative magnetic resonance imaging study in tennis players.
AB  - The benefit of impact-loading activity for bone strength depends on whether the
      additional bone mineral content (BMC) accrued at loaded sites is due to an
      increased bone size, volumetric bone mineral density (vBMD) or both. Using
      magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DXA), the
      aim of this study was to characterize the geometric changes of the dominant
      radius in response to long-term tennis playing and to assess the influence of
      muscle forces on bone tissue by investigating the muscle-bone relationship.
      Twenty tennis players (10 men and 10 women, mean age: 23.1+/-4.7 years, with
      14.3+/-3.4 years of playing) were recruited. The total bone volume, cortical
      volume, sub-cortical volume and muscle volume were measured at both distal radii
      by MRI. BMC was assessed by DXA and was divided by the total bone volume to
      derive vBMD. Grip strength was evaluated with a dynamometer. Significant side-to
      side differences (P<0.0001) were found in muscle volume (+9.7%), grip strength
      (+13.3%), BMC (+13.5%), total bone volume (+10.3%) and sub-cortical volume
      (+20.6%), but not in cortical volume (+2.6%, ns). The asymmetry in total bone
      volume explained 75% of the variance in BMC asymmetry (P<0.0001). vBMD was
      slightly higher on the dominant side (+3.3%, P<0.05). Grip strength and muscle
      volume correlated with all bone variables (except vBMD) on both sides (r=0.48
      0.86, P<0.05-0.0001) but the asymmetries in muscle parameters did not correlate
      with those in bone parameters. After adjustment for muscle volume or grip
      strength, BMC was still greater on the dominant side. This study showed that the
      greater BMC induced by long-term tennis playing at the dominant radius was
      associated to a marked increase in bone size and a slight improvement in
      volumetric BMD, thereby improving bone strength. In addition to the muscle
      contractions, other mechanical stimuli seemed to exert a direct effect on bone
      tissue, contributing to the specific bone response to tennis playing.

PMID- 16099731
TI  - Cardiac transplantation complicated by acute thrombotic occlusion of the right
      coronary artery.
AB  - We report the case of a 63-year-old male patient undergoing cardiac
      transplantation due to fourth time aortic valve endocarditis. The postoperative
      course was complicated by thrombotic occlusion of the right coronary artery (RCA)
      causing acute right ventricular myocardial infarction, which required
      extracorporeal membrane oxygenation. The RCA could be reopened by catheter-based
      intervention and the patient stabilized. In order to avoid further
      immobilization, a right ventricular assist device was implanted and an
      aortocoronary bypass to the RCA was performed. After that, the patient stabilized
      progressively, could be weaned from the assist device, and was discharged home 6
      weeks after transplantation. On coronary angiography, which is routinely
      performed 4 to 6 weeks after transplantation, a fistula from the RCA to the right
      ventricle was detected which was treated conservatively. Five months after
      transplantation, the patient is in good clinical condition without signs of
      recurrent endocarditis. This case shows that intense interdisciplinary
      cooperation of cardiac specialists allows the successful management of very
      complex patients in serious clinical conditions.

PMID- 16099732
TI  - Does preoperative multislice computed tomography predict operative times in total
      endoscopic coronary artery bypass grafting?
AB  - OBJECTIVE: Multislice computed tomography (MSCT) is currently discussed as a
      potential tool for procedure planning in endoscopic heart surgery. We aimed to
      assess the influence of various thoracic measurements on operative times in
      arrested heart totally endoscopic coronary artery bypass grafting (AHTECAB).
      METHODS: 34 patients (aged 59 years, 71% male) scheduled for AHTECAB were
      examined prospectively with ECG-gated 16-channel MSCT angiography of coronary
      arteries and internal mammary arteries. All AHTECABs were single LIMA to LAD
      bypass operations using the Da Vinci telemanipulator and the ESTECH remote access
      perfusion system. RESULTS: The LIMA-LAD distances were: I (at origin of the first
      diagonal branch) 4.3 cm (2.5-6.0), II (aortic valve level) 3.7 cm (1.1-6.4), III
      (mitral valve level) 2.9 cm (0.7-5.0), and IV (basis cordis) 2.3 cm (0.6-4.3).
      The anterioposterior thoracic diameter was 12.4 cm (8.9-15.6), and the transverse
      diameter was 24.9 cm (21.1-26.8). LIMA-LAD distances I (P = .025, r = .396) and
      III (P = .042, r = .356) significantly correlated with the anastomotic time.
      Increased rotation of the heart to the left was associated with a decreased
      cardiopulmonary bypass time (p = .016, r = -.451). CONCLUSION: These data suggest
      that MSCT has the potential to predict operative times in robotic AHTECAB.

PMID- 16099733
TI  - Markers for perioperative myocardial ischemia: what both interventional
      cardiologists and cardiac surgeons need to know.
AB  - All novel markers of myocardial ischemia (ischemia-modified albumin, choline,
      unbound free fatty acids) lack cardiac specificity. Therefore, for the specific
      detection of myocardial ischemia selective blood sampling from an inserted
      coronary sinus catheter is needed, which limits the applicability of these
      markers in most clinical routine settings. In addition, the superiority of these
      novel markers over the calculation of myocardial lactate production, the current
      criterion standard for the laboratory diagnosis of myocardial ischemia, has not
      been demonstrated so far, and even comparative data is frequently lacking.
      Further the superiority of these new candidate markers over lactate determination
      for the diagnosis of myocardial ischemia in peripherally drawn blood samples has
      not been demonstrated either, and these novel parameters appear not to be a
      breakthrough for laboratory diagnosis of myocardial ischemia during or after
      percutaneous coronary interventions or coronary artery bypass grafting. The
      determination of cardiac troponin I or troponin T is the current criterion
      standard for the laboratory diagnosis of myocardial damage due to their higher
      sensitivities and specificities compared to creatine kinase isoenzyme MB.
      According to current knowledge, troponin increases in peripherally drawn blood
      samples must be regarded as an indicator of myocardial necrosis which, however,
      may be limited, only detectable by troponin and may be missed by creatine kinase
      isoenzyme MB determination. After on-pump coronary artery bypass grafting the
      generally applied troponin discriminator limits are not valid as there is
      limited, inevitable cardiac tissue damage occurring during the surgical
      procedure. Therefore, troponins are significantly increased after reperfusion of
      the arrested heart over values seen before bypass and also in patients without
      complications. Perioperative myocardial infarctions can be reliably identified by
      their characteristic troponin time courses, and both peak concentrations and time
      of peak values are diagnostic criteria. Troponin release is lower in off-pump
      compared to on-pump bypass surgery. Despite the controversy over the significance
      of troponin elevations after clinically uncomplicated and successful procedures,
      it is tempting to postulate that less myocardial damage as detected by troponin
      release is beneficial for the patient. After elective percutaneous coronary
      interventions, only troponin increases >8-fold the upper reference limit were
      associated with increased mortality in long-term follow-up.

PMID- 16099734
TI  - The need of a hybrid approach for the treatment of atrial fibrillation.
AB  - Atrial fibrillation represents nowadays one of the most important burdens in the
      field of arrhythmia. Albeit often inadequate, medical treatment is still
      considered the "first-step" approach. Non-pharmacological strategies, either
      surgical or interventional, recently gained an increasing interest among both
      cardiac surgeons and electrophysiologists. From the surgical standpoint, the
      introduction of different energy sources and the development of minimally
      invasive techniques as an alternative to the original "cut-and-sew" technique
      allowed a new dawn in the surgical treatment of atrial fibrillation. In the
      meanwhile, electrophysiologists developed more complex ablation systems that
      allowed the creation of linear lesions, similar to the surgical ones, while
      mapping the atria with three-dimensional (3D) navigation systems. Nevertheless,
      the success rate in terms of sinus rhythm restoration was around 80%-85% in both
      fields. We foresee that the combination of the two approaches (i.e., surgical and
      percutaneous approach), in common hybrid approach, will allow a substantial
      reform for the definitive cure of atrial fibrillation, either paroxysmal or
      permanent, providing the highest success rates along with the best care for
      patients' health.

PMID- 16099735
TI  - Dose response curves for microwave ablation in the cardioplegia-arrested porcine
      heart.
AB  - INTRODUCTION: Microwave ablation has been used clinically for the surgical
      treatment of atrial fibrillation, particularly during valve procedures. However,
      dose- response curves have not been established for this surgical environment.
      The purpose of this study was to examine dosimetry curves for the Flex 4 and Flex
      10 microwave devices in an acute cardioplegia-arrested porcine model. METHODS:
      Twelve domestic pigs (40-45 kg) were acutely subjected to Flex 4 (n = 6) and Flex
      10 (n = 6) ablations. On a cardioplegically arrested heart maintained at 10
      15(o)C, six endocardial atrial and seven epicardial ventricular lesions were
      created in each animal. Ablations were performed for 15 s, 30 s, 45 s, 60 s, 90
      s, 120 s, and 150 s (65 W, 2.45 GHz). The tissue was stained with 2,3,5-triphenyl
      tetrazolium chloride and lesions were sectioned at 5 mm intervals. Lesion depth
      and width were determined from digital photomicrographs of each lesion
      (resolution +/- .03 mm). RESULTS: Average atrial thickness was 2.88 +/- .4 mm
      (range 1.0 to 8.0 mm). 94% of ablated atrial sections created by the FLEX 4 (n =
      16) and the FLEX 10 (n = 16) were transmural at 45 seconds. 100% of atrial
      sections were transmural at 90 seconds with the FLEX 10 (n = 14) and at 60
      seconds with the Flex 4 device (n = 15). Lesion width and depth increased with
      duration of application. CONCLUSION: Both devices were capable of producing
      transmural lesions on the cardioplegically arrested heart at 65 W. These curves
      will allow surgeons to ensure transmural ablation by tailoring energy delivery to
      the specific atrial geometry.

PMID- 16099736
TI  - Time and risk analysis for acute type A aortic dissection surgery performed by
      hypothermic circulatory arrest, cerebral perfusion, and open distal aortic
      anastomosis.
AB  - BACKGROUND: Hypothermic total circulatory arrest, retrograde or antegrade
      cerebral perfusion, and open distal anastomosis are important stages of surgical
      management and cerebral protection for acute type A dissections. Among the
      factors that influence survival are the transfer time to hospital from the onset
      of symptoms, in-hospital transfer time to operation, organ malperfusion,
      preoperative risk factors, and intraoperative variables. The aim of this study
      was to analyze time and risk factors during surgical management. METHODS: Between
      September 1996 and March 2002, a total of 26 patients with acute type A aortic
      dissection were operated. Sixteen patients (61.5%) were male and mean age was 49
      ( 13.1 years (range: 26-68). The diagnosis was based on clinical examination,
      telecardiography, transthoracic echocardiography, computerized tomography, and
      angiography. Hypothermic total circulatory arrest, retrograde or antegrade
      cerebral perfusion and open distal anastomosis were used during the procedures.
      Operative techniques were as follows: supracoronary ascending aortic replacement
      (17 patients), aortic root and ascending aortic replacement with flanged
      composite grafting technique (5 patients), replacement of ascending aorta and
      hemiarcus (1 patient), aortic root and ascending aortic replacement with modified
      Bentall technique (1 patient), replacement of ascending aorta and arcus (1
      patient), and total arcus replacement with elephant trunk technique and modified
      Bentall procedure (1 patient). RESULTS: The early postoperative mortality rate
      within the first 30 days was 26.9%, and the late postoperative mortality rate was
      15.8%. Two patients (7.7%) developed major neurological complications during the
      postoperative period. Time to admission, durations of total circulatory arrest,
      cross-clamp, cardiopulmonary bypass, and intubation were longer, and
      postoperative blood loss was greater in patients who died during early
      postoperative period, although the differences did not reach statistical
      significance. Duration of total circulatory arrest was longer in patients who
      developed neurological dysfunction compared to patients without this
      complication; this difference also did not reach statistical significance.
      CONCLUSIONS: Total circulatory arrest, cerebral perfusion, and open distal
      anastomosis are reliable options in the surgical management of acute type A
      aortic dissections. With open distal anastomosis aortic arcus can be evaluated,
      distal anastomosis can be performed more easily, and postoperative neurological
      recovery is hastened. In the present study, although statistical significance
      could not be reached due to limited sample size, the time to admission, durations
      of total circulatory arrest, cross-clamp, and cardiopulmonary bypass, and the
      amount of postoperative chest output seem to influence postoperative survival.

PMID- 16099737
TI  - Transplantation of autologous bone marrow-derived cells into the myocardium of
      patients undergoing coronary bypass.
AB  - BACKGROUND: Animal studies suggest that cell transplantation, including bone
      marrow-derived cells, can ameliorate left ventricular remodeling following
      myocardial ischemia. Clinical evaluation of the potential benefits of this
      approach is limited by the lack of safety and feasibility studies. We have
      assessed the safety and feasibility of intramyocardial transplantation of
      autologous bone marrow-derived cells in patients undergoing coronary artery
      bypass graft (CABG) surgery. METHODS AND RESULTS: Between December 2001 and May
      2002 7 patients, scheduled for CABG, consented to the trial. All had CABG using
      hypothermic cardiopulmonary bypass (CPB) and cold cardioplegic arrest. An average
      of 21 10(6) (8.6 10(6) to 35.1 10(6)) nucleated cells, and 4.2 10(4) (2.5 10(4)
      to 8.1 10(4)) CD34+ cells were injected into the anterior-lateral wall of the
      left ventricle, after discontinuation of cardiopulmonary bypass. The end points
      to assess safety included death, massive bleeding, electrocardiographic or
      biochemical evidence of myocardial infarction, ventricular dysrhythmia,
      myocardial perfusion, ventricular function, and the patients' functional status.
      All patients recovered well without ventricular arrhythmia, bleeding, or other
      major peri-operative complications. The average intensive care unit (ICU) and
      hospital stay was 1 and 7 days, respectively. Repeat Technetium-99m myocardial
      perfusion stress imaging and echocardiography 6 weeks after surgery showed
      improvement in tissue perfusion, and an average improvement of left ventricular
      function of 13.5% +/- 11.54% (the mean pre- and post-operative left ventricular
      EF were 32.5% +/- 15.46% and 46% +/- 18.55%, respectively). Twenty-four hours
      Holter monitoring showed no significant arrhythmia, 3 months post-operatively.
      All patients with narrow QRS complex showed no evidence of late potential, on
      signal-averaged electrocardiogram. At 4 to 9 months after surgery patients were
      in NYHA functional class "I". CONCLUSIONS: This early clinical experience shows
      that autologous bone marrow-derived cell transplantation into myocardium is
      feasible and relatively safe. Further clinical trials to assess the role of cell
      transplantation for myocardial repair are required.

PMID- 16099738
TI  - Triple coronary bypass in a child with homozygous familial hypercholesterolemia.
AB  - Here we report triple coronary bypass procedure in a 12-year-old girl with
      familial homozygous hypercholesterolemia and extensive coronary atherosclerosis.
      She had successful cardiopulmonary resuscitation at home by her father 4 months
      before the operation. Total cholesterol level was 1300 mg/dL initially without
      antilipidemic treatment. Extensive three vessel disease with right coronary
      proximal stenosis and left coronary ostial stenoses was determined by
      angiography. Left internal thoracic artery, left radial artery, and saphenous
      vein grafts were used for coronary revascularization. Saphenous vein graft to
      right posterior descending artery, radial artery graft to obtuse marginal artery,
      and LITA to left anterior descending artery anastomoses were performed
      consecutively. Ten months after the operation, she is in good condition under
      intensive antilipidemic therapy and weekly lipid apheresis.

PMID- 16099739
TI  - The preferable use of port access surgical technique for right and left atrial
      procedures.
AB  - We analyzed the results of mitral valve operations, either alone or in any
      combination with the tricuspid valve surgeries in the period from January 2001
      till June 2004. The period was divided into two parts, classical sternotomy part
      (C) (110 patients) and minimally invasive port access part (PA) (105 patients),
      later being used from December 2002 till now. Also, what we were interested in
      was the total hospital cost of both types of the procedures and if there are any
      advantages of port access over the classical sternotomy. The mean age was 61.2 +/
      10.2 and 60.3 +/- 12.4 (C versus PA) and mean additive Euroscore was 6.5 versus
      4.8 (C versus PA). There were statistically significant differences (P < .0001)
      in cardiopulmonary bypass time (CPB) and aortic cross-clamp time (AXT) between
      both groups: CPB C versus PA: 98.3 +/- 33.5 minutes versus 149.2 +/- 44.2 minutes
      (mean +/- sd), AXT C versus PA: 62.9 +/- 20.6 minutes versus 88.3 +/- 26.8
      minutes (mean +/- sd). There were no statistically significant differences in
      mortality and stroke for both the groups (mortality P = 1, stroke P = .53). There
      were statistically significant differences in favor of the port access over the
      classical one for: intensive unit stay (P = .004), postoperative stay in days (P
      < .0001), blood transfusion (P < .0001), postoperative thoracic bleeding (P <
      .0001), and extubation time in hours (P < .0001). Furthermore, costs analyses
      showed that the average total patient cost was less for port access (P < .0005).
      The differences between endo and classical type suggested that the port access
      type of surgery is 20% cheaper than the classical one. We may conclude that port
      access surgery is an acceptable alternative to classical type of surgery, also in
      complex pathology of the mitral and tricuspid valve.

PMID- 16099740
TI  - The use of suture anchors for sternal nonunion as a new technical approach
      (Demircin-Dogan technique).
AB  - OBJECTIVES: Various comparative studies and techniques have been described for
      median sternotomy closure in the literature, previously. However, some patients
      are still under risk of sternal dehiscence, malunion or nonunion due to intrinsic
      or extrinsic factors after median sternotomy closure. Sternal nonunion described
      as sternal pain, with clicking, instability, or both for more than 3 months in
      the absence of infection, is an uncommon complication of midline sternotomy
      incision. To date, only a few studies have addressed the entity of sternal
      nonunion and its treatment. MATERIAL AND METHOD: The suture anchor system has
      been described for the fixation of tendons or ligaments to the bone in the
      orthopedic, and then in cardiac surgery for closure of sternum. In the present
      study, we used different methods for correction and reduction of sternal nonunion
      with the use of suture anchors and it accompanied steel wires as an alternative
      technique in a male patient after coronary artery bypass grafting. RESULTS: There
      was no complication due to suture anchors. Sternal stability, reduction, and
      fixation were achieved successfully. CONCLUSION: Sternal nonunion and dehiscence
      may be the cause of prolonged hospitalization and increased mortality and
      morbidity if the patient is not treated surgically. This device may protect the
      wire from cutting into the sternal bone because the thoracal lateral enforcement
      may be decreased by the devices when the patient is breathing, and with upper
      extremity movement. This technique can be used easily, safely, and effectively in
      the repair of sternal nonunion.

PMID- 16099742
TI  - Scientific Grid computing.
AB  - We introduce a definition of Grid computing which is adhered to throughout this
      Theme Issue. We compare the evolution of the World Wide Web with current
      aspirations for Grid computing and indicate areas that need further research and
      development before a generally usable Grid infrastructure becomes available. We
      discuss work that has been done in order to make scientific Grid computing a
      viable proposition, including the building of Grids, middleware developments,
      computational steering and visualization. We review science that has been enabled
      by contemporary computational Grids, and associated progress made through the
      widening availability of high performance computing.

PMID- 16099743
TI  - Building the TeraGrid.
AB  - On 1 October 2004, the most ambitious high-performance Grid project in the United
      States-the TeraGrid-became fully operational. Resources at nine sites--the San
      Diego Supercomputer Center, the California Institute of Technology, the National
      Center for Supercomputing Applications, the University of Chicago/Argonne
      National Laboratory, Pittsburgh Supercomputing Center, Texas Advanced Computing
      Center, Purdue University, Indiana University and Oak Ridge National Laboratory
      were joined via an ultra-fast optical network, unified policies and security
      procedures and a sophisticated distributed computing software environment. Funded
      by the National Science Foundation, the TeraGrid enables scientists and engineers
      to combine distributed, multiple data sources with computation at any of the
      sites or link massively parallel computer simulations to extreme-resolution
      visualizations at remote sites. A single shared utility lets multiple resources
      be easily leveraged and provides improved access to advanced computational
      capabilities. One of the demonstrations of this new model for using distributed
      resources, Teragyroid, linked the infrastructure of the TeraGrid with computing
      resources in the United Kingdom via a transatlantic data fibre link. Once
      connected, the software framework of the RealityGrid project was used to
      successfully explore lattice-Boltzmann simulations involving lattices of over one
      billion sites.

PMID- 16099744
TI  - Building an infrastructure for scientific Grid computing: status and goals of the
      EGEE project.
AB  - The state of computer and networking technology today makes the seamless sharing
      of computing resources on an international or even global scale conceivable.
      Scientific computing Grids that integrate large, geographically distributed
      computer clusters and data storage facilities are being developed in several
      major projects around the world. This article reviews the status of one of these
      projects, Enabling Grids for E-SciencE, describing the scientific opportunities
      that such a Grid can provide, while illustrating the scale and complexity of the
      challenge involved in establishing a scientific infrastructure of this kind.

PMID- 16099745
TI  - The service architecture of the TeraGyroid experiment.
AB  - We describe the service architecture of the successful TeraGyroid experiment. In
      particular we discuss the use of the open Grid service infrastructure (OGSI) to
      build the services used during the experiment and illustrate the problems we
      encountered.

PMID- 16099746
TI  - Building messaging substrates for Web and Grid applications.
AB  - Grid application frameworks have increasingly aligned themselves with the
      developments in Web services. Web services are currently the most popular
      infrastructure based on service-oriented architecture (SOA) paradigm. There are
      three core areas within the SOA framework: (i) a set of capabilities that are
      remotely accessible, (ii) communications using messages and (iii) metadata
      pertaining to the aforementioned capabilities. In this paper, we focus on issues
      related to the messaging substrate hosting these services; we base these
      discussions on the NARADABROKERING system. We outline strategies to leverage
      capabilities available within the substrate without the need to make any changes
      to the service implementations themselves. We also identify the set of services
      needed to build Grids of Grids. Finally, we discuss another technology, HPSEARCH,
      which facilitates the administration of the substrate and the deployment of
      applications via a scripting interface. These issues have direct relevance to
      scientific Grid applications, which need to go beyond remote procedure calls in
      client-server interactions to support integrated distributed applications that
      couple databases, high performance computing codes and visualization codes.

PMID- 16099747
TI  - Reliable multicast for the Grid: a case study in experimental computer science.
AB  - In its simplest form, multicast communication is the process of sending data
      packets from a source to multiple destinations in the same logical multicast
      group. IP multicast allows the efficient transport of data through wide-area
      networks, and its potentially great value for the Grid has been highlighted
      recently by a number of research groups. In this paper, we focus on the use of IP
      multicast in Grid applications, which require high-throughput reliable multicast.
      These include Grid-enabled computational steering and collaborative visualization
      applications, and wide-area distributed computing. We describe the results of our
      extensive evaluation studies of state-of-the-art reliable-multicast protocols,
      which were performed on the UK's high-speed academic networks. Based on these
      studies, we examine the ability of current reliable multicast technology to meet
      the Grid's requirements and discuss future directions.

PMID- 16099748
TI  - Towards performance control on the Grid.
AB  - Advances in computational Grid technologies are enabling the development of
      simulations of complex biological and physical systems. Such simulations can be
      assembled from separate components--separately deployable computation units of
      well-defined functionality. Such an assemblage can represent an application
      composed of interacting simulations or might comprise multiple instances of a
      simulation executing together, each running with different simulation parameters.
      However, such assemblages need the ability to cope with heterogeneous and
      dynamically changing execution environments, particularly where such changes can
      affect performance. This paper describes the design and implementation of a
      prototype performance control system (PerCo), which is capable of monitoring the
      progress of simulations and redeploying them so as to optimize performance. The
      ability to control performance by redeployment is demonstrated using an
      assemblage of lattice Boltzmann simulations running with and without control
      policies. The cost of using PerCo is evaluated and it is shown that PerCo is able
      to reduce overall execution time.

PMID- 16099749
TI  - WEDS: a Web services-based environment for distributed simulation.
AB  - Web services have the potential to radically enhance the ability of researchers
      to make use of distributed computing resources, but jargon and a plethora of
      standards make their use almost impossible for the scientist without prior
      experience of the necessary technologies. A powerful and simple WSRF-based
      middleware scheme is presented, designed to let scientists remotely deploy single
      or multiple instances of a pre-existing code across multiple resources, and
      giving steering, visualization and workflow functionality with only simple
      modifications to program code. It is hoped that the development and
      implementation of such a toolkit will be relevant not only to the problem of
      deploying workstation-class codes in real time, but also the move towards more
      tractable alternatives to the Globus toolkit for deployment of processes in a
      high-performance computing environment.

PMID- 16099750
TI  - RealityGrid: an integrated approach to middleware through ICENI.
AB  - The advancement of modelling and simulation within complex scientific
      applications is currently constrained by the rate at which knowledge can be
      extracted from the data produced. As Grid computing evolves, new means of
      increasing the efficiency of data analysis are being explored. RealityGrid aims
      to enable more efficient use of scientific computing resources within the
      condensed matter, materials and biological science communities. The Imperial
      College e-Science Networked Infrastructure (ICENI) Grid middleware provides an
      end-to-end pipeline that simplifies the stages of computation, simulation and
      collaboration. The intention of this work is to allow all scientists to have
      access to these features without the need for heroic efforts that have been
      associated with this sort of work in the past. Scientists can utilise advanced
      scheduling mechanisms to ensure efficient planning of computations, visualize and
      interactively steer simulations and securely collaborate with colleagues via the
      Access Grid through a single integrated middleware application.

PMID- 16099751
TI  - Towards a Grid infrastructure to support integrative approaches to biological
      research.
AB  - This paper discusses the scientific rationale behind the e-Science project,
      Integrative Biology, which is developing mathematical modelling tools, HPC
      enabled simulations and an underpinning Grid infrastructure to provide an
      integrative approach to the modelling of complex biological systems. The project
      is focusing on two key applications to validate the approach: the modelling of
      heart disease and cancer, which together are responsible for over 60% of deaths
      in the United Kingdom. This paper provides an overview of the project, describes
      the initial prototype architecture and discusses the long-term scientific aims.

PMID- 16099752
TI  - A practical toolkit for computational steering.
AB  - Computational steering refers to the real-time interaction of a scientist with
      their running simulation code. Despite the many benefits associated with
      computational steering, its uptake to date has been limited. In this paper we
      discuss the reasons for this and how the computational steering library and
      associated tools developed as part of the RealityGrid project aim to tackle them.
      We describe the functionality of the steering library and the use of Grid
      services in constructing a generic, dynamic architecture for discovering,
      steering and connecting visualization software to running simulations. The use of
      on-line visualization for providing feedback to the scientist is described,
      including the ways in which it may be enhanced through tools such as Chromium and
      Access Grid. Finally, we illustrate the flexibility of our approach by describing
      the functionality that has been added to various simulation codes as part of the
      RealityGrid project.

PMID- 16099753
TI  - Steering UNICORE applications with VISIT.
AB  - The UNICORE (UNiform Interface to COmputing REsources) software provides a Grid
      infrastructure together with a computing portal for engineers and scientists to
      access supercomputer centres from anywhere on the Internet. While UNICORE is
      primarily designed for the submission and control of batch jobs, it is also
      feasible to establish an on-line connection between an application and the
      UNICORE user-client. This opens up the possibility of performing on-line
      visualization and computational steering of applications under UNICORE control
      while maintaining the security provided by this system. This contribution
      describes the design of a steering extension to UNICORE based on the steering
      toolkit VISIT (VISualization Interface Toolkit). VISIT is a lightweight library
      that supports bidirectional data exchange between visualizations and parallel
      applications. As an example application, a parallel simulation of a laser-plasma
      interaction that can be steered by an AVS/Express application is presented.

PMID- 16099754
TI  - Improving scientists' interaction with complex computational-visualization
      environments based on a distributed grid infrastructure.
AB  - The grid has the potential to transform collaborative scientific investigations
      through the use of closely coupled computational and visualization resources,
      which may be geographically distributed, in order to harness greater power than
      is available at a single site. Scientific applications to benefit from the grid
      include visualization, computational science, environmental modelling and medical
      imaging. Unfortunately, the diversity, scale and location of the required
      resources can present a dilemma for the scientific worker because of the
      complexity of the underlying technology. As the scale of the scientific problem
      under investigation increases so does the nature of the scientist's interaction
      with the supporting infrastructure. The increased distribution of people and
      resources within a grid-based environment can make resource sharing and
      collaborative interaction a critical factor to their success. Unless the
      technological barriers affecting user accessibility are reduced, there is a
      danger that the only scientists to benefit will be those with reasonably high
      levels of computer literacy. This paper examines a number of important human
      factors of user interaction with the grid and expresses this in the context of
      the science undertaken by RealityGrid, a project funded by the UK e-Science
      programme. Critical user interaction issues will also be highlighted by comparing
      grid computational steering with supervisory control systems for local and remote
      access to the scientific environment. Finally, implications for future grid
      developers will be discussed with a particular emphasis on how to improve the
      scientists' access to what will be an increasingly important resource.

PMID- 16099755
TI  - A grid-enabled lightweight computational steering client: a .NET PDA
      implementation.
AB  - The grid has been developed to support large-scale computer simulations in a
      diverse range of scientific and engineering fields. Consequently, the increasing
      availability of powerful distributed computing resources is changing how
      scientists undertake large-scale modelling/simulation. Instead of being limited
      to local computing resources, scientists are now able to make use of
      supercomputing facilities around the world. These grid resources comprise
      specialized distributed three-dimensional visualization environments through to
      massive computational systems. The scientist usually accesses these resources
      from reasonably high-end desktop computers. Even though most modern desktop
      computers are provided with reasonably powerful three-dimensional graphical
      hardware, not all scientific applications require high-end three-dimensional
      visualization because the data of interest is essentially numerical or two
      dimensional graphical data. For these applications, a much simpler two
      dimensional graphical displays can be used. Since large jobs can take many hours
      to complete the scientist needs access to a technology that will allow them to
      still monitor and control their job while away from their desks. This paper
      describes an effective method of monitoring and controlling a set of chained
      computer simulations by means of a lightweight steering client based on a small
      personal digital assistant (PDA). The concept of using a PDA to steer a series of
      computational jobs across a supercomputing resource may seem strange at first but
      when scientists realize they can use these devices to connect to their
      computation wherever there is a wireless network (or cellular phone network) the
      concept becomes very compelling. Apart from providing a much needed easy-to-use
      interface, the PDA-based steering client has the benefit of freeing the scientist
      from the desktop. It is during this monitoring stage that the hand-held PDA
      client is of particular value as it gives the application scientist greater
      freedom to leave his or her desk but still communicate with their simulation,
      with the proviso that they remain within the range of a wireless network.

PMID- 16099756
TI  - Large-scale lattice Boltzmann simulations of complex fluids: advances through the
      advent of computational Grids.
AB  - During the last 2.5 years, the RealityGrid project has allowed us to be one of
      the few scientific groups involved in the development of computational Grids.
      Since smoothly working production Grids are not yet available, we have been able
      to substantially influence the direction of software and Grid deployment within
      the project. In this paper, we review our results from large-scale three
      dimensional lattice Boltzmann simulations performed over the last 2.5 years. We
      describe how the proactive use of computational steering, and advanced job
      migration and visualization techniques enabled us to do our scientific work more
      efficiently. The projects reported on in this paper are studies of complex fluid
      flows under shear or in porous media, as well as large-scale parameter searches,
      and studies of the self-organization of liquid cubic mesophases.

PMID- 16099757
TI  - Physical and computational scaling issues in lattice Boltzmann simulations of
      binary fluid mixtures.
AB  - We describe some scaling issues that arise when using lattice Boltzmann (LB)
      methods to simulate binary fluid mixtures--both in the presence and absence of
      colloidal particles. Two types of scaling problem arise: physical and
      computational. Physical scaling concerns how to relate simulation parameters to
      those of the real world. To do this effectively requires careful physics, because
      (in common with other methods) LB cannot fully resolve the hierarchy of length,
      energy and time-scales that arise in typical flows of complex fluids. Care is
      needed in deciding what physics to resolve and what to leave unresolved,
      particularly when colloidal particles are present in one or both of two fluid
      phases. This influences steering of simulation parameters such as fluid viscosity
      and interfacial tension. When the physics is anisotropic (for example, in systems
      under shear) careful adaptation of the geometry of the simulation box may be
      needed; an example of this, relating to our study of the effect of colloidal
      particles on the Rayleigh-Plateau instability of a fluid cylinder, is described.
      The second and closely related set of scaling issues are computational in nature:
      how do you scale-up simulations to very large lattice sizes? The problem is acute
      for systems undergoing shear flow. Here one requires a set of blockwise co-moving
      frames to the fluid, each connected to the next by a Lees-Edwards like boundary
      condition. These matching planes lead to small numerical errors whose cumulative
      effects can become severe; strategies for minimizing such effects are discussed.

PMID- 16099758
TI  - Vortex core identification in viscous hydrodynamics.
AB  - We describe a software package designed for the investigation of topological
      fluid dynamics with a novel algorithm for locating and tracking vortex cores. The
      package is equipped with modules for generating desired vortex knots and links
      and evolving them according to the Navier-Stokes equations, while tracking and
      visualizing them. The package is parallelized using a message passing interface
      for a multiprocessor environment and makes use of a computational steering
      library for dynamic user intervention.

PMID- 16099759
TI  - Molecular dynamics simulations of nanoindentation and nanotribology.
AB  - We present results of parallel molecular dynamics simulations of nanoindentation
      and nanotribology experiments. The models we have developed describe both the
      sample and the indenter atomistically and model the effect of the cantilevers in
      an atomic force microscope through the use of springs. We show that the
      simulations are in good qualitative agreement with experiment and help to
      elucidate many of the mechanisms that take place during these processes. In
      particular, we illustrate the role that dislocations play both in nanoindentation
      and also in stick-slip. Further to this we show how real-time visualization and
      computational steering have been employed in these simulations to capture the
      dynamical events that take place.

PMID- 16099760
TI  - Computational steering in Monte Carlo simulations of thin film polystyrene.
AB  - High molecular weight polymer systems show very long relaxation times, of the
      order of milliseconds or more. This time-scale proves practically inaccessible
      for atomic-scale dynamical simulation such as molecular dynamics. Even with a
      Monte Carlo (MC) simulation, the generation of statistically independent
      configurations is non-trivial. Many moves have been proposed to enhance the
      efficiency of MC simulation of polymers. Each is described by a proposal density
      Q(x'; x): the probability of selecting the trial state x' given that the system
      is in the current state x. This proposal density must be parametrized for a
      particular chain length, chemistry and temperature. Choosing the correct set of
      parameters can greatly increase the rate at which the system explores its
      configuration space. Computational steering (CS) provides a new methodology for a
      systematic search to optimize the proposal densities for individual moves, and to
      combine groups of moves to greatly improve the equilibration of a model polymer
      system. We show that monitoring the correlation time of the system is an ideal
      single parameter for characterizing the efficiency of a proposal density
      function, and that this is best evaluated by a distributed network of replicas of
      the system, with the operator making decisions based on the averages generated
      over these replicas. We have developed an MC code for simulating an anisotropic
      atomistic bead model which implements the CS paradigm. We report simulations of
      thin film polystyrene.

PMID- 16099761
TI  - Hybrid molecular-continuum fluid models: implementation within a general coupling
      framework.
AB  - Over the past three years we have been developing a new approach for the
      modelling and simulation of complex fluids. This approach is based on a
      multiscale hybrid scheme, in which two or more contiguous subdomains are
      dynamically coupled together. One subdomain is described by molecular dynamics
      while the other is described by continuum fluid dynamics; such coupled models are
      of considerable importance for the study of fluid dynamics problems in which only
      a restricted aspect requires a fully molecular representation. Our model is
      representative of the generic set of coupled models whose algorithmic structure
      presents interesting opportunities for deployment on a range of architectures
      including computational grids. Here we describe the implementation of our
      HybridMD code within a coupling framework that facilitates flexible deployment on
      such architectures.

PMID- 16099762
TI  - On the performance of molecular dynamics applications on current high-end
      systems.
AB  - The effective exploitation of current high performance computing (HPC) platforms
      in molecular simulation relies on the ability of the present generation of
      parallel molecular dynamics code to make effective utilisation of these platforms
      and their components, including CPUs and memory. In this paper, we investigate
      the efficiency and scaling of a series of popular molecular dynamics codes on the
      UK's national HPC resources, an IBM p690+ cluster and an SGI Altix 3700. Focusing
      primarily on the AMBER, DL_POLY and NAMD simulation codes, we demonstrate the
      major performance and scalability advantages that arise through a distributed,
      rather than a replicated data approach.

PMID- 16099763
TI  - Grid-based steered thermodynamic integration accelerates the calculation of
      binding free energies.
AB  - The calculation of binding free energies is important in many condensed matter
      problems. Although formally exact computational methods have the potential to
      complement, add to, and even compete with experimental approaches, they are
      difficult to use and extremely time consuming. We describe a Grid-based approach
      for the calculation of relative binding free energies, which we call Steered
      Thermodynamic Integration calculations using Molecular Dynamics (STIMD), and its
      application to Src homology 2 (SH2) protein cell signalling domains. We show that
      the time taken to compute free energy differences using thermodynamic integration
      can be significantly reduced: potentially from weeks or months to days of wall
      clock time. To be able to perform such accelerated calculations requires the
      ability to both run concurrently and control in realtime several parallel
      simulations on a computational Grid. We describe how the RealityGrid
      computational steering system, in conjunction with a scalable classical MD code,
      can be used to dramatically reduce the time to achieve a result. This is
      necessary to improve the adoption of this technique and further allows more
      detailed investigations into the accuracy and precision of thermodynamic
      integration. Initial results for the Src SH2 system are presented and compared to
      a reported experimental value. Finally, we discuss the significance of our
      approach.

PMID- 16099764
TI  - Grid computing and biomolecular simulation.
AB  - Biomolecular computer simulations are now widely used not only in an academic
      setting to understand the fundamental role of molecular dynamics on biological
      function, but also in the industrial context to assist in drug design. In this
      paper, two applications of Grid computing to this area will be outlined. The
      first, involving the coupling of distributed computing resources to dedicated
      Beowulf clusters, is targeted at simulating protein conformational change using
      the Replica Exchange methodology. In the second, the rationale and design of a
      database of biomolecular simulation trajectories is described. Both applications
      illustrate the increasingly important role modern computational methods are
      playing in the life sciences.

PMID- 16099765
TI  - Peptide recognition by the T cell receptor: comparison of binding free energies
      from thermodynamic integration, Poisson-Boltzmann and linear interaction energy
      approximations.
AB  - The binding to the T cell receptor of wild-type and variant HTLV-1 Tax peptide
      complexed to the major histocompatibility complex has been investigated by means
      of molecular dynamics simulations. The binding free energy difference is
      calculated using the molecular mechanics Poisson-Boltzmann surface area and
      linear interaction energy methods. These methods extract useful information on
      the binding energetics from simulations of the physical states of the ligands,
      which are more computationally expedient than the commonly used thermodynamic
      integration method. The successful reproduction of the relative binding free
      energies shows that these methods can be useful for free energy calculations and
      the rational design of drugs and vaccines.

PMID- 16099766
TI  - Large scale molecular dynamics simulation of native and mutant dihydropteroate
      synthase-sulphanilamide complexes suggests the molecular basis for
      dihydropteroate synthase drug resistance.
AB  - Antibiotic resistance is hampering the efficacy of drugs in the treatment of
      several pathological infections. Dihydropteroate synthase (DHPS) has been
      targeted by sulphonamide inhibitors for the past 60 years and has developed
      different amino acid mutations to survive sulpha drug action. We couple homology
      modelling techniques and massively parallel molecular dynamics simulations to
      study both the drug-bound and apo forms of native and mutant DHPS. Simulations of
      the complex between sulphanilamide and Streptomyces pneumoniae, DHPS shows how
      sulphanilamide is able to position itself close to 6-hydroxymethyl-7, 8
      dihydropteridine-phosphate in a suitable position for the enzymatic
      transformation whereas in the mutant complex the sulpha drug is expelled from the
      catalytic site. Our simulations, therefore, provide insight into the molecular
      basis for drug resistance with S. pneumoniae DHPS.

PMID- 16099767
TI  - Grid-based dynamic electronic publication: a case study using combined experiment
      and simulation studies of crown ethers at the air/water interface.
AB  - Conventional paper-based scientific publications are limited in the amount of
      data and interaction they can provide. Simply placing an electronic copy of such
      a publication on the web makes for easier distribution, but more can be achieved
      by making use of the technology to navigate through the paper, to show the links
      between calculated parameters and the data, and provide access to the chain of
      calculated results all the way back to the raw data and ultimately the laboratory
      notebook. While the paper version of this publication is in a relatively
      conventional form, an interactive demonstrator version (available at
      http://epaper.combe.chem.soton.ac.uk and as an installable package) illustrates
      the concepts of publication@source, whereby all the figures and data presented in
      the paper are linked back to the original raw data together with a description of
      the processes by which the raw data were analysed. This level of interactivity is
      achieved using semantic technologies, which have the additional advantage of
      making the final document subsequently available and navigable by automated
      techniques. We present the combined information from experimental studies of
      surface tension and second harmonic generation (SHG) on the behaviour of benzo-15
      crown-5 at the solution/air interface, together with a molecular dynamics
      computer simulation, to demonstrate how the simulation aids the interpretation of
      the SHG experiment. The adsorption isotherm was determined using SHG and fitted
      to a Langmuir isotherm giving Delta ads G0=26 kJ mol-1.

PMID- 16099768
TI  - Prevention of viral hepatitis in the Nordic countries and Germany.
AB  - The Viral Hepatitis Prevention Board (VHPB) convened a meeting of international
      experts from the public and private sectors in the Nordic countries and Germany,
      in order to review the epidemiological situation, the surveillance systems for
      infectious diseases, the immunization programmes and policy, and the monitoring
      of adverse events after hepatitis vaccination in those countries, to evaluate
      prevention and control measures, and to identify the issues that arose and the
      lessons learnt. Considerable progress has been made in the past decades in the
      prevention and control of viral hepatitis in the respective countries.
      Vaccination programmes have been set up, blood products' safety has significantly
      been improved, and outbreak investigations remain the basis for the
      implementation of control measures. However, additional work remains to be done.
      Awareness of viral hepatitis among the public and professionals should further be
      raised, and more political support is needed regarding the value of prevention
      efforts and vaccination programmes.

PMID- 16099769
TI  - Cytokine levels in Chandipura virus associated encephalopathy in children.
AB  - An association of Chandipura (CHP) virus with an explosive outbreak of
      encephalitis in children from India affecting 349 children with 55% mortality was
      recently reported. To understand the role of cytokines in the pathogenesis of CHP
      infection, 14 paediatric encephalitis cases admitted to a tertiary care hospital
      and 5 age-matched apparently healthy control children were studied. At the time
      of sampling, post onset of disease was < or =2 d (Group A, n = 4) and >2 d (Group
      B, n = 10). Concentrations of IL-2, IFN-gamma, TNF-alpha and IL-6 in mitogen
      stimulated PBMC supernatants of patients and controls were assessed by ELISA. IL
      2 levels in Group A and B were significantly higher compared with controls
      (28.4+/-21.9 vs <7.8, p=0.01, 269.4+/-311.0.vs <7.8, p = 0.01). IFN-gamma levels
      were significantly elevated in both the groups compared with controls (394.4+/
      107.7 vs 13.9+/-20.9, p = 0.01, 339.5+/-244.9 vs 13.9+/-20.9, p = 0.01). TNF
      alpha and IL-6 levels were significantly higher in Group B compared with controls
      (573.1+/-472.5 vs 113.4.+/-148.3, p = 0.01, 486.2+/-145.7 vs 113.8+/-82.4, p =
      0.003). Cytokine levels were not significantly different in Groups A and B.

PMID- 16099770
TI  - The value of increased neopterin levels in reducing transfusion-transmitted virus
      infections: detection of a donation from a HBsAg positive chronic carrier by
      screening of neopterin in Turkish blood donors.
AB  - Neopterin is an early, sensitive and non-specific marker of cellular immunity. In
      the present study, serum levels of neopterin were measured by ELISA in 2760
      volunteer blood donors, all negative by routine screening tests. Neopterin
      concentrations ranged from 0.001 to 62.1 nmol/l. 141 donors (5.1%) were found to
      have high (> or =11 nmol/l) neopterin levels, and 57 of them accepted further
      investigations within about 3 weeks after their donation. Six had clinical
      symptoms, and 7 were positive for viral markers. Retesting of neopterin revealed
      that 2 of 57 donors still showed elevated results, who were adenovirus IgM and
      HBsAg positive donors, respectively. The present detection of a HBsAg positive
      donor who yielded negative result initially and a patient with adenovirus
      infection indicates that routine screening of neopterin levels in blood banks may
      reduce the risk for viral transmission.

PMID- 16099771
TI  - Giant myoepithelioma of the upper lip.
AB  - Myoepithelioma is a relatively rare form of salivary gland tumor composed
      entirely of myoepithelial cells. This tumor was formerly considered to be a
      subtype of pleomorphic adenoma; however, in the latest World Health Organization
      classification of 1991 it is listed as an independent entity. We report herein an
      extremely rare case of myoepithelioma of the upper lip. A 78-year-old Japanese
      female presented with a huge, painless mass on her upper lip. CT and MRI revealed
      a 50 x 40 mm(2) well-defined ovoid tumor. A benign minor salivary gland tumor was
      clinically suspected, and the patient underwent complete resection of the tumor
      under general anesthesia. The surgical defect was immediately reconstructed using
      an Abbe-Estlander flap. The tumor was histopathologically diagnosed as a benign
      myoepithelioma of the minor salivary gland. Immunohistochemically, the tumor
      cells were positive for vimentin, cytokeratins, alpha-smooth muscle actin and S
      100 protein, confirming the morphological diagnosis of myoepithelioma. The
      patient's postoperative clinical course was uneventful, and satisfactory results
      were obtained both functionally and esthetically. The pathology, clinical
      manifestations and treatment of myoepithelioma are reviewed.

PMID- 16099772
TI  - Activity patterns and time allocation during pregnancy: a longitudinal study of
      British women.
AB  - OBJECTIVE: Few studies provide data regarding the integrated everyday activities
      of Western pregnant women. The study aimed to quantify changes in the daily
      activity of women during pregnancy and to examine whether pregnancy has a
      differential impact on different activity domains. DESIGN: A prospective,
      longitudinal study of maternal time allocation and activity was carried out.
      METHODS: The time allocation patterns of 57 healthy nulliparous pregnant women
      were assessed at 16, 25, 34 and 38 weeks gestation by semi-structured interview.
      Mean total daily activity levels (DALs) were estimated according to the intensity
      and duration of each activity reported. Self-reported activity was sub-divided
      into occupational, recreational, domestic and nocturnal activity ratios. RESULTS:
      From 16 to 34 weeks gestation mean self-reported DAL declined significantly from
      1.54 to 1.40 METS (Metabolic Equivalent TEE Score, where TEE is total energy
      expenditure) (p < 0.001). In the different activity domains, mean occupational
      activity ratio decreased (p < 0.002) whilst nocturnal activity ratio increased (p
      < 0.002) from 16 to 34 weeks. Mean recreational activity ratio decreased
      significantly between 25 and 38 weeks (p < 0.001) but no significant changes were
      observed in mean domestic activity ratio. CONCLUSIONS: Low-risk pregnancy has a
      differential impact on occupational, recreational and domestic domains. Economies
      in energy expenditure appear to be made in occupational and recreational activity
      while domestic activities are largely maintained during pregnancy. Changes in
      physical activity may be influenced more by the type of activity rather than the
      intensity of activity.

PMID- 16099773
TI  - Growth patterns and secular trends over four decades in the dynamics of height
      growth of Indian boys and girls in Sri Aurobindo Ashram: a cohort study.
AB  - BACKGROUND: Growth parameters are widely used in the assessment of health,
      nutrition and physical characteristics of a population; however, there still
      exist uncertainties regarding ethnic variation and the influence of physical
      activity on growth. Due to the paucity of longitudinal data, the dynamics of the
      adolescent growth spurt have not been satisfactorily examined in most
      populations. AIM: The main purpose of this longitudinal study is to present the
      secular trends in the dynamics of height growth over four decades. In the
      process, this paper also aims to establish current norms for some biological
      parameters of growth and to address issues concerning ethnic variation and the
      effect of childhood physical activity on growth. METHODOLOGY: Three hundred and
      one boys and 235 girls of Indian origin who had been enrolled in the Sri
      Aurobindo International Centre of Education (SAICE) by age 6 and remained for at
      least 3 uninterrupted years were divided into four birth cohort periods. Cross
      sectional and longitudinal analyses were carried out to derive distance, velocity
      and acceleration curves. RESULTS: No significant differences were found between
      ethnic groups in any of the growth parameters. Over the 40-year span of this
      study, SAICE children prove to be taller than their Indian peers. A significant
      positive secular trend was seen in the height attained at all velocity turning
      points over the first two decades. Most pre-pubertal growth parameters in these
      children resemble those from developed nations. CONCLUSIONS: Children from most
      parts of India have similar genetic growth potential. After a significant
      positive secular trend in height attained over the first 20 years, the adult
      height has now plateaued. The significant difference in post-pubertal stature
      between the current generation and those of European origin indicates a genetic
      difference. Regular and graded physical activities have a salutary effect on
      growth. The data provide norms for healthy, active Indian child growing up in a
      satisfactory environment.

PMID- 16099774
TI  - Short-term changes in sedentary behaviour during adolescence: Project STIL
      (Sedentary Teenagers and Inactive Lifestyles).
AB  - HYPOTHESIS: Changes in body composition and body image during puberty will impact
      on sedentary behavioural choices. AIM: The study aimed to investigate the effects
      of changes in pubertal status, body composition and body image on changes in time
      spent being sedentary. PARTICIPANTS AND METHODS: Eighty-three school students
      aged 10-15 years were studied at 6-month intervals. BMI and percentage body fat
      (%BF) were calculated from anthropometric measures. Sedentary behaviour and sleep
      time were computed for weekday and weekend days using momentary-time-sampling
      diaries. Body image was measured using the Physical Self-Perception Profile for
      Children. Pubertal status was assessed from self-reported secondary sexual
      characteristics. RESULTS: During weekdays, boys' sedentary behaviour increased by
      a significantly greater amount for those who increased pubertal level compared
      with those who did not. No significant correlations were found between changing
      pubertal status, body composition, and body image for either gender. For girls,
      but not boys, a significant amount of the variance of the change in weekend day
      sedentary behaviour was explained by changing %BF, independent of changing
      pubertal status. CONCLUSION: Only a part of the hypothesis was supported by these
      data. Changes in sedentary behaviour were not associated with behavioural choices
      triggered by body compositional changes.

PMID- 16099775
TI  - The growth pattern of 0-1-year-old Danish children, when screened by public
      health nurses--the Copenhagen County Child Cohort 2000.
AB  - BACKGROUND: Using inadequate growth references when screening child health could
      lead to false conclusions concerning individual growth. We were concerned that
      this might apply to the official Danish growth reference. AIM: The study aimed to
      describe the current growth pattern of 0-1-year-old children in Denmark and
      compare it with national and international references, especially concerning
      differences that might cause misclassification regarding growth. SUBJECTS AND
      METHODS: The study population comprised the Copenhagen County Child Cohort 2000
      (CCCC2000) birth cohort, which consisted of 6090 children born during the year
      2000. Weight and length measurements were obtained from the National Birth
      Registry and from standardized records of public health nurses. Anthropometric
      measurements were available from 99% of the birth cohort. Growth curves were
      constructed using Cole's LMS method. The curves were compared with Danish and
      international references, including the NCHS, the CDC and the Euro Growth
      references. RESULTS: The CCCC2000 curves differed from all the chosen references.
      The CCCC2000 children were heavier and longer and with a substantially higher
      weight-for-age gain between 1 and 6 months. Shape-wise, the CCCC2000 weight
      curves resemble the new Euro Growth reference. CONCLUSIONS: The degree of
      differences concerning weight curves is large enough to cause misclassification
      and there seems to be a need for updated growth curves concerning infancy.

PMID- 16099776
TI  - RUS skeletal maturity of children in Beijing.
AB  - BACKGROUND: RUS (radius-ulna-short bones) maturity of children has been estimated
      in two provinces in China, but not in the capital. In order to obtain a clearer
      picture of skeletal maturity in China, it is indispensable to include children
      from Beijing in the study. AIM: The aims of this study were three-fold: (1) to
      establish RUS skeletal maturity of children in Beijing, (2) to compare RUS
      skeletal maturity in Beijing with the Tanner-Whitehouse 3 (TW3) standard and the
      Tokyo standard, and (3) to examine regional variation in skeletal maturity in
      China. METHODS: Hand and wrist radiographs of 631 boys and 642 girls, aged 6-18,
      were obtained in Beijing in 1997, and their RUS skeletal maturity was estimated
      using the TW3 method. RESULTS: RUS maturity of the Beijing children was very
      similar to the TW3 standard until the age of 10 years in the girls, and the age
      of 12 years in the boys. The girls attained full maturity at 15 years of age,
      matching the TW3 and Tokyo standards, while the boys reached full maturity at the
      age of 16 years, as in Tokyo boys, but 1 year earlier than the TW3 standards.
      Beijing children showed progressively more rapid bone maturation than the Harbin
      and Changsha children, and attained full maturation 1 year earlier, in both girls
      and boys. CONCLUSION: The RUS maturity of the Beijing children was comparable
      with that of Tokyo children, except for the boys between 11 and 13 years.
      Variability of the RUS maturation among the Chinese children was greater than
      that found among the TW3, Tokyo and Beijing children.

PMID- 16099777
TI  - Village distance from urban centre as the prime modernization variable in
      differences in blood pressure and body mass index of adults of the Purari delta
      of the Gulf Province, Papua New Guinea.
AB  - OBJECTIVE: The study examined the extent to which the geographical proximity of
      villages to an urban centre and other modernization variables are associated with
      variation in blood pressure and body mass index (BMI) of adults of the Purari
      delta of the Gulf Province, Papua New Guinea (PNG). METHODS: Mean BMI, systolic
      blood pressure (SBP) and diastolic blood pressure (DBP) of 292 adults surveyed in
      1995-1997 in the Purari delta, PNG, are reported by village of residence, and
      related to modernization variables, including village of residence, urban life,
      urban connectedness, economic status and education. RESULTS: Mean BMI, SBP and
      DBP differ according to village of residence, there being a gradient in mean
      blood pressure from highest in the village closest to the urban centre, Baimuru,
      and lowest in the village most distant from it. The gradients in these variables
      across the three villages are not due to differences in age structures between
      the villages. Place of residence, which represents the distance from town, has
      the greatest impact on the BMI of males, while among the females, the number of
      relatives living in urban centres had a significant effect on BMI. For both males
      and females, place of residence has the strongest effect on SBP. While for the
      males, place of residence is the only significant factor associated with SBP, for
      the females, SBP is also associated with BMI, level of income and to a lesser
      extent with age. Very similar results were obtained for DBP. CONCLUSIONS:
      Distance to urban centre appears to have a strong effect, relative to other
      modernization variables, on BMI and blood pressure, this effect being far
      stronger for males than for females. In large part, this effect operates by way
      of differences in number of sources of income as well as number of close
      relatives of women who are resident in an urban centre. Reasons for the male
      female differences observed may include gender differences in degree of mobility,
      and possibly greater physical sensitivity of males to the environment than
      females. Traditionally, there have been clear divisions of labour between males
      and females, the latter spending longer in subsistence activities than the
      former. It is speculated that males have more free time to travel to town should
      they wish, while women may travel to town to take produce to market, and be
      limited by how much time they spend in town when they are there, by the need to
      return to carry out household and subsistence tasks. It may also be that young
      adult males are more susceptible to modernization, in that they exhibit a greater
      degree of non-conformity than young women, and may be more favourably disposed to
      adopt aspects of western lifestyle.

PMID- 16099778
TI  - Age trends of sibling resemblance for height, weight and BMI during growth in a
      mixed longitudinal sample from Sarsuna-Barisha, India.
AB  - BACKGROUND: Even though some studies have considered that sibling resemblance
      remains constant throughout the life cycle, several investigations emphasize the
      importance of age and its interactions with genetic and environmental factors in
      determining sibling similarity in several bodily traits. In fact, the study of
      age changes in familial resemblance is of great importance for the analysis of
      certain sources of variation observed in growth processes. AIM: The study
      examined sibling resemblance for height, weight and body mass index (BMI) in a
      mixed longitudinal sample from West Bengal, ages 2-19 years, in order to analyse
      the variations with age of the sibling resemblance for these phenotypes during
      growth. SAMPLE AND METHODS: Two hundred and forty-five brothers and 213 sisters
      from 138 middle-class nuclear families living in a semi-urban area of South
      Kolkata, India were analysed. The analysis of sibling resemblance was performed
      through correlations estimated by the maximum-likelihood method. The patterns of
      different trends of sibling resemblance with age were examined by fitting a cubic
      non-linear regression to the observed correlations. RESULTS: The results show
      clear variations with age in the sibling resemblance for the traits height and
      weight, though to a lesser extent for BMI. In general, we found the highest
      correlation values during the period of infancy, a remarkable decrease during
      puberty, and a trend of increase towards the end of the growth cycle. CONCLUSION:
      The study confirms the effect of age on the degree of similarity among siblings
      for height, weight and BMI in the sample. The sharp decline of correlation at
      adolescence can be interpreted in terms of the individual variation in age of
      reaching the adolescent growth spurt.

PMID- 16099779
TI  - APOE polymorphism distribution among Native Americans and related populations.
AB  - BACKGROUND: Apolipoprotein E (apoE, protein; APOE, gene) plays a central role in
      lipid metabolism. Three common alleles, E*2, E*3 and E*4 have quantitative
      effects on lipid and lipoproteins levels, which are major risk determinants of
      cardiovascular diseases in several populations. Given their clinical
      significance, it is of interest to know the distribution of APOE variants in
      populations from diverse ethnic groups, as well as to determine if this
      polymorphism presents variations that might be associated with given evolutionary
      factors. AIM: We report the distribution of APOE polymorphisms in Native American
      populations from South America, comparing it with other native populations of the
      Americas and Siberia. SUBJECTS AND METHODS: The sample consisted of 315
      individuals from nine Native American populations living at subtropical latitudes
      of Argentina, Brazil and Paraguay. The extended analysis included 50 populations
      across South and North America, Greenland and Siberia. The geographic patterns of
      the variation were investigated through correlation analysis, spatial
      autocorrelation and analysis molecular of variance (AMOVA). RESULTS: The
      incidence of the most common allele (APOE*3) in the sample analysed ranged from
      0.78 to 0.98. The second allele in prevalence, APOE*4, varied from 0.00 to 0.17.
      The rare allele APOE*2 was found in five of the nine populations investigated.
      This variant was found in a male with both maternal and paternal Native American
      lineages, suggesting that this allele is present in Native Americans and hence
      should not be used as an indicator of admixture. APOE*3 and APOE*4 present,
      respectively, positive and negative associations with latitude, although the
      pattern is much more pronounced in the Northern Hemisphere than in South America.
      APOE*2 increases its frequency with latitude but this pattern is statistically
      significant only in South America. CONCLUSION: The overall APOE spatial pattern
      seems, in general, compatible with a directional demographic expansion which
      occurred in north-eastern Asia and much of the New World. The APOE*2 allele shows
      this pattern in South America but a random distribution in the Northern
      Hemisphere, suggesting that the possibility of selection should not be discarded.

PMID- 16099780
TI  - Relationships between anthropometry, cardiorespiratory fitness indices and
      physical activity levels in different age and sex groups in rural Senegal (West
      Africa).
AB  - BACKGROUND: A high level of activity is commonplace in traditional subsistence
      societies. Physiological characteristics of individuals, including body
      composition and physical fitness, could be limiting factors when performing daily
      tasks. OBJECTIVES: The study investigated the relationships between
      cardiorespiratory fitness, nutritional status and physical activity patterns, so
      as to test the hypothesis that these relationships are less straightforward in
      children than in adults. STUDY DESIGN: Four different groups of individuals from
      rural Senegal were investigated: 99 10-13-year-old children of both sexes (11.1
      +/- 1.5 years old) from two settings in Senegal (Lambaye and Podor), 43
      adolescent girls (15.5 +/- 0.5 years), and 30 adult women (17-40 years). METHODS:
      Subjects undertook a step test, and anthropometric measurements were collected.
      Continuous heart rate (HR) monitoring was performed for 8-12 h. The flex-HR
      method was used to estimate levels of activity (per cent of time spent under or
      over the flex-HR). RESULTS: Ten to 13-year-old children and adolescent girls
      presented slight degrees of malnutrition. Adult women were apparently not
      nutritionally deprived. Differences in cardiorespiratory fitness were found among
      10-13-year-old children, while adult women performed better than adolescent
      girls. Children from Lambaye had a higher level of activity than children from
      Podor. Similarly, adult women were more active than adolescent girls. No
      relationships were found between cardiorespiratory or anthropometric measurements
      and per cent of time spent above the flex-HR (> flex-HR) in 10-13-year-old
      children. In contrast, in adult women and adolescent girls, body composition and
      cardiorespiratory indices were significant predictors of activity levels.
      CONCLUSION: Our data support the hypothesis that activity levels are less
      dependent upon physiological characteristics in children than in adults in
      traditional subsistence societies.

PMID- 16099781
TI  - Estimating puberty in a prehistoric skeletal collection.
AB  - A method was introduced to estimate the age of puberty in prehistoric skeletal
      collections using stages of fusion of the epiphyses of the distal humerus,
      proximal radius and proximal ulna, as well as fusion of the ilium, ischium and
      pubis. Fusion of these bones is associated with the hormonal release coincident
      with the onset of puberty. Dental age-at-death and stage of fusion of these bones
      were compared in 22 sub-adult individuals from the Moundville (1TU500) site in
      Alabama, USA. The age for the onset of puberty in this skeletal sample from
      Moundville, including both males and females, was estimated to be 14.95 +/- 2.53
      years. These results represent an initial application of this methodology to a
      small data set. The application of this method on a larger scale may provide a
      better understanding of reproductive lifespans in earlier populations, as well as
      insight into possible effects of nutritional or socio-economic differences on the
      sexual development of children within those populations.

PMID- 16099783
TI  - The endogenous cannabinoid, anandamide, induces cell death in colorectal
      carcinoma cells: a possible role for cyclooxygenase 2.
AB  - BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) is upregulated in most colorectal
      cancers and is responsible for metabolism of the endogenous cannabinoid,
      anandamide, into prostaglandin-ethanolamides (PG-EAs). The aims of this study
      were to determine whether anandamide and PG-EAs induce cell death in colorectal
      carcinoma (CRC) cells, and whether high levels of COX-2 in CRC cells could be
      utilised for their specific targeting for cell death by anandamide. METHODS: We
      determined the effect of anandamide on human CRC cell growth by measuring cell
      growth and cell death, whether this was dependent on COX-2 protein expression or
      enzyme activity, and the potential involvement of PG-EAs in induction of cell
      death. RESULTS: Anandamide inhibited the growth of CRC cell lines HT29 and
      HCA7/C29 (moderate and high COX-2 expressors, respectively) but had little effect
      on the very low COX-2 expressing CRC cell line, SW480. Induction of cell death in
      HT29 and HCA7/C29 cell lines was partially rescued by the COX-2 selective
      inhibitor NS398. Cell death induced by anandamide was neither apoptosis nor
      necrosis. Furthermore, inhibition of fatty acid amide hydrolase potentiated the
      non-apoptotic cell death, indicating that anandamide induced cell death was
      mediated via metabolism of anandamide by COX-2, rather than its degradation into
      arachidonic acid and ethanolamine. Interestingly, both PGE2-EA and PGD2-EA
      induced classical apoptosis. CONCLUSIONS: These findings suggest anandamide may
      be a useful chemopreventive/therapeutic agent for colorectal cancer as it targets
      cells that are high expressors of COX-2, and may also be used in the eradication
      of tumour cells that have become resistant to apoptosis.

PMID- 16099784
TI  - A randomised controlled trial of self-help interventions in patients with a
      primary care diagnosis of irritable bowel syndrome.
AB  - INTRODUCTION: Functional abdominal symptoms are very common and account for
      nearly two million primary care consultations in Britain every year and produce
      significant morbidity. The aims of this study were to evaluate the impact of two
      self-help interventions on consultation rates and symptom severity in patients
      with a primary care diagnosis of irritable bowel syndrome. METHODS: A total of
      420 patients from 54 primary care centres were randomised either to receive self
      help information in the form of a guidebook or the guidebook plus a "self-help"
      group meeting or to be in a control group receiving neither intervention. Data
      were collected using questionnaires and primary care records. RESULTS: At one
      year, patients in the guidebook group had a 60% reduction in primary care
      consultations (p < 0.001) and a reduction in perceived symptom severity (p <
      0.001) compared with controls. Allocation to the self-help group conferred no
      additional benefit. Actual symptom scores did not change significantly in any
      group. Costs per patient were reduced by Pounds 73 (confidence interval Pounds
      43, Pounds 103) or 40% per year. CONCLUSION: Introduction of a self-help
      guidebook results in a reduction in primary care consultations, a perceived
      reduction in symptoms, and significant health service savings. This suggests that
      patients attending their primary care physician with functional abdominal
      symptoms should be offered self-help information as part of their management.

PMID- 16099785
TI  - Colorectal cancer prognosis: is it all mutation, mutation, mutation?
AB  - For the 500,000 new cases of colorectal cancer in the world each year,
      identification of patients with a worse prognosis and those who are more likely
      to respond to treatment is a challenge. There is an increasing body of evidence
      correlating genetic mutations with outcome in tumours derived from human
      colorectal cancer cohorts. K-ras, but not p53 or APC, mutations appear to be
      associated with poorer overall survival in colorectal cancer patients.

PMID- 16099786
TI  - ASCA: genetic marker, predictor of disease, or marker of a response to an
      environmental antigen?

PMID- 16099787
TI  - Osteopontin: a new addition to the constellation of cytokines which drive T
      helper cell type 1 responses in Crohn's disease.

PMID- 16099788
TI  - Silencing RNA: a novel treatment for pancreatic cancer?

PMID- 16099789
TI  - T cells in peripheral blood after gluten challenge in coeliac disease.
AB  - BACKGROUND: Current understanding of T cell epitopes in coeliac disease (CD)
      largely derives from intestinal T cell clones in vitro. T cell clones allow
      identification of gluten peptides that stimulate T cells but do not quantify
      their contribution to the overall gluten specific T cell response in individuals
      with CD when exposed to gluten in vivo. AIMS: To determine the contribution of a
      putative dominant T cell epitope to the overall gliadin T cell response in HLA
      DQ2 CD in vivo. PATIENTS: HLA-DQ2+ individuals with CD and healthy controls.
      METHODS: Subjects consumed 20 g of gluten daily for three days. Interferon gamma
      (IFN-gamma) ELISPOT was performed using peripheral blood mononuclear cells (PBMC)
      to enumerate and characterise peptide and gliadin specific T cells before and
      after gluten challenge. RESULTS: In 50/59 CD subjects, irrespective of homo- or
      heterozygosity for HLA-DQ2, IFN-gamma ELISPOT responses for an optimal
      concentration of A-gliadin 57-73 Q-E65 were between 10 and 1500 per million PBMC,
      equivalent to a median 51% of the response for a "near optimal" concentration of
      deamidated gliadin. Whole deamidated gliadin and gliadin epitope specific T cells
      induced in peripheral blood expressed an intestinal homing integrin (alpha4beta7)
      and were HLA-DQ2 restricted. Peripheral blood T cells specific for A-gliadin 57
      73 Q-E65 are rare in untreated CD but can be predictably induced two weeks after
      gluten exclusion. CONCLUSION: In vivo gluten challenge is a simple safe method
      that allows relevant T cells to be analysed and quantified in peripheral blood by
      ELISPOT, and should permit comprehensive high throughput mapping of gluten T cell
      epitopes in large numbers of individuals with CD.

PMID- 16099790
TI  - Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide
      2 analogue, improves intestinal function in short bowel syndrome patients.
AB  - BACKGROUND AND AIMS: Glucagon-like peptide 2 (GLP-2) may improve intestinal
      absorption in short bowel syndrome (SBS) patients with an end jejunostomy.
      Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant GLP-2 analogue,
      prolongs the intestinotrophic properties of GLP-2 in animal models. The safety
      and effect of teduglutide were investigated in SBS patients with and without a
      colon in continuity. METHODS: Teduglutide was given subcutaneously for 21 days
      once or twice daily to 16 SBS patients in the per protocol investigational group,
      10 with end jejunostomy (doses of 0.03 (n = 2), 0.10 (n = 5), or 0.15 (n = 3)
      mg/kg/day), one with <50% colon in continuity (dose 0.03 mg/kg/day), and five
      with > or = 50% colon in continuity (dose 0.10 mg/kg/day). Nutrient balance
      studies, D-xylose tests, and intestinal mucosa biopsies were performed at
      baseline, on the last three days of treatment, and after three weeks of follow
      up. Pre-study fasting native GLP-2 levels were determined for the five patients
      with > or = 50% colon in continuity. RESULTS: Pooled across groups and compared
      with baseline, teduglutide increased absolute (+743 (477) g/day; p<0.001) and
      relative (+22 (16)%; p<0.001) wet weight absorption, urine weight (+555 (485)
      g/day; p<0.001), and urine sodium excretion (+53 (40) mmol/day; p<0.001).
      Teduglutide decreased faecal wet weight (-711 (734) g/day; p = 0.001) and faecal
      energy excretion (-808 (1453) kJ/day (-193 (347) kcal/day); p = 0.040). In SBS
      patients with end jejunostomy, teduglutide significantly increased villus height
      (+38 (45)%; p = 0.030), crypt depth (+22 (18)%; p = 0.010), and mitotic index
      (+115 (108)%; p = 0.010). Crypt depth and mitotic index did not change in colonic
      biopsies from SBS patients with colon in continuity. The most common side effects
      were enlargement of the stoma nipple and mild lower leg oedema. The improvements
      in intestinal absorption and decreases in faecal excretion noted after treatment
      had reversed after the drug free follow up period. A controlled study with a more
      robust design is ongoing in order to determine the optimal dosage of teduglutide
      for SBS patients to achieve the maximal effect and utility of this drug in
      clinical practice. CONCLUSION: Teduglutide, at three dose levels for 21 days, was
      safe and well tolerated, intestinotrophic, and significantly increased intestinal
      wet weight absorption in SBS patients with an end jejunostomy or a colon in
      continuity.

PMID- 16099791
TI  - Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as
      predictors of inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Several antibodies have been reported in the sera of
      patients with Crohn's disease (CD) and ulcerative colitis (UC). The most commonly
      described are anti-Saccharomyces cerevisiae mannan antibodies (ASCA) in CD and
      perinuclear antineutrophil cytoplasm antibodies (pANCA) in UC. Familial
      clustering of these antibodies has been described, suggesting they might be
      genetic markers. Our aim was to investigate the presence of these antibodies
      before the emergence of overt clinical manifestations. METHODS: Since 1980, the
      Israeli Defense Force (IDF) Medical Corps Serum Repository has stored serum
      samples obtained systematically from 5% of all recruits on enlistment, and from
      the same population on discharge from compulsory military service. We evaluated
      serum samples obtained from 32 subjects with CD and eight with UC before they
      were clinically diagnosed, along with samples from matched controls. RESULTS:
      ASCA were present in 10/32 (31.3%) CD patients before clinical diagnosis compared
      with 0/95 (0%) controls (p<0.001). None of the eight patients with serum samples
      available before diagnosis of UC were ASCA positive. ASCA was positive in 54.5%
      of patients after diagnosis of CD. The mean interval between ASCA detection and
      diagnosis was 38 months. In 90% of patients, antibodies were detected in the
      first available serum sample; therefore, measurements of the average time from
      the presence of ASCA to diagnosis may be even longer. pANCA were present in 2/8
      (25%) patients with available sera before the diagnosis of UC. None of their 24
      matched controls were positive (p = 0.014). CONCLUSIONS: ASCA and pANCA may
      predict development of inflammatory bowel disease years before the disease is
      clinically diagnosed.

PMID- 16099792
TI  - Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune
      response.
AB  - BACKGROUND AND AIMS: The pathogenesis of Crohn's disease (CD), a chronic
      inflammatory bowel disease characterised by a Th1 immune response, remains
      unclear. Osteopontin (OPN) is a phosphoprotein known as an adhesive bone matrix
      protein. Recent studies have shown that OPN plays an important role in lymphocyte
      migration, granuloma formation, and interleukin 12 (IL-12) production. The
      present study investigated expression and the pathophysiological role of OPN in
      CD. METHODS: Plasma OPN concentration was measured by enzyme linked immunosorbent
      assay. Expression of OPN in human intestinal mucosa was determined using reverse
      transcription-polymerase chain reaction and western blot, and localisation of OPN
      was examined by immunohistochemistry. Expression of integrin beta3, an OPN
      receptor, on lamina propria mononuclear cells (LPMC) was assessed by flow
      cytometry. Functional activation of OPN in LPMC was investigated by measuring the
      production of cytokines. RESULTS: Plasma OPN concentration was significantly
      higher in patients with CD compared with normal controls or patients with
      ulcerative colitis (UC). OPN was upregulated in intestinal mucosa from UC and CD
      patients. OPN producing cells were epithelial or IgG producing plasma cells, or
      partial macrophages. OPN was detected in areas surrounding granuloma from mucosa
      in CD. Integrin beta3 expressing macrophages infiltrated inflamed mucosa in UC
      and CD; in contrast, there was no expression of integrin beta3 on intestinal
      macrophages in normal mucosa. OPN induced production of IL-12 from LPMC in CD but
      not in normal controls or UC. CONCLUSIONS: Increased OPN expression facilitates
      cytokine production and is closely involved in the Th1 immune response associated
      with CD.

PMID- 16099793
TI  - An exceptional cause for recurrent vomiting.

PMID- 16099794
TI  - An unusual case of hepatosplenomegaly.

PMID- 16099795
TI  - A challenging presentation of left upper quadrant pain.

PMID- 16099796
TI  - A case of progressive dysphagia.

PMID- 16099797
TI  - Detection and identification of bacterial DNA in serum from patients with acute
      pancreatitis.
AB  - BACKGROUND AND AIMS: Bacterial infections are common complications in patients
      with acute pancreatitis, and translocation of bacteria from the intestinal lumen
      is probably the first step in the pathogenesis of these infections. As blood
      cultures in afebrile patients are usually negative, more sensitive methods to
      investigate this hypothesis in patients are needed. Our group has recently
      developed a method to detect the presence of bacterial DNA in biological fluids,
      and we aimed to detect bacterial DNA in patients with acute pancreatitis, as
      molecular evidences of bacterial translocation. METHODS: Samples of blood were
      obtained on three consecutive days within the first six days after admission.
      Bacterial DNA was detected using a polymerase chain reaction based method, and an
      automated DNA nucleotide sequencing process allowed identification of bacteria
      species. RESULTS: Thirty one consecutively admitted patients with acute
      pancreatitis were studied. Bacterial DNA was detected in six patients (19.3%),
      and the sequencing process allowed identification of Citrobacter freundii and
      Pseudomonas aeruginosa. In two patients the same bacteria detected at admission
      was detected 24 hours later (above 99.9% homology of nucleotide sequence). Basic
      clinical and biochemical characteristics were similar among patients with or
      without the presence of bacterial DNA. CONCLUSION: Detection of gram negative
      bacteria derived bacterial DNA in our series supports the contention that
      bacterial translocation is a systemic process in approximately 20% of patients
      with acute pancreatitis that does not seem to be related to the severity of the
      episode or immediate development of infection.

PMID- 16099798
TI  - Variants of bcl-2 specific siRNA for silencing antiapoptotic bcl-2 in pancreatic
      cancer.
AB  - BACKGROUND AND AIMS: Pancreatic cancer remains a devastating diagnosis with only
      limited therapeutic options. Specific inhibition of expression of target genes
      has become possible using small interfering (si) RNAs. We therefore investigated
      how far siRNA specific for bcl-2 may serve as a therapeutic option for pancreatic
      cancer in vitro and in vivo. METHODS: siRNAs targeting two different regions in
      the bcl-2 gene were transfected to YAP C and DAN G pancreatic carcinoma cells and
      human foreskin fibroblasts. Permutations were generated by changing 3' and 5'
      overhangs and varying the length of the paired RNA duplex. Transfection efficacy
      was determined using FITC labelled siRNAs and fluorescence microscopy. Cell
      survival and apoptosis were quantified at 24-120 hours. Pancreatic cancer
      xenografts in male nude mice were treated intraperitoneally with siRNAs daily for
      24 days. siRNA pharmacokinetics in vivo were assessed using radioactively
      labelled siRNAs. Total protein and RNA were extracted for western Blot analysis
      and quantitative polymerase chain reaction. RESULTS AND CONCLUSIONS: Bcl-2
      specific siRNAs specifically inhibited expression of the target gene in vitro and
      in vivo. Antiproliferative and proapoptotic effects were observed in tumour cells
      but not in fibroblasts or non-malignant tissues. siRNA permutations and diverse
      overhangs influenced gene silencing efficacy. siRNA was quickly distributed to
      all organs and excreted via the kidney and liver. Bcl-2 specific siRNA is a
      promising adjunctive treatment for pancreatic carcinoma.

PMID- 16099799
TI  - Infection, inflammation, and gastrointestinal cancer.

PMID- 16099800
TI  - Use of psychopharmacological agents for functional gastrointestinal disorders.

PMID- 16099801
TI  - Cap polyposis: an inflammatory disorder or a spectrum of mucosal prolapse
      syndrome?

PMID- 16099802
TI  - Novel presentation of coeliac disease after following the Atkins' low
      carbohydrate diet.

PMID- 16099803
TI  - Chronic intestinal pseudo-obstruction due to lymphocytic leiomyositis: is there a
      place for immunomodulatory therapy?

PMID- 16099804
TI  - UK guidelines for management of acute pancreatitis: is it time to change?

PMID- 16099805
TI  - RANK ligand and osteoprotegerin: emerging roles in mucosal inflammation.

PMID- 16099806
TI  - Inflammatory biomarkers predict relapse in IBD.

PMID- 16099807
TI  - Deranged smooth muscle alpha-actin expression as a biomarker of intestinal pseudo
      obstruction.

PMID- 16099808
TI  - Synbiotic therapy for ulcerative colitis.

PMID- 16099809
TI  - Colitis evolving into ulcerative colitis.

PMID- 16099810
TI  - Response to steroid therapy of sclerosing cholangitis after duodenopancreatectomy
      due to autoimmune pancreatitis.

PMID- 16099811
TI  - Is there an ideal prognostic model for hepatocellular carcinoma?

PMID- 16099812
TI  - Calprotectin and IBD.

PMID- 16099813
TI  - Genetic analysis of early endocrine pancreas formation in zebrafish.
AB  - Endocrine pancreas of zebrafish consist of at least four different cell types
      that function similarly to mammalian pancreatic islet. No mutants specifically
      affecting formation of the endocrine pancreas have been identified during the
      previous large-scale mutagenesis screens in zebrafish due to invisibility of a
      pancreatic islet. We combined in situ hybridization method to visualize
      pancreatic islet with an ethyl-nitroso-urea mutagenesis screen to identify novel
      genes involved in pancreatic islet formation in zebrafish. We screened 900
      genomes and identified 11 mutations belonging to nine different complementation
      groups. These mutants fall into three major phenotypic classes displaying
      severely reduced insulin expression, reduced insulin expression with abnormal
      islet morphology, or abnormal islet morphology with relatively normal number of
      insulin expressing cells. Seven of these mutants do not have any other visible
      phenotypes associated. These mutations affect different processes in pancreatic
      islet development. Additional analysis on glucagon and somatostatin cell
      specification revealed that somatostatin cells are specified at a separate domain
      from insulin cells whereas glucagon cells are specified adjacent to insulin
      cells. Furthermore, glucagon cells and somatostatin cells are always associated
      with insulin cells in mutants that have scattered insulin expression. These data
      indicate that there are separate mechanisms regulating endocrine cell migration,
      proliferation, and differentiation. Further study on these mutants will reveal
      important information on novel genes involved in pancreatic islet cell
      specification and morphogenesis.

PMID- 16099814
TI  - Impaired reproductive behavior by lack of GluR-B containing AMPA receptors but
      not of NMDA receptors in hypothalamic and septal neurons.
AB  - The roles of ionotropic glutamate receptors in mammalian reproduction are
      unknown. We therefore generated mice lacking a major subtype of (S)-alpha-amino-3
      hydroxy-5-methyl-isoxazolepropionic acid (AMPA) receptors or all N-methyl-d
      aspartate (NMDA) receptors in GnRH neurons and other mainly limbic system
      neurons, primarily in hypothalamic and septal areas. Male mice without NMDA
      receptors in these neurons were not impaired in breeding and exhibited similar
      GnRH secretion as control littermates. However, male mice lacking GluR-B
      containing AMPA receptors in these neurons were poor breeders and severely
      impaired in reproductive behaviors such as aggression and mounting. Testis and
      sperm morphology, testis weight, and serum testosterone levels, as well as GnRH
      secretion, were unchanged. Contact with female cage bedding failed to elicit male
      sexual behavior in these mice, unlike in control male littermates. Their female
      counterparts had unchanged ovarian morphology, had bred successfully, and had
      normal litter sizes but exhibited pronounced impairments in maternal behaviors
      such as pup retrieval and maternal aggression. Our results suggest that NMDA
      receptors and GluR-B containing AMPA receptors are not essential for fertility,
      but that GluR-B containing AMPA receptors are essential for male and female
      reproduction-related behaviors, perhaps by mediating responses to pheromones or
      odorants.

PMID- 16099815
TI  - Megalin is a receptor for apolipoprotein M, and kidney-specific megalin
      deficiency confers urinary excretion of apolipoprotein M.
AB  - Apolipoprotein (apo) M is a novel apolipoprotein belonging to the lipocalin
      protein superfamily, i.e. proteins binding small lipophilic compounds. Like other
      apolipoproteins, it is expressed in hepatocytes and secreted into plasma where it
      associates with high-density lipoprotein particles. In addition, apoM is
      expressed at high levels in the kidney tubule cells. In this study, we show that
      the multiligand receptor megalin, which is expressed in kidney proximal tubule
      cells, is a receptor for apoM and mediates its uptake in the kidney. To examine
      apoM binding to megalin, a recombinant apoM was expressed in Escherichia coli and
      used in surface plasmon resonance and cell culture studies. The results showed
      apoM binding to immobilized megalin [dissociation constant (Kd) approximately 0.3
      1 microm] and that the apoM was endocytosed by cultured rat yolk sac cells in a
      megalin-dependent manner. To examine the importance of apoM binding by megalin in
      vivo, we analyzed mice with a tissue-specific deficiency of megalin in the
      kidney. Megalin deficiency was associated with pronounced urinary excretion of
      apoM, whereas apoM was not detected in normal mouse, human, or rat urine. Gel
      filtration analysis showed that the urinary apoM-containing particles were small
      and devoid of apoA-I. The results suggest that apoM binds to megalin and that
      megalin-mediated endocytosis in kidney proximal tubules prevents apoM excretion
      in the urine.

PMID- 16099816
TI  - Serum- and glucocorticoid-regulated kinase 1 regulates ubiquitin ligase neural
      precursor cell-expressed, developmentally down-regulated protein 4-2 by inducing
      interaction with 14-3-3.
AB  - Serum- and glucocorticoid-regulated kinase 1 (SGK1) is an aldosterone-regulated
      early response gene product that regulates the activity of several ion transport
      proteins, most notably that of the epithelial sodium channel (ENaC). Recent
      evidence has established that SGK1 phosphorylates and inhibits Nedd4-2 (neural
      precursor cell-expressed, developmentally down-regulated protein 4-2), a
      ubiquitin ligase that decreases cell surface expression of the channel and
      possibly stimulates its degradation. The mechanistic basis for this SGK1-induced
      Nedd4-2 inhibition is currently unknown. In this study we show that SGK1-mediated
      phosphorylation of Nedd4-2 induces its interaction with members of the 14-3-3
      family of regulatory proteins. Through functional characterization of Nedd4-2
      mutant proteins, we demonstrate that this interaction is required for SGK1
      mediated inhibition of Nedd4-2. The concerted action of SGK1 and 14-3-3 appears
      to disrupt Nedd4-2-mediated ubiquitination of ENaC, thus providing a mechanism by
      which SGK1 modulates the ENaC-mediated Na(+) current. Finally, the expression
      pattern of 14-3-3 is also consistent with a functional role in distal nephron
      Na(+) transport. These results demonstrate a novel, physiologically significant
      role for 14-3-3 proteins in modulating ubiquitin ligase-dependent pathways in the
      control of epithelial ion transport.

PMID- 16099817
TI  - A docking site for G protein betagamma subunits on the parathyroid hormone 1
      receptor supports signaling through multiple pathways.
AB  - The G protein-coupled receptor for PTH and PTH-related protein (PTH1R) signals
      via many intracellular pathways. The purpose of this work is to investigate a G
      protein binding site on an intracellular domain of the PTH1R. The carboxy
      terminal, cytoplasmic tail of the PTH1R fused to glutathione-S-transferase
      interacts with Gi/o proteins in vitro. All three subunits of the heterotrimer
      interact with the receptor C-tail. Activation of the heterotrimeric complex with
      GTPgammaS has no effect on Gbetagamma interactions, but markedly disrupts binding
      of the Galphai/o subunits to the receptor tail, suggesting that direct Gbetagamma
      binding indirectly links Galpha subunits to this region of the receptor.
      Gbetagamma subunits alone bind the C-tail with an affinity that is comparable to
      the heterotrimeric G protein complex. G protein complexes consisting of
      Galphashis6-beta1gamma2 and Galphaqhis6-beta1gamma2 also interact with the PTH1R
      tail in vitro. The Gbetagamma interaction domain is located on the juxta-membrane
      region of the tail between amino acids 468 and 491. Mutations that disrupt
      Gbetagamma interactions block PTH signaling via phospholipase Cbeta/[Ca2+]i and
      MAPK and markedly reduce signaling via adenylyl cyclase/cAMP. Herein, we define a
      domain on the PTH1R that is capable of binding G protein heterotrimeric complexes
      via direct Gbetagamma interactions.

PMID- 16099818
TI  - Syntaxin 4 facilitates biphasic glucose-stimulated insulin secretion from
      pancreatic beta-cells.
AB  - Numerous overexpression studies have recently implicated Syntaxin 4 as an
      effector of insulin secretion, although its requirement in insulin granule
      exocytosis is unknown. To address this, islets from Syntaxin 4 heterozygous (-/+)
      knockout mice were isolated and compared with islets from wild-type mice. Under
      static incubation conditions, Syntaxin 4 (-/+) islets showed a 60% reduction in
      glucose-stimulated insulin secretion compared with wild-type islets. Perifusion
      analyses revealed that Syntaxin 4 (-/+) islets secreted 50% less insulin during
      the first phase of glucose-stimulated insulin secretion and that this defect
      could be fully restored by the specific replenishment of recombinant Syntaxin 4.
      This essential role for Syntaxin 4 in secretion from the islet was localized to
      the beta-cells because small interfering RNA-mediated depletion of Syntaxin 4 in
      MIN6 beta-cells abolished glucose-stimulated insulin secretion. Moreover,
      immunofluorescent confocal microscopy revealed that Syntaxin 4 was principally
      localized to the beta-cells and not the alpha-cells of the mouse islet.
      Remarkably, islets isolated from transgenic mice that express 2.4-fold higher
      levels of Syntaxin 4 relative to wild-type mice secreted approximately 35% more
      insulin during both phases of insulin secretion, suggesting that increased
      Syntaxin 4 may be beneficial for enhancing biphasic insulin secretion in a
      regulated manner. Taken together, these data support the notion that Syntaxin 4
      based SNARE complexes are essential for biphasic insulin granule fusion in
      pancreatic beta-cells.

PMID- 16099819
TI  - Overexpression of the coactivator bridge-1 results in insulin deficiency and
      diabetes.
AB  - Multiple forms of heritable diabetes are associated with mutations in
      transcription factors that regulate insulin gene transcription and the
      development and maintenance of pancreatic beta-cell mass. The coactivator Bridge
      1 (PSMD9) regulates the transcriptional activation of glucose-responsive
      enhancers in the insulin gene in a dose-dependent manner via PDZ domain-mediated
      interactions with E2A transcription factors. Here we report that the pancreatic
      overexpression of Bridge-1 in transgenic mice reduces insulin gene expression and
      results in insulin deficiency and severe diabetes. Dysregulation of Bridge-1
      signaling increases pancreatic apoptosis with a reduction in the number of
      insulin-expressing pancreatic beta-cells and an expansion of the complement of
      glucagon-expressing pancreatic alpha-cells in pancreatic islets. Increased
      expression of Bridge-1 alters pancreatic islet, acinar, and ductal architecture
      and disrupts the boundaries between endocrine and exocrine cellular compartments
      in young adult but not neonatal mice, suggesting that signals transduced through
      this coactivator may influence postnatal pancreatic islet morphogenesis. Signals
      mediated through the coactivator Bridge-1 may regulate both glucose homeostasis
      and pancreatic beta-cell survival. We propose that coactivator dysfunction in
      pancreatic beta-cells can limit insulin production and contribute to the
      pathogenesis of diabetes.

PMID- 16099820
TI  - Posttranscriptional mechanisms contribute to osmotic regulation of ANG type 1
      receptors in cultured rat renomedullary interstitial cells.
AB  - Previously, we showed that ANG II receptors in cultured rat renomedullary
      interstitial cells (RMICs) are osmotically regulated (19). The current study
      examined the mechanisms underlying this osmotic regulation in RMICs cultured in
      isoosmotic (300 mosmol/kgH2O) and hyperosmotic (600 mosmol/kgH2O) conditions.
      Radioligand competition analysis coupled with RNase protection assays (RPA) and
      ligand-mediated receptor internalization studies revealed that RMICs primarily
      express the type 1a angiotensin receptor (AT(1a)R). When cultured under
      hyperosmotic conditions, the density (B(max)) of AT1R in RMIC membranes decreased
      by 31% [B(max) (pmol/mg protein): 300 mosmol/kgH2O, 6.44 +/- 0.46 vs. 600
      mosmol/kgH2O, 4.42 +/- 0.37, n = 8, P < 0.01], under conditions in which no
      detectable changes in AT(1a)R mRNA expression or in the kinetics of ligand
      mediated AT1R internalization were observed. RNA electromobility shift assays
      showed that RNA protein complex (RPC) formation between RMIC cytosolic RNA
      binding proteins and the 5' leader sequence (5'LS) of the AT(1a)R was increased
      1.5-fold under hyperosmotic conditions [5'LS RPC (arbitrary units): 300
      mosmol/kgH2O, 0.79 +/- 0.08 vs. 600 mosmol/kgH2O, 1.17 +/- 0.07, n = 4, P <
      0.01]. These results suggest that the downregulation of AT(1a)R expression in
      RMICs cultured under hyperosmotic conditions is regulated at the
      posttranscriptional level by RNA binding proteins that interact within the 5'LS
      of the AT(1a)R mRNA. The downregulation of AT(1a)R expression under hyperosmotic
      conditions may be an important mechanism by which the activity of ANG II is
      regulated in the hyperosmotic renal medulla.

PMID- 16099821
TI  - Differential effects of superoxide on luminal and basolateral Na+/H+ exchange in
      the thick ascending limb.
AB  - Superoxide (O2-) increases Na+ reabsorption in the thick ascending limb (THAL) by
      enhancing Na/K/2Cl cotransport. However, the effects of O2- on other THAL
      transporters, such as Na(+)/H+ exchangers, are unknown. We hypothesized that O2-
      stimulates Na(+)/H+ exchange in the THAL. We assessed total Na(+)/H+ exchange
      activity by measuring recovery of intracellular pH (pH(i)) after acid loading in
      isolated perfused THALs before and after adding xanthine oxidase (XO) and
      hypoxanthine (HX). We found that XO and HX decreased total pH(i) recovery rate
      from 0.26 +/- 0.05 to 0.21 +/- 0.04 pH units/min (P < 0.05), and this net
      inhibition decreased steady-state pH(i) from 7.52 to 7.37. Because THALs have
      different Na(+)/H+ exchanger isoforms on the luminal and basolateral membrane, we
      tested the effects of xanthine oxidase and hypoxanthine on luminal and
      basolateral Na(+)/H+ exchange by adding dimethylamiloride to either the bath or
      lumen. Xanthine oxidase and hypoxanthine increased luminal Na(+)/H+ exchange from
      3.5 +/- 0.8 to 6.7 +/- 1.4 pmol.min(-1).mm(-1) (P < 0.01) but decreased
      basolateral Na(+)/H+ exchange from 10.8 +/- 1.8 to 6.8 +/- 1.1 pmol.min(-1).mm(
      1) (P < 0.007). To ascertain whether these effects were caused by O2- or H2O2, we
      examined the ability of tempol, a superoxide dismutase mimetic, to block these
      effects. In the presence of tempol, xanthine oxidase and hypoxanthine had no
      effect on luminal or basolateral Na(+)/H+ exchange. We conclude that O2- inhibits
      basolateral and stimulates luminal Na(+)/H+ exchangers, perhaps because different
      isoforms are expressed on each membrane. Inhibition of basolateral Na(+)/H+
      exchange may enhance stimulation of luminal Na(+)/H+ exchange by providing
      additional protons to be extruded across the luminal membrane. Together, the
      effects of O2- on Na(+)/H+ exchange may increase net HCO3- reabsorption by the
      THAL.

PMID- 16099822
TI  - Medullary lateral tegmental field mediates the cardiovascular but not respiratory
      component of the Bezold-Jarisch reflex in the cat.
AB  - We determined the effects of bilateral microinjection of muscimol and excitatory
      amino acid receptor antagonists into the medullary lateral tegmental field (LTF)
      on changes in sympathetic nerve discharge (SND), mean arterial pressure (MAP),
      and phrenic nerve activity (PNA; artificially ventilated cats) or intratracheal
      pressure (spontaneously breathing cats) elicited by right atrial administration
      of phenylbiguanide (PBG; i.e., the Bezold-Jarisch reflex) in dial-urethane
      anesthetized cats. The PBG-induced depressor response (-66 +/- 8 mmHg; mean +/-
      SE) was converted to a pressor response after muscimol microinjection in two of
      three spontaneously breathing cats and was markedly reduced in the other cat;
      however, the duration of apnea (20 +/- 3 vs. 17 +/- 7 s) was essentially
      unchanged. In seven paralyzed, artificially ventilated cats, muscimol
      microinjection significantly (P < 0.05) attenuated the PBG-induced fall in MAP (
      39 +/- 7 vs. -4 +/- 4 mmHg) and the magnitude (-98 +/- 1 vs. -35 +/- 13%) and
      duration (15 +/- 2 vs. 3 +/- 2 s) of the sympathoinhibitory response. In
      contrast, the PBG-induced inhibition of PNA was unaffected (3 cats). Similar
      results were obtained by microinjection of an N-methyl-D-aspartate (NMDA)
      receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, into the LTF. In
      contrast, neither the cardiovascular nor respiratory responses to PBG were
      altered by blockade of non-NMDA receptors with 1,2,3,4-tetrahydro-6-nitro-2,3
      dioxobenzo[f]quinoxaline-7-sulfonamide. We conclude that the LTF subserves a
      critical role in mediating the sympathetic and cardiovascular components of the
      Bezold-Jarisch reflex. Moreover, these data show separation of the pathways
      mediating the respiratory and cardiovascular responses of this reflex at a level
      central to bulbospinal outflows to phrenic motoneurons and preganglionic
      sympathetic neurons.

PMID- 16099823
TI  - Spinal cord injury-induced changes in breathing are not due to supraspinal
      plasticity in turtles (Pseudemys scripta).
AB  - After occurrence of spinal cord injury, it is not known whether the respiratory
      rhythm generator undergoes plasticity to compensate for respiratory
      insufficiency. To test this hypothesis, respiratory variables were measured in
      adult semiaquatic turtles using a pneumotachograph attached to a breathing
      chamber on a water-filled tank. Turtles breathed room air (2 h) before being
      challenged with two consecutive 2-h bouts of hypercapnia (2 and 6% CO2 or 4 and
      8% CO2). Turtles were spinalized at dorsal segments D8-D10 so that only pectoral
      girdle movement was used for breathing. Measurements were repeated at 4 and 8 wk
      postinjury. For turtles breathing room air, breathing frequency, tidal volume,
      and ventilation were not altered by spinalization; single-breath (singlet)
      frequency increased sevenfold. Spinalized turtles breathing 6-8% CO2 had lower
      ventilation due to decreased frequency and tidal volume, episodic breathing
      (breaths/episode) was reduced, and singlet breathing was increased sevenfold.
      Respiratory variables in sham-operated turtles were unaltered by surgery.
      Isolated brain stems from control, spinalized, and sham turtles produced similar
      respiratory motor output and responded the same to increased bath pH. Thus
      spinalized turtles compensated for pelvic girdle loss while breathing room air
      but were unable to compensate during hypercapnic challenges. Because isolated
      brain stems from control and spinalized turtles had similar respiratory motor
      output and chemosensitivity, breathing changes in spinalized turtles in vivo were
      probably not due to plasticity within the respiratory rhythm generator. Instead,
      caudal spinal cord damage probably disrupts spinobulbar pathways that are
      necessary for normal breathing.

PMID- 16099824
TI  - Independent ingestion and microstructure of feeding patterns in infant rats
      lacking CCK-1 receptors.
AB  - Otsuka Long-Evans Tokushima fatty (OLETF) rats are a strain of Long-Evans
      Tokushima Otsuka (LETO) rats that do not express CCK-1 receptors, developing in
      adulthood, hyperphagia, obesity, and non-insulin-dependent diabetes mellitus
      (NIDDM). We examined weight gain and meal patterns during a 30-min independent
      ingestion test on postnatal days 2-4 and again on days 9-11 in OLETF and LETO rat
      pups. OLETF pups were significantly heavier compared with their LETO controls at
      both ages, and they consumed significantly more of the sweet milk diet. The
      difference in intake can be attributed to a significant increase in meal size and
      duration. Number of clusters and bursts of licking within a meal were greater in
      OLETF rat pups, with no difference between strains in burst and cluster size.
      Interlick interval (ILI) was not significantly different between OLETF and LETO
      pups. This measure decreased on days 9-11 compared with days 2-4 in both strains.
      Latency to start feeding was significantly shorter on days 2-4 in OLETF vs. LETO
      pups, but this difference disappeared at the second test at the older age. Two-
      to four-day-old OLETF pups consumed a larger volume of milk during the first
      minute of feeding, and their initial lick rate and decay of lick rate were
      significantly larger compared with their LETO controls. Lack of CCK-1 receptors,
      or other OLETF-related abnormalities, therefore, resulted in a satiation deficit,
      leading to increased meal size, hyperphagia, and increased weight gain as early
      as 2-4 postnatal days.

PMID- 16099825
TI  - Long-term hypoxia represses the expression of key genes regulating cortisol
      biosynthesis in the near-term ovine fetus.
AB  - Basal plasma ACTH(1-39) concentrations are elevated in long-term hypoxic (LTH)
      fetal sheep. This study was designed to determine whether the expression of genes
      regulating cortisol biosynthesis was altered after LTH. Pregnant ewes were
      maintained at high altitude (3,820 m) from day 30 of gestation to near term, when
      the animals were transported to the laboratory. Reduced PO2 was maintained by
      nitrogen infusion through a maternal tracheal catheter. On days 137-141, fetal
      adrenal glands were collected from LTH and normoxic control fetuses. Real-time
      PCR was used to quantify mRNA for steroidogenic acute regulatory protein, 17alpha
      hydroxylase (CYP17), 21-hydroxylase (CYP21), cholesterol side-chain cleavage
      (CYP11A1), 3beta-hydroxysteroid dehydrogenase type II (HSD3B2), and the ACTH
      receptor. We analyzed mRNA by slot-blot hybridization and also quantified mRNA
      for transcription factors necessary for adrenocortical development by
      quantitative real-time PCR: steroidogenic factor 1 and dosage-sensitive sex
      reversal, adrenal hypoplasia congenital, critical region on the X chromosome (DAX
      1). Protein was quantified by Western blot analysis. Adrenal mRNAs for CYP17,
      CYP11A1, and the ACTH receptor were significantly reduced in LTH fetal sheep
      compared with levels shown in controls. Similarly, CYP11A1 protein and CYP17
      protein were reduced in the LTH group. CYP21, steroidogenic acute regulatory
      protein, HSD3B2, steroidogenic factor 1, and DAX-1 expressions were not altered
      in response to LTH. We conclude that expression of two key steroidogenic enzymes
      (CYP17, CYP11A1) regulating cortisol biosynthesis and the ACTH receptor is lower
      in response to LTH. This likely represents an adaptive response to LTH, to
      prevent excessive cortisol production that would restrict fetal growth and
      potentially induce preterm delivery.

PMID- 16099826
TI  - Enhanced skeletal muscle arteriolar reactivity to ANG II after recovery from
      ischemic acute renal failure.
AB  - In addition to the long-term renal complications, previous studies suggested that
      after acute renal failure (ARF), rats manifest an increased pressor response to
      an overnight infusion of ANG II. The present study tested whether recovery from
      ARF results in alterations in sensitivity to the peripheral vasculature. ARF was
      induced in Sprague-Dawley rats by 45 min of bilateral renal ischemia and
      reperfusion. Animals were allowed to recover renal structure and function for 5-8
      wk, after which the acute pressor responses to ANG II were evaluated either in
      vivo in in situ skeletal muscle arterioles or in isolated gracilis muscle
      arteries in vitro. Baseline arterial pressure was not different in ARF rats vs.
      sham-operated controls, although ARF rats exhibited an enhanced pressor response
      to bolus ANG II infusion compared with control rats. Steady-state plasma ANG II
      concentration and plasma renin activity were similar between ARF and control
      rats. Constrictor reactivity of in situ cremasteric arterioles from ARF rats was
      enhanced in response to increasing concentrations of ANG II; however, no
      difference was observed in arteriolar responses to elevated PO2, norepinephrine,
      acetylcholine, or sodium nitroprusside. Isolated gracilis muscle arteries from
      ARF rats also showed increased vasoconstriction in response to ANG II but not
      norepinephrine. In conclusion, recovery from ischemic ARF is not associated with
      hypertension but is associated with increased arteriolar constrictor reactivity
      to ANG II. Although the mechanisms of this altered responsiveness are unclear,
      such changes may relate, in part, to cardiovascular complications in patients
      with ARF and/or after renal transplant.

PMID- 16099827
TI  - Decoupled taxonomic radiation and ecological expansion of open-habitat grasses in
      the Cenozoic of North America.
AB  - Because of a dearth of Cenozoic grass fossils, the timing of the taxonomic
      diversification of modern subclades within the grass family (Poaceae) and the
      rise to ecological dominance of open-habitat grasses remain obscure. Here, I
      present data from 99 Eocene to Miocene phytolith assemblages from the North
      American continental interior (Colorado, Nebraska, Wyoming, and Montana/Idaho),
      constituting the only high-resolution mid-Cenozoic record of grasses. Analyses of
      these assemblages show that open-habitat grasses had undergone considerable
      taxonomic diversification by the earliest Oligocene (34 million years ago) but
      that they did not become ecologically dominant in North America until 7-11
      million years later (Late Oligocene or Early Miocene). This pattern of decoupling
      suggests that environmental changes (e.g., climate changes), rather than
      taxonomic radiations within Poaceae, provided the key opportunity for open
      habitat grasses to expand in North America.

PMID- 16099828
TI  - Loss and gain of chromosome 5 controls growth of Candida albicans on sorbose due
      to dispersed redundant negative regulators.
AB  - A reversible decrease or increase of Candida albicans chromosome copy number was
      found to be a prevalent means of survival of this opportunistic pathogen, under
      conditions that kill cells or inhibit their propagation. The utilization of a
      secondary carbon source, l-sorbose, by reversible loss of chromosome 5, serves as
      a model system. We have determined that an approximately 209-kbp portion of the
      right arm of chromosome 5 contains at least five spatially separated,
      functionally redundant regions that control utilization of l-sorbose. The regions
      bear no structural similarity among themselves, and four of them contain
      sequences that bear no similarity with any known sequence. We identified a
      regulatory gene in region A that encodes a helix-loop-helix protein. Most
      important, the multiple redundant regulators scattered along chromosome 5
      explain, in a simple, elegant way, why the loss of the entire homologue is
      usually required for growth on sorbose. Thus, an entire chromosome acts as a
      single regulatory unit, a feature not previously considered. Our finding appears
      to be a paradigm for the control of other phenotypes in C. albicans that also
      depend on chromosome loss, thus implying that C. albicans genes are not
      distributed randomly among different chromosomes.

PMID- 16099829
TI  - Structural determinants of agonist-specific kinetics at the ionotropic glutamate
      receptor 2.
AB  - Glutamate receptors (GluRs) are the most abundant mediators of the fast
      excitatory neurotransmission in the human brain. Agonists will, after activation
      of the receptors, induce different degrees of desensitization. The efficacy of
      agonists strongly correlates with the agonist-induced closure of the ligand
      binding domain. However, the differences in desensitization properties are less
      well understood. By using high-resolution x-ray structure of the GluR2 flop
      (GluR2o) ligand-binding core protein in complex with the partial glutamate
      receptor agonist (S)-2-amino-3-(3-hydroxy-5-tert-butyl-4-isothiazolyl)propionic
      acid [(S)-thio-ATPA], we show that (S)-thio-ATPA induces an 18 degrees closure of
      the binding core similar to another partial agonist, (S)-2-amino-3-(4-bromo-3
      hydroxy-5-isoxazolyl)propionic acid [(S)-Br-HIBO]. Despite the similar closure of
      the ligand-binding domain, we find in electrophysiological studies that (S)-thio
      ATPA induced a 6.4-fold larger steady-state current than (RS)-Br-HIBO, and rapid
      agonist applications show that (S)-thio-ATPA induces a 3.6-fold higher steady
      state/peak ratio and a 2.2-fold slower desensitization time constant than (RS)-Br
      HIBO. Structural comparisons reveal that (S)-Br-HIBO, but not (S)-thio-ATPA,
      induces a twist of the ligand-binding core compared with the apostructure, and
      the agonist-specific conformation of Leu-650 correlates with the different
      kinetic profiles pointing at a key role in defining the desensitization kinetics.
      We conclude that, especially for intermediate efficacious agonists, the
      desensitization properties are influenced by additional ligand-induced factors
      beyond domain closure.

PMID- 16099830
TI  - Arrestin-related proteins mediate pH signaling in fungi.
AB  - Metazoan arrestins bind to seven-transmembrane (7TM) receptors to regulate
      function. Aspergillus nidulans PalF, a protein involved in the fungal ambient pH
      signaling pathway, contains arrestin N-terminal and C-terminal domains and binds
      strongly to two different regions within the C-terminal cytoplasmic tail of the
      7TM, putative pH sensor PalH. Upon exposure to alkaline ambient pH, PalF is
      phosphorylated and, like mammalian beta-arrestins, ubiquitinated in a signal
      dependent and 7TM protein-dependent manner. Substitution in PalF of a highly
      conserved arrestin N-terminal domain Ser residue prevents PalF-PalH interaction
      and pH signaling in vivo. Thus, PalF is the first experimentally documented
      fungal arrestin-related protein, dispelling the notion that arrestins are
      restricted to animal proteomes. Epistasis analyses demonstrate that PalF
      posttranslational modification is partially dependent on the 4TM protein PalI but
      independent of the remaining pH signal transduction pathway proteins PalA, PalB,
      and PalC, yielding experimental evidence bearing on the order of participation of
      the six components of the pH signal transduction pathway. Our data strongly
      implicate PalH as an ambient pH sensor, possibly with the cooperation of PalI.

PMID- 16099831
TI  - Neuronal ELAV proteins enhance mRNA stability by a PKCalpha-dependent pathway.
AB  - More than 1 in 20 human genes bear in the mRNA 3' UTR a specific motif called the
      adenine- and uridine-rich element (ARE), which posttranscriptionally determines
      its expression in response to cell environmental signals. ELAV (embryonic lethal
      abnormal vision) proteins are the only known ARE-binding factors that are able to
      stabilize the bound mRNAs, thereby positively controlling gene expression. Here,
      we show that in human neuroblastoma SH-SY5Y cells, neuron-specific ELAV (nELAV)
      proteins (HuB, HuC, and HuD) are up-regulated and redistributed by 15 min of
      treatment with the activators of PKC phorbol esters and bryostatin-1. PKC
      stimulation also induces nELAV proteins to colocalize with the translocated
      PKCalpha isozyme preferentially on the cytoskeleton, with a concomitant increase
      of nELAV threonine phosphorylation. The same treatment promotes stabilization of
      growth-associated protein 43 (GAP-43) mRNA, a well known nELAV target, and
      induces an early increase in GAP-43 protein concentration, again only in the
      cytoskeletal cell fraction. Genetic or pharmacological inactivation of PKCalpha
      abolishes nELAV protein cytoskeletal up-regulation, GAP-43 mRNA stabilization,
      and GAP-43 protein increase, demonstrating the primary role of this specific PKC
      isozyme in the cascade of nELAV recruitment. Finally, in vivo PKC activation is
      associated with an up-regulation of nELAV proteins in the hippocampal rat brain.
      These findings suggest a model for gene expression regulation by nELAV proteins
      through a PKCalpha-dependent pathway that is relevant for the cellular programs
      in which ARE-mediated control plays a pivotal role.

PMID- 16099832
TI  - Higher-order thalamic relays burst more than first-order relays.
AB  - There is a strong correlation between the behavior of an animal and the firing
      mode (burst or tonic) of thalamic relay neurons. Certain differences between
      first- and higher-order thalamic relays (which relay peripheral information to
      the cortex versus information from one cortical area to another, respectively)
      suggest that more bursting might occur in the higher-order relays. Accordingly,
      we recorded bursting behavior in single cells from awake, behaving rhesus monkeys
      in first-order (the lateral geniculate nucleus, the ventral posterior nucleus,
      and the ventral portion of the medial geniculate nucleus) and higher-order
      (pulvinar and the medial dorsal nucleus) thalamic relays. We found that the
      extent of bursting was dramatically greater in the higher-order than in the first
      order relays, and this increased bursting correlated with lower spontaneous
      activity in the higher-order relays. If bursting effectively signals the
      introduction of new information to a cortical area, as suggested, this increased
      bursting may be more important in corticocortical transmission than in
      transmission of primary information to cortex.

PMID- 16099833
TI  - MicroRNAs acting in a double-negative feedback loop to control a neuronal cell
      fate decision.
AB  - The elucidation of the architecture of gene regulatory networks that control cell
      type specific gene expression programs represents a major challenge in
      developmental biology. We describe here a cell fate decision between two
      alternative neuronal fates and the architecture of a gene regulatory network that
      controls this cell fate decision. The two Caenorhabditis elegans taste receptor
      neurons "ASE left" (ASEL) and "ASE right" (ASER) share many bilaterally symmetric
      features, but each cell expresses a distinct set of chemoreceptors that endow the
      gustatory system with the capacity to sense and discriminate specific
      environmental inputs. We show that these left/right asymmetric fates develop from
      a precursor state in which both ASE neurons express equivalent features. This
      hybrid precursor state is unstable and transitions into the stable ASEL or ASER
      terminal end state. Although this transition is spatially stereotyped in wild
      type animals, mutant analysis reveals that each cell has the potential to
      transition into either the ASEL or ASER stable end state. The stability and
      irreversibility of the terminal differentiated state is ensured by the
      interactions of two microRNAs (miRNAs) and their transcription factor targets in
      a double-negative feedback loop. Simple feedback loops are found as common motifs
      in many gene regulatory networks, but the loop described here is unusually
      complex and involves miRNAs. The interaction of miRNAs in double-negative
      feedback loops may not only be a means for miRNAs to regulate their own
      expression but may also represent a general paradigm for how terminal cell fates
      are selected and stabilized.

PMID- 16099834
TI  - Characterization of Dicer-deficient murine embryonic stem cells.
AB  - Dicer is an RNase III-family nuclease that initiates RNA interference (RNAi) and
      related phenomena by generation of the small RNAs that determine the specificity
      of these gene silencing pathways. We have previously shown that Dicer is
      essential for mammalian development, with Dicer-deficient mice dying at embryonic
      day 7.5 with a lack of detectable multipotent stem cells. To permit a more
      detailed investigation of the biological roles of Dicer, we have generated
      embryonic stem cell lines in which their single Dicer gene can be conditionally
      inactivated. As expected, Dicer loss compromises maturation of microRNAs and
      leads to a defect in gene silencing triggered by long dsRNAs. However, the
      absence of Dicer does not affect the ability of small interfering RNAs to repress
      gene expression. Of interest, Dicer loss does compromise the proliferation of ES
      cells, possibly rationalizing the phenotype previously observed in Dicer-null
      animals. Dicer loss also affects the abundance of transcripts from mammalian
      centromeres but does so without a pronounced affect on histone modification
      status at pericentric repeats or methylation of centromeric DNA. These studies
      provide a conditional model of RNAi deficiency in mammals that will permit the
      dissection of the biological roles of the RNAi machinery in cultured mammalian
      cells.

PMID- 16099835
TI  - Genetic ablation of Cyclin D1 abrogates genesis of rhabdoid tumors resulting from
      Ini1 loss.
AB  - Rhabdoid tumors are aggressive pediatric malignancies for which, currently, there
      are no effective or standard treatment strategies. Rhabdoid tumors arise because
      of the loss of the tumor suppressor gene INI1. We have previously demonstrated
      that INI1 represses Cyclin D1 transcription in rhabdoid cells by directly
      recruiting histone deacetylase 1 complex to its promoter, leading to G(0)-G(1)
      arrest. Expression of Cyclin D1 overcomes cell cycle arrest mediated by INI1 and
      Cyclin D1 overexpression in human rhabdoid tumors is a common phenomenon.
      However, it is not clear whether Cyclin D1 is a critical downstream target of
      INI1 in vivo and whether the derepression of this gene is essential for rhabdoid
      tumorigenesis. To determine the requirement of Cyclin D1 for genesis of rhabdoid
      tumors in vivo, we developed Ini1 heterozygous mice by targeted disruption. We
      found that the tumors developed in these Ini1+/- mice are rhabdoid, defective for
      Ini1 protein, and like the human tumors, express Cyclin D1. We crossed Ini1+/-
      mice to Cyclin D1-/- mice and found that Ini1+/- mice with Cyclin D1 deficiency
      did not develop any spontaneous tumors, in contrast to the parental Ini1+/- mice.
      These results strongly support the hypothesis that Cyclin D1 is a key mediator in
      the genesis of rhabdoid tumors. Our results provide an in vivo proof of concept
      that drugs that target Cyclin D1 expression or activity could be potentially
      effective as novel therapeutic agents for rhabdoid tumors.

PMID- 16099836
TI  - Bacterial genome size reduction by experimental evolution.
AB  - Bacterial evolution toward endosymbiosis with eukaryotic cells is associated with
      extensive bacterial genome reduction and loss of metabolic and regulatory
      capabilities. Here we examined the rate and process of genome reduction in the
      bacterium Salmonella enterica by a serial passage experimental evolution
      procedure. The initial rate of DNA loss was estimated to be 0.05 bp per
      chromosome per generation for a WT bacterium and approximately 50-fold higher for
      a mutS mutant defective in methyl-directed DNA mismatch repair. The endpoints
      were identified for seven chromosomal deletions isolated during serial passage
      and in two separate genetic selections. Deletions ranged in size from 1 to 202
      kb, and most of them were not associated with DNA repeats, indicating that they
      were formed via RecA-independent recombination events. These results suggest that
      extensive genome reduction can occur on a short evolutionary time scale and that
      RecA-dependent homologous recombination only plays a limited role in this process
      of jettisoning superfluous DNA.

PMID- 16099837
TI  - Differential patterns of apoptosis in response to aging in Drosophila.
AB  - Several lines of evidence suggest that programmed cell death may play a role in
      the aging process and the age-related functional declines of multicellular
      organisms. To pave the way for the use of Drosophila to rigorously test this
      hypothesis in a genetic model organism, this work examines the pattern of
      apoptosis in the adult fly during aging. The analysis across the lifespan of
      caspase activity and DNA fragmentation shows that apoptosis occurs in adult flies
      at all ages and that it is linked to physiological age. The results establish
      that under normal conditions, fly aging is coupled with a lifelong gradual
      increase of apoptosis within muscle cells and an activation of apoptosis in fat
      cells of old flies. The nervous system does not show signs of apoptosis. These
      time- and tissue-specific changes indicate that aging influences the levels and
      the nature of the cells that commit to apoptosis. The comparison with the
      apoptotic response to starvation and oxidative stresses strongly suggests that
      the lifelong increase in flight and leg muscles results from the accumulation of
      oxidative damage associated with aging. This finding presents an attractive
      mechanism to account for the decline of locomotor functions and muscle loss in
      the elderly and opens the way for the genetic analysis of sarcopenia in
      Drosophila.

PMID- 16099838
TI  - Targets of microRNA regulation in the Drosophila oocyte proteome.
AB  - MicroRNAs (miRNAs) are a class of small RNAs that silence gene expression. In
      animal cells, miRNAs bind to the 3' untranslated regions of specific mRNAs and
      inhibit their translation. Although some targets of a handful of miRNAs are
      known, the number and identities of mRNA targets in the genome are uncertain, as
      are the developmental functions of miRNA regulation. To identify the global range
      of miRNA-regulated genes during oocyte maturation of Drosophila, we compared the
      proteome from wild-type oocytes with the proteome from oocytes lacking the dicer
      1 gene, which is essential for biogenesis of miRNAs. Most identified proteins
      appeared to be subject to translation inhibition. Their transcripts contained
      putative binding sites in the 3' untranslated region for a subset of miRNAs,
      based on computer modeling. The fraction of genes subject to direct and indirect
      repression by miRNAs during oocyte maturation appears to be small (4%), and the
      genes tend to share a common functional relationship in protein biogenesis and
      turnover. The preponderance of genes that control global protein abundance
      suggests this process is under tight control by miRNAs at the onset of
      fertilization.

PMID- 16099839
TI  - Interaction of organic cations with a newly identified plasma membrane monoamine
      transporter.
AB  - Many endogenous compounds and xenobiotics are organic cations that rely on
      polyspecific organic cation transporters (OCTs) to traverse cell membranes. We
      recently cloned a novel human plasma membrane monoamine transporter (PMAT) that
      belongs to the equillibrative nucleoside transporter (ENT) family. We have
      reported previously that, unlike other ENTs, PMAT (also known as ENT4) is a Na+
      independent and membrane potential-sensitive transporter that transports
      monoamine neurotransmitters and the neurotoxin 1-methyl-4-phenylpyridinium
      (MPP+). These compounds are the known substrates for OCTs, which raises the
      possibility that PMAT functions as a polyspecific transporter like the OCTs. In
      the present study, we analyzed the interaction of PMAT with a series of
      structurally diverse organic cations using MDCK cells stably expressing human
      PMAT. Our study showed that PMAT interacts with many organic cations that have
      heterogeneous chemical structures. PMAT transports classic OCT substrates, such
      as tetraethylammonium, guanidine, and histamine. Prototype OCT inhibitors,
      including cimetidine, and type II cations (e.g., quinidine, quinine, verapamil,
      and rhodamine123) are also PMAT inhibitors. An analysis of molecular structures
      and apparent binding affinities revealed that charge and hydrophobicity are the
      principal determinants for transporter-substrate/inhibitor interaction. A planar
      aromatic mass seems to be important for high affinity interaction. trans
      Stimulation and efflux studies demonstrate that PMAT is able to mediate
      bidirectional transport. These functional properties of PMAT are strikingly
      similar to those of the OCTs. We therefore conclude that PMAT can function as a
      polyspecific organic cation transporter, which may play a role in organic cation
      transport in vivo.

PMID- 16099840
TI  - Characterization of determinants of ligand binding to the nicotinic acid receptor
      GPR109A (HM74A/PUMA-G).
AB  - The G-protein-coupled receptor GPR109A (HM74A/PUMA-G) has recently been shown to
      function as a receptor for nicotinic acid (niacin) and to mediate its
      antilipolytic effects. Nicotinic acid is able to strongly raise plasma levels of
      high-density lipoprotein cholesterol, a property that distinguishes nicotinic
      acid from other lipid-lowering drugs. To investigate the structural determinants
      of GPR109A ligand binding, we performed site-directed mutagenesis of putative
      ligand binding residues combined with generation of chimeric receptors consisting
      of GPR109A and its close relative GPR109B, which does not bind nicotinic acid. We
      could identify Asn86/Trp91 [transmembrane helix (TMH) 2/extracellular loop (ECL)
      1], Arg111 (TMH3), Ser178 (ECL2), Phe276 (TMH7), and Tyr284 (TMH7) as amino acid
      residues critical for binding of nicotinic acid. Together with data from
      molecular modeling studies, our data suggest that the ligand binding pocket for
      nicotinic acid of GPR109A is distinct from that of most other group A receptors.
      Although Arg111 at TMH3 serves as the basic anchor point for the carboxylate
      ligands, the ring system of nicotinic acid is embedded between Trp91 at the
      junction TMH2/ECL1 and Phe276/Tyr284 at TMH7. The heterocyclic ring is also bound
      to Ser178 at ECL2 via an H-bond. These data will facilitate the design of new
      antidyslipidemic drugs acting via GPR109A.

PMID- 16099841
TI  - Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of
      effector memory T cells in autoimmune diseases.
AB  - The lymphocyte K+ channel Kv1.3 constitutes an attractive pharmacological target
      for the selective suppression of terminally differentiated effector memory T
      (TEM) cells in T cell-mediated autoimmune diseases, such as multiple sclerosis
      and type 1 diabetes. Unfortunately, none of the existing small-molecule Kv1.3
      blockers is selective, and many of them, such as correolide, 4-phenyl-4-[3
      (methoxyphenyl)-3-oxo-2-azapropyl]cyclohexanone, and our own compound Psora-4
      inhibit the cardiac K+ channel Kv1.5. By further exploring the structure-activity
      relationship around Psora-4 through a combination of traditional medicinal
      chemistry and whole-cell patch-clamp, we identified a series of new
      phenoxyalkoxypsoralens that exhibit 2- to 50-fold selectivity for Kv1.3 over
      Kv1.5, depending on their exact substitution pattern. The most potent and "drug
      like" compound of this series, 5-(4-phenoxybutoxy)psoralen (PAP-1), blocks Kv1.3
      in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by
      preferentially binding to the C-type inactivated state of the channel. PAP-1 is
      23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family
      channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG,
      calcium-activated K+ channels, Na+,Ca2+, and Cl- channels. PAP-1 does not exhibit
      cytotoxic or phototoxic effects, is negative in the Ames test, and affects
      cytochrome P450-dependent enzymes only at micromolar concentrations. PAP-1
      potently inhibits the proliferation of human TEM cells and suppresses delayed
      type hypersensitivity, a TEM cell-mediated reaction, in rats. PAP-1 and several
      of its derivatives therefore constitute excellent new tools to further explore
      Kv1.3 as a target for immunosuppression and could potentially be developed into
      orally available immunomodulators.

PMID- 16099842
TI  - Presynaptic inhibition via a phospholipase C- and phosphatidylinositol
      bisphosphate-dependent regulation of neuronal Ca2+ channels.
AB  - Presynaptic inhibition of transmitter release is commonly mediated by a direct
      interaction between G protein betagamma subunits and voltage-activated Ca2+
      channels. To search for an alternative pathway, the mechanisms by which
      presynaptic bradykinin receptors mediate an inhibition of noradrenaline release
      from rat superior cervical ganglion neurons were investigated. The peptide
      reduced noradrenaline release triggered by K+-depolarization but not that evoked
      by ATP, with Ca2+ channels being blocked by Cd2+. Bradykinin also reduced Ca2+
      current amplitudes measured at neuronal somata, and this effect was pertussis
      toxin-insensitive, voltage-independent, and developed slowly within 1 min. The
      inhibition of Ca2+ currents was abolished by a phospholipase C inhibitor, but it
      was not altered by a phospholipase A2 inhibitor, by the depletion of
      intracellular Ca2+ stores, or by the inactivation of protein kinase C or Rho
      proteins. In whole-cell recordings, the reduction of Ca2+ currents was
      irreversible but became reversible when 4 mM ATP or 0.2 mM dioctanoyl
      phosphatidylinositol-4,5-bisphosphate was included in the pipette solution. In
      contrast, the effect of bradykinin was entirely reversible in perforated-patch
      recordings but became irreversible when the resynthesis of phosphatidylinositol
      4,5-bisphosphate was blocked. Thus, the inhibition of Ca2+ currents by bradykinin
      involved a consumption of phosphatidylinositol-4,5-bisphosphate by phospholipase
      C but no downstream effectors of this enzyme. The reduction of noradrenaline
      release by bradykinin was also abolished by the inhibition of phospholipase C or
      of the resynthesis of phosphatidylinositol-4,5-bisphosphate. These results show
      that the presynaptic inhibition was mediated by a closure of voltage-gated Ca2+
      channels through depletion of membrane phosphatidylinositol bisphosphates via
      phospholipase C.

PMID- 16099843
TI  - Retinoid X receptor-alpha-dependent transactivation by a naturally occurring
      structural variant of human constitutive androstane receptor (NR1I3).
AB  - The constitutive androstane receptor (CAR) mediates the hepatic induction of
      various xenobiotic metabolizing enzymes and transporters after specific chemical
      exposures. Recent reports have established the existence of several human CAR
      mRNA splice variants, including a prominently expressed form termed CAR3, a
      receptor that possesses a 5 amino acid insertion within its ligand binding
      domain. In this study, we demonstrate that, in contrast to the constitutively
      active reference form of the receptor, CAR3 is ligand-activated, transactivating
      an optimized DR-4 x 3 reporter in response to the human CAR ligand 6-(4
      chlorophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde O-(3, 4-dichlorobenzyl)oxime
      (CITCO). The transactivation response requires the DNA binding domain and AF-2
      motif of CAR3 and is markedly enhanced by retinoid X receptor-alpha (RXR)
      cotransfection. The stimulatory effects of RXR involve a unique mechanism,
      because they were completely dependent on the RXR AF-2 function but independent
      of both the RXR A/B domain and its C domain/heterodimerization region. Mammalian
      two-hybrid results demonstrated that RXR enhanced CITCO-dependent interaction of
      CAR3 with the receptor interaction domain of SRC-1, indicating that RXR augments
      CAR3 activity by facilitating coactivator recruitment. It is noteworthy that
      clotrimazole also functions as a ligand activator of CAR3, in contrast to the
      inverse agonist activity exhibited by this agent on the reference form of the
      receptor. Furthermore, results of transfection assays reveal that CAR3 is capable
      of transactivating the natural CYP2B6 and CYP3A4 gene enhancers, exhibiting both
      ligand- and RXR-dependence. These results demonstrate that CAR3, unlike CAR1, is
      a ligand-activated receptor and that CAR3 may regulate gene expression in vivo in
      a manner distinct from the reference form of the receptor.

PMID- 16099844
TI  - Live long and prosper.
AB  - In this issue of Molecular Pharmacology, Meyn et al. (p. 1320) provide the
      results of the first comprehensive investigation of the expression pattern of the
      Src family of nonreceptor tyrosine kinases (SFK) in mouse embryonic stem (ES)
      cells. They found that self-renewing ES cells express seven of the eight
      mammalian SFK members and that some undergo distinct expression changes during
      early differentiation events. One of the most dramatic changes was in Hck
      transcript levels, which decreased almost 30-fold during the first 3 days of
      embryoid body formation, a culture system model of early embryogenesis and
      differentiation. Other SFKs, such as Fyn and Src, remain present and active as ES
      cells differentiate. Of particular interest was the observation that ES cell self
      renewal or differentiation can be manipulated through the selective
      pharmacological inhibition of SFK members. This information should help in the
      expanding efforts to exploit ES cells for basic and clinical purposes.

PMID- 16099845
TI  - Alkylation of beta-tubulin on Glu 198 by a microtubule disrupter.
AB  - We have shown that beta-tubulin was alkylated by a microtubule disrupter, N-4
      iodophenyl-N'-(2-chloroethyl)urea (ICEU), on a glutamic acid residue at position
      198 and not on the previously proposed reactive cysteine 239. ICEU belongs to the
      4-substituted-phenyl-N'-(2-chloroethyl) urea class that alkylates mainly cellular
      proteins. Previous studies have shown that the tert-butyl (tBCEU) and iodo (ICEU)
      derivatives induce microtubule disruption because of beta-tubulin alkylation.
      tBCEU was supposed to bind covalently to cysteine 239 of beta-tubulin, but this
      binding site was not clearly confirmed (Cancer Res 60:985-992, 2000). We have
      isolated and analyzed beta-tubulin after two-dimensional gel electrophoresis of
      proteins from B16 cells incubated with ICEU. Alkylated beta-tubulin had a lower
      apparent molecular weight and a more basic isoelectric point than the unmodified
      protein. Labeled N-4-[125I]CEU was effectively bound to the modified beta-tubulin
      but using matrix-assisted laser desorption ionization/time-of-flight mass
      spectrometry, we demonstrated that none of the cysteine residues of beta-tubulin
      was linked to the alkylating agent. In contrast, peptide masses at m/z 4883 and
      1792 in trypsin or Asp-N digestions of beta-tubulin confirmed binding of
      iodophenylethylureido moiety to peptides [175-213] or [197-208] respectively.
      Fragmentation analyses by electrospray mass spectrometry using triply charged
      ions of peptide [175-213] identified a glutamic acid at position 198 as target
      for alkylation via an ester bond with ICEU. This amino acid located in the
      intermediate domain of the beta-tubulin should play an essential role in the
      conformational structure necessary for the interaction between dimers in the
      protofilament.

PMID- 16099846
TI  - Protein PEGylation decreases observed target association rates via a dual
      blocking mechanism.
AB  - PEGylation is an attractive strategy to enhance the therapeutic efficacy of
      proteins with a short serum half-life. It can be used to extend the serum
      persistence and to reduce the immunogenicity of proteins. However, PEGylation can
      also lead to a decrease in the functional activity of the molecule to which it is
      applied. We constructed site-specifically PEGylated variants of anti-p185(HER-2)
      antibody fragments in the format of a monovalent single-chain variable fragment
      and a divalent miniantibody and characterized the antigen binding properties in
      detail. Mass-transport limited BIAcore measurements and binding assays on HER-2
      overexpressing cells demonstrated that the immunoreactivity of the antibody
      fragments is fully maintained after PEGylation. Nevertheless, we found that the
      attachment of a 20-kDa polyethylene glycol (PEG) moiety led to a reduction in
      apparent affinity of approximately 5-fold, although in both formats, the
      attachment site was most distal to the antigen binding regions. This decrease in
      affinity was observed in kinetic BIAcore measurements as well as in equilibrium
      binding assays on whole cells. By analysis of the binding kinetics, we could
      pinpoint this reduction exclusively to slower apparent on rates. Through both
      experimental and computational analyses, we demonstrate that these reduced on
      rates do not arise from diffusion limitations. We show that a mathematical model
      accounting for both intramolecular and intermolecular blocking mechanisms of the
      PEG moiety can robustly explain the observed binding kinetics. The results
      suggest that PEGylation can significantly alter the binding-competent fraction of
      both ligands and receptors and may help to explain some of the beneficial effects
      of PEGylation in vivo.

PMID- 16099847
TI  - Role of the redox protein thioredoxin in cytoprotective mechanism evoked by (-)
      deprenyl.
AB  - Through the inhibition of monoamine oxidase type B (MAO-B), (-)-deprenyl
      (selegiline) prevents the conversion of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) to the toxic metabolite 1-methyl-4-phenylpyridinium ion
      (MPP+) and also prevents the neurotoxicity in the dopaminergic neurons in animal
      models. Cumulative observations suggest that selegiline may also protect against
      MPP+-induced neurotoxicity, possibly through the induction of pro-survival genes.
      We have observed that thioredoxin (Trx) mediates the induction of mitochondrial
      manganese superoxide dismutase (MnSOD) and Bcl-2 during preconditioning-induced
      hormesis. We therefore investigated whether the redox protein Trx plays any role
      in the neuroprotective mechanism of selegiline against MPP+-induced cytotoxicity
      in human SH-SY5Y neuroblastoma cells and also in primary neuronal cultures of
      mouse midbrain dopaminergic neurons. After confirming that selegiline protects
      against MPP+-induced cytotoxicity, we observed further that selegiline, at 1
      microM or less, induced Trx for protection against oxidative injury caused by
      MPP+. The induction of Trx was blocked by protein kinase A (PKA) inhibitor and
      mediated by a PKA-sensitive phospho-activation of mitogen-activated protein (MAP)
      kinase Erk1/2 and the transcription factor c-Myc. Selegiline-induced Trx and
      associated neuroprotection were concomitantly blocked by the antisense against
      Trx mRNA, but not the sense or antisense mutant phosphothionate oligonucleotides,
      not only in human SH-SY5Y cells but also in mouse primary neuronal culture of
      midbrain dopaminergic neurons. Furthermore, the redox cycling of Trx may mediate
      the protective action of selegiline because the inhibition of Trx reductase by 1
      chloro-2,4-dinitrobenzene ameliorated the effect of selegiline. Trx (1 microM)
      consistently increased the expression of mitochondrial proteins MnSOD and Bcl-2,
      supporting cell survival (Andoh et al., 2002). In conclusion, without modifying
      MAO-B activity, selegiline augments the gene induction of Trx, leading to
      elevated expression of antioxidative MnSOD and antiapoptotic Bcl-2 proteins for
      protecting against MPP+-induced neurotoxicity.

PMID- 16099849
TI  - Abstracts of the 7th International Symposium on Mass Spectrometry in the Health
      and Life Sciences: Molecular and Cellular Proteomics, August 21-25, 2005, San
      Francisco, CA, USA.

PMID- 16099848
TI  - Blue native/SDS-PAGE analysis reveals reduced expression of the mClCA3 protein in
      cystic fibrosis knock-out mice.
AB  - Cystic fibrosis (CF) is a frequent autosomal recessive disorder caused by
      mutation of a gene encoding a multifunctional transmembrane protein, the cystic
      fibrosis transmembrane conductance regulator (CFTR), located in the apical
      membrane of epithelial cells lining exocrine glands. In an attempt to get a more
      complete picture of the pleiotropic effects of the CFTR defect on epithelial
      cells and particularly on the membrane compartment, a bidimensional blue native
      (BN)/SDS-PAGE-based proteomic approach was used on colonic crypt samples from
      control and CFTR knock-out mice (cftr-/-). This approach overcomes the
      difficulties of membrane protein analysis by conventional two-dimensional PAGE
      and is able to resolve multiprotein complexes. Used here for the first time on
      crude membrane proteins that were extracted from murine colonic crypts, BN/SDS
      PAGE allows effective separation of protein species and complexes of various
      origins, including mitochondria, plasma membrane, and intracellular compartments.
      The major statistically significant difference in protein maps obtained with
      samples from control and cftr-/- mice was unambiguously identified as mClCA3, a
      member of a family of calcium-activated chloride channels considered to be key
      molecules in mucus secretion by goblet cells. On the basis of this finding, we
      evaluated the overall expression and localization of mClCA3 in the colonic
      epithelium and in the lung of mice by immunoblot analysis and
      immunohistochemistry. We found that mClCA3 expression was significantly decreased
      in the colon and lung of the cftr-/- mice. In an ex vivo assay, we found that the
      Ca2+-dependent (carbachol-stimulated) glycoprotein secretion strongly inhibited
      by the calcium-activated chloride channel blocker niflumic acid (100 microm) was
      impaired in the distal colon of cftr-/- mice. These results support the
      conclusion that a ClCA-related function in the CF colon depends on CFTR
      expression and may be correlated with the impaired expression of mClCA3.

PMID- 16099850
TI  - Childhood overweight and maturational timing in the development of adult
      overweight and fatness: the Newton Girls Study and its follow-up.
AB  - OBJECTIVE: Although several studies have suggested that early menarche is
      associated with the development of adult overweight, few have accounted for
      childhood overweight before menarche. STUDY DESIGN: A 30-year follow-up of the
      original participants in the Newton Girls Study, a prospective study of
      development in a cohort of girls followed through menarche, provided data on
      premenarcheal relative weight and overweight (BMI >85th percentile),
      prospectively obtained age at menarche, self-reported adult BMI, overweight (BMI
      > 25), obesity (BMI > 30) and, for a subset of participants, percentage body fat
      by dual-energy x-ray absorptiometry. RESULTS: Of the 448 women who participated
      in the adult follow-up at a mean age of 42.1 years (SD: 0.76 years), 307 had
      childhood data with which to characterize premenarcheal and menarcheal weight
      status and age at menarche. After a follow-up of 30.1 years (SD: 1.4 years),
      reported BMI was 23.4 (4.8), 28% were overweight, and 9% were obese. In
      multivariate linear and logistic-regression analyses, almost all of the influence
      on adult weight status was a result of premenarcheal weight status (model R2 =
      0.199). Inclusion of a variable to reflect menarcheal timing provided very little
      additional information (model R2 = 0.208). Girls who were overweight before
      menarche were 7.7 times more likely to be overweight as adults (95% confidence
      interval: 2.3, 25.8), whereas early menarche (at < or = 12 years of age) did not
      elevate risk (odds ratio: 1.3, 95% confidence interval: 0.66, 2.43). A similar
      pattern of results was observed when percentage body fat in adulthood was
      evaluated. CONCLUSIONS: The apparent influence of early maturation on adult
      female overweight is largely a result of the influence of elevated relative
      weight on early maturation. Interventions to prevent and treat overweight should
      focus on girls before they begin puberty.

PMID- 16099851
TI  - Serum biomarkers for identifying acute chest syndrome among patients who have
      sickle cell disease and present to the emergency department.
AB  - OBJECTIVE: To compare the accuracy of biomarkers for identifying acute chest
      syndrome (ACS) in patients with sickle cell disease presenting to a pediatric
      emergency department (ED). METHODS: We conducted a 13-month-long (2002-2003)
      cohort study with nested case-control in patients with sickle cell disease
      presenting to the pediatric ED with vaso-occlusive crises or fever in which we
      compared levels of secretory phospholipase A2 (sPLA2), endothelin-1, interleukin
      6 (IL-6), and peripheral white blood cell count (WBC) in cases that were
      complicated by ACS and in control subjects with uncomplicated illnesses. For
      diagnosis, a test was considered to be accurate when the area under its receiver
      operator characteristic curve (AUC) was >0.70. Laboratory tests with AUC values >
      or =0.70 were entered into a binary recursive partitioning model for diagnosis.
      RESULTS: For the period of study, samples from 72 visits were obtained from 51
      patients who presented with vaso-occlusive crises (range: 1-4 visits per patient;
      15 were enrolled more than once). ACS complicated 19 of 72 visits (26%, 95%
      confidence interval: 17%-38%). At an AUC value of 0.79, only the sPLA2 test was
      accurate for diagnosing ACS. AUC values for peripheral WBC, endothelin-1, and IL
      6 were 0.68, 0.51, and 0.52, respectively. Binary recursive partitioning retained
      only sPLA2 at a cutoff of 13.7 ng/mL to be accurate for diagnosis. This cutoff
      had a sensitivity of 74% (14 of 19), a specificity of 87% (46 of 53), a positive
      likelihood ratio of 5.6, and a negative likelihood ratio of 0.18. CONCLUSIONS:
      Secretory phospholipase A2 but not endothelin-1, IL-6, or WBC is an accurate test
      for identifying present or incipient ACS in young patients who present to the ED
      with sickle cell pain crises.

PMID- 16099852
TI  - Asymptomatic inflammatory bowel disease presenting with mucocutaneous findings.
AB  - Although inflammatory bowel disease (IBD) typically presents with
      gastrointestinal complaints, mucocutaneous lesions are commonly associated and
      can precede gastrointestinal symptoms, thereby alerting the clinician to the
      diagnosis of IBD before the onset of gastrointestinal symptoms. Nine children are
      reported who had no gastrointestinal symptoms suggestive of IBD but presented
      with mucocutaneous findings of IBD and were subsequently diagnosed with Crohn's
      disease or ulcerative colitis based on characteristic features on
      gastrointestinal endoscopy and/or biopsies. The majority of the patients had oral
      and perianal lesions. We believe that IBD is a common etiology for persistent
      oral lesions in the pediatric population. In addition to a good history, children
      with unexplained oral mucous membrane lesions should have an examination of the
      rectal and genital mucosa as well as tests for complete blood count, iron levels,
      sedimentation rate, albumin, and occult blood in the stool with endoscopy and
      biopsies to rule out IBD if indicated.

PMID- 16099853
TI  - Multiple endocrine neoplasia type 2A in a kindred with C634Y mutation.
AB  - Multiple endocrine neoplasia type 2A (MEN 2A) is most frequently caused by codon
      634 activating mutations. Medullary thyroid carcinoma has occurred before the age
      of 2, with pheochromocytomas and primary hyperparathyroidism occurring later in
      childhood. We report cases of 4 siblings with C634Y-positive MEN 2A (all <11
      years old): 3 with medullary thyroid carcinoma (1 had nodal metastasis, and
      another had a parathyroid adenoma) and 1 with C-cell hyperplasia.

PMID- 16099854
TI  - Changes in expression of hypothalamic releasing hormone receptors in individual
      rat anterior pituitary cells during maturation, puberty and senescence.
AB  - Anterior pituitary (AP) is formed by five different cell types, each one
      producing a different AP hormone whose secretion is regulated by a specific
      hypothalamic-releasing hormone (HRH). On the other hand, a significant number of
      AP cells express multiple HRH receptors (multiresponsive cells). Plastic changes
      in expression of HRH receptors in individual AP cells are involved in critical
      endocrine events. Here we have characterized the changes in functional responses
      to CRH, LHRH, TRH, and GHRH in individual AP cells throughout the whole life span
      of the rat. To this end, calcium responses to the HRHs were followed by single
      cell imaging in freshly dispersed AP cells prepared from rats of different ages
      (0-540 postnatal days). Three different cell pools were identified: 1)
      monoresponsive cells, holding a single class of HRH receptor; 2) multiresponsive
      cells; and 3) nonresponsive cells. The relative abundance of each pool changed
      with age. Nonresponsive cells were abundant at birth, multiresponsive cells were
      abundant at puberty, and monoresponsive cells dominated at senescence. The
      relative abundance of each HRH receptor changed largely with age but not gender.
      In addition, the contribution of monoresponsive and multiresponsive cells to
      responses to each HRH changed very much with age. Thus, the anterior pituitary
      shows large changes in cell populations typed by functional responses to HRHs
      during maturation, puberty, and senescence.

PMID- 16099855
TI  - Cathepsins in the ovine uterus: regulation by pregnancy, progesterone, and
      interferon tau.
AB  - Cathepsins (CTS) are peptidases that have biological roles in degrading
      extracellular matrix, catabolism of intracellular proteins, and processing of
      prohormones. Expression of CTSB, CTSD, CTSH, CTSK, CTSL, CTSS, and CTSZ genes was
      detected in the endometria of cyclic and early pregnant ewes with distinct
      temporal and spatial expression patterns. In the d 18 and 20 conceptus,
      expression of CTSB, CTSD, CTSL, and CTSZ mRNA was detected in the trophectoderm.
      Of particular note, CTSL mRNA was the most abundant CTS mRNA in the ovine
      endometrium and detected only in the luminal epithelium and superficial glandular
      epithelium of cyclic and pregnant ewes. CTSL mRNA increased 8-fold between d 10
      and 18 in endometria of pregnant ewes, whereas it declined between d 14 and 16 in
      cyclic ewes. CTSL protein was also detected in conceptus trophectoderm, and pro
      CTSL was detected in uterine flushings from ewes between d 12 and 16 of
      pregnancy. In ovariectomized and catheterized ewes, CTSL mRNA in the endometrium
      was increased by progesterone and intrauterine injections of ovine interferon
      (IFN)tau. Other endometrial CTS genes were also regulated by progesterone alone
      (CTSB, CTSK, CTSS, and CTSZ) or progesterone and IFNtau (CTSH, CTSK, CTSS, and
      CTSZ). These results indicate that CTS of endometrial and conceptus origin may
      regulate endometrial remodeling and conceptus implantation, endometrial CTS genes
      are regulated by ovarian and placental hormones, and CTSL is a novel IFNtau
      stimulated gene expressed only in luminal epithelium and superficial glandular
      epithelium of the endometrium.

PMID- 16099856
TI  - A mouse model of albright hereditary osteodystrophy generated by targeted
      disruption of exon 1 of the Gnas gene.
AB  - Albright hereditary osteodystrophy is caused by heterozygous inactivating
      mutations in GNAS, a gene that encodes not only the alpha-chain of Gs (Galphas),
      but also NESP55 and XLalphas through use of alternative first exons. Patients
      with GNAS mutations on maternally inherited alleles are resistant to multiple
      hormones such as PTH, TSH, LH/FSH, GHRH, and glucagon, whose receptors are
      coupled to Gs. This variant of Albright hereditary osteodystrophy is termed
      pseudohypoparathyroidism type 1a and is due to presumed tissue-specific paternal
      imprinting of Galphas. Previous studies have shown that mice heterozygous for a
      targeted disruption of exon 2 of Gnas, the murine homolog of GNAS, showed unique
      phenotypes dependent on the parent of origin of the mutated allele. However,
      hormone resistance occurred only when the disrupted gene was maternally
      inherited. Because disruption of exon 2 is predicted to inactivate Galphas as
      well as NESP55 and XLalphas, we created transgenic mice with disruption of exon 1
      to investigate the effects of isolated loss of Galphas. Heterozygous mice that
      inherited the disruption maternally (-m/+) exhibited PTH and TSH resistance,
      whereas those with paternal inheritance (+/-p) had normal hormone responsiveness.
      Heterozygous mice were shorter and, when the disrupted allele was inherited
      maternally, weighed more than wild-type littermates. Galphas protein and mRNA
      expression was consistent with paternal imprinting in the renal cortex and
      thyroid, but there was no imprinting in renal medulla, heart, or adipose. These
      findings confirm the tissue-specific paternal imprinting of GNAS and demonstrate
      that Galphas deficiency alone is sufficient to account for the hormone resistance
      of pseudohypoparathyroidism type 1a.

PMID- 16099857
TI  - Proteasomal proteolysis in the adrenergic induction of arylalkylamine-N
      acetyltransferase in rat pinealocytes.
AB  - In this study, we investigated the effect of proteasomal inhibition on the
      induction of arylalkylamine-N-acetyltransferase (AA-NAT) enzyme in cultured rat
      pinealocytes, using two proteasome inhibitors, MG132 and clastolactacystin beta
      lactone (c-lact). Addition of c-lact or MG132 3 h after norepinephrine (NE)
      stimulation produced a significant increase in AA-NAT protein level and enzyme
      activity. However, when the proteasome inhibitors were added before or together
      with NE, significant reductions of the NE-induced aa-nat mRNA, protein, and
      enzyme activity were observed. A similar inhibitory effect of MG132 on aa-nat
      transcription was observed when cells were stimulated by dibutyryl cAMP,
      indicating an effect distal to a post-cAMP step. The inhibitory effect of MG132
      on adrenergic-induced aa-nat transcription was long lasting because it remained
      effective after 14 h of washout and appeared specific for aa-nat because the
      induction of another adrenergic-regulated gene, MAPK phosphatase-1, by NE was not
      affected. Time-profile studies revealed that the inhibitory effect of MG132 on NE
      stimulated aa-nat induction was detected after 1 h, suggesting accumulation of a
      protein repressor as a possible mechanism of action. This possibility was also
      supported by the finding that the inhibitory effect of c-lact on NE-induced aa
      nat induction was markedly reduced by cycloheximide, a protein synthesis
      inhibitor. Together, these results support an important role of proteasomal
      proteolysis in the adrenergic-mediated induction of aa-nat transcription through
      its effect on a protein repressor.

PMID- 16099858
TI  - Permeation of growth hormone across the blood-brain barrier.
AB  - Exogenous GH can affect central nervous system function when given peripherally
      to animals and as a supplemental therapy to humans. This study tested whether GH
      crosses the blood-brain barrier (BBB) by a specific transport system and found
      that both mice and rats have small but significant uptake of GH into the brain
      without a species difference. Determined by multiple-time regression analysis,
      the blood-to-brain influx transfer constants of 125I-labeled rat GH in mice
      (0.23+/-0.07 microl/g.min) and rats (0.32+/-0.04 microl/g.min) were comparable to
      those of some cytokines of similar size, with a half-time disappearance of 125I
      GH of 3.8-7.6 min in blood. Intact 125I-GH was present in both serum and brain
      homogenate 20 min after iv injection. At this time, about 26.8% of GH in brain
      entered the parenchyma, whereas 10% was entrapped in endothelial cells. Neither
      excess GH nor insulin showed acute modulation of the influx, indicating lack of a
      saturable transport system for GH at the BBB. Binding and cellular uptake studies
      in cultured cerebral microvessel endothelial cells (RBE4) further ruled out the
      presence of high-capacity adsorptive endocytosis. The brain influx of GH by
      simple diffusion adds definitive value to the long-disputed question of whether
      and how GH crosses the BBB. The central nervous system effects of peripheral GH
      can be attributed to permeation of the BBB despite the absence of a specific
      transport system.

PMID- 16099859
TI  - Selective androgen receptor modulator treatment improves muscle strength and body
      composition and prevents bone loss in orchidectomized rats.
AB  - The partial agonist activity of a selective androgen receptor modulator (SARM) in
      the prostate was demonstrated in orchidectomized rats. In the current study, we
      characterized the full agonist activity of S-3-(4-acetylamino-phenoxy)-2-hydroxy
      2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (a structurally
      related SARM referred to in other publications and hereafter as S-4) in skeletal
      muscle, bone, and pituitary of castrated male rats. Twelve weeks after
      castration, animals were treated with S-4 (3 or 10 mg/kg), dihydrotestosterone
      (DHT) (3 mg/kg), or vehicle for 8 wk. S-4 (3 and 10 mg/kg) restored soleus muscle
      mass and strength and levator ani muscle mass to that seen in intact animals.
      Similar changes were also observed in DHT-treated (3 mg/kg) animals. Compared
      with the anabolic effects observed in muscle, DHT (3 mg/kg) stimulated prostate
      and seminal vesicle weights more than 2-fold greater than that observed in intact
      controls, whereas S-4 (3 mg/kg) returned these androgenic organs to only 16 and
      17%, respectively, of the control levels. S-4 (3 and 10 mg/kg) and DHT (3 mg/kg)
      restored castration-induced loss in lean body mass. Furthermore, S-4 treatment
      caused a significantly larger increase in total body bone mineral density than
      DHT. S-4 (3 and 10 mg/kg) also demonstrated agonist activity in the pituitary and
      significantly decreased plasma LH and FSH levels in castrated animals in a dose
      dependent manner. In summary, the strong anabolic effects of S-4 in skeletal
      muscle, bone, and pituitary were achieved with minimal pharmacologic effect in
      the prostate. The tissue-selective pharmacologic activity of SARMs provides
      obvious advantages over steroidal androgen therapy and demonstrates the promising
      therapeutic utility that this new class of drugs may hold.

PMID- 16099860
TI  - Insulin at physiological concentrations selectively activates insulin but not
      insulin-like growth factor I (IGF-I) or insulin/IGF-I hybrid receptors in
      endothelial cells.
AB  - In muscle, physiologic hyperinsulinemia, presumably acting on endothelial cells
      (ECs), dilates arterioles and regulates both total blood flow and capillary
      recruitment, which in turn influences glucose disposal. In cultured ECs, however,
      supraphysiological (e.g. >or=10 nM) insulin concentrations are typically used to
      study insulin receptor (IR) signaling pathways and nitric oxide generation. IGF-I
      receptors (IGF-IRs) are more abundant than IR in ECs, and they also respond to
      high concentrations of insulin. To address whether IR mediates responses to
      physiologic insulin stimuli, we examined the insulin concentration dependence of
      IR and IGF-IR-mediated insulin signaling in bovine aortic ECs (bAECs). We also
      assessed whether insulin/IGF-I hybrid receptors were present in bAECs. Insulin,
      at 100-500 pM, significantly stimulated the phosphorylation of IRbeta, Akt1,
      endothelial isoform of nitric oxide synthase, and ERK 1/2 but not the IGF-IRbeta
      subunit. At concentrations 1-5 nm or greater, insulin dose-dependently enhanced
      the tyrosine phosphorylation of IGF-IRbeta, and this was inhibited by IGF-IR
      neutralizing antibody. In addition, immunoprecipitation of IRbeta pulled down the
      IGF-IRbeta, and the IRbeta immunocytochemically colocalized with IGF-IRbeta,
      suggesting that ECs have insulin/IGF-I hybrid receptors. We conclude that: 1)
      insulin at physiological concentrations selectively activates IR signaling in
      bAECs; 2) bAECs express IGF-IR and insulin/IGF-I hybrid receptors in addition to
      IR; 3) high concentrations of insulin (>or=1-5 nM) activate IGF-IR and hybrid
      receptors as well as IR; and 4) this crossover activation can confound
      interpretation of studies of insulin action in ECs when high insulin
      concentrations are used.

PMID- 16099861
TI  - Perinatal glucocorticoid treatment produces molecular, functional, and
      morphological changes in the anterior pituitary gland of the adult male rat.
AB  - Stress or glucocorticoid (GC) treatment in perinatal life can induce long-term
      changes in the sensitivity of the hypothalamo-pituitary-adrenocortical axis to
      the feedback actions of GCs and, hence, in GC secretion. These changes have been
      ascribed largely to changes in the sensitivity of the limbic system, and possibly
      the hypothalamus, to GCs. Surprisingly, the possibility that early life stress/GC
      treatment may also exert irreversible effects at the pituitary level has scarcely
      been addressed. Accordingly, we have examined the effects of pre- and neonatal
      dexamethasone treatment on the adult male pituitary gland, focusing on the
      following: 1) the integrity of the acute annexin 1 (ANXA1)-dependent inhibitory
      actions of GCs on ACTH secretion, a process requiring ANXA1 release from
      folliculostellate (FS) cells; and 2) the morphology of FS cells and
      corticotrophs. Dexamethasone was given to pregnant (d 16-19) or lactating (d 1-7
      postpartum) rats via the drinking water (1 microg/ml); controls received normal
      drinking water. Pituitary tissue from the offspring was examined ex vivo at d 90.
      Both treatment regimens reduced ANXA1 expression, as assessed by Western blotting
      and quantitative immunogold labeling. In particular, the amount of ANXA1 located
      on the outer surface of the FS cells was reduced. By contrast, IL-6 expression
      was increased, particularly by the prenatal treatment. Pituitary tissue from
      untreated control rats responded to dexamethasone with an increase in cell
      surface ANXA1 and a reduction in forskolin-induced ACTH release. In contrast,
      pituitary tissue from rats treated prenatally or neonatally with dexamethasone
      was unresponsive to the steroid, although, like control tissue, it responded
      readily to ANXA1, which readily inhibited forskolin-driven ACTH release. Prenatal
      dexamethasone treatment reduced the size but not the number of FS cells. It also
      caused a marked reduction in corticotroph number and impaired granule margination
      without affecting other aspects of corticotroph morphology. Similar but less
      marked effects on pituitary cell morphology and number were evident in tissue
      from neonatally treated rats. Our study shows that, when administered by a
      noninvasive process, perinatal GC treatment exerts profound effects on the adult
      pituitary gland, impairing the ANXA1-dependent GC regulation of ACTH release and
      altering the cell profile and morphology.

PMID- 16099862
TI  - Extracellular calcium and parathyroid hormone-related peptide signaling modulate
      the pace of growth plate chondrocyte differentiation.
AB  - An adequate supply of Ca2+ is critical for normal growth plate development.
      Previous studies suggest that changes in extracellular [Ca2+] ([Ca2+]e) modulate
      the function of chondrocytes with high [Ca2+]e promoting cell differentiation. In
      contrast, signal transduction by the PTH/PTHrP type I receptor (PTH1R) slows down
      chondrocyte differentiation. This study addressed whether changes in [Ca2+]e
      modulate the differentiation of mouse growth plate chondrocytes by interacting
      with PTHrP/PTH1Rs. Raising [Ca2+]e from 0.5-3.0 mM dose-dependently promoted the
      development of mouse growth plate chondrocytes as indicated by decreases in
      proteoglycan accumulation and in the expression of early differentiation marker
      genes and by increases in mineral deposition and in the expression of markers of
      terminal differentiation. The effects of high [Ca2+]e on gene expression and
      matrix synthesis were blunted by incubating cells with PTHrP and vice versa. High
      [Ca2+]e also suppressed the expression of PTH1Rs. Chronic stimulation of
      PTHrP/PTH1R signaling by adenoviral expression of constitutively active human
      PTH1Rs (223hPTH1Rs) reduced the effects of high [Ca2+]e on proteoglycan synthesis
      and gene expression. Similar results were seen when we treated cells with
      forskolin or 8-bromo-cAMP. Taken together, these data support the idea that the
      pace of chondrocyte differentiation depends on a balance of interactions between
      PTHrP/PTH1R and extracellular Ca2+ signaling and that high [Ca2+]e promote cell
      differentiation potentially by reducing the availability of PTH1Rs and the level
      of cAMP-dependent signal transduction.

PMID- 16099863
TI  - Up-regulation of c-met protooncogene product expression through hypoxia-inducible
      factor-1alpha is involved in trophoblast invasion under low-oxygen tension.
AB  - During early pregnancy, the invasion of trophoblast cells into the decidua of the
      uterus is one of the essential steps in appropriate placentation. In this period,
      trophoblast cells are exposed to a relatively low-oxygen environment. The c-met
      protooncogene product (Met), which is a high-affinity receptor for hepatocyte
      growth factor, plays an important role in controlling the invasion of many types
      of cells. The present study was designed to investigate the effect of low-oxygen
      tension on Met expression and the invasiveness of trophoblast cells isolated from
      early-stage human placenta and trophoblast-derived BeWo cells and JEG-3 cells. RT
      PCR and immunoblot analyses demonstrated that low-oxygen tension (1% O2)
      stimulated the expression of Met mRNA and protein, respectively. Hepatocyte
      growth factor production in the cells was not affected by oxygen tension.
      Transient transfection of BeWo cells with a hypoxia-inducible factor (HIF)-1alpha
      expression vector to induce exogenous expression of HIF-1alpha significantly
      increased the level of Met mRNA and protein, compared with transfection of a
      control vector. To examine whether this up-regulation of Met was directly induced
      by HIF-1alpha, we performed the chromatin immunoprecipitation assay, which
      revealed that HIF-1alpha binds to the promoter region of the Met gene under low
      oxygen tension. JEG-3 cells cultured under 1% O2 showed a more invasive character
      than those cultured under 20% O2, whereas inhibition of Met expression by small
      interfering RNAs prevented the low-oxygen, tension-induced invasiveness. These
      results suggest that the induction of Met expression by low-oxygen tension may
      play an important role in the physiology of early pregnancy by promoting the
      invasion of trophoblast cells into the decidua of the uterus.

PMID- 16099864
TI  - Estrogens up-regulate the Fas/FasL apoptotic pathway in lactotropes.
AB  - The Fas/FasL system provides the major apoptotic mechanism for many cell types,
      participating in cell turnover in hormone-dependent tissues. In the present
      study, we localized both Fas and FasL in anterior pituitary cells, mainly in
      lactotropes and somatotropes. The percentage of anterior pituitary cells showing
      immunoreactivity for Fas or FasL was higher in cells from rats killed in
      proestrus than in diestrus. Also, the proportion of pituitary cells from
      ovariectomized (OVX) rats expressing Fas or FasL increased in the presence of
      17beta-estradiol (10(-9) M). This steroid increased the percentage of lactotropes
      with immunoreactivity for Fas or FasL and the percentage of somatotropes
      expressing Fas. Activation of Fas by an agonist anti-Fas antibody (Mab-Fas)
      decreased the vi-ability-3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
      bromide (MTT assay)-of anterior pituitary cells from OVX rats cultured in the
      presence of 17beta-estradiol. Also, membrane-bound FasL decreased cell viability
      [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium] assay (MTS assay)-only when anterior pituitary cells from OVX rats
      were incubated with 17beta-estradiol. Moreover, FasL increased the percentage of
      hypodiploid anterior pituitary cells (flow cytometry). Mab-Fas increased the
      percentage of terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick end-labeling (TUNEL)-positive pituitary cells and lactotropes
      from OVX rats only when cells were incubated in the presence of 17beta-estradiol.
      Also, Mab-Fas triggered apoptosis of anterior pituitary cells from rats killed at
      proestrus but not at diestrus. Our results show that 17beta-estradiol up
      regulates the expression of the Fas/FasL system in anterior pituitary cells and
      increases Fas-induced apoptosis in lactotropes, suggesting that Fas-induced
      apoptosis could be involved in the pituitary cell renewal during the estrous
      cycle.

PMID- 16099865
TI  - Characterization of a novel rat epididymal cell line to study epididymal
      function.
AB  - The epididymis is an androgen-dependent organ that allows spermatozoa to become
      fully functional as they pass through this tissue. The specialized functions of
      the epididymis are mediated by interactions between epididymal epithelial cells
      and between epididymal cells and spermatozoa. Although the critical role of the
      epididymis in sperm maturation is well established, the mechanisms regulating
      cell-cell interactions remain poorly understood because of the lack of
      appropriate cell line models. We now report the characterization of a novel rat
      caput epididymal cell line (RCE) that was immortalized by transfecting primary
      cultures of rat epididymal cells with the simian virus 40 large T antigen. At the
      electron microscope level, the cell line was composed of epithelial principal
      cells with characteristics of in vivo cells; principal cells had well-developed
      Golgi apparatus, abundant endoplasmic reticulum cisternae, and few endosomes. RCE
      cells expressed the mRNAs coding for the androgen receptor, estrogen receptor
      alpha, and 4-ene-steroid-5-alpha-reductase types 1 and 2 as well as epididymal
      specific markers Crisp-1 and epididymal retinoic acid binding protein. Epididymal
      retinoic acid binding protein expression was significantly induced with
      dihydrotestosterone, although this effect was not blocked by flutamide,
      suggesting that RCE cells are not androgen responsive. Neighboring cells formed
      tight and gap junctions characteristic of epididymal cells in vivo and expressed
      tight (occludin and claudin-1, -3, and -4) and gap junctional proteins (connexin
      26, -30.3, -32, and -43). The RCE cell line displays many characteristics of
      epithelial principal cells, thus providing a model for studying epididymal cell
      functions.

PMID- 16099866
TI  - Ciprofibrate stimulates the gastrin-producing cell by acting luminally on antral
      PPAR-alpha.
AB  - The lipid-lowering drug ciprofibrate stimulates gastrin-producing cells in the
      rat stomach without lowering gastric acidity. Although suggested to be a luminal
      action on antral peroxisome proliferator-activated receptor-alpha (PPAR-alpha),
      the mechanism is still not fully elucidated. Gastric bypass was surgically
      prepared in male Sprague-Dawley rats. Gastric-bypassed and sham-operated rats
      were either given ciprofibrate (50 mg.kg(-1).day(-1) in methocel) or vehicle
      alone for 7 wk. PPAR-alpha knockout (KO) and wild-type (WT) mice were either
      given ciprofibrate (500 mg.kg(-1).day(-1) in methocel) or vehicle alone for 2 wk.
      The concentration of gastrin in blood was analyzed. Antral G cell density and
      gastrin mRNA abundance were determined by using immunostaining and Northern blot
      analysis. Ciprofibrate did not raise plasma gastrin or G cell density in gastric
      bypassed rats, although the gastrin mRNA level was slightly increased. In
      contrast, ciprofibrate induced hypergastrinemia, a 50% increase in G cell
      density, and a threefold increase in gastrin mRNA in sham-operated rats. In PPAR
      alpha KO mice, ciprofibrate did not raise G cell density or the gastrin mRNA
      level. The serum gastrin level was reduced by ciprofibrate. In WT mice,
      ciprofibrate induced hypergastrinemia, a doubling of G cell density, and a
      threefold increase in gastrin mRNA. Comparing animals dosed with vehicle only,
      PPAR-alpha KO mice had higher serum gastrin concentration than WT mice. We
      conclude that the main effects of ciprofibrate on G cells are mediated from the
      antrum lumen, and the mechanism is dependent on PPAR-alpha. The results indicate
      that PPAR-alpha may have a role in the physiological regulation of gastrin
      release.

PMID- 16099867
TI  - Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell
      levels of cGMP in isolated human gastric glands.
AB  - We have previously identified cells containing the enzyme nitric oxide (NO)
      synthase (NOS) in the human gastric mucosa. Moreover, we have demonstrated that
      endogenous and exogenous NO has been shown to decrease histamine-stimulated acid
      secretion in isolated human gastric glands. The present investigation aimed to
      further determine whether this action of NO was mediated by the activation of
      guanylyl cyclase (GC) and subsequent production of cGMP. Isolated gastric glands
      were obtained after enzymatic digestion of biopsies taken from the oxyntic mucosa
      of healthy volunteers. Acid secretion was assessed by measuring
      [(14)C]aminopyrine accumulation, and the concentration of cGMP was determined by
      radioimmunoassay. In addition, immunohistochemistry was used to examine the
      localization of cGMP in mucosal preparations after stimulation with the NO donor
      S-nitroso-N-acetylpenicillamine (SNAP). SNAP (0.1 mM) was shown to decrease acid
      secretion stimulated by histamine (50 microM); this effect was accompanied by an
      increase in cGMP production, which was histologically localized to parietal
      cells. The membrane-permeable cGMP analog dibuturyl-cGMP (db-cGMP; 0.1-1 mM) dose
      dependently inhibited acid secretion. Additionally, the effect of SNAP was
      prevented by preincubating the glands with the GC inhibitor 4H-8-bromo-1,2,4
      oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 microM). We therefore suggest that
      NO in the human gastric mucosa is of physiological importance in regulating acid
      secretion. Furthermore, the results show that NO-induced inhibition of gastric
      acid secretion is a cGMP-dependent mechanism in the parietal cell involving the
      activation of GC.

PMID- 16099868
TI  - T cell-induced inflammation of the small and large intestine in immunodeficient
      mice.
AB  - It is well known that transfer of CD4+CD45RBhigh (naive) T cells into syngeneic
      lymphocyte-deficient mice induces chronic colitis. However, no studies have
      reported the presence of small bowel inflammation in this T cell-dependent model.
      Therefore, the objective of this study was to evaluate and compare small and
      large bowel inflammation induced by transfer of naive T cells into two different
      immunodeficient recipient mice. T and B cell-deficient recombinase activating
      gene 1-deficient [RAG knockout (KO)] and T cell-deficient T cell receptor-beta x
      T cell receptor-delta double-deficient (TCR KO) mice were reconstituted with wild
      type naive T cells and observed for signs of disease. We found that reconstituted
      RAG KO mice developed moderate to severe colitis and inflammation of the entire
      small intestine at 6-8 wk after T cell transfer. Adoptive transfer of naive T
      cells into TCR KO mice induced a milder form of chronic colitis and small bowel
      inflammation that was confined primarily to the duodenum at 10-12 wk after T cell
      transfer. T helper cell 1 and macrophage-derived proinflammatory cytokine mRNA
      levels correlated well with the localization and severity of the chronic large
      and small bowel inflammation. In addition, we observed comparable homing and
      expansion of donor lymphocytes in the gut and secondary lymphoid tissues of both
      recipients. Taken together, our data demonstrate that transfer of naive T cells
      into immunodeficient recipient mice induces both chronic small and large bowel
      inflammation and that the presence of B cells in the TCR KO recipients may play a
      role in regulating chronic intestinal inflammation.

PMID- 16099869
TI  - Spatiotemporal electrical and motility mapping of distension-induced propagating
      oscillations in the murine small intestine.
AB  - Since the development of knockout animals, the mouse has become an important
      model to study gastrointestinal motility. However, little information is
      available on the electrical and contractile activities induced by distension in
      the murine small intestine. Spatiotemporal electrical mapping and mechanical
      recordings were made from isolated intestinal segments from different regions of
      the murine small intestine during distension. The electrical activity was
      recorded with 16 extracellular electrodes while motility was assessed
      simultaneously by tracking the border movements with a digital camera. Distension
      induced propagating oscillatory contractions in isolated intestinal segments.
      These propagating contractions were dictated by the underlying propagating slow
      wave with superimposed spikes. The frequencies, velocities, and direction of the
      propagating oscillations strongly correlated with the frequencies (r = 0.86),
      velocities (r = 0.84), and direction (r = 1) of the electrical slow waves.
      N(omega)-nitro-L-arginine methyl ester decreased the maximal diameter of the
      segment and reduced the peak contraction amplitude of the propagating oscillatory
      contractions, whereas atropine and verapamil blocked the propagating
      oscillations. Tetrodotoxin had little effect on the maximal diameter and peak
      contraction amplitude. In conclusion, distension in the murine small intestine
      does not initiate peristaltic reflexes but induces a propagating oscillatory
      motor pattern that is determined by propagating slow waves with superimposed
      spikes. These spikes are cholinergic and calcium dependent.

PMID- 16099870
TI  - Phosphatidylcholine transfer protein regulates size and hepatic uptake of high
      density lipoproteins.
AB  - Phosphatidylcholine transfer protein (PC-TP) is a steroidogenic acute regulatory
      related transfer domain protein that is enriched in liver cytosol and binds
      phosphatidylcholines with high specificity. In tissue culture systems, PC-TP
      promotes ATP-binding cassette protein A1-mediated efflux of cholesterol and
      phosphatidylcholine molecules as nascent pre-beta-high-density lipoprotein (HDL)
      particles. Here, we explored a role for PC-TP in HDL metabolism in vivo utilizing
      8-wk-old male Pctp(-/-) and wild-type littermate C57BL/6J mice that were fed for
      7 days with either chow or a high-fat/high-cholesterol diet. In chow-fed mice,
      neither plasma cholesterol concentrations nor the concentrations and compositions
      of plasma phospholipids were influenced by PC-TP expression. However, in Pctp(-/
      ) mice, there was an accumulation of small alpha-migrating HDL particles. This
      occurred without changes in hepatic expression of ATP-binding cassette protein A1
      or in proteins that regulate the intravascular metabolism and clearance of HDL
      particles. In Pctp(-/-) mice fed the high-fat/high-cholesterol diet, HDL particle
      sizes were normalized, whereas plasma cholesterol and phospholipid concentrations
      were increased compared with wild-type mice. In the absence of upregulation of
      hepatic ATP-binding cassette protein A1, reduced HDL uptake from plasma into
      livers of Pctp(-/-) mice contributed to higher plasma lipid concentrations. These
      data indicate that PC-TP is not essential for the enrichment of HDL with
      phosphatidylcholines but that it does modulate particle size and rates of hepatic
      clearance.

PMID- 16099871
TI  - Na-glucose and Na-neutral amino acid cotransport are uniquely regulated by
      constitutive nitric oxide in rabbit small intestinal villus cells.
AB  - Na-nutrient cotransport processes are not only important for the assimilation of
      essential nutrients but also for the absorption of Na in the mammalian small
      intestine. The effect of constitutive nitric oxide (cNO) on Na-glucose (SGLT-1)
      and Na-amino acid cotransport (NAcT) in the mammalian small intestine is unknown.
      Inhibition of cNO synthase with N(G)-nitro-l-arginine methyl ester (L-NAME)
      resulted in the inhibition of Na-stimulated (3)H-O-methyl-D-glucose uptake in
      villus cells. However, Na-stimulated alanine uptake was not affected in these
      cells. The L-NAME-induced reduction in SGLT-1 in villus cells was not secondary
      to an alteration in basolateral membrane Na-K-ATPase activity, which provides the
      favorable Na gradient for this cotransport process. In fact, SGLT-1 was inhibited
      in villus cell brush-border membrane (BBM) vesicles prepared from animals treated
      with L-NAME. Kinetic studies demonstrated that the mechanism of inhibition of
      SGLT-1 was secondary to a decrease in the affinity for glucose without a change
      in the maximal rate of uptake of glucose. Northern blot studies demonstrated no
      change in the mRNA levels of SGLT-1. Western blot studies demonstrated no
      significant change in the immunoreactive protein levels of SGLT-1 in ileal villus
      cell BBM from L-NAME-treated rabbits. These studies indicate that inhibition of
      cNO production inhibits SGLT-1 but not NAcT in the rabbit small intestine.
      Therefore, whereas cNO promotes Na-glucose cotransport, it does not affect NAcT
      in the mammalian small intestine.

PMID- 16099872
TI  - Topical antisense oligonucleotide therapy against LIX, an enterocyte-expressed
      CXC chemokine, reduces murine colitis.
AB  - Epithelial neutrophil-activating peptide-78 (ENA-78), a member of the CXC
      chemokine subfamily, is induced by inflammatory cytokines in human colonic
      enterocyte cell lines and increased in the colon of patients with inflammatory
      bowel disease (IBD). Lipopolysaccharide-induced CXC-chemokine (LIX) was recently
      identified as the murine homolog of ENA-78. Here we show that, similar to ENA-78,
      inflammatory cytokine stimulation of a murine colonic epithelial cell line, MODE
      K, results in increased LIX expression. Consistent with the expression pattern of
      ENA-78 in IBD, LIX expression is significantly increased in mice with colitis
      induced by the ingestion of dextran sodium sulfate (DSS). Treating mice with
      antisense oligonucleotides to LIX via rectal enema delivery before DSS treatment
      results in colonic enterocyte uptake and a significant reduction in neutrophil
      infiltration and severity of colitis. These findings indicate that LIX plays an
      integral role in the pathogenesis of DSS-induced colitis. Similarly, enterocyte
      derived CXC chemokines may play a key role in regulating neutrophil recruitment
      and intestinal injury in IBD. The intracolonic administration of ENA-78 antisense
      oligonucleotides may be effective in treating distal ulcerative colitis in
      humans.

PMID- 16099873
TI  - Constitutive NF-kappaB and NFAT activation in aggressive B-cell lymphomas
      synergistically activates the CD154 gene and maintains lymphoma cell survival.
AB  - Abnormalities in B-lymphocyte CD40 ligand (CD154) expression have been described
      for a number of immunologic diseases, including B-cell lymphomas. Although
      functional analysis of the CD154 gene and protein has been extensive, little is
      known about the mechanisms controlling CD154 expression in activated T cells, and
      even less is known for normal and malignant B cells. In this study we describe
      the transcriptional mechanism controlling CD154 expression in large B-cell
      lymphoma (LBCL). We show that the nuclear factor of activated T cells (NFAT)
      transcription factor is also constitutively activated in LBCL. We demonstrate
      that the constitutively active NFATc1 and c-rel members of the NFAT and nuclear
      factor-kappaB (NF-kappaB) families of transcription factors, respectively,
      directly interact with each other, bind to the CD154 promoter, and
      synergistically activate CD154 gene transcription. Down-regulation of NFATc1 or c
      rel with small interfering RNA (siRNA) or chemical inhibitors inhibits CD154 gene
      transcription and lymphoma cell growth. These findings suggest that targeting NF
      kappaB and NFAT, by inhibiting the expression of these transcription factors, or
      interdicting their interaction may provide a therapeutic rationale for patients
      with non-Hodgkin lymphoma of B-cell origin, and possibly other disorders that
      display dysregulated CD154 expression.

PMID- 16099874
TI  - Secretion of IFN-gamma and not IL-2 by anergic human T cells correlates with
      assembly of an immature immune synapse.
AB  - We report differences in the supramolecular organization of the immunologic
      synapse (IS) formed by resting and anergic human T cells with agonist peptide
      loaded antigen-presenting cells (APCs). T cells reactive to influenza A
      hemagglutinin peptide or Fel d 1 peptide 4 were rendered both anergic and
      regulatory by incubation with high doses of agonist peptide in the absence of
      APCs. At the IS between resting T cells and peptide-loaded APCs, both CD3epsilon
      and CD3zeta initially accumulate within a ring or arc before redistributing
      within 30 minutes to single or multiple foci more central to the contact. In
      contrast, at synapses formed by anergized T cells, CD3epsilon and CD3zeta
      remained organized within an arc or ring and failed to redistribute centrally.
      However, intercellular communication between anergic human T cells and agonist
      peptide-loaded APCs was not a null event, since it triggered secretion of T-cell
      interferon gamma (IFN-gamma) but not, for example, interleukin 2 (IL-2). Thus,
      distinct organizations of CD3 at the T-cell IS correlate with different cytokine
      profiles; the mature IS formed by resting T cells correlates with their
      production of both IFN-gamma and IL-2, whereas the immature IS formed by anergic
      T cells seems able to facilitate IFN-gamma but not IL-2 production.

PMID- 16099875
TI  - A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells.
AB  - Proinflammatory T helper 1 (Th1) cells express high levels of carbohydrate
      ligands for the endothelial selectins, but the molecular basis for this phenotype
      is incompletely understood. We document here a significant role in selectin
      ligand formation for the recently described Th1 transcription factor T-bet. Th1
      cells generated from T-bet-/- mice showed significantly lower levels of ligands
      for both E-selectin and P-selectin, compared with wild-type (WT) Th1 cells.
      Enforced expression of T-bet in WT Th0 cells only modestly up-regulated P
      selectin ligands and had no effect on E-selectin ligands. To define a mechanism
      for the defects observed in T-bet-/- mice, we examined expression of
      glycosyltransferases involved in selectin ligand biosynthesis. T-bet-/- Th1 cells
      expressed significantly lower levels of core 2 beta1,6 N
      acetylglucosaminyltransferase I (C2GlcNAcT-I), but no differences in levels of
      alpha 2,3-sialyltransferase IV (ST3Gal-IV). Further, we show that T-bet is
      responsible for the signal transducer and activator of transcription 4 (Stat4)
      independent increase in Th1 cells of fucosyltransferase VII (FucT-VII). We also
      identify ST3Gal-VI, which is thought to play an important role in E- and P
      selectin ligand formation, as an interleukin 12 (IL-12)-regulated, T-bet
      dependent gene. These data show that T-bet controls selectin ligand formation in
      Th1 cells via control of expression of multiple key enzymes in response to IL-12
      signaling and establishes an independent transcriptional pathway for control of
      Th1 cell traffic.

PMID- 16099876
TI  - p21-activated kinase (Pak) regulates NADPH oxidase activation in human
      neutrophils.
AB  - The phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays
      an instrumental role in host defense and contributes to microbicial killing by
      releasing highly reactive oxygen species. This multicomponent enzyme is composed
      of membrane and cytosolic components that assemble in the plasma membrane or
      phagolysosome. While the guanosine S'-triphosphatase (GTPase) Rac2 has been shown
      to be a critical regulator of NADPH oxidase activity and assembly, the role of
      its effector, p21-activated kinase (Pak), in oxidase function has not been well
      defined. Using HIV-1 Tat-mediated protein transduction of Pak inhibitory domain,
      we show here that Pak activity is indeed required for efficient superoxide
      generation in intact neutrophils. Furthermore, we show that Pak translocates to
      the plasma membrane upon N-formyl-methionyl-leucyl-phenylalanine (fMLF)
      stimulation and colocalizes with translocated p47(phox) and with p22phox, a
      subunit of flavocytochrome b558. Although activated Pak phosphorylated several
      essential serine residues in the C-terminus of p47phox, direct binding to p47phox
      was not observed. In contrast, active Pak bound directly to p22phox, suggesting
      flavocytochrome b was the oxidase-associated membrane target of this kinase and
      this association may facilitate further phosphorylation of p47phox in the
      assembling NADPH oxidase complex.

PMID- 16099877
TI  - Long-term outcome of individuals with pure red cell aplasia and
      antierythropoietin antibodies in patients treated with recombinant epoetin: a
      follow-up report from the Research on Adverse Drug Events and Reports (RADAR)
      Project.
AB  - Since its introduction in 1988, recombinant human erythropoietin (epoetin) has
      been standard treatment for patients with anemia due to chronic kidney disease.
      From 1998 to 2004, nearly 200 epoetin-treated persons with chronic kidney disease
      developed antibodies to epoetin, resulting in pure red cell aplasia (PRCA). The
      majority of these patients received Eprex, an epoetin alfa product marketed
      exclusively outside the United States. Herein, we report on the long-term outcome
      of these individuals. For 170 chronic kidney disease patients who developed
      epoetin-associated PRCA and had 3 months or more follow-up information available,
      case reports from the Food and Drug Administration and epoetin manufacturers were
      reviewed for information on clinical characteristics of the patients,
      immunosuppressive treatments, epoetin responsiveness, and hematologic recovery.
      Overall, 64% of the PRCA patients received immunosuppressive therapy, including
      19 who also underwent a renal transplantation. Thirty-seven percent experienced a
      hematologic recovery, with higher hematologic recovery rates among PRCA patients
      who received immunosuppressive therapy (57% vs 2%, P < .001). Among 34 patients
      who received epoetin after the onset of PRCA, 56% regained epoetin
      responsiveness. The highest rates of epoetin responsiveness were observed among
      persons whose antierythropoietin antibodies were undetectable when epoetin was
      administered (89%). Among chronic kidney disease patients with epoetin-associated
      PRCA, epoetin discontinuation and immunosuppressive therapy or renal
      transplantation is necessary for hematologic recovery. Reinitiation of epoetin
      therapy among individuals could be considered if antierythropoietin antibodies
      are undetectable.

PMID- 16099878
TI  - Molecular identification of PAL-E, a widely used endothelial-cell marker.
AB  - The pathologische anatomie Leiden-endothelium (PAL-E) antibody has been used for
      almost 20 years as a specific marker for vascular endothelial cells. Due to the
      fact that this antibody works only in very limited applications, the molecular
      identity of PAL-E has remained unknown. In this work, we demonstrate by double
      stainings, cross-immunoprecipitations, and transfectants that the PAL-E antigen
      is identical with a protein designated PV-1 (plasmalemmal vesicle 1) or FELS
      (fenestrated endothelial-linked structure protein) and is not vimentin, as
      reported earlier. As the expression of this molecule is by no means restricted to
      fenestrated endothelium, we suggest the use of the name PLVAP for this protein.
      Molecular identification of PLVAP should help in the production of new tools for
      the identification of vascular as opposed to lymphatic endothelium and to
      elucidate the function of this protein.

PMID- 16099879
TI  - Analysis of thrombocyte development in CD41-GFP transgenic zebrafish.
AB  - Thrombocytes are the nucleated equivalent of platelets in nonmammalian
      vertebrates such as the zebrafish, Danio rerio. We have cloned zebrafish CD41
      cDNA (alpha(IIb), glycoprotein IIb [GPIIb]) and its promoter and have generated
      transgenic zebrafish lines with green fluorescent protein (GFP)-tagged
      thrombocytes. CD41 mRNA transcripts appeared 42 hours after fertilization (hpf)
      by reverse-transcriptase-polymerase chain reaction (RT-PCR) and at 48 hpf in
      circulating hematopoietic cells. Flow sorting of thrombocytes from the
      mesonephros of adult CD41-GFP zebrafish showed a GFP(high) subset, which had the
      morphologic appearance of mature thrombocytes, and a GFP(low) subset with an
      immature appearance, suggesting that they may be thrombocyte precursors. Confocal
      laser microscopy of embryos 40 and 48 hpf also showed a nonmobile population of
      GFP+ cells in a discrete area between the dorsal aorta and caudal vein.
      Production of circulating thrombocytes was inhibited by the injection of
      antisense morpholinos for the stem-cell transcription factor scl and c-mpl, the
      receptor for thrombopoietin. The nonmobile pool of GFP+ cells was abolished by
      scl knockdown and partially inhibited by c-mpl knockdown. These studies have
      shown that it is possible to identify thrombocytes, thrombocyte precursors, and,
      possibly, early hematopoietic stem cells in zebrafish embryos and track their
      proliferation and maturation.

PMID- 16099880
TI  - Donor origin of multipotent adult progenitor cells in radiation chimeras.
AB  - Multipotent adult progenitor cells (MAPCs) are bone marrow-derived stem cells
      that have extensive in vitro expansion capacity and can differentiate in vivo and
      in vitro into tissue cells of all 3 germinal layers: ectoderm, mesoderm, and
      endoderm. The origin of MAPCs within bone marrow is unknown. MAPCs are believed
      to be derived from the bone marrow stroma compartment as they are isolated within
      the adherent cell component. Numerous studies of bone marrow chimeras in the
      human and the mouse point to a host origin of bone marrow stromal cells.
      Mesenchymal stem cells (MSCs), which coexist with stromal cells, have also been
      proven to be of host origin after allogeneic bone marrow transplantation in
      numerous studies. We report here that following syngeneic bone marrow transplants
      into lethally irradiated C57BL6 mice, MAPCs are of donor origin.

PMID- 16099881
TI  - AIDS-related lymphoproliferative disease.
AB  - Not long after the recognition of HIV as the causative agent of AIDS, it was
      evident that individuals infected with HIV developed lymphoma at a greater rate
      than the population at large. Approximately two thirds of AIDS-related lymphoma
      (ARL) cases are categorized as diffuse large B-cell type, with Burkitt lymphomas
      comprising 25% and other histologies a much smaller proportion. Typically, these
      individuals have presented with advanced extranodal disease and CD4+ lymphocyte
      counts of less than 200/mm3. Recent clinical trials have demonstrated a better
      outcome with chemotherapy for ARL since the introduction of combination
      antiretroviral treatment, termed highly active antiretroviral therapy (HAART).
      For patients with relapses, solid evidence points to the safety and utility of
      hematopoietic-cell transplantation as a salvage modality. Coinfection with other
      viruses such as Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus have
      led to the genesis of previously rare or unrecognized lymphoma subtypes such as
      plasmablastic and primary effusion lymphomas. The immunosuppressive impact of
      treatment for patients with ARL receiving chemotherapy with HAART appears
      transient and opportunistic infections have become less problematic than prior to
      HAART. Significant progress has been made in the understanding and management of
      ARL but outcomes still remain inferior compared to those achieved in HIV-
      individuals.

PMID- 16099882
TI  - How I treat venous thrombosis in children.

PMID- 16099883
TI  - Endogenous NGF regulates CGRP expression in human monocytes, and affects HLA-DR
      and CD86 expression and IL-10 production.
AB  - Our recent results on autocrine nerve growth factor (NGF) synthesis in B
      lymphocytes, which directly regulates the expression and release of calcitonin
      gene-related peptide (CGRP), a neuropeptide known to down-regulate immune
      response, led us to propose an anti-inflammatory action of NGF. In the present
      work, we investigated whether the endogenous synthesis of NGF can regulate the
      expression of CGRP in other antigen-presenting cells, such as monocytes, and
      whether this may have a functional effect. Our data indicate that human monocytes
      synthesize basal levels of NGF and CGRP and that, following lipopolysaccharide
      (LPS) stimulation, NGF and CGRP expression are both up-regulated. When endogenous
      NGF is neutralized, the up-regulation of CGRP expression induced by LPS is
      inhibited. The expression of membrane molecules involved in T-cell activation
      such as human leukocyte antigen-DR (HLA-DR) and CD86 is affected by endogenous
      NGF, and similar effects were obtained using a CGRP(1) receptor antagonist. In
      addition, NGF deprivation in LPS-treated monocytes significantly decreases
      interleukin 10 (IL-10) synthesis. Our findings indicate that endogenous NGF
      synthesis has a functional role and may represent a physiologic mechanism to down
      regulate major histocompatibility complex (MHC) class II and CD86 expression and
      alter the development of immune responses.

PMID- 16099884
TI  - Up-regulated expression in nonhematopoietic tissues of the BCL2A1-derived minor
      histocompatibility antigens in response to inflammatory cytokines: relevance for
      allogeneic immunotherapy of leukemia.
AB  - T cells directed against hematopoietic-restricted minor histocompatibility
      antigens (mHags) may mediate graft-versus-leukemia (GVL) reactivity without graft
      versus-host disease (GVHD). Recently, the HLA-A24-restricted mHag ACC-1 and the
      HLA-B44-restricted mHag ACC-2 encoded by separate polymorphisms within the BCL2A1
      gene were characterized. Hematopoietic-restricted expression was suggested for
      these mHags. We demonstrate BCL2-related protein A1 (BCL2A1) mRNA expression in
      mesenchymal stromal cells (MSCs) that was up-regulated by the inflammatory
      cytokines tumor necrosis factor alpha (TNF-alpha) and/or interferon gamma (IFN
      gamma). Analysis of cytotoxicity and IFN-gamma production illustrated that ACC-2
      specific T cells did not recognize untreated MSCs or IFN-gamma-treated MSCs but
      showed specific recognition and killing of MSCs treated with TNF-alpha plus IFN
      gamma. We hypothesize that under steady-state circumstances BCL2A1-specific T
      cells may exhibit relative specificity for hematopoietic tissue, but reactivity
      against nonhematopoietic cells may occur when inflammatory infiltrates are
      present. Thus, the role of BCL2A1-specific T cells in differential induction of
      GVL reactivity and GVHD may depend on the presence of inflammatory responses that
      may occur during GVHD.

PMID- 16099885
TI  - Mechanism and effect of thrombospondin-4 polymorphisms on neutrophil function.
AB  - High-throughput genomic technology identified an association between a single
      nucleotide polymorphism (SNP), a proline (P387) rather than the predominant
      alanine (A387) at position 387 in thrombospondin-4 (TSP-4) and premature
      myocardial infarction. The inflammatory hypothesis of atherosclerosis invokes a
      prominent role of leukocytes and cytokines in pathogenesis. As the expression of
      TSP-4 by vascular cells permits its exposure to circulating leukocytes, the
      interactions of human neutrophils (polymorphonuclear leukocytes [PMNs]) with both
      TSP-4 variants were investigated. Phorbol 12-myristate 13-acetate (PMA)
      stimulated PMNs adhered and migrated well and equally on the TSP-4 variants.
      Integrin alpha(M)beta2 was identified as the TSP-4 receptor mediating these
      responses, and the 3 epidermal growth factor (EGF)-like domains of TSP-4
      harboring the SNPs interacted with the alpha(M)I-domain. Despite the similarity
      in these responses, the P387 variant induced more robust tyrosine phosphorylation
      of the stress-related mitogen-activated protein kinases (MAPKs): p38MAPK and c
      Jun NH2-terminal kinase (JNK), as well as signal transducer and activator of
      transcription-1 (STAT1) and heat shock protein 27 (HSP27) than the A387 variant.
      Additionally, cells adherent to P387 TSP-4 variant released 4-fold more H2O2 and
      secreted 2-fold more interleukin 8 (IL-8) as compared with the A387. H2O2 release
      and p38MAPK activation were totally inhibited by blockade of alpha(M)beta2. Thus,
      alpha(M)beta2 plays a central role in proinflammatory activities of TSP-4 (P387)
      and may contribute to the prothrombotic phenotype associated with this variant.

PMID- 16099886
TI  - Oxidized beta2-glycoprotein I induces human dendritic cell maturation and
      promotes a T helper type 1 response.
AB  - The human plasma protein beta2-glycoprotein I (beta2-GPI) is the most common
      target for antiphospholipid antibodies associated with thrombotic events in
      chronic disorders related to endothelial cell dysfunction. Crucial information is
      needed to clarify why this self-abundant protein is targeted by autoimmune
      responses. In this study, we investigated whether oxidative modification of beta2
      GPI, either spontaneous in culture wells or induced by treatment with H2O2,
      renders this self-protein able to activate immature monocyte-derived dendritic
      cells (DCs) from healthy human donors. Oxidized beta2-GPI caused DCs to mature so
      that CD83 appeared and CD80, CD86, human leukocyte antigen-D region related (HLA
      DR), and CD40 increased. The interaction between oxidized beta2-GPI and DCs
      specifically stimulated these cells to secrete interleukin 12 (IL-12), IL-1beta,
      IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and IL-10. Oxidized beta2
      GPI-stimulated DCs had increased allostimulatory ability and primed naive T
      lymphocytes, thus inducing T helper 1 (Th1) polarization. The interaction between
      oxidized beta2-GPI and DCs involved interleukin-1 receptor associated kinase
      (IRAK) phosphorylation and nuclear factor kappaB (NFkappaB) activation.
      Pretreatment of beta2-GPI with the antioxidant alpha-tocopherol prevented DC
      maturation. These findings show that human oxidized beta2-GPI, probably by
      interacting with a member of the Toll-like receptor (TLR) family, causes DCs to
      mature. Because this key beta2-GPI function requires oxidative modification, in
      several chronic disorders related to endothelial cell dysfunction oxidative
      stress might trigger the "autoimmune spiral."

PMID- 16099887
TI  - Risk factors and kinetics of thrombocytopenia associated with bortezomib for
      relapsed, refractory multiple myeloma.
AB  - Bortezomib, a proteasome inhibitor with efficacy in multiple myeloma, is
      associated with thrombocytopenia, the cause and kinetics of which are different
      from those of standard cytotoxic agents. We assessed the frequency, kinetics, and
      mechanism of thrombocytopenia following treatment with bortezomib 1.3 mg/m2 in
      228 patients with relapsed and/or refractory myeloma in 2 phase 2 trials. The
      mean platelet count decreased by approximately 60% during treatment but recovered
      rapidly between treatments in a cyclic fashion. Among responders, the
      pretreatment platelet count increased significantly during subsequent cycles of
      therapy. The mean percent reduction in platelets was independent of baseline
      platelet count, M-protein concentration, and marrow plasmacytosis. Plasma
      thrombopoietin levels inversely correlated with platelet count. Murine studies
      demonstrated a reduction in peripheral platelet count following a single
      bortezomib dose without negative effects on megakaryocytic cellularity, ploidy,
      or morphology. These data suggest that bortezomib-induced thrombocytopenia is due
      to a reversible effect on megakaryocytic function rather than a direct cytotoxic
      effect on megakaryocytes or their progenitors. The exact mechanism underlying
      bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be
      related to marrow injury or decreased thrombopoietin production.

PMID- 16099888
TI  - Modulation of endothelial and smooth muscle function by bed rest and
      hypoenergetic, low-fat nutrition.
AB  - Prolonged microgravity alters the regulation of the peripheral vasculature. The
      influence of reduced food intake, as often observed in astronauts, on vascular
      function is unclear. In a randomized, four-phase, crossover study, the effect of
      simulated microgravity (13 days of bed rest), energetic restriction (-25%, fat
      reduced), and their combination on endothelium-dependent and -independent
      vasodilation was compared with ambulatory control conditions. Using venous
      occlusion plethysmography, cumulative intra-arterial dose-response curves to
      endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside)
      vasodilators were constructed in 10 healthy male volunteers before and on day 13
      of each of the four intervention periods. Bed rest combined with normoenergetic
      nutrition impaired the dose-response to acetylcholine (ANOVA, P = 0.004) but not
      to sodium nitroprusside, whereas hypoenergetic diet under ambulatory conditions
      improved responses to acetylcholine (P = 0.044) and sodium nitroprusside (P <
      0.001). When bed rest was combined with hypoenergetic diet, acetylcholine
      responses did not change. Similarly, under control conditions, no change was
      observed. Individual changes in the total cholesterol-to-HDL ratio were
      correlated with changes in endothelial and vascular smooth muscle relaxation. In
      conclusion, short-term bed rest impairs endothelium-dependent arterial relaxation
      in humans. A hypoenergetic, low-fat diet modulates serum lipids, improves
      endothelium-dependent and -independent relaxation, and may antagonize the
      unfavorable effects of simulated microgravity on endothelial function.

PMID- 16099889
TI  - Insulin-independent pathways mediating glucose uptake in hindlimb-suspended
      skeletal muscle.
AB  - Insulin resistance accompanies atrophy in slow-twitch skeletal muscles such as
      the soleus. Using a rat hindlimb suspension model of atrophy, we have previously
      shown that an upregulation of JNK occurs in atrophic muscles and correlates with
      the degradation of insulin receptor substrate-1 (IRS-1) (Hilder TL, Tou JC,
      Grindeland RF, Wade CE, and Graves LM. FEBS Lett 553: 63-67, 2003), suggesting
      that insulin-dependent glucose uptake may be impaired. However, during atrophy,
      these muscles preferentially use carbohydrates as a fuel source. To investigate
      this apparent dichotomy, we examined insulin-independent pathways involved in
      glucose uptake following a 2- to 13-wk hindlimb suspension regimen. JNK activity
      was elevated throughout the time course, and IRS-1 was degraded as early as 2 wk.
      AMP-activated protein kinase (AMPK) activity was significantly higher in atrophic
      soleus muscle, as were the activities of the ERK1/2 and p38 MAPKs. As a
      comparison, we examined the kinase activity in solei of rats exposed to
      hypergravity conditions (2 G). IRS-1 phosphorylation, protein, and AMPK activity
      were not affected by 2 G, demonstrating that these changes were only observed in
      soleus muscle from hindlimb-suspended animals. To further examine the effect of
      AMPK activation on glucose uptake, C2C12 myotubes were treated with the AMPK
      activator metformin and then challenged with the JNK activator anisomycin. While
      anisomycin reduced insulin-stimulated glucose uptake to control levels, metformin
      significantly increased glucose uptake in the presence of anisomycin and was
      independent of insulin. Taken together, these results suggest that AMPK may be an
      important mediator of insulin-independent glucose uptake in soleus during
      skeletal muscle atrophy.

PMID- 16099890
TI  - Transdiaphragmatic transport of tracer albumin from peritoneal to pleural liquid
      measured in rats.
AB  - In conscious Wistar-Kyoto rats, we studied the uptake of radioactive tracer
      (125)I-albumin into the pleural space and circulation after intraperitoneal (IP)
      injections with 1 or 5 ml of Ringer solution (3 g/dl albumin). Postmortem, we
      sampled pleural liquid, peritoneal liquid, and blood plasma 2-48 h after IP
      injection and measured their radioactivity and protein concentration. Tracer
      concentration was greater in pleural liquid than in plasma approximately 3 h
      after injection with both IP injection volumes. This behavior indicated transport
      of tracer through the diaphragm into the pleural space. A dynamic analysis of the
      tracer uptake with 5-ml IP injections showed that at least 50% of the total
      pleural flow was via the diaphragm. A similar estimate was derived from an
      analysis of total protein concentrations. Both estimates were based on restricted
      pleural capillary filtration and unrestricted transdiaphragmatic transport. The 5
      ml IP injections did not change plasma protein concentration but increased
      pleural and peritoneal protein concentrations from control values by 22 and 30%,
      respectively. These changes were consistent with a small (approximately 8%)
      increase in capillary filtration and a small (approximately 20%) reduction in
      transdiaphragmatic flow from control values, consistent with the small (3%)
      decrease in hydration measured in diaphragm muscle. Thus the pleural uptake of
      tracer via the diaphragm with the IP injections occurred by the near-normal
      transport of liquid and protein.

PMID- 16099891
TI  - Motor unit behavior during clonus.
AB  - Medial gastrocnemius surface electromyographic activity and intramuscular
      electromyographic activity were recorded from six individuals with chronic
      cervical spinal cord injury to document the recruitment order of motor units
      during clonus. Four subjects induced clonus that lasted up to 30 s while two
      subjects induced clonus that they actively stopped after 1 min. Mean clonus
      frequency in different subjects ranged from 4.7 to 7.0 Hz. Most of the 166 motor
      units recorded during clonus (98%) fired once during each contraction but at
      slightly different times during each cycle. Other motor units fired during some
      clonus cycles (1%) or in bursts (1%). When 59 pairs of units were monitored over
      consecutive clonus cycles (n = 5-89 cycles), only 8 pairs of units altered their
      recruitment order in some cycles. Recruitment reversals only occurred in units
      that fired close together in the clonus cycle. These data demonstrate that
      orderly motor unit recruitment occurs during involuntary contractions of muscles
      paralyzed chronically by cervical spinal cord injury, providing further support
      for the importance of spinal mechanisms in the control of human motor unit
      behavior.

PMID- 16099892
TI  - Cerebral blood flow velocity during mental activation: interpretation with
      different models of the passive pressure-velocity relationship.
AB  - The passive relationship between arterial blood pressure (ABP) and cerebral blood
      flow velocity (CBFV) has been expressed by a single parameter [cerebrovascular
      resistance (CVR)] or, alternatively, by a two-parameter model, comprising a
      resistance element [resistance-area product (RAP)] and a critical closing
      pressure (CrCP). We tested the hypothesis that the RAP+CrCP model can provide a
      more consistent interpretation to CBFV responses induced by mental activation
      tasks than the CVR model. Continuous recordings of CBFV [bilateral, middle
      cerebral artery (MCA)], ABP, ECG, and end-tidal CO(2) (EtCO(2)) were performed in
      13 right-handed healthy subjects (aged 21-43 yr), in the seated position, at rest
      and during 10 repeated presentations of a word generation and a constructional
      puzzle paradigm that are known to induce differential cortical activation. Due to
      its small relative change, the CBFV response can be broken down into standardized
      subcomponents describing the relative contributions of ABP, CVR, RAP, and CrCP.
      At rest and during activation, the RAP+CrCP model suggested that RAP might
      reflect myogenic activity in response to the ABP transient, whereas CrCP was more
      indicative of metabolic control. These different influences were not reflected by
      the CVR model, which indicated a predominantly metabolic response. Repeated
      measures multi-way ANOVA showed that CrCP (P = 0.025), RAP (P = 0.046), and CVR
      (P = 0.002) changed significantly during activation. CrCP also had a significant
      effect of paradigm (P = 0.045) but not hemispheric dominance. Both RAP (P =
      0.039) and CVR (P = 0.0008) had significant effects of hemispheric dominance but
      were not sensitive to the different paradigms. Subcomponent analysis can help
      with the interpretation of CBFV responses to mental activation, which were found
      to be dependent on the underlying model of the passive ABP-CBFV relationship.

PMID- 16099893
TI  - Effect of exercise, training, and glycogen availability on IL-6 receptor
      expression in human skeletal muscle.
AB  - The cytokine interleukin-6 (IL-6) exerts it actions via the IL-6 receptor (IL-6R)
      in conjunction with the ubiquitously expressed gp130 receptor. IL-6 is tightly
      regulated in response to exercise, being affected by factors such as exercise
      intensity and duration, as well as energy availability. Although the IL-6
      response to exercise has been extensively studied, little is known about the
      regulation of the IL-6R response. In the present study, we aimed to investigate
      the effect of exercise, training, and glycogen availability, factors known to
      affect IL-6, on the regulation of gene expression of the IL-6R in human skeletal
      muscle. Human subjects performed either 10 wk of training with an acute exercise
      bout before and after the training period, or a low-glycogen vs. normal-glycogen
      acute exercise trial. The IL-6R mRNA response was evaluated in both trials. In
      response to acute exercise, an increase in IL-6R mRNA levels was observed.
      Neither training nor intramuscular glycogen levels had an effect on the IL-6R
      mRNA response to exercise. However, after 10 wk of training, the skeletal muscle
      expressed a higher mRNA level of IL-6R compared with before training. The present
      study demonstrated that the IL-6R gene expression levels in skeletal muscle are
      increased in response to acute exercise, a response that is very well conserved,
      being affected by neither training status nor intramuscular glycogen levels, as
      opposed to IL-6. However, after the training period, IL-6R mRNA production was
      increased in skeletal muscle, suggesting a sensitization of skeletal muscle to IL
      6 at rest.

PMID- 16099894
TI  - Temperature dependence of speed of actin filaments propelled by slow and fast
      skeletal myosin isoforms.
AB  - It was shown that the temperature sensitivity of shortening velocity of skeletal
      muscles is higher at temperatures below physiological (10-25 degrees C) than at
      temperatures closer to physiological (25-35 degrees C) and is higher in slow than
      fast muscles. However, because intact muscles invariably express several myosin
      isoforms, they are not the ideal model to compare the temperature sensitivity of
      slow and fast myosin isoforms. Moreover, temperature sensitivity of intact
      muscles and single muscle fibers cannot be unequivocally attributed to a
      modulation of myosin function itself, as in such specimen myosin works in the
      structure of the sarcomere together with other myofibrillar proteins. We have
      used an in vitro motility assay approach in which the impact of temperature on
      velocity can be studied at a molecular level, as in such assays acto-myosin
      interaction occurs in the absence of sarcomere structure and of the other
      myofibrillar proteins. Moreover, the temperature modulation of velocity could be
      studied in pure myosin isoforms (rat type 1, 2A, and 2B and rabbit type 1 and 2X)
      that could be extracted from single fibers and in a wide range of temperatures
      (10-35 degrees C) because isolated myosin is stable up to physiological
      temperature. The data show that, at the molecular level, the temperature
      sensitivity is higher at lower (10-25 degrees C) than at higher (25-35 degrees C)
      temperatures, consistent with experiments on isolated muscles. However, slow
      myosin isoforms did not show a higher temperature sensitivity than fast isoforms,
      contrary to what was observed in intact slow and fast muscles.

PMID- 16099895
TI  - Neuropeptide Y1 receptor vasoconstriction in exercising canine skeletal muscles.
AB  - Existing evidence suggests that neuropeptide Y (NPY) acts as a neurotransmitter
      in vascular smooth muscle and is coreleased with norepinephrine from sympathetic
      nerves. We hypothesized that release of NPY stimulates NPY Y(1) receptors in the
      skeletal muscle vasculature to produce vasoconstriction during dynamic exercise.
      Eleven mongrel dogs were instrumented chronically with flow probes on the
      external iliac arteries of both hindlimbs and a catheter in one femoral artery.
      In resting dogs (n = 4), a 2.5-mg bolus of BIBP-3226 (NPY Y(1) antagonist)
      infused into the femoral artery increased external iliac conductance by 150 +/-
      82% (1.80 +/- 0.44 to 3.50 +/- 0.14 ml.min(-1).mmHg(-1); P < 0.05). A 10-mg bolus
      of BIBP-3226 infused into the femoral artery in dogs (n = 7) exercising on a
      treadmill at a moderate intensity (6 miles/h) increased external iliac
      conductance by 28 +/- 6% (6.00 +/- 0.49 to 7.64 +/- 0.61 ml.min(-1).mmHg(-1); P <
      0.05), whereas the solvent vehicle did not (5.74 +/- 0.51 to 5.98 +/- 0.43
      ml.min(-1).mmHg(-1); P > 0.05). During exercise, BIBP-3226 abolished the
      reduction in conductance produced by infusions of the NPY Y(1) agonist
      [Leu(31),Pro(34)]NPY (-19 +/- 3 vs. 0.5 +/- 1%). Infusions of BIBP-3226 (n = 7)
      after alpha-adrenergic receptor antagonism with prazosin and rauwolscine also
      increased external iliac conductance (6.82 +/- 0.43 to 8.22 +/- 0.48 ml.min(
      1).mmHg(-1); P < 0.05). These data support the hypothesis that NPY Y(1) receptors
      produce vasoconstriction in exercising skeletal muscle. Furthermore, the NPY Y(1)
      receptor-mediated tone appears to be independent of alpha-adrenergic receptor
      mediated vasoconstriction.

PMID- 16099896
TI  - Thiol supplementation in aged animals alters antioxidant enzyme activity after
      heat stress.
AB  - Declines in oxidative and thermal stress tolerance are well documented in aging
      systems. It is thought that these alterations are due in part to reductions in
      antioxidant defenses. Although intracellular thiols are major redox buffers,
      their role in maintaining redox homeostasis is not completely understood,
      particularly during aging, where the reliance on antioxidant enzymes and proteins
      may be altered. To determine whether thiol supplementation improved the
      antioxidant enzyme profile of aged animals after heat stress, young and old
      Fischer 344 rats were treated with N-acetylcysteine (NAC; 4 mmol/kg ip) 2 h
      before heat stress. Liver tissue was collected before and 0, 30, and 60 min after
      heat stress. Aging was associated with a significant decline in tissue cysteine
      and glutathione (GSH) levels. There was also an age-related decrease in copper
      zinc superoxide dismutase activity. Heat stress did not alter liver GSH,
      glutathione disulfide, or antioxidant enzyme activity. With NAC treatment, old
      animals took up more cysteine than young animals as reflected in an increase in
      liver GSH and a corresponding decrease in glutamate cysteine ligase activity.
      Catalase activity increased after NAC treatment in both age groups. Copper-zinc
      superoxide dismutase activity did not change with heat stress or drug treatment,
      whereas manganese superoxide dismutase activity was increased in old animals
      only. These data indicate that GSH synthesis is substrate limited in old animals.
      Furthermore, aged animals were characterized by large fluctuations in antioxidant
      enzyme balance after NAC treatment, suggesting a lack of fine control over these
      enzymes that may leave aged animals susceptible to subsequent stress.

PMID- 16099897
TI  - Reduced immune responses after vaccination with a recombinant herpes simplex
      virus type 1 vector in the presence of antiviral immunity.
AB  - Due to the continuous need for new vaccines, viral vaccine vectors have become
      increasingly attractive. In particular, herpes simplex virus type 1 (HSV-1)-based
      vectors offer many advantages, such as broad cellular tropism, large DNA
      packaging capacity and the induction of pro-inflammatory responses. However,
      despite promising results obtained with HSV-1-derived vectors, the question of
      whether pre-existing virus-specific host immunity affects vaccine efficacy
      remains controversial. For this reason, the influence of pre-existing HSV-1
      specific immunity on the immune response induced with a replication-defective,
      recombinant HSV-1 vaccine was investigated in vivo. It was shown that humoral as
      well as cellular immune responses against a model antigen encoded by the vaccine
      were strongly diminished in HSV-1-seropositive mice. This inhibition could be
      observed in mice infected with wild-type HSV-1 or with a replication-defective
      vector. Although these data clearly indicate that pre-existing antiviral host
      immunity impairs the efficacy of HSV-1-derived vaccine vectors, they also show
      that vaccination under these constraints might still be feasible.

PMID- 16099898
TI  - Characterization of the triplet repeats in the central domain of the gamma134.5
      protein of herpes simplex virus 1.
AB  - The gamma134.5 protein of herpes simplex virus 1 (HSV-1) consists of an amino
      terminal domain, a central domain with triplet repeats (Ala-Thr-Pro) and a
      carboxyl-terminal domain. The triplet repeats are a unique feature of the
      gamma134.5 protein encoded by HSV-1, but the number of repeats varies among
      different strains. Notably, the central domain containing the triplet repeats is
      implicated in neuroinvasion. In this report, it has been shown that partial or
      full deletion of triplet repeats, i.e. from ten to either three or zero, in the
      gamma134.5 protein has no effect on the virus response to interferon. The triplet
      deletion mutants replicate efficiently in CV-1 and mouse 10T1/2 cells. However,
      in mouse 3T6 cells, these mutants grow with delayed growth kinetics. This
      decrease in growth, compared with wild-type HSV-1(F), does not result from
      failure of the virus to suppress the RNA-dependent protein kinase response, but
      rather from a delay in virus release or egress. Accordingly, these mutant viruses
      are predominantly present within infected cells. These results indicate that
      deletions in the central domain of the gamma134.5 protein impair virus egress,
      but not virus response to interferon.

PMID- 16099899
TI  - Beta interferon and gamma interferon synergize to block viral DNA and virion
      synthesis in herpes simplex virus-infected cells.
AB  - The capacity of herpes simplex virus type 1 (HSV-1) to replicate in vitro
      decreases tremendously when animal cell cultures are exposed to ligands of both
      the alpha/beta interferon (IFN-alpha/beta) receptor and IFN-gamma receptor prior
      to inoculation with low m.o.i.s of HSV-1. However, the available evidence
      provides no insight into the possible mechanisms by which co-activation of the
      IFN-alpha/beta- and IFN-gamma-signalling pathways produces this effect.
      Therefore, it has not been possible to differentiate between whether these
      observations represent an important in vitro model of host immunological
      suppression of HSV-1 infection or an irrelevant laboratory phenomenon. Therefore,
      the current study was initiated to determine whether co-activation of the host
      cell's IFN-alpha/beta and IFN-gamma pathways either (i) induced death of HSV-1
      infected cells such that virus replication was unable to occur; or (ii) disrupted
      one or more steps in the process of HSV-1 replication. To this end, multiple
      steps in HSV-1 infection were compared in populations of Vero cells infected with
      HSV-1 strain KOS (m.o.i. of 2.5) and exposed to ligands of the IFN-alpha/beta
      receptor, the IFN-gamma receptor or both. The results demonstrated that IFN-beta
      and IFN-gamma interact in a synergistic manner to block the efficient synthesis
      of viral DNA and nucleocapsid formation in HSV-1-infected cells and do so without
      compromising host-cell viability. It was inferred that IFN-mediated suppression
      of HSV-1 replication may be a central mechanism by which the host immune system
      limits the spread of HSV-1 infection in vivo.

PMID- 16099900
TI  - Increasing seroprevalence of human herpesvirus 8 (HHV-8) with age confirms HHV-8
      endemicity in Amazon Amerindians from Brazil.
AB  - Human herpesvirus 8 (HHV-8) seroprevalences were determined in two isolated
      Amazon Amerindian tribes, according to age, gender and familial aggregation.
      Plasma and serum samples obtained from 982 Amazon Amerindians (664 Tiriyo and 318
      Waiampi) were tested for antibodies against lytic and latent HHV-8 antigens by
      using 'in-house' immunofluorescence assays. Overall, HHV-8 seroprevalence was
      56.8 % (57.4 % in the Tiriyo tribe and 55.7 % in the Waiampi tribe).
      Seroprevalence was independent of gender and increased linearly with age: it was
      35.0 % among children aged 2-9 years, 51.4 % in adolescents (10-19 years), 72.9 %
      in adults and 82.3 % in adults aged >50 years. Interestingly, 44.4 % of children
      under 2 years of age were HHV-8-seropositive. No significant differences in
      seroprevalence between tribes and age groups were detected. It is concluded that
      HHV-8 is hyperendemic in Brazilian Amazon Amerindians, with vertical and
      horizontal transmission during childhood, familial transmission and sexual
      contact in adulthood contributing to this high prevalence in these isolated
      populations.

PMID- 16099901
TI  - Functional analysis of FP25K of Helicoverpa armigera single nucleocapsid
      nucleopolyhedrovirus.
AB  - The fp25k gene of Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus
      (HearNPV) was studied. HearNPV fp25k gene transcription was found starting from
      about 18 h post-infection, and protein could be detected from the same time with
      antiserum against FP25K. To study the function of HearNPV fp25k, a recombinant
      HearNPV (HaBacWD11) with an enhanced green fluorescent protein (GFP) gene
      replacing the fp25k was constructed using HaBacHZ8, a bacmid of HearNPV that
      lacks the polyhedrin gene. Growth curve analysis showed that HaBacWD11 produced
      higher titres of budded viruses (BVs) than its wild-type counterpart HaBacHZ8
      GFP. Electron microscopic analysis indicated that at the late stage of infection,
      the number of intranuclear enveloped nucleocapsids in HaBacWD11-infected cells
      was much less than that of HaBacHZ8-GFP. A rescue recombinant virus HaBacWD14 was
      constructed by reintroducing fp25k gene into HaBacWD11. The growth curve and
      electron microscopic analysis of the rescued recombinant confirmed that the
      increase of BV yield and the decrease of the virion production in infected cells
      were the result of fp25k deletion. The expression of membrane fusion protein
      (Ha133) and ODV-E66 were studied using the FP25K mutants HaBacWD11 and HaBacHZ8
      GFP. Unlike FP25K mutants in Autographa californica multicapsid NPV (AcMNPV),
      which caused an increase in the expression of membrane fusion protein GP64 and a
      decrease of ODV-E66, no obvious changes at the expression level of Ha133 and ODV
      E66 were observed in HearNPV FP25K mutant.

PMID- 16099902
TI  - In vivo depletion of CD8+ T lymphocytes abrogates protective immunity to African
      swine fever virus.
AB  - To understand the mechanisms involved in protective immunity to African swine
      fever virus (ASFV) infection, the observation that infection with the avirulent
      Portuguese ASFV isolate OUR/T88/3 protects outbred pigs from challenge with the
      virulent Portuguese ASFV isolate OUR/T88/1 was exploited. It was demonstrated
      that pigs exposed to OUR/T88/3 and then depleted of CD8+ lymphocytes were no
      longer fully protected from OUR/T88/1 challenge. This indicated that CD8+
      lymphocytes play an important role in the protective immune response to ASFV
      infection and that anti-ASFV antibody alone, from OUR/T88/3 infection, was not
      sufficient to protect pigs from OUR/T88/1 challenge. Inbred pigs of the cc
      haplotype infected with OUR/T88/3 were not always protected from OUR/T88/1
      challenge and developed both viraemia and fever. Such viraemia was always
      correlated with increased numbers of circulating CD8beta+ lymphocytes, indicating
      a specific role for CD8beta+ lymphocytes in combating viraemia. These experiments
      indicate an important role for CD8+ lymphocytes, particularly CD8beta+
      lymphocytes, in ASF protective immunity.

PMID- 16099903
TI  - T1764G1766 core promoter double mutants are restricted to Hepatitis B virus
      strains with an A1757 and are common in genotype D.
AB  - To investigate the role of pre-core and basal core promoter (BCP) mutants in
      hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB) in Iran,
      Hepatitis B virus strains from 30 patients and 42 anti-HBe-positive asymptomatic
      carriers (ASCs) were characterized. G1896A pre-core stop mutants, detected in 77
      % of e-CHB patients and 85 % of ASCs, showed no association with virus load or
      aminotransferase levels. Twenty per cent of e-CHB patients and 31 % of ASCs
      harboured T1762A1764 mutants. When this double mutation was associated with
      G1757, it was linked to a higher virus load in patients than when it was
      associated with A1757 (10(5.2+/-1.8) vs 10(3.2+/-0.8) copies ml(-1); P=0.004).
      Interestingly, the most common BCP mutations were T1764 and G1766, which were
      present in 33 % of e-CHB patients and 29 % of ASCs. These were associated with
      higher virus load and aminotransferase levels compared with patients lacking core
      promoter mutations, although this was not significant. The T1764G1766 double
      mutation was only present in strains with A1757 (P<0.001), which is more frequent
      in strains of genotype D than in those belonging to other genotypes. On the other
      hand, the T1762A1764 double mutation was found more frequently in association
      with G1757 than with A1757. The T1762A1764 double mutation forms a binding site
      for hepatocyte nuclear factor 1 (HNF1), which is constrained by A1757. However,
      the T1764G1766 double mutant may form a binding site for HNF3. Thus, position
      1757 affects the emergence of promoter double mutants and would predict a
      relative genotypic restriction of both the T1762A1764 and the T1764G1766 double
      mutants.

PMID- 16099904
TI  - Differential splicing of E6 within human papillomavirus type 18 variants and
      functional consequences.
AB  - Persistent infections of the uterine cervix with 'high-risk' human papillomavirus
      (HPV) are now recognized as necessary for the development of cervical cancer.
      Among them, HPV types 16 and 18 exhibit numerous variants associated with
      different risks for cervical cancer development. In this study, the questions of
      whether different HPV type 18 variants exhibit changes in early gene
      transcription and the molecular mechanisms underlying these differences were
      investigated. It was shown that, indeed, type 18 variants exhibited singular
      differences in E6 transcripts in vivo. Higher levels of the E6*I transcript were
      detected regularly in clones harbouring the African variant, as opposed to low
      levels of this transcript detected in clones containing the reference clone
      (Asian-Amerindian), where significantly higher levels of full-length E6
      transcript were usually observed. As a direct consequence, higher levels of p53
      protein were found in the presence of African E6, as opposed to the low levels of
      p53 observed with the Asian-Amerindian E6. These variations in consequence
      affected the levels of cellular proteins regulated by p53, such as Bax. Similar
      changes in the relative levels of E6 transcripts were observed when tumours
      containing type 18 E6 variants were analysed. The different ability of cells
      containing variant E6 genes to form tumours in nude mice was suggested by the
      fact that tumour volumes were considerably higher when cells expressed the Asian
      Amerindian E6. Mutagenesis analysis of the reference clone showed that a C491A
      change reverts the phenotype. These results suggest that different splicing
      patterns of E6 within HPV type 18 variants may possibly have biological
      implications in viral tumorigenesis.

PMID- 16099905
TI  - Increase in infectivity of targeted Moloney murine leukemia virus-based gene
      delivery vectors through lowering the threshold for fusion.
AB  - Many research groups have developed targeted vectors for gene therapy based on
      Moloney murine leukemia virus (MoMLV). Despite proper binding of the targeted
      vector to the target molecule, little or no infectivity of human cells expressing
      the target molecule has been achieved in most studies. One of the reasons for
      this lack of infectivity may be steric hindrance within the targeted envelope
      glycoprotein (Env), impeding the conformational changes required for fusion and
      infection. Here, attempts were made to solve this problem by mutating key
      residues within Env of two targeted MoMLV-based vectors, MoMLV-E-Sel and MoMLV
      FBP. Selection of key residues was based on an Env with reduced threshold for
      fusion, that of the CD4-independent human immunodeficiency virus type 2 isolate
      ROD/B. It was shown here that vectors bearing MoMLV-FBP Env with a V512M
      substitution had higher titres and faster kinetics of entry than vectors bearing
      parental targeted Env proteins. This could be due to the partial release of
      steric constraints that result in an Env with a reduced threshold for fusion.

PMID- 16099906
TI  - Yeast system as a model to study Moloney murine leukemia virus integrase:
      expression, mutagenesis and search for eukaryotic partners.
AB  - Moloney murine leukemia virus (M-MuLV) integrase (IN) catalyses the insertion of
      the viral genome into the host chromosomal DNA. The limited solubility of the
      recombinant protein produced in Escherichia coli led the authors to explore the
      use of Saccharomyces cerevisiae for expression of M-MuLV IN. IN was expressed in
      yeast and purified by chromatography on nickel-NTA agarose. IN migrated as a
      single band in SDS-PAGE and did not contain IN degradation products. The enzyme
      was about twofold more active than the enzyme purified from E. coli and was free
      of nucleases. Using the yeast system, the substitution of the putative catalytic
      amino acid Asp184 by alanine was also analysed. The mutated enzyme was inactive
      in the in vitro assays. This is the first direct demonstration that mutation of
      Asp184 inactivates M-MuLV IN. Finally, S. cerevisiae was used as a model to
      assess the ability of M-MuLV IN to interact with eukaryotic protein partners. The
      expression of an active M-MuLV IN in yeast strains deficient in RAD52 induced a
      lethal effect. This phenotype could be attributed to cellular damage, as
      suggested by the viability of cells expressing inactive D184A IN. Furthermore,
      when active IN was expressed in a yeast strain lacking the ySNF5 transcription
      factor, the lethal effect was abolished, suggesting the involvement of ySNF5 in
      the cellular damage induced by IN. These results indicate that S. cerevisiae
      could be a useful model to study the interaction of IN with cellular components
      in order to identify potential counterparts of the natural host.

PMID- 16099907
TI  - Extensive editing of a small fraction of human T-cell leukemia virus type 1
      genomes by four APOBEC3 cytidine deaminases.
AB  - In the absence of the human immunodeficiency virus type 1 (HIV-1) Vif protein,
      the host-cell cytidine deaminases APOBEC3F and -3G are co-packaged along with
      virion RNA. Upon infection of target cells, nascent single-stranded DNA can be
      edited extensively, invariably giving rise to defective genomes called G-->A
      hypermutants. Although human T-cell leukemia virus type 1 (HTLV-1) replicates in
      the same cell type as HIV-1, it was shown here that HTLV-1 is relatively
      resistant to the antiviral effects mediated by human APOBEC3B, -3C, -3F and -3G.
      Nonetheless, a small percentage of genomes (0.1<f<5 %) were edited extensively:
      up to 97 % of cytidine targets were deaminated. In contrast, hypermutated HTLV-1
      genomes were not identified in peripheral blood mononuclear cell DNA from ten
      patients with non-malignant HTLV-1 infection. Thus, although HTLV-1 DNA can
      indeed be edited by at least four APOBEC3 cytidine deaminases in vitro, they are
      conspicuously absent in vivo.

PMID- 16099908
TI  - Evaluation of live feline immunodeficiency virus vaccines with modified antigenic
      properties.
AB  - Live-attenuated viruses have typically been generated from pathogenic viruses by
      genetic modifications that modified their replicative capacity. The present study
      investigated whether modification of the antigenic properties of live-attenuated
      viruses might improve upon the protection that such vaccines afford against
      lentivirus infection. In a previous study, random amino acid substitutions were
      introduced into the transmembrane envelope glycoprotein of the feline
      immunodeficiency virus (FIV), within a highly conserved domain (principal
      immunodominant domain) bearing immunodominant B-cell epitopes. Amongst a wide set
      of mutants, mutations that modified antibody specificity without abolishing
      infectivity ex vivo were selected. In the present study, two such mutants, TN14
      and TN92, were evaluated for their replicative capacities and pathogenic
      properties in vivo in comparison with the parental virus, FIV 34TF10. No
      significant differences in viral load were observed between mutant and parental
      viruses. After 1 year of infection, all animals were subjected to a heterologous
      intraclade superinfection with a primary strain of FIV. Whilst both parental and
      modified viruses protected cats from high viral loads after superinfection, the
      TN92 virus afforded a higher degree of protection (P=0.0079). Such improvement in
      protection might correlate with a decrease in the immunogenicity of a B-cell
      epitope potentially involved in antibody enhancement of infection.

PMID- 16099909
TI  - Analysis of the binding of hepatitis C virus genotype 1a and 1b E2 glycoproteins
      to peripheral blood mononuclear cell subsets.
AB  - Hepatitis C virus (HCV) binding to hepatocytes is thought to be mediated via
      interaction of the E2 glycoprotein with (co-)receptors including CD81 and
      scavenger receptor class B type I (SR-BI). Here, the expression of CD81 and SR-BI
      was analysed on peripheral blood mononuclear cell (PBMC) subsets, and the binding
      of genotype 1 soluble truncated E2 (sE2) proteins to these cells was
      investigated. All PBMC subsets expressed CD81, although at varying levels. In
      contrast, SR-BI was only detected on monocytes and dendritic cells (DCs). The
      genotype 1a H77c sE2 protein showed higher PBMC binding than other genotype 1a/b
      sE2s. H77c sE2 binding to different PBMC subsets largely paralleled their level
      of CD81 expression, and could be inhibited by blocking E2-CD81 interaction.
      However, those PBMC subsets reported to be infected by HCV in vivo (monocytes,
      DCs and B cells) also exhibited residual, CD81-independent binding, indicating
      roles for SR-BI/other receptor(s) in mediating haematopoietic cell infection.

PMID- 16099910
TI  - Antiviral effect of dehydroepiandrosterone on Japanese encephalitis virus
      infection.
AB  - Japanese encephalitis virus (JEV), which causes neurological disorders, completes
      its life cycle and triggers apoptotic cell death in infected cells.
      Dehydroepiandrosterone (DHEA), an adrenal-derived steroid, has been implicated in
      protection against neurotoxicity and protection of animals from viral-induced
      encephalitis, resulting in an increased survival rate of the animals. Currently,
      the mechanisms underlying the beneficial effects of DHEA against the virus are
      largely unknown. In this study, DHEA suppression of JEV replication and virus
      induced apoptosis in murine neuroblastoma (N18) cells was investigated. It was
      found that DHEA suppressed JEV-induced cytopathic effects, JEV-induced apoptotic
      cell death and JEV propagation in a concentration-dependent manner. Antiviral
      activity was more efficient in cultures treated with DHEA immediately after viral
      adsorption compared with that in cultures receiving delayed administration after
      adsorption or transient exposure before adsorption. JEV-induced cytotoxicity was
      accompanied by the inactivation of extracellular signal-regulated protein kinase
      (ERK). Inactivation of ERK by JEV infection was reversed by DHEA. When cells were
      treated with the ERK inhibitor U0126, DHEA lost its antiviral effect. Activation
      of ERK by anisomycin mimicked the action of DHEA in suppressing JEV-induced
      cytotoxicity. DHEA-related compounds, such as its sulfate ester (DHEAS) and
      pregnenolone, were unable to suppress JEV-induced cytotoxicity and ERK
      inactivation. The hormone-receptor antagonists ICI 182780 and flutamide failed to
      abrogate the antiviral effect of DHEA. These findings suggest that the antiviral
      effect of DHEA is not linked directly to the genomic steroid-receptor pathways
      and suggest that the signalling pathways of ERK play a role in the antiviral
      action of DHEA.

PMID- 16099911
TI  - Identification of classical swine fever virus protein E2 as a target for
      cytotoxic T cells by using mRNA-transfected antigen-presenting cells.
AB  - Vaccination of pigs against Classical swine fever virus (CSFV) by using live
      virus vaccines induces early protection before detectable humoral immune
      responses. Immunological analyses indicate that this is associated with T-cell
      activation, underlining the importance of targeting cytotoxic T-lymphocyte (CTL)
      responses for vaccine improvement. Antigen-presenting cells (APCs) transfected
      with mRNA encoding structural protein E2 or non-structural viral proteins NS3
      NS4A were used to identify viral genes encoding CTL epitopes. Monocyte-derived
      dendritic cells (DCs) and fibrocytes served as the APCs. In vitro translation of
      the mRNA and microscopic analysis of transfected cells demonstrated that E2 and
      NS3-NS4A could be identified. APCs transfected with either of the mRNA molecules
      restimulated CSFV-specific T cells to produce gamma interferon and specific
      cytotoxic activity against CSFV-infected target cells. The presence of CTL
      epitopes on E2 was confirmed by using d/d-haplotype MAX cells expressing E2
      constitutively as target cells in d/d-haplotype CTL assays. A potent CTL activity
      against E2 was detected early (1-3 weeks) after CSFV challenge. This work
      corroborates the existence of CTL epitopes within the non-structural protein
      domain NS3-NS4A of CSFV. Furthermore, epitopes on the E2 protein can also now be
      classified as targets for CTLs, having important implications for vaccine design,
      especially subunit vaccines. As for the use of mRNA-transfected APCs, this
      represents a simple and efficient method to identify viral genes encoding CTL
      epitopes in outbred populations.

PMID- 16099912
TI  - Mannose-binding lectin binds to Ebola and Marburg envelope glycoproteins,
      resulting in blocking of virus interaction with DC-SIGN and complement-mediated
      virus neutralization.
AB  - Mannose-binding lectin (MBL), a serum lectin that mediates innate immune
      functions including activation of the lectin complement pathway, binds to
      carbohydrates expressed on some viral glycoproteins. In this study, the ability
      of MBL to bind to virus particles pseudotyped with Ebola and Marburg envelope
      glycoproteins was evaluated. Virus particles bearing either Ebola (Zaire strain)
      or Marburg (Musoke strain) envelope glycoproteins bound at significantly higher
      levels to immobilized MBL compared with virus particles pseudotyped with
      vesicular stomatitis virus glycoprotein or with no virus glycoprotein. As
      observed in previous studies, Ebola-pseudotyped virus bound to cells expressing
      the lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3
      grabbing non-integrin). However, pre-incubation of virus with MBL blocked DC-SIGN
      mediated binding to cells, suggesting that the two lectins bind at the same or
      overlapping sites on the Ebola glycoprotein. Neutralization experiments showed
      that virus pseudotyped with Ebola or Marburg (Musoke) glycoprotein was
      neutralized by complement, while the Marburg (Ravn strain) glycoprotein
      pseudotyped virus was less sensitive to neutralization. Neutralization was
      partially mediated through the lectin complement pathway, since a complement
      source deficient in MBL was significantly less effective at neutralizing viruses
      pseudotyped with filovirus glycoproteins and addition of purified MBL to the MBL
      deficient complement increased neutralization. These experiments demonstrated
      that MBL binds to filovirus envelope glycoproteins resulting in important
      biological effects and suggest that MBL can interact with filoviruses during
      infection in humans.

PMID- 16099913
TI  - Stable trimerization of recombinant rabies virus glycoprotein ectodomain is
      required for interaction with the p75NTR receptor.
AB  - Native rabies virus glycoprotein (RVGvir) is a trimeric, membrane-anchored
      protein that has been shown to interact with the p75NTR neurotrophin receptor. In
      order to determine if the RVG trimeric oligomerization state is required for its
      binding with p75NTR, different soluble recombinant molecules containing the
      entire RVG ectodomain (RVGect) were expressed alone or fused at its C terminus to
      the trimerization domain of the bacteriophage T4 fibritin, termed 'foldon'. The
      oligomerization status of recombinant RVG was investigated using sedimentation in
      sucrose gradient and p75NTR binding assays. It was found that, in the absence of
      the fibritin foldon, recombinant RVGect forms unstable trimers that dissociate
      into monomers in a concentration-dependent manner. C-terminal fusion with the
      foldon induces stable RVG trimerization, which is concentration-independent.
      Furthermore, the fibritin foldon maintains the native antigenic structure of the
      carboxy part of RVGect. Cell binding experiments showed that RVG trimerization is
      required for efficient interaction with p75NTR. However, the exact mode of
      trimerization appears unimportant, as trimeric recombinant RVGect (fused to the
      fibritin foldon) and RVGvir both recognize p75NTR with similar nanomolar
      affinities, as shown by surface plasmon resonance experiments. Altogether, these
      results show that the C-terminal fusion of the RVG ectodomain with the fibritin
      foldon is a powerful way to obtain a recombinant trimeric native-like structure
      of the p75NTR binding domain of RVG.

PMID- 16099914
TI  - Early endocytosis pathways in SSN-1 cells infected by dragon grouper nervous
      necrosis virus.
AB  - Many fish undergo betanodavirus infection. To study the infection process of
      dragon grouper nervous necrosis virus (DGNNV), native virus and virus-like
      particles (VLPs) were used to analyse the binding and internalization in SSN-1
      cells. The binding of DGNNV and VLPs to SSN-1 cells was demonstrated using
      Western blotting and immunofluorescence microscopy. As estimated by indirect
      ELISA, the DGNNV particles bound SSN-1 cells in a dose-dependent manner up to 8 x
      10(4) particles per cell. The binding of VLPs was sensitive to neuraminidase and
      tunicamycin, suggesting that cell-surface sialic acid is involved in binding. The
      penetration of DGNNV into cells, which was monitored by electron microscopy,
      appeared to occur mainly via the spherical pit and membrane ruffling pathways.
      Occasionally, a spherical pit was engulfed by membrane ruffling so as to form a
      large figure-of-eight-shaped vesicle with an open connection. Our observations
      suggest that DGNNV utilizes both micro- and macropinocytosis pathways to enter
      SSN-1 cells.

PMID- 16099915
TI  - Identification and real-time PCR quantification of Phocine distemper virus from
      two colonies of Scottish grey seals in 2002.
AB  - The North Sea European harbour seal (Phoca vitulina) population has endured two
      phocine distemper virus (PDV) epidemics in 1988 and 2002. The grey seal
      (Halichoerus grypus) is a sympatric seal species that shows little or no
      mortality from PDV. Two Scottish grey seal breeding colonies were sampled for
      evidence of PDV infection approximately 2 months after the peak of the 2002
      epidemic. In both colonies, a proportion of mothers (13/109) and pups (6/84)
      tested positive for PDV in their leukocytes. All infected animals were
      asymptomatic and completed the breeding season successfully. These results
      illustrate that grey seals come into contact with infectious seals and can become
      infected themselves without experiencing acute effects. In some seals the virus
      is able to replicate from the primary site of infection. This study provides
      evidence that grey seals may have an active role in the spread of PDV during an
      epidemic.

PMID- 16099916
TI  - Molecular characterization of the major capsid protein VP6 of bovine group B
      rotavirus and its use in seroepidemiology.
AB  - The major inner capsid protein (VP6) gene of the bovine group B rotavirus (GBR)
      Nemuro strain is 1269 nt in length and contains one open reading frame encoding
      391 aa. Nucleotide and amino acid sequence identities of the Nemuro VP6 gene
      compared with the published corresponding human and rodent GBR genes were
      respectively 66-67 and 70-72 %, which are notably lower than those between human
      and rodent viruses (72-73 and 83-84 %, respectively). Overall identities of VP6
      genes among GBRs were substantially lower than those among both group A
      rotaviruses (GARs) and group C rotaviruses (GCRs) derived from different species
      of mammals. These results demonstrate that bovine GBR is remarkably distinct from
      other GBRs and that GBRs from different species may have had a longer period of
      divergence than GARs and GCRs. Recombinant VP6 was generated with a baculovirus
      expression system and used for an ELISA to detect GBR antibodies. All 13 paired
      sera from adult cows with GBR-induced diarrhoea in the field showed antibody
      responses in the ELISA. In serological surveys of GBR infection using the ELISA,
      47 % of cattle sera were positive for GBR antibodies, with a higher antibody
      prevalence in adults than in young cattle. In pigs, a high prevalence of GBR
      antibodies (97 %) was detected in sera from sows. These results suggest that GBR
      infection is common in cattle and pigs, notwithstanding the scarcity of reports
      of GBR detection in these species to date.

PMID- 16099917
TI  - Analysis of the epidemiological dynamics during the 1982-1983 epidemic of foot
      and-mouth disease in Denmark based on molecular high-resolution strain
      identification.
AB  - An epidemic of foot-and-mouth disease (FMD) causing a total of 23 cases in 1982
      1983, primarily on the island of Funen, Denmark, was subjected to molecular
      epidemiological investigations. In an attempt to exploit the quasi-species nature
      of foot-and-mouth disease virus strains for molecular high-resolution strain
      identification in order to analyse the dynamics of this epidemic, full-length VP1
      coding regions were sequenced for 17 isolates collected at different farms during
      the epidemic. The sequence information together with epidemiological information
      gathered during the epidemic suggests that the epidemic was caused by at least
      three introductions across Danish borders and one case of airborne transmission
      between two islands in Denmark over a distance of 70 km. The assortment of
      nucleotide markers among the three strains is indicative of common recombination
      events in their evolutionary history, and the prerequisite of co- or
      superinfection of animals with variant strains in turn implies that they have a
      common source or epidemiologically related sources originating from an area with
      endemic FMD.

PMID- 16099918
TI  - Construction and characterization of infectious cDNA clones of a chicken strain
      of hepatitis E virus (HEV), avian HEV.
AB  - Hepatitis E virus (HEV), the causative agent of hepatitis E, is an important
      human pathogen. Increasing evidence indicates that hepatitis E is a zoonosis.
      Avian HEV was recently discovered in chickens with hepatitis-splenomegaly
      syndrome in the USA. Like swine HEV from pigs, avian HEV is also genetically and
      antigenically related to human HEV. The objective of this study was to construct
      and characterize an infectious cDNA clone of avian HEV for future studies of HEV
      replication and pathogenesis. Three full-length cDNA clones of avian HEV, pT7
      aHEV-5, pT7G-aHEV-10 and pT7G-aHEV-6, were constructed and their infectivity was
      tested by in vitro transfection of leghorn male hepatoma (LMH) chicken liver
      cells and by direct intrahepatic inoculation of specific-pathogen-free (SPF)
      chickens with capped RNA transcripts from the three clones. The results showed
      that the capped RNA transcripts from each of the three clones were replication
      competent when transfected into LMH cells as demonstrated by detection of viral
      antigens with avian HEV-specific antibodies. SPF chickens intrahepatically
      inoculated with the capped RNA transcripts from each of the three clones
      developed active avian HEV infections as evidenced by seroconversion to avian HEV
      antibodies, viraemia and faecal virus shedding. The infectivity was further
      confirmed by successful infection of naive chickens with the viruses recovered
      from chickens inoculated with the RNA transcripts. The results indicated that all
      three cDNA clones of avian HEV are infectious both in vitro and in vivo. The
      availability of these infectious clones for a chicken strain of HEV now affords
      an opportunity to study the mechanisms of HEV cross-species infection and tissue
      tropism by constructing chimeric viruses among human, swine and avian HEVs.

PMID- 16099919
TI  - HcPro, a multifunctional protein encoded by a plant RNA virus, targets the 20S
      proteasome and affects its enzymic activities.
AB  - The proteasome is a multicatalytic complex involved in many cellular processes in
      eukaryotes, such as protein and RNA turnover, cell division, signal transduction,
      transcription and translation. Intracellular pathogens are targets of its enzymic
      activities, and a number of animal viruses are known to interfere with these
      activities. The first evidence that a plant virus protein, the helper component
      proteinase (HcPro) of Lettuce mosaic virus (LMV; genus Potyvirus), interferes
      with the 20S proteasome ribonuclease is reported here. LMV infection caused an
      aggregation of the 20S proteasome to high-molecular mass structures in vivo, and
      specific binding of HcPro to the proteasome was confirmed in vitro using two
      different approaches. HcPro inhibited the 20S endonuclease activity in vitro,
      while its proteolytic activities were unchanged or slightly stimulated. This
      ability of HcPro, a pathogenicity regulator of potyviruses, to interfere with
      some of the catalytic functions of the 20S proteasome suggests the existence of a
      novel type of defence and counter-defence interplay in the course of interaction
      between potyviruses and their hosts.

PMID- 16099920
TI  - An internal RNA element in the P3 cistron of Wheat streak mosaic virus revealed
      by synonymous mutations that affect both movement and replication.
AB  - Multiple synonymous substitution mutations in the Wheat streak mosaic virus P3
      cistron did not affect translation in vitro but rendered the virus incapable of
      systemic infection. Multiple synonymous substitutions in the cylindrical
      inclusion cistron did not alter infectivity or in vitro translation. To assess
      replication and movement phenotypes, P3 mutations were placed in context with a
      GUS reporter gene. GUS activity measured in barley protoplasts 36 h post
      transfection indicated that mutants with synonymous substitutions in P3 retained
      the ability to replicate at 22-80 % of wild-type levels. Almost no GUS activity
      was detected in protoplasts transfected with a P3 frame-shift mutant.
      Histochemical GUS assays conducted 3 days post-inoculation (p.i.) revealed
      genomes with multiple synonymous substitutions in P3, which were able to
      establish infection foci limited to small clusters of cells that increased in
      size only slightly by 5 days p.i. Infection foci produced by wild-type Wheat
      streak mosaic virus-expressing GUS were much larger at 3 days p.i. and had
      coalesced by 5 days p.i. No GUS activity was detected in plants inoculated with
      the frame-shift mutant bearing GUS. Three of four mutants, each with a single
      synonymous substitution in the 3'-proximal half of the P3 cistron, were wild-type
      with respect to systemic infectivity. A model RNA secondary structure obtained
      for the region was disrupted by the debilitating single mutation but not by the
      other three single mutations. Collectively, these results identify an internal
      RNA sequence element in the P3 cistron that affects both replication and movement
      of the viral genome.

PMID- 16099921
TI  - Specific and common changes in Nicotiana benthamiana gene expression in response
      to infection by enveloped viruses.
AB  - Microarrays derived from Solanum tuberosum expressed sequence tags were used to
      test the hypothesis that genetically distinct enveloped viruses elicit unique
      changes in Nicotiana benthamiana gene expression. The results of our study, which
      included Sonchus yellow net virus (SYNV), a plant rhabdovirus that replicates in
      the nucleus of infected cells, and Impatiens necrotic spot virus (INSV), a plant
      bunyavirus that replicates in the cytoplasm, were consistent with this
      hypothesis. Statistically significant changes (P< or =0.01) in the expression of
      275, 2646 and 4165 genes were detected in response to INSV at 2, 4 and 5 days
      post-inoculation (d.p.i.), respectively. In contrast, 35, 665 and 1458 genes were
      expressed differentially in response to SYNV at 5, 11 and 14 d.p.i.,
      respectively. The microarray results were verified by Northern hybridization
      using a subset of these genes as probes. Notably, INSV, but not SYNV, induced
      expression of small heat-shock protein genes to high levels. In contrast to SYNV,
      infection by INSV resulted in downregulation of all histone genes, of which the
      downregulation of histone 2b expression to very low levels was confirmed by
      Northern hybridization. The expression of a putative WRKY transcription factor at
      11 d.p.i., but not at 5 or 14 d.p.i., in SYNV-infected tissue suggested that the
      temporal response to virus infection was identified readily using our
      experimental design. Overall, infection by INSV resulted in larger fold changes
      in host gene expression relative to infection by SYNV. Taken together, the
      present data demonstrate differential responses of a common host to two
      genetically distinct viruses.

PMID- 16099922
TI  - Sheep scrapie susceptibility-linked polymorphisms do not modulate the initial
      binding of cellular to disease-associated prion protein prior to conversion.
AB  - Conversion of the host-encoded protease-sensitive cellular prion protein (PrPC)
      into the scrapie-associated protease-resistant isoform (PrPSc) of prion protein
      (PrP) is the central event in transmissible spongiform encephalopathies or prion
      diseases. Differences in transmissibility and susceptibility are largely
      determined by polymorphisms in PrP, but the exact molecular mechanism behind PrP
      conversion and the modulation by disease-associated polymorphisms is still
      unclear. To assess whether the polymorphisms in either PrPC or PrPSc modulate the
      initial binding of PrPC to PrPSc, several naturally occurring allelic variants of
      sheep PrPC and PrPSc that are associated with differential scrapie susceptibility
      and transmissibility [the phylogenetic wild-type (ARQ), the codon 136Val variant
      (VRQ) and the codon 171Arg variant (ARR)] were used. Under cell-free PrP
      conversion conditions known to reproduce the observed in vivo differential
      scrapie susceptibility, it was found that the relative amounts of PrPC allelic
      variants bound by various allelic PrPSc variants are PrP-specific and have
      comparable binding efficiencies. Therefore, the differential rate-limiting step
      in conversion of sheep PrP variants is not determined by the initial PrPC-PrPSc
      binding efficiency, but seems to be an intrinsic property of PrPC itself.
      Consequently, a second step after PrPC-PrPSc-binding should determine the
      observed differences in PrP conversion efficiencies. Further study of this second
      step may provide a future tool to determine the mechanism underlying refolding of
      PrPC into PrPSc and supports the use of conversion-resistant polymorphic PrPC
      variants as a potential therapeutic approach to interfere with PrP conversion in
      transmissible spongiform encephalopathy development.

PMID- 16099923
TI  - PrP glycoforms are associated in a strain-specific ratio in native PrPSc.
AB  - Prion diseases involve conversion of host-encoded cellular prion protein (PrPC)
      to a disease-related isoform (PrPSc). Using recombinant human beta-PrP, a panel
      of monoclonal antibodies was produced that efficiently immunoprecipitated native
      PrPSc and recognized epitopes between residues 93-105, indicating for the first
      time that this region is exposed in both human vCJD and mouse RML prions. In
      contrast, monoclonal antibodies raised to human alpha-PrP were more efficient in
      immunoprecipitating PrPC than PrPSc, and some of them could also distinguish
      between different PrP glycoforms. Using these monoclonal antibodies, the physical
      association of PrP glycoforms was studied in normal brain and in the brains of
      humans and mice with prion disease. It was shown that while PrPC glycoforms can
      be selectively immunoprecipitated, the differentially glycosylated molecules of
      native PrPSc are closely associated and always immunoprecipitate together.
      Furthermore, the ratio of glycoforms comprising immunoprecipitated native PrPSc
      from diverse prion strains was similar to those observed on denaturing Western
      blots. These studies are consistent with the view that the proportion of each
      glycoform incorporated into PrPSc is probably controlled in a strain-specific
      manner and that each PrPSc particle contains a mixture of glycoforms.

PMID- 16099924
TI  - Formation of tamoxifen-DNA adducts via O-sulfonation, not O-acetylation, of alpha
      hydroxytamoxifen in rat and human livers.
AB  - Tamoxifen (TAM) is used as the standard endocrine therapy for breast cancer
      patients and as a chemopreventive agent for women at high risk for this disease.
      Unfortunately, treatment of TAM increases the incidence of endometrial cancer;
      this may be due to the genotoxic damage induced by TAM metabolites. Formation of
      TAM-DNA adducts in rat liver correlates with the development of hepatocarcinoma.
      TAM-DNA adducts are proposed to be formed through O-sulfonation and/or O
      acetylation of alpha-hydroxylated TAM and its metabolites. However, the role of O
      sulfonation and O-acetylation in the formation of TAM-DNA adducts has not been
      extensively investigated. Rat or human hydroxysteroid sulfotransferases (HST),
      acetyltransferases, and liver cytosol were incubated with calf thymus DNA, alpha
      OHTAM, and either 3'-phosphoadenosine 5'-phosphosulfate (PAPS) or acetyl coenzyme
      A (acetyl-CoA) as a cofactor and analyzed for TAM-DNA adduct formation, using 32P
      postlableling/polyacrylamide gel electrophoresis analysis. TAM-DNA adduct was
      formed when PAPS, not acetyl-CoA, was used. No TAM-DNA adducts were produced
      using human N-acetyltransferase I and II. HST antibody inhibited approximately
      90% of TAM-DNA adduct formation generated by the cytosol or HST, suggesting that
      HST is primarily involved in the formation of TAM-DNA adducts. The formation of
      TAM-DNA adducts with rat liver cytosol and HST was much higher than that of human
      liver cytosol and HST. Our results indicate that TAM-DNA adducts are formed via O
      sulfonation, not O-acetylation, of alpha-hydroxylated TAM and its metabolites.

PMID- 16099925
TI  - Cocaine- and amphetamine-regulated transcript (CART) peptides modulate the
      locomotor and motivational properties of psychostimulants.
AB  - Drug addiction results from a subversion of neural circuits that control
      motivation. Although the hedonic and addictive properties of psychostimulants and
      drugs of abuse are predominantly attributed to dopamine and glutamate, it is
      appreciated that other signaling molecules in the brain are important. This study
      suggests that cocaine- and amphetamine-regulated transcript (CART) peptides
      modulate the locomotor and motivational properties of psychostimulants. The
      behavioral effects of cocaine and amphetamine were examined in Carttm1Amgen
      knockout (Cart KO) and wild-type (WT) mice. Acute amphetamine administration
      increased in locomotor activity in WT mice, but this response was attenuated in
      Cart KO mice. Repeated amphetamine produced locomotor sensitization in WT mice
      but hardly any in Cart KO mice. Amphetamine elicited conditioned place preference
      in both genotypes, but amphetamine's potency was reduced in the Cart KO mice.
      Intravenous cocaine self-administration was observed in both genotypes, but Cart
      KO mice consumed less cocaine and responded less for cocaine than WT mice. The
      behavioral effects of psychostimulants were reduced in the mutant Cart KO mice.
      By contrast, open field activity and sucrose preference of drug-naive mice WT and
      Cart KO mice were not significantly different. The attenuated effects of
      amphetamine and cocaine in Cart KO mice suggest a positive neuromodulatory role
      for CART peptides in the locomotor and motivational properties of
      psychostimulants and implicate CART peptides in psychostimulant addiction.

PMID- 16099926
TI  - Functional characterization of novel allelic variants of CYP2C9 recently
      discovered in southeast Asians.
AB  - CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new
      coding variants were reported, and these variants are now named CYP2C9*14
      (R125H), CYP2C9*15 (S162X), CYP2C9*16 (T299A), CYP2C9*17 (P382S), CYP2C9*18
      (D397A), and CYP2C9*19 (Q454H). The CYP2C9*18 variant also contained an I359L
      change previously associated with the CYP2C9*3 allele. In this study, we assessed
      the functional consequences of the new coding changes. cDNAs containing each of
      the new coding changes were constructed by site-directed mutagenesis and
      expressed in a bacterial cDNA expression system, the allelic proteins were
      partially purified, and their ability to hydroxylate a prototype CYP2C9 substrate
      was assayed. Expression of cDNAs in Escherichia coli containing either the D397A
      change or the S162X (premature stop codon) could not be detected either
      spectrally or at the apoprotein level. CYP2C9.14 and CYP2C9.16 exhibited 80 to
      90% lower catalytic activity toward tolbutamide at two substrate concentrations
      compared with wild-type CYP2C9.1. Kinetic analysis confirmed that CYP2C9.14 and
      CYP2C9.16 have a higher Km and a >90% lower intrinsic clearance of tolbutamide
      compared with wild-type CYP2C9.1. Both CYP2C9.17 and CYP2C9.19 proteins exhibited
      modest 30 to 40% decreases in catalytic activity toward tolbutamide. Thus,
      CYP2C9*15 and CYP2C9*18 may represent null alleles, whereas CYP2C9*14 and
      CYP2C9*16 allelic variants produce proteins that are clearly catalytically
      defective in vitro, indicating the existence of new defective putative alleles of
      CYP2C9 in Asians.

PMID- 16099927
TI  - Gender differences in cardioprotection against ischemia/reperfusion injury in
      adult rat hearts: focus on Akt and protein kinase C signaling.
AB  - Previous studies have reported the sex differences in heart susceptibility to
      ischemia/reperfusion (I/R) injury, but the mechanisms are not understood. The
      present study tested the hypothesis that Akt and protein kinase C (PKC)epsilon
      play an important role in the sexual dimorphism of heart susceptibility to I/R
      injury. Isolated hearts from 2-month-old male and female rats were subjected to
      I/R in the Langendorff preparation. The postischemic recovery of left ventricular
      function was significantly better, and infarct size was significantly smaller in
      female (37.1 +/- 1.9%) than in male (48.3 +/- 2.3%) hearts after 25-min ischemia
      followed by 2-h reperfusion. Inhibition of phosphatidylinositol 3-kinase/Akt
      pathway by wortmannin or PKC by chelerythrine chloride before ischemia
      significantly reduced postischemic recovery and increased infarct size in female
      but not male hearts. There were no differences in myocardial protein levels of
      heat shock protein 70, Akt, and PKCepsilon, respectively, between male and female
      rats. However, the ratio of phosphorylated (p)-Akt/Akt (0.58 +/- 0.05 versus 0.22
      +/- 0.04; P < 0.05) and p-PKCepsilon/PKCepsilon (0.35 +/- 0.03 versus 0.22 +/-
      0.02; P < 0.05) was significantly higher in female than in male hearts. In
      addition, there were significant increases in p-Akt and p-PKCepsilon levels
      during reperfusion in female but not in male hearts. The results suggest that
      increased p-Akt and p-PKCepsilon levels in female hearts contribute to the gender
      related differences in heart susceptibility to I/R and play an important role in
      cardioprotection against I/R injury in females.

PMID- 16099928
TI  - Calcium-acting drugs modulate expression and development of chronic tolerance to
      nicotine-induced antinociception in mice.
AB  - Initial studies in our laboratory suggested that tolerance to nicotine is thought
      to involve neuronal adaptation not only at the level of the drug-receptor
      interaction but at postreceptor events such as calcium-dependent second
      messengers. The present study was undertaken to investigate the hypothesis that L
      type calcium channels and calcium-dependent calmodulin protein kinase II are
      involved in the development and expression of nicotine tolerance. To that end,
      the effects of modulation of L-type calcium channels (through the use of
      inhibitors or activators) as well as calcium-dependent calmodulin protein kinase
      II inactivation were studied in a mouse model of tolerance where mice were
      infused with nicotine in minipumps (24 mg/kg/day) for 14 days. In addition, the
      activity of calcium-dependent calmodulin protein kinase II in the lumbar spinal
      cord region obtained from nicotine-tolerant mice was measured. Our data showed
      that chronic administration of L-type calcium channel antagonists nimodipine (1
      and 5 mg/kg) and verapamil (10 mg/kg) prevented the development of tolerance to
      nicotine-induced antinociception. In contrast, chronic exposure of BAYK8644 [(+/
      )-1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridine
      carboxylic acid methyl ester], a calcium channel activator, enhanced nicotine's
      tolerance. Moreover, a significant increase in both dependent and independent
      calcium-dependent calmodulin protein kinase II activity was seen in the spinal
      cord in nicotine-tolerant mice. Finally, spinal administration of 1-[N,O-bis(5
      isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-phenylpiperazine (KN-62), a calcium
      dependent calmodulin protein kinase II antagonist, reduced the expression of
      tolerance to nicotine-induced antinociception in mice. In conclusion, our data
      indicate that calcium-dependent mechanisms such as L-type calcium channels and
      calcium-dependent calmodulin protein kinase II activation are involved in the
      expression and development of nicotine tolerance.

PMID- 16099929
TI  - Primaquine-induced hemolytic anemia: role of splenic macrophages in the fate of 5
      hydroxyprimaquine-treated rat erythrocytes.
AB  - Primaquine-induced hemolytic anemia is known to result from premature
      sequestration of damaged (but intact) erythrocytes by the spleen. We have shown
      previously that a phenolic metabolite, 5-hydroxyprimaquine (5-HPQ), is a direct
      acting hemolytic agent in rats, suggesting that 5-HPQ is a mediator of the
      hemolytic response to primaquine. To investigate the fate of erythrocytes in vivo
      after in vitro exposure to 5-HPQ, rat (51)Cr-labeled erythrocytes were incubated
      with hemolytic concentrations of 5-HPQ and then readministered intravenously to
      rats. The time course of loss of radioactivity from blood and uptake into the
      spleen and liver was measured. In rats given 5-HPQ-treated erythrocytes, an
      increased rate of removal of radioactivity from the circulation was observed as
      compared with the vehicle control. The loss of blood radioactivity was
      accompanied by a corresponding increase in radioactivity appearing in the spleen
      but not in the liver. When rats were pretreated with clodronate-loaded liposomes
      to deplete splenic macrophages, there was a decreased rate of removal of
      radioactivity from the circulation and a markedly diminished uptake into the
      spleen. A role for phagocytic removal of 5-HPQ-treated red cells was confirmed in
      vitro using the J774A.1 macrophage cell line. Furthermore, depletion of red cell
      GSH with diethyl maleate significantly enhanced in vitro phagocytosis of 5-HPQ
      treated red cells. The data indicate that splenic macrophages are responsible for
      removing 5-HPQ-treated red cells and support the postulate that this metabolite
      is a contributor to the hemolytic anemia induced after administration of the
      parent compound.

PMID- 16099930
TI  - The effects of extracellular purines and pyrimidines on human airway smooth
      muscle cells.
AB  - Extracellular ATP and UTP modulate the function of many cell types through the
      stimulation of specific P2 receptors, and the inhalation of UTP has been proposed
      as a therapeutic means of increasing mucociliary clearance in cystic fibrosis
      patients. The aim of this study was to determine whether P2 receptors are present
      and functional in human airway smooth muscle (HASM) cells. Experiments were
      conducted on primary cultures of HASM cells. Reverse transcription-polymerase
      chain reaction and Western blot analysis showed that P2Y(1), P2Y(2), P2Y(4), and
      P2Y(6) receptor subtypes are expressed. Exposure to extracellular ATP, UTP, ADP,
      and UDP at concentrations ranging from 10(-6) to 10(-4) M, produced significant
      increases in intracellular Ca(2+) that peaked to 491 +/- 51 nM (p < 0.001) with
      ATP 10(-5) M and to 321 +/- 30 nM with UTP 10(-4) M. ATP and UTP also induced
      HASM cell contraction, decreasing cell length by 9.9 +/- 4.3 and 5.6 +/- 2.0%,
      respectively. Pretreatment of the cells with UTP for short periods of time (10
      and 30 min) enhanced the peak Ca(2+) release to UTP, whereas repeated and
      prolonged pretreatment with UTP decreased it. These results indicate that several
      subtypes of P2Y receptors are present and functional in HASM cells. They also
      show that the response of the receptors is increased after short periods of
      exposure to UTP and decreased after prolonged and repeated exposure. Considering
      that ATP and UTP are endogenous mediators and that analogs of UTP could be used
      as a therapeutic modality, the role of extracellular triphosphate nucleotides in
      physiological and pathophysiological processes in the airways warrants further
      investigation.

PMID- 16099931
TI  - Joachim kohn (1912-1987) and the origin of cellulose acetate electrophoresis.
AB  - The year 2006 marks the 50th anniversary of the discovery of cellulose acetate
      (CA) electrophoresis by Joachim Kohn, a pathologist at Queen Mary's Hospital in
      Roehampton, London. During a career in pathology that began in 1950 and spanned
      37 years, Kohn published more than 50 papers in clinical laboratory medicine. He
      was the first to report the use of CA microbiology filters as solid supports for
      zone electrophoresis and the separation of hemoglobin phenotypes on CA membranes.
      Kohn also invented a new electrophoresis chamber and an 8-position stamp
      applicator especially for use with CA membranes. Beginning in 1957, Kohn
      pioneered the development of CA techniques for immunoelectrophoresis, counter
      immunoelectrophoresis, radial immunodiffusion, protein blotting, and
      immunofixation. He also designed a transport dressing for burn patients and was
      the first person to describe the use of an enzyme-based dipstick for measuring
      fingerstick blood glucose concentrations. This short review highlights Kohn's
      discovery of CA electrophoresis and his contributions to the development of this
      procedure.

PMID- 16099933
TI  - Lupus anticoagulants and their relationship with the inhibitors against
      coagulation factor VIII: considerations on the differentiation between the 2
      circulating anticoagulants.

PMID- 16099932
TI  - Immunoassay interference by a commonly used blood collection tube additive, the
      organosilicone surfactant silwet L-720.
AB  - BACKGROUND: A small number of immunoassays on several different types of
      analyzers were recently adversely affected by tube additives in Becton Dickinson
      (BD) Vacutainer SST, SST II, and Microtainer blood collection tubes. We examined
      the effect of a commonly used tube surfactant, Silwet L-720, on immunoassays and
      the mechanism for the interference. METHODS: Immunoassays were performed on serum
      supplemented with Silwet L-720 on the IMMULITE 2500 and AxSYM analyzers. Direct
      effects of the surfactant on the chemiluminescent detection step of immunoassays
      and on antibody immobilization on the solid phase were examined. RESULTS:
      Increasing the final surfactant concentration from 0 to 400 mg/L in serum
      significantly increased (approximately 51%) the apparent total triiodothyronine
      (TT3) concentrations measured on the IMMULITE 2500 but not the AxSYM analyzer.
      Several other competitive, but not noncompetitive, assays were also significantly
      affected by the surfactant on the IMMULITE 2500 analyzer. The effect was
      independent of serum components, and the surfactant had no direct effect on
      chemiluminescence reactions. The capture antibody, however, was displaced from
      the solid phase by incubation with solutions containing surfactant under
      conditions similar to the IMMULITE TT3 assay. CONCLUSIONS: The Silwet L-720
      surfactant, which is used to coat the inner surfaces of tubes, appears to account
      for previously reported immunoassay interference by BD Vacutainer SST blood
      collection tubes. One of the mechanisms for the interference is the desorption of
      antibodies from the solid phase by the surfactant. The results identify an
      important factor in the selection of suitable blood collection tube surfactants
      and provide an approach for solving similar tube-assay interference problems in
      the future.

PMID- 16099934
TI  - Clinical relevance of measurement of antibodies to individual snU1-RNP proteins.

PMID- 16099935
TI  - Diagnostic considerations in the measurement of human chorionic gonadotropin in
      aging women.
AB  - BACKGROUND: Human chorionic gondadotropin (hCG) screening tests are performed on
      nearly all female patients of childbearing age before any medical intervention.
      Although older women usually have negative hCG test results, positive results do
      occur and may cause clinical confusion. We examined changes with age in serum hCG
      concentrations in nonpregnant women and investigated the use of serum follicle
      stimulating hormone (FSH) measurements as an aid to interpreting higher than
      expected ("positive") hCG results. METHODS: We used 240 serum specimens for each
      of 4 female cohorts: pregnant, > or =18 years; nonpregnant, 18-40 years
      (premenopausal); nonpregnant, 41-55 years (perimenopausal); and nonpregnant, >55
      years (postmenopausal). Patients were excluded if they had an ectopic pregnancy,
      a history of trophoblastic disease or a germ-cell tumor, or if no chart was
      available for review. Quantitative hCG and FSH tests were performed on each
      specimen. RESULTS: Serum hCG concentrations in nonpregnant women increased with
      the age of the women. hCG results were higher and significantly different (P <
      0.0001) for nonpregnant women >55 years (<2.0 to 13.1 IU/L) compared with
      nonpregnant women 18-40 years (<2.0 to 4.6 IU/L) and 41-55 years (<2.0 to 7.7
      IU/L). Nineteen nonpregnant women >40 years of age had hCG concentrations > or =
      5.0 IU/L, all with an FSH concentration >32.4 IU/L. The highest FSH concentration
      in pregnancy was 7.3 IU/L. CONCLUSIONS: Serum hCG increases with age in
      nonpregnant women. A cutoff of 14.0 IU/L should be used when interpreting hCG
      results in women >55 years of age. Pregnancy is unlikely in perimenopausal women
      41-55 years of age with an hCG between 5.0 and 14.0 IU/L if serum FSH is >20.0
      IU/L.

PMID- 16099936
TI  - Integrated microfluidic compact disc device with potential use in both
      centralized and point-of-care laboratory settings.

PMID- 16099937
TI  - Analysis of albumin-associated peptides and proteins from ovarian cancer
      patients.
AB  - BACKGROUND: Albumin binds low-molecular-weight molecules, including proteins and
      peptides, which then acquire its longer half-life, thereby protecting the bound
      species from kidney clearance. We developed an experimental method to isolate
      albumin in its native state and to then identify [mass spectrometry (MS)
      sequencing] the corresponding bound low-molecular-weight molecules. We used this
      method to analyze pooled sera from a human disease study set (high-risk persons
      without cancer, n = 40; stage I ovarian cancer, n = 30; stage III ovarian cancer,
      n = 40) to demonstrate the feasibility of this approach as a discovery method.
      METHODS: Albumin was isolated by solid-phase affinity capture under native
      binding and washing conditions. Captured albumin-associated proteins and peptides
      were separated by gel electrophoresis and subjected to iterative MS sequencing by
      microcapillary reversed-phase tandem MS. Selected albumin-bound protein fragments
      were confirmed in human sera by Western blotting and immunocompetition. RESULTS:
      In total, 1208 individual protein sequences were predicted from all 3 pools. The
      predicted sequences were largely fragments derived from proteins with diverse
      biological functions. More than one third of these fragments were identified by
      multiple peptide sequences, and more than one half of the identified species were
      in vivo cleavage products of parent proteins. An estimated 700 serum peptides or
      proteins were predicted that had not been reported in previous serum databases.
      Several proteolytic fragments of larger molecules that may be cancer-related were
      confirmed immunologically in blood by Western blotting and peptide
      immunocompetition. BRCA2, a 390-kDa low-abundance nuclear protein linked to
      cancer susceptibility, was represented in sera as a series of specific fragments
      bound to albumin. CONCLUSION: Carrier-protein harvesting provides a rich source
      of candidate peptides and proteins with potential diverse tissue and cellular
      origins that may reflect important disease-related information.

PMID- 16099938
TI  - Drug testing in blood: validated negative-ion chemical ionization gas
      chromatographic-mass spectrometric assay for enantioselective measurement of the
      designer drugs MDEA, MDMA, and MDA and its application to samples from a
      controlled study with MDMA.
AB  - BACKGROUND: The enantiomers of the designer drugs 3,4-methylenedioxyamphetamine
      (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4
      methylenedioxyethylamphetamine (MDEA) differ in their pharmacologic and
      toxicologic potency. The aim of this study was to develop an assay for measuring
      these enantiomers in small plasma volumes and to analyze samples from a
      controlled study with MDMA. METHODS: The analytes were extracted from < or = 0.2
      mL of plasma by mixed-mode solid-phase extraction. After derivatization with S-(
      )-heptafluorobutyrylprolyl chloride, the resulting diastereomers were separated
      by gas chromatography (HP-5MS) within 17 min and detected by mass spectrometry in
      the negative-ion chemical ionization mode. The method was fully validated and
      applied to samples from a controlled study in which a single dose of racemic MDMA
      (75 mg) was administered. RESULTS: The derivatized enantiomers were well
      separated and detected with good sensitivity. The assay was linear (per
      enantiomer) at 1-50 microg/L for MDA and 5-250 microg/L for MDMA and MDEA.
      Analytical recovery, accuracy, repeatability, and intermediate precision data
      were within required limits. Extraction yields were 82.1%-95.3%. In the study
      samples, concentrations of R-(-)-MDMA significantly exceeded those of S-(+)-MDMA.
      Their ratios (R vs S) were always >1.0 and increased over time. Concentrations of
      S-(+)-MDA exceeded those of R-(-)-MDA, their ratios (R vs S) also increasing over
      time but remaining <1.0. CONCLUSIONS: This assay enables sensitive, reliable, and
      fast enantioselective measurement of MDA, MDMA, and MDEA in small volumes of
      plasma. The controlled study data confirm previous findings of MDMA and MDA
      enantiomer ratios (R vs S) increasing over time after ingestion of racemic MDMA.

PMID- 16099939
TI  - Multiplex human papillomavirus serology based on in situ-purified glutathione s
      transferase fusion proteins.
AB  - BACKGROUND: More than 100 different human papillomaviruses (HPVs) can cause
      proliferative diseases, many of which are malignant, such as cervical cancer. HPV
      serology is complex because infection and disease lead to distinct type-specific
      antibody responses. Using bead-based technology, we have developed an assay
      platform that allows the simultaneous detection of antibodies against up to 100
      in situ affinity-purified recombinant HPV proteins. METHODS: Twenty-seven HPV
      proteins were expressed as glutathione S-transferase fusion proteins and affinity
      purified in one step by incubation of glutathione-displaying beads in bacterial
      lysate. Spectrally distinct bead sets, each carrying one particular antigen, were
      mixed, incubated with serum, and differentiated in a flow cytometer-like analyzer
      (xMAP; Luminex Corp). Antibodies bound to the antigens were detected via
      fluorescent secondary reagents. We studied 756 sera from 2 case-control studies
      of cervical cancer. RESULTS: Glutathione S-transferase fusion proteins bound with
      high affinity to glutathione-displaying beads (Kd = 6.9 x 10(-9) mol/L). The
      dynamic range of multiplex serology covered 1.5 orders of magnitude, and
      antibodies were detected at serum dilutions >1:1,000,000. Imprecision (median CV)
      was < or = 5.4%, and assay reproducibility was high (R2 = 0.97). Results on
      clinical samples showed high concordance with ELISA (kappa = 0.846), but
      multiplex serology exhibited increased detection of weak antibody responses.
      Antibodies to the E6 oncoproteins of the rare HPV types 52 and 58 were associated
      with cervical cancer (P < 0.001). CONCLUSION: Multiplex serology enables antibody
      analyses of large numbers of sera against up to 100 antigens in parallel and has
      the potential to replace ELISA technology.

PMID- 16099940
TI  - Real-time PCR assays targeting a unique chromosomal sequence of Yersinia pestis.
AB  - BACKGROUND: Yersinia pestis, the causative agent of the zoonotic infection
      plague, is a major concern as a potential bioweapon. Current real-time PCR assays
      used for Y. pestis detection are based on plasmid targets, some of which may
      generate false-positive results. METHODS: Using the yp48 gene of Y. pestis, we
      designed and tested 2 real-time TaqMan minor groove binder (MGB) assays that
      allowed us to use chromosomal genes as both confirmatory and differential targets
      for Y. pestis. We also designed several additional assays using both Simple-Probe
      and MGB Eclipse probe technologies for the selective differentiation of Yersinia
      pseudotuberculosis from Y. pestis. These assays were designed around a 25-bp
      insertion site recently identified within the yp48 gene of Y. pseudotuberculosis.
      RESULTS: The Y. pestis-specific assay distinguished this bacterium from other
      Yersinia species but had unacceptable low-level detection of Y.
      pseudotuberculosis, a closely related species. Simple-Probe and MGB Eclipse
      probes specific for the 25-bp insertion detected only Y. pseudotuberculosis DNA.
      Probes that spanned the deletion site detected both Y. pestis and Y.
      pseudotuberculosis DNA, and the 2 species were clearly differentiated by a post
      PCR melting temperature (Tm) analysis. The Simple-Probe assay produced an almost
      7 degrees C Tm difference and the MGB Eclipse probe a slightly more than 4
      degrees C difference. CONCLUSIONS: Our method clearly discriminates Y. pestis DNA
      from all other Yersinia species tested and from the closely related Y.
      pseudotuberculosis. These chromosomal assays are important both to verify the
      presence of Y. pestis based on a chromosomal target and to easily distinguish it
      from Y. pseudotuberculosis.

PMID- 16099941
TI  - Measurement of midregional proadrenomedullin in plasma with an immunoluminometric
      assay.
AB  - BACKGROUND: Adrenomedullin (ADM) is a potent vasodilatory peptide, and
      circulating concentrations have been described for several disease states,
      including dysfunction of the cardiovascular system and sepsis. Reliable
      quantification has been hampered by the short half-life, the existence of a
      binding protein, and physical properties. Here we report the technical evaluation
      of an assay for midregional pro-ADM (MR-proADM) that does not have these
      problems. METHODS: MR-proADM was measured in a sandwich immunoluminometric assay
      using 2 polyclonal antibodies to amino acids 45-92 of proADM. The reference
      interval was defined in EDTA plasma of 264 healthy individuals (117 male, 147
      female), and increased MR-proADM concentrations were found in 95 patients with
      sepsis and 54 patients with cardiovascular disease. RESULTS: The assay has an
      analytical detection limit of 0.08 nmol/L, and the interassay CV was <20% for
      values >0.12 nmol/L. The assay was linear on dilution with undisturbed recovery
      of the analyte. EDTA-, heparin-, and citrate-plasma samples were stable (<20%
      loss of analyte) for at least 3 days at room temperature, 14 days at 4 degrees C,
      and 1 year at -20 degrees C. MR-proADM values followed a gaussian distribution in
      healthy individuals with a mean (SD) of 0.33 (0.07) nmol/L (range, 0.10-0.64
      nmol/L), without significant difference between males or females. The correlation
      coefficient for MR-proADM vs age was 0.50 (P < 0.001). MR-proADM was
      significantly (P < 0.001) increased in patients with cardiovascular disease
      [median (range), 0.56 (0.08-3.9) nmol/L] and patients with sepsis [3.7 (0.72
      25.4) nmol/L]. CONCLUSIONS: MR-proADM is stable in plasma of healthy individuals
      and patients. MR-proADM measurements may be useful for evaluating patients with
      sepsis, systemic inflammation, or heart failure.

PMID- 16099942
TI  - Use of proteomic methods to identify serum biomarkers associated with rat liver
      toxicity or hypertrophy.
AB  - BACKGROUND: Our objectives were to identify serum marker proteins in rats that
      might serve as sensitive indicators of hepatomegaly, hepatocellular necrosis, or
      hepatobiliary injury and to use them to analyze data from a collaborative
      proteomics project. METHODS: In each of 4 studies comprising the collaborative
      project, rats were given 1 of 4 compounds that target the liver through different
      mechanisms. Sera and liver samples were collected by terminal bleeds at 1 of 3
      postdose time points. Sera were depleted of major secretory proteins and then
      separated into protein features by 2-dimensional gel electrophoresis (2DGE).
      Liver specimens were also processed and subjected to 2DGE. Protein spots that
      significantly increased or decreased in quantity after drug treatment were
      recovered, digested, analyzed by mass spectroscopy, and compared with available
      databases for identification. Criteria for further consideration were (a)
      temporal expression (i.e., increase or decrease at early, fulminant, or recovery
      periods), (b) known biological function, (c) probable hepatic origin, and (d) any
      previous association with toxicity in published studies. Markers that changed
      significantly at the early time point were important because of their potential
      sensitivity for signaling minimal damage. RESULTS: Vitamin D-binding protein,
      paraoxonase, cellular retinol-binding protein, malate dehydrogenase, F-protein,
      and purine nucleoside phosphorylase were identified as empirically confirmed
      serum markers for hepatic effects in drug-treated rats. CONCLUSION: Proteomics
      can be applied for the identification and confirmation of peripheral biomarkers
      for altered liver function after toxicant exposure.

PMID- 16099943
TI  - Post-embryonic ablation of AgRP neurons in mice leads to a lean, hypophagic
      phenotype.
AB  - Agouti-related protein (AgRP) and neuropeptide Y (NPY) are colocalized in arcuate
      nucleus (arcuate) neurons implicated in the regulation of energy balance. Both
      AgRP and NPY stimulate food intake when administered into the third ventricle and
      are up-regulated in states of negative energy balance. However, mice with
      targeted deletion of either NPY or AgRP or both do not have major alterations in
      energy homeostasis. Using bacterial artificial chromosome (BAC) transgenesis we
      have targeted expression of a neurotoxic CAG expanded form of ataxin-3 to AgRP
      expressing neurons in the arcuate. This resulted in a 47% loss of AgRP neurons by
      16 weeks of age, a significantly reduced body weight, (wild-type mice (WT) 34.7+/
      0.7 g vs. transgenic mice (Tg) 28.6+/-0.6 g, P<0.001), and reduced food intake
      (WT 5.0+/-0.2 vs. Tg 3.6+/-0.1 g per day, P<0.001). Transgenic mice had
      significantly reduced total body fat, plasma insulin, and increased brown adipose
      tissue UCP1 expression. Transgenic mice failed to respond to peripherally
      administered ghrelin but retained sensitivity to PYY 3-36. These data suggest
      that postembryonic partial loss of AgRP/NPY neurons leads to a lean, hypophagic
      phenotype.

PMID- 16099944
TI  - T-cadherin protects endothelial cells from oxidative stress-induced apoptosis.
AB  - In vascular tissue, T-cadherin (T-cad) is up-regulated in vivo under disease
      conditions associated with oxidative stress and concomitant cell migration,
      proliferation and apoptosis/survival. Using cultures of human umbilical vein
      endothelial cells (HUVEC), we examined whether there is a functional relationship
      between oxidative stress, T-cad expression, and cell survival status. Culture of
      HUVEC under conditions of oxidative stress (e.g., serum deprivation, inclusion of
      H2O2) resulted in increased T-cad expression. Oxidative stress-induced increases
      in T-cad were inhibited by the free radical-scavenging antioxidant, N
      acetylcysteine, and the flavin-containing oxidase inhibitor, diphenyleneiodonium.
      Thus reactive oxygen species (ROS) contribute to stress-induced elevation of T
      cad in HUVEC. Compared with control cells, HUVEC overexpressing T-cad (T-cad+
      HUVEC) had higher phosphorylation levels for phosphatidylinositol 3-kinase (PI3K)
      target Akt and mTOR target p70(S6K) (survival pathway regulators), but lower
      levels for p38MAPK (death pathway regulator). T-cad+-HUVEC exposed to stress
      (serum-deprivation, TNF-alpha, actinomycin D, staurosporine) exhibited reduced
      caspase activation together with increased cell survival. Protection against
      stress-induced apoptosis in T-cad+-HUVEC was abrogated by either PI3K-inhibitor
      wortmannin or mTOR-inhibitor rapamycin. We conclude that T-cad overexpression in
      HUVEC protects against stress-induced apoptosis through activation of the
      PI3K/Akt/mTOR survival signal pathway and concomitant suppression of the p38 MAPK
      proapoptotic pathway. ROS-induced changes in T-cad expression may play an
      important role in controlling tissue cellularity during vascular remodeling.

PMID- 16099945
TI  - Molecular composition of drusen and possible involvement of anti-retinal
      autoimmunity in two different forms of macular degeneration in cynomolgus monkey
      (Macaca fascicularis).
AB  - We have previously reported a cynomolgus monkey (Macaca fascicularis) pedigree
      with early onset macular degeneration that develops drusen at 2 yr after birth.
      In this study, the molecular composition of drusen in monkeys affected with late
      onset and early onset macular degeneration was both characterized. Involvement of
      anti-retinalautoimmunity in the deposition of drusen and the pathogenesis of the
      disease was also evaluated. Funduscopic and histological examinations were
      performed on 278 adult monkeys (mean age=16.94 yr) for late onset macular
      degeneration. The molecular composition of drusen was analyzed by
      immunohistochemistry and/or direct proteome analysis using liquid chromatography
      tandem mass spectroscopy (LC-MS/MS). Anti-retinal autoantibodies in sera were
      screened in 20 affected and 10 age-matched control monkeys by Western blot
      techniques. Immunogenic molecules were identified by 2D electrophoresis and LC
      MS/MS. Relative antibody titer against each antigen was determined by ELISA in
      sera from 42 affected (late onset) and 41 normal monkeys. Yellowish-white spots
      in the macular region were observed in 90 (32%) of the late onset monkeys that
      were examined. Histological examination demonstrated that drusen or degenerative
      retinal pigment epithelium (RPE) cells were associated with the pigmentary
      abnormalities. Drusen in both late and early onset monkeys showed
      immunoreactivities for apolipoprotein E, amyloid P component, complement
      component C5, the terminal C5b-9 complement complex, vitronectin, and membrane
      cofactor protein. LC-MS/MS analyses identified 60 proteins as constituents of
      drusen, including a number of common components in drusen of human age-related
      macular degeneration (AMD), such as annexins, crystallins, immunoglobulins, and
      complement components. Half of the affected monkeys had single or multiple
      autoantibodies against 38, 40, 50, and 60 kDa retinal proteins. The reacting
      antigens of 38 and 40 kDa were identified as annexin II and mu-crystallin,
      respectively. Relative antibody titer against annexin II in affected monkeys was
      significantly higher than control animals (P<0.01). Significant difference was
      not observed in antibody titer against mu-crystallin; however, several affected
      monkeys showed considerably elevated titer (360-610%) compared with the mean for
      unaffected animals. Monkey drusen both in late and early onset forms of macular
      degeneration had common components with drusen in human AMD patients, indicating
      that chronic inflammation mediated by complement activation might also be
      involved in the formation of drusen in these affected monkeys. The high
      prevalence of anti-retinalautoantibodies in sera from affected monkeys
      demonstrated an autoimmune aspect of the pathogenesis of the disease. Although
      further analyses are required to determine whether and how autoantibodies against
      annexin II or mu-crystallin relate to the pathogenesis of the disease, it could
      be hypothesized that immune responses directed against these antigens might
      trigger chronic activation of the complement cascade at the site of drusen
      formation.

PMID- 16099946
TI  - The C. elegans ortholog of mammalian Ku70, interacts with insulin-like signaling
      to modulate stress resistance and life span.
AB  - The mammalian Ku heterodimer has important roles in DNA double strand break
      repair, telomere maintenance, cell cycle checkpoint-arrest, tumor suppression,
      and cellular stress resistance. To investigate the evolutionarily conserved
      functions of Ku, we knocked down expression by RNA interference (RNAi) of Ku
      genes in C. elegans. We found that C. elegans Ku70 (CKU-70) is required for
      resistance to genotoxic stress, regulates cytotoxic stress responses, and
      influences aging. The latter effects are dependent on an IGF-1/insulin-like
      signaling pathway previously shown to affect life span. Reduction of CKU-70
      activity amplifies the aging phenotype of long-lived insulin receptor daf-2
      mutations in a daf-16-dependent manner. These observations support the view that
      organismal stress resistance determines life span and Ku70 modulates these
      effects.

PMID- 16099947
TI  - Selectivity of the ubiquitin pathway for oxidatively modified proteins: relevance
      to protein precipitation diseases.
AB  - There is now consensus that the accumulation of oxidatively modified proteins is
      cytotoxic and causally related to several age-related diseases, including the
      amyloid diseases and age-related cataracts. There is also general agreement that
      proteolytic pathways provide a quality control mechanism to limit accumulation of
      damaged proteins. Although many researchers assume that the ubiquitin pathway is
      involved in recognition and proteolytic removal of oxidatively modified proteins,
      which are produced upon cellular stress, there has been no direct evidence to
      support this hypothesis. In this work, we used a novel proteolysis-resistant
      ubiquitin variant to demonstrate that ubiquitin conjugates isolated from
      oxidatively stressed mammalian cells are enriched 3.3-15-fold for oxidatively
      modified proteins and that failure to execute ubiquitin-dependent proteolysis
      renders various cell types more susceptible to oxidative stress-related
      cytotoxicity. These results were corroborated using several inhibitors of the
      ubiquitin proteasome pathway, including PS-341, an anticancer drug in clinical
      use. Taken together the data indicate that the ubiquitin proteolytic pathway
      recognizes and removes oxidatively modified proteins, and that failure of this
      system, as occurs upon aging or stress, may be involved in and exacerbate
      cytotoxicity and age-related syndromes in which accumulation of ubiquitinated and
      oxidatively modified proteins has an etiologic role.

PMID- 16099948
TI  - Erythropoietin is neuroprotective, improves functional recovery, and reduces
      neuronal apoptosis and inflammation in a rodent model of experimental closed head
      injury.
AB  - Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in
      young people in industrialized countries. Although various anti-inflammatory and
      antiapoptotic modalities have shown neuroprotective effects in experimental
      models of TBI, to date, no specific pharmacological agent aimed at blocking the
      progression of secondary brain damage has been approved for clinical use.
      Erythropoietin (Epo) belongs to the cytokine superfamily and has traditionally
      been viewed as a hematopoiesis-regulating hormone. The newly discovered
      neuroprotective properties of Epo lead us to investigate its effect in TBI in a
      mouse model of closed head injury. Recombinant human erythropoietin (rhEpo) was
      injected at 1 and 24 h after TBI, and the effect on recovery of motor and
      cognitive functions, tissue inflammation, axonal degeneration, and apoptosis was
      evaluated up to 14 days. Motor deficits were lower, cognitive function was
      restored faster, and less apoptotic neurons and caspase-3 expression were found
      in rhEpo-treated as compared with vehicle-treated animals (P<0.05). Axons at the
      trauma area in rhEpo-treated mice were relatively well preserved compared with
      controls (shown by their density; P<0.01). Immunohistochemical analysis revealed
      a reduced activation of glial cells by staining for GFAP and complement receptor
      type 3 (CD11b/CD18) in the injured hemisphere of Epo- vs. vehicle-treated
      animals. We propose that further studies on Epo in TBI should be conducted in
      order to consider it as a novel therapy for TBI.

PMID- 16099949
TI  - The mRNA of the Arabidopsis gene FT moves from leaf to shoot apex and induces
      flowering.
AB  - Day length controls flowering time in many plants. The day-length signal is
      perceived in the leaf, but how this signal is transduced to the shoot apex, where
      floral initiation occurs, is not known. In Arabidopsis, the day-length response
      depends on the induction of the FLOWERING LOCUS T (FT) gene. We show here that
      local induction of FT in a single Arabidopsis leaf is sufficient to trigger
      flowering. The FT messenger RNA is transported to the shoot apex, where
      downstream genes are activated. These data suggest that the FT mRNA is an
      important component of the elusive "florigen" signal that moves from leaf to
      shoot apex.

PMID- 16099950
TI  - Radiosonde daytime biases and late-20th century warming.
AB  - The temperature difference between adjacent 0000 and 1200 UTC weather balloon
      (radiosonde) reports shows a pervasive tendency toward cooler daytime compared to
      nighttime observations since the 1970s, especially at tropical stations. Several
      characteristics of this trend indicate that it is an artifact of systematic
      reductions over time in the uncorrected error due to daytime solar heating of the
      instrument and should be absent from accurate climate records. Although other
      problems may exist, this effect alone is of sufficient magnitude to reconcile
      radiosonde tropospheric temperature trends and surface trends during the late
      20th century.

PMID- 16099951
TI  - Amplification of surface temperature trends and variability in the tropical
      atmosphere.
AB  - The month-to-month variability of tropical temperatures is larger in the
      troposphere than at Earth's surface. This amplification behavior is similar in a
      range of observations and climate model simulations and is consistent with basic
      theory. On multidecadal time scales, tropospheric amplification of surface
      warming is a robust feature of model simulations, but it occurs in only one
      observational data set. Other observations show weak, or even negative,
      amplification. These results suggest either that different physical mechanisms
      control amplification processes on monthly and decadal time scales, and models
      fail to capture such behavior; or (more plausibly) that residual errors in
      several observational data sets used here affect their representation of long
      term trends.

PMID- 16099952
TI  - Heading off an influenza pandemic.

PMID- 16099953
TI  - Evolution. Vatican astronomer rebuts cardinal's attack on Darwinism.

PMID- 16099954
TI  - Avian influenza. 'Pandemic vaccine' appears to protect only at high doses.

PMID- 16099955
TI  - Genomics. Painstaking approach pays off for rice sequencing project.

PMID- 16099956
TI  - HIV/AIDS. Report of novel treatment aimed at latent HIV raises the 'c word'.

PMID- 16099957
TI  - Biotechnology. Calming fears, no foreign genes found in Mexico's maize.

PMID- 16099958
TI  - Physics. Physicists get the dope on disorder in high-temperature superconductors.

PMID- 16099960
TI  - HIV/AIDS. Hedged bet: an unusual AIDS vaccine trial.

PMID- 16099959
TI  - HIV/AIDS. Prevention cocktails: combining tools to Stop HIV's spread.

PMID- 16099961
TI  - Ecology. Beloved Arctic station braces for its own climate change.

PMID- 16099962
TI  - Archaeology. Unraveling khipu's secrets.

PMID- 16099963
TI  - Using ethics to fight bioterrorism.

PMID- 16099964
TI  - Madrid center not quite in limbo.

PMID- 16099965
TI  - Comment on "Molybdenum isotope evidence for widespread anoxia in mid-Proterozoic
      oceans".

PMID- 16099966
TI  - Security. Microchallenges of chemical weapons proliferation.

PMID- 16099967
TI  - Cosmology. Anthropic reasoning.

PMID- 16099968
TI  - Plant science. The right time and place for making flowers.

PMID- 16099969
TI  - Geochemistry. Biogeochemical cycling of iron isotopes.

PMID- 16099970
TI  - Structural biology. Choosing the crystallization path less traveled.

PMID- 16099972
TI  - The tsunami's psychological aftermath.

PMID- 16099973
TI  - Toward inherently secure and resilient societies.
AB  - Recent years have seen a number of challenges to social stability and order,
      ranging from terrorist attacks and natural disasters to epidemics such as AIDS
      and SARS. Such challenges have generated specific policy responses, such as
      enhanced security at transportation hubs and planned deployment of a global
      tsunami detection network. However, the range of challenges and the practical
      impossibility of adequately addressing each in turn argue for adoption of a more
      comprehensive systems perspective. This should be based on the principle of
      enhancing social and economic resiliency as well as meeting security and
      emergency response needs and, to the extent possible, developing and implementing
      dual-use technologies that offer societal benefits even if anticipated disasters
      never occur.

PMID- 16099974
TI  - Social-ecological resilience to coastal disasters.
AB  - Social and ecological vulnerability to disasters and outcomes of any particular
      extreme event are influenced by buildup or erosion of resilience both before and
      after disasters occur. Resilient social-ecological systems incorporate diverse
      mechanisms for living with, and learning from, change and unexpected shocks.
      Disaster management requires multilevel governance systems that can enhance the
      capacity to cope with uncertainty and surprise by mobilizing diverse sources of
      resilience.

PMID- 16099975
TI  - Insurance in a climate of change.
AB  - Catastrophe insurance provides peace of mind and financial security. Climate
      change can have adverse impacts on insurance affordability and availability,
      potentially slowing the growth of the industry and shifting more of the burden to
      governments and individuals. Most forms of insurance are vulnerable, including
      property, liability, health, and life. It is incumbent on insurers, their
      regulators, and the policy community to develop a better grasp of the physical
      and business risks. Insurers are well positioned to participate in public-private
      initiatives to monitor loss trends, improve catastrophe modeling, address the
      causes of climate change, and prepare for and adapt to the impacts.

PMID- 16099976
TI  - Refocusing disaster aid.
AB  - With new modeling techniques for estimating and pricing the risks of natural
      disasters, the donor community is now in a position to help the poor cope with
      the economic repercussions of disasters by assisting before they happen. Such
      assistance is possible with the advent of novel insurance instruments for
      transferring catastrophe risks to the global financial markets. Donor-supported
      risk-transfer programs not only would leverage limited disaster-aid budgets but
      also would free recipient countries from depending on the vagaries of
      postdisaster assistance. Both donors and recipients stand to gain, especially
      because the instruments can be closely coupled with preventive measures.

PMID- 16099977
TI  - Soil invertebrates disrupt carbon flow through fungal networks.
AB  - Annual carbon flux through soil respiration is ten times greater than fossil fuel
      combustion, but its component parts are poorly understood because they are the
      product of complex multitrophic interactions between soil organisms. A major
      component of carbon flux from plants to soil occurs through networks of symbiotic
      arbuscular mycorrhizal fungi. Here, using 13CO2 pulse labeling, we show that
      natural densities of the numerically dominant fungal feeding invertebrate
      Protaphorura armata (order Collembola) reduces 13C enrichment of mycorrhizosphere
      respiration by 32%. Our findings emphasize the importance of multitrophic
      interactions in regulating respiration of recent plant photosynthate from soil.

PMID- 16099978
TI  - Atomic-Scale Sources and Mechanism of Nanoscale Electronic Disorder in
      Bi2Sr2CaCu2O8+delta.
AB  - The randomness of dopant atom distributions in cuprate high-critical temperature
      superconductors has long been suspected to cause nanoscale electronic disorder.
      In the superconductor Bi2Sr2CaCu2O8+delta, we identified populations of atomic
      scale impurity states whose spatial densities follow closely those of the oxygen
      dopant atoms. We found that the impurity-state locations are strongly correlated
      with all manifestations of the nanoscale electronic disorder. This disorder
      occurs via an unanticipated mechanism exhibiting high-energy spectral weight
      shifts, with associated strong superconducting coherence peak suppression but
      very weak scattering of low-energy quasi-particles.

PMID- 16099979
TI  - FD, a bZIP protein mediating signals from the floral pathway integrator FT at the
      shoot apex.
AB  - FLOWERING LOCUS T (FT) is a conserved promoter of flowering that acts downstream
      of various regulatory pathways, including one that mediates photoperiodic
      induction through CONSTANS (CO), and is expressed in the vasculature of
      cotyledons and leaves. A bZIP transcription factor, FD, preferentially expressed
      in the shoot apex is required for FT to promote flowering. FD and FT are
      interdependent partners through protein interaction and act at the shoot apex to
      promote floral transition and to initiate floral development through
      transcriptional activation of a floral meristem identity gene, APETALA1 (AP1). FT
      may represent a long-distance signal in flowering.

PMID- 16099980
TI  - Integration of spatial and temporal information during floral induction in
      Arabidopsis.
AB  - Flowering of Arabidopsis is regulated by several environmental and endogenous
      signals. An important integrator of these inputs is the FLOWERING LOCUS T (FT)
      gene, which encodes a small, possibly mobile protein. A primary response to
      floral induction is the activation of FT RNA expression in leaves. Because
      flowers form at a distant site, the shoot apex, these data suggest that FT
      primarily controls the timing of flowering. Integration of temporal and spatial
      information is mediated in part by the bZIP transcription factor FD, which is
      already expressed at the shoot apex before floral induction. A complex of FT and
      FD proteins in turn can activate floral identity genes such as APETALA1 (AP1).

PMID- 16099981
TI  - Origin of brittle cleavage in iridium.
AB  - Iridium is unique among the face-centered cubic metals in that it undergoes
      brittle cleavage after a period of plastic deformation under tensile stress.
      Atomistic simulation using a quantum-mechanically derived bond-order potential
      shows that in iridium, two core structures for the screw dislocation are
      possible: a glissile planar core and a metastable nonplanar core. Transformation
      between the two core structures is athermal and leads to exceptionally high rates
      of cross slip during plastic deformation. Associated with this athermal cross
      slip is an exponential increase in the dislocation density and strong work
      hardening from which brittle cleavage is a natural consequence.

PMID- 16099982
TI  - Photochemical mass-independent sulfur isotopes in achondritic meteorites.
AB  - Sulfides from four achondrite meteorite groups are enriched in 33S (up to 0.040
      per mil) as compared with primitive chondrites and terrestrial standards. Stellar
      nucleosynthesis and cosmic ray spallation are ruled out as causes of the anomaly,
      but photochemical reactions in the early solar nebula could produce the isotopic
      composition. The large 33S excess present in oldhamite from the Norton County
      aubrite (0.161 per mil) suggests that refractory sulfide minerals condensed from
      a nebular gas with an enhanced carbon-oxygen ratio, but otherwise solar
      composition is the carrier. The presence of a mass-independent sulfur effect in
      meteorites argues for a similar process that could account for oxygen isotopic
      anomalies observed in refractory inclusions in primitive chondrites.

PMID- 16099983
TI  - Khipu accounting in ancient Peru.
AB  - Khipu are knotted-string devices that were used for bureaucratic recording and
      communication in the Inka Empire. We recently undertook a computer analysis of 21
      khipu from the Inka administrative center of Puruchuco, on the central coast of
      Peru. Results indicate that this khipu archive exemplifies the way in which
      census and tribute data were synthesized, manipulated, and transferred between
      different accounting levels in the Inka administrative system.

PMID- 16099984
TI  - Nature of phosphorus limitation in the ultraoligotrophic eastern Mediterranean.
AB  - Phosphate addition to surface waters of the ultraoligotrophic, phosphorus-starved
      eastern Mediterranean in a Lagrangian experiment caused unexpected ecosystem
      responses. The system exhibited a decline in chlorophyll and an increase in
      bacterial production and copepod egg abundance. Although nitrogen and phosphorus
      colimitation hindered phytoplankton growth, phosphorous may have been transferred
      through the microbial food web to copepods via two, not mutually exclusive,
      pathways: (i) bypass of the phytoplankton compartment by phosphorus uptake in
      heterotrophic bacteria and (ii) tunnelling, whereby phosphate luxury consumption
      rapidly shifts the stoichiometric composition of copepod prey. Copepods may thus
      be coupled to lower trophic levels through interactions not usually considered.

PMID- 16099985
TI  - Direct control of germline stem cell division and cyst growth by neural insulin
      in Drosophila.
AB  - Stem cells reside in specialized niches that provide signals required for their
      maintenance and division. Tissue-extrinsic signals can also modify stem cell
      activity, although this is poorly understood. Here, we report that neural-derived
      Drosophila insulin-like peptides (DILPs) directly regulate germline stem cell
      division rate, demonstrating that signals mediating the ovarian response to
      nutritional input can modify stem cell activity in a niche-independent manner. We
      also reveal a crucial direct role of DILPs in controlling germline cyst growth
      and vitellogenesis.

PMID- 16099986
TI  - TAZ, a transcriptional modulator of mesenchymal stem cell differentiation.
AB  - Mesenchymal stem cells (MSCs) are a pluripotent cell type that can differentiate
      into several distinct lineages. Two key transcription factors, Runx2 and
      peroxisome proliferator-activated receptor gamma (PPARgamma), drive MSCs to
      differentiate into either osteoblasts or adipocytes, respectively. How these two
      transcription factors are regulated in order to specify these alternate cell
      fates remains a pivotal question. Here we report that a 14-3-3-binding protein,
      TAZ (transcriptional coactivator with PDZ-binding motif), coactivates Runx2
      dependent gene transcription while repressing PPARgamma-dependent gene
      transcription. By modulating TAZ expression in model cell lines, mouse embryonic
      fibroblasts, and primary MSCs in culture and in zebrafish in vivo, we observed
      alterations in osteogenic versus adipogenic potential. These results indicate
      that TAZ functions as a molecular rheostat that modulates MSC differentiation.

PMID- 16099987
TI  - Formation of regulatory patterns during signal propagation in a Mammalian
      cellular network.
AB  - We developed a model of 545 components (nodes) and 1259 interactions representing
      signaling pathways and cellular machines in the hippocampal CA1 neuron. Using
      graph theory methods, we analyzed ligand-induced signal flow through the system.
      Specification of input and output nodes allowed us to identify functional
      modules. Networking resulted in the emergence of regulatory motifs, such as
      positive and negative feedback and feedforward loops, that process information.
      Key regulators of plasticity were highly connected nodes required for the
      formation of regulatory motifs, indicating the potential importance of such
      motifs in determining cellular choices between homeostasis and plasticity.

PMID- 16099988
TI  - In situ stable isotope probing of methanogenic archaea in the rice rhizosphere.
AB  - Microorganisms living in anoxic rice soils contribute 10 to 25% of global methane
      emissions. The most important carbon source for CH4 production is plant-derived
      carbon that enters soil as root exudates and debris. Pulse labeling of rice
      plants with 13CO2 resulted in incorporation of 13C into the ribosomal RNA of Rice
      Cluster I Archaea in the soil, indicating that this archaeal group plays a key
      role in CH4 production from plant-derived carbon. This group of microorganisms
      has not yet been isolated but appears to be of global environmental importance.

PMID- 16099989
TI  - Complete genome sequence and lytic phase transcription profile of a
      Coccolithovirus.
AB  - The genus Coccolithovirus is a recently discovered group of viruses that infect
      the globally important marine calcifying microalga Emiliania huxleyi. Among the
      472 predicted genes of the 407,339-base pair genome are a variety of unexpected
      genes, most notably those involved in biosynthesis of ceramide, a sphingolipid
      known to induce apoptosis. Uniquely for algal viruses, it also contains six RNA
      polymerase subunits and a novel promoter, suggesting this virus encodes its own
      transcription machinery. Microarray transcriptomic analysis reveals that 65% of
      the predicted virus-encoded genes are expressed during lytic infection of E.
      huxleyi.

PMID- 16099990
TI  - Structural basis for the activation of cholera toxin by human ARF6-GTP.
AB  - The Vibrio cholerae bacterium causes devastating diarrhea when it infects the
      human intestine. The key event is adenosine diphosphate (ADP)-ribosylation of the
      human signaling protein GSalpha, catalyzed by the cholera toxin A1 subunit
      (CTA1). This reaction is allosterically activated by human ADP-ribosylation
      factors (ARFs), a family of essential and ubiquitous G proteins. Crystal
      structures of a CTA1:ARF6-GTP (guanosine triphosphate) complex reveal that
      binding of the human activator elicits dramatic changes in CTA1 loop regions that
      allow nicotinamide adenine dinucleotide (NAD+) to bind to the active site. The
      extensive toxin:ARF-GTP interface surface mimics ARF-GTP recognition of normal
      cellular protein partners, which suggests that the toxin has evolved to exploit
      promiscuous binding properties of ARFs.

PMID- 16099991
TI  - Pre-unfolding resonant oscillations of single green fluorescent protein
      molecules.
AB  - Fluorescence spectroscopy of a green fluorescent protein mutant at single
      molecule resolution has revealed a remarkable oscillatory behavior that can also
      be driven by applied fields. We show that immediately before unfolding, several
      periodic oscillations among the chemical substates of the protein chromophore
      occur. We also show that applied alternating electric or acoustic fields, when
      tuned to the protein characteristic frequencies, give rise to strong resonance
      effects.

PMID- 16099992
TI  - NPC1 gene deficiency leads to lack of neural stem cell self-renewal and abnormal
      differentiation through activation of p38 mitogen-activated protein kinase
      signaling.
AB  - Neural stem cells (NSCs) are capable of giving rise to neurons, glia, and
      astrocytes. Although self-renewal and differentiation in NSCs are regulated by
      many genes, such as Notch and Numb, little is known about the role of defective
      genes on the self-renewal and differentiation of NSCs from developing brain. The
      Niemann-Pick type C1 (NPC1) disease is a neurodegenerative disease caused by a
      mutation of the NPC1 gene that affects the function of the NPC1 protein. The
      ability of NSC self-renewal and differentiation was investigated using a model of
      NPC1 disease. The NPC1 disorder significantly affected the self-renewal ability
      of NSCs, as well as the differentiation. NSCs from NPC1-/- mice showed impaired
      self-renewal ability compared with the NPC1+/+ mice. These alterations were
      accompanied by the enhanced activity of p38 mitogen-activated protein kinases
      (MAPKs). Further, the specific p38 MAPK inhibitor SB202190 improved the self
      renewal ability of NSCs from NPC-/- mice. This indicated that the NPC1 deficiency
      can lead to lack of self-renewal and altered differentiation of NSCs mediated by
      the activation of p38 MAPK, impairing the generation of neurospheres from NPC1-/-
      Thus, the NPC1 gene may play a crucial role in NSC self-renewal associated with
      p38 MAPK.

PMID- 16099993
TI  - Nucleofection is an efficient nonviral transfection technique for human bone
      marrow-derived mesenchymal stem cells.
AB  - Viral-based techniques are the most efficient systems to deliver DNA into stem
      cells because they show high gene transduction and transgene expression in many
      cellular models. However, the use of viral vectors has several disadvantages
      mainly involving safety risks. Conversely, nonviral methods are rather
      inefficient for most primary cells. The Nucleofector technology, a new nonviral
      electroporation-based gene transfer technique, has proved to be an efficient tool
      for transfecting hard-to-transfect cell lines and primary cells. However, little
      is known about the capacity of this technique to transfect adult stem cells. In
      this study, we applied the Nucleofector technology to engineer human bone marrow-
      derived mesenchymal stem cells (hMSCs). Using a green fluorescent protein
      reporter vector, we demonstrated a high transgene expression level using U-23 and
      C-17 pulsing programs: 73.7%+/-2.9% and 42.5%+/-3.4%, respectively. Cell
      recoveries and viabilities were 38.7%+/-2.9%, 44.5%+/-3.9% and 91.4%+/-1.3%,
      94.31%+/-0.9% for U-23 and C-17, respectively. Overall, the transfection
      efficiencies were 27.4%+/-2.9% (U-23) and 16.6%+/-1.4% (C-17) compared with
      3.6%+/-2.4% and 5.4%+/-3.4% of other nonviral transfection systems, such as
      FUGENE6 and DOTAP, respectively (p<.005 for all comparisons). Nucleofection did
      not affect the immunophenotype of hM-SCs, their normal differentiation potential,
      or ability to inhibit T-cell alloreactivity. Moreover, the interleukin-12 gene
      could be successfully transfected into hMSCs, and the immunomodulatory cytokine
      was produced in great amount for at least 3 weeks without impairment of its
      biological activity. In conclusion, nucleofection is an efficient nonviral
      transfection technique for hMSCs, which then may be used as cellular vehicles for
      the delivery of biological agents.

PMID- 16099994
TI  - Microarray analysis of LIF/Stat3 transcriptional targets in embryonic stem cells.
AB  - Mouse embryonic stem (ES) cells can be propagated in vitro while retaining their
      properties of pluripotency and self-renewal under the continuous presence of
      leukemia inhibitor factor (LIF). An essential role has been attributed to
      subsequent activation of the Stat3 transcription factor in mediating LIF self
      renewal response. To date, however, downstream target genes of Stat3 in ES cells
      are still unknown. To isolate these genes, we performed a microarray-based
      kinetic comparison of LIF-stimulated (undifferentiated) ES cells versus ES cells
      induced to differentiate by shutting down Stat3 activity through either LIF
      deprivation or, more specifically, expression of a Stat3 dominant-negative
      mutant. In each case, we chose the earliest time at which ES cells lose their
      self-renewal properties, as illustrated by a decrease in the number of embryoid
      bodies and blast cell colony formation as well as germ layer marker expression.
      Comparison of the two independent approaches revealed similarly regulated genes
      that are likely to be involved in the Stat3 effects on ES cell self-renewal. For
      instance, upregulation of growth factors such as the transforming growth factor
      beta relative Lefty1 or transcriptional regulators such as Id1 and Id2 and down
      regulation of the groucho-like protein Aes1 (grg5) were found. Promoter analysis
      of the aes1 gene revealed three functional Stat3 consensus sites, as shown by
      luciferase assays. Furthermore, chromatin immunoprecipitation experiment
      demonstrated that Stat3 is recruited to the promoter of aes1 in ES cells. These
      data demonstrated that the aes1 gene is a direct transcriptional target of Stat3
      in ES cells.

PMID- 16099995
TI  - Motor neuron degeneration promotes neural progenitor cell proliferation,
      migration, and neurogenesis in the spinal cords of amyotrophic lateral sclerosis
      mice.
AB  - The organization, distribution, and function of neural progenitor cells (NPCs) in
      the adult spinal cord during motor neuron degeneration in amyotrophic lateral
      sclerosis (ALS) remain largely unknown. Using nestin promoter-controlled LacZ
      reporter transgenic mice and mutant G93A-SOD1 transgenic mice mimicking ALS, we
      showed that there was an increase of NPC proliferation, migration, and
      neurogenesis in the lumbar region of adult spinal cord in response to motor
      neuron degeneration. The proliferation of NPCs detected by bromodeoxyurindine
      incorporation and LacZ staining was restricted to the ependymal zone surrounding
      the central canal (EZ). Once the NPCs moved out from the EZ, they lost the
      proliferative capability but maintained migratory function vigorously. During ALS
      like disease onset and progression, NPCs in the EZ migrated initially toward the
      dorsal horn direction and then to the ventral horn regions, where motor neurons
      have degenerated. More significantly, there was an increased de novo neurogenesis
      from NPCs during ALS-like disease onset and progression. The enhanced
      proliferation, migration, and neurogenesis of (from) NPCs in the adult spinal
      cord of ALS-like mice may play an important role in attempting to repair the
      degenerated motor neurons and restore the dysfunctional circuitry which resulted
      from the pathogenesis of mutant SOD1 in ALS.

PMID- 16099996
TI  - Isolation and angiogenesis by endothelial progenitors in the fetal liver.
AB  - Endothelial progenitor cells (EPCs) have significant therapeutic potential.
      However, the low quantity of such cells available from bone marrow and their
      limited capacity to proliferate in culture make their use difficult. Here, we
      present the first definitive demonstration of the presence of true EPCs in murine
      fetal liver capable of forming blood vessels in vivo connected to the host's
      vasculature after transplantation. This population is particularly interesting
      because it can be obtained at high yield and has a high angiogenic capacity as
      compared with bone marrow-derived EPCs. The EPC capacity is contained within the
      CD31+Sca1+ cell subset. We demonstrate that these cells are dependent for
      survival and proliferation on a feeder cell monolayer derived from the fetal
      liver. In addition, we describe a novel and easy method for the isolation and ex
      vivo proliferation of these EPCs. Finally, we used gene expression profiling and
      tandem mass spectrometry proteomics to examine the fetal liver endothelial
      progenitors and the feeder cells to identify possible proangiogenic growth factor
      and endothelial differentiation-associated genes.

PMID- 16099997
TI  - Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to
      dopaminergic neurons in vitro: potential therapeutic application for
      Parkinsonism.
AB  - Human mesenchymal stem cells isolated from Wharton's jelly of the umbilical cord
      were induced to transform into dopaminergic neurons in vitro through stepwise
      culturing in neuron-conditioned medium, sonic hedgehog, and FGF8. The success
      rate was 12.7%, as characterized by positive staining for tyrosine hydroxylase
      (TH), the rate-limiting catecholaminergic synthesizing enzyme, and dopamine being
      released into the culture medium. Transplantation of such cells into the striatum
      of rats previously made Parkinsonian by unilateral striatal lesioning with the
      dopaminergic neurotoxin 6-hydroxydopamine partially corrected the lesion-induced
      amphetamine-evoked rotation. Viability of the transplanted cells at least 4
      months after transplantation was identified by positive TH staining and migration
      of 1.4 mm both rostrally and caudally. These results suggest that human umbilical
      mesenchymal stem cells have the potential for treatment of Parkinson's disease.

PMID- 16099998
TI  - Interactions between human mesenchymal stem cells and natural killer cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent progenitor cells representing an
      attractive therapeutic tool for regenerative medicine. They possess unique
      immunomodulatory properties, being capable of suppressing T-cell responses and
      modifying dendritic cell differentiation, maturation, and function, whereas they
      are not inherently immunogenic, failing to induce alloreactivity to T cells and
      freshly isolated natural killer (NK) cells. To clarify the generation of host
      immune responses to implanted MSCs in tissue engineering and their potential use
      as immunosuppressive elements, the effect of MSCs on NK cells was investigated.
      We demonstrate that at low NK-to-MSC ratios, MSCs alter the phenotype of NK cells
      and suppress proliferation, cytokine secretion, and cyto-toxicity against HLA
      class I- expressing targets. Some of these effects require cell-to-cell contact,
      whereas others are mediated by soluble factors, including transforming growth
      factor-beta1 and prostaglandin E2, suggesting the existence of diverse mechanisms
      for MSC-mediated NK-cell suppression. On the other hand, MSCs are susceptible to
      lysis by activated NK cells. Overall, these data improve our knowledge of
      interactions between MSCs and NK cells and consequently of their effect on innate
      immune responses and their contribution to the regulation of adaptive immunity,
      graft rejection, and cancer immunotherapy.

PMID- 16099999
TI  - Bone marrow lacks a transplantable progenitor for smooth muscle type alpha-actin
      expressing cells.
AB  - While some studies have suggested that hematopoietic stem cells might give rise
      to other tissue types, others indicate that transdifferentiation would have to be
      an extremely rare event. We have now exploited smooth muscle type alpha-actin
      (alphaSMA) promoter-driven green fluorescent protein (GFP) transgenic mice
      (alphaSMA-GFP mice) for bone marrow transplantation to evaluate their potential
      to generate donor-type tissues in irradiation chimeras. There was a highly
      restricted pattern of GFP expression in the transgenic mice, marking bone marrow
      stromal cells and mesangial cells in the kidney. However, these characteristics
      were not transferable to wild-type animals given transgenic marrow cells even
      though hematopoietic cells were largely replaced. Our findings support earlier
      studies suggesting that the bone marrow microenvironment is difficult to
      transplant and indicate that hematopoietic stem cells are unlikely to give rise
      to alphaSMA-expressing progeny.

PMID- 16100000
TI  - Heat shock 70-kDa protein 8 isoform 1 is expressed on the surface of human
      embryonic stem cells and downregulated upon differentiation.
AB  - The cell-surface markers used routinely to define the undifferentiated state and
      pluripotency of human embryonic stem cells (hESCs) are those used in mouse
      embryonic stem cells (mESCs) because of a lack of markers directly originated
      from hESC itself. To identify more hESC-specific cell-surface markers, we
      generated a panel of monoclonal antibodies (MAbs) by immunizing the irradiated
      cell clumps of hESC line Miz-hES1, and selected 26 MAbs that were able to bind to
      Miz-hES1 cells but not to mESCs, mouse embryonic fibroblast cells, and STO cells.
      Most antibodies did not bind to human neural progenitor cells derived from the
      Miz-hES1 cells, either. Of these, MAb 20-202S (IgG1, kappa) immunoprecipitated a
      cell-surface protein of 72-kDa from the lysate of biotin-labeled Miz-hES1 cells,
      which was identified to be heat shock 70-kDa protein 8 isoform 1 (HSPA8) by
      quadrupole time-of-flight tandem mass spectrometry. Immunocytochemical analyses
      proved that the HSPA8 protein was also present on the surface of hESC lines Miz
      hES4, Miz-hES6, and HSF6. Two-color flow cytometric analysis of Miz-hES1 and HSF6
      showed the coexpression of the HSPA8 protein with other hESC markers such as
      stage-specific embryonic antigen 3 (SSEA3), SSEA4, TRA-1-60, and TRA-1-81. Flow
      cytometric and Western blot analyses using various cells showed that MAb 20-202S
      specifically bound to the HSPA8 protein on the surface of Miz-hES1, contrary to
      other anti-HSP70 antibodies examined. Furthermore, the surface expression of the
      HSPA8 protein on Miz-hES1 was markedly downregulated upon differentiation. These
      data indicate that a novel MAb 20-202S recognizes the HSPA8 protein on the
      surface of hESCs and suggest that the HSPA8 protein is a putative cell-surface
      marker for undifferentiated hESCs.

PMID- 16100001
TI  - Expression of neurodevelopmental markers by cultured porcine neural precursor
      cells.
AB  - Despite the increasing importance of the pig as a large animal model, little is
      known about porcine neural precursor cells. To evaluate the markers expressed by
      these cells, brains were dissected from 60-day fetuses, enzymatically
      dissociated, and grown in the presence of epidermal growth factor, basic
      fibroblast growth factor, and platelet-derived growth factor. Porcine neural
      precursors could be grown as suspended spheres or adherent monolayers, depending
      on culture conditions. Expanded populations were banked or harvested for analysis
      using reverse transcription-polymerase chain reaction (RT-PCR),
      immunocytochemistry, microarrays, and flow cytometry, and results compared with
      data from analogous human forebrain progenitor cells. Cultured porcine neural
      precursors widely expressed neural cell adhesion molecule (NCAM), polysialic acid
      (PSA)-NCAM, vimentin, Ki-67, and Sox2. Minority subpopulations of cells expressed
      doublecortin, beta-III tubulin, synapsin I, glial fibrillary acidic protein
      (GFAP), and aquaporin 4 (AQP4) consistent with increased lineage restriction. A
      human microarray detected porcine transcripts for nogoA (RTN4) and stromal cell
      derived factor 1 (SDF1), possibly cyclin D2 and Pbx1, but not CD133, Ki-67,
      nestin, or nucleostemin. Subsequent RT-PCR showed pig forebrain precursors to be
      positive for cyclin D2, nucleostemin, nogoA, Pbx1, vimentin, and a faint band for
      SDF1, whereas no signal was detected for CD133, fatty acid binding protein 7
      (FABP7), or Ki-67. Human forebrain progenitor cells were positive for all the
      genes mentioned. This study shows that porcine neural precursors share many
      characteristics with their human counterparts and, thus, may be useful in porcine
      cell transplantation studies potentially leading to the application of this
      strategy in the setting of nervous system disease and injury.

PMID- 16100002
TI  - Cell renewing in neuroblastoma: electrophysiological and immunocytochemical
      characterization of stem cells and derivatives.
AB  - We explored the stem cell compartment of the SH-SY5Y neuroblastoma (NB) clone and
      its development by a novel approach, integrating clonal and immunocytochemical
      investigations with patch-clamp measurements of ion currents simultaneously
      expressed on single cells. The currents selected were the triad IHERG, IKDR, INa,
      normally expressed at varying mutual ratios during development of neural crest
      stem cells, from which NB derives upon neoplastic transformation. These ratios
      could be used as electrophysiological clusters of differentiation (ECDs),
      identifying otherwise indistinguishable stages in maturation. Subcloning
      procedures allowed the isolation of highly clonogenic substrate-adherent (S-type)
      cells that proved to be p75- and nestinpositive and were characterized by a nude
      electrophysiological profile (ECDS0). These cells expressed negligible levels of
      the triad and manifested the capacity of generating the two following lineages:
      first, a terminally differentiating, smooth muscular lineage, positive for
      calponin and smooth muscle actin, whose electrophysiological profile is
      characterized by a progressive diminution of IHERG, the increase of IKDR and INa,
      and the acquisition of IKIR (ECDS2); second, a neuronal abortive pathway (NF-68
      positive), characterized by a variable expression of IHERG and IKDR and a low
      expression of INa (ECDNS). This population manifested a vigorous amplification,
      monopolizing the stem cell compartment at the expense of the smooth muscular
      lineage to such an extent that neuronal-like (N-type) cells must be continuously
      removed if the latter are to develop.

PMID- 16100003
TI  - Biological activities encoded by the murine mesenchymal stem cell transcriptome
      provide a basis for their developmental potential and broad therapeutic efficacy.
AB  - We used serial analysis of gene expression to catalog the transcriptome of murine
      mesenchymal stem cells (MSCs) enriched from bone marrow by immunodepletion.
      Interrogation of this database, results of which are delineated in the appended
      databases, revealed that immunodepleted murine MSCs (IDmMSCs) highly express
      transcripts encoding connective tissue proteins and factors modulating T-cell
      proliferation, inflammation, and bone turnover. Categorizing the transcriptome
      based on gene ontologies revealed the cells also expressed mRNAs encoding
      proteins that regulate mesoderm development or that are characteristic of
      determined mesenchymal cell lineages, thereby reflecting both their stem cell
      nature and differentiation potential. Additionally, IDmMSCs also expressed
      transcripts encoding proteins regulating angiogenesis, cell motility and
      communication, hematopoiesis, immunity and defense as well as neural activities.
      Immunostaining and fluorescence-activated cell sorting analysis revealed that
      expression of various regulatory proteins was restricted to distinct
      subpopulations of IDmMSCs. Moreover, in some cases, these proteins were absent or
      expressed at reduced levels in other murine MSC preparations or cell lines.
      Lastly, by comparing their transcriptome to that of 17 other murine cell types,
      we also identified 43 IDmMSC-specific transcripts, the nature of which reflects
      their varied functions in bone and marrow. Collectively, these results
      demonstrate that IDmMSC express a diverse repertoire of regulatory proteins,
      which likely accounts for their demonstrated efficacy in treating a wide variety
      of diseases. The restricted expression pattern of these proteins within
      populations suggests that the cellular composition of marrow stroma and its
      associated functions are more complex than previously envisioned.

PMID- 16100004
TI  - Unique gene expression signature by human embryonic stem cells cultured under
      serum-free conditions correlates with their enhanced and prolonged growth in an
      undifferentiated stage.
AB  - Understanding the interaction between human embryonic stem cells (hESCs) and
      their microenvironment is crucial for the propagation and the differentiation of
      hESCs for therapeutic applications. hESCs maintain their characteristics both in
      serum-containing and serum-replacement (SR) media. In this study, the effects of
      the serum-containing and SR culture media on the gene expression profiles of
      hESCs were examined. Although the expression of many known embryonic stem cell
      markers was similar in cells cultured in either media, surprisingly, 1,417 genes
      were found to be differentially expressed when hESCs cultured in serum-containing
      medium were compared with those cultured in SR medium. Several genes upregulated
      in cells cultured in SR medium suggested increased metabolism and proliferation
      rates in this medium, providing a possible explanation for the increased growth
      rate of nondifferentiated cells observed in SR culture conditions compared with
      that in serum medium. Several genes characteristic for cells with differentiated
      phenotype were expressed in cells cultured in serum-containing medium. Our data
      clearly indicate that the manipulation of hESC culture conditions causes
      phenotypic changes of the cells that were reflected also at the level of gene
      expression. Such changes may have fundamental importance for hESCs, and gene
      expression changes should be monitored as a part of cell culture optimization
      aiming at a clinical use of hESCs for cell transplantation.

PMID- 16100005
TI  - Hepatocyte growth factor effects on mesenchymal stem cells: proliferation,
      migration, and differentiation.
AB  - Hepatocyte growth factor (HGF), a pleiotropic cytokine of mesenchymal origin
      promoting migration, proliferation, and survival in a wide spectrum of cells, can
      also modulate different biological responses in stem cells, but the mechanisms
      involved are not completely understood so far. In this context, we show that
      short-term exposure of mesenchymal stem cells (MSCs) to HGF can induce the
      activation of its cognate Met receptor and the downstream effectors ERK1/2,
      p38MAPK, and PI3K/Akt, while long-term exposure to HGF resulted in cytoskeletal
      rearrangement, cell migration, and marked inhibition of proliferation through the
      arrest in the G1-S checkpoint. When added to MSCs, the K252A tyrosine kinase
      inhibitor prevented HGF-induced responses. HGF's effect on MSC proliferation was
      reversed by p38 inhibitor SB203580, while the effects on cell migration were
      abrogated by PI3K inhibitor Wortmannin, suggesting that HGF acts through
      different pathways to determine its complex effects on MSCs. Prolonged treatment
      with HGF induced the expression of cardiac-specific markers (GATA-4, MEF2C, TEF1,
      desmin, alpha-MHC, beta-MHC, and nestin) with the concomitant loss of the stem
      cell markers nucleostemin, c-kit, and CD105.

PMID- 16100006
TI  - Long-term proliferation of human embryonic stem cell-derived neuroepithelial
      cells using defined adherent culture conditions.
AB  - Research on the cell fate determination of embryonic stem cells is of enormous
      interest given the therapeutic potential in regenerative cell therapy. Human
      embryonic stem cells (hESCs) have the ability to renew themselves and
      differentiate into all three germ layers. The main focus of this study was to
      examine factors affecting derivation and further proliferation of multipotent
      neuroepithelial (NEP) cells from hESCs. hESCs cultured in serum-deprived defined
      medium developed distinct tube structures and could be isolated either by
      dissociation or adherently. Dissociated cells survived to form colonies of cells
      characterized as NEP when conditioned medium from human hepatocellular carcinoma
      HepG2 cell line (MEDII) was added. However, cells isolated adherently developed
      an enriched population of NEP cells independent of MEDII medium. Further
      characterization suggested that they were NEP cells because they had a similar
      phenotype profile to in vivo NEP cells and expression SOX1, SOX2, and SOX3 genes.
      They were positive for Nestin, a neural intermediate filament protein, and
      Musashi-1, a neural RNA-binding protein, but few cells expressed further
      differentiation markers, such as PSNCAM, A2B5, MAPII, GFAP, or O4, or other
      lineage markers, such as muscle actin, alpha fetoprotein, or the pluripotent
      marker Oct4. Further differentiation of these putative NEP cells gave rise to a
      mixed population of progenitors that included A2B5-positive and PSNCAM-positive
      cells and postmitotic neurons and astrocytes. To proliferate and culture these
      derived NEP cells, ideal conditions were obtained using neurobasal medium
      supplemented with B27 and basic fibroblast growth factor in 5% oxygen. NEP cells
      were continuously propagated for longer than 6 months without losing their
      multipotent cell characteristics and maintained a stable chromosome number.

PMID- 16100008
TI  - Pathogenesis of obstructive and central sleep apnea.
AB  - Considerable progress has been made over the last several decades in our
      understanding of the pathophysiology of both central and obstructive sleep apnea.
      Central sleep apnea, in its various forms, is generally the product of an
      unstable ventilatory control system (high loop gain) with increased controller
      gain (high hypercapnic responsiveness) generally being the cause. High plant gain
      can contribute under certain circumstances (hypercapnic patients). On the other
      hand, obstructive sleep apnea can develop as the result of a variety of
      physiologic characteristics. The combinations of these may vary considerably
      between patients. Most obstructive apnea patients have an anatomically small
      upper airway with augmented pharyngeal dilator muscle activation maintaining
      airway patency awake, but not asleep. However, individual variability in several
      phenotypic characteristics may ultimately determine who develops apnea and how
      severe the apnea will be. These include: (1) upper airway anatomy, (2) the
      ability of upper airway dilator muscles to respond to rising intrapharyngeal
      negative pressure and increasing Co(2) during sleep, (3) arousal threshold in
      response to respiratory stimulation, and (4) loop gain (ventilatory control
      instability). As a result, patients may respond to different therapeutic
      approaches based on the predominant abnormality leading to the sleep-disordered
      breathing.

PMID- 16100007
TI  - REM sleep-like atonia of hypoglossal (XII) motoneurons is caused by loss of
      noradrenergic and serotonergic inputs.
AB  - RATIONALE: Studies of hypoglossal (XII) motoneurons that innervate the
      genioglossus muscle, an upper airway dilator, suggested that the suppression of
      upper airway motor tone during REM sleep is caused by withdrawal of excitation
      mediated by norepinephrine and serotonin. OBJECTIVES: Our objectives were to
      determine whether antagonism of aminergic receptors located in the XII nucleus
      region can abolish the REM sleep-like atonia of XII motoneurons, and whether both
      serotonergic and noradrenergic antagonists are required to achieve this effect.
      METHODS: REM sleep-like episodes were elicited in anesthetized rats by pontine
      carbachol injections before and at various times after microinjection of prazosin
      and methysergide combined, or of only one of the drugs, into the XII nucleus.
      MEASUREMENTS AND MAIN RESULTS: Spontaneous XII nerve activity was significantly
      reduced, by 35 to 81%, by each antagonist alone and in combination, indicating
      that XII motoneurons were under both noradrenergic and serotonergic endogenous
      excitatory drives. During the 32 to 81 min after microinjections of both
      antagonists, pontine carbachol caused no depression of XII nerve activity,
      whereas other characteristic effects (activation of the hippocampal and cortical
      EEG, and slowing of the respiratory rate) remained intact. A partial recovery of
      the depressant effect of carbachol then occurred parallel to the recovery of
      spontaneous XII nerve activity from the depressant effect of the antagonists.
      Microinjections of either antagonist alone did not eliminate the depressant
      effect of carbachol. CONCLUSIONS: The REM sleep-like depression of XII
      motoneuronal activity induced by pontine carbachol can be fully accounted for by
      the combined withdrawal of noradrenergic and serotonergic effects on XII
      motoneurons.

PMID- 16100009
TI  - Endotoxin up-regulates interleukin-18: potential role for gram-negative
      colonization in sarcoidosis.
AB  - RATIONALE AND OBJECTIVES: Sarcoidosis is a granulomatous disease of unknown
      etiology characterized by a helper T-cell type 1-mediated process. Previously we
      demonstrated a role for interleukin-18 in sarcoidosis. Here we examine the
      regulation of interleukin-18 in this condition. METHODS: Cytokine levels in
      sarcoid epithelial lining fluid were measured by ELISA. We examined interleukin
      18 promoter activity and mRNA and protein levels in the epithelial lining fluid
      of individuals with active sarcoidosis, and of individuals recovered from
      sarcoidosis, in response to purified protein derivative of Mycobacterium
      tuberculosis, beryllium sulfate, zirconium sulfate, aluminum sulfate, and
      lipopolysaccharide. Endotoxin levels in the epithelial lining fluid of
      individuals with sarcoidosis, individuals recovered from sarcoidosis, and control
      subjects were assessed by Limulus amebocyte lysate analysis. Allele-specific
      polymerase chain reaction was used to genotype 94 patients with sarcoidosis and
      97 control subjects for the interleukin-18 -607(A/C) polymorphism. Species
      specific polymerase chain reaction identified bacterial DNA in fluid samples.
      RESULTS: Epithelial lining fluid from active sarcoids contained elevated levels
      of interleukin-18, interferon-gamma, and interleukin-12 compared with recovered
      patients and also contained significantly higher levels of endotoxin. Depletion
      of endotoxin from this epithelial lining fluid reduced its effect on the human
      interleukin-18 promoter in vitro. There was a higher frequency of the -607C
      allele and -607(C/C) genotype in the sarcoidosis population compared with control
      subjects; however, this was not associated with a functional response to
      endotoxin treatment. Finally, bacterial 16S rRNA from Haemophilus influenzae and
      Moraxella catarrhalis was detected in sarcoid fluid samples. CONCLUSIONS: The
      pathogenesis of sarcoidosis is propagated through the actions of a helper T-cell
      type 1-driven response. This study shows that gram-negative bacteria may
      contribute to this effect by upregulating interleukin-18 expression.

PMID- 16100010
TI  - Gelsolin secretion in interleukin-4-treated bronchial epithelia and in asthmatic
      airways.
AB  - RATIONALE: The airway surface liquid, the thin layer of liquid covering the
      airways, is essential for mucociliary clearance and as a barrier against
      microbial and other noxious agents. Proteins secreted into the airway surface
      liquid by epithelial and nonepithelial cells may be important in innate immunity
      and to improve the fluidity of mucous secretions. OBJECTIVES: We aimed to
      identify proteins specifically secreted into the airway surface liquid by human
      bronchial epithelial cells, in resting conditions and after treatment with
      interleukin 4 (IL-4), a cytokine released in asthma. METHODS AND MAIN RESULTS: By
      using a proteomics approach, we found that one of the most abundant proteins was
      gelsolin, which breaks down actin filaments. Gelsolin mRNA and protein secretion
      were increased threefold in the airway surface liquid of epithelia treated with
      IL-4. These results were confirmed at the functional level by measuring actin
      depolymerization using a fluorescence assay. Gelsolin protein was also
      upregulated in the airways of subjects with asthma. CONCLUSIONS: Our findings
      indicate that gelsolin is released by epithelial cells into the airways and that
      its secretion is increased by IL-4 in vitro. In addition, we found that the
      concentration of both IL-4 and gelsolin were raised in the bronchoalveolar lavage
      of patients with asthma. These results suggest that gelsolin might improve the
      fluidity of airway surface liquid in asthma by breaking down filamentous actin
      that may be released in large amounts by dying cells during inflammation.

PMID- 16100011
TI  - Computed tomography in the evaluation of cystic fibrosis lung disease.
AB  - The first report of computed tomography (CT) scanning to monitor cystic fibrosis
      (CF)-related lung disease was published in 1986. Further publications followed,
      but in general there was little interest in this technique until recently. Two
      factors in particular have led to this increased interest. First is an increasing
      realization that pulmonary function tests, long the mainstay of CF evaluation,
      often underestimate the presence and severity of mild and moderate lung disease.
      Second is the need for more sensitive outcome measures to assess new therapies.
      This had led to new interest and a series of important publications. The goal of
      this article is to present the current status of CT scanning in CF.

PMID- 16100012
TI  - Gene expression changes during the development of acute lung injury: role of
      transforming growth factor beta.
AB  - RATIONALE: Acute lung injury can occur from multiple causes, resulting in high
      mortality. The pathophysiology of nickel-induced acute lung injury in mice is
      remarkably complex, and the molecular mechanisms are uncertain. OBJECTIVES: To
      integrate molecular pathways and investigate the role of transforming growth
      factor beta (TGF-beta) in acute lung injury in mice. METHODS: cDNA microarray
      analyses were used to identify lung gene expression changes after nickel
      exposure. MAPPFinder analysis of the microarray data was used to determine
      significantly altered molecular pathways. TGF-beta1 protein in bronchoalveolar
      lavage fluid, as well as the effect of inhibition of TGF-beta, was assessed in
      nickel-exposed mice. The effect of TGF-beta on surfactant-associated protein B
      (Sftpb) promoter activity was measured in mouse lung epithelial cells.
      MEASUREMENTS AND MAIN RESULTS: Genes that decreased the most after nickel
      exposure play important roles in lung fluid absorption or surfactant and
      phospholipid synthesis, and genes that increased the most were involved in TGF
      beta signaling. MAPPFinder analysis further established TGF-beta signaling to be
      significantly altered. TGF-beta-inducible genes involved in the regulation of
      extracellular matrix function and fibrinolysis were significantly increased after
      nickel exposure, and TGF-beta1 protein was also increased in the lavage fluid.
      Pharmacologic inhibition of TGF-beta attenuated nickel-induced protein in
      bronchoalveolar lavage. In addition, treatment with TGF-beta1 dose-dependently
      repressed Sftpb promoter activity in vitro, and a novel TGF-beta-responsive
      region in the Sftpb promoter was identified. CONCLUSIONS: These data suggest that
      TGF-beta acts as a central mediator of acute lung injury through the alteration
      of several different molecular pathways.

PMID- 16100013
TI  - Role for CXCR6 and its ligand CXCL16 in the pathogenesis of T-cell alveolitis in
      sarcoidosis.
AB  - RATIONALE: Receptor expression dictates the spectrum of chemokine actions on
      immunocompetent cells. We have previously shown that the chemokine receptor CXCR3
      is highly expressed by T-helper type 1 (Th1) cells infiltrating the lungs of
      patients with sarcoidosis. OBJECTIVES: The evaluation of the role of Bonzo/CXCR6
      and its ligand CXCL16 in the pathogenesis of sarcoidosis. METHODS:
      Immunocompetent cells infiltrating sarcoid lung have been evaluated by flow
      cytometry, confocal microscopy, immunohistochemical and molecular analysis, and
      functional assays. MAIN RESULTS: Th1 cells isolated from the bronchoalveolar
      lavage of patients with sarcoidosis and T-cell alveolitis coexpressed CXCR3 and
      CXCR6. Immunohistochemical analysis of lung specimens has shown that CXCR6+ T
      cells infiltrated lung interstitium surrounding the central core of the
      granuloma. The CXCR6 ligand CXCL16 was abundantly expressed by macrophages
      infiltrating sarcoid tissue and/or forming the granuloma core. From a functional
      point of view, sarcoid Th1 cells were able to respond to CXCL10 and CXCL16 in
      migratory assay. In vitro kinetic studies demonstrated that, although CXCR3 was
      rapidly induced by interleukin (IL)-15 and IL-18, CXCR6 induction was slow (8 d)
      and mainly regulated by IL-15. CONCLUSIONS: T cells coexpressing CXCR3 and CXCR6
      act coordinately with respective ligands and Th1 inflammatory cytokines in the
      alveolitic/granuloma phases of the disease.

PMID- 16100014
TI  - Hypogonadism, quadriceps weakness, and exercise intolerance in chronic
      obstructive pulmonary disease.
AB  - RATIONALE: Circulating levels of testosterone and gonadotrophins of patients with
      chronic obstructive pulmonary disease (COPD) have never been compared with those
      of elderly men with normal pulmonary function. Moreover, the relationship of
      hypogonadism with quadriceps muscle weakness and exercise intolerance has been
      studied scarcely in men with COPD. OBJECTIVES: To compare circulating levels of
      hormones of the pituitary-gonadotrophic axis of men with COPD with those of age
      matched control subjects. Moreover, to study the relationship of hypogonadism
      with quadriceps muscle force, 6-min walking distance, and systemic markers of
      inflammation in the patients. METHODS AND MEASUREMENTS: Circulating levels of
      follicle-stimulating hormone, luteinizing hormone, testosterone, and sex hormone
      binding globulin were determined, and free testosterone was calculated in 78
      patients (FEV1: 44 +/- 17% of the predicted values) and 21 control subjects.
      Moreover, quadriceps muscle force, 6-min walking distance, number of pack-yr, and
      systemic inflammation were determined. MAIN RESULTS: Follicle-stimulating hormone
      and luteinizing hormone were higher in the patients, whereas testosterone was
      lower (p < or = 0.05). The latter finding was also present in 48 non-steroid
      using patients with normal blood gases. Low androgen status was significantly
      related to quadriceps muscle weakness (r = 0.48) and C-reactive protein (r = 
      0.39) in the patients, but not to exercise intolerance, the number of pack-yr, or
      increased circulating levels of interleukin 8 or soluble receptors of tumor
      necrosis factor alpha. CONCLUSIONS: In contrast to exercise intolerance,
      quadriceps muscle weakness is related to low circulating levels of testosterone
      in men with COPD.

PMID- 16100015
TI  - Computed tomography correlates with pulmonary exacerbations in children with
      cystic fibrosis.
AB  - RATIONALE: High-resolution computed tomography (HRCT) has been suggested as a
      potential outcome surrogate for cystic fibrosis (CF) lung disease. An important
      attribute of a valid outcome surrogate is that the surrogate reflects true
      clinical outcomes. OBJECTIVES: We performed this study to validate HRCT, a
      proposed surrogate outcome measure for CF lung disease, against a true clinical
      outcome, the number of respiratory tract exacerbations occurring in 2 yr, and to
      assess the correlation of CT scores and pulmonary function tests (PFTs) with this
      clinical outcome. METHODS: CTs and PFTs were performed on 6- to 10-yr-old
      children at the beginning and end of a 2-yr study during which the number of
      exacerbations were recorded. Spearman correlations and Poisson models were used
      to assess the correlation of the number of exacerbations with baseline values and
      changes in PFTs and CT scores. MEASUREMENTS AND MAIN RESULTS: Nine of 61 subjects
      had a total of 22 respiratory tract exacerbations. At baseline, PFTs and four CT
      scores showed significant correlation with number of exacerbations, but no
      variable by itself predicted exacerbations with high accuracy. For change over
      the 2-yr period, three CT scores showed significant correlation with
      exacerbations, whereas no PFTs showed significant correlation. CONCLUSION: This
      is the first study showing correlation between CT and a true clinical outcome.
      Change in CT scores correlates moderately well with the number of exacerbation.
      Poor correlation between change in FEV1 and exacerbations suggests that HRCT may
      be a more appropriate outcome surrogate for longitudinal studies of young
      children.

PMID- 16100016
TI  - Leukocyte count predicts microembolic Doppler signals during carotid stenting: a
      link between inflammation and embolization.
AB  - BACKGROUND AND PURPOSE: Protected stenting has emerged as a safe and effective
      alternative to endarterectomy for the treatment of carotid stenosis in patients
      at high operative risk. Distal microembolization occurs invariably during carotid
      stenting. Little is known about the relationship between systemic inflammation
      and embolization during carotid stenting. METHODS: We examined 43 consecutive
      patients who underwent carotid stenting with simultaneous transcranial Doppler
      (TCD) monitoring of the ipsilateral middle cerebral artery. Embolization was
      quantified by measuring microembolic signals (MES) on TCD. Preprocedure leukocyte
      counts were related to MES. RESULTS: In unadjusted analyses, preprocedure
      leukocyte count was positively correlated with total procedural MES (r2= 0.16;
      P=0.008). After considering age, gender, comorbidities, concomitant medical
      therapies, and the use of emboli prevention devices, increasing leukocyte count
      (beta=35 for each 1000/microL increment; P=0.018) remained a significant and
      independent predictor of embolization (model-adjusted r2=0.365; P=0.0005).
      CONCLUSIONS: Increasing preprocedure leukocyte count independently predicted more
      frequent MES during carotid stenting. These data suggest that systemic
      inflammation may influence the degree of procedural embolization.

PMID- 16100018
TI  - Social interaction improves experimental stroke outcome.
AB  - BACKGROUND AND PURPOSE: Social interaction can have a profound effect on health.
      The purpose of the present study was to determine whether affiliative social
      interactions before and after stroke improve ischemic outcomes as assessed
      through histological analysis and behavioral assays. METHODS: Male and female
      C57BL/6 mice were housed individually or with an ovariectomized female.
      Behavioral assessments were made 24 hours before 60 or 90 minutes of transient
      intraluminal middle cerebral artery occlusion (MCAO) or SHAM surgery and after 7
      days of reperfusion. Two hours after behavioral testing on day 7, infarct size
      was determined by 2,3,5-triphenyltetrazolium histology, and blood samples were
      collected for assessment of corticosterone and C-reactive protein (CRP)
      concentrations. RESULTS: Pair housing significantly decreased infarct size and
      improved contralateral paw use in 60-minute MCAO males and 90-minute MCAO females
      compared with socially isolated cohorts. Housing condition had no significant
      effect on infarct size in females that underwent 60 minutes of MCAO, but pair
      housing was associated with improved contralateral paw use relative to socially
      isolated mice. In a separate cohort of males, intraischemic CRP concentration was
      significantly reduced in pair-housed males relative to isolated males.
      CONCLUSIONS: Affiliative interaction during the peri-ischemic period reduces
      intraischemic CRP concentration, decreases ischemic damage in male and female
      mice, and improves behavioral outcome.

PMID- 16100019
TI  - Heme oxygenase-1 is expressed in carotid atherosclerotic plaques infected by
      Helicobacter pylori and is more prevalent in asymptomatic subjects.
AB  - BACKGROUND AND PURPOSE: It is not well established what are the features, if any,
      that distinguish symptomatic from asymptomatic carotid atherosclerotic plaques.
      Inducible heme oxygenase-1 (HO-1) is a component of cellular defense mechanisms
      against oxidative stress. We aimed to assess the presence of Helicobacter pylori
      (H pylori) and the expression of HO-1 in carotid atherosclerotic plaques of
      patients with and without prior neurologic symptoms attributable to the operated
      artery. METHODS: We examined 25 symptomatic and 23 asymptomatic carotid
      atherosclerotic plaques removed during endarterectomy and 7 normal carotid
      arteries obtained at autopsy. We investigated the presence of H pylori DNA in the
      vessel wall and performed immunohistochemical detection of HO-1. RESULTS: H
      pylori DNA was present in 28 plaques and HO-1 was expressed in 30 plaques. HO-1
      was found in 27 H pylori-positive specimens but in only 3 H pylori-negative
      specimens (P<0.001). All 7 normal carotid arteries were negative for both H
      pylori and HO-1. Although 82% of asymptomatic specimens were positive for H
      pylori and 87% for HO-1, only 36% of symptomatic specimens were positive for both
      H pylori and HO-1 (P<0.01). CONCLUSIONS: This study suggests a strong association
      between H pylori infection and expression of HO-1 in carotid atherosclerotic
      plaques. There was a substantial prevalence of these features in specimens
      obtained from asymptomatic subjects.

PMID- 16100021
TI  - Association of apolipoprotein E4 and haplotypes of the apolipoprotein E gene with
      lobar intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Conflicting reports in the literature exist with regard
      to the association of apolipoprotein E (apo E) alleles and lobar intracerebral
      hemorrhage (ICH). We genotyped 12 single-nucleotide polymorphisms in the 5'
      upstream regulatory, exonic, and intronic regions of the apo E gene and performed
      genotype and haplotype association analyses. METHODS: We prospectively enrolled
      subjects with hemorrhagic stroke and matched them with 2 controls based on age,
      race, and sex. Each case was reviewed by a physician to determine case status and
      location of the ICH. Multivariate logistic-regression modeling with backward
      elimination was used to determine significant risk factors for lobar ICH.
      Associations at the genotype and haplotype levels and linkage disequilibrium were
      conducted according to standard statistical methods. RESULTS: Between May 1997
      and December 2002, 315 cases of ICH were recruited, of whom 107 were lobar ICH
      cases matched to 205 controls. No association was found for apo E2, E3, or E4
      with nonlobar ICH. Independent, significant risk factors for lobar ICH included
      apo E4, untreated hypertension, anticoagulant use, a first-degree relative with
      ICH, and < or =high school education (compared with >high school education).
      Treated hypercholesterolemia compared with "no history of hypercholesterolemia"
      was associated with a decreased risk of lobar ICH. Haplotype association analysis
      demonstrated a significant association of the apo E gene with lobar ICH among
      whites (P<0.0001) and blacks (P=0.0024). CONCLUSIONS: Apo E4 is independently
      associated with lobar ICH but not nonlobar ICH. Haplotypes of the apo E gene are
      associated with lobar ICH. Untreated hypertension is a risk factor for lobar ICH.

PMID- 16100022
TI  - Antiplatelet agents in secondary prevention of stroke: a perspective.
AB  - BACKGROUND AND PURPOSE: Antiplatelet agents are widely used in the secondary
      prevention of stroke and other vascular events. The purpose of this review is to
      give a perspective of the factors involved in clinical practice for selecting
      antiplatelet drugs appropriate to the patient population. SUMMARY OF REVIEW:
      Aspirin remains the most popular drug, because it is modestly effective
      (approximately 25% risk reduction); however, it has undesirable side effects that
      are sometimes serious. The nonaspirin compounds are marginally more effective but
      are much more expensive and subject to commercial pressures from industry. A
      completely new look at these compounds is necessary, rather than spending more
      precious resources on "drug wars" that are expensive in time and money.
      CONCLUSIONS: A "polypill" has been previously proposed, and possibly a
      combination of drugs targeted at the major vascular risk factors that is given to
      patients within 24 hours of initial stroke symptoms and to clearly defined
      patient populations may prove a solution.

PMID- 16100023
TI  - Promoter polymorphisms in the nitric oxide synthase 3 gene are associated with
      ischemic stroke susceptibility in young black women.
AB  - BACKGROUND AND PURPOSE: Endothelial nitric oxide exerts a variety of protective
      effects on endothelial cells and blood vessels, and therefore the nitric oxide
      synthase 3 gene (NOS3) is a logical candidate gene for stroke susceptibility.
      METHODS: We used the population-based Stroke Prevention in Young Women case
      control study to assess the association of five NOS3 polymorphisms in 110 cases
      (46% black) with ischemic stroke and 206 controls (38% black), 15 to 44 years of
      age. Polymorphisms included 3 single nucleotide polymorphisms (SNPs) in the
      promoter region (-1468 T>A, -922 G>A, -786 T>C), 1 SNP in exon 7 (G894T), and 1
      insertion/deletion polymorphism within intron 4. RESULTS: Significant
      associations with both the -922 G>A and -786 T>C SNPs with ischemic stroke were
      observed in the black, but not the white, population. This association was
      attributable to an increased prevalence of the -922 A allele (OR=3.0, 95% CI=1.3
      to 6.8; P=0.005) and the -786 T allele (OR=2.9, 95% CI=1.3 to 6.4; P=0.005) in
      cases versus controls. These 2 SNPs were in strong linkage disequilibrium
      (D'=1.0), making it impossible to determine, within the confines of this genetic
      study, whether 1 or both of these polymorphisms are functionally related to NOS3
      expression. Two sets of haplotypes were also identified, 1 of which may confer an
      increased susceptibility to stroke in blacks, whereas the other appears to be
      protective. CONCLUSIONS: Promoter variants in NOS3 may be associated with
      ischemic stroke susceptibility among young black women.

PMID- 16100024
TI  - Cerebral vein and dural sinus thrombosis in elderly patients.
AB  - BACKGROUND AND PURPOSE: The clinical features and prognosis of cerebral vein and
      dural sinus thrombosis (CVT) in elderly patients have not been previously
      described. METHODS: In a multicenter prospective observational study, we compared
      clinical and imaging features, risk factors, and outcome of adult patients aged
      <65 (young and middle-aged patients) and > or =65 years (elderly patients).
      RESULTS: A total of 624 adult patients with CVT were registered and followed-up
      for a median of 16 months. Fifty-one (8.2%) were aged > or =65 years.
      Presentation as an isolated intracranial hypertension syndrome was less frequent
      in elderly patients (4/51 versus 139/573, P=0.008), whereas depressed
      consciousness (17 versus 97, P=0.005), and mental status changes (22 versus 115,
      P=0.001) were more frequent in the elderly. The prognosis of elderly patients was
      considerably worse than that of younger patients, as only 49% of elderly patients
      made a complete recovery (versus 82% in younger patients), whereas 27% died and
      22% were dependent at the end of follow-up (versus 7 and 2% respectively in
      younger patients). Carcinoma (5 cases) was more frequent as a risk factor for CVT
      in elderly patients (P=0.017). During follow-up, elderly patients were more
      likely to experience thrombotic events (HR=4.8, 95% CI=1.9 to 11.9) and were less
      likely to experience severe headaches (HR=0.2, 95% CI=0.02, 0.97). CONCLUSIONS:
      Elderly patients with CVT have a distinctive clinical presentation: isolated
      intracranial hypertension is uncommon, whereas mental status and alertness
      disturbances are common. The prognosis of CVT is worse in elderly patients.

PMID- 16100025
TI  - Baroreflex sensitivity is impaired in bilateral carotid atherosclerosis.
AB  - BACKGROUND AND PURPOSE: The arterial baroreflex is an important determinant of
      the short-term regulation of blood pressure and cardiovascular variability. The
      purpose of our study was to determine whether baroreflex sensitivity (BRS) and
      heart rate (HR) variability are altered in patients with carotid atherosclerosis
      (CA) and to assess the impact of characteristics of CA on BRS. METHODS: BRS and
      HR variability were prospectively evaluated in 75 consecutive patients undergoing
      carotid duplex examination in our neurosonology unit. Resting BRS was measured
      with the sequence method. HR variability was evaluated using spectral analysis.
      RESULTS: BRS was significantly reduced in patients with bilateral CA compared
      with patients without CA (P=0.015) and patients with unilateral CA (P=0.045). BRS
      was unaltered in patients with unilateral CA compared with patients with no CA.
      BRS was already reduced in mild (stenosis <50%), bilateral CA and was not further
      impaired in more severe CA. The association of BRS impairment with bilateral CA
      remained significant after adjustment for age, hypertension, and a history of
      stroke or transient ischemic attack. The study of HR variability demonstrated a
      reduction in the power of high-frequency band in patients with bilateral CA
      compared with patients with unilateral CA or without CA (P=0.015). CONCLUSIONS:
      Bilateral CA is associated with an impairment of BRS and a shift of the
      sympathovagal balance toward a relative decrease of the parasympathetic component
      of HR variability. These changes are already present in mild, bilateral CA.

PMID- 16100026
TI  - The linear behavior of the system middle cerebral artery flow velocity and blood
      pressure in patients with migraine: lack of autonomic control?
AB  - BACKGROUND AND PURPOSE: Migraine is considered a disorder of the autonomic
      nervous system. We used the frequency analysis of dynamic cerebral autoregulation
      to assess whether blood flow regulation disturbances can be found at the
      frequencies at which sympathetic and parasympathetic activity is present.
      METHODS: We measured simultaneously mean arterial blood pressure (BP) and the
      mean blood velocity (V) in the middle cerebral artery using transcranial Doppler
      ultrasound in 33 healthy controls (mean age+/-SD; 36+/-13 years) and in 22
      patients with migraine (mean age; 39+/-7 years). Apart from assessing spectral
      power density for BP and V, we calculated the transfer function parameters gain,
      phase, and coherence at the frequency range between 0.0 and 0.25 Hz. RESULTS:
      Compared with the controls, the spectral power density of BP and V exhibited a
      maximum magnitude of 10(26) in the migraine patients, whereas the maximum
      magnitude of BP and V in the controls was 10(-3). Coherence showed no difference
      between patients and controls. Gain between BP and V increased in the controls
      >0.01 Hz but was approximately 0 or negative in the migraine patients over the
      whole frequency range (P<0.01). The usually observed phase lead of V against BP
      was absent in the migraine patients in whom BP leaded V over nearly the whole
      frequency range (P<0.01). CONCLUSIONS: In terms of phase and gain, dynamic
      cerebral autoregulation is completely different in migraine patients compared
      with healthy subjects. Insofar, this can be interpreted as a lack of sympathetic
      and parasympathetic control of cerebral blood flow.

PMID- 16100027
TI  - Comparative overview of brain perfusion imaging techniques.
AB  - BACKGROUND AND PURPOSE: Numerous imaging techniques have been developed and
      applied to evaluate brain hemodynamics. Among these are positron emission
      tomography, single photon emission computed tomography, Xenon-enhanced computed
      tomography, dynamic perfusion computed tomography, MRI dynamic susceptibility
      contrast, arterial spin labeling, and Doppler ultrasound. These techniques give
      similar information about brain hemodynamics in the form of parameters such as
      cerebral blood flow or cerebral blood volume. All of them are used to
      characterize the same types of pathological conditions. However, each technique
      has its own advantages and drawbacks. SUMMARY OF REVIEW: This article addresses
      the main imaging techniques dedicated to brain hemodynamics. It represents a
      comparative overview established by consensus among specialists of the various
      techniques. CONCLUSIONS: For clinicians, this article should offer a clearer
      picture of the pros and cons of currently available brain perfusion imaging
      techniques and assist them in choosing the proper method for every specific
      clinical setting.

PMID- 16100028
TI  - Progressive symptomatic carotid dissection treated with multiple stents.
AB  - BACKGROUND AND PURPOSE: Internal carotid artery (ICA) dissection remains a major
      cause of stroke in the young. Although systemic anticoagulation and antiplatelet
      therapy allow healing of the dissection in most patients, medical treatment can
      fail or be contraindicated. In selected cases of carotid dissections, the use of
      endovascular stent-assisted angioplasty has been reported to permit
      reconstruction of the extracranial ICA. METHODS: We report a case of symptomatic
      spontaneous carotid dissection which progressively extended from the cervical to
      the supraclinoid segments of the ICA in a 48-year-old patient under anticoagulant
      therapy. Because of failed medical therapy and further transient ischemic attacks
      (TIAs), the patient was treated by 5 tandem stents deployed in an overlapping
      fashion from the terminal ICA to the cervical segment. RESULTS: Postprocedure
      angiography demonstrated reconstitution of the luminal diameter of the ICA. The
      patient progressively improved and no further TIAs were observed. At 8-month
      follow-up, the vessel remained patent with a slight intra-extracranial reduction
      in size suggesting myointimal hyperplasia. Neurological exam was normal.
      CONCLUSIONS: The successful angiographic and clinical results observed in our
      case of intra-extracranial stenting of a long dissection contributes to the
      literature of carotid dissection treated with multiple stents. The excellent mid
      term follow-up in our patient confirms the efficacy of this treatment and good
      tolerance to multiple stents. To our knowledge this is the first case of
      spontaneous dissection treated with stenting including the distal supraclinoid
      segment, through an extensive proximally dissected artery.

PMID- 16100029
TI  - Is it time for a large, collaborative study of pediatric stroke?
AB  - BACKGROUND AND PURPOSE: A 2002 report from the National Institute of Neurological
      Disorders and Stroke cited the critical importance of more childhood stroke
      studies. We present the incidence rate of pediatric stroke from a biethnic
      community-based project and calculate the population size required for future
      prospective studies of pediatric stroke. METHODS: This work is part of the Brain
      Attack Surveillance in Corpus Christi (BASIC) project. The community of 325,000
      is located in southeast Texas and is composed of approximately equal numbers of
      Mexican Americans (MAs) and non-Hispanic whites (NHWs). Discharge diagnosis codes
      from all hospitals in the county were used to identify cases of childhood stroke
      (age >1 month and <20 years) in 2002 and 2003, and stroke cases were validated by
      source document review. On the basis of the incidence rates, the population size
      required to complete a case-control study to examine risk factors for pediatric
      stroke was calculated. RESULTS: Eight cases of pediatric stroke were identified,
      yielding an annual incidence rate of 4.3 per 100,000 (95% CI, 1.9 to 8.5). There
      were 5 cases of intracerebral hemorrhage, 1 subarachnoid hemorrhage, 1 ischemic
      stroke, and 1 transient ischemic attack. All of the events occurred in MAs.
      Depending on the prevalence of the risk factors of interest, future studies of
      pediatric stroke would have to draw from a population of up to 59 million
      children to complete a case-control study within 4 years. CONCLUSIONS: Given the
      rarity of pediatric stroke, future studies will require multicenter efforts and
      possibly a national surveillance system.

PMID- 16100032
TI  - The prediction of malignant cerebral infarction by molecular brain barrier
      disruption markers.
AB  - BACKGROUND AND PURPOSE: Space-occupying brain edema is a life-threatening
      complication in patients with large hemispheric stroke. The aim of the study was
      to determine whether molecular markers of endothelial damage may help to predict
      secondary brain edema and, secondly, to identify patients who could benefit from
      aggressive therapies such as decompressive hemicraniectomy or hypothermia.
      METHODS: We studied 40 consecutive patients with malignant middle cerebral artery
      (MCA) infarction and 35 controls with massive MCA infarctions <70 years of age
      and matched by stroke severity on admission. Cranial computed tomography (CT) was
      performed at entry and repeated between days 4 and 7, or earlier if there was
      neurological worsening. Malignant MCA (m-MCA) infarction was diagnosed when
      follow-up CT detected a more than two-thirds space-occupying MCA infarction with
      midline shift, compression of the basal cisterns, and neurological deterioration.
      Plasma concentrations of glutamate, glycine, gamma-aminobutyric acid, interleukin
      6 (IL-6), IL-10, tumor necrosis factor-alpha, matrix metalloproteinase-9 (MMP-9),
      and cellular-fibronectin (c-Fn) were determined in blood samples obtained at
      admission. RESULTS: Mean time from stroke onset to blood sampling was 6.3+/-4.8
      in m-MCA and 7.7+/-6.0 hours in the control group (P=0.63). Baseline
      characteristics were comparable in both groups. c-Fn and MMP-9 levels were
      significantly higher in patients with m-MCA than in controls (all P<0.001). c-Fn
      >16.6 microg/mL had the highest sensitivity (90%), specificity (100%), and
      negative and positive predictive values (89% and 100%, respectively) for the
      prediction of m-MCA infarction. CONCLUSIONS: A plasma c-Fn concentration >16.6
      microg/mL at admission is associated with the development of m-MCA infarction
      with high sensitivity and specificity, suggesting that c-Fn might be useful in
      therapeutic decision making.

PMID- 16100033
TI  - Assessment of hemostatic risk factors in predicting arterial thrombotic events.
AB  - Arterial thrombosis results from endovascular injury and, to a lesser extent,
      alterations in hemostatic equilibrium. Although multiple hereditary and acquired
      hemostatic risk factors have been described in the pathophysiology of venous
      thrombosis, the degree and type of abnormalities that contribute to arterial
      thrombosis are less well understood. Endothelial cell injury with the elaboration
      of proinflammatory mediators stimulates the process of arterial thrombosis.
      Although this is most often the result of endovascular injury attributable to
      atherosclerotic disease, other disease states can elicit a similar response as
      well. Similarly, once thrombosis has been initiated, variations in the activity
      of coagulation proteins and endogenous anticoagulants, as well as the kinetics of
      platelet aggregation, may alter the effectiveness of thrombus formation.
      Epidemiological studies have identified several acquired or inherited states that
      may result in endothelial damage or altered hemostatic equilibrium, thereby
      predisposing patients to arterial thrombosis. These include hyperhomocysteinemia,
      elevated C-reactive protein, antiphospholipid antibodies, elevated fibrinogen,
      Factor VII, plasminogen activator inhibitor-1 (PAI-1), hereditary thrombophilias,
      and platelet hyper-reactivity. This review explores our present understanding of
      these risk factors in the development of arterial thrombotic events. At present,
      the literature supports a role for hyperhomocysteinemia, elevated C-reactive
      protein, and elevated fibrinogen as risk factors for arterial thrombosis.
      Similarly, the literature suggests that lupus anticoagulants and, to a lesser
      extent, elevated titers of cardiolipin IgG antibodies predispose to arterial
      vascular events. In certain subsets of patients, including those with concomitant
      cardiac risk factors, <55 years of age, and women, hereditary thrombophilias such
      as carriership of the factor V Leiden and the prothrombin G20210A mutations may
      confer a higher risk of arterial thrombosis. However, the data on Factor VII, PAI
      1, and platelet receptor polymorphisms are contradictory or lacking.

PMID- 16100034
TI  - Extracellular signal-regulated kinase-dependent stabilization of hepatic low
      density lipoprotein receptor mRNA by herbal medicine berberine.
AB  - OBJECTIVE: Our recent studies identified berberine (BBR) as a novel cholesterol
      lowering drug that upregulates low-density lipoprotein (LDL) receptor expression
      through mRNA stabilization. Here, we investigated mechanisms underlying
      regulatory effects of BBR on LDL receptor (LDLR) messenger. METHODS AND RESULTS:
      We show that the extracellular signal-regulated kinase (ERK) signaling pathway is
      used primarily by BBR to attenuate the decay of LDLR mRNA in HepG2 cells. Using
      different reporter constructs, we demonstrate that BBR affects LDLR mRNA
      stability entirely through 3' untranslated region (UTR) in an ERK-dependent
      manner, and this stabilizing effect is more prominent in liver-derived cells than
      nonhepatic cell lines. In contrast to BBR, the mRNA stabilizing effect of bile
      acid chenodeoxycholic acid is mediated through the LDLR coding sequence, whereas
      the 5'UTR, 3'UTR, and the coding sequence of LDLR mRNA are all implicated in the
      action of phorbol 12-myristate 13-acetate. By performing UV cross-linking and SDS
      PAGE, we identify 2 cytoplasmic proteins of 52 and 42 kDa that specifically bind
      to the LDLR 3'UTR in BBR-inducible and ERK-dependent manners. CONCLUSIONS: These
      new findings demonstrate that the BBR-induced stabilization of LDLR mRNA is
      mediated by the ERK signaling pathway through interactions of cis-regulatory
      sequences of 3'UTR and mRNA binding proteins that are downstream effectors of
      this signaling cascade.

PMID- 16100035
TI  - In vivo clearance of human protein S in a mouse model: influence of C4b-binding
      protein and the Heerlen polymorphism.
AB  - OBJECTIVE: To explore the effect of the Heerlen polymorphism and C4b-binding
      protein (C4BP) on protein S catabolism in vitro and in vivo. METHODS AND RESULTS:
      Radiolabeled protein S was efficiently bound and intracellularly degraded by THP
      1 macrophages, and both processes were strongly reduced in the presence of the
      protein S-carrier protein C4BP. To test whether C4BP displays a similar
      protective effect in vivo, survival experiments were performed in mice. In the
      absence of C4BP, radiolabeled human protein S disappeared in a biphasic manner
      (mean residence time [MRT] 2 hours). However, the presence of C4BP resulted in a
      4-fold prolonged survival of protein S (MRT 8 hours; P<0.0001). We also applied
      this experimental model to recombinant protein S-Heerlen, a naturally occurring
      variant that contains a Ser460Pro substitution. These clearance experiments
      revealed a strongly decreased survival of recombinant protein S-S460P (MRT 0.6
      hours; P=0.021), which could be compensated partially by C4BP (MRT 1.4 hours;
      P=0.012 compared with protein S-S460P). CONCLUSIONS: Protein S-S460P has a
      reduced survival in vivo, which may explain the low levels of free protein S in
      individuals carrying this polymorphism. Furthermore, C4BP prevents premature
      clearance of protein S and uses this ability to compensate the increased
      clearance of protein S-S460P.

PMID- 16100036
TI  - Advanced glycosylation end products might promote atherosclerosis through
      inducing the immune maturation of dendritic cells.
AB  - OBJECTIVE: Both advanced glycosylation end products (AGEs) and dendritic cells
      (DCs) have been shown to play a causative role in atherosclerosis. However,
      whether they function interactively in the process remains uncertain. We
      therefore studied the effects of AGE-bovine serum albumin (AGE-BSA) on the
      maturation of DCs and the expressions of scavenger receptor-A (SR-A) and receptor
      for AGEs (RAGE) on DCs. METHODS AND RESULTS: AGE-BSA induced DCs maturation
      accompanied with increased expressions of CD1a, CD40, CD80, CD83, CD86, and MHC
      class II. The capacity of DCs to stimulate T-cell proliferation and secretion of
      cytokines (interferon [IFN], IFN-gamma, interleukin [IL]-10 and IL-12) was also
      enhanced by AGE-BSA. AGE-BSA significantly upregulated SR-A and RAGE expression
      on DCs and the upregulation was abolished by inhibition of mitogen-activated
      protein (MAP) kinase Jnk, but not by that of Erk and p38 MAP kinase. AGE-BSA
      induced expression of CD83 and secretion of IL-12 were partly inhibited by either
      an anti-RAGE neutralizing antibody or a Jnk inhibitor. CONCLUSIONS: AGE-BSA
      induces maturation of DCs and augmented their capacity to stimulate T-cell
      proliferation and cytokine secretions possibly through upregulation of RAGE and
      SR-A, which at least in part through Jnk. These findings might explain in part
      the interactive roles of AGEs and DCs in the processes of atherosclerosis.

PMID- 16100037
TI  - Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in
      resistance arteries of angiotensin II-infused macrophage colony-stimulating
      factor-deficient mice: evidence for a role in inflammation in angiotensin-induced
      vascular injury.
AB  - OBJECTIVE: Angiotensin (Ang) II-induced vascular damage may be partially mediated
      by reactive oxygen species generation and inflammation. Homozygous osteopetrotic
      mice (Op/Op), deficient in macrophage colony-stimulating factor (m-CSF), exhibit
      reduced inflammation. We therefore investigated Ang II effects on vascular
      structure, function, and oxidant stress generation in this model. METHODS AND
      RESULTS: Adult Op/Op, heterozygous (Op/+), and wild type (+/+) mice underwent 14
      day Ang II (1000 ng/kg per minute) or saline infusion. Blood pressure (BP) was
      assessed by radiotelemetry, mesenteric resistance artery vascular reactivity was
      studied on a pressurized myograph, and vascular superoxide and NAD(P)H oxidase
      activity by lucigenin chemiluminescence. Ang II increased BP in Op/+ and +/+ mice
      but not in Op/Op. Ang II-treated Op/+ and +/+ mice showed reduced acetylcholine
      mediated relaxation (maximal relaxation, respectively, 64% and 67% versus 84% and
      93% in respective controls; P<0.05), which was unaffected by L-NAME. Ang II
      infused Op/Op mice arteries showed significantly less endothelial dysfunction
      than vehicle-infused counterparts (maximal relaxation 87% versus 96% in shams).
      Resistance arteries from Ang II-infused +/+ and Op/+ mice had significantly
      increased media-to-lumen ratio and media thickness, neither of which was altered
      in Op/Op mice compared with untreated littermates. Vascular media cross-sectional
      area, NAD(P)H oxidase activity and expression, and vascular cell adhesion
      molecule (VCAM)-1 expression were significantly increased by Ang II only in +/+
      mice (P<0.05). CONCLUSIONS: m-CSF-deficient mice (Op/Op) developed less
      endothelial dysfunction, vascular remodeling, and oxidative stress induced by Ang
      II than +/+ littermates, suggesting a critical role of m-CSF and proinflammatory
      mediators in Ang II-induced vascular injury.

PMID- 16100038
TI  - Iron chelation suppresses ferritin upregulation and attenuates vascular
      dysfunction in the aorta of angiotensin II-infused rats.
AB  - OBJECTIVE: We have investigated whether long-term administration of angiotensin
      (Ang) II causes ferritin induction and iron accumulation in the rat aorta, and
      their possible relation to regulatory effects on gene expression and vascular
      function in Ang II-infused animals. METHODS AND RESULTS: Sprague-Dawley rats were
      given Ang II for 7 days via subcutaneously implanted osmotic minipumps. Ang II
      infusion caused a >20-fold increase in ferritin protein expression over control
      values. Immunohistochemistry showed that Ang II infusion markedly increased the
      ferritin expression in the aortic endothelial and adventitial cells, with some of
      the latter being identified as monocytes/macrophages. Prussian blue staining
      showed that stainable iron was observed in the adventitial layer of aorta from
      Ang II-infused animals, but not in the endothelial layer. Chelation of iron
      suppressed aortic induction of ferritin and also the oxidative stress markers,
      heme oxygenase-1 and 4-hydroxynonenal-modified protein adducts. In addition, iron
      chelation attenuated Ang II-induced impairment of aortic relaxations in response
      to acetylcholine and sodium nitroprusside and suppressed upregulation of mRNA
      levels of monocyte chemoattractant protein-1. Iron chelation also partially
      attenuated the medial thickening and perivascular fibrosis induced by Ang II
      infusion for 4 weeks. CONCLUSIONS: Ang II infusion caused ferritin induction and
      iron deposition in the aortas. These phenomena might have a role in the
      regulation of gene expression, impairment of vascular function, and arterial
      remodeling induced by Ang II, which are presumably mediated in part by
      enhancement of oxidative stress.

PMID- 16100039
TI  - Bone morphogenetic protein 4 promotes pulmonary vascular remodeling in hypoxic
      pulmonary hypertension.
AB  - We show that 1 of the type II bone morphogenetic protein (BMP) receptor ligands,
      BMP4, is widely expressed in the adult mouse lung and is upregulated in hypoxia
      induced pulmonary hypertension (PH). Furthermore, heterozygous null Bmp4(lacZ/+)
      mice are protected from the development of hypoxia-induced PH, vascular smooth
      muscle cell proliferation, and vascular remodeling. This is associated with a
      reduction in hypoxia-induced Smad1/5/8 phosphorylation and Id1 expression in the
      pulmonary vasculature. In addition, pulmonary microvascular endothelial cells
      secrete BMP4 in response to hypoxia and promote proliferation and migration of
      vascular smooth muscle cells in a BMP4-dependent fashion. These findings indicate
      that BMP4 plays a dominant role in regulating BMP signaling in the hypoxic
      pulmonary vasculature and suggest that endothelium-derived BMP4 plays a direct,
      paracrine role in promoting smooth muscle proliferation and remodeling in hypoxic
      PH.

PMID- 16100040
TI  - Cardiac-specific loss of N-cadherin leads to alteration in connexins with
      conduction slowing and arrhythmogenesis.
AB  - The remodeling of ventricular gap junctions, as defined by changes in size,
      distribution, or function, is a prominent feature of diseased myocardium.
      However, the regulation of assembly and maintenance of gap junctions remains
      poorly understood. To investigate N-cadherin function in the adult myocardium, we
      used a floxed N-cadherin gene in conjunction with a cardiac-specific tamoxifen
      inducible Cre transgene. The mutant animals appeared active and healthy until
      their sudden death approximately 2 months after deleting N-cadherin from the
      heart. Electrophysiologic analysis revealed abnormal conduction in the ventricles
      of mutant animals, including diminished QRS complex amplitude consistent with
      loss of electrical coupling in the myocardium. A significant decrease in the gap
      junction proteins, connexin-43 and connexin-40, was observed in N-cadherin
      depleted myocytes. Perturbation of connexin function resulted in decreased
      ventricular conduction velocity, as determined by optical mapping. Our data
      suggest that perturbation of the N-cadherin/catenin complex in heart disease may
      be an underlying cause, leading to the establishment of the arrythmogenic
      substrate by destabilizing gap junctions at the cell surface.

PMID- 16100041
TI  - Effects of estrogen replacement therapies on mouse platelet function and
      glycoprotein VI levels.
AB  - Clinical trials have shown estrogen replacement therapy (ERT) is associated with
      adverse arterial vascular events. Arterial thrombosis is initiated by platelet
      activation, but the in vivo effects of estrogens on platelet function are not
      well understood. We used a murine model of menopause to examine 3 major ERT
      regimes and test the hypothesis that ERT affects the intrinsic platelet response
      to agonists. The 3 ERT regimes studied were: (1) oral conjugated equine estrogen
      (CEE), (2) oral 17-beta estradiol (E2), and (3) subcutaneously implanted E2 (SQ
      E2). Paired ovariectomized littermates were treated with these regimes or placebo
      for 21 days. Two platelet agonists, thrombin and the GPVI-specific agonist
      collagen-related peptide (COL-RP), were used to evaluate platelet reactivity.
      Among the 3 regimens, (1) oral CEE enhanced platelet reactivity to COL-RP, (2)
      oral E2 had no effect on platelet reactivity to COL-RP and (3) SQ E2 increased
      platelet sensitivity to thrombin but lowered reactivity to COL-RP. Thus, the in
      vivo effects of estrogen on platelet function are agonist specific and dependent
      on hormone formulation and mode of delivery. The GPVI collagen receptor likely
      mediated some of these effects, because the ERT regimens induced changes in
      platelet surface GPVI expression corresponding to the observed platelet
      activation.

PMID- 16100042
TI  - Alterations in internal elastic lamina permeability as a function of age and
      anatomical site precede lesion development in apolipoprotein E-null mice.
AB  - Early atherosclerosis is characterized by the accumulation of plasma-borne
      macromolecules (eg, low-density lipoproteins) in the arterial intima, which is
      bordered by endothelial cells (EC) and the internal elastic lamina (IEL). This
      accumulation is believed to be secondary to increased EC permeability. We
      hypothesized that a decrease in IEL permeability may precede lesion development
      and contribute to macromolecular accumulation. To test this hypothesis, we
      quantified EC and IEL permeability in lesion-free areas of the thoracic and
      abdominal aortas of chow-fed C57BL/6 control and atherosclerotic-prone
      apolipoprotein E (apoE)-null mice at 3 and 5 months of age. Between 3 and 5
      months of age, apoE-null mice begin to develop atherosclerotic lesions in the
      thoracic aorta. No significant differences in EC and IEL permeability were
      observed at either time in C57BL/6 control mice. In contrast, 78% and 19%
      decreases in IEL permeability of the thoracic aorta and abdominal aorta,
      respectively, were observed between 3 to 5 months of age in apoE-null mice
      (thoracic: 2.05+/-1.33 and 0.44+/-0.15 microm/min, P<0.001; abdominal: 1.13+/
      0.58 and 0.93+/-0.44 microm/min, P<0.05). To further determine whether decreased
      IEL permeability is linked with atherosclerotic lesion development, we quantified
      IEL permeability in the greater and lesser curvature of the aortic arch. In apoE
      null mice, the lesser curvature of the aortic arch develops lesions before the
      greater curvature. We found a significant and sustained decrease (59%) in IEL
      permeability in the lesser curvature of the aortic arch compared with the greater
      curvature. These data suggest that atherogenesis involves the pathological
      remodeling of the IEL, not the endothelium before lesion development. This
      remodeling may be attributable to local responses of the endothelium and smooth
      muscle cells to hyperlipidemia.

PMID- 16100043
TI  - Reduced wall compliance suppresses Akt-dependent apoptosis protection stimulated
      by pulse perfusion.
AB  - Reduced arterial compliance and increased pulse pressure are common and major
      risk factors for cardiovascular disease. Here, we reveal a novel mechanism
      whereby loss of wall distensibility blunts endothelial cell protection to oxidant
      stress-induced apoptosis. Bovine aortic endothelial cells cultured in compliant
      or stiff silastic tubes were pulse perfused by arterial pressure/flow waveforms
      generated by a servo-pump. Pulse perfusion induced time-dependent Akt activation
      peaking >6-fold after 2 hours in compliant tubes and a similar time course but
      half the magnitude in stiff tubes. This was accompanied by quantitatively similar
      disparities in phosphoinositide-3 kinase activation and in Akt-stimulated
      suppressors of apoptosis: glycogen synthase kinase-3beta, forkhead, and Bad.
      Cells perfused in compliant tubes had twice the protection against H2O2
      stimulated apoptosis than those in stiffer tubes. This protection was lost by
      pretreatment with an Akt inhibitor and restored in cells transfected with
      myristoylated Akt yet perfused in stiff tubes. Shear and stretch Akt signaling
      coupled to different upstream pathways as inhibition of vascular endothelial
      growth factor receptor 2 (VEGF2R) or disruption of caveolae blocked steady and
      pulse flow-mediated activation, yet did not suppress phosphorylated Akt induced
      by pulse perfusion in compliant tubes (concomitant stretch). Unlike Akt, reactive
      oxygen species, activated nuclear factor kappaB, and suppression of H2O2
      stimulated c-Jun-N-terminal kinase activity were similar in pulse-perfused
      compliant and stiff tubes. Thus, cyclic endothelial cell stretch by pulse
      perfusion enhances Akt-dependent antiapoptosis above that induced by steady or
      phasic shear stress and, unlike the latter, signals via a VEGF2R/caveolae
      independent pathway. Enhancing this stretch pathway may prove useful for
      improving endothelial function in stiff arteries.

PMID- 16100044
TI  - Thyroid hormone targets matrix Gla protein gene associated with vascular smooth
      muscle calcification.
AB  - Thyroid hormones have marked cardiovascular effects in vivo. However, their
      direct effects on vascular smooth muscle cells have been unclear. Because thyroid
      hormones play critical roles in bone remodeling, we hypothesized that they are
      also associated with vascular smooth muscle calcification, one of the
      pathological features of vascular sclerosis. To test this hypothesis, we examined
      the effects of 3',3,5-triiodo-L-thyronine (T3) on the expression of calcification
      associated genes in rat aortic smooth muscle cells (RAOSMCs). Quantitative RT
      PCRs revealed that a physiological concentration of T3 (15 pmol/L free T3)
      increased mRNA level of matrix Gla protein (MGP), which acts as a potent
      inhibitor of vascular calcification in vivo, by 3-fold in RAOSMCs, as well as in
      cultured human coronary artery smooth muscle cells. In RAOSMCs transiently
      transfected with a luciferase reporter gene driven by the MGP promoter, T3
      significantly stimulated luciferase activity. In addition, RNA interference
      against thyroid hormone receptor-alpha gene diminished the effect of T3 on MGP
      expression. Aortic smooth muscle tissues from methimazole-induced hypothyroid
      rats (400 mg/L drinking water; 4 weeks) also showed a 68% decrease in the MGP
      mRNA level, as well as a 33% increase in calcium content compared with that from
      the control euthyroid animals, whereas hyperthyroidism (0.2 mg T3/kg IP; 10 days)
      upregulated MGP mRNA by 4.5-fold and reduced calcium content by 11%. Our findings
      suggest that a physiological concentration of thyroid hormone directly
      facilitates MGP gene expression in smooth muscle cells via thyroid hormone
      nuclear receptors, leading to prevention of vascular calcification in vivo.

PMID- 16100045
TI  - Asymmetric dimethylarginine and the risk of cardiovascular events and death in
      patients with coronary artery disease: results from the AtheroGene Study.
AB  - As a competitive inhibitor of endothelial nitric oxide synthase, asymmetric
      dimethylarginine (ADMA) has been related to atherosclerotic disease. Little is
      known about the prognostic impact of baseline ADMA determination. In a
      prospective cohort of 1908 patients with coronary artery disease, we assessed
      baseline serum concentration of ADMA in 1874 consecutive patients with coronary
      artery disease. One hundred fourteen individuals developed the primary end point
      of death from cardiovascular causes or nonfatal myocardial infarction during a
      mean follow-up of 2.6+/-1.2 years. Median concentrations of ADMA levels were
      higher among individuals who subsequently developed the primary end point than
      among those who did not (0.70 versus 0.63 micromol/L; P<0.001). The risk of
      future cardiovascular event was associated with increasing thirds of baseline
      ADMA (P for trend, <0.001) such that individuals in the highest third at entry
      had a hazard ratio 2.48 times higher than those in the lowest third (95%
      confidence interval, 1.52 to 4.06; P<0.001). This relationship remained nearly
      unchanged after adjustment for most potential confounders. Prediction models that
      simultaneously incorporated ADMA, B-type natriuretic peptide, C-reactive protein,
      and creatinine in addition to traditional risk factors revealed B-type
      natriuretic peptide (hazard ratio, 1.96; 95% confidence interval, 1.3 to 3.0;
      P=0.002) and ADMA (hazard ratio, 1.90; 95% confidence interval, 1.3 to 2.8;
      P=0.001) as the strongest risk predictors. High levels of baseline ADMA
      independently predict future cardiovascular risk. ADMA has prognostic value
      beyond traditional risk factors and novel biomarkers and might guide therapeutic
      strategies.

PMID- 16100046
TI  - Oral small peptides render HDL antiinflammatory in mice and monkeys and reduce
      atherosclerosis in ApoE null mice.
AB  - A peptide containing only 4 amino acid residues (KRES) that is too small to form
      an amphipathic helix, reduced lipoprotein lipid hydroperoxides (LOOH), increased
      paraoxonase activity, increased plasma HDL-cholesterol levels, rendered HDL
      antiinflammatory, and reduced atherosclerosis in apoE null mice. KRES was orally
      effective when synthesized from either L or D-amino acids suggesting that peptide
      protein interactions were not required. Remarkably, changing the order of 2 amino
      acids (from KRES to KERS) resulted in the loss of all biologic activity.
      Solubility in ethyl acetate and interaction with lipids, as determined by
      differential scanning calorimetry, indicated significant differences between KRES
      and KERS. Negative stain electron microscopy showed that KRES formed organized
      peptide-lipid structures whereas KERS did not. Another tetrapeptide FREL shared
      many of the physical-chemical properties of KRES and was biologically active in
      mice and monkeys when synthesized from either L- or D-amino acids. After oral
      administration KRES and FREL were found associated with HDL whereas KERS was not.
      We conclude that the ability of peptides to interact with lipids, remove LOOH and
      activate antioxidant enzymes associated with HDL determines their
      antiinflammatory and antiatherogenic properties regardless of their ability to
      form amphipathic helixes.

PMID- 16100047
TI  - Expression and phosphorylation of the na-pump regulatory subunit phospholemman in
      heart failure.
AB  - Intracellular [Na] is approximately 3 mmol/L higher in heart failure (HF; in our
      arrhythmogenic rabbit model), and this can profoundly affect cardiac Ca and
      contractile function via Na/Ca exchange and Na/H exchange. Na/K-ATPase is the
      primary mechanism of Na extrusion. We examine here in HF rabbits (and human
      hearts) expression of Na/K-ATPase isoforms and phospholemman (PLM), a putative
      Na/K-ATPase regulatory subunit that inhibits pump function and is a major cardiac
      phosphorylation target. Na/K-ATPase alpha1- and alpha2-isoforms were reduced in
      HF in rabbit ventricular homogenates (by 24%) and isolated myocytes (by 30% and
      17%), whereas alpha3 was increased (50%) in homogenates and decreased (52%) in
      myocytes (P<0.05). Homogenate Na/K-ATPase activity in left ventricle was also
      decreased in HF. However, we showed previously that Na/K-ATPase characteristics
      in intact ventricular myocytes were unaltered in HF. To reconcile these findings,
      we assessed PLM expression, phosphorylation, and association with Na/K-ATPase.
      PLM coimmunoprecipitated with Na/K-ATPase alpha1 and alpha2 in control and HF
      rabbit myocytes. PLM expression was reduced in HF by 42% in isolated rabbit left
      ventricular (LV) myocytes, by 48% in rabbit LV homogenates, and by 24% in human
      LV homogenate. The fraction of PLM phosphorylated at Ser-68 was increased
      dramatically in HF. Our results are consistent with a role for PLM analogous to
      that of phospholamban for SR Ca-ATPase (SERCA): inhibition of Na/K-ATPase
      function that is relieved on PLM phosphorylation. So reduced Na/K-ATPase
      expression in HF may be functionally offset by lower inhibition by PLM (because
      of reduced PLM expression and higher PLM phosphorylation).

PMID- 16100048
TI  - Impairment of diazoxide-induced formation of reactive oxygen species and loss of
      cardioprotection in connexin 43 deficient mice.
AB  - Protection by ischemic preconditioning is lost in cardiomyocytes and hearts of
      heterozygous connexin 43 deficient (Cx43+/-) mice. Because connexin 43 (Cx43) is
      localized in cardiomyocyte mitochondria and mitochondrial Cx43 content is
      increased with ischemic preconditioning, we now tried to identify a functional
      defect at the level of the mitochondria in Cx43+/- mice by use of diazoxide and
      menadione. Diazoxide stimulates the mitochondrial formation of reactive oxygen
      species (ROS) and menadione generates superoxide at multiple intracellular sites;
      both substances elicit cardioprotection through increased ROS formation. ROS
      formation in response to the potassium ionophore valinomycin was also measured
      for comparison. Menadione (2 micromol/L) and valinomycin (10 nmol/L) induced
      similar ROS formation in wild-type (WT) and Cx43+/- cardiomyocytes. In contrast,
      diazoxide (200 micromol/L) increased ROS formation by 43+/-10% versus vehicle in
      WT, but only by 18+/-4% in Cx43+/- cardiomyoctes (P<0.05). Two hour-simulated
      ischemia and oxygenated, hypo-osmolar reperfusion reduced viability as compared
      with normoxia (WT: 7+/-1% versus 39+/-2%, (Cx43+/-): 8+/-1% versus 40+/-3%,
      P<0.01). Although menadione protected WT and Cx43+/- cardiomyocytes, diazoxide
      increased viability (17+/-2%, P<0.01) in WT, but not in Cx43+/- (9+/-1%).
      Menadione (37 microg/kg i.v.) before 30 minutes coronary occlusion and 2 hour
      reperfusion reduced infarct size in WT and Cx43+/- mice (24+/-4% versus 24+/-5%).
      In contrast, diazoxide (5 mg/kg i.v.) reduced infarct size in WT (35+/-4% versus
      55+/-3% of area at risk, P<0.01), but not in Cx43+/- mice (56+/-2% versus 54+/
      3%). Cardiomyocytes of Cx43+/- mice have a specific functional deficit in ROS
      formation in response to diazoxide and accordingly less protection.

PMID- 16100049
TI  - Calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion
      contributes to cell death after myocardial ischemia.
AB  - Na+ overload and secondary Ca2+ influx via Na+/Ca2+ exchanger are key mechanisms
      in cardiomyocyte contracture and necrosis during reperfusion. Impaired Na+/K+
      ATPase activity contributes to Na+ overload, but the mechanism has not been
      established. Because Na+/K+-ATPase is connected to the cytoskeleton protein
      fodrin through ankyrin, which are substrates of calpains, we tested the
      hypothesis that calpain mediates Na+/K+-ATPase impairment in reperfused
      cardiomyocytes. In isolated rat hearts reperfused for 5 minutes after 60 minutes
      of ischemia, Na+/K+-ATPase activity was reduced by 80%, in parallel with loss of
      alpha-fodrin and ankyrin-B and detachment of alpha1 and alpha2 subunits of Na+/K+
      ATPase from the membrane-cytoskeleton complex. Calpain inhibition with MDL-7943
      during reperfusion prevented the loss of these proteins, increased Na+/K+-ATPase
      activity, attenuated lactate dehydrogenase release, and improved contractile
      recovery, and these beneficial effects of MDL-7943 were reverted by ouabain. The
      impairment of Na+/K+-ATPase was not a mere consequence of cell death because it
      was not altered in hearts in which contracture and cell death had been prevented
      by contractile blockade with 2,3-butanedione monoxime. In these hearts,
      concomitant calpain inhibition preserved Na+/K+-ATPase content and function and
      attenuated cell death occurring on withdrawal of 2,3-butanedione monoxime. In
      vitro assay showed no detectable degradation of Na+/K+-ATPase subunits after 10
      minutes of incubation with activated calpain. Thus, we conclude that calpain
      activation contributes to the impairment of Na+/K+-ATPase during early
      reperfusion and that this effect is mainly mediated by degradation of the
      anchorage of Na+/K+-ATPase to the membrane cytoskeleton.

PMID- 16100050
TI  - Crosstalk of beta-adrenergic receptor subtypes through Gi blunts beta-adrenergic
      stimulation of L-type Ca2+ channels in canine heart failure.
AB  - The mechanisms underlying the blunted contractile response to beta-adrenergic
      receptor (beta-AR) stimulation in heart failure (HF) are incompletely understood,
      especially with regard to beta-AR subtype-specific regulation of L-type Ca2+
      channels. We evaluated the impact of HF induced by pacing tachycardia on beta-AR
      regulation of L-type Ca2+ channels in a canine model. To evaluate changes in the
      relative subcellular distribution of beta-AR subtypes, left ventricular membranes
      enriched in surface sarcolemma and T-tubular sarcolemma were prepared.
      Radioligand binding using [(125)I]cyanopindolol revealed that HF resulted in a
      comparable decrease in the density of beta1-ARs in both surface and T-tubule
      sarcolemma (55+/-4%, n=7, P<0.001; and 45+/-10%, n=7, P<0.01, respectively), but
      no significant change in beta2-AR density was observed. Whole-cell patch clamp
      studies demonstrated a markedly blunted increase in I(Ca,L) in response to
      saturating concentrations of the nonselective beta-AR agonist isoproterenol (0.1
      micromol/L) in failing myocytes compared with control (129+/-20%, n=11, versus
      332+/-35%, n=7; P<0.001). Experiments testing beta1-AR- and beta2-AR-selective
      stimulation showed that the major component of the blunted response to
      nonselective beta-AR stimulation in HF was caused by beta2-AR activation,
      resulting in a pertussis toxin-sensitive, Gi-mediated inhibition of the beta1-AR
      induced increase in I(Ca,L). In conclusion, canine HF results in the following:
      (1) a uniform reduction in beta1-AR density in surface and T-tubule membrane
      fractions without a change in beta2-AR density; and (2) the emergence of distinct
      Gi-coupling to beta2-ARs resulting in accentuated antagonism of beta1-AR-mediated
      stimulation of I(Ca,L). These results have implications for optimizing the use of
      beta-AR drugs in HF.

PMID- 16100051
TI  - Cell-signaling evidence for adenosine stimulation of coronary smooth muscle
      proliferation via the A1 adenosine receptor.
AB  - For decades, it has been thought that adenosine is exclusively antimitogenic on
      vascular smooth muscles via the A2-type adenosine receptor. Recently, we have
      demonstrated that adenosine stimulates proliferation of porcine coronary artery
      smooth muscle cells (CASMC) through the A1 adenosine receptor. However, the cell
      signaling mechanisms underlying A1 receptor-mediated CASMC proliferation in
      response to adenosine have not been defined. Here, we show that in cultured
      CASMC, adenosine stimulates phosphorylation of extracellular signal-regulated
      kinase (ERK), Jun N-terminal kinase (JNK), and AKT in a concentration- and time
      dependent manner. This effect is fully mimicked by NECA (nonselective agonist),
      largely mimicked by CCPA (A1-selective agonist), weakly mimicked by 2-Cl-IB-MECA
      (A3-selective agonist), but not by CGS21680 (A2A-selective agonist), indicating
      that adenosine signals strongly via the A1 receptor to these mitogenic signaling
      pathways. This interpretation is supported by the finding that adenosine- and
      CCPA-induced phosphorylation of ERK, JNK, and AKT are inhibited by pertussis
      toxin (inactivator of Gi proteins) and by DPCPX (A1-selective antagonist), but
      not by SCH58261, MRS1706, and VUF5574 (A2A-, A2B-, and A3-selective antagonists,
      respectively). In addition, adenosine- and CCPA-induced phosphorylation of ERK,
      JNK, and AKT is inhibited, respectively, by U0126, PD98059 (mitogen-activated
      protein kinase kinase inhibitors), SP600125 (JNK kinase inhibitor), and
      wortmannin (phosphatidylinositol 3-kinase inhibitor). Furthermore, these kinase
      inhibitors abolish or diminish adenosine- and CCPA-induced increases in the rate
      of cellular DNA synthesis, bromodeoxyuridine incorporation, protein synthesis,
      and cell number. We conclude that adenosine activates the ERK, JNK, and
      phosphatidylinositol 3-kinase/AKT pathways primarily through the A1 receptor,
      leading to CASMC mitogenesis.

PMID- 16100052
TI  - Exclusion of the swine leukocyte antigens as candidate region and reduction of
      the position interval for the Sus scrofa chromosome 7 QTL affecting growth and
      fatness.
AB  - Pig chromosome 7 (SSC 7) has been shown to be rich in QTL affecting performance
      and quality traits. Most studies mapped the QTL close to the swine leukocyte
      antigens (SLA), which has a large effect on adaptability and natural selection.
      Previous comparative mapping studies suggested that the 15-cM region limited by
      markers LRA1 (mapped at 55 cM) and S0102 (mapped at 70 cM) contains hundreds of
      genes. To decrease the number of candidate genes, we improved the mapping
      resolution with a genetic chromosome dissection through a backcross recombinant
      progeny test program between Meishan (MS) and European (EU; i.e., Large White or
      Landrace) breeds. Three first-generation backcross--(EU x MS) x EU--and two
      second-generation backcross--([EU x MS] x EU) x EU--sires carrying a
      recombination in the QTL mapping interval were progeny-tested (i.e., measured for
      a total of 44 growth, fatness, carcass and meat quality traits). Progeny family
      size varied from 29 to 119 pigs. Animals were genotyped for markers covering the
      region of interest. Progeny-test results allowed the QTL interval to be decreased
      from 15 to 20 cM down to 10 cM, and even less than 6 cM if we assumed that the EU
      pigs used in this study share only one QTL allele. Except for a putative QTL
      affecting some carcass composition traits, the SLA is excluded as a candidate
      region, suggesting that it might be possible to apply a marker-assisted selection
      strategy for this QTL, while controlling SLA allele diversity. The strong QTL
      effects remaining in animals with only 12.5% (issued from first-generation
      backcross boars) and 6.25% (issued from second-generation back-cross boars)
      Meishan genetic background shows that epistatic interactions are likely to be
      limited. Finally, the QTL does not have strong effects on meat quality traits.

PMID- 16100053
TI  - A directed search in the region of GDF8 for quantitative trait loci affecting
      carcass traits in Texel sheep.
AB  - A directed search for QTL affecting carcass traits was carried out in the region
      of growth differentiation factor 8 (GDF8, also known as myostatin) on ovine
      chromosome 2 in seven Texel-sired half-sib families totaling 927 progeny. Weights
      were recorded at birth, weaning, ultrasound scanning, and slaughter. Ultrasonic
      measures of LM cross-sectional dimensions and s.c. fat above the LM were made,
      with the same measurements made on the LM after slaughter. Following slaughter,
      linear measurements of carcass length and width were made on all carcasses, and
      legs and loins from 540 lambs were dissected. Genotyping was carried out using
      eight microsatellite markers from FCB128 to RM356 on OAR 2 and analyzed using
      Haley-Knott regression. There was no evidence for QTL for growth rates or linear
      carcass traits. There was some evidence for QTL affecting LM dimensions
      segregating in some sire families, although it was not consistent between
      ultrasound and carcass measures of the same traits. There was strong and
      consistent evidence for a QTL affecting muscle and fat traits in the leg that
      mapped between markers BM81124 and BULGE20 for the four sires that were
      heterozygous in this region, but not for the three sires that were homozygous.
      The size of the effect varied across the four sires, ranging from 0.5 to 0.9 of
      an adjusted SD for weight-adjusted leg muscle traits, and ranging from 0.6 to 1.2
      of an adjusted SD for weight-adjusted leg fat traits. The clearest effect shown
      was for multivariate analysis combining all leg muscle and fat traits analyzed
      across sires, where the -log(10) probability was 14. Animals carrying the
      favorable haplotype had 3.3% more muscle and 9.9% less fat in the leg relative to
      animals carrying other haplotypes. There was evidence for a second peak in the
      region of marker TEXAN2 for one sire group. It seems that a QTL affecting muscle
      and fat traits exists within the New Zealand Texel population, and it maps to the
      region of GDF8 on OAR2.

PMID- 16100054
TI  - A new single nucleotide polymorphism in CAPN1 extends the current tenderness
      marker test to include cattle of Bos indicus, Bos taurus, and crossbred descent.
AB  - The three objectives of this study were to 1) test for the existence of beef
      tenderness markers in the CAPN1 gene segregating in Brahman cattle; 2) test
      existing CAPN1 tenderness markers in indicus-influenced crossbred cattle; and 3)
      produce a revised marker system for use in cattle of all subspecies backgrounds.
      Previously, two SNP in the CAPN1 gene have been described that could be used to
      guide selection in Bos taurus cattle (designated Markers 316 and 530), but
      neither marker segregates at high frequency in Brahman cattle. In this study, we
      examined three additional SNP in CAPN1 to determine whether variation in this
      gene could be associated with tenderness in a large, multisire American Brahman
      population. One marker (termed 4751) was associated with shear force on
      postmortem d 7 (P < 0.01), 14 (P = 0.015), and 21 (P < 0.001) in this population,
      demonstrating that genetic variation important for tenderness segregates in Bos
      indicus cattle at or near CAPN1. Marker 4751 also was associated with shear force
      (P < 0.01) in the same large, multisire population of cattle of strictly Bos
      taurus descent that was used to develop the previously reported SNP (referred to
      as the Germplasm Evaluation [GPE] Cycle 7 population), indicating the possibility
      that one marker could have wide applicability in cattle of all subspecies
      backgrounds. To test this hypothesis, Marker 4751 was tested in a third large,
      multisire cattle population of crossbred subspecies descent (including sire
      breeds of Brangus, Beefmaster, Bonsmara, Romosinuano, Hereford, and Angus
      referred to as the GPE Cycle 8 population). The highly significant association of
      Marker 4751 with shear force in this population (P < 0.001) confirms the
      usefulness of Marker 4751 in cattle of all subspecies backgrounds, including Bos
      taurus, Bos indicus, and crossbred descent. This wide applicability adds
      substantial value over previously released Markers 316 and 530. However, Marker
      316, which had previously been shown to be associated with tenderness in the GPE
      Cycle 7 population, also was highly associated with shear force in the GPE Cycle
      8 animals (P < 0.001). Thus, Marker 316 may continue to be useful in a variety of
      populations with a high percentage of Bos taurus backgrounds. An optimal marker
      strategy for CAPN1 in many cases will be to use both Markers 316 and 4751.

PMID- 16100055
TI  - Association of single nucleotide polymorphisms in the leptin gene with carcass
      and meat quality traits of beef cattle.
AB  - Studies with different populations are required to properly characterize the
      robustness of associations of polymorphisms in candidate genes with economically
      important traits across beef cattle populations before this sort of genetic
      information can be used efficiently in breeding and management decisions. The
      objective of this study was to evaluate the association of previously reported
      SNP in the bovine leptin gene with carcass and meat quality traits from a large
      sample of crossbred beef cattle. Five SNP (UASMS1, UASMS2, UASMS3, E2JW, and
      E2FB) were genotyped on 1,111 crossbred bulls, heifers, and steers. The measured
      traits included fat, lean, and bone yield (%) by partial rib dissection, grade
      fat, LM area, HCW, quality grade, LM i.m. fat, and tenderness evaluation of LM
      and semitendinosus muscle. Only four SNP were analyzed (UASMS1, UASMS2, E2JW, and
      E2FB), because UASMS1 and UASMS3 were completely linked. A uni-variate mixed
      inheritance animal model was used to evaluate the association of either genotypes
      or haplo-types with the traits. The two leptin exon 2 SNP were associated with
      fat and lean yield and grade fat (E2JW, P < 0.01; E2FB, P < 0.05), and they
      interacted in their effect on LM tenderness (P < 0.01). The leptin promoter SNP
      were either not associated with any of the traits (UASMS2) or with fat yield only
      (UASMS1). Three haplotypes (TCAC, CCAT, TTAC) were at high frequency in the
      population (88%) and had similar effects on all the traits. Compared with the
      common haplotypes, one haplotype (CCTT) showed a significantly different effect
      on fat and lean yield and grade fat (P < 0.01), and one haplotype (TTTT) had a
      different effect on LM tenderness (P < 0.03). Therefore, important associations
      between SNP within the leptin gene with lean yield, fatness (fat yield and
      subcutaneous fat), and tenderness were detected. Results confirm some of the
      previously reported associations, but diverge with respect to others, showing
      that further efforts are required to validate some prospective associations.

PMID- 16100056
TI  - Genetic and economic evaluation of Japanese Black (Wagyu) cattle breeding
      schemes.
AB  - Deterministic simulation was used to evaluate 10 breeding schemes for genetic
      gain and profitability and in the context of maximizing returns from investment
      in Japanese Black cattle breeding. A breeding objective that integrated the cow
      calf and feedlot segments was considered. Ten breeding schemes that differed in
      the records available for use as selection criteria were defined. The schemes
      ranged from one that used carcass traits currently available to Japanese Black
      cattle breeders (Scheme 1) to one that also included linear measurements and male
      and female reproduction traits (Scheme 10). The latter scheme represented the
      highest level of performance recording. In all breeding schemes, sires were
      chosen from the proportion selected during the first selection stage (performance
      testing), modeling a two-stage selection process. The effect on genetic gain and
      profitability of varying test capacity and number of progeny per sire and of
      ultrasound scanning of live animals was examined for all breeding schemes.
      Breeding schemes that selected young bulls during performance testing based on
      additional individual traits and information on carcass traits from their
      relatives generated additional genetic gain and profitability. Increasing test
      capacity resulted in an increase in genetic gain in all schemes. Profitability
      was optimal in Scheme 2 (a scheme similar to Scheme 1, but selection of young
      bulls also was based on information on carcass traits from their relatives) to 10
      when 900 to 1,000 places were available for performance testing. Similarly, as
      the number of progeny used in the selection of sires increased, genetic gain
      first increased sharply and then gradually in all schemes. Profit was optimal
      across all breeding schemes when sires were selected based on information from
      150 to 200 progeny. Additional genetic gain and profitability were generated in
      each breeding scheme with ultrasound scanning of live animals for carcass traits.
      Ultrasound scanning of live animals was more important than the addition of any
      other traits in the selection criteria. These results may be used to provide
      guidance to Japanese Black cattle breeders.

PMID- 16100057
TI  - Genetic parameters for stayability, stayability at calving, and stayability at
      weaning to specified ages for Hereford cows.
AB  - Genetic parameters for stayability to six ages (ST1, . . ., ST6), for five
      measures of stayability to calving (SC2, . . ., SC6), and for five measures of
      stayability to weaning (SW2, . . ., SW6), were estimated using records of 2,019
      Hereford cows collected from 1964 to 1979 from a selection experiment with a
      control line and three lines selected for weaning weight, yearling weight, and an
      index of yearling weight and muscle score. The model included birth year of the
      cow as a fixed effect and the cow's sire as a random effect. Analyses were
      performed with 1) a generalized linear mixed model for binary data using a probit
      link with a penalized quasi-likelihood function, and 2) with a linear mixed model
      using REML. Genetic trends were estimated by regressing weighted means of
      estimated transmitting abilities (ETA) of sires by birth year of their daughters
      on birth year. Environmental trends were estimated by regressing solutions for
      year of birth on birth year. Estimates of heritability (SE) for ST were between
      0.09 (0.08) and 0.30 (0.14) for threshold model and between 0.05 (0.04) and 0.19
      (0.09) for linear model. Estimates of heritability from linear model analyses
      transformed to an underlying normal scale were between 0.09 and 0.35. Estimates
      of heritability (SE) for SC were between 0.29 (0.10) and 0.39 (0.11) and between
      0.18 (0.09) and 0.25 (0.08) with threshold and linear models. Estimates of
      heritability transformed to an underlying normal scale were between 0.30 and
      0.40. Estimates of heritability (SE) for SW were between 0.21 (0.14) and 0.47
      (0.19) and between 0.12 (0.08) and 0.26 (0.12) with threshold and linear models,
      respectively. Estimates of heritability transformed to an underlying normal scale
      were between 0.21 and 0.50. Estimates of genetic and environmental trends for all
      lines were nearly zero for all traits. Correlations between ETA of sires for
      stayability to specific ages, for stayability to calving, and for stayability to
      weaning with threshold and linear models ranged from 0.09 to 0.82, from 0.68 to
      0.90, and from 0.67 to 0.87, respectively. Selection for stayability would be
      possible in a breeding program and could be relatively effective as a result of
      the moderate estimates of heritability, which would allow selection of sires
      whose daughters are more likely to remain longer in the herd. Selection for
      weaning and yearling weights resulted in little correlated response for any of
      the measures of stayability.

PMID- 16100058
TI  - Relationship between profitability and type traits and derivation of economic
      values for reproduction and survival traits in Chianina beef cows.
AB  - The objectives of this study were 1) to propose a profit function for Italian
      Chianina beef cattle; 2) to derive economic values for some biological variables
      in beef cows, specifically, production expressed as the number of calves born
      alive per year (NACY), age at the insemination that resulted in the birth of the
      first calf (FI), and length of productive life (LPL); and 3) to investigate the
      relationship between the phenotypic profit function and type traits as early
      predictors of profitability in the Chianina beef cattle population. The average
      profit was 196 Euros/(cow.yr) for the length of productive life (LPL) and was
      obtained as the difference between the average income of 1,375 Euros/(cow.yr) for
      LPL and costs of 1,178 Euros/(cow.yr) of LPL. The mean LPL was equal to 5.97 yr,
      so the average total phenotypic profit per cow on a lifetime basis was 1,175
      Euros. A normative approach was used to derive the economic weights for the
      biological variables. The most important trait was the number of calves born
      alive (+4.03.cow(-1).yr(-1) and +24.06 Euros/cow). An increase of 1 d in LPL was
      associated with an increase of +0.19 Euros/(cow.yr) and +1.65 Euros/cow on a
      lifetime basis. Increasing FI by 1 d decreased profit by 0.42 Euros/(cow.yr) and
      2.51 Euros/cow. Phenotypic profit per cow had a heritability of 0.29.
      Heritabilities for eight muscularity traits ranged from 0.16 to 0.23, and for the
      seven body size traits between 0.21 and 0.30. The conformation trait final score
      can be used as an early predictor of profitability. The sale price of the animal
      and differences in the revenue and costs of offspring due to muscularity should
      be included in a future profit function.

PMID- 16100059
TI  - Study of codes of disposal at different parities of Large White sows using a
      linear censored model.
AB  - To study the genetic relationship between three grouped reasons for sow removal
      (SR) in consecutive parities, accounting for censoring, 13,838 records from Large
      White sows were analyzed. Data were from seven pure-line farms having, on
      average, 5.9% unknown SR. Three traits were subjectively defined, each
      corresponding to a classification of SR (reproductive [RR], nonreproductive [RN],
      and others [RO]). Records for each trait could take one of five categories,
      according to parity at removal (0 to 4 or later). A multivariate linear censored
      model was implemented. The model to estimate (co)variance components and
      parameters included the effects of year-season, region, contemporary group, and
      additive genetic effects. The most common SR was related to reproduction (48.5%).
      Diseases of different origin and cause, old age/parity, and sow death or loss
      accounted for about 18, 7, and 4% of total culls, respectively. Estimates of
      variance components showed heterogeneity of additive genetic and residual
      variances for the three traits. Estimates of heritability were 0.18, 0.13, and
      0.15 for RR, RN, and RO, respectively. Genetic correlations between removal codes
      were high (> or =0.90). Results suggest sizeable additive genetic variances exist
      for parity at removal and different codes of removal. Different SR reasons seem
      to operate similarly or as a closely related genetic trait associated with
      fitness. In particular, RN and RO seem to be genetically indistinguishable. Data
      structure, definition, and volume are major limitations in studies of sow
      survival. A multiple-trait censored model is preferred to evaluate reasons of sow
      disposal. Grouped removal causes seem to be strongly genetically correlated but
      with heterogeneous variances, suggesting that combining all removal causes and
      treating the trait as parity at disposal is an alternative approach.

PMID- 16100060
TI  - Genetic parameter estimates of meat quality traits in Duroc pigs selected for
      average daily gain, longissimus muscle area, backfat thickness, and intramuscular
      fat content.
AB  - Using a multitrait animal model BLUP, selection was conducted over seven
      generations for growth rate (ADG), real-time ultrasound LM area (LMA), backfat
      thickness (BF), and intramuscular fat content (IMF) to develop a new line of
      purebred Duroc pigs with enhanced meat production and meat quality. This
      selection experiment examined 543 slaughtered pigs (394 barrows and 153 gilts)
      from the first to the seventh generation for meat quality traits. Further,
      electric impedance and collagen content of loin meat were measured from the
      fourth to sixth generation. The present study was intended to estimate genetic
      parameters of the correlated traits of tenderness (TEND), meat color (pork color
      standard: PCS; lightness = L*), drip loss (DL), cooking loss (CL), pH (PH),
      electric impedance (IMP), and collagen (COL) of the LM, and the genetic trends of
      these traits. Respective heritability estimates for IMF, TEND, DL, CL, PCS, L*,
      PH, IMP, and COL were 0.39, 0.45, 0.14, 0.09, 0.18, 0.16, 0.07, 0.22, and 0.23.
      Genetic correlations of IMF with ADG and BF were low and positive, but low and
      negative with LMA. Tenderness was correlated negatively with ADG (-0.44) and BF (
      0.59), but positively correlated with LMA (0.32). The genetic correlation between
      LMA and DL was positive and high (0.64). The genetic correlations of TEND with
      IMF and COL were low (-0.09 and 0.26, respectively), but a moderate genetic
      correlation (0.43) between COL and IMF was estimated, suggesting related
      increases of IMF and connective tissue. Genetic correlations among meat quality
      traits suggested that when IMF increases, the water holding capacity improves.
      Genetic trends of meat quality traits showed increased IMF and lighter meat
      color.

PMID- 16100061
TI  - Porcine preadipocyte proliferation and differentiation: a role for leptin?
AB  - The present study was designed to determine whether porcine leptin can alter the
      proliferation and differentiation of the porcine preadipocyte. The stromal
      vascular cell fraction of neonatal pig s.c. adipose tissue was isolated by
      collagenase digestion, filtration, and subsequent centrifugation. For
      differentiation studies, cells were seeded on six-well tissue culture plates and
      proliferated to confluency in 10% (vol/vol) fetal bovine serum (FBS) in
      Dulbecco's modified Eagle medium/F12 (DMEM/F12; 50:50). Cultures were
      differentiated using 2.5% pig serum (vol/vol) and recombinant porcine leptin at
      concentrations of 0 to 1,000 ng/mL alone or in combination with porcine insulin
      (100 nM), dexamethasone (1 microM), or IGF-1 (250 ng/mL). After 7 d of lipid
      filling, cultures were harvested for analysis of sn-glycerol 3 phosphate
      dehydrogenase (GPDH) and lipoprotein lipase (LPL). The GPDH and LPL activities
      are measures of preadipocyte differentiation. Data were corrected for protein
      content of the cultures. For proliferation experiments, 24 h after seeding cells
      with 10% FBS in DMEM/F12 in 25-cm2 tissue culture flasks, cells were switched to
      5% FBS and supplemented with 0 to 1,000 ng of porcine leptin or 1,000 ng of
      murine leptin. Cell proliferation was measured by 3H-thymidine incorporation in
      preconfluent cultures over 24 h on d 4 of culture. At confluency, cells were
      switched to a medium to promote differentiation and lipid filling (2.5% pig
      serum, 100 nM insulin, 1 microM dexamethasone) for 7 d. Cells were harvested from
      the flasks and adipocytes were separated from stromal cells by Percoll gradient
      centrifugation. In a series of experiments, leptin alone or in combination with
      insulin, dexamethasone, or IGF-I did not affect differentiation as measured by
      the activity of GPDH and LPL. Leptin at any concentration did not inhibit
      differentiation induced by insulin, dexamethasone, or IGF-I; however, leptin at
      1,000 ng/mL stimulated a 30% increase in preadipocyte proliferation (P = 0.007; n
      = 6) and a 27% increase in stromal cell proliferation (P < 0.001; n = 6). These
      results indicate that, at most, porcine leptin may contribute to the recruitment
      of new adipocytes within the adipose tissue.

PMID- 16100062
TI  - Differentially transcribed genes in skeletal muscle of Duroc and Taoyuan pigs.
AB  - The objective of this study was to compare gene transcription profiles of LM
      between two pig breeds, Duroc and Taoyuan, which display dramatically different
      postnatal muscle growth. We isolated LM from neonatal pigs, and the Duroc muscle
      length and mass were greater (P < 0.01) than for Taoyuan pigs; however,
      insignificant differences in the muscle fiber area and the percentage of fiber
      types were found. A human high-density complementary DNA (cDNA) microarray
      consisting of 9,182 probes was used to compare gene transcription profiles of LM
      between the two breeds. The results showed that the transcription level of 73
      genes and 44 genes in Duroc LM were upregulated and down-regulated by at least
      1.75-fold (P < 0.05) compared with Taoyuan, respectively. The strongly
      upregulated genes in Duroc pigs included those encoding the complex of
      myofibrillar proteins (e.g., myosin light and heavy chains, and troponin),
      ribosomal proteins, transcription regulatory proteins (e.g., skeletal muscle LIM
      protein 1 [SLIM1] and high-mobility group proteins), and energy metabolic enzymes
      (e.g., electron-transferring flavo-protein dehydrogenase, NADH dehydrogenase,
      malate dehydrogenase, and ATP synthases). The highly transcribed genes that
      encode energy metabolic enzymes indicate a more glycolytic metabolism in Duroc
      LM, thereby favoring carbohydrates rather than lipids for use as energy
      substrates in this tissue. The over-transcribed genes that encode skeletal muscle
      predominant proteins or transcription regulators that control myogenesis and/or
      muscle growth suggest a general mechanism for the observed higher rate of
      postnatal muscle growth in Duroc pigs. The transcription of one such gene, SLIM1,
      was more highly transcribed (P < 0.01) in Duroc LM at birth and at postnatal d 7
      than in Taoyuan. The transcription of SLIM1 increased (P < 0.05) in Duroc LM from
      neonate through 7 d of age, whereas its transcription remained essentially
      constant in Taoyuan during this period. These results suggest that SLIM1 may be
      useful for the development of markers associated with the postnatal muscle growth
      of pigs.

PMID- 16100063
TI  - Breed and age affect baseline immune traits, cortisol, and performance in growing
      pigs.
AB  - It was hypothesized in these studies that differences would exist in baseline
      immune and performance measures among different breeds of pigs, and that these
      differences would be affected by age of the pig. Baseline immune, plasma cortisol
      (CORT) concentrations, and performance measures were determined among Berkshire
      (n = 36), Duroc (n = 18), Meishan (n = 54), Landrace x Yorkshire (White X; n =
      36), and Yorkshire (n = 36) pigs at 4, 8, and 12 wk of age. All piglets were
      weaned at 17 to 21 d of age and moved to a common nursery environment. Total
      white blood cell (WBC), leukocyte differential, plasma CORT, immunoglobulin G
      (IgG) concentrations, natural killer cytotoxicity, neutrophil phagocytosis
      (PHAGO), and chemotaxis (CHTX) were evaluated. At all ages, plasma CORT was
      greatest in Meishan pigs, and least in Yorkshires (P < 0.05). Plasma IgG
      increased with age for all breeds (age: P < 0.01; breed x age: P < 0.005), except
      that in Meishans, IgG decreased. Natural killer cytotoxicity was greatest (P <
      0.05) among Meishan pigs. There were breed x age interactions for neutrophil
      PHAGO (P < 0.001) and CHTX (P < 0.001). Overall, Yorkshire pigs showed the
      greatest (P < 0.05) percentage of PHAGO but the least (P < 0.05) CHTX. White X
      pigs had the greatest (P < 0.05) CHTX response. Berkshire pigs had the greatest
      (P < 0.001) numbers of neutrophils. At 12 wk of age, Meishan pigs had the least
      BW gain (P < 0.001), and Durocs had the greatest G:F (P < 0.001). There were no
      significant sex differences for immune (P > or = 0.15), performance (P > or =
      0.20), or CORT (P = 0.70) measures. Pig breed and age influenced both baseline
      immune measures and plasma CORT in growing pigs, suggesting that pig breed and
      age are important factors influencing the response to various stressors or
      infectious challenges.

PMID- 16100064
TI  - Isomer-specific regulation of differentiating pig preadipocytes by conjugated
      linoleic acids.
AB  - Conjugated linoleic acids are a group of geometric and positional isomers of
      linoleic acid that decrease body fat in growing animals by a poorly understood
      mechanism. The objective of this study was to investigate the isomer-specific
      effect of CLA on the proliferation and differentiation of pig preadipocytes in
      primary culture. The effect of CLA on preadipocyte proliferation was determined
      using cleavage of the tetrazolium salt, WST-1, as a marker for proliferation.
      Preadipocyte number was decreased in a dose-dependent fashion by trans-12,cis-10
      CLA (P < 0.05). No other fatty acid affected preadipocyte number. Differentiation
      was monitored on d 10 after induction morphologically, enzymatically, and by
      measuring the mRNA abundance of key adipogenic transcription factors. Both a
      crude CLA preparation containing a mixture of CLA isomers (CLA-mix) and the pure
      trans-10,cis-12 CLA isomer inhibited glycerol-3-phosphate dehydrogenase (GPDH)
      activity in a dose-dependent fashion, with trans-10,cis-12 CLA being more potent
      (P < 0.01) than the CLA-mix. Cis-9,trans-11 CLA failed to decrease GPDH activity;
      however, increasing concentrations of cis-9,trans-11 CLA tended to blunt the
      inhibitory effect of trans-10,cis-12 CLA on GPDH activity (P < 0.09), suggesting
      that cis-9,trans-11 CLA may antagonize the action of trans-10,cis-12 CLA in
      porcine adipocytes. Finally, the isomer-specific effect of CLA on adipogenic
      transcription factor gene expression was investigated. Trans-10,cis-12 CLA
      decreased expression of peroxisome proliferator-activated receptor gamma (PPAR
      gamma; P < 0.01) and sterol regulatory element-binding protein-1c (SREBP-1c; P <
      0.05) mRNA, while failing to alter the expression of CCAAT/enhancer binding
      protein alpha (C/EBPalpha) mRNA. Interestingly, both the CLA-mix and the trans
      10,cis-12 CLA isomer increased the mRNA abundance of chicken ovalbumin upstream
      promoter transcription factor 1 (COUP-TF; P < 0.002). No other fatty acid
      affected COUP-TF mRNA levels. Collectively these data support the concept that
      CLA decreases fat accretion in pigs, in part by inhibiting preadipocyte
      proliferation and differentiation, with trans-10,cis-12 CLA being an active
      isomer eliciting these effects. Furthermore, trans-10,cis-12 CLA inhibits porcine
      preadipocyte differentiation by a mechanism that involves the down-regulation of
      PPARgamma and SREBP-1c mRNA. This mechanism is independent of changes in
      C/EBPalpha mRNA abundance and may involve COUP-TF.

PMID- 16100065
TI  - Introduction of bulls at different days postpartum on resumption of ovarian
      cycling activity in primiparous beef cows.
AB  - The objective of this study was to evaluate postpartum resumption of ovulatory
      cycles among primiparous, suckled beef cows that were exposed continuously to
      mature bulls beginning at various intervals after calving. We sought to determine
      whether cumulative distributions of proportions of cows resuming ovarian cycles
      and interval from the start of bull exposure to resumption of ovarian cycling
      activity differed among cows exposed continuously (BE) or not exposed (NE) to
      bulls beginning on d 15, 35, or 55 after calving. Angus x Hereford cows (n = 56)
      were assigned randomly to one of six treatments in a 2 (exposure type) x 3 (day
      exposed postpartum) factorial arrangement. Blood samples were collected from each
      cow starting on d -1, and every third day until the end of experiment. An
      increase in baseline progesterone concentrations that exceeded 1.0 ng/mL in three
      consecutive samples was used as evidence of resumption of ovarian cycling
      activity. More (P < 0.05) BE cows resumed cycling activity by the end of the
      experiment than NE cows. Proportions of cows resuming cycling activity did not
      differ (P = 0.30) among cows exposed to bulls on d 15, 35, or 55 postpartum.
      Proportions of BE cows that were exposed to bulls on d 15, 35, or 55 were greater
      for each 10-d interval (P < 0.05) than those for NE cows during the first 40 d
      after exposure. More (P < 0.05) BE cows exposed to bulls on d 55 resumed cycling
      activity by 30 d after exposure than BE cows exposed to bulls on either d 15 or
      35. Interval from calving to resumption of cycling activity was decreased (P <
      0.05) by the presence of bulls. Day of exposure did not affect (P = 0.21)
      interval from calving to resumption of cycling activity; however, interval from
      day of bull exposure to resumption of cycling activity decreased (P < 0.05)
      linearly as day of exposure to bulls after calving increased. We conclude that
      exposing primiparous beef cows to bulls decreased the postpartum anovulatory
      interval and increased the proportion of cows that exhibit resumption of ovarian
      cycling activity, independent of day of bull exposure. Furthermore, cows exposed
      to bulls at progressively later intervals postpartum seemed to respond more
      rapidly to the biostimulatory effect of bulls than when they were exposed earlier
      in the postpartum anestrous period.

PMID- 16100066
TI  - Testicular development of Zebu bulls after chronic treatment with a gonadotropin
      releasing hormone agonist.
AB  - The objective was to compare testis characteristics of Zebu bulls treated with
      the GnRH agonist, deslorelin, at different times and for different durations
      during their development. An additional objective was to determine the usefulness
      of a stain for the transcription factor GATA-binding protein 4 (GATA-4) as a
      specific marker for Sertoli cell nuclei in cattle. Bulls (54) were allocated to
      nine groups (n = 6) and received s.c. deslorelin implants as follows: G1 = from
      birth to 3 mo of age; G2 = from 3 to 6 mo; G3 = from 6 to 9 mo; G4 = from 9 to 12
      mo; G5 = from birth to 15 mo; G6 = from 3 to 15 mo; G7 = from 6 to 15 mo; G8 =
      from 12 to 15 mo; and G9 (control) = no implant. Bulls were castrated at 19 mo of
      age. Paraffin sections (10 microm) were subjected to quantitative morphometry and
      GATA-4 immunohistochemistry. At castration, all bulls in the control group (6/6)
      had attained puberty (scrotal circumference > or = 28 cm), whereas a smaller
      proportion (P < 0.05) had reached puberty in G2 (2/5) and G6 (1/6). Bulls in G2
      and G6 also had a lesser (P < 0.05) testis weight compared with the control
      group. Total volume of seminiferous epithelium and total daily sperm production
      in G2 and G6 were only half that observed in the control group. Spermatids were
      observed in less than 50% of seminiferous tubules in G2, G6, and G7 compared with
      82% in the control group (P < 0.05). Staining for GATA-4 was specific for and
      abundant in the Sertoli cell nucleus in both pre- and postpubertal bulls, and no
      other cell nucleus inside the seminiferous tubule was positive for GATA-4. Total
      number of Sertoli cells was not affected by treatment (P = 0.45), but nuclear
      volume was smaller in G2 and G6 (P < 0.05) compared with the control group. In
      conclusion, treatment of Zebu bulls with deslorelin had no apparent beneficial
      effect on testis development and delayed puberty when treatment was initiated at
      3 mo of age. Staining for GATA-4 was a useful method for identifying and
      quantifying Sertoli cell nuclei in both pre- and postpubertal bulls.

PMID- 16100067
TI  - Effects of replacing pharmacological levels of dietary zinc oxide with lower
      dietary levels of various organic zinc sources for weanling pigs.
AB  - Two 28-d randomized complete block design experiments were conducted to evaluate
      the effects of concentrations and sources of Zn on growth performance of nursery
      pigs. Seven stations participated in Exp. 1, which evaluated the efficacy of
      replacing 2,500 ppm of Zn from ZnO with 125, 250, or 500 ppm of Zn from Zn
      methionine. A control diet with 125 ppm of supplemental Zn was included at all
      stations. A total of 615 pigs were used in 26 replicates. Average weaning age was
      20.6 d and the average initial BW was 6.3 kg. There were no differences in any
      growth response among the three supplemental Zn methionine levels fed in Exp. 1.
      Zinc supplementation from Zn methionine improved ADG compared with the control
      during all phases (P < 0.05), due primarily to an increase in ADFI. Pigs fed
      2,500 ppm of Zn from ZnO gained faster (P < 0.01) than those fed the control diet
      during all phases, and faster (P < 0.05) than those fed supplemental Zn from Zn
      methionine for the 28-d experiment. Differences in gain were again due mainly to
      differences in feed intake. A second experiment compared five sources of
      supplemental organic Zn (500 ppm of Zn) with 500 and 2,000 ppm supplemental Zn
      from ZnO and a control (140 ppm total Zn). Six stations used a total of 624 pigs,
      with an average weaning age of 20.4 d and averaging 6.2 kg BW in 15 replicates.
      Pigs fed 2,000 ppm of Zn from ZnO gained faster (P < 0.05) than pigs fed the
      control or any of the 500 ppm of Zn treatments (ZnO or organic Zn). Pigs fed the
      2,000 ppm of Zn from ZnO also consumed more feed than those receiving 500 ppm of
      Zn from ZnO or from any of the organic Zn sources (P < 0.05). Organic sources of
      Zn did not improve gain, feed intake, or feed efficiency beyond that achieved
      with the control diet. Supplemental Zn at a concentration of 500 ppm, whether in
      the form of the oxide or in an organic form, was not as efficacious for improved
      ADG as 2,000 to 2,500 ppm of Zn from ZnO.

PMID- 16100068
TI  - Effect of phytase supplementation to a low- and a high-phytate diet for growing
      pigs on the digestibilities of crude protein, amino acids, and energy.
AB  - Supplementation of microbial phytase usually improves the digestibility and
      utilization of phosphorus in feedstuffs of plant origin. The effect of phytase
      supplementation on the digestibilities of AA also has been examined, but the
      results have been inconsistent. This study was carried out to determine the
      effect of phytase (Natuphos) supplementation, at a rate of 2,000 phytase
      units/kg, to two basal diets on the apparent ileal digestibilities (AID) of GE,
      CP, and AA, and on the apparent total-tract digestibilities (ATTD) of CP and GE.
      The basal diets contained 18% CP and were formulated (as-fed basis) to contain
      either a low (0.22%) or high content (0.48%) of phytate P. The high-phytate diet
      contained 20% rice bran, which is a rich source of phytate and has low intrinsic
      phytase activity. Eight barrows (average initial BW = 40.6 kg), fitted with a
      simple T-cannula at the distal ileum, were fed the four diets according to a
      replicated 4 x 4 Latin square design. The pigs were fed twice daily at 0800 and
      2000, equal amounts each meal, at a rate of 2.4 times the daily maintenance
      requirement for ME. Each experimental period comprised 14 d. Ileal digesta were
      collected from 0800 to 2000 on d 12, 13, and 14. Feces were collected from 0800
      on d 8 until 0800 on d 12. Chromic oxide was used as the digestibility marker.
      The AID of GE, CP, and AA and the ATTD of CP and GE were less in the high- than
      in the low-phytate diet (P < 0.01). With the exception of glutamic acid, phytase
      supplementation did not affect (P > 0.10) the AID of CP and AA. There was no
      effect (P > 0.05) of phytase on the ATTD of CP and GE. These results show that if
      a response occurs to phytase supplementation, it is independent of the dietary
      phytate content.

PMID- 16100069
TI  - Effects of iron supplementation on binding activity of iron regulatory proteins
      and the subsequent effect on growth performance and indices of hematological and
      mineral status of young pigs.
AB  - Two experiments were conducted to evaluate the effects of supplemental Fe on the
      binding activity of iron regulatory proteins (IRP) and the subsequent effect on
      growth performance and indices of hematological and mineral status of young pigs.
      In Exp. 1, male pigs (n = 10; 1.8 kg; age = 14 +/- 1 h) were allotted by BW to
      two treatments (five pigs per treatment). Treatments administered by i.m.
      injection were as follows: 1) 1 mL of sterile saline solution (Sal); and 2) 1 mL
      of 200 mg Fe as Fe-dextran (Fe). Pigs were bled (d 0 and 13) to determine
      hemoglobin (Hb), hematocrit (Hct), transferrin (Tf), and plasma Fe (PFe), and
      then killed (d 13) to determine spontaneous and 2-mercaptoethanol (2-ME)
      inducible IRP RNA binding activity in liver and liver and whole-body mineral
      concentrations. Contemporary pigs (n = 5; 2.2 kg; age = 14 +/- 2 h) were killed
      at d 0 to establish baseline (BL1) measurements. In Exp. 2, pigs (six pigs per
      treatment; 6.5 kg; age = 19 +/- 3 d) were fed a basal diet (Phase 1 = d 0 to 7;
      Phase 2 = d 7 to 21; Phase 3 = d 21 to 35) supplemented with 0 or 150 mg/kg of Fe
      as ferrous sulfate and killed at d 35 (18.3 kg; age = 54 +/- 3 d). In addition,
      pigs (n = 5; 5.9 kg; age = 19 +/- 3 d) were killed at the start of Exp. 2 to
      establish baseline (BL2) measurements, and liver samples were collected and
      analyzed for IRP RNA binding activity. In Exp. 1, no difference (P = 0.482) was
      observed in ADG. On d 13, Fe-treated pigs had greater (P = 0.001) Hb, Hct, and
      PFe and less (P = 0.002) Tf than Sal-treated pigs. Whole-body Fe concentration
      was greater (P = 0.002) in Fe- vs. Sal-treated pigs. Treated pigs (Fe or Sal) had
      greater (P = 0.006) whole-body Cu and less (P = 0.002) whole-body Ca, Mg, Mn, P,
      and Zn concentrations than BL1. Liver Fe concentration was greater (P = 0.001) in
      Fe- vs. Sal-treated pigs, but liver Fe concentration of Sal-treated pigs was less
      (P = 0.001) than that of BL1 pigs. Sal-treated pigs had greater (P = 0.004)
      spontaneous IRP binding activity than Fe-treated pigs. In Exp. 2, spontaneous and
      2-ME inducible IRP binding activities were greater (P = 0.013 and 0.005,
      respectively) in pigs fed diets containing 0 vs. 150 mg of added Fe/kg of diet.
      Moreover, pigs fed either treatment for 35 d had greater (P = 0.001) 2-ME
      inducible IRP binding activity than BL2 pigs. Results indicate that IRP binding
      activity is influenced by Fe supplementation. Subsequently, other indicators of
      Fe status are affected via the role of IRP in posttranscriptional expression of
      Fe storage and transport proteins.

PMID- 16100070
TI  - Effect of restricted forage intake on ruminal disappearance of bromegrass hay and
      a blood meal, feather meal, and fish meal supplement.
AB  - Two experiments were conducted to determine in situ disappearance of bromegrass
      hay and a ruminally undegraded protein (RUP) supplement in beef cattle fed
      restricted amounts of forage. Six Angus crossbred cattle (BW = 589 +/- 44.4 kg;
      three steers and three heifers) fitted with ruminal cannulas were fed chopped
      (2.54 cm) bromegrass hay (8.9% CP) at one of three percentages of maintenance
      intake (30, 55, or 80%; one steer and one heifer per treatment). In both
      experiments, the cattle were allowed 7 d for diet adaptation followed by 3 d of
      sample collection. In Exp 1, in situ bags (50 microm pore size) containing 4.1 g
      of brome-grass hay (OM basis) were inserted into the rumen and subsequently
      removed at 3, 6, 9, 12, 15, 18, 24, 36, and 48 h after insertion. Nonlinear
      regression models were used to determine the rapidly solubilized protein Fraction
      A, the potentially ruminal degradable protein Fraction B, the ruminally
      undegraded protein Fraction C, and protein degradation rate. Intake level did not
      affect (P = 0.15 to 0.95) forage protein remaining after in situ incubation or
      Fractions A, B, and C; however, effective ruminal degradation of hay protein
      tended to increase quadratically (P = 0.12) as forage intake increased. In Exp 2,
      4.2 g (OM basis) of an RUP supplement (6.8% porcine blood meal, 24.5% hydrolyzed
      feather meal, and 68.7% menhaden fish meal) formulated to provide equal amounts
      of metabolizable protein across all levels of hay consumption was evaluated in a
      similar manner as in Exp 1. The undegraded protein fraction of the supplement did
      not differ (P = 0.16 to 0.74) across treatments at 3, 6, 9, and 18 h; however,
      increasing forage intake resulted in a linear increase (P < or = 0.06) in
      undegraded protein remaining at 12, 15, 24, 36, and 48 h. Dietary treatment had
      no affect (P = 0.30) on protein Fractions A, B, or C; however, protein
      degradation rate of the supplement decreased linearly (P = 0.03) as forage intake
      increased. Therefore, effective ruminal degradation of the supplement decreased
      linearly (P = 0.01) from 50.8 to 40.9% as forage intake increased from 30 to 80%
      of maintenance. Corresponding estimates of supplement RUP were 49.2, 56.5, and
      59.1% for the 30, 55, and 80% of maintenance intake treatments, respectively.
      Restricting dietary intake can decrease the quantity of dietary protein that
      escapes ruminal degradation. Tabular estimates of RUP may not be appropriate for
      formulating diets to balance metabolizable protein in beef cattle consuming
      limited quantities of forage.

PMID- 16100071
TI  - Supplementing a ruminally undegradable protein supplement to maintain essential
      amino acid supply to the small intestine when forage intake is restricted in beef
      cattle.
AB  - Twelve Angus crossbred cattle (eight heifers and four steers; average initial BW
      = 594 +/- 44.4 kg) fitted with ruminal and duodenal cannulas and fed restricted
      amounts of forage plus a ruminally undegradable protein (RUP) supplement were
      used in a triplicated 4 x 4 Latin square design experiment to determine
      intestinal supply of essential AA. Cattle were fed four different levels of
      chopped (2.54 cm) bromegrass hay (11.4% CP, 57% NDF; OM basis): 30, 55, 80, or
      105% of the forage intake required for maintenance. Cattle fed below maintenance
      were given specified quantities of a RUP supplement (6.8% porcine blood meal,
      24.5% hydrolyzed feather meal, and 68.7% menhaden fish meal; DM basis) designed
      to provide duodenal essential AA flow equal to that of cattle fed forage at 105%
      of maintenance. Experimental periods lasted 21 d (17 d of adaptation and 4 d of
      sampling). Total OM intake and duodenal OM flow increased linearly (P < 0.001) as
      cattle consumed more forage; however, OM truly digested in the rumen (% of
      intake) did not change (P = 0.43) as intake increased. True ruminal N degradation
      (% of intake) tended (P = 0.07) to increase linearly, and true ruminal N
      degradation (g/d) decreased quadratically (P = 0.02) as intake increased from 30
      to 105%. Duodenal N flow was equal (P = 0.33) across intake levels, even though
      microbial N flow increased linearly (P < 0.001) as forage OM intake increased.
      Total and individual essential AA intake decreased (cubic; P < 0.001) as forage
      intake increased because the supply of nonammonia, nonmicrobial N flow from RUP
      was decreased (linear; P < 0.001) by design. Total duodenal flow of essential AA
      did not differ (P = 0.39) across these levels of forage intake. Although the
      profile of essential AA reaching the duodenum differed (P < or = 0.02) for all 10
      essential AA, the range of each essential AA as a proportion of total essential
      AA was low (11.1 to 11.2% of total essential AA for phenylalanine to 12.3 to
      14.3% of total essential AA for lysine). Duodenal essential AA flow did not
      differ (P = 0.10 to 0.65) with forage intake level for eight of the 10 essential
      AA. Duodenal flow of arginine decreased linearly (P = 0.01), whereas duodenal
      flow of tryptophan increased linearly (P = 0.002) as forage intake increased from
      30 to 105% of maintenance. Balancing intestinal essential AA supply in beef
      cattle can be accomplished by varying intake of a RUP supplement.

PMID- 16100072
TI  - Effects of dietary n-6 or n-3 polyunsaturated fatty acids protected or not
      against ruminal hydrogenation on plasma lipids and their susceptibility to
      peroxidation in fattening steers.
AB  - Two experiments were conducted using crossbred Salers x Charolais fattening
      steers fed diets enriched with no supplemental oilseeds or oils rich in either n
      6 PUFA (from sunflower seeds) or n-3 PUFA (from linseeds) provided either as
      seeds incorporated in the diet (i.e., not protected from ruminal bacterial
      hydrogenation) or by chronic infusion into the duodenum (protected form). In the
      Sunflower experiment, animals (initial age = 454 +/- 20 d; initial BW = 528 +/-
      36 kg) received a control diet for 70 d (CS, n = six) consisting of hay and
      concentrate, or the same basal diet supplemented with sunflower oil (4% of
      dietary DM), either fed as seeds (SS, n = six) or infused into the duodenum (ISO,
      n = six). The same experimental design was applied to animals (initial age = 412
      +/- 33 d; initial BW = 536 +/- 33 kg) used in the Linseed experiment (CL, LS, and
      ILO; n = 8 per group). For all animals, blood was sampled every 15 d during 70 d.
      In both trials, a significant diet x time interaction (P < 0.001) was detected
      for plasma concentrations of apolipoprotein A-I, phospholipids, and free and
      esterified cholesterol, with values increasing with time during administration of
      the PUFA-rich diets being more evident with ISO and ILO diets. Plasma fatty acids
      were altered with oil infusions, with increased concentrations of n-6 (1.6-fold;
      P < 0.05) and n-3 PUFA (4.5-fold; P < 0.05) and of their respective indicies of
      peroxidizability (1.2- and 1.5-fold with Diets ISO and ILO, respectively; P <
      0.05). In vitro copper-induced peroxidation of lipids revealed a decreased length
      of the lag phase in the process of conjugated diene generation by 48% (P < 0.005)
      with the ILO diet, indicating less resistance against peroxidation than in
      control steers. Compared with CS, the ISO treatment increased plasma alpha
      tocopherol (x2.5; P < 0.05) leading to similar resistance against peroxidation.
      After depletion of this vitamin, the rates of peroxidation and production of
      conjugated dienes were greater (twofold; P < 0.05) with the ISO and ILO diets
      than with the others. In conclusion, infusion of sunflower or linseed oil into
      the duodenum altered the composition and distribution of plasma lipids and
      increased the plasma concentration of PUFA. The sensitivity of plasma PUFA to
      peroxidation depends on the plasma level of antioxidants, especially vitamin E, a
      nutrient important both for the health of animals and for the stability of the
      blood lipids until their tissue deposit.

PMID- 16100073
TI  - Supplemental safflower oil affects the fatty acid profile, including conjugated
      linoleic acid, of lamb.
AB  - The objective of this study was to determine whether increasing levels of dietary
      safflower oil would alter unsaturated fat (especially CLA) and tocopherol content
      of lamb, animal performance, carcass characteristics, or color stability of lamb
      muscle tissue. Targhee x Rambouillet wethers (n = 60) were assigned to one of
      three diets (four pens per treatment with five lambs per pen) in a completely
      random design. Diets were formulated with supplemental safflower oil at 0
      (control), 3, or 6% (as-fed basis) of the diet. Diets containing approximately
      80% concentrate and 20% roughage were formulated, on a DM basis, to be isocaloric
      and isonitrogenous and to meet or exceed NRC requirements for Ca, P, and other
      nutrients. A subsample of 12 wethers per treatment was selected based on average
      BW (54 kg) and slaughtered. Carcass data (LM area, fat thickness, and internal
      fat content) and wholesale cut weight (leg, loin, rack, shoulder, breast, and
      foreshank), along with fatty acid, tocopherol, and color analysis, were
      determined on each carcass. The LM and infraspinatus were sampled for fatty acid
      profile. Increasing safflower oil supplementation from 0 to 3 or 6% increased the
      proportion of linoleic acid in the diet from 49.93 to 55.32 to 62.38%,
      respectively, whereas the percentage of oleic acid decreased from 27.94 to 23.80
      to 20.73%, respectively. The percentage of oil in the diet did not (P > or =
      0.11) alter the growth and carcass characteristics of lambs, nor did it alter the
      tocopherol content or color stability of meat. Increasing levels of safflower oil
      in lamb diets decreased (P < 0.01) the weight percentage of oleic acid in the
      infraspinatus and LM, and increased linoleic acid (P < 0.01). Oil supplementation
      increased (P < 0.01) the weight percentage of various isomers of CLA in muscle,
      with the greatest change in the cis-9,trans-11 isomer. Supplementation of sheep
      diets with safflower oil, up to 6% of the diet, resulted in increasing levels of
      unsaturated fatty acids and CLA in the lean tissue, without adversely affecting
      growth performance, carcass characteristics, or color stability of lamb.

PMID- 16100074
TI  - An assessment of extraction and assay techniques for quantification of calpain
      and calpastatin from small tissue samples.
AB  - Our objective was to evaluate whether small (biopsy-sized) samples could be used
      to measure calpain and calpastatin activities in skeletal muscle. The accuracy of
      different separation and assay methods for the quantification of calpains and
      calpastatin from small (1.0 and 0.2 g) skeletal muscle samples was tested. In
      Exp. 1, the LM was removed from six lambs, and a 50-g subsample was processed
      using the reference method (DEAE-Sephacel chromatography and casein assay).
      Subsamples (1.0 and 0.2 g) also were processed using the two-step separation (1
      mL DEAE-Sephacel and bulk elution using 200 and 400 mM NaCl) and heated
      calpastatin methods; in both cases, fractions were assayed with Bodipy-labeled
      and [14C]-labeled casein microassays. Finally, casein zymography was used to
      separate and quantify the calpain proteases from 1.0-and 0.2-g samples. The
      values obtained after processing the 50-g sample using the reference method were
      judged most accurate, and the alternative approaches were compared with these.
      For each extraction and assay approach, we considered: 1) the effect of the
      sample size on the mean activity; 2) increased or decreased variation of data;
      and 3) the correlation relative to the reference method. Where possible, we
      compared the ratio of calpain to calpastatin activities determined using the
      alternative approaches with the ratios found using the reference method. These
      methodologies were further investigated in Exp. 2, where single homogenates from
      different tissues (heart, spleen, lung, and muscle) were assayed using the
      alternative approaches. Experiment 1 established that most of the approaches
      suffered from poor correlations and/or unacceptable variation. By using a large,
      homogenous sample in Exp. 2, however, we determined that this error was not due
      to the methodologies themselves. Therefore, the unacceptable variation found in
      Exp. 1 resulted from the small sample size, and we recommend that large tissue
      samples (e.g., 50 g) should be used for calpain and calpastatin activity
      measurements in skeletal muscle instead of small tissue biopsies (e.g., 0.2 and
      1.0 g).

PMID- 16100075
TI  - Effect of calcium chloride, zinc chloride, and water infusion on metmyoglobin
      reducing activity and fresh lamb color.
AB  - Calcium chloride (CaCl2), zinc chloride (ZnCl2), or water infusions were used to
      investigate the biochemical factors that affect fresh lamb color, and to examine
      the role of metmyoglobin-reducing activity in regulating this important quality
      attribute. Immediately after exsanguination, lamb carcasses (n = 6 per treatment)
      were infused (10% of BW) with 0.3 M CaCl2, 0.05 M ZnCl2, or water via a catheter
      inserted into the left carotid artery. The right LM was excised at 24-h
      postmortem and divided into two halves. The caudal portion was cut into 2.5-cm
      thick chops and displayed for 6 d under 1,076 lx of white fluorescent lighting at
      2 degrees C, whereas the cranial half was vacuum-packaged and stored at 2 degrees
      C for 3 wk before retail display. Objective color measurements and samples for
      biochemical analysis were taken at 0, 1, 3, and 6 d of display. In infused
      carcasses, pH decline was more rapid (P < 0.05) than in untreated controls, and
      it was greatest for CaCl2-infused carcasses. Calcium chloride-infused carcasses
      had lower (P < 0.01) NAD and higher (P < 0.001) NADPH concentrations than water-
      and ZnCl2-infused or untreated control carcasses. The negative effects of calcium
      infusion on fresh lamb color, higher (P < 0.01) metmyoglobin accumulation rate,
      and lower (P < 0.01) L*, a*, and b* color measurements could be explained by the
      lower amounts of unbound water (P < 0.01), shorter sarcomere length (P < 0.01),
      lower NAD concentrations (P < 0.01), and higher lipid peroxidation (P < 0.01).
      Zinc and water-infusions produced less (P < 0.01) lipid oxidation and improved
      the color and color stability of fresh lamb (P < 0.001). Rate of lipid oxidation
      in LM chops was greater (P < 0.01) after 3 wk of vacuum-packaged storage than 24
      h postmortem. Metmyoglobin-reducing activities (sarcoplasmic and myofibrillar)
      were decreased in response to infusion treatments (P < 0.001), and ZnCl2 infusion
      resulted in the lowest metmyoglobin-reducing activities (P < 0.001). A
      significant association between the myofibrillar metmyoglobin-reducing activity
      and lipid peroxidation was observed, but metmyoglobin-reducing activities were
      not associated with any improvement in lamb color. Strategies to increase the
      antioxidant levels in lamb are very important to improve lamb quality, especially
      during vacuum-packaging storage.

PMID- 16100076
TI  - The effects of weaning beef calves in two stages on their behavior and growth
      rate.
AB  - Four trials were conducted to explore possible advantages of weaning beef calves
      in two stages compared with the traditional method of weaning by abrupt
      separation. In the two-stage treatment, calves were prevented from nursing their
      dam for a period (Stage 1) before their separation (Stage 2). Control calves
      nursed from their dams until they were separated. Calf weights and behavior were
      recorded before and after the separation of cows and calves. Following
      separation, calves weaned in two stages vocalized 96.6% less (P = 0.001) and
      spent 78.9% less time walking (P = 0.001), 23.0% more time eating (P = 0.001),
      and 24.1% more time resting (P = 0.001) than control calves. Compared with
      controls, two-stage calves had lower (P < 0.001) ADG when nursing was deprived
      (Stage 1), but greater (P < 0.001) ADG during the 7 d following separation. In
      Trial 3, calves weaned by the two-stage method had greater (P = 0.05) growth
      rates than control calves for 7 wk after separation, but no treatment effects on
      ADG were detected (P > 0.38) in Trials 1 and 2. Over the entire study period
      (before and after separation), ADG did not differ (P > 0.10) for both treatments.
      In Trial 4, calves weaned in two stages walked 1.3 km/d more (P < 0.05) during
      the 4-d period when nursing was prevented (Stage 1) and 5.8 km/d less (P < 0.05)
      during the 4-d period after separation than controls. Differences between
      treatments were the greatest in the 2 d after separation. On the first day after
      separation, two-stage calves walked 5.2 +/- 0.5 km/ d, whereas control calves
      walked 16.7 +/- 3.1 km/d. Calves weaned in two stages were less distressed than
      calves weaned by the traditional method of abrupt separation based on behavioral
      data, but overall calf ADG did not differ for either method in this study.
      Nutritional management of two-stage weaned calves during the nursing-deprived
      period should be evaluated in future research because poor pasture conditions may
      have decreased gains by calves weaned by the two-stage method in this study.

PMID- 16100077
TI  - Use of ear tags and injectable transponders for the identification and
      traceability of pigs from birth to the end of the slaughter line.
AB  - A total of 557 newborn piglets were used to compare eight identification devices,
      including one plastic ear tag as a control (C, n = 348) and two types of
      electronic ear tags (E1, n = 106; and E2, n = 103), and five types of injectable
      transponders (n = 557): small 12-mm (D12, n = 116; and S12, n = 110), medium 23
      mm (T23, n = 108), and large (32-mm, T32, n = 115; and 34-mm, S34, n = 108).
      Injections were made s.c. in the auricle base (n = 248) and intraperitoneally (n
      = 309) using a new technique. All piglets were identified with two devices, but
      using electronic ear tags in conjunction with injection in the auricle was
      avoided on the same pig. Readability of devices was checked during fattening
      (until 110 kg BW) and slaughtering. On-farm losses were lower for control than
      for electronic ear tags (C = 1.1%; E1 = 8.8%; and E2 = 44.9%; P < 0.01); the
      latter also suffered electronic failures (E1 = 5.5%; and E2 = 55.1%; P < 0.001).
      On-farm losses of transponders injected in the auricle base were greater in large
      (S34 = 72.5%; and T32 = 46.3%; P < 0.05) than in small transponders (S12 = 19.4%;
      and D12 = 17.1%), but T23 (29.8%) only differed from S34. Transponder size did
      not affect on-farm losses for intraperitoneal injections in which only one loss
      was recorded (0.4%). All ear tags had similar losses during transportation to the
      slaughterhouse (1.2%), but no losses were observed in injectables. Slaughtering
      losses did not differ between ear tags (C = 11.2%; and E1 = 6.4%), but apart from
      losses, 12.8% of E1 failed electronically. Injection site affected losses and
      breakages during slaughtering (auricle base = 6.4%; and intraperitoneal = 0%),
      but recovery time did not significantly differ (auricle base = 28.6 s; and
      intraperitoneal = 18.9 s). Transponders in the auricle base were recovered by
      sight (30.2%), palpation (27.4%), or by cutting (42.5%). Intraperitoneal
      transponders were mainly recovered loose in the abdominal cavity (81.4%), whereas
      18.6% fell on the floor. As a result, traceability varied significantly (P <
      0.05) between control (86.7%) and electronic ear tags (0 to 68.1%) and injectable
      transponders, with the auricle base (17.8 to 75.0%) having lower values than
      intraperitoneal (98 to 100%). Intraperitoneal injection was a very effective tool
      for piglet identification and traceability, ensuring the transfer of information
      from farm to slaughterhouse. To warrant the use of this technique in practice,
      transponder recovery requires further investigation.

PMID- 16100078
TI  - Behavior, preference for, and use of alfalfa, tall fescue, white clover, and
      buffalograss by pregnant gilts in an outdoor production system.
AB  - Sustainable outdoor pig production requires vegetation that can maintain ground
      cover, assimilate manure nutrients, and prevent soil erosion. Two experiments
      were conducted to evaluate the suitability of four forages: alfalfa (Medicago
      sativa), tall fescue (Festuca arundinacea), white clover (Trifolium repens), and
      buffalograss (Buchloe dactyloides) for grazing or ground cover in pastures for
      pigs. Each forage plot covered 7.5 m2, with nine replicates in a randomized block
      design. In Exp. 1, eight pregnant gilts had free access to all forages during a 2
      d adjustment period. Immediately thereafter, pairs of gilts were assigned
      randomly to one of each of four blocks of the four forages during a 2-d
      measurement period. The percentage of ground cover for each forage was visually
      estimated at 0, 24, and 48 h of study. Behavioral data, including walking,
      eating, grazing, rooting, drinking, standing, lying, and time spent in hut were
      video-monitored continuously for 48 h. Initial percentage of ground cover was
      100% for all species. By 48 h, percentage of ground cover decreased (P < 0.001)
      for white clover (11.3 +/- 0.88%) and alfalfa (36.3 +/- 0.88%), but not for tall
      fescue (98.0 +/- 0.88%) or buffalograss (98.0 +/- 0.88%). Gilts spent more (P <
      0.01) time grazing white clover (16.3 +/- 1.97 min/d) and alfalfa (11.2 +/- 1.97)
      than tall fescue (0.8 +/- 1.97) or buffalograss (0.3 +/- 1.97), and rooted more
      (P < 0.04) white clover than other forages. In Exp. 2, six gilts from the initial
      group were put on six blocks of the four forages. Each gilt was assigned randomly
      to three replicates of each forage, including alfalfa, tall fescue, or
      buffalograss (white clover was excluded because of damage by gilts during Exp.
      1), and gilts grazed single forages for 2 d. After this grazing period, the
      percentage of ground cover was less (P < 0.01) for alfalfa than for buffalograss
      or tall fescue (37.5 +/- 0.38, 96.7 +/- 0.39, 96.3 +/- 0.39%, respectively). With
      access to a single forage, pregnant gilts spent more (P < 0.01) time grazing
      alfalfa (15.8 +/- 2.36 min/d) than buffalograss (1.5 +/- 2.36) or tall fescue
      (0.7 +/- 2.37). These gilts clearly preferred grazing white clover and alfalfa,
      and rooting and eating white clover compared with buffalograss or tall fescue.
      Rates of ground cover loss were less (P < 0.01) for tall fescue and buffalograss
      than for the more preferred forages. Less preferred forages could have potential
      as pasture for swine when the primary objective is ground cover maintenance
      rather than nutrient supply.

PMID- 16100079
TI  - Effects of stocking and nitrogen fertilization rates on steers grazing
      dallisgrass-dominated pasture.
AB  - To compare the performance of steer calves managed under different stocking rates
      (SR; 3.7, 6.2, 8.6, and 11.1 steers/ha for 140 d; chi(I1)) and N fertilization
      rates (112, 224, and 336 kg of N/ha; chi(I2)) in May 1996, 1997, and 1998, 72
      steer calves (BW = 231 +/- 2.5 kg) were assigned randomly to one of 12 0.81-ha
      dallisgrass (51%)/common bermudagrass (32%) pastures. One-third of the fertilizer
      was applied in the form of ammonium nitrate in May, June, and August to achieve
      the prescribed totals. Treatments were separated using a polynomial regression
      equation: gammai = beta0 + beta1chi(I1) + beta2chi(I2) + beta(11)chi2(I1) +
      beta(12)chi2(I2) + beta(12)chi(i1)chi(i2) + epsilonI, with years as replicates.
      Within the range of the data, ADG and BW gain per steer were greatest at a
      stocking rate of 3.7 steers/ha and 336 kg/ha of N. Body weight gain per hectare
      peaked at 701 kg when cattle were stocked at 8.9 steers/ha and the pasture was
      fertilized with 336 kg/ha of N. The least cost of production was at a stocking
      rate of 3.7 steers/ha, with 112 kg/ha of fertilizer N applied, and the greatest
      cost of production was at a stocking rate of 11.1 steers/ha with 336 kg/ha of
      fertilizer N applied. Fertilization at 336 kg/ha of N produced the most
      profitable stocking rate at 7.3 steers/ha and returned 355.64 dollars. The
      optimal stocking rate for net return was 79, 81, and 82% of that for maximum BW
      gain per hectare for 112, 224, and 336 kg/ha of N, respectively. Under the
      assumptions made in the financial analysis, these data show that the economically
      optimal carrying capacity of similar pastures can be increased with N fertilizer
      up to at least 336 kg/ha annually.

PMID- 16100080
TI  - An essential role for non-bone marrow-derived cells in control of Pseudomonas
      aeruginosa pneumonia.
AB  - MyD88 is an adapter protein required for the induction of proinflammatory
      cytokines by most Toll-like receptors (TLR), and Pseudomonas aeruginosa expresses
      ligands for multiple TLRs. MyD88(-/-) (KO) mice are highly susceptible to
      aerosolized P. aeruginosa, failing to elicit an early inflammatory response and
      permitting a 3-log increase in bacterial CFU in the lungs by 24 h after
      infection. We hypothesized that alveolar macrophages are the first cells to
      recognize and kill aerosolized P. aeruginosa in an MyD88-dependent fashion due to
      their location within the airways. To determine which cells in the lungs mediate
      MyD88-dependent defenses against P. aeruginosa, we generated radiation bone
      marrow (BM) chimeras between MyD88KO and wild-type (WT) mice. MyD88KO mice
      transplanted with MyD88KO BM (MyD88KO-->MyD88KO mice) displayed uncontrolled
      bacterial replication, whereas all other chimeras controlled the infection by 24
      h. However, at 4 h, both MyD88KO-->MyD88KO and WT-->MyD88KO mice permitted
      intrapulmonary bacterial replication, whereas MyD88KO-->WT and WT-->WT mice did
      not, indicating that the source of BM had little impact on the early control of
      infection. Similarly, the genotype of the recipient rather than that of the BM
      donor determined early neutrophil recruitment to the lungs. Whereas
      intrapulmonary TNF-alpha and IL-1beta production were associated with WT BM,
      levels of the CXC chemokines MIP-2 and KC as well as GM-CSF were associated with
      recipient genotype. We conclude that lung parenchymal and BM-derived cells
      collaborate in the MyD88-dependent response to P. aeruginosa infection in the
      lungs in mice.

PMID- 16100082
TI  - Facing the new threats of terrorism: radiologists' perspectives based on
      experience in Israel.
AB  - On September 11, 2001, the world changed. The vicious giant of terrorism that was
      dormant until that date had arisen. After the horrific mass-casualty terror
      attack on the United States, any and all forms of assault seem possible. Owing to
      the complexity of injuries encountered in terror attack victims, fast and
      accurate imaging plays an essential role in triage and identification of
      abnormalities associated with injuries. The radiologist becomes a crucial part of
      the first-line team of doctors treating these patients. Knowledge that the best
      available treatment is given to terror attack victims can enhance the strength
      and endurance of society against terror. On the basis of the authors' experience
      with terror events in Israel, the steps involved in imaging of terror attack
      patients include conventional radiography, focused abdominal sonography in
      trauma, computed tomography, and angiography, with the judicious use of
      supplemental imaging.

PMID- 16100081
TI  - Involvement of calpain-calpastatin in cigarette smoke-induced inhibition of lung
      endothelial nitric oxide synthase.
AB  - We reported that cigarette smoke extract (CSE) causes decreases in the activity
      and expression of endothelial nitric oxide synthase (eNOS) and calpain activity
      in pulmonary artery endothelial cells (PAECs). Calpains are a family of calcium
      dependent endopeptidases, and their specific endogenous inhibitor is calpastatin.
      In this study, we evaluated the role of calpain-calpastatin in CSE-induced
      decrease in eNOS gene expression. PAEC were incubated with 5-10% CSE for 2-24 h.
      eNOS gene transcription rate, eNOS messenger ribonucleic acid (mRNA) half-life,
      and the activity and protein contents of calpain and calpastatin were measured.
      Incubation of PAEC with CSE caused significant decreases in eNOS gene
      transcription and calpain activity and an increase in calpastatin protein
      content. eNOS mRNA half-life was not significantly altered by CSE. To investigate
      whether CSE-induced inhibition of eNOS gene expression is caused by decreased
      calpain activity due to an increase in calpastatin protein content, we cloned
      calpastatin gene from PAEC and constructed adenovirus vectors containing
      calpastatin. Overexpression of calpastatin mimics the inhibitory effects of CSE
      on calpain activity and on the activity, protein, and mRNA of eNOS. The cell
      permeable calpain inhibitor, calpastatin peptide, inhibits acetylcholine-induced
      endothelium-dependent relaxation of the pulmonary artery. Incubation of PAEC with
      an antisense oligodeoxyribonucleotide of calpastatin prevented CSE-induced
      increases in calpastatin protein and CSE-induced decreases in calpain activity,
      eNOS gene transcription, activity and protein content of eNOS, and NO release.
      These results indicate that CSE-induced inhibition of eNOS expression in PAEC is
      caused by calpain inhibition due to an increase in calpastatin protein content.

PMID- 16100083
TI  - Vascular mapping of the leg with multi-detector row CT angiography prior to free
      flap transplantation.
AB  - PURPOSE: To retrospectively evaluate multi-detector row computed tomographic (CT)
      angiography in determining donor- and recipient-site arterial suitability for
      successful vascularized free-flap transplantation. MATERIALS AND METHODS: The
      institutional review board granted approval; informed consent was waived, and the
      study was HIPAA compliant. Lower extremities of 20 (12 male, eight female; mean
      age, 51 years; range, 10-84 years) patients undergoing vascularized free-flap
      procedures were examined at multi-detector row CT angiography. In five patients,
      legs were assessed as potential fibular free-flap donors for mandibular,
      maxillary, or radial reconstruction. In 15 patients, legs were assessed as
      recipient sites for free flaps. Vascular maps obtained with volume rendering,
      maximum intensity projections, and curved planar reformations were generated, and
      assessment was made in the depiction of calf vessels and presence of stenosis,
      occlusion, and anatomic anomaly. Findings of CT angiography, physical
      examination, and surgery were compared, where applicable, and successful CT-based
      prediction of the surgical intervention was assessed. Immediate and long-term
      (>70 days) viability of the graft was assessed in all patients. RESULTS: CT
      angiography depicted the entirety of all four major calf arteries in 29 of 32
      legs scanned. In three legs, external-fixation hardware obscured some segments.
      There were no discrepancies between CT findings and those identified at the time
      of surgery. Arterial abnormalities, including stenosis, occlusion, and variant
      anatomy, were seen in 12 lower extremities in 10 patients. Only two were
      suspected on the basis of physical examination findings. In five of 20 patients,
      CT findings resulted in changes to the surgical plan. There was a 100% immediate
      viability of all grafts, which remained well vascularized between 70 days and 37
      months after the procedure. CONCLUSION: Multi-detector row CT angiography
      provides a noninvasive means of preoperatively assessing lower extremity arteries
      for abnormalities, which could jeopardize graft viability or pedal arterial
      supply after free-flap procedures.

PMID- 16100084
TI  - Lymphomatoid granulomatosis: abnormalities of the brain at MR imaging.
AB  - PURPOSE: To retrospectively evaluate the magnetic resonance (MR) imaging features
      of lymphomatoid granulomatosis in the brain. MATERIALS AND METHODS: The study,
      including retrospective analysis of data, was approved by the institutional
      review board of the National Cancer Institute and complied with Health Insurance
      Portability and Accountability Act. All patients gave written informed consent.
      Thirty-one patients with pathologically confirmed lymphomatoid granulomatosis
      were enrolled in a natural history and treatment study at the National Institutes
      of Health. Twenty-five patients (median age, 50 years; range, 18-62 years; 18
      men, seven women) were evaluated with MR imaging of the brain at study entry for
      the presence of brain lesions and enhancing characteristics. Patients with
      abnormal findings were reexamined at intervals ranging from 2 to 19 months, as
      medically indicated. Cytologic analysis and flow cytometry of cerebrospinal fluid
      (CSF) were performed. Statistical analysis was performed to compare neurologic
      and CSF findings in patients with brain MR imaging abnormalities and in patients
      without abnormalities. The sensitivity of brain MR imaging was compared with that
      of CSF studies. RESULTS: Thirteen (52%) of 25 patients evaluated with MR imaging
      had a variety of brain abnormalities. Multiple focal intraparenchymal lesions,
      which exhibited T2 prolongation and commonly punctate or linear enhancement, were
      the most frequent abnormalities, and they were encountered in seven patients. The
      second most common finding was involvement of leptomeninges and cranial nerves,
      which manifested as abnormal enhancement on MR images obtained after contrast
      agent administration. This abnormality was seen in six patients. Involvement of
      dura mater was noted in another. Four patients had brain masses. Two had abnormal
      engorgement and intense enhancement of the choroid plexus. Most lesions resolved
      after treatment, but seven resulted in lacunar infarctions. Abnormal B cells were
      detected in the CSF with either cytologic techniques or flow cytometry in five
      patients. CONCLUSION: Lymphomatoid granulomatosis has a high rate of central
      nervous system involvement and a variable spectrum of lesions at MR imaging.
      Findings in this study suggest that MR imaging is more sensitive than CSF
      cytologic analysis or flow cytometry for detection of central nervous system
      involvement from lymphomatoid granulomatosis.

PMID- 16100085
TI  - Imaging features of perivascular fatty infiltration of the liver: initial
      observations.
AB  - PURPOSE: To retrospectively identify and describe the imaging features that
      represent perivascular fatty infiltration of the liver. MATERIALS AND METHODS:
      The institutional review board approved the study and waived informed consent.
      The study complied with the Health Insurance Portability and Accountability Act.
      Ten patients (seven women, three men; mean age, 78 years; range, 31-78 years)
      with fatty infiltration surrounding hepatic veins and/or portal tracts were
      retrospectively identified by searching the abdominal imaging teaching file of an
      academic hospital. The patients' medical records were reviewed by one author.
      Computed tomographic (CT), magnetic resonance (MR), and ultrasonographic (US)
      imaging studies were reviewed by three radiologists in consensus. Fatty
      infiltration of the liver on CT images was defined as absolute attenuation less
      than 40 HU without mass effect and, if unenhanced images were available, as
      relative attenuation at least 10 HU less than that of the spleen; on gradient
      echo MR images, it was defined as signal loss on opposed-phase images compared
      with in-phase images; and on US images, it was defined as hyperechogenicity of
      liver relative to kidney, ultrasound beam attenuation, and poor visualization of
      intrahepatic structures. Perivascular fatty infiltration of the liver was defined
      as a clear predisposition to fat accumulation around hepatic veins and/or portal
      tracts. For multiphase CT images, the contrast-to-noise ratio was calculated for
      comparison of spared liver with fatty liver in each imaging phase. RESULTS: Fatty
      infiltration surrounded hepatic veins in three, portal tracts in five, and both
      hepatic veins and portal tracts in two patients. Six of the 10 patients had
      alcoholic cirrhosis, two reported regular alcohol consumption (one of whom had
      acquired immunodeficiency syndrome and hepatitis B), one was positive for human
      immunodeficiency virus, and one had no risk factors for fatty infiltration of the
      liver. In three of the 10 patients, fatty infiltration was misdiagnosed as
      vascular or neoplastic disease on initial CT images but was correctly diagnosed
      on MR images. CONCLUSION: Perivascular fatty infiltration of the liver has
      imaging features that allow its recognition.

PMID- 16100086
TI  - Breast lesion detection and classification: comparison of screen-film mammography
      and full-field digital mammography with soft-copy reading--observer performance
      study.
AB  - PURPOSE: To retrospectively compare screen-film and full-field digital
      mammography with soft-copy interpretation for reader performance in detection and
      classification of breast lesions in women in a screening program. MATERIALS AND
      METHODS: Regional ethics committee approved the study; signed patient consents
      were obtained. Two-view mammograms were obtained with digital and screen-film
      systems at previous screening studies. Six readers interpreted images.
      Interpretation included Breast Imaging Reporting and Data System (BI-RADS) and
      five-level probability-of-malignancy scores. A case was one breast, with two
      standard views acquired with both screen-film mammography and digital
      mammography. The standard for an examination with normal findings was
      classification of normal (category 1) assigned by two independent readers; for
      cases with benign findings, the standard was benign results at diagnostic work-up
      in patients who were recalled. Cases with normal or benign findings that
      manifested as neither interval cancer nor as cancer at subsequent screening were
      considered the standard. All cancers were confirmed histologically. Images were
      interpreted by readers in two sessions 5 weeks apart; the same case was not seen
      twice in any session. Receiver operating characteristic (ROC) analysis and, for a
      given true-positive fraction, 2 x 2 table analysis and the McNemar test were
      used. For binary outcome, classification of BI-RADS category 3 or higher was
      defined as positive for cancer. RESULTS: Cases with proved findings (n = 232)
      were displayed: 46 with cancers, 88 with benign findings, and 98 with normal
      findings. ROC analysis for all readers and all cases revealed a higher area under
      ROC curve (A(z)) for digital mammography (0.916) than for screen-film mammography
      (0.887) (P = .22). Five of six readers had a higher performance rating with
      digital mammography; one of five demonstrated a significant difference in favor
      of digital mammography with A(z) values; two showed a significant difference in
      favor of digital mammography with ROC analysis for a given false-positive
      fraction (P = .01 and .03, respectively). For cases with cancer, digital
      mammography resulted in correct classification of an average of three additional
      cancers per reader. For digital versus screen-film mammography, 2 x 2 table
      analysis for cancers revealed a higher true-positive rate; for benign masses, a
      higher true-negative rate. Neither of these differences nor any others from
      analysis of subgroups between the modalities were significant. CONCLUSION:
      Digital mammography allowed correct classification of more breast cancers than
      did screen-film mammography. A(z) value was higher for digital mammography; this
      difference was not significant.

PMID- 16100087
TI  - Colorectal liver metastases: CT, MR imaging, and PET for diagnosis--meta
      analysis.
AB  - PURPOSE: To perform a meta-analysis to obtain sensitivity estimates of computed
      tomography (CT), magnetic resonance (MR) imaging, and fluorine 18
      fluorodeoxyglucose (FDG) positron emission tomography (PET) for detection of
      colorectal liver metastases on per-patient and per-lesion bases. MATERIALS AND
      METHODS: MEDLINE, EMBASE, Web of Science, and CANCERLIT databases and Cochrane
      Database of Systematic Reviews were searched for relevant original articles
      published from January 1990 to December 2003. Criteria for inclusion of articles
      were as follows: Articles were reported in the English, German, or French
      language; CT, MR imaging, or FDG PET was performed to identify and characterize
      colorectal liver metastases; histopathologic analysis (surgery, biopsy, or
      autopsy), intraoperative observation (manual palpatation, intraoperative
      ultrasonography [US]), and/or follow-up US was the reference standard; and data
      were sufficient for calculation of true-positive or false-negative values. A
      random-effects linear regression model was used to obtain sensitivity estimates
      in assessment of liver metastases. RESULTS: Of 165 identified relevant articles,
      61 fulfilled all inclusion criteria. Sensitivity estimates on a per-patient basis
      for nonhelical CT, helical CT, 1.5-T MR imaging, and FDG PET were 60.2%, 64.7%,
      75.8%, and 94.6%, respectively; FDG PET was the most accurate modality. On a per
      lesion basis, sensitivity estimates for nonhelical CT, helical CT, 1.0-T MR
      imaging, 1.5-T MR imaging, and FDG PET were 52.3%, 63.8%, 66.1%, 64.4%, and
      75.9%, respectively; nonhelical CT had lowest sensitivity. Estimates of
      gadolinium-enhanced MR imaging and superparamagnetic iron oxide (SPIO)-enhanced
      MR imaging were significantly better, compared with nonenhanced MR imaging (P =
      .019 and P < .001, respectively) and with helical CT with 45 g of iodine or less
      (P = .02 and P < .001, respectively). For lesions of 1 cm or larger, SPIO
      enhanced MR imaging was the most accurate modality (P < .001). CONCLUSION: FDG
      PET had significantly higher sensitivity on a per-patient basis, compared with
      that of the other modalities, but not on a per-lesion basis. Sensitivity
      estimates for MR imaging with contrast agent were significantly superior to those
      for helical CT with 45 g of iodine or less.

PMID- 16100088
TI  - Intrinsic and extrinsic regulators of developmental timing: from miRNAs to
      nutritional cues.
AB  - A fundamental challenge in biology is to understand the reproducibility of
      developmental programs between individuals of the same metazoan species. This
      developmental precision reflects the meticulous integration of temporal control
      mechanisms with those that specify other aspects of pattern formation, such as
      spatial and sexual information. The cues that guide these developmental events
      are largely intrinsic to the organism but can also include extrinsic inputs, such
      as nutrition or temperature. This review discusses the well-characterized
      developmental timing mechanism that patterns the C. elegans epidermis. Components
      of this pathway are conserved, and their links to developmental time control in
      other species are considered, including the temporal patterning of the fly
      nervous system. Particular attention is given to the roles of miRNAs in
      developmental timing and to the emerging mechanisms that link developmental
      programs to nutritional cues.

PMID- 16100089
TI  - beta-Catenin-dependent Wnt signalling controls the epithelial organisation of
      somites through the activation of paraxis.
AB  - The regulation of cell adhesion in epithelia is a fundamental process governing
      morphogenesis in embryos and a key step in the progression of invasive cancers.
      Here, we have analysed the molecular pathways controlling the epithelial
      organisation of somites. Somites are mesodermal epithelial structures of
      vertebrate embryos that undergo several changes in cell adhesion during early
      embryonic life. We show that Wnt6 in the ectoderm overlaying the somites, but not
      Wnt1 in the neighbouring neural tube, is the most likely candidate molecule
      responsible for the maintenance of the epithelial structure of the dorsal
      compartment of the somite: the dermomyotome. We characterised the signalling
      pathway that mediates Wnt6 activity. Our experiments suggest that the Wnt
      receptor molecule Frizzled7 probably transduces the Wnt6 signal. Intracellularly,
      this leads to the activation of the beta-catenin/LEF1-dependent pathway. Finally,
      we demonstrate that the bHLH transcription factor paraxis, which was previously
      shown to be a major player in the epithelial organisation of somites, is a target
      of the beta-catenin signal. We conclude that beta-catenin activity, initiated by
      Wnt6 and mediated by paraxis, is required for the maintenance of the epithelial
      structure of somites.

PMID- 16100091
TI  - On squeezing blood out of turnips.

PMID- 16100093
TI  - Abnormalities of vasomotor regulation in the pathogenesis of the acute charcot
      foot of diabetes mellitus.
AB  - The acute Charcot foot complicates distal symmetrical neuropathy but is
      remarkably rare. This article reviews the multiple processes that may complicate
      both diabetes and neuropathy and might, in turn, explain the association of
      features that are typical of this disorder: osteolysis, vascular calcification in
      association with intact lower limb blood flow, and uncontrolled inflammation.
      Specifically, it is suggested that the disorder arises because of abnormal
      expression of the nuclear transcription factor, NFkappaB, in diabetic neuropathy
      and that this is further enhanced at the onset of the acute arthropathy as a
      result of the release of proinflammatory cytokines, such as tumor necrosis factor
      alpha and interleukin-1. These proinflammatory cytokines and RANKL may then enter
      a cycle of mutual augmentation, and this is a factor that underlies the
      continuing inflammation that characterizes the disorder. If this hypothesis is
      confirmed, it would suggest the option of new effective treatments for this
      sometimes devastating disorder.

PMID- 16100094
TI  - Apoptosis: a basic physiologic process in wound healing.
AB  - Apoptosis, or programmed cell death, is a complex network of biochemical pathways
      for controlling such events in a cell. Apoptosis is essential, as its failure can
      lead to disease. Because apoptosis concerns the regulation of sequential events,
      including the removal of inflammatory cells and the evolution of granulation
      tissue into scar tissue, it has an essential role in wound repair. This article
      examines the literature and proposes that apoptosis features in the development
      of diabetic foot wounds. Hyperglycemia deregulates the sequential apoptotic
      events by multiple mechanisms, leading to delayed wound healing. Deregulated
      apoptosis is emerging as a prominent cause of delayed wound healing, especially
      in diabetic wounds, along with the well-known triad of peripheral vascular
      disease, neuropathy, and infection.

PMID- 16100095
TI  - Infection in the neuroischemic foot.
AB  - Infection in the neuroischemic foot can lead to cellulitis, which often
      progresses to necrosis as a result of septic vasculitis. Therefore, it is
      important to diagnose infection early. However, the signs and symptoms of
      infection are diminished in the neuroischemic foot. Microbiological investigation
      is essential. Severe infection needs intravenous antibiotic therapy and urgent
      assessment of the need for surgical drainage and debridement. Infected
      neuroischemic feet need vascular assessment and intervention where appropriate.
      It is important to maintain strict metabolic control and optimize cardiovascular
      function. Recent modern approaches based on multi-disciplinary clinics have
      resulted in improved results in the management of infection in the ischemic
      diabetic foot.

PMID- 16100096
TI  - A review of the mechanisms implicated in the pathogenesis of the diabetic foot.
AB  - The developmental pathway toward diabetic foot ulceration is best described as
      multifactorial. A critical triad of neuropathy, minor foot trauma, and foot
      deformity has been identified in greater than 63% of foot ulcers. In addition to
      these risk factors, increased peak plantar pressures, autonomic and motor
      neuropathy, limited joint mobility, and impaired wound healing contribute to the
      formation of diabetic foot ulcers. It is essential to understand the pathogenesis
      of foot ulcers so that appropriate treatments may be developed.

PMID- 16100097
TI  - A review of the biomechanics of the diabetic foot.
AB  - In general, diabetic foot ulcers result from abnormal mechanical loading of the
      foot, such as repetitive moderate pressure applied to the plantar aspect of the
      foot while walking. Diabetic peripheral neuropathy causes changes in foot
      structure, affecting foot function and subsequently leading to increased plantar
      foot pressure, which is a predictive risk factor for the development of diabetic
      foot ulceration. Prevention of diabetic foot ulceration is possible by early
      identification of the insensitive foot, therefore a foot "at risk," and by
      protecting the foot from abnormal biomechanical loading. Abnormal foot pressures
      can be reduced using several different approaches, including callus debridement,
      prescription of special footwear, injection of liquid silicone, Achilles tendon
      lengthening, and so forth. Off-loading of the diabetic wound is a key factor in
      successful wound healing, as it is associated with reduced inflammatory and
      accelerated repair processes. Pressure relief can be achieved using various off
      loading modalities including accommodative dressing, walking splints, ankle-foot
      orthosis, total contact cast, and removable and irremovable cast walkers.

PMID- 16100098
TI  - Diabetic foot complications: diagnosis and management.
AB  - Foot complications in patients with diabetes mellitus are a challenge to the
      health care industry. A great deal of expenditure is due to the management of
      diabetic foot complications. This places a great burden on the health care
      industry. It also places a great burden on those diabetic patients with foot
      complications and their families. Therefore, their effective management in an
      efficient manner is crucial to our patients. To deal with these problems, a
      dedicated, knowledgeable, and experienced multidisciplinary team is key.
      Intervention at the earliest possible time yields the best outcome. Prevention is
      the focus for those with no ulcerations. For those with ulcerations, prompt
      recognition and treatment is key. The importance of classifying ulcerations
      according to size, depth, presence or absence of infection, and vascular status
      can not be overstated. Proper offloading is vital for those with neuropathic
      lesions. Recognition of patients with a component of ischemia and vascular
      intervention to increase perfusion will aid in wound healing. Of course deep
      infection requires immediate drainage. All efforts of those in the
      multidisciplinary team are directed at the restoration and maintenance of an
      ulcer-free foot which is important in enabling our patients to maintain their
      ambulatory status.

PMID- 16100099
TI  - The Charcot foot: a clinical challenge.
AB  - The Charcot foot (CF) is a clinical challenge. The CF occurs in the presence of
      sensory neuropathy; its etiology and pathogenesis are constantly debated. The aim
      of this short article is to examine therapeutic options from the perspective of
      experienced podiatrists.

PMID- 16100100
TI  - Longitudinal study on the relationship between symptomatology of dementia and
      levels of subjective burden and depression among family caregivers in memory
      clinic patients.
AB  - The objective was to evaluate the course and severity of dementia-related
      symptoms and their relationship to caregivers' subjective burden and depression
      over time. Forty-five patients with dementia and their caregivers were followed
      over a period of 2 years. Patients' cognition, function, and
      behavioral/psychological symptoms were assessed by the Mini Mental State
      Examination, Syndrome Kurz Test, Geriatric Depression Screening scale,
      Instrumental Activities of Daily Living Scale, Physical Self Maintenance Scale,
      Behavioral Abnormalities in Alzheimer's Disease Rating Scale, and Nurses
      Observation Scale for Geriatric Patients. Caregivers' depression and subjective
      burden were evaluated by the Geriatric Depression Screening scale or Beck
      Depression Inventory and the Caregiver Burden Interview. Global dementia
      severity, functional impairment, and behavioral disturbances increased
      significantly over the 2-year observation period. Caregivers' burden remained
      stable, and severe depression decreased over time. There were significant
      associations between burden and dementia-related symptoms. For deficits in
      activities of daily living as well as behavioral disturbances, these associations
      became stronger over time. It was concluded that stage of dementia, functional
      deficits, and behavioral disturbances are important factors when evaluating the
      relationship between patients' symptoms and caregivers' well-being.

PMID- 16100101
TI  - The performance of the Clock Drawing Test in elderly medical inpatients: does it
      have utility in the identification of delirium?
AB  - The Clock Drawing Test is an often-used test for the detection of cognitive
      impairment, but the few studies that have evaluated its utility in delirium have
      produced rather inconsistent results. In a longitudinal study of delirium in
      elderly medical inpatients, we have investigated the relationships between the
      Clock Drawing Test, the presence and severity of delirium, and cognitive
      impairment. Using mixed linear model analysis we found that cognitive impairment
      was the major factor associated with low Clock Drawing Test scores (P < .0001):
      neither the presence nor the severity of delirium had additional significant
      effect on the Clock Drawing Test. Thus, we conclude that although the Clock
      Drawing Test is a good detector of cognitive impairment, it is not a suitable
      tool for detection of delirium in elderly medical inpatients.

PMID- 16100102
TI  - Participation in novelty-seeking leisure activities and Alzheimer's disease.
AB  - The objective was to study the associations between participation in different
      types of mentally stimulating leisure activities and status as Alzheimer's
      disease (AD) case or normal control. Research suggests that participation in
      leisure activities, especially mentally stimulating activities, is associated
      with a lower risk for AD. However, no study has yet evaluated associations
      between AD and different types of mental leisure activities, especially those
      involving "novelty seeking." The authors used a case-control design to compare
      participation in activities across the life span in persons with AD and normal
      controls. Cases (n = 264) were recruited from clinical settings and from the
      community. Controls were drawn from 2 populations. Control group A members (n =
      364) were the friends or neighbors of the cases or members of the same
      organizations to which the cases belonged. Control group B members (n = 181) were
      randomly drawn from the community. The 2 control groups did not differ in their
      responses to most activity questions, so they were combined. Factor analysis of
      activity questions identified 3 activity factors: (1) novelty seeking; (2)
      exchange of ideas; and (3) social. Logistic regression analysis indicated that,
      adjusting for control variables, greater participation in novelty-seeking and
      exchange-of-ideas activities was significantly associated with decreased odds of
      AD. The odds of AD were lower among those who more often participated in
      activities involving exchange of ideas and were lower yet for those who more
      frequently participated in novelty-seeking activities. We conclude that
      participation in a variety of mental activities across the life span may lower
      one's chances of developing AD.

PMID- 16100103
TI  - Delusion of theft and phantom intruder delusion in demented elderly patients in
      Japan.
AB  - Delusion of theft and phantom intruder delusion are among the most frequent
      delusions in dementia. The purpose of this study was to clarify the clinical
      characteristics of patients with these symptoms. The authors conducted a
      questionnaire survey; items included age, gender, dementia diagnosis, cognitive
      function, and activities of daily living. Other clinical characteristics were
      evaluated using the quality of life questionnaire for dementia. A total of 217
      patients with dementia were rated. Frequencies of delusion of theft were as
      follows: frequent, 7%; sometimes, 11%; rare, 16%; and none, 66%. Frequencies of
      phantom intruder delusion were as follows: frequent, 4%; sometimes, 10%; rare,
      9%; and none, 77%. Comparison between positive and negative groups with these
      symptoms revealed that positive groups had higher scores in 2 of 6 domains of the
      quality of life questionnaire for dementia, namely, negative affect and actions,
      and restlessness. The positive group with delusion of theft had higher scores in
      cognitive function and activities of daily living than did the negative group.
      These results suggest that negative affect and action and restlessness might be
      related to delusion of theft or phantom intruder delusion and that delusion of
      theft frequently occurs in the early stage of dementia.

PMID- 16100104
TI  - Cognitive predictors of dementia in Parkinson's disease: a community-based, 4
      year longitudinal study.
AB  - Although mild cognitive impairment and dementia are common and have important
      clinical consequences for patients with Parkinson's disease (PD) and their
      caregivers, it is still unclear whether cognitive symptoms may predict the
      development of dementia in PD patients. The objective of this study was to
      determine whether cognitive deficits in nondemented PD patients predicted the
      development of dementia 4 years later. A total of 76 nondemented PD patients from
      an epidemiological study of PD in the county of Rogaland, Norway, were assessed
      at baseline and 4 years later with neurological, psychiatric, and
      neuropsychological evaluations. Twenty-five (42%) new cases of dementia were
      diagnosed after 4 years. Time to complete the third card of the Stroop test was
      the only variable that was independently associated with dementia. The authors
      concluded that poor performance on a test sensitive to executive dysfunction
      predicted later development of dementia in PD patients. This finding may have
      important clinical implications as a marker of subsequent development of
      dementia.

PMID- 16100105
TI  - Inappropriate sexual behaviors in dementia.
AB  - Dementias are the most common type of neurodegenerative disorder. Behavioral
      disturbances are seen in more than 80% of patients suffering from these
      disorders. Although sexually inappropriate behaviors are not as common as some of
      the other behaviors seen in dementia, they can cause immense distress to all
      those who are affected. There are no randomized trials for the treatment of these
      behaviors, but the available data suggest efficacy for some commonly used
      treatment modalities. In this review, we systematically discuss various aspects
      of these behaviors and available treatments.

PMID- 16100106
TI  - The diagnostic value of cerebrospinal fluid tau protein in dementing and
      nondementing neuropsychiatric disorders.
AB  - Cerebrospinal fluid (CSF) total tau protein (tauT) is increased in Alzheimer's
      disease (AD) and may be of some help in the diagnostic work-up of demented
      patients. The aim of the present study was to investigate the diagnostic aid and
      the additional help (over that of clinical criteria) of tauT in different
      clinical situations. Double-sandwich enzyme-linked immunosorbent assay was used
      to quantify tauT in 61 healthy controls and 241 patients with various
      neuropsychiatric diseases. Our results suggest that CSF tauT offers significant
      additional information over that of clinical criteria of AD, for the
      discrimination of AD from normal aging, depression, synucleinopathy, and possibly
      vascular dementia. However, for the differential diagnosis from frontotemporal
      dementia, corticobasal ganglionic degeneration, and secondary dementia, the
      diagnostic value is inadequate.

PMID- 16100107
TI  - Magnesium and phosphate ions enable NAD binding to methylenetetrahydrofolate
      dehydrogenase-methenyltetrahydrofolate cyclohydrolase.
AB  - The mitochondrial NAD-dependent methylenetetrahydrofolate dehydrogenase
      cyclohydrolase (NMDMC) is believed to have evolved from a trifunctional NADP
      dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase-synthetase. It
      is unique in its absolute requirement for inorganic phosphate and magnesium ions
      to support dehydrogenase activity. To enable us to investigate the roles of these
      ions, a homology model of human NMDMC was constructed based on the structures of
      three homologous proteins. The model supports the hypothesis that the absolutely
      required Pi can bind in close proximity to the 2'-hydroxyl of NAD through
      interactions with Arg166 and Arg198. The characterization of mutants of Arg166,
      Asp190, and Arg198 show that Arg166 is primarily responsible for Pi binding,
      while Arg198 plays a secondary role, assisting in binding and properly orienting
      the ion in the cofactor binding site. Asp190 helps to properly position Arg166.
      Mutants of Asp133 suggest that the magnesium ion interacts with both Pi and the
      aspartate side chain and plays a role in positioning Pi and NAD. NMDMC uses Pi
      and magnesium to adapt an NADP binding site for NAD binding. This adaptation
      represents a novel variation of the classic Rossmann fold.

PMID- 16100108
TI  - Adenylate kinase activity in ABC transporters.

PMID- 16100109
TI  - Phosphorylation of Y14 modulates its interaction with proteins involved in mRNA
      metabolism and influences its methylation.
AB  - The multicomponent exon junction complex (EJC) is deposited on the spliced mRNA
      during pre-mRNA splicing and is implicated in several post-splicing events,
      including mRNA export, nonsense-mediated mRNA decay (NMD), and translation
      control. This report is the first to identify potential post-translational
      modifications of the EJC core component Y14. We demonstrate that Y14 is
      phosphorylated at its repeated arginine/serine (RS) dipeptides, likely by SR
      protein-specific kinases. Phosphorylation of Y14 abolished its interaction with
      EJC components as well as factors that function downstream of the EJC. A non
      phosphorylatable Y14 mutant was equivalent to the wild-type protein with respect
      to its association with spliced mRNA and its ability in NMD activation, but the
      mutant sequestered EJC and NMD factors on ribosome-containing mRNA
      ribonucleoproteins (mRNPs). We therefore hypothesize that phosphorylation of Y14
      occurs upon completion of mRNA surveillance, leading to dissociation of Y14 from
      ribosome-containing mRNPs. Moreover, we found that Y14 is possibly methylated at
      multiple arginine residues in the carboxyl-terminal domain and that methylation
      of Y14 was antagonized by phosphorylation of RS dipeptides. This study reveals
      antagonistic post-translational modifications of Y14 that may be involved in the
      remodeling of Y14-containing mRNPs.

PMID- 16100110
TI  - Alg14 recruits Alg13 to the cytoplasmic face of the endoplasmic reticulum to form
      a novel bipartite UDP-N-acetylglucosamine transferase required for the second
      step of N-linked glycosylation.
AB  - N-linked glycosylation requires the synthesis of an evolutionarily conserved
      lipid-linked oligosaccharide (LLO) precursor that is essential for glycoprotein
      folding and stability. Despite intense research, several of the enzymes required
      for LLO synthesis have not yet been identified. Here we show that two poorly
      characterized yeast proteins known to be required for the synthesis of the LLO
      precursor, GlcNAc2-PP-dolichol, interact to form an unusual hetero-oligomeric UDP
      GlcNAc transferase. Alg13 contains a predicted catalytic domain, but lacks any
      membrane-spanning domains. Alg14 spans the membrane but lacks any sequences
      predicted to play a direct role in sugar catalysis. We show that Alg14 functions
      as a membrane anchor that recruits Alg13 to the cytosolic face of the ER, where
      catalysis of GlcNAc2-PP-dol occurs. Alg13 and Alg14 physically interact and under
      normal conditions, are associated with the ER membrane. Overexpression of Alg13
      leads to its cytosolic partitioning, as does reduction of Alg14 levels.
      Concomitant Alg14 overproduction suppresses this cytosolic partitioning of Alg13,
      demonstrating that Alg14 is both necessary and sufficient for the ER localization
      of Alg13. Further evidence for the functional relevance of this interaction comes
      from our demonstration that the human ALG13 and ALG14 orthologues fail to pair
      with their yeast partners, but when co-expressed in yeast can functionally
      complement the loss of either ALG13 or ALG14. These results demonstrate that this
      novel UDP-GlcNAc transferase is a unique eukaryotic ER glycosyltransferase that
      is comprised of at least two functional polypeptides, one that functions in
      catalysis and the other as a membrane anchor.

PMID- 16100111
TI  - The Saccharomyces cerevisiae Smc2/4 condensin compacts DNA into (+) chiral
      structures without net supercoiling.
AB  - Smc2/4 forms the core of the Saccharomyces cerevisiae condensin, which promotes
      metaphase chromosome compaction. To understand how condensin manipulates DNA, we
      used two in vitro assays to study the role of SMC (structural maintenance of
      chromosome) proteins and ATP in reconfiguring the path of DNA. The first assay
      evaluated the topology of knots formed in the presence of topoisomerase II.
      Unexpectedly, both wild-type Smc2/4 and an ATPase mutant promoted (+) chiral
      knotting of nicked plasmids, revealing that ATP hydrolysis and the non-SMC
      condensins are not required to compact DNA chirally. The second assay measured
      Smc2/4-dependent changes in linking number (Lk). Smc2/4 did not induce (+)
      supercoiling, but instead induced broadening of topoisomer distributions in a
      cooperative manner without altering Lk(0). To explain chiral knotting in
      substrates devoid of chiral supercoiling, we propose that Smc2/4 directs chiral
      DNA compaction by constraining the duplex to retrace its own path. In this highly
      cooperative process, both (+) and (-) loops are sequestered (about one per kb),
      leaving net writhe and twist unchanged while broadening Lk. We have developed a
      quantitative theory to account for these results. Additionally, we have shown at
      higher molar stoichiometries that Smc2/4 prevents relaxation by topoisomerase I
      and nick closure by DNA ligase, indicating that Smc2/4 can saturate DNA. By
      electron microscopy of Smc2/4-DNA complexes, we observed primarily two protein
      laden bound species: long flexible filaments and uniform rings or "doughnuts."
      Close packing of Smc2/4 on DNA explains the substrate protection we observed. Our
      results support the hypothesis that SMC proteins bind multiple DNA duplexes.

PMID- 16100112
TI  - Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA
      topoisomerase.
AB  - Type IIA DNA topoisomerases play multiple essential roles in the management of
      higher-order DNA structure, including modulation of topological state, chromosome
      segregation, and chromatin condensation. These diverse physiologic functions are
      all accomplished through a common molecular mechanism, wherein the protein
      catalyzes transient cleavage of a DNA duplex (the G-segment) to yield a double
      stranded gap through which another duplex (the T-segment) is passed. The overall
      process is orchestrated by the opening and closing of molecular "gates" in the
      topoisomerase structure, which is regulated by ATP binding, hydrolysis, and
      release of ADP and inorganic phosphate. Here we present two crystal structures of
      the ATPase domain of human DNA topoisomerase IIalpha in different nucleotide
      bound states. Comparison of these structures revealed rigid-body movement of the
      structural modules within the ATPase domain, suggestive of the motions of a
      molecular gate.

PMID- 16100113
TI  - Biosynthesis of lipid-linked oligosaccharides in Saccharomyces cerevisiae: Alg13p
      and Alg14p form a complex required for the formation of GlcNAc(2)-PP-dolichol.
AB  - N-Glycosylation in the endoplasmic reticulum is an essential protein modification
      and highly conserved in evolution from yeast to man. Here we identify and
      characterize two essential yeast proteins having homology to bacterial
      glycosyltransferases, designated Alg13p and Alg14p, as being required for the
      formation of GlcNAc(2)-PP-dolichol (Dol), the second step in the biosynthesis of
      the unique lipid-linked core oligosaccharide. Down-regulation of each gene led to
      a defect in protein N-glycosylation and an accumulation of GlcNAc(1)-PP-Dol in
      vivo as revealed by metabolic labeling with [(3)H]glucosamine. Microsomal
      membranes from cells repressed for ALG13 or ALG14, as well as detergent
      solubilized extracts thereof, were unable to catalyze the transfer of N
      acetylglucosamine from UDP-GlcNAc to [(14)C]GlcNAc(1)-PP-Dol, but did not impair
      the formation of GlcNAc(1)-PP-Dol or GlcNAc-GPI. Immunoprecipitating Alg13p from
      solubilized extracts resulted in the formation of GlcNAc(2)-PP-Dol but required
      Alg14p for activity, because an Alg13p immunoprecipitate obtained from cells in
      which ALG14 was down-regulated lacked this activity. In Western blot analysis it
      was demonstrated that Alg13p, for which no well defined transmembrane segment has
      been predicted, localizes both to the membrane and cytosol; the latter form,
      however, is enzymatically inactive. In contrast, Alg14p is exclusively membrane
      bound. Repression of the ALG14 gene causes a depletion of Alg13p from the
      membrane. By affinity chromatography on IgG-Sepharose using Alg14-ZZ as bait, we
      demonstrate that Alg13-myc co-fractionates with Alg14-ZZ. The data suggest that
      Alg13p associates with Alg14p to a complex forming the active transferase
      catalyzing the biosynthesis of GlcNAc(2)-PP-Dol.

PMID- 16100114
TI  - Endoplasmic reticulum-directed Pex3p routes to peroxisomes and restores
      peroxisome formation in a Saccharomyces cerevisiae pex3Delta strain.
AB  - Recent studies on the sorting of peroxisomal membrane proteins challenge the long
      standing model in which peroxisomes are considered to be autonomous organelles
      that multiply by growth and division. Here, we present data lending support to
      the idea that the endoplasmic reticulum (ER) is involved in sorting of the
      peroxisomal membrane protein Pex3p, a protein required early in peroxisome
      biogenesis. First, we show that the introduction of an artificial glycosylation
      site into the N terminus of Pex3p leads to partial N-linked core glycosylation,
      indicative of insertion into the ER membrane. Second, when FLAG-tagged Pex3p is
      equipped with an ER targeting signal, it can restore peroxisome formation in
      pex3Delta cells. Importantly, FLAG antibodies that specifically recognize the
      processed Pex3p show that the signal peptide of the fusion protein is efficiently
      cleaved off and that the processed protein localizes to peroxisomes. In contrast,
      a Pex3p construct in which cleavage of the signal peptide is blocked by a
      mutation localizes to the ER and the cytosol and cannot complement pex3Delta
      cells. Together, these results strongly suggest that ER-targeted Pex3p indeed
      routes via the ER to peroxisomes, and we hypothesize that this pathway is also
      used by endogenous Pex3p.

PMID- 16100115
TI  - Independent regulation of Hsp70 and Hsp90 chaperones by Hsp70/Hsp90-organizing
      protein Sti1 (Hop1).
AB  - Hsp70 and Hsp90 protein chaperones cooperate in a protein-folding pathway
      required by many "client" proteins. The co-chaperone Sti1p coordinates functions
      of Hsp70 and Hsp90 in this pathway. Sti1p has three tetratricopeptide repeat
      (TPR) domains. TPR1 binds Hsp70, TPR2a binds Hsp90, and the ligand for TPR2b is
      unknown. Although Sti1p is thought to be dedicated to the client folding pathway,
      we earlier showed that Sti1p regulated Hsp70, independently of Hsp90, in a way
      that impairs yeast [PSI+] prion propagation. Using this prion system to monitor
      Sti1p regulation of Hsp70 and an Hsp90-inhibiting compound to monitor Hsp90
      regulation, we identified Sti1p mutations that separately affect Hsp70 and Hsp90.
      TPR1 mutations impaired Sti1p regulation of Hsp70, but deletion of TPR2a and
      TPR2b did not. Conversely, TPR2a and TPR2b mutations impaired Sti1p regulation of
      Hsp90, but deletion of TPR1 did not. All Sti1p mutations variously impaired the
      client folding pathway, which requires both Hsp70 and Hsp90. Thus, Sti1p
      regulated Hsp70 and Hsp90 separately, Hsp90 is implicated as a TPR2b ligand, and
      mutations separately affecting regulation of either chaperone impair a pathway
      that is dependent upon both. We further demonstrate that client folding depended
      upon bridging of Hsp70 and Hsp90 by Sti1p and find conservation of the
      independent regulation of Hsp70 and Hsp90 by human Hop1.

PMID- 16100116
TI  - APBP-1, a DNA/RNA-binding protein, interacts with the chick aggrecan regulatory
      region.
AB  - Expression of the extracellular proteoglycan aggrecan is both cell-specific and
      developmentally regulated. Previous studies identified six functionally defined
      cis elements in the aggrecan promoter region which were shown to repress aggrecan
      gene expression (1). Using competition electrophoretic mobility shift assays
      (EMSAs) we have now identified in nuclear extracts a functional repressor cis
      element, (T/C)TCCCCT(A/C)RRC, which occurs at multiple locations within the chick
      aggrecan regulatory region. We purified the factor that binds to this cis element
      and established that it, APBP-1 (aggrecan promoter-binding protein-1), is a 19
      kDa protein that has significant homology to CIRP (cold inducible RNA-binding
      protein). Recombinantly expressed APBP-1 mimics the native cis element-trans
      factor interaction in EMSAs. In situ hybridization demonstrates that aggrecan and
      APBP-1 RNA expression are restricted to complementary tissues in the developing
      limb, and Northern blot analysis of chick limb bud mRNA shows that APBP-1 mRNA
      expression is inversely correlated with aggrecan mRNA expression. Functional
      analyses by transient transfections and Northern blot analyses suggest APBP-1 has
      the capacity to repress aggrecan expression, indicating that this factor may be
      important regulator of aggrecan gene expression.

PMID- 16100117
TI  - Glucocorticoids regulate transcription of the gene for phosphoenolpyruvate
      carboxykinase in the liver via an extended glucocorticoid regulatory unit.
AB  - The hepatic transcriptional regulation by glucocorticoids of the cytosolic form
      of phosphoenolpyruvate carboxykinase (PEPCK-C) gene is coordinated by
      interactions of specific transcription factors at the glucocorticoid regulatory
      unit (GRU). We propose an extended GRU that consists of four accessory sites, two
      proximal AF1 and AF2 sites and their distal counterpart dAF1 (-993) and a new
      site, dAF2 (-1365); together, these four sites form a palindrome. Sequencing and
      gel shift binding assays of hepatic nuclear proteins interacting with these sites
      indicated similarity of dAF1 and dAF2 sites to the GRU proximal AF1 and AF2
      sites. Chromatin immunoprecipitation assays demonstrated that glucocorticoids
      enhanced the binding of FOXO1 and peroxisome proliferator-activated receptor
      alpha to AF2 and dAF2 sites and not to dAF1 site but enhanced the binding of
      hepatic nuclear transcription factor-4alpha only to the dAF1 site. Insulin
      inhibited the binding of these factors to their respective sites but intensified
      the binding of phosphorylated FOXO1. Transient transfections in HepG2 human
      hepatoma cells showed that glucocorticoid receptor interacts with several non
      steroid nuclear receptors, yielding a synergistic response of the PEPCK-C gene
      promoter to glucocorticoids. The synergistic stimulation by glucocorticoid
      receptor together with peroxisome proliferator-activated receptor-alpha or
      hepatic nuclear transcription factor-4alpha requires all four accessory sites,
      i.e. a mutation of each of these markedly affects the synergistic response. Mice
      with a targeted mutation of the dAF1 site confirmed this requirement. This
      mutation inhibited the full response of hepatic PEPCK-C gene to diabetes by
      reducing PEPCK-C mRNA level by 3.5-fold and the level of circulating glucose by
      25%.

PMID- 16100118
TI  - Improved photobiological H2 production in engineered green algal cells.
AB  - Oxygenic photosynthetic organisms use solar energy to split water (H2O) into
      protons (H+), electrons (e-), and oxygen. A select group of photosynthetic
      microorganisms, including the green alga Chlamydomonas reinhardtii, has evolved
      the additional ability to redirect the derived H+ and e- to drive hydrogen (H2)
      production via the chloroplast hydrogenases HydA1 and A2 (H2 ase). This process
      occurs under anaerobic conditions and provides a biological basis for solar
      driven H2 production. However, its relatively poor yield is a major limitation
      for the economic viability of this process. To improve H2 production in
      Chlamydomonas, we have developed a new approach to increase H+ and e- supply to
      the hydrogenases. In a first step, mutants blocked in the state 1 transition were
      selected. These mutants are inhibited in cyclic e- transfer around photosystem I,
      eliminating possible competition for e- with H2ase. Selected strains were further
      screened for increased H2 production rates, leading to the isolation of Stm6.
      This strain has a modified respiratory metabolism, providing it with two
      additional important properties as follows: large starch reserves (i.e. enhanced
      substrate availability), and a low dissolved O2 concentration (40% of the wild
      type (WT)), resulting in reduced inhibition of H2ase activation. The H2
      production rates of Stm6 were 5-13 times that of the control WT strain over a
      range of conditions (light intensity, culture time, +/- uncoupler). Typically,
      approximately 540 ml of H2 liter(-1) culture (up to 98% pure) were produced over
      a 10-14-day period at a maximal rate of 4 ml h(-1) (efficiency = approximately 5
      times the WT). Stm6 therefore represents an important step toward the development
      of future solar-powered H2 production systems.

PMID- 16100119
TI  - Binding and functions of ADP-ribosylation factor on mammalian and yeast
      peroxisomes.
AB  - We have analyzed in vitro the binding characteristics of members of the ADP
      ribosylation factor (ARF) family of proteins to a highly purified rat liver
      peroxisome preparation void of Golgi membranes and studied in vivo a role these
      proteins play in the proliferation of yeast peroxisomes. Although both ARF1 and
      ARF6 were found on peroxisomes, coatomer recruitment only depended on ARF1-GTP.
      Recruitment of ARF1 and coatomer to peroxisomes was significantly affected both
      by pretreating the animals with peroxisome proliferators and by ATP and a
      cytosolic fraction designated the intermediate pool fraction depleted of ARF and
      coatomer. In the presence of ATP, the concentrations of ARF1 and coatomer on
      peroxisomes were reduced, whereas intermediate pool fraction led to a
      concentration-dependent decrease in ARF and increase in coatomer. Brefeldin A, a
      fungal toxin that is known to reduce ARF1 binding to Golgi membranes, did not
      affect ARF1 binding to peroxisomes. In Saccharomyces cerevisiae, both ScARF1 and
      ScARF3, the yeast orthologs of mammalian ARF1 and ARF6, were implicated in the
      control of peroxisome proliferation. ScARF1 regulated this process in a positive
      manner, and ScARF3 regulated it in a negative manner.

PMID- 16100120
TI  - LASS5 is a bona fide dihydroceramide synthase that selectively utilizes palmitoyl
      CoA as acyl donor.
AB  - We demonstrated recently (Riebeling, C., Allegood, J.C., Wang, E., Merrill, A. H.
      Jr., and Futerman, A. H. (2003) J. Biol. Chem. 278, 43452-43459) that upon over
      expression in human embryonic kidney cells, longevity assurance gene homolog 5
      (LASS5, previously named TRH4) elevates the synthesis of (dihydro)ceramides
      selectively enriched in palmitic acid. To determine whether LASS5 is a bona fide
      dihydroceramide synthase or, alternatively, whether it modifies an endogenous
      dihydroceramide synthase, we over-expressed LASS5 with a hemagglutinin (HA) tag
      at the C terminus, solubilized it using digitonin, and purified it by
      immunoprecipitation. Solubilized LASS5-HA displays the same fatty acid
      selectivity as the membrane-bound enzyme. After elution from agarose beads, only
      one band could be detected by SDS-PAGE, and its identity was confirmed to be
      LASS5 by mass spectrometry. Dihydroceramide synthase activity of the eluted LASS5
      HA protein was totally dependent on exogenously added phospholipids. Moreover,
      eluted LASS5-HA was highly selective toward palmitoyl-CoA as acyl donor and was
      inhibited by the (dihydro)ceramide synthase inhibitor, fumonisin B1. This study
      identifies LASS5 as a genuine dihydroceramide synthase and demonstrates that
      mammalian dihydroceramide synthases do not require additional subunits for their
      activity.

PMID- 16100121
TI  - Cyclopentenone isoprostanes inhibit the inflammatory response in macrophages.
AB  - Although both inflammation and oxidative stress contribute to the pathogenesis of
      many disease states, the interaction between the two is poorly understood.
      Cyclopentenone isoprostanes (IsoPs), highly reactive structural isomers of the
      bioactive cyclopentenone prostaglandins PGA2 and PGJ2, are formed non
      enzymatically as products of oxidative stress in vivo. We have, for the first
      time, examined the effects of synthetic 15-A2- and 15-J2-IsoPs, two groups of
      endogenous cyclopentenone IsoPs, on the inflammatory response in RAW264.7 and
      primary murine macrophages. Cyclopentenone IsoPs potently inhibited
      lipopolysaccharide-stimulated IkappaB alpha degradation and subsequent NF-kappaB
      nuclear translocation and transcriptional activity. Expression of inducible
      nitric-oxide synthase and cyclooxygenase-2 were also inhibited by cyclopentenone
      IsoPs as was nitrite and prostaglandin production (IC50 approximately 360 and 210
      nM, respectively). 15-J2-IsoPs potently activated peroxisome proliferator
      activated receptor gamma (PPARgamma) nuclear receptors, whereas 15-A2-IsoP did
      not, although the anti-inflammatory effects of both molecules were PPARgamma
      independent. Interestingly 15-A2-IsoPs induced oxidative stress in RAW cells that
      was blocked by the antioxidant 4-hydroxy-TEMPO (TEMPOL) or the mitochondrial
      uncoupler carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone. TEMPOL also
      abrogated the inhibitory effect of 15-A2-IsoPs on lipopolysaccharide-induced NF
      kappaB activation, inducible nitricoxide synthase expression, and nitrite
      production, suggesting that 15-A2-IsoPs inhibit the NF-kappaB pathway at least
      partially via a redox-dependent mechanism. 15-J2-IsoP, but not 15-A2-IsoP, also
      potently induced RAW cell apoptosis again via a PPAR gamma-independent mechanism.
      These findings suggest that cyclopentenone IsoPs may serve as negative feedback
      regulators of inflammation and have important implications for defining the role
      of oxidative stress in the inflammatory response.

PMID- 16100122
TI  - Oxidative stress is responsible for mitochondrial permeability transition
      induction by salicylate in liver mitochondria.
AB  - The interaction of salicylate with the respiratory chain of liver mitochondria
      generates hydrogen peroxide and, most probably, other reactive oxygen species,
      which in turn oxidize thiol groups and glutathione. This oxidative stress,
      confirmed by the prevention of action by antioxidant agents, leads to the
      induction of the mitochondrial permeability transition in the presence of Ca2+.
      This phenomenon induces further increase of oxidative damage resulting in
      impairment of oxidative phosphorylation and beta-oxidation, cardinal features of
      Reye's syndrome in the liver. Mitochondrial permeability transition induction
      also induces the release of cytochrome c and apoptotic inducing factor from
      mitochondria, suggesting that salicylate also behaves as a pro-apoptotic agent.
      The reactive group of salicylate for inducing oxidative stress is the hydroxyl
      group which, by interacting with a Fe-S cluster of mitochondrial Complex I, the
      so-called N-2(Fe-S) center, produces reactive oxygen species.

PMID- 16100124
TI  - Sedation and neuromuscular blockade in the ICU.

PMID- 16100125
TI  - Temporal changes in clinical outcomes with ARDS.

PMID- 16100126
TI  - Weaning and respiratory muscle dysfunction: the egg-chicken dilemma.

PMID- 16100127
TI  - Acute and chronic respiratory failure in patients with obesity-hypoventilation
      syndrome: a new challenge for noninvasive ventilation.

PMID- 16100128
TI  - Bariatric surgery for obstructive sleep apnea.

PMID- 16100129
TI  - Einthoven's machine, alive and well.

PMID- 16100130
TI  - Risk of catheter-related bloodstream infection with peripherally inserted central
      venous catheters used in hospitalized patients.
AB  - BACKGROUND: Peripherally inserted central venous catheters (PICCs) are now widely
      used for intermediate and long-term access in current-day health care, especially
      in the inpatient setting, where they are increasingly supplanting conventional
      central venous catheters (CVCs) placed percutaneously into the internal jugular,
      subclavian, or femoral veins. Data on the risk of PICC-related bloodstream
      infection (BSI) with PICCs used in hospitalized patients are limited. STUDY
      OBJECTIVES: To determine the risk of PICC-related BSI in hospitalized patients.
      STUDY DESIGN: Prospective cohort study using data from two randomized trials
      assessing the efficacy of chlorhexidine-impregnated sponge dressing and
      chlorhexidine for cutaneous antisepsis. METHODS: PICCs inserted into the
      antecubital vein in two randomized trials during from 1998 to 2000 were
      prospectively studied; most patients were in an ICU. PICC-related BSI was
      confirmed in each case by demonstrating concordance between isolates colonizing
      the PICC at the time of removal and from blood cultures by restriction-fragment
      DNA subtyping. RESULTS: Overall, 115 patients had 251 PICCs placed. Mean duration
      of catheterization was 11.3 days (total, 2,832 PICC-days); 42% of the patients
      were in an ICU at some time, 62% had urinary catheters, and 49% had received
      mechanical ventilation. Six PICC-related BSIs were identified (2.4%), four with
      coagulase-negative staphylococcus, one with Staphylococcus aureus, and one with
      Klebsiella pneumoniae, a rate of 2.1 per 1,000 catheter-days. CONCLUSION: This
      prospective study shows that PICCs used in high-risk hospitalized patients are
      associated with a rate of catheter-related BSI similar to conventional CVCs
      placed in the internal jugular or subclavian veins (2 to 5 per 1,000 catheter
      days), much higher than with PICCs used exclusively in the outpatient setting
      (approximately 0.4 per 1,000 catheter-days), and higher than with cuffed and
      tunneled Hickman-like CVCs (approximately 1 per 1,000 catheter-days). A
      randomized trial of PICCs and conventional CVCs in hospitalized patients
      requiring central access is needed. Our data raise the question of whether the
      growing trend in many hospital hematology and oncology services to switch from
      use of cuffed and tunneled CVCs to PICCs is justified, particularly since PICCs
      are more vulnerable to thrombosis and dislodgment, and are less useful for
      drawing blood specimens. Moreover, PICCs are not advisable in patients with renal
      failure and impending need for dialysis, in whom preservation of upper-extremity
      veins is needed for fistula or graft implantation.

PMID- 16100131
TI  - Use of sedatives and neuromuscular blockers in a cohort of patients receiving
      mechanical ventilation.
AB  - OBJECTIVE: To describe the use of sedatives and neuromuscular blocking agents
      (NMBs) and their impact in outcome in an international cohort of patients
      receiving mechanical ventilation. METHODS: We analyzed the database of a
      prospective, multicenter cohort of 5,183 adult patients who received mechanical
      ventilation for > 12 h. We considered that a patient received a given agent when
      it was administered for at least 3 h in a 24-h period. RESULTS: A total of 3,540
      patients (68%; 95% confidence interval [CI], 67 to 69%) received a sedative at
      any time while receiving mechanical ventilation. The median number of days of use
      was 3 (interquartile range [IQR], 2 to 6 days). The persistent use of sedative
      was associated with more days of mechanical ventilation (median, 4 days [IQR, 2
      to 8 days], vs 3 days [IQR, 2 to 4 days] in patients who did not receive
      sedatives [p < 0.001]); more weaning days (median, 2 days [IQR, 1 to 3 days], vs
      2 days [IQR, 1 to 5 days] in patients who did not receive sedatives [p < 0.001]);
      and longer length of stay in the ICU (median, 8 days [IQR, 5 to 15 days], vs 5
      days [IQR, 3 to 9 days] in patients who did not receive sedatives [p < 0.001]).
      Six hundred eighty-six patients (13%; 95% CI, 12 to 14%) received an NMB for at
      least 1 day. The median number of days of use was 2 (IQR, 1 to 4 days). The
      administration of an NMB was independently related with age, a normal previous
      functional status, main reason of mechanical ventilation (patients with ARDS
      received more NMBs), and with patient management (patients requiring permissive
      hypercapnia, prone position, high level of positive end-expiratory pressure, and
      high airways pressure). CONCLUSIONS: The use of sedatives is very common, and
      their use is associated with a longer duration of mechanical ventilation, weaning
      time, and stay in the ICU. NMBs are used in 13% of the patients and are
      associated with longer duration of mechanical ventilation, weaning time, stay in
      the ICU, and higher mortality.

PMID- 16100132
TI  - Trial of a disease management program to reduce hospital readmissions of the
      chronically critically ill.
AB  - BACKGROUND: Patients requiring prolonged periods of intensive care and mechanical
      ventilation are termed chronically critically ill. They are prone to continued
      morbidity and mortality after hospital discharge and are at high risk for
      hospital readmission. Disease management (DM) programs have been shown to be
      effective in improving both coordination and efficiency of care after hospital
      discharge for populations with single-disease diagnoses, but have not been tested
      with patients with multiple-disease diagnoses, such as the chronically critically
      ill. STUDY OBJECTIVES: To test the effect of a DM program on hospital readmission
      patterns of chronically critically ill patients during the first 2 months after
      hospital discharge and to estimate the cost-effectiveness of the DM program.
      DESIGN: Randomized, controlled trial. SETTING: Academic medical center, extended
      care facilities, and participant homes. PARTICIPANTS: Three hundred thirty-four
      consenting adults from one academic medical center who underwent > 3 days of
      mechanical ventilation and survived to hospital discharge. INTERVENTION: Two
      hundred thirty-one patients in the experimental group received care coordination,
      family support, teaching, and monitoring of therapies from a team of advanced
      practice nurses, a geriatrician, and a pulmonologist for 2 months post-hospital
      discharge. MEASUREMENTS: Rehospitalization rate, time-to-first rehospitalization,
      duration of rehospitalization, mortality during rehospitalization, and associated
      costs. RESULTS: Patients who received DM services had significantly fewer mean
      days of rehospitalization (11.4; 95% confidence interval [CI], 9.3 to 12.6)
      compared with the control group (16.7 days; 95% CI, 12.5 to 21.0; p = 0.03).
      There were no other significant differences between experimental and control
      groups, although all measures of rehospitalization risk for the experimental
      group were in a positive direction. Total cost savings associated with the
      intervention were approximately $481,811 for the 93 subjects who were readmitted
      to the hospital. CONCLUSIONS: Chronic critical illness may have a natural
      trajectory of continued morbidity following hospital discharge that is not
      affected by the provision of additional care coordination services. Nevertheless,
      given the high cost of rehospitalization and the additional burden it imposes on
      patients and families, interventions that can reduce the duration of
      rehospitalization are cost-effective and merit continued testing.

PMID- 16100133
TI  - In-hospital and 5-year mortality of patients treated in the ICU for acute
      exacerbation of COPD: a retrospective study.
AB  - STUDY OBJECTIVES: The prognosis of patients with COPD requiring admission to the
      ICU is generally believed to be poor. There is a paucity of long-term survival
      data. We undertook a study to examine both the in-hospital and 5-year mortality
      rates and to identify the clinical predictors of these outcomes. DESIGN: We
      conducted a retrospective cohort study of 57 patients admitted to the ICU between
      January 1999 and December 2000 for acute respiratory failure attributable to
      COPD. RESULTS: The mean (+/-SD) age of the study population was 70 +/- 8 years.
      More than 90% of patients required intubation, and the mean duration of
      mechanical ventilation (MV) was 2.3 +/- 2.2 days. The in-hospital mortality rate
      for the entire cohort was 24.5%. The mortality rates at 6 months and 1, 3, and 5
      years were 39.0%, 42.7%, 61.2%, and 75.9%, respectively, following admission to
      the ICU. The median survival time for all patients was 26 months. The mortality
      rate at 5 years was 69.6% for patients who were discharged alive from the
      hospital. Using multivariate analysis, hospital mortality correlated positively
      with age, previous history of MV, long-term use of oral corticosteroids, ICU
      admission albumin level, APACHE (acute physiology and chronic health evaluation)
      II score, and duration of hospitalization. No factors predictive of mortality at
      5 years were identified. CONCLUSIONS: We support previous findings of good early
      survival and significant but acceptable long-term mortality rates in patients who
      have been admitted to the ICU for acute exacerbation of COPD. Increased age,
      previous history of MV, poor nutritional status, and higher APACHE II score on
      ICU admission could be identified as risk factors associated with increased
      mortality rates. Long-term survival of patients with COPD who required MV for an
      acute exacerbation of their disease cannot be predicted simply from data
      available at the time of intubation. Physicians should incorporate these factors
      in their decision-making process.

PMID- 16100134
TI  - Causes and timing of death in patients with ARDS.
AB  - BACKGROUND: Since the early 1980s, case fatality of patients with ARDS has
      decreased, and explanations are unclear. DESIGN AND METHODS: Using identical
      definitions of ARDS and organ failure, we analyzed consecutive cohorts of
      patients meeting syndrome criteria at our institution in 1982 (n = 46), 1990 (n =
      112), 1994 (n = 99), and 1998 (n = 205) to determine causes and timing of death.
      RESULTS: Overall case fatality has decreased from 68% in 1981-1982 to a low of
      29% in 1996, plateauing since the mid-1990s (p = 0.001 for trend). Sepsis
      syndrome with multiple organ failure remains the most common cause of death (30
      to 50%), while respiratory failure causes a small percentage (13 to 19%) of
      deaths. The distribution of causes of death has not changed over time. There was
      no change in the timing of death during the study periods: 26 to 44% of deaths
      occurred early (< 72 h after ARDS onset), and 56 to 74% occurred late (> 72 h
      after ARDS onset). However, the increased survival over the past 2 decades is
      entirely accounted for by patients who present with trauma and other risk factors
      for their ARDS, while survival for those patients whose risk factor is sepsis has
      not changed. Additionally, withdrawal of life support in these patients is now
      occurring at our institution significantly more frequently than in the past, and
      median time until death has decreased in patients who have support withdrawn.
      CONCLUSIONS: While these results do not explain the overall case fatality decline
      in ARDS, they do indicate that sepsis syndrome remains the leading cause of death
      and suggest that future therapies to improve survival be targeted at reducing the
      complications of sepsis.

PMID- 16100135
TI  - Contribution of blinded, protected quantitative specimens to the diagnostic and
      therapeutic management of ventilator-associated pneumonia.
AB  - OBJECTIVE: Sampling techniques for microbiological diagnosis of ventilator
      associated pneumonia (VAP) remain debated, and it is unclear to what extent
      invasive diagnostic techniques impact the management of patients. DESIGN: A
      prospective observational study of 68 first episodes of suspected pneumonia in
      which specimens were obtained blindly (endotracheal aspirate [EA] and blinded
      protected telescoping catheter [PTC]) and via bronchoscopy (directed PTC
      bronchoscopy and BAL), and in sequence, and the results were provided to the
      attending physicians in the same order. Therapeutic plans resulting at each step
      were examined, and their adequacy was assessed using quantitative BAL fluid
      culture as the diagnostic standard. PARTICIPANTS: Sixty-eight patients with
      clinically suspected VAP hospitalized in two ICUs in a tertiary care university
      hospital. RESULTS: There were 35 patients (51%) with VAP confirmed by BAL fluid
      culture (13 early onset and 22 late onset). EA specimens grew organisms (light
      growth or more) in all BAL-confirmed VAP cases and 59% of nonconfirmed cases,
      whereas the sensitivity and specificity of blinded PTC quantitative cultures were
      77% and 97%, and did not differ from those of directed PTC cultures (77% and 94%,
      respectively). Antibiotic therapy based on the clinical severity and likelihood
      of VAP, Gram stain results, and early blinded PTC culture results was adequate in
      54% (19 of 35 VAP patients) within 2 h of sampling and 80% (28 of 35 patients)
      within 24 h; therapy was revised in only 3 more patients following BAL culture
      results. New antibiotics were introduced within the first 24 h in 14 of 33
      nonconfirmed episodes (42%), and antibiotics were withheld or withdrawn within 48
      h in 23 episodes (70%); three of these patients-with both blinded PTC and BAL
      growing organisms below the threshold-had early subsequently confirmed pneumonia
      with the same organism. CONCLUSIONS: A therapeutic approach guided by
      quantitative cultures of blinded specimens helps achieve early adequate
      management of approximately 90% of patients suspected of having VAP.

PMID- 16100136
TI  - Penetration of gentamicin into the alveolar lining fluid of critically ill
      patients with ventilator-associated pneumonia.
AB  - STUDY OBJECTIVES: To estimate the penetration of gentamicin into lung tissue by
      measuring its concentrations in alveolar lining fluid (ALF) and blood in
      critically ill patients with ventilator-associated pneumonia (VAP). PATIENTS AND
      INTERVENTIONS: The study population consisted of 24 patients who were admitted to
      an ICU for respiratory failure and developed VAP. Patients were scheduled to
      undergo bronchoscopy with BAL after IV administration of a once-daily, 240-mg
      schedule of gentamicin for the treatment of VAP. Patients were assigned at random
      to one of four groups of six patients each according to the scheduled time for
      bronchoscopy (1, 2, 4, or 6 h, respectively). A serum sample was obtained at 0.5
      h (n = 24), and both serum and ALF samples (n = 6) were collected at each of the
      above specified times for measurement of antibiotic concentrations. MEASUREMENTS
      AND RESULTS: Mean +/- SEM gentamicin concentrations in the ALF were 2.95 +/-
      0.37, 4.24 +/- 0.42, 3.10 +/- 0.39, and 2.65 +/- 0.35 microg/mL at 1, 2, 4, and 6
      h, respectively, after the start of antibiotic infusion. Maximum gentamicin
      concentrations in serum (13.39 +/- 0.91 mug/mL, n = 24) and ALF (4.24 +/- 0.42
      microg/mL, n = 6) were achieved at 0.5 h and 2 h, respectively, giving a
      penetration ratio of 0.32. The mean ratios of ALF/serum concentrations between 1
      h and 6 h ranged from 0.30 to 1.14. After completion of the distribution phase, a
      significant positive correlation (p = 0.02) was found between gentamicin
      concentrations in the serum and ALF. CONCLUSIONS: Once-daily IV administration of
      240-mg gentamicin achieved average peak antibiotic concentrations of 4.24
      microg/mL in the ALF 2 h after administration, and an ALF/serum penetration ratio
      of 32%. Higher gentamicin doses to produce higher peak blood levels than those
      found with the study dose are necessary to obtain active alveolar concentrations
      against less sensitive microorganisms in the treatment of VAP in ICU patients.

PMID- 16100137
TI  - Reduced inspiratory muscle endurance following successful weaning from prolonged
      mechanical ventilation.
AB  - STUDY OBJECTIVES: Respiratory muscle weakness and decreased endurance have been
      demonstrated following mechanical ventilation. However, its relationship to the
      duration of mechanical ventilation is not known. The aim of this study was to
      assess respiratory muscle endurance and its relationship to the duration of
      mechanical ventilation. DESIGN: Prospective study. SETTING: Tertiary teaching
      hospital ICU. PATIENTS: Twenty subjects were recruited for the study who had
      received mechanical ventilation for > or = 48 h and had been discharged from the
      ICU. MEASUREMENTS: FEV1, FVC, and maximal inspiratory pressure (P(I(max)) at
      functional residual capacity were recorded. The P(I(max)) attained following
      resisted inspiration at 30% of the initial P(I(max)) for 2 min was recorded, and
      the fatigue resistance index (FRI) [P(I(max)) final/P(I(max))initial] was
      calculated. The duration of ICU length of stay (ICULOS), duration of mechanical
      ventilation (MVD), duration of weaning (WD), and Charlson comorbidities score
      (CCS) were also recorded. Relationships between fatigue and other parameters were
      analyzed using the Spearman correlations (rho). RESULTS: Subjects were admitted
      to the ICU for a mean duration of 7.7 days (SD, 3.7 days) and required mechanical
      ventilation for a mean duration of 4.6 days (SD, 2.5 days). The mean FRI was 0.88
      (SD, 0.13), indicating a 12% fall in P(I(max)), and was negatively correlated
      with MVD (r = -0.65; p = 0.007). No correlations were found between the FRI and
      FEV1, FVC, ICULOS, WD, or CCS. CONCLUSIONS: Patients who had received mechanical
      ventilation for > 48 h have reduced inspiratory muscle endurance that worsens
      with the duration of mechanical ventilation and is present following successful
      weaning. These data suggest that patients needing prolonged mechanical
      ventilation are at risk of respiratory muscle fatigue and may benefit from
      respiratory muscle training.

PMID- 16100138
TI  - The drive to survive: unplanned extubation in the ICU.
AB  - STUDY OBJECTIVES: To assess the consequences of unplanned extubation (UE) in the
      ICU. DESIGN: Case-control study. SETTING: Fourteen-bed, medical-surgical ICU of a
      university-affiliated community teaching hospital. PATIENTS: One hundred patients
      who underwent UE compared to 200 control patients who underwent mechanical
      ventilation (MV) without UE between January 1, 1999, and June 30, 2004.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients with UE had longer ICU
      and hospital length of stay (LOS) and longer duration of MV than did control
      subjects. Hospital mortality was 20% among UE and 35% among control patients (p =
      0.011). Of the 100 patients with UE, reintubation within 48 h (UE R+) was
      required in 44 patients and no reintubation within 48 h (UE R-) was required in
      56 patients. ICU and hospital LOS; duration of MV; rate of ICU-acquired
      infections; ICU pharmacy, laboratory and diagnostic imaging charges; and
      mortality were all much higher among UE R+ patients than among UE R- patients.
      Multiple logistic regression analysis revealed that age was the only predictor of
      the need for reintubation after UE and that age and the need for reintubation
      were the only predictors of mortality after UE. CONCLUSIONS: UE was associated
      with increased hospital and ICU LOS but decreased mortality in this heterogeneous
      population of critically ill adult patients. These findings were entirely
      explained by the divergent outcomes of the UE R+ and UE R- groups. Patients with
      UE who did not require reintubation had remarkably good outcomes. It remains
      incumbent on ICU teams to institute protocols for regular identification of
      patients ready to be liberated from MV.

PMID- 16100139
TI  - Intensivist-to-bed ratio: association with outcomes in the medical ICU.
AB  - OBJECTIVE: With an increasing number of critical care beds, a shortage of
      critical care physicians, and pressure from purchasers, there is a need to define
      the optimal intensivist-to-ICU bed ratio. The objective of this study was to
      determine if there are any associations between the intensivist-to-ICU bed ratio
      and the outcome of patients admitted to the medical ICU. DESIGN: Retrospective
      cohort study. SETTING: A tertiary care medical center. PATIENTS: All critically
      ill patients admitted to a medical ICU between December 8, 2001, and July 14,
      2003. INTERVENTIONS: None. MEASUREMENTS: Demographics, APACHE (acute physiology
      and chronic health evaluation) III-predicted mortality, ICU length of stay (LOS),
      hospital LOS, and ICU and hospital mortality rates. Four time periods based on
      intensivist-to-ICU bed ratios of 1:7.5, 1:9.5, 1:12, and 1:15 were identified.
      Regression analyses were performed to develop customized models to predict ICU
      and hospital LOS and mortality. The ICU LOS ratio, defined as the ratio of the
      observed to predicted LOS, and standardized mortality ratio (SMR) were calculated
      for each of the four periods. RESULTS: A total of 2,492 patients were included in
      the study. There was no difference in the severity of illness at the time of ICU
      admission among the four periods. The mean ICU LOS ratio was longer for an
      intensivist-to-ICU bed ratio of 1:15 compared to the other periods. The ICU and
      hospital SMR did not differ significantly among the four periods. CONCLUSION:
      Differences in intensivist-to-ICU bed ratios, ranging from 1:7.5 to 1:15, were
      not associated with differences in ICU or hospital mortality. However, a ratio of
      1:15 was associated with increased ICU LOS.

PMID- 16100140
TI  - Acute respiratory failure due to pneumocystis pneumonia in patients without human
      immunodeficiency virus infection: outcome and associated features.
AB  - OBJECTIVE: To examine outcome and associated factors of acute respiratory failure
      (ARF) in non-HIV-related Pneumocystis pneumonia (PCP) in patients admitted to a
      medical ICU between 1995 and 2002. DESIGN: A retrospective review of medical
      records and an APACHE (acute physiology and chronic health evaluation) III
      database. SETTING: Academic tertiary medical center. RESULTS: We identified 30
      patients with non-HIV-related PCP and ARF. In-hospital, 6-month, and 1-year
      mortality rates were 67%, 77%, and 80%, respectively. Median age was 63.5 years.
      Median APACHE III score on day 1 was 65.5. Median ICU and hospital lengths of
      stay were 13 days and 21 days, respectively. All seven patients having a
      pneumothorax died. All but one patient had an elevated lactate dehydrogenase
      level (median, 563 U/L). The diagnosis was made using BAL in 28 patients and by
      transbronchial biopsy in the remaining 2 patients. All patients were
      immunosuppressed (eight were receiving corticosteroids, seven were receiving
      chemotherapy, and the remainder received both). Median immunosuppressive
      prednisone-equivalent dose was 40 mg (median length of treatment, 4.5 months).
      Not a single patient received PCP prophylaxis. All but one patient required
      intubation and invasive positive pressure ventilation (PPV). Hospital mortality
      was associated with high APACHE III scores on day 1 (p = 0.05), intubation delay
      (p = 0.03), length of PPV (p = 0.003), and development of pneumothorax (p =
      0.033). Logistic regression analysis demonstrated that association of intubation
      delay with hospital mortality persisted after adjusting for severity of illness
      (p = 0.03). CONCLUSIONS: Among patients with ARF secondary to non-HIV-related
      PCP, poor prognostic factors include high APACHE III scores, intubation delay,
      longer duration of PPV, and development of pneumothorax. None of the patients in
      this series received PCP prophylaxis prior to the development of pneumonia.

PMID- 16100141
TI  - Goal-directed therapy of cardiac preload in induced whole-body hyperthermia.
AB  - OBJECTIVES: To optimize volume therapy during induced whole-body hyperthermia
      (WBH) < or = 42.2 degrees C, pulmonary capillary wedge pressure (PCWP) and
      intrathoracic blood volume index (ITBVI) were compared as goal parameters.
      DESIGN: Prospective clinical study. SETTING: ICU at university hospital.
      PATIENTS: Twenty-three patients with metastatic cancers. INTERVENTIONS: Radiant
      WBH in combination with induced hyperglycemia, hyperoxemia, and chemotherapy was
      applied. Volume therapy was directed to the PCWP (group A, 8 to 12 mm Hg [20
      treatments]), or to ITBVI (group B, 800 to 1,100 mL/m2 [19 treatments]) following
      a standardized protocol. Goals other than PCWP and ITBVI were cardiac index of >
      3.5 L/min/m2 and mean arterial pressure of > 55 mm Hg. MEASUREMENTS AND RESULTS:
      In addition to the primary goals PCWP and ITBVI, at defined temperatures, central
      venous pressure (CVP), extravascular lung water index, the number of infusions,
      and packed RBCs, as well as serum lactate level, norepinephrine dosage, and
      levels of liver enzymes, bilirubin, creatinine, and urea were measured. Patients
      in group A received a significantly greater mean (+/- SD) amount of crystalloids
      compared to those in group B (6,175 +/- 656 vs 3,947 +/- 375 mL, respectively)
      and required significantly lower dosages of vasoconstrictors compared with
      patients in group B. Except for the lower values of CVP in patients in group A
      during hyperthermia, all of the other hemodynamic and laboratory parameters
      showed no significant differences between the groups or stayed in a normal range.
      CONCLUSION: PCWP and ITBVI are useful parameters to assess preload in induced
      WBH. Differences in crystalloids and vasopressor dosages may suggest an
      appropriate ITBVI of > 1,100 mL/m2 for patients with good cardiopulmonary health
      under such extremely hypercirculatory conditions.

PMID- 16100142
TI  - Short-term and long-term effects of nasal intermittent positive pressure
      ventilation in patients with obesity-hypoventilation syndrome.
AB  - OBJECTIVE: To assess the outcome of 54 patients with obesity-hypoventilation
      syndrome (OHS) who were treated with nasal intermittent positive-pressure
      ventilation (NIPPV). DESIGN: Descriptive analysis of retrospectively collected
      clinical data. MATERIALS AND METHODS: From March 1995 to December 2002, OHS
      (defined as a body mass index [BMI] of > 30 kg/m2, a daytime Pa(CO2) of > or = 50
      mm Hg, and a Pa(O2) of < 60 mm Hg in the absence of COPD) was diagnosed in 69
      cases. Fifteen patients (21.7%) refused to be treated with NIPPV, and 20 patients
      were started on NIPPV therapy electively and 34 following an acute exacerbation.
      We employed daytime arterial blood gas values and overnight pulse oximetry to
      determine the initial NIPPV modes and settings. The outcome measures were
      survival, clinical status, and arterial blood gas levels. RESULTS: Among the 54
      study patients (18 women), the mean (+/- SD) age was 56 +/- 13 years. The mean
      BMI was 44 +/- 8.8 kg/m2. Sleep apnea syndrome (apnea-hypopnea index, > 5) was
      present in 87% of the patients. At presentation, 22 of the 54 patients had
      experienced an acute hypercapnic respiratory failure (pH < 7.34). None of these
      patients required orotracheal intubation after NIPPV treatment. Initially, 2
      patients were treated with volume-preset ventilation, 49 patients used pressure
      preset equipment, and 3 patients employed continuous positive airway pressure
      (CPAP). Forty-seven patients required supplemental oxygen. At the end of the
      follow-up period (mean duration, 50 months), Pa(O2) had increased by 24 mm Hg
      from baseline (95% confidence interval [CI], 21 to 28 mm Hg; p < 0.0001) and
      Pa(CO2) had decreased by 17 mm Hg (95% CI, 13 to 20 mm Hg; p < 0.0001). NIPPV
      therapy improved subjective sleepiness (mean Epworth sleepiness scale score
      decrease, 16 +/- 5 to 6 +/- 2; p < 0.001), and dyspnea decreased in all but four
      patients. During follow-up, three patients died (one of them due to the
      progression of respiratory failure). NIPPV therapy could be withdrawn in 5
      patients who had achieved a sufficient weight loss, and the conditions of 16
      patients could be maintained without respiratory failure by the use of simple
      therapy with CPAP. CONCLUSIONS: NIPPV therapy is effective in the treatment of
      patients with OHS, providing a significant improvement in clinical status and gas
      exchange.

PMID- 16100143
TI  - Prolonged intubation rates after coronary artery bypass surgery and ICU risk
      stratification score.
AB  - OBJECTIVE: To determine prolonged intubation rates among patients undergoing
      coronary artery bypass graft (CABG) surgery, and to evaluate the ability of the
      Intensive Care Unit Risk Stratification Score (ICURSS) model to predict these
      events. DESIGN: Prospective observational study. SETTING: A 24-bed ICU in a
      tertiary referral university hospital. PATIENTS: Five hundred sixty-nine patients
      undergoing CABG surgery. INTERVENTIONS: Variables of the ICURSS model were
      recorded at ICU admission. Extubation was performed according to a standard
      protocol. Patients remaining intubated within 8 h after ICU admission were
      designated as having early extubation failure (EEF). The next evaluations at 16,
      24, 48, 72, and 96 h designated patients as having a prolonged intubation period
      (PIP) and prolonged mechanical ventilation (PMV) for 24, 48, 72, and 96 h. The
      ability of the ICURSS model to predict extubation failure at different cutoff
      values was measured using the Hosmer-Lemeshow goodness-of-fit test and the area
      under the receiver operating characteristic curve. MEASUREMENTS AND RESULTS:
      Prolonged intubation rates were as follows: EEF, 40.2%; PIP, 17.2%; PMV for 24 h,
      10.4%; PMV for 48 h, 7.6%; PMV for 72 h, 6.5%; and PMV for 96 h, 6.0%. At every
      cutoff, the ICURSS showed poor discrimination to predict the failure to be
      extubated. Calibration was also poor, although some ability to predict both EEF
      and PMV at > or = 48 h was shown. CONCLUSIONS: Prolonged intubation rates after
      undergoing CABG surgery in our setting were comparable with those of other
      reports from institutions where fast-track cardiac anesthesia is currently in
      practice. In our cohort, the ICURSS was not useful for the prediction of length
      of intubation.

PMID- 16100144
TI  - Short-acting beta-agonist prescription fills as a marker for asthma morbidity.
AB  - OBJECTIVES: Hospital admissions and emergency department (ED) visits have
      traditionally been used to assess the strength of association between
      environmental exposures, such as air pollution, and asthma morbidity. In the
      current study, we evaluate the use of short-acting beta-agonist (SABA)
      prescriptions as a surrogate marker for asthma exacerbation with respect to these
      more traditional markers. METHODS: Claims data for recipients covered by Illinois
      Medicaid with a diagnosis of asthma were obtained for fiscal-years 1996 through
      June 1998. Claims for short-acting bronchodilators and asthma-related ED visits
      and hospital admissions for 31,140 adults were identified. The odds ratio for the
      association of either an ED visit or hospital admission and an SABA prescription
      was calculated for time lags ranging from -28 to +28 days. Individual-subject
      heterogeneity and seasonal effects were corrected for using the Mantel-Haenszel
      method. RESULTS: After adjustment for individual and seasonal effects, there was
      a significant positive association between SABA prescriptions and ED visits or
      hospital admissions for asthma on any single day. In addition, a significant
      positive association was also found between the ED visits or hospital admissions
      occurring on the few days prior to an SABA prescription. No significant relation
      was found (after adjusting for subject and seasonal effects) between
      prescriptions and admissions when an SABA prescription date preceded that of a
      hospital admission or an ED visit. CONCLUSIONS: A very strong and significant
      association between ED visits or hospital admissions for asthma and SABA
      prescriptions was observed, which suggests that SABA prescription fills can be
      used as a marker for asthma morbidity. In addition, a temporal association exists
      between claims for ED visits or hospital admissions for asthma and SABA
      prescription claims when an ED visit or hospital admission precedes the SABA
      prescription.

PMID- 16100145
TI  - Relation of beta2-adrenoceptor polymorphisms at codons 16 and 27 to persistence
      of asthma symptoms after the onset of puberty.
AB  - BACKGROUND: It has long been recognized that many children with asthma outgrow
      the disease after the onset of puberty, but little is known about genetic factors
      influencing this outcome. OBJECTIVES: The aim of the present study was to
      determine whether the polymorphisms at codons 16 and 27 of the beta2-adrenoceptor
      are significant predictors of the persistence of asthma during adolescence.
      DESIGN AND PARTICIPANTS: We used data from the prospective Tucson Children's
      Respiratory Study. Children were genotyped for the polymorphisms at codons 16 and
      27. The presence of wheezing/asthma was assessed by questionnaire from age 6
      years up to the reported onset of puberty (prepubertal period) and after the
      onset of puberty up to age 16 years (adolescence). RESULTS: Among children who
      wheezed in the prepubertal period (n = 168), subjects homozygous for Gly at codon
      16 were at significantly increased risk for persistent wheezing after puberty, as
      compared with carriers of the other genotypes (relative risk [RR], 1.43; 95%
      confidence interval [CI], 1.06 to 1.92; p = 0.019). This relation was present
      among boys (RR, 2.17; 95% CI, 1.41 to 3.36) but not girls (RR, 0.85; 95% CI, 0.55
      to 1.30), and increased linearly according to the frequency of wheezing episodes
      after the onset of puberty. These findings persisted after adjusting for
      ethnicity and other potential confounders and after selecting only white
      children. The polymorphism at codon 27 showed no relation with risk for
      persistent wheezing. CONCLUSIONS: This study provides evidence for a strong
      gender-specific effect of the Gly16 polymorphism on the persistence of asthma
      after the onset of puberty.

PMID- 16100146
TI  - Obstructive sleep apnea syndrome in morbid obesity: effects of intragastric
      balloon.
AB  - STUDY OBJECTIVES: In obese patients, obstructive sleep apnea syndrome (OSAS) is
      attributed to a reduction in pharyngeal cross-sectional area due to
      peripharyngeal fat deposition. The effect of weight loss on the size of the upper
      airways of obese subjects is still unknown. We analyzed the pharyngeal cross
      sectional area before and after weight loss in morbidly obese patients with OSAS.
      DESIGN, SETTING, AND SUBJECTS: A group of 17 middle-aged, morbidly obese men was
      evaluated by anthropometry and cardiorespiratory sleep studies before and after
      weight loss obtained by insertion of an intragastric balloon. The pharyngeal
      cross-sectional area was measured by acoustic pharyngometry. RESULTS: The mean
      (+/- SD) body mass index was 55.8 +/- 9.9 kg/m2 at baseline and 48.6 +/- 11.2
      kg/m2 at the time of balloon removal (6 months after insertion) [p < 0.001]. At
      baseline, patients had visceral obesity, large necks, and severe OSAS. Weight
      loss was associated with a significant mean reduction of waist circumference
      (156.4 +/- 17.6 vs 136.7 +/- 18.4 cm, respectively; p < 0.001), sagittal
      abdominal diameter (37.8 +/- 3.0 vs 32.3 +/- 4.0 cm, respectively; p < 0.001),
      and neck circumference (51.1 +/- 3.7 vs 47.9 +/- 4.3 cm, respectively; p <
      0.001). Moreover, weight loss induced a nearly complete resolution of OSAS (apnea
      hypopnea index, 52.1 +/- 14.9 vs 14.0 +/- 12.4 events/h, respectively; p <
      0.001). At baseline, obese patients had significantly lower pharyngeal cross
      sectional areas compared to a group of 20 nonobese male control subjects, both in
      the upright and supine position, at different levels of the pharynx. In obese
      patients, the weight loss induced by the positioning of the intragastric balloon
      was associated with an increase in the size of the upper airway passage. After
      weight loss, both the mean pharyngeal cross-sectional area and the area at
      glottis level were still lower in obese subjects than in nonobese subjects;
      however, the pharyngeal cross-sectional area at the oropharyngeal junction was
      similar in the two groups. CONCLUSIONS: Morbidly obese men with OSAS have a
      reduced pharyngeal cross-sectional area. A weight reduction of about 15% of
      baseline body weight may substantially increase the pharyngeal cross-sectional
      area and substantially improve the severity of OSAS in morbidly obese subjects
      with sleep apnea.

PMID- 16100147
TI  - Mortality in obstructive sleep apnea-hypopnea patients treated with positive
      airway pressure.
AB  - STUDY OBJECTIVES: The aims of this study were to analyze mortality in patients
      with obstructive sleep apnea-hypopnea syndrome (OSAHS) treated with positive
      airway pressure (PAP) and to know whether PAP compliance affects survival, as
      well as to investigate the prognostic value of several pretreatment variables.
      DESIGN AND PATIENTS: A study was made of an historical cohort of 871 patients in
      whom OSAHS had been diagnosed by sleep study between January 1994 and December
      2000 and who had been treated with PAP. Patients were followed up until December
      2001. The mean (+/- SD) age of the group was 55.4 +/- 10.6 years, the mean apnea
      hypopnea index (AHI) 55.1 +/- 28.7, and 80.9% were men. To assess whether
      mortality was influenced by PAP therapy compliance, patients were assigned to one
      of the following compliance categories: < 1 h/d; 1 to 6 h/d; or > 6 h/d. Survival
      rates were calculated according to the Kaplan-Meier method. Survival curves were
      compared with the log-rank test and the trend test, when necessary. Univariate
      and multivariate analyses using a time-dependent Cox model were performed to
      elicit which variables correlated with mortality. SETTING: Outpatient sleep
      disorders unit. RESULTS: By the end of the follow-up period (mean duration, 48.5
      +/- 22.7 months), 46 patients had died. The 5-year cumulative survival rates were
      significantly lower in patients who did not use PAP (compliance < 1 h) than in
      those who used the device for > 6 h/d (85.5% [95% confidence interval (CI), 0.78
      to 0.92] vs 96.4% [95% CI, 0.94 to 0.98; p < 0.00005]) and 1 to 6 h/d (85.5% [95%
      CI, 0.78 to 0.92] vs 91.3% [ 95% CI, 0.88 to 0.94; p = 0.01]), respectively. A
      trend in survival rates across the groups was identified (p = 0.0004). The main
      cause of death in 19 cases was cardiovascular disease (CVD). Variables that
      independently correlated with mortality in the multivariate analysis were the
      following PAP use categories: compliance for > 6 h/d (odds ratio [OR], 0.10; 95%
      CI, 0.04 to 0.29); compliance for 1 to 6 h/d (OR, 0.28; 95% CI, 0.11 to 0.69);
      arterial hypertension (AHT) [OR, 3.25; 95% CI, 1.24 to 8.54]; age (OR, 1.06; 95%
      CI, 1.01 to 1.10); and FEV1 percent predicted (OR, 0.96; 95% CI, 0.94 to 0.98).
      CONCLUSION: Mortality rates in OSAHS patients who did not receive PAP therapy
      were higher compared with those treated with PAP and were moderately or highly
      compliant with therapy. A trend in survival across compliance categories was
      found. Patients died mainly from CVD. Categories of PAP compliance, AHT, age, and
      FEV1 percent predicted were the variables that independently predicted mortality.

PMID- 16100148
TI  - The local component of the acute cardiovascular response to simulated apneas in
      brain-dead humans.
AB  - STUDY OBJECTIVES: To investigate the local cardiovascular response to hypoxemia
      and hypercapnia in a simulated central apnea model in which the central autonomic
      regulation was absent. DESIGN: Experimental study. SETTING: A university
      hospital. INTERVENTIONS: A simulated central apnea model achieved by a particular
      setting of the mechanical ventilator in 10 brain-dead patients. MEASUREMENTS:
      Hemodynamic studies using right-heart catheterization and continuous monitoring
      of arterial blood gas levels. RESULTS: Hypercapnic hypoxic apneas were associated
      with no change in heart rate, fall in mean systemic arterial pressure and
      systemic vascular resistance (from 83 +/- 9 to 68 +/- 7 mm Hg and 1,115 +/- 82 to
      768 +/- 58 dyne.s.cm(-5), respectively; each p < 0.05), and rise in mean
      pulmonary artery pressure, pulmonary vascular resistance, and pulmonary capillary
      wedge pressure (PCWP) [from 17 +/- 1.5 to 26 +/- 3 mm Hg, 102 +/- 27 to 166 +/-
      43 dyne.s.cm(-5), and 10 +/- 1 to 14 +/- 2 mm Hg, respectively; each p < 0.05].
      CONCLUSION: Our results suggest that in the absence of central autonomic
      regulation in humans, apnea-induced hypoxemia and/or hypercapnia are associated
      with peripheral vasodilatation and pulmonary vasoconstriction, which are probably
      local in origin, as well as a significant increase in PCWP indicating cardiac
      dysfunction.

PMID- 16100149
TI  - Effects of imposed pursed-lips breathing on respiratory mechanics and dyspnea at
      rest and during exercise in COPD.
AB  - STUDY OBJECTIVES: To investigate the effect of volitional pursed-lips breathing
      (PLB) on breathing pattern, respiratory mechanics, operational lung volumes, and
      dyspnea in patients with COPD. SUBJECTS: Eight COPD patients (6 male and 2
      female) with a mean (+/-SD) age of 58 +/- 11 years and a mean FEV1 of 1.34 +/-
      0.44 L (50 +/- 21% predicted). METHODS: Wearing a tight-fitting transparent
      facemask, patients breathed for 8 min each, with and without PLB at rest and
      during constant-work-rate bicycle exercise (60% of maximum). RESULTS: PLB
      promoted a slower and deeper breathing pattern both at rest and during exercise.
      Whereas patients had no dyspnea with or without PLB at rest, during exercise
      dyspnea was variably affected by PLB across patients. Changes in the individual
      dyspnea scores with PLB during exercise were significantly correlated with
      changes in the end-expiratory lung volume (EELV) values estimated from
      inspiratory capacity maneuvers (as a percentage of total lung capacity; r2 =
      0.82, p = 0.002) and with changes in the mean inspiratory ratio of pleural
      pressure to the maximal static inspiratory pressure-generating capacity (PcapI)
      [r2 = 0.84; p = 0.001], measured using an esophageal balloon, where PcapI was
      determined over the range of inspiratory lung volumes and adjusted for flow.
      CONCLUSION: PLB can have a variable effect on dyspnea when performed volitionally
      during exercise by patients with COPD. The effect of PLB on dyspnea is related to
      the combined change that it promotes in the tidal volume and EELV and their
      impact on the available capacity of the respiratory muscles to meet the demands
      placed on them in terms of pressure generation.

PMID- 16100150
TI  - Dyspnea, ventilatory pattern, and changes in dynamic hyperinflation related to
      the intensity of constant work rate exercise in COPD.
AB  - STUDY OBJECTIVE: We undertook the present study to investigate the perception of
      dyspnea (with respect to changes in end-inspiratory and end-expiratory lung
      volumes), during four different levels of high-intensity constant work rate
      exercise (CWRE) in patients with severe COPD. DESIGN: Crossover descriptive study
      with consecutively recruited subjects. SETTING: Tertiary university hospital.
      PATIENTS: Twenty-seven subjects with severe COPD (mean [+/- SD] age, 65 +/- 5
      years of age; mean FEV1, 43 +/- 8% predicted; and mean inspiratory capacity [IC];
      74 +/- 14% predicted). MEASUREMENTS AND RESULTS: Subjects randomly performed four
      high-intensity CWRE tests (conducted at 65%, 75%, 85%, and 95% of their symptom
      limited peak work rate). Dyspnea, leg fatigue, and IC were determined every 2 min
      during exercise with breath-by-breath gas exchange and ventilatory measurements.
      There was a good correlation between the resting IC percent predicted and the
      oxygen uptake (V(O2)) peak (r = 0.64 to 0.69 between the IC percent predicted and
      V(O2) peak at the four work rates). There were significant differences (p < 0.01)
      in mean respiratory rate (33 +/- 6, 35 +/- 6, 37 +/- 6, and 38 +/- 6 min), peak
      dyspnea score (5.9 +/- 1.3, 6.3 +/- 1.4, 6.8 +/- 1.2, and 6.9 +/- 1.6), minute
      ventilation (45.0 +/- 8.7, 43.8 +/- 7.7, 43.1 +/- 8.7, and 42.8 +/- 8.0 L/min),
      leg fatigue (4.8 +/- 1.3, 5.1 +/- 1.3, 5.7 +/- 1.4, and 5.8 +/- 1.4), and end
      tidal carbon dioxide partial pressure (4.41 +/- 0.36, 4.53 +/- 0.33, 4.66 +/-
      0.31, and 4.76 +/- 0.24 kPa), respectively, for tests conducted at 65%, 75%, 85%,
      and 95% of their symptom-limited peak work rate, and in mean end-expiratory lung
      volume ([EELV] 4.55 +/- 0.44, 4.69 +/- 0.43, and 4.79 +/- 0.43 L), respectively,
      for tests conducted at 65%, 75%, and 85% of their symptom-limited peak work rate.
      In multivariable analysis, the factors that were independently correlated with
      dyspnea (p < 0.05) were EELV, peak inspiratory flow, and leg fatigue/discomfort.
      CONCLUSION: In COPD subjects with flow limitation at rest, the perception of
      dyspnea increased nonlinearly with the magnitude of high-intensity CWRE in
      association with a faster respiratory pattern and an increase in EELV. At the
      highest work rates, it appeared that a reduction in tidal volume and ventilation
      peak may have limited the tolerance to exercise.

PMID- 16100151
TI  - Outcome of patients with stable COPD receiving controlled noninvasive positive
      pressure ventilation aimed at a maximal reduction of Pa(CO2).
AB  - STUDY OBJECTIVES: The role of noninvasive positive pressure ventilation (NPPV)
      has been well established in the treatment of acute hypercapnic respiratory
      failure due to COPD. However, evidence for a sustained improvement in blood gas
      levels and survival in patients with stable hypercapnic COPD following NPPV is
      still lacking. There is concern that this might be due to low inspiratory
      pressures of < 18 cm H2O used in previous studies, which thereby did not achieve
      a reduction of Pa(CO2). Therefore, the 2-year survival and changes in lung
      function and blood gas levels were analyzed in patients with stable hypercapnic
      COPD in whom controlled pressure-limited NPPV was titrated to achieve a maximal
      improvement in Pa(CO2). DESIGN: Retrospective study between March 1997 and
      September 2003. SETTING: General ward of a university hospital. PATIENTS: Thirty
      four consecutive patients with stable (mean pH 7.40 +/- 0.03) hypercapnic COPD
      (mean age, 63.4 +/- 9.7 years [+/- SD]; mean body mass index, 28.3 +/- 7.3
      kg/m2). MEASUREMENTS AND RESULTS: Daytime Pa(CO2) during spontaneous breathing
      decreased by 6.9 +/- 8.0 (95% confidence interval, - 9.9 to - 3.9), from 53.3 +/-
      4.8 to 46.4 +/- 7.0 mm Hg (p < 0.001); while daytime Pa(O2) increased by 5.8 +/-
      9.4 (95% confidence interval, 2.3 to 9.3), from 51.7 +/- 8.8 to 57.5 +/- 9.3 mm
      Hg (p = 0.002); and FEV1 increased by 0.14 +/- 0.16 (95% confidence interval,
      0.08 to 0.20), from 1.03 +/- 0.54 to 1.17 +/- 0.59 L (p < 0.001) after 2 months
      of NPPV. This was achieved with mean inspiratory pressures of 27.7 +/- 5.9 cm H2O
      (range, 17 to 40 cm H2O) at a mean respiratory rate of 20.8 +/- 2.5 breaths/min
      (range, 14 to 24 breaths/min). The 2-year survival rate was 86%. CONCLUSIONS:
      Controlled NPPV using a mean inspiratory pressure of 28 cm H2O is well tolerated
      over longer periods and can improve blood gas levels and lung function.
      Prospective, randomized controlled trials of high-intensity NPPV are required to
      evaluate its role in patients with stable hypercapnic COPD.

PMID- 16100152
TI  - The effectiveness of different combinations of pulmonary rehabilitation program
      components: a randomized controlled trial.
AB  - STUDY OBJECTIVES: To study the short-term and long-term effects of combining
      activity training or lectures to exercise training on quality of life, functional
      status, and exercise tolerance. DESIGN: Randomized clinical trial. SETTING:
      Outpatient pulmonary rehabilitation center. PARTICIPANTS: Forty-three outpatients
      with COPD. INTERVENTIONS: Patients were randomized to one of three treatment
      groups: exercise training alone, exercise training plus activity training, and
      exercise training plus a lecture series. The mean treatment period was 10 weeks.
      MEASUREMENT: The Chronic Respiratory Disease Questionnaire, the modified version
      of the Pulmonary Functional Status and Dyspnea Questionnaire, and the COPD Self
      Efficacy Scale were administered at baseline, and 6, 12, 18, and 24 weeks from
      the beginning of the rehabilitation program. The 6-min walk test was used to
      measure exercise tolerance. RESULTS: Benefits of activity training combined with
      exercise included less dyspnea (p < or = 0.04) and fatigue (p < or = 0.01), and
      increased activity involvement (p < or = 0.02) and total functional status (p <
      or = 0.02) in the short term compared to comparison treatment groups for
      comparatively older participants. Compared to the lecture series adjunct, the
      activity training adjunct resulted in significantly higher gains in total quality
      of life (p = 0.04) maintained at 24 weeks. Significantly worse emotional function
      and functional status resulted from the lecture series adjunct in the oldest
      participants (p < or = 0.03). Treatment groups did not differ significantly on
      exercise tolerance or self-efficacy. CONCLUSIONS: Evidence for additional
      benefits of activity-specific training combined with exercise was found. A
      behavioral method emphasizing structured controlled breathing and supervised
      physical activity was statistically significantly more effective than didactic
      instruction in facilitating additional gains and meeting participants' learning
      needs.

PMID- 16100153
TI  - The effects of short-term and long-term pulmonary rehabilitation on functional
      capacity, perceived dyspnea, and quality of life.
AB  - STUDY OBJECTIVES: The purposes of this study were as follows: (1) to determine
      whether physical performance, quality of life, and dyspnea with activities of
      daily living improved following both short-term and long-term pulmonary
      rehabilitation (PR) across multiple hospital outpatient programs; (2) to examine
      the differences in these parameters between men and women; and (3) to determine
      what relationships existed between the psychosocial parameters and the results of
      the 6-min walk (6MW) test performance across programs. DESIGN: Non-experimental,
      prospective, and comparative. SETTING: Seven outpatient hospital PR programs from
      urban and rural settings across North Carolina. PARTICIPANTS: Three hundred nine
      women and 281 men who were 20 to 93 years of age (mean [+/- SD] age, 66.7 +/-
      11.1 years) with chronic lung disease. INTERVENTIONS: All 6MW tests and health
      surveys were administered prior to and immediately following 12 and 24 weeks of
      supervised PR participation. Scores from the 6MW tests, the Ferrans and Powers
      quality of life index-pulmonary version III (QLI), the Medical Outcomes Study 36
      item short form (SF-36), and the University of California at San Diego shortness
      of breath questionnaire (SOBQ) were compared at PR entry, at 12 weeks, and at 24
      weeks for differences by gender with repeated-measures analysis of variance. The
      study entry and follow-up SF-36 physical and mental component summary scores, the
      QLI health/function and overall scores, and the SOBQ scores were also compared to
      the 6MW test scores with Pearson correlation coefficient analysis. RESULTS: The
      mean summary scores on the SF-36 and the QLI increased after 12 weeks of PR (p <
      0.05), and improvements were maintained by 24 weeks of PR participation (p <
      0.05). Scores on the SOBQ improved after 12 weeks (p < 0.001) among the short
      term participants, but not until after 24 weeks among the long-term participants
      (p = 0.009). The 6MW test performance improved after 12 weeks (p < 0.001) and
      again from 12 to 24 weeks (p = 0.002) in the long-term participants. No relevant
      correlational relationships were found between 6MW scores and the summary scores
      of the administered surveys (r = -0.43 to 0.36). CONCLUSIONS: Physical
      performance, as measured by the 6MW test, continued to improve with up to 24
      weeks of PR participation. Quality-of-life measures and the perception of dyspnea
      improved after 12 weeks of PR participation, with improvements maintained by 24
      weeks of PR participation. It is recommended that PR patients participate in
      supervised PR for at least 24 weeks to gain and maintain optimal health benefits.

PMID- 16100154
TI  - Prospective randomized trial of silver nitrate vs talc slurry in pleurodesis for
      symptomatic malignant pleural effusions.
AB  - STUDY OBJECTIVES: To compare the efficacy and the safety of talc slurry and
      silver nitrate (SN) in the treatment of symptomatic malignant pleural effusions.
      PATIENTS AND METHODS: Sixty patients were enrolled into the study, and all
      received a chest tube (26F or 28F) that was placed using local anesthesia. The
      patients were randomized to receive either 5 g talc diluted to a total volume of
      50 mL with saline solution or 20 mL 0.5% SN through the chest tube. Patients were
      clinically evaluated before and after treatment regarding pain, and were
      evaluated at monthly intervals with respect to the effectiveness of pleurodesis.
      Eleven patients did not return for their 30-day follow-up visit and were excluded
      from further analysis. Pleurodesis therapy was considered to be successful if
      there was no recurrence of the effusion. The patients who did not have a
      pleurodesis at one visit were excluded from subsequent visits. RESULTS: Forty
      nine patients returned at 30 days for follow-up, including 24 patients who
      received SN and 25 who received talc. The groups were similar in age (p = 0.23),
      sex (p = 0.70), Karnofsky index (p = 0.94), and pathology (p = 0.68). After the
      induction of pleurodesis, neither the total mean (+/- SE) fluid drainage (SN, 901
      +/- 125 mL; talc, 766 +/- 74 mL; p = 0.36) nor the level of pain (SN, 2.58 +/-
      0.26; talc, 2.62 +/- 0.30; p = 0.91) differed significantly between the groups,
      and no patient in either group developed ARDS. The mean number of days spent in
      the hospital was nearly identical (SN group, 3.7 +/- 0.15 days; talc group, 3.6
      +/- 0.13 days; p = 0.47). Both SN and talc were effective agents. Thirty days
      after the procedure, 23 of 24 patients (96%) who had received SN and 21 of 25
      patients (84%) who had received talc showed an effective pleurodesis (p = 0.35).
      Similar results were observed after 60 days (SN group, 18 of 18 patients [100%];
      talc group, 13 of 13 patients [100%]; p = > 0.99), 90 days (SN group, 16 of 16
      patients [100%]; talc, 8 of 9 patients [89%]; p = 0.36), and 120 days (SN group,
      4 of 4 patients [100%]; talc group, 4 of 4 patients [100%]; p > 0.99).
      CONCLUSIONS: The present study suggests that SN is an effective agent for
      producing a pleurodesis. In the present study, SN showed a tendency to be more
      effective than talc, but the power of the test to detect a significance
      difference was low in this small group of patients. The side effects of 0.5% SN
      appear to be minimal, but since only a small number of patients received SN and
      nearly 20% of the patients were lost to follow-up, significant long-term side
      effects cannot be excluded. Since SN appears to be as effective as talc, and
      since there is no evidence that it induces ARDS as has been reported with talc,
      it should be considered as an alternative to talc for the production of a
      pleurodesis.

PMID- 16100155
TI  - Proinflammatory cytokines, transforming growth factor-beta1, and fibrinolytic
      enzymes in loculated and free-flowing pleural exudates.
AB  - STUDY OBJECTIVES: To measure tumor necrosis factor (TNF) alpha, interleukin (IL)
      1beta, and transforming growth factor (TGF) beta1 in loculated and free-flowing
      pleural effusions caused by malignancy, tuberculosis (TB), and pneumonia and
      their relationship with plasminogen activator inhibitor-type 1 (PAI-1) and tissue
      type plasminogen activator (tPA) and to compare the differences between loculated
      and free-flowing effusions. DESIGN: A prospective study. PATIENTS AND METHODS:
      The effusion levels of TNF-alpha, IL-1beta, TGF-beta1, PAI-1, and tPA were
      measured in 29 patients with malignant effusions, 19 patients with TB, and 30
      patients with parapneumonic effusions. Pleural effusions were divided into
      loculated and free-flowing groups by imaging studies. A group of 42 patients with
      loculated effusions was subdivided into primary and secondary loculation groups
      by chest ultrasonography. RESULTS: The median levels of TNF-alpha (87.0 pg/mL),
      IL-1beta (13.8 pg/mL), TGF-beta1 (10,952.9 pg/mL), PAI-1 (111.2 ng/mL), and
      lactate dehydrogenase (LDH) [498 IU/dL] in the loculated group were significantly
      higher than those in the free-flowing group (TNF-alpha, 15.0 pg/mL; IL-1beta, 2.9
      pg/mL; TGF-beta1, 6,117.3 pg/mL; PAI-1, 61.5 ng/mL, and LDH, 266 IU/dL). In both
      the loculated and free-flowing effusions, the levels of TGF-beta1 correlated
      positively with those of TNF-alpha (r = 0.51 and p < 0.001 vs r = 0.42 and p <
      0.05, respectively) and IL-1beta (r = 0.52 and p < 0.001 vs r = 0.49 and p <
      0.01, respectively), and the values of PAI-1 correlated positively with those of
      TNF-alpha (r = 0.59 and p < 0.001 vs r = 0.55 and p < 0.001, respectively), IL
      1beta (r = 0.35 and p < 0.05 vs r = 0.47 and p < 0.01, respectively), and TGF
      beta1 (r = 0.53 and p < 0.001 vs r = 0.58 and p < 0.001, respectively). In
      contrast, the levels of tPA correlated negatively with those of TNF-alpha (r = 
      0.37, p < 0.05) and IL-1beta (r =-0.56, p < 0.001) in loculated effusions. Twenty
      seven of 42 patients with loculated effusions were classified into a secondary
      loculation group, which, compared with the primary loculation group, had
      significantly higher median levels of effusion TNF-alpha (119.2 vs 14.2 pg/mL,
      respectively; p = 0.001), IL-1beta (33.3 vs 3.4 pg/mL, respectively; p < 0.001),
      TGF-beta1 (13,152.7 vs 7746.0 pg/mL, respectively; p = 0.041), and PAI-1 (114.9
      vs 94.1 pg/mL, respectively; p = 0.019). CONCLUSION: Compared with free-flowing
      effusions, fibrinolytic activity was depressed in loculated effusions. A higher
      intensity of pleural inflammation in loculated effusions may enhance the release
      of TNF-alpha, IL-1beta, and TGF-beta1, which may subsequently increase the levels
      of PAI-1. The imbalance of PAI-1 and tPA in pleural spaces may lead to fibrin
      deposition and loculation of pleural effusions.

PMID- 16100156
TI  - The impact of positron emission tomography on clinical decision making in a
      university-based multidisciplinary lung cancer practice.
AB  - INTRODUCTION: Positron emission tomography (PET) scanning has gained increasing
      application as a diagnostic and staging tool in the evaluation of lung cancer.
      Although PET scanning has been demonstrated to be a cost-effective adjunct to
      lung cancer diagnosis, its global impact on clinical decision making has not been
      assessed. STUDY OBJECTIVES: To evaluate the impact of the systematic use of PET
      scanning on clinical decision making. DESIGN: Retrospective study. SETTING: A
      university-based multidisciplinary lung cancer practice. PATIENTS: All patients
      undergoing diagnostic or staging PET scans from December 31, 2000, to December
      31, 2002. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: One hundred ninety-eight
      patients underwent PET for diagnosis (161 patients) or staging (37 patients). PET
      scan results and clinical outcomes were retrospectively reviewed to determine the
      frequency with which PET scan findings (1) upstaged patients, (2) downstaged
      patients, (3) changed the diagnostic workup, (4) altered therapy, (5) resulted in
      a significant additional diagnosis, and (6) triggered evaluations that ultimately
      proved fruitless. PET upstaged 32 of 198 patients (16.2%) and downstaged 12
      patients (6.1%), facilitating curative resection in 4 patients. Overall, PET scan
      findings changed the stage in 44 patients (22.2%). PET scan findings changed
      diagnostic management in 105 of 198 patients (53%), among whom biopsy was
      deferred in 65 patients (61.9%) and was triggered or guided in 40 patients
      (38.1%). PET scan findings altered treatment decisions in 38 patients (19.2%),
      leading to neoadjuvant therapy in 6 patients and resection in 5 patients, and
      forestalling noncurative thoracotomy in 6 patients. PET scan findings prompted or
      redirected chemotherapy or radiotherapy in the remainder of the patients.
      Overall, PET scan findings changed management in 143 patients (72.2%). PET scan
      findings triggered additional diagnostic testing in 32 patients (16.2%),
      resulting in no new diagnosis in 16 patients (50%) and a critical change in
      management in 7 patients (21.9%). PET scan findings were solely responsible for a
      significant non-lung cancer diagnosis in eight patients (4%). CONCLUSIONS:
      Systematically applied PET scanning has a significant impact on patient
      management, altering diagnostic or therapeutic interventions in 72.2% of
      patients, changing staging in 22.2% of patients, and identifying serious
      unsuspected diagnoses in 4.0% of patients, with potentially life-saving
      consequences in 2.0%. Key Words: diagnosis; lung neoplasms; positron emission
      tomography.

PMID- 16100157
TI  - Transbronchial needle aspiration in the diagnosis of endobronchial malignant
      lesions: a 3-year experience.
AB  - STUDY OBJECTIVES: To establish the diagnostic yield of transbronchial needle
      aspiration (TBNA) and its contribution to conventional diagnostic techniques
      (CDT) such as forceps biopsy, bronchial washing, and bronchial brushing in the
      diagnosis of malignant endobronchial lesions. DESIGN: Retrospective clinical
      study. PATIENTS: One hundred fifteen lung cancer patients MEASUREMENT AND
      RESULTS: We reviewed files of 115 lung carcinoma cases diagnosed in our clinic
      from 2001 to 2003 with endobronchial lesions sampled by CDT and TBNA. The lesions
      were classified into three groups: exophitic mass lesion (EML), submucosal
      disease, and peribronchial disease. The diagnostic yield of TBNA and CDT was
      compared to that of the combination of CDT and TBNA with respect to the type and
      location of the lesion and the histopathologic subgroups. Of the 115 cases,
      histology findings were confirmed by TBNA in 91 cases (79%), CDT in 75 cases
      (65%), and TBNA plus CDT in 105 cases (91%). The difference of the diagnostic
      yield of CDT vs TBNA plus CDT was statistically significant (p < 0.001). In
      peribronchial disease, the sensitivity of TBNA plus CDT was significantly better
      than CDT (87% vs 52%, p < 0.001). In EML and submucosal disease, addition of TBNA
      to CDT improved sensitivity from 85 to 100% and from 84 to 97%, respectively (p >
      0.05). Regarding localization, the addition of TBNA to CDT increased sensitivity
      in the trachea and main bronchi, and in right upper and middle lobe lesions (p <
      0.05). By the addition of TBNA to CDT, small cell lung cancer and non-small cell
      lung cancer cases demonstrated improvements in sensitivity from 74 to 100% and 61
      to 87%, respectively. This significant difference (p < 0.05) was attributed to
      the peribronchial disease group. CONCLUSION: In the case of peribronchial
      disease, the addition of TBNA to CDT improves the diagnostic yield of the
      bronchoscopic examination.

PMID- 16100158
TI  - Bosentan improves exercise tolerance and Tei index in patients with pulmonary
      hypertension and prostanoid therapy.
AB  - STUDY OBJECTIVE: Pulmonary arterial hypertension (PAH) is a progressive disease
      with a bad prognosis. Prostanoids are well established in the medical treatment
      of this disease. Treatment of patients with progressive disease despite
      prostanoids remains a therapeutic challenge. In this study, we examined the
      effect of adding bosentan, an endothelin antagonist, to existing prostanoid
      therapy on exercise capacity (6-min walking distance [6MWD]) and right
      ventricular (RV) function (Tei index) in patients with progressive pulmonary
      hypertension. DESIGN: Prospective, nonrandomized, open-label study. SETTING:
      University hospital. PATIENTS: Sixteen patients with pulmonary hypertension (PAH,
      n = 10; pulmonary hypertension due to other cause, n = 6) with progressive
      disease receiving either beraprost (n = 3), inhaled iloprost (n = 10), or
      iloprost IV (n = 3). INTERVENTIONS: Combination therapy with bosentan (final
      dosage, 125 mg bid) was initiated following an interval of 3-months minimum of
      unchanged prostanoid therapy. MEASUREMENTS AND RESULTS: Tei index, 6MWD, and New
      York Heart Association (NYHA) functional class were assessed prior to the
      initiation of combination therapy (baseline), at 6 months after initiation of
      combination therapy, and every 3 months thereafter. Two patients were followed up
      for 6 months only; all remaining patients reached a mean follow-up period (+/-
      SD) of 13.5 +/- 5.0 months (range, 9 to 22 months). 6MWD increased by 42.5 +/- 66
      m at 6 months and 44.6 +/- 66 m at the last follow-up (both time points vs
      baseline, p < 0.001), and Tei index improved by -0.13 +/- 0.08 at 6 months and -
      0.13 +/- 0.11 at the last follow-up (both time points vs baseline, p < 0.001).
      All patients reported subjective improvements. Nine of 16 patients exhibited
      improvement in NYHA functional class at 6 months. No side effects occurred that
      required dose adjustment or discontinuation of the study medication. CONCLUSION:
      Bosentan administered to patients with progressive pulmonary hypertension
      receiving prostanoids resulted in an increased exercise capacity and an improved
      RV function. Bosentan therefore appears to be well suited for combination therapy
      with prostanoids in selected patients pending results of ongoing randomized
      trials.

PMID- 16100159
TI  - Effects of lipo-prostaglandin E1 on pulmonary hemodynamics and clinical outcomes
      in patients with pulmonary arterial hypertension.
AB  - OBJECTIVE: To determine whether lipid microspheres containing prostaglandin E1
      (lipo-PGE1) improve pulmonary hemodynamics and clinical outcomes in patients with
      pulmonary arterial hypertension (PAH). METHODS: Forty-nine patients with PAH (8
      patients with primary pulmonary hypertension, 21 patients with collagen vascular
      disease, 20 patients with congenital systemic-to-pulmonary shunts) were randomly
      classified into a conventional therapy group (n = 22) or a group receiving lipo
      PGE1 plus conventional drugs (lipo-PGE1 group; n = 27). Echocardiographic
      pulmonary parameters, New York Heart Association (NYHA) functional class, and
      Bruce treadmill test results for exercise capacity were recorded before and after
      treatment. RESULTS: After 2 weeks of treatment with lipo-PGE1 (10 microg bid for
      14 days), there were significant improvements in the values (+/- SD) for systolic
      pulmonary arterial pressure (SPAP) [76.9 +/- 27.9 mm Hg vs 66.5 +/- 22.8 mm Hg, p
      < 0.001]; total pulmonary resistance (27.2 +/- 13.3 dyne.s.cm(-5) vs 20.2 +/-
      10.7 dyne.s.cm(-5), p < 0.001); left ventricular ejection fraction (58.7 +/- 9.6%
      vs 64.4 +/- 6.8%, p < 0.001); and cardiac output (3.1 +/- 0.8 L/min vs 3.7 +/-
      1.1 L/min, p < 0.01). The NYHA functional class decreased from 3.0 +/- 0.6 to 2.5
      +/- 0.6 (p < 0.001), and the exercise capacity increased from 2.8 +/- 1.0 to 4.3
      +/- 1.3 metabolic equivalents (MET) [p < 0.001]. Compared with the conventional
      therapy group, the lipo-PGE(1) group achieved significant reduction of SPAP (10.4
      +/- 10.3 mm Hg vs 2.2 +/- 5.6 mm Hg, p = 0.002) and a significant elevation of
      exercise capacity (1.5 +/- 0.9 MET vs 0.6 +/- 1.1 MET, p = 0.018). CONCLUSION:
      Lipo-PGE1 can decrease pulmonary artery pressure and increase exercise capacity
      in patients with PAH.

PMID- 16100160
TI  - Pneumothorax in cystic fibrosis.
AB  - BACKGROUND: Spontaneous pneumothorax is a complication that is commonly reported
      in patients with cystic fibrosis (CF). An understanding of the pathophysiology of
      this complication and its consequences is important for the management of
      patients with CF. OBJECTIVE: To identify risk factors associated with
      pneumothorax and to determine the prognosis of CF patients following an episode
      of pneumothorax. DESIGN: A retrospective observational cohort study of the
      National Cystic Fibrosis Patient Registry between the years 1990 and 1999.
      PATIENTS: The registry contained data on 28,858 patients with CF who had been
      followed up over those 10 years at CF centers across the United States. RESULTS:
      Pneumothorax occurred with an average annual incidence of 0.64% and in 3.4% of
      patients overall. There was no increased occurrence by sex, but CF was more
      prevalent in older patients (mean [+/- SD] age, 21.9 +/- 9.1 years) with more
      severe pulmonary impairment (nearly 75% of patients with FEV1 of < 40%
      predicted). The principal risks associated with an increased occurrence of
      pneumothorax included the presence of Pseudomonas aeruginosa (odds ratio [OR],
      2.3), Burkholderia cepacia (OR, 1.8), or Aspergillus (OR, 1.3) in sputum
      cultures, FEV1 < 30% predicted (OR, 1.5), enteral feeding (OR, 1.7), Medicaid
      insurance (OR, 1.1), pancreatic insufficiency (OR, 1.4), allergic
      bronchopulmonary aspergillosis (OR, 1.5), and massive hemoptysis (OR, 1.4). There
      is an increased morbidity (eg, increased number of hospitalizations and number of
      days spent in the hospital) and an increased 2-year mortality rate following
      pneumothorax. CONCLUSION: Pneumothorax is a serious complication in CF patients,
      occurring more commonly in older patients with more advanced lung disease. Nearly
      1 in 167 patients will experience this complication each year. There is an
      attributable mortality to the complication and considerable morbidity, resulting
      in increased health-care utilization and a measurable decline in lung function.

PMID- 16100161
TI  - Massive hemoptysis in cystic fibrosis.
AB  - BACKGROUND: Massive hemoptysis is a complication commonly reported in patients
      with cystic fibrosis (CF). An understanding of the pathophysiology of this
      complication and its consequences is important for the management of patients
      with CF. OBJECTIVES: To identify risk factors associated with massive hemoptysis,
      and to determine the prognosis of patients following an episode of massive
      hemoptysis. DESIGN: A retrospective, observational cohort study of the National
      CF Patient Registry between the years 1990 to 1999. PATIENTS: The Registry
      contained data on 28,858 patients with CF observed over 10 years at CF centers
      across the United States. RESULTS: Massive hemoptysis occurred with an average
      annual incidence of 0.87% and in 4.1% of patients overall. There was no increased
      occurrence by sex, but it was more prevalent in older patients (mean age, 24.2 +/
      8.7 years [+/- SD]) with more severe pulmonary impairment (nearly 60% of
      patients who had an episode of massive hemoptysis had FEV1 < 40% predicted). The
      principal risks associated with an increased occurrence of massive hemoptysis
      included the presence of Staphylococcus aureus in sputum cultures (odds ratio
      [OR], 1.3) and diabetes (OR, 1.1). There was an increased morbidity (eg,
      increased hospitalizations and hospital days) and an increased 2-year mortality
      following massive hemoptysis. CONCLUSION: Massive hemoptysis is a serious
      complication in CF patients, occurring more commonly in older patients with more
      advanced lung disease. Nearly 1 in 100 patients will have this complication each
      year. There is an attributable mortality to the complication and considerable
      morbidity, resulting in increased health-care utilization and a measurable
      decline in lung function.

PMID- 16100162
TI  - Quality-of-life determinants in patients with clinically stable bronchiectasis.
AB  - STUDY OBJECTIVE: To determine the most important variables influencing health
      related quality of life (HRQL) in patients with clinically stable bronchiectasis
      (SB). DESIGN: Cross-sectional study. PATIENTS AND INTERVENTIONS: A total of 86
      patients (mean age, 69.5 years; SD, 8.9 years; 64% male) with SB were included.
      Data were collected on general patient characteristics, symptoms, laboratory
      findings, the extent of bronchiectasis, functional variables, medication in acute
      or stable phases, and the number of exacerbations. All patients completed the St.
      George Respiratory Questionnaire (SGRQ). Univariate and multivariate analyses
      were performed to identify the variables significantly influencing HRQL in these
      patients. RESULTS: Different clinical parameters (sputum, dyspnea, cough, and
      wheezing), spirometric variables, and laboratory parameters (fibrinogen), as well
      as the extent of bronchiectasis, medication, and the number of exacerbations were
      significantly correlated to the total questionnaire score, although only dyspnea
      (r2 = 0.43, p < 0.0001), FEV1 (r2 = 0.33, p < 0.0001), and daily sputum
      production (r2 = 0.2, p < 0.004) were independently correlated to the total
      score, globally explaining 55% of the total score variability. Systemic steroid
      treatment of exacerbations (r2 = 0.17, p < 0.028) and the habitual presence of
      coughing (r2 = 0.22, p < 0.004) and wheezing (r2 = 0.16, p < 0.013) were in turn
      independently correlated to the activity and symptoms subscales, respectively.
      CONCLUSION: Dyspnea, FEV1, and sputum production are the strongest conditioning
      factors of HRQL in patients with clinically SB.

PMID- 16100163
TI  - Smoking in contemporary American cinema.
AB  - OBJECTIVE: The true prevalence of smoking among characters portrayed in the
      movies is unknown. This study examines this prevalence objectively. DESIGN: The
      top 10 movies on the weekly box office charts were reviewed. Whether or not the
      top five characters in these movies smoked, was documented. It was determined
      prior to the start of the study that 300 male characters and 300 female
      characters were needed to detect any significant difference. A total of 447
      movies, composed of 193 movies rated restricted (R) [children < 17 years of age
      must be accompanied by an adult], 131 movies rated PG13 for parental guidance
      suggested for children < 13 years of age (PG) and 123 movies rated PG for
      parental guidance suggested, were examined until the sample size was reached.
      RESULTS: Smoking prevalence is the same in contemporary American movies and in
      the general US population (23.3% vs 24.8%, respectively). However, there was more
      smoking in these movies among men than among women (25.5% vs 20.5%, respectively;
      p < 0.006), among antagonists than among protagonists (35.7% vs 20.6%,
      respectively; p < 0.001), lower vs middle vs upper socioeconomic class (SEC)
      [48.2%, 22.9%, and 10.5%, respectively; p < 0.001], among independent vs studio
      movies (46.2% vs 18.2%, respectively; p < 0.001); and among R-rated vs PG13-rated
      vs PG-rated movies (37.3%, 16.2%, and 8.1%, respectively; p < 0.001). In R-rated
      movies, and in both subcategories of R-rated studio movies and R-rated
      independent movies, smoking prevalence is higher than in the US population
      (37.3%, 30.5%, and 50.6% vs 24.8%, respectively; p < 0.001 for all).
      Additionally, compared to the US population, men, women and lower SEC members
      smoke more in R-rated movies, R-rated studio movies, and R-rated independent
      movies. In R-rated movies, antagonists smoke more than protagonists (43.9% vs
      35.8%, respectively; p < 0.001), and whites smoke more than nonwhites (38.3% vs
      26.4%, respectively; p < 0.001). In R-rated studio movies, antagonists smoke more
      than protagonists (42.6% vs 26.6%, respectively; p < 0.001), and men smoke more
      than women (32.0% vs 27.9%, respectively; p = 0.03). In R-rated independent
      movies, whites smoke more than nonwhites (51.8% vs 40.5%, respectively; p <
      0.001). Smoking prevalence is higher in R-rated independent movies than in R
      rated studio movies (50.6% vs 30.5%, respectively; p < 0.001). Smoking prevalence
      is also higher in R-rated independent movies than in R-rated studio movies in
      subcategories of men (32.0% vs 49.8%, respectively; p < 0.001), women (21.8 vs
      51.8%, respectively; p < 0.001), protagonists (26.6% vs 51.6%, respectively; p <
      0.001), whites (31.5% vs 51.8%, respectively; p < 0.001), nonwhites (24.7% vs
      40.5%, respectively; p < 0.001), and all three SECs. CONCLUSIONS: In contemporary
      American cinema, the smoking prevalence is higher for men, antagonistic
      characters, lower SEC, independent movies, and R-rated movies. Smoking prevalence
      is higher than in the general US population in R-rated movies, and in both its
      subcategories of R-rated studio movies and R-rated independent movies. There is
      more smoking in R-rated independent movies than in R-rated studio movies. Smoking
      in contemporary American cinema is associated with male sex, lower SEC, and
      antagonistic (ie, bad) characters.

PMID- 16100164
TI  - Disturbed right ventricular diastolic function in patients with systemic
      sclerosis: a Doppler tissue imaging study.
AB  - BACKGROUND: Cardiopulmonary involvement in patients with systemic sclerosis (SSc)
      carries a poor prognosis, mainly due to pulmonary hypertension and right-heart
      failure. To date, right ventricular (RV) involvement has not been studied in
      detail. We therefore assessed RV function in patients with SSc and related the
      findings to the clinical features of the disease. METHOD: Twenty-six consecutive
      patients (21 women) with SSc (mean age, 56 +/- 15 years [+/- SD]) and 25 healthy,
      age-matched control subjects (21 women) were studied. Doppler echocardiography
      including Doppler tissue imaging was used to evaluate cardiac function. Pulmonary
      function was also studied. RESULTS: Compared with control subjects, RV free wall
      thickness (5.8 +/- 1.7 mm vs 3.7 +/- 1.1 mm, p < 0.001) and right atrial (RA)
      systolic area (15.9 +/- 3.7 cm2 vs 13.0 +/- 2.3 cm2, p < 0.01) were increased in
      patients with SSc, while the global early diastolic/atrial component velocity
      ratio was reduced (1.2 +/- 0.4 vs 1.7 +/- 0.6, p < 0.01). The global isovolumic
      relaxation time (IVRT) [64 +/- 23 ms vs 39 +/- 13 ms, p < 0.001] and regional
      IVRT (83 +/- 40 ms vs 46 +/- 24 ms, p < 0.001) were prolonged in patients vs
      control subjects, whereas the RV global filling time was reduced (454 +/- 122 ms
      vs 548 +/- 104 ms, p < 0.01). RV systolic function and pulmonary pressures at
      rest were similar in the two groups, but the pulmonary artery acceleration time
      was reduced (119 +/- 34 ms vs 141 +/- 29 ms, p < 0.05) in patients compared to
      control subjects. Left ventricular function did not differ between the two
      groups. CONCLUSION: Patients with SSc exhibit altered RV diastolic function
      together with an increase in RV wall thickness and RA area. These findings appear
      to be early markers of RV disturbance, probably in response to intermittent
      pulmonary arterial hypertension.

PMID- 16100165
TI  - The impact of hospital-acquired infections on the microbial etiology and
      prognosis of late-onset prosthetic valve endocarditis.
AB  - STUDY OBJECTIVES: To study the changing etiology of prosthetic valve endocarditis
      (PVE) and the impact of nosocomial acquisition of the infection on prognosis in a
      single hospital. METHODS: Retrospective review of 121 cases of PVE during a
      period of 34 years. Two different periods (the period from 1970 to 1986 [P1], and
      the period from 1987 to 2003 [P2]) were analyzed. RESULTS: During P1, 58 patients
      with PVE were treated (30 early PVE and 28 late PVE); during P2, 63 patients with
      PVE were treated (13 early PVE and 50 late PVE). The frequency of early-onset PVE
      decreased from 0.94% in P1 to 0.34% in P2 (p < 0.001), but the incidence rate of
      late-onset PVE did not change (0.33% and 0.42% per year, respectively). The
      microbiology of early PVE changed over the years: Gram-negative bacilli decreased
      from 40% during P1 to 7.7% in P2 (p = 0.033). Staphylococci remained the main
      causes of early PVE in both periods. The microbial etiology of late PVE also
      changed over the years with enterococci and Staphylococcus aureus as the leading
      causes during P2. Streptococcus viridans decreased from a leading position to a
      fourth position. Methicillin-resistant S aureus endocarditis appeared first in
      1992. Eleven cases of late-onset PVE in P2 were hospital acquired (22%). In
      comparison, only two cases (7.1%) of hospital-acquired, late-onset PVE were seen
      in P1 (p = 0.11). Mortality of early-onset PVE decreased from 80% in P1 to 46% in
      P2 (p = 0.026). The overall mortality of late-onset PVE did not change between
      periods: 39% vs 34%. Mortality associated with nosocomial PVE in P2 was 63.6% (7
      of 11 patients). In comparison, the mortality of community-acquired cases was
      25.6% (10 of 39 patients; p = 0.03). In the multivariate analysis, the presence
      of comorbidities and hospital acquisition were associated with an excess of
      mortality (odds ratio [OR], 13.9; 95% confidence interval [CI], 1.23 to 158 [p =
      0.033]; and OR, 10.8; 95% CI, 2.16 to 54.7 [p = 0.0037], respectively).
      CONCLUSION: Although the mortality associated with early-onset PVE has
      significantly decreased, in this series the mortality of patients with late-onset
      PVE remained high due mainly to an increasing number of patients with
      comorbidities who acquired the infection during admission for other diseases.

PMID- 16100166
TI  - Nosocomial endocarditis in a tertiary hospital: an increasing trend in native
      valve cases.
AB  - INTRODUCTION: Changes in the etiology, epidemiology, and outcome of infective
      endocarditis (IE) have been observed in recent years. Newer invasive therapeutic
      interventions have increased the risk of bacteremia and nosocomial endocarditis
      in the population at risk. A retrospective analysis of hospital-acquired IE cases
      was performed in a tertiary hospital during 1985 to 1999. MATERIAL AND METHODS:
      Cases included were those classified as "probable" or "definite" by the IE
      diagnostic criteria of Durack. Nosocomial acquisition was considered if diagnosis
      was made > 72 h after hospital admission and there was no evidence that IE was
      present at the time of admission. Patients receiving a diagnosis within 60 days
      of a previous hospital admission were also classified as nosocomial, when a risk
      procedure for bacteremia was performed, or when any predisposing factor for IE
      was present during hospitalization. Early prosthetic valve endocarditis (PVE)
      cases (< 1 year) were excluded from the analysis. Clinical characteristics,
      etiology, predisposing cardiac condition, source of infection, and outcome were
      analyzed. Results were compared with those obtained in community-acquired cases.
      RESULTS: Of 493 cases of IE diagnosed over 15 years, 38 were considered to be
      hospital acquired. Twenty-eight cases were native valve endocarditis (NVE) in non
      IV drug user patients, and 10 cases were late PVE. Overall, the most frequent
      microorganisms involved were staphylococci (58%). The main sources of infection
      were intravascular procedures or catheter-related infections (55%). When
      nosocomial NVE cases were compared with community-acquired cases, mortality was
      greater (29% vs 9.7%) in hospital-acquired endocarditis. Analysis of time trends
      showed an increased rate of nosocomial cases in NVE throughout the years of the
      study. CONCLUSIONS: In NVE, the number of cases that are hospital acquired has
      been increasing during the last 15 years. These cases are frequently associated
      with invasive intravascular procedures or IV catheter-related infections. Most
      patients have a previous valvulopathy that predisposes to IE. The spectrum of
      microorganisms involved is different from the community-acquired cases. Also, the
      outcome of endocarditis is worse in nosocomial NVE patients.

PMID- 16100167
TI  - ST-segment depression in lead aVR: a useful predictor of impaired myocardial
      reperfusion in patients with inferior acute myocardial infarction.
AB  - STUDY OBJECTIVE: During inferior acute myocardial infarction (AMI), the ECG lead
      aVR is frequently ignored, and therefore its clinical significance remains
      unclear. We examined the relation between ST-segment deviation seen in lead aVR
      on ECGs obtained at hospital admission and myocardial reperfusion in patients who
      have experienced recanalized inferior AMIs. DESIGN AND SETTING: Retrospective
      study. PATIENTS: A total of 225 patients with inferior AMIs in whom Thrombolysis
      in Myocardial Infarction grade 3 flow was achieved within 6 h after symptom
      onset. MEASUREMENTS AND RESULTS: Patients were classified as follows according to
      ST-segment deviation in lead aVR on an ECG obtained at hospital admission: group
      A, 103 patients with no ST-segment depression; group B, 80 patients with ST
      segment depression of < or = 1.0 mm; and group C, 42 patients with ST-segment
      depression of > 1.0 mm. There were no differences in time from symptom onset to
      hospital admission or in the culprit lesion among the three groups. The degree of
      ST-segment elevation in leads II, III, aVF, V5, or V6, the degree of ST-segment
      depression in leads V1 to V4, and the sum of ST-segment deviation in these leads
      were lowest in group A and highest in group C. In groups A, B, and C, the
      incidence of impaired myocardial reperfusion, defined as myocardial blush grade
      0/1, was 2%, 23%, and 67%, respectively (p < 0.001). The sensitivity and negative
      predictive values of ST-segment depression in lead aVR for impaired myocardial
      reperfusion were higher than those based on other ECG variables. Multivariate
      analysis showed that the degree of ST-segment depression in lead aVR was an
      independent predictor of impaired myocardial reperfusion (odds ratio 8.41; 95%
      confidence interval, 2.96 to 23.9; p < 0.001). CONCLUSIONS: We conclude that the
      degree of ST-segment depression in lead aVR is a useful predictor of impaired
      myocardial reperfusion in patients who have experienced inferior AMIs.

PMID- 16100168
TI  - Hypoxia-inducible factor 1alpha polymorphism and coronary collaterals in patients
      with ischemic heart disease.
AB  - STUDY OBJECTIVES: Marked variability exists in coronary artery collaterals in
      patients with ischemic heart disease. Although multiple factors are thought to
      play a role in collateral development, the contribution of genetic factors is
      largely unknown. Hypoxia inducible factor 1 (HIF-1), a transcriptional activator
      that functions as a master regulator of oxygen homeostasis, is one possible
      genetic factor that could play an important role in modulating collateral
      development. DESIGN, SETTING, AND PARTICIPANTS: Collateral vessels were
      determined in 100 patients with > or = 70% narrowing of at least one coronary
      artery without acute myocardial infarction or prior revascularization. DNA was
      genotyped for the presence of a single nucleotide (C to T) polymorphism that
      changes residue 582 of HIF-1alpha from proline to serine. MEASUREMENTS AND
      RESULTS: The frequency of the T allele was significantly higher among patients
      without collaterals compared to patients with collaterals (0.188 vs 0.037, p <
      0.001). In multivariate analyses, two variables affecting collateral formation
      were detected: two- or three-vessel coronary artery disease was a significant
      positive predictor (odds ratio [OR], 4.17; 95% confidence interval [CI], 1.61 to
      10.8; p = 0.001), whereas the presence of HIF-1alpha genotype CT or TT was a
      negative predictor (OR, 0.19; 95% CI, 0.04 to 0.84; p = 0.03). CONCLUSIONS: These
      data suggest that variations in HIF-1alpha genotype may influence development of
      coronary artery collaterals in patients with significant coronary artery disease.

PMID- 16100169
TI  - Influence of age on gender differences in the management of acute inferior or
      posterior myocardial infarction.
AB  - STUDY OBJECTIVES: To assess the effect of gender on the in-hospital management of
      patients with acute inferior or posterior myocardial infarction (MI). DESIGN:
      Retrospective analysis of clinical records. Gender differences in management and
      prognosis were assessed by stepwise multiple logistic regression analysis.
      SETTING: University, large-volume, tertiary hospital. PATIENTS: We studied 1,178
      consecutive patients admitted to our coronary care unit with an acute inferior or
      posterior MI, and evaluated the influence of gender on clinical management and
      outcome. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Women were older (73
      years vs 66 years), had a higher prevalence of diabetes and hypertension,
      presented later (8 h vs 6 h after symptom onset), and had a higher in-hospital
      mortality rate (26% vs 9%) [all p values < 0.01]. Women underwent reperfusion
      therapy (45% vs 61%, p < 0.01), noninvasive studies (30% vs 62%, p < 0.001), and
      coronary angiography (34% vs 48%, p < 0.01) less often than men. Multivariable
      analysis revealed that female gender was an independent predictor of a lower use
      of noninvasive studies (odds ratio [OR], 0.41; 95% confidence interval [CI], 0.24
      to 0.63; p < 0.005) and coronary angiography (OR, 0.59; 95% CI, 0.37 to 0.93; p =
      0.02). A significant interaction between age and gender was found (p = 0.002);
      therefore, women > or = 75 years old had a much lower probability of undergoing
      noninvasive tests and coronary angiography than men of the same age. CONCLUSION:
      Despite their worse prognosis, women undergo noninvasive studies and coronary
      angiography less frequently than men after an acute inferior or posterior MI. The
      gender gap increases in patients > or = 75 years old.

PMID- 16100170
TI  - Clinical factors associated with persistent pericardial effusion after successful
      primary coronary angioplasty.
AB  - STUDY OBJECTIVE: To evaluate the incidence and clinical factors related to the
      persistence of infarct-associated pericardial effusion (PE) after primary
      angioplasty. DESIGN: Consecutive case-series analysis. SETTING: Coronary care
      unit in a university hospital. PATIENTS: Three hundred ninety-one consecutive
      patients with acute myocardial infarction (AMI) who underwent successful primary
      percutaneous transluminal coronary angioplasty (PTCA) at hospital admission.
      INTERVENTIONS: Coronary angiography and primary PTCA on hospital admission and
      serial echocardiography. MEASUREMENTS AND RESULTS: The status of coronary flow
      before and after primary PTCA was evaluated by coronary angiography at hospital
      admission, while PE was studied by echocardiography within 24 h of admission and
      1 month after the onset of AMI. PE was present in the acute phase in 76 patients
      (19%), and patients with PE had a significantly higher incidence of in-hospital
      death than those without PE (11% vs 2%, p < 0.001). Among 68 patients who had PE
      in the acute phase and underwent echocardiography 1 month later, PE persisted to
      1 month after the onset of AMI (persistent PE) in 26 patients (38%). Patients
      with persistent PE had a significantly higher incidence of pericardial rub (p =
      0.010), Killip class > 1 (p = 0.025), no reflow after PTCA (p = 0.026), lower
      incidence of collaterals (p = 0.024), and tended to have higher peak creatine
      kinase (CK) [p = 0.05] levels than those with transient PE. When five variables
      (peak CK, collaterals, no reflow, pericardial rub, and Killip class > 1) were
      used in the multivariate analysis, pericardial rub (p = 0.023; odds ratio [OR],
      5.45), absence of collaterals (p = 0.011; OR, 0.16), and Killip class > 1 (p =
      0.027; OR, 3.80) were the significant variables related to persistent PE.
      CONCLUSIONS: PE remains a relatively common complication of AMI even in the era
      of reperfusion therapy and is associated with increased mortality. Furthermore,
      the presence of a pericardial rub, Killip class > 1, and absence of collateral
      flow in the early phase of the infarct are associated with persistence of the PE
      to 1 month after the onset of AMI.

PMID- 16100171
TI  - Revascularization of left anterior descending coronary artery in patients with
      single and multivessel disease: comparison between off-pump internal thoracic
      artery and drug-eluting stent.
AB  - STUDY OBJECTIVES: The left anterior descending artery (LADA), particularly when
      the proximal segment of the vessel is involved, is a challenging area for
      percutaneous coronary interventions (PCIs); therefore, coronary artery bypass
      grafting is often considered and sometimes performed even in patients with single
      vessel disease involving the LADA. This study compares mid-term results of LADA
      revascularization with a drug-eluting stent (DES), with off-pump coronary artery
      bypass grafting (OPCAB) in patients with single-vessel or multivessel coronary
      artery disease (CAD). DESIGN: Matched-groups, retrospective cohort comparison
      between the DES and OPCAB. PATIENTS: From June 2002 to December 2003, 354
      patients underwent myocardial revascularization of the LADA by OPCAB, and 168 by
      DES. After matching for age, sex, and extent of CAD, two groups (116 patients
      each) were used to compare the two revascularization modalities. The groups were
      similar; however, an ejection fraction of <30%, old myocardial infarction, and
      use of an intraaortic balloon pump were more prevalent in the OPCAB group.
      RESULTS: The average number of coronary vessels treated per patient in the two
      groups was similar (OPCAB, 1.97; DES, 1.6; p = 0.581). The 30-day mortality rate
      was 0.9% in the OPCAB group and 0% in the DES group (p = 0.329). The mean
      duration of follow-up was 12 months. There was one late death in each group.
      Angina returned in 31% of patients in the DES group and in 11.2% of the patients
      in the OPCAB group (p = 0.001). There were 12 reinterventions in the DES group
      compared to three reinterventions in the surgical group (p = 0.020). The only
      independent predictor (Cox proportional hazards regression model) of the return
      of angina (risk ratio [RR], 3.36; 95% confidence interval [CI], 1.57 to 7.14) and
      reintervention (RR, 3.9; 95% CI, 1.34 to 11.24) was assignment to the DES group.
      CONCLUSIONS: The mid-term clinical outcome of OPCAB in patients with CAD,
      including multivessel disease, was better than that for PCIs with only one DES
      used in patients with similar extents of CAD.

PMID- 16100172
TI  - Enhanced coronary calcification determined by electron beam CT is strongly
      related to endothelial dysfunction in patients with suspected coronary artery
      disease.
AB  - BACKGROUND: Coronary artery calcification determined by electron beam CT (EBCT)
      is strongly associated with total plaque burden but is not related to systemic
      vascular inflammation. AIMS: We sought to test the hypothesis that enhanced
      coronary artery calcification, a marker of atherosclerosis and plaque burden, was
      related to endothelial dysfunction in patients with suspected coronary artery
      disease (CAD). METHODS AND RESULTS: One hundred twenty-four subjects with
      suspected CAD were enrolled. Coronary artery calcification was detected by EBCT.
      A noninvasive method of brachial ultrasound was used to measure endothelium
      dependent flow-mediated vasodilation (FMD) and endothelium-independent
      nitroglycerin-mediated vasodilation (NMD). Serum high-sensitivity C-reactive
      protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) levels were also
      determined. Of the 124 patients, the calcium scores ranged from 0 to 4,394. All
      subjects were classified into three groups according to coronary calcium scores:
      group 1, score 0 (n = 26); group 2, scores 1 to 199 (n = 50); group 3, scores >
      or = 200 (n = 48). There was an inverse association between the degree of
      coronary artery calcification and the endothelium-dependent FMD in the three
      groups (6.9 +/- 0.6% vs 5.3 +/- 0.3% vs 3.7 +/- 0.3%, respectively; p < 0.001)
      but not the endothelium-independent NMD. Besides, no significant difference in
      serum levels of hsCRP and MCP-1 were found among the three groups. However, both
      the serum levels of hsCRP and MCP-1 were correlated significantly with
      endothelium-dependent FMD (r = - 0.211, p = 0.019; and r = - 0.188, p = 0.037,
      respectively). By multivariate analysis, enhanced coronary calcification was a
      strong independent predictor of endothelial dysfunction (p < 0.001). CONCLUSION:
      Enhanced coronary artery calcification strongly predicted endothelial dysfunction
      in patients with suspected CAD. Also, serum levels of hsCRP and MCP-1 were
      significantly correlated with endothelial function. These findings suggested that
      both calcium deposition and inflammation were involved in endothelial
      dysfunction.

PMID- 16100173
TI  - The management of chest tubes in patients with a pneumothorax and an air leak
      after pulmonary resection.
AB  - BACKGROUND: Placing chest tubes to water seal is superior for patients with an
      air leak, but when a patient has a pneumothorax and an air leak the best chest
      tube setting is unknown. METHODS: This is a retrospective analysis of a
      prospective database on a consecutive series of patients who had a pneumothorax
      and air leak on the same day. Patients underwent elective pulmonary resection by
      one surgeon and had their chest tubes placed to water seal on postoperative day
      1. Daily chest radiographs were obtained, and the size of the pneumothorax and
      air leak were measured. Tubes were left on seal unless there was a symptomatic
      enlarging pneumothorax or subcutaneous emphysema (defined as failing water seal).
      The primary objective was to evaluate the efficacy of water seal. We also wanted
      to identify risk factors that predicted failure of water seal. RESULTS: There
      were 838 patients > or = 21 years old who underwent elective pulmonary resection,
      and 86 patients (10%) had an air leak and a concomitant pneumothorax on the same
      day. Fourteen patients (16%) failed water seal. Multivariate analysis showed that
      a large air leak (greater than or equal to expiratory 3 in our classification
      system; odds ratio [OR], 16.5; p < 0.001) and a pneumothorax > 8 cm in size (OR,
      4.9; p < 0.005) were predictors of failing water seal. CONCLUSIONS: Keeping chest
      tubes on water seal is safe for most patients with an air leak and a
      pneumothorax. However, if the leak or pneumothorax is large, then subcutaneous
      emphysema or an expanding symptomatic pneumothorax is more likely. A prospective
      randomized trial is needed to compare water seal to suction in these patients.

PMID- 16100174
TI  - Nasal-continuous positive airway pressure reduces pulmonary morbidity and length
      of hospital stay following thoracoabdominal aortic surgery.
AB  - STUDY OBJECTIVES: Patients who undergo surgical repair of thoracoabdominal aortic
      aneurysms have a high risk for the development of respiratory complications,
      which cause significant postoperative morbidity and prolong hospitalization,
      compared to patients who undergo other types of surgery. We studied whether
      prophylactic noninvasive application of nasal continuous positive airway pressure
      (nCPAP) administered via a facemask immediately after extubation may reduce
      pulmonary morbidity and shorten the length of hospitalization. DESIGN:
      Prospective randomized clinical trial. SETTING: Surgical ICU of a university
      hospital. PATIENTS: Fifty-six patients following elective prosthetic replacement
      of the thoracoabdominal aorta, of whom 6 patients were excluded because they had
      received prolonged mechanical ventilation. INTERVENTIONS: Following extubation in
      the ICU, nCPAP was applied for 12 to 24 h at an airway pressure of 10 cm H2O to
      patients in the study group (n = 25). Subjects in the control group (n = 25)
      received standard treatment including intermittent nCPAP (10 cm H2O for 10 min)
      every 4 h. MEASUREMENTS AND RESULTS: In the study group, nCPAP was applied for a
      mean (+/- SD) duration of 23 +/- 3 h at an airway pressure of 10 +/- 1 cm H2O,
      which improved pulmonary oxygen transfer without altering hemodynamics (ie, heart
      rate, mean arterial BP, and central venous pressure). The application of nCPAP
      was associated with fewer pulmonary complications (Pa(O2)/fraction of inspired
      oxygen [F(IO2)] <100, atelectasis, pneumonia, reintubation rate) compared to the
      control group (7 of 25 patients vs 24 of 25 subjects, respectively; p = 0.019).
      The mean duration of intensive care treatment tended to be shorter in the study
      group compared to the control group (8 +/- 1 vs 12 +/- 2 days, respectively;
      difference not significant), while the mean length of hospital stay was shorter
      with nCPAP therapy (22 +/- 2 vs 34 +/- 5 days, respectively; p = 0.048).
      CONCLUSIONS: The prophylactic application of nCPAP at airway pressures of 10 cm
      H2O significantly reduced pulmonary morbidity and length of hospital stay
      following the surgical repair of thoracoabdominal aortic aneurysms. Thus, it can
      be recommended as a standard treatment procedure for this patient group.

PMID- 16100175
TI  - The relation between surgeon volume and outcome following off-pump vs on-pump
      coronary artery bypass graft surgery.
AB  - STUDY OBJECTIVE: Off-pump coronary artery bypass graft (CABG) surgery has been
      recently reintroduced into clinical practice. In light of the relatively low
      level of experience of most cardiac surgeons with off-pump CABG surgery, and the
      exceptional technical challenge of working on a "beating heart," off-pump CABG
      surgery presents a unique opportunity to explore the effect of surgeon case
      volume on surgical outcome after controlling for the effects of patient case mix
      and hospital volume. DESIGN: A retrospective cohort study analyzing the
      association between surgeon volume and in-hospital mortality rate for off-pump
      and on-pump CABG surgery using random-effects logistic regression modeling.
      SETTING AND PATIENTS: The analyses were based on the New York State clinical CABG
      surgery registry. The study sample consisted of 36,930 patients undergoing
      isolated CABG surgery between 1998 and 1999 that was performed by 181 surgeons at
      33 hospitals. INTERVENTIONS: None. RESULTS: There is no association between the
      number of CABG procedures performed off-pump by an individual surgeon and in
      hospital mortality rates (p = 0.93) after controlling for hospital CABG surgery
      volume and patient-level risk factors. There is also no association between the
      off-pump CABG surgery mortality rate and the total number of both off-pump and on
      pump CABG surgery cases (p = 0.78). In the on-pump CABG surgery cohort, surgeons
      performing a high volume of CABG procedures had significantly lower risk-adjusted
      mortality rates among their patients compared to those performing a very low
      volume, a low-volume, and a medium volume of CABG procedures (p < 0.006).
      CONCLUSION: For off-pump CABG surgery, surgeons performing a high volume of
      procedures do not have better mortality outcomes than those performing a low
      volume of procedures. However, higher surgeon case volumes are associated with
      lower mortality rates for on-pump CABG surgery. The absence of a volume-outcome
      association for off-pump CABG surgery is especially surprising in light of the
      more technically demanding nature of off-pump CABG surgery compared to on-pump
      CABG surgery.

PMID- 16100176
TI  - Cardioprotective effects of acute normovolemic hemodilution in patients
      undergoing coronary artery bypass surgery.
AB  - STUDY OBJECTIVES: We hypothesized that lowering blood viscosity with acute
      normovolemic hemodilution (ANH) would confer additional cardioprotection in
      patients undergoing coronary artery bypass surgery (CABG) with aortic cross
      clamping. DESIGN: In a prospective, randomized controlled trial, we studied the
      efficacy of ANH in anesthetized patients prior to cardiopulmonary bypass for the
      prevention of myocardial injuries. SETTING: Cardiac surgical center in a
      university hospital. PATIENTS AND METHODS: Patients scheduled to undergo elective
      CABG entered the study protocol and were randomly allocated to one of two groups:
      ANH (n = 43 patients) or standard care management (n = 41 patients). In the ANH
      group, the whole-blood/colloid exchange was aimed to achieve a hematocrit value
      of 28%. All patients were managed with standard myocardial preservation
      techniques including cold-blood cardioplegia and anesthetic preconditioning. The
      outcome measures included the release of myocardial enzymes (plasma troponin I
      and creatinine phosphokinase), perioperative hemodynamic changes, need for
      pharmacologic cardiovascular support, and cardiac complications. RESULTS: In the
      hemodilution group, the postoperative release of troponin I (mean peak plasma
      concentration, 1.4 ng/mL; 95% confidence interval, 1.0 to 1.8) and myocardial
      fraction of creatine kinase (mean, 29 U/L; 95% confidence interval, 23 to 35)
      were significantly lower than in the control group (mean, 3.8 ng/mL; 95%
      confidence interval, 3.2 to 4.5; and 71 U/L; 95% confidence interval, 53 to 89).
      Requirement for inotropic support was significantly lower in the protocol
      patients (7 of 41 patients vs 15 of 39 patients), and fewer patients presented
      with either atrial fibrillation, atrioventricular conduction blockade, or
      combined disorders (12 of 41 patients vs 26 of 39 patients, p < 0.05).
      CONCLUSIONS: In addition to conventional myocardial preservation techniques,
      preoperative ANH achieved further cardiac protection in patients undergoing on
      pump myocardial revascularization.

PMID- 16100177
TI  - Stroke volume and pulse pressure variation for prediction of fluid responsiveness
      in patients undergoing off-pump coronary artery bypass grafting.
AB  - STUDY OBJECTIVES: Stroke volume variation (SVV) and pulse pressure variation
      (PPV) determined by the PiCCOplus system (Pulsion Medical Systems; Munich,
      Germany) may be useful dynamic variables in guiding fluid therapy in patients
      receiving mechanical ventilation. However, with respect to the prediction of
      volume responsiveness, conflicting results for SVV have been published in cardiac
      surgery patients. The goal of this study was to reevaluate SVV in predicting
      volume responsiveness and to compare it with PPV. DESIGN: Prospective
      nonrandomized clinical investigation. SETTING: University-based cardiac surgery.
      PATIENTS: Forty patients with preserved left ventricular function undergoing
      elective off-pump coronary artery bypass grafting. INTERVENTIONS: Volume
      replacement therapy before surgery. MEASUREMENTS AND RESULTS: Following induction
      of anesthesia, before and after volume replacement (6% hydroxyethyl starch
      solution, 10 mL/kg ideal body weight), hemodynamic measurements of stroke volume
      index (SVI), SVV, PPV, global end-diastolic volume index (GEDVI), central venous
      pressure (CVP) and pulmonary capillary wedge pressure (PCWP) were obtained. Also,
      left ventricular end-diastolic area index (LVEDAI) was assessed by
      transesophageal echocardiography. Prediction of ventricular performance was
      tested by calculating the area under the receiver operating characteristic (ROC)
      curves and by linear regression analysis; p < 0.05 was considered significant.
      All measured hemodynamic variables except heart rate changed significantly after
      fluid loading. GEDVI, CVP, PCWP, and LVEDAI increased, whereas SVV and PPV
      decreased. The best area under the ROC curve (AUC) was found for SVV (AUC =
      0.823) and PPV (AUC = 0.808); the AUC for other preload indexes ranged from 0.493
      to 0.636. A significant correlation with changes of SVI was observed for SVV (r =
      0.606, p < 0.001) and PPV (r = 0.612, p < 0.001) only. SVV and PPV were closely
      related (r = 0.861, p < 0.001). CONCLUSIONS: In contrast to standard preload
      indexes, SVV and PPV, comparably, showed a good performance in predicting fluid
      responsiveness in patients before off-pump coronary artery bypass grafting.

PMID- 16100178
TI  - Outcome of coronary artery bypass operations in patients with renal insufficiency
      with and without renal transplantation.
AB  - HYPOTHESIS: Renal insufficiency (RI) is associated with an increased risk of
      morbidity and mortality following coronary artery bypass graft (CABG) operations,
      particularly among patients who are dependent on dialysis. DESIGN AND SETTING: A
      retrospective analysis of data collected at a tertiary care center. PATIENTS: One
      hundred eighty-four consecutive patients with RI who underwent CABG surgery
      between 1992 and 2004. This group consisted of 152 patients with serum creatinine
      levels of > or = 1.7 mg/dL (group I) and 32 kidney transplant recipients (group
      II). Of the patients in group I, 90 were dialysis-free (subgroup IA) and 62 were
      dialysis-dependent (subgroup IB). MAIN OUTCOME MEASURES: Demographics,
      perioperative data, and outcomes for each of the three groups were evaluated and
      compared. RESULTS: Fifty-four percent of the patients were in New York Heart
      Association classes III and IV, 36% had unstable angina, and 21% had left main
      coronary disease. The mean ejection fraction was 38%. The median postoperative
      length of stay in the hospital was 10 days. Of the patients in group IB, 8%
      required reexploration for bleeding compared to 3% in groups IA and II (p <
      0.05). Dialysis was needed postoperatively in five patients in group IA and two
      patients in group II (5.7%). The raw operative mortality rate was 7.6% and was
      higher in group IB (9.7%) compared to groups IA and II (6.7% and 6.2%,
      respectively; p < 0.05). The actuarial 5-year survival rate was higher in group
      II compared to group I (79% vs 59%, respectively; p < 0.05). The difference in
      survival rates was more apparent between groups II and IB (79% vs 57%,
      respectively; p < 0.005). CONCLUSIONS: CABG is associated with an increased rate
      of perioperative complications and mortality in patients with RI. Dialysis
      dependence is a major risk factor for patients undergoing CABG surgery. However,
      with acceptable surgical results, dialysis patients should not be denied CABG
      surgery. A survival advantage is demonstrated among patients with previous kidney
      transplants compared to those patients who are dependent on dialysis.

PMID- 16100179
TI  - Prefixed equimolar nitrous oxide and oxygen mixture reduces discomfort during
      flexible bronchoscopy in adult patients: a randomized, controlled, double-blind
      trial.
AB  - STUDY OBJECTIVES: Flexible bronchoscopy (FB) is an invasive procedure associated
      with patient discomfort and frequent nose pain. A simple sedation procedure that
      does not require the intervention of an anesthetist is of interest. The aim of
      this prospective, randomized, double-blind study was to assess efficiency of
      nitrous oxide inhalation on the reduction of FB-induced discomfort in adult
      patients. DESIGN AND SETTINGS: Two hundred six patients were randomized to
      receive either a prefixed equimolar nitrous oxide/oxygen mixture (N2O) or a
      prefixed equimolar nitrogen and oxygen mixture (control). The primary outcome was
      stress as assessed by pulse rate and systemic BP during the procedure. Secondary
      outcomes were self-assessed pain using a visual analog scale (VAS) and patient
      satisfaction based on a questionnaire. Adverse events were recorded. RESULTS: A
      significant increase in BP was observed only in the control group (p = 0.003),
      while pulse rate values did not differ between the two groups. As assessed by the
      VAS, pain was lower in the N2O group as compared to placebo (p = 0.02). Nose pain
      and cough were also significantly reduced by N2O. Adverse events, mostly anxiety,
      were reported in 10 patients. CONCLUSION: These results indicate that equimolar
      N2O inhalation is efficient in reducing patient discomfort and may be an
      alternative to general anesthesia.

PMID- 16100180
TI  - Impact of rapid on-site cytologic evaluation during transbronchial needle
      aspiration.
AB  - STUDY OBJECTIVE: To determine the extent to which rapid on-site cytologic
      evaluation (ROSE) of transbronchial needle aspiration (TBNA) samples can safely
      and cost-effectively reduce the need for additional biopsy during bronchoscopy.
      SETTING: University Hospital in Long Island, NY. PATIENT AND METHODS: Forty-four
      bronchoscopies with TBNA, most of which utilized ROSE, were evaluated
      prospectively. The number and types of biopsies performed during each procedure
      were compared to a preprocedural algorithm to determine the impact of knowing
      ROSE results during the procedure. Bronchoscopies performed with and without ROSE
      were compared, as were bronchoscopies with diagnostic and nondiagnostic ROSE
      results. A cost analysis was performed comparing the Medicare reimbursement for
      ROSE to the savings of deferring multiple biopsies. RESULTS: Thirty-two
      bronchoscopies were performed with ROSE; 12 were performed without ROSE. Fewer
      biopsies were performed during bronchoscopies utilizing ROSE. Diagnostic yield,
      TBNA sensitivity and accuracy, and procedural time were similar between these two
      groups. CONCLUSIONS: ROSE during TBNA allows for deferring additional biopsy
      without loss in diagnostic yield, likely lowers procedural risk, and is cost
      effective.

PMID- 16100181
TI  - Subepithelial microvasculature in large airways observed by high-magnification
      bronchovideoscope.
AB  - BACKGROUND: The bronchial vasculature serves important functions and is modified
      in a variety of pulmonary and airway diseases. The remarkable ability of the
      bronchial vasculature to undergo remodeling has implications for disease
      pathogenesis. However, there is very little information on normal bronchial
      circulation. OBJECTIVES: The aim of this study was to obtain information on
      bronchial microvessels in large airways using a high-magnification
      bronchovideoscope. METHODS AND PATIENTS: Recently, we developed a high
      magnification bronchovideoscope (XBF-200HM3 [side-viewing type]) in cooperation
      with Olympus Medical Systems. This bronchovideoscope can provide information on
      the bronchial mucosa with a maximum magnification of 110 times. Between August
      2000 and July 2004, 26 patients without abnormalities in the large airways were
      enrolled into this study. Patients underwent conventional bronchoscopy and
      subsequent bronchoscopy with the high-magnification bronchovideoscope. After the
      bronchoscopic examination, we calculated the vessel area ratios and hemoglobin
      indexes of images made with the high-magnification bronchovideoscope by using
      appropriate software. In addition, we compared the findings obtained with the
      high-magnification bronchovideoscope of the 26 subjects with microscopic findings
      of autopsied tracheas of two patients without abnormalities. RESULTS: Many
      ramifying subepithelial microvessels of large airways were mainly observed in
      intercartilage and membranous portions, whereas only a few microvessels were seen
      in cartilage portions. Histologically, these subepithelial microvessels were
      thought to be distributed within approximately 800 and 500 microm beneath the
      surface of the intercartilage portions and membranous portions, respectively.
      Vessel area ratios of the intercartilage portions were significantly higher than
      those of the cartilage and membranous portions. The hemoglobin indexes of the
      intercartilage portions were significantly higher than those of the cartilage and
      membranous portions, and these indexes were also significantly higher in the
      membranous portion than in the cartilage portion. CONCLUSIONS: A dense
      concentration of subepithelial microvessels was mainly observed in the
      intercartilage portion, indicating an increase in submucosal circulation. This
      high-magnification bronchovideoscope is a useful tool for observing and
      evaluating the subepithelial microvessels in large airways.

PMID- 16100182
TI  - Bedside ultrasonography in the ICU: part 1.
AB  - Ultrasonography has become an invaluable tool in the management of critically ill
      patients. Its safety and portability allow for use at the bedside to provide
      rapid, detailed information regarding the cardiovascular system and the function
      and anatomy of certain internal organs. Echocardiography can noninvasively
      elucidate cardiac function and structure. This information is vital in the
      management hemodynamically unstable patients in the ICU. In addition,
      ultrasonography has particular value for the assessment and safe drainage of
      pleural and intra-abdominal fluid and the placement of central venous catheters.
      A new generation of portable, battery-powered, inexpensive, hand-carried
      ultrasound devices have recently become available; these devices can provide
      immediate diagnostic information not assessable by physical examination alone and
      allow for ultrasound-guided thoracocentesis, paracentesis, and central venous
      cannulation. This two-part article reviews the application of bedside
      ultrasonography in the ICU.

PMID- 16100183
TI  - Snoring imaging: could Bernoulli explain it all?
AB  - STUDY OBJECTIVES: To identify upper airway changes in snoring using CT scanning,
      to clarify the snoring mechanism, and to identify the key structures involved.
      PARTICIPANTS: Forty patients underwent CT examination of the head and neck region
      according to snoring habits; patients were classified into non-snoring (n = 14),
      moderately loud snoring (n = 13), and loud snoring (n = 13) groups. DESIGN:
      Comparative analysis. MEASUREMENTS: Using CT images, areas, the anteroposterior
      and transversal distances of the pharyngeal space at different levels, and the
      thickness and length of the soft palate and uvula and their angle against the
      hard palate were measured; evidence of impaired nasal passages was noted; the
      extent of pharyngeal inspiratory narrowing was the ratio between the area at the
      hard palate level and most narrow area; and expiratory narrowing was the ratio
      between the area behind the root of the tongue and the most narrow area. RESULTS:
      Greater pharyngeal inspiratory narrowing (p = 0.0015) proportional to the
      loudness of snoring (p = 0.0016), and a longer soft palate with uvula (p =
      0.0173) were significant for snoring. Impaired nasal breathing was significantly
      related (p = 0.029) only to the loud snoring group. The body mass index and age
      of snoring persons were also significantly higher. CONCLUSIONS: Snoring is
      associated with typical changes that can be revealed by CT scanning. Greater
      pharyngeal narrowing is the most important factor. Given the "Venturi tube" shape
      of the pharynx, the Bernoulli pressure principle plays a major role in snoring.
      The key structure in snoring is the soft palate: it defines the constriction and
      is sucked into vibrating by negative pressure that develops at this site. Its
      repetitive closures present an obstruction to breathing, producing the snoring
      sound, and should therefore be the target for causal treatment of snoring.
      Obstacles in the upper airway that increase negative inspiratory pressure could
      not be confirmed as important for the development of snoring, although they may
      increase its loudness.

PMID- 16100184
TI  - Inhaled beclomethasone dipropionate acutely stimulates dose-dependent growth
      hormone secretion in healthy subjects.
AB  - STUDY OBJECTIVES: It is well known that systemic administration of
      corticosteroids has a dual effect on growth hormone (GH) secretion in man: acute
      systemic administration stimulates GH release, whereas chronic administration
      consistently blocks it. In this study, we evaluate whether administration of
      inhaled corticosteroids could acutely stimulate GH secretion, and whether this
      effect could be dose related. DESIGN: Double-blind, placebo-controlled, crossover
      study. PARTICIPANTS: Eight normal male volunteers all recruited at our
      institution. INTERVENTIONS: Administration of increasing doses of inhaled
      beclomethasone dipropionate (BDP; range, 50 to 1,500 mug) or placebo.
      MEASUREMENTS AND RESULTS: Blood samples for GH determinations were collected at -
      15, 0, 60, 120, 180, 240, 300, and 360 min in relation to BDP or placebo
      administration. The results of this study show a peak GH secretion at 240 min
      after the administration of BDP at doses > 100 microg. The comparisons among the
      peaks obtained with increasing doses showed a dose-response effect on GH
      secretion, starting from 100 to 1,000 microg. BDP 1,500 microg did not induce a
      peak significantly different from that obtained with 1,000 microg. When we
      calculated the GH response to BDP as an area under the curve (micrograms per
      liter x 6 h), the data confirmed that GH secretion was elicited in a dose-related
      manner. CONCLUSIONS: Our data show that inhaled BDP at dose > 100 microg acutely
      stimulates GH secretion in a strictly dose-dependent manner. We propose this test
      as a surrogate for systemic absorption and as a valuable test to compare systemic
      effects among different inhaled steroids.

PMID- 16100185
TI  - Quantitative detection of lung cancer cells by fluorescence in situ
      hybridization: comparison with conventional cytology.
AB  - STUDY OBJECTIVE: The aim of this study was to clarify whether fluorescence in
      situ hybridization (FISH) can diagnose lung cancer in various clinical specimens
      in comparison with conventional cytology. DESIGN: Prospective study. SETTING:
      University hospital in a metropolitan area. PATIENTS: Fifty consecutive patients
      with abnormal chest radiography or CT scan findings were enrolled. The patients
      included 32 men and 18 women, with an average age of 64 years. The final
      definitive diagnosis was made by histologic examination, as follows: 38 primary
      lung cancers (24 adenocarcinomas, 8 squamous cell carcinomas, 2 large cell
      carcinomas, and 4 small cell carcinomas); 1 metastatic renal cell carcinoma; and
      11 benign lesions. METHODS: Four types of clinical specimens were analyzed. Cells
      obtained by transbronchial brushing and transbronchial fine-needle aspiration
      using a fiberoptic bronchoscope under fluoroscopy, CT scan-guided percutaneous
      needle biopsy, and bronchial washings. On every examination, duplicate slides
      were made for analyses of conventional cytology and FISH. RESULTS:
      Classifications according to conventional cytology were as follows: class I, 4
      patients; class II, 15 patients; class IIIa, 3 patients; class IIIb, 5 patients;
      and class V, 23 patients. A classification higher than class IIIb was considered
      to be positive for cancer. For cytology, we found no false-positive cases and 11
      false-negative cases. The specificity was 100%, and the sensitivity was 71.8%. By
      FISH, 34 cases showed aberrant copy numbers in either chromosome 3 or 17. We
      found no false-positive cases and five false-negative cases. The specificity was
      100%, and the sensitivity was 87.1%. CONCLUSION: The ability of FISH to detect
      aneusomic lung cancer cells is superior to conventional cytology for the
      diagnosis of lung cancer.

PMID- 16100186
TI  - Effects of azithromycin on clinical isolates of Pseudomonas aeruginosa from
      cystic fibrosis patients.
AB  - There is considerable interest in the use of azithromycin for the treatment of
      lung disease in patients with cystic fibrosis (CF). Although its mechanism of
      action as an inhibitor of bacterial protein synthesis has been well-established,
      it is less clear how azithromycin ameliorates the lung disease associated with
      Pseudomonas aeruginosa, which is considered to be resistant to the drug. We
      tested the effects of azithromycin on clinical isolates (CIs) from CF patients
      and compared them with laboratory reference strains to establish how this drug
      might interfere with the production of bacterial virulence factors that are
      relevant to the pathogenesis of airway disease in CF patients. Azithromycin
      inhibited P aeruginosa PAO1 protein synthesis by 80%, inhibiting bacterial growth
      and the expression of immunostimulatory exoproducts such as pyocyanin, as well as
      the gene products necessary for biofilm formation. In contrast, the effects of
      azithromycin on CIs of P aeruginosa were much more variable, due in large part to
      their slow growth and limited exoproduct expression. Culture supernatants for two
      of three clinical strains induced appreciable CXCL8 expression from cultured
      epithelial cells. Azithromycin treatment of the organisms inhibited 65 to 70% of
      this induction; azithromycin had no direct effect on the ability of either normal
      cells or CF epithelial cells to produce CXCL8. Azithromycin does decrease the P
      aeruginosa synthesis of immunostimulatory exoproducts and is likely to be most
      effective against planktonic, actively growing bacteria. This effect is less
      predictable against CIs than the prototypic strain PAO1.

PMID- 16100187
TI  - Fibroblast growth factor-2 induces recovery of pulmonary blood flow in canine
      emphysema models.
AB  - STUDY OBJECTIVES: Fibroblast growth factor (FGF)-2 is one of the most powerful
      angiogenic growth factors to be evaluated as an agent for the promotion of
      angiogenesis. The aim of this study is to investigate whether intratracheal
      administration of controlled-release FGF-2 microspheres restores pulmonary
      function in beagle dogs with emphysema. DESIGN: Randomized, controlled,
      experimental animal study. SUBJECTS: Eighteen Wister rats and 15 adult beagle
      dogs. METHODS: In the rat study, we compared the time profiles of the
      radioactivity remaining after intratracheal injection of 125I-labeled FGF-2,
      either incorporated with the controlled-release microspheres or as an aqueous
      solution. In the dog study, elastase-induced emphysema models were developed in
      10 animals, classified into the following three groups: control group (n = 5),
      emphysema model with empty microspheres-treated group (FGF - group, n = 5), and
      emphysema model with FGF-2 containing microspheres-treated group (FGF + group, n
      = 5). RESULTS: In the rat study, controlled-release microspheres maintained
      higher whole-lung FGF-2 concentrations after intratracheal administration. In the
      dog study, Pa(O2) in the FGF + group was significantly higher than in the FGF -
      group after treatment. Pulmonary perfusion dynamic MRI revealed significant
      improvement in the signal intensity of damaged lung with the FGF + group. Linear
      intercept of the FGF + group was significantly reduced than the FGF - group.
      CONCLUSION: Results indicate that intratracheal administration of FGF-2 induced
      an increase in pulmonary blood flow in the damaged lung and led to recovery of
      pulmonary function. The controlled-release microsphere system increased the
      effectiveness of FGF-2.

PMID- 16100188
TI  - Accuracy and limits of transpulmonary dilution methods in estimating
      extravascular lung water after pneumonectomy.
AB  - STUDY OBJECTIVES: The measurement of extravascular lung water index by double
      indicator (EVLWIdi) or the measurement of extravascular lung water index by
      transpulmonary thermodilution (EVLWItt) could be useful after pneumonectomy.
      Since pulmonary blood flow and volume are altered after pneumonectomy, the
      validity of these methods is uncertain. This study has compared measurements of
      EVLWIdi and EVLWItt with measurement of extravascular lung water index by
      gravimetry (EVLWIg) in a porcine model of pulmonary edema induced after right
      pneumonectomy. DESIGN: Randomized laboratory study. SETTING: Animal research
      laboratory. SUBJECTS: Twenty-seven female pigs; mean weight, 35 +/- 5 kg (+/-
      SD). INTERVENTIONS: The pigs were anesthetized, placed on mechanical ventilation,
      and allocated to a two-lung group (n = 10) or a right pneumonectomy group (n =
      17). EVLWIdi and EVLWItt were measured at baseline, 60 min after pneumonectomy,
      and 60 min after IV injection of oleic acid (OA). MEASUREMENTS AND RESULTS: There
      was a good correlation between EVLWIg and EVLWIdi values (r = 0.96, p < 0.0001 in
      the two-lung group; and r = 0.81, p = 0.02 in the pneumonectomy group). EVLWIdi
      underestimated EVLWIg in the two-lung group (- 3 mL/kg; 95% confidence interval
      [CI], - 7 to + 2 mL/kg) and in the pneumonectomy group (- 0.9 mL/kg; 95% CI, -
      3.3 to + 1.5 mL/kg). After pneumonectomy, EVLWItt decreased in mean by 27% and
      increased in mean by 70% after OA acid. There was a good correlation between
      EVLWIg and EVLWItt values (r = 0.96, p < 0.0001 in the two-lung group; and r =
      0.90, p < 0.0001 after pneumonectomy). EVLWItt slightly overestimated gravimetric
      value in the two-lung group (+ 1.5 mL/kg; 95% CI, - 1.5 to + 4.2 mL/kg) and
      largely overestimated gravimetric value after pneumonectomy (+ 5 mL/kg; 95% CI, +
      3.4 to + 6.8 mL/kg). CONCLUSION: Double-indicator and transpulmonary
      thermodilution methods could be useful in monitoring extravascular lung water
      index (EVLWI) after pneumonectomy, but transpulmonary thermodilution largely
      overestimates EVLWI.

PMID- 16100189
TI  - Efficacy of ultrasound in the diagnosis of pleurodesis in rabbits.
AB  - INTRODUCTION: The treatment of recurrent pleural effusion or recurrent
      pneumothorax frequently involves the creation of a pleurodesis. Ultrasound is
      being used more frequently to assess the presence of pleural fluid or
      pneumothorax. With ultrasound, the gliding sign displays the gliding of the
      visceral pleura over the parietal pleura during respiration. The absence of a
      gliding sign is indicative of a pneumothorax. HYPOTHESIS: We hypothesized that
      the presence of pleurodesis would be indicated by the absence of a gliding sign
      on ultrasound. METHODS: To create a pleurodesis, a single intrapleural injection
      of transforming growth factor-beta2 at a dosage of 1.70 microg/kg or doxycycline
      at a dosage of 10 mg/kg in a volume of 2.0 mL was administered randomly to one
      side of a New Zealand White rabbit. Prior to death on day 14 after intrapleural
      injection, all rabbits underwent an ultrasonic examination at three marked sites
      on each side of the chest. At each site, three ultrasonic features (gliding sign,
      pleural thickening, and pleural effusion) were evaluated and graded. The gliding
      sign was graded as follows: 0 = gliding sign definitely present, 1 = gliding sign
      questionable, 2 = gliding sign absent. RESULTS: In a preliminary study for
      developing skill in assessing the gliding sign, the correlation between the
      gliding sign and the pleurodesis score in 16 rabbits was highly significant (r =
      0.568, p = 0.02). In the subsequent main study with 18 additional rabbits, the
      correlation between the gliding sign score and the pleurodesis score was even
      better (r = 0.806, p = 0.00009). The gliding sign was definitely present on the
      noninjected side in all rabbits. CONCLUSIONS: The presence of a pleurodesis is
      indicated by the absence of a pleural guiding sign on ultrasound.

PMID- 16100190
TI  - The controversy of combination vs monotherapy in the treatment of hospitalized
      community-acquired pneumonia.
AB  - BACKGROUND: The majority of community-acquired pneumonia (CAP) patients (about
      80%) will be treated as outpatients, because therapy with a single agent will
      work. For the remaining 20% of patients requiring hospitalization, there is some
      growing debate regarding the efficacy of different management approaches. For
      hospitalized patients, monotherapy with a respiratory fluoroquinolone agent seems
      to be gaining popularity, but dual therapy combining a beta-lactam and an
      advanced macrolide still represents a good choice. Indeed, this regimen was
      recommended for all of the inpatient categories in the latest Infectious Disease
      Society of America CAP guidelines in 2003. AIM: The purpose of this review was to
      examine the current clinical evidence to support one option or the other by
      gathering all of the available published literature. We will review the existing
      controversies in terms of microbiology, immunology, and clinical outcomes
      comparing dual therapy (ie, with any combination of beta-lactams, macrolides, or
      fluoroquinolones) with monotherapy in the treatment of CAP. RESULTS: For the vast
      majority of patients with CAP (ie, outpatients and inpatients on medical wards),
      the type of antibiotic regimen prescribed does not have any significant impact.
      For patients with severe pneumonia, for which there is no accepted definition so
      far, the controversy remains alive. Mortality from pneumococcal pneumonia has
      been reduced over the last decades, but despite improved medical care, bacteremic
      pneumococcal pneumonia is still as lethal as ever, probably because of the aging
      population, the greater number of immunocompromised patients, and the number of
      patients with frequent comorbid conditions. Worldwide, the increasing rates of
      resistance of Streptococcus pneumoniae to antibiotics are also a serious concern,
      and the clinical implications are not always obvious. Although limited in number,
      the four studies showing the importance of adding a macrolide to a beta-lactam
      regimen for the treatment of bacteremic S pneumoniae pneumonia are retrospective
      and nonblinded, the findings are consistent, and they point to a trend that has
      to be explored more thoroughly. Studies published in the last few years suggest
      that combination therapy may be superior for bacteremic S pneumoniae pneumonia.
      CONCLUSION: In the meantime, for practical purposes, patients hospitalized with a
      diagnosis of severe CAP may benefit from a dual antibiotic therapy combining a
      third-generation cephalosporin and a macrolide. For the majority of hospitalized
      patients with CAP who are not severely ill, fluoroquinolone monotherapy remains
      an approved, tested, and reliable option. Indeed, the time for more aggressive
      outpatient fluoroquinolone therapy may reduce the number of patients who are
      hospitalized with CAP. Independent prospective studies comparing combination
      therapy with standard monotherapy are urgently required for hospitalized patients
      with severe CAP.

PMID- 16100191
TI  - Chemotherapy for elderly patients with non-small cell lung cancer: a review of
      the evidence.
AB  - Chemotherapy for elderly patients with non-small cell lung cancer (NSCLC) has
      been questioned due to the perceived potential for higher toxicity in this
      population, possibly attributable to progressive organ failure and comorbidities.
      This non-systematic review presents the authors' selection of key evidence for
      the use of chemotherapy for elderly patients with NSCLC. To date, single-agent
      chemotherapy with agents such as vinorelbine, gemcitabine, docetaxel, and
      paclitaxel has been a reasonable option. Data on non-platinum-based combinations
      are limited, but recent investigations of gemcitabine plus vinorelbine failed to
      show superiority over either agent alone. Retrospective subset analyses from
      large randomized trials suggest that the efficacy and tolerability of platinum
      based combination chemotherapy are similar in both the elderly and their younger
      counterparts. Further phase III trials that specifically examine platinum-based
      combinations in selected elderly NSCLC patients are therefore warranted. The
      potential impact of new targeted therapies-alone or in combination with
      chemotherapy-is being investigated.

PMID- 16100192
TI  - Emerging strategies in the prevention of venous thromboembolism in hospitalized
      medical patients.
AB  - Venous thromboembolism (VTE) remains a significant cause of morbidity and
      mortality in hospitalized patients with acute medical illness. The high
      prevalence of VTE in this patient population, its clinically silent nature, and
      associated morbidity and mortality indicate that prophylactic therapy is
      appropriate in those determined to be at increased risk. Unfractionated heparin
      (UFH) and low-molecular-weight heparin (LMWH) have been shown to reduce the
      incidence of VTE and are the primary therapies used for prophylaxis in these
      patients. Although both UFH and LMWH have received grade 1A recommendations for
      the prevention of VTE in at-risk medical patients in the 2004 American College of
      Chest Physicians consensus conference statements, LMWH has advantages over UFH in
      its once-daily dosing scheme, reduced incidence of major and minor bleeding
      events, and reduced incidence of heparin-induced thrombocytopenia. Fondaparinux
      is a novel antithrombotic agent characterized by specificity for factor Xa and a
      lack of platelet interaction. A recent clinical trial in hospitalized patients
      with acute medical illness found that fondaparinux significantly reduced the
      incidence of both VTE and fatal pulmonary embolism compared with placebo, without
      increased major bleeding. Despite the availability of effective
      thromboprophylactic therapies, VTE prophylaxis continues to be underutilized in
      hospitalized medical patients.

PMID- 16100193
TI  - Interatrial block: pandemic prevalence, significance, and diagnosis.

PMID- 16100194
TI  - Are physicians aware of the side effects of angiotensin-converting enzyme
      inhibitors?: a questionnaire survey in different medical categories.
AB  - STUDY OBJECTIVE: Angiotensin-converting enzyme inhibitors (ACE-I) are considered
      safe, but they are associated with characteristic side effects, namely cough and
      angioedema, usually requiring discontinuation. We perceived that referrals for
      these side effects have become more and more frequent; therefore, we evaluated
      the degree of knowledge on the safety of ACE-I in different medical categories.
      DESIGN: A questionnaire (13 questions) on side effects of ACE-I was posted to
      physicians. SETTING: Everyday clinical practice. PARTICIPANTS: Cardiologists,
      allergists, and general practitioners (GPs) from the National Healthcare System.
      MEASUREMENT AND RESULTS: Three hundred twelve physicians were contacted, and 154
      returned questionnaires that could be analyzed. Of the 154 physicians (mean age,
      45 years) 48 were cardiologists, 52 were GPs, and 54 were allergists. The
      percentage of correct answers was low: 31.9% for cardiologists, 40% for GPs, and
      33% for allergists. Thus, GPs provided a significantly higher percentage of
      correct answers with respect to the remaining categories (p = 0.05). The lower
      rate of correct answers (0 to 15.9%) concerned the time of onset of cough and the
      action to take. Cardiologists seemed to be less aware of the fact that
      angiotensin receptor blockers (sartans) can cross-react with ACE-I. CONCLUSION:
      Overall, there was a poor knowledge of the side effects of ACE-I. This may
      account for the increased referrals for chronic cough and angioedema.

PMID- 16100195
TI  - Optimization of the conditions for preservation of induced sputum: influence of
      freezing on cellular analysis.
AB  - BACKGROUND: Induced sputum (IS) analysis is a noninvasive, valid, and
      reproducible method for evaluating airway inflammation. It has been suggested
      that freezing of IS samples in order to delay analysis is feasible. However, the
      optimal conditions for preservation of IS samples have not been determined.
      OBJECTIVES: To determine optimal freezing conditions of IS samples, ensuring
      adequate specimen quality for assessment of cell viability, total cell count, and
      differential cell count. SUBJECTS AND METHODS: Twenty-one subjects were enrolled:
      6 healthy control subjects, 5 patients with allergic rhinitis, 5 patients with
      mild asthma, and 5 patients with severe asthma. Each came to the laboratory once
      for IS sampling. Cell plugs were homogenized with dithiothreitol and separated
      into 12 aliquots. Viability and total and differential cell counts were
      determined for each aliquot. Bovine serum albumin (BSA) with dimethylsulfoxide
      (DMSO) was added to half of the aliquots, and fetal bovine serum (FBS) with DMSO
      was added to the other half. One half of the aliquots containing BSA or FBS were
      frozen at -20 degrees C, and the other half were frozen at - 80 degrees C. After
      3, 7, or 10 days, samples were thawed and total cell counts, viability, and
      differential cell counts were assessed. RESULTS: Slide quality and total cell
      counts did not vary significantly according to freezing duration, temperature, or
      medium when compared to nonfrozen control samples. With FBS at -80 degrees C,
      cell viability did not vary significantly between control samples and freezing
      for 3, 7, and 10 days (59% vs 54%, 59% vs 54%, and 58% vs 54%, respectively; p >
      0.05), whereas every other condition showed a significant decrease. Freezing did
      not affect the eosinophil percentage significantly. CONCLUSION: Freezing of IS
      samples in FBS with DMSO at - 80 degrees C allows adequate preservation of IS
      specimens. Samples can be kept for at least 10 days in those conditions without
      significantly altering total cell counts, viability, and eosinophil percentage.

PMID- 16100196
TI  - Reaction patterns of the tracheobronchial wall to implanted noncovered metal
      stents.
AB  - BACKGROUND: Endoluminal implantation of stents has evolved as a nonsurgical
      treatment option for stenosis of the central airways. Based on the favorable
      results in treatment of tumorous tracheobronchial stenosis, stenting has been
      introduced into the therapy of nonmalignant stenosis. AIM: To study the long-term
      biocompatibility and incorporation of implanted bronchial stents based on the
      pathoanatomic reaction of the tracheobronchial system in humans. The
      incorporation of bronchial stents was documented, with specific interest in
      transformation or induction of dysplasia in the implantation zone. METHODS: The
      tracheobronchial reaction was studied in 18 patients 2 days to 18 months after
      implantation of 24 noncovered metal stents (Wallstent; Schneider; Bulach,
      Switzerland; n = 8; and Ultraflex; Boston Scientific; Natick, MA; n = 16).
      RESULTS: Stenting produced slow papillomatous growth of granulative tissue
      through the interfilamentary space of the stents. A nonspecific inflammatory
      response of nontumorous tissue could be documented. Sparse spots of superficial
      squamous cells occurred. No epithelial dysplasia or giant cells were detected
      within the stented region. The number of superficial ciliated cells in the
      implantation zone was markedly reduced. CONCLUSION: After stent insertion in the
      upper airways, no malignant transformation of initially nontumorous tissue
      occurs. Stenting seems to be a safe therapy option when considered even for
      nonmalignant airway stenoses.

PMID- 16100197
TI  - Induced sputum evaluation in microwave popcorn production workers.
AB  - OBJECTIVE: Severe airways obstruction and bronchiolitis obliterans have been
      reported in microwave popcorn production workers and attributed to inhalation of
      flavoring agents. We investigated whether exposure to flavoring agents is
      associated with airways inflammation in popcorn production workers. METHODS:
      Fifty-nine workers with high exposures and 22 patients with low exposures to
      flavoring vapors completed a questionnaire, spirometry, and sputum induction.
      Sputum cell counts were categorized as "high" if greater than (and "low" if less
      than or equal to) the median cell counts of a healthy external control group (n =
      24). We compared high- and low-exposure groups as well as all workers with
      control subjects. RESULTS: Neutrophil concentrations in nonsmoking workers were
      significantly higher than those of the healthy nonsmoking control group (p <
      0.05). The smoking-adjusted odds ratio for high neutrophil count (> 1.63 x
      10(5)/mL) was 3.8 (95% confidence interval, 1.3 to 11.5) in the high-exposure
      group compared with the low-exposure group. Sputum interleukin-8 and eosinophil
      cationic protein levels were higher in high-exposure workers than in low-exposure
      workers (p < 0.05). For the worker group, mean values of FEV1 percentage of
      predicted and FEV1/FVC percentage of predicted were > 95%. There were no
      relationships between sputum characteristics and the presence of airways
      obstruction. CONCLUSIONS: High exposure to popcorn flavoring agents is associated
      with neutrophilic airway inflammation in popcorn production workers. These data
      provide further evidence that popcorn production workers face a significant
      occupational hazard through exposure to flavoring agents.

PMID- 16100198
TI  - A mystery featuring right-to-left shunting despite normal intracardiac pressure.
AB  - The cause of right-to-left atrial shunting despite normal intracardiac pressures
      and normal or near-normal pulmonary function through a patent foramen ovale has
      still not been completely clarified. It is probably responsible for several
      linked diseases, such as paradoxical embolism, platypnea-orthodeoxia syndrome,
      migraine with aura, transient global amnesia, and decompression sickness in sport
      divers. Despite modern diagnostic methods, the underlying anatomophysiologic and
      pathogenic mechanisms of right-to-left atrial shunting without abnormal
      intracardiac pressures remain a matter of debate and controversy. Holistically
      speaking, a return to a direct study of embryology, gross anatomy, and physiology
      may help us elucidate the real mechanism of this paradoxical shunting.

PMID- 16100199
TI  - Plasma B-type natriuretic peptide in patients with pleural effusions: preliminary
      observations.
AB  - STUDY OBJECTIVES: To address the value of plasma B-type natriuretic peptide (BNP)
      concentrations as a diagnostic tool for determining the cardiac etiology of
      pleural effusions, and to determine possible differences of plasma BNP
      concentrations before and after pleurocentesis in patients with congestive heart
      failure (CHF). DESIGN: Observational study. SETTING: Tertiary care hospital.
      PATIENTS: Consecutive series of 64 patients with indications for diagnostic
      pleurocentesis. The final diagnosis of the underlying disease was assessed by
      clinical criteria. Seven patients were excluded due to pleural effusions of
      equivocal origin or due to obvious hemothorax secondary to trauma. INTERVENTION:
      Pleurocentesis attempting to drain effusions dry. Plasma BNP concentrations were
      measured directly before pleurocentesis and 24 h after the intervention. During
      these 24 h, the dosages of patients' medications were held constant. MEASUREMENTS
      AND RESULTS: In distinguishing between patients with pleural effusions caused by
      CHF (n = 31) and patients with pleural effusions attributable to other causes (n
      = 26), the area under the curve was 0.974 (SE, 0.021; 95% confidence interval,
      0.892 to 0.997) for plasma BNP. A BNP cutoff concentration of 2,201 ng/L had a
      sensitivity of 77% and a specificity of 100% in the diagnosis of CHF. The median
      plasma BNP concentrations in patients with pleural effusions caused by CHF (n =
      31) did not change within 24 h after pleurocentesis compared with the
      concentrations obtained before the procedure (before pleurocentesis, 3,227 ng/L;
      24 h after pleurocentesis, 2,759 ng/L; p = 0.189), despite a median removal of
      1,100 mL pleural fluid. CONCLUSIONS: Plasma BNP concentrations of patients with
      pleural effusions of unknown origin may be an aid in the diagnosis of CHF as the
      underlying cause. If plasma BNP is used as a surrogate marker of global cardiac
      function, there is no indication of hemodynamic improvement caused by
      pleurocentesis alone in patients with CHF and pleural effusions.

PMID- 16100200
TI  - Does delayed correction interfere with pulmonary functions and exercise tolerance
      in patients with tetralogy of fallot?
AB  - STUDY OBJECTIVES: To assess exercise tolerance and determine the distinct role of
      cardiac, respiratory, or peripheral factors on it after delayed surgical repair
      in patients with tetralogy of Fallot. DESIGN: The aerobic exercise capacity of 15
      adult patients (mean [+/- SD] age, 21 +/- 6; age range, 9 to 30 years) undergoing
      successful total correction at a mean age of 12 +/- 5 years (patients) was
      compared to healthy, matched control subjects by using right ventricle
      echocardiography, resting spirometry, and cardiopulmonary exercise tests at a
      mean postoperative time of 7.5 +/- 4.6 years. SETTING: Tertiary care referral
      centers. PATIENTS: Fifteen adult patients (mean age, 21 +/- 6 years; age range, 9
      to 30 years) undergoing successful total correction at a mean age of 12 +/- 5
      (patients) and 15 healthy, matched volunteers (control subjects). RESULTS: There
      was evidence for a slight right ventricular diastolic dysfunction in the
      patients. Mean FVC (88 +/- 9% vs 109 +/- 12% predicted, respectively) and FEV1
      (89 +/- 9% vs 109 +/- 12% predicted, respectively), although being within the
      normal range, were also decreased in comparison to those of control subjects (p <
      0.0001). Maximal oxygen consumption (V(O2max) decreased in both groups (55 +/-
      16% vs 61 +/- 23% predicted, respectively; p = 0.5); however, there were more
      individuals with severely decreased values among the patients (p = 0.05). V(O2)
      at the anaerobic threshold was also decreased in patients (33 +/- 15% vs 51 +/-
      8% predicted, respectively; p = 0.004). The maximum tolerable exercise time was
      17.3 +/- 4.5 min in patients vs 21.2 +/- 6.4 min in control subjects (p = 0.06).
      CONCLUSIONS: The exercise capacity after delayed repair was good in general
      compared to matched control subjects; however, exercise capacity may be slightly
      limited by ventilatory dysfunction, low anaerobic threshold, and lack of physical
      fitness despite New York Heart Association class improvement after undergoing the
      operation.

PMID- 16100201
TI  - A 73-year-old woman with a cough.

PMID- 16100202
TI  - Hemoptysis in a 77-year-old male with a systolic murmur.

PMID- 16100203
TI  - A 50-year-old woman with bilateral vocal cord paralysis and hilar mass.

PMID- 16100204
TI  - A 45-year-old man with left lung hypoperfusion and possible pulmonary embolism.

PMID- 16100205
TI  - Advance directives for truth disclosure.
AB  - INTRODUCTION: Although most patients wish to be fully informed about bad news
      such as a diagnosis of cancer, a significant minority prefer no or minimal
      information. We examined the value of asking patients about their disclosure
      preferences at the outset of hospitalization. METHODS: Consecutive patients
      admitted to a respiratory and a geriatric unit were asked whether and how they
      would wish to be told of cancer or Alzheimer disease. RESULTS: Of the 207
      patients interviewed, 174 (84%) wanted to be told about cancer or dementia; the
      proportion who would wish to be told did not differ between older patients (89 of
      108 patients; 82%) and younger patients (85 of 99 patients; 86%; p = 0.34).
      Thirty patients (15%) sought reassurance during or after the interview, and 13
      patients (6%) reported that they had been bothered by the questions. Of the 207
      patients, cancer or dementia was diagnosed in 23 patients (11%). Preferences for
      disclosure or nondisclosure were honored for 20 patients (87%). CONCLUSIONS:
      Seeking preferences regarding truth disclosure at the outset of hospitalization
      is helpful and feasible in everyday practice, and the results can be used by
      clinicians to improve communication with patients and families in accordance with
      patients' own wishes.

PMID- 16100206
TI  - Salvage of infected prosthetic grafts of the great vessels via muscle flap
      reconstruction.
AB  - OBJECTIVE: The infection of an aortic prosthetic graft presents a difficult
      challenge for surgeons. Conservative treatments such as debridement and
      antibiotic irrigation routinely fail, and patient survival rates are low.
      Literature has indicated that flap procedures often provide better treatment. In
      the present article, we report our experience utilizing pectoralis major muscle
      flaps, occasionally coupled with latissimus dorsi, rectus abdominis, and/or
      serratus anterior flaps, to wrap infected grafts and fill dead space. PATIENTS:
      Between 1990 and 2004, 10 patients were brought to our attention with infections
      of prosthetic grafts of the great vessels (7 men and 3 women; mean age, 53
      years). Infections in nine patients involved an ascending aortic graft, while one
      patient had an infected pulmonary artery graft. DESIGN: Following diagnosis and
      exploration, an initial debridement is performed, followed by 48 h of antibiotic
      irrigation. A definitive muscle flap procedure is then utilized to fill dead
      space and clear the infection, followed by an appropriate antibiotic regimen.
      RESULTS: The infections in all 10 patients were cleared using the muscle flap
      procedure. Two patients required a tapered-dose regimen of oral steroids, one of
      whom also required a secondary flap procedure due to the advanced stage of
      infection. Two other patients later died due to unrelated complications; however,
      autopsies revealed that operative sites had healed successfully. Patients were
      followed up for a period of 2 months to 2 years, and recurrence was not found.
      CONCLUSIONS: Our outcomes suggest that muscle flap procedures, specifically
      utilizing the pectoralis major and regional muscles, should be kept in mind in
      the management of life-threatening infections of aortic grafts. Due to the
      limited number of patients in this study, we feel more research with a larger
      volume of cases is warranted.

PMID- 16100207
TI  - Failure of gated single photon emission computer tomography scan to detect
      imminent acute plaque rupture causing acute ST-elevation myocardial infarction:
      case report.
AB  - The negative predictive value of a gated single photon emission computer
      tomography (SPECT) scan is very high, with an event rate of < 1% in the first
      year. However, the presence of nonobstructive coronary artery plaque should yield
      normal SPECT scan findings. On the other hand, most plaque ruptures, which are a
      major cause of acute myocardial infarction, occur in nonobstructive coronary
      artery plaque. Therefore, the findings of a gated SPECT scan should be normal if
      a ruptured plaque has not created significant obstruction despite the imminent
      threat of coronary artery occlusion. We present the first case report of a
      documented gated SPECT scan in a patient who had experienced an acute anterior Q
      wave myocardial infarction showing no significant ischemia in the anterior wall
      in the last minute of data acquisition.

PMID- 16100208
TI  - A case of sudden cardiac death due to isolated eosinophilic coronary arteritis.
AB  - Spontaneous coronary artery dissection is a very rare event and occurs most often
      in young women following childbirth. It is also known as a rare focal
      complication in Churg-Strauss syndrome. Here, we present the case of a 43-year
      old woman who died after spontaneous dissection of all three coronary arteries.
      The microscopic examination of coronary vessels showed severe eosinophilic
      infiltrations, whereas all extracardiac (medium-vessel and large-vessel) arteries
      were intact and free of inflammatory cells. Her history did not reveal allergy,
      asthma, or eosinophilia. To the best of our knowledge, this is the first case of
      spontaneous coronary dissection involving all coronary arteries without a history
      of Churg-Strauss syndrome or hypereosinophilic syndrome.

PMID- 16100209
TI  - Expiratory flow limitation is associated with orthopnea and reversed by
      vasodilators and diuretics in left heart failure.
AB  - BACKGROUND: In patients with acute left heart failure (LHF), orthopnea has also
      been related to the occurrence or worsening of expiratory flow limitation (EFL)
      in the supine position. We wished to assess whether short-term treatment with
      vasodilators and diuretics was able to abolish supine EFL and whether this could
      help to control orthopnea in patients with acute LHF. METHODS: In nine nonobese
      (ie, mean [+/- SD] body mass index, 24 +/- 5 kg/m2), never-smoker patients (two
      men and seven women; mean age, 77 +/- 7 years) with acute LHF (mean ejection
      fraction, 43 +/- 15%), we assessed EFL by the negative expiratory pressure method
      and dyspnea by the Borg scale, with patients in both the seated and supine
      positions, before and after short-term treatment with vasodilators and diuretics
      until hospital discharge. Orthopnea was defined as a positive difference in the
      Borg score between measurements made with the patient in the supine and seated
      positions. Postural variations in the end-expiratory lung volume were inferred
      from changes in inspiratory capacity (IC) that were measured under the same
      circumstances. RESULTS: Before treatment, with the patient in the seated position
      the mean dyspnea score was 1.5 +/- 0.5, the mean IC was 1.49 +/- 0.38 L, seven
      patients were non-flow-limited, and two patients were flow-limited. During
      recumbency, the mean dyspnea score was 2.7 +/- 0.5 (p < 0.01 vs seated position
      values), the mean IC was 1.66 +/- 0.45 L, and seven patients exhibited EFL. After
      a mean duration of 17 +/- 8 days of treatment (range, 7 to 28 days), EFL was
      detected in two patients only in the supine position, IC increased both in the
      seated position (1.65 +/- 0.34 L; p < 0.01) and the supine position (1.81 +/-
      0.41 L; p = 0.07) position, and, although only two patients denied orthopnea, the
      mean dyspnea score during recumbency actually decreased to 1.9 +/- 1.0 (p <
      0.05). CONCLUSIONS: Our results indicate that short-term treatment with
      vasodilators and diuretics is able to control orthopnea and to remove supine EFL
      in most patients with acute LHF, suggesting a posture-related increase in
      bronchial obstruction as the main mechanism of EFL, which appears to play a role
      in the occurrence and severity of orthopnea in these circumstances.

PMID- 16100210
TI  - Obstructing tracheal pulmonary Langerhans cell histiocytosis.
AB  - Pulmonary Langerhans cell histiocytosis, also known as eosinophilic granuloma, is
      an uncommon interstitial lung disease. A solitary nodule, usually parenchymal,
      may rarely be the only manifestation of the disease. We describe a case of
      Langerhans cell histiocytosis presenting as an obstructing tracheal lesion in a
      55-year-old woman. Following complete resection of the lesion via flexible
      bronchoscopy, full recovery was achieved. This case represents a unique cause for
      tracheal obstruction, as well as an unreported manifestation of pulmonary
      Langerhans cell histiocytosis.

PMID- 16100211
TI  - Continuous murmur caused by a ventricular septal defect post-myocardial
      infarction: visual display with a handheld computer.
AB  - Ventricular septal defects do not typically result in a continuous murmur. The
      only previously reported case involved a congenital ventricular septal defect. We
      report a case of an acquired ventricular septal defect following a large anterior
      myocardial infarction resulting in a continuous murmur. The continUous nature was
      confirmed both with 2D echocardiography and a specially equipped stethoscope in
      conjunction with a handheld computer to provide a visual display of the murmur. A
      proposed mechanism for the continuous murmur was discussed.

PMID- 16100212
TI  - Myocardial apoptotic index based on in situ DNA nick end-labeling of
      endomyocardial biopsies does not predict prognosis of dilated cardiomyopathy.
AB  - BACKGROUND: DNA breaks detected largely by terminal deoxynucleotidyltransferase
      mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) are observed
      in the hearts of patients with diseases such as dilated cardiomyopathy (DCM).
      STUDY OBJECTIVES: To determine the prognostic value of TUNEL assays in cases of
      DCM. DESIGN, SETTING, AND PARTICIPANTS: DCM patients were selected from among
      patients who had undergone left ventricular (LV) biopsy during the period from
      1994 to 2001 in our hospital. Of those, 46 (35 men and 11 women; mean [+/- SD]
      age, 58 +/- 11 years) who were followed up for > 3 years after the undergoing the
      biopsy (mean follow-up period, 4.9 +/- 2.0 years) or died during the follow-up
      period were entered into the present study. The myocardial apoptotic index was
      assessed in deparaffinized biopsy specimens that were stained using a
      conventional TUNEL assay. In addition, all surviving patients received a follow
      up echocardiographic examination. RESULTS: Ten of the 46 biopsy specimens (22%)
      contained TUNEL-positive myocytes; their mean apoptotic index was 0.44 +/- 1.05%.
      The apoptotic index showed no relation to cardiac functional parameters
      determined at the time of biopsy, however. Seven patients died during the follow
      up period, and 19 of the surviving patients were readmitted to the hospital
      because of a worsening of their heart failure. There was no significant
      difference in the apoptotic indexes of biopsy specimens from the dead and
      surviving patients, or between the surviving patients who were readmitted to the
      hospital and those who were not. There was also no significant correlation
      between the apoptotic index and changes in the LV ejection fraction, LV end
      diastolic diameter, or LV posterior wall thickness during follow-up. CONCLUSION:
      The apoptotic index derived from TUNEL assays is not predictive of the prognosis
      of patients with DCM-induced heart failure.

PMID- 16100213
TI  - Etanercept for refractory ocular sarcoidosis: results of a double-blind
      randomized trial.
AB  - PURPOSES: Study a tumor necrosis factor receptor antagonist (etanercept) in the
      treatment of chronic ocular sarcoidosis. SUBJECTS AND METHODS: Eighteen patients
      with ocular sarcoidosis and ongoing inflammation in the eyes. All patients had
      received at least 6 months of therapy with methotrexate and were currently
      receiving corticosteroids. Patients were randomized to receive either etanercept,
      25 mg subcutaneously twice a week, or placebo in a double-blind randomized trial.
      Treatment for ocular inflammation with systemic and local corticosteroids at the
      beginning and end of 6 months of treatment was noted. All patients underwent an
      ocular examination at the beginning and the end of the study by one
      ophthalmologist who was unaware of what treatment the patient was receiving.
      RESULTS: Three of the patients treated with etanercept and one treated with
      placebo were being treated with lower doses of corticosteroids by the end of the
      study. However, three of the etanercept patients and one of the placebo patients
      required larger doses of corticosteroids by the end of the study. The
      ophthalmology global assessment improved for two of the etanercept-treated
      patients and three of the placebo-treated patients. CONCLUSION: For most
      patients, therapy with etanercept was not associated with a significant
      improvement in their chronic ocular disease.

PMID- 16100214
TI  - Malignant pleural mesothelioma with less-frequent features.

PMID- 16100215
TI  - Patterns of melanoma antigen-A expression in lung cancer patients.

PMID- 16100216
TI  - Protease-antiprotease imbalance in inflammatory diseases in the lung.

PMID- 16100217
TI  - Pneumothorax following transthoracic fine-needle aspiration of the lung.

PMID- 16100218
TI  - Interleukin-1beta gene polymorphisms associated with COPD.

PMID- 16100219
TI  - Central or mixed venous oxygen saturation?

PMID- 16100220
TI  - Air pollution and pulmonary diseases.

PMID- 16100221
TI  - Publication of ethically suspect research: should it occur?

PMID- 16100222
TI  - Development and validation of an in-patient satisfaction questionnaire.
AB  - OBJECTIVE: To develop a psychometrically sound, hospital patient satisfaction
      questionnaire to be administered to patients discharged from medical and surgical
      services. DESIGN: Cross-sectional survey in Spanish. SETTING: Four acute care
      general hospitals of the Basque Health Service. STUDY PARTICIPANTS: Random
      samples of 650 discharged patients from each hospital during February and March
      2002. A total of 1910 patients responded to the questionnaire (73.5%). MAIN
      OUTCOME MEASURES: Overall perceived quality of health care and perceived health
      improvement. RESULTS: No sociodemographic differences were found between
      respondents and non-respondents. Six dimensions were identified from the factor
      analysis, explaining 50% of the variance. All items, except two, revealed
      loadings above 0.4. Cronbach's alpha exceeded 0.7 for all dimensions, except
      privacy. Comfort was the dimension with the lowest level of patient satisfaction,
      whereas privacy was the most satisfactory. The interscale correlations never
      exceeded the internal consistency of each scale. The analysis of the dimensions
      with two items of global assessment showed a positive correlation. CONCLUSIONS:
      The results obtained from the development and validation of the questionnaire
      provide evidence of its psychometric properties, although it would be useful to
      carry out further analyses to assess time-based properties of reliability. We
      found a positive relation between the degree of patient satisfaction and overall
      evaluation of the quality of health care, providing evidence of the ability of
      the questionnaire to correlate with other concepts. The in-patient satisfaction
      questionnaire could become a useful instrument in quality-of-care assessment.

PMID- 16100223
TI  - Imaging and quantifying carbohydrate transport to the developing ovaries of
      maize.
AB  - BACKGROUND AND AIMS: Shade or inadequate water can inhibit photosynthesis and
      limit the development of maize (Zea mays) ovaries around the time of pollination,
      potentially reducing the number of kernels at harvest. This study investigated
      whether the decreased photosynthesis diminished only the sugar supply or also
      altered the transport path to the ovaries. METHODS: Photosynthesis and water
      potentials (Psiw) were measured in the leaves while dry matter delivery was
      monitored in the ovaries. Ovary glucose, starch and acid invertase activities
      were measured in situ. Stems were fed xylem-mobile safranin or phloem-mobile
      carboxyfluorescein (CF), and the dye transport to the ovaries was determined. KEY
      RESULTS: Under normal conditions, the ovaries gained in dry mass, and starch
      accumulated in the pedicel and ovary wall. Glucose accumulated in the pedicel,
      apparently in the apoplast where insoluble (cell-wall-bound) acid invertase acted
      on the arriving sucrose. A glucose gradient developed from pedicel to nucellus.
      Safranin moved in the xylem and did not reach the ovary, but CF moved in the
      phloem and arrived at the ovary. CF also spread into the pedicel but unlike
      glucose it did not enter the nucellus. Low Psiw or shade decreased leaf
      photosynthesis, ovary dry mass accumulation, invertase activities, pedicel
      glucose, starch accumulation and CF delivery. Removal of these treatments
      reversed the effects. CONCLUSIONS: The success of CF in tracing the general path
      and rate of carbohydrate transport gave visual evidence that phloem transport to
      the ovary decreased at low Psiw or in the shade but otherwise remained
      functional. The decreases indicated that losses in carbohydrate delivery are
      central features of failed ovary development under these conditions. The
      selectivity of transport into the nucellus resembled the situation later when
      embryo and endosperm are present and selective uptake occurs from the apoplast.

PMID- 16100224
TI  - Polyploidy and cellular mechanisms changing leaf size: comparison of diploid and
      autotetraploid populations in two species of Lolium.
AB  - BACKGROUND AND AIMS: Growth and development of plant organs, including leaves,
      depend on cell division and expansion. Leaf size is increased by greater cell
      ploidy, but the mechanism of this effect is poorly understood. Therefore, in this
      study, the role of cell division and expansion in the increase of leaf size
      caused by polyploidy was examined by comparing various cell parameters of the
      mesophyll layer of developing leaves of diploid and autotetraploid cultivars of
      two grass species, Lolium perenne and L. multiflorum. METHODS: Three cultivars of
      each ploidy level of both species were grown under pot conditions in a controlled
      growth chamber, and leaf elongation rate and the cell length profile at the leaf
      base were measured on six plants in each cultivar. Cell parameters related to
      division and elongation activities were calculated by a kinematic method. KEY
      RESULTS: Tetraploid cultivars had faster leaf elongation rates than did diploid
      cultivars in both species, resulting in longer leaves, mainly due to their longer
      mature cells. Epidermal and mesophyll cells differed 20-fold in length, but were
      both greater in the tetraploid cultivars of both species. The increase in cell
      length of the tetraploid cultivars was caused by a faster cell elongation rate,
      not by a longer period of cell elongation. There were no significant differences
      between cell division parameters, such as cell production rate and cell cycle
      time, in the diploid and tetraploid cultivars. CONCLUSION: The results
      demonstrated clearly that polyploidy increases leaf size mainly by increasing the
      cell elongation rate, but not the duration of the period of elongation, and thus
      increases final cell size.

PMID- 16100225
TI  - A simple model for nitrogen-limited plant growth and nitrogen allocation.
AB  - BACKGROUND: and Aims In many studies of nitrogen-limited plant growth a linear
      relationship has been found between relative growth rate and plant nitrogen
      concentration, showing a negative intercept at a plant nitrogen concentration of
      zero. This relationship forms the basis of the nitrogen productivity theory. On
      the basis of empirical findings, several authors have suggested that there is
      also a distinctive relationship between allocation and plant nitrogen
      concentration. The primary aim of this paper is to develop a simple plant growth
      model that quantifies this relationship in mathematical terms. The model was
      focused on nitrogen allocation to avoid the complexity of differences in nitrogen
      concentrations in the different plant compartments. The secondary aim is to use
      the model for examining the processes that underlie the empirically based
      nitrogen productivity theory. METHODS: In the construction of the model we
      focused on the formation and degradation of biologically active nitrogen in
      enzymes involved in the photosynthetic process (photosynthetic nitrogen). It was
      assumed that, in nitrogen-limiting conditions, the formation of photosynthetic
      nitrogen is proportional to nitrogen uptake. Furthermore it was assumed that the
      degradation of photosynthetic nitrogen is governed by first-order kinetics. Model
      predictions of nitrogen allocation were compared with data from literature
      describing four studies of growth. Model predictions of whole plant growth were
      compared with the above-mentioned nitrogen productivity theory. KEY RESULTS:
      Allocation predictions agreed well with the investigated empirical data. The
      ratio of leaf nitrogen and plant nitrogen declines linearly with the inverse of
      plant nitrogen concentration. Nitrogen productivity is proportional to this
      ratio. Predictions for whole-plant growth were in accordance with the nitrogen
      productivity theory. CONCLUSIONS: The agreement between model predictions and
      empirical findings suggests that the derived equation for nitrogen allocation and
      its relationship to plant nitrogen concentration might be generally applicable.
      The negative intercept in the linear relationship between relative growth rate
      and plant nitrogen concentration is interpreted as being equal to the degradation
      constant of photosynthetic nitrogen.

PMID- 16100226
TI  - Variation in the activity of some enzymes of photorespiratory metabolism in C4
      grasses.
AB  - BACKGROUND AND AIMS: Photorespiration occurs in C4 plants, although rates are
      small compared with C3 plants. The amount of glycine decarboxylase in the bundle
      sheath (BS) varies among C4 grasses and is positively correlated with the granal
      index (ratio of the length of appressed thylakoid membranes to the total length
      of all thylakoid membranes) of the BS chloroplasts: C4 grasses with high granal
      index contained more glycine decarboxylase per unit leaf area than those with low
      granal index, probably reflecting the differences in O2 production from
      photosystem II and the potential photorespiratory capacity. Thus, it is
      hypothesized that the activities of peroxisomal enzymes involved in
      photorespiration are also correlated with the granal development. METHODS: The
      granal development in BS chloroplasts was investigated and activities of the
      photorespiratory enzymes assayed in 28 C4 grasses and seven C3 grasses. KEY
      RESULTS: The NADP-malic enzyme grasses were divided into two groups: one with low
      granal index and the other with relatively high granal index in the BS
      chloroplasts. Both the NAD-malic enzyme and phosphoenolpyruvate carboxykinase
      grasses had high granal index in the BS chloroplasts. No statistically
      significant differences were found in activity of hydroxypyruvate reductase
      between the C3 and C4 grasses, or between the C4 subtypes. The activity of
      glycolate oxidase and catalase were smaller in the C4 grasses than in the C3
      grasses. Among the C4 subtypes, glycolate oxidase activities were significantly
      smaller in the NADP-malic enzyme grasses with low granal index in the BS
      chloroplasts, compared with in the C4 grasses with substantial grana in the BS
      chloroplasts. CONCLUSIONS: There is interspecies variation in glycolate oxidase
      activity associated with the granal development in the BS chloroplasts and the O2
      production from photosystem II, which suggests different potential
      photorespiration capacities among C4 grasses.

PMID- 16100227
TI  - Nitrogen supply after removing the shoot apex increases the nicotine
      concentration and nitrogen content of tobacco plants.
AB  - BACKGROUND: and Aims High nicotine concentrations in leaves, especially in the
      upper leaves, offer a serious problem for the cultivation of tobacco (Nicotiana
      tabacum). Preliminary field experiments showed that rapid mineralization of soil
      N during late stages of growth may contribute to high nicotine concentrations in
      leaves. METHODS: A sand-culture experiment was carried out in the greenhouse. The
      N supply was controlled during the experiment, and different amounts of 15N were
      supplied during late stages of growth (after removal of the shoot apex), to
      investigate the contribution of the N taken up at this time to the N content of
      and nicotine concentration in tobacco plants. KEY RESULTS: Addition of 1.6 g or 4
      g 15N-labelled NH4NO3 after removing the shoot apex and flushing out the 14N did
      not increase leaf dry weights; however, it did result in delayed leaf senescence,
      more lateral bud formation, and an increase in 15N as a proportion of total N,
      and nicotine-15N as a proportion of total nicotine-N in each organ. The nicotine
      concentration, 15N and nicotine-15N abundances were increased from the bottom to
      the top leaves. When more 15N-labelled NH4NO3 was supplied, the nicotine
      concentration in leaves increased, and so did the 15N abundance in nicotine-N.
      CONCLUSION: Enhanced N supply in the later growth stages (after removing the
      apex) increased N content and nicotine concentration in tobacco plants. Nicotine
      was synthesized de novo during the late growth stages.

PMID- 16100228
TI  - An experimental evaluation of a group- versus computer-based intervention to
      improve food portion size estimation skills.
AB  - The ability to accurately estimate and measure food portion sizes is important
      for preventing and treating obesity. This study describes the development,
      implementation and evaluation of a group- versus computer-based intervention to
      improve food portion estimation abilities using real food and food models. A
      convenience sample of 76 women was randomly assigned to one of three conditions:
      computer training, group training or a waitlist control condition. Assessments at
      baseline and 2 weeks post-intervention included portion size testing using real
      foods and food models, self-efficacy for judging portion sizes and using
      measuring utensils, and knowledge of portion information. At baseline, greater
      estimation errors were observed for amorphous foods. No group by time interaction
      was observed on estimation of real foods; however, both the computer and group
      training resulted in significant improvements in estimating the size of food
      models, greater self-efficacy for judging portion sizes and more accurate
      knowledge of portion information compared with the control condition. Process
      measures indicated that the group training was deemed more helpful and more
      personally relevant to the participants.

PMID- 16100229
TI  - Expression of allene oxide cyclase and accumulation of jasmonates during
      organogenic nodule formation from hop (Humulus lupulus var. Nugget) internodes.
AB  - A crucial step in the biosynthesis of jasmonic acid (JA) is the formation of its
      stereoisomeric precursor, cis-(+)-12-oxophytodienoic acid (OPDA), which is
      catalyzed by allene oxide cyclase (AOC, EC 5.3.99.6). A cDNA of AOC was isolated
      from Humulus lupulus var. Nugget. The ORF of 765 bp encodes a 255 amino acid
      protein, which carries a putative chloroplast targeting sequence. The recombinant
      protein without its putative chloroplast target sequence showed significant AOC
      activity. Previously we demonstrated that wounding induces organogenic nodule
      formation in hop. Here we show that the AOC transcript level increases in
      response to wounding of internodes, peaking between 2 and 4 h after wounding. In
      addition, Western blot analysis showed elevated levels of AOC peaking 24 h after
      internode inoculation. The AOC increase was accompanied by increased JA levels 24
      h after wounding, whereas OPDA had already reached its highest level after 12 h.
      AOC is mostly present in the vascular bundles of inoculated internodes. During
      prenodule and nodule formation, AOC levels were still high. JA and OPDA levels
      decreased down to 10 and 118 pmol (g FW)(-1), respectively, during nodule
      formation, but increased during plantlet regeneration. Double immunolocalization
      analysis of AOC and Rubisco in connection with lugol staining showed that AOC is
      present in amyloplasts of prenodular cells and in the chloroplasts of vacuolated
      nodular cells, whereas meristematic cells accumulated little AOC. These data
      suggest a role of AOC and jasmonates in organogenic nodule formation and plantlet
      regeneration from these nodules.

PMID- 16100230
TI  - Response to darkness of late-responsive dark-inducible genes is positively
      regulated by leaf age and negatively regulated by calmodulin-antagonist-sensitive
      signalling in Arabidopsis thaliana.
AB  - Induction after prolonged darkness distinguishes the late-responsive genes din2
      and din9 from the early-responsive gene din3 in Arabidopsis. The former genes
      were coincidently induced with the senescence marker gene YLS4 in rosette leaves
      of different ages and in the early-senescence mutant hys1. The calmodulin
      antagonists W-7, trifluoperazine, and fluphenazine accelerated the expression of
      the former genes in darkness but not in light, and had little effect on the
      latter gene. Our results suggest that Ca(2+)/calmodulin signalling conveys a
      negative signal that suppresses the responses of late-responsive din genes to
      prolonged darkness. The results are discussed in relation to natural senescence.

PMID- 16100231
TI  - Troponins in prediction of cardiotoxic effects.

PMID- 16100233
TI  - High incidence of INR alteration in gastrointestinal cancer patients treated with
      mini-dose warfarin and 5-fluorouracil-based regimens.

PMID- 16100234
TI  - Pregnancy outcome of two patients treated with imatinib.

PMID- 16100235
TI  - Glucose, insulin and potassium applied as perioperative hyperinsulinaemic
      normoglycaemic clamp: effects on inflammatory response during coronary artery
      surgery.
AB  - BACKGROUND: The clinical benefits of glucose-insulin-potassium (GIK) and tight
      glycaemic control in patients undergoing coronary artery bypass grafting (CABG)
      may be partly explained by an anti-inflammatory effect. We applied GIK as a
      hyperinsulinaemic normoglycaemic clamp for >25 h and quantified its effect on
      systemic inflammation in patients undergoing CABG. METHODS: Data obtained in 21
      non-diabetic patients with normal left ventricular function scheduled for
      elective coronary artery surgery, who were randomly allocated to a control or GIK
      group, were analysed. In GIK patients, regular insulin was infused at a fixed
      rate of 0.1 IU kg(-1) h(-1). The infusion rate of glucose (30%) was adjusted to
      maintain blood glucose levels within a target range of 4.0-5.5 mmol litre(-1).
      Plasma concentrations of interleukins 6, 8 and 10, C-reactive protein (CRP) and
      serum amyloid A (SAA) were measured on the day of surgery and on the first and
      second postoperative days (POD1 and POD2). RESULTS: In the GIK group
      hypoglycaemia (glucose <2.2 mmol litre(-1)) did not occur, whereas hyperglycemia
      (glucose >6.1 mmol litre(-1)) developed in 15% of all measurements. In control
      patients, hyperglycaemia developed in >80% of all measurements in the presence of
      low endogenous insulin levels. CRP and SAA levels increased in both groups, with
      maximum levels measured on POD2. GIK treatment significantly reduced CRP and SAA
      levels. Interleukin levels increased significantly in both groups following
      cardiopulmonary bypass, but no differences were found between the groups.
      CONCLUSION: Hyperinsulinaemic normoglycaemic clamp is an effective method of
      maintaining tight glycaemic control in patients undergoing CABG and it attenuates
      the systemic inflammatory response in these patients. This effect may partly
      contribute to the reported beneficial effect of glycaemic control in patients
      undergoing CABG.

PMID- 16100236
TI  - Pharmacokinetics of levobupivacaine after caudal epidural administration in
      infants less than 3 months of age.
AB  - BACKGROUND: There are few data describing levobupivacaine pharmacokinetics in
      infants (<3 months) after caudal administration. METHODS: An open-label study was
      undertaken to examine the pharmacokinetics of levobupivacaine 2.5 mg ml(-1), 2 mg
      kg(-1) in children aged less than 3 months after single-shot caudal epidural
      administration. Plasma concentrations were determined at intervals from 0.5 to 4
      h after injection. A population pharmacokinetic analysis of levobupivacaine time
      concentration profiles (84 observations) from 22 infants with mean postnatal age
      (PNA) 2.0 (range 0.6-2.9) months was undertaken using non-linear mixed effects
      models (NONMEM). Time-concentration profiles were analysed using a one
      compartment model with first-order input and first-order elimination. Estimates
      were standardized to a 70 kg adult using allometric size models. RESULTS:
      Population parameter estimates (between-subject variability) for total
      levobupivacaine were clearance (CLt) 12.8 [coefficient of variation (CV) 50.6%]
      litre h(-1) 70 kg(-1), volume of distribution (Vt) 202 (CV 31.6%) litre 70 kg(
      1), absorption half-life (Tabs) 0.323 (CV 18.6%) h 70 kg(-1). Estimates for the
      unbound drug were clearance (CLfree) 104 (CV 43.5%) litre h(-1) 70 kg(-1), volume
      of distribution (Vfree) 1700 (CV 44.9%) litre 70 kg(-1), absorption half-life
      (Tabsfree) 0.175 (CV 83.7%) h 70 kg(-1). There was no effect attributable to PNA
      on CL or V. Time to peak plasma concentration (Tmax) was 0.82 (CV 18%) h. Peak
      plasma concentration (Cmax) was 0.69 (CV 25%) microg ml(-1) for total
      levobupivacaine and 0.09 (CV 37%) microg ml(-1) for unbound levobupivacaine.
      CONCLUSIONS: Clearance in infants is approximately half that described in adults,
      suggesting immaturity of P450 CYP3A4 and CYP1A2 enzyme isoforms that metabolize
      levobupivacaine in infants. This lower clearance delays Tmax, which was noted to
      occur approximately 50 min after administration of caudal epidural
      levobupivacaine.

PMID- 16100237
TI  - A comparison of the postoperative analgesic efficacy of single-dose epidural
      tramadol versus morphine in children.
AB  - BACKGROUND: The aim of this study was to compare epidural administration of
      single-dose tramadol with morphine in children undergoing urological surgery with
      respect to preoperative haemodynamic effects, postoperative analgesia and side
      effects. METHODS: Eighty children aged between 7 and 14 undergoing urological
      surgery were included in the study. After intubation, in the lateral decubitus
      position, a single dose of morphine 0.1 mg kg(-1) in isotonic saline 0.2 ml kg(
      1) (morphine group) and tramadol 2 mg kg(-1) in isotonic saline 0.2 ml kg(-1)
      (tramadol group) was administered epidurally. During the 24-h postoperative
      period, heart rate, systolic blood pressure, respiration rate, pain score and
      sedation level of the patients were monitored. A modified objective pain score of
      3 or lower was accepted as an indicator of inadequate analgesia and these
      patients were given 20 acetaminophen mg kg(-1) rectally or orally. Time to first
      analgesia was noted. Sedation level was evaluated with a four-point sedation
      scale. RESULTS: In the postoperative period, pain scores and the average time for
      analgesic requirement were similar in the two groups. However, the incidences of
      allergic rash, itching, sedation and respiratory depression and sedation score
      were greater in the morphine group than in the tramadol group. CONCLUSION:
      Greater epidural use of tramadol may be preferred to morphine for postoperative
      analgesia under these circumstances.

PMID- 16100238
TI  - Allergic reactions in anaesthesia: are suspected causes confirmed on subsequent
      testing?
AB  - BACKGROUND: The aim of this retrospective survey of possible allergic reactions
      during anaesthesia was to investigate whether the cause suspected by
      anaesthetists involved corresponded with the cause found on subsequent
      investigation in the Danish Anaesthesia Allergy Centre (DAAC). METHODS: Case
      notes and anaesthetic charts from 111 reactions in 107 patients investigated in
      the DAAC were scrutinized for either suspicions of or warnings against specific
      substances stated to be the cause of the supposed allergic reaction. RESULTS: In
      67 cases, one or more substances were suspected. In 49 of these (73%) the
      suspected cause did not match the results of subsequent investigation, either a
      different substance being the cause or no cause being found. Only five cases (7%)
      showed a complete match between suspected cause and investigation result. In the
      remaining 13 cases (19%) there was a partial match, the right substance being
      suspected, but investigations showed an additional allergen or several
      substances, including the right substance being suspected. CONCLUSIONS: An
      informed guess is not a reliable way of determining the cause of a supposed
      allergic reaction during anaesthesia and may put a significant number of patients
      at unnecessary risk. Some patients may be labelled with a wrong allergy, leading
      to unnecessary warnings against harmless substances, and some patients may be put
      at risk of subsequent re-exposure to the real allergen. Patients with suspected
      allergic reactions during anaesthesia should be referred for investigation in
      specialist centres whenever possible.

PMID- 16100239
TI  - Expression of the epidermal growth factor system in human endometrium during the
      menstrual cycle.
AB  - The epidermal growth factor (EGF) system is ubiquitous in humans and plays
      fundamental roles in embryogenesis, development, proliferation and
      differentiation. As the endometrium of fertile women is characterized by
      proliferation and differentiation, we hypothesize a role for the EGF system.
      Fourteen premenopausal women had endometrial samples removed on day 6 +/- 1 and
      day 6 +/- 1 and 12 +/- 1 after ovulation during one menstrual cycle. RNA was
      extracted and analysed by real-time PCR, and immunohistochemistry was performed
      to localize the components of the EGF system. Human EGF Receptor 1 (HER1) showed
      highest expression during the proliferative phase, HER2 and HER4 during the early
      and HER3 during the late secretory phase. Amphiregulin (AR) and transforming
      growth factor alpha (TGFalpha) expression is highest in proliferative phase.
      Heparin binding (HB)-EGF and betacellulin (BCL) show no variation. Epiregulin
      (EP) is detectable in some samples. EGF is undetectable. HER1, HER2, HER3 and
      HER4 were localized to the epithelium and glands HER3 and HER4 solely in the
      secretory phase. Amphiregulin was seen in leucocytes and stromal cells, TGFalpha
      and betacellulin in the epithelial lining, epiregulin in stromal cells whereas HB
      EGF and EGF are undetectable. In conclusions, we observed cyclical expression of
      the four EGF receptors and two ligands and localized all four receptors and four
      ligands in endometrial biopsies. This suggests a role for the EGF system in
      growth of the endometrium.

PMID- 16100240
TI  - Human FSH beta subunit gene is highly conserved.
AB  - FSH is a pituitary gonadotropin that along with LH plays a key role in the
      regulation of gonadal function. The gonadotropic hormones are composed of two
      subunits, the common alpha subunit and the hormone-specific beta subunit, which
      determines the binding to specific receptors and induction of biological
      response. Unlike the LHbeta gene, shown in earlier studies to harbour several
      amino acid-altering polymorphisms and mutations, information about the eventual
      sequence variation of the human FSHbeta subunit is not available. In this study,
      we made sequence analysis and comparison of polymorphisms found in FSHbeta in two
      Caucasian populations, the Finns and the Danes. It was found that FSHbeta subunit
      is highly conserved in these populations. Compared with the published sequences,
      only three silent polymorphisms were detected in the coding regions of the gene,
      and the promoter sequence was completely identical with the reported sequence.
      Two of the polymorphisms found were novel, one in the Finnish and one in the
      Danish population. The results of the sequence analysis show that the human
      FSHbeta gene is highly conserved and amino acid changing mutations are apparently
      extremely rare, at least in the samples collected randomly from control
      populations. This may be due to the crucial role of normal FSH function in the
      regulation of fertility.

PMID- 16100241
TI  - Examination of stimulation mechanism and strength-interval curve in cardiac
      tissue.
AB  - Understanding the basic mechanisms of excitability through the cardiac cycle is
      critical to both the development of new implantable cardiac stimulators and
      improvement of the pacing protocol. Although numerous works have examined
      excitability in different phases of the cardiac cycle, no systematic experimental
      research has been conducted to elucidate the correlation among the virtual
      electrode polarization pattern, stimulation mechanism, and excitability under
      unipolar cathodal and anodal stimulation. We used a high-resolution imaging
      system to study the spatial and temporal stimulation patterns in 20 Langendorff
      perfused rabbit hearts. The potential-sensitive dye di-4-ANEPPS was utilized to
      record the electrical activity using epifluorescence. We delivered S1-S2 unipolar
      point stimuli with durations of 2-20 ms. The anodal S-I curves displayed a more
      complex shape in comparison with the cathodal curves. The descent from
      refractoriness for anodal stimulation was extremely steep, and a local minimum
      was clearly observed. The subsequent ascending limb had either a dome-shaped
      maximum or was flattened, appearing as a plateau. The cathodal S-I curves were
      smoother, closer to a hyperbolic shape. The transition of the stimulation
      mechanism from break to make always coincided with the final descending phase of
      both anodal and cathodal S-I curves. The transition is attributed to the bidomain
      properties of cardiac tissue. The effective refractory period was longer when
      negative stimuli were delivered than for positive stimulation. Our spatial and
      temporal analyses of the stimulation patterns near refractoriness show always an
      excitation mechanism mediated by damped wave propagation after S2 termination.

PMID- 16100242
TI  - Effect of mutation of amino acids 246-251 (KRKHKK) in HSP72 on protein synthesis
      and recovery from hypoxic injury.
AB  - Heat shock protein (HSP)72, the inducible form of HSP70, protects cells against a
      variety of injuries, but underlying mechanisms are poorly defined. To investigate
      the protective effects of HSP72, multiple clones expressing wild-type (WT) HSP72
      and two mutants with defective nucleolar and nuclear localization (M45 and 985A,
      respectively) were made with the tet-off system in C2C12 cells. Four different
      parameters of cell function/injury were examined after simulated ischemia:
      protein synthesis, polysome formation, DNA synthesis, and lactate dehydrogenase
      (LDH release). Overexpression of WT HSP72 was also compared to nontransfected
      C2C12 cells. As expected, overexpression of HSP72 protected against simulated
      ischemia and reoxygenation for all parameters. In contrast, both M45 and 985A
      showed abnormal protein synthesis and polysome formation, both after simulated
      ischemia and under control conditions. Total RNA was slightly reduced in M45 and
      985A at baseline, but 1 h after hypoxia, RNA levels were protected in all clones
      but significantly decreased in nontransfected C2C12 cells. Clones expressing 985A
      had nuclear retention of mRNA, suggesting that HSP72 is needed for nuclear export
      of RNA. All clones, both WT and mutant, had protection of DNA synthesis compared
      to C2C12 cells, but 985A had greater release of LDH after injury than any other
      group. These results support a multifactoral protective effect of HSP72, some
      aspects dependent on nuclear localization with stress and some not. The
      protection of protein synthesis and polysome formation, and abnormalities in
      these with the mutants, support a role for HSP72 in these processes both in the
      normal cell and in injury.

PMID- 16100243
TI  - Stimulation of NTS A1 adenosine receptors evokes counteracting effects on
      hindlimb vasculature.
AB  - Our previous studies concluded that stimulation of the nucleus of the solitary
      tract (NTS) A2a receptors evokes preferential hindlimb vasodilation mainly via
      inducing increases in preganglionic sympathetic nerve activity (pre-ASNA)
      directed to the adrenal medulla. This increase in pre-ASNA causes the release of
      epinephrine and subsequent activation of beta-adrenergic receptors that are
      preferentially located in the skeletal muscle vasculature. Selective activation
      of NTS A1 adenosine receptors evokes variable, mostly pressor effects and
      increases pre-ASNA, as well as lumbar sympathetic activity, which is directed to
      the hindlimb. These counteracting factors may have opposite effects on the
      hindlimb vasculature resulting in mixed vascular responses. Therefore, in
      chloralose-urethane-anesthetized rats, we evaluated the contribution of
      vasodilator versus vasoconstrictor effects of stimulation of NTS A1 receptors on
      the hindlimb vasculature. We compared the changes in iliac vascular conductance
      evoked by microinejctions into the NTS of the selective A1 receptor agonist N6
      cyclopentyladenosine (330 pmol in 50 nl volume) in intact animals with the
      responses evoked after beta-adrenergic blockade, bilateral adrenalectomy,
      bilateral lumbar sympathectomy, and combined adrenalectomy + lumbar
      sympathectomy. In intact animals, stimulation of NTS A1 receptors evoked variable
      effects: increases and decreases in mean arterial pressure and iliac conductance
      with prevailing pressor and vasoconstrictor effects. Peripheral beta-adrenergic
      receptor blockade and bilateral adrenalectomy eliminated the depressor component
      of the responses, markedly potentiated iliac vasoconstriction, and tended to
      increase the pressor responses. Lumbar sympathectomy tended to decrease the
      pressor and vasoconstrictor responses. After bilateral adrenalectomy plus lumbar
      sympathectomy, a marked vasoconstriction in iliac vascular bed still persisted,
      suggesting that the vasoconstrictor component of the response to stimulation of
      NTS A1 receptors is mediated mostly via circulating factors (e.g., vasopressin,
      angiotensin II, or circulating catecholamines released from other sympathetic
      terminals). These data strongly suggest that stimulation of NTS A1 receptors
      exerts counteracting effects on the iliac vascular bed: activation of the adrenal
      medulla and beta-adrenergic vasodilation versus vasoconstriction mediated by
      neural and humoral factors.

PMID- 16100244
TI  - MCI-186 (edaravone), a novel free radical scavenger, protects against acute
      autoimmune myocarditis in rats.
AB  - In this study, we tested the hypothesis that MCI-186 (3-methyl-1-phenyl-2
      pyrazolin-5-one; edaravone), a novel free radical scavenger, protects against
      acute experimental autoimmune myocarditis (EAM) in rats by the radical scavenging
      action associated with the suppression of cytotoxic myocardial injury. Recent
      evidence suggests that oxidative stress may play a role in myocarditis. We
      administered MCI-186 intraperitoneally at 1, 3, and 10 mg.kg(-1).day(-1) to rats
      with EAM for 3 wk. The results were compared with untreated rats with EAM. MCI
      186 treatment did not affect hemodynamics. MCI-186 treatment (3 and 10 mg.kg(
      1).day(-1)) reduced the severity of myocarditis as assessed by comparing the
      heart-to-body weight ratio and pathological scores. Myocardial interleukin-1beta
      (IL-1beta)-positive cells and myocardial oxidative stress overload with DNA
      damage in rats with EAM given MCI-186 treatment were significantly less compared
      with those of the untreated rats with EAM. In addition, MCI-186 treatment
      decreased not only the myocardial protein carbonyl contents but also the
      myocardial thiobarbituric acid reactive substance products in rats with EAM. The
      formation of hydroxyl radicals in MCI-186-treated heart homogenates was decreased
      compared with untreated heart homogenates. Furthermore, cytotoxic activities of
      lymphocytes of rats with EAM treated with MCI-186 were significantly lower
      compared with those of the untreated rats with EAM. Hydroxyl radicals may be
      involved in the development of myocarditis. MCI-186 protects against acute EAM in
      rats associated with scavenging hydroxyl free radicals, resulting in the
      suppression of autoimmune-mediated myocardial damage associated with reduced
      oxidative stress state.

PMID- 16100245
TI  - Mechanical properties of the interaction between fibronectin and alpha5beta1
      integrin on vascular smooth muscle cells studied using atomic force microscopy.
AB  - The mechanical properties of integrin-extracellular matrix (ECM) interactions are
      important for the mechanotransduction of vascular smooth muscle cells (VSMC), a
      process that is associated with focal adhesions, and can be of particular
      significance in cardiovascular disease. In this study, we characterized the
      unbinding force and binding activity of the initial fibronectin (FN)-alpha5beta1
      interaction on the surface of VSMC using atomic force microscopy (AFM). It is
      postulated that these initial binding events are important to the subsequent
      focal adhesion assembly. FN-VSMC adhesions were selectively blocked by antibodies
      against alpha5- and beta1-integrins as well as RGD-containing peptides but not by
      antibodies against alpha4- and beta3-integrins, indicating that FN primarily
      bound to alpha5beta1. A characteristic unbinding force of 39 +/- 8 pN was
      observed and interpreted to represent the FN-alpha5beta1 single-bond strength.
      The ability of FN to adhere to VSMC (binding probability) was significantly
      reduced by integrin antagonists, serum starvation, and platelet-derived growth
      factor (PDGF)-BB, whereas lysophosphatidic acid (LPA) increased FN binding.
      However, no significant change in the resolved unbinding force was observed.
      After engagement, the force required to dislodge the FN-coated bead from VSMC
      increased with increasing of contact time, suggesting a time-dependent increase
      in number of adhesions and/or altered binding affinity. LPA enhanced this
      process, whereas PDGF reduced it, suggesting that these factors also affect the
      multimolecular process of focal contact assembly. Thus AFM is a powerful tool for
      the characterization of the mechanical properties of integrin-ECM interactions
      and their regulation. Our results indicate that the functional activity of
      alpha5beta1 and focal contact assembly can be rapidly regulated.

PMID- 16100246
TI  - Malonyl-CoA decarboxylase inhibition suppresses fatty acid oxidation and reduces
      lactate production during demand-induced ischemia.
AB  - The rate of cardiac fatty acid oxidation is regulated by the activity of
      carnitine palmitoyltransferase-I (CPT-I), which is inhibited by malonyl-CoA. We
      tested the hypothesis that the activity of the enzyme responsible for malonyl-CoA
      degradation, malonyl-CoA decarboxlyase (MCD), regulates myocardial malonyl-CoA
      content and the rate of fatty acid oxidation during demand-induced ischemia in
      vivo. The myocardial content of malonyl-CoA was increased in anesthetized pigs
      using a specific inhibitor of MCD (CBM-301106), which we hypothesized would
      result in inhibition of CPT-I, reduction in fatty acid oxidation, a reciprocal
      activation of glucose oxidation, and diminished lactate production during demand
      induced ischemia. Under normal-flow conditions, treatment with the MCD inhibitor
      significantly reduced oxidation of exogenous fatty acids by 82%, shifted the
      relationship between arterial fatty acids and fatty acid oxidation downward, and
      increased glucose oxidation by 50%. Ischemia was induced by a 20% flow reduction
      and beta-adrenergic stimulation, which resulted in myocardial lactate production.
      During ischemia MCD inhibition elevated malonyl-CoA content fourfold, reduced
      free fatty acid oxidation rate by 87%, and resulted in a 50% decrease in lactate
      production. Moreover, fatty acid oxidation during ischemia was inversely related
      to the tissue malonyl-CoA content (r = -0.63). There were no differences between
      groups in myocardial ATP content, the activity of pyruvate dehydrogenase, or
      myocardial contractile function during ischemia. Thus modulation of MCD activity
      is an effective means of regulating myocardial fatty acid oxidation under normal
      and ischemic conditions and reducing lactate production during demand-induced
      ischemia.

PMID- 16100247
TI  - Charge modification of the endothelial surface layer modulates the permeability
      barrier of isolated rat mesenteric small arteries.
AB  - We hypothesized that modulation of the effective charge density of the
      endothelial surface layer (ESL) results in altered arterial barrier properties to
      transport of anionic solutes. Rat mesenteric small arteries (diameter
      approximately 190 microm) were isolated, cannulated, perfused, and superfused
      with MOPS-buffered physiological salt solutions. MOPS-solutions were of normal
      ionic strength (162 mM, MOPS), low ionic strength (81 mM, LO-MOPS), or high ionic
      strength (323 mM, HI-MOPS), to modulate ESL charge density (normal, high, or low
      ESL charge, respectively). Osmolarity of MOPS, LO-MOPS, and HI-MOPS was kept
      constant at 297 mosmol/l, using additional glucose when necessary. Perfusate
      solutions were supplemented with 1% BSA. Arteries were cannulated with a double
      barreled theta-pipet on the inlet side and a regular pipet on the outlet side.
      After infusion of FITC-labeled dextran of 50 kDa (FITC-Delta50) and the
      endothelial membrane dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine
      perchlorate, the dynamics of arterial dye filling were determined with confocal
      microscopy. ESL thickness, as determined from the initial exclusion zone for FITC
      Delta50 on the luminal endothelial surface, was 6.3 +/- 1.4 microm for LO-MOPS,
      2.7 +/- 1.0 microm for MOPS, and 1.1 +/- 1.3 microm for HI-MOPS. At low ionic
      strength, FITC-Delta50 permeated into the ESL with a total ESL permeation time
      (tauESL) of 26 min, and at normal ionic strength with a tauESL of 20 min. No
      apparent exclusion of FITC-Delta50 from the ESL could be observed at high ionic
      strength. In conclusion, we demonstrate that the modulation of solvent ionic
      strength influences the thickness and barrier properties of the ESL.

PMID- 16100248
TI  - Sustained hypothermia accelerates microvascular thrombus formation in mice.
AB  - Cold is supposed to be associated with alterations in blood coagulation and a
      pronounced risk for thrombosis. We studied the effect of clinically encountered
      systemic hypothermia on microvascular thrombosis in vivo and in vitro. Ferric
      chloride-induced microvascular thrombus formation was analyzed in cremaster
      muscle preparations from hypothermic mice. Additionally, flow cytometry and
      Western blot analysis was used to evaluate the effect of hypothermia on platelet
      activation. To test whether preceding hypothermia predisposes for enhanced
      thrombosis, experiments were repeated after hypothermia and rewarming to 37
      degrees C. Control animals revealed complete occlusion of arterioles and venules
      after 742 +/- 150 and 824 +/- 172 s, respectively. Systemic hypothermia of 34
      degrees C accelerated thrombus formation in arterioles and venules (279 +/- 120
      and 376 +/- 121 s; P < 0.05 vs. 37 degrees C). This was further pronounced after
      cooling to 31 degrees C (163 +/- 57 and 281 +/- 71 s; P < 0.05 vs. 37 degrees C).
      Magnitude of thrombin receptor activating peptide (TRAP)-induced platelet
      activation increased with decreasing temperatures, as shown by 1.8- and 3.0-fold
      increases in mean fluorescence after PAC-1 binding to glycoprotein (GP)IIb-IIIa
      and 1.6- and 2.9-fold increases of fibrinogen binding on incubation at 34 degrees
      C and 31 degrees C. Additionally, tyrosine-specific protein phosphorylation in
      platelets was increased at hypothermic temperatures. In rewarmed animals,
      kinetics of thrombus formation were comparable to those in normothermic controls.
      Concomitantly, spontaneous and TRAP-enhanced GPIIb-IIIa activation did not differ
      between rewarmed platelets and those maintained continuously at 37 degrees C.
      Moderate systemic hypothermia accelerates microvascular thrombosis, which might
      be mediated by increased GPIIb-IIIa activation on platelets but does not cause
      predisposition with increased risk for microvascular thrombus formation after
      rewarming.

PMID- 16100249
TI  - Role of myofibrillogenesis regulator-1 in myocardial hypertrophy.
AB  - Myofibrillogenesis regulator-1 (MR-1) is a novel homologous gene, identified from
      a human skeletal muscle cDNA library, that interacts with contractile proteins
      and exists in human myocardial myofibrils. The present study investigated MR-1
      protein expression in hypertrophied myocardium and MR-1 involvement in cardiac
      hypertrophy. Cardiac hypertrophy was induced by abdominal aortic stenosis (AAS)
      in Sprague-Dawley rats. Left ventricular (LV) hypertrophy was assessed by the
      ratio of LV wet weight to whole heart weight (LV/HW) or LV weight to body weight
      (LV/BW). Rat MR-1 (rMR-1) expression in the myocardium was detected by
      immunohistochemical and Western blotting analysis. Hypertrophy was induced by ANG
      II incubation in cultured neonatal rat cardiomyocytes. The effect of rMR-1 RNA
      interference on ANG II-induced hypertrophy was studied by transfection of
      cardiomyocytes with an RNA interference plasmid, pSi-1, which targets rMR-1.
      Hypertrophy in cardiomyocytes was assessed by [3H]Leu incorporation and myocyte
      size. rMR-1 protein expression in cardiomyocytes was detected by Western
      blotting. We found that AAS resulted in a significant increase in LV/HW and
      LV/BW: 89% and 86%, respectively (P < 0.01). Immunohistochemistry and Western
      blot analysis demonstrated upregulated rMR-1 protein expression in hypertrophic
      myocardium. ANG II induced a 24% increase in [3H]Leu incorporation and a 65.8%
      increase in cell size compared with control cardiomyocytes (P < 0.01), which was
      prevented by treatment with losartan, an angiotensin (AT1) receptor inhibitor, or
      transfection with pSi-1. rMR-1 expression increased in ANG II-induced
      hypertrophied cardiomyocytes, and pSi-1 transfection abolished the upregulation.
      These findings suggest that MR-1 is associated with cardiac hypertrophy in rats
      in vivo and in vitro.

PMID- 16100250
TI  - Rapid dilation of arterioles with single contraction of hamster skeletal muscle.
AB  - Skeletal muscle blood flow increases rapidly with exercise onset, but little is
      known of where or how the rapid onset of vasodilation (ROV) is governed within
      the microcirculation. In the retractor muscle of anesthetized hamsters (n = 26),
      we tested the following: 1) where in the resistance network ROV occurred, 2) how
      microvascular responses were affected by the duration of contraction, and 3)
      whether ROV involved muscarinic receptor activation. Single tetanic contractions
      were evoked using supramaximal field stimulation (100 Hz) to depolarize motor end
      plates. In response to a 200-ms contraction, red blood cell (rbc) velocity
      (V(rbc)) in feed arteries (FA; rest: 17.8 +/- 2 mm/s) increased within 1 s; a
      transient first peak (P1; 50 +/- 7% increase) occurred at approximately 5 s; and
      a second peak (P2; 50 +/- 15% increase) occurred at approximately 15-20 s. For
      vasodilation, P1 increased in frequency from proximal FA (2/7) and 1A arterioles
      (2/7) to distal 2A (4/7) and 3A (7/8) arterioles (P < 0.05). Relative to resting
      (and maximal, 10 microM sodium nitroprusside) diameters, P1 increased from
      proximal (FA, 3 +/- 2% from 57 +/- 5 microm) to distal (3A, 27 +/- 6% from 14 +/-
      1 microm) vessel branches (P < 0.05). P2 was manifest in all vessels and
      increased relative to resting diameters from FA (11 +/- 3%) to 3A (36 +/- 6%)
      branches (P < 0.01). Extending a contraction from 200 to 1,000 ms (tension x time
      integral from 17 +/- 2 to 73 +/- 4 mN/mm2 x s) increased P1 and P2 for V(rbc) and
      for diameter (P < 0.05) while reducing the time of onset for P2 (P < 0.05).
      Superfusion with atropine (10 microM) attenuated P1 of vasodilation (200 ms
      contraction) from 26 +/- 8% to 6 +/- 2% (n = 7 across branches; P < 0.05) and
      reduced the diameter x time integral by 46 +/- 13% (P < 0.05) without changing
      P2. We conclude that ROV in the hamster retractor muscle is initiated in distal
      arterioles, increases with the duration of muscle contraction, and involves
      muscarinic receptor activation.

PMID- 16100251
TI  - Reduction in interaction between cGMP and cAMP in dog ventricular myocytes with
      hypertrophic failure.
AB  - Baseline function and signal transduction are depressed in hearts with
      hypertrophic failure. We tested the hypothesis that the effects of cGMP and its
      interaction with cAMP would be reduced in cardiac myocytes from hypertrophic
      failing hearts. Ventricular myocytes were isolated from control dogs, dogs with
      aortic valve stenosis hypertrophy, and dogs with pacing hypertrophic failure.
      Myocyte function was measured using a video edge detector. Cell contraction data
      were obtained at baseline, with 8-bromo-cGMP (10(-7), 10(-6), and 10(-5) M), with
      erythro-9-(2-hydroxy-3-nonyl)adenine [EHNA; a cAMP phosphodiesterase (PDE(2))
      inhibitor] plus 8-bromo-cGMP, or milrinone (a PDE(3) inhibitor) plus 8-bromo
      cGMP. Baseline percent shortening and maximal rates of shortening (R(max)) and
      relaxation were slightly reduced in hypertrophic myocytes and were significantly
      lower in failing myocytes (R(max): control dogs, 95.3 +/- 17.3; hypertrophy dogs,
      88.2 +/- 5.5; failure dogs, 53.2 +/- 6.4 mum/s). 8-Bromo-cGMP dose dependently
      reduced myocyte function in all groups. However, EHNA (10(-6) M) and milrinone
      (10(-6) M) significantly reduced the negative effects of cGMP on cell
      contractility in control and hypertrophy but not in failing myocytes (R(max) for
      control dogs: cGMP, -46%; +EHNA, -21%; +milrinone, -19%; for hypertrophy dogs:
      cGMP, -40%; +EHNA, -13%; +milrinone, -20%; for failure dogs: cGMP, -40%; +EHNA, 
      29%; +milrinone, -32%). Both combinations of EHNA-cGMP and milrinone-cGMP
      significantly increased intracellular cAMP in control, hypertrophic, and failing
      myocytes. These data indicated that the cGMP signaling pathway was preserved in
      hypertrophic failing cardiac myocytes. However, the interaction of cGMP with the
      cAMP signaling pathway was impaired in these failing myocytes.

PMID- 16100252
TI  - Cardiac extracellular matrix: a dynamic entity.

PMID- 16100253
TI  - Developmental structure-function insights from Tbx5(del/+) mouse model of Holt
      Oram syndrome.

PMID- 16100254
TI  - Chessboard of atrial fibrillation: reentry or focus? Single or multiple
      source(s)? Neurogenic or myogenic?

PMID- 16100255
TI  - Regulation of ACE2 and ANG-(1-7) in the aorta: new insights into the renin
      angiotensin system in the control of vascular function.

PMID- 16100256
TI  - Single-molecule FRET studies of important intermediates in the nucleocapsid
      protein-chaperoned minus-strand transfer step in HIV-1 reverse transcription.
AB  - The minus-strand transfer step of HIV-1 reverse transcription is chaperoned by
      the nucleocapsid protein (NC), which has been shown to facilitate the annealing
      between the transactivation response element (TAR) RNA and complementary TAR DNA
      stem-loop structures. In this work, potential intermediates in the mechanism of
      NC-chaperoned TAR DNA/TAR RNA annealing have been examined using single-molecule
      fluorescence resonance energy transfer. The interaction between TAR DNA and
      various DNA oligonucleotides designed to mimic the initial annealing step was
      monitored to capture potential intermediates along the reaction pathway. Two
      possible mechanisms of annealing were examined, namely nucleation through the
      3'/5' termini, termed the "zipper" complex, or nucleation through the hairpin
      loops in a "kissing" complex. Intermediates associated with both mechanisms were
      observed in the presence of NC, and the kinetics of formation of these
      intermediates were also measured. Thus, the single-molecule experiments support
      the notion that NC-assisted annealing of TAR DNA:TAR RNA may occur through
      multiple pathways.

PMID- 16100257
TI  - Homology modeling identifies C-terminal residues that contribute to the Ca2+
      sensitivity of a BKCa channel.
AB  - Activation of BK(Ca) channels by direct Ca(2+) binding and membrane
      depolarization occur via independent and additive molecular processes. The
      "calcium bowl" domain is critically involved in Ca(2+)-dependent gating, and we
      have hypothesized that a sequence within this domain may resemble an EF hand
      motif. Using a homology modeling strategy, it was observed that a single Ca(2+)
      ion may be coordinated by the oxygen-containing side chains of residues within
      the calcium bowl (i.e., (912)ELVNDTNVQFLD(923)). To examine these predictions
      directly, alanine-substituted BK(Ca) channel mutants were expressed in HEK 293
      cells and the voltage and Ca(2+) dependence of macroscopic currents were examined
      in inside-out membrane patches. Over the range of 1-10 microM free Ca(2+), single
      point mutations (i.e., E912A and D923A) produced rightward shifts in the steady
      state conductance-voltage relations, whereas the mutants N918A or Q920A had no
      effect on Ca(2+)-dependent gating. The double mutant E912A/D923A displayed a
      synergistic shift in Ca(2+)-sensitive gating, as well as altered kinetics of
      current activation/deactivation. In the presence of 1, 10, and 80 mM cytosolic
      Mg(2+), this double mutation significantly reduced the Ca(2+)-induced free energy
      change associated with channel activation. Finally, mutations that altered
      sensitivity of the holo-channel to Ca(2+) also reduced direct (45)Ca binding to
      the calcium bowl domain expressed as a bacterial fusion protein. These findings,
      along with other recent data, are considered in the context of the calcium bowl's
      high affinity Ca(2+) sensor and the known properties of EF hands.

PMID- 16100258
TI  - A model for diffusion in white matter in the brain.
AB  - Diffusion of molecules in brain and other tissues is important in a wide range of
      biological processes and measurements ranging from the delivery of drugs to
      diffusion-weighted magnetic resonance imaging. Diffusion tensor imaging is a
      powerful noninvasive method to characterize neuronal tissue in the human brain in
      vivo. As a first step toward understanding the relationship between the measured
      macroscopic apparent diffusion tensor and underlying microscopic compartmental
      geometry and physical properties, we treat a white matter fascicle as an array of
      identical thick-walled cylindrical tubes arranged periodically in a regular
      lattice and immersed in an outer medium. Both square and hexagonal arrays are
      considered. The diffusing molecules may have different diffusion coefficients and
      concentrations (or densities) in different domains, namely within the tubes'
      inner core, membrane, myelin sheath, and within the outer medium. Analytical
      results are used to explore the effects of a large range of microstructural and
      compositional parameters on the apparent diffusion tensor and the degree of
      diffusion anisotropy, allowing the characterization of diffusion in normal
      physiological conditions as well as changes occurring in development, disease,
      and aging. Implications for diffusion tensor imaging and for the possible in situ
      estimation of microstructural parameters from diffusion-weighted MR data are
      discussed in the context of this modeling framework.

PMID- 16100260
TI  - Imaging fast SNARE mediated-membrane fusion in planar-supported bilayers.

PMID- 16100259
TI  - Compaction kinetics on single DNAs: purified nucleosome reconstitution systems
      versus crude extract.
AB  - Kinetics of compaction on single DNA molecules are studied by fluorescence
      videomicroscopy in the presence of 1), Xenopus egg extracts and 2), purified
      nucleosome reconstitution systems using a combination of histones with either the
      histone chaperone Nucleosome Assembly Protein (NAP-1) or negatively charged
      macromolecules such as polyglutamic acid and RNA. The comparison shows that the
      compaction rates can differ by a factor of up to 1000 for the same amount of
      histones, depending on the system used and on the presence of histone tails,
      which can be subjected to post-translational modifications. Reactions with
      purified reconstitution systems follow a slow and sequential mechanism,
      compatible with the deposition of one (H3-H4)(2) tetramer followed by two (H2A
      H2B) dimers. Addition of the histone chaperone NAP-1 increases both the rate of
      the reaction and the packing ratio of the final product. These stimulatory
      effects cannot be obtained with polyglutamic acid or RNA, suggesting that yNAP-1
      impact on the reaction cannot simply be explained in terms of charge screening.
      Faster compaction kinetics and higher packing ratios are reproducibly reached
      with extracts, indicating a role of additional components present in this system.
      Data are discussed and models proposed to account for the kinetics obtained in
      our single-molecule assay.

PMID- 16100261
TI  - Solution AFM studies of human Swi-Snf and its interactions with MMTV DNA and
      chromatin.
AB  - ATP-dependent nucleosome remodeling complexes are crucial for relieving
      nucleosome repression during transcription, DNA replication, recombination, and
      repair. Remodeling complexes can carry out a variety of reactions on chromatin
      substrates but precisely how they do so remains a topic of active inquiry. Here,
      a novel recognition atomic force microscopy (AFM) approach is used to
      characterize human Swi-Snf (hSwi-Snf) nucleosome remodeling complexes in
      solution. This information is then used to locate hSwi-Snf complexes bound to
      mouse mammary tumor virus promoter nucleosomal arrays, a natural target of hSwi
      Snf action, in solution topographic AFM images of surface-tethered arrays. By
      comparing the same individual chromatin arrays before and after hSwi-Snf
      activation, remodeling events on these arrays can be monitored in relation to the
      complexes bound to them. Remodeling is observed to be: inherently heterogeneous;
      nonprocessive; able to occur near and far from bound complexes; often associated
      with nucleosome height decreases. These height decreases frequently occur near
      sites of DNA release from chromatin. hSwi-Snf is usually incorporated into
      nucleosomal arrays, with multiple DNA strands entering into it from various
      directions, + or - ATP; these DNA paths can change after hSwi-Snf activation.
      hSwi-Snf appears to interact with naked mouse mammary tumor virus DNA somewhat
      differently than with chromatin and ATP activation of surface-bound DNA/hSwi-Snf
      produces no changes detectable by AFM.

PMID- 16100262
TI  - A stability pattern of protein hydrophobic mutations that reflects evolutionary
      structural optimization.
AB  - We have determined the effect of mutations involving isoleucine and valine (i.e.,
      mutations I-->V and V-->I) on the stability of Escherichia coli thioredoxin.
      Despite the similarity in chemical structure (V and I differ only in a methyl
      group), we find that many environments are optimized to a significant extent for
      either V or I. We find, furthermore, that a plot of effect of hydrophobic
      mutations on stability versus packing density shows a strikingly simple pattern
      that clearly reflects evolutionary structural optimization. The existence of such
      patterns suggests the possibility of rationalizing (and perhaps even predicting)
      mutation effects on protein stability on the basis of evolutionary models. By
      "evolutionary model" we specifically refer in this context to a model for
      mutation effects on stability in which certain physical features of the mutated
      residue environments are evaluated from an assumption regarding how such
      environments have been selected during protein evolution (as opposed to a purely
      "physical model" in which those features would be derived from some kind of
      energetics analysis of the protein structural characteristics). To illustrate
      this novel approach and provide general guidelines for its application, we
      develop here a simple evolutionary model that successfully explains the effect of
      the I<-->V mutations on thioredoxin stability.

PMID- 16100263
TI  - Mimicry of a host anion channel by a Helicobacter pylori pore-forming toxin.
AB  - Bacterial pore-forming toxins have traditionally been thought to function either
      by causing an essentially unrestricted flux of ions and molecules across a
      membrane or by effecting the transmembrane transport of an enzymatically active
      bacterial peptide. However, the Helicobacter pylori pore-forming toxin, VacA,
      does not appear to function by either of these mechanisms, even though at least
      some of its effects in cells are dependent on its pore-forming ability. Here we
      show that the VacA channel exhibits two of the most characteristic
      electrophysiological properties of a specific family of cellular channels, the
      ClC channels: an open probability dependent on the molar ratio of permeable ions
      and single channel events resolvable as two independent, voltage-dependent
      transitions. The sharing of such peculiar properties by VacA and host ClC
      channels, together with their similar magnitudes of conductance, ion
      selectivities, and localization within eukaryotic cells, suggests a novel
      mechanism of toxin action in which the VacA pore largely mimics the
      electrophysiological behavior of a host channel, differing only in the membrane
      potential at which it closes. As a result, VacA can perturb, but not necessarily
      abolish, the homeostatic ionic imbalance across a membrane and so change cellular
      physiology without necessarily jeopardizing vitality.

PMID- 16100264
TI  - Neutrophil-bead collision assay: pharmacologically induced changes in membrane
      mechanics regulate the PSGL-1/P-selectin adhesion lifetime.
AB  - Visualization of flowing neutrophils colliding with adherent 1-mum-diameter beads
      presenting P-selectin allowed the simultaneous measurement of collision
      efficiency (epsilon), membrane tethering fraction (f), membrane tether growth
      dynamics, and PSGL-1/P-selectin binding lifetime. For 1391 collisions analyzed
      over venous wall shear rates from 25 to 200 s(-1), epsilon decreased from 0.17 to
      0.004, whereas f increased from 0.15 to 0.70, and the average projected membrane
      tether length, L(tether)(m), increased from 0.35 mum to approximately 2.0 mum
      over this shear range. At all shear rates tested, adhesive collisions lacking
      membrane tethers had average bond lifetimes less than those observed for
      collisions with tethers. For adhesive collisions that failed to form membrane
      tethers, the regressed Bell parameters (consistent with single bond Monte Carlo
      simulation) were zero-stress off-rate, k(off)(0) = 0.56 s(-1) and reactive
      compliance, r = 0.10 nm, similar to published atomic force microscopy (AFM)
      measurements. For all adhesion events (+/- tethers), the bond lifetime
      distributions were more similar to those obtained by rolling assay and best
      simulated by Monte Carlo with the above Bell parameters and an average of 1.48
      bonds (n = 1 bond (67%), n = 2 (22%), and n = 3-5 (11%)). For collisions at 100
      s(-1), pretreatment of neutrophils with actin depolymerizing agents, latrunculin
      or cytochalasin D, had no effect on epsilon, but increased L(tether)(m) by 1.74-
      or 2.65-fold and prolonged the average tether lifetime by 1.41- or 1.65-fold,
      respectively. Jasplakinolide, an actin polymerizing agent known to cause
      blebbing, yielded results similar to the depolymerizing agents. Conversely,
      cholesterol-depletion with methyl-beta-cyclodextrin or formaldehyde fixation had
      no effect on epsilon, but reduced L(tether)(m) by 66% or 97% and reduced the
      average tether lifetime by 30% or 42%, respectively. The neutrophil-bead
      collision assay combines advantages of atomic force microscopy (small contact
      zone), aggregometry (discrete interactions), micropipette manipulation (tether
      visualization), and rolling assays (physiologic flow loading). Membrane tether
      growth can be enhanced or reduced pharmacologically with consequent effects on
      PSGL-1/P-selectin lifetimes.

PMID- 16100265
TI  - The catalytic copper of peptidylglycine alpha-hydroxylating monooxygenase also
      plays a critical structural role.
AB  - Many bioactive peptides require amidation of their carboxy terminus to exhibit
      full biological activity. Peptidylglycine alpha-hydroxylating monooxygenase (PHM;
      EC 1.14.17.3), the enzyme that catalyzes the first of the two steps of this
      reaction, is composed of two domains, each of which binds one copper atom (CuH
      and CuM). The CuM site includes Met(314) and two His residues as ligands.
      Mutation of Met(314) to Ile inactivates PHM, but has only a minimal effect on the
      EXAFS spectrum of the oxidized enzyme, implying that it contributes only
      marginally to stabilization of the CuM site. To characterize the role of Met(314)
      as a CuM ligand, we determined the structure of the Met(314)Ile-PHM mutant. Since
      the mutant protein failed to crystallize in the conditions of the original wild
      type protein, this structure determination required finding a new crystal form.
      The Met(314)Ile-PHM mutant structure confirms that the mutation does not abolish
      CuM binding to the enzyme, but causes other structural perturbations that affect
      the overall stability of the enzyme and the integrity of the CuH site. To
      eliminate possible effects of crystal contacts, we redetermined the structure of
      wt-PHM in the Met(314)Ile-PHM crystal form and showed that it does not differ
      from the structure of wild-type (wt)-PHM in the original crystals. Met(314)Ile
      PHM was also shown to be less stable than wt-PHM by differential scanning
      calorimetry. Both structural and calorimetric studies point to a structural role
      for the CuM site, in addition to its established catalytic role.

PMID- 16100266
TI  - Comparison of mode analyses at different resolutions applied to nucleic acid
      systems.
AB  - More than two decades of different types of mode analyses has shown that these
      techniques can be useful in describing large-scale motions in protein systems. A
      number of mode analyses are available and include quasiharmonics, classical
      normal mode, block normal mode, and the elastic network model. Each of these
      methods has been validated for protein systems and this variety allows
      researchers to choose the technique that gives the best compromise between
      computational cost and the level of detail in the calculation. These same
      techniques have not been systematically tested for nucleic acid systems, however.
      Given the differences in interactions and structural features between nucleic
      acid and protein systems, the validity of these techniques in the protein regime
      cannot be directly translated into validity in the nucleic acid realm. In this
      work, we investigate the usefulness of the above mode analyses as applied to two
      RNA systems, i.e., the hammerhead ribozyme and a guanine riboswitch. We show that
      classical normal-mode analysis can match the magnitude and direction of residue
      fluctuations from the more detailed, anharmonic technique, quasiharmonic analysis
      of a molecular dynamics trajectory. The block normal-mode approximation is shown
      to hold in the nucleic acid systems studied. Only the mode analysis at the lowest
      level of detail, the elastic network model, produced mixed results in our
      calculations. We present data that suggest that the elastic network model, with
      the popular parameterization, is not best suited for systems that do not have a
      close packed structure; this observation also hints at why the elastic network
      model has been found to be valid for many globular protein systems. The different
      behaviors of block normal-mode analysis and the elastic network model, which
      invoke similar degrees of coarse-graining to the dynamics but use different
      potentials, suggest the importance of applying a heterogeneous potential function
      in a robust analysis of the dynamics of biomolecules, especially those that are
      not closely packed. In addition to these comparisons, we briefly discuss insights
      into the conformational space available to the hammerhead ribozyme.

PMID- 16100267
TI  - The entropic cost of protein-protein association: a case study on
      acetylcholinesterase binding to fasciculin-2.

PMID- 16100268
TI  - Diffusion, mixing, and associated dye effects in DNA-microarray hybridizations.
AB  - Typical DNA microarrays utilize diffusion of dye-labeled cDNA probes followed by
      sequence-specific hybridization to immobilized targets. Here we experimentally
      estimated the distance typical probes travel during static 16-h hybridizations.
      Probes labeled with Cy3 and Cy5 were individually introduced to opposite sides of
      a microarray with minimal convective mixing. Oppositely labeled probes diffused
      across the initial front separating the two solutions, generating a zone with
      both dyes present. Diffusion-distance estimates for Cy3- and Cy5-labeled cDNAs
      were 3.8 mm and 2.6 mm, respectively, despite having almost identical molecular
      masses. In separate 16-h hybridization experiments with oppositely labeled probes
      premixed, arrays that were continuously mixed had 15-20% higher signal
      intensities than arrays hybridized statically. However, no change was observed in
      the Cy3/Cy5 signal intensity ratio between continuously mixed and static
      hybridizations. This suggests that the observed dye bias in diffusion-distance
      estimates results from differences in the detection limits of Cy3 and Cy5-labeled
      cDNA, a potential concern for array data on low-abundance transcripts. Our
      conservative diffusion-distance estimates indicate that replicate targets >7.6 mm
      apart will not compete for scarce probes. Also, raising the microarray gap height
      would delay the onset of diffusion-limited hybridization by increasing the amount
      of available probe.

PMID- 16100269
TI  - Microtubules: mechanical meets chemical.

PMID- 16100270
TI  - Dissecting homo-heptamer thermodynamics by isothermal titration calorimetry:
      entropy-driven assembly of co-chaperonin protein 10.
AB  - Normally, isothermal titration calorimetry (ITC) is used to study binding
      reactions between two different biomolecules. Self-association processes leading
      to homo-oligomeric complexes have usually not been studied by ITC; instead,
      methods such as spectroscopy and analytical ultracentrifugation, which only
      provide affinity and Gibbs-free energy (i.e., K(D) and DeltaG), are employed. We
      here demonstrate that complete thermodynamic descriptions (i.e., K(D), DeltaG,
      DeltaH, and DeltaS) for self-associating systems can be obtained by ITC-dilution
      experiments upon proper analysis. We use this approach to probe the dissociation
      (and thus association) equilibrium for the heptameric co-chaperonin proteins 10
      (cpn10) from Aquifex aeolicus (Aacpn10-del25) and human mitochondria (hmcpn10).
      We find that the midpoints for the heptamer-monomer equilibrium occur at 0.51 +/-
      0.03 microM and 3.5 +/- 0.1 microM total monomer concentration (25 degrees C),
      for Aacpn10-del25 and hmcpn10, respectively. For both proteins, association
      involves endothermic enthalpy and positive entropy changes; thus, the reactions
      are driven by the entropy increase. This is in accord with the release of ordered
      water molecules and, for the thermophilic variant, a relaxation of monomer
      tertiary structure when the heptamers form.

PMID- 16100271
TI  - Diffusion correlation NMR spectroscopic study of anisotropic diffusion of water
      in plant tissues.
AB  - The anisotropic diffusion of water in chive (Allium schoenoprasum) tissues has
      been investigated using two-dimensional nuclear magnetic resonance methods:
      diffusion-diffusion correlation spectroscopy and diffusion-relaxation correlation
      spectroscopy. Corresponding one-dimensional T2 and diffusion measurements confirm
      independently the results of the two-dimensional investigations. In particular
      the diffusion-diffusion correlation spectroscopy method proves to be very
      powerful in resolving the different components of the diffusion tensor at
      different sites in the sample.

PMID- 16100272
TI  - Effects of soman inhibition and of structural differences on cholinesterase
      molecular dynamics: a neutron scattering study.
AB  - Incoherent elastic neutron scattering experiments on members of the
      cholinesterase family were carried out to investigate how molecular dynamics is
      affected by covalent inhibitor binding and by differences in primary and
      quaternary structure. Tetrameric native and soman-inhibited human
      butyrylcholinesterase (HuBChE) as well as native dimeric Drosophila melanogaster
      acetylcholinesterase (DmAChE) hydrated protein powders were examined. Atomic mean
      square displacements (MSDs) were found to be identical for native HuBChE and for
      DmAChE in the whole temperature range examined, leading to the conclusion that
      differences in activity and substrate specificity are not reflected by a global
      modification of subnanosecond molecular dynamics. MSDs of native and soman
      inhibited HuBChE were identical below the thermal denaturation temperature of the
      native enzyme, indicating a common mean free-energy surface. Denaturation of the
      native enzyme is reflected by a relative increase of MSDs consistent with
      entropic stabilization of the unfolded state. The results suggest that the
      stabilization of HuBChE phosphorylated by soman is due to an increase in free
      energy of the unfolded state due to a decrease in entropy.

PMID- 16100273
TI  - Phase behavior and nanoscale structure of phospholipid membranes incorporated
      with acylated C14-peptides.
AB  - The thermotropic phase behavior and lateral structure of
      dipalmitoylphosphatidylcholine (DPPC) lipid bilayers containing an acylated
      peptide has been characterized by differential scanning calorimetry (DSC) on
      vesicles and atomic force microscopy (AFM) on mica-supported bilayers. The
      acylated peptide, which is a synthetic decapeptide N-terminally linked to a C14
      acyl chain (C14-peptide), is incorporated into DPPC bilayers in amounts ranging
      from 0-20 mol %. The calorimetric scans of the two-component system demonstrate a
      distinct influence of the C14-peptide on the lipid bilayer thermodynamics. This
      is manifested as a concentration-dependent downshift of both the main phase
      transition and the pretransition. In addition, the main phase transition peak is
      significantly broadened, indicating phase coexistence. In the AFM imaging scans
      we found that the C14-peptide, when added to supported gel phase DPPC bilayers,
      inserts preferentially into preexisting defect regions and has a noticeable
      influence on the organization of the surrounding lipids. The presence of the C14
      peptide gives rise to a laterally heterogeneous bilayer structure with coexisting
      lipid domains characterized by a 10 A height difference. The AFM images also show
      that the appearance of the ripple phase of the DPPC lipid bilayers is unaffected
      by the C14-peptide. The experimental results are supported by molecular dynamics
      simulations, which show that the C14-peptide has a disordering effect on the
      lipid acyl chains and causes a lateral expansion of the lipid bilayer. These
      effects are most pronounced for gel-like bilayer structures and support the
      observed downshift in the phase-transition temperature. Moreover, the molecular
      dynamics data indicate a tendency of a tryptophan residue in the peptide sequence
      to position itself in the bilayer headgroup region.

PMID- 16100274
TI  - Periodic patterns of actin turnover in lamellipodia and lamellae of migrating
      epithelial cells analyzed by quantitative Fluorescent Speckle Microscopy.
AB  - We measured actin turnover in lamellipodia and lamellae of migrating cells, using
      quantitative Fluorescent Speckle Microscopy. Lamellae disassembled at low rates
      from the front to the back. However, the dominant feature in their turnover was a
      spatially random pattern of periodic polymerization and depolymerization moving
      with the retrograde flow. Power spectra contained frequencies between 0.5 and 1
      cycle/min. The spectra remained unchanged when applying Latrunculin A and
      Jasplakinolide in low doses, except that additional frequencies occurred beyond 1
      cycle/min. Whereas Latrunculin did not change the rate of mean disassembly,
      Jasplakinolide halted it completely, indicating that the steady state and the
      dynamics of actin turnover are differentially affected by pharmacological agents.
      Lamellipodia assembled in recurring bursts at the leading edge and disassembled
      approximately 2.5 microm behind. Events of polymerization correlated spatially
      and temporally with transient formation of Arp2/3 clusters. In lamellae, Arp2/3
      accumulation and polymerization correlated only spatially, suggesting an Arp2/3
      independent mechanism for filament nucleation. To acquire these data we had to
      enhance the resolution of quantitative Fluorescent Speckle Microscopy to the
      submicron level. Several algorithmic advances in speckle image processing are
      described enabling the analysis of kinetic and kinematic activities of polymer
      networks at the level of single speckles.

PMID- 16100275
TI  - Radial compression of microtubules and the mechanism of action of taxol and
      associated proteins.
AB  - Microtubules (MTs) are hollow cylindrical polymers composed of alphabeta-tubulin
      heterodimers that align head-to-tail in the MT wall, forming linear
      protofilaments that interact laterally. We introduce a probe of the
      interprotofilament interactions within MTs and show that this technique gives
      insight into the mechanisms by which MT-associated proteins (MAPs) and taxol
      stabilize MTs. In addition, we present further measurements of the mechanical
      properties of MT walls, MT-MT interactions, and the entry of polymers into the MT
      lumen. These results are obtained from a synchrotron small angle x-ray
      diffraction (SAXRD) study of MTs under osmotic stress. Above a critical osmotic
      pressure, P(cr), we observe rectangular bundles of MTs whose cross sections have
      buckled to a noncircular shape; further increases in pressure continue to distort
      MTs elastically. The P(cr) of approximately 600 Pa provides, for the first time,
      a measure of the bending modulus of the interprotofilament bond within an MT. The
      presence of neuronal MAPs greatly increases P(cr), whereas surprisingly, the
      cancer chemotherapeutic drug taxol, which suppresses MT dynamics and inhibits MT
      depolymerization, does not affect the interprotofilament interactions. This SAXRD
      osmotic stress technique, which has enabled measurements of the mechanical
      properties of MTs, should find broad application for studying interactions
      between MTs and of MTs with MAPs and MT-associated drugs.

PMID- 16100276
TI  - Interaction between lipid monolayers and poloxamer 188: an X-ray reflectivity and
      diffraction study.
AB  - The mechanism by which poloxamer 188 (P188) seals a damaged cell membrane is
      examined using the lipid monolayer as a model system. X-ray reflectivity and
      grazing-incidence x-ray diffraction results show that at low nominal lipid
      density, P188, by physically occupying the available area and phase separating
      from the lipids, forces the lipid molecules to pack tightly and restore the
      barrier function of the membrane. Upon compression to bilayer equivalent
      pressure, P188 is squeezed out from the lipid monolayer, allowing a graceful exit
      of P188 when the membrane integrity is restored.

PMID- 16100277
TI  - Ligand binding modulates the mechanical stability of dihydrofolate reductase.
AB  - We use single-molecule force spectroscopy to demonstrate that the mechanical
      stability of the enzyme dihydrofolate reductase (DHFR) is modulated by ligand
      binding. In the absence of bound ligands, DHFR extends at very low forces,
      averaging 27 pN, without any characteristic mechanical fingerprint. By contrast,
      in the presence of micromolar concentrations of the ligands methotrexate,
      nicotinamide adenine dihydrogen phosphate, or dihydrofolate, much higher forces
      are required (82 +/- 18 pN, 98 +/- 15 pN, and 83 +/- 16 pN, respectively) and a
      characteristic fingerprint is observed in the force-extension curves. The
      increased mechanical stability triggered by these ligands is not additive. Our
      results explain the large reduction in the degradation rate of DHFR, in the
      presence of its ligands. Our observations support the view that the rate-limiting
      step in protein degradation by adenosine triphosphate-dependent proteases is the
      mechanical unfolding of the target protein.

PMID- 16100278
TI  - Multiple-bond kinetics from single-molecule pulling experiments: evidence for
      multiple NCAM bonds.
AB  - The kinetic parameters of single bonds between neural cell adhesion molecules
      were determined from atomic force microscope measurements of the forced
      dissociation of the homophilic protein-protein bonds. The analytical approach
      described provides a systematic procedure for obtaining rupture kinetics for
      single protein bonds from bond breakage frequency distributions obtained from
      single-molecule pulling experiments. For these studies, we used the neural cell
      adhesion molecule (NCAM), which was recently shown to form two independent
      protein bonds. The analysis of the bond rupture data at different loading rates,
      using the single-bond full microscopic model, indicates that the breakage
      frequency distribution is most sensitive to the distance to the transition state
      and least sensitive to the molecular spring constant. The analysis of bond
      failure data, however, motivates the use of a double-bond microscopic model that
      requires an additional kinetic parameter. This double-bond microscopic model
      assumes two independent NCAM-NCAM bonds, and more accurately describes the
      breakage frequency distribution, particularly at high loading rates. This finding
      agrees with recent surface-force measurements, which showed that NCAM forms two
      spatially distinct bonds between opposed proteins.

PMID- 16100279
TI  - Molecular dynamics study of bipolar tetraether lipid membranes.
AB  - Membranes composed of bipolar tetraether lipids have been studied by a series of
      25-ns molecular dynamics simulations to understand the microscopic structure and
      dynamics as well as membrane area elasticity. By comparing macrocyclic and
      acyclic tetraether and diether archaeal lipids, the effect of tail linkage of the
      two phytanyl-chained lipids on the membrane properties is elucidated. Tetraether
      lipids show smaller molecular area and lateral mobility. For the latter,
      calculated diffusion coefficients are indeed one order-of-magnitude smaller than
      that of the diether lipid. These two tetraether membranes are alike in many
      physical properties except for membrane area elasticity. The macrocyclic
      tetraether membrane shows a higher elastic area expansion modulus than its
      acyclic counterpart by a factor of three. Free energy profiles of a water
      molecule crossing the membranes show no major difference in barrier height;
      however, a significant difference is observed near the membrane center due to the
      lack of the slip-plane in tetraether membranes.

PMID- 16100280
TI  - Effect of structural transition of the host assembly on dynamics of an ion
      channel peptide: a fluorescence approach.
AB  - Structural transition can be induced in charged micelles by increasing the ionic
      strength of the medium. We have monitored the organization and dynamics of the
      functionally important tryptophan residues of gramicidin in spherical and rod
      shaped sodium dodecyl sulfate micelles utilizing a combination of wavelength
      selective fluorescence and related fluorescence approaches. Our results show that
      tryptophans in gramicidin, present in the single-stranded beta(6.3) conformation,
      experience slow solvent relaxation giving rise to red edge excitation shift in
      spherical and rod-shaped micelles. In addition, changes in fluorescence
      polarization with increasing excitation or emission wavelength reinforce that the
      gramicidin tryptophans are localized in motionally restricted regions of these
      micelles. Fluorescence quenching experiments using acrylamide as a quencher of
      tryptophan fluorescence show that there is reduced water penetration in rod
      shaped micelles. Taken together, we show that gramicidin conformation and
      dynamics is sensitive to the salt-induced structural transition in charged
      micelles. In addition, these results demonstrate that deformation of the host
      assembly could modulate protein conformation and dynamics.

PMID- 16100281
TI  - Time- and voltage-dependent components of Kv4.3 inactivation.
AB  - Kv4.3 inactivation is a complex multiexponential process, which can occur from
      both closed and open states. The fast component of inactivation is modulated by
      the N-terminus, but the mechanisms mediating the other components of inactivation
      are controversial. We studied inactivation of Kv4.3 expressed in Xenopus laevis
      oocytes, using the two-electrode voltage-clamp technique. Inactivation during
      2000 ms pulses at potentials positive to the activation threshold was described
      by three exponents (46 +/- 3, 152 +/- 13, and 930 +/- 50 ms at +50 mV, n = 7)
      whereas closed-state inactivation (at potentials below threshold) was described
      by two exponents (1079 +/- 119 and 3719 +/- 307 ms at -40 mV, n = 9). The fast
      component of open-state inactivation was dominant at potentials positive to -20
      mV. Negative to -30 mV, the intermediate and slow components dominated
      inactivation. Inactivation properties were dependent on pulse duration. Recovery
      from inactivation was strongly dependent on voltage and pulse duration. We
      developed an 11-state Markov model of Kv4.3 gating that incorporated a direct
      transition from the open-inactivated state to the closed-inactivated state.
      Simulations with this model reproduced open- and closed-state inactivation,
      isochronal inactivation relationships, and reopening currents. Our data suggest
      that inactivation can proceed primarily from the open state and that multiple
      inactivation components can be identified.

PMID- 16100282
TI  - I-domain of lymphocyte function-associated antigen-1 mediates rolling of
      polystyrene particles on ICAM-1 under flow.
AB  - In their active state, beta(2)-integrins, such as LFA-1, mediate the firm arrest
      of leukocytes by binding intercellular adhesion molecules (ICAMs) expressed on
      endothelium. Although the primary function of LFA-1 is assumed to be the ability
      to mediate firm adhesion, recent work has shown that LFA-1 can contribute to cell
      tethering and rolling under hydrodynamic flow, a role previously largely
      attributed to the selectins. The inserted (I) domain of LFA-1 has recently been
      crystallized in the wild-type (wt) and locked-open conformations and has been
      shown to, respectively, support rolling and firm adhesion under flow when
      expressed in alpha(L)beta(2) heterodimers or as isolated domains on cells. Here,
      we report results from cell-free adhesion assays where wt I-domain-coated
      polystyrene particles were allowed to interact with ICAM-1-coated surfaces in
      shear flow. We show that wt I-domain can independently mediate the capture of
      particles from flow and support their rolling on ICAM-1 surfaces in a manner
      similar to how carbohydrate-selectin interactions mediate rolling. Adhesion is
      specific and blocked by appropriate antibodies. We also show that the rolling
      velocity of I-domain-coated particles depends on the wall shear stress in flow
      chamber, I-domain site density on microsphere surfaces, and ICAM-1 site density
      on substrate surfaces. Furthermore, we show that rolling is less sensitive to
      wall shear stress and ICAM-1 substrate density at high density of I-domain on the
      microsphere surface. Computer simulations using adhesive dynamics can recreate
      bead rolling dynamics and show that the mechanochemical properties of ICAM-1-I
      domain interactions are similar to those of carbohydrate-selectin interactions.
      Understanding the biophysics of adhesion mediated by the I-domain of LFA-1 can
      elucidate the complex roles this integrin plays in leukocyte adhesion in
      inflammation.

PMID- 16100283
TI  - The E-hook of tubulin interacts with kinesin's head to increase processivity and
      speed.
AB  - Kinesins are dimeric motor proteins that move processively along microtubules. It
      has been proposed that the processivity of conventional kinesins is increased by
      electrostatic interactions between the positively charged neck of the motor and
      the negatively charged C-terminus of tubulin (E-hook). In this report we
      challenge this anchoring hypothesis by studying the motility of a fast fungal
      kinesin from Neurospora crassa (NcKin). NcKin is highly processive despite
      lacking the positive charges in the neck. We present a detailed analysis of how
      proteolytic removal of the E-hook affects truncated monomeric and dimeric
      constructs of NcKin. Upon digestion we observe a strong reduction of the
      processivity and speed of dimeric motor constructs. Monomeric motors with
      truncated or no neck display the same reduction of microtubule gliding speed as
      dimeric constructs, suggesting that the E-hook interacts with the head only. The
      E-hook has no effect on the strongly bound states of NcKin as microtubule
      digestion does not alter the stall forces produced by single dimeric motors,
      suggesting that the E-hook affects the interaction site of the kinesin.ADP-head
      and the microtubule. In fact, kinetic and binding experiments indicate that
      removal of the E-hook shifts the binding equilibrium of the weakly attached
      kinesin.ADP-head toward a more strongly bound state, which may explain reduced
      processivity and speed on digested microtubules.

PMID- 16100285
TI  - Inflammatory response of tracheobronchial epithelial cells to endotoxin.
AB  - Respiratory epithelial cells play a crucial role in the inflammatory response in
      endotoxin-induced lung injury, an experimental model for acute lung injury. To
      determine the role of epithelial cells in the upper respiratory compartment in
      the inflammatory response to endotoxin, we exposed tracheobronchial epithelial
      cells (TBEC) to lipopolysaccharide (LPS). Expression of inflammatory mediators
      was analyzed, and the biological implications were assessed using chemotaxis and
      adherence assays. Epithelial cell necrosis and apoptosis were determined to
      identify LPS-induced cell damage. Treatment of TBEC with LPS induced enhanced
      protein expression of cytokines and chemokines (increases of 235-654%, P < 0.05),
      with increased chemotactic activity regarding neutrophil recruitment. Expression
      of the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion
      molecule-1 (VCAM-1) was enhanced by 52-101% (P < 0.0001). This upregulation led
      to increased adhesion of neutrophils, with >95% adherence to TBEC after LPS
      stimulation, which could be blocked by either ICAM-1 (69%) or VCAM-1 antibodies
      (55%) (P < 0.05). Enhanced neutrophil-induced necrosis of TBEC was observed when
      TBEC were exposed to LPS. Reduced neutrophil adherence by ICAM-1 or VCAM-1
      antibodies resulted in significantly lower TBEC death (52 and 34%, respectively,
      P < 0.05). Therefore, tight adherence of neutrophils to TBEC appears to promote
      epithelial cell killing. In addition to indirect effector cell-induced TBEC
      death, direct LPS-induced cell damage was seen with increased apoptosis rate in
      LPS-stimulated TBEC (36% increase of caspase-3, P < 0.01). These data provide
      evidence that LPS induces TBEC killing in a necrosis- and apoptosis-dependent
      manner.

PMID- 16100284
TI  - Cell-transistor coupling: investigation of potassium currents recorded with p-
      and n-channel FETs.
AB  - Microelectronic-based biosensors that allow noninvasive measurement of cell
      activity are in the focus of current developments, however, the mechanisms
      underlying the cell-transistor coupling are not completely understood. In
      particular, characteristic properties of the extracellular voltage response such
      as the waveform and amplitude are not satisfactorily described by electrical
      circuit models. Here we examine the electrical coupling between a nonmetallized
      field-effect transistor (FET) and a cell line expressing a voltage-gated EAG K+
      channel. The activation kinetics of this channel depends on the voltage pulse
      protocol and extracellular divalent cations. This feature allows testing, whether
      the extracellular voltage signal recorded with the FET faithfully tracks the
      current simultaneously recorded with the patch-clamp technique. We find that the
      FET signals contain different kinetic components that cannot be entirely
      explained by equivalent electrical-circuit models. Rather, we suggest that
      changes in ion concentration in the small cleft between cell and FET may change
      the surface potential of the FET. This study provides evidence that the
      electrochemical processes at the cell-transistor interface are complex and that
      at least two different mechanisms contribute to the shape and amplitude of
      transistor signals.

PMID- 16100286
TI  - Connective tissue growth factor and vascular endothelial growth factor from
      airway smooth muscle interact with the extracellular matrix.
AB  - Airway remodeling describes the structural changes that occur in the asthmatic
      airway that include airway smooth muscle hyperplasia, increases in vascularity
      due to angiogenesis, and thickening of the basement membrane. Our aim in this
      study was to examine the effect of transforming growth factor-beta on the release
      of connective tissue growth factor and vascular endothelial growth factor from
      human airway smooth muscle cells derived from asthmatic and nonasthmatic
      patients. In addition we studied the immunohistochemical localization of these
      cytokines in the extracellular matrix after stimulating bronchial rings with
      transforming growth factor-beta. Connective tissue growth factor and vascular
      endothelial growth factor were released from both cell types and colocalized in
      the surrounding extracellular matrix. Prostaglandin E2 inhibited the increase in
      connective tissue growth factor mRNA but augmented the release of vascular
      endothelial growth factor. Matrix metalloproteinase-2 decreased the amount of
      connective tissue growth factor and vascular endothelial growth factor, but not
      fibronectin deposited in the extracellular matrix. This report provides the first
      evidence that connective tissue growth factor may anchor vascular endothelial
      growth factor to the extracellular matrix and that this deposition is decreased
      by matrix metalloproteinase-2 and prostaglandin E2. This relationship has the
      potential to contribute to the changes that constitute airway remodeling,
      therefore providing a novel focus for therapeutic intervention in asthma.

PMID- 16100287
TI  - Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells:
      implications for lung development.
AB  - Pulmonary neuroendocrine cells (PNEC) produce amine (serotonin, 5-HT) and
      peptides (e.g., bombesin, calcitonin) with growth factor-like properties and are
      thought to play an important role in lung development. Because physical forces
      are essential for lung growth and development, we investigated the effects of
      mechanical strain on 5-HT release in PNEC freshly isolated from rabbit fetal lung
      and in the PNEC-related tumor H727 cell line. Cultures exposed to sinusoidal
      cyclic stretch showed a significant 5-HT release inhibitable with gadolinium
      chloride (10 nM), a blocker of mechanosensitive channels. In contrast to hypoxia
      (Po2 approximately 20 mmHg), stretch-induced 5-HT release was not affected by
      Ca2+-free medium or nifedipine (50 microM), excluding the exocytic pathway. In
      H727 cells, stretch failed to release calcitonin, a peptide stored within dense
      core vesicles (DCV), whereas hypoxia caused massive calcitonin release. 5-HT
      released by mechanical stretch is derived predominantly from the cytoplasmic
      pool, because it is rapid ( approximately 5 min) and is releasable from early (20
      days of gestation) fetal PNEC containing few DCV. Both mechanical stretch and
      hypoxia upregulated expression of tryptophan hydroxylase, the rate-limiting
      enzyme of 5-HT synthesis. We conclude that mechanical strain is an important
      physiological stimulus for the release of 5-HT from PNEC via mechanosensitive
      channels with potential effects on lung development and resorption of lung fluid
      at the time of birth.

PMID- 16100288
TI  - Blockade of tissue factor-factor X binding attenuates sepsis-induced respiratory
      and renal failure.
AB  - Tissue factor expression in sepsis activates coagulation in the lung, which
      potentiates inflammation and leads to fibrin deposition. We hypothesized that
      blockade of factor X binding to the tissue factor-factor VIIa complex would
      prevent sepsis-induced damage to the lungs and other organs. Acute lung injury
      was produced in 15 adult baboons primed with killed Escherichia coli [1 x 10(9)
      colony-forming units (CFU)/kg], and then 12 h later, they were given 1 x 10(10)
      CFU/kg live E. coli by infusion. Two hours after live E. coli, animals received
      antibiotics with or without monoclonal antibody to tissue factor intravenously to
      block tissue factor-factor X binding. The animals were monitored physiologically
      for 34 h before being killed and their tissue harvested. The antibody treatment
      attenuated abnormalities in gas exchange and lung compliance, preserved renal
      function, and prevented tissue neutrophil influx and bowel edema relative to
      antibiotics alone (all P < 0.05). It also attenuated fibrinogen depletion (P <
      0.01) and decreased proinflammatory cytokines, e.g., IL-6 and -8 (P < 0.01), in
      systemic and alveolar compartments. Similar protective effects of the antibody on
      IL-6 and -8 expression and permeability were found in lipopolysaccharide
      stimulated endothelial cells. Blockade of factor X binding to the tissue factor
      factor VIIa complex attenuates lung and organ injuries in established E. coli
      sepsis by attenuating the neutrophilic response and inflammatory pathways.

PMID- 16100289
TI  - Transgenic extracellular superoxide dismutase protects postnatal alveolar
      epithelial proliferation and development during hyperoxia.
AB  - Transgenic (TG) human (h) extracellular superoxide dismutase (EC-SOD) targeted to
      type II cells protects postnatal newborn mouse lung development against hyperoxia
      by unknown mechanisms. Because alveolar development depends on timely
      proliferation of type II epithelium and differentiation to type I epithelium, we
      measured proliferation in bronchiolar and alveolar (surfactant protein C
      positive) epithelium in air and 95% O2-exposed wild-type (WT) and TG hEC-SOD
      newborn mice at postnatal days 3, 5, and 7 (P3-P7), traversing the transition
      from saccular to alveolar stages. We found that TG hEC-SOD ameliorated the 95% O2
      impaired bromodeoxyuridine uptake in alveolar and bronchiolar epithelium at P3,
      but not at P5 and P7, when overall epithelial proliferation rates were lower in
      air-exposed WT mice. Mouse EC-, CuZn-, and Mn-SOD expression were unaffected by
      hyperoxia or genotype. TG mice had less DNA damage than 95% O2-exposed WT mice at
      P3, measured by TdT-mediated dUTP nick end labeling (P < 0.05). Hyperoxia induced
      cell-cycle inhibitory protein p21cip/waf mRNA at P3, WT > TG, P = 0.06. 95% O2
      impaired apical expression of type I cell alpha protein (T1alpha) in WT but not
      in TG mice at P3 and increased T1alpha in WT and TG mice at P7. Reducing the 95%
      O2-induced impairment of epithelial proliferation at a critical window of lung
      development was associated with protection against DNA damage and preservation of
      apical T1alpha expression at P3.

PMID- 16100290
TI  - Involvement of the platelet-activating factor receptor in host defense against
      Streptococcus pneumoniae during postinfluenza pneumonia.
AB  - Although influenza infection alone may lead to pneumonia, secondary bacterial
      infections are a much more common cause of pneumonia. Streptococcus pneumoniae is
      the most frequently isolated causative pathogen during postinfluenza pneumonia.
      Considering that S. pneumoniae utilizes the platelet-activating factor receptor
      (PAFR) to invade the respiratory epithelium and that the PAFR is upregulated
      during viral infection, we here used PAFR gene-deficient (PAFR-/-) mice to
      determine the role of this receptor during postinfluenza pneumococcal pneumonia.
      Viral clearance was similar in wild-type and PAFR-/- mice, and influenza virus
      was completely removed from the lungs at the time mice were inoculated with S.
      pneumoniae (day 14 after influenza infection). PAFR-/- mice displayed a
      significantly reduced bacterial outgrowth in their lungs, a diminished
      dissemination of the infection, and a prolonged survival. Pulmonary levels of IL
      10 and KC were significantly lower in PAFR-/- mice, whereas IL-6 and TNF-alpha
      were only trendwise lower. These data indicate that the pneumococcus uses the
      PAFR leading to severe pneumonia in a host previously exposed to influenza A.

PMID- 16100291
TI  - Increased heme catabolism in critically ill patients: correlation among exhaled
      carbon monoxide, arterial carboxyhemoglobin, and serum bilirubin IXalpha
      concentrations.
AB  - It has been reported that exhaled carbon monoxide (CO) concentrations and
      arterial carboxyhemoglobin (CO-Hb) concentration in blood may be increased in
      critically ill patients. However, there was no study that examined correlation
      among amount of CO in exhaled air, CO-Hb concentrations in erythrocytes, and
      bilirubin IXalpha (BR) in serum, i.e., the three major indexes of heme
      catabolism, within the same subject. Here, we examined CO concentrations in
      exhaled air, CO-Hb concentrations in arterial blood, and BR levels in serum in 29
      critically ill patients. Measurements of exhaled CO, arterial CO-Hb, and serum
      total BR have been done in the intensive care unit. As control, exhaled CO
      concentration was also measured in eight healthy volunteers. A median exhaled CO
      concentration was significantly higher in critically ill patients compared with
      control. There was significant correlation between CO and CO-Hb and CO and total
      BR level. We also found CO concentrations correlated with indirect BR but not
      direct BR. Multivariate linear regression analysis for amount of exhaled CO
      concentrations also showed significant correlation with CO-Hb and total BR,
      despite the fact that respiratory variables of study subjects were markedly
      heterogeneous. We found no correlation among exhaled CO, patients' severity, and
      degree of inflammation, but we found a strong trend of a higher exhaled CO
      concentration in survivors than in nonsurvivors. These findings suggest there is
      an increased heme breakdown in critically ill patients and that exhaled CO
      concentration, arterial CO-Hb, and serum total BR concentrations may be useful
      markers in critically ill conditions.

PMID- 16100292
TI  - Extending worldwide clinical pharmacology education through a pricing approach.
AB  - Financial instruments, such as professional membership fees, are part of the
      science and technology policy toolkit for creating an environment conducive to
      developing an international health knowledge network. To minimize a hurdle to
      global knowledge exchange in clinical pharmacology, the American College of
      Clinical Pharmacology reevaluated fees for its international members. Secondary
      market research was conducted on salary data available from US-based
      multinational firms. Salary comparisons for the same position based in the United
      States and in a developing economy were used to generate an index ratio. Applying
      this ratio, a tiered-membership fee structure was constructed for the
      approximately 120 countries where gross national income meets the World Bank
      classification of "developing economy." The index ratio serves as a paradigm for
      structuring fees across a variety of programs. With the implementation of an
      adjusted dues structure, information and networks of colleagues are now more
      accessible to clinical pharmacologists in developing economies.

PMID- 16100293
TI  - The clinical pharmacokinetics of phosphodiesterase-5 inhibitors for erectile
      dysfunction.
AB  - Differences in the clinical pharmacology of the 3 currently available oral
      phosphodiesterase-5 (PDE5) inhibitors, sildenafil, vardenafil, and tadalafil, are
      largely determined by their clinical pharmacokinetics as well as their PDE
      inhibitory activity profile. This review comparatively discusses the major
      characteristics of the pharmacokinetic profile of all 3 PDE5 inhibitors,
      including bioavailability and rate of absorption, Biopharmaceutical
      Classification System categorization, elimination mechanisms, and metabolic
      profile including active metabolites, as well as the drug-drug interaction
      potential and modification of pharmacokinetic properties under selected
      physiologic and pathophysiologic conditions. The review is aimed at providing
      comparative clinical pharmacology data to allow for scientifically rational,
      evidence-based prescribing and dosing decisions regarding the clinical use of
      these medications for the treatment of erectile dysfunction.

PMID- 16100294
TI  - A preliminary assessment of the critical differences between novel oral
      anticoagulants currently in development.
AB  - Chronic anticoagulation represents a clinical conundrum for the health care
      community that balances unquestionable morbidity and mortality benefits against
      interindividual variability, leading to drug interactions, adverse events, and
      thromoembolic events related to underdosing. Despite the growing data regarding
      the appropriate use and dosing of agents used for chronic anticoagulation, use in
      clinical practice remains low, thus leading to a theoretical reduction in the
      risk-to-benefit ratio in the clinical setting relative to that reported in the
      literature. Oral anticoagulants currently in development represent a
      heterogeneous group of compounds that are specific for the final common pathway
      in the coagulation cascade and show indications toward a reduced drug interaction
      profile, reduced interpatient variation in pharmacokinetic parameters, and
      morbidity and mortality benefits that might be similar to currently available
      treatment modalities. This review highlights the critical differences among oral
      anticoagulants in development and places their role in the context of the
      benefits and limitations of currently available anticoagulants.

PMID- 16100295
TI  - Concomitant tacrolimus and micafungin pharmacokinetics in healthy volunteers.
AB  - Tacrolimus is an approved immunosuppressive agent and a known substrate for
      CYP3A. Micafungin is an echinocandin antifungal agent and a mild inhibitor of
      CYP3A metabolism in vitro. The objectives of this study were to evaluate the
      pharmacokinetics of tacrolimus (5 mg oral) and micafungin (100 mg intravenous)
      alone and with concomitant administration (n=26). Tacrolimus area under the
      concentration-time curve was 298+/-135 microg*h/L when tacrolimus was
      administered alone, 305+/-129 microg*h/L (P=.8; confidence interval 89%, 118%)
      when tacrolimus was given with single-dose micafungin, and 282+/-138 microg*h/L
      (P=.4; confidence interval 82%, 107%) when tacrolimus was given with steady-state
      micafungin. Despite the mild inhibition of CYP3A in vitro by micafungin, there
      does not appear to be a drug interaction with tacrolimus and micafungin either
      with single-dose or steady-state micafungin administration.

PMID- 16100296
TI  - The bioequivalence of telithromycin administered orally as crushed tablets versus
      tablets swallowed whole.
AB  - This open-label, randomized, crossover study was conducted to demonstrate
      bioequivalence for telithromycin administered as crushed or whole tablets. Single
      800-mg telithromycin doses (2x400-mg tablets) were administered as crushed
      tablets mixed in 240 mL nutritional supplement drink followed by 120 mL water or
      as whole tablets swallowed with 240 mL water. Plasma telithromycin concentrations
      were measured by liquid chromatography/mass spectrometry; pharmacokinetic
      parameters were determined using noncompartmental methods. Average bioequivalence
      criteria were applied. Thirty-two subjects received telithromycin by both
      methods. The 90% confidence intervals for the geometric mean ratios of maximum
      plasma concentration and area under the plasma concentration-time curve to 24
      hours were within the 0.80 to 1.25 range. Median tmax was 3.00 hours for both
      treatments. Both methods of administration were well tolerated. Crushing
      telithromycin tablets and administering them with a nutritional supplement drink
      is bioequivalent to ingesting whole tablets and could be a viable method of
      administration for patients unable to swallow tablets whole.

PMID- 16100297
TI  - Effect of exenatide on the steady-state pharmacokinetics of digoxin.
AB  - This open-label study investigated the effect of exenatide coadministration on
      the steady-state plasma pharmacokinetics of digoxin. A total of 21 healthy male
      subjects received digoxin (day 1, 0.5 mg twice daily; days 2-12, 0.25 mg once
      daily) and exenatide (days 8-12, 10 microg twice daily). Digoxin plasma and urine
      concentrations were measured on days 7 and 12. Exenatide coadministration did not
      change the overall 24-hour steady-state digoxin exposure (AUCtau,ss) and Cmin,ss
      but caused a 17% decrease in mean plasma digoxin Cmax,ss (1.40 to 1.16 ng/mL) and
      an increase in digoxin tmax,ss (median increase, 2.5 hours). Although the
      decrease in digoxin Cmax,ss was statistically significant, peak concentrations
      were within the therapeutic concentration range in all subjects. Digoxin urinary
      pharmacokinetic parameters were not altered. Gastrointestinal symptoms, the most
      common adverse effects of exenatide, decreased over time. Exenatide
      administration does not cause any changes in digoxin steady-state
      pharmacokinetics that would be expected to have clinical sequelae; thus, dosage
      adjustment does not appear warranted, based on pharmacokinetic considerations.

PMID- 16100298
TI  - QT and QTc interval with standard and supratherapeutic doses of darifenacin, a
      muscarinic M3 selective receptor antagonist for the treatment of overactive
      bladder.
AB  - Prolongation of QT interval on an electrocardiogram is a valuable predictor of a
      drug's ability to cause potentially fatal ventricular tachyarrhythmia (torsades
      de pointes). Darifenacin is a muscarinic M3 selective receptor antagonist
      developed for the treatment of overactive bladder, a debilitating condition that
      is particularly prevalent in the older population. This 7-day, randomized,
      parallel-group study (n=188) measured QT/QTc interval in healthy volunteers
      receiving once-daily darifenacin at steady-state therapeutic (15 mg) and
      supratherapeutic (75 mg) doses, alongside controls receiving placebo or
      moxifloxacin (positive control, 400 mg) once daily. There was no significant
      increase in QTcF interval with darifenacin treatment compared with placebo. Mean
      changes from baseline at pharmacokinetic Tmax versus placebo were -0.4 and -2.2
      milliseconds in the darifenacin 15 mg and 75 mg groups, respectively, compared
      with +11.6 milliseconds in the moxifloxacin group (P<.01). This study
      demonstrates that darifenacin does not prolong QT/QTc interval.

PMID- 16100299
TI  - Acute and chronic effects of vinpocetine on cerebral hemodynamics and
      neuropsychological performance in multi-infarct patients.
AB  - A double-blind, prospective, randomized, placebo-controlled clinical trial was
      carried out to test the acute and long-term hemodynamical and beneficial
      cognitive effects of the vasoactive agent vinpocetine on patients suffering from
      multiple cerebral infarcts by means of functional transcranial Doppler
      examinations and by neuropsychological tests. Twenty-six patients (17 men, 9
      women) with multiple cerebral infarctions, aged between 50 and 83 years (mean
      age+/-SD=63.4+/-9.39 years) were examined, 14 of whom received vinpocetine and 12
      placebo. The functional transcranial Doppler included breath-holding tests,
      finger movement, word fluency, and picture-discrimination tasks. Twenty-five
      patients were assessed by neuropsychological battery. No serious side effect was
      found in the vinpocetine group. The flow velocities were significantly lower in
      the acute phase after breath holding in the vinpocetine group than in the placebo
      group. Three months later, the vinpocetine patients did not show any significant
      worsening in digit span backward test, while the placebo group did. No other
      significant differences in the neuropsychological test could be detected between
      the treatment and the placebo groups. Longer lasting and higher dosage of
      vinpocetine therapy is suggested to prove its potential effect.

PMID- 16100300
TI  - Ibuprofen extrudate, a novel, rapidly dissolving ibuprofen formulation: relative
      bioavailability compared to ibuprofen lysinate and regular ibuprofen, and food
      effect on all formulations.

PMID- 16100301
TI  - Single-dose and steady-state pharmacokinetics of eslicarbazepine acetate (BIA 2
      093) in healthy elderly and young subjects.

PMID- 16100302
TI  - Who cares about health for all in the 21st century?

PMID- 16100303
TI  - A journal for evidence based policies.

PMID- 16100304
TI  - Geographically based approaches can identify environmental causes of disease.

PMID- 16100305
TI  - Job insecurity and its effect on health.

PMID- 16100306
TI  - Flexible employment and health inequalities.

PMID- 16100307
TI  - Incidence of shoulder and neck pain in a working population: effect modification
      between mechanical and psychosocial exposures at work? Results from a one year
      follow up of the Malmo shoulder and neck study cohort.
AB  - STUDY OBJECTIVE: To assess the impact of mechanical exposure and work related
      psychosocial factors on shoulder and neck pain. DESIGN: A prospective cohort
      study. PARTICIPANTS: 4919 randomly chosen, vocationally active men and women ages
      45-65 residing in a Swedish city. Neck and shoulder pain were determined by the
      standardised Nordic questionnaire. Mechanical exposure was assessed by an index
      based on 11 items designed and evaluated for shoulder and neck disorders. Work
      related psychosocial factors were measured by the Karasek and Theorell demand
      control instrument. MAIN RESULTS: High mechanical exposure was associated with
      heightened risk for shoulder and neck pain among men and women during follow up.
      Age adjusted odds ratios (OR) were 2.17 (95% confidence intervals (CI): 1.65,
      2.85) and 1.59 (95% CI: 1.22, 2.06), respectively. In women, job strain (high
      psychological job demands and low job decision latitude) correlated with
      heightened risk (OR = 1.73, 95% CI: 1.29, 2.31). These risk estimates remained
      statistically significant when controlled for high mechanical exposure regarding
      job strain (and vice versa), and for sociodemographic factors. Testing for effect
      modification between high mechanical exposure and job strain showed them acting
      synergistically only in women. CONCLUSION: Job related mechanical exposure in
      both sexes, and psychosocial factors in women, seem independently of each other
      to play a part for development of shoulder and neck pain in vocationally active
      people. The effect of psychosocial factors was more prominent in women, which
      could be the result of biological factors as well as gender issues. These results
      suggest that interventions aiming at reducing the occurrence of shoulder and neck
      pain should include both mechanical and psychosocial factors.

PMID- 16100308
TI  - A brief conceptual tutorial on multilevel analysis in social epidemiology:
      investigating contextual phenomena in different groups of people.
AB  - STUDY OBJECTIVE: (1) To provide a didactic and conceptual (rather than
      mathematical) link between multilevel regression analysis (MLRA) and social
      epidemiological concepts. (2) To develop an epidemiological vision of MLRA
      focused on measures of health variation and clustering of individual health
      status within areas, which is useful to operationalise the notion of "contextual
      phenomenon". The paper shows how to investigate (1) whether there is clustering
      within neighbourhoods, (2) to which extent neighbourhood level differences are
      explained by the individual composition of the neighbourhoods, (3) whether the
      contextual phenomenon differs in magnitude for different groups of people, and
      whether neighbourhood context modifies individual level associations, and (4)
      whether variations in health status are dependent on individual level
      characteristics. DESIGN AND PARTICIPANTS: Simulated data are used on systolic
      blood pressure (SBP), age, body mass index (BMI), and antihypertensive medication
      (AHM) ascribed to 25 000 subjects in 39 neighbourhoods of an imaginary city.
      Rather than assessing neighbourhood variables, the paper concentrated on SBP
      variance between individuals and neighbourhoods as a function of individual BMI.
      RESULTS: The variance partition coefficient (VPC) showed that clustering of SBP
      within neighbourhoods was greater for people with a higher BMI. The composition
      of the neighbourhoods with respect to age, AHM use, and BMI explained about one
      fourth of the neighbourhood differences in SBP. Neighbourhood context modified
      the individual level association between BMI and SBP. Individual level
      differences in SBP within neighbourhoods were larger for people with a higher
      BMI. CONCLUSIONS: Statistical measures of multilevel variations can effectively
      quantify contextual effects in different groups of people, which is a relevant
      issue for understanding health inequalities.

PMID- 16100309
TI  - Binge drinker.

PMID- 16100310
TI  - International cooperation and health. Part 2: making a difference.
AB  - The world is increasingly shaped by powerful global forces, many of which have
      consequences for human health and the social, economic, and environmental factors
      that influence health are increasingly determined at a supranational level. As a
      result, local or national level efforts to influence health determinants can have
      only a limited impact and it is all too easy for the individual public health
      practitioner to feel powerless. Yet while public health practitioners, on their
      own, may indeed be relatively powerless, together they can achieve a great deal.
      Part 2 of this glossary explores some of the strategies that they can use as they
      seek to make a difference.

PMID- 16100311
TI  - Hormone replacement therapy, cancer, controversies, and women's health:
      historical, epidemiological, biological, clinical, and advocacy perspectives.
AB  - Routine acceptance of use of hormone replacement therapy (HRT) was shattered in
      2002 when results of the largest HRT randomised clinical trial, the women's
      health initiative, indicated that long term use of oestrogen plus progestin HRT
      not only was associated with increased risk of cancer but, contrary to
      expectations, did not decrease, and may have increased, risk of cardiovascular
      disease. In June 2004 a group of historians, epidemiologists, biologists,
      clinicians, and women's health advocates met to discuss the scientific and social
      context of and response to these findings. It was found that understanding the
      evolving and contending knowledge on hormones and health requires: (1)
      considering its societal context, including the impact of the pharmaceutical
      industry, the biomedical emphasis on individualised risk and preventive medicine,
      and the gendering of hormones; and (2) asking why, for four decades, since the
      mid-1960s, were millions of women prescribed powerful pharmacological agents
      already demonstrated, three decades earlier, to be carcinogenic? Answering this
      question requires engaging with core issues of accountability, complexity, fear
      of mortality, and the conduct of socially responsible science.

PMID- 16100312
TI  - Measuring paternal discrepancy and its public health consequences.
AB  - Paternal discrepancy (PD) occurs when a child is identified as being biologically
      fathered by someone other than the man who believes he is the father. This paper
      examines published evidence on levels of PD and its public health consequences.
      Rates vary between studies from 0.8% to 30% (median 3.7%, n = 17). Using
      information from genetic and behavioural studies, the article identifies those
      who conceive younger, live in deprivation, are in long term relationships (rather
      than marriages), or in certain cultural groups are at higher risk. Public health
      consequences of PD being exposed include family break up and violence. However,
      leaving PD undiagnosed means cases having incorrect information on their genetics
      and fathers continuing to suspect that children may not be theirs. Increasing
      paternity testing and use of DNA techniques in clinical and judicial procedures
      means more cases of PD will be identified. Given developing roles for
      individual's genetics in decisions made by health services, private services (for
      example, insurance), and even in personal lifestyle decisions, the dearth of
      intelligence on how and when PD should be exposed urgently needs addressing.

PMID- 16100313
TI  - Oil combustion and childhood cancers.
AB  - STUDY OBJECTIVES: To identify specific toxic atmospheric emissions and their
      industrial sources in Great Britain. To link them with each other and with the
      birth addresses of children dying from cancer. To identify specific causal agents
      and sources. DESIGN: Birth and death addresses of children dying from cancer were
      linked to emissions hotspots for specific chemicals: and to related source
      installations. Among those who moved house, distances from each address to the
      nearest hazard were compared. Relative excesses of close-to-hazard birth
      addresses showed high prenatal or early postnatal risks. Relative risks for
      individual and for combined exposures were measured. SETTING AND SUBJECTS:
      Atmospheric emissions hotspots (UK, 2001) published as maps on the internet, were
      converted to coordinates. Industrial sites were identified through trade
      directories and map inspections. Child cancer addresses for 1955-80 births were
      extracted from an earlier inquiry and their postcodes converted to map
      references. MAIN RESULTS: There were excess relative risks (RR) within 0.3 km of
      hotspots for carbon monoxide, PM10 particles, nitrogen oxides, 1,3-butadiene,
      benzene, dioxins, benzo(a)pyrene, and volatiles; and within 1.0 km of bus
      stations, hospitals, heavy transport centres, railways, and oil installations.
      Some excesses were attributable to mutual confounding, but 1,3-butadiene and
      carbon monoxide, mainly derived from engine exhausts, were powerful independent
      predictors. They were strongly reinforced when associated with bus stations,
      hospitals, railways, oil installations, and industrial transport centres; RR =
      12.6 for joint <0.5 km exposure to bus stations and 1,3-butadiene. CONCLUSIONS:
      Childhood cancers are strongly determined by prenatal or early postnatal
      exposures to oil based combustion gases, especially from engine exhausts. 1,3
      butadiene, a known carcinogen, may be directly causal.

PMID- 16100314
TI  - Social inequalities in the impact of flexible employment on different domains of
      psychosocial health.
AB  - STUDY OBJECTIVES: (1) To analyse the impact of flexible employment on mental
      health and job dissatisfaction; and (2) to examine the constraints imposed by
      flexible employment on men's and women's partnership formation and people's
      decision to become parents. For the two objectives the potentially different
      patterns by sex and social class are explored. DESIGN: Cross sectional health
      survey. Multiple logistic regression models separated for sex and social class
      (manual and non-manual workers) and controlling for age were fitted. Four types
      of contractual arrangements have been considered: permanent, fixed term temporary
      contract, non-fixed term temporary contract, and no contract. SETTING: Catalonia
      (a region in the north east of Spain). PARTICIPANTS: Salaried workers interviewed
      in the 2002 Catalonian health survey with no longstanding limiting illness, aged
      16-64 (1474 men and 998 women). MAIN RESULTS: Fixed term temporary contracts were
      not associated with poor mental health status. The impact of other forms of
      flexible employment on mental health depended on the type of contractual
      arrangement, sex, and social class and it was restricted to less privileged
      workers, women, and manual male workers. The impact of flexible employment on
      living arrangements was higher in men. Among both manual and non-manual male
      workers, those with fixed term temporary contracts were less likely to have
      children when married or cohabiting and, additionally, among non-manual male
      workers they also were more likely to remain single (aOR = 2.35; 95%CI = 1.13 to
      4.90). CONCLUSION: Some forms of temporary contracts are related to adverse
      health and psychosocial outcomes with different patterns depending on the outcome
      analysed and on sex and social class. Future research should incorporate
      variables to capture situations of precariousness associated with flexible
      employment.

PMID- 16100315
TI  - Income distribution, public services expenditures, and all cause mortality in US
      States.
AB  - INTRODUCTION: The objective of this paper is to investigate the relation between
      state and local government expenditures on public services and all cause
      mortality in 48 US states in 1987, and determine if the relation between income
      inequality and mortality is conditioned on levels of public services available in
      these jurisdictions. METHODS: Per capita public expenditures and a needs adjusted
      index of public services were examined for their association with age and sex
      specific mortality rates. OLS regression models estimated the contribution of
      public services to mortality, controlling for median income and income
      inequality. RESULTS: Total per capita expenditures on public services were
      significantly associated with all mortality measures, as were expenditures for
      primary and secondary education, higher education, and environment and housing. A
      hypothetical increase of 100 US dollars per capita spent on higher education, for
      example, was associated with 65.6 fewer deaths per 100,000 for working age men
      (p<0.01). The positive relation between income inequality and mortality was
      partly attenuated by controls for public services. DISCUSSION: Public service
      expenditures by state and local governments (especially for education) are
      strongly related to all cause mortality. Only part of the relation between income
      inequality and mortality may be attributable to public service levels.

PMID- 16100316
TI  - Relation between trends in late middle age mortality and trends in old age
      mortality--is there evidence for mortality selection?
AB  - STUDY OBJECTIVE: To test whether mortality selection was a dominant factor in
      determining trends in old age mortality, by empirically studying the existence of
      a negative correlation between trends in late middle age mortality and trends in
      old age mortality among the same cohorts. DESIGN AND METHODS: A cohort approach
      was applied to period data on total and cause specific mortality for Denmark,
      England and Wales, Finland, France, the Netherlands, Norway, and Sweden, in 1950
      1999. The study described and correlated mortality trends for five year
      centralised cohorts from 1895 to 1910 at ages 55-69, with the trends for the same
      cohorts at ages 80-89. The research distinguished between circulatory diseases,
      cancers, and diseases specifically related to old age. MAIN RESULTS: All cause
      mortality changes at ages 80-89 were strongly positively correlated with all
      cause mortality changes at ages 55-69, especially among men, and in all
      countries. Virtually the same correlations were seen between all cause mortality
      changes at ages 80-89 and changes in circulatory disease mortality at ages 55-69.
      Trends in mortality at ages 80-89 from infectious diseases, pneumonia, diabetes
      mellitus, symptoms, or external causes showed no clear negative correlations with
      all cause mortality trends at ages 55-69. CONCLUSIONS: The consistently positive
      correlations seen in this study suggest that trends in old age mortality in north
      western Europe in the late 20th century were determined predominantly by the
      prolonged effects of exposures carried throughout life, and not by mortality
      selection.

PMID- 16100317
TI  - Mortality from heart failure in an English population, 1979-2003: study of death
      certification.
AB  - OBJECTIVE: It is widely held that there will be an epidemic of heart failure in
      Europe and North America as a result of increased survival from myocardial
      infarction and other coronary heart disease. The study objective was to discover
      if the decline in mortality from coronary heart disease has been accompanied by a
      rise in mortality from heart failure in the study population. DESIGN: Analysis of
      database of mortality records including all certified causes of death, not just
      the underlying cause, from 1979-2003. SETTING: Former Oxford NHS Region, England.
      PATIENTS: Data from death certificates of all who died in the population covered.
      MAIN RESULTS: Mortality rates for heart failure fell at very similar rates as
      those from coronary heart disease. In men, the average annual fall in mortality
      from coronary heart disease was -2.7% (95% confidence intervals -2.8 to -2.5) and
      that from heart failure was -2.9% (-3.2 to -2.5). In women, the average annual
      fall in mortality from coronary heart disease was -2.3% (-2.6 to -2.1) and that
      from heart failure was -2.6% (-3.0 to -2.3). CONCLUSIONS: The decline in
      mortality from coronary heart disease has not been accompanied by a rise in
      mortality from heart failure. A future epidemic of heart failure, as a
      consequence of the decline in mortality from coronary heart disease, seems
      unlikely.

PMID- 16100318
TI  - Adverse socioeconomic position across the lifecourse increases coronary heart
      disease risk cumulatively: findings from the British women's heart and health
      study.
AB  - OBJECTIVE: To examine the associations of childhood and adult measurements of
      socioeconomic position with coronary heart disease (CHD) risk. METHODS: Cross
      sectional and prospective analysis of a cohort of 4286 British women who were
      aged 60-79 years at baseline. Among these women there were 694 prevalent cases of
      CHD and 182 new incident cases among 13 217 person years of follow up of women
      who were free of CHD at baseline. RESULTS: All measurements of socioeconomic
      position were associated with increased prevalent and incident CHD in simple age
      adjusted models. There was a cumulative effect, on prevalent and incident CHD, of
      socioeconomic position across the lifecourse. This effect was not fully explained
      by adult CHD risk factors. The adjusted odds ratio of prevalent CHD for each
      additional adverse (out of 10) lifecourse socioeconomic indicator was 1.11 (95%
      confidence interval: 1.06, 1.16). The magnitude of the effect of lifecourse
      socioeconomic position was the same in women who were lifelong non-smokers as in
      those who had been or were smokers. CONCLUSION: Adverse socioeconomic position
      across the lifecourse increases CHD risk cumulatively and this effect is not
      fully explained by adult risk factors. Specifically in this cohort of women
      cigarette smoking does not seem to explain the association between adverse
      lifecourse socioeconomic position and CHD risk.

PMID- 16100319
TI  - Is perceived nervousness and anxiety a predictor of premature mortality and
      severe morbidity? A longitudinal follow up of the Swedish survey of living
      conditions.
AB  - STUDY OBJECTIVE: To find out if people perceiving nervousness, uneasiness, and
      anxiety have excess risks of premature death and severe morbidity. DESIGN,
      SETTING, PARTICIPANTS: Random samples of the Swedish population aged 16-74 years
      in 1980-81, 1988-89, and 1995-96 were followed up for 5 and 10 years with regard
      to deaths and hospital admissions for different causes. Relative risks were
      estimated by Poisson regression, comparing those who reported perceived
      nervousness, uneasiness, and anxiety with those who did not and adjustments were
      made for baseline characteristics as age, education, smoking, and longstanding
      illness. MAIN RESULTS: Perceived nervousness, uneasiness, and anxiety was
      strongly related to subsequent risks of suicide attempt and psychiatric disease.
      Those perceiving severe complaints of anxiety had a relative risk (fully
      adjusted) for suicide attempt of 9.2 (95% CI 3.0 to 28.8) for men and 3.1 (1.4 to
      7.1) for women. Even for less severe complaints, there was a significant, but
      less pronounced excess risk. These negative feelings were also associated with
      later risks for all cause mortality, hospital care, and ischaemic heart disease,
      although to a lesser extent and more strongly among men. Unchanged relative risks
      over time shows no trend in response attitude and perceived anxiety seems to be a
      better predictor of a negative health outcome than self reported longstanding
      illness. CONCLUSIONS: Positive responses to self report survey questions about
      anxiety/nervousness are associated with adverse health outcomes, particularly
      hospital admission for deliberate self harm. This is an alarming signal bearing
      in mind the rapid increase in prevalence of perceived anxiety in the Swedish
      society.

PMID- 16100320
TI  - Socioeconomic gradients in the prevalence of cardiovascular disease in Scotland:
      the roles of composition and context.
AB  - OBJECTIVE: To investigate whether occupational social class and area deprivation
      are independently associated with the prevalence of cardiovascular disease (CVD)
      conditions after adjustment for smoking status. DESIGN: Stratified multistage
      random sample analysed using multilevel logistic regression. PARTICIPANTS: 8804
      adults aged 18-74 at time of interview in 1998-1999, clustered in 312 small
      areas. The outcome considered was a self report of doctor diagnosis of one of a
      number of CVD conditions. The survey also provided information concerning the
      respondent's occupational social class and current smoking status. The Carstairs
      score (based on the 1991 census) was used to describe small area deprivation.
      MAIN RESULTS: The gradient in CVD prevalence across individual social class was
      attenuated and became insignificant when area deprivation was considered. The
      aggregation of individual social class and smoking to the area level increased
      the correlation with disease prevalence at the individual level. CONCLUSIONS:
      Although there is a relation between socioeconomic status and CVD prevalence in
      Scotland, the relation is dominated by area deprivation. When externally
      validated deprivation measures are not available, aggregated individual
      characteristics may show a contextual (as compared with compositional) relation.

PMID- 16100321
TI  - Systematic reviews of health effects of social interventions: 1. Finding the
      evidence: how far should you go?
AB  - STUDY OBJECTIVE: There is little guidance on how to identify useful evidence
      about the health effects of social interventions. The aim of this study was to
      assess the value of different ways of finding this type of information. DESIGN:
      Retrospective analysis of the sources of studies for one systematic review.
      SETTING: Case study of a systematic review of the effectiveness of interventions
      in promoting a population shift from using cars towards walking and cycling. MAIN
      RESULTS: Only four of the 69 relevant studies were found in a "first-line" health
      database such as Medline. About half of all relevant studies were found through
      the specialist Transport database. Nine relevant studies were found through
      purposive internet searches and seven relevant studies were found by chance. The
      unique contribution of experts was not to identify additional studies, but to
      provide more information about those already found in the literature.
      CONCLUSIONS: Most of the evidence needed for this review was not found in studies
      indexed in familiar literature databases. Applying a sensitive search strategy
      across multiple databases and interfaces is very labour intensive. Retrospective
      analysis suggests that a more efficient method might have been to search a few
      key resources, then to ask authors and experts directly for the most robust
      reports of studies identified. However, internet publications and serendipitous
      discoveries did make a significant contribution to the total set of relevant
      evidence. Undertaking a comprehensive search may provide unique evidence and
      insights that would not be obtained using a more focused search.

PMID- 16100322
TI  - Education and mortality: a role for intelligence?

PMID- 16100323
TI  - Acute otitis media after forceps delivery.

PMID- 16100324
TI  - Offspring sex ratios of people exposed to electromagnetic fields.

PMID- 16100325
TI  - What is the relationship between the continuous quality improvement process and
      the research process?

PMID- 16100327
TI  - The scope of practice, standards of practice, and standards of professional
      performance for diabetes educators.

PMID- 16100328
TI  - Choosing and using theories in diabetes education research.
AB  - Diabetes educators use theories all the time, even if they are not aware of it.
      To teach, one must have some assumptions about how people learn and what
      constitutes effective teaching. The purpose of this article is to help diabetes
      educators interested in research and evaluation choose appropriate theories. The
      article will review the 4 purposes of theories, that is, description,
      explanation, prediction, and control, as well as the degree to which a theory has
      been articulated and elaborated. The importance of a theory's personal resonance,
      its explanatory power, and its utility will also be examined. The article will
      also review how to use 1 or more theories at each stage of a research or
      evaluation project.

PMID- 16100329
TI  - Practical management of patients with painful diabetic neuropathy.
AB  - PURPOSE: Painful diabetic neuropathy (PDN) has a significant impact on patients'
      quality of life, affecting sleep, mood, mobility, ability to work, interpersonal
      relationships, overall self-worth, and independence. The purpose of this article
      is to provide diabetes educators with current and essential tools for PDN
      assessment and management. METHODS: Medline and CINAHL database searches
      identified publications on the assessment and treatment of PDN. Identified
      research was evaluated, and information pertinent to diabetes educators was
      summarized. RESULTS: Recent advancements in assessment of neuropathic pain
      include identifying characteristics that distinguish between neuropathic and
      nonneuropathic pain. In the absence of treatment, research demonstrates that
      nerve damage may progress while pain diminishes. Many disease-modifying and
      symptom-management treatment options are available. CONCLUSION: Good glycemic
      control is the first priority for both prevention and management of PDN. However,
      even with good glycemic control, up to 20% of patients will develop PDN. PDN
      recognition and assessment are critical to optimize management. Although several
      treatment modalities are available, few patients obtain complete pain relief.
      Recent advances in understanding the mechanisms underlying neuropathic pain
      should lead to better treatment and patient outcomes. Combination therapy,
      including nonpharmacologic modalities, may be required. Research evaluating the
      efficacy of combination therapy is needed.

PMID- 16100330
TI  - Symptom prevalence and treatments among mexican americans with type 2 diabetes.
AB  - PURPOSE: The purpose of this study was to examine the prevalence of diabetes
      related symptoms among Mexican Americans with type 2 diabetes, their perceptions
      of symptom seriousness, treatments used to self-manage the symptoms, and ratings
      of treatment effectiveness. METHODS: As part of a larger descriptive
      correlational study conducted with 87 Mexican American adults in a southwest
      metropolitan area, data were collected during one-on-one interviews during
      outpatient visits using the Diabetes Symptom Self-care Inventory and analyzed
      with descriptive methods, t tests, and chi(2)s. RESULTS: Participants experienced
      4.9 diabetes-related symptoms in a 30-day period and used a variety of treatments
      to self-manage the symptoms. Many of the self-management strategies were not
      appropriate for the most common causes of the symptoms. Few people tested their
      blood glucose levels in response to symptoms even though most owned glucometers.
      CONCLUSIONS: Most people who experience diabetes symptoms used self-care to treat
      the symptoms, did not verify the cause of the symptom, and perceived their
      treatments as effective. The appropriateness of the treatments used cannot be
      evaluated without knowing the etiology of the symptom for a particular person and
      time. Clinicians must assess symptoms and their treatments to best develop
      effective individualized treatments.

PMID- 16100331
TI  - Soul food light: culturally competent diabetes education.
AB  - PURPOSE: The purpose of this study was to test effects of a culturally competent,
      dietary self-management intervention on physiological outcomes and dietary
      behaviors for African Americans with type 2 diabetes. METHODS: A longitudinal
      experimental study was conducted in rural South Carolina with a sample of 97
      adult African Americans with type 2 diabetes who were randomly assigned to either
      usual care or the intervention. The intervention consisted of 4 weekly classes in
      low-fat dietary strategies, 5 monthly peer-professional group discussions, and
      weekly telephone follow-up. The culturally competent approach reflected the
      ethnic beliefs, values, customs, food preferences, language, learning methods,
      and health care practices of southern African Americans. RESULTS: Body mass index
      and dietary fat behaviors were significantly lowered in the experimental group.
      At 6 months, weight decreased 1.8 kg (4 lb) for the experimental group and
      increased 1.9 kg (4.2 lb) for the control group, a net difference of 3.7 kg (8.2
      lb). The experimental group reduced high-fat dietary habits to moderate while
      high-fat dietary habits of the control group remained essentially unchanged. A
      trend in reduction of A1C and lipids was observed. CONCLUSIONS: Results suggest
      the effectiveness of a culturally competent dietary self-management intervention
      in improving health outcomes for southern African Americans, especially those at
      risk due to high-fat diets and body mass index >or= 35 kg/mm(2). Given the
      burgeoning problem of obesity in South Carolina and the nation, the time has come
      to focus on aggressive weight management. Diabetes educators are in pivotal
      positions to assume leadership in achieving this goal for vulnerable, rural
      populations.

PMID- 16100332
TI  - Clinical inertia contributes to poor diabetes control in a primary care setting.
AB  - PURPOSE: The purpose of this study was to determine whether "clinical inertia"
      inadequate intensification of therapy by the provider-could contribute to high
      A1C levels in patients with type 2 diabetes managed in a primary care site.
      METHODS: In a prospective observational study, management was compared in the
      Medical Clinic, a primary care site supervised by general internal medicine
      faculty, and the Diabetes Clinic, a specialty site supervised by
      endocrinologists. These municipal hospital clinics serve a common population that
      is largely African American, poor, and uninsured. RESULTS: Four hundred thirty
      eight African American patients in the Medical Clinic and 2157 in the Diabetes
      Clinic were similar in average age, diabetes duration, body mass index, and
      gender, but A1C averaged 8.6% in the Medical Clinic versus 7.7% in the Diabetes
      Clinic (P < .0001). Use of pharmacotherapy was less intensive in the Medical
      Clinic (less use of insulin), and when patients had elevated glucose levels
      during clinic visits, therapy was less than half as likely to be advanced in the
      Medical Clinic compared to the Diabetes Clinic (P < .0001). Intensification rates
      were lower in the Medical Clinic regardless of type of therapy (P < .0001), and
      intensification of therapy was independently associated with improvement in A1C
      (P < .001). CONCLUSIONS: Medical Clinic patients had worse glycemic control, were
      less likely to be treated with insulin, and were less likely to have their
      therapy intensified if glucose levels were elevated. To improve diabetes
      management and glycemic control nationwide, physicians in training and
      generalists must learn to overcome clinical inertia, to intensify therapy when
      appropriate, and to use insulin when clinically indicated.

PMID- 16100333
TI  - Disordered eating behaviors in youth with type 1 diabetes.
AB  - Eating disorders are a significant health problem for many adolescents and are
      described as occurring along a spectrum of symptoms including disordered eating
      behaviors and clinical eating disorders. Poor self-esteem and body image, intense
      fear of gaining weight or refusal to maintain weight, and purging unwanted
      calories are clinical features of some eating disorders. Type 1 diabetes is a
      chronic illness with marked insulin deficiency. Chronic hyperglycemia creates a
      state of glucosuria with subsequent weight loss. Diabetes treatment focuses on
      intensive daily management of blood glucose by balancing insulin, food intake,
      and physical activity. Insulin omission offers an easy method for the purging of
      unwanted calories. The combination of these 2 illnesses is potentially deadly and
      also leads to an increased risk of poor diabetes outcomes. This includes poor
      metabolic control (measured by elevated hemoglobin A1C), increased risk of
      diabetic ketoacidosis, and microvascular complications such as retinopathy and
      nephropathy. Diabetes clinicians should be aware of the potential warning signs
      in an adolescent with diabetes as well as assessment and treatment options for
      eating disorders with concomitant type 1 diabetes. This article reviews the
      available data on the prevalence, screening tools, assessment guidelines, and
      treatment options for eating disorders in youth with type 1 diabetes.

PMID- 16100334
TI  - Case study: contrasting challenges of insulin pump therapy in a toddler and
      adolescent with type 1 diabetes.
AB  - PURPOSE: To describe the challenges and outcomes of continuous subcutaneous
      insulin infusion (CSII) pump therapy in a toddler and adolescent with type 1
      diabetes. Insight into patient-family aspects motivating pump use is provided.
      METHODS: Two cases treated at the Pediatric Diabetes Clinic at Yale University.
      RESULTS: Upon parental request, CSII was initiated to improve glycemic control in
      a 4-year-old boy (case 1) with unpredictable food intake. During 68 months of
      CSII therapy, hemoglobin A1C levels averaged 6.3% +/- 0.6%. Severe hypoglycemic
      episodes ceased 36 months ago, and occasional postprandial hyperglycemia during
      early school years was corrected with school nurses' reminders about premeal
      insulin bolus doses. Currently 9.5 years old, he independently manages all his
      insulin injections with parental assistance only to change the catheter site.
      Case 2 is a girl who was nearly 12 years of age when diagnosed with type 1
      diabetes. Initially managed with daily injections, hypoglycemic episodes were
      interfering with her physically active lifestyle. At age 13 years, she elected
      CSII therapy, and glycemic control improved. Temporarily erratic in the immediate
      period pre- and postmenarche, metabolic control has since stabilized. At 15 years
      old, she successfully manages her diabetes independently. CONCLUSIONS: To
      optimize glycemic control, CSII can be initiated and used effectively, both in
      children of all ages and in adolescents with type 1 diabetes. CSII may be ideal
      therapy for toddlers, with no apparent lower age boundary for initiating CSII;
      however, the parenting challenges and requirements for supportive education
      differ between toddlers and adolescents. When disease and pump management are
      appropriately individualized, CSII therapy can help children with diabetes
      achieve and sustain glycemic control. Lifestyle flexibility, quality-of-life
      improvement, and independence can thus begin early in childhood and be maintained
      throughout young adulthood.

PMID- 16100335
TI  - Monomethyl histone H3 lysine 4 as an epigenetic mark for silenced euchromatin in
      Chlamydomonas.
AB  - Histone Lys methylation plays an important role in determining chromatin states
      and is mostly catalyzed by SET domain-containing proteins. The outcome,
      transcriptional repression or activation, depends on the methylated histone
      residue, the degree of methylation, and the chromatin context. Dimethylation or
      trimethylation of histone H3 Lys 4 (H3K4me2 or H3K4me3) has been correlated with
      transcriptionally competent/active genes. However, H3K4 methylation has also been
      implicated in gene silencing. This dualistic nature of the H3K4 methyl mark has
      thus far remained unresolved. In the green alga Chlamydomonas reinhardtii,
      Mut11p, related to a subunit of trithorax-like methyltransferase complexes, is
      required for transcriptional silencing. Here, we show that Mut11p interacts with
      conserved components of H3K4 methyltransferase machineries, and an affinity
      purified Mut11p complex(es) methylates histones H3, H2A, and H4. Moreover, a
      Mut11 mutant showed global loss of monomethylated H3K4 (H3K4me1) and an increase
      in dimethylated H3K4. By chromatin immunoprecipitation analysis, this strain also
      displayed substantial reduction in H3K4me1 and enrichment in H3K4me2 associated
      with transcriptionally derepressed genes, transgenes, and retrotransposons. RNA
      interference-mediated suppression of Set1, encoding an H3K4 methyltransferase,
      induced similar phenotypes, but of lower magnitude, and no detectable increase in
      H3K4me2. Together, our results suggest functional differentiation between
      dimethyl H3K4 and monomethyl H3K4, with the latter operating as an epigenetic
      mark for repressed euchromatin.

PMID- 16100336
TI  - Rab11 GTPase-regulated membrane trafficking is crucial for tip-focused pollen
      tube growth in tobacco.
AB  - Pollen tube growth is a polarized growth process whereby the tip-growing tubes
      elongate within the female reproductive tissues to deliver sperm cells to the
      ovules for fertilization. Efficient and regulated membrane trafficking activity
      incorporates membrane and deposits cell wall molecules at the tube apex and is
      believed to underlie rapid and focused growth at the pollen tube tip. Rab
      GTPases, key regulators of membrane trafficking, are candidates for important
      roles in regulating pollen tube growth. We show that a green fluorescent protein
      tagged Nicotiana tabacum pollen-expressed Rab11b is localized predominantly to an
      inverted cone-shaped region in the pollen tube tip that is almost exclusively
      occupied by transport vesicles. Altering Rab11 activity by expressing either a
      constitutive active or a dominant negative variant of Rab11b in pollen resulted
      in reduced tube growth rate, meandering pollen tubes, and reduced male fertility.
      These mutant GTPases also inhibited targeting of exocytic and recycled vesicles
      to the pollen tube inverted cone region and compromised the delivery of secretory
      and cell wall proteins to the extracellular matrix. Properly regulated Rab11
      GTPase activity is therefore essential for tip-focused membrane trafficking and
      growth at the pollen tube apex and is pivotal to reproductive success.

PMID- 16100337
TI  - The TIP GROWTH DEFECTIVE1 S-acyl transferase regulates plant cell growth in
      Arabidopsis.
AB  - TIP GROWTH DEFECTIVE1 (TIP1) of Arabidopsis thaliana affects cell growth
      throughout the plant and has a particularly strong effect on root hair growth. We
      have identified TIP1 by map-based cloning and complementation of the mutant
      phenotype. TIP1 encodes an ankyrin repeat protein with a DHHC Cys-rich domain
      that is expressed in roots, leaves, inflorescence stems, and floral tissue. Two
      homologues of TIP1 in yeast (Saccharomyces cerevisiae) and human (Homo sapiens)
      have been shown to have S-acyl transferase (also known as palmitoyl transferase)
      activity. S-acylation is a reversible hydrophobic protein modification that
      offers swift, flexible control of protein hydrophobicity and affects protein
      association with membranes, signal transduction, and vesicle trafficking within
      cells. We show that TIP1 binds the acyl group palmitate, that it can rescue the
      morphological, temperature sensitivity, and yeast casein kinase2 localization
      defects of the yeast S-acyl transferase mutant akr1Delta, and that inhibition of
      acylation in wild-type Arabidopsis roots reproduces the Tip1- mutant phenotype.
      Our results demonstrate that S-acylation is essential for normal plant cell
      growth and identify a plant S-acyl transferase, an essential research tool if we
      are to understand how this important, reversible lipid modification operates in
      plant cells.

PMID- 16100338
TI  - Great expectations of modern RA treatment.

PMID- 16100339
TI  - Cyclophosphamide reduces neutrophilic alveolitis in patients with scleroderma
      lung disease: a retrospective analysis of serial bronchoalveolar lavage
      investigations.
AB  - OBJECTIVES: To determine whether cyclophosphamide is beneficial for patients with
      scleroderma lung disease (SLD). METHODS: The effect of 6 months' treatment with
      intravenous cyclophosphamide on the functional capacity of patients, lung
      function tests, high resolution computed tomography of the lungs, and cytology of
      bronchoalveolar lavage was evaluated in 21 patients with SLD. RESULTS: The
      treatment was well tolerated and all patients completed 6 months' treatment.
      Intravenous cyclophosphamide stabilised or improved the patients' functional
      status and lung function tests. The extent of the lungs affected remained
      unchanged, as assessed with HRCT of the lungs. Patients with SLD and neutrophilic
      alveolitis (NA) showed greater improvement than patients with normal levels of
      granulocytes in the bronchoalveolar lavage fluid (BALF). Significant reduction of
      neutrophils was also seen in the patients with SLD and NA, whereas no significant
      change was seen in the level of granulocytes in patients with SLD and an
      initially normal percentage of granulocytes. CONCLUSIONS: Previous reports that
      patients with SLD with increased levels of granulocytes in BALF are more likely
      to benefit from treatment with intravenous cyclophosphamide are confirmed.
      Additionally, clinical improvement in this group of patients is accompanied by a
      significant decrease in the percentage of granulocytes in BALF.

PMID- 16100340
TI  - Further evidence that a cartilage-pannus junction synovitis predilection is not a
      specific feature of rheumatoid arthritis.
AB  - BACKGROUND: Qualitative differences in synovitis between the cartilage-pannus
      junction (CPJ) region and the adjoining suprapatellar pouch (SPP) have been
      reported in rheumatoid arthritis and the spondyloarthropathies. OBJECTIVE: To
      determine if the distribution of synovitis is the same in osteoarthritis (OA)
      using sensitive measures of inflammation derived from dynamic, contrast enhanced
      magnetic resonance imaging (DEMRI). METHODS: 20 subjects with established OA of
      the knee were recruited. Conventional MR images together with the DEMRI
      measurements were obtained. Areas of synovitis at the CPJ region and at a distant
      site in the SPP were calculated; differences in CPJ and SPP synovitis were
      determined using DEMRI parameters: the initial rate of contrast enhancement (IRE)
      and maximal enhancement (ME). RESULTS: The area of synovitis was significantly
      greater adjacent to the CPJ than in the SPP. IRE and ME measures were greater at
      the CPJ than the SPP. CONCLUSIONS: The magnitude of synovitis at the CPJ is not
      disease-specific and applies across the spectrum of degenerative disease as well
      as inflammatory diseases.

PMID- 16100341
TI  - Potential relationship between herpes viruses and rheumatoid arthritis: analysis
      with quantitative real time polymerase chain reaction.
AB  - OBJECTIVE: To determine whether the human herpes viruses, cytomegalovirus (CMV),
      Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6), are detectable in
      serum and peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid
      arthritis (RA). METHODS: 133 PBMC samples (61 RA, 72 healthy donors) and 136
      serum samples (59 RA, 77 healthy donors) were analysed by quantitative real time
      polymerase chain reaction for DNA prevalence and viral load of HHV-6, EBV, and
      CMV. RESULTS: For PBMC samples significant differences were found for EBV in DNA
      prevalence (56% in RA v 33% in controls, p = 0.009) and viral load (copies/microg
      DNA 0-592.3 for RA v 0-40.4 for controls, p = 0.001). For serum samples a
      significant difference was found for HHV-6 DNA prevalence (10% in RA v 0% in
      controls, p = 0.006) and viral load (copies/microg DNA 0-529.1 for RA v 0 for
      controls, p = 0.007). CONCLUSIONS: Herpes viruses may have a role in RA, although
      alternative explanations are possible: (a) defects in cellular immunity in
      patients with RA may result in a relatively high viral load; (b) patients with RA
      may be more prone to infection/reactivation. The usefulness of monitoring the DNA
      viral load in patients with RA is questioned by these data.

PMID- 16100342
TI  - Attenuated response to purified protein derivative in patients with rheumatoid
      arthritis: study in a population with a high prevalence of tuberculosis.
AB  - BACKGROUND: The purified protein derivative (PPD) skin test is the only widely
      used method which detects latent tuberculosis infection (LTBI) and is dependent
      on a normal T cell function. In rheumatoid arthritis (RA) the T cell function is
      altered, which may result in an inability to develop an adequate PPD reaction.
      OBJECTIVES: To evaluate the response to PPD in patients with RA and to compare it
      with that of control subjects. METHODS: 112 patients with RA and 96 healthy
      controls were studied. PPD 5 U was applied using the Mantoux method, and skin
      reaction was measured at 72 hours. The reaction was considered negative for PPD
      <5 mm. RESULTS: There were no significant differences in age, sex, history of
      bacille Calmette-Guerin vaccination, or tuberculosis contact between the two
      groups. The median size of the PPD induration in the patients with RA was
      significantly less than that in the control group (4.5 v 11.5 mm, p<0.01). 79
      (70.6%) patients with RA compared with 25 (26%) of the control group had a
      negative reaction to PPD (p<0.01), a response not influenced by disease activity
      or duration of disease in the patients with RA. CONCLUSION: A PPD skin test is
      not an appropriate test for recognising LTBI in patients with RA in our
      population.

PMID- 16100343
TI  - Raised plasma levels of asymmetric dimethylarginine are associated with
      cardiovascular events, disease activity, and organ damage in patients with
      systemic lupus erythematosus.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide
      inhibitor and a new independent risk factor for endothelial dysfunction and
      cardiovascular disease. OBJECTIVE: To investigate the relationship between plasma
      ADMA levels and cardiovascular events (CVEs) and disease characteristics in
      patients with systemic lupus erythematosus (SLE). METHODS: Demographic and
      clinical data were collected and plasma ADMA levels were measured in 107 patients
      with SLE. A modified organ damage index was calculated as defined by the Systemic
      Lupus International Collaborating Clinics/American College of Rheumatology Damage
      Index (SDI), excluding CVE as an item. RESULTS: Cardiovascular disease, defined
      as > or =1 previous arterial CVE, was recorded in 16/107 (15%) patients with SLE
      and increased across tertiles of ADMA levels (p = 0.023 for trend). Mean plasma
      ADMA levels were significantly higher in patients with SLE with a history of CVEs
      than in patients without a CVE history (p = 0.018). In multiple regression
      analysis a high SLEDAI score, high modified SDI, high titre of anti-dsDNA
      antibodies, and low serum HDL were significantly associated with high plasma ADMA
      levels. CONCLUSION: In patients with SLE, plasma ADMA levels are significantly
      associated with CVEs, measures of disease activity, and organ damage,
      independently of an unfavourable lipid profile.

PMID- 16100344
TI  - Lupus thrombocytopenia: clinical implications and prognostic significance.
AB  - OBJECTIVES: To clarify clinical manifestations, association with disease
      activity, and prognostic impact of thrombocytopenia using simple and reliable
      indices. METHODS: 632 patients were reviewed retrospectively. Fifty patients with
      thrombocytopenia were included as cases and matched with 100 control patients.
      Clinical manifestations at first thrombocytopenic episode were recorded.
      Classification criteria at diagnosis, basic immunological profiles, disease
      activity (ECLAM), and end organ damage (SLICC) were recorded. RESULTS: 29/50
      (58%) had thrombocytopenia at diagnosis of lupus. Haemorrhagic manifestations
      were associated with the degree of thrombocytopenia (p<0.001). Anticardiolipin
      antibodies were not related to the degree of thrombocytopenia or the severity of
      haemorrhagic manifestations. Megakaryocytes were normal or increased in 26/28
      (93%) bone marrow specimens, indicating peripheral platelet destruction. Patients
      with high disease activity were more thrombocytopenic than controls (OR = 2.61,
      95% CI 1.13 to 5.96, p = 0.009). Patients with low C3 or CH50 were more likely to
      be thrombocytopenic (OR = 2.36, 95% CI 1.05 to 5.26, p = 0.029). Median SLICC for
      lupus patients with thrombocytopenia was 2 (range 0-11) compared with 1 (range 0
      12) for controls (p<0.001). No deaths occurred during thrombocytopenic episodes.
      CONCLUSIONS: Thrombocytopenia is not directly associated with end organ damage
      and mortality, but defines a subgroup of patients with higher morbidity and is
      thus a major complication of systemic lupus erythematosus, affecting overall
      prognosis.

PMID- 16100345
TI  - Weight loss with purpura and pain at the distal femora.

PMID- 16100346
TI  - Long term infliximab treatment for severe psoriatic arthritis: evidence of
      sustained clinical and radiographic response.

PMID- 16100347
TI  - Topical tacrolimus treatment in a patient with dermatomyositis.

PMID- 16100348
TI  - Surgery in patients receiving anti-tumour necrosis factor alpha treatment in
      rheumatoid arthritis: an observational study on 50 surgical procedures.

PMID- 16100349
TI  - Increase in methotrexate dose in patients with rheumatoid arthritis who have an
      inadequate response to infliximab.

PMID- 16100350
TI  - The T348M mutated form of cryopyrin is associated with defective
      lipopolysaccharide-induced interleukin 10 production in CINCA syndrome.

PMID- 16100351
TI  - Churg-Strauss vasculitis syndrome and leukotriene receptor antagonists.

PMID- 16100352
TI  - A major subset of patients with ankylosing spondylitis followed up in tertiary
      clinical care require anti-tumour necrosis factor alpha biological treatments
      according to the current guidelines.

PMID- 16100353
TI  - Colchicine responsive periodic fever syndrome associated with pyrin I591T.

PMID- 16100354
TI  - Whale of a tale.

PMID- 16100355
TI  - Pagetic hydrocephalus treated with zoledronate.

PMID- 16100356
TI  - Oral sildenafil for the treatment of Raynaud's phenomenon and digital ulcers
      secondary to systemic sclerosis.

PMID- 16100357
TI  - Other dangers of herbal remedies in rheumatology.

PMID- 16100358
TI  - The root tip and accelerating region suppress elongation of the decelerating
      region without any effects on cell turgor in primary roots of maize under water
      stress.
AB  - To identify the region in which a root perceives a decrease in the ambient water
      potential and changes its elongation rate, we applied two agar blocks (1 x 1 x 1
      mm(3)) with low water potential bilaterally to primary roots of maize (Zea mays)
      at various positions along the root. When agar blocks with a water potential of 
      1.60 MPa (-1.60-MPa blocks) or lower were attached to a root tip, the rate of
      elongation decreased. This decrease did not result from any changes in the water
      status of elongating cells and was not reversed when the -1.60-MPa blocks were
      replaced by -0.03-MPa blocks. The rate decreased slightly and was unaffected,
      respectively, when -1.60-MPa blocks were applied to the so-called decelerating
      region of the elongating zone and the mature region. However, the rate decreased
      markedly and did not recover for several hours at least when such blocks were
      attached to the accelerating region. In this case, the turgor pressure of the
      elongating cells decreased immediately after the application of the blocks and
      recovered thereafter. The decrease in elongation rate caused by -1.60-MPa blocks
      applied to the root tip was unaffected by additional -0.03-MPa blocks applied to
      the accelerating region and vice versa. We concluded that a significant reduction
      in root growth could be induced by water stress at the root tip, as well as in
      the accelerating region of the elongating zone, and that transmission of some
      signal from these regions to the decelerating region might contribute to the
      suppression of cell elongation in the elongation region.

PMID- 16100359
TI  - Do xylem fibers affect vessel cavitation resistance?
AB  - Possible mechanical and hydraulic costs to increased cavitation resistance were
      examined among six co-occurring species of chaparral shrubs in southern
      California. We measured cavitation resistance (xylem pressure at 50% loss of
      hydraulic conductivity), seasonal low pressure potential (P(min)), xylem
      conductive efficiency (specific conductivity), mechanical strength of stems
      (modulus of elasticity and modulus of rupture), and xylem density. At the
      cellular level, we measured vessel and fiber wall thickness and lumen diameter,
      transverse fiber wall and total lumen area, and estimated vessel implosion
      resistance using (t/b)(h)(2), where t is the thickness of adjoining vessel walls
      and b is the vessel lumen diameter. Increased cavitation resistance was
      correlated with increased mechanical strength (r(2) = 0.74 and 0.76 for modulus
      of elasticity and modulus of rupture, respectively), xylem density (r(2) = 0.88),
      and P(min) (r(2) = 0.96). In contrast, cavitation resistance and P(min) were not
      correlated with decreased specific conductivity, suggesting no tradeoff between
      these traits. At the cellular level, increased cavitation resistance was
      correlated with increased (t/b)(h)(2) (r(2) = 0.95), increased transverse fiber
      wall area (r(2) = 0.89), and decreased fiber lumen area (r(2) = 0.76). To our
      knowledge, the correlation between cavitation resistance and fiber wall area has
      not been shown previously and suggests a mechanical role for fibers in cavitation
      resistance. Fiber efficacy in prevention of vessel implosion, defined as inward
      bending or collapse of vessels, is discussed.

PMID- 16100367
TI  - Retrospective study of the survival of cats with acquired chronic renal
      insufficiency offered different commercial diets.
AB  - A retrospective study was carried out on the efficacy of seven commercial diets
      designed to be fed to cats with chronic renal failure. The median survival time
      of 175 cats that received conventional diets was seven months, whereas the median
      survival time of 146 cats given one of the seven diets was 16 months. The cats on
      the most effective of the diets had a median survival time of 23 months and those
      on the least effective diet had a median survival time of 12 months. The
      composition of the seven diets was comparable, except that the most effective
      diet had a particularly high content of eicosapentaenoic acid.

PMID- 16100368
TI  - Estimating the financial losses due to bovine fasciolosis in Switzerland.
AB  - In dairy cattle in Switzerland, the prevalence of infection with Fasciola
      hepatica is over 16 per cent. Previous studies have suggested that even
      subclinical infections with liver fluke may induce significant reductions in the
      performance of cattle. The financial losses attributable to F hepatica were
      estimated using a simple spreadsheet model to sum the individual losses that have
      been suggested in the literature. Because there is substantial variability in
      these production losses, Monte Carlo sampling techniques were used to model this
      variability. Each cost item and each data item related to the prevalence of F
      hepatica was assigned a mathematical distribution which took account of the
      variability of the experimental data and/or the sample size of the data. A total
      of 10,000 simulations were undertaken, with each item randomly varied through its
      mathematical distribution on each simulation. The results suggest that the median
      financial loss due to bovine fasciolosis in Switzerland is approximately 52
      million, with probable 95 per cent confidence limits ranging from 22 million to
      92 million per annum, which represents a median loss of 299 per infected animal.
      Most of the losses arise from reduced milk yield and reduced fertility, and
      smaller losses are due to reduced meat production and the condemnation of livers.

PMID- 16100369
TI  - Antimicrobial resistance in Escherichia coli isolated from bitches with pyometra
      and from urine samples from other dogs.
AB  - To assess whether the rates of antimicrobial susceptibility in bacteria isolated
      from the urine of dogs with urinary tract infections are similar to those of
      bacteria isolated from bitches with pyometra, the antimicrobial resistance of
      Escherichia coli isolated from the two groups were determined and compared. The
      samples were collected in Sweden between April 2002 and March 2003, and potential
      changes over time were assessed by comparing the results with corresponding data
      from 1991 to 1993. Among 80 isolates of E coli from cases of pyometra, the
      proportions that were resistant to the antimicrobials used in canine practice
      were generally low (ampicillin 10 per cent, enrofloxacin 4 per cent, gentamicin 0
      per cent, streptomycin 5 per cent, sulfamethoxazole 8 per cent, tetracycline 4
      per cent and trimethoprim 2 per cent) and similar to the proportions reported
      previously. Significantly lower proportions of resistance were recorded among the
      pyometra isolates than among 92 isolates from urine samples submitted by animal
      hospitals to ampicillin (P=0.04), streptomycin (P=0.002) and tetracycline
      (P=0.03), but there were no differences between the pyometra isolates and 113
      isolates from urine samples submitted by animal clinics.

PMID- 16100370
TI  - Carpal collateral ligament desmopathy in three horses.
AB  - The radiographic and ultrasonographic findings in three horses with severe damage
      to the collateral ligaments of the carpus, associated with degenerative joint
      disease, are described. The horses remained lame despite prolonged rest and
      medical management, primarily because of the progression of the joint disease.
      Ultrasonography was found to be an accurate method for diagnosing the injury to
      the ligaments and is recommended as part of a routine examination in suspected
      carpal injuries.

PMID- 16100371
TI  - Association between clinical hypocalcaemia and postpartum endometritis.

PMID- 16100372
TI  - Anal adenomatous polyps in a crossbred beef cow.

PMID- 16100373
TI  - Natural transmission of BSE between sheep within an experimental flock.

PMID- 16100374
TI  - Review of the Veterinary Surgeons Act.

PMID- 16100375
TI  - Tackling future disease outbreaks.

PMID- 16100376
TI  - Primary cutaneous listeriosis in a veterinarian.

PMID- 16100377
TI  - Review of the Veterinary Surgeons Act.

PMID- 16100378
TI  - Synergistic defect in 60S ribosomal subunit assembly caused by a mutation of
      Rrs1p, a ribosomal protein L11-binding protein, and 3'-extension of 5S rRNA in
      Saccharomyces cerevisiae.
AB  - Rrs1p, a ribosomal protein L11-binding protein, has an essential role in
      biogenesis of 60S ribosomal subunits. We obtained conditionally synthetic lethal
      allele with the rrs1-5 mutation and determined that the mutation is in REX1,
      which encodes an exonuclease. The highly conserved leucine at 305 was substituted
      with tryptophan in rex1-1. The rex1-1 allele resulted in 3'-extended 5S rRNA.
      Polysome analysis revealed that rex1-1 and rrs1-5 caused a synergistic defect in
      the assembly of 60S ribosomal subunits. In vivo and in vitro binding assays
      indicate that Rrs1p interacts with the ribosomal protein L5-5S rRNA complex. The
      rrs1-5 mutation weakens the interaction between Rrs1p with both L5 and L11. These
      data suggest that the assembly of L5-5S rRNA on 60S ribosomal subunits
      coordinates with assembly of L11 via Rrs1p.

PMID- 16100379
TI  - Using multiple alignments to improve seeded local alignment algorithms.
AB  - Multiple alignments among genomes are becoming increasingly prevalent. This trend
      motivates the development of tools for efficient homology search between a query
      sequence and a database of multiple alignments. In this paper, we present an
      algorithm that uses the information implicit in a multiple alignment to
      dynamically build an index that is weighted most heavily towards the promising
      regions of the multiple alignment. We have implemented Typhon, a local alignment
      tool that incorporates our indexing algorithm, which our test results show to be
      more sensitive than algorithms that index only a sequence. This suggests that
      when applied on a whole-genome scale, Typhon should provide improved homology
      searches in time comparable to existing algorithms.

PMID- 16100380
TI  - Interplay between GCN2 and GCN4 expression, translation elongation factor 1
      mutations and translational fidelity in yeast.
AB  - Genetic screens in Saccharomyces cerevisiae have identified the roles of ribosome
      components, tRNAs and translation factors in translational fidelity. These
      screens rely on the suppression of altered start codons, nonsense codons or
      frameshift mutations in genes involved in amino acid or nucleotide metabolism.
      Many of these genes are regulated by the General Amino Acid Control (GAAC)
      pathway. Upon amino acid starvation, the kinase GCN2 induces the GAAC cascade via
      increased translation of the transcriptional activator GCN4 controlled by
      upstream open reading frames (uORFs). Overexpression of the GCN2 or GCN4 genes
      enhances the sensitivity of translation fidelity assays that utilize genes
      regulated by GCN4, such as the suppression of a +1 insertion by S.cerevisiae
      translation elongation factor 1A (eEF1A) mutants. Paromomycin and the prion
      [PSI+], which reduce translational fidelity, do not increase GCN4 expression to
      induce the suppression phenotype and in fact reduce derepression. eEF1A mutations
      that reduce translation, however, reduce expression of GCN4 under non-starvation
      conditions. These eEF1A mutants also reduce HIS4 mRNA expression. Taken together,
      this system improves in vivo strategies for the analysis of translational
      fidelity and further provides new information on the interplay among translation
      fidelity, altered elongation and translational control via uORFs.

PMID- 16100381
TI  - A peripheral element assembles the compact core structure essential for group I
      intron self-splicing.
AB  - The presence of non-conserved peripheral elements in all naturally occurring
      group I introns underline their importance in ensuring the natural intron
      function. Recently, we reported that some peripheral elements are conserved in
      group I introns of IE subgroup. Using self-splicing activity as a readout, our
      initial screening revealed that one such conserved peripheral elements, P2.1, is
      mainly required to fold the catalytically active structure of the Candida
      ribozyme, an IE intron. Unexpectedly, the essential function of P2.1 resides in a
      sequence-conserved short stem of P2.1 but not in a long-range interaction
      associated with the loop of P2.1 that stabilizes the ribozyme structure. The P2.1
      stem is indispensable in folding the compact ribozyme core, most probably by
      forming a triple helical interaction with two core helices, P3 and P6.
      Surprisingly, although the ribozyme lacking the P2.1 stem renders a loosely
      folded core and the loss of self-splicing activity requires two consecutive
      transesterifications, the mutant ribozyme efficiently catalyzes the first
      transesterification reaction. These results suggest that the intron self-splicing
      demands much more ordered structure than does one independent
      transesterification, highlighting that the universally present peripheral
      elements achieve their functional importance by enabling the highly ordered
      structure through diverse tertiary interactions.

PMID- 16100382
TI  - Identification of RNA editing sites in the SNP database.
AB  - The relationship between human inherited genomic variations and phenotypic
      differences has been the focus of much research effort in recent years. These
      studies benefit from millions of single-nucleotide polymorphism (SNP) records
      available in public databases, such as dbSNP. The importance of identifying false
      dbSNP records increases with the growing role played by SNPs in linkage analysis
      for disease traits. In particular, the emerging understanding of the abundance of
      DNA and RNA editing calls for a careful distinction between inherited SNPs and
      somatic DNA and RNA modifications. In order to demonstrate that some of the SNP
      database records are actually somatic modification, we focus on one type of these
      modifications, namely A-to-I RNA editing, and present evidence for hundreds of
      dbSNP records that are actually editing sites. We provide a list of 102 RNA
      editing sites previously annotated in dbSNP database as SNPs, and experimentally
      validate seven of these. Interestingly, we show how dbSNP can serve as a starting
      point to look for new editing sites. Our results, for this particular type of RNA
      editing, demonstrate the need for a careful analysis of SNP databases in light of
      the increasing recognition of the significance of somatic sequence modifications.

PMID- 16100383
TI  - Clinical and investigational considerations for the use of IGIV therapy.
AB  - PURPOSE: Clinical uses of immunoglobulin intravenous (IGIV) therapy for a number
      of autoimmune and inflammatory diseases are discussed, as well as the probable
      mechanisms by which IGIV exerts its immunoregulatory and antiinflammatory
      actions. Case studies are also presented to examine practical considerations in
      the selection of IGIV products for patients at risk for adverse events. SUMMARY:
      At present, the Food and Drug Administration has approved IGIV for use in six
      conditions, including replacement therapy for patients with antibody-deficiency
      disease, adjunct therapy in patients with poor antibody-producing capabilities,
      prophylaxis against certain types of infections, and several autoimmune
      disorders, including idiopathic thrombocytopenic purpura and Kawasaki disease.
      Numerous mechanisms have been proposed to explain the beneficial effects of IGIV,
      including the interaction of infused IgG with fragment crystallizable (Fc)
      receptors and complement proteins, the modulation of synthesis and release of
      cytokines and cytokine antagonists, and neutralization of circulating
      autoantibodies.IGIV products differ significantly in methods of production, virus
      elimination, formulation, and composition. These differences can potentially have
      an impact on safety, tolerability, and efficacy. The major features affecting
      tolerability include volume load, sugar and salt content, and osmolality. Case
      studies highlight how these product characteristics could affect patient
      outcomes. CONCLUSION: While numerous mechanisms have been proposed to explain the
      beneficial effects of IGIV, the specific mechanisms remain elusive. Patient
      outcomes can be affected by IGIV product characteristics. The choice of an IGIV
      product should be matched to the patient's risk-factor profile.

PMID- 16100385
TI  - Practical considerations for the use of IGIV therapy: introduction.

PMID- 16100386
TI  - Pharmacy considerations for the use of IGIV therapy.
AB  - PURPOSE: A number of immunoglobulin intravenous (IGIV) products have been
      approved by the Food and Drug Administration (FDA) and are available
      commercially. Factors that need to be taken into consideration when selecting an
      appropriate IGIV product are discussed. SUMMARY: Pathogen safety is of particular
      concern in IGIV products. Manufacturers of IGIV products have introduced
      different steps to ensure pathogen inactivation and clearance. Physical viral
      inactivation methods include heat and pasteurization. Chemical viral inactivation
      methods include acidic treatment, solvent/detergent, and caprylate. Viral removal
      is accomplished via precipitation, chromatography, or nanofiltration. Pathogen
      inactivation processes may inadvertently affect IGIV product characteristics,
      including composition, concentration, purity, and yield, which may, in turn,
      affect tolerability, efficacy, and convenience of usage. Tolerability of IGIV
      products is dependent on factors such as volume load, osmolarity, IgA content,
      and stabilizing agent. For example, sucrose, used as a stabilizing agent in some
      IGIV products, has been associated with an increased risk of IGIV-induced acute
      renal failure. The qualities of IGIV products that contribute to convenience of
      usage for patients and healthcare professionals include liquid formulation,
      longer shelf life, multiple package sizes, and shorter infusion time. Cost
      effectiveness of therapy is another important consideration in IGIV product
      selection. Contributing factors to cost effectiveness include acquisition cost,
      reimbursement, product preparation, storage, shelf life, and adverse event
      management. CONCLUSION: The various IGIV products differ in terms of production
      process, tolerability, and convenience. Pharmacists should be cognizant of these
      differences when ordering IGIV therapy for their patients. Additionally, overall
      cost-effectiveness of therapy should be an important consideration.

PMID- 16100387
TI  - New signaling routes for an old drug: lipoxin A4 might mediate heme oxygenase-1
      induction by aspirin. Focus on "Novel lipid mediator aspirin-triggered lipoxin A4
      induces heme oxygenase-1 in endothelial cells".

PMID- 16100388
TI  - GIRK channels: hierarchy of control. Focus on "PKC-delta sensitizes Kir3.1/3.2
      channels to changes in membrane phospholipid levels after M3 receptor activation
      in HEK-293 cells".

PMID- 16100389
TI  - Pacemaker activity in urethral interstitial cells is not dependent on
      capacitative calcium entry.
AB  - The aim of the present study was to investigate the properties and role of
      capacitative Ca(2+) entry (CCE) in interstitial cells (IC) isolated from the
      rabbit urethra. Ca(2+) entry in IC was larger in cells with depleted
      intracellular Ca(2+) stores compared with controls, consistent with influx via a
      CCE pathway. The nonselective Ca(2+) entry blockers Gd(3+) (10 microM), La(3+)
      (10 microM), and Ni(2+) (100 microM) reduced CCE by 67% (n = 14), 65% (n = 11),
      and 55% (n = 9), respectively. These agents did not inhibit Ca(2+) entry when
      stores were not depleted. Conversely, CCE in IC was resistant to SKF-96365 (10
      microM), wortmannin (10 microM), and nifedipine (1 microM). Spontaneous transient
      inward currents were recorded from IC voltage-clamped at -60 mV. These events
      were not significantly affected by Gd(3+) (10 microM) or La(3+) (10 microM) and
      were only slightly decreased in amplitude by 100 microM Ni(2+). The results from
      this study demonstrate that freshly dispersed IC from the rabbit urethra possess
      a CCE pathway. However, influx via this pathway does not appear to contribute to
      spontaneous activity in these cells.

PMID- 16100390
TI  - Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated
      into denervated skeletal muscle in mice.
AB  - In this study, we examined pathophysiological roles of osteoactivin, a
      functionally unknown type I membrane glycoprotein, in mouse skeletal muscle
      atrophied by denervation (sciatic neurectomy). Denervation increased the amounts
      of osteoactivin, vimentin, matrix metalloproteinase-3 (MMP-3), and MMP-9 in mouse
      gastrocnemius muscle. Interestingly, immunohistochemical analysis revealed that
      vimentin, MMP-3, and MMP-9 were mainly present in fibroblast-like cells
      infiltrated into denervated mouse gastrocnemius muscle, whereas osteoactivin was
      expressed in the sarcolemma of myofibers adjacent to the fibroblast-like cells.
      On the basis of these findings, we reasoned that osteoactivin in myocytes was
      involved in activation of the infiltrated fibroblasts. To address this issue, we
      examined effects of osteoactivin on expression of MMPs in fibroblasts in vitro
      and in vivo. Overexpression of osteoactivin in NIH-3T3 fibroblasts induced
      expression of MMP-3, but not in mouse C(2)C(12) myoblasts, indicating that
      osteoactivin might functionally target fibroblasts. Treatment with recombinant
      mouse osteoactivin increased the amounts of collagen type I, MMP-3, and MMP-9 in
      mouse NIH-3T3 fibroblasts. The upregulated expression of these fibroblast marker
      proteins was significantly inhibited by heparin, but not by an integrin
      inhibitor, indicating that a heparin-binding motif in the extracellular domain
      might be an active site of osteoactivin. In osteoactivin-transgenic mice,
      denervation further enhanced expression of MMP-3 and MMP-9 in fibroblasts
      infiltrated into gastrocnemius muscle, compared with wild-type mice. Our present
      results suggest that osteoactivin might function as an activator for fibroblasts
      infiltrated into denervated skeletal muscles and play an important role in
      regulating degeneration/regeneration of extracellular matrix.

PMID- 16100391
TI  - High pressure enhances hexacoordination in neuroglobin and other globins.
AB  - The techniques of high applied pressure and flash photolysis have been combined
      to study ligand rebinding to neuroglobin (Ngb) and tomato Hb, globins that may
      display a His-Fe-His hexacoordination in the absence of external ligands. High
      pressure induces a moderate decrease in the His association rate and a large
      decrease in His dissociation rate, thus leading to an enhancement of the overall
      His affinity. The overall structural difference between penta- and
      hexacoordinated globins may be rather small and can be overcome by external
      modifications such as high pressure. Over the pressure range 0.1-700 MPa (7
      kbar), the globins may show a loss of over a factor of 100 in the amplitude of
      the bimolecular rebinding phase after photodissociation. The kinetic data show
      that pressure induces a moderate increase of the rate for ligand binding from the
      correlated pair state (just after photodissociation) and a large (factor of 1000)
      decrease in rate for migration through the protein. The effect on the ligand
      migration phase was similar for both the external ligands (such as oxygen) as for
      the internal (histidine) ligand, suggesting the dominant role of protein
      fluctuations, rather than specific chemical barriers. Thus high pressure
      efficiently closes the protein migration channels; however, contrary to the
      effect of high viscosity, high pressure induces a greater decrease in rate for
      ligand migration toward the exterior (heme to the solvent) versus inward
      migration, as if the presence of the ligand itself induces an additional steric
      constraint.

PMID- 16100392
TI  - Redox and spectroscopic properties of the Escherichia coli nitric oxide
      detoxifying system involving flavorubredoxin and its NADH-oxidizing redox
      partner.
AB  - Under anaerobic conditions, the flavodiiron NO-reductase from Escherichia coli
      (flavorubredoxin, FlRd) constitutes one of the major protective enzymes against
      nitric oxide. The redox and spectroscopic properties of the rubredoxin (Rd), non
      heme diiron, and FMN sites of flavorubredoxin were determined, which was
      complemented by the study of truncated versions of FlRd: one consisting only of
      its rubredoxin module, and another consisting of its flavodiiron structural core
      (lacking the Rd domain). The studies here reported were performed by a
      combination of potentiometry with visible and EPR spectroscopies. Moreover, we
      present the first direct EPR evidence for the presence of the non-heme diiron
      site in the flavodiiron proteins family. Also, the redox properties of the FlRd
      physiological partner, the NADH:flavorubredoxin oxidoreductase (FlRd-Red), were
      determined. It is further shown that the redox properties of this complex
      electron transfer system are fine-tuned upon interaction of the two enzymes.

PMID- 16100393
TI  - Apoptosis-associated tyrosine kinase (AATYK) has differential Ca2+-dependent
      phosphorylation states in response to survival and apoptotic conditions in
      cerebellar granule cells.
AB  - In dissociated cultures of cerebellar granule cells, extracellular high potassium
      (HK) and low potassium (LK) concentrations control cell survival and apoptosis,
      respectively. Apoptosis-associated tyrosine kinase (AATYK) is up-regulated during
      the LK-induced apoptosis. Overexpression of wild-type AATYK, but not its kinase
      deficient mutant, stimulates apoptosis in LK. In this study, we analyzed the
      relationship between the phosphorylation states of AATYK and the survival of
      granule cells. AATYK was hypophosphorylated in HK, whereas it was
      hyperphosphorylated in apoptotic LK. HK-dependent hypophosphorylation of AATYK
      was controlled by L-type voltage-dependent calcium channel-mediated Ca2+ influx
      followed by Ca2+-dependent protein phosphatase activity. However, LK-induced
      hyperphosphorylation of AATYK at multiple sites was blocked by kainate, lithium,
      and protein kinase C-delta inhibitor. AATYK phosphorylation was concurrent with c
      Jun phosphorylation. In addition, mutations of AATYK on either the kinase domain
      or Ser-480, Ser-558, and Ser-566 residues suppressed the LK-induced
      hyperphosphorylation and apoptosis, suggesting the involvement of self-kinase
      activity and these Ser residues in this process. Our data therefore indicate that
      the phosphorylation states of AATYK are closely related to the HK-induced
      survival and LK-induced apoptosis of cerebellar granule cells.

PMID- 16100394
TI  - Plant villin, lily P-135-ABP, possesses G-actin binding activity and accelerates
      the polymerization and depolymerization of actin in a Ca2+-sensitive manner.
AB  - From germinating pollen of lily, two types of villins, P-115-ABP and P-135-ABP,
      have been identified biochemically. Ca(2+)-CaM-dependent actin-filament binding
      and bundling activities have been demonstrated for both villins previously. Here,
      we examined the effects of lily villins on the polymerization and
      depolymerization of actin. P-115-ABP and P-135-ABP present in a crude protein
      extract prepared from germinating pollen bound to a DNase I affinity column in a
      Ca(2+)-dependent manner. Purified P-135-ABP reduced the lag period that precedes
      actin filament polymerization from monomers in the presence of either Ca(2+) or
      Ca(2+)-CaM. These results indicated that P-135-ABP can form a complex with G
      actin in the presence of Ca(2+) and this complex acts as a nucleus for
      polymerization of actin filaments. However, the nucleation activity of P-135-ABP
      is probably not relevant in vivo because the assembly of G-actin saturated with
      profilin, a situation that mimics conditions found in pollen, was not accelerated
      in the presence of P-135-ABP. P-135-ABP also enhanced the depolymerization of
      actin filaments during dilution-mediated disassembly. Growth from filament barbed
      ends in the presence of Ca(2+)-CaM was also prevented, consistent with filament
      capping activity. These results suggested that lily villin is involved not only
      in the arrangement of actin filaments into bundles in the basal and shank region
      of the pollen tube, but also in regulating and modulating actin dynamics through
      its capping and depolymerization (or fragmentation) activities in the apical
      region of the pollen tube, where there is a relatively high concentration of
      Ca(2+).

PMID- 16100395
TI  - Pharmacogenomics: historical perspective and current status.
AB  - Pharmacogenomics is an extension of pharmacogenetics, a science described here in
      terms of five stages of development: 1) some clinical observations predicted
      genetic alterations of drug response; 2) additional case discoveries led to the
      term "pharmacogenetics," a concept broadened by 3) many systemic case studies,
      and the realization of its wide applicability; 4) came the recognition of
      systematic pharmacogenetic differences between human populations. Then it became
      clear that 5) most human drug-response differences were multifactorial, caused by
      many genetic alterations plus environmental factors. The recognition of these
      complexities, and the advance of genetics into genomics led to the broader
      science of pharmacogenomics. This led to plans to create "personalized medicine,"
      that is, making drug use more effective and safer by giving drugs that fit a
      person's genes. Much of the science of genetics, dealing with gene structure, was
      changed by the realization that gene expression and thereby gene function was
      variable; this leads to systematic studies of drug action on genes, reversing the
      traditional studies of genes affecting drug action. Finally, the realization that
      gene-protein variations contribute to most common diseases leads to efforts of
      creating new drugs that act on these variants.

PMID- 16100396
TI  - Transfection assays with allele-specific constructs: functional analysis of UDP
      glucuronosyltransferase variants.
AB  - Adverse drug reactions (ADRs) are a major clinical problem. A rapidly growing
      body of evidence suggests that genetic factors, at least in part, determine
      individual susceptibility to ADRs. A large number of pharmacogenetic studies have
      identified a number of polymorphisms as predictors of drug efficacy and/or
      adverse events. These candidate markers should be investigated further to
      ascertain the underlying mechanism of action, for example, changes in the kinetic
      parameters of an enzyme, or transcriptional activity of a promoter region. In
      this chapter, we describe a transient transfection assay for the functional
      characterization of naturally occurring variants of UDP-glucuronosyltransferase
      (UGT) 1A1. This phase II drug metabolizing enzyme is involved in the
      glucuronidation of SN-38, an active metabolite of the anti-cancer drug
      irinotecan. Single-nucleotide polymorphisms of the UGT1A1 gene have been
      correlated to irinotecan-induced ADRs. Variant UGT1A1s are heterologously
      expressed in COS-1 cells and characterized in terms of the level of protein
      expression and enzyme kinetics.

PMID- 16100397
TI  - Snapshot of the allele-specific variation in human gene expression.
AB  - The analysis of gene differential expression is complicated by the potentially
      subtle differences associated with alterations in a single allele as well as by
      variations between individuals that arise from environmental or physiological
      factors. To circumvent these analytic problems, a method, named allele-specific
      differential expression analysis, was developed to compare the relative
      expression levels of two alleles of the same gene within the same cellular
      sample. The studies of allele-specific expression revealed that differential
      expression is relatively common in the human population.

PMID- 16100398
TI  - Genome-wide analysis of allele-specific gene expression using oligo microarrays.
AB  - Human variation is largely caused by deoxyribonucleic acid polymorphism and
      difference in gene expression. Common disease/common variant hypotheses suggest
      that quantitative differences among different alleles may be the basis for
      complex diseases. Quantitative difference in gene expression between alleles may
      affect most complex diseases. We have developed a gene chip-based method to
      quantitatively examine allele-specific gene expression of 1063 transcribed single
      nucleotide polymorphisms using Affymetrix HuSNP oligo arrays. Among the 602 genes
      that were heterozygous and expressed in kidney or liver tissues from seven
      individuals, 326 (54%) showed preferential expression of one allele in at least
      one individual. The genes that showed allele-specific expression are distributed
      throughout the genome. We showed that variation of gene expression between
      alleles is common and that this variation may contribute to human variation. Our
      studies demonstrate the feasibility to perform genome-wide analysis of allele
      specific gene expression.

PMID- 16100399
TI  - HaploChIP: an in vivo assay.
AB  - The characterization of protein-deoxyribonucleic acid (DNA) interactions
      occurring at an allele-specific level is important to resolving the functional
      consequences of genetic variation in non-coding DNA for gene expression and
      regulation. The approach of haplotype-specific chromatin immunoprecipitation
      (i.e., haploChIP) resolves in living cells relative protein-DNA binding to a
      particular allele through immunoprecipitation of proteins crosslinked to DNA.
      Single-nucleotide polymorphisms present in a heterozygous form are used as
      markers to differentiate allelic origin. This in turn allows resolution of
      specific haplotypes showing differences in relative protein occupancy. The
      haploChIP approach allows testing of in vitro hypotheses that a transcription
      factor protein shows haplotype specific occupancy. In addition, the haploChIP
      approach allows screening of haplotypes for differences in relative gene
      expression by immunoprecipitation using antibodies to phosphorylated Pol II.

PMID- 16100400
TI  - Aspects influencing genotyping method selection.
AB  - The variety of genotyping methods currently available and the evolution of their
      capabilities have facilitated an expansion of the field of pharmacogenomics.
      Traditionally, limited genotyping capabilities have restricted the generation and
      application of genotyping data for pharmacogenomic studies. With the variety of
      platforms and chemistries available for flexible, high-throughput genotyping, it
      is important to keep in mind the limitations imposed by both the polymorphisms
      that are to be interrogated and the type of pharmacogenomics study for which the
      data are being generated. This chapter is an overview of the constraints these
      factors impose on different genotyping methods and describes aspects important to
      the integration of genotyping into a pharmacogenomics study.

PMID- 16100401
TI  - Denaturing high-performance liquid chromatography for mutation detection and
      genotyping.
AB  - Denaturing high-performance liquid chromatography (DHPLC) is an accurate and
      efficient screening technique used for detecting deoxyribonucleic acid sequence
      changes by heteroduplex analysis. It can also be used for genotyping of single
      nucleotide polymorphisms. The high-sensitivity of DHPLC has made this technique
      one of the most reliable approaches to mutation analysis and is used in various
      areas of genetics, both in the research and clinical arena. This chapter
      describes the methods used for mutation detection analysis and the genotyping of
      single-nucleotide polymorphisms by DHPLC on the WAVETM system from Transgenomic
      Inc.

PMID- 16100402
TI  - Pyrosequencing of clinically relevant polymorphisms.
AB  - The data generated from the Human Genome Project has led to an explosion of
      technology for low-, medium-, and high-throughput genotyping methods.
      Pyrosequencing is a genotyping assay based on sequencing by synthesis. Short runs
      of sequence around each polymorphism are generated, allowing for internal
      controls for each sample. Pyrosequencing can also be used to identify tri
      allelic, indel, and short-repeat polymorphisms, as well as determining allele
      percentages for methylation or pooled sample assessment. Assays details for
      Pyrosequencing of clinically relevant polymorphisms are described in this
      chapter.

PMID- 16100403
TI  - Kinetic fluorescence-quenching detection assay for allele frequency estimation.
AB  - The analysis of human genetic variations, such as single-nucleotide polymorphisms
      (SNPs), has great applications in genome-wide association studies of complex
      genetic traits. We have developed an SNP genotyping method based on the primer
      extension assay with fluorescence quenching detection. The template-directed dye
      terminator incorporation with fluorescence quenching detection (FQ-TDI) assay is
      based on the observation that the intensity of fluorescent dye R110- and R6G
      labeled acycloterminators is universally quenched once they are incorporated onto
      a deoxyribonucleic acid (DNA) oligonucleotide primer. By comparing the rate of
      fluorescence quenching of the two allelic dyes in real time, we have extended
      this method for allele frequency estimation of SNPs in pooled DNA samples. The
      kinetic FQ-TDI assay is highly accurate and reproducible both in genotyping and
      in allele frequency estimation. Allele frequencies estimated by the kinetic FQ
      TDI assay correlated well with known allele frequencies, with an r2 value of
      0.993. Applying this strategy to large-scale studies will greatly reduce the time
      and cost for genotyping hundreds and thousands of SNP markers between affected
      and control populations.

PMID- 16100404
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Major strengths of mass spectrometry analysis include the accuracy of the
      detection principle and the automatic data storage, making it a premier choice
      for high-throughput single-nucleotide polymorphism genotyping. We explain the
      assay principle in detail and give step-by-step laboratory instructions. Finally,
      references point toward further use of mass spectrometry analysis for molecular
      haplotyping, pooled DNA analysis, re-sequencing, and gene expression studies.

PMID- 16100405
TI  - Fluorescence-based fragment size analysis.
AB  - The successful application of capillary electrophoresis technology to the
      genotyping of various types of polymorphisms has been well documented. The
      flexibility and automation of the Applied Biosystems 3100 Genetic Analyzer make
      it an excellent capillary electrophoresis platform for the generation of high
      quality genotype data. These data are readily applied to pharmacogenomic
      investigations of various types. Included in this chapter is a protocol for the
      generation of genotype data using minimal template deoxyribonucleic acid and
      maximizing the automation of both data analysis and genotype assignment through
      the use of the Applied Biosystems GeneMapper 3.0 software package.

PMID- 16100406
TI  - Single-nucleotide polymorphism genotyping in DNA pools.
AB  - To undertake partial, or complete, genome screens by association-based
      methodology for quantitative trait loci, multiple individuals have to be screened
      for large numbers of genetic markers. Consequently, much recent interest has
      focused on methods enabling accurate allele quantification in pooled
      deoxyribonucleic acid (DNA) samples. Microsatellites were the favored markers in
      initial studies, but the extraordinary wealth of data concerning single
      nucleotide polymorphisms (SNPs) has turned attention to the quantification of SNP
      alleles in pools. All such approaches require accurate estimation of DNA
      concentrations, followed by the preparation of replicate pools, their validation,
      and application of procedures for determining allele frequencies. This chapter
      describes the important steps in preparing pools and surveys a variety of
      techniques that have been proposed for SNP detection. Finally, we describe the
      application of a generic approach using pooled DNA for detection of allele
      frequency differences between case and control populations based on primer
      extension protocols and outline a strategy for estimating SNP allele frequencies
      employing microarrays.

PMID- 16100407
TI  - TaqMan genotyping of insertion/deletion polymorphisms.
AB  - The 5' fluorogenic (TaqMan) assay has been successfully used in screening for
      single-nucleotide polymorphisms; the very few steps required and the ability to
      automate each step allow for high-throughput screening. Insertion/deletion
      polymorphisms are an important class of markers that can be studied for different
      applications, such as diagnostics, genome variation, and species identification.
      Polymerase chain reaction (PCR) and post-PCR analysis are required to score the
      insertion or the deletion allele. In this chapter, we describe an expansion of
      the TaqMan technology for a rapid, high-throughput, screening for
      insertion/deletion polymorphisms in which the exact endpoints are known. The
      method requires minimal post-PCR analysis and can be applied to polymorphisms of
      any size.

PMID- 16100408
TI  - PharmGKB: the pharmacogenetics and pharmacogenomics knowledge base.
AB  - The Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB) is an
      interactive tool for researchers investigating how genetic variation effects drug
      response. The PharmGKB web site, www.pharmgkb.org, displays genotype, molecular,
      and clinical primary data integrated with literature, pathway representations,
      protocol information, and links to additional external resources. Users can
      search and browse the knowledge base by genes, drugs, diseases, and pathways.
      Registration is free to the entire research community but subject to an agreement
      to respect the rights and privacy of the individuals whose information is
      contained within the database. Registered users can access and download primary
      data to aid in the design of future pharmacogenetics and pharmacogenomics
      studies.

PMID- 16100409
TI  - Systems for the management of pharmacogenomic information.
AB  - Recent breakthroughs in biological research have been made possible by remarkable
      advances in high-performance computing and the establishment of a highly
      sophisticated information technology infrastructure. This chapter gives an
      overview of the main and most important technologies needed for the management of
      pharmacogenomic information, namely database management systems and software and
      hardware architectures. Because pharmacogenomics deals with a great many of
      public and/or proprietary data, the most prominent ways for easy storage,
      retrieval, analysis, and exchange are presented. Processing these data requires
      the use of sophisticated software architectures. Several most recent practices
      useful for a pharmacogenomic environment are explained. Multitiered application
      design and web services are discussed and described independent of the major
      enterprise development platforms. Because life sciences are becoming increasingly
      quantitative and because state-of-the-art software architectures use many system
      resources, this chapter presents the most recent and powerful systems for
      parallel data processing and data storage. Finally, shared and distributed memory
      systems and combinations of them as well as different storage architectures such
      as directly attached storage, network-attached storage, and storage-area network
      are explained in detail.

PMID- 16100411
TI  - Handling characteristics of precoated and operator-coated brackets.

PMID- 16100412
TI  - Time is of the essence.

PMID- 16100413
TI  - Six keys to nonextraction treatment.

PMID- 16100414
TI  - One pathway to successful orthodontic practice.

PMID- 16100415
TI  - Three-dimensional radiographic analysis in orthodontics.

PMID- 16100416
TI  - A simplified appliance for forced eruption.

PMID- 16100417
TI  - Orthodontic treatment of a patient with Type 1 diabetes mellitus.

PMID- 16100418
TI  - Bacteriophage-based tests for tuberculosis.

PMID- 16100419
TI  - Alternatives to the tuberculin skin test: interferon-gamma assays in the
      diagnosis of mycobacterium tuberculosis infection.
AB  - For nearly a century, there were no alternatives to the tuberculin skin test
      (TST) for diagnosing latent tuberculosis infection. Because of advances in
      immunology and genomics, for the first time, an alternative has emerged in the
      form of T cell based interferon-g (IFN-gamma) assays, a new generation of in
      vitro tests of cellular immunity. These assays measure cell mediated immune
      response by quantifying IFN-gamma released by T cells in response to stimulation
      by Mycobacterium tuberculosis antigens. Although early versions of IFN-gamma
      assays used purified protein derivative (PPD) as the stimulating antigen, newer
      versions use antigens that are significantly more specific to M. tuberculosis.
      These specific antigens include ESAT-6 and CFP-10. These proteins, encoded by
      genes located within the region of difference 1 (RD1) segment of the M.
      tuberculosis genome, are more specific to M. tuberculosis than PPD because they
      are not shared with any BCG substrains or several nontuberculous mycobacterial
      species. A review of current evidence on the performance of IFN-gamma assays and
      TST suggests that both the TST and IFN-gamma assays have advantages and
      limitations, and both tests appear to be useful at this time. The emergence of
      IFN-gamma assays is a much anticipated, welcome development that has, for the
      first time, increased the choice of tests available for diagnosing latent
      tuberculosis infection. Because both tests have their strengths and limitations,
      the decision to select one over the other will depend on the population, the goal
      of testing, and the resources available. To fully evaluate the utility of IFN
      gamma assays in high burden countries such as India, long-term cohort studies are
      needed to determine the association between positive IFN-gamma results and the
      subsequent risk of active disease.

PMID- 16100420
TI  - Quality control of culture media in a microbiology laboratory.
AB  - The nature of reporting of a microbiology laboratory depends upon the quality of
      the culture media used. Quality of media directly affects the observations and
      inferences drawn from the cultural characteristics of microorganisms. Checking of
      different parameters of media such as growth supporting characteristics, physical
      characteristics, gel strength and batch contamination can help to assess their
      quality. There are different methods to check all these parameters
      systematically. The meticulous performance of quality control of culture media
      can assure precision in reporting.

PMID- 16100421
TI  - Seroprevalence and incidence of rubella in and around Delhi (1988-2002).
AB  - National Institute of Communicable Diseases (NICD) has been engaged in rubella
      testing for serodiagnosis of the infection and screening for immunity status. The
      compiled and evaluated data of the work done on rubella testing for the past
      fifteen years has been presented here to show the trend and changing scenario of
      the disease in Delhi. Blood samples were from 7424 patients referred to NICD,
      Delhi for serodiagnosis of congenital Rubella syndrome (CRS) in malformed babies,
      in utero rubella infection in women and immunity status of pregnant women and
      women with bad obstetric history. They were tested for rubella IgG and/or rubella
      IgM antibodies using commercially available reagents and kits. The data from the
      15 years of testing was then compiled and evaluated. From the available data it
      was seen that immunity status against rubella in childbearing age group of women
      increased steadily from 49% in 1988 to 87% in 2002. Reported cases of CRS at NICD
      are also on the decline over the time period. There is periodic indication of
      high incidence of rubella in the year 1988; 1991 and 1998 as the reported cases
      of acute rubella infection in childbearing age group is high during these years.

PMID- 16100422
TI  - Susceptibility trends of pseudomonas species from corneal ulcers.
AB  - PURPOSE: To assess the changing trends in the antibiotic susceptibility of
      Pseudomonas spp . isolated from bacterial keratitis over a nine year period with
      special emphasis on fluoroquinolone susceptibilities. METHODS: All corneal
      scraping cultures positive for Pseudomonas spp. (n=585) isolated from patients
      with bacterial keratitis at the Aravind Eye Hospital, Madurai from 1995-2003 were
      evaluated. Cultures were performed in liquid and solid media and susceptibility
      testing was done against amikacin, gentamicin, tobramycin, ciprofloxacin and
      ofloxacin by Kirby-Bauer disc diffusion method. RESULTS: The susceptibility of
      Pseudomonas spp. was over 90% from 1995-1998 to ciprofloxacin which decreased to
      83% from 1999-2003. The total number of isolates resistant to ciprofloxacin was
      51 (9.4%). No statistically significant increase in the number of isolates
      resistant to ciprofloxacin was noted. Ofloxacin showed 54% susceptibility from
      1995-1998 but increased to 64% from 1999-2003. Analysis of in vitro activity of
      amikacin reveals that there was 43% sensitivity from 1995-1998 but later it
      increased to 76% from 1999-2003. In case of gentamicin, the sensitivity decreased
      marginally from 80% to 70% through the years. Tobramycin showed 45% sensitivity
      from 1995-1998 but increased to 75% from 1999-2003. CONCLUSIONS: The
      fluoroquinolones remain a good choice in the treatment of ocular infections, with
      high susceptibility of Pseudomonas spp. Among the aminoglycosides, gentamicin was
      found to be highly effective against Pseudomonas corneal ulcers when compared to
      amikacin and tobramycin. The results show a need for continuous monitoring of
      bacterial resistance trends.

PMID- 16100423
TI  - Non tuberculous mycobacteria isolated from clinical specimens at a tertiary care
      hospital in South India.
AB  - PURPOSE: This is a retrospective analysis of the isolation rates of
      nontuberculous mycobacteria (NTM) from various clinical specimens and their
      antimicrobial susceptibility patterns. METHODS: All NTM isolated between 1999 and
      2004 at Christian Medical College, Vellore, South India, were identified with
      various biochemical tests. Antimicrobial susceptibility test for all NTM was
      performed by standard methods. RESULTS: A total of 32,084 specimens were received
      for culture, of which 4473 (13.9%) grew acid fast bacilli (AFB). Four thousand
      three hundred (96.1%) of the AFB were M. tuberculosis while 173 (3.9%) were NTM.
      Of the 173 NTM, 115 (66.5%) were identified to the species level. Pus, biopsy
      specimens and sputum specimens yielded most of the NTM of which M. chelonae (46%)
      and M. fortuitum (41%) accounted for majority of them. M. chelonae and M.
      fortuitum, showed highest susceptibility to amikacin (99.2%). NTM were repeatedly
      isolated from seven sputum specimens, 15 biopsy and pus specimens, two CSF and
      two blood cultures. Six were isolated from patients with AIDS and five from post
      transplant patients. CONCLUSIONS: The isolation of NTM from various clinical
      specimens is reported in this study to highlight the associated diseases and
      therapeutic options in these infections.

PMID- 16100424
TI  - Evaluation of the polymerase chain reaction analysis for diagnosis of falciparum
      malaria in Delhi, India.
AB  - Plasmodium falciparum infections are frequently fatal if untreated and hence need
      to be diagnosed and treated early. Malaria diagnosis, with conventional Giemsa
      staining as a gold standard, has had several limitations. New rapid and accurate
      methods are needed for diagnosis. In this study, polymerase chain reaction (PCR)
      analysis specific for diagnosis of P. falciparum was evaluated. For the study,
      blood samples were collected from 310 patients suspected of having malaria. PCR
      analysis for P. falciparum from venous blood and at the same time Giemsa staining
      of thick and thin blood smears was done. A total of 160 (51.6 %) samples were
      positive for malarial parasite of which 63 (39.4 %) were positive for P.
      falciparum by Giemsa staining while 61 (38.1 %) were positive for P. falciparum
      by PCR analysis. Giemsa staining was time consuming, laborious and may give poor
      results in cases with low parasitaemia. The PCR analysis for P. falciparum was
      able to detect 3 cases of low parasitaemia missed initially on Giemsa staining,
      was 96.8 % sensitive, 100% specific but was very costly, needed a lot of practice
      and standardization and was time consuming. PCR analysis can be used to
      supplement the conventional Giemsa staining for reliable diagnosis of falciparum
      malaria especially in cases with low parasitaemia.

PMID- 16100425
TI  - Efficacy of fluorochrome stain in the diagnosis of pulmonary tuberculosis co
      infected with HIV.
AB  - The resurgence of Mycobacterium tuberculosis in association with HIV infection
      has focussed much attention in the rapid diagnosis of high risk cases. Infection
      with HIV is known to alter the presentation of pulmonary tuberculosis. The
      present study was under taken to compare the efficacy of fluorochrome stain (Fl)
      with conventional Ziehl Neelsen (ZN) stain in the diagnosis of pulmonary
      tuberculosis. Two hundred cases of pulmonary tuberculosis were included in the
      study. Sputum smears were screened for acid fast bacilli (AFB) by ZN and Fl
      methods and blood samples were screened for HIV. Sputum positive cases detected
      by Fl stain were higher in number (69%) when compared to ZN stain (50%). Of the
      total cases studied 15.5% were HIV seropositive. CONCLUSIONS: Fluorochrome
      staining was found to be more efficient (45%) when compared to ZN staining (29%)
      in detecting cases associated with HIV seropositivity, especially paucibacillary
      cases.

PMID- 16100426
TI  - Sunflower seed husk agar: a new medium for the differentiation of Candida
      dubliniensis from Candida albicans.
AB  - A sunflower (Helianthus annuus) seed husk agar medium has been developed and
      evaluated for differentiation of Candida dubliniensis from Candida albicans on
      the basis of colony morphology and chlamydospore production. All C. dubliniensis
      isolates (n=40) produced rough colonies with hyphal fringes and abundant
      chlamydospores whereas 101 of 105 (96.2%) C. albicans isolates produced smooth
      colonies with no evidence of chlamydospore production. Since this medium is free
      from oil droplets, chlamydospores can be examined with greater clarity by Dalmau
      plate technique. This medium provides a simple and cost-effective tool for the
      presumptive differentiation of C. dubliniensis from C. albicans and is
      particularly suited for clinical microbiology laboratories where biochemical or
      molecular methods for the differentiation of these two species are not available.

PMID- 16100427
TI  - Survey of Staphylococcus isolates among hospital personnel, environment and their
      antibiogram with special emphasis on methicillin resistance.
AB  - The objective of this study was to find the prevalence of Staphylococcus spp.
      carriage among hospital personnel and hospital environment and their antibiogram
      with special emphasis on methicillin resistance. A total of 205 samples from
      hospital personnel and environment were collected from casualty, oncology and
      multidisciplinary cardiac unit ward of Kasturba Medical College Hospital,
      Manipal. Samples were collected using sterile cotton wool swabs and inoculated
      into brain heart infusion broth. Subcultures were done onto blood agar and
      MacConkey's agar. Isolates were identified by standard methods up to species
      level. Antimicrobial susceptibility test was performed according to standardized
      disc diffusion Kirby-Bauer method. Each of the isolates was screened for
      methicillin resistance using oxacillin disc on Mueller Hinton agar plate followed
      by MIC for methicillin and cefoxitin susceptibility test by disc diffusion
      method. Sixty five out of 205 strains (31.7%) were Staphylococcus spp. and all of
      them were coagulase negative. Most of the strains belonged to S.epidermidis
      49.23% (32/65) followed by S. saprophyticus 26.15% (17/65). Maximum isolates of
      S.epidermidis were from anterior nares 28.12% (9/32 strains of S.epidermidis).
      Highest number of methicillin resistant coagulase negative strains (3/9, 33.33%)
      were isolated from stethoscope of multidisciplinary cardiac unit ward followed by
      carriers in the anterior nares (2/9, 22.22%). Methicillin resistant coagulase
      negative staphylococci are prevalent in anterior nares of hospital personnel and
      in the hospital environment thereby providing a definite source for hospital
      acquired infection. All isolates were sensitive to vancomycin, ciprofloxacin and
      amikacin.

PMID- 16100428
TI  - Incidence of carbapenem resistant nonfermenting gram negative bacilli from
      patients with respiratory infections in the intensive care units.
AB  - Resistance to carbapenems is commonly seen in nonfermenting gram negative bacilli
      (NFGNB). We document herein the prevalence of carbapenem resistance in NFGNB
      isolated from patients with respiratory tract infections in the intensive care
      units (ICUs). A total of 460 NFGNB were isolated from 606 endotracheal aspirate
      specimens during January through December 2003, of which 56 (12.2%) were found to
      be resistant to imipenem and meropenem. Of these, 24 (42.8%) were Pseudomonas
      aeruginosa , 8 (14.2%) were Acinetobacter spp. and 24 (42.8%) were other NFGNB.
      Stringent protocols such as antibiotic policies and resistance surveillance
      programs are mandatory to curb these bacteria in ICU settings

PMID- 16100429
TI  - Mycobacterium avium intracellularae complex associated extrapulmonary axillary
      lymphadenitis in a HIV-seropositive infant--a rare case report.
AB  - Opportunistic infections by Mycobacterium avium intracellulare complex in HIV
      infected patients, though common in adults, are rarely seen in infants. We
      herewith report an interesting case of an eight month old infant presenting with
      isolated axillary lymphadenitis, later on diagnosed to be tubercular
      lymphadenitis by Mycobacterium avium intracellulare and finally proved to be
      seropositive for HIV infection born to previously undetected HIV seropositive
      parents.

PMID- 16100430
TI  - Invasive aspergillosis involving multiple paranasal sinuses--a case report.
AB  - A case of invasive multiple paranasal sinus aspergillosis with bony involvement
      is reported. A young immunocompetent lady presented with bilateral nasal
      obstruction due to polyps. Radiologically and histopathologically a fungal cause
      was kept a possibility, and the diagnosis of Aspegillus fumigatus was established
      by demonstration of acute angle branching septate hyphae on direct wet mount and
      repeated isolation in culture. Patient responded favourably to surgical excision
      of polyps and oral itraconazole post operatively.

PMID- 16100431
TI  - Fusarium solani breast abscess.
AB  - An unusual manifestation of breast fusariosis was encountered in a 55-year-old
      female diabetic patient. Two fine needle aspirates (FNA) from the abscess were
      done at three days interval and they showed hyaline, septate, branched, fungal
      hyphae in 10% potassium hydroxide mount. Fungal infection was confirmed by
      demonstrating the fungal hyphae in the midst of lymphocytes, macrophages and
      neutrophils in Leishman stained smears. Culture of both FNAs yielded a heavy and
      pure growth of Fusarium solani. The patient responded to oral ketoconazole 200 mg
      once daily for 3 weeks. The breast fusariosis reported here is presumably the
      first case in India.

PMID- 16100432
TI  - Epidural mass due to aspergillus flavus causing spinal cord compression--a case
      report and brief update.
AB  - Aspergillus infection of the central nervous system (CNS) is an uncommon disease.
      Most of the reported cases are of sinocranial spread and cases with contiguous
      spread to spinal cord from lung and other organs are uncommon. A case of
      pulmonary aspergillosis with extension to thoracic vertebrae forming a paraspinal
      mass resulting in neurological deficit due to Aspergillus flavus, is reported.
      The 43 year old patient did not have any obvious predisposing condition. He
      presented with loss of motor function and succumbed to the infection despite
      operative intervention and antifungal therapy. A brief update on CNS
      aspergillosis is presented along with detailed clinical, radiological and
      laboratory work up of the patient.

PMID- 16100433
TI  - Salmonella nomenclature seen in the literature.

PMID- 16100434
TI  - Escherichia fergusonii: an emerging pathogen in South Orissa.

PMID- 16100435
TI  - Keratitis due to Colletotrichum dematium.

PMID- 16100437
TI  - Corticosteroid induced Cryptococcus meningitis.

PMID- 16100438
TI  - Antibiotic susceptibility pattern and plasmid profile of multidrug resistant
      Salmonella typhi.

PMID- 16100439
TI  - Prevalence of chronic fatigue and chronic fatigue syndrome in Korea: community
      based primary care study.
AB  - There have been many epidemiological and clinical researches on chronic fatigue
      (CF) and chronic fatigue syndrome (CFS) since the 1990s, but such studies have
      been quite limited in Korea. The aim of this study was to investigate the point
      prevalence of CF and CFS in patients who visited community-based eight primary
      care clinics in Korea. The study subjects were 1,648 patients aged 18 yr and over
      who visited one of eight primary care clinics in Korea between the 7th and 17th
      of May 2001. The physicians determined the status of the subjects through fatigue
      related questionnaires, medical history, physical examination, and laboratory
      tests. The subjects were categorized into no fatigue, prolonged fatigue, CF and
      then CF were further classified to medically explained CF (Physical CF and
      Psychological CF) and medically unexplained CF (CFS and idiopathic chronic
      fatigue). The point prevalence of CF and CFS were 8.4% (95% CI 7.1-9.7%) and 0.6%
      (95% CI 0.2-1.0%). Medically explained CF was 80.5% of CF, of which 57.1% had
      psychological causes. The clinical characteristics of CFS were distinguished from
      explained CF. CF was common but CFS was rare in community-based primary care
      settings in Korea.

PMID- 16100440
TI  - Differential effect of gamma-radiation-induced heme oxygenase-1 activity in
      female and male C57BL/6 mice.
AB  - Ionizing radiation produces reactive oxygen species, which exert diverse
      biological effects on cells and animals. We investigated alterations of heme
      oxygenase (HO) and non-protein thiols (NPSH), which are known as two major anti
      oxidant enzymes, in female and male C57BL/6 mice in the lung, liver, and brain
      after whole-body gamma-irradiation with 10 Gy (1-7 days) as well as in the lung
      after whole-thorax gamma-irradiation (WTI) with 12.5 Gy (1-26 weeks). Most
      significant alteration of HO activity was observed in the liver, which elevated
      250% in males. NPSH level in female liver was increased on the 5th-7th days but
      decreased in males on the 3rd day. In the lung, the elevation of HO activity in
      both sexes and the pattern of NPSH change were similar to that of the liver. On
      the other hand, the increase of HO activity on the 16th week and the decrease of
      NPSH level on the 2nd week were observed only in male lung after WTI. This study
      shows that the liver is the most sensitive tissue to gamma-irradiation-induced
      alterations of HO activity in both female and male mice. In addition, there
      exists significant differential effect of gamma-irradiation on anti-oxidant
      system in female and male mice.

PMID- 16100441
TI  - Distributions of antibody titers to Mycoplasma pneumoniae in Korean children in
      2000-2003.
AB  - The aim of study was to describe Mycoplasma pneumoniae epidemics in a hospital
      based population. Special attention was paid to the relationship between antibody
      titer to M. pneumoniae and sex, age, and atopy. During the eight 6-month periods
      between January 2000 and December 2003, serum samples were obtained from 1,319
      Korean children who presented with respiratory symptoms, and were examined for
      antibodies to M. pneumoniae using the indirect particle agglutination test.
      Geometric mean antibody titers peaked in the second half of 2000 and then
      decreased gradually, a second peak occurred in the second half of 2003. Likewise,
      the frequency of high antibody titers (> or =1:640) also peaked during these two
      periods. Antibody titers in children aged 0-3 yr were lower than in older
      children during both peak periods and for 2 yr after the first peak. Sex and
      atopy had no effect on antibody titers. During the years 2000-2003, geometric
      mean antibody titers and the frequencies of high antibody titers varied with
      time. These changes suggest a cyclic pattern of M. pneumoniae infection, with two
      epidemic peaks separated by 3 yr.

PMID- 16100443
TI  - IL-1beta acts in synergy with endogenous IL-1beta in A375-S2 human melanoma cell
      apoptosis through mitochondrial pathway.
AB  - Interleukin-1beta (IL-1beta) is a pivotal proinflammatory cytokine. To
      investigate the mechanism of IL-1beta-induced cell death in human malignant
      melanoma A375-S2 cells, MTT assay, photomicroscopical observation, DNA agarose
      gel electrophoresis, radioimmunoassay and Western blot analysis were carried out.
      IL-1beta did not only induce nuclear condensation and DNA fragmentation, but also
      increased degradation of two substrates of caspase-3, poly ADP-ribose polymerase
      (PARP) and inhibitor of caspase-activated DNase (ICAD). Simultaneously, release
      of precursor of IL-1beta (pro-IL-1beta) and endogenous IL-1beta production were
      involved in the apoptotic process. IL-1beta enhanced the ratio of Bax/Bcl-2 and
      Bax/Bcl-xL expression and up-regulated apoptosis inducing factor (AIF)
      expression, which required the activation of downstream caspases. These results
      suggest that IL-1beta induces endogenous IL-1beta production, enhances cleavage
      of caspase downstream substrates and promotes mitochondria mediated apoptosis in
      A375-S2 cells.

PMID- 16100442
TI  - Epigallocatechin-3-gallate suppresses galactose-alpha1,4-galactose-1beta,4
      glucose ceramide expression in TNF-alpha stimulated human intestinal epithelial
      cells through inhibition of MAPKs and NF-kappaB.
AB  - Intestinal epithelial cells (IECs) have been known to produce galactose-alpha1,4
      galactose-beta1,4-glucose ceramide (Gb3) that play an important role in the
      mucosal immune response. The regulation of Gb3 is important to prevent tissue
      damage causing shiga like toxin. Epigallocatechin-3-gallate (EGCG) has been
      studied as anti-carcinogenic, anti-oxidant, anti-angiogenic, and anti-viral
      activities, and anti-diabetic. However, little is known between the expressions
      of Gb3 on IECs. The aim of this study was to examine the inhibitory effect of
      EGCG, a major ingredient of green tea, on Gb3 production via mitogen-activated
      protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB) in the TNF-alpha
      stimulated human colon epithelial cells, HT29. To investigate how Gb3 is
      regulated, ceramide glucosyltransferase (CGT), lactosylceramide synthase (GalT2),
      and Gb3 synthase (GalT6) were analyzed by RT-PCR in HT 29 cells exposed to TNF
      alpha in the presence or absence of EGCG. EGCG dose-dependently manner, inhibits
      TNF-alpha induced Gb3 expression by blocking in both the MAPKs and NF-kappaB
      pathways in HT29 cells. TNF-alpha enhanced CGT, GalT2 and GalT6 mRNA levels and
      EGCG suppressed the level of these enzymes enhanced by TNF-alpha treatment.

PMID- 16100444
TI  - Fasting plasma glucose cutoff value for the prediction of future diabetes
      development: a study of middle-aged Koreans in a health promotion center.
AB  - We determined optimal fasting plasma glucose (FPG) cutoff values predictive of
      future diabetes development in a group of middle-aged Koreans who visited a
      health promotion center. The medical records of 2,964 subjects, who attended the
      Health Promotion Center in 1998 and 2003, were examined. Subjects were classified
      into four groups according to their baseline FPG values (Group 1:FPG <5.0 mM/L;
      Group 2: 5.0< or =FPG <5.6 mM/L; Group 3: 5.6< or =FPG <6.1 mM/L; Group 4: 6.1<
      or =FPG <7.0 mM/L). No significant difference was observed between Group 1 and
      Group 2 in terms of diabetes incidence. However, incidence in Group 3 was
      significantly higher than that in Group 1 [hazards ratio 4.88 (1.65-14.41),
      p=0.004] and the hazards ratio in Group 4 for diabetes was 36.91 (13.11-103.61),
      p<0.001, versus Group 1. Receiver operator characteristics curve analysis showed
      that an FPG of 5.97 mM/L represents the lower limit and gives the best
      combination of sensitivity and specificity. Our data shows that the risk of
      future diabetes development started to increase below an FPG of 6.1 mM/L and
      suggests the importance of efforts to modify diabetes development risk factors at
      lower impaired fasting glucose levels.

PMID- 16100445
TI  - Murine model of buckwheat allergy by intragastric sensitization with fresh
      buckwheat flour extract.
AB  - Food allergies affect about 4% of the Korean population, and buckwheat allergy is
      one of the most severe food allergies in Korea. The purpose of the present study
      was to develop a murine model of IgE-mediated buckwheat hypersensitivity induced
      by intragastric sensitization. Young female C3H/HeJ mice were sensitized and
      challenged intragastricly with fresh buckwheat flour (1, 5, 25 mg/dose of
      proteins) mixed in cholera toxin, followed by intragastric challenge.
      Anaphylactic reactions, antigen-specific antibodies, splenocytes proliferation
      assays and cytokine productions were evaluated. Oral buckwheat challenges of
      sensitized mice provoked anaphylactic reactions such as severe scratch,
      perioral/periorbital swellings, or decreased activity. Reactions were associated
      with elevated levels of buckwheatspecific IgE antibodies. Splenocytes from
      buckwheat allergic mice exhibited significantly greater proliferative responses
      to buckwheat than non-allergic mice. Buckwheat-stimulated IL-4, IL-5, and INF
      gamma productions were associated with elevated levels of buckwheat-specific IgE
      in sensitized mice. In this model, 1 mg and 5 mg dose of sensitization produced
      almost the same degree of Th2-directed immune response, however, a 25 mg dose
      showed blunted antibody responses. In conclusion, we developed IgE-mediated
      buckwheat allergy by intragastric sensitization and challenge, and this model
      could provide a good tool for future studies.

PMID- 16100446
TI  - Chestnut as a food allergen: identification of major allergens.
AB  - To evaluate the clinical significance of chestnut as a food allergen in Korea,
      skin prick test and ELISA were done in 1,738 patients with respiratory allergies.
      To identify the IgE binding components, IgE-immunoblotting, 2D IgE-immunoblotting
      and MALDITOF were performed. To observe the effects of digestive enzymes and a
      boiling treatment, simulated gastric fluid (SGF) and simulated intestinal fluids
      (SIF) were incubated with chestnut extracts, and IgE-immunoblotting were then
      repeated. Skin prick test revealed that 56 (3.2%) patients showed more than 2+ of
      allergen to histamine ratio to chestnut. Among the 21 IgE binding components, 9
      bands were found in more than 50% of the sera tested and the 24 kDa protein had
      the highest binding intensity. The amino acid sequence of the 24 kDa protein (pI
      6.3) had homology with legume protein of oak tree. SGF, SIF and boiling treatment
      were able to suppress the IgE binding components. In conclusion, chestnut
      ingestion was shown to induce IgE mediated responses with a 3.2% sensitization
      rate. Twenty one IgE binding components and one new allergen (the 24 kDa protein)
      were identified. Digestive enzymes and boiling treatment were able to decrease
      the allergenic potency.

PMID- 16100447
TI  - Proteomic analysis of differently expressed proteins in a mouse model for
      allergic asthma.
AB  - Allergic asthma is associated with persistent functional and structural changes
      in the airways and involves many different cell types. Many proteins involved in
      allergic asthma have been identified individually, but complete protein profiles
      (proteome) have not yet been reported. Here we have used a differential proteome
      mapping strategy to identify tissue proteins that are differentially expressed in
      mice with allergic asthma and in normal mice. Mouse lung tissue proteins were
      separated using two-dimensional gel electrophoresis over a pH range between 4 and
      7, digested, and then analyzed by matrix-assisted laser desorption/ionization
      time of flight mass spectrometry (MS). The proteins were identified using
      automated MS data acquisition. The resulting data were searched against a protein
      database using an internal Mascot search routine. This approach identified 15
      proteins that were differentially expressed in the lungs of mice with allergic
      asthma and normal mice. All 15 proteins were identified by MS, and 9 could be
      linked to asthma-related symptoms, oxidation, or tissue remodeling. Our data
      suggest that these proteins may prove useful as surrogate biomarkers for
      quantitatively monitoring disease state progression or response to therapy.

PMID- 16100448
TI  - Effect of high dose inhaled glucocorticoids on quality of life in patients with
      moderate to severe asthma.
AB  - Asthma is a chronic disorder that can place considerable restrictions on the
      physical, emotional, and social aspects of the lives of patients. Inhaled
      glucocorticoids (GCs) are the most effective controller therapy. The purpose of
      this study was to evaluate the effect of inhaled GCs on quality of life in
      patients with moderate to severe asthma. Patients completed the asthma quality of
      life questionnaire (AQLQ) and pulmonary function test at baseline and after 4 wks
      treatment of GCs. We enrolled 60 patients who had reversibility in FEV1 after 200
      microgram of albuterol of 15% or more and/or positive methacholine provocation
      test, and initial FEV1% predicted less than 80%. All patients received inhaled
      GCs (fluticasone propionate 1,000 microgram/day) for 4 wks. The score of AQLQ was
      significantly improved following inhaled GCs (overall 51.9+/-14.3 vs. 67.5+/
      12.1, p<0.05). The change from day 1 to day 28 in FEV1 following inhaled GCs was
      diversely ranged from -21.0% to 126.8%. The improvement of score of AQLQ was not
      different between at baseline and after treatment of GCs according to asthma
      severity and GCs responsiveness. Quality of life was improved after inhaled GCs
      regardless of asthma severity and GCs responsiveness in patients with moderate to
      severe asthma.

PMID- 16100449
TI  - Comparison of clinical efficacy of Newfactan versus Surfacten for the treatment
      of respiratory distress syndrome in the newborn infants.
AB  - Newfactan is a domestically developed, bovine lung-derived, semi-synthetic
      surfactant. The aim of this study was to compare the clinical efficacy of
      Newfactan with that of Surfacten in the treatment of respiratory distress
      syndrome (RDS). Newfactan or Surfacten was randomly allocated to 492 newborn
      infants who were diagnosed as RDS and required surfactant instillation in four
      participating hospitals. The comparisons were made individually in two subsets of
      infants by birth weight (<1,500 g group [n=253] and > or =1,500 g group [n=239]).
      Short-term responses to surfactant and acute complications, such as the total
      doses of surfactant instilled, response type, extubation rate, ventilator
      settings, changes in respiratory parameters, air leak, patent ductus arteriosus,
      pulmonary hemorrhage, and intraventricular hemorrhage, and mortality during the
      96 hr after surfactant instillation were measured. Long-term outcome and
      complications, such as total duration of intubation, bronchopulmonary dysplasia
      and periventricular leukomalacia, and ultimate mortality were measured. There
      were no significant differences in demographic and perinatal variables, shortterm
      responses to surfactant and acute complications, and long-term outcome and
      complications between Newfactan and Surfacten in both birth weight groups. We
      concluded that Newfactan was comparable to Surfacten in the clinical efficacy in
      the treatment of RDS in both birth weight groups.

PMID- 16100450
TI  - A pilot study of bortezomib in Korean patients with relapsed or refractory
      myeloma.
AB  - Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had
      therapeutic activity in multiple myeloma. However, there was no data about the
      feasibility of bortezomib in Korean patients. We performed a pilot study of
      bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice
      weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median
      age of patients was 59 yr. All patients previously received VAD (vincristine,
      doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients
      previously received alkylator-containing chemotherapy and 4 patients, autologous
      stem cell transplantation. Bortezomib monotherapy resulted in 3 partial
      remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient
      who had no response to bortezomib monotherapy experienced partial remission after
      addition of dexamethasone to bortezomib. The most common serious toxicity was
      thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral
      neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led
      to discontinuation of bortezomib in 1 patient. There was no treatment related
      mortality. Overall, bortezomib seems to be effective and feasible. Conduction of
      larger clinical studies on Korean patients is necessary to characterize clinical
      efficacy and safety of bortezomib more precisely.

PMID- 16100451
TI  - Investigation of the bovine leukemia virus proviral DNA in human leukemias and
      lung cancers in Korea.
AB  - The bovine leukemia virus (BLV) is the causative agent of enzootic bovine
      leucosis. This study investigated the presence of the BLV in leukemia (179 acute
      lymphoblastic leukemia, 292 acute myeloid leukemia and 46 chronic myelogenous
      leukemia cases) and 162 lung cancer patients (139 adenocarcinoma, 23 squamous
      cell carcinoma) to determine if the BLV is a causative organism of leukemia and
      lung cancer in Koreans. A BLV infection was confirmed in human cells by PCR using
      a BLV-8 primer combination. All 517 cases of human leukemia and 162 lung cancer
      were negative for a PCR of the BLV proviral DNA. In conclusion, although meat has
      been imported from BLV endemic areas, the BLV infection does not appear to be the
      cause of human leukemia or lung cancer in Koreans. These results can be used as a
      control for further studies on the BLV in Koreans.

PMID- 16100452
TI  - Polymorphism of matrix metalloproteinase-3 promoter gene as a risk factor for
      coronary artery lesions in Kawasaki disease.
AB  - Kawasaki disease (KD) is a major cause of acquired coronary artery diseases in
      childhood. The serum levels of matrix metalloproteinase (MMP)-3 and MMP-9 in KD
      have been reported to be significantly higher than other diseases. Several
      studies have demonstrated that MMP-3 5A/6A polymorphism and MMP-9 C-1562T
      polymorphism modify each transcriptional activity in allele specific manner. We
      hypothesized that these polymorphisms may play a role as a risk factor for
      development of coronary artery lesions (CAL) in KD. Eighty-three patients,
      diagnosed with KD in Cheju National University Hospital from January 2000 to
      February 2004, were divided into two groups according to the presence of CAL.
      Genotyping of MMP-3 and MMP-9 gene polymorphisms were determined by restriction
      fragment length polymorphism. With regard to MMP-3 gene polymorphism, the KD with
      CAL group had a higher frequency of 6A/6A genotype than control group (p=0.0127)
      and the KD without CAL group (p=0.0036). However, no significant differences in
      the allele and genotype distributions of the MMP-9 polymorphism were observed.
      These findings suggest that MMP-3 6A/6A genotype may be an independent risk
      factor for CAL formation in KD.

PMID- 16100453
TI  - Effects of magnesium sulfate on supraceliac aortic unclamping in experimental
      dogs.
AB  - Intravascular administration of magnesium (Mg) causes vasodilation and increases
      renal blood flow. The aim of this study was to investigate the renal effect of Mg
      following unclamping of the supraceliac aorta. Mongrels were divided into two
      groups, control (group C, n=7) and Mg group (group Mg, n=7). In group Mg, 30
      mg/kg MgSO4 was injected as a bolus immediately prior to unclamping the
      supraceliac aorta and thereafter as an infusion (10 mg/kg/hr). The group C
      received an equivalent volume of saline solution. Systemic hemodynamics, renal
      artery blood flow, renal cortical blood flow (RCBF), renal vascular resistance,
      and renal function were compared. Following the aortic unclamping, cardiac output
      and RCBF were less attenuated, and the systemic and renal vascular resistance was
      elevated to a lesser degree in the group Mg compared to the group C. There was no
      significant difference in the plasma renin activity, serum creatinine and
      Cystatin-C between the two groups. The present study shows that Mg infusion
      improves systemic hemodynamics and RCBF after aortic unclamping. However, we did
      not observe any improvement in renal function when Mg was administered after
      supraceliac aortic unclamping.

PMID- 16100454
TI  - Bi-weekly chemotherapy of paclitaxel and cisplatin in patients with metastatic or
      recurrent esophageal cancer.
AB  - Although various combinations of chemotherapy regimens have been tried for
      patients with esophageal cancer, their duration of survival is extremely poor. In
      this study, we investigated the safety and clinical efficacy of paclitaxel and
      cisplatin chemotherapy in metastatic or recurrent esophageal cancer. 32 patients
      enrolled in this study and the median age was 60 yr. Of all the 32, 28 patients
      (88%) had been treated previously, 22 of them with chemotherapy or radiation
      therapy. All patients in the study received biweekly paclitaxel (90 mg/m(2))
      followed by cisplatin (50 mg/m(2)). One patient (3%) responded completely, and 12
      patients (38%) showed a partial response; in 9 patients (28%) the disease
      remained stable, and in 10 patients (31%) it progressed. The objective response
      rate was 41%. The median duration of response was 4.8 months, and the median
      overall survival in all patients was 7 months. The 1-yr and 2-yr survival rates
      were 28.1% and 7.1%, respectively. Grade 3 or 4 of neutropenia and anemia were
      observed in 6 (19%) and 5 (16%) patients, respectively. The major non-hematologic
      toxicity was fatigue, but most of them could manageable. In conclusion, biweekly
      paclitaxel and cisplatin is effective in patients with metastatic or recurrent
      esophageal cancer.

PMID- 16100455
TI  - Cutoff values of preoperative s-CEA levels for predicting survivals after
      curative resection of colorectal cancer.
AB  - Serum carcinoembryonic antigen (s-CEA) is used to detect recurrence and predict
      prognosis in colorectal cancer. However, the cutoff values of s-CEA for prognosis
      have not been determined. We therefore tried to determine the preoperative s-CEA
      levels predictive of survivals in colorectal cancer patients. We retrospectively
      analyzed the medical records of 989 patients who underwent curative resection for
      colorectal cancer between July 1990 and December 1997, with a mean followup of 46
      months (range, 3-129 months). When patients were divided into four subgroups with
      the cutoff values of s-CEA at 3,6, and 17 ng/mL, their 5-yr diseasefree survival
      rates were 85.3% (<3.0 ng/mL), 70.0% (3-6 ng/mL), 64.2% (6-17 ng/mL), and 55.2%
      (>17 ng/mL) (p<0.001). Multivariate analysis showed that factors predictive of
      survival included age (p=0.028), tumor stage (p<0.001), cell differentiation
      (p=0.016), and gross type (p=0.007), location (p=0.003) and preoperative s-CEA
      (p<0.001). Using the above-described cutoff levels, a significant difference in
      survival was observed only in patients with stage III tumors (p=0.007) when
      analyses were performed by stage. We can suggest the new cutoff values of s-CEA
      used in the present study.

PMID- 16100456
TI  - Expression and regulation of latent TGF-beta binding protein-1 transcripts and
      their splice variants in human glomerular endothelial cells.
AB  - Latent transforming growth factor (TGF)-beta-binding protein (LTBP) is required
      for the assembly, secretion, matrix association, and activation of latent TGF
      beta complex. To elucidate the cell specific expression of the genes of LTBP-1
      and their splice variants and the factors that regulate the gene expression, we
      cultured primary human glomerular endothelial cells (HGEC) under different
      conditions. Basal expression of LTBP-1 mRNA was suppressed in HGEC compared to WI
      38 human embryonic lung fibroblasts. High glucose, H(2)O(2), and TGF-beta1
      upregulated and vascular endothelial growth factor (VEGF) further downregulated
      LTBP-1 mRNA in HGEC. RT-PCR with a primer set for LTBP-1S produced many clones
      but no clone was gained with a primer set for LTBP-1L. Of 12 clones selected
      randomly, Sca I mapping and DNA sequencing revealed that only one was LTBP-1S and
      all the others were LTBP-1Sdelta53. TGF-beta1, but not high glucose, H(2)O(2) or
      VEGF, tended to increase LTBP-1Sdelta53 mRNA. In conclusion, HGEC express LTBP-1
      mRNA which is suppressed at basal state but upregulated by high glucose,
      H(2)O(2), and TGF-beta1 and downregulated by VEGF. Major splice variant of LTBP-1
      in HGEC was LTBP-1S 53. Modification of LTBP-1S 53 gene in HGEC may abrogate
      fibrotic action of TGF-beta1 but this requires confirmation.

PMID- 16100457
TI  - Epstein-Barr virus and p16INK4A methylation in squamous cell carcinoma and
      precancerous lesions of the cervix uteri.
AB  - Methylation of p16 is an important mechanism in cervical carcinogenesis. However,
      the relationship between cervical squamous cell carcinoma (SCC) and Epstein-Barr
      virus (EBV) remains controversial. Here, we explored whether EBV infection and/or
      p16 gene inactivation would play any role in cervical carcinogenesis. Eighty-two
      specimens included 41 invasive SCCs, 30 cervical intraepithelial neoplasm (CIN;
      CIN 1, 11 cases, CIN II, 3 cases, CIN III 16 cases) and 11 nonneoplastic
      cervices. EBV was detected by polymerase chain reaction (PCR) for EBNA-1 and in
      situ hybridization for EBER-1. The p16 methylation-status and the expression of
      p16 protein were studied by methylation-specific PCR and immunohistochemistry,
      respectively. The materials were divided into four groups: 1) nonneoplastic
      cervices, 2) CIN I, 3) CIN II-III and 4) invasive SCCs. p16 methylation and p16
      immunoexpressions increased in CIN and invasive SCCs than nonneoplastic tissue.
      p16-methylation and p16-immunoreactivities were higher in the EBV-positive group
      (p=0.009, p<0.001) than in the EBV-negative group. EBV was detected more
      frequently in CIN and SCCs than nonneoplastic cervices. In conclusion, a
      correlation between p16 methylation, p16 immunoreactivity and the detection of
      EBV strongly suggested that the cooperation of EBV and p16 gene may play a
      synergic effect on cell cycle deregulation.

PMID- 16100458
TI  - The usefulness of CDX-2 for differentiating primary and metastatic ovarian
      carcinoma: an immunohistochemical study using a tissue microarray.
AB  - Distinguishing primary ovarian carcinoma from metastatic carcinoma to the ovary
      is often difficult by histologic examination alone. Recently an
      immunohistochemical marker CDX-2 was found to be of considerable diagnostic value
      in establishing the gastrointestinal origin of metastatic tumors. The aim of this
      study was to determine whether CDX-2 can distinguish between these malignancies.
      Paraffin-embedded tissue sections from 57 primary ovarian tumors and 40
      metastatic tumors to the ovary were immunostained for CDX-2, and results were
      compared to the ancillary immunohistochemical results for CK7/CK20, CEA, CA125,
      and her-2/neu. CDX-2 immunoreactivity was observed in most of metastatic
      carcinomas with colorectal (91%) and appendiceal (100%) origin, however CDX-2 was
      negative in all primary ovarian carcinomas, except for the mucinous subtype.
      Almost all primary ovarian carcinomas including the mucinous subtype showed
      diffuse and strong immunoexpression for CK7. CEA and CA125 were mainly found in
      metastatic and primary ovarian carcinoma, respectively. Her-2/neu overexpression
      was only noted in a small proportion of primary and metastatic ovarian
      carcinomas. These results suggest that CDX-2 is very useful immunohistochemical
      marker for distinguishing metastatic colorectal carcinoma to the ovary from
      primary ovarian carcinoma, including the mucinous subtype. Furthermore,
      combination with CDX-2 and CK7 strengthen the differential diagnosis between
      these tumors.

PMID- 16100459
TI  - Expression and modulation of LL-37 in normal human keratinocytes, HaCaT cells,
      and inflammatory skin diseases.
AB  - Defensins and cathelicidins (LL-37) are major antimicrobial peptides (AMPs) of
      the innate immune system of the human skin. In normal non-inflamed skin these
      peptides are negligible, but their expression can be markedly increased in
      inflammatory skin disease such as psoriasis. We designed this study to identify
      the expressions of LL-37 in normal human keratinocyte (NHK) and HaCaT cells after
      exposure to stimulants and to investigate difference of LL-37 expression
      accompanied with cell differentiation status, and come to understand difference
      of susceptibility to infection in atopic dermatitis and psoriasis. Expressions of
      LL-37 in NHKs and HaCaT cells were evaluated by using RT-PCR, Western blotting,
      and immunohistochemical (IHC) staining at 6, 12, and 24 hr post stimulation after
      exposure to Ultraviolet B irradiation and lipopolysaccharide. And expression of
      LL-37 in skin biopsy specimens from patients with atopic dermatitis and psoriasis
      was determined by immunohistochemical analysis. In time-sequential analyses of LL
      37 expression revealed that LL-37 was expressed in NHKs, but not in HaCaT cells.
      IHC analysis confirmed the presence of abundant LL-37 in the epidermis of
      psoriasis. Therefore we deduced that expression of LL-37 is affected by UV
      irradiation, bacterial infection, and status of cell differentiation.

PMID- 16100460
TI  - Rising incidence of hip fracture in Gwangju City and Chonnam Province, Korea.
AB  - The purpose of study was to determine the incidence of hip fracture in 2001, to
      compare this with that of 1991, and to identify possible causes of change.
      Patients aged 50 yr or more living in Gwangju City and Chonnam Province, Korea,
      and who sustained a fracture of the hip during 2001 were investigated. Only
      patients who were admitted to hospitals for primary treatment of the first hip
      fracture were selected. There were 1,152 patients. A comparison of fracture
      incidences for 1991 and 2001 showed considerable increase during the 10-yr
      period. The total annual number of hip fractures rose from 247 in 1991 to 1,152
      in 2001 and the fracture incidence also increased remarkably from 3.3 persons per
      10,000 population in 1991 to 13.3 in 2001, representing a 4-fold increase over 10
      yr. The reasons for this rising trend of hip fracture were not fully explained.
      However, an increase in the elderly population, an increase in osteoporosis, and
      an increase in injurious falls could partly account for the observed increase.

PMID- 16100461
TI  - Cervical facet joint injections in the neck and shoulder pain.
AB  - The effects from cervical facet joint injections in those patients who have been
      complaining cervical zygapophyseal joint pain were compared. The patients were
      diagnosed originally as myofascial pain syndrome (MPS), cervical herniated
      nucleus pulposus (HNP), and whiplash-associated disorders (WAD). Patients with
      the zygapophyseal joints pain of C5-6 and C6-7 were classified by their pain
      origin as MPS, HNP, and WAD. All patients had been undergone cervical
      zygapophyseal joints injections with the mixture of lidocaine and triamcinolone
      unilaterally or bilaterally through the posterior approach under C-arm imaging
      guide. The therapeutic effects were compared with reduction of numeric rating
      scale (NRS) of pain before and immediately after blockade and symptom-free
      periods in each group after 12 months. Symptom durations before injections were
      16.1+/-9.6, 4.6+/-1.9 and 4.1+/-1.1 months in each MPS, HNP, and WAD groups. The
      reductions of NRS immediately after the blockade among the three groups were not
      different. However, the symptom-free duration after blockade lasted longer in the
      HNP group than the other two groups. In patients with cervical zygapophyseal pain
      syndromes, the analgesic effect from cervical facet joint blocks lasted longer in
      cervical HNP than MPS or WAD.

PMID- 16100462
TI  - The role of inducible nitric oxide synthase following spinal cord injury in rat.
AB  - Acute spinal cord injury (SCI) is two-step process that first involves the
      primary mechanical injury and then the secondary injury is induced by various
      biochemical reactions. Apoptosis is one of secondary SCI mechanisms and it is
      thought to play an important role for the delayed neuronal injury. The enhanced
      formation of nitric oxide (NO) via inducible nitric oxide synthase (iNOS) has
      been implicated in the pathogenesis of apoptosis in SCI. The level of .iNOS mRNA
      peaked at 6 hr after SCI and it declined until 72 hr after SCI in a rat model.
      Double-immunofluorescence staining revealed that iNOS positive cells were stained
      for ED-1, synaptophysin, GFAP, and oligodendrocyte marker. The terminal
      deoxynucleotidyl-transferase-mediated dUDP-biotin nick end-labeling (TUNEL)
      positive cell count was higher for the 72 hr post-SCI group than for the 24 hr
      post-SCI group. This cell count was also higher going in the caudal direction
      than in the rostral direction from the epicenter, and especially for the 72 hr
      group. Treatment with a selective iNOS inhibitor resulted in the reduction of
      TUNEL-positive cells at the lesion site. These findings suggest that nitric oxide
      generated by the iNOS of macrophages, neurons, oligodentrocytes, and astrocytes
      plays an important role for the acute secondary SCI that results from apoptotic
      cell death.

PMID- 16100463
TI  - A novel missense mutation of doublecortin: mutation analysis of Korean patients
      with subcortical band heterotopia.
AB  - The neuronal migration disorders, X-linked lissencephaly syndrome (XLIS) and
      subcortical band heterotopia (SBH), also called "double cortex", have been linked
      to missense, nonsense, aberrant splicing, deletion, and insertion mutations in
      doublecortin (DCX) in families and sporadic cases. Most DCX mutations identified
      to date are located in two evolutionarily conserved domains. We performed
      mutation analysis of DCX in two Korean patients with SBH. The SBH patients had
      mild to moderate developmental delays, drug-resistant generalized seizures, and
      diffuse thick SBH upon brain MRI. Sequence analysis of the DCX coding region in
      Patient 1 revealed a c.386 C>T change in exon 3. The sequence variation results
      in a serine to leucine amino acid change at position 129 (S129L), which has not
      been found in other family members of Patient 1 or in a large panel of 120
      control X-chromosomes. We report here a novel c.386 C>T mutation of DCX that is
      responsible for SBH.

PMID- 16100464
TI  - Intrathoracic aneurysm of the right subclavian artery presenting with hoarseness:
      a case report.
AB  - Intrathoracic segment of the subclavian artery is an unusual location for
      peripheral arterial aneurysms. They are normally caused by atherosclerosis,
      medial degeneration, trauma, and infection. We report a case of a patient with
      right subclavian artery aneurysm presenting with hoarseness. Chest radiograph
      demonstrated a superior mediastinal mass. Laryngoscopy showed a fixed right vocal
      cord. By chest computed tomography, magnetic resonance imaging, and angiography,
      preoperative diagnosis was established as a saccular aneurysm with afferent loop
      and efferent loop. Patient underwent complete resection of the aneurysm followed
      by endto-end anastomosis via median sternotomy. Postoperative pathology was
      consistent with an atherosclerotic aneurysm filled with thrombus. After surgical
      operation, hoarseness is still continued.

PMID- 16100465
TI  - Hypereosinophilia presenting as eosinophilic vasculitis and multiple peripheral
      artery occlusions without organ involvement.
AB  - We report here a case with hypereosinophilia and peripheral artery occlusion. A
      32-yr-old Korean woman presented to us with lower extremity swelling and pain.
      Angiography revealed that multiple lower extremity arteries were occlusive. The
      biopsy specimen showed perivascular and periadnexal dense eosinophilic
      infiltration in dermis and subcutaneous adipose tissue. Laboratory investigations
      revealed a persistent hypereosinophilia. She was prescribed prednisolone 60 mg
      daily. Her skin lesion and pain were improved and the eosinophil count was
      dramatically decreased. After discharge, eosinophil count gradually increased
      again. Cyanosis and pain of her fingers recurred. She had been treated with
      cyclophosphamide pulse therapy. Her eosinophilia was decreased, but the cyanosis
      and tingling sense were progressive. The extremity arterial stenoses were
      slightly progressed. Skin biopsy showed perivascular eosinophilic infiltration in
      the dermis and CD40 ligand (CD40L) positive eosinophilic infiltration. The serum
      TNF-alpah was markedly increased. These results suggest that CD40L (a member of
      TNF-alpah superfamily) could play a role in the inflammatory processes when
      eosinophil infiltration and activation are observed. We prescribed prednisolone,
      cyclophosphamide, clopidogrel, cilostazol, beraprost and nifedipine, and she was
      discharged.

PMID- 16100466
TI  - Colonoscopic diagnosis of appendiceal intussusception: a case report.
AB  - Intussusception of the appendix is an uncommon condition and the diagnosis is
      rarely made preoperatively. Intussusception of the appendix may mimic a
      neoplastic lesion. Colonoscopy is a valuable tool for diagnosis of the
      appendiceal intussusception. A 17-yr-old female admitted with repeated abdominal
      pain, nausea, vomiting and febrile sensation. We diagnosed as appendiceal
      intussusception by colonoscopy, which showed a polypoid tumor (about 1.5 cm) in
      the cecum. This sessile polypoid mass looks like foreskin or glans. We present
      colonoscopic finding of appendiceal intussusception and review the literature.

PMID- 16100467
TI  - Cutaneous metastasis of choriocarcinoma: a case report.
AB  - Choriocarcinoma is one of the malignant tumors of trophoblastic cells
      characterized by the secretion of human chorionic gonadotrophin (hCG) (1-3).
      Cutaneous metastasis is a rare presentation of choriocarcinoma but a poor
      prognostic sign because it is associated only with widespread disease (3-5). A 52
      yr-old female complaining of dyspnea for 2 months, presented with fingertip sized
      erythematous nodules on the left side of the neck and the right side of the upper
      back of 1 month duraton. She has suffered from Behcet's disease since 1999.
      Microscopic examination of a nodule of upper back demonstrated biphasic pattern
      of cytotrophoblasts and hCG-positive syncytiotrophoblasts, and the typical
      histologic features of choriocarcinoma. She was referred to the gynecological
      oncology department. After 17 cycles of combination chemotherapy, the serum hCG
      level has fallen from 700,000 to under 2.0 mIU/mL and the skin lesions have
      almost disappeared. However, after 3 months, total abdominal hysterectomy and
      bilateral salpingo-oophorectomy were performed due to elevated serum hCG level
      (4,447.7 mIU/mL), and she is scheduled to receive post-operative adjuvant
      chemotherapy.

PMID- 16100468
TI  - Extraskeletal Ewing's sarcoma of the hard palate.
AB  - Extraskeletal Ewing's sarcoma (EES) is a rare soft tissue tumor morphologically
      indistinguishable from the more common Ewing's sarcoma of bone. We report a case
      of EES arising in the hard palate of 34-yr-old male patient. Microscopically, the
      monotonous small round cells without neuronal differentiation showed membranous
      positive immunoreactivity for MIC2/CD99 and vimentin. Ultrastructurally, the
      tumor cells showed a few intracytoplasmic organelles without evidence of
      neurosecretory granules or neurofilaments. The EWS-FLI1 chimeric gene was
      identified using the nested reverse transcriptase-polymerase chain reaction.

PMID- 16100469
TI  - Delirium and extrapyramidal symptoms due to a lithium-olanzapine combination
      therapy: a case report.
AB  - We report an elderly patient who developed severe delirium and extrapyramidal
      signs after initiation of lithium-olanzapine combination. On hospital admission,
      serum levels of lithium were found to be 3.0 mM/L which were far above toxic
      level. Immediate discontinuation of both drugs resulted in complete resolution of
      most of the symptoms except for perioral dyskinesia which persisted for three
      more months. We critically discussed the differential diagnosis of lithium
      intoxication and assessed confounding factors which induce delirium and
      extrapyramidal signs related with combination therapy of lithium and olanzapine.

PMID- 16100470
TI  - Macrophage activation syndrome in a child with systemic juvenile rheumatoid
      arthritis.
AB  - Macrophage activation syndrome (MAS) is a rare and potentially fatal complication
      of rheumatic disorders in children. We describe a 13-month-old boy in whom MAS
      developed as a complication of systemic juvenile rheumatoid arthritis (S-JRA). He
      suffered from fever and generalized rash followed by multiple joints swelling for
      four months before admission. Physical examination revealed cervical
      lymphadenopathy and hepatosplenomegaly. Laboratory findings were: abnormal liver
      enzymes, increased triglyceride and ferritin levels, coagulopathies resembling
      disseminated intravascular coagulation, anemia and thrombocytopenia. Hyperplasia
      of hemophagocytic macrophages was remarkable in his bone marrow.
      Methylprednisolone and cyclosporin therapy resulted in clinical and laboratory
      improvements. This is the third case of MAS associated with S-JRA in Koreans, and
      the first one, in which hemophagocytic macrophages were proven in bone marrow.

PMID- 16100471
TI  - Cerebral infarction in IgG multiple myeloma with hyperviscosity.
AB  - Cerebral infarction is an uncommon complication in multiple myeloma with
      hyperviscosity. Serum hyperviscosity may cause a variety of clinical
      manifestations including bleeding from mucosal membranes, congestive heart
      failure, retinopathy, and various neurologic deficits. These manifestations have
      been attributed to the presence of large quantities of asymmetrical molecules of
      high molecular weight in the serum. We recently experienced a case of multiple
      myeloma with acute cerebral infarction, which caused by hyperviscosity, as an
      initial manifestation in IgG multiple myeloma, and reviewed the relevant
      literature of myeloma presenting with the stroke. A 68-yr-old woman abruptly
      developed hypesthesia and monoplegia in the left leg. The stroke confirmed by the
      brain MRI and MR angiography, which revealed acute infarction at the right
      anterior cerebral artery territory. On admission, routine blood tests showed a
      slight decrease in hemoglobin and a marked increase in erythrocyte sedimentation
      rate. Peripheral blood smear, serum protein electrophoresis, serum visocity, and
      bone marrow aspiration showed that she had IgG multiple myeloma with
      hyperviscosity. She was treated by chemotherapy with cyclophosphamide and
      discharged with the improved clinical condition.

PMID- 16100472
TI  - Indigo carmine for the selective endoscopic intervertebral nuclectomy.
AB  - This study was undertaken to prove that the selectively infiltrated parts of
      nucleus pulposus with indigo carmine was degenerated parts of nucleus pulposus.
      This study was done, between August and October 2002, in 5 patients, who received
      endoscopic discectomy, due to intervertebral disc herniation. Discogram was done
      with mixture of indigo carmine and radioactive dye. Blue discolored part was
      removed through endoscope, and small undiscolored part was removed together for
      the control. The two parts were stained with hematoxylin and eosin and compared
      under the microscope. Undiscolored part was normal nucleus pulposus, composed of
      chondrocytes with a matrix of type II collagen and proteoglycan, mainly aggrecan.
      However, in discolored part, slits with destruction of collagen fiber array and
      ingrowth of vessel and nerve were observed. Using indigo carmine in endoscopic
      discectomy gives us selective removal of degenerated disc.

PMID- 16100473
TI  - Impact of Chlamydia trachomatis and HPV infection among sexually active teenage
      girls in Upper Silesia, Poland.

PMID- 16100474
TI  - Focally increased activity in the lateral aspect of the mid cervical spine on
      bone scintigraphy is almost always benign in nature.
AB  - OBJECTIVES: Abnormal bone scan findings in the spine are often nonspecific. The
      confidence level for the differential diagnosis between metastases and benign or
      degenerative changes may vary depending on their appearance, location or
      intensity. The recognition of a specific pattern for certain benign conditions
      and its subcategorization will increase the credibility of bone scan
      interpretation while retaining a high level of sensitivity. We report one such
      finding, focally increased activity on the lateral side of the cervical spine on
      the posterior view, most common at the C3-C5 level ("mid-cervical-lateral
      focus"). METHODS: Of 481 patients with various cancers who had at least 2 whole
      body bone scans, 6 months or more apart, 41 patients were judged to show this
      characteristic "mid-cervical-lateral-focus" on at least one scan. Final diagnosis
      (metastasis vs. benign) for each "mid-cervical-lateral-focus" was made based on
      clinical grounds and serial bone scans. RESULTS: The bone scan showed definite
      multiple metastases in 15 patients, and the differential diagnosis for the "mid
      cervical-lateral-focus" was already clinically irrelevant in these patients.
      Nevertheless, the "mid-cervical-lateral-focus" was finally judged to be benign in
      14 of these 15 patients and in all remaining 26 patients without other obvious
      metastases. The only "mid-cervical-lateral-focus" judged to be a metastatic focus
      was not only clinically redundant, but also the most intense among all the "mid
      cervical-lateral-foci." in this series (too intense to be interpreted as benign).
      CONCLUSION: The typical "mid-cervical-lateral-focus" pattern is extremely
      unlikely to represent metastases (virtually 0% in patients without other obvious
      metastases). This knowledge helps exclude metastases on bone scans.

PMID- 16100475
TI  - Stress-induced right ventricular ischemia in recurrent pulmonary outflow stenosis
      in repaired tetralogy of fallot.
AB  - Radionuclide uptake by the right ventricle during myocardial perfusion imaging is
      minimal compared with the left ventricular myocardium and is not given much
      importance. However, right ventricular hypertrophy from pressure or volume
      overload may increase right ventricular radiotracer uptake and demonstrate
      reversible stress-induced perfusion abnormalities in the presence of normal
      coronary arteries. We report a case of right ventricular ischemia secondary to
      right ventricular hypertrophy from recurrent right ventricular outflow tract
      stenosis in a patient with repaired tetralogy of Fallot. Advances in the
      management of congenital heart disease have led to more patients surviving to
      adulthood. These patients subsequently present to cardiologists in adulthood with
      sequelae or complications arising from previous surgery undertaken during
      childhood.

PMID- 16100476
TI  - Evaluating benign and malignant musculoskeletal lesions with radionuclide
      angiography and SPECT using Tc-99m MIBI.
AB  - PURPOSE: The purpose of this study was to evaluate the use of radionuclide
      angiography and single photon emission computed tomography (SPECT) using Tc-99m
      hexakis-2-methoxyisobutylisonitrile (Tc-99m MIBI) for analyzing musculoskeletal
      lesions. MATERIALS AND METHODS: Radionuclide angiography and SPECT using Tc-99m
      MIBI were performed in 36 patients with various soft tissue and bone pathologies
      (18 benign and 18 malignant lesions). The ratio of the counts of the lesion to
      that of the contralateral normal area was calculated from the region of interest
      drawn on the MIBI scan. The MIBI-uptake ratio was calculated using SPECT and the
      MIBI-perfusion index was calculated using radionuclide angiography. RESULTS: The
      MIBI-uptake ratio in malignant lesions (4.80 +/- 4.43) was significantly higher
      (P < 0.05) than that in benign lesions (1.83+/-2.48). The sensitivity,
      specificity, accuracy, positive predictive value, and negative predictive value
      of the MIBI-uptake ratio for malignant lesions were 72%, 83%, 78%, 81%, and 75%,
      respectively. The MIBI-perfusion index in malignant lesions (17.68 +/- 21.19) was
      significantly higher (P < 0.05) than that in benign lesions (2.25 +/- 2.56). The
      sensitivity, specificity, accuracy, positive predictive value, and negative
      predictive value of the MIBI-perfusion index for malignant lesions were 87%, 75%,
      81%, 77%, and 86%, respectively. CONCLUSIONS: The MIBI-uptake ratio and MIBI
      perfusion index using Tc-99m MIBI can yield important additional information with
      which to differentiate musculoskeletal lesions.

PMID- 16100477
TI  - Proteus syndrome: a rare cause of hemihypertrophy and macrodactyly on bone
      scanning.
AB  - Proteus syndrome is a rare, sporadic genetic disorder characterized by overgrowth
      of multiple different tissues in a mosaic pattern. It is associated with
      connective tissue nevi, epidermal nevi, disproportionate overgrowth of multiple
      tissues, vascular malformations, characteristic tumors, and specific facial
      anomalies. Joseph Merrick, popularly known as the Elephant Man, is now believed
      to have suffered from Proteus syndrome. A case of Proteus syndrome and associated
      findings on bone scintigraphy are presented.

PMID- 16100478
TI  - Detection of bone marrow metastases by FDG-PET and missed by bone scintigraphy in
      widespread melanoma.
AB  - The optimal management of patients with melanoma requires accurate imaging
      techniques that can screen the entire body for metastases. One of the most used
      tests for this purpose is bone scintigraphy. PET has been reported to be more
      sensitive than bone scintigraphy in some malignancies. In our case, FDG-PET was
      also superior to bone scintigraphy in detecting the extent of skeletal disease in
      a patient with melanoma. This is likely the result of the fact that metastasis to
      bone marrow may not result in bone reaction in certain conditions and therefore
      bone scans may remain negative despite skeletal involvement.

PMID- 16100479
TI  - Osteoblastic osteosarcoma of the mandible: findings on Tc-99m HMDP bone and Ga-67
      citrate scintigraphy.
AB  - A 25-year-old woman presented with a disturbance in the opening of her mouth 5
      months before admission. On admission, painful swelling of the right preauricular
      region was revealed. Computed tomography (CT) demonstrated a soft tissue density
      mass around the right condylar process of the mandible. Tc-99m hydroxymethylene
      diphosphonate (HMDP) bone scintigraphy and Ga-67 citrate scintigraphy showed avid
      uptake in the mass. The tumor was histologically identified as an osteoblastic
      osteosarcoma of the right mandible. There are few reports of Ga-67 citrate
      scintigraphy findings of osteoblastic osteosarcoma of the mandible. The
      accumulation patterns on Tc-99m HMDP bone scintigraphy and Ga-67 citrate
      scintigraphy are possibly characteristic of osteoblastic osteosarcoma of the
      mandible.

PMID- 16100480
TI  - Ewing sarcoma of the rib with normal blood flow and blood pool imagings on a 3
      phase bone scan.
AB  - Ewing sarcoma is the second most common pediatric malignant bone tumor. It
      usually presents as a hot spot on a 3-phase bone scan as a result of increased
      vascularity of the tumor and new bone formation. However, aggressive Ewing
      sarcoma can also appear as a cold lesion. We present the features of a Ewing
      sarcoma of the rib on a 3-phase bone scan in a child who was being investigated
      for rib fracture after trauma.

PMID- 16100481
TI  - Solitary plasmacytoma of bone: an unusual cause of severe sacral pain in a young
      man.
AB  - A 35-year-old man presented with insidious onset of severe sacral pain. Plain
      radiography, computed tomography, and magnetic resonance imaging revealed a
      large, locally invasive mass within the sacrum. Skeletal scintigraphy showed
      marked hyperemia and minimal peripheral osteoblastic activity of the sacral mass.
      An F-18 FDG PET study was performed for further assessment and clinical staging.
      The mass demonstrated high glucose avidity consistent with a high-grade tumor.
      Histologic examination confirmed the lesion to be a plasmacytoma. Solitary
      plasmacytoma of bone occurs predominantly in older patients involving the axial
      skeleton. This case is interesting in view of the large dimension, sacral
      involvement, the young age of the patient, and the appearance of this lesion
      across multiple imaging modalities.

PMID- 16100482
TI  - Lymphangitic spread of breast carcinoma: scintigraphic pattern with chest x-ray
      and computed tomography correlation.
AB  - Lymphangitic spread of metastases has distinct patterns on pulmonary scintigraphy
      and radiographic imaging. A 43-year-old woman with metastatic breast cancer
      presented with shortness of breath. Symptomatology was studied with ventilation
      and perfusion (V/Q) scintigraphy, chest radiograph, and computed tomography (CT).
      The scintigraphic pattern is consistent with prior descriptions of lymphangitic
      spread of tumor. The chest x-ray and CT were both performed within the prior 2
      months and were confirmatory.

PMID- 16100483
TI  - F-18 FDG uptake associated with Elastofibroma dorsi.
AB  - A patient with a history of colon carcinoma and computed tomography (CT) evidence
      suggestive of a liver metastasis underwent an F-18 FDG PET scan. The PET scan
      confirmed a metastasis in the left lobe of the liver. The study also demonstrated
      bilateral symmetric uptake involving the inferior subscapular regions.
      Correlation with the previous CT showed this to correspond to bilateral
      elastofibroma dorsi, which had been prospectively reported on the CT.
      Elastofibroma dorsi is a rare benign mass consisting of fibroelastic tissue and
      fat. It has been previously described on PET, CT, ultrasound, and magnetic
      resonance imaging (MRI). On CT, the masses are of soft tissue density, similar to
      adjacent musculature, and may contain linear areas of low density secondary to
      fat. On MRI, elastofibroma dorsi has been shown to have variable enhancement,
      which may reflect increased vascularity of the lesion. In this case, the masses
      demonstrated low-grade diffuse F-18 FDG uptake.

PMID- 16100484
TI  - Superior vena cava and right atrial thrombus detected on lung perfusion
      scintigraphy.
AB  - Ventilation and perfusion scanning is still used as the first modality for
      evaluating pulmonary embolism in pregnant and renal failure patients and those
      who are allergic to radiographic contrast. Hot spots in the right atrial area on
      perfusion scan are the result of the presence of thrombi. These thrombi are of 2
      varieties. One type is a free-floating thrombus, which needs emergency
      thrombectomy, and another type is thrombus formation in the atria, predisposed by
      the presence of catheters. We report a study showing essentially normal perfusion
      but intense tracer uptake in the superior vena cava and right atrium. Noncontrast
      computed tomography confirmed the thrombus.

PMID- 16100485
TI  - Renal scintigraphy unraveled the diagnostic dilemma of antenatal hydronephrotic
      solitary kidney-crossed renal ectopia.
AB  - On antenatal ultrasound assessment, an apparently solitary hydronephrotic kidney
      was identified, confirmed on postnatal ultrasound examination. More detailed
      postnatal investigations revealed the diagnosis of crossed renal ectopia.

PMID- 16100486
TI  - Difference in filtered-back projection and iterative reconstruction in a patient
      with increased splanchnic uptake.
AB  - We performed a dual isotope, gated adenosine stress myocardial perfusion study on
      a 44-year-old man. Using filtered-back projection, images showed an inferior wall
      defect. However, intense liver uptake during adenosine stress was suspected to
      inaccurately cause diminished inferior wall counts. The patient has end-stage
      renal disease, diabetes mellitus, and hypertension. The excessive hepatic uptake
      was noted on planar rotating images and is likely related (at least in part) to
      reduced renal uptake (not shown subsequently). Using iterative reconstruction,
      the inferior cardiac defect was markedly reduced. The patient subsequently
      underwent surgery without complication.

PMID- 16100487
TI  - Positron emission tomography in Dyke-Davidoff-Masson syndrome.
AB  - Dyke-Davidoff-Masson syndrome is clinically characterized by hemiparesis,
      hemiplegia, seizures, mental retardation, and facial asymmetry secondary to
      congenital or early childhood vascular insult. A 21-year-old man with Dyke
      Davidoff-Masson syndrome presented with uncontrolled seizures. The authors
      present the magnetic resonance (MR) and positron emission tomography (PET)
      findings of this syndrome.

PMID- 16100488
TI  - Pancreatic neuroendocrine tumor with portal vein tumor thrombus: PET
      demonstration.
AB  - Tumor thrombus differentiates itself from bland thrombus by its contrast
      enhancement features on cross-sectional imaging and its intense uptake of F-18
      FDG on PET as a result of its hypervascularity and high metabolic neoplastic
      activity. This PET pattern has been reported in cases of renal cell carcinoma and
      adrenal cortical carcinoma with invasion of the inferior vena cava. Tumor
      thrombus may involve the superior mesenteric and portal veins in patients with
      abdominal or pelvic malignancy. The author presents a case of recurrent
      pancreatic neuroendocrine tumor with mesenteric and portal venous thrombotic
      invasion imaged by PET and computed tomography.

PMID- 16100489
TI  - Ectopic functioning thyroid tissue in the thyroglossal duct detected by
      radionuclide imaging.
AB  - A 49-year-old man with a clinical diagnosis of Graves' disease was referred for a
      thyroid scan and radioactive ablation of the gland. Tc-99m pertechnetate scan
      revealed a diffuse toxic goiter and radiotracer concentration in the thyroglossal
      duct. He was given 10 mCi of I-131 orally as treatment of thyrotoxicosis. Repeat
      scanning of the anterior neck 2 days later revealed concentration of radioiodine
      in the diffusely enlarged gland and the thyroglossal duct as found on the Tc-99m
      pertechnetate scan, thus confirming the presence of functioning thyroid tissue in
      the thyroglossal duct.

PMID- 16100490
TI  - Epiphrenic diverticulum: potential pitfall in thyroid cancer iodine-131
      scintigraphy.
AB  - Unusual features of iodine-131 uptake during thyroid cancer scintigraphy may lead
      to a false-positive diagnosis of residual or recurrent malignancy and associated
      metastasis. Radiographic or cross-sectional imaging correlation should help to
      differentiate truly functioning thyroid lesions from physiological or artifactual
      tracer accumulation. The authors present a case of iodine-131 mediastinal uptake
      from an esophageal epiphrenic diverticulum.

PMID- 16100491
TI  - Mediastinal histoplasmosis: F-18 FDG PET and CT findings simulating malignant
      disease.
AB  - We describe the computed tomography and F-18 FDG PET findings of a patient with
      extensive mediastinal nodal enlargement resulting from histoplasmosis. This
      patient with known metastatic melanoma presenting for restaging was initially
      considered to have widespread mediastinal and cervical metastases on the basis of
      the imaging findings. Bronchoalveolar lavage fluid and transbronchial lymph node
      biopsy were consistent with histoplasmosis. The imaging findings improved after
      treatment with antifungal medication. A relatively small area of pulmonary
      involvement proved to be the clue in the imaging studies that the disease was
      inflammatory rather than neoplastic.

PMID- 16100492
TI  - Focal nodular hyperplasia (FNH): a potential cause of false-positive positron
      emission tomography.
AB  - Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) has been
      proven to be a useful tool in the differential diagnosis of liver tumors. Focal
      nodular hyperplasia (FNH) is an uncommon benign liver lesion, which can be
      difficult to differentiate from other benign and malignant liver pathologies. FDG
      PET imaging usually shows uptake similar or even decreased compared to that of
      the normal liver. We describe a hypermetabolic FNH lesion in a patient with a
      history of breast cancer. Computed tomography scan, ultrasonography (US), and
      magnetic resonance imaging were negative. The lesion was resected, and histologic
      findings were consistent with FNH.

PMID- 16100493
TI  - A pitfall of FDG-PET image interpretation: accumulation of FDG in the dependent
      area of the urinary bladder after bladder irrigation--the usefulness of the prone
      position.
AB  - In F-18 FDG PET studies, retrograde irrigation of the urinary bladder is usually
      used to reduce the interference with physiological urinary accumulation of F-18
      FDG in patients with possible pelvic lesions. A 34-year-old female who had
      recently been diagnosed with cervical cancer had an F-18 FDG-PET scan performed
      for whole-body evaluation. The bladder was irrigated with physiological saline
      and filled with 200 mL of irrigation fluid through a 3-way balloon catheter
      inserted before the scan. Two areas with high FDG accumulation were noted in the
      posterior pelvis. Tumor invasion or metastasis could not be ruled out. Additional
      focal imaging of the pelvis was performed with the patient in the prone position.
      The lesion on the left side of the patient was still noted, whereas the lesion on
      the right had disappeared, which proved that it was a false-positive lesion.
      Great caution is required when assessing imaging results to avoid misdiagnosis in
      patients after bladder irrigation.

PMID- 16100494
TI  - Current readings in nuclear medicine.

PMID- 16100496
TI  - Environment of Care (EC).

PMID- 16100497
TI  - Consumers' food preferences.

PMID- 16100498
TI  - Eating disorder and depressive symptoms in urban high school girls from different
      ethnic backgrounds.
AB  - This study examined ethnic group differences in the rates of eating disorder
      symptoms (EDS) and depressive disorder symptoms (DDS) with respect to ethnic
      identity, relative body weight, and abnormal eating behaviors among adolescent
      girls. A district-wide sample of high school girls (N = 1445) from different
      ethnic backgrounds was surveyed. EDS were assessed with the Eating Attitudes Test
      26, abnormal eating behaviors with the Eating Behaviors Survey, and DDS with the
      Short Mood and Feelings Questionnaire. Two dimensions of ethnic identity, ethnic
      identity achievement and other group orientation, were assessed with Multi-Group
      Ethnic Identity Measure. Hispanic and non-Hispanic white girls had the highest
      and African-American (AA) and Caribbean girls the lowest rates of EDS. Asian
      girls reported the highest and AA girls the lowest rates of DDS. Early dieting
      was associated with EDS and DDS in Caribbean, non-Hispanic white, and mixed
      background girls. Relative body weight was related to EDS in all ethnic groups
      except in non-Hispanic white and mixed background girls. The authors did not find
      an effect of ethnic identity achievement on psychopathology, but there was an
      effect of other group orientation on both EDS and DDS. Clinicians should inquire
      about EDS and DDS in girls of all ethnic groups. Prevention efforts to delay
      unsupervised dieting may protect adolescent girls from the development of EDS and
      DDS.

PMID- 16100499
TI  - Parental emotional support and subsequent internalizing and externalizing
      problems among children.
AB  - This study examined the association between early emotional support provided by
      parents and child internalizing and externalizing problems, using a nationally
      representative, longitudinal sample of 1361 children. Parental emotional support
      was assessed using the Home Observation for the Measurement of the Environment,
      incorporating both parent report and interviewer observation. We found that,
      controlling for child externalizing problems at age 6 years, parental emotional
      support at age 6 years was negatively related to child externalizing problems at
      age 8 years. A developmental model that assessed the timing of the emergence of
      this relationship was then analyzed by including parental emotional support at
      ages 2, 4, and 6 years as predictors of child externalizing problems at age 8
      years. The developmental model suggested that less parental emotional support as
      early as age 2 years is associated with later externalizing problems in children.
      This study discusses the importance of very early parental emotional support in
      promoting positive child development.

PMID- 16100500
TI  - Incidence of brain creatine transporter deficiency in males with developmental
      delay referred for brain magnetic resonance imaging.
AB  - Several case reports describe children with global developmental delay who have
      brain creatine deficiency, where the deficiency was due to a lack of creatine
      transport into the brain or altered creatine synthesis. The purpose of this study
      was to determine what percentage of males with developmental delay referred for
      brain magnetic resonance imaging (MRI) at the authors' institution in a 12-month
      period was found to have brain creatine deficiency due to a defect in the
      creatine transporter gene. In the authors' facility, single voxel proton magnetic
      resonance spectroscopy (MRS) is routinely performed on any male child age 2 to 18
      years with a history of language and/or developmental delay referred for a brain
      MRI. Charts for the 12-month time period were retrospectively reviewed. Fourteen
      subjects met inclusion criteria for global developmental delay. Two of the 14
      patients had brain creatine deficiency on MRS. In the remaining 12, other
      structural and white matter abnormalities were identified. This study suggests
      that brain creatine deficiency is an important consideration in the differential
      diagnosis of males with global developmental delay referred for brain MRI; brain
      MRS should be considered in such cases.

PMID- 16100501
TI  - Parental perceptions of infant vulnerability in a preterm sample: prediction from
      maternal adaptation to parenthood during the neonatal period.
AB  - The present longitudinal study of African-American mothers of preterm infants
      tested the hypothesis that the quality of maternal adaptation to parenthood
      before infant discharge from the hospital is predictive of maternal perceptions
      of infant vulnerability later in the infant's first year. As hypothesized,
      perceptions of infant vulnerability at 3 to 4 months of infant corrected age were
      predicted by two theoretically relevant measures of maternal adaptation in the
      neonatal period: mothers' perceptions of their neonates as lethargic and
      unresponsive to mothers' bids and by low maternal self-efficacy beliefs about
      feeding the infant. Neonatally obtained maternal self-inefficacy beliefs about
      their ability to feed the infant in particular proved to be quite robust in
      predicting mothers' later perceptions of infant vulnerability. Findings
      collectively suggest that careful attention to the manner in which mothers of
      preterm infants adapt to parenthood, even before infant hospital discharge, can
      help clinicians identify mothers at particularly high risk of developing
      perceptions of infant vulnerability later in the infant's first year.
      Implications for intervention are discussed.

PMID- 16100502
TI  - Prevalence and early identification of language delays among at-risk three year
      olds.
AB  - The aims of this study were fourfold: to document the prevalence of language
      delays in a sample of at-risk 3 year olds; to assess the effectiveness of a home
      visiting program in preventing early language delays; to determine how often
      parents, pediatric providers, and home visitors identified early language delays;
      and to assess the effectiveness of a home visiting program in improving early
      identification of language delays. The Preschool Language Scale, Third Edition
      (PLS-3) was administered to 513 at-risk 3 year olds participating in a randomized
      trial of home visiting services. Families randomized to home visiting were
      expected to receive weekly to quarterly visits throughout the 3 years of this
      study. The content of home visits included teaching parents about child
      development, role-modeling parenting skills, and linking families to a medical
      home. Identification of delays was measured using structured parent interviews
      and review of primary care and home visiting records. At age 3 years, 10% of
      children had severe language delays, defined as scoring >or=2 SD below the
      national mean on the PLS-3, whereas 49% scored >or=1 SD below the national mean.
      No differences in prevalence were seen between children who did and did not
      receive home visiting. Among children with severe delays, 42% were identified by
      parents, 33% by pediatric providers, and 24% by home visitors. Among children
      with any delays, 24% were identified by parents, 25% by pediatric providers, and
      17% by home visitors. No differences in rates of identification were seen between
      children who did and did not receive home visiting. Thus, while language delays
      were highly prevalent among these at-risk children, rates of identification were
      low, even among children with severe delays. Home visiting was not effective in
      either preventing language delays or improving early identification. This
      suggests that pediatric providers and home visiting programs need to reexamine
      their approaches to recognizing and intervening with early language delays.

PMID- 16100503
TI  - Early identification of language delays--are we there yet?

PMID- 16100506
TI  - A toddler with hair fascination.

PMID- 16100507
TI  - The ADHD and sleep conundrum: a review.
AB  - The relationship between attention-deficit hyperactivity disorder (ADHD) and
      sleep is a complex one that poses many challenges in clinical practice. Recent
      studies have helped to elucidate the nature of the brain mechanisms and
      neuromodulator systems underlying the theoretical associations among sleepiness,
      arousal, and attention. Studies of sleep disturbances in children with academic
      and behavioral problems have also underscored the role that primary sleep
      disorders such as obstructive sleep apnea hypopnea syndrome play in the clinical
      presentation of symptoms of inattention and behavioral dysregulation. In
      addition, new methodologies used in examining sleep and sleep patterns in
      children diagnosed with ADHD have shed further light on the prevalence, type,
      risk factors for, and impact of sleep disturbances in these children. The
      following discussion of the multilevel relationships among sleep quality and
      quantity, neurobehavioral functioning, and the clinical syndrome of ADHD expands
      on previous reviews of the literature and synthesizes what is currently known
      about the interaction of sleep and attention/arousal in children to propose
      possible underlying mechanisms, integrate more recent findings, and highlight
      important areas for future study. In addition, guidelines are provided for a
      clinical approach to evaluation and management of children with ADHD and sleep
      problems.

PMID- 16100508
TI  - Diagnosis to function: classification for children and youths.
AB  - This article provides an overview of a newly approved World Health Organization
      framework and classification system for human functioning. The International
      Classification of Functioning, Disability, and Health (ICF) identifies dimensions
      of human functioning and describes a common language for clinical practice,
      research, and policy development across disciplines and service systems. This
      presentation highlights the development of a version of the ICF for children and
      youths (ICF-CY) and its potential utility in developmental and behavioral
      pediatrics. Clinical, research, and policy dimensions are described. Limitations
      related to scope and clarity of the framework are also outlined. The article
      proposes that serious consideration be given the ICF-CY as an integrated system
      to clarify constructs, improve communication, and encourage coordination of
      health services for children and youths.

PMID- 16100511
TI  - A role for lateral hypothalamic orexin neurons in reward seeking.
AB  - The lateral hypothalamus is a brain region historically implicated in reward and
      motivation, but the identity of the neurotransmitters involved are unknown. The
      orexins (or hypocretins) are neuropeptides recently identified as
      neurotransmitters in lateral hypothalamus neurons. Although knockout and
      transgenic overexpression studies have implicated orexin neurons in arousal and
      sleep, these cells also project to reward-associated brain regions, including the
      nucleus accumbens and ventral tegmental area. This indicates a possible role for
      these neurons in reward function and motivation, consistent with previous studies
      implicating these neurons in feeding. Here we show that activation of lateral
      hypothalamus orexin neurons is strongly linked to preferences for cues associated
      with drug and food reward. In addition, we show that chemical activation of
      lateral hypothalamus orexin neurons reinstates an extinguished drug-seeking
      behaviour. This reinstatement effect was completely blocked by prior
      administration of an orexin A antagonist. Moreover, administration of the orexin
      A peptide directly into the ventral tegmental area also reinstated drug-seeking.
      These data reveal a new role for lateral hypothalamus orexin neurons in reward
      seeking, drug relapse and addiction.

PMID- 16100512
TI  - Protein kinase D regulates vesicular transport by phosphorylating and activating
      phosphatidylinositol-4 kinase IIIbeta at the Golgi complex.
AB  - Protein kinase D (PKD) regulates the fission of vesicles originating from the
      trans-Golgi network. We show that phosphatidylinositol 4-kinase IIIbeta
      (PI4KIIIbeta) - a key player in the structure and function of the Golgi complex -
      is a physiological substrate of PKD. Of the three PKD isoforms, only PKD1 and
      PKD2 phosphorylated PI4KIIIbeta at a motif that is highly conserved from yeast to
      humans. PKD-mediated phosphorylation stimulated lipid kinase activity of
      PI4KIIIbeta and enhanced vesicular stomatitis virus G-protein transport to the
      plasma membrane. The identification of PI4KIIIbeta as one of the PKD substrates
      should help to reveal the molecular events that enable transport-carrier
      formation.

PMID- 16100513
TI  - Load-dependent kinetics of myosin-V can explain its high processivity.
AB  - Recent studies provide strong evidence that single myosin class V molecules
      transport vesicles and organelles processively along F-actin, taking several 36
      nm steps, 'hand over hand', for each diffusional encounter. The mechanisms
      regulating myosin-V's processivity remain unknown. Here, we have used an optical
      tweezers-based transducer to measure the effect of load on the mechanical
      interactions between rabbit skeletal F-actin and a single head of mouse brain
      myosin-V, which produces its working stroke in two phases. We found that the
      lifetimes of the first phase of the working stroke changed exponentially and
      about 10-fold over a range of pushing and pulling forces of +/- 1.5 pN. Stiffness
      measurements suggest that intramolecular forces could approach 3.6 pN when both
      heads are bound to F-actin, in which case extrapolation would predict the
      detachment kinetics of the front head to slow down 50-fold and the kinetics of
      the rear head to accelerate respectively. This synchronizing effect on the chemo
      mechanical cycles of the heads increases the probability of the trail head
      detaching first and causes a strong increase in the number of forward steps per
      diffusional encounter over a system with no strain dependence.

PMID- 16100514
TI  - Engineering metal-impurity nanodefects for low-cost solar cells.
AB  - As the demand for high-quality solar-cell feedstock exceeds supply and drives
      prices upwards, cheaper but dirtier alternative feedstock materials are being
      developed. Successful use of these alternative feedstocks requires that one
      rigorously control the deleterious effects of the more abundant metallic
      impurities. In this study, we demonstrate how metal nanodefect engineering can be
      used to reduce the electrical activity of metallic impurities, resulting in
      dramatic enhancements of performance even in heavily contaminated solar-cell
      material. Highly sensitive synchrotron-based measurements directly confirm that
      the spatial and size distributions of metal nanodefects regulate the minority
      carrier diffusion length, a key parameter for determining the actual performance
      of solar-cell devices. By engineering the distributions of metal-impurity
      nanodefects in a controlled fashion, the minority-carrier diffusion length can be
      increased by up to a factor of four, indicating that the use of lower-quality
      feedstocks with proper controls may be a viable alternative to producing cost
      effective solar cells.

PMID- 16100515
TI  - Three-dimensionality of field-induced magnetism in a high-temperature
      superconductor.
AB  - Many physical properties of high-temperature superconductors are two-dimensional
      phenomena derived from their square-planar CuO2 building blocks. This is
      especially true of the magnetism from the copper ions. As mobile charge carriers
      enter the CuO2 layers, the antiferromagnetism of the parent insulators, where
      each copper spin is antiparallel to its nearest neighbours, evolves into a
      fluctuating state where the spins show tendencies towards magnetic order of a
      longer periodicity. For certain charge-carrier densities, quantum fluctuations
      are sufficiently suppressed to yield static long-period order, and external
      magnetic fields also induce such order. Here we show that, in contrast to the
      chemically controlled order in superconducting samples, the field-induced order
      in these same samples is actually three-dimensional, implying significant
      magnetic linkage between the CuO2 planes. The results are important because they
      show that there are three-dimensional magnetic couplings that survive into the
      superconducting state, and coexist with the crucial inter-layer couplings
      responsible for three-dimensional superconductivity. Both types of coupling will
      straighten the vortex lines, implying that we have finally established a direct
      link between technical superconductivity, which requires zero electrical
      resistance in an applied magnetic field and depends on vortex dynamics, and the
      underlying antiferromagnetism of the cuprates.

PMID- 16100516
TI  - Novel electrical switching behaviour and logic in carbon nanotube Y-junctions.
AB  - Carbon-nanotube-based electronics offers significant potential as a nanoscale
      alternative to silicon-based devices for molecular electronics technologies.
      Here, we show evidence for a dramatic electrical switching behaviour in a Y
      junction carbon-nanotube morphology. We observe an abrupt modulation of the
      current from an on- to an off-state, presumably mediated by defects and the
      topology of the junction. The mutual interaction of the electron currents in the
      three branches of the Y-junction is shown to be the basis for a potentially new
      logic device. This is the first time that such switching and logic
      functionalities have been experimentally demonstrated in Y-junction nanotubes
      without the need for an external gate. A class of nanoelectronic architecture and
      functionality, which extends well beyond conventional field-effect transistor
      technologies, is now possible.

PMID- 16100517
TI  - The physics and neurobiology of magnetoreception.
AB  - Diverse animals can detect magnetic fields but little is known about how they do
      so. Three main hypotheses of magnetic field perception have been proposed.
      Electrosensitive marine fish might detect the Earth's field through
      electromagnetic induction, but direct evidence that induction underlies
      magnetoreception in such fish has not been obtained. Studies in other animals
      have provided evidence that is consistent with two other mechanisms: biogenic
      magnetite and chemical reactions that are modulated by weak magnetic fields.
      Despite recent advances, however, magnetoreceptors have not been identified with
      certainty in any animal, and the mode of transduction for the magnetic sense
      remains unknown.

PMID- 16100518
TI  - The neuroscience of grasping.
AB  - People have always been fascinated by the exquisite precision and flexibility of
      the human hand. When hand meets object, we confront the overlapping worlds of
      sensorimotor and cognitive functions. We reach for objects, grasp and lift them,
      manipulate them and use them to act on other objects. This review examines one of
      these actions--grasping. Recent research in behavioural neuroscience,
      neuroimaging and electrophysiology has the potential to reveal where in the brain
      the process of grasping is organized, but has yet to address several questions
      about the sensorimotor transformations that relate to the control of the hands.

PMID- 16100519
TI  - Role of aromatase inhibitors in breast cancer.
AB  - Primarily, the role of the aromatase inhibitors has been investigated in
      postmenopausal women with breast cancer, although it is also now being assessed
      in premenopausal patients following ovarian ablation/suppression. Aromatase
      inhibitors markedly suppress endogenous oestrogens without directly interacting
      with oestrogen receptors, and thus have a different mechanism of action to the
      antioestrogen, tamoxifen. The inhibitors may be divided into subgroups according
      to their structure (steroidal and nonsteroidal), and there appears to be a lack
      of cross-resistance between the classes of aromatase inhibitors enabling them to
      be used sequentially and potentially to prolong endocrine hormone therapy. In
      addition, with increased efficacy and favourable safety and tolerability
      profiles, the aromatase inhibitors are starting to challenge tamoxifen as first
      choice endocrine treatment in a number of settings. Potential differences in side
      effect profiles may appear between the steroidal and nonsteroidal aromatase
      inhibitors when used in long-term settings. Thus, it has been suggested that the
      steroidal agents have favourable end organ effects; for example, the steroidal
      inhibitor, exemestane, has minimal negative effects on bone and lipid metabolism
      in animal and clinical studies. This paper provides an overview of the current
      and future roles of aromatase inhibitors for breast cancer treatment.

PMID- 16100520
TI  - Potential use of COX-2-aromatase inhibitor combinations in breast cancer.
AB  - Cyclooxygenase-2 (COX-2) is overexpressed in several epithelial tumours,
      including breast cancer. Cyclooxygenase-2-positive tumours tend to be larger,
      higher grade, node-positive and HER-2/neu-positive. High COX-2 expression is
      associated with poor prognosis. Cyclooxygenase-2 inhibition reduces the incidence
      of tumours in animal models, inhibits the development of invasive cancer in
      colorectal cancer and reduces the frequency of polyps in familial adenomatous
      polyposis (FAP). These effects may be as a result of increased apoptosis, reduced
      angiogenesis and/or proliferation. Studies of COX-2 inhibitors in breast cancer
      are underway both alone and in combination with other agents. There is evidence
      to suggest that combining COX-2 inhibitors with aromatase inhibitors, growth
      factor receptor blockers, or chemo- or radiotherapy may be particularly
      effective. Preliminary results from combination therapy with celecoxib and
      exemestane in postmenopausal women with advanced breast cancer showed that the
      combination increased the time to recurrence. Up to 80% of ductal carcinomas in
      situ (DCISs) express COX-2, therefore COX-2 inhibition may be of particular use
      in this situation. Cyclooxygenase-2 expression correlates strongly with
      expression of HER-2/neu. As aromatase inhibitors appear particularly effective in
      patients with HER-2/neu-positive tumours, the combination of aromatase inhibitors
      and COX-2 inhibitors may be particularly useful in both DCIS and invasive cancer.

PMID- 16100521
TI  - Bone loss and the aromatase inhibitors.
AB  - The increasing use of systemic adjuvant therapies has considerably improved the
      prognosis from early breast cancer. However, some of these therapies affect bone
      metabolism, resulting in osteoporosis. Aromatase inhibitors lower circulating
      oestrogen levels to almost unrecordable levels in postmenopausal women,
      predisposing them to bone loss with an increase in fracture risk. Ongoing
      clinical trials are favouring the use of the aromatase inhibitors over tamoxifen
      and this may advocate greater use of these drugs in the future. Strategies for
      the identification and management of treatment-induced bone loss are currently
      being defined.

PMID- 16100522
TI  - The effects of aromatase inhibitors on lipids and thrombosis.
AB  - Oestrogen is known to influence blood lipid levels and though its
      cardioprotective effects are less clear than once thought, there remains concern
      that reduction of oestrogen levels during hormonal treatment for breast cancer
      may have an adverse effect on cardiovascular risk. While tamoxifen has been shown
      to improve lipid profiles, the aromatase inhibitors have a very different mode of
      action and do not possess the oestrogen-agonistic effects of tamoxifen. At
      present, there are few data on the effects of these agents on lipid profiles.
      Available data are mixed, but suggest that the different aromatase inhibitors
      have different effects on lipid profiles. Some studies show anastrozole as
      generally having little effect on lipids, while others have indicated adverse
      effects on lipid profiles/increased hypercholesterolaemia. Letrozole has been
      associated with adverse effects on lipid profiles in some studies, including BIG
      1-98, but short-term data from randomised trials do not show increased
      cardiovascular morbidity. By contrast, exemestane, which has been studied in
      slightly more detail, may either have little effect or may be associated with
      slightly improved lipid profiles. In general, the changes have been small and are
      likely to be of little relevance in women with advanced breast cancer, but if
      these agents come to be used in early breast cancer, their impact on lipid
      profiles may become more important. Many studies are currently underway with the
      aromatase inhibitors, with safety assessments including monitoring lipid levels.
      The results of these studies are keenly awaited.

PMID- 16100523
TI  - Sequencing of aromatase inhibitors.
AB  - Since the development of the third-generation aromatase inhibitors (AIs),
      anastrozole, letrozole and exemestane, these agents have been the subject of
      intensive research to determine their optimal use in advanced breast cancer. Not
      only have they replaced progestins in second-line therapy and challenged the role
      of tamoxifen in first-line, but there is also evidence for a lack of cross
      resistance between the steroidal and nonsteroidal AIs, meaning that they may be
      used in sequence to obtain prolonged clinical benefit. Many questions remain,
      however, as to the best sequence of the two types of AIs and of the other
      available agents, including tamoxifen and fulvestrant, in different patient
      groups.

PMID- 16100524
TI  - The inhibitory effect of alendronate, a nitrogen-containing bisphosphonate on the
      PI3K-Akt-NFkappaB pathway in osteosarcoma cells.
AB  - 1 Bisphosphonates are inhibitors of tumor cell growth as well as of bone
      resorption by inducing cell apoptosis. However, little is known regarding the
      mechanisms by which the drug induces cell apoptosis. The aim of the present study
      was to determine the effect of alendronate, one of the nitrogen-containing
      bisphosphonates on the phoshoinositide 3-kinase (PI3K)-Akt-NFkappaB pathway, the
      major cell survival pathway. 2 The PI3K-Akt-NFkappaB pathway was activated in the
      osteosarcoma cell line MG-63 treated with tumor necrosis factor-alpha or insulin.
      Saos-2 was also used in some experiments. This was assessed by the production of
      phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)), increased PI3K
      activity, phosphorylation of Akt at serine 473 and threonine 308, increase in
      activity of the inhibitor of nuclear factor kappaB (IkappaB) kinase (IKK) and
      finally phosphorylation of IkappaB and its subsequent degradation. 3 Pretreatment
      with alendronate at 100 microM for 24 h prior to the stimulation with tumor
      necrosis factor-alpha or insulin partially inhibited the IkappaB phosphorylation
      and degradation. These events were more clearly observed in the presence of
      inhibitors of proteasomes, which are responsible for the degradation of IkappaB.
      The drug also partially inhibited the activity of IKK, but almost fully inhibited
      the phosphorylation of Akt and the production of PtdIns(3,4,5)P(3). 4 The
      inhibitory effect of alendronate on IkappaB phosphorylation and degradation was
      not attenuated by the exogenous addition of geranylgeraniol to replenish the
      cytosolic isoprenyl lipid substrate. 5 The present findings demonstrate that
      alendronate inhibited the PI3K-Akt-NFkappaB cell survival pathway at the point of
      PI3K activation, thus indicating the presence of new targets of alendronate.

PMID- 16100525
TI  - Neutrophils and the kallikrein-kinin system in proteinase-activated receptor 4
      mediated inflammation in rodents.
AB  - 1 We evaluated a potential role for proteinase-activated receptor 4 (PAR(4)) in a
      rodent paw inflammation model, with a focus on two main features of inflammation:
      (1) oedema and (2) granulocyte recruitment. 2 A PAR(4) antagonist (Pepducin P4pal
      10; palmitoyl-SGRRYGHALR-NH(2)) reduced both the oedema and granulocyte
      recruitment induced by a localized administration of carrageenan in the rat hind
      paw, pointing to a key role for PAR(4) in this inflammation model. 3 Further,
      intraplantar injection in the mouse hind paw of a PAR(4) agonist (AYPGKF-NH(2)),
      but not its standard PAR(4)-inactive peptide control (YAPGKF-NH(2)), caused an
      inflammatory reaction characterized by oedema (increased paw thickness) and
      granulocyte recruitment (increased paw myeloperoxidase activity). The PAR(4)
      agonist-induced effects were inhibited in mice pretreated with pepducin P4pal10.
      4 These PAR(4) agonist-mediated effects were not affected by pretreatment with
      inhibitors of either NO production or prostaglandin release (L-NAME and
      indomethacin, respectively). 5 However, selective immuno-depletion of neutrophils
      significantly reduced PAR(4) agonist-induced oedema formation. 6 Moreover, AYPGKF
      NH(2)-induced oedema was also reduced by pretreatment with either a kinin B(2)
      receptor antagonist (icatibant) or a tissue or plasma kallikrein inhibitor
      (FE999024 and FE999026, respectively), but not with a kinin B(1) receptor
      antagonist (SSR240612). 7 We conclude: (1) that PAR(4) plays an important role in
      the inflammatory response as it mediates some of the hallmarks of inflammation
      and (2) that PAR(4)-mediated oedema is dependent on the recruitment of
      neutrophils and components of the kallikrein-kinin system.

PMID- 16100526
TI  - The regulation of veratridine-stimulated electrogenic ion transport in mouse
      colon by neuropeptide Y (NPY), Y1 and Y2 receptors.
AB  - 1 Neuropeptide Y (NPY) is a prominent enteric neuropeptide with prolonged
      antisecretory effects in mammalian intestine. Veratridine depolarises neurons
      consequently causing epithelial anion secretion across mouse colon mucosa. Our
      aim was to characterise functionally, veratridine-stimulated mucosal responses
      and to determine the roles for NPY, Y(1), and Y(2) receptors in modulating these
      neurogenic effects. 2 Colon mucosae (with intact submucous innervation) from wild
      type mice (+/+) and knockouts lacking either NPY (NPY-/-), Y(1)-/- or Y(2)-/-
      were placed in Ussing chambers and voltage clamped at 0 mV. Veratridine
      stimulated short-circuit current (I(sc)) responses in +/+, Y(1) or Y(2)
      antagonist pretreated +/+ colon, Y(1)-/- and NPY-/- colon were insensitive to
      cholinergic blockade by atropine (At; 1 microM) and hexamethonium (Hex; 10
      microM). Tetrodotoxin (TTX, 100 nM) abolished veratridine responses, but had no
      effect upon carbachol (CCh) or vasoactive intestinal polypeptide (VIP)-induced
      secretory responses. 3 To establish the functional roles for Y(1) and Y(2)
      receptors, +/+ tissues were pretreated with either the Y(1) or Y(2) receptor
      antagonist (BIBO3304 (300 nM) or BIIE0246 (1 microM), respectively) and
      veratridine responses were compared with those from Y(1)-/- or Y(2)-/- colon.
      Neither BIBO3304 nor Y(1)-/- altered veratridine-induced secretion, but Y(1)
      agonist responses were abolished in both preparations. In contrast, the Y(2)
      antagonist BIIE0246 significantly amplified veratridine responses in +/+ mucosa.
      Unexpectedly, NPY-/- colon exhibited significantly attenuated veratridine
      responses (between 1 and 5 min). 4 We demonstrate that electrogenic veratridine
      responses in mouse colon are noncholinergic and that NPY can act directly upon
      epithelia, a Y(1) receptor effect. The enhanced veratridine response observed in
      +/+ tissue following BIIE0246, indicates that Y(2) receptors are located on
      submucosal neurons and that their activation by NPY will inhibit enteric
      noncholinergic secretory neurotransmission. 5 We also demonstrate Y(1) and Y(2)
      receptor-mediated antisecretory tone in +/+ colon and show selective loss of each
      in Y(1) and Y(2) null colon respectively. In NPY-/- tissue, only Y(1)-mediated
      tone was present, this presumably being mediated by endogenous endocrine peptide
      YY. Y(2) tone was absent from NPY-/- (and Y(2)-/-) colon and we conclude that NPY
      activation of neuronal Y(2) receptors attenuates secretory neurotransmission
      thereby providing an absorptive electrolyte tone in isolated colon.

PMID- 16100527
TI  - Inhibition of endogenous hydrogen sulfide formation reduces the organ injury
      caused by endotoxemia.
AB  - Hydrogen sulfide (H2S) is a naturally occurring gaseous transmitter, which may
      play important roles in normal physiology and disease. Here, we investigated the
      role of H2S in the organ injury caused by severe endotoxemia in the rat. Male
      Wistar rats were subjected to acute endotoxemia (Escherichia coli
      lipopolysaccharide (LPS) 6 mg kg(-1) intravenously (i.v.) for 6 h) and treated
      with vehicle (saline, 1 ml kg(-1) i.v.) or DL-propargylglycine (PAG, 10-100 mg
      kg(-1) i.v.), an inhibitor of the H2S-synthesizing enzyme cystathionine-gamma
      lyase (CSE). PAG was administered either 30 min prior to or 60 min after the
      induction of endotoxemia. Endotoxemia resulted in circulatory failure
      (hypotension and tachycardia) and an increase in serum levels of alanine
      aminotransferase and aspartate aminotransferase (markers for hepatic injury),
      lipase (indicator of pancreatic injury) and creatine kinase (indicator of
      neuromuscular injury). In the liver, endotoxemia induced a significant increase
      in the myeloperoxidase (MPO) activity, and in the expression and activity of the
      H2S-synthesizing enzymes CSE and cystathionine-beta-synthase. Administration of
      PAG either prior to or after the injection of LPS dose-dependently reduced the
      hepatocellular, pancreatic and neuromuscular injury caused by endotoxemia, but
      not the circulatory failure. Pretreatment of rats with PAG abolished the LPS
      induced increase in the MPO activity and in the formation of H2S and in the
      liver. These findings support the view that an enhanced formation of H2S
      contributes to the pathophysiology of the organ injury in endotoxemia. We propose
      that inhibition of H2S synthesis may be a useful therapeutic strategy against the
      organ injury associated with sepsis and shock.

PMID- 16100528
TI  - Functional characterisation of the S512Y mutant vanilloid human TRPV1 receptor.
AB  - 1 Mammalian transient receptor potential (TRP) channels include the nonselective
      cation channel TRPV1, which is activated by a range of stimuli including low pH,
      vanilloids and heat. Previously, selective mutagenesis experiments identified an
      intracellular residue (S512Y) critical to discriminating between pH and vanilloid
      (capsaicin) gating of the rat TRPV1 receptor. 2 In this study, switching the
      equivalent residue in the human TRPV1 (which has some significant differences
      with the rat TRPV1) also rendered this channel relatively insensitive to
      activation by capsaicin and proved critical in determining the receptor's
      sensitivity to the putative endovanilloid N-arachidonoyl-dopamine (NADA),
      suggesting a similar mode of activation for these two agonists. 3 Potency of pH
      gating was reduced; however, voltage-dependent outward rectification properties
      of the pH-dependent current and gating by heat and pH sensitisation of the S512Y
      heat response remained unaffected. 4 Surprisingly, residual capsaicin gating was
      detected and could be sensitised by pH even in the presence of a competitive
      antagonist. Taken together, these findings indicate that effective functional
      interaction of capsaicin with the S512Y channel still occurred, although the
      vanilloid-dependent gating per se was severely compromised. 5 This observation
      provides additional evidence for capsaicin interacting at multiple sites,
      distinct from the S512 residue located close to the intracellular face of the
      pore.

PMID- 16100530
TI  - [Writing yourself or copying--is it really new?].

PMID- 16100529
TI  - Inhibitors of fatty acid amide hydrolase reduce carrageenan-induced hind paw
      inflammation in pentobarbital-treated mice: comparison with indomethacin and
      possible involvement of cannabinoid receptors.
AB  - The in vivo effect of inhibitors of fatty acid amide hydrolase (FAAH) upon oedema
      volume and FAAH activity was evaluated in the carrageenan induced hind paw
      inflammation model in the mouse. Oedema was measured at two time points, 2 and 4
      h, after intraplantar injection of carrageenan to anaesthetised mice.
      Intraperitoneal (i.p.) injections of the FAAH inhibitor URB597 (0.1, 0.3, 1 and 3
      mg kg(-1)) 30 min prior to carrageenan administration, dose-dependently reduced
      oedema formation. At the 4 h time point, the ED(50) for URB597 was approximately
      0.3 mg kg(-1). Indomethacin (5 mg kg(-1) i.p.) completely prevented the oedema
      response to carrageenan. The antioedema effects of indomethacin and URB597 were
      blocked by 3 mg kg(-1) i.p. of the CB(2) receptor antagonist SR144528. The effect
      of URB597 was not affected by pretreatment with the peroxisome proliferator
      activated receptor gamma antagonist bisphenol A diglycidyl ether (30 mg kg(-1)
      i.p.) or the TRPV1 antagonist capsazepine (10 mg kg(-1) i.p.), when oedema was
      assessed 4 h after carrageenan administration. The CB(1) receptor antagonists
      AM251 (3 mg kg(-1) i.p.) and rimonabant (0.5 mg kg(-1) i.p.) gave inconsistent
      effects upon the antioedema effect of URB597. FAAH measurements were conducted ex
      vivo in the paws, spinal cords and brains of the mice. The activities of FAAH in
      the paws and spinal cords of the inflamed vehicle-treated mice were significantly
      lower than the corresponding activities in the noninflamed mice. PMSF treatment
      almost completely inhibited the FAAH activity in all three tissues, as did the
      highest dose of URB597 (3 mg kg(-1)) in spinal cord samples, whereas no obvious
      changes were seen ex vivo for the other treatments. In conclusion, the results
      show that in mice, treatment with indomethacin and URB597 produce SR144528
      sensitive anti-inflammatory effects in the carrageenan model of acute
      inflammation.

PMID- 16100531
TI  - [The patient in centrum].

PMID- 16100532
TI  - [Comprehensive cardiovascular surgery].

PMID- 16100533
TI  - [Reflux surgery].

PMID- 16100534
TI  - [Anti-reflux surgery in Norway].
AB  - BACKGROUND: The aim of this study was to investigate the incidence of gastro
      oesophageal antireflux surgery in Norway from 1999 to 2003, in comparison with
      the 1990 to 1998 period. MATERIAL AND METHODS: Operation codes for laparoscopic
      and open antireflux surgery were compiled from the Norwegian Patient Registry for
      analysis of incidence rates, geographic variations, postoperative hospital stay
      and rates of readmission. RESULTS: The incidence rates of antireflux operation in
      1999-2003 were 18.6 per 100,000 men and 10.2 per 100,000 women, a ten-fold
      increase compared to 1990. There were significant differences in operation rates
      between the five Norwegian health regions, highest in northern region. In 1999,
      85% of the patients had a laparoscopic operation, compared with 89% in 2003.
      Postoperative hospital stay was significantly shorter after laparoscopic
      operations. The proportion of laparoscopic procedures varied between the regions
      (78%-93%). The total rate of readmission within 60 days was 7%. There was no
      significant difference between readmission rates for patients treated by
      laparoscopy (6%) compared to patients treated by laparotomy (9%). In one health
      region, a high proportion of the patients were day surgery cases. CONCLUSION: The
      incidence of antireflux operation increased strongly during the 1990s and varies
      significantly between the Norwegian health regions. Laparoscopy is the leading
      mode of surgery. Patients treated by open surgery have a significant longer
      postoperative hospital stay than patients treated by laparoscopy.

PMID- 16100535
TI  - [Patients' expectations of antibiotics for acute respiratory tract infections].
AB  - BACKGROUND: We wanted to examine patients' expectations for antibiotics when
      presenting with symptoms of ARTI, and also to see whether there were any
      differences in this respect between Norwegians and immigrants. In addition we
      wanted to find out whether doctors perceived these expectations and whether it
      influenced their prescribing. MATERIAL AND METHODS: Questionnaire survey at the
      Oslo emergency service; 180 patients with symptoms of ARTI and 27 doctors
      participated. The patients were divided into a Nordic and a non-Nordic group.
      RESULTS: Among the patients, 38% expected antibiotics. There were no significant
      differences between the Nordic and the non-Nordic group. Patients who reported
      they were very/quite ill wanted antibiotics more often than those who reported
      they were quite well. Age above 30 was also associated with expectation of
      antibiotics. The doctors perceived the expectations of 41% of the patients who
      wanted antibiotics and of 69% of those who didn't. When the doctor thought
      patients wanted antibiotics, 56% of them got a prescription. INTERPRETATION: Less
      than half of the patients with symptoms of ARTI wanted antibiotics. There were no
      differences between Norwegians and immigrants. The doctors were better at
      perceiving negative expectations for antibiotics. We have reason to believe that
      doctors' perceptions of patient expectations influence their prescribing.

PMID- 16100536
TI  - [Ultrasound screening for hip dysplasia in newborns and treatment with Frejka
      pillow].
AB  - BACKGROUND: The prevailing strategy concerning ultrasound screening for DDH in
      newborns in Norway does not intercept all who should be treated. In recent years
      typical rates for hospital treatment of late hip dislocations in newborn have
      been 15-20 cases. By universal ultrasound examination, 10-20 % of the newborns
      present with "physiological immature" hips. By this we mean hips with subnormal
      ultrasound values that will normalise in the course of the neonatal period. An
      agreed basis of defined and standardised criteria in order to diagnose and treat
      physiological immature hips is required. We hope tat this study will contribute
      to the final solution to these questions. MATERIAL AND METHODS: Over the period 1
      February 1998 through 2002 we had 2466 alive newborns at our hospital. 26 were
      directly transferred to another hospital, 130 were left out because of limited
      skills or inadequate training in ultrasound among temporary staff. The hips have
      been graduated morphologically in accordance with Graf's alpha angle. All
      newborns have been investigated by ultrasound and clinical examination with
      Ortolani/Barlow test 1-3 day after birth. Those with diagnosed dysplasia (alpha <
      50 masculine) and those with positive clinic and physiological immature hip were
      immediately treated with Frejka pillow. Those with negative clinic and
      physiological immature hip were revaluated after 4 weeks by ultrasound, and those
      still immature were given Frejka pillow. Duration of pillow treatment was 4
      months, followed by further clinically and radiological surveillance. All infants
      given the pillow treatment were clinically examined 2-3 months after they were
      able to walk without support, and again 1-5 years later radiologically. RESULTS:
      Of the newborn, 31 (1.3%) had a positive Ortolani/Barlow test. Among them, 7 had
      dysplasia, 20 immature hip; 4 were normal. Among the 2275 infants with normal
      clinic, 9 had dysplasia and 232 (10.9%) had at least one physiological immature
      hip. After 4 weeks, 26 still had immature hip by ultrasound evaluation. A total
      of 62 infants (2.7%) were treated with Frejka pillow. At the "walk alone" control
      and the radiological control 1-5 years later, there were no pathological
      findings, specially no sign of aseptic necrosis. In the total material we had 2
      girls with late subluxations, detected at the age of 8 and 10 months. Both had
      normal clinic with an ultrasound immature hip at birth. They should have been
      followed up, but were missed, for uncertain reasons. Both attained normal hips
      after treatment. CONCLUSION: Our study of universal ultrasound screening for DDH
      of the hips in newborns shows that 1 % of the infants born with normal hips
      clinically still have physiological immature hips at the age of 4 weeks. Taking
      those into account as potentially dysplastic, it gives an overall treatment rate
      of 2.7%. Today, the only possible way to intercept those physiological immature
      hips that will not normalise is by universal ultrasound examination. For these
      children, early treatment with Frejka pillow is effective, without any risk of
      iatrogenic injury.

PMID- 16100537
TI  - [Infantile spasms].
AB  - BACKGROUND: Infantile spasms are an epileptic manifestation typical of infancy.
      The spasms may be associated with a wide spectrum of brain abnormalities and
      diseases, but coexisting pathology is not always found. Prognosis depends to a
      substantial extent on the underlying condition. Most of the traditional
      antiepileptics are not effective. Adrenocorticotropic hormone (ACTH) and more
      recently vigabatrin are the most common first-line medications. MATERIAL AND
      METHODS: We have performed a literature search mainly in the PubMed database on
      the treatment of infantile spasms. The results are discussed in relation to
      Norwegian practice, for which the Norwegian Paediatric Society's recommendations
      are the main guidelines. RESULTS/INTERPRETATION: Vigabatrin has emerged as an
      accepted first-line medication for infantile spasms in Norway and many other
      countries, although it has not been shown that this therapy in general is as
      effective as ACTH/steroids. Well-designed treatment studies have been difficult
      to carry out. Until the final results of such ongoing studies should give
      different signals, it seems reasonable to continue to give vigabatrin before
      hormones. Oral steroids can probably be tried before ACTH, although a firm
      conclusion about this has yet to be drawn.

PMID- 16100538
TI  - [Episodic ataxias].
AB  - BACKGROUND: Episodic ataxias (EAs) exist in sporadic and familial forms. They
      have considerable genetic and clinical heterogeneity. Better understanding of the
      disorders will hopefully improve management. MATERIAL AND METHODS: This review is
      based on personal experience and recent literature. RESULTS: EAs are rare
      autosomal dominant paroxysmic disorders. At present, five forms have been
      identified. EA 1 is caused by mutations in the potassium channel gene KCNA1 on
      chromosome 12p13, EA 2 by mutations in the calcium channel gene CACNA1A gene on
      chromosome 19p13, and EA 5 by mutations in the calcium channel gene CACNB4&beta
      on chromosome 2q22-q23. Neither gene nor linkage has been identified for EA 3 and
      4. As the name indicates, EAs are characterized by paroxystic ataxia. Patients
      with EA 1 also have interictal myokymia. EAs are characterized by both locus and
      allelic heterogeneity, since different genes can cause an almost similar
      phenotype and different mutations in a gene can cause different disorders. Beside
      EA, mutations in the KCNA1 gene can cause partial epilepsy and myokymia alone,
      mutations in the CACNA1A gene can cause familial hemiplegic migraine 1 and
      spinocerebellar ataxia 6, while mutations in the CACNB4&beta4 gene can cause
      generalized epilepsy and juvenile myoclonic epilepsy. EA can often be efficiently
      treated with acetazolamide. INTERPRETATION: EAs are rare autosomal dominant
      disorders caused by mutations in ion-channel genes. The disorders are not life
      threatening but disabling without treatment or when medical treatment is
      ineffective or not tolerated.

PMID- 16100539
TI  - [Cerebral cavernous malformations].
AB  - BACKGROUND: Cerebral cavernous malformations exist in sporadic and familial
      forms. They have considerable genetic and clinical heterogeneity. Better
      understanding of these disorders may improve management. MATERIAL AND METHODS:
      This review is based on personal experience and recent literature. RESULTS:
      Cerebral cavernous malformations are venous malformations that can be detected
      with gradient echo MRI of the brain. Approximately 0.5% of the general population
      have the sporadic form with a single or a few cerebral cavernous malformations
      which mostly are asymptomatic. Those with the familial form usually have several
      cavernous malformations caused by an autosomal dominant condition. So far, 3 loci
      have been identified: CCM1 on chromosome 7q, CCM2 on chromosome 7p, and CCM3 on
      chromosome 3q, occurring in, respectively, approximately 40%, 20% and 40% of the
      families. CCM1 is caused by a mutation in the KRIT1 gene and CCM2 is caused by a
      mutation in the MGC4607 gene, while the gene for CCM3 is not yet identified. Mean
      age at onset is 20-40, but onset can occur at all ages. The most frequent
      symptoms are seizures, cerebral haemorrhage, chronic headache and focal
      neurological deficits. Many carriers are, however, asymptomatic. INTERPRETATION:
      Sporadic cerebral cavernous malformation is often asymptomatic, while the
      familial form shows phenotypic and genetic heterogeneity. The symptoms are
      depending on the location of the malformations as well as whether haemorrhage
      does occur.

PMID- 16100540
TI  - [Endoscopic stenting of malignant colorectal strictures].
AB  - BACKGROUND: Stenting of malignant colorectal strictures has been used in the
      management of colorectal obstruction in order to convert acute into elective
      surgery ("bridge to surgery") as well as to avoid surgery in disseminated
      disease. MATERIAL AND METHOD: There are increasing numbers of international
      publications available. We have identified English-language reports from Pubmed.
      In addition we present our results with our first fifteen patients. RESULTS: The
      results reported in the international literature are encouraging and similar.
      Technical success rates were achieved in about 90%, stent migration and re
      obstruction in about 10%. The results from our hospital were consistent with
      those in the international literature. CONCLUSION: Stenting of malignant
      colorectal strictures is an effective and safe definitive procedure in the
      palliation of malignant colorectal obstruction. Acute colorectal surgery may be
      converted into elective.

PMID- 16100541
TI  - [Gait analysis--a new diagnostic tool].
AB  - Three-dimensional gait analysis is a systematic measurement, description, and
      assessment of human gait. Gait analysis is established as a useful diagnostic
      tool in patients with gait problems, as it is not possible to obtain an adequate
      and detailed understanding of such a complex mechanism as gait in a conventional
      clinical examination. The method has provided a better understanding of both
      normal gait and abnormal gait patterns; it is a suitable instrument for
      evaluation of treatment results as well as for scientific work. The first gait
      laboratory for clinical use in Norway was established in 2002 in the Section for
      child neurology at Rikshospitalet University Hospital in Oslo, Norway. In this
      article the procedure for gait analysis is described and the clinical value is
      indicated by a case record of a child with cerebral palsy. Gait analysis has
      entailed a change of policy with regard to surgical treatment in this patient
      group. Previously, operative intervention at a single level was usual, whereas
      current practice involves simultaneous interventions at several levels of both
      lower extremities. After three years' experience we recommend gait analysis in
      routine diagnostics, particularly as a preoperative evaluation, in all children
      with gait problems and in the follow up after surgery or other treatment.

PMID- 16100542
TI  - [Treatment of combined carotid and cardiac disease].
AB  - BACKGROUND: The proper management strategy for patients with combined carotid and
      cardiac disease remains unsettled. It is controversial whether the operations
      should be synchronous, staged or reversed staged, and most publications also lack
      conservatively treated control groups. The role of endovascular treatment in this
      situation has not been documented. We present our current treatment strategy and
      results. MATERIAL AND METHODS: During the period January 2001 to December 2003,
      95 procedures for internal carotid artery stenosis were performed in 81 patients.
      Median age was 70 years, range 44-83; 24 were women. In 37 patients invasive
      treatment of carotid stenosis and cardiac disease was performed (group A). In
      another 23 patients the carotid stenoses were treated invasively, while the
      cardiac disease was treated conservatively (group B). No heart disease was
      diagnosed in 21 patients treated for carotid stenoses (group C). Postoperative
      stroke/death was registered after all interventions. RESULTS: Stroke/death: Group
      A: one ipsilateral non-disabling stroke after carotid endarterectomy and one
      cardiac death after coronary artery bypass surgery (5.4%). Group B: one
      ipsilateral fatal cerebral haemorrhage and 1 contralateral ischaemic stroke
      (8.7%). Group C: none. DISCUSSION: Meta-analyses have calculated the risk of
      stroke/death after treatment for combined carotid and cardiac disease to be 7-9%,
      independently of whether the procedures are performed synchronously, staged or
      reversed staged. Our results are comparable. The aim of treatment for carotid and
      cardiac disease is to prevent death, stroke and heart failure. The benefit from
      treatment thus depends on a low complication rate, but patients with combined
      disease have an increased risk of complications. Counseling of these patients
      should be based on a multidisciplinary approach, taking into account all possible
      treatment options including conservative, endovascular and surgical, with an aim
      to reducing total cardiovascular risk.

PMID- 16100543
TI  - [Methadone-induced heart arrhythmia].
AB  - There is an ongoing debate over whether it is necessary to screen patients with
      an ECG before and during therapy with methadone. We present two patients who
      developed QT prolongation and sustained ventricular arrhythmias during treatment.
      Our experience as well as a literature survey indicate that an ECG should be
      performed before and during long-term methadone treatment.

PMID- 16100544
TI  - [Pelvimetry with compute tomography].
AB  - BACKGROUND: In 1993, Ullevaal University Hospital started CT pelvimetry. The
      accuracy of CT pelvimetric measurements and a low fetal dose are very important.
      In our study we tested the accuracy of CT pelvimetry and measured the fetal dose
      and the effective dose to the mother. METHOD: A lead scalar was exposed in
      different heights compared to the isocentre. Measurements were done at front and
      side scout views and compared to the real scale. Dose estimates were done in CT
      dosimetry (NRPB). Effective doses to patient as well as fetal doses were measured
      in this study. Fetal dose was estimated as uterus dose. RESULTS: Our results show
      that the measurements are overestimates when the table is moved away from the
      isocentre against the tube. If the table is moved away from the tube and against
      the detector, the measurements are underestimates. The measurements in the
      isocentre are accurate. This means that CT pelvimetric measurements are accurate
      if the patient is placed in the isocentre. In our study the estimated fetal dose
      was 0.74 mGy and mother's effective dose was 0.3 mSv. INTERPRETATION: Our results
      show that the fetal dose is as low or lower than with conventional pelvimetry.
      The CT pelvimetric measurements are accurate if they are performed on patients in
      the isocentre. We recommend that CT pelvimetry replace conventional pelvimetry.

PMID- 16100545
TI  - [Skeletal tuberculosis--diagnostic challenges].
AB  - BACKGROUND: Skeletal tuberculosis is rare in Norway. The diagnosis could be
      difficult. MATERIAL: A Somalian mother and three daughters and a Somalian girl in
      the neighborhood developed skeletal tuberculosis 4-12 months after arrival in
      Norway. RESULTS AND INTERPRETATION: All had pain as their main complaint.
      Skeletal scintigraphy and MRI were decisive for demonstration of the infectious
      locus. Three patients had spondylitis, two of them with serious abscesses. Other
      localisations were the frontal bone, the humerus shaft, the femoral shaft, and
      the calcaneus. Despite no signs or symptoms of lung tuberculosis, culture of
      expectorate or bronchial lavage fluid yielded growth of Mycobacterium
      tuberculosis in four patients. This demonstrates the importance of bronchial
      material also in extrapulmonary tuberculosis.

PMID- 16100546
TI  - [Treatment of overactive bladder].

PMID- 16100547
TI  - [Population's satisfaction with hospitals before and after a hospital reform in
      Norway].
AB  - BACKGROUND: We investigated patients' satisfaction with availability and quality
      of hospital services in 2000 and 2003, that is before and after the Norwegian
      hospital reform. MATERIAL AND METHODS: The data were collected from two national
      surveys in 2000 and 2003. The participants were asked about their satisfaction
      with availability (choice and waiting time for an appointment) and quality
      (result of treatment, professional skills, service-mindedness, punctuality,
      information and available time). For each question, changes in mean satisfaction
      from 2000 to 2003, corrected for changes in the composition of the sample, were
      estimated. RESULTS: A clear and statistically significant improvement in patient
      satisfaction with the availability and quality of hospital services took place
      from 2000 to 2003. In general, patients were more satisfied with the quality than
      with the availability of hospital services. INTERPRETATION: The hospital reform
      may have contributed to improved satisfaction with hospitals, though other
      factors may also have played a part.

PMID- 16100549
TI  - [Oral cancer screening?].

PMID- 16100551
TI  - [Drug companies and continuing education].

PMID- 16100552
TI  - [Analysis of prothrombin time in primary health care].

PMID- 16100553
TI  - [A step back or training pain?].

PMID- 16100554
TI  - [Is not primum non nocere valid anymore?].

PMID- 16100556
TI  - [Wrong about the right to refuse treatment].

PMID- 16100557
TI  - [Swedish circus].

PMID- 16100558
TI  - [Independence of the Knowledge Center when it comes to drug information].

PMID- 16100559
TI  - [Drug industry, the Medical Society and the others].

PMID- 16100560
TI  - [Shorter internship?].

PMID- 16100562
TI  - Role of vascular endothelial growth factor in ovarian physiology - an overview.
AB  - In the female reproductive system, as in a few adult tissues, angiogenesis occurs
      as a normal process and is essential for normal tissue growth and development. In
      the ovary, new blood vessel formation facilitates oxygen, nutrients, and hormone
      substrate delivery, and also secures transfer of different hormones to targeted
      cells. Ovarian follicle and the corpus luteum (CL) have been shown to produce
      several angiogenic factors, however, vascular endothelial growth factor (VEGF) is
      thought to play a paramount role in the regulation of normal and abnormal
      angiogenesis in the ovary. Expression of VEGF in ovarian follicles depends on
      follicular size. Inhibition of VEGF expression results in decreased follicle
      angiogenesis and the lack of the development of mature antral follicles. The
      permeabilizing activity of VEGF is thought to be involved in follicle antrum
      formation and in the ovulatory process. In the CL, VEGF expression corresponds to
      different patterns of angiogenesis during its lifespan. In most the species,
      higher VEGF expression in the early luteal phase is essential for the development
      of a high-density capillary network in the CL. However, high VEGF expression may
      be still maintained in the mid-luteal phase to increase vascular permeability
      that results in enhancement of luteal function. During gestation, VEGF is thought
      to be important for the persistence of the CL function for a longer than in the
      nonfertile cycle period of time. Further elucidation of specific roles of VEGF in
      ovarian physiology may help to understand the phenomenon of luteal insufficiency
      and reveal novel strategies of ovarian angiogenesis manipulation to alleviate
      infertility or to control fertility.

PMID- 16100563
TI  - Embryo development and survival in beef cattle administered ergotamine tartrate
      to simulate fescue toxicosis.
AB  - Two experiments were performed to determine whether administration of ergotamine
      tartrate altered embryo development (Exp. 1) and uterine competency to establish
      pregnancy (Exp. 2) in beef cattle. Animals were fed daily either 0 (CON) or 40
      mug/kg body weight of ergotamine tartrate (ERGOT). Following a 30-d period on
      respective diets, animals in Exp. 1 were artificial inseminated at estrus (d = 0)
      and single embryo recoveries performed on day 7; whereas, animals in Exp. 2
      received two frozen-thawed embryos on day 7. As an indicator of ergotamine
      effects, prolactin was decreased throughout both experiments in ERGOT compared to
      CON animals (p<0.05). Furthermore, rectal temperature (RT) tended to increase
      during both experiments in ERGOT compared to CON (p= 0.06). In Exp. 1, embryo
      recovery (p=0.08) and the percentage of transferable embryos (p=0.09) tended to
      be greater for CON than for ERGOT. Percentage of embryos that developed to
      compacted morula or greater was increased for CON compared to ERGOT heifers
      (p<0.05). In Exp. 2, pregnancy rates of transferred embryos did not differ
      between treatment groups. Thus, administration of ERGOT to simulate fescue
      toxicosis altered developmental potential of embryos, but does not appear to
      affect uterine competency to establish pregnancy.

PMID- 16100564
TI  - In vitro contractile activity of porcine myometrium during luteolysis and early
      pregnancy: effect of oxytocin and progesterone.
AB  - The present study was undertaken to elucidate the role of OT in myometrial
      contractility in sows. Spontaneous and OT-stimulated contractions of the inner
      circular (CM) and outer longitudinal (LM) layers isolated from cyclic (Days 14
      16) and early pregnant (Days 14-16) sows were examined in six cyclic and six
      pregnant sows. In addition, the role of P(4) in the modulation of OT-induced
      uterine contractions was investigated. The contractile activity of the LM and CM
      layers was recorded in a tissue chamber filled with Krebs-Ringer solution.
      Myometrial contractility was expressed as area under the contractility curve
      (AUC) and frequency of contractions. Myometrial longitudinal and circular muscles
      exhibited spontaneous contractility in sows during both luteolysis and early
      pregnancy. The mean AUC was higher (p<0.05) in the LM layer compared to the CM
      layer in both cyclic and pregnant animals. In addition, pregnant sows were
      characterized by higher AUC in both LM and CM layers in comparison to cyclic
      sows. The CM layer was unresponsive to examined treatments. Oxytocin (1-3x10(-8)
      and 1-3x10(-7)M) increased the AUC and frequency of contractions of the LM layer
      in both examined animal groups, being more effective during luteolysis (p<0.001)
      than early pregnancy (p<0.01). Response of the LM layer to OT appeared to be
      clearly related to the initial spontaneous level of contractility. This response
      to OT was inhibited (p<0.05) in the presence of OT antagonist (10(-6)M).
      Moreover, in pregnant sows, OT-stimulated contractile activity of myometrium was
      inhibited (p<0.05) by P(4) (10(-5)M). In conclusion, OT receptors present in
      myometrial cells (especially in the LM layer) are involved in the regulation of
      contractile activity of porcine myometrium during luteolysis and early-pregnancy.
      In addition, progesterone appears to be involved in this regulation.

PMID- 16100565
TI  - Fetal losses and pathologic findings of clones derived from serum-starved versus
      serum-fed bovine ovarian granulosa cells.
AB  - The objective was to evaluate development of cloned embryos constructed with
      serum-starved versus fed ovarian granulosa cells. Fusion of somatic cells with
      cytoplasts (50.7 and 50.7%; SEM=5.5), development of cloned embryos to 8-16-cell
      (59.4 and 62.6%; SEM=6.4), and compact morula/blastocyst-stages (24.9 and 26.5%;
      SEM=8.5) was similar for serum-starved and fed groups. More heifers were
      confirmed pregnant with clones derived from serum-starved cells (9/13, 67.2%
      versus 11/25, 44%). However, embryonic loss between 29-50 days was greater for
      clones constructed with serum-starved (88.9%) versus fed (36.4%) cells.
      Development of clones derived from serum-fed cells through placentation and
      differentiation was not predictive of competency to term. Fetal deaths occurred
      in the majority of late term pregnancies as a result of complications from
      hydrallantois. Only one fetus derived from serum-fed ovarian granulosa cells
      developed to term (278 days). At birth and for approximately 9 consecutive months
      thereafter, routine veterinary examinations confirmed expected growth patterns.
      In summary, the use of serum fed granulosa cells for nuclear transfer was
      coincident with a high incidence of third trimester losses associated with
      hydrallantois and fetal oversize.

PMID- 16100566
TI  - Multiple forms of Pregnancy-Associated Glycoproteins released in vitro by porcine
      chorion or placentomal and interplacentomal explants of wild and domestic
      ruminants.
AB  - Characterization of the Pregnancy-Associated Glycoproteins (PAG) is important for
      studies of reproduction of various eutherian domestic, wild and endangered
      mammals. Distinct chorionic PAG genes are expressed in embryo-origin cells: pre
      placental trophoblast (TR) and in placental trophectoderm (TRD) of various
      entherians. This study demonstrates in vitro production of the PAG proteins
      during long-term cultures of various chorionic explants: porcine TR or TRD,
      cotyledonary (CT) of European bison (Eb), and CT or intercotyledonary (intCT)-TRD
      of the cattle. Chorionic proteins isolated from media were analyzed by homologous
      or heterologous Western immunoblotting with anti-PAG sera, raised against
      cellular bovine or secretory porcine antigens. Used anti-PAG sera identified
      diverse molecular forms of released PAG proteins: 43-69 kDa for EbPAG proteins,
      40-85 kDa for bovine PAG (bPAG), and 43-73 kDa for porcine PAG (pPAG).
      Immunoblotting revealed also that both CT and intCT-TRD explants secreted
      equivalent amounts of bPAG proteins. This useful system of in vitro protein
      production can provide native chorionic PAG proteins with placental unique
      carbohydrate chains. The PAG proteins are required as standard markers for
      diagnostic tests of pregnancy in domestic and wild mammals, in which seasonal
      reproductive processes are relatively difficult to control.

PMID- 16100567
TI  - Steroidogenic activity of chicken ovary during pause in egg laying.
AB  - The present study was designed (i) to assess the changes in the activity of 3beta
      hydroxysteroid dehydrogenase (3beta-HSD) and cytochrome P450 aromatase (P450arom)
      in the ovaries of hens which are subjected to a pause in egg laying by fasting,
      and (ii) relate these changes with progesterone (P(4)) and estradiol (E(2))
      production in the ovary. Hy-Line Brown laying hens (n=90) were fasted for 5 days
      with water deprivation only on day 3 and subsequently fed every second day up to
      day 13 and then ad libitum. Birds were euthanized (n=18) on day 0, 3, 6, 9 and 16
      of the experiment. The activities of 3beta-HSD and P450arom were evaluated in
      stroma with cortical follicles (<1mm) and in the wall of white non-hierarchical
      (1-8 mm) and yellow hierarchical follicles (>8 mm) by histochemical and
      immunohistochemical method, respectively. Ovarian P(4) and E(2) were measured
      radioimmunologically. Hens stopped egg laying on day 4 of the experiment and
      pause in egg laying lasted up to day 12. The hens then began to gradually resume
      egg laying and on day 16 all hens laid eggs. It was found that during the pause
      in egg laying: (i) the activity of 3beta-HSD in stroma and normal white follicles
      was slightly decreased while P450arom activity was significantly increased; (ii)
      in yellow hierarchical follicles which became atretic and regressed, activity of
      both enzymes were markedly decreased; (iii) ovarian P(4) production dramatically
      decreased, whereas ovarian E(2) production after an initial decrease
      significantly increased. In white atretic follicles the activity of 3beta-HSD and
      P450arom was very weak during the whole experiment. In conclusion, the present
      results indicate that during a pause in egg laying white follicles become
      resistant to atresia.

PMID- 16100568
TI  - Secretion patterns of luteinizing hormone in growing mithuns (Bos frontalis).
AB  - To characterize the luteinizing hormone (LH) secretion patterns in growing mithun
      (Bos frontalis), a semi-wild ruminant, six female mithuns (1 year old; BW: 145.5
      kg) were maintained in a semi-intensive system. Plasma progesterone (P(4)) level
      was measured in twice-a-week samples collected for six weeks to assess ovarian
      status. This was followed by a frequent sampling period. Blood samples collected
      at 15 min intervals for 9 h were assayed for plasma LH. Luteinizing hormone
      patterns consisted of pulses of varying amplitudes. Luteinizing hormone pulses
      occurred at an average rate of 0.54/h ( approximately 5 pulses/9 h). The rate did
      not differ among mithuns. The mean plasma LH levels was correlated with body
      weight (r=0.82; p<0.05) and pulse amplitude (r=0.87; p<0.01). Neither the LH
      amplitude nor the frequency was affected by time (p>0.05). The mean plasma P(4)
      concentration was 0.37 ng/ml. In conclusion, we demonstrated a pulsatile nature
      of LH secretion in growing mithuns. In addition, the mean plasma LH level and LH
      amplitude were positively correlated with body weight. It appears that in
      contrast to cattle, five LH pulses per nine hours recorded in mithuns were not an
      indication of approaching puberty.

PMID- 16100569
TI  - Expression of leptin receptor and suppressor of cytokine signaling-3 genes in
      adenohypophysis of normal-fed and fasted cows.
AB  - Expression of leptin receptor (LR) and suppressor of cytokine signaling (SOCS)-3
      genes was investigated in normal-fed and fasted cows. Fasting did not affect LR
      mRNA, but increased SOCS-3 mRNA in the adenohypophysis, suggesting that
      heightened responsiveness of fasted cows to leptin is not dependent upon
      alterations in LR or SOCS-3 mRNA in the adenohypophysis.

PMID- 16100570
TI  - Organ-specific roles for transcription factor NF-kappaB in reovirus-induced
      apoptosis and disease.
AB  - Reovirus induces apoptosis in cultured cells and in vivo. In cell culture models,
      apoptosis is contingent upon a mechanism involving reovirus-induced activation of
      transcription factor NF-kappaB complexes containing p50 and p65/RelA subunits. To
      explore the in vivo role of NF-kappaB in this process, we tested the capacity of
      reovirus to induce apoptosis in mice lacking a functional nfkb1/p50 gene. The
      genetic defect had no apparent effect on reovirus replication in the intestine or
      dissemination to secondary sites of infection. In comparison to what was observed
      in wild-type controls, apoptosis was significantly diminished in the CNS of p50
      null mice following reovirus infection. In sharp contrast, the loss of p50 was
      associated with massive reovirus-induced apoptosis and uncontrolled reovirus
      replication in the heart. Levels of IFN-beta mRNA were markedly increased in the
      hearts of wild-type animals but not p50-null animals infected with reovirus.
      Treatment of p50-null mice with IFN-beta substantially diminished reovirus
      replication and apoptosis, which suggests that IFN-beta induction by NF-kappaB
      protects against reovirus-induced myocarditis. These findings reveal an organ
      specific role for NF-kappaB in the regulation of reovirus-induced apoptosis,
      which modulates encephalitis and myocarditis associated with reovirus infection.

PMID- 16100571
TI  - Involvement of Foxo transcription factors in angiogenesis and postnatal
      neovascularization.
AB  - Forkhead box O (Foxo) transcription factors are emerging as critical
      transcriptional integrators among pathways regulating differentiation,
      proliferation, and survival, yet the role of the distinct Foxo family members in
      angiogenic activity of endothelial cells and postnatal vessel formation has not
      been studied. Here, we show that Foxo1 and Foxo3a are the most abundant Foxo
      isoforms in mature endothelial cells and that overexpression of constitutively
      active Foxo1 or Foxo3a, but not Foxo4, significantly inhibits endothelial cell
      migration and tube formation in vitro. Silencing of either Foxo1 or Foxo3a gene
      expression led to a profound increase in the migratory and sprout-forming
      capacity of endothelial cells. Gene expression profiling showed that Foxo1 and
      Foxo3a specifically regulate a nonredundant but overlapping set of angiogenesis-
      and vascular remodeling-related genes. Whereas angiopoietin 2 (Ang2) was
      exclusively regulated by Foxo1, eNOS, which is essential for postnatal
      neovascularization, was regulated by Foxo1 and Foxo3a. Consistent with these
      findings, constitutively active Foxo1 and Foxo3a repressed eNOS protein
      expression and bound to the eNOS promoter. In vivo, Foxo3a deficiency increased
      eNOS expression and enhanced postnatal vessel formation and maturation. Thus, our
      data suggest an important role for Foxo transcription factors in the regulation
      of vessel formation in the adult.

PMID- 16100572
TI  - Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears
      beta-amyloid in a mouse model of Alzheimer disease.
AB  - Amyloid beta-peptide (Abeta) appears to play a key pathogenic role in Alzheimer
      disease (AD). Immune therapy in mouse models of AD via Abeta immunization or
      passive administration of Abeta antibodies markedly reduces Abeta levels and
      reverses behavioral impairment. However, a human trial of Abeta immunization led
      to meningoencephalitis in some patients and was discontinued. Here we show that
      nasal vaccination with a proteosome-based adjuvant that is well tolerated in
      humans plus glatiramer acetate, an FDA-approved synthetic copolymer used to treat
      multiple sclerosis, potently decreases Abeta plaques in an AD mouse model. This
      effect did not require the presence of antibody, as it was observed in B cell
      deficient (Ig mu-null) mice. Vaccinated animals developed activated microglia
      that colocalized with Abeta fibrils, and the extent of microglial activation
      correlated strongly with the decrease in Abeta fibrils. Activation of microglia
      and clearing of Abeta occurred with the adjuvant alone, although to a lesser
      degree. Our results identify a novel approach to immune therapy for AD that
      involves clearing of Abeta through the utilization of compounds that have been
      safely tested on or are currently in use in humans.

PMID- 16100573
TI  - Negative regulation by thyroid hormone receptor requires an intact coactivator
      binding surface.
AB  - Thyroid hormone (TH) action is mediated by TH receptors (TRs), which are members
      of the nuclear hormone receptor superfamily. In vitro studies have demonstrated
      that TR activity is regulated by interactions with corepressor and coactivator
      proteins (CoRs and CoAs, respectively). TH stimulation is thought to involve
      dissociation of CoRs and recruitment of CoAs to the liganded TR. In contrast,
      negative regulation by TH is thought to occur via recruitment of CoRs to the
      liganded TR. The physiological role of CoAs bound to TRs, however, has yet to be
      defined. In this study, we used gene-targeting techniques to mutate the TR-beta
      locus within its activation function-2 (AF-2) domain (E457A). This mutation was
      chosen because it completely abolished CoA recruitment in vitro, while preserving
      normal triiodothyronine (T3) binding and CoR interactions. As expected, TH
      stimulated gene expression was reduced in homozygous E457A mice. However, these
      animals also displayed abnormal regulation of the hypothalamic-pituitary-thyroid
      axis. Serum thyroxine, T3, and thyroid-stimulating hormone (TSH) levels and
      pituitary Tshb mRNA levels were inappropriately elevated compared with those of
      WT animals, and L-T3 treatment failed to suppress serum TSH and pituitary Tshb
      mRNA levels. Therefore, the AF-2 domain of TR-beta is required for positive and,
      paradoxically, for negative regulation by TH in vivo.

PMID- 16100574
TI  - Schoenheimer effect explained--feedback regulation of cholesterol synthesis in
      mice mediated by Insig proteins.
AB  - End-product feedback inhibition of cholesterol synthesis was first demonstrated
      in living animals by Schoenheimer 72 years ago. Current studies define Insig
      proteins as essential elements of this feedback system in mouse liver. In
      cultured cells, Insig proteins are required for sterol-mediated inhibition of the
      processing of sterol regulatory element-binding proteins (SREBPs) to their
      nuclear forms. We produced mice with germline disruption of the Insig2 gene and
      Cre-mediated disruption of the Insig1 gene in liver. On a chow diet, these double
      knockout mice overaccumulated cholesterol and triglycerides in liver. Despite
      this accumulation, levels of nuclear SREBPs and mRNAs for SREBP target genes in
      lipogenic pathways were not reduced. Whereas cholesterol feeding reduced nuclear
      SREBPs and lipogenic mRNAs in wild-type mice, this feedback response was severely
      blunted in the double-knockout mice, and synthesis of cholesterol and fatty acids
      was not repressed. The amount of HMG-CoA reductase protein was elevated out of
      proportion to the mRNA in the double-knockout mice, apparently owing to the
      failure of cholesterol to accelerate degradation of the enzyme. These studies
      indicate that the essential elements of the regulatory pathway for lipid
      synthesis function in liver as they do in cultured cells.

PMID- 16100575
TI  - Isolation of plasma from whole blood using planar microfilters for lab-on-a-chip
      applications.
AB  - Researchers are actively developing devices for the microanalysis of complex
      fluids, such as blood. These devices have the potential to revolutionize
      biological analysis in a manner parallel to the computer chip by providing very
      high throughput screening of complex samples and massively parallel bioanalytical
      capabilities. A necessary step performed in clinical chemistry is the isolation
      of plasma from whole blood, and effective sample preparation techniques are
      needed for the development of miniaturized clinical diagnostic devices. This
      study demonstrates the use of passive, operating entirely on capillary action,
      transverse-flow microfilter devices for the microfluidic isolation of plasma from
      whole blood. Using these planar microfilters, blood can be controllably
      fractionated with minimal cell lysis. A characterization of the device
      performance reveals that plasma filter flux is dependent upon the wall shear rate
      of blood in the filtration channel, and this result is consistent with macroscale
      blood filtration using microporous membranes. Also, an innovative microfluidic
      layout is demonstrated that extends device operation time via capillary action
      from seconds to minutes. Efficiency of these microfilters is approximately three
      times higher than the separation efficiencies predicted for microporous membranes
      under similar conditions. As such, the application of the microscale blood
      filtration designs used in this study may have broad implications in the design
      of lab-on-a-chip devices, as well as the field of separation science.

PMID- 16100576
TI  - Mini-electrochemical detector for microchip electrophoresis.
AB  - This paper presents the development of a mini-electrochemical detector for
      microchip electrophoresis. The small size (3.6 x 5.0 cm2, W x L) of the detector
      is compatible with the dimension of the microchip. The use of universal serial
      bus (USB) ports facilitates installation and use of the detector, miniaturizes
      the detector, and makes it ideal for lab-on-a-chip applications. A fixed 10 M ohm
      feedback resistance was chosen to convert current of the working electrode to
      voltage with second gain of 1, 2, 4, 8, 16, 32, 64 and 128 for small signal
      detection instead of adopting selectable feedback resistance. Special attention
      has been paid to the power support circuitry and printed circuit board (PCB)
      design in order to obtain good performance in such a miniature size. The working
      electrode potential could be varied over a range of +/-2.5 V with a resolution of
      0.01 mV. The detection current ranges from -0.3 x 10(-7) A to 2.5 x 10(-7) A and
      the noise is lower than 1 pA. The analytical performance of the new system was
      demonstrated by the detection of epinephrine using an integrated PDMS/glass
      microchip with detection limit of 2.1 microM (S/N = 3).

PMID- 16100577
TI  - Use of self assembled magnetic beads for on-chip protein digestion.
AB  - The use of grafted trypsin magnetic beads in a microchip for performing protein
      digestion is described. The PDMS device uses strong magnets to create a magnetic
      field parallel to the flow with a strong gradient pointing through the center of
      the chip channel. This allows for the formation of a low-hydrodynamic resistance
      plug of magnetic trypsin beads that serves as a matrix for protein digestion.
      This device represents an inexpensive way of fabricating a multi open-tubular
      like column with an appropriate pore size for proteins. Kinetics studies of the
      hydrolysis of a model peptide show a 100-fold increase in digestion speed
      obtained by the microsystem when compared to a batch wise system. This system
      also offers the great advantage of easy replacement, as the bead matrix is easily
      washed out and replaced. High performance and reproducibility for digesting
      recombinant human growth hormone are confirmed by analysing the digest products
      in both CE and MALDI-TOF MS. Similar sequence coverage (of about 44%) is obtained
      from MS analysis of products after 10 minutes on-chip and 4 h with soluble
      trypsin in bulk.

PMID- 16100578
TI  - A new pulsed electric field microreactor: comparison between the laboratory and
      microtechnology scale.
AB  - This paper presents a new microreactor dedicated for pulsed electric field
      treatment (PEF), which is a pasteurization method that inactivates microorganisms
      with short electric pulses. The PEF microreactor consists of a flow-through
      channel with a constriction where the electric field is focussed. Compared to a
      laboratory-scale setup 25 times lower voltages were needed to obtain the same
      electric field strength due to the close electrode spacing. A finite element
      model showed that the electric field intensity is very homogeneous throughout the
      channel, which is crucial for the pasteurization processes. Experiments where
      artificial vesicles, loaded with carboxyfluorescein, were electroporated showed
      that the maximum transmembrane potential adequately described the processes both
      in the microreactor and the laboratory-scale setup, although the length scales
      are different. Electroporation started at a transmembrane potential of 0.5 V,
      reaching a maximum fraction of electroporated vesicles of 51% at a transmembrane
      potential of 1.5 V. The partial electroporation is not a result of the
      heterogenity of the vesicles or the electric field. With this new PEF
      microreactor it is possible to study the PEF process in more detail.

PMID- 16100579
TI  - Model and verification of electrokinetic flow and transport in a micro
      electrophoresis device.
AB  - We investigate the electrokinetic flow and transport within a micro
      electrophoresis device. A mathematical model is set up, which allows to perform
      two-dimensional, time-dependent finite-element simulations. The model reflects
      the dominant features of the system, namely electroosmosis, electrophoresis,
      externally-applied electrical potentials, and equilibrium chemistry. For the
      solution of the model equations we rely on numerical simulations of the core
      region, while the immediate wall region is treated analytically at leading order.
      This avoids extreme refinements of the numerical grid within the EDL. An
      asymptotic matching of both solutions and subsequent superposition, nevertheless,
      provides an approximation for the solution in the entire domain. The results of
      the simulations are verified against experimental observation and show good
      agreement.

PMID- 16100580
TI  - Self-referencing a single waveguide grating sensor in a micron-sized deep flow
      chamber for label-free biomolecular binding assays.
AB  - In order to allow the design of increasingly sensitive label-free biosensors,
      compensation of environmental fluctuations is emerging as the dominant hurdle.
      The system and technique presented here utilize a unique combination of
      microfluidics, optical instrumentation, and image processing to provide a
      reference signal for each label-free biomolecular binding assay. Moreover, this
      reference signal is generated from the same sensor used to detect the
      biomolecular binding events. In this manner, the reference signal and the binding
      signal share nearly all common-mode noise sources (temperature, pressure,
      vibration, etc.) and their subtraction leaves the purest binding signal possible.
      Computational fluid dynamic simulations have been used to validate the flow
      behavior and thermal characteristics of the fluids inside the sensing region.
      This system has been demonstrated in simple bulk refractive index tests, as well
      as small molecule (biotin/streptavidin) binding experiments. The ability to
      perform not only simple binding but also control experiments has been discussed,
      indicating the wide applicability of the technique.

PMID- 16100581
TI  - Numerical simulation of polymerization in interdigital multilamination
      micromixers.
AB  - Free radical polymerization in microfluidic devices modeled with the help of
      numerical simulations is discussed. The simulation method used allows the
      simultaneous solvation of partial differential equations resulting from the
      hydrodynamics, thermal and mass transfer (convection, diffusion and chemical
      reaction). Three microfluidic devices are modeled, two interdigital
      multilamination micromixers respectively with a large and short focusing section,
      and a simple T-junction followed by a microtube reactor together considered as a
      bilamination micromixer with a large focusing section. The simulations show that
      in spite of the heat released by the polymerization reaction, the thermal
      transfer in such microfluidic devices is high enough to ensure isothermal
      conditions. Moreover, for low radial Peclet number, microfluidic devices with a
      large focusing section can achieve better control over the polymerization than a
      laboratory scale reactor as the polydispersity index obtained is very close to
      the theoretical limiting value. As the characteristic dimension of the
      microfluidic device increases, i.e. for high radial Peclet number, the reactive
      medium cannot be fully homogenized by the diffusion transport before leaving the
      system resulting in a high polydispersity index and a loss in the control of the
      polymerization.

PMID- 16100582
TI  - Rapid method for design and fabrication of passive micromixers in microfluidic
      devices using a direct-printing process.
AB  - We developed a facile and rapid one-step technique for design and fabrication of
      passive micromixers in microfluidic devices using a direct-printing process. A
      laser printing mechanism was dexterously adopted to pattern the microchannels
      with different gray levels using vector graphic software. With the present
      method, periodically ordered specific bas-relief microstructures can be easily
      fabricated on transparencies by a simple printing process. The size and shape of
      the resultant microstructures are determined by the gray level of the graphic
      software and the resolution of the laser printer. Patterns of specific bas-relief
      microstructures on the floor of a channel act as obstacles in the flow path for
      advection mixing, which can be used as efficient mixing elements. The mixing
      effect of the resultant micromixer in microfluidic devices was evaluated using
      CCD fluorescence spectroscopy. We found that the mixing performance depends
      strongly on the gray level values. Under optimal conditions, fast passive mixing
      with our periodic ordered patterns in microfluidic devices has been achieved at
      the very early stages of the laminar flow. In addition, fabrication of
      micromixers using the present versatile technique requires less than an hour. The
      present method is promising for fabrication of micromixers in microfluidic
      devices at low cost and without complicated devices and environment, providing a
      simple solution to mixing problems in the micro-total-analysis-systems field.

PMID- 16100583
TI  - The micro patterning of glutaraldehyde (GA)-crosslinked gelatin and its
      application to cell-culture.
AB  - This paper proposes a novel technique for fabricating micro patterns of
      glutaraldehyde (GA)-crosslinked gelatin. It provides another means to crosslink
      gelatin other than using photo-sensitizing agents, and the micro patterns of GA
      crosslinked gelatin can still be made successfully by accessing conventional
      photolithography. A much less toxic and increased biocompatible approach to
      strengthening the gelatin microstructures can be developed according to this
      idea. This paper also describes a potential methodology for using GA-crosslinked
      gelatin patterns as single-cell culture bases. The best spatial resolution of the
      micro gelatin bases can reach 10 microm, and the selective growing density of
      human Mesenchymal stem cells on the gelatin patterns surpasses the density on the
      glass substrate by 2-3 orders of magnitude.

PMID- 16100584
TI  - Effects of nanoconfinement on the morphology and reactivity of organic materials.
AB  - When organic materials are placed in environments which physically confine the
      materials at the nanometre scale, interfacial effects and confinement-induced
      loss of entropy can significantly alter materials' properties such as the glass
      transition temperature as well as the nanoscale morphology as compared to a
      "free" system. In block copolymers, nanoconfinement leads to a range of unusual
      self-organized nanoscale morphologies. In this article, attempts to induce
      nanoconfinement effects in new polymer systems as well as at interfaces will be
      highlighted and some possible future implications for organic synthesis and
      biology will be discussed.

PMID- 16100585
TI  - Organogel of an 8-quinolinol platinum(II) chelate derivative and its efficient
      phosphorescence emission effected by inhibition of dioxygen quenching.
AB  - A newly synthesized 8-quinolinol platinum(II) chelate derivative gelates various
      organic solvents, and the gel formed shows unique thermo- and solvatochromism of
      visible and phosphorescent colour in response to a sol-gel phase transition and
      possesses an attractive ability to inhibit dioxygen quenching of excited triplet
      states.

PMID- 16100586
TI  - Layer-by-layer assembly of charged poly(phenylacetylene)s with induced
      macromolecular helicity.
AB  - The macromolecular helicity of charged poly(phenylacetylene)s induced by small
      chiral guests in water can be retained by the alternative deposition of achiral
      polyelectrolytes with opposite charges, resulting in optically active multilayer
      thin films with a macromolecular helicity memory.

PMID- 16100587
TI  - Novel HEXOL-type cyclometallated iridium(III) complexes: stereoselective
      synthesis and structure elucidation.
AB  - Two diastereoisomers of tetranuclear cyclometallated iridium complexes, either
      having an inner core of HEXOL-type [Ir(IrCl2)3]6+ unit and a surface of six
      chiral, didentate, cyclometallated ligands, are stereoselectively synthesized
      from an enantiopure pinenopyridine derivative.

PMID- 16100588
TI  - Allosteric pitch length tuning of a dinuclear double helicate.
AB  - Self assembly of the ditopic ligand L1 with Cu2+ gives the dinuclear double
      helicate [Cu2(L1)2]4+, which can further coordinate s-block cations. This
      coordination alters the helicate pitch to a variety of different lengths
      depending on the size and charge of the guest cation.

PMID- 16100589
TI  - Simple iron-amine catalysts for the cross-coupling of aryl Grignards with alkyl
      halides bearing beta-hydrogens.
AB  - Mixtures of iron(III) chloride and appropriate amine ligands are active catalysts
      for the coupling of aryl Grignard reagents with primary and secondary alkyl
      halide substrates bearing beta-hydrogens, under mild and simple reaction
      conditions.

PMID- 16100590
TI  - Lower rim mono-functionalization of resorcinarenes.
AB  - A versatile, scaleable, one step synthesis of a lower rim mono-functionalized
      resorcinarene is described.

PMID- 16100591
TI  - A high throughput screening method for the selection of zeolites for binding
      cations.
AB  - An effective high throughput screening technique is described for the rapid
      analysis of zeolites as binding agents for cationic sequestration.

PMID- 16100592
TI  - Photochemical release of nitric oxide from a regenerable, sol-gel encapsulated Ru
      salen-nitrosyl complex.
AB  - Light activation leads to release of NO from a silicate sol-gel material SG-RuNO
      prepared from the ruthenium complex, [Ru(salen)(OH2)(NO)]+ (salen = N,N'-bis
      (salicylidene)ethyl-enediaminato); after photochemical NO photolabilization, SG
      RuNO can be regenerated from the spent material via the subsequent reaction with
      aqueous nitrite.

PMID- 16100593
TI  - Preparation of biohybrid amphiphiles via the copper catalysed Huisgen [3 + 2]
      dipolar cycloaddition reaction.
AB  - Biohybrid amphiphiles have been prepared from terminal azide functionalised
      polystyrene and an alkyne functionalised peptide or protein via a Cu(I) catalysed
      Huisgen [3 + 2] dipolar cycloaddition reaction.

PMID- 16100594
TI  - 2-Phenallyl as a versatile protecting group for the asymmetric one-pot three
      component synthesis of propargylamines.
AB  - 2-Phenallyl was found to be a versatile protecting group of primary amines for
      the asymmetric one-pot three-component synthesis of propargylamines which leads
      to enantiomeric excess of up to 96%; it can be easily removed with a palladium(0)
      catalyzed allylic substitution using 1,3-dimethylbarbituric acid as a
      nucleophile.

PMID- 16100595
TI  - New synthesis method for nickel phosphide hydrotreating catalysts.
AB  - Nickel phosphide particles on silica and alumina support were prepared from metal
      or metal oxide particles by treatment with phosphine and hydrogen at moderate
      temperature, resulting in small particle sizes equivalent to that of the
      precursor particle size.

PMID- 16100596
TI  - Shape controlled growth of gold nanoparticles by a solution synthesis.
AB  - The shape of gold nanoparticles has been successfully tuned among penta-twinned
      decahedrons, truncated tetrahedrons, cubes, octahedrons, hexagonal thin plates by
      introducing a small amount of salt into a N,N-dimethylformamide (DMF) solution
      containing poly(vinyl pyrrolidone) (PVP), and changing the temperature or the
      concentration of the gold precursor.

PMID- 16100597
TI  - Highly luminescent water-soluble CdTe nanowires as fluorescent probe to detect
      copper(II).
AB  - Highly luminescent water-soluble CdTe nanowires synthesized in one step were used
      to detect copper(II) selectively below 0.078 microM in the presence of other
      physiologically relevant cations.

PMID- 16100598
TI  - A new simple synthesis of poly(thiophene-methine)s.
AB  - Acid-promoted polycondensation of 3,4-(ethylenedioxy)thiophene-2-carbaldehyde
      leads to a conjugated heavily p-doped poly(thiophene-methine), which can be
      dedoped leading to a low band-gap neutral polymer.

PMID- 16100599
TI  - The first ternary tin(II) nitride: NaSnN.
AB  - NaSnN with the non-centrosymmetric layered structure type of KSnAs and featuring
      the new layered Zintl ion [SnN]- is the first example of a ternary nitride
      containing Sn-N bonds, and the first example of a nitride containing formally
      divalent tin.

PMID- 16100600
TI  - Immobilization of ionic liquid with polyelectrolyte as carrier.
AB  - An all-purpose approach to immobilize ionic liquids onto solid supports is
      proposed by chemical grafting on a polyelectrolyte carrier.

PMID- 16100601
TI  - Palladium(0) alkyne complexes as active species: a DFT investigation.
AB  - Alkynes have been found to be excellent ligands for Pd(0); the stability of a
      range of alkyne-Pd(0) complexes, and their reactivity in oxidative addition, have
      been investigated by DFT methods.

PMID- 16100602
TI  - Entropy-controlled supramolecular photochirogenesis: enantiodifferentiating Z-E
      photoisomerization of cyclooctene included and sensitized by permethylated 6-O
      benzoyl-beta-cyclodextrin.
AB  - In contrast to the photosensitization with a non-methylated analogue,
      supramolecular photochirogenesis with a novel permethylated mono(6-O-benzoyl)
      beta-cyclodextrin exhibited a critical dependence of the product's enantiomeric
      excess upon temperature, and possessed a large differential entropy of activation
      (-11 J K(-1) mol(-1)) for which the flexible host skeleton is likely to be
      responsible.

PMID- 16100603
TI  - A facile route to fabrication of inorganic-small organic molecule cable-like
      nanocomposite arrays.
AB  - A novel and facile method is reported for the preparation of silver iodide-small
      organic molecule (SOM) cable-like nanocomposites arrays, which involved first the
      fabrication of SOM nanotubes inside an anodic aluminium oxide (AAO) membrane, and
      then using the SOM nanotubes in AAO as secondary template to prepare the AgI
      nanowires in aqueous solution at room temperature.

PMID- 16100604
TI  - Porous polystyrene microspheres having dimpled surface structures prepared within
      micellar assemblies of amphiphilic silica particles in water.
AB  - Production of porous polystyrene microspheres having dimpled surface structures
      was demonstrated using amphiphilic and hydrophobic silica particles as structure
      directing agents.

PMID- 16100605
TI  - Thio[2-(benzoylamino)ethylamino]-beta-CD fragment modified gold nanoparticles as
      recycling extractors for [60]fullerene.
AB  - Gold particles are modified with surface-attached bis(beta-cyclodextrin)s bearing
      S-S bridges to give water-soluble cyclodextrin-modified gold nanoparticles, which
      are successfully used as recycling extractors for [60]fullerene.

PMID- 16100606
TI  - Analysis of key steps in the catalytic cross-coupling of alkyl electrophiles
      under Negishi-like conditions.
AB  - The use of tpy'(tpy'= 4,4',4''-tri-tert-butyl-terpyridine) as a ligand for nickel
      allows for the isolation of a Ni(I)-alkyl complex and a Ni(II)-alkyl halide
      complex, both of which can be used as mechanistic probes of key steps in alkyl
      cross-coupling reactions.

PMID- 16100607
TI  - A simple synthesis of mesoporous carbons with tunable mesopores using a colloidal
      template-mediated vapor deposition polymerization.
AB  - Mesoporous carbons with highly uniform and tunable mesopores were fabricated by
      one-step vapor deposition polymerization (VDP) using colloidal silica particles
      as templates and polyacrylonitrile (PAN) as a carbon precursor.

PMID- 16100608
TI  - Enantioselective allylation of ketones catalyzed by chiral In(III)-PYBOX
      complexes.
AB  - In the presence of 20 mol% of chiral catalytic complex prepared from In(OTf)3 and
      chiral PYBOX, allyltributylstannane reacted with achiral ketones to afford the
      corresponding homoallylic alcohols in moderate to high enantioselectivities (54
      95% ee), which constitutes the first example of enantioselective allylation of
      ketones catalyzed by the chiral In(III)-PYBOX complex.

PMID- 16100609
TI  - The synthesis of enantiomerically pure 4-substituted [2.2]paracyclophane
      derivatives by sulfoxide-metal exchange.
AB  - A general strategy for the synthesis of enantiomerically pure 4-substituted
      [2.2]paracyclophanes from a common sulfoxide precursor is described.

PMID- 16100610
TI  - The elusive phosphorescence of pyrromethene-BF2 dyes revealed in new
      multicomponent species containing Ru(II)-terpyridine subunits.
AB  - The triplet emitting state of an indacene at 774 nm (of 50 ms life-time) was
      observed for the first time in new ruthenium(II) complexes based on bipartite
      ligands carrying one or two indacene subunits linked via phenylethynyl connectors
      to terpyridine fragments.

PMID- 16100611
TI  - MCuB7O12.nH2O (M = Na, K ): a new copper borate with 14-ring channels.
AB  - The title compounds, which were synthesized in boric acid flux under mild
      conditions (493 K), contain a 14-member ring borate framework consisting of
      octahedral (CuO6), tetrahedral (BO4) and triangular (BO3) units.

PMID- 16100612
TI  - Solvolytic routes to new nonabismuth hydroxy- and alkoxy-oxo complexes:
      synthesis, characterization and solid-state structures of novel nonabismuth
      polyoxo cations Bi9(mu3-O)8(mu3-OR)6 5+ (R = H, Et).
AB  - Base hydrolysis of BiO(ClO4) yields ClO4- salts of the novel nonabismuth polyoxo
      cation Bi9(mu3-O)8(mu3-OH)6(5+); ethanolysis converts to the ethoxide Bi9(mu3
      O)8(mu3-OEt)6(5+).

PMID- 16100613
TI  - Ketonization of the remarkably strongly acidic elongated enol generated by flash
      photolytic decarboxylation of p-benzoylphenylacetic acid in aqueous solution.
AB  - Photodecarboxylation of p-benzoylphenylacetic acid in aqueous solution produces
      the elongated enol 5, whose strength as an oxygen acid (pQ(E/a)= 7.67) makes it
      more acidic than simple enol analogs by several orders of magnitude.

PMID- 16100614
TI  - Vibrational spectroscopy: a 'vanishing' discipline?
AB  - The aim of this tutorial review is to convince a broad readership that
      vibrational spectroscopy, although according to some vibrational spectroscopists
      seemingly less in focus nowadays than in days past, is far from 'dead'. It may
      seem to some that infrared and Raman spectroscopy are less in focus than in times
      past, despite the unique analytical capabilities. Vibrational spectroscopy is
      particularly powerful for non-destructive characterisation of substances,
      including living material. But compared to the past, a shift in applications has
      taken place, bringing new opportunities. This is partly due to the introduction
      of new features, including imaging and 2D correlation spectroscopy. Another
      factor is the recognition that vibrational spectroscopy can play a role in new
      rather than only in the traditional fields of application, e.g. new applications
      in the life-science field (living cells, cancer research), the characterisation
      of soil. But also the traditional application in catalysis sees new development
      within the context of Operando spectroscopy.

PMID- 16100615
TI  - Selective extraction of naturally occurring radioactive Ra2+.
AB  - Organic extractants play a significant role in the selective removal of
      radioactive cations from waste streams. Although, literature on the selective
      removal of man-made radioactive material such as Americium (Am) is widespread,
      the selective removal of naturally occurring radioactive material such as Ra2+ is
      only mentioned sporadically. This tutorial review deals with the selective
      extraction of the highly radiotoxic Ra2+. Special attention is paid to different
      types of organic extractants used.

PMID- 16100616
TI  - Coupling reactions of zirconocene complexes and heterosubstituted alkenes.
AB  - This tutorial review surveys recent advances in the field of zirconium promoted
      coupling reactions of unsaturated molecules (and/or organolithium compounds) and
      heterosubstituted alkenes. This reaction has recently emerged as a powerful tool
      in organic chemistry to access a variety of synthetically useful building blocks
      not easily available by other methods. In particular, three different reaction
      pathways are discussed: i) the reaction involving alkyne-zirconocene and aryne
      zirconocene complexes which allows access to dienyl and aryl zirconocene
      complexes; ii) the reaction of alkene-zirconocene complexes and enol ethers which
      has shown to be highly dependent on the structure of the enol ether used,
      allowing the synthesis of simple vinyl zirconocenes or multicomponent coupling
      products, and; iii) the reaction involving imine-zirconocene complexes which
      supposes a new entry to allylic amines.

PMID- 16100617
TI  - Thioglycosides in sequential glycosylation strategies.
AB  - This tutorial review surveys the use of thioglycosides in the development of
      sequential glycosylation methodologies, with a focus on chemoselective,
      orthogonal and iterative glycosylation strategies reported since the beginning of
      this century. Both fundamental aspects of glycosidic bond formation and ingenious
      state-of-the-art methodologies are presented.

PMID- 16100618
TI  - Proton, electron and energy transfer processes in excited phenol-olefin dyads.
AB  - Dyads containing phenol and olefin subunits are versatile models for the
      investigation of proton, electron and energy transfer processes. As they are
      readily accessible, a number of analogues (allylphenols, cinnamylphenols and
      derivatives) have been prepared with a wide range of photophysical and
      photochemical properties. By means of appropriate structural modification of a
      very simple initial structure, it is possible to reproduce, at will, different
      types of behaviour. In addition to providing valuable fluorescence emission data,
      these systems are chemically productive, giving rise to irreversible
      photoreactions that constitute a fingerprint for the mechanism involved. They
      include photocyclisation to 5- and 6-membered ring cyclic ethers, Z/E
      isomerisation, di-pi-methane rearrangement, formation of ortho-quinone methides,
      photohydration and photodehalogenation. This rich photochemistry is highly
      sensitive to the microenvironment experienced, as indicated by the dramatic
      modifications observed within cyclodextrin cavities. Intramolecular OH...pi
      interactions, both in their ground and excited states, play a key role in the
      interesting properties of 2-allylphenol derivatives. This is supported by
      experimental data and also by theoretical calculations.

PMID- 16100619
TI  - Dinitroso and polynitroso compounds.
AB  - The growing interest in the chemistry of C-nitroso compounds (RN=O; R = alkyl or
      aryl group) is due in part to the recognition of their participation in various
      metabolic processes of nitrogen-containing compounds. C-Nitroso compounds have a
      rich organic chemistry in their own right, displaying interesting intra- and
      intermolecular dimerization processes and addition reactions with unsaturated
      compounds. In addition, they have a fascinating coordination chemistry. While
      most of the attention has been directed towards C-nitroso compounds containing a
      single -NO moiety, there is an emerging area of research dealing with dinitroso
      and polynitroso compounds. In this critical review, we present and discuss the
      synthetic routes and properties of these relatively unexplored dinitroso and
      polynitroso compounds, and suggest areas of further development involving these
      compounds. (126 references.).

PMID- 16100621
TI  - Neonatal morbidity and decision-delivery interval in patients with uterine
      rupture.

PMID- 16100622
TI  - Sonographic measurement of the lower uterine segment thickness in women with
      previous caesarean section.
AB  - OBJECTIVES: To evaluate the accuracy of prenatal sonography in determining the
      lower uterine segment (LUS) thickness in women with previous Caesarean section
      and to assess the usefulness of measuring LUS thickness in predicting the risk of
      uterine rupture during a trial of vaginal birth. METHODS: Sonographic examination
      was performed in 102 pregnant women with one or more previous Caesarean sections
      at between 36 and 38 weeks' gestation to assess the LUS thickness, which was
      defined as the shortest distance between the urinary bladder wall-myometrium
      interface and the myometrium/chorioamniotic membrane-amniotic fluid interface. Of
      the 102 women examined, 91 (89.2%) had transabdominal sonography only, and 11
      (10.8%) had both transabdominal and transvaginal examinations. The sonographic
      measurements were correlated with the delivery outcome and the intraoperative LUS
      appearance. RESULTS: The mean sonographic LUS thickness was 1.8 mm, standard
      deviation (SD) 1.1 mm. An intraoperatively diagnosed paper-thin or dehisced LUS,
      when compared with an LUS of normal thickness, had a significantly smaller
      sonographic LUS measurement (0.9 mm, SD 0.5 mm, vs. 2.0 mm, SD 0.8 mm,
      respectively; P < 0.0001). Two women had uterine dehiscence, both of whom had
      prenatal LUS thickness of < 1 mm. Thirty-two women (31.4%) had a successful
      vaginal delivery, with a mean LUS thickness of 1.9 mm, SD 1.5 mm; none had
      clinical uterine rupture. A sonographic LUS thickness of 1.5 mm had a sensitivity
      of 88.9%, a specificity of 59.5%, a positive predictive value of 32.0%, and a
      negative predictive value of 96.2% in predicting a paper-thin or dehisced LUS.
      CONCLUSIONS: Sonography permits accurate assessment of the LUS thickness in women
      with previous Caesarean section and therefore can potentially be used to predict
      the risk of uterine rupture during trial of vaginal birth.

PMID- 16100623
TI  - Postpartum urinary and anal incontinence: a population-based study of quality of
      life of primiparous women in Quebec.
AB  - OBJECTIVE: To describe the quality of life of primiparous women with urinary or
      anal incontinence. METHODS: A questionnaire was mailed at six months postpartum
      to 2492 primiparous women living in Quebec. The prevalence of urinary
      incontinence was assessed at six months postpartum through the FPSUND severity
      score index; the prevalence of anal incontinence was assessed by the grading
      system of Vaizey et al.; the quality of life of women who developed incontinence
      was assessed using the Shumaker's I-QOL for urinary incontinence and Lowry's
      quality of life instrument for anal incontinence. Descriptive analysis, t-test,
      analysis of variance, and linear regression were used. RESULTS: The prevalence of
      urinary incontinence was 29.6% and of anal incontinence was 20.6%. Quality of
      life was affected significantly by the presence of urinary incontinence or both
      forms of incontinence (P 0.001) and by the type of urinary incontinence (P <
      0.001). Women with all types of anal incontinence had significantly lower quality
      of life scores for access to toilet (P < 0.001), lifestyle (P < 0.01), self
      esteem (P = 0.037), and total score (P < 0.001). Quality of life correlated with
      the severity of both urinary incontinence and anal incontinence: the more severe
      the urinary or anal incontinence, the lower the quality of life score.
      CONCLUSION: Women who have urinary or anal incontinence, or both, have
      significant reductions in indicators of quality of life. Research is needed to
      evaluate strategies for preventing and treating these problems.

PMID- 16100624
TI  - Does availability of fetal firbonectin testing in the management of threatened
      preterm labour affect the utilization of hospital resources?
AB  - OBJECTIVES: To examine how the availability of fetal fibronectin testing affects
      the utilization of hospital resources. METHODS: A comparison of the rates,
      duration, and costs of hospitalization for a prospective cohort of women who
      presented with preterm labour after fetal fibronectin (Ffn) testing became
      available, and a historical baseline cohort who presented with preterm labour
      before fetal fibronectin testing was available. The study included singleton
      pregnancies presenting between 24 and 34 weeks' gestation with signs and symptoms
      of preterm labour. The women in each study cohort presented during a designated
      20-week period. RESULTS: We examined the records of 116 subjects with comparable
      gestational age distributions in each 20-week period. During the study period
      when Ffn testing was available, 51 tests were performed. Four tests were invalid,
      and 12 subjects who were tested did not meeting the inclusion criteria.
      Admissions for preterm labour in the study period were significantly less than in
      the baseline cohort (12.1% vs. 24.1%, P = 0.03), with no difference in preterm
      births (8.6% vs. 7.8%). The mean length of stay per patient with preterm labour
      declined from 5.2 days to 0.6 days (P < 0.0001), and the mean cost per patient
      with preterm labour declined from $3666 to $581 (P < 0.0001). In the 20-week
      study period, there was a reduction in total length of hospital stay from 145 to
      28 days, with an overall reduction in total cost from $102 660 to $26 169.
      CONCLUSION: The availability of Ffn testing was associated with a reduction in
      hospital admissions, length of hospital stay, and overall hospital costs in the
      management of threatened preterm labour.

PMID- 16100625
TI  - A puzzling intrauterine death: non-compaction of the fetal ventricular myocardium
      presenting with reversed end-diastolic flow velocity in the umbilical arteries.
AB  - BACKGROUND: Absent or reversed end-diastolic flow velocity (ARED) in the
      umbilical arteries is typically associated with severe intrauterine growth
      restriction (IUGR), although there may be other causes, such as aneuploidy. CASE:
      A healthy 30-year-old gravida 2, para 0 woman with an uneventful pregnancy and
      normal prenatal screening test results presented with sudden cessation of fetal
      movement at 26 weeks' gestation. Ultrasound demonstrated unexplained ARED with
      normal fetal growth and normal amniotic fluid volume. The fetus died during
      transfer to the labour and delivery unit. The cause of fetal demise was initially
      assumed to be feto-maternal hemorrhage, but postmortem examination revealed non
      compaction of the ventricular myocardium. CONCLUSION: Intrinsic myocardial
      disease should be considered in the differential diagnosis when ARED is
      discovered in the umbilical arteries, especially when fetal growth is normal.
      Postmortem examination should be performed even if a prior 18- to 20-week
      anatomical ultrasound has been reported as normal.

PMID- 16100626
TI  - Successful pregnancy after amniotic fluid embolism: a case report.
AB  - BACKGROUND: Amniotic fluid embolism (AFE) has a mortality rate of 60% to 80% and
      accounts for approximately 10% of all maternal deaths in the United States.
      Although AFE is thought to be an anaphylactoid reaction, there are few reports of
      subsequent pregnancy after AFE. CASE: A healthy 29-year-old underwent an
      uncomplicated planned Caesarean section for her third pregnancy. She had a
      history of placental abruption with the first pregnancy and amniotic fluid
      embolism with the second pregnancy, for which she was treated with blood products
      and recovered fully. CONCLUSION: This case of a 29-year-old woman with successful
      subsequent pregnancy after amniotic fluid embolism and a limited number of case
      reports in the literature suggest that AFE is a sporadic event.

PMID- 16100627
TI  - Motherisk rounds. Warfarin embryopathy following low-dose maternal exposure.

PMID- 16100628
TI  - Gynaecological and obstetric management of women with inherited bleeding
      disorders.
AB  - OBJECTIVE: The prevalence of bleeding disorders, notably von Willebrand disease
      (vWD), among adult women with objectively documented menorrhagia is consistently
      reported to be 10% to 20% and is even higher in adolescents presenting with
      menorrhagia. This consensus document has been developed by a multidisciplinary
      committee consisting of an anesthesiologist, 2 hematologists, and an
      obstetrician/gynaecologist and has been endorsed by their relevant specialty
      bodies. It has been prepared with the express purpose of providing guidelines for
      both women with inherited bleeding disorders and for their caregivers regarding
      the gynaecological and obstetric management of these women, including appropriate
      anesthesia support where indicated. OPTIONS: Diagnostic tools and specific
      medical and, where appropriate, surgical alternatives to management are reviewed
      and evidence-based recommendations presented. EVIDENCE: A MEDLINE search of the
      English literature between January 1975 and November 2003 was performed using the
      following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand,
      congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral
      contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural,
      spinal. Recommendations from other society guidelines were reviewed.
      RECOMMENDATIONS: 1. Inherited bleeding disorders should be considered in the
      differential diagnosis of all patients presenting with menorrhagia (II-2B). The
      graphical scoring system presented is a validated tool which offers a simple yet
      practical method that can be used by patients to quantify their blood loss (II
      2B). 2. Because underlying bleeding disorders are frequent in women with
      menorrhagia, physicians should consider performing a hemoglobin/hematocrit,
      platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women
      who have a personal history of other bleeding or a family history of bleeding,
      further investigation should be considered, including a vWD workup (factor VIII,
      vWF antigen, and vWF functional assay) (II-2B). 3. Treatment of menorrhagia in
      women with inherited bleeding disorders should be individualized (III-B). 4. An
      inherited bleeding disorder is not a contraindication to hormonal therapy (oral
      contraceptives [II-1B], depot medroxyprogesterone acetate (DMPA) [II-3B], danazol
      [II-2B], GnRH analogs [II-3B]) or local treatments (levonorgestrel-releasing IUS
      [II-1B]) and non-hormonal therapy (antifibrinolytic drug tranexamic acid [II-1B])
      as well as desmopressin (II-1B). These therapies represent first line treatment.
      Blood products should not be used for women with mild bleeding disorders (III-A).
      5. In women who no longer want to preserve their fertility, conservative surgical
      therapy (ablation) and hysterectomy may be options (III-B). Clinicians may
      consult the "SOGC Clinical Practice Guideline: Guidelines for the Management of
      Abnormal Uterine Bleeding" for an in-depth discussion of the available
      therapeutic modalities, both medical and surgical. To minimize the risk of
      intraoperative and post-operative hemorrhage, coagulation factors should be
      corrected preoperatively with post-operative monitoring (II-1B). 6. Girls growing
      up in families with a history of vWD or other inherited bleeding disorders should
      be tested pre-menarchally to determine whether or not they have inherited the
      disease to allow both the patient and her family to prepare for her first and
      subsequent menstrual periods (III-C). 7. In adolescents presenting with
      menorrhagia, an inherited bleeding disorder should be excluded (III-B). When
      possible, investigation should be undertaken before oral contraceptive therapy is
      instituted, as the hormonally induced increase in factor VIII and vWF may mask
      the diagnosis (II-B). 8. Pregnancy in women with inherited bleeding disorders may
      require a multidisciplinary approach. A copy of their recommendations should be
      given to the patient and she should be instructed to present it to the health
      care provider admitting her to the birthing centre. Women with severe bleeding
      disorders or with a fetus at risk for a severe bleeding disorder should deliver
      in a hospital (level three) or where there is access to consultants in
      obstetrics, anesthesiology, hematology, and pediatrics (III-C). 9. Vacuum
      extraction, forceps, fetal scalp electrodes, and fetal scalp blood sampling
      should be avoided if the fetus is known or thought to be at risk for a congenital
      bleeding disorder. A Caesarean section should be performed for obstetrical
      indications only (II-2C). 10. Epidural and spinal anesthesia are contraindicated
      if there is a coagulation defect. There is no contraindication to regional
      anesthesia if coagulation is normalized. The decision to use regional anesthesia
      should be made on an individual basis (III-C). 11. The risk of early and late
      postpartum hemorrhage is increased in women with bleeding disorders. Women with
      inherited bleeding disorders should be advised about the possibility of excessive
      postpartum bleeding and instructed to report this immediately (III-B). 12.
      Intramuscular injections, surgery, and circumcision should be avoided in neonates
      at risk for a severe hereditary bleeding disorder until adequate
      workup/preparation are possible (III-B). The quality of evidence reported in this
      document has been described using the Evaluation of Evidence criteria outlined in
      the Report of the Canadian Task Force on the Periodic Health Exam (Table 1).

PMID- 16100629
TI  - What I will want when I'm a patient.

PMID- 16100630
TI  - 2004 Shanghai international workshop of fetal macrosomia and adult obesity.

PMID- 16100631
TI  - Prevalence, management, and outcomes of preterm prelabour rupture of the
      membranes of women in Canada.
AB  - OBJECTIVES: To determine the prevalence of preterm prelabour rupture of the
      membranes (PPROM) at Canadian university-affiliated perinatal referral centres,
      to assess the different management strategies, and to review neonatal outcomes.
      METHODS: Twelve Canadian university-affiliated perinatal referral centres
      provided information on their management of PPROM, and 9 participated in data
      collection to determine prevalence. All women presenting with PPROM during a 2
      week period were observed until delivery, and obstetric and neonatal outcome data
      were subsequently obtained. The total number of deliveries in each centre was
      recorded for the same time period. We also determined the incidence of PPROM and
      the neonatal outcome for all women presenting with PPROM at the Kingston General
      Hospital from January 1999 to December 2001 by retrospective chart review.
      RESULTS: In the 9 academic centres, 27 women (1 with a twin pregnancy) presented
      with PPROM during the 2-week period. There were 1168 deliveries during the same
      time period, giving a prevalence of PPROM of 2.3%. Overall, 53% of placentas
      submitted for histopathology after PPROM demonstrated evidence of
      chorioamnionitis. In the retrospective chart review, we found 153 cases of
      confirmed PPROM from January 1999 to December 2001,an incidence of 2.8%. Clinical
      management in all centres was similar for most women who presented with PPROM
      prior to 34 weeks' gestation. Management after 34 weeks' gestation varied among
      the 12 centres, ranging from immediate induction of labour to expectant
      management and induction at a greater gestational age (GA). CONCLUSIONS: The
      increased neonatal morbidity associated with PPROM appears to be inversely
      related to GA. Increased risk of chorioamnionitis is related to increased time
      from PPROM to delivery.

PMID- 16100632
TI  - Safety and community: the maternity care needs of rural parturient women.
AB  - OBJECTIVE: To investigate rural parturient women's experiences of obstetric care
      in the context of the social and economic realities of life in rural, remote, and
      small urban communities. METHODS: Data collection for this exploratory
      qualitative study was carried out in 7 rural communities chosen to represent
      diversity of size, distance to hospital with Caesarean section capability and
      distance to secondary hospital, usual conditions for transport and access, and
      cultural and ethnic subpopulations. We interviewed 44 women who had given birth
      up to 24 months before the study began. RESULTS: When asked about their
      experiences of giving birth in rural communities, many participants spoke of
      unmet needs and their associated anxieties. Self-identified needs were largely
      congruent with the deficit categories of Maslow's hierarchy of needs, which
      recognizes the contingency and interdependence of physiological needs, the need
      for safety and security, the need for community and belonging, self-esteem needs,
      and the need for self-actualization. For many women, community was critical to
      meeting psychosocial needs, and women from communities that currently have (or
      have recently had) access to local maternity care said that being able to give
      birth in their own community or in a nearby community was necessary if their
      obstetric needs were to be met. CONCLUSION: Removing maternity care from a
      community creates significant psychosocial consequences that are imperfectly
      understood but that probably have physiological implications for women, babies,
      and families. Further research into rural women's maternity care that considers
      the loss of local maternity care from multiple perspectives is needed.

PMID- 16100633
TI  - Complementary and alternative medicine in gynaecologic oncology.
AB  - OBJECTIVES: To explore complementary and alternative medicine (CAM) use among
      gynaecologic oncology patients in Nova Scotia. METHODS: Over a 3-month period,
      163 patients were asked to fill out a questionnaire concerning CAM. Those
      entering the study provided demographic information such as age, address, and
      employment status, as well as medical information and details of their use of
      alternative therapies. RESULTS: A total of 152 patients were entered into the
      study, giving a response rate of 93.3%. Of these, 116 had used at least one type
      of CAM, classifying them as users (76.3%). Women who considered themselves "more
      religious" were more likely to be CAM users (P = 0.001). There were no
      significant differences found between users and nonusers with respect to other
      patient characteristics reported. Patients with cervical cancer were less likely
      to use CAM than participants with another primary gynaecological malignancy (P =
      0.040). The most frequent CAM therapy practised was spirituality/prayer (52.6%).
      Most women used CAM to improve their physical well-being, and 53.3% of the women
      were interested in receiving more information on CAM. CONCLUSION: A significant
      number of women undergoing conventional treatment for gynaecologic cancer in
      Halifax, Nova Scotia, also use CAM. Women are using CAM for numerous reasons and
      believe they are benefiting from CAM in many ways. Physicians need to be aware of
      this high usage rate and should explore their patients' attitudes to and opinions
      about CAM.

PMID- 16100634
TI  - Obstetric ultrasound: is it time for informed consent?

PMID- 16100635
TI  - Obstetric ultrasound biological effects and safety.
AB  - OBJECTIVE: To review the biological effects and safety of obstetric ultrasound.
      OUTCOME: Outline the circumstances in which safety may be a concern with
      obstetric ultrasound. EVIDENCE: Medline was searched, and a review of a document
      on this subject published by Health Canada and of bibliographies from identified
      articles was conducted. VALUES: Review by principal authors and the Diagnostic
      Imaging Committee of the SOGC. The level of evidence was judged as outlined by
      the Canadian Task Force on the Periodic Health Examination. BENEFITS, HARMS, AND
      COSTS: Obstetric ultrasound should only be done for medical reasons, and exposure
      should be kept as low as reasonably achievable (ALARA) because of the potential
      for tissue heating. Higher energy is of particular concern for pulsed Doppler,
      colour flow, first trimester ultrasound with a long transvesical path (> 5 cm),
      second or third trimester exams when bone is in the focal zone, as well as when
      scanning tissue with minimal perfusion (embryonic) or in patients who are
      febrile. Operators can minimize risk by limiting dwell time, limiting exposure to
      critical structures, and following equipment generated exposure information.
      Recommendations 1. Obstetric ultrasound should only be used when the potential
      medical benefit outweighs any theoretical or potential risk (II-2A). 2. Obstetric
      ultrasound should not be used for nonmedical reasons, such as sex determination,
      producing nonmedical photos or videos, or for commercial purposes ( III-B). 3.
      Ultrasound exposure should be as low as reasonably achievable (ALARA) because of
      the potential for tissue heating when the thermal index exceeds 1. Exposure can
      be reduced through the use of output control and (or) by reducing the amount of
      time the beam is focused on one place (dwell time) (II-1A). 4. All diagnostic
      ultrasound devices should comply with the output display standards (MI and TI)
      (III-B). 5. When ultrasound is done for research or teaching purposes, exposed
      individuals should be informed if either the MI or TI are greater than 1 and how
      this exposure compares to that found in normal diagnostic practice (III-B). 6.
      While imaging the fetus in the first trimester, Doppler and colour Doppler should
      be avoided (III-B).

PMID- 16100636
TI  - Ultrasound evaluation of first trimester pregnancy complications.
AB  - OBJECTIVE: To review the biological effects and safety of obstetric ultrasound.
      OUTCOME: Outline the circumstances in which safety may be a concern with
      obstetric ultrasound. EVIDENCE: Medline was searched, and a review of a document
      on this subject published by Health Canada and of bibliographies from identified
      articles was conducted. VALUES: Review by principal authors and the Diagnostic
      Imaging Committee of the SOGC. The level of evidence was judged as outlined by
      the Canadian Task Force on the Periodic Health Examination. BENEFITS, HARMS AND
      COSTS: Obstetric ultrasound should only be done for medical reasons, and exposure
      should be kept as low as reasonably achievable (ALARA) because of the potential
      for tissue heating. Higher energy is of particular concern for pulsed Doppler,
      colour flow, first trimester ultrasound with a long transvesical path (> 5 cm),
      second or third trimester exams when bone is in the focal zone, as well as when
      scanning tissue with minimal perfusion (embryonic) or in patients who are
      febrile. Operators can minimize risk by limiting dwell time, limiting exposure to
      critical structures, and following equipment generated exposure information.
      Recommendations 1. Obstetric ultrasound should only be used when the potential
      medical benefit outweighs any theoretical or potential risk (II-2A). 2. Obstetric
      ultrasound should not be used for nonmedical reasons, such as sex determination,
      producing nonmedical photos or videos, or for commercial purposes ( III-B). 3.
      Ultrasound exposure should be as low as reasonably achievable (ALARA) because of
      the potential for tissue heating when the thermal index exceeds 1. Exposure can
      be reduced through the use of output control and (or) by reducing the amount of
      time the beam is focused on one place (dwell time) (II-1A). 4. All diagnostic
      ultrasound devices should comply with the output display standards (MI and TI)
      (III-B). 5. When ultrasound is done for research or teaching purposes, exposed
      individuals should be informed if either the MI or TI are greater than 1 and how
      this exposure compares to that found in normal diagnostic practice (III-B). 6.
      While imaging the fetus in the first trimester, Doppler and colour Doppler should
      be avoided (III-B).

PMID- 16100637
TI  - Fetal soft markers in obstetric ultrasound.
AB  - OBJECTIVE: To evaluate ultrasound "soft markers" used in fetal genetic screening.
      OPTIONS: Ultrasound screening at 16 to 20 weeks is one of the most common genetic
      screening and (or) diagnostic tests used during pregnancy. The practical concern
      for ultrasound screening is false-positive and false-negative (missed or not
      present) results. The use and understanding of ultrasound soft markers and their
      screening relative risks is an important option in the care of pregnant women.
      Currently, the presence of a "significant" ultrasound marker adds risk to the
      likelihood of fetal pathology, but the absence of soft markers, except in
      controlled situations, should not be used to reduce fetal risk. OUTCOMES: The use
      of ultrasound in pregnancy has significant health and economic outcomes for
      families and the health care system, compared with no ultrasound use. The Society
      of Obstetricians and Gynaecologists of Canada (SOGC) recommends a single
      "routine" ultrasound evaluation at 16 to 20 weeks in all pregnancies. Patients
      need to be counselled about the positive and negative findings that ultrasound
      may reveal so they are prepared for unexpected pregnancy knowledge and the
      possibility of further testing options being offered. EVIDENCE: Committee members
      were asked to review specific soft marker ultrasound topics after consensus was
      reached on the most commonly published soft markers. Medline and PubMed databases
      were searched for peer-reviewed English articles published from 1985 to 2003.
      Reviews of each soft marker topic were written by committee members with quality
      of evidence and classification of recommendations. These reviews were then
      circulated and discussed by the combined committee. Final format for the
      guideline was completed by the committee chairpersons. VALUES: The quality of
      evidence and classification of recommendations followed discussion and consensus
      by the combined committees of Diagnostic Imaging and Genetics of the SOGC.
      BENEFITS, HARMS AND COSTS: It is not possible at this time to determine the
      benefits, harms, and costs of the guideline because this would require health
      surveillance and research and health resources not presently available; however,
      these factors need to be evaluated in a prospective approach by provincial and
      tertiary initiatives. Consideration of these issues is in the options and outcome
      section of this abstract. RECOMMENDATIONS: 1. The screening ultrasound at 16 to
      20 weeks should evaluate 8 markers, 5 of which (thickened nuchal fold, echogenic
      bowel, mild ventriculomegaly, echogenic focus in the heart, and choroid plexus
      cyst) are associated with an increased risk of fetal aneuploidy, and in some
      cases with nonchromosomal problems, while 3 (single umbilical artery, enlarged
      cisterna magna, and pyelectasis) are only associated with an increased risk of
      nonchromosomal abnormalities when seen in isolation (II-2 B). 2. Identification
      of soft markers for fetal aneuploidy requires correlation with other risk
      factors, including history, maternal age, and maternal serum testing results (II
      1 A). 3. Soft markers identify a significant increase in fetal risk for genetic
      disease. Timely referral for confirmation, counselling, and investigation is
      required to maximize management options (III-B). VALIDATION: Peer-reviewed
      guideline development is part of the committee process in addition to SOGC
      council and editorial review.

PMID- 16100638
TI  - Access to maternity care.

PMID- 16100639
TI  - Perinatel outcomes of singleton pregnancies achieved by in vitro fertilization: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To determine whether the incidence of adverse obstetric outcomes is
      higher in singleton pregnancies achieved by in vitro fertilization (IVF) than in
      spontaneously conceived singletons matched for maternal age. METHODS: We used
      comprehensive search strategies to search MEDLINE and EMBASE databases. We
      selected case-control and cohort studies that compared singleton pregnancies
      conceived by IVF or intracytoplasmic sperm injection (ICSI) with spontaneously
      conceived singletons (matched for maternal age [case-control studies] or
      controlled for maternal age [cohort studies]). Two reviewers independently
      assessed titles, abstracts, and study quality and extracted data. Statistical
      analysis was performed with Review Manager for Windows (Version 4.2, Oxford, UK).
      We performed meta-analysis of dichotomous data, using odds ratios (ORs) as
      measures of effect size, with a random effects model. We followed the Meta
      Analysis of Observational Studies in Epidemiology (MOOSE) guidelines for meta
      analysis of observational studies. RESULTS: Singleton pregnancies resulting from
      IVF have increased rates of poor obstetric outcome, compared with spontaneously
      conceived singletons matched for maternal age, with increases in perinatal
      mortality (OR 2.40; 95% confidence interval [CI] 1.59-3.63), preterm birth at <
      33 weeks' gestation (OR 2.99; 95% CI 1.54-5.80), preterm birth at < 37 weeks'
      gestation (OR 1.93; 95% CI 1.36-2.74), very low birth weight (< 1500 g) (OR 3.78;
      95% CI 4.29-5.75), small for gestational age (OR 1.59; 95% CI 1.20-2.11), and
      congenital malformations (OR 1.41; CI 1.06-1.88). CONCLUSIONS: IVF singleton
      pregnancies have increased rates of poor obstetric outcome, compared with
      spontaneously conceived singletons matched for maternal age.

PMID- 16100640
TI  - Maternity care by family physicians: characteristics of successful and
      sustainable models.
AB  - OBJECTIVE: To provide examples of sustainable and rewarding models of maternity
      care that can help reduce the attrition of family practitioners from intrapartum
      maternity care practice. METHODS: We surveyed a cohort of family physicians
      providing maternity care in primary care settings, using various models, to
      determine how each model handled the challenges of this practice. RESULTS:
      Different models of care are effective; there is no single best model of family
      practice maternity care. Successful models provide care for a substantial volume
      of patients, have call schedules that are appropriate for the volume of patients
      and number of participating physicians, have protocols for patient management,
      and have flexible and compatible clinic members. CONCLUSION: Structured sign-out
      models of care that incorporate innovative models for funding assist many family
      physicians in Canada in continuing to provide maternity care. Family medicine
      residents must be encouraged to incorporate these models of maternity care into
      their future practices.

PMID- 16100641
TI  - Prenatal and congenital syphilis in British Columbia.
AB  - OBJECTIVE: To describe the incidence of maternal syphilis and the corresponding
      rate of infection in exposed neonates in British Columbia before and after a
      serious outbreak of infectious syphilis in the heterosexual population. METHODS:
      We conducted a retrospective chart review of pregnant women with positive
      syphilis serology and reported cases of congenital syphilis in British Columbia
      from 1994 to 2003. Clinical charts were reviewed for demographic information,
      staging of maternal syphilis, and stage of pregnancy when treatment was received.
      The primary outcome measure was the number of cases of congenital syphilis. We
      conducted a 2-sided z-test and Fisher's exact test to determine differences in
      the proportion of infectious syphilis in mothers and the number of cases of
      congenital syphilis before and during the major outbreak. RESULTS: In 389 478
      live births in British Columbia between 1994 and 2003, 77% of mothers had
      prenatal syphilis serology. A diagnosis of syphilis was made in 183 mothers,
      resulting in 5 cases of congenital syphilis. Four of these were in infants whose
      mothers did not undergo prenatal syphilis testing. The proportion of pregnant
      women with infectious syphilis was significantly higher after the onset of a
      major outbreak of syphilis in the community than it was before (P = 0.001), but
      there was no significant difference in the number of cases of congenital syphilis
      (3 before and 2 after the outbreak, P = 0.36). CONCLUSION: Although syphilis
      rates in British Columbia during the study period rose steadily, the prevalence
      of congenital syphilis remained low. Our findings suggest that, in the context of
      a major outbreak, universal screening and prenatal syphilis testing may
      contribute to controlling rates of congenital syphilis.

PMID- 16100642
TI  - NovaSure bipolar radiofrequency endometrial ablation: report of 200 cases.
AB  - OBJECTIVE: To review the perioperative complications and short-term outcome in
      women undergoing endometrial ablation for menorrhagia using the NovaSure bipolar
      radiofrequency impedance-controlled system. METHODS: We conducted a prospective
      observational study of endometrial ablation using the NovaSure system in 200
      women with menorrhagia not amenable to medical management. RESULTS: Of the 200
      women treated, 146 have been observed for 1 to 4 years with the following
      outcomes related to menstrual bleeding: amenorrhea 43.1%, light bleeding 41.8%,
      normal bleeding 4.1%, and heavy bleeding 11%. Twelve of the 146 women (8.2%)
      required repeat surgical treatment: hysterectomy in 10 cases and repeat ablation
      in 2. In the 200 cases, 1 laparoscopy was performed because of uterine
      perforation at the time of pretreatment hysteroscopy, and 2 patients required
      antibiotic therapy for postoperative endomyometritis. Of the women observed for 1
      to 4 years, 81.5% felt the procedure was successful, and 97.3% would recommend
      the procedure to a friend. CONCLUSION: Endometrial ablation using the NovaSure
      system is a simple technique in the normal uterine cavity, which can be performed
      under local anaesthesia and conscious sedation. The complication rate is low, and
      the short-term satisfaction and results are good.

PMID- 16100643
TI  - Laparoscopy and reported pain among patients with endometriosis.
AB  - OBJECTIVE: To compare the effectiveness of sharp excision of endometriosis with
      sham surgical excision in alleviating endometriosis-associated pain for up to 1
      year following surgery. METHODS: Patients requiring a laparoscopy for severe
      pelvic pain were eligible. If endometriosis was visually identified at
      laparoscopy, a biopsy of a representative lesion was taken. The women were then
      randomized either to have all remaining endometriosis excised with laparoscopic
      scissors (the excision group) or to have no further surgical treatment (the
      control group). Patients were asked to complete daily pain scales for 1 month
      preoperatively and quarterly for 1 year postoperatively. Subjects were blinded to
      their treatment allocation for 1 year. RESULTS: Twenty-nine women underwent
      laparoscopy and biopsy and were randomized to have excision or no treatment of
      endometriosis. The excision and control groups were similar in age, parity, and
      revised American Society for Reproductive Medicine stage of disease. Sixteen
      women completed the full year of follow-up: 9 in the excision group, and 7 in the
      control group. Overall, recorded pain was significantly reduced at 1 year (P <
      0.05), with no significant difference between the excision and control groups.
      CONCLUSION: Laparoscopy with diagnostic biopsy alone is associated with a
      significant reduction in pain for up to 1 year postoperatively. Although the
      study lacked sufficient statistical power to exclude an effect of excision, pain
      relief in each group was similar. These results indicate a potential benefit of
      sham surgical procedures in assessing novel surgical interventions.

PMID- 16100644
TI  - Is an interdisciplinary session on ethics and law in obstetrics and gynaecology
      effective?
AB  - OBJECTIVE: To evaluate the effects of an interdisciplinary session on medical
      ethics and legal issues related to obstetrics and gynaecology on medical
      students' knowledge, attitudes, and behaviours. METHODS: Second-year medical
      students at the University of Alberta were asked to complete surveys before and
      after an interdisciplinary panel session on ethics and legal issues in
      reproductive health. Survey questions were related to knowledge of ethics and
      law, attitudes toward controversial topics in reproductive health, and predicted
      behaviours in specific clinical scenarios. In the postsession survey, students
      were asked to evaluate the session's usefulness and impact. RESULTS: Fifty-seven
      students completed both the pre- and postsession surveys. Most students listed
      family, religion, culture, peer groups, scientific thought and theory, and school
      and education as influences on their own personal ethics and morality. Fifty-five
      students (97%) stated that the panel session was useful. Most students (79%)
      reported that the session increased their knowledge of ethical and legal issues
      in reproductive health. Many students felt that the panel session would change
      the way they practise in similar clinical situations (63%). The panel session
      appeared to affect knowledge and predicted behaviour. CONCLUSION: A large-group
      interdisciplinary panel session can influence medical students' knowledge and
      future behaviours related to ethics and law in obstetrics and gynaecology.
      Medical students gave this session a high rating.

PMID- 16100645
TI  - Breast cancer and abortion.

PMID- 16100646
TI  - Postural health in women: the role of physiotherapy.
AB  - OBJECTIVE: To advise obstetric and gynaecology care providers of the physical,
      psychological, and environmental factors that affect women's posture throughout
      their lifespan, from adolescence to menopause. To outline the physiotherapy
      management of obstetrics, osteoporosis, and urinary incontinence in women and to
      identify recommendations for referral to a physiotherapist. OUTCOMES: Knowledge
      of abnormal postures, contributing factors and recommendations for physiotherapy
      management. EVIDENCE: MEDLINE, PEDro, and Cochrane Library Search from 1992 to
      2003 for English-language articles and references from current textbooks related
      to posture and women's health conditions that are managed by physiotherapists.
      VALUES: The evidence collected was reviewed by the authors and quantified using
      the evaluation of evidence guidelines developed by the Canadian Task Force on the
      Periodic Health Exam. RECOMMENDATIONS: 1. Pelvic floor muscle training with a
      physiotherapist is recommended to prevent urinary incontinence during pregnancy
      and after delivery (I-A). 2. Core stability training with a physiotherapist is
      recommended to prevent and treat back and pelvic pain during and following
      pregnancy (I-B). 3. Physiotherapist-prescribed exercises are recommended for
      women to elicit positive changes in bone mass and to reduce fall and fracture
      risk (I-A). 4. Pelvic floor muscle training with a physiotherapist is recommended
      for women with stress urinary incontinence (I-A). The Canadian Physiotherapy
      Association and Society of Obstetricians and Gynaecologists of Canada have
      developed this joint policy statement regarding posture in women's health that
      highlights the physical, psychological, and environmental factors that affect
      women's posture throughout their lifespan, from adolescence to menopause. This
      statement outlines the role of physiotherapy in the assessment and treatment of
      women's posture; outlines the physiotherapy management of obstetrics,
      osteoporosis, and urinary incontinence; and identifies recommendations for
      referral to a physiotherapist. The quality of evidence and classification of
      recommendations have been adapted from the Report of the Canadian Task Force on
      the Periodic Health Exam (Table 1).1.

PMID- 16100647
TI  - Grand rounds: what is the point?
AB  - INTRODUCTION The chalkboards are no longer only chalkboards but are PowerPoint
      presentations. Textbooks are rarely texts but rather CDs to be downloaded at a
      reader's discretion; and classrooms are almost optional. Still the university
      hospital environment reflects a belief in the pedagogic effectiveness of the 19th
      century medical wisdom by encouraging and maintaining grand rounds. What makes
      the grand rounds is debatable. The large crowds, which historically attended to
      hear and to feast on a specialist's pearls of wisdom, have been replaced by
      sparse crowds often inattentive and in a rush to be elsewhere. This survey was
      designed to assess the status of the grand round in Canada. We contacted the 16
      medical schools via e-mail and asked either the chairperson or the obs-gyn grand
      round coordinator to respond to a 2-page questionnaire. The Association of
      professors of Obstetrics and Gynecology (APOG) assisted in diffusing and
      collecting the data.

PMID- 16100648
TI  - The evaluation of soluble Fas and soluble Fas ligand levels of bronchoalveolar
      lavage fluid in lung cancer patients.
AB  - Fas-Fas Ligand (FasL) is one of the major mediator system that activates
      programmed cell death. Cleavage of membranebound FasL by a metalloproteinase-like
      enzyme resulted in the formation of soluble FasL (sFasL). sFasL as well as the
      transmembrane form of FasL binds to Fas and transduces apoptotic signal in Fas
      expressing cells. It's suggested that soluble Fas (sFas) and sFasL has an impact
      on tumor progress and immune escape feature of tumor cells from the host immune
      system. Since Fas antigen expression in the lungs has been localized to alveolar
      and bronchial epithelial cells, in this study we aimed to investigate the sFas
      (pg/mL) and sFasL levels (pg/mL) of bronchoalveolar lavage (BAL) fluid in lung
      cancer patients. Study population was consisted of 27 patients with lung cancer
      (mean age 62.9 +/- 10.7 years, 25 control subjects (mean age 47.9 +/- 13.9
      years). BAL was performed under local anesthesia, on the unaffected lung of
      patients; either subsegments of right middle or lingula. BAL sFas and sFasL were
      evaluated by using ELISA method. The mean levels of sFas was 60.8 +/- 56.8 in
      lung cancer patient and 39.5 +/- 25.9 in control subjects (p> 0.05). The mean
      levels of sFasL was 51.6 +/- 39.2 in cancer patient and 41.2 +/- 27.4 in control
      subjects (p> 0.05). In conclusion, although we did not observe any significant
      difference between two groups, higher BAL levels of sFas and sFasL levels in lung
      cancer patients than control subjects, made us thought that apoptosis might have
      a role development and progression of lung cancer.

PMID- 16100649
TI  - Lung cancer histopathology in the Thrace region of Turkey and comparison with
      national data.
AB  - Following the trends in lung cancer (LC) morbidity and mortality rates can show
      past trends of cigarette smoking and can give clues on some geographical factors.
      The demographics of LC patients and the histopathologic distribution of their
      disease in the Thrace region of Turkey have yet to be defined. A retrospective
      chart review of primary LC patients admitted to the pulmonology department of
      Trakya University Hospital between 1992 and 2001 was performed. Charts were
      available for review in 521 of 567 patients. The mean age was 61 +/- 10 years (30
      86 years) and 497 (95.4%) patients were male (male/female ratio= 20.7). When
      compared with national and international data, male/female ratio for the LC
      patients from Thrace region was higher than the ratio found from Turkey in
      general and also from other countries. Adenocarcinoma (ADC) was present in seven
      of the 24 (29.2%) of the females and prevalence of ADC was more than 2.5 times in
      females than males (p< 0.05). Squamous cell types were more common in males.
      Histopathological type did not vary with age in females, but small cell carcinoma
      was more prevalent in males under the age of 45 (44.7% if . 45 years old vs.
      29.1% if > 45 years old, p< 0.05). These data may support that the LC associated
      with smoking is in the earlier phase of the epidemic in Thrace region. Monitoring
      the LC trend in our region can give clues on evolving cigarette design and
      smoking attitudes and geographic factors.

PMID- 16100650
TI  - [Retrospective analysis of patients with small cell lung cancer treated at Gazi
      University Department of Radiation Oncology].
AB  - The combination of radiotherapy (RT) and chemotherapy (CT) is the main treatment
      modality of limited-stage small cell lung cancer (SCLC). The application of
      radiation timing, doses, fraction schedules in this modality and the indication
      of prophylactic cranial irradiation is recently controversial. In this
      retrospective study, these subjects were evaluated by considering our patients
      results. Seventy patients having adequate data for examination with limited-stage
      SCLC were referred to our clinic in the period between December 1995 and December
      2002. The patients were classified according to their response to CT, the dose
      and timing of RT applications. The effects of obtained variables on overall
      survival were analyzed. Male/ female ratio was 5/1; and the mean age was 55 years
      (range 31-80 years). The mean follow-up of all patients was 10 months and the
      mean survival time was 16 months. An objective (complete and partial) response to
      CT administered before RT was seen in 47 (67%) patients. The survival time was
      better in the CT responding patients (median 11 months versus 6 months, p=
      0.002). The application of more than 50 Gy radiation dose was found to be
      ineffective on survival. An improvement in survival was observed in RT
      application beginning before fourth cycle CT (median 14 months versus 8 months p=
      0.01). In despite of the ineffectiveness of prophylactic cranial irradiation on
      survival is observed in survival analysis, it was found to be a parameter
      affecting survival in Cox-regression analysis. However the most frequently
      complication during RT was oesophagitis. Grade III was seen in 1 (3%) patient.
      The response to CT can be accepted as an indicator for survival. We concluded
      that the administering of RT in the beginning of CT, not administering radiation
      doses of more than 50 Gy and the necessity of applying prophylactic cranial
      irradiation to all patients showing complete response are points to be considered
      according to our retrospective analysis.

PMID- 16100651
TI  - [Evaluation of silicosis in ceramic workers].
AB  - This study is aimed to evaluate the incidence of silicosis and the relation of it
      with personal and work-related factors among workers exposed to silica in ceramic
      factory. Workers were evaluated by respiratory symptoms, physical examination,
      pulmonary function and radiological findings. Occupational and Enviromental
      Pulmonary Disease Evaluation Questionnaire of the Turkish Thoracic Society
      Enviromental and Occupational Pulmonary Diseases Working Group was used. 365 of
      626 workers had exposure to silica and the rest 261 were concerned as control
      group. There was no difference between mean age, duration of work and smoking
      pack year among the groups (p> 0.05). Cough and sputum rates were higher in
      silicosis group FEV1 and FVC values were lower in silica group but this was not
      statistically significant. When the two subgroups of silica group (the workers in
      high dust concentration and the ones in low concentration) were compared, the
      high concentrated group had significantly more sputum but the other symptoms and
      pulmonary functional parameters were not different significantly. 24 workers had
      parenchymal densities adjusted with pneumoconiosis. The workers with the
      pneumoconistic finding, had a higher mean age and longer duration of work. As a
      conclusion, ceramic industry has risk for silicosis. And the risk increase by
      time and age.

PMID- 16100652
TI  - [Evaluation of IHA, ELISA and Western Blot tests in diagnosis of pulmonary cystic
      hidatidosis].
AB  - Pulmonary cystic hidatidosis caused by the larval stages of Echinococcus
      granulosus is a common parasitic disease in Turkey and throughout the world. In
      this study IHA, ELISA and Western Blot (WB) tests were performed with a panel of
      59 sera from 31 surgically confirmed pulmonary cystic hidatidosis patients, 18
      patients with pulmonary disease other than cystic hidatidosis and 10 healthy
      individual. The overall sensitivity of the IHA, ELISA and WB tests used for the
      serodiagnosis of pulmonary cystic hidatidosis were found as 96.7%, 87.1%, 100%
      and the specificities were 82.2%, 89.2% and %85.7, respectively. Using the WB
      test 8-12 kDa, 24 kDa and 124 kDa bands were detected as valuable for surgically
      confirmed patients' sera. One or more of these bands were also detected in sera
      of four patients with other pulmonary diseases false-positively. In conclusion
      conventional serologic test like IHA and ELISA is valuable in diagnosis of
      pulmonary cystic hidatidosis, also evaluation of some specific bands in WB would
      contribute to the diagnosis.

PMID- 16100653
TI  - [Adenosquamous carcinoma of the lung (an analysis of 13 cases)].
AB  - Adenosquamous carcinoma of the lung is a rare disease. The biological behavior
      and clinicopathologic characteristics of this tumor have not been well described.
      In this study, we retrospectively evaluated 13 patients with adenosquamous
      carcinoma of the lung diagnosed at our center between January 2001 and May 2004.
      There were 12 males and 1 female whose ages ranged from 45 to 69 years, with a
      mean age of 55.9 years. Ten patients were smoker. The most frequent symptoms were
      chest pain and cough. Bronchoscopic examination detected that tumor was centrally
      located in four cases and was peripherally located in nine cases. Preoperative
      pathological diagnosis was squamous cell carcinoma in eight patients, non-small
      cell lung carcinoma in four patients and adenocarcinoma in one patient. One
      patient was in pathological stage IA, three patients in stage IB, one patient in
      stage IIA, two patients in stage IIB, five patients in stage IIIA, and one
      patient in stage IIIB. Twelve patients underwent resection (six, lobectomy; five,
      pneumonectomy; one, bilobectomy). Five of 12 patients received adjuvant therapy.
      Five patients died of disease within 3 and 21 months. Seven patients have had
      survival time between 9 and 31 months.

PMID- 16100654
TI  - [Idiopathic chronic eosinophilic pneumonia: a case report].
AB  - Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare cause of chronic lung
      disease in children and adolescents. We described four-years old boy presenting
      with recurrent pneumonia and symptoms of bronchial asthma. Because of peripheral
      eosinophilia and bilateral pulmonary infiltrates patient investigated
      comprehensive and chronic eosinophilic pneumonia determined histopathologically.
      Other conditions causing eosinophilic pneumonia were ruled out. He showed a
      dramatic response to oral corticosteroid therapy. This report emphasizes that
      ICEP should be considered in pediatric age group on a cause for chronic hypoxemi
      or intractable symptoms of respiratory system.

PMID- 16100655
TI  - A rare association: Castleman's disease and pemphigus vulgaris.
AB  - Castleman disease is a reactive lymph node hyperplasia of unknown origin that
      often involving the thorax although it may involve all parts of the body. It is
      usually seen in young adults and presents an asymptomatic course. It is usually
      located to anterior and middle mediastinum. Pemphigus vulgaris is a bullous skin
      disease in which immune mechanisms take place in the pathogenesis. Mouth and
      oropharynx are the most commonly involved structures. IgG antibodies against the
      epidermal intracellular structures are essential in the diagnosis. We have wanted
      to discuss a 28 years old female with the literature review since the association
      between pemphigus vulgaris and Castleman's disease is rare.

PMID- 16100656
TI  - [Association of combined small cell and large cell lung cancer with Lambert-Eaton
      myasthenic syndrome: case report].
AB  - Lambert-Eaton myasthenic syndrome (LEMS) is a rare type of neuromusculer
      conduction disorder. This disease can be seen with lung cancer and, it is
      associated with otoimmunity. Among the symptoms of lung cancer LEMS can be seen,
      but it is very rare. In this case, LEMS symptoms were analyzed before lung cancer
      symptoms. The localization of the tumor was near the pulmonary artery. By the
      early diagnose, the patient had the chance of cure.

PMID- 16100657
TI  - A case of a small cell lung carcinoma presenting with jaundice due to pancreatic
      metastasis.
AB  - Though the high incidence of pancreatic metastasis of lung cancer has been
      reported in autopsy series, symptomatic cases with jaundice due to that is very
      rare. Dominant histological type with pancreatic metastases is small cell
      carcinoma and prognosis is poor. Hereby, we report a case initially presenting
      with gastroenterologic symptoms as jaundice, nausea, vomiting, weight loss and
      abdominal pain and then diagnosed as primary small cell carcinoma of the lung
      with metastasis to pancreas. He underwent a palliative surgery due to obstructive
      jaundice. This presented case is a rare one with its priority of
      gastroenterologic symptoms rather than pulmonary complaints.

PMID- 16100658
TI  - Pseudohypoxemia: interpretation of discrepancies between SaO(2) and SpO(2).
AB  - Pulse oximetry is an important tool in evaluation and management of patients with
      cardiopulmonary disease. It provides an accurate, continuous, non-invasive
      measurement of oxygenation, however it has some limitations. Pseudohypoxemia is
      an artifactual condition that has been reported in patients with extreme
      leukocytosis and thrombocytosis. It should be suspected in patients with a
      discrepancy between oxygen saturation measured by pulse oximetry and that in
      arterial blood. High level of suspicion is needed to diagnose this condition as
      not doing so may lead to unnecessary escalation of therapy (i.e., increased
      levels of oxygen and mechanical ventilation). We provide a review of the
      principles and limitations of pulse oximetry and discuss the pathophysiology and
      diagnosis of pseudohypoxemia.

PMID- 16100659
TI  - [Treatment in diffuse interstitial lung diseases].
AB  - Diffuse interstitial lung diseases are parenchymal diseases of the lung with many
      various etiologies and most of which are idiopathic. The mainstays of the
      treatment are corticosteroids and immunosuppressants. This paper deals with the
      treatment of idiopathic interstitial pneumonias and sarcoidosis.

PMID- 16100660
TI  - Smoking and lung cancer.
AB  - Nowadays, around one-third of adults are known to be smokers, and smoking rates
      are increasing among the female population. It is estimated that deaths
      attributable to tobacco use will rise to 10 million by 2025, and one-third of all
      adult deaths are expected to be related to cigarette smoking. The association
      between cigarettes and lung cancer has been proven by large cohort studies.
      Tobacco use has been reported to be the main cause of 90% of male and 79% of
      female lung cancers. 90% of deaths from lung cancer are estimated to be due to
      smoking. The risk of lung cancer development is 20-40 times higher in lifelong
      smokers compared to non-smokers. Environmental cigarette smoke exposure and
      different types of smoking have been shown to cause pulmonary carcinoma. DNA
      adducts, the metabolites of smoke carcinogens bound covalently with DNA, are
      regarded as an indicator of cancer risk in smokers. In recent decades, there has
      been a shift from squamous and small cell lung cancer types to adenocarcinoma,
      due to increasing rates of smoking among female population and rising light
      cigarette usage. After smoking cessation, the cumulative death risk from lung
      cancer decreases. Patients who continue smoking experience greater difficulties
      during cancer treatment. Stopping smoking may prolong survival in cancer
      patients, and also decreases the risk of recurrent pulmonary carcinoma. In order
      to save lives and prevent smoking related hazards, physicians should advise both
      healthy individuals and those with cancer of the benefits of stopping smoking.

PMID- 16100661
TI  - [Preoperative evaluation in surgical treatment of lung cancer].
AB  - The most effective treatment option of a patient with lung cancer is lung
      resection. The most important problem in this modality of treatment is
      postoperative complications. In order to decrease the mortality and morbidity, it
      is necessary to predict potential complications with cardiopulmonary evaluation.
      In this review, we reviewed the methods to assess cardiac and pulmonary functions
      of a patient undergoing lung resection under the lights of recent literature.

PMID- 16100662
TI  - Finite element method based stress analysis of zone I and zone II sacral
      fractures.
AB  - BACKGROUND: Sacral bone fractures after direct traumas such as gunshot wounds and
      blunt sacral traumas are rarely, whereas those occurring after indirect traumas
      with vertical shear mechanisms ( car accidents or falls) are more frequently
      seen. METHODS: A cadaver sacrum was modelled 3-dimensionally using finite element
      software. Left sacroiliac joint was modeled to simulate a 75- kg man falling on
      one leg from a height of 5 meters. An impact load of 10 kN was transferred to the
      sacrum via intervertebral disc surface and two facets. Von Mises equivalent
      stress distribution was estimated. RESULTS: Von Mises stress distribution was
      calculated for sacral ala (430 MPa), S1 pedicle (225 MPa), and S1 lamina (35
      MPa). Stress values were 200 Mpa, 130 Mpa, 105 Mpa, and 55 MPa on ventrolateral,
      dorsomedial, ventromedial and dorsolateral sides of S1 foramen respectively.
      Vertical shear injury caused stress distribution to concentrate at sacral ala and
      S1 pedicle (zone I). Local stress distribution around S1 foramen is concentrated
      ventrolaterally CONCLUSION: High incidence of zone I sacral fractures and low
      incidence of neurological deficits could be explained by concentration of stress
      at sacral ala. Zone II fractures might be due to by transfer of triggered
      stresses from sacral ala and S1 pedicle to ventrolateral side of S1 foramen.

PMID- 16100663
TI  - [Early diagnosis of colorectal anastomotic leakages by detection of bacterial
      genome].
AB  - BACKGROUND: Microbial infections and translocation of intestinal bacteria are
      thought to contribute to multiple system organ failure, but bacterial cultures
      are often negative in patients with this complication. The purpose of this study
      was to determine the sensitivity of PCR for detecting microbial DNA in the blood
      of animals after conducting an experimental model of anastomotic leakage.
      METHODS: Fourty rats were divided into three groups as follows: Control Group;
      simple laparotomy group, Anastomosis Group; colon resection and anastomosis
      group, and Leakage Group; group with colon resection and an anastomosis leaving a
      5 mm opening. Blood was drawn form rats before the procedure, and postoperative
      3rd and 6th days. DNAs were extracted from these samples and PCR techniques were
      used to amplify genes of Escherichia coli. Statistical analysis for the
      percentage of rats with microbial DNA in the blood for all groups was done by
      Fisher's exact chi- square test. The difference among groups was considered
      significant if the P value was less than 0.05. RESULTS: Most of the detected
      Escherichia coli genes were from the Leakage Group, and the detection rate was
      significant compared to other groups. CONCLUSION: We suggest that PCR could be a
      useful adjunct tool for immediate diagnosis of anastomotic leakages.

PMID- 16100664
TI  - [The effect of selective bowel decontamination and mechanical bowel preparation
      on bacterial translocation due to intraabdominal hypertension].
AB  - BACKGROUND: The objective of our study is to evaluate the preventive effects of
      selective digestive decontamination (SDD) and mechanical bowel preparation in
      rats with experimentally induced bacterial translocation. METHODS: Fourty adult
      male Sprague Dowley rats weighing 250-300 g. were divided equally into four
      groups as Group 1 (sham [control]), Group 2 (experimentally induced IAH at 19
      mmHg), Group 3 ( SDD group) and Group 4 (SDD and mechanical bowel preparation
      with 19 mmHg intraabdominal pressure). Group 3 and 4 were treated at 12 hours
      intervals with oral gentamycine 5 mg/kg and IM sefotaxime 100mg/kg Mechanical
      bowel preparation was performed by oral administration of sodium phosphate. After
      24 hours all rats were sacrified; mesenteric lymph nodes, spleen and liver biopsy
      specimens were harvested aseptically. Specimens were diluted and cultured in
      McConkey medium and the colony-forming units (CFU/gr ) were calculated. RESULTS:
      In Kruskal Wallis tests there were no significant differences between Group 1 and
      3 or 4, and also Group 3 and 4 (p>0.05, p=0.872 respectively), while differences
      between Group 1 and 2, and also Group 3 and 4 were statistically significant
      (p<0.001) with respect to CFU/g estimates. CONCLUSION: These data indicate that
      selective intestinal decontamination and mechanical bowel preparation prevent
      bacterial translocation due to intraabdominal hypertension.

PMID- 16100665
TI  - [A statistical analysis for the identification of factors effecting prognosis of
      civilian patients with cranial gunshot wounds].
AB  - BACKGROUND: Patients with civil cranial gunshot injuries who were treated in our
      hospital were statistically analyzed for the factors acting on 7 days survival
      and prognosis without regarding treatment modalities. MATERIAL AND METHOD:
      Patients were divided into two groups according to the mortality rates in 7 days
      following the trauma without regarding treatment modalities. Initial GCS score,
      pupillary response to light, coagulopathy, ventricular penetration and number of
      hemispheres affected are 5 differentials evaluated separately and in combination
      for their effects on mortality rates within 7 days posttraumatically and their
      statistical significance. RESULTS: Thirty six male (75%) and 12 female (25%)
      patients included in the study. Total and 7 day- survival rates were 27% (13/48),
      and 31% (15/48) respectively. Among GCS scores, pupillary defects, coagulopathy,
      intraventricular penetration, the number of hemispheres affected, the most
      important prognostic factors of the patients living less than 7 days were found
      to be primarily coagulopathy and then pupillary defects. The other variables were
      not significantly effective and the results were in accordance with the
      literature. CONCLUSION: In civilian patients with cranial gunshot injuries
      pupillary defect and coagulopathy were statistically significant prognostic
      factors. We think that aggressive medical and surgical treatment will be
      beneficial even if the patients' neurological status is deteriorating.

PMID- 16100666
TI  - [In situ pinning on slipped femoral capital epiphysis with a single cannulated
      screw].
AB  - BACKGROUND: Slipped femoral capital epiphysis requires immediate surgical
      intervention. Because this condition is relatively rare, the diagnosis is
      frequently delayed in patients with complaints of knee and hip pain and limping.
      Middle term results of patients who were diagnosed early and treated with a
      single cannulated screw are evaluated. MATERIAL AND METHOD: Five hips of 4
      patients (3 male, 1 female) with slipped femoral capital epiphysis treated with a
      single cannulated screw between the years of 2000-2003 were evaluated under the
      light of literature findings. RESULTS: Mean patient age was 13 (range 12-14)
      years; mean slip angle was 33.2 degrees (range 26 degrees -40 degrees ); mean
      body mass index was 27.3 kg/m2 (range 25.6-29.8 kg/m2 ). After immediate
      immobilization, internal fixation with a single screw was applied without any
      reduction. CONCLUSION: During the mean follow-up period of 24 months (range 12-
      41) epiphysial slipping progression was not observed and new epiphysial slipping
      did not develop on the contralateral hips. We are of the opinion that
      intervention for slipped femoral capital epiphysis with a single cannulated screw
      is a beneficial treatment. Although the number of our cases is limited we believe
      a close follow-up of the hip without prophylactic pinning should be the
      preferable alternative.

PMID- 16100667
TI  - [Indications for computed tomography in patients with mild head injuries].
AB  - BACKGROUND: To identify clinical parameters that may be associated with
      intracranial lesions in patients with mild head injuries, Glasgow Coma Scale
      (GCS) scores of 15 but without any focal neurological deficit. METHODS: All head
      trauma patients admitted to the emergency room within 3 months with GCS scores of
      15 (n = 371) were evaluated. Patients with focal neurological deficits,
      penetrating or multiple traumas, gun shot wounds were not evaluated. RESULTS:
      Mean age of 222 male and 149 female patients was 22.4 years. Frequency of
      intracranial lesions detected in CT was higher in patients older than 60 years of
      age. A significant difference was not found between both genders. Detection rate
      of abnormalities was higher after motorway accidents. Loss of consciousness and
      post-traumatic fits were associated with higher rates of pathological sequelae. A
      significant difference was not found between patients with or without headache,
      nausea, and vomiting. Sensitivity and specificity of cranial x-ray were estimated
      to be 38.2% and 93.2% when compared with cranial CT respectively. CONCLUSION: The
      incidence of intracranial lesions in patients with mild head injuries, GCS scores
      of 15, younger than 60 years of age, and without any focal neurological deficits,
      loss of consciousness, post-traumatic fits, gun shot wound, and penetrating
      injury is 0.6%.

PMID- 16100668
TI  - [Screw-wire combination technique in the reconstruction of anterior mandible
      fractures].
AB  - BACKGROUND: Fractures of the mandible are among frequently seen facial injuries
      and their reconstruction requires unique procedures. The purpose of this study is
      to demonstrate the efficacy of screw-wire combination osteosynthesis technique in
      the treatment of simple and displaced, symphisis and parasymphisis mandible
      fractures. METHODS: In our clinic 9 simple and displaced, symphysis and
      parasymphysis fractures of mandible were treated with screw-wire combination
      osteosynthesis technique. By intraoral approach 4 screws were applied to both
      sides of the fracture site 5 mm away from either side placed at superior (n = 2)
      and inferior (n = 2) localizations. Lower and upper wires were placed
      bicortically, and unicortically respectively . In order to surround them with
      wire, the screws were not fully tightened. After surrounding the screws, the
      wires were tightened in a manner that would properly face the fracture sites
      mutually. Intermaxillary fixation was applied for 7 to 10 days in all patients.
      RESULTS: During follow up period we did not encounter infection, malunion,
      nonunion, delayed union and patient discomfort necessitating extirpation of the
      materials fixed. CONCLUSION: We think that screw-wire combination technique is an
      easy and effective method with low cost and fast healing especially in
      reconstruction of anterior mandible fractures.

PMID- 16100669
TI  - The effect of delayed admission in burn centers on wound contamination and
      infection rates.
AB  - BACKGROUND: Since wound infection rates in patients with delayed admission seemed
      to be significantly higher, a retrospective study of bacteriology in 320 burn
      patients, over a 5-year period was carried out in order to analyze the relation
      between delayed admission and wound infection rates in our Burn unit of Uludag
      University, Faculty of Medicine. METHODS: The patients were separated into
      moderate or major burn groups according to burn severity. Wound infection and
      contamination frequencies were analyzed according to time-delay between burn
      injury and hospitalization time. RESULTS: Delayed admission was found to be an
      important factor that causes an increase in wound infection and contamination
      frequency. This increase was significant especially among patients with moderate
      burn wounds. In patients with severe burns, wound infection and contamination
      frequencies were found to be higher for all admission time points. CONCLUSION:
      Systemic antibiotic prophylaxis should be discussed in patients with moderate
      burns whose admission-delay is more than 78 hours. Wound infection and
      contamination rates were high in patients with major burns independent of the
      admission time. Therefore, systemic antibiotic prophylaxis should also be
      discussed in this group of patients, although it results in elimination of the
      normal skin flora.

PMID- 16100670
TI  - [Diagnostic value of pediatric trauma score in blunt abdominal injuries].
AB  - BACKGROUND: It was reported that pediatric trauma score (PTS) is an important
      tool for the initial assessment of injury severity and could help in the triage
      of injured children as well. The aim of this study is to investigate the
      prognostic value of PTS in blunt abdominal traumas. METHODS: Between 1997 and
      2003, children with blunt abdominal trauma who treated in the Department of
      Pediatric Surgery, Trakya University Medical Faculty were evaluated with
      retrospective analysis. PTS was designated for each case. Individual morbidity
      and mortality were correlated with PTS. Data analysis were performed with Mann
      Whitney U test and ROC curve statistically. RESULTS: Seventy five patients were
      included in this study. The mean age of children was 7.5+/-4.2 years (10 months
      15 years). Mechanisms of injury were as follows: automobile versus pedestrian 30,
      falls 18, motor vehicle crashes 14, bicycle accidents 7 and others 6. Forty two
      abdominal organ injuries were found.. PTS of the patients who had abdominal
      injuries were different statistically from others (p<0.05). On the ROC curve
      sensitivity and specificity were found as %74 and %12 respectively in those with
      PTS scores of 8. CONCLUSION: PTS was found to be of low sensitivity and
      specificity for blunt abdominal trauma patients.

PMID- 16100671
TI  - A rare case of splenic infarct presenting with acute abdominal pain due to
      polyarteritis nodosa: case report and review of the literature.
AB  - A 44 year-old man presented to the Emergency Department of American Hospital with
      severe pain persisting in the left upper quadrant for several hours. A computed
      tomographic scanning (CT scan) and celiac digital substraction angiography (DSA)
      of the abdomen demonstrated a splenic infarct. Histopathological examinations
      showed diffuse acute vasculitis, thrombosis, panvasculitis which led us to
      diagnose the case as "polyarteritis nodosa". The diagnosis is usually difficult
      to establish and it is usually delayed due to variable clinical manifestations
      dependent on the site and the extent of arterial involvement.

PMID- 16100672
TI  - [A descending colon tumour prolapsing from anus: case report].
AB  - Most colonic polyps are asymptomatic and the incidence rises during sixth and
      seventh decades. Symptoms and signs may vary with histological types and
      location. Clinical features include fresh rectal bleeding, mucoid diarrhea and
      prolapsus of stalked rectal polyps located near distal segment. Here we discuss a
      case with a rare clinical presentation, who had sessile malign villous adenoma
      located in the descending colon, which caused colocolic intussusception and
      prolapsed through the anus.

PMID- 16100673
TI  - [Global cerebral ischemic findings in a woman who attempted to commit suicide by
      hanging].
AB  - We will discuss clinical and radiological findings of a woman who attempted
      suicide by hanging. We report a 19-year-old women attempted suicide by hanging
      herself. There was no known period of global brain ischemia. She had a score of 7
      on the Glasgow coma scale. CT scan showed bitemporal hippocampal atrophy and
      SPECT showed non-activated area on right temporal and temporo-occipital regions.
      There has been few reports relating to the involvement of the brain as documented
      on CT and SPECT. Hanging leads to global hypoxic damage resulting in hypo
      perfusion changes mainly cerebral in temporal lobes and atrophy.

PMID- 16100674
TI  - [Juguler vein gunshot injury from blank cartridges].
AB  - Blank cartridge guns, which are produced for self-defence needs and considered
      harmless, can be easily purchased by adults due to lack of legal regulations. We
      present this case because injuries caused by gunshot from blank cartridges may be
      fatal and are rarely encountered in emergency departments. A 3-year-old boy was
      brought to the emergency department since he had a wound on his neck caused
      accidentally by gunshot from blank cartridges. He had a moderate general
      condition and pale appearance. There was an irregular-edged, defective wound 2 cm
      above the sternal notch in midline localization with a dimension of 3 x 4 cm.
      Computed tomography of the thorax revealed contusion in the apex of the left
      lung. A 2-mm plastic piece embedded in the left internal jugular vein was removed
      during the operation. A mass education on danger and harm of these guns as well
      as legal regulations for restricted use seem to be necessary. Also, physicians
      should keep in mind that blank cartridge guns can cause fatal injuries.

PMID- 16100675
TI  - [Free radial forearm flap transfer for the reconstruction of the Achilles tendon
      and soft tissue defect: a case report].
AB  - Reconstruction of the soft tissue defects around the Achilles tendon is a
      difficult challenge. This condition traditionally has been treated with staged
      procedures. We report a case treated with a one stage procedure. A
      neuromusculocutaneous radial forearm free flap was used for the reconstruction of
      an achilles tendon and for covering the overlying large soft tissue defect caused
      by a gun shot injury. The defect on the Achilles tendon was 15 cm in length and
      soft tissue loss was 18 x 10 cm. The flap including flexor carpi radialis muscle
      tendon was applied over the Achilles tendon. A terminolateral arterial
      anostomosis was performed on the tibialis posterior artery. There was no
      complication except a mild superficial infection on the lateral side of the flap
      treated by antibiotherapy. A satisfactory functional result was obtained.
      Application of a free neuromusculocutaneous radial forearm composite flap is a
      good technique to cover achilles tendon and soft tissue defects and to restore
      the function as a one stage procedure.

PMID- 16100676
TI  - More appropriate vaccines.

PMID- 16100677
TI  - Medicinal chemistry of neurodegenerative diseases--fourth international
      symposium. 30 January-2 February 2000, Cancun, Mexico.

PMID- 16100678
TI  - Australian Neuroscience Society--20th Annual Meeting. 30 January-2 February 2000,
      Melbourne, Australia.
AB  - This meeting presented a large array of high quality neuroscience research, some
      of which held possible relevance for therapeutic development. The potential use
      of multipotent neural stem cells harvested from adult brain for transplantation
      and regeneration therapy was highlighted, as was the increasingly central role of
      the p75 neurotrophin receptor in regulating neuronal cell death. Of particular
      interest were strategies for the prevention of neuronal death by systemic
      administration of p75 receptor antisense oligonucleotides. Other significant data
      included a possible synergy between prostaglandin receptors and opioid receptors
      in cellular responses, thought to underlie pain perception and opioid analgesia.
      Groups in Melbourne, Brisbane and Bath, UK, have isolated novel alpha-conotoxins
      from Conus marine snails, and characterized their effects on neuronal nicotinic
      acetylcholine receptors (nAChRs), highlighting their subunit specificity and
      effects on synaptic transmission. While none of these findings are close to
      effective clinical use as yet, they hold great promise for the future,
      underlining the necessity for basic research as a starting point for novel
      therapies.

PMID- 16100679
TI  - Dermatology--24th Hawaii Seminar. 7-12 February 2000, Big Island, HI, USA.
AB  - At this seminar, several encouraging developments were demonstrated in various
      areas of dermatology practice. Much attention was focused on topical tacrolimus,
      the US approval of which, for the treatment of atopic dermatitis is much
      anticipated. The general consensus from trials was that the drug is safe and
      effective, and it is hoped that it will be of use in pediatric cases. Additional
      data were presented regarding the use of cyclosporin in psoriasis patients, with
      some evidence that low doses could be delivered safely with adequate monitoring.
      Safety was an issue in many of the sessions, reflecting the increasing
      involvement of potentially toxic therapies within dermatology. The debate
      regarding the use of topical tretinoin during pregnancy continues, and
      pharmacokinetic evidence was presented to demonstrate that systemic absorption of
      the drug is minimal. The range of diseases treated by topical imiquimod may be
      expanded with data suggesting that it may have benefits in the treatment of basal
      cell carcinomas. Surgical dermatology also featured heavily in the meeting,
      reflecting the more interventional approaches favored by dermatologists today.

PMID- 16100680
TI  - New trends in clinical and experimental immunosuppression--fourth international
      conference. 17-20 February 2000, Geneva, Switzerland.
AB  - The meeting covered several aspects of currently used immunosuppressive drugs,
      but focused on tolerance induction strategies in the treatment of both allograft
      rejection and autoimmune diseases. Topics discussed included: clinical trials
      with anti-CD3 in recently-diagnosed insulin-dependent diabetes mellitus (IDDM)
      patients; Tr1 cells in bone-marrow transplantation; and, 1 alpha,25
      dihydroxyvitamin D3-associated with mycophenolate mofetil and anti-CD25 in islet
      transplantation. In addition, malononitrilamides, an emerging class of novel
      immunosuppressants, were discussed in depth.

PMID- 16100682
TI  - Apoptosis modulators: targeting cellular suicide.

PMID- 16100681
TI  - Millennium Pharma Summit--strategic planning to increase growth and generate
      pharmaceutical shareholder value. 26-27 January 2000, London, UK.
AB  - With mergers and acquisitions (M&As) being the 'watch words' of the moment among
      those involved in the pharmaceutical industry, this meeting aimed to bring
      together the senior hierarchy of both medium and big pharma to discuss the issues
      pertinent to competitive survival and shareholder profit delivery. Along with a
      more objective analysis delivered by a number of management consultancy
      representatives, the summit presented delegates with interesting and often
      controversial viewpoints on: strategic partnerships and alliances; developing
      organizational models to generate profitability; the promotion of innovative R&D
      to maximize shareholder value; the development of marketing strategies in line
      with increasing consumer power; and, past, present and future consequences for
      the industry as a result of 'merger mania'.

PMID- 16100683
TI  - Monobactams as enzyme inhibitors.

PMID- 16100684
TI  - Matrix metalloproteinase inhibitors in cancer: an update.

PMID- 16100685
TI  - Factor Xa inhibitors (Berlex).
AB  - Berlex Biosciences is investigating several series of Factor Xa inhibitors aimed
      at the prevention and treatment of thrombotic disorders [297584]. Some compounds
      are based on the structure of ZK-805412, a Z,Z-2,7
      bis(dibenzylidene)cycloheptanone, which showed nanomolar Factor Xa inhibitor
      potency [301618]. Specific inhibitors identified in the program include ZK-806350
      and ZK- 807191. Other series include condensed diphenoxypyridines, indoles,
      benzimidazoles and carbazoles [279707,279714,297584, 279710,279716,279718]. The
      inhibitory activity of 2,6-diphenoxypyridines on Factor Xa has been demonstrated
      in vitro [328787]. Berlex and Warner-Lambert are collaborating on Factor Xa
      inhibitors [347062].

PMID- 16100686
TI  - TCH-346 (Novartis).
AB  - TCH-346, an anti-apoptotic compound, is under development by Novartis for the
      potential treatment of Parkinson's disease (PD) and motor neuron disease
      [271447,342937]. By September 1999, phase I clinical trials for PD were underway
      [342937]. The compound was discovered in a screen for molecules with both
      norepinephrine uptake and MAO inhibiting properties but, although it had anti
      apoptotic properties, it did not inhibit MAOA or MAO-B [333136,332004]. The
      compound increases lifespan in the progressive motorneuropathy mouse model and
      prevents ischemia in models of ischemia and seizure [288893]. In vivo, it shows
      neurorescuing and anti-apoptotic properties in PC12 cells and cerebellar granule
      cells, among others, at concentrations of 0.1 pM to 10 microM, suggesting that
      its action might prove potentially useful against Alzheimer's and/or Parkinson's
      disease [332004]. The compound has also shown neurorescuing properties in rat
      pups after axotomy, rat hippocampal CA1 neurons after transient ischemia/hypoxia
      and mouse nigral dopaminergic (DA) neurons after treatment with MPTP in doses
      ranging between 0.0003 and 0.1 mg/kg po or sc, depending on the model [333136].
      Data presented by the University of Nijmengen and the Free University of
      Amsterdam show that TCH-346 improves the behavioral and enzymatic outcome in the
      rat 6-OH-dopamine model of Parkinson's disease. TCH-346 (0.0014 mg/kg sc bid)
      prevented abnormal stepping (open field test) and prevented increases in fore and
      hind-paw retraction time. TCH-346 also improved acquisition in the Morris water
      maze task and, at doses between 0.0014 and 0.14 mg/kg, prevented reduction in
      tyrosine hydroxylase immunoreactivity [345259]. Affinity binding studies with TCH
      346 showed that GAPDH is the target [294902,283200]. Differential display RT-PCR
      also showed that protein-isoaspartyl-methyl transferase is induced by the drug
      [283200].

PMID- 16100687
TI  - BIO-1211 (Biogen).
AB  - Biogen, in collaboration with Merck & Co, is developing late activator VLA-4
      (alpha4beta1) integrin antagonists for the potential treatment of inflammatory
      conditions [271194]. Merck has begun phase II trials with the lead compound, BIO
      1211, for asthma, Biogen is still conducting preclinical research for its
      designated indications [317648,319225]. Under the collaborative agreement, each
      company has worldwide rights to certain indications; Merck has rights for asthma
      and Biogen retains the rights to a number of smaller indications, including
      multiple sclerosis, inflammatory bowel disease, renal indications and most
      diseases in which the US patient population is less than 200,000 [271194]. VLA-4
      inhibitors show anti-inflammatory action by inhibition of binding between
      adhesion factors and leukocytes, but with no loss of basophil function, and they
      have the advantage of specificity not seen with existing drugs [273417]. In
      February 1999, Lehman Brothers predicted 40% probabilities that the compound
      would reach the US and ex-US markets for the asthma indication (Merck), and
      launch onto these markets by 2003. Peak annual sales of US dollar 500 million
      (US) and US dollar 500 million (outside US) are predicted, both in 2010 [319225].

PMID- 16100688
TI  - Promises and pitfalls of therapeutics to modify oxidant balance in chronic
      disease.

PMID- 16100689
TI  - British Pharmacological Society Cambridge Symposia. 5-7 January 2000, Cambridge,
      UK.
AB  - This meeting covered a broad range of pharmacological topics, although the main
      themes were covered in four mini-symposia. This report concentrates on the
      cannabinoid, pain and cardiac ischemia symposia. The cannabinoid system was
      identified as a major area of potential therapeutic interest, offering a number
      of clinical targets that may be modified through the actions of selective
      ligands. Novel approaches to the treatment of neurogenic pain, where conventional
      analgesics have limited value, are being explored with significant success. The
      role of delayed preconditioning in cardiac ischemia was also addressed as a
      mechanism of cardioprotection.

PMID- 16100691
TI  - Therapeutic control of angiogenesis--IBC Conference. 17-18 January, 2000, London,
      UK.

PMID- 16100690
TI  - British Pharmacological Society Cambridge Symposia. Pharmacology for the next
      millennium. 5-7 January 2000, Cambridge, UK.
AB  - The Winter Meeting 2000 of the British Pharmacological Society at Cambridge
      University provided the usual high attendance. This was reflected in the
      approximately 300 poster and oral communications presented during the course of
      the 3 days, with a high number contributed by the host institution. The
      conference comprised three symposia including 'Pharmacology for the next
      millennium' chaired by Professor Alan Cuthbert, recently retired Head of the
      Department of Pharmacology in Cambridge. This symposium attracted a prestigious
      array of internationally renowned speakers, with new information relating to the
      H3 histamine receptor which has a growing list of potential therapeutic
      indications. New information regarding screening methodologies, therapeutics for
      analgesia, schizophrenia and Alzheimer's disease were also reported.

PMID- 16100692
TI  - ECPI's Second Annual Pharmacogenomics Event. 18-20 January 2000, London, UK.

PMID- 16100693
TI  - Advances in anti-arthritic agents. 24-25 January 2000, London, UK.
AB  - This meeting provided an excellent overview of the field of arthritis, although
      most of the drugs mentioned were designed to treat rheumatoid arthritis. There
      was an air of excitement surrounding the event because, after a substantial
      period of dormancy in clinical rheumatology, there are now many promising new
      treatments emerging, which, it is hoped, will greatly improve the quality of life
      for numerous arthritis sufferers. Speakers covered topics as diverse as care for
      sufferers, impact of the disease, status of current treatments, and approaches
      for the future. The majority of the presentations were drug-oriented; the speaker
      generally gave a summary of their company's arthritis research program and then
      followed this with a case study of its lead compound.

PMID- 16100694
TI  - Nucleic acid therapeutics--millennium conference. 8-11 January 2000, Clearwater
      Beach, FL, USA.

PMID- 16100695
TI  - Chase H&Q--18th Annual Healthcare Conference. 10-13 January 2000, San Francisco,
      CA, USA.
AB  - The Chase H&Q Healthcare Conference is held annually in January and provides an
      excellent opportunity to obtain an overall impression of the state of the
      pharmaceutical and biotechnology industry. Chase H&Q's flagship Healthcare and
      Technology conferences have become the primary checkpoints for major growth stock
      investors to gauge the pulse of entire industry groups as well as particular
      companies. The 17th Annual Healthcare Conference attracted approximately 235
      companies and 3300 total attendees. This year, more than 240 companies from
      biotechnology, life science, medical products, healthcare service and healthcare
      internet industries, were presented in five parallel sessions at the 18th Annual
      Healthcare Conference, which was attended by over 3500 delegates. As the
      conference was directed primarily at analysts, there was little in the way of
      reporting of 'grass roots' science. This report focuses on some of the companies
      who have made great strides during 1999, and for whom 2000 looks set to be a
      challenging and exciting year.

PMID- 16100697
TI  - Tuberculosis vaccines.

PMID- 16100696
TI  - European Society for Impotence Research--third meeting. 30 January-2 February
      2000, Barcelona, Spain.
AB  - The role of sildenafil (Viagra; Pfizer Inc) in a variety of indications,
      including spinal cord injury following prostatectomy, was presented. Results
      obtained by comparing different therapies were also presented. The role of
      sildenafil in long-term users of intracavernous and intra-urethral therapy was
      presented by at least two groups with interesting results. Conversely, a
      presentation on the role of intracavernosal therapy in patients who had failed to
      respond to sildenafil revealed thought provoking-findings. The anticipation by
      delegates of an opportunity to preview new therapy was also satisfied, at least
      in part, with presentations on Invicorp (Senetek plc), sublingual apomorphine
      (TAP Pharmaceuticals Inc), BAY-38-9456 (Bayer Yakuhin Ltd), and a
      yohimbine/arginine combination. MUSE therapy (VIVUS Inc) was also revisited. The
      various presentations on the treatment of erectile dysfunction revealed a trend
      towards a more practical approach.

PMID- 16100698
TI  - Anti-epileptic drugs: newly licensed and under development.
AB  - Approximately 1% of the world population (50 million people) suffers from
      epilepsy. Although the long-established anti-epileptic drugs allow 80% of newly
      diagnosed patients to remain seizure-free, many patients experience intolerable
      side effects the remaining 20% of patients do not respond to these drugs. There
      has therefore been a need for new anti-epileptic drugs, and the past decade has
      seen the licensing of eight new drugs worldwide, although these drugs have made
      little impact on the prognosis of refractory epilepsy. Furthermore, the side
      effect profiles of these new drugs do not differ significantly from the
      established antiepileptic drugs, so new anti-epileptic drugs with novel
      therapeutic targets, enhanced efficacy and minimal side effects are needed.

PMID- 16100699
TI  - Leukotriene receptor antagonists for the treatment of asthma.
AB  - Leukotriene receptor antagonists (LTRAs) are novel medications that provide
      symptom control in patients with persistent asthma. Current guidelines recommend
      the use of LTRAs as a treatment option for patients with mild-persistent asthma
      of at least 12 years of age. As illustrated by the results of controlled,
      multicenter clinical trials with zafirlukast and montelukast, as well as studies
      with pranlukast in Japan, LTRAs reduce daytime and night time asthma symptoms,
      improve pulmonary function, lower beta-adrenergic agonist use, and reduce asthma
      morbidity in patients with mild-intermittent to moderate-persistent asthma.
      Moreover, several recent clinical studies demonstrate that these agents are
      effective in preventing exercise-induced bronchoconstriction in children, and in
      improving disease control in symptomatic patients taking inhaled steroids. Based
      on clinical results to date, LTRAs appear to be safe and well tolerated in
      patients with mildto- moderate asthma. These agents represent an important
      addition to the drug armamentarium against asthma.

PMID- 16100700
TI  - Rovelizumab (ICOS Corp).
AB  - Rovelizumab is a humanized monoclonal leukointegrin antibody under development by
      ICOS as a potential treatment for multiple sclerosis (MS), hemorrhagic shock,
      myocardial infarction (MI) and stroke. ICOS announced the commencement of phase
      II studies in MS patients experiencing acute exacerbations in January 1997; a
      randomized, double-blind, placebo-controlled phase III trial for acute ischemic
      stroke, to involve 800 patients, was initiated in January 1999 [312467,313014].
      The compound is also undergoing preclinical investigation for cerebral vasospasm,
      head trauma, kidney transplantation and restenosis [346437]. In September 1999,
      results from a phase II clinical trial in 45 patients suffering from acute
      exacerbations of MS were presented at the Warburg Dillion Read Global Life
      Sciences Conference (New York). The study was designed to evaluate the safety and
      efficacy of four weekly doses of rovelizumab, as compared to placebo. Rovelizumab
      was shown to be safe, but demonstrated no clinical benefit for the recovery of
      neurological functioning [341638]. In February 1997, ICOS announced the
      initiation of a phase II trial in MI. The placebo-controlled trial is being
      coordinated by the Mayo Physician Alliance for Cardiovascular Trials and will
      evaluate safety, pharmacokinetics and infarct size in 60 patients
      [234046,264363]. Patient enrollment for this, and an open label phase II trial in
      trauma-induced hemorrhagic shock, was completed in September 1997 [264363]. An
      expanded shock trial in 150 trauma patients, is expected to complete enrollment
      by the end of 1998 [296831]. An expanded trial for MI was also planned [264363].
      The company is to evaluate rovelizumab in patients with ischemic stroke, and a
      double-blind, dose-escalating, placebo-controlled phase II trial has been
      initiated at several centers in the US [264363]. A patient population of 48 was
      tested, with patient dosing occurring within 12 h of stroke onset symptoms. There
      was no significant difference in SAEs between rovelizumab and placebo treatment,
      and no immunogenicity was observed [315799]. Neuroprotection was observed in a
      rabbit model of focal ischemia, with greatest reduction in infarct noted in the
      cortical areas of the brain. Neutrophil infiltration to ischemic brain parenchyma
      was reduced by 90% [315799]. Rovelizumab is a monoclonal antibody directed
      against the CD11/CD18 cell adhesion proteins. By binding to these receptors,
      rovelizumab prevents the migration and adhesion of neutrophils in the central
      nervous system, which may cause brain inflammation and neuronal loss [167725].
      Rovelizumab binds to all four known leukointegrin receptors, blocking neutrophil
      adhesion and binding to ICAMs [307344]. ICOS collaborated with the University of
      Washington on the preclinical development of this compound [175193].

PMID- 16100701
TI  - Zanamivir (Glaxo Wellcome).
AB  - Zanamivir, a neuraminidase inhibitor under license from Biota, has been developed
      and launched by Glaxo Wellcome for the treatment of influenza virus infection
      [277127]. While registered as drugs, neuraminidase inhibitors are technically
      vaccines as they are believed to work by provoking an immune response, thus
      preventing the spread of infection from one cell to another within the
      respiratory tract [314356]. It is administered, using an inhaler, directly to
      where the virus replicates, minimizing the potential for side effects. Zanamivir
      has been launched, under the name Relenza, for the treatment of influenza in
      Australia [325148], New Zealand [335591] and the UK [341871]. It is registered in
      Mexico and Armenia [346474], and approved in Japan [351580]. In October 1999, it
      was launched in the US [352392] and Glaxo confirmed in January 2000, that
      zanamivir has been launched all over Europe, with the exception of Greece and
      Spain, where launch is imminent [352513]. In October 1999, the British Pharma
      Group (BPG) wrote to the UK Prime Minister to seek a discussion on the
      implications for the British-based pharmaceutical industry of the recommendation
      from NICE's Raised Appraisal Committee that Relenza should be banned from the NHS
      [342597]. An FDA submission was made in October 1998 [302732,304779]; the FDA
      advisory committee met on February 24 1999 to discuss the application [313583].
      The Antivirals Drugs Advisory Committee voted against recommending zanamivir for
      FDA approval [316196]. Members suggested that additional studies using a
      different endpoint or targeting specific high-risk populations would be more
      likely to garner support [317454]. Following a discussion with Glaxo Wellcome in
      April 1999, the FDA indicated that it would continue to review the NDA for
      zanamivir [320565]. In July 1999, the company received final FDA approval for the
      drug for the treatment of both influenza A and B [334127], and aimed to initiate
      a phase IV trial program for the detection of consumer problems with the product,
      following launch of the product in time for the 1999-2000 flu season
      [352392,335048]. In September 1998, Glaxo applied to the Canadian Health
      Protection Branch (HPB) for approval to market zanamivir for the treatment and
      prevention of influenza. A separate application for Fast Track approval was also
      made with the HPB [299375,299472]. In November 1999, zanamivir received approval
      in Canada [346474]. Glaxo expects to make MAA and NDA filings for the use of
      zanamivir as a prophylactic in 1999 [333494]. In July 1998, Merrill Lynch
      predicted that as zanamivir offered only modest benefits gained from a narrow
      treatment window, potential would be limited and forecast annual sales of US
      dollar 30 million [302048]. In January 1999, Paribas predicted sales of pounds 75
      million in 1999, rising to pounds 280 million in 2003 [317650]. In April 1999,
      ABN Amro predicted sales of pounds 23 million in 1999, rising to pounds 326
      million in 2003 [328676]. In August 1999, Lehman Brothers estimated that sales of
      zanamivir will reach US dollar 400 million by 2003, and that it is an obvious
      candidate for an OTC switch, although this is not likely until 5 years after
      launch [336356].

PMID- 16100702
TI  - NS-7 (Nippon Shinyaku).
AB  - Nippon Shinyaku is developing NS-7, a sodium and calcium channel blocker, as a
      neuroprotectant for use following cerebral infarction [249336]. It entered phase
      I trials for the treatment of acute stage cerebrovascular disorders in 1997
      [271963]. As of November 1999, Nippon Shinyaku was preparing to start phase II
      studies in Japan [347972]. In November 1999, Nippon Shinyaku granted Schering
      exclusive developing and marketing rights to NS-7. Schering will conduct clinical
      trials in Europe and the US [347972].

PMID- 16100703
TI  - Neuropathogenesis in cytomegalovirus infection: indication of the mechanisms
      using mouse models.
AB  - Cytomegalovirus (CMV) is the most frequent infectious cause of developmental
      brain disorders and also causes brain damage in immunocompromised individuals.
      Although the brain is one of the main targets of CMV infection, little is known
      about the neuropathogenesis of the brain disorders caused by CMV in humans
      because of the limitations in studying human subjects. Murine CMV (MCMV) is
      similar to human CMV (HCMV) in terms of genome structure, pattern of gene
      expressions, cell tropism and infectious dynamics. In mouse models, it has been
      shown that neural stem/progenitor cells are the most susceptible to CMV infection
      in developing brains. During brain development, lytic infection tends to occur in
      immature glial cells, presumably causing structural disorders of the brain. In
      the prolonged phase of infection, CMV preferentially infects neuronal cells.
      Infection of neurons may tend to become persistent by evasion of immune
      reactions, anti-apoptotic effects and neuron-specific activation of the e1
      promoter, presumably causing functional neuronal disorders. It has also been
      shown that CMV infection in developing brains may become latent in neural
      immature cells. Brain disorders may occur long after infection by reactivation of
      the latent infection.

PMID- 16100704
TI  - Communication and decision-making about seeking inherited cancer risk
      information: findings from female survivor-relative focus groups.
AB  - Dramatic advances in cancer genetics and identification of germline mutations in
      cancer genes such as BRCA1 and BRCA2 have led to new options in genetic risk
      assessment for families with histories of breast and ovarian cancer. However,
      little research has been carried out with individuals and their families
      regarding how cancer risk information is communicated within families and factors
      that may affect individuals and family members making informed decisions about
      their health. This study explored participants' knowledge of cancer risk, their
      perceptions and concerns regarding inherited cancer risk information, family
      communication patterns, and factors that may affect their decision to learn about
      inherited cancer risk in their families. Nine focus groups of family dyads were
      conducted (N=39) consisting of breast or ovarian cancer patients and close female
      relatives. All transcribed interviews were analyzed using qualitative software.
      Key findings showed diversity in how families communicated and made decisions
      about their health, persistent worry for their families, lack of knowledge about
      inherited cancer, vigilance in watching their health, and barriers present in
      communicating about genetic risk. Results from this study support inclusion of
      family members in addressing inherited cancer risk information and contextual
      family factors critical to consider in potentially high risk families.

PMID- 16100705
TI  - Physical activity among breast cancer survivors: regular exercisers vs
      participants in a physical activity intervention.
AB  - BACKGROUND: Secondary prevention is of great importance in the cancer survivor
      population, given the substantial medical risks survivors face. Consequently,
      researchers have begun developing interventions that target behavioral risk
      factors, such as sedentary lifestyle, among survivors. This study represents a
      novel approach for evaluating the efficacy of a physical activity intervention
      for breast cancer survivors. METHODS: Repeated measures analyses were used to
      compare a group of previously sedentary breast cancer survivors offered a
      physical activity intervention (n=43) with a group of regularly active survivors
      (n=40). These two groups were compared on select behavioral and psychosocial
      measures associated with physical activity. RESULTS: Results indicated
      significant time x group effects on the following: behavioral processes of
      change, minutes of moderate-intensity activity/week, and time to complete the one
      mile walk test (a measure of fitness). There was also a borderline significant
      interaction for self-efficacy. Contrasts indicated that, for each interaction,
      previously sedentary and regularly active survivors differed at baseline, but
      were not significantly different postintervention. CONCLUSIONS: Thus, after
      completing a 12-week physical activity intervention, previously sedentary breast
      cancer survivors became similar to regularly active survivors on select
      behavioral and psychosocial measures associated with physical activity.

PMID- 16100706
TI  - Differing strategies of patterning of follicular cells in higher and lower
      brachycerans (Diptera: Brachycera).
AB  - In all higher dipterans (Brachycera), including the fruitfly, Drosophila
      melanogaster, each egg chamber (ovarian follicle) consists of a group (clone) of
      germ cells (one oocyte and 15 accompanying nurse cells) that is surrounded by a
      layer of somatic mesodermal follicular cells (FCs). As oogenesis progresses the
      initially uniform FCs diversify into several morphologically and functionally
      distinct subpopulations. In D. melanogaster some of these subpopulations, e.g.,
      border, centripetal, and dorsolateral cells, undertake coordinated migration or
      rearrangement over the surface of the germ cells. During the final stages of
      oogenesis these subpopulations participate in the formation of a complex,
      regionally specialized eggshell. In representatives of lower brachycerans
      (Orthorrhapha), only FCs that undertake active, directed migration are the border
      cells. These cells originate at the anterior pole of the ovarian follicle and
      migrate between the nurse cells to the anterior pole of the oocyte. Reduced
      motility of FCs in lower brachycerans results in the absence of certain FC
      subpopulations in their egg chambers and subsequent simplicity of their
      eggshells. We found that the lack of some FC subpopulations coincided with the
      appearance of lamellipodium-like protrusions of the oocyte. These protrusions
      penetrated between the apposing membranes of nurse and FCs and partially
      enveloped the nurse cell compartment. Analysis of whole-mount preparations
      stained with rhodamine-conjugated phalloidin revealed that the protrusions
      contained microfilaments and that their tips were equipped with actin-rich
      filopodium-like processes. We also found that in some lower brachycerans
      (representatives of the family Rhagionidae), the FCs located at the posterior
      pole of the oocyte, became enlarged and morphologically similar to the anterior
      border cells. These findings indicate that in higher dipterans the processes
      leading to the formation of a functional egg are variable and often markedly
      different from those in the model organism, D. melanogaster.

PMID- 16100707
TI  - Generation of a conditionally null allele of the laminin alpha1 gene.
AB  - Laminins are heterotrimeric glycoproteins of the basement membranes. Laminin 1
      (alpha1, beta1, gamma1) is the major laminin expressed during early mouse
      embryogenesis. To gain access to the physiological function of laminin alpha1
      chain, we developed a conditionally null allele of its encoding gene (Lama1)
      using the cre/loxP system. Floxed-allele-carrying mice (Lama1(flox/flox)) display
      no overt phenotype. Lama1(flox/flox) mice were crossed with transgenic deleter
      mice (CMV-Cre) to generate Lama1-deficient mice (Lama1(Delta/Delta)).
      Lama1(Delta/Delta) embryos die during the early postimplantation period after
      embryonic day 6.5. They lack Reichert's membrane, an extraembryonic basement
      membrane in which laminin alpha1 is normally highly expressed. In parallel,
      Lama1(Delta/Delta) embryos display 1) parietal and visceral endoderm
      differentiation defects with altered expression of cytokeratin 19 and GATA4,
      respectively, and 2) an induction of apoptosis. This new mouse model is of
      particular interest as it will allow time- and tissue-specific inactivation of
      the Lama1 gene in various organs.

PMID- 16100708
TI  - Differences in patterns of depression after treatment for breast cancer.
AB  - Depression is a significant problem for some breast cancer survivors after the
      end of treatment. This study assessed depression using the CES-D for 84 breast
      cancer patients at the conclusion of radiation treatment, and at 3 and 6 months
      post-treatment. Based on the pattern of CES-D scores, patients were divided into
      five groups: (1) Stay Depressed (scores above clinical cutoff for depression at
      all timepoints); (2) Recover (above threshold at baseline, but below at follow
      up); (3) Become Depressed (below threshold at baseline, but above at follow-up);
      (4) Never Depressed (below threshold at all times); and (5) Vacillate (none of
      the above patterns). This study examined the relationships between depression
      groups and a variety of medical, demographic, and psychological measures,
      including anxiety and quality of life (QOL). Number of children at home
      significantly distinguished the groups, with the Become Depressed group having
      more children and the Vacillate group having fewer children. Anxiety levels were
      different among the groups, with Recover and Never Depressed groups having
      consistently lower anxiety scores. QOL scores also distinguished the groups in
      that Never Depressed patients demonstrated better QOL than all other groups. The
      findings have implications for understanding resilience in cancer patients.

PMID- 16100709
TI  - Morphological evidence of sensory neurons in the root of the rat tongue.
AB  - In our previous studies, a large number of substance P (SP)-immunoreactive (IR)
      nerve fibers were detected in the rat tongue and their number increased after
      inflammation, suggesting that these fibers might be involved in the axon reflex.
      Therefore, in this study, we have examined the different neuropeptide-containing
      nerve elements by light, electron, and confocal laser microscopy. SP, vasoactive
      intestinal polypeptide (VIP), and neuropeptide Y (NPY) IR varicose fibers were
      numerous compared with other ones. Small groups of ganglia with perikarya IR for
      SP, VIP, NPY, galanin, and somatostatin were observed. The SP-IR nerve cell
      bodies were mainly located in the tunica propria just below the epithelial
      lining. Double-labeling immunohistochemistry showed that the intrinsic SP-IR
      neurons did not colocalize VIP. The SP containing nerve terminals were observed
      in and below the epithelium as well as in very close contact to or making real
      synapses with other neurons in the intralingual ganglion. Our data confirmed the
      possibility of intrinsic sensory neurons, which might be the afferent branch of
      the intralingual reflex arch, while the VIP- and NPY-IR neurons located in the
      salivary glands, around the blood vessels, and in the muscle layer might
      constitute the efferent site of this reflex.

PMID- 16100710
TI  - Specialization in pyramidal cell structure in the sensory-motor cortex of the
      Chacma baboon (Papio ursinus) with comparative notes on macaque and vervet
      monkeys.
AB  - The systematic study of pyramidal cell structure has revealed new insights into
      specialization of the phenotype in the primate cerebral cortex. Regional
      specialization in the neuronal phenotype may influence patterns of connectivity
      and the computational abilities of the circuits they compose. The comparative
      study of pyramidal cells in homologous cortical areas is beginning to yield data
      on the evolution and development of such specialized circuitry in the primate
      cerebral cortex. Recently, we have focused our efforts on sensory-motor cortex.
      Based on our intracellular injection methodology, we have demonstrated a
      progressive increase in the size of, the branching structure in, and the spine
      density of the basal dendritic trees of pyramidal cells through somatosensory
      areas 3b, 1, 2, 5, and 7 in the macaque and vervet monkeys. In addition, we have
      shown that pyramidal cells in premotor area 6 are larger, more branched, and more
      spinous than those in the primary motor cortex (MI or area 4) in the macaque
      monkey, vervet monkey, and baboon. Here we expand the basis for comparison by
      studying the basal dendritic trees of layer III pyramidal cells in these same
      sensory-motor areas in the chacma baboon. The baboon was selected because it has
      a larger cerebral cortex than either the macaque or vervet monkeys; motor cortex
      has expanded disproportionately in these three species; and motor cortex in the
      baboon reportedly has differentiated to include a new cortical area not present
      in either the macaque or vervet monkeys. We found, as in monkeys, a progressive
      increase in the morphological complexity of pyramidal cells through areas 3b, 5,
      and 7, as well as from area 4 to area 6, suggesting that areal specialization in
      microcircuitry was likely to be present in a common ancestor of primates. In
      addition, we found subtle differences in the extent of the interareal differences
      in pyramidal cell structure between homologous cortical areas in the three
      species.

PMID- 16100711
TI  - Noninvasive visualization of molecular events in the mammalian zygote.
AB  - Following fertilization, a number of molecular events are triggered in the
      mammalian zygote. As biochemical studies using mammalian gametes and zygotes have
      inherent difficulties, the molecular nature of these processes is currently
      unclear. We have developed a method to visualize these events. In vitro
      transcribed mRNAs encoding for proteins fused with green fluorescent protein were
      microinjected into oocytes or embryos and fluorescence signals were observed.
      Using this technique we succeeded in obtaining images of the DNA methylation
      status in living mouse and rabbit embryos. Moreover, time-lapse images were
      acquired of spindle and nuclear formation during second meiosis and first
      mitosis. Importantly, the microinjected embryos developed to the normal offspring
      even after observation, suggesting that the technique is relatively noninvasive.
      Thus, our method may help elucidate the molecular aspects of fertilization and
      preimplantation development and, based on the real-time genetic and epigenetic
      status, could become a tool to select "good quality" embryos before implantation.

PMID- 16100713
TI  - Monitoring reproducibility of single analysis, single platform CD4 cell counts in
      a high volume, low resource laboratory setting using sequential bead count rates.

PMID- 16100712
TI  - Mutation finding in patients with dysferlin deficiency and role of the dysferlin
      interacting proteins annexin A1 and A2 in muscular dystrophies.
AB  - Mutations in the DYSF gene underlie two main muscle diseases: Limb Girdle
      Muscular Dystrophy (LGMD) 2B and Miyoshi myopathy (MM). Dysferlin is involved in
      muscle membrane-repair and is thought to interact with other dysferlin molecules
      and annexins A1 and A2 at the sarcolemma. We performed genotype/phenotype
      correlations in a large cohort of dysferlinopathic patients and explored the
      possible role of annexins as modifier factors in LGMD-2B and MM. In particular,
      clinical examination, expression of sarcolemmal proteins and genetic analysis
      were performed on 27 dysferlinopathic subjects. Expression of A1 and A2 annexins
      was investigated in LGMD-2B/MM subjects and in patients with other muscle
      disorders. We identified 24 different DYSF mutations, 10 of them being novel. We
      observed no clear correlation between mutation type and clinical phenotype, but
      MM patients were found to display muscle symptoms significantly earlier in life
      than LGMD subjects. Remarkably, dysferlinopathic patients and subjects suffering
      from other muscular disorders expressed higher levels of both annexins compared
      to controls; a significant correlation was observed between annexin expression
      levels and clinical severity scores. Also, annexin amounts paralleled the degree
      of muscle histopathologic changes. In conclusion, our data indicate that the
      pathogenesis of different inherited and acquired muscle disorders involves
      annexin overexpression, probably because these proteins actively participate in
      the plasmalemma repair process. The positive correlation between annexin A1 and
      A2 and clinical severity, as well as muscle histopathology, suggests that their
      level may be a prognostic indicator of disease.

PMID- 16100714
TI  - SCAI, GE healthcare congratulate 2005 awardees, encourage applications for 2006
      SCAI/GE Healthcare Fellows Grant Program.

PMID- 16100715
TI  - The 2005 National Meeting at Ponte Vedra: a great meeting and a very good sign
      for the future.

PMID- 16100716
TI  - Determination of enantiomeric composition by negative-ion electrospray ionization
      mass spectrometry using deprotonated N-(3,5-dinitrobenzoyl)amino acids as chiral
      selectors.
AB  - The ability to use mixtures of deprotonated N-(3,5-dinitrobenzoyl)amino acids as
      chiral selectors for the determination of enantiomeric composition by
      electrospray ionization-mass spectrometry is demonstrated. For each experiment,
      two N-(3,5-dinitrobenzoyl)amino acids were chosen such that each would have
      opposite selectivity for the enantiomers of the analyte. Electrospray ionization
      mass spectrometry, monitored in the negative ion mode, of solutions containing
      the two N-(3,5-dinitrobenzoyl)amino acids, sodium hydroxide, and the analyte, in
      a one-to-one mixture of methanol and water, afford peaks in the mass spectrum
      that correspond to the deprotonated 1:1 analyte-selector complexes. The ratio of
      the intensities of the complexes in the mass spectrum can be related to the
      enantiomeric composition of the analyte. Additionally, the sense and extent of
      chiral recognition is consistent with chromatographic observations, using chiral
      stationary phases derived from N-(3,5-dinitrobenzoyl)amino acids. Each analysis
      of enantiomeric composition requires less than 10 s to complete, indicating that
      this method has great potential for the development of fast-/high-throughput
      chiral analyses.

PMID- 16100717
TI  - Thermally induced coil-to-helix transition of sodium gellan gum with different
      molar masses in aqueous salt solutions.
AB  - Using 5 samples of well-purified Na-gellans (Na-gellans G1-G5, weight-average
      molar mass M(w) = 120 x 10(3)-32 x 10(3) at 40 degrees C), the effects of molar
      mass on the coil-to-double-helix transition in aqueous solutions with 25 mM NaCl
      were studied by light scattering and circular dichroism (CD) measurements,
      viscometry, and differential scanning calorimetry (DSC). From the temperature
      dependence of M(w), molar ellipticity at 201 nm [theta]201, intrinsic viscosity
      [eta], and DSC exothermic curves, it was found that the coil-to-double-helix
      transitions for G1-G5 samples took place at almost the same temperature. The
      [eta] and M(w) obtained in the temperature range from 40 to 25 degrees C can be
      explained by a simple coil/double-helix equilibrium model using the double-helix
      contents determined from CD data. The van't Hoff's transition enthalpy deltaH(vH)
      of Na-gellans depended on M(w). It is concluded that the coil-to-double-helix
      transitions of Na-gellans are all-or-none type transitions, and are accelerated
      with increasing M(w).

PMID- 16100718
TI  - Compressibility changes accompanying conformational transitions of apomyoglobin.
AB  - We used high-precision density and ultrasonic velocity measurements to
      characterize the native (N), molten globule (MG), and unfolded (U) conformations
      of apomyoglobin. The molten globule states that were studied in this work include
      the MG(pH4)(NaCl) state observed at pH 4 and 20 mM NaCl, the MG(pH4)(NaTCA) state
      observed at pH 4 and 20 mM sodium trichloracetate (NaTCA), the MG(pH2)(NaCl)
      state observed at pH 2 and 200 mM NaCl, and the MG(pH2)(NaTCA) state observed at
      pH 2 and 20 mM NaTCA. We used our densimetric and acoustic data to evaluate
      changes in adiabatic compressibility associated with the acid- or salt-induced N
      to-MG, MG-to-U, MG-to-MG, and U-to-MG transitions of the protein. The N-to
      MG(pH4)(NaCl) and N-to-MG(pH4)(NaTCA) transitions are accompanied by decreases in
      compressibility of -(3.0 +/- 0.6) x 10(-6) and -(2.0 +/- 0.6) x 10(-6) cm3 g(
      1)bar(-1), respectively. The N-to-MG(pH2)(NaCl) and N-to-MG(pH2)(NaTCA)
      transitions are associated with compressibility changes of -(4.9 +/- 1.1) x 10(
      6) and (0.7 +/- 0.9) x 10(-6) cm3 g(-1) bar(-1), respectively. We interpret these
      data in terms of the degree of unfolding of the various molten globule forms of
      apomyoglobin. In general, our compressibility data reveal significant disparities
      between the various equilibrium molten globule states of apomyoglobin while also
      quantitatively characterizing each of these states. Volumetric insights provided
      by our data facilitate gaining a better understanding of the folding pathways,
      intermediates, and kinetics of apomyoglobin folding.

PMID- 16100719
TI  - Physical characterization of different-roughness titanium surfaces, with and
      without hydroxyapatite coating, and their effect on human osteoblast-like cells.
AB  - The aim of this study was to characterize and compare various titanium (Ti) and
      hydroxyapatite (HA) coatings on Ti6Al4V, in view of their application on
      noncemented orthopedic implants. Two innovative vacuum plasma sprayed (VPS)
      coatings, the first of ultrahigh rough and dense Ti (PG60, Ra=74 microm) and the
      second of ultrahigh rough and dense Ti coated with HA (HPG60, Ra=52 microm), have
      been developed, and the response of osteoblast-like cells (MG-63) seeded on these
      new coatings was evaluated in comparison to: a low roughness and sandblasted
      (Ti/SA, Ra=4 microm) Ti6Al4V surface; Ti medium (TI01, Ra=18 microm), and high
      (TI60, Ra=40 microm) roughness VPS coatings; and the relative Ti plus HA duplex
      coatings (HT01, Ra=12 microm and HT60, Ra=36 microm respectively), also obtained
      by VPS. PG60 coating presented no open porosity, making it dense and potentially
      intrinsically stronger. Cell adhesion and proliferation on PG60 was similar to
      those of the smoothest one (Ti/SA) and adhesion on ultrahigh roughness was lower
      than the medium- and high-roughness coatings, whereas cell proliferation on PG60
      was lower than TI60. The HA coating determined significant increases in cell
      proliferation at medium and high roughness levels when compared to the relative
      Ti coating, but not compared to the ultrahigh one; all HA-coated surfaces showed
      a decrease in alkaline phosphatase activity and collagen I production. Surface
      morphology and the HA coating strongly affected cell behavior. However, ultrahigh
      values of roughness are not correctly seen by cells, and the presence of HA has
      no improving effects.

PMID- 16100721
TI  - Abstracts of the Pediatric Interventional Cardiac Symposium and Emerging New
      Technologies in Congenital Heart Surgery (PICS/ENTICHS-2005) and the World
      Congress of Pediatric Cardiology and Cardiac Surgery. September 2005, Buenos
      Aires, Argentina.

PMID- 16100722
TI  - Endoluminal hydrogel films made of alginate and polyethylene glycol: physical
      characteristics and drug-eluting properties.
AB  - Drug-eluting stents signify a major achievement in reducing the incidence of
      coronary restenosis after percutaneous transluminal coronary angioplasty.
      However, where drug-eluting stents have been unsuccessful, endoluminal gel-paving
      strategies offer renewed optimism, mainly in a variety of vascular procedures
      requiring catheter-based sustained, localized delivery of therapeutic drugs, and
      biological factors. Despite promising results in animals, endoluminal paving has
      met with very limited clinical success because of the technical difficulties and
      stringent safety demands. The current study presents an alternative to gel paving
      using 40-mum-thick biodegradable polymeric films for deployment onto the artery
      wall during balloon angioplasty and stenting. The films are made from a durable
      yet compliant network of alginate and polyethylene glycol (PEG), and are securely
      held affixed to the vessel wall by the expanded stent struts. The alginate-based
      films are characterized by measuring their strength, elasticity, degree of
      swelling, degradability in water and saline, and drug release properties. The
      combination of alginate and PEG afforded the films sufficient strength and
      compliance for endoluminal deployment using an in vitro organ culture system. In
      characterizing the film degradability, it was discovered that the ionic
      concentration of the buffered saline was the main determinant in regulating the
      degradation kinetics and the release kinetics of the drug molecule Paclitaxel.
      These results suggest that the use of alginate-based, PEG-containing polymeric
      films for endoluminal coverage offers an alternative solution to conventional
      drug-eluting stents, with the added advantage of uniform endoluminal coverage of
      the treated segment and homogeneous endoluminal application of the active
      substance.

PMID- 16100723
TI  - Bifurcation of the femur with tibial agenesis and additional anomalies.
AB  - Bifurcation of the femur and tibial agenesis are rare anomalies and have been
      described in both the Gollop-Wolfgang Complex and the tibial agenesis
      ectrodactyly syndrome. We report on two patients with bifurcation of the femur
      and tibial agenesis. Hand ectrodactyly was seen in one of these patients. Both
      patients had unusual additional anomalies. The first patient had in addition
      proximal focal femoral deficiency, the other patient had a tracheo-esophageal
      fistula and pyloric stenosis. Clinical and genetic aspects are discussed.

PMID- 16100724
TI  - Non-skewed X-inactivation may cause mental retardation in a female carrier of X
      linked alpha-thalassemia/mental retardation syndrome (ATR-X): X-inactivation
      study of nine female carriers of ATR-X.
AB  - X-linked alpha-thalassemia/mental retardation syndrome (ATR-X) is a syndromic
      form of X-linked mental retardation. We investigated the X-inactivation status of
      nine female ATR-X carriers by methylation-specific PCR of the HUMARA gene. Six
      carriers demonstrated a skewed X-inactivation pattern (>90:10) and one showed a
      non-skewed pattern (72:28), while two were uninformative because of homozygosity
      for the CAG repeat polymorphic alleles in the HUMARA. Only the carrier mother who
      showed non-skewed X-inactivation had moderate mental retardation. These findings
      suggest that mutations in ATRX may cause mental retardation in females, if the X
      chromosome carrying mutated ATRX is not properly inactivated.

PMID- 16100725
TI  - Risks of human conotruncal heart defects associated with 32 single nucleotide
      polymorphisms of selected cardiovascular disease-related genes.
AB  - Investigating possible genetic polymorphisms and gene-environment interactions in
      the etiology of human conotruncal defects is a prudent research approach. In this
      study we explore gene-only and gene-environment effects of 32 single nucleotide
      polymorphisms (SNPs) on conotruncal defect risks. The genes bearing these SNPs
      participate in one of five pathogenetic processes, homocysteine metabolism,
      coagulation, cell-cell interaction, inflammatory response, and blood pressure
      regulation. We used DNA samples and data from a California population-based case
      control interview study (1987-1988 birth cohort). We employed a multilocus allele
      specific hybridization assay. Allelic variants were determined by genotyping 155
      infants with conotruncal defects (cases) and 437 infants without malformations
      (controls). Among the 32 SNPs, four were associated with odds ratios of 2 or
      more, and two with odds ratios of 0.5 or less. The four SNPs were F2 G20210A
      (prothrombin) with an odds ratio of 2.5 (95% confidence interval; 0.9-7.0), F7
      promoter (-323) 10-bp del/ins with an odds ratio of 2.3 (0.8-6.8), ITGB3 leu33pro
      (platelet glycoprotein IIIa) with an odds ratio of 2.2 (0.9-5.7), and NPPA T2238C
      (atrial natriuretic precursor peptide) with an odds ratio of 2.9 (0.8-10.1). Two
      SNPs were associated with decreased risks: TNF (tumor necrosis factor, G (-376A))
      and ADD1 gly460trp (alpha adducin) with odds ratios of 0.5 (0.1-2.3) and 0.5 (0.2
      1.9), respectively. Analyses that investigated a potential gene-nutrient
      interaction between maternal periconceptional vitamin use and MTHFR genotypes did
      not indicate that the CT or TT genotype contributed to conotruncal defect risk in
      infants even in the absence of maternal use of multivitamin supplements with
      folic acid. Analyses that investigated a potential interaction on risk between
      NOS3 genes and maternal cigarette smoking, revealed some evidence for higher risk
      of conotruncal defects in infants whose mothers smoked cigarettes
      periconceptionally and who had one of the variant alleles for NOS3 A(-922G) or
      NOS3 glu298asp compared to those infants whose mothers did not smoke and whose
      genotypes were wild-type. Our results provide some support for involvement of
      genetic variation of biologically relevant candidate genes for some birth defects
      whose pathogenesis may be related to altered vascular tone or integrity. In
      particular, NPPA appears to be a good candidate gene for conotruncal defects and
      warrants further investigation.

PMID- 16100726
TI  - Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome.
AB  - The Cornelia de Lange syndrome (CdLS) (OMIM# 122470) is a dominantly inherited
      multisystem developmental disorder. The phenotype consists of characteristic
      facial features, hirsutism, abnormalities of the upper extremities ranging from
      subtle changes in the phalanges and metacarpal bones to oligodactyly and
      phocomelia, gastroesophageal dysfunction, growth retardation, and
      neurodevelopmental delay. Prevalence is estimated to be as high as 1 in 10,000.
      Recently, mutations in NIPBL were identified in sporadic and familial CdLS cases.
      To date, mutations in this gene have been identified in over 45% of individuals
      with CdLS. NIPBL is the human homolog of the Drosophila Nipped-B gene. Although
      its function in mammalian systems has not yet been elucidated, sequence homologs
      of Nipped-B in yeast (Scc2 and Mis4) are required for sister chromatid cohesion
      during mitosis, and a similar role was recently demonstrated for Nipped-B in
      Drosophila. In order to evaluate NIPBL role in sister chromatid cohesion in
      humans, metaphase spreads on 90 probands (40 NIPBL mutation positive and 50 NIPBL
      mutation negative) with CdLS were evaluated for evidence of precocious sister
      chromatid separation (PSCS). We screened 50 metaphases from each proband and
      found evidence of PSCS in 41% (compared to 9% in control samples). These studies
      indicate that NIPBL may play a role in sister chromatid cohesion in humans as has
      been reported for its homologs in Drosophila and yeast.

PMID- 16100727
TI  - Mosaicism of proximal 15q duplication/deletion resulting in Prader-Willi syndrome
      with normal methylation.

PMID- 16100728
TI  - Absent pulmonary valve with intact ventricular septum and patent ductus
      arteriosus: a specific cardiac phenotype associated with deletion 18q syndrome.

PMID- 16100729
TI  - Germline mosaicism of a novel UBE3A mutation in Angelman syndrome.

PMID- 16100733
TI  - Organic azides: an exploding diversity of a unique class of compounds.
AB  - Since the discovery of organic azides by Peter Griess more than 140 years ago,
      numerous syntheses of these energy-rich molecules have been developed. In more
      recent times in particular, completely new perspectives have been developed for
      their use in peptide chemistry, combinatorial chemistry, and heterocyclic
      synthesis. Organic azides have assumed an important position at the interface
      between chemistry, biology, medicine, and materials science. In this Review, the
      fundamental characteristics of azide chemistry and current developments are
      presented. The focus will be placed on cycloadditions (Huisgen reaction), aza
      ylide chemistry, and the synthesis of heterocycles. Further reactions such as the
      aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the
      Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt
      rearrangement, and the Hemetsberger rearrangement bear witness to the versatility
      of modern azide chemistry.

PMID- 16100735
TI  - Ranked set sampling for efficient estimation of a population proportion.
AB  - Ranked set sampling (RSS) is a sampling procedure that can be considerably more
      efficient than simple random sampling (SRS). It involves preliminary ranking of
      the variable of interest to aid in sample selection. Although ranking processes
      for continuous variables that are implemented through either subjective judgement
      or via the use of a concomitant variable have been studied extensively in the
      literature, the use of RSS in the case of a binary variable has not been
      investigated thoroughly. In this paper we propose the use of logistic regression
      to aid in the ranking of a binary variable of interest. We illustrate the
      application of RSS to estimation of a population proportion with an example based
      on the National Health and Nutrition Examination Survey III data set. Our results
      indicate that this use of logistic regression improves the accuracy of the
      preliminary ranking in RSS and leads to substantial gains in precision for
      estimation of a population proportion.

PMID- 16100734
TI  - Familial clustering of beta-cell autoimmunity in initially non-diabetic children.
AB  - BACKGROUND: Type 1 diabetes is characterised by familial aggregation. We set out
      to explore whether beta-cell autoimmunity, which is considered to precede
      clinical disease, also shows familial clustering. METHODS: Tests for HLA DQB1
      alleles (*02, *0301, *0302, *0602) and islet cell autoantibodies (ICA) were
      performed on 5836 children from 2283 families. When a child tested positive for
      ICA, all his/her previous or subsequent samples that were available were also
      tested for insulin autoantibodies (IAA), antibodies to glutamic acid
      decarboxylase (GADA) and antibodies to the IA-2 protein (IA-2A). RESULTS: Forty
      four families were observed to have two or more children positive for at least
      ICA. This proportion (1.9%) was almost five times higher than expected (0.4%; p <
      0.001). The frequency of multiple (>/=2) autoantibodies also showed familial
      aggregation, the observed proportion (0.39%) being three times that expected
      (0.13%; p < 0.001). In 72.7% of the families with at least two ICA-positive
      siblings, the children with autoantibodies had the same HLA DQB1 genotype. The
      median age difference between the ICA-positive children within the same family
      was 3.3 years (range 0.0-10.5 years), and the median time interval in the
      appearance of ICA within the family was 1.6 years (range 0.0-3.2). CONCLUSIONS:
      beta-cell autoimmunity, as defined by the appearance of ICA, demonstrates
      familial aggregation, although the antibodies do not appear in close temporal
      proximity or at an identical age within the same family. The HLA-DQB1 genotypes
      are more often identical in siblings with autoantibodies than in other siblings.

PMID- 16100736
TI  - Utilization of self-sorting processes to generate dynamic combinatorial libraries
      with new network topologies.
AB  - The synthesis of water-soluble, organometallic macrocycles is described. They
      were obtained by self-assembly in reactions of the half-sandwich complexes
      [[Ru(C6H5Me)Cl2]2], [[Ru(p-cymene)Cl2]2], [[Rh(Cp)Cl2]2], and [[Ir(Cp*)Cl2]2]
      with the ligand 5-dimethylaminomethyl-3-hydroxy-2-methyl-4-(1H)-pyridone in
      buffered aqueous solution at pH 8. The structure of the Ru-(p-cymene) complex was
      determined by single-crystal X-ray crystallography. Upon mixing, these complexes
      undergo scrambling reactions to give dynamic combinatorial libraries. In
      combination with structurally related complexes based on amino-methylated 3
      hydroxy-2-(1H)-pyridone ligands, an exchange of metal fragments but no mixing of
      ligands was observed. This self-sorting behavior was used to construct dynamic
      combinatorial libraries of macrocycles, in which two four-component sub-libraries
      are connected by two common building blocks. This type of network topology
      influences the adaptive behavior of the library as demonstrated in selection
      experiments with lithium ions as the target.

PMID- 16100737
TI  - Anion-pi interactions in cyanuric acids: a combined crystallographic and
      computational study.
AB  - Several structures of pi complexes of isocyanuric acid and of several thio
      derivatives with anions have been computed by using high level ab initio
      calculations. The nature of the complexes has been studied by means of the method
      of molecular interaction potential with polarization (MIPp) and Bader's theory of
      atoms-in-molecules. These molecules form favorable complexes with anions and can
      be used as binding units for building receptors for the molecular recognition of
      anions. In several cases, the anion-pi interaction has been demonstrated
      experimentally by means of X-ray crystallography.

PMID- 16100738
TI  - Abstracts of the 21st International Conference on Pharmacepidemiology and
      Therapeutic Risk Management, Nashville, Tennessee, USA, 21-24 August 2005.

PMID- 16100739
TI  - Multivariate adaptive regression splines: a powerful method for detecting disease
      risk relationship differences among subgroups.
AB  - In a wide variety of medical research scenarios one is interested in the question
      whether regression curves differ for subgroups in the sample. Examples are gender
      differences in the effect of drug treatment or the study of genotype-environment
      interactions. To address this question exploratory techniques are often required
      because detailed knowledge concerning the shape of the regression curves and how
      that shape differs across subgroups is lacking. In this article we explored the
      power of two such exploratory techniques: multivariate adaptive regression
      splines (MARS) and least squares curve fitting using polynomials. For this
      purpose simulations were performed using linear, logistic, and complex non-linear
      curves. The power obtained from MARS was on average 1.4 times higher than with
      polynomials. It was shown that power was higher even if the regression curve was
      linear, that gains increased with the complexity of the curve, and that for
      highly non-linear curves model-free methods such as MARS might be the only
      alternative.

PMID- 16100740
TI  - Flow injection chemiluminescence determination of isoniazid using the lucigenin
      periodate system.
AB  - A weak chemiluminescence (CL) signal was observed during the mixing of isoniazid
      with lucigenin in alkaline aqueous solution. The CL signal was enhanced more than
      100 times in the presence of potassium periodate. This CL system was developed
      for the determination of isoniazid using a flow injection mode. The CL intensity
      is proportional to the concentration of isoniazid in the range 0.005-1.0 mg/L.
      The limit of detection is 0.0034 mg/L and the relative standard deviation is 2.0%
      for 0.2 mg/L isoniazid solution in 11 repeated measurements. The method was
      applied to the determination of isoniazid in pharmaceutical preparations and
      satisfactory results were obtained.

PMID- 16100741
TI  - Chemiluminescence during rice seed imbibition at different temperatures.
AB  - The chemiluminescence (CL) of rice (Oryza sativa L.) seeds at different
      temperatures and the CL spectra of rice seed, caryopses and seed coat were
      studied during early imbibition. Compared with the CL of barley (Hordeum vulgare
      L.) and soybean (Glycine max L. Merr.) seeds, the CL of rice seeds had a non
      linear, logarithmic-like increase of intensity in the temperature range 30-50
      degrees C. The Van't Hoff coefficient Q(10) = I(T+10)/I(T) was equal to 2. The
      emission spectrum of whole rice seed, rice and coat had a greater proportion of
      red light during early imbibition, which led to the conclusion that the CL of
      rice seed during early imbibition arises partially from enzyme-catalysed
      reactions.

PMID- 16100742
TI  - Evaluation of several two-dimensional gel electrophoresis techniques in cardiac
      proteomics.
AB  - Two-dimensional gel electrophoresis (2-DE) is currently the best method for
      separating complex mixtures of proteins, and its use is gradually becoming more
      common in cardiac proteome analysis. A number of variations in basic 2-DE have
      emerged, but their usefulness in analyzing cardiac tissue has not been evaluated.
      The purpose of the present study was to systematically evaluate the capabilities
      and limitations of several 2-DE techniques for separating proteins from rat heart
      tissue. Immobilized pH gradient strips of various pH ranges, parameters of
      protein loading and staining, subcellular fractionation, and detection of
      phosphorylated proteins were studied. The results provide guidance for proteome
      analysis of cardiac and other tissues in terms of selection of the isoelectric
      point separating window for cardiac proteins, accurate quantitation of cardiac
      protein abundance, stabilization of technical variation, reduction of sample
      complexity, enrichment of low-abundant proteins, and detection of phosphorylated
      proteins.

PMID- 16100743
TI  - Separation, identification, and interaction of heparin oligosaccharides with
      granulocyte-colony stimulating factor using capillary electrophoresis and mass
      spectrometry.
AB  - A capillary electrophoresis (CE) method was developed for the separation of
      heparin oligosaccharides compatible to study the interactions between the
      oligosaccharides and granulocyte-colony stimulating factor (G-CSF).
      Unfractionated heparin was eliminitively degraded to heparin oligosaccharides by
      an endolytic heparinase. The degraded smaller oligosaccharides (M(r) < 1000) were
      baseline-separated by CE under a 50 mM phosphate buffer (pH 9.0) in 10 min.
      Standard heparin disaccharides and larger oligosaccharides (1000 < M(r) < 8000)
      were all separated under optimized separation conditions. Compared with standard
      heparin disaccharides, smaller oligosaccharides contained one nonsulfated, two
      monosulfated, and two disulfated disaccharides, but trisulfated disaccharides
      were not found. The smaller oligosaccharides were also identified and molecular
      mass was deduced by electrospray ionization-mass spectrometry (ESI-MS).
      Furthermore, interactions between G-CSF and the oligosaccharides were studied by
      using capillary zone electrophoresis (CZE) under the above separation conditions.
      It was found that larger oligosaccharides could interact with G-CSF while smaller
      oligosaccharides were not observed to bind to G-CSF under the experimental
      conditions. In conclusion, the purified heparinase could selectively degrade
      heparin into oligosaccharides and the interaction between G-CSF and heparin was
      correlated with the chain length of heparin.

PMID- 16100744
TI  - Full-capillary sample stacking/sweeping-MEKC for the separation of naphthalene
      2,3-dicarboxaldehyde-derivatized tryptophan and isoleucine.
AB  - In an attempt to improve the sensitivity of detection in capillary
      electrophoresis (CE), a novel online sample-concentration method, full-capillary
      sample stacking (FCSS)/sweeping-micellar electrokinetic chromatography (sweeping
      MEKC) mode, is proposed. Naphthalene-2,3-dicarboxaldehyde (NDA)-derivatized
      tryptophan and isoleucine were selected as model compounds. In the initial step,
      the weakly acidic compounds, dissolved in a low-conductivity buffer (35.1
      microS/cm; apparent ph (pH*) in a mixed solution of acetonitrile/methanol/water,
      4.6), fill the entire capillary, two vials of a high-conductivity buffer (2.06
      mS/cm; pH* 2.0) are placed on each end, and a negative polarity is then applied.
      Under these conditions, the direction of the electroosmotic flow (EOF) is toward
      the inlet. Meanwhile, the anionic analytes move in the reverse direction and are
      neutralized and stacked at the boundary of a dynamic pH-junction (between the
      sample matrix and the nonmicellar background solution (BGS)). When the sample
      concentration is completed, the BGS is quickly changed to solutions containing
      SDS-BGS for the subsequent separation. Since the mobility of SDS-analytes is then
      greater than the EOF, the following steps occur by the sweeping (for focusing)
      and MEKC (for separation) mode. Using these steps, a full-capillary sample
      injection/separation can be achieved.

PMID- 16100745
TI  - Combination of cationic surfactant-assisted solid-phase extraction with field
      amplified sample stacking for highly sensitive analysis of chlorinated acid
      herbicides by capillary zone electrophoresis.
AB  - This report describes a novel online field-amplified sample stacking (FASS)
      procedure to analyze 16 chlorinated acid herbicides. By using a poly(vinyl
      alcohol) (PVA)-coated capillary to reduce electroosmotic flow and introducing a
      methanol-water plug before sample loading, the sample injection time could be
      very long without loss of sample and separation efficiency. Under the optimized
      condition, the FASS procedure could provide great sensitivity enhancement (5000
      10 000-fold) and satisfactory reproducibility (relative standard deviations of
      migration times less than 2.4%, relative standard deviations of peak areas less
      than 8.0%). Combined with cationic surfactant-assisted solid-phase extraction
      (CSA-SPE), the limit of detection of the herbicides ranged from 0.269 to 20.3
      ppt, which are two orders lower than those of the US Environmental Protection
      Agency standard method 515.1. The CSA-SPE-FASS-CE method was successfully applied
      to the analysis of local pond water.

PMID- 16100746
TI  - Two-dimensional gel isoelectric focusing.
AB  - Two-dimensional gel isoelectric focusing (2-D gel IEF) is presented as the
      combination of the same separation method used consecutively in two directions of
      the same gel. In this new method, after completion of IEF process in the first
      dimension the gel was cut into the separate strips, each containing selected
      analytes together with the appropriate part of the original broad pH gradient,
      and the strips were rotated by 90 degrees (with regard to the first IEF) and left
      to diffuse overnight. After diffusion the strips were subjected to the second
      IEF. During the second IEF, the corresponding narrow part of pH gradient in each
      strip was restored again, however, now along the strip. The progress of the
      separation process can be monitored visually by using colored low-molecular
      weight isoelectric point (pI) markers loaded into the gel simultaneously with
      proteins. The unique properties of IEF, focusing and resolution power were
      enhanced by using the same technique twice. Two forms of beta-lactoglobulin (pI
      values 5.14 and 5.31, respectively) non-separated in the first IEF were
      successfully separated in the second dimension at relatively low voltage (330 V)
      with the resolution power comparable to the high-resolution gels requiring the
      high voltage during the run and long separation time. Glucose oxidase loaded as
      diluted solution into ten positions across the gel was finally focused into a
      single band during 2-D gel IEF. Since the first and second IEF are carried out on
      the same gel, no losses and contamination of analyte occur. The suggested method
      can be used for separation/fractionation of complex biological mixtures,
      similarly as other multidimensional separation techniques applied in proteomics,
      and can be followed by further processing, e.g., mass spectrometry analysis. The
      focusing properties of IEF could be useful especially in separation of mixtures,
      where components are at low concentration levels.

PMID- 16100747
TI  - Flow-injection determination of streptomycin residues in milk using the luminol
      periodate-Mn2+ chemiluminescence system.
AB  - A novel flow-injection method with chemiluminescence detection was developed for
      the determination of streptomycin residues in milk, based on the enhancement by
      streptomycin of the luminol-potassium periodate-Mn(2+) chemiluminescence system.
      The assay allowed analysis of streptomycin residues in whole milk samples (
      approximately 3.5% fat) after sample work-up procedures. The limit of detection
      was 5.16 x 10(-9) mol/L for milk, and was far below the regulations of maximum
      residue limits (MRLs). The relative standard deviation (RSD) for 8.66 x 10(-8)
      mol/L streptomycin was 1.94% (n = 15) in milk. The results obtained for the assay
      of streptomycin residues in milk was comparable with those obtained by the
      official methods (ELISA) and demonstrated good accuracy and precision. The
      possible mechanism is briefly discussed.

PMID- 16100748
TI  - Sensitive determination of synephrine by flow-injection chemiluminescence.
AB  - It was found that light emission produced by the oxidation of luminol by
      potassium ferricyanide in basic medium was enhanced by synephrine, an anti
      obesity drug. The optimum conditions for this chemiluminescent reaction were
      studied in detail in a flow injection system and employed in a new, simple and
      rapid method for the determination of synephrine. A mechanism for this reaction
      is proposed, based on the chemiluminescence reaction spectra. In the optimum
      conditions, CL intensity is proportional to concentration of synephrine in the
      0.008-1 microg/mL range. The limit of detection is 1.6 ng/mL for synephrine
      (3sigma), and the relative standard deviation (n = 11) is 2.6% for 0.5 microg/mL
      synephrine. The method was applied to the determination of synephrine in herbal
      products, citrus fruit and biological fluids. The recoveries were satisfactory
      (90-102%). The results given by the proposed method are in good agreement with
      those given by HPLC-UV.

PMID- 16100749
TI  - Simultaneous measurement of superoxide generation and intracellular calcium ion
      of neutrophil-like culture cells.
AB  - We have developed a novel method for simultaneously measuring fluorescence and
      chemiluminescence. The generation of superoxide anion and the intracellular
      Ca(2+) ion concentration of neutrophil-like cells stimulated by agonists were
      measured in real time by our method. Our results were in agreement with the
      intracellular signalling in the neutrophils. We also found that the presence of
      Zn(2+) ion inhibited both the generation of superoxide anion and the influx of
      Ca(2+) ions.

PMID- 16100750
TI  - Detection of botulinum toxins: micromechanical and fluorescence-based sensors.
AB  - Botulinum neurotoxins (BoNTs) are the most lethal of known human toxins, exerting
      their actions by cleaving the soluble N-ethyl maleimide-sensitive fusion protein
      attachment protein receptors (SNAREs) required for neurotransmitter release.
      Early detection of these toxins is important for appropriate medical treatment.
      To detect BoNT activity, traditional assays monitor the effects of the toxins on
      a mammalian organism (observing signs of botulism in mice), or identify cleaved
      substrate molecules (electrophoresis and immunoblot). Similarly, enzyme-linked
      assays were used for screening potential toxin inhibitors in vitro in attempt to
      select antitoxins that could be used for therapeutic purposes. Here we review two
      recently developed sensor systems for detection of toxin activity in vitro and in
      living cells. In vitro detection was carried out using a micromechanosensor that
      relies on the attachment of a bead to the micromachined cantilever through the
      interactions between SNARE proteins, with synaptobrevin 2 deposited onto beads
      and syntaxin 1A deposited onto cantilevers. The presence of toxin is indicated by
      the detachment of the bead, resulting from cleavage of synaptobrevin 2.
      Additional in vitro detection is possible using fluorescent sensors constructed
      by inserting linkers, containing fragments of SNARE proteins acting as toxin
      substrates, between cyan and yellow fluorescent proteins (CFP and YFP). Toxins
      cause the cleavage of these linkers and thereby abolish fluorescence resonance
      energy transfer (FRET) between CFP and YFP. This approach, combined with an
      additional sensor based on subcellular redistribution of YFP fluorescence in
      cells, was used for cell-based screening of toxin activity.

PMID- 16100751
TI  - Is this clinical trial fully registered? A statement from the international
      committee of medical journal editors.

PMID- 16100752
TI  - Review of Croatian genetic heritage as revealed by mitochondrial DNA and Y
      chromosomal lineages.
AB  - The aim of this review is to summarize the existing data collected in high
      resolution phylogenetic studies of mitochondrial DNA and Y chromosome variation
      in mainland and insular Croatian populations. Mitochondrial DNA polymorphisms
      were explored in 721 individuals by sequencing mtDNA HVS-1 region and screening a
      selection of 24 restriction fragment length polymorphisms (RFLPs), diagnostic for
      main Eurasian mtDNA haplogroups. Whereas Y chromosome variation was analyzed in
      451 men by using 19 single nucleotide polymorphism (SNP)/indel and 8 short tandem
      repeat (STR) loci. The phylogeography of mtDNA and Y chromosome variants of
      Croatians can be adequately explained within typical European maternal and
      paternal genetic landscape, with the exception of mtDNA haplogroup F and Y
      chromosomal haplogroup P* which indicate a connection to Asian populations.
      Similar to other European and Near Eastern populations, the most frequent mtDNA
      haplogroups in Croatians were H (41.1%), U5 (10.3%), and J (9.7%). The most
      frequent Y chromosomal haplogroups in Croatians, I-P37 (41.7%) and R1a-SRY1532
      (25%), as well as the observed structuring of Y chromosomal variance reveal a
      clearly evident Slavic component in the paternal gene pool of contemporary
      Croatian men. Even though each population and groups of populations are well
      characterized by maternal and paternal haplogroup distribution, it is important
      to keep in mind that linking phylogeography of various haplogroups with known
      historic and prehistoric scenarios should be cautiously performed.

PMID- 16100753
TI  - HIV legal precedent useful for microbial forensics.
AB  - The field of microbial forensics was formalized because of the need for
      attribution in events where a bioweapon has been used. Microbial forensics has
      its origins in traditional forensics, microbiology, and epidemiology. Microbial
      forensics can be defined as a scientific discipline dedicated to analyzing
      evidence for attribution purposes from a bioterrorism act, biocrime, hoax, or
      inadvertent microorganism/toxin release. This is a very challenging task, since
      there are myriad microorganisms that can pose a threat, and analytical methods
      need to be used reliably. The Scientific Working Group on Microbial Genetics and
      Forensics (SWGMGF) has addressed some quality assurance and control issues, and
      particularly validation criteria (focusing on preliminary validation) due to the
      dynamic nature of evolving investigations. Unique identification of a
      microorganism may never be possible. Yet, qualitative and/or quantitative
      assessments of the evidence can be made. One approach to provide direction on
      gaps in the microbial forensics effort is to perform an end-to-end retrospective
      analysis of past cases. As an example, the case of a gastroenterologist who was
      accused of second degree attempted murder of his paramour using HIV as the weapon
      was reviewed. The scientific evaluation involves epidemiology, molecular biology,
      phylogenetics, and legal deliberations.

PMID- 16100754
TI  - DNA assays for detection, identification, and individualization of select agent
      microorganisms.
AB  - The purpose of this article is to review the status of DNA assays used for the
      detection, identification, and individualization of Bacillus anthracis, Yersinia
      pestis, Francisella tularensis, Burkholderia mallei, and Brucella abortus. These
      select agent microorganisms are historically significant as they have either been
      used or experimented with as a bioweapon or as a terrorist agent and are the
      subject of intense research in the areas of biodefense and bioforensics. If the
      presence of a biological agent is suspected, sensitive and specific assays for
      rapid detection and identification are necessary. However, DNA methods for
      identification of the sample may also be applied in order to individualize the
      strain and potentially determine the source of the microorganism. Methods used at
      the Armed Forces Institute of Pathology (AFIP) for select agent microbial DNA
      analyses include DNA extraction, DNA quantitation, real-time polymerase chain
      reaction (real-time PCR) of genetic targets unique to the select agent
      microorganism, microbial 16S ribosomal RNA gene DNA sequencing, amplified
      fragment length polymorphism polymerase chain reaction (AFLP-PCR), and more
      recently, repetitive element polymerase chain reaction (REP-PCR) DNA
      fingerprinting. The methodologies of 16S ribosomal RNA gene DNA sequencing and
      DNA fingerprinting of microorganisms are well established within the field of
      diagnostic microbiology for DNA identification purposes, as well as DNA typing
      for epidemiological and genetic relatedness studies. 16S ribosomal RNA gene DNA
      sequencing and AFLP DNA fingerprinting have been validated at the Armed Force
      Institute of Pathology (AFIP) laboratory for identification purposes and can be
      used as a possible strain typing tool for Bacillus anthracis, Yersinia pestis,
      Francisella tularensis, as well as Brucella and Burkholderia species. The
      continued development and implementation of new DNA based methods with increased
      sensitivity and defined specificity will be particularly useful for the detection
      of residual microbial DNA signature in situations where the microorganism has
      been rendered nonviable by decontamination procedures or not able to be cultured
      on microbiological media.

PMID- 16100755
TI  - Twelve-year experience in identification of skeletal remains from mass graves.
AB  - AIM: To present twelve-year (1993-2005) experience in identification of human
      remains found in mass graves in Croatia and Bosnia and Herzegovina (BH), as well
      as remains that presumably belonged to Croatian citizens given by Serbia and
      Montenegro. The unique experience of identification of more than a thousand of
      skeletal samples is valuable for better organization of post-mortem
      identifications. METHODS: Standard forensic methods and methods based on DNA
      analysis were used for identification of human remains from mass graves. DNA was
      isolated using standard phenol/chloroform/isoamyl alcohol extraction. In some
      cases, decalcification and repurification were used prior to the extraction to
      overcome inhibition of amplification process. Different DNA systems were used for
      DNA quantitation and amplification (AluQuant, short tandem repeats (STR)
      commercial systems, Y chromosome STRs, and mitochondrial DNA [mtDNA]). Typing of
      PCR products was performed on AmpliType PM and AmpliType DQA1 DNA probe strips,
      ABI PRISM(R) 310 Genetic Analyzer and immobilized sequence-specific
      oligonucleotide (SSO) probes. RESULTS: Up-to-date analysis of 1,155 skeletal
      samples resulted in 703 positively identified bodies: 577 using standard forensic
      methods, 109 by DNA typing, and 17 by combination of these two methods. The
      majority of identifications from 1993 to 1999 was, as usual, achieved by standard
      forensic methods. Later on, these methods were not sufficient and DNA analysis
      was requested. It was performed in 42% of all cases in 12 years. The crucial step
      in DNA analysis is extraction of genomic DNA. Standard phenol/chloroform/isoamyl
      alcohol extraction, complemented with other methods and modifications, proved as
      the most successful method for this step. In certain cases, the quality and/or
      quantity of nDNA was not satisfying and the analysis of the mtDNA was performed.
      CONCLUSION: Our experience demonstrated that the advent of forensic DNA analysis
      methods greatly increased our ability to positively identify previously unknown
      skeletal remains by a comparative genetic analysis with presumptive relatives.

PMID- 16100756
TI  - Challenges of DNA profiling in mass disaster investigations.
AB  - In cases of mass disaster, there is often a need for managing, analyzing, and
      comparing large numbers of biological samples and DNA profiles. This requires the
      use of laboratory information management systems for large-scale sample logging
      and tracking, coupled with bioinformatic tools for DNA database searching
      according to different matching algorithms, and for the evaluation of the
      significance of each match by likelihood ratio calculations. There are many
      different interrelated factors and circumstances involved in each specific mass
      disaster scenario that may challenge the final DNA identification goal, such as:
      the number of victims, the mechanisms of body destruction, the extent of body
      fragmentation, the rate of DNA degradation, the body accessibility for sample
      collection, or the type of DNA reference samples availability. In this paper, we
      examine the different steps of the DNA identification analysis (DNA sampling, DNA
      analysis and technology, DNA database searching, and concordance and kinship
      analysis) reviewing the "lessons learned" and the scientific progress made in
      some mass disaster cases described in the scientific literature. We will put
      special emphasis on the valuable scientific feedback that genetic forensic
      community has received from the collaborative efforts of several public and
      private USA forensic laboratories in assisting with the more critical areas of
      the World Trade Center (WTC) mass fatality of September 11, 2001. The main
      challenges in identifying the victims of the recent South Asian Tsunami disaster,
      which has produced the steepest death count rise in history, will also be
      considered. We also present data from two recent mass fatality cases that
      involved Spanish victims: the Madrid terrorist attack of March 11, 2004, and the
      Yakolev-42 aircraft accident in Trabzon, Turkey, of May 26, 2003.

PMID- 16100757
TI  - Forensic applications of laser capture microdissection: use in DNA-based
      parentage testing and platform validation.
AB  - AIM: To report on the successful use of Laser Capture Microdissection (LCM) as a
      tool for isolation of human chorionic villi from admixed maternal tissue.
      Subsequent DNA isolation for forensic short tandem repeat (STR) analysis for
      parentage testing was performed in two cases of alleged sexual assault of female
      victims. We also performed validation of the LCM instrument platform, using
      archival formalin-fixed human fetal products of conception (POC), for which
      microdissection was utilized to separate maternal (decidua) and fetal (chorionic
      villus) components. METHODS: To isolate DNA from placental chorionic villi
      admixed with maternal decidua recovered after spontaneous or therapeutic
      abortion, LCM was used to separate fetal from maternal cells. In contrast to the
      relatively crude conventional microdissection performed using a narrow pipette,
      needle, or scalpel blade, LCM allows cell- or tissue-specific isolation of
      placental chorionic villi from archival paraffin-embedded tissue sections,
      leaving the maternal tissue intact. RESULTS: After polymerase chain reaction
      (PCR) amplification of villi after LCM of 9-15 STR loci, the quantity and quality
      of DNA yielded from fetal cells isolated by LCM was sufficient for PCR analysis
      and successful forensic parentage testing. The validation data obtained on two
      sets of formalin-fixed archival POC tissues from anonymous donors demonstrated
      the encouraging reproducibility of these protocols and procedures. CONCLUSION: We
      demonstrated the reliability and utility of LCM for forensic applications when
      high specificity of a particular analyzed cell population or tissue is required.
      Care must be taken during routine pathology procedures to avoid contamination of
      tissues with admixture of extraneous DNA.

PMID- 16100758
TI  - Taq polymerase reverses inhibition of quantitative real time polymerase chain
      reaction by humic acid.
AB  - AIM: To investigate the dose-response effect of humic acid (HA) on the
      quantitative real time polymerase chain reaction (QRT-PCR) inhibition and the
      efficiency of Taq polymerase increment in preventing inhibition by HA in DNA
      extracted from ancient bones. METHODS: DNA was isolated from bone samples and DNA
      quantification was conducted with the real-time 5' exonuclease detection assay
      (TaqMan), using the ABI PRISM 7000 instrument. RESULTS: The addition 10-75 ng of
      synthetic HA inhibited QRT-PCR, whereas the addition of 100 ng of synthetic HA
      completely inhibits QRT-PCR. The addition of 1.25 Unit (U) of Taq polymerase per
      assay appeared to be the optimum amount in overcoming the HA inhibition. The best
      results were obtained when crude DNA extracts containing humic substances were
      quantified by QRT-PCR with the addition of 1.25 Unit (U) of extra Taq polymerase
      per assay. CONCLUSION: The modified procedure with increased Taq polymerase
      concentration should allow more effective QRT-PCR analysis in samples containing
      HA.

PMID- 16100759
TI  - Improving efficiency of a small forensic DNA laboratory: validation of robotic
      assays and evaluation of microcapillary array device.
AB  - AIM: To present validation studies performed for the implementation of existing
      and new technologies to increase the efficiency in the forensic DNA Section of
      the Palm Beach County Sheriff's Office (PBSO) Crime Laboratory. METHODS: Using
      federally funded grants, internal support, and an external Process Mapping Team,
      the PBSO collaborated with forensic vendors, universities, and other forensic
      laboratories to enhance DNA testing procedures, including validation of the DNA
      IQ magnetic bead extraction system, robotic DNA extraction using the BioMek2000,
      the ABI7000 Sequence Detection System, and is currently evaluating a micro
      Capillary Array Electrophoresis device. RESULTS: The PBSO successfully validated
      and implemented both manual and automated Promega DNA IQ magnetic bead
      extractions system, which have increased DNA profile results from samples with
      low DNA template concentrations. The Beckman BioMek2000 DNA robotic workstation
      has been validated for blood, tissue, bone, hair, epithelial cells (touch
      evidence), and mixed stains such as semen. There has been a dramatic increase in
      the number of samples tested per case since implementation of the robotic
      extraction protocols. The validation of the ABI7000 real-time quantitative
      polymerase chain reaction (qPCR) technology and the single multiplex short tandem
      repeat (STR) PowerPlex16 BIO amplification system has provided both a time and a
      financial benefit. In addition, the qPCR system allows more accurate DNA
      concentration data and the PowerPlex 16 BIO multiplex generates DNA profiles data
      in half the time when compared to PowerPlex1.1 and PowerPlex2.1 STR systems. The
      PBSO's future efficiency requirements are being addressed through collaboration
      with the University of California at Berkeley and the Virginia Division of
      Forensic Science to validate microcapillary array electrophoresis
      instrumentation. Initial data demonstrated the electrophoresis of 96 samples in
      less than twenty minutes. CONCLUSION: The PBSO demonstrated, through the
      validation of more efficient extraction and quantification technology, an
      increase in the number of evidence samples tested using robotic/DNA IQ magnetic
      bead DNA extraction, a decrease in the number of negative samples amplified due
      to qPCR and implementation of a single multiplex amplification system. In
      addition, initial studies show the microcapillary array electrophoresis device
      (microCAE) evaluation results provide greater sensitivity and faster STR analysis
      output than current platforms.

PMID- 16100760
TI  - Optimization of a simple, automatable extraction method to recover sufficient DNA
      from low copy number DNA samples for generation of short tandem repeat profiles.
AB  - AIM: To develop an automated, high throughput extraction protocol in order to
      produce database eligible profiles from fingerprints and other low copy number
      (LCN) DNA sources. METHODS: Extraction of either purified control DNA or buccal
      cells, for example, with commercial kits was compared to extraction with a simple
      digestion buffer and a subsequent concentration and purification. Results were
      evaluated based on the amount of DNA recovered and the completeness of the DNA
      profiles produced. RESULTS: Simple procedures with fewer steps were superior to
      commercial kits, such as DNA IQ (Promega, Madison, WI, USA) and QiaAmp (Qiagen,
      Valencia, CA, USA), and other protocols with many manipulations. The optimized
      protocol included a thirty-minute incubation with 0.01% SDS and proteinase K at
      56 degrees C, followed by an incubation at 100 degrees C for 10 minutes.
      Concentration of the extract and removal of the SDS was accomplished with a
      Microcon 100 (Millipore, Bedford, MA, USA), which can be assembled into a 96 well
      plate, the Microcon-96 Retentate Assembly Plate (Millipore) for automation. The
      addition of 1 ng Poly A RNA to the Microcon significantly improved DNA recovery.
      CONCLUSION: A one-step sample digestion followed by sample
      concentration/purification minimized sample loss and maximized amplification
      input. Moreover, this methodology can be easily adapted for automation.
      Implementation of this protocol, due to the numerous potential sources of LCN DNA
      samples, will enhance the recovery of biological evidence from crime scenes and
      may be a source of database profiles.

PMID- 16100761
TI  - African Jordanian population genetic database on fifteen short tandem repeat
      genetic loci.
AB  - AIM: To establish a genetic database of the African-Jordanian population for
      forensic and paternity testing purposes. METHOD: Allelic distribution at fifteen
      short tandem repeat (STR) loci was determined for 95 healthy unrelated African
      Jordanians. The 15 autosomal STR loci, included within the GenePrint PowerPlex 16
      system, were amplified from the subset of the 95 DNA extracts isolated from the
      population sample. Electrophoresis for each polymerase chain reaction (PCR)
      product was carried out using the ABI Prism 310 Genetic Analyzer and the length
      of the amplified DNA fragments was determined using the Genotype 2.0 and
      PowerTyper 16 Macro softwares. Calculations of allelic frequencies, forensic
      efficiency parameters, Hardy-Weinberg departure, and quantitative analysis of the
      allele frequencies in various populations were determined. RESULTS: DNA extracts
      were successfully amplified and the genetic database was compiled. All tested
      loci showed no significant statistical deviation from Hardy-Weinberg
      expectations. Furthermore, no significant difference was observed between the
      sample population under investigation and other population genetic databases.
      CONCLUSION: The loci investigated here proved to be sufficiently polymorphic for
      forensic purposes, since the forensic efficiency values suggest that they are
      very discriminating in the African-Jordanian subpopulation.

PMID- 16100762
TI  - Which short tandem repeat polymorphisms are required for identification? Lessons
      from complicated kinship cases.
AB  - This paper presents 5 examples of complicated deficient parentage cases, which
      were sufficiently resolved by extensive DNA typing using short tandem repeat
      (STR) and restriction fragment length polymorphisms (RFLPs). The latter have
      greatly contributed to the solution of deficiency cases, although their
      application is only feasible, if high molecular weight DNA and time are in
      abundance. This apart, RFLP technique is available in a few laboratories only,
      and its extinction can be expected in medium term. This development will pose a
      problem unless more highly polymorphic STR systems are at the service of forensic
      genetic laboratories. The required "new" additional STR polymorphisms must be
      able to fully replace RFLPs in terms of their respective information content. STR
      loci of this quality are e.g. ACTBP2 (SE33), D5S2360, and gonosomal loci.
      Moreover, the newly introduced STR kit "Humantype Chimera" is considered valuable
      from this point of view.

PMID- 16100763
TI  - Forensic DNA identification of animal-derived trace evidence: tools for linking
      victims and suspects.
AB  - AIM: To evaluate the population substructure of purebred dogs and cats in order
      to estimate the true significance of a microsatellite-based DNA match for use as
      evidence in legal proceedings. The high frequency of animal hair as a forensic
      evidence submission necessitates the development of mitochondrial analysis tools
      as well. METHODS: Random samples from a large convenience collection of
      veterinary diagnostic submissions from the western USA were used, as well as
      contributed samples of unrelated purebred cats and dogs. Dogs (n=558) were
      profiled with 17 microsatellites and the data evaluated for Hardy Weinberg and
      linkage equilibrium. The mitochondrial control region (D loop) of dogs (n=348)
      and cats (n=167) was sequenced to determine the haplotype distribution. RESULTS:
      Domestic dogs in the western United States showed significant population
      substructure with marked associations within loci but no disequilibrium between
      loci. A population substructure coefficient Theta=0.11 is recommended for
      calculating genotype frequencies. Mitochondrial haplotypes in cats and dogs show
      less variation than human haplotypes. CONCLUSION: Although population
      substructure occurs in domestic dogs (and can be inferred in cats), the
      discriminatory power of microsatellite analysis is dramatic with even partial DNA
      types, strongly supporting the prosecution of perpetrators in five discussed
      cases. Mitochondrial analysis, while less powerful, adds a layer of evidence in
      four discussed cases.

PMID- 16100764
TI  - Forensic botany: using plant evidence to aid in forensic death investigation.
AB  - Forensic botany is still an under-utilized resource in forensic casework,
      although it has been used on occasion. It is an area of specialty science that
      could include traditional botanical classification of species, DNA, or materials
      evidence (trace and transfer evidence), crime mapping or geo-sourcing, all
      dependent on the specific case application under consideration. Critical to the
      evaluation of plant evidence is careful collection, documentation, and
      preservation for later scientific analysis. This article reviews proper
      procedures and recent cases where botanical evidence played a role in
      establishing either manner or time of death. Plant evidence can be useful for
      determining if a death was due to an accident, suicide, or homicide, or what time
      of year burial may have taken place. In addition, plant evidence can be used to
      determine if a crime scene is a primary or secondary scene and to locate missing
      bodies.

PMID- 16100765
TI  - Risk factors for death and injuries in earthquake: cross-sectional study from
      Afyon, Turkey.
AB  - AIM: To assess the risk factors for deaths and injuries caused by earthquakes in
      a high-risk earthquake zone. METHODS: A cross-sectional study was carried out in
      Eber town, Cay County, following the earthquake of February 3, 2002 in Afyon,
      Turkey. This area was particularly affected by the earthquake, with high number
      of casualties, including many fatalities. The study included 812 persons living
      in Eber at the time of the earthquake. The study population was interviewed at
      their homes to obtain information on the deaths and non-fatal injuries, along
      with potential risk factors for death and injuries. These included the type and
      degree of the damage to the building, precise location and the initial actions of
      victims at the moment of the earthquake, and socio-demographic data. RESULTS:
      Earthquake-related mortality rate was 16 per 1,000 people, injury rate was 22 per
      1,000 people, and death/injury ratio was 1:1.4. During the earthquake, 60% of the
      buildings collapsed or were heavily damaged. Risk factors for death and injury
      were higher among those who lived in collapsed or heavily damaged buildings,
      wooden type buildings, or those who were near the outer walls during the
      earthquake. CONCLUSION: The most important risk factor for earthquake-induced
      mortality and morbidity was the degree of damage to the building. Another
      important risk factor was the location of the individual inside the room at the
      time of the quake.

PMID- 16100766
TI  - Increasing detection of polymerase chain reaction (PCR) by isolation of PCR
      products (IPCRp).
AB  - AIM: To develop a method for enhanced polymerase chain reaction (PCR) product
      detection. METHODS: During the PCR, the double-stranded product is generated with
      fluorescent dye on one strand, and biotin on the other strand. The product is
      captured on the streptavidin-coated plates with high efficiency (IPCRp). Washing
      of the all unamplified compounds, including dye-labeled unincorporated primers,
      follows the PCR. The targeted dye-labeled PCR product is released by denaturation
      and loaded on the detection platform. RESULTS: After the application of the
      IPCRp, the resulting product is highly concentrated targeted dye-labeled single
      stranded DNA, free of the unincorporated primers and other PCR artifacts. The
      strength of the signal of the IPCRp product on detection platform is two- to five
      fold higher than the strength of the signal of the conventional PCR product.
      CONCLUSION: The IPCRp procedure can be accomplished in less than 20 minutes.
      Efficient isolation of the PCR products has two steps, washing and denaturation.
      It can increase the yield of targeted PCR product and increase the sensitivity of
      the detection platform.

PMID- 16100767
TI  - Deregulation of cell growth and malignant transformation.
AB  - Cell growth and cell division are fundamental aspects of cell behavior in all
      organisms. Recent insights from many model organisms have shed light on the
      molecular mechanisms that control cell growth and cell division. A significant
      body of evidence has now been accumulated, showing a direct link between
      deregulation of components of cell cycle machinery and cancer. In addition,
      defects in one or more steps that control growth are important for malignant
      transformation, as many tumor suppressors and proto-oncogenes have been found to
      regulate cell growth. The importance of cell growth in tumor development is
      further supported by the discovery that rapamycin, an effective anticancer drug,
      inhibits a key regulator of protein synthetic machinery and cell growth,
      mammalian target of rapamycin (mTOR). In most cases, cell growth and cell
      division are coupled, thereby maintaining cell size within physiological limits.
      We believe that, in a long-term perspective, understanding how these two
      processes are coordinated in vivo and how their interplay is deregulated in a
      number of diseases, including cancer, may have a direct impact on the efficiency
      of modern therapeutics.

PMID- 16100768
TI  - Association of vitamin D receptor gene polymorphism with susceptibility to
      Graves' disease in Eastern Croatian population: case-control study.
AB  - AIM: To evaluate the effect of vitamin D3 receptor (VDR) gene BsmI/ApaI/TaqI
      restriction fragment length polymorphisms on Graves' disease susceptibility in a
      subset of patients from Eastern Croatia. METHODS: Graves' disease patients
      (n=110) and ethnically matched euthyroid controls (n=99) with no clinical
      evidence or family history of thyroid or autoimmune diseases were genotyped for
      VDR gene polymorphisms by BsmI/ApaI/TaqI endonuclease digestion after polymerase
      chain reaction amplification with sequence-specific primers. Data were analyzed
      by chi-square-test, and crude odds ratios (OR) with 95% confidence interval (95%
      CI) were calculated. RESULTS: The ApaI "AA" (14.5% vs 30.3%, patients vs
      controls, respectively, OR=0.39, 95% CI [0.2-0.77], P=0.01) and BsmI "BB" (7.3%
      vs 23.2%, OR=0.26 [0.11-0.61], P=0.002) genotypes were significantly
      underrepresented in patients, whereas ApaI "aa" (28.2% vs 9.1%, OR=3.92 [1.76
      8.74], P=0.001) and TaqI "TT" (51.8% vs 31.3%, OR=2.36 [1.34-4.16], P=0.004)
      genotypes were significantly more frequent in patients than controls. The
      genotype combination, which conferred the strongest protection against Graves'
      disease, was "BBAAtt" (2.7% vs 17.2%, OR=0.14 [0.04-0.48], P=0.001). CONCLUSION:
      These findings suggest that VDR gene BsmI/ApaI/TaqI polymorphisms are associated
      with Graves' disease susceptibility in a subset of patients from Eastern Croatia.
      The ApaI and BsmI "AA" and "BB" genotypes, respectively, as well as combined
      "BBAAtt" genotype, appeared to confer protection against Graves' disease, whereas
      ApaI "aa" and TaqI "TT" genotypes were associated with an increased risk for
      Graves' disease. However, the true mechanisms of association remain to be
      elucidated.

PMID- 16100769
TI  - Gene expression profile of human Down syndrome leukocytes.
AB  - AIM: Identification of differences in the gene expression patterns of Down
      syndrome and normal leukocytes. METHODS: We constructed the first Down syndrome
      leukocyte serial analysis of gene expression (SAGE) library from a 28 year-old
      patient. This library was analyzed and compared with a normal leukocyte SAGE
      library using the eSAGE software. Reverse transcriptase polymerase chain reaction
      (RT-PCR) was used to validate the results. RESULTS: We found that a large number
      of unidentified transcripts were overexpressed in Down syndrome leukocytes and
      some transcripts coding for growth factors (e.g. interleukin 8, IL-8),
      ribosomaproteins (e.g. L13a, L29, and L37), and transcription factors (e.g., Jun
      B, Jun D, and C/EBP beta) were underexpressed. The SAGE data were successfully
      validated for the genes IL-8, CXCR4, BCL2A1, L13a, L29, L37, and GTF3A using RT
      PCR. CONCLUSION: Our analysis identified significant changes in the expression
      pattern of Down syndrome leukocytes compared with normal ones, including key
      regulators of growth and proliferation, ribosomal proteins, and a large number of
      overexpressed transcripts that were not matched in UniGene clusters and that may
      represent novel genes related to Down syndrome. This study offers a new insight
      into transcriptional changes in Down syndrome leukocytes and indicates candidate
      genes for further investigations into the molecular mechanism of Down syndrome
      pathology.

PMID- 16100770
TI  - Calpainopathy (LGMD2A) in Croatia: molecular and haplotype analysis.
AB  - AIM: To determine types and frequency of CAPN3 mutations in 29 unrelated Croatian
      families, analyzed during 6-year prospective and ongoing genetic and
      epidemiological study of muscular dystrophies in Croatia. METHODS: Mutation
      analysis included allele-specific polymerase chain reaction (PCR) or combination
      of PCR and restriction fragment length polymorphisms (RFLP) methods. Haplotype
      analysis was performed by PCR and DNA electrophoresis using 5 highly polymorphic
      markers flanking CAPN3 gene locus. RESULTS: Mutation analysis revealed the
      presence of 6 different CAPN3 mutations (550delA, R541W, P82L, delFWSAL, R49H,
      Y537X), accounting for 94.8% of CAPN3 chromosomes in the studied population.
      550delA was the most frequent mutation, found in 43/58 (74%) CAPN3 chromosomes,
      whereas the frequency of other five mutations ranged from 2-9%. Haplotype
      analysis of 38 chromosomes carrying 550delA mutation showed the presence of the
      same haplotype on 66% of analyzed chromosomes. CONCLUSIONS: The present data,
      together with our previously published results, explain the frequency and the
      distribution of the 550delA mutation in Croatia by founder effect and genetic
      drift. Results of haplotype study are in favor of the hypothesis that 550delA is
      an old, rather than a recurrent mutation. The findings are important for
      effective diagnostic screening of CAPN3 gene in Croatia and neighboring
      countries, as well as for accurate genetic counseling.

PMID- 16100771
TI  - Gene analysis of steroid 5 alpha-reductase 1 in hyperandrogenic women.
AB  - AIM: To examine the gene encoding for 5alpha-reductase type 1 in hyperandrogenic
      women, and assess the association of its eventual mutations or polymorphisms with
      the development of the hyperandrogenic female pattern. METHODS: Sixteen
      hyperandrogenic women were included in the study. Single-stranded conformation
      polymorphism analysis (SSCP) and DNA sequencing were performed after polymerase
      chain reaction amplification of each of the 5 exons of the SRD5A1 gene in both
      hyperandrogenic and control group (16 participants). RESULTS: Sequence analysis
      identified the existence of many polymorphisms; in codon 24 of exon 1, GGC (Gly)
      into GAC (Asp); in codon 30 of exon 1, CGG (Arg) into CGC (Arg); in exon 3 codon
      169, ACA to ACG (both encoding for threonine); in exon 5, AGA to AGG (both
      encoding for arginine, codon 260); and T/C polymorphism in intron 2.
      Polymorphisms were found in both groups. CONCLUSION: Polymorphisms of SRD5A1 gene
      were the same in both hyperandrogenic and healthy women, indicating no
      significant associations of genetic polymorphisms/variations of SRD5A1 gene with
      clinical manifestations of hyperandrogenic disorders in women.

PMID- 16100772
TI  - Lack of association between genetic markers on chromosome 16q22-Q24 and type 1
      diabetes in Russian affected families.
AB  - AIM: To evaluate whether the T1D susceptibility locus on chromosome 16q
      contributes to the genetic susceptibility to T1D in Russian patients. METHOD:
      Thirteen microsatellite markers, spanning a 47-centimorgan genomic region on
      16q22-q24 were evaluated for linkage to T1D in 98 Russian multiplex families.
      Multipoint logarithm of odds (LOD) ratio (MLS) and nonparametric LOD (NPL) values
      were computed for each marker, using GENEHUNTER 2.1 software. Four
      microsatellites (D16S422, D16S504, D16S3037, and D16S3098) and 6 biallelic
      markers in 2 positional candidate genes, ICSBP1 and NQO1, were additionally
      tested for association with T1D in 114 simplex families, using transmission
      disequilibrium test (TDT). RESULTS: A peak of linkage (MLS=1.35, NPL=0.91) was
      shown for marker D16S750, but this was not significant (P=0.18). The subsequent
      linkage analysis in the subset of 46 multiplex families carrying a common risk
      HLA-DR4 haplotype increased peak MLS and NPL values to 1.77 and 1.22,
      respectively, but showed no significant linkage (P=0.11) to T1D in the 16q22-q24
      genomic region. TDT analysis failed to find significant association between these
      markers and disease, even after the conditioning for the predisposing HLA-DR4
      haplotype. CONCLUSION: Our results did not support the evidence for the
      susceptibility locus to T1D on chromosome 16q22-24 in the Russian family data
      set. The lack of association could reflect genetic heterogeneity of type 1
      diabetes in diverse ethnic groups.

PMID- 16100773
TI  - Expression of p53 and apoptosis in discoid lupus erythematosus.
AB  - AIM: To investigate whether p53 expression and apoptosis play a role in the
      pathogenesis of discoid lupus erythematosus (DLE) and whether they are associated
      with a hyperproliferative state in the epidermis of DLE lesions and epidermal
      atrophy. METHODS: A total of 70 skin biopsy specimens, 35 DLE and 35 normal, were
      used. Expression of protein p53 and Ki-67 was examined immunohistochemically.
      Apoptotic cells were identified by terminal deoxynucleotidyl transferase (TdT)
      mediated nick end labeling (TUNEL). Histopathological examination of hematoxylin
      eosin-stained sections of DLE included analysis and scoring of epidermal atrophy
      and other histopathological parameters. RESULTS: p53 expression was greater in
      DLE than in normal skin (14.5 vs 0.6%, P<0.001). Ki-67 expression was also
      greater in DLE than in normal skin (8.0 vs 3.1%, P<0.001). A significant positive
      correlation between p53 and Ki-67 expression was found in both groups (normal
      skin, r=0.46, P<0.009; DLE, r=0.72, P<0.001). A significant negative correlation
      (r=-0.75, P<0.001) between Ki-67 expression and the intensity of epidermal
      atrophy was found. The degree of apoptosis in the epidermis of DLE lesions with
      higher Ki-67 and p-53 expression was higher than when the expression of these
      molecules was low (3.0+/-1.8 vs 1.6+/-1.5 on a scale from 0-5; P=0.048).
      CONCLUSION: Aberrant p53 expression occurs in the keratinocytes of DLE and is
      associated with keratinocyte hyperproliferation and epidermal atrophy.
      Accumulation of p53 protein, together with an extensive apoptosis, suggests that
      the activation of a p53-induced apoptotic pathway may play a role in the
      pathogenesis of skin lesions in DLE.

PMID- 16100774
TI  - Cytokine gene polymorphisms in population of ethnic Macedonians.
AB  - AIM: To genotype cytokine polymorphisms in the Macedonian population as a part of
      the international project Cytokine Polymorphism Component (CPC). METHODS: The
      sample consisted of 125 healthy unrelated individuals, 46 men and 79 women, aged
      20-35 years. All individuals were of Macedonian origin and nationality, Christian
      Orthodox religion, and residents of different regions of the Republic of
      Macedonia. Blood samples were collected after written consent was obtained, DNA
      was isolated from peripheral blood leukocytes by the phenol-chloroform extraction
      method, and the samples were stored in the Anthropology section of the Macedonian
      Human DNA Bank (hDNAMKD). Fourteen cytokine genes were identified as candidates:
      gamma-interferon (IFNgamma); interleukin (IL) 1 alpha (IL-1alpha); IL-1 beta (IL
      1beta); IL-1 receptor (IL-1R); IL-1R antagonist (IL-1RA); IL-2; IL-4; IL-4
      receptor alpha (IL-4Ralpha); IL-6; IL-10; IL-12B; TGF beta 1 (TGF-beta1); and TNF
      alpha (TNF-alpha). Cytokine genotyping for the anthropology samples was performed
      by polymerase chain reaction with sequence-specific priming (PCR-SSP) (Heidelberg
      kit). The population genetics analysis package, PyPop, was used for the analysis
      of the cytokine data for this report. RESULTS: The frequency of alleles for some
      single nucleotide polymorphisms (SNP) varied from 0.967 for TGF-beta1 cdn25/G and
      0.920 for TNF-alpha -238/G, to 0.914 for IL-1alpha -889/C, indicating common
      "wild type" allele in those cytokines. For the most SNPs, the test of neutrality
      showed negative value for F(nd) statistic, which indicated balancing selection
      operating on the alleles at that locus. F(nd) was negative and significantly
      different from 0 for IFNgamma UTR5644 and TGF-beta1 cdn10 (P=0.006 and P=0.007,
      respectively). Most of SNPs showed a good fit with HWP expectations. A few SNPs
      (IL-1alpha -889, IL-1beta -511, IL-1beta+3962, and IFNgammaUTR5644) were not in
      HWP (P< or =0.005), and Guo and Thompson Hardy Weinberg Output (GTHWO) was
      significant (P< or =0.005). The most frequent haplotypes for TGF-beta1 were TG
      (0.491) and CG (0.476), with the absence of TGF-beta1/TC haplotype in the sample
      from the Macedonian population. Test of neutrality showed negative value for
      F(nd) statistic (Ewens-Watterson test of neutrality) which indicated balancing
      selection operating on the haplotypes at that locus, except for the IL-4
      haplotypes, where it showed a positive value for F(nd) statistic, but without
      significance. F(nd) was negative and significantly different from 0 for IL-10
      haplotypes (P=0.002). In the sample from the Macedonian population, D' was equal
      to 1 in all haplotypes with P values <0.0001, except for TNF-alpha (P< or
      =0.012), which indicated that one or more haplotypes were missing. CONCLUSION:
      The analysis of cytokine alleles, genotypes, and haplotypes in the sample from
      the Macedonian population showed a good fit with Hardy Weinberg equilibrium for
      most of SNPs and can be used for anthropological comparisons, as well as for
      association studies with different diseases.

PMID- 16100775
TI  - Frequency of CCR5 gene 32-basepair deletion in Croatian normal population.
AB  - A 32-basepair deletion polymorphism in the CCR5 chemokine receptor gene (CCR5
      TROKUT 32) could increase the resistance to HIV-1 infection or delayed
      progression to AIDS. This mutant allele is common among Caucasians of Western
      European descent, but has not been observed in people of African or Asian
      ancestry. Genetic studies provided in European countries have shown a highest
      prevalence in Nordic countries and the lowest in the Southern European and
      Mediterranean populations. We genotyped 303 randomly selected healthy Croatians
      for the prevalence of CCR5 TROKUT 32 mutation. CCR5 TROKUT 32 allele frequency in
      Croatia of 7.1% fits in the observed European north/south gradient. This first
      report of CCR5 TROKUT 32 mutation in Croatian population provides additional
      information on its frequency and geographical distribution in Slavic populations
      in South-Eastern Europe. Moreover, our data may have important implications for
      the prediction and prevention of HIV/AIDS in a tourist country such as Croatia.

PMID- 16100776
TI  - Is there a best way to live amidst dilemmas?

PMID- 16100777
TI  - Living on the backs of our grandchildren.

PMID- 16100778
TI  - Africa in the eyes of the world.

PMID- 16100779
TI  - The map-based sequence of the rice genome.
AB  - Rice, one of the world's most important food plants, has important syntenic
      relationships with the other cereal species and is a model plant for the grasses.
      Here we present a map-based, finished quality sequence that covers 95% of the 389
      Mb genome, including virtually all of the euchromatin and two complete
      centromeres. A total of 37,544 non-transposable-element-related protein-coding
      genes were identified, of which 71% had a putative homologue in Arabidopsis. In a
      reciprocal analysis, 90% of the Arabidopsis proteins had a putative homologue in
      the predicted rice proteome. Twenty-nine per cent of the 37,544 predicted genes
      appear in clustered gene families. The number and classes of transposable
      elements found in the rice genome are consistent with the expansion of syntenic
      regions in the maize and sorghum genomes. We find evidence for widespread and
      recurrent gene transfer from the organelles to the nuclear chromosomes. The map
      based sequence has proven useful for the identification of genes underlying
      agronomic traits. The additional single-nucleotide polymorphisms and simple
      sequence repeats identified in our study should accelerate improvements in rice
      production.

PMID- 16100780
TI  - The chemical structure of the Hawaiian mantle plume.
AB  - The Hawaiian-Emperor volcanic island and seamount chain is usually attributed to
      a hot mantle plume, located beneath the Pacific lithosphere, that delivers
      material sourced from deep in the mantle to the surface. The shield volcanoes of
      the Hawaiian islands are distributed in two curvilinear, parallel trends (termed
      'Kea' and 'Loa'), whose rocks are characterized by general geochemical
      differences. This has led to the proposition that Hawaiian volcanoes sample
      compositionally distinct, concentrically zoned, regions of the underlying mantle
      plume. Melt inclusions, or samples of local magma 'frozen' in olivine phenocrysts
      during crystallization, may record complexities of mantle sources, thereby
      providing better insight into the chemical structure of plumes. Here we report
      the discovery of both Kea- and Loa-like major and trace element compositions in
      olivine-hosted melt inclusions in individual, shield-stage Hawaiian volcanoes-
      even within single rock samples. We infer from these data that one mantle source
      component may dominate a single lava flow, but that the two mantle source
      components are consistently represented to some extent in all lavas, regardless
      of the specific geographic location of the volcano. We therefore suggest that the
      Hawaiian mantle plume is unlikely to be compositionally concentrically zoned.
      Instead, the observed chemical variation is probably controlled by the thermal
      structure of the plume.

PMID- 16100781
TI  - The quality assurance programme of the Radiotherapy Group of the European
      Organisation for Research and Treatment of Cancer: past, present and future.
AB  - As early as in 1982, the European Organisation for Research and Treatment of
      Cancer Radiotherapy Group established a quality assurance programme. In the
      course of 20 years, quality assurance procedures have become a vast and important
      part of the activities of the group. Today, the membership committee uses
      standard procedures based on minimal requirements to evaluate current members and
      new membership applications. Moreover, for every new trial, specific quality
      assurance procedures are an integral part of the preparation of the protocol and
      executed under the responsibility of the study coordinator. With the growing
      complexity of the radiotherapy techniques used in the framework of the more
      recent trials, quality assurance procedures have also become more complex
      including trial specific phantom based measurements. Future ways to evaluate all
      steps of the radiotherapy process using a common platform connecting all users
      with the internet are currently under development.

PMID- 16100782
TI  - Cervical cancer prevention in low-resource settings.

PMID- 16100783
TI  - [Renal tumors and pregnancy].
AB  - The article presents a retrospective analysis of literature data on combination
      of renal tumors with pregnancy, three cases are reported. The diagnostic
      algorithm in such patients is based, first of all, on ultrasonography, in
      complicated cases MR imaging is used. Therapeutic policy depends on the tumor
      stage and size, pregnancy term. Urgent radical nephrectomy is recommended in
      trimester I and III. Follow-up with delivery may be employed upon 28 week
      pregnancy in trimester II. Basic therapeutic algorithm of renal angiomyolipoma is
      follow-up. To make a final conclusion on efficacy of therapeutic policy, it is
      necessary to conduct a multicenter prospective trial aimed at assessment of long
      term results of each therapy.

PMID- 16100784
TI  - [Three-dimentional echography in diagnosis and staging of urinary bladder
      cancer].
AB  - The role of USI and three-dimentional volumetric reconstruction was studied in
      diagnosis of urinary bladder cancer diagnosis. 69 UBC patients were examined.
      Examination included renal USI of the kidneys, urinary bladder, prostate,
      echoureterography, cystoscopy, CT, MRT. The number of the tumors, volume, area,
      invasion were studied in 3D mode. US angiography assessed resistance index and
      tumor vascularization by degrees 0-3. USI findings were compared with those of
      MRT, cystoscopy, histomorphology of the biopsies. 2D USI technique proved
      effective in detection of urinary bladder cancer at stage T1 in 66%, 3D in 100.
      At stage T2a-b informative value of both techniques reached 87%. Overall
      informative value of 2D in detection of urinary bladder cancer was 81%, three
      dimentional echography--96%. USI proved effective in diagnosis and staging of
      urinary bladder cancer. Use of 3D ultrasonic angiography facilitates the choice
      of more effective surgical policy in the treatment of urinary bladder cancer
      patients.

PMID- 16100785
TI  - [Sexual dysfunction in males with concomitant urological diseases].
AB  - A clinical data was studied for 117 males without complaints for copulative
      disorders admitted to urological clinic electively for benign prostatic
      hyperplasia (BPH)--44 (37.6%), urolithiasis--25 (21.4%), external genital
      diseases--17 (14.5%), renal cyst and hydronephrosis--16 (13.7%), renal and
      vesical tumors--15 (12.8%). Mean age of the patients was 56.2 +/- 16.1 years. The
      patients filled in IPSS and IIEF questionnaires. Mean score set (+/-SD) for IIEF
      and IPSS was 35 +/- 23 and 12 +/- 10, respectively. The majority of the patients
      (n = 61) were not sexually active. Erectile dysfunction (ED) was detected in 23
      (19.7%) patients: mild and moderate in 19 (16.2%) and 4 (3.4%), respectively). 24
      (73%) patients with normal erectile function, 10 (44%) patients with ED and the
      majority (n = 37) of sexually inactive men were satisfied with their sexual
      activity. Those males who needed improvement of sexual life quality had higher (p
      < 0.05) parameters of erectile function and sexual satisfaction. Age of the
      patients (R2 = 33.1; p < 0.0001) and IPSS index (p < 0.015) were leading indices
      in determining condition of the copulative function. IIEF correlated with tumors
      of the kidney or urinary bladder (p < 0.004) and benign prostatic hyperplasia (p
      < 0.015). Erectile dysfunction in men with urological diseases was closely
      related with age and severity of lower urinary tract symptoms. Other sexual
      disorders may be due both to general causes and urological diseases.

PMID- 16100786
TI  - [Incomplete unilateral intracavernous prosthetic reconstruction in Peyronie's
      disease].

PMID- 16100787
TI  - [Original experience in plastic surgery of pelviureteral segment in
      hydronephrosis in children].
AB  - The study of postoperative urodynamics of the upper urinary tract was made in 339
      patients with obstruction of the pyeloureteral segment and on experimental
      animals (morphological tests). This study revealed factors deteriorating
      functional capacity of anastomosis in early postoperative period. The findings
      allow the surgeons to update the technique of the pyeloureteral segment resection
      and uretero-pyeloanastomosis, to determine indications for applying nonsteroid
      anti-inflammatory drugs in the postoperative period, to reveal advantages and
      establish indications for drainage-free pyeloplasty. Thus, use of drainage-free
      modified technique of pyeloplasty in certain indications is a safe and less
      traumatic method of the patients' management which increases efficacy of Anderson
      Hines operation.

PMID- 16100788
TI  - [A contractile function of various megaureter forms in infants and its
      pharmacological regulation].
AB  - A total of 43 infants under 3 years of age with organic, functional and reflux
      obstructive megaureter were studied. The function of the upper urinary tract was
      examined with dynamic pyeloureterosonography with diuretic load. Contractility of
      isolated fragments of megaureters and possibility of its pharmacological
      regulation were studied in patients after surgery in vitro. Different urodynamic
      variants of the response of refluxing and obstructive megaureters and those with
      functional obstruction on stimulation of diuresis were established at dynamic
      pyeloureterosonography with diuretic load. The differences concerned the strength
      and kind of the reaction, frequency, amplitude and performance of the megaureters
      (15-30-45 min). In vitro studies confirmed functional differences between the
      forms of megaureters. The data obtained show preservation of functional reserves
      of the wall of the refluxing megaureter in children, suppression contractions and
      reaction of the megaureters with organic obstruction in the ureterovesical
      anastomosis while functionally obstructive megaureters are able to contract
      slowly and have reactivity according to the state of the smooth muscle wall.
      Pharmacological impact on ureteral function by metabolic drugs (picamilone) is
      determined. A direct action of lasix on the smooth muscle (weakening of high
      toxic reaction) is proved.

PMID- 16100789
TI  - National Blood Foundation Scientific Research Grants Program: history.

PMID- 16100790
TI  - 6th Canadian Immunization Conference. Montreal, Quebec, 5 to 8 December, 2004.
      Oral scientific abstracts.

PMID- 16100791
TI  - Findings of scientific misconduct.

PMID- 16100792
TI  - Selected non-treatment of neonates: infanticide or ethically justifiable?

PMID- 16100793
TI  - Patient autonomy and consent to treatment: the role of the law?

PMID- 16100794
TI  - Freedom at home: state constitutions and Medicaid funding for abortions.

PMID- 16100795
TI  - Prescribing privacy: the uncertain role of the physician in the protection of
      patient privacy.
AB  - Because medical records are now more comprehensive than ever before, they
      increasingly are being demanded for uses both inside and outside of the medical
      profession. Mr. Gellman contends that existing ethical and legal guidance is
      inadequate to aid physicians in dealing with the confidentiality issues raised
      when patient information is requested or demanded from them, and supports this
      contention by examining the dilemmas faced by physicians presented with such
      requests or demands. He concludes that ethical and judicial guidance will
      continue to be inadequate, and that the only practical way to develop suitable
      guidance is through legislation.

PMID- 16100796
TI  - Laetrile--of choice and effectiveness.

PMID- 16100797
TI  - The concept of brain life: shifting the abortion standard without imposing
      religious values.

PMID- 16100798
TI  - Designer genes: an ethical perspective on genetic manipulation.

PMID- 16100799
TI  - Prenatal v. parental rights: what a difference an "a" makes.

PMID- 16100800
TI  - Modern birth technology and human rights.

PMID- 16100801
TI  - Changing attitudes in Florida's 'right to die' law.

PMID- 16100802
TI  - Refining the definition of death for Australian legislation.
AB  - In the article Mr. Smith considers the need for reform in the area of defining
      when death occurs and the various approaches that exist to define death. He then
      analyses the stages of the developments in the various Australian jurisdictions
      and discusses the substantive content of the basic definition adopted and the
      practical implications of any enactment. The author suggests that the concept of
      death should be legislatively enacted in relevant pieces of legislation which
      call for a resolution of the question at the present time and a more general
      separate statement defining death should be avoided at the moment. Conceptually
      death should be defined as the permanent and irreversible loss of consciousness
      of the individual as determined by irreversible cessation of the brain stem
      function. The actual operational criteria of death should form the subject of a
      circular published by the relevant statutory health authority for the guidance of
      medical practitioners in relation to the specific problems they face.

PMID- 16100803
TI  - Human tissue transplants: legal liability in different jurisdictions.

PMID- 16100804
TI  - Public debates as failed social dramas: the recombinant DNA controversy.

PMID- 16100805
TI  - Refusal of medical treatment: taking respect for the person seriously.

PMID- 16100806
TI  - AIDS and ethical responsibility: some Halachic considerations.

PMID- 16100807
TI  - A reversible decision on consent to sterilization.

PMID- 16100808
TI  - The emergency room admission: how far does the "open door" go?

PMID- 16100809
TI  - New methods of conception and their legal status.

PMID- 16100810
TI  - Critique of the American Psychiatric Association's guidelines for state
      legislation on civil commitment of the mentally ill.

PMID- 16100811
TI  - And some grow mad, and all grow bad: prisoners' constitutional right to receive
      psychiatric treatment.

PMID- 16100812
TI  - Confidentiality laws and state efforts to protect abused or neglected children:
      the need for statutory reform.

PMID- 16100813
TI  - The Report of the Warnock Committee on Human Fertilisation and Embryology.

PMID- 16100814
TI  - "Insuring" the continued solvency of pharmaceutical companies in the face of
      product liability class actions.
AB  - Costly product liability lawsuits continue to plague the pharmaceutical industry,
      and insurance to cover these losses is severely inadequate. Furthermore,
      questionable regulation of drugs exists once a pharmaceutical has passed FDA
      approval. This article describes a plan that uses a capitalistic, rather than a
      governmental, approach to solve both the insurance and the quality control
      problems. Although the proposed plan has never been used to insure pharmaceutical
      companies, different permutations of it have been used to insure other litigation
      prone industries. Success from the proposed insurance entity results from the
      combined knowledge of scientists and actuaries to provide both protection from
      product liability lawsuits for the pharmaceutical industry and enhanced post
      market surveillance of pharmaceuticals.

PMID- 16100815
TI  - Issue dedicated to the memory of Prof Hugo Arechiga Urtuzuastegui on his first
      death anniversary.

PMID- 16100816
TI  - Erratum: Nodal Cooper-pair stabilized phase dynamics in granular d-wave
      superconductors [Phys. Rev. Lett. 92, 037004 (2004)].

PMID- 16100817
TI  - Rethinking paradigms in geriatric ethics.
AB  - This paper calls for a shift away from autonomy as the central value in geriatric
      ethics. In treatment and experimental settings, differences between older and
      younger adults are easily attributed to deficiencies on the part of the elderly
      when autonomy is the central value. Overemphasis on the concept of autonomy skews
      our understanding of human relationships toward excessively rational models,
      distracts attention from important physical and social characteristics of aged
      persons, and results in ethics by default. This paper describes several
      principles that would be more useful starting points than autonomy in developing
      a geriatric ethic.

PMID- 16100818
TI  - Privacy and the regulation of the new reproductive technologies: a decision
      making approach.

PMID- 16100819
TI  - Discrimination and AIDS.

PMID- 16100820
TI  - The Catholic legacy & abortion: a debate.

PMID- 16100821
TI  - The Lutheran ethos and biomedical ethics today.

PMID- 16100822
TI  - Methods of aborting.

PMID- 16100823
TI  - On developing a geriatric ethic: personhood in the thought of Stanley Hauerwas.
AB  - Those who provide health care for the elderly are being confronted by a variety
      of ethical problems, including paternalism, withdrawal of life-support systems,
      and allocation of scarce resources. Discussion surrounding these issues lacks
      persuasive power because it lacks an appropriate theoretical grounding. This
      paper grounds geriatric ethics in the theory of the person described by Stanley
      Hauerwas. It shows that Hauerwas' emphasis on the attributes of temporality,
      sociality, and limitation is both consistent with the conclusions of
      gerontologists, and fruitful for developing specific ethical guidelines. Three
      ethical principles--continuity, interdependence, and normality--provide a
      framework from which to begin to resolve ethical problems in geriatrics.

PMID- 16100824
TI  - Embryo experimentation: a bioethical appraisal.

PMID- 16100825
TI  - Reproductive freedom and women's freedom: surrogacy and autonomy.

PMID- 16100826
TI  - The future of abortion.

PMID- 16100827
TI  - Constitutional analysis of the Baby M decision.

PMID- 16100828
TI  - Biomedical ethics in the year 2000: O = f(H.E.F.).
AB  - The elderly are disproportionate consumers of health care resources. The major
      burden for these health care costs is being borne by the public. As more and more
      of our elderly live longer and consume even more of these finite resources,
      access to these resources will be restricted and they will be placed at ever
      increasing levels of risk. The history, current status, and future "projections"
      for elderly health and health care access are presented.

PMID- 16100829
TI  - Human genetic technology: who shall control?
AB  - The biotechnical "revolution" has fast come upon us. It promises to produce both
      substantial benefits and difficult dilemmas for individuals and society. Despite
      the growing attention being paid to biotechnology, a major unanswered question is
      who shall control the development and use of the powerful array of human genetic
      and reproductive innovations. Should the decisions be left to individual
      consumers and private industry or should they be made by the government or other
      social institutions? After briefly reviewing development in human genetics and
      reproduction and describing trends toward commercialization of them, this article
      discusses the dilemmas these trends raise for a democratic society. It argues for
      the urgent need to delineate societal goals and priorities for the future and for
      technology assessment as early as possible in the developmental process. The
      article concludes by presenting some examples of the social policy problems now
      emerging.

PMID- 16100830
TI  - Defining life: the ethical context for human quality questions.
AB  - The links between ethics, medicine and the law cannot readily produce appropriate
      criteria for human quality questions, largely because ethics are misconstrued
      where they are not excluded; but also because the science at issue is full of
      unknowns. The paper surveys issues in eugenics, abortion and euthanasia.

PMID- 16100832
TI  - Abstracts of the 3rd International Oncology and Nuclear Medicine Conference and
      the 1st International Conference on Paediatric Oncology, Karachi, Pakistan, July
      8-10, 2005.

PMID- 16100831
TI  - Abstracts of the North American Spine Society 20th Annual Meeting, Philadelphia,
      Pennsylvania, USA, September 28-October 1, 2005.

PMID- 16100833
TI  - Drawing lines: the abortion perplex and the presuppositions of applied ethics.

PMID- 16100834
TI  - Bioethics discovers the Bill of Rights.

PMID- 16100835
TI  - High technology health care.

PMID- 16100836
TI  - The price of abortion: sixteen years later.

PMID- 16100837
TI  - Abortion rights: why conservatives are wrong.

PMID- 16100838
TI  - Ethical principles, individual rights, and medical practices.

PMID- 16100839
TI  - The bioengineered competitor? Steroids, hormones, and individual rights.

PMID- 16100840
TI  - Statement for the Third Review Conference of the Biological Weapons Convention.

PMID- 16100841
TI  - Policy on decision making with pregnant patients at the George Washington
      University Hospital.

PMID- 16100842
TI  - Abstracts for the 4th International Conference on Bartonella as Emerging
      Pathogens, 26-28 AUgust 2005, Uppsala, Sweden.

PMID- 16100843
TI  - Antiangiogenic therapy in cancer: a new era has begun.

PMID- 16100844
TI  - [Risk management--informed consent for laryngological surgery and biopsy in
      outpatients].

PMID- 16100845
TI  - Endoscopic oncology.
AB  - Endoscopy plays a critical role in the management of patients with malignancies
      involving the gastrointestinal tract. Endoscopic ultrasound has provided
      essential staging information, made more complete by the ability to perform fine
      needle aspiration of suspicious lymph nodes. Novel endoscopic resection and
      ablative techniques are expanding therapeutic choices in premalignant and
      malignant conditions. Obstruction, virtually anywhere along the length of the
      gastrointestinal tract, can be relieved with new stents. All of these advances
      have made the therapeutic gastroenterologist a key member of the team managing
      patients with tumors of the gastrointestinal tract.

PMID- 16100846
TI  - Effect of dietary magnesium supplementation on bone loss in rats fed a high
      phosphorus diet.
AB  - The purpose of this study was to investigate the effect of dietary magnesium (Mg)
      supplementation on bone loss in rats fed a high phosphorus (P) diet. Weanling
      Wistar strain rats were randomly divided into four dietary groups of 6 rats each
      and fed their respective diets; a diet containing 0.3% P and 0.05% Mg (C), a diet
      containing 1.5% P and 0.05% Mg (HP), a diet containing 0.3% P and 0.15% Mg (HMg),
      or a diet containing 1.5% P and 0.15% Mg (HPMg), for 21 days. Compared to the C
      and HMg groups, serum parathyroid hormone (PTH) concentration was significantly
      higher in the HP and HPMg groups. Serum osteocalcin concentration and urinary
      excretion of C-terminal telopeptides of type I collagen (CTx), markers of bone
      turnover, were significantly higher in the HP and HPMg groups than in the C and
      HMg groups. Dietary Mg supplementation had no significant effects on serum PTH
      and osteocalcin concentrations, while urinary excretion of CTx was significantly
      lower in the HPMg group than in the HP group. These results suggested that
      dietary Mg supplementation suppressed bone resorption due to high P diet.

PMID- 16100847
TI  - Effects of high calcium intake on bone metabolism in magnesium-deficient rats.
AB  - We examined the effects of high calcium (Ca) intake on bone metabolism in
      magnesium (Mg)-deficient rats. Male Wistar rats were divided into three groups,
      with each group having a similar mean body weight, and fed a control diet
      (control group), a Mg-deficient diet (Mg-deficient group) or a Mg-deficient Ca
      supplemented diet (Mg-deficient Ca-supplemented group) for 14 d. Femoral Ca
      content was significantly lower in the Mg-deficient Ca-supplemented group than in
      the control group and Mg-deficient group. Femoral Mg content was significantly
      lower in the Mg-deficient group and Mg-deficient Ca-supplemented group than in
      the control group. Furthermore, femoral Mg content was significantly lower in the
      Mg-deficient Ca-supplemented group than in the Mg-deficient group. Serum
      osteocalcin levels (a biochemical marker of bone formation) were significantly
      lower in the two Mg-deficient groups than in the control group. As a biochemical
      marker of bone resorption, urinary deoxypyridinoline excretion was significantly
      higher in the Mg-deficient Ca-supplemented group than in the control group and Mg
      deficient group. The results in the present study suggest that high Ca intake had
      no preventive effect on alteration of bone metabolism in Mg-deficient rats.

PMID- 16100848
TI  - Erythrocyte magnesium influx and efflux in solid tumor bearing mice.
AB  - Mg metabolism is modified in tumors and tumor-bearing organisms. In particular
      cancer patients often display elevated erythrocyte Mg levels. For a better
      understanding of the increased erythrocyte Mg content, we attempted to determine
      Mg fluxes in erythrocytes from tumor-bearing mice by Mg stable isotopes, using a
      method developed in our laboratory. To characterize the animal Mg status, blood
      and tissue Mg levels and hematological parameters were assayed. Results showed
      that in tumor-bearing mice total erythrocyte Mg was about 46% higher than in
      controls, whereas plasma and tissues Mg levels were not modified; red blood cells
      and hemoglobin as well as hematocrits were significantly decreased, while mean
      corpuscular volume and mean corpuscular hemoglobin were slightly but
      significantly increased in tumor-bearing mice compared to controls (by 3% and 4%,
      respectively), a picture corresponding to a normochromic, slightly macrocytic
      anemia. Erythrocyte Mg efflux was about 20% higher (404 + 59 versus 330 + 45
      micromol/L, respectively, p < 0.05) in tumor-bearing mice compared to controls,
      whereas influx was not significantly modified (130 + 11 versus 122 + 19
      micromol/L, respectively). Our data therefore exclude that the increased Mg
      content observed in erythrocytes of tumor-bearing mice is due to decrease of Mg
      efflux, or to an increase of Mg influx. On the other hand, the increased Mg
      content observed in erythrocytes of tumor-bearing mice could simply result from
      an increase of young Mg-enriched erythrocytes produced by the enhanced
      erythropoiesis which follows tumor-induced anemia.

PMID- 16100849
TI  - Headache due to photosensitive magnesium depletion.
AB  - Clinical and paraclinical data (visual stress tests, electroencephalographic and
      cerebrovascular photic driving, visual evoked potentials) demonstrate that the
      concept of photosensitive headache is fully justified. The interictal hallmark of
      photosensitive cephalalgic patients is potentiation (or sensitization) instead of
      habituation. The aetiopathogenic mechanisms of photosensitive headache associate
      hypofunction of the biological clock and magnesium depletion. The new concept of
      headache due to photosensitive magnesium depletion seems justified. It appears
      logical to add the treatments of magnesium depletion and of photosensitivity to
      classical treatment of headache. Prophylactic magnesium treatment relies on
      atoxic nutritional magnesium supplementation in case of primary magnesium
      deficiency. Pharmacological doses of parenteral magnesium may be used but may
      induce toxicity. Therefore it is necessary to know the therapeutic index of
      magnesium compound used: the larger its value, the greater the safety margin.
      Treatment of photosensitivity uses various types of <<darkness therapies>>:
      darkness therapy through physiologic, psychotherapic, physiotherapic,
      pharmacologic stimulating techniques and substitutive darkness therapy through
      palliative treatment. Melatonin is only a partial substitutive treatment of
      photosensitivity. A new model of photosensitive magnesium depletion with
      potentiation should be a useful tool for discriminating the most efficient gent.

PMID- 16100850
TI  - Magnesium therapy for nephrolithiasis.
AB  - PURPOSE: Critically evaluate the experimental evidence and clinical trial
      outcomes as the basis for use of magnesium (Mg) supplements as therapy for
      calcium oxalate nephrolithiasis. MATERIALS AND METHODS: Literature search of
      MedLine and Web of Science through January 2005; articles cited in papers found
      by searches. RESULTS: Magnesium inhibits calcium oxalate crystallization in human
      urine and model systems. Magnesium also inhibits absorption of dietary oxalate
      from the gut lumen. Three early trials of Mg oxide (MgO) and Mg hydroxide
      (Mg(OH)2) reported lower rates of recurrent stone formation. However in a double
      blind, randomized, placebo-controlled trial with more carefully selected
      patients, there was no significant difference between recurrence rates with 650
      or 1300 mg MgO daily and the placebo. Another trial reported 391 mg (21 meq) Mg
      daily as a mixed salt, Mg potassium citrate, reduced calcium stone recurrence by
      90%, similar to potassium citrate, but with better gastrointestinal tolerance.
      The failure of MgO and Mg(OH)2 as sole therapy may be related to poor absorption
      and low rates of Mg deficiency in the patient populations tested. CONCLUSIONS:
      Clinical trial evidence does not justify the use of MgO or Mg(OH)2 as a sole
      therapy for calcium oxalate kidney stones in a general patient population.
      However, the addition of magnesium to potassium citrate therapy improves
      outcomes. Clinical trials should focus on patients who are likely to be Mg
      deficient.

PMID- 16100851
TI  - Appropriate indications for administration of tPA.

PMID- 16100852
TI  - Use of dipyridamole in patients with recent stroke or TIA.

PMID- 16100853
TI  - Genomic medicine for underserved minority populations in family medicine.

PMID- 16100854
TI  - The role of literacy in health and health care.

PMID- 16100855
TI  - Who filled first-year family medicine residency positions from 1991 to 2004?
AB  - Graduates of U.S. allopathic schools have filled less than one half of the family
      medicine positions offered in the National Resident Matching Program (NRMP) Match
      since 2001. Overall fill rates in July have been relatively stable at
      approximately 94 percent. Family medicine has become reliant on international
      medical graduates (IMGs), who in 2004 made up 38 percent of first-year residents.

PMID- 16100856
TI  - NSAIDs alone or with opioids as therapy for cancer pain.

PMID- 16100857
TI  - Systemic corticosteroids for acute exacerbations of COPD.

PMID- 16100858
TI  - Family history: the three-generation pedigree.
AB  - The collection of a family history ranges from simply asking patients if family
      members have the same presenting illness to diagramming complex medical and
      psychosocial relationships as part of a family genogram. The three-generation
      pedigree provides a pictorial representation of diseases within a family and is
      the most efficient way to assess hereditary influences on disease. Two recent
      events have made family history assessment more important than ever: the
      completion of the Human Genome Project with resultant identification of the
      inherited causes of many diseases, and the establishment of national clinical
      practice guidelines based on systematic reviews of preventive interventions. The
      family history is useful in stratifying a patient's risk for rare single-gene
      disorders and more common diseases with multiple genetic and environmental
      contributions. Major organizations have endorsed using standardized symbols in
      pedigrees to identify inherited contributions to disease.

PMID- 16100859
TI  - Diagnosis and management of uncomplicated urinary tract infections.
AB  - Most uncomplicated urinary tract infections occur in women who are sexually
      active, with far fewer cases occurring in older women, those who are pregnant,
      and in men. Although the incidence of urinary tract infection has not changed
      substantially over the last 10 years, the diagnostic criteria, bacterial
      resistance patterns, and recommended treatment have changed. Escherichia coli is
      the leading cause of urinary tract infections, followed by Staphylococcus
      saprophyticus. Trimethoprim-sulfamethoxazole has been the standard therapy for
      urinary tract infection; however, E. coli is becoming increasingly resistant to
      medications. Many experts support using ciprofloxacin as an alternative and, in
      some cases, as the preferred first-line agent. However, others caution that
      widespread use of ciprofloxacin will promote increased resistance.

PMID- 16100860
TI  - Urinary tract infections: what you should know.

PMID- 16100861
TI  - Health literacy: the gap between physicians and patients.
AB  - Health literacy is basic reading and numerical skills that allow a person to
      function in the health care environment. Even though most adults read at an
      eighth-grade level, and 20 percent of the population reads at or below a fifth
      grade level, most health care materials are written at a 10th-grade level. Older
      patients are particularly affected because their reading and comprehension
      abilities are influenced by their cognition and their vision and hearing status.
      Inadequate health literacy can result in difficulty accessing health care,
      following instructions from a physician, and taking medication properly. Patients
      with inadequate health literacy are more likely to be hospitalized than patients
      with adequate skills. Patients understand medical information better when spoken
      to slowly, simple words are used, and a restricted amount of information is
      presented. For optimal comprehension and compliance, patient education material
      should be written at a sixth-grade or lower reading level, preferably including
      pictures and illustrations. All patients prefer reading medical information
      written in dear and concise language. Physicians should be alert to this problem
      because most patients are unwilling to admit that they have literacy problems.

PMID- 16100862
TI  - Child safety seat counseling: three keys to safety.
AB  - The number one cause of death for children younger than 14 years is vehicular
      injury. Child safety seats and automobile safety belts protect children in a
      crash if they are used correctly, but if a child does not fit in the restraint
      correctly, it can lead to injury. A child safety seat should be used until the
      child correctly fits into an adult seat belt. It is important for physicians
      caring for children to know what child safety seats are available and which types
      of seats are safest. Three memory keys will help guide appropriate child safety
      seat choice: (1) Backwards is Best; (2) 20-40-80; and (3) Boost Until Big Enough.
      "Backwards is Best" cues the physician that infants are safest in a head-on crash
      when they are facing backward. "20-40-80" reminds the physician that children may
      need to transition to a different seat when they reach 20, 40, or 80 lb. "Boost
      Until Big Enough" emphasizes that children need to use booster seats until they
      are big enough to fit properly into an adult safety belt.

PMID- 16100863
TI  - Car safety for your child.

PMID- 16100864
TI  - A 40-year-old man with chronic generalized rash.

PMID- 16100865
TI  - Treatment of early Parkinson's disease.

PMID- 16100866
TI  - Newly defined central nervous system neoplasms.
AB  - In recent years, numerous new entities or variants of recognized central nervous
      system tumors have been described in the literature, and the morphologic spectrum
      of these neoplasms is delineated incompletely. The accurate diagnosis and
      classification of these lesions is important to ensure that patients receive
      adequate therapy and prognostic information. The clinicopathologic features and
      differential diagnosis of 4 new entities, including the chordoid glioma of the
      third ventricle, cerebellar liponeurocytoma, atypical teratoid/rhabdoid tumor,
      and papillary glioneuronal tumor, are discussed in this review.

PMID- 16100867
TI  - Serous and mucinous borderline (low malignant potential) tumors of the ovary.
AB  - The prognosis for stage I serous borderline ovarian tumors (SBOTs) is thought to
      be excellent, despite rare, late recurrences. The behavior of advanced-stage
      SBOTs primarily depends on the invasiveness vs noninvasiveness of associated
      extraovarian implants. Pelvic and abdominal lymph node involvement and foci of
      microinvasion do not seem to adversely affect prognosis. Serous tumors with a
      micropapillary and/or cribriform growth pattern seem to be more frequently
      bilateral and exophytic and manifest at an advanced stage with a higher incidence
      of invasive implants than typical SBOTs. Molecular data suggest that such tumors
      may represent an intermediate stage in the typical SBOT-invasive low-grade serous
      carcinoma progression. Limited experience with endocervical (mullerian)-type
      mucinous borderline tumors shows a possible relation to SBOTs in
      clinicopathologic features and biologic behavior Intestinal-type mucinous
      borderline ovarian tumors (I-MBOTs) and well-differentiated mucinous carcinomas
      manifest at stage I in most cases; the prognosis is excellent. Mucinous tumors
      associated with pseudomyxoma peritonei are almost always secondary to similar
      tumors of the appendix or other gastrointestinal sites and should not be
      diagnosed as high-stage I-MBOTs. Rare primary ovarian mucinous tumors associated
      with pseudomyxoma peritonei are those arising in mature cystic teratomas.
      Advanced-stage ovarian mucinous carcinomas typically show frank, infiltrative
      type invasion; the prognosis is poor.

PMID- 16100868
TI  - Gleason grading and volume estimation in prostate needle biopsy specimens:
      evolving issues.
AB  - The Gleason grading system for prostate cancer is a powerful tool that can help
      choose therapy and predict outcome for patients. The clinical use and problem
      areas of the Gleason grading system are reviewed. The issues discussed include
      grade discrepancies between prostate biopsy and resection specimens, grading
      small foci of tumor, diagnosing and grading cribriform lesions, reporting the
      grade when 3 grades of cancer are present in a specimen, and assignment of grade
      when multiple cores of differing grades are present. Finally, differing ways of
      communicating tumor volume and the percentage of high-grade carcinoma in prostate
      biopsy cores are considered.

PMID- 16100869
TI  - Current concepts in the classification of interstitial lung disease.
AB  - The diagnosis and classification of idiopathic interstitial pneumonias continue
      to be problematic areas for pathologists. The recently proposed American Thoracic
      Society/European Respiratory Society International Multidisciplinary Consensus
      Classification of the Idiopathic Interstitial Pneumonias defines specific
      clinical, radiologic, and pathologic criteria for each of the pulmonary disorders
      that encompass the idiopathic interstitial pneumonias. In this review, the
      highlights of this classification are presented, along with recommended
      guidelines for handling lung biopsy specimens and diagnosing interstitial lung
      diseases.

PMID- 16100870
TI  - Chemokines and their receptors: roles in specific clinical conditions and
      measurement in the clinical laboratory.
AB  - Considerable progress has been achieved in our knowledge of the function of the
      chemokine system and in understanding its role in the pathophysiology of human
      diseases. This complex system, presently including approximately 50 cytokines and
      20 receptors, coordinates leukocyte recruitment in a variety of human diseases,
      ranging from infectious and inflammatory diseases to cancer. A large body of
      literature has been published describing various assays for the measurement of
      chemokines in biologic fluids and tissues. We review information available on the
      role of chemokines in selected human diseases and provide examples of clinical
      situations in which chemokine determination might be of practical value, and we
      describe the currently available assays for their measurement.

PMID- 16100871
TI  - Effects of alcohol on hemostasis.
AB  - Several epidemiologic studies have shown that moderate intake of alcohol is
      associated with a lower risk of cardiovascular disease (CVD), but the mechanism
      is not fully elucidated. One of the proposed mechanisms of the protective effect
      of moderate alcohol intake is its beneficial effect on hemostasis. The aim of
      this review is to summarize the effect of ethanol intake on platelet aggregation
      and activation, coagulation factors including von Willebrand factor (vWF), and
      the fibrinolytic system. With regard to the effect of alcohol on platelet
      function, evidence in the literature suggests both platelet activation and
      platelet inhibition by ethanol. A unifying hypothesis is that platelets are
      partially activated by ethanol, with partial degranulation allowing for continued
      circulation of platelets with impaired function. Evidence also exists showing
      that ethanol intake decreases fibrinogen, factor VII, and vWF levels. In
      addition, alcohol intake has been found to increase fibrinolysis by increasing
      tissue plasminogen activator activity. The effect of ethanol on platelets,
      coagulation factors, and the fibrinolytic system is likely to contribute to
      protection against CVD.

PMID- 16100872
TI  - Endomyocardial biopsy for non-transplant-related disorders.
AB  - Endomyocardial biopsy (EMB) remains the "gold standard" for diagnosing rejection
      after cardiac transplantation. In addition, it has value in monitoring patients
      during treatment with doxorubicin. It also is important in the setting of acute
      onset heart failure for the diagnosis of myocarditis, particularly giant cell
      myocarditis because earlier transplantation usually is undertaken in patients
      with giant cell morphologic features. EMB has a role in the unexplained
      cardiomyoapthy for excluding specific disease processes that might lead to
      similar morphofunctional changes but might be reversible or a contraindication
      for transplantation. This review focuses on the growing number of diseases that
      can be diagnosed by EMB in adult and pediatric age groups.

PMID- 16100873
TI  - Children with signs of abuse: when is it not child abuse?
AB  - Child abuse is a problem that is frequently underdiagnosed. Recognition that
      underdiagnosis of abuse exists has produced a high zeal for identifying cases of
      child abuse, which has inevitably produced cases of overdiagnosis. Overdiagnosis
      of child abuse is as catastrophic as underdiagnosis. In this case, a family
      member is often accused of injuring or killing a child at a time when the loss is
      felt most deeply. This review focuses on 1 specific presentation of child abuse-
      the child with bruises and bleeding. Many children and adults have coagulation or
      vascular disorders that predispose them to bruise or bleed excessively with minor
      trauma. It is very easy for a health care worker to presume that bruising and
      bleeding is associated with trauma, because the coagulopathies that may explain
      the findings are often poorly understood. The clinical cases reviewed in this
      article show the need for an extremely thorough analysis for an underlying
      bleeding disorder in the bruised or bleeding child being evaluated as a possible
      victim of child abuse.

PMID- 16100874
TI  - Aspirin resistance: moving forward with multiple definitions, different assays,
      and a clinical imperative.
AB  - Many patients are treated with aspirin to prevent a serious vascular event, most
      notably myocardial infarction and stroke. A growing number of studies have been
      appearing in the literature that indicate a significant fraction of aspirin
      treated patients may be resistant to the antiplatelet effects of the drug.
      Resistance to aspirin may be related to the concomitant ingestion of aspirin and
      nonsteroidal anti-inflammatory drugs, which impairs the aspirin effect, or to
      more complex situations, such as metabolic defects that diminish the therapeutic
      effect of aspirin. The incidence of aspirin resistance is unknown, but it may
      approach 20% to 30%. The diagnosis of aspirin resistance has been evaluated using
      multiple assays, and because there are multiple assays, this has resulted in
      multiple definitions for aspirin resistance. This review considers aspirin
      resistance at a time when there is confusion about the definition, and the
      clinical assay to best assess it, because there is a clinical imperative to know
      now which patients taking aspirin are not receiving a therapeutic effect.

PMID- 16100875
TI  - Don't let the dissenters distort the medical profession's perspective on
      treatment for HIV/AIDS.

PMID- 16100876
TI  - The 'worried-well', insulin resistance and metformin therapy.

PMID- 16100877
TI  - The limits of medical science and the right to procreate.

PMID- 16100878
TI  - Cover caption contested.

PMID- 16100879
TI  - A costly waiting game.

PMID- 16100880
TI  - Government 'encouraging snake-oil salesman' Rath.

PMID- 16100881
TI  - Payouts against doctors spiralling upward.

PMID- 16100882
TI  - Medical aid schemes--guarding the guardians.

PMID- 16100883
TI  - Incorrect use of a homemade spacer for treatment of recurrent wheezing in
      children--a cause for concern.

PMID- 16100884
TI  - Use of phenobarbitone for treating childhood epilepsy in resource-poor countries.

PMID- 16100885
TI  - Intracranial mycotic aneurysm due to infective endocarditis--successful NBCA glue
      embolisation.

PMID- 16100886
TI  - Proposed guidelines for malaria antigen testing.

PMID- 16100887
TI  - Playstation thumb--a new epidemic in children.

PMID- 16100888
TI  - Where have all the doctors gone? Career choices of Wits medical graduates.
AB  - OBJECTIVES: To assess the distribution of University of the Witwatersrand (Wits)
      medical graduates from 1960 to 1994 with regard to private or public sector work,
      chosen specialist or generalist careers, and work in urban or rural areas,
      looking for secular trends and gender differences. DESIGN: A cross-sectional
      analysis of the register of what was then the South African Medical and Dental
      Council (SAMDC) and a telephone interview survey of a sample of medical
      graduates, collecting retrospective career histories. RESULTS: Thirty-six per
      cent of the sample was working predominantly in the public sector, while 47% of
      all years worked by graduates were in the public sector. Women graduates spent
      68% of their years working in the public sector, compared with 36% for men. The
      majority (55%) of graduates in the sample who were working in the public sector
      cited academic and training aspects as the main reason for this choice.
      Conversely, nearly half (47%) gave income as the main reason for moving to the
      private sector. Forty per cent of graduates had specialised (46% of men, 22% of
      women), while 76% were working in the large urban areas. CONCLUSIONS: The
      findings highlight methodological problems with standard cross-sectional analysis
      of distribution of personnel. They also challenge several assumptions about the
      likelihood of Wits graduates working as generalists (60%), the voluntary
      contribution of graduates to the public sector, and in particular the value of
      women doctors to public service and primary care.

PMID- 16100889
TI  - Pleading the defence of therapeutic privilege.

PMID- 16100890
TI  - Withdrawal of parenteral phenobarbitone--implications for resource-poor
      countries.
AB  - Parenteral phenobarbitone is an integral part of the management of status
      epilepticus, especially in the context of resource-poor countries. It is highly
      effective at controlling seizures. It is safe, cheap, can be given by rapid
      intravenous push or intramuscular route, boluses can be repeated, and it is
      recommended as part of the Advanced Paediatric Life Support guidelines. The
      proposed alternatives lack efficacy, practicality and/or place the child in
      status epilepticus at risk of respiratory compromise. The impact of the loss of
      parenteral phenobarbitone would be increased cardiac complications, lack of early
      seizure control, prolonged seizures resulting in brain damage and systemic
      complications. Increased numbers of patients will require artificial ventilation
      in centres without facilities, and centres with facilities will be unable to cope
      with the load of ventilated patients because of lack of safe transport systems
      and bed space.

PMID- 16100891
TI  - Demographics and presenting clinical features of childhood systemic lupus
      erythematosus.
AB  - OBJECTIVES: To review the presentation and characteristics of children with
      systemic lupus erythematosus (SLE). METHODS: The records of children with
      sufficient American College of Rheumatology (ACR) criteria for SLE treated by the
      renal units of the Johannesburg and Chris Hani Baragwanath hospitals, and the
      arthritis clinic of the Johannesburg Hospital between January 1974 and March 2000
      were reviewed. The clinical presentation, age distribution and race were
      examined. RESULTS: A total of 36 children met the criteria. There were 26 girls
      and 10 boys, with a mean age of 11.5 and 10.2 years respectively. The male-to
      female ratio was 1:2.6 overall, with a ratio of 1:1.2 under 10 years and 1:4 over
      10 years. There were 15 white, 2 Indian and 5 coloured patients. The 14 black
      patients all presented after 1986. Rashes were found to be the commonest clinical
      feature present at the time of diagnosis, followed by polyarthritis and renal
      pathology. Constitutional symptoms were common, as were generalised
      lymphadenopathy and hepatosplenomegaly, while neurological, pulmonary and cardiac
      signs and symptoms were less common. Renal disease was present in 58% of patients
      on presentation. CONCLUSION: There is a diverse array of presenting features in
      childhood SLE. There has been increased recognition of the disease in young black
      South Africans since 1986.

PMID- 16100892
TI  - Cannabis and other drug use among trauma patients in three South African cities,
      1999-2001.
AB  - OBJECTIVE: To assess the extent of cannabis and other drug use among patients
      presenting with recent injuries at trauma units in Cape Town, Port Elizabeth and
      Durban from 1999 to 2001. DESIGN: Cross-sectional surveys were conducted during a
      4-week period at each of the above sites in 1999, 2000 and 2001. The concept of
      an idealised week was used to render representative samples. OUTCOME MEASURES:
      Cause of injury and biological markers to assess use of cannabis, methaqualone
      (Mandrax), opiates, cocaine, amphetamine, and methamphetamine. RESULTS: Over half
      of all patients tested experienced violent injuries. Excluding opiates, across
      sites and over time between 33% and 62% of patients tested positive for at least
      one drug (N = 1565). In most cases the drugs were cannabis and/or methaqualone.
      While no inter-city differences were found, male patients were typically more
      likely to test positive for drugs in general and specific drugs such as cannabis
      and the cannabis/methaqualone ('white pipe') combination than female patients.
      Drug positivity was higher in 2001 than in the previous 2 years in Cape Town, and
      patients injured as a result of violence in Cape Town and Durban were more likely
      to test positive for drugs than patients with certain other types of injuries.
      CONCLUSIONS: Drug use among trauma patients has remained consistently high for
      each of the 3 study periods. Efforts to combat the abuse of drugs such as
      cannabis and methaqualone would appear to be paramount in reducing the burden of
      injuries on health care services. The study has raised numerous issues requiring
      further research.

PMID- 16100893
TI  - [Collagen transformation in organism: modern state of the problem].
AB  - Collagens, which compose 1/3 of total proteins in the organism, have unique
      chemical structure and biological role. Current state of the investigation of
      these proteins biosynthesis and catabolism, role of shaperones, prolyl- and
      lysiloxydases, glycosyltransferases, metalloproteinases and other enzymes in
      collagens metabolism, as well as biological activities of collagens and their
      fragments have been considered in the review.

PMID- 16100894
TI  - [Cytochrome P4502E1. Polymorphism, physiological function, regulation, and role
      in pathology].
AB  - The role of cytochrome P4502E1 in metabolism of substances, polymorphism, ways of
      the expression regulation, change of activity in pathological condition is
      considered in the review. Cytochrome P4502E1 catalyzed first two reactions of
      acetone transformation in the lactic acid, ethanol oxidation, metabolism of fatty
      acids and their hydroperoxides. Cytochrome P4502E1 dependent metabolism of
      xenobiotics in many cases results in formation of toxic intermediates and
      radicals of oxygen. Regulation of cytochrome P4502E1 expression includes
      transcriptional mechanisms and substrate stabilization of its molecule. The
      enzyme activity grows in alcoholism, diabetes mellitus, obesity, steatohepatitis,
      administration of acetone, alcohols and is connected with intensification of
      toxicity of paracetamol, halothane, benzene, tetrachlororomethane and others
      xenobiotics. Such inhibitors of cytochrome P4502E1 as dialyl sulphide, disulfiram
      have hepatoprotective action.

PMID- 16100895
TI  - [Biosynthesis of poppy isoquinoline alkaloids in nature and in vitro culture. 2.
      Bracteum poppy (Papaver bracteatum Lindl.)].
AB  - Literature data and the data of the author's investigations on production of
      isoquinoline alkaloids by Papaver bracteatum Lindl. have been analyzed.
      Information on the methods of regulation and cell localization of morphine and
      sanguinarine biosynthesis is presented. The works studying differentiation
      processes in tissue cultures of bracteum poppy and relationship thereof with
      thebaine biosynthesis have been analyzed. Possible mechanism determining the
      induction of somatic embryos development and thebaine biosynthesis in the culture
      in vitro are proposed.

PMID- 16100896
TI  - [Identification and catalytic properties of Mg2+-dependent ATP-hydrolase of
      cytoplasmic membrane of Bacillus sp. B4253 capable of gold accumulation].
AB  - Ca2+-independent, Mg2+-dependent ATP-hydrolase fermentative activity consisting
      of two components--azide-sensitive and azide-resistant ones has been identified
      in cytoplasmic membrane of Bacillus sp. B4253 capable to gold accumulation in
      ionic and colloid forms. The authors have characterized properties of the azide
      resistant component of ATP-hydrolase reaction: dynamics of accumulation of one of
      the reaction products--inorganic phosphate P(i); dependence of ATP hydrolysis
      rate on the membrane protein content; pH-dependence; sensitivity of ATP-hydrolase
      activity to the change of reagents (ATP, Mg2+) concentration, as well as to the
      effect of some specific and nonspecific inhibitors of ion-transporting Mg2+
      dependent ATP-hydrolase systems (ouabain, tapsigargin, eocine Y, La ions). It is
      supposed that the obtained experimental data can be used for the following study
      of molecular and membrane mechanisms of gold accumulation in Bacillus sp. B4253.

PMID- 16100897
TI  - [Effect of Mg ions and spermine on ATP-dependent Ca2+ transport in myometrial
      intracellular structures. I. Comparative study of Ca2+ accumulation in
      mitochondria and sarcoplasmic reticulum].
AB  - In experiments, which were carried out with the use of a radioactive label
      (45Ca2+) on the suspension of rat uterus myocytes treated by digitonin solution
      (0.1 mg/ml), influence of Mg ions and spermine on Mg2+, ATP-dependent Ca2+
      transport in mitochondria and sarcoplasmic reticulum was investigated. Ca2+
      accumulation in mitochondria (1324 +/- 174 pmol Ca2+/10(6) cells for 1 min - the
      control) was tested as such which was not sensitive to thapsigargin (100 nM) and
      was blocked by ruthenium red (10 microM). Oxalate-stimulated Ca2+ accumulation in
      sarcoplasmic reticulum (136 +/- 17 pmol Ca2+/10(6) cells for 1 min - the control)
      was tested as such which was not sensitive to ruthenium red and was blocked by
      thapsigargin. It has been shown, that initial speed and level of energy-dependent
      Ca2+ accumulation in mitochondria considerably exceeded the values of these
      parameters for sarcoplasmic reticulum Ca2+-accumulation system. Ca2+ accumulation
      kinetic in mitochondria was characterized by a steady-state phase (for 5-10 min.
      of incubation) while accumulation kinetic of this cation in sarcoplasmic
      reticulum corresponded to zero order reaction. Increase of Mg2+ concentration up
      to 5 mM led to activation of Ca2+-accumulation systems in mitochondria and
      sarcoplasmic reticulum (values of activation constants K(Mg) for Mg2+ were 2.8
      and 0.6 mM, accordingly). Concentration dependence of spermine action on Ca2+
      accumulation in mitochondria was described by a dome-shaped curve with a maximum
      at 1 mM spermine. In case of sarcoplasmic reticulum Ca2+ pump only the inhibition
      phase was tested at spermine concentration above 1 mM. However values of
      inhibition constants for both transporting systems were practically identical-
      5.2 +/- 0.6 and 5.7 +/- 0.7 mM, accordingly. Hence, Mg ions carry out the
      important role in regulation of energy-dependent Ca2+ transporting systems both
      in uterus smooth muscle mitochondria and sarcoplasmic reticulum. Spermine acts
      first of all on mitochondrial calcium uniporter.

PMID- 16100898
TI  - [Decrease of mitochondrial sensitivity to Ca2+-induced pore opening during long
      term incubation].
AB  - It is shown that mitochondria of rat myocardium exhibit high sensitivity to Ca2+
      induced permeability transition pore (PTP) during an hour after their isolation.
      The threshold Ca2+ concentrations necessary to induce PTP are as low as 25-50
      nmol/mg of protein. Apparent K(Ca) constant of Ca2+-dependent PTP activation is
      40 microM. Incubation of mitochondria during 2, 3 and 4 hours after their
      isolation leads to gradual increase in K(Ca) values up to 0.4 microM, which is
      accompanied by simultaneous decrease in sensitivity of mitochondria to pore
      opening. A correlation is supposed between changes of kinetic parameters of Ca2+
      uniporter and changes in sensitivity of mitochondria to Ca2+-induced permeability
      transition.

PMID- 16100899
TI  - [Lipid-mobilizing effect of reduced glutathione and its intensifying action on
      lecithin-cholesterol acyltransferase activity in blood serum of rats].
AB  - Effect of reduced glutathione (50 mg/100 g) on lipid distribution between organs
      (liver and kidney) and lecithin-cholesterol acyltransferase (LCAT) activity in
      blood serum of rats was investigated. The accumulation of common lipids as a
      result of speeding up the absorbtion of blood serum unsaturated fatty acids and
      relative decrease of lipids unsaturation in the liver and lipid content dynamics
      in kidneys owing to the intensification of two processes in this organ: the
      transport of polyene fatty acids in composition of blood serum lipoprotein lipids
      to kidney cells and peroxidation of membrane phospholipids were found out. The
      activating effect of GSH (in vivo and in vitro) on LCAT activity of rat blood
      serum was shown. It was summarised that GSH-intensification of blood serum
      etherification ability may be a basic component of reduced glutathione lipid
      mobilization effect.

PMID- 16100900
TI  - [Binding of alpha-2-antiplasmin with fibrinogen/fibrin and their fragments
      independent of factor XIII].
AB  - Possible interaction of alpha-2-antiplasmin with fibrinogen, fibrin and their
      fragments independent of factor XIII as well as the inhibitor effect on the Glu
      plasminogen activation by tissue activator were studied. It was shown that alpha
      2-antiplasmin is adsorbed on desAA- and desAABBfibrin films (Kd 69.0 +/- 1.0 nM
      68.6 +/- 5.3 nM, respectively). Glu-Plasminogen has no effect on the inhibitor
      binding with desAABBfibrin. Alpha-2-antiplasmin shows strong affinity for fibrin
      D-dimer (Kd 65.0 +/- 4.0 nM) and D-fragment of fibrinogen (Kd 119.0 +/- 21.0 nM),
      but it does not interact with E-fragment. The inhibitor inside the fibrin clot
      decreases 10 times the activation rate of Glu-plasminogen by the tissue activator
      both is the presence and without factor XIII at physiological ratio of Glu
      plasminogen, tissue activator, fibrin and alpha-2-antiplasmin. Thus we have shown
      that fibrinogen/fibrin binds alpha-2-antiplasmin independent of the factor XIII.
      Binding sites of the inhibitor are localized in D-fragment of fibrinogen and/or
      fibrin D-dimer. Alpha-2-antiplasmin inhibits the Glu-plasminogen activation by
      tissue activator on fibrin.

PMID- 16100901
TI  - [Effect of carboxylate and Na ions on the tautomeric status of 9-methylguanine].
AB  - Interactions of 9-methylguanine (m9Gua) with carboxylate ion of acetic acid
      (CH3COO-) and Na+ were studied by 1H NMR spectroscopy and ab initio quantum
      chemical calculations of the B3LYP/6-31++G(d,p) and B3LYP/6-311++G(d,p) levels of
      theory. Changes in the m9Gua 1H NMR spectrum in the presence of the equimolar
      amount of sodium acetate (NaAc), which in anhydrous DMSO dissociates to CH3COO-
      and Na+, were interpreted as a consequence of a complex formation of m9Gua in the
      amino-keto-N1H tautomeric form (m9GuaN1H) with carboxylate ions via two H-bonds
      involving amino and N1H-imino protons. Quantum chemical calculations of
      interactions of the m9GuaN1H ground-state tautomer and the m9GuaN3H high energy
      one with relative energy 20.01 kcal/mol show that the ground state tautomer forms
      the ground-state complex CH3COO-:mgGuaN1H, by 5.57 kcal/mol more stable than the
      CH3COO-:m9GuaN3H complex, and coordination of Na+ with the O6 and N7 atoms
      reduces this energy difference to 2.57 kcal/mol. Such a coordination of Na+ with
      tautomer m9GuaN3H therewith decreases its relative energy only to 13.31 kcal/mol.
      Non-additivity of the two ligands contributions to the 8-times reduction of the
      relative energy of the high energy tautomer in the CH3COO-:m9GuaN3H:Na+(O6,N7)
      triple complex was concluded, the role of CH3COO- being dominant. Besides,
      coordination with Na+ resulted in an iminoproton transfer from the base to CH3COO
      in the triple complexes of both tautomers, according to calculations in vacuum.
      Biological significance of the results is noticed.

PMID- 16100902
TI  - [Thrombospondin-1-dependent mechanism of transforming growth factor beta-1
      activation in cultured human endothelial cells].
AB  - Using two immortal human umbilical vein endothelial-derived cell lines we
      investigated the thrombospondin-1 (TSP-1)-dependent mechanism of the transforming
      growth factor beta-1 (TGFbeta1) activation. Exogenous human platelet TSP-1 was
      demonstrated to increase (1.7-2.0-folds) the concentration of active TGFbeta1
      produced by both cell lines, but did not influence the concentration of total
      TGFbeta1. The process of TGFbeta1 activation is known to be regulated by
      G418GWSHW423 fragment of TSP-1 molecule. The simultaneous addition of TSP-1 and
      100-fold molar excess (about TSP-1) of the synthetic GGWSHW peptide abolished TSP
      1-induced TGFbeta1 activation. GGWSHW peptide inhibited the basal activation of
      TGFbeta1 in endothelial cells, whereas the secretion of total TGFbeta1 and TSP-1
      was not altered. We conclude that TSP-1-dependent mechanism of endogenous
      TGFbeta1 activation is operation in human endothelial cells.

PMID- 16100903
TI  - [Changes of chromatin structure state in thymocites at the early stage of
      apoptosis induced by hydrogen peroxide and radiation].
AB  - The paper deals with changes in the structural state of chromatin in isolated
      thymocites at the early stage of apoptosis induced by hydrogen peroxide and
      radiation. Content of necrosis and apoptosis cells in the suspension of the
      isolated rat thymocites, during 3-hour incubation after X-ray irradiation in a
      dose of 4.5 Gy or with the presence of 0.1 microM of H2O2 by the method of double
      lifetime staining by fluorescent dye Hehst 33342 and propydium iodide has been
      estimated. Apoptogenic effect of the studied effects has been found out, the
      dynamics of condensation and internucleosomic chromatin fragmentation has been
      established. It has been shown that 100 microM alpha-tocopherol inhibited
      completely DNA fragmentation in the cells incubated with H2O2 and only partially
      in irradiated cells. Introduction of postmitochondrial supernatant, isolated from
      the incubated control or irradiated cells, into the cell-free system which
      included the ATP-regenerating system and nuclei of control thymocites did not
      affect the level of DNA fragmentation, while the increase of the level of
      fragmented DNA in nuclei was observed in the presence of the supernatant obtained
      by centrifugation of the cells treated by H2O2. Differences of mechanisms of
      thymocite apoptosis initiation, as affected by hydrogen peroxide and ionizing
      radiation, is discussed.

PMID- 16100904
TI  - [Role of phosphatidylinositol 3-kinase in platelet aggregation in type 1 diabetes
      mellitus].
AB  - It was found that incubation of platelet rich plasma with wortmannin, an
      irreversible selective inhibitor of phosphoinositide 3-kinase (PI3K), leads to
      sharp drop in platelet aggregation ability in healthy donors, whereas in type 1
      diabetes mellitus patients this effect was less manifested or not quite
      determined. Translocation dynamics of PI3K regulatory subunit into cytoskeleton
      fraction under induction of platelet aggregation by various ADP concentrations
      and after wortmannin treatment was studied. Reciprocal interaction of endothelial
      constitutive NO synthase with PI3K in mechanisms of platelet functional state
      regulation under studied pathological and normal conditions have been analyzed.

PMID- 16100905
TI  - [Intensity of lipids peroxidation and state of antioxidant protective system in
      calves, which have had dyspepsia].
AB  - The intensive development of lipids peroxidation with simultaneous deficit of
      antioxidant protective factors in organism of calves, which have had neonathal
      enteropathology was shown. The effectiveness of phospolipid preparation FLP-MD,
      which makes antioxidant protective mechanisms stronger during this pathological
      state, and may be recommended as a drug for reparation therapy in complex scheme
      of dyspepsia medical treatment and proves a necessity of the antioxidant
      preparations application.

PMID- 16100906
TI  - [Oxidative and free-radical processes in the mechanism of toxic effect of anti
      diabetic drugs dicarboxylic acids derivatives].
AB  - Dynamics of changes in the processes of the lipids free-radical peroxide
      oxidation (LPO), state of the monooxygenase system (MOS) and system of anti
      oxidant protection (SAOP) in the liver and blood of rats under multiple peroral
      and inhalatory expositions of anti-diabetic drugs--dicarboxylic acids
      derivatives: phensuccinalum (PhS) and diacamph (Dc) in toxic and sub-toxic doses
      is studied. It has been found that one of the key biochemical mechanisms which
      determines the early signs of the toxic damage in the cells and organism under
      the effect of certain doses/concentrations of PhS (500 and 100 mg/kg, 20.2 mg/m3)
      and Dc (1000 mg/kg) consists in intensification of the free-radical processes,
      including, in particular, LPO combined with activation of MOGS and inhibition of
      SAOP in microsomal fraction of the liver. The high significance of changes of
      researched parameters for an assessment or forecasting of toxicity of
      dicarboxylic acids derivates is shown. Unlike the liver, the PhS and Dc impact on
      the blood caused changes of compensatory-adaptive nature in the LPO and SAOP
      systems.

PMID- 16100907
TI  - [Modulating effect of helium-neon laser radiation on the state of antioxidant and
      hydroxylation systems of quail liver under X-ray irradiation and chemical
      intoxication].
AB  - Red laser light (lambda = 633 nm) in a dose of 9.5 mJ/cm2 defends quail's embryo
      from X-ray irradiation (8.5 Gr). It is expressed in the 1.9 times decrease of
      embryo mortality on early term of incubation and 1.6 times increase of hatch in a
      group of embryos, which were affected by X-rays and laser radiation compared with
      an embryo, irradiated only by X-rays. Repeated laser irradiation of adult quails
      (dose 21 J) after CCl4-intoxication led to normalization of hydroxylation and
      antioxidant systems functions.

PMID- 16100908
TI  - [Neuroprotective effect of N-acylethanolamines in chronic morphine dependence. I.
      Rat brain phospholipids as a target of their action].
AB  - The influence of saturated and unsaturated N-acylethanolamines (NAEs) mixture on
      the rat brain lipid composition under the chronic morphine dependence was
      studied. It was shown that the long-term administration of NAE to rats with
      experimental morphine dependence restored the morphine-induced alterations of the
      brain phospholipid composition. This effect can probably be explained by a fatty
      acyl transfer from NAE to sn-1 position of some brain glycerophospholipids.
      Another reason of NAE beneficial effect could be due to its antioxidative
      property, thus providing the remodelling of phospholipid composition. The
      restoration of the brain essential phospholipids is associated with the decline
      in morphine consumption in rats with experimental morphine dependence. The
      mechanism of this phenomenon requires further investigations.

PMID- 16100909
TI  - [Specific and nonspecific interactions of antibodies and immunoglobulins with
      antigens and the methods of analysis of these interactions].
AB  - The problem of specific and nonspecific interaction of serum immunoglobulins and
      antigens was considered. It was shown that high-sensitive methods allow to reveal
      low-affinity non-specific interaction of immunoglobulins and antigens. If the
      concentration of the specific antibodies in a studied sample of serum is low, the
      non-specific interaction of serum immunoglobulins may exceed substantially the
      effect of specific reaction. In this case the obtained results could be
      misinterpreted. In this connection the conclusion has been done that in such a
      case it is necessary to take into account the capability of serum immunoglobulins
      to interact non-specifically with antigens and to discriminate between specific
      and non-specific interaction. The methods of the diminishing the non-specific
      interaction are suggested.

PMID- 16100910
TI  - [Catalase activity as affected by carnosine and sodium nitrite in vitro].
AB  - It was shown in vitro that the activity of catalase Penicillium vitale decreases
      when treated by sodium nitrite to the greater extent than when affected by
      dipeptide carnosine (beta-alanyl-L-histidine). At alternating introduction of
      carnosine and NaNO2 that component affected the catalase activity which was the
      first to be introduced. The entering of the next metabolite into the medium did
      not change the enzyme activity. It is shown that carnosine binds with a molecule
      of catalase. Carnosine may be considered one of natural regulators of catalase
      activity.

PMID- 16100911
TI  - [Effect of melatonin and radiation on pro- and antioxidant state of the liver and
      blood of rats].
AB  - The pro- and antioxidant state of the liver and blood of rats under the effect of
      melatonin and radiation in the total dose of 20 Gy has been studied. Irradiation
      by the broad fields intensifies the processes of lipoperoxidation and oxidative
      modification of proteins with simultaneous inhibition of the antioxidant
      protection. Melatonin administered against a background of radiation caused a
      distinctly expressed antioxidant effect.

PMID- 16100912
TI  - [Decrease of mutagenic action of cyclophosphamide by buckwheat melanin
      preparation].
AB  - Melanins are polyphenolic pigments of plants, animals and microbes with
      antioxidant and antiradiation activity. Water-soluble melanin from buckwheat is
      experienced as antimutagenic means (0.01-10 mg/kg per os) for cyclophosphamide
      (20 mg/kg i.p.) in the 3 series of experiments. The frequency of chromosome
      aberrations in the cells of mice bone marrow after mutagene is reduced 2-6 times
      once under influence of melanin.

PMID- 16100913
TI  - [Comparative study of enzymatic activity of cholinesterases of different origin
      in thionaphthylacetate hydrolysis reactions].
AB  - A comparative determination of kinetic parameters V and Km in the reaction of
      hydrolysis thionaphthylacetate and well known substrate acetylthiocholine by
      choline esterases from different sources was conducted. It is shown that
      butyrylcholine esterases hydrolyze thionaphthylacetate with velocity comparable
      with that of hydrolysis of acetylthiocholine, while acetylcholine esterases and
      propionylcholine esterases hydrolyze this substrate several times slower than
      acetylthiocholine. The values of Km in the reactions of hydrolysis of
      thionaphthylacetate for all studied cholinesterases is an order higher than for
      acetylthiocholine except cholinesterase of blood serum of fish. This value for
      the latter enzyme is practically equal.

PMID- 16100914
TI  - On the relationship between whole-body vibration exposure and spinal health risk.
AB  - A conceptual framework provides the possibility to identify factors determining
      the effects of whole-body vibration (WBV) on the spine and the internal stress
      strain relationships. Epidemiological studies were critically evaluated with
      respect to their significance for the derivation of quantitative exposure-effect
      relationships. The approach of deriving such relationships from a comparison with
      self-generated accelerations during daily activities was considered as unsuited.
      Trunk muscle activity and control with apparently identical accelerations of body
      parts during self-generated and forced motions differ widely. Simple biodynamic
      models coupled with experimental in vivo and in vitro data permitted a
      preliminary deduction of quantitative relationships between WBV and spinal health
      with the consideration of individual factors and exposure conditions. Examples of
      anatomy-based verified finite element models and their application are provided.
      Such models are considered as a very promising instrument. They can be used to
      assess quantitatively preventive measures and design. Future research needs
      concern the examination of (1) the nonlinearity of biodynamics, (2) the effects
      of WBV in x- and y-axes, (3) the strength of the spine for shear, (4) the contact
      parameters between the seat and man, (5) the significance of postures and muscle
      activity, and (6) material properties of spinal structures.

PMID- 16100915
TI  - Impedance methods (apparent mass, driving point mechanical impedance and absorbed
      power) for assessment of the biomechanical response of the seated person to whole
      body vibration.
AB  - Exposure to whole-body vibration is a risk factor for the development of low back
      pain. In order to develop a fuller understanding of the response of the seated
      person to vibration, experiments have been conducted in the laboratory
      investigating the biomechanics of the seated person. Some of these methods are
      based on the driving force and acceleration at the seat and are reported in the
      literature as apparent mass, driving point mechanical impedance or absorbed
      power. This paper introduces the background behind such impedance methods, the
      theory and application of the methods. It presents example data showing typical
      responses of the seated human to whole-body vibration in the vertical, fore-and
      aft and lateral directions. It also highlights problems that researchers might
      encounter in performing, analysing and interpreting human impedance data.

PMID- 16100916
TI  - Necessary research for standardization of subjective scaling of whole-body
      vibration.
AB  - Researches into the relationship between the physical quantity of vibration and
      the subjectively perceived quantity become important in designs for the vibration
      environment. Subjective experimental methods to obtain the relationship between
      the physical quantity of vibration and the subjectively perceived quantity are
      different depending on the design objectives which consider the human sense of
      vibration characteristic. In this review, the following are outlined: (i)
      fundamental methods for obtaining the design objectives for vibration
      environments; (ii) reported findings on the physical quantity of vibration
      environments and the human characteristics of sense vibration; and (iii) problems
      with and limits of the ISO 2631-1 standard, which defines the subjective response
      of the ride comfort in public transportation. Finally, the directions of research
      into the subjective experimental methods for obtaining design objectives in the
      vibration environment considering of the human characteristics of sense vibration
      are described.

PMID- 16100917
TI  - Application of the new ISO 2631-5 to health hazard assessment of repeated shocks
      in U.S. Army vehicles.
AB  - The U.S. Army Aeromedical Research Laboratory conducted a research program to
      develop a new methodology for health hazard assessment of tactical ground vehicle
      rides. This paper describes the new method and compares the health risk
      prediction using the new multiple shocks standard International Standards
      Organization (ISO 2631-5) to predictions by the current whole-body vibration
      (WBV) standard (ISO 2631-1). This article also describes the software tool
      developed to implement both parts of ISO 2631, as well as Army Regulation 40-10.
      The comparison shows the new standard to be more sensitive to cross-country
      terrain than other standards. Data analysis demonstrates the applicability of the
      new ISO 2631-5 standard to tactical ground vehicles, especially in the vertical
      axis.

PMID- 16100918
TI  - Effect of backrest and torso twist on the apparent mass of the seated body
      exposed to vertical vibration.
AB  - Occupational exposure to whole-body vibration is often combined with a
      requirement to perform twisting actions. This paper reports a study where the
      effect of twisting on the biomechanical response of the seated person was
      investigated. Twelve male subjects were exposed to vertical random whole-body
      vibration at 0.4 m/s2 r.m.s. Each subject sat in four different postures: 'back
      on', 'back-off', 'twist' (where subjects were required to twist the torso by 90
      degrees) and 'move' (where subjects were required to performing a moving task
      with extended arms). Similar apparent masses were measured for the 'back-on',
      'back-off' and 'twist' conditions, where a peak occurred at about 6 Hz. For the
      'move' condition, the peak in the apparent mass was attenuated indicating a
      different biomechanical response in this posture. The 6 Hz peak in fore-and-aft
      cross-axis apparent mass was eliminated in the 'move' condition. It is suggested
      that the change in biomechanical response is due to either the extended arms
      acting as a passive vibration absorber or that the twisting action interferes
      with the usual acceleration-muscle feedback system. Further work will be required
      to test these hypotheses.

PMID- 16100919
TI  - Influence of back support conditions on the apparent mass of seated occupants
      under horizontal vibration.
AB  - The response characteristics of seated human subjects exposed to fore-aft (x
      axis) and lateral (y-axis) vibration are investigated through measurements of
      dynamic interactions between the seated body and the seat pan, and the upper body
      and the seat backrest. The experiments involved: (i) three different back support
      conditions (no back support, and upper body supported against a vertical and an
      inclined backrest); (ii) three different seat pan heights (425, 390 and 350 mm);
      and three different magnitudes (0.25, 0.5 and 1.0 m/s2 rms acceleration) of band
      limited random excitations in the 0.5-10 Hz frequency range, applied
      independently along the fore-aft and lateral directions in an uncoupled manner.
      The body force responses, measured at the seat pan and the backrest along the
      direction of motion, are applied to characterize the total body apparent mass
      (APMS) reflected on the seat pan, and those of the upper body reflected on the
      backrest. Unlike the widely reported responses of seated occupants under vertical
      vibration, the responses to horizontal vibration show strong effect of excitation
      magnitude. The large displacements at lower frequencies cause considerable
      rotations of the upper body, and the knees and ankles, particularly when seated
      without a back support, which encouraged the occupants to continually shift
      larger portion of the body weight towards their feet. This together with the
      strong dependence on the excitation magnitude resulted in considerable inter
      subject variability of the data. The addition of a back support causes stiffening
      of the body to limit the low frequency rocking motion of the upper body under x
      axis motion, while considerable dynamic interactions with the backrest occur. The
      mean apparent mass (APMS) responses measured at the seat pan and the backrest
      suggest strong contributions due to the back support condition, and the direction
      and magnitude of horizontal vibration, while the role of seat height is important
      only in the vicinity of the resonant frequencies. In the absence of a back
      support, the seat pan responses predominate at a lower frequency (near 0.7 Hz)
      under both directions of motion, while two secondary peaks in the magnitude also
      occur at relatively higher frequencies. The addition of back support causes the
      seat pan response to converge mostly to a single primary peak, resulting in a
      single-degree-of-freedom like behavior, with peak occurring in the 2.7-5.4 Hz
      range under x-axis, and 0.9-2.1 Hz range under y-axis motions, depending upon the
      excitation magnitude and the back support condition. This can be attributed to
      the stiffening of the body in the presence of the constraints imposed by the
      backrest. A relaxed posture with an inclined backrest, however, causes a
      softening effect, when compared to an erect posture with a vertical backrest. The
      backrest, however, serves as another source of vibration to the seated occupant,
      which tends to cause considerably higher magnitude responses. The considerable
      magnitudes of the apparent mass response measured at the seat back under fore-aft
      motions suggest strong interactions with the backrest. Such interactions along
      the side-to-side motions, however, are relatively small. The results suggest that
      the biodynamic characterization of seated occupants exposed to horizontal
      vibration requires appropriate considerations of the interactions with the
      backrest.

PMID- 16100920
TI  - Comparison of the apparent mass during exposure to whole-body vertical vibration
      between Japanese subjects and ISO 5982 standard.
AB  - OBJECTIVE: The purpose of this study was to investigate the apparent mass of the
      sitting human body and to compare it with current experimental data and the ISO
      5982 standard impedance model. METHOD: The apparent mass of the seated human body
      in the vertical direction was measured. Twelve male subjects were exposed to
      random whole-body vibration of frequency range (1-20 Hz), with a vibration
      excitation level of 1.0 m/s2 r.m.s. The body posture was upright with no backrest
      contact. RESULTS: The obtained apparent masses were compared to the International
      Standard, (ISO 5982). The biodynamic response of the seated Japanese subjects
      peaked in the 4-6.5 Hz frequency range, which is little bit higher than the
      reported range of fundamental frequencies (4.5-5 Hz) in most other studies which
      used different experimental conditions. The outcomes show a clear difference
      between apparent mass of Japanese subjects and ISO 5982 data. CONCLUSION: It is
      not sufficient to apply the ISO 5982 standard to Japanese vehicle design or dummy
      design.

PMID- 16100921
TI  - Multi-body dynamics modelling of seated human body under exposure to whole-body
      vibration.
AB  - In vehicle systems occupational drivers might expose themselves to vibration for
      a long time. This may cause illness of the spine such as chronic lumbago or low
      back pain. Therefore, it is necessary to evaluate the influence of vibration to
      the spinal column and to make up appropriate guidelines or counter plans. In
      ISO2631-1 or ISO2631-5 assessment of vibration effects to human in the view of
      adverse-health effect was already presented. However, it is necessary to carry
      out further research to understand the effect of vibration to human body to
      examine their validity and to prepare for the future revision. This paper shows
      the detail measurement of human response to vibration, and the modelling of the
      seated human body for the assessment of the vibration risk. The vibration
      transmissibilities from the seat surface to the spinal column and to the head are
      measured during the exposure to vertical excitation. The modal paramters of
      seated subject are extracted in order to understand the dominant natural modes.
      For the evaluation of adverse-health effect the multi-body modelling of the
      spinal column is introduced. A simplified model having 10 DOFs is counstructed so
      that the transmissibilities of the model fit to those of experiment. The
      transient response analysis is illustrated when a half-sine input is applied. The
      relative displacements of vertebrae are evaluated, which can be a basis for the
      assessment of vibration risk. It is suggested that the multi-body dynamic model
      is used to evaluate the vibration effect to the spinal column for seated
      subjects.

PMID- 16100922
TI  - Recent advances in biodynamics of human hand-arm system.
AB  - The biodynamics of human hand-arm system is one of the most important foundations
      for the measurement, evaluation, and risk assessment of hand-transmitted
      vibration (HTV) exposure. This paper presents a new conceptual model relating
      factors influencing cause-effect relationships for HTV exposure, a new study
      strategy, and a comprehensive review of the recent advances in the biodynamics
      closely associated with HTV exposure. The review covers the following five
      aspects: theoretical modeling of biodynamic responses, vibration
      transmissibility, driving-point biodynamic responses, evaluation of anti
      vibration gloves, and applied forces. This review finds that some significant
      advances in each of these aspects have been achieved in the recent years. Several
      important issues and problems in the biodynamic measurement have been identified
      and resolved, which has significantly helped improve the reliability and accuracy
      of the experimental data. The results reported in recent years suggest that, from
      the point of view of biodynamics, the frequency weighting specified in ISO 5349-1
      (2001) overestimates the low frequency effect but underestimates the high
      frequency effect on the fingers and hand. The major problems, issues, and topics
      for further studies are also outlined in this paper. It is anticipated that the
      further studies of the biodynamics of the system will eventually lead to
      establishment of a robust vibration exposure theory. Although this review focuses
      on the biodynamics of the hand-arm system, the fundamental concepts and some
      methodologies reviewed in this paper may also be applicable for the study of
      whole-body vibration exposure.

PMID- 16100923
TI  - The European vibration directive.
AB  - The European Union adopted a Directive in 2002 on minimum requirements for the
      health and safety of workers exposed to vibration. This is known as the Physical
      Agents (Vibration) Directive. It builds on existing general employers' duties to
      manage risks to health and safety, and introduces exposure action and limit
      values for both hand-arm vibration and whole-body vibration, setting minimum
      standards for the control of vibration risks across Europe. New Regulations on
      Vibration at Work will be introduced in Great Britain on 6 July 2005 to implement
      the Directive. These Regulations should serve to strengthen the continuing work
      of the Health and Safety Executive (HSE) to reduce exposures to hand-arm
      vibration in British industry. Implementation of the Directive for whole-body
      vibration presents a different challenge and the HSE is currently preparing
      appropriate guidance to accompany the Regulations. This will form part of an
      holistic approach to back pain in professional drivers, setting vibration in
      context with other risk factors, particularly postural concerns and manual
      handling operations.

PMID- 16100924
TI  - The study on hand-arm vibration syndrome in China.
AB  - To review the main achievement and problems of study on hand-arm vibration
      syndrome in China. The epidemiological and clinical study indicate that HAVS was
      reported from almost provinces in China, the prevalence of VWF ranges from 2.5%
      to 82.8% in the workers with vibrating tool use. The exposure-response
      relationship between prevalence of VWF and intensity and duration of exposed to
      hand-transmitted vibration has confirmed. Diagnostic criteria of HAVS has been
      established and performed by Chinese government in 1985, and it was revised by
      government as a national standard for occupational health in 2002. The "hygienic
      standard for hand-transmitted vibration in workplace" as a national standard and
      the "methods of measurement and assessment for hand-transmitted vibration" as a
      recommend standard were published by government also. The limited value of
      exposed to hand-arm vibration was 5.0 m/s2 that is energy equivalent frequency
      weighted acceleration for a period of 4 h (ahw(4)). There are some problems in
      this field of China need to further study in the future.

PMID- 16100925
TI  - Estimation of biodynamic forces distributed on the fingers and the palm exposed
      to vibration.
AB  - The hand-tool coupling force in the operation of a vibrating tool is generally
      composed of applied force (AF) and biodynamic force (BF). There is wide interest
      in quantifying the coupling force. The objectives of this study are to develop an
      effective method for estimating the BF and to investigate its fundamental
      characteristics. Using the biodynamic response of the hand-arm system, such as
      apparent mass or mechanical impedance, and the acceleration that can be measured
      on vibrating tools, this study proposed an indirect method for the BF estimation.
      The BFs distributed on the fingers and the palm of the hand along the forearm
      direction (z(h)-axis) in the operations of eighteen types of tool were estimated
      and used to identify the distributed BF characteristics. The results indicate
      that the BFs depend on both the tool vibration spectrum and the biodynamic
      properties of the hand-arm system. The dominant BF frequency component is usually
      at the same frequency as the dominant vibration frequency of each tool. The BF
      distributed on the palm (2-98 N) is much higher than that distributed on the
      fingers (1-30 N) at frequencies less than 100 Hz, but these biodynamic forces (2
      22 N) are comparable at higher frequencies. The palm BF on several tools with
      relatively low dominant frequencies (< or = 40 Hz), especially in the resonant
      frequency range (16-40 Hz), is comparable with the applied palm force (50-100 N).
      Since the resonant frequency of the palm BF is also in the range of the dominant
      vibration frequencies of many percussive tools, the palm BF may be related to the
      disorders in the wrist-arm system. The BF on the fingers is likely to be closely
      related to the dynamic stresses and deformations in the fingers and it may thus
      be used to quantify the finger vibration exposure.

PMID- 16100926
TI  - Mechanical impedance and absorbed power of hand-arm under x(h)-axis vibration and
      role of hand forces and posture.
AB  - The biodynamic responses of the hand-arm system under x(h)-axis vibration are
      investigated in terms of the driving point mechanical impedance (DPMI) and
      absorbed power in a laboratory study. For this purpose, seven healthy male
      subjects are exposed to two levels of random vibration in the 8-1,000 Hz
      frequency range, using three instrumented cylindrical handles of different
      diameters (30, 40 and 50 mm), and different combinations of grip (10, 30 and 50
      N) and push (0, 25 and 50 N) forces. The experiments involve grasping the handle
      while adopting two different postures, involving elbow flexion of 90 degrees and
      180 degrees, with wrist in the neutral position for both postures. The analyses
      of the results revealed peak DPMI magnitude and absorbed power responses near 25
      Hz and 150 Hz, for majority of the test conditions considered. The frequency
      corresponding to the peak response increased with increasing hand forces. Unlike
      the absorbed power, the DPMI response was mostly observed to be insensitive to
      variations in the excitation magnitude. The handle diameter revealed obvious
      effects on the DPMI magnitude, specifically at frequencies above 250 Hz, which
      was not evident in the absorbed power due to relatively low velocity at higher
      frequencies. The influence of hand forces was also evident on the DPMI magnitude
      response particularly at frequencies. above 100 Hz, while the effect of hand-arm
      posture on the DPMI magnitude was nearly negligible. The magnitude of power
      absorbed within the hand and arm was observed to be strongly dependent upon the
      excitation level over the entire frequency range, while the influence of hand-arm
      posture on the total absorbed power was observed to be important. The effect of
      variations in the hand forces on the absorbed power was relatively small for the
      bent elbow posture, while an increase in either the grip or the push force
      coupled with the extended arm posture resulted in considerably higher energy
      absorption. The results suggested that the handle size, hand-arm posture and hand
      forces, produce coupled effect on the biodynamic response of the hand-arm system.

PMID- 16100927
TI  - New frequency weighting of hand-arm vibration.
AB  - A new frequency weighting method to assess hand-arm vibration exposure is
      proposed in this paper. The influence of frequency components was first estimated
      using the method of multivariate analysis, then a simple form of the weighting
      curve was introduced. Compared with the frequency weighting in the current ISO
      5349-1 (2001), the proposed weighting can better explain the relationship between
      rates of symptoms and vibration exposure among vibrating tool users. Although
      this new weighting is derived from limited data, it suggests that the current
      weighting in ISO 5349-1 should be changed to give more weight to the high
      frequency range and less weight to the low frequency range.

PMID- 16100928
TI  - Frequency weightings based on biodynamics of fingers-hand-arm system.
AB  - The frequency weighting for assessing hand-transmitted vibration exposure is
      critical to obtaining a true dose-response relationship. Any valid weighting must
      have a solid theoretical foundation. The objectives of this study are to examine
      the biodynamic foundation for assessing the vibration exposure and to develop a
      set of biodynamic methods to formulate the frequency weightings for different
      anatomical locations of the fingers-hand-arm system. The vibration
      transmissibility measured on the fingers, hand, wrist, elbow, shoulder, and head
      was used to define the transmitted acceleration-based (TAB) frequency weighting.
      The apparent masses measured at the fingers and the palm of the hand were used to
      construct the biodynamic force-based (BFB) weightings. These weightings were
      compared with the ISO weighting specified in ISO 5349-1 (2001). The results of
      this study suggest that the frequency weightings for the vibration-induced
      problems at different anatomical locations of the hand-arm system can be
      basically divided into three groups: (a) the weighting for the fingers and hand,
      (b) the weighting for the wrist, elbow, and shoulder, and (c) the weighting for
      the head. The ISO weighting is highly correlated with the weighting for the
      second group but not with the first and third groups. The TAB and BFB finger
      weightings are quite different at frequencies lower than 100 Hz, but they show
      similar trends at higher frequencies. Both TAB and BFB finger weightings at
      frequencies higher than 20 Hz are greater than the ISO weighting.

PMID- 16100929
TI  - Diagnostic criteria and staging of hand-arm vibration syndrome in the United
      Kingdom.
AB  - In the United Kingdom the diagnosis of Hand-arm Vibration Syndrome varies
      depending on the purpose of that diagnosis. The criteria differ in three
      situations. More than 100,000 miners and ex-miners with claims for HAVS have been
      examined using a Medical Assessment Process which included the use of
      standardised tests. This contract is unique but it has had significant effects on
      the two other processes. The Industrial Injuries Disablement Benefit Scheme
      provides a benefit that can be paid to an employed earner because of an accident
      or Prescribed Disease. New recommendations have been published to remove the
      anomalies in the present format for assessing HAVS. If implemented the new scheme
      will recognise the Stockholm Workshop Scales and workers with neurological
      problems will also be compensated. The Health and Safety Executive will issue new
      guidance in the near future on the hazards of hand-arm vibration. Health
      surveillance in the workplace will be fundamental and the HSE propose a tiered
      approach with levels 1 to 5. Specialist occupational nurses and doctors with
      training in the diagnosis and assessment of HAVS will be needed for levels 3 and
      4. Only at this level may a diagnosis of HAVS be made. The Medical Assessment
      Process has demonstrated that it is possible to examine a large number of
      claimants in a standardised manner. The IIAC and HSE recommendations contain very
      important improvements on the existing positions in the UK and it must be hoped
      that they will be implemented in the near future.

PMID- 16100930
TI  - Measurements of vibrotactile perception thresholds at the fingertips in Poland.
AB  - OBJECTIVES: The measurement of vibrotactile perception thresholds (VPTs) at
      fingertips in workers belongs in Poland among obligatory methods used to diagnose
      hand-arm vibration syndrome. The aim of the study was to compare vibrotactile
      perception threshold (VPT) values for healthy subjects using two different types
      of measuring equipment, i.e. a system designed according to the requirements of
      the ISO 13091-1 standard and a system that had so far been in use in Poland.
      MATERIALS AND METHODS: 59 men and 22 women aged on average 40.4 years old
      participated in the study. The VPT measurements were carried out using a new
      pallesthesiometer P8 (EMSON-MAT, Poland), developed according to the ISO 13091-1
      standard and a vibrotactile meter MCW 2K that had so far been used in Poland.
      Measurements were taken for the index, middle and ring fingers of both hands
      using the frequencies of 4, 25, 31.5, 63, 125, 250, 400 and 500 Hz for the ISO
      method and 63, 125, 250, 400 and 500 Hz for the Polish method. RESULTS: The mean
      vibrotactile perception threshold values determined with the ISO 13091-1 method
      were significantly higher in comparison with the values obtained when the method
      used in Poland was employed. The differences between vibrotactile threshold
      levels were almost the same at the compared frequencies. CONCLUSIONS: The results
      of the VPT measurements obtained employing the standard method adopted in Poland
      may be used in further diagnostic examinations carried out with the ISO 13091-1
      method only if an appropriate correction value is calculated in order to
      determine the difference in the VPT levels at a selected frequency.

PMID- 16100931
TI  - Impaired manual dexterity and neuromuscular dysfunction in patients with hand-arm
      vibration syndrome.
AB  - Manual dexterity and hand functional difficulties in daily life in hand-arm
      vibration syndrome (HAVS) were investigated in 29 male patients with HAVS and 30
      male controls without occupational exposure to hand-arm vibration. Manual
      dexterity was assessed by measuring the performance time of picking up and
      transferring 30 red beans, one by one, from one plate to another. Vibrotactile
      perception thresholds at 125 Hz and grip strength were also examined. Hand
      functional difficulties in daily life were surveyed with a questionnaire. The
      HAVS patients had an increased vibrotactile threshold, decreased grip strength,
      and low performance in transferring beans. Low performances with transfer times
      over 53 s (2SD from the mean in the controls) were found in 66% of the HAVS
      patients and 3% of the controls. Bean transfer times in the patients were
      correlated with an increasing vibrotactile threshold and decreasing grip
      strength. The transfer times of the patients were also associated with hand
      functional difficulties such as picking up coins, turning the pages of a
      newspaper, buttoning clothes, and pouring from a teapot. The patients with a
      prolonged transfer time over 60 s (3SD from the mean in the controls) were most
      likely to have hand functional difficulties. The present findings suggest that
      measurement of the bean transfer time will serve to assess manual dexterity among
      HAVS patients, and that impaired manual dexterity in patients may be associated
      with impaired sensory feedback and muscular dysfunction in the fingers and hands.

PMID- 16100932
TI  - Preliminary study on the assessment of peripheral vascular response to cold
      provocation in workers exposed to hand-arm vibration using laser Doppler
      perfusion imager.
AB  - Measurements of changes in finger skin blood flow with laser Doppler perfusion
      imaging (LDPI) in response to cold provocation test (10 degrees C, 10 min) were
      performed in 12 men suffering from vibration induced white finger (VWF) and 13
      exposed controls. The mean perfusion values in both groups reduced markedly as a
      result of immersion of the hand in cold water. In the controls, however, the mean
      value increased gradually until the end of the cold provocation, while that in
      the VWF subjects remained at the lowest level. After removal of the hand from the
      cold water, the skin blood perfusion in the controls recovered rapidly and nearly
      reached the baseline value. In the VWF subjects, it had a slight increase
      immediately following the cold immersion but no tendency to rise as the time span
      increased. Analysis of covariance controlling for possible confounders revealed
      that the VWF subjects had significantly lower perfusion values compared to the
      controls in the last several minutes of the cold provocation and the following
      recovery. These findings suggest that the LDPI technique enables visualizing and
      quantifying the peripheral vascular effects of cold water immersion on the finger
      skin blood perfusion and thus has the potential of providing more detailed and
      a&curate information that may help detect the peripheral circulatory impairment
      in the fingers of vibration-exposed workers.

PMID- 16100933
TI  - Evaluation of antivibration glove test protocols associated with the revision of
      ISO 10819.
AB  - Effects of modifying the palm adapter geometry on ISO 10819 antivibration glove
      test results were investigated. 30 rigid acrylic adapters were designed,
      fabricated, and evaluated. The length of the adapters that met ISO 10819
      requirements covered 70-80% of the width of the palm. The upper curvatures of the
      adaptors were greater than or equal to the radius specified in ISO 10819:1996.
      Glove vibration transmissibility tests were conducted using a constant velocity
      vibration input with a value of 0.01 m/s in each third octave frequency band from
      16-1,600 Hz (F spectrum). Glove vibration transmissibility results obtained using
      the M (16-400 Hz) and H (100-1,600 Hz) spectra specified in ISO 10819:1996 were
      compared to similar results using the constant velocity spectrum. The results
      obtained from the constant velocity spectrum, when divided into the M and H
      frequency ranges, were nearly the same as those obtained from the ISO 10819 M and
      H spectra. Test subject training was required to ensure reliable glove vibration
      transmissibility results. The measured transmissibility values obtained with the
      M, H, and F spectra were all higher at the beginning of the test program. The
      transmissibility values decreased and approached lower limiting values as the
      test subjects became more experienced.

PMID- 16100934
TI  - Combined effects of noise and mixed solvents exposure on the hearing function
      among workers in the aviation industry.
AB  - This study aims to evaluate the effect of occupational exposure to noise and
      organic solvents on hearing loss in the aviation industry. The study population
      comprised 542 male workers, who worked in avionics jobs in Kimhae, Korea, who
      kept records of work environment evaluations and medical examinations. The
      Cumulative Exposure Index (CEI) was constructed to assess the lifetime cumulative
      exposure of the workers, and pure tone audiometry (PTA) data of the workers from
      their biannual medical surveillance was used to assess hearing loss. The
      prevalence of hearing loss found in the group exposed to noise and mixed solvents
      simultaneously (54.9%) was higher than those in the other groups (6.0% in the
      unexposed, 17.1% in the noise-only, and 27.8 % in the exposed to only a solvents
      mixture). The relative risks, adjusted for age, were estimated to be 4.3 (95 % CI
      1.7-10.8) for the noise-only group, 8.1 (95% CI 2.0-32.5) for the noise and
      solvents group, and 2.6 (95 % CI 0.6-10.3) for the solvents-mixture group. These
      suggest that chronic exposure to mixed solvents had a toxic effect on the
      auditory system. This raises the issue of whether hearing conservation
      regulations should be applied to all workers exposed to solvents.

PMID- 16100935
TI  - Direct effect of CoC12 and NiCl2 on citrate uptake by the rat renal brush border
      membrane.
AB  - Co and Ni are essential but relatively rare elements as to organisms. In the
      mammalian membrane, these metals are transported by the same carrier proteins.
      The aim of this study was to investigate the direct effects of CoCl2 and NiCl2 on
      citrate uptake by rat renal brush border membrane vesicles (BBMV). BBMV were
      prepared by the divalent cation precipitation methods, and citrate uptake was
      measured by the Millipore rapid membrane filtration technique. The time course of
      citrate uptake during 120-min of incubation with 1 mM CoCl2 and NiCl2 showed a
      rapid significant inhibition at the early phase and a slight recover at the late
      phase. Incubation for 1 min of BBMV with 1, 5 and 25 mM CoCl2 and NiCl2,
      respectively, significantly inhibited citrate uptake in a concentration-dependent
      manner compared with that of 0 mM. We discuss these findings from the point of
      view that Co and Ni are located in Group VIII of the periodic table.

PMID- 16100936
TI  - A study on the relationship between subjective unpleasantness and body surface
      vibrations induced by high-level low-frequency pure tones.
AB  - Human body surface vibrations induced by high-level low-frequency pure tones were
      measured at the chest and the abdomen. At the same time, the subject rated the
      unpleasantness that he had just perceived during the exposure to low-frequency
      noise stimulus. Examining the relationship between the measured vibration and the
      rating score of the unpleasantness revealed that the unpleasantness was in close
      correlation with the vibration acceleration level (VAL) of the vibration
      measured. Taking previous results into account, this finding suggests that noise
      induced vibrations primarily induce vibratory sensations and through the
      vibratory sensation or together with some other factors, secondarily contribute
      to the unpleasantness. The present results suggest that in evaluating high-level
      low-frequency noise, the effect of vibration should be taken into account.

PMID- 16100937
TI  - Longitudinal study to explore chronic neuropsychologic effects on solvent exposed
      workers.
AB  - AIM: The aim of the study was to examine possible neurotoxic effects on the
      central nervous system (CNS) in relation to a chronic solvent exposure at the
      workplace. METHOD: The collective included 127 workers exposed to solvent
      mixtures, such as spray painters and printers. They were examined twice by means
      of a physical examination, neuropsychological testbattery, biological and air
      monitoring. RESULTS: Major component of the solvents were white spirits in
      concentrations up to 127 ppm in air and 2,666 microg/l in blood. Single
      substances were mainly toluene and xylenes in concentrations below current
      threshold values at the workplace. During the 2 yr interval, the concentrations
      of solvents decreased, and no significant associations between the
      neuropsychological tests and the solvent exposure were found. Regarding the whole
      working history of each participant, we found a significant reduction on
      information processing velocity and performance in the trailmaking test, as well
      as more complaints of workers with higher solvent exposure in the past.
      CONCLUSIONS: A slight increase of subjective complaints and a deteriorated power
      of concentration seems to be associated with chronic solvent exposure.

PMID- 16100938
TI  - Thirteen-week oral toxicity study of 1,4-dichloro-2-nitrobenzene in rats and
      mice.
AB  - Subchronic toxicity of 1,4-dichloro-2-nitrobenzene (DCNB) was examined by feeding
      F344 rats and BDF mice of both sexes a diet containing 1,481, 2,222, 3,333, 5,000
      or 7,500 ppm DCNB (w/w) for 13 wk. Oral administration of DCNB in feed to rats
      and mice retarded growth rates and induced subchronic toxicity affecting the
      liver, kidney, testes and blood. Liver and kidney were most responsive to DCNB.
      BMDL10 values for relative liver weight were 12.0 and 22.6 mg/kg/d for male and
      female rats, respectively, and 88.7 and 94.4 mg/kg/d for male and female mice,
      respectively. Increased liver weights and centrilobular hypertrophy of
      hepatocytes were observed in the DCNB-fed rats and mice of both sexes. Both
      increased serum activities of AST and ALT and liver necrosis occurred in the DCNB
      fed mice. Increased incidences of hyaline droplets and granular casts in the
      proximal renal tubules were observed only in the DCNB-fed male rats, indicating
      alpha2v-globulin nephropathy. Eosinophilic droplets in the renal tubular cells
      and increased BUN concentrations occurred in the DCNB-fed female rats. DCNB
      induced testicular and hematologic changes were noted in rats and mice. On the
      basis of these results, the highest dose level for the 2-yr bioassay study of
      rodent carcinogenicity was determined to be 2,000 ppm.

PMID- 16100939
TI  - Ten-year follow-up of blood lead levels with medical removal protection of
      shipyard workers.
AB  - This cases report compared the short-term changes of BLL with medical removal
      intervention and follow-up the long-term changes of BLL afterward. During a
      physical examination in October 1992, a 44-year old shipyard welder was
      discovered to have a blood lead level (BLL) of 54.1 microg/dl. It was recommended
      that the shipyard remove this worker from his workplace. In 1993 the BLLs checked
      for this worker were 36.7 microg/dl in March and 32.0 microg/dl in April. After
      six months of medical removal, he returned to initial welding work. In 2002, we
      collected two blood samples from this worker for analysis in May and October. The
      results were 30.4 microg/dl and 31.6 microg/dl, respectively. Meanwhile, two
      other welding workers (case 2 and case 3) with BLLs over 40 microg/dl in the
      survey conducted at the same shipyard in 1992. It took 4 yr to let BLLs downed to
      less than 40 microg/dl. However, after the blood lead concentration drops to
      below 40 microg/dl, 10 yr long-term observation indicates that BLLs reduction
      level off and do not continue to go down in these three cases.

PMID- 16100940
TI  - Genetic testing for inherited breast cancer risk in African Americans.
AB  - As genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations is increasingly
      integrated into the clinical management of high-risk women, it will be important
      to understand barriers and motivations for genetic counseling among women from
      underserved minority groups to ensure equitable access to these services.
      Therefore, the purpose of this review was to synthesize literature on knowledge
      and attitudes about genetic counseling and testing for inherited breast cancer
      risk in African Americans. We also review studies that evaluated genetic testing
      intentions in this population. We conducted a search of the PubMed database to
      identify studies related to BRCA1/2 testing in African Americans that were
      published between 1995 and 2003. Overall, studies have evaluated ethnic
      differences in knowledge and attitudes about genetic testing or have compared
      African American and Caucasian women in terms of genetic testing intentions.
      These studies have shown that knowledge about breast cancer genetics and exposure
      to information about the availability of testing is low among African Americans,
      whereas expectations about the benefits of genetic testing are endorsed highly.
      However, much less is known about the psychological and behavioral impact of
      genetic testing for BRCA1/2 mutations in African Americans. Additional research
      is needed to understand barriers and motivations for participating in genetic
      testing for inherited cancer risk in African Americans. The lack of studies on
      psychological functioning, cancer surveillance, and preventive behaviors
      following testing is a significant void; however, for these studies to be
      conducted, greater access to genetic counseling and testing in African Americans
      will be needed.

PMID- 16100941
TI  - Gefitinib in patients with advanced non-small cell lung cancer (NSCLC): the
      expanded access protocol experience at the University of Pennsylvania.
AB  - Gefitinib (Iressa; AstraZeneca Pharmaceuticals, Wilmington, DE) is an oral
      epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) with
      favorable toxicity and antitumor activity in pretreated patients with non-small
      cell lung cancer (NSCLC). The purpose of this study was to evaluate the toxicity
      and efficacy of gefitinib in patients with advanced NSCLC treated at our
      institution as part of an expanded access protocol; 112 patients with advanced
      NSCLC were entered. All patients had failed at least one previous chemotherapy
      regimen, or were not suitable for any systemic chemotherapy because of poor
      performance status (PS), or were ineligible for other clinical trials. Therapy
      consisted of gefitinib 250 mg orally once daily; 10.5% (95% CI 5.3-17.9%) of
      patients achieved partial/minimal response (PR/MR) and 29.5% (95% CI 21.0-39.2%)
      had stable disease (SD), resulting in a disease control rate (PR/MR+SD) of 40%
      (95% CI 31-50%). The median duration of treatment for all patients was 12 weeks
      (range 2-116 weeks) and for patients achieving disease control 28 weeks (range 8
      116). Nine patients received gefitinib for more than 1 year. Median survival was
      30 weeks. Symptoms were improved in 36% of evaluable patients, and 64% of
      patients who achieved disease control experienced improvement of their disease
      related symptoms. Adverse events were generally mild and consisted mostly of skin
      rash (48%) and diarrhea (38%). A statistically significant association was
      observed between disease control and skin rash (p = < 0.001), nonsmoking status
      (p = 0.048), and symptom improvement (p = 0.001). The disease control rate was
      not statistically associated with histology, PS, gender, or number of prior
      treatments. In addition, longer survival was significantly associated with skin
      rash (p = < 0.001) and symptom improvement (p = < 0.001). Gefitinib demonstrated
      relevant clinical activity and a favorable toxicity profile in pretreated
      patients with advanced NSCLC. The development of toxicity was associated with a
      favorable response. In addition, a history of never having smoked seems to
      predict a higher efficacy of gefitinib.

PMID- 16100942
TI  - A phase II study of biochemotherapy for advanced melanoma incorporating
      temozolomide, decrescendo interleukin-2 and GM-CSF.
AB  - Metastatic malignant melanoma remains a very difficult disease to treat. Previous
      phase II studies using biochemotherapy (combination of platinum-containing
      chemotherapy with IL-2 and IFNalpha) have shown response rates of about 50%.
      However, a site of frequent relapse is in the central nervous system (CNS).
      Temozolomide is an oral alkylating agent that has equivalent activity to
      dacarbazine, but it has the advantage of CNS penetration. We report the results
      of a phase II study using a novel biochemotherapy regimen containing
      temozolomide, cisplatin, decrescendo IL-2, IFNalpha, and GM-CSF in the treatment
      of stage IV melanoma. Seventy-one patients with histologically confirmed
      metastatic melanoma were enrolled between June 1998 and October 1999. Prior
      chemotherapy or IL-2 was not permitted. The median age was 54 years (range 22
      72). Twenty-one patients (30%) had a history of treated brain metastases.
      Patients received temozolomide 150 mg/m2 orally days 1-5, cisplatin 30 mg/m2 IV
      days 1-3, IFNalpha 5 MU/m2 SQ on days 1-5, and IL-2 was administered in a
      decrescendo fashion according to the following schedule: day 1: 18 MU/m2
      continuous IV infusion over 6 hours; day 2: 18 MU/m2 continuous IV infusion over
      12 hours; day 3: 9 MU/m2 subcutaneously q12 hours; day 4: 4.5 MU/m2
      subcutaneously x 1. Patients were also given GM-CSF 250 microg subcutaneously
      days 6-25. The cycles were repeated every 4 weeks. Partial responses were seen in
      10 of the 71 patients (14%) with a median duration of response of 9.4 months.
      There were no complete responses. The median survival for all patients was 8.6
      months. Further studies of this novel biochemotherapy regimen are not indicated.
      Other schedules that incorporate temozolomide and/or GM-CSF and further studies
      to define the optimal method of delivering IL-2 should be pursued.

PMID- 16100943
TI  - Effects of exogenous wild-type P16 gene transfection on the expression of cell
      cycle-related proteins in bladder cancer cell line.
AB  - Cell cycle regulatory proteins are important indicators in determining
      progression through the cell cycle. Recent experimental evidence shows that
      active Cdk4-Cyclin D1 complexes help cells to pass through the R point, a point
      of no return, after which the cells become committed to a new round of
      replication. It is widely known that P16INK4a can arrest cells in the G1 phase,
      but how the expression of exogenous P16INK4 gene can affect the activity of Cdk4
      Cyclin D1 remains unclear. In this study, using exogenous wild-type P16 gene,
      antibodies for P16, Cdk4, Cyclin D1 and Rb proteins, and primers for these genes,
      we examined the expression of exogenous wild-type P16 gene and the changes of
      cell cycle regulatory genes (Cdk4, Cyclin D1, and Rb) in human bladder cancer
      cells. The cell cycle analysis revealed that the proliferation of P16 gene
      transfected cancer cells was inhibited after the transfection of exogenous wild
      P16 gene. The immunocytochemical results indicated that after the transfection of
      exogenous wild-type P16 gene, the expression of Cdk4, Cyclin D1, and Rb were
      negative in the nuclei, whereas the expression of P16 significantly increased in
      the nuclei and the cytoplasm. The RT-PCR results showed that the transcription of
      P16 gene increased significantly after the transfection, whereas the
      transcription of Cdk4, Cyclin D1, and Rb decreased. Our results suggest that the
      transfection of exogenous wild P16 gene induces the bladder cancer cells arrested
      in G0/G1 phase, and the increasing expression of P16 inhibits the expression of
      Cdk4, Cyclin D1, and Rb in nuclei. As a consequence, exogenous P16 has negative
      effects on the malignant proliferation of the bladder cancer cells, and it may be
      considered as target for potential anticancer drugs.

PMID- 16100944
TI  - Antitumor activation of peritoneal macrophages by thymosin alpha-1.
AB  - It was been previously reported that thyalpha1 can be used to activate monocytes,
      BMDM and TAM. However, the effect of thyalpha1 on other tissue macrophages has
      not been investigated. Moreover, there is no report about the use of thyalpha1
      treated macrophages in adoptive immunotherapy of cancer. In view of these
      observations in the present study, we checked the response of various tissue
      macrophages to thyalpha1 for activation. Tissue macrophages showed differential
      response to thyalpha1; moreover, adoptive transfer of peritoneal macrophages
      treated with thyalpha1 to mice bearing spontaneous T-cell lymphoma designated as
      Dalton's lymphoma (DL) resulted in the prolongation of the survival time of tumor
      bearing mice. The mechanism of macrophage therapy-dependent tumor regression was
      enhanced antitumor activity of macrophages in response to thyalpha1 treatment via
      their production of macrophage-activating cytokines that act in autocrine manner.
      These results will help in the development of immunotherapy against tumor based
      on activation of macrophage with thyalpha1.

PMID- 16100945
TI  - A review of evidence-based treatment of stage IIB to stage IV melanoma.

PMID- 16100946
TI  - Carcinoembryonic antigen in the staging and follow-up of patients with colorectal
      cancer.
AB  - CEA is a complex glycoprotein produced by 90% of colorectal cancers and
      contributes to the malignant characteristics of a tumor. It can be measured in
      serum quantitatively, and its level in plasma can be useful as a marker of
      disease. Because of its lack of sensitivity in the early stages of colorectal
      cancer, CEA measurement is an unsuitable modality for population screening. An
      elevated preoperative CEA is a poor prognostic sign and correlates with reduced
      overall survival after surgical resection of colorectal carcinoma. A failure of
      the CEA to return to normal levels after surgical resection is indicative of
      inadequate resection of occult systemic disease. Frequent monitoring of CEA
      postoperatively may allow identification of patients with metastatic disease for
      whom surgical resection or other localized therapy might be potentially
      beneficial. To identify this group, serial CEA measurement appears to be more
      effective than clinical evaluation or any other diagnostic modality, although its
      sensitivity for detecting recurrent disease is not as high for locoregional or
      pulmonary metastases as it is for liver metastases. Several studies have shown
      that a small percentage of patients followed postoperatively with CEA monitoring
      and who undergo CEA-directed salvage surgery for metastatic disease will be alive
      and disease-free 5 years after surgery. Furthermore, CEA levels after salvage
      surgery do appear to predict survival in patients undergoing resection of liver
      or pulmonary metastases. However, several authors argue that CEA surveillance is
      not cost-effective in terms of lives saved. In support of this argument, there is
      no clear difference in survival after resection of metastatic disease with
      curative intent between patients in whom the second-look surgery was performed on
      the basis of elevated CEA levels and those with other laboratory or imaging
      abnormalities. There is also no clear consensus on the frequency or duration of
      CEA monitoring, although the ASCO guidelines currently recommend every 2-3 months
      for at least 2 years after diagnosis. In the follow-up of patients undergoing
      palliative therapy, the CEA level correlates well with response, and CEA is
      indicative of not only response but may also identify patients with stable
      disease for whom there is also a demonstrated benefit in survival and symptom
      relief with combination chemotherapy. More recently, scintigraphic imaging after
      administration of radiolabeled antibodies afforded an important radionuclide
      technique that adds clinically significant information in assessing the extent
      and location of disease in patients with colorectal cancer above and beyond or
      complementary to conventional imaging modalities. Immunotherapy based on CEA is a
      rapidly advancing area of clinical research demonstrating antibody and T-cell
      responses.

PMID- 16100947
TI  - Evidence-based recommendations for local-regional control of gastric cancer.

PMID- 16100948
TI  - Current concepts and controversies in the treatment of parenchymal brain
      metastases: improved outcomes with aggressive management.
AB  - The multimodality management of brain metastases has undergone significant
      refinement in the last decade. Although brain metastases remain a significant
      source of morbidity and mortality for many cancer patients, aggresive management
      has led to pronounced gains in neurological functioning, disease free survival
      and overall survival compared to standard treatment regimens consisting of only
      whole brain radiation therapy. Representative studies reviewing the role of
      aggressive management approaches including surgical resection with or without
      whole brain radiation therapy or non-surgical approaches employing stereotactic
      radiosurgery alone or in combination with whole brain radiation therapy are
      highlighted. Additionally, the emerging role of systemic agents showing distinct
      clinical activity in patients with brain metastases are also discussed. As we
      continue to gain advances in systemic therapies for metastatic disease, local
      control of brain metastases in these patients is likely to become more critical
      in improving survival and quality of life, thereby calling for a more aggressive
      multi-modal approach to this population of patients.

PMID- 16100949
TI  - "Marking improvements in the treatment of gastric cancer--where do we go from
      here?".

PMID- 16100950
TI  - Protein folding in the cell: molecular chaperones pave the way.
AB  - In vitro, many unfolded polypeptides are able to fold to the native state
      spontaneously, indicating that the amino acid sequence of a protein contains all
      the information necessary to specify its three-dimensional conformation. It had
      been assumed that protein folding in vivo also generally occurs in a spontaneous
      process. This view has changed only recently due to the discovery of a number of
      proteins, now commonly called 'molecular chaperones', which are essential for
      cellular protein folding and occur ubiquitously in eubacteria, archaebacteria and
      in eukaryotic cells.

PMID- 16100951
TI  - Recognition between a bacterial ribonuclease, barnase, and its natural inhibitor,
      barstar.
AB  - BACKGROUND: Protein-protein recognition is fundamental to most biological
      processes. The information we have so far on the interfaces between proteins
      comes largely from several protease-inhibitor and antigen-antibody complexes.
      Barnase, a bacterial ribonuclease, and barstar, its natural inhibitor, form a
      tight complex which provides a good model for the study and design of protein
      protein non-covalent interactions. RESULTS: Here we report the structure of a
      complex between barnase and a fully functional mutant of barstar determined by X
      ray analysis. Barstar is composed of three parallel alpha-helices stacked against
      a three-stranded parallel, beta-sheet, and sterically blocks the active site of
      the enzyme with an alpha-helix and adjacent loop. The buried surface in the
      interface between the two molecules totals 1630 A2. The barnase-barstar complex
      is predominantly stabilized by charge interactions involving positive charges in
      the active site of the enzyme. Asp39 of barstar binds to the phosphate-binding
      site of barnase, mimicking enzyme-substrate interactions. CONCLUSION: The
      phosphate-binding site of the enzyme is the anchor point for inhibitor binding.
      We propose that this is also likely to be the case for other ribonuclease
      inhibitors.

PMID- 16100952
TI  - Determination of the NMR solution structure of the Hoechst 33258-d(GTGGAATTCCAC)2
      complex and comparison with the X-ray crystal structure.
AB  - BACKGROUND: The chromosomal stain, Hoechst 33258, binds to the minor groove of
      the DNA double helix and specifically recognizes a run of four A-T base pairs.
      Extensive biochemical and biophysical studies have been aimed at understanding
      the binding of the dye to DNA at the atomic level. Among these studies there have
      been several crystal structure determinations and some preliminary structural
      studies by NMR. RESULTS: On the basis of our own previously reported NMR data, we
      have now determined the three-dimensional solution structure of the 1:1 complex
      between Hoechst 33258 and the self-complementary DNA duplex d(GTGGAATTCCAC)2. Two
      coexisting families of con formers, which exhibit differences in their
      intermolecular hydrogen bonding pattern, were found and the two terminal rings of
      the dye displayed greater internal mobility than the rest of the molecule.
      CONCLUSIONS: The observed multiple ligand-binding modes in the complex between
      Hoechst 33258 and DNA and differential internal mobility along the bound ligand
      provide a novel, dynamic picture of the specific inter actions between ligands
      that bind in the minor groove and DNA. The dynamic state revealed by these
      studies may account for some of the significant differences previously observed
      between different crystal structures of Hoechst 33258 complexed with a different
      DNA duplex, d(CGCGAATTCGCG)2.

PMID- 16100953
TI  - DNA recognition by the oestrogen receptor: from solution to the crystal.
AB  - BACKGROUND: The steroid/nuclear hormone receptors are a large family of conserved
      ligand-activated transcription factors that regulate gene expression through
      binding to response elements upstream of their target genes. Most members of this
      family bind to DNA as homodimers or heterodimers and recognize the sequence,
      spacing and orientation of the two half-sites of their response elements. The
      recognition and discrimination of the sequence and arrangements of these half
      sites are mediated primarily by a highly conserved DNA-binding domain. RESULTS:
      Here we describe the DNA-binding properties of the isolated DNA-binding domain of
      the oestrogen receptor, the ERDBD, and its refined NMR structure. This domain is
      monomeric in solution, but two molecules bind cooperatively to specific DNA
      sequences; this cooperativity determines the arrangement of half-sites that is
      recognized by the ERDBD. The 10 carboxy-terminal residues and a region of 15
      residues within the domain are disordered in the solution structure, yet are
      important for DNA binding. CONCLUSION: The cooperative nature of ERDBD binding to
      DNA is important. The previously-determined X-ray structure of the ERDBD dimer
      bound to DNA shows that the 15 internal residues disordered in solution make
      contact both with DNA and with the corresponding region of the other monomer.
      These results suggest that these residues become ordered during the process of
      binding to DNA, forming the dimer interface and thus contributing to the
      cooperative interaction between monomers.

PMID- 16100954
TI  - The crystal structure of an engineered monomeric triosephosphate isomerase,
      monoTIM: the correct modelling of an eight-residue loop.
AB  - BACKGROUND: The triosephosphate isomerase (TIM) fold is found in several
      different classes of enzymes, most of which are oligomers; TIM itself always
      functions as a very tight dimer. It has recently been shown that a monomeric form
      of TIM ('monoTIM') can be constructed by replacing a 15-residue interface loop,
      loop-3, with an eight-residue fragment; modelling suggests that this should
      result in a short strain-free turn, resulting in the subsequent helix, helix-A3,
      having an additional turn at its amino terminus. RESULTS: The crystal structure
      of monoTIM shows that it retains the characteristic TIM-barrel (betaalpha)8-fold
      and that the new loop has a structure very close to that predicted. Two other
      interface loops, loop-1 and loop-4, which contain the active site residues Lys13
      and His95, respectively, show significant changes in structure in monoTIM
      compared with dimeric wild-type TIM. CONCLUSION: The observed structural
      differences between monoTIM and wild-type TIM indicate that the dimeric
      appearance of TIM determines the location and conformation of two of the four
      catalytic residues.

PMID- 16100955
TI  - A preliminary cinemicrographic study on the effect of NGF on the growth of chick
      embryonic sensory neurites in vitro.
AB  - Trypsin dissociated dorsal root ganglia of 8-day-old chick embryos were cultured
      and filmed in the presence or absence of NGF. The behaviour of neurites and their
      association with Schwann cells and fibroblasts were observed and described.
      Isolated neurons cultured in the presence or absence of NGF were filmed and
      quantitatively analysed to determine the rate of increase in length of their
      neurites. Isolated neurons growing in control medium were perfused with either
      NGF or Medium 199 to determine the effect these agents had on rate of advance of
      nerve processes. Under these particular experimental conditions NGF was shown to
      increase the rate of growth in length of embryonic neurites but no more than did
      the nutrient Medium 199.

PMID- 16100956
TI  - Fiber formation and myelinization of cultivated dissociated neurons from chicken
      dorsal root ganglia: an electron microscopic and scanning electron microscopic
      study.
AB  - Dissociated neurons from chicken embryo dorsal root ganglia were cultivated in
      Rose chambers for up to 5 weeks. Newly formed fibers appeared as single fibers or
      grouped in bundles. During the first week of cultivation microtubules and
      microfilaments were frequently observed. The diameters of the fibers increased
      progressively and a number of varicosities appeared. In some distal portions of
      fibers large vesicles could be observed. During the second week in culture
      Schwann cells were easily recognized. They appeared as both dark and light cells.
      During this period myelinization of some fibers was seen to commence. High
      glucose concentrations were not observed to influence the process of
      myelinization. Essentially the important factors were the number of cells present
      in the culture and also the presence of NGF in the medium. Schwann cells
      myelinated nerve fibers exclusively. Two types of abnormalities in myelin
      formation were recognized: one Schwann cell myelinating two fibers and one fiber
      being myelinated twice, by two Schwann cells. Concomitantly with myelinization,
      myelin degeneration was observed. Histiotypic fascicles, typical constituents of
      the outgrowth zone of cultivated intact dorsal root ganglia, bundles of fibers,
      surrounded by connective tissue, are not formed. The surface ultrastructure of
      nerve fibers, as studied by scanning EM, was seen to be covered by numerous
      spherical elements as well as by small fibers and irregular elements. The growth
      cones of fibers were void of any glial contact. Myelinization occupied individual
      isolated segments along with nerve fibers and evidenced the absence of nodes of
      Ranvier. Relationships between single elements in the dissociated culture system
      are discussed, with respect to the possibilities for analysis of some of the
      elementary mechanisms of cellular and molecular interaction responsible for the
      development of the peripheral nervous system.

PMID- 16100957
TI  - Dopamine-beta-hydroxylase activity during sympathetic reinnervation of rat iris
      in organ culture.

PMID- 16100958
TI  - A developmental study of the relationship between the protein components of rat
      CNS myelin.
AB  - The relationship between the major and minor protein components of the myelin
      sheath, and between fractions soluble and insoluble in chloroform methanol has
      been studied in rat brain between 5 and 60 days of age. The results suggest a
      continuous sequential buildup of the myelin sheath, in which while the minor
      protein components form the major proportion of early myelin their contribution
      is progressively reduced by the addition of myelin specific proteins. Chloroform
      methanol insoluble myelin is recognisable before the CMS fraction appears. The
      minor proteins are present in the brain several days before myelination and then
      appear to migrate into myelin. However, the myelin specific proteins can only be
      detected shortly before myelination. The results underline previous suggestions
      that the myelin sheath has a unique protein composition, and suggest that the
      specific components arise de novo just before they are required. They are not
      consistent with the supposition that myelin consists of glial cell membrane and
      are discussed in relation to current views on the myelination process.

PMID- 16100959
TI  - Age-dependent utilization of phenylalanine for the synthesis of neuronal and
      glial proteins.
AB  - 1. Groups of 5-, 10-, 18- and 43-day old rats were injected intracerebrally with
      a single dose of [U14C] phenylalanine and its conversion to acid-soluble
      metabolites was determined in the cerebral cortex over a period of 24 h. Although
      the most rapid utilization of [14C] phenylalanine occurred initially in the
      oldest group, by 45 min the 18-day old cortex had the lowest levels of unchanged
      [14C] phenylalanine; by 24 h [14C] phenylalanine was, in turn, lowest in the 10
      day old cortex. 2. The specific radioactivity of [14C] phenylalanine decreased
      rapidly at all ages for the first 2 h; it then continued to decrease in the two
      younger age groups while it remained virtually constant in the two older ones. 3.
      We also determined the incorporation of [14C] phenylalanine into, and the loss of
      radioactivity from, cortical, glial and neuronal proteins, isolated from animals
      injected on their 10th, 18th and 43rd day of life and followed over a period of
      two weeks. a. The proteins of the 10-day old cortex attained the highest specific
      radioactivity and were labeled at the highest rate. b. The glial proteins and
      particularly those of the 10-day old cortex were consistently more highly
      radioactive than the neuronal proteins; the rates of radioactivity decay from
      neuronal and glial proteins were parallel, however. c. The decay of the
      radioactivity followed a similar time course at all ages and for all proteins
      examined, exhibiting two phases, a rapid one extending from day 1 (day 3 in the
      18-day old cortex) to day 7 and a slower phase extending through the entire
      second week.

PMID- 16100960
TI  - Localization of antigenic determinants on bovine encephalitogenic protein:
      disease-inducing activity of fragment 44-68 in rabbits.
AB  - Region 44-68 of the basic protein of bovine central nervous system myelin is
      shown to have moderate encephalitogenic activity when rabbits are used as test
      animals. This finding is interpreted to mean that a second disease-inducing site,
      different from the decapeptide region enclosing residues 65-74 described by
      Shapira et al. (1971a) exists within region 44-89 of the encephalitogenic
      protein. On the other hand, we have been unable to induce clinical disease with
      peptide 69-89.

PMID- 16100961
TI  - Alzheimer's disease and proton magnetic resonance spectroscopy of limbic regions:
      a suggestion of a clinical-spectroscopic staging.
AB  - OBJECTIVE: To compare magnetic resonance proton spectroscopic with clinical data
      and to propose a spectroscopic staging of Alzheimer's disease (AD). METHOD:
      Subjects (n = 46), normals (12) and with AD (34), paired to age (CDR0-CDR3); AD
      diagnosis according to DSM-IV/NINCDS-ADRDA criteria; 1H-MRS with Signa Horizon LX
      GE, 1.5T; single voxel at hippocampal region/HCR and posterior cingulate
      area/PCA. RESULTS: Statistically significant decrease (p < 0.01) only of Naa/Cr-
      at HCR among the CDR0, CDR1+CDR2, and CDR3, and at PCA between CDR0 and CDR1+CDR2
      in relation to CDR3. CONCLUSION: The HCR is the first to show Naa reduction
      (CDR1). The PCA suffers later (CDR3). These values decline progressively
      according to the severity stages. Considering the disparities between the HCR and
      PCA it is possible to suggest a spectroscopic (metabolite) staging (MS) of AD, as
      follows: MS0 (-CDR0) = both normal HCR and PCA, MS1-2 (approximately CDR1-2) =
      abnormal HCR and normal PCA, and MS3 (approximately CDR3) = both abnormal HCR and
      PCA. These results make possible the early diagnosis, to follow the degenerative
      process throughout the course, and to suggest a spectroscopic staging related to
      the clinical stages of AD.

PMID- 16100962
TI  - Cross-cultural adaptation of the quality of life assessment scale on Alzheimer
      disease.
AB  - OBJECTIVE: To present the internal validation of the quality of life (QOL)
      evaluation scale for patients with Alzheimer's disease (AD) and their
      caregivers/family members, proposed by Logsdon et al. METHOD: The scale was
      adapted through translation, back translation and equivalence evaluation. The
      Portuguese version was administered to a sample of 40 patients with mild to
      moderate AD according to NINCDS ADRDA and DSM-III-R criteria, and also to their
      respective caregivers/family members. RESULTS: The reliability of the instrument
      was excellent, both in the intra and the inter-examiner test-retest. The
      correlation coefficients for the intra-examiner assessment were 0.87/0.95/0.95 (p
      < 0.001)) for the patient, family and caregiver versions, respectively. The
      correlation coefficients for the inter-examiner assessment were 0.76/0.96/0.93 (p
      < 0.001) for the patients, family and caregiver versions, respectively. The
      reliability was excellent for both the patient and the relatives' versions in
      relation to the patient's QOL (alpha = 0.81 and 0.85, respectively), and also in
      relation to the caregiver's QOL (alpha = 0.84). CONCLUSION: The adapted version
      of the instrument proved to be straightforward and brief, presenting excellent
      stability and reliability. The Portuguese version can be obtained by contacting
      the first author.

PMID- 16100963
TI  - Prevalence of cognitive and functional impairment in community-dwelling elderly:
      importance of evaluating activities of daily living.
AB  - The study aims to evaluate the prevalence of cognitive/functional impairment in
      community-dwelling elderly above 60 years of age (n = 870; m = 297, f = 573) and
      the relationship of age, gender, and functional impairment with cognitive
      impairment using Mini-Mental State Examination (MMSE) and Pfeffer Functional
      Activities Questionnaire (PFAQ). Chi-square and Student's tests were used to
      compare cognitive and functional deficits. Linear regression assessed MMSE/PFAQ
      relationship. Stratified analysis assessed confounding factors. Logistic
      regression assessed the relationship among age/gender/functional status with
      cognitive impairment (p < 0.05). Prevalence of cognitive/functional impairment
      was 19.2%. Functional and cognitive impairment are negatively correlated (Pearson
      = 0.737), despite educational level (illiterate/literate: OR = 15.60; p = 0/OR =
      16.40; p = 0). Age and gender (female) were associated with cognitive/functional
      impairment. Functional impairment is highly correlated to cognitive impairment.
      Family/health professionals may recognize functional impairment more easily than
      cognitive impairment. Thus, the use in combination of cognitive and functional
      scales is important when screening for dementia.

PMID- 16100964
TI  - Frequency of obsessive and compulsive symptoms in patients with blepharospasm and
      hemifacial spasm.
AB  - BACKGROUND: Blepharospasm (BS) is a form of central focal dystonia recently
      associated with psychiatric disorders, particularly obsessive and compulsive
      symptoms. Hemifacial spasm (HFS) represents a focal myoclonus with peripheral
      origin in the facial nerve. OBJECTIVE: To determine the frequency of obsessive
      and compulsive symptoms in patients with BS in comparison with patients with HFS.
      METHODS: 30 patients from each group (BS and HFS) followed by the botulinum toxin
      clinic at the HC-UFPR were evaluated using a structured interview based on the
      DSM-IV criteria and the Yale-Brown scale. Results were compared by the mean two
      tailed t test. RESULTS: We found obsessive or compulsive symptoms in 20 (66.6%)
      patients with BE and 21 (70%) with HFS. Yale-Brown scale scores for each group
      were higher among BS patients; however, diferences were not statisticaly
      significant. CONCLUSION: Our study did not show a significant diference in the
      comparison of the prevalence of obsessive and compulsive symptoms among patients
      with BS and HFS.

PMID- 16100965
TI  - Depression in chronic migraine: severity and clinical features.
AB  - INTRODUCTION: Chronic migraine (CM) is a common medical condition affecting 2.4%
      of the general population. Depression is one of the most frequent comorbid
      disorders in CM. METHOD: Seventy patients diagnosed with chronic migraine were
      studied. All patients evaluated filled out the Beck Depression Inventory (BDI).
      Depression severity was divided into none or minimal depression, mild, moderate,
      and severe. RESULTS: BDI ranged from 4 to 55, mean 21 +/- 10.7. Moderate or
      severe depression, were present in 58.7% of the patients. Some degree of
      depression appeared in 85.8% of patients. The BDI scores correlated with pain
      intensity (p = 0.02). Severe depression was more frequent in patients with
      comorbid fibromyalgia and in patients reporting fatigue. CONCLUSION: The BDI is
      an easy tool to access depression in CM patients. Suicide risk assessment is
      needed in CM patients. Patients with fibromyalgia and fatigue are at even higher
      risk for severe depression.

PMID- 16100966
TI  - Botulinum toxin a in the treatment of blepharospasm: a 10-year experience.
AB  - To evaluate the long-term effect of botulinum toxin type A (BTX) in the treatment
      of blepharospasm, a retrospective analysis was conducted from the patients seen
      at the Movement Disorders Clinic of the Department of Neurology, Hospital das
      Clinicas, University of Sao Paulo School of Medicine from 1993 to 2003. A total
      of 379 treatments with BTX were administered to 30 patients with blepharospasm.
      Sixty six per cent of the subjects had used oral medication for dystonia and only
      15% of them reported satisfactory response to this treatment. Ninety three per
      cent of the patients showed significant improvement after the first BTX
      injection. There was no decrement in response when compared the first and the
      last injection recorded. Adverse effects, mostly minor, developed at least once
      in 53% of patients. Six patients (20%) discontinued the treatment but there was
      no case of secondary resistance.

PMID- 16100967
TI  - Mitoxantrone in secondarily progressive multiple sclerosis: a series of 18
      patients.
AB  - Mitoxantrone hydrochloride (Novantrone) is an anthracenedione that has been used
      as one of the latest in a long line of general immunosuppresive agents studied in
      multiple sclerosis (MS). We reviewed the clinical, laboratory, neuroimaging and
      echocardiography data of 18 patients from February 2001 to March 2004 out of a
      total number of 100 patients with definite MS. Fourteen patients were women
      (77.7%) and four were men. The mean age of the patients was 41.6 +/- 10 years old
      (confidence intervals 95%: 36.4-46.7 years old). The mean duration of disease was
      10.5 +/- 6.3 years. Fourteen patients had the secondarily progressive form of MS,
      and four had the relapsing-remitting form. Mitoxantrone is an useful and
      clinically effective drug in MS and its major limitation is the potencial
      cardiotoxicity due to cumulative dose (140 mg).

PMID- 16100968
TI  - Analysis of the influence of bromazepam on cognitive performance through the
      visual evoked potential (P300).
AB  - Benzodiazepines have been used in the pharmacological treatment of anxiety for
      over four decades. However, very few studies have combined bromazepam and event
      related potentials (ERP). The present study aimed at investigating the modulatory
      effects of this drug on brain dynamics. Specifically, the effects of bromazepam
      (3 mg) on the P300 component of the ERP were tested in a double-blind experiment.
      The sample, consisting of 15 healthy subjects (7 male and 8 female), was
      submitted to a visual discrimination task, which employed the "oddball" paradigm.
      Electrophysiological (P300) and behavioral measures (stroop, digit span, and
      reaction time) were analyzed across three experimental conditions: placebo 1,
      placebo 2, and bromazepam. Results suggest that the effects of bromazepam (3 mg)
      on cognitive processes are not apparent. In spite of what seems irrefutable in
      current literature, bromazepam did not produce evident effects on the behavioral
      and electrophysiological variables analyzed.

PMID- 16100969
TI  - Limb-girdle muscular dystrophy: an immunohistochemical diagnostic approach.
AB  - The limb-girdle muscle dystrophy (LGMD) represents a heterogeneous group of
      muscular diseases with dominant and recessive inheritance, individualized by gene
      mutation. A group of 56 patients, 32 males and 24 females, with suggestive LGMD
      diagnosis were submitted to clinical evaluation, serum muscle enzymes,
      electromyography, muscle biopsy, and the immunoidentification (ID) of
      sarcoglycans (SG) alpha, beta, gamma and delta, dysferlin and western blot for
      calpain-3. All the patients had normal ID for dystrophin (rod domain, carboxyl
      and amine terminal). The alpha-SG was normal in 42 patients, beta-SG in 28, beta
      SG in 45, deltaSG in 32, dysferlin in 37 and calpain-3 in 9. There was a
      reduction in the alpha-SG in 7 patients, beta-SG in 4, gamma-SG in 2, and delta
      SG in 8. There was deficiency of alpha-SG in 7 patients, beta-SG in 6, gamma-SG
      in 9, delta-SG in 5, dysferlin in 8, and calpain-3 in 5. The patients were
      grouped according the ID as sarcoglycans deficiency 18 cases, dysferlin
      deficiency 8 cases and calpain-3 deficiency 5 cases. Only the sarcoglycans
      deficiency group showed calf hypertrophy. The dysferlin deficiency group was more
      frequent in females and the onset was later than sarcoglycan and calpain-3
      deficiency groups. The calpain-3 deficiency group occurred only in males and
      showed an earlier onset and weaker muscular strength.

PMID- 16100970
TI  - Experimental meningoencephalomyelitis by Encephalitozoon cuniculi in
      cyclophosphamide-immunosuppressed mice.
AB  - Encephalitozoonosis is an increasingly important opportunistic protozoan
      infection in immunocompromised individuals. This study aims to examine the
      development of an experimental Encephalitozoon cuniculi infection in the central
      nervous system of immunosuppressed mice. Adult Balb-C mice were inoculated
      intraperitoneally with E. cuniculi spores, treated with cyclophosphamide during
      the experimental period and killed from 15 to 75 days post-inoculation. Tissue
      samples were collected and processed for light and transmission electron
      microscopy investigation. Multifocal granulomas were seen in all organs. A
      lymphocytic, diffuse, non-suppurative menigoencephalomyelitis was observed, with
      neuronal degeneration and necrosis, macrophagic infiltration and reactive
      astrocytosis. E. cuniculi spores were seen in the microgranulomas or occurred
      unassociated with inflammatory reaction. The parasites were rarely seen in
      Hematoxylin-Eosin stained sections, but were Gram-Chromotrope positive.
      Proliferative forms and spores were found in parasitophorous vacuoles within
      neural cells and macrophages. Experimental encephalitozoonosis in
      immunosuppressed mice provides an useful model for the study of brain lesions
      associated with these protozoans in man.

PMID- 16100971
TI  - Internal structure of the cerebral hemispheres: an introduction of fiber
      dissection technique.
AB  - The aim of this study is to introduce the fiber dissection technique and its
      importance in the comprehension of the three-dimensional intrinsic anatomy of the
      brain. A total of twenty brain hemispheres were dissected. Using Kingler's
      technique we demonstrated the intrinsic structures of the brain. The supra
      lateral aspect of the brain as well as the medial aspect were presented. The most
      important fiber systems were demonstrated. The use and comprehension of new
      neuroimaging techniques demand a better understanding of this fascinating
      anatomy. The knowledge acquired with this technique will improve our
      understanding of critical pathways of the central nervous system.

PMID- 16100972
TI  - Microsurgical anatomy of the arterial compartment of the cavernous sinus:
      analysis of 24 cavernous sinus.
AB  - The cavernous sinus is a complex compartment situated in both sides of the sella
      turcica, being its microsurgical anatomy knowledge of fundamental importance when
      consider to approach surgically. We studied the arterial microanatomy of 24
      cavernous sinus at the microsurgical laboratory, considering that in all the
      internal carotid artery were filled with colored latex. The meningohypophyseal
      trunk was present in 18 cases (75%) with its origin in intracavernous portion of
      the internal carotid artery. In relation to the 18 presented cases with
      meningohypophyseal trunk, 14 (77.7%) had a trifurcate and 4 (23.3%) had a
      bifurcate pattern. The tentorial artery was present in all. Its origin was
      observed, arising from the meningohypophyseal trunk in 17 (70.8%) and as an
      isolated artery in some extension of the intracavernous portion in 7 (29.1%). An
      accessory tentorial artery was found in one specimen. The dorsal meningeal artery
      was present in 22 cases (91.6%). Its origin was in the meningohypophyseal trunk
      in 17 cases (77.2%), arising from internal carotid artery in 4 cases (18.1%) and
      from inferior hypophyseal artery in one case (4.1%).The inferior hypophyseal
      artery was present in all cases, having its origin at the meningohypophyseal
      trunk in 16 cases (66.6%). In the remaining 8 cases (33.3%) the artery was found
      arising alone from the intracavernous portion also. The artery of the inferior
      cavernous sinus or inferolateral trunk was present in all cases and had its
      origin from internal carotid artery in its intracavernous segment. The
      McConnell's artery was not found in any cavernous sinus.

PMID- 16100973
TI  - [Supratentorial-infraoccipital (or occipitopolar) approach: clinical and
      anatomical study].
AB  - Twenty-two patients harboring tumors or vascular lesions (AVMs and aneurysms)
      located at the posterior aspect of the parahipocampal gyrus and the pulvinar of
      thalamus operated by supratentorial-infraoccipital approach were analysed. Total
      resection was achieved in all five AVM patients as well as in six out of fifteen
      tumor patients. This approach was performed in five anatomical specimens (ten
      approaches); It results, along with the surgical results, allow this approach to
      be considered a good option for lesions of the pulvinar of thalamus and postero
      medial temporal lobe which are evident at the transverse fissure.

PMID- 16100974
TI  - [Interhemispheric supraorbital or frontopolar approach: anatomical study].
AB  - A modification of the supraorbital approach is proposed in order to improve the
      access to the medial portions of the anterior and middle fossas (supraselar
      region). It consists of a midline extension of the frontal craniotomy along with
      an interhemispheric approach: interhemispheric supraorbital or frontopolar
      approach. The anatomical basis of this approach were studied in eight cadaveric
      heads. Its results demonstratete that this approach adequaly access the medial
      structures of the anterior and medial fossas with minimal brain retraction and
      wide exposure.

PMID- 16100975
TI  - [Qualitative study of hippocampal formation in hypertensive rats with epilepsy].
AB  - The aim of our study was to investigate the hippocampus and dentate gyrus
      neuropathological features of spontaneous hypertensive rats (SHR) with epilepsy.
      METHODS: Animals were randomly divided into 4 groups: control Wistar, Wistar with
      epilepsy, control SHR and SHR with epilepsy. The pilocarpine model of epilepsy
      was used in this experiement. After spontaneous recurrent seizures, all animals
      were perfused and their brains processed for histological analysis through Nissl
      and neo-Timm methods. RESULTS: In the Wistar rats with epilepsy we observed cell
      loss in hippocampal subfields CA1, CA3 and hilus of the dentate gyrus when
      compared with control animals. In the SHR with epilepsy we observed hippocampal
      formation atrophy with ventricular dilatation. No morphological alterations were
      observed in SHR and Wistar control rats. The neo-Timm staining of hippocampal
      formation has shown supragranular sprouting in Wistar and SHR with epilepsy.
      CONCLUSION We found neuropathological alterations in hippocampal formation in
      Wistar with epilepsy and SHR with epilepsy, suggesting that epilepsy per se or
      associated to hypertention are able to cause neuronal damage.

PMID- 16100976
TI  - [Determination of electric current perception threshold in a sample of normal
      volunteers].
AB  - Reference values using the instrument Neurometer were determined and compared
      with those suggested by the manufacturer; the sensory thresholds for the
      different frequencies in different body segments were determined; the influence
      of age, level of education, gender and the reutilization of the electrodes in the
      different sites were also evaluated. Sensory threshold was determined in 101
      normal volunteers (68 women), ages ranged from 17 to 87 years old. The procedure
      was fully automated with the sensory threshold being determined by the method of
      limits followed by the forced choice method. Analysis of the results revealed
      that: there was a significant difference between the values obtained for the
      index fingers and the halux; no difference was detected between both index
      fingers; gender and level of instruction had no effect on the results, age had a
      small influence after stimulation with 2000Hz and 250Hz; three reutilizations of
      the electrodes did not affect the results on the index fingers, however at the
      halux, the third utilization deteriorated the results from the 2000Hz
      stimulation. Except for the 2000Hz stimulation, significant differences were
      suggested between the values reported here and those provided by the
      manufacturer.

PMID- 16100977
TI  - [Primitive reflex in premature healthy newborns during the first year].
AB  - A non-controlled, prognostic cohort study was performed with the aim of
      establishing markers of neurological development and defining a clinical and
      epidemiological profile of preterm newborns at 3, 6, 9, and 12 months of
      gestation-corrected age in terms of primitive reflexes evolution. RESULTS: At 3
      months old of corrected age, all primitive reflexes were present. At 6 months
      old, all children showed plantar grasp and 2.7% still showed Moro and palmar
      grasp. Plantar grasp was the unique primitive reflex found at 9 and 12 months of
      corrected age. CONCLUSION: It was possible to evaluate the occurence, as well as
      the disappearing of primitive reflexes in preterm newborns. The results show
      delay in the disappearing of primitive reflexes even with the use of corrected
      age.

PMID- 16100978
TI  - [Motor function evaluation in merosin-deficient congenital muscular dystrophy
      children].
AB  - Congenital muscular dystrophy (CMD) is a heterogeneous group of disorders
      characterized by early onset of hypotonia and weakness. Almost 50% of the cases
      are caused by primary deficiency of a protein named merosin (MD), and present a
      homogenous phenotype with a severe motor and respiratory involvement. Eleven
      children with clinical and histological diagnosis of CMD-MD, aged of 3 to 15
      years, were studied using the manual muscle testing (Medical Research Council),
      goniometric analysis, motor ability and day life activities (Barthel index)
      scales, with the objective to characterize the main motor function limitations.
      The muscular groups most affected were cervical flexors, paravertebral and
      proximal portions of limbs. The muscular groups of upper limbs were as affected
      as the lower limbs, and the extensors were more affected than the flexors groups.
      All children had severe muscular retractions on the hip, knee and elbow. Other
      frequent deformities were scoliosis and equinus-varum feet. No children presented
      the motor ability to walk, stand up and crawl; and all of them were classified as
      dependents or semi-dependents in the day life activities scale. Our findings
      confirm the severe and diffuse involvement of skeletal muscle in CMD-MD patients,
      producing serious motor limitations and deformities.

PMID- 16100979
TI  - [Interrater reliability for diagnosis in adults of attention deficit
      hyperactivity disorder and oppositional defiant disorder using K-SADS-E].
AB  - The diagnosis of attention deficit hyperactivity disorder (ADHD) and oppositional
      defiant disorder (ODD) in adults lacks adequate assessment instruments. The aim
      of this investigation is to evaluate the interrater reliability of the sections
      of K-SADS-E adapted for the diagnosis of these disorders among adults. The
      adaptations were limited to asking questions directly to the patient,
      investigation of a later onset of symptoms, and asking for adult specific
      symptoms. Six trained raters scored 16 recorded interviews. Kappa coefficients
      were 1.00 for ADHD diagnosis in the past, 0.91 for subtype in the past, 1.00 for
      ADHD diagnosis in the present, 0.95 for subtype in the present, 1.00 and 0.89 for
      ODD diagnosis in the past and present, respectively (all with p < 0.001). These
      results reveal excellent agreement for the ADHD and ODD diagnosis in adults using
      the adapted form of the Portuguese version of K-SADS-E.

PMID- 16100980
TI  - [Language impairment in the early stages of Alzheimer's disease].
AB  - Alzheimer disease (AD) is usually associated with cognitive, language and
      behavioral impairments, which can get more and more serious as the disease
      progresses. The aim of this study is to verify language disorders in the early
      stages of this disease. Twelve patients meeting criteria for problable AD were
      evaluated by the Boston test, and all of them scored more than 23 points on the
      Mini-Mental State Examination. Data acquired on this language evaluation were
      compared with the average of normal population data. All patients showed language
      disorders. Statistical differences were found in visual confrontating naming and
      auditory comphrension tasks. The patients performed well in writing and reading
      tasks. We believe that there might have had an interference in the patient's
      linguistic task performance due to their memory impairment. We could find
      language impairments in the early stages of AD.

PMID- 16100981
TI  - Isolated intracranial fibromuscular dysplasia presents as stroke in a 19-year-old
      female.
AB  - Isolated intracranial fibromuscular dysplasia is rare and may present with
      cerebrovascular events. It should be considered as etiology of stroke in
      otherwise healthy young patients. Though diagnosis is often challenging,
      characteristic morphologies may be revealed on magnetic resonance and catheter
      angiography. Cephalocervical fibromuscular dysplasia typically involves the
      extracranial portion of the internal carotid artery (nearly 95%). This rare case
      demonstrates isolated intracranial fibromuscular dysplasia in a 19-year-old
      female with left caudate and genu of internal capsule stroke.

PMID- 16100982
TI  - Bilateral olivary hypertrophy after unilateral cerebellar infarction.
AB  - We describe a case of bilateral olivary hypertrophy and palatal tremor after
      unilateral cerebellar infarction. Hypertrophic olivary degeneration (HOD) is
      associated with hypersignal in the inferior olivary nucleus (ION), on T2-weighted
      images. HOD has been more often observed ipsilaterally to a central tegmentum
      tract lesion or contralaterally to a dentate nucleus or a superior cerebellar
      peduncle lesion. Double innervation of each ION from either dentate nucleus may
      have underlied the imaging and clinical findings in this 63 year-old male
      patient.

PMID- 16100983
TI  - Factitious disorder mimicking addiction to levodopa in a patient with advanced
      Parkinson's disease.
AB  - We report a 43-year-old woman with early-onset Parkinson's disease in whom
      neurological control was impaired by psychiatric co-morbidity including major
      depression and panic disorder. The patient also met criteria for factitious
      disorder that mimicked dopamine dysregulation syndrome resulting in severe
      clinical and social disability.

PMID- 16100984
TI  - Acute myeloid leukaemia induced by mitoxantrone: case report.
AB  - Mitoxantrone (MX) is an immunosupressant drug used in secondarily progressive
      multiple sclerosis (SPMS) and in relapsing-remitting multiple sclerosis (RRMS).
      It has a leukemogenesis potential induced by cytogenetic abnormalities, though
      with a low incidence. Promyelocitic leukaemia (type M3) and other forms of acute
      myeloblastic leukaemias (M4 and M5) have been described in a few MS patients who
      received MX during their treatment. We describe a white female patient, 47 year
      old, with SPMS (EDSS = 4) with 14 years of disease. She received MX during her
      disease and developed acute promyelocytic leukaemia (M3), with severe
      thrombocytopenia 30 months later. She ultimately died due to intracerebral
      hemorrhage. Other cases of treatment related to AML are reviewed and discussed.

PMID- 16100985
TI  - Kennedy's disease phenotype with positive genetic study for Kugelberg-Welander's
      disease: case report.
AB  - We described a patient with clinical findings from Kennedy's disease and positive
      genetic study for Kugelberg-Welander's disease. A 24 years old man with negative
      family history presented with progressive spinal and bulbar muscular atrophy and
      gynecomastia at the age of 14. He was clinically diagnosed as having Kennedy's
      disease. However, a genetic study performed later was found to be negative for
      this disease and was positive for Kugelberg-Welander's disease, with deletion of
      the exons 7 and 8 in the "survival of motor neuron" gene.

PMID- 16100986
TI  - [Spheroid body myopathy: case report].
AB  - Spheroid body myopathy is a rare illness classified in the group of the
      congenital myopathies as a desmin-related neuromuscular disorder, presenting
      dominant autosomical origin with the beginning of the symptoms in the adult
      phase. We report on a seven years old girl with facial paresia, generalized
      muscular hypotrophy and hypotony, generalized deep areflexia, proximal upper and
      lower limbs muscular strengh and distal upper limbs grade 3 and distal lower
      limbs grade 1. Needle electromyography evidenced increased conscription and
      potentials of motor unit of short duration and low amplitude, characterizing a
      myopathic standard. The muscle biopsy disclosed mixed standard to myopathy,
      denervation and inclusion bodies that are consistent to spheroid body myopathy.
      In this case, the patient presented, in advance, early beginning of the symptoms
      and there are no similar cases in the family.

PMID- 16100987
TI  - Distal posterior inferior cerebellar artery aneurysm: case report.
AB  - The majority of posterior inferior cerebellar artery (PICA) aneurysms are usually
      found on the bifurcation of the vertebral artery (VA) - PICA junction. Aneurysms
      arising from more peripheral PICA segments named distal PICA aneurysm are
      uncommon. The major clinical manifestation is that of an intracranial bleeding
      and the site of hemorrhage is related to the PICA segment originating the
      aneurysm. Lesions originating from distal PICA segments, particularly those
      arising from the telovelotonsillar segment, are associated with hemorrhage
      extending into the ventricular system, mainly the i.v. ventricle. A case of a 50
      year-old woman with sudden headaches and vomiting, and intraventricular
      hemorrhage (four ventricles) caused by an aneurysm of the telovelotonsillar
      segment of the PICA, is presented. No signs of subarachnoidal hemorrhage were
      found in the computerized tomography. The aneurysm was clipped and the patient
      presented a favorable outcome. Anatomical aspects and clinical series are
      reviewed.

PMID- 16100988
TI  - Clip readjustment in aneurysm surgery after flow evaluation using the ultrasonic
      perivascular probe: case report.
AB  - Occlusion or stenosis of a parent vessel or its distal branches is a major cause
      of poor patient outcome after cerebral aneurysm surgery. Despite great attempts
      to preserve patency at the time of clip application, intraoperative visual
      observation may not reveal arterial compromise or occlusion. Quantitative
      measurement of blood flow in cerebral vessels during aneurysm surgery can help
      prevent ischaemia and improve patient outcome. We report a case of a large
      complex middle cerebral artery (MCA) aneurysm in which perivascular microflow
      probes were used to measure blood flow quantitatively in MCA and its branches
      before and after aneurysm clipping. Following aneurysm clipping, blood flow in
      the MCA branches were significantly reduced to less than its initial baseline
      value with occlusion of the inferior M2 segment. Prompt detection of compromised
      blood flow gave the surgeon the opportunity to adjust the clip. This adjustment
      was performed several times until restore MCA flow to its preclipping values.
      Intraoperative quantitative vessel-flow measurements were safe and may have
      prevented cerebral ischaemia and neurological deficit to this patient.

PMID- 16100989
TI  - [Congenital anomalies of the optic disc associated with moyamoya disease: case
      report].
AB  - Congenital anomalies of the optic disc can be associated with intracranial
      vascular abnormalities. We report a 9-year old boy with morning glory disc
      anomaly in one eye and optic disc and infrapapilar choroidal coloboma in the
      other. His past medical history was remarkable for a transient ischemic attack. A
      magnetic resonance angiogram of the brain was consistent with moyamoya disease.
      This case illustrates the important association between optic disc abnormalities
      and moyamoya disease. Funduscopic examination of suspicious cases can be helpful
      in establishing the clinical diagnosis. Early identification of the intracranial
      vascular anomalies may be of help in preventing severe neurological
      complications.

PMID- 16100990
TI  - [Semantic dementia: clinical and neuroimaging evaluation. Case report].
AB  - Semantic dementia is a clinical syndrome in the spectrum of frontotemporal lobar
      degeneration group. We report on a 63 years old man who presented with memory
      disorder of semantic nature for visual and mainly verbal material when he was 57
      years old. Mild behavior impairment was present and related to exaggerated
      responses to algic stimuli and repetitive behavior. Structural and functional
      neuroimaging methods disclosed asymmetric bitemporal damage, mainly on the left.
      Differential diagnosis should be considered with Alzheimer's disease, another
      subtypes of the frontotemporal lobar degeneration group and any other syndrome
      that presents with a fluent aphasic progressive disorder.

PMID- 16100991
TI  - [Dissecting aneurysm of the intracranial fenestrated vertebral artery submited to
      endovascular treatment: case report].
AB  - Dissecting aneurysms of the vertebral artery at its intracranial segment are
      uncommon lesions, mainly when associated to subarachnoid hemorrhage, being also
      rare fenestrations of the vertebral artery. They present high morbidity and
      mortality, with high rebleeding rate and difficulty of surgical approach. We
      present a 19 years old man who was victim of physical aggression in the occipto
      cervical region, presenting subarachnoid hemorrhage and a dissecting aneurysm of
      the right vertebral artery, which had a fenestration, being submitted to
      endovascular treatment. We accomplished a literature review about this subject,
      proposing endovascular treatment as a therapeutic option for these cases.

PMID- 16100992
TI  - [Epidural hematoma at the vertex: case report].
AB  - We report the unusual case of a 37 years old man with an epidural traumatic
      hematoma at the vertex with intracranial hypertension symptoms. The diagnostic
      was achieved with coronal cranial tomographic scans and a craniotomy was
      performed for hematoma removal.

PMID- 16100993
TI  - [Ictal electroencephalographic subclinical pattern in a case of benign partial
      epilepsy with centrotemporal spikes].
AB  - There are few reports of the ictal pattern of benign partial epilepsy with
      centrotemporal Spikes (BECTS) in the literature. This paper describes the case of
      a 7-year-old boy without significant perinatal history or psychomotor development
      delay. There was positive family history of seizures. Magnetic resonance imaging
      scans of the head was normal. The patient had a nocturnal isolated seizure,
      followed by a postictal motor deficit at the left arm. The EEG two days after the
      seizure showed a normal background activity with spikes in the centrotemporal
      bilateral area, and two subclinicals rhythmic discharges of spike and wave, with
      a duration of more than 50 seconds in the right centrotemporal area. This pattern
      of rhythmic discharge wasn not described in BECTS before.

PMID- 16100994
TI  - [Hyperammonemia secondary to the use of valproic acid: case report].
AB  - Valproic acid has been widely used for the treatment of epilepsy. Although it is
      usually well tolerated, it has been associated with some side effects. A poor
      studied side effect is the hyperammonemia, which independs from the drug
      hepatotoxic action. The hyperammonemia may occurs just after the beginning or
      during the treatment and is characterized by vomiting, progressive impairment of
      consciousness, focal neurologic signs and increased seizure frequency. We report
      boy a 6 year-old boy who presented with hyperammonemia during the use of valproic
      acid within the therapeutic range. Complementary investigation was negative for
      aminoacidopathy, organic acidemia and urea cycle disorders. The hypothesis of
      secondary effect to the valproic acid was reinforced by the normalization of
      ammonia levels after drug withdrawal. The pathogenesis of valproate-induced
      hyperammonemia have been discussed. We conclude that routine monitoring of
      ammonia blood concentration are strongly recommended in patients under valproic
      acid treatment.

PMID- 16100995
TI  - Neurological manifestations in celiacs and vitamin E status.

PMID- 16100996
TI  - Watching the pulse of the community.

PMID- 16100997
TI  - Are you ready for retirement?

PMID- 16100998
TI  - House to evaluate current state programs.

PMID- 16100999
TI  - What was said, what we heard.

PMID- 16101000
TI  - Changing the health of Michigan's communities through research.

PMID- 16101001
TI  - Workers' Compensation benefits: know and protect your rights.

PMID- 16101002
TI  - 101 ways to improve nursing culture: recognizing and managing conflict.

PMID- 16101003
TI  - Nursing and the Irish Traveller: toward a philosophy of cultural care.

PMID- 16101004
TI  - G-protein coupled receptor assays: to measure affinity or efficacy that is the
      question.
AB  - Cell-based assays have always played an important role in the pharmaceutical
      industry, providing information about the functional effects of compounds. These
      functional assays have traditionally accompanied facile biochemical high
      throughput screening programmes, being applied as secondary assays in the later
      stages of lead development. However, with the disappointing reality that there is
      not likely to be a plethora of novel, druggable targets in the post-genomic era,
      the role of cell-based assays in drug discovery is beginning to change.
      Competition to develop the "best" agents for well established targets and find
      more effective ways of identifying "novel" agents is driving the industry towards
      a "quality" versus "quantity" approach. Advances in genetic engineering,
      automation compatible functional assay technologies and the introduction of more
      sophisticated robotic systems, have facilitated the application of cell-based
      assays to primary screening. However, despite some apparent success to move these
      assays into the routine "toolbox" for high throughput screening, certain
      preconceptions and concerns about cell-based assays persist and the subject
      remains a topic of much debate. Here we use examples from the screening portfolio
      at Pfizer, Sandwich, to discuss the practical and theoretical considerations of
      employing cell-based assays in HTS with a focus on G-protein coupled receptors.

PMID- 16101005
TI  - The CellCard System: a novel approach to assessing compound selectivity for lead
      prioritization of G protein-coupled receptors.
AB  - Advances in high throughput screening technologies have led to the identification
      of many small molecules, "hits", with activities toward the target of interest.
      And, as the screening technologies become faster and more robust, the rate at
      which the molecules are identified continues to increase. This evolution of high
      throughput screening technologies has generated a significant strain on the
      laboratories involved with the downstream profiling of these hits using cell
      based assays. The CellCard System, by enabling multiple targets and/or cell lines
      to be assayed simultaneously within a single well, provides a platform on which
      selectivity screening can be quickly and robustly performed. Here we describe two
      case studies using the beta-lactamase and beta-galactosidase reporter gene
      systems to characterize G protein-coupled receptor agonist activity. Using these
      examples we demonstrate how the implementation of this technology enables assay
      miniaturization without micro-fluidic devices as well as how the inclusion of
      intra-well controls can provide a means of data quality assessment within each
      well.

PMID- 16101006
TI  - High content screening for G protein-coupled receptors using cell-based protein
      translocation assays.
AB  - G protein-coupled receptors (GPCRs) have been one of the most productive classes
      of drug targets for several decades, and new technologies for GPCR-based
      discovery promise to keep this field active for years to come. While molecular
      screens for GPCR receptor agonist- and antagonist-based drugs will continue to be
      valuable discovery tools, the most exciting developments in the field involve
      cell-based assays for GPCR function. Some cell-based discovery strategies, such
      as the use of beta-arrestin as a surrogate marker for GPCR function, have already
      been reduced to practice, and have been used as valuable discovery tools for
      several years. The application of high content cell-based screening to GPCR
      discovery has opened up additional possibilities, such as direct tracking of
      GPCRs, G proteins and other signaling pathway components using intracellular
      translocation assays. These assays provide the capability to probe GPCR function
      at the cellular level with better resolution than has previously been possible,
      and offer practical strategies for more definitive selectivity evaluation and
      counter-screening in the early stages of drug discovery. The potential of cell
      based translocation assays for GPCR discovery is described, and proof-of-concept
      data from a pilot screen with a CXCR4 assay are presented. This chemokine
      receptor is a highly relevant drug target which plays an important role in the
      pathogenesis of inflammatory disease and also has been shown to be a co-receptor
      for entry of HIV into cells as well as to play a role in metastasis of certain
      cancer cells.

PMID- 16101007
TI  - Functional G protein-coupled receptor assays for primary and secondary screening.
AB  - Screening technologies for G protein-coupled receptors comprise two major
      approaches; homogeneous assays, conducted in microtiter plate formats, and
      protein redistribution assays that require imaged-based analysis using automated
      confocal systems. Generally, the former are used in primary screening campaigns
      for lead identification, while the latter are used in secondary screens for lead
      optimization. Homogeneous assays measure changes in G protein-coupled receptor
      second messengers such as cAMP, Ins P3 or calcium. Protein redistribution assays
      assess internalization of the receptor ligand complex or translocation of G
      protein coupled receptor-associated proteins, such as beta-arrestin. In the
      present review functional cell based approaches are discussed, emphasizing the
      variety of non radiometric technologies now in use for HTS.

PMID- 16101008
TI  - Using IMAP technology to identify kinase inhibitors: comparison with a substrate
      depletion approach and analysis of the nature of false positives.
AB  - IMAP is a fluorescence polarisation-based assay method which can be applied to
      the measurement of protein kinase activity. Using a model serine/threonine kinase
      we found that IMAP generated a good assay window (Z' > 0.8), was very tolerant of
      DMSO, and was flexible with respect to sample processing (stopped reactions were
      stable over a period of several days). Using a set of six low molecular weight
      inhibitors of the kinase, we found a good correlation between IMAP and
      scintillation proximity assay (SPA) potency data. IMAP, which measures product
      accumulation, was compared in an HTS setting with a substrate depletion method
      (luminescence-based measurement of ATP concentration). There was a reasonable
      (approximately 50%) overlap in primary hits from a 17,000 compound set, but more
      apparent false positives were generated from the IMAP method. We followed up the
      compounds that showed activity in the IMAP method but not in the luminescence
      assay. Approximately 10% of these compounds displayed intrinsic fluorescence,
      suggesting that they were false actives by virtue of intrinsic spectroscopic
      properties. Compound activity by competition of phosphopeptide binding to IMAP
      beads can occur with high concentrations of chelating compounds, but did not
      occur with any of the false actives, suggesting that this form of interference is
      rare.

PMID- 16101009
TI  - Substrate specificity and novel selective inhibitors of TNF-alpha converting
      enzyme (TACE) from two-dimensional substrate mapping.
AB  - We report a systematic analysis of the P1' and P2' substrate specificity of TNF
      alpha converting enzyme (TACE) using a peptide library and a novel analytical
      method, and we use the substrate specificity information to design novel reverse
      hydroxamate inhibitors. Initial truncation studies, using the amino acid sequence
      around the cleavage site in precursor-TNF-alpha, showed that good turnover was
      obtained with the peptide DNP-LAQAVRSS-NH2. Based on this result, 1000 different
      peptide substrates of the form Biotin-LAQA-P1'-P2'-SSK(DNP)-NH2 were prepared,
      with 50 different natural and unnatural amino acids at P1' in combination with 20
      different amino acids at P2'. The peptides were pooled, treated with purified
      microsomal TACE, and the reaction mixtures were passed over a streptavidin
      affinity column to remove unreacted substrate and the N-terminal biotinylated
      product. C-terminal cleavage products not binding to streptavidin were subjected
      to liquid chromatography/mass spectrometry analysis where individual products
      were identified and semiquantitated. 25 of the substrates were resynthesized as
      discrete peptides and assayed with recombinant TACE. The experiments show that
      recombinant TACE prefers lipophilic amino acids at the P1' position, such as
      phenylglycine, homophenylalanine, leucine and valine. At the P2' position, TACE
      can accommodate basic amino acids, such as arginine and lysine, as well as
      certain non-basic amino acids such as citrulline, methionine sulfoxide and
      threonine. These substrate preferences were used in the design of novel reverse
      hydroxamate TACE inhibitors with phenethyl and 5-methyl-thiophene-methyl side
      chains at P1', and threonine and nitro-arginine at P2'.

PMID- 16101010
TI  - Rat PXR reporter-gene activity correlates with the induction of CYP3A in rat
      precision-cut liver slices.
AB  - Recent studies have suggested that both constitutive androstane receptor (CAR)
      and pregnane X-receptor (PXR) are involved in the induction of rat liver
      microsomal cytochrome P-450 (CYP) 2B and 3A through a mechanism called cross
      talk. In this study we intend to determine if a PXR-reporter gene assay could be
      used for the prediction of CYP3A and/or CYP2B induction in rats. The induction of
      rat CYP2B and CYP3A by nineteen structurally diverse compounds was evaluated by
      using rat precision-cut liver slices and a rat PXR reporter-gene system.
      Induction of CYP2B and CYP3A mRNAs in rat liver slices was quantified by real
      time polymerase chain reaction. Rat PXR activation was measured by induction of
      luciferase activity in rat PXR reporter-gene system. Linear regression analysis
      of the fold of induction of mRNA in liver slices and the fold of luciferase
      activity in rat PXR reporter-gene system shows that a reasonable correlation (r2
      = 0.6) exists between the CYP3A induction and the rat PXR activation. A much
      lower correlation was observed between CYP2B induction and the rat PXR activation
      (r2 = 0.1). The results from this study suggest that the PXR may play a major
      role in the induction of rat CYP3A, but not CYP2B. Therefore, the PXR-reporter
      gene assay may be useful in a high-throughput screening to predict CYP3A
      induction in rats.

PMID- 16101011
TI  - Identification of nitric oxide donors by biomimetic HTS application.
AB  - Metalloporphyrin catalyzed biomimetic oxidation was used for the identification
      of nitric oxide (NO) donors with diverse chemical structure. Methodology was
      validated by testing known NO donors. Efficient automation of the test allowed us
      to investigate a subset of our corporate library. Several hits identified in this
      campaign were validated in both the chemical and also microsomal model that
      revealed all hits to be active in the biological system, as well. One of the hits
      showed comparable activity to V-PYRRO/NO, the prototypic liver selective NO
      donor.

PMID- 16101012
TI  - High throughput coagulation analyzers review.
AB  - The increasing no. of ordered coagulation screening tests has led to a remarkable
      improvement in the efficiency of automated coagulation testing, and appearance of
      a new generation of high throughput analyzers ensuring accuracy and precision,
      and reducing the strain and human error. The earliest analyzers operated
      mechanically, using the hook to detect the clot in the cuvette are now replaced
      with more sophisticated analyzer that simultaneously uses the clotting,
      chromogenic, and immunological principles, to provide a versatile test menu
      covering antigenic and functional aspects of coagulation. The armamentarium of
      coagulation testing is complimented with tools like; automated platelet function
      analyzer, flowcytometer, and molecular techniques including the polymerase chain
      reaction, and lately the microarrary (biochip) technology. This review addresses
      the principle of operation and distinctive features of various automated high
      throughput coagulation analyzers, their impact on improving efficiency,
      eliminating preanalytical and postanalytical handling thus maximizing
      productivity and return on investment.

PMID- 16101013
TI  - Recent advances in analytical construct resins.
AB  - The area of solid-phase synthesis has witnessed exponential growth in the last
      fifteen years, but difficulties associated with the monitoring and analysis of
      resin-bound reactions and products have been apparent due to a limited number of
      analytical methods available. With the substrate tethered to an insoluble support
      traditional chromatographic monitoring is only possible after cleavage. In order
      to address this 'analytical bottleneck' Geysen, in 1996 elaborated Merrifield's
      initial dual linker strategy by incorporating an encoding system between two in
      line linkers. These analytical construct resins represented a new approach for
      both the quality control of solid-phase combinatorial libraries and for the
      development of new synthetic sequences on solid-support. This review will
      summarize the development and application of analytical construct resins focusing
      on recent applications of the technology.

PMID- 16101014
TI  - 1303-2003: 700 years of history in the University "La Sapienza", Rome. The
      Medical Faculty in Rome in the early modern age.

PMID- 16101015
TI  - Malpighi's anatomo-physiology as a synthesis of mechanism and corpuscolarism.
      Kidneys and lungs: an epistemological model.

PMID- 16101016
TI  - Calcium signaling in terminal Schwann cells associated with lanceolate sensory
      endings in rat vibrissae.
AB  - Transient elevations of the intracellular Ca2+ concentration ([Ca2+]i) in glia
      mediate various cell activities to regulate neuronal functions. The present study
      focuses on spatiotemporal dynamics of Ca2+ signaling in terminal Schwann cells,
      glial elements of the lanceolate sensory endings innervating the rat vibrissa.
      Arrays of lanceolate endings were enzymatically isolated from the vibrissal
      follicle, and subjected to [Ca2+]i image recording by time-lapse confocal
      microscopy. Each terminal Schwann cell displayed a round cell body, and extended
      long cytoplasmic stalks, which branched into two to five lamellae resting on
      different axon endings. Each axon ending, on the other hand, was covered on both
      flattened sides of the lancet by two Schwann lamellae of different cell origin.
      Thus the peripheral glia constituted an extensive network connecting the sensory
      endings. Image analyses of [Ca2+]i characterized the Schwann lamellae as
      functional compartments that can independently generate Ca2+ signals: these cell
      portions primarily responded to local mechanical stimuli with a [Ca2+]i spike,
      and individually initiated [Ca2+]i oscillations during bath application of the
      sensory modulator adenosine 5'-triphosphate (ATP). The stimulus-induced signals
      sometimes propagated along the glial network to activate neighboring lamellae
      after a delay of 2-4 sec. These findings suggest that the terminal Schwann cells
      contribute both to individual regulation and total coordination of the arrayed
      sensory endings.

PMID- 16101017
TI  - Dopamine nerve fibres and related receptors in bronchus-associated lymphoid
      tissue (BALT).
AB  - Age-related changes of the dopamine nerve fibres of bronchus associated lymphoid
      tissue (BALT) were investigated in male Wistar rats of 3 months (young), and 24
      months (old/aged). Dopamine histofluorescence techniques have been used,
      associated with image analysis for the detection of dopamine nerve fibres. In
      young rats, white, fluorescent nerve fibres supply BALT. This tissue is
      innervated by a delicate network of nerve fibres rich in varicosities. In old
      rats these fluorescent nerve fibres are strongly reduced. Moreover, dopamine D1a
      and D1b receptors were stained using fluorescent monoclonal antibodies. The BALT
      of young rats possesses a higher number of D1a and D1b receptors, while, in the
      old rats, these receptors are strongly reduced. The possible significance of
      reduced dopamine neurotransmission in BALT of aged rats is discussed.

PMID- 16101018
TI  - Heroin sensitization induces circumventricular organ activation in the rat brain.
AB  - Using c-Fos protein immunohistochemistry we previously demonstrated various sites
      of activation in the rat forebrain according to the animal's drug history. This
      study originates from a more detailed evaluation ex-post of the same specimens. A
      discrete number of c-Fos protein immunoreactive nuclei could be observed in some
      circumventricular organs, including the vascular organ of terminal lamina (OVLT)
      and subfornical organ (SFO) and in the nucleus of solitary tract near the area
      postrema, but only in specimens from sensitized rats. We therefore suggest that
      repeated drug injections activate the normally low drug metabolizing enzyme
      activity in the circumventricular organs thus implicating these organs in the
      complex mechanisms underlying behavioral sensitization.

PMID- 16101019
TI  - Effects of neurotrophin-3 gene mutation in the expression of neurocalcin.
AB  - Neurocalcin (NC) is a neuron-specific "EF-hand" calcium-binding protein present
      in a non-fully characterized subpopulation of dorsal root ganglion (DRG) neurons,
      some kinds of mechanoreceptors and proprioceptors, and in motor end-plates. In
      the present study we have characterized NC expression in spinal sensory and motor
      neurons, and their endings in newborn mouse. Because the neurotrophic factor
      neurotrophin-3 (NT-3) appears to plays a major role in the development and
      maturation of sensory and motor neuronal populations, we have studied NC
      immunoreactivity in newborn NT-3 null mutant. In NT-3 deficient animals the
      overall number of NC-immunoreactive DRG neurons was reduced by as much as 70%
      including all large neurons, but subpopulations of NC expressing small and
      intermediate-sized neurons survived. As expected no muscle spindles were found in
      NT-3 mutant mice while they were present and normally innervated by NC-positive
      nerve fibers in wild-type animals. On the other hand, NC immunoreactivity was
      dramatically decreased in motoneurons of the spinal cord, ventral root nerves and
      motor end-plates in the absence of NT-3. The present results demonstrate that NC
      containing DRG neurons include all proprioceptive, and a subset of
      mechanoreceptive and proprioceptive. Furthermore, they strongly suggest that NT-3
      is involved in the maturation of motor end-plates.

PMID- 16101020
TI  - Effects of hyperthermia in human neuroblastoma cells.
AB  - Neuroblastoma is a childhood malignancy derived from the developing sympathetic
      nervous system (SNS) and often diagnosed during early infancy. To investigate its
      metastatic properties, also in response to anti-cancer treatment, we have studied
      hyperthermia (HT) effects on the ultrastructure of SK-N-MC human neuroblastoma
      tumor cells. Cells undergoing HT showed a significant increase in apoptotic and
      necrotic events, but also a rearrangement of the cellular shape, appearing as
      cell detachment and rounding. The most striking effects of HT can be so
      correlated to primary tumor mass decrease and to a certain impairment of cell
      adhesion properties and consequently metastatic diffusion potential.

PMID- 16101021
TI  - Comparative morphological study on the tongue and lingual papillae of horses
      (Perissodactyla) and selected ruminantia (Artiodactyla).
AB  - A common characteristic of horses, Rocky Mountain goats, and cattle is that they
      all have a well developed lingual prominence on the dorsal surface of the
      posterior area of the tongue. Foliate papillae were found in the horse studied
      but not in the goat or in cattle. The horse filiform papillae had a long and
      slender external form with a thin and slender CTC, while in the goat and cattle
      the external form consisted of a large thick main process and the CTC consisted
      of a bundle of numerous rod-shaped protrusions. The special papilla found on the
      lingual prominence resembled larger filiform-like papillae in the horses;
      however, in the goat and cattle it was a very thick and large tongue like
      papillae. The horses had two large vallate papillae, while the goat and cattle
      had 15 or more vallate papillae at the posterior area of the lingual prominence.
      This suggests that the fine structure of horse tongues may display a more
      primitive pattern than that present in goats and cattle.

PMID- 16101022
TI  - Morphological alterations induced by cytochalasin D on serous cells of human
      submandibular gland in basal and stimulated conditions.
AB  - Cytochalasin D (CD) is a fungal toxin which binds to the faster growing end of
      actin microfilament and inhibits actin polymerization. By an in vitro incubation
      system of slices of human submandibular glands obtained at surgery, we
      investigated by light microscope (LM), transmission electron microscope (TEM),
      and high resolution scanning electron microscope (HRSEM) the morphological
      changes caused by CD on serous cells. We studied the effects of the drug on
      secretory events induced by isoproterenol (I) and carbachol (C). With LM,
      following CD incubation, canaliculi were enlarged and prominent vacuoles were
      seen throughout the cytoplasm. By TEM, the vacuoles, which in many cases were in
      continuity with the lumen, represented the distinctive feature of secretory
      cells. With HRSEM, intercellular canaliculi, seen from their cytoplasmic side,
      exhibited many small spherical bulges, corresponding to the coated pits seen with
      TEM and indicating that the retrieval of plasma membrane was arrested at an early
      phase by the disruption of the actin cytoskeleton. In specimens treated with
      secretagogues and CD, a consequence reported here for the first time was the
      presence of dense granules within the vacuoles. The protrusions seen by HRSEM on
      the cytoplasmic side of intercellular canaliculi, following secretagogues
      stimulations, appeared peculiar to each stimulants, even if combined with CD,
      suggesting that besides actin filaments, other components, unaffected by CD, also
      are involved in the process of exocytosis and related phenomena.

PMID- 16101023
TI  - Hepatic microcirculation and cholangiocyte physiopathology.
AB  - BACKGROUND: The peribiliary plexus (PBP) plays a fundamental role in supporting
      the functions of the biliary epithelium. After common bile duct ligation (BDL)
      progressive PBP proliferation is demonstrated. We have, recently, demonstrated
      that the biliary epithelium express Vascular Endothelial Growth Factor (VEGF),
      both subtype -A and -B and VEGF receptors. Taking in consideration the wide
      extension of PBP during BDL, aim of our study is to investigate the role of VEGF
      in stimulating angiogenesis and also in the modulation of epithelial cells
      proliferation. MATERIAL AND METHODS: Experimental studies were performed by
      evaluating the effects of: a) endogenous VEGF neutralization by chronic
      administration of anti VEGF-C antibody on cholangiocyte proliferation in BDL rats
      and; b) the hepatic artery ligation (HAL) immediately after BDL followed by
      treatment (7 days) with a recombinant of VEGF-A (administered through IP
      implanted minipumps) on cholangiocyte proliferative activities. RESULTS: Both
      administration of antiVEGF-C antibody and HAL decreases cholangiocyte
      proliferation. The decrease of cholangiocyte proliferation was associated with
      depressed VEGF-A protein expression. The administration of rVEGF-A to BDL,
      hepatic artery ligated rats prevented the decrease of cholangiocyte proliferation
      and VEGF-A expression as compared to BDL control rats. CONCLUSION: These data
      suggest that VEGF-C modulates the proliferative activities of cholangiocytes in
      experimental cholestasis and that circulating factors (i.e., VEGF) in the blood
      supply of the intra-hepatic biliary epithelium, play an important role in the
      balance between cholangiocyte proliferation/loss.

PMID- 16101024
TI  - Three-dimensional distribution of the collagen fibers in the submucosa of the
      swine terminal ileum.
AB  - Collagen has an important role in controlling mechanical function and
      physiopathology of intestinal wall. Swine small intestine may be used as
      biomaterial source for tissue repairing. Changes of collagen arrangement and
      three-dimensional (3D) distribution may be related to the dissimilar
      biomechanical proprieties showed by different intestine tracts. 3D spatial
      distribution of collagen bundles of swine submucosal terminal ileum (SSTI) was
      studied by a correlated analysis of light (LM) and scanning electron microscopy
      (SEM) of NaOH macerated samples. Bundles of collagen fibers were greatly
      represented in the submucosa at the mesenteric border and also extended along the
      longitudinal folds beneath mucosa layer. Polarized LM of picrosirius stained
      samples evidenced yellow and red fibers (type I collagen), and green fibers (type
      III collagen). Silver-impregnated sections showed predominant brown-stained
      fibers and, in a smaller amount, black-stained ones. By SEM submucosal collagen,
      isolated by NaOH maceration, appeared arranged in wide bundles forming a
      complicated 3-D network. The bundles presented a sinuous course, opened and
      closed repeatedly forming meshes fashioned in a regular net. These observations
      originally demonstrated that 3-D distribution of SSTI collagen is different from
      that observed in other gut segments and species. The arrangement of SSTI collagen
      fibers that we observed seems to be morphofunctionally adjusted to provide
      appropriate resistance to mechanical forces and to assure compliance to
      deformations induced by intestinal wall motion. The studies for selection of
      optimal intestinal patches for surgical replacement should take into
      consideration the basic morphological evaluation of parietal collagen 3D
      distribution.

PMID- 16101025
TI  - Analysis of microvascular trees by means of scanning electron microscopy of
      vascular casts and 3D-morphometry.
AB  - Arterial and capillary trees form by consecutive branching (mostly bifurcations)
      from a stem vessel, venous trees form by repeated merging of blood vessels.
      Diameters of stem (parent, mother) vessels and daughter vessels (branches),
      interbranching distances and branching angles between stem and daughter vessels
      lastly define the overall three-dimensional structure of the vascular network as
      well as the basic transport capacity of the system. Here we use scanning electron
      microscopy and 3D-morphometry to measure these variables from stereo paired
      images of vascular corrosion casts of the anterior cerebral artery and its main
      branches and from arteriolar bifurcations of the mesencephalic optic tectum in
      the actinopterygian fish, Acipenser ruthenus. We then calculate bifurcation
      indices, area ratios, asymmetry ratios and test for the optimality principles
      underlying the bifurcations studied. Our results show that arteriolar
      bifurcations in the optic tectum are in favor of the principles of minimum
      pumping power and minimum volume rather than the principles of minimum surface
      and minimum drag. We conclude that scanning electron microscopy of vascular
      corrosion casts in conjunction with 3D-morphometry is an excellent tool to
      thoroughly analyze vascular trees in healthy and diseased tissues and organs, as
      well as on an ontogenetic and phylogenetic scale.

PMID- 16101026
TI  - The "interfascial" veins of the lower limbs.
AB  - The veins of the lower limb are commonly divided in deep and superficial ones
      according to their position with respect to the Muscular Fascia (MF). Anatomical
      textbooks affirm that all superficial veins are thin walled vessels that run in a
      yielding layer of fat. Accordingly, no differences between saphenous Veins (SVs)
      and their tributaries (TVs) are reported by physiologists and pathophysiologists.
      On the contrary, the SVs do not correspond to the classic anatomic, physiologic
      and clinical descriptions of the "superficial" veins. In fact, the SVs: 1) are
      not superficial because they course between the SF and the MF; 2) they are not
      thin vessels, being their wall thick and rich in muscular cells; 3) they actively
      contribute to the complex mechanisms of venous return from the lower limbs; and
      finally, 4) they are quite resistant to hypertension and usually afflicted with
      limited varicose changes. As a consequence, the SVs should not be longer
      considered "real" superficial veins and the venous bed of the lower limb would be
      better represented by a three-layered model.

PMID- 16101027
TI  - Pored domes in adrenocortical capillaries. An ultrastructural study in mammals.
AB  - The adrenocortical gland is one of the most vascularized organs of the mammalian
      body. It undergoes continuous morphological changes dynamically dependent upon
      special permeability conditions related to various physiological and
      physiopathological events. The adrenal cortex of different adult mammals (3 pigs,
      2 mice, 3 sheep) was studied by means of scanning (SEM) and transmission (TEM)
      electron microscopy. As seen by SEM it is formed of polyhedral cells which
      delimit a characteristic continuous labyrinth system of intercellular lacunae
      occupied by sinusoid-like capillaries. The capillary wall is fenestrated and is
      lined by flattened endothelial cells with their nuclear part bulging into the
      capillary lumen. The fenestrae are round or oval pores measuring 50-100 nm in
      diameter. They are usually clustered to form sieve plates and characteristically
      present a thin membranous diaphragm. Irregular microelevations and dome-like
      projections are often seen. These structures are made of thin cytoplasmic plates
      interrupted by numerous small pores which show a sieve plate profile. The pored
      domes on the nuclear portion seem to be identical in structure to those found in
      the thinner endothelial part; some of them appear to detach from the endothelial
      cell. The pored-domes are structurally comparable to those reported both in the
      renal glomerular endothelium and in liver sinusoids. These endothelial structures
      may be an expression of the high rate of filtration of these tissues and may be
      also related to the final step of the replacement of the sieve plates during
      endothelial regeneration.

PMID- 16101028
TI  - Morphological analysis of cell subpopulations within carotid atherosclerotic
      plaques.
AB  - Atherosclerosis is considered a chronic inflammatory process, prompted by lipid
      accumulation and propagated by cell-mediated mechanisms. The present work was
      undertaken to clarify this process by characterizing cellular components of
      inflammatory infiltrate localized within atheroma. Cryostat sections of
      atherosclerotic lesions obtained from human carotid endarterectomy were analysed
      immunohistochemically by using monoclonal and polyclonal antibody directed
      against T cell subpopulations (CD3, CD4, CD8), B cells (CD20), plasma cells
      (CD138), macrophages (CD14), mast cells (anti-tryptase). Our results assess that
      T cells are the predominant cell type among plaque infiltrating inflammatory
      cells. B cells were detected near the lipid core of atheroma and clusters of
      plasma cells were observed within cellular infiltrates in most plaques. Numerous
      tryptase positive mast cells were noticed in many areas of complicated lesions.
      Our results indicate the presence of many inflammatory cells within type V and VI
      atherosclerotic plaques, suggesting the involvement of those cells in plaque
      progression. In fact it was previously shown that stability of atherosclerotic
      lesions is influenced by mast cell-released matrix metalloproteinases which
      induce plaque rupture and by cytokines and chemokines which increase local
      inflammatory response and are produced by lymphocytes and macrophages.

PMID- 16101029
TI  - Short-term patency of 1 mm diameter PTFE prosthesis: an angiographic, Doppler
      flowmetric and morphological experimental study.
AB  - Expanded polytetrafluoroethylene (PTFE) prostheses may be used in peripheral
      vascular surgery. Due to contradictory results on patency rate and neointimal
      formation, the effectiveness of this kind of prosthesis in small caliber artery
      reconstruction is still under discussion. In order to evaluate the effectiveness
      of this technique 1 mm internal diameter PTFE prosthesis (fibril length 35
      microm) interposed in rabbit femoral artery, for 15 and 30 days, were studied
      functionally and morphologically. Doppler was performed during surgery, at day 2,
      15 and 30. Arteriography was carried out at day 1. Light microscopy and scanning
      electron microscopy were performed on prosthesis sampled at day 15 and 30.
      Doppler flowmetry showed the full patency in all PTFE prosthesis. Angiography
      confirmed that all PTFE grafts were patent after 24 h. Doppler flowmetry,
      performed after 15 and 30 days, showed a reducing patency rate respectively at
      70% (21 grafts) and 60% (18 grafts). Morphological studies showed that
      endothelial lining was not present at 15 day. After 30 days proliferation of
      blood cells occurred in the graft wall. Lumina presented a fibrous lining and did
      not show significant endothelial cell growths. These results confirm that PTFE
      prosthesis represents a suitable alternative to biological graft for the repair
      of small caliber artery when the latter are not available. Autologous vein is the
      vascular substitute of choice for peripheral vascular reconstruction, and PTFE
      prosthesis may be quite successfully used as a secondary choice, when multiple
      reconstruction are needed and biological grafts are not sufficient.

PMID- 16101030
TI  - Shedding of membrane vesicles by tumor and endothelial cells.
AB  - Shedding of membrane vesicles is a vital phenomenon frequently observed in tumor
      cells and suggested to be involved in several aspects of tumor progression. Our
      previous studies have shown that human breast tumor cells rapidly shed membrane
      vesicles containing matrix metalloproteinases (MMPs). In this study we present
      that human umbilical vein endothelial cells (HUVEC) as well as different tumor
      cell lines (human ovarian cancer, CABA I and A2780, and hepatocarcinoma cell
      line, SK-Hep 1) shed vesicles in the extracellular medium. These vesicles carry
      MMPs and their inhibitors TIMPs. We conclude that tumor and endothelial cells
      shed MMP-containing vesicles and this may represent a mechanism for regulating
      focalized proteolytic activity and a way to interact with microenvironment during
      tumor angiogenesis.

PMID- 16101031
TI  - Invasive properties of multidrug resistant human melanoma cells.
AB  - Melanoma cells exhibit a high level of intrinsic or acquired resistance to the
      cytotoxic agents often associated with the over-expression of drug transporters
      such as P-glycoprotein (P-gp). In this in vitro study, we investigated the
      possible relationship between P-gp and CD44, the cell adhesion molecule involved
      in metastasis and tumor progression of melanoma cells. CD44 expression appeared
      to be similar in the parental sensitive M14 WT cells and in their resistant
      counterparts M14 ADR cells. Double-labeling of cryosectioned cells showed that P
      gp and CD44 were transported from the synthesis loci to the cell periphery by
      different vesicles and began to coalesce in proximity of the plasma membrane;
      thus, P-gp and CD44 seemed to reach together the cell surface. Moreover, P-gp and
      CD44 appeared to be associated with ERM proteins. The invasive activities of both
      M14 WT and M14 ADR cells were analyzed by the "transwell chamber invasion" assay.
      M14 WT cells revealed low capacity to traverse the filters, both in the absence
      (motility) and in the presence (invasion) of a Matrigel coating. In comparison,
      M14 ADR cells displayed significantly higher motility and invasion. SEM
      observations showed that sensitive cells employed lamellar cytoplasmic extrusions
      to pass through the filter pores whereas resistant cells elongated along the hole
      through globular processes. In conclusion, the results herein reported suggest
      that drug resistance in melanoma cells appears associated with a more aggressive
      behaviour. P-gp and CD44 might cooperate to confer this more invasive phenotype.

PMID- 16101032
TI  - Fertilization and developmental initiation of oocytes by injection of spermatozoa
      and pre-spermatozoal cells.
AB  - The essence of fertilization is the union and mingling of male and female
      genomes. Therefore it is not surprising that microsurgical deposition of a single
      spermatozoon in an oocyte (ICSI) results in the development of normal offspring.
      Poorly motile or structurally aberrant spermatozoa, which are unable to fertilize
      under ordinary conditions, are not necessarily genomically abnormal. This is the
      reason why normal offspring are obtained after ICSI using such spermatozoa. At
      present, ICSI is most successful in humans and mice, but there is no reason to
      believe that ICSI does not work in other animal species as well. Injection of
      round spermatids into oocytes (ROSI) works routinely in the mouse, but it is
      controversial in humans. While some investigators have claimed successes, many
      others have reported complete failure. There must be several reasons for this,
      including the difficulty of distinguishing true spermatids from other small
      cells. Insufficient oocyte activation following ROSI and the functional
      immaturity of the centrosome could also be responsible for this. In mice, it is
      possible to obtain normal offspring by injection of primary or secondary
      spermatocytes into oocytes. The nucleus of a spermatocyte undergoes meiotic
      division(s) within the oocyte's cytoplasm before a haploid sperm pronucleus
      unites with an oocyte's haploid pronucleus. However, only a few of the produced
      zygotes have developed into fertile offspring. There are many hurdles to clear
      before ROSI and spermatocyte injection becomes efficient and medically safe
      methods for assisted fertilization.

PMID- 16101033
TI  - Human embryonic stem cells and their spontaneous differentiation.
AB  - Human embryonic stem cells (hESCs) usually grow in saucer-shaped colonies with
      thickened rims and can form spherical human embryoid bodies (hEBs) under non
      adherent conditions. A problem associated with ES cell culture is the spontaneous
      differentiation of cells into a variety of cell types representing all three germ
      layers, which is evident in both hESC colonies and hEBs. This presentation deals
      with the precise origins of hESCs and their spontaneous differentiation in vitro.
      We have used advanced digital microscopy, including transmission electron
      microscopy (TEM) to define the fine structure of these cells. We present images
      of undifferentiated hESCs and their spontaneous differentiation into basic
      embryonic cell types such as nerve, muscle, connective tissue, epithelium, and
      digestive tract progenitors, representing all three primary germ layers:
      embryonic ectoderm, mesoderm and endoderm. It appears that hESCs work in concert
      and interact with one another, as in tissue formation of the embryo. Our fine
      structural observations agree mostly with those of the Thomson group. Digital
      microscopy of plastic sections and TEM are invaluable tools in the precise
      characterization of cells forming these tissues and a combined study with
      immunofluorescent markers is most desirable.

PMID- 16101034
TI  - Melatonin as protective agent for the cytotoxic effects of diazinon in the
      spermatogenesis in the earthworm Eisenia foetida.
AB  - Diazinon (D) is an organophosphorate synthetic insecticide widely used in the
      world. It inhibits acetylcholinesterase activity and damages reproduction as well
      as other organic functions mostly by increasing lipid peroxidation. Melatonin (M)
      is an indolamine secreted by the pineal gland. It performs numerous functions but
      recently it has been proposed as a good scavenger of oxygen radicals. The
      earthworm E. foetida is reputed as an excellent bioindicator of environmental
      chemical pollution. The testicular toxic effect of D and the protective role of M
      was analyzed in adult E. foetida, at 1, 7, 10, 15 and 30 days after exposure to
      1/4, 1/2 and 3/4 of LD50. Sperm counts and the diameter of the seminal
      receptacles and of their lumina were altered in D exposed worms, which in
      addition have a lower percentage of survival, decreased weight and show
      cholinergic effect (coiling of the tail). All these changes were prevented fully
      or in part by simultaneous exposure to M. The observations confirm that D is a
      general and testicular toxicant for E. foetida, a good sentinel indicator and
      stresses the role of M as a protective agent.

PMID- 16101035
TI  - Emergence of a glomus-like body in the human yolk sac: a microanatomical analysis
      of its structure.
AB  - Since the last decade the Yolk sac (YS) has been a topic of increasing interest
      due to the growing use of high-resolution sonography in early determination of
      pregnancy. Human YS shape and diameter are indicators of viability of pregnancy
      during the early embryonic period. Nevertheless, the major interest concerns the
      vital function it plays in early embryo growth and development. Two compartments
      are recognized in this organ: the yolk sac proper and the vitelline stalk. In
      this study we report the identification and partial characterization of a glomus
      like body in the wall of the secondary YS in humans. A detailed structural
      description is also presented on the time course of formation of this new
      structure, at precisely sequential stages between 4-8 wk post-conception. The
      significance of this new compartment on the YS function is analyzed. Light and
      scanning electron microscopy were used to investigate the microstructure of the
      YS and the vitelline stalk during the first 8 wk of development. Ten YSs were
      collected from embryos (aged between 24-50 days) obtained from emergency
      salpingectomies due to tubal ectopic pregnancy. From 5 wk onward a new structure
      was observed in the YS located near the apex of the pear-shaped yolk vesicle and
      closed to the connecting stalk. We designate this differentiation as glomus-like
      body. This structure is 1-1.5 mm long and merged from a pocket-like structure of
      the extraembryonic splanchnic mesoderm of the YS wall. It likely represents an
      area of convergence of the vascular network of the YS wall. Our findings
      underline the remarkable complexity of the human secondary yolk sac during early
      development. The detailed description of the microanatomy of this vital organ is
      of theoretical and practical interest in order to unravel the mechanisms used by
      the yolk sac to transport nutrients to the embryo.

PMID- 16101036
TI  - Ultrastructure of the maternal-fetal interface of the yolk sac placenta in
      sharks.
AB  - The blacknose shark, Carcharhinus acronotus, is a viviparous anamniote that
      develops an epitheliochorial yolk sac placenta. The fetal portion of the
      uteroplacental complex consists of a proximal portion that forms saccular
      evaginations. The cells are bilayered stratified squamous with surface microvilli
      and a high concentration of cytoplasmic filaments. The tertiary egg envelope
      intervenes between the distal portion of the placenta and uterus. It has
      delaminations on the uterine surface and is compacted on the placental surface.
      The uterine epithelium is cuboidal to columnar and is characterized by prominent
      RER, Golgi, and secretion vesicles. The capillary endothelium is continuous.
      Nutrient and respiratory exchange is effected between the uterus and distal
      portion of the yolk sac. The distal portion of the placenta is a bilayer. An
      elaborate array, of microvilli forms an interface with the egg envelope. Dense
      non-membrane bound granules occur in the interspace between the egg envelope and
      the distal placenta. This material, presumably of uterine origin, is endocytosed
      in smooth-walled vesicles of the placental cells. The endothelium of the
      capillaries is fenestrated.

PMID- 16101037
TI  - Growth factors and their receptors: fundamental molecules for human placental
      development.
AB  - In this review we present data concerning the localization of some important
      growth factors and their receptors in the human placenta. We focus our attention
      on molecules playing a fundamental role in angiogenesis and morphologic processes
      as beta-FGF, EGF and TGF-beta. The distribution of these growth factors and their
      receptors in the placental villi during gestation suggests that these molecules
      play a pivotal role in growth and differentiation of the villous tree.

PMID- 16101038
TI  - In vitro culture of mammalian early ovarian follicles. Morphofunctional
      correlates and future perspectives.
AB  - In vitro growth culture systems of mammalian oocytes have been developed with the
      aims of studying regulative processes occurring during oogenesis and
      folliculogenesis, and of preserving fertility. Although in large mammals IVG
      technology does not still assure the co-ordinate development of both somatic and
      germinal cells and the production of high number of viable offspring, their
      improvement may represent an important therapeutic tool for restoring fertility
      in women undergoing premature menopause or cancer treatments. Morphological
      studies of in vitro grown follicles were not performed extensively, especially by
      means of scanning electron microscopy. In the present paper preliminary
      ultrastructural observations of in vitro cultured follicles are presented.

PMID- 16101039
TI  - Somatic cell amplification of early pregnancy factors in the fallopian tube.
AB  - This essay is concerned with the function of ovarian somatic cells, especially
      those of the cumulus oophorus, that are shed with the oocyte at the time of
      ovulation. Once dissociated from the surface of the oocyte(s), they remain in its
      close vicinity or that of the zygote(s) throughout the tubal sojourn. Most such
      follicular cells are not moribund or dead but continue to be synthetically
      active, although showing ultrastructural modification. Their secretions may
      include steroid hormones, prostaglandins and diverse peptides, molecules that
      would be presented locally to the endosalpinx. The cell suspension represents a
      potential route of amplification of early pregnancy signals from the embryo to
      influence the pattern of ovarian steroid secretion and perhaps that of
      folliculogenesis. Bearing in mind the relatively low concentration of hormones
      generated by the somatic cell suspension, vascular counter-current transfer of
      information is postulated from the Fallopian tube to the ipsilateral ovary.
      Molecular techniques are being applied as a means of examining endosalpingeal
      responses in four different experimental models in which the numbers and
      presumptive activity of suspended follicular cells are varied in pigs with
      spontaneous oestrous cycles. Because these animals ovulate on both ovaries,
      epithelial activity can be compared and contrasted between the two sides. In a
      final model, attempts are being made to generate early pregnancy responses in the
      absence of embryos by transplanting zygote-programmed cumulus cells from a mated
      donor into the Fallopian tube of an unmated recipient.

PMID- 16101040
TI  - Morphological and biochemical dynamics of porcine cumulus-oocyte complexes: role
      of cumulus expansion in oocyte maturation.
AB  - The process of cumulus expansion is a current topic of interest for in vitro
      production of embryos. In the present study, we examined the components of
      cumulus expansion, molecular mechanisms of cumulus expansion, and role of cumulus
      expansion for porcine oocyte maturation. The degree of cumulus expansion in the
      porcine cumulus-oocyte complexes (COCs) increased gradually until 48 h in culture
      in TCM-199. On the other hand, when the COCs were cultured in TCM-199 with a
      hyaluronan synthesis inhibitor and hyaluronidase, they showed no evidence of
      cumulus expansion during the culture period. Furthermore, the expression of
      hyaluronan synthase 2 (has2) in cumulus cells is accompanied by cumulus
      expansion. Hyaluronan receptor CD44 mRNA expressed in the cumulus cell, but not
      in the oocyte extracts. CD44 protein also expressed in/on the membrane of cumulus
      cells and its expression increased in a manner dependent on the degree of cumulus
      expansion. Moreover, we found that hyaluronan-CD44 system during cumulus
      expansion induces the activation of maturation promoting factor, resulting in
      germinal vesicle breakdown of the oocytes, and the tyrosine-phosphorylation of
      Cx43 in the COCs. The present results showed that the main component of cumulus
      expansion in the COCs is hyaluronan; the hyaluronan-CD44 system during cumulus
      expansion regulates the disruption of gap junctions in the COCs, and concurrently
      controls the incidence of meiotic resumption in the porcine oocytes.

PMID- 16101041
TI  - Cumulus oophorus extracellular matrix in the human oocyte: a role for adhesive
      proteins.
AB  - A viscous elastic matrix secreted by the cumulus oophorus cells represent the
      "extracellular matrix" surrounding the human mature oocyte obtained from assisted
      reproductive technology (ART). The cumulus matrix is involved in several
      reproductive processes, including the pick-up of the oocyte-cumulus complex by
      the oviduct, the final maturation of the ovum and sperm-egg interaction. As
      showed by some Authors, the cumulus matrix is rich in hyaluronan, as well as in
      other proteins including inter-alpha-trypsin inhibitor, a dermatan sulfate
      proteoglycan, and a pentraxin-3. Proteins and hyaluronan are linked together to
      form a meshwork comprised of granules and filaments. We found in human cumulus
      oocyte complexes the presence of specialized cells still capable of producing
      fibronectin and tenascin-c in the post-ovulatory period. Moreover, fibronectin
      and tenascin-c are present within the hyaluronan matrix at fertilization during
      the tubal sojourn of the ovum and the embryo. Since pentraxin3 is important in
      matrix stabilization and gamete interactions, a possible role for fibronectin and
      tenascin-c may be postulated in the final maturation of the ovum, in the tubal
      pick-up and in the complex dialogue with the tubal epithelium.

PMID- 16101042
TI  - Granulosa cell expression of basal lamina matrices: Call-Exner bodies and
      focimatrix.
AB  - A Call-Exner body appears as a rosette of granulosa cells radially disposed
      (polarized) around an aggregate of extracellular matrix. The function of these
      bodies is unknown. A newly described matrix, focimatrix, also develops as
      aggregates of basal lamina-like material between granulosa cells. It appears much
      later in follicular development, and in a far greater amount than Call-Exner
      bodies. Its possible role is to reduce the polarity of epithelial granulosa cells
      allowing them to develop into non-polarized mesenchymal luteal cells upon
      ovulation of the follicle. Call-Exner bodies may arise from early and isolated
      expression of focimatrix.

PMID- 16101043
TI  - Microscopical survey of the development and differentiation of the epithelium of
      the uterine tube and uterus in the human fetus.
AB  - The development and differentiation of the coelomic epithelium lining the
      paramesonephric ducts in human fetus, that gives rise to the female genital
      organs, have been ultrastructurally examined. The epithelium appeared
      pseudostratified, consisting of basal, microvillous and ciliated cells. In
      younger fetuses (12th gestational week) ciliogenic elements could be detected
      mainly on the developing tubal fimbriae, but most of the cells showed microvilli
      and often single cilia. In the subsequent phases of development, morphodynamics
      of cell renewal were documented by aspects of apoptosis. Fully ciliated cells
      were numerous on the fimbriae and at the utero-tubal junction, but not in the
      uterus; however, these were less abundant than those showing microvillous. In
      older fetuses (31st gestational week) microapocrine secretion by microvillous
      cells, in the form of droplets contacting cilia, could be observed. In the same
      fetuses the ectocervix was covered by a mature squamous epithelium, made up of
      polygonal flat desquamating cells, showing labyrinthine surface microplicae. Our
      observations demonstrated that ciliation in the human female genital organs, like
      that of other systems, is neither simultaneous nor uniform, and ciliated cells
      are gathered preferentially in strategic sites, to mediate germ cell migration
      and blastocyst implantation in adult life. These ultrastructural data seem to
      indicate that the female genital tract epithelium, at least in its general
      features, is sketched since fetal life, and cell morphodynamics, including
      microvillous and ciliated cell differentiation, as well as the secretory
      activity, are the morphological expression of the complex molecular mechanisms,
      involved in developmental biology and reproductive physiology.

PMID- 16101044
TI  - Pietro Motta's latest studies on the microanatomy of menopause: revised concepts
      on the beauty of aging.
AB  - Menopause signs a hallmark in women's life. When compared to traditional two
      dimensional techniques, scanning electron microscopy (SEM) allows to discover the
      impressive microcosm of the human body and offers original views of the real
      three-dimensional ultrastructure of reproduction. On the basis of Prof. Motta's
      last and original book, herein we show a selection of microscopic images that
      characterize the 3D changes taking place on the surface epithelia of the aging
      woman's reproductive tract. Biopsies of ovaries, tubes, uteruses, cervices and
      vaginas were obtained from women (45-72 years old) during surgical or
      endoscopical procedures and after the informed consent of the patients. Samples
      were processed for SEM as reported elsewhere. Reproductive aging is associated to
      epithelial flatness, higher stromal density, absence of ovarian follicles,
      thickening of vascular walls and lack of glandular secretion. The uterus and the
      tube show a morphodynamic sequence of gradual microvilli shortening, patchy to
      complete deciliation and formation of microplicae like structures. The formation
      of microplicae like structures is interpreted as an adaptive mechanical response
      of the genital epithelia to the new microenvironment. We can propose that these
      structures may represent the initial stage of a physiologic metaplasia. In
      conclusion, imaging of menopause through the use of SEM allows a better
      understanding of the morphological and physiopathological bases of female aging
      and represents a perfect blend of art and aesthetics: a further confirmation of
      the endless beauty of our inner microscopic anatomy.

PMID- 16101045
TI  - History of otorhinolaryngology (ORL) in different European countries between 1880
      and 1920.

PMID- 16101046
TI  - Development of otorhinolaryngology in Albania between 1880 and 1920.

PMID- 16101047
TI  - History of otorhinolaryngology in Austria from 1870 to 1920.

PMID- 16101048
TI  - Otolaryngology in Belarus between 1880 and 1920.

PMID- 16101049
TI  - History of Belgian otorhinolaryngology (ORL) 1880-1920.
AB  - In 1880, otorhinolaryngology was already established in Belgium. The
      establishment of ORL chairs in all four Belgian universities, the founding of a
      Scientific Society of Belgian Otorhinolaryngology and the appearance of
      outstanding figures and their extraordinary influence on Belgian
      otorhinolaryngology marked the period from 1880 to 1920. It was a period of
      'official recognition' of this speciality as a field in its own right, both in
      medicine and surgery.

PMID- 16101050
TI  - On the beginnings of otorhinolaryngology (ORL) in Bohemia and Moravia.

PMID- 16101051
TI  - Development of otorhinolaryngology (ORL) in Bulgaria for the period 1880-1920.

PMID- 16101052
TI  - Otorhinolaryngology (ORL) in Croatia between 1880 and 1920.

PMID- 16101053
TI  - Otorhinolaryngology (ORL) in Denmark 1880-1920.

PMID- 16101054
TI  - Historical development of otorhinolaryngology (ORL) in Estonia.

PMID- 16101055
TI  - History of otorhinolaryngology (ORL) in Finland from 1880 to 1920.

PMID- 16101056
TI  - Otorhinolaryngology (ORL) in France from 1880 to 1920.

PMID- 16101057
TI  - On the origins of the first German otorhinolaryngology (ORL) clinics.

PMID- 16101058
TI  - Development of otorhinolaryngology (ORL) in Great Britain 1880-1920.

PMID- 16101059
TI  - Development of otorhinolaryngology (ORL) in Greece between 1880 and 1930.

PMID- 16101060
TI  - Development of otorhinolaryngology (ORL) in Hungary between 1880 and 1920.

PMID- 16101061
TI  - Development of otorhinolarynogology (ORL) in Iceland from 1880-1920.

PMID- 16101062
TI  - Birth and development of otorhinolaryngology (ORL) in Italy.

PMID- 16101063
TI  - Development of otorhinolaryngology (ORL) in Latvia.

PMID- 16101064
TI  - Development of otorhinolaryngology (ORL) in Lithuania between 1880 and 1920.

PMID- 16101065
TI  - Contributions to the development of otorhinolaryngology (ORL) in the Netherlands
      between 1880 and 1920.

PMID- 16101066
TI  - Development of otolaryngology (ORL) in Norway between 1880 and 1920.

PMID- 16101067
TI  - Otolaryngology (ORL) at the turn of the 19th century in Poland - an historical
      review.

PMID- 16101068
TI  - Otorhinolaryngology (ORL) in Portugal 1880-1920.

PMID- 16101069
TI  - Otorhinolaryngology (ORL) in Romania between 1880 and 1920.

PMID- 16101070
TI  - Otorhinolaryngology (ORL) in Russia (before 1917) and the first ORL departments
      in Saint Petersburg.

PMID- 16101071
TI  - Development of otorhinolaryngology (ORL) in Serbia and Montenegro between 1880
      and 1920.

PMID- 16101072
TI  - Historical development of otolaryngology (ORL) in Slovenia between 1880 and 1920.

PMID- 16101073
TI  - Otorhinolaryngology (ORL) in Spain between 1880 and 1928.

PMID- 16101074
TI  - Swedish otorhinolaryngology (ORL) 1880-1920.

PMID- 16101075
TI  - History of otorhinolaryngology (ORL) in Switzerland between 1880 and 1920.

PMID- 16101076
TI  - Development of otorhinolaryngology (ORL) in Turkey between 1880 and 1920.

PMID- 16101078
TI  - Waiting for the results to come in.

PMID- 16101079
TI  - Happy midwives, happy mothers. Interview by Lynne Pearce.
AB  - A London obstetric hospital has bucked the trend of rising midwife vacancy rates
      by introducing flexible work patterns for its staff. Patients benefit from women
      centred care where midwives provide care throughout the pregnancy.

PMID- 16101080
TI  - With military precision.
AB  - Members of the volunteer reserve forces are currently providing nursing and
      medical assistance in Iraq. Employers are being urged to support their staff and
      recognise the skills they bring home.

PMID- 16101081
TI  - Teenage kick.

PMID- 16101085
TI  - Student attendance during college-based lectures: a pilot study.
AB  - AIM: To identify the factors that influence attendance and absenteeism among a
      group of second-year nursing students during the theory component of the Fitness
      for Practice (FFP) curriculum. METHOD: In 2004, a non-randomised questionnaire
      was used to elicit information about the factors surrounding absenteeism from 75
      adult branch nursing students within the first FFP cohort. The questionnaire
      consisted of 48 questions and was designed to generate a mixture of quantitative
      and qualitative data. Absence was recorded for the first 91 weeks of the
      programme. RESULTS: The main reasons identified for absence included: illness,
      family commitments, dental and medical appointments, and impending assignment
      submissions. Other factors that might influence college attendance included a
      dislike of certain subjects, with ethics, law and social policy identified as the
      least popular subjects. Students also admitted to an increase in absence around
      the time when assignments are due for submission and occasionally pretended to be
      ill. CONCLUSION: Further studies should be undertaken with other pre-registration
      nursing student cohorts to compare the results with this research. There should
      be: an increase in self-directed learning; a 'family-friendly' approach to the
      curriculum by allocating self-directed study during school holidays; a reduction
      in the number of theory hours to coincide with students' external commitments and
      to assist them with the demands of studying; and time for private study before
      the submission of theoretical assignments.

PMID- 16101086
TI  - Sun exposure and health.
AB  - This article discusses the current confusion regarding sun exposure. Having been
      told for many years to avoid the sun in an effort to prevent skin cancer, we are
      now being told that we may actually need to increase our exposure to sunlight to
      improve our health. Both sides of the debate are discussed and the information
      available is reviewed.

PMID- 16101087
TI  - Caring for the patient with an intestinal obstruction.
AB  - This article aims to increase your understanding of issues associated with
      intestinal obstruction, including the different causes of small bowel and large
      bowel obstruction, the treatments available and the best nursing management of
      patients with this condition.

PMID- 16101088
TI  - Assessing brain function.

PMID- 16101089
TI  - Inquiring minds.

PMID- 16101090
TI  - Jolly good fellow.

PMID- 16101091
TI  - Learn side by side.

PMID- 16101092
TI  - Six successful internal marketing strategies.

PMID- 16101093
TI  - Fibrin sealants in implant and periodontal treatment: case presentations.
AB  - Sutures are traditionally used to close flaps associated with periodontal and
      implant procedures. When implants are placed in the esthetic zone or when
      periodontal plastic surgical procedures are performed, fibrin sealants may be a
      viable alternative to closing flaps with sutures. This article describes the
      history of using fibrin sealants in medicine and dentistry and discusses their
      uses. Patients treated with sealants are presented.

PMID- 16101094
TI  - Conservatism and predictable dental esthetics.

PMID- 16101095
TI  - The osteotome technique: a classification for technique approach and clinical
      case reports.
AB  - A classification system for Summers' osteotome technique was proposed,
      categorizing the technique into 4 classes. Additional descriptions are included
      to further define different approaches. The classification for the technique
      approach will assist future communication among clinicians and researchers. This
      article presents representative clinical cases to aid the clinician in applying
      the classification for the technique approach.

PMID- 16101096
TI  - Looking beyond materials for clinical success.

PMID- 16101097
TI  - Current therapy: complications associated with rigid internal fixation of facial
      fractures.
AB  - Rigid internal fixation (RIF) is commonly used for the anatomical reduction and
      fixation of facial fractures. This technique has many advantages over more
      traditional methods, such as wire osteosynthesis and maxillomandibular fixation.
      Properly placed RIF ensures a stable anatomical reduction and allows for
      immediate or early restoration of function. RIF has a number of complications
      associated with its use in facial trauma surgery including metal sensitivity,
      infection, neurologic injury, dental trauma, stress shielding, and malocclusion.
      Complication rates appear to be inversely proportional with operator skill and
      experience when using RIF.

PMID- 16101098
TI  - Digital imaging/radiography: the future is here!

PMID- 16101099
TI  - Biodontics: Dental students as change agents for dental school curricula.

PMID- 16101100
TI  - The importance of CR.

PMID- 16101101
TI  - LED curing lights--what's new?
AB  - Technological changes to blue light-emitting diode (LED) light-curing units have
      taken place at an accelerated rate. The lighting industry, however, has not yet
      improved output levels of blue chip design used in dental LED units as quickly.
      In fact, the same 5 watt source has been offered since 1992. The next step in
      technology advancement is the use of conventional, contemporary chips with
      improved output levels. These levels may arise from supplying greater electrical
      power to the chip, and must be accompanied by designs that will reduce internal
      chip heat to avoid permanent damage. A new LED light design uses periodic level
      shifting (PLS) to intermittently increase chip output levels over those of
      baseline. In doing so, maximal output from the chip can be achieved, but not at
      the risk of destroying the source. This article describes the current state of
      LED light units, discusses the strategy of chip design and limitations, and
      presents a description of an LED recently introduced that uses PLS technology.

PMID- 16101102
TI  - Experimentation with animal models in space. Introduction.

PMID- 16101103
TI  - The hindlimb unloading rat model: literature overview, technique update and
      comparison with space flight data.
AB  - The hindlimb unloading rodent model is used extensively to study the response of
      many physiological systems to certain aspects of space flight, as well as to
      disuse and recovery from disuse for Earth benefits. This chapter describes the
      evolution of hindlimb unloading, and is divided into three sections. The first
      section examines the characteristics of 1064 articles using or reviewing the
      hindlimb unloading model, published between 1976 and April 1, 2004. The
      characteristics include number of publications, journals, countries, major
      physiological systems, method modifications, species, gender, genetic strains and
      ages of rodents, experiment duration, and countermeasures. The second section
      provides a comparison of results between space flown and hindlimb unloading
      animals from the 14-day Cosmos 2044 mission. The final section describes
      modifications to hindlimb unloading required by different experimental paradigms
      and a method to protect the tail harness for long duration studies. Hindlimb
      unloading in rodents has enabled improved understanding of the responses of the
      musculoskeletal, cardiovascular, immune, renal, neural, metabolic, and
      reproductive systems to unloading and/or to reloading on Earth with implications
      for both long-duration human space flight and disuse on Earth.

PMID- 16101104
TI  - International collaboration on Russian spacecraft and the case for free flyer
      biosatellites.
AB  - Animal research has been critical to the initiation and progress of space
      exploration. Animals were the original explorers of "space" two centuries ago and
      have played a crucial role by demonstrating that the space environment, with
      precautions, is compatible with human survival. Studies of mammals have yielded
      much of our knowledge of space physiology. As spaceflights to other planets are
      anticipated, animal research will continue to be essential to further reveal
      space physiology and to enable the longer missions. Much of the physiology data
      collected from space was obtained from the Cosmos (Bion) spaceflights, a series
      of Russian (Soviet)-International collaborative flights, over a 22 year period,
      which employed unmanned, free flyer biosatellites. Begun as a Soviet-only
      program, after the second flight the Russians invited American and other foreign
      scientists to participate. This program filled the 10 year hiatus between the
      last US biosatellite and the first animal experiments on the shuttles. Of the 11
      flights in the Cosmos program nine of them were international; the flights
      continued over the years regardless of political differences between the Soviet
      Union and the Western world. The science evolved from sharing tissues to joint
      international planning and development, and from rat postmortem tissue analysis
      to in vivo measurements of a host of monkey physiological parameters during
      flight. Many types of biological specimens were carried on the modified Vostok
      spacecraft, but only the mammalian studies are discussed herein. The types of
      studies done encompass the full range of physiology and have begun to answer
      "critical" questions of space physiology posed by various ad hoc committees. The
      studies have not only yielded a prodigious and significant body of data, they
      have also introduced some new perspectives in physiology. A number of the
      physiological insights gained are relevant to physiology on Earth. The Cosmos
      flights also added significantly to flight-related technology, some of which also
      has application on our planet. In summary, the Cosmos biosatellite flights were
      extremely productive and of low cost. The Bion vehicles are versatile in that
      they can be placed into a variety of orbits and altitudes, and can carry
      radiation sources or other hazardous material which cannot be carried on manned
      vehicles. With recent advances in sensor, robotic, and data processing
      technology, future free flyers will be even more productive, and will largely
      preclude the need to fly animal experiments on manned vehicles. Currently,
      mammalian researchers do not have access to space for an unknown time, seriously
      impeding the advancement and understanding of space physiology during long
      duration missions. Initiation of a new, international program of free flyer
      biosatellites is critical to our further understanding of space physiology, and
      essential to continued human exploration of space.

PMID- 16101105
TI  - Mouse infection models for space flight immunology.
AB  - Several immunological processes can be affected by space flight. However, there
      is little evidence to suggest that flight-induced immunological deficits lead to
      illness. Therefore, one of our goals has been to define models to examine host
      resistance during space flight. Our working hypothesis is that space flight crews
      will come from a heterogeneous population; the immune response gene make-up will
      be quite varied. It is unknown how much the immune response gene variation
      contributes to the potential threat from infectious organisms, allergic responses
      or other long term health problems (e.g. cancer). This article details recent
      efforts of the Kansas State University gravitational immunology group to assess
      how population heterogeneity impacts host health, either in laboratory
      experimental situations and/or using the skeletal unloading model of space-flight
      stress. This paper details our use of several mouse strains with several
      different genotypes. In particular, mice with varying MHCII allotypes and mice on
      the C57BL background with different genetic defects have been particularly useful
      tools with which to study infections by Staphylococcus aureus, Salmonella
      typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that
      some of these experimental challenge models will be useful to assess the effects
      of space flight on host resistance to infection.

PMID- 16101106
TI  - Vestibular experiments in space.

PMID- 16101107
TI  - Effect of space flight on circadian rhythms.

PMID- 16101108
TI  - Development as adaptation: a paradigm for gravitational and space biology.
AB  - Adaptation is a central precept of biology; it provides a framework for
      identifying functional significance. We equate mammalian development with
      adaptation, by viewing the developmental sequence as a series of adaptations to a
      stereotyped sequence of habitats. In this way development is adaptation. The
      Norway rat is used as a mammalian model, and the sequence of habitats that is
      used to define its adaptive-developmental sequence is (a) the uterus, (b) the
      mother's body, (c) the huddle, and (d) the coterie of pups as they gain
      independence. Then, within this framework and in relation to each of the
      habitats, we consider problems of organismal responses to altered gravitational
      forces (micro-g to hyper-g), especially those encountered during space flight and
      centrifugation. This approach enables a clearer identification of simple
      "effects" and active "responses" with respect to gravity. It focuses our
      attention on functional systems and brings to the fore the manner in which
      experience shapes somatic adaptation. We argue that this basic developmental
      approach is not only central to basic issues in gravitational biology, but that
      it provides a natural tool for understanding the underlying processes that are
      vital to astronaut health and well-being during long duration flights that will
      involve adaptation to space flight conditions and eventual re-adaptation to
      Earth's gravity.

PMID- 16101109
TI  - Use of animal models to study skeletal effects of space flight.

PMID- 16101110
TI  - Responses across the gravity continuum: hypergravity to microgravity.
AB  - In response to hypergravity, it appears that the larger the animal, the greater
      the response, if present. Therefore, the response of a rat exceeds that of a
      mouse in the same hypergravity environment. When investigated in the microgravity
      environment of space flight, this appears to hold true. The lack of definitive
      data obtained in space for either species makes the extrapolation of the
      continuum to levels below Earth-gravity problematic. However, in systems where
      responses are detected for both space flight and acceleration by centrifugation,
      a gravitational continuum is present supporting the "principle of continuity".
      For those and similar systems, it appears that the use of hypergravity could be
      used to predict responses to space flight.

PMID- 16101111
TI  - Gravity effects on life processes in aquatic animals.

PMID- 16101112
TI  - Primates in space flight.

PMID- 16101113
TI  - A computational model of conscious and unconscious strategy discovery.

PMID- 16101114
TI  - Out-of-school settings as a developmental context for children and youth.
AB  - Since the 1990s, there has been a growing recognition of the importance of the
      out-of-school context for children and adolescents. Fueled in part by family
      demographics that include substantial numbers of employed mothers and single
      mothers, in part by concerns about poor academic performance and problem
      behaviors, and in part by intensified efforts to find ways to promote positive
      youth development, researchers and practitioners have focused their attention on
      two particular out-of-school settings: after-school programs and structured
      activities. The research findings pertaining to full-time (i.e., 5 days a week)
      after-school programs are mixed, which may reflect the substantial heterogeneity
      of the programs in terms of children being served, the types of activities
      offered, and the training and background of the staff. The federal funding of the
      21st Century CLCs and various state and local initiatives has increased the
      numbers of low-income and English-learning students participating in after-school
      programs. A substantial number of programs are becoming more school-like. The
      available research suggests that (under some conditions) attending after-school
      programs is linked to improved social and academic outcomes. Children are more
      likely to show academic and social benefits when staff-child relationships are
      positive and nonconflictual, when programs offer a variety of age-appropriate
      activities from which children can select those of interest, and when children
      attend on a regular basis. The research findings about voluntary structured
      activities are more straightforward. Participation in these activities has been
      consistently linked to positive academic and social developmental outcomes in
      numerous studies. What appears to be key is that the activities are voluntary,
      are characterized by sustained engagement and effort, and provide opportunities
      to build or develop skills. Although the available research has begun to inform
      our understanding of the out-of-school context, further research is sorely
      needed. First, there is a need for research to identify the social, cognitive,
      and linguistic processes by which participation in programs and structured
      activities influences child and youth developmental outcomes. For example,
      researchers need to consider the competitiveness of sport activities in relation
      to children's social and emotional functioning. Researchers also might examine
      after-school experiences as settings in which complex thought processes can
      develop. Heath (1999) has conducted initial work in the area of language
      development by obtaining language samples during voluntary structured activities
      and analyzing their content. In the initial samples, students engaged in few
      sustained conversations on a topic and they frequently changed topics. After 3-4
      weeks at the program, however, Heath noted substantial changes in the students'
      conversations and language. The use of conditionals (should, would, could)
      increased. She also noted increases in strategies to obtain clarifications from
      others and increases in the use of shifted registers and genres. Heath's (1999)
      linguistic analyses in conjunction with research that considers social and
      motivational processes underscore the broader point that the out-of-school
      context is complex and multi-layered and likely to be of substantial importance
      in the lives of children and youth. Research is needed to identify other
      important developmental processes in programs and structured activities. A
      promising procedure for identifying these processes is experience sampling
      (Csikszentmihalyi & Larson, 1987; Larson, 1989). Experience sampling methodology
      allows researchers to collect systematic data about an individual's activities,
      thoughts, and affective states by obtaining reports from participants at multiple
      randomly sampled points in time. Participants are signaled to provide a report in
      a variety of ways, such as with beepers or alarm watches. This record of
      experiences is not usually captured by other data collection methods. For
      example, program observations provide data on observed activities, interactions,
      and program climate, but do not offer insights into students' feelings and
      experiences within the after-school environment. Questionnaire and survey data
      are retrospective, asking respondents to recall past experiences and feelings
      regarding their after-school activities. Experience sampling could be used to
      examine any number of processes in after-school programs and structured
      activities. A better understanding of the effects of program content also is
      needed. Whether after-school programs should focus exclusively on enrichment
      activities or exclusively on academic activities, or include both enrichment and
      academic components, is the subject of heated debate. Some after-school scholars
      (Halpern, 1999; Heath, 1999; Eccles, in press) have argued forcefully that a
      focus on academics undermines the unique strengths and role of programs, and that
      programs should emphasize extracurricular enrichment activities. Others (Noam,
      2004) have supported the move by policy makers and educators to make programs
      more academic, with an emphasis on homework help, tutoring, and preparation for
      academic achievement tests. The effects of different approaches to after-school
      programming have not been evaluated systematically. Research that describes,
      compares, and then tests effects of different program content models is needed to
      determine which types of programs are successful in attracting and keeping
      students (a necessary condition for programs to effect change), and to determine
      whether different types of programs are differentially associated with
      improvements in student outcomes such as school attendance, academic achievement,
      social competencies, and behavioral adjustment. A related question is whether
      structured activities that are obligatory or required have the same effects as
      voluntary structured activities do. Researchers also should further examine the
      impact of different attendance patterns on child developmental outcomes. We do
      not have solid information about optimal intensity and duration of attendance in
      terms of outcomes. There are suggestions in the literature that long-term,
      frequent attendance at programs is associated with positive outcomes for low
      income children. Research needs to examine whether these results hold for middle
      income children and youth as well. Finally, experimental studies should be
      conducted in which children and adolescents are randomly assigned to after-school
      programs and structured activities. All of the research to date on structured
      activities, and most of the research on after-school programs, has been
      nonexperimental, so questions about selection bias remain. Experimental studies
      in which children and adolescents are randomly assigned to participation in
      programs and activities would be a valuable next step in understanding relations
      between participation and child and youth outcomes. Such research should not be
      conducted until we have more information about the components of high-quality
      programming in terms of program content and developmental processes, however.

PMID- 16101115
TI  - Mechanisms of change in the development of mathematical reasoning.

PMID- 16101116
TI  - A social identity approach to ethnic differences in family relationships during
      adolescence.

PMID- 16101117
TI  - What develops in language development?

PMID- 16101118
TI  - The role of children's competence experiences in the socialization process: a
      dynamic process framework for the academic arena.

PMID- 16101119
TI  - The infant origins of intentional understanding.

PMID- 16101120
TI  - Analyzing comorbidity.

PMID- 16101121
TI  - Number words and number concepts: the interplay of verbal and nonverbal
      quantification in early childhood.

PMID- 16101122
TI  - Chitinase induces lysis of MCF-7 cells in culture and of human breast cancer
      xenograft B11-2 in SCID mice.
AB  - BACKGROUND: It has long been known that the polycarbohydrates on the neoplastic
      cell surface are different from those on normal cells; differences which allow
      one to attack tumor cells selectively. Although the exact differences between
      tumor cells and normal cells are still not clearly known, research into these
      differences is ongoing for anticancer drug development. MATERIALS AND METHODS:
      The human breast cancer cell line MCF-7 in culture and human breast xenograft
      B(11)-2 in SCID mice were used in our observations. Two different samples of
      chitinase from different bacteria were tested in the experiments. Optical
      observation of regular H & E-stained tumor tissue sections and observations by
      transmission electron microscopic techniques were used in this study. RESULTS:
      MCF-7 breast cancer cells in culture showed structural damage within 7 hours
      after 1.3 unit/ml of chitinase was added to the medium, while normal mice spleen
      cells did not. The transplanted B(11)-2 xenograft tissue in mice started to lyse
      12 hours after chitinase was injected; the size of the tumor gradually reduced
      and finally a scab was formed, which came off the skin a few days later. All the
      tested tumor-bearing mice survived and these cured mice had no tumor re-growth
      during the following 1-year observation period. CONCLUSION: Chitinase selectively
      lysed the tumor cells in vitro and in vivo. Injected chitinase destroyed the
      tumor tissue and cured the mice. The further development of this type of
      treatment and of the mechanisms of chitinase action are discussed.

PMID- 16101123
TI  - Inhibition of MRP1-mediated efflux in human erythrocytes by mono-anionic bile
      salts.
AB  - BACKGROUND: Multidrug resistance-associated protein 1 (MRP1 or ABCC1) -mediated
      transport is an important mechanism in multidrug resistance during cancer
      treatment. One strategy for the reversal of MRP1-mediated multidrug resistance is
      inhibition of this efflux pump. Therefore, efficient inhibitors are searched for
      and the structure-activity relationships of inhibitors are studied. In the
      present work, the ability of a series of mono-anionic bile salts to inhibit MRP1
      like substrate transport was examined. MATERIALS AND METHODS: The effect of bile
      salts on the efflux of the MRP1 substrate 2,7'-bis-(carboxypropyl)-5(6)
      carboxyfluorescein (BCPCF) from human erythrocytes was fluorimetrically
      monitored. RESULTS: All bile salts inhibited the BCPCF efflux. The most efficient
      inhibitor, lithocholic acid, decreased the BCPCF efflux by 50% (IC50) at 4 microM
      during 60 min of incubation at 37 degrees C. The most efficient bile salt
      inhibitors showed high haemolysis start/IC50 concentration ratios and did not
      induce membrane bending or phosphatidylserine (PS) exposure at IC50. CONCLUSION:
      The overall hydrophobicity, as well as the orientation of the hydroxyl groups and
      conjugation with glycine or taurine per se, affect the inhibitory potency of bile
      salts. The most efficient inhibitors apparently interact with MRP1 in a specific
      way.

PMID- 16101124
TI  - Characterization of IGH rearrangements in non-Hodgkin's B-cell lymphomas by
      fluorescence in situ hybridization.
AB  - Rearrangements involving the IGH gene have been identified in about 50% of non
      Hodgkin's B-cell lymphomas (NHL) and correlated to clinical relevant subgroups.
      However, the detection rate varied greatly with the technique used. The incidence
      of IGH rearrangements was analyzed using several fluorescence in situ
      hybridization (FISH) techniques on metaphases obtained from 57 patients with
      nodal NHL. An IGH rearrangement was identified in 42 cases (73.7%). A
      t(14;18)(q32;q21) was found in 17 of the 20 follicular lymphomas (85%) studied
      and a t(11;14)(q13;q32) in 10 of the 11 mantle cell lymphomas (91%). IGH
      rearrangements were identified in 12 of the 26 diffuse large B-cell lymphomas
      (46%), including 5 t(14;18)(q32;q21) and 2 t(3;14)(q27;q32). Conventional
      cytogenetics was uninformative in several cases. However, the complemented
      analysis using Multi-FISH and/or chromosomal whole paint enabled the
      characterization of complex IGH translocations in follicular lymphomas and mantle
      cell lymphomas and the identification of all the chromosomal partners involved in
      the IGH rearrangement in diffuse large B-cell lymphomas. This study shows the
      interest of using metaphase FISH in addition to conventional cytogenetics.
      Following banding techniques, FISH with the IGH dual color probe could be the
      first approach in NHL, after which chromosome painting and M-FISH could be used
      to identify the chromosomal partner involved in the IGH rearrangement.

PMID- 16101125
TI  - Soft and hard keratin expression in Epstein-Barr-virus-associated gastric
      carcinoma.
AB  - BACKGROUND: Epstein-Barr-virus-associated gastric carcinoma (EBVaGC) is a
      distinct subset of gastric carcinoma (GC). The expressions of cytokeratins (CK)7,
      8, 18, 19 and 20 and truncated basic hair keratin 1 (hHb1-deltaN) were
      investigated in GC to clarify the characteristics of EBVaGC. MATERIALS AND
      METHODS: For immunohistochemical evaluation, 173 GC tissues were examined and 31
      GC tissues and 5 GC cell lines were used for quantitative real-time RT-PCR (qrt
      RT-PCR) and RT-PCR. RESULTS: EBVaGC showed significantly lower
      immunohistochemical positivity of CK7 (-/(+/-)/+/+ +/+ + +; 27/15/4/1/1) compared
      to EBV-negative GC (12/29/27/44/13), even after stratification by histological
      types. The qrt-RT-PCR test demonstrated decreased amounts of CK7, 18 and 19 mRNAs
      in EBVaGC. Two among 5 GC cell lines showed a decrease of CK7 mRNA level after
      recombinant EBV infection. hHb1-deltaN expression was not specific to EBVaGC.
      CONCLUSION: Abnormalities of CK7, 18 and 19 expressions, especially a decreased
      amount of CK7 expression, are characteristics of EBV-associated epithelial
      malignancies and might be important in carcinogenesis.

PMID- 16101126
TI  - Mice transgenic for NPM-ALK develop non-Hodgkin lymphomas.
AB  - BACKGROUND: The t(2;5)(p23;q35) translocation is associated with a high
      percentage of anaplastic large-cell lymphomas (ALCL) of T- or null-cell
      phenotype. The translocation produces an 80 kDa hyperphosphorylated chimeric
      protein (p80) derived from the fusion of the anaplastic lymphoma kinase (ALK)
      with nucleophosmin (NPM). The NPM-ALK chimeric protein is an activated tyrosine
      kinase that has been shown to be a potent oncogene and presumably plays a
      causative role in lymphomagenesis. MATERIALS AND METHODS: A transgenic mouse line
      was generated, where the human NPM-ALK cDNA is driven by the lck promoter
      conferring transgene expression to early T-cells. RESULTS: Mice rapidly developed
      large cell lymphoblastic lymphomas with a median latency of 8 weeks, primarily
      involving the thymus, with lymph node as well as histologically evident
      extranodal organ infiltration by large tumor cells. CONCLUSION: The transgenic
      approach described provides direct evidence for the strong transforming potential
      of NPM-ALK in T-cells and furthermore represents a system for the analysis of the
      oncogenic events mediated by NPM-ALK in vivo, which might be instrumental in the
      development of tyrosine kinase inhibitor therapies of potential clinical use.

PMID- 16101127
TI  - The influence of high doses of vitamin C and zinc on oxidative DNA damage.
AB  - BACKGROUND: The influence of interactions between reactive oxygen species (ROS)
      and dietary antioxidants and their influence on cancer is not clear. It is
      believed that this effect is mediated by decreased oxidative damage to DNA. The
      aim of this study was to further investigate the in vitro DNA protective or
      damaging effects of dietary antioxidants using the single cell gel
      electrophoresis (Comet) assay. MATERIALS AND METHODS: Stimulated and unstimulated
      lymphocytes of 10 individuals were cultured with and without different
      concentrations of vitamins C and zinc and damaged with H2O2. RESULTS: DNA damage
      measured by Olive tail moment in the Comet assay showed a non-significant trend
      to reduce DNA strand breaks at low vitamin and trace element concentrations. At
      higher vitamin C and zinc doses, DNA damage was significantly increased.
      CONCLUSION: The in vitro data of the present study suggest that high dosage
      intake of vitamin C and zinc may cause more harm than benefit. There is good
      evidence that health-related effects of dietary antioxidants strongly depend on
      individual genetic susceptibilities and health status.

PMID- 16101128
TI  - Characterization of the 20S proteasome in human glioblastomas.
AB  - Proteasomes are multisubunit proteases involved in many cellular processes,
      including tumorigenesis and immune surveillance. In their catalytic core, the 20S
      proteasome, the beta1, beta2 and beta5 subunits show peptidylglutamyl peptide
      hydrolyzing (PGPH), trypsin-like and chymotrypsin-like activities, respectively.
      By IFN-gamma and TNFalpha stimulus, these subunits are replaced by their
      counterparts LMP2, MECL-1 and LMP7, defined inducible subunits, thus originating
      the immunoproteasome, and expression of the proteasome activator PA28 is
      enhanced. These modifications strengthen MHC-class I restricted peptide
      generation. The 20S proteasome has been detected immunohistochemically in
      formalin-fixed samples purified from fresh surgical specimens of 18 tumors (G20S)
      and from 8 samples of normal peritumoral tissue. The G20S, LMP2, MECL-1 and LMP7
      increased in only 12 cases, along with unvaried trypsin-like and decreased PGPH
      and chymotrypsin-like activities; PA28 was unvaried in all 18 samples. The
      immunoproteasome alterations may represent an anomalous immunological attitude of
      glioblastomas.

PMID- 16101129
TI  - Antibodies to cerebellar nerve fibres in two patients with paraneoplastic
      cerebellar ataxia.
AB  - The aim of this study was to characterize two new atypical anti-neuronal
      antibodies using an immunohistochemical method on rat cerebellum and Western blot
      techniques with primate cerebellar tissue and with recombinant neuronal proteins.
      Atypical sera from two patients with paraneoplastic neurological syndromes
      associated with different tumours were detected. Case number 1 presented
      cerebellar degeneration and Merkel cell carcinoma and case number 2
      paraneoplastic brainstem encephalitis and malignant fibrous histiocytoma. By
      immunohistochemistry, the two new atypical antibodies showed a similar fibrillar
      positivity in the molecular and granular layers and around the Purkinje cells.
      The dot blot with recombinant neuronal proteins (HuD, NOVA-1, CDR62/Yo,
      Amphiphysin) was negative, whereas the Western blot with neuronal antigens of
      primate cerebellum identified two different proteins with molecular weights (64
      kD in case number 1, and 70 kD in case number 2). In conclusion, the two new
      antibody reactivities against nerve fibres should be integrated into the
      diagnostic paraneoplastic neurological syndromes guidelines.

PMID- 16101130
TI  - Biomarkers of anticancer activity of R115777 (Tipifarnib, Zarnestra) in human
      breast cancer models in vitro.
AB  - BACKGROUND: Farnesyltransferase inhibitor R115777 (Tipifamib, Zarnestra) is
      active in breast cancer, but its efficacy in drug combinations has not been
      extensively investigated. MATERIALS AND METHODS: The activity of R115777 and
      paclitaxel, alone and in combination, was studied in the human breast cancer cell
      lines, BT-474 (overexpressed HER2/neu) and MDA-MB-231 (low HER2/neu), with cell
      viability and biomarkers for farnesylation (HDJ-2, Rho B), tumor growth
      (Raf/MEK/ERK), survival (PI3K/Akt) and angiogenesis (VEGF, FGF-2, MMP-1, MMP-2,
      MMP-9) as the endpoints. RESULTS: The drug combination resulted in additive
      cytotoxicity. R115777 +/- paclitaxel inhibited HDJ-2 farnesylation, up-regulated
      RhoB, transiently lowered (P)ERK/ERK and (P)Akt/Akt, reduced Raf-1 and MEK and
      inhibited secretion of VEGF and MMP-1. CONCLUSION: The effect of R115777 on
      prenylation biomarkers is consistent with its mechanism of action. The drug
      interfered with tumor growth, survival and angiogenesis pathways in breast cancer
      models with low or overexpressed HER2/neu receptor. The combination of R115777
      with paclitaxel might offer clinical advantage over monotherapies.

PMID- 16101131
TI  - Increased expression of interleukin-1alpha and cyclooxygenase-2 in human gastric
      cancer: a possible role in tumor progression.
AB  - BACKGROUND: Cyclooxygenase (COX)-2 mRNA and protein expression have been found to
      be frequently up-regulated in human gastric cancers and cell lines. COX-2 is the
      inducible form of COX, and interleukin (IL)-1alpha may be one of the stimulators
      of COX-2. MATERIALS AND METHODS: The relationship between IL-1alpha and COX-2
      expression was examined in human gastric cancer tissues and cell lines. RESULTS:
      IL-1alpha mRNA was expressed in 19 out of 32 human gastric cancer specimens
      (60%), while it was not expressed in any of the paired normal gastric mucosa
      specimens. The incidence of IL-1alpha mRNA expression was significantly higher in
      patients with pT2-pT4 tumors than in those with pT1 tumors (86% vs. 39%, p<0.05).
      IL-1alpha mRNA was expressed in 94% of COX-2-positive tumors, while it was
      expressed in only 25% of COX-2-negative tumors (p<0.0001). When IL-1alpha was
      added to the medium of gastric cancer cell lines (MKN28 and MKN45), it enhanced
      the expression of IL-1alpha itself and COX-2 mRNA in both cell lines. Exogenous
      IL-1alpha stimulated cancer cell growth in both cell lines, while such growth
      stimulation was suppressed by anti-IL-1alpha antibody or IL-1 receptor
      antagonist. IL-1alpha-stimulated cell growth was also suppressed by anti-COX-2
      antibody. CONCLUSION: Our data demonstrated that IL-1alpha and COX-2 mRNA were
      frequently co-expressed in human gastric cancer tissues, and suggested that the
      IL-1alpha-COX-2 pathway might be involved in tumor progression by regulating
      cancer cell proliferation.

PMID- 16101132
TI  - Serum p53 antibodies in drainage blood from the azygos vein in patients with
      esophageal carcinoma.
AB  - BACKGROUND: Serum p53 antibodies (p53-Ab) have been detected in some cancers. The
      possible correlation between serum p53-Ab levels in drainage blood from the
      azygos vein in patients with esophageal carcinoma and prognosis was investigated.
      MATERIALS AND METHODS: Serum p53-Ab levels were examined in both the peripheral
      and azygos veins of 57 patients, and in the peripheral vein of 17 healthy
      volunteers. Serum p53-Ab levels were measured using an enzyme-linked
      immunosorbent assay. RESULTS: The positive rate of serum p53-Ab in the peripheral
      vein of the patients was 31.6%, significantly higher than that of the normal
      volunteers. There were no significant correlations between the
      clinicopathological features and the serum p53-Ab in either the peripheral or
      azygos veins. Serum p53-Ab levels in either vein did not correlate with prognosis
      in the univariate survival analysis, although the levels in the two veins were
      significantly correlated. CONCLUSION: Serum p53-Ab levels in the azygos vein did
      not reflect the tumor status or prognosis more directly or accurately than those
      in the peripheral vein, since levels in the two veins were similar. Therefore,
      measurement of serum p53-Ab in the azygos vein does not appear to be necessary.

PMID- 16101133
TI  - Alpha- and beta-tubulin expression in rectal cancer development.
AB  - BACKGROUND: Microtubules are involved in cell growth and division, motility,
      signalling and in the development and maintenance of cell shape. Consequently,
      the non-equilibrium dynamics of these microtubules can be crucial to cellular
      function, including cancer development. Although the involvement of tubulins in
      human development has been well investigated, the role of alpha- and beta
      tubulins in human tumorigenesis still remains controversial. The aim of this
      study was to investigate alpha- and beta-tubulin protein expression in rectal
      cancer development. PATIENTS AND METHODS: By immuno-histochemistry, using alpha-
      and beta-tubulin monoclonal antibodies, 66 patients were examined, 32 of whom (22
      male, 10 female; range 31-60 years, mean age 49.5 years) had preneoplastic
      lesions discovered during endoscopic surveillance, which were classified as mild,
      moderate and severe dysplastic polyps of the rectum, and 34 had invasive
      adenocarcinomas (24 male, 10 female; range 39-60 years, mean 52 years) of the
      rectum, with no local or distant metastases at the time of surgical resection.
      RESULTS: In preneoplastic lesions, no statistically significant relationship was
      found among alpha- and beta-tubulin protein expression, grade of dysplasia, or
      other clinical data. Statistical association among alpha- and beta-tubulin
      immunoreactivity and Dukes' stages B and C was found with p = 0.017 and p =
      0.009, respectively. No statistical relationship was found between alpha- and
      beta-tubulin protein expression among different grades of dysplasia. On the
      contrary, a significant relationship was detected among tubulins in different
      stages of cancer. CONCLUSION: In this preliminary study a significant difference
      of alpha- and beta-tubulin protein expressions was found in polyps and invasive
      cancer of the rectum, indicating a possible role of tubulins in invasive, but not
      in preinvasive cancer development. This preliminary data suggest the possibility
      of performing alpha- and beta-tubulin protein expression in order to identify B
      stage versus C stage rectal cancer, before surgical treatment.

PMID- 16101134
TI  - Differential diagnosis and evaluation of the clinical course of transurethrally
      resected T1G3 urothelial carcinoma of the bladder by DNA image cytometry.
AB  - The value of DNA image cytometry in the differential diagnosis of 106 T1G3
      urothelial carcinomas of the bladder and the long-term prognosis (recurrence-free
      interval, survival) of the patients was tested in comparison with Ta/T1G1 (n=30)
      and Ta/T1G2 carcinoma (n=54). Monolayer smears were prepared from three 50-microm
      thick sections by a cell separation technique and were stained according to
      Feulgen. The DNA content of 250 epithelial cells, chosen at random, was
      determined using a TV-image analysis system CM-1 (Hund, Wetzlar, Germany). The
      DNA content of 30 lymphocytes served as an internal standard for the normal
      diploid value in every individual case. Different DNA cytometric parameters and
      the mean nuclear area were calculated. In comparison with G1- and G2-cases, the
      mean values of all DNA cytometric variables were markedly increased in the group
      of T1G3 cases, most obviously for the 5cEE, the mean ploidy and the ploidy
      imbalance (0.0006 > or = p > or = 0.0001). However, a remarkable overlay of the
      data distribution had to be considered. An aneuploid DNA stemline ploidy was
      highly characteristic for T1G3 urothelial carcinoma (sensitivity: 92%), but not
      sufficiently specific (57%). However, if increased values for the mean ploidy,
      the 2cDI, the 5cEE or the 9cEE (specificity: 86%-89%) were present additionally,
      the diagnosis of a T1G3 urothelial carcinoma could be made cytometrically. Follow
      up data for survival (recurrence) analysis was available for 90 (82) patients of
      the T1G3 group. Using the median value as threshold, significant differences in
      survival were found for the mean ploidy only (p=0.0353). The length of the
      recurrence-free interval was significantly different for the entropy (p=0.0205),
      the 2cDI (p=0.0309) and the mean ploidy (p=0.0442). In conclusion, DNA single
      cell cytometry represents a highly relevant tool in the objective identification
      of T1G3 urothelial carcinoma of the bladder, with a sufficient sensitivity and
      specificity. Further, this method enables prediction of tumor recurrence if
      suitable variables are chosen. The long-term survival of patients with T1G3
      urothelial carcinoma can be estimated by DNA cytometry only in a limited manner,
      possibly due to the fact that the causes of death in the mostly elderly patients
      will be independent from the limited tumor disease.

PMID- 16101135
TI  - A new method for optimizing multiplex DNA microsatellite analysis in low quality
      archival specimens.
AB  - BACKGROUND: Testing microsatellite instability seems to be a useful tool for the
      initial screening of putative non-polyposis colorectal cancer (HNPCC), preceding
      analysis of germ-line mutations of DNA mismatch repair genes. However, diagnosis
      of microsatellite instability becomes complicated when highly-damaged DNA from
      formalin-fixed paraffin-embedded tissue specimens has to be investigated.
      MATERIALS AND METHODS: A new methodical approach was established based on special
      multiplex PCR regimes (e.g., on touch-up cycling conditions), allowing both
      sufficient, as well as specific, amplification of the Bethesda reference panel
      loci with low quality DNA as template. RESULTS: By applying our new method,
      microsatellite instability could be analyzed successfully in 75 out of 84
      investigated tumors (89%), whereas, by using standard PCR protocols,
      microsatellite analysis failed in 36% of the investigated cases. CONCLUSION: Our
      new methodical approach should be recommended for the use of archival material
      since it allows an efficient and accurate amplification of the Bethesda marker
      fragments and is less dependent on the DNA quality.

PMID- 16101136
TI  - Inhibition of P-glycoprotein transport activity in a resistant mouse lymphoma
      cell line by diterpenic lactones.
AB  - Multidrug resistance (MDR) is believed to be a major reason for the failure of
      cancer treatment. It is in most cases caused by the activity of the various ABC
      transporters, multidrug resistance (MDR) gene-encoded p-glycoproteins that pump
      anticancer drugs out of the cells. P-glycoprotein (P-gp) and multidrug resistance
      associated protein (MRP1) are the most important and widely studied members of
      the ABC superfamily of transporters. The ability of four diterpenic lactones
      isolated from Euphorbia species to modulate the transport activity of P-gp in
      mouse lymphoma cells was evaluated by flow cytometry. The reversion of MDR was
      investigated by using a standard functional assay with rhodamine 123 as a
      fluorescent substrate analogue of doxorubicin. Verapamil was applied as a
      positive control. All the compounds were able to reverse the MDR of the tested
      human MDR1 gene-transfected mouse lymphoma cells, in a concentration-dependent
      manner from 4 to 40 microg/mL, in a short-term experiment below the cytotoxic
      doses.

PMID- 16101137
TI  - Induction of cytotoxicity and apoptosis and inhibition of cyclooxygenase-2 gene
      expression by eugenol-related compounds.
AB  - Induction of cytotoxicity and internucleosomal DNA fragmentation by 4-allyl-2
      methoxyphenol (eugenol, EUG), 2-methoxy-4-methylphenol (MMP), 3,3'-dimethoxy-5,5'
      di-2-propenyl-1,1'-biphenyl-2,2'-diol (bis-EUG) and 3,3'-di-methoxy-5,5'-dimethyl
      1,1'-biphenyl-2,2'-diol (bis-MMP) were investigated in HL-60 leukemia cells. The
      50% cytotoxic concentrations (CC50) for EUG, MMP, bis-EUG and bis-MMP were 0.38
      mM, 0.38 mM, 0.18 mM and 0.20 mM, respectively. DNA fragmentation was induced
      most strongly by bis-EUG, followed by EUG, MMP and bis-MMP. The expression of
      MnSOD and, less strongly, Cu/ZnSOD activity, as assessed by acrylamide gel
      electrophoresis, was inhibited by EUG, suggesting mitochondrial dysfunction. The
      expression of the mRNAs for MnSOD and Cu/ZnSOD in HL-60 cells, as assessed by RT
      PCR, was significantly inhibited by treatment with 1 mM EUG for 1 hour.
      Furthermore, inhibition of SOD mRNAs expression by EUG was strongly potentiated
      by the addition of 5 mM N-acetyl cysteine (NAC) or glutathione (GSH), whereas NAC
      or GSH alone did not affect the expression of SOD mRNAs. The cytotoxicity of EUG
      was significantly enhanced by high concentrations of NAC or GSH, which may be
      attributed to the inhibition of SOD mRNAs expression by the synergistic action of
      EUG and GSH or NAC. The regulatory effects of eugenol-related compounds on
      lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2) gene expression in RAW
      264.7 cells were investigated by Northern blot analysis. Bis-EUG, MMP and bis-MMP
      inhibited COX-2 gene expression at concentrations of 300 microM, 500 microM and
      500 microM, respectively. In contrast, no inhibitory effect of EUG was found over
      the wide concentration range of 10-500 microM, possibly as a result of the
      extensive mitochondrial dysfunction induced by this compound, which possesses
      potent pro-oxidative activity. Eugenol-related compounds, particularly bis-EUG,
      may act as nonsteroidal anti-inflammatory drug (NSAID)-like compounds.

PMID- 16101138
TI  - 5-Fluorouracil up-regulates interferon pathway gene expression in esophageal
      cancer cells.
AB  - 5-Fluorouracil (FU) is a chemotherapeutic agent commonly used against esophageal
      cancer. Recently, interferons (IFNs) have been administered together with
      cytotoxic chemotherapy to patients with this cancer, although the mechanisms of
      synergy are unknown. We reconsidered the mechanisms for the effects of 5-FU in
      this context, aiming to refine combination therapy. After three cell lines (T.T,
      TE-2, and TE-6), derived from human esophageal squamous cell carcinoma (SCC),
      were exposed to 5-FU, the expression profiles were analyzed using high-density
      oligonucleotide microarrays representing about 12,000 genes. Among them, three
      IFN-related genes, an IFN receptor gene (IFNAR2) and two IFN-stimulated genes
      (ISG15K, ISG-54K), that were up-regulated following addition of 5-FU, were
      investigated. Up-regulation was confirmed by RT-PCR. Based on these results, the
      antitumor effects of exposure to 5-FU simultaneously with IFN-alpha, -beta and 
      gamma were investigated. The growth of esophageal SCC cells with 5-FU was
      suppressed synergistically or semi-additively by IFN-alpha and -beta, but not by
      IFN-gamma. These findings indicated that 5-FU stimulated IFN pathways in
      esophageal SCC cells following up-regulation of the IFN type I receptor. A
      combination of 5-FU and an IFN, therefore, may be particularly efficacious in
      esophageal cancer.

PMID- 16101139
TI  - Reversal of hepatoma cells resistance to anticancer drugs is correlated to cell
      proliferation kinetics, telomere length and telomerase activity.
AB  - BACKGROUND: Clinical and experimental observations indicate that resistance to
      anticancer drugs may be spontaneously reversible over time. MATERIALS AND
      METHODS: This work is a mathematical and statistical analysis of the
      relationship, during a 9-month experiment, between the resistance of repeatedly
      re-seeded hepatoma cells to methotrexate (MTX) or to cisplatin (cisP) and
      untreated cell proliferation, telomere length and telomerase activity. RESULTS:
      All variables showed complex oscillations, as previously published. In this work,
      cell proliferation was modelized by the logistic model, and the proliferation
      rates (a-values) together with their variations (va-values) were calculated.
      CONCLUSION: Significant correlations were discovered between cell resistance to
      treatments and a-values, va-values, telomere length and telomerase activities.
      These results open new insights into the handling of chemotherapy in the
      treatment of cancers.

PMID- 16101140
TI  - Circulating vascular endothelial growth factor and interferon-gamma-inducible
      protein-10 levels in pancreatic cancer during chemotherapy.
AB  - BACKGROUND: Chemotherapeutic anticancer properties are thought to derive from
      apoptosis pathway activation and/or cell division arrest, but animal models have
      also evidenced anti-angiogenic activity in some agents. PATIENTS AND METHODS: The
      impact of gemcitabine, irinotecan and oxaliplatin + 5-FU upon the serum markers
      vascular endothelial growth factor (VEGF) (pro-angiogenic) and IFN-gamma
      inducible protein (IP)-10 (anti-angiogenic) was evaluated by ELISA in locally
      advanced and/or metastatic cancer versus clinical efficacy and survival. RESULTS:
      Patients had higher serum levels of both markers versus controls. No objective
      response to therapy was observed and no significant difference in either marker
      occurred during the first month of chemotherapy; analysis by survival showed
      slight transient VEGF decrease in longer survivors on day 14 and slight increase
      on day 28 in shorter survivors, who had baseline median IP-10 levels above longer
      survivors, diverging on day 14 (decrease and increase, respectively). Both groups
      were below baseline at day 28. Changes in IP-10 were not significant. CONCLUSION:
      These preliminary results provide a rationale for exploring whether continuous or
      frequent administration of some anti-neoplastic agents may elicit a global anti
      angiogenic activity, and whether different administration schedules of the same
      drug could have a synergistic or an antagonistic effect, which obviously would
      need to be taken into account in determining combinations with new agents
      targeting angiogenesis.

PMID- 16101141
TI  - Expression profiles of apoptotic genes induced by curcumin in human breast cancer
      and mammary epithelial cell lines.
AB  - Curcumin (diferuloyl methane), the yellow-colored dietary pigment from the
      rhizomes of turmeric, has been recognized as a chemopreventive agent because of
      its antitumor, antioxidant and antiproliferative effects. The cytotoxic,
      apoptotic and gene regulatory effects of both turmeric and curcumin were
      investigated in the MCF-7 human breast cancer carcinoma cell line and compared
      with the effects in MCF-10A human mammary epithelial cells. MCF-7 cells were more
      sensitive to turmeric and curcumin than MCF-10A cells. MCF-10A cells retained
      comparatively less curcumin in the medium than MCF- 7 cells after 24 h, thereby
      reducing the cytotoxic effect. Curcumin induced a significantly higher percentage
      of apoptosis in MCF-7 than MCF-10A cells at all doses. Microarray hybridization
      of Clonetech apoptotic arrays with labeled first-strand probes of total RNA was
      performed to identify and characterize the genes regulated by curcumin in tumor
      cells. Of the 214 apoptosis-associated genes in the array, the expression of 104
      genes was altered by curcumin treatment. The gene expression was altered up to 14
      fold levels in MCF-7 as compared to only up to 1.5-fold in the MCF-10A cell line
      by curcumin. Curcumin up-regulated (>3 fold) 22 genes and down-regulated (<3
      fold) 17 genes at both 25 microg/ml and 50 microg/ml doses in the MCF-7 cell
      line. The up-regulated genes include HIAP1, CRAF1, TRAF6, CASP1, CASP2, CASP3,
      CASP4, HPRT, GADD45, MCL-1, NIP1, BCL2L2, TRAP3, GSTP1, DAXX, PIG11, UBC, PIG3,
      PCNA, CDC10, JNK1 and RBP2. The down-regulated genes were TRAIL, TNFR, AP13,
      IGFBP3, SARP3, PKB, IGFBP, CASP7, CASP9, TNFSF6, TRICK2A, CAS, TRAIL-R2, RATS1,
      hTRIP, TNFb and TNFRSF5. While a dose-dependent gene expression change was
      noticed in some genes, opposite regulatory effects were induced by different
      curcumin doses in three apoptotic genes. These results suggest that curcumin
      induces apoptosis in breast cancer cells by regulation of multiple signaling
      pathways, indicating its potential use for prevention and treatment of cancer.

PMID- 16101142
TI  - Binding of recombinant mistletoe lectin (aviscumine) to resected human
      adenocarcinoma of the lung.
AB  - BACKGROUND: Lectins, carbohydrate proteins, bind to glycoconjugates of all
      mammalian cells, including cancer cells. Aberrant glycosylation, detected by
      lectin histochemistry, can predict outcome in some tumour entities. One such
      lectin is aviscumine (recombinant mistletoe lectin). Aviscumine has cytotoxic
      effects and can therefore be used as anti-tumour therapy. MATERIALS AND METHODS:
      Lectin histochemistry with aviscumine was performed on primary tumour sections
      from resected adenocarcinoma of the lung. Staining results were then correlated
      with the clinical course of the patients. RESULTS: Most of the adenocarcinomas
      (92.5%) bound aviscumine. Kaplan-Meier analysis revealed no correlation between
      aviscumine binding and progression-free survival or overall survival. CONCLUSION:
      These results suggest that for the selected group of patients with adenocarcinoma
      of the lung aviscumine binding activity can not serve as a prognostic factor.
      More strikingly, however, aviscumine binds to malignant cells in 92.5% of the
      patients. This is an indicator for the use of aviscumine as a possible target for
      tumour therapy.

PMID- 16101143
TI  - Blockade of B7-H1 with sPD-1 improves immunity against murine hepatocarcinoma.
AB  - BACKGROUND: The B7-H1/PD-1 pathway has been demonstrated to be involved in tumor
      evasion. In a previous study, we constructed a eukaryotic expression plasmid (pPD
      1A), which expresses soluble PD-1 (sPD-1). In this study, the question of whether
      or not the blockade of B7-H1 with sPD-1 in vivo and vitro can improve antitumor
      immunity was investigated. MATERIALS AND METHODS: The proliferation of
      lymphocytes activated by dendritic cells (DCs), which were treated with sPD-1 in
      vitro, was detected with MTT colorimetry. Mice inoculated with H22 cells were
      treated by intramuscular injection with pPD-1A. The mRNA expression was analyzed
      with RT-PCR. RESULTS: The early activation of lymphocytes in vitro was partly
      improved by sPD-1 blockade. The growth of H22 cells was inhibited significantly
      after pPD-1A administration. The mRNA expression of 4-1BB, B7.1, IFN-gamma and
      TNF-alpha of lymphocytes was up-regulated and that of OX40 and IL-10 was down
      regulated after pPD-1A administration. CONCLUSION: Blockade of the PD-1/B7-H1
      pathway with sPD-1 may be a promising strategy for immunotherapy for
      hepatocarcinoma. Both cytokines and co-stimulatory molecules of lymphocytes could
      be regulated by sPD-1 blockade.

PMID- 16101144
TI  - Sensitisation of Ehrlich ascitic tumour cells to methotrexate by inhibiting
      glutaminase.
AB  - BACKGROUND: Glutaminase activity is correlated with cancer proliferation and with
      growth rate in normal cells. Ehrlich ascites tumour cells (EATC) and their
      derivative 0.28AS-2 cells, which express antisense glutaminase mRNA, show
      differences in both morphology and tumorigenic capacity. MATERIALS AND METHODS:
      Cell viability was determined with the microtetrazolium cytotoxicity test assay.
      Immunofluorescence staining with annexin-V and propidium iodide was carried out
      to assess the number of apoptotic cells. RESULTS: 0.28AS-2 cells are less
      resistant to H2O2 than EATC, since half the concentration of H2O2 caused a
      similar effect on the cell population in 24 h. Methotrexate significantly
      inhibited the proliferation of both EATC and 0.28AS-2 cells at concentrations
      higher than 64 nM after 48 h of exposure. CONCLUSION: 0.28AS-2 cells are highly
      sensitised to methotrexate. These results provide insights into the possible role
      of glutaminase in cancer therapy by demonstrating that the expression of
      antisense mRNA for glutaminase decreases chemoresistance to some pro-apoptotic
      agents.

PMID- 16101145
TI  - Proteasome inhibitors abolish cell death downstream of caspase activation during
      anti-microtubule drug-induced apoptosis in leukemia cells.
AB  - PURPOSE: Anti-microtubule drugs and proteasome inhibitors are currently among the
      most intensively studied anti-tumor agents, however little is known about their
      pharmacological interactions at the cellular level. MATERIALS AND METHODS: The
      human promyelocytic leukemia cell line, HL-60, was exposed to nocodazole or
      etoposide in combination with proteasome or caspase inhibitors. Apoptotic cell
      death was detected by flow cytometry as sub-G1 population. Caspase and proteasome
      activities were monitored by the fluorogenic substrates Ac-DEVD-AMC and Suc-LLVY
      AMC, respectively, in cell lysate. Heat shock protein 70 (HSP70) expression was
      determined by Western blotting. RESULTS: Nocodazole, a microtubule inhibitor,
      induced caspase-dependent apoptosis in the HL-60 cell line. At sub-cytotoxic
      concentrations, proteasome inhibitors, including MG-132 or clasto-beta-lactone,
      decreased nocodazole-induced apoptotic DNA fragmentation without affecting the
      induction of caspase-3 activity. In contrast, MG-132 decreased both DNA
      fragmentation and caspase activation induced by etoposide, a topoisomerase-II
      inhibitor. HSP70 had previously been found to inhibit apoptosis independently
      from caspase activation. In this study, MG-132 up-regulated HSP70 protein
      expression, both in the presence or absence of nocodazole. CONCLUSION: Proteasome
      inhibitors decreased anti-microtubule agent-induced apoptotic DNA fragmentation
      downstream of caspase-3 activation, possibly due to increased HSP70 expression.
      The results indicate that combination treatment with these novel anti-tumor
      agents in leukemia requires careful evaluation of their molecular interaction at
      the level of apoptosis induction.

PMID- 16101146
TI  - Progress in molecular mechanisms of tumor metastasis and angiogenesis.
AB  - The development of metastases is the major cause of death for cancer patients,
      however, the mechanisms of tumor invasion and acquisition of capability to
      metastasize remain unclear. During the past decade, knowledge regarding the
      molecular and cellular processes involved in the regulation of tumor metastases
      has dramatically increased and has been focussed on cross-talk between selected
      cancer cells and the specific organ microenvironment. The three-step development
      of the invasive phenotype of cancer cells is described: cell attachment, local
      proteolysis and cell migration. The molecular analysis of invasion-associated
      cellular activities, mainly the role of homotypic and heterotypic cell-cell
      adhesions, cell-matrix interactions, proteolysis mechanisms and migration
      properties of cancer cells, are also discussed. The role of tumor phenotype and
      microenvironment in the metastatic predilection for a specific organ site is
      pointed out, considering the recent reports which indicate that the capacity to
      metastasize might be acquired early during multistep tumorigenesis, thereby also
      predicting the site of metastasis. In addition, this review summarizes the
      current knowledge regarding angiogenesis regulation in progressive tumor growth
      and in the complex, multistep nature of tumor cell dissemination. A better
      understanding of the linkage between genetic and epigenetic events in metastases
      development may result in new anticancer treatment strategies.

PMID- 16101147
TI  - Suppression of renin-angiotensin system attenuates hepatocarcinogenesis via
      angiogenesis inhibition in rats.
AB  - Recent studies have shown that the renin-angiotensin system (RAS) as well as
      angiogenesis is involved in tumor development. The aim of the present study was
      to examine the interaction of RAS, angiogenesis and a potent angiogenic factor,
      namely the vascular endothelial growth factor (VEGF), in the hepatocarcinogenesis
      process. In a diethylnitrosamine-induced rat hepatocarcinogenesis model, a
      clinically used angiotensin-converting enzyme inhibitor, perindopril (PE),
      significantly suppressed glutathione S-transferase placental form (GST-P)
      positive preneoplastic lesions along with inhibition of neovascularization in the
      liver. The hepatic expression of VEGF was also attenuated. The degree of
      angiogenesis correlated well with the development of preneoplastic lesions. Our
      in vitro study showed that PE significantly suppressed VEGF-induced tubular
      formation and the migration of endothelial cells (EC), whereas it did not affect
      the proliferation of EC. These results suggested that RAS plays an important role
      in hepatocarcinogenesis, at least partly through VEGF-mediated angiogenesis.

PMID- 16101148
TI  - The diimide drug PIPER has a cytotoxic dose-dependent effect in vitro and
      inhibits telomere elongation in HELA cells.
AB  - It is known that, in vitro, PIPER (N,N'-bis [2-(1-piperidino)ethyl]-3,4,9,10
      tetracarboxylic diimide) induces the formation of the Hoogsteen quadruplex
      structure in telomere DNA, thus inhibiting the polymerisation of telomeric
      repeats. Since the action of PIPER in vivo has been scarcely investigated, this
      study was addressed to gain some insight into the effects of this drug on
      cultured HeLa cells. Vital staining with erythrosine, performed on cells exposed
      to different PIPER concentrations (from 1 to 50 microM), showed that the drug
      exerts a dose-dependent cytotoxic effect, clearly evident after a short-term (24
      h) treatment. This early cytotoxic effect of PIPER on cultured HeLa cells was
      confirmed by a spectrophotometric/colorimetric method employing
      methylthiazoletetrazolium (Mossmann assay). Hematoxylin/eosin staining of cells
      treated with PIPER for 24 h showed a nuclear condensation and a cytoplasmic
      vacuolisation, very pronounced at higher drug concentrations. These pictures
      suggest that PIPER-induced cell death might be of the apoptotic type. Finally,
      the anti-telomerase activity of PIPER was monitored by TRAP assay, performed on
      HeLa cell nuclear extracts treated with increasing drug concentrations. It was
      found that some inhibition of telomerase is apparent even at low concentrations,
      while at the highest concentration the enzyme is completely inhibited. These
      results indicate that the cytotoxic power of PIPER is possibly related to its
      antitelomeric effect.

PMID- 16101149
TI  - Activation of p38 mitogen-activated protein kinase is necessary for gemcitabine
      induced cytotoxicity in human pancreatic cancer cells.
AB  - BACKGROUND: Gemcitabine is a pyrimidine nucleoside analog that is clinically
      active against pancreatic cancer. We have recently demonstrated that p38 MAPK is
      specifically activated by gemcitabine and that pharmacological blockade of p38
      MAPK signaling prevented gemcitabine-induced apoptosis in human pancreatic cancer
      cells. In this study, we further investigated the implication of p38 MAPK in the
      cytotoxic action of gemcitabine. MATERIALS AND METHODS: Cells expressing a
      dominant-negative mutant of p38 MAPK were generated. Clonogenic assays were used
      to assess the long-term effect on cancer cell viability in the human pancreatic
      cancer cells, PK1 and PCI43. The p38 MAPK activation level was assessed using an
      antibody specific to the phosphorylated form. RESULTS: Gemcitabine increased the
      activation level of p38 MAPK in a dose-dependent manner and induced apoptosis in
      the two tested human pancreatic cancer cell lines. The selective p38 MAPK
      inhibitors, SB203580 and SB202190, reduced gemcitabine-induced activation of p38
      MAPK, prevented the gemcitabine-induced apoptosis and increased long-term
      clonogenic survival. Overexpression of a dominant-negative p38 mutant in cells
      resulted in the reduction of gemcitabine-induced p38 MAPK activation and
      apoptosis, and increases in clonogenic survival. CONCLUSION: These results
      strongly suggest that the activation of p38 MAPK signaling is necessary for
      gemcitabine-induced cell death in human pancreatic cancer cells. Based upon these
      results, we suggest that molecules of p38 MAPK signaling pathways should be
      listed as novel targets for gemcitabine-based therapy.

PMID- 16101150
TI  - 12-O-retinoylphorbol-13-acetate (RPA) behaves like a retinoid-derivative in
      binding to retinol-binding-protein: a correlation with its specific action as an
      incomplete tumor promoter?
AB  - 12-O-retinoylphorbol-13-acetate (RPA), an incomplete tumor promoter of the
      phorbol ester type and protein kinase C (PKC) activator, consists of two
      characteristic structural elements: the phorbol body and the retinoyl ester
      chain. Therefore, possible binding of the incomplete tumor promoter RPA to the
      human transport protein retinol-binding-protein (RBP) has been examined by
      molecular modeling methods and experimental binding studies. The calculated
      prediction of binding properties was primarily based on a comparative geometrical
      approach. It was shown that the beta-ionone-ring of RPA was not altered within
      the binding pocket of RBP (molecular modeling) compared to retinoic acid (X-ray
      crystallographic data). The torsion angle C5'-C6'-C7'-C8', determining the
      conformation of the RBP-beta-ionone-ring relative to the isoprene tail, is
      rotated by 42 degrees for RPA compared to retinol and to retinoic acid,
      respectively. Combining all the results from force field calculations, MD
      simulations and geometrical comparisons, the conclusion could be drawn that RPA
      should be able to bind to RBP. This interaction should be less strong than that
      with its natural ligand retinol or with retinoic acid. This prediction was proven
      experimentally. RPA was able to compete with retinoic acid for binding at RBP in
      human plasma. The binding properties were investigated using 3H-labeled retinoic
      acid in homologous and heterologous competition studies in a one-dimensional
      native polyacrylamide gel electrophoresis system. An approximately 2000-fold
      weaker binding of RPA to RBP as compared to retinoic acid was determined
      experimentally, confirming the prediction of the molecular modeling approach. The
      characteristic behaviour of RPA as an incomplete promoter, due to possible
      binding to PKC and RBP, is discussed.

PMID- 16101151
TI  - Kinetics of radical-scavenging activity of hesperetin and hesperidin and their
      inhibitory activity on COX-2 expression.
AB  - The radical-scavenging activities of the flavanones hesperetin and hesperidin
      were investigated by differential scanning calorimetry (DSC) monitoring of the
      polymerization of methyl methacrylate initiated by 2,2'-azobisisobutyronitrile
      (AIBN, an R* radical) or benzoylperoxide (BPO, a PhCOO* radical) at 70 degrees C
      under nearly anaerobic conditions. Their stoichiometric factor (number of free
      radicals trapped by one mole of antioxidant moiety (n)) and the ratio of the rate
      constant of inhibition to that of propagation (k(inh)/k(p)) were determined and
      compared with that for trolox The n value declined in the order trolox (2.0) >
      hesperetin (0.8) > hesperidin (0.2) in the AIBN system, whereas it declined in
      the order hesperetin (0.9) > trolox (0.1) > hesperidin (0.0) in the BPO system.
      The k(inh)/k(p) value declined in the order hesperidin (195) > hesperetin (33) >
      trolox (12) in the AIBN system, whereas it declined in the order hesperidin (362)
      > trolox (127) > hesperetin (18) in the BPO system. The n value of about 1 for
      hesperetin with a relatively small k(inh)/k(p) value suggests the formation of
      dimers, as a result of the coupling reaction of phenolic monomers. In contrast, n
      values << 1 for hesperidin and trolox in the BPO system resulted in very high
      values for k(inh)/k(p). Hesperidin was also much more able to suppress the growth
      of methyl methacrylate radicals, although its n value was small, suggesting that
      this compound may also suppress polyunsaturated fatty acid radicals. In the
      concentration range 250-500 microM, hesperetin and hesperidin showed potent
      inhibition of LPS-induced expression of the COX-2 gene in RAW 264.7 cells,
      suggesting the anti-inflammatory activity of these compounds. The ability of
      hesperetin and hesperidin to suppress COX-2 gene expression may be a consequence
      of their antioxidant activity.

PMID- 16101152
TI  - Isothiocyanates induce cell cycle arrest, apoptosis and mitochondrial potential
      depolarization in HL-60 and multidrug-resistant cell lines.
AB  - Isothiocyanates from cruciferous vegetables have been identified as potent
      anticancer agents in animal and human epidemiological studies. The present study
      compared the biological activities of six dietary isothiocyanates (ITCs), allyl
      ITC (AITC), benzyl-ITC (BITC), phenethyl-ITC (PEITC), sulforaphane (SFN), erucin
      (ERN) and iberin (IBN), on cell cycle progression, apoptosis induction and
      mitochondrial transmembrane potential in multidrug-resistant HL60/ADR (MRP-1
      positive) and HL60/VCR (Pgp-1-positive) cells in comparison to the parent cell
      line HL60. Multidrug-resistant HL60/ADR and HL60/VCR cells were less sensitive
      than the parental HL60 cells to all the six tested ITCs, since the medians of
      IC50 values were 2.8- and 2.0-fold higher. All the selected ITCs induced time-
      and dose-dependant G2/M arrest, with the most effective AITC (10 microM, 24 h)
      inducing 52% G2/M accumulation in HL60 cells. Apoptosis was determined by Annexin
      V-FITC staining, metabolic conversion of fluorescein diacetate and sub-G1
      population quantification. Cell cycle distribution and mitochondrial JC-1
      aggregation were determined by flow cytometry. The effectiveness of ITCs in
      apoptosis induction and mitochondrial potential dissipation followed the order:
      BITC=PEITC>ERN=IBN>AITC>SFN.

PMID- 16101153
TI  - Quantitative estimation of matrix metalloproteinases 2 and 7 (MMP-2, MMP-7) and
      tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1, TIMP-2) in
      colorectal carcinoma tissue samples.
AB  - BACKGROUND: An essential step in the process of tumor invasion and metastasis
      involves the degradation of tissue barriers in the extracellular matrix (ECM),
      particularly in the basal membrane (BM). Matrix metalloproteinases (MMPs) and
      tissue inhibitors of matrix metalloproteinases (TIMPs), in particular MMP-2, MMP
      7, TIMP-1 and TIMP-2, play an important role in the process of ECM and BM
      degradation in connection with tumor invasion. The aim of our study was to assess
      the levels of MMP-2, MMP-7, TIMP-1 and TIMP-2 mRNA expression in colorectal
      carcinoma tissue samples and to correlate them with the stage of the disease.
      PATIENTS AND METHODS: The study included samples of tumor tissue of 38 patients
      with colorectal carcinoma and samples of tissue of 11 patients with benign
      disease. The expression levels of mRNA MMP-2, MMP-7, TIMP-1, TIMP-2 and
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as housekeeping gene, were
      quantified in tissue samples using the method of reverse transcription real-time
      PCR. RESULTS: The levels of mRNA expression of MMP-2, MMP-7 and TIMP-1 were
      significantly higher in tumor tissue samples that in the control tissue
      (p<0.0005, p<0.0007 and p<0.0004). In addition the presence of mRNA MMP-2, MMP-7,
      TIMP-1 and TIMP-2 in tumor tissue samples in these parameters was significantly
      higher than in the control tissue (p<0.003, p<0.0001, p<0.0001 and p<0.05).
      CONCLUSION: This pilot study demonstrated that a significant difference in the
      level and in the presence of mRNA MMP-2, MMP-7 and TIMP-1 expressions between
      tumor colorectal and control colorectal tissues might be helpful for the
      prognosis of colorectal cancer.

PMID- 16101154
TI  - Biochemical changes of mevalonate pathway in human colorectal cancer.
AB  - BACKGROUND: Alterations in the mevalonate pathway may contribute to malignant
      cell growth. There are differences in the aetiology, clinical behaviour,
      pathological and genetic features in cancer of the right versus the left colon.
      Here, 3-hydroxy-3-methylglutatyl coenzyme A (HMG-CoA) reductase,
      farnesylpyrophosphate (FPP) synthase and farnesyltransferase (Ftase) activities
      were measured in human colorectal cancer (CRC) and normal mucosa in order to
      evaluate their role as potential markers of malignancy, also in relation to
      cancer location. PATIENTS AND METHODS: HMG-CoA reductase, FPP synthase and Ftase
      activities were determined in CRC and normal mucosa of 90 patients by
      radiochemical assay. RESULTS: The enzymatic activities were higher in cancer than
      in normal mucosa. The tumours located at the left side showed higher HMG-CoA
      reductase activity, whereas the right side tumours showed higher levels of Ftase
      and FPP synthase activity. CONCLUSION: The determination of mevalonate pathway
      enzymes in relation to CRC location may be clinically relevant in designing
      anticancer targeted therapies.

PMID- 16101155
TI  - Evaluation of anti-vascular therapy with texture analysis.
AB  - BACKGROUND: Texture analysis can be used to identify and discriminate between
      objects in an image and has already been used for the characterization of
      diseases. The present study evaluated the potential of texture analysis for
      monitoring tumor cell viability during treatment with an anti-vascular drug.
      MATERIALS AND METHODS: Texture analysis of T2-weighted magnetic resonance images
      of C3H mammary carcinomas in mice was used to study tumor cell viability during
      treatment with the anti-vascular drug combretastatin A-4 disodium phosphate
      (CA4DP). Texture analysis was done by MaZda, and boot strap statistics were used
      to analyze the results. RESULTS: The results revealed significant differences in
      the textures of T2-weighted images when non-tumor tissue and tumor tissue were
      compared. Furthermore, selected texture parameters were significantly different
      when image data from before and after CA4DP administration were analyzed.
      CONCLUSION: Texture analysis is helpful in the diagnosis of different types of
      tissues, especially when these tissues can not be recognized by human observers.
      Some functional changes, such as perfusion changes in the tumor, can also be
      detected by texture analysis.

PMID- 16101156
TI  - Effects of heavy water (D2O) on human pancreatic tumor cells.
AB  - BACKGROUND: Pancreatic cancer constitutes an entity which is difficult to treat
      and, therefore, mostly fatal. Since heavy water (deuterium oxide, D2O) was shown
      to be active in various cancer cell lines in vitro and in vivo, we now
      investigated its effects in human pancreatic tumor cells. MATERIALS AND METHODS:
      The cytotoxic effects of D2O were examined in three pancreatic cancer cell lines
      (AsPC-1, BxPC-3 and PANC-1). Induction of apoptosis was determined by
      Hoechst/propidium iodide double staining and cell cycle distribution was
      investigated by FACS analysis. RESULTS: Employing a clonogenic assay, D2O yielded
      IC50 values of 15%, 18% and 27% in AsPC-1, PANC-1 and BxPC-3 cells, respectively,
      and led to the induction of apoptosis when compared to untreated controls.
      Moreover, D2O caused a cell cycle arrest in the G2-M-phase (BxPC-3, PANC-1) or in
      the S-phase (AsPC-1). CONCLUSION: It is hoped that D2O might offer an additional
      option for the treatment of pancreatic carcinomas.

PMID- 16101157
TI  - Hyperoxia-induced improvement of the in vitro response to gemcitabine in
      transitional cell carcinoma.
AB  - BACKGROUND: Anemic tissue hypoxia can decrease the effects of chemotherapy in
      bladder cancer. Hypoxia leads to overexpression of hypoxia-inducible factor (HIF)
      and increased synthesis of epidermal growth factor (EGF) and vascular endothelial
      growth factor (VEGF). Tumor cell survival, invasion and angiogenesis thereby
      compromise treatment. MATERIALS AND METHODS: Monolayer cultures of RT112, RT4,
      T24 and TCC SUP cells were incubated with or without gemcitabine and different
      gas mixtures (hypoxia, normoxia or hyperoxia). Cell proliferation (microculture
      tetrazolium assay), VEGF (enzyme-linked immunosorbent assay) and HIF-1alpha
      (Western blot analysis) were determined. RESULTS: Hypoxia led to increased
      proliferation of transitional cell carcinoma (TCC) cells and elevated levels of
      HIF-1alpha and VEGF. Hyperoxia inhibited cell growth and lowered the
      concentration of VEGF. Treatment with gemcitabine was less effective under
      hypoxia. CONCLUSION: Hypoxia enhances TCC growth and may intensify angiogenesis
      mediated by VEGF. Hypoxia compromises treatment with gemcitabine. Correction of
      anemia might provide advantages in chemotherapeutic strategies for TCC.

PMID- 16101158
TI  - Expression of p8 protein in medullary thyroid carcinoma.
AB  - BACKGROUND: The p8 protein is involved in various cells under cellular stress,
      such as apoptotic stimuli. In this study, p8 protein expression was investigated
      in human medullary thyroid carcinoma. in order to elucidate its physiological
      significance. MATERIALS AND METHODS: We immunohistochemically investigated p8
      expression in 69 cases of medullary thyroid carcinoma. RESULTS: Thirty cases
      (43.4%) were regarded as a high group of p8 expression with a labelling index of
      50% or higher. The p8 expression level was directly linked to lymph node
      metastasis, extrathyroid extension and UICC stage. Furthermore, there were no
      cases showing low p8 expression, but 24.8% of those with high p8 expression
      showed recurrence. However, p8 expression was not linked to the apoptotic index.
      CONCLUSION: These findings suggest that p8 expression plays an important role in
      the progression of medullary carcinoma, but does not have an anti-apoptotic
      function.

PMID- 16101159
TI  - The combined treatment of 1,25-dihydroxyvitamin D3 and a non-steroid anti
      inflammatory drug is highly effective in suppressing prostate cancer cell line
      (LNCaP) growth.
AB  - BACKGROUND: The active metabolite of vitamin D3, 1,25(OH)2D3, is known to possess
      anti-proliferative and pro-differentiative activities in prostate cancer (PCa)
      cells. However, its clinical use is limited because of the risk of hypercalcemia.
      Concurrent administration of lower doses of 1,25(OH)2D3 together with other
      anticancer drugs may help to overcome this obstacle and lead to an effective and
      tolerable therapy. In the present in vitro study, we investigated the combined
      anti-cancer effect of 1,25(OH)2D3 and ibuprofen, a well-known non-steroidal anti
      inflammatory drug (NSAID) that is also recognized for its ability to reduce
      prostate cancer development. MATERIALS AND METHODS: An androgen-sensitive
      prostate cancer cell line (LNCaP), grown in medium containing androgen (5alpha
      dihydrotestosterone (DHT)) or without it, was treated with 1,25(OH)2D3 or
      ibuprofen alone or with a combination of both drugs. The effects of the
      treatments on LNCaP cell proliferation, cell cycle and apoptosis were evaluated
      by the thymidine incorporation method, the propidium iodide method and ELISA,
      respectively. The unpaired t-test was used for statistical analysis. RESULTS:
      Simultaneous treatment of LNCaP cells grown without DHT with 10 nM 1,25(OH)2D3
      and 0.2 mM ibuprofen decreased cell growth by 42% (p<0.001, compared to the
      control cells). This effect was found to be additive since each single drug
      reduced cell proliferation by only 24%. On the other hand, highly significant
      synergistic cell growth inhibition (67%, p<0.001) was achieved by combined
      treatment of 1,25(OH)2D3 and ibuprofen in DHT-stimulated LNCaP cells. This
      combined treatment was also found to be effective in decreasing the cell
      transition from G1- to S-phase (p<0.003) and effective in enhancing apoptosis.
      CONCLUSION: Although both 1,25(OH)2D3 and ibuprofen demonstrate in vitro anti
      carcinogenic activities as a single drug treatment, the present results showed
      that the combined use of 1,25(OH)2D3 with ibuprofen is superior to treatment with
      a single drug.

PMID- 16101160
TI  - Glucose transporter GLUT1 in colorectal adenocarcinoma cell lines is inversely
      correlated with tumour cell proliferation.
AB  - The high glucose consumption of tumour cells has been well known since Warburg's
      investigations. Nevertheless, the reason for this phenomenon is still a matter of
      speculation. Glucose uptake of tumour cells is mainly mediated by GLUT1. In this
      study, the question of whether glucose uptake as well as expression of GLUT1 are
      both related to tumour cell proliferation was addressed. Three kinetically
      different cell lines of colorectal adenocarcinomas (HRT-18, HT29 and CX-2) were
      used for the experiments. All the cell lines expressed GLUT1 at a high level,
      being mainly localized within the cell membrane and the endoplasmic reticulum.
      Surprisingly, the highest expression of GLUT1 was found in the most slowly
      proliferating cell line, CX-2. Moreover, induction of cell cycle arrest increased
      both GLUT1 expression and glucose consumption, as well as global protein
      synthesis. These data suggest that the protein synthesis of tumour cells is much
      more glucose-consuming than proliferation and that both processes are inversely
      related.

PMID- 16101161
TI  - Y-box-binding protein-1 expression is not correlated with p53 expression but with
      proliferating cell nuclear antigen expression in non-small cell lung cancer.
AB  - Transcription factor Y-box-binding protein 1 (YB-1), which binds to the inverted
      CCAAT box, is not only involved in the transcription of various genes, but also
      in cell proliferation and DNA repair. The aim of this study was to detect YB-1
      and p53 expression and their relationship to proliferating cell nuclear antigen
      (PCNA) in non-small cell lung cancer (NSCLC) using immunohistochemical (IHC)
      staining, and to evaluate the relationship between their expression levels and
      the prognosis of patients with NSCLC. Positive expressions of YB-1, p53 and PCNA
      were detected in NSCLC cells in 43 (45.7%), 33 (35.0%) and 45 (47.9%) out of 94
      patients, respectively. No significant differences were observed between YB-1
      expression and the patients' gender, age at surgery, pathological stage,
      pathological T status, pathological N status, or pathological M status. The mean
      PCNA-labelling index (LI) for cells was 40.7+/-2.6. Also, a significant
      correlation between YB-1 and PCNA-LI was found (p<0.01), but none was found
      between p53 expression and PCNA. The positive expression of YB-1 was associated
      with squamous cell carcinoma and large cell carcinoma, compared with
      adenocarcinomas (p<0.01), and higher levels of PCNA-LI were associated with large
      cell carcinoma compared with adenocarcinomas and squamous cell carcinoma
      (p<0.01). These results suggest that YB-1 expression is correlated with PCNA
      expression in NSCLC. In addition, the DNA repair pathway and tumor proliferation
      mediated by YB-1 linking to PCNA may be responsible for controlling the growth of
      NSCLC.

PMID- 16101162
TI  - Evaluation of a dysfunctional and short-lived subset of monocyte-derived
      dendritic cells from cancer patients.
AB  - Monocyte-derived dendritic cells (Mo-DCs) were generated from peripheral blood
      monocytes of 12 healthy volunteers (hMo-DCs) and 11 patients (pMo-DCs) with
      malignancies by culture for 7 days with granulocyte-macrophage colony-stimulating
      factor and interleukin-4. In this study, we focused on the cytogram pattern by
      FACS analysis. A gate (R1) was set up by which more than 95% of hMo-DCs were
      contained. Mo-DCs having lower side scatter than the R1 (R2) comprised 4.5% of
      hMo-DCs and 24.2% of pMo-DCs. Expressions of antigen presentation-related
      molecules and phagocytic ability in the R2 of pMo-DCs were lower than those in
      the R1 population. The R2, but not R1, in pMo-DCs decreased in number between
      days 7 and 14, and expression levels of antigen presentation-related molecules in
      the living pMo-DCs on day 14 increased. The 11 patients received dendritic cell
      vaccine therapy with autologous, tumor-pulsed mature Mo-DCs (day 7). The low R2
      group (R2 < or = 10%, 3 patients) had a significantly higher positive delayed
      type hypersensitivity reaction against autologous tumor-pulsed Mo-DCs than that
      of the high R2 group (R2 > 10%, 8 patients) (p<0.001). These results indicate
      that the R2 of pMo-DCs may be a dysfunctional and short-lived subset.

PMID- 16101163
TI  - Individualized adjuvant chemotherapy guided by chemosensitivity test sequential
      to extended surgery for advanced gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Various adjuvant chemotherapy regimens have been
      proposed for patients with advanced gastric cancer; however, the majority of
      these trials failed to show a clear survival benefit over surgery alone. In this
      study, the feasibility and efficacy of a strategy of extended surgery combined
      with individualized adjuvant chemotherapy for advanced gastric cancer with
      serosal invasion and nodal involvement was examined. PATIENTS AND METHODS: Sixty
      four patients with advanced gastric cancer underwent gastrectomy with extended
      lymph node dissection. After surgery, a chemosensitivity test by MTT assay, using
      highly purified tumor cells, was performed, and the patients received
      individualized adjuvant chemotherapy on the basis of the results of this
      chemosensitivity test. RESULTS: Overall survival in the chemosensitivity-guided
      chemotherapy (CSC) group was significantly better than the standard chemotherapy
      (SC) and the no-chemotherapy (NC) group (p<0.05). In patients with stage IV
      disease, the 5-year survival rate was 38.1% in the CSC group and 0% in the SC +
      NC group, respectively, with a significant difference being observed in the two
      survival curves (p<0.01). In patients with paraaortic node involvement, survival
      in the CSC group was significantly better than that in the SC + NC group
      (p<0.01). On the other hand, in patients without paraaortic node involvement, no
      survival difference was observed between the two groups. CONCLUSION: The strategy
      of extended surgery combined with individualized adjuvant chemotherapy offers a
      favorable survival outcome for advanced gastric cancer patients with serosal
      invasion and nodal involvement.

PMID- 16101164
TI  - Classification of recurrent esophageal cancer after radical esophagectomy with
      two- or three-field lymphadenectomy.
AB  - BACKGROUND: Although patients with recurrent diseases have a very poor prognosis,
      appropriate pretreatment classification for management of recurrent esophageal
      cancers has yet to be identified. The patterns of recurrence following radial
      esophagectomy were retrospectively assessed, and evaluated for possible
      adaptation as a novel classification of recurrent esophageal cancer. PATIENTS AND
      METHODS: One hundred and sixty thoracic esophageal cancer patients (142 men; 18
      women), who underwent radical esophagectomy without preoperative treatment, were
      studied. RESULTS: Recurrence occurred in 59 (36.8%) patients. The relationship
      between recurrence and clinicopathological features revealed significant
      associations between recurrence and age at surgery (p<0.05), tumor (p<0.0001),
      lymph node (p<0.0001) and metastatic status (p<0.01), pathological stage
      (p<0.0001) and lymph node dissection (p<0.0001). Locoregional recurrence occurred
      in 13 (22%) patients, distant in 30 (51%) and mixed in 16 (27%). Mixed recurrence
      occurred the fastest and showed the poorest prognosis. A novel classification for
      recurrent esophageal cancer was proposed based on the clinical findings.
      Univariate analysis of the prognostic factors for post-recurrent survival
      revealed a significant association with distant organ recurrence (p<0.05).
      CONCLUSION: Mixed recurrence had a poorer outcome than other recurrences. The
      proposed classification of clinical findings for recurrent esophageal cancer was
      shown to be useful; however, further studies with a larger number of recurrent
      esophageal cancers are required for stage grouping of the proposed
      classification.

PMID- 16101165
TI  - Comparing PAP smear cytology, aided visual inspection, screening colposcopy,
      cervicography and HPV testing as optional screening tools in Latin America. Study
      design and baseline data of the LAMS study.
AB  - OBJECTIVES: This is a European Commission (EC)-funded ongoing study known as the
      LAMS (Latin American Screening) study, where PAP smear/liquid-based cytology and
      screening colposcopy were compared with i) three optional screening tools [visual
      inspection with acetic acid (VIA), or Lugol's iodine (VILI), cervicography] and
      with ii) Hybrid Capture II from a) conventional samples and from b) self-samples,
      in women at different risk for cervical cancer in Brazil and Argentina. STUDY
      DESIGN: During 2002-2003, a cohort of 12,107 women attending four clinics:
      Campinas (CA), Sao Paulo (SP), Porto Alegre (PA) and Buenos Aires (BA), were
      interviewed for risk factors, and examined using the 8 diagnostic arms.
      Colposcopy was performed for women positive in any test and for 5% of women with
      baseline PAP-negative and 20% of HCII-negatives. All high-grade lesions (CIN2/3)
      were treated, and low-grade CIN are prospectively followed-up. RESULTS: Of the
      12,107 women, the following baseline data are available: epidemiological data
      (n=11,996), conventional PAP smears (n=10,363), LBC, SurePATH (n=320), LBC, DNA
      Citoliq (n=1,346), VIA (n=12.067), VILI (n=3,061), cervicography (n=279),
      screening colposcopy (n=3,437), HCII conventional (n=4,710), HCII self-sampling
      (n=246) and cervical biopsies (n=1,524). The four sub-cohorts differ
      significantly in all their baseline data on the implicated risk factors of
      cervical cancer, consonant with their origin from regions with different cancer
      incidence. Around 95% of all PAP smears were negative, with slight variations in
      the prevalence of LSIL and HSIL between the four centers. Significant differences
      were found in the detection rates of abnormal findings in VIA, VILI and
      colposcopy between the four centers (p=0.0001). The prevalence of HPV was
      practically identical (16.5-18.8%) in all four cohorts (p=0.486), with no
      differences in the relative viral loads. Biopsy results were different depending
      on whether the women underwent screening colposcopy (BA) or elective colposcopy
      (others). CONCLUSION: Four cohorts with significantly different baseline data are
      available, and prospective follow-up of these women permits analysis of whether
      variations in cervical cancer incidence in these regions is due to i) different
      natural history of the precursor lesions, or ii) due to different levels of
      exposure to the known risk factors.

PMID- 16101166
TI  - Successful pregnancy and normal delivery after whole craniospinal irradiation in
      two patients.
AB  - BACKGROUND: Two cases of normal pregnancies and deliveries after whole
      craniospinal irradiation (WCSI) are described, and whether the ovaries can be
      left out of the WCSI field by identifying ovarian position using magnetic
      resonance imaging (MRI) is determined. MATERIALS AND METHODS: The distance
      between the upper edge of the pubic symphysis and the central part of the ovary
      was measured on MRI in 17 women. RESULTS: The right ovary was located 20.3-68.4
      mm to the right of and 33.7-113.5 mm above the upper edge of the pubic symphysis;
      the left ovary was located 26.2-72.5 mm to the left and 25.8-106.6 mm above this
      edge. The lower border of the spinal field in WCSI should be the caudal border of
      the thecal sac, i.e., S2-S4. The line of this location, which nearly approximates
      normal ovarian position, should be employed in radiotherapy planning to avoid
      irradiating at least one ovary with its thecal sac. Omitting this area from the
      WCSI field in women of childbearing age with a good long-term prognosis,
      preserves potential fertility. CONCLUSION: It appears that the ovaries might be
      excluded from the WCSI field, using appropriate techniques, so as to preserve
      female fertility.

PMID- 16101167
TI  - Bi-weekly administration of docetaxel and gemcitabine as first-line therapy for
      non-small cell lung cancer: a phase II study.
AB  - BACKGROUND: The standard treatment for advanced non-small cell lung cancer
      (NSCLC) currently consists of platinum-based, combination chemotherapy of limited
      efficacy and possible toxicity. The bi-weekly administration of docetaxel and
      gemcitabine for advanced NSCLC was evaluated in a phase II study (objective
      response rate, median survival, median duration of response and safety). PATIENTS
      AND METHODS: A total of 170 cycles were administered to 31 patients with advanced
      NSCLC and a median age of 66 years (range 47-75 years). Patients received
      docetaxel 80 mg/m2 and gemcitabine 1000 mg/m2 on days 1 and 14 of a 28-day cycle.
      RESULTS: Sixteen patients achieved a PR (16/31, 55.2%), 3 patients had SD (3/31,
      10.3%) and 10 (10/31, 34.5%) had PD. The median time to disease progression was 3
      months (range 0-12 months) with a mean survival of 10 months (range 3-31 months).
      Haematological and non-haematological toxic effects were generally mild to
      moderate and manageable: Grade 3 neurotoxicity and allergy occurred in 2 patients
      (6.4%) and 1 patient (3.2%), respectively. Peripheral neuropathy, mostly grades 1
      and 2, was reported in 24 patients (77.4%). CONCLUSION: The bi-weekly
      administration of a docetaxel/gemcitabine combination with G-CSF support
      constitutes a tolerable and convenient regimen for the treatment of advanced
      NSCLC, with efficacy similar to that reported in other regimens.

PMID- 16101168
TI  - Evaluation of epoetin supplemented with oral iron in patients with solid
      malignancies and chronic anemia not receiving anticancer treatment.
AB  - OBJECTIVE: To evaluate the effectiveness and improvement in quality of life (QOL)
      of epoetin alfa administration supplemented with oral iron as a therapeutic
      regimen for patients with solid malignancies and anemia of chronic disease (ACD),
      not receiving chemotherapy and/or radiotherapy. PATIENTS AND METHODS: A total of
      100 patients with cancer-related anemia, not subjected to chemotherapy and/or
      radiotherapy, were randomized to receive for a maximum of 24 weeks either oral
      iron, equivalent to 200 mg elemental iron once daily, or epoetin alfa 40,000 IU
      subcutaneously once weekly plus oral iron once daily. RESULTS: Patients in the
      epoetin alfa group had, from baseline to study end, a mean increase in hemoglobin
      (Hb) levels of 2.4 g/dL, whereas in the control group the mean Hb level decreased
      by 0.1 g/dL, (p<0.001). Improvement in QOL as assessed by the LASA and the FACT
      An questionnaire were greater in patients in the epoetin alfa group than in the
      control group (mean change, LASA-energy level: 30.4 mm vs. 0.4 mm, -daily
      activities: 31.7 mm vs. 0.4 mm, -overall well-being. 32.4 mm vs. 4.9, FACT-An:
      43.3 vs. 13.4, respectively). As for ECOG score, patients in the epoetin alfa
      group had a mean improvement of 0.16 from baseline to study end (control group:
      0.06). Improvement in QOL parameters and in ECOG scores correlated positively
      with increased hemoglobin levels. CONCLUSION: Our results suggest that weekly
      epoetin alfa therapy supplemented with daily oral iron increases Hb levels and
      improves QOL in patients with solid malignancies and ACD who are not receiving
      chemotherapy and/or radiotherapy. This regimen offers optimal therapy in this
      population taking into consideration physician's convenience and patient's
      compliance.

PMID- 16101169
TI  - Activity of chemotherapy in mucinous epithelial ovarian cancer: a retrospective
      study.
AB  - OBJECTIVE: Mucinous ovarian carcinoma has a poorer prognosis compared with other
      histological subtypes. The aim of this study was to evaluate, retrospectively,
      the activity of first-line and second-line chemotherapy in patients with mucinous
      ovarian cancer in a mono-institutional series. PATIENTS AND METHODS: In the
      period under survey (1996-2003), 225 new patients with ovarian cancer were
      treated. Twenty-one out of these patients (9.3%) received a diagnosis of mucinous
      ovarian cancer. The median age, performance status, stage at diagnosis and
      residual disease after surgery were similar in the mucinous compared to the other
      histological groups (P=NS). RESULTS: In mucinous ovarian cancer the grading of
      the tumors was 2 in 76% of the cases, while grade 3 was more frequent in the
      other subtypes (p<0.002). Eighty-five % of the patients had received
      carboplatin/paclitaxel, while the remaining cases had been treated with a
      cisplatin-based chemotherapy not containing paclitaxel. Two patients with early
      stage were treated with adjuvant chemotherapy and were not evaluable for response
      while 19 patients had measurable disease (12 pts) or were assessed at second-look
      (7 pts). Forty-seven % of the 19 patients experienced disease progression during
      first-line, while 31.5% and 10.5% complete and partial responses were recorded,
      respectively. Fifteen out of the 21 patients had progressed at the time of the
      analyses. Sixty % of the progressed patients were platinum-refractory, 3 cases
      were platinum-sensitive and 3 platinum-resistant. The 3 platinum-sensitive
      patients were treated with single agent carboplatin without any response. No
      response was recorded with topotecan or liposomal doxorubicin when given as
      second- or third-line treatment in platinum-refractory/resistant patients.
      CONCLUSION: Mucinous ovarian cancer has a poor response to chemotherapy both in
      the first-line and in the recurrence settings. Studies with alternative
      chemotherapy combinations are mandatory in this histological subgroup.

PMID- 16101170
TI  - Radical external beam radiotherapy for clinically localized prostate cancer in
      Japan: changing trends in the patterns of care process survey between 1996-1998
      and 1999-2001.
AB  - BACKGROUND: This report presents results of a study delineating changing trends
      in radical external beam radiotherapy usage for prostate cancer between the 1996
      1998 and 1999-2001 Patterns of Care Study (PCS) survey periods in Japan.
      MATERIALS AND METHODS: Out of the 694 patients comprising the 1996-1998 and 1999
      2001 PCS surveys, the current study analyzed data for 444 patients with
      clinically localized prostate cancer treated with external beam radiotherapy
      (1996-1998 PCS: 161 patients; 1999-2001 PCS: 283 patients). RESULTS:
      Significantly higher percentages of patients had earlier T stages (T1-T2: 48.2%)
      and well-differentiated tumors (23.6%) between 1999 and 2001 than between 1996
      and 1998 (T1-T2: 34.6%, well-differentiated tumors: 15.1%). Although only 5.9% of
      patients were treated with radiotherapy by their own choice during 1996-1998, a
      larger proportion (26.5%) chose this treatment during 1999-2001. The median
      radiation dose was 65.0 Gy during 1996-1998, increasing to 68.4 Gy during 1999
      2001. Moreover, the incidence of total treatment doses of > or = 70 Gy was higher
      during 1999-2001 (38.0%) than during 1996-1998 (17.5%). On the other hand, the
      percentage of patients receiving conformal therapy during 1996-1998 (49.1%) was
      almost the same as during 1999-2001 (50.2%). The median numbers of full-time
      equivalent (FTE) radiation oncologists increased in academic institutions (1.8 in
      1996-1998; 2.4 in 1999-2001), while those in non-academic institutions remained
      low (0.5 in 1996-1998; 0.45 in 1999-2001). CONCLUSION: In Japan, fewer prostate
      cancer patients treated with radical external beam radiotherapy had advanced
      diseases. Increasing percentages of patients chose radiotherapy and received
      increased radiation doses, which might reflect the growing acceptance of radical
      external beam radiotherapy as a first-line treatment for prostate cancer in
      Japan.

PMID- 16101171
TI  - The efficacy of endoscopic mucosal resection in the diagnosis and treatment of
      group III gastric lesions.
AB  - BACKGROUND: The efficacy of endoscopic mucosal resection (EMR) in diagnosing and
      treating group III lesions was analyzed. PATIENTS AND METHODS: Forty-three
      patients, with group III lesions confirmed by histopathological examination of
      the biopsy specimens, were included. All of these patients underwent EMR. The
      final diagnosis after EMR broadly classified the lesions as adenocarcinoma or
      adenoma. The clinicopathological features and therapeutic results were analyzed.
      RESULTS: Adenocarcinoma was identified in 16 patients (37.2%) and adenoma in 27
      patients (62.8%). There were no differences in gender, age, lesion site,
      macroscopic type, or maximum diameter between the two groups. A significant
      difference in the maximum diameter of elevated lesions (p<0.05) was found between
      adenocarcinomas and adenomas, with the elevated lesions of adenocarcinomas
      measuring more than 10 mm. No residual focus recurrence was found among the
      adenomas. CONCLUSION: We conclude that EMR is effective and useful in diagnosing
      and treating group III lesions.

PMID- 16101172
TI  - Survival in untreated early stage non-small cell lung cancer.
AB  - BACKGROUND: The aim of this study was to determine the survival of untreated
      stage I and II in non-small cell lung cancer (NSCLC) patients. PATIENTS AND
      METHODS: A retrospective analysis of medical charts of all patients diagnosed
      with early stage NSCLC, between January 1990 and December 2001, was conducted and
      patients who were not treated were identified. Data on patient's age, gender,
      stage of the disease, pathology, reason for non-treatment and cause of death were
      reviewed. RESULTS: Thirty-nine patients with untreated stage I and II NSCLC were
      identified. The median age at diagnosis was 77 years; 66.7% were men and 33.3%
      were women. All patients were Caucasian and 66.7% had stage I disease, 46.2% had
      squamous cell carcinoma, while adenocarcinoma was found in 28.2%. The major
      reason for non treatment was chronic obstructive pulmonary disease (64.1%) and
      the main cause of death was metastatic disease (48.7%). The overall mean survival
      was 11.9 months. The mean survival at stage I was not statistically different
      from the mean survival at stage II (13.7 months vs. 8.4 months) (p < 0.12).
      CONCLUSION: Patients with untreated early stages NSCLC have a very poor
      prognosis. Alternative therapies that are better tolerated should be investigated
      in these patients with early stage NSCLC who cannot be offered standard
      treatment.

PMID- 16101173
TI  - Proptosis and decreased vision secondary to prostate cancer orbital wall
      metastasis.
AB  - The case of a 66-year-old gentleman who presented with unilateral proptosis, eye
      pain and partial loss of vision seven years after his original prostate cancer
      diagnosis is reported. MRI of the orbits revealed a 2-cm lesion in the
      posterolateral right orbital wall near the optic foramen with compression of the
      optic nerve. Metastatic orbital lesions are relatively uncommon in prostate
      cancer. Treatment is palliative and varies according to the time of presentation
      in the course of the disease. This patient's symptoms resolved after reinitiation
      of combined androgen blockade.

PMID- 16101174
TI  - Immunohistochemical expression of receptor-tyrosine kinase c-kit protein and TGF
      beta1 in invasive ductal carcinoma of the pancreas.
AB  - BACKGROUND: The receptor tyrosine kinase c-kit is known to play an important role
      in the progression of gastrointestinal stromal tumors, but its biological
      significance in other solid malignancies is unclear. Recent publications have
      suggested a regulatory role for TGF-beta1 in c-kit-mediated cell growth. The
      present study assessed the clinicopathological significance of c-kit protein
      (KIT) and TGF-beta1 expression in resectable invasive ductal carcinomas (IDCs) of
      the pancreas. PATIENTS AND METHODS: This study included 91 pancreatic IDC
      patients who received a pancreatectomy between 1982 and 2003. The expression of
      KIT and TGF-beta1 was analyzed by immunohistochemistry. RESULTS: KIT and TGF
      beta1 were expressed in 77% (70/91) and 59% (54/91) of the IDC, respectively. The
      expression of KIT was not correlated with that of TGF-beta1. TGF-beta1 expression
      correlated inversely with nodal involvement, but KIT expression did not correlate
      with any clinicopathological factors. KIT expression had no significant influence
      on the survival of the patients, whereas the survival rate of TGF-beta1 (+) IDC
      patients was significantly higher than that of TGF-beta1 (-) IDC patients. Co
      expression analysis of KIT and TGF-beta1 indicated that, in patients with KIT (+)
      IDC, the TGF-beta1 (+) group showed a significantly better survival rate than the
      TGF-beta1 (-) group. Neither KIT expression nor TGF-beta1 expression had a
      significant effect on the efficacy of adjuvant chemotherapy (ACT). In
      multivariate analysis, TGF-beta1 expression was one of the significant variables
      for survival in IDC patients overall, but KIT expression was not. CONCLUSION: TGF
      beta1 expression is suggested to have a significant influence on c-kit-mediated
      cell proliferation in human pancreatic IDCs.

PMID- 16101175
TI  - Nail disorders in a woman treated with ixabepilone for metastatic breast cancer.
AB  - Ixabepilone (Ix) (BMS-247550) is a potent member of a new class of microtubule
      stabilizing cytotoxic agents known as epothilones. In pre-clinical studies, Ix
      has shown anticancer activity against several cancer types, including paclitaxel
      resistant models, both in vitro and in vivo. The major toxicities associated with
      Ix are myelosuppression, sensory neuropathy and neutropenia. Other minor side
      effects include asthenia/fatigue, stomatitis, anorexia, alopecia, skin reaction,
      hypersensitivity reactions and a fluid-retention syndrome. Although Ix is
      functionally correlated to taxanes, no previous evidence exists regarding Ix
      related nail disorders. Here, we report a case of a 59-year-old woman treated
      with Ix at 40 mg/m2 day 1 q 21 days who, after 8 cycles of therapy, developed
      onycholysis and subungual hemorrhagic bullas in the fingernails.

PMID- 16101176
TI  - Expression of deltaNp63 in squamous cell carcinoma of the esophagus.
AB  - BACKGROUND: The p63 gene is present as two isoforms, namely TAp63 and deltaNp63.
      The biological role of deltaNp63 in the progression of esophageal cancer is still
      controversial. PATIENTS AND METHODS: The expression of deltaNp63, as well as that
      of p63, was immunohistochemically examined in 61 resected specimens of squamous
      cell carcinoma of the esophagus. RESULTS: The incidences of a positive deltaNp63
      expression were 32 and 64% in carcinomas with and without adventitial invasion,
      respectively, and 37 and 65% in those with and without lymph node metastasis,
      respectively (p<0.05). The prognosis was significantly better in the positive
      deltaNp63 group than in the negative group (p<0.01). However, a multivariate
      analysis revealed deltaNp63 not to be an independent prognostic factor. Regarding
      p63, diminished expression was more frequently observed in advanced carcinomas,
      however, there were no statistically significant differences. CONCLUSION: The
      impaired deltaNp63 reflects the progression of squamous cell carcinoma of the
      esophagus.

PMID- 16101177
TI  - Relationship between interleukin-12-expressing cells and antigen-presenting cells
      in patients with colorectal cancer.
AB  - BACKGROUND: Interleukin-12 (IL-12) is a powerful cytokine that plays an important
      role in cell-mediated immunity. Although IL-12 is produced by antigen-presenting
      cells (APCs), the relationship between IL-12 expression and APCs in colorectal
      cancer tissue remains unknown. PATIENTS AND METHODS: Immunohistochemical
      detection of APCs and IL-12 was performed in 22 colorectal cancer specimens. CD83
      and CD68 were used for the markers of mature dendritic cells (DCs) and
      macrophages, respectively. Double staining with CD83 or CD68 and IL-12 was also
      performed to detect IL-12-secreting cells. CD83-, CD68- and IL-12-positive-cell
      densities, clinicopathological factors and survival were analyzed. RESULTS: CD83
      , CD68- or IL-12-positive-cells were stained in the tumor stroma. Double-stained
      CD83/IL-12- or CD68/IL-12-positive-cells were also detected in the same area. The
      CD83-positive-cell density was significantly higher in patients with a high IL-12
      positive-cell density than those with a low IL-12-positive-cell density. The CD83
      positive-cell density was significantly lower in patients with T3-T4 depth of
      invasion, lymph node metastasis or tumors more advanced than stage II. The IL-12
      positive-cell density tended to be lower in patients with T3-T4 depth of invasion
      or venous invasion. Patients with high CD83- or IL-12-positive-cell density in
      their cancer specimens showed significantly better prognosis. CONCLUSION: This
      study provides new information on the significance of mature DCs, macrophages and
      IL-12-secreting cells in the local environment of colorectal cancer. Survival in
      patients with colorectal cancer was reflected by mature DCs and/or IL-12-positive
      cell density.

PMID- 16101178
TI  - Successful analysis of anticancer drug sensitivity by CD-DST using pleural fluid
      and ascites from patients with advanced ovarian cancer: case reports.
AB  - In vitro anticancer drug sensitivity tests have been performed for various types
      of cancers, and a relationship with clinical response has been observed. The
      collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is a new in
      vitro anticancer drug sensitivity test by Yabushita et al., recently reported to
      be useful in ovarian cancer. CD-DST allows analysis of a small number of cells,
      compared to other anticancer drug sensitivity tests. Here, we report a successful
      analysis of anticancer drug sensitivity by CD-DST using cancerous ascites and
      pleural fluid samples from 2 patients with advanced ovarian cancer. To our
      knowledge, this is only the second report of the application of CD-DST in ovarian
      cancer, and our results suggest that CD-DST could be helpful in the selection of
      anticancer drugs for neoadjuvant chemotherapy in advanced ovarian cancer.

PMID- 16101179
TI  - Brain metastases from epithelial ovarian cancer. The Hellenic Cooperative
      Oncology Group (HeCOG) experience and review of the literature.
AB  - BACKGROUND: Brain metastases from epithelial ovarian cancer (EOC) are rare. A
      retrospective study of all patients diagnosed with brain metastases from EOC over
      the last 20 years, according to the Hellenic Cooperative Oncology Group (HeCOG)
      tumor registry, was conducted. PATIENTS AND METHODS: A total of 1450 patients
      with EOC were treated within various HeCOG protocols from 1983 to 2004. Seventeen
      (1.17%) of them developed brain metastases. RESULTS: The median age at diagnosis
      of brain metastases was 58 years (range, 24 to 77). At initial diagnosis, 2
      patients had stage II, 12 had stage III and 3 had stage IV disease. Serous
      papillary adenocarcinoma was the most common histological subtype [12 patients
      (71%)]. All patients had received initial cisplatin-based chemotherapy. The
      median time from initial diagnosis to central nervous system (CNS) relapse was
      15.9 months (range, 1.4 to 70.8). The CNS was the only site of disease in 13
      (76.5%) patients, whereas 4 (23.5%) patients had additional extracranial disease.
      Two (12%) patients with isolated single brain lesions underwent surgical excision
      of the metastases, followed by whole brain radiation therapy (WBRT) and
      chemotherapy. Four (24%) patients were treated with WBRT alone, 6 (35%) patients
      with WBRT plus chemotherapy and 2 (12%) had only supportive care, while 3 (18%)
      patients decided not to have any further treatment after the diagnosis of brain
      metastases. The median survival time from diagnosis of CNS relapse was 5.7 months
      (range, 0.2 to 22.6) and the median survival time from diagnosis of EOC was 27.4
      months (range, 3.0 to 71.4). In patients with CNS recurrence as the only site of
      disease, the median survival time from diagnosis of CNS relapse was 5.3 months
      (range, 0.6 to 22.6) and in those with both CNS and extracranial disease, the
      median survival time was 3.9 months (range, 0.2 to 11.9) (p=0.5597). There was a
      statistically significant difference in survival for those treated with WBRT plus
      chemotherapy (10.0 months) versus those treated with WBRT alone (1.5 months) and
      those who had only supportive care (0.2 months) (p=0.0003). CONCLUSION: The
      incidence of cerebral metastases in our patients with EOC was 1.17%, which is
      consistent with the mean value of all series reported in the literature. The
      prognosis of patients with brain metastases from EOC is poor. Patients who had
      WBRT and chemotherapy fared better than those who received WBRT alone.

PMID- 16101180
TI  - Docetaxel in combination with irinotecan (CPT-11) in platinum-resistant
      paclitaxel-pretreated ovarian cancer.
AB  - The role of combination chemotherapy regimens in the management of ovarian cancer
      patients with tumors resistant to platinum compounds has not yet been defined.
      This multicenter prospective phase II study evaluated the activity and toxicity
      of the docetaxel-plus-irinotecan combination in ovarian cancer patients whose
      tumors were resistant to platinum compounds and who had been exposed to
      paclitaxel. Treatment consisted of docetaxel 60 mg/m2 i.v. followed by irinotecan
      200 mg/m2 i.v. both on day 1 followed by prophylactic recombinant human
      granulocyte-colony stimulating factor (rhG-CSF) support from days 2 to 6, every 3
      weeks. Thirty-one patients were enrolled in the study. The median age was 60
      years, and the median performance status (ECOG) was 1. Eight (26%) patients had
      primary tumors resistant to platinum, while the rest of the population had tumor
      recurrence within 6 months from the last cisplatin treatment. Four chemotherapy
      cycles per patient were administered, with the delivered dose intensity at 75% of
      the planned dose for both agents. Among 30 patients evaluable for response, there
      were 2 (7%) complete and 4 (14%) partial responses (overall response rate 20%;
      (95% confidence interval, CI, 11%-33%). Stable disease was recorded in 8 (28%)
      patients and progressive disease in 15 (51%). The median response duration was
      4.5 months (range, 3-12), the median time to progression 5 months (range, 2-17)
      and the median survival 11 months (range, 1-40); the 1-year survival was almost
      50%. Myelotoxicity was moderate, with grade 3 and 4 neutropenia occurring in 23%
      of the patients, grade 3-4 thrombocytopenia in 6% and febrile neutropenia in 13%.
      Grade 3 diarrhea was observed in 2% of the patients. There was one treatment
      related death due to sepsis. In conclusion, the combination of docetaxel plus
      irinotecan with rhG-CSF support, appears to be a moderately effective regimen
      with acceptable toxicity for platinum-resistant, paclitaxel-pretreated ovarian
      cancer patients. Further investigation in comparative studies is required to
      define the role of combination versus single agent chemotherapy in this group of
      patients.

PMID- 16101181
TI  - Superantigen-activated mononuclear cells induce apoptosis in transitional cell
      carcinoma.
AB  - BACKGROUND: Superantigens are among the most potent T-cell mitogens known. Since
      T-cell activation and T-cell-derived cytokines play a role in the immune response
      associated with intravesical Bacillus Calmette-Guerin (BCG) application, this
      study was initiated to explore the fundamental aspects of a potential new
      immunomodulatory therapy for superficial bladder cancer. Since Superantigen
      induced cytotoxicity is mediated by apoptosis, the effects of SEB (staphylococcal
      enterotoxin B)-Superantigen-activated PBMC (peripheral blood mononuclear cells)
      on bladder cancer cells were evaluated with regard to Fas/Fas-ligand-based
      interactions. MATERIALS AND METHODS: Whether SEB can induce Fas-ligand expression
      on PBMC and the extent of cytokine secretion were examined by flow cytometry and
      specific ELISA. In addition, whether the SEB-activated PBMC are able to induce
      apoptosis in transitional cell carcinoma cells (TCC) was evaluated in co-culture
      experiments. RESULTS: It was shown that SEB induced pronounced time- but not dose
      dependent specific Fas-ligand expression on PBMC, lasting 1 h to 7 h after
      initiation of the experiment. Cleaved soluble Fas-ligand was detected in the
      culture supernatants 24 h after stimulation, but not earlier. Further, a strong
      time-dependent secretion of cytokines IL-2, IFN-gamma and TNF-alpha released from
      the SEB-stimulated PBMC was shown. In co-culture experiments, it was demonstrated
      that SEB-activated PBMC significantly induced apoptosis in TCC cells. The
      released cytokines from SEB-treated PBMC demonstrated only a minor, not
      significant, apoptotic response in TCC cells. CONCLUSION: This first evaluation
      of the possible mode of action of a Superantigen opens the door for extended
      studies of this interesting approach to the treatment of bladder cancer.

PMID- 16101182
TI  - MUC1 peptide vaccination in patients with advanced pancreas or biliary tract
      cancer.
AB  - BACKGROUND: To evaluate the immunogenicity of MUC1 peptide vaccine in advanced
      pancreatic and bile duct cancers, a phase I clinical trial was conducted.
      MATERIALS AND METHODS: A 100-mer MUC1 peptide consisting of the extracellular
      tandem repeat domain and incomplete Freund's adjuvant were subcutaneously
      administered to 6 pancreatic and 3 bile duct cancer patients at weeks 1, 3 and 5
      and doses ranging from 300 to 3000 microg. Circulating intracytoplasmic cytokine
      positive CD4+ T cells and anti-MUC1 IgG antibodies were measured before and after
      vaccination. RESULTS: There were no adverse events, except for mild reddening and
      swelling at the vaccination site. In 8 patients eligible for clinical evaluation,
      7 had progressive disease and 1 stable disease with a tendency for increased
      circulating anti-MUC1 IgG antibody after vaccination. CONCLUSION: This phase I
      clinical trial revealed the safety of a vaccine containing 100-mer MUC1 peptides
      and incomplete Freund's adjuvant.

PMID- 16101183
TI  - Chemokines in human colorectal carcinoma.
AB  - BACKGROUND: Chemokines (CKs) may promote antitumor immunity in cancer, act as
      tumor growth factors, influence metastatic spreading or angiogenesis. The purpose
      of this study was to investigate whether CK expression is altered in colorectal
      carcinomas compared to normal mucosa and to elucidate its possible clinico
      pathological implications. MATERIALS AND METHODS: The levels of CCL2 (MCP-1),
      CCL4 (MIP-1beta), CCL5 (RANTES), CXCL 1 (GRO-alpha), CXCL 5 (ENA-78) and CXCL 8
      (IL-8) were investigated in 10 colorectal carcinomas and their corresponding
      normal mucosa by the use of ELISA. RESULTS: All CK analyzed, with the exception
      of CCL5 (RANTES), were expressed at a significantly higher level in malignant
      tissue. CONCLUSION: Therapeutic studies in colon carcinomas should, therefore,
      focus more on the neutralization of CKs than on their application.

PMID- 16101184
TI  - Treatment arms summarizing analysis of 220 high-grade glioma studies.
AB  - Large phase III studies have identified limited survival benefits with
      chemotherapy in high-grade glioma. However, numerous clinical trials have been
      published previously with smaller patient numbers and no control groups. A small
      positive effect could be missed this way, resulting in premature rejection of
      possible beneficial treatment. In order to perform a treatment arm summarizing
      analysis (TASA), a database was created summarizing treatments published between
      January 1976 and June 2002. In this database, one record represents a cohort of
      patients treated in the same way. Various patient cohort characteristics such as
      median age, and outcome measures including median overall survival times (mOS),
      were documented. Two-hundred and twenty publications were documented with a total
      number of 17,213 cases treated in 337 treatment groups. There was a statistically
      significant relationship between the distribution of histological grades
      (p<0.001) and the outcome, and a better outcome in younger patient populations
      (p<0.01). However, the known influence of the median Karnowsky performance scale
      could not be confirmed in this database. The extent of surgery showed a positive
      influence only when excluding relapse studies, while the positive effect of
      radiation was clear in all subgroups (p<0.05). Clinical studies that included
      nitrosurea in the treatment had a significantly better outcome than those with
      platinum drugs or without chemotherapy. We conclude that TASA, representing a
      novel way to perform a meta-analysis, is valid since it confirms the known
      treatment effects and, therefore, has the potential to provide new insights by
      combining information from different clinical treatment studies.

PMID- 16101185
TI  - Expression of vascular endothelial growth factor and its receptor, KDR/Flk-1, in
      soft tissue sarcomas.
AB  - The aim of the present study was to evaluate the association of vascular
      endothelial growth factor (VEGF) and its receptor, KDR/Flk-1, with tumor grade,
      microvessel density (MVD) and clinical outcome in patients with soft tissue
      sarcomas (STSs). Tissue specimens of 28 patients with STSs were analyzed
      immunohistochemically using specific monoclonal antibodies. Tissue samples were
      obtained prior to any treatment. Half of the STSs exhibited strong expression of
      VEGF that was associated statistically significantly with high tumor grade.
      Strong expression of KDR/Flk-1 was detected in only 2 sarcomas. No association
      was demonstrated between VEGF and KDR/Flk-1 expression. MVD was significantly
      associated with tumor grade and was higher in sarcomas with strong VEGF
      expression. Limited data on clinical outcome precluded solid analyses for an
      association with disease progression. This study provides further evidence on the
      role of VEGF and MVD in tumor aggressiveness in STSs.

PMID- 16101186
TI  - A phase II study of tamoxifen in hormone-resistant metastatic prostate cancer:
      possible relation with prolactin secretion.
AB  - Recent experimental observations, showing the potential role of prolactin (PRL)
      as a tumor growth factor for prostate cancer and the unfavourable prognostic
      significance of enhanced chromogranin-A-secreting neuroendocrine cell
      proliferation, could contribute to a better understanding of the mechanisms
      responsible for the occurrence of hormone-resistance in the prostate cancer.
      Moreover, it has been shown that tamoxifen, which consistently exerts estrogenic
      activity in males, may inhibit prostate cancer cell proliferation in experimental
      studies. At present, there are no clinical data in humans. This preliminary phase
      II study was planned in an attempt to evaluate the therapeutic efficacy of
      tamoxifen in hormone-refractory metastatic prostate cancer. The study included 14
      consecutive metastatic prostate cancer patients, who had progressed under the
      classical endocrine therapy with LHRH-analogs and/or anti-androgens. Patients
      received the same treatment plus tamoxifen at 20 mg/day orally. A decline greater
      than 50% in prostate-specific antigen (PSA) levels occurred in 4/14 (29%)
      patients within the first 2 months of therapy, with a median duration of 5
      months. Mean pre-treatment levels of PRL were significantly higher in responder
      patients than in those who progressed. Moreover, abnormally high pre-treatment
      levels of PRL were found in 5/14 (36%) patients. The percent of clinical
      responses observed in patients with pre-treatment hyperprolactinemia was
      significantly higher than that found in patients with normal pre-treatment PRL
      concentrations. Finally, a significant decline in mean PRL levels upon tamoxifen
      therapy occurred only in the responder patients. This preliminary study seems to
      justify further clinical research to confirm the potential efficacy of tamoxifen
      in the treatment of hormone-refractory prostate cancer and to identify possible
      parameters, which may predict the response to treatment.

PMID- 16101187
TI  - Serum carcinoembryonic antigen level in pN1 non-small cell lung cancer patients.
AB  - BACKGROUND: Although the prognostic significance of the serum carcinoembryonic
      antigen (CEA) level in non-small cell lung cancer has been reported in several
      studies, it is unknown whether the serum CEA level is a prognostic determinant
      for pN1 disease or not. MATERIALS AND METHODS: Seventy patients with pN1 non
      small cell lung cancer who received complete resection were reviewed. The
      preoperative serum CEA level was measured in all patients. RESULTS: The pN1
      patients with pT2-4 disease, hilar node involvement, multiple N1 station and
      elevated serum CEA level (>5 ng/mL) had a significantly unfavorable prognosis.
      Although a serum CEA level higher than 5 ng/mL was not an independent prognostic
      determinant, more than 10 ng/mL was an independent factor by multivariate
      analysis. In patients with pT1-2N1 disease, a serum CEA level more than 10 ng/mL
      was also a prognostic determinant. CONCLUSION: An elevated serum CEA level,
      especially higher than 10 ng/mL, is a significant prognostic determinant for pN1
      lung cancer patients.

PMID- 16101188
TI  - Bisphosphonate treatment does not affect serum levels of osteoprotegerin and
      RANKL in hypercalcemic cancer patients.
AB  - Bisphosphonates are the standard treatment for hypercalcemia of malignancy. We
      hypothesized that bisphosphonate treatment and the subsequent fall in serum
      calcium might induce changes in the RANK/RANKL/OPG system, which plays a pivotal
      role in the regulation of bone resorption. Soluble RANKL and OPG levels were
      measured in the serum of 15 hypercalcemic patients at baseline and on 5
      consecutive days following treatment with the amino-bisphosphonate ibandronate.
      At day 0, the median soluble OPG level was elevated (p=0.0021) in the
      hypercalcemic group as compared to normal controls, while the median serum RANKL
      level was not significantly different. Ibandronate treatment and the resulting
      decrease (p<0.0001) in serum calcium levels did not affect the serum
      concentrations of OPG, serum RANKL, or the serum RANKL/OPG ratio. In comparison
      with day 0, these factors did not change significantly at any time-point
      analyzed.

PMID- 16101189
TI  - Radiotherapy and razoxane in advanced bile duct carcinomas.
AB  - OBJECTIVES: Little is known about the radiation sensitivity of bile duct
      carcinomas. The current study was undertaken to prospectively assess the
      objective response rates in bile duct carcinomas treated with radiotherapy and
      razoxane. MATERIALS AND METHODS: Twenty-three patients with advanced cancer of
      the biliary tree were irradiated together with the radiosensitizer razoxane at a
      dose of 125 mg twice daily by mouth. There were 16 females and 7 males, median
      age 68 years. They received a total tumor dose of 48 Gy (range 1.7-60) at the
      ICRU point with single fractions of 1.7 to 2 Gy. RESULTS: Among the 23 patients,
      14 had measurable disease. Objective tumor responses were seen in 4/4 gallbladder
      carcinomas (1 CR, 3 PR), 4/5 extrahepatic cholangiocarcinomas (2 CR 2 PR), and
      1/5 hepatobiliary cancers (1 PR), leading to an overall response rate of 64%. The
      tumors remained locally controlled in 12 out of 16 assessable patients (75%). On
      an intention-to-treat basis, all patients with different biliary cancer without
      distant metastases had a median-survival time of 10 months (range 1 to 48) from
      the start of the radiotherapy; the 1-year survival was 43%. No patient survived
      beyond 4 years. Tolerance to the treatment was fairly good. Nausea and vomiting
      of grade 1 and 2 (WHO) was noted in 61%, and reversible leukopenia of grade 3 and
      4 in 9% of the cases. The rate of inherent complications was high. CONCLUSION:
      Combined radiotherapy and razoxane led to local response rates which are superior
      to data from the literature when radiotherapy alone is used. Obstacles to the
      treatment were complications of the disease and frequent metastasis.

PMID- 16101190
TI  - Clinical experience with bevacizumab in colorectal cancer.
AB  - Angiogenesis, the process of generating new capillary blood vessels, is a
      fundamental requirement for normal physiological processes including
      embryogenesis, reproductive function and wound healing. Angiogenesis is also
      implicated in various pathological conditions including age-related retinal
      macular degeneration, diabetic retinopathy, rheumatoid arthritis, psoriasis and
      cancer growth and metastasis. Vascular endothelial growth factor (VEGF) is one of
      the best characterized of the pro-angiogenic growth factors, and multiple
      strategies have been developed to inhibit this pathway. Bevacizumab, a monoclonal
      antibody developed against VEGF, has shown initial preclinical and clinical
      activity. This review discusses the critical role of VEGF and summarizes the
      available data on the use of bevacizumab in colorectal cancer.

PMID- 16101191
TI  - Adjusted carbohydrate antigen 19-9. Correlation with histological grade in
      pancreatic adenocarcinoma.
AB  - BACKGROUND: The serum level of carbohydrate antigen 19-9 (CA 19-9) depends on the
      tumor size and differentiation grade. Jaundice can cause an elevation of serum CA
      19-9, although the nature of this interaction is not fully understood. PATIENTS
      AND METHODS: This was a retrospective study of 26 patients with potentially
      resectable pancreatic adenocarcinoma. Serum CA 19-9 was correlated with the
      histological differentiation. CA 19-9 adjusted for serum bilirubin was determined
      and analyzed. RESULTS: No correlation between CA 19-9 and histological
      differentiation was determined (p>0.05). The median adjusted CA 19-9 level was
      significantly lower (p=0.01) in patients with normal biliary excretion than those
      with bilirubin levels >2 mg/dL. CONCLUSION: These data are consonant with the
      theory of a dual contribution to the serum CA 19-9 level from biliary obstruction
      and tumor cell synthesis.

PMID- 16101192
TI  - Molecular markers in gastric cancer: can p53 and bcl-2 protein expressions be
      used as prognostic factors?
AB  - BACKGROUND: The prognostic value of p53 and bcl-2 protein expressions in gastric
      cancer is still unclear, as shown by the discordant results still reported in the
      literature. PATIENTS AND METHODS: In this study, p53 and bcl-2 protein
      expressions were investigated by immunohistochemistry and correlated with various
      clinicopathological parameters and survival, in a series of 52 gastric cancer
      patients who underwent potentially curative gastrectomy. RESULTS: p53 expression
      was observed in 34 patients (65.4%) and was significantly correlated with the
      intestinal type of cancer (p=0.018). Bcl-2 expression was detected in 12 patients
      (23.1%) and inversely correlated with lymph node metastasis (p=0.042) and tumour
      grade (p=0.024). There was a statistically significant inverse relationship
      between p53 and bcl-2 expression (p=0.014). Moreover, p53 and bcl-2 protein
      expressions had no significant influence on overall survival. CONCLUSION: These
      results suggest that the expression of p53 and bcl-2 proteins has no significant
      impact on the outcome of patients with gastric cancer.

PMID- 16101193
TI  - Bevacizumab as treatment for chemotherapy-resistant pancreatic cancer.
AB  - A 74-year-old male, with refractory stage IV pancreatic cancer, was successfully
      treated with bevacizumab 5 mg/kg and combination chemotherapy consisting of
      gemcitabine, fluorouracil leucovorin, irinotecan and cisplatin (GFLIP) every two
      weeks. The patient had rapidly failed initial treatment with GFLIP given in an
      identical dose and schedule. Large new liver lesions developed during active
      treatment. On adding bevacizumab to GFLIP, serial measures on CT confirmed an
      objective (RECIST) response. The tumor marker CA19-9 fell rapidly from 24,000
      U/ml to less than 400 U/ml. This was accomplished with clinically inconsequential
      side-effects. This is the first demonstrated benefit of bevacizumab used in
      combination with previously failed chemotherapy for pancreatic cancer.

PMID- 16101194
TI  - The value of the ImmunoCyt/uCyt+ test in the detection and follow-up of carcinoma
      in situ of the urinary bladder.
AB  - BACKGROUND: Urine bound tests, which have been developed for the early detection
      of urothelial cancer (UC), do not seem to match cytology in the detection of
      carcinoma in situ (CIS) as their sensitivity in the case of CIS is poor.
      ImmunoCyt/uCyt+ in CIS seems promising, but the number of analysed CIS is still
      small. The aim of the present study was to assess the value of this test in the
      detection and follow-up of carcinoma in situ of the urinary bladder. PATIENTS AND
      METHODS: Thirty-five patients, with histologically verified CIS of the urinary
      bladder, were included in the study. At the first diagnosis, patients underwent
      cytology, cystoscopy, bioptical bladder mapping and ImmunoCyt/uCyt+. All patients
      underwent BCG instillation therapy. The patients were followed with cytology,
      ImmunoCyt/uCyt+, cystoscopy and bladder mapping after every BCG cycle and then
      every 3 months. RESULTS: At the first CIS diagnosis, the sensitivity of cytology
      and ImmunoCyt/uCyt+ was 100%. At the first control after therapy, cytology
      detected 81.8% of recurrences and ImmunoCyt/uCyt+ detected 90.9%. At the second
      control, both tests each detected 50% of recurrences. At every control, the
      combination of both the tests together gave a sensitivity of 100%. The
      specificity of cytology after therapy improved from 88.2% at the first control up
      to 100% at the third control. The specificity of ImmunoCyt/uCyt+ after BCG
      initially decreased from 70.6% to 55.5% and finally increased to 88.9%.
      CONCLUSION: ImmunoCyt/uCyt+ is as sensitive as cytology in the first diagnosis of
      CIS. In the follow-up, even if it is less sensitive, its combination with
      cytology leads to detection of 100% of the recurrences. Despite decreasing
      specificity after therapy, the value remains acceptable and increases during
      maintenance therapy. The ImmunoCyt/uCyt+ test could play an important role in
      controlling the response of patients to instillation therapies or in the
      modification of their application schedules.

PMID- 16101195
TI  - Urinary levels of vascular endothelial growth factor in patients with prostate
      cancer as a predictor of disease progression.
AB  - BACKGROUND: The objectives of this study were to investigate the association
      between urinary levels of vascular endothelial growth factor (VEGF) and the
      progression of prostate cancer, and to evaluate changes in urinary VEGF levels
      before and after initial treatment. MATERIALS AND METHODS: A total of 97 patients
      with prostate cancer were included in this study. Of these 97, 52 underwent
      radical prostatectomy and the remaining 45 received hormonal therapy as initial
      treatment. Urinary VEGF levels were measured using a sandwich enzyme immunoassay,
      and the results were analyzed with respect to several clinicopathological
      factors. RESULTS: The mean urinary level of VEGF in patients with prostate cancer
      was significantly higher than that in healthy controls. The urinary level of VEGF
      in prostate cancer patients with metastasis was significantly elevated compared
      with that in those without metastasis. Among 52 patients who underwent radical
      prostatectomy, the urinary levels of VEGF in patients with pathologically organ
      confined disease were significantly lower than that in those with extraprostatic
      disease. Furthermore, the urinary VEGF level in 52 patients after radical
      prostatectomy was significantly lower than that before radical prostatectomy,
      while there was no significant difference in urinary VEGF level in 45 patients
      before and after hormonal therapy. CONCLUSION: These findings suggest that the
      elevation of urinary VEGF could be a useful predictor of disease progression in
      prostate cancer, and that the urinary levels of VEGF reflect the therapeutic
      effect of radical prostatectomy, but not that of hormonal therapy.

PMID- 16101196
TI  - Use of natriuretic peptides for detecting cardiac dysfunction in long-term
      disease-free breast cancer survivors.
AB  - BACKGROUND: Plasma natriuretic peptides are increased in patients with cardiac
      dysfunction. N-terminal (NT-ANP) and B-type (BNP) natriuretic peptides were
      measured in disease-free breast cancer survivors, during long-term follow-up
      after epirubicin (360 mg/m2 or 450 mg/m2 cumulatively) and chest irradiation.
      PATIENTS AND METHODS: Plasma samples for natriuretic peptide measurement were
      repeated after extended follow-up in 54 patients, who had participated in 2
      studies evaluating cardiotoxicity. RESULTS: From a median follow-up of 2.7 to 6.5
      years, median BNP was raised almost three-fold (p<0.001). Symptomatic heart
      failure was now present in 2 patients. Compared to the epirubicin 360 mg/m2
      group, BNP was higher (p=0.006) in the 450 mg/m2 group, with a trend (p=0.054)
      for higher NT-ANP. CONCLUSION: These findings suggest that anticancer therapy
      initiates an autonomically progressive process that may ultimately lead to
      symptomatic cardiac dysfunction, years after treatment. BNP measurement may be of
      value to identify patients requiring intensive cardiac follow-up.

PMID- 16101197
TI  - Effects of imatinib mesylate on adenoid cystic carcinomas.
AB  - BACKGROUND: Adenoid cystic carcinomas (ACCs) are rare tumors which most often
      arise in the salivary glands. They have a propensity for local relapse and tend
      to metastasize, frequently with a protracted clinical course. A substantial
      fraction of the tumors expresses c-Kit or the platelet-derived growth factor
      receptor beta (PDGFRbeta), both targets for imatinib mesylate. No standard
      systemic therapy is known for these neoplasms. PATIENTS AND METHODS: c-kit and
      PDGFRbeta-expression were determined by immunohistochemistry. Four patients with
      distant metastases and with at least one positive result were treated with 400 mg
      imatinib mesylate once daily and their response assessed. RESULTS: c-Kit and
      PDGFRbeta expressions were variable among the tumor samples. Toxicity was mild.
      No remissions were observed. CONCLUSION: These data support that c-Kit or
      PDGFRbeta expression per se are not prognostic for the therapeutic response of
      metastasized ACCs to imatinib mesylate.

PMID- 16101198
TI  - The efficacy of MRI with ultrasmall superparamagnetic iron oxide particles
      (USPIO) in head and neck cancers.
AB  - BACKGROUND: The objective was to evaluate the diagnostic accuracy of ultrasmall
      superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI)
      compared to plain MRI in patients with a clinical N+ neck using histology as a
      gold standard. MATERIALS AND METHODS: Twenty-eight patients underwent unenhanced
      and USPIO-enhanced MRI using T1-weighted spin echo (SE) sequences and high
      resolution Turbo-Spin-Echo (TSE) T2-weighted sequences, as well as T2-weighted
      Gradient Echo (GE) sequences in axial and sagittal slice orientation. The signal
      intensity (SI) decrease was measured by a region of interest evaluation and
      visual analysis was performed. RESULTS: Histopathological evaluation of 363 lymph
      nodes revealed 34 as metastatic. USPIO MRI detected 28 metastases (sensitivity
      82.3%) and 329 non-metastatic lymph nodes (specificity 100%). Regarding lymph
      node size, USPIO MRI was correct in all patients who underwent surgery. One lymph
      node with microinfiltration of tumor cells was detected by USPIO MRI. CONCLUSION:
      There were no side-effects during or after application of the contrast agent.
      This study confirms the efficacy of MRI with USPIO in patients with head and neck
      cancer. USPIO-enhanced MRI could have an important effect on surgery planning.
      Because of its high specificity, USPIO-enhanced MRI seems to be a diagnostic
      modality able to differentiate borderline-sized lymph nodes.

PMID- 16101199
TI  - Mesothelioma: treatment and survival of a patient population and review of the
      literature.
AB  - BACKGROUND: Our purpose was to evaluate the survival of patients with pleural and
      intraperitoneal malignant mesothelioma and, particularly, to estimate the
      efficacy of chemotherapy as well as radiotherapy and surgery. A review of the
      literature with respect to these parameters is included. PATIENTS AND METHODS:
      Thirty-five patients with malignant mesothelioma (28 with pleural and 7 with
      intraperitoneal) were enrolled. Twenty-eight patients underwent chemotherapy,
      7/35 radiation and 9/35 surgery (2 with pleural and 7 with abdominal disease).
      Combination chemotherapy included cisplatin-gemcitabine, cisplatin (or
      carboplatin) with premetrexed and doxorubicin-cyclophosphamide. RESULTS: In 2/28
      patients with pleural mesothelioma the tumor was excised and in 7 with
      intraperitoneal disease, surgical therapy was palliative and there was survival
      prolongation. Radiotherapy was only palliative. Chemotherapy produced a very low
      response: 2/28 (7.14%) patients achieved a partial response. The median survival
      was 17 months, 4-year survival, 24.4% and 5-year survival, 12.12%. No serious
      toxicity was observed. CONCLUSION: Malignant mesothelioma of the pleura and
      intraperitoneum is a slow-growing disease which is indicated by the long
      survival, despite the failure of chemotherapy, radiation therapy and surgery.

PMID- 16101200
TI  - [Measuring to improve the performance of the Mexican health system].

PMID- 16101201
TI  - [Prevalence and diagnosis of depression in Mexico].
AB  - OBJECTIVE: To present the prevalence of depressive episodes, as well as the
      percentage of the population with medical diagnosis. MATERIAL AND METHODS: The
      definition of depression was based on a schedule with DSM IV diagnostic criteria.
      Using data from the 2002-2003 National Assessment Performance Survey, the
      prevalence of depression was estimated at the national level, by sex, age,
      education, size of residence community, and state. The percentage of individuals
      with medically diagnosed depression and the percentage of those under treatment
      were also estimated. RESULTS: The national prevalence of depression was 4.5%:
      5.8% in women and 2.5% in men. The prevalence of depression increased with age
      and decreased with higher education. Among males, the prevalence was higher in
      rural than urban communities. A large percentage of affected individuals have no
      medical diagnosis. CONCLUSIONS: Depression is a frequent disease in adults.A
      higher prevalence is associated with social vulnerability. The low percentage of
      diagnosis represents a challenge for mental health service planning and
      provision.

PMID- 16101202
TI  - [Responsiveness of the Mexican health system].
AB  - OBJECTIVE: To present and discuss findings on the responsiveness of the Mexican
      health system. MATERIAL AND METHODS: The data source was the 2002-2003 National
      Performance Assessment Survey. A descriptive analysis was performed and results
      were adjusted for user's expectations using vignette information. Final results
      were disaggregated by sex, provider, age, and education level. RESULTS:
      Responsiveness scores given by women and senior individuals were higher than
      those provided by men and young adults. Major differences were observed when
      provider comparisons were made. In ambulatory care, the Ministry of Health and
      private providers were better rated than major social security institutions. For
      in-patient care, private providers were better rated than public health
      institutions. CONCLUSIONS: Responsiveness of the Mexican health system requires
      improvements in certain areas in order to meet one of the basic goals of all
      health systems.

PMID- 16101203
TI  - [Medical insurance coverage in Mexico].
AB  - OBJECTIVE: To present estimates of health insurance coverage in Mexico and
      discuss the differences among some sources of information. MATERIAL AND METHODS:
      Based on a national survey performed in 2002, the percentage of insurance
      coverage was estimated by state, rural condition, and expenditure level. RESULTS:
      The percentage of the population without medical insurance is 59.9%. The main
      insurance institution is the Mexican Institute for Social Security (Instituto
      Mexicano del Seguro Social, IMSS), with a coverage of 29.5%. Private insurance
      agencies cover 1.5% of the total population. There are huge differences in
      insurance coverage by state, expenditure level and social exclusion level.
      CONCLUSIONS: Data on insurance coverage provided by Mexico's main social security
      institution differ from that obtained through population-based studies. Some of
      these differences may be due to probabilistic reasons and others to macroeconomic
      changes. However, these reasons had not been sufficiently explored. In depth
      studies are needed in order to explain the observed differences.

PMID- 16101204
TI  - [Private expenditure in health by state in Mexico].
AB  - OBJECTIVE: Present information on the magnitude and composition of private health
      expenditure (PHE) in Mexico. MATERIAL AND METHODS: Total PHE by state was
      calculated using the System of National Health Accounts and National Performance
      Assessment Survey 2002-2003 by means of elasticities and growth relative
      contributions. RESULTS: 58% of the total PHE was private and 90% of this was out
      of-pocket expenditure. Most of the latter is expenditure in ambulatory care and
      drugs. 60% of the PHE was concentrated in only six states. PHE was lower than
      public expenditure in six states. CONCLUSIONS: The magnitude of out-of-pocket
      expenditure in health is worrying, since it is the most unfair, inefficient and
      regressive way of financing health care. Health authorities should look for
      alternative ways to finance health care, like the Popular Health Insurance.

PMID- 16101205
TI  - [Catastrophic health expenditures in Mexico: magnitude, distribution and
      determinants].
AB  - OBJECTIVE: To describe the magnitude, distribution, and determinants of
      catastrophic health expenditures in Mexico. MATERIAL AND METHODS: The information
      source was the National Performance Assessment Survey and the methodology, the
      one developed by the World Health Organization for assessing fair financing.
      Households with catastrophic expenditures were defined as those with health
      expenditures over 30% of their ability to pay. Multivariate analysis by logistic
      and linear regression were used to identify the determinants of catastrophic
      expenditures. RESULTS: A total of 3.8% of the households incurred in catastrophic
      health expenditures. There were huge differences by state. The uninsured, poor,
      and rural households showed a higher impoverishment risk. Sixty percent of the
      catastrophic expenditures were attributable to outpatient care and medication. A
      10% increase of insured households could result in a 9.6% decrease in
      catastrophic expenditures. Disability, adults 60 years of age and older, and
      pregnancy increased the probability of catastrophic expenditures. CONCLUSIONS:
      The insurance of older adults, pregnant women, and persons with disabilities
      could reduce catastrophic health expenditures in Mexico.

PMID- 16101206
TI  - [Catastrophic health expenditures in Mexico: comparative study by social
      exclusion level].
AB  - OBJECTIVE: To describe the differences in catastrophic health expenditures in
      five Mexican states. MATERIAL AND METHODS: This study included five states
      selected by convenience according to their social exclusion level. Household
      catastrophic health expenditures attributable to the three components of out of
      pocket health expenditures (ambulatory care, medication, and inpatient care) were
      calculated. RESULTS: The risk of impoverishment at the national level was greater
      in the most vulnerable households, namely, in the 20% poorest, rural, and
      uninsured households. Nevertheless, in states like Aguascalientes, Guerrero,
      Sinaloa, and Morelos the results were different. Over 70% of catastrophic health
      expenditures were attributable to medication and outpatient care expenditures in
      the poorest states. CONCLUSIONS: The differences found among states show that the
      implementation of local health policies to reduce catastrophic health
      expenditures should be based on evidence generated from analyses at the state
      level.

PMID- 16101207
TI  - [Fair health financing and catastrophic health expenditures: potential impact of
      the coverage extension of the popular health insurance in Mexico].
AB  - OBJECTIVE: To assess the impact on fair health financing and household
      catastrophic health expenditures of the implementation of the Popular Health
      Insurance (Seguro Popular de Salud). MATERIAL AND METHODS: Data analyzed in this
      study come from the National Income and Expenditure Household Survey (Encuesta
      Nacional de Ingresos y Gastos de los Hogares, ENIGH), 2000, and the National
      Health Insurance and Expenditure Survey, (Encuesta Nacional de Aseguramiento y
      Gasto en Salud, ENAGS), 2001. Estimations are based on projections of extension
      of the Popular Health Insurance under different conditions of coverage and out-of
      pocket expenditure reductions in the uninsured population. The mathematic
      simulation model assumes applying the new Popular Health Insurance financial
      structure to the 2000 expenditure values reported by ENIGH, given the probability
      of affiliation by households. RESULTS: The model of determinants of affiliation
      to the Popular Health Insurance yielded three significant variables: being in
      income quintiles I and II, being a female head of household, and that a household
      member had a medical visit in the past year. Simulation results show that
      important impacts on the performance of the Mexican Health System will occur in
      terms of fair financing and catastrophic expenditures, even before achieving the
      universal coverage goal in 2010. A reduction of 40% in out-of-pocket expenditures
      and a Popular Health Insurance coverage of 100% will decrease catastrophic health
      expenditures from 3.4% to 1.6%. CONCLUSIONS: Our results show that the reduction
      of out-of-pocket expenditures generated by the new financing and health provision
      Popular Health Insurance model, will improve the financial fairness index and the
      financial contribution to the health system, and will decrease the percentage of
      households with catastrophic expenditures, even before reaching universal
      coverage. A greater impact may be expected due to coverage extension initiating
      in the poorest communities that have a very restricted and progressive financial
      contribution.

PMID- 16101208
TI  - [Methods of the Mexican National Performance Assessment Survey].
AB  - OBJECTIVE: To describe the sampling design, operative strategy, and data
      management used in the Encuesta Nacional de Evaluaci6n del Desempeno (Mexican
      National Performance Assessment Survey). MATERIAL AND METHODS: A probabilistic,
      multistage, stratified sample was used to make inferences for each state of the
      country with representativeness of the urban and rural localities of Mexico. The
      survey was conducted between November 2002 and April 2003. The study population
      consisted of individuals in their households. RESULTS: Forty-thousand households
      were visited all over the country, and 38,746 interviews were obtained,with a non
      response rate considerably lower than expected. CONCLUSIONS: The methods used to
      carry out the National Performance Assessment Survey allowed calculation of
      estimates with measurable accuracy in terms of error and confidence, making the
      results inferable to the national population.

PMID- 16101209
TI  - [Performance assessment indicators, Mexico 2002].

PMID- 16101210
TI  - Want your QI program to succeed? Keep your eye on the fundamentals.
AB  - If key stakeholders are not involved in the planning process, they will not
      participate in the change initiative. Make sure key participants understand the
      relationship between processes and subprocesses. Stakeholders are more difficult
      to engage than process owners, say the experts.

PMID- 16101211
TI  - Study raises concerns on public reporting of data.
AB  - Comprehensive risk adjustment uncovers discrepancies between patients in New York
      and Michigan. Michigan angioplasty patients had a significantly higher incidence
      of kidney problems, diabetes, lung disease, and vascular problems. The majority
      of physicians surveyed said their patient selection was affected by public
      reporting.

PMID- 16101212
TI  - Home-grown CDR draws high utilization and award.
AB  - Provider access to clinical data on patients significantly enhanced through
      comprehensive database. Database was developed over period of years, gradually
      adding components as needs are seen. Duplication of tests is eliminated; more
      patients are referred appropriately to disease management programs.

PMID- 16101213
TI  - New P4P program uses established measures.
AB  - Leapfrog has designed its program to reward improvers as well as best performers.
      Key areas represent approximately 33% of admissions and 20% of commercial payers'
      inpatient expenditures. Local market conditions, employer groups, and health
      plans will dictate incentive structures.

PMID- 16101214
TI  - Integration software saves thousands of hours.
AB  - After a merger, the hospital was required to merge 140,000 patient records into
      the pre-existing system. Actions improve patient safety and confidentiality by
      ensuring access to the right patient data. Single project saves more than
      $40,000; ongoing billing updates take 20 minutes per day.

PMID- 16101215
TI  - [Clinical features of Barrett's esophagus].

PMID- 16101216
TI  - [Preface: Recent perspectives of the Barrett's esophagus].
AB  - As the prevalence of reflux esophagitis is increasing in Japan, due to increased
      amount of energy intake and improved hygiene with the reduced H. pylori
      infection, the number of patients having Barrett's esophagus is also increasing.
      In the Western countries, adenocarcinoma of the esophagus is rapidly increasing
      among the white elder male, where the reflux esophagitis is more common.
      Terminology of Barrett's esophagus is still confusing. Recent proposal of
      endoscopic evaluation of Barrett's esophagus is based on the endoscopic findings,
      not histologic findings. In the development of adenocarcinoma of the esophagus,
      several steps of genetic abnormalities might be involved. We still do not know
      whether we may experience an increase of adenocarcinoma of the esophagus in Japan
      or not.

PMID- 16101217
TI  - [The definition of Barrett's esophagus].
AB  - Recently, according to increasing gastroesophageal reflux disease (GERD), the
      patients with Barrett's esophagus (BE) are increasing. Since Barrett have
      reported cases of esophageal ulcers surrounding by columnar epithelium, the
      various criteria of the BE have been proposed. In 1998, practice guidelines for
      BE were developed under the auspices of the American College of Gastroenterology.
      They proposed that BE was a chance in the esophageal epithelium of any length
      that can be recognized at endoscopy, and confirmed to have intestinal metaplasia
      by biopsy of the tubular esophagus and excludes intestinal metaplasia of the
      cardia. Endoscopically, BE is determined, when 'gastric-appearing mucosa' or
      apparent 'columnar lined esophagus' is evident proximal to the esophagogastric
      junction. Histologically, BE has double muscularis mucosae, and contains a
      mixture cell types; gastric-fundic type epithelium, junctional type epithelium,
      and specialized columnar epithelium (SCE). Especially SCE is distinctive features
      of BE, available for diagnosis. On the other hand, BE is premalignant condition
      for the adenocarcinoma of the esophagus, therefore the features of the BE are
      researched to prevent and find out earlier development of adenocarcinoma. In this
      review, we referred to the definition of BE with some topics.

PMID- 16101218
TI  - [Epidemiology of Barrett's esophagus--comparison of Japan and the West].
AB  - We compared the epidemiology of Barrett's esophagus in Japan and the West. Japan
      GERD Society Study Committee conducted the epidemiological survey in 2,595
      patients who underwent endoscopy the first time, confirming that Barrett's mucosa
      was observed in 536 patients (20.8%) out of 2,577. But Barrett's esophagus (>3 cm
      of columnar lined epithelium) was detected only 5 (0.2%). The prevalence of
      typical Barrett's esophagus was markedly low in Japanese compared with
      Westerners. In Western, the incidence of Barrett's esophagus has increased
      markedly since the 1970s. It is estimated that Barrett's esophagus is found in
      approximately 6-12% of patients undergoing endoscopy for symptoms of GERD and in
      1% or less of unselected patient populations undergoing endoscopy.

PMID- 16101219
TI  - [Pathogenesis of Barrett's esophagus--new findings in the experimental studies of
      duodenal reflux models].
AB  - Duodeno-gastro-esophageal reflux has been thought to induce Barrett's esophagus.
      Recently, we designed a new duodenal reflux model using rats, and studied
      sequential morphological changes of esophageal mucosa leading to Barrett's
      esophagus. A specialized columnar epithelium (SCE) developed 20 weeks after
      operation. Barrett's epithelium originated from pyloric-foveolar metaplasia of
      stem cells in the basal layer of the esophageal squamous epithelium. The pyloric
      foveolar metaplasia was then followed by the appearance of goblet cells, becoming
      a typical SCE. The expression of homeobox gene Cdx2 was seen in this process,
      thereby suggesting a role of Cdx2 in intestinal differentiation of Barrett's
      esophagus. We noticed the pyloric-foveolar metaplasia followed by the appearance
      of goblet cells is common to entire gut in regenerative process, and proposed a
      concept of GRCL (gut regenerative cell lineage), and an implication of GRCL in
      digestive tract carcinogenesis was discussed.

PMID- 16101220
TI  - [Progression and extending speed of Barrett's esophagus].
AB  - Barrett's esophagus is one of the terminal manifestations of reflux esophagitis.
      Although the typical Barrett's esophagus is very rare in Japan, the prevalence
      rate of short-segment Barrett's esophagus is extremely higher comparing with in
      western countries. The discrepancy may be caused by the differences of criteria
      of short-segment Barrett's esophagus. Observation of Barrett's mucosa in residual
      esophagus after esophagectomy is a useful method of considering the extension of
      Barrett's esophagus. Short-segment Barrett's esophagus accompanied by gastro
      esophageal reflux may show a rapid extension under some adequate conditions.
      Large volume prospective studies are needed to clarify the extension speed of
      Barrett's esophagus.

PMID- 16101221
TI  - [Carcinogenesis of Barrett's esophagus].
AB  - Barrett's esophagus is a premalignant condition and remains the number one risk
      factor for developing adenocarcinoma. Gastro-esophageal reflux disease is a
      strong risk factor for both esophageal adenocarcinoma and the precancerous lesion
      Barrett's esophagus. Both of these conditions are related to the reflux of acid
      and bile into the esophagus. This results in inflammation and cell damage which
      initiates a sequence of events termed the metaplasia-dysplasia sequence in which
      the squamous epithelium is replaced by columnar epithelium exhibiting increasing
      degrees of dysplasia and overt malignancy. The underlying disease mechanisms
      remain unclear, but tumor suppression genes (p53, p16, APC) and, oncogenes (K
      ras, cyclin D1, c-erb-2) seem to cause the malignant transformation of Barrett's
      esophagus, and the genetic or epigenetic alterations of these genes have been
      reported.

PMID- 16101222
TI  - [Molecular events associated with Barrett's oesophagus].
AB  - The development and progression of Barrett's epithelium are accompanied with the
      acquisition of many molecular changes of the oesophageal mucosa. Gastro
      oesophageal reflux and inflammation cause the oxidative stress and free-radical
      generations, which result in the expression of oxidative-stress-related genes and
      the induction of DNA damage. The development of Barrett's epithelium follows a
      metaplasia-dysplasia-adenocarcinoma sequence, characterized by the accumulation
      of many genetic and epigenetic alterations, which are seen in carcinogenesis.
      Abnormalities in the expression of tumor suppressor genes, such as p53, p16, APC,
      and a number of molecules involved in cell proliferation, apoptosis or
      angiogenesis are observed. These genetic alterations affecting the cancer
      hallmarks provide a better understanding of the etiology and pathogenesis of the
      disease.

PMID- 16101223
TI  - [Expression of transcription factor in Barrett's esophagus].
AB  - Barrett's esophagus is the result of chronic injury which is usually caused by
      gastroesophageal reflux. NF-kappaB is expressed in the reflux esophagitis.
      Specialized columnar epithelium (SCE) is characteristic of Barrett's esophagus
      and has a malignant predisposition. SCE expresses Cdx1 and Cdx2. Adenocarcinoma
      in Barrett's esophagus is believed to develop through the metaplasia-dysplasia
      carcinoma sequence. P53, beta-catenin, PPARgamma, and estrogen receptor beta are
      closely related to the development of esophageal carcinogenesis.

PMID- 16101224
TI  - [Clinical outline of Barrett's esophagus].
AB  - Barrett's esophagus is one of the important gastrointestinal disease in Europe
      and the United States. It was recognized as not only complication of reflux
      esophagitis, but also pre-malignant lesion of adenocarcinoma. Recently,
      realization of Barrett's esophagus is attentioned in Japan, because increasing of
      reflux esophagitis for westernization of eating habit, living habit and aging of
      the population. In this section, we present general consideration and clinical
      research of Barrett's esophagus. We expect Barrett's esophagus will gradually
      increase near the future and need to research abundantly about controversial
      point of Barrett's esophagus. We also think it is important to accumulate
      intensively the clinical data of Barrett's esophagus patients.

PMID- 16101225
TI  - [Pathophysiology of Barrett's esophagus--motility disorder of esophagus].
AB  - Barrett's esophagus is a premalignant condition of reflux esophagitis and the
      prevalence is increasing in western countries. Although pathogenesis of Barrett's
      esophagus is still unknown, several studies have indicated that Barrett's
      esophagus is related to increased acid reflux through decreased lower esophageal
      sphincter tone and reduced esophageal contractions. In this article recent
      studies of Barrett's esophagus on pathophysiology of esophageal motility is
      reviewed.

PMID- 16101226
TI  - [Barrett's esophagus and Helicobacter pylori].
AB  - Lifestyles of Japanese, including eating habits, have been similar to those in
      Western countries, which might be related to an increase in gastroesophageal
      reflux disease (GERD) in Japan. Barrett's esophagus is generally accepted as a
      complication of chronic and severe GERD. Helicobacter pylori (H. pylori) is a
      pathogen that is associated with atrophic gastritis, peptic ulcer disease,
      gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and so on.
      The relationship between H. pylori and GERD+ Barrett's esophagus is
      controversial. H. pylori eradication therapy may increase the risk for the
      development of GERD, which may lead to increase a risk factor of Barrett's
      esophagus and esophageal adenocarcinoma. This review gives the outline regarding
      GERD and the relation between Barrett's esophagus and H. pylori infection.

PMID- 16101227
TI  - [A COX-2 inhibitor suppresses esophageal inflammation-metaplasia-adenocarcinoma
      sequence in rats].
AB  - A series of 90 rats underwent a duodenoesophageal reflux surgery were divided
      into 2 groups: the control group was given a commercial chow and the celecoxib
      group experimental chow containing celecoxib. The animals were sacrificed
      sequentially every 10 weeks after surgery. In the control group, esophagitis,
      columnar-lined epithelium (CLE) and adenocarcinoma (ADC) were first observed at
      the 10th, 20th, and 30th week, respectively, and their incidences sequentially
      increased and reached 100%, 89% and 47% at the 40th week, respectively. In the
      celecoxib group, the esophagitis was mild and the incidence of CLE was
      significantly lower at each week compared with the control group. ADC was not
      observed in the celecoxib group throughout the experiment. Celecoxib suppressed
      esophagitis and subsequent CLE and ADC in rats.

PMID- 16101228
TI  - [Endoscopic diagnosis of Barrett's esophagus].
AB  - In Japan Barrett's mucosa is defined as columnar lined esophagus (CLE). The
      prevalence of Barrett's esophagus and Barrett's adenocarcinoma is very low. But
      in Western countries Barrett's mucosa is defined as CLE with intestinal
      metaplasia, and many cases of Barrett's esophagus and Barrett's adenocarcinoma
      are reported. The definite endoscopic diagnosis of Barrett's mucosa cannot be so
      easy. We investigated the positional relationship between the esophageal hiatus,
      squamo-columnar junction, and longitudinal vessels in persons who underwent
      esophagogastroduodenoscopy. Subepithelial longitudinal vessels were found at the
      lower esophagus in all cases. In no cases were the longitudinal vessels observed
      under the gastric mucosa beyond the esophageal hiatus. It is peculiar to the
      esophagus to be able to observe subepithelial longitudinal vessels in the
      vicinity of the esophago-gastric junction. When longitudinal vessels are found
      only under the columnar epithelium at the oral side over the esophageal hiatus
      from the stomach, this indicates Barrett's epithelium. Thus the definite
      diagnosis of Barrett's epithelium can be made by endoscopy.

PMID- 16101229
TI  - [Diagnosis of Barrett's esophagus and Barrett's carcinoma using magnifying
      endoscopy].
AB  - Specialized columnar epithelium (SCE) in Barrett's esophagus has been detected by
      random or four quadrant biopsy using conventional endoscopy; however little is
      known about the fine mucosal structure of SCE. The fine mucosal pattern (pit
      pattern) was classified into five categories. Tubular or villous pit patterns
      were not only characteristics of both SCE and methylene blue absorption but also
      possessed intestinal mucin phenotype. Targeted biopsy under the magnifying chromo
      endoscopy might contribute to the early detection of Barrett's cancer.

PMID- 16101230
TI  - [Diagnosis of Barrett's esophagus using NBI endoscopy].
AB  - There are some problems as to chromo-endoscopy. To resolve this point, we believe
      NBI will be one of the tools supporting the endoscopic diagnosis of Barrett's
      esophagus. By only changing the optical filters for sequential lighting from the
      conventional broadband type to the narrow band type, NBI system can be installed.
      Through our clinical evaluations as to Barrett's mucosa, we confirmed NBI has an
      advantage over a conventional system with the representation of the important
      observation and diagnosis such as the capillary and the fine mucosal structure.

PMID- 16101231
TI  - [Magnification endoscopy diagnosis of Barrett's esophagus with methylene blue and
      acetic acid].
AB  - Intestinal metaplasia of Barrett's esophagus is pre-cancerous lesion and it is
      important to diagnose intestinal metaplasia by endoscopic examination. Predefined
      4 quadrant sampling technique is popular in western countries. However,
      chromoendoscopy or magnification endoscopy have been tried to diagnose intestinal
      metaplasia. We have carried out magnification endoscopy with methylene blue and
      magnification endoscopy with acetic acid. In magnification endoscopy with
      methylene blue, intestinal metaplasia showed blue-staining area with tubulaous or
      cavernous pattern. In magnification endoscopy with acetic acid, all of epithelium
      of Barrett's esophagus changed to whitening surface and it was easy to observe
      the structure of each epithelium. Intestinal metaplasia showed tubulaous or
      villous, although fundic type showed pits of small round and cardiac type showed
      oval pattern with central-slit pits.

PMID- 16101232
TI  - [Chromoendoscopic diagnosis of Barrett's esophagus].
AB  - Some kinds of chromoendoscopy have been reported to survey the cases with
      Barrett's esophagus more effectively, since random biopsy as a gold standard is
      not an ideal method from the viewpoint of safety, labor or cost effectiveness.
      Methylene blue (MB) chromoendoscopy has been reported that a targeted biopsy is
      possible to limit because MB only stains non-dysplastic Barrett's mucosa but not
      dysplastic one. However, many of supplementary studies have not agreed this
      recommendation. Crystal violet (CV) chromoendoscopy clearly stains Barrett's
      mucosa and makes a detailed observation of pit pattern possible. The availability
      of this method is required a further mass survey although CV chromoendoscopy has
      been reported to be effective in Barrett's screening. Other chromoendoscopic
      methods using indigo carmine or fluorescence dye also have been reported to be
      effective for discovering a dysplastic lesion by some investigator, but the
      efficacy has not been sufficiently evidenced. Conclusively, chromoendoscopic
      diagnosis of Barrett's esophagus has not yet got a consensus in the availability
      for Barrett's surveillance at present in Barrett's Esophagus Chicago Workshop
      2003 of AGA.

PMID- 16101233
TI  - [Histochemical diagnosis of short segment Barrett's esophagus].
AB  - Recently, we have many chances of findings of Barrett's esophagus in routine
      endoscopic examination. It is also reported that we have few frequent findings of
      typical Barrett's esophagus, long segment Barrett's esophagus (LSBE) which is
      seen predominantly in Europe and United States, however the frequency of finding
      of short segment Barrett's esophagus (SSBE) and adenocarcinoma derived from SSBE
      is gradually increasing in Japan. So it is thought that precise diagnosis of SSBE
      and the evaluation of potential malignancy of SSBE are needed in the present
      medical management. The present study has shown the differences of
      characteristics of mucinous contents and malignant potentials between in SSBE and
      LSBE by use of biopsy specimen taken by endoscopic procedure. It is well known
      that Barrett's epithelium is categorized gastric fundic type, junctional type and
      specialized columnar epithelium, especially Barrett's mucosa is characterized by
      specialized columnar epithelium, e. g. incomplete epithelial type of intestinal
      metaplasia. We have set up two characteristic groups, gastric mucin dominant and
      intestinal mucin dominant by using specific mucin staining for MUC2, MUC5AC, Con
      A and CD10. In results, we confirmed that 80% of specialized columnar epithelia
      revealed intestinal mucin dominant in LSBE and 77% revealed gastric mucin
      dominant as compared with 23%, intestinal mucin dominant. Moreover, we have
      examined the ability of cell proliferation using Ki67-immunostaining in Barrett's
      epithelia. It was demonstrated that positive immunoactivity of Ki67 in
      proliferative zone was shown in 37.5% of gastric mucin dominant and 76.5% of
      intestinal mucin dominant. The results described above suggested that specialized
      columnar epithelia with intestinal mucin dominant have a higher potential of
      malignant transformation. We concluded that the evaluation of characteristics of
      mucinous contents in specialized columnar epithelia plays an important role in
      determination of high risk group of carcinogenesis in the case of SSBE.

PMID- 16101234
TI  - [Biopsy methods and pathology of Barrett's esophagus].
AB  - We reviewed the definition of the esophagogastric junction and the biopsy sites
      and histologic findings of biopsy specimens from Barrett's esophagus. The
      borderline between the esophagus and stomach has been defined as the distal limit
      of the longitudinal vessels by the Japan Esophageal Society, because the
      longitudinal vessels are always located within the esophagus. As squamous islands
      in Barrett's mucosa are usually the orifices of esophageal glands proper, biopsy
      specimens from the squamous islands show esophageal glands proper or their ducts.
      The identification of esophageal glands proper is a definite histological
      indicator that a piece of biopsy tissue is of esophageal origin. Therefore, a
      diagnosis of Barrett's esophagus can be made purely on the basis of the
      histologic findings in these biopsy specimens of squamous islands. Since columnar
      mucosa is usually recognizable at endoscopy, a diagnosis of Barrett's esophagus
      can be made solely on the basis of endoscopic examination, without any need for
      histologic confirmation, if squamous islands are recognized in columnar-lined
      mucosa.

PMID- 16101235
TI  - [The clinical strategy for the Barrett's esophagus].
AB  - The treatment of Barrett's esophagus is controversial. Current treatments include
      endoscopic therapy, surgical procedures, gastric acid-suppressive therapy with
      proton pump inhibitors (PPIs), and cancer chemoprevention such as nonsteroidal
      anti-inflammatory drugs. Endoscopic therapy combined with gastric acid
      suppressive therapy can result in squamous reepithelialization of the Barrett's
      mucosa. Antireflux surgery and PPIs therapy are potential options for the
      treatment of gastroesophageal reflux symptoms in patients with Barrett's
      esophagus. But there are no prospective studies that support any alternative
      approach to treatment. Although chemoprevention therapy may reduce cancer risk in
      Barrett's esophagus, no randomized controlled trials that prove its efficacy have
      been reported.

PMID- 16101236
TI  - [Endoscopic therapy for Barrett's esophagus].
AB  - There are many foreign reports about the endoscopic ablation therapy for
      Barrett's esophagus. Endoscopic ablation therapy include thermal therapy
      (electrocoagulation, laser etc.), photodynamic therapy or endoscopic resection
      and so on. Ablation of Barrett's esophagus by these therapy in combination with
      adequate acid suppression lead to mucosal replacement by squamous epithelium. But
      the true value of these endoscopic therapy has not been fully investigated.
      Further studies are required.

PMID- 16101237
TI  - [The operation of Barrett's esophagus].
AB  - The purpose of operation in Barrett's esophagus is to protect against esophageal
      acid exposure. In Western countries antireflux surgery is positive because
      Barrett's esophagus is recognized as premalignancy. But in Japan many people have
      SSBE without intestinal metaplasia. Thus if cancer is not detected in Barrett's
      esophagus, it is difficult to accept surgery. Besides antireflux surgery is not
      always successful. So the extra-surgical treatment is more recommended than
      operation in Japan.

PMID- 16101238
TI  - [Medical treatment of Barrett's esophagus].
AB  - In patients with Barrett's esophagus, medical treatment is necessary for the
      control of reflux symptom, healing of accompanying erosive esophagitis, and
      prevention of carcinogenesis. For this purposes, proton pump inhibitors (PPIs)
      and aspirin/non-steroidal anti-inflammatory drugs (NSAIDs) are increasingly used.
      There are enough evidences that show the usefulness of PPIs for the control of
      reflux symptom and esophagitis. The values of PPI and aspirin/NSAIDs for the
      prevention of Barrett's carcinoma are still under investigation all over the
      world. Since many groups are actively working to find the appropriate methods for
      preventing carcinogenesis on the Barrett's esophagus, we will have an evidence
      based strategy for the prevention of Barrett's adenocarcinoma in near future.

PMID- 16101239
TI  - [Barrett's esophagus in children].
AB  - Barrett's esophagus (BE) is a condition of esophageal dysplasia in which the
      tubular esophagus is lined with columnar instead of squamous mucosa--not with
      just any type of columnar mucosa, but with a specialized type with goblet cells.
      It is considered to be an acquired phenomenon secondary to acid exposure from
      gastro-esophageal reflux (GER). This report shows a review of BE of children and
      our data about BE from the study of 19 handicapped children with GER. 3 had
      intestinal dysplasia with goblet cells (BE). The % time of pH under 4 on 24-hour
      pH monitoring was significantly lower in the patients with esophagitis including
      BE than in them with normal esophagus. BE of our study seemed to be reversible
      after the surgery and anti-acid therapy. It is suggested that BE is not a rare
      condition even in children and biopsy specimens should be taken to establish the
      diagnosis.

PMID- 16101240
TI  - [Argon plasma coagulation in Barrett's esophagus].
AB  - Argon plasma coagulation (APC) is noncontact electrocoagulation technique that
      creates tissue damage. Recently, it has been reported that Barrett's esophagus
      and Barrett's adenocarcinoma in situ could be successfully managed by APC. The
      aims of this treatment are to prevent the developing of adenocarcinoma and to
      promote the restitution of normal squamous epithelium. Combined antireflux
      surgery or proton pump inhibitor therapy are indispensable to this treatment.
      Shorter length of Barrett's epithelium and normalization in pH with PPI treatment
      were the independent predictors of sustained long-term restitution of squamous
      epithelium. In patient with Barrett's esophagus, APC offers an effective,
      minimally invasive alternative to other treatments previously performed.

PMID- 16101241
TI  - [Barrett's adenocarcinoma].
AB  - Esophageal adenocarcinoma has seen a rapid increase in incidence throughout the
      Western world. Gastroesophageal reflux disease is an important risk factor for
      this cancer that develops in patients with Barrett's esophagus, but infection
      with Helicobacter pylori may reduce the risk. The diagnosis of Barrett's
      adenocarcinoma is often at an advanced stage and is generally associated with a
      poor prognosis. Several innovative techniques (eg, chromoendoscopy, magnifying
      endoscopy, and narrow-band imaging) have recently been developed to improve the
      accuracy of diagnosis. Although surgical resection has been a mainstream
      treatment for advanced cancer, endoscopic submucosal dissection is becoming a
      promising treatment procedure for mucosal cancer. Surveillance, endoscopic
      ablative therapies, chemoprevention, and anti-reflux surgery have been developed
      for cancer prevention, but are of unproven value. Further evaluation is warranted
      to define the optimal method and standardize the procedures for diagnosis and
      management of Barrett's esophagus.

PMID- 16101242
TI  - [Present state and measures of Barrett's cancer in Japan].
AB  - Barrett's adenocarcinoma is common esophageal cancer in western countries but
      very rare in Japan. We reviewed 206 cases of Barrett's cancer in Japanese
      literature that issued from 2000 to 2004. 80% of them were superficial cancer.
      There was no mucosal Barrett's cancer with lymph nodes metastasis, therefore EMR
      (endoscopic mucosal resection) method is an appropriate way for mucosal cancer.
      Barrett's cancer with submucosal invasion occur lymph nodes metastasis, so
      surgical operation should be applied for deeper invasion to submucosal cancer.

PMID- 16101243
TI  - [Tumor suppressor gene PTEN and non-alcoholic steatohepatitis (NASH)].
AB  - Although hepatic steatosis had been considered to be a benign condition that does
      not deteriorate to either liver cirrhosis or hepatocellular carcinoma (HCC). Non
      alcoholic steatohepatitis (NASH) is notable disease that has similar pathological
      features to alcoholic liver injury and progresses to liver cirrhosis and HCC. But
      the molecular mechanism for the onset of NASH, and for the transformation from
      steatosis to carcinogenesis are still unclear. Hepatocyte-specific PTEN deficient
      mice, we generated, have similar histological features to the patients of human
      NASH. These hepatocytes showed enhanced lipid accumulation, inflammatory change,
      and hyperoxidation. Moreover, they developed into HCC. Thus, impairment of
      PI3K/PTEN signaling may possibly be involved in a part of NASH/HCC cases in
      human.

PMID- 16101244
TI  - [The metabolic syndrome and insulin resistance].
AB  - The frequency of cardiovascular disease associated with metabolic disorder is
      increasing rapidly worldwide. The metabolic syndrome, a concurrence of glucose
      intolerance, obesity, dyslipidemia, and hypertension that are risk factors for
      atherosclerosis, accounts for a large proportion of cardiovascular morbidity and
      mortality. Exceeding energy intake coupled with high fat diet, sedentary
      lifestyle, and multiple genetic factors interact to produce the metabolic
      syndrome, and insulin resistance and visceral adiposity have been suggested to be
      the common pathophysiological basis of the metabolic syndrome. Adiposity is
      correlated with altered production of so-called adipocytokines that play a role
      on the atherosclerotic angiopathy. At the cellular level, excess insulin is
      involved in VLDL-triglycerides production, decreased HDL, and various elements of
      atherogenesis. Detecting the metabolic syndrome and implementing preventive
      lifestyle interventions--diet education, physical activity, and weight control-
      is a high clinical priority.

PMID- 16101245
TI  - System failure. Most U.S. hospitals have never filed a report with the databank
      that records doctor suspensions; critics say it's time for a new method.
AB  - The National Practitioner Data Bank was born in 1990, touted as an authoritative
      way to track doctors whose privileges were suspended. Initial predictions
      expected up to 10,000 reports yearly, but only about 10,800 reports have been
      made in 15 years. Many believe hospitals skirt the system by just issuing lesser
      punishments. "It happens," admits Mark Pincus, right, the databank administrator.

PMID- 16101246
TI  - Congress mulls nurse databank.

PMID- 16101247
TI  - Healthcare's rosy outlook. S&P paints healthy financial picture for hospitals.

PMID- 16101248
TI  - Hospitals say it's not enough. Medicare payment update won't outpace inflation.

PMID- 16101249
TI  - Bonds under scrutiny. IRS audit to look at how the proceeds are used.

PMID- 16101250
TI  - The long-term problem. Solution to caring for elderly boomers must not rend the
      social safety net.

PMID- 16101251
TI  - The employer's role in quality. Companies must work harder to make pay-for
      performance work for everyone.

PMID- 16101252
TI  - Joint ventures. Hospitals seek creative solutions to grapple with the unbending
      costs of orthopedic implants.

PMID- 16101253
TI  - A profit-thinner. Hospitals, docs await substitute for risky warfarin.

PMID- 16101254
TI  - A taxing departure. Exec leaves Ill. hospital that lost state exempt status.

PMID- 16101255
TI  - Acting Governor Codey signs Health Care Professional Responsibility and Reporting
      Enhancement Act.

PMID- 16101256
TI  - Be enthusiastic about what you do!

PMID- 16101257
TI  - CRNAs take case to NJ Supreme Court.

PMID- 16101258
TI  - Survey of 76,000 nurses probes elements of job satisfaction.

PMID- 16101259
TI  - Capital Health System's Nursing--Connection Mentor Program.

PMID- 16101260
TI  - Forensic nurses join the front lines of the fight against crime.

PMID- 16101261
TI  - Evidence-based nursing care of patients suffering from Trichotillomania.

PMID- 16101262
TI  - Making electronic mail accessible: perspectives of people with acquired cognitive
      impairments, caregivers and professionals.
AB  - The primary objective of this study was to better understand the technology
      needs, barriers and strategies of individuals with acquired cognitive impairments
      (ACI) in order to design and modify technologies with potential for alleviating
      the diminished independence and social isolation common in this population. The
      authors hypothesized that (1) higher rates of computer use would be reported by
      younger, more highly educated individuals with ACI, those with less severe
      injuries and those with previous computer experience; (2) A low percentage of
      survey respondents would own their own computers; and (3) People with ACI would
      experience social isolation and report low frequency of connecting with important
      people who live far away. A total of 133 individuals with ACI, professionals and
      care providers completed the survey. To gain more specific information, seven
      focus groups were conducted with 66 individuals with ACI and 20 care providers.
      Finally, 10 current email users participated in structured conversations,
      detailing their strategies for using email. The survey revealed that 80% of
      subjects with ACI reported owning a computer. Age and education were not
      predictors of computer use, but individuals whose ACI was the result of more
      severe injuries were less likely to use computers. As expected, respondents
      reported that maintaining contact with distant loved ones is problematic. The
      focus groups and conversations provided more detail about the communication needs
      of the population and the relative advantages and disadvantages of email compared
      with telephone and mail. Participants also identified barriers to email use they
      had encountered or feared they would encounter when using email. A number of
      accommodations to overcome these barriers were suggested. The results of the
      survey, focus groups and conversations confirmed the utility of email and other
      technologies for people with ACI and the need to make these technologies more
      accessible. The results and suggestions provided by the focus groups and
      interviews are being used in the design of Think and Link, an email interface for
      use by individuals with ACI.

PMID- 16101263
TI  - Female body image following acquired brain injury.
AB  - PRIMARY OBJECTIVE: To investigate body image concerns and psycho-emotional health
      in females with acquired brain injury (ABI). RESEARCH DESIGN: Between subjects
      design. METHODS AND PROCEDURES: Thirteen females with ABI and thirteen matched
      controls were assessed on a number of variables relating to body image, self
      esteem and affect. MAIN OUTCOMES AND RESULTS: Indicated that women with ABI had a
      different profile of body image dissatisfaction than controls and that in some
      areas it was significantly worse. The women with ABI had significantly lower self
      esteem and higher levels of depression than controls and this related to body
      image. CONCLUSION: Significant changes in body image and self-concept are
      potentially damaging to quality of life post-injury and suggest a role for
      targeted therapeutic work with women with ABI.

PMID- 16101264
TI  - Psychological distress and coping in women married to men with a diagnosis of
      solvent-induced chronic toxic encephalopathy.
AB  - BACKGROUND: Solvent-induced chronic toxic encephalopathy (TE) is a slowly
      developing brain disorder associated with both a direct effect on the nervous
      system and as indirect experienced psychological distress. It can presumably also
      imply negative influence on the subject's social surroundings. METHODS: Seventeen
      women married to men diagnosed with TE (WTE) and 51 referent women of the same
      age married to healthy husbands were examined. Symptoms, social network and
      coping style were measured by questionnaires. RESULTS: The WTE reported slightly
      more psychological distress and fewer social contacts than did the referents. The
      WTE did not report affected stress management. Retired women in the WTE group
      accounted for most of the deviances from the referents. CONCLUSIONS: The
      conclusion is that becoming a WTE does not necessarily imply more psychological
      distress, social isolation or poorer stress management capability if they
      continue with their work and social activities.

PMID- 16101265
TI  - Children and young adults in a prolonged unconscious state due to severe brain
      injury: outcome after an early intensive neurorehabilitation programme.
AB  - PRIMARY OBJECTIVE: The Rehabilitation Centre Leijpark in The Netherlands provides
      an Early Intensive Neurorehabilitation Programme (EINP) to children and young
      adults in a prolonged unconscious state after severe brain injury. In an
      extensive research project the effects of EINP were studied. This part of the
      project focused on the outcome in terms of level of consciousness (LOC) in
      relation to the specific characteristics of a retrospectively studied cohort.
      RESEARCH DESIGN: This study was executed according to a one-group archived pre
      test-post-test design. SUBJECTS: Subjects were all consecutively admitted
      patients (n=145, 72% male) between December 1987-January 2001. Inclusion criteria
      were: age 0-25 years, within 6 months after injury, LOC at admission vegetative
      state (VS) or minimally conscious state (MCS). One hundred and four patients
      (72%) suffered a traumatic injury and 41 patients (28%) a non-traumatic injury.
      METHODS AND PROCEDURES: All patients had received EINP until they reached
      consciousness or until it was concluded that no progress was achieved during 3
      months after the start of EINP. Medical files were investigated to collect the
      patients' characteristics and injury data, to determine the LOC at admission and
      at discharge and to determine the discharge destination. RESULTS: Almost two
      thirds of the patients reached full consciousness. LOC at admission, aetiology
      and interval since injury were found to be significant prognostic factors.
      Traumatic patients had a much better outcome than non-traumatic patients. A
      comparison with earlier outcome studies showed a more favourable outcome than
      expected. It is argued that a multi-centre study is needed to confirm possible
      effects of EINP.

PMID- 16101266
TI  - Psychotherapy with brain injury survivors: an investigation of the challenges
      encountered by clinicians and their modifications to therapeutic practice.
AB  - OBJECTIVE: The aim of this study is to elicit practitioners' views and
      experiences of the challenges to forming a therapeutic alliance with brain injury
      survivors, with a view to informing current psychotherapeutic practice. METHODS:
      The present research utilised the data-display method, a qualitative technique,
      to examine the questionnaire responses of 21 psychologists who provide forms of
      psychotherapy for brain injury survivors at rehabilitation units in the UK. An
      anonymous postal return questionnaire was used for data collection. RESULTS: The
      main challenges to forming a working alliance comprised a range of cognitive,
      behavioural and emotional sequelae. A combination of educational, psychosocial
      and cognitive strategies were identified as being most effective in addressing
      the challenges encountered. CONCLUSIONS: A qualitative research approach has
      proved useful in identifying challenges to the formation of a working alliance
      and also the modifications to psychotherapeutic practice these challenges have
      engendered.

PMID- 16101267
TI  - Columnar organization of the mammalian visual cortex and its vulnerability
      following lesion in adult cats.
AB  - It is well known that in the mammalian visual cortex the neurons, sharing similar
      response properties, are grouped together into functional units, known as
      cortical columns. The orientation and ocular dominance columnar organization is a
      fundamental element for both the anatomical and physiological features of the
      visual cortex. Nonetheless, little is known about the functional restoration of
      matured columnar columns following injury. In the present study, the visual
      cortex of adult cats was studied electrophysiologically, whereas the primary goal
      of the study was to reveal the functional stability of the columns, disconnected
      from the main visual input. Experiments were performed on the primary visual
      cortex (area 17) of 13 anaesthetized and paralyzed adult cats. The columnar
      distortion was produced by surgical incision perpendicular to the cortical
      columns. The single unit activity was recorded from 1186 visual cells
      (experimental groups) in areas proximal and distal to the lesion and, compared to
      data, received from intact visual cortex (control group). The results indicate
      that most of the visually responsive cells were found to be selective to specific
      orientation in all experimental groups (75-100%) similar to the normal control
      group (78%). Moreover, the distribution of orientation-specific cells was very
      similar in all experimental and control groups (p > 0.05), as well as in both
      recording areas (p > 0.05). The percentage of binocular cells was significantly
      lower in all experimental groups (23-49%) in comparison to the control (80%).
      However, the distribution of the binocular cells revealed the significant
      similarity between the experimental and control groups (p > 0.05). An additional
      finding of the study is that the visual responsiveness of cells was significantly
      reduced in all experimental groups: only 28-49% of cells were found to be
      responsive following injury, as compared to 86% in normal control group (p <
      0.001). The distribution of cells has also been analysed in accordance with their
      directional specificity and it has been found that the majority of cells in the
      experimental groups were found to be bias and non-specific to light stimuli (52
      84%) as compared normal controls (21%) (p < 0.001). It has been concluded that,
      despite the fact that no improvement in visual function was found, the inherent
      structure of the disrupted cortical columns in the visual cortex was generally
      preserved. Therefore, the disruption of the columnar connection does not lead to
      remarkable distortion of the connectivity pattern on the whole, though it does
      reduce the responsiveness level there. It was concluded that the columnar
      structure for both orientation and ocular dominance is characterized by high
      stability, which enables visual processing with minimal brain connections.

PMID- 16101268
TI  - Recovery of executive skills following paediatric traumatic brain injury (TBI): a
      2 year follow-up.
AB  - PRIMARY OBJECTIVE: Disruptions to executive function (EF) may occur as a result
      of traumatic brain injury (TBI), in the context of direct damage to frontal
      regions or in association with disruption of connections between these areas and
      other brain regions. Little investigation of EF has occurred following TBI during
      childhood and there is little evidence of possible recovery trajectories in the
      years post-injury. The present study aimed to (i) examine whether a dose-response
      relationship exists between injury severity and EF; (ii) document recovery of EF
      in the 2 years post-injury and (iii) determine any additional predictors of
      outcome in the domain of EF. RESEARCH DESIGN: The study employed a prospective,
      longitudinal design, with participants recruited at time of injury and followed
      over a 2-year period. METHODS AND PROCEDURES: The study examined EF in a group of
      69 children who had sustained a mild, moderate or severe TBI. Four components of
      EF were assessed: (i) attentional control; (ii) planning, goal setting and
      problem solving; (iii) cognitive flexibility; and (iv) abstract reasoning.
      OUTCOMES AND RESULTS: Results showed that, while children with severe TBI
      performed most poorly during the acute stage post-injury, they exhibited greatest
      recovery of EF over a 24-month period. Regardless, functional deficits remained
      most severe for this group 2 years post-injury. Results demonstrated the multi
      dimensional nature of EF and the differential recovery of skills, following
      childhood TBI. Pre-injury ability and age at injury were identified as
      significant predictors of EF and functional skills. CONCLUSIONS: Children
      sustaining severe TBI at a young age are particularly vulnerable to impairments
      in EF. While these difficulties do show some recovery with time since injury,
      long-term deficits remain and may impact on ongoing development.

PMID- 16101269
TI  - Issues in perceptual speech analysis in cleft palate and related disorders: a
      review.
AB  - BACKGROUND: Perceptual speech assessment is central to the evaluation of speech
      outcomes associated with cleft palate and velopharyngeal dysfunction. However,
      the complexity of this process is perhaps sometimes underestimated. AIMS: To draw
      together the many different strands in the complex process of perceptual speech
      assessment and analysis, and make recommendations for practice. MAIN
      CONTRIBUTION: This review examines issues such as data sampling, data
      collection/recording, archiving, the advantages and disadvantages of lay and
      specialist listeners, approaches to data analysis, reliability, and data
      interpretation. CONCLUSIONS: The need to capture meaningfully the sound of speech
      based on detailed phonetic analysis is argued. Also described are some of the
      differences in measuring speech for clinical, audit and research activities.
      Blind independent analysis of speech data by specialist therapists is recommended
      as the gold standard methodological approach when reporting audit and research
      outcomes. The requirement for ongoing training in listening skills for specialist
      therapists is advocated. The limitations of an impairment-based-only approach to
      measurement are also illustrated, indicating the need to develop outcome measures
      that incorporate more functional issues that affect quality of life.

PMID- 16101270
TI  - Home environments of 10-month-old infants selected by the WILSTAAR screen for pre
      language difficulties.
AB  - BACKGROUND AND AIMS: The Ward Infant Language Screening Test, Assessment,
      Acceleration and Remediation (WILSTAAR) comprises a programme for identifying and
      helping 8-10-month-old infants showing early signs of language and communication
      difficulty. The study addresses one of the queries raised by critics of the
      programme by providing evidence about the backgrounds and home environments of
      infants who fail the WILSTAAR screening assessment. METHODS AND PROCEDURES:
      Thirty 10-month-old infants who failed the screen ('at-risk' infants) and 30
      gender- and age-matched infants who passed the screen ('not-at-risk' infants)
      were visited at home by a trained observer who collected information about the
      infants' physical and social environment and families' demographic features.
      OUTCOMES AND RESULTS: Parents of both groups were well educated, in stable
      relationships, and had no evidence of social or economic disadvantage. Measures
      of ambient sound level and television exposure did not support the hypothesis
      that the at-risk infants' environments involved high levels of noise. However,
      observations of spontaneous behaviour and a standardized Mother-Infant Play Task
      identified low amounts of social interaction in at-risk cases. During the play
      task, mothers of at-risk infants spent twice as much time without interacting
      with their infants. At-risk infants babbled one-third less than not-at-risk
      infants during 150-min observations of spontaneous behaviour. CONCLUSIONS: The
      findings point to deficiencies in social interaction and communication, involving
      both infant and parental contributions, as maintaining the infants' difficulties
      at this age. The core of the WILSTAAR intervention, of encouraging social
      communication between parents and infants, is not complex and does not need to be
      confined to at-risk cases. How this is best accomplished in the general
      community, and whether it should be included in national schemes such as Sure
      Start in the UK, are important topics for practitioners and policy-makers.

PMID- 16101271
TI  - Cognitive abilities in children with specific language impairment: consideration
      of visuo-spatial skills.
AB  - BACKGROUND: The study is concerned with the cognitive abilities of children with
      specific language impairment (SLI). Previous research has indicated that children
      with SLI demonstrate difficulties with certain cognitive tasks despite normal non
      verbal IQ scores. It has been suggested that a general processing limitation
      might account for the pattern of language and cognitive difficulties seen in
      children with SLI. The performances on a visuo-spatial short-term memory task and
      a visuo-spatial processing task were considered in a group of young children with
      SLI. Verbal short-term memory was also measured. AIMS: To identify whether
      children with SLI demonstrate difficulties with visuo-spatial memory as well as
      verbal short-term memory. To see whether a visuo-spatial processing task without
      short-term memory requirements is problematic for children with SLI. To consider
      performance on these tasks over time. METHODS AND PROCEDURES: Nine children with
      SLI (mean age 3;9 years at the study outset) and nine typically developing
      children (mean age 3;9 years at the study outset) were visited on three occasions
      over 1 year. Verbal short-term memory, visuo-spatial short-term memory and visuo
      spatial processing tasks were administered to the children, and performance over
      time was compared between the two groups. OUTCOMES AND RESULTS: The children with
      SLI performed at a lower level than the typically developing children on the
      verbal short-term memory task. Both groups showed similar development on the
      verbal short-term memory task and the visuo-spatial processing task over time.
      Only the visuo-spatial short-term memory task showed slower development over time
      in the children with SLI relative to the typically developing children.
      CONCLUSIONS: Children with SLI demonstrated slower development on a visuo-spatial
      short-term memory task relative to typically developing children of the same
      chronological age. This finding has implications for speech and language
      therapists and other professionals working with children with SLI. It may mean
      that only certain types of visual support are suitable, and that children with
      SLI will have difficulty with tasks requiring a high level of processing, or a
      number of mental manipulations.

PMID- 16101272
TI  - Comparison of the learnability and retention between Blissymbols and CyberGlyphs.
AB  - BACKGROUND: There are a variety of graphic symbol sets/systems (GSSs) currently
      used in the field of augmentative and alternative communication (AAC). Various
      characteristics of these graphic symbol systems affect learnability and should be
      considered in order to make a meaningful match between the user of AAC and the
      system. Although a variety of studies on learnability of graphic systems have
      been conducted in the past, all studies conducted included participants from
      Western countries. AIMS: To compare two symbol systems, namely Blissymbolics and
      CyberGlyphs in terms of learnability. To identify the overall performance between
      Blissymbolics and CyberGlyphs in terms of the percentage of symbols correctly
      identified at the various stages. METHODS AND PROCEDURES: A quasi-experimental
      crossover design between groups was carried out on two homogeneous groups of
      typically developing, Northern Sotho-speaking children. Data were obtained by
      teaching 80 different referents (40 from each symbol system) to 50 Northern Sotho
      speaking regular students from South Africa, ranging from grade 4 to 6. The
      participants were tested on symbol recognition at four different stages: after
      initial training, after a revision period, after a 7-day withdrawal period and
      after 30 days of withdrawal. OUTCOMES AND RESULTS: The overall results indicated
      that the ease of learning and memory retention of the CyberGlyphs were higher
      than that of Blissymbols, irrespective of the group or the sequence of exposure.
      Possible reasons for the differences are discussed. CyberGlyphs seem to be more
      accessible as the symbols in general seem to be more detailed and also are meant
      to be hand drawn rather than computer or stencil produced. Within this context,
      CyberGlyphs could be easier to access visually than Blissymbolics, especially for
      children who do not have extensive experience in dealing with geometric shapes,
      particularly for the children who do not come from rich literacy backgrounds or
      who do not have rich visual perceptual experiences to draw from. CONCLUSIONS:
      Even though initial learning might be faster for CyberGlyphs than for
      Blissymbolics in certain populations, there may be other factors to consider when
      making a choice between the two graphic symbol systems. Within the clinical
      setting CyberGlyphs can provide the individual who uses AAC with a more user
      friendly system as an entrance to the use of other graphic symbol systems. This
      may be especially important in contexts where issues surrounding poverty and lack
      of early exposure to literacy exist.

PMID- 16101273
TI  - Effects of input rate and age on the real-time language processing of children
      with specific language impairment.
AB  - BACKGROUND: School-age children with specific language impairment (SLI) exhibit
      slower real-time (i.e. immediate) language processing relative to same-age peers.
      The offline sentence comprehension of children with SLI can be improved when the
      input is slowed down. Although this finding suggests that a slower input delivery
      facilitates these children's language processing, such an interpretation is
      premature, as there are no data directly addressing the issue. Additionally,
      while typically developing (TD) children demonstrate age-related improvements in
      language processing (i.e. they become faster processors), it is unclear whether
      children with SLI show the same developmental improvement. AIMS: It was
      investigated whether a reduced input rate can enhance the online language
      processing of children with SLI. If it does, their reaction time (RT) for
      recognizing words embedded in sentences delivered at a slow rate should be faster
      relative to words in normal- and fast-rate sentences. For TD children, RT should
      be unaffected by rate manipulation, as their language-processing system is
      sufficiently robust to handle such a simple input manipulation. A secondary aim
      was to provide preliminary data on the developmental course of language
      processing proficiency in children with SLI. METHODS AND PROCEDURES: Twenty
      school-age children with SLI and 20 age-matched TD children completed a word
      recognition RT task. Children monitored simple sentences for a target word and
      made a timed response immediately upon recognizing the target. Sentences were
      presented at 'normal', 'slow' and 'fast' speaking rates. OUTCOMES AND RESULTS:
      There was a significant group by input rate interaction. Children with SLI,
      relative to TD peers, yielded significantly slower RT for normal- and fast-rate
      sentences, but faster RT for slow-rate sentences. Within-group analyses showed
      the children with SLI produced the fastest RT for slow-rate sentences and the
      slowest RT for fast-rate sentences. The TD children showed the opposite response
      pattern: the fastest RT for fast-rate sentences and the slowest RT for slow-rate
      sentences. Age also had a significant effect. Regardless of language status,
      older children produced faster RT than younger children. Interestingly, even the
      oldest children with SLI still demonstrated significantly slower RT than the
      youngest TD children. CONCLUSIONS: The real-time language processing of children
      with SLI can be facilitated when the material is presented at a slower rate. A
      slower rate apparently allows these children time to allocate their attentional
      resources more effectively to the various processing operations supporting
      comprehension. Additionally, the language proficiency of children with SLI
      improves with age. However, older children with SLI are still slower than their
      youngest TD peers, suggesting that the language-processing apparatus of children
      with SLI operates even more inefficiently than what their receptive language
      knowledge might otherwise predict.

PMID- 16101274
TI  - Phonological therapy within a psycholinguistic framework: promoting change in a
      child with persisting speech difficulties.
AB  - BACKGROUND: Single case studies are a valuable means of providing information
      about the outcomes of speech and language intervention. Many previous studies
      have used phonological analysis as a theoretical basis, while others have used
      psycholinguistic models. The present study combines these approaches to
      assessment, intervention and evaluation of outcomes. AIMS: The aim of the
      research was to determine if intensive psycholinguistically based intervention
      could result in (a) specific and (b) generalized improvements in the speech
      production of a child with severe and persisting phonological difficulties.
      METHODS AND PROCEDURES: A single subject research design was used with pre- and
      post-intervention assessment carried out. Assessment took place at two levels:
      the macro level focused on global change in the child's speech processing system
      using psycholinguistic speech profiling and phonological analyses; the micro
      assessment focused on specific, treated (and matched control) stimuli. There were
      three phases of intervention with a total of 30 hours of therapy. OUTCOMES AND
      RESULTS: Micro evaluation showed significant changes in Katy's single word and
      connected speech production--as well as in other areas such as spelling and
      auditory discrimination of closely related real word pairs. Macro evaluation
      revealed significant improvement in speech severity indices (PCC, PPC), and gains
      in her ability to discriminate between closely related real word pairs. These
      changes were maintained at follow-up seven months after intervention had ceased.
      CONCLUSIONS: Specific and intensive intervention brought about significant
      improvements in this child's speech, spelling and auditory discrimination at the
      micro level, and in speech and auditory discrimination at a macro level. The
      macro level assessments reveal persisting core deficits requiring further focused
      intervention before changes can be observed more widely. When carefully defined
      and evaluated, speech and language intervention can have positive outcomes for
      children with severe and persisting speech difficulties.

PMID- 16101275
TI  - 'Thinking for two': a case study of speech and language therapists working
      through assistants.
AB  - BACKGROUND: Many speech and language therapists (SLTs) in the UK work with speech
      and language therapy assistants, and the numbers of SLT assistants is expected to
      grow. There has been very little empirical investigation of how SLTs feel about
      this situation or the effect on working practices of working indirectly. AIMS: To
      investigate SLTs' opinions on working with SLT assistants in a small-scale
      research case study. METHODS AND PROCEDURES: The study design was a case study of
      five SLTs delivering intervention within a research intervention project.
      Prepared questionnaire and formal interview techniques were used to elicit
      opinions on working through assistants, and a content analysis was performed.
      OUTCOMES AND RESULTS: Although respondents could see value in working through
      assistants, they stressed the time required to do so and the difficulties of
      adapting and updating therapy plans when working indirectly. CONCLUSIONS: The
      study suggests a variety of factors that have to be carefully managed if SLTs are
      to work competently through assistants.

PMID- 16101276
TI  - Structural characterization of a complex of photosystem I and light-harvesting
      complex II of Arabidopsis thaliana.
AB  - Chloroplasts are central to the provision of energy for green plants. Their
      photosynthetic membrane consists of two major complexes converting sunlight:
      photosystem I (PSI) and photosystem II (PSII). The energy flow toward both
      photosystems is regulated by light-harvesting complex II (LHCII), which after
      phosphorylation can move from PSII to PSI in the so-called state 1 to state 2
      transition and can move back to PSII after dephosphorylation. To investigate the
      changes of PSI and PSII during state transitions, we studied the structures and
      frequencies of all major membrane complexes from Arabidopsis thaliana
      chloroplasts at conditions favoring either state 1 or state 2. We solubilized
      thylakoid membranes with digitonin and analyzed the complete set of complexes
      immediately after solubilization by electron microscopy and image analysis.
      Classification indicated the presence of a PSI-LHCII supercomplex consisting of
      one PSI-LHCI complex and one LHCII trimer, which was more abundant in state 2
      conditions. The presence of LHCII was confirmed by excitation spectra of the PSI
      emission of membranes in state 1 or state 2. The PSI-LHCII complex could be
      averaged with a resolution of 16 A, showing that LHCII has a specific binding
      site at the PSI-A, -H, -L, and -K subunits.

PMID- 16101277
TI  - Structural basis for cell cycle checkpoint control by the BRCA1-CtIP complex.
AB  - The breast and ovarian tumor suppressor BRCA1 has important functions in cell
      cycle checkpoint control and DNA repair. Two tandem BRCA1 C-terminal (BRCT)
      domains are essential for the tumor suppression activity of BRCA1 and interact in
      a phosphorylation-dependent manner with proteins involved in DNA damage-induced
      checkpoint control, including the DNA helicase BACH1 and the CtBP-interacting
      protein (CtIP). The crystal structure of the BRCA1 BRCT repeats bound to the
      PTRVSpSPVFGAT phosphopeptide corresponding to residues 322-333 of human CtIP was
      determined at 2.5 A resolution. The peptide binds to a cleft formed by the
      interface of the two BRCTs in a two-pronged manner, with phospho-Ser327 and
      Phe330 anchoring the peptide through extensive contacts with BRCA1 residues.
      Several hydrogen bonds and salt bridges that stabilize the BRCA1-BACH1 complex
      are missing in the BRCA1-CtIP interaction, offering a structural basis for the
      approximately 5-fold lower affinity of BRCA1 for CtIP compared to that of BACH1,
      as determined by isothermal titration calorimetry. Importantly, the side chain of
      Arg1775 in the cancer-associated BRCA1 mutation M1775R sterically clashes with
      the phenyl ring of CtIP Phe330, disrupting the BRCA1-CtIP interaction. These
      results provide new insights into the molecular mechanisms underlying the dynamic
      selection of target proteins involved in DNA repair and cell cycle control by
      BRCA1 and reveal how certain cancer-associated mutations affect these
      interactions.

PMID- 16101278
TI  - Crystal structure of the ephrin-B1 ectodomain: implications for receptor
      recognition and signaling.
AB  - Eph receptors and their ephrin ligands are involved in various aspects of cell
      cell communication during development, including axonal pathfinding in the
      nervous system and cell-cell interactions of the vascular endothelial cells.
      Recent structural studies revealed unique molecular features, not previously seen
      in any other receptor-ligand families, and explained many of the biochemical and
      signaling properties of Ephs and ephrins. However, unresolved questions remain
      regarding the potential oligomerization and clustering of these important
      signaling molecules. In this study, the biophysical properties and receptor
      binding preferences of the extracellular domain of ephrin-B1 were investigated
      and its crystal structure was determined at 2.65 A resolution. Ephrin-B1 is a
      monomer both in solution and in the crystals, while it was previously shown that
      the closely related ephrin-B2 forms homodimers. The main structural difference
      between ephrin-B1 and ephrin-B2 is the conformation of the receptor-binding G-H
      loop and the partially disordered N-terminal tetramerization region of ephrin-B1.
      The G-H loop is structurally rigid in ephrin-B2 and adopts the same conformation
      in both the receptor-bound and unbound ligand, where it mediates receptor
      independent homodimerization. In the ephrin-B1 structure, on the other hand, the
      G-H loop is not involved in any homotypic interactions and adopts a new, distinct
      conformation. The implications of the ephrin-B1 structure, in context of
      available ephrin-B1 mutagenesis data, for the mechanism of Eph-ephrin recognition
      and signaling initiation are discussed.

PMID- 16101279
TI  - Characterization and structural analysis of an active particulate methane
      monooxygenase trimer from Methylococcus capsulatus (Bath).
AB  - The oxidation of methane to methanol in methanotrophs is catalyzed by the enzyme
      methane monooxygenase (MMO). Two distinct forms of this enzyme exist, a soluble
      cytoplasmic MMO (sMMO) and a membrane-bound particulate form (pMMO). We describe
      here the biochemical characterization of a stable and active purified pMMO
      hydroxylase (pMMO-H) and report a three-dimensional (3D) structure, determined by
      electron microscopy and single-particle analysis at 23 A resolution. Both
      biochemical and structural data indicate that pMMO hydroxylase is trimeric, with
      each monomer unit comprised of three polypeptides of 47, 26, and 23 kDa.
      Comparison of the recent crystal structure [Lieberman, R. L., and Rosenzweig, A.
      C. (2005) Nature 434, 177] of an uncharacterized pMMO-H complex with the three
      dimensional (3D) structure determined here yielded a good match between the
      principal features and the organization of the enzyme monomers into trimers. The
      data presented here advance our current understanding of particulate methane
      monooxygenase function by the characterization of an active form of the enzyme
      and the corresponding 3D structure.

PMID- 16101280
TI  - Crystal structure of the D94S/G98E variant of rat alpha-parvalbumin. An
      explanation for the reduced divalent ion affinity.
AB  - Simultaneous replacement of Asp-94 with serine and Gly-98 with glutamate in rat
      alpha-parvalbumin creates a CD-site ligand array in the context of the EF-site
      binding loop. Previous work has shown that, relative to the wild-type CD site,
      this engineered site has markedly reduced Ca(2+) affinity. Seeking an explanation
      for this phenomenon, we have obtained the crystal structure of the alpha
      D94S/G98E variant. The Ca(2+) coordination within the engineered EF site of the
      94/98E variant is nearly identical to that within the CD site, suggesting that
      the attenuated affinity of the EF site in 94/98E is not a consequence of
      suboptimal coordination geometry. We have also examined the divalent ion binding
      properties of the alpha 94/98E variant in both Na(+)- and K(+)-containing
      buffers. Although the Ca(2+) and Mg(2+) affinities are higher in K(+) solution,
      the increases are comparable to those observed for wild-type alpha. Consistent
      with that finding, the apparent Na(+) stoichiometry, estimated from stability
      studies conducted as a function of Na(+) concentration, is 1.0 +/- 0.1, identical
      to that of wild-type alpha. Thus, the reduced affinity for divalent ions is
      evidently not the result of heightened monovalent ion competition. The
      thermodynamic analysis indicates that the less favorable Gibbs free energy of
      binding reflects a substantial enthalpic penalty. Significantly, the crystal
      structure reveals a steric clash between Phe-57 and the C(gamma) atom of Glu-98.
      The consequent displacement of Phe-57 also produces a close contact with Ser-55.
      Thus, steric interference may be the source of the enthalpic penalty.

PMID- 16101281
TI  - Structural analysis of the SH3 domain of beta-PIX and its interaction with alpha
      p21 activated kinase (PAK).
AB  - The PAK Ser/Thr kinases are important downstream effectors of the Rho family
      GTPases Cdc42 and Rac, partly mediating the role of these G proteins in cell
      proliferation and cytoskeletal rearrangements. As well as small G proteins, PAK
      interacts with the Cdc42/Rac exchange factor beta-PIX via the PIX SH3 domain and
      a nontypical Pro-rich region in PAK. This interaction is thought to affect the
      localization of PAK, as well as increased GTP/GDP exchange of Rac and Cdc42. We
      have determined the structure of the PIX-SH3/PAK peptide complex and shown that
      it differs from typical Src-like SH3/peptide complexes. The peptide makes
      contacts through the Pro-rich sequence in a similar way to standard SH3/peptide
      complexes, even though the Pro residue positions are not conserved. In addition,
      there are interactions with a Pro and Lys in the PAK, which are C-terminal to the
      conserved Arg found in all SH3-binding sequences. These contact a fourth binding
      pocket on the SH3 domain. We have measured the affinity of PIX-SH3 for the PAK
      peptide and found that it is of intermediate affinity. When PAK is activated, Ser
      199 in the PIX-binding site is phosphorylated. This phosphorylation is sufficient
      to reduce the affinity for PIX 6-fold.

PMID- 16101282
TI  - Oligomerization-induced differential dephosphorylation of c-Met receptor tyrosine
      kinase.
AB  - Although protein tyrosine phosphatases (PTPs) are significant negative regulators
      of receptor tyrosine kinase (RTK)-initiated cell signaling, it is unknown how RTK
      oligomerization modulates the equilibrium established between kinase and
      phosphatase activity. To determine the impact of oligomerization on the ability
      of c-MET RTK to undergo dephosphorylation, we examined the relative
      dephosphorylation kinetics of similarly phosphorylated dimeric TPR-MET and
      monomeric cytoMET. Notably, we observed that the dephosphorylation kinetics of
      phosphorylated MET were significantly modulated by its oligomeric state, with the
      global dephosphorylation rate of TPR-MET severalfold slower than the
      dephosphorylation rate of monomeric cytoMET. Furthermore, there were important
      site-specific differences in the dephosphorylation patterns of cytoMET and TPR
      MET. Reduced dephosphorylation activity was predicted to eliminate or reduce the
      requirement of ligand-dependent oligomerization for MET autophosphorylation. This
      was demonstrated by the rapid phosphorylation of unstimulated c-MET on its
      activation loop and carboxy-terminal tyrosines following pervanadate treatment of
      cells expressing c-MET. We conclude that the MET oligomerization state is a
      critical regulator of its dephosphorylation rate. Thus, oligomerization plays a
      role in modifying the receptor's kinase and dephosphorylation rates to change the
      equilibrium levels of phosphorylated and dephosphorylated receptor in response to
      ligand stimulation, and that this may be a general mechanism utilized by many
      oligomeric receptor tyrosine kinases for regulation of their activity.

PMID- 16101283
TI  - Modeling binding kinetics at the Q(A) site in bacterial reaction centers.
AB  - Bacterial reaction centers (RCs) catalyze a series of electron-transfer reactions
      reducing a neutral quinone to a bound, anionic semiquinone. The dissociation
      constants and association rates of 13 tailless neutral and anionic benzo- and
      naphthoquinones for the Q(A) site were measured and compared. The K(d) values for
      these quinones range from 0.08 to 90 microM. For the eight neutral quinones,
      including duroquinone (DQ) and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UQ(0)),
      the quinone concentration and solvent viscosity dependence of the association
      rate indicate a second-order rate-determining step. The association rate
      constants (k(on)) range from 10(5) to 10(7) M(-)(1) s(-)(1). Association and
      dissociation rate constants were determined at pH values above the hydroxyl pK(a)
      for five hydroxyl naphthoquinones. These negatively charged compounds are
      competitive inhibitors for the Q(A) site. While the neutral quinones reach
      equilibrium in milliseconds, anionic hydroxyl quinones with similar K(d) values
      take minutes to bind or dissociate. These slow rates are independent of ionic
      strength, solvent viscosity, and quinone concentration, indicating a first-order
      rate-limiting step. The anionic semiquinone, formed by forward electron transfer
      at the Q(A) site, also dissociates slowly. It is not possible to measure the
      association rate of the unstable semiquinone. However, as the protein creates
      kinetic barriers for binding and releasing anionic hydroxyl quinones without
      greatly increasing the affinity relative to neutral quinones, it is suggested
      that the Q(A) site may do the same for anionic semiquinone. Thus, the slow
      semiquinone dissociation may not indicate significant thermodynamic stabilization
      of the reduced species in the Q(A) site.

PMID- 16101284
TI  - Protonation of the binuclear metal center within the active site of
      phosphotriesterase.
AB  - Phosphotriesterase (PTE) is a binuclear metalloenzyme that catalyzes the
      hydrolysis of organophosphates, including pesticides and chemical warfare agents,
      at rates approaching the diffusion controlled limit. The catalytic mechanism of
      this enzyme features a bridging solvent molecule that is proposed to initiate
      nucleophilic attack at the phosphorus center of the substrate. X-band EPR
      spectroscopy is utilized to investigate the active site of Mn/Mn-substituted PTE.
      Simulation of the dominant EPR spectrum from the coupled binuclear center of
      Mn/Mn-PTE requires slightly rhombic zero-field splitting parameters. Assuming
      that the signal arises from the S = 2 manifold, an exchange coupling constant of
      J = -2.7 +/- 0.2 cm(-)(1) (H(ex) = -2JS(1) x S(2)) is calculated. A kinetic pK(a)
      of 7.1 +/- 0.1 associated with loss in activity at low pH indicates that a
      protonation event is responsible for inhibition of catalysis. Analysis of changes
      in the EPR spectrum as a function of pH provides a pK(a) of 7.3 +/- 0.1 that is
      assigned as the protonation of the hydroxyl bridge. From the comparison of
      kinetic and spectral pK(a) values, it is concluded that the loss of catalytic
      activity at acidic pH results from the protonation of the hydroxide that bridges
      the binuclear metal center.

PMID- 16101285
TI  - Metal binding sites in proteins: identification and characterization by
      paramagnetic NMR relaxation.
AB  - A method is presented that allows the identification and quantitative
      characterization of metal binding sites in proteins using paramagnetic nuclear
      magnetic resonance spectroscopy. The method relies on the nonselective
      longitudinal relaxation rates of the amide protons and their dependence on the
      paramagnetic metal ion concentration and the pH, and on the three-dimensional
      structure of the protein. The method is demonstrated using Escherichia coli
      thioredoxin as a model protein and Ni(2+) as the paramagnetic metal ion. Through
      a least-squares analysis of the relaxation rates, it is found that Ni(2+) binds
      to a series of specific sites on the surface of thioredoxin. The strongest
      binding site is found near the N-terminus of the protein, where the metal ion is
      coordinated to the free NH(2) group of the N-terminal serine residue and the side
      chain carboxylate group of the aspartic acid residue in position 2. In addition,
      Ni(2+) binds specifically but more weakly to the surface-exposed side chain
      carboxylate groups of residues D10, D20, D47, and E85.

PMID- 16101286
TI  - Roles of the equatorial tyrosyl iron ligand of protocatechuate 3,4-dioxygenase in
      catalysis.
AB  - The active site Fe(III) of protocatechuate 3,4-dioxygenase (3,4-PCD) from
      Pseudomonas putida is ligated axially by Tyr447 and His462 and equatorially by
      Tyr408, His460, and OH(-). Tyr447 and OH(-) are displaced as protocatechuate (3,4
      dihydroxybenzoate, PCA) chelates the iron and appear to serve as in situ bases to
      promote this process. The role(s) of Tyr408 is (are) explored here using mutant
      enzymes that exhibit less than 0.1% wild-type activity. The X-ray crystal
      structures of the mutants and their PCA complexes show that the new shorter
      residues in the 408 position cannot ligate the iron and instead interact with the
      iron through solvents. Moreover, PCA binds as a monodentate rather than a
      bidentate ligand, and Tyr447 fails to dissociate. Although the new residues at
      position 408 do not directly bind to the iron, large changes in the spectroscopic
      and catalytic properties are noted among the mutant enzymes. Resonance Raman
      features show that the Fe-O bond of the monodentate 4-hydroxybenzoate (4HB)
      inhibitor complex is significantly stronger in the mutants than in wild-type 3,4
      PCD. Transient kinetic studies show that PCA and 4HB bind to 3,4-PCD in a fast,
      reversible step followed by a step in which coordination to the metal occurs; the
      latter process is at least 50-fold slower in the mutant enzymes. It is proposed
      that, in wild-type 3,4-PCD, the Lewis base strength of Tyr408 lowers the Lewis
      acidity of the iron to foster the rapid exchange of anionic ligands during the
      catalytic cycle. Accordingly, the increase in Lewis acidity of the iron caused by
      substitution of this residue by solvent tends to make the iron substitution
      inert. Tyr447 cannot be released to allow formation of the usual dianionic PCA
      chelate complex with the active site iron, and the rate of electrophilic attack
      by O(2) becomes rate limiting overall. The structures of the PCA complexes of
      these mutant enzymes show that hydrogen-bonding interactions between the new
      solvent ligand and the new second-sphere residue in position 408 allow this
      residue to significantly influence the spectroscopic and kinetic properties of
      the enzymes.

PMID- 16101287
TI  - Temperature-induced conformational change at the catalytic site of Sulfolobus
      solfataricus alcohol dehydrogenase highlighted by Asn249Tyr substitution. A
      hydrogen/deuterium exchange, kinetic, and fluorescence quenching study.
AB  - A combination of hydrogen/deuterium exchange, fluorescence quenching, and kinetic
      studies was used to acquire experimental evidence for the crystallographically
      hypothesized increase in local flexibility which occurs in thermophilic NAD(+)
      dependent Sulfolobus solfataricus alcohol dehydrogenase (SsADH) upon substitution
      Asn249Tyr. The substitution, located at the adenine-binding site, proved to
      decrease the affinity for both coenzyme and substrate, rendering the mutant
      enzyme 6-fold more active when compared to the wild-type enzyme [Esposito et al.
      (2003) FEBS Lett. 539, 14-18]. The amide H/D exchange data show that the wild
      type and mutant enzymes have similar global flexibility at 22 and 60 degrees C.
      However, the temperature dependence of the Stern-Volmer constant determined by
      acrylamide quenching shows that the increase in temperature affects the local
      flexibility differently, since the K(SV) increment is significantly higher for
      the wild-type than for the mutant enzyme over the range 18-45 degrees C.
      Interestingly, the corresponding van't Hoff plot (log K(SV) vs 1/T) proves
      nonlinear for the apo and holo wild-type and apo mutant enzymes, with a break at
      approximately 45 degrees C in all three cases due to a conformational change
      affecting the tryptophan microenvironment experienced by the quencher molecules.
      The Arrhenius and van't Hoff plots derived from the k(cat) and K(M)
      thermodependence measured with cyclohexanol and NAD(+) at different temperatures
      display an abrupt change of slope at 45-50 degrees C. This proves more pronounced
      in the case of the mutant enzyme compared to the wild-type enzyme due to a
      conformational change in the structure rather than to an overlapping of two or
      more rate-limiting reaction steps with different temperature dependencies of
      their rate constants. Three-dimensional analysis indicates that the observed
      conformational change induced by temperature is associated with the flexible
      loops directly involved in the substrate and coenzyme binding.

PMID- 16101288
TI  - Mutational analysis of a nucleosidase involved in quorum-sensing autoinducer-2
      biosynthesis.
AB  - 5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) is important in
      a number of cellular functions such as polyamine biosynthesis, methionine
      salvaging, biological methylation, and quorum sensing. The nucleosidase is found
      in many microbes but not in mammalian systems, thus making MTAN a broad-spectrum
      antimicrobial drug target. Substrate binding and catalytic residues were
      identified from the crystal structure of MTAN complexed with 5'
      methylthiotubercidin [Lee, J. E., Cornell, K. A., Riscoe, M. K. and Howell, P. L.
      (2003) J. Biol. Chem. 278 (10) 8761-8770]. The roles of active site residues
      Met9, Glu12, Ile50, Ser76, Val102, Phe105, Tyr107, Phe151, Met173, Glu174,
      Arg193, Ser196, Asp197, and Phe207 have been investigated by site-directed
      mutagenesis and steady-state kinetics. Mutagenesis of residues Glu12, Glu174, and
      Asp197 completely abolished activity. The location of Asp197 and Glu12 in the
      active site is consistent with their having a direct role in enzyme catalysis.
      Glu174 is suggested to be involved in catalysis by stabilizing the transition
      state positive charge at the O3', C2', and C3' atoms and by polarizing the 3'
      hydroxyl to aid in the flow of electrons to the electron withdrawing purine base.
      This represents the first indication of the importance of the 3'-hydroxyl in the
      stabilization of the transition state. Furthermore, mutation of Arg193 to alanine
      shows that the nucleophilic water is able to direct its attack without assistance
      from the enzyme. This mutagenesis study has allowed a reevaluation of the
      catalytic mechanism.

PMID- 16101289
TI  - Crystal structure of the disintegrin heterodimer from saw-scaled viper (Echis
      carinatus) at 1.9 A resolution.
AB  - Disintegrins constitute a family of potent polypeptide inhibitors of integrins.
      Integrins are transmembrane heterodimeric molecules involved in cell-cell and
      cell-extracellular matrix interactions. They are involved in many diseases such
      as cancer and thrombosis. Thus, disintegrins have a great potential as anticancer
      and antithrombotic agents. A novel heterodimeric disintegrin was isolated from
      the venom of saw-scaled viper (Echis carinatus) and was crystallized. The
      crystals diffracted to 1.9 A resolution and belonged to space group P4(3)2(1)2.
      The data indicated the presence of a pseudosymmetry. The structure was solved by
      applying origin shifts to the disintegrin homodimer schistatin solved in space
      group I4(1)22 with similar cell dimensions. The structure refined to the final
      R(cryst)/R(free) factors of 0.213/0.253. The notable differences are observed
      between the loops, (Gln39-Asp48) containing the important Arg42-Gly43-Asp44, of
      the present heterodimer and schistatin. These differences are presumably due to
      the presence of two glycines at positions 43 and 46 that allow the molecule to
      adopt variable conformations. A comparative analysis of the surface-charge
      distributions of various disintegrins showed that the charge distribution on
      monomeric disintegrins occurred uniformly over the whole surface of the molecule,
      while in the dimeric disintegrins, the charge is distributed only on one face.
      Such a feature may be important in the binding of two integrins to a single
      dimeric disintegrin. The phylogenetic analysis developed on the basis of amino
      acid sequence and three-dimensional structures indicates that the protein
      diversification and evolution presumably took place from the medium disintegrins
      and both the dimeric and short disintegrins evolved from them.

PMID- 16101290
TI  - Allosteric activation of protein phosphatase 2C by D-chiro-inositol
      galactosamine, a putative mediator mimetic of insulin action.
AB  - Insulin-stimulated glucose disposal in skeletal muscle proceeds predominantly
      through a nonoxidative pathway with glycogen synthase as a rate-limiting enzyme,
      yet the mechanisms for insulin activation of glycogen synthase are not understood
      despite years of investigation. Isolation of putative insulin second messengers
      from beef liver yielded a pseudo-disaccharide consisting of pinitol (3-O-methyl-d
      chiro-inositol) beta-1,4 linked to galactosamine chelated with Mn(2+) (called
      INS2). Here we show that chemically synthesized INS2 has biological activity that
      significantly enhances insulin reduction of hyperglycemia in streptozotocin
      diabetic rats. We used computer modeling to dock INS2 onto the known three
      dimensional crystal structure of protein phosphatase 2C (PP2C). Modeling and
      FlexX/CScore energy minimization predicted a unique favorable site on PP2C for
      INS2 in a surface cleft adjacent to the catalytic center. Binding of INS2 is
      predicted to involve formation of multiple H-bonds, including one with residue
      Asp163. Wild-type PP2C activity assayed with a phosphopeptide substrate was
      potently stimulated in a dose-dependent manner by INS2. In contrast, the D163A
      mutant of PP2C was not activated by INS2. The D163A mutant and wild-type PP2C in
      the absence of INS2 had the same Mn(2+)-dependent phosphatase activity with p
      nitrophenyl phosphate as a substrate, showing that this mutation did not disrupt
      the catalytic site. We propose that INS2 allosterically activates PP2C,
      fulfilling the role of a putative mediator mimetic of insulin signaling to
      promote protein dephosphorylation and metabolic responses.

PMID- 16101291
TI  - Single-molecule characterization of the dynamics of calmodulin bound to
      oxidatively modified plasma-membrane Ca2+-ATPase.
AB  - We used single-molecule fluorescence spectroscopy to probe the conformation of
      calmodulin (CaM) bound to oxidatively modified plasma-membrane Ca(2+)-ATPase
      (PMCAox). We found that oxidative modification altered the coupling between the
      ATP binding domain and the autoinhibitory domain. Oxidative modification of PMCA
      is known to result in a loss of activity for the enzyme. Conformations of PMCAox
      CaM complexes were probed by single-molecule polarization modulation
      spectroscopy, which measured the orientational mobility of fluorescently labeled
      CaM bound to PMCAox. We detected an enhanced population of PMCAox-CaM complexes
      with a low orientational mobility in the presence of ATP, whereas nonoxidized
      PMCA-CaM complexes existed almost exclusively in a high-mobility state in the
      presence of ATP. We have previously attributed such high-mobility states to PMCA
      CaM complexes with a dissociated autoinhibitory/CaM binding domain, whereas the
      lower-mobility state was attributed to autoinhibited PMCA-CaM complexes with a
      nondissociated autoinhibitory domain [Osborn, K. D., et al. (2004) Biophys. J.
      87, 1892-1899]. In the absence of ATP, the orientational mobility distributions
      are similar for CaM complexed with oxidized PMCA or nonoxidized PMCA. These
      results suggest that oxidative modification of PMCA reduced the propensity of the
      autoinhibitory domain to dissociate from binding sites near the catalytic core of
      the enzyme with bound nucleotide upon CaM stimulation in the presence of Ca(2+).
      This interpretation was further supported by chymotrypsin proteolysis, which
      probes the tightness of binding of the autoinhibitory domain to sites near the
      catalytic core of the enzyme. Enhanced proteolysis was observed for PMCA upon
      binding CaM or ATP. In contrast, proteolysis was partially blocked for
      oxidatively modified PMCA, even in the presence of ATP.

PMID- 16101292
TI  - Production of calcium-mobilizing metabolites by a novel member of the ADP-ribosyl
      cyclase family expressed in Schistosoma mansoni.
AB  - ADP-ribosyl cyclases are structurally conserved enzymes that are best known for
      catalyzing the production of the calcium-mobilizing metabolite, cyclic adenosine
      diphosphate ribose (cADPR), from nicotinamide adenine dinucleotide (NAD(+)).
      However, these enzymes also produce adenosine diphosphate ribose (ADPR) and
      nicotinic acid adenine dinucleotide phosphate (NAADP(+)), both of which have been
      shown to modulate calcium mobilization in vitro. We have now characterized a new
      member of the cyclase family from Schistosoma mansoni, a member of the
      Platyhelminthes phylum. We show that the novel NAD(P)(+) catabolizing enzyme
      (NACE) expressed by schistosomes is structurally most closely related to the
      cyclases cloned from Aplysia but also shows significant homology with the
      mammalian cyclases, CD38 and CD157. NACE expression is developmentally regulated
      in schistosomes, and the GPI-anchored protein is localized to the outer tegument
      of the adult schistosome. Importantly, NACE, like all members of the cyclase
      family, is a multifunctional enzyme and catalyzes NAD(+) glycohydrolase and base
      exchange reactions to produce ADPR and NAADP(+). However, despite being competent
      to generate a cyclic product from NGD(+), a nonphysiologic surrogate substrate,
      NACE is so far the only enzyme in the cyclase family that is unable to produce
      significant amounts of cADPR (<0.02% of reaction products) using NAD(+) as the
      substrate. This suggests that the other calcium-mobilizing metabolites produced
      by NACE may be more important for calcium signaling in schistosomes.
      Alternatively, the function of NACE may be to catabolize extracellular NAD(+) to
      prevent its use by host enzymes that utilize this source of NAD(+) to facilitate
      immune responses.

PMID- 16101293
TI  - The KLF2 transcription factor does not affect the formation of preadipocytes but
      inhibits their differentiation into adipocytes.
AB  - Kruppel-like transcription factor 2 (KLF2), a critical gene for mouse
      embryogenesis, was recently identified as an inhibitor of adipogenesis. However,
      it is still unknown whether KLF2 is a natural repressor of adipocyte
      differentiation and if KLF2 affects the formation of preadipocytes. It may also
      be important for preadipocyte formation, as KLF2 is crucial for lung development
      and blood vessel formation. In this study, we show that differentiation of
      preadipocytes not only results in a concomitant decrease in the levels of KLF2
      protein but also significantly reduces KLF2 promoter activity. We have generated
      tet-responsive lines of 3T3L1 that express physiological levels of KLF2 and show
      that reexpression of KLF2 prevents preadipocyte differentiation, thereby
      confirming the inhibition of adipogenesis by KLF2, partially via the restoration
      of Pref-1. In addition, we studied the contribution of KLF2-negative cells to the
      formation and subsequent differentiation of preadipocytes. We demonstrate that
      embryoid bodies derived from KLF2(-)(/)(-) ES cells can differentiate into
      adipocytes as evidenced by the accumulation of lipids and expression of several
      biochemical markers. Moreover, mouse embryonic fibroblasts (MEFs) derived from
      KLF2(-)(/)(-) mouse embryos differentiate efficiently into adipocytes.
      Interestingly, quantification of lipid accumulation in MEFs indicated that KLF2(
      )(/)(-) cells are more prone to differentiate at the early stage of the process,
      suggesting that KLF2 is a natural repressor of differentiation in vivo. Taken
      together, these studies demonstrate that KLF2 does not affect the commitment of
      multipotent stem cells into the preadipocytic lineage but rather maintains their
      preadipocyte state and thereby negatively regulates their transition into
      adipocytes.

PMID- 16101294
TI  - IL-1beta epitope mapping using site-directed mutagenesis and hydrogen-deuterium
      exchange mass spectrometry analysis.
AB  - Hu007, a humanized IgG1 monoclonal antibody, binds and neutralizes human,
      cynomolgus, and rabbit IL-1beta but only weakly binds to mouse and rat IL-1beta.
      Biacore experiments demonstrated that Hu007 and the type-I IL-1 receptor competed
      for binding to IL-1beta. Increasing salt concentrations decrease the association
      rate with only moderate effects on the dissociation rate, suggesting that long
      range electrostatics are critical for formation of the initial complex. To
      understand the ligand-binding specificity of Hu007, we have mapped the critical
      residues involved in the recognition of IL-1beta. Selected residues in cynomolgus
      IL-1beta were mutated to the corresponding residues in mouse IL-1beta, and the
      effects of the changes on binding were evaluated by surface plasmon resonance
      measurements using Biacore. Specifically, substitution of F150S decreased binding
      affinity by 100-fold, suggesting the importance of hydrophobic interactions in
      stabilizing the antibody/antigen complex. Substitution of three amino acids near
      the N- and C-terminal regions of cIL-1beta with those found in mouse IL-1beta
      (V3I/S5Q/F150S) decreased the binding affinity of Hu007 to IL-1beta by about 1000
      fold. Conversely, mutating the corresponding residues in mouse IL-1beta to the
      human sequence resulted in an increase in binding affinity of about 1000-fold.
      Hydrogen-deuterium exchange/mass spectrometry analysis confirmed that these
      regions of IL-1beta were protected from exchange because of antibody binding. The
      results from this study demonstrate that Hu007 binds to a region located in the
      open end of the beta-barrel structure of IL-1beta and blocks binding of IL-1beta
      to its receptor.

PMID- 16101295
TI  - Direct interaction of multidrug efflux transporter AcrB and outer membrane
      channel TolC detected via site-directed disulfide cross-linking.
AB  - The AcrAB-TolC system exports a wide variety of drugs and toxic compounds, and
      confers intrinsic drug tolerance on Escherichia coli. The crystal structures
      suggested that AcrB and TolC directly dock with each other. However, biochemical
      and biophysical evidence of their interaction has been contradictory until
      recently. In this study, we examine the interaction sites by means of in vivo
      disulfide cross-linking between cysteine residues introduced by site-directed
      mutagenesis at the tops of the vertical hairpins of AcrB and the bottoms of the
      coiled coils of polyhistidine-tagged TolC molecules, which are structurally
      predicted docking sites. The AcrB-TolC complex formed through disulfide cross
      linking was detected when a specific pair of mutants was coexpressed in E. coli.
      Our observations suggested that the AcrB-TolC complex may be formed through a two
      step mechanism via transient tip-to-tip interaction of AcrB and TolC. The cross
      linking was not affected by AcrA, the substrate, or a putative proton coupling
      site mutation.

PMID- 16101296
TI  - Effect of nitric oxide in amyloid fibril formation on transthyretin-related
      amyloidosis.
AB  - Although oxidative stress is said to play an important role in the amyloid
      formation mechanism in several types of amyloidosis, few details about this role
      have been described. Amyloid is commonly deposited around the vessels that are
      the primary site of action of nitric oxide generated from endothelial cells and
      smooth muscle cells, so nitric oxide may be also implicated in amyloid formation.
      For this study, we examined the in vitro effect of S-nitrosylation on amyloid
      formation induced by wild-type transthyretin, a precursor protein of senile
      systemic amyloidosis, and amyloidogenic transthyretin V30M, a precursor protein
      of amyloid deposition in familial amyloidotic polyneuropathy. S-Nitrosylation of
      amyloidogenic transthyretin V30M via the cysteine at position 10 was 2 times more
      extensive than that of wild-type transthyretin in a nitric oxide-generating
      solution. Both wild-type transthyretin and amyloidogenic transthyretin V30M
      formed amyloid fibrils under acidic conditions, and S-nitrosylated transthyretins
      exhibited higher amyloidogenicity than did unmodified transthyretins. Moreover, S
      nitrosylated amyloidogenic transthyretin V30M formed more fibrils than did S
      nitrosylated wild-type transthyretin. Structural studies revealed that S
      nitrosylation of amyloidogenic transthyretin V30M induced a change in its
      conformation, as well as instability of the tetramer conformation. These results
      suggest that the nitric oxide-mediated modification of transthyretin, especially
      variant transthyretin, may play an important role in amyloid formation in senile
      systemic amyloidosis and familial amyloidotic polyneuropathy.

PMID- 16101297
TI  - A novel conotoxin from Conus delessertii with posttranslationally modified lysine
      residues.
AB  - A major peptide, de13a from the crude venom of Conus delessertii collected in the
      Yucatan Channel, Mexico, was purified. The peptide had a high content of
      posttranslationally modified amino acids, including 6-bromotryptophan and a
      nonstandard amino acid that proved to be 5-hydroxylysine. This is the first
      report of 5-hydroxylysine residues in conotoxins. The sequence analysis, together
      with cDNA cloning and a mass determination (monoisotopic mass of 3486.76 Da),
      established that the mature toxin has the sequence
      DCOTSCOTTCANGWECCKGYOCVNKACSGCTH, where O is 4-hydroxyproline, W 6
      bromotryptophan, and K 5-hydroxylysine, the asterisk represents the amidated C
      terminus, and the calculated monoisotopic mass is 3487.09 Da. The eight Cys
      residues are arranged in a pattern (C-C-C-CC-C-C-C) not described previously in
      conotoxins. This arrangement, for which we propose the designation of framework
      #13 or XIII, differs from the ones (C-C-CC-CC-C-C and C-C-C-C-CC-C-C) present in
      other conotoxins which also contain eight Cys residues. This peptide thus defines
      a novel class of conotoxins, with a new posttranslational modification not
      previously found in other Conus peptide families.

PMID- 16101298
TI  - Effect of pH on the pore forming activity and conformational stability of
      ostreolysin, a lipid raft-binding protein from the edible mushroom Pleurotus
      ostreatus.
AB  - Ostreolysin, a pore-forming protein from the edible oyster mushroom (Pleurotus
      ostreatus), is a member of the aegerolysin protein family, a novel group of small
      acidic proteins found in bacteria, molds, mushrooms, and plants. It binds to
      lipid rafts and interacts specifically with cholesterol-rich lipid domains. In
      this study, ostreolysin was classified as a single-domain all-beta-structured
      protein on the basis of cDNA sequencing. pH-induced and thermally induced
      unfolding of ostreolysin was studied by means of CD, UV absorption, and intrinsic
      tryptophan fluorescence to characterize conformational transitions associated
      with its functional properties, i.e., binding to lipid membranes, pore forming
      activity on lipid vesicles, and hemolysis. At 25 degrees C and between pH 6 and
      9, ostreolysin adopted a monomeric and thermodynamically stable nativelike
      conformation, characterized by rigid tertiary structure and predominantly beta
      sheet secondary structure. Between pH 2 and 3, the protein underwent an
      irreversible transition to a partially unfolded, molten globule-like state which
      bound ANS, and exhibited disrupted tertiary structure and enhanced non-native
      alpha-helical structure. Functional studies showed that, unlike colicins and some
      other bacterial pore-forming toxins, the acid-induced molten globule-like state
      of ostreolysin is not relevant for lipid binding and pore formation. Instead, the
      compact native state was necessary for binding to cholesterol/sphingomyelin
      multilamellar vesicles, optimally in the pH range from 6 to 7, and for pore
      formation and hemolysis, maximally between pH 7 and 8.

PMID- 16101299
TI  - The transactivation domain of the Ah receptor is a key determinant of cellular
      localization and ligand-independent nucleocytoplasmic shuttling properties.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that regulates transcription of a number of target genes upon binding ligands
      such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Large intra- and interspecies
      variations exist with respect to sensitivity to TCDD, and this could, at least in
      part, be due to a considerable variation in the AhR amino acid sequence between
      species. The N-terminal half of the AhR is well-conserved across species, whereas
      the C-terminal half exhibits a considerable degree of degeneracy. It has
      previously been shown that there are differences between the mouse (mAhR) and
      human AhR (hAhR) in terms of cellular localization, nucleocytoplasmic shuttling,
      the effect of chaperone proteins on these properties, and differences in relative
      ligand affinity. In this study, two chimeras were generated such that each had
      the N-terminal half of one receptor and the C-terminal half of the other
      receptor. The C-terminal half of the receptor, containing the transactivation
      domain, determines the cellular localization of the transiently transfected
      receptor and regulates the ability of hepatitis B virus X-associated protein 2
      (XAP2) to inhibit ligand-independent nuclear import of AhR. In addition, the
      transactivation domain (TAD) appears to determine the presence of XAP2 in the
      nuclear ligand-bound AhR/hsp90 complex prior to association with the AhR nuclear
      translocator protein (ARNT). However, the transactivation domain does not appear
      to play a role in determining relative ligand affinity of the receptor, and mAhR
      and hAhR have similar overall transactivation potential in a cell-based reporter
      system at a saturating dose of ligand. This study demonstrates for the first time
      that the transactivation domain of the AhR influences important biochemical
      properties of the N-terminal half of the AhR, and the degeneracy in the
      transactivation domain between the mAhR and the hAhR results in species-specific
      differences in receptor properties.

PMID- 16101300
TI  - Either the carboxyl- or the amino-terminal region of the human ecto-ATPase (E
      NTPDase 2) confers detergent and temperature sensitivity to the chicken ecto-ATP
      diphosphohydrolase (E-NTPDase 8).
AB  - Human ecto-ATPase (E-NTPDase 2) and chicken ecto-ATP-diphosphohydrolase (E
      NTPDase 8) are cell surface nucleotidases with two transmembranous domains, one
      each at the N- and C-termini. Hydrolysis of substrates occurs in active sites
      residing in their extracellular domains. Human ecto-ATPase activity is decreased
      by NP-40 and at temperatures higher than 37 degrees C. Reduction of activity is
      abolished by prior cross-linking of the ecto-ATPase by lectin and chemical cross
      linking agents [Knowles, A. F., and Chiang, W.-C. (2003) Arch. Biochem. Biophys.
      418, 217-227]. In contrast, the chicken ecto-ATP-diphosphohydrolase is not
      inhibited by NP-40, and activity is approximately 2-fold higher at 55 degrees C.
      To determine if the transmembranous domains of the two E-NTPDases mediate their
      respective responses to detergents and high temperature, we first constructed a
      chimera (ck-hu ACR5) in which the C-terminus of the chicken ecto-ATP
      diphosphohydrolase is substituted by the corresponding region of the human ecto
      ATPase. While this chimera displays many similar enzymatic characteristics as the
      parental chicken ecto-ATP-diphosphohydrolase, its inhibition by NP-40, high
      temperature, and substrate resemble that of the human ecto-ATPase, which donates
      the C-terminus including the C-terminal transmembranous domain. Additionally,
      comparison of the effects of ConA, disuccinimidyl suberate, and glutaraldehyde on
      the parental enzymes and the chimera indicated that catalysis which occurs in the
      extracellular domains of the two E-NTPDases responds differently to
      conformational constraints. Enzyme activity of a second chimera (ck-hu ACR1) in
      which the N-terminus of the chicken ecto-ATP-diphosphohydrolase is substituted by
      the corresponding region of the human ecto-ATPase is also inhibited by NP-40 and
      is less active at 55 degrees C; however, its temperature dependence differs from
      that of ck-hu ACR5. These results indicate that (1) the C- and N-termini of the
      two E-NTPDases encompassing the two transmembranous domains are important
      elements in determining the sensitivity of the human ecto-ATPase to NP-40 and
      high temperatures; (2) incorporation of either the C- or N-terminus of the human
      ecto-ATPase alone in the chicken ecto-ATP-diphosphohydrolase is sufficient to
      impart negative regulation on ATP hydrolysis due to membrane perturbation; and
      (3) interactions of the two sets of heterologous transmembranous domains are not
      equivalent, which are most likely related to their different amino acid
      sequences.

PMID- 16101301
TI  - Thermal dissociation and unfolding of insulin.
AB  - The thermal stability of human insulin was studied by differential scanning
      microcalorimetry and near-UV circular dichroism as a function of zinc/protein
      ratio, to elucidate the dissociation and unfolding processes of insulin in
      different association states. Zinc-free insulin, which is primarily dimeric at
      room temperature, unfolded at approximately 70 degrees C. The two monomeric
      insulin mutants Asp(B28) and Asp(B9),Glu(B27) unfolded at higher temperatures,
      but with enthalpies of unfolding that were approximately 30% smaller. Small
      amounts of zinc caused a biphasic thermal denaturation pattern of insulin. The
      biphasic denaturation is caused by a redistribution of zinc ions during the
      heating process and results in two distinct transitions with T(m)'s of
      approximately 70 and approximately 87 degrees C corresponding to monomer/dimer
      and hexamer, respectively. At high zinc concentrations (>or=5 Zn(2+)
      ions/hexamer), only the hexamer transition is observed. The results of this study
      show that the thermal stability of insulin is closely linked to the association
      state and that the zinc hexamer remains stable at much higher temperatures than
      the monomer. This is in contrast to studies with chemical denaturants where it
      has been shown that monomer unfolding takes place at much higher denaturant
      concentrations than the dissociation of higher oligomers [Ahmad, A., et al.
      (2004) J. Biol. Chem. 279, 14999-15013].

PMID- 16101302
TI  - Spectroscopic studies of photosystem II in chlorophyll d-containing Acaryochloris
      marina.
AB  - Photosystem II (PSII) electron transfer (ET) in the chlorophyll d-containing
      cyanobacterium Acaryochloris marina (A. marina) was studied by time-resolved
      electron paramagnetic resonance (EPR) spectroscopy at room temperature,
      chlorophyll fluorescence, and low-temperature optical spectroscopy. To maximize
      the ability to measure PSII ET in the intact cells of this organism, growth
      conditions were optimized to provide the highest specific O(2) activity and the
      instrumental parameters for the EPR measurements of tyrosine Z (Y(Z)) reduction
      were adjusted to give the best signal-to-noise over spectral resolution. Analysis
      of the Y(Z)(*) reduction kinetics revealed that ET to the oxygen-evolving complex
      on the donor side of PSII in A. marina is indistinguishable from that in higher
      plants and other cyanobacteria. Likewise, the charge recombination kinetics
      between the first plastoquinone acceptor Q(A) and the donor side of PSII
      monitored by the chlorophyll fluorescence decay on the seconds time scale are not
      significantly different between A. marina and non-chlorophyll d organisms, while
      low-temperature optical absorption spectroscopy identified the primary electron
      acceptor in A. marina as pheophytin a. The results indicate that, if the PSII
      primary electron donor in A. marina is made up of chlorophyll d instead of
      chlorophyll a, then there must be very different interactions with the protein
      environment to account for the ET properties, which are similar to higher plants
      and other cyanobacteria. Nevertheless, the water oxidation mechanism in A. marina
      is kinetically unaltered.

PMID- 16101303
TI  - Staphylococcus aureus sortase transpeptidase SrtA: insight into the kinetic
      mechanism and evidence for a reverse protonation catalytic mechanism.
AB  - The Staphylococcus aureus transpeptidase SrtA catalyzes the covalent attachment
      of LPXTG-containing virulence and colonization-associated proteins to cell-wall
      peptidoglycan in Gram-positive bacteria. Recent structural characterizations of
      staphylococcal SrtA, and related transpeptidases SrtB from S. aureus and Bacillus
      anthracis, provide many details regarding the active site environment, yet raise
      questions with regard to the nature of catalysis and active site cysteine thiol
      activation. Here we re-evaluate the kinetic mechanism of SrtA and shed light on
      aspects of its catalytic mechanism. Using steady-state, pre-steady-state,
      bisubstrate kinetic studies, and high-resolution electrospray mass spectrometry,
      revised steady-state kinetic parameters and a ping-pong hydrolytic shunt kinetic
      mechanism were determined for recombinant SrtA. The pH dependencies of kinetic
      parameters k(cat)/K(m) and k(cat) for the substrate Abz-LPETG-Dap(Dnp)-NH(2) were
      bell-shaped with pK(a) values of 6.3 +/- 0.2 and 9.4 +/- 0.2 for k(cat) and 6.2
      +/- 0.2 and 9.4 +/- 0.2 for k(cat)/K(m). Solvent isotope effect (SIE)
      measurements revealed inverse behavior, with a (D)2(O)k(cat) of 0.89 +/- 0.01 and
      a (D)2(O)(k(cat)/K(m)) of 0.57 +/- 0.03 reflecting an equilibrium SIE. In
      addition, SIE measurements strongly implicated Cys184 participation in the
      isotope-sensitive rate-determining chemical step when considered in conjunction
      with an inverse linear proton inventory for k(cat). Last, the pH dependence of
      SrtA inactivation by iodoacetamide revealed a single ionization for inactivation.
      These studies collectively provide compelling evidence for a reverse protonation
      mechanism where a small fraction (ca. 0.06%) of SrtA is competent for catalysis
      at physiological pH, yet is highly active with an estimated k(cat)/K(m) of >10(5)
      M(-)(1) s(-)(1).

PMID- 16101304
TI  - Integrated insights from simulation, experiment, and mutational analysis yield
      new details of LacI function.
AB  - Protein structural change underlies many signal transduction processes. Although
      end-state structures are known for various allosteric proteins, intermediates are
      difficult to observe. Recently, targeted molecular dynamics simulation (TMD) was
      used to examine the conformational transition and predict relevant intermediates
      for wild-type lactose repressor (LacI). A catalog of involved residues suggests
      that the transition of this homodimer is asymmetric and that K84 is a prominent
      participant in the dynamic N-subdomain interface. Previous experiments indicated
      that hydrophobic substitutions at position 84 engender slowed, biphasic inducer
      binding kinetics, which might reflect the same phenomena observed in TMD. Here,
      we report biochemical confirmation that DNA and inducer binding remain
      allosterically linked in K84A and K84L, albeit with a differential smaller than
      that found in wild-type LacI. Other features of these mutant proteins are
      consistent with an allosteric conformational shift that approximates that of the
      wild type. As a consequence, these repressors can be utilized to explore an
      unanswered question about LacI function: How many inducers (one or two per dimer)
      are required to diminish operator affinity? The biphasic natures of the K84L and
      K84A inducer association rates allow direct correlation between the two distinct
      inducer binding events and operator release. Indeed, the kinetics of operator
      release for the K84A and K84L closely parallel those for the second inducer
      binding event. Together with implications from previous equilibrium results for
      wild-type and mutant proteins, these kinetic data demonstrate that binding of two
      inducers per dimeric DNA binding unit is required to release the operator in
      these variant LacI proteins.

PMID- 16101305
TI  - Interplay of isoprenoid and peptide substrate specificity in protein
      farnesyltransferase.
AB  - Protein farnesyltransferase (FTase) catalyzes the post-translational modification
      of many important cellular proteins, and is a potential anticancer drug target.
      Crystal structures of the FTase ternary complex illustrate an unusual feature of
      this enzyme, the fact that the isoprenoid substrate farnesyl diphosphate (FPP)
      forms part of the binding site for the peptide substrate. This implies that
      changing the structure of FPP could alter the specificity of the FPP-FTase
      complex for peptide substrates. We have found that this is the case; a newly
      synthesized FPP analogue, 3-MeBFPP, is a substrate with three peptide
      cosubstrates, but is not an effective substrate with a fourth peptide (dansyl
      GCKVL). Addition of this analogue also inhibits farnesylation of dansyl-GCKVL by
      FPP. Surprisingly, the differential substrate abilities of these four peptides
      with FPP-FTase and 3-MeBFPP-FTase complexes do not correlate with their binding
      affinities for these isoprenoid-enzyme complexes. The possible mechanistic
      rationales for this observation, along with its potential utility for the study
      of protein prenylation, are discussed.

PMID- 16101306
TI  - Switches, catapults, and chaperones: steady-state kinetic analysis of Hsp70
      substrate interactions.
AB  - Hsp70 chaperones are heterotropic allosteric systems in which ATP and misfolded
      or aggregated polypeptides are the activating ligands. To gain insight into the
      mechanism by which ATP and polypeptides regulate Hsp70 chaperone activity, the
      effect of a short peptide on the K(M) for ATP was analyzed using the Escherichia
      coli Hsp70 called DnaK. In the absence of peptide, the K(-P)(M) for ATP is 52 +/-
      11 nM, whereas this value jumps to 14.6 +/- 1.6 microM in the presence of
      saturating peptide. This finding supports a mechanism in which ATP binding drives
      the chaperone in one direction and peptide binding pushes the chaperone back in
      the opposite direction (and thus increases K(M)), according to ATP + DnaK.P <==>
      ATP.DnaK.P <==> ATP.DnaK* + P, where ATP.DnaK.P is an intermediate from which
      competing ATP hydrolysis occurs (ATP.DnaK.P --> ADP.DnaK.P). We show that this
      branched mechanism can even explain how DnaK hydrolyzes ATP in the absence of
      peptide and that the true rate constant for DnaK-mediated ATP hydrolysis (k(hy))
      in the absence of peptide may be as high as 0.5 s(-)(1) (rather than 5 x 10(-)(4)
      s(-)(1) as often stated in the literature). What happens is that a conformational
      equilibrium outcompetes ATP hydrolysis and effectively reduces the concentration
      of the intermediate by a factor of a thousand, resulting in the following
      relation: k(cat) = k(hy)/1000 = 5 x 10(-)(4) s(-)(1). How polypeptide substrates
      and the co-chaperone DnaJ modulate DnaK to achieve its theoretical maximal rate
      of ATP hydrolysis, which we suggest is 0.5 s(-)(1), is discussed.

PMID- 16101307
TI  - Identification in the mold Hypocrea jecorina of the first fungal D-galacturonic
      acid reductase.
AB  - A d-galacturonic acid reductase and the corresponding gene were identified from
      the mold Hypocrea jecorina (Trichoderma reesei). We hypothesize that the enzyme
      is part of a fungal d-galacturonic acid catabolic pathway which has not been
      described previously and which is distinctly different from the bacterial
      pathway. H. jecorina grown on d-galacturonic acid exhibits an NADPH-dependent d
      galacturonic acid reductase activity. This activity is absent when the mold is
      grown on other carbon sources. The d-galacturonic acid reductase was purified,
      and tryptic digests of the purified protein were sequenced. The open reading
      frame of the corresponding gene was then cloned from a cDNA library. The open
      reading frame was functionally expressed in the yeast Saccharomyces cerevisiae. A
      histidine-tagged protein was purified, and the enzyme kinetics were
      characterized. The enzyme converts in a reversible reaction from d-galacturonic
      acid and NADPH to l-galactonic acid and NADP. The enzyme also exhibits activity
      with d-glucuronic acid and dl-glyceraldehyde.

PMID- 16101308
TI  - Photoaffinity labeling with 8-azidoadenosine and its derivatives: chemistry of
      closed and opened adenosine diazaquinodimethanes.
AB  - The reactive intermediate produced upon photolysis of 8-azidoadenosine was
      studied by chemical trapping studies, laser flash photolysis with UV-vis and IR
      detection, and modern computational chemistry. It is concluded that photolysis of
      8-azidoadenosine in aqueous solution releases the corresponding singlet nitrene
      which rapidly tautomerizes to form a closed adenosine diazaquinodimethane in less
      than 400 fs. A perbenzoylated derivative of 8-azidoadenosine cannot undergo this
      tautomerization, and instead, it fragments upon photolysis to form an opened
      adenosine diazaquinodimethane. The singlet nitrene is too short-lived to be
      observed and, thus, to relax to the lowest triplet state or to become covalently
      attached to targeted biological macromolecules. The pivotal closed adenosine
      diazaquinodimethane, the product of nitrene tautomerization, has a lifetime of
      ca. 1 min or longer in water and in HEPES buffer at ambient temperature. However,
      this intermediate reacts rapidly with good nucleophiles such as amines, thiols,
      and phenolates, and significantly more slowly with weak nucleophiles such as
      alcohols and water. On the basis of these studies, it is clear that the closed
      adenosine diazaquinodimethane, and not the singlet or triplet nitrene, is the
      pivotal reactive intermediate involved in photolabeling and cross-linking studies
      using the 8-azidoadenosine family of photoaffinity labeling reagents.

PMID- 16101309
TI  - Predicting the binding affinities of misacylated tRNAs for Thermus thermophilus
      EF-Tu.GTP.
AB  - The free energies for the binding of 20 different unmodified Escherichia coli
      elongator aminoacyl-tRNAs to Thermus thermophilus elongation factor Tu (EF-Tu)
      were determined. When combined with the binding free energies for the same tRNA
      bodies misacylated with either valine or phenylalanine determined previously
      [Asahara, H., and Uhlenbeck, O. C. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 3499
      3504], these data permit the calculation of the contribution of each esterified
      amino acid to the total free energy of binding of the complex. The two data sets
      can also be used to calculate the free energy of binding of EF-Tu to any
      misacylated E. coli tRNA, and the values agree well with previously published
      experimental values. In addition, a survey of active misacylated suppressor tRNAs
      suggests that a minimal threshold of binding free energy for EF-Tu is required
      for suppression to occur.

PMID- 16101310
TI  - DNA minor groove adducts formed by a platinum-acridine conjugate inhibit
      association of tata-binding protein with its cognate sequence.
AB  - PT-ACRAMTU ([PtCl(en)(ACRAMTU-S)](NO(3))(2), en = ethane-1,2-diamine, ACRAMTU = 1
      [2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) is a cytotoxic platinum
      acridine conjugate previously shown to form adducts with the N3 endocyclic
      nitrogen of adenine in the DNA minor groove. This unusual observation and our
      prior determination of the pronounced 5'-TA/TA base-step affinity of the drug
      have prompted us to investigate effects of these adducts on DNA minor groove
      binding proteins. Here, we used electrophoretic mobility shift assays to study
      the recognition of a PT-ACRAMTU-modified TATA box sequence by TATA-binding
      protein (TBP). The frequency of PT-ACRAMTU adducts in the minor groove of the
      TATA box was varied by selective elimination of potential major groove and minor
      groove binding sites in a 24-bp probe sequence through incorporation of deaza
      nucleobases. The most dramatic effect on TBP binding was observed in a duplex
      substituted with 7-deaza-G and 7-deaza-A, which reduced binding by as much as 73%
      compared to an unplatinated duplex. In contrast, elimination of A-N3 binding
      sites had no significant effect on TBP binding, suggesting that minor groove
      adducts of PT-ACRAMTU are the cause of inhibition. This notion was further
      corroborated by efficient platinum-mediated photo-cross-linking of the drug
      modified DNA to TBP. PT-ACRAMTU appears to be the first platinum-based drug
      capable of targeting DNA sequences critical for transcription initiation. The
      biological consequences of PT-ACRAMTU's minor groove adducts are discussed.

PMID- 16101311
TI  - The C-terminal domain of the beta cell homeodomain factor Nkx6.1 enhances
      sequence-selective DNA binding at the insulin promoter.
AB  - The Hox-like factor Nkx6.1 is required for the formation and secretory function
      of insulin-producing beta cells, and has the capacity to activate or repress the
      transcription of relevant target genes in a DNA-context dependent manner. A key
      determinant of transcriptional activity by Nkx6.1 may be its C terminus, which
      has been suggested to interfere with DNA binding. To determine how the C terminus
      modulates homeodomain binding, we assessed the nature of Nkx6.1-DNA interactions
      at the insulin promoter. By quantitative gel shift analysis, we demonstrate that
      although the C terminus of Nkx6.1 mitigates the affinity of the homeodomain for
      DNA slightly (about 2-fold), it enhances the selectivity of the homeodomain for
      TAAT DNA sequences nearly 10-fold. By reporter gene analysis, this selectivity is
      also functionally preserved in mammalian cells in vivo. Based on deletional and
      mutational studies, the sequence selectivity imparted by the C terminus appears
      to be mediated by a stretch of highly conserved residues between amino acids 318
      and 338. Strikingly, these residues impart minimal changes to the secondary
      structure of the unbound protein as assessed by circular dichroism spectroscopy,
      suggesting that conformational adjustments of the homeodomain that occur upon
      binding to DNA may play a more important role in sequence selectivity. The C
      terminus of Nkx6.1 also functions in a modular fashion, as it can confer similar
      DNA binding properties when fused to the heterologous homeodomain of Pdx-1. Taken
      together, our data suggest a model whereby the Nkx6.1 C terminus may function in
      a regulatory manner by imposing specific functional constraints upon the protein.
      These constraints may serve to modulate the potential of Nkx6.1 to both recognize
      target genes and regulate their transcription.

PMID- 16101312
TI  - Isothermal titration calorimetry studies of the binding of the antimicrobial
      peptide gramicidin S to phospholipid bilayer membranes.
AB  - The binding of the amphiphilic, positively charged, cyclic beta-sheet
      antimicrobial decapeptide gramicidin S (GS) to various lipid bilayer model
      membrane systems was studied by isothermal titration calorimetry. Large
      unilamellar vesicles composed of the zwitterionic phospholipid 1-palmitoyl-2
      oleoylphosphatidylcholine or the anionic phospholipid 1-palmitoyl-2
      oleoylphosphatidylglycerol, or a binary mixture of the two, with or without
      cholesterol, were used to mimic the lipid compositions of the outer monolayers of
      the lipid bilayers of mammalian and bacterial membranes, respectively. Dynamic
      light scattering results suggest the absence of major alterations in vesicle size
      or appreciable vesicle fusion upon the binding of GS to the lipid vesicles under
      our experimental conditions. The binding isotherms can be reasonably well
      described by a one-site binding model. GS is found to bind with higher affinity
      to anionic phosphatidylglycerol than to zwitterionic phosphatidylcholine
      vesicles, indicating that electrostatic interactions in the former system
      facilitate peptide binding. However, the presence of cholesterol reduced binding
      only slightly, indicating that the binding of GS is not highly sensitive to the
      order of the phospholipid bilayer system. Similarly, the measured positive
      endothermic binding enthalpy (DeltaH) varies only modestly (2.6 to 4.4 kcal/mol),
      and the negative free energy of binding (DeltaG) also remains relatively constant
      (-10.9 to -12.1 kcal/mol). The relatively large but invariant positive binding
      entropy, reflected in relatively large TDeltaS values (13.4 to 16.4 kcal/mol),
      indicates that GS binding to phospholipid bilayers is primarily entropy driven.
      Finally, the relative binding affinities of GS for various phospholipid vesicles
      correlate relatively well with the relative lipid specificity for GS interactions
      with bacterial and erythrocyte membranes observed in vivo.

PMID- 16101313
TI  - Structural and dynamic characteristics of a partially folded state of ubiquitin
      revealed by hydrogen exchange mass spectrometry.
AB  - Structural and dynamic properties of a partially folded conformation (A-state) of
      ubiquitin are studied using amide hydrogen exchange in solution (HDX) and mass
      spectrometric detection. A clear distinction between the native state of the
      protein and the A-state can be made when HDX is carried out in a semicorrelated
      regime. Convoluted exchange patterns are interpreted with the aid of HDX
      simulations in a three-state system (highly structured, partially unstructured,
      and fully unstructured states). The data clearly indicate a highly dynamic
      character of the non-native state. Furthermore, combination of HDX and protein
      ion fragmentation in the gas phase [by means of collision-induced dissociation
      (CAD)] is used to evaluate the conformational stability of various protein
      segments specifically in the molten globular state. Chain flexibility appears to
      be distributed very unevenly in this non-native conformation. The highest degree
      of structural disorder is displayed by the C-terminal segment (Gly(53)-Gly(76)),
      which was previously suggested to form a transient alpha-helix. The least dynamic
      segment of ubiquitin in the A-state is Thr(9)-Glu(18) (which was previously
      suggested to form a stable nativelike beta-strand), with the adjacent segments
      exhibiting somewhat diminished conformational stability. The study also
      demonstrates the power of mass spectrometry as a tool in providing conformer
      specific information about the structure and dynamics of both native and non
      native protein states coexisting in solution under equilibrium.

PMID- 16101314
TI  - Catalytic mechanism of hamster arylamine N-acetyltransferase 2.
AB  - Arylamine N-acetyltransferases (NATs) catalyze an acetyl group transfer from
      AcCoA to primary arylamines, hydrazines, and hydrazides and play a very important
      role in the metabolism and bioactivation of drugs, carcinogens, and other
      xenobiotics. The reaction follows a ping-pong bi-bi mechanism. Structure analysis
      of bacterial NATs revealed a Cys-His-Asp catalytic triad that is strictly
      conserved in all known NATs. Previously, we have demonstrated by kinetic and
      isotope effect studies that acetylation of the hamster NAT2 is dependent on a
      thiolate-imidazolium ion pair (Cys-S(-)-His-ImH(+)) and not a general acid-base
      catalysis. In addition, we established that, after formation of the acetylated
      enzyme intermediate, the active-site imidazole, His-107, is likely deprotonated
      at physiological pH. In this paper, we report steady-state kinetic studies of
      NAT2 with two acetyl donors, acetyl coenzyme A (AcCoA) and p-nitrophenyl acetate
      (PNPA), and four arylamine substrates. The pH dependence of k(cat)/K(AcCoA)
      exhibited two inflection points at 5.32 +/- 0.13 and 8.48 +/- 0.24, respectively.
      The pK(a) at 5.32 is virtually identical with the previously reported pK(a) of
      5.2 for enzyme acetylation, reaffirming that the first half of the reaction is
      catalyzed by a thiolate-imidazolium ion pair in the active site. The inflection
      point at 8.48 indicates that a pH-sensitive group on NAT2 is involved in AcCoA
      binding. A Bronsted plot constructed by the correlation of log k(4) and log
      k(H)2(O) with the pK(a) for each arylamine substrate and water displays a linear
      free-energy relationship in the pK(a) range from -1.7 (H(2)O) to 4.67 (PABA),
      with a slope of beta(nuc) = 0.80 +/- 0.1. However, a further increase of the
      pK(a) from 4.67 (PABA) to 5.32 (anisidine) resulted in a 2.5-fold decrease in the
      k(4) value. Analysis of the pH-k(cat)/K(PABA) profile revealed a pK(a) of 5.52 +/
      0.14 and a solvent kinetic isotope effect (SKIE) of 2.01 +/- 0.04 on
      k(cat)/K(PABA). Normal solvent isotope effects of 4.8 +/- 0.1, 3.1 +/- 0.1, and
      3.2 +/- 0.1 on the k(cat)/K(b) for anisidine, pABglu, and PNA, respectively, were
      also determined. These observations are consistent with a deacetylation mechanism
      dominated by nucleophilic attack of the thiol ester for arylamines with pK(a)
      values <or=5.5 to deprotonation of a tetrahedral intermediate for arylamines with
      pK(a) values >or=5.5. The general base is likely His-107 because the His-107 to
      Gln and Asn mutants were found to be devoid of catalytic activity. In contrast,
      an increase in pH-dependent hydrolysis of the acetylated enzyme was not observed
      over a pH range of 5.2-7.5. On the basis of these observations, a catalytic
      mechanism for the acetylation of arylamines by NAT2 is proposed.

PMID- 16101315
TI  - Traffic air pollution -- is it safe to be a traffic policeman or professional
      driver?

PMID- 16101316
TI  - A review of proteomics in cancer research.
AB  - The most functional compartment encoded by the genome is proteome. Therefore
      study of proteome i.e. proteomics is the promising approach in identification,
      separation and quantitation of functional changes. It aims to gain a
      comprehensive understanding of the expressions, modifications, interactions, and
      regulation of proteins in cells. The power of two-dimensional electrophoresis and
      advances in mass spectrometric techniques, combined with sequence data base
      correlation, has enabled speed and accuracy in identification of proteins in
      complex mixtures. Therefore, proteomics may provide a better understanding of the
      molecular basis of cancer growth, with identification of potential pathological
      markers and therapeutic targets. Tobacco related cancers are the major health
      hazard in Asian countries; the proteomics approach should be employed for
      understanding the underlying disease processes and hopefully reveal important
      clues for identifying high risk individuals and early changes during malignant
      transformation.

PMID- 16101317
TI  - Dietary cardamom inhibits the formation of azoxymethane-induced aberrant crypt
      foci in mice and reduces COX-2 and iNOS expression in the colon.
AB  - Recently, considerable attention has been focused on identifying naturally
      occurring chemopreventive compounds capable of inhibiting, retarding, or
      reversing the multi-step carcinogenesis. The primary aim of the present study was
      to identify the effects of a commonly consumed spice, viz., cardamom against
      azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) in Swiss Albino
      mice. The secondary aim, was to explore the ability of cardamom to modulate the
      status of proliferation and apoptosis, and to understand its role in altering
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression.
      Male Swiss albino mice were injected with AOM (dose: 5mg/Kg body weight) or
      saline (Group 1) weekly once for two weeks. The AOM-injected mice were randomly
      assigned to two groups (Groups 2 and 3). While all the groups were on standard
      lab chow, Group 3 received oral doses of 0.5% cardamom, in aqueous suspension,
      daily for 8 weeks. Following treatment, significant reduction in the incidences
      of aberrant crypt foci (p<0.05) was observed. This reduction in ACF was
      accompanied by suppression of cell proliferation (mean Brdu LI in carcinogen
      control =13.91+/-3.31, and 0.5% cardamom =2.723+/-0.830) and induction of
      apoptosis (mean AI in carcinogen control=1.547+/-0.42 and 0.5% cardamom = 6.61+/
      0.55). Moreover, reduction of both COX-2 and iNOS expression was also observed.
      These results suggest that aqueous suspensions of cardamom have protective
      effects on experimentally induced colon carcinogenesis. Cardamom as a whole and
      its active components require further attention if the use of this spice is to be
      recommended for cancer prevention.

PMID- 16101318
TI  - Is it relevant to screen women younger than 26 years for precancerous and
      malignant cervical lesions ?
AB  - Cervical cancer is a serious health problem and most of the cases occur in less
      developed countries where effective screening systems are lacking. The aim of our
      present study is to delineate the age for early detection of precancerous
      cervical lesions. Cervical smears were screened (Pap test) over a period of four
      and half years from January 2000 to June 2004. The pattern of lesions was found
      to be almost same among the age groups of 26 to 35 years and 36 to 45 years. This
      result tempted us to think that detection of cervical lesions at an early age
      younger than 26 years may be an important step forward towards complete cure.

PMID- 16101319
TI  - Attitudes of patients to alternative medicine for cancer treatment.
AB  - Awareness of attitudes to different types of medicine is very important for
      estabishment of cancer prevention programs. Alternative medicine has become an
      important feature of oncology regardless of geographic region, and in India, the
      majority of cancer patients present at late advance stage of disease when
      curative treatment cannot be initiated. Given the lack of facilities it is no
      surprise that many Indian cancer patients try various complementary and
      alternative medicines, depsite the fact that little is known about their
      therapeutic efficacy and toxicity. A study was conducted in 300 biopsy proven
      cancer patients undergoing alternative cancer therapy with Psorinum in Kolkata.
      The main aim of the study was to analyze the patients'/caregivers narratives
      regarding the therapy they have been trying. One hundred and ninety five patients
      (65%) have consulted their oncologists before trying this therapy. About 18.5% of
      the patients expressed satisfaction with the therapy due to the holistic nature
      and team approach employed for patient management. The cost of the therapy was
      within the reach of many cancer patients belonging to the underprivileged segment
      of the society, contributing to its immense popularity in Kolkata. Whether this
      can be translated into a willingness to use similar natural compounds for cancer
      prevention and treatment purposes now needs to be analysed.

PMID- 16101320
TI  - Time trends in the occurrence of major GI cancers in Iran.
AB  - OBJECTIVE: The aim of this study was to study the changes in occurrence of
      esophageal, stomach and colon cancers (cancers of interest) over the last 30
      years in Iran. MATERIAL AND METHODS: Cancer cases referred to two main cancer
      centers in the country (the Shiraz cancer center and the Tehran cancer center)
      during last 30 years and published by the two centers were utilized. Morbidity
      odds ratios (MOR) were used to study trend in the occurrence of each cancer site
      in each center. For this purpose the cancers of interest were considered as
      cases; childhood cancers as controls; and calendar year as exposure. A regression
      line was fitted to morbidity odds ratios over years and the slope of the
      regression line was considered to indicate the overall trend. MORs and 95% CIs
      comparing the last five and first five years were computed to measure the
      magnitude of the change over time. RESULT: The overall trend for esophageal
      cancer was decrease (slopes = -0.02 for Shiraz and -0.03 for Tehran); for stomach
      was increase (slopes = 0.04 for Shiraz and 0.08 for Tehran), and for colon cancer
      was sharp increase (slopes = 0.02 for Shiraz and 0.10 for Tehran). The magnitude
      of changes showed stomach cancer to increase by 35% in Shiraz (MOR = 1.35 with
      95% CI 1.1, 1.65) and 13% in Tehran (MOR = 1.13 with 95% CI 0.96, 1.38),
      esophageal cancer to decrease by 20% in Shiraz (MOR = 0.82 with 95% CI 0.62,
      1.11) and 50% in Tehran (MOR = 0.52 with 95% CI 0.45, 0.60), and colon cancer to
      increase by 65% in Shiraz (MOR = 1.65 with 95% CI 1.26, 2.16) and 82% in Tehran
      (MOR = 1.82 with 95% CI 1.52, 2.25). CONCLUSION: During the last thirty years the
      occurrence of major GI cancers has changed in Iran with sharp increase in colon
      cancer, slight to moderate increase in stomach cancer and sharp decrease in
      esophageal cancer.

PMID- 16101321
TI  - Survival analyses of breast cancer patients--the Shaukat Khanum Memorial
      experience.
AB  - Seven hundred subjects with breast cancer malignancies were followed up in time
      from December 1994 to December 2002 to determine survival distributions between
      sub-groups of breast cancer patients who had undergone surgical resection of the
      tumor followed by adjuvant treatment. Tumor size, nodal status, and Estrogen
      Receptor (ER) status at the time of presentation were ascertained. Tumors were
      classified according to the TNM system of the American Joint Committee on Cancer
      (AJCC), sixth edition, and grouped into T1/T2 and T3/T4; lymph nodes were
      categorized as N0 (node-negative) and N1, N2, and N3 combined (node-positive).
      The endpoint of interest for disease-free survival was relapse, and for overall
      survival, it was death. The Wilcoxon statistics for testing the equality of
      disease-free survival distributions between groups of patients with tumor size
      greater than 5 versus less than or equal to 5 cm, node-positive versus node
      negative, and ER-positive versus ER-negative were found to be statistically
      significant (p < 0.05). For overall survival, substantial differences were found
      between groups of patients stratified according to tumor diameter and nodal
      involvement, but none for ER status.

PMID- 16101322
TI  - Geographical variation in the epidemiology of esophageal cancer in Pakistan.
AB  - STUDY OBJECTIVES: To evaluate whether factors such as the geographic area of
      residence, sex, and anatomic subsite of esophagus can prognosticate the
      histologic subtype of esophagus cancer. DESIGN: To study the major histologic
      subtypes of esophagus cancer stratified by various factors through multivariate
      analyses using morphology as the dependent factor and gender, province, and
      subsite of esophagus as independent factors. SETTING: A tertiary care cancer
      hospital situated in the city of Lahore in Pakistan. PATIENTS: Three hundred and
      thirty five patients diagnosed either with esophageal squamous cell carcinoma or
      adenocarcinoma, from December 1994 to April 2004, were included. Subjects were
      residents of either Punjab or the Northwest Frontier Province in Pakistan. MAIN
      RESULTS: An excessive likelihood of development of squamous cell carcinoma versus
      adenocarcinoma was established for the Northwest Frontier Province as compared to
      Punjab (odds ratio 2.7, 95 percent confidence interval: 1.2, 6.2, p = 0.02), and
      in the upper-third of the esophagus relative to the lower-third of the organ
      (odds ratio 8.8, 95 percent confidence interval: 2.8, 28.3, p < 0.001).
      CONCLUSIONS: This histologic variation may be explained by environmental and
      lifestyle factors peculiar to geographical regions.

PMID- 16101323
TI  - Determination of sunburn and skin cancer risk of outpatients in a dermatology
      polyclinic.
AB  - Public health experts and medical professionals continue to issue warnings to
      people about the dangers of ultraviolet (UV) radiation fromthe sun, tanning beds,
      and sun lamps. Skin cancer is more common than any other type of cancer and
      exposure to sun is known to contribute to all three major types, namely, basal
      cell carcinoma, squamous-cell carcinoma and cutaneous melanoma. While skin cancer
      has been associated with sunburn, moderate tanning may also exert an influence.
      Seven steps to safer sunning are avoiding the sun, using a sunscreen, wearing a
      hat, wearing sunglasses, covering up, avoiding artificial tanning, and checking
      skin regularly. The present study was performed to examine the knowledge,
      attitudes, and risk factors of individuals concerning skin cancer. A descriptive
      survey was conducted among 475 patients randomly selected from the Dermatology
      Polyclinic of Ege University. A self-administered questionnaire was used to
      investigate their knowledge about skin cancer. A total of 297 female and 178 male
      participants were questioned, with a mean age of 32.48 +15.12. Some 36.8% had
      skin type II and 39.8% type III. The most common hair and eye color were brown,
      respectively at 56.0% and 58.7%. 79.8% had a mole(s), 19.2% had birthmark. A
      total of 8 of the 475 participants consulted for sunburns (1.7%). Glasses were
      the most popular preventive behaviour (28.8%). A total of 56 of the 475
      outpatients questioned did not use any protective measure. Individuals need to be
      better educated on the dangers of the sun and sun protection as well as skin
      cancer.

PMID- 16101324
TI  - Vitamin-D receptor (VDR) gene (Fok-I, Taq-I and Apa-I) polymorphisms in healthy
      individuals from north Indian population.
AB  - The vitamin-D endocrine system is involved in a wide variety of biological
      processes including bone metabolism, modulation of immune responses, and
      regulation of cell proliferation and differentiation. Variation in this endocrine
      system have, thus, been linked to several common diseases, including
      osteoarthritis (OA), diabetes, cancer, cardiovascular ailments, urolithiasis and
      tuberculosis. Activity of Vit-D is mediated by the vitamin D receptor (VDR), a
      ligand dependent receptor. VDR gene polymorphisms thus represent strong
      positional candidates for different diseases like prostate cancer, urolithiasis,
      inflammatory bowl disease and osteoporosis. Genetic studies provide excellent
      opportunities to link molecular insights with epidemiological data and can reveal
      modest and subtle but true biological effects. The abundance of polymorphisms in
      the human genome as well as high frequencies in human populations have made them
      targets to explain variation in risk of common diseases. The present study was
      carried out to determine the distribution of VDR gene (Fok-I, Taq-I and Apa-I)
      polymorphisms using a PCR-based restriction analysis in unrelated normal healthy
      individuals from a north Indian population. We obtained allelic frequencies of
      (68.5% vs 31.5%), (66% vs 34%) and (58% vs 42%) for (F vs f), (T vs t) and (A vs
      a) alleles, with 44%, 49% and 7%, respectively, for genotypes FF, Ff and ff ,
      49%, 40% and 11% for TT, Tt and tt and 36%, 44% and 20% for AA, Aa and aa. Our
      results suggest that the frequency and distribution of the polymorphisms in India
      are substantially different from in other populations and ethnic groups. Thus the
      data signify an impact of ethnicity and provide a basis for future
      epidemiological and clinical studies.

PMID- 16101325
TI  - CYP1A1 inducing potential of airborne particulate extracts collected during a 25
      year period (1975-2000).
AB  - Samples of airborne particles from Sapporo, the capital of Hokkaido, Japan, were
      collected between 1975 and 2000. Major polycyclic aromatic hydrocarbons (PAHs)
      included in the extracts of airborne particles were investigated for their
      mutagenicity and potential for inducing drug-metabolizing enzyme cytochrome P450
      (CYP)1A1, which is considered to be responsible for the activation of PAHs in
      airborne particle extracts, as well as in cigarette smoke, to carcinogens and is
      associated with risk of several cancers. There was a dose-related increase in
      CYP1A1 activity in human lymphoblastoid cells after exposure to airborne
      particulates containing PAHs. The mutagenicity of the airborne particles
      collected in summer was lowest and for those collected in spring was lower than
      in autumn or winter. Likewise, the winter sample had the strongest CYP1A1
      inducing potential while the summer sample had the weakest. CYP1A1 inducing
      potency was strongly related to the amount of benzo(k)fluorathene (Spearman's
      rank correlation coefficient (gamma) = 0.97), benzo[a]pyrene g = 0.96),
      benzo[g,h,i]perylene (gamma = 0.94), benz[a]anthracene (g = 0.93), chrysene
      (gamma = 0.93) in the extracts during the 25-year period, while the enzyme
      activity was measurably related to the amount of pyrene (gamma = 0.64) and
      fluorathene (gamma = 0.54). During the 25-year period, CYP1A1 inducing potential
      decreased every year together with a decrease in PAHs in the airborne particle
      extracts. CYP1A1 inducing potential may be one of the most convenient biomarkers
      with which to estimate the overall carcinogenicity/mutagenicity of airborne
      particle extracts.

PMID- 16101326
TI  - Cancer occurrence in Semnan Province, Iran: results of a population-based cancer
      registry.
AB  - INTRODUCTION: suitable information of different cancers in special geographic
      areas can help define medical programs for treatment and screening of high-risk
      groups. AIMS AND METHODS: The provincial health authority reported a high
      mortality rate from upper GI cancer in the center of Iran. A comprehensive search
      was undertaken to survey and register all cases of cancer during a 5-year (1998
      2002) period among the indigenous population of Semnan Province. Diagnosis of
      cancer was based on histopathology, clinical or radiological findings, and death
      certificates. RESULTS: A total of 1732 patients with cancers (mean age 59.41% +/
      19.08% years) were found during the study. Of these, 936(54.86%) were in males.
      Crude rates were 124.8/100,000 and 112.1/100,000 for males and females,
      respectively. Age-standardized ratios (ASRs) for all cancers in males and females
      were 156/100,000 and 136/100,000 person-year, respectively. Gastric cancer was
      the most common tumor with an incidence rate of 19.7 per 100,000 people
      (ASR=27.5). In upper gastrointestinal cancers, gastric cancer was the most common
      (47.17%), followed by colon malignancies (8.1%, 9.5 per 100,000 populations),
      esophagus (6.8%, 7.9 per 100,000 populations), liver (2.4%, and 2.8 per 100,000
      populations). In women, breast, uterine and ovary, stomach and skin were the most
      common cancers. In the child population the most common tumors were of the brain,
      acute lymphocytic leukemia, and bone. CONCLUSION: Gastric cancer alone
      constitutes one-sixth of all cancers in Semnan, with the highest ASR incidence
      rate reported from Iran up to now.

PMID- 16101327
TI  - Minimal sizes of cases with a susceptible genotype and minimal odds ratios among
      susceptible individuals in case-control studies.
AB  - OBJECTIVE: Disease risk elevation due to an environmental factor only for
      individuals with a susceptible genotype is a typical example of gene-environment
      interaction. In order to identify risk factors interacting with susceptible
      genotypes in case-control studies, presumptions on minimal size of cases with the
      susceptible genotype (S (min)) and odds ratio (OR) among the susceptible
      individuals (OR(susceptible)) are useful. MODEL: Proportion of exposed cases
      (P(1)) and OR for whole cases (OR(whole)) statistically detectable in a case
      control study can be calculated in a conventional method. P(1) was assumed to be
      a weighted sum of the exposed among cases with the genotype (P(x)) and cases
      without the genotype (equal to proportion of the exposed among controls, P(0)),
      i.e., S P(x) + (1 - S) P0, where S is the size (proportion) of cases with the
      genotype. For each calculated P(1), S became the minimum (S(min)) in case of P(x)
      = 1. OR(susceptible) was calculated by {P(x) (1 - P(0))} / {(1 - P(x)) P(0)}.
      RESULTS: S(min) and OR(susceptible) were listed for the combinations of the above
      components. For example, a detectable P(1) was 0.638 for P(0)=0.5 in a case
      control study with 200 cases (N(1)) and 200 controls (N(0)), when a error of a
      two-sided test was 0.05 with an 80% of power. In case of P(1)=0.638, OR(whole)
      was 1.77, producing S(min) = 0.277 for infinite OR(susceptible). It indicates
      that an environmental factor cannot be detected in case that a high-risk genotype
      frequency is less than 0.277. INTERPRETATION: If the size of cases with a
      susceptible genotype is expected to be less than S(min), case-control studies are
      unlikely to detect a significant OR of the environmental factor.

PMID- 16101328
TI  - Lack of an association between serum level of transforming growth factor beta -1
      and stomach cancer risk in the JACC study.
AB  - Alterations in the serum concentration of transforming growth factor beta-1
      (TGFbeta1) have been observed in gastric cancer patients. No study, however, has
      ever examined the association between the serum TGFbeta1 level and stomach cancer
      prospectively. We conducted a prospective, nested case-control analysis among
      apparently healthy men and women who were followed for up to 8 years in the JACC
      Study to assess whether serum level of total TGFbeta1 is associated with a
      subsequent risk of stomach cancer. The concentration of serum TGFbeta1 in
      previously collected blood samples was analyzed by ELISA for 209 individuals in
      whom a diagnosis of stomach cancer was documented, and for 409 controls matched
      with them for gender, age and study area. Baseline blood levels of TGFbeta1 were
      not related to the risk of stomach cancer in either men or women, a finding
      unchanged even after adjustment for potential confounders. The multivariate
      adjusted odds ratio of stomach cancer in men and women was 1.10 (95% CI, 0.82 to
      1.48) and 1.09 (95% CI, 0.80 to 1.48), respectively, for each increase of 1 SD in
      the TGFbeta1 value. In conclusion, serum TGFbeta1 levels were not associated with
      increased risks of subsequent stomach cancer.gene A52C polymorphism related to
      the metabolism of long-chain fatty acids and oxidized LDL in the etiology of
      colorectal cancer.

PMID- 16101329
TI  - Association between breast cancer and vitamin C, vitamin E and selenium levels:
      results of a case-control study in India.
AB  - In women, cancer of the breast is generally the most prevalent neoplasm and cause
      of cancer death. Though a large number of women are affected with breast cancer,
      very few studies have been undertaken in India on the association between
      micronutrients and the risk of breast cancer. We conducted a hospital based case-
      control study to examine the associations of vitamin C, vitamin E and selenium
      with breast cancer. One hundred and sixty breast cancer patients and an equal
      number of normal healthy individuals constituted the study population. Venous
      blood was collected from the cases and controls for estimation of vitamin C,
      vitamin E and selenium utilizing standard procedures. Univariate logistic
      regression analysis was carried out to calculate odds ratios and confidence
      intervals. The mean vitamin C, vitamin E and selenium levels were lower in
      patients as compared to the controls. There was a 84% and 77% lower risk of
      breast cancer if the levels of vitamin C and vitamin E were increased by 1 unit,
      respectively. Similarly, there was a 7% lower risk of breast cancer if the level
      of selenium was increased by 1 unit. The results of the present study thus
      indicated a strong association of vitamin C, vitamin E and selenium with breast
      cancer in the Indian population.

PMID- 16101330
TI  - Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage
      mouse skin carcinogenesis.
AB  - Epidemiological, clinical and experimental evidence collectively suggests that Se
      in different inorganic and organic forms provides a potential cancer
      chemopreventive agent, active against several types of cancer. It can exert
      preventive activity in all the three stages of cancer: initiation, promotion and
      progression. Literature reports revealed that organoselenocyanates have more
      potential as chemopreventive agents than inorganic forms due to their lower
      toxicity. In our previous report we showed chemopreventive efficacy of
      diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation
      phases of skin and colon carcinogenesis process. The present study was undertaken
      to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in
      a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin
      carcinogenesis model. The results obtained showed significant (p<0.01) reduction
      of the incidence and number of skin papillomas, precancerous skin lesions, along
      with significant (p<0.01) elevation of phase II detoxifying enzymes (GST,
      Catalase and SOD) and inhibition of lipid peroxidation in liver and skin. Thus,
      the present data strongly suggest that diphenylmethyl selenocyanate also has the
      potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis
      mouse model, pointing to possible general efficacy.

PMID- 16101331
TI  - Coping mechanisms among long-term survivors of breast and cervical cancers in
      Mumbai, India.
AB  - Accumulated evidence indicates that the positive coping means a good quality of
      life, which will contribute significantly to improvement in the prognosis. In low
      resource settings, it is a challenge for medical teams and patient families to
      provide psychological and emotional support throughout the fight against the
      disease. This paper appraises coping mechanisms among the long-term survivors of
      breast and cervical cancers in Mumbai. Women surviving for at least five years
      were extracted from the Bombay cancer registry patient index for evaluation: a
      simple and locally developed instrument was used for In-depth Interviews (IDI's)
      at patient residences. A total of 80 survivors were interviewed but only findings
      for 52 subjects with complete information are presented in this paper. Parameters
      were studied in the order of personal, psychological, emotional, physical and
      spiritual well being of the patients. The analysis is mostly descriptive in its
      nature: qualitative analysis techniques (free listing and clustering) were
      adopted to present the data. Positive thinking, purpose in life, and strong
      family support played key roles in achieving completion of treatment then
      prolonging survival. An appropriative health seeking behaviour, good general
      medication, and emotional support from friends and family members were revealed
      to be very important factors for coping capably. An unmet need for knowledge of
      symptoms was identified, which suggests that appropriate messages should be
      generated to reach women in conventional families. Despite the small sample size,
      our findings broadly provide a base for large-scale future studies and suggest
      gaps to be filling in counselling interventions in Mumbai.

PMID- 16101332
TI  - Gastric carcinoma: 5 year experience of a single institute.
AB  - PURPOSE: Gastric cancer (GC) is the most common cause of cancer death registered
      in cancer institute. Background clinical information is important for cancer
      prevention and therefore we here present characteristics and outcome of GC
      patients, more than half coming from northern parts of Iran. MATERIALS AND
      METHODS: we retrospectively studied records patients with pathologic diagnosis of
      GC referred to the Medical Oncology Department of the Cancer Institute from 1998
      to 2003. RESULTS: Four hundred and thirteen patients were registered with GC with
      the average age of 58 and a male to female ratio of 3/1. Tumor stage based on
      AJCC was stage 2(12.5%), stage 3(22%), stage 4(63%) and 2% unknown. Most common
      site of involvement was cardia (43%). Median survival time of all patients (with
      or without treatment) was 10 months overall. Gastrectomy was performed for 214
      patients(39% with positive surgical margins), and 175 of the gastrectomised
      patients received chemotherapy. Median survival with surgery only was 7 months
      but 20 months with both surgery and chemotherapy. Only 21 patients received
      neoadjuvant chemotherapy. Median survival of patients who had response to
      preoperative chemotherapy was 30 months. By multivariate analysis lower extent of
      disease (p=0.0024), free surgical margin (p=0.0017), and chemotherapy (p=0.001)
      were associated with better prognosis. CONCLUSIONS: Only curative resection with
      free margins was associated with a survival benefit in this study. More than 80%
      of patients were diagnosed in locally advanced or metastatic stage of disease and
      even with neoadjuvant chemotherapy and salvage surgery the outcome was poor.
      Clearly more efforts need to be given to early detection of lesions to allow a
      better cure rate.

PMID- 16101333
TI  - Chemopreventive action of emblica officinalis on skin carcinogenesis in mice.
AB  - Chemoprevention with food phytochemicals is currently regarded as one of the most
      important strategies for cancer control. Emblica officinalis (Family:
      Euphorbiaceae) indigenous to India, is valued for its unique tannins and
      flavanoids, which contain very powerful antioxidant properties. The inhibition of
      tumor incidences by fruit extract of this plant has been evaluated on two-stage
      process of skin carcinogenesis in Swiss albino mice, induced by a single
      application of 7, 12-dimethyabenz(a)anthrecene (100 microg / 100 microl acetone),
      and two weeks later, promoted by repeated application of croton oil (1% in
      acetone/thrice a week) till the end of the experiment (16 weeks). The tumor
      incidence, tumor yield, tumor burdon and cumulative number of papillomas were
      found to be higher in the control (without EO treatment) as compared to
      experimental animals (EO treated). The differences in the values of the results
      of experimental groups were statistically analysed and found to be significant in
      comparison to the control group (p< 0.05). The present study demonstrates the
      chemopreventive potential of Emblica officinalis fruit extract on DMBA induced
      skin tumorigenesis in Swiss albino mice.

PMID- 16101334
TI  - Assessment of risk factors in laryngeal cancer in India: a case-control study.
AB  - Cancer of the larynx is fourteenth most common cancer in the world. Limited data
      are available from India on associations with risk factors and hence the present
      hospital based matched case-control study was conducted. Three hundred and five
      laryngeal cancer patients and an equal number of healthy controls matched for
      their age within 2 years, sex and place of residence constituted the study
      population. A pre-tested, semi-structured questionnaire was administered to each
      individual to elicit information on their socio-demographic profile, food habits
      and risk factors and dietary consumption patterns. Univariate logistic regression
      analysis and multivariate forward stepwise conditional logistic analysis were
      performed. In the univariate analysis a lower consumption of roots and tubers
      green leaf vegetable other vegetables and fruits, and higher consumption of milk,
      eggs, meat, tea, alcohol , smoking, consumption of betel leaf with tobacco as
      well as a preference for spicy and fried foods emerged as significant positive
      variables. After adjusting for education, years of use of alcohol, smoking,
      chewing of betel leaf with tobacco in the model, low green leafy vegetables and
      preference for spicy foods were found to be positively related to the risk of
      laryngeal cancer. There was a significant difference in the dietary consumption
      patterns of laryngeal cancer patients and controls, indicating a role for
      nutritional factors in the etiology of laryngeal cancer in the Indian population.

PMID- 16101335
TI  - Consistency of cytology diagnosis for cervical cancer between two laboratories.
AB  - The principal approach to the prevention of cancer of the cervix uteri has been
      through screening programmes, using the cervical smear (Pap test) to detect
      precursor lesions. The sensitivity and specificity of Pap smears depend on the
      skill of the observer in recognizing and classifying a variety of cellular
      abnormalities. We have studied the reproducibility of cytological diagnosis,
      according the Bethesda classification, made by cytologists in Khon Kaen, north
      east Thailand, and in Helsinki, Finland, on smears taken from rural women
      undergoing screening during 1994-2001. A total of 313 slides were reviewed. The
      prevalence of abnormalities was relatively high, since the series included smears
      judged abnormal in Khon Kaen or from women who developed cancer during follow-up,
      as well as a group whose smears were negative. In general, the reviewing
      cytologist in Finland evaluated more slides as abnormal than in the initial
      report. The level of agreement between the two observers was evaluated by
      calculating the coefficient of concordance (Kappa). The kappa score depended upon
      the degree of detail in the diagnosis; it was 0.43 for the presence or not of an
      epithelial abnormality (the General Categorization of the Bethesda system), and
      rather higher (0.5) for separating low grade from high grade (HSIL or worse)
      abnormalities or glandular lesions. Agreement was only fair (0.37) when the more
      detailed Bethesda categories (seven) were used. The reproducibility of cervical
      cytology evaluations is critical to the success of screening programmes, and in
      this programme in a moderate-high risk population of women in rural Thailand, we
      found that agreement between skilled observers, at the level of tests requiring
      diagnostic follow-up or not, was only moderate. The women in this study are being
      traced to evaluate the true sensitivity of screening in terms of the lesions
      found on histology, during a prolonged follow up of 4 or more years.

PMID- 16101336
TI  - Hepatitis virus B is not a risk factor in hepatoblastoma patients.
AB  - The prevalence of primary liver cancer varies throughout the world.
      Hepatoblastoma is the most common pediatric liver malignancy, comprising
      approximately 1% of all pediatric cancers. The exact etiology of hepatoblastoma
      remains undetermined. Concerning hepatitis B infection, whether there are links
      with hepatoblastoma is poorly documented. Here, we summarize knowledge on the
      prevalence of hepatitis B seropositives among the patients with hepatoblastoma.
      According to the literature review, six reports were recruited for metanalysis,
      with a total of 60 cases. The overall prevalence of seropositive cancer was 3.3 %
      (2/560). Further analysis revealed no correlation between prevalence rate and
      nationality of the studied population (P > 0.05). Therefore, hepatitis B
      infection does not appear to be a contributing factor for hepatoblastoma. Further
      studies are needed to clarify which are the risk factors for the hepatoblastoma.

PMID- 16101337
TI  - Individuals with HGV-RNA are at high risk of B cell non-Hodgkin's lymphoma
      development.
AB  - Lymphoma is a common hematological malignancy. Hepatitis viruses, especially
      hepatitis B and hepatitis C, are known risk factors for development of non
      Hodgkin lymphomas. However, there are a number of patients with hepatitis in whom
      no virus can be identified and it was therefore postulated that there may be
      other agents which may be causing hepatitis. Many new hepatitis viruses have
      indeed been identified and proposed to have possible roles in pathogenesis of
      many disorders. Hepatitis G virus (HGV) is an example of a newly detected
      hepatitis virus. Whethere there is a correlation between infection and
      development of non-Hodgkin's lymphoma is of interest. Therefore an appraisal of
      the prevalence of HGV RNA among patients with B cell non-Hodgkin's lymphoma
      comparing with healthy control subjects was performed. According to the
      literature review, three reports covering 247 cases of non Hodgkin's lymphoma
      were recruited. The overall prevalence of HGV RNA positivity was found to be 7.2
      % (18/247). Of the three reports, only two had complete data on the prevalence in
      both patients with B cell non-Hodgkin's lymphoma and healthy control subjects
      andwere used for further metanalysis study, covering 178 cases and 355 healthy
      subjects. The overall antibody positive rate in the patients and healthy subjects
      were 8.4 % (15/178) and 0.8 % (3/355), respectively, with an odds ratio is 10.8.
      According to this study, it can be seen that individuals who are HGV RNA positive
      may be at very high risk of B cell non-Hodgkin's lymphoma development.

PMID- 16101338
TI  - Urinary bladder carcinoma and human papilloma virus infection, an appraisal of
      risk.
AB  - Human papilloma virus (HPV) is a well known risk factor for cancer development in
      different body sites, involved in the pathogenesis of several intraepithelial
      lesions and cancers, for example of the upper alimenatry and respiratory tracts
      and cervix. Urinary bladder carcinoma is a common urological malignancy for which
      a relationship with human HPV has been indicated, but the results are
      controversial. Here, the author performed an appraisal of the previous reports on
      the studies to document correlation between HPV infection, defined as DNA
      positive, and urinary bladder carcinoma. According to the literature review, 5
      reports were recruited for metanalysis, including 239 cases and 52 healthy
      subjects. The overall HPV DNA positive rates for the patients and healthy control
      subjects were 25.5 % (61/239) and 11.5 % (6/52), respectively, the odds ratio of
      2.6 pointing to potential as a risk factor.

PMID- 16101339
TI  - Cancer risk for Thai traffic police exposed to traffic benzene vapor.
AB  - Benzene exposure is of particular concern because recent research indicates that
      it can result in chronic toxicity, with an elevated risk of carcinogenesis.
      Exposure to benzene from automobile exhaust can be an important occupational
      problem for police. The present study was conducted to estimate risk of Thai
      traffic police developing cancer due to contact with traffic benzene vapor during
      daily work. According to the data obtained, the estimated predicted cancer
      incidence for traffic police is 0.05 case per 70-year period, simply translated
      as 1.8 cancer cases per 100,000 traffic police per year. This is clearly a cause
      of concern and annual check up and monitoring for benzene exposure among traffic
      police should be set up as part of a program for primary prevention of occupation
      -- related cancer.

PMID- 16101340
TI  - Assessing cancer burden in rural India: an analysis by cause of death statistics.
AB  - India lacks nationwide cancer registration and systematic death registration.
      Gaining insight into the magnitude of the cancer problem in India depends mainly
      on 14 population based cancer registries, which provide relatively accurate
      statistics although the area and population cover by these registries is minimal
      at about 7% (20% Urban and 1 % Rural). With estimation of cancer burden from
      other sources, paucity of adequate data on the one hand and the complex
      pathogenesis of disease on other makes for complexity in dealing with rural
      populations. However, surveys of cause of death do reveal some interesting
      patterns that may very well be of use for international comparisons. In this
      paper an attempt has been made to estimate the cancer burden in rural India using
      the information available from surveys of cause of death for rural populations
      conducted by the Government of India.

PMID- 16101341
TI  - Cancer and its prevention by some horticultural and field crops in Turkey.
AB  - Diet is considered to play an important role in the etiology of carcinogenesis,
      and almost 30 % of cancer development is known to have a dietary background. Many
      diets appear to contain groups of food components that can prevent, slow down, or
      even reverse carcinogenesis. In the present commentary, discussion is focused on
      the following crops: almonds, apricots, plums, peaches and nectarines, cherries,
      pears, figs, chestnuts, hazelnuts, pistachios, walnuts, grapes, strawberries,
      avocados, bananas, olives, lemons and limes, oranges (tangerines, mandarins,
      clemetines, satsuma), grapefruit and pomelons, artichokes, potatoes, green beans,
      carrots, cabbages, melons, watermelons, pumpkins, cucumbers, garlic, cauliflower,
      peppers, eggplants, tomatoes, onions, dry bean, soybeans, maize, barley, wheat,
      rye, and lentils. According to results some of epidemiology, numbers of
      horticultural and field crops of Turkey are likely to be associated with reduced
      risk of different cancers. Associations with protection in individual cases are
      here reviewed.

PMID- 16101342
TI  - How far should we promote smoking reduction in order to promote smoking
      cessation?
AB  - Smoking is the greatest preventable cause of death worldwide. In recent years
      considerable efforts have been devoted to reducing exposure to tobacco and
      related products. The ultimate aim has been to persuade people to stop smoking.
      It is generally recognized that smoking cessation is effective in reducing the
      burden of disease associated with smoking. However, smoking is an addiction to
      nicotine and relatively few people can quit successfully without professional
      help. Many do not want even to try. There is evidence that a reduction in
      cigarette consumption could result in improved health and provide an intermediate
      step before complete cessation, especially for those smokers who are not ready or
      willing to quit. Smoking reduction intervention with counselling and/or nicotine
      replacement therapy (NRT) have been shown by randomised controlled trials to be
      effective in reducing cigarette consumption for the general smoking population.
      We here present the argument that there may be a case for promoting smoking
      reduction both as a desirable goal in itself and as a first step towards smoking
      cessation.

PMID- 16101344
TI  - Development of a method for concentrating and purifying SARS coronavirus RNA by a
      magnetic bead capture system.
AB  - Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease
      caused by a novel coronavirus, which has been designated the SARS coronavirus
      (SARS-CoV). To date, molecular assays for the detection of SARS-CoV has focused
      mainly on reverse transcriptase-PCR (RT-PCR) analysis of specimens. However, RT
      PCR assays currently available have low sensitivity during the early stage of the
      disease in which the viral load in specimens is very low. A method for
      concentrating and purifying SARS-CoV RNA by a magnetic bead capture system was
      developed and followed by an RT-PCR assay in this study with the goal of
      improving the sensitivity of the RT-PCR method. This approach takes advantage of
      the cooperative interaction between adjacently hybridized oligonucleotides. A
      capture probe was covalently coupled to magnetic beads and a second probe, which
      anneals adjacent to the capture probe site, was prehybridized in solution to the
      target. It was shown that, when applied to SARS RNA samples, the sensitivity of
      nucleic acid capture RTPCR was about 10-fold greater than routine RT-PCR. This
      nucleic acid capture system was effective in improving the sensitivity of the RT
      PCR, due to enriching and purifying SARS-CoV RNA. The method will be helpful for
      the early detection of the SARS-associated coronavirus.

PMID- 16101345
TI  - Pathology of guinea pigs experimentally infected with a novel reovirus and
      coronavirus isolated from SARS patients.
AB  - Guinea pigs were inoculated with a reovirus (ReoV) and coronavirus (SARS-CoV)
      isolated from SARS patients to determine their potential role in the etiology of
      SARS. Animals infected with ReoV died between day 22 and day 30 postinoculation
      (PI) while 70% of the animals inoculated with ReoV and SARS-CoV died between day
      4 to day 7 PI. The titer of neutralizing antibodies against ReoV and SARS-CoV
      ranged from 80 to 160 when the animals were inoculated with the two viruses,
      respectively, while the titer of the antibodies was just below 10 in
      coinfections. The animal inoculated with ReoV developed diffuse alveolar damage
      similar to the exudative and leakage inflammation found in SARS patients, and was
      characterized by diffuse hemorrhage, fibroid exudation, hyaline membrane
      formation, and type II pneumocytes hyperplasia in alveolar interstitia. The
      pulmonary epithelial necrosis, excoriation, and early fibrosis of pulmonary
      tissue were only observed in ReoV-SARS-CoV groups and in SARS-CoV/ReoV groups.
      Other typical pathological changes included hemorrhagic necrosis in lymph nodes
      and spleen and hydropic degeneration in the liver. On the contrary, guinea pigs
      infected with SARS-CoV only developed interstitial pneumonitis. Our experiment
      demonstrate that ReoV might be one of the primary causes of SARS, since
      simultaneous coinfection can duplicate the typical pathological changes similar
      to that of SARS patients. This guinea pig model may provide a useful animal model
      for SARS.

PMID- 16101346
TI  - Experimental infection of macaques with the human reovirus BYD1 strain: an animal
      model for the study of the severe acute respiratory syndrome.
AB  - Experimental studies were performed to determine the role of a newly isolated
      reovirus (ReoV) from a severe acute respiratory syndrome (SARS) patient in the
      etiology of this newly described serious respiratory syndrome. Four cynomologus
      macaques were inoculated with this reovirus (BYD1) in an attempt to replicate the
      infection and pathology observed in SARS. The body temperature of the infected
      monkeys was monitored three times a day, and blood and fecal samples were
      periodically collected for specific immunology determinations. On days 7 and 33
      after inoculation, necropsies for pathological accessment and pathogen isolation
      were performed. The four infected macaques developed a fever on days 3 and 4
      after inoculation, and maintainted a febrile state for 4-6 days. The highest
      temperature in the animals recorded was 40.4 degrees C. After a recovery phase,
      the macaques developed a second febrile condition. Antibody titers against the
      reovirus injected by the intravenous route occurred in higher number than those
      in the nasal cavity. Four macaque monkeys demonstrated diffuse alveolar damage,
      characterized by hemorrhagic pneumonia, serosanguineous exudates, formation of
      hyaline membranes, and type II pneumocyte hyperplasia, which were similar to
      those that have been noted in SARS patients. Lymphocytes decreased in the cortex
      of the lymph node and in the white pulp of the spleen. ReoV was detected in
      pneumonic tissue by virus isolation and RT-PCR. The macaques infected with the
      newly isolated reovirus developed a fever, diffuse alveolar damage and pulmonary
      interstitial inflammation similar to that noted in SARS patients. This evidence
      demonstrates that ReoV might have a primary role in the etiology of SARS.

PMID- 16101347
TI  - Apoptosis induced by the SARS-associated coronavirus in Vero cells is replication
      dependent and involves caspase.
AB  - The pathogenesis of the severe acute respiratory syndrome (SARS), a newly
      emerging life-threatening disease in humans, remains unknown. It is believed that
      the modulation of apoptosis is relevant to diseases that are caused by various
      viruses. To examine potential apoptotic mechanisms related to SARS, we
      investigated features of apoptosis induced by the SARS-associated coronavirus
      (SARS-CoV) in host cells. The results indicated that the SARS-CoV-induced
      apoptosis in Vero cells in a virus replication-dependent manner. Additionally,
      the downregulation of Bcl-2, the activation of casapse 3, as well as the
      upregulation of Bax were detected, suggesting the involvement of the caspase
      family and the activation of the mitochondrial signaling pathway. Although there
      is a positive correlation between apoptosis and virus replication, the latter is
      not significantly blocked by treatment with the caspase inhibitor z-DEVD-FMK.
      These preliminary data provide important information on both the pathogenesis and
      potential antiviral targets of SARS-CoV.

PMID- 16101348
TI  - Identification and antigenic epitope mapping of immunodominant region amino
      residues 510 to 672 on the spike protein of the severe acute respiratory syndrome
      coronavirus.
AB  - The severe acute respiratory syndrome (SARS) is a newly emerging human infectious
      disease caused by the severe acute respiratory syndrome coronavirus (SARS-CoV).
      The spike (S) protein of SARS-CoV is a major virion structural protein. It plays
      an important role in the interaction with receptors and neutralizing antibodies.
      In this study, the S1 domain of the spike protein and three truncated fragments
      were expressed by fusion with GST in a pGEX-6p-1 vector. Western blot results
      demonstrated that the 510-672 fragment of the S1 domain is a linear epitope
      dominant region. To map the antigenic epitope of this linear epitope dominant
      region, a set of 16 partially overlapping fragments spanning the fragment were
      fused with GST and expressed. Four antigenic epitopes S1C3 (539-559), S1C4 (548
      567), S1C7/8 (583-606), and S1C10/11 (607-630) were identified. Immunization of
      mice with each of the four antigenic epitope-fused proteins revealed that all
      four proteins could elicit spike protein specific antisera. All of them were able
      to bind to the surface domain of the whole spike protein expressed by recombinant
      baculovirus in insect cells. Identification of antigenic epitopes of the spike
      protein of SARS-CoV may provide the basis for the development of immunity-based
      prophylactic, therapeutic, and diagnostic clinical techniques for the severe
      acute respiratory syndrome.

PMID- 16101349
TI  - Elicitation of immunity in mice after immunization with the S2 subunit of the
      severe acute respiratory syndrome coronavirus.
AB  - The S2 domain of the severe acute respiratory syndrome coronavirus (SARS-CoV)
      spike (S) protein is responsible for fusion between virus and target cell
      membranes, and is expected to be immungenic. In this study, we investigated the
      immune responses against the S2 subunit in BALB/c mice, which were vaccinated
      either with plasmid DNA encoding the S2 domain (residues 681-1120), the
      recombinant S2 fragment (residues 681-980) in incomplete Freund's adjuvant, or
      with inactivated SARS-CoV. The increased number of specific cytotoxic cells
      (CTLs) and the high titer of specific antibody showed stimulation of both arms of
      the immune system in these groups. The shift in cytokines suggested that Th1
      polarized immune response was induced by plasmid pCoVS2, meanwhile the Th2
      dominant response was induced by recombinant S2 fragment and inactivated vaccine.
      However, the titer of neutralizing antibodies was only detectable in mice
      immunized with inactivated virus, but not with pCoVS2 plasmid. Taken together,
      the S2 domain could induce specific cellular immune response and a high level of
      total IgG but little neutralizing antibodies against infection by SARSCoV.

PMID- 16101350
TI  - Construction of a eukaryotic expression plasmid encoding partial S gene fragments
      of the SARS-CoV and its potential utility as a DNA vaccine.
AB  - The spike (S) protein, a main surface antigen of the SARS coronavirus (SARS-CoV),
      is considered to be one of the most important protective antigen candidates for
      targets for vaccine design against the virus. In this study, a secreted
      recombinant expression plasmid, pVAX-S1, encoding the partial S protein with a
      signal peptide, was constructed and used to immunize BALB/c mice through
      electroporation. It was demonstrated that the eukaryotic expression vector pVAX
      S1 was successfully constructed by restriction enzyme and sequence analysis. The
      expressed protein could be detected specifically by Western blot analysis. The
      serum IgG level of the vaccine group mice was significantly higher than that of
      the corresponding control group at day 14 after vaccination (P < 0.05). The
      vaccine group demonstrated significantly higher S1 protein lymphocyte
      proliferation index (LPI) than the control groups (P < 0.05). Furthermore, in the
      experimental group, a decrease in the ratio of CD4(+) to CD8(+) T-lymphocytes and
      an increase level of IFN-gamma in serum were observed. However, interleukin-4 (IL
      4) was not detectable in two groups. These results strongly demonstrated that the
      pVAX-S1 plasmid could induce humoral and cellular immune responses in mice, and
      may be a potential candidate for a DNA vaccine against the SARS coronavirus.

PMID- 16101352
TI  - FDA report.

PMID- 16101351
TI  - Profiles of IgG antibodies to nucleocapsid and spike proteins of the SARS
      associated coronavirus in SARS patients.
AB  - To evaluate humoral immunity against the SARS-associated coronavirus (SARS-CoV),
      we studied the profiles of IgG antibodies to the nucleocapsid (N) and spike (S)
      proteins of SARS-CoV. Serum specimens from 10 SARS patients were analyzed by
      Western blotting and an enzyme-linked immunosorbent assay (ELISA) using purified
      recombinant N and truncated S (S1, S2, and S3) proteins as antigens. Western
      blotting results demonstrated that 100% of the SARS patients tested positive for
      N protein-specific antibodies, 50% for S1 protein-specific antibodies, 30% for S2
      protein-specific antibodies, and 70% for S3 protein-specific antibodies. The
      ELISA results, which showed positive rates of IgG reactivity against recombinant
      proteins N, S1, S2, and S3, were, respectively, 28.57, 14.29, 14.29, and 14.29%
      at week 1, 77.78, 55.56, 44.44, and 66.67% at week 2, 100, 75, 75, and 87.5% at
      week 3, and 100, 77.78, 77.78, and 88.89% after 3 weeks. The average titers of
      IgG against recombinant proteins N, S1, S2, and S3 were, respectively, 691, 56,
      38, and 84 after 3 weeks. These results suggest that the recombinant proteins N
      and S3 are potentially useful antigens for a serological diagnosis of SARS. In
      consideration of possible cross-reactivity among N proteins of SARS-CoV and other
      coronaviruses, immunoassays using recombinant N protein in combination with S3 as
      antigens might improve the specificity of SARS diagnoses.

PMID- 16101353
TI  - Impact of local adjuncts to scaling and root planing in periodontal disease
      therapy: a systematic review.
AB  - BACKGROUND: Chronic periodontitis affects many adults in the United States, some
      severely enough to threaten tooth loss. Of particular clinical importance is
      whether scaling and root planing (SRP) accompanied by a local adjunctive
      therapeutic agent improves outcomes over time compared to SRP alone. The
      adjunctive therapeutic agents investigated include: tetracycline, minocycline,
      metronidazole, a group of other antibiotics, chlorhexidine, and a group of
      antimicrobials. Primary outcomes considered are reductions in probing depth (PD)
      and gains in clinical attachment level (CAL). METHODS: RTI-UNC Evidence-Based
      Practice Center staff searched MEDLINE (1966 through December 2002) and EMBASE
      (through February 2002) to identify clinical trials published in English that 1)
      involved adults with chronic periodontitis but no serious comorbidities; 2)
      tested one or more chemical antimicrobial agents as an adjunct to SRP alone or
      with a placebo; 3) had a concurrent control group that received the same SRP as
      the treatment group; 4) reported outcomes for specified, fixed time periods; and
      5) if multiple antimicrobials were tested, reported outcomes for each agent
      separately. We performed qualitative analyses and meta-analyses of PD and CAL
      effect sizes when the necessary data were available from at least three studies
      at 6-month follow-up. RESULTS: Among the locally administered adjunctive
      antimicrobials, the most positive results occurred for tetracycline, minocycline,
      metronidazole, and chlorhexidine. Adjunctive local therapy generally reduced PD
      levels. Differences between treatment and SRP-only groups in the baseline-to
      follow-up period typically favored treatment groups but usually only modestly
      (e.g., from about 0.1 mm to nearly 0.5 mm) even when the differences were
      statistically significant. Effects for CAL gains were smaller and statistical
      significance less common. The marginal improvements in PD and CAL were a fraction
      of the improvement from SRP alone. CONCLUSIONS: Whether such improvements, even
      if statistically significant, are clinically meaningful remains a question. A
      substantial agenda of future research to address this and other issues (e.g.,
      costs, patient-oriented outcomes) is suggested.

PMID- 16101354
TI  - Sinus floor elevation using osteotomes: a systematic review and meta-analysis.
AB  - BACKGROUND: Various techniques of sinus floor elevation (SFE) are described. The
      elevation with osteotomes (OSFE) from a crestal approach is a relatively new
      technique. The aim of this systematic review and meta-analysis was to evaluate
      the clinical outcome of implants placed into the maxillary sinus augmented with
      an OSFE technique. METHODS: A systematic online and manual review of the
      literature identified articles dealing with OSFE. Applying rigid inclusion
      criteria, screening and data abstraction were performed independently by two
      reviewers. The follow-up of loaded implants was a minimum of 6 months. The
      identified articles were analyzed regarding implant outcome and defined surgical
      aspects. Survival and success rates were estimated by Kaplan-Meier curves.
      RESULTS: Eight out of 44 articles dealing with osteotome sinus floor elevation
      met the inclusion criteria. Five of the studies met established success criteria.
      The survival and success rates were 95.7% and 96.0% after 24 months and 36
      months, respectively. The median and mean follow-up periods were 24 and 18.73
      months for the survival rate and 24 and 19.7 months for the success rate.
      Regarding different surgical elements, i.e., osteotome techniques, implant types,
      and augmentation materials, the database was multivariate. Thus, no statistical
      analysis could be performed on these parameters. CONCLUSIONS: Short-term clinical
      success/survival (<or years) of implants placed with an osteotome sinus floor
      elevation technique seems to be similar to that of implants conventionally placed
      in the partially edentulous maxilla. Controlled prospective clinical studies are
      needed to evaluate the long-term outcome and various surgical modifications of
      OSFE.

PMID- 16101355
TI  - Does loading time affect implant survival? A meta-analysis of 1,266 implants.
AB  - BACKGROUND: Considerable controversy exists as to whether immediate or early
      implant loading is associated with a higher failure rate compared to conventional
      loading. Numerous trials conducted have yielded inconsistent results, partly due
      to low statistical power. Thus, we sought to determine whether combining results
      from all published trials would provide a better estimate of the impact of
      implant loading time on survival. METHODS: We carried out a meta-analysis of all
      previously published prospective trials comparing conventional with early or
      immediate implant loading. The outcome of interest was implant failure rate. The
      Q statistics test was used to assess the presence of heterogeneity. We identified
      relevant studies through a search of the MEDLINE database and the Cochrane
      Registry of Controlled Trials. RESULTS: We found 13 prospective trials (1,266
      implants) in which early or immediate implant loading was compared to
      conventional loading. Overall there was no difference in implant failure rate
      between loading techniques (odds ratio [OR] 0.91; 95% CI: 0.41 to 2.03; P=0.41).
      Implant failure occurred slightly, although not statistically significant, less
      often with early implant loading (OR 0.52; 95% CI: 0.22 to 1.24; P=0.07).
      Immediate implant loading was associated with slightly, although not
      statistically significant, worse outcomes (OR 1.26; 95% CI: 0.38 to 4.13;
      P=0.35). Pooling of randomized controlled trials (RCTs) confirmed these results.
      CONCLUSIONS: In a meta-analysis of 13 prospective trials, early implant loading
      was not associated with worse outcomes compared to conventional loading. Further
      evaluations in adequately powered large prospective trials are needed to confirm
      these findings.

PMID- 16101356
TI  - Cyclosporin-induced gingival overgrowth: a clinical-epidemiological evaluation of
      121 Italian renal transplant recipients.
AB  - BACKGROUND: Although other immunosuppressive agents have been recently introduced
      (e.g., tacrolimus), it has been calculated that in the next decade about 1
      million people will still be taking cyclosporin (CsA). The association between
      gingival overgrowth (GO) and the use of CsA is still not clear. In the present
      study we evaluated the prevalence and the degree of GO in a group of Italian
      renal transplant patients and the possible relationship between gingival lesions
      and demographic, oral, systemic, and pharmacological variables. METHODS: One
      hundred twenty-one renal transplant recipients receiving immunosuppressive
      therapy with CsA were evaluated in this study. Patients were classified in two
      groups. In the first (screening group), we included all those patients referred
      by the Parma University Renal Transplant Center for a general oral checkup, with
      no specific indications for GO. The second group (non-screening group) included
      all those patients who specifically had been referred to the Oral Pathology and
      Oral Medicine Unit because of GO. We considered the following variables: gender,
      daily CsA dose, duration of immunosuppressive treatment, CsA plasma
      concentration, concomitant use of another immunosuppressive agent (azathioprine),
      use of other GO inducers (calcium channel blockers, anti-epileptic drugs), oral
      hygiene scores, and other drugs taken at the time of oral examination. RESULTS:
      Fisher's exact test and chi square test demonstrated that in the screening group,
      duration of immunosuppressive treatment and oral hygiene scores were associated
      both with the prevalence and the high GO scores (P (1) (DIT) <0.0001; P (2)
      (DIT)=0.0023; P (1) (hyg)=0.0084; P (2) (hyg)=0.0068). In the screening group,
      concomitant use of CsA and azathioprine is related to a low development degree of
      GO (P=0.0088). In the non-screening group, we found a significant association
      between poor oral hygiene and high degree of GO (P=0.0349). CONCLUSION: In
      addition to a probable genetic predisposition, duration of immunosuppressive
      treatment and oral hygiene status are the most important variables related to
      development and degree of GO during the use of CsA in this study.

PMID- 16101357
TI  - Inhibition of growth of human gingival fibroblasts by chimeric DNA-RNA hammerhead
      ribozyme targeting transforming growth factor-beta 1.
AB  - BACKGROUND: Transforming growth factor (TGF)-beta1 is involved in the
      pathogenesis of both drug-induced gingival overgrowth and hereditary gingival
      fibromatosis. Ribozymes enzymatically cleave target mRNAs and are expected to be
      utilized as the basis of novel nucleic acid-based therapies. We designed a
      chimeric DNA-RNA ribozyme targeting TGF-beta1 mRNA and examined its effect on
      growth of gingival fibroblasts in culture. METHODS: Chimeric DNA-RNA hammerhead
      ribozyme with sequence complementary to the loop structure of human TGF-beta1
      mRNA was used. We evaluated transfer of the chimeric ribozyme by hemagglutinating
      virus of Japan (HVJ)-envelope into cultured human gingival fibroblasts in vitro
      and rat gingival tissues in vivo. We then examined effects of the chimeric
      ribozyme to TGF-beta1 on proliferation and DNA synthesis in human gingival
      fibroblasts. We also examined effects of the chimeric ribozyme to TGF-beta1 on
      expression of TGF-beta1, type IV collagens, and fibronectin mRNAs and expression
      of TGF-beta1 protein in human gingival fibroblasts. RESULTS: Chimeric ribozyme
      was sufficiently distributed into human fibroblasts in vitro and rat gingivae in
      vivo. Chimeric ribozyme to TGF-beta1 significantly inhibited expression of TGF
      beta1, type IV collagen, and fibronectin mRNAs and TGF-beta1 protein in human
      gingival fibroblasts. Mismatch ribozyme had no effect on expression of these
      molecules. Chimeric ribozyme to TGF-beta1 also significantly inhibited
      proliferation and DNA synthesis in gingival fibroblasts. CONCLUSION: Chimeric DNA
      RNA ribozyme targeting TGF-beta1 may be a useful gene therapy agent for treatment
      of gingival hyperplasia.

PMID- 16101358
TI  - Comparative study between the effects of photodynamic therapy and conventional
      therapy on microbial reduction in ligature-induced peri-implantitis in dogs.
AB  - BACKGROUND: Progressive peri-implant bone losses, which are accompanied by
      inflammatory lesions in the soft tissues, are referred to as peri-implantitis.
      The aim of this study was to compare the effects of photodynamic therapy (PDT)
      and conventional technique on microbial reduction in ligature-induced peri
      implantitis in dogs. METHODS: Eighteen third premolars from nine Labrador
      retriever dogs were extracted and the implants were submerged. After
      osseointegration, peri-implantitis was induced. After 4 months, ligature was
      removed and natural bacterial plaque was allowed to form for another 4 months.
      The animals were then randomly divided into two groups. In the conventional
      group, they were treated using mucoperiosteal flaps for scaling the implant
      surface and chlorexidine (conventional) irrigation. In the PDT group, only
      mucoperiosteal scaling was carried out before photodynamic therapy. Inside the
      peri-implant pocket, a paste-based azulene photosensitizer was placed and then a
      GaAlAs low-power laser (lambda=660 nm, P=40 mW, E=7.2 J for 3 minutes) was used.
      Microbiological samples were obtained before and immediately after treatment.
      Before treatment, one implant was removed and analyzed by scanning electron
      microscopy to validate the contamination. RESULTS: The results of this study
      showed that Prevotella sp., Fusobacterium sp., and S. Beta-haemolyticus were
      significantly reduced for both groups. After treatment, no significant
      differences were observed between the groups. CONCLUSION: These findings suggest
      that photodynamic therapy is a non-invasive method that could be used to reduce
      microorganisms in peri-implantitis.

PMID- 16101359
TI  - Three-dimensional quantification of alveolar bone loss in Porphyromonas
      gingivalis-infected mice using micro-computed tomography.
AB  - BACKGROUND: Animal models are routinely used for the study of the pathogenesis of
      periodontal disease. However, some of the methods used for evaluating alveolar
      bone loss are limited to linear or two dimension measurements, while other
      methods, such as histology, are labor consuming. The present study was designed
      to evaluate a novel method for assessing the volume of alveolar bone loss in mice
      and to compare it to the traditional morphometric (linear) technique. METHODS:
      Seven- to 8-week-old BALB/c mice were divided into three equal groups of six
      each; two groups were infected orally with Porphyromonas gingivalis (P.
      gingivalis) 381 or 53,977, while the third group was used as non-infected
      control. Forty-two days following infection, serum samples were obtained and
      maxillae were harvested. Bone loss was evaluated by micro-computed tomography
      (micro-CT) and by the morphometric technique. RESULTS: Significant decrease in
      residual supportive bone volumes (RSBV) was observed in both P. gingivalis
      infected groups compared to the control group (P<0.0001). The P. gingivalis
      53,977-infected group showed less residual supportive bone volume compared to the
      P. gingivalis 381-infected group, but there were no significant differences
      between these two groups. Using the morphometric technique, the differences
      between the three groups were not found to be statistically significant (P>0.05).
      CONCLUSIONS: The present study describes a novel micro-CT technique for
      volumetric evaluation of alveolar bone loss in mice. This technique is relatively
      simple and accurate, and due to its high sensitivity, enables the investigator to
      reduce the number of animals needed in each experimental group.

PMID- 16101360
TI  - Analysis of rat calvaria defects implanted with a platelet-rich plasma
      preparation: radiographic observations.
AB  - BACKGROUND: Platelet-rich plasma (PRP) harbors growth factors identified in bone.
      It has been suggested that these factors enhance osteogenesis. The objective of
      this study was to conduct a radiographic evaluation on local bone formation
      following surgical implantation of a PRP preparation using a critical-size rat
      calvaria defect model. METHODS: Thirty 22-week-old male Sprague-Dawley rats were
      used. The PRP preparation was obtained from 10 ml of whole blood drawn from one
      age-matched donor rat. The preparation was processed by gradient density
      centrifugation and stored at -80 degrees C until use. Using aseptic techniques,
      the PRP preparation soak-loaded onto an absorbable collagen sponge (ACS) carrier
      or ACS alone was surgically implanted into contralateral critical-size 6 mm rat
      calvaria osteotomies in 18 animals. Twelve animals received ACS alone versus sham
      surgery in contralateral defects. Animals were sacrificed at 4 and 8 weeks when
      biopsies were collected and radiographs were obtained using a standardized
      protocol. Three masked examiners independently evaluated the radiographic images
      of the defect sites. Examiner reproducibility was examined by repeat evaluation
      of all defect sites (r=0.6; P <0.0001). RESULTS: The animals were maintained
      without adverse events. Defect sites in two animals receiving ACS versus sham
      surgery (4-week healing interval) were not evaluated due to specimen damage.
      Seventy-five percent of the sites (PRP/ACS or ACS) exhibited partial closure at 4
      weeks; one site (ACS) exhibited full closure without significant differences
      between protocols (P=0.1797). Fifty percent of the sites receiving PRP/ACS
      exhibited full closure and 20% partial closure at 8 weeks versus 20% and 80%,
      respectively, for the ACS control (P=0.7532). There were no noteworthy
      differences between sites receiving ACS versus sham surgery at 4 or 8 weeks.
      CONCLUSION: The results suggest that the PRP preparation does not have a
      significant effect on osteogenesis.

PMID- 16101361
TI  - Differential induction of human beta-defensin expression by periodontal
      commensals and pathogens in periodontal pocket epithelial cells.
AB  - BACKGROUND: To investigate the possible role of beta-defensins in gingival health
      and periodontal disease, we examined the effect of several stimuli on the
      expression of interleukin-8 (IL-8), human beta-defensin-1, -2, -3, and -4 (hBD)
      in primary human diseased gingival epithelial (HGE) cell cultures from
      periodontitis patients by quantitative TaqMan reverse transcription polymerase
      chain reaction (RT-PCR). METHODS: Several strains of the periodontopathogens
      Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were added to
      the cells, as well as the oral commensal bacteria Fusobacterium nucleatum and
      Escherichia coli. The induction by the proinflammatory stimuli phorbol 12
      myristate 13-acetate (PMA) and tumor necrosis factor-alpha (TNF-alpha) was also
      tested. RESULTS: In addition to the published observations (PMA induces hBD-2 and
      -4; TNF-alpha induces hBD-2 and -3), it was found that PMA can upregulate hBD-1
      and hBD-3, whereas TNF-alpha can induce hBD-4. The commensal bacteria were
      significant inducers of hBD-2, hBD-3, and IL-8. The pathogen P. gingivalis
      induced hBD-1 and hBD-3 at different time points than the commensals, but no
      induction of IL-8 and hBD-2 could be observed. These data fit with the chemokine
      paralysis theory. A correlation was found between the pathogenicity of different
      serotypes of A. actinomycetemcomitans and the induction profiles of defensins and
      IL-8. CONCLUSION: The results suggest that a correlation can be found in diseased
      oral epithelium between the defensin profiles that are induced and the
      pathogenicity of the oral bacterial strains.

PMID- 16101362
TI  - The influence of surgical treatment of periodontal disease on selected lymphocyte
      subpopulations important for cellular and humoral immune responses.
AB  - BACKGROUND: Periodontal disease is a complex pathological process involving a
      wide spectrum of immunological reactions. The aim of the study was to evaluate
      the influence of surgical periodontal treatments on peripheral blood lymphocyte
      subpopulations. METHODS: The study was performed in 40 generally healthy
      individuals diagnosed with generalized chronic periodontitis and a control group
      of 36 persons without periodontitis. Peripheral blood lymphocyte subpopulations
      were examined in both groups. Periodontal treatment was performed, using four
      different surgical procedures, in the study group. Peripheral blood lymphocyte
      subpopulations were re-evaluated again after 6 months. RESULTS: Periodontal
      treatment resulted in a significant improvement of all measured clinical
      parameters, regardless of the surgical procedure. When evaluated in the study
      group as a whole, percentages of all but CD8+ T lymphocyte subpopulations were
      significantly different from the control group at baseline. Values in both groups
      after treatment were similar. Correlation analysis suggests a connection between
      the presence of CD25+ cells and selected clinical parameters of periodontal
      disease (probing depth and clinical attachment loss). CONCLUSIONS: Statistically
      significant differences in the percentages of selected lymphocyte subpopulations
      in the peripheral blood of patients and healthy controls were found. The results
      suggest a correlation between selected clinical periodontal parameters and
      percentage of activated cells expressing the interleukin (IL)-2 receptor.
      Periodontal treatment resulted in significant improvement in the measured
      clinical and immunological parameters. It seems that the type of surgical
      treatment has little effect on the normalization of quantitative disturbances of
      the examined peripheral blood lymphocytes.

PMID- 16101363
TI  - Non-invasive method to measure the length of soft tissue from the top of the
      papilla to the crestal bone.
AB  - BACKGROUND: In order to verify the results of interdental papilla regeneration,
      various methods of measuring the length of the papilla have been introduced.
      Invasive methods, such as bone probing under local anesthesia, might cause
      discomfort to the patients and possibly damage the delicate gingival unit. The
      purpose of the present study was to validate a method of measuring the length of
      the interdental papilla non-invasively, using radiopaque material and a
      periapical radiograph. METHODS: This study involved 142 interproximal papillae in
      40 patients with chronic periodontitis. The distance between the radiopaque
      material and most coronal portion of the crestal bone was measured (radiographic
      length of papilla, RL). Bone probing at the interdental papilla was performed
      after local anesthesia (bone probing length, BPL). After flap elevation, the
      actual length of the papilla was measured (actual length of papilla, AL). A
      correlation analysis was performed between AL-RL and AL-BPL using Pearson's
      correlation coefficients. RESULTS: The correlation between AL-RL and AL-BPL was
      0.903 and 0.931, respectively, both of which showed significance at the 0.01
      level. CONCLUSION: The results of this study suggest that the noninvasive method
      using a radiopaque material and periapical radiograph could be utilized to
      measure the length of the interdental papilla.

PMID- 16101364
TI  - Influence of nicotine and cotinine on epithelial colonization by
      periodontopathogens.
AB  - BACKGROUND: Since smoking is an established risk factor for the development of
      periodontitis, the present study investigated whether nicotine and cotinine can
      make epithelial cells more prone to colonization by periodontopathogens. METHODS:
      Primary epithelial cell mono-layers were inoculated with nicotine and cotinine
      prior to adhesion experiments with Actinobacillus actinomycetemcomitans and
      Porphyromonas gingivalis. The number of bacteria associated with cells inoculated
      or not with nicotine or cotinine were assessed by an indirect culture viability
      assay. The same experimental set-up was used for assessing HeLa cells exposed to
      cigarette smoke extract (CSE). RESULTS: Primary epithelial cells inoculated with
      concentrations of nicotine and cotinine, found in smokers and non smokers, did
      not show significant differences (P>0.05) in colonization susceptibility to A.
      actinomycetemcomitans. When these concentrations were increased to 1 mg/ml, a
      significant (P<0.05) and species-specific effect of the colonization
      susceptibility of epithelial cells was observed: It increased for A.
      actinomycetemcomitans, while it decreased for P. gingivalis. For both species the
      effects were more pronounced for nicotine, although this was not statistically
      significant. The change in colonization susceptibility did not result from
      alterations of the bacterial viability due to nicotine or cotinine. Treatment of
      HeLa cells with CSE also led to a species-specific variation in colonization
      tendency; i.e., increased for A. actinomycetemcomitans (P<0.05), but not for P.
      gingivalis. CONCLUSIONS: The susceptibility of epithelial cells to become
      colonized by either A. actinomycetemcomitans or P. gingivalis could be altered by
      nicotine, cotinine, or CSE in a time-dependent, species-specific manner. Whether
      these findings that support the hypothesis of an increased patient susceptibility
      for bacterial adhesion to epithelial cells in smokers are clinically relevant
      remains to be proven.

PMID- 16101365
TI  - A 2-year follow-up of root coverage using sub-pedicle acellular dermal matrix
      allografts and subepithelial connective tissue autografts.
AB  - BACKGROUND: Coverage of roots exposed by gingival recession is one of the main
      objectives of periodontal reconstructive surgery. A large variety of mucogingival
      grafting procedures are available. However, the long-term effectiveness of this
      procedure is still not clear. This study compared the effectiveness of sub
      pedicle acellular dermal matrix allografts with subepithelial connective tissue
      autografts in achieving root coverage 2 years postoperatively. METHODS: One
      hundred one (101) patients were treated with dermal matrix allografts (mean age,
      28.4+/- 0.7 years; mean recession, 4.2 mm) and 65 patients treated with
      connective tissue graft (mean age, 30.1+/- 1.4 years; mean recession, 4.9 mm).
      All patients underwent full periodontal evaluation and presurgical preparation,
      including oral hygiene instruction and scaling and root planing. The exposed
      roots were thoroughly planed and covered by a graft without any further root
      treatment or conditioning. There were no differences in the average age, time of
      follow-up, or gender between the two groups. Patients were evaluated periodically
      between 1 and 2 years. Residual recession and defect coverage were assessed.
      RESULTS: Mean residual root recession after root coverage with acellular dermal
      matrix allograft was 0.2 +/- 0.04 mm, with defect coverage of 95.9% +/- 0.9%.
      Frequency of defect coverage was 82.2%. Root coverage was 98.8% +/- 0.2%,
      resulting in a frequency of root coverage of 100%. Gain in keratinized gingiva
      was 2.2+/- 0.04 mm and attachment gain was 4.5+/- 0.1 mm per patient. Connective
      tissue autografts resulted in mean residual root recession of 0.1+/- 0.04 mm,
      with percent defect coverage of 97.8%+/- 0.6% and frequency of defect coverage of
      95.4%. Root coverage was 99.1%+/- 0.2%, and frequency of root coverage was 100%.
      Gain in keratinized gingiva was 3.0+/- 0.1 mm and attachment gain was 5.3+/- 0.2
      mm per patient. No significant differences in final recession and root coverage
      between the two treatment methods were found. However, autografts resulted in
      significant increases in defect coverage, keratinized gingival gain, attachment
      gain, and residual probing depth. The clinical results were stable for the 2-year
      follow-up period. CONCLUSIONS: These results indicate that coverage of root by
      sub-pedicle acellular dermal matrix allografts or subepithelial connective tissue
      autografts is a very predictable procedure which is stable for 2 years
      postoperatively. However, subepithelial connective tissue autografts resulted in
      significant increases in defect coverage, keratinized gingival gain, attachment
      gain, and residual probing depth.

PMID- 16101366
TI  - Lupinus albus, a novel vegetable extract with metalloproteinase inhibitory
      properties: a potential periodontal therapy.
AB  - BACKGROUND: In this study we examine the properties of a vegetable extract from
      seeds of Lupinus albus (LU 105). In previous works we demonstrated that LU 105
      reduced the expression, by gingival fibroblasts, of both matrix metalloproteinase
      (MMP)-2 and MMP-9. We decided to study the impact of LU 105 on cell proliferation
      and morphology. Using organ culture media we also studied the MMP and tissue
      inhibitors of metalloproteinases (timp) expression AND THE cytokines secretion.
      METHODS: Healthy and inflamed gingival biopsies were placed in appendage culture
      with or without LU 105. The organ culture media were analyzed using Western
      blottings (MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, TIMP-1, and TIMP-2) and
      gelatine zymography. A reverse transcription polymerase chain reaction (RT-PCR)
      was also performed on healthy and inflamed gingival biopsies, which were
      maintained in culture with or without LU 105 0.1%. Then, we decided to determine
      the amount of cytokines present in the organ culture media such as interleukin
      (IL)-1 beta, IL-4, IL-6, transforming growth factor (TGF)-beta, and tumor
      necrosis factor (TNF)-alpha. RESULTS: When gingival biopsies derived from
      inflamed tissues were cultured with LU 105 0.1% in the culture media, the MMP and
      TIMP expression and activity decreased significantly when compared to cultures
      without LU 105. Moreover, we did not note any statistical difference in the cell
      proliferation compared with human gingival fibroblast cultures without LU 105.
      Furthermore, IL-1 beta, IL-6, TGF-beta, and TNF-alpha amounts in the culture
      media decreased significantly, whereas IL-4 increased significantly when LU 105
      0.1% was added to the culture media. CONCLUSION: LU 105, a novel
      metalloproteinase inhibitor with few consequences on cell proliferation and
      morphology, is a vegetable extract with potential clinical capacity.

PMID- 16101367
TI  - Microvascular response in the periosteum following mucoperiosteal flap surgery in
      dogs: 3-dimensional observation of an angiogenic process.
AB  - BACKGROUND: An increase in blood flow from the periosteum after mucoperiosteal
      flap surgery is essential for healing and angiogenesis and repair may work in
      close cooperation to facilitate this process. To investigate the role of the
      periosteal vascular plexus in the healing process, we used 3-dimensional (3-D)
      and ultrastructural monitoring of the angiogenic process after elevation of the
      mucoperiosteal flap. METHODS: Mucoperiosteal flap surgery was performed on nine
      adult beagle dogs. The periosteal vascular plexus was observed 3, 5, and 7 days
      after surgery in histological specimens in which blood vessels were injected with
      India ink under a light microscope, in ultrathin sections under a transmission
      electron microscope, and in acryl plastic vascular cast specimens under a
      scanning electron microscope. RESULTS: On day 3 after surgery, new blood vessels,
      formed through sprouting, bridging, and intussusception, were observed in
      ultrathin sections and vascular casts. In addition, blood island-like structures
      consisting of clustered immature endothelial cells were noted in the repaired
      tissue. On days 5 to 7 after surgery, 3-D observation of vascular casts clarified
      that these new blood vessels had a sinus-like morphology in the interstitium of
      the periosteal vascular plexus. These new sinusoidal vessels exhibited a
      stereoscopic structure with increased continuity as the blood vessels matured and
      ultrastructurally the vascular endothelium was thinned. CONCLUSIONS: After
      mucoperiosteal flap elevation, the periosteal vasculature exhibited potent blood
      vessel-forming activity through various angiogenic mechanisms and through repair
      activity. Our results provide a 3-dimensional clarification that the periosteal
      vascular plexus has an important role in the healing process after flap surgery.

PMID- 16101368
TI  - Microvascular response in the periosteum following mucoperiosteal flap surgery in
      dogs: angiogenesis and bone resorption and formation.
AB  - BACKGROUND: When surgical stress reaches the periosteum, bone resorption and
      formation that occur as a periosteal response are closely related to angiogenesis
      and hemodynamics. Thus, we investigated bone remodeling in the healing process
      after mucoperiosteal flap surgery, focusing our attention on the
      microcirculation. METHODS: Mucoperiosteal flap surgery was performed on 12 adult
      beagle dogs. The periosteal vascular plexus was observed on days 7, 14, 21, and
      28 after surgery, using three different techniques: in histological specimens
      into which India ink was injected into blood vessels, under a light microscope;
      in ultrathin sections, using a transmission electron microscope; and in acryl
      plastic-injected vascular corrosion cast specimens, under a scanning electron
      microscope. RESULTS: On day 7 after surgery, the interstitum of the elevated
      mucoperiosteal vascular plexus was filled with sinusoidal new blood vessels. Bone
      resorption by osteoclasts was observed around these new blood vessels and many
      highly permeable fenestrations were present in the vascular endothelium. On day
      14 after surgery, sinusoidal new blood vessels were more markedly developed and
      some regions exhibited glomeruluslike morphology consistent with bone resorption
      cavities. Activated osteoblasts were present around these new blood vessels and
      highly permeable vesicles, which were considered to be possible vesiclo-vacuolar
      organelles (VVOs) and caveolae, were noted in the vascular endothelium. On days
      21 and 28 after surgery, the mucoperiosteal vascular plexus was dissected through
      regression of endothelial cells and fibroblasts and reconstructed into a rough
      mesh structure, and simultaneously the bone surface became smooth. CONCLUSION:
      The morphology of the mucoperiosteal vascular plexus changed with bone metabolism
      and these changes contributed to transport of substances involved in periodontal
      repair.

PMID- 16101369
TI  - Treatment of wide, shallow, and predominantly 1-wall intrabony defects with a
      bioabsorbable membrane: a randomized controlled clinical trial.
AB  - BACKGROUND: The regenerative therapy of non-contained intrabony defects achieves
      better results when bioabsorbable membranes are combined with a filling material.
      The purpose of the present study was to analyze clinical and radiographic
      effectiveness of a space-making bioabsorbable membrane in the treatment of wide
      and shallow intrabony defects characterized by a relevant 1-wall component.
      METHODS: Eighteen pairs of angular bone defects were selected in 18 healthy, non
      smoking patients (age range 30 to 66 years). Prior to the surgical phase,
      patients were enrolled in a strict periodontal program including oral hygiene
      instructions and scaling and root planing (presurgical full-mouth plaque score
      <10%). Using a split-mouth design, 18 sites were randomly assigned to receive
      guided tissue regeneration (GTR) using a bioabsorbable membrane (test group) and
      18 to receive open flap debridement alone (control group). Clinical treatment
      outcome was evaluated 12 months postoperatively for changes in probing depth
      (PD), clinical attachment level (CAL), and position of gingival margin (REC) and
      radiographically for bone changes. RESULTS: Open flap debridement and GTR yielded
      statistically significant (P<0.0001) PD reduction (2.39+/- 0.92 mm and 3.44+/-
      0.78 mm), CAL gain (1.50+/- 0.99 mm and 2.89 +/- 0.90 mm), increased REC (-0.89
      +/- 0.58 mm and -0.56 +/- 0.92 mm) and bone fill (1.05+/- 0.94 mm and 2.13+/-
      1.21 mm) when 12-month data were compared to baseline. The differences between
      test and control groups were statistically significant for all parameters
      (P<0.007) except for REC (P=0.25). CONCLUSION: The use of this bioabsorbable
      membrane would seem to be effective in the treatment of intrabony defects with
      unfavorable architecture without the use of filling materials.

PMID- 16101370
TI  - Periodontitis and three health-enhancing behaviors: maintaining normal weight,
      engaging in recommended level of exercise, and consuming a high-quality diet.
AB  - BACKGROUND: Maintaining normal weight, engaging in the recommended level of
      exercise, and eating healthy food are known to improve general health. The impact
      of these behaviors on periodontal health is not well documented. This study is
      aimed at examining whether the increased number of these behaviors is associated
      with a decrease in the prevalence of periodontitis in a United States population.
      METHODS: This study utilized data on 12,110 individuals who participated in the
      third National Health and Nutrition Examination Survey. Multivariate logistic
      regression analysis was used to estimate the association between the number of
      health-enhancing behaviors and periodontitis prevalence. Health enhancing
      behaviors included maintaining normal weight (body mass index [BMI], 18.5 to 24.9
      kg/m(2)), engaging in the recommended level of exercises (>or=episodes of
      moderate or >or=episodes of vigorous-intensity physical activity per week), and
      having a high-quality diet (healthy eating index >80). RESULTS: After controlling
      for age, gender, race?ethnicity, cigarette smoking, other tobacco products,
      education, diabetes, poverty index, census region, acculturation, vitamin use,
      time since the last dental visit, dental calculus, and gingival bleeding, a 1
      unit increase in the number of the three health-enhancing behaviors was
      associated with a 16% reduction in the prevalence of periodontitis (odds ratio
      [OR]=0.84; 95% confidence interval [CI]: 0.77 to 0.93). Individuals who
      maintained normal weight, engaged in the recommended level of exercise, and had a
      high-quality diet were 40% less likely to have periodontitis compared to
      individuals who maintained none of these health-enhancing behaviors. CONCLUSION:
      An increased number of health-enhancing behaviors is associated with a lower
      periodontitis prevalence.

PMID- 16101371
TI  - Progression of experimental chronic peri-implantitis in dogs: clinical and
      radiographic evaluation.
AB  - BACKGROUND: The aim of this study was to evaluate the progression of experimental
      peri-implantitis in dogs using implants with different surface coatings. METHODS:
      Thirty-six dental implants with four different surface coatings, commercially
      pure titanium (cpTi), titanium plasma sprayed (TPS), hydroxyapatite (HA), and
      acid-etched (AE), were placed in six mongrel dogs. Five months after
      implantation, peri-implantitis was induced by cotton ligatures to facilitate
      plaque accumulation for 60 days. After 60 days, the ligatures were removed and
      supragingival plaque control was initiated for 12 months. Probing depth (PD),
      clinical attachment level (CAL), vertical bone level (VBL), horizontal bone level
      (HBL), and mobility were obtained at baseline, and 20, 40, 60 (acute phase), and
      425 days (chronic phase) after ligature removal. RESULTS: PD and CAL changed
      around all implant surfaces after ligature placement (P<0.0001). However, the
      means of PD and CAL were not statistically significant among the different
      surfaces (P>0.05). The range of CAL variation, calculated between baseline and 60
      days (acute phase) and between 60 and 425 days (chronic phase), decreased
      (P<0.05). Bone loss increased during the entire experiment (P<0.0001). The HA
      surface showed the greatest bone loss measurement (5.06+/- 0.38 mm) and the TPS
      showed the smallest bone loss (4.27+/- 0.62 mm). However, statistical
      significance was not assessed for different coatings (P>0.05). CONCLUSIONS: The
      clinical data at the initial phase showed rapid and severe peri-implant tissue
      breakdown. However, removal of ligatures did not convert the acute destructive
      peri-implant phase to a non-aggressive lesion and the progression of peri
      implantitis was observed at chronic phase. The experimental peri-implantitis in
      dogs may be a useful model to evaluate the progression of peri-implantitis.

PMID- 16101372
TI  - Oral contraceptives and periodontal diseases: rethinking the association based
      upon analysis of National Health and Nutrition Examination Survey data.
AB  - BACKGROUND: Historic evidence suggests that use of high-dose combined oral
      contraceptives (OCs) (containing >50 microg of estrogen and>or=1mg progestin)
      places women at increased risk for periodontal diseases. Since the mid-1970s, OC
      formulations have dramatically changed. This study investigated the association
      between OC use and periodontal diseases among 4,930 National Health and Nutrition
      Examination Survey (NHANES) I and 5,001 NHANES III premenopausal U.S. women, aged
      17 to 50 years, before and after the reduction of hormone levels in OCs. METHODS:
      Data for this cross-sectional study came from the first (NHANES I, 1971 to 1974)
      and third (NHANES III, 1988 to 1994) NHANES studies. RESULTS: The prevalence of
      OC use in the U.S. premenopausal female population in NHANES I was 22% and in
      NHANES III, 20%. Using multivariable logistic regression, a protective
      association between current OC use and gingivitis was suggestive but not
      significant in both NHANES I (odds ratio [OR]=0.65; 95% con- fidence interval
      [CI]: 0.42 to 1.01) and NHANES III (OR=0.80; 95% CI: 0.61 to 1.02) surveys.
      Current OC use was also associated with a decreased risk of periodontal disease
      in NHANES I (OR=0.36; 95% CI: 0.13 to 0.96) and a non-significant association in
      NHANES III (OR=0.73; 95% CI: 0.50 to 1.07). CONCLUSION: This analysis failed to
      validate the theory that earlier high- or current low-dose OC use is associated
      with increased levels of gingivitis or periodontitis and suggests an important
      reexamination of the perceived association between OC use and periodontal
      diseases.

PMID- 16101373
TI  - Effect of Er:YAG laser on diseased root surfaces: an in vivo study.
AB  - BACKGROUND: The aim of the present study was to observe in vivo the effects of
      two different power settings of an Er:YAG laser on pockets of periodontally
      involved root surfaces using a scanning electron microscope (SEM). METHODS:
      Thirty-two teeth with severe periodontal disease scheduled for extraction were
      divided into three groups: group A was irradiated with an energy of 140 mJ, 10
      Hz; group B with 160 mJ 10 Hz; group C was used as controls. Morphological
      changes on the treated root surfaces were evaluated using SEM observations to
      assess laser-induced ultrastructural changes. RESULTS: All surfaces treated in
      both groups showed a homogeneous and smooth root surface morphology. The surface
      alterations were very similar with both energy values used. CONCLUSION: Er:YAG
      laser irradiation performed with two different power settings of root surfaces in
      vivo showed at the SEM observation a complete absence of debris and smooth root
      surfaces.

PMID- 16101374
TI  - Estrogen and extracellular matrix influence human gingival fibroblast
      proliferation and protein production.
AB  - BACKGROUND: A paucity of information exists concerning how estrogen affects
      cellular function in the gingiva of women. In this study, the behavior of human
      gingival fibroblasts was examined in the presence of a potent estrogen,
      estradiol. METHODS: Quiescent, premenopausal gingival fibroblasts were incubated
      in the presence and absence of estradiol (1 nM) and/or raloxifene (100 nM). Cell
      number was determined and cell cycle analyzed using a flow cytometer. Collagen
      and non-collagen production in cell cultures grown on various extracellular
      matrices were determined using a radioactive microassay which measures
      collagenase-digestible and collagenase-resistant radiolabeled proteins. To
      ascertain if the gingiva contained specific estrogen-sensitive cell populations,
      a fluorescence-activated cell sorter was used to detect, sort, and enrich
      fibroblast populations responsive to estrogen. RESULTS: Cellular proliferation
      and the number of cells entering the S-phase of the cell cycle were significantly
      increased in mass cultures of fibroblasts stimulated by estradiol. Raloxifene did
      not antagonize the action of estradiol on cell proliferation. In regard to
      protein production, estradiol significantly reduced collagen production on
      plastic and collagen IV matrices; whereas non-collagen protein production on
      plastic and collagen I matrices was significantly reduced. Cell sorting of mass
      fibroblast populations revealed that, on average, 45% of the cells from the
      resident population selectively accumulated the estrogen probe. These sorted and
      estrogen-sensitive enriched cell populations proliferated in the presence of 1 nM
      estradiol, whereas the sorted, estrogen-deficient enriched fibroblast populations
      did not proliferate when incubated with 1 nM estradiol. CONCLUSIONS: These data
      indicate that estradiol can induce cellular proliferation while depressing
      protein production in cultures of human, premenopausal gingival fibroblasts. This
      cellular proliferation appears to be the result of a specific population of cells
      within the parent culture that responds to physiologic concentrations of
      estradiol.

PMID- 16101375
TI  - The use of surrogate variables to reflect long-term tooth survivability.
AB  - Clinical parameters used to monitor periodontal patients are usually measures of
      the disease process. They are considered surrogate variables because changes in
      their status are interpreted to have an impact on the ultimate goal of
      periodontal therapy, which is tooth retention. However, their ability to reflect
      tooth survivability has been questioned because there is a lack of long-term data
      to validate that stable or improved surrogates result in reduced tooth loss.
      Therefore, to clarify the utility of employing surrogates to reflect long-term
      tooth retention, a number of issues related to their use are discussed in this
      commentary: phraseology, benefits and shortcomings, biologic credibility, and
      their previous successful utilization in monitoring the effects of therapy. This
      commentary supports the reasonableness of using surrogates to monitor periodontal
      status and suggests that a combination of surrogates that represent "periodontal
      clinical health" should be considered a true endpoint of periodontal therapy,
      since this outcome provides a condition conducive to tooth retention.

PMID- 16101376
TI  - Re: Relative connective tissue graft size affects root coverage treatment outcome
      in the envelope procedure.

PMID- 16101377
TI  - Position paper: epidemiology of periodontal diseases.

PMID- 16101380
TI  - Antiproliferative efficacy of angiotensin II receptor blockers in prostate
      cancer.
AB  - An apparent low prevalence of cancer in hypertensive patients receiving
      angiotensin converting enzyme inhibitors is reported; however, the molecular
      mechanisms have not been elucidated. Angiotensin-II (Ang-II) is well known to be
      associated with hypertension, as a main peptide of the renin-angiotensin system,
      and its detailed molecular mechanisms have recently been elucidated. For
      instance, Ang-II directly activates the mitogenic signal transduction pathway
      through the angiotensin-II type-1 (AT1) receptor in smooth muscle cells and
      cardiac myocytes. Ang-II receptor blockers (ARBs), a class of antihypertensive
      agent, suppress signal transduction pathways mediated by growth factors such as
      epidermal growth factor (EGF), through the AT1 receptor. Our studies demonstrated
      that an ARB had the potential for antiproliferative effects and inhibition of
      angiogenesis in prostate cancer cells. The AT1 receptor is categorized in the
      guanosine phosphate binding protein-coupled receptors (GPCRs), which are viewed
      as critical regulators of the interactions between epithelial and stromal cells.
      Hence, we consider that in overcoming prostate cancer, it is very important to
      inhibit GPCR signaling in cancer cells by ARBs. It is unclear how prostate cancer
      growth changes from being hormone dependent to independent, and no effective
      therapy has therefore been developed. Our clinical data revealed that ARB
      administration decreased prostate specific antigen (PSA) and improved performance
      status in patients with hormone-refractory prostate cancer. This review provides
      an insight into the key role of Ang-II and the possibility of ARBs for molecular
      targeting of mitogenesis and angiogenesis in prostate cancer.

PMID- 16101381
TI  - Inflammation and cancer: when NF-kappaB amalgamates the perilous partnership.
AB  - Chronic inflammation has long been suggested to constitute a risk factor for a
      variety of epithelial cancers such as malignancies of prostate, cervix,
      esophagus, stomach, liver, colon, pancreas, and bladder. An inflammatory response
      is typically accompanied by generation of free radicals, stimulation of
      cytokines, chemokines, growth and angiogenic factors. Free radicals, capable of
      both directly damaging DNA and affecting the DNA repair machinery, enhance
      genetic instability of affected cells, thus contributing to the first stage of
      neoplastic transformation also known as "initiation". Cytokines and growth
      factors can further promote tumor growth by stimulating cell proliferation,
      adhesion, vascularization, and metastatic potential of later stage tumors.
      Nuclear factor kappa B (NF-kappaB) is a family of ubiquitously expressed
      transcription factors that are widely believed to trigger both the onset and the
      resolution of inflammation. NF-kappaB also governs the expression of genes
      encoding proteins essential in control of stress response, maintenance of
      intercellular communications, and regulation of cellular proliferation and
      apoptosis. Recent data have expanded the concept of inflammation as a critical
      component in carcinogenesis suggesting new anti-inflammatory therapies for a
      complementary approach in treating a variety of tumor types. These observations
      highlighted the NF-kappaB pathway as an attractive avenue for drug discovery and
      development. The present review will outline recent advances in our understanding
      of NF-kappaB function in the inflammatory processes and its input in tumor
      initiation/promotion, as well as summarize the development of animal and cell
      culture models for validating drug candidates with NF-kappaB-modulating
      activities, and applications of the latter in cancer therapy.

PMID- 16101382
TI  - Molecular targets from VHL studies into the oxygen-sensing pathway.
AB  - Inheritance of a faulty von Hippel-Lindau (VHL) tumor suppressor gene is the
      cause of VHL disease, a rare multisystemic autosomal dominant disorder
      characterized by the development of hypervascular tumors in a number of organs,
      including the retina, brain, spine, pancreas, adrenal gland, and the kidney.
      Recent discoveries have demonstrated that the VHL gene product pVHL serves as a
      substrate-recognition component of an E3 ubiquitin ligase complex that targets
      hypoxia-inducible factor (HIF) transcription factor for polyubiquitination and
      subsequent degradation. Accordingly, tumor cells devoid of functional pVHL show
      an inappropriate accumulation of HIF, as well as downstream HIF-target genes,
      such as vascular endothelial growth factor (VEGF), a potent angiogenic factor.
      Furthermore, HIF has been found to be elevated in many human cancers further
      underscoring its common significance in oncogenesis. These and other related
      recent findings have shed significant insight into the mechanisms governing
      mammalian cellular oxygen homeostasis and how disruptions in this oxygen-sensing
      pathway can lead to tumorigenesis. Next generation anti-cancer drugs will
      undoubtedly emerge from our understanding of the molecular pathways governing
      normal cellular metabolism, growth and differentiation that have gone awry during
      neoplastic transformation, and studies in VHL disease will serve as one of the
      proving grounds for the efficacy of 'designer' anti-cancer drugs tailored against
      the VHL-HIF pathway.

PMID- 16101383
TI  - The therapeutic potential of 4-1BB (CD137) in cancer.
AB  - Techniques for modulating immune cells for cancer therapy have been widely
      studied. One key approach that is being clinically tested is developing tumor
      destructive cell-mediated immune responses by regulating co-stimulatory
      molecules. 4-1BB (CD137), a member of the TNF receptor family, is expressed
      following activation of T and NK cells. Recently, it has been reported that DCs
      also express 4-1BB. Cross-linking of 4-1BB provides a potent co-stimulatory
      signal for lymphocytes via signal transduction pathways that modulate a number of
      cellular responses. One remarkable response is stimulation of anti-tumor activity
      in vivo and in vitro. We here review the potential role of 4-1BB in cancer
      immunotherapy focusing on the cellular and molecular mechanisms involved.

PMID- 16101384
TI  - The MCM complex: its role in DNA replication and implications for cancer therapy.
AB  - The MCM complex controls the once per cell cycle DNA replication in eukaryotic
      cells. In a process known as DNA replication licensing, it primes chromatin for
      DNA replication by binding origins of DNA replication during the late M to early
      G1 phase of the cell cycle. Activated by S phase promoting protein kinases, the
      origin-bound MCM complexes unwind the double stranded DNA at the origins, recruit
      DNA polymerases and initiate DNA synthesis. Coupled with the initiation of DNA
      replication in the S phase, the MCM complexes move away from replication origins
      as a component of the DNA replication fork, likely serving as DNA helicases.
      Their departure deprives replication origins the ability to re-initiate DNA
      replication for the reminder of the cell cycle. Because of its vital role in
      genome duplication in proliferating cells, deregulation of the MCM function
      results in chromosomal defects that may contribute to tumorigenesis. The MCM
      proteins are highly expressed in malignant human cancers cells and pre-cancerous
      cells undergoing malignant transformation. They are not expressed in
      differentiated somatic cells that have been withdrawn from the cell cycle.
      Therefore, these proteins are ideal diagnostic markers for cancer and promising
      targets for anti-cancer drug development. In this article, I will overview the
      structures and functions of the MCM complex with an effort to integrate insights
      from recent biochemical and structural studies. Discussions will also cover
      activities and structures of the complex that may be useful for the development
      of drug screens.

PMID- 16101385
TI  - Protein misfolding and misprocessing in complex disease.
AB  - Scientists from over 20 major research centers recently convened to discuss
      advances and new discoveries in "Protein MisFolding and MisProcessing in
      Disease." Understanding protein mechanisms the underlying etiology of complex
      diseases lies in analyzing the associated biochemical mechanisms, which include
      folding patterns, processing patterns, chaperone regulators, stress pathways, and
      signal transduction.

PMID- 16101386
TI  - Pharmacological characterisation of spider antimicrobial peptides.
AB  - Most spider antimicrobial peptides share a common mechanism of membrane
      permeabilisation and the innate immune systems of the pathogen. In this review,
      we present recent accounts of the application at the preclinical level that
      should be tried and the range of bioactivities and their particular structure can
      be harnessed for molecular engineering applications and in drug design.
      Structural analyses such as amino acid sequence and circular dichroism are
      described. Conductance measurements and pharmacological studies of the action on
      the inner or outer membranes of anti-microbe will reveal more about the mode of
      action of the antimicrobial peptides of spider.

PMID- 16101387
TI  - The role of Abeta peptides in Alzheimer's disease.
AB  - The Abeta peptide has been identified as central to the onset and development of
      Alzheimer's disease (AD) and several hypotheses about toxicity involving Abeta
      peptides have been proposed including mechanisms of oxidative stress and
      disruption of calcium homeostasis. The biology, structure and physical properties
      of Abeta peptides are discussed, as well as existing therapeutics and future
      strategies for the treatment of AD.

PMID- 16101388
TI  - Preliminary structural studies of the hydrophobic ribosomal P0 protein from
      Trypanosoma cruzi, a part of the P0/P1/P2 complex.
AB  - The Trypanosoma cruzi ribosomal P0 protein (TcP0) is part of the ribosomal stalk,
      which is an elongated lateral protuberance of the large ribosomal subunit
      involved in the translocation step of protein synthesis. The TcP0 C-terminal
      peptide is highly antigenic and a major target of the antibody response in
      patients with systemic lupus erythematosus and patients suffering chronic heart
      disease produced by Trypanosoma cruzi infection. The structural properties of
      TcP0 have been explored by circular dichroism, tryptophan fluorescence and
      limited proteolysis experiments. These studies were complemented by secondary
      structure consensus prediction analysis. The results suggest that the tertiary
      structure of TcP0 could be described as a compact, stable, trypsin-resistant, 200
      residues long N-terminal domain belonging to the alpha/beta class and a more
      flexible, degradable, helical, 123 residues long C-terminal domain which could be
      involved in the formation of an unusual hydrophobic zipper with the ribosomal
      P1/P2 proteins to form the P0/P1/P2 complex.

PMID- 16101389
TI  - Expression, purification and partial characterization of the Kruppel-associated
      box (KRAB) from the human ZNF2 protein.
AB  - The Kruppel-associated box (KRAB) domain is a potent transcription repression
      bipartite domain, shared by over 400 zinc finger proteins in humans, involved in
      the regulation of many functions. KRAB domains are both physically and
      functionally bipartite (A and B modules). The lone KRAB-A and composite KRAB-AB
      domains from the human ZNF2 protein were over-expressed as recombinant proteins
      in E. coli, isolated and purified to homogeneity to investigate their structure
      to function relationship.

PMID- 16101390
TI  - Influence of disulfide bonds on the conformational changes and activities of
      refolded phytase.
AB  - Aspergillus sp. phytase contains five disulfide bonds. In order to elucidate
      their role, the reactivation and refolding of phytase in the absence and presence
      of dithiothreitol (DTT) was investigated. The results indicated that the
      disulfide bonds play an important role in the catalytic activity and
      conformational stability of the enzyme.

PMID- 16101391
TI  - NMR assignment and secondary structure of the Coxsackievirus and Adenovirus
      receptor domain 2.
AB  - The Coxsackievirus and Adenovirus receptor (CAR) mediates entry of coxsackievirus
      and adenovirus. CAR possesses an extracellular region that is comprised of 2 Ig
      domains termed CAR-D1 and CAR-D2. The 1H, 13C and 15N resonances of CAR-D2 have
      been assigned and the secondary structure has been deduced.

PMID- 16101392
TI  - Energy barrier for protein adhesion and crystal nucleation on flat alien
      substrates.
AB  - From the experimentally defined rate of heterogeneous formation of protein
      crystals and number of collisions between protein molecules with substrate, the
      energy barrier for adhesion of protein molecule to alien materials is estimated.
      According to the Boltzmann equation for energy distribution this barrier is of
      the order of 10(-12) erg per molecule.

PMID- 16101393
TI  - Direct comparison of the crystal and solution structure of glucose/xylose
      isomerase from Streptomyces rubiginosus.
AB  - Glucose isomerase (D-xylose ketol-isomerase, EC 5.3.1.5.) catalyses the
      isomerization reaction of glucose and xylose. The small angle X-ray scattering
      (SAXS) data of glucose/xylose isomerase from Streptomyces rubiginosus were
      recorded for protein solution using synchrotron radiation. The experimental data
      were compared with theoretical scattering calculated on the basis of the known
      crystal structure (PDB code: 1OAD). The radius of gyration measured by SAXS
      (R(G)=3.30 nm) was almost identical and the maximum dimension in the distance
      distribution function was by about 2.5 % lower than the corresponding values
      calculated on the basis of the crystal structure.

PMID- 16101394
TI  - Production of the human-beta-defensin using Saccharomyces cerevisiae as a host.
AB  - Studies of the human defensins have been hampered by the lack of a simple
      expression system allowing for rapid production of functional peptide forms.
      Here, we describe a Saccharomyces cerevisiae AH22 expression system that meets
      that condition. The 42 amino acid form of human beta-defensin-1 was expressed
      under the control of the ADH1 promoter. The optimum conditions for expression
      were determined and the stable maintenance of the pVT103L-hBD-1 chimeric vector
      in the yeast population was confirmed. Expressed hBD-1 was secreted into the
      medium (approximately 55 microg l(-1)) and purified using cation-exchange
      chromatography. Isolated defensin exhibited strong bactericidal effect on
      Escherichia coli ML-35p. We conclude that the expression system described here
      will be a useful tool where readily prepared and active forms of the human
      defensins are needed.

PMID- 16101395
TI  - A general procedure for the production of antibody reagents against eukaryotic
      ribosomal proteins.
AB  - Despite recent progress in the structural and functional analysis of bacterial
      and archaeal ribosomes, the structure and biogenesis of eukaryotic ribosomes
      still awaits a detailed characterization. Ribosomal protein-specific antibodies
      would be valuable tools for such studies, but their production is commonly
      hindered by the poor expression and solubility of eukaryotic ribosomal proteins
      in E. coli. We report here an improved general procedure for the over-production
      of recombinant eukaryotic ribosomal proteins and for the generation of the
      corresponding polyclonal antibodies. The specificity and sensitivity of detection
      of the antibodies produced by this procedure are documented.

PMID- 16101396
TI  - Screening and purification of a novel trypsin inhibitor from Prosopis juliflora
      seeds with activity toward pest digestive enzymes.
AB  - Several pests are capable of decreasing crop production causing severe economical
      and social losses. Aiming to find novel molecules that could impede the digestion
      process of different pests, a screening of alpha-amylase and trypsin-like
      proteinase inhibitors was carried out in Prosopis juliflora, showing the presence
      of both in dry seeds. Furthermore, a novel trypsin inhibitor, with molecular mass
      of 13,292 Da, was purified showing remarkable in vitro activity against T.
      castaneum and C. maculatus.

PMID- 16101397
TI  - Characterization of expression and stability of recombinant cystein-rich protein
      human MT1A from yeast.
AB  - Metallothionein (MT) is the protein that has been shown to bind heavy metals,
      scavenge free radicals, protect DNA from radiation damage, and alleviate disease
      symptoms. However, only very limited success has been achieved in expression and
      production of active recombinant metallothionein. In this study, human
      metallothionein 1A (hMT1A) was transformed into yeast Pichia pastoris for
      expression with secretion of the protein into the medium. The expression system
      was optimized to obtain the targeted protein in active form at 335 mg per litre
      culture. hMT1A showed the character of extreme instability in the experiment.
      High concentration, aeration and heavy metal ions are the main factors affecting
      hMT1A stability.

PMID- 16101398
TI  - Global changes of chlorophyll excitonic interactions in photosystem II during
      thermal denaturation.
AB  - Photosystem II (PSII) is a multisubunit chlorophyll-binding enzyme that absorbs
      light to catalyze water oxidation and plastoquinone reduction. Chlorophyll
      excitonic interaction changes in PSII were studied by absorption and circular
      dichroism spectra from 25 degrees C to 80 degrees C, and protein subunit
      denaturation was monitored by differential scanning calorimetry. A four-stage
      process of chlorophyll excitonic interaction change was observed being correlated
      with the denaturation of protein subunits.

PMID- 16101399
TI  - Further studies on the side reactions associated with use of N(pi)
      benzyloxymethylhistidine.
AB  - The use of N(alpha)-tert.-butyloxycarbonyl-N(pi)-benzyloxymethylhistidine [Boc
      His(Bom)] in peptide synthesis results in a serious level of side products
      arising from the generation of formaldehyde during the HF cleavage reaction. In
      particular, when treating a His(Bom)-containing peptide having Cys at the N
      terminus by HF, this leads to almost complete conversion of the Cys-peptide to
      thiazolidyl (Thz)-peptide unless precautions are taken. Also, the reaction of
      formaldehyde with the N-terminal Trp and the N-methylanthranyl (Nma) group was
      found to produce tetrahydro-beta-carboline and dihydroquinazolin derivatives,
      respectively, upon isolation from HF mixtures. The addition of cysteine as a
      scavenger in HF proved to be effective for suppressing modification arising from
      the generation of formaldehyde.

PMID- 16101400
TI  - Purification of a 6.5 kDa protease inhibitor from Amazon Inga umbratica seeds
      effective against serine proteases of the boll weevil Anthonomus grandis.
AB  - A 6.5 kDa serine protease inhibitor was purified by anion-exchange chromatography
      from the crude extract of the Inga umbratica seeds, containing inhibitor isoforms
      ranging from 6.3 to 6.7 kDa and protease inhibitors of approximately 19 kDa. The
      purified protein was characterized as a potent inhibitor against trypsin and
      chymotrypsin and it was named I. umbratica trypsin and chymotrypsin inhibitor
      (IUTCI). MALDI-TOF spectra of the IUTCI, in the presence of DTT, showed six
      disulfide bonds content, suggesting that this inhibitor belongs to Bowman-Birk
      family. The circular dichroism spectroscopy indicates that IUTCI is predominantly
      formed by unordered and beta-sheet secondary structure. It was also
      characterized, by fluorescence spectroscopy, as a stable protein at range of pH
      from 5.0 to 7.0. Moreover, this inhibitor at concentration of 75 microM presented
      a remarkable inhibitory activity (60%) against digestive serine proteases from
      boll weevil Anthonomus grandis, an important economical cotton pest.

PMID- 16101401
TI  - Two novel lectins from Parkia biglandulosa and Parkia roxburghii: isolation,
      physicochemical characterization, mitogenicity and anti-proliferative activity.
AB  - Two mannose/glucose specific seed lectins were isolated from Parkia biglandulosa
      and Parkia roxburghii and were characterized w.r.t various physicochemical
      properties. Unlike other Parkia lectins a comparison of native and subunit
      molecular mass showed that both Parkia lectins were heterotetramers. Parkia
      biglandulosa lectin was found to be T-cell mitogen as revealed by IL-2 bioassay.
      These lectins showed anti-proliferative effect on two murine macrophage cancer
      cell lines i.e. P 388DI (50%) and J774 (70%). In addition Parkia roxburghii also
      inhibited proliferation of HB98 (65.47%), a B-cell hybridoma cell line.

PMID- 16101402
TI  - Effects of trehalose on pressure-induced inactivation of yeast alcohol
      dehydrogenase.
AB  - Isozymes of yeast alcohol dehydrogenase are slowly denatured at moderate
      hydrostatic pressures (<3 kbar). The time courses for inactivation are biphasic
      and both phases of both isozymes are protected by trehalose. ADH-I is slightly
      more barostable than ADH-II which is opposite to their thermostabilities.
      Trehalose at 1M extends their half-lives about 6-fold at 2 kbar, pH 7.5 and 25
      degrees C. In contrast, 1M sucrose provides only 4.4-fold protection under
      identical conditions, a finding consistent with the superior protein
      stabilization of trehalose to other denaturants.

PMID- 16101403
TI  - Innovative, multifunctional sequential oligopeptide carriers Soc(n)-I and SOC(n)
      II: functions-technology-perspectives.
AB  - An innovative type of multifunctional helicoid artificial carriers, formed by the
      repetitive Lys-Aib-Gly (SOC(n)-I) or by the Aib-Lys-Aib-Gly (SOC(n)-II), with
      structural rigidity and regularity were successfully applied in our laboratory
      for anchoring antigenic/immunogenic peptides. The carriers, designed to display a
      predetermined 3D structure, adopt the 3(10) helical conformation, while the
      attached peptides preserve their original "active" conformation. The constructed
      conjugates were used as substrates in solid phase immunoassays, as well as for
      generating potent and specific immune responses.

PMID- 16101404
TI  - Preliminary x-ray crystallographic analysis of centrin from ciliate Euplotes
      octocarinatus.
AB  - Centrins are four-EF-hand Ca(2+)-binding proteins, which belong to the CaM super
      family. The centrin from ciliate Euplotes Octocarinatus has been expressed in
      Escherichia coli, purified and crystallized using the hanging-drop method. Rod
      like crystals were grown and diffracted to 2.0 angstroms. The crystals belong to
      space group P2(1)2(1)2(1) and the unit-cell parameters are a=34.442 angstroms,
      b=48.954 angstroms, c=72.583 angstroms.

PMID- 16101406
TI  - Non-steroidal progesterone receptor specific ligands.
AB  - The nuclear receptor for progesterone is a target for contraception and for
      several therapeutic indications. Progestin agonists and antagonists in clinical
      use mimic the steroidal backbone of the cognate ligand, progesterone. Thus, they
      have significant cross-reactivity with other steroid receptors. Recently, non
      steroidal progesterone receptor ligands have begun to appear in the literature.
      This review will describe the current status of research into these promising new
      chemical entities.

PMID- 16101407
TI  - Molecular mechanisms of mineralocorticoid receptor antagonism by eplerenone.
AB  - Mineralocorticoid receptor (MR) antagonism has proven to effectively attenuate
      the pathophysiological effects of aldosterone in clinical and experimental
      settings of hypertension and heart failure. MR activates transcription of target
      genes upon aldosterone binding, and eplerenone selectively binds to MR and blocks
      aldosterone- mediated activation. In this review, we summarize the preclinical
      and clinical evidence supporting the beneficial effects of eplerenone (INSPRA), a
      selective aldosterone blocker, in the treatment of hypertension and heart
      failure. We also review the current status in understanding the molecular
      mechanisms of action of the MR and its ligand. In addition, we compare the
      effects of eplerenone and spironolactone, a nonselective aldosterone blocker, on
      the transcriptional activity of MR and provide a molecular explanation for the
      improved side-effect profile of eplerenone compared with spironolactone.

PMID- 16101408
TI  - FXR, a therapeutic target for bile acid and lipid disorders.
AB  - The farnesoid X receptor (FXR) is a nuclear receptor expressed in tissues exposed
      to high concentrations of bile acids such as the liver, kidney and intestine and
      functions as a bile acid sensor. FXR regulates the expression of various
      transport proteins and biosynthetic enzymes crucial to the physiological
      maintenance of lipids, cholesterol and bile acid homeostasis. The concept of
      reverse endocrinology, whereby the receptor is identified first, followed by the
      identification of ligands and the sequential elucidation of the physiological
      role of the receptor has been widely used for a number of orphan nuclear
      receptors. The design of synthetic high affinity ligands acting via these
      receptors not only helps to decipher the function of the receptor, but also
      should lead to the development of novel and highly specific drugs. The bile acid
      receptor FXR is a perfect example where this strategy helped with understanding
      the role of this receptor in cholesterol and bile acid homeostasis. Regulation of
      FXR through small-molecule drugs represents a promising therapy for diseases
      resulting from lipid, cholesterol and bile acid abnormalities.

PMID- 16101409
TI  - The pharmacology of LXR.
AB  - Liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily
      of ligand-activated transcription factors. Two LXRs (LXRalpha and LXRbeta) were
      initially characterized as orphan members of this superfamily with disparate
      patterns of tissue expression. These two receptors later were recognized as
      sterol-responsive with the ability to directly bind several oxysterol
      metabolites. Many LXR target genes have been identified that implicate these
      receptors in a variety of physiological processes including cholesterol transport
      and metabolism, glucose metabolism, and inflammation. Synthetic LXR ligands have
      been designed with the potential to treat disorders such as atherosclerosis and
      diabetes. In this review, we describe the potential utility of LXR ligands in the
      treatment of disease.

PMID- 16101410
TI  - PPARs as targets for metabolic and cardiovascular diseases.
AB  - Peroxisome proliferator-activated receptors (PPARs) alpha, gamma and delta (beta)
      are ligand-activated transcription factors of the nuclear hormone receptor
      superfamily which have been shown to play key roles in maintaining glucose and
      lipid homeostasis. The physiological effects of several marketed drugs for the
      treatment of dyslipidemia (fenofibrate and gemfibrozil) and diabetes
      (rosiglitazone and pioglitazone) have now been shown to be mediated through
      PPARalpha and PPARgamma respectively. Over the past few years our understanding
      of how PPAR ligands and receptors modulate gene expression has greatly increased;
      this knowledge is being used to design even more potent and efficacious PPAR
      ligands for the treatment of diabetes, dyslipidemia, atherosclerosis and obesity.
      This review is a brief survey of the PPAR field which highlights recent progress,
      with an emphasis on new ligands with novel PPAR profiles, particularly compounds
      which are co-agonists of PPAalpha, gamma and beta (delta).

PMID- 16101411
TI  - Retinoids as therapeutic agents: today and tomorrow.
AB  - Retinoids have shown beneficial therapeutic effects in pre-clinical and animal
      models for multiple pathologic indications, however severe adverse effects,
      restricting dosage and efficacy of oral formulations limit their use in patients.
      The focus of this review includes the actual medicinal use of retinoids and
      chemical efforts to generate highly selective and less toxic synthetic retinoids.

PMID- 16101412
TI  - Vitamin D receptor modulators for inflammation and cancer.
AB  - 1alpha, 25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active form of
      vitamin D, is an important hormone that is critically required for the
      maintenance of mineral homeostasis and structural integrity of bones. 1,25
      (OH)2D3 accomplishes this by facilitating calcium absorption from the gut and by
      a direct action on osteoblasts, the bone forming cells. Apart form its classical
      actions on the gut and bone, 1,25-(OH)2D3 and its synthetic analogs also possess
      potent anti-proliferative, differentiative and immunomodulatory activities. 1,25
      (OH)2D3 exerts these effects through vitamin D receptor (VDR), a ligand-dependent
      transcription factor that belongs to the superfamily of steroid/thyroid
      hormone/retinoid nuclear receptors. The presence of VDR in various tissues other
      than gut and bone, along with their ability to exert differentiation, growth
      inhibitory and anti-inflammatory action, has set the stage for therapeutic
      exploitation of VDR ligands for the treatment of various inflammatory indications
      and cancer. However, the use of VDR ligands in clinic is limited by their major
      dose-related side effect, namely hypercalcemia/hypercalciuria. Efforts are being
      undertaken to develop vitamin D receptor modulators (VDRMs) that are tissue
      selective and/or gene-selective in their action and these ligands may exhibit
      increased therapeutic indices. This review explores the recent advances in VDR
      biology, non-secosteroidal VDR ligands and the current and potential clinical
      applications of VDR ligands in inflammation and cancer.

PMID- 16101414
TI  - Hierarchical docking of databases of multiple ligand conformations.
AB  - Ligand flexibility is an important problem in molecular docking and virtual
      screening. To address this challenge, we investigate a hierarchical pre
      organization of multiple conformations of small molecules. Such organization of
      pre-calculated conformations removes the exploration of ligand conformational
      space from the docking calculation and allows for concise representation of what
      can be thousands of conformations. The hierarchy also recognizes and prunes
      incompatible conformations early in the calculation, eliminating redundant
      calculations of fit. We investigate the method by docking the MDL Drug Data
      Report (MDDR), an annotated database of 100,000 molecules, into apo and holo
      forms of seven unrelated targets. This annotated database allows us to track the
      ranking of tens to hundreds of annotated ligands in each of the docking systems.
      The binding sites and database are prepared in an automated fashion in an attempt
      to remove some human bias from the calculations. Many thousands of explicit and
      implicit ligand conformations may be docked in calculations not much longer than
      required for single conformer docking. As long as internal energies are not
      considered, recombination with the hierarchy is additive as the number of degrees
      of freedom is increased. Molecules with even millions of conformations can be
      docked in a few minutes on a single desktop computer.

PMID- 16101415
TI  - Library design for fragment based screening.
AB  - According to Hann's model of molecular complexity an increased probability of
      detection binding to a target protein can be expected when small, low complex
      molecular fragments are screened with high sensitivity instead of full-sized
      ligands with lower sensitivity. Analysis of the HTS summary data of Novartis and
      comparison with NMR screening results obtained on generic fragment libraries
      indicate this expectation to be true with hitrates of 0.001% - 0.151% observed in
      the identification of ligands with an IC(50) threshold in the micromolar range in
      an HTS setup and hitrates above or equal to 3% observed in NMR screening of
      fragments with an affinity threshold in the millimolar range. It is however
      necessary to keep in mind that the sets of target studied were not identical for
      both method and the experience in NMR screening is too limited for a final
      conclusion. The term hitrate as used here reflects only the success rate in the
      observation of ligand binding event. It must not be confused with the overall
      success rate of fragment and high throughput screening in the lead finding
      process, which can be entirely different, since the steps required to follow-up a
      ligand binding event to a lead are different for both methods. A survey of
      fragment-based lead discovery case studies given in the literature shows that in
      approximately half of the cases the initial hit fragment was discovered by
      screening a generic library, whereas in the other cases some knowledge about an
      initial ligands or the protein binding site has been used, whereas systematic
      virtual screening of fragment databases has been only rarely reported. As
      comparatively high hitrates were obtained, further consideration to optimize the
      generic fragment screening library were directed to the chemical tractability of
      the fragment. As several functional groups preferred by chemists for modification
      and linking of the fragments are also preferentially involved in interactions
      between the fragments and the target protein, a set of screening fragments was
      derived from chemical building blocks by masking its linker group by a chemical
      transformation which can be later on used in the chemical follow-up of the
      fragment hit. For example primary amines can be masked as acetamides. If the
      screening fragment is active the related building block can then be used for
      synthesis of a follow-up library.

PMID- 16101416
TI  - Chemical and biological profiling of an annotated compound library directed to
      the nuclear receptor family.
AB  - Nuclear receptors form a family of ligand-activated transcription factors that
      regulate a wide variety of biological processes and are thus generally considered
      relevant targets in drug discovery. We have constructed an annotated compound
      library directed to nuclear receptors (NRacl) as a means for integrating the
      chemical and biological data being generated within this family. Special care has
      been put in the appropriate storage of annotations by using hierarchical
      classification schemes for both molecules and nuclear receptors, which takes the
      ability to extract knowledge from annotated compound libraries to another level.
      Analysis of NRacl has ultimately led to the identification of scaffolds with
      highly promiscuous nuclear receptor profiles and to the classification of nuclear
      receptor groups with similar scaffold promiscuity patterns. This information can
      be exploited in the design of probing libraries for deorphanization activities as
      well as for devising screening batteries to address selectivity issues.

PMID- 16101417
TI  - Web enabling technology for the design, enumeration, optimization and tracking of
      compound libraries.
AB  - Motivated by the need to augment Merck's in-house small molecule collection, web
      based tools for designing, enumerating, optimizing and tracking compound
      libraries have been developed. The path leading to the current version of this
      Virtual Library Tool Kit (VLTK) is discussed in context of the (then) available
      commercial offerings and the constraints and requirements imposed by the end
      users. Though the effort was initiated to simplify the tasks of designing novel,
      drug-like and diverse compound libraries containing between 2K-10K unique
      entities, it has also evolved into a powerful tool for outsourcing syntheses as
      well as lead identification and optimization. The web tool includes components
      that select reagents, analyze synthons, identify backup reagents, enumerate
      libraries, calculate properties, optimize libraries and finally track the
      synthesized compounds through biological assays. In addition to accommodating
      project specific designs and virtual 3D library scanning, the application
      includes tools for parallel synthesis, laboratory automation and compound
      registration.

PMID- 16101418
TI  - Information extraction in the life sciences: perspectives for medicinal
      chemistry, pharmacology and toxicology.
AB  - Information extraction approaches have been successfully applied to mine the
      scientific literature in biology and medicine. So far, the main focus of research
      and development in this domain was on the recognition and extraction of gene and
      protein names in the context of molecular biology and genome research and on
      disease names and other medical terms in the context of clinical research.
      Similar to biology and medical sciences, medicinal chemistry, pharmacology and
      toxicology are descriptive sciences. However, information extraction approaches
      in these disciplines encounter a number of problems that are specific to the fact
      that these scientific areas are essentially centred at chemical compounds and
      their structures. In this review, we will give a short overview on general
      information extraction strategies in the life sciences and we will introduce new
      approaches to apply information extraction to the domain of pharmacology,
      medicinal chemistry and toxicology. Finally, we will emphasize on how information
      extraction approaches will support public and commercial research in medicinal
      chemistry, pharmacology and toxicology by linking information on chemical
      structures to biological information.

PMID- 16101419
TI  - Potency-scaled partitioning in descriptor spaces with increasing dimensionality.
AB  - Partitioning algorithms are described that operate in chemical reference spaces
      formed by combinations of binary-transformed molecular descriptors and aim at the
      identification of potent hits in ligand-based virtual screening. One of these
      approaches depends on mapping of consensus positions of compound activity sets in
      descriptor spaces followed by step-wise extension of the dimensionality of these
      spaces and re-mapping of activity-dependent consensus positions. Dimension
      extension is carried out to increase the discriminatory power of descriptor
      combinations and distinguish database compounds from potential hits. This method
      was originally named Dynamic Mapping of Consensus positions (DMC) and
      subsequently extended in order to take different potency levels of known active
      molecules into account and increase the probability of recognizing potent
      database hits. The extension was accomplished by adding potency scaling to DMC
      calculations, and the resulting approach was termed POT-DMC. Results of
      comparisons of DMC and POT-DMC calculations on different classes of active
      compounds with substantially varying potency levels support the validity of the
      POT-DMC approach.

PMID- 16101420
TI  - Progress in the development of selective inhibitors of aurora kinases.
AB  - Errors in the mitotic process are thought to be one of the principal sources of
      the genetic instability that hallmarks cancer. Unsurprisingly, many of the
      proteins that regulate mitosis are aberrantly expressed in tumour cells when
      compared to their normal counterparts. These may represent a good source of
      targets for the development of novel anti-cancer agents. The Aurora kinases
      represent one such family of mitotic regulators. In recent years there has been
      intense interest in both understanding the role of the Aurora kinases in cell
      cycle regulation and also in developing small molecule inhibitors as potential
      novel anti-cancer drugs. With several companies now starting to take Aurora
      kinase inhibitors into clinical development, the time is right to review the
      medicinal chemistry contribution to developing the field, in particular to review
      the increasingly broad range of small molecule inhibitors with activity against
      this kinase family.

PMID- 16101421
TI  - Nitric oxide.

PMID- 16101422
TI  - An introduction to NO-related therapeutic agents.
AB  - Investigational NO-related therapeutic agents span the range from prodrugs that
      elevate NO levels, to scavengers of NO, and inhibitors of endogenous NO
      synthesis. Related agents that influence nitrogen oxides, in addition to NO
      itself, are also to be considered. Organic nitrates have been used for over 130
      years in cardiovascular therapy and hybrid nitrates continue to lead the way in
      clinical development for an increasing range of disease states. Selectivity for
      inhibition of NO synthase (NOS) isoforms is a continuing goal. Conversely, N
      hydroxyarginine derivatives are substrates for NOS and represent a new NO donor
      class. Diazeniumdiolate (NONOate) NO donors have been essential for understanding
      of NO biology and are being developed as NO donor and HNO donor prodrugs
      including as photolabile sources. N-Hydroxyurea has been used as a cancer drug
      for decades and is approved for sickle cell disease treatment, but also provides
      a lead compound for design of NO and HNO donors. Nitroaliphatics and
      nitrosoaliphatics also represent chemical classes that include NO donors and
      exhibit biological activity that mimics that of NO. Nitroprusside has been in use
      since the 1920's and metal ion complexes continue to be explored, including as
      caged NO donors. Clear and exciting opportunities exist for new therapies based
      upon NO-related drugs. Despite the extensive clinical use of NO donor drugs and
      the role of NOS activation in the action of several prescription medications,
      challenges remain to the development of new NO-related therapeutics, but these
      are surmountable and are outweighed by the opportunities.

PMID- 16101423
TI  - Selective neuronal nitric oxide synthase inhibitors.
AB  - This review includes the non-patent literature up to October 2004 that deals with
      selective neuronal nitric oxide synthase inhibitors (highest potency is for the
      neuronal isozyme). Some non-selective inhibitors or selective inducible nitric
      oxide synthase inhibitors are mentioned if they are related to compounds that are
      discussed; structures of these compounds generally are not given. In vitro
      inhibition constants are given either as IC(50) values or as K(i)values. An
      IC(50) value, the inhibitor concentration that produces 50% inhibition in the
      presence of a constant concentration of substrate, is obtained by extrapolation
      of several rate data points to 50% inhibition. K(i) values are derived from
      several types of plots that relate the concentration of inhibitor with enzyme
      velocity in the presence of a variety of substrate concentrations [1]. The K(i)
      value can be estimated from the IC(50) value [2]. Although the two inhibition
      constants are related, they are not the same; generally, the reported K(i) values
      tend to be lower than the IC(50) values. If specifics are desired about how the
      data were collected, then the reader will have to look in the literature cited.
      No attempt was made to be exhaustive in citing all references related to specific
      inhibitors; rather, examples of literature references are given for each
      inhibitor described.

PMID- 16101424
TI  - Nitric oxide (NO)- and nitroxyl (HNO)-generating diazeniumdiolates (NONOates):
      emerging commercial opportunities.
AB  - Diazeniumdiolate ions are convenient and, for a variety of applications, uniquely
      advantageous nitric oxide (NO) dosage forms. Ionic diazeniumdiolates generate
      bioactive NO in physiological fluids truly spontaneously (i. e., without
      metabolism or redox activation), with reliable half-lives ranging from 2 seconds
      to 20 hours depending on the ion's structure. They are generally simple-to
      prepare solids with excellent shelf life and high NO content - up to 40% by
      weight. Very importantly from the pharmaceutical point of view, the ionic
      diazeniumdiolates can be easily derivatized to prodrug forms that can be
      activated for NO release enzymatically, photolytically, or by slowed hydrolysis,
      allowing for rational design of strategies for targeting pharmacological delivery
      of NO to sites of need without unwanted collateral exposure of other NO-sensitive
      compartments. In addition to their world-wide sale for use in probing the
      chemical biology of NO, published proof-of-concept studies with diazeniumdiolates
      suggest several more lucrative applications. These include: converting existing
      drugs and biologicals to NO-releasing form to improve performance and/or extend
      patent life; diazeniumdiolating medical devices for improved biocompatibility;
      anticancer drug discovery; use as surgical aids and for wound repair; field
      generation of NO gas; and non-medical uses such as extending the post-harvest
      life of cut flowers. Future work aimed at exploiting the full clinical potential
      of diazeniumdiolate technology will be pursued in this laboratory and strongly
      encouraged in others, with a concurrent fundamental research effort to broaden
      the knowledge base from which further opportunities can be inferred [e. g.,
      exploiting the very recent finding that some diazeniumdiolates appear to offer a
      versatile platform from which nitroxyl (HNO)-generating prodrugs can be
      developed].

PMID- 16101425
TI  - Photosensitive precursors to nitric oxide.
AB  - The photochemistry and use of recently developed photosensitive precursors to
      nitric oxide (NO) are reviewed. As "caged NO" donors these precursors are able to
      deliver NO in a spatially and temporally controllable manner. These properties
      have made such precursors useful in applications in biology and medicine,
      especially in elucidating neurophysiological roles of NO and in new cancer
      therapies.

PMID- 16101426
TI  - Donors of HNO.
AB  - Recent comparisons of the pharmacological effects of nitric oxide (NO) and
      nitroxyl (HNO) donors have demonstrated that the responses to these redox-related
      nitrogen oxides are nearly universally dissimilar. These analyses have suggested
      the existence of mutually exclusive signaling pathways as a result of discrete
      chemical interactions of HNO and NO with a variety of critical biomolecules.
      Although the mechanisms of action are currently unresolved, the pharmacological
      responses to HNO are promising for clinical treatment of cardiovascular diseases
      such as heart failure, myocardial infarction and stroke. This review provides a
      detailed discussion of the most commonly utilized donors of HNO as well as a
      guideline for the characterization of novel donors.

PMID- 16101427
TI  - N-hydroxyurea and acyl nitroso compounds as nitroxyl (HNO) and nitric oxide (NO)
      donors.
AB  - Hydroxyurea has emerged as a new therapy for sickle cell disease but a complete
      mechanistic description of its beneficial actions does not exist. Patients taking
      hydroxyurea show evidence for the in vivo conversion of hydroxyurea to nitric
      oxide (NO), which also has drawn interest as a sickle cell disease treatment.
      While the chemical oxidation of hydroxyurea produces NO or NO-related products,
      NO formation from the reactions of hydroxyurea and hemoglobin do not occur fast
      enough to account for the observed increases in patients taking hydroxyurea. Both
      horseradish peroxidase and catalase catalyze the rapid formation of nitric oxide
      and nitroxyl (HNO) from hydroxyurea. In these reactions, hydroxyurea is converted
      to an acyl nitroso species that hydrolyzes to form HNO. The ferric heme protein
      then oxidizes HNO to NO that combines with the heme iron to form a ferrous-NO
      complex that may act as an NO donor. In general, acyl nitroso compounds,
      regardless of the method of their preparation, hydrolyze to form HNO and the
      corresponding carboxylic acid derivative. Similarly, the incubation of blood and
      hydroxyurea with urease rapidly form NO-related species suggesting the initial
      urease-mediated hydrolysis of hydroxyurea to hydroxylamine, which then reacts
      quickly with hemoglobin to form these products. These studies present two NO
      releasing mechanisms from hydroxyurea that are kinetically competent with
      clinical observations.

PMID- 16101428
TI  - Hydroxyimine NO-donors; FK409 and derivatives.
AB  - FK409 was discovered during a screening program for prostaglandin like compounds
      from microbial products by measuring inhibition of platelet aggregation and
      vasodilation. FK409, a semisynthetic compound derived from acidic nitrosation of
      microbial broth, was shown to be a potent vasodilator with a similar
      pharmacological profile to organic nitrates such as nitroglycerin (NTG). FK409
      dilated the larger diameter coronary vascular vessels more potently than those
      with a smaller diameter in vitro, and was more potent than NTG in a dog angina
      pectoris model. Clinical development of FK409 for angina pectoris included a
      preliminary open efficacy study in about twenty patients with angina pectoris
      showing an improvement in 60-70 % of patients. Anemia proved a drug related
      adverse event. A new study was carried out on around 20 patients with ischemic
      heart disease, but in the longer term the anemia remained. It was concluded that
      FK409 had a comparable efficacy to organic nitrates, but an undesirable adverse
      effect, and development was terminated. Back-up compounds for FK409, explored
      improvement of the pharmacokinetic profile: an increase in duration of action and
      a reduction of the risk of anemia. The pharmacological action of FK409 was
      associated with increased cGMP levels in aortic smooth muscle; and release of NO
      was observed by physicochemical methods. Synthesis of chemically more stable
      derivatives of FK409 with slower NO release was aimed at longer pharmacokinetic
      profiles and a lower incidence of anemia. FR144220 and FR146881 were identified
      as chemically more stable compounds with a longer duration of pharmacological
      action.

PMID- 16101429
TI  - C-nitroso compounds: synthesis, physicochemical properties and biological
      activities.
AB  - Because of the chemical and physical properties of nitric oxide, its effective
      use and delivery for therapeutic application represents a significant challenge.
      Accordingly, current understanding of nitric oxide biology largely stems from the
      use of nitric oxide prodrugs and adducts whose biological activities are based on
      their ability to release nitric oxide or a redox-related species. Among the
      structurally diverse ensemble of nitric oxide donor compounds reported to date
      are the C-nitroso compounds. These compounds have only recently been investigated
      with respect to their potential as nitric oxide donors, although they have been
      known and studied for over 120 years. Here, we consider the synthesis and physico
      chemical properties of the C-nitroso compounds and the available data regarding
      their biological activities. Synthetic methods reviewed include direct
      substitution of H by NO, oxidative approaches, and the addition of various oxides
      of nitrogen across multiple bonds. The electronic spectra of C-nitroso compounds
      and the mechanism and thermodynamics of monomer-dimer equilibration are
      described. The physico-chemical and biological properties of two related classes
      of compounds, the diazetine dioxides and the furoxans, are also described.

PMID- 16101430
TI  - Therapeutic potential of nitrate esters of commonly used drugs.
AB  - Organic nitrates, such as nitroglycerin, have been used in clinical practice for
      more than one century for the treatment of angina, even before the identification
      of Nitric Oxide (NO) as the so-called Endothelium Derived Relaxing Factor (EDRF).
      Recently, multiple functions of this molecule in biology and pathophysiology have
      been discovered and alterations in the NO signalling pathway have often been
      associated with disease progression in mammals, providing a strong rationale for
      the use of NO as a potential drug. To have a therapeutic benefit from NO
      properties, an elegant approach has been designed coupling well-known existing
      drugs with moieties able to slowly release NO following enzymatic metabolism.
      "Hybrid nitrates", in which activities of both the native drug and NO are
      present, have been obtained with the aim of originating safer and more active
      drugs. The technology consists in the choice of the appropriate chemical spacer
      arm carrying the nitric ester in order to obtain the best pharmacodynamic and
      pharmacokinetic profile. The connecting linkers already explored are of different
      chemical structure, ranging from aliphatic chains to heteroaromatic rings. The
      molecules so far obtained have already demonstrated their potential therapeutic
      interest in both pharmacological tests and clinical trials. In this review, we
      describe the approach and the possibility of generating new chemical entities,
      combining well-known drugs with an NO-donating moiety in order to increase
      activity and safety, along with examples of their activity and potential
      therapeutic application in different pathologies. A few significant examples of
      molecules in the early preclinical stage, as well as in advanced clinical
      development will be described.

PMID- 16101431
TI  - N-hydroxyguanidines as substrates of nitric oxide synthases.
AB  - Nitric oxide (NO) has been implicated in a wide variety of disease states. Both
      inhibitors and substrates of nitric oxide synthase (NOS) could have great
      therapeutic potential in the treatment of these diseases. There is considerable
      pharmacological interest in developing inhibitors of NOS, and hundreds of
      inhibitors have been identified. In contrast, the study on NOS substrates is less
      active. The advances in the identification, design and development of NOS
      substrates are discussed in this review. The focus is the chemistry and
      biochemistry of N-hydroxyguanidines. The crystal structures of substrates bound
      to NOSs and the mechanisms of NOS catalyzed NO generation from substrates are
      also discussed.

PMID- 16101432
TI  - Plasmon resonance methods in GPCR signaling and other membrane events.
AB  - The existence of surface guided electromagnetic waves has been theoretically
      predicted from Maxwell's equations and investigated during the first decades of
      the 20th century. However, it is only since the late 1960's that they have
      attracted the interest of surface physicists and earned the moniker of "surface
      plasmon". With the advent of commercially available instruments and well
      established theories, the technique has been used to study a wide variety of
      biochemical and biotechnological phenomena. Spectral response of the resonance
      condition serves as a sensitive indicator of the optical properties of thin films
      immobilized within a wavelength of the surface. This enhanced surface sensitivity
      has provided a boon to the surface sciences, and fosters collaboration between
      surface chemistry, physics and the ongoing biological and biotechnological
      revolution. Since then, techniques based on surface plasmons such as Surface
      Plasmon Resonance (SPR), SPR Imaging, Plasmon Waveguide Resonance (PWR) and
      others, have been increasingly used to determine the affinity and kinetics of a
      wide variety of real time molecular interactions such as protein-protein, lipid
      protein and ligand-protein, without the need for a molecular tag or label. The
      physical-chemical methodologies used to immobilize membranes at the surface of
      these optical devices are reviewed, pointing out advantages and limitations of
      each method. The paper serves to summarize both historical and more recent
      developments of these technologies for investigating structure-function aspects
      of these molecular interactions, and regulation of specific events in signal
      transduction by G-protein coupled receptors (GPCRs).

PMID- 16101433
TI  - The family of Serratia type pore forming toxins.
AB  - The Serratia marcescens hemolysin represents the prototype of a growing family of
      pore forming toxins. The available bacterial genome sequences reveal Serratia
      hemolysin homologues in additional species. However, only S. marcescens hemolysin
      has been studied in great molecular detail. This family of toxins has nothing in
      common with the pore forming toxins of E. coli type (RTX toxins), the
      Staphylococcus aureus alpha-toxin or the thiol activated toxin of group A beta
      hemolytic streptococci (Streptolysin O). Studies on erythrocytes, eukaryotic
      cells and artificial black lipid membranes, have shown that the mechanism of pore
      formation of ShlA is different form other pore forming toxins. The S. marcescens
      hemolysin proteins ShlB and ShlA, exhibit protein sequence homologues in Proteus
      mirabilis, Haemophilus ducreyi, Yersinia pestis, Yersinia enterocolitica,
      Edwardsiella tarda, Photorhabdus luminescens and Xylella fastidiosa . The family
      of Serratia type pore forming toxins show a unique secretory mechanism which has
      been described as a two partner secretion system (TPSS) or type V-secretion
      system. Not only Serratia type pore forming toxins are secreted via TPSS but also
      adhesins from Bordetella pertussis, Erwinia chrysanthemi and Haemophilus
      influenzae. The uniqueness of the Serratia family is underlined by the fact that
      activation of ShlA by ShlB strictly requires phosphatidylethanolamine as a
      cofactor. And, quite unusual, ShlA undergoes a conformational change during
      activation.

PMID- 16101434
TI  - The renin-angiotensin system in the mammalian central nervous system.
AB  - The brain renin-angiotensin system enables the formation of different biological
      active forms of angiotensins within the brain. All enzymes and peptides necessary
      for the biosynthesis of these angiotensins have been recognized within the
      central nervous system. Since there are considerable mismatches concerning the
      localization of the different enzymes, this system is not fully understood.
      Moreover, since alternative pathways of the angiotensin biosynthesis exists,
      localization and generation, especially of the short forms of biologically active
      angiotensins, are largely enigmatic. The brain renin-angiotensin system mediates
      several classic physiological effects including body water balance, maintenance
      of blood pressure, sexual behaviors, and regulation of pituitary gland hormones.
      Beside these classic functions, the brain renin-angiotensin system has more
      subtle functions involving complex mechanisms such as learning and memory. The
      mechanisms of action seem to differ depending on the utilized different bioactive
      angiotensin fragments, which are formed by the action of a variety of enzymes.
      This phenomenon appears to represent an important mechanism for neuromodulation.
      Moreover, there is evidence to suggest that the renin-angiotensin system is
      involved in neurological disorders, as e.g. Alzheimer's or Parkinson's disease.

PMID- 16101435
TI  - Secretoneurin: a new player in angiogenesis and chemotaxis linking nerves, blood
      vessels and the immune system.
AB  - Secretoneurin (SN) represents a 33 amino acid neuropeptide, which is highly
      conserved between mammals, reptiles, birds, amphibians and fish. It is
      specifically expressed in endocrine, neuroendocrine and neuronal tissues. In
      brain, the pattern of SN expression is widespread and unique, partially
      overlapping with established neurotransmitters. ProSN, the precursor protein,
      also named secretogranin II, belongs to a class of proteins collectively called
      chromogranins. Changes in ProSN mRNA, which is significantly regulated by cell
      depolarisation, represent a useful marker for both rapid and long-lasting changes
      (positive and negative) of neuronal activity. Under pathophysiological
      conditions, especially following cellular hypoxia, SN expression can be induced
      in non-endocrine tissues like muscle cells, pneumocytes or tumor epithelial
      cells. Several biological effects were attributed to SN. SN releases dopamine
      from rat striatal slices in a dose dependent manner and influences neurite
      outgrowth in the developing cerebellum. It potently and specifically attracts
      monocytes, eosinophils and endothelial cells towards a concentration gradient and
      acts as an angiogenic cytokine comparable in potency to VEGF. Thus, SN
      contributes to neurogenic inflammation and might play a role in the (hypoxia
      driven) induction of neo-vascularisation in ischemic diseases like peripheral or
      coronary artery disease, diabetic retinopathia, cerebral ischemia or in solid
      tumors. The signalling pathways of various biological effects have not been
      identified in detail, but most data point to a G-protein coupled receptor
      structure with respective associated intracellular events.

PMID- 16101436
TI  - Imaging proteins with atomic force microscopy: an overview.
AB  - Atomic force microscopy (AFM) has become a common tool for biophysical studies of
      proteins; mainly due its property to perform characterizations near physiological
      conditions. The tertiary and quaternary structures, forces driving folding
      unfolding processes, and secondary structure elements can be studied in their
      native environments allowing high resolution level associated with small
      distortions. This review outlines the operational principles and applications of
      AFM for protein biophysics.

PMID- 16101437
TI  - Regulation of energy balance by peptides: a review.
AB  - Regulation of energy balance consists of two intertwined circuitries: food intake
      - metabolic rate--body weight, vs. metabolic rate--heat loss--body temperature.
      Metabolic rate serves interaction between the two. Some peptides influence
      individual components of energy homeostasis, without having coordinated anabolic
      or catabolic properties. Anabolic and catabolic peptides function with
      redundancy, and also show specific features. They all influence ingestive
      behavior vs. metabolic rate and temperature, but do not necessarily act directly
      at central thermoregulatory pathways. Most of them alter metabolic rate (but not
      heat loss) through the ventromedial nucleus, while consequent moderate changes in
      thermal signals can influence function of the preoptic/anterior hypothalamic
      region and initiate compensating regulatory steps to restore temperature. Thus,
      besides ingestion, these peptides influence metabolic rate, whereas the passive
      temperature changes will only be obvious as long as environmental circumstances
      allow. Other substances cause coordinated central regulatory changes resembling
      fever (e.g. cholecystokinin), anapyrexia, or cold-defense: they primarily affect
      body temperature, and then the temperature-dependent changes in
      catabolic/anabolic peptide functions alter feeding behavior. Such arrangement can
      secure relative independence of the two regulatory circles, allowing for
      minimization of depression in metabolic rate and body temperature during
      starvation (despite elevated anabolic activity), or for increased food intake
      with lack of hypothermia in cold adaptation (despite high anabolic activity), or
      for normal body temperature in overfed states (despite enhanced catabolic
      activity), etc. However, the independence is relative since the two systems
      interact in the overall regulation of energy homeostasis: neuropeptides influence
      body temperature and temperature modifies peptide actions.

PMID- 16101439
TI  - DNA drug design for cancer therapy.
AB  - DNA (antisense and other oligonucleotides) drug design represents a direct
      genetic approach for cancer treatment. Such an approach takes advantage of
      mechanisms that activate genes known to confer a growth advantage to neoplastic
      cells. The ability to block the expression of these genes allows exploration of
      normal growth regulation. Progress in DNA drug technology has been rapid, and the
      traditional antisense inhibition of gene expression is now viewed on a genomic
      scale. This global view has led to a new vision in antisense technology, the
      elimination of nonspecific and undesirable side effects, and ultimately the
      generation of more effective and less toxic nucleic acid medicines. Several
      antisense oligonucleotides are in clinical trials, are well tolerated, and are
      potentially active therapeutically. DNA drugs are promising molecular medicines
      for treating human cancer in the near future.

PMID- 16101440
TI  - Oligonucleotides as anticancer agents: from the benchside to the clinic and
      beyond.
AB  - Prevention, improved screening, and better treatment regimens have improved
      cancer incidence and mortality in the last decade. Chemoradiation continues to
      cause high morbidity in patients undergoing treatment. DNA therapeutics have the
      potential to modify the genes that cause tumor progression in order to produce a
      response that is tumor-specific, efficacious and systemic without toxicity to
      normal cells. The most widely used and most experimentally advanced DNA
      therapeutic is the antisense oligonucleotide. These oligomers are predominantly
      used to inhibit mRNA expression. For cancer chemotherapy, the Bcl-2 antisense
      oligonucleotide is currently in phase III clinical trials. Transcription factor
      decoys form DNA:protein heteroduplexes and produce cellular responses at the
      genomic rather than transcriptional level. The use of other transcription factor
      decoys as oncologic reagents is now being developed. The phenomenon of RNA
      interference has only recently been discovered to occur in plants as a response
      to viral infection. Small interfering RNAs cause mRNA inhibition. siRNAs also
      inhibit expression of mRNA, however the intracellular cascade is quite different.
      siRNA could prove to be more powerful and longer lasting than antisense. Several
      DNA therapeutics are currently being studied. This review will focus on antisense
      oligonucleotides, transcription factor decoys and siRNA with an emphasis on how
      they can be employed as anticancer agents. Mechanism of action and design
      strategies will be summarized, as well as therapeutic targets and demonstrated
      clinical efficacy for each reagent.

PMID- 16101441
TI  - Rational drug design of G-quartet DNA as anti-cancer agents.
AB  - The ability of certain DNA sequences to form G-quartet structures has been
      exploited recently to develop novel anti-cancer agents including small molecules
      that promote G-quartet formation within the c-MYC promoter thereby repressing c
      MYC transcription and introducing G-quartet-forming oligodeoxynucleotides (GQ
      ODN) into cancer cells resulting in p53-dependent cell cycle arrest and
      inhibition of DNA replication. GQ-ODNs also have been developed as potent
      inhibitors of signal transducer and activator of transcription (STAT) 3, a
      critical mediator of oncogenic signaling in many cancers. This review summarizes
      the rational design of G-quartet forming DNA drugs as Stat3 inhibitors. Topics
      that are reviewed include the strategy of structure-based drug design,
      establishment of a structure-activity relationship, development of a novel
      intracellular delivery system for G-quartet-forming DNA agents and in vivo drug
      testing to assess the anti-cancer effects of DNA drugs in tumor xenografts.
      Results to date with GQ-ODN targeting Stat3 are encouraging, and it is hoped that
      continued pursuit of the methodology outlined here may lead to development of an
      effective agent for treatment of metastatic cancers, such as prostate and breast,
      in which Stat3 is constitutively activated.

PMID- 16101442
TI  - Targeting chk2 kinase: molecular interaction maps and therapeutic rationale.
AB  - Most anticancer drugs presently used clinically target genomic DNA. The
      selectivity of these anticancer drugs for tumor tissues is probably due to tumor
      specific defects suppressing cell cycle checkpoints and DNA repair, and enhancing
      apoptotic response in the tumor. We will review the molecular interactions within
      the ATM-Chk2 pathway implicating the DNA damage sensor kinases (ATM, ATR and DNA
      PK), the adaptor BRCT proteins (Nbs1, Brca1, 53BP1, MDC1) and the effector
      kinases (Chk2, Chk1, Plk3, JNK, p38). The molecular interaction map convention
      (MIM) will be used for presenting this molecular network
      (http://discover.nci.nih.gov/mim/). A characteristic of the ATM-Chk2 pathway is
      its redundancy. First, ATM and Chk2 phosphorylate common substrates including
      p53, E2F1, BRCA1, and Chk2 itself, which suggests that Chk2 (also known as
      CHECK2, Cds1 in fission yeast, and Dmchk2 or Dmnk or Loki in the fruit fly) acts
      as a relay for ATM and/or as a salvage pathway when ATM is inactivated. Secondly,
      redundancy is apparent for the substrates, which can be phosphorylated/activated
      at similar residues by Chk2, Chk1, and the polo kinases (Plk's). Functionally,
      Chk2 can activate both apoptosis (via p53, E2F1 and PML) and cell cycle
      checkpoint (via Cdc25A and Cdc25C, p53, and BRCA1). We will review the short list
      of published Chk2 inhibitors. We will also propose a novel paradigm for screening
      interfacial inhibitors of Chk2. Chk2 inhibitors might be used to enhance the
      tumor selectivity of DNA targeted agents in p53-deficient tumors, and for the
      treatment of tumors whose growth depends on enhanced Chk2 activity.

PMID- 16101443
TI  - Targeting transcription factors for cancer therapy.
AB  - Advances in the molecular biology of oncogenesis have established a key role for
      transcription factors in malignant transformation. In some cases the activity of
      the transcription factor itself is altered by mutation. In many other cases, the
      activity of the transcription factor is affected by mutations in upstream
      signaling or regulatory proteins. This review highlights four transcription
      factors--Stat3, Stat5, NF-kappaB, and HIF-1--which are associated with cancer
      development. The evidence for the involvement of these factors in oncogenesis is
      reviewed. Further, we examine the efforts to specifically target these
      transcription factors for therapeutic intervention. Such strategies include using
      peptidomimetics, antisense oligonucleotides, small molecule inhibitors, and G
      quartet oligonucleotides. Inhibition of transcription factor activity may occur
      at the level of activation, translocation, or DNA binding. Application of these
      approaches to in vitro and in vivo models of tumorigenesis is discussed.

PMID- 16101444
TI  - Synthetic oligodeoxynucleotides containing deoxycytidyl-deoxyguanosine
      dinucleotides (CpG ODNs) and modified analogs as novel anticancer therapeutics.
AB  - Oligodeoxynucleotides containing deoxycytidyl-deoxyguanosine dinucleotides (CpG
      ODNs) activate the host immune system, leading to innate and acquired immune
      responses. The immune stimulatory effects of CpG ODNs are being exploited as a
      novel therapeutic approach to treatment of human diseases, and some CpG ODNs are
      being evaluated in clinical trials. The cellular recognition of CpG motifs
      requires the presence of the Toll-like receptor (TLR) 9, which triggers cell
      signaling and immune responses. There are three main types of first-generation
      CpG ODNs, which mimic the immunostimulatory activity of bacterial DNA and are
      recognized by TLR9, A-, B- and C-Class ODNs. Although all three CpG ODN classes
      stimulate TLR9-dependent signaling, there are striking differences in the cell
      types they activate and their dose-dependent immunostimulatory efficacy. Second
      generation CpG ODNs, with advanced nucleic acid chemistry and unique
      modifications to their sequences and structures are being developed. Medicinal
      chemistry studies suggest that the immunomodulatory activity of CpG ODNs can be
      altered by site-specific incorporation of modifications in order to develop
      disease-specific drugs. Both first- and second-generation CpG ODNs have potential
      for treatment of various human diseases, such as infections, immunodeficiencies,
      and cancers. This article will focus on the recent advances in developing CpG
      ODNs as novel anti-cancer therapeutic agents.

PMID- 16101445
TI  - Bacterial toxins: potential weapons against HIV infection.
AB  - Natural toxins are the product of a long-term evolution, and have captured
      crucial events in the most essential and vital processes of living organisms.
      They can attack components of the protein synthesis machinery (as in the case of
      Diphteria and Shiga toxins, and Ribosome inactivating proteins), actin
      polymerization (Clostridium botulinum type C, C2, toxins and Enterotoxin A),
      signal transduction pathways (Cholera toxin, Heat-labile enterotoxins, Pertussis
      and Adenylate cyclase toxins), intracellular trafficking of vesicules (for
      Tetanus and Botulinum neurotoxin type C) as well as immune and/or inflammatory
      responses (Pyrogenic exotoxins, Cholera and Pertussis toxins). Of interest is the
      fact that several bacterial and vegetal toxins can either kill selectively cells
      infected with the human immunodeficiency virus (HIV) or exert inhibitory effects
      on its life cycle. In particular both pertussis toxin (PTX) and its nontoxic B
      oligomeric component (PTX-B) can block the infectious process in vitro at
      multiple levels, by preventing the entry of CCR5-dependent (R5) HIV strains and
      by inhibiting both R5 and CXCR4-dependent HIVs at post-entry level(s). In
      addition, some toxins possess immunostimulating properties that have been
      exploited in terms of adjuvancy and induction of specific cytotoxic T lymphocytes
      responses to different vaccine preparations, including some experimental vaccine
      against HIV infection. Thus, toxins may represent a relatively unexplored
      exhibition of powerful biological agents that could either prevent infection or
      attack HIV-infected cells.

PMID- 16101446
TI  - Ex vivo gene transfer for improvement of transplanted pancreatic islet viability
      and function.
AB  - Human pancreatic islet transplantation has recently been shown to be successful
      in replacing pancreatic endocrine function into type 1 diabetic recipients. A
      major drawback, however, is the high amount of pancreatic ss cells required to
      render one single patient insulin-independent. Given the shortage of human beta
      cell donors, the majority of type 1 diabetic patients remain excluded from this
      therapeutic option. High number of islets are requested since substantial islet
      cell death and dysfunction occur within the first few hours and days after islet
      transplantation. Impaired vascularization of the engraft, the non-specific
      inflammatory reaction at the site of transplantation, together with the presence
      of active or memory autoimmune responses to islet autoantigens and allogeneic
      recognition contribute to apoptosis of ss cells and subsequent early graft
      function loss. This review will focus on ex vivo engineering of the islet graft
      by gene transfer to improve islet engraftment. An overview of currently used gene
      transfer techniques will be given and their potential will be discussed.

PMID- 16101448
TI  - Mechanism of local anesthetic drug action on voltage-gated sodium channels.
AB  - Local anesthetic drugs interfere with excitation and conduction by action
      potentials in the nervous system and in the heart by blockade of the voltage
      gated Na channel. Drug affinity varies with gating state of the channel. The
      drugs show low affinity at slow excitation rates, but high affinity when the
      channels are opened and inactivated during action potentials at high frequency,
      as they are during pain or during a cardiac arrhythmia. The drugs are thought to
      access their binding site in the inner pore by passage through the membrane and
      entry through the inner pore vestibule. There have been three major developments
      in the last decade that greatly increase our understanding of their mechanism of
      action. Firstly, amino acid residues critical to drug binding have been located
      by mutagenesis, and it is possible to develop a molecular model of the drug
      binding site. Secondly, a path for drug access directly from the outside has been
      characterized in the cardiac isoform of the channel. Thirdly, the hypothesis that
      high affinity binding stabilizes the fast inactivated conformation of the channel
      has been challenged. Rather, the drug may stabilize a slow inactivated state and
      immobilize the voltage sensor in domain III in its activated outward position.
      The combination of mutational study of the cloned Na channels and patch clamp
      offers the opportunity to understand the detailed molecular mechanism of drug
      action and to resolve drug structure-function.

PMID- 16101449
TI  - Activation and activators of TRPV1 and their pharmaceutical implication.
AB  - TRPV1 is a channel expressed highly in small sensory neurons. TRPV1 is a ligand
      gated, cation channel that is activated by heat, acid and capsaicin, a principal
      ingredient in hot peppers. Because of its possible role as a polymodal molecular
      detector, TRPV1 is studied most extensively. In mice lacking TRPV1, thermal
      hyperalgesia induced by inflammation is reduced, suggesting a role for mediating
      inflammatory pain. Activity of TRPV1 is modulated by actions of various kinases
      such as protein kinase A and C. Furthermore, phosphorylation by Ca(2+)-calmodulin
      dependent kinase II is required for its ligand binding. TRPV1 is activated by
      various endogenous lipids, such as anandamide, N-arachidonoyl-dopamine, and
      various metabolic products of lipoxygenases. 12-hydroperoxyeicosatetraenoic acid,
      an immediate metabolic product of 12-lipoxygenase, activates TRPV1 and shares 3
      dimensional structural similarity with capsaicin. Because lipoxygenase products
      can activate TRPV1 in sensory neurons, upstream signals to lipoxygenase/TRPV1
      pathway have been questioned. Indeed, bradykinin, a potent pain-causing
      substance, is now known to activate TRPV1 via lipoxygenase pathway. However, we
      cannot overlook the sensitizing effect of bradykinin via the phospholipase C or
      protein kinase C pathway. Interestingly, histamine, a pruritogenic substance,
      also appears to use the lipoxygenase/TRPV1 pathway in order to excite sensory
      neurons. Because of its role in the mediation of nociception, antagonists of
      TRPV1 are targeted for development of potential analgesics. In the present
      review, theoretical background of organic synthesis of SC0030, a potent
      antagonist of TRPV1 is presented.

PMID- 16101450
TI  - Insulin secretagogues, sulfonylurea receptors and K(ATP) channels.
AB  - ATP-sensitive K+ channels, termed K(ATP) channels, provide a link between
      cellular metabolism and membrane electrical activity in a variety of tissues.
      Channel isoforms have been identified and are targets for compounds that both
      stimulate and inhibit their activity resulting in membrane hyperpolarization and
      depolarization, respectively. Examples include relaxation of vascular smooth
      muscle and stimulation of insulin secretion. This article reviews the cloning,
      molecular biology, and structure of K(ATP) channels, with particular focus on the
      SUR1/K(IR)6.2 neuroendocrine channels that are important for the regulation of
      insulin secretion. We integrate the extensive pharmacologic structure-activity
      relationship data on these channels, which defines a bipartite drug binding
      pocket in the SUR (sulfonylurea receptor), with recent structure-function studies
      that identify domains of SUR and K(IR)6.2, the channel pore, which are critical
      for channel assembly, for gating, and for the ligand-receptor interactions that
      modulate channel activity. The atomic structure of a sulfonylurea in a protein
      pocket is used to develop insight into the recognition of these compounds. A
      homology model of K(ATP) channels, based on VC-MsbA, another member of the ABC
      protein family, is described and used to position amino acids important for the
      action of channel openers and blockers within the core of SUR. The model has a
      central chamber which could serve as a multifaceted binding pocket.

PMID- 16101451
TI  - Physiology and pharmacology of two-pore domain potassium channels.
AB  - Searching the DNA database has led to the identification of a class of K+
      channels now referred to as two-pore or tandem-pore domain K+ (K2P) channels. The
      K2P channel is structurally unique in that each subunit possesses two pore
      forming domains and four transmembrane segments. In mammals, sixteen K2P channel
      genes have been identified, and their mRNA transcripts are expressed in many
      different cell types and tissues. K2P channels have properties of background or
      leak K+ channels, and therefore play a crucial role in setting the resting
      membrane potential and regulating cell excitability. Some K2P channels are
      activated by certain physical and chemical factors such as lipids, volatile
      anesthetics, heat, oxygen, protons and membrane tension. Some K2P channels are
      targets of agonists that bind receptors coupled to different types of G proteins,
      and are probably involved in a variety of neurotransmitter and peptide hormone
      mediated signal transduction processes. Such diverse properties of K2P channels
      suggest that they are involved in many different physiological and
      pathophysiological processes. Therefore, K2P channels could become potentially
      important therapeutic targets for the treatment of various pathological
      conditions.

PMID- 16101452
TI  - Ion channel defects in idiopathic epilepsies.
AB  - Idiopathic epilepsies are genetically determined diseases of the central nervous
      system characterized by typical epileptic seizures and EEG abnormalities but not
      associated with structural brain lesions. In recent years, an increasing number
      of mutations associated with idiopathic epilepsy syndromes were identified in
      genes encoding subunits of voltage- or ligand-gated ion channels. These
      encouraging results provide a plausible pathophysiological concept, since ion
      channels form the basis for neuronal excitability and are the major targets for
      anticonvulsive pharmacotherapy. The first epilepsy genes were identified for rare
      autosomal dominant syndromes within large pedigrees. Recently, a few mutations
      were also found for the frequent classical forms of idiopathic generalized
      epilepsies (IGE), for example absence or juvenile myoclonic epilepsy. The
      mutations can affect ion channels which on one hand have been known since several
      decades to be crucial for neuronal function, such as the voltage-gated sodium
      channel or the GABA(A) receptor, or on the other hand were newly identified
      within the last decade as KCNQ potassium channels or the ClC-2 chloride channel.
      Functional studies characterizing the molecular defects of the mutant channels
      point to a central role of GABAergic synaptic inhibition in the pathophysiology
      of IGE. Furthermore, newly discovered genes may be suitable as novel targets for
      pharmacotherapy such as KCNQ channels for the anticonvulsant drug retigabine.
      Altogether, these genetic and pathophysiological investigations will enhance our
      knowledge about the understanding of epileptogenesis and can help to improve
      anticonvulsive therapy.

PMID- 16101453
TI  - Intracellular chloride channels: critical mediators of cell viability and
      potential targets for cancer therapy.
AB  - The passage of ions to form and maintain electrochemical gradients is a key
      element for regulating cellular activities and is dependent on specific channel
      proteins or complexes. Certain ion channels have been the targets of
      pharmaceuticals that have had impact on a variety of cardiovascular and
      neurological diseases. Chloride channels regulate the movement of a major
      cellular anion, and in so doing they in part determine cell membrane potential,
      modify transepithelial transport, and maintain intracellular pH and cell volume.
      There are multiple families of chloride channel proteins, and respiratory,
      neuromuscular, and renal dysfunction may result from mutations in specific family
      members. Interest in chloride channels related to cancer first arose when the
      multidrug resistance protein (MDR/P-glycoprotein) was linked to volume-activated
      chloride channel activity in cancer cells from patients undergoing chemotherapy.
      More recently, CLC, CLIC, and CLCA intracellular chloride channels have been
      recognized for their contributions in modifying cell cycle, apoptosis, cell
      adhesion, and cell motility. Moreover, advances in structural biology and high
      throughput screening provide a platform to identify chemical compounds that
      modulate the activities of intracellular chloride channels thereby influencing
      chloride ion transport and altering cell behavior. This review will focus on
      several chloride channel families that may contribute to the cancer phenotype and
      suggest how they may serve as novel targets for primary cancer therapy.

PMID- 16101454
TI  - The TRPM cation channels in the immune context.
AB  - The molecular identification of novel ion channels expressed in the immune
      context provides very attractive potential targets for new therapeutic drugs
      designed to modulate immune system function. Several members of the recently
      discovered TRPM family of cation channels are expressed in immune cells. The TRPM
      channels show an astonishing diversity regarding their gating mechanisms and
      permeability profiles. First functional studies demonstrate that this diversity
      correlates with the range of potential biological processes TRPM channels might
      be involved in. Even though this field of research is still in its infancy, new
      insights into the regulation of ion homeostasis in immune cells start to emerge.
      An overview of the current knowledge about the TRPM family members in general,
      and in the immune context in particular, will be given throughout this review.

PMID- 16101455
TI  - Beyond single pathway inhibition: MEK inhibitors as a platform for the
      development of pharmacological combinations with synergistic anti-leukemic
      effects.
AB  - The MEK/MAPK signaling module is a key integration point along signal
      transduction cascades that regulate cell growth, survival, and differentiation,
      and is aberrantly activated in many human tumors. In tumor cells, constitutive
      MAPK activation affords increased proliferation and resistance to apoptotic
      stimuli, including classical cytotoxic drugs. In most instances, however, MAPK
      inhibition has cytostatic rather than cytotoxic effects, which may explain the
      lack of objective responses observed in early clinical trials of MEK inhibitors.
      Nevertheless, amenability of the MAPK pathway to pharmacodynamic evaluation and
      negligible clinical toxicity make MEK inhibitors an ideal platform to build
      pharmacological combinations with synergistic antitumor activity. In AML, the
      MEK/MAPK pathway is constitutively activated in the majority of cases (75%),
      conferring a uniformly poor prognosis; in preclinical models of AML, MEK blockade
      profoundly inhibits cell growth and proliferation and downregulates the
      expression of several anti-apoptotic players, thereby lowering the apoptotic
      threshold. Apoptosis induction, however, requires concentrations of MEK
      inhibitors much higher than those required to inhibit proliferation.
      Nevertheless, MEK blockade efficiently and selectively sensitizes leukemic cells
      to sub-optimal doses of other apoptotic stimuli, including classical cytotoxics
      (nucleoside analogs, microtubule-targeted drugs, gamma-irradiation), biologicals
      (retinoids, interferons, arsenic trioxide), and, most interestingly, other signal
      transduction/apoptosis modulators (UCN-01, STI571, Bcl-2 antagonists). In most
      instances, these MEK inhibition-based combinations result in a striking pro
      apoptotic synergism in preclinical models. Here we briefly discuss evidence
      suggesting that MAPK pathway inhibition could play a prominent role in the
      development of integrated therapeutic strategies aimed at synergistic anti
      leukemic effects.

PMID- 16101456
TI  - Targeting central plasticity: a new direction of finding painkillers.
AB  - It is well documented that sensory transmission, including pain, receives
      endogenous inhibitory modulatory influences at dorsal horn of the spinal cord.
      Recent results, from behavioral to molecular studies, demonstrate that injury
      caused plastic changes in forebrain areas. In addition to encoding pain, these
      supraspinal areas may also affect pain transmission in the spinal cord level by
      activating "top-down" descending facilitatory systems. In this review, I provide
      review of evidence related to these new progresses, from human brain imaging to
      work from genetically mutant mice.

PMID- 16101458
TI  - Matrix-assisted laser desorption/ionization analysis of non-covalent complexes:
      fundamentals and applications.
AB  - Mass spectrometry is now a well established and powerful method for analysing the
      structure of biomolecules and more recently their non-covalent interactions. It
      is based on two soft ionization techniques, electrospray ionization (ESI) and
      matrix-assisted laser desorption/ionization (MALDI), which allow to produce
      biomolecule ions in gas phase with a very high efficiency for a subsequent
      analysis in the mass analyser. The high sensitivity and the high precision of
      modern mass spectrometry were first applied to elucidate the primary structure of
      proteins in the so-called proteomic area. It is widely used in biological and
      medical sciences. The new challenge for the mass spectrometrist is to decipher
      the quaternary structure of biomolecules by preserving into the gas phase the
      weak interactions that exist between molecules in solution. In this review, we
      will focus on the application of matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) for studying the non-covalent associations. Keeping in
      mind that the weak interactions between partners must be preserved from the
      solution into the gas phase, we will describe the critical parameters involved in
      both the desorption/ionization processes and the target preparation including the
      incorporation of the non-covalent complex into the matrix crystals. Various
      examples will be presented showing that weak interactions can survive the entire
      MALDI process allowing the direct detection of intact complexes. However, all
      these weak interactions cannot be always preserved from the cell to the mass
      spectrometer. Specific methodologies have been developed to get insights of these
      interactions. Most of them will be presented in this review.

PMID- 16101459
TI  - Activated surfaces for laser desorption mass spectrometry: application for
      peptide and protein analysis.
AB  - Thanks to the development of matrix assisted laser desorption/ionisation (MALDI),
      laser desorption based mass spectrometry became an essential method for the
      analysis of biomolecules. This review will discuss the various surface
      modifications used in combination with laser desorption mass spectrometry and
      their application for the analysis of peptides and proteins. In the first hand,
      some modified surfaces are designed to enhance the laser desorption/ionisation
      process; this includes the use of carbon, porous silicon surfaces and also
      immobilised matrix. In an other hand chemical and biochemical modified surfaces
      developed to isolate species with more or less specific interactions can be used
      for on-slide sample clean-up before MALDI-MS analysis. In addition, different
      experimental devices as mass spectrometers and microfluidic devices used for such
      a purpose will be presented.

PMID- 16101460
TI  - Application of MALDI-TOF mass spectrometry in screening and diagnostic research.
AB  - During the last years, mass spectrometry has revolutionised protein biochemistry
      and has advanced to a superior tool for the identification and detailed analysis
      of peptides and proteins. The high throughput allowed by some mass spectrometry
      platforms has enabled the important step from analysis of individual proteins to
      proteomics. Recently, an additional field of mass spectrometry applications has
      emerged - namely screening and diagnostic research. In contrast to protein
      identification, screening applications have to detect analyte molecules of
      defined molecular weights which can be calculated beforehand, for example by
      means of chemical structures. Here, the accuracy and sensitivity of mass
      spectrometry has to be combined with the requirements of high-throughput
      analyses, in particular speed and automation. These criteria are especially
      fulfilled by state of the art matrix-assisted laser desorption/ionisation time-of
      flight mass spectrometry (MALDI-TOF MS) instruments. The first high throughput
      screening (HTS) application proved to be genotyping of single nucleotide
      polymorphisms. The same principle was later applied for several quality control
      issues, for example for oligonucleotides, peptide or compound libraries. This
      development has culminated in the screening and profiling of complex biomarker
      patterns in clinical proteomics to detect a molecular fingerprint for specific
      diseases in biological samples. Thus, mass spectrometry based methods are
      expected to enable a very early diagnosis of diseases with minimally invasive
      methods of investigation. This type of high end screening application has the
      potential to revolutionise the early diagnosis of many diseases. Here, we give an
      overview of the application of mass spectrometry in the fields of screening and
      diagnostic research.

PMID- 16101461
TI  - Nucleic Acid analysis by fourier transform ion cyclotron resonance mass
      spectrometry at the beginning of the twenty-first century.
AB  - Mass spectrometers measure an intrinsic property (i.e., mass) of a molecule,
      which makes it an ideal platform for nucleic acid analysis. Importantly, the
      unparalleled capabilities of Fourier transform ion cyclotron resonance (FT-ICR)
      mass spectrometry further extend its usefulness for nucleic acid analysis. The
      beginning of the twenty-first century has been marked with notable advances in
      the field of FT-ICR mass spectrometry analysis of nucleic acids. Some of these
      accomplishments include fundamental studies of nucleic acid properties,
      improvements in sample clean up and preparation, better methods to obtain higher
      mass measurement accuracy, analysis of noncovalent complexes, tandem mass
      spectrometry, and characterization of peptide nucleic acids. This diverse range
      of studies will be presented herein.

PMID- 16101462
TI  - Glycomics and mass spectrometry.
AB  - Proteomics is closely associated with the modifications of the gene product such
      as the post-translational events that yield functionally active gene products.
      Among these, glycosylation represents a critically important post-translational
      modification and is a target for proteomic research. Glycan moieties are involved
      in a wide variety of intracellular, cell-cell and cell-matrix recognition events.
      This is why understanding how glycosylation affects the activities and functions
      of proteins in health and disease represents a major challenge. The study of the
      glycome--the whole set of glycans produced in a single organism--is therefore
      essential to determine the functions of all genes. Mass spectrometry, in
      combination with modern separation methodologies, is one of the most powerful and
      versatile techniques for the structural analysis of oligosaccharides. This review
      provides a summary of the current knowledge for the mass spectrometric analysis
      of glycoproteins and their glycan structures.

PMID- 16101463
TI  - Focus on the three key enzymes hydrolysing endocannabinoids as new drug targets.
AB  - The family of endocannabinoids (i.e., the endogenous agonists of cannabinoid
      receptors) contains several polyunsaturated fatty acid amides such as anandamide
      (AEA) and oleamide but also esters such as 2-arachidonoylglycerol (2-AG). These
      compounds are the subject of growing interest in pharmacology for their multiple
      therapeutic potentials. Unfortunately, they are rapidly inactivated by enzymatic
      hydrolysis, which prevents their effective medical use. Inhibitors of
      endocannabinoid degradation seem to be necessary tools for the development of
      endocannabinoid therapeutics. But hitting this target is inconceivable without
      good knowledge of the enzymes. Fatty acid amide hydrolase (FAAH) is the oldest
      and the best characterised enzyme involved in the degradation of
      endocannabinoids. Cloning, distribution in the body and crystal structure of FAAH
      have been described. A large number of FAAH inhibitors have also been synthesised
      and tested. For a long time, FAAH was considered as the only key enzyme
      hydrolysing endocannabinoids. But recent findings indicate that at least two
      other enzymes have critical role in the endocannabinoids degradation.
      Monoglyceride lipase participates in 2-AG degradation and some data indicate that
      it is the primary mechanism for 2-AG inactivation in intact neurons. N
      palmitoylethanolamine-selective acid amidase (NPAA) is a second fatty acid amide
      hydrolase more active with N-palmitoylethanolamine, an anti-inflammatory
      substance. The purpose of this review is to collect and compare the catalytic
      properties of these 3 key enzymes hydrolysing endocannabinoids.

PMID- 16101464
TI  - Traveling space: biological considerations, and the benefits for terrestrial
      medicine.

PMID- 16101465
TI  - Benefit of repeated receptor stimulation as a spaceflight medical tool to promote
      cardiovascular fitness: different orthostatic paradigms compared.
AB  - We used various orthostatic stimulus combinations to better understand the
      physiology and countermeasure potential of repeated change of body position in
      humans. The purpose of the investigations reported was threefold: To investigate
      cardiovascular and hormonal effects of repeated transition between partially
      antiorthostatic (-30 degrees HDT) and partially head-up passive body tilt (+30
      degrees HUT). Protocol Y denotes the repeated transition between these two body
      positions; To apply, in the same test persons, repeated transition between supine
      and passive upright (Protocol X), and to compare the effect of the two protocols;
      To find out which stimulus pattern provides the largest physiological effects
      and, hence, presumably the largest countermeasure potential. We chose our tilt
      protocol according to tilt angle sine ranges: The sine difference is 1.0 both in
      Protocol X (sine=0 vs. sine=1.0) and Y (sine= -0.5 vs. sine= +0.5) since this
      difference, and not the angle change per se, determines hydrostatic effect
      intensities. Due to longer-lasting neurohormonal effects elicited by tilting
      procedures, they all should be a useful countermeasure against post
      immobilization orthostatic instability, a conjecture not yet been tested in this
      specific form. Therefore, one of the questions asked in this study were if
      movement between the two defined body positions produces similar changes when
      employing Protocol X vs. Protocol Y.

PMID- 16101466
TI  - Neurovestibular and sensorimotor studies in space and Earth benefits.
AB  - This review summarizes what has been learned from studies of human
      neurovestibular system in weightless conditions, including balance and
      locomotion, gaze control, vestibular-autonomic function and spatial orientation,
      and gives some examples of the potential Earth benefits of this research. Results
      show that when astronauts and cosmonauts return from space flight both the
      peripheral and central neural processes are physiologically and functionally
      altered. There are clear distinctions between the virtually immediate adaptive
      compensations to weightlessness and those that require longer periods of time to
      adapt. However, little is known to date about the adaptation of sensory-motor
      functions to long-duration space missions in weightlessness and to the
      transitions between various reduced gravitational levels, such as on the Moon and
      Mars. Results from neurovestibular research in space have substantially enhanced
      our understanding of the mechanisms and characteristics of postural, gaze, and
      spatial orientation deficits, analogous to clinical cases of labyrinthine
      defective function. Also, space neurosciences research has participated in the
      development and application of significant new technologies, such as video
      recording and processing of three-dimensional eye movements and posture, hardware
      for the unencumbered measurement of head and body movement, and procedures for
      investigating otolith function on Earth. In particular, devices such as
      centrifugation or off-vertical axis rotation could enhance clinical neurological
      testing because it provides linear acceleration which specifically stimulates the
      otolith organs in a frequency range close to natural head and body movement.

PMID- 16101467
TI  - Cardiovascular consequences of weightlessness promote advances in clinical and
      trauma care.
AB  - Cardiovascular adaptations driven by exposure to weightlessness cause some
      astronauts to experience orthostatic intolerance upon return to Earth.
      Maladaptations of spaceflight that lead to hemodynamic instability are temporary,
      and therefore astronauts provide for researchers a powerful model to study
      cardiovascular dysfunction in terrestrial patients. Orthostatic intolerance in
      astronauts is linked to changes in the autonomic control of cardiovascular
      function, and so patients that suffer neurocardiogenic syncope may benefit from a
      greater understanding of the effects of spaceflight on the autonomic nervous
      system. In addition, appropriate autonomic compensation is fundamental to the
      maintenance of stable arterial pressures and brain blood flow in patients
      suffering traumatic bleeding injuries. The application of lower body negative
      pressure (LBNP), an experimental procedure used widely in aerospace physiology,
      induces autonomic and hemodynamic responses that are similar to actual hemorrhage
      and therefore may emerge as a useful experimental tool to simulate hemorrhage in
      humans. Observations that standing astronauts and severely injured patients are
      challenged to maintain venous return has contributed to the development of an
      inspiratory impedance threshold device that serves as a controlled "Mueller
      maneuver" and has the potential to reduce orthostatic intolerance in returning
      astronauts and slow the progression to hemorrhagic shock in bleeding patients. In
      this review, we focus on describing new concepts that have arisen from studies of
      astronauts, patients, and victims of trauma, and highlight the necessity of
      developing the capability of monitoring medical information continuously and
      remotely. Remote medical monitoring will be essential for long-duration space
      missions and has the potential to save lives on the battlefield and in the
      civilian sector.

PMID- 16101468
TI  - Regulation of body fluid and salt homeostasis--from observations in space to new
      concepts on Earth.
AB  - The present manuscript summarizes recent discoveries that were made by studying
      salt and fluid homeostasis in weightlessness. These data indicate that 1. atrial
      natriuretic peptide appears not to play an important role in natriuresis in
      physiology, 2. the distribution of body fluids appears to be tightly coupled with
      hunger and thirst regulation, 3. intrathoracic pressure may be an important co
      regulator of body fluid homeostasis, 4. a so far unknown low-affinity, high
      capacity osmotically inactive sodium storage mechanism appears to be present in
      humans that is acting through sodium/hydrogen exchange on glycosaminoglycans and
      might explain the pathophysiology, e.g., of salt sensitive hypertension. The
      surprising and unexpected data underline that weightlessness is an excellent tool
      to investigate the physiology of our human body: If we knew it, we should be able
      to predict changes that occur when gravity is absent. But, as data from space
      demonstrate, we do not.

PMID- 16101469
TI  - Space exercise and Earth benefits.
AB  - The detrimental impact of long duration space flight on physiological systems
      necessitates the development of exercise countermeasures to protect work
      capabilities in gravity fields of Earth, Moon and Mars. The respective rates of
      physiological deconditioning for different organ systems during space flight has
      been described as a result of data collected during and after missions on the
      Space Shuttle, International Space Station, Mir, and bed rest studies on Earth.
      An integrated countermeasure that simulates the body's hydrostatic pressure
      gradient, provides mechanical stress to the bones and muscles, and stimulates the
      neurovestibular system may be critical for maintaining health and well being of
      crew during long-duration space travel, such as a mission to Mars. Here we review
      the results of our studies to date of an integrated exercise countermeasure for
      space flight, lower body negative pressure (LBNP) treadmill exercise, and
      potential benefits of its application to athletic training on Earth.
      Additionally, we review the benefits of Lower Body Positive Pressure (LBPP)
      exercise for rehabilitation of postoperative patients. Presented first are
      preliminary data from a 30-day bed rest study evaluating the efficacy of LBNP
      exercise as an integrated exercise countermeasure for the deconditioning effects
      of microgravity. Next, we review upright LBNP exercise as a training modality for
      athletes by evaluating effects on the cardiovascular system and gait mechanics.
      Finally, LBPP exercise as a rehabilitation device is examined with reference to
      gait mechanics and safety in two groups of postoperative patients.

PMID- 16101470
TI  - Autonomic neural functions in space.
AB  - Autonomic neural functions are important to regulate vital functions in the
      living body. There are different methods to evaluate indirectly and directly
      autonomic, sympathetic and parasympathetic, neural functions of human body. Among
      various methods, microneurography is a technique to evaluate directly sympathetic
      neural functions in humans. Using this technique sympathetic neural traffic
      leading to skeletal muscles (muscle sympathetic nerve activity; MSNA) can be
      recorded from human peripheral nerves in situ. MSNA plays essentially important
      roles to maintain blood pressure homeostasis against gravity. Orthostatic
      intolerance is an important problem as an autonomic dysfunction encountered after
      exposure of human beings to microgravity. There exist at least two different
      types of sympathetic neural responses, low and high responders to orthostatic
      stress in orthostatic hypotension seen in neurological disorders. To answer the
      question if post-spaceflight orthostatic intolerance is induced by low or high
      MSNA responses to orthostatic stress, MSNA was microneurographically recorded for
      the first time before, during and after spaceflight in 1998 under Neurolab
      international research project. The same activity has been recorded during and/or
      after ground-based short- and long-term simulations of microgravity. MSNA was
      rather enhanced on the 12(th) and 13(th) day of spaceflight and just after
      landing day. Postflight MSNA response to head-up tilt was well preserved in
      astronauts who were orthostatically well tolerant. MSNA was suppressed during
      short-term simulation of microgravity less than 2 hours but was enhanced after
      long-term simulation of microgravity more than 3 days. Orthostatic intolerance
      after exposure to long-term simulation of microgravity was associated with
      reduced MSNA response to orthostatic stress with impaired baroreflex functions.
      These findings obtained from MSNA recordings in subjects exposed to space as well
      as short- and long-term simulations of microgravity indicate that sympathetic
      neural control is lowered when exposed to short-term microgravity but becomes
      enhanced after exposure to long-term microgravity. A lack of enhanced sympathetic
      neural response to orthostatic stress may induce orthostatic intolerance. Based
      on these findings effective countermeasures should be developed to prevent
      autonomic dysfunctions induced by exposure to microgravity. These include
      development of prescription and devices of physical exercise, electrical and
      magnetic nerve stimulations, body vibration, elastic bandage and stocking, lower
      body negative pressure, artificial gravity, medical drugs, and combinations of
      them. These countermeasures will be beneficial to prevent autonomic dysfunctions
      related to gravitational stress such encountered in bedridden subjects as
      orthostatic hypotension, atrophy of antigravity muscles and so on. This is
      particularly important in the present aged-society with many bedridden elderly
      people. The knowledge accumulated from studies on autonomic neural functions in
      space should be very useful to establish effective countermeasures and preventive
      methods for gravity-dependent autonomic dysfunctions.

PMID- 16101471
TI  - Cardiovascular and fluid volume control in humans in space.
AB  - The human cardiovascular system and regulation of fluid volume are heavily
      influenced by gravity. When decreasing the effects of gravity in humans such as
      by anti-orthostatic posture changes or immersion into water, venous return is
      increased by some 25%. This leads to central blood volume expansion, which is
      accompanied by an increase in renal excretion rates of water and sodium. The
      mechanisms for the changes in renal excretory rates include a complex interaction
      of cardiovascular reflexes, neuroendocrine variables, and physical factors.
      Weightlessness is unique to obtain more information on this complex interaction,
      because it is the only way to completely abolish the effects of gravity over
      longer periods. Results from space have been unexpected, because astronauts
      exhibit a fluid and sodium retaining state with activation of the sympathetic
      nervous system, which subjects during simulations by head-down bed rest do not.
      Therefore, the concept as to how weightlessness affects the cardiovascular system
      and modulates regulation of body fluids should be revised and new simulation
      models developed. Knowledge as to how gravity and weightlessness modulate
      integrated fluid volume control is of importance for understanding
      pathophysiology of heart failure, where gravity plays a strong role in fluid and
      sodium retention.

PMID- 16101472
TI  - The effect of gravitational acceleration on cardiac diastolic function: a
      biofluid mechanical perspective with initial results.
AB  - Echocardiographic measurements of astronaut cardiac function have documented an
      initial increase, followed by a progressive reduction in both left ventricular
      end-diastolic volume index and stroke volume with entry into microgravity (micro
      G). The investigators hypothesize that the observed reduction in cardiac filling
      may, in part, be due to the absence of a gravitational acceleration dependent,
      intraventricular hydrostatic pressure difference in micro-G that exists in the
      ventricle in normal gravity (1-G) due to its size and anatomic orientation. This
      acceleration-dependent pressure difference, DeltaP(LV), between the base and the
      apex of the heart for the upright posture can be estimated to be 6660 dynes/cm(2)
      ( approximately 5 mm Hg) on Earth. DeltaP(LV) promotes cardiac diastolic filling
      on Earth, but is absent in micro-G. If the proposed hypothesis is correct,
      cardiac pumping performance would be diminished in micro-G. To test this
      hypothesis, ventricular function experiments were conducted in the 1-G
      environment using an artificial ventricle pumping on a mock circulation system
      with the longitudinal axis anatomically oriented for the upright posture at 45
      degrees to the horizon. Additional measurements were made with the ventricle
      horizontally oriented to null DeltaP(LV)along the apex-base axis of the heart as
      would be the case for the supine posture, but resulting in a lesser hydrostatic
      pressure difference along the minor (anterior-posterior) axis. Comparative
      experiments were also conducted in the micro-G environment of orbital space
      flight on board the Space Shuttle. This paper reviews the use of an automated
      cardiovascular simulator flown on STS-85 and STS-95 as a Get Away Special payload
      to test this hypothesis. The simulator consisted of a pneumatically actuated,
      artificial ventricle connected to a closed-loop, fluid circuit with adjustable
      compliance and resistance elements to create physiologic pressure and flow
      conditions. Ventricular instrumentation included pressure transducers in the apex
      and base as well as immediately upstream of the inflow valve and downstream of
      the outflow valve, and a flow probe downstream of the outflow valve. By varying
      the circulating fluid volume, ventricular function could be determined for
      varying preload pressures at a regulated, mean afterload pressure of 95 mm Hg.
      This variation in preload condition permitted the construction of a ventricular
      function curve for the micro-G environment for comparison to the same curve for
      the 1-G environment. Data were collected from both missions at the upper end of
      the ventricular function curve. Experiment operation in the 1-G, supine
      orientation or in the micro-G environment eliminated the DeltaP(LV) observed in
      the 1-G, upright orientation. Consistent with the hypothesis, additional atrial
      pressure was required in micro-G to obtain stroke volumes and flow rates similar
      to those measured in 1-G for the upright posture. The necessary increase in
      atrial pressure was approximately 5 mm Hg in these experiments. In the same range
      of flow rates and stroke volumes, similar flows were observed in the 1-G supine
      posture for atrial pressures intermediate to the 1-G upright and micro-G values,
      also consistent with the hypothesis. Additional experiments on board the Space
      Shuttle are in preparation to gather data across the rest of the normal
      physiologic range of the ventricular function curve.

PMID- 16101473
TI  - The immune system in space, including Earth-based benefits of space-based
      research.
AB  - Exposure to space flight conditions has been shown to result in alterations in
      immune responses. Changes in immune responses of humans and experimental animals
      have been shown to be altered during and after space flight of humans and
      experimental animals or cell cultures of lymphoid cells. Exposure of subjects to
      ground-based models of space flight conditions, such as hindlimb unloading of
      rodents or chronic bed rest of humans, has also resulted in changes in the immune
      system. The relationship of these changes to compromised resistance to infection
      or tumors in space flight has not been fully established, but results from model
      systems suggest that alterations in the immune system that occur in space flight
      conditions may be related to decreases in resistance to infection. The
      establishment of such a relationship could lead to the development of
      countermeasures that could prevent or ameliorate any compromises in resistance to
      infection resulting from exposure to space flight conditions. An understanding of
      the mechanisms of space flight conditions effects on the immune response and
      development of countermeasures to prevent them could contribute to the
      development of treatments for compromised immunity on earth.

PMID- 16101474
TI  - Diseases of the kidney: molecular mechanisms and current therapy.

PMID- 16101475
TI  - New developments in the field of cystic kidney diseases.
AB  - For quite some time the field of polycystic kidney disease has led a life at the
      fringe of kidney research, but with the cloning of the PKD1 and many other genes
      this situation has dramatically changed. Polycystic kidney disease often is a
      syndromic disease affecting a variety of organs in addition to the kidney. Most
      of the proteins involved in polycystic kidney disease have been localized to the
      primary cilium, an extension at the apical membrane of renal tubular epithelial
      cells, which may serve chemo- and mechanosensory functions. It is speculated that
      primary cilia and their associated proteins play a role in determining the proper
      tubular geometry.

PMID- 16101476
TI  - Molecular basis of IgA nephropathy.
AB  - IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and
      remains an important cause of end-stage renal failure. However, the basic
      molecular mechanism(s) underlying abnormal IgA synthesis, selective mesangial
      deposition with ensuing mesangial cell proliferation and extracellular matrix
      expansion remains poorly understood. Notably, the severity of tubulointerstitial
      lesions better predicts the renal progression than the degree of glomerular
      lesions. The task of elucidating the molecular basis of IgAN is made especially
      challenging by the fact that both environmental and genetic components likely
      contribute to the development and progression of IgAN. This review will summarize
      the earlier works on the structure of the IgA molecule, mechanisms of mesangial
      IgA deposition and pathophysiologic effects of IgA on mesangial cells following
      mesangial deposition. Recently, a series of important advances in the area of
      communication between the glomerular mesangium and renal tubular cells have
      emerged. These novel findings regarding the molecular pathogenesis of IgAN will
      be helpful in designing future directions for therapy.

PMID- 16101477
TI  - Cellular and molecular pathways that lead to progression and regression of renal
      fibrogenesis.
AB  - Renal fibrosis is a common consequence and often a central feature of all the
      progressive renal diseases that lead to end-stage renal failure. In comparison to
      wound healing, during kidney fibrosis the length of the post-inflammatory phase
      often exceeds and continues unchecked resulting in scar formation. Infiltrating
      immune cells and a heterogeneous colony of interstitial cells derived from a
      variety of cellular origins such as resident mesenchymal cells, tubular
      epithelial cells, circulating fibrocytes, and bone marrow derived stem cells,
      communicate with each other and with inflamed and surviving parenchymal cells via
      a network of cytokines and adhesion molecules to populate the renal
      tubulointerstitial space during early fibrogenesis. Such fibroblasts subsequently
      secrete abundant extracellular matrix to achieve architectural remodeling in
      parallel with functional deterioration. Renal fibrosis is a dominant determinant
      of the clinical outcome of patients and yet for the most part, current therapies
      are ineffective or only marginally effective. This review highlights recent
      advances in our understanding of the cellular and molecular events leading to the
      progression of renal fibrosis.

PMID- 16101478
TI  - Bone and the kidney: a systems biology approach to the molecular mechanisms of
      renal osteodystrophy.
AB  - Despite its apparent static condition, the skeleton undergoes a permanent process
      of remodeling mediated by osteoblasts and osteoclasts. The activity of these
      cells is regulated by a plethora of factors, ranging from mechanical stress to
      the effects of hormones to the immune system. One well-studied regulatory system
      involves the maintenance of calcium homeostasis through a network whose main
      regulatory components include ionized calcium, phosphate, parathyroid hormone and
      active vitamin D. This system establishes the link between bone and kidney, as
      one of the kidney's endocrine functions is the activation of vitamin D, while
      electrolyte homeostasis is one of its excretory functions. Impaired renal
      function leads to disturbances in this regulatory system, resulting in the
      complex syndrome of renal osteodystrophy that affects the majority of patients
      with chronic renal failure. This review summarizes the current understanding of
      bone physiology on a molecular level, examines some of the pathological pathways
      related to renal disease, and concludes with an outlook on how the emerging field
      of systems biology may contribute to a more dynamic and quantitative
      understanding of the physiology and pathophysiology of renal bone disease.

PMID- 16101479
TI  - Genetic and genomic approaches to glomerulosclerosis.
AB  - Chronic kidney disease (CKD) is common, progressive and expensive to manage.
      Although modifiable risk factors can be treated and outcomes improved, CKD
      remains a chronic disease with excessive morbidity and mortality. The completion
      of the human genome sequence and the advent of methodologies to define gene
      function provide new opportunities to manage and treat patients with CKD and
      other chronic diseases. Despite the lack of clear correspondence between genotype
      and phenotype and an obvious Mendelian inheritance pattern, CKD susceptibility
      has a genetic basis. In this review, we focus on recent studies of familial focal
      segmental glomerulosclerosis and the discoveries that have resulted from both
      genetic and genomic approaches used to understand its pathogenesis. Key slit
      diaphragm proteins were discovered using linkage analyses of these rare causes of
      glomerulosclerosis and subsequent work has characterized slit diaphragm function
      in health and disease. Podocyte dysfunction is now recognized as a key
      contributor to the functional and histologic derangements that characterize
      glomerular dysfunction in many common causes of CKD. In aggregate, these studies
      provide a paradigm for approaches to better define mechanisms of CKD and to
      identify novel therapeutic targets.

PMID- 16101480
TI  - Molecular genetic approaches for studying the etiology of diabetic nephropathy.
AB  - A critical challenge faced by clinical nephrologists today is the escalating
      number of patients developing end stage renal disease, a major proportion of
      which is attributed to diabetic nephropathy (DN). The need for new measures to
      prevent and treat this disease cannot be overemphasized. To this end, modern
      genetic approaches provide powerful tools to investigate the etiology of DN.
      Human studies have already established the importance of genetic susceptibility
      for DN. Several major susceptibility loci have been identified using linkage
      studies. In addition, linkage studies in rodents have pinpointed promising
      chromosomal segments that influence renal traits. Besides augmenting our
      understanding of disease pathogenesis, these animal studies may facilitate the
      cloning of disease susceptibility genes in man through the identification of
      homologous regions that contribute to renal disease. In human diabetes, various
      genes have been evaluated for their risk contribution to DN. This widespread
      strategy has been propelled by our knowledge of the glucose-activated pathways
      underlying DN. Evidence has emerged that a true association does indeed exist for
      some candidate genes. Furthermore, the in vivo manipulation of gene expression
      has shown that these genes can modify features of DN in transgenic and knockout
      rodent models, thus corroborating the findings from human association studies.
      Still, the exact molecular mechanisms involving these genes remain to be fully
      elucidated. This formidable task may be accomplished by continuing to harness the
      synergy between human and experimental genetic approaches. In this respect, our
      review provides a first synthesis of the current literature to facilitate this
      challenging effort.

PMID- 16101481
TI  - Conditional gene targeting in the kidney.
AB  - Complete mapping of the genome in a number of organisms provides a challenge for
      experimental nephrologists to identify potential functions of a vast number of
      new genes in the kidney. Since knockout technologies have evolved in the early
      eighties the mouse has become a valuable model organism. Researchers can now
      artificially eliminate the expression of specific genes in a mammalian organism
      and examine the phenotype. New developments have emerged that allow investigators
      to knock out a gene specifically in the kidney. Several kidney-specific promoters
      provide valuable tools and bacterial artificial chromosome (BAC) based techniques
      like recombineering will enhance both number and accuracy of new mouse lines with
      spatially controlled gene expression. In addition to spatial control,
      tetracycline- or tamoxifen-inducible systems, provide the possibility of
      influencing the temporal expression pattern of a gene enabling researchers to
      dissect its functions in adult organisms. Knocking out a gene will continue to be
      the gold standard for defining the role of a specific gene whereas tissue
      specific gene knockdown using RNA interference represents an alternative approach
      for generating lower-priced and fast loss of function models. In addition to
      reverse genetic approaches, forward genetic techniques like random mutagenesis in
      mice continue to evolve and will enhance our understanding of disease mechanisms
      in the kidney.

PMID- 16101482
TI  - Novel non-rodent models of kidney disease.
AB  - Kidney disease in the 21(st) century affects increasing numbers of individuals.
      We continue to be challenged by our lack of understanding of the pathophysiology
      of acute and chronic renal disease including genetic diseases involving the
      kidney. Rodent knockout animals or inbred strains have greatly contributed to our
      understanding of many monogenetic and complex diseases. Non-rodent animal models
      of disease have become more attractive since genomic data has become available
      for a variety of organisms that offer distinct advantages over mice and rats for
      ease in conducting high-throughput chemical or mutagenesis screens. It is thus
      timely to examine the physiology and pathophysiology of the kidney or kidney
      equivalents in these organisms to evaluate their relevance as models for human
      disease. In addition to organisms whose small size and accessibility facilitate
      large scale screening approaches, larger animals at the other end of the spectrum
      offer unique physiological advantages in both size equivalency to humans as well
      as, in some cases, physiological and pathophysiological responses that closely
      mimic those of humans. Here we review a selected number of non-rodent
      experimental models of kidney diseases, focusing on recent advances in the use of
      the worm Caenorhabditis elegans, the fruitfly Drosophila melanogaster, the
      zebrafish Danio rerio, the little skate Leucoraja erinacea, the MGH miniature
      swine, merino cross sheep, and the cow Bos taurus to study kidney disease.

PMID- 16101484
TI  - Triplex-forming oligonucleotides as potential tools for modulation of gene
      expression.
AB  - Triplex-forming oligonucleotides (TFOs) bind in the major groove of duplex DNA at
      polypurine/ polypyrimidine stretches in a sequence-specific manner. The binding
      specificity of TFOs makes them potential candidates for use in directed genome
      modification. A number of studies have shown that TFOs can introduce permanent
      changes in a target sequence by stimulating a cell's inherent repair pathways.
      TFOs have also been demonstrated to inhibit gene expression providing a possible
      role for these compounds in cancer therapy. This review summarizes the dual roles
      of TFOs for use in delivering DNA reactive compounds to a specific site in the
      genome or for introducing permanent changes in the target sequence through the
      introduction of an altered helical structure. In addition to compiling the ways
      in which TFOs have been successfully utilized, this review will explore
      conflicting reports of TFO bioactivity focusing on the variables which affect the
      efficacy in vitro of TFO mediated genomic modification which in turn may
      represent the obstacles encountered using TFOs to modulate gene expression in
      vivo.

PMID- 16101485
TI  - Recognition of triple helical nucleic acids by aminoglycosides.
AB  - Aminoglycosides, traditional RNA binders, were found to be a new class of triple
      helical nucleic acid-stabilizing ligands. Neomycin, of all the aminoglycosides,
      has shown the most significant effects in stabilizing DNA, RNA, and hybrid triple
      helices. When compared with minor groove binders or intercalators, neomycin
      excels at triple helical stabilization in most cases. Molecular modeling studies
      suggest that neomycin reaches into the larger Watson-Hoogsteen groove. The charge
      and shape complementarity are the key factors in neomycin-triplex recognition. By
      conjugating neomycin with intercalators such as BQQ (a potent triple helix
      intercalating agent designed by Helene), we have progressed in developing more
      potent triple helix stabilizing ligands. The design of such dual or even triple
      recognition ligands opens a new paradigm for recognition of triple helix nucleic
      acids. The article herein presents studies of neomycin as the first molecule that
      can selectively stabilize nucleic acid triplex structures. These studies are
      supported by our recent discovery that neomycin prefers to bind to A-like
      conformations, of which triple helix structures are known to display some
      characteristics. These findings will contribute to the development of a new
      series of triplex-specific ligands, and may contribute to either antisense or
      antigene therapies.

PMID- 16101486
TI  - Competition dialysis: an assay to measure the structural selectivity of drug
      nucleic acid interactions.
AB  - Competition dialysis is a powerful new tool for the discovery of ligands that
      bind to nucleic acids with structural- or sequence-selectivity. The method is
      based on firm thermodynamic principles and is simple to implement. In the
      competition dialysis experiment, an array of nucleic acid structures and
      sequences is dialyzed against a common test ligand solution. After equilibration,
      the amount of ligand bound to each structure or sequence is determined
      spectrophotometrically. Since all structures and sequences are in equilibrium
      with the same free ligand concentration, the amount bound is directly
      proportional to the ligand binding affinity. Competition dialysis thus provides a
      direct and quantitative measure of selectivity, and unambiguously identifies
      which of the structures or sequences within the sample array that are preferred
      by a particular ligand. Following the introduction of the method, competition
      dialysis has been used worldwide to probe a variety of ligand-nucleic acid
      interactions. This contribution will focus on new analytical approaches for
      extracting information from the database that resulted from the first-generation
      competition dialysis assay, in which binding data was gathered for the
      interaction of 126 compounds with 13 different structures and sequences. Such
      global analyses allow identification of compounds with unique types of binding
      selectivity.

PMID- 16101487
TI  - Camptothecin: roles of the D and E rings in binding to the topoisomerase I-DNA
      covalent binary complex.
AB  - The alkaloid camptothecin is the prototypical DNA topoisomerase I poison. This
      core structure has formed the basis for two marketed antitumor agents and
      numerous clinical candidates, and has been the focus of many synthetic and
      medicinal chemistry studies. Recent reports have furthered our understanding of
      the roles played by the D and E rings of camptothecin in stabilization of the
      enzyme-DNA-camptothecin ternary complex. Important parameters for further study
      and optimization include the facility of E-ring lactone hydrolysis and the
      prospects for replacing the E ring with more stable structures, the role of the
      14-CH group in binary complex binding, and the effect of ternary complex dynamics
      on the expression of cytotoxicity by the camptothecins.

PMID- 16101488
TI  - Etoposide, topoisomerase II and cancer.
AB  - Etoposide is an important chemotherapeutic agent that is used to treat a wide
      spectrum of human cancers. It has been in clinical use for more than two decades
      and remains one of the most highly prescribed anticancer drugs in the world. The
      primary cytotoxic target for etoposide is topoisomerase II. This ubiquitous
      enzyme regulates DNA under- and overwinding, and removes knots and tangles from
      the genome by generating transient double-stranded breaks in the double helix.
      Etoposide kills cells by stabilizing a covalent enzyme-cleaved DNA complex (known
      as the cleavage complex) that is a transient intermediate in the catalytic cycle
      of topoisomerase II. The accumulation of cleavage complexes in treated cells
      leads to the generation of permanent DNA strand breaks, which trigger
      recombination/repair pathways, mutagenesis, and chromosomal translocations. If
      these breaks overwhelm the cell, they can initiate death pathways. Thus,
      etoposide converts topoisomerase II from an essential enzyme to a potent cellular
      toxin that fragments the genome. Although the topoisomerase II-DNA cleavage
      complex is an important target for cancer chemotherapy, there also is evidence
      that topoisomerase II-mediated DNA strand breaks induced by etoposide and other
      agents can trigger chromosomal translocations that lead to specific types of
      leukemia. Given the central role of topoisomerase II in both the cure and
      initiation of human cancers, it is imperative to further understand the mechanism
      by which the enzyme cleaves and rejoins the double helix and the process by which
      etoposide and other anticancer drugs alter topoisomerase II function.

PMID- 16101489
TI  - Programmable DNA binding oligomers for control of transcription.
AB  - Mapping and sequencing the genetic blueprint in human, mice, yeast and other
      model organisms has created challenges and opportunities for chemistry, biology
      and human medicine. An understanding of the function of each of the approximately
      25,000 genes in humans, and the biological circuitry that controls these genes
      will be driven in part by new technologies from the world of chemistry. Many
      cellular events that lead to cancer and the progression of human disease
      represent aberrant gene expression. Small molecules that can be programmed to
      mimic transcription factors and bind a large repertoire of DNA sequences in the
      human genome would be useful tools in biology and potentially in human medicine.
      Polyamides are synthetic oligomers programmed to read the DNA double helix. They
      are cell permeable, bind chromatin and have been shown to downregulate endogenous
      genes in cell culture.

PMID- 16101490
TI  - Dications that target the DNA minor groove: compound design and preparation, DNA
      interactions, cellular distribution and biological activity.
AB  - Fluorescence microscopy of trypanosomes from drug treated mice shows that
      biologically active heterocyclic diamidines that target the DNA minor groove bind
      rapidly and specifically to parasite kinetoplast DNA (k-DNA). The observation
      that the kinetoplast is destroyed, generally within 24 hours, after drug
      treatment is very important for understanding the biological mechanism, and
      suggests that the diamidines may be inhibiting some critical opening/closing step
      of circular k-DNA. Given the uncertainties in the biological mechanism, we have
      taken an empirical approach to generating a variety of synthetic compounds and
      DNA minor groove interactions for development of improved and new biological
      activities. Furamidine, DB75, is a diphenyl-diamidine that has the curvature to
      match the DNA minor groove as expected in the classical groove interaction model.
      Surprisingly, a linear diamidine with a nitrogen rich linker has significantly
      stronger binding than furamidine due to favorable linker and water-mediated DNA
      interactions. The water interaction is very dependant on compound structure since
      other linear compounds do not have similar interactions. Change of one phenyl of
      furamidine to a benzimidazole does not significantly enhance DNA binding but
      additional conversion of the furan to a thiophene (DB818) yields a compound with
      ten times stronger binding. Structural analysis shows that DB818 has a very
      favorable curvature for optimizing minor groove interactions. It is clear that
      there are many ways for compounds to bind to k-DNA and exert specific effects on
      kinetoplast replication and/or transcription that are required to obtain an
      active compound.

PMID- 16101491
TI  - Target practice: aiming at satellite repeats with DNA minor groove binders.
AB  - Much progress has been made in recent years in developing small molecules that
      target the minor groove of DNA. Striking advances have led to the design of
      synthetic molecules that recognize specific DNA sequences with affinities
      comparable to those of eukaryotic transcription factors. This makes it feasible
      to modulate or inhibit DNA/protein interactions in vivo, a major step towards the
      development of general strategies of anti-gene therapy. Examples from anti
      parasitic drugs also suggest that synthetic molecules can affect a variety of
      cellular functions crucial to cell viability by more generally targeting vast
      portions of genomes based on their biased base composition. This provides a
      rationale for developing approaches based on selective interactions with broad
      genomic targets such as satellite repeats that are associated with structural or
      architectural components of chromatin essential for cellular proliferation. Using
      examples drawn from the Drosophila melanogaster model system, we review here the
      use of synthetic polyamides or diamidines that bind the DNA minor groove and can
      be used as highly selective agents capable of interfering with specific
      protein/DNA interactions that occur in A+T-rich repeated sequences that
      constitute a significant portion of eukaryotic genomes. The satellite
      localization of cellular proteins that bind the minor groove of DNA via domains
      such as the AT hook motif is highly sensitive to these molecules. A major
      consequence of the competition between these proteins and their synthetic mimics
      is an alteration of the nuclear localization and function of proteins such as
      topoisomerase II, a major target of anti-cancer drugs.

PMID- 16101492
TI  - Interfacial inhibitors of protein-nucleic acid interactions.
AB  - This essay develops the paradigm of "Interfacial Inhibitors" (Pommier and
      Cherfils, TiPS, 2005, 28: 136) for inhibitory drugs beside orthosteric
      (competitive or non-competitive) and allosteric inhibitors. Interfacial
      inhibitors bind with high selectivity to a binding site involving two or more
      macromolecules within macromolecular complexes undergoing conformational changes.
      Interfacial binding traps (generally reversibly) a transition state of the
      complex, resulting in kinetic inactivation. The exemplary case of interfacial
      inhibitor of protein-DNA interface is camptothecin and its clinical derivatives.
      We will also provide examples generalizing the interfacial inhibitor concept to
      inhibitors of topoisomerase II (anthracyclines, ellipticines,
      epipodophyllotoxins), gyrase (quinolones, ciprofloxacin, norfloxacin), RNA
      polymerases (alpha-amanitin and actinomycin D), and ribosomes (antibiotics such
      as streptomycin, hygromycin B, tetracycline, kirromycin, fusidic acid,
      thiostrepton, and possibly cycloheximide). We discuss the implications of the
      interfacial inhibitor concept for drug discovery.

PMID- 16101493
TI  - Inhibitor of the glutamate vesicular transporter (VGLUT).
AB  - The vesicular glutamate transporter (VGLUT) is responsible for the uptake of the
      excitatory amino acid, L-glutamate, into synaptic vesicles. VGLUT activity is
      coupled to an electrochemical gradient driven by a vacuolar ATPase and stimulated
      by low Cl-. VGLUT has relatively low affinity (K(m) = 1-3 mM) for glutamate and
      is pharmacologically and structurally distinct from the Na+-dependent, excitatory
      amino acid transporters (EAATs) found on the plasma membrane. Because
      glutamatergic neurotransmission begins with vesicular release, compounds that
      block the uptake of glutamate into the vesicle may reduce excitotoxic events.
      Several classes of competitive VGLUT inhibitors have emerged including amino
      acids and amino acid analogs, fatty acids, azo dyes, quinolines and alkaloids.
      The potency with which these agents inhibit VGLUT varies from millimolar (amino
      acids) to nanomolar (azo dyes) concentrations. These inhibitors represent highly
      diverse structures and have collectively begun to reveal key pharmacophore
      elements that may elucidate the key interactions important to binding VGLUT.
      Using known inhibitor structures and preliminary molecular modeling, a VGLUT
      pharmacophore is presented that will aid in the design of new, highly potent and
      selective agents.

PMID- 16101494
TI  - Non-invasive molecular imaging of beta-adrenoceptors in vivo: perspectives for
      PET-radioligands.
AB  - Recently, the spectrum of molecular imaging devices such as positron emission
      tomography (PET) was further expanded by the now clinically available combined
      imaging modalities such as PET-CT and the preclinically used small animal PET
      scanners. These are powerful tools that can bridge the gap between preclinical
      and clinical evaluation studies of new radiotracers for molecular imaging of
      healthy and diseased states in vivo. The beta-adrenoceptor (beta-AR) radioligands
      discussed in this review represent a class of molecular probes for the non
      invasive in vivo assessment of beta-AR density eg. in the heart with PET. The
      beta-AR radioligands (S)-[11C]CGP 12177 (1) or (S)-[11C]CGP 12388 (2) are
      currently investigated in clinical studies with PET. Additionally, subtype
      selective beta1-AR radioligands are used in preclinical research which show
      potential for the diagnostics of the "beta1-AR organ" as such the heart can be
      defined. Non-invasive quantification of beta-ARs could facilitate the accurate
      choice and control of therapeutic interventions. Here we summarize the state-of
      the-art of the radiochemistry of radioactive beta-AR radioligands.

PMID- 16101495
TI  - Update of the preclinical situation of anticancer platinum complexes: novel
      design strategies and innovative analytical approaches.
AB  - Research in the field of bioinorganic chemistry has been stimulated by the
      worldwide success of the anticancer drug cisplatin. 40 years after the first
      report about its biological activity, carboplatin and oxaliplatin are in routine
      clinical use today, whereas nedaplatin, lobaplatin, and heptaplatin (SKI2053R)
      are only approved in Japan, China, and South Korea, respectively. Up to now,
      about 35 platinum complexes entered clinical trials in order to circumvent the
      side-effects and the problem of tumor resistance to cisplatin. Additionally,
      improvement of tumor selectivity as well as the need for a broader spectrum of
      indications are the motivations for tremendous efforts in the development of
      novel anticancer platinum-based drugs. New synthetic strategies and innovative
      analytical approaches provide a basis for a deeper understanding of the
      pharmacological profile of cisplatin and analogues (biodistribution, clearance,
      detoxification, side-effects, tumor specificity, cellular uptake, acquired or
      intrinsic resistance, platinum-DNA adduct removal by the cellular machinery) and
      give rise to a rational design of promising anticancer platinum coordination
      compounds. This article reviews the recent development of preclinical platinum
      complexes with interesting in vitro and in vivo tumor inhibiting properties. It
      focuses also on innovative synthetic strategies leading to novel classes of
      platinum complexes. A small part of the review is dedicated to new analytical
      approaches which have been supplied to or emerged in this field of research.

PMID- 16101496
TI  - Synthesis of novel test compounds for antiviral chemotherapy of severe acute
      respiratory syndrome (SARS).
AB  - This contribution reviews the synthesis of a range of experimental drugs designed
      for and aiming at antiviral chemotherapy of severe acute respiratory syndrome
      (SARS) coronavirus (SARS-CoV)-induced human disease conditions. The selection of
      25 test materials includes eleven trioxa-adamantane-triols (TATs) [BN, IBNCA,
      ABNCA, VANBA, ethylVANBA, euBN, euVANBA, ansaBN, Ehrlich BN, [6]prismaneBN,
      nitrodiBN], trivially termed bananins, one trioxa-adamantan-ol (TAO) THYMOBA, one
      bis-bananin pi-bananin (piBN), one triazaadamantane delta-bananin (deltaBN),
      seven potential nucleic acid-binding drugs (XBQC, INDO, PivINDO, AZTRION, AZADO,
      AZOCYS, AZOGALL), one potential antiviral interferon-inducer and distant
      nucleoside analog diazon, one potential HIV protein Vif antagonist AZODIAZON, one
      folic acid-diazon condensate DIAZONOFOL, and one special nucleoside analog
      (fructoinosine/fructovir). Four of the eleven bananins (BN, IBNCA, VANBA, euBN)
      were already demonstrated to constitute effective inhibitors of SARS-CoV
      NSP10/nsp13 RNA/DNA helicase/NTPase protein ATPase enzymatic function. Bananin
      (BN) was an effective inhibitor of both SARS-CoV RNA/DNA helicase nucleic acid
      unwinding function and SARS-CoV (Coronaviridae, Coronavirus) RNA-viral
      replication in cell culture. In summary, at least one selected compound of the
      synthesized test materials represents an interesting drug candidate for treatment
      of SARS-CoV-induced human disease (SARS). Viewed in aspects of organic chemistry
      [6]prismaneBN and nitrodiBN are the first true hexaprismane derivatives
      synthesized, and all reported compounds are entirely new.

PMID- 16101497
TI  - Copper as a biocidal tool.
AB  - Copper ions, either alone or in copper complexes, have been used to disinfect
      liquids, solids and human tissue for centuries. Today copper is used as a water
      purifier, algaecide, fungicide, nematocide, molluscicide as well as an anti
      bacterial and anti-fouling agent. Copper also displays potent anti-viral
      activity. This article reviews (i) the biocidal properties of copper; (ii) the
      possible mechanisms by which copper is toxic to microorganisms; and (iii) the
      systems by which many microorganisms resist high concentrations of heavy metals,
      with an emphasis on copper.

PMID- 16101498
TI  - Clinical relevance of postprandial lipaemia.
AB  - Several studies showed that after a fatty meal, plasma triglyceride (TG) levels
      are higher in patients with coronary heart disease. This abnormality may explain
      why some individuals develop atherosclerotic disease despite normal fasting lipid
      values. TG-rich lipoproteins are involved in atherosclerosis and thrombosis. TG,
      remnant-like particle (RLP) cholesterol (RLP-C) and RLP-TG increase after fat
      load and could contribute to atherothrombosis. Postprandial lipaemia is not a
      uniform abnormality. Its pathophysiology is not yet entirely clarified; possibly,
      the response to dietary fat is a polygenic phenomenon. However, a link with
      insulin resistance is likely; this link as well as that with obesity is
      discussed. A substantial part of life is spent in the postprandial state.
      Therefore, several investigators described fat load tests. However, it is still
      difficult to establish normal postprandial TG ranges since only small numbers of
      subjects were studied and there is as yet no standardised method. A more
      simplified fat load test should be established for 'routine' use. In this review,
      we consider the metabolic features, prevalence and management of postprandial
      lipaemia. Treatment may involve lifestyle measures as well as the use of lipid
      lowering (e.g. fibrates or statins), weight reducing and hypoglycaemic drugs.

PMID- 16101499
TI  - Structures and total syntheses of the plecomacrolides.
AB  - The plecomacrolides are a large family of natural products typically featured
      with a 16- or 18-membered macrolactone possessing two conjugated diene units and
      a hemiacetal side chain. The macrocycle skeleton is connected with the side chain
      through a three-carbon linker, forming a biologically important intramolecular
      hydrogen bonding network among the lactone/linker/hemiacetal structural motif.
      Many members of the plecomacrolides act as selective inhibitors of vacuolar H+
      ATPases (V-ATPases) and they are considered to have the potential for treatment
      of postmenopausal osteoporosis. Significant progress has been achieved in recent
      years in the area of plecomacrolide total synthesis. These include the total
      synthesis of bafilomycin A1 by Evans, Toshima, Hanessian, and Roush, of
      bafilomycin V1 by Marshall, of hygrolidin by Hashimoto and Yonemitsu, of
      concanamycin F by Paterson and Toshima, and of formamicin by Roush. The synthetic
      strategies and key transformations used in the total synthesis are discussed.

PMID- 16101500
TI  - Synthesis and pharmacological activities of amine-boranes.
AB  - A number of amine-boranes and related derivatives possess a wide range of
      biological activities including antineoplastic, antiviral, hypolipidemic, anti
      inflammatory activities, anti-osteoporotic and dopamine receptor antagonist
      activities. The compounds include borane complexes of alpha-amino acids,
      aromatic, aliphatic and heterocyclic amines, and nucleosides. The syntheses of
      amine-borane derivatives are generally carried out by first preparing a tertiary
      amine- or phosphine-cyano- or carboxyborane to serve as a borane donor for a
      subsequent Lewis acid exchange reaction. Borane adducts of simple aliphatic
      amines, heterocyclic amines and nucleic acids demonstrated potent cytotoxic
      activity in vitro and in vivo against murine and human tumor models. These boron
      containing compounds were shown to inhibit DNA synthesis; such inhibition was
      caused primarily by reducing de novo purine biosynthesis via inhibition of PRPP
      amidotransferase, IMP dehydrogenase and dihydrofolate reductase activities.
      Aliphatic, heterocyclic and nucleoside amine-boranes have also been shown to
      possess hypolipidemic activity in mice and rats. Many boron derivatives from
      different chemical classes demonstrated both cytotoxic and hypolipidemic
      activities. They decreased low-density lipoprotein (LDL) cholesterol while
      increasing high-density lipoprotein (HDL) cholesterol levels. The mode of action
      of these compounds in the 50-100 microM concentration range appeared to be by
      increasing lipid excretion from the body and by inhibiting rate-limiting enzyme
      activities for the de novo synthesis of lipids and cholesterol (e.g.,
      phosphatidylate phosphohydrolase, ATP-dependent citrate lyase, cytoplasmic acetyl
      coenzyme A [CoA] synthetase, HMG CoA reductase, and acetyl CoA carboxylase).
      Selected amine-boranes (e.g., trimethylamine-cyanoborane, N-methylmorpholine
      cyanoborane, and the base-boronated 2'-deoxynucleosides) have anti-inflammatory,
      analgesic, anti-arthritic and anti-osteoporotic activities.

PMID- 16101501
TI  - Differential scanning calorimetry in life science: thermodynamics, stability,
      molecular recognition and application in drug design.
AB  - All biological phenomena depend on molecular recognition, which is either
      intermolecular like in ligand binding to a macromolecule or intramolecular like
      in protein folding. As a result, understanding the relationship between the
      structure of proteins and the energetics of their stability and binding with
      others (bio)molecules is a very interesting point in biochemistry and
      biotechnology. It is essential to the engineering of stable proteins and to the
      structure-based design of pharmaceutical ligands. The parameter generally used to
      characterize the stability of a system (the folded and unfolded state of the
      protein for example) is the equilibrium constant (K) or the free energy
      (deltaG(o)), which is the sum of enthalpic (deltaH(o)) and entropic (deltaS(o))
      terms. These parameters are temperature dependent through the heat capacity
      change (deltaCp). The thermodynamic parameters deltaH(o) and deltaCp can be
      derived from spectroscopic experiments, using the van't Hoff method, or measured
      directly using calorimetry. Along with isothermal titration calorimetry (ITC),
      differential scanning calorimetry (DSC) is a powerful method, less described than
      ITC, for measuring directly the thermodynamic parameters which characterize
      biomolecules. In this article, we summarize the principal thermodynamics
      parameters, describe the DSC approach and review some systems to which it has
      been applied. DSC is much used for the study of the stability and the folding of
      biomolecules, but it can also be applied in order to understand biomolecular
      interactions and can thus be an interesting technique in the process of drug
      design.

PMID- 16101502
TI  - Taurine analogues; a new class of therapeutics: retrospect and prospects.
AB  - Taurine was discovered more than two hundred years ago from animal sources. It is
      distributed in both mammals and non-mammals and its content is high in several
      tissues. For more than a century-and-a-half, taurine was regarded just as an end
      product of sulfur metabolism. Recently, taurine has been rediscovered and its
      beneficial effects in processes like epilepsy, hypertension, congestive heart
      failure and diabetes have been well-documented. It was patented and found some
      clinical utility, but being an amino acid, therapeutic use confronts limitations
      like restricted permeability and more. This necessitates the development of pro
      drugs (analogues) mainly derivatives of taurine. A large number of taurine
      derivatives have been reported in the literature with partial to marked activity.
      Taurine derivatives like taltrimide, acamprosate and tauromustine, are already in
      the market as anti-convulsant, anti-alcoholic and anti-cancer agents. Many other
      analogues are effective in experimental models. The in depth analysis of these
      analogues and their biological actions can provide certain clues for further
      consideration. In the present review, attempts have been made to provide
      synopsis, synthesis and symbiosis of chemical and biological actions, which may
      provide future guidance and facilitate further research in this area. The
      successful journey of these analogues to clinical utility is a healthy and happy
      sign and an index of bright future, and we hope that this review will provide
      enough input to ignite the minds.

PMID- 16101504
TI  - Drug-associated mitochondrial toxicity and its detection.
AB  - Mitochondrial dysfunction is a fundamental mechanism in the pathogenesis of
      several significant toxicities in mammals, especially those associated with the
      liver, skeletal and cardiac muscle, and the central nervous system. These changes
      can also occur as part of the natural aging process and have been linked to
      cellular mechanisms in several human disease states including Parkinson's and
      Alzheimer's, as well as ischemic perfusion injury and the effects of
      hyperglycemia in diabetes mellitus. Our knowledge of the effects of xenobiotics
      on mitochondrial function has expanded to the point that chemical structure and
      properties can guide the pharmaceutical scientist in anticipating mitochondrial
      toxicity. Recognition that maintenance of the mitochondrial membrane potential is
      essential for normal mitochondrial function has resulted in the development of
      predictive cell-based or isolated mitochondrial assay systems for detecting these
      effects with new chemical entities. The homeostatic role of some uncoupling
      proteins, differences in mitochondrial sensitivity to toxicity, and the pivotal
      role of mitochondrial permeability transition (MPT) as the determinant of
      apoptotic cell death are factors that underlie the adverse effects of some drugs
      in mammalian systems. In order to preserve mitochondrial integrity in potential
      target organs during therapeutic regimens, a basic understanding of mitochondrial
      function and its monitoring in the drug development program are essential. Toward
      this end, this review focuses on two topics, (1) the specific effects of
      xenobiotics on mitochondrial structure and function and (2) a summarization of
      current methods for quantifying these changes in a preclinical toxicology
      laboratory.

PMID- 16101503
TI  - STAT1 as a new molecular target of anti-inflammatory treatment.
AB  - Cyclooxygenase (COX) is widely considered as the molecular target of non-steroid
      anti-inflammatory drugs (NSAIDs). However, due to the harmful side effect
      frequently observed following chronic use, the development of new anti
      inflammatory agents is the matter of many studies. Signal transducers and
      activators of transcription (STAT) are a family of nuclear proteins mediating the
      action of a number of cytokines. Among them, STAT1 plays a critical role in the
      signal transduction pathway of interferon-gamma (IFN-gamma) and growth hormone.
      STAT1 cascade is one major signalling pathway converting the IFN-gamma signal
      into gene expression, such as inducible nitric oxide synthase (iNOS), COX,
      vascular cell adhesion molecules (VCAM) and intercellular cell adhesion molecules
      (ICAM), critically involved in different pathologies correlated to the
      inflammatory process. This review focuses the attention on an alternative
      approach to the development of novel drugs based on inhibition of STAT1 pathway.
      In this context, a growing interest has been focused on natural compounds. We
      have recently reported a several data indicating that green tea extract (GTE),
      St. John's Wort extract and epigallocatechin-3-gallate (EGCG) exhibit a specific
      and strong anti-STAT1 activity which is independent of their acclaimed strong
      anti-oxidant activity. More recently, GTE has been shown to protect heart damage
      from ischaemia/reperfusion in rats, suggesting that the protective effect of
      green tea might be correlated to its anti-STAT1 activity. The present review is
      aimed at providing data that STAT1 may potentially be claimed as a new molecular
      target of an anti-inflammatory treatment and that among natural compounds there
      are a number of anti-STAT1 substances.

PMID- 16101505
TI  - Development and characterization of drug delivery systems for targeting mammalian
      cells and tissues: a review.
AB  - Recent advances in the development of diagnostics and therapeutics in the fields
      of recombinant biochemistry, solid phase peptide synthesis as well as in
      galenical research have resulted in highly specific and efficient components.
      Presently, millions of patients can profit from these new therapeutic modalities.
      The application of an effective anti-tumor dose of drugs can lead to marked
      toxicity in patients. Therefore, safe and efficient possibilities to transport
      these compounds to the target are of outmost importance. The importance of drug
      delivery is pivotal in the wide area of pharmacological research. However, until
      now, this issue is still to be solved. The main goal of every drug delivery
      system is the delivery of a precise amount of a drug at a pre-programmed rate to
      the desired location in order to achieve the necessary drug concentration in the
      targeted organ for effective treatment. The key problem still remains the
      achievement of curative doses in a pharmacologically active state in the desired
      target while avoiding side effects. Although respectable advances can be
      recognized in this field, the currently applied mechanisms for the transport of
      therapeutic molecules across biological membranes still remain far from being
      efficient. Helper molecules could improve delivery to desired target sites.
      Presently, a number of efforts are made and a huge spectrum of biochemical,
      biological, medical, pharmaceutical and physical possibilities are arising.
      However, the design and development of successful therapies based on this
      technology still remains a great challenge.

PMID- 16101506
TI  - Regulation of cys-based protein tyrosine phosphatases via reactive oxygen and
      nitrogen species in mast cells and basophils.
AB  - Activation of mast cells and basophils is accompanied by the production of
      reactive oxygen and nitrogen species that regulate diverse signaling pathways
      leading to the release of inflammatory mediators and production of a variety of
      cytokines. Although the functional pathways of reactive oxygen and nitrogen
      species in vivo are not completely understood, some novel metabolic pathways can
      be envisioned based on recent findings that protein tyrosine phosphatases can be
      regulated by reversible oxidation. In this review, we describe major sources and
      targets of reactive oxide and nitrogen species in mast cells and basophils.
      Direct and indirect regulations of class I and II Cys-based protein tyrosine
      phosphatases (LMW-PTP, PTEN, PTP-PEST, SHP-2, PTP1B, PTPalpha, PTPepsilon, DEP-1,
      TC45, SHP-1, HePTP and LAR) are discussed. The combined data highlight the role
      of redox-regulated protein tyrosine phosphatases as targets in the development of
      new ways of therapeutic intervention in allergies and inflammatory diseases.

PMID- 16101507
TI  - Recent advances in new structural classes of anti-tuberculosis agents.
AB  - Tuberculosis (TB) is one of the most devastating diseases primarily due to
      several decades of neglect, and presents a global health threat of escalating
      proportions. TB is the second leading infectious cause of mortality today behind
      only HIV/AIDS. The impetus for developing new structural classes of anti
      tuberculosis drugs comes from the emergence of multi-drug resistant (MDR) strains
      to commonly used drugs, substantially longer durations of therapy that are needed
      as a result of resistance, and the resurgence of disease in immuno-compromised
      patients. Recent years have witnessed emergence of many new structural classes of
      anti-TB agents, which have exhibited promising activities against drug-sensitive
      and drug-resistant strains of the causative organism Mycobacterium tuberculosis.
      These analogs ideally should decrease the overall duration of therapy with
      improved efficacy, and exhibit mechanisms of action different from those of
      existing drugs to counter the resistant strains of M. tuberculosis. This review
      provides a comprehensive literature compilation on advances in the new structural
      classes of anti-TB analogs reported during the past five years. Our discussion
      and observations are concentrated on chemotherapeutic potential of alphabetically
      listed twenty-seven new structural classes of anti-tuberculosis agents that
      include:- acetamides, 5-arylidene-2-thiohydantoins, benzoxazoles and
      benzothiazoles, benzoic acid hydrazones, benzoxazines, carbohydrates, chalcones,
      coumarins, deazapteridines, imidazoles, indoloquinazolinones,
      isothiosemicarbazones, mycobactins, 1,8-naphthyridines, phenazines, purines,
      pyridines, N-pyridinylsalicylamides, pyrimidines and thymidines, pyrroles,
      quinolines, quinoxalines, terpenes, thiadiazine thiones, thiolactomycines,
      toludines, and triazoles.

PMID- 16101508
TI  - Multivalent compounds for antigen-specific B cell tolerance and treatment of
      autoimmune diseases.
AB  - This review covers the design and development of B cell Toleragens, compounds
      developed for the treatment of antibody-mediated autoimmune diseases by antigen
      specific suppression of autoantibodies. Multivalent forms of B cell epitopes
      consisting of oligonucleotides, peptides, proteins and polysaccharides are under
      various stages of development for treating systemic lupus nephritis,
      antiphospholipid syndrome, and organ rejection associated with
      xenotransplantation. The design and structure of the multivalent ligands are
      presented along with relevant biological results. Hapten-polymer conjugates that
      were used to elucidate the principles of B cell suppression are included.
      Multivalent ligands for T cell receptors and high affinity IgE receptors, which
      provide insight into immunoglobulin aggregation and signaling, are also briefly
      discussed.

PMID- 16101509
TI  - Biochemical properties of peptides encrypted in bovine milk proteins.
AB  - Milk proteins are precursors of many different biologically active peptides.
      These peptides are inactive within the protein sequence, requiring enzymatic
      proteolysis for release of the bioactive fragment from the proteins precursor. It
      is evident that activated peptides originating from milk proteins should be taken
      into account as potential modulators of various regulatory processes in the body.
      Activated peptides are potential modulators of various regulatory processes in
      the living system: immuno-modulatory peptides stimulate the activities of cells
      of the immune system and several cytomodulatory peptides inhibit cancer cell
      growth, antimicrobial peptides kill sensitive microorganisms, angiotensin-I
      converting enzyme (ACE)-inhibitory peptides exert an hypotensive effect, opioid
      peptides are opioid receptor ligands which can modulate absorption processes in
      the intestinal tract, mineral binding peptides may function as carriers for
      different minerals, especially calcium, antithrombotic peptides inhibit
      fibrinogen binding to a specific receptor region on the platelet surface and
      inhibit aggregation of platelets. Moreover, many milk-derived peptides reveal
      multifunctional properties, i.e. specific peptide sequences having two or more
      different biological activities have been reported. Bioactive peptides can
      interact with target sites (e.g. receptors, enzymes) at the luminal side of the
      intestinal tract, or they could be absorbed and reach any potential site of
      action in the system to elicit physiological effects. Bioactive peptides
      encrypted in bovine milk proteins can be produced on an industrial-scale and are
      claimed to be health enhancing components for functional foods, nutraceuticals
      and pharmaceutical preparations that are used to reduce risk of disease or to
      enhance certain physiological functions.

PMID- 16101510
TI  - Dendritic cells as pharmacological targets for the generation of regulatory
      immunosuppressive effectors. New implications for allo-transplantation.
AB  - Dendritic cells (DCs) play a central role in the establishment of
      tolerance/immunity, because they activate naive T cells (TCs). Therefore, the
      pharmacological modulation of DCs has become a major field of interest in
      immunology. A large body of literature has arisen from the studies of DC biology
      during immunosuppressive drug treatment. Immunosuppressive drugs have improved
      the therapeutic management of allograft organ transplantation and autoimmune
      diseases, significantly. There is now strong evidence that, DCs might be the key
      for antigen specific tolerance induction. Recently, the existence of a population
      of DCs that migrate to the regional lymph node in the steady state has been
      identified. Such steady state immature migrating DCs are loaded with tissue
      antigens and deliver self-antigens towards secondary lymphatic organs and might
      educate TCs towards self-tolerance. Latest experimental data from rodent solid
      organ allo-transplantation supports the idea, that DCs might even become
      regulatory DCs towards foreign antigen specific tolerance induction. Apparently,
      regulatory donor DCs invade host secondary lymphatic organs where they might
      eventually educate host TCs towards foreign antigen specific tolerance.
      Seemingly, it depends on the DC maturation state whether pharmacologically
      modulated DCs induce antigen specific long-term tolerance in allo-transplantation
      solid organ transplantation. Several authors reported a positive self-limiting
      feedback loop between tolerogenic DCs and allo-specific regulatory TCs. Thus, the
      DC-TC network appears as an exceptionally good target for pharmacological
      manipulations. Here we review how immunosuppressive agents interfere with DC
      maturation, migration and homeostasis. We are developing a rational to select
      different drugs for the generation of regulatory DCs, for allo-transplantation
      clinical settings.

PMID- 16101511
TI  - Retrovirus silencing and vector design: relevance to normal and cancer stem
      cells?
AB  - An obstacle confronting gene therapy in stem cells is transcriptional silencing
      of the vector. Here, we discuss recent data indicating that oncoretrovirus and
      lentivirus vectors are silenced by multiple epigenetic pathways that result in
      DNA methylation and histone modifications. Both vector types can be variegated in
      stem cells and expression is often extinguished during differentiation. We
      propose a novel model of retrovirus silencing in which epigenetic pathways
      compete to recruit histone deacetylases, de novo methyltransferases, histone H1
      and MeCP2 to the provirus. These chromatin modifications may act in concert with
      heterochromatin at or near the integration site to establish silencing or
      variegation respectively. Retrovirus vector designs for stem cells should delete
      virus silencer elements, incorporate strong positive regulatory elements and
      insulators, and avoid non-mammalian reporter genes. In addition, cancer stem
      cells that continually repopulate a growing tumour may share silencing pathways
      with normal stem cells. Ultimately, optimized vector designs may prove to be
      valuable tools for gene therapy of both normal and cancer stem cells.

PMID- 16101512
TI  - Genetic manipulation of human embryonic stem cells: a system to study early human
      development and potential therapeutic applications.
AB  - The successful derivation of human embryonic stem cell (hESC) lines by Thomson
      and colleagues [Thomson et al., 1998] provided a new area of investigation in
      both regenerative medicine and early human development. Fundamental study of the
      molecular and cellular mechanisms responsible for normal lineage development will
      rely on reproducible protocols to direct the differentiation of hESCs into
      specific lineages of interest and genetically manipulate both hESCs and their
      derivatives. Identifying standards for maintenance of hESCs, methods for
      controlled differentiation and genetic manipulation of hESCs and their
      derivatives will provide a foundation to explore their potential therapeutic use
      in cell and gene therapy. In the present review, our goal is to outline the
      latest advances in the field with particular focus on how hESCs and their
      derivatives can be genetically altered, how this may be useful in better
      understanding the cellular and molecular events of lineage differentiation, and
      how deregulation of these cellular processes may lead to abnormal development and
      disease.

PMID- 16101514
TI  - Delivering RNA interference to the mammalian brain.
AB  - RNA interference (RNAi) is a new modality in gene therapy which can elicit down
      regulation of gene expression and has enormous potential in the treatment of
      neurological diseases. RNAi is a conserved system through which double stranded
      RNA (dsRNA) guides sequence specific mRNA degradation. The RNAi apparatus may be
      artificially triggered by delivery of naked siRNA molecules or by plasmid-based
      expression of dsRNA. Before these techniques can be used as effective treatments
      in the brain, efficient methods of in vivo delivery must be devised. This review
      first describes the mechanism of RNAi, and then critically examines both viral
      and non-viral methods for delivery of RNAi to the mammalian brain. There have
      been a number of important recent publications in this field and the progress
      towards effective in vivo delivery of RNAi to the central nervous system is
      discussed. Finally, potential problems that must be considered before applying
      this technology to the human brain are outlined.

PMID- 16101513
TI  - Altering the tropism of lentiviral vectors through pseudotyping.
AB  - The host range of retroviral vectors including lentiviral vectors can be expanded
      or altered by a process known as pseudotyping. Pseudotyped lentiviral vectors
      consist of vector particles bearing glycoproteins (GPs) derived from other
      enveloped viruses. Such particles possess the tropism of the virus from which the
      GP was derived. For example, to exploit the natural neural tropism of rabies
      virus, vectors designed to target the central nervous system have been
      pseudotyped using rabies virus-derived GPs. Among the first and still most widely
      used GPs for pseudotyping lentiviral vectors is the vesicular stomatitis virus GP
      (VSV-G), due to the very broad tropism and stability of the resulting
      pseudotypes. Pseudotypes involving VSV-G have become effectively the standard for
      evaluating the efficiency of other pseudotypes. This review samples a few of the
      more prominent examples from the ever-expanding list of published lentiviral
      pseudotypes, noting comparisons made with pseudotypes involving VSV-G in terms of
      titer, viral particle stability, toxicity, and host-cell specificity. Particular
      attention is paid to publications of successfully targeting a specific organ or
      cell types.

PMID- 16101515
TI  - Transcriptionally targeted adenovirus vectors.
AB  - Adenovirus vectors are the most highly efficient vehicles currently available for
      gene transfer to mammalian cells. Their ability to transduce both proliferating
      and non-dividing cells allows in vivo gene delivery, but the wide spectrum of
      cell types infected by adenovirus necessitates a requirement for targeting,
      particularly if the transduced gene is detrimental when expressed in
      inappropriate tissues. Over the past decade, numerous investigators have examined
      tissue- or tumor-specific enhancer-promoters as a means to transcriptionally
      target genes delivered by adenovirus vectors. We review here recent developments
      in adenovirus vectors including improvements in the vector backbone to maintain
      promoter specificity. In addition, we discuss the regulatory elements directing
      cell-specific expression of genes encoding telomerase, prostate-specific antigen,
      probasin, osteocalcin, tyrosinase, alpha-fetoprotein, surfactant B, and
      mammaglobin. Recent results using these regulatory sequences to target Ad vectors
      to cancer cells are highlighted.

PMID- 16101516
TI  - The use of oncolytic vaccinia viruses in the treatment of cancer: a new role for
      an old ally?
AB  - The use of genetically engineered, tumor-targeting viruses as oncolytic agents
      has recently emerged as a promising new area for the development of novel cancer
      therapies. The first viruses to enter the clinic, such as ONYX-015 (an oncolytic
      adenovirus), provided evidence both for the safety and for the anti-tumor
      potential of this approach. The results of these early trials have also allowed
      investigators to examine the limitations of these viruses and to develop
      potentially far more effective approaches. In this review the development of such
      next generation viruses, in particular the potential use of strains of vaccinia
      virus, will be discussed. Vaccinia has an enormous history of use in humans and
      possesses many of the features felt to be beneficial for the creation of a
      successful virotherapy agent. It causes no known disease in humans, yet is
      capable of infecting almost all cell types with a subsequent rapid and lytic
      infection, which subsequently induces a vigorous local CTL immune response at the
      site of infection. Vaccinia also displays natural tumor tropism, and several
      approaches have been used to further limit viral replication to tumor cells and
      to optimize the immune response induced at the site of the tumor. Finally, the
      large cloning capacity of vaccinia allows for the addition of multiple foreign
      genes into the viral genome. This has been exploited to increase the bystander
      effect of the virus by immune modulation or by expression of pro-drug converting
      enzymes as well as to incorporate safety controls and reporters for in vivo
      molecular imaging. Initial clinical trials with these viruses further highlights
      their potential as the next generation of oncolytic agents and as highly
      effective future cancer therapies.

PMID- 16101518
TI  - Neutrophils and eosinophils: clinical implications of their appearance, presence
      and disappearance in asthma and COPD.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are common chronic
      disorders. Traditionally, asthma has been associated with an eosinophilic
      inflammation and COPD with neutrophilic inflammation. In this review we will
      highlight the maturation, recruitment, activation, action and apoptosis of these
      cells. In addition we will focus on the evidence for their presence in disease
      and suggest potential new therapeutic interventions.

PMID- 16101519
TI  - Transepithelial migration, necrosis and apoptosis as silent and pro-inflammatory
      fates of airway granulocytes.
AB  - In inflammatory airway diseases, granulocytes such as eosinophils and neutrophils
      infiltrate the tissue where they are thought to exert pathogenic activities. To
      avoid a catastrophic accumulation of activated granulocytes, their recruitment
      must be balanced by efficient cell clearance mechanisms. In this regard, the
      focus has been on elimination through apoptosis and subsequent engulfment of
      apoptotic cells by phagocytes. However, novel data suggest that in the airways,
      powerful non-apoptotic mechanisms are also critically involved in cell clearance.
      One such mechanism is transepithelial migration into the airway lumen where the
      mucociliary escalator executes the final elimination. The physiological clearance
      of tissue granulocytes is normally silent, but can under certain situations shift
      to become a pro-inflammatory event. For example, apoptotic cells that escape
      phagocytosis, disintegrate in a pro-inflammatory process called secondary
      necrosis. In other situations, granulocytes are triggered to undergo an active
      and violent cytolytic death. This delicate balance in vivo, between silent and
      violent properties of granulocyte demise, complicates the design of pro-apoptotic
      pharmacological interventions. On the other hand, this insight may also open
      possibilities to new exciting treatment strategies. In this context, promoting
      transepithelial migration, prevention of secondary necrosis, and boosting the
      macrophage phagocytic system appear as exciting treatment avenues.

PMID- 16101520
TI  - Pharmacological regulation of human eosinophil apoptosis.
AB  - Eosinophilic inflammation of the airways is a key characteristic of asthma. The
      balance between eosinophil recruitment into the lung and their removal from the
      lungs determines the number of eosinophils in the airways. Apoptosis or
      programmed cell death is of importance in the removal of eosinophils from the
      lungs. In asthma, eosinophil apoptosis is delayed. Glucocorticoids enhance
      eosinophil apoptosis, whereas beta(2)-agonists may delay apoptosis in
      eosinophils. Detailed knowledge on the mechanisms that regulate this process
      gives an opportunity to develop specific asthma therapies targeting the
      eosinophil. This review aims to focus on the signalling leading to or preventing
      apoptosis in human eosinophils as well as reviews the current evidence on the
      regulation of eosinophil apoptosis and/or survival in allergic diseases.

PMID- 16101521
TI  - Regulation of neutrophil apoptosis and removal of apoptotic cells.
AB  - The accumulation of neutrophils during inflammation is essential for the
      destruction and removal of invading microorganisms. However, for resolution of
      inflammation to occur, neutrophils must also be removed from the inflammatory
      site since these cells are capable of releasing tissue toxic molecules.
      Neutrophil removal has been shown to occur via apoptosis and phagocyte clearance
      of apoptotic cells. Therefore, manipulation of these processes is likely to be a
      key therapeutic strategy in the management of inflammatory disease. In this
      review, we examine mediators of neutrophil survival and apoptosis and the
      signalling pathways that regulate the balance between life and death in these
      cells.

PMID- 16101522
TI  - Anti-inflammatory mechanisms of glucocorticoids targeting granulocytes.
AB  - Asthmatic inflammation involves the recruitment and activation of inflammatory
      cells, and changes in the structural cells of the lung and asthma are
      characterized by an increased expression of components of the inflammatory
      cascade including cytokines, chemokines, growth factors, enzymes, receptors and
      adhesion molecules. The increased expression of these proteins seen in asthma is
      generally the result of enhanced gene transcription, since many of the genes are
      not expressed in normal cells but are induced in a cell-specific manner during
      the inflammatory process. There is clear evidence that neutrophils, long thought
      of as being transcriptionally inert, can respond to stimuli to induce
      inflammatory genes. Glucocorticoids are very effective in controlling the
      inflammation seen in asthmatic airways. Beyond their recognized actions on
      eosinophil and neutrophil apoptosis, glucocorticoids have profound effects on the
      chemotaxis, activation and release of mediators from granulocytes (eosinophils,
      neutrophils and basophils). Few mechanistic studies are available in these cells,
      but it appears that in granulocytes, glucocorticoids target the same signaling
      pathways, such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP
      1), that are important in other cells. We summarize these known mechanisms at the
      end of this review.

PMID- 16101523
TI  - Production and degradation of oxygen metabolites during inflammatory states in
      the human lung.
AB  - Lung represents a tissue that encounters a high oxidant burden but is also
      endowed with efficient protection against oxygen and reactive oxygen species
      (ROS). The oxidant stress experienced by the lung is enhanced by exogenous
      oxidant producing toxins most importantly pollutants and cigarette smoke, as well
      as by increased oxidant production during lung inflammation. The major oxidant
      generating enzymes present in human lung include NADPH oxidase, myeloperoxidase,
      eosinophil peroxidase and nitric oxide synthases, all of which are induced during
      inflammatory states. The antioxidant machinery of human lung against ROS is more
      versatile than often assumed. In addition to metal binding proteins, mucus
      components and small molecular weight antioxidants and vitamins, lung tissue
      possesses a highly cell specific and compartmentalized defense system containing
      several antioxidant enzymes with variable locations, inducibilities and kinetics.
      Inflammatory states like asthma, chronic obstructive lung disease (COPD) and
      parenchymal lung disorders have been shown to lead to serious disturbances in the
      oxidant/antioxidant balance of the lung with consequent oxidant mediated cell
      injury. Novel synthetic antioxidant mimetics may have the potential to slow or
      terminate the progression of lung diseases associated with free radicals.

PMID- 16101524
TI  - Nitric oxide production and signaling in inflammation.
AB  - Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory
      responses. It possesses cytotoxic properties that are aimed against pathogenic
      microbes, but it can also have damaging effects on host tissues. NO reacts with
      soluble guanylate cyclase to form cyclic guanosine monophosphate (cGMP), which
      mediates many of the effects of NO. NO can also interact with molecular oxygen
      and superoxide anion to produce reactive nitrogen species that can modify various
      cellular functions. These indirect effects of NO have a significant role in
      inflammation, where NO is produced in high amounts by inducible nitric oxide
      synthase (iNOS) and reactive oxygen species are synthesized by activated
      inflammatory cells. The present review deals with NO production and signaling in
      inflammation, especially in relation to human neutrophils and eosinophils.

PMID- 16101525
TI  - Control of eosinophil toxicity in the lung.
AB  - The inappropriate accumulation of eosinophils and the subsequent release of their
      potent pro-inflammatory mediator arsenal are thought to be important contributors
      to the pathogenesis of asthma and other allergic diseases. It is also becoming
      apparent that eosinophils may play a role in the orchestration of immune
      responses in the asthmatic lung. There is therefore much interest in the
      development of strategies to limit or prevent eosinophil-induced toxicity. The
      mechanisms by which eosinophils accumulate in the peribronchial tissues of the
      lung are complex and include enhanced differentiation and release from the bone
      marrow, selective adhesion and transendothelial migration, directed movement in
      response to specific chemotactic mediators and finally prolonged survival as a
      consequence of delayed apoptosis. Thus it can be appreciated that there are many
      points at which the toxicity of eosinophils can be limited or even prevented.
      Important areas for potential advances in glucocorticoid (GC) development include
      efforts to dissociate their anti-inflammatory effects from unwanted side effects.
      Other areas include the development of humanized monoclonal antibodies against IL
      4, IL-13 and IL-5 together with the inhibition of adhesion pathways and/or
      chemokines responsible for eosinophil accumulation in the asthmatic lung. Several
      avenues of research are currently underway in an attempt to define mechanisms by
      which pro-inflammatory cells such as eosinophils can be safely removed from the
      asthmatic lung through apoptosis induction and their subsequent ingestion by
      phagocytes. This review will discuss both the potential and shortcomings of these
      diverse approaches to limit eosinophil toxicity in the asthmatic lung.

PMID- 16101527
TI  - Toxicity and roles of reactive oxygen species.
AB  - The history of studies in biology regarding reactive oxygen species (ROS) is
      approximately 40 years. During the initial 30 years, it appeared that these
      studies were mainly focused on the toxicity or microbicidal-related agents of
      ROS. However, recent studies have identified another action regarding oxidative
      signaling, other than toxicity of ROS. Basically, it is suggested that ROS are
      reactive, and degenerate to biomacromolecules such as DNA and proteins, leading
      to deterioration of cellular functions as an oxidative stress. On the other hand,
      recent studies have shown that ROS act as oxidative signaling in cells, resulting
      in various gene expressions. For example, NADPH oxidase, a major source of
      superoxide radicals (O(2)(-)), expresses in various tissues such as leukocytes
      and cardiovascular systems, and ROS derived from the enzyme play important roles
      in cell proliferation, differentiation, and cell death. In this review, we have
      focused on and described the basic properties, toxicity, and roles of ROS.

PMID- 16101528
TI  - Oxygen radicals in inflammation and allergy related to viral infections.
AB  - Oxygen radicals including superoxide anion (O(2)(-)) and nitric oxide (NO) are
      involved in a variety of inflammatory diseases induced by viral infection. In
      this review, we focus on the role of oxygen radicals in allergic inflammation
      such as bronchial asthma induced by viral infection--specifically, with
      respiratory syncytial virus (RSV). This infection in early childhood is a risk
      factor for development of wheezing, significant decreases in pulmonary function,
      and increases in airway reactivity. RSV infection also exacerbates recurrent
      wheezing attacks in patients with established asthma. Recently, we have
      demonstrated that RSV enhanced superoxide production by human eosinophils
      stimulated with a lipid mediator such as platelet-activating factor. This
      response depends on a beta2 integrin, alphaMbeta2, which is critical for
      eosinophil effector functions. Our results suggest that eosinophils and their
      products promote RSV-induced airway inflammation in asthma. Close delineation of
      the mechanism by which RSV enhances eosinophilic inflammation in asthma should
      yield clues to more effective therapy.

PMID- 16101529
TI  - Inflammatory cells and oxygen radicals.
AB  - At sites of inflammation, multiple inflammatory cells including eosinophils,
      neutrophils, and macrophages are capable of generating reactive oxygen species
      (ROS), which can contribute to development of various diseases. In case of
      allergic inflammation, for example, the lung cells obtained by bronchoalveolar
      lavage (BAL) following antigen challenge generates superoxide anion at nanomolar
      concentrations. Eosinophils obtained from BAL following a segmental allergen
      challenge generate more superoxide anion than eosinophils obtained from the
      peripheral circulation. Such ROS may contribute not only to tissue injury but
      also to inflammatory reactions. For example, hydrogen peroxide can stimulate both
      neutrophil and eosinophil adhesion as an autocrine or paracrine mediator via the
      upregulation of beta2 integrin. Furthermore, ROS may alter morphological or
      functional properties of endothelial cells, including permeability and adhesion
      molecule expression. Thus, ROS can promote adhesive interaction between
      inflammatory and endothelial cells, which could culminate in manifestations of
      inflammatory diseases such as bronchial asthma.

PMID- 16101530
TI  - Role of oxygen radicals on bronchial asthma.
AB  - Bronchial asthma is an inflammatory disorder characterized by recruitment and
      activation of various inflammatory cells including eosinophils and T cells in the
      airway mucosa. Oxygen radicals are produced by inflammatory cells in the airways
      and/or inhaled directly from environmental air. There is ample evidence that
      oxygen radical production is increased in asthma and is closely related to the
      pathogenesis and that exogenous oxidants such as cigarette smoke and ozone
      directly cause asthma exacerbation. The mechanism by which oxygen radicals cause
      asthma pathology is oxidation or nitration of proteins, lipids, or DNA to cause
      dysfunction of these molecules. In addition, physiological antioxidant system,
      which is equipped to protect host from detrimental oxidants, is impaired in
      asthma, possibly because of inflammation. Thus, the imbalance between oxidant and
      antioxidant that is called oxidant stress is critical in asthma pathogenesis.
      Elegant technique to measure oxygen radicals and the footprints of oxidant stress
      in patients with asthma have been developed and give an important clue to
      evaluate possible involvement of oxygen radicals in individual pathophysiology.
      Therapeutic interventions that reduce oxidant stress and enhance antioxidant
      defense may be useful in the treatment of asthma.

PMID- 16101531
TI  - Oxidative stress-related molecules as a therapeutic target for inflammatory and
      allergic diseases.
AB  - There is a growing body of evidence that oxidative stress mediated by reactive
      oxygen species plays an important role in the pathogenesis of various kinds of
      allergic and non-allergic inflammation. These data suggest that blocking reactive
      oxygen species should be useful for amelioration of allergic or non-allergic
      inflammation in the respiratory and intestinal tracts. In addition, the
      modulation of oxidative stress-related molecules, such as inducible nitric oxide
      synthase and redox-sensitive transcriptional factors, may be useful for the
      regulation of these inflammatory responses. In this review, we have summarized
      the recent advances in the prevention of allergic or non-allergic inflammation,
      especially the diesel exhaust particle-induced respiratory allergic response and
      dextran sulfate sodium-induced intestinal inflammation in rodents.

PMID- 16101533
TI  - Neutrophil-derived cytokines: potential therapeutic targets in inflammation.
AB  - Polymorphonuclear neutrophils (PMNs) are usually thought of as the leukocyte
      population involved in acute inflammatory responses, acting as a first line of
      defense against invading microorganisms. These terminally differentiated cells
      are generally not thought of as an important source of de novo synthesis of
      polypeptide mediators. Recent progress has shown, however, that PMNs are able to
      synthesize cytokines in response to a variety of inflammatory stimuli and during
      certain pathological conditions. The expression profiles of PMN-derived cytokines
      are similar with those of monocytes/macrophages, major professional phagocytes.
      Like monocytes, PMNs are able to secrete proinflammatory cytokines [e.g., tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-1beta], both CC and CXC
      chemokines [e.g., IL-8, interferon-inducible protein 10 (IP-10) and macrophage
      inflammatory protein (MIP)-1alpha], and angiogenic factors [e.g., vascular
      endothelial growth factor (VEGF)]. The secretion of cytokines by activated PMNs
      is regulated by immunoregulatory cytokines such as interferon (IFN)-gamma, IL-4,
      IL-10 and IL-13. In addition to acute inflammatory responses, PMNs and PMN
      derived cytokines appear to be involved in the pathogenesis of such chronic
      inflammatory disorders as rheumatoid arthritis, inflammatory bowel diseases and
      mycobacterial infections. Conceivably, these findings place PMNs at a pivotal
      position where they regulate and orchestrate not only acute inflammatory
      responses but also chronic inflammation and immune regulation. As such,
      inhibition of PMN-derived cytokines is viewed as a potentially useful strategy
      for therapeutic immunointervention.

PMID- 16101534
TI  - Macrophages in inflammation.
AB  - The inflammatory process is usually tightly regulated, involving both signals
      that initiate and maintain inflammation and signals that shut the process down.
      An imbalance between the two signals leaves inflammation unchecked, resulting in
      cellular and tissue damage. Macrophages are a major component of the mononuclear
      phagocyte system that consists of closely related cells of bone marrow origin,
      including blood monocytes, and tissue macrophages. From the blood, monocytes
      migrate into various tissues and transform macrophages. In inflammation,
      macrophages have three major function; antigen presentation, phagocytosis, and
      immunomodulation through production of various cytokines and growth factors.
      Macrophages play a critical role in the initiation, maintenance, and resolution
      of inflammation. They are activated and deactivated in the inflammatory process.
      Activation signals include cytokines (interferon gamma, granulocyte-monocyte
      colony stimulating factor, and tumor necrosis factor alpha), bacterial
      lipopolysaccharide, extracellular matrix proteins, and other chemical mediators.
      Inhibition of inflammation by removal or deactivation of mediators and
      inflammatory effector cells permits the host to repair damages tissues. Activated
      macrophages are deactivated by anti-inflammatory cytokines (interleukin 10 and
      transforming growth factor beta) and cytokine antagonists that are mainly
      produced by macrophages. Macrophages participate in the autoregulatory loop in
      the inflammatory process. Because macrophages produce a wide range of
      biologically active molecules participated in both beneficial and detrimental
      outcomes in inflammation, therapeutic interventions targeted macrophages and
      their products may open new avenues for controlling inflammatory diseases.

PMID- 16101535
TI  - Pathways of T cell activation and terminal differentiation in chronic
      inflammation.
AB  - Immune and inflammatory responses are governed by antigen-specific T cells, whose
      activation, differentiation and effector function are induced by signals
      delivered via the T cell antigen receptor (TCR) and by costimulatory and cytokine
      receptors. The molecular events leading to the activation of naive T cells have
      been extensively studied and are well characterized. Much less is known about the
      molecular and biochemical events regulating the activation of T cells in chronic
      inflammatory diseases such as rheumatoid arthritis (RA). This review examines the
      current state of knowledge of T cell activation in chronic inflammation, focusing
      on RA, and summarizes experimental data which indicate that the chronic
      inflammatory process may profoundly affect TCR and cytokine signal transduction
      pathways. We present evidence suggesting that in chronic inflammation, the
      antigen-driven TCR-mediated processes are attenuated, while cytokine-driven
      effector responses are sustained or even enhanced. The possible implications of
      this inbalance are discussed.

PMID- 16101536
TI  - Therapeutic targets of misguided T cells in systemic lupus erythematosus.
AB  - It is widely accepted that T cells with defective function play a central role in
      the pathogenesis of systemic lupus erythematosus (SLE). The detailed molecular
      mechanism underlying the aberrant function of SLE T cells is now being revealed.
      The TCR zeta chain, transcription factor, elf-1, inflammation signal transducer
      NF-kB, and PKC theta have been identified as the responsible molecules. In
      contrast to the defective signal transduction molecules, surface structures such
      as adhesion molecules, and co-stimulators have been reported to increase in their
      expression and function. Glucocorticoids and immunosuppressive agents have
      greatly improved the outcome of acute diseases and 5-year survival rate. However,
      it is suggested that long-term survival and quality of life appears to be
      unsatisfactory. Although the medical management of SLE is not sufficient to
      warrant long-term survival of young patients, recent progress in anti-cytokine
      biologics therapy against rheumatoid arthritis (RA) has facilitated searching for
      the molecular targets of SLE. In this report, we briefly review the molecular
      basis of SLE pathogenesis, and discuss possible therapeutic targets in this
      disease, focusing particularly on signal transduction and adhesion molecules in T
      cells.

PMID- 16101537
TI  - The role of CXCR2/CXCR2 ligands in acute lung injury.
AB  - The mortality of acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS) remain high despite advances in our knowledge and intensive care. This
      supports the contention that we need to further our understanding of the
      mediators that are involved in the pathogenesis of ARDS. The pathogenesis of ARDS
      proceeds as a continuum from exudation and inflammation to a fibroproliferative
      phase of diffuse alveolar damage. While a number of mediators are involved in the
      pathogenesis of ARDS, members of the CXC chemokine family have been determined to
      play a critical and pleiotropic role in promoting both recruitment of
      inflammatory cells, as well as in mediating aberrant vascular remodeling during
      both phases of ARDS. The importance of the biology of CXC chemokines in ALI/ARDS
      will be discussed in this review.

PMID- 16101538
TI  - Bronchial epithelial cells in allergic reactions.
AB  - Bronchial epithelial cells (BEC) are known to play an integral role in the airway
      defense mechanism via mucociliary system as well as mechanical barriers. Recent
      studies further indicate that BEC produce and release biologically active
      compounds including lipid mediators, growth factors, endothelin and a variety of
      cytokines/chemokines important in the pathogenesis of airway disorders. Cytokines
      and chemokines produced by BEC include IL-6, IL-8, G-CSF, GM-CSF, RANTES, eotaxin
      and TARC. Pro-inflammatory cytokines IL-1 and TNF-alpha, generally upregulate
      expression and release these cytokines/chemokines. BEC from patients with
      bronchial asthma showed increased levels of mRNA for these potent inflammatory
      peptides. BEC also interact with immune and inflammatory cells by direct adhesion
      as well as by humoral factors including cytokines. For example, eosinophil
      adhesion to BEC may be an important signal for the activation and degranulation
      of eosinophils. BEC is also believed to take part in the airway mucosal immunity
      via Toll-like receptors. Finally, BEC may play a crucial role in the processes of
      airway remodeling by cross-talk with mesenchymal cells. These findings strongly
      suggest that BEC are actively involved as regulators of allergic inflammatory
      responses, and become a target for therapeutic intervention.

PMID- 16101539
TI  - Chemokines and their receptors in chronic pulmonary disease.
AB  - The incidence of asthma has continued to rise worldwide with the number of severe
      asthmatic episodes dramatically increasing especially in children. Over the past
      several years researchers have realized that by controlling the influx of
      inflammatory cells that damage the airway and perpetuate the chronic responses,
      asthmatic disease can be attenuated. The modulation of the immune/inflammatory
      response has been primarily managed by use of inhaled and/or oral steroids.
      However, more specific therapy focused on inflammatory cell influx is desired to
      target the appropriate cell populations and alleviate specific aspects of disease
      without non-specific side effects. The chemokine family of cytokines control
      recruitment of leukocyte populations through specific receptors that are
      differentially expressed by certain cellular populations in various immune
      environments. Defining the type of receptors that are displayed by key cell
      populations involved in asthmatic responses has been the focus of many academic
      and pharmaceutic programs. This review will highlight the various areas that have
      been identified and those that appear to provide a future for therapeutic
      intervention.

PMID- 16101540
TI  - Endothelial cells in inflammation and angiogenesis.
AB  - Endothelial cells are involved in leukocyte extravasation underlying
      inflammation. A number of adhesion molecules play a role in leukocyte-endothelial
      interactions. New vessel formation, termed angiogenesis, is also crucial for
      leukocyte extravasation. The outcome of neovascularization is highly dependent on
      the balance or imbalance between angiogenic mediators and inhibitors. There have
      been several attempts to therapeutically interfere with the cellular and
      molecular mechanisms, such as leukocyte-endothelial cell adhesion and
      angiogenesis. Most studies have been performed using animal models of various
      types of inflammation, such as arthritis. In addition, a very limited number of
      human clinical trials gave promising results. In this review, authors summarize
      the most relevant information on adhesion molecules, as well as angiogenic and
      angiostatic agents. In addition, further perspectives of anti-adhesive and anti
      angiogenic therapy are also discussed. Specific targeting of pathological
      endothelial function including adhesion and angiogenesis, may be useful for the
      future management of various inflammatory diseases.

PMID- 16101541
TI  - Osteoblasts and osteoclasts in bone remodeling and inflammation.
AB  - Bone homeostasis is maintained by a balance between bone resorption by
      osteoclasts and bone formation by osteoblasts. Osteoblasts not only play a
      central role in bone formation by synthesizing multiple bone matrix proteins, but
      regulate osteoclast maturation by soluble factors and cognate interaction,
      resulting in bone resorption. Osteoclast maturation requires stimulation by RANKL
      expressed on osteoblasts, and the cognate interaction is mediated by firm
      adhesion via ICAM-1. During the processes, pro-inflammatory cytokines such as IL
      1 and TNF-alpha, cause an imbalance in bone metabolism, by favoring bone
      resorption via the induction of RANKL and ICAM-1 on osteoblasts. These
      inflammatory signals originate from the immune system, the largest source of cell
      derived regulatory signals, and such immunological signals to the bone are
      transmitted primarily via osteoblasts to induce osteoclast maturation, resulting
      in secondary osteoporosis. Actually, such phenomena mainly occur at the interface
      between proliferating synovium and bone tissue in rheumatoid arthritis (RA).
      Thus, therapeutic strategies for these conditions, an anti-TNF-alpha antibody and
      an IL-1 receptor antagonist, effective for treating RA disease activity, also
      reduce secondary osteoporosis and joint destruction. Based on an improved
      understanding of immune signals, investigation of the suppression of cell
      functions may lead to improved understanding and better treatment of diseases of
      bone metabolism and osteoporosis.

PMID- 16101542
TI  - Keratinocytes in inflammatory skin diseases.
AB  - Although in the past, keratinocytes were considered simply as passive targets of
      immunological attack from infiltrating T lymphocytes, a number of studies have
      definitively demonstrated that keratinocytes actively participate in the
      cutaneous immune responses. Upon activation, keratinocytes express a plethora of
      cytokines, chemokines and accessory molecules, which can transmit both positive
      and negative signals to cells of innate and adaptive immunity. Dysregulation and
      abnormal expression of inflammatory mediators or their receptors in keratinocytes
      are relevant to the pathogenesis of chronic inflammatory skin diseases such as
      psoriasis, atopic dermatitis and allergic contact dermatitis.

PMID- 16101543
TI  - Prostaglandins and cyclooxygenases in glial cells during brain inflammation.
AB  - Many brain disorders such as Parkinson's disease, Alzheimer's disease,
      amyotrophic lateral sclerosis (ALS), Huntington, stroke, head trauma, and
      infection, are associated with inflammation that is involved in
      neuropathologenesis and hyperalgesis. Microglia and astrocytes act as immune
      cells in the inflamed brain. Both cell types, but especially microglia, are
      thought to contribute to the onset of inflammation in many brain diseases by
      producing deleterious proinflammatory mediators. Prostaglandins (PGs), which are
      critical mediators of physiologic processes and inflammation, are largely
      produced by activated microglia and reactive astrocytes during brain
      inflammation. These compounds are converted from arachnoidic acid (AA) by two
      isoforms of the cyclooxygenase (COX) enzyme, namely COX-1 and COX-2. In
      particular, the action of COX-2 and PGs in CNS inflammation has gained much
      attention recently. PGs have been found to act neuroprotectively by elevating
      intracellular cAMP levels in neurons. These molecules also function as anti
      inflammatory molecules to reduce the production of nitric oxide and
      proinflammatory cytokines, and to increase the expression of anti-inflammatory
      cytokines. However, accumulating evidence also shows that COX inhibitors
      alleviate various types of brain damage via suppressing inflammatory reactions.
      Accordingly, the roles of two COX enzymes in mediating inflammation and anti
      inflammation have recently been debated. We provide here a review of recent
      findings indicating that the reciprocal interaction of glial cell activation, COX
      enzymes and PGs mediates neurodegeneration and neuroprotection during brain
      inflammation. In addition, the mechanism by which PGs mediate signaling is
      discussed.

PMID- 16101544
TI  - Mesangial cells and glomerular inflammation: from the pathogenesis to novel
      therapeutic approaches.
AB  - The mesangium occupies a central anatomical position in the glomerulus, and also
      plays an important regulatory role in immune-mediated glomerular diseases, with
      an active participation in the response to local inflammation. In general, the
      mesangial cell responses to the pathological stimuli are associated with the main
      events of glomerular injury: leukocyte infiltration, cell proliferation and
      fibrosis. Leukocyte migration and infiltration into the glomerulus is responsible
      for the initiation and amplification of glomerular injury, and is mediated by
      adhesion molecules and chemokines, which can be locally synthesized by mesangial
      cells. The increase in mesangial cell number is also due to proliferation of
      intrinsic mesangial cell population. Regulatory mechanisms of mesangial cell
      replication include a complex array of factors which control cell proliferation,
      survival and apoptosis. Mesangial matrix accumulation leading to
      glomerulosclerosis, is a consequence of an imbalance between matrix production
      and degradation, and is controlled by growth factors and pro-inflammatory
      cytokines. The initial phase of immune-mediated glomerular inflammation depends
      on the interaction of immune complexes with specific Fc receptors in infiltrating
      leukocytes and resident mesangial cells, the ability of immune complexes to
      activate complement system, and on local inflammatory processes. Activated
      mesangial cells then produce many inflammatory mediators leading to amplification
      of the injury. This review will focus on the biological functions of mesangial
      cells that contribute to glomerular injury, with special attention to immune
      mediated glomerulonephritis. Furthermore, new therapies based on the
      pathophysiology of the mesangial cell that are being developed in experimental
      models are also proposed.

PMID- 16101545
TI  - Resident kidney cells and their involvement in glomerulonephritis.
AB  - Each year, worldwide, there is an increasing number of patients with chronic
      kidney disease that progress to end-stage renal disease. Glomerulonephritis (GN)
      is the commonest single cause of end-stage renal failure in the world. GN can be
      a manifestation of primary renal injury or may be a secondary feature of a
      systemic disease process, for example Systemic Lupus Erythematosus (SLE) and Anti
      Neutrophilic Cytoplasmic Antibody (ANCA) associated vasculitis. Understanding of
      the immunopathogenesis of GN has advanced considerably over the last 25 years,
      particularly the immune system's role. The injurious role of infiltrating
      leukocytes and humoral mediators has been emphasised, however, the contribution
      of intrinsic renal cells has proved difficult to define. Most evidence for the
      pro-inflammatory capacity of intrinsic renal cells has been derived from in vitro
      studies. Although cytokine production by intrinsic renal cells has been
      demonstrated by immunohistochemistry and in situ hybridisation studies in renal
      tissue during the development of GN, the functional contribution of this cytokine
      production to renal injury was unknown. Little was known about direct and
      specific interactions between different glomerular cell types and infiltrating
      leukocytes in the pathogenesis of GN. The development of mice with genetic
      deficiencies of pro-inflammatory mediators and cytokines, and the technique of
      bone marrow transplantation into irradiated recipients to produce chimeric mice
      with restricted cytokine expression has allowed in vivo assessment of the
      functional contribution made by intrinsic renal cells. Studies have demonstrated
      the significant contribution of intrinsic renal cell derived cytokines (e.g. TNF)
      in mediating GN, whereas others (IL-1beta) have a relatively minor role.

PMID- 16101546
TI  - Matrix metalloproteinase knockout studies and the potential use of matrix
      metalloproteinase inhibitors in the rheumatic diseases.
AB  - The matrix metalloproteinases (MMPs) comprise a family of enzymes that
      collectively can degrade all components of the extracellular matrix (ECM). MMPs
      play an important role in many physiological processes such as embryonic
      development and growth, tissue remodelling and repair. Overexpression and
      activation of MMPs contributes to many pathologies, including arthritis,
      cardiovascular disease, tumour progression and lung disease. Targeted mutagenesis
      has allowed investigators to examine the contribution of MMPs to these
      physiological and pathologic processes. In this manuscript, we will present an up
      to date review of these studies. Rheumatoid arthritis (RA) and osteoarthritis
      (OA) are chronic diseases that result in cartilage degradation and loss of joint
      function. MMPs have been implicated in the collagen breakdown that contributes to
      joint destruction. Current available drugs to treat arthritis are predominantly
      directed towards the control of pain and/or the inflammation associated with
      joint synovitis but they do little to reduce joint destruction. Synthetic MMP
      inhibitors have been developed and in animal models of OA and/or RA, these agents
      have shown chondroprotective effects. However, results from clinical trials in RA
      have been equivocal, with some studies being terminated because of lack of
      efficacy or safety concerns. Increased understanding of the structure, regulation
      and function of individual MMPs may lead to more effective strategies. Approaches
      aimed at multiple steps of the pathogenesis of arthritis may be needed to break
      the chronic cycle of joint destruction. In the future, it will be important to
      have drugs that prevent the structural damage caused by bone and cartilage
      breakdown.

PMID- 16101547
TI  - Dehydroepiandrosterone, dehydroepiandrosterone sulfate and related steroids:
      their role in inflammatory, allergic and immunological disorders.
AB  - Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are
      metabolic intermediates in the production of potent androgens, estrogens and
      other less well-characterized steroids. DHEA(S) and closely related steroid
      hormones have a variety of immunological effects both in vitro and in vivo in
      experimental animals and humans. Many of these effects have been demonstrated in
      animal models where there is little circulating DHEA(S), and the demonstrated
      effects are generally seen at concentrations of DHEA(S) which are supra
      physiological in man. The physiological role of DHEA(S) in the immunological
      system is unknown. Furthermore, the molecular mechanism of action of DHEA(S) is
      unclear. In this review, I focus on studies of the immunological effects of
      DHEA(S) and closely related steroid metabolites and analogs, mainly derived from
      literature published in the last five years. My purpose is to describe the
      demonstrated effects and to highlight some of the remaining major research issues
      in this field. These issues include defining the molecular mechanism of DHEA(S)
      action; determining whether the effect of DHEA(S) is related to the steroid
      itself or to a metabolic product of DHEA; determining the relationship of
      physiological function to the pharmacological effects; and determining the
      molecular basis for species-specific differences in effects.

PMID- 16101548
TI  - Chemokines and brain functions.
AB  - Chemokines are small secreted proteins that chemoattract and activate immune and
      non-immune cells both in vivo and in vitro. Besides their well-established role
      in the immune system, several recent reports have suggested that chemokines and
      their receptors may also play a role in the central nervous system (CNS). The
      best-known central action is their ability to act as immuno-inflammatory
      mediators. Indeed, these proteins regulate the leukocyte infiltration in the
      brain during inflammatory and infectious diseases. However, recent studies
      clearly demonstrate that chemokines and their receptors are constitutively
      expressed by glial and neuronal cells in the CNS, where they are involved in
      intercellular communication. The goal of this review is to summarize recent
      information concerning the role of chemokines in brain functions. The first part
      will focus on the expression of chemokines and their receptors in the CNS with
      the main spotlight on the neuronal expression. In the second part, we will
      discuss the role of chemokines and their receptors in normal brain physiology.
      Because several chemokines are involved in neuroinflammatory and
      neurodegenerative disorders, the role of chemokines and their receptors in these
      diseases is reviewed further in this section. In conclusion, the implication of
      chemokines in cellular communication could allow: i) to identify a new pathway
      for neuron-neuron and/or glia-glia and/or neuron-glia communications that are
      relevant to both normal brain function and neuroinflammatory and
      neurodegenerative diseases; ii) to develop new therapeutic approaches for still
      untreatable diseases further.

PMID- 16101549
TI  - Pro and antiinflammatory properties of toxins from animal venoms.
AB  - Accidents evoked by venomous animals are common in tropical regions. In Brazil,
      envenomation evoked by snakes, spiders and scorpions are an important public
      health problem. Their venoms are composed of a great number of toxins, which are
      capable of acting on tissue and plasma components with consequent toxic and
      pharmacological effects. On the other hand, the diversity of venom composition
      makes them important source of toxins that can be employed as scientific tools.
      Here we describe the mechanisms of anti and pro-inflammatory properties of toxins
      of Bothrops and Crotalus genus snakes and Loxosceles and Phoneutria genus spider
      venoms. The emphasis was to summarise, both in vivo and in vitro, studies that
      focused on the action of phospholipases, metalloproteinases and sphingomyelinase
      D on vascular and cellular aspects of the process as well as the complex network
      of chemical mediators involved.

PMID- 16101551
TI  - Role of nitric oxide and calpain activation in neuronal death and survival.
AB  - Dysregulation of intracellular calcium homeostasis is a common hallmark of
      degenerating neurons, at some point in the cell death cascade. It is also a
      feature of many neurological disorders, including stroke, epilepsy, trauma and
      several neurodegenerative diseases, commonly associated with the phenomenon of
      excitotoxicity. Nitric oxide (NO) is a signaling gaseous molecule formed in the
      brain as a part of the normal intracellular calcium signalling, playing highly
      diversified roles in cellular physiology. For the past 20 years, numerous studies
      have demonstrated that NO can acts as a neurotoxin in several disorders of the
      nervous system. More recent evidence shows that NO can also act as a
      neuroprotective agent. Calcium-dependent proteases, like calpains, were also
      shown to be activated in several conditions of the nervous system that involve
      excitotoxic neurodegeneration, and have been receiving increasing attention as
      therapeutical targets in recent years. In this review, we bring together the
      recent literature concerning the involvement of NO and calpains in neuronal
      survival and death. The biological pathways involved with NO and calpains may be
      good drug targets to alter neurodegenerative diseases.

PMID- 16101552
TI  - What can adenosine neuromodulation do for neuroprotection?
AB  - The possibility of repairing brain lesions is a crucial issue. Knowing how
      regeneration occurs allows novel concepts in the process of protecting the
      nervous system, in other words to induce and to develop neuroprotection. Brain
      insults cause irreversible tissue damage by at least three mechanisms: First,
      through consequences of mechanical disruption of neurons or their projections;
      secondly, through biochemical or metabolic changes that are initiated by the
      insult; and finally, through inflammatory reactions or gliotic changes. The
      cellular elements and the chemical neuro-mediators involved in brain injury act
      via interconnections between the cellular elements and their secretions; the
      immune system and the nervous system are highly regulated in normal physiology,
      which benefits the organism. When these cells suffer insults in the central
      nervous system (CNS), the connections between the systems are altered; these
      systems act together to strangulate the tissue, depriving it of the local control
      over microcirculation and necessary oxygen, rendering membrane potentials useless
      to modulate neuronal function. Surgical interventions during the stages of brain
      injury continue to progress as do biochemical and bioelectric therapeutics during
      the chronic and rehabilitation stages. There is some hope, too, for effective
      neuropharmacological intervention. The fact that chemical mediators are already
      part of normal physiology, whether during development or adulthood, means that
      their activity can be modified by specific agonists and antagonists to restore
      homeostasis or to promote the safe pathways that can lead to regeneration. This
      is the orientation of much of current basic and clinical research. During the
      past decade considerable experimental and clinical data have been accumulated
      regarding cellular and biochemical events associated with brain repair.

PMID- 16101553
TI  - The putative neuroprotective role of neuropeptide Y in the central nervous
      system.
AB  - Neuropeptide Y (NPY) is one of the most abundant and widely distributed
      neuropeptides in the mammalian central nervous system (CNS). An overview of the
      distribution of the G-protein coupled NPY receptor family (Y(1), Y(2), Y(4), Y(5)
      receptors) in the brain is described. The coexistence of NPY with other
      neurotransmitters and its wide distribution in several brain areas predict the
      high importance of NPY as a neuromodulator. Thus, the effect of NPY on the
      release of several neurotransmitters such as glutamate, gamma-aminobutyric acid
      (GABA), norepinephrine (NE), dopamine, somastotatin (SOM), serotonin (5-HT),
      nitric oxide (NO), growth hormone (GH) and corticotropin releasing factor (CRF)
      is reviewed. A neuroprotective role for NPY under physiological conditions and
      during hyperactivity such as epileptic-seizures has been suggested. We have shown
      previously that NPY inhibits glutamate release evoked from hippocampal nerve
      terminals and has a neuroprotective effect in rat organotypic hippocampal
      cultures exposed to an excitotoxic insult. Moreover, changes in NPY levels have
      been observed in different pathological conditions such as brain ischemia and
      neurodegenerative diseases (Huntington's, Alzheimer's and Parkinson's diseases).
      Taken together, these studies suggest that NPY and NPY receptors may represent
      pharmacological targets in different pathophysiological conditions in the CNS.

PMID- 16101554
TI  - Inflammation and neurogenesis in temporal lobe epilepsy.
AB  - The aim of the present review is to discuss the evidence supporting the
      hypothesis that inflammation and neurogenesis play an important role in temporal
      lobe epilepsy (TLE) and to examine whether possible strategies that involve the
      pharmacological manipulation of inflammation/neurogenesis can lead to the
      development of novel approaches for the treatment of epilepsy. Since it is not
      yet clear whether the neuron-glia response obtained in this pathology is a
      secondary effect of an aggressive inflammation or if it is somehow related to the
      cause of the epileptic condition, with the present review we guide the readers
      through the complex and ambiguous crosstalk between neuroimmunology and epilepsy.

PMID- 16101555
TI  - Molecular targets and therapeutic strategies in Huntington's disease.
AB  - This article provides an overview of the molecular mechanisms associated with
      striatal neuronal degeneration in Huntington's disease (HD), the most studied of
      the diseases caused by polyglutamine expansion. We discuss the current status of
      research in cellular and animal models of HD, in which protein aggregation,
      excitotoxicity, mitochondrial dysfunction, transcription deregulation, trophic
      factor starvation and the disruption of axonal transport appear to be key
      features for selective striatal neurodegeneration. We further emphasize some of
      the most promising current strategies in HD treatment. We delineate the molecular
      and cellular rationale underlying the development of new pharmaceutical
      interventions that offer new hope of future treatment for HD patients worldwide.

PMID- 16101556
TI  - Alzheimer's disease-associated neurotoxic mechanisms and neuroprotective
      strategies.
AB  - The characteristic hallmarks of Alzheimer's disease (AD), the most common form of
      dementia in the elderly, include senile plaques, mainly composed of beta-amyloid
      (Abeta) peptide, neurofibrillary tangles and selective synaptic and neuronal loss
      in brain regions involved in learning and memory. Genetic studies, together with
      the demonstration of Abeta neurotoxicity, led to the development of the amyloid
      cascade hypothesis to explain the AD-associated neurodegenerative process.
      However, a modified version of this hypothesis has emerged, the Abeta cascade
      hypothesis, which takes into account the fact that soluble oligomeric forms and
      protofibrils of Abeta and its intraneuronal accumulation also play a key role in
      the pathogenesis of the disease. Recent evidence posit that synaptic dysfunction
      triggered by non fibrillar Abeta species is an early event involved in memory
      decline in AD. The current understanding of the molecular mechanisms responsible
      for impaired synaptic function and cognitive deficits is outlined in this review,
      focusing on oxidative stress and disturbed metal ion homeostasis, Ca(2+)
      dysregulation, mitochondria and endoplasmic reticulum dysfunction, cholesterol
      dyshomeostasis and impaired neurotransmission. The activation of apoptotic cell
      death as a mechanism of neuronal loss in AD, and the prominent role of
      neuroinflammation in this neurodegenerative disorder, are also reviewed herein.
      Furthermore, we will focus on the more relevant therapeutical strategies
      currently used, namely those involving antioxidants, drugs for neurotransmission
      improvement, hormonal replacement, gamma- and beta- secretase inhibitors, Abeta
      clearance agents (Abeta immunization, disruption of Abeta fibrils, modulation of
      the cholesterol-mediated Abeta transport), non-steroidal anti-inflammatory drugs
      (NSAIDs), microtubules stabilizing drugs and kinase inhibitors.

PMID- 16101557
TI  - Neurodegenerative pathways in Parkinson's disease: therapeutic strategies.
AB  - Parkinson's disease (PD), considered one of the major neurological disorders, is
      characterized by the loss of dopaminergic neurons in the pars compacta of the
      substantia nigra and by the presence of intraneuronal cytoplasmic inclusions
      called Lewy bodies. The causes for degeneration of PD neurons remain unclear,
      however, recent findings contributed to clarify this issue. This review will
      discuss the current understanding of the mechanisms underlying Parkinson's
      disease pathogenesis, focusing on the current and potential therapeutic
      strategies for human treatment.

PMID- 16101558
TI  - Old and new drug targets in diabetic retinopathy: from biochemical changes to
      inflammation and neurodegeneration.
AB  - Diabetic Retinopathy (DR) is a major complication of diabetes and is a leading
      cause of blindness in western countries. DR has been considered a microvascular
      disease, and the blood-retinal barrier breakdown is a hallmark of this disease.
      The available treatments are scarce and not very effective. Despite the attempts
      to control blood glucose levels and blood pressure, many diabetic patients are
      affected by DR, which progresses to more severe forms of disease, where laser
      photocoagulation therapy is needed. DR has a huge psychological impact in
      patients and tremendous economic and social costs. Taking this into account, the
      scientific community is committed to find a treatment to DR. Understanding the
      cellular and molecular mechanisms underlying the pathogenesis of DR will
      facilitate the development of strategies to prevent, or at least to delay the
      progression of the disease. The involvement of the polyol pathway, advanced
      glycation end products, protein kinase C and oxidative stress in the pathogenesis
      of DR is well-documented, and several clinical trials have been conducted to test
      the efficacy of various drugs. More recent findings also demonstrate that DR has
      characteristics of chronic inflammatory disease and neurodegenerative disease,
      which increases the opportunity of intervention at the pharmacological level.
      This review presents past and recent evidences demonstrating the involvement of
      different molecules and processes in DR, and how different approaches and
      pharmacological tools have been used to prevent retinal cell dysfunction.

PMID- 16101559
TI  - Organotypic hippocampal slice cultures for studies of brain damage,
      neuroprotection and neurorepair.
AB  - Slices of developing brain tissue can be grown for several weeks as so-called
      organotypic slice cultures. Here we summarize and review studies using
      hippocampal slice cultures to investigate mechanisms and treatment strategies for
      the neurodegenerative disorders like stroke (cerebral ischemia), Alzheimer's
      disease (AD) and epilepsia. Studies of non-excitotoxic neurotoxic compounds and
      the experimental use of slice cultures in studies of HIV neurotoxicity, traumatic
      brain injury (TBI) and neurogenesis are included. For cerebral ischemia,
      experimental models with oxygen-glucose deprivation (OGD) and exposure to
      glutamate receptor agonists (excitotoxins) are reviewed. For epilepsia, focus is
      on induction of seizures with effects on neuronal loss, axonal sprouting and
      neurogenesis. For Alzheimer's disease, the review centers on the use of beta
      amyloid (Abeta) in different models, while the section on repair is focused on
      neurogenesis and cell migration. The culturing techniques, set-up of models, and
      analytical tools, including markers for neurodegeneration, like the fluorescent
      dye propidium iodide (PI), are reviewed and discussed. Comparisons are made
      between hippocampal slice cultures and other in vitro models using dispersed cell
      cultures, experimental in vivo models, and in some instances, clinical trials.
      New techniques including slice culturing of hippocampal tissue from transgenic
      mice as well as more mature brain tissue, and slice cultures coupled to
      microelectrode arrays (MEAs), on-line biosensor monitoring, and time-lapse
      fluorescence microscopy are also presented.

PMID- 16101560
TI  - Liposomal and viral vectors for gene therapy of the central nervous system.
AB  - Due to the presence of the blood-brain barrier, the central nervous system (CNS)
      is not easily accessible to systemically delivered macromolecules with
      therapeutic activity such as growth factors, cytokines or enzymes. Therefore, the
      expression of exogenously administered genes in the brain has been proposed for a
      wide variety of inherited and acquired diseases of the CNS, for which classical
      pharmacotherapy is unavailable or not easily applicable. Gene therapy to the CNS
      has been the target of a great number of studies aiming at finding a viable
      therapeutic strategy for the treatment of neurological disorders. This approach
      has already been used as a promising tool for brain protection and repair from
      neuronal insults and degeneration in several animal models, and is currently
      being applied in clinical trials. The choice of an appropriate vector system for
      transferring the desired gene into the affected brain area is an important issue
      for developing a safe and efficient gene therapy approach for the CNS. In this
      review, we focus on the various types of vectors that have been used for gene
      delivery into the CNS. Particular emphasis is given to their mode of preparation,
      biological activity, safety and in vivo behavior. Examples illustrating the
      potential of both viral and non-viral vectors in therapeutic applications to
      brain disorders are provided. In addition, the use of lentiviral vectors for in
      vivo modeling of genetic disorders of the CNS is discussed.

PMID- 16101561
TI  - Endothelial progenitor cells as potential drug targets.
AB  - Endothelial progenitor cells (EPC) are bone marrow derived cells with the
      potential to differentiate into mature functional endothelial cells. First
      clinical trials have been performed investigating the effects of EPC
      transplantation into cardiac ischemic areas after myocardial infarction, in
      patients with peripheral atherovascular disease or on endothelialisation of
      artificial heart valves. Next to EPC transplantation, the pharmacological
      mobilisation and functional modification of EPC may also play a major role in
      future therapies. Studies have raised the concern that patients with coronary
      heart disease or severe heart failure may suffer from decreased amounts and
      impaired function of peripheral circulating EPC. Drug induced mobilization of EPC
      and normalization of EPC function may therefore improve prognosis of certain
      cardiovascular diseases. The underlying molecular events of a disturbed
      mobilisation, differentiation, homing and/or function of EPC are not well
      understood. In the present review we will highlight the current knowledge of the
      role of EPC dysfunction in various cardiovascular diseases and focus on potential
      causally related molecular mechanisms, which might be novel drug targets.

PMID- 16101562
TI  - Endothelin receptor antagonists: another potential alternative for cardiovascular
      diseases.
AB  - Endothelin-1 (ET-1), the predominant isoform of the endothelin peptide family,
      has potent vasoconstrictor, mitogenic, pro-inflammatory and antinatriuretic
      properties which have been implicated in the pathophysiology of a number of
      cardiovascular diseases. ET-1 effects are mediated through activation of the G
      protein-coupled ETA and ETB receptors, which are found in a variety of cells
      including endothelial, vascular smooth muscle and mesangial cells. Overexpression
      of ET-1 has been consistently described in salt-sensitive models of hypertension
      and in models of renal failure, and has been associated with disease progression.
      The development of a range of peptidic and nonpeptidic ET-1 receptor antagonists
      represents an exciting breakthrough in cardiovascular therapeutics. Endothelin
      antagonists improve endothelium-dependent relaxation and ameliorate vascular and
      cardiac hypertrophy as well as glomerulosclerosis; interestingly, these
      beneficial effects seem to occur independently of their capacity to lower blood
      pressure. The comparison between selective ETA and combined ETA/ETB antagonists
      in experimental models of cardiovascular diseases reveals no differences in terms
      of their effects on blood pressure, LV hemodynamics or remodeling. In the case of
      salt-sensitive hypertension, ETA receptor blockade leads to the prevention of
      vascular hypertrophy and renal function improvement, being likely that these
      effects are also mediated by ETB receptors based on the fact that the concomitant
      blockade of ETB receptors prevents the beneficial effects of ETA antagonists. As
      a whole, the available data indicate that the use of ET-1 receptor antagonists
      might be of therapeutic interest to prevent hypertension induced end-organ
      damage; however, the comparative efficacy of selective ETA vs. dual ETA/ETB
      blockade to prevent target organ injuries in humans still remains to be
      investigated.

PMID- 16101563
TI  - Monocyte cyclooxygenase-2 activity: a new therapeutic target for atherosclerosis?
AB  - It is now widely accepted that atherosclerosis is a complex chronic inflammatory
      disorder of the arterial tree associated with several risk factors. From the
      initial phases of leukocyte recruitment to eventual rupture of vulnerable
      atherosclerotic plaques, a low-grade inflammation, also termed microinflammation,
      appears to play a key pathogenetic role. Experimental and clinical evidence
      suggests that cyclooxygenase-2 (COX-2), an enzyme which catalyzes the generation
      of prostaglandins from arachidonic acid, also contributes to lesion formation.
      COX-2 has been detected in macrophages, smooth muscle cells and endothelial cells
      in human atherosclerotic lesions. Several studies have also reported the presence
      of COX-2 in the shoulder region of atherosclerotic plaques, mainly colocalizing
      with macrophages and MMPs, enzymes that are involved in the destabilization of
      atherosclerotic plaques, leading to rupture and atherothrombotic syndromes (i.e.
      acute myocardial infarction). We have recently assessed monocyte COX-2 activity
      and the production of PGE(2) in a population of apparently healthy subjects free
      from clinically overt atherosclerosis. We found an association between increased
      PGE(2) and increasing number of cardiovascular risk factors and carotid intima
      media thickness, a noninvasive surrogate marker of atherosclerosis, independently
      of traditional and non traditional cardiovascular risk factors. Our findings
      support the notion that the COX-2/PGE(2)axis may have a role in atherosclerosis,
      and this might be an attractive therapeutic target. COX-2 inhibitors,
      collectively called coxibs (celecoxib, rofecoxib, valdecoxib, lumiracoxib, etc),
      held a promise of improved treatment of arthritis without the gastrointestinal
      side effects associated with aspirin and other nonsteroidal anti-inflammatory
      drugs. However, clinical studies raise several clinically relevant questions as
      to their beneficial role in atherosclerosis prevention, because of increased
      thrombogenicity and cardiovascular risk. Only well designed large scale clinical
      trials can provide the answer as to the net effect of selective COX-2 inhibition
      on cardiovascular events before this new class of anti-inflammatory drugs can be
      incorporated into the armamentarium of atherosclerosis.

PMID- 16101564
TI  - Drug eluting stents in interventional cardiology -- current evidence and emerging
      uses.
AB  - Intervention in coronary artery disease is an area of cardiology where novel
      drugs, in the form of drug-eluting stents (DES), are being used increasingly
      commonly. DES are used across the whole range of coronary intervention, from
      stable angina patients with single or multivessel disease, acute coronary
      syndromes and acute myocardial infarction (i.e. primary angioplasty). Most
      recently, they are being tested in a particularly challenging subset of patients,
      those experiencing symptoms due to restenosis within a previously stented area of
      vessel (in-stent restenosis, ISR). This article summarises the rationale for the
      use of DES, across all these areas, focussing specifically on the emerging
      results of trials and registries examining the effectiveness of DES in acute
      myocardial infarction (AMI) and ISR. Drug-eluting stents represent a significant
      shift in the use of locally-delivered drugs in interventional cardiology. On the
      basis of encouraging trial data, including in the specific areas of in-stent
      restenosis and myocardial infarction, their use is becoming extremely widespread
      in place of bare-metal (drug-free) stents. This change is happening despite their
      high costs, relatively short follow-up data and concerns of possible unwanted
      effects, because of the weight of evidence that they are superior in preventing
      restenosis in many patient groups. This reduction is highly significant in
      angiographic terms and, to a lesser degree, in the prevention of clinically
      important restenosis requiring revascularisation, but not clearly in terms of
      overall mortality.

PMID- 16101565
TI  - The Na(+)/H(+) exchanger: a target for cardiac therapeutic intervention.
AB  - The Na(+)/H(+) exchanger (NHE) is a ubiquitous protein present in mammalian
      cells. In higher eukaryotes this integral membrane protein removes one
      intracellular H(+) for one extracellular Na(+) protecting cells from
      intracellular acidification. NHE is of essential importance in the myocardium. It
      prevents intracellular acidosis that inhibits contractility. NHE also plays a key
      role in damage to the mammalian myocardium that occurs during ischemia and
      reperfusion and is involved in hypertrophy of the myocardium. NHE is composed of
      a membrane bound domain of approximately 500 amino acids plus a hydrophilic
      regulatory cytoplasmic domain of approximately 315 amino acids. The NHE1 isoform
      is the only significant plasma membrane isoform present in the myocardium. The
      activity of NHE1 is elevated in animal models of myocardial infarcts and in left
      ventricular hypertrophy. During ischemia and reperfusion of the myocardium, NHE
      activity catalyzes increased uptake of intracellular sodium. This in turn is
      exchanged for extracellular calcium by the Na(+)/Ca(2+) exchanger resulting in
      calcium overload and damage to the myocardium. Numerous inhibitors of NHE have
      been developed to attempt to break this cycle of calcium overload. In animal
      models excellent success has been obtained in this regard. However in humans,
      clinical trials have resulted in only modest success and recently, significant
      detrimental side effects were note of one NHE inhibitor. The mechanisms by which
      these inhibitors affect NHE activity are presently being investigated and regions
      of the protein important in NHE activity and inhibitor efficacy are related but
      not identical. Future studies may develop superior inhibitors that may circumvent
      recently reported side effects. Recently, NHE inhibition has been shown to be
      remarkably effective in preventing hypertrophy in some animal models. Whether
      this proves to be a practical treatment for hypertrophy in humans has yet to be
      determined.

PMID- 16101566
TI  - Reviewing the cardiovascular complications of HIV infection after the
      introduction of highly active antiretroviral therapy.
AB  - Studies published before the introduction of highly active antiretroviral therapy
      (HAART) have tracked the incidence and course of human immunodeficiency virus
      (HIV) infection in relation to cardiac disease.The introduction of HAART
      regimens, by preventing opportunistic infections and reducing the incidence of
      myocarditis, has reduced the prevalence of HIV-associated cardiomyopathy of about
      30% and the prevalence of cardiac involvement of AIDS-associated malignancies of
      about 50%. However, HAART regimens, especially those including protease
      inhibitors have been shown to cause, in a high proportion of HIV-infected
      patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2
      diabetes mellitus, insulin resistance) that may be associated with an increased
      risk of cardiovascular disease (approximately 1.4 cardiac events per 1000 years
      of therapy according to the Framingham score). A careful stratification of the
      cardiovascular risk and cardiovascular monitoring of patients under HAART
      according to the most recent clinical guidelines is needed.

PMID- 16101567
TI  - Imaging of visceral adipose tissue: an emerging diagnostic tool and therapeutic
      target.
AB  - Several lines of evidence support the contention that excess visceral fat plays a
      significant role in the development of an unfavourable metabolic and
      cardiovascular risk profile. Hence, estimation of visceral adipose tissue (VAT),
      that is, the fat surrounding the internal organs, might be important for
      cardiovascular risk stratification. Classically, anthropometric measures have
      been employed to assess body fat distribution for risk assessment. But more
      recently, imaging methods for visceral fat quantitation have become a focus of
      attention particularly in a clinical research setting. Several imaging methods
      have evolved for estimation of VAT mass. Among these, magnetic resonance imaging
      (MRI) is fairly well established, but ultrasound and magnetic resonance
      spectroscopy (MRS) are also emerging as useful methods for quantitation of VAT
      and fat tissue content in vivo. Ultrasound is the most cost-effective and a
      convenient imaging tool whereas MRS is still in its infancy but it is highly
      promising because of its high sensitivity and specificity. There is a compelling
      need to quantify VAT not only for diagnostic purposes, but also for therapeutic
      interventions with weight reduction drugs or pharmaceuticals targeted to with
      adipose tissue. For example, changes in regional fat distribution can be used to
      estimate drugs effectiveness and their mechanism of action. Therefore, in this
      review I shall present briefly latest and main imaging techniques to detect the
      visceral adiposity, including the new ultrasound measurements of different
      visceral adipose tissue compartments. Some visceral adipose tissues which are not
      traditionally assessed, such as intraperitoneal, mediastinal and the relatively
      small depots, such as epicardial adipose tissue have also been recently studied
      and are now proposed as new markers of visceral adiposity.

PMID- 16101569
TI  - Xenobiotic nuclear receptor-mediated regulation of UDP-glucuronosyl-transferases.
AB  - UDP-glucuronosyltransferases (UGTs) belong to the Phase II drug metabolizing
      enzymes. UGTs mediate the transfer of glucuronic acid, from UDP glucuronic acid
      to predominantly hydrophobic xeno- and endobiotic chemicals, thus facilitating
      their detoxification and excretion. Deficiency in the expression and/or activity
      of UGTs may lead to genetic and acquired diseases such as Crigler-Najjar syndrome
      and jaundice. UGT genes are classified into UGT1A and UGT2B subfamily, and each
      subfamily and each isoform shows tissue-specific distribution pattern. The
      underlying mechanisms for this tissue specificity are not fully understood.
      Emerging evidence have demonstrated that nuclear receptors (NR), such as pregnane
      X receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator
      activated receptor (PPAR), can regulate UGTs and this NR-mediated regulation may
      contribute to the tissue-specific expression pattern of UGTs. The regulations are
      believed to be both receptor- and UGT isoform-specific. In addition, UGTs are
      also subject to the regulation by aryl hydrocarbon receptor (AhR) and other
      tissue-specific transcription factors. Based on their capacity to catalyze the
      glucuronidation of xenobiotics and endobiotics, UGTs play an important role in
      hormonal homeostasis, energy metabolism, bilirubin clearance, and xenobiotic
      detoxification. Therefore, elucidating UGT regulation by nuclear receptors has
      broader significance in understanding UGT's function in various physiological and
      patho-physiological conditions.

PMID- 16101570
TI  - Regulation of sulfotransferases by xenobiotic receptors.
AB  - The transcription factor networks that regulate basal and xenobiotic-modulated
      expression of the hepatic sulfotransferases affect the dynamics of xenobiotic
      detoxication, carcinogen bioactivation and metabolic homeostasis. Emerging
      evidence suggests that liver-enriched transcription factors, the aryl hydrocarbon
      (Ah) receptor and members of the nuclear receptor transcription factor
      superfamily all play integrated roles in the control of sulfotransferase gene
      transcription. Unlike the well known up-regulation of CYP1A1, expression of rat
      hepatic aryl (SULT1A1) and hydroxysteroid (SULT2A) sulfotransferase is suppressed
      in response to treatment with the prototypic Ah receptor ligand, 2, 3, 7, 8
      tetrachlorodibenzo-p-dioxin. Glucocorticoid-inducible rat hepatic SULT1A1 gene
      transcription occurs through a glucocorticoid receptor (GR)-mediated mechanism,
      while human hepatic SULT1A1 does not display GR-inducible expression. By
      comparison, liver-enriched transcription factors, such as CCAAT/enhancer binding
      protein, are essential for the maintenance of basal and GR-inducible rat hepatic
      SULT2A expression. The transcriptional control of rodent and human hepatic SULT2A
      expression is subject to trans-activation by the environmental sensor, pregnane X
      receptor (PXR). IR0 (inverted repeat with zero intervening bases) motifs located
      in the 5'-flanking regions of rodent SULT2A genes are required for
      transcriptional activation by PXR and other nuclear receptors, including
      constitutive androstane receptor, farnesoid X receptor and vitamin D receptor.
      Peroxisome proliferator activated receptor alpha (PPARalpha) mediates the
      induction of human, but not rat, hepatic SULT2A gene transcription, thus
      implicating a role for fatty acids as endogenous regulators of hepatic
      sulfonation in humans. This review focuses on the xenobiotic sensors and
      transcription factor systems that regulate sulfotransferase gene expression.

PMID- 16101571
TI  - Regulation of hepatic transporters by xenobiotic receptors.
AB  - Chemicals that increase expression of phase-I and -II biotransformation enzymes
      in liver, as well as enhance hepatic uptake and biliary excretion are often
      referred to as microsomal enzyme inducers (MEIs). Early studies suggested that
      drug metabolism might be coordinately regulated along with drug efflux from
      hepatocytes as a means for the liver to rid itself of foreign chemicals. Since
      then, the identification and characterization of nuclear receptors (NRs) has
      aided in understanding of how various MEIs enhance xeniobiotic uptake,
      biotransformation, and excretion. In addition, the NRs by which several classes
      of MEIs induce phase-I and -II drug metabolizing enzymes have been elucidated
      (i.e. AHR, CAR, PXR, PPARalpha, Nrf2). Several transporter families which mediate
      uptake of chemicals into liver and excretion of chemicals from liver into blood
      and/or bile have been cloned and identified. In general, the organic anion
      transporting polypeptide family (Oatps) along with Organic cation transporter 1
      (Oct1) and Organic anion transporter 2 mediate uptake of a large number of
      xenobiotics from blood into liver. Conversely, Multidrug resistance proteins
      (Mdrs), Multidrug resistance-associated proteins (Mrps), and Breast cancer
      resistance protein (Bcrp) mediate efflux of xenobiotics from liver into bile or
      blood. Recent studies have demonstrated that MEIs increase expression of various
      Oatps, Mrps, and Mdrs in liver, and some occur via activation of nuclear
      receptors.

PMID- 16101572
TI  - CAR, the continuously advancing receptor, in drug metabolism and disease.
AB  - The detoxification and elimination of potentially toxic foreign and endogenous
      compounds depends on the concerted action of xenobiotic metabolizing enzymes.
      Nuclear hormone receptors (NHRs) have emerged as key regulators of the expression
      of these enzymes and his review focuses on the xenosenor CAR (Constitutive
      Androstane Receptor, NR1I3). CAR is highly expressed in the liver and the small
      intestine, two key tissues expressing xenobiotic metabolizing enzymes, and
      mediates the induction of their expression by the widely used antiepileptic drug,
      phenobarbital (PB) and the potent synthetic inducer 1, 4-bis-(2-(3, 5, 
      dichloropyridyloxy)) benzene (TCPOBOP). TCPOBOP is an agonist ligand for CAR. PB
      induces its nuclear translocation, which results in increased expression of CAR
      target genes since, unlike the classical, ligand-dependent nuclear receptors, CAR
      is an apparently constitutive transactivator. This constitutive activity is
      inhibited by the inverse agonist ligands androstanol and androstenol. The CAR
      mediated induction of the expression of xenobiotic metabolizing enzymes is
      generally protective, but can be deleterious if toxic metabolites are produced.
      CAR also has a protective role in the stress response elicited by
      hyperbilirubinemia, as well as lithocholic acid induced cholestasis. In addition,
      recent studies show that CAR activation disrupts thyroid hormone homeostasis.
      Finally, CAR activation promotes hepatocyte proliferation and blocks apoptosis,
      and is essential for the tumorigenesis induced by its activators PB and TCPOBOP.
      The role of CAR in endobiotic and xenobiotics metabolism has clinical
      implications in disease prevention, drug-drug interactions, and the development
      of better drug treatments.

PMID- 16101573
TI  - Animal models of xenobiotic receptors.
AB  - Retinoid X receptors (RXRs) form heterodimers with pregnane X receptor (PXR) and
      constitutive androstane receptor (CAR), two prototypical xenobiotic receptors,
      and mediate metabolism of xenobiotics (foreign compounds) and endobiotics
      (endogenous compounds). Establishment of gene knockout and transgenic mouse
      models of RXRs, PXR, and CAR greatly enhanced the study of the biology of nuclear
      receptors, leading to considerable research progress in understanding the
      molecular mechanism underlying the nuclear receptor-mediated pathways in
      xenobiotic and endobiotic metabolism. These animal models are widely used in
      screening nuclear receptor ligands, identifying nuclear receptor target genes,
      and defining physiological and pharmacological pathways mediated by these
      xenobiotic nuclear receptors. In addition, "humanized" PXR and CAR mouse models,
      which avoid species specificity, provide valuable tools for investigating human
      xenobiotic response. Moreover, generations of multiple gene knockout mouse models
      further allow us to identify unique and redundant pathways mediated by each
      xenosensor. In this article, we review the progress made by using animal models
      of RXRs, PXR, and CAR in understanding the biological functions of these nuclear
      receptors in physiology, pharmacology, and pathology.

PMID- 16101574
TI  - Structure and function of the human nuclear xenobiotic receptor PXR.
AB  - The pregnane X receptor (PXR) is a member of the nuclear receptor family of
      ligand-regulated transcription factors. Like many former orphan nuclear
      receptors, it contains both DNA and ligand binding domains and binds to response
      elements in the regulatory regions of target genes as a heterodimer with
      RXRalpha. Unlike the vast majority of nuclear receptors, however, PXR responds to
      a wide variety of chemically distinct xenobiotics and endobiotics, regulating the
      expression of genes central to both drug and bile acid metabolism. We review the
      structural basis of PXR's promiscuity in ligand binding, its recruitment of
      transcriptional coregulators, its potential formation of higher-order nuclear
      receptor complexes, and its control of target gene expression. Structural
      flexibility appears to be central to the receptor's ability to conform to ligands
      that differ both in size and shape. We also discuss the clinical implications of
      PXR's role in the drug-drug interactions, cancer, and cholestatic liver disease.

PMID- 16101575
TI  - Genetic variants of PXR (NR1I2) and CAR (NR1I3) and their implications in drug
      metabolism and pharmacogenetics.
AB  - The defense mechanisms responsible for protecting the body from endogenous toxins
      are also involved in the metabolism of drugs and are composed of phase I and
      phase II drug metabolizing enzymes, as well as drug transporters. Numerous drugs
      and chemicals have been shown to modulate the expression of the genes involved in
      these three drug-detoxifying processes. Induction of these genes contributes to
      both auto-induction of drug clearance and to drug-drug interactions in
      combination therapies. The orphan nuclear receptors PXR (pregnane X receptor) and
      CAR (Constitutive androstane receptor) are xenosensors that mediate drug-induced
      changes by increasing transcription of genes that are involved in drug clearance
      and disposition. Co-administration of drugs, one of which is a nuclear receptor
      agonist or antagonist, can either lead to altered clearance of the second drug
      and severe toxicity, or a loss of therapeutic efficacy or an imbalance in
      physiological substrate concentrations, providing a novel molecular mechanism for
      drug-drug interactions. Thus, genetic variability in these nuclear receptors will
      contribute to human variation in the magnitude of clinically significant drug
      drug interactions. This review describes common PXR and CAR genetic variants that
      have been identified to date in the human population and the functional
      consequence of these variant alleles. In addition, alternatively spliced variants
      of PXR and CAR that may also contribute to individual variability as well as
      tissue specific expression of these receptors are also described. Identification
      of PXR and CAR genetic variants and alternatively spliced mRNAs may ultimately
      allow predictions of interindividual differences in target gene induction and
      drug-drug interactions.

PMID- 16101576
TI  - Beyond CAR and PXR.
AB  - It is becoming increasingly evident that constitutive, induced, and regulated
      expression of genes important to the drug disposition process such as drug
      transporters, phase I and II metabolic enzymes are largely under the
      transcriptional control of certain nuclear receptor (NR) family members. In the
      past decade, important new insights regarding the role and relevance of ligand
      activated nuclear receptors such as such as the pregnane X receptor (PXR) and
      constitutive androstane receptor (CAR) in terms of their activation by endogenous
      biochemicals, natural products, as well as synthetic compounds have led to a much
      better understanding of the xenobiotic-mediated induction process and the
      clinical relevance of such NRs to drug therapy in general. However, in addition
      to CAR and PXR, many orphan and adopted orphan NRs have recently been identified
      as key regulators of drug disposition genes. Indeed, nuclear receptors including
      farnesoid X receptor, peroxisome proliferator-activated receptor, and hepatocyte
      nuclear factors (1alpha, 3 and 4alpha) exhibit overlapping ligand specificities
      and regulate multiple gene targets, resulting in tissue- and organ-specific
      expression of drug disposition genes. In this review, the biology,
      pathophysiology, and the potential clinical relevance of such NRs to drug
      disposition and response are discussed.

PMID- 16101578
TI  - Combinatorial synthesis of anti-HIV agents--a review.
AB  - Combinatorial chemistry has been well recognized as an important tool of drug
      discovery. An ongoing hand is to integrate the combinatorial approach with
      fundamentals of medicinal chemistry and rational drug design. The last five years
      has seen an explosion in the exploration and adoption of combinatorial
      techniques. Indeed, it is difficult to identify any other topic in chemistry that
      has ever caught the imagination of chemists with such fervor and with the
      continuous development of high throughput screening methods. There is a growing
      need for the synthesis of a large number of molecules. Compound libraries
      designed to produce specific inhibitors of therapeutic target proteins have
      generated significant interest in drug discovery research. Combinatorial
      chemistry provides the opportunity to generate large libraries of compounds for
      biological testing. A literature search revealed that many lead compounds have
      indeed been discovered from libraries and this review presents a survey of
      combinatorial synthesis of HIV-1 reverse transcriptase inhibitors, protease
      inhibitors, HIV-1 function inhibitors such as adsorption inhibitors, CCR5
      antagonists and HIV-1 Tat-tar inhibitors that can be developed as potential anti
      HIV drugs.

PMID- 16101579
TI  - Combinatorial chemistry as a tool for targeting different stages of the
      replicative HIV-1 cycle.
AB  - In the present era, acquired immunodeficiency syndrome (AIDS) is the most fatal
      disorder for which no completely successful chemotherapy has been developed so
      far. The pandemic spread of this disease has prompted an unprecedented scientific
      and clinical effort to understand and combat it. A number of targets has been
      identified to stop the replication of the virus at different stages of its life
      cycle: Reverse Transcriptase (RT), protease (PR) and CCR5 are the most promising
      targets. Although highly active antiretroviral therapy (HAART) has been effective
      in reducing the mortality and morbidity in recent years, adverse side effects of
      the chemotherapy, patient non-compliance and the development of viral resistance
      remain major problems. With the aim to find better drug candidates with minor
      adverse side effects in recent years, several groups have investigated
      combinatorial approaches for the generation of libraries of HIV PR inhibitors
      while only few contributions to the preparation of libraries of HIV Reverse
      Transcriptase (RT) and CCR5 inhibitors are available. This review summarizes the
      recent developments of combinatorial chemistry in this area.

PMID- 16101580
TI  - "In silico" design of potential anti-HIV actives using fragment descriptors.
AB  - Substructural Molecular Fragments (SMF) method was applied for computer-aided
      design of new compounds potentially possessing high anti-HIV activities:
      tetrahydroimidazobenzodiazepinone (TIBO) derivatives and 1-[2
      hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives. Using available
      experimental data, the SMF method was first applied to build QSAR models based on
      fragment descriptors (atom/bond sequences and "augmented atoms"). The focused
      virtual combinatorial libraries containing 891 TIBO derivatives and 2640 HEPT
      derivatives were then generated systematically attaching selected substituents to
      corresponding Markush structures. Finally, a screening of those libraries using
      developed QSAR models led to several hits potentially possessing high anti-HIV
      activity.

PMID- 16101581
TI  - Virtual screening for anti-HIV-1 RT and anti-HIV-1 PR inhibitors from the Thai
      medicinal plants database: a combined docking with neural networks approach.
AB  - The virtual screening approach for docking small molecules into a known protein
      structure is a powerful tool for drug design. In this work, a combined docking
      and neural network approach, using a self-organizing map, has been developed and
      applied to screen anti-HIV-1 inhibitors for two targets, HIV-1 RT and HIV-1 PR,
      from active compounds available in the Thai Medicinal Plants Database. Based on
      nevirapine and calanolide A as reference structures in the HIV-1 RT binding site
      and XK-263 in the HIV-1 PR binding site, 2,684 compounds in the database were
      docked into the target enzymes. Self-organizing maps were then generated with
      respect to three types of pharmacophoric groups. The map of the reference
      structures were then superimposed on the feature maps of all screened compounds.
      Only the structures having similar features to the reference compounds were
      accepted. By using the SOMs, the number of candidates for HIV-1 RT was reduced to
      six and nine compounds consistent with nevirapine and calanolide A, respectively,
      as references. For the HIV-1 PR target, there are 135 screened compounds showed
      good agreement with the XK-263 feature map. These screened compounds will be
      further tested for their HIV-1 inhibitory affinities. The obtained results
      indicate that this combined method is clearly helpful to perform the successive
      screening and to reduce the analyzing step from AutoDock and scoring procedure.

PMID- 16101582
TI  - Topological descriptors in modeling the HIV inhibitory activity of 2-aryl-3
      pyridyl-thiazolidin-4-ones.
AB  - The HIV-1 RT inhibitory activity of 2-(2,6-dihalophenyl)-3-(substituted pyridin-2
      yl)-thiazolidin-4-ones has been analyzed with different topological descriptors
      obtained from DRAGON software. Here, simple topological descriptors (TOPO),
      Galvez topological charge indices (GVZ) and 2D autocorrelation descriptors
      (2DAUTO) have been found to yield good predictive models for the activity of
      these compounds. The correlations obtained from the TOPO class descriptors
      suggest that less extended or compact saturated structural templates would be
      better for the activity. The participating GVZ class descriptors suggest that
      they have same degree of influence on the activity. In 2DAUTO class, the large
      participation of descriptors of lags seven and three indicate the association of
      activity information with the seven and three centered structural fragments of
      these compounds. The physicochemical weighting components of these descriptors
      suggest homogeneous influence of mass, volume, electronegativity and/ or
      polarizability on the activity.

PMID- 16101583
TI  - Synthesis and QSAR studies on thiazolidinones as anti-HIV agents.
AB  - Selected 4-thiazolidinone have been synthesized and tested as anti-HIV activity.
      The results of the in vitro tests showed that one of the compounds, 5, inhibited
      the enzyme at 0.204 microM concentration with minimal toxicity to MT-4 cell.
      Furthermore, the QSAR studies indicated the role of PMIZ, Ovality and Total
      energy content of the compounds in rationalizing the activity.

PMID- 16101584
TI  - The sieve ratio for characterization and similarity analysis of DNA sequences.
AB  - A DNA sequence is a finite sequence of letters in the 4-letter DNA alphabet sigma
      = [A, C, G, T]. A set of condensed matrices was constructed to represent DNA
      sequences based on the sieve ratios of trinucleotide in sequence. Then, leading
      eigenvalues of these matrices were computed and considered as invariants for the
      DNA sequences. Similarity and dissimilarity analysis based on condensed matrices
      are given for eleven exon-1 genes of beta-globins of eleven species.

PMID- 16101585
TI  - The effect of N-terminal truncation on double-dimer assembly of goose delta
      crystallin.
AB  - Delta-crystallin is a soluble structural protein in avian eye lenses that confers
      special refractive properties. In the presence of GdmCl (guanidinium chloride),
      tetrameric delta-crystallin undergoes dissociation via a dimeric state to a
      monomeric molten globule intermediate state. The latter are denatured at higher
      GdmCl concentrations in a multi-state manner. In the present study, the X-ray
      structure of goose delta-crystallin was determined to 2.8 A (1 A=0.1 nm). In this
      structure the first 25 N-terminal residues interact with a hydrophobic cavity in
      a neighbouring molecule, stabilizing the quaternary structure of this protein.
      When these 25 residues were deleted this did not produce any gross structural
      changes, as judged by CD analysis, but slightly altered tryptophan fluorescence
      and ANS (8-anilino-1-naphthalenesulphonic acid) spectra. The dimeric form was
      significantly identified as judged by sedimentation velocity and nondenaturing
      gradient gel electrophoresis. This mutant had increased sensitivity to
      temperature denaturation and GdmCl concentrations of 0.3-1.0 M. This protein was
      destabilized about 3.3 kcal/mol (1 kcal=4.184 kJ) due to N-terminal truncation.
      After incubation at 37 degrees C N-terminal truncated proteins were prone to
      aggregation, suggesting the presence of the unstable dimeric conformation. An
      important role for the N-terminus in dimer assembly of goose delta-crystallin is
      proposed.

PMID- 16101586
TI  - SMAD 8 binding to mice Msx1 basal promoter is required for transcriptional
      activation.
AB  - The Msx1 gene in mice has been proven to be induced by BMP (bone morphogenetic
      protein) proteins, and three binding sites for SMAD, an intracellular BMP
      signalling transducer, have already been identified in its promoter. Gel shift
      analyses were performed and they demonstrated that the consensus found very near
      the transcription start site, a region designed BP (basal promoter), is
      functional for binding nuclear proteins from 10.5, 11.5 and 13.5 dpc (days post
      coitum) embryos. Notably, this binding occurs only when the SMAD-binding
      consensus sequence is maintained, suggesting that it is required for the
      formation of a protein complex over BP. Binding of purified SMAD 1 and SMAD 4 as
      well as supershift assay with SMAD 1/SMAD 5/SMAD 8 antibody proved that a SMAD
      protein is present in this complex. Transfection assays in cell cultures with
      fragments from BP driving the expression of luciferase confirmed that only in the
      presence of the SMAD consensus site is Msx1 expression activated. A proteomic
      analysis of the complex components after immunoprecipitation identified several
      proteins necessary to activate transcription including SMAD 8. Our results
      suggest that BMP2/BMP4 signalling through SMAD 8 is required for transcriptional
      activation of the mouse Msx1 gene.

PMID- 16101587
TI  - A multivalent recombinant antibody fragment specific for carcinoembryonic
      antigen.
AB  - In the present paper we report the development of a bivalent scFv (single-chain
      Fv) antibody fragment, starting from a mouse mAb (monoclonal antibody) specific
      for CEA (carcinoembryonic antigen) that has received approval for in vivo
      radioimmunodiagnosis in humans. The diabody is well expressed in Escherichia
      coli, is easily purified by a combination of immobilized metal ion affinity
      chromatography and gel filtration and exhibits high affinity and specificity for
      CEA, comparable with those of the original mAb. Biodistribution experiments in
      athymic nude mice transplanted with human CEA+ cancer cells showed that the 125I
      labelled diabody preferentially localizes in the tumour tissue and that retention
      is still high 48 h after injection. The diabody can be advantageous for some in
      vivo tumour targeting applications, due to the faster clearance derived from its
      smaller molecular mass.

PMID- 16101589
TI  - Improving the experience of birth in poor communities.

PMID- 16101590
TI  - Who will do the caesareans when there is no doctor? Finding creative solutions to
      the human resource crisis.

PMID- 16101591
TI  - Community interventions for maternal and perinatal health.

PMID- 16101592
TI  - The importance of fertility treatment in the developing world.

PMID- 16101593
TI  - The silent burden of gynaecological disease in low income countries.

PMID- 16101594
TI  - Current strategies for the reduction of maternal mortality.
AB  - The purpose of this article is to review current strategies for the reduction of
      maternal mortality and the evidence pertinent to these strategies. Historical,
      contextual and current literature were examined to identify the evidence base
      upon which recommendations on current strategies to reduce maternal mortality are
      made. Current safe motherhood strategies are designed based mostly on low grade
      evidence which is historical and observational, as well as on experience and a
      process of deductive reasoning. Safe motherhood strategies are complex public
      health approaches which are different from single clinical interventions. The
      approach to evidence used for clinical decision making needs to be reconsidered
      to fit with the practicalities of research on the effectiveness of strategies at
      the population level. It is unlikely that any single strategy will be optimal for
      different situations. Strengthening of the knowledge base on the effectiveness of
      public health strategies to reduce maternal mortality is urgently required but
      will need concerted action and international commitment.

PMID- 16101595
TI  - Malaria in pregnancy.
AB  - Malaria in pregnancy is one of the major causes of maternal morbidity worldwide,
      and leads to poor birth outcomes. There is a complex interaction between
      pregnancy and parasite-all favour the parasite and disadvantage the pregnant
      woman. Women who are semi-immune lose much of that immunity. They may present
      with placental malaria but with no parasites in their peripheral blood. A non
      immune pregnant women and her fetus are at serious risk from falciparum malaria.
      The diagnosis and management of malaria in pregnancy, including the safety of
      antimalarial drugs and interactions of malaria with HIV in pregnancy are
      reviewed.

PMID- 16101596
TI  - Preventing mother-to-child transmission of HIV: successes and challenges.
AB  - Mother-to-child transmission of HIV continues to be a major cause of infant
      morbidity and mortality in resource-poor settings. Intrapartum and postpartum
      nevirapine-based regimens have been introduced in many settings. New research has
      shown that better efficacy can be achieved with the addition of single-dose
      nevirapine to short course zidovudine regimens, and that selection of nevirapine
      resistant virus can be reduced with a short postpartum combination antiretroviral
      cover. Women who need antiretroviral therapy for their own health should receive
      it in pregnancy, and access for pregnant women needs to be expanded urgently. The
      reduction of transmission through breastfeeding remains a challenge.

PMID- 16101597
TI  - The prevention of cervical cancer in developing countries.
AB  - Cervical cancer remains the commonest cancer cause of death among women in
      developing countries, largely due to the failure to establish cytologically based
      cervical cancer screening programmes. There are many barriers to the
      establishment of screening programmes in poor countries ranging from limited
      financial, human and health resources to the complex infrastructural requirements
      of traditional screening programmes. Alternative approaches to cervical cancer
      prevention are currently being investigated, including primary prevention with
      prophylactic vaccines against human papillomavirus to alternative screening tests
      and protocols. These will be explored in this review.

PMID- 16101598
TI  - Appropriate technology to prevent maternal mortality: current research
      requirements.
AB  - Maternal mortality involves a complex mixture of clinical, infrastructural and
      social issues and will require a multifaceted approach if we are to see
      meaningful reductions occur. That includes thoughtful attention to appropriate
      technologies for low-resource countries. An international group of specialists
      meeting in Bellagio, Italy, in 2003 identified important needs and opportunities
      related to new and underutilized technologies to reduce pregnancy-related
      mortality. Research to fill in critical information gaps was a recurrent theme.
      Research, whether it is for product development, for building the evidence base
      about effectiveness and safety or for helping refine introduction strategies and
      guide practice, plays a critical role in the development and widespread use of
      technologies. Priority research needs related to the five major causes of
      maternal mortality-haemorrhage, puerperal sepsis, unsafe abortion, pre-eclampsia
      and eclampsia and obstructed labour-have been identified. Appropriate
      collaborations of investigators and other stakeholders and adequate financial
      resources are urgently needed to move the research agenda forward.

PMID- 16101599
TI  - Obstetric first aid: time for resuscitation.

PMID- 16101600
TI  - WHO systematic review of maternal mortality and morbidity: the prevalence of
      uterine rupture.
AB  - OBJECTIVE: To determine the prevalence of uterine rupture worldwide. DESIGN:
      Systematic review of all available data since 1990. SETTING: Community-based and
      facility-based reports from urban and rural studies worldwide. Sample Eighty
      three reports of uterine rupture rates are included in the systematic review.
      Most are facility based using cross-sectional study designs. METHODS: Following a
      pre-defined protocol an extensive search was conducted of 10 electronic databases
      as well as other sources. Articles were evaluated according to specified
      inclusion criteria. Uterine rupture data were collected along with information on
      the quality of reporting including definitions and identification of cases. Data
      were entered into a database and tabulated using SAS software. MAIN OUTCOME
      MEASURES: Prevalence of uterine rupture by country, period, study design,
      setting, participants, facility type and data source. RESULTS: Prevalence figures
      for uterine rupture were available for 86 groups of women. For unselected
      pregnant women, the prevalence of uterine rupture reported was considerably lower
      for community-based (median 0.053, range 0.016-0.30%) than for facility-based
      studies (0.31, 0.012-2.9%). The prevalence tended to be lower for countries
      defined by the United Nations as developed than the less or least developed
      countries. For women with previous caesarean section, the prevalence of uterine
      rupture reported was in the region of 1%. Only one report gave a prevalence for
      women without previous caesarean section, from a developed country, and this was
      extremely low (0.006%). CONCLUSION: In less and least developed countries,
      uterine rupture is more prevalent than in developed countries. In developed
      countries most uterine ruptures follow caesarean section. Future research on the
      prevalence of uterine rupture should differentiate between uterine rupture with
      and without previous caesarean section.

PMID- 16101601
TI  - The magnitude of abortion complications in Kenya.
AB  - OBJECTIVE: To estimate and describe the magnitude of abortion complications
      presenting at public hospitals in Kenya. DESIGN: Cross-sectional descriptive
      study. SETTING: Hospital-based. Population Records of all women presenting prior
      to 22 weeks of gestation with abortion-related complications at selected
      hospitals during a three-week study period. All public tertiary and provincial
      hospitals were included; stratified random sampling was employed to select a
      subset of 54 district hospitals nationwide. METHODS: Data collectors identified
      809 patients with abortion complications on all hospital wards and completed a
      standardised questionnaire for each by extracting information from the patient's
      hospital record. MAIN OUTCOME MEASURES: Incidence, aetiology, morbidity and
      mortality of abortion complications. RESULTS: Most women (80%) presented with
      incomplete abortion. Approximately 34% of the women had reached the second
      trimester of pregnancy. Adolescents (14-19 years old) accounted for approximately
      16% of the study sample. Manual vacuum aspiration was used to manage 80% of first
      trimester cases. The projected annual number of women with abortion complications
      admitted to public hospitals in Kenya is 20,893. The case fatality rate was
      estimated to be 0.87% (95% CI 0.71-1.02%), so an estimated 182 (95% CI 148-213)
      of these women die annually. The annual incidence of incomplete abortion and
      other abortion-related complications per 1000 women aged 15 to 49 years is
      projected to be 3.03. CONCLUSIONS: The high rate of abortion-related morbidity
      and mortality documented in the study highlights the critical need to address the
      issue of unsafe abortion in Kenya.

PMID- 16101602
TI  - Why are women still aborting outside designated facilities in metropolitan South
      Africa?
AB  - OBJECTIVE: To explore why South African women still abort outside designated
      services where there is substantial legal service provision. DESIGN: Descriptive
      study. SETTING: Three hospitals in Gauteng Province in South Africa. Sample Forty
      six women attending hospital with incomplete abortion who had abortions induced
      outside of designated facilities. METHODS: An interviewer-administered
      questionnaire with open and closed questions was completed. Induction status was
      determined from answers to a set of closed questions. Open-ended questions
      explored the circumstances of induction. Main focus of interviews Methods of
      induction used, barriers to legal service use. RESULTS: Nearly two-thirds of
      women (n= 38) had self-induced or had consulted a traditional healer. A minority
      of these women (n= 11) indicated that they did this because they experienced
      barriers to legal service use. For others it was presented as a 'natural'
      response to a health problem (unwanted pregnancy). Several women (n= 10) were
      given misoprostol by a doctor, nurse, or pharmacist. Fifty-four percent of the
      women had not used legal services because they did not know about the law, while
      15% knew of their legal rights, but did not know of a legal facility. Others did
      know where to access legal services but feared rude staff (17%) or breaches of
      confidentiality (6.5%). Others (6.5%) had been unable to get a legal abortion
      early enough in pregnancy to comply with the law. CONCLUSIONS: Lack of
      information on abortion rights under the Act and perceived poor quality of
      designated facilities were the most important barriers to access and should be
      addressed by policymakers and health service management. The willingness of women
      to self-medicate and visit traditional healers in these circumstances may
      influence the overall ability of the new legislation to reduce abortion
      morbidity.

PMID- 16101603
TI  - Violence against pregnant women: prevalence and characteristics. A population
      based study in Nicaragua.
AB  - OBJECTIVE: This study aims to estimate the prevalence and characteristics of
      partner abuse during pregnancy as well as to investigate associated social
      factors in Leon, Nicaragua. DESIGN: Cross-sectional community-based study.
      SETTING: All pregnant women from 50 randomly selected geographical clusters out
      of 208 in the municipality of Leon, Nicaragua. SAMPLE: A total of 478 pregnant
      women were included; only one woman refused to participate. METHOD: The domestic
      violence questionnaire from the WHO-co-ordinated Multi-Country Study on Women's
      Health and Life Events was used with each participant being interviewed twice
      during pregnancy. MAIN OUTCOME MEASURES: Prevalence and characteristics of
      partner violence during pregnancy. RESULTS: The prevalence of emotional, physical
      and sexual abuse during pregnancy was 32.4%, 13.4% and 6.7%, respectively.
      Seventeen percent reported experience of all three forms of violence. Two-thirds
      of the victims reported repeated abuse. Half of the abused women had experienced
      punches and kicks directed towards the abdomen and 93% had been injured. Most
      women had not sought health care in relation to the abuse, but those who did were
      usually hospitalised. Factors such as women's age below 20 years, poor access to
      social resources and high levels of emotional distress were independently
      associated with violence during pregnancy. CONCLUSION: Violence against pregnant
      women in Nicaragua is common and often repeated. Although these women have poor
      access to social resources and high levels of emotional distress, they are rarely
      assisted by the health services. Innovative strategies are needed to provide
      support and counselling.

PMID- 16101604
TI  - A randomised controlled trial of empowerment training for Chinese abused pregnant
      women in Hong Kong.
AB  - OBJECTIVE: To evaluate the effectiveness of an empowerment intervention in
      reducing intimate partner violence (IPV) and improving health status. DESIGN:
      Randomised controlled trial. SETTING: Antenatal clinic in a public hospital in
      Hong Kong. SAMPLE: One hundred and ten Chinese pregnant women with a history of
      abuse by their intimate partners. METHODS: Women were randomised to the
      experimental or control group. Experimental group women received empowerment
      training specially designed for Chinese abused pregnant women while the control
      group women received standard care for abused women. Data were collected at study
      entry and six weeks postnatal. MAIN OUTCOMES MEASURES: IPV [on the Conflict
      Tactics Scale (CTS)], health-related quality of life (SF-36) and postnatal
      depression [Edinburgh Postnatal Depression Scale (EPDS)]. RESULTS: Following the
      training, the experimental group had significantly higher physical functioning
      and had significantly improved role limitation due to physical problems and
      emotional problems. They also reported less psychological (but not sexual) abuse,
      minor (but not severe) physical violence and had significantly lower postnatal
      depression scores. However, they reported more bodily pain. CONCLUSION: An
      empowerment intervention specially designed for Chinese abused pregnant women was
      effective in reducing IPV and improving the health status of the women.

PMID- 16101605
TI  - A 50-year audit of maternal mortality in the Peninsula Maternal and Neonatal
      Service, Cape Town (1953-2002).
AB  - OBJECTIVE: To audit trends in maternal mortality in the Peninsula Maternal and
      Neonatal Service (PMNS) over a 50-year period, with respect to rates and patterns
      of causation. DESIGN: Retrospective and prospective audit. SETTING: The PMNS, an
      integrated perinatal service composed of primary, secondary and tertiary
      facilities in Cape Town. Population All women giving birth in the area of the
      Cape Peninsula served by the PMNS over the 50-year period. METHODS: Data on
      maternal deaths were collected for 1953-2002 inclusive, from annual obstetric and
      gynaecological reports. Three triennia (1954-1956, 1981-1983 and 1999-2001) were
      selected for a detailed comparison of trends in rates and causes of death. MAIN
      OUTCOME MEASURES: Maternal mortality rates (MMRs). Causes of maternal deaths.
      RESULTS: Total deliveries increased from 7315 in 1953 to 27,575 in 2002. The MMR
      declined from 301 deaths per 100,000 deliveries in 1953 to 31.2 in the triennium,
      1987-1989. From 1999, the MMR increased, reaching 112 in 2002. Comparing 1954
      1956 (MMR of 253.9) with 1981-1983 (MMR of 43.8), there was a marked decline in
      the MMR related to hypertension (80.4 to 11.3), haemorrhage (50.8 to 4.2),
      abortion (55 to 4.2), suspected pulmonary embolism (25.4 to 2.8), pregnancy
      related sepsis (8.5 to 4.2) and cardiac disease (21.2 to 2.8). Comparing 1981
      1983 (MMR of 43.8) with 1999-2001 (MMR of 59.4), there was a decline in the MMR
      associated with abortion (4.2 to 0). The MMR for haemorrhage, suspected pulmonary
      embolism and cardiac disease remained the same. There was a slight increase in
      the MMR attributed to hypertension (11.3 to 14.5) and pregnancy-related sepsis
      (4.2 to 7.3). There was a marked increase in the MMR associated with non
      pregnancy-related infections/AIDS (4.2 to 18.2). CONCLUSIONS: The MMR for all
      causes of maternal death declined significantly from 1953 to 1981 as a result of
      several interventions. From 1999, there has been a non-significant increase in
      MMR, predominantly due to the burden of HIV/AIDS-related mortality.

PMID- 16101606
TI  - Emergency obstetric care in developing countries: impact of guidelines
      implementation in a community hospital in Senegal.
AB  - OBJECTIVE: To evaluate, with volunteer professionals in a resource-poor setting,
      an approach of audit and feedback to promote local implementation of emergency
      obstetric guidelines. DESIGN: Triple cohort observational time series study.
      SETTING: A 46-bed obstetric unit in an academic-affiliated community hospital in
      Senegal. POPULATION: All pregnant women with haemorrhagic and hypertensive
      complications who were admitted to the maternity unit during the study periods.
      METHODS: To assess the benefits of guidelines implementation, maternal outcomes
      during the intervention period were compared with those occurring in two one-year
      periods when staff daily supervision was the main potentially effective action on
      clinical management. MAIN OUTCOME MEASURES: The intervention strategy was
      criteria-based audits with regular feedback over a one-year period. The clinical
      focus was haemorrhage and hypertension the most frequent causes of maternal death
      in the study population. Hospital charts were audited by external reviewers. The
      primary outcome was the case fatality rate (CFR) among patients with haemorrhage
      and hypertension. RESULTS: There was an increase in morbidity diagnoses during
      the intervention period. In addition, there was a marked increase in obstetric
      interventions, especially for transfusions and caesarean deliveries. Patients
      characteristic-adjusted case fatality decreased by 53% between baselines I and II
      and during the intervention period by 33% and 24%, compared with baseline periods
      I and II, respectively. Outcome improvements were different for haemorrhage and
      hypertension. CONCLUSION: While staff daily supervision may have improved
      maternal outcome before the intervention period, audit and feedback produced
      marked effects on emergency obstetric care, specially for complications requiring
      highly trained management (e.g. pre-eclampsia). Audit and feedback are one of the
      potentially effective guidelines implementation strategies that should be
      considered for further studies in resource-poor health facilities.

PMID- 16101607
TI  - Routines in facility-based maternity care: evidence from the Arab World.
AB  - OBJECTIVES: To document facility-based practices for normal labour and delivery
      in Egypt, Lebanon, the West Bank (part of the Occupied Palestinian Territory) and
      Syria and to categorise common findings according to evidence-based obstetrics.
      DESIGN: Three studies (Lebanon, West Bank and Syria) interviewed a key informant
      (providers) in maternity facilities. The study in Egypt directly observed
      individual labouring women. SETTING: Maternity wards. SAMPLE: Nationally
      representative sample of hospitals drawn in Lebanon and Syria. In the West Bank,
      a convenience sample of hospitals was used. In Egypt, the largest teaching
      hospital's maternity ward was observed. METHODS: Shared practices were
      categorised by adapting the World Health Organization's (WHO) 2004 classification
      of practices for normal birth into the following: practices known to be
      beneficial, practices likely to be beneficial, practices unlikely to be
      beneficial and practices likely to be ineffective or harmful. MAIN OUTCOME
      MEASURES: Routine hospital practices for normal labor and delivery. RESULTS:
      There was infrequent use of beneficial practices that should be encouraged and an
      unexpectedly high level of harmful practices that should be eliminated. Some
      beneficial practices were applied inappropriately and practices of unproven
      benefit were also documented. Some documented childbirth practices are
      potentially harmful to mothers and their babies. CONCLUSION: Facility practices
      for normal labour were largely not in accordance with the WHO evidence-based
      classification of practices for normal birth. The findings are worrying given the
      increasing proportion of facility-based births in the region and the improved but
      relatively high maternal and neonatal mortality ratios in these countries.
      Obstacles to following evidence-based protocols for normal labour require
      examination.

PMID- 16101608
TI  - Misoprostol in the management of the third stage of labour in the home delivery
      setting in rural Gambia: a randomised controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of 600 microg oral misoprostol on
      postpartum haemorrhage (PPH) and postpartum anaemia in a low income country home
      birth situation. DESIGN: Double blind randomised controlled trial. SETTING:
      Twenty-six villages in rural Gambia with 52 traditional birth attendants (TBAs).
      SAMPLE: One thousand, two hundred and twenty-nine women delivering at home under
      the guidance of a trained TBA. METHODS: Active management of the third stage of
      labour using three 200-microg misoprostol tablets and placebo or four 0.5-mg
      ergometrine tablets (standard treatment) and placebo. Tablets were taken orally
      immediately after delivery. MAIN OUTCOME MEASURES: Measured blood loss,
      postpartum haemoglobin (Hb), difference between Hb at the last antenatal care
      visit and three to five days postpartum. RESULTS: The misoprostol group
      experienced lower incidence of measured blood loss > or =500 mL and postpartum Hb
      <8 g/dL, but the differences were not statistically significant. The reduction in
      postpartum (compared with pre-delivery) Hb > or = 2 g/dL was 16.4% with
      misoprostol and 21.2% with ergometrine [relative risk 0.77; 95% confidence
      interval (CI) 0.60-0.98; P= 0.02]. Shivering was significantly more common with
      misoprostol, while vomiting was more common with ergometrine. Only transient side
      effects were observed. CONCLUSIONS: Six hundred micrograms of oral misoprostol is
      a promising drug to prevent life-threatening PPH in this setting.

PMID- 16101609
TI  - Misoprostol versus expectant management in premature rupture of membranes at
      term.
AB  - OBJECTIVE: To compare the effectiveness of immediate induction of labour with
      vaginal misoprostol versus expectant management for 24 hours followed by oxytocin
      induction in women with premature rupture of membranes at term (term PROM).
      DESIGN: An open, randomised, controlled trial. SETTING: Public university
      hospital in Campinas City, Brazil. POPULATION: One hundred and fifty pregnancies,
      half of them allocated to each group. METHODS: Statistical analysis used
      Student's t test, the chi2 test, Fisher's exact test, survival analysis and risk
      ratio estimates with 95% CI. MAIN OUTCOME MEASURES: Latency period, recruitment
      to delivery period, period of hospitalisation, mode of delivery, contractility
      pattern, fetal wellbeing, labour and delivery complications, neonatal and
      maternal morbidity. RESULTS: Both groups had similar general characteristics, but
      the misoprostol group had a significantly shorter latency period (9.4 vs 15.8
      hours), a shorter time interval from recruitment to delivery (18.9 vs 27.5
      hours), a shorter period of maternal hospitalisation and a slightly higher
      proportion of alterations of contractility when compared with the expectant
      group. Caesarean section rates were 20% in the misoprostol group and 30.7% in the
      other. There were no differences between them regarding fetal wellbeing,
      complications during labour and delivery and neonatal or postpartum maternal
      morbidity. Within 24 hours, 44% of women had delivered in the expectant group
      against 73.3% in the misoprostol group. CONCLUSIONS: Immediate labour induction
      with misoprostol in cases of term PROM shortens the latency period, the total
      time between recruitment to delivery and the time of maternal hospitalisation,
      increasing the occurrence of alterations of contractility without any maternal
      and perinatal outcomes disadvantages.

PMID- 16101610
TI  - Misoprostol and declining abortion-related morbidity in Santo Domingo, Dominican
      Republic: a temporal association.
AB  - OBJECTIVE: To validate anecdotal reports that abortion-related complications
      decreased in the Dominican Republic after the introduction of misoprostol into
      the country. DESIGN: Retrospective records reviews and cross-sectional surveys,
      interviews and focus groups. SETTING: Family planning clinics, pharmacies, door
      to-door canvassing and a tertiary care maternity hospital in Santo Domingo,
      Dominican Republic. POPULATION: Women of reproductive age in Santo Domingo,
      Dominican Republic. METHODS: Qualitative and quantitative methods were used.
      Individual interviews and focus groups of reproductive health professionals, non
      governmental organisation leaders and women's group leaders (n= 50) were
      conducted to discover the role of misoprostol in the Dominican Republic. Local
      women (n= 157) were surveyed to determine their knowledge of misoprostol as an
      abortifacient and mystery client visits were made to 80 pharmacies in order to
      purchase misoprostol without a prescription. Sales data were obtained that
      documented when misoprostol was introduced to the Dominican Republic pharmacies.
      Hospital admissions for abortions from the prior eight years were reviewed and
      hospital emergency room consultation ledgers of 31,190 visits for the period 1994
      2001 were reviewed for abortion complications. MAIN OUTCOME MEASURES: Frequencies
      of maternal morbidities and knowledge of misoprostol. RESULTS: Mystery clients
      purchased misoprostol without a prescription in nearly 64% of pharmacies; staff
      provided little additional information or counselling. Reliable sales data
      documented the introduction of misoprostol in 1986. Abortion complications
      decreased from 11.7% of abortions in 1986 to 1.7% in 2001. The majority of
      professionals interviewed felt that knowledge of these findings should be made
      public. CONCLUSIONS: The data were of too poor quality to validate the verbal
      reports reliably, but misoprostol appears to have been widely used over a period
      when abortion-related morbidity fell. It remains plausible that the use of
      misoprostol contributed to the reduction.

PMID- 16101611
TI  - A randomised controlled trial of 6 and 12 hourly administration of vaginal
      misoprostol for second trimester pregnancy termination.
AB  - OBJECTIVE: To compare the effectiveness of vaginal misoprostol administered 6 or
      12 hourly for second trimester pregnancy termination. DESIGN: A randomised
      controlled trial. SETTING: University teaching hospital. SAMPLE: Two hundred and
      seventy-nine pregnant women at gestations between 14 and 26 weeks undergoing
      pregnancy termination. METHODS: Women were randomised to receive 600-microg
      misoprostol tablets vaginally either every 6 hours or every 12 hours until
      abortion occurred. MAIN OUTCOME MEASURES: Induction-abortion interval, success
      rate within 24 and 48 hours and adverse effects. RESULTS: There was no
      significant difference in the median induction to abortion interval 6 hours (16
      hours) and 12 hours (16 hours; P= 0.80). The total dose of misoprostol was higher
      in the 6-hour group (1800 vs 1200 microg). The cumulative abortion rates within
      24 hours were 74% and 67% and within 48 hours 94% and 92%, in the 6- and 12-hour
      groups, respectively. Fever was more common in the 6-hour group (53%) versus the
      12-hour group (31%; P < 0.001). The incidence of nausea, vomiting, diarrhoea,
      severe bleeding and abdominal pain were similar. CONCLUSIONS: Misoprostol (600
      microg) administered at 12-hour intervals was associated with fewer adverse
      effects and was as effective as a 6-hour interval.

PMID- 16101612
TI  - Personal accounts of 'near-miss' maternal mortalities in Kampala, Uganda.
AB  - OBJECTIVE: To explore the socio-economic determinants of maternal mortality in
      Uganda through interviews with women who had 'near-misses'. DESIGN: Observational
      study using qualitative research methods. SETTING: The postnatal and gynaecology
      wards of a large government hospital in Kampala, Uganda. SAMPLE: Thirty women who
      had narrowly avoided maternal deaths with diagnoses of obstructed labour (7),
      severe pre-eclampsia/eclampsia (3), post caesarean infection (6), haemorrhage
      (5), ectopic pregnancy (5) and septic abortion (4). METHODS: The semi-structured
      interviews were conducted in the local language by a woman unconnected to the
      hospital, and were recorded before being translated and transcribed. Analysis was
      conducted in duplicate using commercial software. RESULTS: The predominant theme
      was powerlessness, which occurred both within and outside the hospital. It was
      evident in the women's attempts to get both practical and financial help from
      those around them as well as in their failure to gain rapid access to care.
      Financial barriers and problems with transport primarily governed health-seeking
      behaviour. Medical mistakes and delays in referral were evident in many
      interviews, especially in rural health centres. Women were appreciative of the
      care they received from the central government hospital, although there were
      reports of overcrowding, long delays, shortages and inhumane care. There were no
      reports of bribery. CONCLUSIONS: Women with near-miss maternal mortalities
      experience institutional and social powerlessness: these factors may be a major
      contributor to maternal mortality.

PMID- 16101613
TI  - Fecundity and pregnancy outcome in a cohort with sickle cell-haemoglobin C
      disease followed from birth.
AB  - OBJECTIVE: To compare pregnancy outcome in sickle cell-haemoglobin C (SC) disease
      with that in homozygous sickle cell (SS) disease and age-matched controls with a
      normal haemoglobin (AA) genotype. DESIGN: A cohort study followed from birth.
      SETTING: Sickle Cell Clinic, University Hospital and other Jamaican hospitals.
      POPULATION: Ninety-five pregnancies in 43 patients with SC disease, 94
      pregnancies in 52 patients with SS disease and 157 pregnancies in 68 controls.
      METHODS: Systematic review of all pregnancies occurring in sample population.
      Kaplan-Meier analysis for interval to first pregnancy, and the t test, chi2 test
      or Fisher's exact test as appropriate; correction was made for multiple testing
      and multiple linear regression was used for analysis of determinants of
      birthweight. MAIN OUTCOME MEASURES: Age at menarche, interval to first pregnancy,
      outcome of pregnancy, maternal complications and possible predictors of low
      birthweight. RESULTS: Menarche was marginally delayed in SC disease compared with
      AA controls (median age 13.7 vs 13.0 years, P= 0.02) but age at first pregnancy
      was similar (median age 22.5 vs 20.1 years, P= 0.32). Pregnancy outcome in SC
      disease did not differ from AA controls but compared with SS disease there were
      marginally fewer miscarriages, more live deliveries and greater birthweight. The
      prevalence of pregnancy-induced hypertension, pre-eclampsia, antepartum or
      postpartum haemorrhage in SC disease did not differ from AA controls but the
      prevalence of sickle-related complications was similar to SS disease.
      CONCLUSIONS: Contrary to some claims, pregnancy outcome in SC disease is
      generally benign compared with SS disease.

PMID- 16101614
TI  - A simple way to increase service use: triggers of women's uptake of postpartum
      services.
AB  - OBJECTIVE: To examine the socio-demographic and service-related determinants of
      utilisation of postpartum services. DESIGN: Data were used from a single-blind,
      randomised controlled trial aimed at changing women's knowledge, attitude and
      behaviour regarding certain postpartum health issues by providing written
      information via a specially prepared booklet. SETTING: Four private hospitals,
      two in Beirut and two in the Bekaa region, were selected. All were privately
      owned and one in Beirut was a teaching hospital. SAMPLE: All women delivering a
      live birth in the designated hospitals during a three- to four-month period were
      recruited into the study. Of the 503 eligible women, 450 agreed to complete the
      initial questionnaire and 378 completed the postpartum interviews. METHODS: Eight
      trained female interviewers collected the baseline data. On discharge,
      interviewers handed each woman a sealed and numbered envelope containing the
      intervention booklet or the placebo leaflets. Interviewers were blind about the
      allocation group of women. Interviewers conducted follow up assessment at women's
      residence 6-20 weeks after delivery. MAIN OUTCOME MEASURES: Any postpartum visit
      with or without a preset appointment. RESULTS: Multivariable analysis with
      adjusted ORs show that women given an appointment for their postpartum visit were
      more likely to having had that visit (OR = 6.8, 95% CI 6.2-7.4). In the absence
      of such an appointment, university education (OR = 3.6, 95% CI 2.6-4.7),
      information on maternal health (OR = 4.9, 95% CI 4.0-5.8) and the intervention
      booklet (OR = 2.9, 95% CI 2.0-3.9) were important determinants of a postpartum
      visit. CONCLUSION: Giving women appointments for postpartum visits, or written or
      verbal information on maternal health can increase their use of health services.

PMID- 16101615
TI  - Initial Asian experience in hysteroscopic sterilisation using the Essure
      permanent birth control device.
AB  - OBJECTIVE: To present our initial experience in the use of the Essure permanent
      birth control device in a predominately Asian population. DESIGN: A retrospective
      study. SETTING: Minimally Invasive Surgery Unit, KK Women's and Children's
      Hospital, Singapore. POPULATION: Eighty women seeking permanent birth control.
      METHODS: From 22 June 2001, women who sought sterilisation were counselled with
      regards to the various options of permanent birth control. Informed consent for
      hysteroscopic sterilisation was obtained only after the woman met the criteria
      for Essure permanent birth control. The sterilisation procedure was carried out
      without the need for general anaesthesia in a day surgery centre using the Essure
      permanent birth control device. The surgical details and post procedure follow up
      were analysed. MAIN OUTCOME MEASURES: Feasibility and safety of the Essure
      permanent birth control device in Asians and its non-placement rate. RESULTS: No
      serious adverse events or complications were encountered in using the Essure
      device. No pregnancies have been reported in our series to date. A significant
      reduction in the Essure device non-placement rate (20.0%vs 4.0%, P= 0.021) and
      mean operation time (27.3 vs 19.6 minutes, P= 0.006) were seen when patients were
      pre-medicated with spasmolytic agent and analgesia. CONCLUSIONS: The Essure
      permanent birth control device is safe and suitable for Asians. Its non-placement
      rate may be improved with pre-medication of spasmolytic agent and analgesia.

PMID- 16101616
TI  - Mental health screening in women with genital tract fistulae.
AB  - There is little information regarding the mental health status of women with
      genital tract fistulae in developing countries. The aim of this prospective
      observational study was to screen women at Dhaka Medical College Hospital,
      Bangladesh (December 2003 to June 2004), and Addis Ababa Fistula Hospital,
      Ethiopia (June to July 2004), with genital tract fistula for mental health
      dysfunction. Women presenting to the above institutions were screened using the
      General Health Questionnaire (GHQ-28) prior to fistula surgery. As the women were
      illiterate, the questionnaire was completed with the assistance of a medical
      officer, nurse or interpreter. The female staff members acted as controls. Sixty
      eight women with fistulae and 28 controls completed the GHQ-28. Sixty-six of the
      68 women with fistulae screened positive to probable mental health dysfunction
      compared with 9 of the 28 controls. We conclude that women with genital tract
      fistula are at high risk of mental health dysfunction. If the high rates of
      positive screening are confirmed on psychiatric evaluation, then the management
      of women with genital tract fistulas must include routine
      psychological/psychiatric assessment and treatment.

PMID- 16101617
TI  - Maternal death after intrapartum saline amnioinfusion--report of two cases.

PMID- 16101618
TI  - Ischaemic gangrene of the scalp in the neonate: a complication of obstructed
      labour.

PMID- 16101620
TI  - Multicenter, prospective, randomized safety and efficacy study of a new atrial
      based managed ventricular pacing mode (MVP) in dual chamber ICDs.
AB  - BACKGROUND: Ventricular desynchronization caused by right ventricular pacing may
      impair ventricular function and increase risk of heart failure (CHF), atrial
      fibrillation (AF), and death. Conventional DDD/R mode often results in high
      cumulative percentage ventricular pacing (Cum%VP). We hypothesized that a new
      managed ventricular pacing mode (MVP) would safely provide AAI/R pacing with
      ventricular monitoring and DDD/R during AV block (AVB) and reduce Cum%VP compared
      to DDD/R. METHODS: MVP RAMware was downloaded in 181 patients with Marquis DR
      ICDs. Patients were initially randomized to either MVP or DDD/R for 1 month, then
      crossed over to the opposite mode for 1 month. ICD diagnostics were analyzed for
      cumulative percentage atrial pacing (Cum%AP), Cum%VP, and duration of DDD/R
      pacing for spontaneous AVB. RESULTS: Baseline characteristics included age 66 +/-
      12 years, EF 36 +/- 14%, and NYHA Class II-III 36%. Baseline PR interval was 190
      +/- 53 msec and programmed AV intervals (DDD/R) were 216 +/- 50 (paced)/189 +/-
      53 (sensed) msec. Mean Cum%VP was significantly lower in MVP versus DDD/R (4.1 +/
      16.3 vs 73.8 +/- 32.5, P < 0.0001). The median absolute and relative reductions
      in Cum%VP during MVP were 85.0 and 99.9, respectively. Mean Cum%AP was not
      different between MVP versus DDD/R (48.7 +/- 38.5 vs 47.3 +/- 38.4, P = 0.83).
      During MVP overall time spent in AAI/R was 89.6% (intrinsic conduction), DDD/R
      6.7% (intermittent AVB), and DDI/R 3.7% (AF). No adverse events were attributed
      to MVP. CONCLUSIONS: MVP safely achieves functional atrial pacing by limiting
      ventricular pacing to periods of intermittent AVB and AF in ICD patients,
      significantly reducing Cum%VP compared to DDD/R. MVP is a universal pacing mode
      that adapts to AVB and AF, providing both atrial pacing and ventricular pacing
      support when needed.

PMID- 16101621
TI  - Comparison of induced and spontaneous atrial tachyarrhythmias in patients with a
      history of spontaneous atrial tachyarrhythmias.
AB  - INTRODUCTION: This retrospective study investigated whether induced episodes
      could be used to predict the morphology of future spontaneous atrial episodes.
      METHODS: Eighty-two patients (64 +/- 12 years; 77% male; CAD in 60%; left
      ventricular ejection fraction 45 +/- 16%) with a history of atrial tachycardia or
      atrial fibrillation (AT/AF) were implanted with a dual-chamber implantable
      cardioverter defibrillator (ICD) and followed for 6 months. A total of 224
      episodes of induced and spontaneous AT/AF were classified into type I, II, and
      III according to the method of Israel et al. and then compared based on average
      cycle length (CL) and atrial amplitude. Episodes were also grouped as "pace
      terminable" or "nonpace-terminable" based on the CL definition of Gillis et al.
      RESULTS: The analysis of 121 induced episodes (from 80 patients) and 103
      spontaneous episodes (from 43 patients) showed that within each arrhythmia type,
      there were no significant differences in CL or mean amplitude between induced and
      spontaneous episodes. Additional analysis of patients that had both induced and
      spontaneous episodes (n = 41) showed 78% had at least one spontaneous episode
      that matched the induced episode. Fifty-seven percent of spontaneous episodes
      were considered to be pace-terminable based on CL. CONCLUSIONS: Our data suggest
      that there is no significant difference between induced and spontaneous episodes
      of AT/AF of the same type. The majority of patients had at least one spontaneous
      episode of the same type as the induced episode, showing that induced atrial
      arrhythmias may be useful in predicting the morphology of future spontaneous
      episodes and in identifying patients potentially benefiting from atrial
      antitachycardia pacing.

PMID- 16101622
TI  - Spatial resolution of pacemapping and activation mapping in patients with
      idiopathic right ventricular outflow tract tachycardia.
AB  - BACKGROUND: The purpose of this study was to compare the spatial resolution of
      activation mapping and pacemapping in patients undergoing ablation of idiopathic
      ventricular tachycardia (VT) arising from the right ventricular outflow tract
      (RVOT). A direct comparison of the two techniques has not been undertaken.
      METHODS AND RESULTS: Electroanatomical activation maps of the RVOT were obtained
      during VT in 15 patients. Pacemaps were obtained from multiple sites, tagged on
      the activation map, and scored according the degree of concordance between the
      paced QRS configuration and that of VT. The site of successful ablation was
      considered the VT site of origin. Initial endocardial activation away from the
      site of origin was rapid; the mean area of myocardium activated within the first
      10 msec (early activation area, EAA) was 3.0 +/- 1.6 cm(2) (range: 1.3-6.4
      cm(2)). Best pacemap scores were always obtained adjacent to the site of origin.
      Pacemap concordance, and the probability of an exact pacemap match significantly
      decreased with increasing distance of the pacing site from the site of origin (P
      < 0.01). All patients had more than one pacing site yielding a best pacemap
      score. The greatest distance between such sites in an individual patient ranged
      from 11 to 26 mm (mean: 18 +/- 5 mm), and was strongly correlated with the size
      of the EAA (r = 0.77, P < 0.001). CONCLUSIONS: Pacemapping and activation mapping
      provide similar localizing information. The spatial resolution of each technique
      is modest, varies between patients, and may be optimized by three-dimensional
      data display.

PMID- 16101623
TI  - Implications and outcome of permanent coronary sinus lead extraction and
      reimplantation.
AB  - OBJECTIVE: We examined the implications and outcome of coronary sinus (CS) lead
      removal including the feasibility of laser use within the CS. BACKGROUND: Cardiac
      anatomy and lead interactions are more complex with the advent of biventricular
      pacemakers and atrial cardioverters requiring permanent lead/shocking coil
      placement in the coronary sinus and its branches. METHODS: Fifty-five permanent
      cardiac leads were extracted during 2003 in 28 consecutive patients. Our study
      population included a 10/55 (18%) subset (all males; age 73 +/- 6 years; EF =
      0.24 +/- 0.09) that underwent CS (1/10) or vein branch (9/10) lead extraction.
      Leads were extracted with an excimer laser sheath (n = 4) or by direct traction
      (n = 6). Median times between implantation and lead removal were 9.5 months
      (range 5-59) in the laser group and 3 months (range 3-4) in the direct traction
      group. Indication for extraction was infection (n = 4), dislodgement (n = 3),
      diaphragm stimulation (n = 2), and elevated threshold (n = 1). The CS was divided
      into distal, mid, and proximal segments by venogram. RESULTS: Entry of the laser
      sheath into the CS was necessary in three of four laser patients. The two distal
      CS laser cases (left lateral CS coil and anterior-lateral left ventricular (LV)
      lead) required both 14- and 12-Fr sheaths, separately. The proximal CS laser case
      (posterior-lateral LV lead) required a 12 Fr sheath. The remaining laser patient
      required a 12-Fr sheath to pass to the mid SVC. There were no procedural
      complications as a result of CS lead extraction. Reimplantation of a CS lead was
      attempted in 7/10 patients at a median of 4 days (range 1-300). CS venograms were
      available for review in patients before initial implantation (6/10) and after
      extraction (7/10). The postextraction venograms demonstrated complete occlusion
      of the vein from which the lead was extracted, and its distal branches, which
      were unusable in 5/10 (50%). The vein occlusions were present in patients with
      indwelling leads for greater than 3 months and were independent of extraction
      method. CONCLUSIONS: Laser lead extraction in the coronary sinus appears feasible
      in carefully selected cases with mandatory indications. However, special
      intraoperative monitoring and echocardiographic imaging with surgical backup
      ready is strongly recommended. Target vein selection may be limited for the
      purpose of reimplantation when leads are indwelling for greater than 3 months.

PMID- 16101624
TI  - Surface atrial frequency analysis in patients with atrial fibrillation: assessing
      the effects of linear left atrial ablation.
AB  - INTRODUCTION: Our group has shown previously that measurements of atrial
      frequency can be obtained from surface 12-lead ECG recordings of patients during
      atrial fibrillation (AF), using a combination of principal component and Fourier
      transform algorithms. Such measurements are reproducible over time and change
      with drug manipulation of the arrhythmia. AIMS: To determine whether linear left
      atrial ablation, using a combination of "roof" and "mitral isthmus" lines results
      in changes in surface atrial frequency during AF and to assess the contribution
      of each individual line when sited sequentially. METHODS AND RESULTS:
      Computerized recordings from 26 patients, who had undergone linear ablation
      procedures for AF, were reviewed. The atrial signal was extracted from the 12
      lead ECG data by principal component analysis and the main frequency component
      identified using Fourier analysis. Atrial frequency before and after these two
      standard ablation lines was compared. Atrial frequency decreased significantly
      after the combination of roof and mitral isthmus lines (5.66 vs 5.15 Hz) and when
      either roof (5.61 vs 5.13 Hz) or mitral isthmus (5.89 vs 5.75 Hz) lines were
      sited first. However, only the roof line led to a significant reduction in atrial
      frequency when sited second (5.64 vs 5.49 Hz). CONCLUSIONS: Measurements of
      atrial frequency can be obtained from surface 12-lead ECG recordings during AF
      and change as predicted in response to linear left atrial ablation. This
      technique may be useful in assessing antiarrhythmic treatments for AF.

PMID- 16101625
TI  - Incidence and predictors of pulmonary vein stenosis following catheter ablation
      of atrial fibrillation using the anatomic pulmonary vein ablation approach:
      results from paired magnetic resonance imaging.
AB  - INTRODUCTION: There are currently no studies systematically evaluating pulmonary
      vein (PV) stenosis following catheter ablation of atrial fibrillation (AF) using
      the anatomic PV ablation approach. METHODS AND RESULTS: Forty-one patients with
      AF underwent anatomic PV ablation under the guidance of a three-dimensional
      electroanatomic mapping system. Gadolinium-enhanced magnetic resonance (MR)
      imaging was performed in all patients prior to and 8-10 weeks after ablation
      procedures for screening of PV stenosis. A PV stenosis was defined as a
      detectable (> or =3 mm) narrowing in PV diameter. The severity of stenosis was
      categorized as mild (<50% stenosis), moderate (50-70%), or severe (>70%). A total
      157 PVs were analyzed. A detectable PV narrowing was observed in 60 of 157 PVs
      (38%). The severity of stenosis was mild in 54 PVs (34%), moderate in five PVs
      (3.2%), and severe in one PV (0.6%). All mild PV stenoses displayed a concentric
      pattern. Moderate or severe PV stenosis was only observed in patients with an
      individual encircling lesion set. Multivariable analysis identified individual
      encircling lesion set and larger PV size as the independent predictors of
      detectable PV narrowing. All patients with PV stenosis were asymptomatic and none
      required treatment. CONCLUSIONS: The results of this study demonstrate that
      detectable PV narrowing occurs in 38% of PVs following anatomic PV ablation.
      Moderate or severe PV stenosis occurs in 3.8% of PVs. The high incidence of mild
      stenosis likely reflects reverse remodeling rather than pathological PV stenosis.
      The probability of moderate or severe PV stenosis appears to be related to
      creation of individual encircling rather than encircling in pairs lesion.

PMID- 16101626
TI  - Prolongation of atrial effective refractory period with biatrial nonexcitatory
      stimulation.
AB  - BACKGROUND: A nonexcitatory, nonpropagating atrial extrastimulus delivered in the
      refractory period of the preceding cycle can prolong the atrial effective
      refractory period (AERP) and prevent the induction of atrial fibrillation by
      another AE introduced in the vulnerable period. Whether the effect of this
      nonexcitatory stimulation (NE) is confined only to its application site is
      unknown. METHODS AND RESULTS: Sixteen consecutive patients were recruited into
      the study and 2 patients were excluded because of development of more sustained
      atrial fibrillation. NE was commenced by introduction of a 2.0 msec, 20-mA
      impulse at 50 msec after the preceding captured pacing impulse. AERP of right
      atrial septum, a distant site to NE application, was determined at baseline and
      after 5 minutes of steady pacing at six different protocols: protocol 1, 2, and 3
      were conventional pacing at high right atrium, distal coronary sinus, and
      biatrial sites, respectively, and protocol 4, 5, and 6 were conventional pacing
      together with NE applied to the same sites as protocol 1, 2, and 3. Biatrial NE
      (protocol 6 with median AERP = 212.5 msec) significantly prolonged AERP compared
      with baseline (median AERP = 202.5 msec and P < 0.05), conventional pacing
      (protocol 1, 2, and 3 with median AERP = 205.0 msec, 205.0 msec, and 205.0 msec,
      respectively, and all P < 0.05), and single-site NE (protocol 4 and 5 with median
      AERP = 207.5 msec and 207.5 msec, respectively, and both P < 0.05). CONCLUSION:
      Biatrial NE resulted in AERP prolongation even at sites distant to NE
      application. The study result suggests that by adding NE to multi-sites pacing
      for atrial fibrillation prevention may have additional benefit.

PMID- 16101627
TI  - Enhanced coagulation activation by in vitro lipopolysaccharide challenge in
      patients with ventricular fibrillation complicating acute myocardial infarction.
AB  - BACKGROUND: Indicators of coagulation and inflammation are elevated in patients
      with coronary heart disease. A role of coagulation activation in ventricular
      fibrillation during acute myocardial infarction has not been described. METHODS
      AND RESULTS: Whole blood samples of 21 patients with a history of acute
      myocardial infarction complicated by ventricular fibrillation and whole blood
      samples of 18 patients without ventricular fibrillation were incubated with
      lipopolysaccharide (LPS). In both groups, the in vitro blood coagulation time was
      measured with the ReoRox, a viscometric whole blood coagulometer. CD62P
      expression on platelets, tissue-factor binding on monocytes, and platelet
      monocyte aggregates were measured with flow cytometry. Without LPS, no difference
      in the coagulation times were observed in both patient groups. After incubation
      with LPS, patients with a history of ventricular fibrillation showed a
      significantly decreased coagulation time compared to patients without ventricular
      fibrillation. The decrease of coagulation time after incubation with LPS also
      differed significantly in both groups. Expression of CD62P on platelets was
      significantly higher in patients with a history of ventricular fibrillation after
      incubation with LPS. Although in each patient group incubation with LPS induced a
      significantly increased amount of tissue factor on monocytes and a significantly
      increased the number of platelet-monocyte aggregates, the two groups did not
      differ significantly concerning tissue factor binding on monocytes and the amount
      of platelet-monocyte aggregates. CONCLUSIONS: After in vitro LPS challenge,
      patients with a history of ventricular fibrillation during myocardial infarction
      show an enhanced coagulation activation, which may partly be due to an enhanced
      platelet activation.

PMID- 16101628
TI  - Regression analysis between heart rate variability and baroreflex-related vagus
      nerve activity in rats.
AB  - INTRODUCTION: Many previous studies have suggested that the high-frequency (HF)
      power of the heart rate variability may represent cardiac vagal activity although
      direct evidence of a correlation between the HF and vagal neuronal activity is
      still lacking. In the present study, we performed a regression analysis of the HF
      and vagal neurograms. METHODS AND RESULTS: Experiments were carried out on adult
      male Sprague-Dawley rats anesthetized with a continuous infusion of pentobarbital
      sodium. The baroreflex-related vagus neuronal activities were obtained by nerve
      or single-fiber recordings. The transient baroreflex response was employed to
      alter vagus neuronal activities using a bolus injection of phenylephrine (PE). On
      line power spectral analysis of the heart rate and a vagal neurogram was
      performed during the acute baroreflex response. During the test period, systemic
      arterial pressure immediately increased in response to the PE injection, after
      which the R-R interval (RR), HF (0.6-2.4 Hz), and vagus nerve and unit activities
      all dramatically increased. Both nerve and unit activities exhibited good
      correlations (r > or = 0.7 in all nerve recordings and r > or = 0.6 in 91% of
      single-fiber recordings) with the HF. There were insignificant differences
      between the right- and left-side baroreflex-related vagus nerve recordings.
      CONCLUSION: Our present study provides a direct linkage between the HF and vagus
      neuronal electrical activity in anesthetized rats.

PMID- 16101629
TI  - Vagal tone: myths and realities.

PMID- 16101630
TI  - Action potential duration and QT interval during pinacidil infusion in isolated
      rabbit hearts.
AB  - INTRODUCTION: Acute myocardial ischemia, which opens K(ATP) channel, is
      associated with shortened action potential duration (APD) but prolonged QT
      interval. This discrepancy has not been adequately explained. We hypothesize that
      the duration of intracellular calcium (Ca(i)) transient (DCaT) may play a role in
      determining QT interval. METHODS AND RESULTS: We performed simultaneous optical
      mapping of voltage and Ca(i) in 15 isolated rabbit hearts during a K(ATP) channel
      opener (pinacidil) infusion. Anterior epicardial mapping (n = 7) showed no
      difference of APD(90), QT interval, and the DCaT(90) at baseline. When perfused
      with 80 microM pinacidil, the APD(90), the QT interval, and the DCaT(90) were 105
      +/- 10 msec, 199 +/- 14 msec, and 189 +/- 13 msec, respectively, during right
      ventricular (RV) pacing (P < 0.05). Posterior epicardial mapping (n = 4) showed
      that the APD(90) was significantly (P < 0.05) shorter than QT interval and
      DCaT(90) during pinacidil infusion. The results of the transmural mapping studies
      (n = 4) showed that the QT interval during RV pacing was not different than the
      DCaT(90) in the epicardium, midmyocardium, and endocardium, but was significantly
      (P < 0.01) longer than the APD(90) in epicardium, midmyocardium, and endocardium,
      respectively. There was a good correlation between the DCaT(90) and QT interval
      at baseline (r = 0.92, P < 0.0001) and during pinacidil infusion (r = 0.74, P <
      0.0001). CONCLUSION: We conclude that K(ATP) channel opening shortened APD but
      not the QT interval. Because Ca(i) did not return to diastolic level at the end
      of action potential, it may have created a heterogeneous membrane potential
      distribution that determined the QT interval.

PMID- 16101631
TI  - Effects of pulmonary vein ablation on regional atrial vagal innervation and
      vulnerability to atrial fibrillation in dogs.
AB  - INTRODUCTION: Pulmonary vein (PV) isolation has proven to be an effective therapy
      for atrial fibrillation (AF). However, clinical evidence suggests that
      suppression of AF after PV isolation could not be fully attributed to the
      interruption of electrical conduction in and out of the PVs. Furthermore, little
      is known regarding the effects of ablation around the PVs on the atrial
      electrophysiological properties. We aimed to study the changes in atrial response
      to vagal stimulation (VS) after PV ablation (PVA). METHODS: We studied 11 adult
      mongrel dogs under general anesthesia. Bilateral cervical sympathovagal trunks
      were decentralized. Propranolol was given to block sympathetic effects.
      Multipolar catheters were placed into right atrial appendage (RAA), distal and
      proximal coronary sinus (CSD, CSP), and left atrial free wall (LAFW). PVA was
      performed via trans-septal approach. Atrial effective refractory period (AERP)
      and vulnerability window (VW) of AF were measured with and without VS before and
      after ablation to isolate the PVs. RESULTS: After ablation, AERP shortening in
      response to VS significantly decreased in the left atrium (43.64 +/- 21.57 vs
      11.82 +/- 9.82 msec, P < 0.001 at LAFW; 50.91 +/- 26.25 vs 11.82 +/- 14.01 msec,
      P < 0.001 at CSP; 50 +/- 31.94 vs 17.27 +/- 20.54 msec, P < 0.005 at CSD), while
      the response to VS did not change significantly at RAA (58.18 +/- 28.22 vs 50.91
      +/- 22.12 msec, P = 0.245). After ablation, atrial fibrillation VW during VS
      narrowed (20.63 +/- 11.48 vs 5.63 +/- 8.63 msec, P < 0.03 at LAFW; 26.25 +/-
      12.46 vs 5.00 +/- 9.64 msec, P = 0.001 at CSP; 28.75 +/- 18.47 vs 6.88 +/- 7.53
      msec, P < 0.02 at CSD, and 33.75 +/- 24.5 vs 16.25 +/- 9.91 msec, P = 0.03 at
      RAA). CONCLUSIONS: Ablation around the PV ostia diminishes left atrial response
      to VS and decreases the atrial VW. The attenuated vagal response after ablation
      may contribute to the suppression of AF.

PMID- 16101632
TI  - Parasympathetics and atrial fibrillation.

PMID- 16101633
TI  - Mechanisms for the maintenance of ventricular fibrillation: the nonuniform
      dispersion of refractoriness, restitution properties, or anatomic
      heterogeneities?
AB  - INTRODUCTION: The relative importance of nonuniform dispersion of refractoriness,
      steep restitution slopes, and anatomic heterogeneities in causing conduction
      block during ventricular fibrillation (VF) remains unknown. METHODS AND RESULTS:
      In six open-chest pigs, ventricular refractoriness and restitution curves were
      estimated from activation recovery intervals (ARIs) calculated from 504 (21 x 24)
      unipolar electrode recordings 2 mm apart in a plaque sutured to the left
      ventricular (LV) free wall. A steady-state restitution protocol was performed
      twice at each of two pacing sites: the LV base and near the left anterior
      descending artery. VF was electrically induced four times and the incidence of
      conduction block at each electrode during the first 20 seconds was determined by
      an automated algorithm. The gradient of the ARI was calculated at each electrode
      to estimate the spatial dispersion of refractoriness. An exponential curve was
      fit to the restitution plots of ARIs versus the corresponding diastolic intervals
      (DIs) for all pacing cycle lengths at each electrode. The locations of epicardial
      blood vessels were noted after the study. Spatial patterns of conduction block
      were significantly correlated between the four VF episodes in the same animal (r
      = 0.66 +/- 0.07, P < 0.05). At the shortest pacing cycle length, the spatial
      distribution of ARIs, ARI gradients, and restitution slopes was not random but
      formed clusters of similar values. However, none of these variables was
      significantly correlated with the incidence of conduction block, even though ARI
      gradients >2 msec/mm were present between many clusters and approximately 90% of
      restitution slopes were >1. Instead, conduction block frequently appeared to
      cluster along epicardial vessels. CONCLUSION: Neither the dispersion of
      refractoriness nor action potential duration restitution determined during rapid
      pacing by itself is the major determinant of the location of conduction block
      during early VF in normal pigs. It may be that these factors interact
      synergistically with each other as well as with other factors, including anatomic
      heterogeneities such as those caused by blood vessels, which may be particularly
      important for the formation of conduction block and maintenance of VF.

PMID- 16101634
TI  - Assessment of the proarrhythmic potential of the novel antiarrhythmic agent
      AZD7009 and dofetilide in experimental models of torsades de pointes.
AB  - BACKGROUND: This study examined the proarrhythmic potential of the novel
      antiarrhythmic agent AZD7009 and dofetilide. METHODS AND RESULTS: The
      electrophysiological and proarrhythmic effects of AZD7009 and dofetilide were
      assessed in the arterially perfused canine and rabbit left ventricular wedge
      preparation. The proarrhythmic potential of AZD7009, dofetilide, and azimilide
      was further assessed in the methoxamine-sensitized rabbit model of torsades de
      pointes (TdP) in vivo. AZD7009 lengthened the action potential duration (APD) and
      the QT interval in a bell-shaped manner (15.9 +/- 1.3% in canine wedge and 46.1
      +/- 2.9% in rabbit wedge) occurring at 3 and 1 microM. In contrast, dofetilide
      did not show the bell-shaped concentration response and the QT interval was
      lengthened more extensively (27.7 +/- 1.6% and 100.8 +/- 10.0%). Furthermore,
      whereas dofetilide prolonged the midmyocardial and endocardial APD predominantly,
      resulting in an increased transmural dispersion of repolarization (TDR), AZD7009
      prolonged the APD more homogenously in all cell layers. At 1 microM, AZD7009
      produced phase 2 early afterdepolarizations (EADs) in 1/4 rabbit preparations but
      without ventricular R-on-T extrasystoles or TdP. In contrast, starting at 0.03
      microM, dofetilide-induced EADs, R-on-T extrasystoles and TdP in 6/6, 5/6, and
      4/6 preparations. Following intravenous infusion of AZD7009 (210 nmol/kg/minute),
      dofetilide (2 nmol/kg/minute) or azimilide (3.33 micromol/kg/minute), TdP was
      induced in 0/8, 5/8, and 5/8 rabbits (P = 0.026 vs AZD7009), respectively. In 5/5
      rabbits, AZD7009 promptly suppressed TdP induced by dofetilide. CONCLUSIONS: In
      animal models of TdP, AZD7009 delays ventricular repolarization in a self-limited
      way associated with a low risk of repolarization-related proarrhythmia.

PMID- 16101635
TI  - Creating continuous linear lesions in the atria: a comparison of the multipolar
      ablation technique versus the conventional drag-and-burn.
AB  - INTRODUCTION: Catheter-based treatment of atrial fibrillation (AF) requires the
      isolation of the triggering foci as well as modification of the atria with
      substrate that sustains AF. The creation of linear lesions in the left atrium
      with standard radiofrequency ablative methods requires long procedural times with
      unpredictable results. METHODS: The simultaneous delivery of phase-shifted
      radiofrequency energy from a multipolar catheter was compared to the conventional
      drag-and-burn technique for creating linear lesions in 10 dogs. Four atrial sites
      were targeted under intracardiac ultrasound and fluoroscopic guidance in each of
      10 dogs. The conventional drag-and-burn technique or the multipolar phase-shifted
      ablation catheter was randomly applied for 60 seconds and compared. RESULTS:
      Creating linear lesions using the simultaneous multipolar phase-shifted ablation
      catheter was on average 11.0 minutes faster (33.6 minutes vs 44.6 minutes, P <
      0.01) than the drag-and-burn method. The fraction of the lesion length achieved
      using phase-shifted ablation compared to that intended was 23% greater (76% vs
      53%, P < 0.01), and has less discontinuities (0.1 compared to 0.8
      discontinuities/line, P < 0.003). There was no significant difference in either
      the lesion transmurality, or fluoroscopy times. CONCLUSION: The simultaneous
      delivery of phase-shifted, radiofrequency energy using a multipolar catheter is
      more effective and efficient in producing linear lesions than the traditional
      drag-and-burn technique. Using the multipolar ablative method to create linear
      lesions may be a useful technique in the treatment of patients with substrate
      mediated atrial fibrillation.

PMID- 16101636
TI  - The "short-coupled" variant of right ventricular outflow ventricular tachycardia:
      a not-so-benign form of benign ventricular tachycardia?
AB  - Idiopathic ventricular tachycardia (VT) originating from the right ventricular
      outflow tract (RVOT-VT) and idiopathic RVOT-extrasystoles are generally
      considered benign arrhythmias. We described three cases who originally presented
      with typical "benign looking" RVOT-extrasystoles or RVOT-VT but developed
      malignant polymorphic VT during follow-up. The unusual aspect of their RVOT
      extrasystoles was their coupling interval, which appears to be intermediate
      between the ultra-short coupling interval of idiopathic VF and the long coupling
      interval seen in the truly benign RVOT-VT.

PMID- 16101637
TI  - Disconnection of the left atrial appendage for elimination of foci maintaining
      atrial fibrillation.
AB  - We report a case with paroxysmal atrial fibrillation, in whom multiple foci were
      identified in the left atrial appendage after pulmonary vein isolation. The
      patient was successfully treated by catheter ablation to disconnect this
      structure.

PMID- 16101638
TI  - A wide complex tachycardia in a woman with myotonic dystrophy: what is the
      tachycardia mechanism?

PMID- 16101639
TI  - Absent left inferior pulmonary vein in a patient undergoing atrial fibrillation
      ablation.

PMID- 16101640
TI  - Interatrial conduction delay and atrioventricular block due to primary cardiac
      lymphoma.

PMID- 16101641
TI  - Genetics of right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart
      muscle disease that may result in arrhythmia, heart failure, and sudden death.
      The hallmark pathological findings are progressive myocyte loss and fibrofatty
      replacement, with a predilection for the right ventricle. However, variants of
      ARVC that preferentially affect the left ventricle are increasingly recognized.
      ARVC is distinguished from dilated cardiomyopathy by a propensity toward
      ventricular arrhythmia and sudden death in the absence of significant ventricular
      dysfunction. In the majority of families, ARVC shows autosomal dominant
      inheritance with incomplete penetrance. Recessive forms are also described, often
      in association with cutaneous disorders. Causative mutations have so far been
      identified in plakoglobin, desmoplakin, and plakophilin, all of which encode key
      components of the desmosome. Desmosomes are protein complexes that anchor
      intermediate filaments to the cytoplasmic membrane in adjoining cells, thereby
      forming a three-dimensional scaffolding that provides tissues with mechanical
      strength. Unraveling of the genetic etiology of ARVC has elicited a new model for
      pathogenesis. Impaired functioning of cell adhesion junctions during exposure to
      shear stress may lead to myocyte detachment and death, accompanied by
      inflammation and fibrofatty repair. At least three mechanisms contribute to the
      arrhythmic substrate: bouts of myocarditis, fibrous and adipose infiltrates that
      facilitate macroreentry, and gap junction remodeling secondary to altered
      mechanical coupling. The latter may underlie arrhythmogenicity in early disease.
      Although ARVC can be considered a disease of the desmosome, a variety of other
      genetic defects give rise to phenocopies, which may ultimately enhance our
      understanding of the broad phenotypic spectrum.

PMID- 16101643
TI  - Novel imaging techniques of the esophagus enhancing safety of left atrial
      ablation.

PMID- 16101644
TI  - Overweight and obesity in Irish primary schools: retrospective cohort study.
AB  - BACKGROUND: This retrospective cohort study investigates the feasibility of using
      established methods and routinely generated data from the statutory primary
      school health-screening programme to estimate prevalence rates for childhood
      overweight and obesity in children from a rural area in the Republic of Ireland
      (ROI). METHOD: Paper-based records in the primary school health service for
      County Leitrim and parts of County Cavan in north-west of ROI were hand searched
      to identify children attending senior infant classes during academic year
      2001/2002. Electronic calculation of body mass index (BMI) and age at examination
      was carried out. Application of age- and sex-specific cut-off points from
      International Obesity Task Force (IOTF) and United Kingdom (UK) standard
      definitions for childhood overweight and obesity was used to determine age- and
      sex-specific prevalence rates for childhood overweight and obesity. RESULTS: The
      eligible cohort was almost completely identified and consisted of 361 children.
      Weight and height measurements were available on 328 (91%) children aged between
      4.22 and 7.92 years. IOTF standard application gave prevalence rates of 25% for
      obesity and overweight in boys and 26% in girls. With the UK growth standard,
      this increased to 34% in boys and reduced to 23% in girls. CONCLUSION: It is
      feasible to generate prevalence rates for childhood overweight and obesity from
      data routinely obtained through the statutory school health-screening programme
      in ROI. This study suggests levels of childhood overweight and obesity comparable
      to other Western societies. Further research on developing a universally accepted
      standard definition of childhood overweight and obesity is required.

PMID- 16101645
TI  - Using the Internet? The experiences of parents of disabled children.
AB  - BACKGROUND: Research has offered consistent evidence that the provision of
      crucial information to parents of disabled children, at a time when they need it
      and in a form that they can use, is an intractable problem. This makes it
      important to develop new and effective approaches to information presentation,
      distribution and delivery. The Internet has been put forward as a medium through
      which families' needs for information and services can be met. This paper looks
      at parents of disabled children's experience of using it. METHODS: A cross
      sectional survey of 3014 adult carers, of which 788 were carers of disabled
      children aged 0-17. Data were collected using a postal questionnaire. RESULTS: A
      high proportion (75%) had previously used the Internet. Of these, 63% were
      frequent users and 91% were using it at home. Popular uses were emailing,
      obtaining information about caring, ordering equipment and shopping online.
      Despite positive benefits, users experienced problems relating to technical
      issues and equipment and system design. Lack of time owing to caring and other
      circumstances was an issue for over half of all users. Never users were more
      likely to be living in rented accommodation, be unemployed and not have a PC at
      home. Reasons for not using the Internet included lack of access to equipment,
      cost and lack of skill. CONCLUSIONS: For some parents the Internet is a viable
      and flexible medium for accessing useful information and services. However,
      caution about the extent to which it becomes the primary means for delivering
      information is needed. Technical problems and lack of time can make it difficult
      to search for complex information. The 'digital divide' between users and non
      users makes it crucial that issues of cost, lack of equipment and skill be
      addressed. Information needs to be made available in other forms to ensure that
      those who cannot or do not wish to use the Internet are not socially excluded.

PMID- 16101646
TI  - Mothers' attitudes to the randomized controlled trial (RCT): the case of acute
      lymphoblastic leukaemia (ALL) in children.
AB  - OBJECTIVES: Survival rates for childhood cancer have improved substantially
      partly as a result of national and international randomized clinical trials
      (RCT). However, the decision for families is complex and emotional. Our aim was
      to describe the views of mothers of children newly diagnosed with ALL regarding
      consent to randomized controlled trials. DESIGN: Qualitative interview to explore
      mothers knowledge, and reasons for involving their child in RCTs. Interviews took
      place in mothers' homes. PARTICIPANTS: Fifty mothers of children with newly
      diagnosed ALL (age 4-16 years; mean = 7.4) recruited through research nurses at
      outpatient appointments. RESULTS: All but three families had consented for their
      child to be treated in the RCT, although there was wide variation in their
      understanding of the aims, costs and benefits. Most mothers reported the aim of
      the trial to compare 'old' and 'new' treatments. CONCLUSION: Despite detailed
      verbal and written information, mothers were poorly informed about the purpose of
      the trial, and possibility of side effects. Individual preferences for either
      standard or new treatment were routinely reported. The data raise questions about
      the extent to which families give truly informed consent to recruitment of their
      child to an RCT.

PMID- 16101647
TI  - Illness incidence and health seeking behaviour among street children in
      Rawalpindi and Islamabad, Pakistan - a qualitative study.
AB  - BACKGROUND: This is the first study in Pakistan to elicit street children's
      perceptions of health and the barriers to service utilization. METHODS: A
      descriptive, cross-sectional study was carried out during September and October
      2000. The data were collected in twin-cities of Rawalpindi and Islamabad through
      individual, semi-structured street-based interviews; with 40 school age
      participants; in addition, three focus group discussions were also completed. The
      sampling was convenience based. This strategy was applied because of the non
      existence of a sampling frame for the street-based children owing to the absence
      of any census or other reports, and also the difficulty of tracking very mobile
      street children. RESULTS: Results indicate that these youth were highly
      susceptible to many adverse health outcomes. The common ailments were injuries,
      respiratory and skin infections. Along with low self-perceived severity of
      medical problems, self-medication was preferred and medical pluralism existed.
      Their perceived constraints to services included long waiting time, monetary,
      negative attitude of service providers and their inferior status. CONCLUSIONS: In
      developing user-friendly services, it is important to be sensitive to street
      children's needs and requirements. Eliminating these barriers and the integration
      of health services among public and private resources are imperative for the
      regular and sustainable provision of health care to this vulnerable, under-served
      group of children.

PMID- 16101648
TI  - At HOME in Scotland: validation of the home observation for measurement of the
      environment inventory.
AB  - BACKGROUND: This study used the Home Observation for Measurement of the
      Environment (HOME) Inventory to measure aspects of the quality and quantity of
      psychological stimulation and cognitive support available in the home environment
      of a sample of Scottish children and to examine the effectiveness of this measure
      in a British context. METHODS: Forty-seven families who had previously attended
      parent-training programmes at family centres were assessed. The Middle Childhood
      (MC) and Early Adolescent (EA) version of the HOME were used with children aged
      between 8 and 13 years old. Measures of family adversity were also taken.
      RESULTS: There were no significant differences in the demographics of the MC-HOME
      and EA-HOME groups nor in their total HOME scores. Total HOME scores were
      compared with independent measures of family adversity. The results of the MC
      HOME and the EA-HOME were similar to results reported for socially deprived
      American samples. DISCUSSION: This Scottish sample had similar MC-HOME and EA
      HOME scores as previously reported in American samples and the HOME scores
      related strongly to family adversity, supplying a proximal link between social
      conditions and the environment of children. These results suggest that the HOME
      Inventory is reliable and has concurrent validity with measures of social
      adversity in a British sample.

PMID- 16101649
TI  - The Tayside children's sleep questionnaire: a simple tool to evaluate sleep
      problems in young children.
AB  - BACKGROUND: Behavioural sleep problems in young children are relatively common
      with between 20% and 40% of those aged 1 to 5 years being affected. This paper
      describes the development of a simple questionnaire to assess disorders of
      initiating and maintaining sleep (DIMS) in children aged between 1 and 5 years
      for use as a selection tool for research purposes or as a screening instrument in
      primary care. METHODS: A subsection of the Sleep Disturbance Scale for Children
      was adapted and piloted with a small sample of children in two inner city GP
      practices (n = 81). Face and content validity were initially established by
      expert review. Discriminant validity was assessed qualitatively using interviews
      with mothers of identified cases and non-cases. The validity of the cut-off score
      was assessed by blinded case note reviews off known cases; inter-rater
      reliability was also calculated. Following modifications, the final questionnaire
      was posted to a representative sample of parents across the region with children
      in the appropriate age band (n = 1023). Internal reliability was assessed using
      Cronbach's alpha and factor analysis was undertaken to identify significant
      factors within the questionnaire. RESULTS: The response rate to the population
      questionnaire was 61.5% (n = 628) with 218 of the children having sleep scores
      that were indicative of DIMS (35%), echoing other figures reported in the
      literature. There was good internal consistency for the items (Cronbach's alpha =
      0.85) with two main factors accounting for 58% of the variance. CONCLUSION: The
      Tayside Children's Sleep Questionnaire (TCSQ) is an easy-to-read and reliable
      tool that could be used both as a clinical and research instrument to assess the
      severity and prevalence of DIMS in young children.

PMID- 16101650
TI  - Low-income Canadian Aboriginal and non-Aboriginal parent-child interactions.
AB  - BACKGROUND: Limited research is available on the performance of North American
      Aboriginal(1) people on the Nursing Child Assessment Teaching Scales (NCATS) and
      available research examines parent-child interactions within Aboriginal samples
      drawn from the USA. Most published normative data on low-income people's
      performance on the NCATS are also limited to samples drawn from the USA. The
      purpose of this research study was to use the NCATS measure to: (1) begin to
      develop a knowledge base that describes the parent-child interactions observed in
      Canadian low-income samples; and (2) explore the relationship between parent
      infant interactions and ethnicity (Aboriginal or Non-Aboriginal) within a low
      income Canadian sample. METHODS: Secondary analysis was completed on data
      collected as part of a larger study designed to examine the impact of low-income
      situations on pre-school children's health and development in Edmonton, Alberta,
      Canada. The NCATS measure of parent-child interaction was administered to all
      children (1-36 months old) and their parents in the low-income non-probability
      sample. The sample derived for secondary analysis consists of 12 Aboriginal
      parent-child pairs (11 mothers and 1 father) and 48 Non-Aboriginal parent-child
      pairs (47 mothers and 1 father). RESULTS: The data analysis suggests that
      although low-income Aboriginal parents may be less verbal with their children in
      interactions, the overall interaction quality is not different from that of other
      low-income parents. However, both groups' parent-child interaction scores were
      less than the published 10th percentile cut-off score, indicating 'worrisome
      scores' and less than optimal interactions. CONCLUSION: While the findings that
      compare the Aboriginal and Non-Aboriginal samples are limited by the small sample
      size, the fact that these findings agree with those from heterogeneous Aboriginal
      samples drawn from the USA are encouraging. Finally, the findings provide needed
      information about parent-child interactions in Canadian low-income urban samples
      including data from Aboriginal parents and children.

PMID- 16101651
TI  - A prospective cohort study comparing hospital admission for gastro-enteritis with
      home management.
AB  - OBJECTIVES: To compare physical and psychological outcomes in children presenting
      at Accident and Emergency Departments (A&E), diagnosed with gastro-enteritis and
      admitted to hospital with those of a similar age, sex and severity of illness
      discharged home. The physical and psychological well-being of children in these
      two groups, in the month after the episode, were compared as was further use of
      health care services. DESIGN: A prospective cohort study. METHODS: A comparison
      of 116 children aged 1-6 years with gastro-enteritis, presenting at A&E over a 6
      months period. Admitted children were compared with children discharged, of a
      similar age, sex and illness severity (triage score) with follow-up at 1 week and
      1 month. Clinical history, psychosocial factors, investigations and outcomes were
      recorded at presentation and physical, psychological and family outcomes at 1
      week and 1 month. RESULTS: Of 116 children, 112 (97%) completed the study (56 in
      each group). No differences were detected in psychosocial factors, socio-economic
      status, family factors, time of arrival at A&E or waiting times. Parental
      perception of illness was greater in the admitted group (P < 0.005), but was
      recorded after the decision on admission was made. At 1 week follow-up admitted
      children had increased separation anxiety compared with children who were
      discharged (P < 0.05), but this difference disappeared at 1 month. Clinical
      outcomes were the same for both groups, although admitted children had more
      investigations (91% vs. 39%). Parents were equally satisfied with their child's
      treatment, but one-third of children in both groups sought further consultation
      with a health professional in the following week. CONCLUSIONS: There is no
      statistically significant difference in socio-demographic data, time of arrival
      at A&E, waiting times, clinical and psychosocial outcomes in children with acute
      gastro-enteritis admitted to hospital compared with a group of children of
      similar age, gender and severity of illness managed at home. However, parents
      seek reassurance and follow-up of acutely ill children, even if the child is
      admitted to hospital, which has service and resource implications.

PMID- 16101652
TI  - Identifying psychosocial problems among youth: factors associated with youth
      agreement on a positive parent-completed PSC-17.
AB  - BACKGROUND: The choice of informant is a critical piece in the identification of
      psychosocial problems in youth. While many behavioural measures have been adapted
      to include information from multiple sources, in the case of parents and youth,
      poor agreement has been found. Our study purpose was to identify youth and parent
      factors associated with whether the youth agrees with a positive parent-completed
      screen of youth psychosocial problems. METHODS: Parents of youth aged 10-15 years
      who were seen for a medical visit at eight clinics completed the 17-item
      Pediatric Symptom Checklist (PSC-17). Youth scoring positive on the screen and
      their parents/guardians were interviewed by telephone after the visit (n = 145).
      We conducted bivariate and multivariate analyses to identify parent
      characteristics and child factors associated with whether the youth agrees with
      the positive parent-completed screen. RESULTS: Fifty per cent of youth
      participants agreed with their parent on a positive parent-completed PSC-17 based
      on their completion of the Y-PSC-17 as a self-report measure. Youth who reported
      a positive Y-PSC-17 in agreement with their parent were twice as likely to meet
      diagnostic cut-offs on sub-scales of anxiety/depression and aggression on the
      Child Behaviour Checklist (P < 0.01 and P < 0.05 respectively), reported lower
      parent-child connectedness (P < 0.01) and their parents reported more
      anger/frustration (P < 0.05) than youth who disagreed with the positive parent
      completed screen. Most of these associations remained significant when
      controlling for the other factors and demographic characteristics in multivariate
      analysis. CONCLUSIONS: Findings indicate that when the youth agrees with a
      positive parent-completed PSC-17, there is higher parent frustration, lower
      parent-child connectedness, and the youth is more likely to have a diagnosis of
      an emotional or behavioural disorder. Thus, when possible, the use of both parent
      and youth as informants provides necessary information in formulating a
      comprehensive treatment strategy to address the psychosocial needs of youth.

PMID- 16101653
TI  - An analysis of the factors influencing the paediatrician-parents relationship:
      the importance of the socio-demographic characteristics of the mothers.
AB  - BACKGROUND: The paediatrician-parents meeting is not always characterized by
      mutual understanding and final satisfaction. Anxiety and preconceptions of the
      parents and clinicians may have consequences for the formulation of the
      diagnosis, for the pharmacological prescription, for the therapeutic alliance.
      METHODS: We performed a survey in collaboration with a representative sample of
      Italian paediatricians and mothers in the Veneto region to investigate the
      influence of paediatricians' and families' socio-demographic characteristics on
      some clinical aspects of the visit and on their relationship. The survey
      consisted of a first 7-item anonymous questionnaire addressed to paediatricians
      and to mothers. An univariate analysis (Pearson chi(2)-test) was applied.
      RESULTS: A total of 276/527 family paediatricians and 2567/5270 mothers completed
      the questionnaire. The 69.7% of responding paediatricians reported that mothers
      are very anxious during the visit and require a therapy (especially antibiotics).
      However, only 9.74% of mothers said they required a therapy, mainly the younger
      mothers with a lower level of education. The mothers reported that they were
      satisfied with the time devoted and the explanations given by paediatrician. The
      main information sources for mothers are personal experience or health care
      providers' advice, with a marginal role for mass-media, mentioned especially by
      the younger, with a lower level of education and less experienced mothers.
      CONCLUSIONS: Our experience suggests that maternal anxiety and physicians'
      interpretation of parental expectations are important factors to take into
      account during the visit. The paediatricians are not always good predictors of
      parental expectations. Younger mothers, with a lower level of education and with
      less experience need more time, more information and support by paediatricians.
      They are more likely to request therapy, are less satisfied, more easily
      influenced and likely to follow mass-media advice, rather than a reliable source
      of information.

PMID- 16101654
TI  - Participation of disadvantaged parents in child care research.
AB  - AIM: To assess the level to which parents from deprived and socially
      dysfunctional families collaborate in complex and time-consuming research.
      DESIGN: Home-based study, of early physiological development in infants from a
      severely deprived area. Overnight continuous recordings of deep-body temperature
      with twice daily urine collection, parental daily diary of life-events and
      completion of child care social and psychological assessment by interview
      questionnaire. Measurements taken between age 6-12 weeks, each lasted 8-12 h per
      night, averaging four nights per baby. Level of parental participation assessed
      in relation to ongoing lifestyle pressures. Setting Home based. Inner city
      deprived estate. PARTICIPANTS: Random sample of mothers with newborn healthy
      infants. MEASUREMENTS: A total of 87 overnight deep body temperature recordings
      were made on 22 infants each lasting 8-12 h; 174 urine samples were taken; and 22
      sets of questionnaires were completed. RESULTS: Of 62 inner city deprived
      parents, 39 (62%) agreed to participate. 22 (35%) completed the study. Ongoing
      lifestyle pressures were high including incidents of burglary, fire and family
      violence. Family and partner pressures and life crises overwhelmed 10 non
      participations. CONCLUSIONS: Research partnerships can be developed with
      underprivileged families facing severe life-events. Parents were highly motivated
      to complete what they perceived as important infant care research.

PMID- 16101655
TI  - Influence of family environment on language outcomes in children with
      myelomeningocele.
AB  - BACKGROUND: Previously, our studies demonstrated language differences impacting
      academic performance among children with myelomeningocele and shunted
      hydrocephalus (MMSH). This follow-up study considers the environmental
      facilitators within families (achievement orientation, intellectual-cultural
      orientation, active recreational orientation, independence) among a cohort of
      children with MMSH and their relationship to language performance. METHODS: Fifty
      eight monolingual, English-speaking children (36 females; mean age: 10.1 years;
      age range: 7-16 years) with MMSH were evaluated. Exclusionary criteria were prior
      shunt infection; seizure or shunt malfunction within the previous 3 months;
      uncorrected visual or auditory impairments; prior diagnoses of mental retardation
      or attention deficit disorder. The Comprehensive Assessment of Spoken Language
      (CASL) and the Wechsler Abbreviated Scale of Intelligence (WASI) were
      administered individually to all participants. The CASL Measures four subsystems:
      lexical, syntactic, supralinguistic and pragmatic. Parents completed the Family
      Environment Scale (FES) questionnaire and provided background demographic
      information. Spearman correlation analyses and partial correlation analyses were
      performed. RESULTS: Mean intelligence scores for the MMSH group: full scale IQ
      92.2 (SD = 11.9). The CASL revealed statistically significant difficulty for
      supralinguistic and pragmatic (or social) language tasks. FES scores fell within
      the average range for the group. Spearman correlation and partial correlation
      analyses revealed statistically significant positive relationships for the FES
      'intellectual-cultural orientation' variable and performance within the four
      language subsystems. Socio-economic status (SES) characteristics were analyzed
      and did not discriminate language performance when the intellectual-cultural
      orientation factor was taken into account. CONCLUSION: The role of family
      facilitators on language skills in children with MMSH has not previously been
      described. The relationship between language performance and the families' value
      on intellectual/cultural activities seems both statistically and intuitively
      sound. Focused interest in the integration of family values and practices should
      assist developmental specialists in supporting families and children within their
      most natural environment.

PMID- 16101656
TI  - Comparison of a dedicated children's seizure clinic to mixed general paediatric
      clinics.
AB  - BACKGROUND: In the light of recent recommendations regarding the current
      management of children with possible epilepsy in the UK, different models of care
      are compared using an existing validated audit tool. METHODS: The initial
      clinical assessment process, investigation, management and communication
      regarding children referred with suspected epilepsy to general paediatric clinics
      or a paediatric seizure clinic was compared using the British Paediatric
      Neurology Association (BPNA) audit tool. Results Ninety-three children were
      included in the comparison. The history and description of the episodes was
      better documented in the Seizure Clinic (SC). Children's early development (79%
      vs. 50%) and school performance (86% vs. 42%) were better documented in the SC.
      Documentation of possible side effects relating to newly prescribed anti
      epileptic drugs was poor in both groups (33% vs. 15%). CONCLUSIONS: Differences
      between models of epilepsy care can be detected using audit tools although there
      are some methodological limitations of this particular study. Future similar
      studies as well as informing local practice can add to the debate on the
      appropriate way forward in improving the care for children with epilepsy.

PMID- 16101657
TI  - Rates and social patterning of household smoking and breastfeeding in contrasting
      European settings.
AB  - OBJECTIVE: To compare rates and social patterning of household smoking and
      breastfeeding in families with newborn infants in birth cohorts in Coventry, UK
      and Veria, North Greece. METHODS: Infants born in 1996 in Coventry, 1999 in Veria
      were recruited into birth cohort studies using similar methodologies. In Coventry
      recruitment was by family health visitor at the primary visit; in Veria, hospital
      based paediatricians enrolled infants at the neonatal examination. Data were
      collected at the initial contact on household smoking, type of feeding, and
      household socio-demographic characteristics. Rates of initial breastfeeding and
      household smoking with 95% confidence intervals were estimated and breastfeeding
      and household smoking regressed on parental education and housing tenure in
      logistic regression models. RESULTS: Data were available on 2612 Coventry infants
      and 773 Veria infants. Rates of household smoking and breastfeeding were higher
      in Veria compared to Coventry. In Coventry, living in rented accommodation and
      lower maternal and paternal education were associated with household smoking and
      bottle feeding. Logistic regression models fitted on initiation of breastfeeding
      failed to show social patterning in Veria but more educated mothers showed a
      longer duration of breastfeeding. Only low paternal education was associated with
      household smoking after adjustment for maternal education and housing tenure.
      CONCLUSIONS: Smoking and breastfeeding are more prevalent among households with
      young infants in Veria compared with Coventry. The social patterning of health
      related behaviours noted in Coventry is less marked in Veria. The relevance of
      these findings for public health interventions in the contrasting settings is
      discussed.

PMID- 16101658
TI  - Drowning of British children abroad.
AB  - AIMS: To quantify the risks of British children drowning abroad. METHODS: The
      numbers of British children drowning abroad were estimated for 1996-2003 using
      the RoSPA/RLSS press cutting database. We compared these figures with the numbers
      of British children going abroad from the International Passenger Survey from the
      Office of National Statistics. RESULTS: Sixty-eight children (45 boys-23 Girls)
      drowned in the eight-year period: 48 (71%) in swimming pools (mostly in hotels).
      Allowing for exposure, the rate was higher in North America [5.2 (CI 2.9
      9.4)/million tourists] than the European Union [1.9 (CI 1.4-2.5)/million
      tourists] p = 0.002. DISCUSSION: On average eight British children drown each
      year abroad. This is therefore a rare but tragic event. Most of these episodes
      happen in swimming pools and this needs to be compared to the one child that dies
      each year in municipal swimming pools in the United Kingdom where there is
      adequate lifeguarding. It may be that parents have a false sense of security for
      their children in pools abroad. We believe that there needs to be action from the
      European Union on this important event.

PMID- 16101659
TI  - Young gymnasts' understanding of sport-related pain: a contribution to prevention
      of injury.
AB  - INTRODUCTION: Pain may signal impending or actual injury, or the achievement of
      optimum workload to produce a physical conditioning effect. These different
      functions of pain present a challenge for athletes wanting to improve their skill
      and conditioning level in the most efficient manner without injury. As children
      may be particularly vulnerable to exacerbating pain and injury owing to limited
      knowledge, it is important to learn more about the development of their
      understanding of pain concepts (e.g. pain as a signal of impending injury vs.
      soreness from exertion). METHODS: A structured interview and scoring criteria
      were developed to measure children's understanding of the functions of pain in
      sport and the consequences of pain and injury. Competitive gymnasts (6-13 years;
      n = 68; 63% girls) were interviewed and their responses were scored for indices
      of understanding of different types of pain. RESULTS: Age differences were found
      in: number of different types of pain identified; understanding of pain
      causality; understanding the value of pain; distinguishing pain from exertion;
      and use of pain descriptors. Analyses revealed that gymnasts responded
      differently to different types of pain and were aware of the need to stop their
      sport in some cases and to continue in others. Most did not describe social
      pressure to continue gymnastics while in pain. Gymnasts demonstrated an
      understanding that there was little they could do about chronic pain, yet
      appreciated that pain or damage could worsen with continued practice. DISCUSSION:
      This study was a first step in elucidating young gymnasts' understanding of sport
      related pain. Further research is needed with athletes from other sports, and
      comparisons should be made with non-athletic children and those with pain from
      other sources. Within various sports, it will be important to determine the
      relative effects of age, sex, and number of hours spent training. Appreciation of
      individual differences in children's understanding of pain may contribute to
      prevention of injury in sport. For example, children who understand the
      difference between soreness from exertion and acute pain owing to injury may be
      able to make better decisions about pain management and continued practice.

PMID- 16101660
TI  - Is the personal child health record used in secondary care?
AB  - BACKGROUND: Hampshire et al. (2004) have recently reported on the variation in
      use of the Personal Child Health Record (PCHR) (The Red Book). This study aims to
      add further data to the discussion. OBJECTIVE: To estimate the proportion of
      parents bringing the Red Book to a hospital surgical outpatient appointment.
      METHODS: An audit was performed over 4 months ending 14 July 2004. This involved
      the author noting whether parents brought the Red Book to the Paediatric Plastic
      and Reconstructive Surgery clinics, on different sites and including specialist
      multidisciplinary clinics. 200 consecutive attendees were reviewed.

PMID- 16101665
TI  - Is there a rationale for therapeutic immunoadsorption in multiple sclerosis?

PMID- 16101666
TI  - Developments in the inhibition of gastric acid secretion.
AB  - Understanding the physiology of gastric acid secretion and the pathophysiology of
      acid-related diseases (e.g. gastrooesophageal reflux and peptic ulcer) has led to
      the development of numerous ways to decrease acid exposure. Pharmacologically one
      can try to neutralize secreted acid by antacids, prevent stimulation of the
      parietal cell, improve mucosal defences and block the functioning of the proton
      pump. Proton pump inhibitors (PPIs) inhibit the final step of acid secretion, and
      are currently the most potent acid inhibitors. Major therapeutic improvement
      within the PPI class appears unlikely, as agents in this class share similar
      chemistry, mode of action, and pharmacokinetic profiles. New approaches that
      block acid secretion are now being developed. Gastrin (CCK2) receptor antagonists
      and potassium-competitive acid blockers (P-CABs) are in clinical development.

PMID- 16101667
TI  - Not all statins interfere with clopidogrel during antiplatelet therapy.
AB  - BACKGROUND: Clopidogrel and statins are frequently coadministered in patients
      with ischemic heart diseases. Recent reports suggested that clopidogrel's
      effectiveness in inhibiting adenosine diphosphate (ADP)-induced platelets
      aggregation is attenuated by co-administration of certain statins. The objective
      of the present study was to define which statin might interfere with the
      antiaggregation property of clopidogrel. METHODS: We designed a pharmacokinetic
      study and tested ex vivo platelet function on 21 healthy volunteers who received
      clopidogrel and all currently commercially available statins: rosuvastatin [10 mg
      o.d.], simvastatin [20 mg o.d.], fluvastatin [80 mg o.d.], pravastatin [40 mg
      o.d.], and atorvastatin [20 mg o.d.]. Each statin was administered for 7 days
      followed by 1 week of wash-out period with clopidogrel treatment alone. Detection
      of the statins in the plasma was performed on all blood samples, using HPLC
      analytical method. RESULTS: All individuals, except one, were responders to
      clopidogrel with inhibition of ex vivo ADP induced platelet aggregation. All
      statins, except pravastatin, were detectable in the plasma at the end of each
      treatment period in all patients, and no statin was detectable after any of the
      wash-out periods. Clopidogrel was significantly less efficient to prevent
      platelet aggregation when coadministrated with simvastatin or fluvastatin. No
      difference was observed in clopidogrel efficacy when coadministered with
      rosuvastatin, pravastatin or atorvastatin. CONCLUSIONS: This is the first study
      investigating clopidogrel-statin interactions on ex vivo platelet function with
      all commercially available statins and which were administered to the same
      individuals. It demonstrates in healthy volunteers that at the doses used in this
      study, simvastatin and fluvastatin, but not atorvastatin, pravastatin or
      rosuvastatin interfere with the anti-aggregation effect of clopidogrel.

PMID- 16101668
TI  - Lipid metabolism and TNF-alpha secretion in response to dietary sterols in human
      monocyte derived macrophages.
AB  - BACKGROUND: The postprandial phase is characterized by the circulation of
      atherogenic dietary-triacylglycerol rich lipoproteins. Little is known about the
      modulation of lipid and immune functions in macrophages by these particles or of
      the role of the oxysterols found in food such as 7beta-hydroxycholesterol and 7
      ketocholesterol. MATERIALS AND METHODS: Human macrophages were tested with
      different concentrations of chylomicron remnant-like particles (CRLP) with or
      without incorporated oxysterols to study their uptake by the cells, and their
      effects on cholesteryl ester and triacylglycerol synthesis and the secretion of
      inflammatory mediators, including tumour necrosis factor-alpha (TNF-alpha),
      interleukin 6 (IL-6) and interleukin 10 (IL-10). RESULTS: Independently of the
      presence of oxysterols, CRLP caused cholesterol accumulation. However, the dose
      dependent increase in [3H]cholesterol internalization by macrophages after
      incubation with [3H]cholesteryl ester-labelled CRLP was abolished by the presence
      of oxysterols in the particles. TNF-alpha secretion was decreased and that of IL
      10 unaffected by CRLP independently of the presence of oxysterol. Exposure to
      CRLP containing 7beta-hydroxysterol, but not to CRLP or 7-ketosterol-containing
      CRLP, reduced IL-6 secretion with respect to cells not exposed to any particles.
      Because TNF-alpha levels have been related to scavenger receptor expression, we
      tested the uptake of modified LDL in macrophages exposed to human postprandial
      triacylglycerol-rich lipoproteins and found it to be markedly increased.
      CONCLUSIONS: Cholesterol loading as a result of dietary lipids depresses the
      inflammatory response of macrophages and the presence of 7beta-hydroxysterol may
      exacerbate this effect. In addition, exposure to dietary lipids enhances
      scavenger receptor activity in macrophages. These results suggest that changes
      induced by dietary lipids in human macrophage function are related to an
      increased propensity of the cells to accumulate lipids during the postprandial
      phase.

PMID- 16101669
TI  - Is the intensity of the highest fat oxidation at the lactate concentration of 2
      mmol L(-1)? A comparison of two different exercise protocols.
AB  - BACKGROUND: The exercise intensity eliciting highest fat oxidation is important
      for a variety of populations and its precise determination requires an adequate
      exercise protocol. The aim of this study was to compare fat oxidation,
      concentration of lactate and lactate threshold during an established exercise
      protocol using fixed workloads with a protocol based upon the subject's
      individual heart rate response to exercise. MATERIALS AND METHODS: Highest fat
      oxidation, concentration of lactate and lactate threshold were compared between
      two different exercise protocols in moderately trained men (n = 48) and women (n
      = 30). In randomized order subjects completed a standardized (STAND) and an
      individual (IND) submaximal exercise test. The increments during IND were adapted
      by the subjects' individual heart rate response to exercise compared to STAND
      with defined steps. RESULTS: In men, fat oxidation was significantly higher at
      the intensity eliciting highest fat oxidation in STAND than in IND (P = 0.019),
      but not in women. In both genders lactate concentration (P < 0.001) and heart
      rate (HR) (P < 0.001) were significantly higher in IND compared to STAND at this
      intensity. A significant correlation between O2 at lactate threshold and the
      intensity eliciting the highest fat oxidation was found in both genders in IND
      (women r = 0.73; men r = 0.43) and in STAND (women r = 0.57; men r = 0.56).
      CONCLUSION: Different exercise increments and stage durations have an influence
      on lactate concentration and HR at the intensity eliciting the highest fat
      oxidation. The shorter test duration of STAND favours this protocol to determine
      maximal fat oxidation. For the untrained, start of exercise should be at very low
      intensity.

PMID- 16101670
TI  - Blood profiles, body fat and mood state in healthy subjects on different diets
      supplemented with Omega-3 polyunsaturated fatty acids.
AB  - BACKGROUND: Diets and Omega-3 polyunsaturated fatty acids have been considered as
      important factors to reduce the risk of cardiovascular and inflammatory diseases,
      but there are few details on the effects on healthy subjects. The aim of the
      present study was to examine the variation of several physiological parameters in
      healthy subjects on different diets supplemented with Omega-3 fatty acids.
      MATERIALS AND METHODS: The experiment was carried out on 33 subjects divided into
      four groups according to a double-blind cross-over design with a 1 : 1 ratio for
      Omega-3 (vs. placebo) and open-label parallel-groups with a 1 : 1 ratio for the
      Zone diet (vs. the diet suggested by the Italian National Research Institute for
      Nutrition and Foods). Blood samples were collected at the beginning of the
      experiment and after 35 (cross-over) and 70 days. The Profile of Mood States test
      (POMS) was also performed. RESULTS: The arachidonic acid/eicosapentaenoic acid
      ratio (AA/EPA) was strongly reduced by Omega-3 with a supplementary effect of the
      diet and in particular the Zone diet. The AA/EPA reduction was correlated with a
      concomitant decrease of insulin and homocysteine levels. The Zone diet reduced
      skinfold thickness and body fat percentage and also showed antioxidant effects.
      The mood state changed after Omega-3 supplementation, with an increased POMS
      index. This was related to a concomitant reduction of AA/EPA and was particularly
      evident in the Zone diet. CONCLUSION: AA/EPA and mood state are differently
      influenced by diet and Omega-3, body fat is particularly reduced by Zone diet,
      while blood parameters such as triglycerides/HDL ratio, insulin and homocysteine
      are related to AA/EPA variations. These findings are discussed in terms of
      differences in the composition of the diets and the influences of Omega-3 on
      physiological functions.

PMID- 16101671
TI  - Statin-induced blockade of prenylation alters nucleocytoplasmic shuttling of GTP
      binding proteins gamma2 and beta2 and enhances their suppressive effect on
      glucocorticoid receptor transcriptional activity.
AB  - BACKGROUND: We previously reported that the guanine tri-phosphate-binding
      proteins (G) beta and gamma are both localized in the nucleus, in addition to
      their expected cytoplasmic/plasma membrane localization. These proteins, as a
      heterodimeric complex, suppress glucocorticoid response element-mediated
      transcriptional activity of the glucocorticoid receptor through direct physical
      interactions between Gbeta and the glucocorticoid receptor. MATERIALS AND
      METHODS: As Ggamma is prenylated at a cysteine residue in its C-terminal portion,
      and as this post-translational modification is required for many of the known
      Gbeta/Ggamma activities, we examined the effect of its absence or diminution on
      Gbeta/Ggamma-induced suppression of glucocorticoid receptor-induced
      transcriptional activity. RESULTS: In a functional reporter assay, Ggamma2C68S,
      which is defective at the prenylation site, was more potent than the wild-type
      Ggamma2 at increasing Gbeta2-induced suppression of glucocorticoid receptor
      transactivation. Interestingly, the enhanced green fluorescent protein fusion of
      this mutant Ggamma2 was localized preferentially in the nucleus, while it was
      absent from the plasma membrane. Lovastatin, a 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor that abrogates the prenylation of
      Ggamma, shifted the subcellular localization of enhanced green fluorescence
      protein-fused Ggamma2 and Gbeta2 from the cytoplasm/plasma membrane to the
      nucleus and further suppressed glucocorticoid receptor-induced transcriptional
      activity. CONCLUSIONS: These findings indicate that not only is the natural
      covalent addition of the prenyl residue to Ggamma unnecessary for the
      transcriptional suppression induced by Gbeta/Ggamma on the glucocorticoid
      receptor, but rather helps retain the Gbeta/Ggamma complex away from the nucleus
      decreasing its antiglucocorticoid actions.

PMID- 16101672
TI  - Gallbladder Na+/H+ exchange activity is up-regulated prior to cholesterol crystal
      formation.
AB  - BACKGROUND: Gallbladder Na+ and H2O absorption are increased prior to gallstone
      formation and may promote cholesterol nucleation. Na+/H+ exchange (NHE) isoforms
      NHE2 and NHE3 are involved in gallbladder Na+ transport in prairie dogs. We
      examined whether increased gallbladder Na+ absorption observed during early
      gallstone formation is the result of NHE up-regulation. MATERIALS AND METHODS:
      Native gallbladder and primary cultures of gallbladder epithelial cells (GBECs)
      harvested from prairie dogs fed nonlithogenic (CON) or 1.2% cholesterol diet for
      varying lengths of time to induce cholesterol-saturated bile (PreCRYS),
      cholesterol crystals (CRYS), or gallstones (GS) were used. NHE activity was
      assessed by measuring dimethylamiloride-inhibitable 22Na+ uptake under H+
      gradient in primary GBECs. HOE-694 was used to determine NHE2 and NHE3
      contributions. NHE protein and mRNA expression were examined by Western and
      Northern blots, respectively. RESULTS: Gallbladder total NHE activity was 25.1 +/
      1.3 nmol mg protein(-1) min(-1) in the control and increased during gallstone
      formation peaking at the PreCRYS stage (98.4 +/- 3.9 nmol mg protein(-1) min(
      1)). There was a shift in NHE activity from NHE2 to NHE3 as the animals
      progressed from no stones through the PreCRYS and CRYS stages to gallstones. The
      increase in NHE activity was partly caused by an increased Vmax without any
      change in K(Na)m. Both NHE2 and NHE3 protein increased moderately during the
      PreCRYS stage without increases in mRNA expression. CONCLUSIONS: Increased
      gallbladder Na+ absorption observed prior to crystal formation is in part caused
      by an increase NHE activity which is not fully accounted for by an increase in
      NHE proteins and mRNA levels but may be explained by enhanced localization in the
      membranes and/or altered regulation of NHE.

PMID- 16101673
TI  - Immunoadsorption patients with multiple sclerosis: an open-label pilot study.
AB  - BACKGROUND: Immunoadsorption (IA) is occasionally applied in patients with acute
      relapses of multiple sclerosis (MS). This pilot study was undertaken to determine
      whether IA might help in secondary progressive and relapsing-remitting multiple
      sclerosis. DESIGN: IA was performed at 1-week intervals in 12 patients with
      secondary progressive or relapsing-remitting MS. These patients had an extended
      disability status scale (EDSS) score of 4.5-7 and an EDSS increase of 0.5 within
      6 months before inclusion in the study despite conventional drug therapy. The
      change in the EDSS and that in the MS functional composite (MSFC) score, which
      consisted of quantitative tests of arm function, ambulation, visual acuity and
      cognition, served as the primary outcome variables, which were measured at
      baseline and at 3, 6 and 12 months. Changes in quality of life and cerebral
      lesions by magnetic resonance imaging (MRI) were also assessed at baseline and
      after the last immunoadsorption (month 3). RESULTS: A significant reduction of
      the median EDSS change was observed after the treatment period, which reversed 3
      months after the immunoadsorptions had been stopped. Ten of 12 patients remained
      stable during the first year of follow-up with no significant changes of the MSFC
      scores. No significant changes in magnetic resonance imaging T2-hyperintense
      brain lesions or in the number of gadolinium-positive lesions and in the
      patients' quality of life were observed. Western blot analyses demonstrated a
      reduction of serum myelin-specific antibodies, which were collected in the
      adsorber eluates. CONCLUSIONS: Removal of immunoglobulins, including myelin
      specific antibodies by immunoadsorption, seems to delay disease progression as
      defined by EDSS, MSFC and MRI, while the patients' quality of life did not
      deteriorate.

PMID- 16101674
TI  - Association of furunculosis and familial deficiency of mannose-binding lectin.
AB  - BACKGROUND: Polymorphisms in the mannose-binding lectin gene reduce serum mannose
      binding lectin levels and are associated with enhanced risk of infection. In a
      family with recurrent staphylococcal disease presenting as furunculosis or
      carbuncles, an association with mannose-binding lectin deficiency was
      investigated. MATERIALS AND METHODS: Levels of functional mannose-binding lectin
      were estimated and the genotypes of the mannose-binding lectin gene were analysed
      on blood samples, collected from the members of one particular family with a high
      prevalence of furunculosis. RESULTS: Functional mannose-binding lectin levels in
      sera of 13 of the 28 members of one family showed deficiency. Furunculosis or
      carbuncles appeared to be present in nine of the 28 family members, seven of
      which showing the pBly allele and mannose-binding lectin deficiency. Four young
      family members of the second generation were pBly positive and mannose-binding
      lectin deficient, but had not shown furunculosis yet. CONCLUSION: Members of a
      particular family suffering from furunculosis differ from their 'healthy'
      relatives as to mannose-binding lectin genotypes, indicating the relevance of
      normal mannose-binding lectin levels in the defence against staphylococcal
      disease.

PMID- 16101675
TI  - Structure and function of the Lowe syndrome protein OCRL1.
AB  - Oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder with the
      hallmark features of congenital cataracts, mental retardation and Fanconi
      syndrome of the kidney proximal tubules. OCRL was first described in 1952, and
      exactly four decades later, the gene responsible was identified and found to
      encode a protein highly homologous to inositol polyphosphate 5-phosphatase. This
      suggested that Lowe syndrome may represent an inborn error of inositol phosphate
      metabolism, and subsequent studies confirmed that such metabolism is indeed
      perturbed in Lowe syndrome cells. However, the mechanism by which loss of
      function of the OCRL1 protein brings about Lowe syndrome remains ill defined. In
      this review, I will discuss our understanding of OCRL1, including where it is
      localized, what it interacts with and what its possible functions might be. I
      will then discuss possible mechanisms by which loss of OCRL1 may bring about
      cellular defects that manifest themselves in the pathology of Lowe syndrome.

PMID- 16101676
TI  - Caveolae: stable membrane domains with a potential for internalization.
AB  - The role of caveolae in endocytosis is hotly debated. Here, we argue that most
      caveolae are stable microdomains at the cell surface. Only a small fraction of
      caveolae is constitutively internalized, leading to a quantitatively minor uptake
      of ligands and receptors. In addition, we suggest that a more pronounced
      downregulation of caveolae from the plasma membrane can occur, presumably
      stimulated by receptor cross-linking and clustering in caveolae. Finally, we
      propose that future studies dealing with internalization of caveolae should
      actually document such internalization and include kinetic data.

PMID- 16101677
TI  - Flotillins and the PHB domain protein family: rafts, worms and anaesthetics.
AB  - While our understanding of lipid microdomains has advanced in recent years, many
      aspects of their formation and dynamics are still unclear. In particular, the
      molecular determinants that facilitate the partitioning of integral membrane
      proteins into lipid raft domains are yet to be clarified. This review focuses on
      a family of raft-associated integral membrane proteins, termed flotillins, which
      belongs to a larger class of integral membrane proteins that carry an
      evolutionarily conserved domain called the prohibitin homology (PHB) domain. A
      number of studies now suggest that eucaryotic proteins carrying this domain have
      affinity for lipid raft domains. The PHB domain is carried by a diverse array of
      proteins including stomatin, podocin, the archetypal PHB protein, prohibitin,
      lower eucaryotic proteins such as the Dictyostelium discoideum proteins vacuolin
      A and vacuolin B and the Caenorhabditis elegans proteins unc-1, unc-24 and mec-2.
      The presence of this domain in some procaryotic proteins suggests that the PHB
      domain may constitute a primordial lipid recognition motif. Recent work has
      provided new insights into the trafficking and targeting of flotillin and other
      PHB domain proteins. While the function of this large family of proteins remains
      unclear, studies of the C. elegans PHB proteins suggest possible links to a class
      of volatile anaesthetics raising the possibility that these lipophilic agents
      could influence lipid raft domains. This review will discuss recent insights into
      the cell biology of flotillins and the large family of evolutionarily conserved
      PHB domain proteins.

PMID- 16101678
TI  - HIV-1 Gag-RNA interaction occurs at a perinuclear/centrosomal site; analysis by
      confocal microscopy and FRET.
AB  - The Gag polyprotein is the major structural protein of human immunodeficiency
      virus-1 (HIV-1) constituting the viral core. Between translation on cytoplasmic
      polysomes and assembly into viral particles at the plasma membrane, it
      specifically captures the RNA genome of the virus through binding RNA structural
      motifs (packaging signals -Psi) in the RNA. RNA is believed to be a structural
      facilitator of Gag assembly. Using a combined approach of immunofluorescence
      detection of Gag protein and in situ hybridisation detection of viral genomic
      RNA, we demonstrate that Gag protein colocalises early after expression with Psi+
      RNA in the perinuclear region and also colocalises with centrioles. Colocalised
      RNA and protein subsequently traffic through the cytoplasm to the plasma membrane
      of the cell. Gag expressed from Psi- RNA diffuses throughout the cell. It is not
      found at centrioles and shows delayed cytoplasmic colocalisation with the RNA
      genome. RNA capture through Psi does not influence binding of Gag to
      microfilaments. Gag does not bind to tubulin during export. The presence of the
      packaging signal may coordinate capture of Psi+ RNA by Gag protein at the
      centrosome followed by their combined transport to the site of budding. HIV-1 Psi
      thus acts as a subcellular localisation signal as well as a high-affinity-binding
      site for Gag.

PMID- 16101679
TI  - Alpha-latrotoxin modulates the secretory machinery via receptor-mediated
      activation of protein kinase C.
AB  - The hypothesis whether alpha-latrotoxin (LTX) could directly regulate the
      secretory machinery was tested in pancreatic beta cells using combined techniques
      of membrane capacitance (Cm) measurement and Ca2+ uncaging. Employing ramp
      increase in [Ca2+]i to stimulate exocytosis, we found that LTX lowers the Ca2+
      threshold required for exocytosis without affecting the size of the readily
      releasable pool (RRP). The burst component of exocytosis in response to step-like
      [Ca2+]i increase generated by flash photolysis of caged Ca2+ was also speeded up
      by LTX treatment. LTX increased the maximum rate of exocytosis compared with
      control responses with similar postflash [Ca2+]i and shifted the Ca2+ dependence
      of the exocytotic machinery toward lower Ca2+ concentrations. LTXN4C, a LTX
      mutant which cannot form membrane pores or penetrate through the plasma membrane
      but has similar affinity for the receptors as the wild-type LTX, mimicked the
      effect of LTX. Moreover, the effects of both LTX and LTXN4C) were independent of
      intracellular or extracellular Ca2+ but required extracellular Mg2+. Our data
      propose that LTX, by binding to the membrane receptors, sensitizes the fusion
      machinery to Ca2+ and, hence, may permit release at low [Ca2+]i level. This
      sensitization is mediated by activation of protein kinase C.

PMID- 16101680
TI  - Cytoplasmic targeting of mutant poly(A)-binding protein nuclear 1 suppresses
      protein aggregation and toxicity in oculopharyngeal muscular dystrophy.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder
      characterized by progressive eyelid drooping, swallowing difficulties and
      proximal limb weakness. The autosomal dominant form of this disease is caused by
      a polyalanine expansion from 10 to 12-17 residues, located at the N-terminus of
      the poly(A)-binding protein nuclear 1 (PABPN1). A distinct pathological hallmark
      of OPMD is the presence of filamentous intranuclear aggregates in patients'
      skeletal muscle cells. Wildtype PABPN1 protein is expressed ubiquitously and was
      shown to be mostly concentrated in discrete nuclear domains called 'speckles'.
      Using an established cell- culture model, we show that most mutant PABPN1-
      positive (alanine expanded form) intranuclear aggregates are structures distinct
      from intranuclear speckles. In contrast, the promyelocytic leukaemia protein, a
      major component of nuclear bodies, strongly colocalized to intranuclear
      aggregates of mutant PABPN1. Wildtype PABPN1 can freely shuttle between the
      nucleus and cytoplasm. We determined whether the nuclear environment is necessary
      for mutant PABPN1 inclusion formation and cellular toxicity. This was achieved by
      inactivating the mutant PABPN1 nuclear localization signal and by generating full
      length mutant PABPN1 fused to a strong nuclear export sequence. A green
      fluorescence protein tag inserted at the N-terminus of both wildtype PABPN1
      (ala10) and mutant PABPN1 (ala17) proteins allowed us to visualize their
      subcellular localization. Targeting mutant PABPN1 to the cytoplasm resulted in a
      significant suppression of both intranuclear aggregates formation and cellular
      toxicity, two histological consequences of OPMD. Our results indicate that the
      nuclear localization of mutant PABPN1 is crucial to OPMD pathogenesis.

PMID- 16101681
TI  - Intercellular gamma-herpesvirus dissemination involves co-ordinated intracellular
      membrane protein transport.
AB  - The murine gamma-herpesvirus-68 (MHV-68) ORF27 encodes gp48, a type 2
      transmembrane glycoprotein that contributes to intercellular viral spread. Gp48
      is expressed on the surface of infected cells but is retained intracellularly
      after transfection. In this study, we show that the multimembrane spanning ORF58
      gene product is both necessary and sufficient for gp48 to reach the cell surface.
      ORF58-deficient MHV-68 expressed ORF27 in normal amounts, but retained it in the
      endoplasmic reticulum (ER). Transfected ORF27 also remained in ER, whereas green
      fluorescent protein-tagged ORF58 localized to the ER and trans-Golgi network.
      When ORF27 and ORF58 were co-transfected, they formed a protein complex and
      reached the cell surface. Surprisingly, ORF58 rather than ORF27 mediated cell
      binding via a small extracellular loop. The heavily glycosylated ORF27 component
      of the complex may, therefore, act mainly to protect this loop against antibody.
      The interdependent transport of ORF27 and ORF58 transport ensures that such
      protection is always present.

PMID- 16101682
TI  - Uncoupling of brefeldin a-mediated coatomer protein complex-I dissociation from
      Golgi redistribution.
AB  - The Golgi complex functions in transport of molecules from the endoplasmic
      reticulum (ER) to the plasma membrane and other distal organelles as well as in
      retrograde transport to the ER. The fungal metabolite brefeldin A (BFA) promotes
      dissociation of ADP-ribosylation-factor-1 (ARF1) and the coatomer protein complex
      I (COP-I) from Golgi membranes, followed by Golgi tubulation and fusion with the
      ER. Here we demonstrate that the cationic ionophore monensin inhibited the BFA
      mediated Golgi redistribution to the ER without interfering with ARF1 and COP-I
      dissociation. Preservation of a perinuclear Golgi despite COP-I and ARF1
      dissociation enables addressing the involvement of these proteins in anterograde
      ER to Golgi transport. The thermo-reversible folding mutant of vesicular
      stomatitis virus G protein (VSVGtsO45) was retained in the ER in the presence of
      both monensin and BFA, thus supporting ARF1/COP-I participation in ER-exit
      processes. Live-cell imaging revealed that BFA-induced Golgi tubulation persisted
      longer in the presence of monensin, suggesting that monensin inhibits tubule
      fusion with the ER. Moreover, monensin also augmented Golgi-derived tubules that
      contained the ER-Golgi-intermediate compartment marker, p58, in the absence of
      BFA, signifying the generality of this effect. Taken together, we propose that
      monensin inhibits membrane fusion processes in the presence or absence of BFA.

PMID- 16101683
TI  - The role of ARF1 and rab GTPases in polarization of the Golgi stack.
AB  - The organization and sorting of proteins within the Golgi stack to establish and
      maintain its cis to trans polarization remains an enigma. The function of Golgi
      compartments involves coat assemblages that facilitate vesicle traffic, Rab
      tether-SNAP receptor (SNARE) machineries that dictate membrane identity, as well
      as matrix components that maintain structure. We have investigated how the Golgi
      complex achieves compartmentalization in response to a key component of the coat
      complex I (COPI) coat assembly pathway, the ARF1 GTPase, in relationship to
      GTPases-regulating endoplasmic reticulum (ER) exit (Sar1) and targeting fusion
      (Rab1). Following collapse of the Golgi into the ER in response to inhibition of
      activation of ARF1 by Brefeldin A, we found that Sar1- and Rab1-dependent Golgi
      reformation took place at multiple peripheral and perinuclear ER exit sites.
      These rapidly converged into immature Golgi that appeared as onion-like
      structures composed of multiple concentrically arrayed cisternae of mixed enzyme
      composition. During clustering to the perinuclear region, Golgi enzymes were
      sorted to achieve the degree of polarization within the stack found in mature
      Golgi. Surprisingly, we found that sorting of Golgi enzymes into their
      subcompartments was insensitive to the dominant negative GTP-restricted ARF1
      mutant, a potent inhibitor of COPI coat disassembly and vesicular traffic. We
      suggest that a COPI-independent, Rab-dependent mechanism is involved in the rapid
      reorganization of resident enzymes within the Golgi stack following synchronized
      release from the ER, suggesting an important role for Rab hubs in directing Golgi
      polarization.

PMID- 16101684
TI  - ApoER2 is endocytosed by a clathrin-mediated process involving the adaptor
      protein Dab2 independent of its Rafts' association.
AB  - The apolipoprotein E receptor 2 (apoER2) is a member of the low-density
      lipoprotein receptor family which binds ligands such as reelin, apolipoprotein E
      and apolipoprotein J/clusterin and has been shown to play roles in neuronal
      migration during development and in male fertility. The function of apoER2 mainly
      depends on cellular signaling triggered by ligand binding. Although the receptor
      is internalized, the mechanism and functional significance of its endocytic
      trafficking remain unclear. Apolipoprotein E receptor 2 partitions into lipid
      rafts and interacts with caveolin-1, a feature that could modulate its endocytic
      behavior. Recent evidence also suggested that apoER2 might be endocytosed by a
      pathway independent of clathrin. Here, we show that despite a raft association,
      apoER2 internalization depends on its cytoplasmic FxNPXY motif that is similar to
      canonical motifs for clathrin-mediated endocytosis. This motif mediates receptor
      binding to the adaptor protein Dab2, which can interact directly with clathrin.
      Several inhibitory conditions of clathrin-mediated endocytosis, including
      expression of the dominant negative forms of eps15 and Dab2, decreased apoER2
      internalization. In contrast, treatment with the drug nystatin, which blocks the
      caveolar/raft internalization pathway, has no effect on the receptor's
      endocytosis. Neither the transmembrane nor the proline-rich insert of the
      cytoplasmic domain, which has been previously reported to exclude the receptor
      from the clathrin-mediated pathway, altered apoER2 endocytic activity. These
      studies indicate that apoER2 internalizes through a clathrin-mediated pathway and
      that its association with caveolar and noncaveolar rafts does not determine its
      endocytosis.

PMID- 16101685
TI  - Blood infectivity, processing and screening tests in transmissible spongiform
      encephalopathy.
AB  - Surprising advances have been made in the areas of blood infectivity, infectivity
      removal and, especially, blood screening tests for transmissible spongiform
      encephalopathy (TSE) in the past few years. In fact, if anyone as recently as
      last year had suggested that a screening test for preclinical human infection
      might be available before the end of 2005, the statement would have been met with
      smiling disbelief. Nevertheless, it can be confidently predicted that the
      diagnostic misfolded 'prion' protein (PrP(TSE)) will soon be reliably detectable
      in blood during the symptomatic phase of disease, and it is highly probable that
      it will also be detectable in blood from at least a proportion of infected
      individuals during the preclinical phase of disease.

PMID- 16101686
TI  - Evaluation of an automated high-volume extraction method for viral nucleic acids
      in comparison to a manual procedure with preceding enrichment.
AB  - BACKGROUND AND OBJECTIVES: Nucleic acid extraction still harbours the potential
      for improvements in automation and sensitivity of nucleic acid amplification
      technology (NAT) testing. This study evaluates the feasibility of a novel
      automated high-volume extraction protocol for NAT minipool testing in a blood
      bank setting. MATERIALS AND METHODS: The chemagic Viral DNA/RNA Kit special for
      automated purification of viral nucleic acids from 9.6 ml of plasma by using the
      chemagic Magnetic Separation Module I was investigated. Analytical sensitivity
      for hepatitis C virus (HCV), human immunodeficiency virus-1 (HIV-1), hepatitis B
      virus (HBV), hepatitis A virus (HAV) and parvovirus B19 (B19) was compared to our
      present manual procedure that involves virus enrichment by centrifugation.
      RESULTS: Chemagic technology allows automation of the viral DNA/RNA extraction
      process. Viral nucleic acids were bound directly to magnetic beads from 9.6-ml
      minipools. By combining the automated magnetic beads-based extraction technology
      with our in-house TaqMan polymerase chain reaction (PCR) assays, 95% detection
      limits were 280 IU/ml for HCV, 4955 IU/ml for HIV-1, 249 IU/ml for HBV, 462 IU/ml
      for HAV and 460 IU/ml for B19, calculated for an individual donation in a pool of
      96 donors. The detection limits of our present method were 460 IU/ml for HCV, 879
      IU/ml for HIV-1, 90 IU/ml for HBV, 203 IU/ml for HAV and 314 IU/ml for B19.
      CONCLUSIONS: The 95% detection limits obtained by using the chemagic method were
      within the regulatory requirements for blood donor screening. The sensitivities
      detected for HCV, HBV, HAV and B19 were found to be in a range similar to that of
      the manual purification method. Sensitivity for HIV-1, however, was found to be
      inferior for the chemagic method in this study.

PMID- 16101687
TI  - Documented cases of post-transfusion malaria occurring in England: a review in
      relation to current and proposed donor-selection guidelines.
AB  - BACKGROUND AND OBJECTIVES: Although uncommon, five cases of transfusion
      transmitted malaria have been documented in England over the last 20 years. With
      the reappearance onto the market of high-quality malaria antibody assays, and by
      utilizing the results of analysis of these five cases, it has been possible to
      review the donor malaria-deferral guidelines. MATERIALS AND METHODS: Details of
      the five cases of post-transfusion malaria were reviewed against the proposed new
      donor-deferral guidelines for malaria. RESULTS: Three of the five cases of post
      transfusion malaria were directly attributable to the deferral guidelines,
      allowing infectious donors to be bled. CONCLUSIONS: The proposed new guidelines
      will prevent further cases of transmission from semi-immune individuals.

PMID- 16101688
TI  - Separation of whole blood into plasma and red cells by using a hollow-fibre
      filtration system.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to assess the separation of
      whole blood into red cells and plasma by using the Sangofer device, which is a
      gravity-fed, hollow-fibre system. The components would then be compared with
      those produced by the use of more elaborate technical equipment. MATERIALS AND
      METHODS: Ten whole-blood units were leucoreduced by using a WBF2 filter and
      immediately separated into red cells and plasma by using the Sangofer blood
      separation device. Red cells were stored in additive solution and tested on days
      1 and 42. The plasma was assayed for levels of various coagulation factors and
      for markers of both coagulation and complement activation. RESULTS: The red-cell
      parameters were similar to those obtained when routine centrifugation methods
      were used. The filter did not cause haemolysis. Levels of plasma factor VIII and
      factor XI were lower than those seen in routinely produced leucoreduced plasma
      units but there was no evidence of activation of the coagulation and complement
      systems. CONCLUSIONS: The Sangofer device is simple and straightforward to use
      and eliminates the need for both centrifugation and automated separation steps
      during the processing of whole blood into red cells and plasma components. Minor
      changes are required to make the procedure easier to incorporate into routine
      use.

PMID- 16101689
TI  - The use of a World Health Organization Transfusion Basic Information Sheet to
      evaluate transfusion practice in Croatia.
AB  - BACKGROUND AND OBJECTIVES: To assess the feasibility of using the World Health
      Organization (WHO) Transfusion Basic Information Sheet as a bedside tool for data
      collection and assessing transfusion practice. MATERIALS AND METHODS: A
      prospective 6-month audit of all transfusion episodes using the tool. RESULTS:
      Eight hundred and twenty-two forms were completed, capturing data on 59.7% of
      transfusion episodes. Completion of data fields was > 80%, except for the
      clinician's transfusion targets that were documented in only 58.5% of cases.
      Twenty per cent of patients received single red cell unit transfusions.
      CONCLUSIONS: The Basic Information Sheet can be incorporated into bedside
      clinical practice. We have identified the need to encourage clinicians to
      determine and document their transfusion targets before prescribing blood
      components.

PMID- 16101690
TI  - Transfusion practice in massively bleeding patients: time for a change?
AB  - BACKGROUND AND OBJECTIVES: We identified some fatal cases where massively
      bleeding patients received inadequate transfusion therapy. The aim of this study
      was to review and evaluate the transfusion practice in acutely multitransfused
      patients. MATERIALS AND METHODS: Patients receiving > 10 units of red blood cells
      (RBC) within 24 h of admission and 30 blood components within 7 days of admission
      were reviewed. RESULTS: Thirty-nine patients were identified, 13 of whom were
      inadequately transfused (IT) and had a higher mortality (12/13) than adequately
      transfused (AT) patients 13/26 (P = 0.013). Ten of 13 IT patients developed a
      microvascular bleed compared to four of 26 in the AT group (P = 0.001) and had a
      lower platelet count upon arrival at the intensive care unit (40 x 10(9)/l vs. 80
      x 10(9)/l, P = 0.024). CONCLUSIONS: An early balanced transfusion therapy is
      vital in massively bleeding patients, and a pro-active approach from the blood
      bank is warranted. We have introduced an acute transfusion package (ATP)
      consisting of 5 RBC, 5 FFP and 2 PC units, indicated in massively bleeding
      patients, securing a balanced transfusion therapy.

PMID- 16101691
TI  - Gamma irradiation does not affect 7-day storage of platelet concentrates.
AB  - BACKGROUND AND OBJECTIVES: Extension of storage of leucocyte-reduced platelet
      concentrates (LR-PCs) to 7 days has recently been introduced, but the effect of
      gamma irradiation on in vitro parameters was unknown. MATERIALS AND METHODS: A
      paired experiment was carried out, with gamma irradiation on day 1 or day 5 with
      25 Gy, and no irradiation served as a reference. RESULTS: Measurements during
      storage up to 8 days after blood collection showed no significant differences of
      irradiated LR-PCs vs. the control. CONCLUSIONS: Irradiation, either on day 1 or
      day 5, had no effect on platelet quality during a 7-day storage period.

PMID- 16101692
TI  - Collaborative study to establish the first international standard for
      quantitation of anti-HPA-1a.
AB  - BACKGROUND AND OBJECTIVES: This report describes the production of a freeze-dried
      preparation of pooled human plasma, containing immunoglobulin G (IgG) antibodies
      against the human platelet antigen 1a (HPA-1a). The material, coded 03/152, is
      proposed as an International Standard containing 100 arbitrary units of anti-HPA
      1a for use in quantitative assays to determine the anti-HPA-1a activity in
      clinical samples. MATERIALS AND METHODS: Plasma samples containing potent anti
      HPA-1a were pooled and freeze dried in 1-ml ampoules. In addition, three
      individual plasma samples were selected which had varying levels of anti-HPA-1a
      activity. The anti-HPA-1a activity of these three samples was determined by using
      a variety of quantitative assays with the proposed standard as a reference.
      RESULTS: An international collaborative study, which was part of the 2004 ISBT
      Platelet Immunology Workshop, involved 39 laboratories in 24 countries and showed
      that the anti-HPA-1a activity in three test samples could be reliably determined
      by using the proposed standard. CONCLUSIONS: Laboratories can use this standard
      to measure the anti-HPA-1a activity in patient's samples. Further studies are
      required to determine the relationship between anti-HPA-1a activity and clinical
      outcome in patients with neonatal alloimmune thrombocytopenia (NAIT).

PMID- 16101693
TI  - Report on the 12th International Society of Blood Transfusion platelet immunology
      workshop.
AB  - BACKGROUND AND OBJECTIVES: The aims of the 12th International Society of Blood
      Transfusion (ISBT) Platelet Immunology Workshop were to evaluate the proficiency
      of molecular human platelet antigen (HPA) genotyping and detection of platelet
      antibodies of unusual specificity or reactivity, to assess whether quantification
      of anti-HPA-1a is practicable, and to determine the variability of reagents and
      components used in the monoclonal antibody immobilization of platelet antigens
      assay (MAIPA). MATERIALS AND METHODS: Forty participants from 23 countries were
      sent 10 samples for DNA typing, five samples for antibody detection, a freeze
      dried anti-HPA-1a standard, three samples for anti-HPA-1a quantification and a
      MAIPA method questionnaire. RESULTS: The detection and identification of HPA
      antibodies varied from 2.7 to 95% of participants. The number of HPA genotyping
      errors per sample ranged from 0 to 3.96% per HPA loci. The majority of
      laboratories were able to assign an arbitrary number of units/ml of anti-HPA-1a
      activity to the unknown samples. The MAIPA questionnaire indicated a wide
      variation among participants, both in method and in reagents used. CONCLUSIONS:
      The results obtained from this workshop highlighted deficiencies in testing
      regimes and identified a need for internationally available reference materials.

PMID- 16101694
TI  - Prestorage leucofiltration prevents the accumulation of matrix metalloproteinase
      9 in red cell concentrates stored in mannitol-adenine-phosphate medium.

PMID- 16101695
TI  - Bacterial contamination of platelet components: remaining risks after
      introduction of bacterial screening.

PMID- 16101700
TI  - Do results from studies of a simulated epidural test dose improve our ability to
      detect unintentional epidural vascular puncture in children?

PMID- 16101701
TI  - Intraoperative pediatric blood transfusion therapy: a review of common issues.
      Part I: hematologic and physiologic differences from adults; metabolic and
      infectious risks.
AB  - Pediatric intraoperative transfusion therapy, particularly the approach to
      massive blood transfusion (blood loss > or =one blood volume) can be quite
      complex because of the unique relationship between the patient's blood volume and
      the volume of the individual blood product transfused. This paper is divided into
      two parts: part 1 presents an overview of the physiologic and hematologic
      differences between children and adults as well as an overview of the metabolic
      consequences of blood transfusions, risks of disease transmission, and blood
      compatibility issues.

PMID- 16101702
TI  - The correlation of the Narcotrend Index with endtidal sevoflurane concentrations
      and hemodynamic parameters in children.
AB  - BACKGROUND: The Narcotrend Index (NI) of anesthetic depth is potentially a
      pharmacodynamic measure of the effects of sevoflurane on the brain. METHODS: In
      this prospective observational study of 30 pediatric surgical patients (1-11
      years), we investigated the correlation between nonsteady-state endtidal
      sevoflurane (eT(Sevo)), NI, mean arterial pressure (MAP), and heart rate (HR).
      The performance of the Narcotrend for differentiation between consciousness and
      unconsciousness was evaluated using prediction probability (P(K)). RESULTS:
      Spearman correlation analysis showed significant correlations (P < 0.01) between
      eT(Sevo) and NI (r = -0.85) and MAP (r = -0.43). P(K)-values for differentiation
      between consciousness and unconsciousness were 1.0 for NI and <0.85 for MAP and
      HR. During the surgical procedure, NI-values showed a constant rise with each
      0.5% step of lowering eT(Sevo) (P < 0.03), whereas MAP remained unaltered and HR
      showed a constant decline (P < 0.03), except between 1.5 and 1%. CONCLUSIONS: In
      children, nonsteady-state eT(Sevo) concentrations are more closely related with
      NI than with MAP or HR. In this study, only NI reliably differentiated
      consciousness from unconsciousness.

PMID- 16101703
TI  - A randomized-controlled study of ultrasound prelocation vs anatomical landmark
      guided cannulation of the internal jugular vein in infants and children.
AB  - BACKGROUND: A specifically designed ultrasound scanner may be helpful in
      percutaneous cannulation of the internal jugular vein in pediatric patients. We
      report a new two-dimensional (2D) ultrasound prelocation (UL) technique using a
      transesophageal echocardiography (TEE) intraoperative probe instead of the
      portable scanner, and have compared the new technique with conventional
      anatomical landmark method (AL) for central venous catheterization in infants and
      children. METHODS: Sixty-two infants (body weight <12 kg) undergoing elective
      surgery for congenital heart disease were randomized into two groups. In the AL
      group, the landmark for cannulation was the palpation of the common carotid
      pulsation or the sternocleidomastoid triangle. In the UL group, the central vein
      was located by 2D ultrasonic imaging using a TEE intraoperative probe for HP
      SONOS 4500. The number of cannulation attempts, success rate, and complication
      rate were recorded. RESULTS: For the UL and AL groups, the cannulation success
      rate was 100% and 80% (P < 0.05), the incidence of arterial puncture was 3.1% and
      26.7% (P < 0.025), and the number of attempts was 1.57 +/- 1.04 and 2.55 +/- 1.76
      (P < 0.001), respectively. CONCLUSIONS: Two-dimensional ultrasound prelocated
      central venous catheterization in infants and children is convenient and can
      markedly increase cannulation success rate and reduce the incidence of
      complications.

PMID- 16101704
TI  - Pharmacokinetics and efficacy of ropivacaine for continuous epidural infusion in
      neonates and infants.
AB  - INTRODUCTION: The primary objective of this noncomparative study was to evaluate
      the pharmacokinetics of ropivacaine during a 48-72-h continuous epidural infusion
      of ropivacaine in children under 1 year. The secondary objectives were to assess
      efficacy and safety. METHODS: Neonates and infants (ASA I-III, gestational age >
      or =37 weeks, > or =2.5 kg, scheduled for major abdominal or thoracic surgery)
      were included and separated into age groups: 0-30 (neonate), 31-90, 91-180, and
      181-365 days. Ethics committee approval and informed parental consent were
      obtained before inclusion. An epidural catheter was introduced under general
      anesthesia at the appropriate dermatomal level. An initial bolus dose (0.9-2.0
      mg.kg(-1) of ropivacaine 0.2%) was followed by an epidural infusion (0.2 mg.kg(
      1).h(-1) for infants <180 days or 0.4 mg.kg(-1).h(-1) for infants >180 days).
      Plasma samples were collected every 12 h from 24 h, and on termination of the
      epidural infusion. Postoperative pain was evaluated using both the Objective Pain
      Scale and a four-graded descriptive scale. RESULTS: Forty-five infants, median
      age 116 (0-362) days, were included. Forty-three and 19 patients received an
      infusion for at least 48 and 72 h, respectively. Satisfactory analgesia was
      provided in the majority, only 20 patients were given supplementary medication
      during the infusion. In all age groups, plasma concentrations of unbound
      ropivacaine leveled at 24 h, without any further increase at 48 and 72 h. Because
      of lower clearance of unbound ropivacaine in neonates (mean 33 ml.min(-1).kg(-1))
      than in infants above the age of 30 days (80, 124, and 163 ml.min(-1).kg(-1),
      respectively, in the age groups 31-90, 91-180, and 180-365 days), unbound
      ropivacaine concentrations at the end of infusion were higher in neonates [median
      0.10 mg.l(-1) (0.04-0.21 mg.l(-1))] than in infants >30 days [median 0.03 mg.l(
      1) (0.003-0.10 mg.l(-1))]. CONCLUSION: Epidural infusions (0.2-0.4 mg.kg(-1).h(
      1) ropivacaine) provided satisfactory pain relief in neonates and infants under 1
      year. As plasma concentrations of unbound ropivacaine were not influenced by the
      duration of the infusion, ropivacaine can be safely used for postoperative
      epidural infusion for 48-72 h. Levels of unbound ropivacaine were higher in the
      neonates than in the infants, but were below threshold concentrations for CNS
      toxicity in adults (> or =0.35 mg.l(-1)). This should not preclude the use of
      ropivacaine infusions in neonates but suggests a need for caution during the
      first weeks of life.

PMID- 16101705
TI  - The temperature and humidity of inspired gases in infants using a pediatric
      circle system: effects of high and low-flow anesthesia.
AB  - BACKGROUND: The effects of low-flow anesthesia on the temperature and humidity of
      the inspired gas in infants during mechanical ventilation is unknown. This study
      was designed to evaluate the temperature and humidity of the inspired gas in
      infants using a pediatric circle absorber system with high and low fresh gas flow
      (HFGF and LFGF) anesthesia. METHODS: Twenty infants participated in this
      observational, sequential, cross-over study. Each infant was mechanically
      ventilated with a Kion Anesthesia Workstation, using a pediatric anesthesia
      circle circuit with both HFGF (6 l.min(-1)) and LFGF (0.6 l.min(-1)) technique.
      Airway temperature was recorded continuously at 16 sites throughout the breathing
      circuit. The relative humidity of the inspired gas was measured at the elbow
      connector adjacent to the CO2 sampling line. RESULTS: The mean airway
      temperatures of the inspired gas and the changes in mean airway temperatures
      throughout the breathing circuit during HFGF and LFGF did not differ
      significantly. The mean relative humidity of the inspired gas at steady state
      using a LFGF technique, 33.7 +/- 3.6%, was approximately threefold greater than
      it was with a HFGF technique, 11.9 +/- 5.1% (P < 0.05). CONCLUSIONS: Low-flow
      anesthesia with a pediatric circle system in infants neither increases the
      temperature of the inspired gas, nor achieves the minimum humidity of 50%
      reported to prevent ciliary damage, although the humidity during LFGF did
      increase threefold compared with HFGF. To maintain the temperature and humidity
      of the inspired gas during mechanical ventilation in infants, passive or active
      gas humidification should be used.

PMID- 16101706
TI  - Economic evaluation of ondansetron vs dimenhydrinate for prevention of
      postoperative vomiting in children undergoing strabismus surgery.
AB  - BACKGROUND: Although rarely life-threatening, postoperative vomiting (POV) is a
      distressing complication. The incidence of POV ranges from 34 to 90% in children
      undergoing strabismus surgery when antiemetics are not administered
      prophylactically. METHODS: In this study, a cost-consequence analysis (CCA) is
      used to estimate the economic benefit of ondansetron and dimenhydrinate as
      antiemetics administered prophylactically in children undergoing strabismus
      surgery. This retrospective study was conducted at The Hospital for Sick Children
      based on a review of 70 charts. RESULTS: Ondansetron was more effective with 45.3
      POV-free patients (PFP) in an adjusted cohort of 100, while dimenhydrinate
      resulted in 38.2 PFP in an adjusted cohort of 100. The costs were significantly
      different between the two groups, CAD dollars 185.90 (+/-26.37, 95% CI, CAD
      dollars 173,89; CAD dollars 197.90) and CAD dollars 232.90 (+/-CAD dollars 66.84,
      95% CI, CAD dollars 198.53; CAD dollars 267.27) per patient for ondansetron and
      dimenhydrinate, respectively. The length of stay in the postanesthetic care unit
      (PACU) represented over 97% of total costs, and the mean lengths of stay in the
      PACU for ondansetron and dimenhydrinate were significantly different, 3.43 and
      4.41 h, respectively. CONCLUSION: This study should serve as a pilot for a large
      scale investigation on the correlation between the length of stay in the PACU and
      the antiemetic agent used.

PMID- 16101707
TI  - Single-dose dexmedetomidine reduces agitation and provides smooth extubation
      after pediatric adenotonsillectomy.
AB  - BACKGROUND: Dexmedetomidine has shown sedative, analgesic, and anxiolytic effects
      after intravenous (IV) administration. Sevoflurane is associated with a high
      incidence of emergence agitation in preschool children. In this placebo
      controlled study, we examined the effect of single dose dexmedetomidine on
      emergence agitation in children undergoing adenotonsillectomy. METHODS: In a
      double-blinded trial, 60 children (age 3-7 years) were randomly assigned to
      receive dexmedetomidine 0.5 microg.kg(-1) IV or placebo, 5 min before the end of
      surgery. All patients received a standardized anesthetic regimen. For induction
      and maintenance of anesthesia we used sevoflurane. After surgery, the incidence
      and severity of agitation was measured 2 h postoperatively. The incidence of
      untoward airway events after extubation, such as breath holding, severe coughing,
      or straining were recorded. After surgery, the children's behavior and pain were
      assessed with a 5-point scale. RESULTS: The agitation and pain scores in the
      dexmedetomidine group were better than those in the placebo group (P < 0.05). The
      incidence of severe agitation (a score of 4 or more), and severe pain (a score of
      3 or more) were significantly less in the dexmedetomidine group (P < 0.05). The
      number of severe coughs per patient in the dexmedetomidine group was
      significantly decreased compared with the control group (P < 0.05). Postoperative
      vomiting was similar in both groups. Times to emergence and extubation were
      significantly longer in the dexmedetomidine group (P < 0.05). CONCLUSIONS: We
      conclude that 0.5 microg.kg(-1) dexmedetomidine reduces agitation after
      sevoflurane anesthesia in children undergoing adenotonsillectomy.

PMID- 16101708
TI  - Epidural abscess following epidural analgesia in pediatric patients.
AB  - Epidural abscess following epidural analgesia is an unusual event especially in
      pediatric patients. Two patients presented with fever and local signs of
      infection without neurological deficit on day 4 after the initiation of epidural
      analgesia. Neuro-imaging studies revealed epidural abscess. Both pediatric
      patients were treated successfully with intravenous antibiotics. One of the
      patients' initial MRI was normal. However, the symptoms persisted and a followed
      up scan revealed epidural abscess. The other patient presented with worsening
      local indurations over the epidural insertion site and positive blood culture
      with Hemolytic streptococcus. Our experience suggests that neuro-imaging study
      should be strongly considered to evaluate pediatric patients with suspicion of
      epidural abscess.

PMID- 16101709
TI  - Perioperative management of a child with short-chain acyl-CoA dehydrogenase
      deficiency.
AB  - Short-chain acyl-CoA dehydrogenase (SCAD) is a mitochondrial enzyme that
      catalyzes the dehydrogenation of short chain fatty acids (4 to 6 carbons in
      length) thereby initiating the cycle of beta-oxidation. This process generates
      acetyl-CoA, the key substrate for hepatic ketogenesis or ATP production by the
      Kreb's cycle. A deficiency of SCAD results in the build-up of potentially
      cytotoxic metabolites including ethylmalonic acid, methylsuccinyl CoA and butyryl
      carnitine. The end-organ involvement is heterogeneous, but most commonly includes
      hypotonia with possible lipid myopathy and developmental delay. Other reported
      complications include dysmorphic craniofacial features, hypoglycemia, seizures,
      scoliosis, hypertonia and hyperreflexia, cyclic vomiting and myocardial
      dysfunction. We present a 23-month-old girl with SCAD deficiency, who required
      posterior fossa decompression for type 1 Chiari malformation. The potential
      perioperative implications of SCAD deficiency are reviewed.

PMID- 16101710
TI  - Post dural puncture headache in a pediatric patient with idiopathic intracranial
      hypertension.
AB  - We describe the occurrence of postdural puncture headache (PPDH) in an adolescent
      with idiopathic intracranial hypertension (IIH) and its successful management
      with an epidural blood patch. PPDH is a very rare occurrence in patients with
      intracranial hypertension and is described as a paradoxical situation in the
      literature. There are only two previous case reports (in adults) of the possible
      association. A 15-year-old obese patient with a diagnosis of IIH had an
      uneventful diagnostic spinal tap using a 22G Quincke needle in the pediatric
      emergency department but returned 24 h later with PPDH. After a failed trial of
      conservative management, she had an uneventful but curative epidural blood patch
      with 15 ml of autologous venous blood and was able to return to school the day
      after the blood patch. Follow-up review by her neuro-ophthalmologist shows
      resolution of her headaches, considerable improvement in her visual field defect
      and resolution of papilledema. This is the first report of PPDH and its
      successful management with an epidural blood patch in a pediatric patient with
      IIH.

PMID- 16101711
TI  - Anesthetic management of a patient with asymptomatic ventricular tachycardia.
AB  - There are many causes of ventricular arrhythmias in pediatric patients, even
      those with structurally normal hearts. However, in young patients with 'normal'
      hearts, sustained ventricular arrhythmias are relatively rare. The primary
      concern of the physician is to identify which patients have benign ventricular
      arrhythmia patterns and which are at risk for sudden cardiac death. Even in
      asymptomatic patients, the choice of anesthetic agents may be important to
      minimize precipitation of episodes of tachyarrhythmias. This clinical report
      describes the anesthetic considerations for an asymptomatic child with a history
      of sustained premature ventricular contractions, ventricular tachycardia, and
      bigeminy. This child had chronic serous otitis media requiring repeat
      tympanostomy and tube replacement. This case report outlines the initial
      cancellation of anesthesia because of sustained arrhythmias, and subsequent
      conduct of the anesthesia for the case, as well as the considerations in the
      selection of the drugs when a child presents with significant ventricular
      arrhythmia.

PMID- 16101712
TI  - Jet ventilation for laryngotracheal surgery in an ex-premature infant.
AB  - A 4-month-old ex-premature infant with severe airway obstruction from subglottic
      cysts presented for surgical cyst removal. Laryngeal and tracheal surgical
      procedures in children may present difficulties for the anesthetist because the
      airway is shared with the surgeon. We report the use of high-frequency jet
      ventilation (HFJV) to maintain ventilation and provide adequate surgical access.
      Anesthesia was induced using sevoflurane in oxygen and was maintained with
      intravenous infusions of propofol 7.5 mg.kg(-1).h(-1) and remifentanil 0.4
      microg.kg(-1).min(-1). The suction channel of the ENT laryngoscope was used to
      introduce an 8-FG ureteric drainage catheter into the larynx and this catheter
      was used to provide HFJV. Obstruction to expiratory flow was a major concern and
      was dependent on good positioning of the rigid laryngoscope. Complications such
      as barotrauma, pneumopericardium, CO2-retention, necrotizing tracheobronchitis,
      and gastric rupture dictate a fastidious technique.

PMID- 16101713
TI  - Awake nasotracheal intubation using fiberoptic bronchoscope in a pediatric
      patient with Freeman-Sheldon syndrome.
AB  - The Freeman-Sheldon syndrome is a congenital disease primarily affecting the
      facial, limb and respiratory muscles that give rise to classical clinical
      features including typical whistling face and short webbed neck associated with
      difficult intubation. We present successful awake nasotracheal intubation in a 6
      year-old patient with typical clinical features of Freeman-Sheldon syndrome by
      using fiberoptic bronchoscope on two separate occasions.

PMID- 16101714
TI  - Surgical face mask as a nappy!

PMID- 16101715
TI  - A rose by any other name.

PMID- 16101717
TI  - Sevoflurane anesthesia for sedation in the MRI suite.

PMID- 16101719
TI  - MRI sedation.

PMID- 16101722
TI  - Laparoscopy for living donor nephrectomy--particularities of the currently
      applied techniques.
AB  - Today, laparoscopic donor nephrectomy (LDN) in many centers features the standard
      approach for kidney retrieval in living donors. More than 60% of the centers in
      the USA currently perform LDN and numbers are rising in Europe as well. Today's
      variety of laparoscopic approaches reflects the evolution in the field of LDN.
      Multiple modifications have been made for the laparoscopic approach, with
      consequences for intraoperative handling of the kidney, operating and ischemic
      times and with impact on donor, organ, and recipient. We reviewed the literature
      from 1995 to 2004 and critically evaluated the different technical modifications,
      their specific advantages and disadvantages and their impact for the operation.
      The article aims to help the surgeon choose the technique he feels most safe with
      for performing laparoscopic kidney retrieval safely and with good results for
      donor and recipient.

PMID- 16101723
TI  - Bone metabolism in renal transplant patients treated with cyclosporine or
      sirolimus.
AB  - Sirolimus is a new immunosuppressive agent used as treatment to prevent acute
      renal allograft rejection. One of the complications of renal transplantation and
      subsequent long-term immunosuppression is bone loss associated with osteoporosis
      and consequent fracture. Two open-label, randomized, phase 2 studies comparing
      sirolimus versus cyclosporine (CsA) included indices of bone metabolism as
      secondary end-points. Markers of bone turnover, serum osteocalcin and urinary N
      telopeptides, were measured over a 1-year period in 115 patients receiving either
      CsA or sirolimus as a primary therapy in combination with azathioprine and
      glucocorticoids (study A) or mycophenolate mofetil (MMF) and glucocorticoids
      (study B). Urinary excretion of N-telopeptides and the concentrations of serum
      osteocalcin were consistently higher in the CsA-treated patients and
      significantly different at week 24 for N-telopeptides and at weeks 12, 24, and 52
      for osteocalcin. In conclusion, future trials are warranted to test whether a
      sirolimus-based regimen conserves bone mineral density compared with a CsA-based
      regimen.

PMID- 16101724
TI  - Morphological and functional differences in haemostatic axis between kidney
      transplanted and end-stage renal disease patients.
AB  - End-stage renal disease (ESRD) is characterized by several atherothrombotic
      abnormalities, and kidney transplant seems to improve most of them. However,
      because it is not clear which mechanism is responsible for such improvement, our
      purpose was to clarify that point.We conducted a cross sectional study involving
      30 ESRD patients, 30 ESRD kidney-transplanted patients (Ktx) and 30 healthy
      controls (C) to evaluate platelet morphology and function, atherothrombotic
      profile, endothelial abnormalities and cytokine levels involved in the insulin
      resistance/endothelial dysfunction. (i) Platelet morphology: The ESRD group
      showed platelet size similar to the other two groups (ESRD=3518x10(3)+/-549x10(3)
      nm2, C=3075x10(3)+/-197x10(3) nm2, Ktx=2862x10(3)+/-205x10(3) nm2) with similar
      platelet granules and number. (ii) Platelet surface glycoprotein: The CD41 and P
      Selectin were similar between groups. (iii) Platelet intracellular calcium:
      Resting intracellular calcium was statistically higher in ESRD compared to the C
      group (ESRD=182.1+/-34.5, Ktx=126.7+/-14.1, C=72.0+/-11.0 nM, P<0.01). (iv)
      Hypercoagulability markers and natural anticoagulants: The Ktx and ESRD groups
      showed higher levels of hypercoagulability markers compared to the C group. A
      reduction in antithrombin activity was evident in ESRD compared to the Ktx group
      (P=0.03). (v) Endothelial morphology: The ESRD group showed a thickened vessel
      basal membrane compared to the Ktx and C groups with more endothelial sufference.
      (vi) Insulin resistance and pro-inflammatory cytokine profile: The ESRD showed a
      higher homeostasis model assessment provided equations for estimating insulin
      resistance (HOMA-IR) compared to the Ktx and C groups (ESRD=2.6+/-0.3, Ktx=1.8+/
      0.2, C=1.1+/-0.1, P=0.005) and increased soluble tumor neurosis factor alpha
      (sTNFalpha) (P<0.05) and soluble vascular cell adhesion molecule (sVCAM) levels
      (P<0.01). Positive correlations were evident among HOMA-IR and sTNFalpha
      (P<0.001) and sVCAM (P=0.01), respectively. In a small subgroup of ESRD who
      underwent Ktx (five pts), our findings were confirmed at 1 year of follow-up,
      suggesting an improvement of almost haemostatic abnormalities. Kidney transplant
      is associated with a better atherothrombotic profile in ESRD, platelet
      intracellular calcium and cytokines seem to be most influenced by the transplant,
      while most morphological abnormalities are retained.

PMID- 16101725
TI  - Nocardiosis following solid organ transplantation: a single-centre experience.
AB  - Nocardiosis is a localized or disseminated bacterial infection caused by aerobic
      Actinomyces that commonly affects immunocompromised hosts. The aim of this study
      was to retrospectively review clinical course and outcome of nocardiosis in solid
      organ recipients at our centre. Five cases of nocardiosis were identified in a
      series of more than 4000 consecutive solid organ transplants performed at
      Innsbruck university hospital during a 25-year period. Of the five patients with
      nocardiosis, two had undergone multivisceral, one liver, one kidney and one lung
      transplantation. Three patients with Nocardia asteroides infection were treated
      successfully and recovered from their infectious disease, however, one lost his
      renal graft following withdrawal of immunosuppression. The lung recipient
      recovered from nocardiosis but died later on from Pseudomonas pneumonia. One
      multivisceral recipient died from Nocardia farcinica-disseminated infection.
      Nocardiosis is a rare, difficult-to-diagnose-and-treat complication following
      solid organ transplantation. Intestinal recipients might be at increased risk to
      develop this infection.

PMID- 16101726
TI  - Progression of macrovascular diseases is reduced in type 1 diabetic patients
      after more than 5 years successful combined pancreas-kidney transplantation in
      comparison to kidney transplantation alone.
AB  - Recent reports have demonstrated an improved cardiovascular outcome after
      simultaneous pancreas-kidney transplantation (SPKT) compared with kidney
      transplantation alone (KTA) in type 1 diabetic patients with end-stage renal
      disease. The purpose of this study was to determine the impact of SKPT and KTA on
      the progression of cerebrovascular disease (CVD), coronary heart disease (CHD)
      and peripheral vascular disease (PVD) 5 and 10 years after transplantation. Only
      patients with graft survival more than 5 years, were included in this study. In
      summary, 12 type 1 diabetic patients with SPKT and 10 diabetic subjects with KTA
      were evaluated. The immunosuppressive therapy was similar in both patient groups.
      The mean observation period was 124 (72-184) months in the SPKT group and 122 (64
      216) months in the group with KTA. To investigate the vascular risk profile we
      examined mean HbA1c, blood pressure and lipid levels in both patient groups
      during the first 5 years (period I) and the second 5 years (period II) after
      transplantation (measurements at least at 3-month intervals). Additionally, we
      evaluated the prevalence of moderate (stage I-II) and severe (stage III-IV)
      macrovascular diseases prior as well as 5 and 10 years after transplantation.
      During period I the mean HbA1c-value was 5.7+/-0.4% in the group with SPKT versus
      7.4+/-0.8% in the KTA group, and in period II 5.8+/-0.4% in the SPKT group versus
      7.6+/-0.9% (P<0.001) in the patients with KTA. The cholesterol levels were
      approximately the same in both groups, the triglycerides were lower in the
      patients with SPKT than in the subjects with KTA with 1.3+/-0.4 vs. 2.2+/-0.9
      mmol/l in period I, and 1.4+/-0.5 vs. 2.3+/-0.6 mmol/l in period II (P<0.05). The
      BP-values were similar in both groups. Five years after transplantation the
      prevalence of vascular diseases was not significantly different between both
      groups. During the following 5 years the prevalence of macrovascular diseases
      increased more in the KTA than in the SKPT group. After a mean observation period
      of 10 years the SKPT group showed a lower prevalence of vascular diseases (stage
      I-IV) with 41% CVD, 50% CHD and 50% PAV in comparison to the KTA group with a
      prevalence of 80% CVD, 90% CHD and 80% PAV), the difference was not statistically
      significant because of the small patient groups. The frequency of the vascular
      complications myocardial infarction (16% vs. 50%), stroke (16% vs. 40%) and
      amputations (16% vs. 30%) was in summary significant lower in the patients with
      SPKT than in the patients with KTA (P<0.05). In conclusion, while for the first 5
      years after transplantation the progression of macroangiopathy in patients with
      SPKT and KTA was not significantly different, after a mean 10-year observation
      period the progression of macrovascular diseases was significantly lower in
      recipients with a functioning SPKT compared to patients with a KTA; this can be
      explained by a better vascular risk profile after SPKT. The 10-year patient
      survival was 83% in the SPKT group and 70% in patients with KTA.

PMID- 16101727
TI  - Resolution of hypophosphatemia is associated with recovery of hepatic function in
      children with fulminant hepatic failure.
AB  - Fulminant hepatic failure (FHF) is a rare but often fatal disease in children.
      Clinical and laboratory predictors of liver regeneration and recovery, however,
      have not been well established. We hypothesized that hypophosphatemia may
      indicate recovery of liver synthetic function in children with FHF. We
      retrospectively reviewed the medical records of children with FHF who were
      admitted to UCLA and recovered hepatic function either spontaneously or by liver
      transplantation (LTx). Serum phosphate (Ph) and prothrombin time or international
      normalized ratio (INR) were compared over the patient's clinical course. Records
      of 39 children who spontaneously recovered experienced profound hypophosphatemia
      that resolved as liver synthetic function improved. Similar patterns were seen in
      the 84 children who recovered after LTx. We found that hypophosphatemia precedes
      the recovery of liver synthetic function in children with FHF who recovered with
      or without transplantation, and that Ph levels return to normal as liver
      synthetic function improves. These data suggest that hypophosphatemia may be a
      useful laboratory indicator of recovering liver function in children with FHF.

PMID- 16101728
TI  - A retrospective study of the prognostic impact of cytokine secretion in mixed
      lymphocyte culture on long-term graft function following allogeneic renal
      transplantation.
AB  - We have previously shown that in vitro measurement of cytokine production prior
      to renal transplantation can provide predictive information on the risk of acute
      rejection. Our earlier studies demonstrated that patients who secreted high
      levels of interferon-gamma (IFN-gamma) in OKT3-stimulated or mixed lymphocyte
      culture had a significantly increased risk of acute rejection compared with
      patients who secreted lower levels. In this study, we performed a retrospective
      analysis of the same cohort of patients in order to determine the prognostic
      value of cytokine profiles and other variables on long-term graft function. Our
      results show that high levels of IFN-gamma in pretransplant mixed lymphocyte
      culture are a highly significant predictor of poorer creatinine levels at 18, 24
      and 36 months post-transplant.

PMID- 16101729
TI  - Prevalence and characteristics of noncompliant behaviour and its risk factors in
      kidney transplant recipients.
AB  - Noncompliance with therapy is one possible explanation for the observation that
      long-term graft survival is not sufficiently improved by the development in
      immunosuppression. The aim of the study was to explore the prevalence,
      characteristics and risk factors of noncompliance with immunosuppression. A total
      of 161 adult kidney transplant recipients were interviewed about their self-rated
      health, social support, education, stress from adverse effects and compliance
      with the immunosuppression. The prevalence of subclinical noncompliance was 54%.
      Noncompliant patients declared significantly worse self-rated health, less
      satisfaction with social support and higher stress from adverse effects. Male
      gender (OR 7.5, CI 2.4-23.39), high stress from adverse effects (OR 12.27, CI
      2.44-61.88), fair self-rated health (OR 4.45, CI 1.04-19.55) and fair
      satisfaction with social support (OR 4.55, CI 1.08-19.24) were predictors of
      noncompliance. Standardized detection methods should be developed with the aim of
      identifying patients who are at risk of noncompliance in order to prevent graft
      loss.

PMID- 16101730
TI  - Benefit of Kupffer cell modulation with glycine versus Kupffer cell depletion
      after liver transplantation in the rat: effects on postischemic reperfusion
      injury, apoptotic cell death graft regeneration and survival.
AB  - Inhibition or destruction of Kupffer cells (KC) may protect against ischemia
      reperfusion (IR) induced primary graft nonfunction (PNF) in liver
      transplantation. Besides KC activation, PNF is characterized by microvascular
      perfusion failure, intrahepatic leukocyte accumulation, cell death and
      hepatocellular dysfunction. KCs can be inactivated by different agents including
      gadolinium chloride (GdCl3), methyl palmitate (MP) and glycine. The effects of
      three KC inactivators on IR-injury after rat liver transplantation were compared
      in the present study. Lewis liver donors were treated with GdCl3, MP, glycine or
      saline (control). Liver grafts were transplanted following 24 h storage (UW
      solution). KC populations and IR damage were assessed by histologic analysis,
      quantitative real-time polymerase chain reaction (RT-PCR) and intravital
      microscopy. The number of hepatic ED-1 positive macrophages was diminished after
      GdCl3 (114.8+/-4.4/mm2 liver tissue) and MP treatment (176.0+/-5.0), versus the
      glycine (263.9+/-5.5) and control (272.1+/-5.6) groups. All three treatment
      modalities downregulated phagocytic activity for latex particles, paralleled by
      reduced microvascular injury (acinar perfusion index, GdCl3: 0.75+/-0.03; MP:
      0.83+/-.03; glycine: 0.84+/-0.03; 0.63+/-0.03). Quantitative RT-PCR revealed
      elevated myeloperoxidase mRNA after glycine versus GdCl3 and MP pretreatment (3.2
      and 3.4-fold, P=0.011, respectively), without difference to controls (2.9-fold
      of glycine). TNFalpha-mRNA was reduced after glycine- (5.2-fold), GdCl3- (19.7
      fold), MP-treatment (39.5-fold) compared with controls. However, profound
      prevention of intrahepatic cell death and liver graft failure was solely achieved
      with glycine preconditioning. Different than GdCl3 and MP, glycine modulates
      rather than destroys KCs. Glycine appears to preserve cell viability and to
      TNFalpha/leukocyte dependent organ regeneration capacity, which is related to
      increase graft survival following liver transplantation.

PMID- 16101731
TI  - Immune cells in a heterotopic lamb-to-pig bronchial xenograft model.
AB  - We developed our porcine model to elucidate the cellular rejection mechanisms of
      xenografts. Bronchial segments from a donor lamb were implanted into domestic
      pigs. The immunosuppressive regimens consisted of no immusuppression, or of daily
      oral cyclosporine A (CsA) 15 mg/kg, or of everolimus, 1.5 mg/kg, or of both.
      Implants were serially harvested during 17 days. Epithelial damage and
      obliteration were graded histologically, followed by a count of CD4+, CD8+, MHC
      class II-expressing cells, and macrophages. Furthermore, we studied the
      pharmocokinetics of everolismus. Epithelial damage preceded luminal obliteration,
      which was eventually total, except when both drugs had been given. In xenografts,
      an influx of cells with CD8+ cells dominating peaked on day 9, thereafter
      declining, except in the combination drug group. There, the immunological
      reaction was delayed and blunted, with CD4+ cells dominating. More macrophages
      appeared in xenografts than in allografts except with the combination CsA and
      everolimus. A dose of 1.5 mg/kg everolimus yields adequate blood concentrations
      for porcine studies. In this xenograft model, chronic rejection appears to be
      caused by an immune response to the graft, but it is more short-lived than the
      response in allografts. The combination of CsA and everolimus was able to blunt
      the response and delay the subsequent obliteration.

PMID- 16101732
TI  - Donor transmitted anaplastic carcinoma in a kidney-transplant recipient.
AB  - With the more frequent use of organs from elderly donors, the risk of
      transmitting tumor cells to the recipient increases. We report a case in which
      anaplastic carcinoma tumor cells from an organ-donor were transmitted to a kidney
      transplantation recipient. The donor's metastatic disease was discovered 7 days
      after harvest of the kidney following a brain biopsy undertaken at admission of
      the donor. The risk of transmitting the disease was generally estimated as so
      small that the excellently functioning kidney was not removed. Twelve weeks
      later, however, malignant cells were found in a biopsy of the transplanted
      kidney. The organ was removed immediately, but the intraoperative situs showed
      advanced disease with lymph-node-metastasis. Twelve months later no tumor
      progress could be detected. This case shows that there is considerable risk of
      transmitting formerly undetected cancer in elderly donors. Autopsies of donors
      who are older than 60 years of age should be routinely performed after organ
      donation.

PMID- 16101733
TI  - Recurrence of in-stent restenosis in cardiac allograft vasculopathy following
      implantation of a sirolimus-eluting stent.
AB  - Coronary lesions in patients with advanced cardiac allograft vasculopathy (CAV)
      are frequently treated with percutaneous coronary intervention. Despite high
      primary success rates, long-term outcome is significantly impaired by a high
      incidence of restenosis. In nontransplanted patients, the use of drug-eluting
      stents (DES) significantly decreases the rate of coronary in-stent restenosis. We
      report a case treated for cardiac allograft coronary in-stent restenosis with a
      sirolimus-eluting stent presenting with recurrent in-stent restenosis at follow
      up. However, the pattern of in-stent restenosis changed from diffuse
      proliferative disease in the bare-metal stent to a focal pattern in the sirolimus
      eluting stent concordant with observations in nontransplanted patients. This case
      highlights the need for further studies addressing the effect of DES for the
      prevention of restenosis both in de novo as well as in-stent restenotic lesions
      in patients with CAV.

PMID- 16101734
TI  - Interleukin 2 receptor blockers may directly inhibit lymphocyte mediated
      ischaemia reperfusion injury.

PMID- 16101735
TI  - Relapsing cutaneous Mycobacterium chelonae infection in a lung transplant
      patient.

PMID- 16101736
TI  - Transient maternal hypothyroxinemia at onset of corticogenesis alters tangential
      migration of medial ganglionic eminence-derived neurons.
AB  - Correct positioning of cortical neurons during development depends on the radial
      migration of the projection neurons and on the coordinated tangential and radial
      migrations of the subcortically generated interneurons. As previously shown, a
      transient and moderate maternal deficiency in thyroxin during early
      corticogenesis alters the radial migration of projection neurons. To determine if
      a similar effect might also affect tangential migration of medial ganglionic
      eminence (MGE)-derived neurons at the origin of cortical interneurons, explants
      of MGE from green fluorescent protein (GFP)-transgenic embryos were implanted
      into flat cortical mounts from wild-type embryos. The distances covered and the
      preferential migration (medially) of GFP-MGE neurons from embryos of
      hypothyroxinemic dams are not affected in their tangential migration into wild
      type control cortices. In contrast, when GFP-MGE neurons from embryos of control
      or hypothyroxinemic dams migrate within cortices from embryos of hypothyroxinemic
      dams, the GFP-MGE-derived neurons lose their preferential direction of migration,
      although they still migrate for long distances throughout the cortex. Our results
      show that maternal hypothyroxinemia alters the tangential migration of GFP-MGE
      derived neurons in the neocortex of the progeny and suggest that this alteration
      is not derived from the migratory neurons themselves but through undefined short-
      and long-range cues responsible for the guidance of their migration.

PMID- 16101737
TI  - Membrane-associated guidance cues direct the innervation of forebrain and
      midbrain by dorsal raphe-derived serotonergic axons.
AB  - Unlike many neurons that extend an axon precisely to a single target, individual
      dorsal raphe 5-HT neurons project to multiple brain regions and their axon
      terminals often lack classical synaptic specializations. It is not known how 5-HT
      axon collaterals select between multiple target fields, or even if 5-HT axons
      require specific guidance cues to innervate their targets. Nor is it known how
      these axon collaterals are restrained within specific innervation target regions.
      To investigate this, we challenged explants of dorsal raphe with co-explants, or
      cell membrane preparations of ventral midbrain, striatum or cerebral cortex. We
      provide evidence for membrane-associated cues that promote 5-HT axon growth into
      each of these three target regions. The axon growth-promoting activity was heat-,
      protease- and phosphatidylinositol-phospholipase-C (PI-PLC)-sensitive.
      Interestingly, 5-HT axons specifically lost the ability to grow in heterotypic
      explants, or membrane carpets, following contact with ventral midbrain or
      striatal, but not cortical, explants or membranes. This inductive activity
      associated with striatal and ventral midbrain membranes was sensitive to both
      high salt extraction and PI-PLC treatment. By contrast, the activity that
      inhibited 5-HT axon growth onto heterotypic membranes was sensitive only to high
      salt extraction. These results provide evidence that a
      glycosylphosphatidylinositol (GPI)-linked membrane protein promotes 5-HT axon
      growth, and that short-range membrane-bound, as well as GPI-linked, molecules
      contribute to the guidance of 5-HT axon collaterals. These findings suggest that
      5-HT axon collaterals acquire a target-induced growth-inhibitory response to
      alternative targets, increasing their selectivity for the newly innervated field.

PMID- 16101738
TI  - Voltage-gated potassium channels regulate the response of retinal growth cones to
      axon extension and guidance cues.
AB  - Xenopus retinal ganglion cell growth cones express various voltage-gated
      potassium (Kv) channels. We showed previously that 4-aminopyridine and
      tetraethylammonium have different effects on the outward currents of embryonic
      Xenopus retinal ganglion cells. Therefore, we asked whether these Kv channel
      inhibitors differentially regulate the response of retinal ganglion cell growth
      cones to extrinsic cues. First, we tested the role of Kv channels in axon
      extension mediated by a substrate bound cue and found that 4-aminopyridine
      blocked, whereas tetraethylammonium enhanced basal extension on laminin. Yet,
      when the growth cones were stimulated to extend with application of soluble
      growth factors, both inhibitors resulted in a return to the basal extension rates
      observed in the presence of laminin alone. Second, we asked if Kv channels
      modulate the response of retinal ganglion cell growth cones to a guidance cue,
      the chemorepellent fibroblast growth factor-2. When presented in a gradient to
      one side of the growth cone, fibroblast growth factor-2 repulsed retinal ganglion
      cell growth cones in the presence of 4-aminopyridine but not tetraethylammonium.
      These data argue that tetraethylammonium- and 4-aminopyridine-sensitive Kv
      channels differ in the manner by which they regulate the response of retinal
      ganglion cell axons to extension and guidance cues. Non-ratiometric calcium
      imaging indicated that differences in the ability of tetraethylammonium- and 4
      aminopyridine-sensitive Kv channels to regulate calcium activity within the
      growth cone may underlie their unique modulation of growth cone behaviour.

PMID- 16101739
TI  - Purkinje cell spinogenesis during architectural rewiring in the mature
      cerebellum.
AB  - Spines can grow and retract within hours of activity perturbation. We
      investigated the time course of spine formation in a model of plasticity
      involving changes in brain architecture where spines of a dendritic domain become
      innervated by a different neuronal population. Following a lesion of rat
      olivocerebellar axons, by severing the inferior cerebellar peduncle, new spines
      grow on the deafferented proximal dendrite of the Purkinje cells (PCs) and these
      new spines become innervated by parallel fibres (PFs) that normally contact only
      the distal dendrites. The varicosities of climbing fibre (CF) terminal arbors
      disappear within 3 days of the lesion. Spine density in the proximal dendritic
      domain begins to rise within 3 days and continues to increase towards a plateau
      at 6-8 days. In 'slow Wallerian degeneration' mice, in which axonal degeneration
      is delayed, climbing fibre varicosities virtually disappear at 14 rather than 3
      days. Spine density in the proximal dendritic domain is similar to control
      Purkinje cells up to 14 days and increases significantly 18 days postlesion. The
      delayed spinogenesis in the latter mutant is the result of a persistence of the
      climbing fibre presynaptic structure in the absence of activity. Therefore,
      climbing fibre activity itself is not directly responsible for the suppression of
      spine formation, but suppression mechanisms tend to become weaker as long as the
      structural dismantling of the presynaptic varicosities proceeds. Thus,
      spinogenesis is guided by two different mechanisms; a rapid one related to
      changes in homotypic remodeling and a slower one, which requires the removal of a
      competitive afferent.

PMID- 16101740
TI  - Effect of combined treatment with methylprednisolone and soluble Nogo-66 receptor
      after rat spinal cord injury.
AB  - Methylprednisolone (MP) is a synthetic glucocorticoid used for the treatment of
      spinal cord injury (SCI). Soluble Nogo-66 receptor (NgR) ectodomain is a novel
      experimental therapy for SCI that promotes axonal regeneration by blocking the
      growth inhibitory effects of myelin constituents in the adult central nervous
      system. To evaluate the potential complementarity of these mechanistically
      distinct pharmacological reagents we compared their effects alone and in
      combination after thoracic (T7) dorsal hemisection in the rat. Treatment with an
      ecto-domain of the rat NgR (27-310) fused to a rat IgG [NgR(310)ecto-Fc] (50
      microm intrathecal, 0.25 microL/h for 28 days) or MP alone (30 mg/kg i.v., 0, 4
      and 8 h postinjury) improved the rate and extent of functional recovery measured
      using Basso, Beattie, Bresnahan (BBB) scoring and footprint analysis. The effect
      of MP treatment on BBB score was apparent the day after SCI whereas the effect of
      NgR(310)ecto-Fc was not apparent until 2 weeks after SCI. NgR(310)ecto-Fc or MP
      treatment resulted in increased axonal sprouting and/or regeneration, quantified
      by counting biotin dextran amine-labeled corticospinal tract axons, and increased
      the number of axons contacting motor neurons in the ventral horn gray matter
      caudal to the lesion. Combined treatment with NgR(310)ecto-Fc and MP had a more
      pronounced effect on recovery of function and axonal growth compared with either
      treatment alone. The data demonstrate that NgR(310)ecto-Fc and MP act in a
      temporally and mechanistically distinct manner and suggest that they may have
      complementary effects.

PMID- 16101741
TI  - Neurturin has multiple neurotrophic effects on adult rat sacral parasympathetic
      ganglion neurons.
AB  - Neurturin (NTN) is an important neurotrophic factor for parasympathetic neurons;
      however, no studies to date have investigated the signalling mechanisms
      downstream of GFRalpha2 and Ret activation underlying this neurotrophic support.
      This is particularly important for pelvic parasympathetic neurons, which are
      prone to injury during surgical procedures such as prostatectomy, and where there
      are no current therapies for axonal regeneration. To address this issue we have
      cultured dissociated adult rat pelvic ganglion neurons and also examined the
      structural changes in pelvic ganglion neurons after axotomy. Axotomised penile
      neurons deprived of target-derived support had smaller somata than intact
      neurons. Studies of cultured adult pelvic ganglion neurons also demonstrated that
      NTN stimulated soma growth. Further experiments showed that NTN reduced the up
      regulation of tyrosine hydroxylase expression in cultured pelvic parasympathetic
      neurons. NTN stimulated the extension of neurites in cultured parasympathetic,
      but not sympathetic, pelvic ganglion neurons. Inhibition of phosphatidylinositol
      3-kinase prevented initiation of neurite outgrowth, whereas inhibition of the
      mitogen-activated protein kinase and the Src family kinase pathways disrupted NTN
      stimulated microtubule assembly. Surprisingly, NTN did not activate the
      transcription factor cAMP-response element binding protein (CREB), which is
      typically involved in neurotrophic signalling in sympathetic neurons. This is the
      first study to identify signalling pathways activated by NTN in adult
      parasympathetic neurons. Our results may lead to a better understanding of
      regenerative mechanisms in parasympathetic neurons, especially for those
      innervating urogenital organs. Our results also indicate that neurotrophic
      signalling in parasympathetic neurons is different from that in other types of
      peripheral neurons.

PMID- 16101742
TI  - Loss of connexin36 increases retinal cell vulnerability to secondary cell loss.
AB  - Accruing evidence indicates that gap junctions are involved in neuronal survival
      after brain injury. The present study was aimed at clarifying the contribution of
      the neuronal gap-junction protein connexin36 (Cx36) to secondary cell loss after
      injury in the mouse retina. A focal retinal lesion was induced by infrared laser
      photocoagulation. Remarkably, this model allowed spatial and temporal definition
      of the lesion with high reproducibility. Moreover, Cx36 is abundantly expressed
      in the retina and plays an essential role in the visual transmission process.
      Taking advantage of these features, cell death was assessed using TUNEL assay and
      light and electron microscopy, and the extent of Cx36 expression was studied by
      immunohistochemistry, Western blot, in situ hybridization and real-time RT-PCR.
      Secondary cell loss was most prominent between 24 and 48 h after lesioning. This
      peak was accompanied by an increase in Cx36 expression. When cultured explanted
      retinas were subjected to gap-junction blockers a significant increase in the
      extent of secondary cell loss after laser photocoagulation became evident. Using
      the same experimental paradigm we compared the incidence of cell death in wild
      type and Cx36(-/-) mice. A significant increase in total number of TUNEL-positive
      cells occurred in the Cx36(-/-) mice compared to controls. From these data we
      conclude that Cx36 contributes to the survival and resistance against damage of
      retinal cells and thus constitutes a protective factor after traumatic injury of
      the retina.

PMID- 16101743
TI  - Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases
      NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease.
AB  - Epidemiological data indicate that low n-3 polyunsaturated fatty acids (PFA)
      intake is a readily manipulated dietary risk factor for Alzheimer's disease (AD).
      Studies in animals confirm the deleterious effect of n-3 PFA depletion on
      cognition and on dendritic scaffold proteins. Here, we show that in transgenic
      mice overexpressing the human AD gene APPswe (Tg2576), safflower oil-induced n-3
      PFA deficiency caused a decrease in N-methyl-D-aspartate (NMDA) receptor
      subunits, NR2A and NR2B, in the cortex and hippocampus with no loss of the
      presynaptic markers, synaptophysin and synaptosomal-associated protein 25 (SNAP
      25). n-3 PFA depletion also decreased the NR1 subunit in the hippocampus and
      Ca2+/calmodulin-dependent protein kinase (CaMKII) in the cortex of Tg2576 mice.
      These effects of dietary n-3 PFA deficiency were greatly amplified in Tg2576 mice
      compared to nontransgenic mice. Loss of the NR2B receptor subunit was not
      explained by changes in mRNA expression, but correlated with p85alpha
      phosphatidylinositol 3-kinase levels. Most interestingly, n-3 PFA deficiency
      dramatically increased levels of protein fragments, corresponding to
      caspase/calpain-cleaved fodrin and gelsolin in Tg2576 mice. This effect was
      minimal in nontransgenic mice suggesting that n-3 PFA depletion potentiated
      caspase activation in the Tg2576 mouse model of AD. Dietary supplementation with
      docosahexaenoic acid (DHA; 22 : 6n-3) partly protected from NMDA receptor subunit
      loss and accumulation of fodrin and gelsolin fragments but fully prevented CaMKII
      decrease. The marked effect of dietary n-3 PFA on NMDA receptors and
      caspase/calpain activation in the cortex of an animal model of AD provide new
      insights into how dietary essential fatty acids may influence cognition and AD
      risk.

PMID- 16101744
TI  - Activation of cerebellar parallel fibers monitored in transgenic mice expressing
      a fluorescent Ca2+ indicator protein.
AB  - Genetically encoded fluorescent Ca2+ indicator proteins (FCIPs) are promising
      tools to study Ca2+ signaling in large assemblies of nerve cells. Currently,
      there are few examples of stable transgenic mouse lines that functionally express
      such sensors in well-defined neuronal cell populations. Here we report the
      generation and characterization of transgenic mice expressing an FCIP under the
      5' regulatory sequences of the Kv3.1 potassium channel promoter. In the
      cerebellar cortex, expression was restricted to granule cells. We first
      demonstrated reliable measurements of Ca2+ transients from beams of parallel
      fibers and compared the FCIP signals with intrinsic autofluorescence signals. We
      demonstrate that, in a transgenic line that exhibits a high expression level of
      the FCIP, autofluorescence signals are negligible and stimulation-induced
      fluorescence transients represent FCIP signals. Using frontal cerebellar slices
      we imaged antidromic activation of granule cells following electrical stimulation
      of parallel fibers and orthodromic activation of beams of parallel fibers
      following electrical stimulation of granule cells. We found that paired pulse
      induced presynaptic Ca2+ transients of parallel fibers are not affected by
      blockade of N-methyl-D-aspartate receptors.

PMID- 16101745
TI  - Inhibitory glutamate receptors in spider peripheral mechanosensory neurons.
AB  - Most mechanosensory neurons are inhibited by GABAergic efferent neurons. This
      inhibition is often presynaptic and mediated by ionotropic GABA receptors at the
      axon terminals. GABA receptor activation opens Cl- channels, leading to membrane
      depolarization and an increase in membrane conductance. In many invertebrate
      preparations, efferent neurons that innervate mechanosensory afferents contain
      glutamate in addition to GABA, suggesting that the sensory neurons are also
      modulated by glutamate. However, the effects of glutamate on these neurons are
      not well understood. Peripheral parts of the spider (Cupiennius salei)
      mechanosensory neurons are surrounded by efferent fibers immunoreactive to
      antibodies against GABA and glutamate. GABA and its analogue muscimol were shown
      to effectively inhibit spider mechanosensory neurons innervating lyriform slit
      sensilla VS-3 that detects cuticular strains in the leg. Here, we show that
      glutamate also inhibits the VS-3 neurons, but its effects are different from
      those of GABA or muscimol, suggesting that it acts on a different group of
      receptors. GABA and muscimol always depolarized these neurons and the inhibitory
      effect was strongly correlated with the amount of depolarization. In contrast,
      glutamate inhibited the VS-3 neurons even when it did not depolarize them. In
      addition, while glutamate inhibited both the axonal action potentials elicited
      with electrical stimulation and dendritic action potentials produced by
      mechanical stimulation, muscimol only inhibited the axonal action potentials.
      Therefore, the inhibitory glutamate receptors in the VS-3 neurons are distinct
      from and differently distributed than the GABA receptors, providing a subtle
      control of the neurons' sensitivity in varying behavioural situations.

PMID- 16101746
TI  - Spatio-temporal Ca2+ dynamics of moth olfactory projection neurones.
AB  - We studied the Ca2+ dynamics of odour-evoked glomerular patterns in the antennal
      lobe of the moth Spodoptera littoralis using optical imaging. Here we selectively
      stained a large population of antennal lobe output neurones, projection neurones,
      by retrograde filling with FURA-dextran from the inner antennocerebral tract in
      the protocerebrum. Different plant-associated odorants evoked distributed
      patterns of activated glomeruli that were odour dependent and repeatable. These
      patterns were, however, dynamic during the period of odour exposure. Temporal
      responses differed across glomeruli and were stimulus dependent. Next we examined
      how the correlations between patterns evoked by different odorants changed with
      time. Initially, responses to structurally similar compounds were highly
      correlated, whereas responses to structurally different compounds differed.
      Within the period of odour exposure (1 s) we found a significant reduction in
      similarity of responses evoked by different odours, irrespective of initial
      similarity, whereas trial-to-trial correlations remained high. Our results
      suggested an ability for coarse classification at the initial encounter with an
      odour source. With time, however, the discrimination ability increases and
      structurally similar odours can be distinguished.

PMID- 16101747
TI  - In vivo characterization of the angiotensin-(1-7)-induced dopamine and gamma
      aminobutyric acid release in the striatum of the rat.
AB  - The effect of angiotensin (Ang)-1-7 on dopamine, gamma-aminobutyric acid (GABA)
      and glutamate release in the striatum of the rat was examined using in vivo
      microdialysis. Ang-(1-7) was administered locally in the striatum through the
      microdialysis probe. At a concentration of 100 microm, Ang-(1-7) caused a
      significant increase in extracellular dopamine and GABA but had no effect on
      glutamate release. The Ang-(1-7)-induced dopamine release was blocked by EC33, an
      inhibitor of aminopeptidase A, an enzyme which converts Ang-(1-7) into Ang-(3-7),
      suggesting that this effect occurs after metabolism into Ang-(3-7). Indeed,
      administration of Ang-(3-7) (10-100 microm) into the striatum caused a more
      potent increase in the striatal dopamine release than Ang-(1-7). Because Ang-(3
      7) is an inhibitor of insulin-regulated aminopeptidase (IRAP) and because Ang IV,
      another IRAP inhibitor, also causes a concentration-dependent increase in
      dopamine in the rat striatum, IRAP may be involved in this effect. In contrast,
      EC33 had no effect on the Ang-(1-7)-induced GABA increase but the GABA release
      was blocked by the putative AT(1-7) receptor antagonist A779 (0.1 microm) and by
      the nitric oxide synthase inhibitor L-NAME (1 mm). These drugs could not block
      the effect of Ang-(1-7) on the striatal dopamine release suggesting that only the
      observed effects on GABA release are mediated by the AT(1-7) receptor and/or are
      associated with a release of nitric oxide.

PMID- 16101748
TI  - Nerve growth factor-induced circadian phase shifts and MAP kinase activation in
      the hamster suprachiasmatic nuclei.
AB  - Circadian rhythms are entrained by light and by several neurochemical stimuli. In
      hamsters housed in constant darkness, i.c.v. administration of nerve growth
      factor (NGF) at various times in their circadian cycle produced phase shifts of
      locomotor activity rhythms that were similar in direction and circadian timing to
      those produced by brief pulses of light. Moreover, the effect of NGF and light
      were not additive, indicating signalling points in common. These points include
      the immediate-early gene c-fos and ERK1/2, a component of the mitogen-activated
      protein kinases (MAPK) family. NGF activates c-FOS and ERK1/2-MAPK in the
      suprachiasmatic nuclei, the site of a circadian clock in mammals, when
      administered during the subjective night but not during the day. The effect of
      NGF on ERK1/2 activation was not inhibited by the administration of MK-801, a
      glutamate/NMDA receptor antagonist. These results suggest that NGF, acting
      through MAPK activation, plays a role in photic entrainment of the mammalian
      circadian clock.

PMID- 16101749
TI  - Up-regulation of VGLUT2 expression in hypothalamic-neurohypophysial neurons of
      the rat following osmotic challenge.
AB  - A second vesicular glutamate transporter (VGLUT2) has been reported to be
      expressed in neurosecretory neurons of the hypothalamic-neurohypophysial system.
      To study its role in the neurosecretory neurons, we evaluated the expression of
      the VGLUT2 gene in the paraventricular (PVN) and supraoptic (SON) nuclei as well
      as the immunoreactivity in the neurohypophysis under euhydrated and chronic
      hyperosmotic conditions with in situ hybridization and immunohistochemistry. The
      intensity of hybridization signals in the PVN, SON and thalamus of rats subjected
      to water deprivation for 7 days, or drinking 2% NaCl for 4 or 7 days, was
      compared with that of euhydrated rats (control). The overall intensity in the
      entire PVN or SON, but not the thalamus, was higher in osmotically stimulated
      rats than in controls. Within the PVN, a significantly higher intensity of
      signals than that of controls was found only in the dorsolateral posterior
      magnocellular region in 4-day salt-loaded rats and in all subregions in water
      deprived or 7-day salt-loaded rats. The intensity in the SON was higher in the
      stimulated rats than in controls, regardless of subregions. In the
      neurohypophysis, VGLUT2 staining was frequently localized in vasopressin
      terminals of control rats and was apparently reduced in stimulated rats. These
      results indicate that VGLUT2 is principally expressed in magnocellular
      vasopressin neurons, suggesting some local effect of intrinsic glutamate on
      neurohypophysial hormone secretion.

PMID- 16101750
TI  - Graded classes of cortical connections: quantitative analyses of laminar
      projections to motion areas of cat extrastriate cortex.
AB  - Current hierarchical models of the cerebral cortex are mainly based on
      qualitative connection studies. From wheatgerm-agglutinin-horseradish peroxidase
      injections, we examined the laminar patterns of projections to and between the
      three major subdivisions of the motion-processing lateral suprasylvian (LS)
      complex [areas posteromedial lateral suprasylvian area (PMLS), anteromedial
      lateral suprasylvian (AMLS), posterolateral lateral suprasylvian area (PLLS)] of
      cat extrastriate cortex and of an adjoining form-processing area, 21a. We counted
      approximately 145,000 labelled projection cells in 20 cortical areas in 11 cats,
      and applied various analyses to the data, expressed as the percent supragranular
      layer (%SG) origin of each connection. We report two main results. (i) A wide
      range of %SG values was obtained, both from each individual cat and across the
      163 projections examined. Nonetheless, both hierarchical and non-parametric
      cluster analyses of the pooled connection origins suggested the presence of three
      distinct laminar projection classes, constrained by graded %SG values of 0-33%,
      39-69% and 76-97%. These conformed, respectively, to feedback, lateral and
      feedforward laminar patterns seen qualitatively in our material. (ii)
      Hierarchical connectivity analyses suggested that PMLS, AMLS and PLLS are ordered
      in a hierarchical sequence. Macaque motion areas V5/MT, MST and FST are arranged
      in a similar sequence, and areas at equivalent levels of the two motion
      hierarchies have some analogous functional specializations. Our findings provide
      the first objective support for the three laminar projection classes that
      underpin existing theoretical models of hierarchical cortical organization, and
      they suggest that the implementation of higher-order motion processing evolved
      along similar lines in the cat and monkey visual cortex.

PMID- 16101751
TI  - Differential effects of calcineurin inhibition and protein kinase A activation on
      nucleus accumbens amphetamine-produced conditioned place preference in rats.
AB  - The nucleus accumbens (NAc) plays a critical role in amphetamine-produced
      conditioned place preference (CPP). In previous studies inhibition or activation
      of cyclic adenosine monophosphate-dependent protein kinase (PKA) blocked NAc
      amphetamine-produced CPP. PKA activation unrelated to ongoing DA transmission may
      disrupt reward-related learning. Calcineurin (CN) down-regulates downstream PKA
      targets. Unlike PKA activation, CN inhibition may preserve and enhance reward
      related learning. The PKA signalling cascade is negatively regulated by
      calcineurin (CN). We tested the hypothesis that post-training CN inhibition in
      NAc will enhance NAc amphetamine-produced CPP and that PKA activation will block
      CPP. Eight but not four or two 30-min conditioning sessions were sufficient to
      establish significant CPP. Immediate post-training, NAc injection of the
      calcineurin inhibitor FK506 (5.0 but not 1.0 microg in 0.5 microL per side) led
      to a significant amphetamine CPP in rats receiving four but not two training
      sessions; the 5.0-microg dose had no effect on rats trained with eight sessions.
      Injections of the PKA activator Sp-cAMPS (2.5 or 10.0 microg in 0.5 microL per
      side) failed to affect CPP following two or four training sessions and blocked
      CPP produced by a standard 8-day conditioning schedule. Results suggest that CN
      acts as a negative regulator in the establishment of NAc amphetamine-produced
      CPP, a form of reward-related learning.

PMID- 16101752
TI  - The anterior ectosylvian visual area of the ferret: a homologue for an enigmatic
      visual cortical area of the cat?
AB  - The present paper describes the results of electrophysiological mapping
      experiments focused on the anterior limb of the ectosylvian gyrus of the ferret
      (Mustela putorius). The aim was to determine if the ferret possessed a homologous
      cortical area to the anterior ectosylvian visual area (AEV) of the domestic cat,
      but not clearly delineated in any other mammal studied to date. We were able to
      gather data on the visuotopic organization of a region that we consider to be a
      homologue of cat AEV. The visual map in this area showed a distinct visuotopic
      organization and covered a large extent of the visual field. Within the ferret
      AEV there were clusters of bimodal recording sites (somato-visual and audio
      visual) that were located adjacent to surrounding unimodal cortical areas (such
      as the second somatosensory area and primary and secondary auditory areas). The
      ferret AEV, like that of the cat, was topographically isolated from other visual
      cortical areas by intervening auditory and somatosensory areas. Taken together
      these features suggest that the region described here as AEV in the ferret is
      indeed a direct homologue of the previously described cat AEV.

PMID- 16101753
TI  - Transcriptional involvement of protein kinase C-alpha isozyme in amphetamine
      mediated appetite suppression.
AB  - Amphetamine (AMPH) is known as an anorectic agent. The anorectic action of AMPH
      has been attributed to its inhibitory action on hypothalamic neuropeptide Y
      (NPY), an appetite stimulant in the brain. The molecular mechanisms behind this
      anorectic action of AMPH are still unclear. This study investigated the possible
      role of protein kinase C (PKC) isotypes in this anorectic action. Results
      revealed that most PKC isotypes (alpha, betaII, gamma, delta, eta, lambda and
      zeta), except betaI and epsilon isotypes, were stimulated during a repeated
      treatment of AMPH. Among these stimulated isotypes, three isotypes (alpha, delta,
      lambda) were activated and expressed in a similar manner, while the other
      isotypes were expressed differently and specifically. To determine if PKCalpha
      was involved in the anorectic response of AMPH, the infusions of antisense
      oligonucleotide into the brain were performed 1 h before daily AMPH treatment in
      freely moving rats, and the results showed that PKCalpha knock down could block
      the anorectic response and restore NPY mRNA levels in AMPH-treated rats. These
      results suggest that PKC isotypes- (at least the alpha isotype), related
      modification of NPY gene expression in hypothalamus might play an essential role
      in the central regulation of AMPH-mediated feeding suppression.

PMID- 16101754
TI  - Individual differences in male rat ejaculatory behaviour: searching for models to
      study ejaculation disorders.
AB  - In addition to investigating sexual function in rats that display normal
      ejaculatory behaviour, studying rats that are either 'hyposexual' or
      'hypersexual' may provide important insights into the aetiology of ejaculatory
      dysfunctions in men, such as premature and retarded ejaculation. To this end,
      rats were matched into groups of 'sluggish', 'normal' and 'rapid' ejaculators
      based on their ejaculation frequencies displayed in a series of weekly sexual
      behaviour tests. Selecting rats on this parameter revealed large and stable
      differences in other parameters of sexual behaviour as well, including
      ejaculation latency and mount frequency but not intromission frequency and mount
      latency, putative indices of sexual motivation. Neuroanatomically, Fos
      immunoreactivity as a measure of neuronal activation was increased in rapid
      ejaculators compared with sluggish ejaculators in ejaculation-related brain
      areas, presumably associated with the differences in ejaculatory behaviour.
      Although the total number of oxytocin neurones within subregions of the
      hypothalamus did not differ between groups, in the supraoptic nucleus of the
      hypothalamus more oxytocin neurones were activated in rapid ejaculators compared
      with the other groups. Apart from the differences observed in ejaculatory
      behaviour, groups did not differ with respect to their locomotor activity and
      approach-avoidance behaviour as measured in the elevated plus-maze. Finally,
      apomorphine-induced stereotypy was similar in sluggish and rapid ejaculators,
      suggesting no large differences in dopamine susceptibility. Altogether, the
      present results suggest stable differences in male rat ejaculatory behaviour.
      Further exploring the neurobiological mechanisms underlying these differences may
      be a promising approach to gain insights into the aetiology of sexual
      dysfunctions such as premature, retarded or an-ejaculation.

PMID- 16101755
TI  - The unilateral 6-OHDA rat model of Parkinson's disease revisited: an
      electromyographic and behavioural analysis.
AB  - The characteristic locomotor disturbances of Parkinson's disease (PD) include
      shuffling gait, short steps and low walking velocity. In this study we
      investigated features of walking and turning in a rat model of PD caused by
      unilateral infusion of the neurotoxin 6-hydroxydopamine (6-OHDA). We assessed
      gait and electromyographic (EMG) patterns of the ankle flexor tibialis anterior
      and the knee extensor vastus lateralis of the hindlimb, and triceps brachii of
      the forelimb, during overground locomotion, spontaneous rotation (turning) and
      apomorphine-induced rotation. When compared with control rats, rats with
      unilateral dopamine depletion displayed a shuffling gait and short stride
      lengths. This locomotor pattern was accompanied by prolonged ankle flexor
      activity on the ipsilateral side, and prolonged activity of knee extensors on the
      contralateral side. The dopamine depletion also led to enhanced contraversive
      rotations after an apomorphine challenge. The EMG recordings during drug-induced
      rotation suggested that hindlimb stepping was a reflective response to an active
      drive produced by forelimbs. The EMG recordings of the contralateral side during
      rotation were marked by reduced ankle flexor activity and increased knee extensor
      activity. Furthermore, EMG recordings indicated that dopamine-agonists induce
      rotational bias by altering the coupling between ipsi- and contralateral
      hindlimbs, and between forelimbs. In straight walking, however, the gait of 6
      OHDA lesion animals reflected normal, coupled hindlimb stepping as controlled by
      spinal pattern generators. The data suggest that the unilateral rat model of PD
      resembles key features of human parkinsonian gait, and that asymmetric descending
      input may underlie the observed changes in gait patterns.

PMID- 16101756
TI  - Spatial learning with unilateral and bilateral hippocampal networks.
AB  - This study investigated the ability of animals to learn both reference memory and
      delayed matching-to-place variants of the watermaze after large lesions of the
      hippocampus that deliberately spared only small remnants of the structure. Groups
      were created that had differing blocks of residual tissue in the septal pole of
      the hippocampus (15% or 30% of total volume), located either unilaterally (30 or
      50% on one side, 0% on the other) or bilaterally (30 + 30%). These groups were
      capable of learning the reference memory task, as indexed by normal spatially
      focused searching in a probe trial, but their rate of learning was slower than
      that of sham-lesioned rats. An impairment in the rate of learning was also seen
      in the delayed match-to-place task, where one-trial memory was observed only at
      the shortest (5 s) intertrial interval in the lesioned groups with the largest
      sparing. In both tasks performance was proportional to the volume of hippocampus
      spared and independent of whether this was unilaterally or bilaterally located.
      The findings are compatible with distributed processing accounts of hippocampal
      memory storage.

PMID- 16101757
TI  - Requirement of NMDA receptor reactivation for consolidation and storage of
      nondeclarative taste memory revealed by inducible NR1 knockout.
AB  - We employed an inducible, reversible and region-specific gene knockout technique
      to investigate the requirements for cortical NMDA receptors (NMDAR) during the
      various stages (acquisition, consolidation and storage, and retrieval) of
      nondeclarative, hippocampal-independent memory in mice using a conditioned taste
      aversion memory paradigm. Here we show that temporary knockout of the cortical
      NMDAR during either the learning or postlearning consolidation stage, but not
      during the retrieval stage, causes severe performance deficits in the 1-month
      taste memory retention tests. More importantly, we found that the consolidation
      and storage of the long-term nondeclarative taste memories requires cortical
      NMDAR reactivation. Thus, the dynamic engagement of the NMDAR during the
      postlearning stage leads us to postulate that NMDAR reactivation-mediated
      synaptic re-entry reinforcement is crucial for overcoming the destabilizing
      effects intrinsic to synaptic protein turnover and for achieving consolidation
      and storage of nondeclarative memories in the brain.

PMID- 16101758
TI  - The role of the medial temporal lobe in autistic spectrum disorders.
AB  - The neural basis of autistic spectrum disorders (ASDs) is poorly understood.
      Studies of mnemonic function in ASD suggest a profile of impaired episodic memory
      with relative preservation of semantic memory (at least in high-functioning
      individuals). Such a pattern is consistent with developmental hippocampal
      abnormality. However, imaging evidence for abnormality of the hippocampal
      formation in ASD is inconsistent. These inconsistencies led us to examine the
      memory profile of children with ASD and the relationship to structural
      abnormalities. A cohort of high-functioning individuals with ASD and matched
      controls completed a comprehensive neuropsychological memory battery and
      underwent magnetic resonance imaging for the purpose of voxel-based morphometric
      analyses. Correlations between cognitive/behavioural test scores and quantified
      results of brain scans were also carried out to further examine the role of the
      medial temporal lobe in ASD. A selective deficit in episodic memory with relative
      preservation of semantic memory was found. Voxel-based morphometry revealed
      bilateral abnormalities in several areas implicated in ASD including the
      hippocampal formation. A significant correlation was found between parental
      ratings reflecting autistic symptomatology and the measure of grey matter density
      in the junction area involving the amygdala, hippocampus and entorhinal cortex.
      The data reveal a pattern of impaired and relatively preserved mnemonic function
      that is consistent with a hippocampal abnormality of developmental origin. The
      structural imaging data highlight abnormalities in several brain regions
      previously implicated in ASD, including the medial temporal lobes.

PMID- 16101759
TI  - Viewing the body prepares the brain for touch: effects of TMS over somatosensory
      cortex.
AB  - Viewing the body can improve tactile perception. We investigated whether this
      could be due to a remodeling of somatosensory cortical areas during vision of the
      body. Single-pulse transcranial magnetic stimulation (TMS) was delivered over the
      primary and secondary somatosensory areas of subjects who showed clear visual
      tactile enhancement while they performed a tactile grating discrimination task.
      Before the tactile stimulus, subjects viewed either their right index finger
      through a semisilvered mirror or an object reflected by the mirror and positioned
      to appear in the same location as the finger. In a first experiment we observed
      that TMS over primary somatosensory cortex significantly reduced subjects'
      accuracy whilst viewing the hand. No such reduction was found when subjects
      viewed a neutral object. In a second experiment, we disrupted the activity of
      primary and secondary somatosensory areas in different sessions. When stimulating
      the primary somatosensory cortex, a reduction in accuracy was again found while
      viewing the hand, but not a neutral object. TMS over secondary somatosensory
      cortex had no effect in any condition. Our results show that vision of the body
      may act at an early stage in stimulus elaboration and perception, allowing an
      anticipatory tuning of the neural circuits in primary somatosensory cortex that
      underlie tactile acuity.

PMID- 16101760
TI  - Methylazoxymethanol acetate does not fully block cell genesis in the young and
      aged dentate gyrus.
AB  - During adulthood, new neurons are continuously added to the mammalian dentate
      gyrus (DG). An increasing number of studies have correlated changes in rates of
      dentate neurogenesis with memory abilities. One study based on subchronic
      treatment with the toxin methylazoxymethanol acetate (MAM) has provided causal
      evidence that neurogenesis is involved in hippocampal-dependent trace
      conditioning. In contrast, spatial learning is not impaired following MAM
      treatment. We hypothesized that this was due to the small residual number of new
      cells produced following MAM treatment. In the present experiment, we attempted
      to achieve a higher level of reduction of adult-generated cells following MAM
      treatment in young and aged rats. We found only a partial reduction of adult
      generated cells in the DG. More importantly, independently of the age of the
      animals, MAM treatment at a dose necessary to reduce neurogenesis altered the
      overall health of the animals. In conclusion, the behavioural results obtained
      following subchronic treatment with high doses of MAM in adulthood must be
      interpreted with extreme caution.

PMID- 16101761
TI  - Ten years of AFLP in ecology and evolution: why so few animals?
AB  - Researchers in the field of molecular ecology and evolution require versatile and
      low-cost genetic typing methods. The AFLP (amplified fragment length
      polymorphism) method was introduced 10 years ago and shows many features that
      fulfil these requirements. With good quality genomic DNA at hand, it is
      relatively easy to generate anonymous multilocus DNA profiles in most species and
      the start-up time before data can be generated is often less than a week. Built
      in dynamic, yet simple modifications make it possible to find a protocol suitable
      to the genome size of the species and to screen thousands of loci in hundreds of
      individuals for a relatively low cost. Until now, the method has primarily been
      applied in studies of plants, bacteria and fungi, with a strong bias towards
      economically important cultivated species and their pests. In this review we
      identify a number of research areas in the study of wild species of animals where
      the AFLP method, presently very much underused, should be a very valuable tool.
      These aspects include classical problems such as studies of population genetic
      structure and phylogenetic reconstructions, and also new challenges such as
      finding markers for genes governing adaptations in wild populations and
      modifications of the protocol that makes it possible to measure expression
      variation of multiple genes (cDNA-AFLP) and the distribution of DNA methylation.
      We hope this review will help molecular ecologists to identify when AFLP is
      likely to be superior to other more established methods, such as microsatellites,
      SNP (single nucleotide polymorphism) analyses and multigene DNA sequencing.

PMID- 16101762
TI  - Detecting past population bottlenecks using temporal genetic data.
AB  - Population bottlenecks wield a powerful influence on the evolution of species and
      populations by reducing the repertoire of responses available for stochastic
      environmental events. Although modern contractions of wild populations due to
      human-related impacts have been documented globally, discerning historic
      bottlenecks for all but the most recent and severe events remains a serious
      challenge. Genetic samples dating to different points in time may provide a
      solution in some cases. We conducted serial coalescent simulations to assess the
      extent to which temporal genetic data are informative regarding population
      bottlenecks. These simulations demonstrated that the power to reject a constant
      population size hypothesis using both ancient and modern genetic data is almost
      always higher than that based solely on modern data. The difference in power
      between the modern and temporal DNA approaches depends significantly on effective
      population size and bottleneck intensity and less significantly on sample size.
      The temporal approach provides more power in cases of genetic recovery (via
      migration) from a bottleneck than in cases of demographic recovery (via
      population growth). Choice of genetic region is critical, as mutation rate
      heavily influences the extent to which temporal sampling yields novel information
      regarding the demographic history of populations.

PMID- 16101763
TI  - Island colonization and founder effects: the invasion of the Guadeloupe islands
      by ship rats (Rattus rattus).
AB  - The stepwise colonization of islands within an archipelago is typically
      punctuated by successive founder effects, with each newly founded population
      being a subsample of the gene pool of the source island. Thus, the genetic
      signature of successive bottlenecks should be detected when analysing the genetic
      structure between islands of an archipelago. To test this prediction, we
      investigated introduced ship rat populations, Rattus rattus (Linnaeus, 1758), in
      the Guadeloupe Archipelago. Three different methods, commonly named the
      heterozygosity excess, the mode-shift indicator and the M ratio method, were used
      to detect bottlenecks from genetic data obtained with eight microsatellite
      markers on Guadeloupe and two neighbouring islands, Petite-Terre and Fajou.
      Moreover, a recent eradication failure on Fajou allowed us to test the accuracy
      of the methods in an 'experimental-like' situation. The results indicate that
      rats were introduced on Guadeloupe first, which then became the source population
      for independent secondary colonization of Fajou and Petite-Terre. Moreover, the
      heterozygosity excess and the mode-shift indicator only detected bottlenecks for
      the recent colonization of Petite-Terre and the eradication failure on Fajou.
      However, bottlenecks were detected for all the populations using the M ratio
      method. This could be interpreted as the remaining signature of the early
      introduction of the ship rat in the archipelago.

PMID- 16101764
TI  - Temporal variation of the population structure and genetic diversity of
      Farfantepenaeus notialis assessed by allozyme loci.
AB  - Population genetic studies carried out on penaeid shrimps have disclosed
      different patterns of population subdivision, revealing new aspects of shrimp
      biology as well as the effects of historical contingency molding those patterns.
      However, the stability of observed allele frequencies over time still remains
      untested. The objective of this article is to show the analysis of the temporal
      variation of allozymes in a shrimp species inhabiting Cuba which proves that the
      genetic structure of this species could significantly change in time. The study
      involves four populations of Farfantepenaeus notialis sampled in a period of 8
      years. The significant statistics obtained from partitions observed in 1995 were
      not detected in 2003 (as suggested by AMOVA and F(ST)), whereas temporal genetic
      differentiation and heterozygosity became highly significant. The results
      strongly suggest that the effect of migrations could be the cause for the loss of
      F. notialis genetic structure in 2003. It is therefore imperative to call
      attention on the vulnerability of these populations when facing unstable
      environmental and habitat conditions.

PMID- 16101765
TI  - Comparative landscape genetics and the adaptive radiation of Darwin's finches:
      the role of peripheral isolation.
AB  - We use genetic divergence at 16 microsatellite loci to investigate how
      geographical features of the Galapagos landscape structure island populations of
      Darwin's finches. We compare the three most genetically divergent groups of
      Darwin's finches comprising morphologically and ecologically similar allopatric
      populations: the cactus finches (Geospiza scandens and Geospiza conirostris), the
      sharp-beaked ground finches (Geospiza difficilis) and the warbler finches
      (Certhidea olivacea and Certhidea fusca). Evidence of reduced genetic diversity
      due to drift was limited to warbler finches on small, peripheral islands.
      Evidence of low levels of recent interisland migration was widespread throughout
      all three groups. The hypothesis of distance-limited dispersal received the
      strongest support in cactus and sharp-beaked ground finches as evidenced by
      patterns of isolation by distance, while warbler finches showed a weaker
      relationship. Support for the hypothesis that gene flow constrains morphological
      divergence was only found in one of eight comparisons within these groups. Among
      warbler finches, genetic divergence was relatively high while phenotypic
      divergence was low, implicating stabilizing selection rather than constraint due
      to gene flow. We conclude that the adaptive radiation of Darwin's finches has
      occurred in the presence of ongoing but low levels of gene flow caused by
      distance-dependent interisland dispersal. Gene flow does not constrain phenotypic
      divergence, but may augment genetic variation and facilitate evolution due to
      natural selection. Both microsatellites and mtDNA agree in that subsets of
      peripheral populations of two older groups are genetically more similar to other
      species that underwent dramatic morphological change. The apparent decoupling of
      morphological and molecular evolution may be accounted for by a modification of
      Lack's two-stage model of speciation: relative ecological stasis in allopatry
      followed by secondary contact, ecological interactions and asymmetric phenotypic
      divergence.

PMID- 16101766
TI  - Using naturally shed feathers for individual identification, genetic parentage
      analyses, and population monitoring in an endangered Eastern imperial eagle
      (Aquila heliaca) population from Kazakhstan.
AB  - Genetic analyses on noninvasively collected samples have revolutionized how
      populations are monitored. Most noninvasive monitoring studies have used hair or
      scat for individual identification of elusive mammals, but here we utilize
      naturally shed feathers. The Eastern imperial eagle (EIE) is a species of
      conservation concern throughout Central Asia and, like most raptors, EIEs are
      inherently challenging to study because adults are difficult to capture and band
      using conventional techniques. Over 6 years, we noninvasively collected hundreds
      of adult feathers and directly sampled EIE chicks at a national nature reserve in
      Kazakhstan. All samples were genetically sexed and genotyped at a suite of
      microsatellite loci. Genetically profiled adult feathers identified and monitored
      the presence of individual eagles over time, enabling us to address a variety of
      issues related to the biology, demography, and conservation of EIEs.
      Specifically, we characterized (i) the genetic mating system, (ii) relatedness
      among mated pairs, (iii) chick sex ratios, and (iv) annual turnover in an adult
      breeding population. We show that EIEs are genetically monogamous and
      furthermore, there is no apparent relatedness-based system of mate choice (e.g.
      inbreeding avoidance). Results indicate that annual adult EIE survivorship (84%)
      is lower than expected for a long-lived raptor, but initial analyses suggest the
      current reproductive rate at our study site is sufficient to maintain a stable
      breeding population. The pristine habitat at our study site supports an EIE
      population that is probably the most demographically robust in the world; thus,
      our results caution that populations in marginal habitats may not be self
      sustaining.

PMID- 16101767
TI  - Clonal and spatial genetic structures of aspen (Populus tremuloides Michx.).
AB  - To portray aspen clonal and spatial genetic structures, we mapped and genotyped
      trees in two 1-ha plots, each containing three aspen cohorts originating from
      fire or subsequent secondary disturbances. We used four microsatellite loci to
      identify aspen clones and increment core analysis to determine tree age. Clonal
      dimensions were measured by the maximum distance between two ramets and the
      number of ramets per genet. Standard normal deviate (SND) was used to assess the
      spatial distribution of aspen genets and cohorts, and multivariate spatial
      genetic autocorrelations to assess the spatial distribution of aspen genetic
      variation. Most aspen genets consisted of only one ramet (> 75%). Median clonal
      dimensions were 19 and 29 m (maxima: 104 and 72 m in the two plots). No
      segregation was observed between clones. Aspen cohorts were spatially segregated
      but trees were spatially aggregated within old and medium-aged cohorts. In
      contrast, trees were more randomly distributed within the youngest cohorts. This
      coincided with a spatial genetic autocorrelation at small scales (up to 30 m) in
      the older cohorts and a more random genetic distribution in the youngest ones.
      Our results suggest that aspen spatial genetic structuring reflects the spatial
      patterns produced by the regeneration of discrete cohorts at different stages of
      succession. Vegetative reproduction leads to aspen genetic spatial structuring at
      small scales (few metres) until midsuccession. However, as the stand gets older,
      the spatial distribution of aspen trees and genetic structure evolve from a
      structured pattern to a more random one under a gap disturbances regime.

PMID- 16101768
TI  - Genetic variation and population structure in remnant populations of black
      rhinoceros, Diceros bicornis, in Africa.
AB  - Black rhinoceros (Diceros bicornis) are one of the most endangered mammal species
      in Africa, with a population decline of more than 96% by the end of the last
      century. Habitat destruction and encroachment has resulted in fragmentation of
      the remaining populations. To assist in conservation management, baseline
      information is provided here on relative genetic diversity and population
      differentiation among the four remaining recognized subspecies. Using
      microsatellite data from nine loci and 121 black rhinoceros individuals, and
      comparing the results with those of other African species affected in similar
      ways, Diceros bicornis michaeli retained the most genetic diversity
      (heterozygosity 0.675) compared with Diceros bicornis minor (0.459) and Diceros
      bicornis bicornis (0.505), suggesting that the duration of the known bottlenecks
      in these populations has only had a limited impact on diversity. Comparable and
      moderate degrees of population differentiation were found between D. b. minor, D.
      b. bicornis and D. b. michaeli. Results from the single sample available of the
      most endangered subspecies, Diceros bicornis longipes, showed the least diversity
      of all individuals examined. This information should assist conservation
      management decisions, especially those affecting population viability assessments
      and selection of individuals for translocations, and will also facilitate
      subspecies identification for ex situ individuals of uncertain origin.

PMID- 16101769
TI  - Ice age cloning--comparison of the Quaternary evolutionary histories of sexual
      and clonal forms of spiny loaches (Cobitis; Teleostei) using the analysis of
      mitochondrial DNA variation.
AB  - Recent advances in population history reconstruction offered a powerful tool for
      comparisons of the abilities of sexual and clonal forms to respond to Quaternary
      climatic oscillations, ultimately leading to inferences about the advantages and
      disadvantages of a given mode of reproduction. We reconstructed the Quaternary
      historical biogeography of the sexual parental species and clonal hybrid lineages
      within the Europe-wide hybrid complex of Cobitis spiny loaches. Cobitis
      elongatoides and Cobitis taenia recolonizing Europe from separated refuges met in
      central Europe and the Pontic region giving rise to hybrid lineages during the
      Holocene. Cobitis elongatoides due to its long-term reproductive contact with the
      remaining parental species of the complex--C. tanaitica and C. spec.--gave rise
      to two clonal hybrid lineages probably during the last interglacial or even
      earlier, which survived the Wurmian glaciation with C. elongatoides. These
      lineages followed C. elongatoides postglacial expansion and probably decreased
      its dispersal rate. Our data indicate the frequent origins of asexuality
      irrespective of the parental populations involved and the comparable dispersal
      potential of diploid and triploid lineages.

PMID- 16101770
TI  - Hares on ice: phylogeography and historical demographics of Lepus arcticus, L.
      othus, and L. timidus (Mammalia: Lagomorpha).
AB  - Phylogeographical investigations of arctic organisms provide spatial and temporal
      frameworks for interpreting the role of climate change on biotic diversity in
      high-latitude ecosystems. Phylogenetic analyses were conducted on 473 base pairs
      of the mitochondrial control region in 192 arctic hares (Lepus arcticus, Lepus
      othus, Lepus timidus) and two individual Lepus townsendii. The three arctic hare
      species are closely related. All L. othus individuals form one well-supported
      clade, L. arcticus individuals form two well-supported clades, and L. timidus
      individuals are scattered throughout the phylogeny. Arctic hare distribution was
      altered dramatically following post-Pleistocene recession of continental ice
      sheets. We tested for genetic signatures of population expansion for hare
      populations now found in deglaciated areas. Historical demographic estimates for
      12 arctic hare populations from throughout their range indicate that L. arcticus
      and L. othus persisted in two separate North American arctic refugia (Beringia
      and High Canadian Arctic) during glacial advances of the Pleistocene, while the
      high genetic diversity in L. timidus likely reflects multiple Eurasian refugia.

PMID- 16101771
TI  - Phylogeography and demography of Guianan harlequin toads (Atelopus):
      diversification within a refuge.
AB  - We investigated the genetic structure of populations of Guianan harlequin toads
      (genus Atelopus) and their evolutionary affinities to extra-Guianan congeners.
      Phylogenetic analysis of mitochondrial cytochrome b (cyt b) and NADH
      dehydrogenase subunit 2 (ND2) gene sequences produced well-supported clades
      largely corresponding to the four recognized taxa in the Guianas (Atelopus
      spumarius hoogmoedi, Atelopus spumarius barbotini, Atelopus franciscus, and
      Atelopus flavescens). Our findings suggest that the Guianan A. spumarius
      represent distinct evolutionary lineages that merit distinction from Amazonian
      conspecifics, and that the status of A. flavescens and A. franciscus is somewhat
      less clear. Approximately 69% of the observed genetic variation is accounted for
      by differences between these four recognized taxa. Coalescent-based estimates of
      gene flow between taxa suggest that these lineages are largely isolated from one
      another. Negligible rates of migration between populations and significant
      divergence within such close proximity suggests that although the region
      inhabited by these taxa is almost entirely undisturbed, significant habitat
      heterogeneity exists as to have produced a remarkable diversification of Atelopus
      within the eastern Guiana Shield. These results contradict the commonly held view
      of the Guiana Shield as a 'refuge' whose stability during late Tertiary and
      Quaternary climatic fluctuations served as a biotic reservoir. Instead, we
      provide evidence that climatic fluctuations during this time had a diversifying
      effect within the Guianan region.

PMID- 16101772
TI  - Cryptic Neogene vicariance and Quaternary dispersal of the red-spotted toad (Bufo
      punctatus): insights on the evolution of North American warm desert biotas.
AB  - We define the geographical distributions of mitochondrial DNA (mtDNA) lineages
      embedded within a broadly distributed, arid-dwelling toad, Bufo punctatus. These
      patterns were evaluated as they relate to hypothesized vicariant events leading
      to the formation of desert biotas within western North America. We assessed mtDNA
      sequence variation among 191 samples from 82 sites located throughout much of the
      species' range. Parsimony-based haplotype networks of major identified lineages
      were used in nested clade analysis (NCA) to further elucidate and evaluate
      shallow phylogeographic patterns potentially associated with Quaternary
      (Pleistocene-Holocene) vicariance and dispersal. Phylogenetic analyses provided
      strong support for three monophyletic lineages (clades) within B. punctatus. The
      geographical distributions of the clades showed little overlap and corresponded
      to the general boundaries of the Peninsular Desert, and two continental desert
      regions, Eastern (Chihuahuan Desert-Colorado Plateau) and Western (Mojave-Sonoran
      deserts), geographically separated along the Rocky Mountains and Sierra Madre
      Occidental. The observed divergence levels and congruence with postulated events
      in earth history implicate a late Neogene (latest Miocene-early Pliocene) time
      frame for separation of the major mtDNA lineages. Evaluation of nucleotide and
      haplotype diversity and interpretations from NCA reveal that populations on the
      Colorado Plateau resulted from a recent, likely post-Pleistocene, range expansion
      from the Chihuahuan Desert. Dispersal across historical barriers separating major
      continental clades appear to be recent, resulting in secondary contacts in at
      least two areas. Given the observed contact between major clades, we speculated
      as to why the observed deep phylogeographic structure has not been eroded during
      the multiple previous interglacials of the Pleistocene.

PMID- 16101773
TI  - Phylogeography of the longhorn cactus beetle Moneilema appressum LeConte
      (Coleoptera: Cerambycidae): was the differentiation of the Madrean sky islands
      driven by Pleistocene climate changes?
AB  - Although it has been suggested that Pleistocene climate changes drove population
      differentiation and speciation in many groups of organisms, population genetic
      evidence in support of this scenario has been ambiguous, and it has often been
      difficult to distinguish putative vicariance from simple isolation by distance.
      The sky island communities of the American Southwest present an ideal system in
      which to compare late Pleistocene range fragmentations documented by
      palaeoenvironmental studies with population genetic data from organisms within
      these communities. In order to elucidate the impact of Pleistocene climate
      fluctuations on these environments, biogeographic patterns in the flightless
      longhorn cactus beetle, Moneilema appressum were examined using mitochondrial DNA
      sequence data. Gene tree relationships between haplotypes were inferred using
      parsimony, maximum-likelihood, and Bayesian analysis. Nested clade analysis,
      Mantel tests, and coalescent modelling were employed to examine alternative
      biogeographic scenarios, and to test the hypothesis that Pleistocene climate
      changes drove population differentiation in this species. The program mdiv was
      used to estimate migration and divergence times between populations, and to
      measure the statistical support for isolation over ongoing migration. These
      analyses showed significant geographic structure in genetic relationships, and
      implicated topography as a key determinant of isolation. However, although the
      coalescent analyses suggested that a history of past habitat fragmentation
      underlies the observed geographic patterns, the nested clade analysis indicated
      that the pattern was consistent with isolation by distance. Estimated divergence
      times indicated that range fragmentation in M. appressum is considerably older
      than the end of the most recent glacial, but coincided with earlier interglacial
      warming events and with documented range expansions in other, desert-dwelling
      species of Moneilema.

PMID- 16101774
TI  - Phylogeography of pollinator-specific sexually deceptive Chiloglottis taxa
      (Orchidaceae): evidence for sympatric divergence?
AB  - Divergence in sexually deceptive orchids is thought to occur through shifts in
      the attraction of specific pollinators, a process that is mediated by changes in
      the floral odours that lure sexually excited male insects. We investigated the
      origin of reproductive isolation in a sexually deceptive species complex of
      Chiloglottis R.Br. (Orchidaceae: Diurideae). Two geographically separated montane
      regions in eastern Australia were sampled, each containing sympatric pairs of
      orchid taxa presently found under the name, Chiloglottis pluricallata.
      Behavioural tests confirmed at least three distinct orchid taxa that specifically
      attract different pollinators. An artificial crossing experiment among two taxa
      from one region demonstrated their interfertility, and confirmed isolation to be
      a function of pollinator attraction. A phylogeographic analysis using amplified
      fragment length polymorphisms (AFLPs) indicated that samples from each
      geographical region are most closely related, a pattern consistent with in situ
      or sympatric divergence. However, an extensive population genetic study on two
      taxa from one region failed to entirely reject the possibility of intertaxon gene
      flow. Although clear genetic differentiation of the taxa is evident in two out of
      three sites where both grow in direct sympatry, overall, the two taxa are not
      strongly distinguished by AFLP markers. The reconstruction of a simple
      bifurcating pattern of divergence may be confounded by a combination of
      contemporary population-level processes operating within each taxon, the
      retention of ancestral polymorphism or intertaxon gene flow.

PMID- 16101775
TI  - The influence of Pleistocene glacial refugia on tawny owl genetic diversity and
      phylogeography in western Europe.
AB  - The glacial refugia hypothesis indicates that during the height of the
      Pleistocene glaciations the temperate species that are today widespread in
      western Europe must have survived in small and climatically favourable areas
      located in the southern peninsulas of Iberia, Italy and Balkans. One such species
      is the tawny owl, a relatively sedentary, nonmigratory bird presently distributed
      throughout Europe. It is a tree-nesting species closely associated with deciduous
      and mixed coniferous woodlands. In this study I used control region mtDNA
      sequences from 187 individuals distributed among 14 populations to determine
      whether current genetic patterns in tawny owl populations were consistent with
      postglacial expansion from peninsular refugia. European, North African and Asian
      tawny owls were found to represent three distinct lineages, where North Africa is
      the sister clade to all European owls. Within Europe, I found three well
      supported clades that correspond to each of the three allopatric refugia.
      Expansion patterns indicate that owls from the Balkan refugium repopulated most
      of northern Europe, while expansion out of Iberia and Italy had only regional
      effects leading to admixture in France. Estimates of population divergence times
      between refugia populations are roughly similar, but one order of magnitude
      smaller between Greece and northern Europe. Based on a wide range of mutation
      rates and generation times, divergence between refugia appears to date to the
      Pleistocene.

PMID- 16101776
TI  - Mitochondrial DNA phylogeography of the Mesoamerican spiny-tailed lizards
      (Ctenosaura quinquecarinata complex): historical biogeography, species status and
      conservation.
AB  - Through the examination of past and present distributions of plants and animals,
      historical biogeographers have provided many insights on the dynamics of the
      massive organismal exchange between North and South America. However, relatively
      few phylogeographic studies have been attempted in the land bridge of Mesoamerica
      despite its importance to better understand the evolutionary forces influencing
      this biodiversity 'hotspot'. Here we use mitochondrial DNA sequence data from
      fresh samples and formalin-fixed museum specimens to investigate the genetic and
      biogeographic diversity of the threatened Mesoamerican spiny-tailed lizards of
      the Ctenosaura quinquecarinata complex. Species boundaries and their
      phylogeographic patterns are examined to better understand their disjunct
      distribution. Three monophyletic, allopatric lineages are established using mtDNA
      phylogenetic and nested clade analyses in (i) northern: Mexico, (ii) central:
      Guatemala, El Salvador and Honduras, and (iii) southern: Nicaragua and Costa
      Rica. The average sequence divergence observed between lineages varied between
      2.0% and 3.7% indicating that they do not represent a very recent split and the
      patterns of divergence support the recently established nomenclature of C.
      quinquecarinata, Ctenosaura flavidorsalis and Ctenosaura oaxacana. Considering
      the geological history of Mesoamerica and the observed phylogeographic patterns
      of these lizards, major evolutionary episodes of their radiation in Mesoamerica
      are postulated and are indicative of the regions' geological complexity. The
      implications of these findings for the historical biogeography, taxonomy and
      conservation of these lizards are discussed.

PMID- 16101777
TI  - Estimating pollen flow using SSR markers and paternity exclusion: accounting for
      mistyping.
AB  - Highly informative genetic markers, such as simple sequence repeats (SSRs), can
      be used to directly measure pollen flow by parentage analysis. However, mistyping
      (i.e. false inference of genotypes caused by the occurrence of null alleles,
      mutations, and detection errors) can lead to substantial biases in the estimates
      obtained. Using computer simulations, we evaluated a direct method for estimating
      pollen immigration using SSR markers and a paternity exclusion approach. This
      method accounts for mistyping and does not rely on assumptions about the
      distribution of male reproductive success. If ignored, even minor rates of
      mistyping (1.5%) resulted in overestimating pollen immigration by up to 150%.
      When we required at least two mismatching loci before excluding candidate fathers
      from paternity, the resulting pollen immigration estimates had small biases for
      rates of mistyping up to 4.5%. Requiring at least three mismatches for exclusion
      was needed to minimize the upward biases of pollen immigration caused by rates of
      mistyping up to 10.5%. The minimum number of highly variable SSR loci needed to
      minimize cryptic gene flow and obtain reliable estimates of pollen immigration
      varied from five to seven for a sampling scheme applicable to most conifers (i.e.
      when paternal haplotypes can be unambiguously determined). Between five and nine
      highly variable SSR loci were needed for a more general sampling scheme that is
      applicable to all diploid seed plants. With moderately variable SSR markers,
      consistently accurate estimates of pollen immigration could be obtained only for
      rates of mistyping up to 4.5%. We developed the POLLEN FLOW (PFL) computer
      program which can be used to obtain unbiased and precise estimates of pollen
      immigration under a wide range of conditions, including population sizes as large
      as 600 parents and mistyping rates as high as 10.5%.

PMID- 16101778
TI  - Control of body size of Lasius niger ant sexuals--worker interests, genes and
      environment.
AB  - In most animals, the survival and reproductive success of males and females is
      linked to their size. The ability of individuals to control environmental
      influences on size will therefore have consequences for their fitness. In
      eusocial insects, individual males and reproductive females do not have to forage
      for themselves or control their local environment. Instead, they are reared by
      nonreproductive siblings (workers) inside colonies. Workers should benefit from
      controlling the size of sexuals because these sexuals are usually the only means
      for workers to transmit their genes to future generations. Nevertheless,
      considerable intraspecific variation exists around mean sexual size in social
      hymenopterans, even in species with monomorphic sexuals. This variation could
      result from genetic influences on sexual size, for instance sexuals may be
      selected to not agree to worker interests, or be due to strong, unpredictable
      environmental conditions constraining the efforts of workers to control sexual
      size. In a study that is the first of its kind I investigated genetic and
      environmental components of sexual body size variation in the ant Lasius niger,
      examining sexuals from wild colonies with one or several fathers (paternity
      levels established through microsatellite DNA offspring analysis). Evidence was
      found for a genetic component of size (broad-sense heritability of up to 42%) but
      strong common-colony effects (among-colony variation in food availability or in
      worker capacities to restrain sexual selfishness) also increased the size
      differences among colonies. Workers thus seem to only have partial-control over
      sexual size, but may be doing the best of a bad job.

PMID- 16101779
TI  - Migratory charr schools exhibit population and kin associations beyond juvenile
      stages.
AB  - Few studies have critically investigated the genetic composition of wild fish
      schools. Yet, such investigations may have profound implications for the
      understanding of social organization and population differentiation in both
      fundamental and applied research. Using 20 microsatellite loci, we investigated
      the composition of 53 schools (total n = 211) of adult and subadult migratory
      brook charr (Salvelinus fontinalis) sampled from the known feeding areas of two
      populations inhabiting Mistassini Lake (Quebec, Canada). We specifically tested
      whether (i) school members originated from the same population, (ii) individuals
      from the same population within schools were kin (half- or full-siblings), and
      (iii) kin schooling relationships differed between sexes. Randomization tests
      revealed a tendency for most schools to be population specific, although some
      schools were population mixtures. Significantly more kin were found within
      schools than expected at random for both populations (approximately 21-34% of the
      total number of school members). This result, combined with the observed size
      range of individuals, indicated that stable associations between kin may occur
      beyond juvenile stages for up to 4 years. Nevertheless, a high proportion of
      school members were non-kin (approximately 66-79%). No differences were detected
      between sexes in the propensity to school with kin. We discuss the hypothesis
      that the stable kin groups, rather than arising from kin selection, may instead
      be a by-product of familiarity based on individual selection for the maintenance
      of local adaptations related to migration (natal and feeding area philopatry).
      Our results are noteworthy because they suggest that there is some degree of
      permanence in the composition of wild fish schools. Additionally, they support
      the hypothesis that schools can be hierarchically structured (from population
      members down to family groups) and are thus nonrandom genetic entities.

PMID- 16101780
TI  - Age-specific mating strategies and reproductive senescence.
AB  - While males gain obvious direct advantages from multiple mating, the reproductive
      capacity of females is more constrained. The reason why polyandry evolved in
      females is therefore open to many conjectures. One hypothesis postulates that
      females gain indirect benefits by increasing the probability of siring young from
      high quality males. To explore this hypothesis, we used the natural variation of
      the reproductive value that males and females undergo through age. The age
      related variation of phenotypic performance might then induce variations in
      mating strategies in males and females. Using the common lizard (Lacerta
      vivipara) as our model system, we showed that reproductive immaturity and
      senescence created variability in both male and female reproductive success
      (including survival of offspring). Consistent with theory, males at their best
      performing phenotype adopted a polygynous strategy. These males were of an
      intermediate age and they produced offspring of higher viability than younger and
      older males. In contrast, females at their best performing phenotype, also of an
      intermediate age, were less polyandrous than other less-performing females.
      Middle-aged females tended to mate with males of an intermediate age and produced
      litters with higher viability independently from their reproductive strategy.
      Males of an intermediate age enhanced their fitness by additional matings with
      young or old females. Young and old females increased their fitness by being more
      polyandrous. Polyandry therefore appears as means to seek for good males. A
      positive correlation between males and their partners' fitness disagree with the
      idea that polyandry is the result of a sexual conflict in this species.

PMID- 16101781
TI  - Multilocus estimation of pairwise relatedness with dominant markers.
AB  - Estimators for pairwise relatedness designed for dominant markers are derived,
      based on a genetic model that accounts for the full structure of pairwise
      relatedness between two individuals at a diploid locus with dominance. They
      jointly estimate 'relatedness' and 'fraternity', in which case the estimators are
      inherently multilocus, as at least two loci of differing gene frequency are
      required. Extensions to cases of zero fraternity and isolation by distance
      (inbreeding) are also examined. Properties of estimators are examined by
      simulation and compared to the estimator of Hardy. The most statistical power for
      pairwise relatedness occurs when roughly half of individuals are the recessive
      phenotype. Estimation procedures are implemented in the computer program mark.

PMID- 16101782
TI  - The inadvertent introduction into Australia of Trypanosoma nabiasi, the
      trypanosome of the European rabbit (Oryctolagus cuniculus), and its potential for
      biocontrol.
AB  - Wild rabbits (Oryctolagus cuniculus) in Australia are the descendents of 24
      animals from England released in 1859. We surveyed rabbits and rabbit fleas
      (Spilopsyllus cuniculi) in Australia for the presence of trypanosomes using
      parasitological and PCR-based methods. Trypanosomes were detected in blood from
      the European rabbits by microscopy, and PCR using trypanosome-specific small
      subunit ribosomal RNA (SSU rRNA) gene primers and those in rabbit fleas by PCR.
      This is the first record of trypanosomes from rabbits in Australia. We identified
      these Australian rabbit trypanosomes as Trypanosoma nabiasi, the trypanosome of
      the European rabbit, by comparison of morphology and SSU rRNA gene sequences of
      Australian and European rabbit trypanosomes. Phylogenetic analysis places T.
      nabiasi in a clade with rodent trypanosomes in the subgenus Herpetosoma and their
      common link appears to be transmission by fleas. Despite the strict host
      specificity of trypanosomes in this clade, phylogenies presented here suggest
      that they have not strictly cospeciated with their vertebrate hosts. We suggest
      that T. nabiasi was inadvertently introduced into Australia in the 1960s in its
      flea vector Spilopsyllus cuniculi, which was deliberately introduced as a
      potential vector of the myxoma virus. In view of the environmental and economic
      damage caused by rabbits in Australia and other islands, the development of a
      virulent or genetically modified T. nabiasi should be considered to control
      rabbits.

PMID- 16101783
TI  - Growth, productivity, and competitiveness of introgressed weedy Brassica rapa
      hybrids selected for the presence of Bt cry1Ac and gfp transgenes.
AB  - Concerns exist that transgenic crop x weed hybrid populations will be more
      vigorous and competitive with crops compared with the parental weed species.
      Hydroponic, glasshouse, and field experiments were performed to evaluate the
      effects of introgression of Bacillus thuringiensis (Bt) cry1Ac and green
      fluorescent protein (GFP) transgenes on hybrid productivity and competitiveness
      in four experimental Brassica rapa x transgenic Brassica napus hybrid generations
      (F1, BC1F1, BC2F1 and BC2F2). The average vegetative growth and nitrogen (N) use
      efficiency of transgenic hybrid generations grown under high N hydroponic
      conditions were lower than that of the weed parent (Brassica rapa, AA, 2n = 20),
      but similar to the transgenic crop parent, oilseed rape (Brassica napus, AACC, 2n
      = 38). No generational differences were detected under low N conditions. In two
      noncompetitive glasshouse experiments, both transgenic and nontransgenic BC2F2
      hybrids had on average less vegetative growth and seed production than B. rapa.
      In two high intraspecific competition field experiments with varied herbivore
      pressure, BC2F2 hybrids produced less vegetative dry weight than B. rapa. The
      competitive ability of transgenic and nontransgenic BC2F2 hybrids against a
      neighbouring crop species were quantified in competition experiments that assayed
      wheat (Triticum aestivum) yield reductions under agronomic field conditions. The
      hybrids were the least competitive with wheat compared with parental Brassica
      competitors, although differences between transgenic and nontransgenic hybrids
      varied with location. Hybridization, with or without transgene introgression,
      resulted in less productive and competitive populations.

PMID- 16101784
TI  - Genomic organization of molecular differentiation in Norway spruce (Picea abies).
AB  - Diversity and differentiation among three populations representing the
      geographical domains commonly recognized within the natural distribution area of
      Picea abies were analysed by using a set of 292 AFLP (amplified fragment length
      polymorphism), SSR (single sequence repeat) and ESTP (expressed sequence tags
      polymorphism) markers. As usually observed in forest trees, results showed high
      within-population diversity (H(S) reaching 0.79) and low among-population
      differentiation (G(ST) approximately 2%). The genomic organization of
      differentiation was then investigated on the basis of a subsample of 150 AFLP,
      SSR and ESTP mapped markers. The number of the loci differentiating the Baltico
      Nordic from the central European populations (25 loci) and, within the central
      European populations, the Alpine from the Hercyno-Carpathian populations (12
      loci), were different. These 37 differentiated loci, with individual G(ST) values
      ranging from 0.008 to 0.20, were evenly distributed on all linkage groups and
      mostly followed the neutral expectations, suggesting genome-wide effects on
      differentiation. Nine of them however behave as 'outlier' loci indicating
      possible locus-specific selective effects. Contribution of ongoing evolutionary
      forces and historical effects to the geographical differentiation of the species
      are discussed.

PMID- 16101785
TI  - Gene expression patterns accompanying a dietary shift in Drosophila melanogaster.
AB  - The ability of many organisms to switch to new hosts can be critical to their
      survival in the wild. However, the genetic mechanisms underlying such shifts are
      poorly understood. In this study, we used complementary DNA (cDNA) microarrays to
      ask if changes in gene expression are observed in response to a dietary shift in
      Drosophila melanogaster, a dietary generalist. We found significant and
      repeatable differential expression in a number of genes related to metabolic
      function and stress, suggesting that a functional genomics approach will be
      useful in seeking loci involved in the ability of flies to utilize different
      resources.

PMID- 16101786
TI  - Genetic resistance to bovine tuberculosis in the Iberian wild boar.
AB  - Bovine tuberculosis (bTB) is an important re-emerging zoonotic disease, causing
      major economic losses and constraining international trade of animals and their
      products. Despite eradication programmes, some countries continue to encounter
      outbreaks, mainly due to wildlife acting as primary hosts or reservoirs. While
      the genetic component of tuberculosis in humans and cattle is well documented,
      the role of genetic factors as modulators of bTB resistance remains unclear for
      natural populations. To address this issue, we investigated the relative
      contribution of host genetic variability to susceptibility to bTB infection and
      disease progression in wild boars from southern Spain. We found that genetic
      heterozygosity is an important predictor of bTB, not only modulating resistance
      to infection but also influencing containment of disease progression in infected
      individuals. Our results provide further evidence that host genetic variability
      plays a central role in natural populations. Testing each marker separately
      reveals evidence of both general and single-locus associative effects on bTB and
      several loci reveal high homology to regions of the genome with known immune
      function. Our results may prove to be crucial for understanding outbreaks of bTB
      in wildlife that could potentially affect domestic livestock and humans.

PMID- 16101787
TI  - Marine landscapes and population genetic structure of herring (Clupea harengus
      L.) in the Baltic Sea.
AB  - Numerically small but statistically significant genetic differentiation has been
      found in many marine fish species despite very large census population sizes and
      absence of obvious barriers to migrating individuals. Analyses of morphological
      traits have previously identified local spawning groups of herring (Clupea
      harengus L.) in the environmentally heterogeneous Baltic Sea, whereas allozyme
      markers have not revealed differentiation. We analysed variation at nine
      microsatellite loci in 24 samples of spring-spawning herring collected at 11
      spawning locations throughout the Baltic Sea. Significant temporal
      differentiation was observed at two locations, which we ascribe to sympatrically
      spawning but genetically divergent 'spawning waves'. Significant differentiation
      was also present on a geographical scale, though pairwise F(ST) values were
      generally low, not exceeding 0.027. Partial Mantel tests showed no isolation by
      geographical distance, but significant associations were observed between genetic
      differentiation and environmental parameters (salinity and surface temperature)
      (0.001 < P < or = 0.099), though these outcomes were driven mainly by populations
      in the southwestern Baltic Sea, which also exhibits the steepest environmental
      gradients. Application of a novel method for detecting barriers to gene flow by
      combining geographical coordinates and genetic differentiation allowed us to
      identify two zones of lowered gene flow. These zones were concordant with the
      separation of the Baltic Sea into major basins, with environmental gradients and
      with differences in migration behaviour. We suggest that similar use of landscape
      genetics approaches may increase the understanding of the biological significance
      of genetic differentiation in other marine fishes.

PMID- 16101788
TI  - Sequence polymorphism of candidate behavioural genes in Drosophila melanogaster
      flies from 'Evolution canyon'.
AB  - This study focuses on the molecular features of three candidate behavioural genes
      in Drosophila melanogaster from the opposite slopes of Nahal Oren Canyon, Mount
      Carmel, Israel. These slopes display dramatic physical and biotic contrasts.
      Spatial variation of microclimatic conditions leads to adaptive differentiation
      and partial sexual isolation of populations, as suggested by our previous
      studies. The chosen candidate genes presumably contributing to genetic variation
      in sexual behaviour of Drosophila in the Canyon were desaturase, period, and no
      on-transient A. These genes are known to include polymorphic repeated sequences,
      insertions/deletions, or nucleotide substitutions. The idea was that their
      polymorphism might be one of the determinants of behavioural peculiarities of
      flies derived from the opposite slopes. Indeed, interslope differences in the
      sequence encoding the (Thr-Gly)n repeat (exon 5) of the period gene were
      established, suggesting evolutionary functional importance. In particular, we
      unraveled variation in the length and composition of this region in different NFS
      (north-facing slope) and SFS (south-facing slope) lines. The 'European' allele (n
      = 20) was a 2.6-fold more abundant on the NFS compared to the SFS. This
      predominance probably gives some advantages for flies inhabiting wet and less
      warm conditions of the NFS. We suggest that repeat length/composition may
      influence the functional features of flies, i.e. habitat choice, nonrandom
      mating, and temperature adaptation. A series of female single-mate-choice tests
      show that females derived from NFS distinguish between males with specific per
      alleles (n = 17 vs. n = 20), as well as between males originated from the
      opposing slopes. Females from SFS were less discriminating and did not manifest
      significant deviation from random mating.

PMID- 16101789
TI  - Barcoding generalist predators by polymerase chain reaction: carabids and
      spiders.
AB  - Identification of arthropod predators is challenging when closely related species
      are found at a given locality. Identification of the immature stages is
      especially problematic, because distinguishing morphological features are
      difficult to use or have not been described. We used polymerase chain reaction
      (PCR) to distinguish closely related carabids and spiders, and to match eggs and
      larvae (or nymphs) with identified adult parents. Within the Carabidae, we
      amplified species-specific mitochondrial cytochrome oxidase I (COI) fragments for
      three species each in the genera Poecilus and Harpalus, and two each in Chlaenius
      and Bembidion. Within the Araneae, we amplified species-specific COI fragments
      for two Hibana species (Anyphaenidae), Pardosa milvina and Rabidosa rabida
      (Lycosidae), Frontinella communis and Grammonota texana (Linyphiidae), and
      Cheiracanthium inclusum (Miturgidae). We are able to correctly identify all
      immature stages tested--eggs, larvae (or nymphs) and pupae--by comparison of the
      amplified fragments with those of the adults. Using COI markers as species
      identifiers is a tenet of the Barcode of Life initiative, an international
      consortium to provide a molecular identifier for every animal species.

PMID- 16101790
TI  - Detection, identification and geographical distribution of European corn borer
      larval parasitoids using molecular markers.
AB  - Biological control requires specific tools for the accurate detection and
      identification of natural enemies, and to detect unusual variations in their
      density, which may follow changes in agricultural practices. Here we have
      developed specific molecular markers to detect Lydella thompsoni (Herting) and
      Pseudoperichaeta nigrolineata (Walker) (Diptera: Tachinidae) within the European
      corn borer, Ostrinia nubilalis (Hubner) (Lepidoptera: Crambidae). Primers
      amplifying fragments of the mitochondrial COI gene were designed following
      alignment of comparable sequences for a range of parasitoid and host species.
      Each of the primer pairs proved to be species specific to a tachinid species,
      amplifying DNA fragments of 191 and 91 bp in length for L. thompsoni and P.
      nigrolineata, respectively. This DNA-based technique allowed molecular evaluation
      of parasitism in O. nubilalis natural populations. In order to study the
      geographical distribution of both species in France, O. nubilalis diapausing
      larvae in maize stalks were collected from 12 locations over the whole country.
      The molecular evaluation of parasitism was compared with the traditional method
      of maintaining O. nubilalis populations in controlled conditions before breaking
      off the diapause. The percentage parasitism found in both species of tachinids
      was higher--approximately three times--using the molecular method, suggesting an
      underestimation by the traditional rearing protocol. Tachinid parasitism on O.
      nubilalis was not significantly different between geographical areas (south,
      central and north France) for both species. This study shows that molecular
      methods are very promising for the correct detection and identification of
      tachinid parasitoids in natural field populations.

PMID- 16101791
TI  - Interfamilial characterization of a region of the ZFX and ZFY genes facilitates
      sex determination in cetaceans and other mammals.
AB  - Sequence polymorphism of homologues ZFX and ZFY, in a 604-base pair exon region,
      was examined in 10 known males and 10 known females across seven cetacean
      families and used to design a simple, highly sensitive and widely applicable
      fluorescent 5' exonuclease assay for gender determination in cetaceans. Multiplex
      amplification, cloning, and sequencing of these previously uncharacterized
      regions revealed (i) eight fixed differences between ZFX and ZFY, (ii) 29
      variable sites between ZFX and ZFY and (iii) very low interspecific nucleotide
      diversity for both ZFX and ZFY across all families examined. We developed a 5'
      exonuclease assay that produces a small (105 bp) polymerase chain reaction (PCR)
      product from both the X and the Y chromosome orthologs, and used double-labelled
      fluorescent probes to distinguish between the two genes in a real-time PCR assay
      that is highly reproducible and sensitive. We demonstrated sex specificity for 33
      cetacean species in nine families. Given the availability of conserved primers
      and sequence information for many mammalian species, this approach to designing
      sexing assays for a wide range of species is both practical and efficient.

PMID- 16101793
TI  - Treatment of canine Old World visceral leishmaniasis: a systematic review.
AB  - Canine visceral leishmaniasis is a systemic disease caused by Leishmania
      infantum. The aim of this systematic review was to identify and evaluate the
      evidence of efficacy of interventions for treatment or prevention of canine
      visceral leishmaniasis, and to propose recommendations for or against their use.
      Forty-seven articles describing clinical trials published between 1980 and 2004
      fulfilled selection criteria. The evaluation of clinical trials provided good
      evidence for recommending the use of meglumine antimoniate at a minimum dosage of
      100 mg kg(-1) daily for at least 3-4 weeks, combined with allopurinol in order to
      obtain a good clinical efficacy and a reduced relapse rate. The evaluation of the
      articles also provided fair evidence for recommending the use of pentamidine (4
      mg kg(-1) twice weekly) and aminosidine (5 mg kg(-1) twice daily) for 3-4 weeks.
      There was insufficient evidence for recommending the use of allopurinol alone,
      amphotericin B, buparvaquone, ketoconazole, enrofloxacin, and the combinations of
      metronidazole with spiramicyn or metronidazole with enrofloxacin. Fair evidence
      against the use of aminosidine at high dosages (20-80 mg kg(-1) per day) was
      proposed due to its side effects. Evaluation of articles on repellent measures
      against sand fly vectors of leishmaniasis provided good evidence for recommending
      deltamethrin collars and fair evidence for recommending spot-on permethrin.

PMID- 16101794
TI  - PCR technique detection of Leishmania spp. but not Mycobacterium spp. in canine
      cutaneous 'sterile' pyogranuloma/granuloma syndrome.
AB  - Cutaneous 'sterile' pyogranuloma/granuloma syndrome (SPGS) is an uncommon canine
      skin disorder of unknown aetiopathogenesis. Histopathological findings and
      failure to demonstrate an aetiologic agent are suggestive of this syndrome.
      Nevertheless, it has been hypothesized that SPGS may be related to an immune
      response against persistent endogenous or exogenous antigens. The presence of
      Leishmania and Mycobacterium organisms was investigated by polymerase chain
      reaction (PCR) techniques in 46 canine skin samples histopathologically diagnosed
      as SPGS. Concomitantly, an immunohistochemical technique for Leishmania detection
      was applied on the same samples and the results were compared with those from
      PCR. The PCR technique yielded positive results for Leishmania spp. in 21 out of
      46 skin samples. The results of immunohistochemical techniques were identical to
      those obtained by PCR. The PCR technique gave negative results for Mycobacterium
      spp. in all the samples examined. These results suggest the importance of looking
      for Leishmania spp. in skin biopsies with histopathological findings consistent
      with the diagnosis of SPGS.

PMID- 16101795
TI  - Clinical, histopathological and immunological characteristics of exfoliative
      cutaneous lupus erythematosus in 25 German short-haired pointers.
AB  - Clinical, histopathological and immunological features of exfoliative cutaneous
      lupus erythematosus, an uncommon generalized exfoliative dermatitis occurring
      exclusively in German short-haired pointers, were characterized in 25 dogs. The
      disease affects young adult dogs and its familial incidence strongly suggests a
      hereditary origin. Lesions were characterized by scaling and alopecia affecting
      100 (25/25) and 76% (19/25) of dogs, respectively. Follicular casts were present
      in 28% (7/25) of dogs. The muzzle, pinnae and dorsum were typically affected.
      Generalized skin lesions were described in 52% (13/25) of dogs. Systemic signs of
      pain and lameness affected several dogs. Anaemia and thrombocytopenia were
      detected in several dogs with a more severe clinical phenotype. The most common
      histopathological features were hyperkeratosis and a lymphocytic interface
      dermatitis. Direct immunostaining revealed IgG deposition in the epidermal and
      follicular basement membrane of 100 (19/19) and 41% (7/17) of dogs, respectively.
      Circulating antifollicular and antisebaceous gland IgG antibodies were
      demonstrated by indirect immunostaining in 57% (4/7) of dogs. This disease
      usually responds poorly to immunosuppressive therapy and it has a guarded
      prognosis. Where outcome was recorded, 85% (10/12) of dogs were euthanased due to
      either a failure to respond to, or complications associated with,
      immunomodulatory therapy. Two affected dogs are in remission and maintained on
      immunomodulatory dosages of prednisolone. This study demonstrates the existence
      of a cellular and humoral immune response directed against the epidermal basement
      membrane of dogs with exfoliative cutaneous lupus erythematosus. Additional
      studies are required to further characterize the immunological pathogenesis of
      this disease.

PMID- 16101796
TI  - Prevalence of the group 1 Dermatophagoides allergens Der p 1 and Der f 1 in homes
      with no dogs, healthy dogs and Dermatophagoides-sensitized atopic dogs in
      Liverpool.
AB  - Dermatophagoides farinae is a frequent allergen in canine atopic dermatitis
      despite its reported scarcity in the UK, and the aim of this study was to
      determine whether dogs were uniquely exposed to this species. Der f 1 and Der p 1
      in dust collected from living room carpets, bedroom carpets and dog beds of 13
      houses with no dogs, 13 with healthy dogs, and 16 with Dermatophagoides
      sensitized atopic dogs were quantified by ELISA. Der p 1 levels (microg g(-1)
      house dust) were significantly higher than Der f 1 in living rooms (Der p 1
      median = 1.9, 95% CI = 2.05-6.32, n = 42; Der f 1 median = 0.07, 95% CI = 0.01
      0.06, n = 42), bedrooms (Der p 1 median = 4.35, SD = 5.52; Der f 1 median = 0.01,
      95% CI = 0.001-0.1, n = 42) and dog beds (Der p 1 median = 1.04, 95% CI = 1.4
      8.1, n = 29; Der f 1 median = 0.008, 95% CI = 0.01-0.04, n = 29) (P < 0.0001).
      Living rooms in houses without dogs had significantly greater Der p 1 levels
      (median = 7.0, 95% CI = 3.53-15.8, n = 13) than houses with healthy (median =
      1.19, 95% CI = 0.44-3.49, n = 13) or atopic dogs (median = 0.78, 95% CI = 0.63
      2.42, n = 16) (P = 0.0004). Environmental flea control in living rooms and
      washing dog beds was associated with significantly reduced Der p 1 levels. This
      confirms that D. pteronyssinus is common but D. farinae is rare in the sampling
      area. Apparent sensitization to D. farinae is probably due to cross-reaction. A
      combination of environmental measures could reduce allergen exposure.

PMID- 16101797
TI  - Humoral measurement of type-1 hypersensitivity reactions to a commercial
      Malassezia allergen.
AB  - Malassezia pachydermatis is considered to be a contributing factor to canine
      atopic dermatitis (AD). The purpose of this study was to investigate the humoral
      response to a commercially produced M. pachydermatis extract. Fifteen atopic dogs
      with Malassezia overgrowth on the skin (MD), 16 atopic dogs without MD, three
      atopic dogs with overgrowth of Malassezia in the ears only (MO), and 12 normal
      dogs were intradermally tested with M. pachydermatis extract at 50, 100, 250,
      500, 1000, 2000 and 4000 PNU mL(-1). All dogs were evaluated cytologically by
      cutaneous tape strip and bilateral ear exudate sampling to determine presence of
      MD or MO. Each had serum evaluated for anti-Malassezia IgE using three Malassezia
      extracts with an ELISA assay. The irritant threshold concentration at which
      healthy nonatopic dogs ceased to react was 1000 PNU mL(-1). There was a
      significant difference in intradermal test reactivity between the atopic groups.
      At this dilution, 93% (14/15) of the atopic MD group, 31% (5/16) of the atopic
      group without MD or MO, and 100% (3/3) of the atopic MO only group reacted. There
      were no significant differences in the serum IgE levels as measured by the Greer
      ELISA assay, between any groups using any of the three extracts. These results
      support that Greer's M. pachydermatis extract is useful for intradermal testing
      of dogs with an allergic phenotype, and that atopics with MD are more likely to
      have a type-1 Malassezia hypersensitivity than those without. The ELISA assay may
      require further development in order to be useful for the diagnosis of Malassezia
      hypersensitivity.

PMID- 16101798
TI  - Zinc-responsive dermatosis in goats suggestive of hereditary malabsorption: two
      field cases.
AB  - Two cases of zinc deficiency in dairy goats from different flocks and not
      associated with a zinc-deficient diet are described. Hard, dry, hyperkeratotic
      skin, hair loss and pruritus especially prominent on the back, legs, udder, face
      and ears were the most common clinical signs. Skin biopsy findings revealed a
      mixture of orthokeratotic and parakeratotic hyperkeratosis. On initial
      examination, serum zinc concentrations were low in both goats (461 microg L(-1)
      and 521 microg L(-1), respectively). Although mild skin lesions persisted during
      the early stages of zinc supplementation, skin lesions completely resolved after
      prolonged oral zinc supplementation. Withdrawal of zinc supplementation resulted
      in re-appearance of lesions in both animals. Case 2 gave birth to two kids, one
      of which showed mild skin lesions at 8 months of age together with a low serum
      zinc concentration (434 microg L(-1)), suggestive of hereditary zinc
      malabsorption. The other kid remained free of skin lesions and had a serum zinc
      concentration (530 microg L(-1)) within the normal range. On the basis of
      historical and clinical findings, the cases presented here more closely resemble
      Syndrome 1 hereditary zinc deficiency as seen in Nordic dog breeds rather than
      other zinc deficiency conditions seen in other species. It is suggested that zinc
      deficiency in these goats was due to hereditary malabsorption of dietary zinc.
      This is the first descriptive study of this condition in goats. Life-long zinc
      supplementation may be necessary in such patients.

PMID- 16101799
TI  - Bilateral ear canal neoplasia in three dogs.
AB  - Bilateral ear canal infections are common in dogs. Ear canal neoplasia is usually
      associated with unilateral problems, and is uncommon in dogs. To the best of the
      author's knowledge, bilateral aural neoplasia has not been reported in dogs, and
      only four case reports were found in the human literature. This report presents
      three dogs that had bilateral tumours in their ear canals. They were presented
      with bilateral otitis externa. All three dogs exhibited tissue proliferation of
      both ear canals that did not respond to glucocorticoids. Treatment consisted of
      total ear canal ablation, and tissues were submitted for histopathological
      evaluation. Case # 1 (a 10-year-old, male cocker spaniel) was diagnosed as
      ceruminious gland carcinoma. Cases # 2 and 3 were diagnosed as squamous cell
      carcinoma. Case # 1 was diagnosed 4 years earlier as having keratinization
      disorder, which was causing its chronic ear problems. Case # 2 (a 5-year-old,
      female French bulldog) was diagnosed 4 years earlier as having atopic dermatitis,
      which did not respond to hyposensitization, and only partially responded to
      glucocorticoids therapy. Case # 3 (a 9-year-old, male German shepherd) was
      diagnosed by the referring veterinarian as having unilateral ear canal
      proliferation 2 months prior to presentation. However, otoscopic examination
      showed bilateral proliferation that obstructed both canals. In summary, bilateral
      ear canal neoplasia should be considered in cases of nonresponsive, proliferative
      aural pathology.

PMID- 16101800
TI  - Thymoma-associated exfoliative dermatitis in a rabbit.
AB  - A 5-year-old rabbit with generalized scaling is presented. Multiple skin
      scrapings and acetate tape impressions were negative for mites and Malassezia.
      Culture for dermatophytes was also negative. Skin biopsies showed similarities
      with sebaceous adenitis described in rabbits (absence of sebaceous glands,
      perifollicular lymphocytic infiltrate at the level of the absent sebaceous
      glands, lymphocytic mural folliculitis, interface dermatitis). The owners refused
      any treatment and 2 months later the rabbit was euthanized due to anorexia. At
      necropsy a mass was found in the anterior mediastinum. Histopathology confirmed a
      diagnosis of thymoma. A possible paraneoplastic skin disease was suspected, based
      on similarities with thymoma-associated exfoliative dermatitis in cats.

PMID- 16101801
TI  - Use of doramectin for treatment of sarcoptic mange in five Angora rabbits.
AB  - The efficacy of administering doramectin after moxidectin treatment, which has
      previously proved only partially effective, was evaluated in five Angora rabbits
      naturally infested with Sarcoptes scabiei mange. Evaluations included physical
      examination for clinical signs of sarcoptic mange and collection of skin
      scrapings for determination of mites. The rabbits first received two subcutaneous
      injections, 10 days apart, of moxidectin 1% injectable solution at a dosage of
      0.2 mg kg(-1) of bodyweight. Although moxidectin treatment resulted in clinical
      improvement within 10 days post initial injection, on days 10 and 35 post initial
      treatment live mites were present in skin scrapings. Administration of doramectin
      1% injectable solution using the same route and dosage and at similar intervals
      to moxidectin led to complete disappearance of signs of scabies and
      parasitological cure in all rabbits.

PMID- 16101802
TI  - The need for a Blood Transfusion Service.

PMID- 16101803
TI  - Pall eBDS: an enhanced bacterial detection system for screening platelet
      concentrates.
AB  - Bacterial contamination of blood components remains a significant problem in
      transfusion medicine. The Pall enhanced bacterial detection system (Pall eBDS)
      detects the presence of bacteria in leucodepleted platelet concentrates by
      measuring the reduction of oxygen in the sample, due to aerobic bacterial growth.
      Pooled platelet concentrates were spiked at 10 cfu mL(-1) with 10 organisms (one
      species per bag). Pall eBDS pouches were inoculated with the spiked platelet
      concentrates. After 24 and 30 h of incubation, the oxygen level was measured. A
      further set of pouches were taken from the inoculated platelet concentrates at 24
      h. Incubation and reading intervals were as for the initial set of pouches. A
      sensitivity study was also performed comparing the Pall eBDS with the BacT/ALERT
      system. Spiking at 10 cfu mL(-1) and immediately sampling into Pall eBDS pouches
      resulted in 97.6 and 100% detection after an incubation period of 24 and 30 h,
      respectively. After 24 h of incubation of the spiked platelet concentrates and
      then sampling into Pall eBDS pouches, 99.1% detection was obtained after
      incubation for both 24 and 30 h. The sensitivity of the Pall eBDS and BacT/ALERT
      is similar and in the order of 1 cfu mL(-1). Implementation of either BacT/ALERT
      or Pall eBDS for routine screening of platelet concentrates has the potential to
      further increase the safety of the blood supply.

PMID- 16101804
TI  - Amotosalen photochemical inactivation of severe acute respiratory syndrome
      coronavirus in human platelet concentrates.
AB  - A novel human coronavirus causing severe acute respiratory syndrome (SARS)
      emerged in epidemic form in early 2003 in China and spread worldwide in a few
      months. Every newly emerging human pathogen is of concern for the safety of the
      blood supply during and after an epidemic crisis. For this purpose, we have
      evaluated the inactivation of SARS-coronavirus (CoV) in platelet concentrates
      using an approved pathogen inactivation device, the INTERCEPT Blood System.
      Apheresis platelet concentrates (APCs) were inoculated with approximately 10(6)
      pfu mL(-1) of either Urbani or HSR1 isolates of SARS-CoV. The inoculated units
      were mixed with 150 microm amotosalen and illuminated with 3 J cm(-2) UV-A light.
      The viral titres were determined by plaque formation in Vero E6 cells. Mixing
      SARS-CoV with APC in the absence of any treatment decreased viral infectivity by
      approximately 0.5-1 log10. Following photochemical treatment, SARS-CoV was
      consistently inactivated to the limit of detection in seven independent APC
      units. No infectious virus was detected after treatment when up to one-third of
      the APC unit was assayed, demonstrating a mean log10-reduction of >6.2. Potent
      inactivation of SARS-CoV therefore extends the capability of the INTERCEPT Blood
      System in inactivating a broad spectrum of human pathogens including recently
      emerging respiratory viruses.

PMID- 16101805
TI  - Knowledge, attitude and practice survey regarding blood donation in a
      Northwestern Chinese city.
AB  - Recruitment of low-risk blood donors in developing countries is challenging. We
      studied the attitudes towards blood donation in several populations in a city in
      Western China. A survey of knowledge, attitude and practice was performed
      including 1280 individuals from eight distinct populations in Urumqi, Xinjiang
      Uyghur Autonomous Region, China. Included were Han Chinese and Uyghur populations
      of blood donors, non-donors, injection drug users, students and factory workers.
      Knowledge about blood donation varied between the groups. Factors motivating
      blood donation included social pressure, desire to know screening results and
      altruism. Inhibiting factors included fear of contracting an infection and other
      adverse health effects, including loss of vitality. Misconceptions about the
      effects of blood donation are widespread, even among educated persons in Urumqi.
      Fear of acquiring a serious infection may have been increased by the reports of
      HIV acquisition during plasma donations in China.

PMID- 16101806
TI  - A study of the prevalence of iron deficiency and its related factors in blood
      donors of Yazd, Iran, 2003.
AB  - Iron deficiency anaemia is an important limiting factor for the number of
      donations in regular donors. Limited data is available on the iron status in
      Iranian donors. This study was conducted to evaluate the prevalence of iron
      deficiency and its related factors in blood donors at Yazd blood transfusion
      centre, Iran. In this descriptive study, 337 persons accepted for donation in
      2003 were selected randomly. Haemoglobin, serum iron, total iron-binding capacity
      and ferritin concentrations were measured. Results showed that the prevalence of
      reduction in iron stores increased with an increase in the number of donations (P
      = 0.0001), such that reduction in iron stores was seen in all regular female
      donors (100%) and 48% of regular male blood donors. The prevalence of iron
      deficiency in female and male regular donors was 78 and 28%, whereas 55.6 and 16%
      of these donors had iron deficiency anaemia. Just one blood donation resulted in
      a significant increase in the prevalence of iron deficiency in women (P < 0.05),
      but in men, a significant increase was seen only in regular donors (P < 0.05). It
      is therefore recommended that blood donors should be educated about iron
      deficiency, and research studies should be performed to determine the best method
      of iron supplementation with minimal complications for all regular blood donors
      and women of childbearing age on their first donation.

PMID- 16101807
TI  - Costs associated with blood transfusions in Sweden--the societal cost of
      autologous, allogeneic and perioperative RBC transfusion.
AB  - Anaemia is characterised by an insufficient number of red blood cells (RBCs) and
      might occur for different reasons, e.g. surgical procedures are often with
      associated blood loss. Patients who suffer from anaemia have the option of
      treatment with blood transfusion or medical treatment. In this study, the
      societal cost, for the case of Sweden, of RBC transfusion using three different
      techniques, i.e. allogeneic, autologous and intraoperative transfusion, was
      estimated. The analysis was based on information from interviews with hospital
      staff at large Swedish hospitals and from published data. The average cost for a
      2 units transfusion was found to be Swedish kronor (SEK) 6330 (702 Euro) for
      filtered allogeneic RBCs and SEK 5394 (598 Euro) for autologous RBCs for surgery
      patients. Transfusion reactions accounted for almost 35 per cent of the costs of
      allogeneic RBC transfusions. The administration cost was found to be much higher
      for autologous transfusions compared with allogeneic transfusions. The cost of
      intraoperative erythrocyte salvage was calculated to be SEK 2567 (285 Euro) per
      transfusion (>4 units).

PMID- 16101808
TI  - A retrospective study evaluating single-unit red blood cell transfusions in
      reducing allogeneic blood exposure.
AB  - Although guidelines recommend the use of single-unit red blood cell (RBC)
      transfusions to minimize allogeneic blood exposure, clinical practice remains
      dominated by two-unit transfusions. This study assesses the potential impact of a
      single-unit transfusion policy on reducing RBC utilization. We performed a
      retrospective analysis of adult patients admitted to a tertiary care hospital who
      received one or two RBC units. In subjects transfused two units, the effect of
      one unit was estimated by dividing the change in haemoglobin by 2. The proportion
      of patients reaching a haemoglobin threshold of 70, 75, 80, 85 and 90 g L(-1)
      with a single RBC unit was estimated. Of 302 included patients, only 65 received
      a one-unit transfusion. Based on thresholds of > or = 90, > or = 80 and > or = 70
      g L(-1), a single-unit transfusion would be sufficient in 42.0% (RRR = 0.54),
      79.6% (RRR = 0.23) and 98.0% (RRR = 0.02) of cases, respectively. This
      corresponds to 0.21, 0.57 and 0.82 mean RBC units saved per patient. In the
      orthopaedic subpopulation, the mean RBC units saved are 0.53, 0.88 and 1.00 for
      the same haemoglobin targets. Adopting a policy of transfusing RBC in single-unit
      aliquots could significantly improve RBC utilization and decrease patient
      exposure to allogeneic blood.

PMID- 16101809
TI  - Whole blood versus red cells and plasma for exchange transfusion in ABO
      haemolytic disease.
AB  - Records of 381 neonates who underwent exchange transfusion (ET) due to ABO
      haemolytic disease at the Division of Neonatology of Hacettepe University,
      Ankara, Turkey, between January 1977 and December 2003 were reviewed. Records
      were kept for the type of blood used in ET, the number of ETs for each infant,
      adverse event attributable to ET and bilirubin levels before, and 4 and 8 h after
      each ET. Of 381 infants, 300 were transfused with whole blood, whereas 81 infants
      were transfused with O red cells suspended in A or B plasma. The re-exchange rate
      was higher in the whole blood group, compared with the erythrocyte and plasma
      group. Use of erythrocyte and plasma provided 30% reduction in the number of ETs
      per patient. Eight hours after the first ET, mean bilirubin levels were 84% of
      the pre-exchange values in the whole blood group and 73% of the pre-exchange
      values in the erythrocyte and plasma group (P = 0.001). As the use of O group red
      cells re-suspended in AB plasma decreased the re-exchange risk compared with O
      group whole blood, we suggest the use of O red cells re-suspended in AB plasma
      for the ET in cases of ABO haemolytic disease.

PMID- 16101810
TI  - The effect of continuous-flow automated plateletpheresis on fibrinolytic activity
      of donor plasma.
AB  - Blood circulating in extracorporeal circuit of the apheresis sets has a contact
      with an artificial surface. The data on the influence of plateletpheresis on
      fibrinolytic activity are very limited and difficult to interpret. The aim of our
      study was to estimate the effect of plateletpheresis on the activation of
      fibrinolysis. Plateletpheresis was performed in 17 healthy blood donors using
      continuous-flow cell separator COM.TEC (Fresenius, Bad Homburg, Germany). Before
      and after plateletpheresis, blood samples were taken and markers of fibrinolysis
      (PAP, t-PA, PAI-1) as well as factor XII activity have been measured. We observed
      statistically significant decrease in t-PA and factor XII activities after
      plateletpheresis. There were no significant changes in concentrations of t-PA,
      PAI-1 and PAP as well as PAI-1 activity after plateletpheresis. Plateletpheresis
      performed by COM.TEC cell separator has very little, if any, effect on the
      activation of fibrinolysis. The mechanism of the inhibition of t-PA activity
      needs further investigations.

PMID- 16101811
TI  - Harvesting peripheral blood progenitor cells from healthy donors with a short
      course of recombinant human granulocyte-colony-stimulating factor.
AB  - A short-course administration of non-glycosylated granulocyte-colony-stimulating
      factor (G-CSF) was investigated in 68 healthy donors (HDs) in order to collect >
      or = 4 x 10(6) CD34+ cells per kilogram of recipient's body weight. G-CSF was
      given at 10 microg/kg per day administered in two divided doses for 3 days.
      Leukapheresis was scheduled on day 4, 12 h after the last dose of G-CSF. A median
      of 35.6 circulating CD34+ cells microL(-1) (range, 3.1-185) was found on the day
      of leukapheresis. This allowed a median collection of CD34+ cells of 4.2 x 10(6)
      per kilogram of recipient's weight (range, 1.0-17.4). One single procedure was
      sufficient to reach the target level of CD34+ cells in 36 (53%) of 68 donors;
      significant correlations were found between the number of CD34+ cells collected
      on day 4 and the patient's sex, body-weight and volume of blood processed. A
      retrospective analysis was made with a historical group of HDs collected on day
      5. The day 5 schedule allowed a more consistent achievement of the target cell
      dose with one leukapheresis (P = 0.005) and resulted in the initial collection of
      a significantly larger number of CD34+ cells (P = 0.006).

PMID- 16101812
TI  - The genetic and phenotypic basis of blood group A subtypes in Koreans.
AB  - A serological and genetic study of Korean blood donors with phenotypic group A
      subtypes was performed. There were 176 donors with phenotypic A subtypes
      identified. Exons 6 and 7 from 57 representative donors were sequenced. The
      A(var) allele (784 G > A) was cloned and sequenced, and a family study
      demonstrating its inheritance and unusual serological characteristics was
      performed. The A102 allele was the most frequently identified allele in
      phenotypically A2 (58%, 11/19) and A2B (68%, 17/25) donors. Anti-A1 was rarely
      present amongst A2 and A2B donors. The family study revealed that the A(var)
      allele was expressed as phenotype A(weak)B in A(var)/B heterozygote members, but
      as phenotype O in A(var)/O heterozygotes. The most frequent allele in Korean
      donors with the A2 phenotype differs from its Caucasian counterpart, as does the
      frequency of anti-A1. The A(var) allele demonstrates allelic enhancement in
      A(var)/B heterozygotes.

PMID- 16101814
TI  - Abstracts of the Joint Conference of the Canadian Society for Transfusion
      Medicine, Canadian Blood Services and Hema-Quebec, Banff, Alberta, Canada, 21-24
      April 2005.

PMID- 16101813
TI  - Leucoreduction and variant Creutzfeldt-Jakob disease.

PMID- 16101815
TI  - Evidence for involvement of p59fyn in fasting-induced thymic involution.
AB  - p59fyn, a member of the src-family protein tyrosine kinase, is expressed
      abundantly in thymus. We examined the possible involvement of p59fyn in thymic
      involution induced by a fasting stress in Fyn-/- mice. An acute 48 h fast
      resulted in severe atrophy of the thymus and a marked decrease of the total
      thymocyte number with depletion of the CD4+CD8+[double positive (DP)] population
      in Fyn+/+ (control) mice. A remarkable increase in terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labelling-positive signals was detected
      in the fasted group of control mice. However, these findings were not observed in
      Fyn-/- mice. Interestingly, MRL/MPJ-lpr/lpr, a Fas-deficient model animal, also
      showed no significant decrease of DP cell numbers in the fasted group. p59fyn is
      known to interact with Fas signalling, and these findings suggest that p59fyn is
      involved in fasting-induced thymic involution, raising the possibility that
      Fas/p59fyn-mediated signalling may, at least partially, be associated with the
      phenomenon.

PMID- 16101816
TI  - Enhanced maturation and functional capacity of dendritic cells induced by
      mannosylated L2 domain of ErbB2 receptor.
AB  - The nature of antigens and functional state of dendritic cells (DC) are important
      in antigen presentation. The ability of DC for the induction of T-cell responses
      is promoted by maturation. It has been confirmed that mannose receptors mediate
      highly efficient endocytosis and presentation of mannosylated proteins. In the
      present study, L2 domain of ErbB2 ectodomain was expressed in Escherichia coli,
      purified and mannosylated. The maturation and functional capacity of DC induced
      by mannosylated L2 (mL2) protein were investigated. The results showed that L2
      protein could induce DC maturation, which was accompanied by elevated expression
      of MHC and co-stimulatory molecules. The effect of mL2 protein on DC maturation
      was more remarkable than that of non-mL2 proteins. Uptake of mL2 antigens by DC
      was more efficient. Furthermore, the T cells can be stimulated to proliferate in
      vitro and secrete Th1 and Th2 cytokines. Higher levels of both IFN-gamma and IL
      10 were detected from the T cells stimulated by mL2-pulsed DC, suggesting a
      concurrent activation of CD4+ and CD8+ T cells. The results demonstrated that L2
      domain of ErbB2 receptor is an immunodominant molecule. The mL2 domain of ErbB2
      can induce an enhanced maturation and functional capacity of DC. It may become an
      effective strategy to induce anti-ErbB2 response.

PMID- 16101817
TI  - Reactivation of antigen-induced arthritis in mice by oral administration of
      lipopolysaccharide.
AB  - We examined whether oral administration of lipopolysaccharide (LPS) from
      Escherichia coli reactivated antigen-induced arthritis (AIA) in mice that is one
      of models of human rheumatoid arthritis. To induce AIA, mice were immunized by
      subcutaneous injection of ovalbumin (OVA) emulsified with complete Freund's
      adjuvant into the base of the tail (day 0) followed by intraarticular injection
      of OVA on day 21. To investigate the ability of LPS to reactivate AIA, varying
      doses of LPS were p.o. administered 48 h after the challenge injection. The
      results showed that administration of LPS was followed by reactivation of AIA in
      a dose-related fashion. The reactivation of AIA by LPS was associated with
      increases in interferon-gamma, interleukin-1beta and tumour necrosis factor
      alpha. Polymyxin B sulfate given immediately before administration of LPS
      suppressed the reactivation of AIA. These findings suggest that LPS from
      intestinal bacteria may play a role in the reactivation of joint inflammation in
      which immune responses to pathogenic antigens are involved.

PMID- 16101818
TI  - Requisite role for complement C5 and the C5a receptor in granulomatous response
      to mycobacterial glycolipid trehalose 6,6'-dimycolate.
AB  - The development of pulmonary granulomatous lesions during mycobacterial infection
      is a complex phenomenon, in part caused by responses elicited towards the surface
      glycolipid trehalose 6,6'-dimycolate (TDM; cord factor). The molecular mechanisms
      underlying granuloma formation following challenge with TDM are not yet
      completely understood. The present study defines pathologic differences in acute
      response to Mycobacterium tuberculosis TDM in C57BL/6 mice and mice lacking the
      C5a receptor (C5aR-/-). Mice were intravenously injected with TDM prepared in
      water-in-oil-in-water emulsion and examined for histologic response and changes
      in proinflammatory cytokines and chemokines in lung tissue. Control C5a receptor
      sufficient mice demonstrated a granulomatous response that peaked between days 4
      and 7. Increased production of macrophage inflammatory protein-1 alpha (MIP
      1alpha), interleukin-1beta (IL-1beta) and CXC chemokine KC (CXCL1) correlated
      with development of granulomas, along with modest change in tumor necrosis factor
      alpha (TNF-alpha). In contrast, the C5aR-/- mice revealed markedly exacerbated
      inflammatory response. The receptor-deficient mice also demonstrated a lack of
      coherent granulomatous response, with severe oedema present and instances of
      lymphocytic cuffing around pulmonary vessels. Lung weight index was increased in
      the C5aR-/- mice, correlating with increased MIP-1alpha, KC, IL-1beta and TNF
      alpha over that identified in the congenic C5aR-sufficient controls. Correlate
      experiments performed in C5-deficient (B10.D2-H2d H2-T18c Hco/oSnJ) mice revealed
      similar results, leading to the conclusion that C5 plays a significant role in
      mediation of chemotactic and activation events that are the basis for maturation
      of granulomatous responses to TDM.

PMID- 16101819
TI  - Clearance of Chlamydia pneumoniae infection in H-2 class I human leucocyte
      antigen-A2.1 monochain transgenic mice.
AB  - CD8+ T cells have been suggested to play an important role in protective immunity
      against pulmonary Chlamydia pneumoniae infection in mice. Moreover, several
      classical major histocompatibility complex class I - restricted cytotoxic CD8+ T
      lymphocytes (CTL) specific for C. pneumoniae- derived peptides have been
      identified. Here, we studied the outcome of C. pneumoniae infection in human
      leucocyte antigen (HLA)-A2.1 transgenic mice (HHD mice) that are only able to
      express a classical human class I molecule (HLA-A2.1). C. pneumoniae infection
      was self-restricted in HHD mice which were able to develop specific immune
      responses and a protective immunity against a subsequent rechallenge in a manner
      comparable to wildtype mice. Furthermore, accumulation of functional and C.
      pneumoniae-specific T cells to the site of infection was detected after
      challenge. Antigen processing and HLA-A2.1-dependent presentation was studied by
      immunizing the HHD mice with chlamydial outer protein N (CopN). Isolation of a
      peptide-specific CTL line from the CopN-immunized mice suggests that the HLA-A2.1
      molecule can support the development of CTL response against a chlamydial protein
      in mice. These findings suggest that the transgenic mouse model can be used for
      further characterization of the HLA-A2.1-restricted CD8+ T-cell response during
      C. pneumoniae infection and for identification of CD8 epitopes from chlamydial
      antigens.

PMID- 16101820
TI  - The immunostimulatory peptide WKYMVm-NH activates bone marrow mouse neutrophils
      via multiple signal transduction pathways.
AB  - G-protein-coupled receptors play a major role in the activation of the innate
      immune system, such as polymorphonuclear neutrophils. Members of the formyl
      peptide receptor family recognize chemotactic peptides as well the amyloid-beta
      peptide and fragments of the human immunodeficiency virus envelope and may thus
      be implicated in major pathologies. The peptide WKYMVm-NH2 probably activates the
      receptor FPRL1 and its mouse orthologues Fpr-rs1 and Fpr-rs2. We examined the
      stimulation of C57BL6 mouse neutrophils by WKYMVm-NH2 and the effects of several
      inhibitors for intracellular signalling pathways (wortmannin, LY 294002,
      staurosporin, H-89, U 73122, thapsigargin and SKF 96365). We show here that
      WKYMVm-NH2 is a powerful stimulator of primary and secondary granule exocytosis
      as well as superoxide production. The signalling pathway involves
      phosphoinositide 3-kinase, protein kinase C, phospholipase C and store-operated
      calcium influx. Studies with peptide antagonists suggest that WKYMVm-NH2
      preferentially activates exocytosis via FPRL1 and not FPR, the major receptor for
      N-formylated peptides such as fMLF. However, the signalling pathways activated by
      WKYMVm-NH2 in mouse neutrophils are similar to those activated by fMLF in human
      neutrophils. Thus, the effect and the signalling pathways of the two agonists and
      their receptors are at least partially overlapping.

PMID- 16101821
TI  - Cytokine responses to fungal pathogens in Kupffer Cells are Toll-like receptor 4
      independent and mediated by tyrosine kinases.
AB  - Disseminated fungal infections are increasing. However, the interactions between
      the body's largest population of tissue macrophages, the Kupffer cells and the
      fungal pathogens are scarcely understood. The aim of this study was to examine
      the involvement of Toll-like receptor 4 (TLR4) signalling in cytokine production,
      using primary cultures of rat and murine Kupffer cells exposed to Aspergillus
      fumigatus and Candida albicans hyphae and conidia. All fungal components induced
      the release of tumour necrosis factor-alpha (TNF-alpha), but with delayed
      kinetics compared with lipopolysaccharide (LPS). Candida albicans was the most
      potent inducer of TNF-alpha protein and mRNA and the only inducer of interleukin
      10 (IL-10) in rat Kupffer cells. All fungal components induced enhanced mRNA
      levels of macrophage inhibitory protein-2 (MIP-2) in the cells, similar to LPS.
      Inhibitors of Src tyrosine kinases added to cells prior to stimulation led to
      attenuation in the release of both TNF-alpha (60%, P < 0.05) and IL-10 (70%, P <
      0.05) induced by C. albicans conidia but did not influence the LPS-mediated
      cytokine release. Murine Kupffer cells (C57BL/10J) also released TNF-alpha as
      well as the chemokines keratinocyte-derived chemokine (KC) and MIP-2 in response
      to fungal component. Surprisingly, Kupffer cells from TLR4-deficient C57BL/ScCr
      mice exhibited significantly enhanced production of KC and MIP-2 upon stimulation
      by fungal components compared with control littermates (P < 0.05). Our study
      demonstrates that Aspergillus and Candida components induce cytokine production
      in rat Kupffer cells and that the response to C. albicans conidia involves Src
      tyrosine kinases. The experiments with TLR4-deficient Kupffer cells suggest that
      the cytokine response in these cells to fungal component is not mediated by TLR4.

PMID- 16101822
TI  - Aspirin downregulates homocysteine formation in stimulated human peripheral blood
      mononuclear cells.
AB  - Moderate hyperhomocysteinaemia is established as an independent risk factor for
      atherosclerosis, thrombosis, stroke and dementia. Hyperhomocysteinaemia is mostly
      caused by the deficiency of B-vitamins folate and vitamin B12, which are
      essential cofactors in the remethylation of homocysteine to methionine.
      Interestingly, moderate hyperhomocysteinaemia is also often observed in chronic
      diseases, in which also elevated immune activation markers such as neopterin or
      sTNFR-II are found. In order to simulate immune activation in vitro, human
      peripheral blood mononuclear cells (PBMC) were stimulated with mitogens.
      Stimulation significantly increased homocysteine production in comparison with
      unstimulated PBMC; in parallel also neopterin formation was induced. Homocysteine
      formation was due to cell proliferation, proliferating T lymphocytes, and also
      the myelomonocytic cell line U-937 produced homocysteine. Treatment with the anti
      inflammatory drug aspirin dose-dependently inhibited homocysteine production and
      also neopterin formation in human PBMC. Treatment with salicylic acid showed
      similar effects as aspirin; FACS analysis showed that both compounds inhibited
      cell proliferation by arresting cells in the G0/G1-phase. In U-937, both
      compounds also slightly induced apoptosis at 5 mm. Proliferation-induced
      homocysteine formation and in parallel also monocyte activation can be suppressed
      effectively by aspirin and salicylic acid in vitro, suggesting that also in vivo
      aspirin may downregulate not only inflammation but also formation of
      homocysteine.

PMID- 16101823
TI  - Allergen challenge alters intracellular cytokine expression.
AB  - The pathophysiology of asthma is complex and engages cascades of events in the
      cytokine network. We, therefore, investigated the impact of bronchial allergen
      challenge in humans on the cytokine profile of circulating lymphocytes.
      Peripheral blood samples from 10 patients with allergic asthma were collected
      before and 24 h after allergen provocation. Patients who mounted a late-phase
      reaction were designated dual responders opposite to single responders. Whole
      blood cells were stimulated by mitogen and intracellular interleukin (IL)-4 and
      interferon (IFN)-gamma were detected by flow cytometry. The allergen challenge
      induced a decrease in IL-4+CD4+ cells in the patients (P = 0.05), and a
      significant decrease (P < 0.05) in IFN-gamma+CD4+ cells was noted in single, but
      not dual, responders. In addition, there was a significant difference (P < 0.01)
      with respect to the changes in the IFN-gamma+CD4+ cells comparing dual and single
      responders. No corresponding changes were observed in CD8+ cells. The data
      suggest a possible on-going traffic of IFN-gamma and IL-4+CD4+ lymphocytes into
      the bronchial mucosa in relation to an allergen challenge and generate the
      hypothesis that a difference exists between single and dual responders in this
      respect. Because the CD4+IFN-gamma-producing cells have the capacity to
      downregulate the T-helper type 2 response, a reduced capacity in this aspect
      might contribute to the pathophysiology in dual responders.

PMID- 16101824
TI  - Intrahepatic CD4 T-Cell apoptosis is related to METAVIR score in patients with
      chronic hepatitis C virus.
AB  - Hepatitis C virus (HCV) infection leads to liver injury, which is thought to be
      immune-mediated. Apoptosis of hepatic T cells could influence histological
      damage. We quantified peripheral and intrahepatic T-cell apoptosis in 28 patients
      with chronic hepatitis C by using cytofluorometric techniques. METAVIR score and
      HCV plasma viral load were determined. Six liver biopsies, obtained from controls
      without chronic hepatitis during hepatobiliary surgery, served as controls. In
      patients, liver T-cell apoptosis was upregulated compared to peripheral T cells:
      35 versus 7% for CD4+ and 56 versus 13% for CD8+ T cells (P < 0.001). Liver T
      cell apoptosis levels from patients were increased compared to controls for both
      CD4+ (P = 0.041) and CD8+ T cells (P = 0.007). Nine patients exhibiting METAVIR
      scores A and F < or = 1 showed higher intrahepatic CD4+ T-cell apoptosis compared
      to the 19 patients with a higher METAVIR score (P = 0.001) and both histological
      activity and fibrosis were related to apoptosis level. There was also an inverse
      relationship between the level of intrahepatic CD8+ T-cell apoptosis and serum
      transaminase activity (P = 0.023). Our study shows immune compartmentalization,
      suggesting that the study of peripheral blood lymphocytes may not be fully
      relevant to the pathophysiology of HCV hepatitis, and that the severity of liver
      injury is inversely correlated with intrahepatic CD4+ T-cell apoptosis.

PMID- 16101825
TI  - Neurotrophic factors and clinical recovery in relapsing-remitting multiple
      sclerosis.
AB  - Pathogenic autoimmune cells are demonstrated to be able to produce neurotrophic
      factors during acute phase of multiple sclerosis (MS). In this study, we
      determined the production of various neurotrophins [brain-derived neurotrophic
      factor (BDNF), nerve growth factor (NGF), glial cell line-derived neurotrophic
      factor (GDNF), neurotrophin 3 (NT3) and neurotrophin 4 (NT4)] and some pro
      inflammatory cytokines [tumour necrosis factor-alpha (TNF-alpha) and interferon
      gamma (IFN-gamma)] by unstimulated peripheral blood mononuclear cells (PBMC) in
      21 relapsing-remitting MS patients during different phases of disease (stable,
      relapse and post-relapse). During acute phase of disease, we detected a
      considerable increase of BDNF, TNF-alpha and IFN-gamma production, while
      significantly higher levels of GDNF, NGF, NT3 and NT4 were found in post-relapse
      phase. When neurotrophin production was correlated with clinical outcome
      (complete or partial recovery from new symptoms), we found a significantly higher
      BDNF production in relapse phase followed by increased GDNF, NGF, NT3 and NT4
      levels during post-relapse phase in subjects with complete remission only. During
      relapse phase, we detected a significant increase of pro-inflammatory cytokines,
      that was more evident in patients with partial recovery. The neuroprotective
      potential of immune cells seems to be inversely correlated with disease duration
      and with the age of patients.

PMID- 16101827
TI  - Mechanisms of lymphocyte migration in autoimmune disease.
AB  - The recruitment of leukocytes to inflamed tissues plays an essential role in
      combating infection and promoting wound healing. However, in autoimmune diseases
      such as multiple sclerosis and diabetes, leukocytes enter tissues and contribute
      to inappropriate inflammatory responses, which cause tissue injury and
      dysfunction. In diseases of this type, lymphocytes play critical roles in
      initiating and maintaining these aberrant inflammatory responses. The aim of this
      review is to examine the mechanisms whereby T-lymphocytes enter tissues in
      autoimmune diseases and to compare these mechanisms between various organs and
      diseases. An overview of the mechanisms of leukocyte recruitment and the
      techniques used to study leukocyte trafficking is provided, focusing on the use
      of intravital microscopy as a tool to assess the functional microvasculature in
      vivo. We also discuss the series of tissue homing events which allow naive
      lymphocytes to first enter lymph nodes and undergo activation, then subsequently
      to home to the peripheral organ where their cognate antigen is present. Finally,
      we examine mechanisms of leukocyte recruitment in diseases such as multiple
      sclerosis, autoimmune diabetes, systemic lupus erythematosus, rheumatoid
      arthritis, inflammatory bowel disease and asthma.

PMID- 16101828
TI  - Frequency and distribution of alleles of canine MHC-II DLA-DQB1, DLA-DQA1 and DLA
      DRB1 in 25 representative American Kennel Club breeds.
AB  - The frequency and distribution of dog leucocyte antigens (DLA) class II -DQA1, 
      DQB1 and -DRB1 alleles were determined for 25 American Kennel Club (AKC)
      registered dog breeds, representing 360 dogs from each of the seven major
      performance categories. Six to twenty-eight (average n=11) dogs were studied per
      group, with the exception of the Akita dog (n=94). All dogs were unrelated with
      no common grandparents based on AKC pedigree records (F-value <0.125). DLA class
      II allelic diversity was broad across breeds; 31/61 published DLA-DRB1 alleles,
      11/18 published DLA-DQA1 alleles and 31/47 published DLA-DQB1 alleles were found
      among the 25 breeds. However, allelic diversity was severely limited within a
      breed. Seventeen of the DLA-DRB1 alleles were each found in only a single breed,
      and only seven alleles were shared by seven or more breeds. DLA-DRB1*00101 and
      DLA-DRB1*01501 were shared by 16 and 19 breeds, respectively. DLA-DQA1*00101 and
      DLA-DQA1*00601 alleles were shared by many breeds. The Rough Collie (DLA
      DQA1*00901), English Setter (DLA-DQA1*00101) and Scottish Terrier (DLA
      DQA1*00101) were monoallelic for DLA-DQA1. Eleven DLA-DQB1 alleles were each
      found only in a single breed and only seven alleles were shared by six or more
      breeds. DLA-DQB1*00201 and DLA-DQB1*02301 were shared by 17 and 18 breeds,
      respectively. Forty per cent of dogs typed were homozygous at DLA-DRB1, 52% at
      DLA-DQA1 and 44% at DLA-DQB1. Nine new DLA class II alleles were identified;
      three for DRB1 and six for DQB1. Comparison of our study of North American
      purebred dogs to previous European DLA surveys showed a similar use of common
      alleles consistent with known founder effects. However, more alleles were
      detected in European breeds, compared to their North American descendents,
      indicating that additional DLA class II diversity was lost when European breeds
      were established in North America.

PMID- 16101829
TI  - Development and characterization of human constitutive proteasome and
      immunoproteasome subunit-specific monoclonal antibodies.
AB  - Delta (Y), MB1 (X), and Z are the three catalytic beta-subunits located in the
      inner rings of the constitutive proteasome, an intracellular multicatalytic
      complex responsible for the generation of peptides presented by human leukocyte
      antigen (HLA) class I antigens to T cells. When cells are incubated with
      interferon-gamma, delta (Y), MB1 (X), and Z are replaced by LMP2, LMP7, and
      LMP10, respectively, leading to the expression of immunoproteasome which
      generates peptides with increased affinity for HLA class I antigens. The
      characterization of the expression of constitutive proteasome and
      immunoproteasome subunits in cells, normal tissues, and malignant lesions has
      been hampered by the lack or limited availability of constitutive proteasome and
      immunoproteasome subunit-specific monoclonal antibodies (mAbs), which are
      suitable for immunohistochemical staining. To overcome this limitation, we
      generated human delta (Y), MB1 (X), Z, LMP2, LMP7, and LMP10-specific mAb
      secreting hybridomas from BALB/c mice immunized with peptides and recombinant
      fusion proteins. The mAbs SY-5, SJJ-3, NB-1, SY-1, HB-2, and TO-7 were shown to
      be specific for delta (Y), MB1 (X), Z, LMP2, LMP7, and LMP10, respectively, as
      they react specifically with the corresponding molecules when tested with a human
      B lymphoid LG2 cell lysate in Western blotting and with the peptide derived from
      each molecule in enzyme-linked immunosorbent assay. The reactivity of the six
      mAbs with the corresponding intracellular antigens resulted in intracellular
      staining when the mAbs were tested with microwave-treated and saponin
      permeabilized cells in indirect immunofluorescence and with formalin-fixed,
      paraffin-embedded tissue sections in immunohistochemical reactions. These results
      suggest that the constitutive proteasome and immunoproteasome subunit-specific
      mAbs we have developed are useful probes to characterize the expression of
      proteasome subunits in normal tissues and in pathological lesions.

PMID- 16101830
TI  - Associations of major histocompatibility complex class I chain-related molecule
      polymorphisms with Behcet's disease in Caucasian patients.
AB  - HLA-B*51 is known to be associated with Behcet's disease (BD) in many ethnic
      groups. The pathogenic gene, however, may lie close to the HLA-B locus and
      therefore be in linkage disequilibrium with HLA-B*51. On the basis of the
      proximity of MIC genes to HLA-B, their expression pattern and their affinity for
      the activating NKG2D receptor on natural killer (NK) cells and gammadelta T
      cells, these molecules have been postulated as susceptibility factors in BD. DNA
      from 56 western European Caucasians with BD and 90 Caucasian controls were
      analysed by polymerase chain reaction using allele-specific primers for MICA and
      MICB alleles. An increased allele frequency of MICA*009 was found in the BD
      patient group (25.0%) when compared with the controls (7.2%). This was associated
      with a corresponding decrease in MICA*008 in the BD patients (36.6%) compared
      with the controls (46.7%), which was not significant. MICA*009 was strongly
      associated with the presence of HLA-B*51 in patients and controls. No significant
      difference in frequency of MICB alleles was found between patients and controls.
      Both HLA-B*51 and MICA*009 are strongly associated with BD in a pure Caucasian BD
      patient group, and the two alleles are in linkage disequilibrium. No MICB allele
      was found to associate significantly with the disease, an unexpected finding
      considering the close proximity of the MICA and MICB loci. Our results suggest
      that while MICB does not influence the development of BD, polymorphisms in MICA
      may be pathogenic, perhaps through the interaction with NK and gammadelta T
      cells.

PMID- 16101831
TI  - The haplotype block, NFKBIL1-ATP6V1G2-BAT1-MICB-MICA, within the class III-class
      I boundary region of the human major histocompatibility complex may control
      susceptibility to hepatitis C virus-associated dilated cardiomyopathy.
AB  - Cardiomyopathy is a heart muscle disease with impaired stretch response that can
      result in severe heart failure and sudden death. A small proportion of hepatitis
      C virus (HCV)-infected patients may be predisposed to develop dilated
      cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). The molecular
      mechanisms involved in the predisposition remain unknown due in part to the lack
      of information on their genetic background. Because the human leukocyte antigen
      (HLA) region has a pivotal role in controlling the susceptibility to HCV-induced
      liver disease, we hypothesized that particular HLA alleles and/or non-HLA gene
      alleles within the human major histocompatibility complex (MHC) genomic region
      might control the predisposition to HCV-associated DCM (HCV-DCM) and/or HCV
      associated HCM (HCV-HCM). Here, we present mapping results of the MHC-related
      susceptibility gene locus for HCV-associated cardiomyopathy by analyzing
      microsatellite and single nucleotide polymorphism markers. To delineate the
      susceptibility locus, we genotyped 44 polymorphic markers scattered across the
      entire MHC region in a total of 59 patients (21 HCV-DCM and 38 HCV-HCM) and 120
      controls. We mapped HCV-DCM susceptibility to a non-HLA gene locus spanning from
      NFKBIL1 to MICA gene loci within the MHC class III-class I boundary region. Our
      results showed that HCV-DCM was more strongly associated with alleles of the non
      HLA genes rather than the HLA genes themselves. In addition, no significant
      association was found between the MHC markers and HCV-HCM. This marked difference
      in the MHC-related disease susceptibility for HCV- associated cardiomyopathy
      strongly suggests that the development of HCV- DCM and HCV-HCM is under the
      control of different pathogenic mechanisms.

PMID- 16101832
TI  - Epitope analysis of immunoglobulins against gp20, a GPI-anchored protein of the
      human sperm surface homologous to leukocyte antigen CD52.
AB  - Gp20 is a sialylglycoprotein of the human sperm surface related to maturation and
      capacitation and is homologous to CD52, a glycosyl- phosphatidyl-inositol (GPI)
      anchored protein highly expressed in lymphocytes, monocytes, eosinophils, and
      epididymal cells, described by the monoclonal antibody family CAMPATH. The
      CAMPATH antigen is characterized by a very short peptide (12 amino acids) and an
      N-linked oligosaccharide chain bound to the asparagine located in the third
      position and a GPI anchor bound to the C-terminal serine. The CAMPATH epitope
      includes three amino acids at the C-terminus and part of the GPI anchor. It has
      been suggested that anti-gp20 interacts with the same peptide recognized by
      CAMPATH antibodies but with a different epitope, since it describes the
      corresponding antigen in a different way. For example, it localizes the
      corresponding antigen in the equatorial region of the sperm head when sperm are
      capacitated, whereas CAMPATH antibodies bind all over the sperm surface. Our
      results indicate that the anti-gp20 epitope does not include the peptide
      backbone, the GPI anchor, or the N-glycans but consists of O-linked
      oligosaccharide chains bound to a unique CD52 glycoform present both in sperm and
      leukocytes. This is suggested by results obtained using many different
      approaches, such as immunoblot analysis of gp20 after removal of N- and O-glycans
      and after jacalin (Artocarpus integrifolia agglutinin)-affinity chromatography.

PMID- 16101833
TI  - HLA class I and II polymorphisms in Azores show different settlements in Oriental
      and Central islands.
AB  - Human leucocyte antigen-A, -B, -Cw, -DRB1, -DQA1 and -DQB1 polymorphisms were
      examined in the Azorean population. The data were obtained at high-resolution
      level, using polymerase chain reaction (PCR) with sequence-specific primer, PCR
      sequence-specific oligonucleotides and sequence-based typing. The most frequent
      allele in each locus was: A*0201 (24.5%), B*510101 (9.8%), Cw*0401 (14.8%),
      DRB1*070101 (18.3%), DQA1*0201 (17.4%) and DQB1*0301 (19.4%). The predominant
      extended haplotype was A*0202-B*1503-Cw*0202-DRB1*090102-DQA1*0303- DQB1*0202
      (1.9%), which was found to be absent in the Portuguese mainland. The present
      study corroborates historical sources that say the Azores were populated not only
      by Portuguese but also by other Europeans, mostly Flemish people. Despite
      dendrogram analysis showing some remote Asian genetic affinities, the lack of
      specific alleles and haplotypes from those populations does not allow us to
      conclude for direct influence. Haplotype and allele frequencies in Azores show no
      homogeneous distribution between Oriental and Central islands of this
      archipelago. The Oriental islands harbour several haplotypes already found in
      mainland Portugal and identified as Mediterranean and European. The Central group
      of islands on the contrary clearly shows an influence of north Europeans (most
      probably derived from a well-documented Flemish settlement), with much less
      affinity to mainland Portugal.

PMID- 16101834
TI  - A mutated HLA-A*0101 allele in the colorectal cell line HCA-7.
AB  - The colorectal cell line HCA-7 expresses surface human leucocyte antigen-A*0201
      (HLA-A*0201), but lacks expression of HLA-A*0101 whilst the normal B-cell line
      (EVA-1224), derived from the same individual, expresses both surface HLA-A1 and
      HLA-A2. Amplification refractory mutation system-polymerase chain reaction
      analysis, using sequence-specific primers, suggested that HCA-7 has a mutation in
      a 7 base pair (bp) cytosine repeat sequence located at the beginning of Exon 4
      (bp 621-627). Cloning and sequencing revealed HCA-7 to have eight cytosine
      residues in this repeat sequence. In contrast, EVA-1224 contained only 7
      cytosines. Analysis of the mRNA for HLA-A*010 using reverse trancriptase
      polymerase chain reaction (RT-PCR), with an allele-specific 5' primer in exon 2
      (bp 253-271) and a series of 3' primers in exons 3, 4 and 7 and in the
      3'untranslated region, revealed that HCA-7 contained a shortened message
      terminating in the region of the exon 3/4 boundary. The insertion of an extra
      cytosine in this region, which is only two bases from the exon 3/4 splice site,
      is presumed to lead to a splicing defect between exons 3 and 4 resulting in the
      lack of expression of a functional HLA-A*0101 product. HCA-7 is mismatch repair
      (MMR) defective due to lack of expression of hMLH1 resulting from
      hypermethylation of the promoter region. The consequential increase in errors in
      single-nucleotide repeat stretches of DNA can account for the HLA-A*0101
      mutation. This has probably then been selected for in the tumour to enable escape
      from immune attack against an HLA-A*0101-restricted tumour-specific determinant
      that has also arisen as a result of the tumour being MMR defective.

PMID- 16101835
TI  - Identification of a new HLA-B variant, HLA-B*5615.
AB  - A new HLA-B allele, B*5615, has been identified in a Caucasian individual by
      sequence-based typing. This allele shows a sequence identical to that of HLA
      B*5601 except for two nucleotide substitutions that cause a change from TTA to
      TAC at codon 116 and an amino acidic change from Leucine to Tyrosine in the
      mature protein.

PMID- 16101836
TI  - Novel HLA-Cw*01 allele, Cw*010203, identified by sequence-based typing*.
AB  - In this report, we describe the identification of an human leucocyte antigen
      Cw*0102 (HLA-Cw*0102) nucleotide sequence variant, a new HLA-Cw*010203, in a case
      - control study by using sequence-based typing. Allele HLA-Cw*010203 showed one
      nucleotide difference with HLA-Cw*010201 by a silent substitution at codon 130
      (CTG-->CTA).

PMID- 16101837
TI  - Identification of four novel HLA-DOA alleles, DOA*010106, DOA*0102, DOA*0103, and
      DOA*0104N, by sequence-based typing*.
AB  - DOA sequences are currently known to have identical protein sequences. However,
      in this study, we report four novel allele types of human leucocyte antigen-DOA,
      including one synonymous and three non- synonymous amino acid changes from the
      Korean population. DOA*010106 has identical protein sequence with previously
      known DOA*010103 except one nucleotide difference at codon 45 (TCG-->TCA). In
      contrast, DOA*0102 and DOA*0103 have a sequence change at codon 99 (CTG-->GTG)
      and codon 105 (CGC-->TGC), causing non-synonymous amino acid changes, Leu99Val
      and Arg105Cys, respectively. In addition, DOA*0104N has a sequence deletion at
      codon 36 (CCC-->CC-), resulting in a frame shift leading to a stop codon at codon
      62.

PMID- 16101838
TI  - Identification of a novel human DRB1*13 allele by sequence-based DRB typing.
AB  - Herein, we report on a novel DRB1 allele (DRB1*1368) identified during sequence
      based HLA-DRB typing. This new DRB1 allele is identical to DRB1*1301 at exon 2
      except for a single-nucleotide substitution at codon 37, changing the amino acid
      Asn to Asp.

PMID- 16101839
TI  - A novel HLA allele, DRB1*1609, identified in the Chinese Han population*.
AB  - A novel human leucocyte antigen-DRB1*16 (HLA-DRB1*16) allele (DRB1*1609) has been
      identified by sequencing-based typing (SBT) in Chinese Han population. This new
      allele has identical nucleotide sequence to DRB1*160101 in exon 2, except for a
      single-nucleotide substitution from A to T at position 127. This change leads to
      an amino acid change from tyrosine to phenylalanin at residue 47 (Y47F). SBT was
      performed for cloned DRB1*16-specific polymerase chain reaction fragment. The
      serological phenotype of DRB1*1609 is equivalent to DR16 antigen.

PMID- 16101840
TI  - Nomenclature for factors of the HLA system, update April 2005.

PMID- 16101841
TI  - Nomenclature for factors of the HLA system, update May 2005.

PMID- 16101845
TI  - Being in an alien world: Danish parents' lived experiences when a newborn or
      small child is critically ill.
AB  - Parents of critically ill small children have received quite a lot of attention
      in nursing and allied health literature. However, no documented studies were
      found from Danish paediatric or neonatal contexts. The aim of the study therefore
      was to identify Danish parents' lived experiences during a newborn or small
      child's critical illness. The study was undertaken in a human caring perspective
      assuming that caring is primary and relational, and that persons are concerned
      when things matter to them. Thirteen parents were interviewed twice, and data
      were analysed following Van Manen's phenomenological methodology. The findings
      revealed that being a parent when a newborn or small child is critically ill
      resembled being in another world, alien from what they knew and had earlier
      experienced. The parents wanted to be close to the child, they were seeking for
      an understanding of what happened, and they felt inexperienced and insecure but
      at the same time they were attentive and vigilant. The sub-themes that were more
      prominent were 'a need to be there', 'What is going on?', 'being vigilant',
      'being a spectator to your own life', and 'oscillating between hope and
      hopelessness'. The study implies that the staff needs to help the parents
      perceive some kind of meaning of what is going on, to instill hope despite not
      knowing the outcome, and to accept and respect the parents' style of coping with
      stress and concern for their sick child.

PMID- 16101846
TI  - The diversity of family health: constituent systems and resources.
AB  - The purpose of this study was to explore changes in family health associated with
      child's chronic illness and hospitalization. The aim was to answer the following
      questions: (i) What kind of changes do families experience when a child in the
      family is afflicted by a chronic illness; and (ii) What kind of changes do
      families experience when their child is admitted to hospital? The data were
      collected in 2002 in interviews with 29 such families whose children were
      receiving treatment or who had previously received treatment on the paediatric
      wards of two hospitals in Finland. Data were collected until reaching theoretical
      saturation, in which no additional data are found. Data analysis was based on the
      grounded theory method, proceeding to the stage of axial coding. Family health
      was formed out of two different dimensions: the constituent systems and the
      resources of family health. The constituent systems describe the impact of the
      child's chronic illness and period of hospitalization at the level of both
      individual family members and the family as a whole. These systems were described
      by five categories: (i) ill child at the centre of family attention, (ii)
      siblings in a minor role, (iii) the child's illness governs parental well-being,
      (iv) the roller coaster of the couple relationship and (v) the whole family is
      ill. The resources promoting and maintaining family health were divided into six
      different categories: (i) creative and maintaining mental images, (ii) active
      involvement, (iii) internal coping means, (iv) reinforcement of coping means, (v)
      awareness and change of values and (vi) social network shares emotional burden
      and responsibility for care. The results of the study show that family health is
      highly vulnerable when a child has to be admitted to hospital because of a
      chronic condition. They should help nursing staff gain a clearer picture of the
      depth and diversity of family health and support the resources that promote
      family health. Future research should study the methods of family nursing used in
      the care of families with children with chronic conditions.

PMID- 16101847
TI  - Swedish child health care in a changing society.
AB  - BACKGROUND: Staff in Swedish child health care today feel a gap between policy
      and practice. By revealing the main lines in the development of child health
      care, we hoped to achieve a better understanding of the current trends and
      problems in today's Swedish child health care. METHODS: A selection of official
      documents about the development of child health care during the period 1930-2000
      was studied with the aid of discourse analysis. RESULTS: Four discourses were
      identified, which serve as a foundation for a periodization of the development of
      child health care. In the first period the main task of child health care,
      alongside checking on the development of the child, was to inform and educate the
      mothers. During the second period health supervision became the crucial task, to
      identify risks and discover abnormalities and disabilities. The third period
      focused on the discussion concerning the identification of health-related and
      social 'risk groups', and the work of child health care was increasingly geared
      to supervision of the parents' care of their children. Parents were to be given
      support so that they could cope with their difficulties by themselves. During the
      current period child health care is increasingly expected to direct its work
      towards the child's surroundings and the family as a whole and is now explicitly
      defined as an institution that should strengthen parents' self-esteem and
      competence. The level of responsibility for the child's health changed gradually
      during the different periods, from public responsibility to parental
      responsibility. The focus of efforts in child health care was changed from being
      general in the first and second periods to general and selective in period three,
      and then gradually becoming selective again in period four. While control of the
      child's physical health was central during the first two periods, psychosocial
      health came into focus in the last two, along with the importance of supporting
      the parents to enable them to handle their difficulties by themselves. CONCLUDING
      REMARKS: We noted that it was difficult to translate policy recommendations into
      practice. One reason was the shifting focus in child health care from the child's
      physical health to psychosocial problems which in itself meant a shift from
      descriptions of concrete and well-defined duties to more abstract and general
      descriptions of tasks which are by definition open to interpretation. Another
      reason for the noted difficulty was the transition from unambiguously described
      measures in terms of paternalistic regulation to more participatory and at the
      same time more expansive definitions of roles and responsibilities.

PMID- 16101848
TI  - Achieving harmony with oneself: life with a chronic illness.
AB  - This paper presents partial findings of a larger research project focusing on
      what it means to live with a chronic illness. Getting in harmony with oneself is
      a movement towards, and a form of, acceptance of the chronic suffering and
      disease. Some patients achieve this level of acceptance, while for others the
      obstacles of everyday life make this movement towards acceptance difficult.
      Achieving harmony with oneself is conditioned by the existence of hope and spirit
      of life/life courage and by the pressure of doubts on this hope. Doubts can shake
      this hope so that instead of moving towards acceptance, the patient drifts
      towards hopelessness and despair. The research design is qualitative and uses a
      phenomenological-hermeneutic approach. A total of 18 patients were interviewed,
      divided into three groups of six patients diagnosed with 'type I' diabetes,
      colitis ulcerosa and patients with coronary occlusion in the rehabilitation
      phase. The goal of the research was to derive patterns/themes common to the three
      diagnosed groups regarding the patients' view of health and disease in connection
      with chronic illness and to elucidate the significance of this view for how the
      patients coped with everyday life. The research method is inspired by Paul
      Ricoeur.

PMID- 16101849
TI  - Hospitalized patients experienced suffering in life with incurable cancer.
AB  - The concept 'suffering' has been central within nursing since Florence
      Nightingale. But few researchers have made empirical studies about the lived
      phenomenon. Several researchers within nursing agree that more research
      concerning individual groups of patients has to be initiated. Within research
      about patients with incurable cancer focus has been on death, the terminal period
      and patients experience of being dying. This qualitative study was initiated to
      describe the characteristics of a group of Danish hospitalized patients'
      experienced suffering in life with incurable cancer. Twenty-five semi-structured
      interviews were arranged with 12 patients ones a week within a period of 4 weeks.
      In week 2 and 4, the interviews were supplemented by questions developed on the
      basis of the potential signs of suffering which appeared during the participant
      observations that took place the day before each interview. C. S. Peirce's
      semiotic and phenomenological grounded theory of signs was used in order to
      identify the potential signs. A phenomenological methodology developed by A.
      Giorgi was used to develop and describe the general structure of the phenomenon.
      The phenomenon is described as: 'The experience of living in an increasingly
      unpredictable existents at the mercy of the body, the consciousness, the illness,
      the death, the treatment, the professionals, one's articulateness, the past, the
      present and the future, influenced by increasing powerlessness, loneliness and
      isolation, and the experience of existing in an persistent, and with time,
      unconquerable struggle to maintain and regain control'.

PMID- 16101850
TI  - Hindrance for patient participation in nursing care.
AB  - THE STUDY'S RATIONALE: Patients' influence in health care through participation,
      freedom of choice and information, is laid down in laws, national and local
      directives. In nursing care situations, the degree to which a patient
      participates depends on the nursing staff. Accordingly, hindrances for patient's
      participation during nursing care is an important question for the nursing
      profession. AIMS AND OBJECTIVES: The aim was to focus on Swedish Registered
      Nurses opinion of hindrances for patient participation in nursing care and to
      uncover the informants' perspectives in depth. METHODOLOGICAL DESIGN AND
      JUSTIFICATION: The study was limited to inpatient somatic care and has a
      qualitative approach. Data were collected through seven focus group interviews
      with 31 Registered Nurses from five hospitals. An analysis of the tape-recorded
      interview material was made, combining elements of content analysis with aspects
      of the Grounded Theory approach. ETHICAL ISSUES AND APPROVAL: The ethics of
      scientific work was followed. The participants gave informed consent. Verbal and
      written information was given as a guarantee that all information would be
      treated confidentially outside the focus group. Formal approval by ethical
      committee was not required according to national and local directives. RESULTS:
      Hindrance for patient participation in nursing care comprised three themes:
      Competence, Influence of significant others and Organization and work
      environment, and their seven underlying subthemes. CONCLUSIONS: The study
      clarified factors, which individually or combined may be hindrance for patient
      participation in nursing practice. Professional nurses must be able to find a
      balance for their patients' participation in nursing care activities through
      identification and coping with the hindrances. The three themes and seven
      subthemes here identified, can be used in patient care and its' evaluation, like
      also quality assurance of care and work organization and in nursing education.
      For further development replication studies are needed, like additional studies
      of patients and significant others.

PMID- 16101851
TI  - Living with chronic obstructive pulmonary disease: part I. Struggling with meal
      related situations: experiences among persons with COPD.
AB  - Reduced nutritional intake with low and decreased body weight can be a component
      of normal ageing. There is, however, also a greater risk for reduced nutritional
      intake within certain diagnoses, especially for chronic diseases. Malnutrition in
      chronic obstructive pulmonary disease (COPD) is caused by many factors. The
      relationship between COPD and low values of body mass index (BMI) is a known
      independent risk for mortality. For optimal support and care with special focus
      on nutritional status and interventions, caregivers need more knowledge about the
      meal-related situations (i.e. shopping for food, cooking and eating) of COPD
      patients. The aim of this study was to describe experiences of meal-related
      situations as viewed from the individual's perspective. The sample included eight
      women and five men with COPD recruited from five primary health clinics. The
      participants' average age was 68.9 years, with values of forced expiratory volume
      in 1 second (FEV(1) percentage) ranging from 18 to 69 and BMI values from 15 to
      40. A descriptive design with qualitative interviews and self-reported diaries
      were used and the data were later analysed using content analysis. Findings
      showed consistency between informants' COPD, nutritional status and descriptions
      of experiences in meal-related situations. Findings were disease-specific but
      were also found to be general- and age-related. Respondents described physical
      influences and positive and negative feelings in their meal-related situations.
      Feelings of dependence, level of activity, transport of food, having company or
      being alone, appetite, hunger and need of time were also mentioned. Most research
      reports reduced nutritional status from a medical perspective. To our knowledge,
      no study has reported the positive and negative feelings that arise when eating
      in persons with COPD. Malnutrition for persons with COPD is not only caused by
      eating difficulties: eating is an integral part of social situations as shown in
      this study.

PMID- 16101852
TI  - Effects of resident-oriented care on quality of care, wellbeing and satisfaction
      with care.
AB  - In a resident-oriented care model applied in nursing homes, the residents are
      assigned to primary nurses. These primary nurses are responsible for the total
      care of the residents assigned to them. The purpose of the present study, using a
      pretest, post-test and control group quasi-experimental design, was to evaluate
      the effects of the implementation of resident-oriented care on the following
      aspects of quality of care: coordination of care, instrumental aspects,
      expressive aspects, resident wellbeing and satisfaction with care, and family
      satisfaction with care. The study was carried out on somatic and psycho-geriatric
      wards in three nursing homes in the Netherlands. Data were collected by
      questionnaires, interviews and observations. The results of the study showed that
      the intervention was partly successful in the experimental group. Some aspects of
      the resident-oriented care model were not clearly evident. Moreover, the effects
      on quality-of-care aspects were limited. The results revealed that the
      'coordination of care' increased on half of the experimental wards. Furthermore,
      there was an indication that 'expressive aspects' changed in favour of the
      experimental wards. The implementation of resident-oriented care had no effect on
      resident wellbeing and satisfaction or on family satisfaction. Finally, the
      results are discussed in the light of some methodological limitations that often
      go together with intervention studies in the real world.

PMID- 16101853
TI  - Work-related psychosocial factors, worry about work conditions and health
      complaints among female and male ambulance personnel.
AB  - This study aimed at investigating the relationships between work-related
      psychosocial factors, worry about work conditions and health complaints (sleeping
      problems, headache and stomach symptoms) among female and male ambulance
      personnel. Out of 4000 ambulance personnel in Sweden, 1500 (300 female and 1200
      male personnel) were randomly selected. They answered a questionnaire including
      items on self-reported health complaints, individual characteristics, work
      related psychological demands, decision latitude, social support and worry about
      work conditions. Twenty-five per cent of the female and 20% of the male ambulance
      personnel reported two or more health complaints sometimes or often. According to
      the demand-control-support questionnaire, ambulance personnel reported a
      generally positive psychosocial work environment, although psychological demands
      were associated with sleeping problems, headache and stomach symptoms among both
      female and male ambulance personnel. Another factor that was significantly
      associated with health complaints among both genders was worry about work
      conditions. When worry about work conditions was added to the regression models,
      this variable took over the role from psychological demands as a predictor for
      health complaints among the female ambulance personnel. The prevalence of
      sleeping problems, headache and stomach symptoms were significantly associated
      with psychological demands among both female and male ambulance personnel.
      Notably, worry about work conditions seems to be an important risk factor for
      health complaints. This suggests that worry about work conditions should not be
      neglected when considering risk factors among ambulance personnel.

PMID- 16101854
TI  - Nutritional care of Danish medical inpatients--patients' perspectives.
AB  - Many patients do not eat and drink sufficiently during hospitalization. Surveys
      have shown that 30-50% of the elderly patients are undernourished when
      hospitalized, and for the majority of these patients their protein and energy
      requirements are not met during hospitalization. Diseased people often experience
      reduced appetite, aversion against certain types of food or nausea, and these
      symptoms are part of the explanation for insufficient consumption of food and
      drinks. In order to locate other possible explanations, this study investigate
      medical inpatients' experiences and satisfaction with the nutritional care. The
      patients included a total of 91 medical inpatients at two internal medical wards,
      Aarhus University Hospital, Denmark. Their average age was 72 +/- 11 years. They
      were individually interviewed about the food service and the nutritional care
      upon discharge. Patient satisfaction with the meals was overall high (90%). About
      80% found the meals to be very important, but they lacked information about the
      food service, and the patients-staff communication about the food service was
      poor. The results indicate that the nursing staff was exercising a 'knowledge
      monopoly' in relation to the food service. In conclusion, a majority of the
      patients did not perceive the nutritional care as part of the therapy and nursing
      care during their hospitalization.

PMID- 16101855
TI  - Do all health and social care professionals interact equally: a study of
      interactions in multidisciplinary teams in the United Kingdom.
AB  - Problems around deficits in interprofessional collaboration have been identified
      since the National Health Service (NHS) was introduced. It is within the context
      of the current policy focus on improving collaborative working that this study
      was undertaken. A direct observational study using the Bales' Interaction Process
      Analysis tool was carried out in two older persons teams to explore patterns of
      interaction in the multidisciplinary team meetings. Analysis revealed some key
      differences in the way in which different professions interacted. Occupational
      therapists, physiotherapists, social workers (SW) and nurses rarely asked for
      opinions and for orientation. The consultant (the individual in charge of the
      medical team) tended to have high rates for asking for orientation, giving
      opinions and giving orientation. Although some nurses did have high individual
      rates for the giving of orientation. The data from the research has highlighted
      that therapists, SWs and nurses are reluctance to voice their opinions in
      multidisciplinary teams and thus conformity may dominate its culture. It is
      suggested that therapists, SWs and nurses need to cite their opinions in teams
      more effectively if they are to be competent and committed patient-centred
      practitioners.

PMID- 16101856
TI  - Can a teaching and learning perspective deepen understanding of the concept of
      compliance? A theoretical discussion.
AB  - Patients' noncompliance is regarded as a major problem in health care and efforts
      have been made to understand the mechanisms behind compliance and noncompliance.
      The concept of compliance has been analysed and criticized because of the limited
      way it defines the roles of patients and health professionals and for being
      supportive of the authority of health professionals. Attempts have been made to
      change the paternalistic meaning of the concept of compliance and alternative
      terms have been introduced. However, there is a lack of studies about the
      teaching and learning component of compliance. The aim of this theoretical
      article was to examine the meaning of the concept of compliance as is it used in
      health care, and relate it to a patient-centred, teaching and learning
      perspective. It is argued that instead of focusing on noncompliant patient
      behaviour, it would be more powerful to focus on the way the patients experience
      and understand and on how to create conditions for developing understanding, as
      this in turn might influence the behaviour or way of acting. It is suggested that
      the teaching part of compliance could be carried out by 'to follow and let
      oneself be followed', which means a teaching and learning situation where the
      health professional follows the patient, guided by patient experiences, and need
      for understanding. At the same time it means that following the patient's
      experiences creates possibilities for the health professional to reason and act
      in a way that the patient can follow. The concept of 'play' is used when putting
      'to follow and let oneself be followed' into effect. To this end, the health
      professional needs to develop a considered pedagogical standpoint.

PMID- 16101857
TI  - The structure of Antonovsky's sense of coherence in patients with schizophrenia
      and its relationship to psychopathology.
AB  - The main aim of the study was to investigate whether the three hypothesized
      subscales of Antonovsky's sense of coherence (SOC) scale: comprehensibility,
      meaningfulness and manageability, can be found when measuring SOC in a sample of
      patients with schizophrenia living in the community. A further aim was to study
      the relationship between SOC and psychopathology. The concept of SOC has been
      proposed to explain successful coping with life stressors. A total of 120
      patients completed the SOC scale and the Brief Psychiatric Rating Scale (BPRS)
      was used to assess the psychopathology of the patients. The SOC scale was
      analysed by means of a factor analysis with a varimax rotation and the Spearman
      rank correlation test was used to test for associations between subscales,
      factors and psychiatric symptoms. A four-factor model presented the best solution
      and explained 48% of the total variation in SOC. The first factor, which included
      12-items of the SOC scale, turned out to be the most salient factor explaining
      29% of the total variation. All factors displayed some overlapping between items.
      Affective symptoms were negatively related to all the three subscales and the
      four factors of SOC, while positive symptoms were similarly related to two of the
      subscales and two of the factors while negative symptoms were not associated with
      any of the factors or subscales. The findings in this study corroborate those in
      studies with other patient groups and indicate that the theoretical framework of
      SOC should not be adopted uncritically. Furthermore, the use of the three
      subscales in the SOC scale in studies of patients with a severe mental illness is
      questioned and a further investigation of the relationship between SOC and
      psychopathology is proposed.

PMID- 16101858
TI  - Home care personnel's perspectives on successful discharge of elderly clients
      from hospital to home setting.
AB  - The successful discharge of elderly patients from hospital to home care is a
      process requiring co-operation between health and social care personnel in
      addition to their commitment and skills. During the discharge process it is
      important that health and social care professionals have a shared view of the
      health and mental status and needs of the patient so that appropriate plans for
      meeting these needs can be made. The aim of the study was to investigate home
      care personnel's (health and social care workers) views of which practices
      between the discharging hospital and home care are associated with the successful
      discharge of clients. Home care personnel in 22 Finnish municipalities (n = 1890,
      response rate 63%) received a questionnaire in spring 2001. When the respondents'
      background factors were standardized, the best predictors of successful discharge
      from the home care personnel's point of view were adequate information received
      about the treatment of the patient's illnesses and their functional ability and
      cognitive potentials, timely information about the discharge, and good co
      operation between the discharging hospital, and the home care, social care and
      health care workers working in home care. There were differences in the opinions
      of social care workers and health care workers working in home care. From the
      home care personnel's point of view the most important correlates of an elderly
      client's discharge from hospital to a home setting were factors associated with
      how they can best plan their work. Their perspective on the discharge process may
      diverge from clients and their informal care givers point of view. To ensure the
      successful discharge process we must take them all into account.

PMID- 16101859
TI  - The Impact of Patient Aggression on Carers Scale: instrument derivation and
      psychometric testing.
AB  - Patient aggression towards carers constitutes a problem for patients and carers
      alike. Patients' aggressive behaviour often leads to adverse consequences for
      carers, especially nurses. Various extensive instruments have been developed to
      measure such adverse effects on carers. The 'Impact of Patient Aggression on
      Carers Scale' (IMPACS) is a short instrument intended for use in monitoring
      negative consequences of such incidents. The items of the IMPACS were derived
      basically from a review of the literature on negative effects of patient
      aggression on nurses. The IMPACS was administered to a convenience sample of
      nurses working on 14 psychiatric acute admission wards in the German speaking
      part of Switzerland. Factor analysis led to the exclusion of three of the
      original items and to an interpretable three-factor solution with all factors
      demonstrating eigen values higher than 1. The factors demonstrate moderate to
      good internal consistency. Canonical correlation analysis using the dimensions of
      the Maslach Burnout Inventory (MBI) produced a correlation coefficient of 0.457,
      thus demonstrating external reliability. In spite of some caveats such as
      possible response bias and the necessity of the investigation of the test-retest
      stability of the scale this study suggests that the IMPACS is a good measure of
      adverse effects and thus merits further development.

PMID- 16101860
TI  - Vegetative pyoderma gangrenosum: a report of two new cases and a review of the
      literature.

PMID- 16101861
TI  - Skin disorders in Ashkenazi Jews: a review.

PMID- 16101862
TI  - A comparative study of superoxide dismutase, catalase, and glutathione peroxidase
      activities and nitrate levels in vitiligo patients.
AB  - BACKGROUND: Several groups have shown the involvement of oxidative stress in the
      pathophysiology of vitiligo. METHODS: In this study, we examined the erythrocyte
      and plasma activities of glutathione peroxidase and Cu/Zn superoxide dismutase,
      plasma nitrite/nitrate levels, and erythrocyte catalase activity in 23 vitiligo
      patients and 25 controls. RESULTS: The results show that erythrocyte superoxide
      dismutase activity and plasma nitrite/nitrate levels are high in vitiligo
      patients. CONCLUSIONS: Our study confirms that oxidative stress is involved in
      the pathophysiology of vitiligo, as indicated by the high levels of erythrocyte
      superoxide dismutase activity and plasma nitrite/nitrate.

PMID- 16101863
TI  - Skin disease patterns in Hormozgan, Iran.
AB  - BACKGROUND: Skin diseases are the most common cause of referrals to general
      practitioners and dermatologists, and are considered a health problem in
      developing countries. The aim of this study was to report the extent and patterns
      of skin diseases in southern Iran. METHODS: All new cases of skin diseases
      referred to Shahid Mohammadi Hospital, Bandar Abbas, Southern Iran over a 3-year
      period were retrospectively considered. The dermatologic diagnoses, sex and age
      were recorded for each patient and the diagnoses were classified according to the
      International Classification of Diseases (ICD-10). RESULTS: A total of 6841
      patients were referred to the dermatology clinic of the hospital (48.27% male and
      51.73% female). Infectious and parasitic diseases, including infections of the
      skin and subcutaneous tissues, were found to be the most common skin diseases
      (32.1%), followed by dermatitis and eczema (24.5%), disorders of the skin and
      subcutaneous tissue such as pigmentation disorders (9.7%), papulosquamous
      disorders (3.8%), urticaria and erythema (2.8%), burns, corrosion and unspecified
      injuries (3.3%), radiation-related disorders (2.3%), neoplasm (0.8%) and diseases
      of the oral cavity, salivary glands and jaw (0.3%). CONCLUSIONS: It appears that
      certain skin diseases such as dermatitis and eczema, superficial mycoses and
      scabies cause serious health problems in the region. Emphasis should be placed on
      this group of common skin diseases at all levels of personal health care, and
      suitable public health policies should be implemented in order to manage this
      problem rationally.

PMID- 16101864
TI  - Skin disease: clinical indicator of immune status in human immunodeficiency virus
      (HIV) infection.
AB  - BACKGROUND: Dermatological manifestations are seen at every stage of HIV/AIDS
      (human immunodeficiency virus), and are often the presenting features. These
      manifestations not only act as markers but also reflect the underlying immune
      status. OBJECTIVE: To establish skin diseases as clinical indicators of
      underlying immune status in HIV disease by estimating and correlating with the
      CD(4), CD(4) : CD(8) ratio. MATERIALS AND METHODS: The CD(4), CD(8), CD(4) :
      CD(8) ratios were estimated using the fluorescence activated cell sorter (FACS)
      count system in 20 asymptomatic HIV patients, 80 HIV patients with various skin
      manifestations and 72 healthy volunteers as the control group. RESULTS: In
      comparison with the CD(4) cell count of the control group (mean 885/mm(3),
      standard deviation 331), that of the HIV-positive individuals (mean 409.83/mm(3),
      standard deviation 263.07) was statistically correlated with low counts (z =
      10.099 and P < 0.05). Similarly there was statistical significance with the CD(4)
      : CD(8) ratio among these two groups. In comparison with the CD(4) cell count of
      the asymptomatic HIV-positive individuals (mean 620.65/mm(3) and standard
      deviation 262.065), the CD(4) cell count of the HIV-positive patients with
      various dermatological manifestations (mean 357.15/mm(3), standard deviation
      236.95) was statistically correlated with low counts (z = 4.0978 and P < 0.05).
      Similarly there was statistical significance with the CD(4) : CD(8) ratio among
      these two groups. CONCLUSIONS: There was an inverse relation between the CD(4)
      counts and the incidence and severity of skin diseases in the HIV/AIDS patients.
      Cutaneous manifestations of HIV can be considered as good clinical indicators to
      predict and access the underlying immune status in resource-poor countries.

PMID- 16101865
TI  - Determinants of genital wart case detection rates among STD clinic attendees in
      Athens, Greece.
AB  - BACKGROUND AND OBJECTIVE: To report significant sociodemographic and behavioral
      outpatient characteristics associated with the diagnosis of genital warts.
      METHODS: Cross-sectional hospital-based study (1990-96). RESULTS: Genital warts
      (n = 2988, 51.2%) represent the leading sexually transmitted disease (STD) among
      5831 consecutive symptomatic Greek and foreign immigrant STD outpatients. In
      Greek heterosexuals a low rate of partner change was the main patient
      characteristic at diagnosis (median: one partner in the past 6 months). Lower
      detection rate and riskier behavior characterized immigrants. Although associated
      with risky behavior, homo/bisexual orientation in males and injecting drug use
      were not significantly associated with condyloma diagnosis in the context of
      STDs. CONCLUSION: Broader health education and secondary prevention are needed to
      control this infection, whereas low-risk behavior in Greek heterosexuals with
      condylomata facilitates further preventive interventions.

PMID- 16101866
TI  - Benign cutaneous Degos disease.
AB  - A 24-year-old woman presented with an 8-year history of a recurrent asymptomatic
      rash characterized by small erythematous papules which evolved to form atrophic
      porcelain white scars with a telangectatic rim. She had never had
      gastrointestinal or neurological symptoms. A short trial of aspirin did not alter
      the behavior of the disease. Histology confirmed the clinical diagnosis of Degos
      disease. Degos disease is a rare disorder that has been classified into the
      benign or malignant variety. The malignant type has a poor prognosis.
      Gastrointestinal involvement is the most frequent cause of death. The existence
      of patients with a prolonged, purely cutaneous or benign form has been
      increasingly recognized. It may be impossible to classify a patient at the time
      of initial presentation. Her progress is consistent with the benign form.

PMID- 16101867
TI  - Serum interleukin-8 as a serologic marker of activity in Behcet's disease.
AB  - BACKGROUND: Immune dysregulation has been shown to be one of the major aspects of
      the yet unknown pathogenesis of Behcet's disease. Interleukin-8 (IL-8), a major
      chemokine with pivotal effects concerning leukocytes and endothelial cells, has
      been found to be elevated in patients with Behcet's disease. AIM: To evaluate the
      significance of elevated levels of IL-8 with respect to the activity of Behcet's
      disease. METHODS: Sixty-seven consecutive patients with Behcet's disease (37
      males, 30 females; 32.5 +/- 9.3 years) were enrolled in our study. The number of
      active clinical manifestations at the time of serum sampling was recorded. The
      degree of association between disease activity and IL-8, C-reactive protein, and
      erythrocyte sedimentation rate was assessed. RESULTS: Serum levels of IL-8
      increased as the number of clinically involved organs increased (P < 0.05). C
      reactive protein and the erythrocyte sedimentation rate showed no correlation
      with disease activity. CONCLUSIONS: Our study confirms that the IL-8 level is a
      more sensitive marker of disease activity than the erythrocyte sedimentation rate
      and C-reactive protein. It may be assumed that IL-8 plays an important role in
      the pathophysiology of Behcet's disease.

PMID- 16101868
TI  - Noma: an elegy to innocence and youth.

PMID- 16101869
TI  - Multiple minute digitate hyperkeratoses.

PMID- 16101870
TI  - Birt-Hogg-Dube Syndrome.
AB  - Birt-Hogg-Dube Syndrome is an autosomal dominant condition characterized by a
      triad of fibrofolliculomas, trichodiscomas, and acrochordons. Since the first
      description in 1977, many conditions have been described in association with its
      clinical triad. Recent epidemiological studies have shown a significant
      association between the occurrence of lesions in the
      fibrofolliculoma/trichodiscoma category with renal neoplasms and pneumothoracies.
      The BHD protein folliculin had recently been identified. The histological
      findings of the clinical lesions are distinctive. We report a patient with a
      history of melanoma who presented for routine surveillance. Facial lesions in the
      fibrofolliculoma/trichodiscoma category were identified. Diagnostic work-up
      revealed concomitant multinodular goiter, pulmonary cyst, and renal mass. The
      patient later developed pneumothorax. Clinical manifestations, histological
      findings, associations, management, and a review of the Birt-Hogg-Dube Syndrome
      are discussed.

PMID- 16101871
TI  - Branchio-oculo-facial syndrome with bilateral linear scars of the neck.
AB  - A case of branchio-oculo-facial syndrome with bilateral linear scars affecting
      both sides of the neck is described. The disease occured in a male patient aged
      20 years and presented with facial asymmetry, pre and postauricular pits, lip
      pits, microphthalmia, broad malformed nose, colobomas and dystrophic right
      kidney. In addition, there were bilateral linear hypertrophic scars on both sides
      of the neck. We believe that the latter lesions may represent the end stage of
      dermal thymus; a rare condition which has been reported so far in only four
      cases, two of which had branchio-oculo-facial syndrome.

PMID- 16101872
TI  - Concurrent Sweet's syndrome and leukemia cutis in patients with myeloid
      disorders.
AB  - A 74-year-old woman with chronic auricular fibrillation, arterial hypertension,
      hypercholesterolemia, ischemic cardiopathy, and peripheral arteriopathy presented
      with purpuric lesions on the lower limbs (Fig. 1) and, to a lesser extent, on the
      anterior area of the chest. The mucous membranes were not affected. In 1989, she
      was diagnosed with anemia that evolved until 1998, when a bone marrow biopsy
      revealed a myelodysplastic syndrome unclassified in French-American-British Group
      (FAB). The patient has required periodic transfusions since February 1999. A skin
      biopsy of the purpuric lesions revealed a leukocytoclastic vasculitis; the
      lesions cleared with topical corticosteroid treatment. In May 1999, the patient
      presented with inflammatory and painful lesions localized on the vulva (Fig. 2),
      which had evolved over several days, without fever. No lesions were observed in
      other locations. A cutaneous biopsy showed an intense dermal edema and a diffuse
      and polymorphous dermal infiltrate involving the follicular structures.
      Exocytosis, spongiosis, and mucin deposits, demonstrated by Alcian blue stain,
      were observed in the follicular epithelium. Mature neutrophils were predominant
      in the dermal infiltrate, but a small number of eosinophils and immature cells
      were also present (Fig. 3). The myelogenous origin of the immature lining cells
      was further confirmed by positive staining of intracytoplasmic granules with
      naphthol-ASD chloroacetate sterase (Leder's stain). Vasculitis was not observed.
      Routine laboratory tests revealed 3030 leukocytes/mm(3) (60% neutrophils), a
      hemoglobin level of 8.4 g/dL, and 92,000 platelets/mm(3). Treatment with 30
      mg/day of prednisone was started, and the lesions cleared slowly within 4 weeks.
      A new bone marrow biopsy in September 1999 showed a similar appearance to that
      taken in 1998. The patient died in January 2000 as a result of pneumonia with
      cardiac and respiratory failure. A 66-year-old man presented with a febrile
      syndrome that had evolved over 5 days, and painful and pruritic cutaneous lesions
      on the face and posterior neck (Fig. 4). Three months before, the patient was
      diagnosed with chronic myelogenous leukemia in acceleration phase. Examination
      revealed an edematous and erythematous face with pustular lesions on the surface,
      also involving the neck and the upper part of the back. The histopathologic
      examination revealed an intense edema and abscesses in the dermis. The infiltrate
      of these lesions was composed of mature neutrophils with the presence of abundant
      immature cells with a myelogenous aspect (Fig. 5). Analytical studies revealed
      26,130 leukocytes/mm(3) (42% blasts). No specific treatment for Sweet's syndrome
      was administered and the lesions showed an improvement within 5 days. Eight days
      after admission, the patient died as a result of acute hemorrhage, before
      treatment for leukemia was initiated.

PMID- 16101873
TI  - A case of allergic contact dermatitis from propylene glycol in an ultrasonic gel,
      sensitized at a leakage skin injury due to transcatheter arterial
      chemoembolization for hepatocellular carcinoma.
AB  - A 63-year-old man with hepatocellular carcinoma consequent to chronic viral
      hepatitis C presented with severe dermatitis on the lower right side of the back
      after transcatheter arterial chemoembolization (TACE) via the 10th intercostal
      artery, because his hepatic artery had already collapsed due to repeated usage
      for TACE. The regional skin showed redness and hardness with pustules.
      Histologically, there was epidermal and appendage necrosis, as well as exocytosis
      of red blood cells. With a diagnosis of skin injury due to leakage of lipiodol
      ultrafluid, mitomycin, and epirubicin, administered via the 10th intercostal
      artery, onto the skin tissue, topical application of 0.06% fluocinonide
      containing cream was prescribed. After several weeks of conservative local
      treatment, the leakage skin injury improved significantly, leaving pigmentation,
      hardness, and a small necrotic mass, as reported elsewhere (Honda T, Matsushima
      S, Fujii S, et al. A case of skin injury following transcatheter arterial
      chemotherapy through intercostal artery for hepatocellular carcinoma. Skin Res
      2003; 2: 18-22). Subsequently, the patient again consulted the Dermatology
      Department with further dermatitis in an almost identical skin region on the
      right side of the abdomen (irregularly spreading erythematous and edematous
      eruptions with itching; Fig. 1). As he had undergone an ultrasonic examination 2
      days earlier, allergic contact dermatitis from the ultrasonic gel was suspected.
      The contact dermatitis was treated with a topical corticosteroid hormone
      containing ointment. Patch testing was performed with Ultra Phonic Conductivity
      Gel (Pharmaceutical Innovations Inc., Newark, NJ, USA), with which the patient
      had undergone a series of ultrasonic examinations, and Sono Jelly (Toshiba
      Medical Supply Co., Ltd., Tokyo, Japan) as a reference, as well as white
      petroleum as a negative control. A positive result was obtained for Ultra Phonic
      Conductivity Gel, whereas Sono Jelly was negative (Fig. 2a). Pharmaceutical
      Innovations Inc. kindly supplied the ingredients of the gel: propylene glycol
      (PG), preservative in PG, color in PG, thickener 1, and thickener 2. The company
      gave no further details about the preservative, color, and thickeners. Patch
      testing was performed using these five materials, resulting in a positive
      reaction for PG, preservative in PG, and color in PG. Thickeners 1 and 2 and
      lipiodol ultrafluid were negative (Fig. 2b). On the assumption that the causative
      chemical was PG, commercially obtained PG, free of preservative and color, was
      then patch tested (original, 10% aqueous, 1% aqueous, and 0.1% aqueous
      solutions), resulting in original strongly positive, 10% positive, and 1% and
      0.1% weakly positive (Fig. 2c). The medical records showed that the patient had
      received 16 ultrasonic examinations with the same ultrasonic gel before the
      leakage skin injury. The 17th examination was performed 2 days after leakage
      dermatitis, and the 18th 3 months after the injury, when contact dermatitis
      occurred. The 19th examination was performed using Sono Jelly, which contains no
      PG, and no skin problems were observed.

PMID- 16101874
TI  - Effectiveness of kukui nut oil as a topical treatment for psoriasis.
AB  - BACKGROUND: No cure for psoriasis exists for the 1-3% of the American population
      who suffer from it; however, anecdotal reports from patients with psoriasis
      visiting Hawaii who purchased kukui nut oil, claim it helped reduce the severity
      of their lesions. OBJECTIVE: This pilot study was a double-blind, placebo
      controlled clinical trial to determine the effectiveness of kukui nut oil as a
      topical treatment for psoriasis. METHODS: Thirty adult subjects (18-78 year) were
      recruited from the community for a 12-week randomized, double-blind, placebo
      controlled pilot study. Subjects were previously diagnosed with mild, stable
      plaque psoriasis (less than 15% of total body surface area [TBSA]) and agreed to
      abstain from other treatments during the course of the study. Following a 4-week
      washout period the subjects were randomized into a treatment group (15 subjects
      applying kukui nut oil) or a control group (15 applying the mineral oil placebo).
      Patients were seen every 2 weeks (seven visits at 0, 2, 4, 6, 8, 10, and 12
      weeks) by a dermatological nurse practitioner under the general supervision of a
      board certified dermatologist. Measurable outcomes included evaluation of one
      targeted lesion and of the overall severity of their psoriasis using clinical
      evaluation, Psoriasis Area and Sensitivity Index (PASI), Global Severity of
      Psoriasis Scale, and photographs. Each patient also evaluated their own lesions
      daily using the Global Severity of Psoriasis Scale, and noted any side-effects or
      other treatments used. RESULTS: Although both groups improved, we found no
      significant difference between the treatment (kukui nut oil) and the placebo
      (mineral oil) among the 24 out of 30 subjects (80%) who completed the study. No
      side-effects or adverse events were reported. CONCLUSION: Kukui nut oil did not
      significantly reduce symptoms of psoriasis; however, this was a small pilot
      study, and the use of this oil cannot be dismissed without using a larger study
      population of patients with psoriasis.

PMID- 16101875
TI  - Etanercept and psoriasis, from clinical studies to real life.
AB  - OBJECTIVE: To determine whether etanercept therapy enables long-term psoriasis
      patients to discontinue systemic psoriatic therapy. METHODS: Charts from
      psoriatic patients on etanercept therapy seen at the Department of Dermatology
      and Dermatolgic Surgery, University of Miami, Miami, FL, USA, between June 2002
      and October 2003, were evaluated retrospectively. The duration of disease,
      adverse events to "standard" systemic psoriatic therapy, and current therapy were
      reviewed. IRB: 03/582C. RESULTS: A large proportion of patients (73.5%) were able
      to decrease or discontinue their traditional systemic agent while on etanercept.
      CONCLUSIONS: Etanercept is a safe and effective therapy in chronic moderate to
      severe psoriasis. In patients who are receiving systemic therapy for their
      disease and alternative therapy is warranted, etanercept can be added with the
      aim to discontinue the other systemic agents.

PMID- 16101876
TI  - Cyclosporine controls epidermolysis bullosa acquisita co-occurring with acquired
      factor VIII deficiency.
AB  - BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare antibody-mediated
      autoimmune blistering disease of adults. Likewise, acquired factor VIII
      deficiency is a rare antibody-mediated disease of adulthood. Both diseases can be
      exceedingly difficult to treat and refractory to immunomodulatory therapies.
      METHODS: Herein, we report a challenging case of EBA and acquired factor VIII
      deficiency in the same patient. RESULTS: Cyclosporine 4 mg/kg/day rapidly
      controlled both disease processes after the patient failed to respond to
      prednisone, colchicine, and pulse cyclophosphamide. The EBA relapsed when the
      cyclosporine was decreased to 2 mg/kg/day and the patient wore snuggly fitting
      new shoes, but it cleared quickly when the dose was increased. Cyclosporine has
      since been decreased gradually to 1.5 mg/kg/day without relapse of either
      condition or detectable side-effects. CONCLUSIONS: Cyclosporine should be
      considered when EBA and/or acquired factor VIII deficiency fail to respond to
      conservative therapy. Both conditions usually respond rapidly to cyclosporine 4-6
      mg/kg/day.

PMID- 16101877
TI  - Leprosy work and research in Oxford, UK: four decades in the pursuit of new
      knowledge about an arcane disease.

PMID- 16101878
TI  - Lepromatous leprosy and reversal reaction in a Micronesian immigrant.

PMID- 16101879
TI  - Worldwide skin diseases pattern.

PMID- 16101881
TI  - Actinic prurigo.

PMID- 16101883
TI  - Apocrine hidrocystoma: a case report and analysis of 167 Japanese cases.

PMID- 16101884
TI  - Nuchal fibroma clearly visualized by computed tomography: a case report.

PMID- 16101885
TI  - Skin diseases - clinical indicator of immune status in HIV infection.

PMID- 16101886
TI  - Noma (orofacial gangrene).

PMID- 16101891
TI  - Effect of calcitonin gene-related peptide on gonadotrophin-releasing hormone mRNA
      expression in GT1-7 cells.
AB  - Recent evidence has shown calcitonin gene-related peptide (CGRP) to be a key
      mediator of stress-induced suppression of the gonadotrophin-releasing hormone
      (GnRH) pulse generator, although little is known about the neural pathways
      involved. In the present study, we investigated the potential direct action of
      CGRP on GnRH neurones using GT1-7 cells, an established GnRH cell line. First, we
      detected expression of the CGRP receptor subunits, calcitonin receptor-like
      receptor and receptor activity-modifying protein-1 in the GT1-7 cells by reverse
      transcriptase-polymerase chain reaction. Second, we have shown that CGRP inhibits
      GnRH mRNA expression in the GT1-7 cells, which was effectively reversed by the
      CGRP receptor antagonist, CGRP8-37. These results suggest that CGRP down
      regulates expression of GnRH mRNA, via CGRP receptors in the GT1-7 cell, thus
      implying that a potential direct action of CGRP may mediate a suppressive effect
      on the GnRH neural network.

PMID- 16101892
TI  - Inhibiting biosynthesis and/or metabolism of progestins in the ventral tegmental
      area attenuates lordosis of rats in behavioural oestrus.
AB  - In the ventral tegmental area (VTA), lordosis of rats is facilitated by 5alpha
      pregnan-3alpha-ol-20-one (3alpha,5alpha-THP). Central 3alpha,5alpha-THP results
      from metabolism of peripheral progesterone, from the ovaries and/or adrenals, by
      sequential enzymatic activity of 5alpha-reductase and 3alpha-hydroxysteroid
      oxidoreductase (3alpha-HSOR). In addition, in glial cells, cholesterol is
      converted into pregnenolone by the P450 side-chain cleavage enzyme (P450scc),
      which is then metabolized to progesterone by 3beta-hydroxysteroid dehydrogenase,
      and subsequently reduced to 3alpha,5alpha-THP. We hypothesize that, in the VTA,
      formation of 3alpha,5alpha-THP by both metabolism and biosynthesis is necessary
      for facilitation of lordosis of female rats. In Experiment 1, naturally-receptive
      rats received bilateral VTA infusions of a P450scc inhibitor, digitoxin (1
      microg/side); a 5alpha-reductase inhibitor, finasteride (10 microg/side);
      digitoxin (1 microg/side)+finasteride (10 microg/side); or vehicle and were
      tested 3 h later for lordosis. In Experiment 2, the effects of VTA infusions of
      digitoxin, finasteride, digitoxin+finasteride, or vehicle on lordosis and
      midbrain and plasma 3alpha,5alpha-THP levels were examined. In Experiment 3, we
      investigated whether infusions of 3alpha,5alpha-THP to the VTA reinstated
      lordosis and midbrain 3alpha,5alpha-THP levels following administration of
      inhibitors. VTA infusions of digitoxin, finasteride, or digitoxin+finasteride,
      significantly and similarly reduced lordosis and midbrain, but not plasma
      3alpha,5alpha-THP levels, compared to vehicle. Following receipt of inhibitor
      infusions, 3alpha,5alpha-THP to the VTA restored lordosis and midbrain
      3alpha,5alpha-THP levels. These data suggest that, in the VTA, both central
      biosynthesis of progesterone and metabolism of progesterone (from central and/or
      peripheral sources) to 3alpha,5alpha-THP are important for mediating lordosis of
      rats.

PMID- 16101893
TI  - Interactions between kinases and phosphatases in the rapid control of brain
      aromatase.
AB  - Aromatization of testosterone into oestradiol plays a key role in the activation
      of male sexual behaviour in many vertebrate species. Rapid changes in brain
      aromatase activity have recently been identified and the resulting changes in
      local oestrogen bioavailability could modulate fast behavioural responses to
      oestrogens. In quail hypothalamic homogenates, aromatase activity is down
      regulated within minutes by calcium-dependent phosphorylations in the presence of
      ATP, MgCl2 and CaCl2 (ATP/Mg/Ca). Three kinases (protein kinases A and C and
      calmodulin kinase; PKA, PKC and CAMK) are potentially implicated in this process.
      If kinases decrease aromatase activity in a reversible manner, then it would be
      expected that the enzymatic activity would increase and/or return to baseline
      levels in the presence of phosphatases. We showed previously that 0.1 mM vanadate
      (a general inhibitor of protein phosphatases) significantly decreases aromatase
      activity but specific protein phosphatases that could up-regulate aromatase
      activity have not been identified to date. The reversibility of aromatase
      activity inhibition by phosphorylations was investigated in the present study
      using alkaline and acid phosphatase (Alk and Ac PPase). Unexpectedly, Alk PPase
      inhibited aromatase activity in a dose-dependent manner in the presence, as well
      as in the absence, of ATP/Mg/Ca. By contrast, Ac PPase completely blocked the
      inhibitory effects of ATP/Mg/Ca on aromatase activity, even if it moderately
      inhibited aromatase activity in the absence of ATP/Mg/Ca. However, the addition
      of Ac PPase was unable to restore aromatase activity after it had been inhibited
      by exposure to ATP/Mg/Ca. Taken together, these data suggest that, amongst the 15
      potential consensus phosphorylation sites identified on the quail aromatase
      sequence, some must be constitutively phosphorylated for the enzyme to be active
      whereas phosphorylation of the others is involved in the rapid inhibition of
      aromatase activity by the competitive effects of protein kinases and
      phosphatases. Two out of these 15 putative phosphorylation sites occur in an
      environment corresponding to the consensus sites for PKC, PKA (and possibly a
      CAMK) and, in all probability, represent the sites whose phosphorylation rapidly
      blocks enzyme activity.

PMID- 16101894
TI  - Testosterone regulates androgen receptor immunoreactivity in the copulatory, but
      not courtship, neuromuscular system in adult male green anoles.
AB  - Androgens regulate the expression of male reproductive behaviour in diverse
      vertebrate species, often acting on androgen receptors (AR) to induce structural
      or functional changes in the nervous system and periphery. Male green anoles
      possess two sexually dimorphic neuromuscular systems, one controlling throat fan
      (dewlap) extension, which occurs during courtship, and the other mediating
      copulatory organ function. Although androgens are required for behavioural
      activation in both systems, testosterone has differential effects on the
      neuromuscular morphology. It increases the size of copulatory muscle fibres
      during the breeding season, but significant effects on dewlap muscle fibre size
      and motoneurone soma size in either system have not been detected. Corresponding
      to the lack of testosterone-induced morphological effects in the courtship
      system, relatively low levels of AR are expressed in the associated motoneurones.
      The present experiment had two goals, aiming to determine whether: (i) the other
      courtship and copulatory neuromuscular tissues express AR and (ii) testosterone
      and/or seasonal environmental changes regulate AR expression. The percentage of
      AR+ nuclei was evaluated in both the breeding and nonbreeding seasons in
      gonadally intact adult males (Experiment 1) and in castrated males treated with
      either testosterone or vehicle (Experiment 2). AR was extensively expressed in
      the dewlap and copulatory muscles, and in a high percentage of the copulatory
      motoneurones, but immunoreactivity did not vary across season. Testosterone
      increased the percentage of AR+ nuclei in the copulatory muscles of both breeding
      and nonbreeding males but not in the dewlap muscle or copulatory motoneurones.
      Finally, the target structures for both systems (cartilages and hemipenes)
      expressed AR in all animals. Therefore, the effects of testosterone on AR
      immunoreactivity suggest that up-regulation of the receptors may be important for
      morphological change. However, because all structures investigated in the present
      experiment expressed AR, the data also indicate that the receptors are involved
      with other functions.

PMID- 16101895
TI  - Ghrelin-induced stimulation of colonic propulsion is dependent on hypothalamic
      neuropeptide Y1- and corticotrophin-releasing factor 1 receptor activation.
AB  - Peptides participating in the hypothalamic control of feeding behaviour are also
      involved in the central autonomic control of gastrointestinal functions, such as
      secretion and motility. An anatomical interaction and functional relationship in
      the central nervous system between the feeding-related peptides neuropeptide Y
      and ghrelin is well documented. Furthermore, it has been shown that feeding
      related peptides can influence digestive function via central corticotrophin
      releasing factor (CRF) pathways. In the present study, we investigated the role
      of ghrelin in the central autonomic control of colonic motility. Furthermore, we
      addressed the hypothesis that ghrelin is involved in the hypothalamic control of
      colonic motor function, utilizing central neuropeptide Y receptors and
      hypothalamic CRF pathways. Ghrelin (0.03, 0.06 and 0.12 nmol) bilaterally
      microinjected into the paraventricular nucleus (PVN) induced a significant
      stimulation of colonic propulsion. In particular, the colonic transit time
      decreased from 312+/-7 min to 198+/-12 min. Microinjection of the neuropeptide Y1
      receptor antagonist, BIBP-3226 (200 pmol), or the nonselective CRF receptor
      antagonist, astressin (30 pmol), into the PVN abolished the stimulatory effect of
      ghrelin injected into the PVN on colonic transit time, whereas pretreatment with
      the selective CRF2 receptor, antisauvagine-30 (28 pmol), failed to affect the
      effect of PVN-ghrelin injection on colonic propulsion. These results suggest that
      ghrelin can act as central modulator of gastrointestinal motor functions at the
      level of the PVN via neuropeptide Y1- and CRF1 receptor-dependent mechanisms.

PMID- 16101896
TI  - Differential contribution of nitric oxide and cGMP to the stimulatory effects of
      growth hormone-releasing hormone and low-concentration somatostatin on growth
      hormone release from somatotrophs.
AB  - There is increasing evidence that nitric oxide (NO) produced by NO synthase
      (NOS), and their signalling partners, guanylyl cyclase and cGMP, play a relevant
      role in growth hormone (GH) secretion from somatotrophs. We previously
      demonstrated that both GH-releasing hormone (GHRH; 10(-8) M) and low
      concentrations of somatostatin (10(-15) M) stimulate pig GH release in vitro,
      whereas a high somatostatin concentration (10(-7) M) inhibits GHRH-induced GH
      secretion. To ascertain the possible contribution of the NOS-NO and guanylyl
      cyclase-cGMP routes to these responses, cultures of pituitary cells from
      prepubertal female pigs were treated (30 min) with GHRH (10(-8) M) or
      somatostatin (10(-7) or 10(-15) M) in the absence or presence of activators or
      blockers of key steps of these signalling cascades, and GH release was measured.
      Two distinct activators of NO route, SNAP (5x10(-4) M) or L-AME (10(-3) M),
      similarly stimulated GH release when applied alone (with this effect being
      blocked by 10(-7) M somatostatin), but did not alter the stimulatory effect of
      GHRH or 10(-15) M somatostatin. Conversely, two NO pathway inhibitors, NAME (10(
      5) M) or haemoglobin (20 microg/ml) similarly blocked GHRH- or 10(-15) M
      somatostatin-stimulated GH release. 8-Br-cGMP (10(-8) to 10(-4) M) strongly
      stimulated GH release, suggesting that cGMP may function as a subsequent step in
      the NO pathway in this system. Interestingly, 10(-7) M somatostatin did not
      inhibit the stimulatory effect of 8-Br-cGMP. Moreover, although 8-Br-cGMP did not
      modify the effect of GHRH, it enhanced GH release stimulated by 10(-15) M
      somatostatin. Accordingly, a specific guanylyl cyclase inhibitor, LY-83, 583 (10(
      5) M) did not alter 10(-15) M somatostatin-induced GH release, whereas it blocked
      GHRH-induced GH secretion. These results demonstrate for the first time that the
      NOS/NO signalling pathway contributes critically to the stimulatory effects of
      both GHRH and low-concentration somatostatin on GH release, and that, conversely,
      the subsequent guanylyl cyclase/cGMP step only mediates GHRH- and not low
      concentration somatostatin-induced GH secretion from somatotrophs.

PMID- 16101897
TI  - Micro-opioid receptor preferentially inhibits oxytocin release from
      neurohypophysial terminals by blocking R-type Ca2+ channels.
AB  - Oxytocin release from neurophypophysial terminals is particularly sensitive to
      inhibition by the micro-opioid receptor agonist, DAMGO. Because the R-type
      component of the neurophypophysial terminal Ca2+ current (ICa) mediates
      exclusively oxytocin release, we hypothesised that micro-opioids could
      preferentially inhibit oxytocin release by blocking this channel subtype. Whole
      terminal recordings showed that DAMGO and the R-type selective blocker SNX-482
      inhibit a similar ICa component. Measurements of [Ca2+]i levels and oxytocin
      release confirmed that the effects of DAMGO and SNX-482 are not additive.
      Finally, isolation of the R-type component and its associated rise in [Ca2+]i and
      oxytocin release allowed us to demonstrate the selective inhibition by DAMGO of
      this channel subtype. Thus, micro-opioid agonists modulate specifically oxytocin
      release in neurophypophysial terminals by selectively targeting R-type Ca2+
      channels. Modulation of Ca2+ channel subtypes could be a general mechanism for
      drugs of abuse to regulate the release of specific neurotransmitters at central
      nervous system synapses.

PMID- 16101898
TI  - Developmental changes in GABA receptor subunit composition within the
      gonadotrophin-releasing hormone-1 neuronal system.
AB  - It is becoming increasingly evident that GABA plays an important role in the
      regulation of gonadotrophin-releasing hormone (GnRH)-1 neurones via the GABAA
      receptor. The aim of the present study was to characterise expression of the
      GABAA receptor within the GnRH-1 system across development. The expression
      pattern of five GABAAalpha subunits and one GABAAbeta subunit was first examined
      within individual GnRH-1 neurones by the polymerase chain reaction. A significant
      increase in the expression of GABAAalpha2 and a significant decrease in the
      expression of GABAAalpha6 over time were found. Of the other subunits examined,
      two (alpha1 and alpha3) showed no differences in expression and two (alpha4 and
      beta3) showed variable low incidence of expression. Given the reciprocal
      relationship of alpha2 and alpha6 expression, we hypothesised that there is a
      developmental switch in the expression of these subunits in GnRH-1 neurones. To
      investigate this hypothesis, single- and double-label immunocytochemistry for
      GABAAalpha2 and alpha6 and GnRH-1 was performed in tissue from ages E12.5 to
      adulthood, as well as in nasal explants. We show that GABAAalpha2 and alpha6 are
      present in the GnRH-1 neuronal system both in vivo and in vitro and that the
      levels of expression are altered as a function of age.

PMID- 16101899
TI  - Chronic prenatal ethanol exposure alters glucocorticoid signalling in the
      hippocampus of the postnatal Guinea pig.
AB  - The present study tested the hypothesis that chronic prenatal ethanol exposure
      causes long-lasting changes in glucocorticoid signalling in postnatal offspring.
      Pregnant guinea pigs were treated with ethanol (4 g/kg maternal body weight/day),
      isocaloric-sucrose/pair-feeding or water throughout gestation, and maternal
      saliva cortisol concentration was determined 2 h after treatment at different
      stages of gestation. Electrically-stimulated release of glutamate and GABA, in
      the presence or absence of dexamethasone, as well as glucocorticoid and
      mineralocorticoid receptor mRNA expression, was determined in the hippocampus and
      prefrontal cortex of adult offspring of treated pregnant guinea pigs. Maternal
      saliva cortisol concentration increased throughout pregnancy, which was
      associated with increased foetal plasma and amniotic fluid cortisol
      concentration. Ethanol administration to pregnant guinea pigs increased maternal
      saliva cortisol concentration during early and mid-gestation. In late gestation,
      ethanol administration did not increase saliva cortisol concentration above that
      induced by pregnancy. Chronic prenatal ethanol exposure had no effect on
      stimulated glutamate or GABA release, but selectively prevented dexamethasone
      mediated suppression of stimulated glutamate release, and decreased expression of
      mineralocorticoid, but not glucocorticoid, receptor mRNA in the hippocampus of
      adult offspring. These data indicate that maternal ethanol administration leads
      to excessively increased maternal cortisol concentration that can impact
      negatively the developing foetal brain, leading to persistent postnatal deficits
      in glucocorticoid regulation of glutamate signalling in the adult hippocampus.

PMID- 16101900
TI  - Cannabinoids modulate synaptic activity in the rat supraoptic nucleus.
AB  - In the present study, we investigated the effects of the cannabinoid receptor
      agonist CP55,940 on excitatory and inhibitory synaptic transmission in the rat
      supraoptic nucleus. Whole-cell patch clamp recordings were performed on
      supraoptic neurones in in vitro brain slice preparations. CP55,940 significantly
      reduced the frequency of spontaneous excitatory and inhibitory postsynaptic
      currents in a concentration-dependent manner. These changes were potently
      reversed by the CB1 receptor antagonist AM251. The results indicate that
      cannabinoids modulate the activity of magnocellular neurosecretory neurones by
      presynaptic inhibition of both excitatory and inhibitory synaptic transmission.

PMID- 16101902
TI  - Mycorrhizal fungi and environmental change: the need for a mycocentric approach.

PMID- 16101903
TI  - Global environmental change and the uncertain fate of biodiversity. Global
      Environmental Change and Biodiversity--a DIVERSITAS/Tyndall Centre/TERACC/QUEST
      sponsored workshop, Dourdan, France, May 2005.

PMID- 16101904
TI  - A reinterpretation of the earliest quantification of global plant productivity by
      von Liebig (1862).

PMID- 16101905
TI  - Genes and salt tolerance: bringing them together.
AB  - Salinity tolerance comes from genes that limit the rate of salt uptake from the
      soil and the transport of salt throughout the plant, adjust the ionic and osmotic
      balance of cells in roots and shoots, and regulate leaf development and the onset
      of senescence. This review lists some candidate genes for salinity tolerance, and
      draws together hypotheses about the functions of these genes and the specific
      tissues in which they might operate. Little has been revealed by gene expression
      studies so far, perhaps because the studies are not tissue-specific, and because
      the treatments are often traumatic and unnatural. Suggestions are made to
      increase the value of molecular studies in identifying genes that are important
      for salinity tolerance.

PMID- 16101906
TI  - In the light of stomatal opening: new insights into 'the Watergate'.
AB  - Stomata can be regarded as hydraulically driven valves in the leaf surface, which
      open to allow CO2 uptake and close to prevent excessive loss of water. Movement
      of these 'Watergates' is regulated by environmental conditions, such as light,
      CO2 and humidity. Guard cells can sense environmental conditions and function as
      motor cells within the stomatal complex. Stomatal movement results from the
      transport of K+ salts across the guard cell membranes. In this review, we discuss
      the biophysical principles and mechanisms of stomatal movement and relate these
      to ion transport at the plasma membrane and vacuolar membrane. Studies with
      isolated guard cells, combined with recordings on single guard cells in intact
      plants, revealed that light stimulates stomatal opening via blue light-specific
      and photosynthetic-active radiation-dependent pathways. In addition, guard cells
      sense changes in air humidity and the water status of distant tissues via the
      stress hormone abscisic acid (ABA). Guard cells thus provide an excellent system
      to study cross-talk, as multiple signaling pathways induce both short- and long
      term responses in these sensory cells.

PMID- 16101907
TI  - Evolution of leaf developmental mechanisms.
AB  - Leaves are determinate organs produced by the shoot apical meristem. Land plants
      demonstrate a large range of variation in leaf form. Here we discuss evolution of
      leaf form in the context of our current understanding of leaf development, as
      this has emerged from molecular genetic studies in model organisms. We also
      discuss specific examples where parallel studies of development in different
      species have helped understanding how diversification of leaf form may occur in
      nature.

PMID- 16101908
TI  - Microtubules guide root hair tip growth.
AB  - The ability to establish cell polarity is crucial to form and function of an
      individual cell. Polarity underlies critical processes during cell development,
      such as cell growth, cell division, cell differentiation and cell signalling.
      Interphase cytoplasmic microtubules in tip-growing fission yeast cells have been
      shown to play a particularly important role in regulating cell polarity. By
      placing proteins that serve as spatial cues in the cell cortex of the expanding
      tip, microtubules determine the site where exocytosis, and therefore growth,
      takes place. Transport and the targeting of exocytotic vesicles to the very tip
      depend on the actin cytoskeleton. Recently, endoplasmic microtubules have been
      identified in tip-growing root hairs, which are an experimental system for plant
      cell growth. Here, we review the data that demonstrate involvement of
      microtubules in hair elongation and polarity of the model plants Medicago
      truncatula and Arabidopsis thaliana. Differences and similarities between the
      microtubule organization and function in these two species are discussed and we
      compare the observations in root hairs with the microtubule-based polarity
      mechanism in fission yeast.

PMID- 16101909
TI  - The morphogenesis of lobed plant cells in the mesophyll and epidermis:
      organization and distinct roles of cortical microtubules and actin filaments.
AB  - The morphogenesis of lobed plant cells has been considered to be controlled by
      microtubule (MT) and/or actin filament (AF) organization. In this article, a
      comprehensive mechanism is proposed, in which distinct roles are played by these
      cytoskeletal components. First, cortical MT bundles and, in the case of pavement
      cells, radial MT arrays combined with MT bundles determine the deposition of
      local cell wall thickenings, the cellulose microfibrils of which copy the
      orientation of underlying MTs. Cell growth is thus locally prevented and,
      consequently, lobes and constrictions are formed. Arch-like tangential expansion
      is locally imposed at the external periclinal wall of pavement cells by the
      radial arrangement of cellulose microfibrils at every wall thickening. Whenever
      further elongation of the original cell lobes occurs, AF patches assemble at the
      tips of growing lobes. Intercellular space formation is promoted or prevented by
      the opposite or alternate, respectively, arrangement of cortical MT arrays
      between neighboring cells. The genes that are possibly involved in the molecular
      regulation of the above morphogenetic procedure by MT and AF array organization
      are reviewed.

PMID- 16101910
TI  - Managing the manganese: molecular mechanisms of manganese transport and
      homeostasis.
AB  - Manganese (Mn) is an essential metal nutrient for plants. Recently, some of the
      genes responsible for transition metal transport in plants have been identified;
      however, only relatively recently have Mn2+ transport pathways begun to be
      identified at the molecular level. These include transporters responsible for Mn
      accumulation into the cell and release from various organelles, and for active
      sequestration into endomembrane compartments, particularly the vacuole and the
      endoplasmic reticulum. Several transporter gene families have been implicated in
      Mn2+ transport, including cation/H+ antiporters, natural resistance-associated
      macrophage protein (Nramp) transporters, zinc-regulated transporter/iron
      regulated transporter (ZRT/IRT1)-related protein (ZIP) transporters, the cation
      diffusion facilitator (CDF) transporter family, and P-type ATPases. The
      identification of mutants with altered Mn phenotypes can allow the identification
      of novel components in Mn homeostasis. In addition, the characterization of Mn
      hyperaccumulator plants can increase our understanding of how plants can adapt to
      excess Mn, and ultimately allow the identification of genes that confer this
      stress tolerance. The identification of genes responsible for Mn2+ transport has
      substantially improved our understanding of plant Mn homeostasis.

PMID- 16101911
TI  - Mosaicism in the organization of Con A binding sites on the membrane surface of
      female cells of Nicotiana tabacum.
AB  - The presence of mosaicism in the organization of concanavalin agglutinin (Con A)
      binding sites on murine egg cells was first reported 30 year ago. This discovery
      has triggered extensive studies into the roles of glycoproteins in gamete
      interactions in animals. This report comprises the first account of the existence
      of the mosaicism in higher plants. The distribution of Con A binding sites on
      both egg cells and central cells of tobacco (Nicotiana tabacum) was found to be
      polar and apparently determined by the location of the nucleus of the cell. On
      central cells, Con A binding sites were distributed on the section of the plasma
      membrane surface near the nucleus. By contrast, the binding sites on egg cells
      were concentrated away from the nucleus. Therefore, polarity of the plasma
      membrane component of female cells was confirmed for the first time. It is
      proposed that such polarized ConA binding sites could be involved in sperm
      recognition.

PMID- 16101912
TI  - Assessment of penetrance and expressivity of RNAi-mediated silencing of the
      Arabidopsis phytoene desaturase gene.
AB  - RNA interference (RNAi) is of great value in plant functional genomics. However,
      the absence of RNAi phenotypes and the lack of uniform level of RNAi silencing
      has complicated gene identification. Here, the penetrance and expressivity of
      RNAi-mediated silencing of the phytoene desaturase (PDS) gene in Arabidopsis
      thaliana were examined quantitatively to provide a reference for the likely
      severity and distribution of silencing effects. Arabidopsis plants were
      transformed with an RNAi construct targeting PDS. Transgenic plants were examined
      for frequency of RNAi-mediated silencing and various silencing phenotypes. mRNA
      depletion level and RNAi expressivity were assayed by relative reverse
      transcription polymerase chain reaction (RT-PCR). High penetrance and variable
      expressivity of RNAi were demonstrated. An inverse correlation between PDS mRNA
      level and RNAi phenotype was seen. No direct relationship between copy number for
      the RNAi-generating transgene and phenotype was evident. Decreased RNAi
      penetrance in T2 plants was observed. It is suggested that variability in RNAi
      expressivity and postmeiotic decrease in RNAi penetrance constitute barriers for
      high throughput plant gene characterization.

PMID- 16101913
TI  - Gradients of lipid storage, photosynthesis and plastid differentiation in
      developing soybean seeds.
AB  - This study establishes a topographical framework for functional investigations on
      the regulation of lipid biosynthesis and its interaction with embryo
      photosynthesis in developing soybean seed. Structural observations, combined with
      molecular and functional parameters, revealed the gradual transformation of
      chloroplasts into storage organelles, starting from inner regions going outwards.
      This is evidenced by electron microscopy, confocal laser scanning microscopy, in
      situ hybridization and histochemical/biochemical data. As a consequence of
      plastid differentiation, photosynthesis becomes distributed along a gradient
      within the developing embryo. Electron transport rate, effective quantum yield
      and O2 production rate are maximal in the embryo periphery, as documented by
      imaging pulse-amplitude-modulated fluorescence and O2 release via microsensors.
      The gradual loss of photosynthetic capacity was accompanied by a similarly
      gradual accumulation of starch and lipids. Noninvasive nuclear magnetic resonance
      spectroscopy of mature seeds revealed steep gradients in lipid deposition, with
      the highest concentrations in inner regions. The inverse relationship between
      photosynthesis and lipid biosynthesis argues against a direct metabolic
      involvement of photosynthesis in lipid biosynthesis during the late storage
      stage, but points to a role for photosynthetic oxygen release. This hypothesis is
      verified in a companion paper.

PMID- 16101914
TI  - Evidence of a key role for photosynthetic oxygen release in oil storage in
      developing soybean seeds.
AB  - Based on the topographical analysis of photosynthesis and oil storage, we propose
      in a companion paper that photosynthetic oxygen release plays a key role in the
      local energy state, storage metabolism and flux toward lipid biosynthesis in
      developing soybean seeds. To test this hypothesis, we combined topographical
      analysis of ATP gradients across tissues, microsensor quantifications of internal
      O2 levels, assays of energy balance, metabolite profiles and isotope-labelling
      studies. Seeds show a marked degree of oxygen starvation in vivo (minimum O2
      levels 0.1 kPa, approximately 1.3 microm), affecting ATP gradients, overall
      energy state, metabolite pools and storage activity. Despite the low light
      availability, photosynthesis supplies significant amounts of oxygen to the
      hypoxic seed tissue. This is followed by an increase in local ATP levels, most
      prominently within the lipid-synthesizing (inner) regions of the embryo.
      Concomitantly, partitioning of 14C-sucrose to lipids is increased, suggesting
      higher rates of lipid biosynthesis. It is concluded that both respiratory and
      biosynthetic fluxes are dynamically adjusted to photosynthetic oxygen supply.

PMID- 16101915
TI  - Resistance cost of a cytochrome P450 herbicide metabolism mechanism but not an
      ACCase target site mutation in a multiple resistant Lolium rigidum population.
AB  - Costs of resistance are predicted to reduce plant productivity in herbicide
      resistant weeds. Lolium rigidum herbicide-susceptible individuals (S),
      individuals possessing cytochrome P450-based herbicide metabolism (P450) and
      multiple resistant individuals possessing a resistant ACCase and enhanced
      cytochrome P450 metabolism (ACCase/P450) were grown in the absence of mutual
      plant interaction to estimate plant growth traits. Both P450 and ACCase/P450
      resistant phenotypes produced less above-ground biomass than the S phenotype
      during the vegetative stage. Reduced biomass production in the resistant
      phenotypes corresponded to a reduced relative growth rate and a lower net
      assimilation rate and rate of carbon fixation. There were no significant
      differences between the two resistant phenotypes, suggesting that costs of
      resistance are associated with P450 metabolism-based resistance. There were no
      differences in reproductive output among the three phenotypes, indicating that
      the cost of P450 resistance during vegetative growth is compensated during the
      production of reproductive structures. The P450-based herbicide metabolism is
      shown to be associated with physiological resistance costs, which may be
      manipulated by agronomic management to reduce the evolution of herbicide
      resistance.

PMID- 16101916
TI  - Silicon uptake and transport is an active process in Cucumis sativus.
AB  - Cucumis sativus is a species known to accumulate high levels of silicon (Si) in
      the tops, though the mechanism for its high Si uptake is little understood. In a
      series of hydroponic experiments, we examined uptake and xylem loading of Si in
      C. sativus along with Vicia faba at three levels of Si (0.085, 0.17 and 1.70 mm).
      Measured Si uptake in C. sativus was more than twice as high as calculated from
      the rate of transpiration assuming no discrimination between silicic acid and
      water in uptake. Measured Si uptake in V. faba, however, was significantly lower
      than the calculated uptake. Concentration of Si in xylem exudates was several
      fold higher in C. sativus, but was significantly lower in V. faba compared with
      the Si concentration in external solutions, regardless of Si levels. Silicon
      uptake was strongly inhibited by low temperature and 2,4-dinitrophenol, a
      metabolic inhibitor, in C. sativus but not in V. faba. It can be concluded that
      Si uptake and transport in C. sativus is active and independent of external Si
      concentrations, in contrast to the process in V. faba.

PMID- 16101917
TI  - Cadmium hyperaccumulation protects Thlaspi caerulescens from leaf feeding damage
      by thrips (Frankliniella occidentalis).
AB  - Metal hyperaccumulation has been proposed as a plant defensive strategy. Here, we
      investigated whether cadmium (Cd) hyperaccumulation protected Thlaspi
      caerulescens from leaf feeding damage by thrips (Frankliniella occidentalis). Two
      ecotypes differing in Cd accumulation, Ganges (high) and Prayon (low), were grown
      in compost amended with 0-1000 mg Cd kg(-1) in two experiments under glasshouse
      conditions. F2 and F3 plants from the Prayon x Ganges crosses were grown with 5
      mg Cd kg(-1). Plants were naturally colonized by thrips and the leaf feeding
      damage index (LFDI) was assessed. The LFDI decreased significantly with
      increasing Cd in both ecotypes, and correlated with shoot Cd concentration in a
      log-linear fashion. Prayon was more attractive to thrips than Ganges, but the
      ecotypic difference in the LFDI was largely accounted for by the shoot Cd
      concentration. In the F2 and F3 plants, the LFDI correlated significantly and
      negatively with shoot Cd, but not with shoot zinc (Zn) or sulphur (S)
      concentrations. We conclude that Cd hyperaccumulation deters thrips from feeding
      on T. caerulescens leaves, which may offer an adaptive benefit to the plant.

PMID- 16101918
TI  - Sap flow rates and sapwood density are critical factors in within- and between
      tree variation in CO2 efflux from stems of mature Dacrydium cupressinum trees.
AB  - Measurements of CO2 efflux from stems and branches, sap velocity, and respiratory
      activity of excised wood cores were conducted in Dacrydium cupressinum trees that
      differed in diameter, age, and canopy emergence. The objective of this study was
      to determine if consistent linkages exist among respiratory production of CO2
      within stems, xylem transport of CO2, and the rate of CO2 diffusing from stem
      surfaces. Stem CO2 efflux was depressed during periods of sap flow compared with
      the efflux rate expected for a given stem temperature and was positively
      correlated with sapwood density. By contrast, no significant relationships were
      observed between CO2 efflux and the respiratory activity of wood tissues. Between
      86 and 91% of woody tissue respiration diffused to the atmosphere over a 24-h
      period. However, at certain times of the day, xylem transport and internal
      storage of CO2 may account for up to 13-38% and 12-18%, respectively, of woody
      tissue respiration. These results demonstrate that differences in sap flow rates
      and xylem anatomy are critically important for explaining within- and between
      tree variation in CO2 efflux from stems.

PMID- 16101919
TI  - Canopy and environmental control of root dynamics in a long-term study of Concord
      grape.
AB  - Below-ground carbon allocation represents a substantial fraction of net
      photosynthesis in plants, yet timing of below-ground allocation and endogenous
      and exogenous factors controlling it are poorly understood. Minirhizotron
      techniques were used to examine root populations of Vitis labruscana Bailey cv.
      Concord under two levels of dormant-season canopy removal and irrigation. Root
      production, pigmentation, death and disappearance to a depth of 110 cm were
      determined over two wet and two dry years (1997-2000). There was continual root
      production and senescence, with peak root production rates occurring by
      midseason. Later in the season, when reproductive demands for carbon were highest
      and physical conditions limiting, few roots were produced, especially in dry
      years in nonirrigated vines. Root production under minimal canopy pruning was
      generally greater and occurred several weeks earlier than root production under
      heavy pruning, corresponding to earlier canopy development. Initial root
      production occurred in shallow soils, likely due to temperatures at shallow
      depths being warmer early in the season. Our study showed intricate relationships
      between internal carbon demands and environmental conditions regulating root
      allocation.

PMID- 16101920
TI  - Patterns of variability in the diameter of lateral roots in the banana root
      system.
AB  - The relative importance of root system structure, plant carbon status and soil
      environment in the determination of lateral root diameter remains unclear, and
      was investigated in this study. Banana (Musa acuminata) plants were grown at
      various moderate levels of soil compaction in two distinct experiments, in a
      field experiment (FE) and in a glasshouse experiment (GE). Radiant flux density
      was 5 times lower in GE. The distribution of root diameter was measured for
      several root branching orders. Root diameters ranged between 0.09 and 0.52 mm for
      secondary roots and between 0.06 and 0.27 mm for tertiary roots. A relationship
      was found between the diameter of the parent bearing root and the median diameter
      of its laterals, which appears to be valid for a wide range of species. Mean
      lateral root diameter increased with distance to the base of the root and
      decreased with branching density [number of lateral roots per unit length of
      bearing root (cm(-1))]. Typical symptoms of low light availability were observed
      in GE. In this case, lateral root diameter variability was reduced. Although
      primary root growth was affected by soil compaction, no effects on lateral root
      diameter were observed.

PMID- 16101921
TI  - Caterpillars of Euphydryas aurinia (Lepidoptera: Nymphalidae) feeding on Succisa
      pratensis leaves induce large foliar emissions of methanol.
AB  - A major new discovery made in the last decade is that plants commonly emit large
      amounts and varieties of volatiles after damage inflicted by herbivores, and not
      merely from the site of injury. However, analytical methods for measuring
      herbivore-induced volatiles do not usually monitor the whole range of these
      compounds and are complicated by the transient nature of their formation and by
      their chemical instability. Here we present the results of using a fast and
      highly sensitive proton transfer reaction-mass spectrometry (PTR-MS) technique
      that allows simultaneous on-line monitoring of leaf volatiles in the pptv (pmol
      mol(-1)) range. The resulting on-line mass scans revealed that Euphydryas aurinia
      caterpillars feeding on Succisa pratensis leaves induced emissions of huge
      amounts of methanol--a biogeochemically active compound and a significant
      component of the volatile organic carbon found in the atmosphere--and other
      immediate, late and systemic volatile blends (including monoterpenes,
      sesquiterpenes and lipoxygenase-derived volatile compounds). In addition to
      influencing neighboring plants, as well as herbivores and their predators and
      parasitoids, these large emissions might affect atmospheric chemistry and physics
      if they are found to be generalized in other plant species.

PMID- 16101922
TI  - Taking mycocentrism seriously: mycorrhizal fungal and plant responses to elevated
      CO2.
AB  - The aim here was to separately assess mycorrhizal fungal and plant responses
      under elevated atmospheric CO2, and to test a mycocentric model that assumes that
      increased carbon availability to the fungus will not automatically feed back to
      enhanced plant growth performance. Meta-analyses were applied across independent
      studies. Responses were compared in ectomycorrhizal (ECM) and arbuscular
      mycorrhizal (AM) fungi, and ECM and AM plants. Responses of both mycorrhizal
      fungi and mycorrhizal plants to elevated CO2 were significantly positive. The
      response ratio for ECM fungi was 1.34 (an increase of 34%) and for AM fungi 1.21
      (21%), indicating a significantly different response. The response ratio for ECM
      plants was 1.26, similar to that of AM plants (1.25). Fractional colonization
      proved to be an unsuitable fungal parameter. Evidence was found for the
      mycocentric view in ECM, but not in AM systems. Fungal identity and plant
      identity were important parameters that affected response ratios. The need for
      better descriptors of fungal and plant responses is emphasized.

PMID- 16101923
TI  - Arbuscular mycorrhizal fungi do not enhance nitrogen acquisition and growth of
      old-field perennials under low nitrogen supply in glasshouse culture.
AB  - Arbuscular mycorrhizal fungi (AMF) are known to promote plant growth when
      phosphorus is limiting, but the role of AMF in plant growth under nitrogen (N)
      limiting conditions is unclear. Here, we manipulated N (control vs inorganic and
      organic forms) and AMF species (control vs four AMF species) for five old-field
      perennials grown individually in a glasshouse under N-limiting conditions. We
      found that AMF were at best neutral and that some AMF species depressed growth
      for some plant species (significant plant-fungus interaction). Native plant
      species growth was strongly depressed by all but one AMF species; exotic plant
      species were less sensitive to AMF. We found no evidence of plant N preferences.
      Both natives and exotics were able to acquire more N with N addition, but only
      exotics grew more with added N. Our results suggest that AMF do not promote plant
      N acquisition at low N supply, and our results are consistent with other research
      showing that AMF can act as a parasitic carbon drain when phosphorus availability
      is relatively high.

PMID- 16101924
TI  - European and African maize cultivars differ in their physiological and molecular
      responses to mycorrhizal infection.
AB  - Physiological and molecular responses to phosphorus (P) supply and mycorrhizal
      infection by Glomus intraradices were compared in European (River) and African
      (H511) maize (Zea mays) cultivars to examine the extent to which these responses
      differed between plants developed for use in high- and low-nutrient-input
      agricultural systems. Biomass, photosynthetic rates, nutrient and carbohydrate
      contents, mycorrhizal colonization and nutrient-responsive phosphate transporter
      gene expression were measured in nonmycorrhizal and mycorrhizal plants grown at
      different inorganic phosphorus (P(i)) supply rates. Nonmycorrhizal River plants
      grew poorly at low P(i) but were highly responsive to mycorrhizal infection;
      there were large increases in biomass, tissue P content and the rate of
      photosynthesis and a decline in the expression of phosphate transporter genes.
      Nonmycorrhizal H511 plants grew better than River plants at low P(i), and had a
      higher root : shoot ratio. However, the responses of H511 plants to higher P(i)
      supplies and mycorrhizal infection were much more limited than those of River
      plants. The adaptations that allowed nonmycorrhizal H511 plants to perform well
      in low-P soils limited their ability to respond to higher nutrient supply rates
      and mycorrhizal infection. The European variety had not lost the ability to
      respond to mycorrhizas and may have traits useful for low-nutrient agriculture
      where mycorrhizal symbioses are established.

PMID- 16101925
TI  - Nodulated N2-fixing Casuarina cunninghamiana is the sink for net N transfer from
      non-N2-fixing Eucalyptus maculata via an ectomycorrhizal fungus Pisolithus sp.
      using 15NH4+ or 15NO3- supplied as ammonium nitrate.
AB  - To determine the effects of nitrogen source on rates of net N transfer between
      plants connected by a common mycorrhizal network, we measured transfer of N
      supplied as 15NH4 14NO3 or 14NH4 15NO3 in three Casuarina/Eucalyptus treatments
      interconnected by a Pisolithus sp. The treatments were nonnodulated
      nonmycorrhizal/nonmycorrhizal; nonnodulated mycorrhizal/mycorrhizal; and
      nodulated mycorrhizal/mycorrhizal. Mycorrhization was 67% in Eucalyptus and 36%
      in Casuarina. N2 fixation supplied 38% of the N in Casuarina. Biomass, N and 15N
      contents were lowest in nonmycorrhizal plants and greatest in plants in the
      nodulated/mycorrhizal treatment. Nitrogen transfer was enhanced by mycorrhization
      and by nodulation, and was greater when N was supplied as 15NH4+ than 15NO3-.
      Nitrogen transfer rates were lowest in the nonmycorrhizal treatment for either
      15N source, and greatest in the nodulated, mycorrhizal treatment. Transfer was
      greater to Casuarina than to Eucalyptus and where ammonium rather than nitrate
      was the N source. Irrespective of 15N source and of whether Casuarina or
      Eucalyptus was the N sink, net N transfer was low and was similar in both
      nonnodulated treatments. However, when Casuarina was the N sink in the nodulated,
      mycorrhizal treatment, net N transfer was much greater with 15NH4+ than with
      15NO3-. High N demand by Casuarina resulted in greater net N transfer from the
      less N-demanding Eucalyptus. Net transfer of N from a non-N2-fixing to an N2
      fixing plant may reflect the very high N demand of N2-fixing species.

PMID- 16101927
TI  - World Allergy Organization Congress--allergy in a changing world.

PMID- 16101928
TI  - Isocyanates, polyurethane and childhood asthma.
AB  - Isocyanates are the most prominent and well-studied cause of occupational asthma.
      Over the decades, airborne isocyanates have been regulated to extremely low
      levels in the workplace, some of the lowest for any organic compound. Yet the
      incidence of isocyanate-induced occupational asthma remains high and the role of
      dermal exposure in disease etiology is only slowly being recognized. Almost
      completely overlooked is the potential relationship between isocyanates in
      consumer products and increasing prevalence of asthma in the general population,
      especially children. The steady rise in asthma over the past decades points
      strongly to a potential role of environmental exposures in its development.
      Imbalances in the immune system favoring respiratory diseases have been linked to
      biological and chemical stressor exposures early in life. Evidence for the
      presence of isocyanates in many polyurethane-containing materials, especially
      polyurethane foams, is presented as a possible contributor to the increase in
      asthma. Polyurethane foam is ubiquitous in western societies and used in bedding,
      furniture, automobile seats, footwear, etc., and numerous medical materials.
      Theoretical, epidemiologic, experimental and clinical evidence of a role for
      isocyanates and polyurethanes in the genesis of non-occupational allergy and
      respiratory disease are reviewed. These data all point to the urgent need for
      additional research on the links between isocyanates, polyurethanes and the role
      of the skin in non-occupational asthma.

PMID- 16101929
TI  - Early rapid weight gain and current overweight in relation to asthma in
      adolescents born with very low birth weight.
AB  - Early catch-up growth and subsequent overweight are suggested to be associated
      with later cardiovascular diseases and later type II diabetes. However, the
      impact of early catch-up growth and childhood overweight on the development of
      asthma has been less studied, particularly in children born with very low birth
      weight (VLBW). A birth cohort of 74 VLBW children (birth weight < or = 1500 g)
      was followed from birth and investigated on asthma at 12 yr of age. Early rapid
      weight gain was in one way defined as an increase of weight > or =1 standard
      deviation score (SDS) at 6 months of corrected postnatal age. Current overweight
      was defined by body mass index (BMI) exceeding 21.2 and 21.7 kg/m(2),
      respectively, for boys and girls at 12 yr of age. Current asthma was diagnosed by
      a pediatrician, according to asthma ever in combination with a positive response
      to hypertonic saline bronchial provocation test and/or wheeze at physical
      examination at 12 yr old. Being overweight at 12 yr of age was associated with an
      increased risk for current asthma in the VLBW children [crude odds ratio (OR):
      5.5, 95% confidence interval (CI): 1.3-22.2]. After adjustment for early weight
      gain and neonatal risk, the OR of overweight increased nearly three times
      (adjusted OR: 15.3, 95% CI: 2.5-90.6). Early rapid weight gain seemed to be
      inversely associated with current asthma (adjusted OR: 0.49 for an increase of
      weight equal to 1 SDS, 95% CI: 0.23-1.02, p = 0.06). In addition, early rapid
      weight gain was inversely associated with the magnitude of bronchial
      responsiveness at 12 yr (coefficient -1.15, p < 0.01). There was a strong and
      positive association between overweight and asthma at 12 yr of age in the VLBW
      children. This strong association had been reduced by early rapid weight gain,
      possibly via the reduction of bronchial responsiveness.

PMID- 16101930
TI  - Hospitalization for RSV bronchiolitis before 12 months of age and subsequent
      asthma, atopy and wheeze: a longitudinal birth cohort study.
AB  - Several epidemiological studies have reported recurrent wheezing and asthma in
      children after respiratory syncytial virus (RSV) bronchiolitis in infancy. The
      relationship with allergic sensitization is less clear and recent evidence
      suggests an interaction between atopy and RSV infection in the development of
      asthma. Data from a large, population-based, birth-cohort (Avon Longitudinal
      Study of Parents and Children) were used to compare outcomes of children
      according to whether or not they had been admitted to hospital in the first 12
      months with RSV-proven bronchiolitis. Outcomes considered were 12-month
      prevalence of wheeze at two ages (between 30-42 and 69-81 months), cumulative
      prevalence of doctor-diagnosed asthma at 91 months and skin prick test defined
      atopy at 7 yr. Multivariable logistic regression models were used to calculate
      odds ratios for outcomes adjusted for potential confounders. A total of 150
      infants (1.1% of the cohort) were admitted to hospital within 12 months of birth
      with RSV bronchiolitis. The prevalence of wheezing was 28.1% in the RSV group and
      13.1% in controls at 30-42 months and 22.6% vs. 9.6% at 69-81 months. The
      cumulative prevalence of asthma was 38.4% in the RSV group and 20.1% in controls
      at 91 months. Atopy was found in 14.6% of the RSV group and in 20.7% of controls
      at 7 yr. RSV bronchiolitis was associated with subsequent wheezing between 30-42
      (Odds ratio [95% CI] 2.3 [1.3, 3.9]) and 69-81 months (OR 3.5 [1.8, 6.6]) and
      with the cumulative prevalence of asthma at 91 months (OR 2.5 [1.4, 4.3]) but not
      with atopy (OR 0.7 [0.2, 1.7]). In a population-based birth cohort, RSV
      bronchiolitis was associated with subsequent wheezing and asthma but not with the
      development of atopy by age 7 yr.

PMID- 16101931
TI  - A prospective study of wheezing in young children: the independent effects of
      cockroach exposure, breast-feeding and allergic sensitization.
AB  - The objective of this study was to evaluate risk factors for persistent wheezing
      in a group of 2-4-year-old children after an index-wheezing episode in infancy.
      Eighty infants who had been seen at the Emergency Department for an episode of
      acute wheezing were followed for 2 yr in this prospective study. Caregivers
      completed a questionnaire, and children underwent clinical evaluation and skin
      prick testing 2 yr following the index-wheezing episode. Detection of respiratory
      viruses and analysis of exposure to major indoor allergens were carried out at
      enrollment. Immunoglobin E antibodies were measured at the beginning of the study
      and at the end of follow-up, using the CAP system. Logistic regression analysis
      was performed to identify factors associated with persistent wheezing. Seventy
      three children (44 boys) completed the study. After 2 yr, 38 (52%) reported three
      or more wheezing episodes in the past 12 months (persistent wheezers).
      Independent risk factors for persistence of wheezing were allergic sensitization
      and exposure to cockroach allergen in the kitchen. Breast-feeding for at least 1
      month was a protective factor. A strong association between allergic
      sensitization and persistence of wheezing was found in a group of very young
      children living in a subtropical area.

PMID- 16101932
TI  - Sensitization to common indoor allergens and its association with allergic
      diseases in Thai female high-school students.
AB  - Allergic sensitization is generally agreed to be an important risk factor for
      allergic diseases. It has been demonstrated in most of the children attending
      allergy clinics in Thailand but has never been studied in Thai general
      populations. The objectives were (i) to describe the prevalence of sensitization
      to common indoor allergens in Thai female-high-school students and (ii) to
      evaluate the association of allergic sensitization to allergic diseases in these
      students. cross-sectional analytic study was designed. Seven hundred and six
      schoolgirls were enrolled during May-June 2002. Written ISAAC questionnaires were
      completed by the students and skin prick tests were performed in 344 (48.7%)
      students with a battery of seven common allergens including Dermatophagoides
      pteronyssinus, Dermatophagoides farinae, American cockroach, Cat, Cladosporium,
      Penicillium, and Aspergillus. Positive test was defined as a mean wheal diameter
      of at least 3 mm at the 15 min reading. The adjusted odds ratios (OR) and 95%
      confidence intervals (CI) were obtained from multiple regression analysis for the
      independent effect of sensitization to each allergen on allergic diseases. A
      total of 154 (44.8%) students had evidence of allergic sensitization on skin
      prick tests. The prevalence rates of sensitization to various groups of allergens
      were as follows; mites 43.0%, cockroach 12.8%, cat 4.1%, and molds 1.2%. The
      independent effect of allergic sensitization on allergic diseases was observed
      only in mite sensitization on nose problem (OR = 1.73, CI = 1.07-2.78 for nose
      problem ever and OR = 1.85, CI = 1.13-3.02 for nose problem in 12 months). The
      risk of nose problem was also increased with the number of positive reactions.
      CONCLUSION: We found that sensitization to the four common allergen groups were
      weakly associated with the presence of allergic diseases in Thai schoolgirls.
      This confirms the observation that the development of allergic diseases is not
      solely attributable to allergic sensitization.

PMID- 16101933
TI  - The prevalence, severity and seasonal variations of asthma, rhinitis and eczema
      in Taiwanese schoolchildren.
AB  - The prevalence of asthma is increasing in Taiwan but data remain limited. The aim
      of this study was to determine the prevalence, severity, demographic and seasonal
      variations of asthma, rhinitis, and eczema in Taiwan. Using a one-stage
      stratified cluster random sampling, first grade (aged 6-8) and eighth grade (aged
      13-15) students from Taoyuan, northern Taiwan, were invited to participate in
      this survey. The results showed a total of 6190 students, 3079 aged 6-8 and 3111
      aged 13-15, completed this survey. In general, children aged 6-8 had
      significantly higher prevalence rates of diagnosed asthma, rhinitis, and eczema
      than children aged 13-15 (12.2%, 29.8%, and 10.2% vs. 9.6%, 18.3%, and 4.7%,
      respectively). Similarly, children aged 6-8 had significantly higher proportions
      of allergic symptoms, except for exercise-induced wheezing (5.8% vs. 17.8%, p <
      0.0001). Among those with allergic disorders, children aged 6-8 presented a
      greater severity of wheezing attacks in the last 12 months. As regards gender,
      boys aged 6-8 had a significantly higher proportion of asthma or rhinitis
      symptoms than girls aged 6-8 but not in children aged 13-15. In children aged 6
      8, asthma and rhinitis peaked in winter, especially in December. However,
      children aged 13-15 had two peaks (winter and summer) for asthma or rhinitis.

PMID- 16101934
TI  - Urine leukotriene E and eosinophil cationic protein in nasopharyngeal aspiration
      from young wheezy children.
AB  - Respiratory syncytial virus (RSV) infection is a risk factor for the development
      of asthma. It is very hard to distinguish bronchiolitis with respiratory virus
      infection from allergic asthma at first wheezing attack in early childhood. To
      distinguish wheezing children with RSV bronchiolitis from asthmatic children, we
      measured leukotriene E(4)(LTE(4)) in urine and ECP in nasopharyngeal aspiration
      (NPA) at first day of admission with wheezing attack. Thirty-two non-atopic
      children younger than the age of 3 yr with RSV induced bronchiolitis, 35 atopic
      asthmatic children with/without respiratory viral infection, and 23 children who
      exhibited no evidence of atopy, asthma, or virus infections as controls were
      selected in this study. We measured urinary LTE(4) and ECP level in NPA from
      subjects. Urinary LTE(4) concentrations in children with asthma were
      significantly higher than urinary LTE(4) in bronchiolitis and in controls (240.8
      +/- 129.8 vs. 162.8 +/- 73.9 vs. 85.1 +/- 31.6 pg/ml). Children with RSV
      infection demonstrated higher urinary LTE(4) levels compared to children without
      RSV infection among asthmatic children. ECP in NPA was significantly correlated
      with urinary LTE(4) (r = 0.57, p < 0.01) in children entered this study who had
      detectable levels for both LTE(4) and ECP. In summary, Urinary LTE(4)
      concentrations may be suggested to useful mediators for differential diagnosis of
      wheezy diseases in early childhood. RSV infection also is associated with
      synergizing LT biosynthesis and this study demonstrated ECP in NPA was
      significantly correlated with urinary LTE(4) and may suggest that cysteinyl
      leukotriene initiate the production of ECP in early childhood, which could
      contribute to the development of wheeze.

PMID- 16101935
TI  - CTLA-4 expression in T cells of patients with atopic dermatitis.
AB  - Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152) is a surface molecule
      of activated T cells with sequence homologous to CD28, and may act as a negative
      regulator of T-cell activation. In murine animal models, cross-linkage of CTLA-4
      molecules on the cell surface results in decreased T-cell proliferation,
      accompanied by increased interleukin (IL)-2 production and apoptosis. To clarify
      the activation of peripheral blood T cells, we studied the CTLA-4 expression in
      32 patients with atopic dermatitis who visited our institution, and 19 normal
      children who visited for pre-operative laboratory examination were used as normal
      controls. Whole blood was obtained from all subjects and stained with anti-CD3,
      anti-CD4, anti-CD8 monoclonal antibodies (mAb). After erythrocyte lysis with
      lysing solution, the cells were stained with anti-CTLA-4 mAb, and stained cells
      were analysed by fluorescence-activated cell sorter (FACScan) flow cytometer.
      Intracellular expression of CTLA-4 was significantly upregulated in peripheral
      blood CD3+ T cells (36.8%), CD4+ T cells (21.7%) and CD8+ T cells (18.7%) of
      patients with atopic dermatitis, compared with normal control (18.3%, 9.7%, 9.8%;
      respectively). Furthermore, CTLA-4-positive CD3+ T cells in patients with severe
      atopic dermatitis were significantly higher compared with milder group (42.8% vs.
      32.2%). However, no significant difference was obtained in CD4+ and CD8+ T cells.
      Mean percentage of T cells expressing CTLA-4 in patients with atopic dermatitis
      was higher than the control group. These observations suggest the possibility
      that the disease activity can be correlated with the CTLA-4 level.

PMID- 16101936
TI  - Chronic urticaria and associated coeliac disease in children: a case-control
      study.
AB  - Celiac disease (CD) and chronic urticaria (CU) are both sustained by immune
      mechanisms, but there are so far few data on their clinical association. We
      performed a case-control study to determine the occurrence of CD in urticaria and
      matched control children, and to assess the clinical relevance of this
      association. Children and adolescents were diagnosed to have severe chronic
      idiopathic urticaria in the presence of hives for more than 6 wk poorly or not
      responsive to oral antihistamines. Other known causes of urticaria had to be
      excluded. A matched control group without urticaria was enrolled. In both groups,
      the presence of CD was searched by assaying antitransglutaminase and
      antiedomysial antibodies, and confirmed with endoscopic intestinal biopsy.
      Results. CD was diagnosed and confirmed in 4/79 (5.0%) of children with CU and in
      17/2545 (0.67%) of the controls (p = 0.0003). In the four children with urticaria
      and CD the gluten free diet (GFD) lead to complete remission of urticaria within
      5-10 wk, whereas the disappearance of serological markers occurred in longer
      times (5-9 months). CONCLUSIONS: The presence of CD in children with CU was
      significantly more frequent than in controls. GFD resulted in urticaria
      remission. CD may be regarded in such subjects as a cause of CU.

PMID- 16101937
TI  - The efficacy and safety of heat-killed Lactobacillus paracasei for treatment of
      perennial allergic rhinitis induced by house-dust mite.
AB  - Live Lactobacillus paracasi 33 (LP33) may effectively improve the quality of life
      for patients with perennial allergic rhinitis. It has been demonstrated that heat
      killed lactic acid bacteria (LAB) suppress specific immunoglobulin E synthesis
      and stimulate interleukin-12 production in animals. The aim of this study was,
      therefore, to evaluate the efficacy of heat-killed LP33 in the treatment of
      allergic rhinitis induced by house-dust-mite in human subjects. A total of 90
      patients were enrolled in a randomized, double blind, placebo-controlled trial
      and assigned to three treatment groups. Patients in groups A and B received two
      capsules per day of live or heat-killed LAB (5 x 10(9) colony-forming
      units/capsule), respectively, over a period of 30 days while those in Group C
      received placebo capsules. A modified questionnaire on pediatric
      rhinoconjunctivitis-related quality of life was administered to all subjects or
      their parents during each clinical visit. The overall quality of life score
      decreased for groups A and B, as compared with the placebo group, in terms of
      both frequency (9.47 +/- 2.89, 6.30 +/- 2.19, vs. -3.47 +/- 1.53, respectively; p
      < 0.0001) and level of bother (5.91 +/- 3.21, 6.04 +/- 2.44, vs. -2.80 +/- 1.64,
      respectively; p = 0.004) after the 30-day treatment. The efficacy of the heat
      killed LP33 was not inferior to the live variant. No obvious side effects were
      reported for either active treatment group during the study period. Our results
      suggest that heat-killed LP33 can effectively improve the overall quality of life
      for patients with allergic rhinitis, and that it may be efficacious as an
      alternative treatment.

PMID- 16101938
TI  - Increased IFN-gamma secretion from duodenal biopsy samples in delayed-type cow's
      milk allergy.
AB  - A delayed and local gastrointestinal hypersensitivity to cow's milk (CM) protein
      is difficult to diagnose and there are limited data on this disorder. The aim of
      this study was to investigate local intestinal cytokine secretion in the upper
      small intestine in children with delayed-type cow's milk allergy (CMA). Duodenal
      biopsy samples from 31 children with delayed CMA, 14 with celiac disease (CD),
      and 14 healthy controls were studied for the spontaneous release of IFN-gamma,
      TNF-alpha, IL-2, IL-4, IL-5, and IL-10, measured by cytometric bead array, and of
      TGF-beta and IL-6 measured by ELISA. The children with delayed CMA secreted more
      IFN-gamma than the controls (p = 0.006) and the children with CD (p = 0.006). The
      children with CD secreted more IL-6 compared to the controls (p = 0.008) and the
      children with delayed CMA (p = 0.002). The children with delayed CMA who had
      continuously been exposed to CM secreted less TGF-beta than the children with
      delayed CMA who avoided CM (p = 0.050), and showed a tendency towards lower
      secretion compared to the controls (p = 0.078). Secretions of TNF-alpha, IL-2, IL
      4, IL-5, and IL-10 were low in general; however, the children with delayed CMA
      who did not avoid CM secreted more IL-4 and IL-10 than the controls (p = 0.016,
      0.059). In conclusion, the children with delayed CMA showed up-regulation of IFN
      gamma. Interestingly, TGF-beta secretion was up-regulated in those children with
      delayed CMA who avoided CM suggesting recovery of regulation mechanisms.

PMID- 16101939
TI  - Infantile hepatic dysfunction improved by elimination of cows' milk formulas.
AB  - We present three infants who showed hypertransaminasemia without extrahepatic
      symptoms, which improved by eliminating cows' milk formulas. The levels of milk
      protein-specific lymphocyte proliferation were elevated in all three patients.
      These cases indicate the importance of food allergy in the diagnosis of infantile
      hepatic dysfunction.

PMID- 16101940
TI  - Parental smoking and allergic sensitization in offspring defined by skin prick
      testing.
AB  - Investigations of parental smoking during childhood and allergic sensitization
      have produced contradictory results, but this may be because of variations in the
      definition of allergy and other influences. We investigated associations of
      parental smoking with an objective measure of allergy, skin prick testing (SPT),
      and considered associations with maternal and paternal smoking, independently of
      each other. A stratified random sample, aged 22-74 yr, of 720 Swedish FinEsS
      study members were skin prick tested for 15 allergens. Subjects with at least one
      positive SPT were defined as atopic. Data on childhood exposures, including
      parental smoking, were collected by structured interview. Logistic regression
      used atopy as the dependent variable. After adjustment, paternal smoking was
      statistically significantly associated with an increased risk and maternal
      smoking a non-statistically significant decreased risk in offspring, with odds
      ratios (and 95% confidence intervals) of 1.48 (1.04-2.10) and 0.73 (0.48-1.12),
      respectively. Analysis of families with a non-smoking mother produced an odds
      ratio for paternal smoking of 1.61 (1.09-2.37). The negative association between
      maternal smoking and atopy may not operate through passive smoke exposure and
      could conceal a significant increased risk associated with passive exposure to
      tobacco smoke in childhood.

PMID- 16101941
TI  - Anaphylactic reaction and unrelated, subsequent, known side effects during
      therapy with thiethylperazine.
AB  - We report the first case presenting with successive anaphylactic reaction and
      extra-pyramidal syndrome after treatment with thiethylperazine maleate
      (thiethylperazine). Both reactions were caused due to this anti-emetic drug, but
      an additive effect of clemastine fumarate, prescribed to treat the anaphylactic
      reaction, is suggested by the sequence of events. We discuss the importance of
      knowing the pharmacological similitudes of common prescribed drugs in order to
      avoid the occurrence of side effects.

PMID- 16101942
TI  - CT genotype of promotor polymorphism C159T in the CD14 gene is associated with
      lower prevalence of atopic dermatitis and lower IL-13 production.

PMID- 16101943
TI  - Myopia and associated pathological complications.
AB  - Besides the direct economic and social burden of myopia, associated ocular
      complications may lead to substantial visual loss. In several population and
      clinic-based cohorts, case-control and cross-sectional studies, higher risks of
      posterior subcapsular cataract, cortical and nuclear cataract in myopic patients
      were reported. Patients with high myopia (spherical equivalent at least -6.0 D)
      are more susceptible to ocular abnormalities. The prevalent risks of glaucoma
      were higher in myopic adults, and risks of chorioretinal abnormalities such as
      retinal detachment, chorioretinal atrophy and lacquer cracks increased with
      severity of myopia and greater axial length. Myopic adults were more likely to
      have tilted, rotated, and larger discs as well as other optic disc abnormalities.
      Often, these studies support possible associations between myopia and specific
      ocular complications, but we cannot infer causality because of limitations in
      study methodology. The detection and treatment of possible pathological ocular
      complications is essential in the management of high myopia. The ocular risks
      associated with myopia should not be underestimated and there is a public health
      need to prevent the onset or progression of myopia.

PMID- 16101944
TI  - Silent substitution S-cone electroretinogram in subjects with diabetes mellitus.
AB  - A defect in the blue sensitive mechanism has been reported in certain ocular and
      systemic diseases. For example, tritanopic colour vision defects and changes to
      the S-cone electroretinogram (ERG) have been demonstrated in glaucoma and
      diabetes mellitus. Electrophysiological methods of eliciting the S-cone ERG,
      however, often result in considerable L- and M-cone intrusion. We report the
      findings of a study employing the silent substitution S-cone ERG technique, which
      is thought to represent an almost pure S-cone signal, and the L'Anthony
      desaturated D15 colour vision test in subjects with Type 1 or 2 diabetes mellitus
      with no or minimal background retinopathy. The results of this study show a
      significantly increased S-cone ERG b-wave implicit time and significantly worse
      colour vision in those with background retinopathy compared with those with no
      diabetic retinopathy. This suggests that S-cone pathway dysfunction may be
      responsible for the deterioration in colour vision found in diabetes mellitus.

PMID- 16101945
TI  - The effect of strabismus on a young child's selection of a playmate.
AB  - PURPOSE: This study investigated the effect of strabismus on a child's playmate
      selection. METHODS: Photographs of orthotropic children aged 3-6 years were
      altered to simulate various magnitudes of strabismus. The pictures were arranged
      in pairs, one orthotropic child and one with strabismus. One hundred children
      aged 3-8 years viewed the photographs and were asked to select a playmate from
      each pair. RESULTS: Chi-squared analysis found 23 children showed evidence that
      strabismus influenced their choices (p < 0.07). Of these 23, 12 preferred
      playmates with strabismus and 11 preferred orthotropic playmates. Chi-squared
      analysis of all subjects combined found decisions were not based on the magnitude
      or direction of strabismus. CONCLUSIONS: As only 11% of the children consistently
      selected against playmates with strabismus, and about the same percentage
      preferred playmates with strabismus (12%), the presence of strabismus does not
      appear to be a significant factor in peer acceptance in this age group.

PMID- 16101946
TI  - Comparing glaucomatous optic neuropathy in primary open angle and chronic primary
      angle closure glaucoma eyes by optical coherence tomography.
AB  - PURPOSE: To comparatively evaluate the optic nerve head (ONH) using Optical
      Coherence Tomography (OCT) in normal subjects, primary open angle glaucoma (POAG)
      and chronic primary angle closure glaucoma (CPACG) patients. METHODS: A total of
      138 normal eyes (138 subjects) and 139 glaucomatous eyes (139 patients), were
      evaluated in this cross-sectional observational study. The ONH was imaged on OCT
      using the optic disc scan. Disc area, cup area, rim area, vertical integrated rim
      area (VIRA), rim volume (horizontal integrated rim volume), average cup/disc
      ratio, horizontal and vertical cup/disc ratios, and cup volume were evaluated.
      Additionally, cup depth and slope of the temporal ONH were also measured. These
      ONH parameters were compared between normal subjects and eyes with early POAG and
      CPACG. Correlation of mean deviation and corrected pattern standard deviation on
      full threshold 30-2 perimetry, with measured ONH parameters was carried out
      amongst the two groups. RESULTS: There was a significant difference in disc area
      (2.38 +/- 0.5, 2.77 +/- 0.4, 2.62 +/- 0.4 mm(2), p < 0.01), cup area (0.88 +/-
      0.6, 1.99 +/- 0.7, 1.60 +/- 0.7 mm(2), p < 0.01), rim area (1.48 +/- 0.4, 0.86 +/
      0.4, 0.96 +/- 0.4 mm(2), p < 0.01), VIRA (1.64 +/- 0.3, 1.23 +/- 0.3, 1.22 +/-
      0.4 mm(2), p < 0.01), rim volume (0.34 +/- 0.2, 0.1 +/- 0.1, 0.15 +/- 0.1 mm(3),
      p < 0.01) and cup/disc ratio (0.36 +/- 0.2, 0.69 +/- 0.1, 0.63 +/- 0.2, p < 0.01)
      in normal vs POAG vs CPACG eyes respectively. A comparison of ONH parameters
      between early POAG and early CPACG showed a significant difference in the disc
      area (2.85 +/- 0.3, 2.57 +/- 0.4 mm(2), p = 0.03), cup area (2 +/- 0.5, 1.34 +/-
      0.5 mm(2), p < 0.01), rim area (0.96 +/- 0.4, 1.21 +/- 0.5 mm(2), p = 0.009), rim
      volume (0.12 +/- 0.1, 0.18 +/- 0.1 mm(3), p < 0.01) and cup/disc ratio (0.67 +/-
      0.1, 0.53 +/- 0.2, p < 0.01). The parameters with the highest area under the
      receiver operator characteristic (AROC) curves for differentiating normal and
      early POAG eyes were rim volume, 0.89, VIRA, 0.84, and rim area, 0.76. The AROC
      values (normal vs early CPACG eyes) were 0.75 for rim volume, 0.72 for VIRA, and
      0.66 for rim area. CONCLUSION: OCT may serve as a useful diagnostic modality in
      distinguishing a normal optic disc from a glaucomatous one, even in the early
      stages of glaucoma. Rim volume, VIRA and rim area can be used to differentiate
      normal from early glaucoma (both early POAG and CPACG), and most efficiently
      early POAG eyes. CPACG eyes have smaller discs, a smaller cup, smaller cup/disc
      ratio, and a larger rim area when compared with eyes with POAG.

PMID- 16101947
TI  - The Proview Eye Pressure Monitor: influence of clinical factors on accuracy and
      agreement with the Goldmann tonometer.
AB  - PURPOSE: To investigate (i) the effect of probe position on the lid when using
      the Proview Eye Pressure Monitor (Proview) and (ii) the accuracy of the Proview
      and its agreement with the Goldmann applanation tonometer (GAT) in a normal
      population. METHODS: Intraocular pressure (IOP) measurements were performed on
      107 control subjects (mean 25 years) using the Proview and the GAT. The Proview
      probe was applied to two locations on the eyelid (superior nasal and superior
      temporal). The IOPs measured with both instruments were compared. RESULTS: A
      total of 4.6% of young normal eyes could not perceive the phosphene. The mean
      Proview reading using the recommended nasal lid position was significantly higher
      (+2.5 mmHg) than that measured using the GAT. The position of the probe
      application was significant, with temporal lid application giving statistically
      significantly higher IOP readings than the recommended nasal lid application. The
      repeatability of Proview measurements was lower than the GAT (coefficients of
      repeatability of GAT and Proview nasal were 0.96 and 4.21 mmHg respectively). The
      limit of agreement between the GAT and the Proview nasal was low at +/-7.95 mmHg.
      CONCLUSION: This study shows that the position of probe application can influence
      the measurements taken using the Proview. Application of the probe to the nasal
      superior lid (as recommended) gives the more repeatable and accurate results.
      Overall however the data indicate that the Proview is neither sufficiently
      accurate nor repeatable to be used in the detection and management of glaucoma.
      More work is needed in developing this interesting product.

PMID- 16101948
TI  - Evaluation of the pressure phosphene tonometer as a self-tonometer.
AB  - PURPOSE: Different from conventional tonometers, the pressure phosphene tonometer
      (FPT) measures intraocular pressure (IOP) through the upper eyelid without
      corneal applanation. We evaluated the usefulness of the FPT as a self-tonometer
      by comparing FPT IOP readings with those obtained with the Goldmann applanation
      tonometer (GAT). We also evaluated the influence of central corneal thickness
      (CCT) on IOP measurements obtained with the two different devices. METHODS: We
      confirmed the repeatability of FPT measurements in a preliminary study. The main
      investigation formed part of a prospective clinical trial, in which IOP was
      measured in 101 eyes of 101 participants (55 normal and 46 glaucomatous eyes)
      using GAT and FPT. FPT measurements were self-acquired by each participant. CCT
      was measured with an ultrasonic pachymeter. The agreement between FPT and GAT
      measurements was evaluated by the method of Bland and Altman. Using individual
      IOP and CCT values, we determined the correlation coefficients and performed
      regression analysis. RESULTS: FPT met the British Standard criteria for
      reproducibility. Among 101 participants, seven patients with glaucoma were unable
      to detect the pressure phosphene and to measure IOP using the FPT. By the
      statistical method of Bland and Altman there was a significant difference between
      FPT readings self-measured by the remaining 94 participants and GAT readings
      obtained by an ophthalmologist. There was no correlation between FPT and CCT
      readings in 65 participants with no prior history of anti-glaucoma medications or
      glaucoma surgery. CONCLUSIONS: Self-tonometer FPT readings differed from GAT
      readings. However, we suggest that the FPT may be a clinically acceptable device
      because it enables patients to self-measure their IOP easily and safely. As FPT
      readings are not affected by CCT, this tonometer may be of clinical and practical
      value for the at-will measurement of IOP in patients with corneal changes.

PMID- 16101949
TI  - Three portable tonometers, the TGDc-01, the ICARE and the Tonopen XL, compared
      with each other and with Goldmann applanation tonometry*.
AB  - Three portable tonometers, the TGDc-01, the ICARE and the Tonopen XL, were
      compared with each other and to Goldmann applanation tonometry in a large group
      of healthy subjects and patients with ocular hypertension or glaucoma (n = 103).
      Measurements performed with the ICARE and the Tonopen XL were in good agreement
      with that of the Goldmann tonometer. Intraocular pressure (IOP) values measured
      with the TGDc-01 were significantly lower and showed more variability. The 95%
      limits of agreement (portable tonometer - Goldmann) were -17 to +10 mmHg for the
      TGDc-01, -6 to +7 mmHg for the ICARE and -6 to +8 mmHg for the Tonopen. Corneal
      thickness could not explain the differences between an IOP measured with the
      portable tonometers and an IOP measured with the Goldmann tonometer. Patient
      comfort was slightly higher for ICARE when compared with the Tonopen.

PMID- 16101950
TI  - Comparison of the ICare rebound tonometer with the Goldmann tonometer in a normal
      population.
AB  - The aim of this study was to evaluate the accuracy of measurement of intraocular
      pressure (IOP) using a new induction/impact rebound tonometer (ICare) in
      comparison with the Goldmann applanation tonometer (AT). The left eyes of 46
      university students were assessed with the two tonometers, with induction
      tonometry being performed first. The ICare was handled by an optometrist and the
      Goldmann tonometer by an ophthalmologist. In this study, statistically
      significant differences were found when comparing the ICare rebound tonometer
      with applanation tonometry (AT) (p < 0.05). The mean difference between the two
      tonometers was 1.34 +/- 2.03 mmHg (mean +/- S.D.) and the 95% limits of agreement
      were +/-3.98 mmHg. A frequency distribution of the differences demonstrated that
      in more than 80% of cases the IOP readings differed by <3 mmHg between the ICare
      and the AT. In the present population the ICare overestimates the IOP value by
      1.34 mmHg on average when compared with Goldmann tonometer. Nevertheless, the
      ICare tonometer may be helpful as a screening tool when Goldmann applanation
      tonometry is not applicable or not recommended, as it is able to estimate IOP
      within a range of +/-3.00 mmHg in more than 80% of the population.

PMID- 16101951
TI  - Should Orbscan pachometry be performed before or after Goldmann applanation
      tonometry?
AB  - PURPOSE: To compare the Orbscan central corneal thickness (CCT) values before and
      after intraocular pressure (IOP) measurement with Goldmann applanation tonometry
      in young normal adults. MATERIALS AND METHODS: Fifty-three eyes of 53 subjects
      who were free from any ocular problems were studied. The measurements included
      optical pachometry by the Orbscan II system, followed by Goldmann applanation
      tonometry, and finally Orbscan optical pachometry again. Standard Goldmann
      technique was adopted with the application of one drop of 0.4% benoxinate and
      fluorescein sodium prior to the measurement. The same operator was involved in
      the Orbscan pachometry before and after Goldmann tonometry. Another investigator
      was responsible for Goldmann tonometry. Three readings were obtained in each
      case, and the means were used for analysis. RESULTS: The mean IOP of the sample
      was 14.6 +/- 2.6 mmHg. There was no significant difference (paired t-test: p =
      0.50) in the mean CCT values before and after the Goldmann tonometry (551 +/- 32
      and 552 +/- 35 microm respectively). CONCLUSION: Standard Goldmann applanation
      tonometry does not affect the Orbscan CCT values. Measurement of CCT for the
      adjustment of true IOP can be carried out either before or after Goldmann
      tonometry.

PMID- 16101952
TI  - An enhancement to the Maddox Wing test for the reliable measurement of horizontal
      heterophoria.
AB  - PURPOSE: To attempt to improve the reliability of the Maddox Wing (MW) test for
      the measurement of horizontal heterophoria at near. METHODS: Horizontal
      heterophoria measurements at 30 cm using the MW instrument were made on a group
      of 58 normally-sighted binocular young adult subjects. The procedures were
      repeated at each of five weekly visits. The standard tangent scale card provided
      by the instrument's manufacturer was used as the control condition vs four
      alternative cards designed to enhance accommodative stimulation and improve
      operational reliability. RESULTS: A statistically-similar mean near phoria value
      was recorded using each of the five cards. However one of the alternative card
      designs produced a small but statistically significantly less variable result
      than the others: this design featured a much smaller typeface (4pt) than that
      used for the digits on the standard card, and the horizontal row of numbers was
      flanked by two periods of a low spatial frequency (< 2 c deg(-1)) square wave
      grating. CONCLUSIONS: It is suggested that for improved reliability of near
      phoria measurement when using the MW instrument a more appropriately detailed
      design of tangent card would promote enhanced accommodation, an operational
      consideration likely to be especially relevant when examining children.

PMID- 16101953
TI  - Recovery of the water content of hydrogel contact lenses after use.
AB  - The aim of the present study is to determine the amount and time of water-content
      recovery of ionic contact lenses (Surevue and Acuvue) and non-ionic contact
      lenses (Soflens 38, Soflens 66 and Optima 38) when submerged in maintenance
      solution for 9 h. Using a hand-held refractometer, we measured the water content
      of the lenses upon removal from the eye, and after 15, 30, 45 min, 1, 2 and 9 h
      in soaking solution. Both ionic lenses presented pre-wear water content of 58%,
      while two of the non-ionic ones (Soflens 38 and Optima 38) registered 38.6% and
      the third (Soflens 66) had 66%. We found a significant increase (p < 0.05) in
      water content after submersion in the Opti-Free solution for all the time periods
      studied and for all lenses. The water-content recovery was faster in the non
      ionic lenses (Soflens 38, Soflens 66 and Optima 38) than in the ionic ones
      (Surevue and Acuvue), especially at 15 min. After 9 h in the soaking solution,
      the Surevue Acuvue, Soflens 38, Soflens 66 and Optima 38 lenses reached water
      content recovery values of 99.7%, 99.6%, 99.8%, 99.8% and 99.6%, respectively,
      without significant differences (p > 0.05) between ionic and non-ionic lenses,
      although the non-ionic lenses reached slightly higher water-content values at all
      the times studied. These results indicate that when the refractometer technique
      is used to measure water content, the lens types used in this study regain their
      initial water-content values after 9 h in soaking solution. These data indicate
      the time needed for hydrogel contact lenses to reach their maximum water content
      after removal from the eye and submersion in maintenance solution. By ensuring
      maximum water content and minimum reduction of oxygen for the cornea, the
      specialist can help avoid clinical signs and symptoms related to low water
      content in the lenses.

PMID- 16101955
TI  - Difficulty in obtaining feedback of refractive results following cataract
      surgery.

PMID- 16101956
TI  - Comments on 'The average eye' by W.F. Harris, Ophthal. Physiol. Opt. 2004 24: 580
      585.

PMID- 16101960
TI  - Immunization by Arg-gingipain A DNA vaccine protects mice against an invasive
      Porphyromonas gingivalis infection through regulation of interferon-gamma
      production.
AB  - We previously demonstrated that a Porphyromonas gingivalis rgpA DNA vaccine
      induced protective immune responses against P. gingivalis infection in mice. In
      the present study, reduction in lethality against infection by lethal doses of P.
      gingivalis was observed in the rgpA DNA vaccine-immunized mice. Cytokine levels
      in the mouse model with nonlethal doses of infection by P. gingivalis were
      evaluated to analyze the mechanism of protection by immunization with the rgpA
      DNA vaccine. After nonlethal challenge with invasive P. gingivalis W50,
      production of interleukin (IL)-2, IL-4, IL-5 and IL-12 was elevated; however,
      interferon (IFN)-gamma was lower in the serum of the DNA vaccine-immunized mice
      than in the serum of nonimmunized mice. The regulation of IFN-gamma production
      elicited by immunization with the rgpA DNA vaccine may play a significant role in
      protection against P. gingivalis infection in mice.

PMID- 16101961
TI  - Differentiation of mutans streptococci by intact cell matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - It is difficult to distinguish mutans streptococci on the species level, and even
      more so on the subspecies level. Intact cell matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) (ICM) was
      applied to reference strains of five of the species of the mutans group
      (Streptococcus criceti, Streptococcus downei, Streptococcus mutans, Streptococcus
      ratti, Streptococcus sobrinus), nonmutans streptococci (Streptococcus oralis,
      Streptococcus mitis, Streptococcus salivarius, and Streptococcus sanguinis), and
      177 mutans streptococci isolated from saliva of 10 children. From the analysis of
      the reference strains, readily distinguishable ICM mass spectra were obtained for
      the different species. Based on multivariate statistical analysis, a correct and
      unambiguous assignment was made of the spectra of 159 isolated mutans
      streptococci to S. mutans and 16 isolates to S. sobrinus. Two isolates were
      sorted out and were identified by sequencing of their 16S rRNA genes as
      Streptococcus anginosus. In addition, ICM indicated a misclassification for some
      reference strains (AHT, V 100 and E 49) and re-classified AHT and E 49 as S.
      ratti and V 100 as S. sobrinus. This was confirmed by 16S rDNA sequencing. Based
      on a statistical similarity analysis of the spectra of reference strains and a
      quantitative assessment of the reproducibility of ICM, the isolates identified as
      either S. mutans or S. sobrinus were phenotyped on the subspecies level. In the
      population of the clinical isolates, 14 unambiguously different S. mutans and
      three different S. sobrinus phenotypes were detected. ICM proved to be a powerful
      tool for a differentiation of mutans streptococci down to the subspecies level.

PMID- 16101962
TI  - Influence of genetic background on transformation and expression of Green
      Fluorescent Protein in Actinobacillus actinomycetemcomitans.
AB  - BACKGROUND/AIMS: The development of an electro-transformation system and the
      construction of shuttle plasmids for Actinobacillus actinomycetemcomitans have
      enhanced the molecular analysis of virulence factors. However, inefficient
      transformation is frequently encountered. This study investigated the efficiency
      of electro-transformation and expression of Green Fluorescent Protein (GFP) in 12
      different A. actinomycetemcomitans strains. The influence of the plasmid vector,
      serotype, and phenotype were the major factors taken into consideration. MATERIAL
      AND METHODS: Twelve serotyped A. actinomycetemcomitans strains were independently
      electro-transformed with two different Escherichia coli-A. actinomycetemcomitans
      shuttle plasmids (pVT1303 and pVT1304), both containing an identical ltx-GFPmut2
      gene construct but a different backbone (pDMG4 and pPK1, respectively). The
      transformation efficiency, transformation frequency, and electro-transformation
      survival rate were determined by culture techniques. GFP expression was observed
      at the colony level by fluorescence microscopy. RESULTS: All strains could be
      transformed with both plasmids. However, major differences were observed for the
      transformation efficiency, transformation frequency, and electro-transformation
      survival rate between strains. The data demonstrated that plasmid vector,
      serotype, and phenotype are key players for obtaining a successful
      transformation. An inverted relationship between the electro-transformation
      survival rate and tranformation frequency was also observed. GFP expression was
      also influenced by phenotype, serotype and plasmid vector. CONCLUSIONS: The
      serotype of A. actinomycetemcomitans has an important influence on its survival
      after electro-transformation and on transformation frequency. The expression of
      GFP is strain and plasmid vector dependent.

PMID- 16101963
TI  - T-cell independent production of salivary secretory IgA after hematopoietic stem
      cell transplantation in children.
AB  - This study examined the recovery of secretory IgA (S-IgA) in saliva after
      hematopoietic stem cell transplantation (HSCT) in 35 children and young people
      between the ages of 3 and 27 years (mean=13.6), and compared this recovery with
      that of serum immunologic constituents. Reference values for human salivary S-IgA
      in saliva were obtained from 77 healthy control subjects between the ages of 7
      and 25 years (mean=11.4). In the 35 patients, a nadir of secretory IgA
      concentrations in saliva (S-IgA) was observed between the 3rd and the 4th month,
      and a return to normal values 1 year after HSCT. Serum IgA concentrations reached
      their nadir in the 6th month, and normalized in the 18 months after HSCT. The
      recovery of T-helper cells (CD4+/3+) was also delayed to beyond 18 months. We
      found a significant correlation between the reconstitution pattern of S-IgA and
      that of T-helper lymphocytes, but no correlation was found between the post
      transplant evolutions of S-IgA and serum IgA, or between S-IgA and T-helper
      cells. The recovery of S-IgA was more rapid than that of serum IgA and appeared
      to be T-helper cell independent.

PMID- 16101964
TI  - Detection of bacteria in endodontic samples by polymerase chain reaction assays
      and association with defined clinical signs in Italian patients.
AB  - BACKGROUND/AIMS: The presence of selected bacteria (Enterococcus faecalis,
      Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythensis,
      Treponema denticola) in infected root canals was studied using polymerase chain
      reaction (PCR) assays, and the association of bacteria with clinical signs of
      endodontic disease was assessed. The null hypothesis, that no difference could be
      observed between clinical signs of apical periodontitis and a specific bacterial
      strain, was tested. METHODS: Microbial samples were obtained from 62 teeth in 54
      patients with endodontic disease. For each tooth, clinical data including patient
      symptoms were collected. Teeth were categorized by diagnosis as having acute
      apical periodontitis (AAP, teeth with clinical symptoms but no periapical
      radiolucency, n=22), chronic apical periodontitis (CAP, teeth with radiolucency
      but no clinical symptoms, n=15) or exacerbated apical periodontitis (EAP, teeth
      with symptoms and radiolucency, n=25). Seventy-one percent of cases were primary
      endodontic infections, and 29% were recurrent ('secondary') endodontic infections
      (failing cases). PCR assays were used to detect the presence of the selected
      bacteria. RESULTS: T. denticola and E. faecalis were each detected in 15 of 62
      samples (24%), P. gingivalis in 8 samples (13%), P. intermedia in 5 samples (8%),
      and T. forsythensis in 4 samples (7%). T. denticola was detected in 56% of teeth
      with EAP. E. faecalis was found in 60% of teeth with CAP and in 72% of teeth with
      secondary infection. Statistical analysis demonstrated an association of CAP and
      secondary endodontic infection with the presence of E. faecalis. (P<0.01). EAP
      was associated with the presence of T. denticola (P<0.01). CONCLUSION: T.
      denticola was associated with symptomatic endodontic disease in the presence of
      apical bone resorption. E. faecalis was associated with treatment failures. We
      suggest that these species may play critical roles in endodontic pathology.

PMID- 16101965
TI  - Cross-reactivity of GroEL antibodies with human heat shock protein 60 and
      quantification of pathogens in atherosclerosis.
AB  - BACKGROUND/AIMS: Chronic infections such as those caused by Chlamydia pneumoniae
      and periodontopathic bacteria such as Porphyromonas gingivalis have been
      associated with atherosclerosis, possibly due to cross-reactivity of the immune
      response to bacterial GroEL with human heat shock protein (hHSP) 60. METHODS: We
      examined the cross-reactivity of anti-GroEL and anti-P. gingivalis antibodies
      with hHSP60 in atherosclerosis patients and quantified a panel of six pathogens
      in atheromas. RESULTS: After absorption of plasma samples with hHSP60, there were
      variable reductions in the levels of anti-GroEL and anti-P. gingivalis
      antibodies, suggesting that these antibodies cross-reacted with hHSP60. All of
      the artery specimens were positive for P. gingivalis. Fusobacterium nucleatum,
      Tannerella forsythia, C. pneumoniae, Helicobacter pylori, and Haemophilus
      influenzae were found in 84%, 48%, 28%, 4%, and 4% of arteries, respectively. The
      prevalence of the three periodontopathic microorganisms, P. gingivalis, F.
      nucleatum and T. forsythia, was significantly higher than that of the remaining
      three microorganisms. CONCLUSIONS: These results support the hypothesis that in
      some patients, cross-reactivity of the immune response to bacterial HSPs
      including those of periodontal pathogens, with arterial endothelial cells
      expressing hHSP60 may be a possible mechanism for the association between
      atherosclerosis and periodontal infection.

PMID- 16101966
TI  - Molecular analysis of the genes involved in the biosynthesis of serotype specific
      polysaccharide in the novel serotype k strains of Streptococcus mutans.
AB  - We previously reported the new serotype k of Streptococcus mutans, which,
      compared to serotypes c, e, and f, features a drastic reduction in the length of
      the glucose side chain linked to the rhamnose backbone of the serotype specific
      polysaccharide. The 5' region of the rgpF gene of serotype k strains contains a
      distinctive nucleotide sequence, which suggests that an alteration of the rgpF
      gene in serotype k strains may explain the shortened glucose side chain. However,
      in the present study, expression of the rgpF gene of MT8148 (serotype c) in
      serotype k isolates was not found to lead to serotype conversion. Furthermore,
      mRNA expression of rgpE, known to be associated with glucose side chain
      formation, was not detected in any of the tested serotype k isolates with an RT
      PCR method. The nucleotide alignment of all genes known to be involved in the
      biosynthesis of serotype specific polysaccharide in serotype k strains was shown
      to be quite similar to that of serotype c strains, as compared to serotype e and
      f strains, especially in the region downstream of rgpF. Our results indicate that
      the common characteristics of serotype k isolates may be caused by a lack of
      expression of the gene involved in glucose side chain formation.

PMID- 16101967
TI  - Differential expression of chemokines and chemokine receptors in inflammatory
      periapical diseases.
AB  - BACKGROUND: Periapical lesions are thought to be the result of a local
      inflammatory response mediated by inflammatory cell infiltration and production
      of inflammatory mediators. Although chemokines are strongly implicated in the
      migration and activation of leukocytes in different inflammatory diseases and
      experimental models, little is known regarding the expression of chemokines and
      their receptors in human apical periodontitis. OBJECTIVE AND METHODS: The
      objective of this study was to determine the expression of chemokines and their
      receptors by real-time polymerase chain reaction in samples obtained from healthy
      gingiva, periapical granulomas, and inflammatory periradicular cysts. The
      inflammatory infiltrate was characterized by immunohistochemistry. RESULTS:
      Comparing cysts and granulomas, an increase in CD4+ and CD8+ cells was observed
      in granulomas, despite the similar numbers of CD45RO-positive cells detected in
      both lesions. The analysis of mRNA expression revealed increased levels of CCR1,
      CCR2, CCR3, CCR5, CXCR1, and CXCR3 in both types of lesion compared with
      controls. Cysts exhibited a higher expression of CCR3, CCR5, CXCR1, and CXCR3
      compared to granulomas. A significantly higher expression of RANTES, IP-10, and
      MCP-1 was detected in cysts compared with controls or granulomas. The expression
      of interleukin-8, MIP-1alpha, and MIP-1beta was not different in the three
      experimental groups. CONCLUSIONS: The increase in Th1 type (CCR1, CCR5, and
      CXCR3) and Th2 type (CCR2 and CCR3) receptors in both periapical lesions suggests
      the concomitant occurrence of Th1 and Th2 responses. Furthermore, the prevalent
      expression of the receptors CCR3, CCR5, CXCR1, and CXCR3 and of the chemokines
      RANTES, IP-10, and MCP-1 in cysts may point to a role in the progression of
      granulomas to cysts.

PMID- 16101968
TI  - Bacterial internalization in periodontitis.
AB  - BACKGROUND: Bacterial invasion of host epithelial cells plays an important role
      in the pathogenesis of periodontitis; however, the exact mechanism of the
      invasion has not been investigated. METHODS: Pocket epithelium biopsies in
      periodontitis were analysed via scanning and transmission electron microscopy
      using ultra-histochemical staining with ruthenium red for glycocalyx
      visualization. RESULTS: We demonstrated that oral bacteria adhered via fimbriae
      mediated adhesion only. The bacterial internalization in periodontitis was marked
      by the hallmark of the fimbriae-induced zipper mechanism--the phagocytic cup
      formation--but we found no sign of the trigger mechanism of internalization. In
      addition, we frequently observed apoptosis in the phagocytizing epithelial cells.
      CONCLUSION: Fimbriae-mediated adhesion is a prerequisite for bacterial invasion
      in periodontitis. This occurs by the fimbriae-induced zipper mechanism of
      internalization. As internalization induces apoptosis, the subsequent exfoliation
      might play a significant role in the clearance of periodontal pathogens.

PMID- 16101971
TI  - Ototoxic eardrops and tympanic membrane perforations: time for a change?
AB  - Until recently the only available antibiotic eardrops for treatment of the
      discharging middle ear and mastoid cavity have been potentially ototoxic. With
      the advent of non-ototoxic fluoroquinolone eardrops, consensus panels in the USA,
      Canada and the UK have advocated the preferential use of these agents in the open
      middle ear. However, in Australia, no fluoroquinolone topical agent is approved
      for use with tympanic membrane perforations, and when used as an 'off label'
      eardrop, none is on the Pharmaceutical Benefits Scheme. This creates an ethical
      dilemma, particularly with best practice management of chronic suppurative otitis
      media in indigenous children. Despite concerns regarding resistance issues with
      ototopical use of systemic antibiotics, bacterial resistance has not been
      documented in major studies. For equity and ethical reasons, Australian
      regulatory authorities should consider approving a sterile non-ototoxic eardrop
      for use in the open middle ear.

PMID- 16101972
TI  - Responding to diagnostic uncertainties of autistic spectrum disorders: facing the
      challenges.

PMID- 16101973
TI  - From complexity to category: responding to diagnostic uncertainties of autistic
      spectrum disorders.
AB  - OBJECTIVE: Recent data from Education Queensland has identified rising numbers of
      children receiving diagnoses of autistic spectrum disorder (ASD). Faced with
      funding diagnostic pressures, in clinical situations that are complex and
      inherently uncertain, it is possible that specialists err on the side of a
      positive diagnosis. This study examines the extent to which possible
      overinclusion of ASD diagnosis may exist in the presence of uncertainty and
      factors potentially related to this practice in Queensland. METHODS: Using
      anonymous self-report, all Queensland child psychiatrists and paediatricians who
      see paediatric patients with development/behavioural problems were surveyed and
      asked whether they had ever specified an ASD diagnosis in the presence of
      diagnostic uncertainty. Using logistic regression, elicited responses to the
      diagnostic uncertainty questions were related to other clinical- and practice
      related characteristics. RESULTS: Overall, 58% of surveyed psychiatrists and
      paediatricians indicated that, in the face of diagnostic uncertainty, they had
      erred on the side of providing an ASD diagnosis for educational ascertainment and
      36% of clinicians had provided an autism diagnosis for Carer's Allowance when
      Centrelink diagnostic specifications had not been met. CONCLUSION: In the absence
      of definitive biological markers, ASD remains a behavioural diagnosis that is
      often complex and uncertain. In response to systems that demand a categorical
      diagnostic response, specialists are providing ASD diagnoses, even when
      uncertain. The motivation for this practice appears to be a clinical risk/benefit
      analysis of what will achieve the best outcomes for children. It is likely that
      these practices will continue unless systems change eligibility to funding based
      on functional impairment rather than medical diagnostic categories.

PMID- 16101974
TI  - Diagnosis of autistic spectrum disorders in Queensland: variations in practice.
AB  - OBJECTIVE: For both paediatricians and child psychiatrists, referrals to assess
      possible autistic spectrum disorders (ASD) are increasing. This study examines
      current practices of medical specialists in the assessment of these disorders.
      METHODS: An anonymous, self-report questionnaire was sent to all Queensland
      paediatricians and child psychiatrists. The survey elicited frequencies of
      consultation for ASD, diagnostic method, advice provided and perceived adequacy
      of training for this work. RESULTS: Responses were received from 79 (85%)
      eligible paediatricians and 26 (58%) eligible child psychiatrists. For one-third
      of all clinicians, new consultations for possible ASD occurred as often as 2-3
      times per week. Most specialists approached the clinical diagnosis of ASD by
      considering history from different sources and professional assessments.
      Paediatricians (86%) were more likely than child psychiatrists (62%) to request
      genetic studies for children with severe autism (P = 0.01). Both general
      paediatricians and developmental paediatricians perceived level of training for
      possible ASD consultations was significantly worse than child psychiatrists (P <
      0.001 and P = 0.02, respectively), but no difference was found between paediatric
      groups (P = 0.27). Perceived adequacy of specialist training was not associated
      with length of experience in clinical practice. CONCLUSION: Medical practice in
      Queensland around diagnosis of ASD is characterized by considerable variability.
      There is still a long way to go if we are to achieve consistency around medical
      issues of organic diagnosis and practices impacting on health as well as
      consideration of differential developmental diagnoses. The finding that recently
      trained paediatricians felt just as unprepared for this work as their older
      colleagues suggests that the graduate training response to this 'new morbidity'
      has not been adequate.

PMID- 16101975
TI  - Vulnerable Baby Scale: development and piloting of a questionnaire to measure
      maternal perceptions of their baby's vulnerability.
AB  - OBJECTIVES: To develop and provide initial data to validate a contemporary
      measure of maternal perceptions of infant vulnerability. METHODS: Questions that
      address current concerns of mothers regarding their young children (such as the
      risk of sudden infant death syndrome) were added to an existing Vulnerable Child
      Questionnaire. Questions not relevant to either current concerns or to young
      infants were removed. The modified questionnaire, along with standard measures of
      maternal anxiety and depressive symptoms, were administered to mothers of 39
      healthy full-term babies, 17 mothers of 'medically fragile' babies and 19 mothers
      of jaundiced babies. Babies were approximately 12 weeks of age at the time of
      completion of the questionnaire. RESULTS: Three questions were removed from the
      questionnaire on the basis of poor item-total correlations, leaving the final
      version with 10 questions, scored on 1-5 rating scales. Cronbach alpha for the
      revised scale was 0.7. There was a significant difference (P = 0.002) in mean
      vulnerable baby scores between the control group and the 'medically fragile'
      group. There was a moderately strong correlation between vulnerable baby score
      and maternal state anxiety (r = 0.6) and a weaker correlation with maternal
      depressive symptoms (r = 0.3). CONCLUSIONS: The modified questionnaire has good
      internal consistency. The difference in mean scores between the three groups, and
      correlations with maternal anxiety and depressive symptoms, lend construct
      validity to the scale. The Vulnerable Baby Scale appears to be suitable for
      assessing maternal perceptions of the vulnerability of their young babies in
      clinical and research settings although further research, with larger samples,
      may be necessary to fully establish the scale's psychometric properties.

PMID- 16101976
TI  - Survey of complementary and alternative medicine use at a tertiary children's
      hospital.
AB  - OBJECTIVE: The use of complementary and alternative medicine (CAM) within the
      Australian community is common. The objective of this study was to determine the
      prevalence and pattern of CAM usage in children attending a tertiary children's
      hospital. METHODS: We conducted a cross-sectional survey of children attending
      the Royal Children's Hospital, Melbourne. Children were identified by consecutive
      acute admissions and attendance at outpatient clinics. A structured questionnaire
      with items about the use of CAM in the preceding year was administered by means
      of a face-to-face interview. RESULTS: Based on the 503 children surveyed, 51%
      reported CAM use in the preceding year. Forty-three percent had used at least one
      CAM medication. The most common medicinal CAM used were multivitamins, vitamin C,
      herbal remedies and homeopathic treatments. Non-medicinal CAM was used by 23% of
      the participants. The most commonly used therapies were chiropractic,
      naturopathy, aromatherapy, therapeutic massage and dietary restriction. The main
      reasons stated for CAM usage included promotion of general health and treatment
      of colds. Sixty-three percent of those reporting CAM use had not discussed this
      with their treating doctor. CONCLUSION: The use of CAM by children is common.
      Complementary and alternative medicine is particularly used for the treatment of
      common illnesses and conditions of childhood. Importantly, use is not always
      conveyed to treating physicians. Given the potential risk of adverse events
      associated with the use of CAM or interactions with conventional management,
      doctors should ask about their use as a part of routine history taking.

PMID- 16101977
TI  - Pulmonary aspiration of gastric contents and the sudden infant death syndrome.
AB  - OBJECTIVE: To determine ante-mortem and post-mortem risk factors for the finding
      of gastric contents in pulmonary airways (aspiration of gastric contents) at post
      mortem examination in the sudden infant death syndrome (SIDS). METHODS: There
      were 217 post-neonatal deaths in the Auckland region of the New Zealand Cot Death
      Study. No deaths were certified as due to aspiration of gastric contents. There
      were 138 SIDS cases. The parents of 110 (80%) of these cases were interviewed.
      Histological sections from the periphery of the lungs in 99 of the 110 cases were
      reviewed for evidence of aspiration of gastric contents. A wide range of
      variables were analysed in SIDS cases with and without aspiration to determine
      risk factors. RESULTS: Aspiration of gastric contents was identified in 37 (37%)
      of SIDS cases. Aspiration was of mild-to-moderate degree and in no case was
      severe and a potential cause of death. Finding infants on their backs at death (P
      = 0.024) and conducting the post-mortem on the day after the death or
      subsequently (P = 0.033) were statistically significant variables linked to
      identification of aspiration. Position placed to sleep, symptoms of gastro
      oesophageal reflux and other variables were not related to aspiration.
      CONCLUSIONS: The only determinants for aspiration of gastric contents identified
      were agonal or post-mortem events, supporting the contention that aspiration has
      limited relevance to the mechanism of SIDS.

PMID- 16101978
TI  - Inpatient care of children with cerebral palsy as perceived by their parents.
AB  - OBJECTIVES: Children with cerebral palsy (CP) have special health care needs. The
      aim of the study was to evaluate the inpatient care of children with CP, as
      perceived by their parents. METHODS: Forty parents of children with CP and 90
      parents of able-bodied children completed a questionnaire designed to evaluate
      their perception of their child's hospital admission, including the care
      provided. The parents also completed the Perceived Stress Scale. RESULTS:
      Overall, parents of able-bodied children were more satisfied with the
      hospitalization than parents of children with CP (P < 0.0001). Significant
      differences were found in four of the five areas assessed: the admissions process
      (P = 0.0002); the care that their child received (P < 0.0001); their
      communication and confidence in doctors and nurses (P < 0.0001); and their
      personal experience of the hospital (P = 0.0076). Parents of disabled children
      displayed a much higher mean score on the Perceived Stress Scale, but no
      correlation was found between this scale and the satisfaction questionnaire for
      either group. CONCLUSION: The results of this study show that parents of children
      with CP were, as a group, less satisfied than parents of able-bodied children
      with their inpatient experience. Although these children have complex needs and
      often require more care than able-bodied children, it is imperative that their
      needs are met and that parents are satisfied with all aspects of the care they
      receive in hospital.

PMID- 16101979
TI  - Diagnosing symptomatic urinary tract infections in infants by catheter urine
      culture.
AB  - BACKGROUND: Diagnosing infantile urinary tract infection (UTI) is difficult due
      to contamination during urine collection. Catheterization is convenient but
      diagnostic criteria (colony-forming units per millilitre (CFU/mL)) is
      controversial, especially in uncircumcised males. OBJECTIVES: To study the value
      of catheter urine cultures in terms of likelihood ratios (LRs), sensitivity,
      specificity, positive and negative predictive values of different CFU/mL in
      uncircumcised boys and girls. METHODS: Infants aged 1-18 months who had catheter
      urine cultures from July 1999 to June 2002 were reviewed to decide if they had
      symptomatic UTI (group A) or not (group B). Urinary tract infection was confirmed
      if patients had a positive urine culture plus acute fever, pyuria, positive
      leucocyte esterase and nitrite tests and good response to antibiotics, with
      pyelonephritic evidence on early dimercaptosuccinic acid (DMSA) scans in doubtful
      cases. Group B included infants with negative urine culture results, and those
      with positive results but were asymptomatic and admitted for micturating
      cystourethrogram. RESULTS: Nine hundred and fifty-two patients were studied (492
      boys, 460 girls; 212 in group A, 740 in group B). No single cut-off CFU/mL has
      high sensitivity and specificity to simultaneously diagnose and exclude UTI. The
      CFU counts of 100-10(3), 10(3)-10(4), 10(4)-10(5) and >10(5) were associated with
      LRs of 0.11, 0.45, 1.52 and 20.5, respectively in uncircumcised boys, and with
      LRs of 1.39, 2.49, 8.95 and 18.8, respectively in girls. The LR for mixed growths
      was 0.21. CONCLUSION: Unlike suprapubic tap urine, catheter urine culture has to
      be interpreted against the clinical context or pretest probability and in terms
      of probability. In the scenario of a febrile infant where the pretest probability
      of UTI was about 5%, UTI was highly likely if counts exceeded 10(5)/mL, and
      unlikely if counts were below 10(4)/mL in uncircumcised boys. In female infants,
      UTI was highly likely if counts were >10(4) CFU/mL, but lower counts could not
      exclude UTI.

PMID- 16101980
TI  - Adverse reactions to immunization with newer vaccines in the very preterm infant.
AB  - OBJECTIVE: To study the frequency and types of adverse reactions to currently
      available vaccines in very preterm infants. METHODS: Case notes were obtained for
      very preterm infants < or =30 weeks' gestational age who received their first
      immunization at the Royal Women's Hospital, Melbourne, during 1999-2003. Data
      were extracted for the time periods 48 h before and 48 h after immunizations,
      with the data extraction blinded as to whether the period being evaluated was pre
      or post-immunization. Data collected focused on the frequency and severity of
      apnoea, respiratory support, fever and clinical consequences of adverse
      reactions. RESULTS: A total of 48 very preterm infants were immunized during the
      period; 37 infants had Comvax (Haemophilus influenzae type B and hepatitis B
      vaccine), Infanrix (diphtheria, tetanus and acellular pertussis vaccine) and
      inactivated poliomyelitis vaccine, and 11 infants had Comvax and Infanrix only.
      Their mean (SD) gestational age at birth was 26.4 (1.7) weeks with mean
      birthweight of 872 (235) g. The mean postnatal age at immunization was 76 (20)
      days. Low-grade fever (>37.5 degrees C per axilla) occurred in 16 (33%) infants
      after immunization, but none before immunization (P < 0.001). There was no
      substantial change in recorded apnoea. No serious adverse events were noted. Four
      (8%) infants underwent a septic work up post-immunization. The C-reactive protein
      was increased in all four infants, but other tests for sepsis were negative.
      CONCLUSION: Fever remains a common adverse event following immunization of the
      preterm infant in spite of the development of a new generation of vaccines.

PMID- 16101981
TI  - Developmental assessment of children: a survey of Australian and New Zealand
      paediatricians.
AB  - OBJECTIVES: To determine the current practice for developmental assessment of
      children by Australian and New Zealand paediatricians. To determine factors
      associated with higher levels of self-reported confidence and expertise in
      developmental paediatrics and factors associated with better practice. METHODS: A
      cross-sectional postal survey of Australian and New Zealand paediatricians
      conducted in 2003, enquiring about their training in developmental paediatrics
      and their practice for evaluating development. RESULTS: Of 811 questionnaires
      sent, 590 (73%) were returned. Ninety-one respondents indicated that they did not
      see children with developmental issues leaving 499 surveys for analysis. The
      overwhelming majority of paediatricians felt that more training was required in
      developmental paediatrics (88%) and that there was a need to be taught a formal
      developmental assessment tool (83%). Higher self-ratings of confidence and
      expertise in developmental paediatrics were associated with a period of formal
      developmental training (OR (95% CI) 2.7 (1.6-4.4), 3.4 (2.0-5.8), respectively),
      and being taught a formal developmental assessment tool (OR (95% CI) 2.0 (1.2
      3.2), 2.2 (1.3-3.7), respectively). Predictors of paediatricians performing a
      formal developmental assessment included formal developmental training (OR (95%
      CI) 2.0 (1.1-3.8)) being taught an assessment tool (OR (95% CI) 2.8 (1.5-5.2))
      and mandatory training (OR (95% CI) 2.4 (1.4-4.1)). CONCLUSIONS: Developmental
      paediatrics is a significant and important part of paediatric practice. This
      survey suggests, however, that paediatric training and continuing education
      should have not reflected this practice. The overall method and content of
      developmental training including whether formal assessment tools should be taught
      needs to be reviewed and revised.

PMID- 16101982
TI  - Symptomatic infant characteristics of congenital cytomegalovirus disease in
      Australia.
AB  - BACKGROUND: Human cytomegalovirus (CMV) is the most common cause of viral
      intrauterine infection. In utero transmission can occur during primary maternal
      infection, reactivation or reinfection of seropositive mothers. OBJECTIVE: To
      describe the aetiology and clinical features of infants diagnosed with congenital
      CMV and to document maternal factors that were presented. METHODS: Active
      national surveillance was initiated in 1999 in collaboration with the Australian
      Paediatric Surveillance Unit. RESULTS: Monthly notifications resulted in 70 cases
      of congenital CMV being identified between 1999 and 2003. Nearly all of the cases
      were symptomatic with the most common clinical sequelae reported in infected
      infants being jaundice, thrombocytopaenia, hepatomegaly, petechiae, purpura and
      splenomegaly. Almost half (43.5%) of the infants had central nervous system (CNS)
      complications, such as microcephaly, chorioretinitis, sensorineural hearing loss,
      intracranial calcifications, developmental delay or seizures, with over half
      presenting two or more CNS abnormalities. Maternal febrile illness was noted in
      54.8% of the cases. The majority of mothers were primiparous (46.4%) or
      secundiparous (39.3%), indicating two different population groups at risk of
      primary CMV infection. CONCLUSION: This study documents symptomatic congenital
      CMV cases in Australia.

PMID- 16101983
TI  - Rebecca's story.

PMID- 16101984
TI  - Subcutaneous emphysema of the posterior chest wall in a neonate.

PMID- 16101985
TI  - Severe hypernatraemic dehydration in a breast-fed neonate.

PMID- 16101986
TI  - Re: transverse myelitis after measles and rubella vaccination.

PMID- 16101993
TI  - Taking shape: control of bacterial cell wall biosynthesis.
AB  - The characteristic shape of a bacterial cell is a function of the three
      dimensional architectures of the cell envelope and is determined by the balance
      between lateral wall extension and synthesis of peptidoglycan at the division
      septum. The three dimensional patterns of cell wall synthesis in the bacterium
      Bacillus subtilis is influenced by actin-like proteins that form helical coils in
      the cell and by the MreCD membrane proteins that link the cytoskeletal elements
      with the penicillin-binding proteins that carry out peptidoglycan synthesis.
      Recent genetic studies have provided important clues as to how these proteins are
      arranged in the cell and how they function to regulate cell shape.

PMID- 16101994
TI  - Solving a sticky problem: new genetic approaches to host cell adhesion by the
      Lyme disease spirochete.
AB  - The Lyme disease spirochetes, comprised of at least three closely related
      species, Borrelia burgdorferi, Borrelia garinii and Borrelia afzelii, are
      fascinating and enigmatic bacterial pathogens. They are maintained by tick
      mediated transmission between mammalian hosts, usually small rodents. The ability
      of these bacteria, which have relatively small genomes, to survive and
      disseminate in both an immunocompetent mammal and in an arthropod vector suggests
      that they have evolved elegant and indispensable strategies for interacting with
      their hosts. Recognition of specific mammalian and tick tissues is likely to be
      essential for successful completion of the enzootic life cycle but, given the
      historical difficulties in genetic manipulation of these organisms,
      characterization of factors promoting cell adhesion has until recently largely
      been confined to either the manipulation of host cells or the analysis of
      potential bacterial ligands in the form of recombinant proteins. These studies
      have led to the identification of several mammalian receptors for Lyme disease
      spirochetes, including glycosaminoglycans, decorin, fibronectin and integrins, as
      well as a tick receptor for the bacterium, and also candidate cognate bacterial
      ligands. Recent advances in our ability to genetically manipulate Lyme disease
      spirochetes, particularly B. burgdorferi, are now providing us with firm evidence
      that these ligands indeed do promote bacterial adherence to host cells, and with
      new insights into the roles of these multifacted Borrelia-host cell interactions
      during mammalian and arthropod infection.

PMID- 16101995
TI  - Roles for MreC and MreD proteins in helical growth of the cylindrical cell wall
      in Bacillus subtilis.
AB  - Actin homologues of the MreB family have an important role in specifying the
      morphology of many non-spherical eubacteria. The mreC and mreD genes have been
      implicated in control of cell morphology but their precise functions are unknown.
      In Bacillus subtilis the MreB homologue Mbl directs helical insertion of new cell
      wall material in the cylindrical part of the rod-shaped cell. Depletion of either
      MreC or MreD abolishes the control of cell shape. In the presence of high
      concentrations of magnesium cells depleted of MreC or MreD can be propagated
      indefinitely, although they have a spheroidal shape. We show that growth of the
      spheroidal mutants is based on insertion of new wall material at cell division
      sites and that this localized growth is dependent on cell division. Under some
      conditions the MreC and MreD proteins localize in a helical configuration. This
      localization pattern resembles that of the helical cables of Mbl protein. These
      results suggest that MreC and MreD act in a morphogenic pathway that couples the
      helical cytosolic Mbl cables to the extracellular cell wall synthetic machinery,
      which is critical for cylindrical elongation of the rod-shaped cells.

PMID- 16101996
TI  - Rhamnolipids mediate detachment of Pseudomonas aeruginosa from biofilms.
AB  - The process of detachment, through which bacteria use active mechanisms to leave
      biofilms and return to the planktonic (free-living) state, is perhaps the least
      understood aspect of the biofilm life cycle. Like other stages of biofilm
      development, detachment is a dynamic, regulated process, controlled by specific
      genes, and induced by particular environmental cues. In previous work we
      discovered Pseudomonas aeruginosa variants that exhibit accelerated biofilm
      detachment. These hyper-detaching variants arise spontaneously from biofilms at a
      high frequency, and they exhibit robust detachment under different biofilm growth
      conditions. Here we show that these variants detach by a mechanism requiring the
      biosurfactant rhamnolipid and that this detachment mechanism rapidly restores
      antibiotic sensitivity to separating bacteria. We also show that rhamnolipids can
      bring about detachment in wild-type P. aeruginosa biofilms. These findings raise
      the possibility that this detachment mechanism may be useful as a treatment to
      disrupt established biofilms. Interestingly, the rhamnolipid-mediated detachment
      mechanism involves the formation of cavities within the centre of biofilm
      structures. Our data suggest a model to explain detachment that occurs via this
      pattern.

PMID- 16101997
TI  - MHP1, a Magnaporthe grisea hydrophobin gene, is required for fungal development
      and plant colonization.
AB  - Fungal hydrophobins are implicated in cell morphogenesis and pathogenicity in
      several plant pathogenic fungi including the rice blast fungus Magnaporthe
      grisea. A cDNA clone encoding a hydrophobin (magnaporin, MHP1) was isolated from
      a cDNA library constructed from rice leaves infected by M. grisea. The MHP1 codes
      for a typical fungal hydrophobin of 102 amino acids containing eight cysteine
      residues spaced in a conserved pattern. Hydropathy analysis of amino acids
      revealed that MHP1 belongs to the class II group of hydrophobins. The amino acid
      sequence of MHP1 exhibited about 20% similarity to MPG1, an M. grisea class I
      hydrophobin. Expression of MHP1 was highly induced during plant colonization and
      conidiation, but could hardly be detected during mycelial growth. Transformants
      in which MHP1 was inactivated by targeted gene replacement showed a detergent
      wettable phenotype, but were not altered in wettability with water. mhp1 mutants
      also exhibited pleiotropic effects on fungal morphogenesis, including reduction
      in conidiation, conidial germination, appressorium development and infectious
      growth in host cells. Furthermore, conidia of mhp1 mutants were defective in
      their cellular organelles and rapidly lose viability. As a result, mhp1 mutants
      exhibited a reduced ability to infect and colonize a susceptible rice cultivar.
      These phenotypes were recovered by re-introduction of an intact copy of MHP1.
      Taken together, these results indicate that MHP1 has essential roles in surface
      hydrophobicity and infection-related fungal development, and is required for
      pathogenicity of M. grisea.

PMID- 16101998
TI  - The penC mutation conferring antibiotic resistance in Neisseria gonorrhoeae
      arises from a mutation in the PilQ secretin that interferes with multimer
      stability.
AB  - The penC resistance gene was previously characterized in an FA19 penA mtrR penB
      gonococcal strain (PR100) as a spontaneous mutation that increased resistance to
      penicillin and tetracycline. We show here that antibiotic resistance mediated by
      penC is the result of a Glu-666 to Lys missense mutation in the pilQ gene that
      interferes with the formation of the SDS-resistant high-molecular-mass PilQ
      secretin complex, disrupts piliation and decreases transformation frequency by 50
      fold. Deletion of pilQ in PR100 confers the same level of antibiotic resistance
      as the penC mutation, but increased resistance was observed only in strains
      containing the mtrR and penB resistance determinants. Site-saturation mutagenesis
      of Glu-666 revealed that only acidic or amidated amino acids at this position
      preserved PilQ function. Consistent with early studies suggesting the importance
      of cysteine residues for stability of the PilQ multimer, mutation of either of
      the two cysteine residues in FA19 PilQ led to a similar phenotype as penC:
      increased antibiotic resistance, loss of piliation, intermediate levels of
      transformation competence and absence of SDS-resistant PilQ oligomers. These data
      show that a functional secretin complex can enhance the entry of antibiotics into
      the cell and suggest that the PilQ oligomer forms a pore in the outer membrane
      through which antibiotics diffuse into the periplasm.

PMID- 16101999
TI  - A master regulator sigmaB governs osmotic and oxidative response as well as
      differentiation via a network of sigma factors in Streptomyces coelicolor.
AB  - The differentiating bacterium Streptomyces coelicolor harbours some 66 sigma
      factors, which support its complex life cycle. sigma(B), a functional homologue
      of sigma(S) from Escherichia coli, controls both osmoprotection and
      differentiation in S. coelicolor A3(2). Microarray analysis revealed sigma(B)
      dependent induction of more than 280 genes by 0.2 M KCl. These genes encode
      several sigma factors, oxidative defence proteins, chaperones, systems to provide
      osmolytes, cysteine, mycothiol, and gas vesicle. sigma(B) controlled induction of
      itself and its two paralogues (sigma(L) and sigma(M)) in a hierarchical order of
      sigma(B)-->sigma(L)-->sigma(M), as revealed by S1 mapping and Western blot
      analyses. The phenotype of each sigma mutant suggested a sequential action in
      morphological differentiation; sigma(B) in forming aerial mycelium, sigma(L) in
      forming spores and sigma(M) for efficient sporulation. sigma(B) was also
      responsible for the increase in cysteine and mycothiol, the major thiol buffer in
      actinomycetes, upon osmotic shock, revealing an overlap between protections
      against osmotic and oxidative stresses. Proteins in sigB mutant were more
      oxidized (carbonylated) than the wild type. These results support a hypothesis
      that sigma(B) serves as a master regulator that triggers other related sigma
      factors in a cascade, and thus regulates differentiation and osmotic and
      oxidative response in S. coelicolor.

PMID- 16102000
TI  - Characterization of the molecular mechanisms involved in the differential
      production of erythrose-4-phosphate dehydrogenase, 3-phosphoglycerate kinase and
      class II fructose-1,6-bisphosphate aldolase in Escherichia coli.
AB  - A gapA-pgk gene tandem coding the glyceraldehyde 3-phosphate dehydrogenase and 3
      phosphoglycerate kinase, is most frequently found in bacteria. However, in
      Enterobacteriaceae, gapA is replaced by an epd open reading frame (ORF) coding an
      erythrose-4-phosphate dehydrogenase and an fbaA ORF coding the class II fructose
      1,6-bisphosphate aldolase follows pgk. Although epd expression is very low in
      Escherichia coli, we show that, in the presence of glucose, the 3 epd, pgk and
      fbaA ORFs are efficiently cotranscribed from promoter epd P0. Conservation of
      promoter epd P0 is likely due to its important role in modulation of the
      metabolic flux during glycolysis and gluconeogenesis. As a consequence, we found
      that the epd translation initiation region and ORF have been adapted in order to
      limit epd translation and to create an efficient RNase E entry site. We also show
      that fbaA is cotranscribed with pgk, from promoter epd P0 or an internal pgk P1
      promoter of the extended -10 class. The differential expression of pgk and fbaA
      also depends upon an RNase E segmentation process, leading to individual mRNAs
      with different stabilities. The secondary structures of the RNA regions
      containing the RNase E sites were experimentally determined which brings
      important information on the structural features of RNase E ectopic sites.

PMID- 16102001
TI  - Evidence that WbpD is an N-acetyltransferase belonging to the hexapeptide
      acyltransferase superfamily and an important protein for O-antigen biosynthesis
      in Pseudomonas aeruginosa PAO1.
AB  - Di-N-acetylated uronic acid residues are unique sugar moieties observed in the
      lipopolysaccharides (LPS) of respiratory pathogens including several serotypes of
      Pseudomonas aeruginosa and several species of Bordetella. WbpD of P. aeruginosa
      PAO1 (serotype O5) is a putative 3-N-acetyltransferase that has been implicated
      in the biosynthesis of UDP-2,3-diacetamido-2,3-dideoxy-d-mannuronic acid [UDP-d
      Man(2NAc3NAc)A], a precursor for the d-Man(2NAc3NAc)A residues in the B-band O
      antigen of this bacterium. A chromosomal knockout mutant of wbpD is incapable of
      producing either long-chain B-band O antigen (> or = 2 repeating units) or semi
      rough LPS (lipid A-core + one repeat). Adding wbpD in trans restored LPS
      production to the wild-type level; this indicates that wbpD is important for
      biosynthesis of individual B-band O-antigen repeating units. WbpD contains left
      handed beta-helical (LbetaH) structure as observed by Conserved Domain analysis
      and in silico secondary and tertiary structure predictions. This feature
      suggested that WbpD belongs to the hexapeptide acyltransferase (HexAT)
      superfamily of enzymes. WbpD was overexpressed as an N-terminally histidine
      tagged fusion protein (His6-WbpD) and purified to > 95% purity. The protein was
      subjected to Far-UV circular dichroism spectroscopy, and the data revealed that
      WbpD contains left-handed helical structure, which substantiated in silico
      predictions made earlier. Results from SDS-PAGE, matrix-assisted laser
      desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS), and gel
      filtration analyses indicated that His6-WbpD has trimeric organization,
      consistent with the quaternary structure of HexATs. The binding of acetyl-CoA by
      WbpD was demonstrated by MALDI-TOF MS, suggesting that WbpD is an
      acetyltransferase that utilizes a direct-transfer reaction mechanism. Incubation
      of WbpD with acetyl-CoA significantly enhanced the stability of the protein and
      prevented precipitation over a course of 14 days. As a substrate for studying the
      enzymatic activity of WbpD is unavailable at present, a structure-based model for
      the LbetaH domain of WbpD was generated. Comparisons between this model and the
      LbetaH domains of known HexATs suggested that Lys136 plays a role in acetyl-CoA
      binding. A K136A site-directed mutant construct could only partially complement
      the wbpD knockout, and this mutation also reduced the stabilizing effects of
      acetyl-CoA, while a K136R mutation showed no discernible effect on
      complementation of the wbpD mutant or the stabilizing effects of acetyl-CoA on
      the purified mutant protein. A modified pathway was proposed for the biosynthesis
      of UDP-d-Man(2NAc3NAc)A, in which WbpD is involved in the catalysis of the fourth
      step by acting as a UDP-2-acetamido-3-amino-2,3-dideoxy-d-glucuronic acid 3-N
      acetyltransferase.

PMID- 16102002
TI  - NopP, a phosphorylated effector of Rhizobium sp. strain NGR234, is a major
      determinant of nodulation of the tropical legumes Flemingia congesta and
      Tephrosia vogelii.
AB  - Rhizobium sp. NGR234 nodulates many plants, some of which react to proteins
      secreted via a type three secretion system (T3SS) in a positive- (Flemingia
      congesta, Tephrosia vogelii) or negative- (Crotalaria juncea, Pachyrhizus
      tuberosus) manner. T3SSs are devices that Gram-negative bacteria use to inject
      effector proteins into the cytoplasm of eukaryotic cells. The only two rhizobial
      T3SS effector proteins characterized to date are NopL and NopP of NGR234. NopL
      can be phosphorylated by plant kinases and we show this to be true for NopP as
      well. Mutation of nopP leads to a dramatic reduction in nodule numbers on F.
      congesta and T. vogelii. Concomitant mutation of nopL and nopP further diminishes
      nodulation capacity to levels that, on T. vogelii, are lower than those produced
      by the T3SS null mutant NGR(Omega)rhcN. We also show that the T3SS of NGR234
      secretes at least one additional effector, which remains to be identified. In
      other words, NGR234 secretes a cocktail of effectors, some of which have positive
      effects on nodulation of certain plants while others are perceived negatively and
      block nodulation. NopL and NopP are two components of this mix that extend the
      ability of NGR234 to nodulate certain legumes.

PMID- 16102003
TI  - The moonlighting protein Tsa1p is implicated in oxidative stress response and in
      cell wall biogenesis in Candida albicans.
AB  - Candida albicans is one of the most common fungal pathogens in humans. The cell
      wall is the first contact site between host and pathogen and thus is critical for
      colonization and infection of the host. We have identified Tsa1p, a protein that
      is differentially localized to the cell wall of C. albicans in hyphal cells but
      remains in the cytosol and nucleus in yeast-form cells. This is different from
      Saccharomyces cerevisiae, where the homologous protein solely has been found in
      the cytoplasm. We report here that TSA1 confers resistance towards oxidative
      stress as well as is involved in the correct composition of hyphal cell walls.
      However, no significant change of the cell wall composition was observed in a
      TSA1 deletion strain in yeast-form cells, which is in good agreement with the
      observation that Tsa1p is absent from the yeast-form cell wall. This indicates
      that Tsa1p of C. albicans might represent a moonlighting protein with specific
      functions correlating to its respective localization. Furthermore, the
      translocation of Tsa1p to the hyphal cell wall of C. albicans depends on Efg1p,
      suggesting a contribution of the cAMP/PKA pathway to the localization of this
      protein. In a strain deleted for TUP1 that filaments constitutively Tsa1p can be
      found in the cell wall under all conditions tested, confirming the result that
      Tsa1p localization to the cell wall is correlated to the morphology of C.
      albicans.

PMID- 16102004
TI  - Distinct mechanisms govern proteolytic shedding of a key invasion protein in
      apicomplexan pathogens.
AB  - Apical membrane antigen-1 (AMA1) is a conserved apicomplexan protein that plays
      an important but undefined role in host cell invasion. We have studied the fate
      of Plasmodium falciparum AMA1 (PfAMA1) during erythrocyte invasion by the malaria
      merozoite, and compared it with that of the Toxoplasma gondii orthologue, TgAMA1.
      Shedding of the PfAMA1 ectodomain goes essentially to completion during invasion,
      and occurs predominantly or exclusively via juxtamembrane cleavage at the
      previously identified sheddase cleavage site, Thr517. Only the resulting
      juxtamembrane stub of the ectodomain is efficiently carried into the host cell,
      and this remains distributed around the plasma membrane of the intracellular ring
      stage parasite. Inhibition of normal shedding, however, results in proteolysis at
      an intramembrane, rhomboid-like cleavage site, and PfAMA1 is susceptible to
      cleavage by Drosophila rhomboid-1, showing that it can be a substrate for
      intramembrane cleavage but is not normally processed in this manner. In contrast,
      shedding of TgAMA1 from the surface of extracellular tachyzoites occurs
      exclusively via cleavage within the luminal half of its transmembrane domain by a
      rhomboid-like protease. Also unlike PfAMA1, complete TgAMA1 shedding does not
      accompany Toxoplasma invasion as the intact protein was readily detected on the
      surface of newly invaded tachyzoites. This work reveals unexpected differences in
      the manner in which Plasmodium and Toxoplasma shed AMA1 from the surface of
      invasive zoites, and demonstrates the presence at the malaria merozoite surface
      of a rhomboid-like protease.

PMID- 16102005
TI  - The alpha-toxin of Clostridium septicum is essential for virulence.
AB  - Clostridium septicum is the causative agent of spontaneous gas gangrene or
      atraumatic myonecrosis, a sudden and frequently fatal infection that is
      increasingly associated with malignancy of the colon. Little is known about the
      disease process although the focus of virulence studies has been the alpha-toxin,
      a pore-forming cytolysin that is encoded by the csa gene and secreted as an
      inactive protoxin. Until now a lack of techniques for the genetic manipulation of
      C. septicum has hindered the use of molecular approaches to understand
      pathogenesis. By introducing plasmids by conjugation from Escherichia coli, we
      have developed methods for the genetic manipulation of C. septicum and
      constructed a chromosomal csa mutant by allelic exchange. Virulence testing of an
      isogenic series of strains consisting of the wild type, the csa mutant, and a csa
      mutant complemented with the wild-type csa gene revealed that the development of
      fulminant myonecrosis in mice was dependent on the ability to produce a
      functional haemolytic alpha-toxin. Furthermore, the inhibition of leukocyte
      influx into the lesion, which is very typical of clostridial myonecrosis, was
      also dependent on the ability to produce alpha-toxin. This study represents the
      first definitive identification of a virulence factor in this organism and opens
      the way for further studies that will delineate the role of other putative
      virulence factors in this significant pathogen.

PMID- 16102006
TI  - VirR, a response regulator critical for Listeria monocytogenes virulence.
AB  - Signature-tagged mutagenesis (STM) was used to identify new genes involved in the
      virulence of the Gram-positive intracellular pathogen Listeria monocytogenes. One
      of the mutants isolated by this technique had the transposon inserted in virR, a
      gene encoding a putative response regulator of a two-component system. Deletion
      of virR severely decreased virulence in mice as well as invasion in cell-culture
      experiments. Using a transcriptomic approach, we identified 12 genes regulated by
      VirR, including the dlt-operon, previously reported to be important for L.
      monocytogenes virulence. However, a strain lacking dltA, was not as impaired in
      virulence as the DeltavirR strain, suggesting a role in virulence for other
      members of the vir regulon. Another VirR-regulated gene is homologous to mprF,
      which encodes a protein that modifies membrane phosphatidyl glycerol with l
      lysine and that is involved in resistance to human defensins in Staphylococcus
      aureus. VirR thus appears to control virulence by a global regulation of surface
      components modifications. These modifications may affect interactions with host
      cells, including components of the innate immune system. Surprisingly, although
      controlling the same set of genes as VirR, the putative cognate histidine kinase
      of VirR, VirS, encoded by a gene located three genes downstream of virR, was
      shown not to be essential for virulence. By monitoring the activity of VirR with
      a GFP reporter construct, we showed that VirR can be activated independently of
      VirS, for example through a mechanism involving variations in the level of
      intracellular acetyl phosphate. In silico analysis of the VirR-regulated
      promoters revealed a VirR DNA-binding consensus site and specific interaction
      between purified VirR protein and this consensus sequence was demonstrated by gel
      mobility shift assays. This study identifies a second key virulence regulon in L.
      monocytogenes, after the prfA regulon.

PMID- 16102007
TI  - Novel gene functions required for melanization of the human pathogen Cryptococcus
      neoformans.
AB  - The ability to produce melanin is a key virulence factor in many fungal pathogens
      including the human basidiomycete pathogen Cryptococcus neoformans, a major cause
      of life-threatening infections among immunocompromised persons. Despite the
      significance of melanin biosynthesis in virulence of C. neoformans, the cellular
      and molecular processes involved in this pathway have not yet been fully
      elucidated. Here, we used Agrobacterium to isolate insertional mutants and
      screened 12 000 mutants to uncover genes involved in melanin production in C.
      neoformans. Four new mutant alleles of the well-known melanin biosynthesis gene,
      LAC1, which encodes laccase were identified, and the T-DNA was shown to have a
      possible predisposition for insertion into the promoters of genes, in particular
      LAC1. Melanization in C. neoformans is dependent on five additional genes
      identified in this screen encoding homologues of the copper transporter Ccc2, the
      copper chaperone Atx1, the chitin synthase Chs3, the transcriptional coactivator
      Mbf1 and the chromatin-remodelling enzyme Snf5. Illumination of the molecular and
      genetic components of this virulence pathway reveals potential novel targets for
      drug development against C. neoformans and provides further insight into the
      intimate relationship between metal ion homeostasis and melanin biosynthesis.

PMID- 16102008
TI  - Residues that influence in vivo and in vitro CbbR function in Rhodobacter
      sphaeroides and identification of a specific region critical for co-inducer
      recognition.
AB  - CbbR is a LysR-type transcriptional regulator (LTTR) that is required to activate
      transcription of the cbb operons, responsible for CO2 fixation, in Rhodobacter
      sphaeroides. LTTR proteins often require a co-inducer to regulate transcription.
      Previous studies suggested that ribulose 1,5-bisphosphate (RuBP) is a positive
      effector for CbbR function in this organism. In the current study, RuBP was found
      to increase the electrophoretic mobility of the CbbR/cbb(I) promoter complex. To
      define and analyse the co-inducer recognition region of CbbR, constitutively
      active mutant CbbR proteins were isolated. Under growth conditions that normally
      maintain transcriptionally inactive cbb operons, the mutant CbbR proteins
      activated transcription. Fourteen of the constitutively active mutants resulted
      from a single amino acid substitution. One mutant was derived from amino acid
      substitutions at two separate residues that appeared to act synergistically.
      Different mutant proteins showed both sensitivity and insensitivity to RuBP and
      residues that conferred constitutive transcriptional activity could be
      highlighted on a three-dimensional model, with several residues unique to CbbR
      shown to be at locations critical to LTTR function. Many of the constitutive
      residues clustered in or near two specific loops in the LTTR tertiary structure,
      corresponding to a proposed site of co-inducer binding.

PMID- 16102009
TI  - Secretion of YscP from Yersinia enterocolitica is essential to control the length
      of the injectisome needle but not to change the type III secretion substrate
      specificity.
AB  - The length of the needle of the Yersinia Ysc injectisome is determined by a
      protein called YscP. This protein, which acts both as a molecular ruler and as a
      substrate-specificity switch for type III secretion is itself secreted by the
      injectisome. In this report, we address the question why YscP is secreted. By a
      systematic deletion analysis and by fusing different parts of the molecule to the
      adenylate cyclase reporter, we identified two independent secretion signals. One
      of them is encompassed within the 35 N-terminal residues while the second one
      spans residues 97-137. These two signals are functionally different from Yop
      secretion signals. When both secretion signals were removed, Yops could still be
      secreted but the needle length control was lost. YscP possessing only one signal
      did not control needle length properly but the control was improved when more
      YscP was produced and secreted. YscP deprived of both signals could not control
      length, even when overproduced. We conclude from this that YscP needs to be
      secreted to exert its length control function but not its substrate-specificity
      switch function.

PMID- 16102010
TI  - A novel DNA modification by sulphur.
AB  - Streptomyces lividans has a novel DNA modification, which sensitises its DNA to
      degradation during electrophoresis (the Dnd phenotype). The entire gene cluster
      (dnd) involved in this modification was localized on an 8 kb DNA fragment and was
      expressed in a S. lividans deletion mutant (dnd) and in several heterologous
      hosts. Disruption of the dnd locus abolishes the Dnd phenotype, and gain of the
      dnd locus conferred the Dnd phenotype respectively. Extensive analysis of the dnd
      gene cluster revealed five open reading frames, whose hypothetic functions
      suggested an incorporation of sulphur or a sulphur-containing substance into S.
      lividans genome, yet in an unknown manner. The Dnd phenotype was also discovered
      to exist in DNA of widespread bacterial species of variable origin and diverse
      habitat. Similarly organized gene clusters were found in several bacterial
      genomes representing different genera and in eDNA of marine organisms, suggesting
      such modification as a widespread phenomenon. A coincidence between the Dnd
      phenotype and DNA modification by sulphur was demonstrated to occur in several
      representative bacterial genomes by the in vivo(35)S-labelling experiments.

PMID- 16102011
TI  - Positioning and the specific sequence of each 13-mer motif are critical for
      activity of the plasmid RK2 replication origin.
AB  - The minimal replication origin of the broad-host-range plasmid RK2, oriV,
      contains five iterons which are binding sites for the plasmid-encoded replication
      initiation protein TrfA, four DnaA boxes, which bind the host DnaA protein, and
      an AT-rich region containing four 13-mer sequences. In this study, 26 mutants
      with altered sequence and/or spacing of 13-mer motifs have been constructed and
      analysed for replication activity in vivo and in vitro. The data show that the
      replacement of oriV 13-mers by similar but not identical 13-mer sequences from
      Escherichia coli oriC inactivates the origin. In addition, interchanging the
      positions of the oriV 13-mers results in greatly reduced activity. Mutants with
      T/A substitutions are also inactive. Furthermore, introduction of single
      nucleotide substitutions demonstrates very restricted sequence requirements
      depending on the 13-mer position. Only two of the mutants are host specific,
      functional in Pseudomonas aeruginosa but not in E. coli. Our experiments
      demonstrate considerable complexity in the plasmid AT-rich region architecture
      required for functionality. It is evident that low internal stability of this
      region is not the only feature contributing to origin activity. Our studies
      suggest a requirement for sequence-specific protein interactions within the 13
      mers during assembly of replication complexes at the plasmid origin.

PMID- 16102012
TI  - YaeT (Omp85) affects the assembly of lipid-dependent and lipid-independent outer
      membrane proteins of Escherichia coli.
AB  - The Omp85 family of proteins has been found in all Gram-negative bacteria and
      even several eukaryotic organisms. The previously uncharacterized Escherichia
      coli member of this family is YaeT. The results of this study, consistent with
      previous Omp85 studies, show that the yaeT gene encodes for an essential cellular
      function. Direct examinations of the outer membrane fraction and protein assembly
      revealed that cells depleted for YaeT are severely defective in the biogenesis of
      outer membrane proteins (OMPs). Interestingly, assemblies of the two distinct
      groups of OMPs that follow either SurA- and lipopolysaccharide-dependent (OmpF/C)
      or -independent (TolC) folding pathways were affected, suggesting that YaeT may
      act as a general OMP assembly factor. Depletion of cells for YaeT led to the
      accumulation of OMPs in the fraction enriched for periplasm, thus indicating that
      YaeT facilitates the insertion of soluble assembly intermediates from the
      periplasm to the outer membrane. Our data suggest that YaeT's role in the
      assembly of OMPs is not mediated through a role in lipid biogenesis, as debated
      for Omp85 in Neisseria, thus advocating a conserved OMP assembly function of
      Omp85 homologues.

PMID- 16102013
TI  - The 5' untranslated region-mediated enhancement of intracellular listeriolysin O
      production is required for Listeria monocytogenes pathogenicity.
AB  - Listeriolysin O (LLO) and ActA are essential virulence determinants for Listeria
      monocytogenes pathogenesis. Transcription of actA and hly, encoding LLO, is
      regulated by PrfA and increases dramatically during intracellular infection. The
      5' untranslated regions (5' UTRs) of actA and prfA have been shown to upregulate
      expression of their respective gene products. Here, we demonstrate that the hly
      5' UTR plays a critical role in regulating expression of LLO during intracellular
      infection. Deletion of the hly 5' UTR, while retaining the hly ribosome binding
      site, had a moderate effect on LLO production during growth in broth culture, yet
      resulted in a marked decrease in LLO levels during intracellular infection. The
      diminished level of LLO resulted in a significant defect in bacterial cell-to
      cell spread during intracellular infection and a 10-fold reduction in virulence
      during in vivo infection of mice. Insertion of the hly 5' UTR sequence between a
      heterologous promoter and reporter gene sequences indicated that the hly 5' UTR
      functions independent of PrfA-mediated transcription and can enhance expression
      of cis-associated genes through a mechanism that appears to act at both a post
      transcriptional and translational level. The ability of the hly 5' UTR to
      increase gene expression can be exploited to achieve PrfA-independent
      complementation of virulence genes and high-level expression of single copy
      heterologous genes in L. monocytogenes.

PMID- 16102014
TI  - Transcriptional regulation of the circadian clock operon kaiBC by upstream
      regions in cyanobacteria.
AB  - In the cyanobacterium, Synechococcus elongatus PCC 7942, the kaiBC operon is
      upregulated by the KaiA protein and downregulated by the KaiC protein to generate
      circadian oscillation. We investigated the regulation of kaiBC transcription. A
      primer extension and deletion analyses of the upstream region mapped the
      sufficient promoter region (SPR) to base pairs -55 to +1 (the transcription start
      site, TSS) and identified a constitutive negative regulatory region upstream of
      the SPR (base pairs -897 to -56) that extended into the coding sequence of kaiA.
      Base-pair substitution within the SPR identified a sequence from -52 to -28 that
      was the essential element for transcription. Most of the examined sequences drove
      rhythmic expression of a luxAB reporter that was similar to the expression driven
      by the kaiBC promoter (PkaiBC) and responded to the overexpression of kaiA or
      kaiC, even in a promoter activity range of 1-8000%. These results indicate that
      circadian feedback regulation by KaiA and KaiC is addressed to a global step
      preceding transcription driven by PkaiBC. However, increasing or decreasing the
      intrinsic activity of PkaiBC greatly affected the rhythm, suggesting that
      constitutive adjustment of PkaiBC activity by the sequences identified here is
      essential for the oscillator.

PMID- 16102015
TI  - A novel, conserved cluster of genes promotes symbiotic colonization and sigma
      dependent biofilm formation by Vibrio fischeri.
AB  - Vibrio fischeri is the exclusive symbiont residing in the light organ of the
      squid Euprymna scolopes. To understand the genetic requirements for this
      association, we searched a library of V. fischeri transposon insertion mutants
      for those that failed to colonize E. scolopes. We identified four mutants that
      exhibited severe defects in initiating colonization. Sequence analysis revealed
      that the strains contained insertions in four different members of a cluster of
      21 genes oriented in the same direction. The predicted gene products are similar
      to proteins involved in capsule, exopolysaccharide or lipopolysaccharide
      biosynthesis, including six putative glycosyltransferases. We constructed
      mutations in five additional genes and found that they also were required for
      symbiosis. Therefore, we have termed this region syp, for symbiosis
      polysaccharide. Homologous clusters also exist in Vibrio parahaemolyticus and
      Vibrio vulnificus, and thus these genes may represent a common mechanism for
      promoting bacteria-host interactions. Using lacZ reporter fusions, we observed
      that transcription of the syp genes did not occur under standard laboratory
      conditions, but could be induced by multicopy expression of sypG, which encodes a
      response regulator with a predicted sigma54 interaction domain. This induction
      depended on sigma54, as a mutation in rpoN abolished syp transcription. Primer
      extension analysis supported the use of putative sigma54 binding sites upstream
      of sypA, sypI and sypM as promoters. Finally, we found that multicopy expression
      of sypG resulted in robust biofilm formation. This work thus reveals a novel
      group of genes that V. fischeri controls through a sigma54-dependent response
      regulator and uses to promote symbiotic colonization.

PMID- 16102016
TI  - The Dif chemosensory pathway is directly involved in phosphatidylethanolamine
      sensory transduction in Myxococcus xanthus.
AB  - Myxococcus xanthus cells glide on solid surfaces and are chemotactically
      stimulated by certain phosphatidylethanolamine species. The dif gene cluster
      consists of six genes, difABCDEG, five of which encode proteins homologous to
      known chemotaxis proteins. DifA and DifE are required for the biosynthesis of
      fibrils, an extracellular matrix comprised of polysaccharide and protein.
      Chemotactic stimulation by 1,2-O-Bis[11-(Z)-hexadecenoyl]-sn-glycero-3
      phosphatidylethanolamine (16:1 PE) and dilauroyl PE (12:0 PE) requires fibrils.
      Although previous work has shown that difA and difE mutants are not stimulated by
      12:0 PE, these results do not distinguish between a dependence on fibrils or a
      direct role in chemosensory transduction. Here we provide evidence that the Dif
      chemosensory pathway directly mediates PE sensory transduction. First,
      stimulation by and adaptation to 16:1 PE requires all of the dif genes, including
      difBDG, which are not essential for fibril biogenesis. Second, a specific residue
      within the first putative methylation domain of DifA is required for stimulation
      by 16:1 PE but not fibril biogenesis. Transmembrane signalling through a chimeric
      NarX-DifA chemoreceptor is required for fibril formation but not for stimulation
      by or adaptation to 16:1 PE. Third, difD and difE are required for stimulation by
      dioleoyl PE (18:1 PE) although the response does not require fibrils. Taken
      together these results argue that the Dif pathway mediates both matrix formation
      and lipid chemotaxis.

PMID- 16102019
TI  - Treatment of venous thromboembolism.
AB  - This review on the treatment of patients with venous thromboembolic disease
      consists of three sections. The first section describes the epidemiology, natural
      history and reasons for treatment of venous thromboembolism (VTE), as well as a
      short overview on the evaluation of the use of antithrombotic agents and the
      spectrum of treatment options. In the second section, the evidence from clinical
      studies available to us in 2005 with the various treatment modalities is
      summarized. This section describes the current recommendations about how to treat
      patients with VTE initially and long term. Finally, in the third section the
      challenges for the treatment of patients beyond 2005 are discussed.

PMID- 16102020
TI  - Identifying novel genetic determinants of hemostatic balance.
AB  - Incomplete penetrance and variable expressivity confound the diagnosis and
      therapy of most inherited thrombotic and hemorrhagic disorders. For many of these
      diseases, some or most of this variability is determined by genetic modifiers
      distinct from the primary disease gene itself. Clues toward identifying such
      modifier genes may come from studying rare Mendelian disorders of hemostasis.
      Examples include identification of the cause of combined factor V and VIII
      deficiency as mutations in the ER Golgi intermediate compartment proteins LMAN1
      and MCFD2. These proteins form a cargo receptor that facilitates the transport of
      factors V and VIII, and presumably other proteins, from the ER to the Golgi. A
      similar positional cloning approach identified ADAMTS-13 as the gene responsible
      for familial TTP. Along with the work of many other groups, these findings
      identified VWF proteolysis by ADAMTS-13 as a key regulatory pathway for
      hemostasis. Recent advances in mouse genetics also provide powerful tools for the
      identification of novel genes contributing to hemostatic balance. Genetic studies
      of inbred mouse lines with unusually high and unusually low plasma VWF levels
      identified polymorphic variation in the expression of a glycosyltransferase gene,
      Galgt2, as an important determinant of plasma VWF levels in the mouse. Ongoing
      studies in mice genetically engineered to carry the factor V Leiden mutation may
      similarly identify novel genes contributing to thrombosis risk in humans.

PMID- 16102021
TI  - Significance of the transcription factor KLF5 in cardiovascular remodeling.
AB  - Structural remodeling of the heart and blood vessels is an important pathologic
      process in the development of many cardiovascular diseases. However,
      transcriptional regulation of altered gene expression during cardiovascular
      remodeling is not well understood. We previously isolated KLF5/basic
      transcription element-binding (BTEB)2, a Kruppel-like factor, as a transcription
      factor that binds the promoter of the embryonic smooth muscle myosin heavy chain
      gene (SMemb). KLF5 activates many genes inducible during cardiovascular
      remodeling, such as platelet-derived growth factor (PDGF)-A/B, Egr-1, plasminogen
      activator inhibitor-1 (PAI-1), inducible nitric oxide synthase (iNOS), and
      vascular endothelial growth factor (VEGF) receptors. KLF5 is abundantly expressed
      in embryonic smooth muscles and is down-regulated with vascular development, but
      reinduced in proliferative neointimal smooth muscles in response to vascular
      injury. In KLF5 gene-targeted mice, homozygotes die at an early embryonic stage
      whereas heterozygotes are apparently normal. However, in response to external
      stress, arteries of heterozygotes exhibit diminished levels of smooth muscle and
      adventitial cell activation. Furthermore, angiotensin II-induced cardiac
      hypertrophy and fibrosis are attenuated in heterozygotes. KLF5 activities are
      regulated by many transcriptional regulators and nuclear receptors, such as
      retinoic acid receptor-alpha (RAR alpha), NF-kappaB, PPAR gamma, p300, and SET.
      Interestingly, RAR alpha agonist suppresses KLF5 and cardiovascular remodeling,
      whereas RAR alpha antagonist activates KLF5 and induces angiogenesis. These
      results indicate that KLF5 is an essential transcription factor in cardiovascular
      remodeling and a potential therapeutic target for cardiovascular disease.

PMID- 16102022
TI  - Therapeutic approaches in arterial thrombosis.
AB  - The current standard of care for the treatment of arterial thrombosis includes
      anticoagulants and three classes of antiplatelet agents--aspirin, thienopyridines
      and glycoprotein IIb-IIIa antagonists. Although these drugs have had a
      significant impact on morbidity and mortality in several patient populations, up
      to 15% of the high risk patients with acute coronary syndrome continue to suffer
      from ischemic events. This problem may occur, in part, because the platelets in
      many patients are non-responsive to aspirin and clopidogrel. Murine models now
      indicate that platelets are not only responsible for arterial occlusion, they are
      also involved in the progression of atherosclerotic disease. New opportunities
      have emerged identifying potential targets and strategies for drug discovery
      suited to address these deficiencies by more effectively modulating platelet
      adhesion, thrombus growth, thrombus stability and the pro-inflammatory activity
      of platelets. In addition, a growing need has emerged for the development of
      bedside devices capable of bringing personalized medicine to patients being
      treated with antithrombotic drugs in order to measure the pharmacodynamic
      activities of new therapies, to assess the activities achieved by combined
      antithrombotic therapy, and to identify patients that fail to respond.

PMID- 16102023
TI  - The P-selectin, tissue factor, coagulation triad.
AB  - The primary importance of tissue factor (TF) in blood coagulation and thrombus
      propagation has been recognized for many years. Nevertheless, our view about the
      origin of TF activity, necessary for normal hemostasis and found in pathologic
      conditions, needs to be revised in the light of recent observations. Pioneering
      work by Yale Nemerson's group showed that circulating TF on microparticles (MPs),
      could promote thrombus growth. The origin and characteristics of this 'blood
      borne' TF are targets of intense research as well as intense debate. Surprising
      observations now implicate the adhesion receptor P-selectin (P-sel), known for
      its role in inflammation, in these MPs' generation. P-sel, translocated from
      granules to the cell surfaces of activated platelets and endothelial cells, was
      recently found to play multiple roles in hemostasis. Expressed on endothelium, it
      can mediate platelet rolling. Signaling by P-sel through its receptor on
      leukocytes, P-selectin glycoprotein ligand 1 (PSGL-1), induces the generation of
      TF-positive, highly procoagulant MPs. In addition, P-sel on activated platelets
      helps to recruit these MPs specifically to thrombi. In this review, we discuss
      the roles of P-sel and TF-positive MPs and highlight strategies to modulate
      hemostasis by modulating the P-sel, TF, coagulation triad.

PMID- 16102024
TI  - Determinants of the interindividual variability in response to antiplatelet
      drugs.
AB  - The aim of this review article is to discuss the main determinants of the
      interindividual variability in response to antiplatelet agents. The main sources
      of pharmacokinetic and pharmacodynamic variability are reviewed, with particular
      emphasis on aspirin and clopidogrel. The term 'resistance' is uninformative of
      the mechanism(s) underlying interindividual variability in response to these
      antiplatelet agents, and is potentially misleading. Increased awareness of the
      distinct factors potentially interfering with the desired antiplatelet effects of
      aspirin or clopidogrel, particularly avoidable drug interactions, may ultimately
      result in better patient management than requesting unnecessary costly tests of
      platelet function. Similarly, new studies addressing the interindividual
      variability in response to these antiplatelet agents should rely upon mechanism
      based biochemical end-points rather than platelet aggregation measurements. As
      with any drug used to prevent atherothrombosis, treatment 'failure' can occur
      with aspirin or clopidogrel perhaps not surprisingly, given the multifactorial
      nature of atherothrombosis. There is no scientific basis for changing
      antiplatelet therapy in the face of a treatment 'failure', as we cannot be sure
      whether a second vascular event occurring in the same patient will reflect the
      same pathophysiological event that led to the first. Moreover, we have no
      controlled evidence that changing therapy is a more effective strategy than
      maintaining an evidence-based therapy.

PMID- 16102025
TI  - Thrombophilia and pregnancy outcomes.
AB  - Pregnancy complications are still a challenge for physicians, because knowledge
      of pathomechanisms and prophylactic measures is still limited. In recent years
      thrombophilia as a risk factor for pregnancy complications has gained much
      attention in the scientific community. However, data on this topic in the
      literature are conflicting. Besides an established association between
      antiphospholipid antibodies and pregnancy loss, available data suggest additional
      associations for antithrombin deficiency, hyperhomocysteinemia and also for
      factor (F)V Leiden, prothrombin G20210A variation, and protein S-deficiency. The
      contribution of thrombophilia to the risk of pre-eclampsia is less well
      established and recent studies did not confirm earlier data suggesting an
      association between thrombophilia and pre-eclampsia. A limited number of
      prospective studies have failed to reveal an increased risk of pregnancy
      complications in unselected women with thrombosis risk factors. Low-molecular
      weight heparin (LMWH) seems to have a positive effect on pregnancy outcome after
      single or recurrent abortions, however, data from only one controlled trial are
      available. Experience in the prevention of pre-eclampsia by prophylactic heparin
      is very limited, and in addition, data on pregnancy complications in women with
      known heritable thrombophilia or a history of thrombosis are inconsistent. These
      women will usually have a favorable pregnancy outcome referring to the European
      Prospective Cohort on Thrombophilia Study. In conclusion, thrombophilia screening
      might be justified in women with pregnancy loss and treatment with LMWH might be
      considered in those with pregnancy loss and thrombophilia. Further prospective
      studies and controlled interventional trials are urgently needed.

PMID- 16102026
TI  - Venous thromboembolism: disease burden, outcomes and risk factors.
AB  - The epidemiology of venous thromboembolism (VTE) in the community has important
      implications for VTE prevention and management. This review describes the disease
      burden (incidence), outcomes (survival, recurrence and complications) and risk
      factors for deep vein thrombosis and pulmonary embolism occurring in the
      community. Recent comprehensive studies of the epidemiology of VTE that reported
      the racial demography and included the full spectrum of disease occurring within
      a well-defined geographic area over time, separated by event type, incident vs.
      recurrent event and level of diagnostic certainty, were reviewed. Studies of VTE
      outcomes had to include a relevant duration of follow-up. VTE incidence among
      whites of European origin exceeded 1 per 1000; the incidence among persons of
      African and Asian origin may be higher and lower, respectively. VTE incidence
      over recent time remains unchanged. Survival after VTE is worse than expected,
      especially for pulmonary embolism. Thirty percent of patients develop VTE
      recurrence and venous stasis syndrome. Exposures can identify populations at risk
      but have a low predictive value for the individual. An acquired or familial
      thrombophilia may predict the subset of exposed persons who actually develop
      symptomatic VTE. In conclusion, VTE is a common, lethal disease that recurs
      frequently and causes serious long-term complications. To improve survival and
      prevent complications, VTE occurrence must be reduced. Better individual risk
      stratification is needed in order to modify exposures and target primary and
      secondary prophylaxis to the person who would benefit most.

PMID- 16102027
TI  - Circulating inflammatory markers and risks of cardiovascular and non
      cardiovascular disease.
AB  - There is current interest in the associations of circulating inflammatory markers
      (C-reactive protein, fibrinogen, white cell count, albumin, erythrocyte
      sedimentation rate, the factor VIII:von Willebrand factor complex, the tissue
      plasminogen activator:plasminogen activator inhibitor type 1 complex, fibrin D
      dimer) not only with prognosis in acute coronary syndromes and acute stroke, but
      also in prediction of cardiovascular events in the general population. Recent
      meta-analyses of long-term prospective studies have established their
      associations with coronary heart disease (CHD) events, which may be cause,
      consequence or coincidence. These markers are also associated in epidemiologic
      studies of general populations with many cardiovascular risk factors (which may
      confound their associations with CHD risk), and also with asymptomatic arterial
      disease (of which they be consequences: 'reverse causality'). The causality of
      their associations with cardiovascular events is questioned by their lack of
      specificity for risk of cardiovascular events; and by the lack of association of
      their functional genotypes with CHD in 'Mendelian randomized trials'. Hence,
      proof of causality awaits testing in randomized-controlled trials of long-term
      selective reduction by future agents. Markers are of little additional predictive
      value to current cardiovascular risk scores, and it is premature to advocate
      their use in screening for cardiovascular risk prior to careful evaluation of
      costs, risks, and benefits.

PMID- 16102028
TI  - Medical management of peripheral arterial disease.
AB  - Whether symptomatic or not, peripheral arterial disease (PAD), atherosclerosis in
      the arteries of the lower extremities, is a common disorder in the general
      population. The prevalence increases with age and under the influence of vascular
      risk factors. The most classic symptomatic expression of PAD is intermittent
      claudication. However, the majority of patients with PAD is asymptomatic or has
      leg symptoms other than classic intermittent claudication. Both symptomatic and
      asymptomatic subjects with PAD have increased mortality rates, mainly due to
      cardiovascular and cerebrovascular expressions of atherosclerotic disease. This
      review focuses on the current available medical therapies for PAD, including risk
      factor modification and antiplatelet therapies, as well as strategies for
      symptomatic relief in both patients with intermittent claudication and patients
      with critical limb ischemia. In general, risk factor modification and
      antiplatelet therapy is essential in all patients with PAD to prevent systemic
      atherosclerotic complications. Furthermore, for symptomatic relief exercise
      therapy is the main intervention while pharmacological treatment should be only
      complementary. In patients with critical limb ischemia, when revascularization
      therapy is not possible, an attempt should be made to avoid amputation with
      conservative treatment using analgesics, vasodilators and/or anticoagulants. In
      case of an acute onset of critical limb ischemia, thrombolysis is indicated.

PMID- 16102029
TI  - Preventable stroke and stroke prevention.
AB  - Stroke is a major cause of death and disability in the world. The main causes of
      stroke are atherothromboembolism and cardiogenic embolism. The main causal and
      treatable risk factors for atherothromboembolic ischemic stroke are increasing
      blood pressure (BP), increasing cholesterol, cigarette smoking and diabetes; and
      the main risk factors for cardiogenic ischemic stroke are atrial fibrillation
      (AF) and ischemic heart disease. Strategies to reduce the incidence of stroke
      include prevention of first-ever and recurrent stroke, and treatment of patients
      with acute stroke to reduce death and disability. The two main strategies of
      stroke prevention are the 'population' (or 'mass') approach and the 'high risk'
      approach. The 'population' approach aims to reduce stroke by lowering the
      prevalence and mean level of causal risk factors in the community, by means of
      public education and government legislation. The 'high risk' approach aims to
      reduce stroke by identifying individuals at high risk of stroke, and lowering
      their risk by means of optimal medical therapies. Level 1 evidence from
      randomized controlled trials indicates that effective treatments for high risk
      patients include control of causal risk factors (lowering BP, lowering blood
      cholesterol), antithrombotic therapy (antiplatelet therapy with aspirin,
      clopidogrel, or the combination of aspirin and dipyridamole for patients in sinus
      rhythm, and anticoagulation with warfarin or ximelagatran for patients in AF)
      and, where appropriate, carotid revascularization for patients with severe
      carotid stenosis.

PMID- 16102030
TI  - Mechanisms of homocysteine-induced atherothrombosis.
AB  - Elevation of plasma homocysteine level is a risk factor for cardiovascular
      disease, stroke, and venous thromboembolism. It is still uncertain, however,
      whether hyperhomocysteinemia is a causative factor or a marker of vascular
      disease. The strongest evidence that homocysteine plays a causal role in
      atherothrombosis has been provided by studies using animal models. In the past
      decade, considerable progress in defining the vascular effects of
      hyperhomocysteinemia was achieved through the use of genetic and dietary
      approaches to induce hyperhomocysteinemia in experimental animals. A key vascular
      phenotype observed in hyperhomocysteinemic animals is endothelial dysfunction,
      manifested by decreased bioavailability of endothelium-derived nitric oxide.
      Impairment of endothelial function may be mediated by either accelerated
      oxidative inactivation of nitric oxide or inhibition of nitric oxide production
      caused by the endogenous nitric oxide synthase inhibitor, asymmetric
      dimethylarginine. Hyperhomocysteinemia also increases susceptibility to arterial
      thrombosis and accelerates the development of atherosclerosis in susceptible
      models such as the apolipoprotein E-deficient mouse. Mechanisms of
      atherothrombosis may include homocysteine-induced thiolation or acylation of
      plasma or endothelial proteins and endoplasmic reticulum stress, which activates
      signal transduction pathways leading to inflammation and apoptosis.

PMID- 16102031
TI  - Aspirin resistance.
AB  - Treatment failures occur with any drug and aspirin is no exception. Evidence is
      growing to indicate that there are subpopulations that do not respond to
      antithrombotic action of aspirin. The term 'aspirin resistance' has been used to
      describe a number of different phenomena, including inability of aspirin to: (i)
      protect against cardiovascular events despite its regular intake; (ii) to affect
      various laboratory tests, reflecting platelet activity. Research on aspirin
      resistance yielded interesting results in clinical pharmacology and
      pharmacogenetics. Future studies will show whether genotyping for polymorphisms
      might be of value in everyday clinical use of aspirin. Present data indicate that
      in survivors of recent myocardial infarction or unstable angina, patients
      receiving coronary artery bypass grafts, as well as in subjects with
      hypercholesterolemia, aspirin resistance has to be considered when implementing
      antithrombotic therapy. However, in individual patients the available laboratory
      tests are of no particular use to predict reliably the clinical outcome or to
      guide in making therapeutic decision. Prospective clinical trials seem necessary
      to reach such conclusions.

PMID- 16102032
TI  - Thrombotic thrombocytopenic purpura.
AB  - This overview summarizes the history of thrombotic thrombocytopenic purpura (TTP)
      from its initial recognition in 1924 as a most often fatal disease to the
      discovery in 1997 of ADAMTS-13 deficiency as a major risk factor for acute
      disease manifestation. The cloning of the metalloprotease, ADAMTS-13, an
      essential regulator of the extremely adhesive unusually large von Willebrand
      factor (VWF) multimers secreted by endothelial cells, as well as ADAMTS-13
      structure and function are reviewed. The complex, initially devised assays for
      ADAMTS-13 activity and the possible limitations of static in vitro assays are
      described. A new, simple assay using a recombinant 73-amino acid VWF peptide as
      substrate will hopefully be useful. Hereditary TTP caused by homozygous or double
      heterozygous ADAMTS-13 mutations and the nature of the mutations so far
      identified are discussed. Recognition of this condition by clinicians is of
      utmost importance, because it can be easily treated and--if untreated--frequently
      results in death. Acquired TTP is often but not always associated with severe,
      autoantibody-mediated ADAMTS-13 deficiency. The pathogenesis of cases without
      severe deficiency of the VWF-cleaving protease remains unknown, affected patients
      cannot be distinguished clinically from those with severely decreased ADAMTS-13
      activity. Survivors of acute TTP, especially those with autoantibody-induced
      ADAMTS-13 deficiency, are at a high risk for relapse, as are patients with
      hereditary TTP. Patients with thrombotic microangiopathies (TMA) associated with
      hematopoietic stem cell transplantation, neo-plasia and several drugs, usually
      have normal or only moderately reduced ADAMTS-13 activity, with the exception of
      ticlopidine-induced TMA. Diarrhea-positive-hemolytic uremic syndrome (D+ HUS),
      mainly occurring in children is due to enterohemorrhagic Escherichia coli
      infection, and cases with atypical, D- HUS may be associated with factor H
      abnormalities. Treatment of acquired idiopathic TTP involves plasma exchange with
      fresh frozen plasma (FFP), and probably immunosuppression with corticosteroids is
      indicated. We believe that, at present, patients without severe acquired ADAMTS
      13 deficiency should be treated with plasma exchange as well, until better
      strategies become available. Constitutional TTP can be treated by simple FFP
      infusion that rapidly reverses acute disease and--given prophylactically every 2
      3 weeks--prevents relapses. There remains a large research agenda to improve
      diagnosis of TMA, gain further insight into the pathophysiology of the various
      TMA and to improve and possibly tailor the management of affected patients.

PMID- 16102033
TI  - Cellular immune responses in hemophilia: why do inhibitors develop in some, but
      not all hemophiliacs?
AB  - Advances in molecular immunology over the past two decades permit a better
      understanding of why antibodies develop to peptide antigens like factor VIII and
      the events that lead to the development of these antibodies. Two important
      variables that are critical in antibody formation are (i) the molecular defect in
      FVIII and the consequences of that defect on translation and protein production,
      and (ii) the major histocompatibility complex (MHC) molecules which bind specific
      peptide sequences and present those peptides to CD4 T lymphocytes to initiate the
      cellular cascade leading to B-cell stimulation and differentiation, and
      ultimately to antibody formation. Inhibitors develop in hemophilia because
      transfused FVIII can be seen as a foreign protein and elicits an immune response
      in much the same way that any other foreign protein might elicit an immune
      response. However, not all hemophiliacs generate an immune response, either
      because they do not recognize FVIII as foreign or because their MHC phenotype is
      such that a cellular immune response is not initiated. In this model, it is the
      combination of molecular defect and MHC phenotype that determines inhibitor
      formation. The interplay of these two variables in the context of why some but
      not all hemophiliacs develop antibodies after treatment with replacement factor
      is reviewed.

PMID- 16102034
TI  - Gene transfer for hemophilia: can therapeutic efficacy in large animals be safely
      translated to patients?
AB  - Gene transfer is a novel area of therapeutics in which the active agent is a
      nucleic acid rather than a protein or small molecule. As early as 1997,
      investigators reported long-term expression of therapeutic levels of factor IX
      using gene transfer techniques in hemophilia B mice, and similar data were
      thereafter reported in mice with hemophilia A. Efforts to translate these results
      to hemophilic dog models at first yielded only marginally therapeutic levels (1%
      2% normal circulating levels), but within the past few years have achieved levels
      in the range of 10%-20% through multiple different gene transfer strategies.
      Early phase clinical testing has revealed that many aspects of gene transfer in
      humans were accurately predicted by studies in hemophilic dogs, but that other
      aspects were not, and were only appreciated as a result of clinical testing.
      Studies in the next few years will determine whether the problems identified in
      preclinical and early phase clinical testing can be solved to develop a
      therapeutic gene transfer approach to hemophilia.

PMID- 16102035
TI  - The promise and challenges of bioengineered recombinant clotting factors.
AB  - The past 10 years of clinical experience have demonstrated the safety and
      efficacy of recombinant clotting factors. With the adoption of prophylactic
      strategies, there has been considerable progress in avoiding the complications of
      hemophilia. Now, insights from our understanding of clotting factor structure and
      function, mechanisms of hemophilia and inhibitors, gene therapy advances and a
      worldwide demand for clotting factor concentrates leave us on the brink of
      embracing targeted bioengineering strategies to further improve hemophilia
      therapeutics. The ability to bioengineer recombinant clotting factors with
      improved function holds promise to overcome some of the limitations in current
      treatment, the high costs of therapy and increase availability to a broader world
      hemophilia population. Most research has been directed at overcoming the inherent
      limitations of rFVIII expression and the inhibitor response. This includes
      techniques to improve rFVIII biosynthesis and secretion, functional activity,
      half-life and antigenicity/immunogenicity. Some of these proteins have already
      reached commercialization and have been utilized in gene therapy strategies,
      while others are being evaluated in pre-clinical studies. These novel proteins
      partnered with advances in gene transfer vector design and delivery may
      ultimately achieve persistent expression of FVIII leading to an effective long
      term treatment strategy for hemophilia A. In addition, these novel FVIII proteins
      could be partnered with new advances in alternative recombinant protein
      production in transgenic animals yielding an affordable, more abundant supply of
      rFVIII. Novel rFIX proteins are being considered for gene therapy strategies
      whereas novel rVIIa proteins are being evaluated to improve the potency and
      extend their plasma half-life. This review will summarize the status of current
      recombinant clotting factors and the development and challenges of recombinant
      clotting factors bioengineered for improved function.

PMID- 16102036
TI  - von Willebrand factor: two sides of a coin.
AB  - Everyone experiences minor bleeding and clotting, and many illnesses feature
      extremes of hemorrhage or thrombosis. Recent advances have illuminated the ways
      in which von Willebrand factor (VWF) contributes to both kinds of hemostatic
      emergency, whether mundane or life threatening, often through disturbances in VWF
      synthesis or catabolism. von Willebrand factor multimer assembly depends on the
      ability of the propeptide to promote disulfide bond formation in the Golgi,
      possibly by acting as a pH-sensitive oxidoreductase. Once secreted into the
      blood, multimers are subject to competing processes of clearance and of
      proteolysis by ADAMTS-13. Defects in the secretion or intravascular clearance of
      VWF can cause exceptionally severe forms of von Willebrand disease (VWD) type 1.
      Defects in the assembly of VWF multimers, or exaggerated proteolytic degradation
      by ADAMTS-13, can cause VWD type 2A and contribute to VWD type 2B. Conversely,
      defects in the feedback proteolysis of VWF by ADAMTS-13 can cause thrombotic
      thrombocytopenic purpura (TTP). The pathophysiologic importance of VWF is not
      limited to the dramatic phenotypes of VWD and TTP. In fact, VWF level also
      correlates with thrombosis risk and inversely with bleeding risk within the
      apparently healthy population. More research is needed to understand how VWF
      function is regulated, and to enable physicians to use this knowledge for the
      benefit of their patients.

PMID- 16102037
TI  - Cleavage of ultra-large von Willebrand factor by ADAMTS-13 under flow conditions.
AB  - von Willebrand factor (VWF) is a critical ligand for platelet adhesion and
      aggregation. It is synthesized and released as multimers composed of various
      numbers of monomers. When first released from the storage granules of endothelial
      cells, VWF multimers are rich in the ultra-large (UL) forms that spontaneously
      bind the GP Ib-IX complex and aggregate platelets. These prothrombotic ULVWF
      multimers are rapidly cleaved by the metalloprotease ADAMTS-13 (A Disintegrin and
      Metalloprotease with ThromboSpondin motif) to smaller and much less active forms.
      Recently, several methods have been developed to measure ADAMTS-13 activity in
      vitro and to link its deficiency to thrombotic thrombocytopenic purpura.
      Correlations between the structure and functions of the metalloprotease have also
      been extensively studied using recombinant technologies. However, questions
      remain regarding the proper substrate for the metalloprotease, the time and
      location of ULVWF proteolysis, and the role of fluid shear stress. In this brief
      review, we have discussed a potential model for ULVWF proteolysis by ADAMTS-13 in
      vivo. In this model, ULVWF is anchored to the surface of endothelial cells to
      form string-like structures under fluid shear stress. Such an elongated
      conformation facilitates ULVWF cleavage by exposing either the cleavage or
      binding sites for the metalloprotease. When ADAMTS-13 is deficient, the uncleaved
      ULVWF accumulates in plasma and on endothelial cells to capture platelets. This
      leads to platelet aggregation and thromboembolism. Dissecting the process of
      ULVWF proteolysis is important for not only understanding the pathophysiology of
      thrombotic microangiopathies, but also developing more effective means to treat
      these deadly diseases.

PMID- 16102038
TI  - Mechanisms of thrombopoiesis.
AB  - Megakaryocytes (MKs) expand and differentiate over several days in response to
      thrombopoietin (Tpo) before releasing innumerable blood platelets. The final
      steps in platelet assembly and release represent a unique cellular transformation
      that is orchestrated by a range of transcription factors, signaling molecules,
      and cytoskeletal elements. Here we review recent advances in the physiology and
      molecular basis of MK differentiation. Genome-wide approaches, including
      transcriptional profiling and proteomics, have been used to identify novel
      platelet products and differentiation markers. The extracellular factors, stromal
      derived factor (SDF)-1 chemokine and fibroblast growth factor (FGF)-4 direct MK
      interactions with the bone marrow stroma and regulate cytokine-independent cell
      maturation. An abundance of bone marrow MKs induce pathologic states, including
      excessive bone formation and myelofibrosis, and the basis for these effects is
      now better appreciated. We review the status of transcription factors that
      control MK differentiation, with special emphasis on nuclear factor-erythroid 2
      (NF-E2) and its two putative target genes, beta1-tubulin and 3-beta
      hydroxysteroid reductase. MKs express steroid receptors and some estrogen
      ligands, which may constitute an autocrine loop in formation of proplatelets, the
      cytoplasmic protrusions within which nascent blood platelets are assembled.
      Finally, we summarize our own studies on cellular and molecular facets of
      proplatelet formation and place the findings within the context of outstanding
      questions about mechanisms of thrombopoiesis.

PMID- 16102039
TI  - Platelets in atherothrombosis: lessons from mouse models.
AB  - Platelets play a central role in hemostasis and thrombosis but also in the
      initiation of atherosclerosis, making platelet receptors and their intracellular
      signaling pathways important molecular targets for antithrombotic and anti
      inflammatory therapy. Historically, much of the knowledge about hemostasis and
      thrombosis has been derived from patients suffering from bleeding and thrombotic
      disorders and the identification of the underlying molecular defects. In recent
      years, the availability of genetically modified mouse strains with defined
      defects in platelet function and the development of in vivo models to assess
      platelet-related physiologic and pathophysiologic processes have opened new ways
      to identify the individual roles and the interplay of platelet proteins in
      adhesion, activation, aggregation, secretion, and procoagulant activity in vitro
      and in vivo. This review will summarize key findings made by these approaches and
      discuss them in the context of human disease.

PMID- 16102040
TI  - Receptors, rafts, and microvesicles in thrombosis and inflammation.
AB  - Hemostasis at sites of blood vessel injury and its pathologic counterpart,
      thrombosis, involve a complex interplay between several blood elements: soluble
      proteins of the blood coagulation system, blood cells (most prominently
      platelets) and cell fragments, and elements of the vessel wall (endothelial cells
      and, at sites of injury, the exposed matrix and deeper cellular components). In
      this review, we focus on ways in which specialized membrane microdomains known as
      lipid rafts are involved in various phases of hemostasis and thrombosis.

PMID- 16102041
TI  - Platelet GPIb-IX-V-dependent signaling.
AB  - Although the signaling pathways related to GPIb-IX-V have not been fully
      elucidated, an accumulating body of evidence suggests that phospholipase C
      (PLC)gamma2 activation, subsequent Ca++ release and oscillations constitute an
      essential signal transduction pathway related to GPIb-IX-V. Src family kinases
      are required for PLCgamma2 activation, while FcR gamma-chain/Fc gammaRIIA may be
      dispensable for PLCgamma2 activation. Although PI-3K serves to potentiate various
      signaling events culminating in alpha(IIb)beta3 activation, PI-3K activity may be
      dispensable for Src-PLCgamma2 activation in GPIb-IX-V-mediated signaling.
      Glycosphingolipid-enriched microdomains (GEMs) appear to provide platforms for
      the signal transduction pathway related to GIb-IX-V, as the interaction between
      GPIb-IX-V and Src or PLCgamma2 tyrosine phosphorylation occurs exclusively in
      GEMs.

PMID- 16102042
TI  - GPVI and integrin alphaIIb beta3 signaling in platelets.
AB  - This review summarizes recent developments in our understanding of the molecular
      basis of platelet activation by two distinct types of surface receptor, the
      immunoglobulin GPVI, and the integrin alphaIIb beta3 (also known as GPIIbIIIa).
      These two classes of receptor signal through similar yet distinct tyrosine kinase
      based signaling cascades leading to activation of phospholipase C gamma2. The
      significance of these signaling cascades in platelet adhesion and platelet
      aggregation at arterial rates of shear is discussed.

PMID- 16102043
TI  - Autoimmune thrombocytopenia.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which
      platelets coated with mainly antibodies against platelet GPIIb/IIIa and GPIb/IX
      are destroyed in the spleen. Recent evidence suggests that platelets are also
      destroyed by cytotoxic T cells. The diagnosis is made by exclusion for other
      causes of thrombocytopenia. As routine blood counts are becoming more available,
      many mild cases of ITP (platelets >30 x 10(9) L(-1)) are being diagnosed and they
      usually do not require treatment. In patients with platelet counts persistently
      <30 x 10(9) L(-1), treatment with corticosteroids, and/or intravenous
      immunoglobulin (IVIG) or anti-D may be required. The primary goal of treatment is
      to maintain the platelet count at a safe level with minimal side effects. After 3
      6 months, if spontaneous remission has not occurred and if the side effects are
      significant, splenectomy is recommended. This is the single most effective
      treatment of ITP. The refractory patients who fails splenectomy and subsequently
      first- and second-line therapies, is a management dilemma. Therapeutic options
      are limited, available treatments potentially toxic and the chances of sustained
      response low. Observation with no active treatment is a reasonable option. With
      the increased availability of the thrombopoietic agents in the future, there may
      be a good prospect of keeping the platelet counts of these refractory patients at
      a safe long-term level with one of these drugs.

PMID- 16102044
TI  - Qualitative disorders of platelets and megakaryocytes.
AB  - Qualitative disorders of platelet function and production form a large group of
      rare diseases which cover a multitude of genetic defects that by and large have
      as a common symptom, excessive mucocutaneous bleeding. Glanzmann thrombasthenia,
      is enabling us to learn much about the pathophysiology of integrins and of how
      alphaIIb beta3 functions. Bernard-Soulier syndrome, an example of
      macrothrombocytopenia, combines the production of large platelets with a deficit
      or non-functioning of the major adhesion receptor of platelets, the GPIb-IX-V
      complex. Amino acid substitutions in GPIb alpha, may lead to up-regulation and
      spontaneous binding of von Willebrand factor as in Platelet-type von Willebrand
      disease. In disorders with defects in the MYH9 gene, macrothrombocytopenias are
      linked to modifications in kidney, eye or ear, whereas other inherited
      thrombocytopenias variously link a low platelet count with a propensity to
      leukemia, skeletal defects, learning impairment, and abnormal red cells. Defects
      of secretion from platelets include an abnormal alpha-granule formation as in the
      gray platelet syndrome (with marrow myelofibrosis), and of organelle biogenesis
      in the Hermansky-Pudlak and Chediak-Higashi syndromes where platelet dense body
      defects are linked to abnormalities of other lysosomal-like organelles including
      melanosomes. Finally, defects involving surface receptors (P2Y(12), TPalpha) for
      activating stimuli, of proteins essential for signaling pathways (including
      Wiskott-Aldrich syndrome), and of platelet-derived procoagulant activity (Scott
      syndrome) show how studies on platelet disorders are helping unravel the pathways
      of primary hemostasis.

PMID- 16102045
TI  - Integrin activation by talin.
AB  - The development and integrity of the cardiovascular system depends on integrins,
      a family of adhesion receptors, vitally important for homeostasis of animal
      species from fruit fly to man. Integrins are critical players in cell migration,
      cell adhesion, cell cycle progression, differentiation, and apoptosis.
      Consequently, integrins have a major impact on the patterning and functions of
      the blood and cardiovascular system. Integrins undergo conformational changes,
      which alter their affinity for ligands through a process operationally defined as
      integrin activation. Integrin activation is important for platelet aggregation,
      leukocyte extravasation, and cell adhesion and migration, thus influencing such
      processes as hemostasis, inflammation and angiogenesis. Recently, a series of
      studies have begun to define the mechanism of integrin activation by
      demonstrating that binding of a cytoskeletal protein, talin, to integrin beta
      subunit cytoplasmic tail is a last common step in integrin activation. These
      findings indicate that talin is likely to be at the center of converging
      signaling pathways regulating integrin activation.

PMID- 16102046
TI  - Snake venoms and hemostasis.
AB  - Snake venoms are complex mixtures of biologically active proteins and peptides.
      Many of them affect hemostasis by activating or inhibiting coagulant factors or
      platelets, or by disrupting endothelium. Based on sequence, these snake venom
      components have been classified into various families, such as serine proteases,
      metalloproteinases, C-type lectins, disintegrins and phospholipases. The various
      members of a particular family act selectively on different blood coagulation
      factors, blood cells or tissues. For almost every factor involved in coagulation
      or fibrinolysis there is a venom protein that can activate or inactivate it.
      Venom proteins affect platelet function by binding or degrading vWF or platelet
      receptors, activating protease-activated receptors or modulating ADP release and
      thromboxane A2 formation. Some venom enzymes cleave key basement membrane
      components and directly affect capillary blood vessels to cause hemorrhaging. L
      Amino acid oxidases activate platelets via H2O2 production.

PMID- 16102047
TI  - Protease-activated receptors in hemostasis, thrombosis and vascular biology.
AB  - The coagulation cascade and protease-activated receptors (PARs) together provide
      an elegant mechanism that links mechanical information in the form of tissue
      injury to cellular responses. These receptors appear to largely account for the
      cellular effects of thrombin and can mediate signaling to other trypsin-like
      proteases. An important role for PARs in hemostasis and thrombosis is established
      in animal models, and studies in knockout mice and nonhuman primates raise the
      question of whether PAR inhibition might offer an appealing new approach to the
      prevention and treatment of thrombosis. PARs may also trigger inflammatory
      responses to tissue injury. For example, PAR activation on endothelial cells and
      perhaps sensory afferents can trigger local accumulation of leukocytes and
      platelets and transudation of plasma. However, panoply of signaling systems and
      cell types orchestrates inflammatory responses, and efforts to define the
      relative importance and roles of PARs in various inflammatory processes are just
      beginning. Lastly, roles for PARs in blood vessel formation and other processes
      during embryonic development are emerging, and whether these reflect new roles
      for the coagulation cascade and/or PAR signaling to other proteases remains to be
      explored.

PMID- 16102048
TI  - The role of endothelial cell apoptosis in inflammatory and immune diseases.
AB  - The integrity of the endothelial lining of the vasculature is essential for
      vascular homeostasis and normal organ function. Endothelial injury or dysfunction
      has been implicated in the pathogenesis of diverse vascular diseases. Studies in
      vitro have demonstrated that a wide variety of stimuli can induce programmed cell
      death (apoptosis) of endothelial cells, and have suggested that apoptosis could
      be an important mechanism of vascular injury, resulting in vascular leak,
      inflammation, and coagulation. In this review, we focus on the potential role of
      endothelial apoptosis in the initiation and progression of inflammatory and
      immune disorders, reviewing human diseases and in vivo models in which
      endothelial cell apoptosis has been demonstrated. Although endothelial cell
      apoptosis is observed in many inflammatory and immune disorders, we find that
      there is, as yet, only limited experimental evidence demonstrating that it is
      critical to the pathogenesis of disease.

PMID- 16102049
TI  - New insights on oxidative stress in the artery wall.
AB  - Atherosclerosis and its resultant cardiovascular events represent a state of
      heightened oxidative stress that is commonly thought to contribute to
      atherogenesis. The aim of this review is to summarize the data linking oxidative
      events to the pathogenesis of atherosclerosis. Despite abundant data supporting
      the presence of lipid and protein oxidation in the vascular wall, the poor
      performance of antioxidant strategies in limiting either atherosclerosis or
      cardiovascular events from atherosclerosis remain a fundamental problem for
      implicating oxidative stress as pathophysiologically important. Direct evidence
      that oxidative stress in general, and the oxidative modification of low-density
      lipoprotein in particular, is both necessary and sufficient for atherosclerosis
      has been difficult to find. There are many potential reasons for this difficulty,
      not the least of which is our lack of sufficient knowledge delineating the
      precise molecular events that beget oxidative stress in the vessel wall, and the
      precise mediators involved. Further investigation elucidating these oxidative
      events are required to provide us with the tools to limit oxidative stress at its
      source and ameliorate all of its secondary phenomena. Only then will we know what
      components of atherosclerosis are directly due to oxidative stress.

PMID- 16102050
TI  - Angiogenesis: update 2005.
AB  - Angiogenesis has critical roles in normal vascular development and in important
      pathologies including cancer, wound healing and inflammation. This brief article
      will review the angiogenic response induced by the vascular permeability
      factor/vascular endothelial growth factor (VPF/VEGF) family of proteins and
      particularly VEGF-A, thought to be the single most important angiogenic factor.
      It will also review the steps and mechanisms by which VEGF-A induces the
      formation of new blood vessels and will provide an initial classification of the
      abnormal blood vessels that form in pathological angiogenesis. Finally, it will
      touch on the exciting relationships that are emerging between angiogenesis and
      the hemostatic and nervous systems.

PMID- 16102051
TI  - New anticoagulants.
AB  - The limitations of heparin and warfarin have prompted the development of new
      anticoagulant drugs for prevention and treatment of venous and arterial
      thromboembolism. Novel parenteral agents include synthetic analogs of the
      pentasaccharide sequence of heparin that mediates its interaction with
      antithrombin. Fondaparinux, the first synthetic pentasaccharide, is licensed for
      prevention of venous thromboembolism (VTE) after major orthopedic surgery and for
      initial treatment of patients with VTE. Idraparinux, a long-acting
      pentasaccharide that is administered subcutaneously once-weekly, is being
      compared with warfarin for treatment of VTE and for prevention of cardioembolic
      events in patients with atrial fibrillation. New oral anticoagulants include
      direct inhibitors of thrombin, factor Xa and factor IXa. Designed to provide more
      streamlined anticoagulation than warfarin, these agents can be given without
      routine coagulation monitoring. Ximelagatran, the first oral direct thrombin
      inhibitor, is as effective and safe as warfarin for prevention of cardioembolic
      events in patients with atrial fibrillation. However, ximelagatran produces a
      three-fold elevation in alanine transaminase levels in 7.9% of patients treated
      for more than a month, the long-term significance of which is uncertain. Whether
      other direct thrombin inhibitors or inhibitors of factors Xa or IXa also have
      this problem is under investigation. After a brief review of coagulation
      pathways, this paper focuses on new anticoagulants in advanced stages of clinical
      testing.

PMID- 16102052
TI  - Pathophysiology of the antiphospholipid syndrome.
AB  - Antiphospholipid syndrome is a distinct disorder with the clinical features of
      recurrent thrombosis in the venous or arterial circulation and fetal losses. Its
      serological marker is the presence of antiphospholipid antibodies in the blood of
      these patients. The relation between the presence of antibodies against anionic
      phospholipids and thromboembolic complications is well established over the last
      25 years but the pathophysiology of the syndrome is largely unclear. Even after
      all these years, there is a persisting debate about the specificity and
      sensitivity of the assays for the detection of antiphospholipid antibodies. We
      now accept that antibodies to beta2-glycoprotein I rather than to anionic
      phospholipids are the major pathological antibodies, although there is no clear
      consensus on how the presence of these antibodies correlates with the different
      clinical manifestations of the syndrome. In this review, we discuss the current
      methods of detection of the antibodies and our insight into the pathobiology of
      the syndrome. We propose a mechanism for describing how the presence of anti
      beta2-glycoprotein I antibodies relates to the different clinical manifestations
      observed.

PMID- 16102053
TI  - Molecular recognition mechanisms of thrombin.
AB  - Thrombin is the final protease generated in the blood coagulation cascade, and is
      the only factor capable of cleaving fibrinogen to create a fibrin clot. Unlike
      every other coagulation protease, thrombin is composed solely of its serine
      protease domain, so that once formed it can diffuse freely to encounter a large
      number of potential substrates. Thus thrombin serves many functions in hemostasis
      through the specific cleavage of at least a dozen substrates. The solution of the
      crystal structure of thrombin some 15 years ago revealed a deep active site cleft
      and two adjacent basic exosites, and it was clear that thrombin must utilize
      these unique features in recognizing its substrates. Just how this occurs is
      still being investigated, but recent data from thrombin mutant libraries and
      crystal structures combine to paint the clearest picture to date of the molecular
      determinants of substrate recognition by thrombin. In almost all cases, both
      thrombin exosites are involved, either through direct interaction with the
      substrate protein or through indirect interaction with a third cofactor molecule.
      The purpose of this article is to summarize recent biochemical and structural
      data in order to provide insight into the thrombin molecular recognition events
      at the heart of hemostasis.

PMID- 16102054
TI  - The vitamin K cycle.
AB  - Post-translational modification of glutamate to gamma carboxyl glutamate is
      required for the activity of vitamin K-dependent proteins. Carboxylation is
      accomplished by the enzyme gamma glutamyl carboxylase (GGCX) which requires the
      propeptide-containing substrate and three co-substrates: reduced vitamin K, CO2,
      and O2. Most propeptides bind tightly to GGCX and all of the Glu residues that
      will be modified are modified during one binding event. Complete carboxylation is
      thus dependent upon the rate of carboxylation and the dissociation rate constant
      of the substrate from the GGCX enzyme. If the propeptide is released before
      carboxylation is complete, partially carboxylated vitamin K-dependent proteins
      are produced. The rate of carboxylation is mainly controlled by the level of
      reduced vitamin K available for the reactions while the dissociation rate
      constant is dependent upon both the propeptide and the Gla domain of the
      substrate. In addition, there are allosteric effects that increase the rate of
      dissociation of the fully carboxylated substrates. Carboxylation requires the
      abstraction of a proton from the 4-carbon of glutamate by reduced vitamin K and
      results in the conversion of vitamin K to vitamin K epoxide. The vitamin K
      epoxide must be recycled to vitamin K before it can be reused, a reaction
      catalyzed by the enzyme vitamin K epoxide reductase (VKOR). The gene for VKOR has
      recently been identified but the enzyme itself has not been purified to
      homogeneity. It appears, however, that most of the variability observed in
      patients response to warfarin may be attributed to variability in the VKOR gene.

PMID- 16102055
TI  - PAI-1 and atherothrombosis.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is the major physiologic inhibitor of
      tissue-type plasminogen activator in plasma, and is elevated in a variety of
      clinical situations that are associated with increased risk of ischemic
      cardiovascular events. Recent insights into the biology of PAI-1 suggest that it
      is more than just an innocent bystander in the pathogenesis of ischemic heart
      disease. Elevated PAI-1 levels appear to increase the risk of atherothrombotic
      events and may also promote the progression of vascular disease. The development
      and testing of specific PAI-1 antagonists will enable basic and clinical
      investigators the opportunity to test the hypothesis that vascular PAI-1 excess
      promotes the development of intravascular thrombosis and atherosclerosis.

PMID- 16102056
TI  - Beyond endocytosis: LRP function in cell migration, proliferation and vascular
      permeability.
AB  - The low-density lipoprotein (LDL) receptor related protein (LRP1 or LRP) is a
      large endocytic receptor widely expressed in several tissues and known to play
      roles in areas as diverse as lipoprotein metabolism, degradation of proteases,
      activation of lysosomal enzymes and cellular entry of bacterial toxins and
      viruses. This member of the LDL receptor superfamily is constitutively
      endocytosed from the membrane and recycled back to the cell surface. Its many
      functions were long thought to involve its ability to bind over 30 different
      ligands and deliver them to lysosomes for degradation. However, LRP has since
      been shown to interact with scaffolding and signaling proteins via its
      intracellular domain in a phosphorylation-dependent manner and to function as a
      co-receptor partnering with other cell surface or integral membrane proteins.
      This multi-talented receptor has been implicated in regulation of platelet
      derived growth factor receptor activity, integrin maturation and recycling, and
      focal adhesion disassembly. These functions may account for recent studies
      identifying LRP's role in protection of the vasculature, regulation of cell
      migration, and modulation of the integrity of the blood-brain barrier.

PMID- 16102057
TI  - Fibrinogen and fibrin structure and functions.
AB  - Fibrinogen molecules are comprised of two sets of disulfide-bridged Aalpha-,
      Bbeta-, and gamma-chains. Each molecule contains two outer D domains connected to
      a central E domain by a coiled-coil segment. Fibrin is formed after thrombin
      cleavage of fibrinopeptide A (FPA) from fibrinogen Aalpha-chains, thus initiating
      fibrin polymerization. Double-stranded fibrils form through end-to-middle domain
      (D:E) associations, and concomitant lateral fibril associations and branching
      create a clot network. Fibrin assembly facilitates intermolecular antiparallel C
      terminal alignment of gamma-chain pairs, which are then covalently 'cross-linked'
      by factor XIII ('plasma protransglutaminase') or XIIIa to form 'gamma-dimers'. In
      addition to its primary role of providing scaffolding for the intravascular
      thrombus and also accounting for important clot viscoelastic properties,
      fibrin(ogen) participates in other biologic functions involving unique binding
      sites, some of which become exposed as a consequence of fibrin formation. This
      review provides details about fibrinogen and fibrin structure, and correlates
      this information with biological functions that include: (i) suppression of
      plasma factor XIII-mediated cross-linking activity in blood by binding the factor
      XIII A2B2 complex. (ii) Non-substrate thrombin binding to fibrin, termed
      antithrombin I (AT-I), which down-regulates thrombin generation in clotting
      blood. (iii) Tissue-type plasminogen activator (tPA)-stimulated plasminogen
      activation by fibrin that results from formation of a ternary tPA-plasminogen
      fibrin complex. Binding of inhibitors such as alpha2-antiplasmin, plasminogen
      activator inhibitor-2, lipoprotein(a), or histidine-rich glycoprotein, impairs
      plasminogen activation. (iv) Enhanced interactions with the extracellular matrix
      by binding of fibronectin to fibrin(ogen). (v) Molecular and cellular
      interactions of fibrin beta15-42. This sequence binds to heparin and mediates
      platelet and endothelial cell spreading, fibroblast proliferation, and capillary
      tube formation. Interactions between beta15-42 and vascular endothelial (VE)
      cadherin, an endothelial cell receptor, also promote capillary tube formation and
      angiogenesis. These activities are enhanced by binding of growth factors like
      fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF),
      and cytokines like interleukin (IL)-1. (vi) Fibrinogen binding to the platelet
      alpha(IIb)beta3 receptor, which is important for incorporating platelets into a
      developing thrombus. (vii) Leukocyte binding to fibrin(ogen) via integrin
      alpha(M)beta2 (Mac-1), which is a high affinity receptor on stimulated monocytes
      and neutrophils.

PMID- 16102058
TI  - Sexual arousal patterns of bisexual men.
AB  - There has long been controversy about whether bisexual men are substantially
      sexually aroused by both sexes. We investigated genital and self-reported sexual
      arousal to male and female sexual stimuli in 30 heterosexual, 33 bisexual, and 38
      homosexual men. In general, bisexual men did not have strong genital arousal to
      both male and female sexual stimuli. Rather, most bisexual men appeared
      homosexual with respect to genital arousal, although some appeared heterosexual.
      In contrast, their subjective sexual arousal did conform to a bisexual pattern.
      Male bisexuality appears primarily to represent a style of interpreting or
      reporting sexual arousal rather than a distinct pattern of genital sexual
      arousal.

PMID- 16102059
TI  - Sequential effects of phonological priming in visual word recognition.
AB  - Two masked priming experiments were conducted to examine phonological priming of
      bisyllabic words in French, and in particular, whether it operates sequentially
      or in parallel. Bisyllabic target words were primed by pseudowords that shared
      either the first or the second phonological syllable of the target. Overlap of
      the first syllable only-not the second-produced facilitation in both the lexical
      decision and the naming tasks. These findings suggest that, for polysyllabic
      words, phonological codes are computed sequentially during silent reading and
      reading aloud.

PMID- 16102060
TI  - Discounting and conditionalization.
AB  - When people are asked to judge the strengths of two potential causes of an
      effect, they often demonstrate discounting--devaluing the strength of a target
      cause when it is judged in the presence of a strong (relative to a weak)
      alternative cause. Devaluing the target cause sometimes results from
      conditionalization--holding alternative causes constant while evaluating the
      target cause. Yet discounting not attributable to conditionalization also occurs.
      We sought to dissociate conditionalization and discounting (beyond that accounted
      for by conditionalization) by having subjects perform either a spatial or a
      verbal working memory task while learning a causal relation. Conditionalization
      was disrupted by the verbal task but not the spatial task; however, discounting
      was disrupted by the spatial task but not the verbal task. Conditionalization and
      discounting are therefore cognitively dissociable processes in human causal
      inference.

PMID- 16102061
TI  - Familiarity breeds searching: infants reverse their novelty preferences when
      reaching for hidden objects.
AB  - What infants appear to know depends heavily on how they are tested. For example,
      infants seem to understand object permanence (that objects continue to exist when
      no longer perceptible) within the first few months of life when this
      understanding is assessed through looking measures, but not until several months
      later when it is assessed through search measures. One explanation of such
      results is that infants gradually develop stronger representations of objects
      through experience, and that stronger representations are required for some tasks
      than for others. The current study confirms one prediction from this account:
      Stronger representations of familiar objects (relative to novel objects) should
      support greater sensitivity to their continued existence. After seeing objects
      hidden, infants reached more for familiar than novel objects, in striking
      contrast to their robust novelty preferences with visible objects. Theoretical
      implications concerning the origins of knowledge are discussed.

PMID- 16102062
TI  - Can a self-propelled box have a goal? Psychological reasoning in 5-month-old
      infants.
AB  - Some researchers have suggested that infants' ability to reason about goals
      develops as a result of their experiences with human agents and is then gradually
      extended to other agents. Other researchers have proposed that goal attribution
      is rooted in a specialized system of reasoning that is activated whenever infants
      encounter entities with appropriate features (e.g., self-propulsion). The first
      view predicts that young infants should attribute goals to human but not other
      agents; the second view predicts that young infants should attribute goals to
      both human and nonhuman agents. The present research revealed that 5-month-old
      infants (the youngest found thus far to attribute goals to human agents) also
      attribute goals to nonhuman agents. In two experiments, infants interpreted the
      actions of a self-propelled box as goal-directed. These results provide support
      for the view that from an early age, infants attribute goals to any entity they
      identify as an agent.

PMID- 16102063
TI  - Less is more: executive function and symbolic representation in preschool
      children.
AB  - Executive function is recognized as a critical component of children's cognitive
      and social development. In two studies, a measure of executive function that had
      been used in research with chimpanzees was adapted for preschoolers. On this
      task, called Less Is More, children must point to a smaller reward (two candies)
      to receive a larger reward (five candies). In Study 1 (N= 101), performance was
      significantly related to age (3 vs. 4), verbal ability, and established measures
      of executive function. In Study 2 (N= 128), symbolic representations substituted
      for real candies in this task. Three-year-olds' performance improved
      significantly as a function of symbolic distancing. This research has
      implications for the role of symbol systems in the development of executive
      control over thought and action.

PMID- 16102064
TI  - Subliminal speech priming.
AB  - We present a novel subliminal priming technique that operates in the auditory
      modality. Masking is achieved by hiding a spoken word within a stream of time
      compressed speechlike sounds with similar spectral characteristics. Participants
      were unable to consciously identify the hidden words, yet reliable repetition
      priming was found. This effect was unaffected by a change in the speaker's voice
      and remained restricted to lexical processing. The results show that the speech
      modality, like the written modality, involves the automatic extraction of
      abstract word-form representations that do not include nonlinguistic details. In
      both cases, priming operates at the level of discrete and abstract lexical
      entries and is little influenced by overlap in form or semantics.

PMID- 16102065
TI  - The least likely of times: how remembering the past biases forecasts of the
      future.
AB  - Atypical events are both memorable and unrepresentative of their class. We tested
      the hypotheses that (a) people tend to recall atypical instances of events, and
      (b) when they are unaware of this, they rely on these atypical instances in
      forecasting their affective reactions to future events. In three studies,
      participants who were asked to recall an instance of an event and participants
      who were asked to recall an atypical instance of an event recalled equally
      atypical instances. However, only the former participants made extreme forecasts
      about their reactions to future events. The results suggest that the impact bias
      (the tendency to overestimate the affective impact of future events) may be due
      in part to people's reliance on highly available but unrepresentative memories of
      the past.

PMID- 16102066
TI  - How global versus local perception fits regulatory focus.
AB  - We propose a reciprocal relation between regulatory-focus systems and global
      versus local processing styles-specifically, that global processing fits a
      promotion focus on advancement, whereas local processing fits a prevention focus
      on security. In Study 1, participants were shown large letters made of small
      letters and decided if either of two specific letters appeared on the screen.
      Strength of promotion focus was positively correlated with speed of processing
      global letters and negatively correlated with speed of processing local letters,
      whereas the reverse was true for strength of prevention focus. In Study 2,
      participants first worked on a global or local task and later chose between two
      objects. Consistent with our fit proposal, participants who had performed the
      global task assigned a higher price to their chosen object if they had chosen it
      in a promotive, eager manner than if they had chosen it in a preventive, vigilant
      manner, whereas the reverse was true for participants who had performed the local
      task.

PMID- 16102067
TI  - Independent resources for attentional tracking in the left and right visual
      hemifields.
AB  - The ability to divide attention enables people to keep track of up to four
      independently moving objects. We now show that this tracking capacity is
      independently constrained in the left and right visual fields as if separate
      tracking systems were engaged, one in each field. Specifically, twice as many
      targets can be successfully tracked when they are divided between the left and
      right hemifields as when they are all presented within the same hemifield. This
      finding places broad constraints on the anatomy and mechanisms of attentive
      tracking, ruling out a single attentional focus, even one that moves quickly from
      target to target.

PMID- 16102068
TI  - Attention alters the appearance of spatial frequency and gap size.
AB  - Transient attention is the automatic and short-lasting preferential processing of
      an area in visual space initiated by sudden stimulation in the same vicinity.
      Transient attention enhances early visual processing in a variety of dimensions,
      increasing contrast sensitivity, spatial resolution, and acuity. A recent study
      established that the increase in contrast sensitivity is accompanied by an
      increase in apparent contrast. In the present study, we investigated whether the
      effects of transient attention on spatial resolution and acuity are accompanied
      by corresponding phenomenological changes in these dimensions. The data indicate
      that transient attention increases the apparent spatial frequency of Gabor
      stimuli (Experiment 1) and increases apparent gap size in a Landolt-square acuity
      task (Experiment 2). Transient attention not only affects basic visual processing
      it changes what one experiences.

PMID- 16102069
TI  - The meaning of "natural": process more important than content.
AB  - The meaning of the desirable attribute "natural" was explored in two samples,
      American college students and adults in the Philadelphia jury pool. Participants
      rated the naturalness of a variety of "natural" entities, before and after they
      were transformed by operations such as freezing, adding or removing components,
      mixing with other natural or unnatural entities, domestication, and genetic
      engineering. Results support four hypotheses. First, the principle of contagion
      accounts for many aspects of the reduction of naturalness by contact with
      unnatural entities. Second, chemical transformations reduce naturalness much more
      than physical transformations do. Third, the history of an entity's processing is
      more important in determining its naturalness than is the nature of the entity's
      contents. Fourth, mixing like natural entities (e.g., water from different
      sources) does not markedly reduce naturalness. The insertion of a gene from
      another species, the process used in producing genetically modified organisms,
      produces the biggest drop in naturalness; domestication, a human-accomplished
      activity that changes genotype and phenotype in major ways, is considered much
      less damaging to naturalness.

PMID- 16102070
TI  - Youth bulges, civic knowledge, and political upheaval.

PMID- 16102071
TI  - Knowledge, youth bulges, and rebellion.

PMID- 16102072
TI  - A Focus on Human Pigmentary Diseases. Abstracts of the 19th International Pigment
      Cell Conference, September 18-22, 2005, Reston, Virginia, USA.

PMID- 16102073
TI  - Association between diet, social resources and oral health related quality of
      life in edentulous patients.
AB  - To assess whether there was an association between diet, oral health related
      quality of life and social resources in a population of older edentulous adults,
      and, to assess the impact of provision of new complete replacement dentures. This
      study was carried out at Cork University Dental Hospital in Ireland. In this
      prospective clinical study, 35 edentulous adults who requested new complete
      dentures completed pre-treatment questionnaires which included validated oral
      health status, social resources and nutritional assessment questionnaires. New
      dentures were provided and the impact of treatment on oral health related quality
      of life, diet and ability to chew food was assessed. Satisfaction with dentures
      and oral health related quality of life improved following provision of new
      dentures. However, food choice remained similar to pre-treatment choice, and
      subjects were rated as medium risk for poor nutritional status on the Mini
      Nutritional Assessment (MNA) score. Oral health related quality of life and diet
      were not correlated. Three quarters of the sample felt they had no nutritional
      problems. However, approximately 70% reported that they had changed their food
      choices because of dental problems and that financial cost was a barrier to
      dental treatment. Food selection among the group studied was not ideal, and not
      improved by the provision of new dentures. There was no association between diet
      and oral health related quality of life. Further research is needed to improve
      our understanding of the relationship between oral health and diet.

PMID- 16102074
TI  - Detection of improvement in the masticatory function from old to new removable
      partial dentures using mixing ability test.
AB  - The aim of this study was to determine the sensitivity of the Mixing Ability Test
      to detect improvement of masticatory function in subjects on transition from old
      to new removable partial dentures. Thirty-two subjects (seven males, 25 females,
      mean age 65.0 years) with distal extension partially edentulous area in mandible
      and/or maxilla participated in the study. The following reasons were presented
      for replacing the old removable partial dentures with new ones: fracture and/or
      poor fitness of retainers, extraction of abutment teeth, poor fitness of denture
      base, severe wear of artificial teeth and request for metal base dentures.
      Masticatory function with old and new removable partial dentures after an
      adaptation period (mean 27.4 weeks) was evaluated by the Mixing Ability Test.
      Subjects were asked to masticate five two-coloured wax cubes with each removable
      partial denture. Mixing Ability Index was obtained from the colour mixture and
      shape of the masticated cubes. Wilcoxon signed-rank test was used to test the
      difference of Mixing Ability Indexes between old and new removable partial
      dentures. The mixing ability indexes with new removable partial dentures (mean+/-
      s.d.: 0.70+/- 0.68) was significantly higher (P<0.001) than those with old
      removable partial dentures (-0.11+/-1.13). The results suggest that the Mixing
      Ability Test was capable of detecting improvement in masticatory function with
      new removable partial dentures.

PMID- 16102075
TI  - Effects of defect configuration, size, and remaining teeth on masticatory
      function in post-maxillectomy patients.
AB  - The aim of this study was to investigate the correlation between the masticatory
      function and the maxillary defect configuration, size, and remaining teeth in
      post-maxillectomy patients restored with an obturator prosthesis. Fifty
      consecutive post-maxillectomy patients (mean age 67.0) participated in this
      study. The subjects consisted of 26 dentate and 24 edentulous patients. Data were
      collected from the patients' clinical records, diagnostic casts, and a
      questionnaire on masticatory function to evaluate the defect configuration, size,
      and the masticatory function scores associated with wearing obturator prostheses.
      The defect size was evaluated by the ratio of defect area to the horizontal
      impression area. The defect configuration was assessed according to Aramany's
      classification and separated into unilateral and bilateral defects. The multiple
      regression analysis and the Mann-Whitney U-test (P<0.05) were used to assess
      statistical significance. The Spearman's correlation coefficient by rank test was
      also used to detect correlation. The following conclusions were made: (i) The
      presence of teeth in the maxillary dentition and the different type of the defect
      configuration had significant correlation with the masticatory function score
      (r=0.616). (ii) The masticatory function scores of the subjects differed
      significantly with the presence of teeth in the maxillary dentition and the
      different types of defect configurations (P=0.005, P=0.002, respectively). (iii)
      There was significant correlation between the masticatory function score and the
      size of the defect area in the edentulous group (r=-0.648, P=0.001). The presence
      of teeth, the size and configuration of the defect influenced the masticatory
      function of post-maxillectomy patients with obturator prostheses.

PMID- 16102076
TI  - Midfacial and mandibular morphometry of children with Class II and Class III
      malocclusions.
AB  - There is insufficient evidence in conventional cephalometric analysis of the
      actual sites of putative maxillofacial change in Class II and Class III
      malocclusions. The purpose of this study was to provide more information about
      the morphological characteristics of the midfacial complex and mandible in
      children with Class II or III malocclusions. Seventy children with Class II,
      division 1 malocclusion and 70 children with Class III malocclusion were compared
      with 70 children with normal occlusion. This study was conducted to carry out
      geometric morphometric assessments to localize alterations using Procrustes
      analysis and thin-plate spline analysis. Procrustes analysis indicated the
      midfacial and mandibular morphologies differed between normal occlusion subjects
      and subjects with Class II or Class III malocclusion (P<0.0001). The deformations
      in subjects with Class II malocclusion may represent a developmental elongation
      of the palatomaxillary complex and a shortening of the mandible
      anteroposteriorly, which leads to the appearance of a protruding midface and
      retruding mandibular profile. In contrast, the deformations in subjects with
      Class III malocclusion may represent a developmental shortening of the
      palatomaxillary complex and elongation of the mandible anteroposteriorly, which
      leads to the appearance of a retrognathic midface and prognathic mandibular
      profile.

PMID- 16102077
TI  - Flexure deformation in temporomandibular joint disk displacement without
      reduction may predict treatment outcome.
AB  - To identify whether the direction of disk flexure deformation predicts the
      prognosis in cases of anterior disk displacement without reduction of painful
      temporomandibular joint (TMJ), the relationship between the direction of flexure,
      observed on pseudodynamic magnetic resonance (MR) images, and the outcome of
      conservative treatment using a flat occlusal splint was analysed in 40 female
      patients who perceived occasional or constant pain at unilateral TMJ with disk
      displacement without reduction. From the MR findings, 20 patients were classified
      as having upward flexure deformation of the disk and 20 as having downward
      flexure deformation. Patients' TMJ pain, masticatory muscle pain, amount of
      maximal mouth opening, and MR findings were evaluated before treatment. All
      patients were treated with a flat occlusal splint for 6 months. The patients'
      signs and symptoms were analysed statistically within each group before treatment
      and 3 and 6 months afterwards, and were also compared between the upward and
      downward flexure groups. There was no statistical difference between the groups
      before treatment, except in the amount of maximal mouth opening and the extent of
      disk displacement. The upward flexure group had persistent TMJ pain and tendency
      of delayed alleviation of masticatory muscle pain compared with the downward
      flexure group, although maximal opening gradually increased in both groups. Thus,
      the direction of the flexure in deformation of the disk, which can be observed
      only with pseudodynamic MR imaging, may predict the prognosis of painful disk
      displacement without reduction following treatment with a flat occlusal splint.

PMID- 16102078
TI  - Efficacy of a posterior implant support for extra shortened dental arches: a
      biomechanical model analysis.
AB  - The purpose of this study was to test the efficacy of utilizing implants
      underneath distal free-end denture bases to establish a stable occlusal support
      for extreme shortened dental arches (ESDA). The authors constructed a two
      dimensional finite element model of the ESDA where only lower anterior teeth
      remain. Posterior occlusal support was provided by a fixed partial denture with
      an osseointegrated implant (IFPD), fixed cantilever partial denture (CFPD), or a
      removable partial denture with or without an implant underneath (IRPD and RPD). A
      dentate mandible model was the control. When muscle vectors simulating clenching
      force were applied, stress levels on the temporal bone surface area under each
      configuration were compared, to evaluate the efficacy in establishing the
      occlusal support. The largest stress increase in temporal bone was found in the
      ESDA situation followed by the RPD. The least amount of stress increase was found
      with the IFPD followed by IRPD when the implant was placed in the molar region.
      The stress increase with IRPD was about 20-45% of the amount with RPD. Our
      results suggest that IFPD provides most favourable and stable occlusal support,
      however, IRPD with a single posterior implant also provide stable occlusal
      support with reducing the stress levels in the temporomandibular joint.

PMID- 16102079
TI  - Prevention of postoperative tooth sensitivity: a preliminary clinical trial.
AB  - The purpose of this study was to evaluate clinically the effects of pre
      treatments with a 35% hydroxyethyl metacrylate/5% glutaraldehyde dentine
      desensitizer (Gluma Desensitizer) and a 2% chlorexidine-based cavity disinfectant
      (Cav-Clean) on postoperative sensitivity. Three premolar teeth with no pain
      symptoms were selected from each one of 17 patients, totalling 51 teeth, for
      which Class II restoration using a composite was indicated. Each one of the three
      premolar teeth of the same patient was submitted to a different treatment. After
      acid etching, only a dental adhesive was applied to the first tooth, which served
      as the control. Gluma Desensitizer dentinal desensitizer was applied to the
      second premolar tooth prior to applying the dental adhesive. Cav-Clean cavity
      disinfectant was used on the third premolar tooth before applying the dental
      adhesive. Only one tooth was restored per session, and all premolar teeth were
      restored with a condensable composite, according to current restoration technique
      guidelines. Sensitivity to different stimuli (cold, heat, sweet and dental floss)
      was assessed on Day 1, Day 4 and Day 7 by questionnaire following restorative
      procedures. The results of this clinical research showed that, as far as the
      investigated stimuli and postoperative course are concerned, there was no
      statistically significant difference in the three different treatments (P>0.05).
      Postoperative sensitivity resulting from Class II restorations using composite
      resin cannot be completely eliminated with the prior use of a dentinal
      desensitizer or a cavity disinfectant. In day-to-day clinical treatment,
      postoperative sensitivity may possibly be related to the technique employed.

PMID- 16102080
TI  - Effect of APF gel on micromorphology of resin modified glass-ionomer cements and
      flowable compomers.
AB  - The purpose of this study was to evaluate the surface micromorphology of resin
      modified glass-ionomer cements and flowable compomers. In the study two resin
      modified glass-ionomers and two flowable compomers were used to prepare
      standardized 20 cylinderic samples. Samples were divided into four groups.
      Surface treatments with APF gel for experimental groups (group B,C,D) or
      distilled water as a control (group A) were performed four times. In group B,
      only APF gel was applied. In group C, after the APF gel application, the samples
      were immersed into the demineralizing and remineralizing solutions. In group D,
      before the APF gel application, the buffer solution was applied. The examinations
      of the surface micromorphology of the materials were made by using scanning
      electron microscope (SEM). Results showed that in group B all of the materials
      except Compoglass Flow, and in group C all of the materials showed erratic
      behaviours. In group D, severe erratic effect (score 2) was obtained on the
      surfaces of Vivaglassliner and Dyract Flow, and for the others score 1 signals
      were found. The moderate degradation was obtained by applying of only APF gel on
      the surfaces of both material groups. The addition of pH circulation caused
      increasing of micromorphologic changes on the surfaces of all materials. The
      effect of application of buffer solution on the surfaces before APF gel changed
      according to the materials. If acidulated fluoride gel is preferred for
      prophylactic therapy in patients' mouth, for the success, either buffer or
      neutral fluoride have to be applied on the restored teeth by resin based
      materials before acidulated fluoride application.

PMID- 16102081
TI  - Microleakage of class V resin composite restorations after conventional and
      Er:YAG laser preparation.
AB  - This in vitro study compared the microleakage of Class V resin composite
      restorations at bevelled enamel/composite and dentin/composite interfaces
      following Er:YAG laser (pre-treatment modalities: laser-etching and/or acid
      etching) or conventional preparation and acid-etch, in association with two resin
      composite formulations and their three-step adhesive system. Class V cavities
      with conventional bevel produced on the lingual and buccal surfaces of eighty
      extracted caries- and restoration-free human teeth, were assigned to eight
      groups: cavities were or Er:YAG-lased and acid-etched (groups 1 and 5); or Er:YAG
      lased, laser-etched and acid-etched (groups 2 and 6); or Er:YAG-lased and only
      laser-etched (groups 3 and 7); or cut by dental drill at high-speed and acid
      etched (groups 4 and 8). The specimens were restored with Optibond FL+Herculite
      XRV (groups 1, 2, 3 and 4) or with Scotchbond MP+Z 100 (groups 5, 6, 7 and 8),
      stored in distilled water at 37 degrees C for 24 h, thermocycled 1500 times
      between 5 and 55 degrees C, placed in a 2% aqueous solution of methylene blue for
      24 h at 37 degrees C, embedded in resin and sectioned. Microleakage was assessed
      according to the depth of dye penetration along the restoration. There were
      statistically significant differences between occlusal and cervical regions for
      all groups (P<0.01) except for groups 3 and 7. Pair-wise comparison of groups
      showed that acid-etch is advocated when using resin composite in Er:YAG-lased
      Class V cavities; the seal at enamel margins in Er:YAG-lased and laser-etched
      cavities depended on the resin composite formulation and corresponding adhesive
      (P<0.05).

PMID- 16102082
TI  - Laboratory study of the loads, speeds and times to finish and polish direct
      restorative materials.
AB  - This study investigated the loads, speeds and times required to achieve the
      smoothest surface on samples of amalgam, composite resin and glass-ionomer cement
      using the four grades of a disc polishing system. The tests were conducted on a
      specially constructed jig. The restorations were abraded with the appropriate
      disc using a range of loads, speeds and times based on a previous practitioner
      study. The surface roughness of each material was measured before and after
      abrading. The load was varied first, followed by speed and finally time.
      Photomicrographs were taken of a sample finished at the optimum load, speed and
      time and of loads above and below the optimum that produced the smoothest surface
      finish. In addition the fractured edge of a sample finished at the optimum values
      was examined. There was an optimum load, speed and time that produced the
      smoothest surface for each restorative material. For amalgam and composite the
      surface roughness value decreased as the discs became finer. There was a
      reduction in the roughness value for glass-ionomer cement using the two roughest
      discs. The values obtained were substantially in contrast from the earlier
      practitioner study. There were specific values for load, speed and time that
      produced a smoother surface for each material.

PMID- 16102083
TI  - Use of biofunctional prosthetic system following partial maxillary resection: a
      clinical report.
AB  - This clinical report describes the prosthodontic rehabilitation of an edentulous
      patient with a maxillary defect using the biofunctional prosthetic system. The
      Biofunctional Prosthetic System brand denture includes a comprehensive technique
      for impressions, record taking, tooth placement, fabrication and processing. The
      advantage of this technique is to provide patients with optimal form, function,
      and aesthetics in complete dentures. This system is based on a team effort and
      systematic approach to removable prosthetic treatment.

PMID- 16102084
TI  - A prosthodontic management alternative for scleroderma patients.
AB  - Hardening of the skin around the mouth causes the oral opening to become limited
      in scleroderma patients. A maximal oral opening that is smaller than the size of
      a complete denture can make prosthetic treatment challenging. This clinical
      report presents the prosthodontic management of a total edentulous patient with
      microstomia induced by scleroderma. Sectional mandibular and maxillary trays and
      a collapsed mandibular denture were fabricated for the total edentulous patient.
      With the use of lingual midline hinge, the collapsed denture was successfully and
      easily inserted and provided adequate function in the patient's mouth. The cast
      hinge design reduced the overall costs and simplified the laboratory technique.

PMID- 16102085
TI  - Youth voices as change agents: moving beyond the medical model in school-based
      health center practice.
AB  - This article describes a 34-week pilot project aimed at improving health care
      service delivery for adolescents by offering youth a distinct role as advisory
      board members who help shape policy, provide feedback, guidance, and direction to
      a school-based health center (SBHC) program in Boston. Freshmen were recruited to
      participate in a Youth Advisory Board Project that included weekly afterschool
      meetings. Adult supervision was provided by SBHC staff that included 2 clinical
      social workers and 1 youth empowerment specialist. Through this effort, students
      were (1) trained in nonprofit board development and governance structures; (2)
      urged to identify gaps in services; (3) taught to select, prioritize, and
      implement action projects; and (4) offered clinical support around personal
      issues. Students brought a wealth of life experiences, knowledge of teen
      attitudes, information regarding trends in risk-taking behaviors, and feedback
      about experiences in the SBHC. In addition, their increased awareness of the SBHC
      service elements led to identification of obstacles to youth participation in
      care, feedback regarding positive and negative health care experiences within the
      SBHC, as well as with external health care providers, and ideas about
      unrecognized needs leading to gaps in services. This experience demonstrated that
      young health care consumers, with support, can focus their attention and begin to
      utilize analytical thinking skills to shape health outcomes and inform service
      delivery.

PMID- 16102086
TI  - The small schools movement: implications for health education.
AB  - Approximately 70% of American high schools enroll 1000 or more students each,
      while almost one half of high schools enroll more than 1500 students each. A
      growing body of evidence, however, is showing that small schools, especially
      small secondary schools, result in positive benefits for students, families, and
      communities that go beyond letter grades. Investigators have found that smaller
      high schools result in greater academic achievement, higher faculty morale, less
      student misbehavior, and greater family satisfaction. Recommended strategies to
      create a more personalized high school experience and improve performance include
      creating smaller "schools" within large schools, instituting career academies,
      reworking the school day, and employing teacher advisory systems. This article
      describes the prominent elements of effective small schools with implications for
      a strengthened "presence" of the coordinated school health program at the high
      school level.

PMID- 16102087
TI  - Sleep and student performance at school.
AB  - To review the state of research on the association between sleep among school
      aged children and academic outcomes, the authors reviewed published studies
      investigating sleep, school performance, and cognitive and achievement tests.
      Tables with brief descriptions of each study's research methods and outcomes are
      included. Research reveals a high prevalence among school-aged children of
      suboptimal amounts of sleep and poor sleep quality. Research demonstrates that
      suboptimal sleep affects how well students are able to learn and how it may
      adversely affect school performance. Recommendations for further research are
      discussed.

PMID- 16102088
TI  - Chronic health conditions and student performance at school.
AB  - To review the state of research on the association between common chronic health
      conditions and academic outcomes, the authors reviewed published studies
      investigating the association of school attendance, cognitive ability, and
      achievement with a number of chronic diseases. Tables with brief descriptions of
      each study's research methods and outcomes are included. Research reveals
      evidence that diabetes, sickle cell anemia, and epilepsy affect student
      achievement and ability. Levels of academic deficiency and specific areas of
      cognitive impairment are not as well understood. Many chronic conditions are not
      well researched. Suggestions for further research and recommendations for
      educators and health practitioners are provided.

PMID- 16102089
TI  - How attrition impacts the internal and external validity of longitudinal
      research.

PMID- 16102090
TI  - Lights, camera, action: integrating popular film in the health classroom.

PMID- 16102091
TI  - Parental vaccine beliefs and child's school type.

PMID- 16102092
TI  - Big piece, little piece or: yes, factor VIII is a protein.

PMID- 16102093
TI  - Is APC activation of endothelial cell PAR1 important in severe sepsis?: No.

PMID- 16102094
TI  - Is APC activation of endothelial cell PAR1 important in severe sepsis?: Yes.

PMID- 16102095
TI  - Coagulation biology in glioma pathogenesis: a missing link?

PMID- 16102096
TI  - Computed tomography for pulmonary embolism diagnosis: the making of a reference
      standard.

PMID- 16102097
TI  - Management of suspected pulmonary embolism (PE) by D-dimer and multi-slice
      computed tomography in outpatients: an outcome study.
AB  - OBJECTIVES: A prospective outcome study designed to evaluate a simple strategy
      for the management of outpatients with suspected pulmonary embolism (PE), based
      on clinical probability, D-dimer, and multi-slice computed tomography (MSCT).
      METHODS: A cohort of 432 consecutive patients admitted to the emergency
      department with suspected PE was managed by sequential non-invasive testing.
      Patients in whom PE was ruled out were not given anticoagulants, but were
      followed-up for 3 months. RESULTS: Normal D-dimer and low-intermediate clinical
      probability ruled out PE in 103 patients [24% (95% CI 20-28)]. Seventeen patients
      had normal D-dimer, but high clinical probability and proceeded to MSCT. All
      patients proved negative for PE. A total of 329 (76%) patients underwent MSCT
      examination. Pulmonary embolism was diagnosed in 93 patients [21.5% (95% CI 18
      26)] and was ruled out by negative MSCT in 221 patients [51% (95% CI 46-56)].
      MSCT scans were determined as inconclusive in 15 (4.5%) patients. No patient
      developed objectively verified venous thromboembolism (VTE) during the 3-month
      follow-up period. However, the cause of death was adjudicated as possibly related
      to PE in two patients, resulting in an overall 3-month VTE risk of 0.6% (95% CI 0
      2.2%). The diagnostic algorithm yielded a definite diagnosis in 96.5% of the
      patients. CONCLUSIONS: This simple and non-invasive strategy combining clinical
      probability, D-dimer, and MSCT for the management of outpatients with suspected
      PE appears to be safe and effective.

PMID- 16102098
TI  - Hemorrhage following hematopoetic stem cell transplantation--which arrows belong
      in the quiver?

PMID- 16102099
TI  - Recombinant activated factor VII in treatment of bleeding complications following
      hematopoietic stem cell transplantation.
AB  - BACKGROUND: Bleeding is a common complication following hematopoietic stem cell
      transplantation (HSCT) and standard hemostatic treatment is often ineffective. We
      conducted a multicentre, randomized trial of the efficacy and safety of activated
      recombinant factor VII (rFVIIa, NovoSeven) in the treatment of bleeding following
      HSCT. METHODS: 100 patients with moderate or severe bleeding (52
      gastrointestinal; 26 hemorrhagic cystitis; seven pulmonary; one cerebral; 14
      other) were included from days +2 to +180 post-transplant (97 allogeneic; three
      autologous) to receive seven doses of rFVIIa (40, 80 or 160 microg kg(-1)) or
      placebo every 6 h. The primary efficacy endpoint was the change in bleeding score
      between the first administration and 38 h. RESULTS: No significant effect of
      increasing rFVIIa dose was observed on the primary endpoint. A post hoc analysis
      comparing each rFVIIa dose with placebo showed that 80 microg kg(-1) rFVIIa
      improved the bleeding score at the 38 h time point (81% vs. 57%, P = 0.021). This
      effect was not seen at 160 microg kg(-1). There were no differences in
      transfusion requirements across dose groups. There was no trend in the type or
      number of severe adverse events observed. Six thromboembolic events were observed
      in the active treatment groups: three during, and three following the 96-h
      observation period. CONCLUSIONS: Despite no overall effect of rFVIIa treatment on
      primary endpoint, post hoc analysis showed an improvement in the control of
      bleeding for 80 microg kg(-1) rFVIIa vs. standard hemostatic treatment. The
      heterogeneity of the population may have contributed to the lack of an increasing
      effect with increased dose. Further trials should focus upon identifying the
      patient populations that may benefit from treatment with rFVIIa.

PMID- 16102100
TI  - Local fibrinolysis.

PMID- 16102101
TI  - Cardiac fibrinolytic capacity is markedly increased after brief periods of local
      myocardial ischemia, but declines following successive periods in anesthetized
      pigs.
AB  - BACKGROUND: Fibrinolysis in blood is mainly reflected by the activities of tissue
      plasminogen activator (tPA) and of plasminogen activator inhibitor-1 (PAI-1). The
      effect of myocardial ischemia on their activities in the coronary circulation is,
      however, not established. OBJECTIVES: With an improved experimental model, we
      therefore examined the effect of a brief period of myocardial ischemia on their
      activities. Furthermore, the consequences of repeated periods of ischemia,
      mimicking the situations in patients with unstable angina, were investigated.
      METHODS: In six anesthetized pigs, we occluded the distal left anterior
      descending coronary artery (LAD) four times for 10 min with 40 min intervals and
      determined the activities of tPA and PAI-1 in arterial and coronary venous blood.
      By simultaneously recording LAD flow, we could estimate cardiac release of these
      factors at baseline conditions and during reperfusion. RESULTS: Neither net
      cardiac release of PAI-1 nor alterations in plasma PAI-1 levels were demonstrated
      during the experiment. However, a significant net release of tPA activity of 10.4
      +/- 3.2 IU mL(-1) (P < 0.005) was recorded during baseline conditions. During
      reperfusion following the first period of ischemia, the cardiac release of tPA
      activity increased to a peak of 103 +/- 30-fold baseline release, but declined
      progressively after repeated periods of ischemia. After the fourth period, tPA
      release did not exceed an estimated baseline accumulation during ischemia and
      early reperfusion. CONCLUSIONS: In this porcine model, a substantial local
      increase in fibrinolytic capacity was observed after brief periods of ischemia,
      but declined subsequently by repeated periods of ischemia.

PMID- 16102102
TI  - Ambient air pollution and acute myocardial infarction.
AB  - This review summarizes the nature of ambient air pollutants, which are either
      gaseous or particulate of various sizes, the latter determining their penetration
      into the body, the smallest even translocating from the lung into the systemic
      circulation. It presents the epidemiological evidence linking air pollution to
      overall mortality, cardiovascular mortality and myocardial infarction, making the
      distinction between acute and chronic exposure to the pollutants. It reviews
      mechanistic investigations that have evaluated the links among exposure to
      pollutants, thrombosis, pulmonary inflammation, arterial vasoconstriction and
      heart rate variability. It concludes by attempting to integrate current
      epidemiological and mechanistic observations into a pathophysiological framework
      that links ambient air pollution to acute myocardial infarction and
      cardiovascular mortality.

PMID- 16102103
TI  - Novel determinants of plaque instability.
AB  - Arachidonic acid metabolism plays an important role in acute ischemic syndromes
      affecting the coronary or cerebrovascular territory, as reflected by biochemical
      measurements of eicosanoid biosynthesis and the results of inhibitor trials in
      these settings. Two cyclooxygenase (COX)-isozymes have been characterized, COX-1
      and COX-2, that differ in terms of regulatory mechanisms of expression, tissue
      distribution, substrate specificity, preferential coupling to upstream and
      downstream enzymes and susceptibility to inhibition by the extremely
      heterogeneous class of COX-inhibitors. While the role of platelet COX-1 in acute
      coronary syndromes and ischemic stroke is firmly established through
      approximately 20 years of thromboxane metabolite measurements and aspirin trials,
      the role of COX-2 expression and inhibition in atherothrombosis is substantially
      uncertain, because the enzyme was first characterized in 1991 and selective COX-2
      inhibitors became commercially available only in 1998. In this review, we discuss
      the pattern of expression of COX-2 in the cellular players of atherothrombosis,
      its role as a determinant of plaque 'vulnerability,' and the clinical
      consequences of COX-2 inhibition. Recent studies from our group suggest that
      variable expression of upstream and downstream enzymes in the prostanoid
      biosynthetic cascade may represent important determinants of the functional
      consequences of COX-2 expression and inhibition in different clinical settings.

PMID- 16102104
TI  - The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis
      at diagnosis and during treatment.
AB  - BACKGROUND: Thromboembolism can occur during acute leukemia, especially acute
      lymphoid leukemia (ALL) treated with L-asparaginase. Yet, most reports are
      anecdotical and scarce data are available on the risk of thrombosis in acute
      myeloid leukemia (AML). OBJECTIVES: To evaluate the risk of thrombosis in
      patients with acute leukemia. PATIENTS AND METHODS: Three-hundred and seventy
      nine consecutive adult patients with newly diagnosed acute leukemia were
      recruited in an observational cohort study conducted from January 1994 to
      December 2003. Diagnosis was ALL in 69 patients, acute promyelocytic leukemia
      (APL; FAB subtype M3) in 31, and non-M3 AML in 279. All first or recurrent
      symptomatic thromboembolic events objectively diagnosed were recorded. RESULTS:
      Twenty-four patients of the overall 379 (6.3%; 95% CI 4.1%-9.2%) had a first
      thrombosis, venous in 80% of the cases and arterial in 20%. At diagnosis,
      thrombosis was a presenting manifestation in 13 cases (3.4% of the whole cohort):
      1.4% in ALL, 9.6% in APL, and 3.2% in non-M3 AML patients. Follow-up was carried
      out on 343 patients without thrombosis at diagnosis and further 11 thrombotic
      events (3.2%) were recorded. At 6 months from diagnosis, the cumulative incidence
      of thrombosis was 10.6% in ALL, 8.4% in APL, and 1.7% in non-M3 AML patients. The
      patients who received L-asparaginase had a 4.9-fold increased risk of thrombosis
      in comparison with those who did not (95% CI 1.5-16.0). The fatality rate due to
      thrombosis was 0.8%. CONCLUSIONS: In patients with acute leukemia, the risk of
      thrombosis is not negligible. Thombosis can be a presenting symptom at diagnosis
      in a significant portion of cases with APL (9.6%) and non-M3 AML (3.2%); a
      similar rate of thrombosis can occur during the subsequent course of the disease.
      The incidence of symptomatic thrombosis at diagnosis is relatively low in ALL
      patients (1.4%), but is significantly increased by further treatment up to 10.6%.
      Strategies of antithrombotic prophylaxis should be investigated in this setting.

PMID- 16102105
TI  - Lupus anticoagulants and the risk of a first episode of deep venous thrombosis.
AB  - We have determined lupus anticoagulants, anti-beta2 glycoprotein I (beta2GPI) and
      antiprothrombin antibodies in the Leiden Thrombophilia Study, a population-based
      case-control study designed to determine risk factors for deep venous thrombosis
      (DVT). Lupus anticoagulant (LAC) was measured in 473 patients and 472 control
      subjects. Four control subjects (0.9%) and 14 patients (3.1%) had a positive LAC,
      resulting in a 3.6-fold increased risk [odds ratio (OR) 3.6, 95% CI: 1.2-10.9].
      Of the total population, 49 were positive for anti-beta2GPI antibodies: 15
      controls (3.4%) and 34 patients (7.5%), implying a 2.4-fold increased risk (95%
      CI: 1.3-4.2). Antiprothrombin antibodies were present in 114 subjects: 48
      controls (11.0%) and 66 cases (14.6%) with an OR of 1.4 (95% CI: 1.0-2.1). When
      LAC was considered in the co-presence of antiprothrombin or anti-beta2GPI
      antibodies the OR increased to 10.1 (95% CI: 1.3-79.8). A LAC without a positive
      anti-beta2GPI or antiprothrombin test was not associated with a risk for DVT (OR
      1.3, 95% CI: 0.3-6.0). This study demonstrates that the presence of LAC, anti
      beta2GPI antibodies and antiprothrombin antibodies are risk factors for DVT in a
      general population. The strongest association holds for the combination LAC and
      the presence of anti-beta2GPI or antiprothrombin antibodies.

PMID- 16102106
TI  - Stromelysin-1 promoter 5A/6A polymorphism is an independent genetic prognostic
      risk factor and interacts with smoking cessation after index premature myocardial
      infarction.
AB  - OBJECTIVE: To evaluate the prognostic roles of multiple polymorphisms and smoking
      cessation for premature myocardial infarction (MI). METHODS: We studied 170
      patients with MI onset before the age of 45 years (range 27-45 years, 84% men)
      and analyzed the traditional risk factors and several candidate genes'
      associations with their subsequent coronary events. RESULTS: Follow-up data were
      available for a total of 162 individuals (95.3%) with the other 38 individuals
      (4.7%) being lost-to-follow-up premature MI patients. During a mean period of
      4.43 years' follow-up, diabetes mellitus (DM), hypertension, hypercholesterolemia
      and Killip's status > or =II were more frequent among patients with subsequent
      cardiac events (all P-values <0.05). The frequency of 5A allele of stromelysin-1
      gene was significantly higher among event group (P = 0.01). Smoking cessation
      after MI, use of beta-blocker or angiotensin-converting enzyme inhibitor (ACEI)
      could improve outcome (all P-values <0.05). After multivariate analysis, we found
      that DM was an independent risk factor for survival [Hazard ratio (HR) 2.45, P =
      0.01]. Successful smoking cessation and therapy with ACEI could have a protective
      effect (HR 0.33 and 0.09, P = 0.01 and <0.01, respectively). The stromelysin-1 5A
      gene polymorphism was also an independent survival predictor (HR 2.51, P = 0.03).
      In addition, smoking cessation could significantly modify the risk, especially
      among patients with 5A allele polymorphism (HR 6.75 vs. 1.50). CONCLUSION: We
      thus conclude that the stromelysin-1 gene polymorphism alone or in combination
      with smoking cessation can influence the prognosis after index premature MI.

PMID- 16102107
TI  - Venous thromboembolism and mortality after hip fracture surgery: the ESCORTE
      study.
AB  - BACKGROUND: Recent changes in the management of hip fracture surgery patients may
      have modified the epidemiology of postoperative complications. OBJECTIVES: We
      performed an observational study of a cohort of patients undergoing hip fracture
      surgery to update the epidemiological data on this population. The primary study
      outcome was the incidence of confirmed symptomatic venous thromboembolism (VTE)
      [defined as deep vein thrombosis, pulmonary embolism (PE), or both] at 3 months.
      Overall mortality at 1, 3 and 6 months was also evaluated. PATIENTS/METHODS:
      Consecutive patients aged at least 18 years hospitalized in French public or
      private hospitals (531 centers) undergoing hip fracture surgery were recruited
      prospectively during 2 months in 2002 and a follow-up at 6 months. Predictive
      factors for VTE at 3 months and for death at 6 months were also analyzed.
      RESULTS: Data from 6860 (97.3%) of the 7019 recruited patients were included in
      the analysis. The median age was 82 years. Low molecular weight heparins were
      administered perioperatively in 97.6% of patients; 69.5% received this treatment
      for at least 4 weeks. The actuarial rate of confirmed symptomatic VTE at 3 months
      was 1.34% (85 events, 95% CI: 1.04-1.64). There were 16 PEs (actuarial rate:
      0.25%), three of which were fatal. Overall, 1006 (14.7%) patients were dead at 6
      months. Cardiovascular disease was the most frequent cause of death (270
      patients; 26.8%). CONCLUSIONS: The current rate of postoperative VTE is low, but
      overall mortality remains high. Indeed, hip fracture patients belong to a
      vulnerable group of old people with comorbid diseases and a high risk of
      postoperative morbidity and mortality. An interdisciplinary approach could be the
      challenge to improve short and long-term outcome.

PMID- 16102108
TI  - Factor XIII Val34Leu polymorphism and gamma-chain cross-linking at the site of
      microvascular injury in healthy and coumadin-treated subjects.
AB  - Fibrin (Fn) cross-linking by activated factor (F) XIII is essential for clot
      stability. In vitro, a common Leu34 polymorphism of the FXIIIA-subunit increases
      the rate of thrombin-mediated FXIII activation, but not cross-linking activity
      upon complete FXIII activation. The effect of FXIII Val34Leu polymorphism on
      fibrin(ogen) cross-linking in vivo when vascular injury triggers the blood
      coagulation has not been studied yet. Using quantitative immunoblotting with
      antibodies raised against FXIIIA-subunits, fibrinogen, and gamma-gamma-dimers,
      the rates of FXIIIA cleavage and fibrin(ogen) cross-link formation in the fluid
      phase of 30-s blood samples collected at the site of microvascular injury were
      compared in the Leu34-positive and -negative healthy individuals and patients on
      long-term oral anticoagulation. In addition to accelerated FXIII activation, in
      healthy subjects the presence of FXIII Leu34 allele was associated with increased
      soluble gamma-gamma-dimer formation by 40% (1355 +/- 17 microg L(-1) for Leu34
      carriers vs. 804.3 +/- 17 microg L(-1) for Leu34 non-carriers; P = 0.028) at the
      site of microvascular injury. This solution phase effect was abolished in
      coumadin-treated patients (369.4 +/- 75.9 microg L(-1) for Leu34 carriers vs.
      290.5 +/- 35.9 microg L(-1) for Leu34 non-carriers; P > 0.05). The present study
      indicates that the Leu34 allele affects soluble gamma-gamma-dimer formation in
      untreated individuals, but not in those receiving acenocoumarol. Our data may
      help elucidate the impact of the FXIII Val34Leu polymorphism on Fn cross-linking
      in vivo and its modulation by oral anticoagulants.

PMID- 16102109
TI  - Transplantation of endothelial cells corrects the phenotype in hemophilia A mice.
AB  - BACKGROUND: The deficiency of factor VIII, a co-factor in the intrinsic
      coagulation pathway results in hemophilia A. Although FVIII is synthesized
      largely in the liver, the specific liver cell type(s) responsible for FVIII
      production is controversial. OBJECTIVE: This study aimed to determine the
      cellular origin of FVIII synthesis and release in mouse models. METHODS: We
      transplanted cells into the peritoneal cavity of hemophilia A knockout mice.
      Plasma FVIII activity was measured using a Chromogenix assay 2-7 days after cell
      transplantation, and phenotypic correction was determined with tail-clip
      challenge 7 days following cell transplantation. Transplanted cells were
      identified by histologic and molecular assays. RESULTS: Untreated hemophilia A
      mice, as well as mice treated with the hepatocyte-enriched fraction, showed
      extensive mortality following tail-clip challenge. In contrast, recipients of
      unfractionated liver cells (mixture of hepatocytes, liver sinusoidal endothelial
      cells (LSEC), Kupffer cells, and hepatic stellate cells) or of the cell fraction
      enriched in LSECs survived tail-clip challenge (P < 0.001). FVIII was secreted in
      the blood stream in recipients of unfractionated liver cells, LSECs and
      pancreatic islet-derived MILE SVEN 1 (MS1) endothelial cells. Although
      transplanted hepatocytes maintained functional integrity in the peritoneal
      cavity, these cells did not produce detectable plasma FVIII activity.
      CONCLUSIONS: The assay of cell transplantation in the peritoneal cavity showed
      that endothelial cells but not hepatocytes produced phenotypic correction in
      hemophilia A mice. Therefore, endothelial cells should be suitable additional
      targets for cell and gene therapy in hemophilia A.

PMID- 16102110
TI  - Evaluation of the profile of thrombin generation during the process of whole
      blood clotting as assessed by thrombelastography.
AB  - The objective of this study was to evaluate the possibility of linking the
      tracing of whole blood clotting in a thrombelastograph (TEG) hemostasis system
      with the generation of thrombin assessed by thrombin/antithrombin complex (TAT).
      Citrated whole blood containing corn trypsin inhibitor from volunteers was
      clotted in the presence of CaCl2 and tissue factor. Clotting was monitored with
      the eight channels of a TEG system. At different time points, the whole blood TEG
      reaction cups were kept in a cold quenching solution, centrifuged, and the
      supernatants were kept at -80 degrees C until assayed for TAT by ELISA. The total
      thrombus generation (TTG) was calculated from the first derivative of the TEG
      waveform and was compared with thrombin generation measured by TAT. The two
      vector values--the TAT thrombin generation data and the corresponding TEG TTG-
      were analyzed using Pearson correlation coefficients (r) and linear, non-linear
      and natural log (ln) transformation of TAT values for least-squares goodness-of
      fit curves. The best least-squares fit is an exponential curve. Linearizing using
      the ln of the TAT thrombin generation variable produces the same r (0.94) as of
      the exponential curve. The prediction equation is y = 8.0465 + 0.0005x (P < or =
      0.0001), where y is the TAT thrombin generation variable in the ln transformation
      and x is the TEG TTG variable. The high magnitude of r and the high significance
      of the prediction equation demonstrate the high efficacy of the prediction of TAT
      thrombin generation by the use of TEG TTG.

PMID- 16102111
TI  - Molecular models of the procoagulant factor VIIIa-factor IXa complex.
AB  - BACKGROUND: Formation of the intrinsic tenase complex is an essential event in
      the procoagulant reactions that lead to clot formation. The tenase complex is
      formed when the activated serine protease, Factor IXa (FIXa), and its cofactor
      Factor VIIIa (FVIIIa) assemble on a phospholipid surface to proteolytically
      convert the zymogen Factor X (FX) into its active form FXa. The physiological
      relevance of the tenase complex is evident in hemophilia A or B patients who
      present with bleeding disorders. OBJECTIVES: The purpose of this study was to
      establish three-dimensional (3D) models of the FVIIIa-FIXa complex. METHODS:
      First, we built two new theoretical models of FVIIIa via homology modeling, inter
      domain docking and loop simulation algorithms as well as a model for FIXa. This
      was followed by pseudo-Brownian protein-protein docking in internal coordinates
      with the ICM (Internal Coordinates Mechanics) program between the two FVIIIa and
      the FIXa structures. RESULTS: Ten representative models of this complex are
      presented based on agreements with known experimental data and according to
      structural criteria. CONCLUSIONS: These novel 3D models will help guide future
      site directed mutagenesis aimed at improving the functionality of FVIIIa and/or
      FIXa and will contribute to a better understanding of the role of this
      macromolecular complex in the blood coagulation cascade.

PMID- 16102112
TI  - A RUNX/AML-binding motif residing in a novel 13-bp DNA palindrome may determine
      the expression of the proximal promoter of the human uPA gene.
AB  - Urokinase-type plasminogen activator (uPA) is a multifunctional extracellular
      serine protease implicated in different events including fibrinolysis, tissue
      remodeling, and hematopoiesis. The human uPA gene contains a major promoter
      region at around 2000 bp upstream from the transcription start site (+1), and a
      second regulatory region spanning nucleotides -90/+32 within the proximal
      promoter. Here, an inspection of this region revealed a novel 13-bp palindrome
      residing at position +8/+20. Interestingly, the palindrome contains the DNA
      consensus-binding hexamer for the RUNX/AML family of transcription factors that
      play a role in hematopoiesis, leukemia, and several developmental processes.
      Measuring the expression for promoter-reporter constructs after transfection
      revealed that deletion of the palindrome abrogated most of the proximal promoter
      activity in 293A cell. Additionally, electrophoretic mobility shift assays have
      shown that the palindrome could bind the RUNX1 component in nuclear extracts of
      myeloid cell lines exclusively through its RUNX motif. The palindrome was found
      in five additional human genes, two of which (MYH11 and MLLT1) have been linked
      to chromosomal rearrangements leading to leukemia. The data presented here have
      implicated, for the first time, RUNX/AML in the regulation of the uPA gene. The
      significance of the novel palindrome regarding gene regulation through the RUNX
      motif deserves further investigation.

PMID- 16102113
TI  - Translocation of GPIb and Fc receptor gamma-chain to cytoskeleton in mucetin
      activated platelets.
AB  - Recent studies have implied that GPIb-IX-V as well as functioning as an adhesion
      receptor may also induce signaling to mediate binding of platelets to damaged
      vessel wall to prevent bleeding. Reorganization of the cytoskeleton and
      redistribution of platelet structural proteins and signaling molecules are
      thought to be important in this early activation process, though the molecular
      mechanisms remain to be fully defined. In this study, we have used mucetin, a
      snake venom lectin protein that activates platelets via GPIb, to study the
      redistribution of GPIb in platelets. In unstimulated platelets, a minor portion
      of GPIb localized to Triton-insoluble cytoskeleton fractions (TIC). This portion
      increased considerably after platelet activation by mucetin. We also find
      increased contents of the FcRgamma chain in TIC. Anti-GPIb antibodies, mocarhagin
      or cytochalasin D completely inhibited the cytoskeletal translocation. In
      addition, BAPTA-AM, a cytoplasmic calcium chelator, strongly inhibited this
      process. On the other hand, inhibitors of alphaIIbbeta3, PLCgamma, PKC, tyrosine
      kinases, ADP receptor, PI3-kinase or EDTA are effective in preventing GPIb
      relocation in convulxin- but not in mucetin-activated platelets. We propose that
      cytoskeletal translocation of GPIb is upstream of alphaIIbbeta3 activation and
      cross-linking of GPIb is sufficient to induce this event in mucetin-activated
      platelets.

PMID- 16102114
TI  - Molecular study of the hematopoietic zinc finger gene in three unrelated families
      with gray platelet syndrome.
AB  - Hematopoietic zinc finger (HZF) null mice have features reminiscent of patients
      with gray platelet syndrome (GPS), a rare inherited bleeding disorder. This
      similarity has suggested that HZF deregulation might be involved in the human
      disease. The sequence of the eight exons of the HZF gene as well as the study of
      its expression in blood samples from five patients belonging to three different
      families did not reveal any modifications when compared with healthy donors. This
      study indicates that HZF is unlikely to be responsible for GPS.

PMID- 16102115
TI  - Quantitation of microparticles released from coated-platelets.
AB  - Dual agonist stimulation of platelets with thrombin and convulxin results in
      generation of coated-platelets, a sub-population of cells known formerly as COAT
      platelets (collagen and thrombin). Coated-platelets retain several procoagulant
      proteins on their surface and express phosphatidylserine (PS). In this report, we
      utilize a new methodology to demonstrate that coated-platelets also release
      microparticles. Platelets were prelabeled with 2.5 microm Bodipy-maleimide and
      then stimulated with convulxin plus thrombin. Microparticles, 0.3-0.5 microm in
      diameter, were observed by fluorescence confocal microscopy. Confocal microscopy
      was also used to demonstrate that microparticles were positive for glycoprotein
      IIb/IIIa, glycoprotein Ib, CD9, and PS, but negative for fibrinogen and
      thrombospondin. Furthermore, microparticles released from Bodipy-labeled
      platelets were observed by flow cytometry, and activation with convulxin plus
      thrombin produced 15 +/- 5 microparticles per coated-platelet. In contrast,
      platelets stimulated with thrombin or convulxin alone produced few
      microparticles. Phenylarsine oxide and diamide, both of which potentiate the
      mitochondrial permeability transition pore and coated-platelet production,
      significantly increased the number of microparticles released per coated
      platelet.

PMID- 16102116
TI  - A new signaling mechanism of hepatocyte growth factor-induced endothelial
      proliferation.
AB  - BACKGROUND: The hepatocyte growth factor (HGF) has been shown to promote
      endothelial cell proliferation. In this study, the signaling cascade responsible
      for the HGF-induced proliferation was examined. METHODS: The proliferation of
      human umbilical cord vein endothelial cells (HUCVEC) was determined using cell
      counts. Changes of the membrane potential were analyzed using the fluorescence
      dye DiBAC. Intracellular cGMP-levels were measured by means of [3H]-cGMP
      radioimmunoassay. Phosphorylation of the p42/p44 MAP-kinase (MAPK) and the
      endothelial nitric oxide synthase (eNOS) was analyzed by immunocytochemistry.
      RESULTS: A dose-dependent (1-30 ng mL(-1)) increase of HUCVEC proliferation with
      a maximum at a concentration of 15 ng mL(-1) was induced by HGF. This effect was
      significantly reduced by the addition of the K+ channel blocker iberiotoxin (100
      nmol L(-1)), eNOS inhibitor L-NMMA (300 micromol L(-1)), or the MEK inhibitor PD
      98059 (20 micromol L(-1)). A HGF-induced hyperpolarization that was blocked by
      iberiotoxin was observed. In addition, HGF-induced activation of the eNOS was
      blocked by the K+ channel inhibitor. An increase of +101% MAPK phosphorylation
      was induced by HGF, which was blocked, if the cells were treated with L-NMMA (n =
      20; P < 0.05), whereas HGF-induced phosphorylation of the eNOS was not affected
      by MEK inhibition. CONCLUSIONS: Hepatocyte growth factor modulates endothelial K+
      channels causing an activation of the eNOS; the increase of nitric oxide is
      necessary for the phosphorylation of the MAPK inducing the proliferation of
      HUCVEC.

PMID- 16102117
TI  - Collaborative study on monitoring methods to determine direct thrombin inhibitors
      lepirudin and argatroban.

PMID- 16102118
TI  - Mapping the platelet proteome: a report of the ISTH Platelet Physiology
      Subcommittee.
AB  - Proteomic technology has the potential to transform the way we analyze platelet
      biology, through the determination of platelet protein composition and its
      modification upon stimulation and with disease. We are a considerable way from
      achieving these goals, however, because of significant limitations in current
      methodology. It is therefore important to consider the extent to which these aims
      can be met and the way that proteomic data should be presented and used. These
      issues are discussed in the present paper by the Platelet Physiology Subcommittee
      of the ISTH Scientific Standardisation Committee (SSC). It is recommended that
      proteomic information be combined with data from other experimental approaches to
      establish a database on protein expression and function in platelets.

PMID- 16102119
TI  - Effects of ambient ozone on the procoagulant status and systemic inflammatory
      response.

PMID- 16102120
TI  - Exposure to diesel exhaust nanoparticles does not induce blood hypercoagulability
      in an at-risk population.

PMID- 16102121
TI  - The relationships of ABO, Lewis and Secretor blood groups with cerebral ischaemia
      of arterial origin.

PMID- 16102122
TI  - Viral respiratory tract infections increase platelet reactivity and activation:
      an explanation for the higher rates of myocardial infarction and stroke during
      viral illness.

PMID- 16102123
TI  - Strenuous sport activities involving the upper extremities increase the risk of
      venous thrombosis of the arm.

PMID- 16102124
TI  - Audit-guided action can improve the compliance with thromboembolic prophylaxis
      prescribing to hospitalized, acutely ill older adults.

PMID- 16102125
TI  - Is there a true difference in recurrence rate of deep venous thrombosis between
      men and women?

PMID- 16102126
TI  - Activation of hemostasis is associated with early cognitive decline after off
      pump coronary artery bypass surgery.

PMID- 16102127
TI  - Homocysteine and tissue factor pathway inhibitor levels in patients with Fabry's
      disease.

PMID- 16102128
TI  - Further evidence that fibrillar collagen is unable to promote platelet shape
      change and aggregation in the absence of secondary agonists.

PMID- 16102129
TI  - Long-duration therapy with low molecular weight heparin in patients with
      antiphospholipid antibody syndrome resistant to warfarin therapy.

PMID- 16102130
TI  - Effects of high plasma lipoprotein (a) levels on tissue factor pathway inhibitor
      and the protein C pathway.

PMID- 16102131
TI  - An Arab selective gradient in the distribution of factor V G1691A (Leiden),
      prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T.

PMID- 16102132
TI  - Prolonged prothrombin time is not common in bird flu infection: a summary from
      Thailand.

PMID- 16102133
TI  - The development of atypical hemolytic uremic syndrome is not influenced by
      thrombophilia susceptibility factors.

PMID- 16102134
TI  - Did Jesus Christ die of pulmonary embolism?

PMID- 16102135
TI  - Did Jesus Christ die of pulmonary embolism? A rebuttal.

PMID- 16102137
TI  - Abstracts of the 45th Annual Meeting of the Society for Psychophysiological
      Research, September 21-24, 2005, Lisbon, Portugal.

PMID- 16102138
TI  - Disruption of reproductive development in male rat offspring following in utero
      exposure to phthalate esters.
AB  - Certain Phthalate esters have been shown to produce reproductive toxicity in male
      rodents with an age dependent sensitivity in effects with foetal animals being
      more sensitive than neonates which are in turn more sensitive than pubertal and
      adult animals. While the testicular effects of phthalates in rats have been known
      for more than 30 years, recent attention has been focused on the ability of these
      agents to produce effects on reproductive development in male offspring after in
      utero exposure. These esters and in particular di-butyl, di-(2-ethylhexyl) and
      butyl benzyl phthalates have been shown to produce a syndrome of reproductive
      abnormalities characterized by malformations of the epididymis, vas deferens,
      seminal vesicles, prostate, external genitalia (hypospadias), cryptorchidism and
      testicular injury together with permanent changes (feminization) in the retention
      of nipples/areolae (sexually dimorphic structures in rodents) and
      demasculinization of the growth of the perineum resulting in a reduced anogenital
      distance (AGD). Critical to the induction of these effects is a marked reduction
      in foetal testicular testosterone production at the critical window for the
      development of the reproductive tract normally under androgen control. A second
      Leydig cell product, insl3, is also significantly down regulated and is likely
      responsible for the cryptorchidism commonly seen in these phthalate-treated
      animals. The testosterone decrease is mediated by changes in gene expression of a
      number of enzymes and transport proteins involved in normal testosterone
      biosynthesis and transport in the foetal Leydig cell. Alterations in the foetal
      seminiferous cords are also noted after in utero phthalate treatment with the
      induction of multinucleate gonocytes that contribute to lowered spermatocyte
      numbers in postnatal animals. The phthalate syndrome of effects on reproductive
      development has parallels with the reported human testicular dysgenesis syndrome,
      although no cause and effect relationship exists after exposure of humans to
      phthalate esters. However humans are exposed to and produce the critical
      phthalate metabolites that have been detected in blood of the general population,
      in children and also human amniotic fluid.

PMID- 16102140
TI  - What, may I ask is happening to nursing knowledge and professional practices?
      What is nursing thinking at this turn in human history?

PMID- 16102141
TI  - Short profile: Elaine Amella.

PMID- 16102142
TI  - Clinical caring--the diary of a nurse.
AB  - AIMS AND OBJECTIVES: The aim of this study was to explore the content of
      individual acts of nursing care and to discuss how these context-specific acts
      relate to the concept of caring. DESIGN AND METHODS: The point of departure was a
      diary kept by a nurse on an oncology ward over a period of six months.
      Hermeneutic interpretation, including content analysis of verb phrases, was
      carried out to inspire reflection and discussion rather than to generalize.
      RESULTS: The verbs that occurred in the diary text represented three categories
      of acts: physical care, speech and reflection. CONCLUSIONS AND DISCUSSION: The
      diary text expresses the carer's acts as situated in a specific space and time
      through her presence, communication and reflection. The absence of bodies in this
      text points to the discourse of nursing as subjected to dualism and to the
      medical rules of knowledge. Caring emerges as experience-near action that through
      history is connected to situated knowledges, actual discourse and universal human
      condition. Relevance to clinical practice. This study demonstrated that caring
      acts are situated and conditioned and that they should therefore be researched in
      relation to the carers' acts and thoughts. This confirms the need for cooperation
      between researchers and clinical nurses in the quest of deepening our
      understanding of caring.

PMID- 16102143
TI  - Health care worker beliefs about influenza vaccine and reasons for non
      vaccination--a cross-sectional survey.
AB  - AIMS AND OBJECTIVES: To identify reasons for poor uptake of influenza vaccine in
      healthcare workers. BACKGROUND: When influenza is circulating in the community,
      influenza vaccination of healthcare workers may reduce morbidity and sick leave
      and may also reduce mortality in older hospitalized patients. Despite this,
      vaccine uptake in healthcare workers remains low. DESIGN: Cross-sectional survey.
      METHODS: Self-completed questionnaires were distributed to 144 nurses and
      healthcare assistants in two Liverpool hospitals. RESULTS: Vaccination uptake in
      this sample was 7.6%. The main reasons given for not being vaccinated were: did
      not think it was needed (29%), not aware of the vaccine (18%) and concerned about
      side-effects (11%). The main perceived benefits of vaccination were reducing sick
      leave (44%) and personal protection against influenza (28%). CONCLUSION: In this
      study, many healthcare workers demonstrated a lack of awareness and understanding
      of the vaccine, especially in relation to its benefits and side-effects.
      Relevance to clinical practice. Vaccinating healthcare workers against influenza
      can reduce staff sickness during times of winter pressure as well as reducing
      mortality in frail, older hospitalized patients. It is therefore important that
      hospitals maximize vaccine uptake by increasing awareness and promoting the
      benefits of influenza vaccine amongst healthcare workers as well as ensuring that
      all staff have the opportunity to receive the vaccine.

PMID- 16102144
TI  - Moving from institutional dependence to entrepreneurialism. Creating and funding
      a collaborative research and practice development position.
AB  - AIMS OF THE PAPER: The paper describes the creation of, the rationale behind and
      the external funding of a collaborative research-clinical practice development
      position. The paper also demonstrates the benefits of nursing's collaboration
      with external funding bodies and the value of moving from our traditional
      position of assuming that 'the hospital' will always provide. BACKGROUND: There
      is a constant refrain that nursing must become more 'research-based' and develop
      an active research culture. In harsh financial times however, funding for
      research development is scarce. Nurses can respond to this by bemoaning the lack
      of money or by taking an entrepreneurial approach, creating innovative project
      proposals that develop new partnerships and attract external funding. DISCUSSION:
      Institutional support for clinical research is often more verbal than financial
      as most health care systems are experiencing extreme financial stringencies.
      Nurses need to reconsider the notion that every initiative must automatically be
      funded by the institution. In this paper we show how in a busy major hospital,
      clinicians and researchers collaborated to create and fund the kind of innovative
      research and practice development position that may be impossible to fund through
      existing budgets. CONCLUSION: With creativity and determination, nurses can
      challenge the orthodoxy that they are solely dependent on institutional funding.
      If there is a clear project vision, a convincing rationale, a strongly argued
      'business case' and a passionate and persistent team, then innovative new
      projects and positions can be realized. RELEVANCE TO CLINICAL PRACTICE:
      Developing clinical focused, practice based research is now a worldwide policy
      and practice imperative for nurses. Unfortunately, current levels of
      institutional funding are unlikely to support research promotion positions and
      initiatives. This paper outlines an approach to securing funding for research
      initiatives that can create exciting new positions and develop productive
      partnerships between researchers, clinicians and external agencies.

PMID- 16102145
TI  - How graduate nurses use protocols to manage patients' medications.
AB  - AIMS AND OBJECTIVES: The aim of the study was to determine how graduate nurses
      use protocols in their medication management activities. The objectives were to:
      examine the extent of adherence to various protocols in relation to medication
      activities and determine how the ward environment impacts on graduate nurses' use
      of protocols to manage patients' medications. BACKGROUND: Protocols help newly
      qualified nurses integrate new knowledge into practice and promote effective
      decision-making Design. A descriptive prospective qualitative design was used.
      Methods. Twelve graduate nurses involved in direct patient care in medical,
      surgical and specialty wards of a metropolitan teaching hospital participated in
      the study. Participant observations were conducted with the graduate nurses
      during a two-hour period when medications were being administered to patients. In
      depth interviews were conducted with each nurse immediately after observations
      and demographic data were collected on participating nurses and patients in their
      care, including all medications prescribed. Protocols associated with medication
      management activities for the clinical settings were also transcribed. RESULTS:
      Six themes were evident from the data: availability and use of protocols,
      scrutinizing patients' identity before medication administration, double-checking
      certain medications before administration, writing incident reports, following
      specific policies and timing the administration of medications. CONCLUSION:
      Graduate nurses adhered to protocols if they were perceived not to impede with
      other nursing activities. Participants were also more likely to follow protocols
      if they felt encouraged to make their own decisions and if there was a decreased
      likelihood that disciplinary action would be involved. RELEVANCE TO CLINICAL
      PRACTICE: Experienced health professionals should encourage graduate nurses to
      comply with medication protocols and to make clinically reasoned decisions about
      medication activities. By providing peer support and acting as role models,
      experienced health professionals can also demonstrate to graduate nurses how
      effective protocol use is an important component of quality patient care.

PMID- 16102146
TI  - Supporting learners in clinical practice: capacity issues.
AB  - AIM: The aim of this paper is to report a study exploring, from the perspective
      of key stakeholders (mentors of nurses, managers of nurses, and modern matrons)
      in one English acute sector hospital, how decisions are made on how many learner
      nurses can be supported in clinical practice. The objective was to identify what
      factors are taken into consideration in making these decisions. BACKGROUND:
      Supporting increasing numbers of students is a demand of current service
      provision in the English National Health Service, as part of an expansion in the
      numbers of all healthcare professionals. This is particularly the case in
      nursing, where the government announced a required increase in numbers of
      qualified nurses of 20 000. This expansion of numbers has implications for the
      quality of placement learning in clinical placements. METHODS: Data were
      collected using three focus group interviews with a total of 12 participants in
      2003/04. Recruitment was on a purposive basis. Subsequent analysis identified
      themes, which were compared across groups. A short questionnaire was also used to
      establish participants' biographical details prior to the focus groups. FINDINGS:
      Three key themes were identified: 'capacity issues', 'enhancing support in
      practice' and 'issues impacting on learning in practice'. 'Capacity issues'
      identified factors that impact on the capacity of placements to support learners.
      'Enhancing support in practice' identified necessary roles and strategies to
      enhance learning in practice. Finally, 'issues impacting on learning in practice'
      identified learner groups where support could be enhanced through structured
      management of the placement experience. CONCLUSIONS: Decisions on learner numbers
      to be supported at any one time are complex, with a multitude of dimensions.
      These include identification of types of learners and numbers of mentors
      available to support them and other operational issues. 'Educational staff' are
      needed at operational and strategic levels to support learning in practice.
      Timely and appropriate audit information to support allocation decisions and
      identify strategies to enhance the quality and support of learning in practice,
      are also required. RELEVANCE TO CLINICAL PRACTICE: Increases in learner numbers
      and National Health Service modernization have had an impact on clinical
      placements' capacity to support learning, and potentially, on learners'
      achievements in practice. Findings from this study are thus important in
      evaluating the impact of these policy initiatives.

PMID- 16102147
TI  - Living with unexplained chest pain.
AB  - AIM: The aim was to describe patients' experience of unexplained chest pain, and
      how the pain affected their everyday life. BACKGROUND: Chest pain is one of the
      most common reasons for patients to consult the emergency department. Often no
      clear ischaemic heart disease or any other somatic explanation is found.
      Exploring the pain experience and how the pain affects everyday life may provide
      insights into the patients' perspective, fill the gaps in our knowledge about
      this condition and give needed direction for nursing practice. METHOD: The study
      sample (n = 19) included 11 men and eight women admitted to the emergency
      department. An open-ended unstructured interview was conducted with each patient
      and the data were analysed using content analysis. RESULTS: The categories
      concerning pain include the informants' descriptions of several aspects of pain.
      These aspects are described in four categories and four subcategories: (i) pain
      location, (ii) pain duration with the subcategories 'periodic pain' and
      'continuous pain', (iii) pain intensity, (iv) quality of pain with the
      subcategories 'sensory aspects' and 'affective aspects' . The content of pain
      experience in everyday life was divided into four subthemes and was further
      abstracted into a theme. Four subthemes, each comprising several meaning units,
      were created and labelled: (i) fear and anxiety, (ii) feeling of uncertainty,
      (iii) feeling of stress, and (iv) loss of strength. In these descriptions, it was
      obvious that chest pain considerably disturbed and affected the informants' lives
      and an overall theme 'intrusion into the everyday life world' emerged.
      CONCLUSION: The results of this study show that unexplained chest pain intrudes
      into everyday life in a destructive manner that cannot be ignored. RELEVANCE TO
      CLINICAL PRACTICE: Patients are not receiving optimal care to relieve their pain
      and there is therefore a need for specialized nurses who can give adequate help
      and support.

PMID- 16102148
TI  - Exploring district nursing competencies in health promotion: the use of the
      Delphi technique.
AB  - AIMS AND OBJECTIVES: The research outlined in this paper aimed to establish a
      consensus view amongst primary healthcare professionals about the competencies
      that district nurses need in order to fulfil an effective role in health
      promotion. BACKGROUND: In recent years there has been a growing emphasis on
      health promotion in primary care in the United Kingdom and health promotion is
      becoming increasingly important to nurses who work in the community. However,
      consideration of the role of the district nurse in health promotion is rather
      restricted and consequently district nurses have limited access to empirical
      evidence, from which they can develop their work in health promotion. DESIGN AND
      METHODS: The Delphi technique was used for this study. Seventy-two primary
      healthcare professionals were mailed a series of three questionnaires, which
      achieved response rates of 86, 87.5 and 78.9%. RESULTS: There was a consensus
      amongst the panellists that district nurses require a range of competencies to
      engage effectively in health promotion. These were categorized to produce a
      definitive list of eight knowledge-, seven attitude- and eight skill-related
      competencies. CONCLUSIONS: For the first time, this study achieves a consensus on
      the competencies needed by district nurses to engage in health promotion.
      RELEVANCE TO CLINICAL PRACTICE: District nurses should feel encouraged to develop
      their health promotion role in light of the fact that many of the competencies
      that they require for this activity have been identified as essential for their
      day-to-day nursing practice. The research highlights the fact that new paradigm
      health promotion is a concept that has moved beyond the academic arena and is
      recognized as significant by practising health professionals.

PMID- 16102149
TI  - District nurses' involvement and attitudes to mental health problems: a three
      area cross-sectional study.
AB  - AIMS AND OBJECTIVES: The main aims of this study were to obtain information on
      the extent of staff contact and input with mental health problems and to
      determine their experience, training and attitudes to such problems. BACKGROUND:
      Historical changes and policy shifts have resulted in primary care providers
      playing an increasing role in the care of mental health problems. Such problems
      are common within community settings and a major cause of suffering and
      disability. District nurses in particular are likely to encounter a high level of
      psychological co-morbidity in their patients. Information is lacking on their
      involvement, attitudes and specific training for this area of their work. DESIGN
      AND METHODS: A cross-sectional study was conducted of the staff of district
      nursing services in three areas, Jersey (Channel Islands), Lewisham and
      Hertfordshire, using a postal questionnaire. RESULTS: Questionnaires were sent to
      331 staff; 66% responded. Community and district nurses estimated a 16%
      prevalence of mental health problems among their patients, most commonly
      dementia, depression and anxiety disorders. Staff noted participation in a wide
      range of psychological care activities, but identified a lack of training for
      this aspect of their role (three-quarter of nurses had received no such training
      during the past five years). They reported a willingness to develop their
      understanding and skills by means of educational programmes. Attitude measures
      revealed generally optimistic views concerning depression treatment, a rejection
      of deterministic attitudes about this condition and confidence in the role of
      district nursing staff in managing such problems. CONCLUSIONS: The need for
      primary care mental health training is widely noted and based upon consistent
      evidence of the limited detection and treatment of these problems. This study has
      employed quantitative methods to clarify the extent and nature of district
      nursing staff involvement in this area of practice and indicates that training
      needs are acknowledged by community nurses from geographically distinct settings.
      RELEVANCE TO CLINICAL PRACTICE: Staff are interested in developing knowledge and
      skills pertinent to the psychological problems of their patients and their views
      reveal a consensus that the most important areas for learning are recognition of
      mental disorders, anxiety management, crisis intervention and pharmacological
      treatments for depression.

PMID- 16102150
TI  - Development of an instrument measuring Chinese adolescent beliefs and attitudes
      towards substance abuse.
AB  - AIM: To develop an instrument measuring the beliefs and attitudes of Chinese
      adolescents towards substance abuse. BACKGROUND: It is documented that many
      negative consequences for youth, including physical, mental and psychosocial
      health problems are associated with substance abuse. There has led to a growing
      concern about promoting anti-drug education among health care professionals in
      Hong Kong. It is therefore important to conduct research on substance abuse to
      promote more effective anti-drug programmes for adolescents. To conduct research
      on the above aspect, valid and reliable instruments for measuring factors
      associated with drug abuse are needed. An instrument, namely the Beliefs and
      Attitudes of Substance Abuse Inventory (BASAI) was developed for the purpose of
      this study. DESIGN AND METHODS: Both qualitative and quantitative approaches to
      instrument development were adopted in the study. There were two phases to the
      study. Relevant literature and the Delphi technique were employed in the first
      phase of the study. A panel of experts was interviewed for the development of a
      pool of items for the instrument. Content analysis was used to manage the
      qualitative data obtained from the interviews. Factor analysis was used for the
      psychometric testing of the items of the BASAI. A Cronbach's alpha coefficient
      was used to test the internal consistency of the instrument. The standard error
      of the mean (SEM) was measured to further support the reliability of the BASAI.
      The results are estimates of the validity and reliability of the instrument.
      RESULTS: Three main categories and nine sub-categories were derived from the
      interview data in the first phase of the study. The overall inter-rater
      reliability of the categories was 0.89 (kappa statistics). In the second phase, a
      Content Validity Index (CVI) of 0.92 for the instrument was achieved with the
      assistance of another panel of experts. The factor structure of the instrument
      was identified by undertaking a Principal Component Analysis. Three factors were
      extracted with a total variance account of approximately 70%. Reliability was
      established with alpha = 0.82 for the entire scale and a range of 0.78-0.92
      between the sub-scales of the instrument. A small SEM of 3.21% was calculated to
      further support the reliability. CONCLUSION: A culturally sensitive instrument
      was developed with a satisfactory level of validity and reliability. Further
      research is recommended to continuously improve and refine the instrument so that
      it can be useful currently in research and/or practice. RELEVANCE TO CLINICAL
      PRACTICE: To promote the healthy development of children and adolescents, child
      health professionals need to implement effective health promotion strategies
      including anti-drug programmes. The instrument that was developed in this study
      will hopefully contribute to the development of more effective and evidence-based
      anti-drug programmes for youths.

PMID- 16102151
TI  - The impact of a nurse-led support and education programme for spouses of stroke
      patients: a randomized controlled trial.
AB  - AIMS AND OBJECTIVES: The aim of the present study was to determine the impact of
      a nurse-led support and education programme for improving the spouses' perceived
      general quality of life, life situation, general well-being and health state.
      BACKGROUND: Stroke is a disease with great consequences for the patients and
      their families. The spouses often feel obligated to care for the patient,
      providing psychological and physical support and having to cope with the
      patient's physical and cognitive impairments. This might lead to increased
      problems, as family members struggle to adapt to their new roles and
      responsibilities. DESIGN AND METHODS: Longitudinal, randomized controlled trial.
      One hundred spouses were randomly assigned to intervention or control groups, 50
      in each group. The intervention group participated in a support and education
      programme, six times during six months, led by stroke specialist nurses. Both
      groups were followed for 12 months. RESULTS: No significant differences were
      found, between intervention and control groups, over time. In the sub analyses,
      we found that the group attending 5-6 times had a significant decrease in
      negative well-being and increased quality of life over time, while the group
      attending fewer times had a significant decrease in positive well-being and
      health state, similar to the control group, which also had a significant decrease
      in negative and general well-being. CONCLUSIONS: A support and education
      programme might have a positive effect on spouses' well-being, on condition that
      they attend at least five times. RELEVANCE TO CLINICAL PRACTICE: To facilitate
      the spouses' role as informal caregivers to the stroke patients, further
      development of the support and education programme used in the present study is
      needed, including empowerment approach and implementation of coping strategies.

PMID- 16102152
TI  - Stress and coping among families of patients with traumatic brain injury: a
      review of the literature.
AB  - AIMS AND OBJECTIVES: This literature review aims to structure the available
      information on the psychological reactions of family members confronted with
      traumatic brain injury. The stress-coping theory and the systems theory provide
      the theoretical framework for this review. METHOD: Literature review. RESULTS:
      The level of stress experienced by the family members of patients who have
      traumatic brain injury is such that professional intervention is appropriate,
      even after 10-15 years. Not the severity of the injury but the nature of the
      injuries determines the level of stress. Partners experience more stress than
      parents. Children have specific difficulties. Young families with little social
      support, financial, psychiatric and/or medical problems are the most vulnerable.
      Coping with traumatic brain injury can be described in phases. The better family
      members can cope with the situation, the better the patient's recovery. There are
      functional and non-functional coping mechanisms and coping is influenced by such
      factors as gender, social and professional support and the possibility to have
      reciprocal communication or an affective relation with the patient. RELEVANCE TO
      CLINICAL PRACTICE: Support from professionals reduces the stress being
      experienced and encourages people to cope effectively. Conflicts with
      professional carers should be avoided. Every attempt should be made to develop
      models of long-term support and care that alleviate sources of burden on
      relatives. Further research is necessary to develop such models.

PMID- 16102153
TI  - To Lopez V (2005) Commentary on Lee et al. (2004).

PMID- 16102154
TI  - Commentary on Clinton M, Murrells T and Robinson S (2005) Assessing competency in
      nursing: a comparison of nurses prepared through degree and diploma programmes.
      Journal of Clinical Nursing 14, 82-94.

PMID- 16102156
TI  - To Draper P (2005) commentary on Hamilton G et Al. (2004).

PMID- 16102157
TI  - Commentary on Bash A (2004) Spirituality: the emperor's new clothes? Journal of
      Clinical Nursing 13, 11-16.

PMID- 16102160
TI  - Commentary on Farnell S, Maxwell L, Tan S, Rhodes A and Philips B (2005)
      Temperature measurement: a comparison of non-invasive methods used in adult
      critical care. Journal of Clinical Nursing 14, 632-639.

PMID- 16102162
TI  - Commentary on Nyqvist KH, Sorell A & Ewald U (2005) Litmus tests for verification
      of feeding tube locations in infants: evaluation of their clinical use. Journal
      of Clinical Nursing 14, 486-495.

PMID- 16102164
TI  - Commentary on Walsgrove H and Fulbrook P (2005) Advancing the clinical
      perspective: a practice development project to develop the nurse practitioner
      role in an acute hospital trust. Journal of Clinical Nursing 14, 444-455.

PMID- 16102166
TI  - Commentary on Pedersen PU (2005) Nutritional care: the effectiveness of actively
      involving elder patients. Journal of Clinical Nursing14, 247-255.

PMID- 16102167
TI  - Commentary on Zeitz K (2005) Nursing observations during the first 24 hours after
      a surgical procedure: what so we do? Journal of Clinical Nursing 14, 334-343.

PMID- 16102169
TI  - Genetic alteration of anxiety and stress-like behavior in mice lacking CaMKIV.
AB  - Calcium-calmodulin-dependent protein kinase IV (CaMKIV) phosphorylates the major
      transcription factor cyclic AMP-response element binding protein (CREB), which
      plays a role in emotional behavior. Here, CaMKIV knockout mice (CaMKIV(-/-)) were
      tested in a battery of stress and anxiety-related behavioral tests, to determine
      if CaMKIV plays a role in emotional behavior. CaMKIV(-/-) exhibited a decrease in
      anxiety-like behavior in both the elevated plus maze and dark-light emergence
      tests when compared to wild-type mice. Both the acoustic startle response and
      prepulse inhibition of startle were decreased with the deletion of CaMKIV. In
      addition, CaMKIV(-/-) mice displayed a lack of stress-induced analgesia following
      restraint or cold swim stress. Our results demonstrate a key role for CaMKIV in
      anxiety and stress-related behavior.

PMID- 16102170
TI  - Highly syntenic regions in the genomes of soybean, Medicago truncatula, and
      Arabidopsis thaliana.
AB  - BACKGROUND: Recent genome sequencing enables mega-base scale comparisons between
      related genomes. Comparisons between animals, plants, fungi, and bacteria
      demonstrate extensive synteny tempered by rearrangements. Within the legume plant
      family, glimpses of synteny have also been observed. Characterizing syntenic
      relationships in legumes is important in transferring knowledge from model
      legumes to crops that are important sources of protein, fixed nitrogen, and
      health-promoting compounds. RESULTS: We have uncovered two large soybean regions
      exhibiting synteny with M. truncatula and with a network of segmentally
      duplicated regions in Arabidopsis. In all, syntenic regions comprise over 500
      predicted genes spanning 3 Mb. Up to 75% of soybean genes are colinear with M.
      truncatula, including one region in which 33 of 35 soybean predicted genes with
      database support are colinear to M. truncatula. In some regions, 60% of soybean
      genes share colinearity with a network of A. thaliana duplications. One region is
      especially interesting because this 500 kbp segment of soybean is syntenic to two
      paralogous regions in M. truncatula on different chromosomes. Phylogenetic
      analysis of individual genes within these regions demonstrates that one is
      orthologous to the soybean region, with which it also shows substantially denser
      synteny and significantly lower levels of synonymous nucleotide substitutions.
      The other M. truncatula region is inferred to be paralogous, presumably resulting
      from a duplication event preceding speciation. CONCLUSION: The presence of well
      defined M. truncatula segments showing orthologous and paralogous relationships
      with soybean allows us to explore the evolution of contiguous genomic regions in
      the context of ancient genome duplication and speciation events.

PMID- 16102171
TI  - Spatiotemporal receptive field properties of epiretinally recorded spikes and
      local electroretinograms in cats.
AB  - BACKGROUND: Receptive fields of retinal neural signals of different origin can be
      determined from extracellular microelectrode recordings at the inner retinal
      surface. However, locations and types of neural processes generating the
      different signal components are difficult to separate and identify. We here
      report epiretinal receptive fields (RFs) from simultaneously recorded spikes and
      local electroretinograms (LERGs) using a semi-chronic multi-electrode in vivo
      recording technique in cats. Broadband recordings were filtered to yield LERG and
      multi unit as well as single unit spike signals. RFs were calculated from
      responses to multifocal pseudo-random spatiotemporal visual stimuli registered at
      the retinal surface by a 7-electrode array. RESULTS: LERGs exhibit spatially
      unimodal RFs always centered at the location of the electrode tip. Spike-RFs are
      either congruent with LERG-RFs (N = 26/61) or shifted distally (N = 35/61) but
      never proximally with respect to the optic disk. LERG-RFs appear at shorter
      latencies (11.9 ms +/- 0.5 ms, N = 18) than those of spikes (18.6 ms +/- 0.4 ms,
      N = 53). Furthermore, OFF-center spike-RFs precede and have shorter response rise
      times than ON-center spike-RFs. Our results indicate that displaced spike-RFs
      result from action potentials of ganglion cell axons passing the recording
      electrode en route to the optic disk while LERG-RFs are related to superimposed
      postsynaptic potentials of cells near the electrode tip. CONCLUSION: Besides
      contributing to the understanding of retinal function we demonstrate the caveats
      that come with recordings from the retinal surface, i.e., the likelihood of
      recordings from mixed sets of retinal neurons. Implications for the design of an
      epiretinal visual implant are discussed.

PMID- 16102172
TI  - Can ovarian infertility be treated with bone marrow- or ovary-derived germ cells?
AB  - A year ago, reproductive biologists and general public were astonished with
      evidence reported by Johnson et al. in Nature 428:145 that mammalian ovaries
      possess persisting large germline stem cells, which allegedly enable follicular
      renewal in adult females. Recently, the same research group declared such view
      obscure, and reported that mammalian oocytes originate from putative germ cells
      in bone marrow and are distributed by peripheral blood to the ovaries (Cell
      122:303). While neglecting available data on the germ cell origin from the
      ovarian surface epithelium (OSE) in adult mouse and human females and complexity
      of follicular renewal in humans, the authors widely extrapolated their
      observations on formation of allogeneic oocytes after bone marrow (or blood)
      transplantation in ovaries of adult mice treated with cytostatics to clinical
      implications in the public media. Yet, the resulting outcome that such allogeneic
      oocytes may enable the propagation of ovarian cycles is a poor alleviation for
      the women with ovarian infertility. Women lacking primary follicles, or carrying
      follicles with low quality eggs persisting in aging ovaries, are not concerned
      about the lack of menstrual cycles or ovarian steroids, but about virtually no
      chance of having genetically related children. Johnson et al. also reported that
      the germ cell formation in bone marrow disappears in ovariectomized mice. Such
      observation, however, raises solid doubts on the bone marrow origin of oocytes.
      Since germ cells developing from the OSE cells of adult human ovaries during
      periodical follicular renewal are known to enter blood vessels in order to enable
      formation of primary follicles at distant ovarian sites, they also contaminate
      peripheral blood and hence bone marrow. Better knowledge on the complexity of
      follicular renewal in humans and exploration of a potential of human OSE cells to
      produce new oocytes in vitro are essential for novel approaches to the autologous
      treatment of premature ovarian failure and age induced ovarian infertility.

PMID- 16102173
TI  - Implementation of a health care policy: an analysis of barriers and facilitators
      to practice change.
AB  - BACKGROUND: Governments often create policies that rely on implementation by arms
      length organizations and require practice changes on the part of different
      segments of the health care system without understanding the differences in and
      complexities of these agencies. In 2000, in response to publicity about the
      shortening length of postpartum hospital stay, the Ontario government created a
      universal program offering up to a 60-hour postpartum stay and a public health
      follow-up to mothers and newborn infants. The purpose of this paper is to examine
      how a health policy initiative was implemented in two different parts of a health
      care system and to analyze the barriers and facilitators to achieving practice
      change. METHODS: The data reported came from two studies of postpartum health and
      service use in Ontario Canada. Data were collected from newly delivered mothers
      who had uncomplicated vaginal deliveries. The study samples were drawn from the
      same five purposefully selected hospitals for both studies. Questionnaires prior
      to discharge and structured telephone interviews at 4-weeks post discharge were
      used to collect data before and after policy implementation. Qualitative data
      were collected using focus groups with hospital and community-based health care
      practitioners and administrators at each site. RESULTS: In both studies, the
      respondents reflected a population of women who experienced an "average" or non
      eventful hospital-based, singleton vaginal delivery. The findings of the second
      study demonstrated wide variance in implementation of the offer of a 60-hour stay
      among the sites and focus groups revealed that none of the hospitals acknowledged
      the 60-hour stay as an official policy. The uptake of the offer of a 60-hour stay
      was unrelated to the rate of offer. The percentage of women with a hospital stay
      of less than 25 hours and the number with the guideline that the call be within
      48 hours of hospital discharge. Public health telephone contact was high although
      variable in relation to compliance the guideline that the call be within 48 hours
      of hospital discharge. Home visits were offered at consistently high rates.
      CONCLUSION: Policy enactment is sometimes inadequate to stimulate practice
      changes in health care. Policy as a tool for practice change must thoughtfully
      address the organizational, professional, and social contexts within which the
      policy is to be implemented. These contexts can either facilitate or block
      implementation. Our examination of Ontario's universal postpartum program
      provides an example of differential implementation of a common policy intended to
      change post-natal care practices that reflects the differential influence of
      context on implementation.

PMID- 16102174
TI  - Verbal and physical violence towards hospital- and community-based physicians in
      the Negev: an observational study.
AB  - BACKGROUND: Over recent years there has been an increasing prevalence of verbal
      and physical violence in Israel, including in the work place. Physicians are
      exposed to violence in hospitals and in the community. The objective was to
      characterize acts of verbal and physical violence towards hospital- and community
      based physicians. METHODS: A convenience sample of physicians working in the
      hospital and community completed an anonymous questionnaire about their
      experience with violence. Data collection took place between November 2001 and
      July 2002. One hundred seventy seven physicians participated in the study, 95
      from the hospital and 82 from community clinics. The community sample included
      general physicians, pediatricians, specialists and residents. RESULTS: Ninety
      nine physicians (56%) reported at least one act of verbal violence and 16
      physicians (9%) reported exposure to at least one act of physical violence during
      the previous year. Fifty-one hospital physicians (53.7%) were exposed to verbal
      violence and 9 (9.5%) to physical violence. Forty-eight community physicians
      (58.5%) were exposed to verbal violence and 7 (8.5%) to physical violence.
      Seventeen community physicians (36.2%) compared to eleven hospital physicians
      (17.2%) said that the violence had a negative impact on their family and on their
      quality of life (p < 0.05). The most common causes of violence were long waiting
      time (46.2%), dissatisfaction with treatment (15.4%), and disagreement with the
      physician (10.3%). CONCLUSION: Verbal and/or physical violence against physicians
      is common in both the hospital and in community clinics. The impatience that
      accompanies waiting times may have a cultural element. Shortening waiting times
      and providing more information to patients and families could reduce the rate of
      violence, but a cultural change may also be required.

PMID- 16102175
TI  - Calibration of mass spectrometric peptide mass fingerprint data without specific
      external or internal calibrants.
AB  - BACKGROUND: Peptide Mass Fingerprinting (PMF) is a widely used mass spectrometry
      (MS) method of analysis of proteins and peptides. It relies on the comparison
      between experimentally determined and theoretical mass spectra. The PMF process
      requires calibration, usually performed with external or internal calibrants of
      known molecular masses. RESULTS: We have introduced two novel MS calibration
      methods. The first method utilises the local similarity of peptide maps generated
      after separation of complex protein samples by two-dimensional gel
      electrophoresis. It computes a multiple peak-list alignment of the data set using
      a modified Minimum Spanning Tree (MST) algorithm. The second method exploits the
      idea that hundreds of MS samples are measured in parallel on one sample support.
      It improves the calibration coefficients by applying a two-dimensional Thin Plate
      Splines (TPS) smoothing algorithm. We studied the novel calibration methods
      utilising data generated by three different MALDI-TOF-MS instruments. We
      demonstrate that a PMF data set can be calibrated without resorting to external
      or relying on widely occurring internal calibrants. The methods developed here
      were implemented in R and are part of the BioConductor package mscalib available
      from http://www.bioconductor.org. CONCLUSION: The MST calibration algorithm is
      well suited to calibrate MS spectra of protein samples resulting from two
      dimensional gel electrophoretic separation. The TPS based calibration algorithm
      might be used to correct systematic mass measurement errors observed for large MS
      sample supports. As compared to other methods, our combined MS spectra
      calibration strategy increases the peptide/protein identification rate by an
      additional 5-15%.

PMID- 16102176
TI  - Tests for the replication of an association between Egfr and natural variation in
      Drosophila melanogaster wing morphology.
AB  - BACKGROUND: Quantitative differences between individuals stem from a combination
      of genetic and environmental factors, with the heritable variation being shaped
      by evolutionary forces. Drosophila wing shape has emerged as an attractive system
      for genetic dissection of multi-dimensional traits. We utilize several
      experimental genetic methods to validation of the contribution of several
      polymorphisms in the Epidermal growth factor receptor (Egfr) gene to wing shape
      and size, that were previously mapped in populations of Drosophila melanogaster
      from North Carolina (NC) and California (CA). This re-evaluation utilized
      different genetic testcrosses to generate heterozygous individuals with a variety
      of genetic backgrounds as well as sampling of new alleles from Kenyan stocks.
      RESULTS: Only one variant, in the Egfr promoter, had replicable effects in all
      new experiments. However, expanded genotyping of the initial sample of inbred
      lines rendered the association non-significant in the CA population, while it
      persisted in the NC sample, suggesting population specific modification of the
      quantitative trait nucleotide QTN effect. CONCLUSION: Dissection of quantitative
      trait variation to the nucleotide level can identify sites with replicable
      effects as small as one percent of the segregating genetic variation. However,
      the testcross approach to validate QTNs is both labor intensive and time
      consuming, and is probably less useful than resampling of large independent sets
      of outbred individuals.

PMID- 16102177
TI  - The impact of changes to heroin supply on blood-borne virus notifications and
      injecting related harms in New South Wales, Australia.
AB  - BACKGROUND: In early 2001 Australia experienced a sudden and unexpected
      disruption to heroin availability, know as the 'heroin shortage'. This 'shortage
      has been linked to a decrease in needle and syringe output and therefore possibly
      a reduction in injecting drug use. We aimed to examine changes, if any, in blood
      borne viral infections and presentations for injecting related problems related
      to injecting drug use following the reduction heroin availability in Australia,
      in the context of widespread harm reduction measures. METHODS: Time series
      analysis of State level databases on HIV, hepatitis B, hepatitis C notifications
      and hospital and emergency department data. Examination of changes in HIV,
      hepatitis B, hepatitis C notifications and hospital and emergency department
      admissions for injection-related problems following the onset of the heroin
      shortage; non-parametric curve-fitting of number of hepatitis C notifications
      among those aged 15-19 years. RESULTS: There were no changes observed in hospital
      visits for injection-related problems. There was no change related to the onset
      heroin shortage in the number of hepatitis C notifications among persons aged 15
      19 years, but HCV notifications have subsequently decreased in this group. No
      change occurred in HIV and hepatitis B notifications. CONCLUSION: A marked
      reduction in heroin supply resulted in no increase in injection-related harm at
      the community level. However, a delayed decrease in HCV notifications among young
      people may be related. These changes occurred in a setting with widespread,
      publicly funded harm reduction initiatives.

PMID- 16102210
TI  - Anaplastic (undifferentiated) thyroid cancer: improved insight and therapeutic
      strategy into a highly aggressive disease.
AB  - BACKGROUND: This review article discusses the clinical and diagnostic
      implications of anaplastic thyroid cancer, recognizing the aggressive nature of
      the disease and extensive disease progression upon diagnosis. Standard treatment
      strategies (surgical, chemotherapy, radiation) are discussed, comparing adjuvant
      and neo-adjuvant regimens and the emergence of tumour resistance with expression
      of multidrug resistance pumps. We question the pathological evolution of
      anaplasia as a 'de novo' disease or a post malignant transformation or
      dedifferentiation and the therapeutic implications of p53 mutation. Future
      treatment options are reviewed with an emphasis on specific molecular targets
      responsible for the neoplastic phenotype. METHOD: An electronic search on Medline
      and Pubmed was performed under 'anaplastic thyroid carcinoma', 'anaplastic
      thyroid carcinogenesis', 'anaplastic thyroid carcinoma treatment reviews'.
      Relevant papers were systematically reviewed from 1965 to present.

PMID- 16102211
TI  - Negative pathology following endoscopic resection of T1a squamous carcinoma of
      the glottis.
AB  - Endoscopic CO(2) laser excision for T(1a) glottic cancer is a recognized
      treatment modality producing equivalent disease-free and voice results to
      external beam radiotherapy. On reviewing a series of 15 patients who had
      undergone endoscopic resection of a T(1a) glottic squamous cancer, it was noted
      that five patients had negative excisional pathology following the initial biopsy
      of an invasive squamous carcinoma. The histopathology of each patient's resected
      specimen was reviewed by a second pathologist who confirmed the accuracy of the
      results in all cases. We conclude that a significant number of early squamous
      carcinomas of the glottis present with very small localized, minimally invasive
      disease and that a proportion may be treated by biopsy alone.

PMID- 16102212
TI  - Pseudomonas aeruginosa lectins I and II and their interaction with human airway
      cilia.
AB  - The bacterium Pseudomonas aeruginosa (PA) produces two carbohydrate binding
      lectins, designated PA lectin-I and lectin-II (PA-IL, PA-IIL). Both lectins are
      used by the bacterium to adhere to the glycocalyx of mammalian cells. In
      addition, the lectins immobilize ciliary beat. The kinetics of ciliary beat
      inhibition by each individual lectin have been analysed; however, their joint
      action on cilia has not been reported. Here we demonstrate that PA-IL and PA-IIL
      inhibit ciliary beat in a similar time-dependent manner. If applied
      simultaneously, ciliary beat inhibition after five hours of incubation was weaker
      than if each lectin was applied separately. Thus it can be hypothesized that the
      lectins compete for the same binding site(s) of the glycocalyx. Sugar inhibition
      experiments demonstrate that D-galactose and L-fucose inhibit both lectins,
      although clear preferences of D-galactose for PA-IL and of L-fucose for PA-IIL
      exist. These interactions have to be kept in mind when designing sugar-based
      therapies.

PMID- 16102213
TI  - Effect of thermal energy produced by drilling on the facial nerve:
      histopathologic evaluation in guinea pigs.
AB  - The effect of thermal energy due to drilling around the facial nerve canal on the
      facial nerve was histopathologically evaluated in four guinea pigs. The bony
      canal of the facial nerve was drilled using a 3 mm diamond burr for one minute.
      The temperature changes on the facial nerve canal were noted before and after
      dissection. The temporal bones of the animals were histopathologically examined
      under light microscopy using haematoxylin & eosin (H&E) and solochrome cyanine
      staining for myelin, and immunohistochemical staining for neuronal nitric oxide
      synthase (nNOS). Compared to the control group, it was observed with H&E staining
      that there was oedema among the axonal fibres and with solochrome cyanine
      staining that the thickness of the myelin fibres was decreased, and that the
      severity and extent of nNOS activity was decreased in the axonal fibres. It was
      concluded that a temperature increase on the facial canal may potentially lead to
      inflammation of the nerve, and may also cause deterioration of nerve conduction
      to some extent.

PMID- 16102214
TI  - Complications of paediatric cochlear implantation: experience in Izmir.
AB  - Surgery for cochlear implantation (CI) bears the risks of complication associated
      with all major surgery, in addition to the particular risks associated with
      implanting a foreign body into the peripheral auditory system. Here we present a
      retrospective study involving 227 cochlear implant operations in 205 children to
      evaluate the rate of intra- and post-operative complications. Complications were
      defined as major complications, requiring explantation of the device or further
      operation, causing a significant medical problem, or leading to any degree of
      facial paralysis or requiring additional hospitalization for treatment; or
      defined as minor complications, namely those that settled spontaneously, with
      conservative treatment, with local care and/or with medication alone. In our
      study there were 15 (6.6 per cent) minor and 28 (12.33 per cent) major
      complications. The most frequent minor complication was dizziness and vomiting
      (3.08 per cent), followed by transient hemifacial oedema (1.76 per cent), head
      pain (1.32 per cent) and mild ataxia (0.4 per cent). The most frequent major
      complication was trauma to the device (9.69 per cent), followed by cerebrospinal
      fluid (CSF) gusher (2.2 per cent) and facial paresis (0.4 per cent). All of the
      device trauma cases were re-implanted. There were neither any life-threatening
      complications nor any facial nerve paralysis in our implanted children. This
      study confirms that CI is relatively safe and that major complications are few
      and within acceptable limits.

PMID- 16102215
TI  - Results of inlay cartilage myringoplasty in terms of closure of central tympanic
      membrane perforations.
AB  - There is a current effort to perform myringoplasty for tympanic membrane
      perforations as a day-stay procedure. In 1998, an inlay myringoplasty using
      tragal cartilage/perichondrium was described. A retrospective study was performed
      by the author to analyse the results of inlay cartilage myringoplasty, in terms
      of closure of simple perforations of the tympanic membrane. The results of a
      control group of previous cases of underlay temporalis fascia myringoplasty were
      retrieved from the hospital records. All the operations in both groups were
      performed by the same author at the same institution. The operation of inlay
      cartilage butterfly myringoplasty has been performed in 28 ears with simple
      central tympanic membrane perforations. Inconsistent results have been obtained,
      in that only 43 per cent showed closure of the perforation at the most recent
      follow-up. A control group of standard underlay temporalis fascia myringoplasty
      has been performed by the same author in 23 ears. Eighty-three per cent of the
      perforations were closed at the last follow-up. The difference is statistically
      highly significant (p < 0.01).

PMID- 16102216
TI  - Are adjuvant therapies for tonsillectomy evidence based?
AB  - Our aim was to ascertain the current practice of adjuvant therapy for
      tonsillectomy and to determine whether it is evidence based. Anonymized postal
      questionnaires were sent to all UK otolaryngology consultants registered with the
      specialty association, and a literature search was performed using relevant
      search terms in all possible combinations. Among the responders there was little
      enthusiasm for routine intra-operative local anaesthesia, post-operative topical
      benzydamine hydrochloride (Difflam) spray or post-operative antibiotics. This is
      consistent with the lack of robust evidence to support any of these practices.
      Paracetamol (acetaminophen) is prescribed by almost 90 per cent for post
      operative analgesia, and the current literature supports its efficacy and safety.
      Further, most practitioners combine paracetamol with opioids and/or non-steroidal
      anti-inflammatory drugs (NSAIDs). Evidence to support the additional use of these
      agents is, however, non-existent or limited. Some aspects of tonsillectomy care
      are uniform and evidence based. Others are heterogeneous and suffer from lack of
      adequate data in the literature.

PMID- 16102217
TI  - An audit of clinical resources available for the care of head and neck cancer
      patients in England.
AB  - OBJECTIVE: To undertake a postal survey of cancer networks to define the services
      available for the diagnosis, treatment and support of patients with head and neck
      cancer in England. FINDINGS: Thirty-four cancer networks are now responsible for
      the delivery of head and neck cancer services in England and 52 cancer units
      responded to our questionnaire. Multidisciplinary team working was evident in all
      centres. However such team working was not always fully staffed, especially in
      areas of national staff shortages such as pathology, radiology, dietetics and
      speech therapy. Rapid referral pathways were present for initial assessment of
      patients but clinically significant delays were identified in the provision of
      complex investigations, in access to intensive care beds and for oncological care
      -especially radiotherapy. CONCLUSIONS: Major changes in service configuration are
      likely to be required if the current national targets of time to diagnosis and
      treatment are to be met.

PMID- 16102218
TI  - Presurgical, ultrasound-guided anchor-wire marking of impalpable cervical lymph
      nodes.
AB  - This case illustrates the surgical use of wire localization, a well tried
      technique from a different field of surgery, in the removal of an ultrasound
      detected, impalpable deep lower cervical lymph node in a high-risk patient. A
      localization needle with an echogenic tip was placed freehand under ultrasound
      guidance, immediately before surgery. The imaging and marking of the impalpable
      cervical lymph node resulted in a precise surgical dissection and a reduction in
      operating time whilst minimizing risks to the patient and staff.

PMID- 16102219
TI  - Groningen valve change in difficult cases.
AB  - A difficult Groningen valve change is one of the problems frequently encountered
      in the post-laryngectomy patient. A safe and simple technique for this procedure
      is described.

PMID- 16102220
TI  - Reversible hearing loss associated with high-voltage electric shock.
AB  - Hearing loss associated with high-voltage electric shock is a rare entity and
      minimal information is available in the current literature about this condition.
      To our knowledge, this article represents the first case report in the literature
      of improvement in sensorineural hearing loss sustained due to a high-voltage
      electric shock. A case report of a patient who incurred various otologic
      problems, including hearing loss and tinnitus, is presented. An improvement in
      hearing loss and tinnitus was observed in the subsequent follow up after one
      month. Audiological findings and possible pathophysiology of hearing loss are
      discussed. We recommend that further studies be done to investigate the
      incidence, severity and pathophysiology of hearing loss in such cases.

PMID- 16102221
TI  - Fibre-optic intubation in oncological head and neck emergencies.
AB  - OBJECTIVE: Although fibre-optic bronchoscopic intubation is well recognized as
      the most valuable adjunct for elective management of the difficult airway its
      precise role in oncological head and neck emergencies has not been evaluated. The
      objective of this study was to evaluate the role of fibre-optic intubation in
      such emergencies. METHODS: This was a consecutive case series study by a single
      surgeon (the otolaryngologist) and anaesthetist team, taking place in a regional
      tertiary-referral head and neck surgical oncology centre. A series of 17
      consecutive oncological head and neck emergency patients underwent fibre-optic
      intubation with a Portex endotracheal tube of inner diameter > or =7 mm, with the
      aid of a 6-mm (EB-1830T2) Pentax fibre-optic video bronchoscope. The study
      assessed occurrence of: avoidance of tracheostomy in bleeding emergencies; a well
      placed, uncomplicated tracheostomy in airway obstruction; and successful
      intubation. RESULTS: Two cases were decannulated completely. All cases were
      successfully intubated and a tracheostomy was avoided in all cases in which
      emergency intubation was required and the patient was bleeding. We conclude that
      fibre-optic bronchoscopic intubation is a viable option in head and neck
      oncological emergencies due to upper airway obstruction and tumour bleeding.
      Clinical and endoscopic judgement and operator experience are the key factors
      determining success.

PMID- 16102222
TI  - Embryonal rhabdomyosarcoma of adult nasopharynx.
AB  - Adult rhabdomyosarcomas in the head and neck are extremely rare and carry a poor
      prognosis. They should be considered as a distinct clinical entity. The authors
      report a case of embryonal rhabdomyosarcoma in an adult nasopharynx treated with
      a combined modality treatment of chemotherapy and radiotherapy as per the
      European International Society of Paediatric Oncology (SIOP) MMT 89 study, group
      D. The patient responded to treatment and 10 years later, he is still alive with
      no signs of metastatic disease.

PMID- 16102223
TI  - Pott's puffy tumour caused by mucormycosis.
AB  - A case of Pott's puffy tumour in a diabetic patient with renal failure is
      reported. The patient did not respond to intravenous antibiotics and further
      investigation revealed that the patient had mucormycosis. As far as we are aware,
      this is the first case of Pott's puffy tumour due to mucormycosis to be reported
      in the literature.

PMID- 16102224
TI  - B-cell lymphoma of the larynx in a patient with rheumatoid arthritis.
AB  - We report a case of B-cell lymphoma with the larynx as the primary site of
      presentation in a rheumatoid arthritis patient previously treated with
      methotrexate. Primary non-Hodgkin's lymphoma (NHL) of the larynx is rare. There
      may be an increased risk of lymphoma in patients with rheumatoid arthritis, with
      an even higher risk in those patients treated with methotrexate. The diagnostic
      and treatment options are discussed.

PMID- 16102225
TI  - Cervical radiculopathy due to intra-arterial infusion of cisplatin.
AB  - A 55-year-old man with cervical radiculopathy (C5-C8) was referred to us
      following intra-arterial infusion of cisplatin (CDDP) because of a recurrent neck
      mass of laryngeal cancer. Three hours after the CDDP infusion, he had noticed
      general weakness of the left upper extremity and hypoaesthesia of the lateral
      side of the upper and lower arm. The next day he was diagnosed with left cervical
      radiculopathy of C5 to C8, which improved gradually and had resolved completely
      six months after the infusion. Even with proper positioning of the infusion
      catheter to minimize potential complications, for anatomical reasons there are
      always some risks of neural injury with intra-arterial infusion from branches of
      the subclavian artery. This procedure should be carefully indicated in the case
      of a large neck tumour that is perfused from the major branches of the subclavian
      artery.

PMID- 16102226
TI  - Liposarcoma of the retropharyngeal space.
AB  - Liposarcoma is a common soft tissue malignancy that occurs infrequently in the
      head and neck. Liposarcoma of the retropharynx is exceptionally rare, only four
      cases being described in the literature. We present a case in which
      retropharyngeal liposarcoma occurred in a patient who had had multiple previous
      subcutaneous lipomas excised. This paper explores this very unusual presentation
      and discusses the difficulties in the diagnosis and management of this rare
      tumour.

PMID- 16102227
TI  - Fulminant post-tonsillectomy haemorrhage caused by aberrant course of the
      external carotid artery.
AB  - Haemorrhage, throat pain and otalgia are common complications following
      tonsillectomy. Haemorrhage is rarely life-threatening but in this paper we
      describe a fulminant secondary haemorrhage due to an aberrant external carotid
      artery in an eight-year-old boy. Acute surgical intervention with ligation of the
      external carotid artery was needed to control the bleeding.

PMID- 16102228
TI  - Large B-cell non-Hodgkin's lymphoma presenting as a laryngeal cyst.
AB  - Cystic lesions of the larynx are most commonly benign. However, we report a case
      of non-Hodgkin's lymphoma (NHL) of the larynx which presented as a supraglottic
      cyst. This form of presentation has not been previously described in the medical
      literature.

PMID- 16102229
TI  - Bilateral internal jugular vein thrombosis in a child with protein S deficiency.
AB  - Internal jugular vein thrombosis is a rare but treatable disorder with most of
      the reports in the literature related to the adult population. The most common
      reported cause is iatrogenic trauma to the internal jugular vein and only a few
      cases have been reported in the paediatric population. We present a case of
      bilateral internal jugular venous thrombosis with pulmonary and cerebral
      complications in a 14-year-old girl with protein S deficiency. This problem has
      not been previously reported in the world literature.

PMID- 16102231
TI  - Functional specialization within the medial frontal gyrus for perceptual go/no-go
      decisions based on "what," "when," and "where" related information: an fMRI
      study.
AB  - Cortical systems engaged during executive and volitional functions receive and
      integrate input from multiple systems. However, these integration processes are
      not well understood. In particular, it is not known whether these input pathways
      converge or remain segregated at the executive levels of cortical information
      processing. If unilateral information streams are conserved within structures
      that serve high-level executive functions, then the functional organization
      within these structures would predictably be similarly organized. If, however,
      unilateral input information streams are integrated within executive-related
      structures, then activity patterns will not necessarily reflect lower
      organizations. In this study, subjects were imaged during the performance of a
      "perceptual go/no-go" task for which instructions were based on spatial
      ("where"), temporal ("when"), or object ("what") stimulus features known to
      engage unilateral processing streams, and the expected hemispheric biases were
      observed for early processing areas. For example, activity within the inferior
      and middle occipital gyri, and the middle temporal gyrus, during the what and
      when tasks, was biased toward the left hemisphere, and toward the right
      hemisphere during the "where" task. We discover a similar lateralization within
      the medial frontal gyrus, a region associated with high-level executive functions
      and decision-related processes. This lateralization was observed regardless of
      whether the response was executed or imagined, and was demonstrated in multiple
      sensory modalities. Although active during the go/no-go task, the cingulate gyrus
      did not show a similar lateralization. These findings further differentiate the
      organizations and functions of the medial frontal and cingulate executive
      regions, and suggest that the executive mechanisms operative within the medial
      frontal gyrus preserve fundamental aspects of input processing streams.

PMID- 16102232
TI  - Working memory maintenance contributes to long-term memory formation: neural and
      behavioral evidence.
AB  - Theories of human memory have led to conflicting views regarding the relationship
      between working memory (WM) maintenance and episodic long-term memory (LTM)
      formation. Here, we tested the prediction that WM maintenance operates in two
      stages, and that processing during the initial stage of WM maintenance promotes
      successful LTM formation. Results from a functional magnetic resonance imaging
      study showed that activity in the dorsolateral prefrontal cortex and hippocampus
      during the initial stage of WM maintenance was predictive of subsequent LTM
      performance. In a behavioral experiment, we demonstrated that interfering with
      processing during the initial stage of WM maintenance impaired LTM formation.
      These results demonstrate that processing during the initial stage of WM
      maintenance directly contributes to successful LTM formation, and that this
      effect is mediated by a network that includes the dorsolateral prefrontal cortex
      and the hippocampus.

PMID- 16102233
TI  - Rhesus monkeys behave as if they perceive the Duncker Illusion.
AB  - The visual system uses the pattern of motion on the retina to analyze the motion
      of objects in the world, and the motion of the observer him/herself.
      Distinguishing between retinal motion evoked by movement of the retina in space
      and retinal motion evoked by movement of objects in the environment is
      computationally difficult, and the human visual system frequently misinterprets
      the meaning of retinal motion. In this study, we demonstrate that the visual
      system of the Rhesus monkey also misinterprets retinal motion. We show that
      monkeys erroneously report the trajectories of pursuit targets or their own
      pursuit eye movements during an epoch of smooth pursuit across an orthogonally
      moving background. Furthermore, when they make saccades to the spatial location
      of stimuli that flashed early in an epoch of smooth pursuit or fixation, they
      make large errors that appear to take into account the erroneous smooth eye
      movement that they report in the first experiment, and not the eye movement that
      they actually make.

PMID- 16102234
TI  - Catechol O-methyltransferase Val158Met polymorphism is associated with cognitive
      performance in nondemented adults.
AB  - The catechol O-methyltransferase (COMT) gene is essential in the metabolic
      degradation of dopamine in the prefrontal cortex. In the present study, we
      examined the effect of a Val158Met polymorphism in the COMT gene on individual
      differences and changes in cognition (executive functions and visuospatial
      ability) in adulthood and old age. The participants were 292 nondemented men
      (initially aged 35-85 years) from a random sample of the population (i.e., the
      Betula study) tested at two occasions with a 5-year interval. Confirmatory factor
      analyses were used to test the underlying structure of three indicators of
      executive functions (verbal fluency, working memory, and Tower of Hanoi).
      Associations between COMT, age, executive functioning, and visuospatial (block
      design) tasks were examined using repeated-measures analyses of variance.
      Carriers of the Val allele (with higher enzyme activity) compared with carriers
      of the Met/Met genotype (with low enzyme activity) performed worse on executive
      functioning and visuospatial tasks. Individuals with the Val/Val genotype
      declined in executive functioning over the 5-year period, whereas carriers of the
      Met allele remained stable in performance. An Age x COMT interaction for
      visuospatial ability located the effect for middle-aged men only. This COMT
      polymorphism is a plausible candidate gene for executive functioning and fluid
      intelligence in nondemented middle-aged and older adults.

PMID- 16102235
TI  - The role of anterior cingulate cortex in working memory is shaped by functional
      connectivity.
AB  - The anterior cingulate (AC) cortex seems to be similarly engaged by attentional
      and memory processes. We tested the hypothesis that this common activation is
      best explained by changes in the regions interacting (functionally connected)
      with AC. Subjects were tested on two variants of a 2-back working memory task: a
      standard version with strong attentional demands, and a cued version that more
      strongly promoted memory retrieval. AC activation, measured with functional MRI,
      was found in both tasks, although more sustained in the standard condition. The
      regions functionally connected to the AC, and the relation of these activity
      patterns to memory performance, were completely different across tasks. In the
      standard task, the pattern related to a speed-accuracy tradeoff, whereas the
      connectivity pattern unique to the cued task related only to better accuracy. By
      virtue of these changing patterns of functional connectivity, the contribution of
      AC to attention- and memory-driven performance was similarly changed.

PMID- 16102236
TI  - Portraits or people? Distinct representations of face identity in the human
      visual cortex.
AB  - Humans can identify individual faces under different viewpoints, even after a
      single encounter. We determined brain regions responsible for processing face
      identity across view changes after variable delays with several intervening
      stimuli, using event-related functional magnetic resonance imaging during a long
      term repetition priming paradigm. Unfamiliar faces were presented sequentially
      either in a frontal or three-quarter view. Each face identity was repeated once
      after an unpredictable lag, with either the same or another viewpoint. Behavioral
      data showed significant priming in response time, irrespective of view changes.
      Brain imaging results revealed a reduced response in the lateral occipital and
      fusiform cortex with face repetition. Bilateral face-selective fusiform areas
      showed view-sensitive repetition effects, generalizing only from three-quarter to
      front-views. More medial regions in the left (but not in the right) fusiform
      showed repetition effects across all types of viewpoint changes. These results
      reveal that distinct regions within the fusiform cortex hold view-sensitive or
      view-invariant traces of novel faces, and that face identity is represented in a
      view-sensitive manner in the functionally defined face-selective areas of both
      hemispheres. In addition, our finding of a better generalization after exposure
      to a 3/4-view than to a front-view demonstrates for the first time a neural
      substrate in the fusiform cortex for the common recognition advantage of three
      quarter faces. This pattern provides new insights into the nature of face
      representation in the human visual system.

PMID- 16102237
TI  - Further dissociating the processes involved in recognition memory: an FMRI study.
AB  - Based on an event-related potential study by Rugg et al. [Dissociation of the
      neural correlates of implicit and explicit memory. Nature, 392, 595-598, 1998],
      we attempted to isolate the hemodynamic correlates of recollection, familiarity,
      and implicit memory within a single verbal recognition memory task using event
      related fMRI. Words were randomly cued for either deep or shallow processing, and
      then intermixed with new words for yes/no recognition. The number of studied
      words was such that, whereas most were recognized ("hits"), an appreciable number
      of shallow-studied words were not ("misses"). Comparison of deep hits versus
      shallow hits at test revealed activations in regions including the left inferior
      parietal gyrus. Comparison of shallow hits versus shallow misses revealed
      activations in regions including the bilateral intraparietal sulci, the left
      posterior middle frontal gyrus, and the left frontopolar cortex. Comparison of
      hits versus correct rejections revealed a relative deactivation in an anterior
      left medial-temporal region (most likely the perirhinal cortex). Comparison of
      shallow misses versus correct rejections did not reveal response decreases in any
      regions expected on the basis of previous imaging studies of priming. Given these
      and previous data, we associate the left inferior parietal activation with
      recollection, the left anterior medial-temporal deactivation with familiarity,
      and the intraparietal and prefrontal responses with target detection. The absence
      of differences between shallow misses and correct rejections means that the
      hemodynamic correlates of implicit memory remain unclear.

PMID- 16102238
TI  - Getting to the meaning of the regular past tense: evidence from neuropsychology.
AB  - Neuropsychological impairments of English past tense processing inform a key
      debate in cognitive neuroscience concerning the nature of mental mechanisms. Dual
      route accounts claim that regular past tense comprehension deficits reflect a
      specific impairment of morphological decomposition (e.g., jump + ed), disrupting
      the automatic comprehension of word meaning accessed via the verb stem (e.g.,
      jump). Single-mechanism accounts claim that the deficits reflect a general
      phonological impairment that affects perception of regular past tense offsets but
      which might preserve normal activation of verb semantics. We tested four patients
      with regular past tense deficits and matched controls, using a paired auditory
      semantic priming/lexical decision task with three conditions: uninflected verbs
      (hope/wish), regular past tense primes (blamed/accuse), and irregular past tense
      primes (shook/tremble). Both groups showed significant priming for verbs with
      simple morphophonology (uninflected verbs and irregular past tenses) but the
      patients showed no priming for verbs with complex morphophonology (regular past
      tenses) in contrast to controls. The findings suggest that the patients are
      delayed in activating the meaning of verbs if a regular past tense affix is
      appended, consistent with a dual-route account of their deficit.

PMID- 16102239
TI  - Selective attention and multisensory integration: multiple phases of effects on
      the evoked brain activity.
AB  - We used event-related potentials (ERPs) to evaluate the role of attention in the
      integration of visual and auditory features of multisensory objects. This was
      done by contrasting the ERPs to multisensory stimuli (AV) to the sum of the ERPs
      to the corresponding auditory-only (A) and visual-only (V) stimuli [i.e., AV vs.
      (A + V)]. V, A, and VA stimuli were presented in random order to the left and
      right hemispaces. Subjects attended to a designated side to detect infrequent
      target stimuli in either modality there. The focus of this report is on the ERPs
      to the standard (i.e., nontarget) stimuli. We used rapid variable stimulus onset
      asynchronies (350-650 msec) to mitigate anticipatory activity and included "no
      stim" trials to estimate and remove ERP overlap from residual anticipatory
      processes and from adjacent stimuli in the sequence. Spatial attention effects on
      the processing of the unisensory stimuli consisted of a modulation of visual P1
      and N1 components (at 90-130 msec and 160-200 msec, respectively) and of the
      auditory N1 and processing negativity (100-200 msec). Attended versus unattended
      multisensory ERPs elicited a combination of these effects. Multisensory
      integration effects consisted of an initial frontal positivity around 100 msec
      that was larger for attended stimuli. This was followed by three phases of centro
      medially distributed effects of integration and/or attention beginning at around
      160 msec, and peaking at 190 (scalp positivity), 250 (negativity), and 300-500
      msec (positivity) after stimulus onset. These integration effects were larger in
      amplitude for attended than for unattended stimuli, providing neural evidence
      that attention can modulate multisensory-integration processes at multiple
      stages.

PMID- 16102240
TI  - A model of prefrontal cortical mechanisms for goal-directed behavior.
AB  - Many behavioral tasks require goal-directed actions to obtain delayed reward. The
      prefrontal cortex appears to mediate many aspects of goal-directed decision
      making. This article presents a model of prefrontal cortex function emphasizing
      the influence of goal-related activity on the choice of the next motor output.
      The model can be interpreted in terms of key elements of Reinforcement Learning
      Theory. Different neocortical minicolumns represent distinct sensory input states
      and distinct motor output actions. The dynamics of each minicolumn include
      separate phases of encoding and retrieval. During encoding, strengthening of
      excitatory connections forms forward and reverse associations between each state,
      the following action, and a subsequent state, which may include reward. During
      retrieval, activity spreads from reward states throughout the network. The
      interaction of this spreading activity with a specific input state directs
      selection of the next appropriate action. Simulations demonstrate how these
      mechanisms can guide performance in a range of goal-directed tasks, and provide a
      functional framework for some of the neuronal responses previously observed in
      the medial prefrontal cortex during performance of spatial memory tasks in rats.

PMID- 16102241
TI  - Detailed exploration of face-related processing in congenital prosopagnosia: 1.
      Behavioral findings.
AB  - We show that five individuals with congenital prosopagnosia (CP) are impaired at
      face recognition and discrimination and do not exhibit the normal superiority for
      upright over inverted faces despite intact visual acuity, low-level vision and
      intelligence, and in the absence of any obvious neural concomitant.
      Interestingly, the deficit is not limited to faces: The CP individuals were also
      impaired at discriminating common objects and novel objects although to a lesser
      extent than discriminating faces. The perceptual deficit may be attributable to a
      more fundamental visual processing disorder; the CP individuals exhibited
      difficulty in deriving global configurations from simple visual stimuli, even
      with extended exposure duration and considerable perceptual support in the image.
      Deriving a global configuration from local components is more critical for faces
      than for other objects, perhaps accounting for the exaggerated deficit in face
      processing. These findings elucidate the psychological mechanisms underlying CP
      and support the link between configural and face processing.

PMID- 16102242
TI  - Detailed exploration of face-related processing in congenital prosopagnosia: 2.
      Functional neuroimaging findings.
AB  - Specific regions of the human occipito-temporal cortex are consistently activated
      in functional imaging studies of face processing. To understand the contribution
      of these regions to face processing, we examined the pattern of fMRI activation
      in four congenital prosopagnosic (CP) individuals who are markedly impaired at
      face processing despite normal vision and intelligence, and with no evidence of
      brain damage. These individuals evinced a normal pattern of fMRI activation in
      the fusiform gyrus (FFA) and in other ventral occipito-temporal areas, in
      response to faces, buildings, and other objects, shown both as line drawings in
      detection and discrimination tasks and under more naturalistic testing conditions
      when no task was required. CP individuals also showed normal adaptation levels in
      a block-design adaptation experiment and, like control subjects, exhibited
      evidence of global face representation in the FFA. The absence of a BOLD
      behavioral correlation (profound behavioral deficit, normal face-related
      activation in the ventral occipito-temporal cortex) challenges existing accounts
      of face representation, and suggests that activation in these cortical regions
      per se is not sufficient to ensure intact face processing.

PMID- 16102243
TI  - Applying activity-based costing to the nuclear medicine unit.
AB  - Previous studies have shown the feasibility of using activity-based costing (ABC)
      in hospital environments. However, many of these studies discuss the general
      applications of ABC in health-care organizations. This research explores the
      potential application of ABC to the nuclear medicine unit (NMU) at a teaching
      hospital. The finding indicates that the current cost averages 236.11 US dollars
      for all procedures, which is quite different from the costs computed by using
      ABC. The difference is most significant with positron emission tomography scan,
      463 US dollars (an increase of 96%), as well as bone scan and thyroid scan, 114
      US dollars (a decrease of 52%). The result of ABC analysis demonstrates that the
      operational time (machine time and direct labour time) and the cost of drugs have
      the most influence on cost per procedure. Clearly, to reduce the cost per
      procedure for the NMU, the reduction in operational time and cost of drugs should
      be analysed. The result also indicates that ABC can be used to improve resource
      allocation and management. It can be an important aid in making management
      decisions, particularly for improving pricing practices by making costing more
      accurate. It also facilitates the identification of underutilized resources and
      related costs, leading to cost reduction. The ABC system will also help hospitals
      control costs, improve the quality and efficiency of the care they provide, and
      manage their resources better.

PMID- 16102244
TI  - Primary health-care teams as adaptive organizations: exploring and explaining
      work variation using case studies in rural and urban Scotland.
AB  - It is acknowledged, internationally, that health-care practitioners' work differs
      between and urban areas. While several factors affect individual teams'
      activities, there is little understanding about how patterns of work evolve.
      Consideration of work in relation to local circumstances is important for
      training, devising contracts and redesigning services. Six case studies centred
      on Scottish rural and urban general practices were used to examine, in-depth, the
      activity of primary health-care teams. Quantitative workload data about patient
      contacts were collected over 24 months. Interviews and diaries revealed
      insightful qualitative data. Findings revealed that rural general practitioners
      and district nurses tended to conduct more consultations per practice patient
      compared with their urban counterparts. Conditions seen and work tasks varied
      between case study teams. Qualitative data suggested that the key reasons for
      variation were: local needs and circumstances; choices made about deployment of
      available time, team composition and the extent of access to other services.
      Primary care teams might be viewed as adaptive organization, with co-evolution of
      services produced by health professionals and local people. The study highlights
      limitations in the application of workload data and suggests that understanding
      the nature of work in relation to local circumstances is important in service
      redesign.

PMID- 16102245
TI  - The willingness to donate blood: an empirical analysis of socio-demographic and
      motivation-related determinants.
AB  - Since the willingness to donate blood is not very high among large parts of the
      population, a better understanding of the determinants for the willingness to
      donate blood is of significant importance. This article is intended to contribute
      to higher uniformity of results in the context of research on blood donation
      behaviour. Exploratory factor analysis non-parametric tests are used to
      accomplish this. Potentially important socio-demographic and motivation-related
      variables particularly affecting the willingness to donate blood are examined. As
      an addition to the existing literature, the influence of the individual
      importance structural of characteristics of blood donation facilities, such as
      the standard of the facility's medical equipment or the training of the
      facility's staff, will be tested for its effects on the willingness to donate
      blood. The analysis will also include the influence of direct or indirect
      personal involvement on the part of the respondent. The results of the study
      indicate that typical blood donors are young women or men who are studying or
      possess a higher level of education. Furthermore, potential blood donors can
      easily be attracted by pecuniary incentives and word of mouth. Unlike non-donors,
      potential blood donors are not idle, have no fear of infections due to the
      donation and want reasonable opening hours of blood donation facilities.

PMID- 16102246
TI  - Logistic analysis of veterans' eligibility-status changes.
AB  - Currently, the US Department of Veterans Affairs provides medical care to more
      than four million veterans across the nation. Given the limited resources and
      increasing demand, the US Department of Veterans Affairs Health Administration
      (VA) is required by law to ensure that veterans with similar economic status and
      eligibility priority have similar access to VA health care, regardless of where
      they reside. This study, using descriptive statistics and logistic regression
      techniques, examines the factors that affect veterans' eligibility-status
      changes. This study found that veterans' demographics are correlated with the
      likelihood of eligibility-status conversion. More importantly, this study
      concludes that eligibility-status changes have a geographic pattern. These
      findings are important and useful in planning workload, as well as improving
      equal access of health care.

PMID- 16102247
TI  - Ring fencing of elective surgery: does it affect hospital efficiency?
AB  - Ring fencing (RF) is defined as separating elective from emergency operations in
      parallel hospital production lines. This study examines the effects of RF of
      elective surgery on hospital efficiency. The analysis is performed on two levels.
      First, an intensive three-month study at the departmental level of three
      hospitals was performed. Second, a panel data analysis of the organizational
      population of Norwegian hospitals over the period from 1992 to 2000 was
      conducted, using a 'fixed effect' regression model to analyse the effect of RF on
      hospitals' cost and technical efficiency. The intensive study indicates that RF
      could have positive effects both on cost and technical efficiency under certain
      conditions of case-mix and the demand for elective surgery, while the panel
      analyses of the effects of RF in the hospital population do not produce stable
      results. We cannot conclude that RF has unconditional positive effects on
      hospitals' efficiency. However, in certain situations of case-mix and demand for
      services, RF could be a valuable tool for managers to increase hospitals'
      efficiency.

PMID- 16102248
TI  - Management support and perceived consumer satisfaction in skilled nursing
      facilities.
AB  - How managers 'manage' employees influences important firm outcomes. Heskett,
      Sasser, and Schlesinger contend that the level of internal support for service
      workers will influence consumer satisfaction. This study empirically explores how
      skilled nursing facility (SNF) managers affect consumer satisfaction by
      encouraging employee effectiveness and listening to employees to determine how to
      improve employee effectiveness. We extend previous research by proposing
      management as a form of internal support and demonstrating its relationship to
      service process integration, as a distinct form of internal support. The results
      of our individual-level investigation of 630 nursing assistants from 45 SNFs
      provide support for our two-part hypothesis. First, active management support and
      process integration, as elements of internal support, do lead to increased
      employee satisfaction and employee effectiveness. Second, the increased employee
      satisfaction and effectiveness was positively related to consumer satisfaction,
      as evaluated by the service workers. Thus, there is a positive influence of
      management's internal support of nursing assistants on perceived consumer
      satisfaction.

PMID- 16102249
TI  - Echinacea species (Echinacea angustifolia (DC.) Hell., Echinacea pallida (Nutt.)
      Nutt.,Echinacea purpurea (L.) Moench): a review of their chemistry, pharmacology
      and clinical properties.
AB  - This paper reviews the chemistry, pharmacology and clinical properties of
      Echinacea species used medicinally. The Echinacea species Echinacea angustifolia,
      Echinacea pallida and Echinacea purpurea have a long history of medicinal use for
      a variety of conditions, particularly infections, and today echinacea products
      are among the best-selling herbal preparations in several developed countries.
      Modern interest in echinacea is focused on its immunomodulatory effects,
      particularly in the prevention and treatment of upper respiratory tract
      infections. The chemistry of Echinacea species is well documented, and several
      groups of constituents, including alkamides and caffeic acid derivatives, are
      considered important for activity. There are, however, differences in the
      constituent profile of the three species. Commercial echinacea samples and
      marketed echinacea products may contain one or more of the three species, and
      analysis of samples of raw material and products has shown that some do not meet
      recognized standards for pharmaceutical quality. Evidence from preclinical
      studies supports some of the traditional and modern uses for echinacea,
      particularly the reputed immunostimulant (or immunomodulatory) properties.
      Several, but not all, clinical trials of echinacea preparations have reported
      effects superior to those of placebo in the prevention and treatment of upper
      respiratory tract infections. However, evidence of efficacy is not definitive as
      studies have included different patient groups and tested various different
      preparations and dosage regimens of echinacea. On the basis of the available
      limited safety data, echinacea appears to be well tolerated. However, further
      investigation and surveillance are required to establish the safety profiles of
      different echinacea preparations. Safety issues include the possibility of
      allergic reactions, the use of echinacea by patients with autoimmune diseases and
      the potential for echinacea preparations to interact with conventional medicines.

PMID- 16102250
TI  - Intranasal immunization using biphasic lipid vesicles as delivery systems for
      OmlA bacterial protein antigen and CpG oligonucleotides adjuvant in a mouse
      model.
AB  - The nasal mucosa is an important arm of the mucosal system since it is often the
      first point of contact for inhaled antigens. The ineffectiveness of the simple
      delivery of soluble antigens to mucosal membranes for immunization has stimulated
      extensive studies in appropriate delivery systems and adjuvants. We have
      evaluated biphasic lipid vesicles as a novel intranasal (i.n.) delivery system
      (designated as vaccine targeting adjuvant, VTA) containing bacterial antigens and
      CpG oligodeoxynucleotides (ODNs). Results show that administration of antigen and
      CpG ODNs in biphasic lipid vesicles resulted in greater induction of IgA levels
      in serum (P< 0.05) and mucosal antibody responses such as IgA in nasal secretions
      and lung (P< 0.01) after immunization with a combined subcutaneous (s.c.)/i.n. as
      compared to s.c./s.c. approach. Based on antibody responses, VTA formulations
      were found to be suitable as delivery systems for antigens and CpG ODNs by the
      intranasal route, resulting in a Th2-type of immune response, characterized by
      IgG1 and IL-4 production at the systemic level.

PMID- 16102251
TI  - Further investigations on the role of ascorbic acid in stratum corneum lipid
      models after UV exposure.
AB  - This study is the continuation of our research into vitamin C and its possible
      effects on human skin after topical administration. The effects of ascorbic acid,
      iron ions and UV irradiation on stratum corneum lipid models were investigated.
      The lipid models used were: a simple system (linolenic acid dispersion), a
      complex system (liposomes consisting of dipalmitoylphosphatidylcholine,
      cholesterol and linolenic acid) and complex systems with additionally
      incorporated ceramides (types III and IV). The lipid peroxidation was quantified
      by the thiobarbituric acid assay. A human adult low-calcium high-temperature
      (HaCaT) keratinocytes cell culture was used as a second in-vitro model. The
      amount of intracellular peroxides was determined by measuring the fluorescence
      intensity using the dihydrorhodamine 123 assay. Electron paramagnetic resonance
      spectroscopy was used to study the influence of ascorbic acid and iron ions on
      the signal intensity of 5-doxylstearic acid during UV exposure. Ascorbic acid
      showed prooxidative properties in the thiobarbituric acid assay whereas cell
      protection was measured in the HaCaT keratinocytes experiments. Electron
      paramagnetic resonance investigations revealed different extents of free radical
      production generated by iron ions, ascorbic acid and UV irradiation. In
      evaluating the results from this study new aspects of the mechanism of lipid
      damage caused by these three factors were suggested, transcending the simple
      redox behaviour of ascorbic acid.

PMID- 16102252
TI  - Explaining the phase behaviour of the pharmaceutically relevant polymers
      poly(ethylene glycol) and poly(vinyl pyrrolidone) in semi-fluorinated liquids.
AB  - Phase behaviour studies of low molecular weight poly(ethylene glycol) (denoted
      PEG 600 and PEG 1000, corresponding to molecular weights of 600 and 1000 g mol(
      1), respectively) have been carried out in 2H,3H-perfluoropentane (HPFP) with and
      without added poly(vinyl pyrrolidone). The concentration and temperature
      dependencies of their phase behaviour and the effect of moisture on these systems
      have been established. Furthermore, the solubility of PEG 600 in binary mixtures
      of HPFP and perfluoropentane (PFP), as well as HPFP and perfluorodecalin (PFD)
      have been considered at high HPFP contents. A phase separation phenomenon in
      fluorinated non-aqueous media is reported for the first time: PEG 600 and PEG
      1000 both show a lower critical solution temperature type phase separation
      boundary. The size of the PEGs was obtained from small-angle neutron scattering
      (radius of gyration) and pulsed-gradient spin-echo NMR (hydrodynamic radius)
      measurements. It is shown that polymer conformation follows a regular trend with
      solution concentration; the size increases from <10 A at 3 wt% in HPFP to 45 +/-
      2 A at 20 wt% PEG. On changing the solvent composition by substitution of HPFP by
      PFP or PFD, the size decreases, consistent with a decrease in the hydrogen
      bonding capacity of the solvent mixture. Computer modelling indicates an
      interaction between the PEG oxygen and the hydrogen of HPFP, an interaction that
      is absent for the fully fluorinated solvents. This indicates that hydrogen
      bonding is the driving force for polymer solubility in these solvents.

PMID- 16102253
TI  - Disposition of morphine in plasma and cerebrospinal fluid varies during neonatal
      development in pigs.
AB  - The pharmacological effects of morphine are mediated via the central nervous
      system (CNS) but its clearance from the CNS in neonates has not been
      investigated. We have proposed that neonatal development of the blood-brain
      barrier affected CNS clearance mechanisms and CNS exposure to morphine. Male
      piglets (n = 5) aged one, three and six weeks were given morphine sulfate (0.5 mg
      kg(-1), i.v.). Serial blood and cerebrospinal fluid (CSF) samples were withdrawn
      over 360 min after morphine administration. Morphine concentration was measured
      by radioimmunoassay. A three-compartment model was fitted to individual data.
      Estimated parameters were reported as median and range. The peak morphine
      concentrations in plasma were not significantly different in the one-, three- or
      six-week-old piglets. Plasma clearance at one week (4.5, 3.8-8.6 mL min(-1) kg(
      1)) was significantly lower than at three weeks (30.0, 19.1- 39.0 mL min(-1) kg(
      1)) and six weeks (37.0, 29.7-82.8 mL min(-1) kg(-1)). The peak morphine
      concentration in CSF at one week (59.84, 31-67 ng mL(-1)) was higher than at
      three weeks (18.8, 17.7-25 ng mL(-1)) and six weeks (24.51, 16.5-84 ng mL(-1)),
      while CSF clearance was lower at one week (1.0, 0.18-9 mL min(-1) kg(-1))
      compared with three weeks (6.2, 2.3-9.3 mL min(-1) kg(-1)) and six weeks (3.95,
      1.3-85.7 mL min(-1) kg(-1)). Apparent plasma:CSF transfer ratio at one week was
      greater than at three and six weeks. The reduced plasma and CSF morphine
      clearance in early infancy resulted in elevated systemic and central morphine
      exposure in neonatal pigs.

PMID- 16102254
TI  - Determination of intraluminal theophylline concentrations after oral intake of an
      immediate- and a slow-release dosage form.
AB  - The purpose of this study was to evaluate a protocol which enables determining
      luminal drug concentrations after oral drug administration in man. Human
      intestinal fluids were aspirated from two sampling sites (duodenum and jejunum)
      at different time points after oral intake of theophylline; an immediate- and a
      slow-release dosage form were used to demonstrate the feasibility of
      discriminating between different formulations. Osmolarity and pH of the aspirates
      were measured and theophylline concentrations were determined by HPLC-UV. After
      intake of the immediaterelease formulation of theophylline, duodenal maximum
      concentrations up to 3 mM were reached within 30 min. Theophylline appeared to be
      almost completely absorbed before it reached the second sampling site in the
      jejunum, as observed jejunal concentrations were lower than 10% of the maximal
      duodenal concentrations. These results are in agreement with fast dissolution and
      fast absorption through the intestinal mucosa, which could be expected as
      theophylline belongs to class I of the Biopharmaceutical Classification System.
      In contrast to the immediate-release formulation, administering the slow-release
      dosage form resulted in a gradual appearance of theophylline, reaching maximal
      intestinal concentrations below 300 muM. The proposed methodology can be used to
      assess luminal drug concentrations and to monitor the time- and site-dependent
      composition of intestinal fluids after intake of an oral dosage form. This
      approach may contribute to a better understanding of the behaviour of oral drug
      formulations in the gastrointestinal tract and may be exploited to further
      unravel the complexity of the gastrointestinal absorption process. In addition,
      knowledge of luminal drug concentrations may assist in the selection of drug
      concentrations applied in in-vitro permeability assays.

PMID- 16102255
TI  - Pharmacological comparison of the vasorelaxant action displayed by kaurenoic acid
      and pimaradienoic acid.
AB  - The vascular effects of two natural occurring diterpenes from the kaurane and
      pimarane classes were compared. The diterpenes ent-kaur-16-en-19-oic acid
      (kaurenoic acid; KA) and ent-pimara-8(14), 15-dien-19-oic acid (pimaradienoic
      acid; PA) were tested for their antispasmodic activity on isolated rat aorta.
      Vascular reactivity experiments, using standard muscle bath procedures, showed
      that KA and PA (both at 50 and 100 microM) inhibited phenylephrine and KCl
      induced contraction in both endothelium-intact and endothelium-denuded rat aortic
      rings, with PA being more effective than KA. These compounds also reduced CaCl(2)
      induced contraction in Ca(2+)-free solution containing KCl (30 mm). Again, PA
      produced a greater reduction in CaCl(2)-induced contraction than KA. PA (1-300
      microM) and KA (1-450 microM) concentration dependently relaxed endothelium
      denuded aortic rings pre-contracted with KCl (maximum relaxation 102.31+/-6.94%
      and 82.71+/-1.40%, respectively). Similarly, the relaxation induced by KA on
      aortic rings pre-contracted with phenylephrine (73.06+/-3.68%) was less
      pronounced than that found for PA (102.21+/-3.64%). Incubation of endothelium
      denuded rings for different periods showed that at 50 microM, KA and PA achieved
      maximum inhibitory activity on KCl-induced contraction after incubation for 60
      (53.48+/-5.83%) and 30 min (83.89+/-2.12%), respectively. At 100 microM, KA and
      PA inhibited KCl-induced contraction, with a maximum after incubation for 30 min
      (73.58+/-5.30% and 92.07+/-1.20%, respectively). The maximum inhibition induced
      by PA at both concentrations tested was greater than that induced by KA. The
      results provide evidence that structural differences between diterpenes,
      independent of the C-19 carboxylic acid site, influence selectivity for voltage
      operated Ca2+ channels and rate of equilibrium with the target site for their
      vasorelaxant action in rat aortic rings.

PMID- 16102256
TI  - Treatment of vascular smooth muscle cells with estradiol and beta-adrenergic
      agonists has an additive effect on cAMP levels, but no additive effect on
      inhibition of collagen synthesis.
AB  - Several studies have suggested that increased cell levels of cAMP result in
      decreased rates of collagen synthesis. Oestrogen treatment of vascular smooth
      muscle cells (VSMCs) has been shown to cause increased levels of cAMP and
      decreased rates of collagen synthesis. Beta-adrenergic agonists are also known to
      increase cellular levels of cAMP in VSMCs, although the effect of beta-adrenergic
      agonists on collagen synthetic rates in VSMCs is unknown. Since beta-agonists and
      oestrogens are commonly used clinical agents these studies were conducted to
      determine the potential of these agents to have an additive effect on cell cAMP
      levels and inhibition of collagen synthetic rates. When VSMCs were treated with
      both oestrogen and isoproterenol there was an additive effect on cellular cAMP
      levels although the observed decrease in collagen synthetic rates was the same as
      observed in cells treated with just oestrogen. Treatment of VSMCs with
      propranolol inhibited isoproterenol-induced changes in cAMP but had no effect on
      either oestrogen-induced increases in cAMP levels or inhibition of collagen
      synthesis. The cellular location of cAMP following beta-adrenergic agonist
      treatment was different from the distribution of cAMP in control or oestrogen
      treated VSMCs. This difference in cellular distribution of cAMP may partially
      explain the absence of collagen synthesis inhibition following beta-adrenergic
      agonist treatment of VSMCs.

PMID- 16102257
TI  - The effect of chloral hydrate on the in-vitro T3 binding to adult rat cerebral
      nuclei.
AB  - Chloral hydrate is a widely used hypnotic drug for children and animals but the
      possible interactions of its sedative action and thyroid hormones has not been
      investigated. In this study the effect of chloral hydrate on the in-vitro binding
      of triiodothyronine (T3) to cerebral nuclei of adult rats and on the thyroid
      hormones' synaptosomal and plasma availability were examined. Our results show
      that during deep anaesthesia caused by a single intraperitoneal administration of
      chloral hydrate (100 mg kg(-1)), the maximal number of nuclear thyroid hormone
      receptors (Bmax) and the equilibrium dissociation constant (Kd) were decreased.
      These changes returned to normal values when rats woke up (2(1/2)h after chloral
      hydrate administration). Plasma or synaptosomal levels of thyroid hormones were
      unaffected during chloral hydrate treatment. Our study demonstrates that the
      nuclear T3 binding in adult rat brain is affected by the sedative action of
      chloral hydrate.

PMID- 16102258
TI  - Protective effects of baicalin on oxygen/glucose deprivation- and NMDA-induced
      injuries in rat hippocampal slices.
AB  - Baicalin is a flavonoid derivative from Scutellaria baicalensis Georgi with
      various pharmacological effects. Recently, the neuroprotective effect of baicalin
      was reported. To confirm this effect and explore the possible mechanism, we have
      investigated the protective effect of baicalin on ischaemiclike or excitotoxic
      injury and the activation of protein kinase C alpha (PKC(alpha)) in rat
      hippocampal slices. In-vitro ischaemic-like injury was induced by oxygen/glucose
      deprivation (OGD) and the excitotoxic injury by N-methyl-D-aspartate (NMDA). The
      viability and swelling of the slices were detected by triphenyltetrazolium
      chloride (TTC) staining and image analysis of light transmittance (LT),
      respectively. The translocation of PKC(alpha) was measured by immunoblotting.
      Baicalin was added during both injuries. Baicalin (0.1, 1, and 10 micromol L(-1))
      concentration-dependently inhibited OGD-induced viability reduction and acute
      neuron swelling, and inhibited the increased portion of PKC(alpha) present in the
      membrane fraction over the total PKC(alpha). Baicalin ameliorated NMDA-induced
      viability reduction (not LT elevation) and inhibited the NMDA-increased membrane
      portion of PKC(alpha) at 1 micromol L(-1). We concluded that baicalin had a
      protective effect on ischaemic-like or excitotoxic injury in rat hippocampal
      slices, which might have been partly related to inhibition of PKC(alpha)
      translocation.

PMID- 16102259
TI  - Suppressive activity of epinastine hydrochloride on TARC production from human
      peripheral blood CD4+ T cells in-vitro.
AB  - Thymus- and activation-regulated chemokine (TARC) is an important molecule in the
      development and maintenance of allergic diseases. However, there is little
      information about the influence of anti-allergic agents on TARC production. The
      aim of this study is to examine the influence of epinastine hydrochloride, an H1
      receptor antagonist, on TARC production from human peripheral blood CD4+ T cells
      using an in-vitro cell culture technique. CD4+ T cells prepared from healthy
      subjects were cultured in wells coated with a combination of OKT3 and anti-CD28
      monoclonal antibody in the presence or absence of epinastine HCl for 24 h. The
      cells were also stimulated with interleukin (IL)-4 in a similar manner. Levels of
      TARC and IL-4 in culture supernatants were examined by ELISA. The addition of
      epinastine HCl exerted a dose-dependent suppressive effect on the production of
      both TARC and IL-4 from CD4+ T cells under co-stimulatory molecule stimulation.
      The minimum concentration of the agent showing a significant suppressive effect
      on TARC and IL-4 production was 5.0 microM and 2.5 microM, respectively.
      Epinastine HCl also suppressed the ability of cells to produce TARC in response
      to IL-4 stimulation, when the agent was added to cell cultures at more than 2.5
      microM. It was concluded that this inhibitory action of epinastine HCl may be
      partially responsible for epinastine's attenuating effect on allergic diseases.

PMID- 16102260
TI  - Flavonoid glycosides inhibit oral cancer cell proliferation--role of cellular
      uptake and hydrolysis to the aglycones.
AB  - Epidemiologic evidence supports the view that dietary flavonoids exert protective
      effects in oral diseases, including cancer. However, the dietary forms of
      flavonoids, the flavonoid glycosides, are thought to be inactive, thus they must
      first be hydrolysed to their active aglycones. This may occur in the saliva in
      the oral cavity. We have examined if the flavonoid glycosides directly could
      affect cell proliferation, using the human oral squamous carcinoma SCC-9 cells.
      The cellular uptake and hydrolysis of the glycosides were assessed also. The four
      flavonoid glycosides tested each behaved differently. Genistin, the 7-glucoside
      of genistein, showed clear and consistent inhibition of cell proliferation, which
      appeared to be the result of rapid cellular uptake of the glucoside and
      hydrolysis to genistein. Spiraeoside, the 4'-glucoside of quercetin, showed a
      similar inhibition of cell proliferation, which also appeared to be associated
      with its hydrolysis to quercetin. Diosmin, the 7-rutinoside of diosmetin,
      surprisingly, was more potent and effective than diosmetin. In contrast,
      quercitrin, the 3-rhamnoside of quercetin, showed no effect and only minimal
      cellular uptake and no hydrolysis. In summary, dietary flavonoid glycosides may
      exert cellular effects in the oral cavity, but this varies greatly with the
      nature of the glycoside.

PMID- 16102261
TI  - Amelioration of doxorubicin-induced myocardial oxidative stress and
      immunosuppression by grape seed proanthocyanidins in tumour-bearing mice.
AB  - We have investigated the protective effects of grape seed proanthocyanidins on
      doxorubicin-induced toxicity in tumour-bearing mice. The intraperitoneal
      administration of doxorubicin (2 mg kg(-1) every other day, cumulative dosage for
      18 mg kg(-1)) significantly inhibited the growth of sarcoma 180, and induced
      myocardial oxidative stress with decreased superoxide dismutase and glutathione
      peroxidase activity while increasing malondialdehyde formation in the heart or
      serum. Doxorubicin-induced myocardial oxidative stress also reduced lactate
      dehydrogenase and creatine kinase activity in the heart and elevated their levels
      in the serum. Doxorubicin also affected immune functions of tumour-bearing mice
      with significantly decreased interleukin-2 (IL-2) and interferon-gamma (INF
      gamma) production, and slightly decreased natural killer (NK) cell cytotoxicity,
      lymphocyte proliferation and CD4+/CD8+ ratio. It markedly increased the
      percentages of cytotoxic T cells (CD3+CD8+), helper T cells (CD3+CD4+), IL
      2R+CD4+, and IL-2R+ cells as compared with untreated tumour-bearing mice. The
      intragastric administration of proanthocyanidin (200 mg kg(-1) daily)
      significantly inhibited tumour growth, and increased NK cell cytotoxicity,
      lymphocyte proliferation, CD4+/CD8+ ratio, IL-2 and INF-gamma production.
      Moreover, proanthocyanidin strongly enhanced the anti-tumour effect of
      doxorubicin and the above immune responses, and completely eliminated myocardial
      oxidative stress induced by doxorubicin. In conclusion, intragastric
      administration of proanthocyanidin could enhance the anti-tumour activity of
      doxorubicin and ameliorate doxorubicin-induced myocardial oxidative stress and
      immunosuppression in tumour-bearing mice.

PMID- 16102262
TI  - Bronchodilatory effects of the aqueous extract of Gynostemma pentaphyllum and
      gypenosides III and VIII in anaesthetized guinea-pigs.
AB  - The bronchodilatory activity of the aqueous extract of Gynostemma pentaphyllum
      Makino leaves was investigated in anaesthetized guinea-pigs and compared with two
      of its isolated gypenosides (III and VIII). The results showed that the
      intravenous administration of the decoction of G. pentaphyllum (2.5, 5 or 10 mg
      kg(-1)) decreased bronchial resistance in basal conditions and significantly (P <
      0.01) reduced (68% inhibition) the bronchoconstrictor action of histamine.
      Furthermore, the extract antagonized (80% inhibition) the bronchoconstrictor
      response induced by the antigen in sensitized guinea-pigs. Gypenosides III (0.7
      mg kg(-1), i.v.) and VIII (0.3 mg kg(-1), i.v.) caused a similar protective
      effect in both experimental models used; however, the duration and the intensity
      of the action was less than that of the extract containing corresponding
      quantities of gypenosides III and VIII. This study confirmed the validity of the
      traditional use of this plant in the treatment of asthma and other respiratory
      disorders.

PMID- 16102263
TI  - Gastroprotective effect of Astragaloside IV: role of prostaglandins, sulfhydryls
      and nitric oxide.
AB  - This investigation evaluated the gastroprotective activity of Astragaloside IV, a
      cycloartane-type triterpene glycoside isolated from Astragalus zahlbruckneri.
      Gastric mucosal damage was induced in rats by intragastric ethanol (1 mL/rat).
      Rats treated orally with Astragaloside IV suspended in Tween 80 at 3, 10 and 30
      mg kg(-1), showed 15, 37 and 52% gastroprotection, respectively. The
      gastroprotection observed at 30 mg kg(-1) for this compound was attenuated in
      rats pretreated with N(G)-nitro-L arginine methyl ester (70 mg kg(-1), i.p), a
      nitric oxide (NO)-synthase inhibitor, suggesting that the gastroprotective
      mechanism of this glycoside involves, at least in part, the participation of NO.
      The gastroprotective effect of Astragaloside IV was not affected by the
      inhibition of prostaglandin synthesis with indometacin (10 mg kg(-1), s.c.) nor
      by the block of endogenous sulfhydryls with N-ethylmaleimide (NEM, 10 mg kg(-1),
      s.c.). Carbenoxolone was used as a gastroprotective model drug and showed a dose
      dependent gastroprotective effect (25, 43 and 88% of gastroprotection, at 3, 10
      and 30 mg kg(-1), respectively). The partial participation of prostaglandins,
      sulfhydryls and NO was observed in the gastroprotective mechanism of
      carbenoxolone.

PMID- 16102264
TI  - Modification of gamma radiation induced response of peritoneal macrophages and
      splenocytes by Hippophae rhamnoides (RH-3) in mice.
AB  - Alcoholic extract of Hippophae rhamnoides, RH-3, reported to render >80% survival
      against lethal whole body Co-60-gamma irradiation (10 Gy) in mice, was
      investigated for its immunostimulatory effects. In comparison with un-irradiated
      control, whole body irradiation did not reduce peritoneal macrophage counts at 24
      h post-irradiation. RH-3 treatment (30 mg kg(-1) body weight) alone or 30 min
      before whole-body irradiation enhanced viable counts of macrophages significantly
      (P< or =0.05) compared with both un-irradiated control and irradiated groups.
      Whole-body irradiation reduced the number of viable splenocytes significantly
      (P<0.05) compared with un-irradiated control at 24 h post-irradiation. RH-3
      treatment alone or before whole-body irradiation appreciably countered radiation
      induced decrease in splenocyte count. 3H-thymidine uptake method revealed that
      whole-body irradiation reduced splenocyte proliferation significantly (159 +/- 45
      counts min(-1)/10(6) cells; P< or =0.05) in comparison with control (607 +/- 142
      counts min(-1)) at 24 h after irradiation but RH3 treatment before irradiation
      reduced the steep decrease and maintained it as 444+/-153 counts min(-1). After
      whole-body irradiation, the ratio of spleen weight/mouse weight decreased to 1.5
      +/- 04 compared with 2.9 +/- 0.32 in un-irradiated control at 24 h post
      irradiation. Similarly, total protein content in splenocytes also decreased to 48
      +/- 6 microg/10(6) cells in comparison with 368 +/- 16 microg/10(6) cells of un
      irradiated control. RH-3 treatment before irradiation countered radiation-induced
      decrease in both spleen weight/mouse weight ratio (4.0 +/- 0.35) and total
      protein content (360 +/- 13 mug/10(6) splenocytes). In the supernatant of
      peritoneal macrophage cultures exposed to 2 Gy Co-60-gamma radiation ex-vivo, the
      total nitrite content was enhanced significantly (P<0.05) to 5.72 +/- 0.09 microM
      in comparison with un-irradiated control (1.64 +/- 0.09 microM). RH-3 treatment
      (30 microg mL(-1)) before irradiation reduced total nitrite significantly (0.93
      +/- 0.3; P< or =0.05) in comparison with irradiated control group. At 24 h after
      whole body irradiation, the CD4+/CD8+ ratio reduced to 1.5 in comparison with un
      irradiated control (1.9) but RH-3 treatment before irradiation restored the ratio
      to 2.1. These findings explicitly reveal the immunostimulatory activity of RH-3,
      which may play an important role in the manifestation of its radioprotective
      efficacy.

PMID- 16102265
TI  - Absorption characteristics of model compounds from the small intestinal serosal
      surface and a comparison with other organ surfaces.
AB  - We examined the absorption of phenolsulfonphthalein (PSP) and fluorescein
      isothiocyanate dextrans (FD-4, MW 4400; FD-10, MW 9500; FD-40, MW 40 500) as
      model compounds through the small intestinal serosal surface. After application
      to the rat small intestinal serosal surface using a cylindrical diffusion cell,
      each compound was absorbed at different rates. The absorption ratios in 6 h after
      PSP, FD-4, FD-10 and FD-40 application were calculated to be 89.2, 34.6, 14.9 and
      2.1% of dose, respectively. Elimination profiles of PSP, FD-4 and FD-10 from the
      small intestinal serosal surface obeyed first-order kinetics. Moreover, we
      calculated the apparent permeability coefficient P(app) for comparison to other
      organ surfaces. The kidney had the highest absorption efficiency, as shown by
      having more than 1.5 times significantly higher P(app) values of PSP, FD-4 and FD
      10. Similar to the other organ surfaces, a correlation was observed between the
      P(app) of the small intestine and the molecular weight of these hydrophilic
      compounds. In addition, the small intestine is likely to contribute largely to
      hydrophilic compound absorption from the peritoneal cavity, judging from
      absorption clearance, CL(a), calculated using the peritoneal organ surface area.

PMID- 16102267
TI  - Dissecting the role of cocaine- and amphetamine-regulated transcript (CART) in
      the control of appetite.
AB  - Cocaine- and amphetamine-regulated transcript (CART) codes for a neuropeptide
      system with a number of biological roles. The high conservation of CART across
      species suggests that it has an important role in mammalian physiology. CART is
      widely expressed in the central nervous system and the periphery, but is
      particularly concentrated in the hypothalamus. CART peptides, particularly CART
      (55-102), appear to have an important function in the regulation of energy
      homeostasis. This review aims to dissect the role of CART in appetite and energy
      expenditure. CART interacts with a number of central appetite circuits.
      Hypothalamic CART expression is regulated by a number of peripheral factors,
      including the adipose hormone leptin. Intracerebroventricular administration of
      CART (55-102) reduces appetite and stimulates energy expenditure. Hypothalamic
      CART may also play an orexigenic role under specific circumstances, however, as
      injection of CART (55-102) into specific hypothalamic nuclei increases food
      intake.

PMID- 16102268
TI  - Dogs really are man's best friend--canine genomics has applications in veterinary
      and human medicine!
AB  - In 2003, the US National Human Genome Research Institute (NHGRI) agreed to fund a
      project to sequence the entire genome of a boxer dog named Tasha. Although the
      USA is a country of dog lovers, with approximately 38 million households owning
      one or more dogs, why did one of the National Institutes of Health countenance
      the use of 30 m dollars for such a purpose? The answer is that the NHGRI
      recognised the value of the dog as an unrivalled model for the study of human
      disease. In this paper, the reasons why the dog is such a good model are
      examined. Examples of where the study of disease in dogs is increasing the
      understanding of the genetic basis of human disease, of the development of
      improved diagnostic assays and of the evaluation of clinical therapies are
      provided.

PMID- 16102269
TI  - The relationship between chromatin structure and transcriptional activity in
      mammalian genomes.
AB  - In cells, chromatin is folded into a 30 nm fibre. Recent genome-wide studies have
      shown that DNaseI-sensitive sites are present in both transcribed and non
      transcribed genes and are enriched in the gene-dense regions of the human genome.
      The distribution of open chromatin has also been shown to correlate with gene
      density rather than transcription. In this review it is suggested that open
      chromatin corresponds to a 30 nm fibre interspersed with discontinuities, and
      that blocks of open chromatin might facilitate gene transcription, but are
      neither necessary nor sufficient. The nature of these discontinuities is not
      known but could correspond to alterations in chromatin fibre structure caused by
      irregular nucleosome positioning, nucleosome remodelling activities, variant
      histones or the binding of specific transcription factors.

PMID- 16102270
TI  - The amazing complexity of transcription factories.
AB  - Multicellular eukaryotes orchestrate immensely complex patterns of gene
      expression in order to define numerous specialised cell types. Patterns of
      expression are regulated at the level of DNA modification, chromatin structure,
      genome architecture and nuclear organisation. Each aspect of these features of
      regulation is controlled by complex nuclear systems, and each of the systems must
      interact to define a coherent regulatory network. In proliferating cells, and
      particularly during development, patterns of gene expression must be preserved in
      cells that have active DNA repair mechanisms and efficiently duplicate both DNA
      and the associated chromatin status--the histone code. The systems that regulate
      DNA synthesis and genome stability are integrated with those that regulate the
      efficacy of RNA synthesis, such that patterns of gene expression are maintained.
      This review analyses how different experimental approaches are revealing the
      amazing complexity of the transcriptionally active compartment of mammalian
      cells. The functional implications of this complexity will be discussed.

PMID- 16102271
TI  - Recent advancements in differential proteomics based on stable isotope coding.
AB  - Stable isotope coding continues to be a powerful approach in comparative
      proteomics. This review focuses on recent developments in stable isotope coding
      based strategies targeted towards protein expression, protein interactions with
      other biomolecules, post-translational modifications and absolute quantification.
      The focus of the bulk of proteomics studies is still on protein expression. An
      important recent application of isotope coding has been in organelle proteomics.
      The review ends with the conclusion that isotope coding remains an integral part
      of quantitative proteomics. There is, however, a need to develop coding
      strategies which can differentiate changes in protein expression and post
      translational modification, address issues of protein dynamic range and
      facilitate real-time detection of proteins which show a statistically significant
      change after stimulus.

PMID- 16102272
TI  - A tiered approach to comparative genomics.
AB  - Comparative genomics has emerged as a valuable tool for locating genes,
      transcription factor motifs and other putative control regions. There are,
      however, issues that keep comparative genomics from being a straightforward
      process. These caveats fall into three categories: database, computational and
      biological. In this review paper, these caveats will be discussed and illustrated
      using related case studies. The National Center for Biotechnology Information and
      University of California Santa Cruz genome databases were used, and VISTA, LAGAN
      and zPicture were used as comparison tools. Based on these caveats, a tiered
      approach to carrying out comparative genomic studies is presented.

PMID- 16102273
TI  - Use of transgenic zebrafish reporter lines to study calcium signalling in
      development.
AB  - Calcium signals are associated with many of the events common to animal
      development. Understanding the role of these calcium signals requires the ability
      to visualise and manipulate calcium levels in the developing embryo. Recent work
      has led to the development of sensitive protein-based probes that can be used to
      generate transgenic animals for the analysis of calcium signalling in vivo. This
      paper focuses on the use of genetically encoded calcium probes to follow calcium
      signals in zebrafish. It reviews progress and speculates on the potential for use
      in the future.

PMID- 16102276
TI  - No country is an island: comment on the House of Commons report Human
      Reproductive Technologies and the Law.
AB  - In its recent report Human Reproductive Technologies and the Law, the House of
      Commons' Select Committee on Science and Technology insisted that the United
      Kingdom 'does not take a purely insular view' on sex selection but to carefully
      consider the impact on other countries before allowing changes to current
      legislation. True, no country is an island, not even the British Isles. Still,
      outlawing a harmless practice in Great Britain because of its alleged harmful
      effects in other countries is bad public policy.

PMID- 16102277
TI  - Response to 'No country is an island: comment on the House of Commons report
      Human Reproductive Technologies and the Law'.
AB  - Edgar Dahl supports sex selection, e.g. through separation of X and Y sperm or
      through PGD. It is argued in this commentary that while such sex selection would
      seem reasonable for balancing a family (wanting a daughter if one already has a
      son, or vice-versa), it is likely to lead to skewing of female-male ratios, not
      only in India where it is already as low as 0.8 in certain parts, but possibly
      also in Great Britain as male chauvinism is not a thing of the past anywhere.

PMID- 16102278
TI  - Concerns of sex selection and regulation in the report on Human Reproductive
      Technologies and the Law.
AB  - The House of Commons Science and Technology Select Committee, comprising 11
      members, reviewed human reproductive technologies and the law and presented their
      fifth report of Session 2004-05 on 28 March 2005. They felt 'it necessary to
      reconnect the Human Fertilisation and Embryology Act of 1990 with the changes in
      modern science'.

PMID- 16102279
TI  - Are we talking about the butterflies or a butterfly effect? Comment on 'No
      country is an island'.
AB  - The recent report of the House of Commons' Select Committee on Science and
      Technology (House of Commons, 2005) states that the UK should carefully consider
      the impact of sex selection on other countries before an attempt is made to
      change or modify the legislation in UK. However, controversy exists among experts
      as well as the public on whether the issue should be discussed and evaluated
      within the British norms or from a wider multi-national perspective. This
      commentary is designed to discuss the possible impact of the UK's attitude on sex
      selection on other countries.

PMID- 16102280
TI  - Three concepts of cloning in human beings.
AB  - Human cloning, organ cloning and tissue cloning are various types of cloning that
      occur at different levels with different methodologies. According to three
      standards of terminology for an embryo (fertilization through germ cells,
      development in the uterus and having the potential to produce a human life),
      tissue cloning and type I organ cloning will not produce an embryo. In contrast,
      human cloning and type II organ cloning will produce an embryo. Thus, only non
      germinal tissue cloning and type I organ cloning are beyond the ethical question
      and will not change human beings as a species. Using cloned tissues to make new
      tissues or organs is promising for the future of medicine.

PMID- 16102281
TI  - Clinical suppression of precocious puberty with cetrorelix after failed treatment
      with GnRH agonist in a girl with gonadotrophin-independent precocious puberty.
AB  - This report presents the case of a 7-year-old girl with gonadotrophin-independent
      precocious puberty treated with cetrorelix [gonadotrophin-releasing hormone
      (GnRH) antagonist] after poor response to GnRH agonist therapy was observed in
      the endocrinology outpatient clinic. Uterine and ovarian morphology returned to
      within the normal prepubertal range after GnRH antagonist was injected
      subcutaneously. Vaginal bleeding stopped completely. The effects of GnRH
      antagonist treatment were comparable to those of GnRH agonist. The potential
      advantage of GnRH antagonists would be a clinically significant direct effect on
      the ovary, if it exists, and GnRH antagonists should be available for use in such
      children.

PMID- 16102282
TI  - Embryo quality based on ovulation induction: defining the differences.
AB  - Patients undergoing IVF, with or without intracytoplasmic sperm injection, were
      treated with either recombinant human FSH or urine-derived FSH. Response to
      ovarian stimulation was monitored by ultrasound examinations and measurement of
      serum oestradiol concentrations. To define any differences in embryo quality and
      hence assisted reproductive technology success rates, a retrospective analysis of
      811 recombinant FSH versus 555 urinary FSH cycles was undertaken. Embryo quality
      was assessed as embryo cell number and degree of fragmentation. Implantation and
      ongoing pregnancy rates were also compared. Use of recombinant FSH resulted in a
      higher percentage of mature oocytes, improved embryo cleavage, with more embryos
      available for freezing and higher implantation rates compared with urinary FSH.
      Oocyte and embryo quality were superior when recombinant FSH was used for ovarian
      stimulation compared with urinary FSH.

PMID- 16102283
TI  - Economic evaluation of the administration of follitropin-beta with a pen device.
AB  - Previous studies suggest that administration of follitropin-beta with a pen
      device (Puregon Pen(R)) is more convenient, less painful and 16-18% more
      efficient. The aim of this study was to perform an economic evaluation of the
      administration of follitropin-beta by this pen device against follitropin-alpha
      by multidose and highly purified (HP) HMG by conventional syringe in IVF
      treatment by comparing the process utilities and the costs for the Dutch setting.
      Conjoint analysis assessed the process utilities for the three administration
      modes on a scale from 0 to 1. A decision analytic model estimated the costs of an
      average IVF cycle from a societal perspective. Patients estimated the process
      utility at 0.96 for the pen, 0.53 for the multidose and 0.36 for the conventional
      syringe. Additional costs were estimated at 0 Euros and 194 Euros, comparing the
      pen with multidose or conventional methods respectively. Assuming a 16%
      efficiency gain of the pen, costs ranged from Euros-135 (savings) to 60 Euros
      (extra costs). In conclusion, patients perceive sufficient benefits to the pen
      device to choose it over other dosing methods. Dominance of the pen device over
      the multidose method was shown. Compared with the conventional administration
      method, the added value of the pen device was 2.7 (0.96/0.36) times higher.

PMID- 16102284
TI  - Polar body morphology and spindle imaging as predictors of oocyte quality.
AB  - It has been suggested that first polar body (PBI) morphology reflects oocyte
      competence. Oocytes with an intact normal-sized PBI have been described as
      generating better day 2 embryos, higher blastocyst yield, and increased pregnancy
      and implantation rates. In other studies, PBI morphology was found to be
      unrelated to fertilization rate, embryo quality, and blastocyst formation. In a
      prospective analysis, the predictive value of the PBI was investigated by
      comparing the development of oocytes retrieved from intracytoplasmic sperm
      injection patients and displaying different PBI morphology, classified according
      to the following characteristics: normal size and smooth surface (I), fragmented
      (II), rough surface (III), or large size (IV). Fertilization rates were 59, 57,
      64 and 60% respectively. No significant differences were found between the
      various groups. The proportions of high quality (grade A) day 2 embryos were also
      comparable among groups I-III (14, 12 and 17% respectively), while the low number
      of grade A embryos in group IV (two embryos) did not allow comparison with the
      other classes. These data do not suggest that PBI selection can contribute to
      identification of embryos with high developmental ability. In order to establish
      alternative criteria for oocyte selection, a metaphase II (MII) spindle analysis
      was also conducted via Polscope. In oocytes of patients of different age, spindle
      retardance (which reflects the high order and density of microtubules) was
      compared with parameters of embryo development. In aged patients, a trend was
      observed between low retardance and poor embryo quality, although in general the
      association between retardance and oocyte developmental performance did not reach
      statistical significance.

PMID- 16102286
TI  - Microtubule turnover in ooplasm biopsy reflects ageing phenomena in the parent
      oocyte.
AB  - Oviductal oocytes retrieved from superovulated B6D2F1 mice at 13.5, 16 and 19 h
      after human chorionic gonadotrophin (HCG) (groups A, B and C respectively, n =
      382) were micromanipulated to obtain 12-20 mum sized ooplasm biopsy fragments.
      Experiments were divided into three sets. Ooplasmic microtubule dynamics were
      studied in ooplasm biopsy specimens and parent oocytes (set 1) and ooplasm biopsy
      specimens (set 2), whilst zona pellucida dissolution time, cortical granule loss
      and spindle/chromatin morphology using confocal microscopy were also studied in
      parent oocytes (set 2). Oocytes withstood oocyte biopsy with a high survival rate
      (98.2%) and the biopsied oocytes underwent successful fertilization and
      development (set 3). An absolute one-to-one correlation was seen between the
      oocyte biopsy specimens and the parent oocytes in terms of ooplasmic microtubule
      dynamics (set 1), and increased ooplasmic microtubule dynamics in oocyte biopsy
      specimens paralleled ageing phenomena in the parent oocytes (set 2). Zona
      pellucida dissolution time was significantly lower in parent oocytes from group A
      versus groups B (P = 0.032), and C (P < 0.001). (Groups A, B, C include minimal,
      moderate, increased ooplasmic microtubule dynamics in oocyte biopsy specimens
      respectively.) Oocyte cortical granule loss and spindle/chromatin abnormalities
      were mainly seen in group C (P < 0.001). Oocyte biopsy can thus be applied to
      judge age-related changes in the parent oocytes.

PMID- 16102287
TI  - Vitrification demonstrates significant improvement versus slow freezing of human
      blastocysts.
AB  - Blastocyst culture has reduced the number of embryos transferred per cycle,
      whilst simultaneously creating new quandaries regarding supernumerary blastocyst
      cryopreservation. This retrospective study was undertaken to compare a slow
      freezing protocol to a vitrification protocol for cryopreservation of day 5 and
      day 6 human blastocysts. To demonstrate this, the survival, implantation rate and
      pregnancy rates were compared after thawing, assessment and embryo transfer of 86
      consecutive day 5 and day 6 thawed blastocyst transfer cycles from January 1,
      2002 to December 31, 2003. Seventy-one day 5 slow-frozen (SF) blastocysts were
      thawed and 59 embryos survived the thawing (83.1%). An average of 2.5 SF
      blastocysts was replaced per embryo transfer, resulting in a pregnancy rate of
      16.7% (4/24). Concurrently, 41 vitrified (VIT) blastocysts were thawed and all 41
      survived the thawing process (100%). An average of 2.0 VIT blastocysts was
      replaced per embryo transfer, resulting in a pregnancy rate of 50% (10/20).
      Survival, pregnancy and implantation rates of day 5 VIT blastocysts have
      significantly increased (P < 0.01, P < 0.02 and P < 0.01 respectively) over day 5
      SF blastocysts. A similar trend was observed with day 6 blastocysts.

PMID- 16102288
TI  - Influence of embryonic conditioned media upon the endometrial beta-adrenergic
      receptor.
AB  - The main objective of this study was to evaluate the influence of the products
      secreted by the human embryo upon the three subtypes of beta-AR (beta1, beta2,
      beta3). Cell cultures were developed using endometrial biopsies, taken on day 7
      after ovulation, from four healthy women <35 years of age, with regular cycles
      and infertility due only to male factors. Embryos from women with a normal
      uterine cavity and endometrial lining were incubated until they reached the 4
      cell stage, before being transferred to their mother's uterus. Culture media for
      embryo incubation were derived from two groups: (i) embryos that achieved
      pregnancy, (ii) embryos which failed to implant. Control and experimental
      endometrial cell culture plates were treated with the two embryo culture media,
      with or without 10(-9) mol/l oestradiol and 10(-7) mol/l progesterone for 48 h.
      Expression of the three subtypes of beta-AR was assessed by RT-PCR. Beta1-AR was
      expressed in both control and experimental plates; beta2-AR was expressed only in
      plates incubated with embryonic culture media of embryos which achieved
      pregnancy, in both hormonal conditions, with or without oestradiol and
      progesterone. Beta3-AR was not expressed in any condition. Thus secretory
      products of human embryos may influence gene expression of beta2-AR
      concentrations in the human endometrium, and this subtype of beta-AR may be
      involved in implantation.

PMID- 16102290
TI  - Outcome of assisted reproductive technologies after different embryo transfer
      strategies.
AB  - The outcomes of 1028 assisted reproductive technology cycles were studied
      retrospectively, considering two different periods of embryo transfer. In the
      first period, 262 cycles in women < 36 years old were studied, in which three
      embryos were transferred, followed by 157 cycles in women > or = 36 years, in
      which four embryos were transferred. In the second period, 332 cycles were
      evaluated in women < 36 years and 277 cycles in women > or = 36 years old,
      reducing the number of embryos transferred to two and three respectively. Embryos
      were only scored morphologically, and the best embryos were chosen for transfer.
      In the first period, in women < 36 years old, a clinical pregnancy rate of 55.7%
      was achieved, compared with 42.5% in the second period (P < 0.01). In women > or
      = 36 years old, the first period of embryo transfer showed a clinical pregnancy
      rate of 39.5%, compared with 28.5% in the second period (P < 0.01). The number of
      twin pregnancies in the three groups of patients in whom one to four embryos were
      transferred was not significantly different (24.2, 28.4, 24.8%). It is concluded
      that even with the biases induced by a retrospective study, the reduction in the
      number of embryos transferred, from three to two in women < 36 years of age, and
      from four to three in women > or = 36 years of age, without any selection other
      than pre-transfer morphological score, adversely affects the outcome of
      treatment, without a significant reduction in twin gestation rate. Other
      strategies are to be implemented in gametes and embryo selection, and patients
      must be aware that, even with a reduction in pregnancy rate, the goal is to
      achieve a high cumulative pregnancy rate, reducing the complications induced by
      multiple pregnancies.

PMID- 16102292
TI  - Does intravaginal probiotic supplementation increase the pregnancy rate in IVF
      embryo transfer cycles?
AB  - This study investigated the effect of intravaginal administration of probiotics
      immediately after oocyte retrieval on vaginal colonization and outcome of the IVF
      embryo transfer cycle. One hundred and seventeen women who underwent ovarian
      stimulation and IVF were randomized immediately after oocyte retrieval into two
      groups: those who received intravaginal probiotics (study group, n = 50) and
      those who did not (control group, n = 67). Vaginal colonization with lactobacilli
      and pregnancy rate were compared between the two groups. No significant between
      group differences were observed in patient age, oestrogen and progesterone
      concentrations on day of human chorionic gonadotrophin administration, number of
      oocytes retrieved, fertilization rate, number of embryos transferred, or
      pregnancy rate. The presence of lactobacilli in the vagina during oocyte
      retrieval or embryo transfer did not improve the pregnancy rate. Furthermore,
      intravaginal administration of lactobacilli following oocyte retrieval did not
      affect the prevalence of lactobacilli during embryo transfer, or the pregnancy
      rate. Intravaginal probiotic supplementation immediately after oocyte retrieval
      has no effect on vaginal colonization or pregnancy rate in IVF cycles.

PMID- 16102293
TI  - Obstetric and perinatal outcome of 1655 ICSI and 3974 IVF singleton and 1102 ICSI
      and 2901 IVF twin births: a comparative analysis.
AB  - A total of 3974 IVF and 1655 ICSI singleton births and 2901 IVF and 1102 ICSI
      twin births were evaluated. Pregnancies after both fresh and frozen transfers
      were included. IVF and ICSI singleton pregnancies were very similar for most
      obstetric and perinatal variables. The only significant difference was a higher
      risk for prematurity (< 37 weeks of amenorrhoea) in IVF pregnancies compared with
      ICSI pregnancies (12.4 versus 9.2%, OR = 1.39, 95% CI = 1.15-1.70). For twin
      pregnancies, differences were not statistically different except for a higher
      incidence of stillbirths in the ICSI group (2.08 versus 1.03%, OR = 2.04, 95% CI
      = 1.14-3.64). Intrauterine growth retardation with or without pregnancy-induced
      hypertension was observed more often in the ICSI group. Regression analysis of
      the data with correction for parity and female age showed similar results for
      twins. For singletons, this analysis showed similar results with the exception of
      low birth weight babies (< 2500 g), which were also observed more often in IVF
      pregnancies (9.6 versus 7.9%, OR = 0.79, CI = 0.65-0.98, P = 0.03). This large
      case-comparative retrospective analysis showed that the obstetric outcome and
      perinatal health of IVF and ICSI pregnancies is comparable.

PMID- 16102295
TI  - Does hormone replacement therapy prevent epithelial ovarian cancer?
AB  - Two much-debated hypotheses regarding the aetiology of epithelial ovarian cancer
      (EOC) are incessant ovulation and gonadotrophin stimulation. A significant
      inverse correlation is found between the risk of EOC and number of pregnancies,
      duration of oral contraceptive use (about 10% risk reduction per year) and
      duration of breastfeeding. Whereas ovulation in the 20-29 year age group was
      associated with a 20% increase in risk for each year of ovulation, maximum
      protective effect was noticed in late childbirth (>35 years). Although both in
      vitro and in-vivo studies showed that gonadotrophins may initiate and stimulate
      the growth of EOC, it is not known whether gonadotrophins promote EOC. FSH and LH
      receptors have been detected by ligand-binding assay and by reverse transcriptase
      polymerase chain reaction in ovarian surface epithelium (OSE) and in malignant
      epithelial ovarian tissue. Key aetiological events for this cancer may occur in
      the premenopausal period. Although hormone replacement therapy (HRT) can lower
      FSH and LH concentrations substantially, it cannot reduce EOC. The ideal time of
      ovulation and/or gonadotrophin suppression for prevention of EOC, and why oral
      contraceptives (OC) can but HRT cannot reduce EOC effectively, are unknown.
      Various growth-related genes, factors, adhesion molecules and angiogenic factors
      are present in OSE. Pituitary ovarian axis hormones seem to maintain a delicate
      balance towards growth control whilst the resultant chain of abnormal growth
      promoting events occur at cellular level. Reports regarding the relation of
      exogenous and endogenous hormones, especially oestrogen, and post-menopausal EOC
      are reviewed.

PMID- 16102296
TI  - Novel trends in follicular development, atresia and corpus luteum regression: a
      role for apoptosis.
AB  - During ovarian follicular development in humans, only a limited number of
      follicles mature and ovulate. The vast majority of follicles stop developing
      after the formation of an antrum and then undergo atresia. The few that are
      selected to become ovulatory follicles are transformed into corpora lutea
      following ovulation. The lifespan of the corpus luteum is also limited. In each
      oestrus/menstrual cycle, corpora lutea regress and are eliminated by a progress
      called luteolysis. During atresia and luteolysis, granulosa and lutein cells
      undergo apoptosis. It is believed that there are many signal transduction
      pathways that control apoptosis in order to suppress full maturation of too many
      follicles and to protect the dominant follicle from the apoptotic process prior
      the ovulation. Such interplay between different factors, some of them produced in
      the ovary, may modulate apoptosis of corpus luteum cells, in order to preserve
      the function of the corpus luteum during pregnancy or to eliminate the old
      corpora lutea of the previous cycle. The present review reports a number of
      factors that regulate follicular atresia and corpus luteum regression, via
      apoptotic pathways. Elucidation of apoptotic mechanisms may lead to prevention of
      female infertility or other pathological conditions.

PMID- 16102297
TI  - Genetics of polarity in mammalian embryos.
AB  - This brief review is devoted to the genetic control of polarity and embryonic
      axes in preimplantation mammalian embryos. Discussion is related to their
      formation, the considerable variations in gene activity in these early phases of
      development, and the influence of timers over polarities and related aspects of
      development. Modern genetic analyses assess vast numbers of genes in outline, and
      the actions of individual genes in detail. These factors operate within a mixture
      of inherited maternal controls, gene silencing, bouts of transcription and the
      actions of mini RNA in controlling gene expression. Within this context, maternal
      factors regulate the planes of early cleavage divisions and unevenly distribute
      animal and vegetal characteristics to successive blastomeres by the 4-cell stage.
      This varied inheritance confers varying combinations of animal and vegetal
      cytoplasm to single blastomeres in many human 4-cell embryos. The blastomere
      inheriting animal cytoplasm only may be the trophectodermal stem cell, that with
      vegetal cytoplasm may be the germline precursor, and the two with full polarity
      may produce inner cell mass. Some implications of these findings are considered.

PMID- 16102298
TI  - Consistency of gonadotrophin products.

PMID- 16102299
TI  - Consistency of gonadotrophin products.

PMID- 16102301
TI  - Ancient myths and avian pestilence.

PMID- 16102302
TI  - Epidemiology and transmission dynamics of West Nile virus disease.
AB  - From 1937 until 1999, West Nile virus (WNV) garnered scant medical attention as
      the cause of febrile illness and sporadic encephalitis in parts of Africa, Asia,
      and Europe. After the surprising detection of WNV in New York City in 1999, the
      virus has spread dramatically westward across the United States, southward into
      Central America and the Caribbean, and northward into Canada, resulting in the
      largest epidemics of neuroinvasive WNV disease ever reported. From 1999 to 2004,
      >7,000 neuroinvasive WNV disease cases were reported in the United States. In
      2002, WNV transmission through blood transfusion and organ transplantation was
      described for the first time, intrauterine transmission was first documented, and
      possible transmission through breastfeeding was reported. This review highlights
      new information regarding the epidemiology and dynamics of WNV transmission,
      providing a new platform for further research into preventing and controlling WNV
      disease.

PMID- 16102303
TI  - Virology, pathology, and clinical manifestations of West Nile virus disease.
AB  - West Nile virus (WNV) causes epidemics of febrile illness, meningitis,
      encephalitis, and flaccid paralysis. Since it was first detected in New York City
      in 1999, and through 2004, >16,000 WNV disease cases have been reported in the
      United States. Over the past 5 years, research on WNV disease has expanded
      rapidly. This review highlights new information regarding the virology, clinical
      manifestations, and pathology of WNV disease, which will provide a new platform
      for further research into diagnosis, treatment, and possible prevention of WNV
      through vaccination.

PMID- 16102304
TI  - Laboratory exposures to brucellae and implications for bioterrorism.
AB  - Brucellae are class 3 organisms and potential agents of bioterrorism. Because of
      effective public health measures, brucellosis has become a rare disease in
      industrialized countries, and clinical microbiology laboratories are frequently
      unfamiliar with the genus. A low index of suspicion by physicians or failure to
      notify the laboratory, equivocal Gram-stain results, misidentification of the
      organism by commercial systems, unsafe laboratory practices, and laboratory
      accidents have been responsible for numerous cases of exposure to the organism
      and laboratory-acquired disease in recent years. Discovery of a laboratory
      exposure to brucellae should prompt an exhaustive investigation of the event and
      its circumstances, definition of the population at risk, enforcement of safe
      laboratory practices, and antimicrobial drug prophylaxis for exposed persons.
      Inadvertent exposures to brucellae in the clinical laboratory indicate a
      widespread lack of preparedness to cope with eventual biologic threats involving
      use of the organism.

PMID- 16102305
TI  - Influenza A (H3N2) outbreak, Nepal.
AB  - In July 2004, an outbreak of influenza A (H3N2) was detected at 3 Bhutanese
      refugee camps in southeastern Nepal. Hemagglutination inhibition showed that
      approximately 40% of the viruses from this outbreak were antigenically distinct
      from the A/Wyoming/3/03 vaccine strain. Four amino acid differences were observed
      in most of the 26 isolates compared with the A/Wyoming/3/2003 vaccine strain. All
      4 substitutions are located within or adjacent to known antibody-binding sites.
      Several isolates showed a lysine-to-asparagine substitution at position 145
      (K145N) in the hemagglutinin molecule, which may be noteworthy since position 145
      is located within a glycosylation site and adjacent to an antibody-binding site.
      H3N2 viruses continue to drift from the vaccine strain and may remain as the
      dominant strains during the 2005-2006 influenza season. Thus, the 2005-2006
      Northern Hemisphere vaccine strain was changed to A/California/7/2004, a virus
      with all 4 amino acid substitutions observed in these Nepalese isolates.

PMID- 16102306
TI  - Cephalosporin-resistant pneumococci and sickle cell disease.
AB  - Sickle cell anemia patients have 600 times the risk for invasive pneumococcal
      disease than their healthy peers. High-level cephalosporin resistance was
      described in the 1990s in healthy children from Tennessee, but its prevalence in
      sickle cell disease patients is unknown. Pneumococcal isolates from sickle cell
      disease patients from Tennessee were subjected to multilocus sequence typing to
      characterize antimicrobial drug-resistant strains. Twenty-one percent of strains
      were resistant to cefotaxime and penicillin. Of the 14 cephalosporin-resistant
      strains, 9 were sequence types previously described as highly cephalosporin
      resistant, while resistance was found for the first time in 3 clones: Maryland6B,
      ST660, and a novel clone, ST1753. High-level cephalosporin resistance exists in
      more settings than initially recognized, and its high prevalence in sickle cell
      disease patients may decrease the efficacy of third-generation cephalosporins in
      invasive pneumococcal disease.

PMID- 16102307
TI  - Pseudomonas aeruginosa, Staphylococcus aureus, and fluoroquinolone use.
AB  - Few long-term multicenter investigations have evaluated the relationships between
      aggregate antimicrobial drug use in hospitals and bacterial resistance. We
      measured fluoroquinolone use from 1999 through 2003 in a network of US hospitals.
      The percentages of fluoroquinolone-resistant Pseudomonas aeruginosa and
      methicillin-resistant Staphylococcus aureus (MRSA) were obtained from yearly
      antibiograms at each hospital. Univariate linear regression showed significant
      associations between a hospital's volume of fluoroquinolone use and percent
      resistance in most individual study years (1999-2001 for P. aeruginosa, 1999-2002
      for S. aureus). When the method of generalized estimating equations was used, a
      population-averaged longitudinal model incorporating total fluoroquinolone use
      and the previous year's resistance (to account for autocorrelation) did not show
      a significant effect of fluoroquinolone use on percent resistance for most drug
      organism combinations, except for the relationship between levofloxacin use and
      percent MRSA. The ecologic relationship between fluoroquinolone use and
      resistance is complex and requires further study.

PMID- 16102308
TI  - Methicillin-resistant Staphylococcus aureus, Hawaii, 2000-2002.
AB  - The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has generated
      considerable concern among medical and public health professionals. We used a
      statewide, population-based antimicrobial resistance surveillance system to
      examine epidemiologic trends for MRSA from outpatients and inpatients in Hawaii.
      Pediatric and adult patient populations were compared to assess characteristics
      of MRSA isolates specific for each group. From 2000 to 2002, 8,206 (26%) of
      31,482 total S. aureus isolates were MRSA. During this period, the proportion of
      MRSA isolates increased in both outpatient and inpatient clinical settings
      (p<0.01). When stratified by age, annual trends showed a significant increase in
      the proportion of MRSA in adult patients (from 24% to 30%, p<0.01) but not in
      pediatric patients (from 25% to 27%, p>0.05). Although MRSA isolates from adults
      demonstrated high resistance to most non-beta-lactams, most MRSA isolates from
      pediatric outpatients remained susceptible to most non-beta-lactams.

PMID- 16102309
TI  - Coxiella burnetii genotyping.
AB  - Coxiella burnetii is a strict intracellular bacterium with potential as a
      bioterrorism agent. To characterize different isolates of C. burnetii at the
      molecular level, we performed multispacer sequence typing (MST). MST is based on
      intergenic region sequencing. These regions are potentially variable since they
      are subject to lower selection pressure than the adjacent genes. We screened 68
      spacers in 14 isolates and selected the 10 that exhibited the most variation.
      These spacers were then tested in 159 additional isolates obtained from different
      geographic areas or different hosts or were implicated in different
      manifestations of human disease caused by C. burnetii. The sequence analysis
      yielded 30 different allelic combinations. Phylogenic analysis showed 3 major
      clusters. MST allows easy comparison and exchange of results obtained in
      different laboratories and could be a useful tool for identifying bacterial
      strains.

PMID- 16102310
TI  - Multidrug-resistant Acinetobacter extremity infections in soldiers.
AB  - War wound infection and osteomyelitis caused by multidrug-resistant (MDR)
      Acinetobacter species have been prevalent during the 2003-2005 military
      operations in Iraq. Twenty-three soldiers wounded in Iraq and subsequently
      admitted to our facility from March 2003 to May 2004 had wound cultures positive
      for Acinetobacter calcoaceticus-baumannii complex. Eighteen had osteomyelitis, 2
      burn infection, and 3 deep wound infection. Primary therapy for these infections
      was directed antimicrobial agents for an average of 6 weeks. All soldiers
      initially improved, regardless of the specific type of therapy. Patients were
      followed up to 23 months after completing therapy, and none had recurrent
      infection with Acinetobacter species. Despite the drug resistance that infecting
      organisms demonstrated in this series, a regimen of carefully selected extended
      antimicrobial-drug therapy appears effective for osteomyelitis caused by MDR
      Acinetobacter spp.

PMID- 16102311
TI  - Human coronavirus NL63, France.
AB  - The human coronavirus NL63 (HCoV-NL63) was first identified in The Netherlands,
      and its circulation in France has not been investigated. We studied HCoV-NL63
      infection in hospitalized children diagnosed with respiratory tract infections.
      From November 2002 to April 2003, we evaluated 300 respiratory specimens for HCoV
      NL63. Of the 300 samples, 28 (9.3%) were positive for HCoV-NL63. The highest
      prevalence was found in February (18%). The main symptoms were fever (61%),
      rhinitis (39%), bronchiolitis (39%), digestive problems (33%), otitis (28%),
      pharyngitis (22%), and conjunctivitis (17%). A fragment of the spike protein gene
      was sequenced to determine the variety of circulating HCoV-NL63. Phylogenetic
      analysis indicated that strains with different genetic markers cocirculate in
      France.

PMID- 16102312
TI  - HIV-1 genetic diversity in antenatal cohort, Canada.
AB  - We studied HIV genetic diversity in a cohort of 127 pregnant, HIV-infected women
      who received prenatal care at Sainte-Justine Hospital in Montreal, Canada,
      between 1999 and 2003. Clade assignments were derived by phylogenetic analysis of
      amplified pol sequences. Genotyping was successful in 103 of 127 women, 59
      (57.3%) of whom were infected with clade B HIV-1, and 44 (42.7%) with nonclade B
      viruses, including subtypes A, C, D, F, G, and H. Four sequences remained
      unassigned. Forty-three of 44 women infected with non-clade B viruses were
      newcomers from sub-Saharan Africa, and subtype identity was consistent with those
      circulating in their countries of origin. These results highlight the
      epidemiologic importance of non-B HIV-1 in antenatal populations in a large North
      American urban center, underscore the influence of population movements on clade
      intermixing, and identify a group of patients who could be targeted for
      surveillance and drug therapy followup.

PMID- 16102313
TI  - Multidrug-resistant Salmonella Typhimurium in four animal facilities.
AB  - In 1999 and 2000, 3 state health departments reported 4 outbreaks of
      gastrointestinal illness due to Salmonella enterica serotype Typhimurium in
      employees, clients, and client animals from 3 companion animal veterinary clinics
      and 1 animal shelter. More than 45 persons and companion animals became ill. Four
      independent investigations resulted in the testing of 19 human samples and >200
      animal samples; 18 persons and 36 animals were culture-positive for S.
      Typhimurium. One outbreak was due to multidrug-resistant S. Typhimurium R-type
      ACKSSuT, while the other 3 were due to multidrug-resistant S. Typhimurium R-type
      ACSSuT DT104. This report documents nosocomial transmission of S. Typhimurium and
      demonstrates that companion animal facilities may serve as foci of transmission
      for salmonellae between animals and humans if adequate precautions are not
      followed.

PMID- 16102314
TI  - Spoligotyping and Mycobacterium tuberculosis.
AB  - We evaluated the clinical usefulness of spoligotyping, a polymerase chain
      reaction-based method for simultaneous detection and typing of Mycobacterium
      tuberculosis strains, with acid-fast bacilli-positive slides from clinical
      specimens or mycobacterial cultures. Overall sensitivity and specificity were 97%
      and 95% for the detection of M. tuberculosis and 98% and 96% when used with
      clinical specimens. Laboratory turnaround time of spoligotyping was less than
      that for culture identification by a median of 20 days. In comparison with IS6110
      based restriction fragment length polymorphism typing, spoligotyping
      overestimated the number of isolates with identical DNA fingerprints by
      approximately 50%, but showed a 100% negative predictive value. Spoligotyping
      resulted in the modification of ongoing antimycobacterial treatment in 40 cases
      and appropriate therapy in the absence of cultures in 11 cases. The rapidity of
      this method in detection and typing could make it useful in the management of
      tuberculosis in a clinical setting.

PMID- 16102315
TI  - Modeling control strategies of respiratory pathogens.
AB  - Effectively controlling infectious diseases requires quantitative comparisons of
      quarantine, infection control precautions, case identification and isolation, and
      immunization interventions. We used contact network epidemiology to predict the
      effect of various control policies for a mildly contagious disease, such as
      severe acute respiratory syndrome, and a moderately contagious disease, such as
      smallpox. The success of an intervention depends on the transmissibility of the
      disease and the contact pattern between persons within a community. The model
      predicts that use of face masks and general vaccination will only moderately
      affect the spread of mildly contagious diseases. In contrast, quarantine and ring
      vaccination can prevent the spread of a wide spectrum of diseases. Contact
      network epidemiology can provide valuable quantitative input to public health
      decisionmaking, even before a pathogen is well characterized.

PMID- 16102316
TI  - Estimating foodborne gastroenteritis, Australia.
AB  - We estimated for Australia the number of cases, hospitalizations, and deaths due
      to foodborne gastroenteritis in a typical year, circa 2000. The total amount of
      infectious gastroenteritis was measured by using a national telephone survey. The
      foodborne proportion was estimated from Australian data on each of 16 pathogens.
      To account for uncertainty, we used simulation techniques to calculate 95%
      credibility intervals (CrI). The estimate of incidence of gastroenteritis in
      Australia is 17.2 million (95% confidence interval 14.5-19.9 million) cases per
      year. We estimate that 32% (95% CrI 24%-40%) are foodborne, which equals 0.3 (95%
      CrI 0.2-0.4) episodes per person, or 5.4 million (95% CrI 4.0-6.9 million) cases
      annually in Australia. Norovirus, enteropathogenic Escherichia coli,
      Campylobacter spp., and Salmonella spp. cause the most illnesses. In addition,
      foodborne gastroenteritis causes approximately 15,000 (95% CrI 11,000-18,000)
      hospitalizations and 80 (95% CrI 40-120) deaths annually. This study highlights
      global public health concerns about foodborne diseases and the need for
      standardized methods, including assessment of uncertainty, for international
      comparison.

PMID- 16102317
TI  - Optimizing treatment of antimicrobial-resistant Neisseria gonorrhoeae.
AB  - The increasing prevalence of ciprofloxacin-resistant Neisseria gonorrhoeae has
      required replacing inexpensive oral ciprofloxacin treatment with more expensive
      injectable ceftriaxone. Further, monitoring antimicrobial resistance requires
      culture testing, but nonculture gonorrhea tests are rapidly replacing culture.
      Since the strategies were similar in effectiveness (> 99%), we evaluated, from
      the healthcare system perspective, cost-minimizing strategies for both diagnosis
      (culture followed by antimicrobial susceptibility tests versus nonculture-based
      tests) and treatment (ciprofloxacin versus ceftriaxone) of gonorrhea in women.
      Our results indicate that switching from ciprofloxacin to ceftriaxone is cost
      minimizing (i.e., optimal) when the prevalence of gonorrhea is > 3% and
      prevalence of ciprofloxacin resistance is > 5%. Similarly, culture-based testing
      and susceptibility surveillance are optimal when the prevalence of gonorrhea is <
      13%; nonculture-based testing is optimal (cost-minimizing) when gonorrhea
      prevalence is > or = 13%.

PMID- 16102318
TI  - Sheep feed and scrapie, France.
AB  - Scrapie is a small ruminant, transmissible spongiform encephalopathy (TSE).
      Although in the past scrapie has not been considered a zoonosis, the emergence of
      bovine spongiform encephalopathy, transmissible to humans and experimentally to
      sheep, indicates that risk exists for small ruminant TSEs in humans. To identify
      the risk factors for introducing scrapie into sheep flocks, a case-control study
      was conducted in France from 1999 to 2000. Ninety-four case and 350 control
      flocks were matched by location and main breed. Three main hypotheses were
      tested: direct contact between flocks, indirect environmental contact, and
      foodborne risk. Statistical analysis was performed by using adjusted generalized
      linear models with the complementary log-log link function, considering flock
      size as an offset. A notable effect of using proprietary concentrates and milk
      replacers was observed. The risk was heterogeneous among feed factories. Contacts
      between flocks were not shown to be a risk factor.

PMID- 16102319
TI  - Cost-benefit of stockpiling drugs for influenza pandemic.
AB  - We analyzed strategies for the use of stockpiled antiviral drugs in the context
      of a future influenza pandemic and estimated cost-benefit ratios. Current
      stockpiling of oseltamivir appears to be cost-saving to the economy under several
      treatment strategies, including therapeutic treatment of patients and
      postexposure prophylactic treatment of patients' close contacts.

PMID- 16102320
TI  - Staphylococcus lugdunensis pacemaker-related infection.
AB  - We report the first known case of a device-related bloodstream infection
      involving Staphylococcus lugdunensis small-colony variants. Recurrent pacemaker
      related bloodstream infection within a period of 10 months illustrates the poor
      clinical and microbiologic response even to prolonged antimicrobial drug therapy
      in a patient infected with this staphylococcal subpopulation.

PMID- 16102321
TI  - Bartonella quintana in domestic cat.
AB  - We recovered Bartonella quintana DNA from dental pulp of a domestic cat. This
      study, the first to detect B. quintana in a nonhuman mammal, changes our
      understanding of the epidemiology of this infection and proposes that cats may be
      an emerging source of human infection.

PMID- 16102322
TI  - Malaria and irrigated crops, Accra, Ghana.
AB  - We investigated the prevalence of malaria and associated risk factors in children
      living in urban Ghana. Malaria prevalence was associated with low hemoglobin
      concentration, low socioeconomic status, and higher age. Our findings indicate
      that African urban poor are seriously affected by malaria and that irrigated
      agriculture may increase this risk.

PMID- 16102323
TI  - West Nile virus detection in urine.
AB  - We report West Nile virus (WNV) RNA in urine collected from a patient with
      encephalitis 8 days after symptom onset. Viral RNA was detected by reverse
      transcriptase-polymerase chain reaction (RT-PCR). Sequence and phylogenetic
      analysis confirmed the PCR product to have > or = 99% similarity to the WNV
      strain NY 2000-crow3356.

PMID- 16102324
TI  - Posttraumatic stress after SARS.
AB  - Posttraumatic stress disorder (PTSD) can arise in patients with medical illness.
      We used 2 Chinese self-report measures to examine features of PTSD, anxiety, and
      depression in 131 survivors of severe acute respiratory syndrome at 1 month and 3
      months after discharge from the hospital. Risk factors associated with
      psychological distress were identified.

PMID- 16102325
TI  - Evaluating antibiograms to monitor drug resistance.
AB  - We used hospital antibiograms to assess predominant pathogens and their patterns
      of in vitro antimicrobial resistance in central Illinois, USA. We found a lack of
      information about national guidelines for in vitro antimicrobial susceptibility
      testing and differences in interpretation among laboratories in the region.

PMID- 16102326
TI  - Influenza A H5N1 detection.
AB  - We developed a sensitive and rapid real-time reverse transcription-polymerase
      chain reaction (RT-PCR) assay to detect influenza A H5N1 virus in clinical
      samples. This assay was evaluated with samples from H5N1-infected patients and
      demonstrated greater sensitivity and faster turnaround time than nested RT-PCR.

PMID- 16102327
TI  - Drug-resistant diarrheogenic Escherichia coli, Mexico.
AB  - Diarrheogenic Escherichia coli isolates from 45 (73%) of 62 hospitalized patients
      were resistant to common antimicrobial drugs. Sixty-two percent were multidrug
      resistant, and >70% were resistant to trimethoprim-sulfamethoxazole and
      ampicillin. Ciprofloxacin and cefotaxime were uniformly active. Effective and
      safe oral agents are needed to treat children with bacterial diarrhea.

PMID- 16102372
TI  - Historical trends in the production and consumption of illicit drugs in Mexico:
      implications for the prevention of blood borne infections.
AB  - Mexico has cultivated opium poppy since before the 1900's and has been an
      important transit route for South American cocaine for decades. However, only
      recently has drug use, particularly injection drug use, been documented as an
      important problem. Heroin is the most common drug used by Mexican injection drug
      users (IDUs). Increased cultivation of opium poppy in some Mexican states, lower
      prices for black tar heroin and increased security at U.S.-Mexican border
      crossings may be contributing factors to heroin use, especially in border cities.
      Risky practices among IDUs, including needle sharing and shooting gallery
      attendance are common, whereas perceived risk for acquiring blood borne
      infections is low. Although reported AIDS cases attributed to IDU in Mexico have
      been low, data from sentinel populations, such as pregnant women in the Mexican
      U.S. border city of Tijuana, suggest an increase in HIV prevalence associated
      with drug use. Given widespread risk behaviors and rising numbers of blood borne
      infections among IDUs in Mexican-U.S. border cities, there is an urgent need for
      increased disease surveillance and culturally appropriate interventions to
      prevent potential epidemics of blood borne infections. We review available
      literature on the history of opium production in Mexico, recent trends in drug
      use and its implications, and the Mexican response, with special emphasis on the
      border cities of Ciudad Juarez and Tijuana.

PMID- 16102373
TI  - Reductions in criminal convictions after addiction treatment: 5-year follow-up.
AB  - Changes in criminal convictions were investigated among 1075 clients admitted to
      54 drug misuse treatment services across England as part of the National
      Treatment Outcome Research Study (NTORS). Convictions data during the year prior
      to treatment, and at 1 year, 2 years, and 5 years after treatment intake were
      collected from the Home Office Offenders' Index, a national database of all
      convictions in adult and youth courts. Clinical data were collected by face-to
      face interviews at intake to treatment, and at follow-up 1 year, 2 years, and 4-5
      years after admission to treatment. During the year prior to treatment, 34% of
      the sample had been convicted of at least one offence. Conviction rates at all
      follow-up points were significantly lower than at intake. During the year prior
      to the 5-year follow-up, 18% of the sample had been convicted of at least one
      offence. Statistically significant reductions in the mean number of convicted
      offences were also found between treatment intake and 5-year follow-up.
      Reductions in convictions were found for acquisitive, drug selling, and violent
      crimes. Reductions in crime were associated with reductions in regular heroin
      use, age, and with stable housing. The results replicate previously reported
      findings of crime reductions among the NTORS cohort as indicated by self-reported
      measures of offending behaviour. The observed reductions in crime among drug
      misusers after treatment represent substantial changes in behaviour and have
      considerable personal, social and clinical significance. Reduced criminality also
      provides substantial economic benefits to society.

PMID- 16102374
TI  - Examining the influence of drop-outs in a follow-up of maintained opiate users.
AB  - INTRODUCTION: In most longitudinal studies of problem opiate users, drop-outs are
      frequent, but not taken into account. However, missing data can induce important
      bias in parameters estimates. OBJECTIVE: The aim of this study was to examine the
      influence of drop-outs in the statistical analysis of a follow-up of opiate users
      in maintenance treatment. METHODS: Participants were 519 patients who had sought
      maintenance treatment between 1994 and 2001. Drug use was studied using the drug
      composite score of the Addiction Severity Index. A classical data analysis
      (linear mixed effects model for repeated measurements) was compared with a
      selection model, which consists, in this case, of a joint modelling of the score
      and of the drop-out probability in order to reduce bias induced by drop-outs.
      RESULTS: At 18 months, 38% of the patients were available for evaluation. Drop
      outs were associated with low drug use and were informative. Each model showed
      that the score decreased over time and that it was associated with psychiatric
      problems. Unlike the classical method, the joint model showed no significant
      association between the score and age or treatment setting. CONCLUSIONS: These
      results show the importance of accounting for informative drop-outs in data
      analysis before drawing conclusions from such studies.

PMID- 16102375
TI  - The increase in the association of education and cocaine use over the 1980s and
      1990s: evidence for a 'historical period' effect.
AB  - During the 1980s the social distribution of adult cocaine use in the US changed,
      according to qualitative analyses, and its use became more prevalent in the lower
      as compared to the upper social strata. In this paper, we use national data to
      investigate the association of education and adult cocaine use to test whether
      this trend represents either a 'historical period' process that occurred
      concurrently across adults of all age groups or a cohort process that started
      with younger cohorts and only extended to older age groups as these younger
      cohorts aged. We also estimate the extent to which the emergence of crack cocaine
      use accounts for trends in the socioeconomic distribution of cocaine use over
      historical time. To address these questions we analyze data from each survey of
      the National Household Survey on Drug Abuse from 1979 to 1998 inclusive. The
      results point to a "historical period" process that is explained in large part-
      but not entirely--by the emergence of crack cocaine. Important differences are
      apparent across racial and ethnic groups, as well as age groups. Cocaine use
      joins a growing list of potentially addictive drugs that have become more
      prevalent in the lower as compared to the upper social strata over historical
      time.

PMID- 16102376
TI  - The video assessment of simulated encounters (VASE): Development and validation
      of a group-administered method for evaluating clinician skills in motivational
      interviewing.
AB  - The authors developed and evaluated a group-administered method for measuring
      motivational interviewing (MI) skills. The video assessment of simulated
      encounters (VASE) consists of three videotaped vignettes of actors playing
      substance abusers. Each vignette is followed by eight questions asking examinees
      to generate written responses consistent with MI principles. Twenty-two
      clinicians completed the VASE questionnaire and two other measures of MI skill: a
      paper-and-pencil measure that elicited responses to written scenarios and an
      audiotaped interaction with a standardized patient (SP), subsequently scored for
      MI skill by independent tape raters. Psychometric analyses of this original VASE
      scale evaluated: (1) scoring reliability of the 24 VASE items; (2) internal
      reliability of the VASE full-scale score, seven subscale scores and the three
      vignettes; and (3) concurrent validity with aforementioned indices of MI skill.
      Analyses informed the removal of two subscales, redesign of a third and revisions
      to a fourth. The resulting 18-item VASE-R scale retains its three-vignette
      format, and assesses overall MI skill as well as the following five MI
      "microskills": reflective listening, responding to resistance, summarizing,
      eliciting change talk and developing discrepancy. The VASE-R requires further
      analysis to evaluate these revisions, but shows promise as a cost-effective
      alternative for use in MI skill assessment in a variety of training and research
      contexts.

PMID- 16102377
TI  - Brain catalase mediates potentiation of social recognition memory produced by
      ethanol in mice.
AB  - The involvement of catalase in ethanol-induced locomotion has been clearly
      proven. However, studies addressing the role of this enzyme in the effects that
      ethanol exerts on memory are lacking. In the present study, the social
      recognition test (SRT) was used to evaluate ethanol effects on memory. In this
      test, the reduction in investigation time of a juvenile conspecific, when this
      social stimulus is presented for the second time, is considered a reliable index
      of memory. Exploration ratios (ER) were calculated to evaluate the recognition
      capacity of mice. Ethanol (0.0, 0.5, 1.0 or 1.5g/kg, i.p.) was administered
      immediately after the first juvenile presentation, and 2h later the juvenile was
      re-exposed to the adult. Additionally, adult mice received aminotriazole (AT) or
      sodium azide (two catalase inhibitors) 5h or 30 min before juvenile presentation,
      respectively. Ethanol (1.0 and 1.5g/kg) was able to reduce ER, indicating an
      improving effect on memory. This improvement was prevented by either AT or sodium
      azide pre-treatment. However, neither AT nor sodium azide attenuated the memory
      enhancing capacity of NMDA or nicotine, suggesting a specific interaction between
      catalase inhibitors and ethanol in their effects on memory. The present results
      suggest that brain catalase activity could mediate the memory-enhancing capacity
      of ethanol and add further support to the idea that this enzyme mediates some of
      the psychopharmacological effects produced by ethanol.

PMID- 16102378
TI  - Emergency department-based intervention with adolescent substance users: 12-month
      outcomes.
AB  - We evaluated the 12-month outcomes of a brief intervention, enhanced by a
      consistent support person, which aimed to facilitate referral attendance for
      substance use treatment following a hospital alcohol or other drug (AOD)
      presentation. Outcomes were assessed as: attendance for substance use treatment;
      the number of hospital AOD ED presentations; change in AOD consumption and
      psychological wellbeing (GHQ-12). We recruited 127 adolescents, with 60
      randomised to the intervention and 67 receiving usual care. At 12 months, 87
      (69%) were re-interviewed. Significantly more of the intervention than the usual
      care group (12 versus 4) had attended a treatment agency. Excluding the index
      presentations, there were 66 AOD hospital presentations post intervention, with
      the proportion of AOD events falling for the intervention group, whilst no change
      occurred for the usual care group. Irrespective of randomisation, those who
      attended for substance use treatment had a greater decline in total self-reported
      drug use than the remainder. Both intervention and usual care groups had improved
      GHQ-12 scores by 12 months, with reduction in GHQ scores correlated with reduced
      drug use. In conclusion, while brief intervention in ED only has limited success
      in facilitating adolescents to attend for subsequent AOD treatment, it can
      significantly reduce the number of AOD related ED presentations.

PMID- 16102379
TI  - Effects of item sequence on the performance of the AUDIT in general practices.
AB  - BACKGROUND: One important task in identifying subjects with alcohol use disorders
      (AUDs) in the general medical practice setting is the development of effective
      screening instruments. Sensitivity of screening questionnaires might differ
      according to the introductory items. This study compares two versions of the
      alcohol use disorders identification test (AUDIT) with varied item sequence
      randomly applied to patients derived from a sample of general practitioners (GP)
      patients. METHODS: Participants were recruited from general practices in two
      northern German cities; they received two different versions of the AUDIT, one
      group receiving the original version starting with three items addressing
      frequency and quantity of alcohol use (AUDIT1), and a second group receiving a
      version in which these items were put at the end of the questionnaire (AUDIT2).
      In total, 10.803 screenings were conducted (refusal rate: 5%). Alcohol use
      disorders were diagnosed using the Munich-Composite International Diagnostic
      Interview (M-CIDI). RESULTS: Logistic regression analysis revealed that AUDIT1
      subjects had higher scores in the consumption items of the AUDIT, whereas AUDIT2
      subjects scored higher on items focussing on symptoms of alcohol dependence or
      abuse. CONCLUSION: The sequence upon which items of the AUDIT are presented
      influences the report of drinking patterns and symptoms of alcohol use disorders
      in GP patients.

PMID- 16102380
TI  - DRD2 genotypes and substance use in adolescent children of alcoholics.
AB  - Research has identified children of alcoholics (COAs) as a population at
      increased risk for developing substance use problems. Genetic studies support the
      Al allele of the D2 dopamine receptor gene (DRD2) as a risk marker for alcoholism
      and substance use disorders. In this study, substance use was assessed in 48
      adolescent boys of alcoholics with the DRDR A1(+) allele (A1A1/A1A2 genotypes) or
      the A1(-) allele (A2A2 genotype). The results revealed that boys with the A1(+)
      allele tried (p=0.0001) and got intoxicated on alcohol more often (p=0.009) than
      boys with the A1(-) allele. Boys with the A1(+) allele tried more (p=0.004) and
      used more substances overall (p=0.008) than boys with the A1(-) allele. Boys with
      the A1(+) allele developed a tobacco habit more often (p=0.03) and experienced
      marijuana high at an earlier age (p=0.001) than boys with the A1(-) allele. The
      best predictors of substance use severity in boys with the A1(+) allele were
      Psychoticism (p=0.01) and Negative Affect (p=0.04). The results provide support
      for the DRD2 A1 allele as a marker identifying a subgroup of COAs at high risk
      for developing substance use problems.

PMID- 16102381
TI  - Association of sex, hygiene and drug equipment sharing with hepatitis C virus
      infection among non-injecting drug users in New York City.
AB  - BACKGROUND: Hepatitis C virus (HCV) rates are higher in non-injecting drug users
      (NIDUs) than general population estimates. Whether this elevated HCV rate is due
      to drug use or other putative risk behaviors remains unclear. METHODS: Recent non
      injection drug users of heroin, crack and/or cocaine were street-recruited from
      2000 to 2003 and underwent an interview and venipuncture for HCV antibody assays.
      Multiple logistic regression analyses were used to assess correlates for HCV
      infection. RESULTS: Of 740 enrollees, 3.9% were HCV positive. The median age
      (intraquartile range) was 30 (35-24) years, 70% were male and 90% were Black or
      Hispanic. After adjustment, HCV seropositives were significantly more likely than
      seronegatives to be older than 30 [adjusted odds ratio (AOR)=5.71], tattooed by a
      friend/relative/acquaintance [AOR=3.61] and know someone with HCV [AOR=4.29], but
      were less likely to have shared nail or hair clippers, razors or a toothbrush
      [AOR=0.32]. CONCLUSIONS: Non-commercial tattooing may be a mode of HCV
      transmission among NIDUs and education on the potential risk in using non-sterile
      tattooing equipment should be targeted toward this population. While no evidence
      was found for HCV transmission through NIDU equipment sharing or sexual risk
      behavior, further research is still warranted.

PMID- 16102383
TI  - Cross talk between nucleus and organelles. Proceedings of a meeting. September 15
      18, 2004. Naples, Italy.

PMID- 16102382
TI  - Mortality among subjects previously apprehended for driving under the influence
      of traffic-hazardous medicinal drugs.
AB  - BACKGROUND: Most studies in the field of impaired driving have focused on the
      hazards represented by impaired drivers to the rest of society; there has been
      little follow-up of the drivers themselves. The aim of this study was to
      establish mortality rates among subjects previously apprehended for driving under
      the influence of traffic-hazardous medicinal drugs, alone or in combination with
      alcohol. METHODS: A prospective cohort study of all drivers aged 20-49 years,
      apprehended in Norway in 1992-1996 and testing positive for traffic-hazardous
      medicinal drugs in blood, outcome variable: death. STUDY POPULATION: 805 drivers
      (598 males, 207 females). Mean follow-up period: 6.8 years. Information on deaths
      was collected from Statistics Norway. RESULTS: During the follow-up period, 139
      of the previously apprehended drivers died (110 males, 29 females). The
      calculated standardised mortality ratio (SMR) was 15.8 (95% CI: 13.0-19.0) for
      male and 20.0 (95% CI: 13.4-28.7) for female drivers. CONCLUSIONS: Apprehension
      on suspicion of driving under the influence of drugs, combined with detection of
      traffic-hazardous medicinal drugs in the blood, seems to indicate an elevated
      risk of premature death in the age group 20-49 years. Secondary prevention of
      continued drug use could save lives in this drug user group.

PMID- 16102385
TI  - AAO maintains your continuing education credits from AAO-sponsored events,
      publications.

PMID- 16102386
TI  - Unusual transmigration of an impacted canine.

PMID- 16102388
TI  - Formaldehyde from POM brackets.

PMID- 16102390
TI  - Hemisection treatment of second deciduous molars.

PMID- 16102392
TI  - Evidence-based versus experience-based views on occlusion and TMD.

PMID- 16102394
TI  - The money trail.

PMID- 16102395
TI  - ADA initiates development of orthodontic informatics standards.
AB  - Standards are the key to interoperability across systems. The American Dental
      Association (ADA) has been accredited by the American National Standards
      Institute (ANSI) as a standards-developing organization. The ADA sponsors
      standards programs for all areas of dentistry, including dental materials and
      products and dental informatics. ANSI/ADA Specification No. 1000, Standard
      Clinical Data Architecture for the Structure and Content of an Electronic Health
      Record, is the first ANSI standard that defines the fundamental data structures
      used to make patient health records. The standard promotes the sharing of like
      data between dentists, physicians, and hospitals.

PMID- 16102396
TI  - Comparing digital and conventional cephalometric radiographs.
AB  - With the introduction of digital cephalometry in orthodontics, many clinicians
      have cephalometric radiographs for a patient taken on 2 different cephalostats.
      Comparing these images is difficult because of differences in magnification
      between the 2 units. This article describes how to determine the magnification of
      a cephalometric radiograph and how to change the dimensions of a digital image to
      match a conventional image.

PMID- 16102397
TI  - Comparing digital serial cephalogram images for growth or treatment changes.
AB  - Superimposing serial radiographs is an easy method for assessing growth changes
      or treatment progress. Conventional films could be superimposed manually over a
      light box. The layering and variable-opacity features of digital imaging software
      can be used to superimpose digital images on your computer screen. Digital
      imaging software can be used to compare digital radiographs to identify growth
      patterns or treatment progress.

PMID- 16102398
TI  - Perceptions and attitudes of Canadian orthodontists regarding digital and
      electronic technology.
AB  - INTRODUCTION: To plan for future acceptance and implementation of computer
      related technology, it is necessary to understand orthodontists' current
      perceptions and attitudes toward emerging technologies. METHODS: An anonymous,
      self-administered, mail-out survey of Canadian orthodontists was conducted. The
      response rate was 45.6% (304/667). RESULTS: Most orthodontists indicated that
      computer technology could improve current practice efficiency and quality of
      patient care. Only 15% reported that digital models are quite or very useful;
      73.6%, 69.1%, 55%, and 37.4% agreed or strongly agreed with using digital and
      electronic technology to consult with other dental specialists, other
      orthodontists, general dentists, and the public, respectively. Cost of the
      technology was reported as a significant or insurmountable obstacle by 54% of the
      respondents. Interprovincial legislation, unclear consultation remuneration
      guidelines, and lack of comfort with the technology were not perceived as
      significant obstacles. Only 36% reported security or privacy issues as a
      significant or insurmountable obstacle. CONCLUSIONS: Canadian orthodontists seem
      to view digital and electronic technology as useful and capable of improving
      their offices' efficiency and production. Although they are sensitive to some
      potential obstacles, they are willing to overcome these and incorporate the
      technology into their practices.

PMID- 16102399
TI  - Radiation protection guidelines for the practicing orthodontist.
AB  - This article summarizes the most recent (December 2003) dental x-ray guidelines
      from the National Council on Radiation Protection and Measurements report #145.
      The guidelines are intended for all dental health-care providers. They address
      radiation dose limits for occupational and nonoccupational exposure and radiation
      protection for operators, patients, and the public. Equipment design can play an
      important role in radiation protection, and recommendations from the guidelines
      are discussed.

PMID- 16102401
TI  - Peri-implant bone response to orthodontic loading: Part 1. A histomorphometric
      study of the effects of implant surface design.
AB  - INTRODUCTION: Bone response to orthodontic loading was compared
      histomorphometrically around 2 different types of osseointegrated implants
      (porous surfaced and machined threaded) to determine their suitability for
      orthodontic anchorage. METHODS: Five beagles each received 3 implants of each
      design in contralateral mandibular locations. After a 6-week initial healing
      period, abutments were placed, and, 1 week later, the 2 mesial implants on each
      side were orthodontically loaded for 22 weeks. All implants remained
      osseointegrated throughout orthodontic loading except for 1 threaded implant that
      loosened. Light miscroscopy and back-scattered scanning electron microscopy were
      used to compare responses around the 2 implant designs. RESULTS: Porous-surfaced
      implants had higher marginal bone levels (P +/- .025) and less relative implant
      displacement than threaded implants. CONCLUSIONS: Differences in implant surface
      design can lead to differences in peri-implant bone height and bone-to-implant
      contact. Porous-surfaced implants might be successful as orthodontic anchorage
      units.

PMID- 16102402
TI  - Peri-implant bone response to orthodontic loading: Part 2. Implant surface
      geometry and its effect on regional bone remodeling.
AB  - INTRODUCTION: Bone response to orthodontic loading was compared around 2
      different types of osseointegrated implants (porous surfaced and machined
      threaded) to determine the effect of implant surface geometry on regional bone
      remodeling. METHODS: Five beagles each received 3 implants of each design in
      contralateral mandibular extraction sites. After a 6-week initial healing period,
      abutments were placed, and, 1 week later, the 2 mesial implants on each side were
      orthodontically loaded for 22 weeks. All implants remained osseointegrated
      throughout orthodontic loading except for 1 threaded implant that loosened. Back
      scattered scanning electron microscopy and fluorochrome bone labeling techniques
      were used to compare responses around the 2 types of implants. RESULTS: The
      loaded, porous-surfaced implants had significantly higher marginal bone levels
      and greater bone-to-implant contact than did the machined-threaded implants.
      CONCLUSIONS: Significant differences in peri-implant bone remodeling and bone
      formation in response to controlled orthodontic loading were observed for the 2
      implant designs. Short, porous-surfaced implants might be more effective for
      orthodontic applications than machine-threaded implants.

PMID- 16102403
TI  - Histomorphometric and mechanical analyses of the drill-free screw as orthodontic
      anchorage.
AB  - INTRODUCTION: Drill-free screws were developed to provide convenient orthodontic
      anchorage. The purpose of this study was to evaluate the effects of the drilling
      procedure on the stability of the screws under early orthodontic loading.
      METHODS: Thirty-two screws were inserted into the jaws of 2 beagles. The screws
      were divided into 2 groups of 16: the drilling group and the drill-free group.
      Screws in the drilling group were inserted into the site that had been drilled
      with a pilot drilling bur, and those in the drill-free group were inserted
      without drilling. A force of 200 to 300 g was applied using nickel-titanium coil
      springs 1 week after insertion. Twelve weeks after insertion, mobility was tested
      with Periotest (Siemens AG, Bensheim, Germany), and the screws with the
      surrounding bone were prepared for histomorphometric evaluation. RESULTS: Screws
      in the drill-free group showed less mobility and more bone-to-metal contact; they
      had more bone area compared with the drilling group, although bone
      osseointegration was generally found in both groups. CONCLUSIONS: With careful
      technique, drill-free screws can provide stable orthodontic anchorage.

PMID- 16102404
TI  - Centrographic analysis of 1-phase versus 2-phase treatment for Class II
      malocclusion.
AB  - INTRODUCTION: Cephalometric analyses have been used by orthodontists to track
      growth and monitor treatment effects. Most of these analyses have normative
      values to which patients are compared, but some "normal" patients vary quite a
      bit from the normative values. The centrographic analysis is a visual analysis
      with no angles to measure or normative values to compare. After a reference plane
      is developed, the relative position of variable landmarks can be seen. METHODS:
      We used the centroid centrographic analysis to study the effects of 1-phase and 2
      phase orthodontic treatment. Phase 1 treatment consisted of bionator (n = 66),
      headgear/biteplane (n = 69), or observation (n = 65) until a Class I molar
      relationship was achieved or 2 years had elapsed. After 1 year, all subjects
      underwent full orthodontic treatment with fixed appliances. RESULTS:
      Centrographic analysis showed that early treatment has effects on the mandible.
      However, the differences were not apparent by the end of fixed appliance
      treatment. CONCLUSIONS: The skeletal effects of phase 1 treatment disappear by
      the end of fixed appliance treatment.

PMID- 16102405
TI  - Professional assessment of facial profile attractiveness.
AB  - INTRODUCTION: The aim of this study was to compare the assessments of Chinese
      facial profile attractiveness by orthodontists and oral surgeons. METHODS: The
      sample comprised 31 dental professionals (20 orthodontists, 11 oral surgeons) in
      an Asian community. Facial profile photographs and lateral cephalometric
      radiographs of 2 Chinese adults (1 man, 1 woman) with normal profiles, Class I
      incisor relationships, and Class I skeletal patterns were digitized. The digital
      images were modified by altering cephalometric skeletal and dental hard tissue
      Chinese normative values in increments of 2 standard deviations in the
      anteroposterior plane to obtain 7 facial profiles for each sex. The images were
      bimaxillary protrusion, protrusive mandible, retrusive mandible, normal profile
      (Class I incisor with Class I skeletal pattern), retrusive maxilla, protrusive
      maxilla, and bimaxillary retrusion. The Mann-Whitney U test was used to determine
      professional differences in assessment. Multiple regression analysis was
      performed with age, professional status, sex, and number of years in practice as
      independent variables. RESULTS AND CONCLUSIONS: A strong correlation was found in
      the profile assessment between orthodontists and oral surgeons. Normal and
      bimaxillary retrusive Chinese male and female profiles were judged to be highly
      attractive by orthodontists and oral surgeons. Chinese male and female profiles
      with protrusive mandibles were judged the least attractive. There was a
      difference in professional opinion about the most attractive male profile (P <
      .05), with orthodontists preferring a flatter profile and oral surgeons
      preferring a fuller normal Chinese profile. Sex of dental professionals and
      number of years in clinical practice were found to affect profile rankings.

PMID- 16102406
TI  - Anteroposterior lip positions of the most-favored Japanese facial profiles.
AB  - INTRODUCTION: Soft tissue analysis is a basic tool in planning orthodontic
      treatment. However, the components of a well-balanced Japanese facial profile
      have not yet been established. The purpose of this study was to assess the most
      favored or most well-balanced profile from a series of facial silhouettes with
      varying anteroposterior lip positions by a group of Japanese orthodontists and a
      group of young adult Japanese dental students. METHODS: Average female and male
      profiles were constructed from the profiles of 30 Japanese men and women with
      normal occlusions. The lips in each average profile were protruded or retruded in
      1-mm increments, and the 13 images were arranged with the average profile in the
      center. Forty two orthodontists and 42 dental students were asked to select the 3
      most-favored, well-balanced profiles for each sex and rank them in order of
      preference. RESULTS: Both the orthodontists and the students preferred a profile
      with slightly retruded lips. The dental students favored a more retruded lip
      position for women. The least-favored profile was the most protrusive.
      CONCLUSIONS: These findings suggest that Japanese orthodontists and young adults
      prefer a retruded profile, even though Japanese profiles have historically been
      characterized by more convex facial features.

PMID- 16102407
TI  - True incisor intrusion attained during orthodontic treatment: a systematic review
      and meta-analysis.
AB  - INTRODUCTION: The purpose of this meta-analysis was to quantify the amount of
      true incisor intrusion attained during orthodontic treatment. METHODS: Electronic
      databases (PubMed, Medline, Medline In-Process & Other Non-Indexed Citations, all
      EBM reviews [Cochrane Database of Systematic Reviews, ASP Journal Club, DARE, and
      CCTR], Embase, Web of Science, and Lilacs) were searched with the help of a
      senior health sciences librarian. The goal was to identify clinical trials that
      assessed true incisor intrusion through cephalometric analysis and factored out
      craniofacial growth when required. From the selected abstracts, original articles
      were retrieved, and their references were hand searched for missing articles.
      RESULTS: Twenty-eight articles met the initial inclusion criteria, but 24 were
      rejected because they did not quantify true incisor intrusion or factor out
      normal growth impact when required. The remaining 4 articles showed that true
      incisor intrusion is attainable (0.26 to 1.88 mm for the maxillary incisors and 
      0.19 to 2.84 mm for the mandibular incisors) but with large variability depending
      on the appliance used. A meta-analysis with results from the 2 articles that used
      the segmental technique was completed. The combined mean estimates of intrusion
      and 95% CI were 1.46 mm (1.05-1.86 mm) for the maxillary incisors and 1.90 mm
      (1.22-2.57 mm) for the mandibular incisors. CONCLUSIONS: True incisor intrusion
      is achievable in both arches, but the clinical significance of the magnitude of
      true intrusion as the sole treatment option is questionable for patients with
      severe deepbite. In nongrowing patients, the segmented arch technique can produce
      1.5 mm of incisor intrusion in the maxillary arch and 1.9 mm in the mandibular
      arch.

PMID- 16102408
TI  - Intra-arch occlusal indicators of crowding in the permanent dentition.
AB  - INTRODUCTION: The objective of this study was to identify the intra-arch occlusal
      characteristics that best discriminated 3 groups with different grades of dental
      arch discrepancies. This cross-sectional analysis was conducted in Lima, Peru, in
      2003. METHODS: Intra-arch measurements were made on 150 sets of dental casts of
      high school students (aged 12-16; 75 boys, 75 girls). Stepwise multiple
      discriminant analysis (SMDA) was used to obtain a better understanding of the
      morphological relationships between tooth and dental-arch variables and their
      relationship with crowding. RESULTS: Mesiodistal tooth sizes and crown
      proportions of some teeth differed among significantly crowded, mild-to
      moderately crowded, and spaced dental arches. Buccolingual tooth sizes were
      similar in the 3 groups. Of the arch dimensions evaluated, only intermolar arch
      width and arch length differed between the groups. An SMDA was developed to
      classify dental-arch discrepancies in the permanent dentition based on several
      intra-arch occlusal characteristics. The variable with the highest discriminatory
      capability between groups was arch length. When arch length was taken out of the
      SMDA, the explanatory capability from the variability on the dental arch
      discrepancies diminished from 51% to 14%. When the remaining arch dimension
      variable (intermolar width) was taken out, the explanatory capability diminished
      more (from 14% to 8%). CONCLUSIONS: Although other tooth-size and arch dimensions
      are indicators of crowding, arch length is the most important factor.

PMID- 16102409
TI  - Intermaxillary tooth size discrepancy and mesiodistal crown dimensions for a
      Turkish population.
AB  - INTRODUCTION: The aims of this study were to determine the size of individual
      permanent teeth, tooth-size ratios for the maxillary and mandibular dentitions,
      and sex differences for those variables in a Turkish population, and to compare
      the figures obtained with those of the Bolton analysis. METHODS: The data were
      derived from dental casts of 150 Turkish subjects (72 men, mean age 22.09 +/-
      3.11 years; 78 women, mean age, 21.11 +/- 2.08 years) with normal occlusions. The
      mean, standard deviation, and minimum and maximum values were calculated for
      individual tooth size, and overall and anterior ratios, separately for men and
      women. To determine whether there are sex differences in intermaxillary tooth
      size discrepancies, an independent samples t test was performed. RESULTS: The
      mesiodistal dimensions of the maxillary teeth showed greater variability than the
      mandibular teeth, with the first molar dimensions having the greatest
      variability. The overall and anterior ratios were found to be 89.88 +/- 2.29 and
      78.26 +/- 2.61, respectively. A statistically significant sex difference was
      found only in overall ratio (P < .001). According to Bolton's mean values, a
      discrepancy in the overall ratio was found in 18% of Turkish normal occlusion
      subjects, and anterior ratios outside 2 standard deviations from the Bolton mean
      were found in 21.3% of our sample. CONCLUSIONS: These findings indicate that
      population-specific standards are necessary for clinical assessments. Bolton's
      original data do not represent Turkish people, and therefore it is appropriate to
      use Turkish norms in daily orthodontic practice for Turkish patients.

PMID- 16102410
TI  - Category 6: Class II Division 1 malocclusion treated with extraction of permanent
      teeth.

PMID- 16102411
TI  - Labially displaced ectopically erupting maxillary permanent canine: interceptive
      treatment and long-term results.
AB  - This case report demonstrates how extracting a maxillary deciduous canine affects
      the eruption path of a labially displaced ectopically erupting permanent canine.
      A long-term follow-up is presented, and the biologic mechanisms are discussed.

PMID- 16102412
TI  - Orthodontics in 3 millennia. Chapter 4: the professionalization of orthodontics
      (concluded).
AB  - Angle's legacy was assured when his disciples, both in the United States and
      abroad, boarded the joiners' bandwagon. The first 2 cornerstones of the
      professional pyramid were laid (education and organization), and the specialty
      began to pour the third cornerstone: orthodontic literature. Anthropologists,
      anatomists, histologists, and health professionals laid the foundation for the
      study of craniofacial growth.

PMID- 16102413
TI  - Litigation, legislation, and ethics. The modern version of a professional
      chastity belt.

PMID- 16102414
TI  - Identification and recombinant expression of a novel chymotrypsin from Spodoptera
      exigua.
AB  - A novel chymotrypsin which is expressed in the midgut of the lepidopteran insect
      Spodoptera exigua is described. This enzyme, referred to as SeCT34, represents a
      novel class of chymotrypsins. Its amino-acid sequence shares common features of
      gut chymotrpysins, but can be clearly distinguished from other serine proteinases
      that are expressed in the insect gut. Most notable, SeCT34 contains a
      chymotrypsin activation site and the highly conserved motive DSGGP in the
      catalytic domain around the active-site serine is changed to DSGSA. Recombinant
      expression of SeCT34 was achieved in Sf21 insect cells using a special
      baculovirus vector, which has been engineered for optimized protein production.
      This is the first example of recombinant expression of an active serine
      proteinase which functions in the lepidopteran digestive tract. Purified
      recombinant SeCT34 enzyme was characterized by its ability to hydrolyze various
      synthetic substrates and its susceptibility to proteinase inhibitors. It appeared
      to be highly selective for substrates carrying a phenylalanine residue at the
      cleavage site. SeCT34 showed a pH-dependence and sensitivity to inhibitors, which
      is characteristic for semi-purified lepidopteran gut proteinases. Expression
      analysis revealed that SeCT34 was only expressed in the midgut of larvae at the
      end of their last instar, just before the onset of pupation. This suggests a
      possible role of this protein in the proteolytic remodelling that occurs in the
      gut during the larval to pupal molt.

PMID- 16102415
TI  - Acquisition, transformation and maintenance of plant pyrrolizidine alkaloids by
      the polyphagous arctiid Grammia geneura.
AB  - The polyphagous arctiid Grammia geneura appears well adapted to utilize for its
      protection plant pyrrolizidine alkaloids of almost all known structural types.
      Plant-acquired alkaloids that are maintained through all life-stages include
      various classes of macrocyclic diesters (typically occurring in the Asteraceae
      tribe Senecioneae and Fabaceae), macrocyclic triesters (Apocynaceae) and open
      chain esters of the lycopsamine type (Asteraceae tribe Eupatorieae, Boraginaceae
      and Apocynaceae). As in other arctiids, all sequestered and processed
      pyrrolizidine alkaloids are maintained as non-toxic N-oxides. The only type of
      pyrrolizidine alkaloids that is neither sequestered nor metabolized are the pro
      toxic otonecine-derivatives, e.g. the senecionine analog senkirkine that cannot
      be detoxified by N-oxidation. In its sequestration behavior, G. geneura resembles
      the previously studied highly polyphagous Estigmene acrea. Both arctiids are
      adapted to exploit pyrrolizidine alkaloid-containing plants as "drug sources".
      However, unlike E. acrea, G. geneura is not known to synthesize the pyrrolizidine
      derived male courtship pheromone, hydroxydanaidal, and differs distinctly in its
      metabolic processing of the plant-acquired alkaloids. Necine bases obtained from
      plant acquired pyrrolizidine alkaloids are re-esterified yielding two distinct
      classes of insect-specific ester alkaloids, the creatonotines, also present in E.
      acrea, and the callimorphines, missing in E. acrea. The creatonotines are
      preferentially found in pupae; in adults they are largely replaced by the
      callimorphines. Before eclosion the creatonotines are apparently converted into
      the callimorphines by trans-esterification. Open-chain ester alkaloids such as
      the platynecine ester sarracine and the orchid alkaloid phalaenopsine, that do
      not possess the unique necic acid moiety of the lycopsamine type, are sequestered
      by larvae but they need to be converted into the respective creatonotines and
      callimorphines by trans-esterification in order to be transferred to the adult
      stage. In the case of the orchid alkaloids, evidence is presented that during
      this processing the necine base (trachelanthamidine) is converted into its 7-(R)
      hydroxy derivative (turneforcidine), indicating the ability of G. geneura to
      introduce a hydroxyl group at C-7 of a necine base. The creatonotines and
      callimorphines display a striking similarity to plant necine monoesters of the
      lycopsamine type to which G. geneura is well adapted. The possible function of
      insect-specific trans-esterification in the acquisition of necine bases derived
      from plant acquired alkaloids, especially from those that cannot be maintained
      through all life-stages, is discussed.

PMID- 16102416
TI  - Molecular characterization and evolution of pheromone binding protein genes in
      Agrotis moths.
AB  - Pheromone-binding proteins (PBPs) are soluble transporter proteins that increase
      the capture and the solubilization of pheromone molecules in the lymph
      surrounding the olfactory receptors. A polymerase chain reaction-based method was
      used to identify PBP genes in Agrotis species for an evolutionary genomic study
      of noctuid moth PBPs. From genomic DNA we determined the structure of different
      PBP genes in the two closely related species, Agrotis ipsilon and A. segetum. In
      all, we clearly identified four genes (Aips-1, Aips-2, Aseg-1 and Aseg-2) that
      represent two distinct PBP orthology groups. We found that the four genes have
      the same exon-intron structure and that they comprise three exons and two introns
      but differ in length mainly in the second intron. The three exons of Aseg-2 and
      Aips-2 have the same lengths but both intron 1 and intron 2 differ in length
      between the genes. In contrast, Aips-1 and Aseg-1 show dissimilarity only in the
      length of intron 2. Interestingly, introns 1 and 2 are inserted in the same
      positions in the Aips-1, Aips-2, Aseg-1 and Aseg-2 genes. These findings show
      that the Agrotis PBP genes have common ancestry and probably originate from gene
      duplication before the speciation of ipsilon and segetum. We found that
      expression of Aips-1/Aseg-1 and Aips-2/Aseg-2 is antennal-specific, but
      expression is not restricted to the male antennae.

PMID- 16102417
TI  - The BmChi-h gene, a bacterial-type chitinase gene of Bombyx mori, encodes a
      functional exochitinase that plays a role in the chitin degradation during the
      molting process.
AB  - The silkworm, Bombyx mori, has been recently demonstrated to contain a bacterial
      type chitinase gene (BmChi-h) in addition to a well-characterized endochitinase
      gene (BmChitinase). The deduced amino acid sequence of BmChi-h showed extensive
      structural similarities with chitinases from bacteria such as Serratia marcescens
      chiA and baculoviruses (v-CHIA). Bacterial-type chitinase genes have not been
      found from any eukaryotes and viruses except for lepidopteran insects and
      lepidopteran baculoviruses. Thus, it was suggested that BmChi-h may be derived
      from a bacterial or baculovirus chitinase gene via horizontal gene transfer. In
      this report, we investigated the biological function of BmChi-h. Our
      enzymological study indicated that a chitinase encoded by BmChi-h has exo-type
      substrate preference, which is the same as S. marcescens chiA and v-CHIA, and
      different from BmChitinase, which has endo-type substrate preference. An
      immunohistochemical study revealed that BmChi-h localizes in the chitin
      containing tissues during the molting stages, indicating that it plays a role in
      chitin degradation during molting. These results suggest that BmChi-h
      (exochitinase) and BmChitinase (endochitinase) may catalyze a native chitin by a
      concerted mechanism. Cloning and comparison of BmChi-h orthologues revealed that
      bacterial-type chitinase genes are highly conserved among lepidopteran insects,
      suggesting that the utilization of a bacterial-type chitinase during the molting
      process may be a general feature of lepidopteran insects.

PMID- 16102418
TI  - Effect of chloroquine on the expression of genes involved in the mosquito immune
      response to Plasmodium infection.
AB  - Chloroquine has been described to increase Plasmodium infectivity to the mosquito
      vector and is known to affect the vertebrate host immune response including
      during malarial infection. Although knowledge of the mosquito immune response has
      recently improved, nothing is known about the impact of chloroquine on mosquito
      immunity. In order to characterize the influence of chloroquine on the mosquito
      immune system, we have analyzed the effect of chloroquine on Anopheles gambiae
      (i) serine proteases and (ii) antimicrobial peptide gene expression, in
      uninfected and Plasmodium berghei infected mosquitoes, using real-time PCR. We
      have demonstrated for the first time that mosquitoes fed on chloroquine-treated
      mice showed a significant down regulation of some immune-related genes. This
      effect was independent of midgut bacterial burden. These results suggest that
      chloroquine might act on the Anopheles serine proteases cascade, interfering with
      signal transduction pathways and at a transcriptional activation level.

PMID- 16102419
TI  - Accumulation of 23 kDa lipocalin during brain development and injury in
      Hyphantria cunea.
AB  - The cDNA corresponding to a novel lipocalin was identified from the fall webworm,
      Hyphantria cunea. This lipocalin cDNA encodes a 194 residue protein with a
      calculated molecular mass of 23 kDa. Sequence analyses revealed that the 23 kDa
      lipocalin cDNA is most similar to Drosophila lazarillo, human apolipoprotein D,
      and Bombyrin. Northern blot analyses showed that 23 kDa lipocalin transcript is
      expressed in the whole body only in 4- and 6-day-old pupae. By Western blot
      analysis it was confirmed that 23 kDa lipocalin is mainly accumulated in brain
      and subesophageal ganglion, though it is detected in a small amount in fat body
      and epidermis of Hyphantria cunea. The accumulation of 23 kDa lipocalin in brain
      tissue was upregulated in response to injury. The putative function of 23 kDa
      lipocalin in brain is discussed.

PMID- 16102420
TI  - The transcriptome of the salivary glands of the female western black-legged tick
      Ixodes pacificus (Acari: Ixodidae).
AB  - Sequencing of an Ixodes pacificus salivary gland cDNA library yielded 1068
      sequences with an average undetermined nucleotide of 1.9% and an average length
      of 487 base pairs. Assembly of the expressed sequence tags yielded 557 contigs,
      138 of which appear to code for secreted peptides or proteins based on
      translation of a putative signal peptide. Based on the BLASTX similarity of these
      contigs to 66 matches of Ixodes scapularis peptide sequences, only 58% sequence
      identity was found, indicating a rapid divergence of salivary proteins as
      observed previously for mosquito and triatomine bug salivary proteins. Here we
      report 106 mostly full-length sequences that clustered in 16 different families:
      Basic-tail proteins rich in lysine in the carboxy-terminal, Kunitz-containing
      proteins (monolaris, ixolaris and penthalaris families), proline-rich peptides, 5
      , 9.4- and 18.7-kDa proteins of unknown functions, in addition to
      metalloproteases (class PIII-like) similar to reprolysins. We also have found a
      family of disintegrins, named ixodegrins that display homology to variabilin, a
      GPIIb/IIIa antagonist from the tick Dermacentor variabilis. In addition, we
      describe peptides (here named ixostatins) that display remarkable similarities to
      the cysteine-rich domain of ADAMST-4 (aggrecanase). Many molecules were assigned
      in the lipocalin family (histamine-binding proteins); others appear to be
      involved in oxidant metabolism, and still others were similar to ixodid proteins
      such as the anticomplement ISAC. We also identified for the first time a
      neuropeptide-like protein (nlp-31) with GGY repeats that may have antimicrobial
      activity. In addition, 16 novel proteins without significant similarities to
      other tick proteins and 37 housekeeping proteins that may be useful for
      phylogenetic studies are described. Some of these proteins may be useful for
      studying vascular biology or the immune system, for vaccine development, or as
      immunoreagents to detect prior exposure to ticks. Electronic version of the
      manuscript can be found at.

PMID- 16102421
TI  - Development and characterization of a double subgenomic chikungunya virus
      infectious clone to express heterologous genes in Aedes aegypti mosquitoes.
AB  - Three full-length infectious cDNA clones based on the alphavirus chikungunya
      (CHIKV) were developed and characterized in vitro and in vivo. The full-length
      clone retained the viral phenotypes of CHIKV in both cell culture and in
      mosquitoes and should be a valuable tool for the study of virus interactions in
      an epidemiologically significant natural vector, Aedes aegypti. Two additional
      infectious clones were constructed that express green fluorescent protein (EGFP)
      in the midgut, salivary glands, and nervous tissue of Aedes aegypti mosquitoes
      following oral infection. The two constructs differed in the placement of the
      subgenomic promoter and the gene encoding EGFP. Viruses derived from the pCHIKic
      EGFP constructs (5' CHIKV EGFP and 3' CHIKV EGFP) expressed EGFP in 100% of the
      Ae. aegypti mosquitoes tested on days 7 and 14 post infection (p.i.). The 5'
      CHIKV EGFP disseminated to 90% of the salivary glands and nervous tissue by day
      14 p.i. Dissemination rates of this new viral vector exceeds those of previous
      systems, thus expanding the repertoire and potential for gene expression studies
      on this important vector species.

PMID- 16102422
TI  - Molecular cloning and analysis of a novel teratocyte-specific carboxylesterase
      from the parasitic wasp, Dinocampus coccinellae.
AB  - Teratocytes derived from the embryonic membrane (serosa) of parasitoids are
      released into the host hemocoel when the parasitoid eggs hatch, where they
      perform several functions during the post-embryonic stage. A full-length cDNA
      encoding a putative carboxylesterase was isolated from the teratocytes of
      Dinocampus coccinellae and was designated as teratocyte-specific carboxylesterase
      (TSC). It contained an open reading frame of 2571 bp coding for a protein of 857
      amino acids with a calculated molecular mass of 89 kDa. The deduced amino acid
      sequence had many structural features that are highly conserved among serine
      hydrolases including Ser, Glu and His as a catalytic triad, carboxylesterase type
      B (FGGNPNSVTLLGYSAG)/ lipase-serine (VTLLGYSAGA) active sites, and six N
      glycosylation sites. Interestingly, the mRNA encoding the TSC gene was expressed
      exclusively in teratocytes but not in the parasitoid larva or in the non
      parasitized host. Most notably, the TSC protein was distinguished by an insertion
      of 294 amino acids towards the N-terminal region and was flanked by
      carboxylesterase domains. Furthermore, sequence alignment and homology search
      revealed these additional amino acids to be unique to TSC and the insertion
      contributed significantly to its molecular mass resulting in a larger protein
      than other esterases. In addition to sequence analysis, the possible role of TSC
      in relation to the host (Coccinella septempunctata) and parasitoid (D.
      coccinellae) system is discussed.

PMID- 16102423
TI  - The extensible alloscutal cuticle of the tick, Ixodes ricinus.
AB  - The proteins in the distensible alloscutal cuticle of the blood-feeding tick,
      Ixodes ricinus, have been characterized by electrophoresis and chromatography,
      two of the proteins were purified and their total amino acid sequence determined.
      They show sequence similarity to cuticular proteins from the spider, Araneus
      diadematus, and the horseshoe crab, Limulus polyphemus, and to a lesser extent to
      insect cuticular proteins. They contain a conserved sequence region, which is
      closely related to the chitin-binding Rebers-Riddiford consensus sequence present
      in many insect cuticular proteins. Only a fraction of the alloscutal proteins can
      be readily dissolved, and the dissolved proteins are difficult to separate by
      electrophoresis and column chromatography. The insoluble fraction can only be
      dissolved after degradation to smaller peptides. The mixture of extractable
      proteins as well as hydrolysates of the insoluble fraction are fluorescent when
      exposed to ultraviolet light, and the fluorescence corresponds in excitation and
      emission maxima to the fluorescence of the rubber-like arthropodan protein,
      resilin, and to the amino acid dityrosine. Small amounts of dityrosine were
      obtained from ticks in the early phase of a blood meal when the cuticle weighs
      less than 4 mg; increasing amounts were obtained from animals in the initial
      period of feeding, during which the cuticular weight increases from 4 to 11 mg,
      whereas little increase in dityrosine content was observed during the final
      period of engorgement. Cuticle from fully distended ticks contains about 60-80
      nmole dityrosine per tick, corresponding to 2-3 microg/mg cuticle. It is
      suggested that the major part of the cuticular proteins is made inextractable by
      cross-linking by dityrosine residues, and that dityrosine plays a role in
      stabilizing the cuticular structure during the extensive distension occurring
      during a blood meal. Small amounts of 3-monochlorotyrosine and 3,5
      dichlorotyrosine were obtained from the distended tick cuticle, corresponding to
      chlorination of between 0.5% and 1.5% of the tyrosine residues. It is suggested
      that the chlorotyrosines are a side-product of oxidative processes in the
      cuticle.

PMID- 16102424
TI  - Uptake and turn-over of glucosinolates sequestered in the sawfly Athalia rosae.
AB  - Larvae of the sawfly Athalia rosae sequester glucosinolates from their various
      host plants of the Brassicaceae into their hemolymph for defensive purposes. We
      found that the glucosinolate concentration in the insect varies in a fluctuating
      manner during larval development. Analyses of larvae which had been offered diets
      with different glucosinolate profiles showed that there is an equilibrium between
      a rapid uptake of glucosinolates into the hemolymph and a continuous turn-over.
      Injection of glucotropaeolin into the hemolymph and ingestion of the same amount
      resulted in similar levels of intact glucosinolates recovered from larvae after
      different periods of time. This indicates that hemolymph glucosinolates are the
      principal source for glucosinolate degradation. Feeding experiments with [14C]
      labeled glucotropaeolin revealed that the majority of the ingested glucosinolate
      is excreted as one or more unidentified metabolite(s) within 14 h. We found no
      indication for the presence of an insect myrosinase, or sulfatase in A. rosae,
      which have been shown to be involved in glucosinolate metabolism in other
      specialists feeding on Brassicaceae. Furthermore, the metabolism of sinalbin in
      A. rosae seems to result in different products than its metabolism in the
      caterpillar Pieris rapae. Obviously, A. rosae has yet another way of coping with
      the glucosinolates.

PMID- 16102425
TI  - Mutant Mos1 mariner transposons are hyperactive in Aedes aegypti.
AB  - The development of genetic strategies to control the spread of mosquito-borne
      diseases through the use of class II transposons has been hampered by suboptimal
      rates of transformation and the absence of post-integration mobility for all
      transposons evaluated to date. Two Mos1 mariner transposase mutants were produced
      by the site-directed mutagenesis of amino acids, E137 and E264, to K and R,
      respectively. The effects of these mutations on the transpositional activities of
      Mos1-derived transposon constructs were evaluated by interplasmid transposition
      assays in Escherichia coli and Aedes aegypti. The transpositional activities of
      two Mos1 transposons, one with imperfect wild type inverted terminal repeats
      (ITRs) and another that contained two perfectly matched 3' ITRs, were increased
      when the mutant transposases were supplied in trans in E. coli. The use of the
      perfect repeat transposon with wild type transposase did not result in an
      increase in transposition frequency in Ae. aegypti. However, an improvement in
      the integrity of the transposition process did occur, as evidenced by a lower
      rate of recombination events in which the transgene was transferred. An increase
      in the transpositional activity of the perfect repeat transposon was observed in
      the mosquito in the presence of either mutant transposase, and in the case of the
      E264R transposase, the observed increase in transposition frequency was also
      accompanied by a further improvement in the integrity of transposition. We
      discuss the possible contributions of these mutant residues to the transposition
      of the perfect repeat Mos1 transposon, the implications of these results with
      respect to the molecular evolution of Mos1, and the potential uses of the perfect
      repeat transposon and mutant transposases for the improvement of Mos1 mediated
      germ line transformation of Ae. aegypti.

PMID- 16102426
TI  - Scientific Registry of the International Society for Heart and Lung
      Transplantation: introduction to the 2005 annual reports.

PMID- 16102427
TI  - Registry of the International Society for Heart and Lung Transplantation: twenty
      second official adult heart transplant report--2005.

PMID- 16102428
TI  - Registry of the International Society for Heart and Lung Transplantation: twenty
      second official adult lung and heart-lung transplant report--2005.

PMID- 16102429
TI  - Registry of the International Society for Heart and Lung Transplantation: eighth
      official pediatric report--2005.

PMID- 16102430
TI  - Comparison of survival by allocation to medical therapy, surgery, or heart
      transplantation for ischemic advanced heart failure.
AB  - BACKGROUND: To ascertain survival of ischemic advanced heart failure patients by
      treatment allocation, we examined the outcome of transplant assessment patients
      allocated to medical therapy, high-risk conventional surgery, or transplantation.
      METHODS: Patients were identified from the Papworth transplant database and
      excluded if primary etiology was not ischemic. Grouping was undertaken according
      to treatment allocation at initial assessment, and analysis was performed by
      intention to treat. Survival was computed from the time of assessment and Cox
      regression used to stratify patients according risk with the Heart Failure
      Survival Score. RESULTS: From May 1993 to September 2001, a total of 755 patients
      were admitted for transplant assessment, with 348 (46.1%) identified as having
      heart failure of ischemic origin. Variables required for calculation of the Heart
      Failure Survival Score was available in 273 patients (78.4%), and 20 patients
      (7.3%) were lost to follow-up. Of the remaining 253 patients, 89 (35.2%) were
      allocated to medical therapy, 32 (12.6%) to surgery, and 132 (52.2%) to
      transplantation. The relative risk (95% confidence limit) of death compared with
      medical therapy was 0.62 (0.28, 1.40) for surgery and 0.38 (0.24, 0.61) for
      transplantation in medium- to high-risk patients. For low-risk patients, the
      relative risks for death compared with medical therapy were 1.87 (0.63, 5.60) for
      surgery and 1.97 (0.79, 4.96) for transplantation. CONCLUSIONS: Transplantation
      improved survival of medium- and high-risk patients compared with medical
      therapy. In the low-risk group, this was not evident. However, repeated
      assessment of risk is required because the hazard for death rises steadily after
      the third year in these patients.

PMID- 16102431
TI  - Effect of oral vitamin E and C therapy on calcineurin inhibitor levels in heart
      transplant recipients.
AB  - BACKGROUND: A recent prospective trial demonstrated that oral vitamins C and E
      retard the early progression of transplant-associated coronary arteriosclerosis;
      as a result, a number of centers have added these agents to their maintenance
      regimens. This study reviewed the impact of vitamin E and C supplementation on
      calcineurin inhibitor trough concentrations. METHODS: A retrospective chart
      review of the first 29 heart transplant patients prescribed anti-oxidant agents
      was performed. Twenty-two patients taking cyclosporin A (CsA) and 7 patients
      taking tacrolimus were prescribed vitamin C (500 mg twice a day) and vitamin E
      (400 IU twice a day). Serum chemistries and drug levels were measured before and
      after vitamin therapy was initiated. RESULTS: The baseline CsA trough
      concentration (mean +/- SD) was 137 +/- 39 ng/ml and it declined to 99 +/- 54
      ng/ml (p = 0.007) after anti-oxidant therapy was initiated. The average
      percentage decrease in the CsA trough concentration was 30%. No significant
      changes were seen in the patients taking tacrolimus. CONCLUSIONS: These data
      demonstrate that supplementation with the anti-oxidant agents vitamin C and
      vitamin E decreases CsA concentrations but does not appear to effect tacrolimus
      concentrations. Although more detailed pharmacokinetic analysis is necessary to
      clarify the exact mechanism of this interaction, physicians who take care of
      transplant recipients should be aware that more frequent CsA concentration
      monitoring is warranted after initiating these anti-oxidant agents.

PMID- 16102432
TI  - Prostate cancer after heart transplantation: unicenter case-control study.
AB  - BACKGROUND: We have noted an unexpectedly high incidence of prostate cancer in
      our heart transplant recipients (HTR). METHODS: We conducted a retrospective
      review of patients after heart transplantation to investigate the prevalence,
      treatment, and outcome of prostate cancer diagnosed after systematic screening
      (study group). We compared them with case-matched HTR (control). RESULTS: Among
      702 recipients, 15 patients had elevated prostate-specific antigen (PSA) levels.
      Fourteen cases of prostate cancer were diagnosed and treated. The median time
      between transplantation and prostate cancer diagnosis was 73 months. No patient
      was diagnosed in a locally advanced (>T2) or metastatic stage. Eleven patients
      (78.6%) received curative treatment. During follow-up (median, 44 months), 1
      patient died from prostate cancer. The survival rate between the study and
      control groups did not differ. CONCLUSION: Routine PSA testing is recommended as
      a screening test for prostate cancer in patients after heart transplantation. We
      believe this could also result in detection of early stages of prostate cancer,
      thus allowing curative treatment, and achieving similar survival to other case
      matched HTR with no prostate cancer.

PMID- 16102433
TI  - Mild vs severe pulmonary hypertension before heart transplantation: different
      effects on posttransplantation pulmonary hypertension and mortality.
AB  - BACKGROUND: Pulmonary hypertension (PH) is common in severe heart failure, but
      the effect of mild PH on posttransplantation PH and survival after heart
      transplantation has not been well described. METHODS: This cohort study examined
      preoperative and postoperative hemodynamics in 172 heart transplant recipients at
      Johns Hopkins Hospital followed for up to 15.1 years. PH was defined as pulmonary
      vascular resistance > or =2.5 Wood units, as measured during routine right heat
      catheterization; mild to moderate PH was defined as PVR between 2.5 and 4.9 Wood
      units; and severe PH was defined as PVR > or =5.0 Wood units. RESULTS: Seventy
      one patients (41.3%) had PH, mostly of mild/moderate severity (77.5%), at the
      last routine hemodynamic monitoring before transplantation (median time before
      transplantation, 2.7 months). During follow-up, 105 patients (62.9%) developed PH
      at some point after transplantation, and 48 patients died (cumulative incidence,
      76.5%). Mild/moderate preoperative PH was associated with increased risk of
      posttransplantation PH at 1, 3, and 6 months, but not with later episodes of PH.
      Mild/moderate preoperative PH was not associated with a higher mortality rate,
      but each 1 Wood unit increase in preoperative PVR demonstrated a trend toward
      increased mortality. Severe preoperative PH was associated with death within the
      first year after adjusting for potential confounders, but not with overall
      mortality or mortality at other time points. CONCLUSIONS: Mild to moderate
      preoperative PH is associated with increased risk of developing early but not
      late posttransplantation PH and may suggest different management strategies.
      Although PH was not consistently associated with mortality, increasing severity
      of the preoperative PH suggests potentially worse prognosis.

PMID- 16102434
TI  - Safety and efficacy of rosuvastatin therapy for the prevention of hyperlipidemia
      in adult cardiac transplant recipients.
AB  - BACKGROUND: Hyperlipidemia after orthotopic heart transplantation (OHT) is
      associated with immunosuppression. Many OHT patients have increased lipid levels
      above published guidelines despite treatment with high doses of statins.
      Treatment with rosuvastatin (ROS) in OHT patients has not yet been evaluated.
      Therefore, we assessed its efficacy and safety in an OHT population. METHODS:
      Twenty-one OHT recipients, median age 66 years, whose lipid levels were sub
      optimal on the highest tolerated doses of statins, received ROS in addition to
      standard immunosuppression. Total cholesterol (TC), low-density lipoprotein (LDL
      C) and high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), liver
      transaminases (AST) and creatinine kinase (CK) were measured before and during
      treatment with ROS. RESULTS: After 6 weeks on an average ROS dose of 10 mg/day, a
      TC:HDL-C ratio of <4 was reached in 76% of patients, and 70% of patients reached
      an LDL-C level of <2.5 mmol/liter (100 mg/dl). TC decreased to <5.2 mmol/liter
      (200 mg/dl) in 80% of patients and TG decreased to <2 mmol/liter (175 mg/dl) in
      61% of patients. Except for the HDL-C increase, all changes were statistically
      significant. The decrease in the median TC:HDL-C ratio between baseline and 6
      weeks was also statistically significant (p = 0.001). There were no significant
      changes in CK or AST levels, and no clinical evidence of myositis. One patient
      developed myalgia and 2 were withdrawn from the study because of mild elevation
      of CK (<3-fold upper limit of normal [ULN]). CONCLUSIONS: In the setting of
      tertiary referral centers, ROS appears to be safe and effective in lowering LDL-C
      in OHT recipients in whom treatment with other statins failed to achieve target
      LDL-C. No evidence of liver or muscle dysfunction was noted. Long-term studies
      are needed to ascertain the effect of ROS therapy on incidence of coronary artery
      disease (CAD) in this population.

PMID- 16102435
TI  - Systemic activation of integrin alphaVbeta3 in donors with spontaneous
      intracerebral hemorrhage is associated with subsequent development of
      vasculopathy in the heart transplant recipient.
AB  - BACKGROUND: Recipients of hearts from donors with spontaneous intracerebral
      hemorrhage (ICH) are at increased risk of allograft vasculopathy compared with
      trauma donors. We have recently shown that the vitronectin receptor (integrin
      alpha(V)beta3) is upregulated in transplant vasculopathy. We hypothesized that
      donor ICH is associated with systemic activation of alpha(V)beta3 in the donor
      before transplantation. METHODS: We evaluated mRNA expressions of alpha(V)beta3
      (TaqMan PCR) in endomyocardial biopsy samples at 1-week post-transplant in 20
      recipients from ICH donors and 20 recipients from trauma donors. To investigate
      whether systemic activation of alpha(V)beta3 was present in the donor before
      transplantation, alpha(V)beta3 expression was also evaluated in the corresponding
      donor spleen lymphocytes. All patients underwent serial coronary intravascular
      ultrasound to evaluate for coronary vasculopathy. The baseline characteristics
      were similar except for increased donor age in the ICH Group. RESULTS: The ICH
      Group showed significant increased mRNA expression of alpha(V)beta3 in the heart
      biopsy samples (3.8-fold, p = 0.012) and in the corresponding donor spleen
      lymphocytes (3.5-fold, p = 0.014) compared with the Trauma Group. At 1 year, the
      ICH Group also showed increased progression of coronary vasculopathy.
      Multivariate regression analysis found that donor lymphocytic alpha(V)beta3 mRNA
      expression was independently associated with increased risk of vasculopathy (odds
      ratio, 1.9; 95% CI, 1.21-3.98, p = 0.03). CONCLUSIONS: Our report demonstrates
      the presence of systemic activation of alpha(V)beta3 in donors with spontaneous
      intracerebral hemorrhage and its association with the subsequent development of
      allograft vasculopathy in the recipient.

PMID- 16102436
TI  - Relationship among epicardial coronary disease, tissue myocardial perfusion, and
      survival in heart transplantation.
AB  - BACKGROUND: Cardiac allograft vasculopathy continues to represent the major
      limitation to long-term cardiac allograft survival. Routine angiography and
      intravascular ultrasound fall short in their ability to detect microcirculatory
      aberrations. Thrombolysis in myocardial infarction (TIMI) myocardial perfusion
      grades (TMPG) have been used as a measure of microvascular circulation in
      patients treated for acute myocardial infarction. We studied the correlation of
      epicardial coronary anatomy with microvascular flow as determined by TMPG and
      correlated it with patient outcome. METHODS: We enrolled 66 consecutive cardiac
      transplant recipients (49 men; mean age 52 +/- 13 years; range 15-70 years)
      undergoing surveillance coronary angiogram during a 9-month period. All
      angiograms were interpreted for epicardial coronary anatomy by an independent
      investigator. Another investigator, blinded for clinical data and angiogram
      interpretation, interpreted TMPGs. TMPG 0 was defined as no apparent tissue-level
      perfusion; TMPG 1 indicated presence of myocardial blush but no clearance from
      the microvasculature; TMPG 2 blush cleared slowly; and TMPG 3 indicated that
      blush began to clear during washout (blush is minimally persistent after 3
      cardiac cycles of washout). Cardiac deaths served as the primary outcome
      variable. RESULTS: Fifty-eight of 66 patients had an abnormal TMPG. Mean TMPG in
      all these patients was 4.2 +/- 3 (normal is 9). Forty-four patients (Group A)
      with no angiographic coronary narrowing had TMPG 4.81 +/- 3.1, and 22 patients
      (Group B) with epicardial coronary narrowing 40% of lumen diameter had TMPG 3.0
      +/- 2.5 (p = 0.007). There was no difference in TMPG related to the coronary
      territory involved. At a mean follow-up of 30 +/- 2.5 months, 6 (13.6%) of 44
      patients in Group A had died, and 7 (31.8%) of 22 in Group B had died (p < 0.03).
      CONCLUSIONS: Microcirculatory aberrations as assessed by tissue TMPG is abnormal
      across all coronary territories in cardiac transplant recipients and associated
      with poor survival, suggesting a generalized microvascular involvement even in
      the presence of a normal angiogram. Patients with focal epicardial coronary
      narrowing have significantly greater decline in tissue perfusion, independent of
      the coronary territory involved, and exhibit poor survival compared with patients
      without epicardial coronary disease.

PMID- 16102437
TI  - Inflammatory response and re-stenosis after percutaneous coronary intervention in
      heart transplant recipients and patients with native atherosclerosis.
AB  - BACKGROUND: The clinical benefit of percutaneous coronary intervention (PCI) in
      heart transplant recipients (HTRs) with coronary allograft vasculopathy (CAV) has
      been questioned. We investigated the degree of inflammatory reaction during PCI
      in CAV compared to patients with native atherosclerosis, and the possible
      relationship between PCI-induced inflammation and the degree of re-stenosis in
      these 2 patient groups. METHODS: In 11 CAV patients and 10 patients with native
      atherosclerosis, blood samples were drawn before and 24 hours and 6 months after
      PCI, and analyzed with regard to hsCRP, MCP-1, components of complement
      activation, von Willebrand factor (vWf), soluble L-selectin and ICAM-1.
      Quantitative angiography was performed before and after PCI, and at 6-month
      follow-up. RESULTS: Baseline levels of hsCRP, vWf and MCP-1 were significantly
      elevated and levels of L-selectin and ICAM-1 and activation products of the
      alternative pathway of the complement system were decreased in CAV patients
      compared to those with native atherosclerosis. PCI induced significant increases
      of hsCRP in both groups as well as an increase in vWf in native atherosclerosis,
      whereas a decrease in L-selectin was observed in native atherosclerosis. Plasma
      levels of MCP-1 correlated with percent stenosis at follow-up in both groups,
      whereas a correlation between hsCRP and percent stenosis was evident only in
      patients with native atherosclerosis. There were no differences in rates of re
      stenosis between the 2 groups. CONCLUSIONS: HTRs with CAV and patients with
      native atherosclerosis are characterized by different profiles of immune
      activation and respond differently to PCI. Nevertheless, an inappropriate
      inflammatory reactivity may predispose to re-stenosis after PCI in both groups of
      patients, with pre-procedural inflammation being of particular importance in CAV.

PMID- 16102438
TI  - The effect of combined Angiotensin-converting enzyme inhibition and calcium
      antagonism on allograft coronary vasculopathy validated by intravascular
      ultrasound.
AB  - BACKGROUND: Hypertension is a potential risk factor for allograft coronary
      vasculopathy. We evaluated the efficacy of angiotensin-converting enzyme (ACE)
      inhibitors and calcium antagonists, and their combined use, on the development of
      coronary vasculopathy in hypertensive heart transplant recipients. METHODS:
      Eighty-two heart transplant recipients underwent serial intravascular ultrasound
      (IVUS) analysis at baseline (within 1 month) and at 1 year after transplantation
      and were evaluated for the development of coronary vasculopathy. Patients were
      divided into 4 groups. Nineteen normotensive recipients received no treatment,
      control (Group A). Hypertensive patients were treated with either ACE inhibitors
      (Group B, n = 37), calcium antagonists (Group C, n = 16), or both (Group D, n =
      10). RESULTS: We found a significant reduction in IVUS indices of coronary
      vasculopathy in heart transplant recipients who used a combination of an ACE
      inhibitor and a calcium antagonist compared with recipients who used either drug
      alone (p < 0.05). This synergistic efficacy was independent of the baseline
      indices evaluated in a multivariate regression analysis model and was noted
      despite comparable mean arterial pressure among the 3 hypertensive groups at 1
      year, thus suggesting the presence of a synergistic anti-proliferative effect
      beyond the anti-hypertensive efficacy. CONCLUSIONS: The combined use of an ACE
      inhibitor and a calcium antagonist is more effective than the individual use of
      either drug alone on the development of coronary vasculopathy in cardiac
      transplant recipients. Large randomized clinical trials are warranted to evaluate
      such a synergistic efficacy.

PMID- 16102439
TI  - Neointimal inflammation and adventitial angiogenesis correlate with severity of
      cardiac allograft vasculopathy in pediatric recipients.
AB  - BACKGROUND: Chronic inflammation and angiogenesis have been implicated in the
      pathogenesis of both cardiac allograft vasculopathy (CAV) and age-related
      vasculopathy. Because concurrent atherosclerosis does not complicate assessment
      of CAV in children, we sought to characterize the spectrum of coronary lesions in
      this population and determine whether inflammatory infiltrates and angiogenesis
      correlate with severity of CAV. METHODS: In 18 pediatric heart specimens CAV was
      graded 1 to 4 (none to severe). Each case was assigned to either: Group I, no
      inflammation; Group II, perivascular inflammation; or Group III, perivascular and
      neointimal inflammation. Inflammatory infiltrates were immunophenotyped using
      anti-CD3, anti-CD20 and HAM 56. Angiogenesis was assessed by determining
      microvascular density (MVD) in 5 high-power fields (HPFs) per section. RESULTS:
      CAV was evident in 94% of cases, and inflammation in 61%. Cases with neointimal
      inflammation had significantly more severe CAV compared with cases without
      inflammation (2.7 +/- 0.16 vs 1.9 +/- 0.2, p = 0.002). MVD was significantly
      higher in both inflammation groups (Groups II and III) compared with Group I (4.1
      +/- 0.5 per HPF and 5.9 +/- 0.5 vs 3.1 +/- 0.7, p = 0.018 and p = 0.002) and
      correlated with the degree of CAV (p = 0.007). The perivascular infiltrates
      (Group II, n = 5) contained lymphocytes, macrophages and plasma cells, and 67% of
      neointimal infiltrates (Group III, n = 6) also contained eosinophils.
      CONCLUSIONS: CAV in children is more common than previously reported. Our data
      indicate that CAV is often associated with inflammation and that adventitial
      angiogenesis correlated with the severity of CAV.

PMID- 16102440
TI  - Neuroendocrine profiling of humans receiving cardiac allografts.
AB  - BACKGROUND: Several studies have investigated changes in circulating hormones and
      markers of cardiac status after heart transplantation in humans. As a result,
      plasma levels of various hormones and autocoids have been associated with cardiac
      allograft rejection status. However, no clear associations can be defined given
      the highly contradictory nature of the available literature. METHODS: In this
      study of 69 consecutive heart transplant patients followed for >2 years we
      examine the relationship between neurohumors potentially related to allograft
      rejection and endomyocardial biopsy grade of rejection (according to the ISHLT)
      and hemodynamic status. Markers assessed include brain natriuretic peptide (BNP),
      amino-terminal pro-BNP (N-BNP), atrial natriuretic factor (ANF), adrenomedullin,
      interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, troponin C and C
      reactive protein. RESULTS: The highest plasma levels for most neurohumors were
      found shortly after surgery and showed a trend towards normalization with time.
      BNP and N-BNP were the only significantly elevated plasma analytes for patients
      with Grade 3 rejection as compared with other ISHLT grades. ANF plasma levels
      correlated with BNP and N-BNP in Grades 0 to 2, but not in Grade 3, suggesting
      that in this rejection grade the usual coordinated changes observed in BNP and
      ANF secretion no longer exist. Cardiac filling pressures were correlated with
      plasma BNP, N-BNP and ANF levels only for Grades 0 and 1. CONCLUSIONS: The timing
      of blood sampling after transplantation influences the level of the neurohumors
      measured, which may help explain the conflicting literature reports on the
      association between neurohumor levels and rejection grade. The significant
      increase in circulating levels of BNP and N-BNP observed in most cases of Grade 3
      rejection occurred with no apparent relationship to post-transplantation time,
      which suggests a specific influence of acute rejection on BNP gene expression.

PMID- 16102441
TI  - Transcript signatures of lymphocytic bronchitis in lung allograft biopsy
      specimens.
AB  - BACKGROUND: Rejection and obliterative bronchiolitis are barriers to sustained
      graft function in recipients of transplanted lungs. Early detection is hindered
      by inadequate tests and an incomplete understanding of the molecular events
      preceding or accompanying graft deterioration. METHODS: Hypothesizing that genes
      involved in immune responses and tissue remodeling produce biomarkers of
      rejection, we measured the expression of 192 selected genes in 72 sets of biopsy
      specimens from human lung allografts. Gene transcripts were quantified using a 2
      step, multiplex, real-time polymerase chain reaction approach in endobronchial
      and transbronchial biopsy specimens from transplant recipients without acute
      infections undergoing routine surveillance bronchoscopy. RESULTS: Comparisons of
      histopathology in parallel biopsy specimens identified 6 genes correlating with
      rejection as manifested by lymphocytic bronchitis, a suspected harbinger of
      obliterative bronchiolitis. For example, beta2-defensin and collagenase
      transcripts in inflamed bronchi increased 37-fold and 163-fold, respectively. By
      contrast, these transcripts did not correlate with acute rejection in
      transbronchial specimens. Further, no correspondence was noted between
      histopathologic bronchitis and parenchymal rejection when endobronchial and
      transbronchial samples were obtained from the same patient. CONCLUSIONS: Our
      highly sensitive method permits quantitation of many gene transcripts
      simultaneously in small, bronchoscopically acquired biopsy specimens of
      allografts. Transcript signatures obtained by this approach suggest that airway
      and alveolar responses to rejection differ and that endobronchial biopsy
      specimens assess lymphocytic bronchitis and chronic rejection but are not proxies
      for transbronchial biopsy specimens. Further, they reveal changes in airway
      expression of the specific genes involved in host defense and remodeling and
      suggest that the measurement of transcripts correlating with lymphocytic
      bronchitis may be diagnostic adjuncts to histopathology.

PMID- 16102442
TI  - Upregulation of CD40, CD80, CD83 or CD86 on alveolar macrophages after lung
      transplantation.
AB  - BACKGROUND: Alveolar macrophages (AMs) are known to be poor antigen-presenting
      cells, and lack the accessory molecules such as CD40, CD80 or CD86 to activate T
      cells. The question raised is about the potential changes in phenotypes after
      lung transplantation, particularly during acute rejection episodes. METHODS: The
      present study analyzed the phenotype of AMs longitudinally in 45 lung transplant
      patients, between August 1997 and April 2002, with a follow-up period of 27.2 +/-
      2.5 (mean +/- SEM) months. There were 7.7 +/- 0.6 bronchoalveolar lavage (BAL)
      assessments performed per patient (i.e., 345 BALs), simultaneously with
      transbronchial biopsies. Transplantation was soon followed by a progressive
      upregulation of CD40 on 49.7 +/- 8% of AMs during the first month, and this
      marker remained elevated at 60 +/- 8% after 5 years. RESULTS: Both CD86 and CD80,
      as well as CD83, a marker of dendritic cells, were enhanced for most AMs during
      Grade A2 and A3 rejection episodes. A correlation was found between expression of
      CD83 and CD86, but not between CD1a and CD86. Immunohistology confirmed that CD40
      positive cells in the alveoli corresponded to AMs and to some dendritic cells in
      the basal layers of the airways. In vitro studies showed that harvested AMs with
      these enhanced accessory molecules remained poor stimulators of allogeneic cells,
      a phenomenon that may be related to the ongoing immunosuppressive treatments.
      CONCLUSIONS: AM phenotypes showed marked changes during early or late acute
      rejection episodes, acquiring CD80, CD83 and CD86, while CD40 expression was
      further enhanced. This finding may provide clues on how to monitor the tolerance
      of transplanted lungs and may also provide new insights into the pathophysiology
      of lung transplantation.

PMID- 16102443
TI  - Monitoring C2 level predicts exposure in maintenance lung transplant patients
      receiving the microemulsion formulation of cyclosporine (Neoral).
AB  - BACKGROUND: Dosing of the microemulsion formulation of cyclosporine (Neoral) is
      conventionally based on trough levels (C(0)). However, experience in renal
      transplantation has shown that cyclosporine exposure during the absorption phase
      (AUC(0-4)) is critical for optimizing immunosuppression, and that cyclosporine
      (CsA) concentration at 2 hours post-dose (C(2)) shows the closest correlation
      with AUC(0-4). This study evaluated whether C(2) values correlate more closely
      with AUC(0-4) than C(0) in lung transplant patients. METHODS: Pharmacokinetic
      data were collected prospectively from 20 clinically stable adult lung allograft
      recipients receiving CsA, mycophenolate mofetil and steroids. Indications for
      transplantation were emphysema (n = 15), idiopathic fibrosis (n = 2), primary
      pulmonary hypertension (n = 1), cystic fibrosis (n = 1) and
      lymphangioleiomyomatosis LAM (n = 1). Blood samples were collected at 0, 1, 2, 3
      and 4 hours after administration of CsA, and then AUC(0-4) was calculated. The
      Correlation between cyclosporine concentration at each time-point and AUC(0-4)
      was also calculated. RESULTS: C(2) showed the closest correlation with AUC(0-4)
      (r(2) = 0.85). C(0) had the poorest correlation of all time-points (r(2) = 0.64).
      Two patients with radiologic signs of gastroparesis had no peak cyclosporine
      levels at all and were excluded from the correlation analysis. Mean AUC(0-4) was
      3,700 ng . h/ml during Year 1 post-transplant, 2,400 ng . h/ml during Years 1 to
      3, and 1,500 ng . h/ml thereafter. Mean C(2) values were 1.2 microg/ml during
      Year 1, 0.8 microg/ml during Years 1 to 3, and 0.5 microg/ml thereafter.
      CONCLUSIONS: C(2) is the single time-point that correlates most closely with
      AUC(0-4) in lung transplant recipients without gastroparesis. It remains to be
      demonstrated whether monitoring CsA based on C(2) levels results in a lower
      incidence of rejection without additional toxicity.

PMID- 16102444
TI  - Experimental lung transplantation: impact of preservation solution and route of
      delivery.
AB  - BACKGROUND: Optimal preservation of allograft integrity is essential to reduce
      post-ischemic organ dysfunction after lung transplantation. Retrograde organ
      preservation leads to homogeneous intrapulmonary distribution and eliminates
      intravascular thrombi. So far, no comparative studies exist with regard to
      preservation quality following retrograde preservation with Perfadex and Celsior
      after extended cold-ischemia intervals. METHODS: In an in vivo pig model, 5 lungs
      each were preserved for 27 hours using antegrade or retrograde perfusion
      techniques with Celsior (Ce(ant)/CE(ret)) and Perfadex (PER(ant)/PER(ret)). After
      left lung transplantation and contralateral lung exclusion, hemodynamics,
      oxygenation and dynamic compliance were monitored for 6 hours and compared with
      sham-operated controls. Pulmonary edema was determined stereologically.
      Statistics consisted of analysis of variance (ANOVA) with repeated measures.
      RESULTS: Mortality of all Celsior-protected lungs was 100% due to severe
      reperfusion injury with profound lung edema. In contrast, organ preservation with
      PER(ant) led to sufficient graft function without mortality. Preservation quality
      after retrograde administration of Perfadex resulted in optimized oxygenation
      capacity compared with PER(ant) (p = 0.046). Furthermore, intra-alveolar edema
      was reduced and generally comparable with sham controls. In general, retrograde
      preservation led to continuous washout of small blood and fibrin clots from the
      pulmonary capillary system. CONCLUSIONS: Perfadex solution provided sufficient
      lung preservation for 27 hours of cold ischemia, and its retrograde application
      led to significant functional and histologic improvement compared with antegrade
      perfusion. In contrast, preservation with Celsior solution resulted in lethal
      post-ischemic outcome, regardless of the route of administration, and therefore
      must be considered unsuitable for extended lung procurement.

PMID- 16102445
TI  - Construction of a unidirectionally beating 3-dimensional cardiac muscle
      construct.
AB  - BACKGROUND: Cardiac tissue engineering aims to construct cardiac tissue with
      characteristics similar to those of the native tissue. Engineered cardiac tissues
      (ECTs) can be constructed using synthetic scaffold or liquid collagen. We report
      an initial study using our own newly designed cardiac muscle device to construct
      heart tissue. We investigated the effects of cell seeding density and collagen
      quantity on the formation of liquid collagen-based cardiac muscle. METHODS: We
      obtained cardiac myocytes from neonatal rats mixed with collagen type I and
      matrix factors cast in circular molds to form circular strands. Cell densities
      (0.1 x 10(7) to 6 x 10(7)) and collagen quantity (0.3 to 1.0 ml/ECT) were tested.
      Cell gross morphology, cell orientation, spatial distribution and ultrastructure
      were evaluated using histologic analyses, confocal laser scanning microscopy and
      transmission electron microscopy. RESULTS: Histologic analyses of ECTs revealed
      that cardiac cells reconstituted longitudinally oriented, cardiac bundles with
      morphologic features characteristic of the native tissue. Confocal and electron
      microscopy demonstrated that, using optimized cell density and collagen quantity,
      we made ECTs with characteristic features similar to those of native
      differentiated myocardium. CONCLUSIONS: ECTs comparable to native cardiac tissue
      can be engineered under optimized conditions. This construct is a first step in
      the development of cardiac tissue engineered in vitro, and may be used as a basis
      for studies of cardiac development, drug testing and tissue replacement therapy.

PMID- 16102446
TI  - Lung transplantation from out-of-hospital non-heart-beating lung donors. one-year
      experience and results.
AB  - There is currently no method for preservation and functional evaluation of
      clinical out-of-hospital non-heart-beating lung donors (NHBLD) that can be
      applied practically and systematically in clinical lung transplantation programs.
      A new method of preservation and functional evaluation of the lung has been
      developed in NHBLD that is based on the knowledge of various experimental
      studies. Initially, the viability of lungs harvested this way was proved from
      preliminary functional and histologic tests. In November 2002, we started using
      lung allografts from non-heart-beating donors. Five lung transplantations (4
      bipulmonary and 1 unipulmonary) were performed successfully. The short and mid
      term results have been excellent and all recipients are alive. We report our
      initial experience, which we hope will be of help to those involved in clinical
      lung transplantation programs worldwide.

PMID- 16102447
TI  - Transplantation for myocarditis: a controversy revisited.
AB  - Myocarditis is a major cause of end-stage heart failure and is responsible for up
      to 10% of cases of idiopathic dilated cardiomyopathy (IDC). Worldwide,
      approximately 45% of all heart transplants are performed for IDC and up to 8% for
      myocarditis. Early reports suggested that survival after transplantation for
      myocarditis was poor and patients had an increased risk of rejection. More
      recently, larger case series suggest that overall survival after transplantation
      for myocarditis is similar to survival after transplantation for other causes.
      However, certain disorders, including cardiac sarcoidosis and giant cell
      myocarditis (GCM), require heightened surveillance for post-transplantation
      disease recurrence. We present the case of a 42-year-old man with recurrence of
      GCM 8 years after transplantation and review the literature on the role of
      cardiac transplantation for patients with myocarditis.

PMID- 16102448
TI  - It is time to stop ignoring malignancy in heart transplantation: a call to arms.
AB  - Increasing numbers of patients are surviving more than 5 years after heart
      transplantation. Despite the dramatic nature of coronary allograft vasculopathy,
      Cardiac Transplant Research Database data have shown, and International Society
      for Heart and Lung Transplantation Registry data suggest, that malignancy is the
      leading cause of death among long-term survivors of heart transplantation.
      Recommendations on malignancy screening are provided as well as an outline of
      areas of ongoing uncertainty.

PMID- 16102449
TI  - Effect of short-term treatment with pravastatin on cytokines and cytokine
      receptors in patients with chronic heart failure due to ischemic and nonischemic
      disease.
AB  - The antiinflammatory effect of lipoproteins through neutralization of circulating
      endotoxin has questioned the safety of lipid-lowering drugs in chronic heart
      failure (CHF). We measured serum levels of interleukin-6, tumor necrosis factor
      (TNF)-alpha, and soluble TNF-alpha receptors 1 and 2 before and after 1-month
      treatment with pravastatin 40 mg in 58 patients with CHF. Short-term treatment
      with pravastatin attenuated the immune response in patients with CHF due to
      ischemic or nonischemic etiology.

PMID- 16102450
TI  - Promotion of long-term heart allograft survival by combination of mobilized donor
      plasmacytoid dendritic cells and anti-CD154 monoclonal antibody.
AB  - Infusion of donor immature dendritic cells (DC) can significantly prolong
      survival of organ allografts, and this is believed to be due to antigen
      recognition by T cells in the absence of co-stimulation. In this study we report
      that a single pre-operative infusion of donor-mobilized immature plasmacytoid
      dendritic cells (pDCs) is superior to that of other DC sub-sets in suppressing
      allograft rejection. The combination of pDC infusion with injection of anti-CD154
      monoclonal antibody further inhibited graft rejection and, in 50% of the mice,
      led to indefinite graft survival. This finding suggests a role for the
      plasmacytoid DC sub-set in facilitating organ transplant survival and also in the
      treatment of autoimmune disorders.

PMID- 16102451
TI  - Are neointimal smooth muscle cells in human cardiac allograft vasculopathy of
      donor origin?

PMID- 16102452
TI  - Cardiac magnetic resonance perfusion imaging identifies transplant arteriopathy
      by a reduced endomyocardial resting perfusion.

PMID- 16102453
TI  - Lung transplantation: how to do the venous anastomosis when the pulmonary graft
      has no auricular cuff.

PMID- 16102454
TI  - C4d complement component as one of the humoral rejection markers.

PMID- 16102455
TI  - Long-term calcineurin inhibitor "holiday" using daclizumab in a heart transplant
      patient with acute renal dysfunction.

PMID- 16102456
TI  - Recovery from multi-organ failure in a patient with a continuous-flow left
      ventricular assist device.

PMID- 16102457
TI  - A mouse aortic patch model for mechanical circulatory support.

PMID- 16102458
TI  - Antiphospholipid syndrome with anti-prothrombin autoantibodies in a patient with
      an axial-flow left ventricular assist device.
AB  - Autoantibodies to prothrombin, first described almost 50 years ago, are
      paradoxically associated with thrombosis. Described is an unusual case of fatal
      hypercoagulability in a patient with multiple arterial and venous thromboembolic
      complications despite intense anticoagulation while being bridged to
      transplantation with a left ventricular assist device. Serum analysis revealed
      the presence of prothrombin autoantibodies and high titers of anti-nuclear
      antibodies, and autopsy revealed pulmonary arteriolar vasculitis. These findings
      suggest an autoimmune basis for the presence of anti-prothrombin antibodies and
      the hypercoagulable state observed in the present case.

PMID- 16102459
TI  - Successful lung transplantation from a donor with a saddle pulmonary embolus.
AB  - Pulmonary embolus has received scant attention as a contraindication to lung
      donation. Reported is a case of a saddle pulmonary embolus successfully treated
      with thrombolytics in a donor whose lung was ultimately successfully
      transplanted. Discussed are the theoretical likelihood of thromboembolus in
      potential lung donors and the possible implications of pulmonary embolism on
      donor selection and lung physiology around the time of transplantation.

PMID- 16102460
TI  - Elective transplant pneumonectomy in a 38-year-old man.
AB  - Transplant pneumonectomy is a rarely performed procedure. It is occasionally
      carried out in the course of retransplantation. To our knowledge, resection of a
      transplanted lung without its replacement and with successful outcome in the
      adult has not been previously reported. We present a case of elective left
      transplant pneumonectomy in a 38-year-old man 6 years after left single-lung
      transplant. At 12 months after resection, the patient remains well, with good
      exercise tolerance.

PMID- 16102461
TI  - Fatty infiltration of right ventricle (adipositas cordis): an unrecognized cause
      of early graft failure after cardiac transplantation.
AB  - Fatty infiltration of the right ventricle is usually an incidental finding at
      post-mortem, but may have clinical significance at times of physiologic stress.
      We report a case of fatal right ventricular dysfunction immediately after cardiac
      transplantation secondary to massive fatty infiltration of the donor right
      ventricle. Ante-mortem diagnosis of fatty infiltration may be difficult to
      determine despite non-invasive cardiac evaluation. If the diagnosis of fatty
      infiltration is suspected at time of donor harvest, the relative risks and
      benefits of proceeding with transplantation should be carefully assessed.

PMID- 16102462
TI  - Symptomatic acute myocardial infarction in a cardiac transplant recipient
      successfully treated with primary coronary angioplasty: evidence of prognostic
      importance of chest pain after cardiac transplantation.
AB  - Accelerated coronary artery disease remains the limiting factor in the long-term
      survival of heart transplant (HT) recipients and occurs in approximately 50% of
      patients by 5 years after transplantation. Sequelae of graft arteriosclerosis
      include congestive heart failure (due to acute or chronic ischemia), graft loss,
      and death. Unfortunately, as a consequence of cardiac denervation, symptoms are
      often atypical or completely absent, and thus presentation with an acute coronary
      syndrome is extremely uncommon. We describe the case of an HT recipient with a
      typical clinical picture of an acute myocardial infarction (MI), who presented to
      our hospital 2 hours after the onset of symptoms and was successfully treated
      with primary percutaneous transluminal coronary angioplasty (PTCA).

PMID- 16102463
TI  - First clinical implant of the VentrAssist left ventricular assist system as
      destination therapy for end-stage heart failure.
AB  - The VentrAssist device left ventricular assist system, designed for permanent
      implantation, is a novel centrifugal pump with a hydrodynamically suspended
      rotor. The first human implant was into a 72-year-old man with New York Heart
      Association (NYHA) class IV heart failure due to idiopathic dilated
      cardiomyopathy. The implant and recovery were uneventful, and the patient
      survives at 17 months, is NYHA class II, and lives at home. This device shows
      promise in end-stage heart failure for permanent implantation and bridge to
      transplantation.

PMID- 16102464
TI  - Effect of azithromycin on bronchiectasis and pulmonary function in a heart-lung
      transplant patient with severe chronic allograft dysfunction: a case report.
AB  - Azithromycin has been shown to be beneficial in several diseases with chronic
      neutrophilic inflammation of the airways, such as cystic fibrosis and
      bronchiolitis obliterans syndrome (BOS) after lung transplantation. Up to now,
      however, its healing effect on bronchiectasis has never been demonstrated. We
      report a heart-lung transplant patient who developed chronic rejection (BOS stage
      3) with the appearance of gross bronchiectasis on a spiral computed tomography
      (CT) chest scan. Within 2 weeks after starting azithromycin, the patient's forced
      expiratory volume in 1 second increased significantly and a repeat spiral CT
      chest scan 5 months later, showed a major improvement of the bronchiectasis. This
      case report illustrates that bronchiectasis may greatly improve after treatment
      with azithromycin and no longer needs to be considered an endstage finding in
      patients with severe BOS.

PMID- 16102465
TI  - Transplantation of yeast-infected cardiac allografts: a report of 2 cases.
AB  - For the first time in the literature to date, we report 2 cases of
      transplantation of yeast-infected cardiac allografts. In both cases, endocardial
      vegetations were observed before graft implantation. Microbiologic samples grew
      yeasts: Rhodotorula glutinis was found close to the left atrial appendage in the
      first case and Candida parapsilosis was identified in a vegetation located at the
      base of the tricuspid valve in the second case. We discuss the possible routes of
      donor organ infection and management of these 2 unusual cases.

PMID- 16102466
TI  - Lymphocytic myocarditis after lung transplantation.
AB  - This study reports the development of lymphocytic myocarditis in a bilateral lung
      allograft recipient. A 23-year-old woman developed congestive heart failure and
      severe left ventricular dysfunction 32 months after a bilateral lung allograft
      for cystic fibrosis. She had taken oral acyclovir for infectious mononucleosis
      that was diagnosed 11 months previously. Her viral load for Epstein-Barr virus
      (EBV) increased, and an echocardiogram revealed a left ventricular ejection
      fraction of 25% and endomyocardial biopsy revealed lymphocytic myocarditis. She
      received valacyclovir (1 g x 3 times daily) and made a full recovery 6 months
      later.

PMID- 16102467
TI  - Role of B-type natriuretic peptide and effect of nesiritide after total cardiac
      replacement with the AbioCor total artificial heart.
AB  - Endogenous B-type natriuretic peptide (BNP) is thought to be produced in the
      cardiac ventricles. After sub-total cardiectomy and implantation of a total
      artificial heart (TAH), the abrupt withdrawal of BNP impairs renal function
      despite normal hemodynamic variables. We hypothesized that abrupt withdrawal of
      endogenous BNP may impair renal function and volume homeostasis and BNP may have
      a direct renal influence unrelated to its cardiovascular effect. Nesiritide
      infusion should be supplemented in the interim and weaned slowly until BNP levels
      normalize, which suggests that BNP is produced in tissues other than the cardiac
      ventricles.

PMID- 16102468
TI  - For gold, heart rate matters.
AB  - A 19-year-old woman presented with decreased exercise tolerance 3 years after
      orthotopic heart transplantation. Exercise capacity was severely reduced, with a
      maximal workload of 84 W, corresponding to 56% of the predicted value. After
      exclusion of other causes, insufficient heart rate response to exercise was
      considered as the major contributor to her decreased exercise tolerance.
      Correction of this problem with the implantation of an AAIR pacemaker
      dramatically improved her physical performance, allowing her to win 5 gold medals
      at the European Heart and Lung Transplant Games. This case report illustrates how
      pacemaker therapy can dramatically improve the symptoms and performance of
      patients with chronotropic incompetence.

PMID- 16102469
TI  - Bosentan induces clinical, exercise and hemodynamic improvement in a pre
      transplant patient with plastic bronchitis after Fontan operation.
AB  - We present a 14-year-old pre-transplant boy with elevated pulmonary pressure and
      plastic bronchitis after Fontan operation despite stent fenestration, who
      improved with long-term oral administration of the endothelin antagonist,
      bosentan. Bosentan improved the patient's symptoms and aortic saturation, World
      Health Organization class, maximal and sub-maximal exercise capacity, Borg
      dyspnea index, invasively measured mean pulmonary pressure, pulmonary blood flow
      and pulmonary vascular resistance. This is the first literature report examining
      the effect of endothelin antagonism in failing Fontan circulation and showing
      clinical, exercise and hemodynamic improvement with bosentan in a pre-transplant
      Fontan patient with high pulmonary pressure and plastic bronchitis.

PMID- 16102471
TI  - Building a successful support group for post-amputation patients.
AB  - The purpose of this article is to identify five steps to attain a successful
      amputee support group and share the process for establishing and maintaining a
      peer visitation program for in-patient amputees. Whatever the cause, losing a
      limb is a life-changing event that one should not go through alone. Support
      groups can assist patients and their families through this transition in a
      positive and healthy way.

PMID- 16102472
TI  - The importance of obtaining ankle-brachial indexes in older adults: the other
      vital sign.
AB  - As the aging population increases, so does the need to identify specific health
      problems associated with that age group and to develop and implement strategies
      to manage those problems efficiently. Peripheral arterial disease, a known threat
      to older adults' health and independence, often leads to decreased functional
      ability and potential limb loss. Nurses are in a unique position to screen older
      adults for the disease and to implement strategies to manage the problem. An
      overview of arterial physiology will be presented along with identification of
      risk factors, how to obtain ankle-brachial indexes and interpret the results, and
      treatment options for mild, moderate, and severe disease. Identifying the disease
      in its early stages and minimizing the effects will help keep older adults living
      independently and improve their quality of life.

PMID- 16102473
TI  - Implementing evidence-based practice: walking the talk.
AB  - Russworm and Larrabee's (1999) six-step model for evidence-based practice (EBP)
      was used by 10 nursing teams to seek answers to clinical questions. These teams,
      primarily composed of staff nurses, participated in a health region-wide EBP
      program over 1 year. Overall, the model served as a useful mechanism for
      examining practice-derived questions. However, additional strategies needed to be
      incorporated by the project teams. These included making decisions about
      change/no change at an earlier stage than was suggested by the model; seeking
      additional evidence including survey data to benchmark "best" practices; and
      ensuring colleagues' and managers' input, support, and involvement. Four project
      teams (three of which addressed nursing procedural questions) found insufficient
      empirical evidence on which to base change; the outlook for directing evidence
      based practice was promising for the remaining six projects. The EBP program was
      judged to be highly satisfactory to participants and their managers.

PMID- 16102474
TI  - The impact of type 2 diabetes and peripheral arterial disease on quality of life.
AB  - Peripheral arterial disease (PAD) is associated with impaired walking distance as
      the result of claudication and reduced quality of life (QOL). Diabetes mellitus
      (DM) is commonly associated with PAD. The combined effect of DM and PAD versus
      PAD alone on walking distance and QOL is not well understood. This prospective,
      descriptive study examined walking distance and QOL associated with DM and PAD
      compared with PAD alone. Walking distance was assessed by an exercise treadmill
      test to determine initial claudication distance and absolute claudication
      distance and by self-report using the Walking Impairment Questionnaire. QOL was
      measured using the Short Form-36. The overall sample consisted of 92 men and
      women with PAD and DM or PAD alone. Of the total sample, 74 participants had PAD
      with ABI less than 0.9 mm Hg and 18 subjects had PAD and uncontrolled DM with
      hemoglobin A1c 7.0 mg/dL or greater. The mean age was 72 years (standard
      deviation [SD] = 7) for the PAD only group and 75 years (SD = 8) (not
      significant) for the PAD and DM groups. Initial claudication distance was greater
      in subjects with PAD only (186.9 m, SD = 136.4) than in diabetic subjects with
      PAD (127.3 m, SD = 70.0, P = .01). Absolute claudication distance was higher in
      patients with PAD only (461.3 m, SD 308) than in diabetic subjects with PAD
      (279.1 m, SD = 100, P = .01). Self-reported walking speed was reduced in patients
      with DM and PAD compared with patients with PAD only (P = .05). Diabetic patients
      with PAD reported impaired role function (P = .007), general health (P = .03),
      and social function (P = .04) compared with patients with PAD only. We conclude
      that DM has a significant detrimental impact on walking distance and QOL in
      patients with PAD. These findings suggest that diabetic patients with PAD are at
      greater risk for experiencing social isolation, impaired role function, reduced
      overall perceptions of general health, and impaired functional capacity. Future
      studies with larger sample sizes are needed to identify factors that contribute
      to these perceptions in diabetic patients with PAD.

PMID- 16102475
TI  - Teaching the Ankle-Brachial Index in nursing: a new core competency.

PMID- 16102476
TI  - Lipid management in patients with vascular disease.
AB  - Cardiovascular disease is the leading cause of disability and death in the United
      States. Although the role of lipids in the atherosclerotic process is well
      established, the management of dyslipidemia is often suboptimal. The National
      Cholesterol Education Program and its Adult Treatment Panel III have established
      treatment guidelines for dyslipidemia. This article will define the problem of
      dyslipidemia in vascular patients and discuss the recommendations of the National
      Cholesterol Education Program and Adult Treatment Panel III and the implications
      for health care personnel.

PMID- 16102477
TI  - Pediatric ophthalmology and strabismus in Mexico.

PMID- 16102478
TI  - Selected pigmented fundus lesions of children.
AB  - BACKGROUND: Ocular cells that accumulate melanin pigment are derived from 1 of 2
      sources, the optic vesicle or the neural crest. Migration and distribution of
      pigment containing cells may go awry during fetal development or these cells may
      be altered before or after birth either by local or systemic stimuli. Specific
      recognition patterns of pigment distribution often exist and may relate directly
      to a single disease process. METHODS: Records of pediatric patients with
      disorders of pigment distribution in the ocular fundi who had been examined by
      the author were reviewed. RESULTS: Five disorders with recognizable patterns of
      retinal pigment epithelium (optic vesicle derivation) disturbance (congenital
      hypertrophy of the retinal pigment epithelium, Gardner syndrome, chronic
      granulomatous disease, preserved para-arteriole retinal pigment epithelium in
      (autosomal-recessive) retinitis pigmentosa, and combined hamartoma of the retina
      and retinal pigment epithelium), and 5 disorders of cells originating from the
      neural crest (choroidal nevi, choroidal melanoma, melanocytoma, ocular melanosis,
      and oculodermal melanosis), were selected for illustration and discussion.
      CONCLUSIONS: These arbitrarily selected groups of disorders affect or involve
      patterns of pigment deposition in the ocular fundus. These patterns are
      recognizable and distinguishable one from another but have different implications
      for treatment and follow-up. Progress in recognizing distinguishing
      characteristics, diagnostic implications, understanding, and treatment of these
      disorders during the past 40 years is compared and contrasted between the 2
      groups.

PMID- 16102479
TI  - Sutureless ophthalmic surgery: a scaffold-enhanced bioadhesive technique.
AB  - PURPOSE: Bioadhesives have had limited use in ophthalmic surgery. Problems with
      these adhesives have included inadequate tensile strength and difficulty with
      their application to the tissue site. We evaluated a scaffold-enhanced
      cyanoacrylate bioadhesive composite as an alternative to sutures in ophthalmic
      surgery, including strabismus procedures. METHODS AND MATERIALS: The bioadhesive
      composite consisted of 2-octyl-cyanoacrylate combined with either a poly(L-lactic
      co-glycolic acid) (PLGA) scaffold or a rehydrated porcine small intestine
      submucosa (SIS) scaffold. Extraocular rectus muscle and sclera were obtained from
      rabbits (n = 40) and were used, with these bioadhesive composites, to produce
      rectus muscle-to-sclera, sclera-to-sclera, and rectus muscle-to-rectus muscle
      adhesions. Control adhesions were created with cyanoacrylate only. The breaking
      load of the tissue repair was measured with a material strength-testing machine.
      RESULTS: In all cases, the scaffold-enhanced cyanoacrylate adhesions were
      significantly stronger (P < 0.001) than the cyanoacrylate alone. The rectus
      muscle-to-sclera adhesions were greater than the in vivo forces reported for the
      horizontal rectus muscles in humans in extreme gaze. CONCLUSION: This scaffold
      enhanced bioadhesive composite produced initial muscle-sclera adhesions with
      strength satisfactory for strabismus surgery. It also may be applicable to other
      categories of ophthalmic surgery as a substitute for sutures.

PMID- 16102480
TI  - Is the tono-pen accurate for measuring intraocular pressure in young children
      with congenital glaucoma?
AB  - PURPOSE: We sought to compare intraocular pressure (IOP) measurements by Perkins
      tonometer and Tono-Pen in young children with primary congenital glaucoma (PCG).
      METHODS: This was a retrospective comparative case series. We reviewed the
      clinical records of all children with primary congenital glaucoma who underwent
      examinations under general anesthesia at Soroka University Medical Center between
      January 1999 and July 2002. Our main outcome measures were IOP with Perkins hand
      held tonometer and Tono-Pen tonometer. RESULTS: A total of 28 eyes of 16 children
      were examined under general anesthesia. The mean IOP was 18 +/- 6 mm Hg with the
      Perkins tonometer and 22 +/- 8 mm Hg with the Tono-Pen. In 18 eyes, IOP was less
      than 21 mm Hg with the Perkins tonometer; these eyes had already undergone
      surgical procedures. The other 10 eyes with IOP greater than 21 mm Hg with the
      Perkins tonometer underwent surgery at the end of the examination under
      anesthesia. In eyes with IOP greater than 16 mm Hg (Group A, n = 18), a
      significant difference (P < 0.001) was found between the Perkins and Tono-Pen
      measurements, even although the values were strongly correlated (r = 0.60). In
      contrast, in eyes with IOP less than 16 mm Hg (Group B, n = 10) no statistically
      significant difference (P = 0.28) and good correlation (r = 0.78) were obtained.
      A difference of 5.8 +/- 3.8 mm Hg and 0.6 +/- 1.7 mm Hg between Perkins and Tono
      Pen readings, respectively, was found in Groups A and B. CONCLUSIONS: Tono-Pen
      readings disagree with Perkins tonometer measurements for measuring IOP in
      children with PCG who present with IOP greater than 16 mm Hg and tends to
      overestimate IOP. A further study with a similar population is necessary to
      confirm these results.

PMID- 16102481
TI  - Central corneal thickness and glaucoma in aphakic and pseudophakic children.
AB  - BACKGROUND: The risk of glaucoma among aphakic children is as high as 32%, based
      primarily on intraocular pressure (IOP) measurements. Although IOP may be falsely
      elevated by increased central corneal thickness, central corneal thickness (CCT)
      values have not been reported in this population. METHODS: Patients from the
      practices of 2 pediatric ophthalmologists and 2 glaucoma specialists had
      measurements of CCT, IOP, and optic nerve cupping, with visual field analysis
      when possible. Normal fellow eyes of unilateral aphakes and pseudophakes were
      included as controls. RESULTS: In 36 aphakic and 6 pseudophakic eyes CCT averaged
      660 microns compared with 576 microns for phakic fellow eyes (P < 0.0001).
      Glaucoma, defined by IOP at least 35 mm Hg or by IOP at least 22 mm Hg associated
      with optic nerve changes, occurred in 21% of 28 aphakic patients but in no
      pseudophakic patient. CONCLUSIONS: CCT in aphakic/pseudophakic children is
      substantially increased compared with control patients. These values may be
      important in interpreting IOP measurements in these children.

PMID- 16102482
TI  - Combined intraocular lens implantation and glaucoma implant (tube shunt) surgery
      in pediatric patients: a case series.
AB  - PURPOSE: We sought to investigate the outcomes of children who underwent
      simultaneous intraocular lens (IOL) implant and glaucoma implant surgery.
      METHODS: Medical records of all patients who underwent simultaneous IOL implant
      and glaucoma implant surgery from January 1995 through August 2003 by a single
      surgeon were reviewed. Criteria for success included intraocular pressure </=22
      mm Hg, or judged adequate for glaucoma severity, without vision loss or
      devastating complication. RESULTS: The study included 9 eyes of 8 children who
      had a mean age of 7.6 years (range, 1-16) and a mean follow-up time of 21 months
      (range, 8.5-35 months) after simultaneous IOL (either cataract removal with
      primary IOL, 2 eyes; or secondary IOL implantation, 7 eyes), and glaucoma implant
      surgery (6 Baerveldt, 3 Ahmed). The indications for combined surgery fell into 3
      basic categories: unilateral aphakia with glaucoma (4/9), anatomical features
      (such as shallow anterior chamber and/or vitreous in the pupillary plane) making
      an IOL helpful in positioning the tube away from corneal endothelium and/or
      vitreous (4/9), and unilateral traumatic cataract (1/9). Mean intraocular
      pressure for operated eyes was 29 mm Hg (range, 21-44) preoperatively and fell to
      17 mm Hg (range, 11-22) at last follow up, P = 0.01. The mean number of glaucoma
      medications was 3.5 preoperatively (range, 2-5) versus 1.9 (range, 0-4) at last
      follow-up (p = NS). Complications (n = 5) were varied, only 2 of which required
      additional surgery. Eighty-nine percent (8/9) of patients met criteria for
      success at last follow-up. CONCLUSIONS: Selected children can do well after
      combined glaucoma implant and IOL surgery, achieving both satisfactory glaucoma
      control and stable visual acuity.

PMID- 16102483
TI  - Ahmed valve implantation for uncontrolled pediatric uveitic glaucoma.
AB  - PURPOSE: We sought to evaluate the safety and efficacy of Ahmed valve
      implantation for the management of glaucoma associated with chronic uveitis in
      pediatric patients. METHODS: A retrospective chart review was conducted of 6
      pediatric patients (7 eyes) who underwent Ahmed valve implantation because of
      refractory uveitic glaucoma. Intraocular pressure (IOP) reduction, preoperative
      and postoperative visual acuities, the number of hypotensive medications
      required, and complications associated with the operation were evaluated.
      RESULTS: Mean follow-up was 36.8 months (range, 6-60). At the last visit, all 7
      eyes had IOPs between 9 and 18 mm Hg (average, 12.1). IOP reduction averaged
      69.6% (P = 0.0005, paired t-test). The number of hypotensive agents was reduced
      from an average of 3 to an average of 0.71 medicines per eye (P = 0.001). The
      only complication was hemorrhagic choroidal detachment postoperatively in two
      eyes; both resolved within one month. CONCLUSIONS: For children with good
      immunomodulatory control of their inflammation and appropriate follow-up, Ahmed
      valve implantation can be an effective and safe procedure for treating pediatric
      uveitic glaucoma.

PMID- 16102484
TI  - Treatment of inferior oblique paresis with superior oblique silicone tendon
      expander.
AB  - INTRODUCTION: Patients with inferior oblique eye muscle paresis may show
      hypotropia and apparent superior oblique muscle overaction on the side of the
      presumed weak inferior oblique (IO) muscle. We report 8 such patients
      successfully treated using unilateral silicone superior oblique (SO) tendon
      expanders. METHODS: Eight consecutive cases over the course of 6 years from the
      authors' private practice are described. None had a history of head trauma or a
      significant neurologic event. All patients showed IO paresis by 3-step test, with
      incyclotorsion and SO overacton of the hypotropic (paretic) eye. Forced ductions
      of the hypotropic eye were normal in all cases, and the vertical strabismus was
      treated with placement of a 7- mm silicone SO tendon expander in the hypotropic
      (paretic) eye. RESULTS: Mean preoperative primary position hypotropia was 6.5
      prism diopters (PD); mean postoperative was 0.5 PD. Seven of 8 patients had
      resolution of primary position hypotropia, whereas the eighth was reduced. Mean
      preoperative SO overaction was 3+; all patients had postoperative resolution of
      SO overaction. Of 4 patients with preoperative ocular torticollis, mean
      preoperative head tilt was 9.3 degrees; mean postoperative tilt was 2.9 degrees.
      Two patients' head tilts had resolved, the other 2 showed improvement. All
      patients showed preoperative incylclotorsion of the hypotropic (paretic) eye;
      inclyclotorsion resolved in all patients after the placement of a SO tendon
      expander. CONCLUSION: The silicone SO tendon expander effectively restores ocular
      alignment in IO paresis with apparent SO overaction. Associated ocular
      torticollis can also be improved.

PMID- 16102485
TI  - Secondary intraocular lens implantation for pediatric aphakia.
AB  - PURPOSE: We sought to report the outcome of secondary intraocular lens (IOL)
      implantation in children. METHODS: This was a retrospective case review. RESULTS:
      A total of 77 eyes were identified. An average age at secondary implantation was
      7.8 +/- 5.0 years, whereas the average age at primary cataract surgery was 1.5 +/
      2.6 years. Average follow-up was 2.7 +/- 1.9 years. Thirty eyes received a
      hydrophobic acrylic IOL implantation whereas 47 eyes received a PMMA IOL. The
      sites of fixation for implanted IOLs were as follows: anterior-chamber (n = 6),
      sulcus (n = 42), in-the-bag (n = 14), optic-capture (n = 6), piggyback (n = 4),
      and sutured (n = 5). Complications included clinically significant decentration,
      4 (5.2%); visual axis opacification, 4 (5.2%); dislocation of the IOL, 2 (2.6%);
      and pupillary capture requiring repositioning of IOL, 1 (1.3%). Clinically
      significant decentration requiring surgical intervention was noted only in eyes
      with sulcus-fixated foldable IOLs (28.6%; 4/14). None of the 29 eyes with sulcus
      fixated PMMA IOL implantation developed decentration. All the decentrations were
      in an inferior direction and occurred in eyes of male patients (P = 0.03). Eyes
      with an axial length of >23 mm were 4 times more likely to develop decentration
      if implanted with a sulcus-fixated foldable IOL when compared with eyes measuring
      <23 mm (P = 0.03). Postoperative geometric mean visual acuity was significantly
      better than preoperative visual acuity (P < 0.001). CONCLUSION: Secondary IOL
      implantation can be safely achieved in pediatric eyes. In-the-bag fixation of
      foldable IOLs is associated with a low rate of complications. Foldable lenses
      appear to have a higher rate of decentration than PMMA lenses when placed in the
      sulcus in eyes of myopic male patients.

PMID- 16102486
TI  - Functional and structural outcomes following lensectomy for ectopia lentis.
AB  - PURPOSE: High refractive errors and optical aberrations reduce vision when the
      lens edge bisects the pupil. We studied outcomes of eyes with ectopia lentis
      following lensectomy. METHODS: Charts of 11 consecutive patients with bilateral
      ectopia lentis who underwent lensectomy-anterior vitrectomy in at least one eye
      from 1985 to 2004 were reviewed. Eighteen eyes were operated. One eye was
      excluded due to short-term follow-up (<2 years). RESULTS: Mean age at surgery was
      7.7 years (2 to 17 years). Median follow-up after lensectomy was 10 years (range
      2 to 16 years). Six eyes were followed for 6 to 10 years, and another six eyes
      were followed for 11 to 16 years. Patient diagnoses included Marfan syndrome
      (nine eyes), ectopia lentis et pupillae (three eyes), simple ectopia lentis (two
      eyes), homocystinuria (two eyes), and sporadic spherophakia (one eye).
      Preoperative best-corrected visual acuity (BCVA) ranged from 20/60 to light
      perception, and postoperative BCVA ranged from 20/20 to 20/100 (14 eyes were at
      least 20/30). Complications included posterior vitreous detachment (two eyes,
      12%), glaucoma (one eye, 6%), transient ocular hypertension (one eye, 6%), wound
      dehiscence with iris incarceration (one eye, 6%), transient vitreous hemorrhage
      (one eye, 6%), and peripheral anterior synechiae (one eye, 6%). No retina
      detached. CONCLUSIONS: Our cohort of patients with long-term follow-up shows that
      pars plana lensectomy can be successful in restoring vision when conservative
      measures fail.

PMID- 16102487
TI  - Interocular axial length difference in eyes with pediatric cataracts.
AB  - PURPOSE: We sought to report interocular axial length difference (IALD) between
      the operated eye and fellow eye at the time of pediatric cataract surgery.
      METHODS: A retrospective analysis of 171 cataractous (operated) eyes (mean
      patient age at surgery, 56.9 months; range, 0.2-230.0) was undertaken.
      Descriptive statistics, analysis of covariance, and regression analysis were used
      in statistical analysis. RESULTS: The mean IALD was 0.05 +/- 1.15 mm. If absolute
      values were used, mean IALD was 0.76 +/- 0.86. Nearly half of the subjects
      (48.0%) showed an IALD of >/=0.5 mm. Forty-one patients (24.0%) had operated
      (cataractous) eyes that were >/=0.5 mm shorter than the fellow eye, and 41
      patients (24.0%) had operated eyes that were >/=0.5 mm longer than the fellow
      eye. The mean IALD in unilateral and bilateral cases was 0.10 +/- 1.33 and -0.03
      +/- 0.76, respectively (P = 0.4). If absolute values were used, it was 0.98 +/-
      0.90 and 0.40 +/- 0.65 in unilateral and bilateral cases, respectively (P <
      0.001). IALD was more predictable in unilateral than in bilateral cases (P <
      0.001). In unilateral cases, age at surgery (P = 0.04) and AL of the operated eye
      (P < 0.001) correlated with IALD. IALD did not correlate with gender, ethnicity,
      or type of cataract in either unilateral or bilateral cases. CONCLUSIONS: An IALD
      of >/=0.5 mm occurred in 48.0% of patients with pediatric cataracts and occurred
      more often with unilateral cataractous patients than with bilateral cases. In
      patients with unilateral cataract, age at surgery and AL of the operated eye
      could help predict the IALD.

PMID- 16102488
TI  - Comparison of clinical findings in pediatric patients with albinism and different
      amplitudes of nystagmus.
AB  - INTRODUCTION: Visual acuity in albinism can vary and is difficult to predict. We
      undertook this study to investigate whether patients with albinism with absent or
      minimal nystagmus have better visual acuity and ocular alignment than patients
      with albinism and obvious nystagmus. METHODS: Our retrospective chart review of
      38 pediatric patients with albinism yielded 16 patients with absent or minimal
      nystagmus and 22 patients with obvious nystagmus. RESULTS: Patients with albinism
      and absent or minimal nystagmus had best-corrected visual acuities ranging from
      20/20 to 20/50, with a mean visual acuity of 20/33. Those patients with albinism
      and obvious nystagmus had best-corrected visual acuities ranging from 20/30 to
      20/200, with a mean visual acuity of 20/80. Visual acuity was significantly
      better in the group with absent or minimal nystagmus (P < 0.001). Of the 16
      patients with absent or minimal nystagmus, 6 were orthophoric and 10 had a
      strabismic deviation of 12 prism diopters (PD) or less. None of these patients
      required strabismus surgery. Of the 22 patients with nystagmus, 16 were
      orthophoric, 1 had a horizontal deviation of less than 12 PD, and 5 had larger
      angle horizontal deviations ranging from 20 to 50 PD. CONCLUSION: Our findings
      suggest that pediatric albinism patients with absent or minimal nystagmus can be
      expected to demonstrate better visual acuity and are less likely to show a
      strabismic deviation of greater than 12 PD compared with those with obvious
      nystagmus (P = 0.0003).

PMID- 16102489
TI  - Eye movement abnormalities in hermansky-pudlak syndrome.
AB  - BACKGROUND: Hermansky-Pudlak Syndrome (HPS) is a type of oculocutaneous albinism
      associated with a bleeding diathesis and pulmonary fibrosis. Although it is known
      that patients with HPS exhibit nystagmus, the nature of these abnormal eye
      movements has not been studied. METHODS: Twenty-seven patients with HPS,
      diagnosed by platelet morphology and genetic analysis, underwent a systemic
      evaluation and complete eye examination. Twenty-five had eye movement recordings
      using magnetic search coil, infrared, or video oculography. RESULTS: All patients
      had iris transillumination, foveal hypoplasia, and variable hypopigmentation in
      skin and eyes. All had bleeding tendencies, and 2 reported excessive bleeding
      during strabismus surgery. Nine patients had pulmonary fibrosis. Visual acuities
      ranged from 20/20- to 20/320. Twenty patients had strabismus despite 6 having
      strabismus surgery previously. Ocular oscillations consistent with congenital
      nystagmus (CN) were clinically evident in 24 of 27 patients, and half showed
      periodic alternating nystagmus. In 3 patients without CN, eye movement recordings
      revealed minimal end-gaze nystagmus, square-wave jerks, drift during fixation and
      saccades, and low-gain pursuit. These patients had melanin in the posterior pole
      and better visual acuities than the others (P = 0.002). CONCLUSIONS: Most
      patients with HPS have CN, and many have periodic alternating nystagmus. Some
      have subtle eye movement abnormalities without clinically evident nystagmus,
      which can obscure the diagnosis, especially if hypopigmentation is mild. Absence
      of clinical nystagmus in a child with HPS suggests good vision. Patients with
      albinism, especially before surgery, should be evaluated for HPS to prevent life
      threatening complications.

PMID- 16102490
TI  - Clinical course and outcome of uveitis in children.
AB  - PURPOSE: We sought to evaluate the clinical course, complications, and visual
      outcome of pediatric uveitis. METHODS: Our sample included 38 consecutive
      children with uveitis treated between 1986 and 2002: 15 with idiopathic uveitis,
      10 with Behcet disease, 9 with juvenile rheumatoid arthritis, 4 with other
      diagnoses. The last group was excluded from the analysis because of its small
      size. Appropriate ophthalmologic and laboratory examinations were obtained.
      Treatment consisted of topical, periocular, or systemic steroids with or without
      immunosuppression. RESULTS: Complications occurred in all 3 groups, although they
      tended to be more severe in the patients with juvenile rheumatoid arthritis.
      Visual acuity improved from presentation to final examination; the difference was
      statistically significant for the patients with idiopathic uveitis (P < 0.0005)
      and Behcet disease (P = 0.004). CONCLUSIONS: These findings support an intensive
      treatment approach to childhood uveitis. The visual prognosis is good even in
      patients with a severe clinical course.

PMID- 16102491
TI  - The effect of initial recognition of abnormalities by physicians on outcome of
      retinoblastoma.
AB  - PURPOSE: The purpose of this study was to assess the effect of early diagnosis by
      physicians on outcome of retinoblastoma. METHODS: This was an observational case
      series in which the records of 36 patients with retinoblastoma were reviewed. The
      age at onset of first symptoms and diagnosis, identity of the individual who
      first recognized an abnormality, treatment, and outcome were analyzed. RESULTS:
      Twenty-two patients had unilateral retinoblastoma. Both eyes were preserved in
      only 2 of these patients, both of whom had abnormalities first noted by their
      pediatricians. Fourteen patients had bilateral retinoblastoma. Both eyes were
      preserved in the 5 bilateral patients who were monitored from birth with serial
      examinations under anesthesia because of family histories of retinoblastoma.
      Enucleation of at least 1 eye was required in 8 of the 9 bilateral patients whose
      families first noted abnormalities. Enucleation of at least 1 eye was required in
      27 of 28 patients (96%) in whom abnormalities were first noted by parents.
      CONCLUSION: In this series, the only patients with unilateral retinoblastoma who
      did not require enucleation were those in whom pediatricians, rather than family
      members, first noted ocular abnormalities. Both eyes were preserved in all
      patients with bilateral retinoblastoma who underwent serial examinations under
      anesthesia because of family histories of retinoblastoma. The prognosis for
      retinoblastoma appears to be greatly improved when physicians initially detect
      abnormalities. Educational efforts directed at early detection of retinoblastoma
      by pediatricians and other primary care providers should be encouraged.

PMID- 16102492
TI  - Releasable adjustable suture technique for children.
AB  - PURPOSE: Residual esotropia is a problem for children with esotropia that can
      follow bilateral medial rectus recession, and the use of adjustable sutures is
      nearly impossible. The aim of this work is to describe a new suture technique to
      overcome this problem. METHODS: Medial rectus muscle was recessed and secured to
      the sclera at the predetermined recession position after suspending it 1.50-2.00
      mm farther. A second, releasable suture was placed at the original insertion
      site, passed under the previously tied muscle suture knot, and tied in a
      strengthened loop knot, advancing the muscle to the new scleral insertion. The
      looped end was left long enough to be kept in the inferior fornix. The next day,
      if the child was undercorrected, intranasal midazolam was given and the
      releasable suture was drawn out, providing additional muscle recession. Patients
      aged 10 to 94 months (mean 34 months) with angle of deviation 20 to 60 prism
      diopters (PD; mean 33 PD) and with follow-up 1 to 12 weeks (mean 4.5 weeks) were
      studied. Success was defined as alignment within 10 PD. RESULTS: Of 50 children
      with esotropia, 32 (64%) were successfully aligned, and 18 (36%) were
      undercorrected with residual angle 14 to 25 PD (mean, 18 PD). After release of
      the suture, 15 children (83%) were successfully aligned, and 3 children were
      still undercorrected. The overall success rate was 94%. CONCLUSION: Releasable
      adjustable suture is a new technique that can help strabismologists attempt
      bilateral medial rectus recession in children, with a second chance for
      correction during early postoperative period.

PMID- 16102493
TI  - Congenital hyperplastic persistent pupillary membranes: a conservative approach
      in management.

PMID- 16102494
TI  - Vertical upper-lid split incision for access to a severely restricted superior
      rectus muscle in a patient with graves ophthalmopathy.

PMID- 16102495
TI  - False passage: a complication of 360 degrees suture trabeculotomy.

PMID- 16102496
TI  - Congenital Brown's syndrome treated with exaggerated traction testing alone.

PMID- 16102497
TI  - Proceedings of the 4th International Workshop on Computer Simulation and
      Experimental Assessment of Cardiac Electrical Function, June 14-15, 2004, Cap
      d'Ail, France.

PMID- 16102498
TI  - Cardiac repolarization. The long and short of it.
AB  - Heterogeneity of transmural ventricular repolarization in the heart has been
      linked to a variety of arrhythmic manifestations. Electrical heterogeneity in
      ventricular myocardium is due to ionic distinctions among the three principal
      cell types: Endocardial, M and Epicardial cells. A reduction in net repolarizing
      current generally leads to a preferential prolongation of the M cell action
      potential. An increase in net repolarizing current can lead to a preferential
      abbreviation of the action potential of right ventricular epicardium or left
      ventricular endocardium. These changes can result in amplification of transmural
      heterogeneities of repolarization and thus predispose to the development of
      potentially lethal reentrant arrhythmias. The long QT, short QT, Brugada and
      catecholaminergic VT syndromes are all examples of pathologies that have very
      different phenotypes and aetiologies, but share a common final pathway in causing
      sudden death via amplification transmural or other spatial dispersion of
      repolarization within the ventricular myocardium. These same mechanisms are
      likely to be responsible for life-threatening arrhythmias in a variety of other
      cardiomyopathies ranging from heart failure and hypertrophy, which may involve
      mechanisms very similar to those operative in long QT syndrome, to ischaemia and
      infarction, which may involve mechanisms more closely resembling those
      responsible for the Brugada syndrome.

PMID- 16102499
TI  - Of circles and spirals: bridging the gap between the leading circle and spiral
      wave concepts of cardiac reentry.
AB  - The "leading circle model" was the first detailed attempt at understanding the
      mechanisms of functional reentry, and remains a widely-used notion in cardiac
      electrophysiology. The "spiral wave" concept was developed more recently as a
      result of modern theoretical analysis and is the basis for consideration of
      reentry mechanisms in present biophysical theory. The goal of this paper is to
      present these models in a way that is comprehensible to both the biophysical and
      electrophysiology communities, with the idea of helping clinical and experimental
      electrophysiologists to understand better the spiral wave concept and of helping
      biophysicists to understand why the leading circle concept is so attractive and
      widely used by electrophysiologists. To this end, the main properties of the
      leading circle and spiral wave models of reentry are presented. Their basic
      assumptions and determinants are discussed and the predictions of the two
      concepts with respect to pharmacological responses of arrhythmias are reviewed. A
      major difference between them lies in the predicted responses to Na(+)-channel
      blockade, for which the spiral wave paradigm appears more closely to correspond
      to the results of clinical and experimental observations. The basis of this
      difference is explored in the context of the fundamental properties of the
      models.

PMID- 16102500
TI  - Genesis of the P wave: atrial signals as generated by the equivalent double layer
      source model.
AB  - AIM: To assess the effectiveness of the equivalent surface source model in the
      simulation of atrial signals as observed in ECG leads. METHODS: P waves were
      extracted from 64-lead ECGs recorded in healthy subjects. The geometries of
      torso, lungs, heart, and blood cavities of a healthy subject, derived from
      magnetic resonance imaging, were used to position a detailed, thick-walled 3D
      model of the atria consisting of a set of 800,000 units representing the activity
      of all atrial myocytes. The ion-kinetics of the units was based on the
      formulation of Courtemanche et al. The simulated transmembrane potentials
      following a normal sinus beat, as well as those during atrial fibrillation, were
      projected on the 1297 nodes of the surface encapsulating all atrial myocytes
      (endocardium and epicardium). The transmembrane potentials at these nodes formed
      the source strengths of the elements of the equivalent generator, which were used
      to compute body surface potentials. RESULTS: After invoking slight adaptations of
      the timing of depolarization of the transmembrane potentials, the simulated
      signals during the P wave closely corresponded to recorded ones. The
      correspondence during the entire PR interval improved markedly after the
      inclusion of early repolarization effects in the interval between the end of the
      P wave and onset of QRS. This demanded a shortening of the mean action potential
      duration generated by the Courtemanche model. The simulated ECGs related to
      atrial fibrillation demonstrated the characteristic features of those clinically
      observed. CONCLUSIONS: The equivalent double layer is a useful source model for
      the genesis of atrial signals observed on the thorax. The interval from the end
      of the P wave to onset of QRS is not iso-electric. The Courtemanche model of the
      ion-kinetics of atrial cells needs to be adapted when applied to represent the
      activity of healthy, 'common' atrial myocytes.

PMID- 16102501
TI  - Volume conductor effects involved in the genesis of the P wave.
AB  - AIM: To assess the effect of inhomogeneities in the conductivity of different
      tissues, such as blood and lung tissue, on the body surface potentials generated
      by atrial electrical activity. METHODS: A 64-lead ECG from a healthy subject was
      recorded. The subject's geometries of torso, lungs, heart, and blood cavities
      were derived by magnetic resonance imaging. These geometries were used to
      construct a numerical volume conductor model. The boundary element method was
      applied to simulate the potentials on the surface of the thorax generated by the
      atria. The equivalent double layer served as the source description during
      depolarization. Recorded body surface potentials were used as a check on the
      simulations. Subsequently, the conductivities in the model were varied to
      determine their influence on P wave morphology and amplitude. RESULTS: The model
      with realistic conductivity values for blood and lungs produced potentials that
      closely matched the measured ones (correlation 98%). The subsequent variation of
      conductivity of blood and lungs revealed a major influence on P wave morphology
      and amplitude: a mean reduction in amplitude by 42%, with pronounced inter-lead
      differences. CONCLUSION: The inhomogeneities of lungs and atrial blood cavities
      need to be incorporated in volume conductor models linking atrial electric
      activity to body surface potentials.

PMID- 16102502
TI  - Can orthogonal lead indicators of propensity to atrial fibrillation be accurately
      assessed from the 12-lead ECG?
AB  - AIMS: When analyzing P-wave morphology, the vectorcardiogram (VCG) has been shown
      useful to identify indicators of propensity to atrial fibrillation (AF). Since
      VCG is rarely used in the clinical routine, we wanted to investigate if these
      indicators could be accurately determined in VCG derived from standard 12-lead
      ECG (dVCG). METHODS: ECG and VCG recordings from 21 healthy subjects and 20
      patients with a history of AF were studied. dVCG was calculated from ECG using
      the inverse Dower transform. Following signal averaging of P-waves, comparisons
      were made between VCG and dVCG, where three parameters characterizing signal
      shape and 15 parameters describing the P-wave morphology were used to assess the
      compatibility of the two recording techniques. The latter parameters were also
      used to compare the healthy and the AF groups. RESULTS: After transformation, P
      wave shape was convincingly preserved. P-wave morphology parameters were
      consistent within the respective groups when comparing VCG and dVCG, with better
      preservation observed in the healthy group. CONCLUSION: VCG derived from routine
      12-lead ECG may be a useful alternate method for studying orthogonal P-wave
      morphology.

PMID- 16102503
TI  - Anatomy of the inferior interatrial route in humans.
AB  - AIMS: To explore the morphology of the proximal coronary sinus (CS) and the
      surrounding tissues in order to identify possible routes for interatrial
      conduction. METHOD: Specimens containing interatrial septum and proximal CS were
      taken from 21 necropsied hearts and sliced into 10-microm thick parallel
      histological sections in 1-mm steps starting from the valve plane, up to the
      atrial roof (40-80 sections per heart). The sections were stained with van
      Gieson's stain. RESULTS: Media in the proximal CS consists of smooth muscle cells
      that do not form a continuous layer. CS was not surrounded by striated atrial
      myocardium in 10 specimens in which posterior CS wall was covered by epicardial
      fat only. In seven specimens, striated muscle bundles of up to 2-mm width
      connected the myocardium surrounding the CS with the left atrium. Regardless of
      their presence, variable posterior and/or anterior interatrial muscular
      connections were identified in all specimens. CONCLUSION: Variability of the
      striated atrial myocardium surrounding proximal CS may affect interatrial
      conduction. Striated muscular fascicles connecting the proximal CS with the left
      atrium are not obligatory cardiac structures and may be considered as
      supplementary to the larger interatrial connections outside the CS.

PMID- 16102504
TI  - An integrative model of mouse cardiac electrophysiology from cell to torso.
AB  - AIMS: Although the transgenic mouse has become an important new tool in the study
      of human diseases and the design of new therapies, a complete picture of cardiac
      electrophysiology in the mouse, from genome to body surface, is lacking. A
      computational model of the mouse heart is presented, which is used to study the
      impact of ion-channel and structural manipulations on the distributions of
      extracellular potentials on the heart and body surface. METHODS: A model of the
      mouse heart anatomy, fibre organization and torso geometry was constructed from
      DTMRI images. An anisotropic bidomain model, with a modified Pandit et al. model
      for the ionic currents, was used to represent the electrical properties of the
      tissue. Spatial heterogeneity in the ion currents was introduced by modulating
      the transient outward current. A sinus beat was simulated in hearts with
      different tissue and membrane properties and the extracellular potentials were
      computed at both the heart and body surface. RESULTS: The simulated transmembrane
      patterns in the heart, and the timing and morphology of the simulated ECG
      waveforms were consistent with experimental measurements. In addition, the
      patterns of activation and recovery and the waveforms of the corresponding ECG
      were found to be relatively insensitive to changes in cell type distribution and
      tissue anisotropy. CONCLUSION: Because of the small size of the heart, an
      integrative model of mouse electrophysiology can be simulated from cell to torso,
      enabling a new tool to study how extracellular signals might be used to detect
      molecular changes underlying an arrhythmogenic substrate.

PMID- 16102505
TI  - Effects of antiarrhythmic drug therapy on atrioventricular nodal function during
      atrial fibrillation in humans.
AB  - AIMS: To assess the effects of metoprolol and amiodarone on atrial and
      ventricular activity during atrial fibrillation (AF) in post-surgical patients,
      and to develop and use a mathematical model of the atrioventricular (AV) node
      during AF that incorporates parameters describing the properties of the AV node
      to evaluate the physiological basis of the drug effects. METHODS AND RESULTS: Ten
      post-surgical patients were evaluated where three received no medical therapy,
      three received metoprolol, three received amiodarone, and one received both
      metoprolol and amiodarone. The medications led to increases of 37-310 ms in the
      mean VV interval in treated patients, but much smaller changes in the mean AA
      intervals in the right and left atria. The mathematical model incorporating a
      random influence of the concealed conduction parameter was capable of reproducing
      the histograms of the VV intervals based on the input from the right atrium by
      systematically searching parameter space. CONCLUSIONS: Changes in the ventricular
      rate are mainly due to the alteration in the AV nodal properties rather than
      changes in the atrial rhythm. The medications can display differential effects on
      the physiological properties of the AV node, and therefore the mathematical model
      may help to identify novel pharmacological targets.

PMID- 16102506
TI  - Wavelength and vulnerability to atrial fibrillation: Insights from a computer
      model of human atria.
AB  - AIM: To explain the contradictory results related to the concept of critical
      cardiac wavelength in the initiation and perpetuation of atrial fibrillation
      (AF). METHODS: A biophysically based computer model was used to: (1) study the
      relationship between wavelength and AF perpetuation in the presence of multiple
      re-entrant wavelets, (2) evaluate the performance of different existing methods
      for wavelength estimation in the presence of different arrhythmogenic substrates,
      and (3) document the impact of either heterogeneities in refractoriness or the
      presence of a mother rotor on wavelength estimation. RESULTS: The simulations
      confirmed that the wavelength must be below a critical value for AF to be
      sustained, when the perpetuation mechanism relies on multiple re-entrant
      wavelets. The estimated value of wavelength was not the same for all methods
      tested and depended in part on the nature of the spatio-temporal organization of
      the AF dynamics. CONCLUSION: A priori information about the underlying wavelet
      dynamics is needed for a correct interpretation of the cardiac wavelength as
      estimated by the current clinical methods.

PMID- 16102507
TI  - Alternating conduction in the ischaemic border zone as precursor of reentrant
      arrhythmias: a simulation study.
AB  - AIMS: Here, we investigate the mechanisms underlying the onset of conduction
      related arrhythmias in a three-dimensional (3D) computational model of acute
      regional ischaemia. METHODS: Ischaemia was introduced by realistic gradients of
      potassium, pH, oxygen and electrical coupling in a 3D slab of ventricular tissue
      using the LRd model. We focused on a specific stage (10-15 min after occlusion)
      at which an intramural non-conductive ischaemic core (IC) surrounded by a border
      zone (BZ) has formed. RESULTS: At pacing frequencies greater than 4.5 Hz, we
      observed narrow areas (0.5 mm wide) of 2:1 conduction blocks at the periphery of
      the IC. As the pacing frequency increased, the area of block widened to 9 mm and
      gave rise to reentry at the periphery of the BZ. Alternating conduction blocks
      produced discordant action potential duration (APD) alternans throughout the slab
      and T-wave alternans in pseudo-ECG. Slowing the recovery of the calcium current
      broadened the range of pacing frequencies at which blocks were observed.
      Hyperkalaemia alone was sufficient to induce the alternating blocks. CONCLUSION:
      Computer modelling predicts that ischaemia-related arrhythmias are triggered by
      calcium-mediated alternating conduction blocks in the ischaemic border zone.
      Alternating conduction blocks lead to intramural reentry and APD alternans.

PMID- 16102508
TI  - Modelling of short QT syndrome in a heterogeneous model of the human ventricular
      wall.
AB  - AIMS: A percentage of sudden cardiac death events occur in individuals with
      structurally normal hearts due to an abnormality in the ion channel activity.
      While the majority of these hereditary syndromes are well-established, little is
      known about the significance of the short QT syndrome. METHODS: This study is
      based on discovered insights into the molecular basis of the originally described
      form of this disease. A biophysically detailed model of cellular
      electrophysiology was adapted to emulate the behaviour of cells affected by the
      short QT syndrome. Simulations were performed in single cell and homogeneous as
      well as heterogeneous anisotropic multi-cellular environment describing the human
      left ventricle. RESULTS: The short QT mutation increased the activity of the
      repolarizing outward potassium current I(Kr). The heterogeneous abbreviation of
      the action potential duration decreased the dispersion of repolarization in
      heterogeneous tissue. Repolarization was homogenized and the final repolarization
      was shifted to epicardial sites. The transmural ECG showed a shortened QT
      interval and a T wave with reduced amplitude. CONCLUSION: The altered
      characteristics of the mutant I(Kr) current were consistent with experimental
      findings. The heterogeneous reduction of the action potential duration and the
      reduced T wave amplitude need to be verified by measurements.

PMID- 16102509
TI  - New developments in a strongly coupled cardiac electromechanical model.
AB  - AIM: The aim of this study is to develop a coupled three-dimensional
      computational model of cardiac electromechanics to investigate fibre length
      transients and the role of electrical heterogeneity in determining left
      ventricular function. METHODS: A mathematical model of cellular electromechanics
      was embedded in a simple geometric model of the cardiac left ventricle.
      Electrical and mechanical boundary conditions were applied based on Purkinje
      fibre activation times and ventricular volumes through the heart cycle. The mono
      domain reaction diffusion equations and finite deformation elasticity equations
      were solved simultaneously through the full pump cycle. Simulations were run to
      assess the importance of cellular electrical heterogeneity on myocardial
      mechanics. RESULTS: Following electrical activation, mechanical contraction moves
      out through the wall to the circumferentially oriented mid-wall fibres, producing
      a progressively longitudinal and twisting deformation. This is followed by a more
      spherical deformation as the inclined epicardial fibres are activated. Mid-way
      between base and apex peak tensions and fibre shortening of 40 kPa and 5%,
      respectively, are generated at the endocardial surface with values of 18 kPa and
      12% at the epicardial surface. Embedding an electrically homogeneous cell model
      for the same simulations produced equivalent values of 36.5 kPa, 4% at the
      endocardium and 14 kPa, 13.5% at the epicardium. CONCLUSION: The substantial
      redistribution of fibre lengths during the early pre-ejection phase of systole
      may play a significant role in preparing the mid-wall fibres to contract. The
      inclusion of transmural heterogeneity of action potential duration has a marked
      effect on reducing sarcomere length transmural dispersion during repolarization.

PMID- 16102510
TI  - An ionic model of stretch-activated and stretch-modulated currents in rabbit
      ventricular myocytes.
AB  - AIMS: To develop an ionic model of stretch-activated and stretch-modulated
      currents in rabbit ventricular myocytes consistent with experimental
      observations, that can be used to investigate the role of these currents in
      intact myocardium. METHODS AND RESULTS: A non-specific cation-selective stretch
      activated current I(ns), was incorporated into the Puglisi-Bers ionic model of
      epicardial, endocardial and midmyocardial ventricular myocytes. Using the model,
      we predict a reduction in action potential duration at 20% repolarization
      (APD(20)) and action potential amplitude, an elevated resting transmembrane
      potential and either an increase or decrease in APD(90), depending on the
      reversal potential of I(ns). A stretch-induced decrease in I(K1) (70%), plus a
      small I(ns) current (g(ns) = 10 pS), results in a reduction in APD(20) and
      increase in APD(90), and a reduced safety factor for conduction. Increasing I(K1)
      (150%) plus a large I(ns) current (g(ns) = 40 pS), also leads to a reduction in
      APD(20) and increase in APD(90), but with a greater safety factor. Endocardial
      and midmyocardial cells appear to be the most sensitive to stretch-induced
      changes in action potential. The addition of the K(+)-specific stretch-activated
      current (SAC) I(Ko) results in action potential shortening. CONCLUSION:
      Transmural heterogeneity of I(Ko) may reduce repolarization gradients in intact
      myocardium caused by intrinsic ion channel densities, nonuniform strains and
      electrotonic effects.

PMID- 16102511
TI  - A membrane model of electrically remodelled atrial myocardium derived from in
      vivo measurements.
AB  - AIMS: Contemporary ionic-based membrane models are computationally expensive and
      are not intended to match the properties of a given experimental preparation. The
      aim of this work was to use measured restitution properties of electrically
      remodelled atrial tissue to develop a simplified membrane model based on the
      Fenton-Karma (FK) equations amenable to large-scale simulation of chronic atrial
      fibrillation (CAF). METHODS: Two membrane models, the FK-CAF and FK-CNTRL
      parameter sets, were developed to match action potential duration (APD) and
      conduction velocity (CV) restitution properties of rapid-pacing-induced
      electrically remodelled sheep atria and healthy atria, respectively. The models
      were tested by inducing reentry in a two-dimensional anisotropic monodomain and
      comparing the resulting cycle lengths (CL) with measured CLs. RESULTS: Parameters
      for the FK models were obtained that reproduced APD and CV restitution properties
      measured in the CAF and healthy sheep atria. Using the FK-CAF parameters, reentry
      was sustained in a 2.5 by 2.5 cm sheet with a CL = 91.0 +/- 3.0 ms. Reentry (CL =
      113.2 +/- 5.2 ms) could only be sustained in the FK-CNTRL model after the tissue
      was first activated at a fast rate (136.5 ms). CONCLUSIONS: The FK-CAF model is
      shown to approximate the restitution properties of remodelled sheep atria and can
      be used to simulate reentry with short CLs similar to those measured during AF
      episodes.

PMID- 16102512
TI  - Electroporation of the heart.
AB  - Defibrillation shocks are commonly used to terminate life-threatening
      arrhythmias. According to the excitation theory of defibrillation, such shocks
      are aimed at depolarizing the membranes of most cardiac cells resulting in
      resynchronization of electrical activity in the heart. If shock-induced changes
      in transmembrane potential are large enough, they can cause transient tissue
      damage due to electroporation. In this review evidence is presented that (a)
      electroporation of the heart tissue can occur during clinically relevant
      intensities of the external electrical field, and (b) electroporation can affect
      the outcome of defibrillation therapy; being both pro- and anti-arrhythmic.

PMID- 16102513
TI  - Cell and tissue responses to electric shocks.
AB  - AIM: Existing models of myocardial membrane kinetics have not been able to
      reproduce the experimentally-observed negative bias in the asymmetry of
      transmembrane potential changes (DeltaV(m)) induced by strong electric shocks.
      The goals of this study are (1) to demonstrate that this negative bias could be
      reproduced by the addition, to the membrane model, of electroporation and an
      outward current, I(a), part of the K(+) flow through the L-type Ca(2+)-channel,
      and (2) to determine how such modifications in the membrane model affect shock
      induced break excitation in a 2D preparation. METHODS AND RESULTS: We conducted
      simulations of shocks in bidomain fibres and sheets with membrane dynamics
      represented by the Luo-Rudy dynamic model (LRd'2000), to which electroporation
      (LRd + EP model) and the outward current, I(a), activated upon strong shock
      induced depolarization (aLRd model) was added. Assuming I(a) is a part of K(+)
      flow through the L-type Ca(2+)-channel enabled us to reproduce both the
      experimentally observed rectangularly-shaped positive DeltaV(m) and the value of
      near 2 of the negative-to-positive DeltaV(m) ratio. In the sheet, I(a) not only
      contributed to the negative bias in DeltaV(m) asymmetry at sites polarized by
      physical and virtual electrodes, but also restricted positive DeltaV(m).
      Electroporation, in its turn, was responsible for the decrease in cathode-break
      excitation threshold in the aLRd sheet, compared with the other two cases, as
      well as for the occurrence of the excitation after the shock-end rather than
      during the shock. CONCLUSIONS: The incorporation of electroporation and I(a) in a
      membrane model ensures match between simulation results and experimental data.
      The use of the aLRd model results in a lower threshold for shock-induced break
      excitation.

PMID- 16102514
TI  - Computer simulations of successful defibrillation in decoupled and non-uniform
      cardiac tissue.
AB  - AIM: The aim of the present study is to investigate the origin and effect of
      virtual electrode polarization in uniform, decoupled and non-uniform cardiac
      tissue during field stimulation. METHODS: A discrete bidomain model with active
      membrane behaviour was used to simulate normal cardiac tissue as well as cardiac
      tissue that is decoupled due to fibrosis and gap junction remodelling. Various
      uniform and non-uniform electric fields were applied to the external domain of
      uniform, decoupled and non-uniform resting cardiac tissue as well as cardiac
      tissue in which spiral waves were induced. RESULTS: Field stimulation applied on
      non-uniform tissue results in more virtual electrodes compared with uniform
      tissue. The spiral waves were terminated in decoupled tissue, but not in uniform,
      homogeneous tissue. By gradually increasing local differences in intracellular
      conductivities, the amount and spread of virtual electrodes increased and the
      spiral waves were terminated. CONCLUSION: Fast depolarization of the tissue after
      field stimulation may be explained by intracellular decoupling and spatial
      heterogeneity present in normal and pathological cardiac tissue. We demonstrated
      that termination of spiral waves by means of field stimulation can be achieved
      when the tissue is modelled as a non-uniform, anisotropic bidomain with active
      membrane behaviour.

PMID- 16102515
TI  - Treatment of epilepsy in adults: expert opinion, 2005.
AB  - RATIONALE: Over the past decade, there has been a proliferation of new therapies
      for the treatment of epilepsy. Faced with this growing list of options,
      clinicians must decide what therapy, or combination of therapies, is best for a
      given individual. Although controlled clinical trials exist for each treatment
      option, the answer to these questions may remain unclear. In 2000, a survey of
      expert opinion was done to address questions concerning which treatment options
      might be best in a number of clinical situations. We surveyed a group of US
      epileptologists again in 2004 and compared the results of the two surveys.
      METHODS: We sent a questionnaire on the treatment of adolescent and adult
      epilepsy syndromes to a group of opinion leaders in the field of epilepsy. The
      questions were formatted to simulate real-world clinical situations in the
      treatment of symptomatic localization related epilepsy (SLRE) and idiopathic
      generalized epilepsy (IGE). The experts were asked to rate treatment options
      based on a modified RAND 9-point scale (with "9" most appropriate and "1" least
      appropriate). Statistical analysis of data was performed as defined by the expert
      consensus method. The results were used to develop user-friendly recommendations
      concerning overall treatment strategies and choice of specific medications.
      RESULTS: Of the 48 experts to whom the survey was sent, 43 (90%) responded; 29
      (67%) of the respondents had also participated in the first survey. For initial
      monotherapy for IGE (generalized tonic-clonic [GTC], absence, and myoclonic
      seizures), valproate was rated as treatment of choice. For IGE-GTC seizures,
      lamotrigine and topiramate were also identified as usually appropriate for
      initial monotherapy. For IGE-absence seizures, ethosuximide was also a treatment
      of choice, and lamotrigine was usually appropriate. For SLRE, the experts were
      again asked to rate treatment options based on seizure type: simple partial
      seizures (SPS), complex partial seizures (CPS), and secondarily generalized tonic
      clonic seizures (SGTC). In SLRE-SPS and SLRE-SGTC, carbamazepine and
      oxcarbazepine were treatments of choice, with lamotrigine and levetiracetam also
      usually appropriate. In SLRE-CPS, carbamazepine, lamotrigine. and oxcarbazepine
      were treatments of choice, while levetiracetam was also usually appropriate. For
      women who are pregnant or trying to conceive, lamotrigine was treatment of choice
      for both syndrome types. In the elderly, whether medically stable or ill, the
      treatment of choice was lamotrigine, while levetiracetam was also usually
      appropriate (along with gabapentin for persons with comorbid medical illness). In
      persons with HIV and epilepsy, lamotrigine and levetiracetam were usually
      appropriate. In people with both epilepsy syndromes who have depression,
      lamotrigine was treatment of choice. In a person with seizures and renal disease,
      lamotrigine was usually appropriate for both syndromes, with valproate also
      usually appropriate for IGE. In patients with hepatic disease, levetiracetam and
      lamotrigine were usually appropriate for IGE; in SLRE, levetiracetam was
      treatment of choice, with gabapentin also usually appropriate. CONCLUSIONS:
      Although the panel of experts reached consensus on many treatment options, there
      are limitations to these types of data. Despite this, the expert consensus method
      concisely summarizes expert opinion, and this opinion may be helpful in
      situations in which the medical literature is scant or lacking. The information
      in this report should be evaluated in conjunction with evidence-based findings.

PMID- 16102516
TI  - Detection of a novel population of fetal thymocytes characterized by preferential
      emigration and a TCRgammadelta+ T cell fate after dioxin exposure.
AB  - T cell maturation into TCRalphabeta(+) or TCRgammadelta(+) cells from common
      immature CD4(-)CD8(-)(DN) precursors occurs in the thymus, and is controlled
      through ordered regulation of genes. The aryl hydrocarbon receptor (AHR), a
      latent cytoplasmic transcription factor, affects thymocyte maturation and
      differentiation at several stages, also including DN cells. We analyzed in murine
      fetal thymus organ cultures (FTOC) the outcome of AHR-signaling and found a
      higher frequency of DN TCRgammadelta(+) cells in the presence of the AHR
      activating ligand TCDD. We detected a novel population of CD25(int/lo)CD44(hi)
      cells associated with preferential emigration and a TCRgammadelta(+) T cell fate
      of thymocytes. Sorted DN TCRgammadelta(+) emigrants could proliferate if IL-2 was
      available. Moreover, they suppressed the proliferation of co-cultivated,
      activated CD4(+) T cells. Gene expression profiles of purified DN emigrants from
      TCDD*FTOC revealed 295 modulated genes, 10% of which are genes of the immune
      system. For instance, RAG-1, TdT, and Gfi-1 were downregulated, yet genes
      indicative of mature thymocytes were upregulated. In conclusion, we have detected
      changes in the differentiation programme of fetal DN thymocytes after ligand
      activation of the AHR. In particular, we observed a higher frequency of DN
      TCRgammadelta(+) cells with high emigration potential, and possible regulatory
      functions.

PMID- 16102517
TI  - Anti-inflammatory activity of Seabuckthorn (Hippophae rhamnoides) leaves.
AB  - Immunomodulatory activity of Seabuckthorn (SBT) leaf extract was evaluated in
      adjuvant induced arthritis (AIA) rat model. Inflammation was induced by injecting
      Complete Freund's Adjuvant (CFA) in the right hind paw of rats. SBT extract was
      administered intraperitoneally to treat the inflammation. The extent of
      inflammation and treatment response was evaluated by clinical analysis,
      scintigraphic visualization using technitium-99m-glutathione (Tc99m-GSH) and
      lymphocyte proliferation. Serial evaluation was carried out on days 1, 7, 14, 21
      and 28 after creation of inflammation. The Tc99m-GSH uptake in the inflamed leg
      was compared with the normal contralateral leg of the same animal. The
      measurements were done by obtaining scintigraphic images using gamma camera and
      an online computer. Both qualitative and quantitative evaluation of radiotracer
      accumulation was considered to evaluate the anti-inflammatory response. The
      lymphocyte proliferation study revealed cellular immunosuppression during the
      early phase of the disease. Administration of SBT extract on the same day or 5
      days prior to inflammatory insult into the joint, significantly reduced the
      inflammation as compared to the untreated animals in a dose dependent manner.
      These observations suggest that the SBT leaf extract has a significant anti
      inflammatory activity and has the potential for the treatment of arthritis.

PMID- 16102518
TI  - Transgene expression enhancement in T-lymphoma cell lines.
AB  - In transfection protocols, the expression levels of the transgene is important to
      define, still is difficult to obtain in certain cell lines such as those derived
      from T-lymphoma cells. In this study we evaluate transgene expression kinetics in
      the presence and absence of two well known transcription activators such as
      phorbol-12-myristate13-acetate (PMA) and Ionomicin (IO). Three murine T lymphoma
      cell lines (LBC, EL4 and BW5147) were transfected by electroporation using green
      fluorescent protein (GFP) as a reporter gene and analyzed by flow cytometry.
      Addition of PMA/IO resulted in a significant increase of the Mean Fluorescence
      Intensity but not in GFP-positive cell percentages, either in transient or stable
      transfected LBC and EL4 cells. Remarkable, BW5147 cells showed low GFP induction
      with a significant increment only in stable transfected cells. Our results
      demonstrated that CMV promoter activity can be enhanced in transfected lymphoma
      cells by PMA/IO suggesting that transgene expression levels can be optimized by
      means of the use of transcription activators.

PMID- 16102519
TI  - Immune response to Saccharomyces cerevisiae mannan conjugate in mice.
AB  - Mannan, the surface polysaccharide antigen of Saccharomyces cerevisiae was
      partially oxidized and conjugated to a protein carrier. Prepared conjugate was
      immunogenic in mice and re-injection elicited significant increase of anti-S.
      cerevisiae specific IgG and IgM serum antibodies. There was somewhat less
      increase in IgM serum antibodies. Serum distribution of IgG subclasses,
      especially IgG(2(a+b)):IgG(1) ratio throughout the immunization demonstrated
      effective Th1 predominance of immune response. Newly synthesized S. cerevisiae
      mannan conjugate could be considered as a perspective vaccine candidate for
      preventive immunomodulation treatment.

PMID- 16102520
TI  - IL-10-dependent down-regulation of MHC class II expression level on monocytes by
      peritoneal fluid from endometriosis patients.
AB  - Endometriosis is a gynecologic disorder characterized by the ectopic growth of
      misplaced endometrial cells. Moreover, immunological abnormalities of cell
      mediated and humoral immunity may be associated with the pathogenesis of
      endometriosis. The effects of peritoneal fluid (PF) from endometriosis patients
      on the expression levels of MHC class II and costimulatory molecules on the cell
      surfaces of monocytes were investigated. Compared to the PF of controls, the
      addition of 10% PF (n=10) from patients with endometriosis to culture medium
      significantly reduced the percentage of MHC class II-positive cells in cultures
      of a THP-1, monocytic cell line at 48 h. The effect of endometriosis patient PF
      (EPF) was dose-dependent, and similar effect was observed in peripheral blood
      monocytes. An inverse correlation was found between MHC class II expression level
      and IL-10 concentration in EPF (r=-0.518; p=0.019) and in the supernatant of
      peripheral blood monocyte cultured in EPF (r=-0.459; p=0.042) (n=20). The
      expression levels of costimulatory molecules (CD80 and CD86), but not of CD54 and
      B7-H1, were down-regulated by EPF. The mRNA level of HLA-DR was unaffected by EPF
      but protein level was reduced by EPF. Neutralizing IL-10 antibody abrogated MHC
      class II down-regulation on monocytes, which had been induced by EPF. However, in
      a functional assay, monocytes treated with EPF failed to stimulate T cell in
      mixed leukocyte reaction, although T cell proliferation was increased with EPF
      treated monocytes and Staphylococcus enterotoxin B. These results suggest that
      MHC class II expression level on monocytes is down-regulated by EPF, but the cell
      stimulatory ability of monocytes does not coincide with MHC class II expression
      level.

PMID- 16102521
TI  - Characterisation of the in vitro modulation of splenocyte proliferation by non
      4,5-epoxymorphinan opioids.
AB  - Opioids, such as morphine, can directly alter immune function via receptors
      expressed on immunocompetent cells. However, several studies have questioned the
      classical opioid nature of this change in immune response. Therefore, it is
      unclear how opioids that are not from the same structural class as morphine (4,5
      epoxymorphinan), will modulate the immune system, if they do not behave in a
      classical opioid manner. Therefore, the aim of this study was to investigate the
      in vitro modulatory effects of a range of non-4,5-epoxymorphinan opioids on
      splenocyte proliferation and compare the response characteristics to their
      central opioid characteristics. The modulation of concanavalin A stimulated mouse
      splenocyte proliferation by non-4,5-epoxymorphinan opioids resulted in three
      types of responses: an inhibitory concentration-response curve (e.g. methadone,
      inhibitory EC(50)=79.4 microM), an inverted bell shaped curve (e.g. fentanyl,
      inhibitory EC(50)=0.06 microM) and an induction concentration response curve
      (e.g. nor-binaltorphimine, induction EC(50)=0.16 microM). Non-stereoselectivity,
      naloxone-insensitivity, naloxone-sensitivity and non-classical opioid rank order
      of effect were all observed. These data support the non-classical opioid nature
      of direct opioid modulation of splenocyte proliferation.

PMID- 16102522
TI  - Effects of central and peripheral depletion of serotonergic system on carrageenan
      induced paw oedema.
AB  - The role of serotonergic system was investigated on peripheral inflammation
      induced by intraplantary injection of carrageenan. Para-chlorophenylalanine
      (PCPA) was administered intracerebroventriculary (50, 100 microg/rat) or
      intraperitoneally (150 mg/kg, 3 days) and 2 or 24 h later, respectively,
      inflammation was induced by injection of carrageenan. Paw oedema was decreased
      significantly in PCPA-treated (100 microg/rat, i.c.v.) rats compared to control
      groups. Injection of exogenous serotonin (i.c.v.) by dose of 0.70 nmol/10
      microl/rat, but not the dose of 0.35 nmol/10 microl/rat, 15 min after induction
      of inflammation completely reversed the anti-inflammatory effects of PCPA.
      Myeloperoxidase activity in inflamed paws was reduced significantly in groups
      received PCPA (either i.c.v. or i.p.) compared to controls. Exogenous serotonin
      (0.70 nmol/10 microl/rat) reduced inflammatory response when injected (i.c.v.) 30
      min before or 30 min after the induction of inflammation. Injection of serotonin
      at the time of induction of inflammation had no inflammatory/anti-inflammatory
      effect. These results suggest that serotonin, as a neurotransmitter in central
      nervous system, may be involved in modulating peripheral inflammation.

PMID- 16102523
TI  - Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but
      not by the receptors of other members of IL-6 cytokine family.
AB  - To characterize the biological activity of tocilizumab, a humanized anti-human
      interleukin-6 receptor (IL-6R) monoclonal antibody, we examined its binding
      activity to both soluble IL-6R (sIL-6R) and membrane bound IL-6R (mIL-6R) and its
      neutralizing activity to other IL-6 family cytokines. ELISA assay demonstrated
      that tocilizumab bound to sIL-6R and inhibited IL-6 binding to sIL-6R in a dose
      dependent manner. The dissociation constant (Kd value) for IL-6R was determined
      to be 2.54+/-0.12 nmol/L by Scatchard analysis. In addition, tocilizumab had the
      ability to dissociate IL-6 and sIL-6R from their preformed complex. The immune
      complex of tocilizumab and sIL-6R did not transmit signaling. Moreover,
      tocilizumab suppressed the IL-6/sIL-6R complex-induced proliferation of human
      gp130-transfected cell, BAF-h130. In addition, tocilizumab had the ability to
      bind to human IL-6R expressing COS-7 cells and to suppress the growth of the IL-6
      dependent myeloma cell line, KPMM2. Finally, to analyze the specificity of this
      antibody, the effects on signal transduction of IL-6 family cytokines such as
      interleukin-11 (IL-11), oncostatin M (OSM), leukemia inhibitory factor (LIF), and
      ciliary neurotrophic factor (CNTF) were examined using murine transfectant cell
      lines (BaF/IL-6R, BaF/IL-11R, BaF/OSMR, BaF/LIFR and BaF/CNTFR) that proliferate
      depending on IL-6, IL-11, OSM, LIF and human CNTF, respectively. Tocilizumab
      inhibited the proliferation of BaF/IL-6R induced by IL-6, but did not inhibit the
      proliferation of BaF/IL-11R, BaF/OSMR, BaF/LIFR and BaF/CNTFR cells induced by
      their corresponding cytokines. These lines of evidence indicate that tocilizumab
      is able to bind to both sIL-6R and mIL-6R and to inhibit IL-6 binding to its
      receptors, leading to the blockade of the IL-6 signaling through both sIL-6R and
      mIL-6R, but not block the signaling of other IL-6 family cytokines.

PMID- 16102524
TI  - Electroencephalogram and behavioral changes induced by histamine application into
      the nasal cavity and the effects of some H(1)-receptor antagonists.
AB  - The present study was performed to measure the olfactory bulb with an
      electroencephalogram (EEG) to investigate the relationship between the EEG and
      behavioral changes of rats induced by the topical application of histamine into
      the nasal cavity. The effects of some H(1)-receptor antagonists on the EEG and
      behavioral changes induced by histamine were also studied. The topical
      application of histamine into the nasal cavity resulted in a significant and dose
      dependent increase in the incidence of sneezing and nasal rubbing. The EEG spike
      at the olfactory bulb was also observed to be in parallel with the sneezing. In
      addition, there was an intimate relationship between the EEG spike and sneezing;
      however, no correlation was observed between the EEG spike and nasal rubbing. All
      the H(1)-receptor antagonists used in the present study caused an inhibition not
      only of sneezing but also of the EEG spike at the same dose level. These results
      suggested that the EEG spike observed in the olfactory bulb is an objective and
      reliable indication of sneezing induced by allergic rhinitis.

PMID- 16102526
TI  - The determination of 2beta-(3-hydroxypropoxy)-1alpha,25-dihydroxy vitamin D3 (ED
      71) in human serum by high-performance liquid chromatography-electrospray tandem
      mass spectrometry.
AB  - A liquid chromatography-electrospray ionization tandem mass spectrometric (LC/ESI
      MS/MS) method for the determination of 2beta-(3-hydroxypropoxy)-1alpha,25
      dihydroxy vitamin D3 (ED-71) in human serum has been developed. ED-71 in human
      serum was extracted using two solid-phase extraction steps on Bond Elut C18 and
      NH2 cartridge. The separation of ED-71 and preED-71 isomer was attained by LC
      using 2 mmol/L ammonium acetate-methanol (15:85, v/v) as a mobile phase on a
      Symmetry C18 column (5 microm, 150 mm x 2.1mm i.d.). ESI-MS/MS analysis was
      operated using selected reaction monitoring (SRM) in positive ion mode. The
      method achieved a lower limit of quantitation of 25 pg/mL. The calibration curve
      (25-3200 pg/mL) gave acceptable linearity (r>0.9964). Intra-assay precision
      ranged from 2.3 to 9.7%. Inter-assay precision ranged from 1.0 to 3.4%. The
      accuracy was within 90.8-107.0%. This highly sensitive and reproducible method is
      able to determine only biologically active ED-71 by separating it from preED-71,
      which is considered to be applicable for the determination of serum samples from
      pharmacokinetic studies in human.

PMID- 16102527
TI  - Apoer2: a reelin receptor to remember.
AB  - The extracellular protein Reelin is crucial for neuronal positioning during brain
      development, but its expression persists long after cell migration is completed.
      In this issue of Neuron, Beffert et al. demonstrate that Reelin exerts an
      additional function in the mature brain, to modulate synaptic plasticity and to
      favor memory formation. This activity is carried out exquisitely by the Apoer2
      receptor and critically requires the presence of an alternatively spliced exon.
      This exon encodes an intracellular domain that interacts with postsynaptic
      proteins and promotes binding and phosphorylation of NMDA receptors.

PMID- 16102528
TI  - A truffle in the mouth is worth two in the bush: odor localization in the human
      brain.
AB  - It is widely thought that locating the source of a smell is an ability best left
      to nonhuman members of the animal kingdom. In this issue of Neuron, two
      complementary articles highlight the neural mechanisms underlying the
      localization of an odor, either to the left or right side of the nose (Porter et
      al.) or to the inside or outside of the mouth (Small et al.). Together, these
      studies validate the idea that the human brain is equipped with the apparatus
      necessary to pinpoint the location of an odor source.

PMID- 16102529
TI  - Contrast gain in the brain.
AB  - Human sensory systems have the remarkable ability of adjusting sensitivity to the
      surrounding environment. In this issue of Neuron, Gardner and colleagues used
      fMRI to show how the visual system shifts its sensitivity to contrast. This
      process may be helpful for keeping the appearance of contrast constant across a
      range of spatial frequencies.

PMID- 16102530
TI  - Nosology of Parkinson's disease: looking for the way out of a quagmire.
AB  - The discovery of SNCA mutations pathogenic for autosomal-dominant Lewy body
      Parkinson's disease (PD) in 1997 heralded a revolution in understanding the
      molecular and genetic basis of PD. Indeed, it now is clear that Lewy body PD is
      one of many neurodegenerative parkinsonian disorders that result from
      nigrostriatal degeneration caused by diverse mechanisms. However, to capitalize
      on these new insights and facilitate efforts to improve the diagnosis and therapy
      of neurodegenerative movement disorders, it is timely to define a nosology for
      these diseases that is based on their genetic and molecular underpinnings, as
      proposed here.

PMID- 16102531
TI  - Social circuits: peptidergic regulation of mammalian social behavior.
AB  - Mammals have developed patterns of social relationships that enhance the survival
      of individuals and maximize the reproductive success of species. Although social
      stimuli and social responses are highly complex, recent studies are providing
      substantial insights into their neural substrates. Neural pathways employing the
      nonapeptides vasopressin and oxytocin play a particularly prominent role both in
      social recognition and the expression of appropriate social responses. New
      insights into social neuroscience are discussed, along with the relevance of this
      rapidly developing field to human relationships and disease processes.

PMID- 16102532
TI  - Hippocalcin functions as a calcium sensor in hippocampal LTD.
AB  - It is not fully understood how NMDAR-dependent LTD causes Ca(2+)-dependent
      endocytosis of AMPARs. Here we show that the neuronal Ca(2+) sensor hippocalcin
      binds the beta2-adaptin subunit of the AP2 adaptor complex and that along with
      GluR2 these coimmunoprecipitate in a Ca(2+)-sensitive manner. Infusion of a
      truncated mutant of hippocalcin (HIP(2-72)) that lacks the Ca(2+) binding domains
      prevents synaptically evoked LTD but has no effect on LTP. These data indicate
      that the AP2-hippocalcin complex acts as a Ca(2+) sensor that couples NMDAR
      dependent activation to regulated endocytosis of AMPARs during LTD.

PMID- 16102533
TI  - Error-related negativity predicts reinforcement learning and conflict biases.
AB  - The error-related negativity (ERN) is an electrophysiological marker thought to
      reflect changes in dopamine when participants make errors in cognitive tasks. Our
      computational model further predicts that larger ERNs should be associated with
      better learning to avoid maladaptive responses. Here we show that participants
      who avoided negative events had larger ERNs than those who were biased to learn
      more from positive outcomes. We also tested for effects of response conflict on
      ERN magnitude. While there was no overall effect of conflict, positive learners
      had larger ERNs when having to choose among two good options (win/win decisions)
      compared with two bad options (lose/lose decisions), whereas negative learners
      exhibited the opposite pattern. These results demonstrate that the ERN predicts
      the degree to which participants are biased to learn more from their mistakes
      than their correct choices and clarify the extent to which it indexes decision
      conflict.

PMID- 16102534
TI  - The V1a vasopressin receptor is necessary and sufficient for normal social
      recognition: a gene replacement study.
AB  - Vasopressin modulates many social and nonsocial behaviors, including
      emotionality. We have previously reported that male mice with a null mutation in
      the V1a receptor (V1aR) exhibit a profound impairment in social recognition and
      changes in anxiety-like behavior. Using site-specific injections of a V1aR
      specific antagonist, we demonstrate that the lateral septum, but not the medial
      amygdala, is critical for social recognition. Reexpressing V1aR in the lateral
      septum of V1aR knockout mice (V1aRKO) using a viral vector resulted in a complete
      rescue of social recognition. Furthermore, overexpression of the V1aR in the
      lateral septum of wild-type (wt) mice resulted in a potentiation of social
      recognition behavior and a mild increase in anxiety-related behavior. These
      results demonstrate that the V1aR in the lateral septum plays a critical role in
      the neural processing of social stimuli required for complex social behavior.

PMID- 16102535
TI  - Regulation of EphA 4 kinase activity is required for a subset of axon guidance
      decisions suggesting a key role for receptor clustering in Eph function.
AB  - Signaling by receptor tyrosine kinases (RTKs) is mediated by their intrinsic
      kinase activity. Typically, kinase-activating mutations result in ligand
      independent signaling and gain-of-function phenotypes. Like other RTKs, Ephs
      require kinase activity to signal, but signaling by Ephs in vitro also requires
      clustering by their membrane bound ephrin ligands. The relative importance of Eph
      kinase activity and clustering for in vivo functions is unknown. We find that
      knockin mice expressing a mutant form of EphA4 (EphA4(EE)), whose kinase is
      constitutively activated in the absence of ephrinB ligands, are deficient in the
      development of thalamocortical projections and some aspects of central pattern
      generator rhythmicity. Surprisingly, other functions of EphA4 were regulated
      normally by EphA4(EE), including midline axon guidance, hindlimb locomotion, in
      vitro growth cone collapse, and phosphorylation of ephexin1. These results
      suggest that signaling of Eph RTKs follows a multistep process of induced kinase
      activity and higher-order clustering different from RTKs responding to soluble
      ligands.

PMID- 16102536
TI  - Farnesylation of retinal transducin underlies its translocation during light
      adaptation.
AB  - G proteins are posttranslationally modified by isoprenylation: either
      farnesylation or geranylgeranylation. The gamma subunit of retinal transducin
      (Talpha/Tbetagamma) is selectively farnesylated, and the farnesylation is
      required for light signaling mediated by transducin in rod cells. However,
      whether and how this selective isoprenylation regulates cellular functions remain
      poorly understood. Here we report that knockin mice expressing geranylgeranylated
      Tgamma showed normal rod responses to dim flashes under dark-adapted conditions
      but exhibited impaired properties in light adaptation. Of note,
      geranylgeranylation of Tgamma suppressed light-induced transition of Tbetagamma
      from membrane to cytosol, and also attenuated its light-dependent translocation
      from the outer segment to the inner region, an event contributing to retinal
      light adaptation. These results indicate that, while the farnesylation of
      transducin is interchangeable with the geranylgeranylation in terms of the light
      signaling, the selective farnesylation is important for visual sensitivity
      regulation by providing sufficient but not excessive membrane anchoring of
      Tbetagamma.

PMID- 16102537
TI  - Fast adaptation in vestibular hair cells requires myosin-1c activity.
AB  - In sensory hair cells of the inner ear, mechanical amplification of small stimuli
      requires fast adaptation, the rapid closing of mechanically activated
      transduction channels. In frog and mouse vestibular hair cells, we found that the
      rate of fast adaptation depends on both channel opening and stimulus size and
      that it is modeled well as a release of a mechanical element in series with the
      transduction apparatus. To determine whether myosin-1c molecules of the
      adaptation motor are responsible for the release, we introduced the Y61G mutation
      into the Myo1c locus and generated mice homozygous for this sensitized allele.
      Measuring transduction and adaptation in the presence of NMB-ADP, an allele
      specific inhibitor, we found that the inhibitor not only blocked slow adaptation,
      as demonstrated previously in transgenic mice, but also inhibited fast
      adaptation. These results suggest that mechanical activity of myosin-1c is
      required for fast adaptation in vestibular hair cells.

PMID- 16102538
TI  - Co-assembly of two GluR6 kainate receptor splice variants within a functional
      protein complex.
AB  - Kainate receptors (KAR) are composed of several distinct subunits and splice
      variants, but the functional relevance of this diversity remains largely unclear.
      Here we show that two splice variants of the GluR6 subunit, GluR6a and GluR6b,
      which differ in their C-terminal domains, do not show distinct functional
      properties, but coassemble as heteromers in vitro and in vivo. Using a proteomic
      approach combining affinity purification and MALDI-TOF mass spectrometry, we
      found that GluR6a and GluR6b interact with two distinct subsets of cytosolic
      proteins mainly involved in Ca(2+) regulation of channel function and
      intracellular trafficking. Guided by these results, we provide evidence that the
      regulation of native KAR function by NMDA receptors depends on the
      heteromerization of GluR6a and GluR6b and interaction of calcineurin with GluR6b.
      Thus, GluR6a and GluR6b bring in close proximity two separate subsets of
      interacting proteins that contribute to the fine regulation of KAR trafficking
      and function.

PMID- 16102539
TI  - Modulation of synaptic plasticity and memory by Reelin involves differential
      splicing of the lipoprotein receptor Apoer2.
AB  - Apolipoprotein E receptor 2 (Apoer2), a member of the LDL receptor gene family,
      and its ligand Reelin control neuronal migration during brain development. Apoer2
      is also essential for induction of long-term potentiation (LTP) in the adult
      brain. Here we show that Apoer2 is present in the postsynaptic densities of
      excitatory synapses where it forms a functional complex with NMDA receptors.
      Reelin signaling through Apoer2 markedly enhances LTP through a mechanism that
      requires the presence of amino acids encoded by an exon in the intracellular
      domain of Apoer2. This exon is alternatively spliced in an activity-dependent
      manner and is required for Reelin-induced tyrosine phosphorylation of NMDA
      receptor subunits. Mice constitutively lacking the exon perform poorly in
      learning and memory tasks. Thus, alternative splicing of Apoer2, a novel
      component of the NMDA receptor complex, controls the modulation of NMDA receptor
      activity, synaptic neurotransmission, and memory by Reelin.

PMID- 16102540
TI  - Brain mechanisms for extracting spatial information from smell.
AB  - Forty years ago, von Bekesy demonstrated that the spatial source of an odorant is
      determined by comparing input across nostrils, but it is unknown how this
      comparison is effected in the brain. To address this, we delivered odorants to
      the left or right of the nose, and contrasted olfactory left versus right
      localization with olfactory identification during brain imaging. We found nostril
      specific responses in primary olfactory cortex that were predictive of the
      accuracy of left versus right localization, thus providing a neural substrate for
      the behavior described by von Bekesy. Additionally, left versus right
      localization preferentially engaged a portion of the superior temporal gyrus
      previously implicated in visual and auditory localization, suggesting that
      localization information extracted from smell was then processed in a convergent
      brain system for spatial representation of multisensory inputs.

PMID- 16102541
TI  - Differential neural responses evoked by orthonasal versus retronasal odorant
      perception in humans.
AB  - Odors perceived through the mouth (retronasally) as flavor are referred to the
      oral cavity, whereas odors perceived through the nose (orthonasally) are referred
      to the external world. We delivered vaporized odorants via the orthonasal and
      retronasal routes and measured brain response with fMRI. Comparison of retronasal
      versus orthonasal delivery produced preferential activity in the mouth area at
      the base of the central sulcus, possibly reflecting olfactory referral to the
      mouth, associated with retronasal olfaction. Routes of delivery produced
      differential activation in the insula/operculum, thalamus, hippocampus, amygdala,
      and caudolateral orbitofrontal cortex in orthonasal > retronasal and in the
      perigenual cingulate and medial orbitofrontal cortex in retronasal > orthonasal
      in response to chocolate, but not lavender, butanol, or farnesol, so that an
      interaction of route and odorant may be inferred. These findings demonstrate
      differential neural recruitment depending upon the route of odorant
      administration and suggest that its effect is influenced by whether an odorant
      represents a food.

PMID- 16102543
TI  - Geriatric psychiatry: coming of age in America.

PMID- 16102542
TI  - Contrast adaptation and representation in human early visual cortex.
AB  - The human visual system can distinguish variations in image contrast over a much
      larger range than measurements of the static relationship between contrast and
      response in visual cortex would suggest. This discrepancy may be explained if
      adaptation serves to re-center contrast response functions around the ambient
      contrast, yet experiments on humans have yet to report such an effect. By using
      event-related fMRI and a data-driven analysis approach, we found that contrast
      response functions in V1, V2, and V3 shift to approximately center on the
      adapting contrast. Furthermore, we discovered that, unlike earlier areas, human
      V4 (hV4) responds positively to contrast changes, whether increments or
      decrements, suggesting that hV4 does not faithfully represent contrast, but
      instead responds to salient changes. These findings suggest that the visual
      system discounts slow uninformative changes in contrast with adaptation, yet
      remains exquisitely sensitive to changes that may signal important events in the
      environment.

PMID- 16102544
TI  - Aging-related diagnostic variations: need for diagnostic criteria appropriate for
      elderly psychiatric patients.
AB  - It is commonly thought and taught that most psychiatric disorders other than
      dementia are much less prevalent among the elderly than among younger adults.
      This perception is based on a relatively small number of published epidemiologic
      investigations of the incidence and prevalence of mental illnesses in elderly
      populations. Most of these studies have had a number of methodologic problems,
      including improper definitions and diagnostic criteria for older persons. A
      likely consequence of these misconceptions is that clinically significant and
      potentially treatable mental illnesses might be overlooked, misdiagnosed, and
      mistreated in elderly patients. Studies in community samples suggest that many
      older adults who experience clinically significant psychopathology do not fit
      easily into our existing nomenclature, and yet are disabled. There is a need to
      develop aging-appropriate diagnostic criteria for major psychiatric disorders. In
      this article, we discuss the potential causes of this diagnostic confusion. Four
      specific classes of disorders-mood (specifically depressive) disorders,
      schizophrenia (and related psychotic disorders), anxiety disorders, and substance
      use disorders-are discussed as examples. Finally, we suggest some future steps
      for clarifying this diagnostic confusion.

PMID- 16102545
TI  - The impact of psychosocial factors on late-life depression.
AB  - Mental illnesses in later life are multidimensional phenomena that occur in
      interpersonal, psychosocial, and biological contexts. With depression used as an
      example, the purpose of this article is to review how psychosocial variables
      contribute to the onset and maintenance of depression in late life, as well as
      influence treatment outcomes. Particular issues discussed are how these variables
      can be modified to prevent the onset and relapse of depression, how nonmodifiable
      risk factors can be addressed to prevent onset and relapse, and how research in
      this area needs to evolve to improve prevention and treatment.

PMID- 16102546
TI  - Actigraphy in patients with seasonal affective disorder and healthy control
      subjects treated with light therapy.
AB  - BACKGROUND: Abnormalities of the circadian rest-activity cycle are hypothesized
      to accompany the clinical picture of seasonal affective disorder (SAD). The
      purpose of this study was to investigate if bright light therapy (BLT) is able to
      reverse these disturbances. METHODS: Seventeen SAD outpatients and 17 sex- and
      age-matched healthy control subjects were treated with BLT administered in the
      morning for 4 weeks. Activity levels were measured with wrist actigraphy.
      RESULTS: SAD patients had 33% lower total (p = .031) and 43% lower daylight
      activity (p = .006) in week 1 compared with control subjects. The relative
      amplitude of the sleep-wake cycle was attenuated by 6% in patients (p = .025);
      they were phase delayed by 55 minutes (p = .023) and had significantly lower
      sleep efficiency (p = .030). Total (p = .002) and daylight activity (p = .001)
      increased after 4 weeks of treatment in SAD patients. Moreover, BLT led to
      increase of relative amplitude (p = .005), advance of delayed rhythms (p = .036),
      and improved sleep efficiency (p = .011) in patients. Intradaily stability,
      measuring the strength of coupling of the rhythm to external zeitgebers,
      increased by 9% both in patients and healthy control subjects (p = .032).
      CONCLUSIONS: Treatment with BLT normalizes disturbed activity patterns and
      restores circadian rhythms in SAD patients. BLT might also stabilize the
      circadian rhythm in nondepressed individuals during the fall-winter season.

PMID- 16102547
TI  - Enhanced cortical dopamine output and antipsychotic-like effect of raclopride
      with adjunctive low-dose L-dopa.
AB  - BACKGROUND: Clozapine shows superior efficacy in schizophrenia and enhances
      prefrontal dopamine (DA) output like other atypical, but not typical,
      antipsychotic drugs (APDs). Clinical data also suggest an improved effect of
      typical APDs in schizophrenia by adjunctive treatment with low doses of 3,4
      dihydroxyphenylalanine (L-dopa), but experimental support is scarce, and the
      underlying mechanisms are poorly understood. METHODS: Antipsychotic efficacy of
      the D2 antagonist raclopride with or without adjunctive treatment with a low dose
      of L-dopa was assessed with the conditioned avoidance response paradigm.
      Extrapyramidal side effects were scored by the catalepsy test. Finally, in vivo
      microdialysis was used to measure DA efflux in the prefrontal cortex and the
      nucleus accumbens. RESULTS: A low dose of L-dopa (3 mg/kg) combined with
      benserazide, an inhibitor of peripheral DOPA decarboxylase, significantly
      enhanced the antipsychotic-like effect of raclopride without any associated
      catalepsy. L-dopa/benserazide alone had no effect. In contrast to raclopride
      alone, combined L-dopa/raclopride also produced a much larger increase in DA
      output in the prefrontal cortex than in the nucleus accumbens. CONCLUSIONS: These
      data support the clinical observation that low-dose L-dopa might improve the
      effect of typical APDs in schizophrenia and indicate that increased prefrontal DA
      output per se enhances the antipsychotic effect of typical APDs.

PMID- 16102548
TI  - Depo-Provera's black box: time to reconsider?

PMID- 16102549
TI  - Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive
      formulations: the vaginal ring, the transdermal patch and an oral contraceptive.
AB  - This open-label, randomized study compared the pharmacokinetics of
      ethinylestradiol (EE) from the contraceptive vaginal ring NuvaRing (15 microg
      EE/day), the transdermal patch (20 microg EE/day) and a combined oral
      contraceptive (COC) containing 30 microg EE. After 2-8 weeks of synchronization
      by COC treatment, subjects were randomized to 21 days of treatment with NuvaRing,
      patch or COC. Analysis of area under the EE concentration-versus-time curve (AUC)
      during 21 days of treatment showed that exposure to EE in the NuvaRing group was
      3.4 times lower than in the patch group (p < .05) and 2.1 times lower than in the
      pill group (p < .05). Serum EE levels of subjects showed much lower variation
      with NuvaRing than with the patch or the COC. Thus, exposure to EE was
      significantly lower with NuvaRing than with the patch and pill methods,
      demonstrating that NuvaRing is a low-estrogen-dose contraceptive method that also
      results in low estrogen exposure.

PMID- 16102550
TI  - Safety of mifepristone abortions in clinical use.
AB  - OBJECTIVES: Extensive data from clinical trials document mifepristone's safety
      and efficacy for induced abortion, but less information is available about its
      safety in routine clinical use. METHODS: Data on mifepristone abortion use from
      the Planned Parenthood Federation of America, the largest provider of
      mifepristone abortion in the United States, from 2001 through the first quarter
      of 2004 were collected using a centralized reporting system. Over the study
      period, 95,163 mifepristone abortions were provided. Reportable events are
      complications requiring inpatient or outpatient hospital treatment. RESULTS:
      Overall, 2.2 per 1000 women (95% CI 1.9-2.5) experienced a complication, most
      commonly, heavy bleeding. Mifepristone abortion mortality is estimated to be 1.1
      per 100,000 based on one death (95% CI 0.3-5.9). CONCLUSIONS: The safety of
      mifepristone is high; few serious medical complications occur in routine clinical
      use.

PMID- 16102551
TI  - Cervical cancer screening continues to limit provision of contraception.
AB  - PURPOSE: Balancing needs for contraception and cervical cancer screening is
      challenging for clinicians. We assessed US obstetrician/gynecologists' practices
      regarding requirement of Pap testing before prescribing oral contraceptive or
      emergency contraceptive pills. METHODS: Questionnaires structured as clinical
      vignettes describing women desiring contraception with different risks of
      cervical dysplasia were mailed to a national sample of 355
      obstetrician/gynecologists. RESULTS: A minority (3%) of the 185
      obstetrician/gynecologists who responded would refill 12 months of oral
      contraceptives without requiring Pap testing. However, most would provide a
      limited supply of oral contraceptives until Pap testing could be performed. A
      substantial proportion (11-16%) would refuse to prescribe emergency contraception
      to women who they felt required Pap testing. Younger physicians, those practicing
      in academic settings and those who follow American Cancer Society guidelines were
      more willing to prescribe contraceptives without Pap testing. CONCLUSIONS:
      Cervical cancer screening continues to limit prescription of routine and
      emergency contraception by many US obstetrician/gynecologists.

PMID- 16102552
TI  - Emergency contraception: an intervention on primary care providers.
AB  - OBJECTIVE: We studied whether a single educational intervention can change
      provider knowledge, attitudes and practice patterns with respect to emergency
      contraception (EC). MATERIALS AND METHODS: Primary care providers completed a
      preintervention survey prior to attending a lecture on EC, and again 6 months
      later. There were 50 physicians, 4 advanced practice nurses and 2 physician
      assistants in the final sample (internal medicine 48%, family medicine 34%,
      obstetrics-gynecology 9%, and pediatrics/adolescent medicine 9%). RESULTS:
      Following the intervention, providers were more likely to agree that advance
      prescriptions should be given, disagree that the number of times EC is dispensed
      should be restricted and disagree that repeated EC use poses health risks. The
      proportion of providers who had ever given an advance prescription increased from
      18% to 41% (p = .007), and there was a trend toward a greater proportion of
      providers initiating counseling about EC from 36% to 54% (p = .057). CONCLUSIONS:
      A simple educational intervention was associated with a change in primary care
      provider attitudes and practice patterns regarding EC.

PMID- 16102553
TI  - Randomized assignment to copper IUD or depot-medroxyprogesterone acetate:
      feasibility of enrollment, continuation and disease ascertainment.
AB  - OBJECTIVES: We conducted a feasibility study to enroll and follow family planning
      acceptors who were randomly assigned to use an intrauterine device (IUD) or
      injectable depot-medroxyprogesterone acetate (DMPA). METHODS: Centers in Brazil,
      Guatemala, Egypt and Vietnam aimed to enroll 100 participants per site. Enrolled
      women were randomly assigned to have inserted a TCu 380A IUD, or to receive
      injections of 150 mg of DMPA every 3 months, and scheduled for up to 12 months of
      follow-up. We tested for cervical infection at first and final visits, and
      examined for signs of pelvic inflammatory disease (PID) at each visit. RESULTS:
      The sites screened 555 women and enrolled 368. Two women (0.5%) had three
      discomfort signs of PID during follow-up. The prevalence of gonorrhea at each
      woman's final follow-up visit was 0.5%, and the prevalence of chlamydia at final
      visit was 5.4%. Sixty-eight percent of women either completed 12 months of
      observation with their assigned method or were still using their method at the
      end of the study. CONCLUSION: A larger, definitive clinical trial appears
      feasible. The majority of women we approached agreed to participate; nearly 400
      women were enrolled; two thirds continued to use their assigned method until
      study closeout; and the STI risk was moderate.

PMID- 16102554
TI  - Transvaginal ultrasonographic assessment of the expulsion rate of intrauterine
      devices inserted in the immediate postpartum period: a pilot study.
AB  - OBJECTIVE: To compare the expulsion rates of intrauterine devices (IUDs) inserted
      in the immediate postpartum after vaginal birth and cesarean section. METHODS:
      Nineteen patients who had a vaginal birth and 19 patients who had a cesarean
      section at Hospital de Clinicas de Porto Alegre, Brazil, were selected for copper
      T 380A IUD insertion. With the aim of detecting clinically unnoticed dislodged
      devices, ultrasound examinations were performed at 1 month and between 3 and 12
      months after delivery. The IUDs were considered completely expelled when found
      outside the endometrial cavity (e.g., in the cervical canal) or outside the
      uterus (in the vagina). RESULTS: Expulsion rates were statistically different
      between the two groups: after a vaginal birth, 50% (ultrasound only) + 27.8%
      (clinical examination); and post-cesarean section, 0% (p < .001; OR 5.75, 95% CI
      2.36-14.01). CONCLUSION: Considering that the contraceptive efficacy of IUDs is
      associated with their intrauterine location, the high expulsion rates seen when
      they are inserted immediately after vaginal delivery contraindicate their use in
      this setting. The use of IUDs immediately after a cesarean section is still a
      reasonable alternative because its expulsion rate was zero. Ultrasound assessment
      of IUD positioning performed better than clinical examination, which failed to
      detect expulsion after postpartum insertion in 75% of the cases (9 from 12
      cases).

PMID- 16102555
TI  - In vivo assessment of NuvaRing placement.
AB  - NuvaRing, a combined contraceptive vaginal ring 54 mm in diameter, offers many
      advantages over oral contraceptives. To better delineate in vivo placement, we
      performed MRI to confirm its anatomical position. Two healthy users, one
      nulliparous and one parous, underwent a series of MRI: preinsertion, immediately
      postinsertion and after ambulation. Three-dimensional imaging of the human vagina
      demonstrates that in vivo, NuvaRing is located superior to the urogenital
      diaphragm (UGD), surrounding the cervix. The superior-most aspect of the ring
      lies behind (posterior) the cervix, at a level superior to the external os. The
      inferior aspect of the ring also lies in the vaginal canal above the UGD. The
      entire cervix rests inside the ring. The preambulation image in the nulliparous
      woman was the only exception. In this case, the upper portion of the ring was at
      the level of the lower-mid cervix and the lower aspect below the UGD. After
      ambulation, the ring moved cephalad and surrounded the cervix. In all instances,
      ambulation resulted in lower aspect of NuvaRing moving away from the introitus.
      In vivo, NuvaRing is compressed laterally forming a gentle oval in the anterior
      posterior direction (5-7 mm longer than wide), an effect that is seen more in
      nulliparous women.

PMID- 16102556
TI  - Attitudes of obstetrics and gynecology residents toward abortion participation: a
      Philadelphia area survey.
AB  - OBJECTIVE: The objective of this study was to evaluate the willingness of
      Philadelphia obstetrics and gynecology residents to participate in three abortion
      procedures for various fetal conditions. METHODS: Anonymous questionnaires were
      distributed to 310 residents from 18 programs. The survey asked the residents
      whether they would participate in first trimester dilatation and evacuation
      (D&E), second trimester prostaglandin induction or second trimester D&E for the
      following conditions: lethal fetal anomaly, nonlethal anomaly with certain long
      term functional consequences, possible long-term functional consequences, little
      or no long-term functional consequences and elective abortion of a normal fetus.
      RESULTS: Of the 148 respondents, the percentage of residents who would
      participate in a second trimester D&E for each fetal condition was significantly
      lower than that for a first trimester D&E (p < or = .001). Additionally, for each
      abortion procedure, the participation rates consistently fell for lesser degrees
      of fetal severity. Participation was significantly associated with preferences
      regarding abortion legislation and personal abortion stance. CONCLUSION: Resident
      attitudes regarding abortion participation were related to severity of the fetal
      condition, gestational age and procedure type.

PMID- 16102557
TI  - Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral
      density in women with hypothalamic amenorrhea and osteopenia: an open-label
      extension of a double-blind, placebo-controlled study.
AB  - OBJECTIVE: The effects of long-term triphasic oral contraceptive administration
      on bone mineral density (BMD) were investigated in premenopausal women with
      hypothalamic amenorrhea (HA) and osteopenia. METHODS: After completing three 28
      day cycles in the double-blind phase of a placebo-controlled trial, women (mean
      age, 26.7 years) who received norgestimate 180-250 microg/ethinyl estradiol 35
      microg (NGM/EE, n = 15) or placebo (n = 12) in the double-blind phase were to
      receive open-label NGM/EE for 10 additional cycles. RESULTS: For subjects
      completing > or =10 NGM/EE treatment cycles, mean posteroanterior total lumbar
      spine BMD (L1-L4) increased from 0.881+/-0.0624 g/cm2 at baseline (last visit
      prior to NGM/EE) to 0.894+/-0.0654 g/cm2 at final visit (p = .043); no
      significant changes in hip BMD occurred. Decreases in N-telopeptide, osteocalcin,
      procollagen type I propeptide and bone-specific alkaline phosphatase levels
      indicated effects on bone metabolism. CONCLUSIONS: Long-term administration of
      triphasic NGM/EE to osteopenic women with HA may increase total lumbar spine BMD.

PMID- 16102558
TI  - Effect of Norplant contraceptive on the bones of Nigerian women as assessed by
      quantitative ultrasound and serum markers of bone turnover.
AB  - Levonorgestrel is a commonly used progestin-only contraceptive that is available
      as subdermal (Norplant) and intrauterine implants. Other progestin-only
      contraceptives such as injectable medroxyprogeterone acetate have been shown to
      decrease bone mineral density in long-term users. We used calcaneal ultrasound to
      compare the bone quality of Nigerian women between 25 and 50 years of age who had
      Norplant implants for 1-4 years to that of women who were not using any form of
      hormonal contraceptive. The mean stiffness index of women who had Norplant
      implants for as long as 4 years was not significantly different from that of
      controls. However, serum markers of bone turnover were significantly decreased in
      women with Norplant implants compared to age-matched controls. Serum bone
      specific alkaline phosphatase was significantly decreased in subjects with
      Norplant implants for 1 year (13.7+/-6.0 vs. 23.0 U/L for controls, p = .001) and
      serum NTx was significantly decreased in subjects with implants for 3 years
      (10.6+/-4.9 vs. 17.6+/-7.7 bone collagen equivalents per liter for controls, p <
      .001). We conclude that although levonorgestrel contraceptive decreased overall
      bone turnover, it had no deleterious effect on the bone quality of women using
      Norplant implants for up to 4 years.

PMID- 16102559
TI  - Prevalence survey on condom use and infection of urogenital mycoplasmas in female
      sex workers in China.
AB  - GOAL: We evaluated the prevalence of condom use and the effects of condom use on
      urogenital mycoplasma infection in female sex workers in Jinjiang, China.
      METHODS: Two-hundred ninety-nine female sex workers from Jinjiang city, Jiangsu
      Province, were interviewed, and three mycoplasmas of Ureaplasma urealyticum (Uu),
      Mycoplasma hominis (Mh) and Mycoplasma genitalium (Mg) were detected by nested
      polymerase chain reaction in genital secretions of 72 female sex workers and 42
      female patients seen with symptoms of genital infection (control group). RESULTS:
      The results showed that 87.29% of the sex workers used condom in their last
      sexual intercourse, and that 2.68% did not use, 38.80% sometimes used and 58.52%
      used condoms every time in the last month. Those who were older, married and have
      a stable partnership used condoms less frequently. The infection rates of Uu, Mh
      and Mg were 77.78%, 34.72% and 16.67%, respectively, in sex worker subjects
      compared to those of controls at 59.52%, 9.62% and 21.43%, respectively. The
      infection rates of Uu and Mg were lower among all subjects (NS) who used condoms
      every time. In this observational study, genital mycoplasma infection was common
      and occurred more frequently among sex workers, and infection occurred less often
      when condoms were used. These results tend to support the efficacy of condom use
      in reducing urogenital mycoplasma infection among Chinese women.

PMID- 16102560
TI  - Corrosion behavior of Cu and the Cu-Zn-Al shape memory alloy in simulated uterine
      fluid.
AB  - Chemical immersion tests, electrochemical methods and atomic absorption
      spectrometry were employed to investigate the corrosion behavior of Cu and the Cu
      Zn-Al shape memory alloy (SMA) in simulated uterine fluid. The effect of pH on
      corrosion rate and corrosion potential was also investigated. The results
      indicated that in the static state in simulated uterine fluid,
      dealuminumification of the Cu-Zn-Al alloy occurred with Cl- combining with
      aluminum ions to form hydroxyl aluminum chloride. The hydroxyl aluminum chloride
      hydrolyzed readily and facilitated further dealuminumification corrosion. The
      corrosion process of Cu and Cu-Zn-Al SMA in simulated uterine fluid was
      controlled by cathodic reduction of oxygen. Because the tendency for surface
      ionization is greater for aluminum than for zinc, a compact protective aluminum
      layer was formed, which inhibited the cathodic reduction of oxygen. Hence, the
      corrosion rate of Cu-Zn-Al SMA was smaller than that of Cu in simulated uterine
      fluid. With increasing pH, the corrosion rate of Cu and Cu-Zn-Al SMA in simulated
      uterine fluid decreased and the open-circuit potential moved in a positive
      direction.

PMID- 16102561
TI  - The in vitro effect of emergency contraception doses of levonorgestrel on the
      acrosome reaction of human spermatozoa.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of three
      concentrations of levonorgestrel (LNG) comparable to the levels found in serum
      following ingestion of LNG as emergency contraception (EC) on the acrosome
      reaction (AR) of capacitated and noncapacitated spermatozoa of fertile men.
      MATERIALS AND METHODS: A total of 24 semen samples from three fertile men were
      evaluated. The spermatozoa were selected by Percoll gradient. Twelve samples were
      subsequently incubated with human tubal fluid medium supplemented with bovine
      serum albumin (HTF/BSA) for 20 h under capacitating conditions. The capacitated
      spermatozoa and the spermatozoa from the remaining 12 samples were exposed to LNG
      at 1, 10 and 100 ng/mL, to follicular fluid (FF) (20 %v/v) and to HTF medium. The
      ratio of live to dead spermatozoa was assessed after 1, 2 and 3 h of incubation
      at 37 degrees C and 5% CO2. After 30 min of exposure to the different LNG
      concentrations, aliquots were divided into two parts. In the first part,
      spermatozoa were immediately stained with Hoescht 33258 and fluorescein
      isothiocyanate-pisum sativum agglutinin (FITC-PSA) in order to assess AR rate and
      to repeat evaluation of the live-to-dead ratio. After 3 h of incubation, the
      remaining part of the aliquots were submitted to the same procedures. Each
      concentration of LNG was then compared with FF and HTF medium as positive and
      negative controls, respectively. RESULTS: The results showed that in vitro
      exposure to the three different LNG concentrations did not induce AR. CONCLUSION:
      This study failed to show any in vitro effect on AR of LNG concentrations similar
      to those found in serum following intake of LNG as EC. If this effect exists or
      if there is any other that influences sperm fertilizing capacity, in vitro
      experiments are probably not an appropriate way of testing it.

PMID- 16102563
TI  - Activation of ERK mitogen-activated protein kinase in human cells by the
      mycotoxin patulin.
AB  - Patulin (PAT), a mycotoxin produced by certain species of Penicillium and
      Aspergillus, is often detectable in moldy fruits and their derivative products.
      PAT led to a concentration-dependent and time-dependent increase in
      phosphorylation of extracellular signal-regulated protein kinases 1 and 2
      (ERK1/2) in human embryonic kidney (HEK293) cells, human peripheral blood
      mononuclear cells (PBMCs), and Madin-Darby canine kidney (MDCK) cells. Exposure
      of HEK293 cells to concentrations above 5 microM PAT for 30 min induced ERK1/2
      phosphorylation; activation of ERK1/2 was also observed after 24 h incubation
      with 0.05 microM of PAT. Treatment of human PBMCs for 30 min with 30 microM PAT
      dramatically increased the phosphorylated ERK1/2 levels. Both MEK1/2 inhibitors,
      U0126 and PD98059, suppressed ERK1/2 activation in either HEK293 or MDCK cells.
      In HEK293 cells, U0126-mediated inhibition of PAT-induced ERK1/2 phosphorylation
      resulted in a significant decrease in levels of DNA damage, expressed as tail
      moment values, in the single cell gel electrophoresis assay. Conversely, U0126
      did not affect cell viability, lactate dehydrogenase release, and the DNA
      synthesis rate in PAT-treated cultures. Exposure of HEK293 cells for 90 min to 15
      microM PAT elevated the levels of early growth response gene-1 (egr-1) mRNA, but
      not of c-fos, fosB, and junB mRNAs. These results indicate that in human cells,
      PAT causes a rapid and persistent activation of ERK1/2 and this signaling pathway
      plays an important role in mediating PAT-induced DNA damage and egr-1 gene
      expression.

PMID- 16102564
TI  - Chlorpyrifos exerts opposing effects on axonal and dendritic growth in primary
      neuronal cultures.
AB  - Evidence that children are widely exposed to organophosphorus pesticides (OPs)
      and that OPs cause developmental neurotoxicity in animal models raises
      significant concerns about the risks these compounds pose to the developing human
      nervous system. Critical to assessing this risk is identifying specific
      neurodevelopmental events targeted by OPs. Observations that OPs alter brain
      morphometry in developing rodents and inhibit neurite outgrowth in neural cell
      lines suggest that OPs perturb neuronal morphogenesis. However, an important
      question yet to be answered is whether the dysmorphogenic effect of OPs reflects
      perturbation of axonal or dendritic growth. We addressed this question by
      quantifying axonal and dendritic growth in primary cultures of embryonic rat
      sympathetic neurons derived from superior cervical ganglia (SCG) following in
      vitro exposure to chlorpyrifos (CPF) or its metabolites CPF-oxon (CPFO) and
      trichloropyridinol (TCP). Axon outgrowth was significantly inhibited by CPF or
      CPFO, but not TCP, at concentrations > or =0.001 microM or 0.001 nM,
      respectively. In contrast, all three compounds enhanced BMP-induced dendritic
      growth. Acetylcholinesterase was inhibited only by the highest concentrations of
      CPF (> or =1 microM) and CPFO (> or =1 nM); TCP had no effect on this parameter.
      In summary, these compounds perturb neuronal morphogenesis via opposing effects
      on axonal and dendritic growth, and both effects are independent of
      acetylcholinesterase inhibition. These findings have important implications for
      current risk assessment practices of using acetylcholinesterase inhibition as a
      biomarker of OP neurotoxicity and suggest that OPs may disrupt normal patterns of
      neuronal connectivity in the developing nervous system.

PMID- 16102565
TI  - Specific dose-dependent damage of Lieberkuhn crypts promoted by large doses of
      type 2 ribosome-inactivating protein nigrin b intravenous injection to mice.
AB  - Nigrin b is a non-toxic type 2 ribosome-inactivating protein as active as ricin
      at ribosomal level but 10(5) and 5 x 10(3) times less toxic for animal cell
      cultures and mice, respectively, than ricin. The purpose of the present study was
      to analyze the effects of intravenous injection of large amounts of nigrin b to
      the mouse. Injection through the tail vein of 16 mg/kg body weight killed all
      mice studied before 2 days. Analysis of several major tissues by light microscopy
      did not reveal gross nigrin b-promoted changes, except in the intestines which
      appeared highly damaged. As a consequence of the injury, the villi and crypt
      structures of the small intestine disappeared, leading to profuse bleeding and
      death. In contrast, intravenous injection of 5 mg/kg body weight was not lethal
      to mice but did trigger reversible toxic effects. In both cases, lethal and sub
      lethal doses, the target of nigrin b appeared to be the highly proliferating stem
      cells of the intestinal crypts, which had undergone apoptotic changes. In
      contrast to nigrin b, the injection of 3 mug/kg of ricin kills all mice in 5 days
      but does not trigger apoptosis in the crypts. Therefore, the effect seen with sub
      lethal nigrin b concentrations seems to be specific. Nigrin b killed COLO 320
      human colon adenocarcinoma cells with an IC(50) of 3.1 x 10(-8) M and the effect
      was parallel to the extent of DNA fragmentation of these cells. Accordingly,
      despite the low general toxicity exerted by nigrin b as compared with ricin,
      intravenous injection of large amounts of nigrin b is able to kill mouse
      intestinal stem cells without threatening the lives of the animals, thereby
      opening a door for its use for the targeting of intestinal stem cells.

PMID- 16102566
TI  - Metabolism and toxicity of arsenic in human urothelial cells expressing rat
      arsenic (+3 oxidation state)-methyltransferase.
AB  - The enzymatic methylation of inorganic As (iAs) is catalyzed by As(+3 oxidation
      state)-methyltransferase (AS3MT). AS3MT is expressed in rat liver and in human
      hepatocytes. However, AS3MT is not expressed in UROtsa, human urothelial cells
      that do not methylate iAs. Thus, UROtsa cells are an ideal null background in
      which the role of iAs methylation in modulation of toxic and cancer-promoting
      effects of this metalloid can be examined. A retroviral gene delivery system was
      used in this study to create a clonal UROtsa cell line (UROtsa/F35) that
      expresses rat AS3MT. Here, we characterize the metabolism and cytotoxicity of
      arsenite (iAs(III)) and methylated trivalent arsenicals in parental cells and
      clonal cells expressing AS3MT. In contrast to parental cells, UROtsa/F35 cells
      effectively methylated iAs(III), yielding methylarsenic (MAs) and dimethylarsenic
      (DMAs) containing either As(III) or As(V). When exposed to MAs(III), UROtsa/F35
      cells produced DMAs(III) and DMAs(V). MAs(III) and DMAs(III) were more cytotoxic
      than iAs(III) in UROtsa and UROtsa/F35 cells. The greater cytotoxicity of
      MAs(III) or DMAs(III) than of iAs(III) was associated with greater cellular
      uptake and retention of each methylated trivalent arsenical. Notably, UROtsa/F35
      cells were more sensitive than parental cells to the cytotoxic effects of
      iAs(III) but were more resistant to cytotoxicity of MAs(III). The increased
      sensitivity of UROtsa/F35 cells to iAs(III) was associated with inhibition of
      DMAs production and intracellular accumulation of MAs. The resistance of
      UROtsa/F35 cells to moderate concentrations of MAs(III) was linked to its rapid
      conversion to DMAs and efflux of DMAs. However, concentrations of MAs(III) that
      inhibited DMAs production by UROtsa/F35 cells were equally toxic for parental and
      clonal cell lines. Thus, the production and accumulation of MAs(III) is a key
      factor contributing to the toxicity of acute iAs exposures in methylating cells.

PMID- 16102567
TI  - Anti-diabetic action of Punica granatum flower extract: activation of PPAR-gamma
      and identification of an active component.
AB  - Peroxisome proliferator-activated receptor (PPAR)-gamma activators are widely
      used in the treatment of type 2 diabetes because they improve the sensitivity of
      insulin receptors. Punica granatum flower (PGF) has been used as an anti-diabetic
      medicine in Unani medicinal literature. The mechanism of actions is, however,
      unknown. In the current study, we demonstrated that 6-week oral administration of
      methanol extract from PGF (500 mg/kg, daily) inhibited glucose loading-induced
      increase of plasma glucose levels in Zucker diabetic fatty rats (ZDF), a genetic
      animal model for type 2 diabetes, whereas it did not inhibit the increase in
      Zucker lean rats (ZL). The treatment did not lower the plasma glucose levels in
      fasted ZDF and ZL rats. Furthermore, RT-PCR results demonstrated that the PGF
      extract treatment in ZDF rats enhanced cardiac PPAR-gamma mRNA expression and
      restored the down-regulated cardiac glucose transporter (GLUT)-4 (the insulin
      dependent isoform of GLUTs) mRNA. These results suggest that the anti-diabetic
      activity of PGF extract may result from improved sensitivity of the insulin
      receptor. From the in vitro studies, we demonstrated that the PGF extract
      enhanced PPAR-gamma mRNA and protein expression and increased PPAR-gamma
      dependent mRNA expression and activity of lipoprotein lipase in human THP-1
      differentiated macrophage cells. Phytochemical investigation demonstrated that
      gallic acid in PGF extract is mostly responsible for this activity. Thus, our
      findings indicate that PPAR-gamma is a molecular target for PGF extract and its
      prominent component gallic acid, and provide a better understanding of the
      potential mechanism of the anti-diabetic action of PGF.

PMID- 16102568
TI  - Plant lectins as carriers for oral drugs: is wheat germ agglutinin a suitable
      candidate?
AB  - Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars
      expressed also by gastrointestinal epithelial cells. WGA is currently
      investigated as an anti-tumor drug and as a carrier for oral drugs. Information
      on whether it can cross the gastrointestinal epithelium and on its possible
      effects on the integrity of the epithelial layer is however scanty or lacking,
      and herein we address these issues. Differentiated Caco2 cells have been used as
      a model of polarized intestinal epithelium. WGA concentration at both the apical
      and the basolateral side of the epithelium has been quantified using a sensitive
      ELISA assay (sensitivity threshold 0.84 nM). Trans epithelial electrical
      resistance (TEER) has been measured to evaluate the integrity of the epithelium
      upon treatments with WGA. (3)H-Mannitol (182.2 Da) and FITC-dextran (3000 Da)
      have been used to measure the permeability of the epithelium. Cell viability has
      been measured by the MTT, by 7-AAD uptake, and Annexin-V binding assays. Up to a
      concentration of 5.6 microM, approximately 0.1% of intact WGA molecules only
      could cross the epithelial layer. WGA perturbed the integrity of the epithelium
      and increased the permeability of the tissue in a dose- and time-dependent
      manner. WGA did not induce cell death but increased the permeability of
      individual cells to 7-AAD which is normally not uptaken by viable cells. These
      data allowed us to define a toxicity threshold for WGA on epithelial cells. WGA
      suitability as a carrier for oral drugs can therefore be evaluated on a rational
      basis.

PMID- 16102569
TI  - Cadmium and renal cancer.
AB  - BACKGROUND: Rates of renal cancer have increased steadily during the past two
      decades, and these increases are not explicable solely by advances in imaging
      modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that
      accumulates in the kidney cortex and is a cause of end-stage renal disease.
      Several observations suggest that cadmium may be a cause of renal cancer.
      METHODS: We performed a systematic review of the literature on cadmium and renal
      cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological
      and eleven clinical studies. RESULTS: Despite different methodologies, three
      large epidemiologic studies indicate that occupational exposure to cadmium is
      associated with increased risk renal cancer, with odds ratios varying from 1.2 to
      5.0. Six of seven studies that compared the cadmium content of kidneys from
      patients with kidney cancer to that of patients without kidney cancer found lower
      concentrations of cadmium in renal cancer tissues. CONCLUSIONS: Exposure to
      cadmium appears to be associated with renal cancer, although this conclusion is
      tempered by the inability of studies to assess cumulative cadmium exposure from
      all sources including smoking and diet. The paradoxical findings of lower cadmium
      content in kidney tissues from patients with renal cancer may be caused by
      dilution of cadmium in rapidly dividing cells. This and other methodological
      problems limit the interpretation of studies of cadmium in clinical samples.
      Whether cadmium is a cause of renal cancer may be answered more definitively by
      future studies that employ biomarkers of cadmium exposure, such as cadmium levels
      in blood and urine.

PMID- 16102570
TI  - Role of the LAT adaptor in T-cell development and Th2 differentiation.
AB  - LAT (linker for activation of T cells) is an integral membrane adaptor protein
      that constitutes in T cells a major substrate of the ZAP-70 protein tyrosine
      kinase. LAT coordinates the assembly of a multiprotein signaling complex through
      phosphotyrosine-based motifs present within its intracytoplasmic segment. The
      resulting "LAT signalosome" links the TCR to the main intracellular signalling
      pathways that regulate T-cell development and T-cell function. Early studies
      using transformed T-cell lines suggested that LAT acts primarily as a positive
      regulator of T-cell receptor (TCR) signalling. The partial or complete inhibition
      of T-cell development observed in several mouse lines harboring mutant forms of
      LAT was congruent with that view. More recently, LAT "knock-ins" harboring point
      mutations in the four COOH-terminal tyrosine residues, were found to develop
      lymphoproliferative disorders involving polyclonal T cells that produced high
      amounts of T helper-type 2 (Th2) cytokines. This unexpected finding revealed that
      LAT also constitutes a negative regulator of TCR signalling and T-cell
      homeostasis. Although LAT is also expressed in mast cells, natural killer cells,
      megakaryocytes, platelets, and early B cells, the present review specifically
      illustrates the role LAT plays in the development and function of mouse T cells.
      As discussed, the available data underscore that a novel immunopathology proper
      to defective LAT signalosome is taking shape.

PMID- 16102571
TI  - The integration of conventional and unconventional T cells that characterizes
      cell-mediated responses.
AB  - This review builds on evidence that cell-mediated immune responses to bacteria,
      viruses, parasites, and tumors are an integration of conventional and
      unconventional T-cell activities. Whereas conventional T cells provide clonal
      antigen-specific responses, unconventional T cells profoundly regulate
      conventional T cells, often suppressing their activities such that
      immunopathology is limited. By extrapolation, immunopathologies and inflammatory
      diseases may reflect defects in regulation by unconventional T cells. To explore
      the function of unconventional T cells, several extensive gene expression
      analyses have been undertaken. These studies are reviewed in some detail, with
      emphasis on the mechanisms by which unconventional T cells may exert their
      regulatory functions. Highlighting the fundamental nature of T-cell integration,
      we also review emerging data that the development of conventional and
      unconventional T cells is also highly integrated.

PMID- 16102572
TI  - Negative regulation of cytokine and TLR signalings by SOCS and others.

PMID- 16102573
TI  - Pathogenic T-cell clones in autoimmune diabetes: more lessons from the NOD mouse.
AB  - T-cell clones that can efficiently transfer diabetes to prediabetic nonobese
      diabetic (NOD) mice provide a powerful approach to dissecting the autoimmune
      disease process and for investigating immunoregulation. Diabetogenic T-cell
      clones carried in culture allow for detailed analysis of T-cell effector function
      and in vivo activity, and thus the contribution of a single clonotype to
      pathogenesis can be studied. As T cells comprising most or all of the repertoire
      in T-cell receptor transgenic (TCR-Tg) mice, diabetogenic T-cell clones have led
      to new variations on the NOD mouse model of autoimmune disease. T-cell clones are
      being used to screen peptide libraries and proteomic arrays to identify the
      autoantigens that drive these clones in vivo and to extend our knowledge of the
      processes that give rise to these antigens. With the identification of peptide
      agonists and natural ligands, the development of MHC-peptide multimers has been
      possible. These reagents can track T cells in vivo and thus provide new
      approaches for disease diagnosis and therapy as well as a versatile set of tools
      for basic research on how T cells contribute to autoimmune disease.

PMID- 16102575
TI  - New insights into alternative mechanisms of immune receptor diversification.
AB  - The clonal commitment, selection, and expansion of B and T lymphocytes expressing
      diversified receptors provide the underlying basis for the jawed vertebrates
      adaptive immune response. At the core of this process is the rearrangement and
      somatic modification of segmental genetic elements that encode the constituent
      components of immunoglobulins and T-cell antigen receptors. No evidence has been
      found for a similar mechanism outside of jawed vertebrates; however,
      invertebrates and jawless vertebrates are subjected to continuous exposure to
      pathogenic bacteria, viruses, and parasites. The invertebrates and jawless
      vertebrates as well as jawed vertebrates all encode a variety of mediators of
      innate immunity. Several reports of extensive germline diversification of
      conventional innate receptors, as well as molecules that resemble innate
      receptors but undergo germline and somatic modification, have been made recently.
      The range of such molecules, which include the fibrinogen-related proteins
      (FREPs) in a mollusc, variable region-containing chitin-binding proteins (VCBPs)
      in a cephalochordate, variable lymphocyte receptors (VLRs) in jawless
      vertebrates, and novel immune-type receptors (NITRs) in bony fish, encompasses
      both the immunoglobulin gene superfamily (IgSF) and leucine-rich repeat (LRR)
      proteins. Although these molecules vary markedly in form and likely in function,
      growing evidence suggests that they participate in various types of host defense
      and thereby represent significant alternatives to current paradigms of innate and
      adaptive immune receptors. Unusual genetic mechanisms for diversifying
      recognition proteins may be a widespread characteristic of animal immunity.

PMID- 16102574
TI  - The biology of human lymphoid malignancies revealed by gene expression profiling.
AB  - Gene expression profiling provides a quantitative molecular framework for the
      study of human lymphomas. This genomic technology has revealed that existing
      diagnostic categories are comprised of multiple molecularly and clinically
      distinct diseases. Diffuse large B-cell lymphoma (DLBCL), for example, consists
      of three gene expression subgroups, termed germinal center B-cell-like (GCB)
      DLBCL, activated B-cell-like (ABC) DLBCL, and primary mediastinal B-cell lymphoma
      (PMBL). These DLBCL subgroups arise from different stages of normal B-cell
      differentiation, utilize distinct oncogenic mechanisms, and differ in their
      ability to be cured by chemotherapy. Key regulatory factors and their target
      genes are differentially expressed among these subgroups, including BCL-6, Blimp
      1, and XBP1. ABC DLBCL and PMBL depend upon constitutive activation of the NF
      kappaB pathway for their survival but GCB DLBCL does not, demonstrating that this
      pathway is a potential therapeutic target for certain DLBCL subgroups. In DLBCL,
      mantle cell lymphoma, and follicular lymphoma, gene expression profiling has also
      been used to create gene expression-based models of survival, which have
      identified the biological characteristics of the tumors that influence their
      clinical behavior. In mantle cell lymphoma, the length of survival following
      diagnosis is primarily influenced by the tumor proliferation rate, which can be
      quantitatively measured by a proliferation gene expression "signature." Based on
      this accurate measure, the proliferation rate can now be viewed as an integration
      of several oncogenic lesions that each increase progression from the G1 to the S
      phase of the cell cycle. In DLBCL and follicular lymphoma, gene expression
      profiling has revealed that the molecular characteristics of non-malignant tumor
      infiltrating immune cells have a major influence on the length of survival. The
      implications of these insights for the diagnosis and treatment of non-Hodgkin
      lymphomas are discussed.

PMID- 16102576
TI  - The repair of DNA damages/modifications during the maturation of the immune
      system: lessons from human primary immunodeficiency disorders and animal models.
AB  - The immune system is the site of various genotoxic stresses that occur during its
      maturation as well as during immune responses. These DNA lesions/modifications
      are primarily the consequences of specific physiological processes such as the
      V(D)J recombination, the immunoglobulin class switch recombination (CSR), and the
      generation of somatic hypermutations (SHMs) within Ig variable domains. The DNA
      lesions can be introduced either by specific factors (RAG1 and RAG2 in the case
      of V(D)J recombination and AID in the case of CSR and SHM) or during the various
      phases of cellular proliferation and cellular activation. All these DNA lesions
      are taken care of by the diverse DNA repair machineries of the cell. Several
      animal models as well as human conditions have established the critical
      importance of these DNA lesions/modifications and their repair in the physiology
      of the immune system. Indeed their defects have consequences ranging from immune
      deficiency to development of immune malignancy. The survey of human pathology has
      been highly instrumental in the past in identifying key factors involved in the
      generation of DNA modifications (AID for the Ig CSR and generation of SHM) or the
      repair of specific DNA damages (Artemis for V(D)J recombination). Defects in
      factors involved in the cell cycle checkpoints following DNA damage also have
      deleterious consequences on the immune system. The continuous survey of human
      diseases characterized by primary immunodeficiency associated with increased
      sensitivity to ionizing radiation should help identify other important DNA repair
      factors essential for the development and maintenance of the immune system.

PMID- 16102577
TI  - Antibody class switch recombination: roles for switch sequences and mismatch
      repair proteins.
AB  - Mechanisms and targeting of antibody class switch DNA recombination are reviewed.
      Particular emphasis is on the roles for the DNA sequences comprising switch (S)
      regions, including the S-region tandem repeats, and on the roles of proteins that
      are involved in both DNA mismatch repair and in class switch recombination.

PMID- 16102578
TI  - Identification of inactivating mutations in the JAK1, SYNJ2, and CLPTM1 genes in
      prostate cancer cells using inhibition of nonsense-mediated decay and microarray
      analysis.
AB  - We have developed a simple analytical method that increases the efficiency of
      identifying mutant genes in cell lines after the inhibition of nonsense-mediated
      decay (NMD). The approach assumes that the spectra of mutant genes differ between
      cell lines of the same tumor origin. Thus, by analyzing more than one cell line
      in parallel and taking into account not only changes in mRNA levels after the
      inhibition of NMD, but also comparing mRNA levels between cell lines before the
      inhibition of NMD, the vast majority of false positives were eliminated from the
      analysis. In this study, we used Affymetrix oligonucleotide arrays to compare
      mRNA profiles of two prostate cancer cell lines, PC3 and LNCaP, before and after
      emetine treatment. As a result of our modified approach, from the 14,500 genes
      present on the array, 7 were identified as candidates from LNCaP cells and 1 was
      identified from PC3 cells. Sequence analysis of five of these candidate genes
      identified gene-inactivating mutations in four of them. Homozygous mutations were
      found in the synaptojanin 2 (SYNJ2) and the cleft lip and palate CLPTM1 genes.
      Two different heterozygous mutations in the Janus kinase 1 (JAK1) gene result in
      complete loss of the protein in several different prostate cancer cell lines.

PMID- 16102579
TI  - Chromosomal aberrations in cell lines derived from thyroid tumors spontaneously
      developed in TRbetaPV/PV mice.
AB  - The etiology and genetic alterations of follicular thyroid carcinoma are not well
      understood. By targeting a mutation (PV) into the thyroid hormone receptor beta
      gene (TRbetaPV mouse), we created a knock-in mutant TRbeta(PV/PV) mouse that
      spontaneously develop follicular thyroid carcinoma with progression to metastasis
      similar to human follicular thyroid carcinoma. This mouse model provides a
      valuable tool to ascertain the nature and the extent of genomic rearrangements
      that occur during carcinogenesis of the thyroid. Spectral karyotyping analysis
      (SKY) of seven cell lines derived from thyroid tumors developed in TRbeta(PV/PV)
      mice showed that all of them had abnormal karyotypes, with chromosome number
      ranging from near-diploid (39-42 chromosomes) to hypotetraploid (63-79
      chromosomes). These seven cell lines also exhibited a variety of structural
      chromosomal aberrations, including common recurrent translocations and deletions.
      This SKY analysis shows that the development and progression of follicular
      thyroid carcinoma in knock-in TRbeta(PV/PV) mutant mice comprise recurrent
      structural and numerical genomic changes, some of which mimic those described in
      human thyroid cancer.

PMID- 16102580
TI  - Screening by fluorescence in situ hybridization for MLL status at diagnosis in
      239 unselected patients with acute myeloblastic leukemia.
AB  - A large number of abnormalities involving the MLL gene have been associated with
      hematological malignancies, including acute myeloblastic leukemias (AML). Given
      the overall unfavorable prognosis of AML with an MLL abnormality, its reliable
      and accurate detection is needed for informed treatment decision. We therefore
      investigated the occurrence of MLL abnormalities in 239 unselected consecutive
      AML patients, using conventional cytogenetic and fluorescent in situ
      hybridization (FISH) analyses. FISH analysis for MLL was performed using a
      commercial dual-color probe. Of the 239 patients, 30 (12.6%) showed MLL
      abnormalities under FISH analysis, 10 (4.2%) showed a split signal indicating the
      disruption of the MLL gene by translocation or insertion, and 20 (8.4%) showed
      overrepresentation of the MLL gene without evidence of rearrangement. MLL
      abnormalities were more frequently found in AML-M5 and M4, mainly as
      rearrangements, and in AML-M2, mainly as overrepresentation. Our results are in
      agreement with those reported in other studies. All M2, M4, and M5 AML patients
      without known recurrent translocations, such as t(8;21) and inv(16), should be
      investigated by FISH with an MLL probe because it allows the detection of MLL
      rearrangement that would go undetected by conventional cytogenetics and because
      it has the ability of detecting multiple copies of the MLL gene in, for example,
      marker chromosomes and double minutes.

PMID- 16102581
TI  - High incidence and intraclonal heterogeneity of chromosome 11 aberrations in
      patients with newly diagnosed multiple myeloma detected by multiprobe interphase
      FISH.
AB  - In multiple myeloma, additional copies of chromosome 11 material, reported to
      confer an unfavorable prognosis, have been found in 20-45% of patients. To assess
      the incidence and extent of chromosome 11 aberrations, we performed interphase
      fluorescence in situ hybridization on CD138+ bone marrow plasma cells of 50 newly
      diagnosed myeloma patients, using seven locus-specific probes for chromosome 11,
      one for 13q14.3, and a probe set for translocation t(11;14). In 33 of 50
      patients, chromosome 11 aberrations were found. Results indicated a marked
      intraclonal heterogeneity: in 13 patients, trisomy 11; in 10 patients, subclones
      with trisomy 11 and partial trisomies 11q coexisted; in 6 patients, only a
      partial trisomy 11q; and in 6 patients, a tetrasomy or partial tetrasomy 11. The
      coexistence of subclones with varying extent and copy numbers of chromosome 11
      material indicates ongoing structural changes and clonal evolution. Hybridization
      results delineated 11q23 and 11q25 as the most frequently gained regions, which
      supports a relevant pathogenetic role of genes on 11q23 and 11q25. To confirm the
      high incidence of 11q23 gains, a further 50 patients (total n=100) were analyzed
      for 11q23 and 13q14.3. Myeloma with gains of 11q23 showed a low frequency of
      deletion 13q14.3 and may prove to be a distinct subgroup of this disease.

PMID- 16102582
TI  - Recurrent duplication of Xq27-qter in hematological malignancies revealed by
      multicolor fluorescence in situ hybridization and multicolor banding.
AB  - Multicolor fluorescence in situ hybridization (M-FISH) experiments were performed
      to determine the composition of abnormal complex karyotypes in 15 cases of
      hematological malignancy. Four cases were found to have unsuspected unbalanced X
      chromosome translocations, which resulted in the presence of extra X chromosome
      material. We determined the identity of the duplicated chromosome regions using
      the multicolor banding (mBAND) technique. Xq27-qter was duplicated in three of
      the four male cases with an X chromosome abnormality (i.e., in one third of male
      cases and one fifth of all cases). These preliminary results may point to the
      existence of a recurrent chromosome abnormality, either translocation at a
      specific Xq27 locus or duplication of Xq27-qter.

PMID- 16102583
TI  - Cytogenetic findings, Trp53 mutations, and hormone responsiveness in a
      medroxyprogesterone acetate induced murine breast cancer model.
AB  - Medroxyprogesterone acetate (MPA)-induced mammary carcinomas express high levels
      of estrogen (ER) and progesterone receptors (PR) and when transplanted in
      syngeneic mice they show a progestin-dependent (PD) growth pattern. By successive
      transplantation, progestin-independent (PI) variants were generated and showed a
      different response to antihormone therapy. A diploid chromosome number (2n=40)
      was found in three of five PD tumors, with numbers in the triploid to tetraploid
      range in the other two. Some PI tumors were diploid, but most were aneuploid (8
      of 12 tumors). The most frequent alterations found in PD and PI tumors were gains
      of chromosomes 3, 4, and 6 and losses of chromosomes 16 and X. Chromosomes 4 and
      7 were involved in translocations in three of the four tumor families studied.
      single-strand conformation polymorphism analysis revealed a point mutation on the
      Trp53 gene in one of the PD tumors; this showed a stable diploid karyotype,
      suggesting that mutated Trp53 is not uniquely involved in chromosome instability.
      We have shown that hormone independence may be acquired without changes in
      ploidy, suggesting that the increase in ploidy is favored by successive
      transplantation. In our model, diploid tumors responded to hormone treatment but
      aneuploid tumors were either responsive or not.

PMID- 16102584
TI  - Identification of oligodendroglioma specific chromosomal copy number changes in
      the glioblastoma MI-4 cell line by array-CGH and FISH analyses.
AB  - Glioblastomas, the most frequent and malignant glial tumors, are known to be
      phenotypically heterogeneous. A low fraction of glioblastomas is associated with
      specific chromosomal losses at 1p and 19q, which are commonly found in
      oligodendrogliomas and are generally considered to be a primary event in the
      development of these tumors. Subsequent progression of oligodendroglial tumors
      appears to be triggered by additional molecular features underlying the
      transition to anaplastic oligodendroglioma and glioblastoma multiforme (GBM) such
      as deletions of 9p and 10q, and alterations of CDKN2A (p16), which is located at
      9p21. These findings strengthen the view that GBM on rare occasions may develop
      from oligodendroglial differentiated cells. In the present study, we evaluated
      the newly established MI-4 glioblastoma cell line, which displays 1p and 19q
      specific alterations targeting preferential regions of allelic loss in glial
      neoplasms, by array-CGH and fluorescence in situ hybridization (FISH) analyses
      that were combined to obtain a high resolution map of targeted chromosome
      rearrangements and copy number changes throughout the genome. Genome-wide and
      chromosome 19 full coverage array-CGH analysis of the MI-4 cell line revealed
      that in this particular cell line, 1p-specific loss, including the CDKN2 (p18)
      gene, is not accompanied by loss of the previously described 19q13.3 tumor
      suppressor candidate region. Interestingly, the array-CGH (CGHa) profile showed
      an increase in copy number along most of 19q including the AKT2 oncogene and the
      KLKs gene family, which have previously been shown to be amplified in pancreatic
      carcinomas and upregulated in several tumors, respectively. The concomitant 1p
      partial loss and chromosome 19 alterations, with the +7 and -10-specific GBM
      markers associated with homozygous deletion of 9p21.3 including CDKN2A (p16), are
      distinct features of the glioblastoma MI-4 cell line, illustrating its origin
      from an olidodendroglial tumor. Based on these results, we conclude that the MI-4
      glioblastoma cell line might function as a model system for investigations into
      the behavior of a defined oligodendroglioma subtype.

PMID- 16102585
TI  - Loss of 10p material in a child with human papillomavirus-positive disseminated
      bilateral retinoblastoma.
AB  - Retinoblastoma (RB) is a malignant childhood tumor that results from loss or
      inactivation of both alleles of the RB1 gene. Human papillomavirus (HPV) DNA
      sequences have been found in RB tissue, suggesting a role of the viral infection
      with RB. We here describe a child with disseminated bilateral RB without familial
      history, who displayed a loss of material from 10p. Fluorescence in situ
      hybridization studies showed a somatic loss of both alleles of the RB1 gene.
      Moreover, sequences for HPV-6a were detected on DNA extracted from eye tumor
      tissue and from nonstimulated peripheral blood leukocyte cultures. The eye tumor
      tissue was also positive for HPV L1 viral proteins. Repeated loss of the short
      arm of chromosome 10 in HPV-transfected keratinocytes has been reported. Loss of
      heterozygosity in 10p14 approximately p15 is also frequent in cervical cancers.
      Therefore, it seems probable that the abnormalities on 10p detected in the
      present case are related to the HPV infection. Thus, HPV could be a cofactor in
      the progression of RB by promoting nonrandom additional mutations.

PMID- 16102586
TI  - THY-1 induction is associated with up-regulation of fibronectin and
      thrombospondin-1 in human ovarian cancer.
AB  - We recently identified THY-1 as a putative tumor suppressor gene for human
      ovarian cancer. To understand the carcinogenic role of THY-1, and its downstream
      effects on cancer cells, a THY-1 inducible system was established in the human
      ovarian cancer cell line SKOV-3 based on the tetracycline (tet) regulating
      system. To establish an inducible system for Thy-1 expression, two plasmids,
      pUHD172-1neo and pTEP4mThy-1, which are neomycin and hygromycin resistant were co
      transfected into the ovarian carcinoma cell line, SKOV-3. The inducibility of Thy
      1 expression in the SKOV-3 cell line by doxycycline (dox) was determined by
      northern blot analysis, immunocytochemistry, and flow cytometry. A time course
      study revealed that Thy-1 expression is induced 3 hours post dox exposure.
      Expression was reversible such that 12 hours post the removal of dox almost no
      Thy-1 could be detected. Furthermore, 2 genes, Fibronectin (FN) and
      Thrombospondin (TSP-1) involved in cellular differentiation and the regulation of
      tumor angiogenesis, respectively, were found to be up-regulated upon THY-1
      induction. In contrast, the gene SPARC was found to be independent of Thy-1
      expression. This study supports the hypothesis that THY-1 plays a critical role
      in regulating downstream genes associated with the regulation of ovarian tumor
      growth and cellular differentiation.

PMID- 16102587
TI  - Jumping translocations in multiple myeloma.
AB  - Jumping translocations (JT) have been defined as nonreciprocal translocations
      involving a same donor chromosome arm or chromosome segment onto two or more
      recipient chromosomes in different cell lines in the same patient, leading to a
      mosaic karyotype. This definition has been expanded to also include extra copies
      of a same donor segment on different recipient chromosomes in a single clone. Six
      patients with multiple myeloma and JT involving chromosome arm 1q were identified
      among 37 patients presenting with chromosome 1 abnormalities. All six patients
      had an advanced disease and a short survival. The literature review allowed us to
      identify 24 additional patients with JT. Chromosomes 16 and 19 were the
      recipients in 11 (45.8%) and 6 (25%) of these 24 patients, respectively.
      Breakpoints on the recipient chromosomes were pericentromeric in 46.2% and
      telomeric in 40.4% of the breakpoints recorded. Since telomeres are made of
      (TTAGGG)n tandem DNA repeats that are also found in the pericentromeric
      heterochromatic regions (interstital telomeric sequences), it is presumed that
      jumping translocations arise through illegimate recombination between telomere
      repeat sequences and interstitial telomeric sequences.

PMID- 16102588
TI  - Genotype stability and clonal evolution of hepatocellular carcinoma assessed by
      autopsy-based genome-wide microsatellite analysis.
AB  - It is widely accepted that chromosomal instability is an essential feature of
      cancer cells including hepatocellular carcinoma (HCC) cells. For an accurate
      characterization of clonal evolution of HCC cells, we studied chromosomal
      alterations in various metastatic lesions in an autopsy case of HCC. Tissues from
      the main tumor, which consisted of 2 macroscopically distinct portions, and from
      intrahepatic metastasis, portal vein thrombus, epiploic lymph node metastasis,
      and pulmonary metastasis as well as from the non-tumorous liver were analyzed
      with comprehensive microsatellite analysis. Alleles showing imbalance of the main
      tumor were further subjected to comparative duplex PCR, with use of a retained
      allele as an internal control, to determine whether the imbalance was the result
      of chromosomal gain or loss. A striking finding was that allelic imbalances
      detected in the main tumor and metastatic lesions were almost identical, showing 
      1p, +1q, -4q, -7, -8p, +8q, +9q, +10, -13q, -17p, +19p, -19q, and -X. Additional
      alterations of +2q and -16q were detected in one portion of the main tumor and
      the portal vein thrombus. In conclusion, clonal evolution of the HCC cells during
      metastatic progression seems rare, in contrast to many recurrent chromosomal
      aberrations that may have accumulated before the clinical manifestation.

PMID- 16102589
TI  - Ovarian cancer is a heterogeneous disease.
AB  - The purpose of this study was to systematically evaluate the molecular profiles
      of different histologic types of epithelial ovarian cancer before the disease has
      metastasized beyond the ovary. Stage 1 epithelial ovarian cancers were chosen for
      analysis of early genetic events associated with different cell types.
      Allelotyping of 47 cases was performed using 224 polymorphic markers. Analysis
      with Fisher's exact test found markers specific for grade 3 tumors and clear cell
      histology. Hierarchal clustering analysis using dChip software revealed that the
      pattern of allele loss in eight regions on four chromosomes led to grouping of
      grade 3 tumors, endometrioid (grades 1 and 2) tumors, and clear cell tumors. We
      conclude that ovarian cancer is a heterogeneous disease in which histologic
      phenotypes correlate with distinct genetic patterns.

PMID- 16102590
TI  - Live cell catapulting and recultivation does not change the karyotype of HCT116
      tumor cells.
AB  - We used laser microdissection and pressure catapulting (LMPC) to isolate and
      subsequently recultivate cells from the colorectal cancer cell line HCT116. Cell
      isolation and recultivation was repeated 5 times from the preceding cell culture.
      The chromosomal composition of the HCT116 cells was analyzed at the beginning and
      after each recultivation. We did not observe any additional chromosomal
      structural or copy number changes during this procedure. Our data suggest that
      the procedure of cell isolation by LMPC and subsequent recultivation does not
      affect the karyotype of the respective cells. This technology will facilitate the
      analysis of different cell populations in a heterogeneous tumor cell population.

PMID- 16102591
TI  - Karyotypic characterization of 64 nonmalignant thyroid goiters.
AB  - Cytogenetic analyses were performed on 64 nonmalignant thyroid goiters (11 common
      and 53 multinodular goiters) after short-term culture. The majority of goiters
      (67%) were characterized by a normal karyotype, but in 5 common (45%) and 16
      nodular (30%) goiters, small clones with various numerical and/or structural
      aberrations were found, in addition to many normal cells. Trisomy or tetrasomy 7
      was the most frequent numerical aberration, seen in five cases. Deletion of 18p11
      was found in four cases, and in three of them as the sole change. Selection and
      clonal evolution of aneuploid cells present in nonmalignant goiters could
      underlie progression into adenoma formation.

PMID- 16102592
TI  - Biallelic deletion and loss of expression analysis of genes at FRA2G common
      fragile site in tumor-derived cell lines.
AB  - Common fragile sites (CFS) are regions of chromosome instability that show gaps
      or breaks when cells are exposed to particular culture condition. Much evidence
      suggests that CFSs are causally related to cancer as breakpoints in recurrent
      chromosome mutations and as sites of viral integration. We investigated the FRA2G
      CFS (2q31) for biallelic deletions and loss of expression in a panel of 19 tumor
      derived cell lines. We found that Burkitt lymphoma-derived cell line DAUDI has a
      biallelic deletion of eight of the nine analyzed genes. Moreover, we observed
      loss of expression (LOE) of the DHRS9 gene (alias RDHL), one of the deleted genes
      in the DAUDI cell line, in MOLT-14 and Raji cell lines derived from Burkitt
      lymphoma and from T-cell acute lymphoblastic leukemia, respectively. DHRS9 is
      involved in development and differentiation pathways.

PMID- 16102593
TI  - B-lymphoid or myeloid lineage identity of cell lines derived from chronic myeloid
      leukemia blast crisis.

PMID- 16102594
TI  - Functional analysis of fengycin synthetase FenD.
AB  - Fengycin is a cyclic lipopeptidic antibiotic produced nonribosomally by Bacillus
      subtilis. A fengycin synthetase mutant of B. subtilis F29-3 was generated with
      Tn917lux, which contains a transposon inserted in a 7716-bp gene, fenD. The
      mutation can be genetically complemented by transforming a plasmid carrying a
      wild-type fenD, confirming the participation of the gene in fengycin synthesis.
      Sequencing and biochemical analysis reveal that this gene encodes an enzyme that
      includes two amino acid-activating modules, FenD1 and FenD2, which activate l-Tyr
      and l-Thr, the third and the fourth amino acids in fengycin, respectively.

PMID- 16102595
TI  - The interaction between bacteria and bile.
AB  - Commensal and pathogenic microorganisms must resist the deleterious actions of
      bile in order to survive in the human gastrointestinal tract. Herein we review
      the current knowledge on the mechanisms by which Gram-positive and Gram-negative
      bacteria contend with bile stress. We describe the antimicrobial actions of bile,
      assess the variations in bile tolerance between bacterial genera and examine the
      interplay between bile stress and other stresses. The molecular mechanisms
      underlying bile tolerance are investigated and the relationship between bile and
      virulence is examined. Finally, the potential benefits of bile research are
      briefly discussed.

PMID- 16102596
TI  - Sulfur assimilation and glutathione metabolism under cadmium stress in yeast,
      protists and plants.
AB  - Glutathione (gamma-glu-cys-gly; GSH) is usually present at high concentrations in
      most living cells, being the major reservoir of non-protein reduced sulfur.
      Because of its unique redox and nucleophilic properties, GSH serves in bio
      reductive reactions as an important line of defense against reactive oxygen
      species, xenobiotics and heavy metals. GSH is synthesized from its constituent
      amino acids by two ATP-dependent reactions catalyzed by gamma-glutamylcysteine
      synthetase and glutathione synthetase. In yeast, these enzymes are found in the
      cytosol, whereas in plants they are located in the cytosol and chloroplast. In
      protists, their location is not well established. In turn, the sulfur
      assimilation pathway, which leads to cysteine biosynthesis, involves high and low
      affinity sulfate transporters, and the enzymes ATP sulfurylase, APS kinase, PAPS
      reductase or APS reductase, sulfite reductase, serine acetyl transferase, O
      acetylserine/O-acetylhomoserine sulfhydrylase and, in some organisms, also
      cystathionine beta-synthase and cystathionine gamma-lyase. The biochemical and
      genetic regulation of these pathways is affected by oxidative stress, sulfur
      deficiency and heavy metal exposure. Cells cope with heavy metal stress using
      different mechanisms, such as complexation and compartmentation. One of these
      mechanisms in some yeast, plants and protists is the enhanced synthesis of the
      heavy metal-chelating molecules GSH and phytochelatins, which are formed from GSH
      by phytochelatin synthase (PCS) in a heavy metal-dependent reaction; Cd(2+) is
      the most potent activator of PCS. In this work, we review the biochemical and
      genetic mechanisms involved in the regulation of sulfate assimilation-reduction
      and GSH metabolism when yeast, plants and protists are challenged by Cd(2+).

PMID- 16102597
TI  - Transmembrane transcriptional control (surface signalling) of the Escherichia
      coli Fec type.
AB  - The ferric citrate transport system of Escherichia coli is the first example of a
      transcription initiation mechanism that starts at the cell surface. The inducer,
      ferric citrate, binds to an outer membrane transport protein, and without further
      transport elicits a signal that is transmitted across the outer membrane, the
      periplasm, and the cytoplasmic membrane into the cytoplasm. Signal transfer
      across the three subcellular compartments is mediated by the outer membrane
      transport protein that interacts in the periplasm with a cytoplasmic
      transmembrane protein. The latter is required for activation of a sigma factor
      which belongs to the extracytoplasmic function sigma factor family. A similar
      kind of transcription regulation has been demonstrated in Pseudomonas putida, P.
      aeruginosa, Serratia marcescens, Klebsiella pneumoniae, Aerobacter aerogenes,
      Bordetella pertussis, B. bronchseptica, B. avium, and Ralstonia solanacearum. The
      genomes of P. putida, P. aeruginosa, Nitrosomonas europaea, Bacteroides
      thetaiotaomicron and Caulobacter crescentus predict the existence of many more
      such transcriptional regulatory devices.

PMID- 16102598
TI  - Haloalkaliphilic sulfur-oxidizing bacteria in soda lakes.
AB  - The existence of chemolithoautotrophic sulfur-oxidizing bacteria (SOB) capable of
      growth in an extremely alkaline and saline environment has not been recognized
      until recently. Extensive studies of saline, alkaline (soda) lakes located in
      Central Asia, Africa and North America have now revealed the presence, at
      relatively high numbers, of a new branch of obligately autotrophic SOB in these
      doubly extreme environments. Overall more than 100 strains were isolated in pure
      culture. All of them have the potential to grow optimally at around pH 10 in
      media strongly buffered with sodium carbonate/bicarbonate and cannot grow at
      pH<7.5 and Na(+) concentration <0.2 M. The majority of the isolates fell into two
      distinct groups with differing phylogeny and physiology, that have been described
      as two new genera in the Gammaproteobacteria; Thioalkalimicrobium and
      Thioalkalivibrio. The third genus, Thioalkalispira, contains a single obligate
      microaerophilic species T. microaerophila. The Thioalkalimicrobium group
      represents a typical opportunistic strategy, including highly specialized,
      relatively fast-growing and low salt-tolerant bacteria, dominating in hyposaline
      steppe soda lakes of Central Asia. The genus Thioalkalivibrio includes mostly
      slowly growing species better adapted to life in hypersaline conditions and with
      a more versatile metabolism. It includes denitrifying, thiocyanate-utilizing and
      facultatively alkaliphilic species.

PMID- 16102599
TI  - Lessons from signature-tagged mutagenesis on the infectious mechanisms of
      pathogenic bacteria.
AB  - Studies on the genetic basis of bacterial pathogenicity have been undertaken for
      almost 30 years, but the development of new genetic tools in the past 10 years
      has considerably increased the number of identified virulence factors. Signature
      tagged mutagenesis (STM) is one of the most powerful general genetic approaches,
      initially developed by David Holden and colleagues in 1995, which has now led to
      the identification of hundreds of new genes requested for virulence in a broad
      range of bacterial pathogens. We have chosen to present in this review, the most
      recent and/or most significant contributions to the understanding of the
      molecular mechanisms of bacterial pathogenicity among over 40 STM screens
      published to date. We will first briefly review the principle of the method and
      its major technical limitations. Then, selected studies will be discussed where
      genes implicated in various aspects of the infectious process have been
      identified (including tropism for specific host and/or particular tissues,
      interactions with host cells, mechanisms of survival and persistence within the
      host, and the crossing of the blood brain barrier). The examples chosen will
      cover intracellular as well as extracellular Gram-negative and Gram-positive
      pathogens.

PMID- 16102600
TI  - Transcriptional regulation of plant cell wall degradation by filamentous fungi.
AB  - Plant cell wall consists mainly of the large biopolymers cellulose,
      hemicellulose, lignin and pectin. These biopolymers are degraded by many
      microorganisms, in particular filamentous fungi, with the aid of extracellular
      enzymes. Filamentous fungi have a key role in degradation of the most abundant
      biopolymers found in nature, cellulose and hemicelluloses, and therefore are
      essential for the maintenance of the global carbon cycle. The production of plant
      cell wall degrading enzymes, cellulases, hemicellulases, ligninases and
      pectinases, is regulated mainly at the transcriptional level in filamentous
      fungi. The genes are induced in the presence of the polymers or molecules derived
      from the polymers and repressed under growth conditions where the production of
      these enzymes is not necessary, such as on glucose. The expression of the genes
      encoding the enzymes is regulated by various environmental and cellular factors,
      some of which are common while others are more unique to either a certain fungus
      or a class of enzymes. This review summarises our current knowledge on the
      transcriptional regulation, focusing on the recently characterized transcription
      factors that regulate genes coding for enzymes involved in the breakdown of plant
      cell wall biopolymers.

PMID- 16102601
TI  - Clostridium cellulolyticum: model organism of mesophilic cellulolytic clostridia.
AB  - Clostridium cellulolyticum ATCC 35319 is a non-ruminal mesophilic cellulolytic
      bacterium originally isolated from decayed grass. As with most truly cellulolytic
      clostridia, C. cellulolyticum possesses an extracellular multi-enzymatic complex,
      the cellulosome. The catalytic components of the cellulosome release soluble
      cello-oligosaccharides from cellulose providing the primary carbon substrates to
      support bacterial growth. As most cellulolytic bacteria, C. cellulolyticum was
      initially characterised by limited carbon consumption and subsequent limited
      growth in comparison to other saccharolytic clostridia. The first metabolic
      studies performed in batch cultures suggested nutrient(s) limitation and/or by
      product(s) inhibition as the reasons for this limited growth. In most recent
      investigations using chemostat cultures, metabolic flux analysis suggests a self
      intoxication of bacterial metabolism resulting from an inefficiently regulated
      carbon flow. The investigation of C. cellulolyticum physiology with cellobiose,
      as a model of soluble cellodextrin, and with pure cellulose, as a carbon source
      more closely related to lignocellulosic compounds, strengthen the idea of a
      bacterium particularly well adapted, and even restricted, to a cellulolytic
      lifestyle. The metabolic flux analysis from continuous cultures revealed that (i)
      in comparison to cellobiose, the cellulose hydrolysis by the cellulosome
      introduces an extra regulation of entering carbon flow resulting in globally
      lower metabolic fluxes on cellulose than on cellobiose, (ii) the glucose 1
      phosphate/glucose 6-phosphate branch point controls the carbon flow directed
      towards glycolysis and dissipates carbon excess towards the formation of
      cellodextrins, glycogen and exopolysaccharides, (iii) the pyruvate/acetyl-CoA
      metabolic node is essential to the regulation of electronic and energetic fluxes.
      This in-depth analysis of C. cellulolyticum metabolism has permitted the first
      attempt to engineer metabolically a cellulolytic microorganism.

PMID- 16102602
TI  - The PEP-pyruvate-oxaloacetate node as the switch point for carbon flux
      distribution in bacteria.
AB  - In many organisms, metabolite interconversion at the phosphoenolpyruvate (PEP)
      pyruvate-oxaloacetate node involves a structurally entangled set of reactions
      that interconnects the major pathways of carbon metabolism and thus, is
      responsible for the distribution of the carbon flux among catabolism, anabolism
      and energy supply of the cell. While sugar catabolism proceeds mainly via
      oxidative or non-oxidative decarboxylation of pyruvate to acetyl-CoA, anaplerosis
      and the initial steps of gluconeogenesis are accomplished by C3- (PEP- and/or
      pyruvate-) carboxylation and C4- (oxaloacetate- and/or malate-) decarboxylation,
      respectively. In contrast to the relatively uniform central metabolic pathways in
      bacteria, the set of enzymes at the PEP-pyruvate-oxaloacetate node represents a
      surprising diversity of reactions. Variable combinations are used in different
      bacteria and the question of the significance of all these reactions for growth
      and for biotechnological fermentation processes arises. This review summarizes
      what is known about the enzymes and the metabolic fluxes at the PEP-pyruvate
      oxaloacetate node in bacteria, with a particular focus on the C3-carboxylation
      and C4-decarboxylation reactions in Escherichia coli, Bacillus subtilis and
      Corynebacterium glutamicum. We discuss the activities of the enzymes, their
      regulation and their specific contribution to growth under a given condition or
      to biotechnological metabolite production. The present knowledge unequivocally
      reveals the PEP-pyruvate-oxaloacetate nodes of bacteria to be a fascinating
      target of metabolic engineering in order to achieve optimized metabolite
      production.

PMID- 16102603
TI  - Living in a fungal world: impact of fungi on soil bacterial niche development.
AB  - The colonization of land by plants appears to have coincided with the appearance
      of mycorrhiza-like fungi. Over evolutionary time, fungi have maintained their
      prominent role in the formation of mycorrhizal associations. In addition,
      however, they have been able to occupy other terrestrial niches of which the
      decomposition of recalcitrant organic matter is perhaps the most remarkable. This
      implies that, in contrast to that of aquatic organic matter decomposition,
      bacteria have not been able to monopolize decomposition processes in terrestrial
      ecosystems. The emergence of fungi in terrestrial ecosystems must have had a
      strong impact on the evolution of terrestrial bacteria. On the one hand,
      potential decomposition niches, e.g. lignin degradation, have been lost for
      bacteria, whereas on the other hand the presence of fungi has itself created new
      bacterial niches. Confrontation between bacteria and fungi is ongoing, and from
      studying contemporary interactions, we can learn about the impact that fungi
      presently have, and have had in the past, on the ecology and evolution of
      terrestrial bacteria. In the first part of this review, the focus is on niche
      differentiation between soil bacteria and fungi involved in the decomposition of
      plant-derived organic matter. Bacteria and fungi are seen to compete for simple
      plant-derived substrates and have developed antagonistic strategies. For more
      recalcitrant organic substrates, e.g. cellulose and lignin, both competitive and
      mutualistic strategies appear to have evolved. In the second part of the review,
      bacterial niches with respect to the utilization of fungal-derived substrates are
      considered. Here, several lines of development can be recognized, ranging from
      mutualistic exudate-consuming bacteria that are associated with fungal surfaces
      to endosymbiotic and mycophagous bacteria. In some cases, there are indications
      of fungal specific selection in fungus-associated bacteria, and possible
      mechanisms for such selection are discussed.

PMID- 16102604
TI  - The use of bacterial spore formers as probiotics.
AB  - The field of probiosis has emerged as a new science with applications in farming
      and aqaculture as alternatives to antibiotics as well as prophylactics in humans.
      Probiotics are being developed commercially for both human use, primarily as
      novel foods or dietary supplements, and in animal feeds for the prevention of
      gastrointestinal infections, with extensive use in the poultry and aquaculture
      industries. The impending ban of antibiotics in animal feed, the current concern
      over the spread of antibiotic resistance genes, the failure to identify new
      antibiotics and the inherent problems with developing new vaccines make a
      compelling case for developing alternative prophylactics. Among the large number
      of probiotic products in use today are bacterial spore formers, mostly of the
      genus Bacillus. Used primarily in their spore form, these products have been
      shown to prevent gastrointestinal disorders and the diversity of species used and
      their applications are astonishing. Understanding the nature of this probiotic
      effect is complicated, not only because of the complexities of understanding the
      microbial interactions that occur within the gastrointestinal tract (GIT), but
      also because Bacillus species are considered allochthonous microorganisms. This
      review summarizes the commercial applications of Bacillus probiotics. A case will
      be made that many Bacillus species should not be considered allochthonous
      microorganisms but, instead, ones that have a bimodal life cycle of growth and
      sporulation in the environment as well as within the GIT. Specific mechanisms for
      how Bacillus species can inhibit gastrointestinal infections will be covered,
      including immunomodulation and the synthesis of antimicrobials. Finally, the
      safety and licensing issues that affect the use of Bacillus species for
      commercial development will be summarized, together with evidence showing the
      growing need to evaluate the safety of individual Bacillus strains as well as
      species on a case by case by basis.

PMID- 16102605
TI  - Role of apoptosis and cytokines in influenza virus morbidity.
AB  - Influenza virus is a major human pathogen that causes epidemics and pandemics
      with increased morbidity and, especially in the elderly and those with pre
      existing medical conditions, increased mortality. Influenza is characterised by
      respiratory symptoms and constitutional symptoms. Whilst knowledge of the
      mechanisms underlying host and tissue specificity has advanced considerably of
      late we still know relatively little about other aspects of influenza virus
      virulence. In this review, we will explore what is known about the role of
      apoptosis in respiratory epithelial cell damage and the role of cytokines in
      inflammation and constitutional symptoms with particular emphasis on the link
      between apoptosis, inflammation, fever and cytokine production.

PMID- 16102606
TI  - Endoscopic ultrasound guided biopsy performed routinely in lung cancer staging
      spares futile thoracotomies: preliminary results from a randomised clinical
      trial.
AB  - BACKGROUND: Up to 45% of operations with curative intent for non-small-cell lung
      cancer (NSCLC) can be regarded as futile, apparently because the stage of the
      disease is more advanced than expected preoperatively. During the past decade
      several studies have evaluated the usefulness of endoscopic ultrasound guided
      fine needle aspiration biopsy (EUS-FNA) in lung cancer staging with promising
      results. However, no randomised trials have been performed, in which a staging
      strategy with EUS-FNA performed in all patients is compared with a conventional
      workup. METHODS: Before surgery (i.e. mediastinoscopy and subsequent thoracotomy)
      104 patients from one hospital were randomly assigned to either a conventional
      workup (CWU), including EUS-FNA only for selected patients, or a strategy where
      all patients were offered EUS-FNA (routine EUS-FNA) in addition to CWU. Patients
      were followed up for a median period of 1.3 years (range 0.2-2.4 years).
      Thoracotomy was regarded as futile if the patient had an explorative thoracotomy
      without tumour resection or if a resected patient had recurrent disease or died
      from lung cancer during follow-up. Analysis was by intention to treat. RESULTS:
      Fifty-three patients were randomly assigned to routine EUS-FNA and 51 patients to
      CWU. EUS-FNA was performed in 50 patients (94%) in the routine EUS-FNA group and
      in 14 patients (27%) in the CWU group. In the routine EUS-FNA group five patients
      (9%) had a futile thoracotomy, compared with 13 (25%) in the CWU group, p = 0.03.
      CONCLUSION: Addition of routine-EUS-FNA to standard workup in routine clinical
      practice improved selection of surgically curable patients with NSCLC.

PMID- 16102608
TI  - Gefitinib in patients with non-small cell lung cancer: symptomatic improvement
      within a few days.

PMID- 16102609
TI  - Long term results of CHART and weekly Paclitaxel in locally advanced non-small
      cell lung cancer.

PMID- 16102610
TI  - Cross-talk between cyclooxygenase-2 and epidermal growth factor receptor in non
      small cell lung cancer.

PMID- 16102611
TI  - Open repair versus endovascular treatment for asymptomatic popliteal artery
      aneurysm: results of a prospective randomized study.
AB  - PURPOSE: The aim of this prospective randomized study was to evaluate the
      relative risks and advantages of using the Hemobahn graft for popliteal artery
      aneurysm (PAA) treatment compared with open repair (OR). The primary end point
      was patency rate; secondary end points were hospital stay and length of surgical
      procedure. METHODS: The study was a prospective, randomized clinical trial
      carried out at a single center from January 1999 to December 2003. Inclusion
      criteria were an aneurysmal lesion in the popliteal artery with a diameter > or =
      2 cm at the angio-computed tomography (CT) scan, and proximal and distal neck of
      the aneurysm with a length of > 1 cm to offer a secure site of fixation of the
      stent graft. Exclusion criteria were age < 50 years old, poor distal runoff,
      contraindication to antiplatelet, anticoagulant, or thrombolytic therapy, and
      symptoms of nerve and vein compression. The enrolled patients were thereafter
      prospectively randomized in a 1-to-1 ratio between OR (group A) or endovascular
      therapy (ET) (group B). The follow-up protocol consisted of duplex ultrasound
      scan and ankle-brachial index (ABI) measured during a force leg flexion at 1, 3,
      and 6 months. Group B patients underwent an angio-CT scan and plain radiography
      of the knee with leg flexion (> 120 degrees) at 6 and 12 months, and then yearly.
      RESULTS: Between January 1999 and December 2003, 30 PAAs were performed: 15 OR
      (group A) and 15 ET (group B). Bypass and exclusion of the PAA was the preferred
      method of OR; no perioperative graft failure was observed. Twenty stent grafts
      were placed in 15 PAAs. Endograft thrombosis occurred in one patient (6.7%) in
      the postoperative period. The mean follow-up period was 46.1 months (range, 12 to
      72 months) for group A and 45.9 months (range, 12 to 65 months) for group B.
      Kaplan-Meier analysis showed a primary patency rate of 100% at 12 months for OR
      and 86.7% at 12 months with a secondary patency rate of 100% at 12 and 36 months
      for ET. No statistical differences were observed at the log-rank test. The mean
      operation time (OR, 155.3 minutes; ET, 75.4 minutes) and hospital stay (OR, 7.7
      days; ET, 4.3 days) were statistically longer for OR compared with ET (P < .01).
      CONCLUSION: We can conclude, with the power limitation of the study, that PAA
      treatment can be safely performed by using either OR or ET. ET has several
      advantages, such as quicker recovery and shorter hospital stay.

PMID- 16102612
TI  - Nonoperative approach to endotension.
AB  - OBJECTIVE: The necessity of operative treatment of endotension after endovascular
      grafting of abdominal aortic aneurysms (endovascular aneurysm repair; EVAR) is
      under debate. The proposed causes of endotension and related treatment protocols
      are controversial. We report the outcome of a nonoperative approach to five
      patients with endotension after EVAR. METHODS: From February 1997 to August 2004,
      160 patients who underwent EVAR of an infrarenal abdominal aortic aneurysm were
      evaluated for the incidence of endotension. According to the endovascular
      protocol, plain radiographs, spiral computed tomography, and angiography were
      performed before and after surgery for follow-up. To detect endotension, spiral
      computed tomography was performed by using a delayed imaging technique after the
      infusion of contrast medium. Endotension was defined as an aneurysm sac
      enlargement after EVAR without evidence of endoleak. Aneurysm sac rupture was
      defined as discontinuity of the calcific rim of the aneurysmal sac and the
      presence of intra-aneurysmal fluid outside the sac. RESULTS: We found five (3.1%)
      patients with endotension. Three of these experienced aneurysmal sac rupture.
      Only one of the three was underwent operation on experiencing sudden intestinal
      occlusion due to intra-abdominal adhesions. This patient had no intra-abdominal
      or retroperitoneal bleeding or hematoma but died after intensive care as a result
      of non-aneurysm-related problems. Four patients with endotension are still being
      closely followed up according to our surveillance protocol, and they are doing
      clinically well. After rupture, clear shrinking of the aneurysm sac was seen in
      two patients. CONCLUSIONS: Endotension after EVAR may cause subsequent aneurysm
      rupture. Endotension is evidently not associated with endoleak I to III provided
      that the endovascular graft is maintained in appropriate position and that free
      endovascular flow is observed. We propose to consider a nonoperative approach in
      the clinically asymptomatic patient with aneurysm enlargement after EVAR if
      endoleak is excluded by well-performed imaging techniques.

PMID- 16102614
TI  - Clinical implication of plasma level of soluble fibrin monomer-fibrinogen complex
      in patients with abdominal aortic aneurysm.
AB  - OBJECTIVE: We prospectively studied the clinical implication of plasma level of
      soluble fibrin monomer (FM)-fibrinogen complex, a recently established molecular
      marker reflecting thrombin activity, in patients with abdominal aortic aneurysm
      (AAA) undergoing elective aortic repair. METHODS: The study included 49 patients
      who underwent elective aneurysm repair using a gelatin-sealed or nonimpregnated
      Dacron prosthesis. Plasma level of soluble FM-fibrinogen complex was measured
      before surgery and on days 1, 3, 5, 7, and 10 postoperatively by latex
      agglutination assay utilizing monoclonal antibody IF-43. Plasma levels of
      thrombin-antithrombin complex (TAT), D-dimer, alpha2-plasmin inhibitor-plasmin
      complex (PIC), and fibrinogen were also evaluated. RESULTS: The preoperative
      level of soluble FM-fibrinogen complex showed variation in the degree of
      hemostatic activation, with fair correlations with TAT (r = 0.509, P < .001), D
      dimer (r = 0.521, P < .001), and PIC (r = 0.579, P < .001). The patients with
      greater intraoperative blood loss (> or = 800 mL) showed a significantly elevated
      plasma level of soluble FM-fibrinogen complex preoperatively compared with those
      with less intraoperative blood loss (P = .009). Its postoperative fluctuation
      showed a similar pattern to that of TAT, reflecting the time course of
      coagulation activity. Gelatin impregnation of the Dacron vascular graft did not
      seem to influence the postoperative systemic coagulation mechanism. CONCLUSIONS:
      The results indicated that soluble FM-fibrinogen complex appears to be a useful
      diagnostic molecular marker to assess the activity of the coagulation system, and
      that its preoperative level may serve as a potential risk factor for
      intraoperative hemorrhagic diathesis in patients undergoing elective AAA repair.

PMID- 16102615
TI  - Glomerular filtration rate is superior to serum creatinine for prediction of
      mortality after thoracoabdominal aortic surgery.
AB  - BACKGROUND: Clinically evident renal disease (dialysis, history of renal
      insufficiency, or serum creatinine >2.0 mg/dL) is a known risk factor for
      mortality after thoracoabdominal aortic aneurysm repair. We extended this concept
      to the questions of whether subclinical renal disease is also a risk factor and
      how best to identify subclinical disease. We hypothesized that the glomerular
      filtration rate (GFR) would be a more sensitive determinant of renal function
      than serum creatinine alone. METHODS: Between 1991 and 2004, we repaired 1106
      thoracoabdominal aortic aneurysms and descending thoracic aortic aneurysms. The
      median age was 67 years. There were 400 (36%) women and 706 (64%) men. We
      estimated GFR by using the Cockcroft-Gault equation. We divided baseline serum
      creatinine and baseline GFR into quartiles and estimated the association of the
      quartiles with 30-day postoperative mortality by chi2 testing. We further
      subdivided the population into patients with and without clinically evident renal
      disease and repeated the analysis in the patients without clinically apparent
      disease (n = 869). RESULTS: Clinically apparent renal disease was highly
      associated with 30-day mortality (odds ratio, 3.2; P < .0001). In all patients,
      serum creatinine quartile and GFR quartile were also both highly significantly
      associated with 30-day mortality (P < .0001). In patients without clinically
      apparent renal disease, both creatinine and GFR predicted additional mortality,
      but GFR was a much stronger predictor (P < .02 for creatinine vs < .0001 for
      GFR). In these patients, mortality ranged from 5% in the best GFR quartile to 27%
      in the worst. Taken as continuous variables in logistic regression equations,
      serum creatinine had no discrimination in patients without clinical disease (P =
      .73), whereas GFR remained strong (P < .0001). CONCLUSIONS: Preoperative renal
      function is an important determinant of early mortality even in patients without
      clinically evident disease. Estimated GFR is a much more powerful determinant of
      mortality risk than serum creatinine alone.

PMID- 16102616
TI  - Carotid Revascularization Using Endarterectomy or Stenting Systems (CaRESS) phase
      I clinical trial: 1-year results.
AB  - OBJECTIVE: Current clinical trials evaluating carotid stenting have focused on
      high-risk patients and may not reflect the broad population of patients with
      carotid stenosis who undergo treatment to prevent stroke. The Carotid
      Revascularization Using Endarterectomy or Stenting Systems (CaRESS) phase I study
      is a multicenter, prospective, nonrandomized trial designed to address the
      question of whether carotid stenting (CAS) with cerebral protection is comparable
      to carotid endarterectomy (CEA) in patients with symptomatic and asymptomatic
      carotid stenosis. METHODS: Patients with symptomatic (with >50% stenosis) or
      asymptomatic (with >75% stenosis) carotid stenosis were entered into the study in
      a 2:1 ratio of carotid stent and GuardWire Plus distal protection device. This
      unique trial model was developed through collaboration with the International
      Society of Endovascular Specialists, the Food and Drug Administration, the
      Centers for Medicare and Medicaid Services, the National Institutes of Health,
      and industry representatives. The primary end points included death and stroke at
      30 days and a composite 1-year end point of death, stroke, or myocardial
      infarction (MI) from 0 to 30 days and death or stroke from 31 days to 1 year. The
      secondary end points included residual stenosis, restenosis, repeat angiography,
      and carotid revascularization at 30 days and 1 year and quality-of-life changes
      at 1 year. RESULTS: A total of 397 patients (254 CEA and 143 CAS) were enrolled
      in the study: 32% were symptomatic and 68% were asymptomatic. There were no
      significant differences in patient characteristics, symptoms, or surgical risk
      profiles between groups at baseline. Kaplan-Meier analysis revealed no
      significant differences in combined death/stroke rates at 30 days (3.6% CEA vs
      2.1% CAS) or at 1 year (13.6% CEA vs 10.0% CAS). Similarly, there was no
      significant difference in the combined end point of death, stroke, or MI at 30
      days (4.4% CEA vs 2.1% CAS) or at 1 year (14.3% CEA vs 10.9% CAS). There were no
      significant differences between CEA and CAS in the secondary end points of
      residual stenosis (0% CEA vs 0.9% CAS), restenosis (3.6% CEA vs 6.3% CAS), repeat
      angiography (2.1% CEA vs 3.6% CAS), carotid revascularization (1.0% CEA vs 1.8%
      CAS), or change in quality of life (-1.56 points CEA vs -4.22 points CAS).
      CONCLUSIONS: The CaRESS phase I study suggests that the 30-day and 1-year risk of
      death, stroke, or MI with CAS is equivalent to that with CEA in symptomatic and
      asymptomatic patients with carotid stenosis.

PMID- 16102617
TI  - Carotid graft replacement: a durable option.
AB  - BACKGROUND: Carotid artery bifurcation reconstruction after endarterectomy has
      been refined over the years. Methods including primary closure, patch closure,
      and eversion endarterectomy have been proven to be durable. However, there are
      patients who require more complicated reconstructions in primary or recurrent
      disease management. Carotid replacement with a prosthetic interposition graft is
      potentially a durable option to reconstruct an artery that is technically
      unsuitable for primary or patch closure. METHODS: The charts of all carotid
      endarterectomies (n = 482) performed by the authors at our institution between
      January 1999 and December 2003 were retrospectively reviewed. Follow-up was
      performed in an Intersocietal Commission for the Accreditation of Vascular
      Laboratories-accredited vascular laboratory. Patients were divided into two main
      groups: carotid replacement with 6-mm expanded polytetrafluoroethylene (ePTFE)
      (REP) or standard endarterectomy (CEA) with or without patch closure. The
      decision for REP vs CEA (as well as the type of closure) was at the discretion of
      the surgeon according to an assessment of the end point, the distal internal
      carotid artery, and the quality and length of the endarterectomy segment.
      Interposition grafting with a 6-mm stretch of ePTFE from the transected common
      carotid to the transected internal carotid artery was performed in replacement
      reconstruction. The external carotid was ligated. Follow-up statistical analyses
      were performed with the Fisher exact test and analysis of variance for nominal
      values and t tests for continuous variables. Life table analyses were performed
      for patency and survival. RESULTS: Complete perioperative data were available for
      478 of the 482 operations performed (including all REP cases) during the study.
      At least one duplex ultrasound scan in follow-up was documented in 84% (n = 402)
      of the patients. A total of 51 were in the REP group, and 427 received CEA (95.3%
      with patch closure). Preoperative demographics, preoperative symptoms, and degree
      of stenosis did not vary within the study groups. Three 30-day surgical deaths
      occurred. The perioperative stroke rate between groups was not statistically
      different (REP, 1/51 [1.9%]; CEA, 3/427 [0.70%]; P = .35). Long-term patency and
      stroke-free survival rates at 3 years exceeded 96% and did not vary significantly
      between groups. The presence of a patch in the CEA group had no influence on
      outcomes. Duplex follow-up scan averaged two studies for at least 14 months in
      each group. Significantly more REP cases were reoperative procedures.
      CONCLUSIONS: Carotid interposition reconstruction with an ePTFE graft is an
      acceptable alternative in cases in which the standard technique would be
      technically difficult or compromising to the endarterectomy closure. Carotid
      ePTFE interposition graft replacement seems to be safe and durable and to have no
      increased perioperative risk or altered intermediate-term outcomes.

PMID- 16102618
TI  - Preoperative clinical factors predict postoperative functional outcomes after
      major lower limb amputation: an analysis of 553 consecutive patients.
AB  - BACKGROUND: Despite being a major determinant of functional independence,
      ambulation after major limb amputation has not been well studied. The purpose,
      therefore, of this study was to investigate the relationship between a variety of
      preoperative clinical characteristics and postoperative functional outcomes in
      order to formulate treatment recommendations for patients requiring major lower
      limb amputation. METHODS: From January 1998 through December 2003, 627 major limb
      amputations (37.6% below knee amputations, 4.3% through knee amputations, 34.5%
      above knee amputations, and 23.6% bilateral amputations) were performed on 553
      patients. Their mean age was 63.7 years; 55% were men, 70.2% had diabetes
      mellitus, and 91.5% had peripheral vascular disease. A retrospective review was
      performed correlating various preoperative presenting factors such as age at
      presentation, race, medical comorbidities, preoperative ambulatory status, and
      preoperative independent living status, with postoperative functional endpoints
      of prosthetic usage, survival, maintenance of ambulation, and maintenance of
      independent living status. Kaplan-Meier survival curves were constructed and
      compared by using the log-rank test. Odds ratios (OR) and hazard ratios (HR) with
      95% confidence intervals were constructed by using multiple logistic regressions
      and Cox proportional hazards models. RESULTS: Statistically significant
      preoperative factors independently associated with not wearing a prosthesis in
      order of greatest to least risk were nonambulatory before amputation (OR, 9.5),
      above knee amputation (OR, 4.4), age > 60 years (OR, 2.7), homebound but
      ambulatory status (OR, 3.0), presence of dementia (OR, 2.4), end-stage renal
      disease (OR, 2.3), and coronary artery disease (OR, 2.0). Statistically
      significant preoperative factors independently associated with death in
      decreasing order of influence included age > or = 70 years (HR, 3.1), age 60 to
      69 (HR, 2.5), and the presence of coronary artery disease (HR, 1.5).
      Statistically significant preoperative factors independently associated with
      failure of ambulation in decreasing order of influence included age > or = 70
      years (HR, 2.3), age 60 to 69 (HR, 1.6), bilateral amputation (HR, 1.8), and end
      stage renal disease (HR, 1.4). Statistically significant preoperative factors
      independently associated with failure to maintain independent living status in
      decreasing order of influence included age > or = 70 years (HR, 4.0), age 60 to
      69 (HR, 2.7), level of amputation (HR, 1.8), homebound ambulatory status (HR,
      1.6), and the presence of dementia (HR, 1.6). CONCLUSIONS: Patients with limited
      preoperative ambulatory ability, age > or = 70, dementia, end-stage renal
      disease, and advanced coronary artery disease perform poorly and should probably
      be grouped with bedridden patients, who traditionally have been best served with
      a palliative above knee amputation. Conversely, younger healthy patients with
      below knee amputations achieved functional outcomes similar to what might be
      expected after successful lower extremity revascularization. Amputation in these
      instances should probably not be considered a failure of therapy but another
      treatment option capable of extending functionality and independent living.

PMID- 16102620
TI  - Value of the duplex waveform at the common femoral artery for diagnosing
      obstructive aortoiliac disease.
AB  - PURPOSE: To evaluate the accuracy, predictive value, and observer agreement of
      the duplex ultrasound waveform at the common femoral artery as a marker of
      significant aortoiliac disease in a large group of consecutive patients who
      underwent a diagnostic workup for peripheral arterial disease in a vascular unit.
      METHODS: In 191 consecutive patients (381 aortoiliac segments), we classified the
      duplex ultrasound waveform at the common femoral artery as triphasic, biphasic,
      sharp monophasic, or poor monophasic. The waveforms were then compared with the
      findings of magnetic resonance angiography of the aortoiliac segment and
      peripheral runoff vessels. We calculated the diagnostic accuracy of the duplex
      waveform for detecting >50% obstructive disease of the aortoiliac segment and
      determined the observer agreement for classifying the duplex waveforms done by
      two independent observers. RESULTS: Magnetic resonance angiography showed
      obstruction in 152 (39.9%) of 381 aortoiliac segments in 191 patients. The
      presence of a poor monophasic waveform, encountered in 91 (24.3%) of 375
      segments, was a reliable sign of significant aortoiliac disease, with a positive
      predictive value of 92%. Other waveforms were nondiagnostic for aortoiliac
      obstructive disease. The sharp monophasic waveform reliably predicted occlusive
      disease of the superficial femoral artery that was seen in 17 of 23 instances.
      There was good observer agreement for classifying duplex waveforms (kappa(w)=
      0.85; 95% confidence interval, 0.80 to 0.89). CONCLUSION: The poor monophasic
      duplex waveform at the common femoral artery is in itself an accurate marker of
      aortoiliac obstructive disease. Other waveforms are nondiagnostic for aortoiliac
      disease.

PMID- 16102622
TI  - C-reactive protein in peripheral arterial disease: relation to severity of the
      disease and to future cardiovascular events.
AB  - BACKGROUND: Serum C-reactive protein (CRP) has proven to be an independent marker
      of the extent of atherosclerosis in patients with coronary, cerebrovascular, and
      peripheral arterial disease. In this prospective observational study, we wanted
      to assess the relationship between serum CRP and extent of disease transversely
      and longitudinally in time, as well as future cardiovascular complications in
      patients with peripheral arterial disease (PAD). Hypothesizing that CRP not only
      is a marker of but also actively participates in atherogenesis, we explored the
      possibility of CRP production by femoral atherosclerotic plaques. METHODS: Serum
      CRP was measured as highly sensitive (hsCRP) in 387 patients with PAD attending
      the vascular clinic of a university and 2 affiliated teaching hospitals. Serum
      hsCRP was related to the ankle-brachial pressure index (ABPI) as an indication of
      severity of disease at inclusion and at 12 months' follow-up and to future events
      (death and coronary, cerebral, and peripheral arterial events). In femoral
      plaques, the production of CRP was analyzed with reverse transcription-polymerase
      chain reaction, and CRP plaque localization was assessed with immunostaining on
      serial tissue sections with antibodies toward CRP, smooth muscle cells, T cells,
      and macrophages. RESULTS: The hsCRP (average +/- SD) was 3.26 +/- 2.41 mg/L.
      Serum hsCRP showed a correlation with baseline and 12-month follow-up ABPI
      (Spearman rank correlation; P < .05 for both correlations). When the patients
      were divided into three equally sized groups according to baseline serum hsCRP,
      the ABPI at baseline and at 12 months decreased significantly from the low- to
      the high-hsCRP group (baseline ABPI: 0.70, 0.65, and 0.57, P < .01; 12-month
      follow-up ABPI: 0.78, 0.70, and 0.65, P < .01). These associations persisted
      after correction for conventional risk factors. Furthermore, serum hsCRP was
      related to the combined end point "death and/or any cardiovascular event" (log
      rank test; P = .04) during a median 24-month follow-up period. Reverse
      transcription-polymerase chain reaction analysis showed CRP production in 4 of 14
      femoral plaques. CRP was detected in all femoral plaques, but not in healthy
      brachial arteries. Immunoreactivity for CRP was observed in smooth muscle cells,
      macrophages, and T cells. CONCLUSIONS: Serum hsCRP was related to the severity of
      PAD, showing a relation to future hemodynamic function and cardiovascular events
      in PAD patients. In addition to coronary plaques, aneurysmal aortas, and failed
      venous coronary bypasses, femoral plaques also produce CRP, thus illustrating
      that the production of CRP may represent a universal response to vascular injury
      and suggesting that vascular CRP may contribute to plaque development.

PMID- 16102623
TI  - Clopidogrel has no effect on D-dimer and thrombin-antithrombin III levels in
      patients with peripheral arterial disease undergoing peripheral percutaneous
      transluminal angioplasty.
AB  - OBJECTIVE: Coagulation activation markers are significantly elevated in patients
      with peripheral arterial disease compared with healthy controls. The more severe
      the disease, the higher the markers. Increased coagulation activation may
      contribute to the disease process and the risk of complications in patients with
      peripheral arterial disease, particularly after endovascular intervention. Animal
      studies have shown that clopidogrel significantly inhibits coagulation
      activation. The aim of this study was to determine whether combination of aspirin
      and clopidogrel affects thrombin-antithrombin III and D-dimer in patients with
      intermittent claudication undergoing angioplasty, compared with aspirin alone.
      METHODS: This was a double blind, randomized placebo-controlled trial conducted
      in a vascular unit in a tertiary referral center. One hundred thirty-two patients
      with intermittent claudication were randomized to clopidogrel and aspirin or
      placebo and aspirin, with a loading dose 12 hours before endovascular
      intervention. D-dimer and thrombin-antithrombin III (TAT) levels were measured
      using enzyme-linked immunosorbent assay at baseline, 1 hour before, and 1 hour,
      24 hours, and 30 days after intervention in 103 patients who underwent
      endovascular intervention. RESULTS: There was a significant rise in D-dimer
      levels at 1 hour and 24 hours after angioplasty in both groups (placebo group:
      63.69, 141.45, 122.18 ng/mL; clopidogrel group: 103.79, 159.95, 134.69 ng/mL),
      but no difference between the two groups (P = .514). Similarly there was a
      significant rise in TAT levels at 1 hour after angioplasty in both groups
      (placebo group: 2.93, 6.16 microg/L; clopidogrel group: 3.39, 5.27 microg/L),
      with no significant difference between the two groups (P = .746). CONCLUSION:
      Endovascular intervention results in a significant increase in TAT and D-dimer.
      The addition of clopidogrel to aspirin has no effect on TAT and D-dimer before or
      after endovascular intervention.

PMID- 16102624
TI  - High-energy phosphate metabolism in the calf muscle during moderate isotonic
      exercise under different degrees of cuff compression: a phosphorus 31 magnetic
      resonance spectroscopy study.
AB  - BACKGROUND: The purpose of this study was to investigate phosphocreatine (PCr)
      and inorganic phosphate levels as well as pH changes in exercising muscle at a
      workload of 4.5 W under progressive cuff stenoses, whereby the flow reduction due
      to cuff compression was quantified by flow-sensitive magnetic resonance imaging.
      METHODS: By using a whole-body 1.5-T magnetic resonance scanner and an exercise
      bench, serial phosphorus 31 (31P) magnetic resonance spectroscopy with a time
      resolution of 30 seconds was performed in 10 healthy men. Percentage changes in
      PCr, inorganic phosphate (Pi), and pH were statistically evaluated in comparison
      with baseline. The exercise protocol was characterized by a constant workload
      level of 4.5 W. Ischemic conditions were achieved by a cuff that was placed at
      the upper leg. Consecutively, increments of 0, 60, 90, 120, and 150 mm Hg were
      applied. Each increment lasted for 3 minutes. The following rest period was 10
      minutes. RESULTS: Blood flow increased significantly immediately after the onset
      of muscle exercise. No significant changes in blood flow were detected as long as
      the air pressure of the pneumatic cuff was 60 to 90 mm Hg. Significant reductions
      in blood flow were observed immediately after inflation of the cuff to 120 and
      150 mm Hg. PCr passed into a steady state during the first increment with 0 mm Hg
      and showed no substantial changes during the increment with 60, 90, and 120 mm
      Hg. PCr hydrolysis seemed progressive during the 150-mm Hg increment. Pi passed
      into a plateau level at the onset of exercise and increased significantly at the
      increment of 150 mm Hg. The pH turned into a steady state with no significant
      changes during the increments up to 120 mm Hg. At 150 mm Hg, pH decreased
      progressively. PCr levels at the end of the 150-mm Hg increment correlated
      significantly and moderately with the reduction in blood flow. CONCLUSIONS: Our
      study shows that the ischemic condition during constant muscle exercise is
      clearly characterized by PCr and Pi kinetics, as well as by pH changes. The
      correlation between the degree of blood flow reduction and PCr levels in the
      exercising muscle groups, which are supplied by the stenosed arteries, is the
      first essential of using 31P magnetic resonance spectroscopy in the assessment of
      the effect of arterial stenoses on muscle function in claudicants.

PMID- 16102625
TI  - Mesenteric stenting for chronic mesenteric ischemia.
AB  - BACKGROUND: Mesenteric stenting has not been widely adopted for the treatment of
      chronic mesenteric ischemia (CMI). The recent availability of embolic protection
      and low-profile devices with the theoretical ability to decrease perioperative
      bowel necrosis, led us to begin using mesenteric stenting for patients with CMI.
      We review our initial experience to examine short-term outcomes. METHODS: We
      performed a retrospective analysis of all patients who were treated by vascular
      surgeons with mesenteric stenting for CMI. Patients with acute mesenteric
      ischemia were excluded. We evaluated perioperative morbidity and mortality,
      restenosis, recurrent symptoms, and reintervention. Kaplan-Meier methods were
      used to assess events during follow-up. We also compared these outcomes with a
      historical control group of patients treated with open surgical
      revascularization. RESULTS: Fourteen patients underwent mesenteric stenting over
      the past 3 years. Mean age was 73, and 64% were women. There was no perioperative
      or 30-day mortality or major morbidity. Early restenosis and recurrent symptoms
      occurred in 10% and 9% of patients at 6 months. At a mean follow-up of 13 months,
      53% of patients underwent reintervention. However, 93% were symptom-free at their
      last follow-up. Compared with open surgery, stent patients had lower
      perioperative major morbidity (30% vs 0%, P < .01) and shorter hospital and
      intensive care unit length of stay (median 10 days vs 2 days, and 3 days vs 0
      days, respectively, P < .01 for both). However, stent patients were seven times
      as likely to develop restenosis (P < .01), four times more likely to develop
      recurrent symptoms (P < .01), and 15 times more likely to undergo reintervention
      (P < .01). There was one death 13 months after stenting due to mesenteric
      infarction in a patient lost to follow-up. One patient was successfully converted
      to open surgery after a second restenosis. He had regained 20 pounds and was
      determined to be a better operative candidate than at his initial presentation.
      There was no perioperative or 30-day mortality or major morbidity with
      reintervention after mesenteric stenting. CONCLUSION: Mesenteric stenting for CMI
      can be performed with low perioperative risk. However, stenting is associated
      with early restenosis and recurrent symptoms requiring secondary procedures.
      Patients with severe nutritional depletion or high surgical risk may benefit from
      mesenteric stenting for CMI, but close follow-up is required. Later open surgery
      can be performed for restenosis if nutritional status and surgical risk are
      improved, or repeat angioplasty and stenting can be effectively performed if
      operative risk remains high.

PMID- 16102626
TI  - Endovascular stenting in the treatment of pelvic vein congestion caused by
      nutcracker syndrome: lessons learned from the first five cases.
AB  - BACKGROUND: Compression of the left renal vein between the aorta and the superior
      mesenteric artery is a rare but possibly underestimated condition. Surgical
      correction (42 cases reported in the literature) can be performed by means of a
      variety of different techniques. Although endovascular stenting is well accepted
      for iliocaval occlusive disease, it has been poorly evaluated in this indication.
      We describe five patients who were treated for nutcracker syndrome by using
      stenting and analyze the nine cases previously reported. METHODS: From November
      2002 to September 2004, five women (mean age, 34.7 years) were admitted for
      endovascular treatment of a nutcracker syndrome. They all had incapacitating
      pelvic congestion syndrome, including two with a history of left ovarian vein
      embolization; moreover, two had left lumbar pain, and three had hematuria. The
      mean preoperative venous disability score was 2.4. The patients underwent a
      gynecologic examination and laparoscopy to eliminate other causes of pelvic pain.
      The laparoscopy revealed large pelvic varicose veins and no signs of
      endometriosis. Duplex scan, computed tomographic scan, and iliocavography
      revealed left renal vein compression, with proximal distention and collateral
      pathways, with dilatation and permanent reflux in the left ovarian vein in the
      three patients who had not had prior embolization. The mean renocaval pullback
      gradient was 4.3 mm Hg. A percutaneous endovascular procedure, during in which a
      self-expanding metallic stent was implanted, was performed under general
      anaesthesia. RESULTS: Technical success was achieved in all cases. One case of
      stent migration occurred: the stent was pulled down in the inferior vena cava,
      with uneventful follow-up (mean, 14.3 months). One month later, patients were all
      improved and stents were patent at the duplex scan examination, without
      restenosis. The mean venous disability score was 1. No further left ovarian vein
      reflux was evident at duplex scan in patients who did not have prior
      embolization. Pelvic pain recurred in one patient who had initially improved, and
      endometriosis was diagnosed 15 months after the procedure. Two other patients,
      who received 40-mm-long stents, had a secondary recurrence of the symptoms caused
      by stent dislodgement. The two other patients were asymptomatic. CONCLUSIONS:
      This study shows that stenting is feasible, but some guidelines should be
      followed, mainly the use of long stents protruding into the inferior vena cava.
      Stenting can eliminate the symptoms of the condition, and the technique is only
      very slightly invasive. Further experience and follow-up are needed before
      accepting such a procedure for treatment of the nutcracker syndrome.

PMID- 16102627
TI  - Palmar hyperhidrosis--which is the best level of denervation using video-assisted
      thoracoscopic sympathectomy: T2 or T3 ganglion?
AB  - PURPOSE: This study compares early results of video-assisted thoracoscopic
      sympathectomy (VTS) at the thoracic T2 versus T3 ganglion denervation levels for
      the treatment of palmar hyperhidrosis (PH). METHODS: Sixty patients with PH were
      prospectively randomized for VTS at the thoracic T2 or T3 ganglion denervation
      levels. The patients underwent postoperative evaluation on three occasions:
      before surgery, and 1 and 6 months after the operation. Endpoints included the
      absence of PH, the presence, location, and severity of compensatory hyperhidrosis
      (CH), and a quality-of-life assessment. RESULTS: Fifty-nine of 60 patients
      reported complete resolution of PH after surgery. One failure occurred in the T3
      group. CH was observed in 26 patients (86.66%) in the T2 group and in 27 patients
      (90%) in the T3 group at 1 month. At 6 months, 30 of 30 patients in the T2 group
      and 29 of 30 in the T3 group experienced CH, although in the T3 group, CH was
      less severe at both 1 and 6 months (P < .05). Quality of life was very poor in
      both groups before surgery. One month after operation, quality of life was
      improved similarly in both groups. This improvement was maintained at 6 months in
      both groups. CONCLUSION: PH is well treated by VTS at either the T2 or T3 levels.
      Denervation at the T3 level appears associated with less severe CH in the early
      postoperative period. Quality of life improved significantly in both groups.

PMID- 16102628
TI  - Transthoracic cuffed hemodialysis catheters: a method for difficult hemodialysis
      access.
AB  - BACKGROUND: Recurrent vascular access failure is a major cause of morbidity in
      patients receiving long-term hemodialysis. Central venous catheters are often
      necessary for dialysis, and easily accessed vessels (ie, the internal jugular
      vein and subclavian vein) frequently occlude because of repeated cannulation.
      When standard access sites occlude, unconventional access methods become
      necessary. We report a technique of placing hemodialysis catheters directly into
      the superior vena cava (SVC). METHODS: Between January 2002 and December 2004, 22
      patients with documented bilateral jugular and subclavian vein occlusion
      underwent transthoracic SVC permanent catheter placement. Femoral vein access was
      obtained, and a sheath was placed. Under fluoroscopic guidance, a diagnostic
      catheter was then inserted into the SVC, and a venogram was obtained. By using
      the fluoroscopic image as a reference guide, supraclavicular access directly into
      the SVC was performed with lateral and anteroposterior views to better localize
      the SVC. Once venous blood was obtained, a hydrophilic wire was passed into the
      inferior vena cava. A 5F sheath was then placed, and, with the use of an exchange
      catheter, the wire was switched for a stiffer wire. The hemodialysis catheter was
      then placed in the standard fashion over this wire. RESULTS: In a 24-month
      period, 22 patients underwent transthoracic permanent catheter placement. All
      patients had the permanent catheters successfully inserted. Two major
      complications occurred. One patient experienced a pneumothorax, and another
      patient experienced a hemothorax. Both patients were successfully treated with
      chest tube decompression. All permanent catheters functioned immediately with a
      range of 1 to 7 months. CONCLUSIONS: Transthoracic permanent catheter placement
      is an appropriate alternative for patients in whom traditional venous access
      sites are no longer available.

PMID- 16102629
TI  - Axillary-axillary interarterial chest loop conduit as an alternative for chronic
      hemodialysis access.
AB  - OBJECTIVE: After exhaustion of all conventional arteriovenous (AV) access
      options, an alternative approach is an arterioarterial conduit. The purpose of
      this study was to examine the utility of an axillary-axillary (AA) interarterial
      (IA) access in this subset of patients. METHODS: A retrospective review was
      performed of all patients who underwent placement of an AA IA access. Patients
      were observed for functional aspects and complications. Outcomes were determined
      according to the Society for Vascular Surgery/American Association for Vascular
      Surgery standards for reports for dealing with AV accesses. RESULTS: Twenty
      patients (median age, 59 years; range, 41-82 years) underwent AA IA access
      placement under general anesthesia between May 2001 and December 2004. Exhausted
      upper extremity AV access options were found in 14 patients (70%), with central
      vein occlusion in 5 patients (25%), and 12 patients (60%) had ischemia from steal
      syndrome. High-output cardiac failure was present in one patient. Median follow
      up was 7.4 months (range, 0.5-45.3 months). The 30-day perioperative mortality
      rate was 5%. There was one (5%) early access thrombosis that resulted in moderate
      ischemia. Late access thrombosis occurred in three patients (15%), and all cases
      were asymptomatic. Early postoperative bleeding necessitated surgical
      intervention in four patients (20%). Late graft infection (n = 1; 5%) occurred
      after repeated thrombectomy. The primary and secondary patency rate was 90% and
      93%, respectively, at 6 months. CONCLUSIONS: This short-term initial study showed
      that the AA IA loop access could be implanted with acceptable perioperative
      morbidity and with an excellent secondary patency rate. Further follow-up is
      necessary to determine the long-term complication rate and to allow more
      reasonable comparison with other methods of access.

PMID- 16102630
TI  - The efficacy of a new portable sequential compression device (SCD Express) in
      preventing venous stasis.
AB  - OBJECTIVE: It has been previously shown that the SCD Response Compression System,
      by sensing the postcompression refill time of the lower limbs, delivers more
      compression cycles over time, resulting in as much as a 76% increase in the total
      volume of blood expelled per hour. Extended indications for pneumatic compression
      have necessitated the introduction of portable devices. The aim of our study was
      to test the hemodynamic effectiveness of a new portable sequential compression
      system (the SCD Express), which has the ability to detect the individual refill
      time of the two lower limbs separately. METHODS: This was an open, controlled
      trial with 30 normal volunteers. The new SCD Express was compared with the SCD
      Response Compression System in the supine and semirecumbent positions. The
      refilling time sensed by the device was compared with that determined from
      velocity recordings of the superficial femoral vein using duplex ultrasonography.
      Baseline and augmented flow velocity and volume flow, including the total volume
      of blood expelled per hour during compression with the SCD Express, were compared
      with those produced by the SCD Response compression system in the same volunteers
      and positions. RESULTS: Both devices significantly increased venous flow velocity
      as much as 2.26 times baseline in supine position and 2.67 times baseline in
      semirecumbent position (all P < .001). There was a linear relationship between
      duplex ultrasonography-derived refill time and the SCD Express-derived refill
      time in both the supine (r = 0.39, P = .03) and semirecumbent (r = 0.71, P <
      .001) positions but not with the SCD Response. Refill time measured by the SCD
      Express device was significantly shorter and the cycle rate higher in comparison
      with the SCD Response in both positions. The single-cycle flow velocity and
      volume flow parameters generated by the two devices were similar in both
      positions. However, median (interquartile range) total volume of blood expelled
      per hour was slightly higher with the SCD Express device in the supine position
      (7206 mL/h [range, 5042-8437] vs 6712 mL/h [4941-10,676]; P = .85) and
      semirecumbent position (4588 mL/h [range, 3721-6252] vs 4262 mL/h [3520-5831]; P
      = .22). Peak volume of blood expelled per hour by the SCD Express device in the
      semirecumbent position was significantly increased by 10% in comparison with the
      SCD Response (P = .03). CONCLUSIONS: Flow velocity and volume flow enhancement by
      the SCD Response and SCD Express were essentially similar. The latter, a portable
      device with optional battery power that detects the individual refill time of the
      lower limbs separately, is anticipated to be associated with improved overall
      compliance and therefore optimized thromboprophylaxis. Studies testing its
      potential for improved efficacy in preventing deep vein thrombosis are justified.

PMID- 16102631
TI  - Efficacy of the treatment with prostaglandin E-1 in venous ulcers of the lower
      limbs.
AB  - BACKGROUND: Venous ulcers represent an important medical problem because of their
      high prevalence and consequent sanitary costs. In this study, we evaluated the
      effect of prostaglandin E-1 (PGE-1), a drug that improves district ischemia, on
      the healing of venous ulcers. METHODS: We performed a randomized, placebo
      controlled, single blind study in which 87 patients who had venous leg ulcers
      homogeneous for dimensions and characteristics were treated for 20 days with an
      infusion of prostaglandin E-1 or placebo, in association with topical therapy.
      The dimension and the number of the ulcers were determined at the beginning of
      the treatment and then every 20 days up to 4 months, or until total recovery. The
      main outcome of the study was the recovery percentage of the ulcers at the end of
      the 120-day period of observation and the referred healing time. The reduction in
      the extension of ulcers from the baseline measurement to the last observation was
      also evaluated. RESULTS: The baseline characteristics of the treatment and
      control groups were similar. The reduction in the size of the ulcers was faster
      in the patients treated with PGE-1. In this group, 100% of the ulcers healed < or
      = 100 days, whereas in the placebo group, only 84.2% did so by the end of the 120
      day observation period (P < .05). The estimated healing times of 25%, 50%, and
      75% of the patients treated with PGE-1 were 23, 49, and 72 days, respectively,
      compared with 52, 80, and 108 for the patients in the placebo group. Only one
      serious event occurred in the treated group. CONCLUSIONS: This study demonstrates
      the effectiveness of PGE-1 in reducing the healing time of venous ulcers,
      suggesting that venous ulcers should also be considered ischemic.

PMID- 16102632
TI  - Hemochromatosis C282Y gene mutation increases the risk of venous leg ulceration.
AB  - OBJECTIVE: Chronic venous disease (CVD) is the most common vascular disorder,
      progressing in approximately 10% of cases toward chronic venous leg ulceration,
      whereas the hemochromatosis gene (HFE) C282Y mutation is the most common
      recognized genetic defect in iron metabolism. Because CVD leads to local iron
      overload in the affected legs, we investigated whether two common HFE mutations
      could increase the risk of chronic venous leg ulceration. METHODS: This was a
      case-control study at the Vascular Diseases Center, University of Ferrara, Italy.
      From a cohort of 980 consecutive patients affected by severe CVD (CEAP clinical
      classes C4 to C6) we selected 238 cases with the exclusion of any other
      comorbidity factor potentially involved in wound etiology (group A). They were
      subdivided into group B, including 137 patients with ulcer (classes C5 and C6: 98
      primary and 39 postthrombotic cases), and group C, including 101 cases with no
      skin lesions (class C4). They were completely matched for sex, age, and
      geographic origin with 280 healthy controls (group D). A total of 518 subjects
      were polymerase chain reaction genotyped for HFE mutations (C282Y and H63D). We
      assessed the risk of ulceration by comparing the prevalence of ulcer in
      homogenous cases with and without the HFE variants. Other main outcome measures
      were the sensitivity, specificity, and predictive values of the genetic test in
      CVD cases. RESULTS: C282Y mutation significantly increases the risk of ulcer in
      primary CVD by almost seven times (odds ratio, 6.69; 95% confidence interval,
      1.45-30.8; P = .01). Application of the HFE test in primary CVD demonstrated
      increased specificity and positive predictive values (98% and 86%, respectively),
      with negligible sensitivity and negative predictive values. CONCLUSIONS: The
      overlap of primary CVD and the C282Y mutation consistently increases the risk of
      developing venous leg ulceration. These data, which have been confirmed in other
      clinical settings, suggest new strategies for preventing and treating primary
      CVD. CLINICAL RELEVANCE: The number of patients affected by primary CVD is so
      great that the vast majority of ulcers are also related to this common problem.
      On the other hand, there is not a reliable way for identifying in advance, from
      the broad base of primary CVD patients (20-40% of the general population), the
      high risk minority (10% of primary CVD cases) who will develop a venous ulcer. In
      such cases, a simple C282Y blood genetic test demonstrated an elevated
      specificity in predicting ulcer development (98%, CI 95%, 92.8-99.7). The genetic
      test could be applied starting from the C2 class, varicose veins, the most common
      situation observed in clinical practice. In perspective, the presence of the
      C282Y mutation would strengthen the indications and priorities for surgical
      correction of superficial venous insufficiency.

PMID- 16102633
TI  - Changes in superficial and perforating vein reflux after varicose vein surgery.
AB  - OBJECTIVES: This prospective duplex study was conducted to study the effect of
      current surgical treatment for primary varicose veins on the development of
      venous insufficiency < or = 2 years after varicose vein surgery. METHODS: The
      patients were part of a randomized controlled study where surgery for primary
      varicose veins was planned from a clinical examination alone or with the addition
      of preoperative duplex scanning. Postoperative duplex scanning was done at 2
      months and 2 years. RESULTS: Operations were done on 293 patients (343 legs), 74%
      of whom were women. The mean age was 47 years. In 126 legs, duplex scanning was
      done preoperatively, at 2 months and 2 years, and at 2 months and 2 years in 251
      legs. Preoperative perforating vein incompetence (PVI) was present in 64 of 126
      legs. Perforator ligation was not done on 42 of these; at 2 months, 23 of these
      legs (55%) had no PVI, and at 2 years, 25 legs (60%) had no PVI. Sixty-one legs
      had no PVI preoperatively, 5 (8%) had PVI at 2 months, and 11 (18%) had PVI at 2
      years. In the group of 251 legs, reversal of PVI between 2 months and 2 years was
      found in 28 (41%) of 68 and was more common than new PVI, which occurred in 41
      (22%) of 183 (P = .003). After 2 years, the number of legs without venous
      incompetence in which perforator surgery was not performed was 11 (26%) of 42
      legs with preoperative PVI and 18 (30%) of 61 legs without preoperative PVI, (P =
      .713). After 2 years, new vessel formation was more common in the surgically
      obliterated saphenopopliteal junction (SPJ), 4 (40%) of 10, than in the
      saphenofemoral junction (SFJ), 17 (11%) of 151(P = .027), and new incompetence in
      a previously normal junction was more common in the SFJ, 11 (18%) of 63, than in
      the SPJ, 3 (1%) of 226 (P < .001). Reflux in the great saphenous vein (GSV) below
      the knee was abolished after stripping above the knee in 17 (34%) of 50 legs at 2
      months and in 22 legs (44%) after 2 years. CONCLUSIONS: Varicose vein surgery
      induces changes in the remaining venous segments of the legs that continue for
      several months. In most patients, perforators and the GSV below the knee can be
      ignored at the primary surgery. A substantial number of recurrences in the SFJ
      and SPJ are unavoidable with present surgical knowledge because they stem from
      new vessel formation and progression of disease.

PMID- 16102634
TI  - Treatment of type II endoleaks with a novel polyurethane thrombogenic foam:
      induction of endoleak thrombosis and elimination of intra-aneurysmal pressure in
      the canine model.
AB  - OBJECTIVE: The clinical significance and treatment of retrograde collateral
      arterial perfusion of abdominal aortic aneurysms after endovascular repair (type
      II endoleak) have not been completely characterized. A canine abdominal aortic
      aneurysm model of type II endoleak with an implanted pressure transducer was used
      to evaluate the use of polyurethane foam to induce thrombosis of type II
      endoleaks. The effect on endoleak patency, intra-aneurysmal pressure, and
      thrombus histology was studied. METHODS: Prosthetic aneurysms with an
      intraluminal, solid-state, strain-gauge pressure transducer were created in the
      infrarenal aorta of 14 mongrel dogs. Aneurysm side-branch vessels were
      reimplanted into the prosthetic aneurysm of 10 animals by using a Carrel patch.
      Type II (retrograde) endoleaks were created by excluding the aneurysm from
      antegrade perfusion with an impermeable stent graft. Thrombosis of the type II
      endoleak was induced by implantation of polyurethane foam into the prosthetic
      aneurysm sac of four animals. Six animals with type II endoleaks were not
      treated. In four control animals, no collateral side branches were reimplanted,
      and therefore no endoleak was created. Intra-aneurysmal and systemic pressures
      were measured daily for 60 to 90 days after the implantation of the stent graft.
      Endoleak patency and flow were assessed during surgery and at the time of death
      by using angiographic imaging and duplex ultrasonography. Histologic analysis of
      the intra-aneurysmal thrombus was also performed. RESULTS: Intra-aneurysmal
      pressure values are indexed to systemic pressure and are represented as a
      percentage of the simultaneously obtained systemic pressure, which has a value of
      1.0. All six animals with untreated type II endoleaks maintained patency of the
      endoleak and side-branch arteries throughout the study period. Compared with
      control aneurysms that had no endoleak, animals with patent type II endoleaks
      exhibited significantly higher intra-aneurysmal pressurization (systolic
      pressure: patent type II endoleak, 0.702 +/- 0.283; control, 0.172 +/- 0.091; P <
      .001; mean pressure: endoleak, 0.784 +/- 0.229; control, 0.137 +/- 0.102; P <
      .001; pulse pressure: endoleak, 0.406 +/- 0.248; control, 0.098 +/- 0.077; P <
      .001; P < .001 for comparison for all groups by analysis of variance). Treatment
      of the type II endoleak with polyurethane foam induced thrombosis of the endoleak
      and feeding side-branch arteries in all four animals with type II endoleaks. This
      resulted in intra-aneurysmal pressures statistically indistinguishable from the
      controls (systolic pressure, 0.183 +/- 0.08; mean pressure, 0.142 +/- 0.09; pulse
      pressure, 0.054 +/- 0.04; not significant). Angiography and histology documented
      persistent patency up to the time of death (mean, 64 days) for untreated type II
      endoleaks and confirmed thrombosis of polyurethane foam-treated endoleaks in all
      cases. CONCLUSIONS: Untreated type II endoleaks were associated with intra
      aneurysmal pressures that were 70% to 80% of systemic pressure. Treatment with
      polyurethane foam resulted in a reduction of intra-aneurysmal pressure to a level
      that was indistinguishable from control aneurysms that had no endoleak. CLINICAL
      RELEVANCE: Endovascular repair of abdominal aortic aneurysms is dependent on the
      successful exclusion of the aneurysm from arterial circulation. Type II endoleaks
      originate from retrograde flow into the aneurysm sac. This study demonstrates the
      use of polyurethane foam to induce thrombosis in a canine model of a type II
      endoleak, thereby reducing intra-aneurysmal pressure to levels similar to levels
      in animals without endoleaks. This approach may be a strategy for future
      treatment of type II endoleaks.

PMID- 16102635
TI  - Decreased venous thrombosis with an oral inhibitor of P selectin.
AB  - BACKGROUND: P-selectin inhibition with protein therapeutics such as antibodies or
      soluble ligands given intravenously can decrease thrombosis in a mouse ligation
      model of venous thrombosis. In this study, we hypothesized that oral inhibition
      of P selectin with a novel oral nonprotein inhibitor (PSI-697) would decrease
      thrombosis and circulating microparticle populations. This study evaluated the
      effects on thrombosis and circulating microparticle populations in this murine
      venous thrombosis model. METHODS: Mice underwent inferior vena cava ligation to
      induce thrombosis. Mice with high circulating level of P selectin, Delta
      Cytoplasmic Tail (CT), mice gene-deleted for both E- and P-selectin knockout
      (EPKO), and wild-type C57BL/6 mice (WT) were studied without and with
      administration of PSI-697 in food (100 mg/kg daily) from 2 days before thrombosis
      until the end of the study. Animals were killed 2 and 6 days later. Evaluations
      included thrombus weight (TW), vein wall morphometrics, microparticle
      quantification by using fluorescence-activated cell sorter analysis, and vein
      wall enzyme-linked immunosorbent assays for interleukin (IL)-10, P selectin, and
      monocyte chemotactic protein 1. RESULTS: PSI-697 significantly decreased TW in WT
      and CT mice, with a treated vs nontreated TW of 132 +/- 24 vs 228 +/- 29 x 10(-4)
      g (P = .014) and 166 +/- 19 vs 281 +/- 16 x 10(-4) g (P = .001), respectively. At
      day 6, the effect was significant only in the CT group (P < .05). Drug therapy at
      day 2 significantly increased vein wall monocytes in WT mice and increased
      monocytes and total inflammatory cells in CT animals. A significant decrease in
      neutrophils and total inflammatory cells was seen in EPKO mice at day 2 with
      therapy. Therapy significantly increased platelet-derived microparticles and
      total microparticles in CT mice on day 2. Changes in treated WT and treated EPKO
      animals were not significant compared with respective vehicle treatments at day
      2. On day 6, therapy significantly decreased total microparticles in EPKO
      animals. Vein wall expression of IL-10 increased in all groups with therapy at
      day 2 (n = 18) and was significantly increased in WT (2687.5 +/- 903 pg/mL vs 636
      +/- 108 pg/mL total protein; P = .038) and CT (2078 +/- 295 pg/mL vs 432 +/- 62
      pg/mL total protein; P = .001) mice. Therapy significantly decreased vein wall P
      selectin, monocyte chemotactic protein 1, and IL-10 levels at day 6. CONCLUSIONS:
      PSI-697 decreased thrombosis. P-selectin inhibition allowed vein wall
      inflammatory cell extravasation in this model of complete ligation. Circulating
      microparticles (platelet-derived microparticles and total microparticles)
      increased with P-selectin inhibition, possibly because of decreased consumption
      into the thrombus. In summary, the oral administration of an inhibitor to P
      selectin provides significant TW reduction. CLINICAL RELEVANCE: Deep venous
      thrombosis is a significant national health problem in the general population.
      The average annual incidence of deep venous thrombosis is approximately 250,000
      cases per year. The selectin family of adhesion molecules is thought to be
      largely responsible for the initial attachment and rolling of leukocytes on
      stimulated vascular endothelium. Recent studies have explored the possible
      therapeutic implications of P-selectin inhibition to modulate venous thrombosis.
      For example, prophylactic dosing of a recombinant P-selectin ligand decreases
      venous thrombosis in a dose-dependent fashion in both feline and nonhuman primate
      animal models. Additionally, treatment of 2-day iliac thrombi with a recombinant
      protein, P-selectin inhibitor, significantly improves vein reopening in nonhuman
      primates. It is interesting to note that P-selectin inhibition decreases
      thrombosis without adverse anticoagulation. On the basis of the results from
      these previous studies, the use of P-selectin antagonism is a logical therapeutic
      approach to treat venous thrombosis. All inhibitors developed to date are either
      proteins or small molecules with low oral bioavailability that require
      intravenous or subcutaneous injection. This study evaluates, for the first time,
      a novel orally bioavailable inhibitor of P-selectin (PSI-697).

PMID- 16102636
TI  - CXC chemokine expression and synthesis in skeletal muscle during
      ischemia/reperfusion.
AB  - BACKGROUND: The chemokines keratinocyte-Derived Cytokine (KC) and macrophage
      inflammatory protein (MIP)-2, murine equivalents of human interleukin 8, have
      been implicated in remote injury after acute hind limb ischemia/reperfusion
      (I/R). These studies were designed to determine whether the cytokines responsible
      for remote tissue injury are also synthesized and accumulate in the ischemic or
      reperfused hind limb. METHODS: B6, 129SF2/J mice were subjected to either 3 hours
      of unilateral hind limb ischemia alone (IA) or 3 hours of ischemia followed by 4
      or 24 hours of reperfusion (I/R). After IA or I/R, experimental and control
      (nonischemic) contralateral hind limbs were harvested for analysis of protein
      content, messenger RNA (mRNA), tissue edema, and viability. RESULTS: IA did not
      increase KC or MIP-2 mRNA or protein levels. In contrast, I/R resulted in a 15-
      and 10-fold increase in KC mRNA after 4 and 24 hours of reperfusion,
      respectively. KC protein levels were increased 10-fold after 4 hours of
      reperfusion and 30-fold after 24 hours (vs IA or sham; P < .001). MIP-2 mRNA
      transiently increased 42-fold after 4 hours of reperfusion but decreased to basal
      levels after 24 hours of reperfusion. Despite the relative increase in MIP-2 mRNA
      by 4 hours of reperfusion, significantly increased (8- to 10 fold) MIP-2 protein
      levels were not detected until 24 hours of reperfusion only in the reperfused
      limbs. Tissue edema was increased significantly (P < .01) compared with sham
      after just 4 hours of reperfusion and remained increased at 24 hours. Tissue
      viability decreased 52% after 4 hours of reperfusion and did not change
      significantly by 24 hours. CONCLUSIONS: Skeletal muscle is a site of significant
      ongoing chemokine synthesis during reperfusion. The persistent increase in muscle
      chemokine levels at 24 hours of reperfusion was not associated with increased
      edema or injury. The role of these chemokines during reperfusion may be further
      investigated by local or oral administration of chemokines or chemokine receptor
      antagonists. CLINICAL RELEVANCE: I/R injury remains an important clinical problem
      across a variety of surgical specialties. In the critical care arena, serum
      levels of proinflammatory cytokines have been useful in predicting the mortality
      associated with acute respiratory distress syndrome and sepsis. In this article,
      the data presented indicate that murine skeletal muscle produces potent
      proinflammatory neutrophil and macrophage chemokines during reperfusion, but not
      during ischemia. These findings suggest that measurement of tissue and/or serum
      levels of chemokines during reperfusion may be an important adjunct to predicting
      tissue injury along with ongoing inflammation during the clinical course of
      reperfusion injury. Within the vascular system, severe inflammatory responses are
      usually associated with thrombotic events. New techniques to noninvasively image
      thrombin activation (by using magnetic resonance imaging) in reperfused limbs may
      coincide with the pattern of murine skeletal muscle chemokine expression in
      humans. The data suggest that reperfusion is when chemokine mRNA and protein
      synthesis increase. Within the time periods studied in these experiments, the
      chemokine component of the inflammatory response remained in the reperfused,
      rather than the systemic nonreperfused, tissue. This observation may
      underestimate the degree of the systemic response to ischemia because the single
      mouse hind limb represents only 7% of the mouse total body area, whereas the
      human limb represents nearly 18% of the adult body area. Despite this
      shortcoming, these data provide potential temporal and quantitative information
      regarding the location and magnitude of chemokine synthesis in skeletal muscle
      during reperfusion.

PMID- 16102637
TI  - Giant splenic artery aneurysms: case report and review of the literature.
AB  - Although splenic artery aneurysms (SAAs) are the most common visceral aneurysms,
      giant SAAs >10 cm in diameter have rarely been reported. We present the case of a
      67-year-old asymptomatic man who was diagnosed with a 15-cm SAA in the absence of
      a clear etiologic factor. The patient underwent open surgical repair. A medial
      visceral rotation was performed to gain good vascular control and subsequently
      the aneurysm was ligated from within. A systematic review was carried out,
      allowing us to analyze 12 cases of giant SAAs >10 cm published to date. The
      difference in terms of demographics, clinical presentation, and arterial location
      between the giant SAA group and usual SAAs may indicate a different underlying
      physiopathology that remains unclear at this time.

PMID- 16102638
TI  - Giant mycotic aneurysm of the vertebral artery: a case report.
AB  - Giant mycotic pseudoaneurysms of the vertebral artery are extremely rare. Their
      management is technically challenging because of the distorted anatomy and
      intimate relation to the lower cranial nerves. We present a rare case of a 7-year
      old boy referred to us by a pediatrician who was treating him for bacterial
      endocarditis. The pulsatile swelling measured 10 x 5 cm and was located in the
      left suboccipital triangle. The skin over the swelling was tethered to the
      underlying pulsatile swelling, suggesting prerupture syndrome. A contrast
      angiogram revealed a pseudoaneurysm from the third part of the left vertebral
      artery. Vegetations were seen on the tricuspid valve on echocardiography. Two
      step surgery was performed under the cover of antibiotics. Excision of the
      aneurysm was done after ligation of the third part of the vertebral artery. The
      postoperative period was uneventful, and there was no neurologic deficit. Repeat
      magnetic resonance angiogram revealed no residual pseudoaneurysm. The
      histopathologic examination of the specimen was suggestive of mycotic aneurysm of
      left vertebral artery.

PMID- 16102639
TI  - Intercostal artery pseudoaneurysm due to stab wound.
AB  - Intercostal artery pseudoaneurysm is extremely rare, and only six cases have been
      reported in the English literature. We describe a case of intercostal artery
      pseudoaneurysm due to a stab wound, review the literature, and discuss
      therapeutic modalities. Intercostal artery pseudoaneurysm is at risk for early
      rupture, and diagnosis before rupture is mandatory. Although embolization is
      considered to be a feasible therapeutic method, we would emphasize the
      significance of the anatomic features of the intercostal arteries: multiple blood
      supplies into the pseudoaneurysm, such as the anterior and posterior intercostal
      arteries, and musculophrenic artery.

PMID- 16102640
TI  - An alternative approach in treating an aortic arch aneurysm with an anatomic
      variant by supraaortic reconstruction and stent-graft placement.
AB  - We report the case of a 78-year-old man who presented with an aortic arch
      aneurysm that involved the origin of the left carotid artery and extended up to
      the origin of the brachiocephalic trunk. The left vertebral artery originated
      separately from the arch. The patient was treated by a reversed bifurcated
      prosthesis from the ascending aorta to the brachiocephalic trunk as well as to
      the left common carotid artery, and a simultaneous left-sided vertebral-to
      carotid artery transposition was also performed. Metachronously, the patient
      later underwent successful endovascular stent-graft placement into the entire
      aortic arch.

PMID- 16102641
TI  - Total videoscopic bypass graft implantation on the ascending aorta for lower limb
      revascularization.
AB  - An extra-anatomic bypass initiating from the ascending aorta, namely the ventral
      aorta, is a possible alternative for lower limb revascularization. However,
      acceptance of this technique is limited by the need of a median sternotomy and
      clamping of the ascending aorta. We report a new technique for the ventral aorta
      using a total videoscopic approach of the ascending aorta, which avoids the need
      for a median sternotomy. We discuss the advantages and perspectives of this new
      approach.

PMID- 16102642
TI  - Intravascular synovial sarcoma of the external iliac vein and reconstruction with
      the superficial femoral vein.
AB  - Intravascular synovial sarcoma is a rare neoplasm that arises in large veins of
      the junctional zone between the proximal leg and lower trunk in adult women.
      Herein we report the first case of an intravascular synovial sarcoma of the
      external iliac vein. It was successfully treated with neoadjuvant radiotherapy,
      radical excisional surgery, and combined arterial and venous reconstruction.
      Intravascular synovial sarcoma should be considered in the differential diagnosis
      of any adult woman with deep venous thrombosis and a mass of the femoral or iliac
      venous system.

PMID- 16102643
TI  - Endovascular repair of thoracoabdominal aortic aneurysm with multivisceral
      revascularization.

PMID- 16102644
TI  - The dynamic approach to venous disease--following in the footsteps of Gunnar
      Bauer and Robert Kistner.

PMID- 16102645
TI  - Show me the money: the ethics of physicians' income.

PMID- 16102647
TI  - Regarding "Ethics of the new economic credentialing".

PMID- 16102650
TI  - Acute diarrheal disease in children: epidemiology, prevention, and treatment.
AB  - Diarrhea is one of the most common causes of morbidity and mortality in children
      worldwide. The causes of acute diarrhea in children vary with the location, time
      of year, and population studied. There is increasing recognition of a widening
      array of enteric pathogens associated with diarrheal diseases. Adequate fluid and
      electrolyte replacement and maintenance are key to managing diarrheal illnesses.
      Thorough clinical and epidemiologic evaluation is needed to define the severity
      and type of illness, exposures, and whether the patient in is immunocompromised
      to direct the performance of selective diagnosis cultures, toxin testing,
      parasite studies, and the administration of antimicrobial therapy.

PMID- 16102649
TI  - The clinical presentation and outcomes of children infected with newly identified
      respiratory tract viruses.
AB  - Numerous emerging respiratory tract viruses have been identified as significant
      causes of acute upper and lower respiratory tract illness in children. Human
      metapneumovirus is a paramyxovirus discovered in 2001 in the Netherlands, with a
      seasonal occurrence and spectrum of clinical illness most similar to the closely
      related respiratory syncytial virus. Several new members of the corona-virus
      family have been identified, including the truly novel agent of severe acute
      respiratory syndrome and others that probably have been circulating undetected.
      Avian influenza strains have caused numerous outbreaks with high mortality,
      including children, and are potential causes of pandemic influenza. Several
      zoonotic paramyxoviruses, including Nipah and Hendra viruses, have emerged as
      occasional causes of sever outbreaks of respiratory tract illness in children and
      adults.

PMID- 16102651
TI  - Neonatal candidiasis.
AB  - In neonates born weighing less than 750 g, invasive candidates is common and
      often fatal. This situation provides an opportunity to study antifungal
      prophylaxis and treatment in this patient population, in which the
      pharmacokinetics, safety, and efficacy of antifungal products are unknown. The
      disease is less prevalent in larger, more mature, infants. Although some
      pharmacokinetic data for some products are available for term and near-term
      infants, optimal product choice, closing, and other treatment strategies also are
      unknown in this older age group.

PMID- 16102652
TI  - Fluoroquinolone antibiotics in infants and children.
AB  - The use of fluoroquinolones in children is limited because of the potential of
      these agents to induce arthropathy in juvenile animals and to potentiate
      development of bacterial resistance. No quinolone-induced cartilage toxicity as
      described in animal experiments has been documented unequivocally in patients,
      but the risk fro rapid emergence of bacterial resistance associated with
      widespread, uncontrolled fluoroquinolones use in children is a realistic threat.
      Overall, the fluoroquinolones have been safe and effective in the treatment of
      selected bacterial infections in pediatric patients. There are clearly defined
      indications for these compounds in children who are ill.

PMID- 16102653
TI  - The epidemiology of childhood pneumococcal disease in the United States in the
      era of conjugate vaccine use.
AB  - In 2000, a heptavalent pneumococcal conjugate vaccine was licensed and included
      in the schedule of routine childhood immunizations in the United States. The
      vaccine contains the serotypes most commonly associated with invasive and
      noninvasive pneumococcal infection in children and the serotypes most commonly
      expressing antibiotic resistance. Since the introduction of the vaccine, the
      incidence of invasive pneumococcal disease has declined dramatically in the
      United States, particularly among children younger than 2 years of age. The
      incidences of pneumonia and acute otitis media also have declined, but less
      substantially. Several factors may blunt the future effectiveness of the vaccine,
      however, particularly the emergence of noninvaccine pneumococcal serotypes and
      the propensity for pathogenic pneumococci to switch their capsular types, evading
      vaccine-conferred immunity.

PMID- 16102654
TI  - Infection control, hospital epidemiology, and patient safety.
AB  - Health care-acquired are a major risk for hospitalized children. Similar to adult
      patients, children are vulnerable to infections related to medical devices.
      Children also are at significant risk of nosocomial transmission of common
      pediatric viral illness, such as respiratory syncytial virus and varicella. In
      addition, pediatric patients have unique or incompletely developed immune system.

PMID- 16102655
TI  - The link between bronchiolitis and asthma.
AB  - Bronchiolitis and asthma are common wheezing illnesses of childhood. Respiratory
      syncytial virus is the main causative agent of Bronchiolitis. Rhinovirus is the
      most common trigger of exacerbations of asthma, but also has been detected
      increasingly in doing children with Bronchiolitis. Reportedly, childhood asthma
      develops in 40% of children with a history of Bronchiolitis. No convincing link
      has been reported between Bronchiolitis and development of atopy, although atopy
      generally is regarded as the main risk factor for chronic asthma. This article
      focuses on the association between bronchiolitis and the development of asthma.
      The authors address the question how respiratory syncytial virus and rhinovirus
      infections in young children, together with genetics and immunologic immaturity,
      may contribute to the development of asthma.

PMID- 16102656
TI  - The expanded spectrum of bartonellosis in children.
AB  - Bartonella spp cause various clinical syndromes immunocompetent and
      immunocompromised hosts. Domestic cats are the natural reservoir, and vectors of
      B henselae. B henselae infection usually occurs early in childhood, is generally
      asymptomatic, and in most cases revolves spontaneously. It may, however, produce
      a wide spectrum of clinical symptoms, the most frequent feature being cat-scratch
      disease. Disseminated atypical B. henselae infection may follow cat-scratch
      disease alter a symptom-free period or may present de novo mimicking a wide range
      of clinical disorders. A careful clinical history researching an intimate contact
      with a kitten associated with a specific serology and an abdominal ultrasound for
      typical hepatosplenic involvement may follow a rapid and accurate diagnosis.

PMID- 16102657
TI  - Antiretroviral therapy in HIV-infected children: the metabolic cost of improved
      survival.
AB  - Although highly active antiretroviral therapy (HAART) has positively altered the
      morality rates in HIV-infected children, these drugs have the potential to cause
      significant morbidity. These drugs cause changes in fat distribution, lipid
      profiles, glucose, homeostasis, and bone turnover. The direct relationship
      between duration of drug exposure and increased risk of cardiovascular disease is
      particularly concerning for HIV-infected infants and children, who likely will
      have longer cumulative exposure to HAART. It is unclear whether the metabolic
      effects of decades of exposure would be reversible with cessation of therapy. The
      benefits of HAART in HIV infection are indisputable, but the impetus to find a
      cure or design more tolerable therapy is clear. Infarction may replace infection
      as the major cause of morbidity and mortality from HIV.

PMID- 16102658
TI  - The treatment of children exposed to pathogens linked to bioterrorism.
AB  - Health care providers must understand the following regarding pathogens linked to
      bioterrorism: (1) the classification and qualities of possible biologic agents;
      (2) the natural history and management of biologic, chemical and radiologic
      injuries and exposures; (3) chemical agents that may be used and their
      properties; (4) different types of radiologic terrorism; (5) decontamination
      procedures; and (6) availability of antidotes and other therapeutics.

PMID- 16102659
TI  - Implications of methicillin-resistant Staphylococcus aureus as a community
      acquired pathogen in pediatric patients.
AB  - Methicillin-resistant Staphylococcus aureus is now an established community
      pathogen in many areas of the United States and the world. Community-acquired
      methicillin-resistant S aureus infections have changed several aspects of
      staphylococcal infections in children. This article discusses epidemiology,
      clinical manifestations, laboratory diagnosis, treatment, and prevention.

PMID- 16102660
TI  - The aged voice: a new hypothesis.
AB  - The anatomical changes in the senescent larynx are presented, with particular
      reference to the nonlinearity model of laryngeal biomechanics. The behavior of
      the Ishizaka-Flanagan 2-mass model in geriatric phonation suggests that an
      increase in nonlinearity can explain a number of disparate observations about the
      aged voice. Biomechanical assessment of real laryngeal tissue and experimentation
      in vivo is needed to confirm the hypothesis, leading to better paradigms of some
      phonatory disorders and perhaps to novel treatments.

PMID- 16102661
TI  - Aerodynamic measurements: normative data for children ages 6:0 to 10:11 years.
AB  - Normative measures of open quotient, speed quotient, maximum flow declination
      rate (MFDR), and subglottal pressure were determined for 75 children between the
      ages of 6 years 0 months and 10 years 11 months. The participants produced a
      sustained /a/ at low, comfort, and high pitches for a minimum of 5 seconds, and
      five to seven repetitions of /pa/ at low, comfort, and high pitches. No
      statistically significant differences were found in the mean measures of any
      aerodynamic variables (open quotient, speed quotient, maximum flow declination
      rate, subglottal pressure) between the frequency levels (low, comfort, high
      pitches). Also, no strong evidence (P > .05) exists that age or sex effect
      differed between the frequency levels (low, comfort, high) for any of the
      aerodynamic measures. For /a/ response tasks, mean open quotient measures
      increased slightly from low to comfort frequency and from comfort to high
      frequency. Mean speed quotient measures showed minimal differences between low
      and comfort frequency, with decreased mean measures for high frequency. Mean MFDR
      measures increased from low to comfort frequency and from comfort to high
      frequency. Mean subglottal pressure measures increased slightly from low to
      comfort frequency and from comfort to high frequency.

PMID- 16102662
TI  - Voice-over: perceptual and acoustic analysis of vocal features.
AB  - Voice-overs are professional voice users who use their voices to market products
      in the electronic media. The purposes of this study were to (1) analyze voice
      overed and non-overed productions of an advertising text in two groups consisting
      of 10 male professional voice-overs and 10 male non-voice-overs; and (2)
      determine specific acoustic features of voice-over productions in both groups. A
      naive group of listeners were engaged for the perceptual analysis of the recorded
      advertising text. The voice-overed production samples from both groups were
      submitted for analysis of acoustic and temporal features. The following
      parameters were analyzed: (1) the total text length, (2) the length of the three
      emphatic pauses, (3) values of the mean, (4) minimum, (5) maximum fundamental
      frequency, and (6) the semitone range. The majority of voice-overs and non-voice
      overs were correctly identified by the listeners in both productions. However
      voice-overs were more consistently correctly identified than non-voice-overs. The
      total text length was greater for voice-overs. The pause time distribution was
      statistically more homogeneous for the voice-overs. The acoustic analysis
      indicated that the voice-overs had lower values of mean, minimum, and maximum
      fundamental frequency and a greater range of semitones. The voice-overs carry the
      voice-overed production features to their non-voice-overed production.

PMID- 16102664
TI  - Scaling of voice pleasantness and acceptability in tracheoesophageal speakers.
AB  - The purpose of this study was (1) to determine the psychophysical character of
      auditory-perceptual ratings of voice pleasantness (VP) and voice acceptability
      (VA) for tracheoesophageal (TE) speakers using direct magnitude estimation (DME)
      and equal-appearing interval (EAI) scaling procedures and (2) to determine the
      relationship between listeners' ratings of VP and VA. Ten adult listeners judged
      overall VP and VA from connected speech samples produced by 20 adult male TE
      speakers. Although results yielded a prothetic continuum for VP and a metathetic
      continuum for VA, the amount of variance accounted for by a curvilinear model of
      VP was minimally more than that accounted for by a linear model. Results also
      revealed a significant relationship between VP and VA (r = 0.939). Findings from
      this study do not suggest any greater validity associated with VP and VA ratings
      obtained by the DME than the EAI method. As a result of the significant
      relationship between these ratings and to the ease of applying EAI scales, it is
      recommended that VA be used as a current clinical outcome measure. These data
      illustrate the need to identify attributes that best describe TE speech that are
      measured appropriately and are clinically useful.

PMID- 16102663
TI  - Active and passive properties of canine abduction/adduction laryngeal muscles.
AB  - Active and passive characteristics of the canine adductor- abductor muscles were
      investigated through a series of experiments conducted in vitro. Samples of
      canine posterior cricoarytenoid muscle (PCA), lateral cricoarytenoid muscle
      (LCA), and interarytenoid muscle (IA) were dissected from dog larynges excised a
      few minutes before death and kept in Krebs-Ringer solution at a temperature of 37
      degrees C +/- 1 degree C and a pH of 7.4 +/- 0.05. Active twitch and tetanic
      force was obtained in an isometric condition by applying field stimulation to the
      muscle samples through a pair of parallel-plate platinum electrodes. Force and
      elongation of the samples were obtained electronically with a dual-servo system
      (ergometer). The results indicate that the twitch contraction times of the three
      muscles are very similar, with the average of 32 +/- 1.9 ms for PCA, 29 +/- 1.6
      ms for LCA, and 32 +/- 2.4 ms for IA across all elongations. Thus, PCA, LCA, and
      IA muscles are all faster than the cricothyroid (CT) muscles but slower than the
      thyroarytenoid (TA) muscles. The tetanic force response times of these muscles
      are also similar, with a maximum rate of force increase of 0.14 N/ms.

PMID- 16102665
TI  - The impact of specific exertion on the efficiency and ease of the voice: a pilot
      study.
AB  - Even though most singers and other professional voice users are encouraged to
      relax to optimize the quality and performance of the voice, observations of
      acclaimed singers, actors, and public speakers would suggest otherwise. These
      successful vocal performers appear to be energized, actively working and exerting
      themselves. For this reason, a study was designed to explore the role of exertion
      in maintaining and optimizing the voice. The focus of this study was the
      possibility that increasing exertion could improve the voice and might result in
      the voice user experiencing less strain and, therefore, more comfort and ease.
      Ten subjects were recorded before and after completing a workshop to develop
      their skills with precise use of effort involving selected parameters of the
      larynx and vocal tract. Self-reported ratings of degree of exertion and level of
      comfort were collected at the time of each recording. The preworkshop and
      postworkshop recordings were analyzed acoustically and perceptually to compare
      the degree of noise in the signal that corresponds with the efficiency of the
      voice. The results indicated that, for all subjects, the quality of the voice
      improved with an increase in the use of specific exertion. Furthermore, ease and
      comfort also significantly increased.

PMID- 16102666
TI  - Spectral amplitude measures of adductor spasmodic dysphonic speech.
AB  - Spectral amplitude measures are sensitive to varying degrees of vocal fold
      adduction in normal speakers. This study examined the applicability of harmonic
      amplitude differences to adductor spasmodic dysphonia (ADSD) in comparison with
      normal controls. Amplitudes of the first and second harmonics (H1, H2) and of
      harmonics affiliated with the first, second, and third formants (A1, A2, A3) were
      obtained from spectra of vowels and /i/ excerpted from connected speech. Results
      indicated that these measures could be made reliably in ADSD. With the exception
      of H1(*)-H2(*), harmonic amplitude differences (H1(*)-A1, H1(*)-A2, and H1(*)
      A3(*)) exhibited significant negative linear relationships (P < 0.05) with
      clinical judgments of overall severity. The four harmonic amplitude differences
      significantly differentiated between pre-BT and post-BT productions (P < 0.05).
      After treatment, measurements from detected significant differences between ADSD
      and normal controls (P < 0.05), but measurements from /i/ did not. LTAS analysis
      of ADSD patients' speech samples proved a good fit with harmonic amplitude
      difference measures. Harmonic amplitude differences also significantly correlated
      with perceptual judgments of breathiness and roughness (P < 0.05). These findings
      demonstrate high clinical applicability for harmonic amplitude differences for
      characterizing phonation in the speech of persons with ADSD, as well as normal
      speakers, and they suggest promise for future application to other voice
      pathologies.

PMID- 16102667
TI  - The visual/kinesthetic effects of melodic contour in musical notation as it
      affects vocal timbre in singers of classical and music theater repertoire.
AB  - The purpose of this investigation was to obtain information from professional
      singers active in performing of both classical and music theater repertoire with
      regard to the visual/kinesthetic effect of melodic contour in musical notation as
      it affects vocal timbre. The evaluation of data gathered during the study
      indicates that there is reason to investigate the resulting postural shifts of
      the head and neck because they are guided by visual maps of melodic contour and
      its inversion. Significantly, it was discovered that the tone quality produced
      when a singer's head and neck postures followed the natural melodic contour of
      the melody was in no case considered to be the most pleasing of the conditions
      studied and that, in many cases, the tone quality produced when a singer's head
      and neck postures followed a map of the inversion of the melodic contour was
      judged to be much improved. The results of the study also indicate that the
      development of new technology for the general teaching studio, designed to
      address these effects, may be useful to these singers.

PMID- 16102668
TI  - Comparisons of voice onset time for trained male singers and male nonsingers
      during speaking and singing.
AB  - This study was designed to examine the temporal acoustic differences between male
      trained singers and nonsingers during speaking and singing across voiced and
      voiceless English stop consonants. Recordings were made of 5 trained singers and
      5 nonsingers, and acoustically analyzed for voice onset time (VOT). A mixed
      analysis of variance showed that the male trained singers had significantly
      longer mean VOT than did the nonsingers during voiceless stop production. Sung
      productions of voiceless stops had significantly longer mean VOTs than did the
      spoken productions. No significant differences were observed for the voiced
      stops, nor were any interactions observed. These results indicated that vocal
      training and phonatory task have a significant influence on VOT.

PMID- 16102669
TI  - Pitch discrimination and pitch matching abilities of adults who sing
      inaccurately.
AB  - Past research regarding singing ability has provided evidence that both supports
      and refutes a relationship between pitch discrimination ability and pitch
      production ability. Researchers have suggested that these skills improve with
      age. Despite this suggestion, most investigators studying singing ability have
      included only children as participants. Additionally, although many researchers
      have studied accurate singers, few have directly studied persons who do not sing
      accurately. We designed this study to examine the relationship between pitch
      discrimination ability and pitch production ability in inaccurate adult singers.
      Fifteen adults, aged 18 to 40 years, that met specific criteria qualified as
      inaccurate singers. Each participated in two tasks, a pitch discrimination task
      and a pitch production task. We used the Multi-Dimensional Voice Profile-Advanced
      (Kay Elemetrics Corporation, Lincoln Park, NJ) to determine the frequency of each
      participant's vocal productions during the pitch production task. We also used a
      Pearson product moment correlation to analyze the relationship between pitch
      discrimination and pitch production accuracy within a semitone of the target
      frequency. No meaningful relationship was found, and results were not
      statistically significant. However, the inaccurate singers in this study could be
      classified into two separate categories, those who discriminated pitches
      accurately, but produced pitches inaccurately, and those who discriminated
      pitches inaccurately and produced pitches inaccurately. These findings may be of
      great importance to music educators and impact the focus of instruction when
      teaching an inaccurate singer to sing more accurately.

PMID- 16102670
TI  - Vocal projection in actors: the long-term average spectral features that
      distinguish comfortable acting voice from voicing with maximal projection in male
      actors.
AB  - This study explored whether acoustic and perceptual features could distinguish
      comfortable from maximally projected acting voice. Thirteen professional male
      actors performed a passage from William Shakespeare's Julius Caesar twice. The
      first delivery used their comfortably projected voices, whereas the second used
      maximal projection. Acoustic measures, expert ratings, and self-ratings of
      projection and voice quality were investigated. Long-term average spectra (LTAS)
      and sound pressure level (SPL) analyses were conducted. Perceptual variables
      included projection, breathiness, roughness, and strain. When comparing the
      intensity difference between the higher (2-4 kHz) and lower (0-2 kHz) regions of
      the spectrum in voice samples from the maximal projected condition, LTAS analyses
      demonstrated increased acoustic energy in the higher part of the spectrum. This
      LTAS pattern was not as evident in the comfortable projected condition. These
      findings offered some preliminary support for the existence of an actor's formant
      (prominent peak in the upper part of the spectrum) during maximal projection.

PMID- 16102671
TI  - Common practices of voice therapists in the evaluation of patients.
AB  - This study surveys voice therapists regarding common diagnostic practices in
      patients referred for therapy with the diagnosis of muscle tension dysphonia
      (broadly defined as the "hyperfunctional" component of the dysphonia). Through
      postings on the e-mail list of the ASHA special interest division on voice,
      speech pathologists with at least 3 years' experience in stroboscopy and acoustic
      instrumentation were invited to complete the survey. Results from 53 completed
      surveys demonstrated that voice quality and patient self-perception are the sole
      assessments performed by all therapists. Voice quality, observation of body
      posture and movement, and probing the patient's ability to alter voice production
      are each significantly more likely to be performed than the more objective
      stroboscopic, acoustic, aerodynamic, and EGG assessments. Further, the tasks of
      defining specific therapy session goals and helping the patient to achieve a
      particular target skill are considered best served by measures of vocal quality,
      observation of body position and movement, and judging the patient's ability to
      alter voice production. For definition of the overall therapy goal, stroboscopy
      and patient perception scales are added to all of the subjective assessment
      measures as being important. Acoustic data are considered most important for
      patient reinforcement and outcomes assessment. Implications of these findings are
      discussed, and topics for further exploration are identified.

PMID- 16102672
TI  - The laryngology hospitalist.
AB  - The traditional pattern of medical practice is a combination of outpatient and
      inpatient care. There has been a recent trend for many specialties to separate
      this care, concentrating on only one of these spheres. A clinician caring only
      for inpatients is a Hospitalist. The care pattern for airway and swallowing
      disease adopted at the University of Maryland Hospital is in the form of the
      laryngology hospitalist. This new surgical specialty is a hybrid of an airway
      surgery subspecialist and a pure hospitalist. It offers an array of advantages to
      patients and colleague clinicians. One advantage is that of ubiquitous
      availability, which offers obvious safety benefits to patients with airway
      patency problems. Other advantages include the potential for consistent in-depth
      collaboration with other clinicians such as emergency room physicians,
      intensivists, neurologists/neurosurgeons, pulmonologists, gastroenterologists,
      speech and language pathologists, and radiologists. Financial benefits to the
      clinician include a more favorable ratio of operative disease versus total
      patient contacts. Benefits to third-party payers include the more efficient and
      timely delivery of care in the context of an inpatient stay.

PMID- 16102673
TI  - The inspiratory maneuver: a simple method to assess the superficial lamina
      propria during endoscopy.
AB  - We describe a simple means of assessing the condition of the superficial lamina
      propria during endoscopy, which we use in our practice as an adjunct to careful
      stroboscopic examination. An intake of breath against partially adducted vocal
      folds serves to draw the mucosa inferomedially into the glottis, which reveals
      areas of diminished mobility, the relationship of mucosal lesions to deeper
      tissues of the vocal folds, and subtle submucosal lesions. This is possible
      because of the unique geometry of the glottis that renders the vector forces of
      airflow different at inspiration and expiration. Because the integrity of the
      superficial lamina propria is essential to healthy phonation, we have found the
      inspiratory maneuver useful across a wide variety of mucosal pathologic
      conditions.

PMID- 16102674
TI  - Endoscope motion compensation for laryngeal high-speed videoendoscopy.
AB  - The purpose of this study was to develop and evaluate a method for automatic
      endoscopic motion compensation (MC) specialized for laryngeal high-speed
      videoendoscopy (HSV) of sustained phonation. Specifically, the left-right and
      posterior-anterior endoscopic shifts were addressed. The method is based on the
      hypothesis that the difference between endoscopic and vocal fold dynamics is
      sufficient for accurate estimation of the endoscopic motion relative to the vocal
      folds. The research questions of particular interest were as follows: is MC of
      laryngeal HSV possible at the subpixel level, and what are the validity,
      reliability, and accuracy of the proposed MC method? First, the MC accuracy was
      assessed on simulated HSV data with exactly known motion trajectories. Then, the
      accuracy and reliability of MC were evaluated on real HSV data. Finally, the
      validity of MC was established by correlating objective to perceptual ratings.
      The method demonstrated subpixel accuracy and reliable performance when tested on
      both simulated and real data. Perceptual ratings of the endoscopic motion
      demonstrated high intrarater and interrater reliabilities. Perceptual and
      quantitative assessments of endoscopic motion were in agreement. The reported
      result is encouraging for resolving a persistent problem toward building better
      methods for visual and quantitative voice assessment.

PMID- 16102675
TI  - Recurrent laryngeal nerve electrophysiologic monitoring in thyroid surgery: the
      standard of care?
AB  - Reports in the literature suggest that the rate of transient and permanent vocal
      fold immobility (VFI) after thyroid surgery is 4% to 7% and 1% to 4%. The
      intraoperative use of nerve integrity monitors has been advocated to reduce the
      incidence of VFI during thyroid surgery. The purpose of this study was to compare
      postoperative VFI after unmonitored and monitored thyroid surgical procedures.
      The charts of 136 consecutive patients who underwent thyroid surgery from 1998 to
      2003 were retrospectively surveyed. Fifty-four patients had total
      thyroidectomies, bringing the total recurrent laryngeal nerves (RLNs) dissected
      to 190. Three of 190 (1.6%) and 7 of 190 (3.7%) RLNs dissected had permanent and
      transient vocal fold dysfunction. Overall, 107 RLNs were unmonitored compared
      with 83 RLNs that were monitored. Unmonitored and monitored RLNs had a 4 of 83
      (4.8%) versus 3 of 107 (2.8%) rate of transient VFI (P > 0.05). Unmonitored and
      monitored RLNs had a 1 of 107 (0.9%) versus 2 of 83 (2.4%) rate of permanent VFD
      (P > 0.05). Electrophysiologic RLN monitoring was not demonstrated in this study
      to reduce the incidence of transient or permanent VFI after thyroid surgery.
      Electrophysiologic RLN integrity does not always translate into clinical
      postoperative vocal fold mobility. Electrophysiologic RLN monitoring may support
      that the RLN was not severed in the patient with postoperative VFI.

PMID- 16102676
TI  - Thyrohyoid approach to cidofovir injection: a case study.
AB  - Various techniques for injection into the larynx have been well described,
      including transoral injection with indirect laryngoscopy or direct laryngoscopy
      and transcutaneous injection through the thyroid cartilage or cricothyroid
      membrane. We describe a case not amenable to these techniques, in which entry
      through the thyrohyoid membrane for injection of cidofovir was successfully
      performed with a thyrohyoid approach. This technique is described, and
      comparisons are made with currently available techniques.

PMID- 16102677
TI  - How I do it: miniplate reconstruction of the lateral thyroid lamina: one-stage
      restoration of voice after teflon granuloma resection.
AB  - This case report describes a one-stage technique for long-term voice restoration
      and laryngeal reconstruction in the treatment of Teflon (Dupont, Wilmington,
      Delaware) granuloma. A patient who presented with severe dysphonia underwent
      resection of a Teflon granuloma via a lateral laryngotomy. A pedicled strap
      muscle flap was used to reconstruct the paraglottic space. The muscle flap was
      positioned through the lateral laryngotomy with direct endoscopic visualization
      of the endolarynx to ensure correct vertical positioning and medialization of the
      vocal fold. The muscle flap was secured in this position with suture fixation.
      The trapdoor piece of cartilage that was elevated to create the window in the
      lateral thyroid lamina was repositioned over the pedicled muscle flap and
      reinforced with a titanium miniplate, which was secured to the remaining thyroid
      cartilage. The patient had excellent voice results and has not required revision
      or augmentation. Reinforcement of the lateral thyroid lamina using titanium
      miniplate fixation helps to stabilize the muscle pedicle flap and the position of
      the vocal fold, in this case resulting in good long-term voice results after a
      single-stage reconstruction.

PMID- 16102679
TI  - Botulinum toxin efficacy for the treatment of pain.

PMID- 16102680
TI  - Acute lung injury, transfusion, and the anesthesiologist.

PMID- 16102681
TI  - The usefulness of the modified laryngoscopic blade for training novice
      laryngoscopists.
AB  - STUDY OBJECTIVE: The objective of this study was to evaluate the effectiveness of
      a modified Macintosh blade for reducing the chances of directly contacting the
      teeth and providing a satisfactory laryngoscopic view during laryngoscopies by
      novice laryngoscopists. DESIGN: This is a prospective clinical comparison study.
      SETTING: The study took place at an operating room of a university hospital.
      PATIENTS: Seventy-two patients with American Society of Anesthesiologists
      physical statuses I and II, aged 16 to 64 years, who were scheduled for elective
      surgery requiring general anesthesia with endotracheal tube placement
      participated in this study. INTERVENTIONS: Laryngoscopy was performed twice on
      each patient, once with a regular Macintosh no. 3 blade and once with a blade in
      which the flange was partially removed. MEASUREMENTS: As an indirect parameter
      for anticipating potential dental injury during laryngoscopy, the perpendicular
      distance from the tip of the maxillary central incisor to the flange of each
      blade (the blade-tooth distance) was measured when a novice laryngoscopist lifted
      up the laryngoscope and visualized the glottis. We compared the blade-tooth
      distances, the chances of directly contacting the tooth, laryngoscopic views, and
      the subjective feeling of difficulty in handling the laryngoscope between the 2
      blades. MAIN RESULTS: Blade-tooth distance varied significantly between the 2
      blades: the median/interquartile range was 1.2/2.3 mm vs 3.0/4.3 mm for the
      regular Macintosh no. 3 and the modified blade, respectively (P<.01). The
      modified blade was associated with decreased chances of directly contacting the
      teeth (P<.05). In addition, the modified blade provided a better laryngoscopic
      view than did the regular blade (P<.01). Most novice laryngoscopists felt that
      laryngoscopy with the modified blade was significantly easier than that with the
      regular Macintosh blade (P<.01). CONCLUSIONS: The modified Macintosh blade used
      in this study proved to be a useful device for training novice laryngoscopists
      with respect to procedure effectiveness and patient safety.

PMID- 16102682
TI  - Depth of the thoracic epidural space in paramedian approach.
AB  - STUDY OBJECTIVE: To define the depth of the thoracic epidural space in the
      paramedian axis. DESIGN: Retrospective study. SETTING: Operating room of a
      tertiary care medical center. PATIENTS: Nine hundred ninety-eight consecutive
      adults scheduled for elective major cardiothoracic/abdominal surgery and
      postoperative thoracic epidural pain control. INTERVENTIONS: The thoracic
      epidural pain control was accomplished via paramedian approach at indicated
      levels in 977 of 998 patients with uniform and well-standardized technique
      routinely performed in this institute. MEASUREMENTS: The depth of the epidural
      space, defined as the distance from the needle tip just penetrating the epidural
      layer to the overlying skin, was measured by directly checking the length markers
      displayed on the needle. Association between demographic variables and epidural
      depths at different thoracic levels was analyzed. MAIN RESULTS: The mean thoracic
      epidural depth was (mean+/-SD) 5.11+/-0.94 cm, which was positively correlated
      with the body weight (regression coefficient=0.039, P<.001) and body mass index
      but was unrelated to sex, age, or body height. On stepwise linear multivariate
      regression analysis, each 10 kg of increase in body weight would result in a 0.39
      cm increase in the depth. Besides, this paramedian depth was 0.34 cm longer at
      upper thoracic levels (T9 and upper) than that at lower levels (T10 and lower,
      P<.001). CONCLUSIONS: Body weight, body mass index, and anatomical levels
      determine the paramedian thoracic epidural depth. The greater the patient's
      weight and the higher the puncture level, the deeper the thoracic epidural space
      from the body surface.

PMID- 16102683
TI  - Propofol concentration requirement for laryngeal mask airway insertion was
      highest with the ProSeal, next highest with the Fastrach, and lowest with the
      Classic type, with target-controlled infusion.
AB  - STUDY OBJECTIVE: To determine propofol concentration of plasma 50% (Cp50,
      concentration at which there is a 50% chance that patients show no movement in
      response) for the Classic-, Fastrach-, and ProSeal-type laryngeal mask airway
      (LMA) insertion using target-controlled infusion (TCI) technique. DESIGN:
      Prospective, randomized, comparative study. SETTING: University-affiliated
      hospital. PATIENTS: Sixty American Society of Anesthesiologists physical status I
      and II women scheduled for minor gynecologic operations. INTERVENTIONS: Propofol
      TCI (Diprifusor pharmacokinetic model) was started at target concentration using
      an anesthesia pump. After reaching target effect-site concentration of propofol,
      1 of the 3 types of LMA was inserted. We recorded patient responses to LMA
      insertion as "movement" or "no movement." Test propofol concentrations started
      from a dosage of 4 microg/mL. Concentrations were then predetermined by a
      modified Dixon's up-and-down method with 0.4 microg/mL step size. MEASUREMENTS:
      Patient response to LMA insertion was classified as either of "no movement" or
      "movement." The midpoint was defined as the average concentration value of
      crossover (movement/no movement) response. The Cp50 value was defined as the
      average of the crossover midpoints in each group, and it was estimated from
      calculating the midpoints. MAIN RESULTS: Cp50 of the Classic, Fastrach, and
      ProSeal LMA insertion were 3.2+/-0.34, 4.0+/-0.22, and 4.9+/-0.20 microg/mL
      (mean+/-SD), respectively. CONCLUSION: Required propofol TCI concentrations for
      LMA insertion were significantly highest for the ProSeal, second highest for the
      Fastrach, and lowest for the Classic LMA.

PMID- 16102684
TI  - Effect of catheter site on the agreement of peripheral and central venous
      pressure measurements in neurosurgical patients.
AB  - STUDY OBJECTIVE: Previous studies suggest a correlation of central venous
      pressure (CVP) with peripheral venous pressure (PVP) in different clinical
      setups. The aim of this study was to investigate the effect of measurement site
      on PVP and its agreement with CVP in patients undergoing general anesthesia.
      DESIGN: Prospective randomized study. SETTINGS: University hospital. PATIENTS:
      Thirty patients of American Society of Anesthesiologists physical status I and II
      undergoing elective craniotomy. INTERVENTIONS: Patients were randomly assigned
      into Group A (antecubital; n=15) and Group D (dorsum hand; n=15) for antecubital
      and hand dorsum catheterization sites, respectively. Central venous pressure and
      PVP were monitored throughout the study. A total of 1925 simultaneous
      measurements were recorded at 5-minute intervals. Bland-Altman assessment for
      agreement was used for CVP and PVP in 2 groups. MEASUREMENTS: Peripheral venous
      pressure measurements were within the range of +/-2 mm Hg of CVP values, in 93.9%
      of the measurements in Group A, and in 91.2% of the measurements in Group D.
      Considering all measurements, mean bias was -0.072 mm Hg (95% CI, -0.134 to 
      0.010). Group A measurements showed a bias (CVP-PVP) of 0.173+/-3.557 mm Hg,
      whereas the bias was -0.122+/-4.322 mm Hg (mean+/-SDcorrected for repeated
      measurements) in Group D. All of the measurements were within mean+/-2SD of bias,
      which means that PVP and CVP are interchangeable in our clinical setting.
      CONCLUSION: Peripheral venous pressure measurement may be a noninvasive
      alternative for estimating CVP in patients undergoing elective neurosurgical
      operations. Measuring PVP from hand dorsum does not interfere with the agreement
      of CVP and PVP.

PMID- 16102686
TI  - Core temperature measurements through a new airway device, perilaryngeal airway
      (CobraPLA).
AB  - STUDY OBJECTIVE: The aim of this study was to test the hypothesis that the
      intraoperative pharyngeal temperatures obtained on the perilaryngeal airway
      (PLA), a novel airway device with a larger pharyngeal cuff (when inflated) than
      the laryngeal mask airway, are similar to tympanic membrane core temperatures.
      DESIGN: This study is a prospective, simultaneous device comparison. SETTING:
      This study was set at a university hospital. PATIENTS: The study patients
      included 14 adults with American Society of Anesthesiologists physical statuses I
      and II, scheduled for minor gynecological or orthopedic surgery. INTERVENTIONS: A
      PLA was inserted into the pharynx after induction of general anesthesia.
      Thermocouples were positioned at 3 sites on the PLA: (1) posterior portion of the
      head of the airway (tip), (2) midposterior portion of the cuff, and (3) left and
      right lateral-posterior portions of the cuff. Tympanic membrane thermocouples
      were inserted. MEASUREMENTS: Temperature readings from the airway and the
      tympanic membrane thermocouples were recorded every 15 minutes throughout
      surgery. MAIN RESULTS: Temperatures recorded from the lateral-posterior cuff were
      found to be virtually identical to tympanic membrane temperatures, with 97% of
      the values differing by less than 0.5 degrees C. Readings from the other 2 sites
      on the cuff differed considerably more from tympanic membrane values.
      CONCLUSIONS: These data suggest that the PLA can be adapted to monitor core
      temperature reliably.

PMID- 16102685
TI  - The effect of hemodynamic changes induced by propofol induction on cerebral
      oxygenation in young and elderly patients.
AB  - STUDY OBJECTIVE: To investigate the difference of regional cerebral oxygen
      saturation (rSo2) decrease in response to the decrease in mean arterial blood
      pressure (MAP) in young and elderly patients. DESIGN: Prospective clinical study.
      SETTING: Medical center hospital. PATIENTS: Twenty-four American Society of
      Anesthesiologists physical status I and II patients, 12 of whom were young and
      the other 12 elderly, scheduled for elective surgery requiring general
      anesthesia. Patients received propofol 2 mg/kg (young patient group) and propofol
      1.5 mg/kg (elderly patient group) as an induction drug. MEASUREMENTS: MAP and
      rSo2 were recorded continuously for 5 minutes after propofol administration. MAIN
      RESULTS: MAP values at the second to fifth minutes and rSo2 at the second minute
      after propofol administration were significantly lower than baseline in both
      groups (P<.05). The rSo2 decrease was minimal, and the slopes of the rSo2
      decrease in response to the MAP decrease in the young and elderly groups were
      0.093+/-0.012 (P<.001) and 0.112+/-0.016 (P<.001) (mean+/-SEM), respectively.
      CONCLUSIONS: After propofol induction, there was no difference between young and
      elderly patients in rSo2 decrease in response to the decrease in MAP.

PMID- 16102687
TI  - Periorbital pain associated with hemifacial spasms that responded to botulinum
      toxin treatment and microvascular decompression surgery: a case report.
AB  - Periorbital pain is unusual in patients with blepharospasms. We report a patient
      with hemifacial spasms who presented with severe ipsilateral periorbital aching
      pain. After treatment with botulinum toxin type A, the left hemifacial spasms and
      left periorbital pain improved temporarily. Microvascular decompression surgery
      was then performed for the facial spasms. The patient's left hemifacial spasms
      disappeared immediately after the operation, and his left periorbital pain was
      also totally resolved.

PMID- 16102688
TI  - Transfusion-related acute lung injury--does the anesthesiologist need to worry
      about this?
AB  - Transfusion-related acute lung injury (TRALI) is a complication associated with
      blood product administration. Although it is well described in the critical care
      and hematology literature, there is a paucity of information found in the
      anesthesiology literature. Because most transfusions are administered in the
      surgical arena, it is important that anesthesiologists be aware of TRALI and its
      clinical implications. We present a case of TRALI in a 55-year-old man who
      received a single unit of packed red blood cells during a single-level lumbar
      laminectomy. We also review the etiology, pathophysiology, and diagnostic
      criteria of TRALI.

PMID- 16102689
TI  - Laryngeal nerve monitoring during thyroid surgery in pregnancy.
AB  - A 32-week parturient required partial thyroidectomy for suspicious carcinoma. The
      surgeon requested laryngeal nerve monitoring to decrease the chances of laryngeal
      nerve injury during surgery. After rapid-sequence induction of general anesthesia
      and intubation, a size 3 laryngeal mask airway was inserted posterior to the
      endotracheal tube and the cuff inflated with 15 mL of air. A fiberoptic
      bronchoscope inserted through the laryngeal mask airway provided an unhindered
      view of vocal cords for laryngeal nerve identification and testing during
      surgery. This combined technique also offered the advantages of a secured airway,
      as well as positive pressure ventilation in the parturient during thyroid
      surgery.

PMID- 16102690
TI  - Recurrent ST-segment elevations in a patient without significant coronary
      disease.
AB  - We report a case of recurrent ST-segment elevations totaling 7 times over 3 hours
      during subtotal gastrectomy and the early postoperative period in a patient with
      no history of coronary artery disease. Possible contributing factors include cold
      stimulus, epidural anesthesia, and inadequate depth of anesthesia. The first
      episode almost resulted in cardiac arrest and was treated with intravenous
      epinephrine. The second episode was associated with ventricular fibrillation,
      which was treated with defibrillation and intravenous verapamil. The third to the
      seventh episodes were successfully treated with intravenous nitrate. The
      electrocardiographic changes and postoperative coronary angiography were
      consistent with a clinical diagnosis of coronary artery spasm. This case suggests
      that coronary artery spasm is capable of occurring repeatedly in a cyclic pattern
      during perioperative periods.

PMID- 16102691
TI  - Subdural hematoma after atraumatic spinal.
AB  - We report a case of subdural hematoma in a 68-year-old white man who underwent
      left inguinal hernia repair with spinal anesthesia. The patient had a postdural
      puncture headache (PDPH) on postoperative day 4, but he refused invasive
      treatment. Instead, he self-administered acetaminophen, aspirin, and caffeine. On
      postoperative day 11, he was diagnosed with a subdural hematoma. At 49 days
      postoperatively, a computed axial tomographic scan was taken, the results of
      which were normal, after no surgical intervention. This patient had none of the
      risk factors as reported in the literature for this rare complication. Although a
      headache postoperatively, after spinal anesthesia, is often assumed to be PDPH,
      clinicians should not rule out the possibility of subdural hematoma, especially
      if the headache is persistent. We advise that the smallest-bore spinal needles be
      used when administering spinal anesthesia and that patients be carefully
      evaluated before their surgery for use of anticoagulants, herbal medications, or
      history of cerebrovascular disease. Immediate treatment of the PDPH with an
      epidural blood patch should be considered. If a patient refuses invasive
      treatment, he should be counseled for the possibility of subdural hematoma. The
      patient also should be advised to avoid medications with anticoagulant
      properties.

PMID- 16102692
TI  - Does the evidence support the use of spinal and epidural anesthesia for surgery?
AB  - When spinal and epidural anesthesia were introduced into clinical practice, their
      primary use was as an alternative to general anesthesia. Later, largely as a
      result of the realization that opioids could be safely and effectively used to
      produce selective spinal analgesia, spinal and epidural (neuraxial) analgesia
      began to be used specifically for the treatment of perioperative pain. We present
      a systematic review of the literature on neuraxial anesthesia and analgesia, new
      meta-analyses that illustrate the powerful effect of improvements in
      perioperative safety in general on the ability of neuraxial techniques to make a
      difference, and a consideration of why a literature analysis does not provide
      clear answers.

PMID- 16102693
TI  - Teaching professionalism during anesthesiology training.
AB  - Recently, there has been a focus on the teaching of professionalism in
      postgraduate medical education. Many discussions and studies have been performed
      to help in teaching professionalism and in the evaluation of the effectiveness of
      this teaching process. Unfortunately, many anesthesiologists are unaware of the
      literature and the discussions that have taken place. This review article serves
      as a primer for those individuals faced with the task of instilling the concepts
      of professionalism, not only in trainees but also in anesthesiologists practicing
      today.

PMID- 16102694
TI  - Leroy D Vandam, MD: an anesthesia journey.
AB  - Leroy D Vandam, MD was a remarkable man--an intricate amalgamation of an artist,
      scientist, and physician. He was a bastion of medical historical knowledge. Dr
      Vandam became a most influential anesthesiologist, some say, a giant. He was an
      example of someone who, with resolve, overcame adversity. His artwork is
      displayed in countless places, and several of his paintings form part of the Wood
      Library Museum Heritage Series. Dr Vandam was first a surgeon, but he abandoned
      surgery and pursued a career in anesthesiology under the leadership of Robert
      Dripps. He completed his residency training at the University of Pennsylvania and
      joined its staff in 1949. When he arrived at Brigham and Women's Hospital in the
      1950s as director of anesthesia, he embarked on one of the most illustrious
      careers in American anesthesiology. Dr Vandam published more than 250 original
      articles, chapters, abstracts, and other reports on a wide variety of subjects
      including history, art, and pharmacology. His classic article on the
      complications of neuroaxial blocks is a seminal work in anesthesiology. This
      article describes how an anesthesiologist who shared an interest with Dr Vandam
      in the history of anesthesiology came to produce a movie based on his career, the
      evolution of anesthesia equipment, and the transformation of our specialty.

PMID- 16102695
TI  - Patients want an anesthesiologist to plan and be in charge of their anesthesia.

PMID- 16102696
TI  - The Baxter AS50 syringe driver can be used safely in the MRI suite.

PMID- 16102697
TI  - The airway approach algorithm: practical airway assessment.

PMID- 16102699
TI  - Detection of oxygen face mask defect by gas analysis during ambulatory surgery.

PMID- 16102700
TI  - Quick fix of bent prongs of the thermodilution cardiac output connector of a Swan
      Ganz catheter.

PMID- 16102701
TI  - The use of a gum elastic bougie in combination with a videolaryngoscope.

PMID- 16102702
TI  - Watch your back!

PMID- 16102703
TI  - Introduction of ASPAN'S Evidence-based Practice Model.

PMID- 16102704
TI  - Nurses' diagnoses and treatment decisions regarding care of the agitated child.
AB  - Postoperative agitation has many potential etiologies and remains a significant
      clinical issue in the pediatric PACU setting. Caring for the agitated child
      requires a thorough assessment and calls for targeted interventions. This
      observational study evaluated nurses' diagnoses and treatment decisions regarding
      care of the agitated child. Nurses were observed during their care of 194
      agitated children over a 3-month period. Pain and anxiety were the most commonly
      identified sources of agitation in the pediatric PACU setting (27% and 25% of
      cases, respectively), and nurses' targeted, primary interventions for these
      problems were fairly effective (48% and 67% effective, respectively). Anesthesia
      induced agitation was less often identified as the etiology (11%), and primary
      interventions were more varied and less effective (38%). Physiologic
      abnormalities were identified as the source for agitation in only 3 cases, but
      went unrecognized for an extended period in 2 children. Results of this study
      underscore the complexity of assessment and treatment decisions when caring for
      agitated children. A decision algorithm based on this study is described as a
      potential aid toward differentiation of agitation and appropriate intervention.

PMID- 16102705
TI  - Self-care activities for postdischarge nausea and vomiting.
AB  - Postdischarge nausea and vomiting (PDNV) is a serious threat to the recovery of
      ambulatory surgical patients. Pharmacological interventions available before
      discharge are not readily available to the patient after discharge; therefore,
      the activities that patients perform to manage new-onset PDNV may affect their
      surgical recovery. Assembled from a comprehensive study of PDNV, this paper
      describes the self-care activities that ambulatory patients use to manage new
      onset nausea and vomiting after discharge. The findings have implications for
      patient education and future research.

PMID- 16102706
TI  - Patient-controlled modalities for acute postoperative pain management.
AB  - Although numerous clinical practice guidelines for pain management have been
      published throughout the last 12 years, inadequate pain relief remains a
      significant health care issue. Several patient-controlled analgesia (PCA)
      modalities are currently available for the treatment of acute postoperative pain,
      including intravenous (IV) PCA, epidural (PCEA), and oral PCA. Although PCEA and
      IV PCA are both commonly used modalities, IV PCA is considered the standard of
      care for postoperative pain management. Limitations of this modality do exist,
      however. Consequently, noninvasive PCA systems are under development to
      circumvent many of these limitations, including the fentanyl hydrochloride
      patient-controlled transdermal system (PCTS); (IONSYS Ortho-McNeil
      Pharmaceutical, Raritan, NJ) and a number of patient-controlled intranasal
      analgesia (PCINA) delivery systems. The objective of this article is to review
      the PCA modalities currently in use and to discuss those in development for the
      treatment of acute postoperative pain.

PMID- 16102707
TI  - Domestic violence: caring for a colleague.
AB  - Domestic abuse is a devastating social, legal, and health care problem of
      enormous proportions. Routine and multiple screenings by skilled health care
      providers, when conducted face-to-face, markedly increase the identification of
      physical, psychological, and sexual abuse. Patients are not the only ones who can
      benefit from domestic violence screening and intervention. This article describes
      the subtle signs of domestic abuse that might be observed in a colleague,
      explains how to initiate a conversation with a colleague, and suggests
      appropriate ways to offer support.

PMID- 16102708
TI  - Hot topics for accredited health care organizations.

PMID- 16102709
TI  - Fentanyl for acute pain management.

PMID- 16102710
TI  - The patient with latex allergy.

PMID- 16102711
TI  - Dexmedetomidine--does it have a role in the perioperative setting?

PMID- 16102715
TI  - ABCs for living.

PMID- 16102716
TI  - Currents and photocurrents in organic materials determined by the interface
      phenomena.
AB  - The role of interface between molecular material and electrode on currents and
      photocurrents is considered. Mechanisms of charge carrier injection, electrode
      recombination and transport are discussed. Particularly thermal, excitonic, photo
      and tunneling injection of charge carriers, diffusion in presence of image force,
      interface barrier between electrode and organic materials and two organic
      materials, non-uniformity of electrodes and other phenomena on charge carrier
      injection are considered. The data presented in the review which complete
      theoretical considerations have been taken from previous as well as current
      literature. The considered phenomena are very important for the analysis of many
      practical problems for molecular electronic devices such as rectification of
      current, organic transistors, electroluminescence, photovoltaic effects and some
      similar problems.

PMID- 16102717
TI  - A surface plasmon resonance-based assay for small molecule inhibitors of human
      cyclophilin A.
AB  - A simple protocol for generating a highly stable and active surface plasmon
      resonance (SPR) sensor surface of recombinant human hexahistidine cyclophilin A
      (His-CypA) is described. The sensor surface was sensitive and stable enough to
      allow, for the first time, the screening and ranking of several novel small
      molecule (Mr approximately 250-500 Da) ligands in a competition binding assay
      with cyclosporin A (CsA). It also allowed us to accurately determine the kinetic
      rate constants for the interaction between His-CypA and CsA. His-CypA was first
      captured on a Ni2+-nitrilotriacetic acid (NTA) sensor chip and was then briefly
      covalently stabilized, coupling via primary amines. The significant baseline
      drift observed due to dissociation of weakly bound His-CypA from the Ni2+-NTA
      moiety was eliminated, resulting in a surface that was stable for at least 36 h.
      In addition, immobilized protein activity levels were high, typically between 85
      and 95%, assayed by the interaction between His-CypA and CsA. The mean
      equilibrium dissociation constant for CsA (K(dCsA)) binding to the immobilized
      His-CypA was 23+/-6 nM, with on and off rates of 0.53+/-0.1 microM(-1) s(-1) and
      1.2+/-0.1 (x 10(-2)) s(-1), respectively. These values agree well with the values
      for the corresponding binding constants determined from steady-state and kinetic
      fluorescence titrations in solution.

PMID- 16102718
TI  - Sequence confirmation of synthetic phosphorothioate oligodeoxynucleotides using
      Sanger sequencing reactions in combination with mass spectrometry.
AB  - A protocol relying on Sanger sequencing reactions in combination with mass
      spectrometry (MS) for sequence confirmation of antisense phosphorothioate
      oligodeoxynucleotides is described. In this procedure, synthetic phosphorothioate
      oligodeoxynucleotides are used as reverse primers for extension of matched
      templates with enough length (approximately 150-300 bp) for well-established
      Sanger sequencing. Because the complementary strand of modified primer is used
      directly for sequencing primer extension, the base order shown in the sequencing
      result is reversely complementary to phosphorothioate oligodeoxynucleotide. This
      sequencing method can be applied not only to phosphorothioate
      oligodeoxynucleotides with different lengths (13-21 mer) and base composition but
      also to sequences with bases' switch, deletion, or insertion. In addition,
      modified primers incorporate the 5' end of polymerase chain reaction (PCR)
      products conveying the characters of phosphorothioate modification. The method
      requires only common reagents and instruments and so is better suited to routine
      sequence analysis in quality control of phosphorothioate antisense drugs.

PMID- 16102719
TI  - The introduction of sit-stand worktables; aspects of attitudes, compliance and
      satisfaction.
AB  - The introduction of sit-stand worktables was examined in this study. Purchasers
      at four companies were interviewed regarding preparations prior to purchase,
      follow-up after installation, and if expectations had been fulfilled. Personnel
      at the four companies answered a questionnaire examining use of the worktables'
      sit-stand function, and the influence of some variables on this. Utilisation of
      the sit-stand function was less than what could be expected to relieve static
      musculoskeletal loading during VDU work. Pain experienced during the past year,
      and education on the use of the worktable gave rise to modest increases in
      utilisation. Investment in sit-stand worktables was satisfactory to purchasers,
      in terms of providing flexible furniture to suit modern organisational dynamics.
      Users were, in general, positive to the worktables, but showed poor compliance in
      using them. User and purchaser satisfaction with regard to improving individual
      health ergonomics was questionable in respect of the low level of usage.

PMID- 16102720
TI  - Effects of low stereo acuity on performance, presence and sickness within a
      virtual environment.
AB  - To examine the effect of stereo vision on performance, presence and oculomotor
      disturbances within a virtual environment (VE), two groups of 23 participants
      (good stereo acuity/low stereo acuity) were evaluated. Groups were matched in
      terms of gender, age and VE design factors (the latter were accounted for to
      ensure a similar VE experience between groups). Participants were immersed in a
      VE maze for up to 1h during which time they interacted with the environment while
      performing a number of stationary and movement-based tasks. Individuals with low
      stereo acuity traveled further to complete two tasks in the VE, yet performance
      time on these tasks was comparable to participants with good stereo acuity.
      Although participants with impaired stereo vision likely did not fully benefit
      from a stereoscopic view of the scene, they may have received sufficient depth
      information from movement-based cues to efficiently accomplish these tasks in a
      comparable amount of time. Overall performance, based on both the number of tasks
      completed and the total translational distance moved (based on input device
      movement) within the VE was not hindered for those with low stereo acuity. In
      addition, the expected increase in oculomotor disturbances for this group was not
      evident in this study, and both groups reported comparable amounts of presence
      from VE exposure. These results suggest that when head tracking is included as
      part of the VE experience (i.e., motion parallax cues exist), participants with
      low stereo acuity can be expected to perform comparable to normal sighted
      individuals, experience a comparable sense of presence, and report no increase in
      adverse effects when viewing scenes via stereoscopic displays. Thus, motion
      parallax cues may adequately provide a sense of depth within a VE, and alleviate
      theorized performance decrements for individuals with low stereo acuity. The
      results of this study have implications for those designing entertainment
      simulations or other such applications open to the general public, where people
      with low stereo acuity may routinely participate.

PMID- 16102721
TI  - Synchronous and asynchronous presentations of auditory and visual signals:
      Implications for control console design.
AB  - In this study, the effects of synchronous and asynchronous auditory and visual
      signal presentation on reaction times and response errors were examined to
      provide data for developing ergonomics recommendations for control console
      design. The results showed that synchronous presentation for combined visual and
      auditory stimulation facilitated responses, and shorter reaction times and higher
      response accuracies were obtained. When visual and auditory stimuli were
      presented synchronously but in opposing (left and right) positions, a visual
      dominance phenomenon was found, such that the subjects responded more often (81%)
      with faster responses to the visual signal. This visual dominance effect occurred
      even in the asynchronous condition when the auditory stimulus was presented 200
      ms earlier than the visual one. It was also found that response speed and
      accuracy improved with increasing length of the warning time interval, and when
      an uncrossed hand posture was used for making responses. The above results were
      translated into practical ergonomic recommendations for response key layout,
      warning time interval, and ways of presenting visual and auditory signals to
      improve control console design.

PMID- 16102722
TI  - Expression of cyclic nucleotide phosphodiesterase 3A in isolated rat
      submandibular acini.
AB  - Phosphodiesterase (PDE) 3 has been characterized in isolated rat submandibular
      acini. PDE3 activity was detected in homogenates of isolated rat submandibular
      acini; little or no PDE3 activity was found in ducts. About 62% of PDE3 activity
      in the acini was recovered in the supernatant fractions; 38% in particulate
      fractions. In the acini, but not ducts, PDE3A mRNA was detected by reverse
      transcriptase-polymerase chain reaction (RT-PCR). The PDE3-specific inhibitor,
      cilostamide, increased the ratio of apomucin mRNA/18s rRNA, as quantified by real
      time RT-PCR. Our results indicate that PDE3A may be important in regulating cAMP
      pools that control acini functions.

PMID- 16102723
TI  - New mutant Chinese hamster ovary cell representing an unknown gene for attachment
      of glycosylphosphatidylinositol to proteins.
AB  - Aerolysin, a secreted bacterial toxin from Aeromonas hydrophila, binds to
      glycosylphosphatidylinositol (GPI)-anchored protein and kills the cells by
      forming pores. Both GPI and N-glycan moieties of GPI-anchored proteins are
      involved in efficient binding of aerolysin. We isolated various Chinese hamster
      ovary (CHO) mutant cells resistant to aerolysin. Among them, CHOPA41.3 mutant
      cells showed several-fold decreased expression of GPI-anchored proteins. After
      transfection of N-acetylglucosamine transferase I (GnT1) cDNA, aerolysin was
      efficiently bound to the cells, indicating that the resistance against aerolysin
      in this cells was mainly ascribed to the defect of N-glycan maturation. CHOPA41.3
      cells also accumulated GPI intermediates lacking ethanolamine phosphate
      modification on the first mannose. After stable transfection of PIG-N cDNA
      encoding GPI-ethanolamine phosphate transferase1, a profile of accumulated GPI
      intermediates became similar to that of GPI transamidase mutant cells. It
      indicated, therefore, that CHOPA41.3 cells are defective in GnT1, ethanolamine
      phosphate modification of the first mannose, and attachment of GPI to proteins.
      The GPI accumulation in CHOPA41.3 cells carrying PIG-N cDNA was not normalized
      after transfection with cDNAs of all known components in GPI transamidase
      complex. Microsomes from CHOPA41.3 cells had normal GPI transamidase activity.
      Taken together, there is an unknown gene required for efficient attachment of GPI
      to proteins.

PMID- 16102724
TI  - MCP-1/CCL2 protects cardiac myocytes from hypoxia-induced apoptosis by a
      G(alphai)-independent pathway.
AB  - Chemokines, in addition to their chemotactic properties, act upon resident cells
      within a tissue and mediate other cellular functions. In a previous study, we
      demonstrated that CCL2 protects cultured mouse neonatal cardiac myocytes from
      hypoxia-induced cell death. Leukocyte chemotaxis has been shown to contribute to
      ischemic injury. While the chemoattractant properties of CCL2 have been
      established, the protective effects of this chemokine suggest a novel role for
      CCL2 in myocardial ischemia/reperfusion injury. The present study examined the
      cellular signaling pathways that promote this protection. Treatment of cardiac
      myocyte cultures with CCL2 protected them from hypoxia-induced apoptosis. This
      protection was not mediated through the activation of G(alphai) signaling that
      mediates monocyte chemotaxis. Inhibition of the ERK1/2 signaling pathway
      abrogated CCL2 protection. Caspase 3 activation and JNK/SAPK phosphorylation were
      decreased in hypoxic myocytes co-treated with CCL2 as compared to hypoxia only
      treated cultures. Expression of the Bcl-2 family proteins, Bcl-xL and Bag-1, was
      increased in CCL2-treated myocytes subjected to hypoxia. There was also
      downregulation of Bax protein levels as a result of CCL2 co-treatment. These data
      suggest that CCL2 cytoprotection and chemotaxis may occur through distinct
      signaling mechanisms.

PMID- 16102725
TI  - Curcumin suppresses phorbol ester-induced matrix metalloproteinase-9 expression
      by inhibiting the PKC to MAPK signaling pathways in human astroglioma cells.
AB  - The aberrant expression of matrix metalloproteinase-9 (MMP-9) is implicated in
      the invasion and angiogenesis process of brain tumor. This study has investigated
      the effects of curcumin on MMP-9 expression in human astroglioma cell lines.
      Curcumin significantly inhibited the MMP-9 enzymatic activity and protein
      expression that was induced by PMA. The inhibitory effect of curcumin on MMP-9
      expression correlates with the decreased MMP-9 mRNA level and the suppression of
      MMP-9 promoter activity. The curcumin-mediated inhibition of MMP-9 gene
      expression appears to occur via NF-kappaB and AP-1 because their DNA binding
      activities were suppressed by curcumin. Furthermore, curcumin strongly repressed
      the PMA-induced phosphorylation of ERK, JNK, and p38 MAP kinase, which were
      dependent on the PKC pathway. Therefore, the inhibition of MMP-9 expression by
      curcumin might have therapeutic potential for controlling the growth and
      invasiveness of brain tumor.

PMID- 16102726
TI  - PBT-3, a hepoxilin stable analog, causes long term inhibition of growth of K562
      solid tumours in vivo.
AB  - We demonstrate herein that daily administration of PBT-3 for 8 days to NU/NU mice
      bearing solid tumours derived from the s.c. administration of the leukemic cell
      line K562 results in inhibition of growth of the tumours in vivo, and this
      inhibition lasts for 60 days after stopping treatment with PBT-3 before recovery
      of tumour growth is re-established. Similar findings were observed when the mice
      were treated with Gleevec (STI-571). These results provide new evidence that PBT
      3 is effective in controlling solid tumour growth in vivo and suggest that the
      PBT family may be useful in the development of new drugs in cancer therapy.

PMID- 16102727
TI  - Involvement of the collagen I-binding motif in the anti-angiogenic activity of
      pigment epithelium-derived factor.
AB  - Pigment epithelium-derived factor (PEDF) is the most potent endogenous inhibitor
      of angiogenesis in age-related macular degeneration and tumors. However, the
      molecular mechanism of the anti-angiogenic activity of PEDF is poorly understood.
      PEDF interacts with the extracellular matrix (ECM) in vitro. Here, we
      investigated the possible involvement of the motif for ECM interaction in the
      anti-angiogenic activity of PEDF. The growth rates of HeLa cells in culture were
      not affected by transfection of PEDF, indicating that PEDF did not suppress tumor
      cell growth directly. In tumor xenografts, the overexpression of wild-type PEDF
      significantly suppressed tumor growth, whereas a mutant of the collagen I-binding
      site of PEDF (Col-mut PEDF) did not inhibit tumor growth. A mutant of the heparin
      binding site of PEDF (Hep-mut PEDF) suppressed tumor growth. Histological
      analysis showed that the density and area of microvasculatures in either PEDF or
      Hep-mut PEDF were suppressed when compared with those in either vector or Col-mut
      PEDF. Our data indicate that PEDF inhibits tumor growth via its anti-angiogenic
      activity, and the collagen I-binding motif of PEDF is involved in the biological
      activity.

PMID- 16102728
TI  - Negative regulation of beta-catenin/Tcf signaling by naringenin in AGS gastric
      cancer cell.
AB  - Functional activation of beta-catenin/Tcf signaling plays an important role in
      early events in carcinogenesis. We examined the effect of naringenin against beta
      catenin/Tcf signaling in gastric cancer cells. Reporter gene assay showed that
      naringenin inhibited beta-catenin/Tcf signaling efficiently. In addition, the
      inhibition of beta-catenin/Tcf signaling by naringenin in HEK293 cells
      transiently transfected with constitutively mutant beta-catenin gene, whose
      product is not phosphorylated by GSK3beta, indicates that its inhibitory
      mechanism was related to beta-catenin itself or downstream components. To
      investigate the precise inhibitory mechanism, we performed immunofluorescence,
      Western blot, and EMSA. As a result, our data revealed that the beta-catenin
      distribution and the levels of nuclear beta-catenin and Tcf-4 proteins were
      unchanged after naringenin treatment. Moreover, the binding activities of Tcf
      complexes to consensus DNA were not affected by naringenin. Taken together, these
      data suggest that naringenin inhibits beta-catenin/Tcf signaling in gastric
      cancer with unknown mechanisms.

PMID- 16102729
TI  - A practical guide to mitochondrial DNA error prevention in clinical, forensic,
      and population genetics.
AB  - Several suggestions have been made for avoiding errors in mitochondrial DNA
      (mtDNA) sequencing and documentation. Unfortunately, the current clinical,
      forensic, and population genetic literature on mtDNA still delivers a large
      number of studies with flawed sequence data, which, in extreme cases, damage the
      whole message of a study. The phylogenetic approach has been shown to be useful
      for pinpointing most of the errors. However, many geneticists, especially in the
      forensic and medical fields, are not familiar with either effective search
      strategies or the evolutionary terminology. We here provide a manual that should
      help prevent errors at any stage by re-examining data fresh from the sequencer in
      the light of previously published data. A fictitious case study of a European
      mtDNA data set (albeit composed from the literature) then demonstrates the steps
      one has to go through in order to assess the quality of sequencing and
      documentation.

PMID- 16102730
TI  - Rapid synthesis of DNA-cysteine conjugates for expressed protein ligation.
AB  - We report a rapid method for the covalent modification of commercially available
      amino-modified DNA oligonucleotides with a cysteine moiety. The resulting DNA
      cysteine conjugates are versatile reagents for the efficient preparation of
      covalent DNA-protein conjugates by means of expressed protein ligation (EPL). The
      EPL method allows for the site-specific coupling of cysteine-modified DNA
      oligomers with recombinant intein-fusion proteins, the latter of which contain a
      C-terminal thioester enabling the mild and highly specific reaction with N
      terminal cysteine compounds. We prepared a cysteine-modifier reagent in a single
      step reaction which allows for the rapid and near quantitative synthesis of
      cysteine-DNA conjugates. The latter were ligated with the green fluorescent
      protein mutant EYFP, recombinantly expressed as an intein-fusion protein,
      allowing for the mild and selective formation of EYFP-DNA conjugates in high
      yields of about 60%. We anticipate many applications of our approach, ranging
      from protein microarrays to the arising field of nanobiotechnology.

PMID- 16102731
TI  - A high-affinity monoclonal antibody with functional activity against the 5
      hydroxytryptaminergic (5-HT4) receptor.
AB  - Splenocytes from a BALB/c mouse immunised with a synthetic peptide corresponding
      to the second extracellular loop of the 5-HT4 receptor were fused with SP2/O
      myeloma cells to produce a monoclonal antibody. The monoclonal antibody was of
      the IgG2b isotype. The antibody recognised the human 5-HT4(g) (h5-HT4(g))
      receptor by immunoblots and by immunofluorescence on chinese hamster ovary (CHO)
      cells expressing this 5-HT4 receptor isoform. Epitope mapping of the antibody
      suggested the recognition of a conformational epitope, encompassing the N- and C
      terminal fragments of the second extracellular loop. Kinetic experiments using
      surface plasmon resonance showed that the antibody had a picomolar affinity for
      its cognate peptide. Inhibition experiments using the same methodology confirmed
      the specificity of the interaction. The antibody at a concentration of 500 pM
      competitively inhibited inverse agonist GR113808 binding and showed an inverse
      agonist effect on the basal activity of CHO cells expressing the 5-HT4(g)
      receptor. The antibody decreased the effect of 5-HT at 500 and 50 pM
      concentrations but it increased 5-HT-induced cAMP levels at 5 pM. The dual effect
      of the monoclonal antibody could be ascribed to mono- or bivalent recognition of
      the receptor. The antibody described here is the first example of a high-affinity
      modulator of the 5-HT4 receptor.

PMID- 16102732
TI  - Inhibitory effects of rosmarinic acid on adriamycin-induced apoptosis in H9c2
      cardiac muscle cells by inhibiting reactive oxygen species and the activations of
      c-Jun N-terminal kinase and extracellular signal-regulated kinase.
AB  - Rosmarinic acid (RA) is a naturally occurring polyphenolic and is found in
      several herbs in the Lamiaceae family, such as, Perilla frutescens. ADR is a
      potent anti-tumor drug, but is unfortunately potently cardiotoxic. This study was
      undertaken to investigate the inhibitory effect of RA on ADR-induced apoptosis in
      H9c2 cardiac muscle cells at a mechanistic level. In vitro, ADR significantly
      decreased the viabilities of H9c2 cells, and this was accompanied by apoptotic
      features, such as a change in nuclear morphology and caspase protease activation.
      RA was found to markedly inhibit these apoptotic characteristics by reducing
      intracellular ROS generation and by recovering the mitochondria membrane
      potential (delta psi). In addition, RA reversed the downregulations of GSH, SOD
      and Bcl-2 by ADR. In the present study, ADR was found to activate c-Jun N
      terminal kinase (JNK) and extracellular signal-regulated kinase (ERK),
      transcriptional factor-activator-protein (AP)-1. We found that c-fos, Jun-B, Jun
      D and p-c-Jun were super shifted by ADR, indicating that these proteins have an
      important role in the ADR-induced AP-1 activation. The inhibitions of JNK and ERK
      using appropriate inhibitors or dominant negative cell lines reduced ADR-induced
      apoptosis in H9c2 cardiac muscle cells. Taken together, these results suggest
      that RA can inhibit ADR-induced apoptosis in H9C2 cardiac muscle cells by
      inhibiting ROS generation and JNK and ERK activation. Thus, we propose that RA
      should be viewed as a potential chemotherapeutic that inhibits cardiotoxicity in
      ADR-exposed patients.

PMID- 16102733
TI  - Resveratrol inhibits type II phosphatidylinositol 4-kinase: a key component in
      pathways of phosphoinositide turn over.
AB  - Resveratrol has anti-inflammatory, cardio protective and cancer chemopreventive
      properties. The molecular targets for resveratrol in early signaling cascades are
      not well understood. Resveratrol inhibits type II PtdIns 4-kinase but not PtdIns
      3-kinase activity in vitro. Resveratrol directly binds to the enzyme with a Kd of
      7.2 microM. Kinetic studies show that resveratrol competes with PtdIns binding.
      Inhibition of PtdIns 4-kinase activity by resveratrol/phenylarsine oxide reduces
      Jurkat cell adhesion to matrigel/fibronectin coated surfaces, suggesting a role
      for type II PtdIns 4-kinase in lymphocyte infiltration to the sites of
      inflammation.

PMID- 16102734
TI  - Peptide inhibitors of G protein-coupled receptor kinases.
AB  - G protein-coupled receptor kinases (GRKs) are regulatory enzymes involved in the
      modulation of seven-transmembrane-helix receptors. In order to develop specific
      inhibitors for these kinases, we synthesized and investigated peptide inhibitors
      derived from the sequence of the first intracellular loop of the beta2-adrenergic
      receptor. Introduction of changes in the sequence and truncation of N- and C
      terminal amino acids increased the inhibitory potency by a factor of 40. These
      inhibitors not only inhibited the prototypical GRK2 but also GRK3 and GRK5. In
      contrast there was no inhibition of protein kinase C and protein kinase A even at
      the highest concentration tested. The peptide with the sequence AKFERLQTVTNYFITSE
      inhibited GRK2 with an IC50 of 0.6 microM, GRK3 with 2.6 microM and GRK5 with 1.6
      microM. The peptide inhibitors were non-competitive for receptor and ATP. These
      findings demonstrate that specific peptides can inhibit GRKs in the submicromolar
      range and suggest that a further decrease in size is possible without losing the
      inhibitory potency.

PMID- 16102735
TI  - NOS-positive local circuit neurons are exclusively axo-dendritic cells both in
      the neo- and archi-cortex of the rat brain.
AB  - Neuronal nitric oxide synthase (nNOS)-containing neurons and axon terminals were
      examined in the rat somatosensory and temporal neocortex, in the CA3/a-c areas of
      Ammon's horn and in the hippocampal dentate gyrus. In these areas, only
      nonpyramidal neurons were labeled with the antibody against nNOS. Previous
      observations suggested that all nNOS-positive nonpyramidal cells are GABAergic
      local circuit neurons, which form exclusively symmetric synapses. In agreement
      with this, nNOS-positive axon terminals in the hippocampal formation formed
      symmetric synapses exclusively with dendritic shafts. In the neocortex, in
      contrast, in addition to the nNOS-positive axon terminals that formed synapses
      with unlabeled spiny and aspiny dendrites and with nNOS-positive aspiny
      dendrites, a small proportion of the nNOS-positive axon terminals formed
      symmetric synapses with dendritic spines. These results suggest that nNOS
      positive local circuit neurons form a distinct group of axo-dendritic cells
      displaying slightly different domain specificity in the archi- and neocortex.
      However, nNOS-positive cells show no target selectivity, because they innervate
      principal cells and local circuit neurons. Afferents to the NOS-positive cells
      display neither domain nor target selectivity, because small unlabeled terminals
      formed synapses with both the soma or dendrites of nNOS-positive neurons and an
      adjacent unlabeled dendrite or spine in both the hippocampal formation and in
      neocortex.

PMID- 16102736
TI  - Effects and mechanisms of supraspinal administration of rat/mouse hemokinin-1, a
      mammalian tachykinin peptide, on nociception in mice.
AB  - Rat/mouse hemokinin 1 (r/m HK-1) is a novel tachykinin peptide whose biological
      functions are not fully understood. This work was designed to observe the effects
      of r/m HK-1 in pain modulation at supraspinal level in mice using tail-flick
      test. Intracerebroventricular (i.c.v.) administration of r/m HK-1 (0.1, 0.3, 1, 3
      nmol/mouse) dose-dependently induced potent analgesic effect (ED(50) = 0.2877
      nmol/mouse). When r/m HK-1 co-injected (i.c.v.) with SR140333 (a selective NK(1)
      receptor antagonist), SR140333 could fully antagonize the analgesic effect of r/m
      HK-1. The maximal analgesic effect of r/m HK-1 (3 nmol/mouse) could also be
      reversed by naloxone (i.p., 2 mg/kg). However, i.c.v. low dose administration of
      r/m HK-1 (10, 3, 1 pmol/mouse) induced hyperalgesia with a "U" shape curve, which
      means that the maximal hyperalgesic effect appeared at 3 pmol/mouse, and this
      effect of r/m HK-1 could also be fully blocked by SR140333. Interestingly,
      [Nphe(1)]NC(1-13)NH(2), a selective opioid receptor like-1 (ORL-1) receptor
      antagonist, could fully reverse the maximal hyperalgesic effect of r/m HK-1 (3
      pmol/mouse). In addition, when r/m HK-1 co-injected (i.c.v.) with SR48968 (a
      selective NK(2) receptor antagonist), SR48968 could hardly affect the nociceptive
      effects of r/m HK-1 either at nanomole concentration or at picomole
      concentration. These findings suggested that r/m HK-1 might play an important
      role in pain modulation at supraspinal level in mice and these effects were first
      elicited through the activation of NK(1) receptor, subsequently, whether
      activation of the classical opioid receptor or the ORL1 receptor depending on the
      dose of i.c.v. administration of r/m HK-1.

PMID- 16102737
TI  - Morphine has an antinociceptive effect through activation of the okadaic-acid
      sensitive Ser/Thr protein phosphatases PP 2 A and PP5 estimated by tail-pinch
      test in mice.
AB  - Although the serine/threonine protein kinases involved in the pharmacological
      action of morphine are well recognized, the critical contribution of
      serine/threonine protein phosphatase (PP) has been appreciated on to a slight
      degree. We examined the involvement of subtypes of serine/threonine protein
      phosphatase (PP) in the antinociceptive effect of morphine in mice. The
      antinociceptive effect of subcutaneously administered morphine was attenuated by
      simultaneously intracerebroventricular (i.c.v.) or intrathecal (i.t.) injection
      of okadaic acid (OA), a PP inhibitor. To reveal which subtypes of PPs
      participated in the antinociceptive effect of morphine, mice received i.c.v. or
      i.t. injections of antisense oligodeoxynucleotide (AS-ODN) directed against
      either the PP 2 A or PP5 subtypes of PPs before assessment of morphine-induced
      antinociception. Pretreatment with AS-ODN against PP 2 A or PP5 via each route
      weakened the antinociceptive effect of morphine, accompanied by reduction of
      expression levels of PP in the periaqueductal gray (PAG) and the spinal cord.
      Subcutaneously administered morphine increased activity of OA-sensitive PPs in
      the PAG and the spinal cord in a dose-dependent manner; this was prevented by
      concurrent administration of naloxone. These results suggest that PP 2 A and PP5
      are involved in the antinociceptive effect of morphine in mice.

PMID- 16102738
TI  - Present and future of rapid and/or high-throughput methods for nucleic acid
      testing.
AB  - BACKGROUND: Behind the success of 'completing' the human genome project was a
      more than 30-year history of technical innovations for nucleic acid testing.
      METHODS: Discovery of specific restriction endonucleases and reverse
      transcriptase was followed shortly by the development of the first diagnostic
      nucleic acid tests in the early 1970s. Introduction of Southern, Northern and dot
      blotting and DNA sequencing later in the 1970s considerably advanced the
      diagnostic capabilities. Nevertheless, it was the discovery of the polymerase
      chain reaction (PCR) in 1985 that led to an exponential growth in molecular
      biology and the introduction of practicable nucleic acid tests in the routine
      laboratory. The past two decades witnessed a continuing explosion of
      technological innovations in molecular diagnostics. In addition to classic PCR
      and reverse transcriptase PCR, numerous variations of PCR and alternative
      amplification techniques along with an ever-increasing variety of detection
      chemistries, closed tube (homogeneous) assays, and automated systems were
      developed. Discovery of real-time quantitative PCR and the development of
      oligonucleotide microarrays, the 'DNA chip', in the 1990s heralded the beginning
      of another revolution in molecular biology and diagnostics that is still in
      progress.

PMID- 16102739
TI  - Towards a nucleic acid-based diagnosis in clinical parasitology and mycology.
AB  - BACKGROUND: Multiple in-house polymerase chain reaction (PCR) assays for the
      diagnosis of parasitic and fungal diseases have been reported. Encouraging
      results have been published to anticipate or improve the diagnosis. However, the
      absence of standardized methods has led to discrepant results. As a consequence,
      these tests are not recognized as consensual diagnostic criteria. METHODS: The
      major breakthrough for improving the results of these methods is the emergence of
      real-time technologies. This markedly improves the reliability of the PCR results
      by dramatically decreasing the risk of false positive results due to PCR products
      carryover. Moreover, the quantitative results provided by these techniques allow
      to compare rapidly the efficiency of primers, probes, and DNA extraction.
      Therefore, one can expect a more consensual method to implement comparisons
      between laboratories. Automated DNA extraction should also be useful to achieve
      this goal. Whatever sophisticated technology is used, the meaning of detecting
      nucleic acids in a given clinical sample still needs to be defined. This requires
      well-designed studies with clinical consensual criteria and PCR techniques that
      are as similar as possible. CONCLUSIONS: The development of real-time technology
      should improve our knowledge in order to give the clinicians informative clues
      for decision-making.

PMID- 16102740
TI  - Applications of Luminex xMAP technology for rapid, high-throughput multiplexed
      nucleic acid detection.
AB  - BACKGROUND: As we enter the post-genome sequencing era and begin to sift through
      the enormous amount of genetic information now available, the need for
      technologies that allow rapid, cost-effective, high-throughput detection of
      specific nucleic acid sequences becomes apparent. Multiplexing technologies,
      which allow for simultaneous detection of multiple nucleic acid sequences in a
      single reaction, can greatly reduce the time, cost and labor associated with
      single reaction detection technologies. METHODS: The Luminex xMAP system is a
      multiplexed microsphere-based suspension array platform capable of analyzing and
      reporting up to 100 different reactions in a single reaction vessel. This
      technology provides a new platform for high-throughput nucleic acid detection and
      is being utilized with increasing frequency. Here we review specific applications
      of xMAP technology for nucleic acid detection in the areas of single nucleotide
      polymorphism (SNP) genotyping, genetic disease screening, gene expression
      profiling, HLA DNA typing and microbial detection. CONCLUSIONS: These studies
      demonstrate the speed, efficiency and utility of xMAP technology for
      simultaneous, rapid, sensitive and specific nucleic acid detection, and its
      capability to meet the current and future requirements of the molecular
      laboratory for high-throughput nucleic acid detection.

PMID- 16102741
TI  - Clinical genotyping: the need for interrogation of single nucleotide
      polymorphisms and mutations in the clinical laboratory.
AB  - BACKGROUND: Detection of single nucleotide polymorphisms (SNPs) and gene
      mutations is becoming more routine to the clinical laboratory. METHODS:
      Completion of the Human Genome Project has led to new scientific knowledge of
      human disease processes that has revealed the most fundamental of abnormalities
      in nucleic acids while at the same time bringing some of the most sophisticated
      diagnostic tools to the clinical laboratory. In addition, public awareness (both
      lay persons and healthcare providers) and sensitivity to human genetics has
      increased tremendously. Together, this rapidly evolving science and increased
      public education has led to an increasing demand for genotypic testing.
      CONCLUSIONS: There are several clinical applications of human genotyping that are
      available using these newer technologies.

PMID- 16102742
TI  - Ice-active proteins from the Antarctic nematode Panagrolaimus davidi.
AB  - The Antarctic nematode Panagrolaimus davidi has an ice-active protein that shows
      recrystallization inhibition but no thermal hysteresis. It belongs to a class of
      ice-active proteins found in a variety of freezing-tolerant organisms that
      display insignificant levels of thermal hysteresis in the context of the
      environmental temperatures to which they are exposed. The recrystallization
      inhibition activity of the P. davidi ice-active protein is present at low
      concentrations, is relatively heat stable, is affected more by acid than by
      alkaline pH, is not calcium dependant and is not affected by reagents that target
      carbohydrate residues or sulphydryl linkages. A hexagonal ice crystal growth form
      also indicates the presence of an ice-active protein. This protein could have
      important functions in the survival of intracellular freezing by this organism by
      controlling the stability of ice after its formation.

PMID- 16102743
TI  - Dynamic and sequential patterning of the zebrafish posterior hindbrain by
      retinoic acid.
AB  - A prominent region of the vertebrate hindbrain is subdivided along the anterior
      posterior axis into a series of seven segments, or rhombomeres. The identity of
      each rhombomere is specified by the expression of conserved transcription
      factors, including Krox-20, vHnf1, Val (Kreisler, Mafb) and several Hox proteins.
      Previous work has shown that retinoic acid (RA) signaling plays a critical role
      in regulating the expression of these factors and that more posterior rhombomeres
      require higher levels of RA than more anterior rhombomeres. Models to account for
      RA concentration dependency have proposed either a static RA gradient or
      increasing time periods of RA exposure. Here, we provide evidence against both of
      these models. We show that early zebrafish rhombomere-specification genes,
      including vhnf1 in r5-r6 and hoxd4a in r7, initiate expression sequentially in
      the hindbrain, each adjacent to the source of RA synthesis in paraxial mesoderm.
      By knocking down RA signaling, we show that progressively more posterior
      rhombomeres require increasingly higher levels of RA signaling, and vhnf1 and
      hoxd4a expression are particularly RA-dependent. RA synthesis is required just at
      the time of initiation, but not for maintenance, of vhnf1 and hoxd4a expression.
      Furthermore, a premature RA increase causes premature activation of vhnf1 and
      hoxd4a expression. Our results support a new model of dynamic RA action in the
      hindbrain, in which a temporally increasing source of RA is required to
      sequentially initiate progressively more posterior rhombomere identities.

PMID- 16102744
TI  - Neuromuscular synaptogenesis in wild-type and mutant zebrafish.
AB  - Genetic screens for synaptogenesis mutants have been performed in many organisms,
      but few if any have simultaneously screened for defects in pre- and postsynaptic
      specializations. Here, we report the results of a small-scale genetic screen, the
      first in vertebrates, for defects in synaptogenesis. Using zebrafish as a model
      system, we identified seven mutants that affect different aspects of
      neuromuscular synapse formation. Many of these mutant phenotypes have not been
      previously reported in zebrafish and are distinct from those described in other
      organisms. Characterization of mutant and wild-type zebrafish, from the time that
      motor axons first arrive at target muscles through adulthood, has provided the
      new information about the cellular events that occur during neuromuscular
      synaptogenesis. These include insights into the formation and dispersal of
      prepatterned AChR clusters, the relationship between motor axon elongation and
      synapse size, and the development of precise appositions between presynaptic
      clusters of synaptic vesicles in nerve terminals and postsynaptic receptor
      clusters. In addition, we show that the mechanisms underlying synapse formation
      within the myotomal muscle itself are largely independent of those that underlie
      synapse formation at myotendinous junctions and that the outgrowth of secondary
      motor axons requires at least one cue not necessary for the outgrowth of primary
      motor axons, while other cues are required for both. One-third of the mutants
      identified in this screen did not have impaired motility, suggesting that many
      genes involved in neuromuscular synaptogenesis were missed in large scale
      motility-based screens. Identification of the underlying genetic defects in these
      mutants will extend our understanding of the cellular and molecular mechanisms
      that underlie the formation and function of neuromuscular and other synapses.

PMID- 16102745
TI  - The duality of beta-catenin function: a requirement in lens morphogenesis and
      signaling suppression of lens fate in periocular ectoderm.
AB  - In the current analysis, we have investigated both the cytoskeletal and signaling
      roles of beta-catenin during the early phases of lens development using
      conditional loss- and gain-of-function strategies. Conditional loss of beta
      catenin in the presumptive lens does not perturb the normal sequential appearance
      of lens fate markers but results in a dramatic failure of the coordinated
      epithelial cell behavior that constitutes lens morphogenesis. Similarly, loss-of
      function for Lrp6, the Wnt pathway coreceptor expressed in the eye primordium,
      does not prevent expression of lens induction markers. Surprisingly, conditional
      deletion of beta-catenin in periocular ectoderm results in the formation of Prox
      1 and beta-crystallin-positive ectopic lentoid bodies. Combined with the
      observation that the Wnt pathway reporter TOPGAL is expressed in nasal periocular
      ectoderm, these data suggest that, in this location, the canonical Wnt signaling
      pathway normally suppresses lens fate in favor of other structures. Consistent
      with this proposal, a dominant-active form of beta-catenin causes a loss of lens
      fate and a complete absence of lens development when expressed in the presumptive
      lens ectoderm.

PMID- 16102746
TI  - Organization of the pronephric filtration apparatus in zebrafish requires
      Nephrin, Podocin and the FERM domain protein Mosaic eyes.
AB  - Podocytes are specialized cells of the kidney that form the blood filtration
      barrier in the kidney glomerulus. The barrier function of podocytes depends upon
      the development of specialized cell-cell adhesion complexes called slit
      diaphragms that form between podocyte foot processes surrounding glomerular blood
      vessels. Failure of the slit-diaphragm to form results in leakage of high
      molecular weight proteins into the blood filtrate and urine, a condition called
      proteinuria. In this work, we test whether the zebrafish pronephros can be used
      as an assay system for the development of glomerular function with the goal of
      identifying novel components of the slit-diaphragm. We first characterized the
      function of the zebrafish homolog of Nephrin, the disease gene associated with
      the congenital nephritic syndrome of the Finnish type, and Podocin, the gene
      mutated in autosomal recessive steroid-resistant nephrotic syndrome. Zebrafish
      nephrin and podocin were specifically expressed in pronephric podocytes and
      required for the development of pronephric podocyte cell structure.
      Ultrastructurally, disruption of nephrin or podocin expression resulted in a loss
      of slit-diaphragms at 72 and 96 h post-fertilization and failure to form normal
      podocyte foot processes. We also find that expression of the band 4.1/FERM domain
      gene mosaic eyes in podocytes is required for proper formation of slit-diaphragm
      cell-cell junctions. A functional assay of glomerular filtration barrier revealed
      that absence of normal nephrin, podocin or mosaic eyes expression results in loss
      of glomerular filtration discrimination and aberrant passage of high molecular
      weight substances into the glomerular filtrate.

PMID- 16102747
TI  - Transient lower esophageal sphincter relaxations in dogs are inhibited by a
      metabotropic glutamate receptor 5 antagonist.
AB  - Transient lower esophageal sphincter relaxation is the major mechanism for
      gastroesophageal reflux. The present study was initiated to investigate the
      potential effect of the metabotropic glutamate 5 (mGlu5) receptor antagonist, 2
      methyl-6-(phenylethynyl)-pyridine (MPEP), on transient lower esophageal sphincter
      relaxations in the conscious dog. MPEP (1.4-8.7 micromol/kg i.v.) produced a dose
      dependent inhibition of transient lower esophageal sphincter relaxations (59+/
      11% inhibition at 8.7 micromol/kg). In addition, there was a reduction of the
      number of reflux episodes and an increase in latency time to the occurrence of
      the first transient lower esophageal sphincter relaxation. No effect was seen on
      basal lower esophageal sphincter pressure or on swallowing. It is concluded that
      the mGlu5 receptor antagonist MPEP potently inhibits transient lower esophageal
      sphincter relaxations and that the mGlu5 receptor is a potential target for
      treatment of gastroesophageal reflux disease.

PMID- 16102748
TI  - The red wine polyphenol, resveratrol, exerts acute direct actions on guinea-pig
      ventricular myocytes.
AB  - Epidemiological evidence suggests that moderate consumption of red wine may be
      cardioprotective, although the precise mechanism(s) responsible remains poorly
      understood. We hypothesized that the red wine polyphenol, resveratrol, may exert
      direct actions on the heart and thus potentially contribute to cardioprotection.
      We show that resveratrol acutely decreases Ca2+ transient amplitude in isolated
      cardiac myocytes. Intriguingly, resveratrol simultaneously increases cell
      shortening in half the cells tested, while decreasing shortening in the other
      half. The former could be attributed to heightened myofilament Ca2+ sensitivity.
      This was no longer observed in myocytes that had been incubated with the
      oestrogen receptor antagonist, ICI 182,780, suggesting an oestrogen-receptor
      dependent mechanism of action. In addition, resveratrol significantly decreased
      action potential duration and the peak L-type Ca2+ current. Our findings provide
      evidence that resveratrol exerts multiple direct actions on cardiac myocytes, the
      net result of which is no overall change in cell contraction. The clinical
      significance of these results remains to be determined.

PMID- 16102749
TI  - Cytoprotective effect of tectorigenin, a metabolite formed by transformation of
      tectoridin by intestinal microflora, on oxidative stress induced by hydrogen
      peroxide.
AB  - In the present study, the antioxidative properties of tectorigenin, a metabolite
      formed by transformation of tectoridin by intestinal microflora, were
      investigated. Tectorigenin was found to scavenge intracellular reactive oxygen
      species, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and thus prevented
      lipid peroxidation. The radical scavenging activity of tectorigenin protected the
      viability of Chinese hamster lung fibroblast (V79-4) cells exposed to hydrogen
      peroxide (H2O2) via activation of extracellular signal regulated kinase (ERK)
      pathway. Furthermore, tectorigenin reduced the apoptotic cells formation and cell
      cycle arrest at G2/M phase induced by H2O2. Tectorigenin increased the activities
      of cellular antioxidant enzymes like superoxide dismutase, catalase, glutathione
      peroxidase, and also increased their protein level. Taken together, these
      findings suggest that tectorigenin protected V79-4 cells against H2O2 damage, by
      enhancing the antioxidative activity and by activating ERK pathway.

PMID- 16102750
TI  - Effect of taurine and apical potassium concentration on electrophysiologic
      parameters of bovine retinal pigment epithelium.
AB  - The purpose of this study was to assess the effect of taurine and apical
      potassium concentration modelling in vivo light evoked changes on the
      transepithelial potential (TEP) and the transepithelial resistance (TER) of
      isolated bovine retinal pigment epithelium (RPE). Isolated specimens of bovine
      non-tapetal RPE-Bruch's-choroid (RPE-BC) were mounted in modified Ussing
      chambers. The apical and the basolateral side of the preparations were exposed to
      10 mm and 10 microm concentrations of taurine in Krebs' medium with either 6.04
      or 2.2 mm potassium in the apical compartment. TEP and TER were recorded over 140
      min. TEP and TER decreased with exposure to taurine over the course of 1 hr
      followed by a stabilisation. The degree of this response did not depend on the
      concentration of taurine but was more pronounced when taurine was added to the
      apical compartment. Lowering apical potassium from 6.04 to 2.2 mm further
      pronounced the decrease of TEP and TER. The data show that light-induced release
      of taurine from the outer retina and light-induced decrease of the potassium
      concentration in the subretinal space synergistically lead to a temporary
      decrease in TEP and TER. Thereby, taurine uptake into the RPE is reduced probably
      by a reduction of the activity of the electrogenic Na+/taurine co-transporter of
      the apical RPE cell membrane. The findings suggest a mechanism whereby the
      sustained presence of taurine in the interphotoreceptor matrix following exposure
      to light may protect photoreceptor outer segments from light-induced oxidative
      stress.

PMID- 16102751
TI  - Genetic background determines susceptibility to experimental immune-mediated
      blepharoconjunctivitis: comparison of Balb/c and C57BL/6 mice.
AB  - Balb/c and C57BL/6 mice have been reported to be biased towards Th2 and Th1
      immune responses, respectively. We investigated which strain is more susceptible
      to the development of experimental immune-mediated blepharoconjunctivitis (EC),
      which is predominantly mediated by Th2 immune responses. EC was induced by three
      different methods in Balb/c and C57BL/6 mice using ragweed (RW) as the antigen.
      The mice were thus either actively immunized with RW, passively immunized by
      transfer of RW-primed T cells, or passively immunized by transfer of RW-specific
      IgE, followed by RW challenge in eye drops. Twenty-four hours after the
      challenge, conjunctivas, sera and spleens were harvested for histological
      analysis, measurement of serum IgE and assessment of cellular immune responses,
      respectively. The responses of the Balb/c and C57BL/6 mice were compared. In
      addition, to assess the involvement of IFN-gamma in the development of EC in the
      two strains, IFN-gamma knockout (GKO) mice of the two strains were actively
      immunized and evaluated as above. Regardless of the method of induction, EC, as
      determined by the degree of eosinophil infiltration into the conjunctiva, was
      more severe in Balb/c mice than in C57BL/6 mice. Moreover, more IgE was produced
      by actively immunized Balb/c mice than C57BL/6 mice and RW-primed splenocytes
      from Balb/c mice produced more IL-4 but less IFN-gamma than those from C57BL/6
      mice. EC could be induced in the GKO mice of both strains. However, when their EC
      was compared to that in WT mice, significantly less infiltration of eosinophils
      was noted in the Balb/c GKO mice. Taken together, Balb/c mice are more
      susceptible to EC than C57BL/6 mice and this higher susceptibility might be
      related to the Th2 immune response bias of Balb/c mice. Furthermore, the
      involvement of endogenous IFN-gamma in the development of EC in these two strains
      differs.

PMID- 16102752
TI  - Modulating furin activity with designed mini-PDX peptides: synthesis and in vitro
      kinetic evaluation.
AB  - A peptide was designed from reactive site loop structure of alpha1 Antitrypsin
      Portland known as alpha1 PDX as a novel mini-PDX inhibitor of furin. The sequence
      was derived from (367-394) that contains the crucial furin cleavage motif
      RIPR382. A P3 mutant replacing Ile380 by Leu was prepared as a first model
      peptide. A Cys residue was inserted at each terminal of the peptide for purpose
      of cyclisation which was accomplished by air or iodine-induced oxidation. This
      mini-PDX peptide both cyclic and acyclic form inhibited in vitro furin activity
      (IC50 in nM) when measured against either substrates Boc-RVRRdown double arrow
      MCA or QVEGF-C [Abz-QVHSIIRRdown double arrow SLP-Y(NO2)-A-CONH2, Abz=2-amino
      benzoic acid and Y(NO2)=3-nitro tyrosine], latter being derived from vascular
      endothelial growth factor-C (VEGF-C) processing site. The geometrically
      constrained structure mimicking PDX reactive loop is crucial for enzyme
      inhibition. Our study further revealed that both mini-PDX peptides inactivate
      furin in a slow tight binding manner, with disulfide-bridged cyclic form being
      slightly more potent. Unlike PDX, these peptides inhibit furin via a different
      mechanistic pathway. The study provides an alternate strategy for development of
      efficient peptide-based inhibitors of Proprotein Convertases including furin.

PMID- 16102753
TI  - Alternative splicing of Slo channel gene programmed by estrogen, progesterone and
      pregnancy.
AB  - STREX alternative-exon adds to Slo channel a phosphorylation sequence that can
      invert protein kinase A (PKA) regulation from excitatory to inhibitory. Because
      pregnancy switches Slo responsiveness to PKA from inhibitory to excitatory, we
      hypothesized that STREX expression diminishes with pregnancy and is regulated by
      sex hormones. Different from total-rSlo, which is elevated around mid-pregnancy
      and decreases at term, STREX transcripts progressively decreased with pregnancy
      near 80% at term. STREX downregulation was mimicked by estrogen, and opposed by
      estrogen-receptor antagonist ICI 182,780 or progesterone (Pg). The regulation of
      STREX splicing directed by estrogen and Pg provides a mechanism for Slo's PKA
      related phenotypic alteration with pregnancy.

PMID- 16102755
TI  - Changes in steroidogenic enzyme and steroidogenic acute regulatory protein
      messenger RNAs in ovarian follicles during ovarian development of rainbow trout
      (Oncorhynchus mykiss).
AB  - In salmonid fishes, estradiol-17beta (E2) and 17alpha,20beta-dihydroxy-4-pregnen
      3-one (17,20beta-P) are the major steroid hormones controlling oocyte growth
      (vitellogenesis) and final maturation (resumption of meiosis). The aim of this
      study was to determine changes in mRNAs encoding ovarian steroidogenic enzymes
      and steroidogenic acute regulatory protein (StAR) during ovarian development in
      female rainbow trout. We analyzed the levels of mRNAs encoding the enzymes P450
      side-chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta
      HSD), 17alpha-hydroxylase/C17-C20 lyase (P450c17), aromatase (P450arom), and
      carbonyl reductase-like 20beta-hydroxysteroid dehydrogenase (20beta-HSD), and
      StAR in developing ovarian follicles of rainbow trout by Northern blot, in
      relation to the pattern of serum E2 and 17,20beta-P levels. Serum E2 levels were
      elevated during vitellogenesis and decreased prior to an ovulatory increase in
      17,20beta-P. Transcripts for P450scc and P450c17 increased in late vitellogenic
      follicles, then decreased in post-ovulatory follicles. In contrast, P450arom
      transcripts were abundant during vitellogenesis and then declined as
      vitellogenesis was completed and were barely detectable in post-ovulatory
      follicles. 3beta-HSD mRNA levels increased in late vitellogenic follicles and
      were maintained at high levels in post-ovulatory follicles. 20beta-HSD and StAR
      mRNA levels were very low during vitellogenesis, and then strongly increased
      during late vitellogenesis to a peak in post-ovulatory follicles. These results
      indicate that the expression of genes encoding steroidogenic enzymes and StAR
      change dynamically, dependent on the developmental stages of rainbow trout
      follicles. The acquisition of the ability of later stage follicles to rapidly
      produce large quantities of 17,20beta-P appears to be supported by a preparatory
      increase in mRNAs encoding StAR and other steroidogenic enzymes.

PMID- 16102754
TI  - Kruppel-like factor 5 promotes mitosis by activating the cyclin B1/Cdc2 complex
      during oncogenic Ras-mediated transformation.
AB  - We previously showed that the zinc finger-containing transcription factor Kruppel
      like factor 5 (KLF5) is important in mediating transformation by oncogenic H-Ras
      through induction of cyclin D1 expression and acceleration of the G1/S transition
      of the cell cycle. Here we present evidence of a role for KLF5 in accelerating
      mitotic entry in H-Ras-transformed NIH3T3 fibroblasts. When compared with non
      transformed parental NIH3T3 cells, H-Ras-transformed fibroblasts exhibit an
      increase in mitotic index, levels of cyclin B1 and Cdc2, and cyclin B1/Cdc2
      kinase activity. Inhibition of KLF5 expression in H-Ras-transformed cells with
      KLF5-specific small interfering RNA (siRNA) results in a decrease in each of the
      aforementioned parameters, with a concomitant reduction in the transforming
      potential of the cells. Conversely, over-expression of KLF5 in NIH3T3 cells leads
      to an increase in the promoter activity of the genes encoding cyclin B1 and Cdc2.
      These results indicate that KLF5 accelerates mitotic entry in H-Ras-transformed
      cells by transcriptionally activating cyclin B1 and Cdc2, which leads to an
      increase in cyclin B1/Cdc2 kinase activity. Extending our previous observation
      that KLF5 activates cyclin D1 transcription to promote G1/S transition, our
      current results further support a crucial function for KLF5 in mediating cellular
      transformation caused by oncogenic H-Ras.

PMID- 16102756
TI  - Effects of nutritional restrictions during post-hatching development on
      adrenocortical function in western scrub-jays (Aphelocoma californica).
AB  - Altricial birds grow rapidly during post-hatching period and are developmentally
      sensitive to variations in food supply. Limited food results in elevated
      corticosterone levels in chicks of semi-precocial birds but it is not clear
      whether altricial songbirds show similar adrenocortical stress response to
      nutritional restrictions during early development. It is also unknown how
      nutritional stress during early development affects the adrenocortical function
      later in life in altricial birds which show tremendous variation in the magnitude
      of adrenocortical stress response. Using western scrub-jays (Aphelocoma
      californica), we experimentally demonstrated that moderate food restrictions (65%
      of ad libitum) during post-hatching development caused significant elevation of
      baseline corticosterone levels in nest-bound chicks. Compared to controls, 1-year
      old scrub-jays that experienced nutritional deficits during post-hatching
      development also showed a marginally significant trend to have stronger
      adrenocortical stress response and significantly greater degree of fluctuating
      asymmetry in bone and feather measurements. Thus, our results demonstrated that
      developing altricial birds show adrenocortical response to nutritional deficits,
      which might produce long-term changes in responsiveness of the adrenal system.
      Our study suggests that baseline corticosterone levels are a good indicator of
      physiological conditions of developing birds and that individual variance in
      adrenocortical stress response commonly observed in many species might, at least
      in part, be explained by environmental conditions during early development.
      Considering that nutritional restrictions during early development are linked to
      many permanent changes including impaired cognitive abilities, corticosterone
      levels in developing young might be a reliable predictor of their future fitness.

PMID- 16102757
TI  - The adrenergic control of hepatic glucose and FFA metabolism in rainbow trout
      (Oncorhynchus mykiss): increased sensitivity to adrenergic stimulation with
      fasting.
AB  - The adrenergic control of glucose and FFA release was studied in hepatocytes of
      rainbow trout (Oncorhynchus mykiss), which were either normally fed or fasted for
      3 weeks. Isolated hepatocytes were incubated with adrenaline, noradrenaline, or
      isoprenaline (nonselective beta-agonist). Identification of the hepatic beta
      adrenoceptor was combined with quantification of the difference in its affinity
      for adrenaline and noradrenaline. To identify the beta-adrenoceptor subtype,
      isoprenaline incubations were combined with atenolol (selective beta(1)
      antagonist) or ICI 118,551 (selective beta2-antagonist). Stimulation of the beta
      adrenoceptor resulted in mobilisation of glucose, which was inhibited by ICI
      118,551 thus pointing to a beta2-subtype. The affinity of the beta2-adrenoceptor
      for isoprenaline and adrenaline (beta2-values of 8.3 and 7.9) was clearly higher
      than for noradrenaline (beta2-value of 6.5). This indicates that at physiological
      concentrations beta2-adrenoceptors in trout are mainly stimulated by adrenaline
      and not by noradrenaline. A significant effect of beta-adrenoceptor stimulation
      on the FFA release was also found, although only at high concentrations (i.e.,
      10(-6) and 10(-5)M). Again the beta2-adrenoceptor appeared to mediate the
      stimulation of hepatic FFA release. Upon fasting, both the basal glucose and FFA
      release were strongly decreased. The ratio between glucose and FFA release
      decreased from 15.4 to 4.3 upon fasting and at this ratio the energy output for
      both metabolites became equal. The mobilisation of FFA upon adrenergic
      stimulation was relatively conserved, namely -35% upon fasting, as opposed to 
      89% in mobilisation of glucose. This indicates that upon fasting FFA gain
      importance in hepatic metabolism. The hepatic sensitivity to adrenergic
      stimulation is enhanced upon fasting, as indicated by an increased beta2-value
      from 8.3 to 8.9.

PMID- 16102758
TI  - Characteristics of a thyroid hormone responsive reporter gene transduced into a
      Xenopus laevis cell line using lentivirus vector.
AB  - We introduced a self-inactivation (SIN) lentivirus vector (LV) into Xenopus
      laevis cell lines and established a permanent cell line expressing a reporter
      gene in a 3,5,3'-l-triiodothyronine (T(3)) dependent manner. The SIN LV contained
      the luciferase gene downstream from the X. laevis T(3)-response elements (TREs)
      and the SV40 promoter, and the enhanced green fluorescent protein (EGFP) gene
      downstream from the cytomegalovirus (CMV) promoter. It was integrated into the
      genome of X. laevis XL58, XTC2, and KR cells. The SIN LV transduced the X. laevis
      cells as efficiently as mammalian cells; however, the expression of EGFP in the
      transgene decreased with increasing culture time. A cell clone exhibiting the
      highest TH-dependent luciferase gene expression (XL58-TRE-Luc clone) was isolated
      from the EGFP-positive XL58 cell pool and characterized. The minimum effective
      concentration of T(3) that significantly induced the luciferase gene expression
      was 10(-11)M in the XL58-TRE-Luc clone. The application of the luciferase gene
      assay using the permanent XL58-TRE-Luc clone for the screening of thyroid
      disrupting chemicals revealed that tetrachlorobisphenol A, at 10(-6)M, had a weak
      T(3)-agonist activity, whereas trichlorobisphenol A, at 10(-8) - 10(-6)M had a
      weak T(3)-antagonist activity. Our results indicated that the permanent X. laevis
      cell line containing a T(3)-response transgene could be used as a bioassay, with
      small intra-assay variation, for the rapid screening, identification, and
      characterization of the thyroid-disrupting chemicals.

PMID- 16102759
TI  - Dimerizations of the wallaby gonadotropin-releasing hormone receptor and its
      splice variants.
AB  - Dimerization between wallaby GnRH-R and its splice variants was examined. A
      baculovirus-based fluorescence resonance energy transfer (Bv-FRET) assay was used
      to assess protein-protein interaction between wild type wallaby GnRH-R and splice
      variants (GnRH-RDelta1 and GnRH-RDelta2). FRET analysis demonstrated that GnRH-R,
      GnRH-RDelta1 or GnRH-RDelta2 are capable of assembling as homodimers. When GnRH-R
      is co-expressed with GnRH-RDelta1 or GnRH-RDelta2 splice variants, GnRH-R can
      form heterodimers with GnRH-RDelta1 and GnRH-RDelta2. GnRH agonist is not
      required for the initiation of dimerization. However, the addition of a GnRH
      agonist enhances the FRET signal in the GnRH-R homodimers, indicating that the
      GnRH agonist may be involved in modulating the extent of dimerization. In
      addition, this study reveals that dimerization of GnRH-R may be mediated by two
      or more protein interaction domains. One of them is probably located between
      amino acid residues 74 and 174, and the other one between residues 175 and 328.
      This is the first study to show dimerization between a wild type mammalian GnRH-R
      and its splice variants. It provides additional support for the potential
      involvement of splice variants in GnRH-R signaling.

PMID- 16102760
TI  - Transfer pathways between the ovaries and the uterus in the cebus monkeys (Cebus
      apella).
AB  - The aim of this work was to study, in the Cebus apella monkey, the developmental
      changes in the microanatomy of the utero-ovarian ligament (UOL) and whether their
      vascular and neural elements might be involved in the transfer of signals between
      the ovaries and uterus. Sections including uterus, UOL, and ovary obtained from
      two foetuses, two prepubertal, and four cycling monkeys, two of them treated with
      a neuron-axonal tracer, diamidino yellow (DY) into the corpus luteum (CL) and the
      remaining two into the endometrium, were analyzed for the expression of
      neurofilament protein (NFP) and tracer distribution. Eight regularly cycling
      females were used to investigate the transfer to the CL of pulses of
      prostaglandin F(2alpha) (PGF(2alpha)) (n=4) or its vehicle (n=4) given intra
      uterus. A convoluted artery, in conjunction with various vein channels, passed
      over the UOL allowing for a direct communication between uterus and ovaries. The
      artery acquired prominence during adulthood, in a manner well suited with the
      ovarian status. Immunohistochemical analysis revealed that NFP expression by the
      oocyte and by the endometrial epithelial cells was a highly conserved feature
      during development, whereas the appearance of NFP fibers in the ovaries, UOL, and
      uterus was a late event in the ontogenesis, likely regulated by the hormonal
      environment. Neurons, as an obvious source for these NFP fibers, were not
      recognized at any developmental stage, although some neuron-like cells were
      observed within the CL. The pattern displayed by the tracer DY, further suggested
      a reciprocal axonal transport among endometrial cells and follicular and luteal
      cells of both ovaries and between the ovaries themselves. The functionality of
      the utero-ovarian connection was assessed after injecting PGF(2alpha) intra
      uterus. A short exposition to PGF(2alpha) pulses was required for lowering
      ovarian and peripheral progesterone concentrations causing luteolysis, indicating
      that transport mechanism operating between uterus and ovary must be very
      efficient. The results suggest that the vessels and axons contained in the UOL of
      the Capuchin monkeys might be two combined key pathways underlying the reciprocal
      transfer of signals controlling utero-ovarian homeostasis.

PMID- 16102761
TI  - Involvement of calcium and calmodulin in the regulation of ovarian
      steroidogenesis in Atlantic croaker (Micropogonias undulatus) and modulation by
      Aroclor 1254.
AB  - The involvement of calcium-dependent signal transduction pathways in the
      regulation of ovarian steroidogenesis was investigated in Atlantic croaker.
      Treatment with the calcium ionophores A23187 and ionomycin caused a 2- to 5-fold
      increase in basal steroid accumulation by croaker ovarian tissue in vitro. A23187
      potentiated human chorionic gonadotropin (hCG)-induced testosterone (T)
      accumulation, whereas it inhibited accumulation of estradiol-17beta (E(2)) and
      the conversion of T to E(2), suggesting that intracellular calcium modulates
      aromatase enzyme activity. Gonadotropin stimulation of ovarian steroidogenesis
      was decreased in the presence of EGTA and inhibitors of voltage-sensitive calcium
      channels (VSCCs) and inositol-1,4,5-triphosphate-receptors (IP(3)Rs), indicating
      that releases of calcium from both intracellular and extracellular stores are
      components of the signal transduction pathways initiated by gonadotropin.
      Calmodulin is also involved in the regulation of ovarian steroidogenesis in
      croaker, since the calmodulin inhibitors W-7 and trifluoperazine (TFP) attenuated
      hCG-stimulated T and E(2) accumulation. These results are broadly similar to
      those reported previously in goldfish and suggest that the major calcium
      dependent signaling pathways involved in gonadotropin stimulation of ovarian
      steroidogenesis in tetrapods are also present in teleosts. In addition, the
      involvement of calcium in the regulation of aromatase activity was demonstrated
      for the first time in a vertebrate ovary. Finally, acute exposure to 0.001-1 ppm
      Aroclor 1254 induced up to a 5-fold increase in hCG-stimulated E(2) accumulation,
      and this effect was attenuated by co-treatment with inhibitors of VSCCs and
      calmodulin, suggesting the existence of a novel mechanism of endocrine disruption
      by an environmental contaminant involving alteration of calcium-dependent
      signaling pathways regulating steroidogenesis.

PMID- 16102762
TI  - Relationship between plasma growth hormone concentrations and temperament in
      mithuns (Bos frontalis).
AB  - The aim of the present study was to verify whether or not plasma growth hormone
      (GH) concentrations are correlated with temperament in mithuns (Bos frontalis), a
      semiwild ruminant. Therefore, a total of 69 female mithuns from four different
      strains, viz., Arunachal, Nagaland, Mizoram, and Manipur, were divided into six
      age groups (Group I, 0-6 months; Group II, >6-12 months; Group III, >1-2 years;
      Group IV, >2-2.5 years; Group V, >2.5-3.0 years; Group VI, >3.0 years). Blood
      samples were collected weekly for 6 consecutive weeks and assayed for plasma GH.
      Temperament was scored on a 6-point scale, 6 were being very aggressive and 1
      docile. Body weights of all animals were recorded once a week for 6 consecutive
      weeks GH concentrations and temperament scores were found to differ significantly
      between groups. Strain had significant effects on blood GH levels and
      temperament. Blood GH concentrations and temperament of Manipur mithuns were
      significantly higher than those of the other three strains within each group, for
      all groups. Across groups III to VI, blood GH levels and temperament among
      Nagaland, Mizoram, and Arunachal mithuns did not differ. Overall, the strain with
      the highest blood GH concentrations also had highest temperament scores. The
      Manipur strain had the highest blood GH levels and exhibited the most aggression
      (r = 0.95), and Arunachal mithuns, the lowest (r = 0.93). Temperament scores
      tended to decrease with increasing age for all four strains. Coefficients of
      correlation between blood GH and temperament among strains within each group, for
      all groups, were found to be significant. The highly positive correlation (r =
      0.94) between blood GH concentrations and temperament for all animals, regardless
      of age and strain differences, clearly indicates the relationship between blood
      GH and temperament in mithuns. In conclusion, our results suggest that peripheral
      blood GH levels can influence temperament in mithuns.

PMID- 16102763
TI  - Mobbing vocalizations as a coping response in the common marmoset.
AB  - Using a non-invasive method of sampling saliva followed by assay for cortisol
      levels, we found that common marmosets (Callithrix jacchus) show a decrease in
      cortisol levels after seeing a snake-model stimulus that reliably elicits mobbing
      (tsik) calls. In fact, there was a significant positive correlation between the
      number of tsik vocalizations made and the magnitude of the decrease in the
      cortisol concentrations. Furthermore, marmosets with higher levels of cortisol
      prior to being exposed to the stimulus produce more tsik calls than those with
      lower levels of cortisol. Subsequent experiments showed that, in response to 15
      min of isolation with no visual or auditory contact with conspecifics (a
      traditional stressor), cortisol levels increased significantly. However, playback
      of the mobbing calls of a familiar conspecific to individual isolated marmosets
      not only prevented the rise in cortisol, but also actually caused a decrease in
      the levels of this hormone. This suggests that the mobbing calls serve to calm
      the marmoset after experiencing a stressful situation. This finding results in a
      greater understanding as to the role of physiological responses during
      communication in this species and could have implications for the welfare of
      marmosets in captivity.

PMID- 16102764
TI  - Current concepts of molecular aspects of bone healing.
AB  - Fracture healing is a complex physiological process. It involves the coordinated
      participation of haematopoietic and immune cells within the bone marrow in
      conjunction with vascular and skeletal cell precursors, including mesenchymal
      stem cells (MSCs) that are recruited from the surrounding tissues and the
      circulation. Multiple factors regulate this cascade of molecular events by
      affecting different sites in the osteoblast and chondroblast lineage through
      various processes such as migration, proliferation, chemotaxis, differentiation,
      inhibition, and extracellular protein synthesis. An understanding of the fracture
      healing cellular and molecular pathways is not only critical for the future
      advancement of fracture treatment, but it may also be informative to our further
      understanding of the mechanisms of skeletal growth and repair as well as the
      mechanisms of aging.

PMID- 16102765
TI  - Follicle stimulating hormone as a predictor of ovarian response in women
      undergoing controlled ovarian hyperstimulation for IVF.
AB  - OBJECTIVE: To evaluate the effect of basal follicle stimulating hormone (FHS)
      level on ovarian response in women undergoing controlled ovarian hyperstimulation
      for in vitro fertilization. METHODS: A descriptive and analytic study of 212
      cycles of IVF chosen from about 2200 files of women treated at Royan Institute,
      Tehran, Iran, from 1991 to 1999. Treatment was started with intranasal or
      subcutaneous buserlin (0.5 cm3), on day 21 (long protocol). On day 2 of the next
      cycle, stimulation with human menopausal gonadotropin (hMG) was initiated. When
      the number and size of follicles were suitable, human chorionic gonadotropin
      (hCG) was given intramuscularly for ovulation induction, followed by oocyte
      retrieval 36 to 40 h later. Embryos were transferred about 48 to 72 h after
      oocyte retrieval. The women were assigned to 2 groups on the basis of day 3 serum
      FSH levels (>or=15 IU/mL, group 1 and <15 IU/mL, group 2). RESULTS: There were
      statistically significant differences between the 2 groups in number of
      follicles, number of oocytes retrieved and embryos transferred (lower in group
      1), and level of serum luteinizing hormone and number of canceled cycles (higher
      in group 1). There were no statistical differences in number of ampoules of hMG
      used or age of patients. CONCLUSION: Day-3 serum FSH level was a predictor of
      ovarian response and IVF outcome in this study.

PMID- 16102766
TI  - Vaginal misoprostol for cervical priming before hysteroscopy in perimenopausal
      and postmenopausal women.
AB  - OBJECTIVE: To evaluate the effectiveness and possible adverse effects of vaginal
      misoprostol for cervical priming before hysteroscopy in perimenopausal and
      postmenopausal women. METHODS: A total of 105 women scheduled for hysteroscopy
      were randomly assigned to 2 groups. The study group (n=51) received 400 microg of
      vaginal misoprostol at least 12 h before the procedure and the control group
      (n=54) received no cervical priming agent. The primary outcome measure was the
      number of women who required cervical dilation. Secondary outcomes were cervical
      width (the largest size of Hegar dilator inserted without resistance) as well as
      complications and adverse effects. RESULTS: In the misoprostol group 27 women
      (52.9%) required cervical dilation vs. 53 (98.1%) in the control group
      (P<0.0001). The largest size of Hegar dilator inserted without resistance was
      7.6+/-1.4 mm in the misoprostol group vs. 5.0+/-1.1 mm in the control group
      (P<0.0001). A similar effect of misoprostol on cervical dilation was also found
      in the subgroup of treated postmenopausal women. Only 2 women (3.9%) experienced
      mild lower abdominal pain after misoprostol application. CONCLUSION: Vaginal
      misoprostol applied before hysteroscopy reduced cervical resistance and the need
      for cervical dilation in perimenopausal and postmenopausal women, with only mild
      adverse effects.

PMID- 16102767
TI  - What is important to measure in the last months and weeks of life?: A modified
      nominal group study.
AB  - BACKGROUND: Identifying the most important issues for palliative care patients
      and their families, and assessing whether services address these appropriately is
      important. Little is known about the views of United Kingdom service users and
      whether, and in what ways, they differ from those in the published literature
      from other countries, or from health professionals. AIMS: To investigate what is
      important to measure at the end of life from the perspectives of United Kingdom
      patients, bereaved relatives and health care professionals. METHODS: Ten focus
      groups, using a modified nominal group technique, with a total of 75 participants
      (10 patients, 35 professionals and 30 bereaved relatives) enabled issues
      participants thought important to measure at the end of life to be identified and
      prioritised using ratings and rankings. Thematic analysis of the data was
      conducted to enable cross-group comparison. FINDINGS: Seven themes were
      identified as most important to participants: symptom management; choice and
      control; dignity; quality of life; preparation; relationships; and co-ordination
      and continuity. Bereaved relatives and professionals emphasised symptom
      management, relationships and quality of life, whilst patients prioritised issues
      around preparation. CONCLUSIONS: The study was successful in identifying aspects
      of end of life care that are important to patients, families and health
      professionals in the United Kingdom. Although participants were not
      representative of the wider population in the United Kingdom, the degree of
      concordance with published studies from outside the United Kingdom increases the
      credibility of the findings. Quality assurance initiatives need to ensure that
      they act on information such as this on users' priorities. Further research is
      needed to test out the findings in other settings in the United Kingdom, to build
      on the findings about different participants' views and to identify similarities
      and variations between countries.

PMID- 16102768
TI  - Emotional comfort: the patient's perspective of a therapeutic context.
AB  - BACKGROUND: Comfort is a word that is frequently used to describe both physical
      and emotional aspects of the hospital experience. A number of definitions exist
      in the literature and there is a lack of clarity in understanding this concept.
      OBJECTIVES: This paper describes the therapeutic context of emotional comfort
      that was identified in a qualitative study that sought to explain the perceived
      therapeutic effect of interpersonal interactions that were experienced by
      patients during hospitalisation. DESIGN: Grounded theory. SETTINGS: Public and
      private hospitals situated in Perth, Western Australia. PARTICIPANTS: 40 patient
      participants from a variety of settings, and 32 nurse participants. All
      participants were over the age of 18 and spoke English. METHODS: Formal and
      informal interviews, field observations. RESULTS: Patients interpreted the
      interpersonal interactions that they experienced during hospitalisation in terms
      of their experience of emotional comfort or discomfort. A central feature of
      emotional comfort was the patient's perception of personal control. CONCLUSIONS:
      This study provides a greater understanding of the concept of comfort from the
      perspective of hospitalised patients. It highlights that patients approach their
      illnesses or injuries perceiving that a connection exists between the mind and
      the body.

PMID- 16102769
TI  - Human behaviour and the epidemiology of parasitic zoonoses.
AB  - The behaviour of Homo sapiens has a pivotal role to play in the macro and
      microepidemiology of emerging or re-emerging parasitic zoonoses. Changing
      demographics and the concomitant alterations to the environment, climate,
      technology, land use and changes in human behavior, converge to favour the
      emergence and spread of parasitic zoonoses. The recent unprecedented movements of
      people, their animals and their parasites around the world, introduce and mix
      genes, cultural preferences, customs, and behavioral patterns. The increasing
      proclivity for eating meat, fish, crabs, shrimp, molluscs raw, undercooked,
      smoked, pickled or dried facilitates a number of protozoan (Toxoplasma),
      trematode (Fasciola sp., Paragonimus spp., Clonorchis sp., Opisthorchis spp.,
      Heterophyes sp., Metagonimus sp., Echinostoma spp., Nanophyetus sp.) cestode
      (Taenia spp, Diphyllobothrum sp.) and nematode (Trichinella spp., Capillaria
      spp., Gnathostoma spp., Anisakis sp., Parastrongylus spp.) caused zoonoses. The
      increasing world population and the inability to keep pace with the provision of
      adequate sanitation and clean, safe drinking water, has led to an increased
      importance of waterborne zoonoses, such as those caused by Giardia,
      Cryptosporidium and Toxoplasma. Our close relationship with and the numerous uses
      to which we put companion animals and their ubiquitous distribution has resulted
      in dogs and cats unwitting participation in sharing over 60 parasite species
      including: Giardia, Cryptosporidium, Toxoplasma, most foodborne trematode
      species, Diphyllobothrum, Echinococcus spp., Ancylostoma and Toxocara. Changing
      human behaviour through education, to encourage the proper cooking of food, which
      may have cultural and social significance, will remain as challenging as
      controlling stray and feral pet populations, improving hygiene levels and the
      provision of safe drinking water and the proper use of sanctuary facilities. Long
      pre-patent periods and the normally insidious sub-clinical nature of most
      zoonoses makes advice requiring behavioural change for their control a difficult
      task. Our clearer understanding of the heterogeneity of susceptibility to
      infection, the complex genetic variations of people and parasite species and the
      development of molecular epidemiological tools is shedding more light on
      transmission routes and the spectrum of disease that is observed. Improved and
      new serological, molecular and imaging diagnostic tests and the development of
      broad spectrum chemotherapeutic agents has led to the attenuation of morbidity
      and mortality due to parasitic zoonoses in economically advantaged regions. Such
      advancements, in partnership with supportive behavioural change, has the
      potential for a sustainable global reduction in the burden of ill health due to
      parasitic zoonoses. Whether this will materialise is a challenge for us all.

PMID- 16102770
TI  - Proteome of Aedes aegypti larvae in response to infection by the intracellular
      parasite Vavraia culicis.
AB  - We report on the modification of the Aedes aegypti larval proteome following
      infection by the microsporidian parasite Vavraia culicis. Mosquito larvae were
      sampled at 5 and 15 days of age to compare the effects of infection when the
      parasite was in two different developmental stages. Modifications of the host
      proteome due to the stress of infection were distinguished from those of a more
      general nature by treatments involving hypoxia. We found that the major reaction
      to stress was the suppression of particular protein spots. Older (15 days) larvae
      reacted more strongly to infection by V. culicis (46% of the total number of
      spots affected; 17% for 5 days larvae), while the strongest reaction of younger
      (5 days) larvae was to hypoxia for pH range 5-8 and to combined effects of
      infection and hypoxia for pH range 3-6. MALDI-TOF results indicate that proteins
      induced or suppressed by infection are involved directly or indirectly in defense
      against microorganisms. Finally, our MALDI-TOF results suggest that A. aegypti
      larvae try to control or clear V. culicis infection and also that V. culicis
      probably impairs the immune defense of this host via arginases-NOS competition.

PMID- 16102771
TI  - Changes in antigenic profile during culture of Neoparamoeba sp., causative agent
      of amoebic gill disease in Atlantic salmon.
AB  - Amoebic gill disease (AGD), the most serious infectious disease affecting farmed
      salmon in Tasmania, is caused by free-living marine amoeba Neoparamoeba sp. The
      parasites on the gills induce proliferation of epithelial cells initiating a
      hyperplastic response and reducing the surface area available for gaseous
      exchange. AGD can be induced in salmon by exposure to freshly isolated
      Neoparamoeba from AGD infected fish, however cultured Neoparamoeba are non
      infective. We describe here antigenic differences between freshly isolated and in
      vitro cultured parasites, and within individual isolates of the parasite cultured
      under different conditions. Immunoblot analysis using polyclonal antisera,
      revealed differences in the antigen profiles of two cultured isolates of
      Neoparamoeba sp. when they were grown on agar versus in liquid medium. However,
      the antigen profiles of the two isolates were very similar when they were grown
      under the same culture conditions. Comparison of these antigen profiles with a
      preparation from parasites freshly isolated from infected gills revealed a very
      limited number of shared antigens. In addition monoclonal antibodies (mAbs)
      raised against surface antigens of cultured parasites were used in an indirect
      immunofluorescence assay to assess the expression of specific surface antigens of
      Neoparamoeba sp. after various periods in culture. Significant changes in antigen
      expression of freshly isolated parasites were observed after 15 days of in vitro
      culture. The use of mAb demonstrated progressive exposure/expression of
      individual antigens on the surface of the freshly isolated parasites during the
      period in culture.

PMID- 16102772
TI  - Plasma insulin levels predict atherosclerotic lesion burden in obese
      hyperlipidemic mice.
AB  - Despite a clear association between obesity, insulin resistance and
      atherosclerosis in humans, to date, no animal models have been described in which
      insulin resistance is associated with atherosclerotic lesion burden. Using two
      mouse models of obesity-induced hyperlipidemia:leptin deficient (ob/ob) mice on
      an apolipoprotein E deficient (apoE-/-) or low density lipoprotein receptor
      deficient (LDLR-/-) background, we sought to determine metabolic parameters most
      closely associated with atherosclerotic lesion burden. Total plasma cholesterol
      (TC) levels in ob/ob;apoE-/- mice and ob/ob;LDLR-/- mice were indistinguishable
      (682+/-48 versus 663+/-16, respectively). Analysis of lipoprotein profiles showed
      that cholesterol was carried primarily on VLDL in the ob/ob;apoE-/- mice and on
      LDL in the ob/ob;LDLR-/- mice. Plasma triglycerides (TG) were 55% lower
      (P<0.001), non-esterified fatty acids (NEFA) were 1.5-fold higher (P<0.01), and
      insulin levels were 1.7-fold higher (NS) in ob/ob;apoE-/- mice compared to
      ob/ob;LDLR-/- mice. Other parameters such as body weight, fat pad weight, and
      glucose levels were not different between the groups. Aortic sinus lesion area of
      ob/ob;apoE-/- mice was increased 3.2-fold above ob/ob;LDLR-/- mice (102,455+/
      8565 microm2/section versus 31,750+/-4478 microm2/section, P<0.001). Lesions in
      ob/ob;apoE-/- mice were also more complex as evidenced by a 7.7-fold increase in
      collagen content (P<0.001). Atherosclerotic lesion area was positively correlated
      with body weight (P<0.005), NEFA (P=0.007), and insulin (P=0.002) levels in the
      ob/ob;LDLR-/- mice and with insulin (P=0.014) in the ob/ob;apoE-/- mice. In
      contrast, lesion burden was neither associated with TC and TG, nor with
      individual lipoprotein pools, in either animal model. These data provide a direct
      demonstration of the pathophysiologic relevance of hyperinsulinemia, NEFA, and
      increased body weight to atherosclerotic lesion formation.

PMID- 16102773
TI  - Cardiac isoform of alpha-2 macroglobulin--a new biomarker for myocardial
      infarcted diabetic patients.
AB  - Cardiac isoform of alpha-2 macroglobulin [cardiac alpha2M] has been shown to be
      an early marker in cardiac hypertrophy and left ventricular mass in humans. We,
      here, for the first time report its presence in myocardial infarcted humans and
      tried to explore the possibility of using this protein as a novel diagnostic
      marker for myocardial infarcted diabetic patients. A total of 260 samples were
      analyzed in this study for the presence of cardiac alpha2M. These include 55
      patients of diabetic with post myocardial infarction [PMI], 45 diabetic patients
      without PMI, 60 patients of PMI alone and 100 controls without any ailments.
      Levels of cardiac alpha2M present in the sera of diabetic patients with PMI are
      significantly higher than that of normal human sera and diabetic patients without
      PMI but not with PMI alone group, suggesting this protein as a marker for PMI
      itself. However, our results reveal that cardiac alpha2M could be a valuable
      marker for the diagnosis of myocardial infarcted diabetic patients and
      differentiating them from diabetic patients without myocardial infarction by
      sandwich ELISA.

PMID- 16102774
TI  - Endothelium-dependent vasodilation and carotid artery wall remodeling in athletes
      and sedentary subjects.
AB  - In this study, the relationship between age, carotid artery remodeling, and
      endothelium-dependent vasodilation is investigated in sedentary subjects and
      athletes. Thirty-two young and old healthy sedentary subjects and 32 age-matched
      endurance athletes underwent ultrasonography of the carotid wall for measuring
      intima-media thickness (IMT) and corrected integrated backscatter (C-IBS), two
      early indicators of the atherosclerosis process. Endothelium-dependent
      vasodilation was assessed by intra-brachial acetylcholine (strain-gauge
      plethysmography), at baseline and during NO sythase inhibitor NG-monomethyl-L
      arginine (L-NMMA), and the antioxidant Vitamin C. Response to sodium
      nitroprusside (SNP) was also evaluated. Independently of trained status, IMT and
      C-IBS were higher in older than in young individuals (p<0.0001), while response
      to acetylcholine, but not to SNP, was lower (p<0.0001). Older athletes showed
      lower IMT, lower C-IBS (p<0.0001), greater response to acetylcholine (p<0.0001),
      and greater inhibition of acetylcholine by L-NMMA (p<0.001) than older controls.
      Only in older sedentary individuals, Vitamin C increased response to
      acetylcholine (p<0.001) and restored the inhibiting effect of L-NMMA (p<0.01). In
      the whole population maximal acetylcholine-induced vasodilation was inversely
      related to IMT (r=-0.60, p<0.0001) and to C-IBS (r=-0.56, p<0.0001). In
      conclusion, regular physical training can attenuate the age-related impairment of
      endothelium-dependent vasodilation, which is related to an attenuation of the age
      induced remodeling of the carotid wall.

PMID- 16102775
TI  - Comparative analysis of the structure of sterically stabilized ferrofluids on
      polar carriers by small-angle neutron scattering.
AB  - Results of experiments on small-angle neutron scattering from ferrofluids on
      polar carriers (pentanol, water, methyl-ethyl-ketone), with double-layer sterical
      stabilization of magnetic nanoparticles, are reported. Several types of spatial
      structural organization are observed. The structure of highly stable pentanol
      based samples is similar to that of stable ferrofluids based on organic non-polar
      carriers (e.g., benzene) with mono-layer covered magnetic nanoparticles. At the
      same time, the effect of the interparticle interaction on the scattering is
      stronger in polar ferrofluids because of the structural difference in the
      surfactant shell. The structure of the studied methyl-ethyl-ketone- and water
      based ferrofluids essentially different from the previous case. The formation of
      large (>100 nm in size) elongated or fractal aggregates, respectively, is
      detected even in the absence of external magnetic field, which corresponds to
      weaker stability of these types of ferrofluids. The structure of the fractal
      aggregates in water-based ferrofluids does not depend on the particle
      concentration, but it is sensitive to temperature. A temperature increase results
      in a decrease in their fractal dimension reflecting destruction of the
      aggregates. In addition, in water-based ferrofluids these aggregates consist of
      small (radius approximately 10 nm) and temperature-stable primary aggregates.

PMID- 16102776
TI  - Streaming potential across cation-exchange membranes in methanol-water
      electrolyte solutions.
AB  - Streaming potential measurements across charged membranes separating two equal
      solutions have been carried out. Two cation-exchange membranes with different
      cross-linked and swelling properties (Ionics and Nafion membranes) and methanol
      water electrolyte solutions of KCl have been used in the experiments. The
      obtained results show that the streaming potential is higher for the Ionics
      membrane and that the values depend on the methanol content of the solutions. A
      different behavior is found in the dependence of the streaming potential on the
      methanol percentage for each membrane. The study of the relaxation times in the
      decay of electrokinetic steady states of streaming potential has been carried out
      from the time dependence of the streaming potential when the pressure difference
      through the membrane is suppressed. The results show the existence of two
      different parts or partial relaxations, mechanical and electric. A different
      behavior of the mechanical relaxation time with the methanol percentage has been
      found for the two membranes, but any significant difference between their
      electric relaxation times. These differences have been explained in terms of the
      different degree of swelling of the membranes used.

PMID- 16102777
TI  - Molecular modeling study of the aggregation behavior of nickel(II), cobalt(II),
      lead(II) and zinc(II) bis(2-ethylhexyl) phosphate complexes.
AB  - The physiochemical nature of the metal-extractant species in organic solvent has
      been a matter of debate over liquid-liquid extraction of transition metals by
      bis(2-ethylhexyl) phosphate. The aggregation behavior of nickel(II), cobalt(II),
      lead(II), and zinc(II) bis(2-ethylhexyl) phosphate have been investigated using
      molecular modeling. The recently confirmed "open" water channels rodlike reversed
      micelles which is in contact with the nonaqueous solvent rather than in an inner
      core (or "closed" water channel) of the nickel-extractant species by Ibrahim and
      Neuman appears to be a unique structure for such species. Lead-, cobalt- and zinc
      extractant species behave in a different manner. The cobalt-extractant species
      form rodlike reversed micelles, but does not show the formation of any open water
      channel. The zinc- and lead-extractant species form ellipsoidal (or deformed
      spherical) reversed micelles with fewer water molecules located at the core of
      the micelles which is in accord with the conventional view of reversed micelles.
      The structural variations of the reversed micelles for the metal extracted
      species are in accord with the known extraction behavior of such metals when
      using HDEHP.

PMID- 16102778
TI  - Solid-liquid interfacial energy as a tool to estimate shifts in isoelectric
      points of adsorbed proteins on solid surfaces.
AB  - This work reports the estimation of isoelectric points (pIs) of adsorbed amino
      acids and proteins on solid surfaces in the pH range between 3.5-11.0 from a
      measurement of solid/liquid interfacial energy. The values thus obtained are
      compared with the pIs determined in solution phase by other methods. Both glass
      and Teflon have been chosen as model solid surfaces. Close agreement between the
      reference pI values, obtained by the capillary isoelectric focusing and those
      obtained at solid/liquid interface is observed within an average difference of
      0.04-0.08 pH unit when the pIs are above the pI of glass. For systems whose pIs
      are far away from that of glass (either in the acidic or highly alkaline range),
      a large shift in the isoelectric point is observed. In case of Teflon the pIs are
      closer to the reported values than at glass/liquid interface. This could be due
      to the fact that Teflon being a hydrophobic surface, its surface is dominated by
      dispersive forces, which may not be seriously affected by pH changes. The shift
      in the values at solid/liquid interface compared to that in solution have been
      examined using an 'image charge approach.'

PMID- 16102779
TI  - Heterogeneous Do-Do model of water adsorption on carbons.
AB  - The model of water adsorption on carbons proposed five years ago by Do and Do is
      analyzed and improved. Following the experimental evidence that for activated
      carbons surface active groups differ in the value of the energy of interaction
      with water molecules, we propose to extend the original model to take this
      fundamental feature into account. For the original DD model, as well as proposed
      new heterogeneous one (HDDM), we develop also the corresponding isosteric
      enthalpy of adsorption formulas. The features of the HDDM are studied via
      simulations. It is shown that the new model predicts the shapes of adsorption
      isotherm as well as corresponding enthalpy observed for real experimental
      systems. Finally, the HDDM is successfully applied to description of arbitrarily
      chosen adsorption and enthalpy of adsorption data. Up to our knowledge, HDDM is
      the first model describing satisfactorily water adsorption isotherms and
      corresponding enthalpy data measured on different microporous activated carbons
      in the whole relative pressure range.

PMID- 16102780
TI  - Three-month-olds' sensitivity to orientation cues in the three-dimensional depth
      plane.
AB  - Three-month-olds are sensitive to orientation changes of line drawings when they
      have a three-dimensional (3-D) interpretation and when the changes are defined by
      both 3-D depth and two-dimensional (2-D) picture plane cues [Bhatt, R. S., &
      Bertin, E. (2001). Pictorial cues and three-dimensional information processing in
      early infancy. Journal of Experimental Child Psychology, 80, 315-332]. In the
      current study, we examined whether 3-month-olds are sensitive to pictorial line
      junction cues that signal orientation changes solely in the 3-D depth plane. The
      results revealed that infants discriminated a misoriented elongated cube in an
      array when the stimuli contained both shading and lines (Experiment 2) but not
      when only lines depicted the elongated cubes (Experiment 1). Testing with
      comparable 2-D images revealed that, even in the presence of shading information,
      detection of orientation changes is specific to images that have a 3-D
      interpretation. Together, the results suggest that 3-month-olds are sensitive to
      pictorial line junction cues that signal orientation changes in the 3-D depth
      plane to adults provided that shading information is available and the images
      have a 3-D interpretation.

PMID- 16102781
TI  - Friendship, cliquishness, and the emergence of cooperation.
AB  - The evolution of cooperation is a central problem in biology and the social
      sciences. While theoretical work using the iterated prisoner's dilemma (IPD) has
      shown that cooperation among non-kin can be sustained among reciprocal strategies
      (i.e. tit-for-tat), these results are sensitive to errors in strategy execution,
      cyclical invasions by free riders, and the specific ecology of strategies.
      Moreover, the IPD assumes that a strategy's probability of playing the PD game
      with other individuals is independent of the decisions made by others. Here, we
      remove the assumption of independent pairing by studying a more plausible
      cooperative dilemma in which players can preferentially interact with a limited
      set of known partners and also deploy longer-term accounting strategies that can
      counteract the effects of random errors. We show that cooperative strategies
      readily emerge and persist in a range of noisy environments, with successful
      cooperative strategies (henceforth, cliquers) maintaining medium-term memories
      for partners and low thresholds for acceptable cooperation (i.e. forgiveness).
      The success of these strategies relies on their cliquishness-a propensity to
      defect with strangers if they already have an adequate number of partners.
      Notably, this combination of medium-term accounting, forgiveness, and
      cliquishness fits with empirical studies of friendship and other long-term
      relationships among humans.

PMID- 16102782
TI  - Hsp70 does not mediate the hyperthermia-associated hyporesponsiveness to
      angiotensin in isolated rat portal veins.
AB  - In rat portal veins (RPV) isolated from septic rats, we previously showed that
      the contractile response to angiotensin II (AT(II)) was significantly decreased
      and that the vascular failure was correlated with the severity of the disease. We
      hypothesized that hyperthermia might be one of the factors responsible for the
      vascular failure. Moreover, hyperthermia should concomitantly increase heat shock
      proteins (Hsps) expression. We then compared the vascular contractility and the
      heat shock protein 70 (Hsp70) expression in RPV incubated at 37 degrees C and
      39.5 degrees C and sought for a relationship between both events. In our
      experimental model, hyperthermia increased the Hsp70 expression and decreased the
      contractile response to AT(II). Incorporation of the Hsp70 antisense
      oligonucleotide in RPV blocked the increase in Hsp70 expression but had no
      consequence on the contractile response to AT(II). In conclusion, hyperthermia
      increases Hsp70 expression but does not mediate the decreased response to AT(II).
      Hsp70 overexpression has no effect on the actin-myosin interaction in vascular
      smooth muscle.

PMID- 16102783
TI  - Reversal of morphine, methadone and heroin induced effects in mice by naloxone
      methiodide.
AB  - Opioid overdose, which is commonly associated with opioid induced respiratory
      depression, is a problem with both therapeutic and illicit opioid use. While the
      central mechanisms involved in the effects of opioids are well described, it has
      also been suggested that a peripheral component may contribute to the effects
      observed. This study aimed to further characterise the effects of the
      peripherally acting naloxone methiodide on the respiratory, analgesic and
      withdrawal effects produced by various opioid agonists. A comparison of the
      respiratory and analgesic effects of morphine, methadone and heroin in male Swiss
      Albino mice was conducted and respiratory depressive ED(80) doses of each opioid
      determined. These doses (morphine 9 mg/kg i.p., methadone 7 mg/kg i.p., and
      heroin 17 mg/kg i.p.) were then used to show that both naloxone (3 mg/kg i.p.)
      and naloxone methiodide (30-100 mg/kg i.p.) could reverse the respiratory and
      analgesic effects of these opioid agonists, but only naloxone precipitated
      withdrawal. Further investigation in female C57BL/6J mice using barometric
      plethysmography found that both opioid antagonists could reverse methadone
      induced decreases in respiratory rate and increases in tidal volume. Its effects
      do not appear to be strain or sex dependent. It was concluded that naloxone
      methiodide can reverse the respiratory and analgesic actions of a variety of
      opioid agonists, without inducing opioid withdrawal.

PMID- 16102784
TI  - Breaking the relay in deregulated cellular signal transduction as a rationale for
      chemoprevention with anti-inflammatory phytochemicals.
AB  - Center to the cancer biology is disrupted intracellular signaling network, which
      transmits improper signals resulting in abnormal cellular functioning. Therefore,
      modulation of inappropriate cell signaling cascades might be a rational approach
      in achieving chemoprevention. Inflammation has long been suspected to contribute
      to carcinogenesis. A new horizon in chemoprevention research is the recent
      discovery of molecular links between inflammation and cancer. Components of the
      cell signaling network, especially those converge on redox-sensitive
      transcription factor nuclear factor-kappaB involved in mediating inflammatory
      response, have been implicated in carcinogenesis. Intracellular signaling through
      another redox-sensitive transcription factor AP-1 and that transmitted via a more
      recently identified oncoprotein beta-catenin are also considered to be crucial
      for inflammation-associated cancer. Epidemiological and experimental studies have
      revealed that a wide variety of phytochemicals present in our daily diet are
      potential chemopreventive agents that can alter or correct undesired cellular
      functions caused by abnormal pro-inflammatory signal transmission. Modulation of
      cellular signaling involved in chronic inflammatory response by anti-inflammatory
      phytochemicals may comprise a rational and pragmatic strategy in molecular target
      based chemoprevention.

PMID- 16102785
TI  - Design issues in cross-sectional biomarkers studies: urinary biomarkers of PAH
      exposure and oxidative stress.
AB  - Cross-sectional biomarker studies can provide a snapshot of the frequency and
      characteristics of exposure/disease in a population at a particular point in time
      and, as a result, valuable insights for delineating the multi-step association
      between exposure and disease occurrence. Three major issues should be considered
      when designing biomarker studies: selection of appropriate biomarkers, the assay
      (laboratory validity), and the population validity of the selected biomarkers.
      Factors related to biomarker selection include biological relevance, specificity,
      sensitivity, biological half-life, stability, and so on. The assay attributes
      include limit of detection, reproducibility/reliability, inter-laboratory
      variation, specificity, time, and cost. Factors related to the population
      validity include the frequency or prevalence of markers, greater inter-individual
      variation than intra-individual variation, intra-class correlation coefficients
      (ICC), association with potential confounders, invasiveness of specimen
      collection, and subject selection. Three studies are selected to demonstrate
      different features of cross-sectional biomarker studies: (1) characterizing the
      determinants of the biomarkers (study I: urinary PAH metabolites and
      environmental particulate exposure), (2) relationship of multiple biomarkers of
      exposure and effect (study II: relationship between urinary PAH metabolites and
      oxidative stress), and (3) evaluating gene-environmental interaction (study III:
      effect of genetic polymorphisms of GSTM1 on the association of green tea
      consumption and urinary 1-OHPG levels in shipbuilding workers).

PMID- 16102786
TI  - Role of NMDA receptors in the syndrome of behavioral changes produced by predator
      stress.
AB  - Effects on behavioral response to predator stress of competitive block of NMDA
      receptors with doses of .1, 1.0 and 10 mg/kg of CPP (3-(2-carboxypiperazin4
      yl)propyl-l-phosphonic acid) were studied. An affect test battery assessed
      behavioral response to stress and employed hole board, elevated plus maze,
      light/dark box, social interaction, social avoidance and response to acoustic
      startle tests. Doses of 1-10 mg/kg of CPP administered ip 30 min prior to
      predator stress blocked the effects of predator stress on some but not all
      behaviors measured 8-9 days later. Predator stress normally reduces open arm
      exploration and risk assessment in the plus maze, decreases entries into the
      lighted arm of the light dark box and delays habituation of the acoustic startle
      response. CPP blocked all of these effects of predator stress. A dose of 10 mg/kg
      of CPP was required for all behaviors except habituation to startle. Block of
      effects on habituation to startle occurred at 1 and 10 mg/kg. Behaviors in which
      effects of predator stress were not blocked by CPP included reduction in
      unprotected head dips in the elevated plus maze and reduced social interaction.
      In addition, predator stress was without effect on social avoidance measured with
      the Haller test. These findings extend previous work showing NMDA receptor
      dependence of effects of predator stress on behavior in the elevated plus maze
      and on amplitude of acoustic startle response. Novel findings include NMDA
      receptor dependence of predator stress effects on light dark box behavior and
      startle habituation. Taken together, the findings add to a body of evidence
      showing that a syndrome of behavioral changes follows predator stress. Components
      of this syndrome of behavioral changes likely depend on changes in separable
      neural substrates initiated in part by NMDA receptors as well as by other
      neurochemical means.

PMID- 16102787
TI  - Role of NMDA receptors in the lateralized potentiation of amygdala afferent and
      efferent neural transmission produced by predator stress.
AB  - The present study investigated the role of NMDA receptors in behavioral and
      neuroplastic changes in amygdala efferent (central amygdala to periaqueductal
      gray-ACE-PAG) and amygdala afferent (ventral angular bundle to basolateral
      amygdala-VAB-BLA) pathways in response to predator stress. Effects on brain and
      behavioral response to predator stress of competitive block of NMDA receptors
      with a dose of 10 mg/kg of CPP (3-(2-carboxypiperazin4-yl)propyl-l-phosphonic
      acid) were studied. Behavioral response to stress was tested with hole board,
      elevated plus maze, light/dark box, social interaction and acoustic startle
      tests. CPP was administered i.p. 30 min prior to predator stress and blocked the
      effects of predator on some but not all behaviors measured 8-9 days later.
      Effects of predator stress and CPP on potentials evoked in the PAG by single
      pulse stimulation of the ACE and in the BLA by single pulse stimulation of VAB
      were assessed 10-11 days after predator stress. Predator stress potentiated ACE
      PAG evoked potentials in the right but not the left hemisphere, replicating
      previous work. Predator stress potentiated VAB-BLA transmission in both
      hemispheres 10-11 days after predator stress. Right hemisphere VAB-BLA
      potentiation replicated and extended past studies showing right hemisphere
      potentiation at 1 and 9 days after stress. Left VAB-BLA potentiation effects
      differed from the long term depression seen in VAB-BLA at 1 and 9 days after
      stress in previous studies. CPP blocked predator stress-induced potentiation of
      ACE-PAG and VAB-BLA evoked potentials in the right hemisphere. CPP did not block
      left VAB-BLA potentiation, rather CPP amplified it. Left hemisphere effects of
      CPP were interpreted as reflecting block of NMDA dependent long term depression,
      which unmasked a non-NMDA dependent potentiation. Taken together, the findings
      add to a body of evidence suggesting that a syndrome of behavioral changes
      follows predator stress. Components of this syndrome likely depend on changes in
      separable neural substrates. Potentiation of ACE-PAG and VAB-BLA evoked
      potentials in the right hemisphere likely mediates a subset of changes in
      behavior. Moreover, a medial ACE-PAG pathway is implicated in mediating stress
      induced changes in startle amplitude. In contrast, a lateral ACE-PAG pathway is
      implicated in mediating changes in startle habituation. Finally, consistent with
      cat and human studies, the right hemisphere appears particularly important in
      long term response to stress.

PMID- 16102788
TI  - Brain imaging of serotonin after recovery from anorexia and bulimia nervosa.
AB  - Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders with
      relatively homogenous presentations such as age of onset and gender distribution.
      In addition, they share symptoms, such as extremes of food consumption, body
      image distortion, anxiety and obsessions, and ego-syntonic neglect. Taken
      together, these observations raise the possibility that these symptoms reflect
      disturbed brain function, which contributes to the pathophysiology of these
      illnesses. Several lines of evidence suggest that disturbances of serotonin (5
      HT) pathways play a role. First, 5-HT pathways contribute to the modulation of
      feeding, mood, and impulse control. Second, medications that act on 5-HT pathways
      have some degree of efficacy in individuals with AN and BN. Third, such
      disturbances are present when subjects are ill and persist after recovery,
      suggesting that 5-HT alterations may be traits that are independent of the state
      of the illness. Positron emission tomography (PET) with radioligands offers an
      opportunity to directly characterize brain 5-HT pathways and their relationship
      with behavior. For example, reduced 5-HT(2A) receptor function occurs in AN
      whereas increased 5-HT(1A) receptor function occurs in BN. Moreover, imaging
      studies correlate altered 5-HT(1A) and 5-HT(2A) receptor function with traits
      often found in individuals with AN and BN, such as harm avoidance. Finally,
      alteration of these receptors tends to implicate pathways involving frontal,
      cingulate, temporal, and parietal regions. Alterations of these circuits may
      affect mood and impulse control as well as the motivating and hedonic aspects of
      feeding behavior. Such imaging studies may offer insights into new pharmacology
      and psychotherapy approaches.

PMID- 16102789
TI  - Bioactive phenolic compounds from a medicinal lichen, Usnea longissima.
AB  - Natural products, longissiminone A (1) and longissiminone B (2), were isolated
      along with a known compound, glutinol (3), from a medicinal lichen, Usnea
      longissima. The structures of compounds 1 and 2 were determined with the help of
      spectroscopic studies. Compound 1 was found to possess potent anti-inflammatory
      activity in a cell-based contemporary assay. Cytotoxicity activity measured by
      cell viability assay showed 100% viability in the presence of 200 microg/mL conc.
      of these compounds.

PMID- 16102790
TI  - Primary hepatic actinomycosis.
AB  - Actinomycotic liver abscess was diagnosed in a 35-year-old alcoholic farmer from
      southern India with tender hepatomegaly and fever. CT of the abdomen revealed
      three coalescing hypodense lesions in the liver. The causative organism could be
      demonstrated on direct microscopy and cultured from the pus. Treatment with i.v.
      penicillin for 2 months and oral ampicillin for 5 months resulted in cure as
      evidenced by clinical improvement and radiological disappearance of the lesions.

PMID- 16102791
TI  - Factors associated with tuberculosis treatment default and completion at the
      Effia-Nkwanta Regional Hospital in Ghana.
AB  - The level of defaulting from treatment among tuberculosis (TB) patients at the
      Effia-Nkwanta Regional Hospital between January 2000 and December 2001 was 13.9%.
      This study was therefore designed to assess factors associated with TB treatment
      default and completion at the hospital. The initial part of the study consisted
      of three separate focus group discussions for health workers, defaulters and non
      defaulters. The information collected was used to design a questionnaire that was
      administered to defaulters and non-defaulters selected from the Institutional TB
      Register. Univariate logistic regression analysis was performed to identify
      significant factors associated with treatment default. Statistical significance
      was taken as P < 0.05. Default from treatment was significantly associated with
      income per month (P = 0.03), ability to afford supplementary drugs (P = 0.008),
      availability of social support (P = 0.005) and problems relating with others
      while on treatment (P = 0.01). A cordial relationship between patients and health
      staff was the main motivating factor for completion of treatment, whilst
      financial difficulty was the main reason for defaulting from treatment.
      Determination of the characteristics found to be associated with defaulting in
      this study among TB patients at the start of treatment may be helpful in
      improving compliance among patients registered for treatment at the hospital.

PMID- 16102792
TI  - The role of upstream U3 sequences in HIV-1 replication and CD4+ T cell depletion
      in human lymphoid tissue ex vivo.
AB  - The LTRs of all primate lentiviruses contain long U3 regions overlapping the nef
      gene. To assess the relevance of the modulatory U3 region for HIV-1 replication,
      we inactivated the T-rich region, the Polypurine tract and attachment (att)
      sequences in nef by silent mutations and inserted intact cis-regulatory elements
      just upstream of the core enhancer. These modifications severely truncated the U3
      region and eliminated the nef overlap. The resulting HIV-1 mutants expressed
      functional Nef, replicated efficiently and caused CD4+ T cell depletion in ex
      vivo-infected lymphoid tissue suggesting that the modulatory U3 region might not
      be essential for efficient HIV-1 gene expression and AIDS pathogenesis.

PMID- 16102793
TI  - Characterization of murine gammaherpesvirus 68 v-cyclin interactions with
      cellular cdks.
AB  - All known gamma2-herpesviruses encode a cyclin homolog with significant homology
      to mammalian D-type cyclins. The murine gammaherpesvirus 68 (gammaHV68) viral
      cyclin (v-cyclin) has been shown to be oncogenic when expression is targeted to
      thymocytes in transgenic mice and to be critical for virus reactivation from
      latency. Here, we investigate the interaction of the gammaHV68 v-cyclin with
      cellular cyclin-dependent kinases (cdks). We show that, in contrast to the
      Kaposi's sarcoma-associated herpesvirus (KSHV) v-cyclin, the gammaHV68 v-cyclin
      preferentially interacts with cdk2 and cdc2 but does not interact with either
      cdk4 or cdk6. Mutation of conserved residues, predicted to be involved in cdk
      binding based on the gammaHV68 v-cyclin:cdk2 crystal structure, resulted in the
      loss of both cdk binding and the ability to mediate phosphorylation of
      substrates. Like the KSHV v-cyclin, the gammaHV68 v-cyclin appears to confer
      expanded substrate specificity to the cellular cdk binding partners. As expected,
      the gammaHV68 v-cyclin:cdk complexes are able to target phosphorylation of
      histone H1, the retinoblastoma protein (pRb), and p27(Kip1) as assessed using in
      vitro kinase assays. Notably, hyperphosphorylation of pRb was observed during wt
      gammaHV68 replication in serum-starved murine fibroblasts, but not in cells that
      were either mock-infected or infected with a v-cyclin null gammaHV68. In
      addition, infection of serum-starved murine fibroblasts also results in a v
      cyclin-dependent increase in cdk2-associated kinase activity and a concomitant
      decrease in the levels of p27(Kip1). Taken together, the latter studies served to
      validate the results of the in vitro kinase assays. Finally, in vitro kinase
      assays revealed that the gammaHV68 v-cyclin:cdk complexes can also phosphorylate
      p21(Cip1), Bcl-2, and p53. The latter suggests that, at least in vitro, the
      gammaHV68 v-cyclin exhibits functional characteristics of both cyclin E and
      cyclin A.

PMID- 16102794
TI  - A combination of mutations enhances the neurotropism of AAV-2.
AB  - There is strong interest in developing practical strategies for gene delivery to
      the central nervous system (CNS). Direct delivery into the brain or spinal cord
      is highly invasive as well as inefficient or hazardous using most current vector
      systems. Our objective was to generate innocuous gene vehicles that would be
      effectively taken up by axons and then home to the neuron cell bodies. Vectors
      derived from Adeno-Associated Virus (AAV), a harmless human parvovirus, offer
      strong starting candidates for deriving such vehicles. Enhancing the axonal
      uptake of AAV, and conferring more efficient retrograde transport capabilities
      upon the virus, should produce near ideal gene transfer vehicles for the CNS. To
      enhance retrograde transport of the virus, peptides mimicking binding domains for
      cytoplasmic dynein were inserted in the capsid by directed mutagenesis. In
      separate clones, peptides derived from an NMDA receptor antagonist were also
      introduced to provide a specific affinity for this receptor. When combined, these
      two functionally distinct classes of mutation enabled efficient gene transfer
      into neurons under conditions not permissive for standard AAV-2 vectors prepared
      under the same conditions. These results hold strong promise for the development
      of safe, convenient vehicles to target genes and other sequences to neurons,
      enabling new and novel approaches for the treatment of multiple neurological
      disorders.

PMID- 16102795
TI  - Monocular texture segmentation and proto-rivalry.
AB  - When the right eye's target is the left eye's distracter and vice versa,
      orientation-defined search is impossible unless, as we show here, the elements
      are close together. More than 1s was required to find inverse-cyclopean texture
      boundaries when elements were arranged on a 16 x 16 grid. Less than 250 ms was
      required for a 24 x 24 grid covering the same area. The conventional view is that
      binocular rivalry requires at least 200 ms to develop, but our results suggest a
      more rapid access to monocular signals. We call this rapid form of access "proto
      rivalry."

PMID- 16102796
TI  - Perceptual pairing of colour and motion.
AB  - Observers often pair colours with earlier periods of motion. This observation has
      prompted the proposal that changes in colour are processed faster and perceived
      as occurring before physically coincident changes in direction--a brain-time
      account. Alternatively, it has been proposed that the sudden onset of a surface,
      or a direction reversal within a persistent surface, can trigger an analysis that
      determines the perceptual properties of the surface. Hypothetically, this
      analysis persists for some period of time and the consequences are perceived as
      having occurred when the analysis commenced--a post-dictive account. Hypotheses
      based upon these alternate accounts are contrasted in a series of experiments. It
      is shown that the optimal conditions for pairing specific combinations of colour
      and motion arise when colour changes are delayed relative to direction changes.
      In these conditions observers can pair more rapid oscillations of colour and
      motion and perceptual pairings are more systematic relative to when the changes
      in colour and direction are physically synchronous. It is also shown that, when
      pairing colour and motion, the sudden onset of a moving surface does not have the
      same consequences as a direction reversal within a persistent surface. These
      findings are consistent with the brain-time, but are inconsistent with the post
      dictive, account of perceptual asynchrony.

PMID- 16102797
TI  - Phenomenal regression to the frontal and natural picture.
AB  - The retinal image of a figure on a slanted picture is narrower than that of a
      figure on a frontal picture. In this study, the perceived width of various
      figures (horizontal line segments, ellipses, faces, symbolic faces, and artistic
      pictures) on a slanted picture plane was measured. The width of the figures was
      magnified or reduced in order to vary the naturalness of the original figures.
      The perceived width was found to be much closer to the width of the original
      figures than to the retinal images of the slanted figures. The width of the
      original figures was also found to affect the perceived width of the slanted
      figures; the perceived width was observed to be more biased toward a more natural
      width. On the other hand, the naturalness of the figures did not affect the
      perceived slant. These results suggest that the visual system corrected the width
      of the figures on a slanted plane, taking into the account naturalness or
      pragnanz as well as the slant.

PMID- 16102798
TI  - Is the direction of second-order, contrast-defined motion patterns visible to
      standard motion-energy detectors: a model answer?
AB  - Previous psychophysical studies (e.g., Smith & Ledgeway, 1997) have provided
      evidence that under some conditions, the detection of a particular class of
      stimuli (contrast-modulated static noise) widely employed to study second-order
      motion processing may be inadvertently based on encoding local imbalances in
      luminance motion energy. In particular when static noise composed of relatively
      large noise elements is used, direction-identification performance at threshold
      may actually be mediated by the same mechanisms that respond to first-order
      motion, due to the presence of persistent spatial clusters of noise elements of
      the same polarity. However, Benton and Johnson (1997) modeled the responses of
      conventional motion-energy detectors to contrast-modulated static noise patterns
      and found no evidence of any systematic directional biases in such stimuli when
      the mean opponent motion energy was used to quantify performance. In the present
      paper we sought to resolve this discrepancy and show that the precise manner in
      which computational models are implemented is crucial in determining their
      response to contrast-modulated, second-order motion patterns. In particular we
      demonstrate that by considering the information encapsulated by the peak (rather
      than the mean) opponent motion energy and the predominantly local nature of
      imbalances in motion energy that can arise in contrast-modulated static noise, it
      is possible to readily model the patterns of empirical results found.

PMID- 16102799
TI  - Comparison of the accommodation theories of Coleman and of Helmholtz by finite
      element simulations.
AB  - PURPOSE: The accommodation process of the human eye is still a controversial
      subject. Coleman assumes that the lens, together with the zonula fibers, forms a
      diaphragm which is held in a catenary shape due to the pressure difference
      between the aqueous and vitreous body of the lens. The aim of the paper is to
      compare the results of two simulations (according to the Helmholtz and to the
      Coleman theories) with ultrasonographic data. METHODS: An axisymmetric static
      finite element model of the lens was generated using the literature data for
      geometry, material properties and loads. The refractive power of the lens was
      calculated for two different ages (29 and 45 years). RESULTS: The application of
      a pressure to the posterior lens surface did not yield an increase in refractive
      power change during accommodation. Rather a decrease in accommodation related
      refractive power was found. CONCLUSIONS: Physiologically relevant refractive
      power changes are obtained by a simulation in accordance with the Helmholtz
      theory. A simulation in accordance with the Coleman theory does not yield
      physiological values of refractive power change.

PMID- 16102800
TI  - Analgesic synergism between intrathecal morphine and cyclooxygenase-2 inhibitors
      in mice.
AB  - The analgesic effects of the intrathecal coadministration of morphine with
      nimesulide, meloxicam and parecoxib, preferential cyclooxygenase-2 (COX-2)
      inhibitors, were studied in mice using a chemical model of visceral pain, the
      acetic acid writhing test. Isobolographic analysis was used to characterize the
      interactions between mixtures of morphine with each non-steroidal anti
      inflammatory drug. Antinociception dose-response curves were analyzed to obtain
      the ED50's of each drug. A dose response curve for fixed ratio mixtures of
      morphine with COX-2 inhibitors was then performed and the observed ED50's were
      plotted on a two-dimensional isobologram. All the combinations tested showed
      synergistic interactions and the strength of the interaction was ranked as:
      morphine/parecoxib>morphine/meloxicam>morphine nimesulide. The results
      demonstrate that the intrathecal coadministration of COX-2 inhibitors
      significantly enhance morphine-induced antinociception and could result in an
      opioid sparing action which may be useful in the clinical treatment of severe
      pain. A sparing action means that less opioids have to be administered to obtain
      a given analgesic effect. Since intrathecal morphine is often used in clinical
      pain situations, the opioid sparing effect resulting from the synergy observed
      with the coadministration of COX-2 inhibitors may be clinically relevant. One of
      the most significant advantages should be the reduction of opioid toxicity which
      often acts as a major obstacle in pain treatment.

PMID- 16102801
TI  - Effects of sublethal doses of fipronil on the behavior of the honeybee (Apis
      mellifera).
AB  - Fipronil is a phenylpyrazole insecticide introduced for pest control, but it can
      also affect non-target insects such as honeybees. In insects, fipronil is known
      to block GABA receptors and to inhibit ionotropic glutamate-gated chloride
      channels, but the behavioral effects of low doses are not yet fully understood.
      We have studied the effect of sublethal doses of fipronil on the behavior of the
      honeybee (Apis mellifera) under controlled laboratory conditions. The drug was
      either administered orally or applied topically on the thorax. A significant
      reduction of sucrose sensitivity was observed for the dose of 1 ng/bee 1 h after
      a thoracic application. No significant effect on sucrose sensitivity was obtained
      with acute oral treatment. A lower dose of fipronil (0.5 ng/bee applied
      topically) impaired the olfactory learning of the honeybees. By contrast,
      locomotor activity was not affected. Our results suggest a particular
      vulnerability of the olfactory memory processes and sucrose perception to
      sublethal doses of fipronil in the honeybee.

PMID- 16102802
TI  - Perceived risk for developing stroke among older adults.
AB  - BACKGROUND: Persons who perceive their risk for stroke accurately may be more
      likely to engage in prevention practices to reduce their risk. METHODS: In 2004,
      800 adults aged 45 years and older in two counties participated in a telephone
      survey to assess their perceived risk for stroke and their history of stroke risk
      factors. RESULTS: Overall, 39% of respondents perceived themselves to be at risk
      for having a stroke. In the multivariate analyses, younger age, current smoking,
      and a history of diabetes, high blood pressure, high cholesterol, heart disease,
      and stroke/TIA were independently associated with perceived risk for stroke.
      Respondents with atrial fibrillation were no more likely to report being at risk
      for stroke compared to respondents without atrial fibrillation. Perceived risk
      for stroke increased as the number of risk factors increased. However, 46% of
      respondents with three or more risk factors did not perceive themselves to be at
      risk. CONCLUSIONS: Many adults with multiple risk factors do not perceive
      themselves to be at risk for stroke. Clinical and public health efforts are
      needed to increase awareness of the risk for stroke.

PMID- 16102803
TI  - Quantitative neurosyntactic analyses: the final word?

PMID- 16102804
TI  - Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging.
AB  - Mitochondrial oxidative decay, which is a major contributor to aging, is
      accelerated by many common micronutrient deficiencies. One major mechanism is
      inhibition of the pathway of heme biosynthesis in mitochondria, which causes a
      deficit of heme-a. Heme-a, only found in Complex IV, is selectively diminished,
      resulting in oxidant leakage and accelerated mitochondrial decay, which leads to
      DNA damage, neural decay, and aging. We emphasize those deficiencies, which
      appear to cause damage through this mechanism, particularly minerals such as iron
      (25% of menstruating women ingest <50% of the RDA) or zinc (10% of the population
      ingest <50% of the RDA). Several vitamin deficiencies, such as biotin or
      pantothenic acid, also increase mitochondrial oxidants through this mechanism.
      Additionally, other minerals such as magnesium and manganese that play a role in
      mitochondrial metabolism, but do not affect heme directly, are discussed. An
      optimum intake of micronutrients could tune up metabolism and give a marked
      increase in health, particularly for the poor, elderly, and obese, at little
      cost.

PMID- 16102805
TI  - Iron, oxidative stress and human health.
AB  - The amount of iron within the cell is carefully regulated in order to provide an
      adequate level of the micronutrient while preventing its accumulation to toxic
      levels. Iron excess is believed to generate oxidative stress, understood as an
      increase in the steady state concentration of oxygen radical intermediates. The
      main aspects of cellular metabolism of iron, with special emphasis on the role of
      iron with respect to oxidative damage to lipid membranes, are briefly reviewed
      here. Both in vitro and in vivo models are examined. Finally, a discussion of
      iron overload and its impact on human health is included. Overall, further
      studies are required to assess more effective means to limit iron-dependent
      damage, by minimizing the formation and release of free radicals in tissues when
      the cellular iron steady state concentration is increased either as a consequence
      of disease or by therapeutic iron supplementation.

PMID- 16102806
TI  - Changes in denaturation and rheological properties of collagen-hyaluronic acid
      scaffolds as a result of temperature dependencies.
AB  - This report describes the effect of temperature on the mechanical viscoelastic
      properties such as: storage modulus (E'), loss modulus (E''), and loss tangent
      (tandelta) of the collagen sponges modified with hyaluronic acid (HA). In order
      to detect collagen-HA copolymer denaturation and to assess its thermal stability,
      the differential scanning calorimetry (DSC) supplemented by thermogravimetric
      (TG) measurements was used. The denaturation temperature (T(d)) of unmodified
      collagen samples increased from 69 to 86 degrees C for cross-linked samples,
      respectively. These temperature dependencies show remarkable changes in E' and
      E'' at selected temperature up to 226 degrees C for all samples due to the
      release of loosely and strongly bound water. The influence of HA on the
      viscoelastic behavior of collagen is manifested by a shift of the tandelta peak
      associated with the process of decomposition towards higher temperatures
      resulting in a higher thermo-stability of the modified scaffolds.

PMID- 16102807
TI  - Conformational polymorphism, stability and aggregation in spider dragline silks
      proteins.
AB  - Spider silk is spun in a complex and unique process, thought to depend on a
      hydrophobic conversion of a predominantly disordered to a beta-sheet rich protein
      structures. To test this hypothesis we monitored the effect of cationic (DOTAC)
      and anionic (alkyl sulfate) detergents and of (ii) solvent polarity using a
      series of alcohols on the secondary structure transition in dilute solutions of
      native spidroin. Our results showed that the detergents hydrophilic head charge
      and hydrophobic tail length cooperatively induced either a transition to the beta
      sheet rich form or a stable helical state. Changing the solvent polarity showed
      that HFIP and TFE induced formation of stable helical forms whereas MeOH, EtOH
      and IsoP induced a kinetically driven formation of beta-sheet rich structure.

PMID- 16102808
TI  - Effects of paraoxon and ethylparathion on choline oxidase from Alcaligenes
      species: inhibition and denaturation.
AB  - The kinetics and thermodynamics of the effects of paraoxon (POX) and
      ethylparathion (EPA) on choline oxidase (ChOx) were studied. Lineweaver-Burk
      plots of initial velocity data showed a parallel pattern indicating uncompetitive
      inhibition versus choline. The inhibition constant (K(I)) obtained from the
      secondary plots for POX and EPA were 0.14+/-0.01 and 0.48+/-0.05 mM,
      respectively, suggesting that POX is a more potent inhibitor of ChOx than EPA. UV
      absorption was used to monitor the denaturation of ChOx by POX and EPA. A
      decrease in FAD fluorescence associated with the interaction of POX and EPA with
      ChOx suggested a tertiary structural change. Interaction of the enzyme molecule
      with POX or EPA resulted in inhibition and subsequently denaturation of the
      enzyme. The results indicate that inhibition and denaturation of the enzyme by
      POX and EPA are linked, but not parallel events, with inhibition occurring at
      lower concentrations with respect to denaturation. This suggests that the loss of
      initial velocity of the enzyme is an active site specific effect and not due to
      global conformational changes induced by the inhibitors.

PMID- 16102809
TI  - Effects of calcium binding on the structure and stability of human growth
      hormone.
AB  - Thermodynamic analysis of calcium ions binding to human growth hormone (hGH) was
      done at 27 degrees C in NaCl solution, 50 mM, using different techniques. The
      binding isotherm for hGH-Ca2+ was obtained by two techniques of ionmetry, using a
      Ca(2+)-selective membrane electrode, and isothermal titration calorimetry.
      Results obtained by two ionmetric and calorimetric methods are in good agreement.
      There is a set of three identical and non-interacting binding sites for calcium
      ions. The intrinsic dissociation equilibrium constant and the molar enthalpy of
      binding are 52 microM and -17.4 kJ/mol, respectively. Temperature scanning UV-vis
      spectroscopy was applied to elucidate the effect of Ca2+ binding on the protein
      stability, and circular dichroism (CD) spectroscopy was used to show the
      structural change of hGH due to the metal ion interaction. Calcium ions binding
      increase the protein thermal stability by increasing of the alpha helix content
      as well as decreasing of both beta and random coil structures.

PMID- 16102810
TI  - Experimental study on anticoagulant and antiplatelet aggregation activity of a
      chemically sulfated marine polysaccharide YCP.
AB  - A polysaccharide YCP was prepared from a marine filamentous fungus Keissleriella
      sp. YS4108, which exhibited as a molecular weight (Mw) of 2.4x10(3) kDa and its
      three sulfated derivatives (YCP-SL, YCP-SM and YCP-SH) were synthesized, the
      degree of substitution (DS) of which were determined to be 0.13, 0.99 and 1.3,
      with the average molecular weight 0.64x10(3), 0.57x10(3) and 0.45x10(3) kDa,
      respectively. Anticoagulant activity and antiplatelet aggregation activity of
      these sulfated derivates were evaluated by activated partial thromboplastin time
      (APTT), prothrombin time (PT), thrombin time (TT) and platelet aggregation assay.
      The results showed that YCP sulfates significantly prolonged APTT, TT and PT. The
      derivates showed no effects on thrombin in the presence or in the absence of
      antithrombin III (AT III) or heparin cofactor II (HC II), while the derivates
      effectively inhibited factor Xa in the presence of AT III. At the same time, YCP
      SH also possessed potent antiplatelet aggregation activity in vitro compared with
      aspirin. YCP sulfates specifically interfered with different stages of the
      coagulation cascade, and the anticoagulant activity improved with the increasing
      DS and decreased Mw.

PMID- 16102811
TI  - Tannic acid mimicking dendrimers as small intestine submucosa stabilizing
      nanomordants.
AB  - Chemical stabilization resulting in increased resistance to proteolytic
      degradation is one of the approaches in prevention of post-implantational
      aneurysm development in decellularized natural vascular scaffolds. Recently,
      tannic acid (TA) and tannic acid mimicking dendrimers (TAMD) have been suggested
      as potential stabilization agents for collagen and elastin. The aim of this work
      was to determine the stabilizing effects of TAMD on decellularized natural
      scaffolds. Vascular scaffolds fabricated from small intestine submucosa (SIS) and
      SIS plane sheets (Cook Biotech Inc.) were used. The biomechanical properties of
      the SIS vascular graft segments treated with TA and TAMD were tested. The effect
      of TAMD treatment on resistance to proteolytic degradation was evaluated by
      measuring biomechanical properties of TAMD stabilized and non-stabilized SIS
      specimens after incubation in collagenase solution. It was shown that treatment
      with TA as well as with TAMD increased the strength of tubular SIS as well as
      their resistance to proteolytic biodegradation manifested by preservation of
      biomechanical properties after collagenase treatment. Transmission electron
      microscopy demonstrated that treatment with TAMD increased the periodical pattern
      typical of collagen fiber ultrastructure as a result of the "mordant" effect. The
      possible collagen cross-linking effect of TAMD on SIS was investigated by
      differential scanning calorimetry (DSC). The treatment with TAMD induced a small,
      but detectable cross-linking effect, suggesting that TAMD do not establish
      extensive covalent cross links within the extracellular matrix but rather
      interact with collagen, thus rendering SIS scaffolds more resistant to
      proteolytic degradation.

PMID- 16102812
TI  - Optimising bioactive glass scaffolds for bone tissue engineering.
AB  - A 3D scaffold has been developed that has the potential to fulfil the criteria
      for an ideal scaffold for bone tissue engineering. Sol-gel derived bioactive
      glasses of the 70S30C (70 mol% SiO2, 30 mol% CaO) composition have been foamed to
      produce 3D bioactive scaffolds with hierarchical interconnected pore morphologies
      similar to trabecular bone. The scaffolds consist of a hierarchical pore network
      with macropores in excess of 500 microm connected by pore windows with diameters
      in excess of 100 microm, which is thought to be the minimum pore diameter
      required for tissue ingrowth and vasularisation in the human body. The scaffolds
      also have textural porosity in the mesopore range (10-20 nm). The scaffolds were
      sintered at 600, 700, 800 and 1000 degrees C. As sintering temperature was
      increased to 800 degrees C the compressive strength increased from 0.34 to 2.26
      MPa due to a thickening of the pore walls and a reduction in the textural
      porosity. The compressive strength is in the range of that of trabecular bone (2
      12 MPa). Importantly, the modal interconnected pore diameter (98 microm) was
      still suitable for tissue engineering applications and bioactivity is maintained.
      Bioactive glass foam scaffolds sintered at 800 degrees C for 2 h fulfill the
      criteria for an ideal scaffold for tissue engineering applications.

PMID- 16102813
TI  - Characterization of non-neuronal elements within fibronectin mats implanted into
      the damaged adult rat spinal cord.
AB  - Previous studies have shown that mats made from fibronectin (FN) integrate well
      into spinal cord lesion sites and support extensive axonal growth. Using
      immunohistochemistry, we have investigated the non-neuronal factors that
      contribute to these properties. Extensive vascularization was observed in FN mats
      by 1 week along with heavy macrophage infiltration by 3 days post-implantation.
      By 1 week post-implantation, laminin tubules had formed and were associated with
      axons and p75 immunoreactive Schwann cells. By 4 weeks post-implantation, most
      axons were associated with Schwann cell derived myelin. Few oligodendrocytes were
      present within the mat, even with an increase in the number of oligodendrocyte
      precursors around the implant site by 7 days post-implantation. Astrocyte
      proliferation also occurred in the intact tissue, with a prominent glial scar
      forming around the implant within 4 weeks. However, by 2 months post-implantation
      astrocytes were present in the FN implant site and were intermingled with the
      axons. Axonal ingrowth and integration of the FN mats is probably due to the
      ability of FN mats to support and organize infiltration of Schwann cells and
      deposition of laminin. At later time points, myelinated axons remain in the
      implant site, even after other elements (e.g. macrophages and laminin) have
      disappeared. Both of these properties are likely to be important in the design of
      biomaterial bridges for CNS regeneration.

PMID- 16102814
TI  - Construction and enzymatic degradation of multilayered poly-l-lysine/DNA films.
AB  - The layer-by-layer (LbL) self-assembly of poly-l-lysine (PLL) and
      deoxyribonucleic acid (DNA) was used to construct the enzymatic biodegradable
      multilayered films. The LbL build up of DNA multilayers was monitored by UV-vis
      spectrometry, and atomic force microscopy (AFM). AFM, UV-vis spectrometry and
      fluorescence spectrometry measurements indicated that 90% of DNA within the films
      was released almost linearly under 5 U mL(-1)alpha-chymotrypsin in PBS at 37
      degrees C in 35 h. TEM and zeta potential experiments revealed that the released
      DNA molecules were condensed into the slight positive complexes with size from 20
      to several hundred nanometers. The well-structured, easy processed enzymatic
      biodegradable multilayered film may have great potential for gene applications in
      tissue engineering, medical implants, etc.

PMID- 16102815
TI  - Poly (D,L-lactic acid) macroporous guidance scaffolds seeded with Schwann cells
      genetically modified to secrete a bi-functional neurotrophin implanted in the
      completely transected adult rat thoracic spinal cord.
AB  - Freeze-dried poly(D,L-lactic acid) macroporous scaffold filled with a fibrin
      solution containing Schwann cells (SCs) lentivirally transduced to produce and
      secrete D15A, a bi-functional neurotrophin with brain-derived neurotrophic factor
      and neurotrophin-3 activity, and to express green fluorescent protein (GFP) were
      implanted in the completely transected adult rat thoracic spinal cord. Control
      rats were similarly injured and then implanted with scaffolds containing the
      fibrin solution with SCs lentivirally transduced to produce express GFP only or
      with the fibrin solution only. Transgene production and biological activity in
      vitro, SC survival within the scaffold in vitro and in vivo, scaffold
      integration, axonal regeneration and myelination, and hind limb motor function
      were analyzed at 1, 2, and 6 weeks after implantation. In vitro, lentivirally
      transduced SCs produced 87.5 ng/24 h/10(6) cells of D15A as measured by
      neurotrophin-3 activity in ELISA. The secreted D15A was biologically active as
      evidenced by its promotion of neurite outgrowth of dorsal root ganglion neurons
      in culture. In vitro, SCs expressing GFP were present in the scaffolds for up to
      6 h, the end of a typical surgery session. Implantation of SC-seeded scaffolds
      caused modest loss of spinal nervous tissue. Reactive astrocytes and chondroitin
      sulfate glycosaminoglycans were present in spinal tissue adjacent to the
      scaffold. Vascularization of the scaffold was ongoing at 1 week post
      implantation. There were no apparent differences in scaffold integration and
      blood vessel formation between groups. A decreasing number of implanted (GFP
      positive) SCs were found within the scaffold during the first 3 days after
      implantation. Apoptosis was identified as one of the mechanisms of cell death. At
      1 week and later time points after implantation, few of the implanted SCs were
      present in the scaffold. Neurofilament-positive axons were found in the scaffold.
      At 6 weeks post-grafting, myelinated axons were observed within and at the
      external surface of the scaffold. Axons did not grow from the scaffold into the
      caudal cord. All groups demonstrated a similar improvement of hind limb motor
      function. Our findings demonstrated that few seeded SCs survived in vivo, which
      could account for the modest axonal regeneration response into and across the
      scaffold. For the development of SC-seeded macroporous scaffolds that effectively
      promote axonal regeneration in the injured spinal cord, the survival and/or total
      number of SCs in the scaffold needs to be improved.

PMID- 16102816
TI  - Atelocollagen for culture of human nucleus pulposus cells forming nucleus
      pulposus-like tissue in vitro: influence on the proliferation and proteoglycan
      production of HNPSV-1 cells.
AB  - Nucleus pulposus (NP) is responsible for maintaining function and structure of
      the disc. Scaffolds to culture disc cells three-dimensionally are emphasized in
      recent reports on development of a new method for treating disc degeneration
      using cell transplantation and tissue engineering. Among artificial scaffolds and
      cell carrying materials, Atelocollagen is a collagen gel that has an advantage in
      safety issues over others. However, to date there has been no study that
      investigated culture of human nucleus pulposus cells in Atelocollagen. To
      investigate whether Atelocollagen could be used as a culture scaffold and if it
      has any effect on cell proliferation and proteoglycan (PG) production, as well as
      to find the optimal commercially available Atelocollagen for NP cell
      transplantation and tissue engineering, we cultured human NP cell line HNPSV-1,
      in three different Atelocollagen and compared with alginate. Furthermore, NP-like
      tissues were generated using these cells and different Atellocollagen solutions.
      Results showed that both DNA synthesis and content is significantly greater when
      cultured in Atelocollagen than in alginate. On the other hand, proteoglycan
      synthesis and accumulation was significantly greater in alginate compared with
      the 0.3% Atelocollagen scaffolds; with 3% Atelocollagen, however, results were
      similar. NP-like tissue generated by Atelocollagen showed good water and
      proteoglycan preservation. The current study demonstrates that the use of
      Atelocollagen as an in vitro culture scaffold for three-dimensional culture of
      human NP cell lines is indeed feasible and moreover, Atelocollagen possesses the
      potential to become a candidate scaffold for cell transplantation or tissue
      engineering for the treatment of intervertebral disc degeneration.

PMID- 16102817
TI  - Influence of three-dimensional scaffold on the expression of osteogenic
      differentiation markers by human dermal fibroblasts.
AB  - Current research in the field of tissue engineering utilizes biomaterial
      scaffolds, cells, and growth factors for the creation of a functional,
      biologically active tissue. This study examined the effect of two commercially
      available, three-dimensional scaffolds, ultraporous beta-tricalcium phosphate
      ceramics (beta-TCP, Vitoss) and open-celled poly(lactic acid) foams (OPLA,
      Drilac), on the osteogenic differentiation potential of human dermal fibroblasts.
      Serum-free, chemically-defined medium containing the metabolic factor 1alpha,25
      dihydroxyvitamin D3 was used to promote an osteogenic phenotype in these cells.
      Osteoblast differentiation was assessed using PCR and immunohistochemical methods
      to detect gene and protein expression for the osteoblast markers alkaline
      phosphatase, osteopontin, and osteocalcin. Dermal fibroblasts cultured on beta
      TCP scaffolds in chemically-defined medium with vitamin D3 exhibited up-regulated
      gene and protein expression compared to cells cultured on OPLA scaffolds. These
      results suggest that Vitoss (beta-TCP) scaffolds seeded with dermal fibroblasts
      and maintained in chemically-defined medium with vitamin D3 are better suited for
      bone tissue engineering applications than Drilac (OPLA) foams.

PMID- 16102818
TI  - Anterior spinal column augmentation with injectable bone cements.
AB  - A vertebral fracture, whether originating from osteoporosis or trauma, can be the
      cause of pain, disability, deformation and neurological deficit. The treatment of
      vertebral compression fractures has, for many years until the advent of
      vertebroplasty, consisted of bedrest and analgesics. Vertebroplasty is a
      percutaneous technique during which bone cement is injected in a vertebral body
      to provide immediate pain relief by stabilization. Inflatable bone tamps can,
      prior to the injection of cement, be used to create a void in the vertebral body,
      in which case the technique is known as balloon vertebroplasty (or kyphoplasty).
      The chance of extracorporal cement leakage is smaller for balloon vertebroplasty
      than for vertebroplasty. Some authors also claim to have gained some correction
      in vertebral body height or angulation. Both interventions can be used for
      several indications, including osteoporotic compression fractures and osteolytic
      lesions of the vertebral body such as myeloma, hemangioma or metastasis, and also
      for traumatic burst fractures in combination with pedicle screw instrumentation.
      Polymethyl methacrylate cement is the bone void filler that is used most
      frequently, although the application of calcium phosphate cements has been
      studied widely in vitro, in vivo and also in small-scale clinical series. The
      clinical results of (balloon-) vertebroplasty are favorable with 85-95% of all
      patients experiencing immediate and long-lasting relief of pain. Serious
      complications are relatively rare but include neurological deficit and pulmonary
      embolism. In this paper, both vertebroplasty and balloon vertebroplasty and their
      respective indications, techniques and results are described in relation with the
      application and limitations of permanent and resorbable injectable bone cements.

PMID- 16102819
TI  - Synthesis and characterizations of biodegradable and crosslinkable poly(epsilon
      caprolactone fumarate), poly(ethylene glycol fumarate), and their amphiphilic
      copolymer.
AB  - A series of self-crosslinkable and biodegradable polymers, poly(caprolactone
      fumarate) (PCLF), poly(ethylene glycol fumarate) (PEGF), and their copolymer PEGF
      co-PCLF, has been developed for tissue engineering applications using a novel
      synthesis method. The current method employs potassium carbonate (K2CO3), other
      than the previously reported triethylamine, as the proton scavenger. The new
      synthetic route is more convenient and less time-consuming to carry out, and the
      synthesized polymers have a much lighter color, which renders them more suitable
      for self-crosslinking via photo-initiation. This group of polymers are
      essentially copolymers of fumaryl chloride, which contains double bonds for in
      situ crosslinking, with poly(epsilon-caprolactone) (PCL) or/and poly(ethylene
      glycol) (PEG) that has a flexible chain to facilitate self-crosslinking. Both
      PCLF and PEGF, and their amphiphilic copolymer PEGF-co-PCLF could be self
      crosslinked or photocrosslinked to produce scaffolds without the use of a
      crosslinking agent. Our results suggest that these polymers are potentially
      useful as injectable, self-crosslinkable, and photo-crosslinkable materials for
      diverse tissue engineering applications.

PMID- 16102820
TI  - Molecular aspects of rapid, reversible, Ca2+-dependent de-phosphorylation of
      pp63/parafusin during stimulated exo-endocytosis in Paramecium cells.
AB  - Ca2+ signalling governs stimulated exocytosis and exocytosis-coupled endocytosis
      also in Paramecium cells. Upon stimulation, the < or =10(3) dense-core exocytotic
      organelles (trichocysts) can be synchronously (80 ms) released, followed by
      endocytotic membrane resealing (350 ms) and retrieval. Paramecium is the most
      synchronous dense-core exocytotic system known, allowing to dissect rapidly
      reversible Ca2+-dependent phenomena. This holds for the reversible de-/re
      phosphorylation cycle of a 63 kD phosphoprotein, pp63/parafusin (pf), which we
      have cloned, immuno-localised, and characterised as phosphoglucomutase, the
      enzyme funneling glucose into the glycolytic pathway. It was isolated ex vivo,
      followed by MALDI analysis, while X-ray structure analysis was performed after
      heterologous expression. We found multiple phosphorylation of superficial Ser/Thr
      residues. Although present also in exo(-) mutants, pp63/pf is selectively de
      phosphorylated only in exo(+) strains during synchronous exocytosis (80 ms) and
      re-phosphorylated within approximately 20 s, i.e., the time required to re
      establish [Ca2+] homeostasis. We have isolated relevant protein phosphatases and
      kinases and probed their activity on pp63/pf in vitro. We consider
      Ca2+/calmodulin-activated PP2B (calcineurin, whose subunits have been cloned)
      relevant for de-phosphorylation. Re-phosphorylation can be achieved by two
      protein kinases that also have been cloned. One is activated by cGMP (PKG) which
      in turn is formed by Ca2+-activated guanylate cyclase. Another kinase, casein
      kinase 2, is inhibited by Ca2+ and, hence, activated with some delay in parallel
      to decreasing [Ca2+] after exocytosis. In total, several Ca2+-sensitive cycles
      cooperate whose protein components have been localised to the cell cortex.
      Regulation of the phosphorylation degree of pp63/pf may affect structure binding
      on a microscale and/or its enzymatic activity. All this may serve fueling
      substrate into glycolysis with increased ATP re-formation (compromised in exo(-)
      mutants) and NADH formation, with effects on Ca2+ signalling including
      mobilisation from cortical stores (alveolar sacs) and overall effects on ATP and
      Ca2+ dynamics during synchronous exo- and endocytosis.

PMID- 16102821
TI  - Exporting calcium from cells.
AB  - All eukaryotic cells import Ca2+ through a number of variously gated plasma
      membrane channels. Once inside cells, Ca2+ transmits information to a large
      number of (enzyme) targets. Eventually, it must be exported again, to prevent the
      overloading of the cytosol with Ca2+. Two systems export Ca2+ from cells: a high
      affinity, low capacity Ca2+-ATPase, and a lower affinity, but much larger
      capacity, Na+/Ca2+ exchanger. The ATPase (commonly called the Ca2+ pump) is the
      fine-tuner of cell Ca2+, as it functions well even if the concentration of the
      ion drops below the microM level. It is a large enzyme, with 10 transmembrane
      domains and a C-terminal cytosolic tail that contains regulatory sites, including
      a calmodulin-binding domain. Four distinct gene products plus a large number of
      splice variants have been described. Some are tissue specific, the isoform 2
      being specifically expressed in the sensorial cells of the Corti organ in the
      inner-ear. Its genetic absence causes deafness in mice. Two different families of
      the Na+/Ca2+ exchanger exist, one of which, originally described in
      photoreceptors, transports K+ and Ca2+ in exchange for Na+. The exchanger is
      particularly active in excitable cells, e.g., heart, where the necessity
      cyclically arises to rapidly eject large amounts of Ca2+. In addition to heart,
      the exchanger is particularly important to neurons: the cleavage of the most
      important neuronal isoform (NCX3) by calpains activated by excitotoxic treatments
      generates Ca2+ overload and eventually cell death.

PMID- 16102822
TI  - How to measure Ca2+ in cellular organelles?
AB  - The review will aim to briefly summarise information on calcium measurements in
      cellular organelles with emphases on studies conducted in live cells using
      optical probes. When appropriate we will try to compare the effectiveness of
      different indicators for intraorganellar calcium measurements. We will consider
      calcium measurements in endoplasmic reticulum, Golgi apparatus,
      endosomes/lysosomes, nucleoplasm, nuclear envelope, mitochondria and secretory
      granules.

PMID- 16102823
TI  - The inositol 1,4,5-trisphosphate receptors.
AB  - The inositol (1,4,5)-trisphosphate receptors (InsP3R) are the intracellular
      calcium (Ca2+) release channels that play a key role in Ca2+ signaling in cells.
      Three InsP3R isoforms-InsP3R type 1 (InsP3R1), InsP3R type 2 (InsP3R2), and
      InsP3R type 3 (InsP3R3) are expressed in mammals. A single InsP3R isoform is
      expressed in Drosophila melanogaster (DmInsP3R) and Caenorhabditis elegans
      (CeInsP3R). The progress made during last decade towards understanding the
      function and the properties of the InsP3R is briefly reviewed in this chapter.
      The main emphasis is on studies that revealed structural determinants responsible
      for the ligand recognition by the InsP3R, ion permeability of the InsP3R,
      modulation of the InsP3R by cytosolic Ca2+, ATP and PKA phosphorylation and on
      the recently identified InsP3R-binding partners. The main focus is on the
      InsP3R1, but the recent information about properties of other InsP3R isoforms is
      also discussed.

PMID- 16102824
TI  - MEL1S, not MEL1, is overexpressed in myelodysplastic syndromes patients with
      t(1;3)(p36;q21).
AB  - Balanced chromosomal translocations rarely occur in myelodysplastic syndromes
      (MDS). We describe here in three further Chinese patients with myelodysplastic
      syndromes (MDS) whose cytogenetic analysis showed t(1;3)(p36;q21). We detected
      the expression pattern of MEL1 and MEL1s in BM of two healthy subjects and the
      three patients, and found that the expression of MEL1s was overexpressed in MDS
      patients with t(1;3)(p36;q21). Our findings combined previous observations
      reported in literature support that MDS patients with t(1;3)(p36;q21) should be a
      new specific subset of MDS. Imbalance of a complete MEL1 message with a PR domain
      and a short MEL1 message lacking a PR domain (MEL1S) might be involved in the
      pathogenesis of these patients.

PMID- 16102825
TI  - Usefulness and prognostic impact on survival of WHO reclassification in FAB low
      risk myelodyplastic syndromes.
AB  - In 1999, WHO proposed a revised classification for myelodysplastic syndromes
      (MDS). According to this system, FAB low risk MDS (RA and RARS) were defined as
      such when the presence of dysplastic features was only restricted to the
      erythroid lineage, and new categories, refractory cytopenia with multilineage
      dysplasia (RCMD) and refractory cytopenia with multilineage dysplasia and ringed
      sideroblasts (RCMD-RS), were added. In a retrospective analysis of 240
      consecutive patients diagnosed at our institution as having FAB RA and RARS, we
      reclassified the disease following the WHO criteria and we found that 179/214
      patients (84%) still remained in the RA category, while 35/214 (16%) moved to
      RCMD. Moreover, 17/26 patients (65%) maintained the RARS diagnosis, whereas 9/26
      (35%) were re-classified as RCMD-RS. We detected differences among the WHO
      subgroups as to age and sex distribution as well as to median survival observed
      by stratifying patients according to different prognostic scoring systems.
      Furthermore we confirmed the usefulness of WHO segregation with regard to its
      predictive value for evolution into acute leukaemia. Our study provides evidence
      that WHO classification may have prognostic impact on MDS subgroups which are
      usually categorized by FAB as having a favourable outcome.

PMID- 16102826
TI  - IgH and TCRgamma gene rearrangements, cyclin A1 and HOXA9 gene expression in
      biphenotypic acute leukemias.
AB  - In this study we investigated IgH and TCRgamma gene rearrangements, cyclin A1 and
      HOXA9 gene expression as well as the in vitro growth of biphenotypic acute
      leukemia (BAL) blasts in relation to acute lymphoblastic leukemia (ALL) and acute
      myeloid leukemia (AML). The aim of the study was to correlate BAL morphology and
      its biological parameters in order to get information that might be used for
      additional stratification of BAL. This rare form of AL was identified in a total
      of 10 patients, comprising 4.3% of adult and 3.0% of pediatric patients with de
      novo AL referred to our institution during the 1999-2003 period. Our results
      indicate that IgH and TCRgamma gene rearrangements correlated well with lymphoid
      BAL morphology, whereas the expression of cyclin A1 correlated with myeloid and
      undifferentiated BAL morphology. Surprisingly, HOXA9 expression, a marker
      associated with myeloid cell lineage, showed no strong correlation with BAL
      morphology. Finally, in vitro growth of blasts during a 7-day culture showed
      autonomous cell growth in 3/10 AML and 3/8 myeloid BAL samples tested, but not in
      any of the AL with lymphoid features. Further studies are needed to confirm these
      findings and to extend research to a broader spectrum of cell markers.

PMID- 16102827
TI  - Defensive behavior.

PMID- 16102828
TI  - Monitoring of the impact of Prestige oil spill on Mytilus galloprovincialis from
      Galician coast.
AB  - In November 2002, the Prestige oil tanker was wrecked in front of Galician coast
      (NW of Spain), spilling near 63,000 tons of heavy oil until February 2003.
      Contamination produced was very extensive (70% of Galician beaches were reached
      by the oil) but heterogeneous, alternating intensely affected zones with
      neighbour locations where the repercussion was minimal. The objective of this
      study was to monitor sea environment contamination caused by Prestige oil spill
      during an 11-month period (August 2003-June 2004, nine samplings) in two
      locations of Galician coast with different geographical properties (Lira and
      Ancoradoiro beaches), by means of chemical determination of total polycyclic
      aromatic hydrocarbons (TPAH) in seawater, and using as exposure biomarker TPAH
      content in mussel (Mytilus galloprovincialis) tissues, and as effect biomarker
      DNA damage in mussel gills, evaluated by the comet assay. In addition, recovery
      ability of the mussels was determined after a 7-day stay in the laboratory. TPAH
      contents in seawater were very high in the earliest samplings, but then they
      maintained below 200 ng L(-)(1), similar to reference seawater. However, TPAH
      levels in mussel tissues were more variable: they increased again from January
      2004, probably due to the adverse meteorological conditions that turned over the
      sea bottom and dispersed the oil accumulated in sediments. In most samplings,
      these levels decreased during the recovery stage. DNA damage in oil-exposed
      mussels was significantly higher than in reference mussels, both before and after
      the recovery phase, but they did not differ to one another. Comet tail length was
      slightly reduced during the recovery stage, indicative of a certain DNA repair in
      exposed mussels. This study showed up the importance of monitoring sea
      contamination events during an extended time, not only in evaluating the presence
      of the contaminants in the environment but also in determining their
      bioaccumulation and their effect on the exposed organisms.

PMID- 16102829
TI  - Cholera toxin induced novel genes in human lymphocytes and monocytes.
AB  - Cholera toxin (CT) is well known as an inducer of the accumulation of cellular
      cAMP through the ADP-ribosylation of the Gs protein by CT. CT is also one of the
      most powerful mucosal adjuvants. However, the molecular mechanisms of the CT
      adjuvanticity are not well understood. Here, the transcriptional responses of
      cultured human lymphocytes and monocytes in response to CT were analyzed using
      differential display-PCR. The full complement of cellular mRNA was examined by
      high resolution polyarylamide gel electrophoresis and sequence analyses of the
      PCR products of 240 primer sets. Over 100 genes with altered expression were
      initially identified. The expressions of 65 of these genes were further analyzed
      and confirmed using custom glass cDNA arrays, RT-PCR and real-time PCR.
      Immunomodulatory genes such as CD2, HIF1, CXCL2, L-plastin, LILR and IFI30 were
      affected by CT. In addition, 14 novel genes with previously unknown functions
      were found to be CT induced. These CT induced gene expression alterations provide
      more insight in the mechanisms of CT actions. The CT induced gene expressions
      alterations could contribute to the CT adjuvanticity.

PMID- 16102830
TI  - High concentrations of therapeutic IgG1 antibodies are needed to compensate for
      inhibition of antibody-dependent cellular cytotoxicity by excess endogenous
      immunoglobulin G.
AB  - A common feature of human IgG1 antibodies used for cancer treatment is that their
      anti-tumour efficacy requires high serum trough levels and continued therapy for
      several months. Treatment cycles, thereby, consume several grams of IgG1
      translating into significant drug needs and costs. The basis for the low in vivo
      efficacy, which is in contrast to high in vitro antibody-dependent cellular
      cytotoxicity (ADCC), is not well understood. Here, we have explored factors
      contributing to this discrepancy using adecatumumab (MT201), a fully human
      monoclonal IgG1 against epithelial cell adhesion molecule (Ep-CAM) and
      trastuzumab (Herceptin), a humanized IgG1 with specificity for the human
      epithelial growth factor receptor type 2 (HER-2) antigen. We found that
      physiological levels of human sera strongly inhibited ADCC of both IgG1
      antibodies. Effects showed some dependence on the density of Ep-CAM and HER-2
      targets, the tumour cell line tested and on effector cell and serum donors.
      Removal of IgG by affinity chromatography abolished the inhibitory effect of a
      serum pool. Inhibition of ADCC was fully restored by adding back the IgG fraction
      or by an equal amount of IgG from a commercial source. We further demonstrate
      that CD56-positive lymphocytes within human PBMC contributed >90% to ADCC and
      that normal serum levels of IgG effectively competed for in vitro binding of an
      IgG1 antibody to low-affinity Fcgamma receptor type III (CD16), as is present on
      natural killer (NK) cells. Competition of serum IgG for binding of therapeutic
      IgG1 to NK cell may be one important reason why high antibody doses are required
      in the clinic for treatment of cancer by an ADCC-based mechanism.

PMID- 16102831
TI  - Alanine scanning mutagenesis of the chemokine receptor CCR3 reveals distinct
      extracellular residues involved in recognition of the eotaxin family of
      chemokines.
AB  - Despite considerable differences in primary structure, the chemokines eotaxin
      1/CCL11, eotaxin-2/CCL24 and eotaxin-3/CCL26 signal via a single receptor, CCR3,
      but exhibit different potencies and efficacies. To examine receptor/ligand
      interactions in more detail, we performed alanine scanning mutagenesis of 21
      charged residues within the extracellular loops (ECLs) of CCR3. Following
      transient expression in the L1.2 cell line, CCR3 mutants were assessed for their
      ability to be expressed at the cell surface, bind CCL11 and induce chemotactic
      responses to CCL11, CCL24 and CCL26. The majority of constructs were well
      expressed at the cell surface and bound CCL11 with low nanomolar affinity.
      Exceptions to this rule included the mutants E175A and E176A (ECL2) which were
      poorly expressed and responded weakly to all three ligands in chemotaxis assays.
      In contrast, the mutants K26 (amino-terminus) E179 and E180 (ECL2) responded in
      chemotaxis assays to CCL11 and CCL24, but not to CCL26. Mutation of residues in
      ECL3 was informative, with the D272A, K277A and D280A mutants exhibiting reduced
      chemotactic responses to two or more of the three ligands examined, despite being
      expressed on the cell surface at levels similar to WT CCR3. This suggests a major
      role for ECL3 in the recognition of all three eotaxins. In summary, distinct
      acidic and basic residues within CCR3 determine both receptor expression and
      activation by the eotaxins. Determining how these chemokines interact with their
      receptor at the molecular level should increase our understanding of the process
      of chemokine receptor activation.

PMID- 16102832
TI  - Heterogeneity of MBL-MASP complexes.
AB  - In order to study aspects of the stoichiometry and composition of human MBL-MASP
      complexes in the population, MBL-MASP complexes were bound from sera of 152
      healthy individuals onto mannan-coated microtitre plates. Bound mannan-binding
      lectin (MBL) was measured by ELISA, and the enzyme activities of MBL-bound MASP-1
      and MASP-2 were measured by an amidolytic assay and a C4 fixation assay,
      respectively. MASP-1 activity correlated with MBL concentration, as did MASP-2
      activity (in both cases: p<0.0001). This is expected since MASP-1 and MASP-2 are
      bound to the mannan via MBL. However, when MASP activities were normalised to MBL
      concentration (i.e. MASP-1 activity/[MBL], MASP-2 activity/[MBL]) MASP-1 activity
      was inversely correlated with MASP-2. This means on average that high MASP-1
      correlates with low MASP-2 and vice-versa, and confirms the hypothesis that
      native MBL-MASP complexes on average do not have fixed MBL-(MASP-1)-(MASP-2)
      stoichiometry. The findings are consistent with separate populations of MBL-MASP
      1 complexes and MBL-MASP-2 complexes, the concentrations of which show wide inter
      individual variation.

PMID- 16102833
TI  - Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered
      twice daily to dry eye disease patients for up to 3 years.
AB  - OBJECTIVE: To evaluate cyclosporine 0.1% ophthalmic emulsion over a 1- to 3-year
      period in moderate to severe dry eye disease patients. DESIGN: Nonrandomized,
      multicenter, open-label clinical trial extending 2 ophthalmic cyclosporine phase
      III clinical trials. PARTICIPANTS: Four hundred twelve patients previously dosed
      for 6 to 12 months with cyclosporine 0.05% or 0.1% in prior phase III trials.
      INTERVENTION: Patients instilled ophthalmic cyclosporine 0.1% twice daily into
      both eyes for up to 3 consecutive 12-month extension periods. MAIN OUTCOME
      MEASURES: Corneal staining, Schirmer tests, and symptom severity assessments were
      conducted during the first 12-month extension, with a patient survey during the
      second 12-month extension. Biomicroscopy and visual acuity (VA) examinations,
      intraocular pressure (IOP) measurements, and adverse effects queries occurred at
      6-month intervals. RESULTS: Mean duration of treatment was 19.8 months.
      Improvements in objective and subjective measures of dry eye disease were modest,
      probably because of prior treatment with cyclosporine. Most survey respondents
      said their symptoms began to resolve in the first 3 months of cyclosporine
      treatment during the previous phase III clinical trials. At study exit, VA
      decreased in 12.6% (93/738) and increased in 5.4% (40/738) of eyes by > or =2
      lines; severity of biomicroscopy findings increased in 3.4% (chemosis; 26/760),
      7.2% (conjunctival hyperemia; 55/760), or 8.5% (tear film debris; 64/756) of
      eyes; and mean IOP increased 0.18 mmHg relative to baseline. The most common
      treatment-related adverse events were burning (10.9% of patients [45/412]),
      stinging (3.9% [16/412]), and conjunctival hyperemia (3.4% [14/412]). No serious
      treatment-related adverse events occurred. Most patients (95.2% [140/147]) said
      they would continue cyclosporine therapy; 97.9% (143/146) would recommend it to
      other dry eye patients. CONCLUSIONS: Therapy of chronic dry eye disease with
      cyclosporine 0.1% ophthalmic emulsion for 1 to 3 years was safe, well tolerated,
      and not associated with systemic side effects. The results supplement the safety
      record of the commercially available cyclosporine 0.05% ophthalmic emulsion.

PMID- 16102834
TI  - Global Rating Assessment of Skills in Intraocular Surgery (GRASIS).
AB  - OBJECTIVE: The American Board of Ophthalmology in conjunction with the
      Accreditation Council for Graduate Medical Education has mandated the systematic
      assessment of surgical competence of ophthalmology residents at all residency
      programs. We present a tool complementary to the Objective Assessment of Skills
      in Intraocular Surgery (OASIS) to assess residents' surgical competence.
      PARTICIPANTS: Twenty experts in resident education, including the chiefs of all
      ophthalmology services and the chief resident at the Harvard Medical School
      Department of Ophthalmology. METHODS: A 1-page subjective evaluation form was
      developed in conjunction with the Objective Assessment of Skills in Intraocular
      Surgery evaluation form to assess the surgical skills of residents. A panel of
      surgeons at the Harvard Medical School Department of Ophthalmology at the
      Massachusetts Eye and Ear Infirmary reviewed the form and provided constructive
      feedback. RESULTS: Experts' comments were incorporated, establishing face and
      content validity. CONCLUSIONS: The Global Rating Assessment of Skills in
      Intraocular Surgery (GRASIS) has face and content validity. It can be used to
      assess a resident's surgical care of patients as well as a resident's surgical
      knowledge, preparedness, and interpersonal skills. Reliability and predictive
      validity will be determined at our institution. We believe the GRASIS evaluation
      form will be a valuable tool in conjunction with the OASIS evaluation form for
      assessing ophthalmology residents' surgical skills at other residency programs as
      well.

PMID- 16102835
TI  - Severe ocular injuries from pointed door handles in children.
AB  - OBJECTIVE: To report severe ocular injuries caused by pointed door handles in
      children. DESIGN: Noncomparative, interventional, retrospective case series.
      METHODS: Clinical records of 15 patients who sustained severe ocular injuries
      from door handles were reviewed for place of trauma, presenting symptoms and
      signs, surgical procedures performed, and final outcome. MAIN OUTCOME MEASURES:
      Trauma caused by complications from the door handle injury, such as loss of
      vision and ocular and adnexal injuries, and treatment rendered. RESULTS: There
      were 12 boys and 3 girls with an average age of 7.8 years (range, 6-10 years).
      Place of trauma was at home in 12 children and in school in 3 children.
      Presenting visual acuity (VA) was 4/200 in 1 patient, light perception (LP) in 5
      patients, and no light perception (NLP) in 9 patients. There were 9 eyelid or
      canalicular lacerations, 4 ruptured globes, and 14 optic nerve avulsions. All
      ruptured globes were repaired initially and eyelid and canalicular lacerations
      were repaired primarily within 24 hours of presentation. Average follow-up was 21
      months (range, 1 month-8 years). Final VA was 20/30 in 1 patient, LP in 1
      patient, and NLP in 13 patients. Eight eyes required enucleation for painful
      blind eye or to achieve optimal cosmesis. CONCLUSIONS: Pointed door handles
      installed at current heights may pose a significant risk of ocular and periocular
      injuries among young children.

PMID- 16102836
TI  - Serum adenosine deaminase enzyme and plasma platelet factor 4 activities in
      active pulmonary tuberculosis, HIV-seropositive subjects and cancer patients.
AB  - The aim of this study was to determine the serum adenosine deaminase (ADA) and
      plasma platelet factor (PF-4) activities in patients with active pulmonary
      tuberculosis, HIV seropositive subjects, cancer patients (acute and chronic type
      lymphoblastic leukaemia) and to compare them with the results of healthy
      individuals. Eighty-eight subjects were enrolled in this study, 24 patients with
      active pulmonary tuberculosis, 20 patients with HIV seropositive subjects, 24
      patients with cancer, 12 patients with acute type lymphoblastic leukaemia, 12
      patients with chronic type lymphoblastic leukaemia) patients and 20 healthy
      individuals. ADA activity was determined in serum samples using colorimetric
      method and plasma PF4 activity was measured by using a sandwich-type enzyme
      immunoassay. When all study groups were compared with the control group, mean
      serum ADA activities were found to be significantly (p<0.01) higher in the sera
      of patients with active pulmonary tuberculosis (median, range: 39 IU/l), HIV
      seropositive subjects (median, range: 31 IU/l) than in the sera of cancer
      patients (median, range: 15) and healthy controls (median, range: 32 IU/l).
      Plasma PF-4 activities in active pulmonary tuberculosis patients (median, range:
      84 IU/ml) were found to be significantly elevated when compared to HIV
      seropositive subjects (median, range: 59 IU/ml), cancer patients (median, range
      55 IU/ml) and healthy individuals (median, range: 56 IU/ml) (p<0.01). Serum ADA
      and plasma PF-4 activities showed significant alteration in patients with active
      pulmonary tuberculosis compared to patients with HIV seropositive subjects,
      cancer patients and healthy individuals. In conclusion, we suggest that serum ADA
      and PF-4 activities can be used in the diagnosis of tuberculosis as an
      supplementary laboratory test in combination with clinical and laboratory
      findings. Further controlled studies are necessary to determine the importance of
      the PF-4 and ADA activities in patients with active pulmonary tuberculosis, HIV
      seropositive subjects and cancer patients.

PMID- 16102837
TI  - Involvement of P2 receptors in the growth and survival of neurons in the CNS.
AB  - Extracellular adenosine 5'-triphosphate (ATP) has been recognized as a
      ubiquitous, unstable signalling molecule, acting as a fast neurotransmitter and
      modulator of transmitter release and neuronal excitability. Recent findings have
      demonstrated that ATP is a growth factor participating in differentiation, cell
      proliferation, and survival, as well as a toxic agent that mediates cellular
      degeneration and death. Potential sources of extracellular purines in the nervous
      system include neurons, glia, endothelium, and blood. A complex family of
      ectoenzymes rapidly hydrolyzes or interconverts extracellular nucleotides,
      thereby either terminating their signalling action or producing an active
      metabolite of altered purinoceptor selectivity. Most effects are mediated through
      the 2 main subclasses of specific cell surface receptors, P2X and P2Y. Members of
      these P2X/Y receptor families are widely expressed in the central nervous system
      (CNS) and are involved in glia-glia and glia-neuron communications, whereby they
      play important physiological and pathophysiological roles in a variety of
      biological processes. After different kinds of "acute" CNS injury (e.g.,
      ischemia, hypoxia, mechanical stress, axotomy), extracellular ATP can reach high
      concentrations, up to the millimolar range, flowing out from cells into the
      extracellular space, exocytotically, via transmembrane transport, or as a result
      of cell damage. In this review, P2 receptor activation as a cause or a
      consequence of neuronal cell activation or death and/or glial activation is
      described. The involvement of P2 receptors is also described under different
      "chronic" pathological conditions, such as pain, epilepsia, toxic influence of
      ethanol or amphetamine, retinal diseases, Alzheimer's disease (AD), and possibly,
      Parkinson's disease. The relationship between changes in P2 receptor expression
      and the specific response of different cell types to injury is extremely complex
      and can be related to detrimental and/or beneficial effects. The present review
      therefore considers ATP acting via P2 receptors as a potent regulator of normal
      physiological and pathological processes in the brain, with a focus on
      pathophysiological implications of P2 receptor functions.

PMID- 16102838
TI  - Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the
      development of specific therapeutic agents.
AB  - Cyclic nucleotide phosphodiesterases (PDEs), which are ubiquitously distributed
      in mammalian tissues, play a major role in cell signaling by hydrolyzing cAMP and
      cGMP. Due to their diversity, which allows specific distribution at cellular and
      subcellular levels, PDEs can selectively regulate various cellular functions.
      Their critical role in intracellular signaling has recently designated them as
      new therapeutic targets for inflammation. The PDE superfamily represents 11 gene
      families (PDE1 to PDE11). Each family encompasses 1 to 4 distinct genes, to give
      more than 20 genes in mammals encoding the more than 50 different PDE proteins
      probably produced in mammalian cells. Although PDE1 to PDE6 were the first well
      characterized isoforms because of their predominance in various tissues and
      cells, their specific contribution to tissue function and their regulation in
      pathophysiology remain open research fields. This concerns particularly the newly
      discovered families, PDE7 to PDE11, for which roles are not yet established. In
      many pathologies, such as inflammation, neurodegeneration, and cancer,
      alterations in intracellular signaling related to PDE deregulation may explain
      the difficulties observed in the prevention and treatment of these pathologies.
      By inhibiting specifically the up-regulated PDE isozyme(s) with newly synthesized
      potent and isozyme-selective PDE inhibitors, it may be potentially possible to
      restore normal intracellular signaling selectively, providing therapy with
      reduced adverse effects.

PMID- 16102839
TI  - Pharmacological and clinical properties of calcimimetics: calcium receptor
      activators that afford an innovative approach to controlling hyperparathyroidism.
AB  - Circulating levels of calcium ion (Ca2+) are maintained within a narrow
      physiological range mainly by the action of parathyroid hormone (PTH) secreted
      from parathyroid gland (PTG) cells. PTG cells can sense small fluctuations in
      plasma Ca2+ levels by virtue of a cell surface Ca2+ receptor (CaR) that belongs
      to the superfamily of G protein-coupled receptors (GPCR). Compounds that activate
      the CaR and inhibit PTH secretion are termed 'calcimimetics' because they mimic
      or potentiate the effects of extracellular Ca2+ on PTG cell function. Preclinical
      studies with NPS R-568, a first generation calcimimetic compound that acts as a
      positive allosteric modulator of the CaR, have demonstrated that oral
      administration decreases serum levels of PTH and calcium, with a leftward shift
      in the set-point for calcium-regulated PTH secretion in normal rats. NPS R-568
      also suppresses the elevation of serum PTH levels and PTG hyperplasia and can
      improve bone mineral density (BMD) and strength in rats with chronic renal
      insufficiency (CRI). Clinical trials with cinacalcet hydrochloride (cinacalcet),
      a compound with an improved metabolic profile, have shown that long-term
      treatment continues to suppress the elevation of serum levels of calcium and PTH
      in patients with primary hyperparathyroidism (1HPT). Furthermore, clinical trials
      in patients with uncontrolled secondary hyperparathyroidism (2HPT) have
      demonstrated that cinacalcet not only lowers serum PTH levels, but also the serum
      phosphorus and calcium x phosphorus product; these are a hallmark of an increased
      risk of cardiovascular disease and mortality in dialysis patients with end-stage
      renal disease. Indeed, cinacalcet has already been approved for marketing in
      several countries. Calcimimetic compounds like cinacalcet have great potential as
      an innovative medical approach to manage 1HPT and 2HPT.

PMID- 16102840
TI  - Intracellular signaling pathways that regulate behavioral responses to ethanol.
AB  - Recent evidence indicates that ethanol modulates the function of specific
      intracellular signaling cascades, including those that contain cyclic adenosine
      3', 5'-monophosphate (cAMP)-dependent protein kinase A (PKA), protein kinase C
      (PKC), the tyrosine kinase Fyn, and phospholipase D (PLD). In some cases, the
      specific components of these cascades appear to mediate the effects of ethanol,
      whereas other components indirectly modify responses to ethanol. Studies
      utilizing selective inhibitors and genetically modified mice have identified
      specific isoforms of proteins involved in responses to ethanol. The effects of
      ethanol on neuronal signaling appear restricted to certain brain regions, partly
      due to the restricted distribution of these proteins. This likely contributes
      specificity to ethanol's actions on behavior. This review summarizes recent work
      on ethanol and intracellular signal transduction, emphasizing studies that have
      identified specific molecular events that underlie behavioral responses to
      ethanol.

PMID- 16102841
TI  - An autonomous implantable computer for neural recording and stimulation in
      unrestrained primates.
AB  - To perform neurobiological experiments on freely behaving primates, we have
      developed a miniature battery-powered implantable computer capable of recording
      and stimulating through chronic electrodes in the cortex. The device has: (1) an
      analog front end with a four-pole bandpass filter (500 Hz-5 kHz), programmable
      gain and offset nulling; (2) an analog-to-digital converter to sample the data at
      11.7 ksps; (3) a programmable microcontroller to discriminate spikes in real time
      and perform computations; (4) a stimulator to deliver biphasic current pulses of
      up to 100 muA with variable pulse width and frequency; (5) a 4 Mbit non-volatile
      memory to store biological data; (6) a 57.6 kbps infrared data link for wireless
      communications with a hand-held or desktop computer. The device is enclosed in a
      5.5 cm x 5 cm x 3 cm titanium casing on the monkey's head along with a 3.3 V
      lithium battery and an array of cortical electrodes. In in vivo tests, the device
      was able to record stable cell discharge continuously for time periods of a week
      or more. After downloading the parameters for recording, stimulation,
      discrimination, and other computations, the device is capable of operating
      autonomously, delivering stimuli to one electrode triggered by spikes recorded at
      a separate site.

PMID- 16102842
TI  - The influence of environment on development of the mucosal immune system.
AB  - The mucosal immune system expresses active responses against pathogens and also
      tolerance against harmless food and commensal bacterial antigens. The mechanisms
      that determine which of these outcomes occur after recognition of antigens by T
      cells are not clear. One possibility is that it is determined by the initial
      interaction between a dendritic and a naive T-cell in organised lymphoid tissue.
      However, such organised structures are, evolutionarily, quite recent and the
      original immune system must have made appropriate responses in more diffuse
      immunological architecture; a second possibility is that the critical interaction
      is between primed T-cells and their environment, in the lamina propria of the
      intestine. The mucosal immune system of neonates is poorly developed and
      inefficient at expressing appropriate immune responses. Development is influenced
      by a range of environmental factors including maternally derived antigen or
      antibody and commensal flora and pathogens. The intestine is a complex
      immunological structure in which the immune system and the macro- and
      microenvironment interact.

PMID- 16102843
TI  - Ability to differentiate between cp and ncp BVDV by microarrays: towards an
      application in clinical veterinary medicine?
AB  - Microarray expression profiling provides a comprehensive portrait of the
      transcriptional world enabling us to view the organism as a 'system' that is more
      than the sum of its parts. The vigilance of cells to environmental change, the
      alacrity of the transcriptional response, the short half-life of cellular mRNA
      and the genome-scale nature of the investigation collectively explain the power
      of this method. These same features pose the most significant experimental design
      and execution issues which, unless surmounted, predictably generate a distorted
      image of the transcriptome. Conversely, the expression profile of a properly
      conceived and conducted microarray experiment can be used for hypothesis testing:
      disclosure of the metabolic and biosynthetic pathways that underlie adaptation of
      the organism to infectious processes; the identification of co-ordinately
      regulated genes; the regulatory circuits and signal transduction systems that
      mediate the adaptive response; and temporal features of developmental programmes.
      The study of viral pathogenesis by microarray expression profiling poses special
      challenges and opportunities. Although the technical hurdles are many, obtaining
      expression profiles of an organism growing in tissue will probably reveal
      strategies for growth and survival of the virus in the host's cells. Here, we
      show data obtained using a tailored microarray system based on synthetic
      polynucleotides derived from human sequences (SIRS-Lab GmbH, Jena, Germany) to
      study the effect of cytopathogenic (cpe) and non-cytopathogenic (ncp) bovine
      viral diarrhoea virus (BVDV) infection of bovine macrophages, focusing on
      intracellular signalling molecules. Of the 575 genes present on the array, more
      than 70% showed a reaction with the oligonuleotides spotted on the array, and 26
      genes were differentially expressed comparing cDNA derived from cpe and ncp
      infected cells. These data will help to further understand our knowledge
      regarding BVDV infection, and will especially help to understand differences in
      cellular responses to cpe and ncp biotypes.

PMID- 16102844
TI  - Interleukin-8 mRNA expression in synovial fluid of canine stifle joints with
      osteoarthritis.
AB  - The objective of this study was to examine and compare the presence of
      interleukin (IL)-8 mRNA in canine stifle osteoarthritis (OA) differing in
      etiopathogenesis. Synovial fluid (SF) samples were collected from 24 clinically
      normal stifle joints and 46 diseased stifle joints (32 stifle joints with cranial
      cruciate ligament rupture (CCLR), 2 joints with CCLR and patella luxation (PL), 7
      joints with medial PL and 5 joints with primary OA). The samples were centrifuged
      to collect synovial fluid cells for RNA extraction. Reverse transcription
      polymerase chain reaction (RT-PCR) was performed to obtain cDNA from all samples.
      Canine IL-8 mRNA expression was determined using real time PCR. Synovial fluid
      glass smears were made of all samples and coloured with H&E for differential cell
      counts. All stifle joints were radiographed and graded for the severity of OA.
      Sixty-one percent (28/46) of the samples from canine stifle OA had IL-8 mRNA
      expression in contrast to 4% (1/24) in the control stifle joints. This difference
      in prevalence is highly significant. There were no statistically significant
      pairwise differences among the mean ranks of the various OA groups for the
      absolute amount of IL-8 mRNA expression. Neither was there a link between the
      severity of OA (determined by radiographic evaluation) and the presence of IL-8
      in the SF nor any significant difference in the absolute amount of IL-8 between
      the different OA grades. No statistical difference was found in differential cell
      counts between IL-8-positive and -negative SF samples. IL-8 cannot be used as a
      specific joint disease marker since IL-8 expression is found in OA differing in
      etiopathogenesis. It might, however, relate to the ongoing inflammation within
      the joint.

PMID- 16102845
TI  - Vertigo and balance problems in children--an epidemiologic study in Finland.
AB  - OBJECTIVES: There is only scant data about the frequency and characteristics of
      vertigo in children. The aim of the study was to determine the prevalence and
      characteristics of vertigo and balance problems in children aged between 1 and 15
      years. METHOD: One thousand and fifty children aged from 1 to 15 years from one
      child welfare unit and three schools in Helsinki University Hospital District
      received a questionnaire acquiring about their dizzy symptoms. RESULTS: Of 1050
      eligible children, 938 (89%) or a caregiver completed a simple screening
      questionnaire, 8% had experienced vertigo and 23% of these it was so severe
      vertigo that it prevented their present activity. Reason for vertigo was unknown
      in one third of the children and 69% could name a provocative factor for their
      vertigo. CONCLUSION: Balance problems are not rare in children and can limit
      their daily activities.

PMID- 16102846
TI  - Surgical management of cervical ganglioneuromas in children.
AB  - OBJECTIVE: To review the experience with ganglioneuromas in the head and neck of
      children including presentation, diagnostic testing, treatments, and outcomes.
      DESIGN: Case series. Retrospective chart review. SETTING: Tertiary care hospital.
      PATIENTS OR OTHER PARTICIPANTS: All patients with a history of ganglioneuroma of
      the neck in each authors practice were reviewed. All pathologically confirmed
      occurrences were eligible for inclusion, and five patients met these criteria.
      RESULTS: Five patients underwent surgical excision of head and neck
      ganglioneuromas between 1988 and 2004. There were no occurrences of secretory
      tumors, therefore all of the patients presented with enlarging masses. In all
      cases, the tumor arose from the cervical sympathetic chain, and thus, patients
      had subsequent ipsilateral Horner's Syndrome following resection. No synchronous
      tumors were noted, nor has a recurrent tumor been observed to this point.
      Complete excision was possible in all cases via a transcervical, or transoral
      approach, without mandibulotomy. CONCLUSIONS: Ganglioneuroma of the neck is a
      rare tumor that most commonly presents as an enlarging neck mass. Complete
      surgical excision is the treatment of choice, and in this series of children was
      possible with transcervical approach, and once via transoral approach. This tumor
      may be suspected in children who are otherwise asymptomatic, and present with
      long history of enlarging neck masses.

PMID- 16102847
TI  - Traumatic laryngotracheal stenosis--an alternative surgical technique.
AB  - Reconstruction of combined laryngotracheal stenosis requires complex techniques
      including resection and incorporation of grafts and stents that can be performed
      as single or multistaged procedure. A complicated case of traumatic
      laryngotracheal stenosis was managed by us, surgical technique is discussed. A 16
      year-old male presented with Stage-3 laryngotracheal stenosis of grade-3 to 4
      (>70% of the complete obstruction of tracheal lumen) of 5 cm segment of the
      larynx and trachea. Restoration of the critical functions of respiration and
      phonation was achieved in this patient by resection anastomosis of the trachea
      and with subglottic remodeling. Resection of 5 cm long segment of trachea and
      primary anastomosis in this case would have created tension at the site of
      anastomosis. So we did tracheal resection of 3 cm segment of trachea along with
      subglottic remodeling instead of removing the 5 cm segment of stenosed
      laryngotracheal region and doing thyrotracheal anastomosis. In complicated long
      segment, laryngotracheal stenosis, tracheal resection and subglottic remodeling
      with primary anastomosis can be an alternative approach. Fibrin glue can be used
      to support free bone/cartilage grafts in laryngotracheal reconstructions.

PMID- 16102848
TI  - Adherence to therapeutic guidelines for acute otitis media in children younger
      than 2 years.
AB  - OBJECTIVES: to analyze adherence to therapeutic guidelines for AOM. METHODS:
      Descriptive retrospective study of community primary care providers in southern
      Israel. Study population (n = 590) included all children aged 0-48 months
      diagnosed with AOM in PED during the year 2000 who had a referral letter from a
      community physician and an AOM diagnosis confirmed by tympanocentesis. AOM
      antibiotic treatment was considered appropriate when in accord with CDC and local
      therapeutic guidelines. RESULTS: Referral letter data allowing characterization
      of AOM by category were available in 471 (79.8%) children, 320 (68%) with simple
      AOM and 151(32%) with complicated AOM. AOM diagnosis made by the primary care
      physician was in accord with PED diagnosis in 365/590 (62%) patients. Three
      hundred and fifty-five (60.2%) patients did not receive antibiotics in the
      community. Of 365 (62%) children diagnosed with AOM in the community, 235 (64.4%)
      were treated with antibiotics prior to arrival to PED. Amoxicillin was prescribed
      to 109 (46.4%), cefuroxime axetil to 48 (20.4%), amoxicillin/clavulanate to 31
      (13.2%) and i.m. ceftriaxone to 20 (8.5%) of the patients. Eighty-three (25.9%)
      patients with simple AOM were treated with antibiotics in the community and only
      46 (55.4%) received amoxicillin according to the therapeutic guidelines. Eighty
      one (53.6%) patients with complicated AOM were treated with antibiotics in the
      community and only 41 (50.6%) of them received antibiotics according to AOM
      therapeutic guidelines. More antibiotics were prescribed in the community to
      patients with complicated AOM than to patients with simple AOM (81/151, 53.6%
      versus 83/320, 25.9%, respectively, p < 0.001). Adherence to therapeutic
      guidelines was similar between the simple and the complicated AOM groups (46/83,
      55.4% versus 41/81, 50.6%, respectively, p = 0.5). CONCLUSION: We found partial
      adherence to AOM therapeutic guidelines among primary care providers in the
      community in Southern Israel.

PMID- 16102849
TI  - A novel and rapid method to quantify cytolytic replication of picornaviruses in
      cell culture.
AB  - Determining viral titers is a key issue in a wide variety of studies regarding
      different aspects of virology. The standard methods used for determining
      picornavirus titers are endpoint titration assay and plaque assay, both time
      consuming and laborious. The method described uses the tetrazolium salt MTT (3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide) that is reduced to
      formazane by cellular dehydrogenase, genes shown to be down-regulated during
      picornavirus infection. The amount formazane produced correlates with the viral
      titers obtained and can easily be measured using an ELISA plate reader. The
      colorimetric method has been evaluated using virus types from different genera of
      the Picornaviridae family. The MTT method reduces the time spent on determining
      the viral titers and still maintains a reliable accuracy.

PMID- 16102850
TI  - Direct RT-PCR method for detecting two chrysanthemum viroids using minimal
      amounts of plant tissue.
AB  - A direct reverse transcription-polymerase chain reaction (RT-PCR) method for
      detecting the chrysanthemum stunt viroid (CSVd) and chrysanthemum chlorotic
      mottle viroid (CChMVd) to screen for a viroid-free chrysanthemum plant at a small
      plant size was established and named microtissue direct RT-PCR. A razor or
      syringe needle was used for RNA template preparations. Under a stereoscopic
      microscope, a razor or syringe needle was used to pierce, a tissue sample to a
      depth of 0.1-0.2mm, and the sample was directly transferred to the RT mixtures.
      Methods using razors or needles for the preparation of templates could detect
      CSVd and CChMVd with a high sensitivity. The most sensitive method used a razor
      or syringe needle to acquire template from the shoot tips. Using the microtissue
      direct RT-PCR method, both viroids could be detected from the high- and low
      viroid-concentration plants. The microtissue direct RT-PCR method was more
      sensitive than a conventional template preparation method. Using the microtissue
      direct RT-PCR method established in this study, the laborious subculture step
      could be omitted because detecting viroids and screening for viroid-free plants
      even at a small plant size before the subculture could be possible. In addition,
      the microtissue direct RT-PCR method could also be a powerful tool for clarifing
      the viroid distribution among microtissues, such as shoot apical meristems.

PMID- 16102851
TI  - Production of monoclonal antibodies against Rift Valley fever virus Application
      for rapid diagnosis tests (virus detection and ELISA) in human sera.
AB  - This paper describes the production and characterization of RVFV monoclonal
      antibodies. The characteristics of 32 out of 55 ELISA and/or IFA positive
      monoclonal antibodies were determined, including the RVFV components against
      which they are directed. One monoclonal antibody recognized the nucleoprotein, 15
      the Gc and 16 the Gn. Among the latter ones, five monoclonal antibodies possess
      another specificity and recognized both Gn and either the nucleoprotein (four of
      them) or the NSs protein (one). To validate the use of these monoclonal
      antibodies for diagnosis tests, a pool of monoclonal antibodies reacting with the
      structural proteins was prepared and used successfully to detect RVFV from cell
      culture as well as viral antigen-antibody complex in ELISA.

PMID- 16102852
TI  - Safe method for isolation of prion protein and diagnosis of Creutzfeldt-Jakob
      disease.
AB  - Creutzfeldt-Jakob disease (CJD) is a fatal progressive infectious encephalopathy
      of humans characterized by spongiform degeneration of the brain. Detection of
      protease-resistant low molecular weight proteins, referred to as 'prions', in the
      brain is essential for diagnosis. Protease-based methods for prion detection are
      problematic due to variable susceptibility of prion proteins to proteinase-K
      digestion. Since CJD brain samples are infectious at all stages of the prion
      extraction process, we set out to develop a laboratory safe method for prion
      purification. We lysed the tissues with guanidine thiocyanate followed by phenol
      extraction of the proteins. Western blotting using prion-specific MAB 3F4
      revealed primarily low molecular weight unglycosylated prion (UGP) bands in all
      CJD cases (19) while the predominant banding in all normal brains (14)
      represented glycosylated prion (GP). Density readings of the blots revealed the
      UGP/GP ratio to be significantly different in CJD versus normal brains, with an
      inverse UGP/GP ratio in CJD. Using this method, we discovered one previously
      undiagnosed CJD case when we screened 19 brains from the Louisiana State
      University Alzheimer disease brain bank. Our method is a safe and reliable way of
      detecting abnormal prion proteins (p<0.0001) and is adaptable to both diagnostic
      and research laboratories.

PMID- 16102853
TI  - Mice deficient in microtubule-associated protein MAP1B show a distinct behavioral
      phenotype and altered retina function.
AB  - We investigated mice deficient for the microtubule-associated protein MAP1B, a
      cytoskeletal element highly expressed in the developing nervous system, for
      altered performance in behavior, learning, and memory. Using the multiple T-maze,
      the open field and the Morris water maze we found that mice homozygous for a
      deletion of the MAP1B gene demonstrate impaired locomotor activity most likely
      correlated to a lack of physical endurance in general. In contrast, there were no
      significant differences in cognitive function and memory retention. In addition,
      we performed electroretinography and observed a reduction of the a-wave amplitude
      in response to single flash, white light stimulation. Taken together, these data
      provide further evidence for an important role of MAP1B in synaptic
      neurotransmission.

PMID- 16102854
TI  - Comparison of cytochemical procedures to estimate lysosomal biomarkers in mussel
      digestive cells.
AB  - Enlargement and membrane destabilisation in digestive cell lysosomes of mussels
      are biomarkers of pollution effect. Cytochemical methods are currently applied to
      determine lysosomal membrane stability (LMS) and lysosomal structural changes
      (LSC). LMS, determined after grading N-acetyl-beta-hexosaminidase activity on
      cryotome sections of digestive gland, is measured as labilisation period (LP).
      LSC, determined after image analysis of cryotome sections where beta
      glucuronidase activity is revealed, are measured as lysosomal volume (Vv),
      surface (Sv), numerical (Nv) densities and surface-to-volume ratio (S/V). Both
      methods have now been compared in a field study. Mussels were collected from
      Biscay Bay (Plentzia, reference; Muskiz, moderately polluted) and North Aegean
      Sea (Olympiada, reference; Limani, heavily polluted). Higher Vv and Sv and lower
      S/V and LP were recorded in polluted sites than in reference sites. Significant
      correlations with LP were found for Vv and S/V. The cost/effectiveness and
      environmental significance of both methods are discussed.

PMID- 16102855
TI  - Long-term infusion of nutrients (total parenteral nutrition) suppresses
      circulating ghrelin in food-deprived rats.
AB  - BACKGROUND: Ghrelin derives from endocrine cells (A-like cells) in the stomach
      (mainly the oxyntic mucosa). Its concentration in the circulation increases
      during fasting and decreases upon re-feeding. This has fostered the notion that
      the absence of food in the upper gastrointestinal (GI) tract stimulates the
      secretion of ghrelin. The purpose of the present study was to determine the
      concentration of ghrelin in serum and oxyntic mucosa after replacing food with
      intravenous (iv) infusion of nutrients for 8 days using the technique known as
      total parenteral nutrition (TPN) MATERIALS AND METHODS: Male Sprague-Dawley rats
      (200-250 g) were given nutrients (lipids, glucose, amino acids, minerals and
      vitamins) by iv infusion for 8 days during which time they were deprived of food
      and water; another group was deprived of food for 24-48 h (fasted controls),
      while fed controls had free access to food and water. Serum ghrelin, gastrin and
      pancreastatin concentrations were measured together with the ghrelin content of
      the oxyntic mucosa. Plasma insulin and glucose as well as serum lipid
      concentrations were also determined. RESULTS: Fasted rats had higher serum
      ghrelin than TPN rats and fed controls. The oxyntic mucosal ghrelin concentration
      (and content) was lower in TPN rats than in fasted rats or fed controls. The
      serum gastrin and pancreastatin concentrations were lower in TPN rats and fasted
      rats than in fed controls. The plasma insulin concentration was 87 pmol/l+/-8
      (SEM) in TPN rats compared to 101+/-16 pmol/l in fed controls; it was 26+/-14
      pmol/l in fasted rats. The basal plasma glucose level was 11+/-0.6 mmol/l in TPN
      rats and 12+/-0.8 mmol/l in fed controls; it was 7+/-0.3 mmol/l in fasted rats.
      In TPN rats, the serum concentrations of free fatty acids, triglycerides and
      cholesterol were increased by 100%, 50% and 25%, respectively, compared to fed
      controls. Fasted rats had higher circulating concentrations of free fatty acids
      (20%) and lower concentrations of triglycerides (-40%) than fed controls; fasted
      rats did not differ from fed controls with respect to serum cholesterol.
      CONCLUSION: The circulating ghrelin concentration is high in situations of
      nutritional deficiency (starvation) and low in situations of nutritional plenty
      (free access to food or TPN). The actual presence or absence of food in the GI
      tract seems irrelevant. Circulating insulin and glucose concentrations did not
      differ much between TPN rats and fed controls; serum lipids, however, were
      elevated in the TPN rats. We suggest that elevated blood lipid levels contribute
      to the suppression of circulating ghrelin in rats subjected to TPN for 8 days.

PMID- 16102856
TI  - Tissue-specific and glucose-responsive expression of the pancreatic derived
      factor (PANDER) promoter.
AB  - Pancreatic derived factor (PANDER) is a recently identified cytokine-like protein
      that is dominantly expressed in the islets of Langerhans of the pancreas. To
      investigate the mechanism of tissue-specific regulation of PANDER, we identified
      and characterized the promoter region. The transcriptional start site was
      identified 520 bp upstream of the translational start codon by 5'-RLM-RACE.
      Computer algorithms identified several islet-associated and glucose-responsive
      binding motifs that included A and E boxes, hepatocyte nuclear factors 1 and 4,
      Oct-1, and signal transducer and activator of transcription 3, and 5. Reporter
      gene analysis revealed cell type-specific PANDER promoter expression in islet and
      liver-derived cell lines. Levels of PANDER mRNA were directly concordant to the
      observed cell type-specific PANDER promoter gene expression. The minimal element
      was mapped to the 5'-UTR and located between +200 and +491 relative to the
      transcriptional start site and imparted maximal gene expression. In addition,
      several putative glucose-responsive binding sites were further functionally
      characterized to reveal critical regulatory elements of PANDER. The PANDER
      promoter was demonstrated to be glucose-responsive in a dose-dependent manner in
      murine insulinoma beta-TC3 cells and primary murine islets, but unresponsive in
      glucagon-secreting alpha-TC3 cells. Our findings revealed that the 5'-UTR of
      PANDER contains the minimal element for gene expression and imparts both tissue
      specificity and glucose-responsiveness. The regulation of PANDER gene expression
      mimics that of insulin and suggests a potential biological function of PANDER
      involved in metabolic homeostasis.

PMID- 16102857
TI  - Genomic medicine and thrombotic risk: who, when, how and why?
AB  - Major advances in Human Genome research could significantly change the clinical
      medical practice, providing new possibilities for both diagnosing and treating
      common pathologies. Many genetic tests are now commercially available for
      predicting future risk of common disorders. However, genetic testing has
      potential benefits but also limitations for the patients, and it should not be
      used to 'screen' the general population. Diagnostic assays for a predisposition
      of both venous and arterial thrombosis are among the most requested genetic tests
      in molecular diagnostics laboratories. However, there is considerable uncertainty
      as to how this information should be utilized in patient management. Both the
      medical community and the patients need to obtain accurate information concerning
      the appropriate use of genetic testing. The purpose of this article is to discuss
      the usefulness and the practical applications of thrombotic genetic testing in
      order to define which patients should be tested for both venous and arterial
      thrombotic risk as well as to have an acceptable cost/benefit ratio and to
      prevent patients' anxiety.

PMID- 16102858
TI  - Late complications following the deployment of drug eluting stents.
AB  - Recently, attention has been focused on late complications related to drug
      eluting stents (DES) [Farb A, Burke AP, Kolodgie FD, Virmani R. Pathological
      mechanisms of fatal late coronary stent thrombosis in humans. Circulation 108
      (2003) 1701-6; McFadden EP, Stabile E, Regar E, Cheneau E, Ong AT, Kinnaird T, et
      al. Late thrombosis in drug-eluting stents after discontinuation of platelet
      therapy. Lancet 364 (2004) 1519-21; Eisenberg MJ. Drug-eluting stents: some bare
      facts. Lancet 364 (2004) 1466-7, [1-3]. We present two cases with late stent
      thrombosis (LST) and one case with a stent-related aneurysm. All patients were
      treated with the paclitaxel coated stent (Taxus-R) which is the most commonly
      used DES in our department.

PMID- 16102859
TI  - Evaluation of a French ELISA for the detection of Salmonella Enteritidis and
      Salmonella Typhimurium in flocks of laying and breeding hens.
AB  - In France, the regular and compulsory detection of Salmonella Enteritidis (SE)
      and Salmonella Typhimurium (ST) in flocks of breeding and laying hens is based on
      bacteriological examination of environmental swabs and faeces samples. The aim of
      this study was to compare this bacteriological examination with a serological
      method (ELISA) developed in our laboratory. This ELISA was first evaluated by use
      of artificially infected hens. During these experimental infection studies,
      several groups of hens were inoculated with SE, ST, different vaccines and
      different Salmonella serovars to calculate the experimental parameters of our
      ELISA. Then, in a field study, 43 flocks were followed monthly using two
      bacteriological samples (environmental swab and pool of faeces) and 20
      serological samples (sera or yolks). Twenty-seven flocks without SE or ST gave a
      negative serological response throughout their surveillance. Among the 10 various
      serovars different from SE and ST isolated in this study, S. Heidelberg, S. Agona
      and S. Hadar gave seropositive results in seven flocks. Consequently, this ELISA
      was not specific of SE and ST as it detected serovars sharing or not common
      antigens with SE and ST. Seropositive results were also obtained each month for
      two flocks where no Salmonella could be isolated. Finally, in seven flocks found
      infected with SE or ST, the positive ELISA results appeared later than the
      bacteriological detection. Therefore, for the detection of chicken flocks
      recently infected with SE or ST, bacteriological examination currently used in
      France seems to be more appropriate than this ELISA.

PMID- 16102860
TI  - A new semi-nested PCR protocol to amplify large 18S rRNA gene fragments for PCR
      DGGE analysis of soil fungal communities.
AB  - The analysis of soil fungal communities by molecular fingerprinting and
      subsequent identification of the underlying populations require the amplification
      of a phylogenetically informative gene fragment. In this study we tested the
      reliability and suitability of the previously published fungal primer combination
      (NS1/FR1-GC) that amplifies almost the entire 18S rRNA gene for the DGGE analysis
      of fungal communities in soil samples from 36 sites. This direct PCR system
      failed to amplify the fragment of interest from the total DNA extracted from most
      of the soils tested. Thus, we developed a new semi-nested PCR system based on the
      initial amplification of over 1,700 bp of the 18S rRNA gene with a new primer
      combination, followed by a subsequent amplification with NS1/FR1-GC. By means of
      the PCR approach developed in this study distinct 18S rRNA gene amplicons could
      be reproducibly generated for all soil samples. Amplification tests with 101 soil
      fungal isolates showed that with the new semi-nested system 18S rRNA gene
      fragments could be obtained from more fungi than with the direct approach. The
      subsequent DGGE separation of community amplicons resulted in a high resolution
      and revealed reproducible complex soil fungal communities specific for each site,
      despite a minor variability between replicates of the same sample. The semi
      nested PCR system developed in this study, coupled with DGGE fingerprinting,
      offers a robust, reliable and sensitive tool for the analysis of soil fungal
      community structure.

PMID- 16102861
TI  - P300-based Stroop study with low probability and target Stroop oddballs: the
      evidence still favors the response selection hypothesis.
AB  - This paper addresses the issue of the locus of action in cognitive processing
      during Stroop effects. It uses the P300 latency to assess stimulus processing
      effects, but, for the first time, under conditions in which Stroop stimuli are
      rare and target stimuli. The study was also concerned with demonstrating that
      apparent P300s during verbal responding are in fact uninterpretable due to
      contamination of EEG by speech-related artifact. Three studies were presented. In
      Study 1, there were 3 blocks, each containing 1 of 3 types of rare Stroop stimuli
      (p = .15), congruent, neutral, and incongruent. There were also 3 response modes:
      button press (BUTTON), speaking aloud (VERBAL), and speaking to self (SILENT).
      Three sessions were used, each for a different response style. The only task was
      to name the color on each trial. In the 2 non-verbal blocks, Reaction Time (RT)
      varied by stimulus type; congruent < neutral < incongruent. P300 latency was the
      same across blocks in these non-verbal conditions in which one saw the classic Pz
      > Cz > Fz distribution. The much larger, speech artifact-contaminated "P300s" in
      the VERBAL blocks did suggest a Stroop effect, especially at Fz and Cz, where
      "P300s" were larger than at Pz. In Study 2, there were 2 response modes, VERBAL
      and SILENT, and only two rare Stroop stimuli; neutral and incongruent, 1 per
      block. In each of these blocks, one word-color combination was a designated
      target requiring a unique response. The subject was to name the color followed by
      a yes or no to categorize the target or non-target. Again the RT for incongruents
      was greater than RT for neutrals, without a parallel effect in P300 latency.
      Again, the rostral ERPs appeared artifactual in the VERBAL condition. Study 3 was
      a replication of the second study, except that motivated subjects, versus
      Psychology pool recruits, were used. The latency-RT correlation still failed to
      obtain. Thus, using classic P300-eliciting antecedents-rare and target (Stroop)
      stimuli-this study supports the view that the locus of Stroop interference is in
      response processing.

PMID- 16102862
TI  - Neuroprotective mechanisms of lidocaine against in vitro ischemic insult of the
      rat hippocampal CA1 pyramidal neurons.
AB  - To compare neuroprotective effects of lidocaine and procaine against ischemic
      insult, intracellular recordings were made from rat hippocampal CA1 pyramidal
      neurons in slice preparations. Superfusion of the slices with oxygen- and glucose
      deprived medium (in vitro ischemia) produced a rapid depolarization 6 min from
      the onset. When oxygen and glucose were reintroduced, the membrane depolarized
      further until it reached 0 mV, and thereafter the membrane showed no functional
      recovery. Pretreatment with lidocaine (10 microM), but not procaine (50 microM),
      restored the membrane potential after the reintroduction of oxygen and glucose.
      Lidocaine, compared to procaine, significantly inhibited the reduction in both
      tissue ATP content and flavoprotein fluorescence during and after in vitro
      ischemia. Under electron microscopy, only lidocaine well preserved the structure
      of mitochondria in the CA1 pyramidal cell body. Extracellular recordings revealed
      that procaine reduced the field postsynaptic potential whereas lidocaine
      augmented it. Both drugs reduced the presynaptic volley dose-dependently. Neither
      lidocaine nor procaine significantly affected a rapid rise of the intracellular
      Ca2+ level produced by in vitro ischemia in the CA1 region. All the results
      suggest that the neuroprotective lidocaine action is due to the protection of the
      mitochondria to maintain the tissue ATP content during and after in vitro
      ischemia.

PMID- 16102863
TI  - Is the brain influenced by a phone call? An EEG study of resting wakefulness.
AB  - We recorded the resting electroencephalogram of 20 healthy subjects in order to
      investigate the effect of electromagnetic field (EMF) exposure on EEG waking
      activity and its temporal development. The subjects were randomly assigned to two
      groups and exposed, in double-blind conditions, to a typical mobile phone signal
      (902.40 MHz, modulated at 217 Hz, with an average power of 0.25 W) before or
      during the EEG recording session. The results show that, under real exposure as
      compared to baseline and sham conditions, EEG spectral power was influenced in
      some bins of the alpha band. This effect was greater when the EMF was on during
      the EEG recording session than before it. The present data lend further support
      to the idea that pulsed high-frequency electromagnetic fields can affect normal
      brain functioning, also if no conclusions can be drawn about the possible health
      effects.

PMID- 16102864
TI  - Characterization of a 3944 Da bacteriocin, produced by Enterococcus mundtii ST15,
      with activity against Gram-positive and Gram-negative bacteria.
AB  - Strain ST15, isolated from soy beans, and identified as Enterococcus mundtii,
      produces a 3944 Da bacteriocin that inhibits the growth of Lactobacillus sakei,
      Enterococcus faecalis, Bacillus cereus, Propionibacterium sp., Clostridium
      tyrobutyricum, Acinetobacter baumanii, Klebsiella pneumoniae, Pseudomonas
      aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus
      caprinus. Bacteriocin ST15 is inactivated by proteinase K, pronase, pepsin,
      protease and Triton X-114, but not when treated with catalase, alpha-amylase,
      Triton X-100, SDS, Tween 20, Tween 80, urea and EDTA. No change in activity was
      recorded after 2 h at pH values between 2.0 and 12.0, and after treatment at 100
      degrees C for 90 min. Activity was, however, lost after treatment at 121 degrees
      C for 20 min. The mode of activity is bactericidal. The highest level of activity
      (51200 AU ml(-1)) was recorded when cells were grown in MRS broth, pH 6.5.
      Bacteriocin ST15 differs from other broad-spectrum bacteriocins described for
      Enterococcus spp. by being active against Gram-negative bacteria and by being
      smaller.

PMID- 16102865
TI  - Vacuolar H(+)-ATPase and plasma membrane H(+)-ATPase contribute to the tolerance
      against high-pressure carbon dioxide treatment in Saccharomyces cerevisiae.
AB  - As a non-thermal sterilization process, high-pressure carbon dioxide treatment
      (HPCT) is considered to be promising. The main sterilizing effect of HPCT is
      thought to be acidification in cytoplasm of microorganisms. We investigated the
      tolerance mechanism of Saccharomyces cerevisiae to HPCT with special reference to
      vacuolar and plasma membrane H(+)-ATPases. HPCT was imposed at 35 degrees C, 4 to
      10 MPa, for 10 min. slp1 mutant defective in vacuole morphogenesis was more
      sensitive to HPCT than its isogenic parent. Concanamycin A, a specific inhibitor
      of vacuolar H(+)-ATPase (V-ATPase), at 10 microM rendered the parent more HPCT
      sensitive to the level of slp1. To confirm further the contribution of V-ATPase
      to the tolerance against HPCT in S. cerevisiae, we compared vma1 mutant of V
      ATPase with its isogenic parent for their HPCT sensitivity. vma1 mutant was more
      sensitive to HPCT than its parent. Addition of 10 microM vanadate, an inhibitor
      of plasma membrane H(+)-ATPase (P-ATPase), to the wild type strains also
      increased the inactivation ratio. These results clearly show that V- and P
      ATPases contribute to the tolerance against HPCT in S. cerevisiae by accumulating
      excess H(+) from cytoplasm to vacuole and excluding H(+) outside of the cell,
      respectively.

PMID- 16102866
TI  - Stereoselective lipases from Burkholderia sp., cloning and their application to
      preparation of methyl (R)-N-(2,6-dimethylphenyl)alaninate, a key intermediate for
      (R)-Metalaxyl.
AB  - Two microbial strains (referred to as MC 16-3 and 99-2-1) that produce
      extracellular lipases were isolated from soil samples and identified as
      Burkholderia species. The lipases were partially purified by isopropyl alcohol
      precipitation and gave molecular weight of 33kDa. The lipases were characterized
      in terms of stereoselectivity with racemic methoxyethyl (R,S)-N-(2,6
      dimethylphenyl)alaninate and the genes encoding the proteins have been identified
      by homology alignment of lipases reported belonging to I.2 subfamily and their
      complete DNA sequences were determined. The lipases will be useful for the
      preparation of methyl (R)-N-(2,6-dimethylphenyl)alaninate, a key intermediate for
      the synthesis of (R)-Metalaxyl, which is one of the best-selling fungicides.

PMID- 16102867
TI  - Synthesis, characterization and immunogenicity of silk fibroin-L-asparaginase
      bioconjugates.
AB  - L-asparaginase (ASNase) is one basic drug in the treatment of acute lymphoblastic
      leukemia (ALL). Because its half-life time is too short and it is easy to arouse
      allergic reaction, use in practical clinic is considerably limited. Silk fibroin
      (SF) with different molecular mass from 40 to 120 kDa is a natural biocompatible
      protein and could be used as a novel bioconjugate for enzyme modification to
      overcome its usual shortcomings mentioned above. When the enzyme was
      bioconjugated covalently with the water-soluble fibroin by glutaraldehyde, the
      enzyme kinetic properties and immune characteristics in vivo of the resulting
      silk fibroin-L-asparaginase (SF-ASNase) bioconjugates were investigated in
      detail. The results show that the modified ASNase was characterized by its higher
      residual activity (nearly 80%), increased heat and storage stability and
      resistance to trypsin digestion, and its longer half-life (63 h) than that of
      intact ASNase (33 h). The abilities of intact and modified ASNases to arouse
      allergic reaction are 2(4) and 2(1) antibody titers, respectively. Bioconjugation
      of silk fibroin significantly helps to reduce the immunogenicity and antigenicity
      of the enzyme. The apparent Michaelis constants of the modified ASNase
      (K(m(app))=0.844 x 10(-3)mol L(-1)) was approximately six times lower than that
      of enzyme alone, which suggests that the affinity of the enzyme to substrate l
      asparagine elevated when bioconjugated covalently with silk fibroin. SF-ASNase
      bioconjugates could overcome the common shortcomings of the native form.
      Therefore, the modified ASNase coupled with silk fibroin has the potential values
      of being studied and developed as a new bioconjugate drug.

PMID- 16102868
TI  - Binary AdEasy vector systems designed for Tet-ON or Tet-OFF regulated control of
      transgene expression.
AB  - Here, we describe the construction of a set of binary adenovirus vectors encoding
      for a tetracycline-regulatable expression cassette and the Tet-ON or the Tet-OFF
      transcriptional activator proteins from a single viral chromosome. The rabies
      virus glycoprotein was cloned into the E1 region and the tetracycline activator
      proteins were inserted in both orientation in place of the E3 region. To further
      restrict background transcription, we also introduced a Lac repressor protein
      based roadblock to transcription elongation. To make the system more versatile it
      has been engineered into the commonly used AdEasy system. We show that rabies
      virus glycoprotein expression is tightly regulated with an essentially
      undetectable basal expression and a several 100-fold induced expression. In our
      vector backbone, the Tet-ON and the Tet-OFF systems appears to work with
      essentially the same efficiency. Thus, the choice of principle can be based on
      whether a positive or negative regulation of reporter gene activity is desirable.
      Taken together our results suggest that the binary vectors described here should
      be a valuable addition to the repertoire of viral vectors used in basic and
      medical research.

PMID- 16102869
TI  - The polypyrimidine tract-binding protein (PTB) is required for efficient
      replication of hepatitis C virus (HCV) RNA.
AB  - Our earlier work found that the polypyrimidine tract-binding protein (PTB)
      specifically interacts with the poly(U/C) tract of the hepatitis C virus (HCV) 3'
      untranslated region (3'UTR) [Luo, G., 1999. Cellular proteins bind to the poly(U)
      tract of the 3' untranslated region of hepatitis C virus RNA genome. Virology
      256, 105-118]. We report here that the phosphorylated form of PTB is associated
      with the membrane-bound HCV replication complex. To determine whether the PTB is
      required for HCV RNA replication, synthetic small interfering RNAs (siRNAs) were
      used to specifically knockdown PTB expression in the HCV replicon-harboring Huh7
      cells. The level of PTB expression was efficiently reduced by PTB-specific
      siRNAs. Consequently, the levels of HCV proteins as well as HCV RNA were
      proportionally decreased by increasing concentrations of PTB siRNA. However, the
      translation mediated by the encephamyocarditis virus internal ribosome entry site
      was unaffected, suggesting that the inhibition of HCV RNA replication by PTB
      siRNA was not due to its effect on the EMCV IRES-mediated translation.
      Collectively, these findings demonstrate that PTB is required for efficient HCV
      RNA replication in the cell.

PMID- 16102870
TI  - The hepatitis C virus NS3/4A protease complex interferes with pathways of the
      innate immune response.

PMID- 16102871
TI  - Injection of innocuous oils to create reactive barriers for bioremediation:
      laboratory studies.
AB  - In situ groundwater remediation may be achieved using stationary permeable
      barriers created by the injection of a substrate, such as innocuous vegetable
      oil, into the contaminated aquifer. The oil provides the electron donor
      stimulating microorganisms to degrade or sequester many contaminants. At present,
      little is known about the best procedures to use when injecting oil into an
      aquifer. In this investigation, laboratory column and sand tank studies were used
      as model systems to explore the effect of different injection parameters on the
      distribution of oil emulsions into water-saturated sand. The parameters
      investigated included injection pressures of 70, 1400 and 18,000 KPa; injection
      times of 15, 30, 60 or 120 s; and the influence of an emulsifier,
      polyoxyethylenesorbitan monooleate (Tween 80), upon the distribution of the
      injected oil. The longest injection patterns were achieved at 18,000 KPa. A
      pattern that was 46+/-1.8 cm long was produced with an 18,000 KPa injection for
      60 s. Increasing the injection time to 120 s increased the length of the pattern
      by only 6.5%. Tween 80 at concentrations of 0.05% increased the width of the
      injection patterns but did not increase the length of the pattern. A multi-ported
      injection probe might be used to create in situ permeable barriers approximately
      1 m wide.

PMID- 16102872
TI  - Dynamic factor analysis of groundwater quality trends in an agricultural area
      adjacent to Everglades National Park.
AB  - The extensive eastern boundary of Everglades National Park (ENP) in south Florida
      (USA) is subject to one of the most expensive and ambitious environmental
      restoration projects in history. Understanding and predicting the water quality
      interactions between the shallow aquifer and surface water is a key component in
      meeting current environmental regulations and fine-tuning ENP wetland restoration
      while still maintaining flood protection for the adjacent developed areas.
      Dynamic factor analysis (DFA), a recent technique for the study of multivariate
      non-stationary time-series, was applied to study fluctuations in groundwater
      quality in the area. More than two years of hydrological and water quality time
      series (rainfall; water table depth; and soil, ground and surface water
      concentrations of N-NO3-, N-NH4+, P-PO4(3-), Total P, F-and Cl-) from a small
      agricultural watershed adjacent to the ENP were selected for the study. The
      unexplained variability required for determining the concentration of each
      chemical in the 16 wells was greatly reduced by including in the analysis some of
      the observed time series as explanatory variables (rainfall, water table depth,
      and soil and canal water chemical concentration). DFA results showed that
      groundwater concentration of three of the agrochemical species studied (N-NO3-, P
      PO4(3-)and Total P) were affected by the same explanatory variables (water table
      depth, enriched topsoil, and occurrence of a leaching rainfall event, in order of
      decreasing relative importance). This indicates that leaching by rainfall is the
      main mechanism explaining concentration peaks in groundwater. In the case of N
      NH4+, in addition to leaching, groundwater concentration is governed by lateral
      exchange with canals. F-and Cl- are mainly affected by periods of dilution by
      rainfall recharge, and by exchange with the canals. The unstructured nature of
      the common trends found suggests that these are related to the complex spatially
      and temporally varying land use patterns in the watershed. The results indicate
      that peak concentrations of agrochemicals in groundwater could be reduced by
      improving fertilization practices (by splitting and modifying timing of
      applications) and by operating the regional canal system to maintain the water
      table low, especially during the rainy periods.

PMID- 16102873
TI  - Transport of hydrocarbons from an emplaced fuel source experiment in the vadose
      zone at Airbase Vaerlose, Denmark.
AB  - An emplaced hydrocarbon source field experiment was conducted in the relatively
      homogeneous sandy geology of the vadose zone at Airbase Vaerlose, Denmark. The
      source (10.2 l of NAPL) consisted of 13 hydrocarbons (n-, iso- and cyclo-alkanes
      and aromates) and CFC-113 as a tracer. Monitoring in the 107 soil gas probes
      placed out to 20 m from the centre of the source showed spreading of all the
      compounds in the pore air and all compounds were measured in the pore air within
      a few hours after source emplacement. Seven of the fourteen compounds were
      depleted from the source within the 1 year of monitoring. The organic vapours in
      the pore air migrated radially from the source. The CFC-113 concentrations seemed
      to be higher in the deeper soil gas probes compared with the hydrocarbons,
      indicating a high loss of CFC-113 to the atmosphere and the lack of degradation
      of CFC-113. For the first days after source emplacement, the transport of CFC
      113, hexane and toluene was successfully simulated using a radial gas-phase
      diffusion model for the unsaturated zone. Groundwater pollution caused by the
      vadose zone hydrocarbon vapours was only detected in the upper 30 cm of the
      underlying groundwater and only during the first 3 months of the experiment. Only
      the most water-soluble compounds were detected in the groundwater and
      concentrations decreased sharply with depth (approximately one order of magnitude
      within 10 cm depth) to non-detect at 30 cm depth. The groundwater table varied
      more than 1 m within the measurement period. However that did not influence the
      direction of the groundwater flow. Approximately 7 months after source
      emplacement the groundwater table rose more than 1 m within 1 month. That did not
      cause additional pollution of the groundwater.

PMID- 16102874
TI  - Age and physical activity influences on action monitoring during task switching.
AB  - Behavioral and neuroelectric indices of action monitoring were compared for 53
      high and low physically active older (60-71 years) and younger (18-21 years)
      adults during a task-switching paradigm in which they performed a task repeatedly
      or switched between two different tasks. The error-related negativity (ERN) of a
      response-locked event-related brain potential (ERP) and behavioral measures of
      response speed and accuracy were measured during the heterogeneous condition
      (switching randomly between two tasks) of the switch task. Results indicated that
      older adults exhibited a greater relative slowing in RT during heterogeneous
      blocks and smaller ERN amplitude compared to younger adults. Additionally,
      physical activity differences revealed a relatively smaller global switch cost
      for physically active older adults and decreased ERN amplitude, as well as
      increased post-error response slowing for older and younger physically active
      participants, compared to their less physically active counterparts. The findings
      suggest that both age and physical activity participation influence behavioral
      and neuroelectric indices of action monitoring and provide further evidence for
      the beneficial effects of physical activity on executive control.

PMID- 16102875
TI  - Construction and evaluation of a O139 Vibrio cholerae vaccine candidate based on
      a hemA gene mutation.
AB  - In this paper, we describe the development of VCUSM2, a live metabolic auxotroph
      of Vibrio cholerae O139. Auxotrophy was achieved by mutating a house keeping
      gene, hemA, that encodes for glutamyl-tRNA reductase, an important enzyme in the
      C5 pathway for delta-aminolevulenic acid (ALA) biosynthesis, which renders this
      strain dependent on exogenous ALA for survival. Experiments using the infant
      mouse and adult rabbit models show that VCUSM2 is a good colonizer of the small
      intestine and elicits greater than a four-fold rise in vibriocidal antibodies in
      vaccinated rabbits. Rabbits vaccinated with VCUSM2 were fully protected against
      subsequent challenge with 1 x 10(11) CFU of the virulent wild type (WT) strain.
      Experiments using ligated ileal loops of rabbits show that VCUSM2 is 2.5-fold
      less toxic at the dose of 1 x 10(6) CFU compared to the WT strain. Shedding of
      VCUSM2 in rabbits were found to occur for no longer than 4 days and its maximum
      survival rate in environmental waters is 8 days compared to the greater than 20
      days for the WT strain. VCUSM2 is thus a potential vaccine candidate against
      infection by V. cholerae O139.

PMID- 16102876
TI  - Deposition of contaminant aerosol on human skin.
AB  - Over recent years, it has been established that deposition of various types of
      pollutant aerosols (e.g., radioactive) on human skin can have serious deleterious
      effects on health. However, only few investigations in the past have been devoted
      to measurement of deposition velocities on skin of particles of the potentially
      problematic sizes. An experimental programme has shown the deposition velocities
      on skin of particles in the ca. 0.5-5 microm AMAD range to be high and generally
      associated with great variations. A series of investigations have been made to
      identify some of the factors that lead to this variation. Part of the variation
      was found to be caused by differences between individuals, whereas another part
      was found to be related to environmental factors. The identification of major
      influences on skin contaminant deposition is important in estimating health
      effects as well as in identifying means for their reduction.

PMID- 16102877
TI  - Evaluation of 137Cs fallout from the Chernobyl accident in a forest soil and its
      impact on Alpine Lake sediments, Mercantour Massif, S.E. France.
AB  - The Boreon area in the Mercantour Massif, S.E. France, was contaminated by
      radionuclides after the Chernobyl accident in the first days of May 1986.
      Sediments from a small mountain lake in this area were collected, as well as
      forest soils in its vicinity, in order to obtain 137Cs and 210Pb profiles.
      Calculated from the 210Pb inventory in a soil of a horizontal area, the flux is
      high in the area (0.06 Bqcm(-2)y(-1)) probably because of the great frequency of
      rain and uranium ores outcropping in the massif. The comparison of the 137Cs soil
      inventories and the unsupported 210Pb suggests that the 137Cs fallout due to the
      Chernobyl accident in the study site (Boreon) was at least 3.5 Bqcm(-2), more
      probably the double. The recent lake sediments still undergo a rather strong
      contamination by 137Cs and the sediment profiles show that the residence time of
      137Cs in the catchment area is long. The study area is frequented by many
      inhabitants of the city of Nice and other cities at the Mediterranean coast
      during week-end and during summer and winter holidays. Thus the 137Cs external
      exposure impact was evaluated at 2 mSvy(-1) for 2002 in the most contaminated
      point.

PMID- 16102878
TI  - Radioactivity in trinitite six decades later.
AB  - The first nuclear explosion test, named the Trinity test, was conducted on July
      16, 1945 near Alamogordo, New Mexico. In the tremendous heat of the explosion,
      the radioactive debris fused with the local soil into a glassy material named
      Trinitite. Selected Trinitite samples from ground zero (GZ) of the test site were
      investigated in detail for radioactivity. The techniques used included alpha
      spectrometry, high-efficiency gamma-ray spectrometry, and low-background beta
      counting, following the radiochemistry for selected radionuclides. Specific
      activities were determined for fission products (90Sr, 137Cs), activation
      products (60Co, 133Ba, 152Eu, 154Eu, 238Pu, 241Pu), and the remnants of the
      nuclear fuel (239Pu, 240Pu). Additionally, specific activities of three natural
      radionuclides (40K, 232Th, 238U) and their progeny were measured. The determined
      specific activities of radionuclides and their relationships are interpreted in
      the context of the fission process, chemical behavior of the elements, as well as
      the nuclear explosion phenomenology.

PMID- 16102879
TI  - Vertebral fractures and separations of endplates after traumatic loading of
      adolescent porcine spines with experimentally-induced disc degeneration.
AB  - BACKGROUND: Abnormalities of the intervertebral discs have been found in a high
      frequency among young elite athletes. Several studies have also reported that the
      adolescent spine, especially the vertebral growth zones, is vulnerable to trauma.
      However, there is incomplete knowledge regarding the injury mechanism of the
      growing spine. In this study, the injury patterns of the adolescent porcine spine
      with disc degeneration were examined. METHODS: Twenty-four male pigs were used. A
      degenerative disc was created by drilling a hole through the cranial endplate of
      a lumbar vertebra into the disc. Two months later the animals were sacrificed and
      the degenerative functional spinal units (segments) were harvested. The segments
      were divided into three groups and exposed to axial compression, flexion
      compression or extension compression to failure. The load and angle at failure
      were measured for each group. The segments were examined with magnetic resonance
      imaging and plain radiography before and after the loading and finally examined
      macroscopically and histologically. FINDINGS: The degenerated segments required
      considerably more compressive load to failure than non-degenerated segments.
      Creating a flexion injury required significantly more load than an extension
      injury. Fractures and/or separations of the endplates from the vertebral bodies
      were seen at the margins of the endplates and in the growth zone. Only severe
      separations and fractures could be seen on plain radiography and magnetic
      resonance imaging. INTERPRETATION: The weakest part of the adolescent porcine
      lumbar spine with experimentally-induced degeneration, when loaded in axial
      compression, flexion compression or extension compression, was the growth zone,
      and, to a lesser extent, the endplate. Degenerated discs seem to withstand higher
      mechanical loads than non-degenerated discs, probably due to altered stress
      distribution.

PMID- 16102880
TI  - An interdisciplinary physical-chemical approach for characterization of arsenic
      in a calciner residue dump in Cornwall (UK).
AB  - During the later stages of hard-rock mining in Cornwall, UK, widespread
      processing and refining of arsenic in purpose-built calciners resulted in severe,
      localized contamination of soils with arsenic. Several physical-chemical
      techniques were applied to characterize arsenic in a calciner residue dump: X-ray
      powder diffraction (XRD), sequential extraction combined with hyphenated
      speciation methods, and X-ray absorption spectroscopic (XAS) methods such as
      XANES (X-ray absorption near-edge structure) and EXAFS (extended X-ray absorption
      fine structure). Arsenic was predominantly present in pentavalent form, bound to
      amorphous or poorly-crystalline hydrous oxides of Fe (probably alpha-hematite). A
      small amount of a non-classified crystalline iron arsenate phase was found, viz.
      Fe2(As(AsO4)3). There was also evidence for the presence of some arsenate bound
      to quartz (alpha-SiO2). The overall results make us believe that the normally
      assumed relative safety, from a mobility point of view, is questionable since
      only a small fraction of arsenic is found in a crystalline iron arsenate form.

PMID- 16102881
TI  - Sociodemographic and attitudinal correlates of cervical screening uptake in a
      national sample of women in Britain.
AB  - Sociodemographic and attitudinal correlates of self-reported cervical screening
      uptake were investigated among 1307 women in the target age group who
      participated in two national surveys conducted in Britain in 1999. Evidence for
      inequalities in screening uptake was mixed. Of the socioeconomic indicators, only
      age of completed full-time education showed a significant effect in the
      multivariate analysis. The strong effects of car ownership and housing tenure in
      the univariate analyses were eliminated by controlling for marital status, which
      showed a robust association with uptake. Uptake was highest among married and
      separated women and lowest among single and widowed women. There was no evidence
      that the effects of marital status and education were mediated by the attitudinal
      variables. Anticipated embarrassment and attitudes to screening (e.g., "There's
      no point going for screening if you don't have any symptoms") were significant
      independent predictors of uptake. These findings suggest that information
      campaigns need to address feelings of embarrassment and lack of understanding of
      the rationale for screening and that efforts should be made to encourage single
      and widowed women to attend.

PMID- 16102882
TI  - Homocysteine and brain atrophy.
AB  - Homocysteine (Hcy) has been implicated as a risk factor for vascular disease as
      well as brain atrophy. There is evidence to implicate Hcy in increased oxidative
      stress, DNA damage, the triggering of apoptosis and excitotoxicity, all important
      mechanisms in neurodegeneration. Hcy is also prothrombotic and proatherogenic,
      and causes damage to the vessel wall. It is related to brain atrophy in older
      individuals, and possibly to white matter hyperintensities (WMH) in the brain.
      Epidemiological evidence and longitudinal data support Hcy as a risk factor for
      cognitive impairment and Alzheimer's Disease (AD). This may be due to
      cerebrovascular as well as direct neurotoxic mechanisms. Its role in Parkinson
      Disease (PD) is less well supported. High Hcy has been suggested as a mediating
      factor in alcohol-related brain atrophy. The high prevalence of
      hyperhomocysteinemia in the population and its easy treatability make Hcy an
      interesting amino acid for future intervention studies in the prevention of
      degenerative brain disorders. Intervention studies are necessary to confirm its
      aetiological role.

PMID- 16102883
TI  - Synergistic fungicidal activity of Cu(2+) and allicin, an allyl sulfur compound
      from garlic, and its relation to the role of alkyl hydroperoxide reductase 1 as a
      cell surface defense in Saccharomyces cerevisiae.
AB  - Cu(2+) showed a dose-dependent fungicidal activity against Saccharomyces
      cerevisiae cells, and its lethal effect was extremely enhanced in the presence of
      allicin, an allyl sulfur compound from garlic. The fungicidal activity of Cu(2+)
      was unaffected or rather attenuated by other sulfur-containing compounds such as
      N-acetyl-cysteine, l-cysteine or dithiothreitol. Ca(2+) could absolutely protect
      against the lethal effect of Cu(2+) itself, but showed no protection against the
      fungicidal activity of Cu(2+) newly generated in combination with allicin. Cu(2+)
      accelerated an endogenous generation of reactive oxygen species (ROS) in S.
      cerevisiae cells at a lethal concentration, but such intracellular oxidative
      stress induction was not observed during cell death progression upon treatment
      with Cu(2+) and allicin. A surfactant, sodium N-lauroyl sarcosinate (SLS),
      enhanced the solubilization of a few proteins including alkyl hydroperoxide
      reductase 1 (AHP1) in intact cells, accounting for the absence of this protein in
      the extract from allicin-treated cells. Allicin-treated cells were rendered
      extremely sensitive to the subsequent Cu(2+) treatment as in the case of SLS
      treated cells. Allicin-treated cells and SLS-treated cells similarly showed an
      increased sensitivity to exogenously added tert-butyl hydroperoxide (t-BOOH), an
      organic peroxide that is detoxified by the action of AHP1. Our study suggests
      that allicin influences the mode of cell surface localization or the related
      function of AHP1 as a defense against phospholipid peroxidation by the external
      action of Cu(2+).

PMID- 16102884
TI  - Effect of organophosphorus insecticides and their metabolites on astroglial cell
      proliferation.
AB  - Though little attention has been given to the possibility that glial cells may
      represent a target for the developmental neurotoxicity of organophosphorus (OP)
      insecticides, recent evidence, obtained in particular with chlorpyrifos (CP),
      suggests that developmental exposure to this compound may indeed target
      astrocytes. To substantiate and expand these observations, we carried out a
      series of in vitro studies utilizing fetal rat astrocytes and a human astrocytoma
      cell line, 1321N1 cells, to investigate the effect of the OPs CP, diazinon (DZ)
      and parathion (P), their oxygen analogs chlorpyrifos oxon (CPO), diazoxon (DZO)
      and paraoxon (PO), and their metabolites 3,5,6-trichloro-2-pyridinol (TCP), 2
      isopropyl-6-methyl-4-pyrimidol (IMP) and para-nitrophenol (PNP), on cell
      proliferation. In fetal rat astrocytes and astrocytoma cells maintained in serum,
      CP, DZ, P, CPO, DZO, and PO induced a concentration-dependent inhibition in
      [(3)H]thymidine incorporation with a very similar potency (IC(50) between 45 and
      57 microM). Among the other metabolites, PNP was the most potent (IC(50)=70-80
      microM), while TCP and IMP were much less effective (IC(50)>100 microM).
      Cytotoxicity appears to account only for a small part of the effect on DNA
      synthesis. OP insecticides and their oxons were three- to six-fold more potent in
      inhibiting [(3)H]thymidine incorporation when cells were synchronized in the
      G(0)/G(1) phase of the cell cycle and re-stimulated by carbachol or epidermal
      growth factor. These results suggest that OP insecticides and their oxons affect
      astroglial cell proliferation and that the transition from the G(0)/G(1) to the
      S/G(2) phase of the cell cycle may be particularly sensitive to the action of
      these compounds.

PMID- 16102885
TI  - Erythrocyte aggregation is increased in preterm premature rupture of the
      membranes.
AB  - OBJECTIVE: To asses the degree of erythrocyte aggregation in the peripheral blood
      of women with preterm premature rupture of the membranes (PPROM). STUDY DESIGN:
      This was a prospective case control study. Twenty patients with preterm premature
      rupture of the membranes and matched controls were recruited at the Lis Maternity
      Hospital. A slide test and image analysis were used to quantitate the degree of
      erythrocyte aggregation. Hematological indices and markers of inflammation such
      as the erythrocyte sedimentation rate and C-reactive protein were also compared.
      RESULTS: The vacuum radius (VR) of the study group was significantly higher than
      in the control group at 14.8+/-1.6 microm versus 10.0+/-1.0 microm, respectively
      (P=0.03). Other hematological indices were not changed significantly between the
      groups. CONCLUSIONS: We found an increase in erythrocyte aggregation in the
      peripheral blood of patients with preterm premature rupture of the membranes. We
      used this sensitive marker of inflammation to further support the theory that
      PPROM is an inflammatory state.

PMID- 16102886
TI  - A polymorphism of the plasminogen activator inhibitor-1 gene promoter and the
      polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the association of a common 5G/4G polymorphism of the
      plasminogen activator inhibitor-1 gene (PAI1) with occurrence and clinical
      characteristics of the polycystic ovary syndrome (PCOS). STUDY DESIGN: In a case
      control study, we evaluated a series of 106 Caucasian women with PCOS and 102
      healthy controls. Women completed a detailed questionnaire and underwent a
      peripheral venous puncture, ultrasonography, and a standardized oral glucose
      tolerance test (OGTT). The PAI1 gene promoter polymorphism was evaluated using
      PCR. RESULTS: Allele and genotype frequencies were not significantly different
      among women with PCOS and controls (P=0.3 and 0.6, respectively). In women with
      PCOS, presence of the 5G/4G polymorphism of PAI1 was not associated with changes
      in serum hormone levels or with clinical characteristics. CONCLUSIONS: The 5G/4G
      polymorphism of the PAI1 promoter is not associated with occurrence and phenotype
      of the PCOS.

PMID- 16102887
TI  - Radical resection of invasive endometriosis with bowel or bladder involvement-
      long-term results.
AB  - OBJECTIVE: With the present study we wanted to evaluate the effect of a radical
      resection of bowel and bladder endometriosis with respect to relief of pain
      symptoms and long-term effects. STUDY DESIGN: Retrospectively we analyzed 23
      patients undergoing bowel or bladder resection for infiltrating endometriosis
      between 1995 and 2004. Chart review was performed and data were analyzed with
      respect to pain symptoms, fertility, type of surgery, operative morbidity and
      mortality. At 1, 3 and 5 years of follow-up patients were asked to evaluate their
      symptoms based on a visual analogue pain scale (0: no pain, 10: most severe
      pain). Results were compared using the Student's t-test. RESULTS: Leading
      symptoms were chronic pelvic pain (17/23, 73.9%), dysmenorrhea (11/23, 47.8%),
      dyspareunia (6/23, 26.1%), infertility (4/23, 17.4%) and dyschezia (4/23, 17.4%).
      Three patients (13%) had abdominal hysterectomy, 5 (21.7%) LSO (n = 2) or BSO (n
      = 3), 18 (78.3%) anterior rectal resection, 4 (17.4%) sigmoid resection, 2 (8.6%)
      segmental bladder resection and one patient (4.3%) cecal resection. Major
      complications requiring re-operation occurred in three patients (2x postoperative
      bleeding, 1x anastomosis break-down). During follow-up (mean 40.5 months) 21 of
      the 23 patients (91.3%) had a persistent improvement of symptoms, 8 of the 23
      (34.8%) had recurrent symptoms with a mean symptom-free interval of 40.4 months
      after surgery (24-60 months). No patient developed dyspareunia or dyschezia
      during follow-up. Overall cure rate was 73.9%. Four patients became pregnant
      (23%). Average pain scores increased during follow-up period but still remained
      significantly below the initial score (p < 0.001). CONCLUSION: Radical surgery
      for deep endometriosis with bowel or bladder involvement leads to a reliable and
      persistent relief of pain symptoms. Especially deep dyspareunia and dyschezia
      might be eliminated by this procedure.

PMID- 16102888
TI  - Enhancement in biodegradability of distillery wastewater using enzymatic
      pretreatment.
AB  - A combined treatment technique consisting of enzymatic hydrolysis, followed by
      aerobic biological oxidation was investigated for the treatment of alcohol
      distillery spent wash. The enzyme cellulase was used for the pretreatment step
      with an intention of transforming the complex and large pollutant molecules into
      simpler biologically assimilable smaller molecules. Batch experiments were
      performed in order to analyze the influence of various parameters like
      pretreatment time, enzyme concentration and pH during the pretreatment step on
      the subsequent aerobic oxidation kinetics. The rate of aerobic oxidation was
      enhanced by 2.3 fold for the pretreated sample as compared to the untreated
      sample when the pH during the pretreatment step was maintained at a value of 4.8.
      Similarly, a two fold increase in the aerobic oxidation rate was found when the
      effluent was pretreated with the enzyme, without any pH control (i.e. effluent pH
      of 3,8). The study indicated that the enzymatic pretreatment of the effluent
      could be one of the successful pretreatments which can lead to enhancement of the
      rate of the subsequent aerobic oxidation.

PMID- 16102889
TI  - Prolonged herbicide-induced vegetation changes in a regenerating boreal aspen
      clearcut.
AB  - A soil-active herbicide (hexazinone) was applied (0, 2, and 4 kg/ha of active
      ingredient) in a 3-year-old regenerating boreal Populus tremuloides Michx.
      (aspen) clearcut to determine its effect on the compositional and structural
      development of the vegetation. Woody stem densities and plant foliar cover were
      evaluated prior to and 2, 6, and 17 years after treatment. Herbicide treatment at
      the 2 and 4 kg/ha rates reduced tree and total woody stem densities relative to
      the 0 kg/ha level. The 4 kg/ha level reduced stem densities by 27% 17 years after
      treatment. The primary reductions occurred in Amelanchier alnifolia (Nutt.) Nutt.
      ex M. Roemer (saskatoon) and Rosa acicularis Lindl. (wild rose); whereas Corylus
      cornuta Marsh. (beaked hazelnut) and Viburnum edule (Michx.) Raf. (low-bush
      cranberry) stem densities increased. Notable herbicide-caused foliar cover
      reductions at the 4 kg/ha level occurred in Eurybia conspicua (Lindl.) Nesom.
      (showy aster), Mertensia paniculata (Ait.) G. Don. (tall mertensia), Rubus
      pubescens Raf. (dewberry), and Spiraea betulifolia Pallas (spiraea), but Aralia
      nudicaulis L. (sarsaparilla), Cornus canadensis L. (bunchberry), and
      Symphyotrichum ciliolatum (Lindl.) A.&D. Lve (Lindley's aster) increased. Less
      distinctive but similar changes occurred in the 2 kg/ha treatment. Total plant
      cover, species richness, and species dominance concentration were similar among
      treatments. Eight distinctive forest understory-types were recognized among
      treatments in Year 17. Between the 0 and 4 kg/ha treatments, five understory
      types differed in their frequency of occurrence. Hexazinone did not improve the
      survival of silviculturally planted Picea glauca (Moench) Voss (white spruce)
      seedlings relative to untreated sites, but the 4 kg/ha treatment level did
      increase Pinus contorta Dougl. ex Loud. (lodgepole pine) survival from 12 to 34%.
      Surviving seedlings had significantly greater height and basal diameter growth
      than those at the 0 kg/ha sites, particularly the 4 kg/ha treatment.

PMID- 16102890
TI  - Selecting small reserves in a human-dominated landscape: a case study of Hong
      Kong, China.
AB  - In this case study of a degraded tropical landscape, we examine how the protected
      area system in Hong Kong, China, should be modified to improve its efficiency in
      protecting the surprisingly rich biota. The challenge lies in the fine scale of
      site selection, and the absence of a core area with high species richness and
      rarity. Site selection was first conducted in 1 km grid units by selecting
      hotspots and irreplaceable sites using field records for eight groups of species
      (amphibians, reptiles, mammals, breeding birds, ants, butterflies, dragonflies
      and rare vascular plants). The habitats of conservation value within the selected
      grid units were then delineated on the basis of expert knowledge. Recommendations
      for increasing the total existing protected area by 6% (i.e. an additional 2% of
      Hong Kong's total land area) were submitted to the Government in August 2000. To
      test the robustness of the results, site selection was repeated in 2001 using
      updated data and different selection methods. The numbers of squares selected by
      complementarity-based algorithms were similar to those by the hotspots and
      irreplaceable site method. Sites selected for rare species were very sensitive to
      data completeness, implying that the application of complementarity-based
      algorithms at fine scales might be limited.

PMID- 16102891
TI  - Prescribed burning effects on summer elk forage availability in the subalpine
      zone, Banff National Park, Canada.
AB  - The effects of prescribed burning on forage abundance and suitability for elk
      (Cervus elaphus) during the snow-free season was evaluated in east-central Banff
      National Park, Canada. Six coniferous forest and mixed shrub-herb plant
      communities (n=144 plots), and 5223ha of burned (n=131) vegetation <12 years old
      were sampled using a stratified semi-random design. Sampling units represented
      various combinations of vegetation, terrain conditions, and stand ages that were
      derived from digital biophysical data, with plant communities the basic unit of
      analysis. Burning coniferous forest stands reduced woody biomass, and increased
      herbaceous forage from 146 to 790 kg/ha. Increases commonly occurred in the
      percent cover of hairy wild rye (Leymus innovatus (Beal) Pigler) and fireweed
      (Chamerion angustifolium (L.) Holub.). The herbaceous components of mixed shrub
      herb communities increased from 336-747 kg/ha to 517-1104 kg/ha in response to
      burning (P<0.025, Mann-Whitney U-test). Browse biomass (mostly Salix spp. and
      Betula nana L.) increased >or=220% (P<or=0.003, Mann-Whitney U-test) from 653
      kg/ha in deciduous shrub types. Elk preferences for unburned and burned
      vegetation-types were assessed as low and moderate, respectively. Potential
      summer carrying capacity, based on forage availability, increased from eight to
      28 elk/100 km2 within burned areas, whereas spring grazing potential rose from 13
      to 45 elk/100 km2. Most of the increase (73%) was attributable to changes within
      burned Engelmann Spruce stands, which composed 58% of the burned area.

PMID- 16102892
TI  - Toward a theory of evolutionary computation.
AB  - We outline a theory of evolutionary computation using a formal model of
      evolutionary computation--the Evolutionary Turing Machine--which is introduced as
      the extension of the Turing Machine model. Evolutionary Turing Machines provide a
      better and a more complete model for evolutionary computing than conventional
      Turing Machines, algorithms, and Markov chains. The convergence and convergence
      rate are defined and investigated in terms of this new model. The sufficient
      conditions needed for the completeness and optimality of evolutionary search are
      investigated. In particular, the notion of the total optimality as an instance of
      the multiobjective optimization of the Universal Evolutionary Turing Machine is
      introduced. This provides an automatic way to deal with the intractability of
      evolutionary search by optimizing the quality of solutions and search costs
      simultaneously. Based on a new model a very flexible classification of
      optimization problem hardness for the evolutionary techniques is proposed. The
      expressiveness of evolutionary computation is investigated. We show that the
      problem of the best evolutionary algorithm is undecidable independently of
      whether the fitness function is time dependent or fixed. It is demonstrated that
      the evolutionary computation paradigm is more expressive than Turing Machines,
      and thus the conventional computer science based on them. We show that an
      Evolutionary Turing Machine is able to solve nonalgorithmically the halting
      problem of the Universal Turing Machine and, asymptotically, the best
      evolutionary algorithm problem. In other words, the best evolutionary algorithm
      does not exist, but it can be potentially indefinitely approximated using
      evolutionary techniques.

PMID- 16102893
TI  - "Frontal variant Alzheimer's disease": a reappraisal.
AB  - Two cases of clinically diagnosed sporadic Alzheimer's disease with early and
      prominent behavioural features (social disinhibition, emotional blunting,
      stereotyped verbal utterances) sufficient to prompt an initial diagnosis of
      frontotemporal dementia are presented. It is suggested that the term "frontal
      variant AD" be used for this clinically defined phenotype, which has also been
      described in cases of inherited AD associated with certain presenilin-1 gene
      mutations. This differs from previous usage of the term "frontal variant AD" to
      describe AD with predominant frontal lobe neuropathological change (although the
      clinical phenotype may reflect regional distribution of pathology), but parallels
      the clinical definition of visual agnosic, aphasic and apraxic presentations of
      AD. The proposed usage would also emphasise differential diagnosis.

PMID- 16102894
TI  - Transient tetraplegia after cervical facet joint injection for chronic neck pain
      administered without imaging guidance.
AB  - We report about a patient in whom transient tetraplegia with intact
      proprioception occurred immediately after infiltration of a facet joint at the C6
      level guided by anatomical landmarks. After positioning the patient supine and
      applying atropine and oxygen, respiration and circulation were stable and all
      symptoms resolved within the next 30 min. The type of neurological pattern and
      the course of disease suggest an inadvertent injection into a cervical radicular
      artery that reinforces the anterior spinal artery. This complication is
      potentially serious and may be permanently disabling or life threatening. It
      should be considered by any clinician performing "blind" zygapophysial joint
      injections in the cervical spine. Using imaging guidance should help prevent this
      type of complication.

PMID- 16102895
TI  - Thin corpus callosum and amyotrophy in spastic paraplegia--case report and review
      of literature.
AB  - We report the clinical, structural, functional and genetic characterization of a
      37-year-old Caucasian female, presenting as a sporadic case of complicated
      spastic paraplegia with thin corpus callosum (CC), cognitive impairment,
      amyotrophy of the hand muscles and a sensorimotor neuropathy and review the
      literature for spastic paraplegia with thin CC. Magnetic resonance imaging (MRI)
      examination revealed a thin CC with fronto-parietal cortical atrophy.
      18Fluordesoxyglucose positron emission tomography (FDG-PET) showed reduced
      cortical and thalamic metabolism. By transcranial magnetic stimulation, we
      delineated a severe impairment of transcallosal inhibition. Sequence analysis did
      not reveal disease causing mutations in the genes SLC12A6 (Andermann), Spastin
      (SPG 4), BSCL2 (SPG 17) and Spartin (SPG 20). We reviewed the literature for HSP
      with thin CC and found 113 HSP patients with thin CC previously described (35
      with linkage to chromosome 15q13-15). Thin CC and peripheral neuropathy often
      appear together in spastic paraplegia and might be indicative for combined
      degeneration mechanism of central and peripheral axons.

PMID- 16102896
TI  - Prognostic impact of p53 protein overexpression in patients with node-negative
      lung adenocarcinoma.
AB  - Prognostic value of p53 protein expression in node-negative lung adenocarcinoma
      is still controversy. The expression of p53 protein was examined
      immunohistochemically in lung adenocarcinoma using monoclonal antibody BP53-12. A
      total 131 cases of primary lung adenocarcinoma were examined. Relationship
      between expression of p53 protein and clinicopathologic factors were studied.
      Overexpression of p53 protein was found in 19 patients (14.5%). Univariate and
      multivariate analysis showed that overexpression of p53 protein was an
      independent prognostic factor in node-negative lung adenocarcinoma. p53
      alteration could be a valuable predictor for prognosis in node-negative lung
      adenocarcinoma.

PMID- 16102897
TI  - The assessment of risk caused by domino effect in quantitative area risk
      analysis.
AB  - A systematic procedure for the quantitative assessment of the risk caused by
      domino effect was developed. Escalation vectors, defined as the physical effects
      responsible of possible accident propagation, were identified for the primary
      scenarios usually considered in the QRA procedure. Starting from the assessment
      of the escalation vectors, the methodology allows the identification of credible
      domino scenarios and the estimation of their expected severity. A simplified
      technique was introduced for consequence and vulnerability assessment of domino
      scenarios. The overall contribution of domino effect to individual risk, societal
      risk and to the potential life loss index was calculated by a specific procedure,
      taking into account all the credible combinations of secondary events that may be
      triggered by each primary scenario. The development of a software package allowed
      the application of the procedure to several case-studies. The results evidenced
      the relevant modifications of the risk indexes caused by domino effect and the
      importance of including the quantitative analysis of domino effect in QRA, in
      order to correctly assess and control the risk caused by escalation scenarios.

PMID- 16102898
TI  - Electrocoagulation of methylene blue and eosin yellowish using mild steel
      electrodes.
AB  - The paper presents the study of electrocoagulation (EC) of aqueous dye solutions
      of two different industrial dyes in a batch stirred cell. Experiments were
      carried out with 200 mg/l individual concentration of methylene blue (MB) and
      eosin yellowish (EY) in presence of NaCl as electrolyte. Effect of operating time
      and current density on the decolorization of dye solutions, reduction of chemical
      oxygen demand (COD) and variation in conductivity, pH during treatment has been
      studied. Small difference between color diminution and COD reduction has been
      found with the progress of treatment. First-order rate equation for dye removal
      has been developed from the experimental results. Sludge formation during EC and
      problems associated with this solid waste generation and disposal has been
      assessed. Energy consumption in KWh/m(3) with reduction of COD (kg) during
      treatment has been reported. Electric power consumption of 1.5 KWh reduces 0.21
      and 0.11 kg COD from 0.24 and 0.14 kg of initial COD for MB and EY, respectively,
      starting from 200 mg/l dye concentration.

PMID- 16102899
TI  - Activity of adenylyl cyclase and protein kinase A contributes to morphine-induced
      spinal apoptosis.
AB  - Our previous study has shown that chronic morphine exposure induces neuronal
      apoptosis within the spinal cord dorsal horn; however, the mechanisms of morphine
      induced apoptosis remain unclear. Here we examined whether adenylyl cyclase (AC)
      and protein kinase A (PKA) would play a role in this process. Intrathecal
      morphine regimen (10 microg, twice daily x 7 days) that resulted in
      antinociceptive tolerance induced spinal apoptosis as revealed by in situ
      terminal deoxynucleotidyl transferase (TdT)-UTP-biotin nick end labeling (TUNEL).
      The TUNEL-positive cells were detected primarily in the superficial laminae of
      the spinal cord dorsal horn, which was associated with an increase in the
      expression of activated caspase-3 and mitogen-activated protein kinase (MAPK)
      within the same spinal region. Co-administration of morphine with a broad AC
      inhibitor (ddA), a PKA inhibitor (H89), or a MAPK inhibitor (PD98059)
      substantially reduced the number of TUNEL-positive cells, as compared with the
      morphine alone group. The results indicate that the spinal AC and PKA pathway
      through intracellular MAPK may be contributory to the cellular mechanisms of
      morphine-induced apoptosis.

PMID- 16102900
TI  - Lumbar extensor fatigue and circumferential ankle pressure impair ankle joint
      motion sense.
AB  - Fatigue of the lumbar extensor muscles has been associated with a degradation of
      balance, but the mechanism is not well understood. The ankle plays a major role
      in upright standing, and loss of proprioceptive acuity at the ankle could
      contribute to a degradation of balance. Therefore, the first objective of this
      study was to investigate the effect of lumbar extensor fatigue on ankle
      proprioceptive acuity. The second objective was to investigate the effect of
      circumferential ankle pressure (CAP) on ankle proprioceptive acuity to evaluate
      CAP as a potential intervention to mitigate any loss of proprioceptive acuity at
      the ankle with lumbar extensor fatigue. To address these objectives, ankle joint
      motion sense was evaluated with and without CAP, both before and after the lumbar
      extensors were fatigued. Results showed an impairment in joint motion sense with
      both fatigue and CAP. These results indicate that lumbar extensor fatigue impairs
      ankle proprioceptive acuity, which may help explain observed increases in
      postural sway subsequent to lumbar extensor fatigue.

PMID- 16102901
TI  - An in vitro model of inflammatory neurodegeneration and its neuroprotection.
AB  - Inflammation has been implicated in a variety of acute and chronic
      neurodegenerative diseases in which the inflammatory processes are considered not
      only to result from neurodegenerative effects, but also to contribute to these
      effects. To investigate the primary effect of inflammation on neuronal survival,
      a co-culture system of neuronal cells (differentiated SH SY5Y human neuroblastoma
      cells or primary cortical/striatal neurons) and monocytic cells (THP-1) in direct
      cell-cell contact was set up. After 5 days, THP-1 activation by
      lipopolysaccharide and phorbol 12-myristate 13-acetate resulted in a significant
      increase of neuronal cell death compared to co-culture without activation. In
      neuroprotection studies using this model, ascorbic acid and EDTA demonstrated a
      highly significant reduction in activated THP-1 induced cell death. Glutathione
      and NBQX, but not the protease inhibitor, PMSF, and catalase, also significantly
      reduced this inflammatory neurotoxicity. Indomethacin was protective of the
      primary cultured neurons but not the SH SY5Y cells. This co-culture of neuronal
      cells and activated THP-1 provides a useful model for the study of inflammatory
      mechanisms resulting in neuronal cell death.

PMID- 16102902
TI  - Functional alteration of inhibitory influences on spinal motor output in painful
      diabetic neuropathy in rats.
AB  - Diabetes is frequently accompanied by painful polyneuropathies that are mediated
      by enhanced neuronal excitability in the spinal cord, partly because of decrease
      in spinal intrinsic inhibitory influences. Changes in spinal excitatory
      inhibitory balance may alter spinal segmental motor output. In the study
      presented here, the mono- and disynaptic (the fastest polysynaptic) reflexes (MSR
      and DSR, respectively) were recorded from L5 ventral roots in response to
      stimulation of the ipsilateral L5 dorsal root in spinalized streptozotocin (STZ)
      induced diabetic rats with a reduced withdrawal threshold to mechanical stimuli.
      The diabetic rats generally exhibited larger spinal reflex amplitudes, the DSR
      being influenced in particular. We addressed whether recurrent and presynaptic
      inhibition of the spinal reflexes were altered in STZ-treated animals. The
      recurrent inhibition of the MSR and DSR elicited by preceding antidromic
      conditioning stimulation delivered to the recorded L5 ventral root was markedly
      suppressed in diabetic rats. By contrast, the presynaptic inhibition of the MSR
      and DSR elicited by preceding conditioning stimulation to the ipsilateral L4
      dorsal root was not impaired. Thus, in diabetic painful neuropathy, reduced
      spinal intrinsic inhibition in the ventral horn contributes to an enhanced spinal
      segmental motor output.

PMID- 16102903
TI  - The dardarin G 2019 S mutation is a common cause of Parkinson's disease but not
      other neurodegenerative diseases.
AB  - Mutations in the leucine-rich kinase 2 gene (LRRK 2) encoding dardarin, on
      chromosome 12, are a common cause of familial and sporadic Parkinson's disease.
      The most common mutation, a heterozygous 6055 G>A transition (G 2019 S) accounts
      for approximately 3--10% of familial Parkinson's disease and 1--8% sporadic
      Parkinson's disease in several European-derived populations. Some families with
      disease caused by LRRK 2 mutations have been reported to include patients with
      highly variable clinical and pathological features. We screened for the most
      common LRRK 2 mutation in a series of patients with Parkinson's Disease,
      Alzheimer's disease, Progressive Supranuclear Palsy, Multiple System Atrophy and
      frontotemporal dementia, as well as in neurologically normal controls. The
      mutation was found only in Parkinson's disease patients or their relatives and
      not in those with other neurodegenerative disease.

PMID- 16102904
TI  - Synthesis and characterization of a novel DTPA polymerized hemoglobin based
      oxygen carrier.
AB  - OBJECTIVE: The purpose of this study was to prepare a novel polymerized
      hemoglobin (Hb) based oxygen carrier (HBOC) designed to minimize Hb induced
      hypertension, while employing a simple and inexpensive method of preparation.
      Cyclic-diethylenetriaminepentaacetic acid (DTPA) was used to polymerize stroma
      free Hb (SF-Hb). METHODS: SF-Hb was isolated from red blood cells and reacted
      with DTPA at a constant concentration, pH, and duration. Low molar mass fractions
      (<100 kDa) were removed using ultrafiltration. Reactions and subsequent
      ultrafiltration steps were determined to be reproducible by analyzing molar mass,
      colloid osmotic pressure and oxygen affinity. Finally, a model of 50% exchange
      transfusion (ET) in rats was used to evaluate the blood pressure response to DTPA
      polymerized SF-Hb (Poly-DTPA-Hb). RESULTS: Poly-DTPA-Hb demonstrated a number
      averaged molar mass of 128.7 kDa and a weighted average of 223.0 kDa. Oxygen
      binding equilibrium indicated high oxygen affinity (P50 = 5.1+/-0.01 mm Hg) and
      little cooperativity (n = 1.4). Poly-DTPA-Hb and a control DTPA polymerized human
      serum albumin (Poly-DTPA-HSA) unexpectedly caused acute hypotension during the
      period of ET in rats (mean arterial pressure approximately 45% less than
      baseline). Hypotension occurring over the period of ET was determined to be
      mediated by calcium binding to protein associated DTPA. This effect was
      attenuated by the addition of calcium chloride (CaCl2) to the Poly-DTPA protein
      preparations. CONCLUSIONS: Cyclic DTPA anhydride can be used to create cross
      linked and polymerized hemoglobin, using a simple and inexpensive process.
      However, the addition of CaCl2 to the preparation appears to be required to
      prevent calcium chelation and subsequent hypotension during infusion.

PMID- 16102905
TI  - Acute phase and five-year follow-up study of fluoxetine in adolescents with major
      depression and a comorbid substance use disorder: a review.
AB  - This paper reviews the results of an acute phase trial and a five-year follow-up
      study of fluoxetine in adolescents with major depression and a substance use
      disorder (SUD). This study included a 12-week open label acute phase study of 13
      comorbid adolescents, followed by comprehensive assessments conducted 1, 3, and 5
      years after entry into an acute phase fluoxetine trial. The results of the acute
      phase study and of the 1, 3, and 5-year follow-up assessments have already been
      published in four papers. The current paper was designed to cover the results of
      the study across the entire 5-year time spectrum of the study, and to summarize
      the clinical results across that entire time period. The data from this pilot
      study suggest that the long-term (5-year) clinical course for the Alcohol
      Dependence, Cannabis Dependence, and academic functioning of comorbid adolescents
      following acute phase treatment with SSRIs is generally good. However, the long
      term clinical course for the Major Depression of that comorbid adolescent
      population is surprisingly poor.

PMID- 16102906
TI  - Interaction between isolation rearing and social development on exploratory
      behavior in male rats.
AB  - The effect of isolation on exploratory behavior has been shown to differ
      depending on the developmental stages of male rats. However, there has been
      little systematic comparison of the frequencies and the patterns of exploratory
      behavior across the developmental stages. The present study assessed the
      frequencies of exploration using the emergence test and exploratory patterns in
      the open-field test in three developmental stages of male rats: juvenile, post
      puberty, and adult. A lower propensity for exploration was observed in rats
      isolated during the juvenile stage, as assessed by increased latency and
      decreased duration of exploratory behaviors compared to pair-reared rats, and
      this tendency was maintained in adulthood. Altered patterns of exploratory
      behavior were demonstrated both in rats isolated in adulthood, who showed an
      increased active pattern, and those pair-reared following puberty, who shifted to
      a more passive pattern. However, rats isolated during the juvenile stage did not
      change their exploratory patterns following puberty. These results suggest that
      the changes in the exploratory pattern, which can be observed in adulthood, are
      associated with the emergence of adult-like dominance relationships. Juvenile
      isolated rats did not show these changes following puberty, suggesting the
      importance of social interaction as juveniles for the ontogenetic emergence of
      behavioral flexibility implicated in the regulation of exploratory patterns.

PMID- 16102907
TI  - Testing resource value in group-housed animals: an investigation of cage height
      preference in laying hens.
AB  - To avoid unpredictable social effects, animals' behavioural priorities are almost
      always tested using individuals housed singly, yet many species kept commercially
      are social animals housed in groups. Our aim was to develop a method of
      investigating environmental preference in group-housed laying hens, Gallus gallus
      domesticus, that maximised the external validity of our findings. In a simple
      test of preference, eight groups of ten hens were given free choice between
      furnished cages with minimum heights of 38 cm (low) and 45 cm (high). A
      preference for one cage height over the other would be evident as a shift from a
      binomial distribution of flock sizes in the two cages. No height preference was
      found as hens distributed evenly between the two cages more frequently than was
      expected. This suggests at high stocking densities maximising average inter
      individual distance could be a priority over increased cage height. In a second
      experiment, to investigate the value that hens placed on a change in cage height;
      a 'cost' in the form of a narrow gap was imposed on movement from a low or high
      start cage to a high or low target cage, respectively. Cage height did not
      influence the latency of the first three hens to enter the target cage. However,
      latencies for subsequent hens were shorter and more hens worked to access a high
      target cage than a low target cage. We suggest that titrating animals'
      willingness to tolerate higher stocking densities against access to a resource
      could be an effective way to compare responses of group-housed animals to
      resources that are expected to satisfy the same motivational state.

PMID- 16102908
TI  - Treatment of methadone-maintained patients with adult ADHD: double-blind
      comparison of methylphenidate, bupropion and placebo.
AB  - The purpose of this double-blind, three-arm, 12-week trial was to compare the
      efficacy of sustained-release methylphenidate or sustained-release bupropion to
      placebo in treating adult attention deficit hyperactivity disorder (ADHD)
      symptoms. The randomized sample consisted of 98 methadone-maintained patients who
      were pre-dominantly male (57%) and 40% Caucasian, 40% Hispanic and 20% African
      American. All participants met DSM-IV criteria for adult ADHD, with 53% meeting
      DSM-IV criteria for cocaine dependence/abuse. In addition to medication and
      treatment as usual at a methadone program, individuals received weekly individual
      cognitive behavioral treatment. Other than current employment status, there were
      no significant demographic differences across the three treatment groups. Seventy
      percent completed the 12-week trial. There were no differences in retention rate
      based on treatment group. A reduction in ADHD symptoms using the adult ADHD
      rating scale was observed in all three groups, but there were no significant
      differences in outcome between treatments. The placebo response rate was high,
      with 46% of the placebo group self-reporting substantial improvement in their
      ADHD symptoms (>30% reduction in adult ADHD rating scale). Using other ADHD
      outcome measures, the placebo response and medication response rates were
      substantially lower. There was no evidence of misuse of medication or worsening
      of cocaine use among those randomized to methylphenidate. Taken together,
      sustained-release methylphenidate or sustained-release bupropion did not provide
      a clear advantage over placebo in reducing ADHD symptoms or additional cocaine
      use in methadone-maintained patients.

PMID- 16102909
TI  - Analysis of genes involved in methyl halide degradation in Aminobacter
      lissarensis CC495.
AB  - Aminobacter lissarensis CC495 is an aerobic facultative methylotroph capable of
      growth on glucose, glycerol, pyruvate and methylamine as well as the methyl
      halides methyl chloride and methyl bromide. Previously, cells grown on methyl
      chloride have been shown to express two polypeptides with apparent molecular
      masses of 67 and 29 kDa. The 67 kDa protein was purified and identified as a
      halomethane:bisulfide/halide ion methyltransferase. This study describes a single
      gene cluster in A. lissarensis CC495 containing the methyl halide utilisation
      genes cmuB, cmuA, cmuC, orf 188, paaE and hutI. The genes correspond to the same
      order and have a high similarity to a gene cluster found in Aminobacter ciceronei
      IMB-1 and Hyphomicrobium chloromethanicum strain CM2 indicating that genes
      encoding methyl halide degradation are highly conserved in these strains.

PMID- 16102910
TI  - Multiple restriction-modification systems are present in rumen treponemes.
AB  - Type II restriction endonucleases were purified by heparin-sepharose followed by
      ion chromatography from Treponema strains. The results indicate that in addition
      to frequently cutting GATC-specific restriction enzymes, the tested strains also
      possess rarely cutting endonucleases. The purified restriction endonucleases
      represent four different sequence specificities, comprising isoschizomers of
      DrdI, AflII, Tth111I and NdeI. The data presented show that three rumen Treponema
      strains possess altogether seven type II restriction-modification systems. Thus,
      individual Treponema strains may be considered an interesting source of multiple
      type II restriction enzymes.

PMID- 16102911
TI  - Xanthomonas albilineans HtpG is required for biosynthesis of the antibiotic and
      phytotoxin albicidin.
AB  - Xanthomonas albilineans, the causal agent of leaf scald disease of sugarcane,
      produces a highly potent polyketide-peptide antibiotic and phytotoxin called
      albicidin. Previous studies established the involvement of a large cluster of
      genes in the biosynthesis of this toxin. We report here the sub-cloning and
      sequencing of an additional gene outside of the main cluster and essential for
      albicidin biosynthesis. This gene encodes a 634-amino-acid protein that shows
      high identity with the Escherichia coli heat shock protein HtpG. Complementation
      studies of X. albilineans Tox- mutants confirmed the requirement of htpG for
      albicidin biosynthesis and revealed functional interchangeability between E. coli
      and X. albilineans htpG genes. HtpG was co-localised with albicidin in the
      cellular membrane, i.e., the cellular fraction where the toxin is most probably
      biosynthesised. Here we show the requirement of an HtpG protein for the
      biosynthesis of a polyketide-peptide antibiotic.

PMID- 16102912
TI  - Cytotoxic and antimicrobial metabolites from marine lignicolous fungi, Diaporthe
      sp.
AB  - A new compound (1), named diaporthelactone, together with two known compounds (2
      and 3) were isolated from the culture of Diaporthe sp., a marine fungus growing
      in the submerged rotten leaves of Kandelia candel in the mangrove nature
      conservation areas of Fugong, Fujian Province of China. The new compound was
      elucidated to be 1,3-dihydro-4-methoxy-7-methyl-3-oxo-5-isobenzofuran
      carboxyaldehyde (1), which showed cytotoxic activity against KB and Raji cell
      lines (IC50 6.25 and 5.51 microg mL(-1), respectively). Two known compounds, 7
      methoxy-4,6-dimethyl-3H-isobenzofuran-1-one (2) and mycoepoxydiene (3), were also
      demonstrated to exhibit cytotoxic activities for the first time. All three
      compounds were assessed for antimicrobial activity.

PMID- 16102913
TI  - LexA, a transcription regulator binding in the promoter region of the
      bidirectional hydrogenase in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The unicellular cyanobacterium Synechocystis PCC 6803 contains a single
      pentameric bidirectional hydrogenase encoded by hoxEFUYH. Transcriptional
      experiments demonstrated that the five hox genes are part of a single transcript
      together with three ORFs with unknown functions. The transcription start point
      was localized by 5' RACE to 168bp upstream the hoxE ATG start codon. DNA affinity
      assays demonstrated a specific interaction between the hox regulatory promoter
      region and a protein which, using mass spectrometry, was identified to be LexA.
      Overexpressed His-tagged Synechocystis LexA and EMSA showed a specific binding to
      the promoter region of the hox operon. Increasing concentrations of the purified
      LexA resulted in two retarded LexA-DNA complexes, in agreement with the presence
      of two putative LexA binding sites upstream the determined TSP.

PMID- 16102914
TI  - Toxicity testing of destruxins and crude extracts from the insect-pathogenic
      fungus Metarhizium anisopliae.
AB  - Increasing sensitivity towards secondary metabolites from fungal biological
      control agents (BCAs) has prompted the toxicological risk assessment of
      metabolites produced by the insect pathogenic fungus Metarhizium anisopliae.
      Viability studies on one human and one insect cell line were used to compare the
      two approaches of testing individual metabolites (destruxins A, B and E) or the
      complete crude extract from liquid cultures. Furthermore, crude extract was
      separated into fractions, which did not contain the main destruxins A, B and E.
      Evaluation of the cytotoxic activity of these different compounds suggested that
      a wide range of metabolites with synergistic or adverse effects are present in
      the crude extract. The results indicate that identification and toxicological
      assessment of each individual metabolite produced by a BCA is not only time and
      cost-intensive, but also does not convey the whole picture. Testing of the crude
      extract offers an alternative approach and is recommended when assessing the
      risks of metabolites for registration purposes.

PMID- 16102915
TI  - Analysis of hopQ alleles in East Asian and Western strains of Helicobacter
      pylori.
AB  - Helicobacter pylori hopQ (omp27) alleles exhibit a high level of genetic
      diversity, and certain hopQ genotypes have been associated with an increased risk
      for peptic ulcer disease. In this study, we analyzed hopQ alleles in H. pylori
      strains from East Asia and the United States. Phylogenetic analysis indicated the
      presence of two highly divergent families of hopQ alleles, without evidence of
      extensive recombination. Type I hopQ alleles from Western and Asian H. pylori
      strains were similar, and markedly different from type II hopQ alleles. Analyses
      of synonymous and non-synonymous nucleotide substitutions suggested that there is
      a positive selection for HopQ amino acid diversity. Type II hopQ alleles were
      identified commonly in Western H. pylori strains, but rarely in East Asian
      strains. Nearly all of the East Asian strains analyzed were cagA-positive and
      contained type I hopQ alleles. Geographic variation in the genetic
      characteristics of H. pylori strains may be a factor contributing to geographic
      variation in gastric cancer incidence.

PMID- 16102916
TI  - A genome-wide screening of BEL-Pao like retrotransposons in Anopheles gambiae by
      the LTR_STRUC program.
AB  - The advanced status of assembly of the nematoceran Anopheles gambiae genomic
      sequence allowed us to perform a wide genome analysis to looking at the presence
      of Long Terminal Repeats (LTRs) in the range of 10 kb by means of the LTR_STRUC
      tool. More than three hundred sequences were retrieved and 210 were treated as
      putative complete retrotransposons that were individually analysed with respect
      to known retrotransposons of A. gambiae and D. melanogaster. The results show
      that the vast majority of the retrotransposons analysed belong to the Ty3/gypsy
      class and only 8% to the Ty1/copia class. In addition, phylogenetic analysis
      allowed us to characterize in more detail the relationship of a large BEL-Pao
      lineage in which a single family was shown to harbour an additional env gene.

PMID- 16102917
TI  - A functional SNP in the promoter region of TCOF1 is associated with reduced gene
      expression and YY1 DNA-protein interaction.
AB  - Treacher Collins syndrome (TCS) is an autosomal dominant craniofacial
      malformation caused by null mutations in the TCOF1 gene. High inter and intra
      familial clinical variability, ranging from mild malar hypoplasia to perinatal
      death due to airway collapse is observed, but, to date, no genotype-phenotype
      correlation has been reported. Considering haploinsufficiency as the molecular
      mechanism underlying the disease, we have hypothesized that mutations in the
      promoter region of the gene, which has never been previously characterized, in
      trans with a pathogenic mutation, could modulate the phenotype. Therefore, the
      aims of the present study were to determine the TCOF1 gene's core promoter and to
      identify mutations in this region that could contribute to the phenotypic
      variation observed in this syndrome. We have delimitated the minimal promoter to
      a region of less than 150 bp, with 63% of identity among 5 different species. We
      screened 1.2 kbp of the TCOF1 5' flanking sequence in the DNA obtained from 21
      patients and 51 controls and identified four new single nucleotide polymorphisms
      (SNPs), one of which (-346C>T), was proved to be functional, as it decreased the
      promoter activity by 38%. Electrophoretic mobility shift assay (EMSA) analysis
      demonstrated that the -346T allele impairs DNA-binding to the YY1 transcription
      factor. This promoter variant represents a candidate allele to explain the
      clinical variability in patients bearing TCS.

PMID- 16102918
TI  - CHES1/FOXN3 interacts with Ski-interacting protein and acts as a transcriptional
      repressor.
AB  - Checkpoint Suppressor 1 (CHES1; FOXN3) encodes a member of the forkhead/winged
      helix transcription factor family. The human CHES1 cDNA was originally identified
      by its ability to function as a high-copy suppressor of multiple checkpoint
      mutants of Saccharomyces cerevisiae. Accumulating expression profile data suggest
      that CHES1 plays a role in tumorigenicity and responses to cancer treatments,
      though nothing is known regarding the transcriptional function of CHES1 or other
      FOXN proteins in human cells. In this report, we find that the carboxyl terminus
      of CHES1 fused to a heterologous DNA binding domain consistently represses
      reporter gene transcription in cell lines derived from tumor tissues. Using a
      cytoplasmic two-hybrid screening approach, we find that this portion of CHES1
      interacts with Ski-interacting protein (SKIP; NCoA-62), which is a
      transcriptional co-regulator known to associate with repressor complexes. We
      verify this interaction through co-immunoprecipitation experiments performed in
      mammalian cells. Further analysis of the CHES1/SKIP interaction indicates that
      CHES1 binds to a region within the final 66 hydrophobic residues of SKIP thus
      defining a new protein-protein interaction domain of SKIP. These data suggest
      that CHES1 recruits SKIP to repress genes important for tumorigenesis and the
      response to cancer treatments.

PMID- 16102919
TI  - Proceedings of the 4th International Symposium on Stallion Reproduction,
      Hannover, Germany, October 2005.

PMID- 16102920
TI  - Components in seminal plasma regulating sperm transport and elimination.
AB  - Seminal plasma has been suggested to be involved in sperm transport, and as a
      modulator of sperm-induced inflammation, which is thought to be an important part
      of sperm elimination from the female reproductive tract. This article reports on
      recent experiments on the importance of seminal plasma components in sperm
      transport and elimination. In Experiment 1, hysteroscopic insemination in the
      presence (n = 3) or absence (n = 3) of 2 ng/mL PGE showed an increased portion of
      spermatozoa crossing the utero-tubal junction in the presence of PGE in two
      mares, while no difference was observed between treatments in a third mare. In
      Experiment 2, whole seminal plasma, heat-treated seminal plasma (90 degrees C for
      45 min), and charcoal-treated seminal plasma were added to: (1) sperm samples
      during opsonization prior to polymorphonuclear neutrophil(s) (PMN)-phagocytosis
      assays (n = 5); or to (2) phagocytosis assays (n = 5). Opsonization of
      spermatozoa was suppressed in the presence of whole seminal plasma, compared with
      samples without seminal plasma (p < 0.05). Charcoal treatment did not remove the
      suppressive effect of seminal plasma on opsonization, but heat treatment of
      seminal plasma reduced its suppressive properties (p < 0.05). The addition of
      whole seminal plasma to opsonized spermatozoa almost completely blocked
      phagocytosis (p < 0.05). Charcoal treatment did not remove the suppressive effect
      of seminal plasma. However, heat-treated fractions of seminal plasma removed the
      suppressive effect of seminal plasma on phagocytosis (p < 0.05). In Experiment 3,
      viable and non-viable (snap-frozen/thawed) spermatozoa were subjected to in vitro
      assays for PMN binding and phagocytosis with the following treatments (n = 3):
      (1) seminal plasma (SP), (2) extender; (3) ammonium sulfate precipitated seminal
      plasma proteins with protease inhibitor (SPP+); or (4) ammonium sulfate
      precipitated seminal plasma proteins without protease inhibitor (SPP-). Treatment
      was observed to impact binding and phagocytosis of viable and non-viable
      spermatozoa (p < 0.05). SP and SPP+ suppressed PMN-binding and phagocytosis of
      viable sperm. This effect was also seen, but to a lesser degree, in SPP- treated
      samples. Non-viable spermatozoa showed less PMN-binding and phagocytosis than
      live sperm in the absence of SP. The addition of SP promoted PMN-binding and
      phagocytosis of non-viable spermatozoa. SPP- treated samples also restored PMN
      binding of non-viable spermatozoa. The addition of protease inhibitors removed
      this effect. In Experiment 4, seminal plasma proteins were fractionated based on
      MW by Sephacryl S200 HR columns (range 5000-250,000 kDa). Fractionated proteins
      were submitted to sperm-PMN binding assays. A protein fraction <35 kDa suppressed
      PMN-binding to live and snap-frozen spermatozoa. A greater MW protein fraction
      appeared to promote binding between PMNs and snap-frozen spermatozoa. While the
      addition of protease inhibitors was necessary to maintain the protective effect
      of seminal plasma proteins on viable spermatozoa, the promotive effect of seminal
      plasma on non-viable spermatozoa appeared to require some protease activity. It
      was concluded from these experiments that components of seminal plasma play
      active roles in transportation and survival of viable spermatozoa in the female
      reproductive tract and in the elimination of non-viable spermatozoa from the
      uterus.

PMID- 16102921
TI  - Applications of GnRH in the control and management of fertility in female
      animals.
AB  - Gonadotropin releasing hormone (GnRH) has long been recognized as a potential
      target for the control and management of fertility in female animals. Attempts to
      apply GnRH-based technology to manage fertility have focussed on the development
      of GnRH agonists, antagonists and vaccines. All of these methods have potential,
      but the widespread application of these technologies has been limited to date.
      The greatest advance in the use of GnRH-based technology for long-term fertility
      control in recent years has been the development and commercialization of depot
      formulations that release GnRH agonists for periods of up to 1 year. These
      products have a broad range of potential applications in production and domestic
      animal management. The further development and commercialization of GnRH vaccines
      has been hampered by the variability of response between individual animals. The
      need to use adjuvant and multiple boosters also make this a less attractive
      option than the current GnRH agonist technology. However, GnRH vaccines have the
      advantage that they do not induce the initial stimulatory response that follows
      GnRH agonist administration. GnRH antagonists and GnRH-toxin conjugates show
      promise but are in an earlier phase of development. To date, no depot or long
      acting formulations of antagonists have been developed. GnRH-toxin conjugates
      have yet to achieve permanent sterilization, but further dose-response trials may
      advance this approach.

PMID- 16102922
TI  - Assessment of drug permeability distributions in two different model skins.
AB  - Past in vitro studies with human skin have indicated that drug permeability
      coefficient (Kp) distributions do not always follow a Gaussian-normal pattern.
      This has major statistical implications, exemplified by the fact that use of t
      tests to evaluate significance is limited to normally distributed populations.
      Percutaneous absorption research often involves using animal or synthetic skins
      to simulate less readily available human skin. However, negligible work has been
      performed on assessing the permeability variabilities of these model membranes.
      This paper aims to fill this gap. To this end, four studies were undertaken
      representing two different drugs (caffeine and testosterone) with each drug
      penetrating through two different model skins (silicone membrane and pig skin).
      It was determined that in the silicone membrane studies, both compounds' Kp
      distributions could be fitted to a normal pattern. In contrast, in the pig skin
      studies, there were notable differences between each drug. While the testosterone
      Kp values could be fitted to a normal distribution, this was not possible with
      the caffeine Kp data, which could be fitted to a log-normal distribution. There
      is some evidence from the literature as well as physicochemical considerations
      that these outcomes may reflect general trends that are dependent upon both
      membrane and penetrant properties.

PMID- 16102923
TI  - Microwave processing of natural biopolymers--studies on the properties of
      different starches.
AB  - In this study, the influence of microwave irradiation on some physico-chemical
      properties and several pharmaceutical technological parameters of potato and
      maize starches was investigated. Changes in their habits were observed and
      decrease in moisture contents caused by the electromagnetic irradiation was
      determined. The crystalline structures and the micromorphological parameters of
      the starches were affected by microwave irradiation in different ways depending
      on the botanical origin of the samples. The tensile strengths of the compacts
      containing starches were decreased, their wetting properties were enhanced by the
      thermal process applied. Furthermore, microwave irradiation reduced the surface
      free energy and the polarity of the compacts significantly. Samples treated by
      conventional heating were used to compare the effects of microwave irradiation on
      the examined properties and parameters of these starches.

PMID- 16102924
TI  - Dissolution mechanism of poorly water-soluble drug from extended release solid
      dispersion system with ethylcellulose and hydroxypropylmethylcellulose.
AB  - The purpose of this study is to investigate the release mechanism of poorly water
      soluble drug from the extended release solid dispersion systems with water
      insoluble ethylcellulose (EC) and water-soluble hydroxypropylmethylcellulose
      (HPMC) (1:1). Indomethacin (IND) was used as a model of poorly water-soluble
      drug. Two kinds of solid dispersions were prepared by the solvent evaporation
      methods, which consist of the same formulation but exhibit different physical
      performance. It appeared that the dissolution behavior of IND depended on the
      structures of EC-HPMC matrices, which were governed by the preparation method. In
      addition, the dissolution behavior showed pH dependency that the dissolution rate
      of IND was slower in acidic medium than that in neutral medium. The experimental
      results revealed that the hydrophobic interaction between IND and EC occurred
      under lower pH and strongly delayed the dissolution rate of IND. The relationship
      between this hydrophobic interaction and the dissolution rate of IND was also
      proposed.

PMID- 16102925
TI  - Mechanisms of formation and disintegration of alginate beads obtained by
      prilling.
AB  - In this paper, compendial sodium alginate beads have been manufactured by laminar
      jet break-up technology. The effect of polymer concentration, viscosity and
      polymeric solution flow rate on the characteristics of beads was studied. Size
      distribution of alginate beads in the hydrated state was strongly dependent on
      the flow rate and viscosity of polymer solutions, since a transition from laminar
      jet break-up conditions to vibration-assisted dripping was observed. The re
      hydration kinetics of dried beads in simulated gastric fluid (SGF) showed that
      the maximum swelling of beads was reached after 1-2 h, with an increase in volume
      of two to three times and a time lag dependent on the polymer concentration. The
      re-hydration swelling profiles in simulated intestinal fluid (SIF) showed no time
      lag and higher swelling volume; moreover, in this medium after the maximum
      swelling was reached, the bead structure was quickly disaggregated because of the
      presence in the medium of phosphate able to capture calcium ions present in the
      alginate gel structure.

PMID- 16102926
TI  - Effects of water content in physical mixture and heating temperature on
      crystallinity of troglitazone-PVP K30 solid dispersions prepared by closed
      melting method.
AB  - Troglitazone, which possesses two asymmetric carbons, is obtained as a mixture of
      four isomers present in equal amounts. Troglitazone (Lot T003) has two melting
      points, about 120 and 175 degrees C. To increase the bioavailability of insoluble
      troglitazone, troglitazone-polyvinylpyrrolidone K30 (PVP) solid dispersions (SDs)
      were prepared with water by a unique closed melting method. In this study, the
      effects of the water content in the physical mixture (PM) and the heating
      temperature on the apparent crystallinity of troglitazone in SDs prepared by this
      method were investigated. When the water content in the PM was controlled at 3%,
      although the apparent crystallinity of troglitazone in the SD prepared by heating
      at 105 degrees C did not decrease (99%), that of the SDs prepared by heating at
      130 and 150 degrees C were reduced to 54 and 11%, respectively. This result
      indicated that the meltage of troglitazone varies depending on the heating
      temperature. The apparent crystallinity of troglitazone in the SDs decreased with
      increase in water content in the PM. In particular, SDs prepared by heating at
      130 and 150 degrees C showed 0% apparent crystallinity when the water content in
      the PM were more than 13 and 8%, respectively. When the heating temperature used
      was higher than the glass transition temperature of PVP plasticized with water,
      troglitazone crystals were dissolved in the rubbery PVP. Therefore, even if the
      heating temperature is lower than the melting point of troglitazone during
      preparation, controlling the water content in the PM at a high level can produce
      a troglitazone SD with 0% apparent crystallinity.

PMID- 16102927
TI  - Entrapment efficiency and release characteristics of polyethyleneimine-treated or
      -untreated calcium alginate beads loaded with propranolol-resin complex.
AB  - Propranolol-HCl-loaded calcium alginate (ALG) beads, propranolol-resin complex
      (resinate)-loaded calcium alginate (RALG) beads and polyethyleneimine (PEI)
      treated RALG (RALG-PEI) beads were prepared by ionotropic
      gelation/polyelectrolyte complexation method. The beads were evaluated and
      compared in respect of drug entrapment efficiency (DEE) and release
      characteristics in simulated gastric fluid (SGF, 0.1(N) HCl, pH 1.2) and
      simulated intestinal fluid (SIF, phosphate buffer, pH 6.8). DEE of RALG beads was
      considerably higher than that of ALG beads containing unresinated drug. However,
      DEE of RALG beads decreased with increase in both gelation time and concentration
      of the gel forming Ca2+ ions due to drug displacement from resinate. PEI
      treatment of RALG beads further decreased DEE as the polycation also displaced
      the drug from the resinate. The release of drug from all the beads was slow and
      incomplete in SGF owing to considerably less swelling of the beads and the
      decrease in drug release from the beads followed the order: RALG-PEI<RALG<ALG. In
      contrast to rapid discharge of the drug by ALG beads in SIF, RALG beads provided
      marginal prolongation in drug release as both ALG and RALG beads swelled and
      eroded rapidly although at different rates. On the other hand, drug release from
      RALG-PEI beads in SIF was considerably prolonged for different periods of time
      depending upon the conditions of PEI treatment. Interaction of the polycation
      with alginate resulted in the formation of polyelectrolyte complex membrane as
      evident from scanning electron microscopy (SEM), differential scanning
      calorimetry (DSC) and fourier-transform infrared spectroscopy (FTIR) studies. The
      membrane having reduced swelling and erosion properties behaved as a physical
      barrier to drug release. Kinetics of the drug release also confirmed the
      formation of physical barrier as anomalous transport type of release associated
      with. RALG beads tended to shift towards Fickian transport in case of RALG-PEI
      beads.

PMID- 16102928
TI  - High-pressure aerosol suspensions--a novel laser diffraction particle sizing
      system for hydrofluoroalkane pressurised metered dose inhalers.
AB  - In this study, a novel laser diffraction particle size analysis dispersion
      system, capable of sizing particles in situ within suspension hydrofluoroalkane
      (HFA) pressurised metered dose inhalers (pMDIs), was developed and tested. The
      technique was compared to four indirect particle sizing methods commonly used to
      determine the size of particles suspended in HFA pMDIs. The median volume
      diameter obtained using laser diffraction of both the salbutamol sulphate and
      fluticasone propionate suspended either in 2H, 3H-decafluoropentane or
      perfluoropentane (employed as surrogate propellants) was over one-order of
      magnitude larger than the particle sizes of the drugs suspended in HFA 134a. In
      contrast, the "in-flight" particle size using the Sympatec inhaler 2000 laser
      diffraction equipment undersized the particles, predicting higher delivery
      efficacy compared to the other sizing methods. However, the size of particles
      suspended in HFAs derived using the novel pressurised dispersion system, showed a
      linear correlation with the impaction results, r2=0.8894 (n=10). The novel
      pressure cell sizing technique proved to be simple to use, has the ability to be
      automated and was accurate, suggesting it could be an essential tool in the
      development of new suspension-based pMDI formulations.

PMID- 16102929
TI  - In vitro interactions of Aspilia africana (Pers.) C.D. Adams, a traditional
      antimalarial medicinal plant, with artemisinin against Plasmodium falciparum.
AB  - Traditional antimalarial medicinal preparations are widely used concurrently with
      antimalarial drugs in malaria endemic areas. The plant Aspilia africana (Pers.)
      C.D. Adams is commonly used for traditional treatment of malaria symptoms in East
      and Central Africa. An in vitro study of interactions between an extract from
      this plant with artemisinin against two strains of Plasmodium falciparum showed
      an antagonist relationship against both the chloroquine-sensitive D10 and the
      chloroquine- and sulphonamide-resistant K1 strains of Plasmodium falciparum. The
      extract reduced accumulation of radiolabelled dihydroartemisinin ((3)H-DHA) by
      erythrocytes infected with the chloroquine- and sulphonamide-resistant K1 strain
      of Plasmodium falciparum while it increased its accumulation by erythrocytes
      infected with the chloroquine-sensitive D10 strain. These results suggest complex
      interactions between the antimalarial medicinal plant and artemisinin. This study
      also proposes an in vitro approach to investigating interactions between
      antimalarial drugs and traditional medicines.

PMID- 16102930
TI  - Age-related changes in liver structure and function: Implications for disease ?
AB  - The geriatric populations of many countries are growing rapidly and they present
      major problems to healthcare infrastructures from both medical and economic
      perspectives. The elderly are predisposed to a variety of diseases, which
      contribute to a marked increase in morbidity in this subpopulation. The incidence
      of liver disease increases in the elderly, but the cellular and subcellular
      perturbations that underlie this suspected predisposition to pathology remain
      unresolved. Several age-related changes have been documented, including (a) a
      decline in liver volume, (b) an increase in the hepatic dense body compartment
      (lipofuscin), (c) moderate declines in the Phase I metabolism of certain drugs,
      (d) shifts in the expression of a variety of proteins and (e) diminished
      hepatobiliary functions. Other more subtle changes (e.g., muted responses to
      oxidative stress, reduced expression of growth regulatory genes, diminished rates
      of DNA repair, telomere shortening) may contribute to reduced hepatic
      regenerative capacity, shorter post-liver transplant survival and increased
      susceptibility to certain liver diseases in the elderly.

PMID- 16102931
TI  - Multivariate analysis of nystatin and metronidazole in a semi-solid matrix by
      means of diffuse reflectance NIR spectroscopy and PLS regression.
AB  - A multivariate method of analysis of nystatin and metronidazole in a semi-solid
      matrix, based on diffuse reflectance NIR measurements and partial least squares
      regression, is reported. The product, a vaginal cream used in the antifungal and
      antibacterial treatment, is usually, quantitatively analyzed through
      microbiological tests (nystatin) and HPLC technique (metronidazole), according to
      pharmacopeial procedures. However, near infrared spectroscopy has demonstrated to
      be a valuable tool for content determination, given the rapidity and scope of the
      method. In the present study, it was successfully applied in the prediction of
      nystatin (even in low concentrations, ca. 0.3-0.4%, w/w, which is around 100,000
      IU/5g) and metronidazole contents, as demonstrated by some figures of merit,
      namely linearity, precision (mean and repeatability) and accuracy.

PMID- 16102933
TI  - Objective and noninvasive detection of sub-clinical lung injury in breast cancer
      patients after radiotherapy.
AB  - AIMS: We employed technetium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO)
      lung scan to detect sub-clinical lung injury after radiation therapy of 60 female
      patients diagnosed with right breast cancer. METHODS: The degree of pulmonary
      vascular endothelium damage was represented as lung/liver uptake ratios (L/L
      ratios) calculated on Tc-99m HMPAO lung scan. All patients underwent simple
      mastectomy and post-operative radiotherapy of approximately 50 Gy. We divided the
      patients into three groups according to the interval between radiotherapy and
      lung Tc-99m HMPAO lung scan: Group 1 included 20 patients who received the lung
      scan within 1-3 months after radiotherapy, group 2 included 20 patients were
      within 3-9 months after radiotherapy, and group 3 included 20 patients were more
      than 9 months after radiotherapy. In addition, 20 age-matched normal women were
      included as the control group. RESULTS: The L/L ratios were 0.32+/-0.04 for
      normal controls, 0.59+/-0.10 for group 1, 0.55+/-0.07 for group 2, and 0.34+/
      0.04 for group 3, respectively. Based on our preliminary results, we found that
      sub-clinical lung injury and significantly increased L/L ratio in breast cancer
      patients received radiotherapy may occur within the first 6 months after
      radiotherapy. However, the L/L ratio is markedly decreased after 9 months.
      CONCLUSION: Our findings concluded that the degree of pulmonary vascular
      endothelium damage represented as the L/L ratio on Tc-99m HMPAO lung scan has the
      potential to be a sensitive, objective and noninvasive method to detect sub
      clinical lung injury in breast cancer patients received radiotherapy.

PMID- 16102934
TI  - Sulfiredoxin: a potential therapeutic agent?
AB  - The importance of antioxidants in maintaining homeostasis has long been accepted
      and includes antioxidant proteins such as, peroxiredoxin (Prx), superoxide
      dismutase and glutathione S transferases. Sulfiredoxin (Srx) is a recently
      identified antioxidant protein with a role in signaling through catalytic
      reduction of oxidative modifications. It was first characterized for its
      regulation of Prx(s) through reduction of the conserved cysteine from sulfinic to
      sulfenic acid, thereby impacting the role of Prx in regulation of downstream
      transcription factors and kinase signaling pathways. Furthermore, the reduction
      of sulfinic to sulfenic acid prevents further oxidation of the conserved cysteine
      residue to sulfonic acid, the end result of which is degradation. Srx also has a
      role in the reduction of glutathionylation a post-translational, oxidative
      modification that occurs on numerous proteins and has been implicated in a wide
      variety of pathologies, including Parkinson's disease. The regulation of
      glutathionylation/deglutathionylation (or thiol switch) has been likened to
      phosphorylation/dephosphorylation, another post-translational modification
      involved in the regulation of signaling pathways. Unlike, the reduction of Prx
      over-oxidation, Srx-dependent deglutathionylation appears to be non-specific.
      Deglutathionylation of multiple proteins has been observed both in vitro and in
      vivo in response to oxidative and/or nitrosative stress. This review discusses
      Srx as a novel antioxidant, and focuses on its potential role in the regulation
      of glutathionylation/deglutathionylation pathways, that have been implicated in a
      growing number of disease states.

PMID- 16102935
TI  - Gene expression profiling of mouse host response to Listeria monocytogenes
      infection.
AB  - The purpose of this study was to evaluate gene expression profiles in the liver
      and blood for prediction of infection severity from Listeria monocytogenes (LM).
      Mice were injected with medium broth (control) or a nonlethal or lethal dose of
      LM and sacrificed 6 h later. Gene expression changes were determined using
      Affymetrix MGU74Av2 GeneChips and confirmed by real-time polymerase chain
      reaction analysis. We identified discernable genes whose gene expression profiles
      can be used in pattern recognition to predict and classify samples in differently
      treated groups, with >or=90% accuracy in liver samples and 80% accuracy in blood
      at prediction; however, different genes were predictive in each tissue. Our
      results suggest that gene expression profiling in response to LM in mice may be
      able to distinguish samples in groups with varying severity of infection and
      provide information in finding molecular mechanisms and early biomarkers for
      subsequent conventional clinical endpoints.

PMID- 16102936
TI  - Acute stress exposure prior to influenza vaccination enhances antibody response
      in women.
AB  - Animal studies have shown that an acute stressor in close temporal proximity to
      immune challenge can enhance the response to delayed-type hypersensitivity and
      antibody response to vaccination. The current study examined the effects of acute
      exercise or mental stress prior to influenza vaccination on the subsequent
      antibody response to each of the three viral strains. Sixty young healthy adults
      (31 men, 29 women) were randomly allocated to one of three task conditions:
      dynamic exercise, mental stress, or control. After an initial baseline,
      participants completed their allocated 45 min task and then received the
      influenza vaccine. Plasma cortisol and interleukin-6 were determined at the end
      of baseline, after the task, and after 60 min recovery. Antibody titres were
      measured pre-vaccination and at 4 weeks and 20 weeks post-vaccination follow-ups.
      For the A/Panama strain, women in both the exercise and mental stress conditions
      showed higher antibody titres at both 4 and 20 weeks than those in the control
      condition, while men responded similarly in all conditions. Interleukin-6 at +60
      min recovery was found to be a significant predictor of subsequent A/Panama
      antibody response in women. In line with animal research, the current study
      provides preliminary evidence that acute stress can enhance the antibody response
      to vaccination in humans.

PMID- 16102937
TI  - Bottom-up and top-down signaling of IL-6 with and without habituation?

PMID- 16102938
TI  - Chronic biotoxin-associated illness: multiple-system symptoms, a vision deficit,
      and effective treatment.
AB  - Blooms of toxigenic organisms have increased in spatial and temporal extent due
      to human activities and natural forces that alter ecologic habitats and pollute
      the environment. In aquatic environments, harmful algal blooms pose a risk for
      human health, the viability of organisms, and the sustainability of ecosystems.
      The estuarine dinoflagellate, Pfiesteria piscicida, was discovered in the late
      1980s at North Carolina State University as a contaminant in fish cultures. P.
      piscicida was associated with fish death in laboratory aquaria, and illness among
      laboratory workers who inhaled the mist above aquaria. Both the fish and humans
      exhibited signs of toxicity. During the 1990s, large-scale mortality among fish
      and other aquatic organisms was associated with high concentrations of Pfiesteria
      sp. in estuaries on the eastern seaboard of North America from New York to Texas.
      Illness among humans was associated with direct exposure to estuaries and
      exposures to estuarine aerosols around the time of Pfiesteria-related fish kills.
      This review of the scientific literature on associations between Pfiesteria and
      human illness identified some of the possible mechanisms of action by which
      putative Pfiesteria toxins may have caused morbidity. Particular attention was
      given to the Pfiesteria-associated, human-illness syndrome known as Possible
      Estuary Associated Syndrome (PEAS). PEAS was characterized by multiple-system
      symptoms, deficits in neuropsychological tests of cognitive function, and rapid
      and severe decrements in visual contrast sensitivity (VCS), an indicator of
      neurologic function in the visual system. PEAS was diagnosed in acute and chronic
      illness cases, and was reacquired during re-exposure. Rapid normalization of PEAS
      signs and symptoms was achieved through the use of cholestyramine therapy.
      Cholestyramine, a non-absorbable polymer, has been used by humans to lower
      cholesterol levels since it was approved for that use by the U.S. Food and Drug
      Administration in 1958. When dissolved in water or juice and taken orally,
      cholestyramine binds with cholesterol, bile acids, and salts in the intestines,
      causing them to be eliminated rather than reabsorbed with bile during
      enterohepatic recirculation. Cholestyramine also has been reported to bind and
      eliminate a variety of toxic substances. The efficacy of cholestyramine therapy
      in treatment of PEAS supported the hypothesis that PEAS is a biotoxin-associated
      illness.

PMID- 16102939
TI  - On-chip visual perception of motion: a bio-inspired connectionist model on FPGA.
AB  - Visual motion provides useful information to understand the dynamics of a scene
      to allow intelligent systems interact with their environment. Motion computation
      is usually restricted by real time requirements that need the design and
      implementation of specific hardware architectures. In this paper, the design of
      hardware architecture for a bio-inspired neural model for motion estimation is
      presented. The motion estimation is based on a strongly localized bio-inspired
      connectionist model with a particular adaptation of spatio-temporal Gabor-like
      filtering. The architecture is constituted by three main modules that perform
      spatial, temporal, and excitatory-inhibitory connectionist processing. The
      biomimetic architecture is modeled, simulated and validated in VHDL. The
      synthesis results on a Field Programmable Gate Array (FPGA) device show the
      potential achievement of real-time performance at an affordable silicon area.

PMID- 16102940
TI  - Incremental learning of feature space and classifier for face recognition.
AB  - We have proposed a new approach to pattern recognition in which not only a
      classifier but also a feature space of input variables is learned incrementally.
      In this paper, an extended version of Incremental Principal Component Analysis
      (IPCA) and Resource Allocating Network with Long-Term Memory (RAN-LTM) are
      effectively combined to implement this idea. Since IPCA updates a feature space
      incrementally by rotating the eigen-axes and increasing the dimensions, the
      inputs of a neural classifier must also change in their values and the number of
      input variables. To solve this problem, we derive an approximation of the update
      formula for memory items, which correspond to representative training samples
      stored in the long-term memory of RAN-LTM. With these memory items, RAN-LTM is
      efficiently reconstructed and retrained to adapt to the evolution of the feature
      space. This function is incorporated into our face recognition system. In the
      experiments, the proposed incremental learning model is evaluated over a self
      compiled video clip of 24 persons. The experimental results show that the
      incremental learning of a feature space is very effective to enhance the
      generalization performance of a neural classifier in a realistic face recognition
      task.

PMID- 16102941
TI  - A new classifier based on information theoretic learning with unlabeled data.
AB  - Supervised learning is conventionally performed with pairwise input-output
      labeled data. After the training procedure, the adaptive system's weights are
      fixed while the testing procedure with unlabeled data is performed. Recently, in
      an attempt to improve classification performance unlabeled data has been
      exploited in the machine learning community. In this paper, we present an
      information theoretic learning (ITL) approach based on density divergence
      minimization to obtain an extended training algorithm using unlabeled data during
      the testing. The method uses a boosting-like algorithm with an ITL based cost
      function. Preliminary simulations suggest that the method has the potential to
      improve the performance of classifiers in the application phase.

PMID- 16102942
TI  - Olanzapine versus risperidone in the treatment of post-psychotic depression in
      schizophrenic patients.
AB  - OBJECTIVE: To compare the efficacy of two atypical antipsychotic drugs,
      olanzapine and risperidone, in schizophrenic patients with post-psychotic
      depression. RESULTS: A clinically significant decrease of MADRS scores occurred
      in patients treated with both drugs for 8 weeks. CONCLUSION: Atypical
      antipsychotic drugs may be particularly appropriate when treating schizophrenic
      patients with depression.

PMID- 16102943
TI  - Psychometric evaluation of the Readiness for Discharge Questionnaire.
AB  - OBJECTIVE: The Readiness for Discharge Questionnaire (RDQ) was developed as an
      easy to use tool for assessing readiness for discharge, independent of socio
      economic factors, for inpatients with schizophrenia. The psychometric properties
      of the RDQ are described. METHODS: The RDQ consists of 6 items assessing
      suicidality/homicidality, control of aggression/impulsivity, activities of daily
      living, medication-taking, delusions/hallucinations interfering with functioning
      and global status. A final yes/no question assesses readiness for discharge. Data
      derived from 3 studies (500 patients in 3 countries) were used in analyzing inter
      rater and test-retest reliability, content and construct validity, and
      sensitivity to change. RESULTS: The inter-rater reliability was high for all
      items of the RDQ (reliability coefficients >0.9) and moderate to high for the
      readiness for discharge status (Session I: 84% agreement, kappa 0.39, polychoric
      correlation r=0.81; Session II: 89% agreement, kappa 0.63, polychoric correlation
      r=0.81. Test-retest reliability was also high for all items of the RDQ
      (reliability coefficients >0.9) and the readiness for discharge status
      (kappa=0.743; tetrachoric correlation r=0.819). Overall, 84% of the raters agreed
      (mean score=5.0 of possible 6.0) that the RDQ was useful in assessing a patient's
      readiness for discharge from the hospital. Evidence of good construct validity
      included significant correlations with PANSS total and factor scores, and a
      significant relationship with actual discharge. Significantly more patients with
      symptom improvement were judged ready for discharge (compared to those without
      symptom improvement), indicating that the RDQ was sensitive to change over time.
      CONCLUSIONS: The RDQ has favorable reliability and validity properties, and is an
      easy to use instrument in research studies for assessing readiness for discharge
      of inpatients with schizophrenia. Additional work in naturalistic settings is
      required to further validate the instrument for routine clinical use.

PMID- 16102944
TI  - The effects of epigallocatechin-3-gallate on extracellular matrix metabolism.
AB  - BACKGROUND: Anti-oxidants have attracted a lot of interest on account of their
      function to protect the skin from oxidative stress by ultraviolet (UV) radiation.
      OBJECTIVE: This study examined the effects of epigallocatechin-3-gallate (EGCG),
      which is a green tea extract, on the extracellular matrix (ECM) changes induced
      by UV radiation and showed the comparative results with retinoic acid (RA).
      METHODS: The ECM metabolism is tightly controlled by the collagen degrading
      matrix metalloprotienases (MMPs) and their tissue inhibitors (TIMPs). Therefore,
      the expression of MMPs and TIMP-1 was investigated to evaluate the effects of
      EGCG and RA. Artificial skin was made using three-dimensionally cultured
      keratinocytes on a collagen matrix populated with fibroblasts. EGCG and RA were
      added into the medium of the fibroblasts and keratinocytes culture and also
      applied topically on artificial skins prior to UVA irradiation. The MMPs and TIMP
      1 expression levels were measured using Western blot and a zymogram. RESULTS:
      EGCG, like RA, decreased the level of MMPs production and increased TIMP-1
      expression level. However, EGCG suppressed the activities of the gelatinases and
      augmented the expressions of the TIMP-1 more than RA did. RA decreased the MMP-1
      and MMP-3 expression levels to a greater extent than EGCG. ECM alterations as a
      result of UVA appeared to be prevented more effectively using the EGCG treatment.
      CONCLUSION: EGCG can reverse the ECM degradation induced by UV even with a
      topical application of a practical-use concentration. In particular, EGCG proved
      to be much more effective in ROS-related conditions, such as UVA exposure.

PMID- 16102945
TI  - Versatility of the dipolar filter selection: from 1H nuclear spin diffusion
      experiment to the measurement of nuclear Overhauser effect in homopolymer melts.
AB  - Dipolar filters select 1H magnetization according to local dipolar dephasing,
      which corresponds to site mobility in systems with heterogeneous molecular
      mobility. Combined with a conventional exchange experiment, it is usually applied
      to polymeric samples exhibiting structures on the nanometer length scale
      associated with a strong dynamic contrast. There, the resulting 1H nuclear spin
      diffusion experiment yields the size of the structure. When the same experiment
      is applied to homopolymer melts exhibiting a weak dynamic contrast and dynamic
      heterogeneities on significant shorter length scales, the recorded magnetization
      decay is in agreement with decays expected from a heterogeneous nanostructure.
      However, dipolar filters actually can also select mobile parts of the repeat
      unit, e.g. the end of the alkyl side chains and the subsequent magnetization
      transfer then can occur via cross relaxation due to non coherent zero-quantum
      transitions (nuclear Overhauser effect, NOE). The difficulties of distinguishing
      these two cases are examined and it is demonstrated that NOE experiments
      exploiting magnetization selection via the dipolar filter allow quantifying the
      local dynamics of the side chains. This opens new possibilities for measurements
      of local dynamics in non isotopically labeled homopolymer melts.

PMID- 16102946
TI  - 129Xe NMR study of Xe adsorption on multiwall carbon nanotubes.
AB  - 129Xe NMR spectroscopy has been used to study the adsorption of Xe on multi-wall
      carbon nanotubes (MWCNT). The results obtained have shown the 129Xe NMR ability
      to probe the intercrystalline (aggregate) and the inner porosity of CNT. In
      particular, the effects on porosity of tubes openings by hydrogen exposure and of
      ball milling were examined. Dramatic changes observed in the 129Xe NMR spectra
      after moderate ball milling of MWCNTs were attributed to the destruction of the
      initial intercrystalline pore structure and to the Xe access inside the
      nanotubes. To examine the exchange dynamics the mixture of as-made and milled
      MWCNTs was studied with one- and two-dimensional (1D and 2D) 129Xe NMR. The
      exchange between the interior of milled nanotubes and the aggregate pores of as
      made MWCNTs was fast on the NMR acquisition time scale. The Xenon exchange
      between the interior of the as-made MWCNTs and the large aggregate pores occurred
      on a longer time scale of 10 ms, as was established by 2D 129Xe NMR exchange
      spectroscopy. Variable temperature 129Xe NMR data were also discussed and
      analyzed in terms of the fast exchange approximation.

PMID- 16102947
TI  - Changes of anti-oxidative enzymes and MDA content under soil water deficits among
      10 wheat (Triticum aestivum L.) genotypes at maturation stage.
AB  - Drought is a world-spread problem seriously influencing grain production and
      quality, the loss of which is the total for other natural disasters, with
      increasing global climate change making the situation more serious. Wheat is the
      staple food for more than 35% of world population, so wheat anti-drought
      physiology study is of importance to wheat production and biological breeding for
      the sake of coping with abiotic and biotic conditions. Much research is involved
      in this hot topic, but the pace of progress is not so large because of drought
      resistance being a multiple-gene-control quantitative character and wheat genome
      being larger (16,000Mb). On the other hand, stress adaptive mechanisms are quite
      different, with stress degree, time course, materials, soil quality status and
      experimental plots, thus increasing the complexity of the issue in question.
      Additionally, a little study is related to the whole life circle of wheat, which
      cannot provide a comprehensive understanding of its anti-drought machinery. We
      selected 10 kinds of wheat genotypes as materials, which have potential to be
      applied in practice, and measured change of relative physiological indices
      through wheat whole growing-developmental circle (i.e. seedling, tillering and
      maturing). Here, we reported the anti-oxidative results of maturation stage (the
      results of seedling and tillering stage have been published) in terms of
      activities of POD, SOD, CAT and MDA content as follows: (1) 10 wheat genotypes
      can be grouped into three kinds (A-C, respectively) according to their changing
      trend of the measured indices; (2) A group performed better resistance drought
      under the condition of treatment level 1 (appropriate level), whose activities of
      anti-oxidative enzymes (POD, SOD, CAT) were higher and MDA lower; (3) B group
      exhibited stronger anti-drought under treatment level 2 (light-stress level),
      whose activities of anti-oxidative enzymes were higher and MDA lower; (4) C group
      expressed anti-drought to some extent under treatment level 3 (serious-stress
      level), whose activities of anti-oxidative enzymes were stronger, MDA lower; (5)
      these results demonstrated that different wheat genotypes have different
      physiological mechanisms to adapt themselves to changing drought stress, whose
      molecular basis is discrete gene expression profiling (transcriptom); (6) our
      results also showed that the concept and method accepted and adopted by most
      researchers [T.C. Hsiao, Plant response to water stress, Ann. Rev. Plant Physiol.
      24 (1973) 519-570], that 75% FC is a proper supply for higher plants, was
      doubted, because this level could not reflect the true suitable level of
      different wheat genotypes. The study in this respect is the key to wheat anti
      drought and biological-saving water agriculture; (7) our research can provide
      insights into physiological mechanisms of crop anti-drought and direct practical
      materials for wheat anti-drought breeding; (8) the physiological study of wheat
      is more urgent up-to-date and molecular aspects are needed, but cannot substitute
      this important part. The combination of both is an important strategy and a key
      and (9) POD, SOD and CAT activities and MDA content of different wheat genotypes
      had quite different changing trend at different stages and under different soil
      water stress conditions, which was linked with their origin of cultivation and
      individual soil water threshold.

PMID- 16102949
TI  - The role of B cells and autoantibodies in rheumatoid arthritis.
AB  - In this article, we will review B lymphocyte development and function, then
      discuss the role of B cells in RA, including immune complex formation; the K/BxN
      mouse model of RA; toll-like receptors; B cells as antigen presenting cells;
      germinal center-like structures in RA synovium; and influence on T cell
      activation, leukocyte infiltration, and angiogenesis. With regard to autoantibody
      production, we will focus on rheumatoid factor (RF) and anti-CCP antibodies,
      particularly mechanisms of their production; sensitivity and specificity in RA;
      and their roles as prognostic factors. Other autoantibodies will be discussed, as
      will treatment implications and future areas of investigation related to B cells
      and autoantibodies in RA.

PMID- 16102948
TI  - Pharmacokinetic and pharmacodynamic modeling of recombinant human erythropoietin
      after multiple subcutaneous doses in healthy subjects.
AB  - A pharmacokinetic and pharmacodynamic (PK/PD) model for recombinant human
      erythropoietin (Epoetin alfa) in healthy subjects was developed to describe the
      time profiles of changes in serum Epoetin alfa and the pharmacological responses
      of percent reticulocytes, total red blood cell counts, and hemoglobin after
      single and multiple subcutaneous administration of Epoetin alfa. Data used in the
      development of the model were obtained from a clinical study carried out in
      healthy volunteers in which Epoetin alfa was administered either as 150 IU/kg
      three-times-a-week (t.i.w.) or fixed 40,000 IU weekly (q.w.) doses for 4 weeks. A
      dual-absorption rate model (fast zero-order and slow first-order inputs) with
      linear disposition kinetics was used to characterize the pharmacokinetics of
      erythropoietin after subcutaneous administration. A new catenary cell production
      and lifespan loss model was used to fit the pharmacodynamic data yielding
      estimates of SC50, Smax, and other pharmacodynamic parameters. Flip-flop kinetics
      was apparent in the pharmacokinetics as the absorption rate was slower (k(a) =
      0.7 day(-1)) than the elimination rate (CL/V(d) = 1.2-9.2 day(-1)). In the
      pharmacodynamics, an SC50 of 58 mIU/mL was estimated indicating that low serum
      erythropoietin concentrations were sufficient to produce pharmacological effects.
      The established PK/PD model predicts similar pharmacological responses of
      hemoglobin and total red blood cell counts for the 150 IU/kg t.i.w. and 40,000 IU
      q.w. regimens in healthy subjects.

PMID- 16102950
TI  - Effects of stress on exacerbation of diabetes mellitus, serum glucose and
      cortisol levels and body weight in rats.
AB  - OBJECTIVE: The effects of stress on the serum glucose, serum cortisol levels and
      body weight were investigated to clarify the possible link between the stress and
      diabetes. METHODS: The experiments were performed on nondiabetic and
      streptozotocin diabetic rats divided to control, sham and stressed groups. Water
      immersion was used as stressor. After the experiment, blood samples were
      collected. The serum glucose level (SGL) was measured by the glucose oxidase
      method and serum cortisol level (SCL) was determined by radioimmunoassay.
      RESULTS: Stress caused a significant increase in glucose level in both
      nondiabetic and diabetic rats. In diabetes rats, a significant increase in SCL
      was observed. Stress did not cause, however, significant increases in SCL. A
      significant weight loss took place in rats exposed to stress and that was much
      greater in diabetic animals. CONCLUSION: The stress with mainly psychic component
      exacerbated the diabetes in streptozotocin treated rats and the glucose levels
      increased significantly also in nondiabetic controls, but no glucose was detected
      in their urine.

PMID- 16102951
TI  - Teratogenic effects of retinoic acid on neurulation in mice embryos.
AB  - Retinoic acids (RA) are natural chemicals that exert a hormone-like activity and
      a variety of biological effects on early development of mouse. In this study, the
      probable teratogenic effects of RA on CNS have been investigated in pregnant mice
      (n = 20) divided into four groups: (1) untreated controls, (2) controls which
      received a single dose of DMSO, (3) a group that received 40 mg/kg, and (4) a
      group that received 60 mg/kg of all-trans RA in DMSO, respectively on the eighth
      day of gestation. Embryos whose dams had received 40 and 60 mg/kg doses of RA,
      showed malformations and decreased size. At 40 mg/kg dosage level, 50% of the
      embryos had closed neural tubes while at 60 mg/kg dosage level the neural tube
      failed to close. The neuroblast mantle layers were disorganized in the 40 mg/kg
      and even more in the 60 mg/kg exposed group compared to the controls. In mitosis,
      the density of chromatin was increased in the 60 mg/kg dose group. Compared to
      controls the 40 and 60 mg/kg dose groups of RA treated dams decreases in the
      luminal longitudinal and internal measures were observed. Also the thickness of
      ventricular, mantle and marginal layers was smaller. Wide intercellular spaces
      due to the degenerated cells at high doses of RA as well as an accumulation of
      intercellular fluid were observed. Therefore, the wedge shape of neuroepithelium
      was abolished, preventing the elevation of the neural wall.

PMID- 16102952
TI  - [Torsion of the spleen in children].
AB  - The wandering spleen is caused by congenital absence of fixating ligaments or
      abnormally long ligaments. It is an uncommon clinical entity, which rarely
      affects children. The clinical presentation of wandering spleen is variable, but
      the most dangerous complication is splenic torsion. A 7 year-old boy presented
      with abdominal pain and vomiting. The abdominal ultrasound scan discovered spleen
      ischemia. Volvulus of the spleen was evoked. Laparotomy was carried out and the
      patient underwent splenectomy. In this case the anatomical means of spleen fixity
      were absent. Because wandering spleen is uncommon in the paediatric population, a
      heightened awareness of the condition is required for accurate diagnosis and
      appropriate management. The treatment of choice is splenopexy, while if splenic
      necrosis is present, splenectomy is required.

PMID- 16102953
TI  - [Genetics contribution to the understanding of autism].
AB  - Autism is a pervasive developmental disorder characterised by an impairment in
      social interaction and in communication, with unusual behaviour. Genetic factors
      are predominent in autism pathogenesis, in contrast with the environmental
      factors that would modulate the phenotype. The genetic polymorphism and the
      phenotypic heterogeneity make the autism a complex disorder to study. Genetic
      research on families with multiple affected children and biochemical mechanisms
      studies represent the sources for identifying the susceptibility genes in autism.

PMID- 16102954
TI  - [Comparison of prescriptions by pediatricians and general practitioners: a
      population-based study in Franche-Comte from the database of Regional Health
      Insurance Fund].
AB  - OBJECTIVES: To compare the medical management of children by private
      pediatricians or by general practitioners. POPULATION AND METHODS: A
      retrospective cohort study analyzed information from the automated database of
      the Regional Health Insurance Fund for salaried workers in Franche-Comte from
      January 2001 through December 2002 and compared the mean rates of prescriptions
      in the populations seen only by general practitioners or mainly by pediatricians.
      RESULTS: Analysis concerned 1 535 208 visits (office and home). Management by
      pediatricians was associated with 25% fewer consultations and 6% fewer
      hospitalizations. Pediatricians also wrote 25% fewer prescriptions for drugs, 17%
      fewer for laboratory tests, and 42% fewer for speech and language therapy.
      Children seen by pediatricians took antibiotics much less often (penicillin: 
      24%; cephalosporins: -74%; macrolides: -53%) as well as half as many corticoids
      and NSAIDs. Their vaccination coverage was more complete (31% more hepatitis B
      vaccines, 7% more MMR), as was prevention against rickets and cavities (twice the
      rate of vitamin D and fluoride prescriptions). The population followed mainly by
      pediatricians included 25% more children with a chronic disease. CONCLUSION:
      General practitioners and pediatricians appear to differ significantly in their
      management of children. Other studies that can take into account such confounding
      factors as health status are needed to confirm these results.

PMID- 16102955
TI  - [A rare case of nasal and buccal obstruction in a child: the antrochoanal polyp
      of Killian].
AB  - Nasal obstruction is a frequent symptom of consultation in paediatric
      otorhinolaryngology. Usually, adenoid hypertrophy is the cause. Sometimes the
      examination reveals the presence of polyps in the nose. The antrochoanal polyp of
      Killian is particularly frequent in childhood. The obstruction is usually
      unilateral, but the posterior extension of a bulky polyp to the oropharynx can
      cause a major discomfort, sometimes a respiratory distress. We report the
      observation of a 10-year-old patient presenting a bulky polyp of Killian, visible
      in the oropharynx and then discuss the features of this polyp in the literature.

PMID- 16102956
TI  - The classification of cancer based on DNA microarray data that uses diverse
      ensemble genetic programming.
AB  - OBJECT: The classification of cancer based on gene expression data is one of the
      most important procedures in bioinformatics. In order to obtain highly accurate
      results, ensemble approaches have been applied when classifying DNA microarray
      data. Diversity is very important in these ensemble approaches, but it is
      difficult to apply conventional diversity measures when there are only a few
      training samples available. Key issues that need to be addressed under such
      circumstances are the development of a new ensemble approach that can enhance the
      successful classification of these datasets. MATERIALS AND METHODS: An effective
      ensemble approach that does use diversity in genetic programming is proposed.
      This diversity is measured by comparing the structure of the classification rules
      instead of output-based diversity estimating. RESULTS: Experiments performed on
      common gene expression datasets (such as lymphoma cancer dataset, lung cancer
      dataset and ovarian cancer dataset) demonstrate the performance of the proposed
      method in relation to the conventional approaches. CONCLUSION: Diversity measured
      by comparing the structure of the classification rules obtained by genetic
      programming is useful to improve the performance of the ensemble classifier.

PMID- 16102957
TI  - Low-level exposure to organophosphate pesticides leads to restrictive lung
      dysfunction.
AB  - Apart from symptomology, there are very few reports on lung function following
      exposure to low levels of organophosphate (OP) pesticides in man. Twenty-five
      occupationally exposed farmers and 22 environmentally exposed freshwater
      fishermen were evaluated between and during OP spray seasons. Forty marine
      fishermen living away from agricultural areas were recruited as a control group.
      Forced vital capacity (FVC) and forced expiratory volume in the first second
      (FEV(1)) were measured by spirometry. Haemoglobin corrected erythrocyte
      acetylcholinesterase (AChE) levels were measured during and between (baseline
      estimation) spray seasons using a portable WHO-approved Test-mate system (EQM
      Research, Ohio). FVC ratio was lower in the farmers as compared to the controls
      (P<0.001) between exposure seasons. In the farmers, FVC ratio decreased further
      during the exposure season (P=0.023). FEV(1) was lower in the farmers as compared
      to the controls in both periods (P<0.05). In the fishermen, the decrease in
      ratios of FVC and FEV(1) following exposure to pesticides was not significant.
      FEV(1)/FVC ratios were similar in the three groups between (P=0.988) and during
      (P=0.159) exposure periods. Following exposure to OPs, AChE levels dropped 12.75%
      in the farmers (P<0.001) and 5.62% in the freshwater fishermen (P=0.001).
      Occupational exposure to OP results in restrictive lung dysfunction, a phenomenon
      not observed following environmental exposure.

PMID- 16102958
TI  - Microbial strategies to target, cross or disrupt epithelia.
AB  - Epithelia are highly organized structures adapted to protect the underlying
      tissues from external aggressions, including microbial infections. Consequently,
      pathogens have evolved various strategies to target directly or indirectly
      intercellular junctions and/or components that maintain the structure of
      epithelia. Interestingly, some extracellular pathogens secrete enzymes that
      modify the extracellular part of junction components. Others produce toxins that
      are endocytosed and act from the inside of the cell to disrupt epithelial
      junctions. Other pathogens may directly inject into cells factors that are
      targeted to and destabilize the junctions, or that interact with signaling
      cascades that affect junction stability. Finally invasive bacteria or viruses
      may, by entering into cells, destabilize the junctions by targeting junction
      components directly or by inducing a series of events that lead to chemokine
      secretion, polymorphonuclear recruitment and inflammation.

PMID- 16102959
TI  - Dietary ratio of n-6/n-3 PUFAs and docosahexaenoic acid: actions on bone mineral
      and serum biomarkers in ovariectomized rats.
AB  - Hypoestrogenic states escalate bone loss in animals and humans. This study
      evaluated the effects of the amount and ratio of dietary n-6 and n-3
      polyunsaturated fatty acids (PUFAs) on bone mineral in 3-month-old sexually
      mature ovariectomized (OVX) Sprague-Dawley rats. For 12 weeks, the rats were fed
      either a high-PUFA (HP) or a low-PUFA (LP) diet with a ratio of n-6/n-3 PUFAs of
      5:1 (HP5 and LP5) or 10:1 (HP10 and LP10). All diets (modified AIN-93G) provided
      110.4 g/kg of fat from safflower oil and/or high-oleate safflower oil blended
      with n-3 PUFAs (DHASCO oil) as a source of docosahexaenoic acid (DHA). Fatty acid
      analyses confirmed that the dietary ratio of 5:1 significantly elevated the
      amount of DHA in the periosteum, marrow and cortical and trabecular bones of the
      femur. Dual-energy X-ray absorptiometry measurements for femur and tibia bone
      mineral content (BMC) and bone mineral density showed that the DHA-rich diets
      (HP5 and LP5) resulted in a significantly lower bone loss among the OVX rats at
      12 weeks. Rats fed the LP diets displayed the lowest overall serum concentrations
      of the bone resorption biomarkers pyridinoline (Pyd) and deoxypyridinoline,
      whereas the bone formation marker osteocalcin was lowest in the HP groups.
      Regardless of the dietary PUFA content, DHA in the 5:1 diets (HP5 and LP5)
      preserved rat femur BMC in the absence of estrogen. This study indicates that the
      dietary ratio of n-6/n-3 PUFAs (LP5 and HP5) and bone tissue concentration of
      total long-chain n-3 PUFAs (DHA) minimize femur bone loss as evidenced by a
      higher BMC in OVX rats. These findings show that dietary DHA lowers the ratio of
      18:2n-6 (linoleic acid)/n-3 in bone compartments and that this ratio in tissue
      correlates with reduced Pyd but higher bone alkaline phosphatase activity and BMC
      values that favor bone conservation in OVX rats.

PMID- 16102960
TI  - A micro-immuno supported liquid membrane assay (mu-ISLMA).
AB  - A chemiluminescent (CL) based micro-immuno supported liquid membrane assay (mu
      ISLMA) has been developed that enables clean up, enrichment and detection of
      simazine in a single miniaturised cartridge system. The mu-ISLM cartridge
      contains a supported liquid membrane (SLM) sandwiched between a donor and an
      acceptor plate (channel volumes 1.65 microL), the latter being covered by a thin
      layer of gold on to which anti-simazine antibodies were covalently immobilised
      via a self assembled monolayer (SAM) of either dithiobis(11-aminoundecane,
      hydrochloride) (DTAU) or beta-mercaptoethylamine (beta-MEA). The mu-ISLMA based
      on DTAU was characterised by both a high apparent extraction efficiency (E(app) =
      136%) and high apparent enrichment factor (E(e)(app) = 544), which resulted in a
      very high sensitivity for simazine (LOD = 0.1 ng L(-1)). The paper discusses the
      influence of the different SAMs and three different anti-simazine-antibody
      preparations (polyclonal, affinity purified polyclonal and monoclonal) on the
      extraction parameters and assay sensitivity. The influence of the sample matrix
      (e.g. mineral water, orange juice and milk) on the simazine mu-ISLMA was also
      investigated.

PMID- 16102961
TI  - Polydiacetylene (PDA)-based colorimetric detection of biotin-streptavidin
      interactions.
AB  - The natural binding of streptavidin (STA) for a small molecule, biotin, has made
      it a useful tool in specific targeting application, due to their most specific
      noncovalent biological interactions in nature. Here, we describe a
      polydiacetylene (PDA)-based colorimetric biosensor to detect the STA-biotin
      interactions. We synthesized two kinds of biotin-labeled 10,12-pentacosadiynoic
      acid (PCDA) monomers having 2(ethylene oxide) or 3(ethylene oxide) spacer and
      prepared biotin-modified PDA liposomes using them. Upon the addition of STA, the
      modified PDA liposomes showed a color change from blue to red in about 1h
      followed by their aggregation and precipitation. The aggregation was found to be
      due to the cross-linking between the PDA liposomes caused by the STA having four
      biotin binding sites, which was confirmed by their TEM analysis. Since the STA
      biotin interactions are widely adopted for various biological detection systems;
      the biotin-modified PDA sensor developed in this study has enormous potentials
      for the development of various colorimetric biosensors.

PMID- 16102963
TI  - HMG proteins: dynamic players in gene regulation and differentiation.
AB  - Core histones package the genome into nucleosomes and control its accessibility
      to transcription factors. High mobility group proteins (HMGs) are, after
      histones, the second most abundant chromatin proteins and exert global genomic
      functions in establishing active or inactive chromatin domains. It is becoming
      increasingly clear that they also specifically control the expression of a
      limited number of genes. Moreover, they contribute to the fine tuning of
      transcription in response to rapid environmental changes. They do so by
      interacting with nucleosomes, transcription factors, nucleosome-remodelling
      machines, and with histone H1.

PMID- 16102964
TI  - Preparation and properties of an immobilized pectinlyase for the treatment of
      fruit juices.
AB  - Pectinlyase, present in different commercial pectinases used in juice technology,
      was immobilized on alginate beads. The optimal conditions were: 0.17 g alginate
      ml(-1), 1.2% (w/v or v/v) enzyme concentration and acetic-HCl/glycine-HCl buffer
      at pH 3.6 or tris-HCl/imidazole buffer at pH 6.4. Maximum percentage of
      immobilization (10.6%) was obtained with Rapidase C80. Kinetic parameters of free
      and immobilized pectinlyase were also determined. The pH and temperature at which
      activity of soluble and immobilized enzyme was maximum were 7.2 and 55 degrees C.
      Thermal stability was not significantly altered by immobilization, especially at
      40 degrees C, showing two periods of different stability. Free and immobilized
      preparation reduced the viscosity of highly esterified pectin from 1.09 to 0.70
      and 0.72 mm(2) s(-1), respectively, after 30 min at 40 degrees C. Furthermore,
      the immobilized enzyme could be re-used through 4 cycles and the efficiency loss
      in viscosity reduction was found to be only 9.2%.

PMID- 16102965
TI  - A series of 5-(5,6)-dihydrouracil substituted 8-hydroxy-[1,6]naphthyridine-7
      carboxylic acid 4-fluorobenzylamide inhibitors of HIV-1 integrase and viral
      replication in cells.
AB  - Introduction of a 5,6-dihydrouracil functionality in the 5-position of N-(4
      fluorobenzyl)-8-hydroxy-[1,6]naphthyridine-7-carboxamide 1 led to a series of
      highly active HIV-1 integrase inhibitors. These compounds displayed low nanomolar
      activity in inhibiting both the strand transfer process of HIV-1 integrase and
      viral replication in cells. Compound 11 is a 150-fold more potent antiviral agent
      than 1, with a CIC(95) of 40 nM in the presence of human serum. It displays good
      pharmacokinetics when dosed in rats and dogs.

PMID- 16102966
TI  - Discovery of novel, potent, and orally active spiro-urea human glucagon receptor
      antagonists.
AB  - A novel class of spiro-ureas has been discovered as potent human glucagon
      receptor antagonists in both binding and functional assays. Preliminary studies
      have revealed that compound 15 is an orally active human glucagon receptor
      antagonist in a transgenic murine pharmacodynamic model at 10 and 30 mpk.
      Compound 15 is orally bioavailable in several preclinical species and shows
      selectivity toward cardiac ion channels and other family B receptors, such as
      hGIP1 and hGLP.

PMID- 16102967
TI  - Performance of the Faces Anxiety Scale in patients transferred from the ICU.
AB  - Intensive Care Unit (ICU) patients are often not able to respond to long self
      report instruments, therefore, in order to assess anxiety accurately, a short and
      easy to use measure is required. The Faces Anxiety Scale (FAS) developed by
      McKinley et al. [McKinley S, Coote K, Stein-Parbury J. Development and testing of
      a faces scale for the assessment of anxiety in critically ill patients. J Adv
      Nurs 2003;41(1):73-9.] has promised to be such an instrument. This study assessed
      the construct validity of the FAS against the well validated anxiety subscale of
      the Hospital Anxiety and Depression Scale (HADS), in an ICU population ready for
      transfer to the ward. The study was a part of a larger study of transfer anxiety.
      The FAS showed good correlation with the anxiety sub-scale of the HADS which
      strengthened over time. The FAS was easy and quick to use and seemed to measure
      anxiety in ICU patients that were ready to move to the wards, however, further
      testing in a larger sample and with sicker ICU patients is required.

PMID- 16102968
TI  - Critical care without walls: The role of the nurse consultant in critical care.
AB  - BACKGROUND: The nurse consultant role was first described in 1999 and has
      undergone little evaluation since. Critical care nurse consultant roles have
      developed against a background of service innovation following a review of adult
      critical care and have resulted in a variety of job roles and titles. There is
      some evidence to suggest that these posts are developing differentially and with
      varied role content. AIMS: To provide a profile of the nurse consultant in
      critical care. To identify critical care roles in practice. METHOD: A national
      postal survey of all 72 critical care nurse consultants in post in England by
      August 2003; response rate 72% (n = 52). RESULTS: The majority (54%) of critical
      care nurse consultants were aged between 40 and 50 years with a mean of 18.4
      years post registration experience. The majority held a higher degree (71%) and
      at least one additional professional qualification (96%); many (44%) continue to
      study. Most critical care nurse consultants (69%) reported that a nurse does not
      manage them operationally. Nurse consultants were taking the lead in developing
      care outside the traditional boundaries of the Intensive Care Unit (ICU) (mean
      involvement score, M = 4.25) and with outreach rounds on the wards (M = 3.78).
      Despite having an overall high involvement (M = 3.37) with the practice and
      service development function, they had a lower involvement with research
      activities (M = 2.87). They also had a low involvement with strategic
      organisations such as the Department of Health (M = 1.63), Strategic Health
      Authorities (M = 1.54) and Primary Care Trust's (M = 1.49). CONCLUSIONS: The
      critical care nurse consultants who responded to this survey were clinically
      experienced and educated to an advanced level. They were leading the care of
      critically ill patients outside the traditional boundaries of the ICU, but have
      significantly less involvement within the ICU. Nurse consultants' restricted
      involvement with strategic organisations may limit the development of the role.

PMID- 16102969
TI  - A 4pi(LS)beta-gamma coincidence system using a TDCR apparatus in the beta
      channel.
AB  - This article is an overview of the capabilities of a 4 pi(LS)beta-gamma
      coincidence counting system based on a liquid scintillation detector in the beta
      channel. Equipped with a three-photomultiplier apparatus designed for the triple
      to double coincidence ratio (TDCR) method, the 4 pi(LS)beta-gamma coincidence
      system developed at LNHB combines the two techniques. The 4 pi(LS)beta-gamma
      counting setup records the different types of scintillation events between
      photomultipliers (double and triple coincidences) and the associated gamma
      spectra according to a bi-dimensional configuration. When measuring the activity
      of a (54)Mn solution, the extrapolation method is carried out by defocusing the
      photomultipliers; this procedure allows the measurement of gamma-ray sensitivity
      of the scintillation cocktail in the 835 keV energy region. In addition, in the
      framework of a (65)Zn standardization, 4 pi(LS)beta-gamma measurements are
      compared with standard 4 pi(PC)beta-gamma anticoincidence counting using a
      proportional counter in the beta-channel.

PMID- 16102970
TI  - Endocannabinoids affect neurological and cognitive function in thioacetamide
      induced hepatic encephalopathy in mice.
AB  - Endocannabinoids function as neurotransmitters and neuromodulators in the central
      nervous system via specific receptors and apparently have a neuroprotective role.
      We assumed that the endocannabinoid system could be involved in the pathogenesis
      of hepatic encephalopathy (HE), a neuropsychiatric syndrome due to liver disease.
      We used a mouse model of a thioacetamide induced fulminant hepatic failure. We
      found that the levels of the endocannabinoid 2-arachidonoyl-glycerol (2-AG) were
      elevated in the brain. Treatment with either 2-AG or with the CB1 receptor
      antagonist, SR141716A, improved a neurological score, activity and cognitive
      function. Activation of the CB2 receptor by a selective agonist, HU308, also
      improved the neurological score. 2-AG activity could be blocked with the specific
      CB2 receptor antagonist SR144528A. The CB1 receptor agonist noladin ether was
      inactive. We conclude that the endocannabinoid system may play an important role
      in the pathogenesis of HE. Modulation of this system either by exogenous agonists
      specific for the CB2 receptors or possibly also by antagonists to the CB1
      receptors may have therapeutic potential.

PMID- 16102971
TI  - Cytokine gene expression in a murine wound healing model.
AB  - Inflammatory mediators have been shown to play a major role in the complex series
      of co-ordinated events that occur in wound healing responses following injury.
      However, to date most of the studies carried out have addressed the expression,
      interactions and role of only one or two cytokines that are thought to be
      involved in wound repair. This study has evaluated, in murine skin samples taken
      at 0, 3, 12, 18, 24, 48, 72, 120 and 168 h post-wounding, the expression of a
      wide range of cytokines with potential for a role in wound repair. Various
      techniques (reverse transcription polymerase chain reaction (RT-PCR), bioassays
      and ELISA) were used to evaluate cytokine expression in these samples at both the
      mRNA and protein expressions level. Semi-quantitative analysis using RT-PCR
      revealed that IL-1beta, IP10, bFGF, and TGFbeta3 up-regulated in wounded samples,
      compared to non-injured control samples. Expression of mRNA for other cytokines
      and inflammatory mediators, IL-1alpha, IL-6, TGFbeta1, TNFalpha, MIP-1alpha, MIP
      2, JE, KC, PDGFalpha and PDGFbeta, were found to be down-regulated in injured
      adult murine samples compared to normal control samples. Interestingly we failed
      to find evidence of mRNA expression for the cytokines IL-2, IL-4, IL-12, GM-CSF,
      IFNgamma and RANTES, in both non-injured and injured samples. These observations
      were also generally supported by the results obtained using bioassays for IL-1
      and IL-6 and ELISA for IL-1alpha, IL-1beta, IL-6, TNFalpha, and IFNgamma.

PMID- 16102972
TI  - Interleukin-7 administration alters intestinal intraepithelial lymphocyte
      phenotype and function in vivo.
AB  - BACKGROUND: Interleukin-7 (IL-7) plays a crucial role in controlling T-cell
      development and homeostasis. IL-7 knock out and IL-7 receptor knock out mice show
      distinct declines in absolute numbers of the intestinal intraepithelial
      lymphocytes (IEL). Therefore, we hypothesized that exogenous administration of IL
      7 would alter IEL phenotype and function. METHODS: Adult C57BL/6J mice were
      treated with IL-7 or saline. Mice were euthanized at day 7. Cytokine and
      keratinocyte growth factor (KGF) expressions were measured with RT-PCR. IEL
      phenotype was studied with flow cytometry. Finally, to address the association of
      endogenous epithelial cell (EC)-derived IL-7 and IEL, confocal microscopy was
      used to observe co-localization of IL-7 to IEL subpopulations. RESULTS: IL-7
      administration significantly increased IEL numbers. CD8alphabeta+ IEL increased
      3.2-fold, CD8+CD44+ IEL increased 1.3-fold, and alphabeta-T-cell receptor (TCR)+
      IEL increased 1.3-fold. IL-7 administration also significantly changed both
      alphabeta-TCR+ IEL- and gammadelta-TCR+ IEL-derived cytokine expressions.
      Interestingly, IL-7 administration also led to a significant increase in KGF
      expression. Confocal microscopy showed a high level of co-localization between
      the alphabeta-TCR+ IEL and EC-derived IL-7. gammadelta-TCR+ IEL showed a lower
      level, but still significant, co-localization. CONCLUSION: IL-7 administration
      significantly affected IEL phenotype and function. The observed co-localization
      suggests that there is a close IEL-EC cross-communication mediated by EC-derived
      IL-7 expression.

PMID- 16102973
TI  - Effect of 4-aminopyridine (4-AP) on the spontaneous activity and neuromuscular
      junction in the rat colon.
AB  - Two pacemakers are involved in the generation of the spontaneous electrical
      activity in the rat colon. Slow waves, originated near the submuscular plexus,
      elicit high frequency contractions whereas low frequency contractions are related
      to cyclic depolarizations, which might be originated near the Auerbach's plexus.
      Inhibitory junction potentials (IJPs) in the rat colon show a fast component
      followed by a sustained NO-mediated hyperpolarization. We have utilised
      mechanical recordings and intracellular electrophysiology to characterize the
      effects of 4-AP on spontaneous electrical activity and inhibitory
      neurotransmission in isolated preparations of rat colon. 4-AP reduced the
      repolarization of smooth muscle cells and caused a transient (for 4-5 min)
      depolarization (9.7 +/- 3.1 mV; n = 4) and repetitive spikes. The mechanical
      activity correlated with these electrical changes consisted of a transient
      increase in tone without cyclic activity followed by long lasting high amplitude
      cyclic contractions. To avoid smooth muscle cyclic depolarizations, nifedipine 1
      microM was added to the perfusion solution. 4-AP 5 mM hyperpolarized (-11.4 +/-
      2.1 mV, n = 5) the smooth muscle and induced spontaneous IJPs. This effect was
      not observed when the tissue was preincubated with TTX 1 microM (n = 7) and L-NNA
      1 mM (n = 4). We conclude that 4-AP inhibits repolarization of smooth muscle
      cells and induces release of NO from nerve endings. This effect might be due to
      inhibition of K(+) channels both in neurons and smooth muscle cells.

PMID- 16102974
TI  - Opsonic effect of congerin, a mucosal galectin of the Japanese conger, Conger
      myriaster (Brevoort).

PMID- 16102975
TI  - A flow cytometric approach to study intracellular-free Ca2+ in Crassostrea gigas
      haemocytes.
AB  - Bivalve haemocytes are essential in defence mechanisms including phagocytosis.
      They also produce molecules including hydrolytic enzymes and antimicrobial
      peptides that contribute to pathogen destruction. Although haemocyte activities
      have been extensively studied, relatively little is known about the intracellular
      signalling pathways that are evoked during haemocyte activation and especially
      the role of calcium. Flow cytometry has been used for the first time to define
      the effect of cell incubation in haemolymph and artificial sea water (ASW) on
      Pacific oyster, Crassostrea gigas, haemocytes. Cell viability, enzymatic
      activities (esterases and aminopeptidases), phagocytosis and granulocyte
      percentage were analysed. Viability and some activities were different in
      haemolymph and ASW. Cytoplasmic-free calcium in circulating haemocytes was then
      investigated by flow cytometry in both media using a calcium probe (Fluo-3/AM).
      To explore calcium homeostasis, different calcium modulators were tested. The
      calcium chelator Bapta/AM (10 microM) reduced significantly the percentage of
      Fluo-3-positive cells in ASW. In addition, ryanodine (5 microM) induced a
      significant enhancement of the percentage of Fluo-3 positive cells in haemolymph
      and in ASW. Flow cytometry may be used to study calcium movements in C. gigas
      haemocytes, but several haemocyte incubation media need to be tested in order to
      confirm results. The objective of the study should be considered before selecting
      a particular experimental medium.

PMID- 16102976
TI  - Innervation zone shift with changes in joint angle in the brachial biceps.
AB  - Empirical evidence is presented suggesting that the innervation zone of the
      brachial biceps shifts relative to recording electrodes with changes in joint
      angle. Myoelectric signal data were acquired from five subjects using a 16
      channel linear electrode array, and analyzed to determine a reversal in signal
      propagation direction indicating innervation zone location. An analysis of the
      effect of joint angle changes on innervation zone location yielded statistically
      significant results (ANOVA, alpha = 0.05, p < 0.001) suggesting that the
      innervation zone moves between 5 and 30 mm in a direction distal to the shoulder
      as the arm is extended, statistically independent of force level (ANOVA, alpha =
      0.05, p > 0.2).

PMID- 16102977
TI  - Precision of measurements of physical workload during standardised manual
      handling. Part II: Inclinometry of head, upper back, neck and upper arms.
AB  - For measuring the physical exposure/workload in studies of work-related
      musculoskeletal disorders, direct measurements are valuable. However, the between
      days and between-subjects variability, as well as the precision of the method per
      se, are not well known. In a laboratory, six women performed three standardised
      assembly tasks, all of them repeated on three different days. Triaxial
      inclinometers were applied to the head, upper back and upper arms. Between-days
      (within subjects) and between-subjects (within tasks) variance components were
      derived for the 10th, 50th and 90th percentiles of the angular and the angular
      velocity distributions, and for the proportion of time spent in predefined
      angular sectors. For percentiles of the angular distributions, the average
      between-days variability was 3.4 degrees , and the between-subjects variability
      4.0 degrees . For proportion of time spent in angular sectors, the variability
      depended on the percentage of time spent in the sector; the relative variability
      was scattered and large, on average 103% between days and 56% between subjects.
      For the angular velocity percentiles, the average between-days variability was
      7.9%, and the average between-subjects variability was 22%. The contribution of
      the measurement procedure per se to the between-days variability, i.e., the
      imprecision of the method, was small: less than 2 degrees for angles and 3% for
      angular velocity.

PMID- 16102978
TI  - Functional and EMG responses to a physical therapy treatment in patellofemoral
      syndrome patients.
AB  - There are several pathologies related to the patellofemoral joint, in which the
      patellofemoral syndrome is one of the most common and challenging to treat. The
      patellofemoral syndrome results from a malalignment of the knee extensor
      mechanism. The purpose of our study was to describe and compare EMG responses of
      the vastus medialis and vastus lateralis muscles while walking up and down stairs
      and other clinical and functional responses in PFS subjects before and after a
      physical therapy intervention. Eleven subjects were studied and divided in two
      groups: six subjects with clinically diagnosed patellofemoral syndrome and five
      healthy control subjects. Subjects were evaluated by a functional and
      biomechanical evaluation protocol: postural evaluation, pain and knee function
      evaluation, and electromyographic activity of vastus medialis and lateralis
      muscles while walking up and down a staircase. Results showed higher efficiency
      of the vastus medialis muscle in carrying out eccentric exercises and increased
      muscle activity in both the vastus medialis and vastus lateralis muscles while
      climbing stairs after physical therapy treatment. We were able to identify an
      improvement in postural alignment of lower limb muscles and knee functionality
      among patellofemoral syndrome group subjects after treatment.

PMID- 16102979
TI  - Task-dependent posterior cingulate activation in mild cognitive impairment.
AB  - Neuroimaging research has demonstrated that the posterior cingulate cortex (PCC)
      is functionally compromised in individuals diagnosed with amnestic mild cognitive
      impairment (MCI), a major risk factor for the development of Alzheimer's disease
      (AD). In functional MRI studies with healthy participants, this same region is
      active during self-appraisal (requiring retrieval of semantic knowledge about the
      self) as well as episodic recognition of previously learned information.
      Administering both types of tasks to people with MCI may reveal important
      information on the role of the PCC in recollection. This study investigated fMRI
      activation in the PCC in individuals with MCI and matched controls across two
      tasks. The first task was a visual episodic recognition task. The second task was
      an autobiographical self-appraisal task in which subjects rated themselves on a
      set of trait adjectives. Results of a conjunction analysis revealed the PCC as
      the sole region commonly active during both tasks in the healthy older adults.
      Furthermore, additional analysis revealed an interaction in the PCC, indicating a
      task-dependent response in the MCI group. MCI participants showed PCC activation
      during self-appraisal, but not episodic retrieval. This result suggests in MCI
      that the PCC shows functional degradation during episodic retrieval; however, the
      PCC's role in retrieval and evaluation of highly elaborated information regarding
      the self is more well-preserved.

PMID- 16102980
TI  - Integrated memory for objects, places, and temporal order: evidence for episodic
      like memory in mice.
AB  - Human episodic memory refers to the recollection of an unique past experience in
      terms of what happened, and where and when it happened. Factoring out the issue
      of conscious recollection, episodic memory, even at the behavioral level, has
      been difficult to demonstrate in non-human mammals. Although, it was previously
      shown that rodents can associate what and when or what and where information
      given on unique trials, it proved to be difficult to demonstrate memory for what,
      where, and when simultaneously in mammals, without using extensive training
      procedures, which might induce semantic rather than episodic memory recall.
      Towards the goal of an animal model of human episodic memory we designed an three
      trial object exploration task in which different versions of the novelty
      preference paradigm were combined to subsume (a) object recognition memory, (b)
      the memory for locations in which objects were explored, and (c) the temporal
      order memory for object presented at distinct time points. We found that mice
      spent more time exploring two "old familiar" objects relative to two "recent
      familiar" objects, reflecting memory for what and when and concomitantly directed
      more exploration at a spatially displaced "old familiar" object relative to a
      stationary "old familiar" object, reflecting memory for what and where. These
      results suggest that during a single test trial the mice were able to (a)
      recognize previously explored objects, (b) remember the location in which
      particular objects were previously encountered, and (c) to discriminate the
      relative recency in which different objects were presented. According to the
      currently discussed behavioral criteria for episodic-like memory in animals, our
      results suggest that mice are capable to form such higher order memories.

PMID- 16102981
TI  - Enhanced conditioning produced by surprising increases in reinforcer value are
      unaffected by lesions of the amygdala central nucleus.
AB  - In many experimental settings, lesions of the central nucleus of the amygdala
      (CN) interfere with surprise-induced enhancement of event processing. In those
      settings, surprise was produced by omitting an expected event. This experiment
      examined the effects of CN lesions on enhanced learning after surprise was
      induced by presenting an unexpected event. After extensive light-food pellet
      pairings, a light-noise compound was paired with food pellets, and a sucrose
      solution was unexpectedly delivered after the food. Relative to a control
      condition, this manipulation enhanced the formation of associations between the
      auditory conditioned stimulus and food, in both sham- and CN-lesioned rats. These
      results indicate that CN circuitry implicated in surprise-induced increases in
      event processing is preferentially engaged when expected events are omitted, and
      not when unexpected events are presented.

PMID- 16102982
TI  - A deformable model for automatic CT liver extraction.
AB  - RATIONALE AND OBJECTIVES: This study was performed to design an automatic liver
      region extraction system to facilitate clinical liver size estimation and further
      serve as a prestage for liver reconstruction and volume estimation. MATERIALS AND
      METHODS: We present a modification of the well-known snakes algorithm for
      extracting liver regions in noisy CT images. Our modification addresses the
      issues of selection of the control points on an estimate of the contour and the
      determination of the weighting coefficients. The weighting coefficients are
      determined dynamically on the basis of the distance between the control points
      and the local curvature of the contour. RESULTS: The proposed method was used in
      extracting liver regions from 98 cross-sectional abdominal images. The overall
      performance was estimated by comparisons with original liver regions. CONCLUSION:
      The deformable model method enables an efficient and effective automatic liver
      region extraction in noisy environments. This approach eliminates human-in-the
      loop, which is the common practice for the majority of current methods.

PMID- 16102983
TI  - Effects of dopexamine on lipid peroxidation during aortic surgery in pigs:
      comparison with dopamine.
AB  - OBJECTIVE: We investigated the dose-related effect of dopexamine and dopamine on
      free radical production and lipid peroxidation estimated by MDA measurements in
      an ischaemia-reperfusion model of supraceliac aortic repair. DESIGN: Prospective,
      randomized, blinded experimental study. MATERIALS: Twenty-five healthy pigs.
      METHODS: All experiments were performed under general endotracheal anaesthesia.
      Supraceliac aortic cross clamping was performed in all pigs. The pigs were
      randomly assigned into five groups (n=5 in each group) and received a continuous
      intravenous infusion of normal saline (CTL), dopamine 2 microg kg(-1)min(-1)
      (dopa 2), dopamine 8 microg kg(-1)min(-1) (dopa 8), dopexamine 2 microg kg(
      1)min(-1) (dopex 2), dopexamine 8 microg kg(-1)min(-1) (dopex 8). Cardiac output,
      mean arterial pressure, arterial blood gas analysis and blood sampling for plasma
      MDA measurements (to reveal lipid peroxidation) were recorded after induction of
      anaesthesia (baseline), 60 and 120 min after cross-clamping of aorta (ischaemia
      phase), and 60 and 120 min after restoration of flow (reperfusion phase).
      RESULTS: Dopexamine and dopamine at 8 microgkg(-1)min(-1) reduced MDA at 60 and
      120 min after reperfusion. CONCLUSION: Dopexamine seems superior to dopamine in
      reducing oxygen free radicals and subsequent lipid peroxidation during
      reperfusion after supraceliac aortic cross clamping in pigs.

PMID- 16102984
TI  - p40phox: the last NADPH oxidase subunit.
AB  - The phagocytic NADPH-oxidase is a multiprotein system activated during the
      inflammatory response to produce superoxide anion (O2-), which is the substrate
      for formation of additional reactive oxygen species (ROS). The importance of this
      system for innate immunity is established by chronic granulomatous disease (CGD),
      a primary immunodeficiency caused by defects in the NADPH oxidase. In this
      review, we present and discuss recent knowledge about p40phox, the last NADPH
      oxidase component to be identified. Furthermore, its interaction with cellular
      pathways outside of the NADPH oxidase is discussed. Described in this review is
      evidence that p40phox participates in NADPH oxidase dynamics within cells, what
      is known about its role in the oxidase, the possibility that p40phox participates
      in non-NADPH oxidase processes in phagocytic and non-phagocytic cells and whether
      p40phox could mediate a similar function in other NADPH oxidases. An improved
      understanding of p40phox should provide new insights about NADPH oxidase, the
      physiology of phagocytic cells and the innate immune system.

PMID- 16102985
TI  - Glucocerebrosidase recombinant allele: molecular evolution of the
      glucocerebrosidase gene and pseudogene in primates.
AB  - Glucocerebrosidase is a lysosomal enzyme that hydrolyses the beta-glycosidic
      linkage of glucocerebroside, a ubiquitous sphingolipid present in the plasma
      membrane of mammalian cells. Deleterious mutations in the glucocerebrosidase gene
      result in Gaucher disease, the most prevalent lysosomal storage disease. Humans
      have one glucocerebrosidase functional gene and pseudogene that were located 16
      kb apart on chromosome 1q21 and share 96% overall sequence similarity.
      Recombination between the two genes creates a 'complex allele' that renders
      glucocerebrosidase non-functional and accounts for >20% of the total Gaucher
      disease mutations in some population. The glucocerebrosidase pseudogene is absent
      in all other mammalian species surveyed so far. In order to learn more about the
      molecular evolution of the glucocerebrosidase functional gene and pseudogene, we
      have sequenced approximately 1.1 kb of the C-terminal region of these genes that
      encodes the enzyme catalytic site, from PCR-amplified genomic DNA of gorilla,
      chimpanzee, orangutan (the great apes), and squirrel monkey (a new-world monkey).
      In gorilla, chimpanzee, and orangutan, there are two copies of the
      glucocerebrosidase gene while the squirrel monkey possesses only a single copy.
      Similar to human, the second copy of glucocerebrosidase gene in gorilla and
      chimpanzee is non-functional because of a 55-bp deletion in exon 9, while that in
      orangutan appears to be unaffected and may still be functional. These data
      suggest that the glucocerebrosidase gene duplication event occurred after
      squirrel monkey divergence from the great apes, and that the exon 9 deletion that
      rendered the second copy of the glucocerebrosidase gene non-functional occurred
      prior to the divergence of gorilla and chimpanzee but after the divergence of
      orangutan from their common ancestor to human. The two genes in each species are
      least similar in gorilla and chimpanzee (97.8%) and most similar in orangutan
      (99.5%). None of the nucleotide variations in the GBA gene among the primates
      correspond to known mutations in Gaucher disease. Phylogenetic tree analysis
      using DNAstar and PAUP4.0 software indicates that gene conversion caused the
      evolution of glucocerebrosidase functional gene and pseudogene to be concerted.

PMID- 16102986
TI  - Cytokines and sleep.
AB  - Personal experience and empirical data indicate sleep is altered during sickness.
      Important signaling molecules of the peripheral immune system called cytokines
      orchestrate responses to infection. Through a variety of mechanisms, the brain
      detects activation of the peripheral immune system. The brain responds to
      infection by altering physiological processes and complex behavior, including
      sleep. These changes in physiology and behavior collectively function to support
      the immune system, and under normal circumstances the health of the host is
      restored. Several of these cytokines, and their receptors, are present in normal
      healthy brain. Some cytokines regulate sleep under physiological conditions, in
      the absence of infection or immune challenge. For example, interleukin-1 directly
      alters discharge patterns of neurons in hypothalamic and brainstem circuits
      implicated in the regulation of sleep-wake behavior. Many other cytokines
      modulate sleep because they interact with neurotransmitter, peptide, and/or
      hormone systems to initiate a cascade of responses that subsequently alter sleep
      wake behavior. Because cytokines regulate/modulate sleep-wake behavior in the
      absence of immune challenge, and cytokine concentrations and profiles are altered
      during infection, it is likely that cytokines mediate infection-induced
      alterations in sleep. Whether the changes in sleep that occur during infection
      are beneficial and aid in recovery remains to be determined.

PMID- 16102987
TI  - Effects of long term NOS inhibition on disease and the immune system in MOG
      induced EAE.
AB  - Hypothesising that systemically and intrathecally produced nitric oxide might
      play different roles in the EAE pathogenesis, we administered the NOS inhibitor N
      nitro-methyl-L-arginine-ester intrathecally or systemically via osmotic minipumps
      to DA rats with MOG induced EAE. We demonstrate an protective effect of the NOS
      inhibitor on EAE severity, the extent of CNS inflammation, and demyelination.
      Intrathecal administration was more effective when compared to systemic
      administration. The observed effect was accompanied by enhanced anti-MOG IgG1
      production. In our model, the therapeutic effect was concluded to be due to
      direct inhibition of the NO pathway in the CNS.

PMID- 16102988
TI  - Functional ability and muscle force in healthy children and ambulant Duchenne
      muscular dystrophy patients.
AB  - Neuromuscular disorders are characterised by progressive muscle weakness, which
      in time causes functional impairment. To quantify the extent of disease
      progression, muscle force and functional ability can be measured. Which of these
      parameters changes most depends on the disease stage. In a previous study, we
      reported normal values for muscle force obtained by hand-held dynamometry in
      healthy children aged 4-16 years. In the present study, we report normal values
      for timed functional tests in healthy children aged 4-11 years. These normal
      values were compared with values obtained in 16 ambulant patients with Duchenne
      muscular dystrophy (DMD) aged 5-8 years to study the extent of functional
      impairment. In ambulant patients with DMD, we found that muscle function assessed
      by timed functional tests (running 9 m and rising up from the floor) and muscle
      force assessed by hand-held dynamometry were severely impaired. However, a small
      reduction of muscle force was accompanied by a large reduction in functional
      ability. Therefore, in our group of ambulant patients with DMD, timed functional
      testing was the most sensitive parameter to determine the extent of disease
      progression. Timed functional testing may therefore be considered as an
      additional outcome measure in drug trials to evaluate the effects of therapy in
      ambulant patients with DMD and possibly in other neuromuscular disorders.

PMID- 16102989
TI  - Solid state 31P and 207Pb MAS NMR studies on polycrystalline O,O'
      dialkyldithiophosphate lead(II) complexes.
AB  - A number of lead(II) O,O'-dialkyldithiophosphate complexes were studied by (13)C,
      (31)P, and (207)Pb MAS NMR. Simulations of (31)P chemical shift anisotropy using
      spinning sideband analysis reveal a linear relationship between the SPS bond
      angle and the principal values delta(22) and delta(33) of the (31)P chemical
      shift tensor. The (31)P CSA data were used to assign ligands with different
      structural functions. In the cases of diethyldithiophosphate and di-iso
      butyldithiophosphate lead(II) complexes, (2)J((31)P, (207)Pb)-couplings were
      resolved and used to confirm the suggested assignment of the ligands. The SIMPSON
      computer program was used to calculate (31)P and (207)Pb spectral sideband
      patterns.

PMID- 16102990
TI  - Membrane protein structure quality in molecular dynamics simulation.
AB  - Our goal was to assess the relationship between membrane protein quality, output
      from protein quality checkers and output from molecular dynamics (MD)
      simulations. Membrane transport proteins are essential for a wide range of
      cellular processes. Structural features of integral membrane proteins are still
      under-explored due to experimental limitations in structure determination.
      Computational techniques can be used to exploit biochemical and medium resolution
      structural data, as well as sequence homology to known structures, and enable us
      to explore the structure-function relationships in several transmembrane
      proteins. The quality of the models produced is vitally important to obtain
      reliable predictions. An examination of the relationship between model stability
      in molecular dynamics (MD) simulations derived from RMSD (root mean squared
      deviation) and structure quality assessment from various protein quality checkers
      was undertaken. The results were compared to membrane protein structures, solved
      at various resolution, by either X-ray or electron diffraction techniques. The
      checking programs could predict the potential success of MD in making functional
      conclusions. MD stability was shown to be a good indicator for the quality of
      structures. The quality was also shown to be dependent on the resolution at which
      the structures were determined.

PMID- 16102991
TI  - Proteases in egg, miracidium and adult of Fasciola gigantica. Characterization of
      serine and cysteine proteases from adult.
AB  - Proteolytic activity of 0-12 day old eggs, miracidium and adult worm of Fasciola
      gigantica was assessed and proteases were partially purified by DEAE-Sepharose
      and CM-cellulose columns. Four forms of protease were separated, PIa, PIb, PIc
      and PII. Purifications were completed for PIc and PII using Sephacryl S-200
      chromatography. A number of natural and synthetic proteins were tested as
      substrates for F. gigantica PIc and PII. The two proteases had moderate activity
      levels toward azoalbumin and casein compared to azocasein, while gelatin,
      hemoglobin, albumin and fibrin had very low affinity toward the two enzymes.
      Amidolytic substrates are more specific to protease activity. PIc had higher
      affinity toward BAPNA-HCl (N-benzoyl-arginine-p-nitroanilide-HCl) and BTPNA-HCl
      (N-benzoyl-tyrosine-p-nitroanilide-HCl) at pH 8.0 indicating that the enzyme was
      a serine protease. However, PII had higher affinity toward BAPNA at pH 6.5 in the
      presence of sulfhydryl groups (beta-mercaptoethanol) indicating that the enzyme
      was a cysteine protease. The effect of specific protease inhibitors on these
      enzymes was studied. The results confirmed that proteases PIc and PII could be
      serine and cysteine proteases, respectively. The molecular weights of F.
      gigantica PIc and PII were 60,000 and 25,000, respectively. F. gigantica PIc and
      PII had pH optima at 7.5 and 5.5 and K(M) of 2 and 5 mg azocasein/mL,
      respectively. For amidolytic substrates, PIc had K(M) of 0.3 mM BAPNA/mL and 0.5
      mM BTPNA/mL at pH 8.0 and PII had K(M) of 0.6 mM BAPNA/mL at pH 6.5 with reducing
      agent. F. gigantica PIc and PII had the same optimum temperature at 50 degrees C
      and were stable up to 40 degrees C. All examined metal cations tested had
      inhibitory effects toward the two enzymes. From substrate specificity and
      protease inhibitor studies, PIc and PII could be designated as serine PIc and
      cysteine PII, respectively.

PMID- 16102992
TI  - Association between birth weight, body mass index and IGF2/ApaI polymorphism.
AB  - Insulin-like growth factor II (IGF-II) is a polypeptide that plays a key role in
      mammalian growth, influencing fetal cell division, differentiation, and possibly
      metabolic regulation. In adult humans, polymorphisms of the IGF2 gene have been
      associated with predisposition to obesity. In the present study, we tested the
      association between IGF2/ApaI genotype and Body Mass Index (BMI) in 294 healthy
      volunteers (95 men and 199 women; 18-30y) and correlated the results with their
      birth weights (BW) in order to investigate the relationship between this
      polymorphic site, fetal life and adult BMI. Blood samples were obtained for DNA
      extraction, PCR and genotyping. The statistical analyses were performed by the
      Chi-square, Kolmogorov-Smirnov normality, and Tukey post hoc tests. Although the
      IGF2 genotype was not significantly associated with BMI and/or BW, we observed a
      statistically significant correlation of 0.33 (p < 0.023) between BW and BMI in
      GG subjects whose BW was higher than 3.5 kg (n = 47). We hypothesize that high
      BWs associated with homozygosis for the G allele of IGF2/ApaI is not a null
      factor and might be associated with predisposition to high BMI in young adults.

PMID- 16102993
TI  - Detailed design and comparative analysis of protocols for optimized production of
      high-performance HIV-1-derived lentiviral particles.
AB  - Transgenic HIV-1-derived lentiviral particles are at the forefront of current
      gene therapy and tissue engineering initiatives, which will require optimal
      protocols for large-scale production of clinical-grade therapeutic lentiviruses.
      Production of latest-generation self-inactivating lentiviral particles requires
      cotransfection of mammalian production cell lines with two helper plasmids along
      with the lentivector, whose transgene-encoding expression cassette is the only
      genetic information stably transduced into target chromosomes. Capitalizing on a
      recently designed lentiviral expression vector family, we conducted rigorous
      analysis of production-relevant parameters including transfection, cell density,
      media composition, temperature, relative (helper) vector concentrations and
      genetic configuration. Comparative analysis of lentiviral particle performance
      (VP) was based on the viral titer (reflecting the number of transduction
      competent lentiviral particles) relative to the number of lentiviral particles
      produced (correlating with p24 production levels) (VP=titer/viral particle
      number). Optimal lentiviral production parameters, resulting in up to 132-fold
      greater VP compared to standard protocols, required (i) CaPO4-based transfection
      (ii) of helper plasmids and lentivector at a fixed concentration ratio (helper
      plasmid I:helper plasmid II:lentivector=1:1:2) (iii) into 1x10(5) human embryonic
      kidney cells/cm2 (HEK293-T) (iv) cultivated at 37 degrees C (v) in Advanced D-MEM
      medium supplemented with (vi) 2% fetal calf serum, (vii) and a culture additive
      containing 0.01 mM cholesterol, 0.01 mM egg's lecithin and 1x chemically defined
      lipid concentrate. (viii) Furthermore, constitutive transgene expression units
      placed in a forward polyadenylation site (pA)-free orientation relative to the
      lentivector backbone resulted in optimal transgene transduction/expression. Our
      studies suggest that detailed knowledge of lentivector design and the production
      of lentiviral particles will advance large-scale manufacturing of clinically
      relevant lentiviruses for future gene therapy applications.

PMID- 16102994
TI  - Regulation of human erythrocyte metabolism by insulin: cellular distribution of 6
      phosphofructo-1-kinase and its implication for red blood cell function.
AB  - Human erythrocytes are highly specialized cells whose function is oxygen
      transport. These cells' sole metabolic source of energy is the fermentation of
      glucose via glycolysis. They contain an active insulin receptor and respond to
      insulin by increasing phosphorylation of tyrosine residues in several proteins.
      However, no metabolic effects have yet been associated with activation of this
      receptor in human erythrocytes. Here, we show that insulin increases the rate of
      glycolysis in human erythrocytes. Lactate production increased 56 and 173% in the
      presence of 10 and 100 nM insulin, respectively. A higher insulin concentration
      (1000 nM) partially reversed the stimulation of glycolysis. These effects occur
      through activation of the key glycolytic enzyme 6-phosphofructo-1-kinase, which
      exhibits the same pattern of modulation by insulin as seen for glycolytic flux.
      This modulation also occurs physiologically since ex vivo experiments revealed
      50% stimulation of 6-phosphofructo-1-kinase (PFK) activity following a high
      carbohydrate meal. Insulin increases phosphorylation of PFK and redistributes the
      enzyme in red blood cells, causing it to detach from the erythrocyte membrane:
      upon insulin stimulation, the amount of enzyme associated with the plasma
      decreases by 86%. Detachment is a common mechanism of enzyme activation. As a
      consequence, insulin prevents up to 68% of red cells hemolysis. These results
      show that insulin regulates erythrocyte glycolysis and viability and suggest that
      this regulation is associated to other erythrocyte functions such as oxygen
      transport. Finally, we suggest that this regulatory mechanism might be
      compromised in patients with diabetes mellitus.

PMID- 16102996
TI  - Mechanisms causing effects of muscle position on proximo-distal muscle force
      differences in extra-muscular myofascial force transmission.
AB  - Certain recent studies showed that extra-muscular myofascial force transmission
      affects the length-force characteristics of rat extensor digitorium longus (EDL)
      muscle significantly after distal or proximal lengthening. This suggested that
      the relative position of a muscle with respect to its surrounding connective
      tissues is a co-determinant of muscle force in addition to muscle length, and
      indicated major effects on muscular mechanics. The specific goal of the present
      study is to investigate such effects by studying: (1) distributions of lengths of
      sarcomeres within muscle fibres and (2) the relative contributions of muscle
      fibres and the extra-cellular matrix to muscle total force, using a finite
      element model. The length of the muscle modelled was kept constant at a high and
      at a low muscle length whereas the relative position of the muscle was altered
      exclusively. For both muscle lengths, the forces exerted at distal and proximal
      tendons were unequal at almost all muscle relative positions. The proximo-distal
      force difference was enhanced as the muscle was repositioned away from its
      reference position. This confirmed the role of relative position of a muscle as a
      co-determinant of muscle force. At higher muscle lengths, distributions of
      lengths of sarcomeres arranged in series within muscle fibres were substantial.
      The force transmitted by the muscles' extra-cellular matrix comprised a sizable
      part of muscle total force. At lower muscle lengths distribution of sarcomere
      lengths was relatively limited indicating that the extra-cellular matrix is
      bearing the extra-muscular force. However, minor sarcomere length changes were
      shown to accumulate to sizable effects on the summed forces exerted by the muscle
      fibres. In addition, the extra-muscular load was shown to manipulate the force
      exerted by the extra-cellular matrix. We conclude that the relative position of a
      muscle has substantial effects on intra-muscular mechanics and the importance of
      the role of the extra-cellular matrix in determining the proximo-distal force
      differences is comparable to that of the intra-cellular domain.

PMID- 16102997
TI  - Non-motor manifestations in essential tremor: use of a validated instrument to
      evaluate a wide spectrum of symptoms.
AB  - INTRODUCTION: Recent studies suggest an association between non-motor symptoms
      and essential tremor (ET). Few studies have assessed psychological symptoms in
      ET. These studies were limited to western white populations and utilized scales
      that were specific to only one or two psychiatric domains. By contrast, the
      Symptom Checklist-90R (SCL-90R) is a validated clinical scale to screen for
      symptoms related to a spectrum of nine different psychological domains.
      OBJECTIVE: To determine whether a wide spectrum of non-motor manifestations is
      associated with ET in patients in an Asian cohort. METHODS: Consecutive ET
      patients and a group of control subjects were evaluated using the SCL-90R, which
      is comprised of items in nine major symptom dimensions and three global indices,
      including the positive symptom distress index. RESULTS: ET patients (N = 84) and
      controls (N = 78) were similar in age (50.0+/-18.0 vs 46.0+/-14.4 years), gender
      and other demographic variables. ET patients had higher scores in three of nine
      major symptom dimensions: anxiety, phobic anxiety (p < 0.0005) and psychoticism
      (p = 0.005). In multivariate analysis, the anxiety (p < 0.0005) and the positive
      symptom distress index scores (p < 0.0005) were greater in ET patients compared
      to controls after adjusting for sex, age, marital status and educational level.
      The severity, but not duration of ET was correlated with the severity of anxiety
      symptoms. CONCLUSIONS: Utilizing the SCL-90R, we highlighted that ET patients
      reported more non-motor symptoms than healthy controls. The more frequent
      occurrence of anxiety symptoms in our Asian cohort extends the observation that
      such non-motor manifestations should be considered in the clinical management of
      ET.

PMID- 16102998
TI  - Essential tremor: mild olfactory dysfunction in a cerebellar disorder.
AB  - Olfactory dysfunction has been reported to occur in patients with cerebellar
      disorders, including degenerative ataxias and essential tremor (ET). Previous
      studies have not considered the effects of mild cognitive deficits, which can
      occur in ET, and could explain the lower olfaction test scores in ET cases. We
      more than doubled our initial sample (37 ET cases and 37 controls) [Louis ED,
      Bromley SM, Jurewicz EC, Watner D. Olfactory dysfunction in essential tremor: a
      deficit unrelated to disease duration or severity. Neurology 2002;59:1631-3. ]
      and made adjustments for the mini mental status test score. The University of
      Pennsylvania Smell Identification Test score remained lower in 87 ET cases
      compared to 92 controls after adjustment for mini mental status test score and
      other potential confounders (p = 0.04). These findings: suggest that olfactory
      dysfunction in ET patients occurs independently of mild cognitive deficits and
      support recent work that the cerebellum may play a role in central olfactory
      processing.

PMID- 16102999
TI  - Clinical traits of LRRK2-associated Parkinson's disease in Ireland: a link
      between familial and idiopathic PD.
AB  - The role of genetics in parkinsonism has been confirmed over the last decade with
      the identification of genetic variation in seven genes, which are causative in
      familial forms of the disorder. A number of pathogenic mutations have been
      identified in the latest gene LRRK2, with a Gly2019Ser amino acid substitution
      identified in two siblings and one patient with idiopathic Parkinson's disease
      from Ireland. The clinical features resemble the idiopathic variant with a tremor
      predominant clinical picture shared by the siblings, slow progression of
      symptoms, and no observation of cognitive disturbance in all. The family and the
      sporadic individual were apparently not related and originated from different
      regions of Ireland, although haplotype analysis does suggest they share a common
      founder. The influence of the G2019S substitution on protein function and disease
      phenotype has yet to be fully resolved, but its elucidation will undoubtedly
      further our understanding of the mechanisms underlying Parkinson's disease.

PMID- 16103000
TI  - Quality of life in Essential Tremor Questionnaire (QUEST): development and
      initial validation.
AB  - BACKGROUND/OBJECTIVE: Essential tremor (ET) can diminish functioning and quality
      of life (QOL) but generic QOL measures may be relatively insensitive to ET and
      its therapies. We sought to develop an ET-specific measure that might be more
      sensitive, acceptable to patients, relatively brief, and easily used.
      DESIGN/METHODS: A sample of 200 patients (average age 70 years, range 30-91;
      average disease duration 15 years) rated the extent to which tremor impacts a
      function or state, tremor severity in various body parts, perceived health, and
      overall QOL. Responses to this initial questionnaire were subjected to principal
      components analysis (PCA). Inspection of factor coordinates, Eigenvalues,
      variance accounted for, and correlation matrices were used to select items for
      confirmatory PCA. Final scale reliability was assessed using Cronbach's alpha.
      Validity was evaluated by correlations between QOL scales and self-rated tremor
      severity. RESULTS: PCA of 65 initial items yielded 11 factors accounting for 71%
      of variance. Six factors were discarded. Two items were eliminated for not
      loading on a factor and 33 for perceived redundancy. Confirmatory PCA of the
      retained 30 items yielded an almost identical factor structure (six factors, 70%
      of variance accounted for, and similar item loadings). Because two factors had
      very few items loading on them, these two factors were combined into one scale.
      The final measure has five scales: Physical, Psychosocial, Communication,
      Hobbies/Leisure, and Work/Finance. Reliability was excellent for the whole
      instrument and four scales (> or =0.89), and good for the Work/Finance scale
      (0.79). Severity of voice and head tremor were the best correlates of
      Communication (0.70 and 0.35), while the Physical scale was related to right and
      left upper extremity tremor (0.59 and 0.56). Scales correlated more highly with
      patients' rating of their overall QOL than their health perception. CONCLUSIONS:
      A brief, 30-item, ET-specific QOL scale with excellent reliability was developed.
      Preliminary validity data are encouraging. The Quality of Life in Essential
      Tremor Questionnaire (QUEST) promises to facilitate QOL measurement in ET.

PMID- 16103001
TI  - The Lewis family revisited: no evidence for autosomal dominant multiple system
      atrophy.
AB  - In 1964, Lewis reported a familial ataxia-dysautonomia syndrome reminiscent of
      Shy-Drager syndrome subsequently known as multiple system atrophy (MSA). Here we
      review this report and propose that the Lewis family may represent an unusual
      form of autosomal dominant cerebellar ataxia type I, which might be categorized
      either as SCA3 (Machado-Joseph disease) or a new SCA subtype. There remains no
      conclusive evidence to support the notion of hereditary MSA.

PMID- 16103002
TI  - Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and
      organism.
AB  - The recent knowledge on mitochondria as the substantial source of reactive oxygen
      species, namely superoxide and hydrogen peroxide efflux from mitochondria, is
      reviewed, as well as nitric oxide and subsequent peroxynitrite generation in
      mitochondria and their effects. The reactive oxygen species formation in
      extramitochondrial locations, in peroxisomes, by cytochrome P450, and NADPH
      oxidase reaction, is also briefly discussed. Conditions are pointed out under
      which mitochondria represent the major ROS source for the cell: higher percentage
      of non-phosphorylating and coupled mitochondria, in vivo oxygen levels leading to
      increased intensity of the reverse electron transport in the respiratory chain,
      and nitric oxide effects on the redox state of cytochromes. We formulate
      hypotheses on the crucial role of ROS generated in mitochondria for the whole
      cell and organism, in concert with extramitochondrial ROS and antioxidant
      defense. We hypothesize that a sudden decline of mitochondrial ROS production
      converts cells or their microenvironment into a "ROS sink" represented by the
      instantly released excessive capacity of ROS-detoxification mechanisms. A partial
      but immediate decline of mitochondrial ROS production may be triggered by
      activation of mitochondrial uncoupling, specifically by activation of recruited
      or constitutively present uncoupling proteins such as UCP2, which may
      counterbalance the mild oxidative stress.

PMID- 16103003
TI  - Reduced mitochondrial formation of H(2)O(2) is responsible for resistance of
      dimethyl sulfoxide differentiated U937 cells to peroxynitrite.
AB  - Previous studies performed in our laboratory indicated that non-toxic
      concentrations of peroxynitrite nevertheless commit U937 cells to a rapid
      necrosis that is however prevented by a survival signaling driven by cytosolic
      phospholipase A(2)-released arachidonic acid. Toxicity was mediated by
      concentrations of peroxynitrite resulting in H(2)O(2)-dependent inhibition of
      arachidonic acid release. The present study shows that U937 cells differentiated
      to monocytes by prolonged exposure to dimethyl sulfoxide are resistant to
      peroxynitrite because able to respond with enhanced release of arachidonic acid.
      An additional important observation was that these cells require more
      arachidonate than the undifferentiated cells to support the survival signaling.
      The enhanced arachidonic acid release was not associated with changes in
      cytosolic phospholipase A(2) expression but was rather dependent on the increased
      responsiveness of the enzyme to calcium-dependent stimulation as well as on
      reduced mitochondrial formation of H(2)O(2). The latter event was found to be
      critical, since differentiated and undifferentiated cells were equally sensitive
      to peroxynitrite when the accumulation of H(2)O(2) was enhanced via depletion of
      catalase, or addition of a complex III inhibitor. Thus, the strategy selected by
      the differentiation process to allow monocytes to cope with peroxynitrite appears
      to involve some specific mechanism preventing the mitochondrial formation of
      H(2)O(2).

PMID- 16103004
TI  - Mouse models created to study the pathophysiology of Type 2 diabetes.
AB  - Obesity and Type 2 diabetes have become epidemics in the Western world.
      Understanding the pathophysiology of the disease should help in prevention and
      treatment of these disorders. A common theme is the presence of insulin
      resistance that eventually results in Type 2 diabetes. To understand the
      underlying mechanisms in the progression of the disease states, investigators
      have created mouse models by transgenic overexpression of a candidate gene or
      produced gene-deletion mouse models. This review will summarize many of the more
      appropriate models that study insulin resistance and Type 2 diabetes.

PMID- 16103005
TI  - Differential effects of diethylcarbamazine, tetracycline and the combination on
      Brugia pahangi adult females in vitro.
AB  - Anti-filarial effects of diethylcarbamazine (DEC), tetracycline (TC) and the
      combination on Brugia pahangi adult females were studied in 7-day cell-free
      culture, in terms of microfilaria release, parasite motility, MTT assay for
      parasite viability and embryogram. TC 50 microg/ml (TC50) effectively reduced
      microfilaria release from day 1 of culture. Combined with DEC 100 microg/ml
      (DEC100) or DEC 500 microg/ml (DEC500), microfilaria release reduced further and
      synergistically. TC50 also reduced motility, but DEC100 and DEC500 did not. The
      combination of TC50 and DEC500 reduced motility synergistically. The MTT assay
      supported the results of motility study in general. The embryogram showed that
      only DEC500 reduced the total number of intrauterine embryos, especially ova,
      indicating that DEC500 inhibited early embryogenesis. TC50 did not affect the
      total number of embryos, but resulted in apparent accumulation of microfilariae
      in the uterus, suggesting that the drug inhibited release of microfilariae in
      this in vitro system. These results clarified different anti-female mechanisms
      between DEC and TC. A PCR-based study showed that endosymbiont bacteria,
      Wolbachia, in B. pahangi females decreased significantly after TC treatment.
      However, this study could not determine whether the effects of TC were direct or
      Wolbachia-mediated.

PMID- 16103006
TI  - EPR parameters and local geometry for Cr3+ and V2+ ions in HfS2 crystals.
AB  - From the high-order perturbation formulas of EPR parameters (zero-field splitting
      D, g factors gparallel, gperpendicular and hyperfine structure constants
      Aparallel, Aperpendicular) based on the two spin-orbit coupling parameter model
      for 3d3 ions in trigonal symmetry, the EPR parameters of Cr3+ and V2+ ions in
      HfS2 crystals are calculated. From the calculations, it is found that the local
      trigonal distortion angle theta of impurity center in HfS2:Cr3+ is smaller than
      that in HfS2:V2+. The dominant cause of the small zero-field splitting |D| and g
      anisotropy |Deltag|=|gparallel-gperpendicular| in HfS2:Cr3+ (compound to
      HfS2:V2+) is due to the small local trigonal distortion angle theta rather than
      to the small impurity-ligand distance R in HfS2:Cr3+.

PMID- 16103007
TI  - Developing a national integrated classification of health care interventions in
      Sweden.
AB  - BACKGROUND: Existing classifications in Sweden of health care interventions used
      for quality assurance issues and for decisions on resource allocation does not
      capture all types of health care interventions. The work of professional groups
      like nurses, physiotherapists, and occupational therapists is partly invisible.
      There is a need to develop a classification of health care interventions that
      comprise all activity within the health care sector. AIM: To describe a multi
      professional collaborative work on classification development and to provide
      suggestions for an organizing structure that can capture interventions in the
      health care services incorporating different professional perspectives. RESULTS:
      The professional groups reached a common understanding about the use of the
      classification of The International Classification of Functioning, Disability and
      Health (ICF) as a unifying framework in the classification of health care
      interventions. Proposal was made for a revised structure of a current
      classification of interventions using ICD as unifying framework. CONCLUSION: The
      use of ICF as a unifying framework is seen as a fruitful way of overcoming
      professional differences, and by that supporting the process of reaching a common
      understanding and use of a common language when describing interventions in
      health care.

PMID- 16103008
TI  - Fibrosis progression in chronic hepatitis C patients with occult hepatitis B co
      infection.
AB  - Occult hepatitis B virus (HBV) infection in individuals without hepatitis B
      surface antigen (HBsAg) can be identified in hepatitis C virus (HCV) infected
      patients. However, its role in fibrosis progression remains uncertain. This
      retrospective study compared the fibrosis progression (defined as fibrosis
      progression by at least one stage) and progression to severe fibrosis (fibrosis
      stage 3 or 4) in HCV patients with occult HBV infection. Occult HBV infection was
      diagnosed by the detection of HBV DNA in the serum of 74 consecutive anti-HCV
      positive patients by PCR. Thirty-one patients (41.9%) had occult HBV infection.
      All 74 patients had a median of 2 (range 2-3) liver biopsies. The median time
      between the first and last liver biopsy was 57.7 (range 15.0-132.8) months.
      Eleven of the 31 patients with occult HBV infection compared with 12 of the 43
      patients without occult HBV infection had fibrosis progression (35.5% versus
      27.9%, respectively, p=0.608). Six of the 31 patients with occult HBV infection
      compared with 8 of the 43 patients without occult HBV infection developed severe
      fibrosis (19.4% versus 18.6%, respectively, p=0.946). In conclusion, chronic HCV
      patients with occult HBV co-infection does not seem to progress more than
      patients without occult HBV infection. However, more large-scale studies are
      needed before a definite conclusion can be obtained.

PMID- 16103009
TI  - Physiological responses of Dunaliella salina and Dunaliella tertiolecta to copper
      toxicity.
AB  - Species differences in heavy metal tolerance were investigated by comparing the
      responses of Dunaliella tertiolecta and Dunaliella salina to elevated
      concentrations of CuCl2. Although both species showed reduced cell number ml(-1)
      of algal culture, D. salina was more affected by increase in CuCl2. This reflects
      higher sensitivity of D. salina to CuCl2 compared to D. tertiolecta. Total
      chlorophyll in terms of microg ml(-1) was higher in D. tertiolecta at all tested
      CuCl2 levels, but in terms of microg cell(-1) no significant difference was
      observed between the two species. Total carotenoids in microg cell(-1) increased
      with increase in CuCl2 in both species and it was about five times higher in D.
      salina at all CuCl2 concentrations. While both species showed significant
      increase in lipid peroxidation at elevated CuCl2, the malondialdehyde content of
      D. salina cells was about three times higher at most CuCl2 concentrations.
      Although ascorbate peroxidase (APX) activity increased with increase in CuCl2
      levels in both species, higher activity was observed in D. tertiolecta at all
      tested CuCl2 concentrations. Cu content of D. salina cells was higher than D.
      tertiolecta which may be due to larger volume of D. salina cells. In conclusion,
      since hydroxyl radical (HO*) produced from H2O2 by Cu2+ (Haber-Weiss cycle) is
      involved in lipid peroxidation, higher ascorbate peroxidase activity in D.
      tertiolecta may partly account for lower sensitivity of this species to CuCl2
      compared to D. salina.

PMID- 16103010
TI  - The resurrection of periodic limb movements (PLM): leg activity monitoring and
      the restless legs syndrome (RLS).

PMID- 16103011
TI  - Artificial antigen-presenting cells: artificial solutions for real diseases.
AB  - Adoptive immunotherapy, which involves the transfer of autologous antigen
      specific T cells generated ex vivo, is a promising strategy to treat a variety of
      life-threatening diseases. Unfortunately, current approaches for generating
      sufficient numbers of antigen-specific T cells lack the ability to serve as
      reproducible and economically viable methods. This has spurred the development of
      both cell- and non-cell-based artificial antigen-presenting cells to alleviate
      problems associated with peptide-loaded dendritic cells in current approaches to
      adoptive immunotherapy. Here, we review new strategies for the ex vivo generation
      of antigen-specific T cells and their clinical application. These new approaches
      have the potential to spearhead a new era of successful adoptive immunotherapy
      for cancer and infectious diseases.

PMID- 16103012
TI  - Specificity and isotype of Rh specific antibodies produced by human B-cell lines
      established from alloimmunized Rh negative women.
AB  - Despite the successful outcome of anti-D prophylaxis program, alloimmunization
      still occurs. The aim of this study was to examine the specificity and isotype of
      anti-Rh antibodies in plasma samples of Rh negative alloimmunized individuals and
      to study the same parameters in lymphoblastoid cell lines (LCLs) generated from
      the same donors. Specificity of anti-Rh antibodies was determined in plasma of
      nine alloimmunized subjects by direct hemagglutination using a panel of known RBC
      genotypes and isotype of specific antibodies were identified by an antigen
      specific ELISA. Similar methods were employed to determine specificity and
      isotype of antibodies produced by Rh specific LCLs established from four donors.
      LCLs were generated by Epstein-Barr virus transformation of peripheral blood
      mononuclear cells isolated from each donor followed by their culture over a
      feeder of human fetal fibroblasts. Upon emergence of lymphoblastoid cells,
      culture supernatants were assayed for presence of Rh specific antibody by
      hemagglutination assay. Anti-D was the predominant antibody in both plasma
      samples and among the 128 established LCLs; however, antibodies to other Rh
      specificities namely C and E were also produced. The isotype of anti-Rh antibody
      in all plasma samples was found to be IgG, predominantly IgG1, combined in 7
      samples with IgM. Similarly 76%, 9.2% and 14.8% of LCLs were determined to
      produce antibody of IgG, IgM and of both isotypes, respectively. The data
      supported that the D antigen is the immunodominant component of the Rh system as
      indicated by the in vitro and in vivo profiles of Rh specificities in our
      alloimmunized subjects.

PMID- 16103013
TI  - Modification of the content of plasma protein carbonyl groups in donors after
      granulocyte colony stimulating factor-induced stem cell mobilization.
AB  - Granulocyte-colony stimulating factor (G-CSF), the most established agent for the
      mobilization of stem cells in current clinical practice, could induce a condition
      of oxidative stress. Herein plasmatic levels of protein carbonyl groups (a
      biomarker of oxidative stress) were measured in a group of donors given
      recombinant human G-CSF (rHuG-CSF) at different times: (1) before starting rHuG
      CSF administration, (2) on day 5 of rHuG-CSF administration, (3) on the same day
      immediately after the end of the first leukapheresis procedure and (4) one week
      after rHuG-CSF withdrawal. Plasma levels of protein carbonyl groups enhanced
      significantly in donors after 5 days of rHuG-CSF treatment and appeared further
      slightly increased following leukapheresis procedure; 7 days following rHuG-CSF
      withdrawal, they showed a tendency to normalization. These findings may
      contribute to better understand the oxidative reactions following rHuG-CSF
      treatment and leukapheresis.

PMID- 16103014
TI  - Donors who react may not come back: analysis of repeat donation as a function of
      phlebotomist ratings of vasovagal reactions.
AB  - Previous studies using small or restricted samples suggest that vasovagal
      reactions to blood donation are associated with a decreased likelihood of repeat
      donation. In the present study, we examined data for all allogeneic whole blood
      donors (n=89,587) in the American Red Cross Blood Services, Central Ohio Region
      during an entire year. Results of a one-year follow-up revealed that moderate and
      severe vasovagal reactions reduced the likelihood of repeat donation by 50% or
      more. Light vasovagal reactions, which represented 97% of all reactions recorded,
      significantly reduced return rates by 20% for first-time donors and 33% for
      experienced donors.

PMID- 16103015
TI  - Quantitative and qualitative assessment of circulating NY-ESO-1 specific CD4+ T
      cells in cancer-free individuals.
AB  - The germ cell antigen NY-ESO-1 is characterized by its frequent expression in
      patients bearing cancers of various histological types, that positively
      correlates with stage of disease, together with its frequent spontaneous
      immunogenicity in patients with advanced cancer. Because of these features, NY
      ESO-1 is presently viewed as a prototype antigen for the development of cancer
      vaccines aimed at preventing disease progression. To gain a global view of the
      CD4+ T cell repertoire available for NY-ESO-1 in individuals of different genetic
      background, in this study, we have addressed the presence, frequency, and fine
      specificity of CD4+ T cells reactive against NY-ESO-1-derived sequences among
      circulating lymphocytes from healthy donors. NY-ESO-1 specific CD4+ T cells were
      present among circulating lymphocytes at a frequency between 0.5 and 5 precursors
      per million CD4+ T cells. In the majority of the cases, the reactivity of NY-ESO
      1 specific CD4+ T cells was directed towards immunodominant regions located in
      the carboxyl-terminal half of the protein. Interestingly, immunodominant regions
      were confined to parts of the NY-ESO-1 protein containing hotspot sequences with
      predicted high binding for multiple frequently expressed MHC class II molecules.
      In contrast, no reactivity was found against the amino-terminal part of the
      protein, which was concomitant with the paucity, in this region, of sequences
      with predicted high binding to MHC class II molecules.

PMID- 16103016
TI  - Race/ethnicity: a predictor of temporal lobe epilepsy surgery outcome?
AB  - PURPOSE: The success of epilepsy surgery in temporal lobe epilepsy reaches a 64%
      rate of seizure freedom, based on a randomized control trial. Observational
      studies from epilepsy centers worldwide indicate seizure freedom rates up to 93%
      when the etiology is unilateral hippocampal sclerosis. Several risk factors are
      attributed to the recurrence of seizures following the surgical procedure.
      Nonetheless, whether race influences the outcome of temporal lobe surgery is
      unknown. The purpose of this study was to evaluate if race plays a role in
      outcome following surgery. METHODS: Data were obtained from the discharge
      database of the University of Alabama at Birmingham video/EEG monitoring unit,
      between 1998 and 2003, as well as the clinical charts. Seizure recurrence was
      evaluated 1 year following surgery. The sample consisted of all patients with a
      primary diagnosis of mesial temporal sclerosis (MTS) who underwent anterior
      temporal lobectomy. Multiple logistic regression analysis was used to model the
      presence of seizure recurrence after anterior temporal lobectomy for MTS. Two
      sets of logistic regression models were estimated to generate odds ratios (ORs)
      for seizure recurrence after an anterior temporal lobectomy for African-Americans
      or other possible ethnic/racial group present relative to non-Hispanic
      Caucasians. The first model incorporated only ethnicity as the independent
      variable and generated unadjusted ORs for seizure recurrence following the
      surgical procedure. The second set included the independent variables: duration
      of epilepsy, history of febrile seizures, lateralization of epileptogenic focus,
      handedness, and age. RESULTS: Seventy patients underwent surgical treatment and
      all of them had pathologic confirmation of MTS. Follow-up information for six was
      not available. Analysis of the remaining 64 patients revealed that African
      Americans were more likely than non-Hispanic Caucasians to have seizure
      recurrence after surgery (OR=2.1, 95% CI=0.6-8.0). After potential confounders
      (duration of epilepsy, history of febrile seizures, lateralization of
      epileptogenic focus, handedness, and age) were controlled, this finding did not
      change (OR=1.7, 95% CI=0.3-10.7). CONCLUSION: Our data suggest that race may be
      an important factor related to seizure outcome following temporal lobectomy.

PMID- 16103017
TI  - Absolute pitch: music and beyond.
AB  - "Perfect pitch," known in the scientific literature as "absolute pitch" (AP), is
      a rare phenomenon that has fascinated musicians and scientists alike for over a
      century. There has been a great deal of conflict in the literature between
      advocates of the two main theories on the etiology of AP: some believe that AP is
      learned early in life through intensive musical training, whereas others believe
      AP to be largely innate. Both theories are alike, however, in considering AP to
      be exclusively a musical phenomenon. We propose a paradigm shift by presenting
      here a new model of AP, one that is predicated on two principles: (1) that AP may
      be relatively independent of musical experience; and (2) that there are different
      types of AP, each of which can be ascribed to discrete neurobiological
      mechanisms. We also review data from a diverse series of experiments that were
      designed to test explicitly both the predictions of our model and a series of
      historical myths about AP. In each case, the data strongly support our model. We
      conclude with a general discussion on the nature of AP, the relevance of these
      findings for other areas of research, and future directions of study.

PMID- 16103018
TI  - Extreme obesity in female rats following prepuberal induction of lithium
      pilocarpine seizures and a single injection of acepromazine.
AB  - Seizures were induced in female Wistar albino rats at either 35 or 55 days of age
      with a single systemic injection of lithium (3 mEq/kg) and pilocarpine (30
      mg/kg); the rats were then treated with the atypical neuroleptic acepromazine (25
      mg/kg). These rats manifested progressive weight gain for the rest of their
      lives. The effect was conspicuous by casual observation 6 weeks after treatment
      and occurred primarily in those rats that later developed spontaneous seizures.
      After 1 year, the rats were obese (>1000 g). Such weight gains, associated with
      almost three times the serum triglyceride levels, were not observed in male rats
      and have not been observed in hundreds of female rats that received this
      treatment as adults. Single postseizure injections of ketamine rather than
      acepromazine did not produce this obesity; the weights of these rats were similar
      to those of normal littermates. These results indicate that a single injection of
      a neuroleptic during limbic seizures before puberty can produce neuronal
      alterations that contribute to a lifetime of obesity.

PMID- 16103019
TI  - The role of serotonin in impulsive and aggressive behaviors associated with
      epilepsy-like neuronal hyperexcitability in the amygdala.
AB  - Neuronal hyperexcitability in limbic areas, especially the amygdala, is a
      significant underlying mechanism associated with complex partial seizures (CPS).
      CPS may be comorbid with emotional disturbances, especially major mood disorders,
      anxiety, and aggression. Anticonvulsant medications such as phenytoin are also
      mood-stabilizing, and have been used for treatment of behavioral dyscontrol in
      impulsive aggressive individuals. Because the amygdala has important functional
      roles in epilepsy, emotion, and behavioral control, there may be common
      biological mechanisms involving neuronal excitability that contribute to both
      seizure activity and psychopathology. This review examines physiological
      mechanisms in the amygdala that regulate neuronal excitability and discusses how
      this may underlie, in part, disturbances in emotional behavior.

PMID- 16103021
TI  - Clustering of MAL genes in Hansenula polymorpha: cloning of the maltose permease
      gene and expression from the divergent intergenic region between the maltose
      permease and maltase genes.
AB  - Hansenula polymorpha uses maltase to grow on maltose and sucrose. Inspection of
      genomic clones of H. polymorpha showed that the maltase gene HPMAL1 is clustered
      with genes corresponding to Saccharomyces cerevisiae maltose permeases and MAL
      activator genes orthologues. We sequenced the H. polymorpha maltose permease gene
      HPMAL2 of the cluster. The protein (582 amino acids) deduced from the HPMAL2 gene
      is predicted to have eleven transmembrane domains and shows 39-57% identity with
      yeast maltose permeases. The identity of the protein is highest with maltose
      permeases of Debaryomyces hansenii and Candida albicans. Expression of the HPMAL2
      in a S. cerevisiae maltose permease-negative mutant CMY1050 proved functionality
      of the permease protein encoded by the gene. HPMAL1 and HPMAL2 genes are
      divergently positioned similarly to maltase and maltose permease genes in many
      yeasts. A two-reporter assay of the expression from the HPMAL1-HPMAL2 intergenic
      region showed that expression of both genes is coordinately regulated, repressed
      by glucose, induced by maltose, and that basal expression is higher in the
      direction of the permease gene.

PMID- 16103022
TI  - Roles of replicative and specialized DNA polymerases in frameshift mutagenesis:
      mutability of Salmonella typhimurium strains lacking one or all of SOS-inducible
      DNA polymerases to 26 chemicals.
AB  - Progression of DNA replication is occasionally blocked by endogenous and
      exogenous DNA damage. To circumvent the stalling of DNA replication, cells
      possess a variety of specialized DNA polymerases that replicate through DNA
      damage. Salmonella typhimurium strain TA1538 has six DNA polymerases and four of
      them are encoded by damage-inducible SOS genes, i.e. polB(ST) (pol II), dinB(ST)
      (pol IV), umuDC(ST) (pol V) and samAB. The strain has been used for the detection
      of a variety of chemical mutagens because of the high sensitivity to -2
      frameshift occurring in CGCGCGCG sequence. To assign the role of each DNA
      polymerase in the frameshift mutagenesis, we have constructed the derivatives
      lacking one or all of SOS-inducible DNA polymerases and examined the mutability
      to 26 chemical mutagens. Interestingly, the chemicals could be categorized into
      four classes: class I whose mutagenicity was reduced by the deletion of dinB(ST)
      (1-aminoanthracene and other four chemicals); class II whose mutagenicity was
      reduced by the deletion of either dinB(ST) or umuDC(ST) plus samAB (7,12
      dimethylbenz[a]anthracene and other three chemicals); class III whose
      mutagenicity largely depended on the presence of umuDC(ST) plus samAB (1-N-6
      azabenzo[a]pyrene and other three chemicals) and class IV whose mutagenicity was
      not reduced by deletion of any of the genes encoding SOS-inducible DNA
      polymerases (Glu-P-1 and other 12 chemicals). Deletion of polB(ST) reduced by 30
      60% the mutagenicity of six chemicals of classes II and III. These results
      suggest that multiple DNA polymerases including the replicative DNA polymerase,
      i.e. DNA polymerase III holoenzyme, play important roles in chemically induced -2
      frameshift and also that different sets of DNA polymerases are engaged in the
      translesion bypass of different DNA lesions.

PMID- 16103023
TI  - The quantitative analysis of heroin, methadone and their metabolites and the
      simultaneous detection of cocaine, acetylcodeine and their metabolites in human
      plasma by high-performance liquid chromatography coupled with tandem mass
      spectrometry.
AB  - For a pharmacokinetic-pharmacodynamic study in opioid tolerant patients, who were
      treated with heroin in combination with methadone, a liquid chromatographic assay
      with tandem mass spectrometry detection (LC-MS/MS) was developed for the
      simultaneous determination of heroin, methadone, heroin metabolites 6
      monoacetylmorphine, morphine, and morphine-6 and 3-glucuronide and methadone
      metabolite EMDP. To detect any abuse of substances besides the prescribed opioids
      the assay was extended with the detection of cocaine, its metabolites
      benzoylecgonine and norcocaine and illicit heroin adulterants acetylcodeine and
      codeine. Heroin-d6, morphine-d3, morphine-3-glucuronide-d3 and methadone-d9 were
      used as internal standards. The sample pre-treatment consisted of solid phase
      extraction using mixed mode sorbent columns (MCX Oasis). Chromatographic
      separation was performed at 25 degrees C on a reversed phase Zorbax column with a
      gradient mobile phase consisting of ammonium formate (pH 4.0) and acetonitrile.
      The run time was 15 min. MS with relatively mild electrospray ionisation under
      atmospheric pressure was applied. The triple quadrupole MS was operating in the
      positive ion mode and multiple reaction monitoring (MRM) was used for drug
      quantification. The method was validated over a concentration range of 5-500
      ng/mL for all analytes. The total recovery of heroin varied between 86 and 96%
      and of the heroin metabolites between 76 and 101%. Intra-assay and inter-assay
      accuracy and precision of all analytes were always within the designated limits
      (< or =20% at lower limit of quantification (LLQ) and < or =15% for other
      samples). This specific and sensitive assay was successfully applied in
      pharmacokinetic studies with medically prescribed heroin and toxicological cases.

PMID- 16103024
TI  - Comparison of rat and human alkaline phosphatase isoenzymes and isoforms using
      HPLC and electrophoresis.
AB  - Total activity of alkaline phosphatase (ALP) in serum represents the sum of
      activities of some isoenzymes and their numerous isoforms derived from various
      tissues of the organism. The aim of this work was to separate ALP isoenzymes and
      their isoforms in rat and human serum, compare the properties of serum ALP
      isoforms in rats and humans, and determine the usefulness of some analytical
      methods for specific measurements of ALP isoenzyme and isoform activities. Two
      methods of separation, i.e. high-performance liquid chromatography (HPLC) and
      agarose gel electrophoresis were chosen. The combination of HPLC with
      electrophoresis of the eluted fractions and with ALP inhibition methods (urea, l
      phenylalanine), inactivation (heat) and precipitation (wheat-germ lectins)
      enabled the identification of isoenzymes and isoforms of ALP in serum. Using
      chromatography and a post-column reactor, three isoforms of the intestinal
      isoenzyme and one bone isoform of a tissue non-specific isoenzyme were detected.
      Rat serum differs significantly from human as regards activities of intestinal
      and hepatic isoforms, whereas the properties of the bone isoform are similar in
      both species. Our HPLC method offers a higher resolution than agarose gel
      electrophoresis with respect to ALP subfractions in rat serum.

PMID- 16103025
TI  - Reducing HIV infections at circuit parties: from description to explanation and
      principles of intervention design.
AB  - Circuit parties are weekend-long, erotically charged, drug-prevalent dance events
      attended by up to 25,000 self-identified gay and bisexual men who socialize and
      dance nonstop, sometimes for 24 hours or longer. Although these parties started
      originally as part of the gay community's response to raise HIV/AIDS awareness
      and to build community and cultural identity, they may have become a site for
      transmitting HIV across geographical regions and socioeconomic groups of gay and
      bisexual men. This article reviews the descriptive published studies on circuit
      parties. The authors use these studies and the literature on drug use and high
      risk sexual behavior in gay and bisexual communities, along with sociological and
      social psychological research, to propose a causal model of why circuit parties
      may contribute to unsafe sexual practices that increase HIV infection risk. The
      authors abstract 5 prevention messages relevant to circuit parties and review
      intervention studies in nonparty settings for insight into how to reduce risky
      sexual behavior within circuit events. These intervention studies help to
      identify 5 context-specific groups that can effectively carry the prevention
      messages. The 5-by-5 matrix represents a first stage in developing a causal model
      for reducing HIV infections, along with evaluable principles of intervention, at
      circuit parties.

PMID- 16103026
TI  - New entrants to HIV care are presenting only at marginally earlier stages of
      disease but may increasingly represent groups perceived at lower risk.
AB  - BACKGROUND: Treatment has improved HIV infection prognosis, but whether risk and
      health care seeking behavior have improved is unclear. METHODS: New entrants to
      HIV care at University Hospitals of Cleveland, Ohio, between 1995 and 2002, with
      no history of AIDS-defining illnesses or antiretroviral exposure were included.
      RESULTS: Of new patients, 806 (80%) met the inclusion criteria. Median age
      increased during the study period(35.2 to 38.6 years; P < .001); proportions of
      females and non-whites increased nonsignificantly. Prevalence of AIDS-defining
      illnesses decreased from 1995 to 1996 (25.0% to 14.2%; P <.001) but remained
      stable thereafter. Category B conditions and sexually transmitted diseases
      decreased significantly(31.7% to 9.1%; P = .039 and 22.5% to 8.0%; P = .003), as
      did hepatitis B and C seroprevalence (8.3% to 3.6%; P = .05 and 26.2% to 14.3%; P
      = .003). Median CD4 counts and HIV RNA did not change significantly. CONCLUSIONS:
      Prevalence of Category B conditions, sexually transmitted diseases, and hepatitis
      B and C declined significantly in this study. Prevalence of AIDS-defining
      illnesses decreased early in the highly active antiretroviral therapy era only,
      whereas markers of HIV disease stage remained stable, suggesting a need for
      earlier recognition of infection. Decreasing sexually transmitted diseases and
      hepatitis coinfections suggest that HIV infection is increasingly seen in
      populations previously perceived at lower risk.

PMID- 16103027
TI  - Effect of the CTL proliferation program on virus dynamics.
AB  - Experiments have established that CTLs do not require continuous antigenic
      stimulation for expansion. Instead, responses develop by a process of programmed
      proliferation which involves approximately 7-10 antigen-independent cell
      divisions, the generation of effector cells and the differentiation into memory
      cells. The effect of this program on the infection dynamics and the advantages
      gained by the program have, however, not been explored yet. We investigate this
      with mathematical models. We find that more programmed divisions can make virus
      clearance more efficient because CTL division continues to occur independent from
      antigenic stimulation when virus load drops to low levels. This results in
      stronger effector activity at low virus loads, and in a higher chance of virus
      extinction. On the other hand, the more programmed divisions occur, the less
      efficient the response is at preventing high acute virus loads and thus acute
      symptoms. The reason is that the programmed divisions are independent from
      antigenic stimulation, and an increase in virus load does not speed up the rate
      of CTL expansion. We hypothesize that the 7-10 programmed divisions observed in
      vivo represent an optimal solution to this trade-off which maximizes the chances
      to clear, while preventing excessive acute pathology. If the CTLs fail to clear
      the virus, however, we find that the properties of the programmed proliferation
      model are very similar to those derived from models which assume continuous
      antigenic stimulation. We discuss these results in the context of data from
      murine virus infections and explore implications for virus dynamics in CD4 helper
      deficient hosts.

PMID- 16103028
TI  - Expression of the Ian family of putative GTPases during T cell development and
      description of an Ian with three sets of GTP/GDP-binding motifs.
AB  - Reports suggest that two members of the novel immune-associated nucleotide (Ian)
      GTPase family, Ian1 and Ian5, play roles in T cell development. We performed real
      time PCR analysis of the expression of Ian genes of the rat during T cell
      maturation, in macrophages and in cell lines. We found that all of the genes were
      expressed at relatively low levels at the early double-negative thymocyte stage
      but were expressed more strongly at later cell stages. Our study also revealed
      the fact that the previously reported Ian9, Ian10 and Ian11 genes are, instead,
      parts of a single gene for which we retain the name Ian9, potentially encoding a
      GTPase with a highly unusual triplicated structure. Antisera were developed
      against both Ian1 and Ian9. We established that Ian9 is produced as an
      approximately 75-kDa protein in both T cells and thymocytes. We observed that
      levels of both Ian1 and Ian9 proteins are profoundly reduced in T cells from
      lymphopenic rats as compared with wild-type rats. It was demonstrated that
      thymocytes and B cells from lymphopenic rats (Ian5 null) did not show enhanced
      sensitivity to gamma-irradiation-induced apoptosis.

PMID- 16103029
TI  - IgE- and FcepsilonRI-mediated migration of human basophils.
AB  - Local accumulation of basophils at inflammatory sites is observed in experimental
      antigen challenge and in allergic diseases. It is not fully known what factor(s)
      regulates local basophil influx in tissues, and it has not been determined
      whether antigens belong in a panel of basophil chemoattractants. This study was
      designed to elucidate whether IgE- and high-affinity receptor for IgE
      (FcepsilonRI)-mediated stimulation can induce human basophil migration. The
      migration-inducing potency of an anti-FcepsilonRI alpha-chain mAb, CRA-1, was
      examined on human basophils. CRA-1 mAb elicited significant migration of
      basophils. The migration-inducing potency of this mAb was maximal at 100 ng ml-1,
      and CRA-1 mAb at 100 ng ml-1 attracted approximately 10% of total inoculated
      basophils above baseline levels after incubation for 2.5 h. Checkerboard analysis
      indicated that basophil migration induced by this mAb was mainly chemotactic and
      partially chemokinetic. An antigen, Der f 2, also induced migration of basophils
      from Der f-sensitive subjects. Basophils mixed with 1 ng ml-1 of CRA-1 mAb showed
      an exaggerated migration response to eotaxin, indicating that FcepsilonRI cross
      linkage enhances basophil migration to other chemoattractants. Induction of
      basophil migration by IgE- and FcepsilonRI-cross-linking stimulation may, at
      least in part, explain the pathogenesis of local basophil accumulation clinically
      observed in allergic diseases such as asthma.

PMID- 16103030
TI  - Estimating the high risk group for cardiovascular disease in the Norwegian HUNT 2
      population according to the 2003 European guidelines: modelling study.
AB  - OBJECTIVE: To estimate the high risk group for cardiovascular disease in a well
      defined Norwegian population according to European guidelines and the systematic
      coronary risk evaluation system. DESIGN: Modelling study. SETTING: Nord-Trondelag
      health study 1995-7 (HUNT 2), Norway. PARTICIPANTS: 5548 participants of the Nord
      Trondelag health study 1995-7, aged 40, 50, 55, 60, and 65. MAIN OUTCOME
      MEASURES: Distribution of risk categories for cardiovascular disease, with
      emphasis on the high risk group. MAIN RESULTS: At age 40, 22.5% (95% confidence
      interval 19.3% to 25.7%) of women and 85.9% (83.2% to 88.6%) of men were at high
      risk of cardiovascular disease. Corresponding numbers at age 50 were 39.5% (35.9%
      to 43.1%) and 88.7% (86.3% to 91.0%) and at age 65 were 84.0% (80.6% to 87.4%)
      and 91.6% (88.6% to 94.1%). At age 40, one out of 10 women and no men would be
      classified at low risk for cardiovascular disease. CONCLUSION: Implementation of
      the 2003 European guidelines on prevention of cardiovascular disease in clinical
      practice would classify most adult Norwegians at high risk for fatal
      cardiovascular disease.

PMID- 16103031
TI  - Self reported stress and risk of breast cancer: prospective cohort study.
AB  - OBJECTIVE: To assess the relation between self reported intensity and frequency
      of stress and first time incidence of primary breast cancer. DESIGN: Prospective
      cohort study with 18 years of follow-up. SETTING: Copenhagen City heart study,
      Denmark. PARTICIPANTS: The 6689 women participating in the Copenhagen City heart
      study were asked about their perceived level of stress at baseline in 1981-3.
      These women were followed until 1999 in the Danish nationwide cancer registry,
      with < 0.1% loss to follow-up. MAIN OUTCOME MEASURE: First time incidence of
      primary breast cancer. RESULTS: During follow-up 251 women were diagnosed with
      breast cancer. After adjustment for confounders, women with high levels of stress
      had a hazard ratio of 0.60 (95% confidence interval 0.37 to 0.97) for breast
      cancer compared with women with low levels of stress. Furthermore, for each
      increase in stress level on a six point stress scale an 8% lower risk of primary
      breast cancer was found (hazard ratio 0.92, 0.85 to 0.99). This association
      seemed to be stable over time and was particularly pronounced in women receiving
      hormone therapy. CONCLUSION: High endogenous concentrations of oestrogen are a
      known risk factor for breast cancer, and impairment of oestrogen synthesis
      induced by chronic stress may explain a lower incidence of breast cancer in women
      with high stress. Impairment of normal body function should not, however, be
      considered a healthy response, and the cumulative health consequences of stress
      may be disadvantageous.

PMID- 16103032
TI  - Randomised controlled trial of acute mental health care by a crisis resolution
      team: the north Islington crisis study.
AB  - OBJECTIVE: To evaluate the effectiveness of a crisis resolution team. DESIGN:
      Randomised controlled trial. PARTICIPANTS: 260 residents of the inner London
      Borough of Islington who were experiencing crises severe enough for hospital
      admission to be considered. INTERVENTIONS: Acute care including a 24 hour crisis
      resolution team (experimental group), compared with standard care from inpatient
      services and community mental health teams (control group). MAIN OUTCOME
      MEASURES: Hospital admission and patients' satisfaction. RESULTS: Patients in the
      experimental group were less likely to be admitted to hospital in the eight weeks
      after the crisis (odds ratio 0.19, 95% confidence interval 0.11 to 0.32), though
      compulsory admission was not significantly reduced. A difference of 1.6 points in
      the mean score on the client satisfaction questionnaire (CSQ-8) was not quite
      significant (P = 0.07), although it became so after adjustment for baseline
      characteristics (P = 0.002). CONCLUSION: Crisis resolution teams can reduce
      hospital admissions in mental health crises. They may also increase satisfaction
      in patients, but this was an equivocal finding.

PMID- 16103033
TI  - Dose-effect relation between daily ethanol intake in the range 0-70 grams and
      %CDT value: validation of a cut-off value.
AB  - AIM: To evaluate the ability to infer alcohol consumption using the %CDT
      (carbohydrate deficient transferrin) immunoassay (Axis Shield). METHODS: One
      hundred and eighty-three healthy subjects (143 men, 40 women) undergoing a
      routine medical check-up at their workplace declared frequency and quantity of
      alcohol consumption covering the last 4 weeks. Seven sub-groups were made up from
      this population, according to daily ethanol intake and by increments of 10 g from
      0 to 70 g/day. A reference group that consisted of 133 healthy teetotallers (74
      men, 59 women) was recruited by occupational medicine in the same conditions as
      the 183 subjects of the study. Percentage CDT and gamma glutamyl transferase
      (GGT) were assayed on a fasting blood sample. RESULTS: There was a proportional
      dose-response effect of daily ethanol intake on %CDT values in the range of 0-70
      g per day. A threshold effect on %CDT values for patients having an alcohol
      intake of over 40 g per day was found, an effect which was not observed for GGT
      activity. CONCLUSION: The kit has clinical usefulness, and the value of 2.6%
      proposed by the manufacturer for the cut-off for hazardous drinking in both sexes
      has been validated.

PMID- 16103034
TI  - Economic evaluation of interventions for problem drinking and alcohol dependence:
      cost per QALY estimates.
AB  - AIMS: To compare the performance of competing and complementary interventions for
      prevention or treatment of problem drinking and alcohol dependence. To provide an
      example of how health maximising decision-makers might use performance measures
      such as cost per quality adjusted life year (QALY) league tables to formulate an
      optimal package of interventions for problem drinking and alcohol dependence.
      METHODS: A time-dependent state-transition model was used to estimate QALYs
      gained per person for each intervention as compared to usual care in the relevant
      target population. RESULTS: Cost per QALY estimates for each of the interventions
      fall below any putative funding threshold for developed economies. Interventions
      for problem drinkers appear to offer better value than interventions targeted at
      those with a history of severe physical dependence. CONCLUSIONS: Formularies such
      as Australia's Medicare should include a comprehensive package of interventions
      for problem drinking and alcohol dependence.

PMID- 16103035
TI  - Combining the audit questionnaire and biochemical markers to assess alcohol use
      and risk of alcohol withdrawal in medical inpatients.
AB  - AIMS: Alcohol consumption is often under-reported in patients admitted to general
      hospitals with acute illness. For alcohol-dependent individuals hospital
      admission results in an enforced period of abstinence with potential alcohol
      withdrawal symptoms, and possible life threatening complications. Early detection
      of alcohol use is therefore beneficial to patients and health services. The
      purpose of this study was to investigate the performance of the alcohol use
      disorders identification test (AUDIT) questionnaire in the acute medical setting,
      and the effect of combining routine biological markers-glutamyltransferase,
      alanine aminotransferase, aspartate aminotransferase, and mean corpuscular volume
      (MCV) on its performance in the early identification of in-patients with alcohol
      use disorders and at risk of developing symptoms of alcohol withdrawal. METHODS:
      Prospective study in consecutive patients admitted to an acute medical admissions
      ward. All patients were screened using the AUDIT questionnaire and routine blood
      tests. Patients were then monitored for symptoms of withdrawal using clinical
      institute withdrawal assessment for alcohol (CIWA-Ar). RESULTS: Of the 874
      patients screened using the AUDIT, 98 (11%) screened positive of whom 17 (2% of
      the 874) experienced clinically significant alcohol withdrawal symptoms, when
      using serial CIWA-Ar. The AUDIT and serial CIWA-Ar detected all patients who went
      on to manifest acute withdrawal symptoms. There was no loss of sensitivity at an
      AUDIT cut-off of 13 or more compared with the lower cut-off of 8 or more. A
      positive predictive value of 17.3% for an AUDIT score of 8 or more in the
      detection of withdrawal, increased to 47.1% when found in combination with at
      least two abnormal biological markers whilst maintaining a sensitivity of 94.1%
      and specificity of 97.9%. CONCLUSION: These findings confirm that AUDIT is a
      useful alcohol screen in general medical settings and that its ability to
      correctly predict which patients will experience alcohol withdrawal is increased
      when used in combination with biological markers.

PMID- 16103036
TI  - Effects of nitrogen deficiency on photosynthetic traits of maize hybrids released
      in different years.
AB  - BACKGROUND AND AIMS: New maize (Zea mays) hybrids outperformed old ones even at
      reduced N rates. Understanding the mechanisms of the differences in performance
      between newer and older hybrids under N deficiency could provide avenues for
      breeding maize cultivars with large yield under N deficiency, and reduce
      environmental pollution caused by N fertilizers. METHODS: N deficiency effects on
      grain weight, plant weight, harvest index, leaf area and photosynthetic traits
      were studied in the field for six maize hybrids released during the past 50 years
      to compare their tolerance and to explore their physiological mechanisms. KEY
      RESULTS: N deficiency decreased grain yield and plant weight in all hybrids,
      especially in the older hybrids. However, there was no significant difference in
      harvest index, rate of light-saturated photosynthesis (Psat) 20 d before
      flowering, leaf area or plant weight at flowering between the N-deficient and
      control plants of all hybrids. Dry matter production after flowering of the N
      deficient plants was significantly lower than that of the control plants in all
      hybrids, especially in the older hybrids, and was mostly due to differences in
      the rate of decrease in photosynthetic capacity during this stage. The lower Psat
      of the older hybrids was not due to stomatal limitation, as there was no
      significant difference in stomatal conductance (gs) and intercellular CO2
      concentration (Ci) between the hybrids. N deficiency accelerated senescence, i.e.
      decreased chlorophyll and soluble protein contents, after anthesis more for the
      earlier released hybrids than for the later ones. N deficiency decreased
      phosphoenolpyruvate carboxylase (PEPCase) activity significantly more in older
      hybrids than newer hybrids, and affected the maximal efficiency of PSII
      photochemistry (Fv/Fm) only in the old hybrids and at the late stage.
      CONCLUSIONS: Compared with older (earlier released) hybrids, newer (later
      released) hybrids maintained greater plant and grain weight under N deficiency
      because their photosynthetic capacity decreased more slowly after anthesis,
      associated with smaller non-stomatal limitations due to maintenance of PEPCase
      activity, and chlorophyll and soluble protein content.

PMID- 16103037
TI  - A morphological study of the Petunia integrifolia complex (Solanaceae).
AB  - BACKGROUND AND AIMS: Petunia inflata has been treated taxonomically in various
      ways: it has been described as an independent species, treated as a synonym of P.
      integrifolia, and also regarded as a subspecies of P. integrifolia. The present
      study was designed to resolve the ambiguity involving the P. integrifolia complex
      (P. integrifolia plus P. inflata). METHODS: Tentative identification (either
      integrifolia group or inflata group) was carried out in the field based on the
      observation of live specimens at the restricted type localities. The accuracy of
      the tentative identification was later tested with principal component and
      cluster analyses of data obtained by measuring 21 morphological characters on
      cultivated live specimens sourced from 113 natural populations of the P.
      integrifolia complex in Argentina, Brazil, Paraguay and Uruguay. KEY RESULTS:
      There was a clear, statistically significant gap between the morphological
      measurements of the two groups, ensuring the accuracy of identification carried
      out in the field except for a probable hybrid swarm. Previously, the condition of
      the pedicel in the fruiting state was considered an important character
      distinguishing between these two groups; however, the condition of the pedicel
      was rather variable in the integrifolia group. The two groups were found to have
      geographically distinct distributions: the integrifolia group occurred in
      southern regions, whereas the inflata group occurred in northern regions.
      CONCLUSIONS: Based on the available evidence, it is suggested that the two groups
      are allopatric species, P. integrifolia and P. inflata, in agreement with the
      opinion of Fries (1911).

PMID- 16103038
TI  - Phylogeographical variation of chloroplast DNA in cork oak (Quercus suber).
AB  - BACKGROUND AND AIMS: In the last decades, the geographical location of the centre
      of origin of Quercus suber (cork oak), a strictly western Mediterranean oak
      species, has been the subject of controversy. METHODS: RFLP variation over the
      whole chloroplast DNA molecule and PCR-RFLPs over seven specific cpDNA fragments
      were analysed phylogeographically to reconstruct the evolutionary history of cork
      oak. KEY RESULTS: Nine chlorotypes of the 'suber' cpDNA lineage were identified
      throughout the species range. Using closely related Mediterranean oak species as
      outgroup, the chlorotypes showed a clear phylogeographical pattern of three
      groups corresponding to potential glacial refuges in Italy, North Africa and
      Iberia. The most ancestral and recent groups were observed in populations located
      in the eastern and western parts of the species range, respectively. Several
      unrelated chlorotypes of the 'ilex' cpDNA lineage were also identified in
      specific western areas. CONCLUSIONS: The results support a Middle-Eastern or a
      central Mediterranean origin for cork oak with subsequent westward colonization
      during the Tertiary Period, and suggest that the 'ilex' chlorotype variation does
      not reflect entirely cytoplasmic introgression by Q. ilex but originated partly
      in Q. suber.

PMID- 16103039
TI  - Recommendations for the management of patients after heart valve surgery.
AB  - Approximately 50,000 valve replacement operations take place in Europe annually
      and almost as many valve repair procedures. Previous European guidelines on
      management of patients after valve surgery were last published in 1995 and were
      limited to recommendations about antithrombotic prophylaxis. American guidelines
      covering the broader topic of the investigation and treatment of patients with
      valve disease were published in 1998 but devoted relatively little space to post
      surgical management. This document represents the consensus view of a committee
      drawn from three European Society of Cardiology (ESC) Working Groups (WG): the WG
      on Valvular Heart Disease, the WG on Thrombosis, and the WG on Rehabilitation and
      Exercise Physiology. In almost all areas of patient management after valve
      surgery, randomized trials and meta-analyses do not exist. Such randomized trials
      as do exist are very few in number, are narrowly focused with small numbers, have
      limited general applicability, and do not lend themselves to meta-analysis
      because of widely divergent methodologies and different patient characteristics.
      Recommendations are therefore almost entirely based on non-randomized studies and
      relevant basic science.

PMID- 16103040
TI  - Moving proximally through the intersection between the process and the content of
      care in ST-elevation myocardial infarction.

PMID- 16103041
TI  - Cardiac 123I-MIBG scintigraphy in patients with drug induced parkinsonism.
AB  - Cardiac sympathetic dysfunction was investigated using 123I
      metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 20 patients with drug
      induced parkinsonism (DIP). The mean heart to mediastinum ratio was significantly
      greater in patients with DIP than in those with Parkinson's disease (mean (SD):
      2.07 (0.39) v 1.28 (0.15), p<0.001). MIBG uptake was not different between the
      DIP patients and controls. Two DIP patients whose MIBG uptake was significantly
      reduced showed persistent parkinsonism and responded dramatically to levodopa.

PMID- 16103042
TI  - Laing early onset distal myopathy: slow myosin defect with variable abnormalities
      on muscle biopsy.
AB  - BACKGROUND: Laing early onset distal myopathy (MPD1) is an autosomal dominant
      myopathy caused by mutations within the slow skeletal muscle fibre myosin heavy
      chain gene, MYH7. It is allelic with myosin storage myopathy, with the commonest
      form of familial hypertrophic cardiomyopathy, and with one form of dilated
      cardiomyopathy. However, the clinical picture of MPD1 is distinct from these
      three conditions. OBJECTIVE: To collate and discuss the histological features
      reported in the muscle biopsies of MPD1 patients and to outline the clinical
      features. RESULTS: The phenotype of MPD1 was consistent, with initial weakness of
      great toe/ankle dorsiflexion, and later development of weakness of finger
      extension and neck flexion. Age of onset was the only variable, being from birth
      up to the 20 s, but progression was always very slow. The pathological features
      were variable. In this retrospective series, there were no pathognomonic
      diagnostic features, although atrophic type I fibres were found in half the
      families. Rimmed vacuoles are consistently seen in all other distal myopathies
      with the exception of Myoshi distal myopathy. However, they were found in a
      minority of patients with MPD1, and were not prominent when present.
      Immunohistochemical staining for slow and fast myosin showed co-expression of
      slow and fast myosin in some type I fibres, possibly indicating a switch to type
      II status. This may be a useful aid to diagnosis. CONCLUSIONS: The pathological
      findings in MPD1 are variable and appear to be affected by factors such as the
      specific muscle biopsied, the age of the patient at biopsy, and the duration of
      disease manifestations.

PMID- 16103043
TI  - Critical thresholds of intracranial pressure and cerebral perfusion pressure
      related to age in paediatric head injury.
AB  - BACKGROUND: The principal strategy for managing head injury is to reduce the
      frequency and severity of secondary brain insults from intracranial pressure
      (ICP) and cerebral perfusion pressure (CPP), and hence improve outcome. Precise
      critical threshold levels have not been determined in head injured children.
      OBJECTIVE: To create a novel pressure-time index (PTI) measuring both duration
      and amplitude of insult, and then employ it to determine critical insult
      thresholds of ICP and CPP in children. METHODS: Prospective, observational,
      physiologically based study from Edinburgh and Newcastle, using patient monitored
      blood pressure, ICP, and CPP time series data. The PTI for ICP and CPP for 81
      children, using theoretical values derived from physiological norms, was varied
      systematically to derive critical insult thresholds which delineate Glasgow
      outcome scale categories. RESULTS: The PTI for CPP had a very high predictive
      value for outcome (receiver operating characteristic analyses: area under curve =
      0.957 and 0.890 for mortality and favourable outcome, respectively) and was more
      predictive than for ICP. Initial physiological values most accurately predicted
      favourable outcome. The CPP critical threshold values determined for children
      aged 2-6, 7-10, and 11-15 years were 48, 54, and 58 mm Hg. respectively.
      CONCLUSIONS: The PTI is the first substantive paediatric index of total ICP and
      CPP following head injury. The insult thresholds generated are identical to age
      related physiological values. Management guidelines for paediatric head injuries
      should take account of these CPP thresholds to titrate appropriate pressor
      therapy.

PMID- 16103044
TI  - Neuropsychological characteristics of mild cognitive impairment subgroups.
AB  - OBJECTIVE: To describe the neuropsychological characteristics of mild cognitive
      impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS)
      cognition study. METHODS: MCI was classified as MCI-amnestic type (MCI-AT):
      patients with documented memory deficits but otherwise normal cognitive function;
      and MCI-multiple cognitive deficits type (MCI-MCDT): impairment of at least one
      cognitive domain (not including memory), or one abnormal test in at least two
      other domains, but who had not crossed the dementia threshold. The MCI subjects
      did not have systemic, neurological, or psychiatric disorders likely to affect
      cognition. RESULTS: MCI-AT (n = 10) had worse verbal and non-verbal memory
      performance than MCI-MCDT (n = 28) or normal controls (n = 374). By contrast, MCI
      MCDT had worse language, psychomotor speed, fine motor control, and
      visuoconstructional function than MCI-AT or normal controls. MCI-MCDT subjects
      had memory deficits, though they were less pronounced than in MCI-AT. Of the MCI
      MCDT cases, 22 (78.5%) had memory deficits, and 6 (21.5%) did not. MCI-MCDT with
      memory disorders had more language deficits than MCI-MCDT without memory
      disorders. By contrast, MCI-MCDT without memory deficits had more fine motor
      control deficits than MCI-MCDT with memory deficits. CONCLUSIONS: The most
      frequent form of MCI was the MCI-MCDT with memory deficits. However, the
      identification of memory impaired MCI groups did not reflect the true prevalence
      of MCI in a population, as 16% of all MCI cases and 21.5% of the MCI-MCDT cases
      did not have memory impairment. Study of idiopathic amnestic and non-amnestic
      forms of MCI is essential for an understanding of the aetiology of MCI.

PMID- 16103045
TI  - Comparative models of GABAA receptor extracellular and transmembrane domains:
      important insights in pharmacology and function.
AB  - Comparative models of the extracellular and transmembrane domains of GABAA
      receptors in the agonist-free state were generated based on the recently
      published structures of the nicotinic acetylcholine receptor. The models were
      validated by computational methods, and their reliability was estimated by
      analyzing conserved and variable elements of the cys-loop receptor topology. In
      addition, the methodological limits in the interpretation of such anion channel
      receptor models are discussed. Alignment ambiguities in the helical domain were
      resolved for helix 3 by placing two gaps into the linker connecting helices 2 and
      3. The resulting models were shown to be consistent with a wide range of
      pharmacological and mutagenesis data from GABAA and glycine receptors. The loose
      packing of the models results in a large amount of solvent-accessible space and
      offers a natural explanation for the rich pharmacology and the great flexibility
      of these receptors that are known to exist in numerous drug-induced
      conformational states. Putative drug binding pockets found within and between
      subunits are described, and amino acid residues important for the action and
      subtype selectivity of volatile and intravenous anesthetics, barbiturates, and
      furosemide are shown to be part of these pockets. The entire helical domain,
      however, seems to be crucial not only for binding of drugs but also for
      transduction of binding to gating or of allosteric modulation. These models can
      now be used to design new experiments for clarification of pharmacological and
      structural questions as well as for investigating and visualizing drug induced
      conformational changes.

PMID- 16103046
TI  - A prodrug of cysteine, L-2-oxothiazolidine-4-carboxylic acid, regulates vascular
      permeability by reducing vascular endothelial growth factor expression in asthma.
AB  - Inflammation of the asthmatic airway is usually accompanied by increased vascular
      permeability and plasma exudation. Oxidative stress plays critical roles in
      airway inflammation. Although reactive oxygen species (ROS) are shown to cause
      vascular leakage, the mechanisms by which ROS induce increased vascular
      permeability are not clearly understood. We have used a murine model of asthma to
      evaluate the effect of l-2-oxothiazolidine-4-carboxylic acid (OTC), a prodrug of
      cysteine that acts as an antioxidant, more specifically in the increase of
      vascular permeability. These mice develop the following typical
      pathophysiological features of asthma in the lungs: increased numbers of
      inflammatory cells of the airways, airway hyper-responsiveness, increased
      vascular permeability, and increased levels of vascular endothelial growth factor
      (VEGF). Administration of OTC markedly reduced plasma extravasation and VEGF
      levels in allergen-induced asthmatic lungs. We also showed that at 72 h after
      ovalbumin inhalation, increased levels of hypoxia-inducible factor-1alpha (a
      transcriptional activator of VEGF) in nuclear protein extracts of lung tissues
      were decreased by the administration of OTC. These results indicate that OTC
      modulates vascular permeability by lowering VEGF expression.

PMID- 16103047
TI  - The neurotrophic receptor TrkB in anoikis resistance and metastasis: a
      perspective.
AB  - Resistance to anoikis ("detachment-induced apoptosis") has been suggested to be a
      prerequisite for cancer cells to metastasize. In a functional screen for
      suppressors of anoikis, we identified the neurotrophic receptor TrkB. Upon s.c.
      inoculation in mice, TrkB-expressing cells formed highly invasive and metastatic
      tumors. Here, we discuss our findings within the context of the proposed role of
      TrkB in human malignancies and address the question of its feasibility as a
      target for cancer therapy.

PMID- 16103048
TI  - Restarting the cell cycle when the checkpoint comes to a halt.
AB  - The DNA damage checkpoint coordinates a block in cell proliferation with the DNA
      repair process that follows when lesions are inflicted on the genome. However, we
      do not know exactly how cell division can recommence following a DNA damage
      induced arrest. Recent work from our lab has identified Polo-like kinase-1 and
      Cdc25B as two essential components of the machinery that sets the cell division
      process back in motion when the checkpoint response is abrogated. Here, we
      discuss these novel insights and discuss their possible implications for the
      treatment of cancer.

PMID- 16103049
TI  - Expanding the use of magnetic resonance in the assessment of tumor response to
      therapy: workshop report.
AB  - Although dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and
      magnetic resonance spectroscopy (MRS) have great potential to provide routine
      assessment of cancer treatment response, their widespread application has been
      hampered by a lack of standards for use. Thus, the National Cancer Institute
      convened a workshop to assess developments and applications of these methods,
      develop standards for methodology, and engage relevant partners (drug and device
      industries, researchers, clinicians, and government) to encourage sharing of data
      and methodologies. Consensus recommendations were reached for DCE-MRI
      methodologies and the focus for initial multicenter trials of MRS. In this
      meeting report, we outline the presentations, the topics discussed, the ongoing
      challenges identified, and the recommendations made by workshop participants for
      the use of DCE-MRI and 1H MRS in the clinical assessment of antitumor therapies.

PMID- 16103050
TI  - Low-dose metronomic combined with intermittent bolus-dose cyclophosphamide is an
      effective long-term chemotherapy treatment strategy.
AB  - Metronomic chemotherapy refers to the close, regular administration of
      comparatively low doses of cytotoxic drugs, with minimal or no drug-free breaks,
      over prolonged periods. It is thought to have an antiangiogenic basis. However,
      whereas surprisingly durable and potent tumor responses have been observed in a
      number of preclinical tumor models, relapses usually eventually occur using this
      type of treatment strategy. We therefore decided to test modified metronomic
      chemotherapy regimens that might significantly delay such relapses, but still
      maintain modest and acceptable toxicity profiles. Here, we show that repeated
      administration of bolus doses (BDs) of cyclophosphamide every 3 or 6 weeks,
      combined with a daily oral low-dose metronomic (LDM) regimen (20 mg/kg/d
      cyclophosphamide), improves efficacy and significantly delays progression of
      transplanted PC-3 human prostate cancer xenografts, syngeneic transplanted EMT-6
      breast tumors, and "spontaneous" murine erythroleukemia. Efficacy was superior
      whereas toxicity was mild and comparable to the LDM regimen, the latter assessed
      by body weight, neutrophil, lymphocyte, and total white blood counts.
      Antiangiogenic activity, measured by reduction in circulating endothelial
      precursor cells, revealed that the greatest degree of suppression occurred using
      the combination treatment. Overall, our results indicate that the administration
      of intermittent BD combined with chronic oral LDM cyclophosphamide is a potent
      treatment regimen for controlling tumor growth, which has a low toxicity profile,
      over prolonged periods of time.

PMID- 16103051
TI  - Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian
      target of rapamycin inhibition.
AB  - The mammalian target of rapamycin (mTOR) has emerged as an important cancer
      therapeutic target. Rapamycin and its derivatives that specifically inhibit mTOR
      are now being actively evaluated in clinical trials. Recently, the inhibition of
      mTOR has been shown to reverse Akt-dependent prostate intraepithelial neoplasia.
      However, many cancer cells are resistant to rapamycin and its derivatives. The
      mechanism of this resistance remains a subject of major therapeutic significance.
      Here we report that the inhibition of mTOR by rapamycin triggers the activation
      of two survival signaling pathways that may contribute to drug resistance.
      Treatment of human lung cancer cells with rapamycin suppressed the
      phosphorylation of p70S6 kinase and 4E-BP1, indicating an inhibition of mTOR
      signaling. Paradoxically, rapamycin also concurrently increased the
      phosphorylation of both Akt and eIF4E. The rapamycin-induced phosphorylation of
      Akt and eIF4E was suppressed by the phosphatidylinositol-3 kinase (PI3K)
      inhibitor LY294002, suggesting the requirement of PI3K in this process. The
      activated Akt and eIF4E seem to attenuate rapamycin's growth-inhibitory effects,
      serving as a negative feedback mechanism. In support of this model, rapamycin
      combined with LY294002 exhibited enhanced inhibitory effects on the growth and
      colony formation of cancer cells. Thus, our study provides a mechanistic basis
      for enhancing mTOR-targeted cancer therapy by combining an mTOR inhibitor with a
      PI3K or Akt inhibitor.

PMID- 16103052
TI  - Apoptin nuclear accumulation is modulated by a CRM1-recognized nuclear export
      signal that is active in normal but not in tumor cells.
AB  - Tumor cell-specific activity of chicken anemia virus viral protein 3 (VP3 or
      apoptin) is believed to be dependent on its ability to localize in the nucleus of
      transformed but not of primary or nontransformed cells. The present study
      characterizes the signals responsible for the novel nucleocytoplasmic trafficking
      properties of VP3 using two isogenic tumor/nontumor cell pairs. In addition to
      the tumor cell-specific nuclear targeting signal, comprising two stretches of
      basic amino acids in the VP3 COOH terminus which are highly efficient in tumor
      but not in normal cells, we define the CRM1-recognized nuclear export sequence
      (NES) within the VP3 tumor cell-specific nuclear targeting signal for the first
      time. Intriguingly, the NES (amino acids 97-105) is functional in normal but not
      in tumor cells through the action of the threonine 108 phosphorylation site
      adjacent to the NES which inhibits its action. In addition, we characterize a
      leucine-rich sequence (amino acids 33-46) that assists VP3 nuclear accumulation
      by functioning as a nuclear retention sequence, conferring association with
      promyelocytic leukemia nuclear bodies. This unique combination of signals is the
      basis of the tumor cell-specific nuclear targeting abilities of VP3.

PMID- 16103053
TI  - MicroRNA gene expression deregulation in human breast cancer.
AB  - MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene
      expression by targeting mRNAs and triggering either translation repression or RNA
      degradation. Their aberrant expression may be involved in human diseases,
      including cancer. Indeed, miRNA aberrant expression has been previously found in
      human chronic lymphocytic leukemias, where miRNA signatures were associated with
      specific clinicobiological features. Here, we show that, compared with normal
      breast tissue, miRNAs are also aberrantly expressed in human breast cancer. The
      overall miRNA expression could clearly separate normal versus cancer tissues,
      with the most significantly deregulated miRNAs being mir-125b, mir-145, mir-21,
      and mir-155. Results were confirmed by microarray and Northern blot analyses. We
      could identify miRNAs whose expression was correlated with specific breast cancer
      biopathologic features, such as estrogen and progesterone receptor expression,
      tumor stage, vascular invasion, or proliferation index.

PMID- 16103054
TI  - Hepatocyte growth factor/scatter factor differentially regulates expression of
      proangiogenic factors through Egr-1 in head and neck squamous cell carcinoma.
AB  - Hepatocyte growth factor/scatter factor (HGF) and the angiogenesis factors
      platelet-derived growth factors (PDGF), vascular endothelial growth factor
      (VEGF), and interleukin-8 (IL-8) are found in elevated concentrations in serum or
      tumor tissue of patients with head and neck squamous cell carcinomas (HNSCC),
      suggesting these factors may be coregulated. A cDNA microarray analysis for HGF
      inducible genes revealed that HGF also modulates PDGFA expression, a gene
      recently shown to be inducible by the transcription factor, early growth response
      1 (Egr-1). In the present study, we investigated the potential role of HGF
      induced Egr-1 in expression of PDGF, VEGF, and IL-8. HGF induced expression of
      all three factors and Egr-1 expression and DNA-binding activity. The analysis of
      promoter sequences showed putative Egr-1 binding sites in the PDGFA or VEGF but
      not in the IL-8 promoter, and HGF-induced Egr-1-binding activity was confirmed by
      chromatin immunoprecipitation (ChIP) assay. The maximal basal and HGF-induced
      promoter activity for the PDGFA gene existed within -630 bp of the promoter
      region, and overexpression of Egr-1 significantly increased such activity.
      Consistent with this, expression of PDGFA and VEGF but not IL-8 showed
      corresponding differences with Egr-1 expression in HNSCC tumor specimens and were
      strongly suppressed by transfection of Egr-1-antisense or small interference RNA
      (siRNA) oligonucleotides. HGF-induced expression of Egr-1, PDGFA, and VEGF was
      suppressed by pharmacologic and siRNA inhibitors of mitogen-activated protein
      kinase kinase 1/2 (MEK1/2) and protein kinase C (PKC) pathways. We conclude that
      the HGF-induced activation of transcription factor Egr-1 by MEK1/2- and PKC
      dependent mechanisms differentially contributes to expression of PDGF and VEGF,
      which are important angiogenesis factors and targets for HNSCC therapy.

PMID- 16103055
TI  - Epigenetic inactivation of SFRP genes and TP53 alteration act jointly as markers
      of invasive bladder cancer.
AB  - In the United States each year, almost 13,000 deaths are attributable to bladder
      cancer, with the majority of these deaths related to higher stage, muscle
      invasive solid tumors. Epigenetic silencing of the secreted frizzled receptor
      proteins (SFRP), antagonists of the WNT pathway, leads to constitutive WNT
      signaling, altering cell morphology and motility. Identifying alterations in this
      pathway in bladder cancer may prove useful for defining the invasive phenotype
      and provide targets for guiding therapy. Using a population-based study of
      bladder cancer (n = 355), we examined epigenetic alterations, specifically gene
      promoter hypermethylation, of four SFRP genes in addition to immunohistochemical
      staining of TP53, which has been previously shown to be a predictor of invasive
      disease. We observed a significant linear trend (P < 0.0004) in the magnitude of
      the risk of invasive disease with the number of SFRP genes methylated. Both TP53
      alteration and SFRP gene methylation showed significant independent associations
      with invasive bladder cancer. Strikingly, in examining the joint effect of these
      alterations, we observed a >30-fold risk of invasive disease for patients with
      both altered SFRP gene methylation and intense TP53 staining (odds ratio, 32.1; P
      < 10(-13)). Overall patient survival was significantly poorer in patients with
      any SFRP genes methylated (P < 0.0003) and in proportional hazards modeling,
      patients with methylation of any SFRP gene had significantly poorer overall
      survival (hazard ratio, 1.78; P < 0.02) controlled for TP53 staining intensity
      and other survival-associated factors. Classifying tumors based on SFRP
      methylation status and TP53 protein staining intensity may be a clinically
      powerful predictor of invasive, deadly disease.

PMID- 16103056
TI  - Characterization of DNA demethylation effects induced by 5-Aza-2'-deoxycytidine
      in patients with myelodysplastic syndrome.
AB  - Azanucleoside drugs such as 5-azacytidine (Vidaza) and 5-aza-2'-deoxycytidine
      (decitabine, Dacogen) function as DNA methyltransferase inhibitors in vitro and
      represent promising new drugs for the treatment of myelodysplastic syndrome (MDS)
      and acute myeloid leukemia. In this study, we aimed to determine the effect of
      decitabine on the genomic methylation level in MDS patients. Comparison of
      different assays established micellar electrokinetic chromatography as a reliable
      method for the analysis of genomic methylation levels. When used for the
      determination of DNA methylation levels in bone marrow DNA from MDS patients
      during various time points of decitabine treatment, the results revealed a
      significant (up to 70%) demethylation in five of seven patients. Interestingly,
      genome-wide demethylation appeared after karyotype normalization, which suggests
      demethylation of nonclonal cells. Drug-induced demethylation dynamics were also
      confirmed by bisulfite sequencing of pericentromeric satellite elements. Our
      results are the first to show a genome-wide demethylating activity of decitabine
      in tumor material. In addition, our data uncovers novel targets of decitabine
      mediated demethylation that are important for the refinement of treatment
      schedules with demethylating drugs.

PMID- 16103057
TI  - Heterozygous ATR mutations in mismatch repair-deficient cancer cells have
      functional significance.
AB  - ATR (ataxia telangiectasia and Rad3-related) function is necessary for the proper
      response to commonly used chemotherapeutic agents. Heterozygous truncating
      mutations in exon 10 of the ATR gene have been described in numerous cancers
      exhibiting microsatellite instability. We show that truncating mutations of ATR
      are capable of acting in a dominant-negative manner to abrogate ATR-dependent
      Chk1 phosphorylation and cell-cycle arrests after DNA damage. In addition,
      endometrial cell lines harboring ATR mutations are defective for ATR-dependent
      responses. These findings imply that ATR mutations play an important role in the
      development and clinical behavior of a subset of microsatellite instability
      positive endometrial, colon, and stomach cancers.

PMID- 16103058
TI  - An alternative inhibitor overcomes resistance caused by a mutation of the
      epidermal growth factor receptor.
AB  - Mutations of the epidermal growth factor receptor (EGFR) gene have been
      identified in non-small cell lung cancer specimens from patients responding to
      anilinoquinazoline EGFR inhibitors. However, clinical resistance to EGFR
      inhibitor therapy is commonly observed. Previously, we showed that such
      resistance can be caused by a second mutation of the EGFR gene, leading to a
      T790M amino acid change in the EGFR tyrosine kinase domain and also found that CL
      387,785, a specific and irreversible anilinoquinazoline EGFR inhibitor, was able
      to overcome this resistance on the biochemical level. Here, we present the
      successful establishment of a stable Ba/F3 cell line model system for the study
      of oncogenic EGFR signaling and the functional consequences of the EGFR T790M
      resistance mutation. We show the ability of gefitinib to induce growth arrest and
      apoptosis in cells transfected with wild-type or L858R EGFR, whereas the T790M
      mutation leads to high-level functional resistance against gefitinib and
      erlotinib. In addition, CL-387,785 is able to overcome resistance caused by the
      T790M mutation on a functional level, correlating with effective inhibition of
      downstream signaling pathways. Similar data was also obtained with the use of the
      gefitinib-resistant H1975 lung cancer cell line. The systems established by us
      should prove useful for the large-scale screening of alternative EGFR inhibitor
      compounds against the T790M or other EGFR mutations. These data also support the
      notion that clinical investigations of compounds similar to CL-387,785 may be
      useful as a treatment strategy for patients with resistance to EGFR inhibitor
      therapy caused by the T790M mutation.

PMID- 16103059
TI  - Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung
      cancer.
AB  - We investigated gene expression profiles of non-small cell lung carcinomas
      (NSCLC) to screen candidate molecules that might be useful as diagnostic markers
      or for development of novel molecular-targeting therapies. Here we report
      evidence that a member of the armadillo protein family, plakophilin 3 (PKP3), is
      a potential molecular target for treatment of lung cancers and might also serve
      as a prognostic indicator. We documented elevated expression of PKP3 in the great
      majority of NSCLC samples examined. Treatment of NSCLC cells with small
      interfering RNAs of PKP3 suppressed growth of the cancer cells; on the other
      hand, induction of exogenous expression of PKP3 conferred growth-promoting
      activity on COS-7 cells and enhanced their mobility in vitro. To investigate its
      function, we searched for PKP3-interacting proteins and identified dynamin 1
      like, which was also activated in NSCLC. In addition, a high level of PKP3
      expression was associated with poor survival as well as disease stage and node
      status for patients with lung adenocarcinoma, suggesting an important role of the
      protein in development and progression of this disease. As our data imply that up
      regulation of PKP3 is a frequent and important feature of lung carcinogenesis, we
      suggest that targeting the PKP3 molecule might hold promise for development of a
      new therapeutic and diagnostic strategy for clinical management of lung cancers.

PMID- 16103060
TI  - RalA and RalB: antagonistic relatives in cancer cell migration.
AB  - The Ral family of small G proteins has been implicated in tumorigenesis,
      invasion, and metastasis. However, little emphasis has been placed on clarifying
      the individual roles of the two Ral proteins, RalA and RalB, in these processes
      in view of their high sequence homology. Here we analyze the separate
      contributions of RalA and RalB in regulating cell migration, a necessary
      component of the invasive phenotype, in two human cancer cell lines; UMUC-3, a
      bladder carcinoma line, and the prostate carcinoma line, DU145. Although
      inhibiting RalA protein expression by approximately 80% with two different small
      interfering RNA duplexes had no effect on migration, inhibiting RalB expression
      to the same extent with two different duplexes resulted in a marked reduction in
      migration. Inhibiting RalB expression did trigger a significant loss of actin
      cytoskeleton fibers in UMUC-3 that was not seen with inhibition of RalA
      expression. Interestingly, simultaneous inhibition of RalA and RalB expression
      had no effect on migration. However, dual inhibition of RalA and RalB expression
      in UMUC-3 did result in an almost total loss of actin fibers as well as a
      reduction in proliferation, particularly in reduced serum conditions. These
      results suggest that RalA and RalB have different roles in cell migration and
      that they may in fact act as antagonists with regard to this phenotype. As
      further verification of this hypothesis, we found that expression of
      constitutively active RalA inhibited migration, whereas expression of
      constitutively active RalB stimulated migration, consistent with this model. In
      summary, we present the first demonstration that despite their significant
      sequence homology, RalA and RalB have nonoverlapping and opposing functions in
      cancer cell migration but overlapping functions in cell growth.

PMID- 16103061
TI  - Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor
      gene frequently inactivated in clinically aggressive meningioma.
AB  - Although meningiomas are common central nervous system tumors, little is known
      about the genetic events responsible for malignant progression. In this study, we
      employed gene expression profiling to identify transcripts whose expression was
      lost in anaplastic (WHO grade III) versus benign (WHO grade I) meningioma.
      Approximately 40% of genes down-regulated in anaplastic meningioma were localized
      to chromosomes 1p and 14q. One specific gene located at 14q11.2, NDRG2, was
      consistently down-regulated in grade III meningioma, a finding which we validated
      at both the transcript and protein levels in independent sets of clinically and
      pathologically diverse meningiomas. Loss of NDRG2 expression was also seen in a
      subset of lower-grade meningiomas, including atypical meningiomas (WHO grade II)
      with clinically aggressive behavior. Furthermore, we found that the loss of NDRG2
      expression was significantly associated with hypermethylation of the NDRG2
      promoter. Collectively, these data identify NDRG2 as the first specific candidate
      tumor suppressor gene on chromosome 14q that is inactivated during meningioma
      progression. In addition, these findings highlight the utility of combining
      genomic, epigenetic, and expression data to identify clinically significant tumor
      biomarkers, and suggest that NDRG2 expression will be a useful and functionally
      relevant biomarker to predict aggressive behavior in patients with meningioma.

PMID- 16103062
TI  - Expression profile of malignant and nonmalignant lesions of esophagus and
      stomach: differential activity of functional modules related to inflammation and
      lipid metabolism.
AB  - Adenocarcinomas of stomach and esophagus are frequently associated with preceding
      inflammatory alterations of the normal mucosa. Whereas intestinal metaplasia of
      the gastric mucosa is associated with higher risk of malignization, Barrett's
      disease is a risk factor for adenocarcinoma of the esophagus. Barrett's disease
      is characterized by the substitution of the squamous mucosa of the esophagus by a
      columnar tissue classified histopathologically as intestinal metaplasia. Using
      cDNA microarrays, we determined the expression profile of normal gastric and
      esophageal mucosa as well as intestinal metaplasia and adenocarcinomas from both
      organs. Data were explored to define functional alterations related to the
      transformation from squamous to columnar epithelium and the malignant
      transformation from intestinal metaplasia to adenocarcinomas. Based on their
      expression profile, adenocarcinomas of the esophagus showed stronger correlation
      with intestinal metaplasia of the stomach than with Barrett's mucosa. Second, we
      identified two functional modules, lipid metabolism and cytokine, as being
      altered with higher statistical significance. Whereas the lipid metabolism module
      is active in samples representing intestinal metaplasia and inactive in
      adenocarcinomas, the cytokine module is inactive in samples representing normal
      esophagus and esophagitis. Using the concept of relevance networks, we determined
      the changes in linear correlation of genes pertaining to these two functional
      modules. Exploitation of the data presented herein will help in the precise
      molecular characterization of adenocarcinoma from the distal esophagus, avoiding
      the topographical and descriptive classification that is currently adopted, and
      help with the proper management of patients with Barrett's disease.

PMID- 16103063
TI  - Mect1-Maml2 fusion oncogene linked to the aberrant activation of cyclic AMP/CREB
      regulated genes.
AB  - Malignant salivary gland tumors can arise from a t(11;19) translocation that
      fuses 42 residues from Mect1/Torc1, a cyclic AMP (cAMP)/cAMP-responsive element
      binding protein (CREB)-dependent transcriptional coactivator, with 982 residues
      from Maml2, a NOTCH receptor coactivator. To determine if the Mect1-Maml2 fusion
      oncogene mediates tumorigenicity by disrupting cAMP/CREB signaling, we have
      generated in-frame deletions within the CREB-binding domain of Mect1/Torc1 for
      testing transformation activity and have also developed a doxycycline-regulated
      Mect1-Maml2 mammalian expression vector for global gene expression profiling. We
      observed that small deletions within the CREB-binding domain completely abolished
      transforming activity in RK3E epithelial cells. Further, we have shown that the
      ectopic induction of Mect1-Maml2 in HeLa cells strongly activated the expression
      of a group of known cAMP/CREB-regulated genes. In addition, we detected candidate
      cAMP-responsive element sites within 100 nucleotides of the transcriptional start
      sites of other genes activated by Mect1-Maml2 expression. In contrast, we did not
      observe alterations of known Notch-regulated target genes in these expression
      array profile experiments. We validated the results by reverse transcription-PCR
      in transfected HeLa, RK3E, and H2009 lung tumor cells and in mucoepidermoid
      cancer cells that endogenously express the fusion oncopeptide. Whereas
      overexpression of components of the cAMP pathway has been associated with a
      subset of human carcinomas, these data provide a direct genetic link between
      deregulation of cAMP/CREB pathways and epithelial tumorigenesis and suggest
      future therapeutic strategies for this group of salivary gland tumors.

PMID- 16103064
TI  - Mechanistic analysis of the role of BLCA-4 in bladder cancer pathobiology.
AB  - Analysis of alterations in nuclear structure associated with bladder cancer has
      revealed specific changes associated with the disease. This includes the
      identification of six bladder cancer-specific proteins and the successful
      development of urine-based immunoassays for the detection of two of these
      biomarkers, BLCA-1 and BLCA-4. The purpose of this study is to examine the
      functional aspects of BLCA-4 and its potential role in bladder cancer
      pathobiology. Sequence analysis of BLCA-4 reveals that it is a member of the ETS
      transcription factor family and that it seems to associate with transcription
      factors. To examine the effects of this protein, the gene encoding BLCA-4 was
      stably transfected into human urothelial cells. BLCA-4 expression was confirmed
      by both PCR and Western blot analysis. BLCA-4 overexpressing clones exhibit a 4.3
      fold greater proliferation rate than vector only controls or untransfected cells.
      Microarray analysis comparing gene expression patterns between overexpressing
      clones and vector only controls revealed that numerous genes were up-regulated in
      cells that overexpress BLCA-4. Up-regulated genes included interleukin-1alpha (IL
      1alpha), IL-8, and thrombomodulin, and the protein expression of these genes was
      confirmed by immunoblots. This information has provided a potential model of BLCA
      4 action. Overexpression of BLCA-4 seems to increase the growth rate in cells and
      also causes cells to express a more tumorigenic phenotype.

PMID- 16103066
TI  - Suppression of p53 by Notch in lymphomagenesis: implications for initiation and
      regression.
AB  - Aberrant Notch signaling contributes to more than half of all human T-cell
      leukemias, and accumulating evidence indicates Notch involvement in other human
      neoplasms. We developed a tetracycline-inducible mouse model (Top-Notch(ic)) to
      examine the genetic interactions underlying the development of Notch-induced
      neoplastic disease. Using this model, we show that Notch suppresses p53 in
      lymphomagenesis through repression of the ARF-mdm2-p53 tumor surveillance
      network. Attenuation of Notch expression resulted in a dramatic increase in p53
      levels that led to tumor regression by an apoptotic program. This shows that
      continued Notch activity is required to maintain the disease state. However, all
      tumors relapsed with rapid kinetics, most of which, by reactivation of Notch
      expression. Furthermore, by directly inhibiting the mdm2-p53 interaction by using
      either ionizing radiation or the novel small molecule therapeutic Nutlin, p53 can
      be activated and cause tumor cell death, even in the presence of sustained Notch
      activity. Therefore, it is the suppression of p53 that provides the Achilles heel
      for Notch-induced tumors, as activation of p53 in the presence of Notch signaling
      drives tumor regression. Our study provides proof-of-principle for the rational
      targeting of therapeutics against the mdm2-p53 pathway in Notch-induced
      neoplasms. Furthermore, we propose that suppression of p53 by Notch is a key
      mechanism underlying the initiation of T-cell lymphoma.

PMID- 16103065
TI  - OLIG2 (BHLHB1), a bHLH transcription factor, contributes to leukemogenesis in
      concert with LMO1.
AB  - OLIG2 (originally designated BHLHB1) encodes a transcription factor that contains
      the basic helix-loop-helix motif. Although expression of OLIG2 is normally
      restricted to neural tissues, overexpression of OLIG2 has been shown in patients
      with precursor T-cell lymphoblastic lymphoma/leukemia (pre-T LBL). In the current
      study, we found that overexpression of OLIG2 was not only found in
      oligodendroglioma samples and normal neural tissue but also in a wide spectrum of
      malignant cell lines including leukemia, non-small cell lung carcinoma, melanoma,
      and breast cancer cell lines. To investigate whether enforced expression of OLIG2
      is oncogenic, we generated transgenic mice that overexpressed OLIG2 in the
      thymus. Ectopic OLIG2 expression in the thymus was only weakly oncogenic as only
      2 of 85 mice developed pre-T LBL. However, almost 60% of transgenic mice that
      overexpressed both OLIG2 and LMO1 developed pre-T LBL with large thymic tumor
      masses. Gene expression profiling of thymic tumors that developed in OLIG2/LMO1
      mice revealed up-regulation of Notch1 as well as Deltex1 (Dtx1) and pre T-cell
      antigen receptor alpha (Ptcra), two genes that are considered to be downstream of
      Notch1. Of note, we found mutations in the Notch1 heterodimerization or proline-,
      glutamic acid-, serine-, and threonine-rich domain in three of six primary thymic
      tumors. In addition, growth of leukemic cell lines established from OLIG2/LMO1
      transgenic mice was suppressed by a gamma-secretase inhibitor, suggesting that
      Notch1 up-regulation is important for the proliferation of OLIG2-LMO1 leukemic
      cells.

PMID- 16103067
TI  - Prediction of radiation sensitivity using a gene expression classifier.
AB  - The development of a successful radiation sensitivity predictive assay has been a
      major goal of radiation biology for several decades. We have developed a
      radiation classifier that predicts the inherent radiosensitivity of tumor cell
      lines as measured by survival fraction at 2 Gy (SF2), based on gene expression
      profiles obtained from the literature. Our classifier correctly predicts the SF2
      value in 22 of 35 cell lines from the National Cancer Institute panel of 60, a
      result significantly different from chance (P = 0.0002). In our approach, we
      treat radiation sensitivity as a continuous variable, significance analysis of
      microarrays is used for gene selection, and a multivariate linear regression
      model is used for radiosensitivity prediction. The gene selection step identified
      three novel genes (RbAp48, RGS19, and R5PIA) of which expression values are
      correlated with radiation sensitivity. Gene expression was confirmed by
      quantitative real-time PCR. To biologically validate our classifier, we
      transfected RbAp48 into three cancer cell lines (HS-578T, MALME-3M, and MDA-MB
      231). RbAp48 overexpression induced radiosensitization (1.5- to 2-fold) when
      compared with mock-transfected cell lines. Furthermore, we show that HS-578T
      RbAp48 overexpressors have a higher proportion of cells in G2-M (27% versus 5%),
      the radiosensitive phase of the cell cycle. Finally, RbAp48 overexpression is
      correlated with dephosphorylation of Akt, suggesting that RbAp48 may be exerting
      its effect by antagonizing the Ras pathway. The implications of our findings are
      significant. We establish that radiation sensitivity can be predicted based on
      gene expression profiles and we introduce a genomic approach to the
      identification of novel molecular markers of radiation sensitivity.

PMID- 16103068
TI  - Homeobox D10 induces phenotypic reversion of breast tumor cells in a three
      dimensional culture model.
AB  - Homeobox (Hox) genes are master regulatory genes that direct organogenesis and
      maintain differentiated tissue function. We previously reported that HoxD10 helps
      to maintain a quiescent, differentiated phenotype in endothelial cells by
      suppressing expression of genes involved in remodeling the extracellular matrix
      and cell migration. Here we investigated whether HoxD10 could also promote or
      maintain a differentiated phenotype in epithelial cells. We observed that HoxD10
      expression is progressively reduced in epithelial cells as malignancy increases
      in both breast and endometrial tumors. Retroviral gene transfer to restore
      expression of HoxD10 in the malignant breast tumor cells MDA-MB-231 significantly
      impaired migration, and when these cells were cultured in a three-dimensional
      laminin-rich basement membrane (3DlrBM) model, they formed polarized, acinar
      structures. This phenotypic reversion was accompanied by decreased alpha3
      integrin expression and reduced proliferation. Importantly, expression of HoxD10
      in the MDA-MB-231 cells inhibited their ability to form tumors in mouse
      xenografts. Taken together, our results suggest that HoxD10 has tumor-suppressive
      functions for mammary epithelial cells.

PMID- 16103069
TI  - Recombinant human erythropoietin alpha targets intratumoral blood vessels,
      improving chemotherapy in human xenograft models.
AB  - Recombinant human erythropoietin (rHuEPO) is widely used for correction of
      hemoglobin level in cancer patients. However, apart from hematopoiesis, rHuEPO
      reportedly has an effect on endothelial cells. We describe here how rHuEPOalpha
      can modulate tumor vasculature in human squamous cell (A431) and colorectal
      carcinoma (HT25) xenograft models. In vivo rHuEPO treatment of xenografts at
      human-equivalent dose significantly increased the proliferation index of the
      tumor-associated endothelial cells and the size of CD31-positive intratumoral
      blood vessels, whereas the pericyte coverage became fragmented. Moreover, rHuEPO
      administration resulted in decreased expression of vascular endothelial growth
      factor both by cancer cells and tumor stroma, measured by quantitative PCR. Due
      to the morphologic alterations in tumoral microvessels, DNA-binding agents
      (Hoechst and Doxorubicin) labeled significantly larger areas in the tumor mass.
      Furthermore, rHuEPO treatment led to a significantly improved efficacy of 5
      fluorouracil (5-FU) chemotherapy in the case of both tumor xenografts. Meanwhile,
      rHuEPO had no effect on the in vitro proliferation of erythropoietin receptor
      positive tumor cells, and did not interfere with the effects of 5-FU either.
      These data reveal a new effect of rHuEPO administration: remodeling tumoral
      microvessels, suppressing vascular endothelial growth factor expression, thereby
      augmenting antitumor effects of a cancer drug, 5-FU, even in erythropoietin
      receptor-positive human cancer xenografts.

PMID- 16103070
TI  - Combined immunostimulation and conditional cytotoxic gene therapy provide long
      term survival in a large glioma model.
AB  - In spite of preclinical efficacy and recent randomized, controlled studies with
      adenoviral vectors expressing herpes simplex virus-1 thymidine kinase (HSV1-TK)
      showing statistically significant increases in survival, most clinical trials
      using single therapies have failed to provide major therapeutic breakthroughs.
      Because glioma is a disease with dismal prognosis and rapid progression, it is an
      attractive target for gene therapy. Preclinical models using microscopic brain
      tumor models (e.g., < or =0.3 mm3) may not reflect the pathophysiology and
      progression of large human tumors. To overcome some of these limitations, we
      developed a syngeneic large brain tumor model. In this model, administration of
      single therapeutic modalities, either conditional cytotoxicity or
      immunostimulation, fail. However, when various immunostimulatory therapies were
      delivered in combination with conditional cytotoxicity (HSV1-TK), only the
      combined delivery of fms-like tyrosine kinase ligand (Flt3L) and HSV1-TK
      significantly prolonged the survival of large tumor-bearing animals (> or =80%; P
      < or = 0.005). When either macrophages or CD4+ cells were depleted before
      administration of viral therapy, TK + Flt3L therapy failed to prolong survival.
      Meanwhile, depletion of CD8+ cells or natural killer cells did not affect TK +
      Flt3L efficacy. Spinal cord of animals surviving 6 months after TK + Flt3L were
      evaluated for the presence of autoimmune lesions. Whereas macrophages were
      present within the corticospinal tract and low levels of T-cell infiltration were
      detected, these effects are not indicative of an overt autoimmune disorder. We
      propose that combined Flt3L and HSV1-TK adenoviral-mediated gene therapy may
      provide an effective antiglioma treatment with increased efficacy in clinical
      trials of glioma.

PMID- 16103071
TI  - Caspase-1 is a direct target gene of ETS1 and plays a role in ETS1-induced
      apoptosis.
AB  - ETS1, the founding member of Ets transcriptional factor family, plays an
      important role in cell proliferation, differentiation, lymphoid cell development,
      transformation, angiogenesis, and apoptosis. Previous work has shown that ETS1
      represses tumorigenicity of colon carcinoma cells in vivo, and that the p42-ETS1
      protein bypasses a defect in apoptosis in colon carcinoma cells through the up
      regulation of caspase-1 expression. In this report, we show that expression of
      p42-ETS1 inhibits tumorigenicity of colon cancer DLD-1 cells through induction of
      apoptosis in vivo. In support of the hypothesis that caspase-1 might be a target
      involved in the sensitization of DLD-1 cells to Fas-induced apoptosis by ETS1,
      overexpression of caspase-1 bypasses Fas-induced apoptosis in these cells as
      well. Furthermore, ETS1-mediated apoptosis was observed in MOP8 cells, a
      transformed mouse NIH3T3 cell line. To determine whether ETS1 activates the
      transcription of caspase-1, luciferase reporters driven by the wild-type and
      mutant caspase-1 promoters were generated. Both p51-ETS1 and p42-ETS1
      transactivated the caspase-1 transcription and a functional Ets binding site is
      identified in the caspase-1 promoter. Wild-type caspase-1 promoter (pGL3-ICE) was
      strongly transactivated by ETS1 and this transactivation was dramatically
      diminished by the mutation of the potential Ets binding site (-525 bp). In
      addition, electrophoretic mobility shift assay and chromatin immunoprecipitation
      assay showed complex formation between this binding site and ETS1 proteins. Taken
      together, ETS1 transcriptionally induces the expression of caspase-1; as such,
      the regulatory control of caspase-1 expression by ETS1 may underlie the apoptotic
      susceptibility modulated by ETS1 in specific tumor cells.

PMID- 16103072
TI  - Expression and activity of SRC regulate interleukin-8 expression in pancreatic
      adenocarcinoma cells: implications for angiogenesis.
AB  - Interleukin-8 (IL-8) is an angiogenic factor that promotes growth of pancreatic
      tumors. The purpose of this study was to determine if c-Src, a protein tyrosine
      kinase frequently overexpressed in pancreatic cancer, regulated IL-8 expression
      and to elucidate the Src-mediated signaling pathways that contribute to
      angiogenesis in pancreatic adenocarcinoma cells. In a panel of pancreatic cancer
      cell lines, expression of total and activated Src correlated with IL-8
      production. Furthermore, ectopic expression of activated Src in PANC-1 cells with
      low endogenous Src activity significantly increased IL-8 production (P < 0.005).
      In contrast, pharmacologic inhibition of endogenous c-Src kinase activity or
      small interfering RNA-mediated "knockdown" of c-Src expression in L3.6pl cells
      with high Src expression and activity caused significant decreases in IL-8
      production (P < 0.005). Inhibition of c-Src activity resulted in decreased
      phosphorylation of Akt, p38, and extracellular signal-regulated kinase (Erk)-1/2.
      Significant (P < 0.005) dose-dependent decreases were observed in IL-8 expression
      by inhibiting Src-dependent signaling molecules Erk-1/2 and p38 but not
      phosphatidylinositol 3-kinase. To assess the relevance of Src inhibition to
      angiogenesis, in vivo gelfoam assays were done. Robust infiltration of vessels
      was observed in gelfoam saturated with conditioned medium from pancreatic
      carcinoma cells. This angiogenesis was nearly abrogated in gelfoams saturated
      with conditioned medium from cells treated with the Src family kinase inhibitor,
      PP2 (P < 0.001). Thus, c-Src regulates critical "downstream" signaling pathways
      that contribute to expression of IL-8 in human pancreatic tumor cells, suggesting
      c-Src may be a target for therapeutic intervention in pancreatic adenocarcinoma.

PMID- 16103073
TI  - Mouse mammary tumor virus Env-derived peptide associates with nucleolar targets
      in lymphoma, mammary carcinoma, and human breast cancer.
AB  - We have previously shown that the leader peptide (p14) of the Env-precursor of
      mouse mammary tumor virus is translocated into the nucleoli of murine T cell
      lymphomas that harbor this virus. Using a polyclonal antibody against recombinant
      p14, we show here that p14 is also localized to the nucleoli of murine mammary
      carcinomas and some human breast cancer samples. Affinity purification studies
      define a number of proteins, mostly nucleolar, that bind p14. Taken together,
      these findings point towards a more general involvement of p14 in lymphomagenesis
      and mammary carcinogenesis.

PMID- 16103074
TI  - Oncogenic tyrosine kinase of malignant hemopathy targets the centrosome.
AB  - Myeloproliferative disorders (MPD) are malignant diseases of hematopoietic
      progenitor cells. Many MPDs result from a chromosomal translocation that creates
      a fusion gene encoding a chimeric kinase. The fibroblast growth factor receptor 1
      (FGFR1)-MPD is characterized by the fusion of the FGFR1 kinase with various
      partners, including FOP. We show here that both normal FOP and FOP-FGFR1 fusion
      kinase localize to the centrosome. The fusion kinase encounters substrates at the
      centrosome where it induces strong phosphorylation on tyrosine residues.
      Treatment with FGFR1 kinase inhibitor SU5402 abolishes FOP-FGFR1-induced
      centrosomal phosphorylation and suppresses the proliferative and survival
      potentials of FOP-FGFR1 Ba/F3 cells. We further show that FOP-FGFR1 allows cells
      to overcome G1 arrest. Therefore, the FOP-FGFR1 fusion kinase targets the
      centrosome, activates signaling pathways at this organelle, and sustains
      continuous entry in the cell cycle. This could represent a potential new
      mechanism of oncogenic transformation occurring specifically at the centrosome.

PMID- 16103075
TI  - Platelet-derived growth factor-AA is an essential and autocrine regulator of
      vascular endothelial growth factor expression in non-small cell lung carcinomas.
AB  - It is widely accepted that angiogenesis is required for tumor progression.
      Vascular endothelial growth factor (VEGF) is a key molecule for tumor
      angiogenesis; however, its expressional regulation is not well understood during
      all stages of tumorigenesis. Using cell lines and surgical specimens of human non
      small cell lung cancers (NSCLCs), we here show that platelet-derived growth
      factor-AA (PDGF-AA) is an essential autocrine regulator for VEGF expression. To
      directly assess the expression of PDGF-AA-dependent VEGF and its roles in
      tumorigenesis, we stably transfected established cell lines with their antisense
      genes. In addition, the levels of PDGF-AA and VEGF expression in surgical
      sections were measured and compared with clinicopathologic findings such as tumor
      size and patient prognosis. PDGF-AA tightly regulated VEGF expression and had a
      greater effect on tumor size and patient prognosis than did VEGF in both cell
      lines and surgical sections. PDGF-AA expression was not seen in the atypical
      adenomatous hyperplasia at all, whereas VEGF was occasionally seen. Furthermore,
      the frequency of VEGF expression was higher in advanced NSCLCs than in
      precancerous lesions, which was tightly correspondent to the results for PDGF-AA.
      These results indicate that PDGF-AA is an important regulator of the frequency
      and level of VEGF expression during the transition from a precancerous lesion to
      advanced cancer. The PDGF-AA/VEGF axis, therefore, may be a ubiquitous autocrine
      system for enhancing angiogenic signals, and PDGF-AA, and its related pathways
      could be a more efficient target of antiangiogenic therapy for cancers than VEGF
      and its pathways.

PMID- 16103076
TI  - Evaluating hypoxia-inducible factor-1alpha as a cancer therapeutic target via
      inducible RNA interference in vivo.
AB  - Validating potential targets is an important step in the drug discovery process.
      In this study, we tested the feasibility of using inducible RNA interference
      (RNAi) in vivo to obtain an unbiased evaluation on the efficacy of inhibiting
      hypoxia-inducible factor-1alpha (HIF-1alpha) in established tumors. We showed
      that HIF-1alpha inhibition resulted in transient tumor stasis or tumor
      regression, and inhibiting HIF-1alpha in early-stage tumors was found to be more
      efficacious than inhibiting HIF-1alpha in more established tumors. A differential
      requirement of HIF-1alpha for tumor growth was also observed among different
      tumor types. Examination of tumors resistant to HIF-1alpha inhibition suggested
      that the resistance might result from a less hypoxic tumor environment and the
      level of HIF-1alpha expression in tumors may be a useful marker for predicting
      tumor response to HIF-1 inhibition. This study shows that inducible RNAi is a
      versatile tool for evaluating cancer targets in vivo. In addition to broad
      implications on in vivo validation of cancer targets, results from this study
      will also be instructive for practical applications of HIF-1-based cancer
      therapeutics.

PMID- 16103077
TI  - Reduced expression of hypoxia-inducible factor-1alpha in perinecrotic regions of
      solid tumors.
AB  - Hypoxia that develops in solid tumors stabilizes the hypoxia-inducible factor
      1alpha (HIF-1alpha) subunit of the HIF-1 transcription factor, leading to up
      regulation of dozens of hypoxia-regulated genes that increase glycolysis and
      oxygen delivery. HIF-1alpha and its downstream target gene CA9 have both been
      used as surrogate hypoxia markers, and, in general, high expression predicts for
      a poor response to treatment. Combinations of hypoxia markers offer the
      opportunity to measure changes in tumor oxygenation that may be relevant to tumor
      response to treatment. We compared the degree of colocalization of two endogenous
      markers for hypoxia, HIF-1alpha and carbonic anhydrase IX (CAIX), with a chemical
      marker for hypoxia, pimonidazole. Unexpectedly, expression of HIF-1alpha was
      reduced in the most hypoxic regions that border necrosis in xenograft tumors
      composed of SiHa cervical carcinoma, WiDr colon carcinoma, or M006 astrocytoma
      cells. Similar results were obtained for samples from three cervical cancer
      biopsies. However, CAIX was present in these perinecrotic cells that were also
      capable of metabolizing and binding a chemical marker for hypoxia, pimonidazole.
      In vitro experiments using tumor cells and tumor cubes incubated under anoxic
      conditions indicated that nutrient deprivation seems to be largely responsible
      for the lack of HIF-1alpha expression in perinecrotic regions. The half-life of
      CAIX was sufficiently long that, once formed, it remained for days in the absence
      of continued HIF-1alpha expression. These results have implications for the use
      of HIF-1alpha as an indicator of tumor hypoxia and aggressiveness as well as
      development of hypoxia-directed antitumor therapies based on the expression of
      HIF-1alpha.

PMID- 16103078
TI  - A hypoxia-driven vascular endothelial growth factor/Flt1 autocrine loop interacts
      with hypoxia-inducible factor-1alpha through mitogen-activated protein
      kinase/extracellular signal-regulated kinase 1/2 pathway in neuroblastoma.
AB  - Flt1, an "fms-like tyrosine kinase" receptor, has been suggested to play an
      active role in vascular endothelial growth factor (VEGF)-mediated autocrine
      signaling of tumor growth and angiogenesis. Here, we used a neuroblastoma model
      to investigate the role of VEGF/Flt1 signaling in hypoxia-mediated tumor cell
      survival, drug resistance, and in vivo angiogenesis. SK-N-BE2, a highly malignant
      neuroblastoma cell line resistant to hypoxia-induced apoptosis expresses active
      Flt1 but lacks VEGFR2 expression. We found that 24-hour hypoxia (<0.1% O2) alone
      (no serum deprivation) showed sustained activation of extracellular signal
      regulated kinase 1/2 (ERK1/2) associated with bcl-2 up-regulation and resistance
      to etoposide-induced (5 mumol/L) apoptosis. Treatment with anti-VEGF and anti
      Flt1 antibodies inhibited ERK1/2 activation, down-regulated bcl-2, and reversed
      the hypoxia-mediated drug resistance to etoposide. Similar results were obtained
      with U0126 and ursolic acid, specific and nonspecific inhibitors of ERK1/2,
      respectively. We confirmed the protective role of Flt1 receptor by small
      interfering RNA knockout and Flt1 overexpression studies. Subsequently, we found
      that inhibition of VEGF/Flt1 autocrine signaling led to reduced hypoxia-inducible
      factor-1alpha (HIF-1alpha) phosphorylation. Furthermore, the reduced
      phosphorylation was associated with down-regulation of basic fibroblast growth
      factor, a downstream target of the HIF-1alpha and VEGF pathways. Our findings
      suggested an expanded autocrine loop between VEGF/Flt1 signaling and HIF-1alpha.
      We investigated the angiogenic activity of the loop in an in vivo Matrigel plug
      assay. The hypoxia-treated conditioned medium induced a strong angiogenic
      response, as well as the cooption of surrounding vessels into the plugs; ursolic
      acid inhibited the angiogenesis process. We also found that three other Flt1
      expressing neuroblastoma cell lines show hypoxia-mediated drug resistance to
      etoposide, melphalan, doxorubicin, and cyclophosphamide. Taken together, we
      conclude that a hypoxia-driven VEGF/Flt1 autocrine loop interacts with HIF-1alpha
      through a mitogen-activated protein kinase/ERK1/2 pathway in neuroblastoma. The
      interaction, in the form of an autocrine loop, is required for the hypoxia-driven
      cell survival, drug resistance, and angiogenesis in neuroblastoma.

PMID- 16103079
TI  - 15(S)-hydroxyeicosatetraenoic acid induces angiogenesis via activation of PI3K
      Akt-mTOR-S6K1 signaling.
AB  - To determine whether the lipoxygenase metabolites of arachidonic acid, 5(S)-,
      12(S)-, and 15(S)-hydroxyeicosatetraenoic acids [5(S)-HETE, 12(S)-HETE, and 15(S)
      HETE, respectively] are angiogenic, we have studied their effects on human dermal
      microvascular endothelial cell (HDMVEC) tube formation and migration. All three
      HETEs stimulated HDMVEC tube formation and migration. Because 15(S)-HETE was
      found to be more potent than 5(S)-HETE and 12(S)-HETE in HDMVEC tube formation,
      we next focused on elucidation of the signaling mechanisms underlying its
      angiogenic activity. 15(S)-HETE stimulated Akt and S6K1 phosphorylation in HDMVEC
      in a time-dependent manner. Wortmannin and LY294002, two specific inhibitors of
      phosphatidylinositol 3-kinase (PI3K), blocked both Akt and S6K1 phosphorylation,
      whereas rapamycin, a specific inhibitor of Akt downstream effector, mammalian
      target of rapamycin (mTOR), suppressed only S6K1 phosphorylation induced by 15(S)
      HETE suggesting that this eicosanoid activates the PI3K-Akt-mTOR-S6K1 signaling
      in HDMVEC. Wortmannin, LY294002, and rapamycin also inhibited 15(S)-HETE-induced
      HDMVEC tube formation and migration. In addition, all three HETEs stimulated
      angiogenesis as measured by in vivo Matrigel plug assay with 15(S)-HETE being
      more potent. Pharmacologic inhibition of PI3K-Akt-mTOR-S6K1 signaling completely
      suppressed 15(S)-HETE-induced in vivo angiogenesis. Consistent with these
      observations, adenoviral-mediated expression of dominant-negative Akt also
      blocked 15(S)-HETE-induced HDMVEC tube formation and migration and in vivo
      angiogenesis. Together, these results show for the first time that 15(S)-HETE
      stimulates angiogenesis via activation of PI3K-Akt-mTOR-S6K1 signaling.

PMID- 16103080
TI  - Galectin-3 regulates a molecular switch from N-Ras to K-Ras usage in human breast
      carcinoma cells.
AB  - Galectin-3 (Gal-3), a pleiotropic carbohydrate-binding protein, is a selective
      binding partner of activated K-Ras-GTP. Because both proteins are antiapoptotic
      and associated with cancer progression, we questioned the possible functional
      role of Gal-3 in K-Ras activation. We found that overexpression of Gal-3 in human
      breast cancer cells (BT-549/Gal-3) coincided with a significant increase in wild
      type (wt) K-Ras-GTP coupled with loss in wt N-Ras-GTP, whereas the nononcogenic
      Gal-3 mutant proteins [Gal-3(S6E) and Gal-3(G182A)] failed to induce the Ras
      isoform switch. Only wt Gal-3 protein coimmunoprecipitated and colocalized with
      oncogenic K-Ras, resulting in its activation with radical alterations in Ras
      signaling pathway, whereby the activation of AKT and Ral was suppressed and
      shifted to the activation of extracellular signal-regulated kinase (ERK).
      Specific inhibitors for Ras or mitogen-activated protein/ERK kinase
      (farnesylthiosalicylic acid and UO126, respectively) inhibited Gal-3-mediated
      apoptotic resistance and anchorage-independent growth functions. In conclusion,
      this study shows that Gal-3 confers on BT-549 human breast carcinoma cells
      several oncogenic functions by binding to and activation of wt K-Ras, suggesting
      that some of the molecular functions of Gal-3 are, at least in part, a result of
      K-Ras activation.

PMID- 16103081
TI  - Protein kinase C-epsilon regulates the apoptosis and survival of glioma cells.
AB  - In this study, we examined the role of protein kinase C (PKC)-epsilon in the
      apoptosis and survival of glioma cells using tumor necrosis factor-related
      apoptosis inducing ligand (TRAIL)-stimulated cells and silencing of PKCepsilon
      expression. Treatment of glioma cells with TRAIL induced activation, caspase
      dependent cleavage, and down-regulation of PKCepsilon within 3 to 5 hours of
      treatment. Overexpression of PKCepsilon inhibited the apoptosis induced by TRAIL,
      acting downstream of caspase 8 and upstream of Bid cleavage and cytochrome c
      release from the mitochondria. A caspase-resistant PKCepsilon mutant (D383A) was
      more protective than PKCepsilon, suggesting that both the cleavage of PKCepsilon
      and its down-regulation contributed to the apoptotic effect of TRAIL. To further
      study the role of PKCepsilon in glioma cell apoptosis, we employed short
      interfering RNAs directed against the mRNA of PKCepsilon and found that silencing
      of PKCepsilon expression induced apoptosis of various glioma cell lines and
      primary glioma cultures. To delineate the molecular mechanisms involved in the
      apoptosis induced by silencing of PKCepsilon, we examined the expression and
      phosphorylation of various apoptosis-related proteins. We found that knockdown of
      PKCepsilon did not affect the expression of Bcl2 and Bax or the phosphorylation
      and expression of Erk1/2, c-Jun-NH2-kinase, p38, or STAT, whereas it selectively
      reduced the expression of AKT. Similarly, TRAIL reduced the expression of AKT in
      glioma cells and this decrease was abolished in cells overexpressing PKCepsilon.
      Our results suggest that the cleavage of PKCepsilon and its down-regulation play
      important roles in the apoptotic effect of TRAIL. Moreover, PKCepsilon regulates
      AKT expression and is essential for the survival of glioma cells.

PMID- 16103082
TI  - PACE4 expression in mouse basal keratinocytes results in basement membrane
      disruption and acceleration of tumor progression.
AB  - Collagen type IV degradation results in disruption and breakdown of the normal
      basement membrane architecture, a key process in the initiation of tumor
      microinvasion into the connective tissue. PACE4, a proprotein convertase,
      activates membrane type matrix metalloproteinases (MT-MMPs) that in turn process
      collagenase type IV. Because PACE4 is overexpressed in skin carcinomas and in
      vitro overexpression of PACE4 resulted in enhanced invasiveness, we investigated
      whether or not in vivo PACE4 expression leads to the acquisition of invasiveness
      and increased tumorigenesis. Two transgenic mouse lines were designed by
      targeting PACE4 to the epidermal basal keratinocytes. Transgenic keratinocytes
      showed increased processing of MT1-MMP and MT2-MMP resulting in collagenase IV
      activation and collagen type IV degradation. Higher collagenolytic activity
      partially disrupted normal basement membrane architecture favoring epithelial
      endophytic growth into the dermis and accelerating invasion and metastasis after
      chemical carcinogenesis. PACE4 overexpression resulted in enhanced susceptibility
      to carcinogenesis and tumor progression pointing to a new target for blocking
      tumor cell invasiveness.

PMID- 16103083
TI  - Endothelin axis is a target of the lung metastasis suppressor gene RhoGDI2.
AB  - Half of patients treated for locally advanced bladder cancer relapse with often
      fatal metastatic disease to the lung. We have recently shown that reduced
      expression of the GDP dissociation inhibitor, RhoGDI2, is associated with
      decreased survival of patients with advanced bladder cancer. However, the
      effectors by which RhoGDI2 affects metastasis are unknown. Here we use DNA
      microarrays to identify genes suppressed by RhoGDI2 reconstitution in lung
      metastatic bladder cancer cell lines. We identify such RNAs and focus only on
      those that also increase with tumor stage in human bladder cancer samples to
      discover only clinically relevant targets of RhoGDI2. Levels of endothelin-1 (ET
      1), a potent vasoconstrictor, were affected by both RhoGDI2 reconstitution and
      tumor stage. To test the hypothesis that the endothelin axis is important in lung
      metastasis, lung metastatic bladder carcinoma cells were injected in mice treated
      with the endothelin receptor-specific antagonist, atrasentan, thereby blocking
      engagement of the up-regulated ET-1 ligand with its cognate receptor. Endothelin
      antagonism resulted in a dramatic reduction of lung metastases, similar to the
      effect of reexpressing RhoGDI2 in these metastatic cells. Taken together, these
      experiments show a novel approach of identifying therapeutic targets downstream
      of metastasis suppressor genes. The data also suggest that blockade of the ET-1
      axis may prevent lung metastasis, a new therapeutic concept that warrants
      clinical evaluation.

PMID- 16103084
TI  - B-cell receptor translocation to lipid rafts and associated signaling differ
      between prognostically important subgroups of chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease in which
      interaction of the malignant cells with antigen is thought to play a key role.
      Individual CLL-cell clones markedly differ in their ability to respond to B-cell
      receptor ligation, but the mechanism underlying the frequent hyporesponsiveness
      is incompletely understood. Our aim was to further clarify the extent and cause
      of the B-cell receptor signaling abnormality in CLL and to assign
      pathophysiologic relevance to the presence or absence of B-cell receptor
      responsiveness. We show that extracellular signal-regulated kinase-2
      phosphorylation, intracellular Ca2+ increases, CD79a phosphorylation, and
      translocation of the B-cell receptor to lipid rafts in response to ligation with
      anti-immunoglobulin M (as a surrogate for antigen) are features of CLL cells with
      relatively unmutated VH genes (<5% deviation from germ line) and a poor
      prognosis. B-cell receptor stimulation in these cases also promoted cell
      survival. In clones with mutated VH genes (>5% deviation from germ line), surface
      immunoglobulin M ligation failed to induce receptor translocation to rafts or to
      prolong cell survival. This failure of receptor translocation observed in mutated
      CLL cells was associated with the constitutive exclusion of the B-cell receptor
      from rafts by a mechanism involving src-dependent interactions between the B-cell
      receptor and the actin cytoskeleton. We conclude that exposure to antigen
      promotes the survival of unmutated CLL clones, contributing to the poor prognosis
      of this group. In contrast, hyporesponsive mutated CLL clones may have developed
      into a stage where continuous exposure to antigen results in relative tolerance
      to antigenic stimulation mediated by the exclusion of the B-cell receptor from
      lipid rafts.

PMID- 16103085
TI  - The FLT3 internal tandem duplication mutation prevents apoptosis in interleukin-3
      deprived BaF3 cells due to protein kinase A and ribosomal S6 kinase 1-mediated
      BAD phosphorylation at serine 112.
AB  - Internal tandem duplication (ITD) mutations in the FLT3 tyrosine kinase have been
      detected in approximately 20% of acute myeloid leukemia (AML) patients. Patients
      harboring FLT3/ITD mutations have a relatively poor prognosis. FLT3/ITD results
      in constitutive autophosphorylation of the receptor and factor-independent
      survival. Previous studies have shown that FLT3/ITD activates the signal
      transducers and activators of transcription 5 (STAT5), p42/p44 mitogen-activated
      protein kinase [MAPK; extracellular signal-regulated kinase (ERK) 1/2], and
      phosphatidylinositol 3-kinase/Akt pathways. We herein provide biochemical and
      biological evidence that ribosomal S6 kinase 1 (RSK1) and protein kinase A (PKA)
      are the two principal kinases that mediate the antiapoptotic function of FLT3/ITD
      via phosphorylation of BAD at Ser112. Inhibiting both MAPK kinase (MEK)/ERK and
      PKA pathways by a combination of U0126 (10 micromol/L) and H-89 (5 micromol/L)
      reduced most of BAD phosphorylation at Ser112 and induced apoptosis to a level
      comparable with that induced by FLT3 inhibitor AG1296 (5 micromol/L) in
      BaF3/FLT3/ITD cells. RNA interference of RSK1 or PKA catalytic subunit reduced
      BAD phosphorylation and induced apoptosis. The MEK inhibitor U0126 and/or the PKA
      inhibitor H-89 greatly enhanced the efficacy of the FLT3 inhibitor AG1296,
      suggesting that combining FLT3/ITD downstream pathway inhibition with FLT3
      inhibitors may be a viable therapeutic strategy for AML caused by a FLT3/ITD
      mutation.

PMID- 16103086
TI  - Tumor-associated antigen preferentially expressed antigen of melanoma (PRAME)
      induces caspase-independent cell death in vitro and reduces tumorigenicity in
      vivo.
AB  - Preferentially expressed antigen of melanoma (PRAME) is expressed in a wide
      variety of tumors, but in contrast with most other tumor associated antigens, it
      is also expressed in leukemias. The physiologic role of PRAME remains elusive.
      Interestingly, PRAME expression is correlated with a favorable prognosis in
      childhood acute leukemias. Moreover, a high expression of PRAME seems to be
      predominantly found in acute leukemias carrying a favorable prognosis. On these
      clinical observations, we assumed that PRAME could be involved in the regulation
      of cell death or cell cycle. In this study, we show that transient overexpression
      of PRAME induces a caspase-independent cell death in cultured cell lines (CHO-K1
      and HeLa). Cells stably transfected with PRAME also exhibit a decreased
      proliferation rate due, at least partially, to an elevated basal rate of cell
      death. Immunocytochemistry of a FLAG-tagged PRAME, in vivo imaging of an enhanced
      green fluorescent protein-tagged PRAME, and Western blotting after cell
      fractionation reveal a nuclear localization of the protein. Using a microarray
      based approach, we show that KG-1 leukemic cells stably transfected with PRAME
      present a significant decrease of expression of the heat-shock protein Hsp27, the
      cyclin-dependent kinase inhibitor p21, and the calcium-binding protein S100A4.
      The expression of these three proteins is known to inhibit apoptosis and has been
      associated with an unfavorable prognosis in a series of cancers. Finally,
      repression of PRAME expression by a short interfering RNA strategy increases
      tumorigenicity of K562 leukemic cells in nude mice. We suggest that all these
      observations might explain the favorable prognosis of the leukemias expressing
      high levels of PRAME.

PMID- 16103087
TI  - Deficiency of protein kinase Calpha in mice results in impairment of epidermal
      hyperplasia and enhancement of tumor formation in two-stage skin carcinogenesis.
AB  - We generated a mouse strain lacking protein kinase Calpha (PKCalpha) and
      evaluated the significance of the enzyme in epithelial hyperplasia and tumor
      formation. PKCalpha-deficient mice exhibited increased susceptibility to tumor
      formation in two-stage skin carcinogenesis by single application of 7,12
      dimethylbenz(a)anthracene (DMBA) for tumor initiation and repeated applications
      of 12-O-tetradecanoylphorbol-13-acetate (TPA) for tumor promotion. Tumor
      formation was not enhanced by DMBA or TPA treatment alone, suggesting that
      PKCalpha suppresses tumor promotion. However, the severity of epidermal
      hyperplasia induced by topical TPA treatment was markedly reduced. In mutant
      mice, the number of 5-bromo-2'-deoxyuridine-labeled epidermal basal keratinocytes
      increased 16 to 24 hours after topical TPA treatment as in the case of wild-type
      mice, but significantly decreased at 36 and 48 hours. Furthermore, the
      regenerating epithelium induced by skin wound significantly decreased in
      thickness but was not structurally impaired. The enhanced tumor formation may not
      be associated with epidermal hyperplasia. The induction levels of epidermal
      growth factor (EGF) receptor ligands, tumor growth factor alpha (TGF-alpha), and
      heparin-binding EGF-like growth factor, in the skin of mutant mice by TPA
      treatment were significantly lower than those in the skin of wild-type mice.
      PKCalpha may regulate the supply of these EGF receptor ligands in basal
      keratinocytes, resulting in a reduced epidermal hyperplasia severity in the
      mutant mice. We propose that PKCalpha positively regulates epidermal hyperplasia
      but negatively regulates tumor formation in two-stage skin carcinogenesis.

PMID- 16103088
TI  - Insulin-like growth factor binding protein-5 is a target of matrix
      metalloproteinase-7: implications for epithelial-mesenchymal signaling.
AB  - Matrix metalloproteinase-7 (MMP-7) is localized to epithelial cells and is up
      regulated in many cancers and in inflammation. We now report that MMP-7 targets a
      key mesenchymal cell type, the myofibroblast. Recombinant MMP-7 stimulated the
      proliferation and migration of human colonic myofibroblasts. These responses were
      partly attributable to activation of other MMPs, notably MMP-3 and MMP-8, and to
      stimulation of the mitogen-activated protein kinase and phosphatidylinositol 3
      kinase signaling pathways. Using a proteomic approach, we identified insulin-like
      growth factor binding protein-5 (IGFBP-5) as a previously unsuspected target of
      MMP-7 produced by colonic myofibroblasts. We present evidence that the MMP-7
      cleavage of IGFBP-5 liberates IGF-II that functions as an autocrine myofibroblast
      growth factor. Thus, MMP-7 may act as a signal from epithelial cells for local
      recruitment of myofibroblasts and stimulation of their proliferation. Similar
      effects of MMP-7 produced in epithelial tumors might account for the expansion of
      stroma through activation of myofibroblasts.

PMID- 16103089
TI  - Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer
      cell metastasis.
AB  - Skeletal metastases occur with high incidence in patients with breast cancer and
      cause long-term skeletal morbidity. Osteonectin (SPARC, BM-40) is a bone matrix
      factor that is an in vitro chemoattractant for breast and prostate cancer cells.
      Increased expression of osteonectin is found in malignant breast tumors. We
      infected MDA-231 breast cancer cells with an adenovirus expressing osteonectin to
      examine the role of osteonectin expression in breast cancer cells and its effect
      on metastasis, in particular to bone. Expression of osteonectin did not affect
      MDA-231 cell proliferation, apoptosis, migration, cell aggregation, or protease
      cleavage of collagen IV. However, in vitro invasion of these osteonectin-infected
      cells through Matrigel and colony formation on Matrigel was decreased.
      Interestingly, high osteonectin expression in MDA-231 cells inhibited metastasis
      in a dose-dependent manner to many different organs including bone. The reduction
      in metastasis may be due to decreased platelet-tumor cell aggregation, because
      exogenous osteonectin inhibited platelet aggregation in vitro and the high
      osteonectin expression in MDA-231 cells reduced tumor cell-induced
      thrombocytopenia in vivo compared with control-infected cells. These studies
      suggest that high endogenous expression of osteonectin in breast cancer cells may
      reduce metastasis via reduced invasive activity and reduced tumor cell-platelet
      aggregation.

PMID- 16103090
TI  - Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion
      and is associated with increased matrix metalloproteinase-2 activity.
AB  - Claudin proteins form a large family of integral membrane proteins crucial for
      tight junction formation and function. Our previous studies have revealed that
      claudin-3 and claudin-4 proteins are highly overexpressed in ovarian cancer. To
      clarify the roles of claudins in ovarian tumorigenesis, we have generated human
      ovarian surface epithelial (HOSE) cells constitutively expressing wild-type
      claudin-3 and claudin-4. Expression of these claudins in HOSE cells increased
      cell invasion and motility as measured by Boyden chamber assays and wound-healing
      experiments. Conversely, small interfering RNA (siRNA)-mediated knockdown of
      claudin-3 and claudin-4 expression in ovarian cancer cell lines reduced invasion.
      Claudin expression also increased cell survival in HOSE cells but did not
      significantly affect cell proliferation. Moreover, the claudin-expressing ovarian
      epithelial cells were found to have increased matrix metalloproteinase-2 (MMP-2)
      activity indicating that claudin-mediated increased invasion might be mediated
      through the activation of MMP proteins. However, siRNA inactivation of claudins
      in ovarian cancer cell lines did not have a significant effect on the high
      endogenous MMP-2 activity present in these cells, showing that malignant cells
      have alternative or additional pathways to fully activate MMP-2. Taken together,
      our results suggest that claudin overexpression may promote ovarian tumorigenesis
      and metastasis through increased invasion and survival of tumor cells.

PMID- 16103091
TI  - Depletion of mutant p53 and cytotoxicity of histone deacetylase inhibitors.
AB  - Mutant p53 is a cancer-specific target for pharmacologic intervention. We show
      that histone deacetylase inhibitors such as FR901228 and trichostatin A
      completely depleted mutant p53 in cancer cell lines. This depletion was preceded
      by induction of p53-regulated transcription. In cells with mutant p53 pretreated
      with histone deacetylase inhibitors, DNA damage further enhanced the p53 trans
      function. Furthermore, histone deacetylase inhibitors were preferentially
      cytotoxic to cells with mutant p53 rather than to cells lacking wild-type p53. We
      suggest that, by either restoring or mimicking p53 trans-functions, histone
      deacetylase inhibitors initiate degradation of mutant p53. Because mutant p53 is
      highly expressed, a sudden restoration of p53-like functions is highly cytotoxic
      to cells with mutant p53. In a broader perspective, this shows how selectivity
      may be achieved by targeting a non-cancer-specific target, such as histone
      deacetylases, in the presence of a cancer-specific alteration, such as mutant
      p53.

PMID- 16103092
TI  - Telomerase-dependent virotherapy overcomes resistance of hepatocellular
      carcinomas against chemotherapy and tumor necrosis factor-related apoptosis
      inducing ligand by elimination of Mcl-1.
AB  - Hepatocellular carcinomas (HCC) are drug-resistant tumors that frequently possess
      high telomerase activity. It was therefore the aim of our study to investigate
      the potential of telomerase-dependent virotherapy in multimodal treatment of HCC.
      In contrast to normal liver, HCC xenografts showed high telomerase activity,
      resulting in tumor-restricted expression of E1A by a telomerase-dependent
      replicating adenovirus (hTERT-Ad). Neither tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) or chemotherapy alone nor the combined
      treatment with both agents resulted in significant destruction of HCC cells.
      Application of hTERT-Ad at low titers was also not capable to destroy HCC cells,
      but telomerase-dependent virotherapy overcame the resistance of HCC against TRAIL
      and chemotherapy. The synergistic effects are explained by a strong down
      regulation of Mcl-1 expression through hTERT-Ad that sensitizes HCC for TRAIL-
      and chemotherapy-mediated apoptosis. To investigate whether down-regulation of
      Mcl-1 alone is sufficient to explain synergistic effects observed with
      virotherapy, Mcl-1 expression was inhibited by RNA interference. Treatment with
      Mcl-1-siRNA significantly enhanced caspase-3 activity after chemotherapy and
      TRAIL application, confirming that elimination of Mcl-1 is responsible for the
      drug sensitization by hTERT-Ad. Consistent with these results, heterologous
      overexpression of Mcl-1 significantly reduced the sensitization of hTERT-Ad
      transduced cells against apoptosis-inducing agents. Chemotherapy did not
      interfere with quantitative hTERT-Ad production in HCC cells. Whereas hTERT-Ad
      virotherapy alone was only capable to inhibit the growth of Hep3B xenografts,
      virochemotherapy resulted in vast destruction of the drug-resistant HCC. In
      conclusion our data indicate that telomerase-dependent virotherapy is an
      attractive strategy to overcome the natural resistance of HCC against anticancer
      drugs by elimination of Mcl-1.

PMID- 16103093
TI  - Signaling through IFN regulatory factor-5 sensitizes p53-deficient tumors to DNA
      damage-induced apoptosis and cell death.
AB  - Human IFN regulatory factor-5 (IRF-5) is a candidate tumor suppressor gene that
      mediates cell arrest, apoptosis, and immune activation. Here we show that ectopic
      IRF-5 sensitizes p53-proficient and p53-deficient colon cancer cells to DNA
      damage-induced apoptosis. The combination IFN-beta and irinotecan (CPT-11)
      cooperatively inhibits cell growth and IRF-5 synergizes with it to further
      promote apoptosis. The synergism is due to IRF-5 signaling since a striking
      defect in apoptosis and cell death was observed in IRF-5-deficient cells, which
      correlated well with a reduction in DNA damage-induced cellular events.
      Components of this IRF-5 signaling pathway are investigated including a mechanism
      for DNA damage-induced IRF-5 activation. Thus, IRF-5-regulated pathways may serve
      as a target for cancer therapeutics.

PMID- 16103094
TI  - Novel fusion protein approach for efficient high-throughput screening of small
      molecule-mediating protein-protein interactions in cells and living animals.
AB  - Networks of protein interactions execute many different intracellular pathways.
      Small molecules either synthesized within the cell or obtained from the external
      environment mediate many of these protein-protein interactions. The study of
      these small molecule-mediated protein-protein interactions is important in
      understanding abnormal signal transduction pathways in a variety of disorders, as
      well as in optimizing the process of drug development and validation. In this
      study, we evaluated the rapamycin-mediated interaction of the human proteins
      FK506-binding protein (FKBP12) rapamycin-binding domain (FRB) and FKBP12 by
      constructing a fusion of these proteins with a split-Renilla luciferase or a
      split enhanced green fluorescent protein (split-EGFP) such that complementation
      of the reporter fragments occurs in the presence of rapamycin. Different linker
      peptides in the fusion protein were evaluated for the efficient maintenance of
      complemented reporter activity. This system was studied in both cell culture and
      xenografts in living animals. We found that peptide linkers with two or four
      EAAAR repeat showed higher protein-protein interaction-mediated signal with lower
      background signal compared with having no linker or linkers with amino acid
      sequences GGGGSGGGGS, ACGSLSCGSF, and ACGSLSCGSFACGSLSCGSF. A 9 +/- 2-fold
      increase in signal intensity both in cell culture and in living mice was seen
      compared with a system that expresses both reporter fragments and the interacting
      proteins separately. In this fusion system, rapamycin induced heterodimerization
      of the FRB and FKBP12 moieties occurred rapidly even at very lower concentrations
      (0.00001 nmol/L) of rapamycin. For a similar fusion system employing split-EGFP,
      flow cytometry analysis showed significant level of rapamycin-induced
      complementation.

PMID- 16103095
TI  - WTH3, which encodes a small G protein, is differentially regulated in multidrug
      resistant and sensitive MCF7 cells.
AB  - The WTH3 gene's biological characteristics and relationship to multidrug
      resistance (MDR) were investigated further. Results showed that WTH3 was mainly
      located in the cytosol and capable of binding to GTP. In addition, WTH3's
      promoter function was significantly attenuated in MDR (MFC7/AdrR) relative to non
      MDR (MCF7/WT) cells. Advanced analyses indicated that two mechanisms could be
      involved in WTH3's down-regulation: DNA methylation and trans-element
      modulations. It was found that the 5' end portion of a CpG island in WTH3's
      promoter was hypermethylated in MCF7/AdrR but not MCF7/WT cells, which could have
      a negative effect on the WTH3 promoter. This idea was supported by the
      observation that a 45-bp sequence (DMR45) in this differentially methylated
      region positively influenced promoter activity. We also discovered that different
      nuclear proteins in MCF7/AdrR and MCF7/WT cells bound to methylated or
      nonmethylated DMR45. Moreover, a sequence containing a unique repeat that was
      also a positive cis-element for the promoter was attached by different
      transcription factors depending on whether they were prepared from MCF7/AdrR or
      MCF7/WT cells. These molecular changes, apparently induced by drug treatment,
      resulted in WTH3's down regulation in MDR cells. Therefore, present studies
      support previous observations that WTH3, as a negative regulator, participates in
      MDR development in MCF7/AdrR cells.

PMID- 16103096
TI  - Perifosine inhibits multiple signaling pathways in glial progenitors and
      cooperates with temozolomide to arrest cell proliferation in gliomas in vivo.
AB  - Perifosine is an oral Akt inhibitor which exerts a marked cytotoxic effect on
      human tumor cell lines, and is currently being tested in several phase II trials
      for treatment of major human cancers. However, the efficacy of perifosine in
      human gliomas has not been established. As Akt is activated in approximately 70%
      of human glioblastomas, we investigated the impact of perifosine on glia in
      culture and on a mouse glioma model in vivo. Here we show that perifosine
      strongly reduces phosphorylation levels of Akt and extracellular signal-regulated
      kinase (Erk) 1/2, induces cell cycle arrest in G1 and G2, and causes dose
      dependent growth inhibition of mouse glial progenitors in which Akt and/or Ras
      Erk 1/2 pathways are activated. Furthermore, because temozolomide is a common
      oral alkylating agent used in the treatment of gliomas, we investigated the
      effect of perifosine in combination with temozolomide. We observed an enhanced
      effect when both were used in culture. With these results, we combined perifosine
      and temozolomide as treatment of platelet-derived growth factor B-driven gliomas
      in mice. Animal studies showed that perifosine and temozolomide combination
      therapy was more effective than temozolomide treatment alone (P < 0.01). These
      results indicate that perifosine is an effective drug in gliomas in which Akt and
      Ras-Erk 1/2 pathways are frequently activated, and may be a new candidate for
      glioma treatment in the clinic.

PMID- 16103097
TI  - Reactive oxygen species regulate caspase activation in tumor necrosis factor
      related apoptosis-inducing ligand-resistant human colon carcinoma cell lines.
AB  - The effects of reactive oxygen species (ROS) on tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL)-induced apoptosis in solid cancers have yet to
      be clearly defined. In this study, we found that the classic uncoupler of
      oxidative phosphorylation, carbonyl cyanide m-chlorophenylhydrazone (CCCP),
      induced a reduction in DeltaPsim and generation of ROS. This uncoupling effect
      enhanced TRAIL-induced apoptosis in TRAIL-resistant human colon carcinoma cell
      lines (RKO, HT29, and HCT8). Sensitization was inhibited by benzyloxycarbonyl
      valine-alanine-aspartate fluoromethylketone, indicating the requirement for
      caspase activation. CCCP per se did not induce apoptosis or release of
      proapoptotic factors from mitochondria. Generation of ROS by CCCP was responsible
      for TRAIL-induced Bax and caspase activation because scavenging ROS completely
      abrogated apical caspase-8 activation and further downstream events leading to
      cell death. Overexpression of Bcl-2 did not prevent the initial loss of DeltaPsim
      and ROS generation following CCCP treatment, but did prevent cell death following
      TRAIL and CCCP exposure. Uncoupling of mitochondria also facilitated TRAIL
      induced release of proapoptotic factors. X-linked inhibitor of apoptosis
      overexpression abrogated TRAIL-induced apoptosis in the presence of CCCP and
      decreased initiator procaspase-8 processing, indicating that additional
      processing of caspase-8 required initiation of a mitochondrial amplification loop
      via effector caspases. Of interest, depletion of caspase-9 in RKO cells did not
      protect cells from TRAIL/CCCP-induced apoptosis, indicating that apoptosis
      occurred via a caspase-9-independent pathway. Data suggest that in the presence
      of mitochondrial-derived ROS, TRAIL induced mitochondrial release of Smac/DIABLO
      and inactivation of X-linked inhibitor of apoptosis through caspase-9-independent
      activation of caspase 3.

PMID- 16103098
TI  - Cystine-glutamate transporter SLC7A11 in cancer chemosensitivity and
      chemoresistance.
AB  - SLC7A11 (xCT), together with SLC3A2 (4F2hc), encodes the heterodimeric amino acid
      transport system x(c)-, which mediates cystine-glutamate exchange and thereby
      regulates intracellular glutathione levels. We used microarrays to analyze gene
      expression of transporters in 60 human cancer cell lines used by the National
      Cancer Institute for drug screening (NCI-60). The expression of SLC7A11 showed
      significant correlation with that of SLC3A2 (r = 0.66), which in turn correlated
      with SLC7A5 (r = 0.68), another known partner for SLC3A2, and with T1A-2 (r =
      0.60; all P < 0.0001). Linking expression of SLC7A11 with potency of 1,400
      candidate anticancer drugs identified 39 showing positive correlations, e.g.,
      amino acid analogue, L-alanosine, and 296 with negative correlations, e.g.,
      geldanamycin. However, no significant correlation was observed with the
      geldanamycin analogue 17-allylamino, 17-demethoxygeldanamycin (17-AAG).
      Inhibition of transport system x(c)- with glutamate or (S)-4-carboxyphenylglycine
      in lung A549 and HOP-62, and ovarian SK-OV-3 cells, reduced the potency of L
      alanosine and lowered intracellular glutathione levels. This further resulted in
      increased potency of geldanamycin, with no effect on 17-AAG. Down-regulation of
      SLC7A11 by small interfering RNA affected drug potencies similarly to transport
      inhibitors. The inhibitor of gamma-glutamylcysteine synthetase, buthionine
      sulfoximine, also decreased intracellular glutathione levels and enhanced potency
      of geldanamycin, but did not affect L-alanosine. These results indicate that
      SLC7A11 mediates cellular uptake of L-alanosine but confers resistance to
      geldanamycin by supplying cystine for glutathione maintenance. SLC7A11 expression
      could serve as a predictor of cellular response to L-alanosine and glutathione
      mediated resistance to geldanamycin, yielding a potential target for increasing
      chemosensitivity to multiple drugs.

PMID- 16103099
TI  - RECK-mediated suppression of tumor cell invasion is regulated by glycosylation in
      human tumor cell lines.
AB  - RECK, a glycosylphosphatidylinositol (GPI)-anchored glycoprotein, negatively
      regulates matrix metalloproteinases (MMP), such as MMP-9, and inhibits tumor
      invasion and metastasis. The predicted amino acid sequence of human RECK includes
      five putative N-glycosylation sites; however, the precise biochemical role of
      glycosylated RECK remains unknown. In this study, we examined the link between
      glycosylation and the function of RECK in human tumor cell lines. RECK protein
      was glycosylated at Asn86, Asn200, Asn297, and Asn352 residues but not at the
      Asn39 residue in HT1080 cells. Although the glycosylation of these asparagine
      sites did not play a role in the cell surface localization of RECK as a GPI
      anchored protein, the glycosylation of RECK Asn297 residue was involved in the
      suppression of MMP-9 secretion and Asn352 residue was necessary to inhibit MMP-2
      activation. Moreover, RECK-suppressed tumor cell invasion was reversed by
      inhibiting glycosylation at Asn86, Asn297, and Asn352 residues of RECK. Thus,
      these findings indicate that glycosylation mediates RECK suppression of tumor
      cell invasion by multiple mechanisms such as suppressing MMP-9 secretion and
      inhibiting MMP-2 activation.

PMID- 16103100
TI  - The protein kinase Cbeta-selective inhibitor, Enzastaurin (LY317615.HCl),
      suppresses signaling through the AKT pathway, induces apoptosis, and suppresses
      growth of human colon cancer and glioblastoma xenografts.
AB  - Activation of protein kinase Cbeta (PKCbeta) has been repeatedly implicated in
      tumor-induced angiogenesis. The PKCbeta-selective inhibitor, Enzastaurin
      (LY317615.HCl), suppresses angiogenesis and was advanced for clinical development
      based upon this antiangiogenic activity. Activation of PKCbeta has now also been
      implicated in tumor cell proliferation, apoptosis, and tumor invasiveness.
      Herein, we show that Enzastaurin has a direct effect on human tumor cells,
      inducing apoptosis and suppressing the proliferation of cultured tumor cells.
      Enzastaurin treatment also suppresses the phosphorylation of GSK3betaser9,
      ribosomal protein S6(S240/244), and AKT(Thr308). Oral dosing with Enzastaurin to
      yield plasma concentrations similar to those achieved in clinical trials
      significantly suppresses the growth of human glioblastoma and colon carcinoma
      xenografts. As in cultured tumor cells, Enzastaurin treatment suppresses the
      phosphorylation of GSK3beta in these xenograft tumor tissues. Enzastaurin
      treatment also suppresses GSK3beta phosphorylation to a similar extent in
      peripheral blood mononuclear cells (PBMCs) from these treated mice. These data
      show that Enzastaurin has a direct antitumor effect and that Enzastaurin
      treatment suppresses GSK3beta phosphorylation in both tumor tissue and in PBMCs,
      suggesting that GSK3beta phosphorylation may serve as a reliable pharmacodynamic
      marker for Enzastaurin activity. With previously published reports, these data
      support the notion that Enzastaurin suppresses tumor growth through multiple
      mechanisms: direct suppression of tumor cell proliferation and the induction of
      tumor cell death coupled to the indirect effect of suppressing tumor-induced
      angiogenesis.

PMID- 16103101
TI  - Substituted purine analogues define a novel structural class of catalytic
      topoisomerase II inhibitors.
AB  - By screening 1,990 compounds from the National Cancer Institute diversity set
      library against human topoisomerase IIalpha, we identified a novel catalytic
      topoisomerase II inhibitor NSC35866, a S6-substituted analogue of thioguanine. In
      addition to inhibiting the DNA strand passage reaction of human topoisomerase
      IIalpha, NSC35866 also inhibited its ATPase reaction. NSC35866 primarily
      inhibited DNA-stimulated ATPase activity, whereas DNA-independent ATPase activity
      was less sensitive to inhibition. We compared the mode of topoisomerase II ATPase
      inhibition induced by NSC35866 with that of 12 other substituted purine analogues
      of different chemical classes. The ability of thiopurines with free SH
      functionalities to inhibit topoisomerase II ATPase activity was completely
      abolished by DTT, suggesting that these thiopurines inhibit topoisomerase II
      ATPase activity by covalently modifying free cysteine residues. In contrast,
      NSC35866 as well as two O6-substituted guanine analogues, O6-benzylguanine and
      NU2058, could inhibit topoisomerase II ATPase activity in the presence of DTT,
      indicating that they have a different mechanism of inhibition. NSC35866 did not
      increase the level of topoisomerase II covalent cleavable complexes with DNA,
      indicating that it is a catalytic inhibitor and not a poison. NSC35866 was also
      capable of inducing a salt-stable complex of topoisomerase II on closed circular
      DNA. In accordance with these biochemical data, NSC35866 could antagonize
      etoposide-induced cytotoxicity and DNA breaks in human and murine cancer cells,
      confirming that NSC35866 also functions as a catalytic topoisomerase II inhibitor
      in cells.

PMID- 16103102
TI  - FTY720 induces apoptosis in multiple myeloma cells and overcomes drug resistance.
AB  - The novel immunomodulator FTY720 down-modulates sphingosine-1-phosphate receptor
      1 on lymphocytes at low nanomolar concentrations, thereby inhibiting sphingosine
      1-phosphate receptor 1-dependent egress of lymphocytes from lymph nodes into
      efferent lymphatics and blood. At high micromolar concentration, FTY720 has been
      shown to induce growth inhibition and/or apoptosis in human cancer cells in
      vitro. In this study, we investigated the biological effects of FTY720 on
      multiple myeloma cells. We found that FTY720 induces potent cytotoxicity against
      drug-sensitive and drug-resistant multiple myeloma cell lines as well as freshly
      isolated tumor cells from multiple myeloma patients who do not respond to
      conventional agents. FTY720 triggers activation of caspase-8, -9, and -3,
      followed by poly(ADP-ribose) polymerase cleavage. Interestingly, FTY720 induces
      alterations in mitochondrial membrane potential (DeltaPsim) and Bax cleavage,
      followed by translocation of cytochrome c and Smac/Diablo from mitochondria to
      the cytosol. In combination treatment studies, both dexamethasone and anti-Fas
      antibodies augment anti-multiple myeloma activity induced by FTY720. Neither
      interleukin-6 nor insulin-like growth factor-I, which both induce multiple
      myeloma cell growth and abrogate dexamethasone-induced apoptosis, protect against
      FTY720-induced growth inhibition. Importantly, growth of multiple myeloma cells
      adherent to bone marrow stromal cells is also significantly inhibited by FTY720.
      Finally, it down-regulates interleukin-6-induced phosphorylation of Akt, signal
      transducers and activators of transcription 3, and p42/44 mitogen-activated
      protein kinase; insulin-like growth factor-I-triggered Akt phosphorylation; and
      tumor necrosis factor alpha-induced IkappaBalpha and nuclear factor-kappaB p65
      phosphorylation. These results suggest that FTY720 overcomes drug resistance in
      multiple myeloma cells and provide the rationale for its clinical evaluation to
      improve patient outcome in multiple myeloma.

PMID- 16103103
TI  - Identification of mechanisms underlying transporter associated with antigen
      processing deficiency in metastatic murine carcinomas.
AB  - Expression of transporter associated with antigen processing (TAP) is often lost
      in metastatic carcinomas, resulting in defective antigen processing and
      presentation and escape of the cancer cells from immune surveillance. In this
      study, the nature of TAP deficiencies in tumors was investigated. By chromatin
      immunoprecipitation assay, we showed that the recruitment of RNA polymerase II to
      the TAP-1 gene was impaired in TAP-deficient cells derived from murine melanoma,
      prostate, and lung carcinomas, compared with TAP-expressing fibroblasts and
      lymphoma cells. This suggested that the deficiency in TAP-1 expression resulted,
      at least partially, from a relatively low level of transcription of the TAP-1
      gene. Furthermore, levels of TAP-1 promoter activity, as assessed by stable
      transfections with a reporter construct containing the TAP-1 promoter, were
      relatively low in TAP-deficient cells. To examine genetic heritability of
      regulators of TAP-1 promoter activity, TAP- and MHC class I-deficient cells of H
      2b origin were fused with wild-type fibroblasts of H-2k origin. Fusion with TAP
      expressing cells complemented the low levels of TAP-1 promoter activity in TAP
      deficient cells. However, these fused cells exhibited lower levels of TAP-1 mRNA
      and H-2k than unfused fibroblasts. Further analysis showed that TAP-1 mRNA
      stability was lower in fused carcinoma fibroblasts than in unfused fibroblasts.
      Based on these results, we propose that TAP deficiency in many carcinomas is
      caused by a decrease in activity/expression of trans-acting factors regulating
      TAP-1 promoter activity, as well as a decrease in TAP-1 mRNA stability. These
      results have significant implications for understanding immune evasion mechanisms
      in tumors.

PMID- 16103104
TI  - Cyclophosphamide inhibition of anti-CD40 monoclonal antibody-based therapy of B
      cell lymphoma is dependent on CD11b+ cells.
AB  - Monoclonal antibody (mAb)-based immunotherapy is now established as an important
      option for treating some cancers. The antitumor effects may be further enhanced
      by combining mAb with conventional chemotherapy. Certain novel immunomodulatory
      mAbs such as anti-CD40 have shown significant activity in preclinical models. We
      therefore assessed the efficacy of combining anti-CD40 mAb, known to elicit CTL
      responses against murine lymphoma models with the commonly used cytotoxic drug,
      cyclophosphamide. Using the syngeneic tumor model, BCL1, we have shown that
      timing of cyclophosphamide relative to mAb is critical to therapeutic outcome.
      Pretreatment with cyclophosphamide 7 to 10 days prior to mAb results in markedly
      reduced survival levels, similar to that achieved with cyclophosphamide alone.
      Conversely, when anti-CD40 is given before cyclophosphamide, the level of tumor
      protection was moderately increased. In vivo tracking experiments reveal that
      pretreatment with cyclophosphamide leads to diminished CTL expansion, as well as
      an increased number of CD11b+ cells that display an activated phenotype. These
      latter cells are able to inhibit T-cell proliferation, at least in part via
      production of nitric oxide, but do not induce T-cell apoptosis. Furthermore,
      adoptive transfer of the induced CD11b+ cells is sufficient to inhibit anti-CD40
      therapy in tumor-bearing recipients. We have shown that the timing of
      cyclophosphamide relative to mAb administration is critical to the therapeutic
      outcome, and although the combination can improve survival, cyclophosphamide
      given prior to immunotherapy may generate a population of myeloid cells that can
      interfere with CTL responses and compromise the therapeutic outcome.

PMID- 16103105
TI  - MICA expressed by multiple myeloma and monoclonal gammopathy of undetermined
      significance plasma cells Costimulates pamidronate-activated gammadelta
      lymphocytes.
AB  - Amino-biphosphonates (like pamidronate) activate human Vgamma9/Vdelta2 T
      lymphocytes and promote their cytotoxicity against multiple myeloma cells. T-cell
      receptor (TCR)-mediated effector functions of gammadelta cells are enhanced upon
      triggering of the activating receptor NKG2D by MICA, a stress-inducible antigen
      expressed by epithelial and some hematopoietic tumors, including multiple
      myeloma. Here we show that MICA was expressed not only by myeloma cell lines and
      by 6 of 10 primary multiple myeloma cells from patients but also by bone marrow
      plasma cells from all (six of six) patients with preneoplastic gammopathy
      (monoclonal gammopathy of undetermined significance, MGUS), a direct precursor of
      multiple myeloma. Moreover, compared with multiple myeloma plasma cells, MICA was
      expressed by MGUS plasma cells at significantly (P < 0.05) higher levels. MICA
      expressed by myeloma cell lines contributed to killing and IFN-gamma production
      by Vgamma9/Vdelta2 cells only upon pamidronate treatment, suggesting a dual
      interaction between Vgamma9/Vdelta2 lymphocytes and multiple myeloma plasma cells
      involving both TCR triggering and NKG2D-mediated signals. Finally, MICA enhanced
      killing of freshly derived, pamidronate-treated multiple myeloma cells from
      patients by gammadelta cells, as indicated by the significantly (P < 0.05) higher
      gammadelta cytotoxicity against MICA-positive rather than MICA-negative multiple
      myeloma cells. Our results indicate that MICA expressed by monoclonal plasma
      cells is functional and correlates with disease stages, suggesting a role for the
      molecule in the immune surveillance against multiple myeloma. Moreover,
      pamidronate-activated Vgamma9/Vdelta2 lymphocytes can be exploited in the immune
      therapy of early stages multiple myeloma and possibly of premalignant disease.

PMID- 16103106
TI  - S179D prolactin increases vitamin D receptor and p21 through up-regulation of
      short 1b prolactin receptor in human prostate cancer cells.
AB  - In this study, we further investigated the mechanisms by which
      pseudophosphorylated prolactin (S179D PRL) inhibits the growth of human prostate
      cancer cells. When treated with S179D PRL for 3 days, LnCAP cells responded by
      increasing expression of the vitamin D receptor (VDR) and the cell cycle
      regulatory molecule, p21, whereas PC3 and DU145 cells did not. After 5 days of
      treatment, both PC3 and DU145 cells responded. Untreated LnCAP cells express the
      short 1b form (SF1b) of the human prolactin receptor, but DU145 and PC3 cells
      express only low amounts of this receptor until elevated by treatment with S179D
      PRL. DU145 and PC3 cells become sensitive to the negative effects of S179D PRL on
      cell number after induction of the SF1b. Transfection of either SF1b or SF1a into
      PC3 or DU145 cells made them sensitive to S179D PRL in the 3-day time frame, a
      finding that was not duplicated by transfection with the long form of the
      receptor. Treatment of LnCAP cells with S179D PRL increased long-term activation
      of extracellular signal-regulated kinase 1/2 (ERK1/2). This did not occur in PC3
      and DU145 cells until transfection with SF1a/SF1b. Blockade of ERK signaling
      eliminated S179D PRL-stimulated expression of the VDR and p21 in LnCAP cells and
      transfected PC3 and DU145 cells. We conclude that initiation of alternative
      splicing to produce SF1b, and subsequent altered signaling, contribute to the
      growth inhibitory mechanisms of S179D PRL. This is the first indication of a role
      for short prolactin receptors in the regulation of cell proliferation.

PMID- 16103107
TI  - A haplotype-based case-control study of BRCA1 and sporadic breast cancer risk.
AB  - Rare, highly penetrant germ line mutations in BRCA1 strongly predispose women to
      a familial form of breast and ovarian cancer. Whether common variants (either
      coding or noncoding) at this locus contribute to the more common form of the
      disease is not yet known. We tested common variation across the BRCA1 locus in
      African American, Native Hawaiian, Japanese, Latino, and White women in the
      Multiethnic Cohort Study. Specifically, 28 single nucleotide polymorphisms (SNPs)
      spanning the BRCA1 gene were used to define patterns of common variation in these
      populations. The majority of SNPs were in strong linkage disequilibrium with one
      another, indicating that our survey captured most of the common inherited
      variation across this gene. Nine tagging SNPs, including five missense SNPs, were
      selected to predict the common BRCA1 variants and haplotypes among the non
      African American groups (five additional SNPs were required for African
      Americans) and genotyped in a breast cancer case-control study nested in the
      Multiethnic Cohort Study (cases, n = 1,715; controls, n = 2,502). We found no
      evidence for significant associations between common variation in BRCA1 and risk
      of breast cancer. Given the large size of our study population and detailed
      analysis of the locus, this result indicates either that common variants in BRCA1
      do not substantially influence sporadic breast cancer risk, or that unmeasured
      heterogeneity in the breast cancer phenotype or unmeasured interactions with
      genetic or environmental exposures obscure our ability to detect any influence
      that may be present.

PMID- 16103108
TI  - Neural stem cell differentiation is dependent upon endogenous caspase 3 activity.
AB  - Caspase proteases have become the focal point for the development and application
      of anti-apoptotic therapies in a variety of central nervous system diseases.
      However, this approach is based on the premise that caspase function is limited
      to invoking cell death signals. Here, we show that caspase-3 activity is elevated
      in nonapoptotic differentiating neuronal cell populations. Moreover, peptide
      inhibition of protease activity effectively inhibits the differentiation process
      in a cultured neurosphere model. These results implicate caspase-3 activation as
      a conserved feature of neuronal differentiation and suggest that targeted
      inhibition of this protease in neural cell populations may have unintended
      consequences.

PMID- 16103109
TI  - New possible roles for aquaporin-4 in astrocytes: cell cytoskeleton and
      functional relationship with connexin43.
AB  - Aquaporin-4 (AQP4), the main water channel in the brain, is expressed in the
      perivascular membranes of mouse, rat, and human astrocytes. In a previous study,
      we used small interfering RNA (siRNA) to specifically knock down AQP4 in rat
      astrocyte primary cultures and found that together with reduced osmotic
      permeability, AQP4 knockdown (KD) led to altered cell morphology. However, a
      recent report on primary cultured astrocytes from AQP4 null mice (KO) showed no
      morphological differences compared with wild types. In this study, we compared
      the effect of AQP4 KD in mouse, rat, and human astrocyte primary cultures and
      found that AQP4 KD in human astrocytes resulted in a morphological phenotype
      similar to that found in rat. In contrast, AQP4 KD in mouse astrocytes caused
      only very mild morphological changes. The actin cytoskeleton of untreated
      astrocytes exhibited strong species-specific differences, with F-actin being
      organized in cortical bands in mouse and in stress fibers in rat and human
      astrocytes. Surprisingly, as a consequence of AQP4 KD, F-actin cytoskeleton was
      depolymerized in rat and human whereas it was completely rearranged in mouse
      astrocytes. Although AQP4 KD induced alterations of the cell cytoskeleton, we
      found that the expression of dystrophin (DP71), beta-dystroglycan, and alpha
      syntrophin was not altered. AQP4 KD in cultured mouse astrocytes produced strong
      down-regulation of connexin43 (Cx43) with a concomitant reduction in cell
      coupling while no major alterations in Cx43 expression were found in rat and
      human cells. Taken together, these results demonstrate that with regard to these
      properties, human astrocytes in culture are more similar to rat than to mouse
      astrocytes. Moreover, even though AQP4 KD in mouse astrocytes did not result in a
      dramatic morphological phenotype, it induced a remarkable rearrangement of F
      actin, not related to disruption of the dystrophin complex, indicating a primary
      role of this water channel in the cytoskeleton changes observed. Finally, the
      strong down-regulation of Cx43 and cell coupling in AQP4 KD mouse astrocytes
      indicate that a functional relationship likely exists between water channels and
      gap junctions in brain astrocytes.

PMID- 16103110
TI  - Involvement of N-terminal-extended form of sphingosine kinase 2 in serum
      dependent regulation of cell proliferation and apoptosis.
AB  - Sphingosine kinase (SPHK) 1 is implicated in the regulation of cell proliferation
      and anti-apoptotic processes by catalyzing the formation of an important
      bioactive messenger, sphingosine 1-phosphate. Unlike the proliferative action of
      SPHK1, another isozyme, SPHK2, has been shown to possess anti-proliferative or
      pro-apoptotic action. Molecular mechanisms of SPHK2 action, however, are largely
      unknown. The present studies were undertaken to characterize the N-terminal
      extended form of SPHK2 (SPHK2-L) by comparing it with the originally reported
      form, SPHK2-S. Real-time quantitative PCR analysis revealed that SPHK2-L mRNA is
      the major form in several human cell lines and tissues. From sequence analyses it
      was concluded that SPHK2-L is a species-specific isoform that is expressed in
      human but not in mouse. At the protein level it has been demonstrated by
      immunoprecipitation studies that SPHK2-L is the major isoform in human hepatoma
      HepG2 cells. SPHK2-L, when expressed in human embryonic kidney (HEK) 293 cells,
      did not show any inhibition of DNA synthesis in the presence of serum, whereas it
      showed marked inhibition in the absence of serum. Moreover, serum deprivation
      resulted in the translocation of SPHK2-L into the nuclei. In addition, serum
      deprivation induced SPHK2-L expression in HEK293 cells. Furthermore, suppression
      of SPHK2 by small interfering RNA treatment prevented serum deprivation- or drug
      induced apoptosis in HEK293 cells. Taken together, these results indicate that a
      major form of SPHK2 splice variant, SPHK2-L, in human cells does not inhibit DNA
      synthesis under normal conditions and that SPHK2-L accumulation in the nucleus
      induced by serum deprivation may be involved in the cessation of cell
      proliferation or apoptosis depending on the cell type.

PMID- 16103111
TI  - Involvement of the p97-Ufd1-Npl4 complex in the regulated endoplasmic reticulum
      associated degradation of inositol 1,4,5-trisphosphate receptors.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) receptors form tetrameric, IP(3)-gated
      channels in endoplasmic reticulum membranes that govern the release of Ca(2+)
      from this organelle. In response to activation of certain G protein-coupled
      receptors that persistently elevate IP(3) concentration, IP(3) receptors are
      ubiquitinated and degraded by the ubiquitin-proteasome pathway. IP(3) receptor
      ubiquitination is mediated by the ubiquitin-conjugating enzyme, (mam)Ubc7, a
      component of the endoplasmic reticulum-associated degradation pathway. However,
      the mechanism by which ubiquitinated IP(3) receptors are transferred to the
      proteasome is not known. Here, we examine this process and show in several
      mammalian cell types that the ATPase p97 associates with IP(3) receptors in
      response to hormonal stimuli that induce IP(3) receptor ubiquitination. To
      examine the functional relevance of the p97 interaction with IP(3) receptors, we
      stably and specifically reduced p97 protein levels by 62 +/- 3% in Rat-1
      fibroblasts using RNA interference. In these cells, endothelin-1-induced IP(3)
      receptor degradation was markedly retarded and the accumulation of ubiquitinated
      IP(3) receptors was markedly enhanced. These effects were reversed by expression
      of exogenous p97. In addition, Ufd1 and Npl4, which complex with p97, also
      associated with IP(3) receptors upon hormonal stimulation. We conclude that the
      p97-Ufd1-Npl4 complex couples ubiquitinated IP(3) receptors to proteasomal
      degradation and, thus, plays a key role in IP(3) receptor processing. These data
      also establish that the p97-Ufd1-Npl4 complex mediates endoplasmic reticulum
      associated degradation in mammalian cells.

PMID- 16103112
TI  - Two functional active conformations of the integrin {alpha}2{beta}1, depending on
      activation condition and cell type.
AB  - For several integrins, the existence of multiple conformational states has been
      studied intensively. For the integrin alpha2beta1, a major collagen receptor on
      platelets and other cell types, however, no such experimental data were available
      thus far. Recently, our group has developed a monoclonal antibody IAC-1 sensitive
      to the molecular conformation of alpha2beta1 because it only binds to the
      activated state of alpha2beta1 on platelets, induced upon inside-out signaling.
      By investigating IAC-1 binding in combination with collagen binding after inside
      out stimulation and outside manipulation, we demonstrated the existence of three
      different conformations of alpha2beta1 on platelets and Chinese hamster ovary
      cells as follows: (i) a nonactivated, resting state with no collagen nor IAC-1
      binding; (ii) an intermediate state, induced by outside manipulation, with
      collagen but no IAC-1 binding; and (iii) a fully activated state, induced after
      inside-out stimulation, with both collagen and IAC-1 binding. Moreover, these
      different conformational states of alpha2beta1 are dependent on the cell type
      where alpha2beta1 is expressed, as IAC-1 binding to peripheral blood mononuclear
      cells and Jurkat cells could also be induced by outside manipulation, in contrast
      to platelets and alpha2beta1-expressing Chinese hamster ovary cells. Finally, we
      revealed a functional relevance for these different conformational states because
      the conformation of alpha2beta1, induced after outside manipulation, resulted in
      significantly more cell spreading on coated collagen compared with nonactivated
      or inside-out stimulated cells.

PMID- 16103113
TI  - Proteasomes mediate prolactin-induced receptor down-regulation and fragment
      generation in breast cancer cells.
AB  - Prolactin regulates a variety of physiological processes, including mammary gland
      growth and differentiation, and recent findings support an important role in
      breast cancer development and progression. However, little is known about the
      trafficking of its receptor, a member of the cytokine receptor superfamily. In
      the present study, we examined the effect of ligand on the endogenous "long"
      isoform of the prolactin receptor in breast cancer cells. We found that prolactin
      caused rapid and prolonged down-regulation of this receptor. The prolactin
      induced increase in degradation was blocked by inhibitors of both proteasomes and
      lysosomes. However, the ubiquitin-conjugating system was not required for
      internalization. Prolactin also resulted in the concomitant appearance of a cell
      associated prolactin receptor fragment containing the extracellular domain. This
      latter process required proteasomal, but not metalloprotease, activity,
      distinguishing it from ectodomain "shedding" of other membrane receptors, which
      are secreted as binding proteins. The prolactin receptor fragment was labeled by
      surface biotinylation and independent of protein synthesis. Together, these data
      indicated that prolactin binding initiates limited proteasomal cleavage of its
      receptor, generating a cell-associated fragment containing the extracellular
      domain. Our findings described a new potential mediator of prolactin action and a
      novel mechanism whereby proteasomes modulate cellular processes.

PMID- 16103114
TI  - Biochemical and functional characterization of membrane blebs purified from
      Neisseria meningitidis serogroup B.
AB  - Studies with purified aggregates of endotoxin have revealed the importance of
      lipopolysaccharide-binding protein (LBP)-dependent extraction and transfer of
      individual endotoxin molecules to CD14 in Toll-like receptor 4 (TLR4)-dependent
      cell activation. Endotoxin is normally embedded in the outer membrane of intact
      Gram-negative bacteria and shed membrane vesicles ("blebs"). However, the ability
      of LBP and CD14 to efficiently promote TLR4-dependent cell activation by membrane
      associated endotoxin has not been studied extensively. In this study, we used an
      acetate auxotroph of Neisseria meningitidis serogroup B to facilitate metabolic
      labeling of bacterial endotoxin and compared interactions of purified endotoxin
      aggregates and of membrane-associated endotoxin with LBP, CD14, and endotoxin
      responsive cells. The endotoxin, phospholipid, and protein composition of the
      recovered blebs indicate that the blebs derive from the bacterial outer membrane.
      Proteomic analysis revealed an unusual enrichment in highly cationic (pI > 9)
      proteins. Both purified endotoxin aggregates and blebs activate monocytes and
      endothelial cells in a LBP-, CD14-, and TLR4/MD-2-dependent fashion, but the
      blebs were 3-10-fold less potent when normalized for the amount of endotoxin
      added. Differences in potency correlated with differences in efficiency of LBP
      dependent delivery to and extraction of endotoxin by CD14. Both membrane
      phospholipids and endotoxin are extracted by LBP/soluble CD14 (sCD14) treatment,
      but only endotoxin.sCD14 reacts with MD-2 and activates cells. These findings
      indicate that the proinflammatory potency of endotoxin may be regulated not only
      by the intrinsic structural properties of endotoxin but also by its association
      with neighboring molecules in the outer membrane.

PMID- 16103115
TI  - A binding site tyrosine shapes desensitization kinetics and agonist potency at
      GluR2. A mutagenic, kinetic, and crystallographic study.
AB  - Binding of an agonist to the 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)
      propionic acid (AMPA) receptor family of the glutamate receptors (GluRs) results
      in rapid activation of an ion channel. Continuous application results in a non
      desensitizing response for agonists like kainate, whereas most other agonists,
      such as the endogenous agonist (S)-glutamate, induce desensitization. We
      demonstrate that a highly conserved tyrosine, forming a wedge between the agonist
      and the N-terminal part of the bi-lobed ligand-binding site, plays a key role in
      the receptor kinetics as well as agonist potency and selectivity. The AMPA
      receptor GluR2, with mutations in Tyr-450, were expressed in Xenopus laevis
      oocytes and characterized in a two-electrode voltage clamp setup. The mutation
      GluR2(Y450A) renders the receptor highly kainate selective, and rapid application
      of kainate to outside-out patches induced strongly desensitizing currents. When
      Tyr-450 was substituted with the larger tryptophan, the (S)-glutamate
      desensitization is attenuated with a 10-fold increase in steady-state/peak
      currents (19% compared with 1.9% at the wild type). Furthermore, the tryptophan
      mutant was introduced into the GluR2-S1S2J ligand binding core construct and co
      crystallized with kainate, and the 2.1-A x-ray structure revealed a slightly more
      closed ligand binding core as compared with the wild-type complex. Through
      genetic manipulations combined with structural and electrophysiological analysis,
      we report that mutations in position 450 invert the potency of two central
      agonists while concurrently strongly shaping the agonist efficacy and the
      desensitization kinetics of the AMPA receptor GluR2.

PMID- 16103116
TI  - Evidence for the regulatory role of the N-terminal helix of secretory
      phospholipase A(2) from studies on native and chimeric proteins.
AB  - The phospholipase A(2) (PLA(2)) enzymes are activated by binding to phospholipid
      membranes. Although the N-terminal alpha-helix of group I/II PLA(2)s plays an
      important role in the productive mode membrane binding of the enzymes, its role
      in the structural aspects of membrane-induced activation of PLA(2)s is not well
      understood. In order to elucidate membrane-induced conformational changes in the
      N-terminal helix and in the rest of the PLA(2), we have created semisynthetic
      human group IB PLA(2) in which the N-terminal decapeptide is joined with the
      (13)C-labeled fragment, as well as a chimeric protein containing the N-terminal
      decapeptide from human group IIA PLA(2) joined with a (13)C-labeled fragment of
      group IB PLA(2). Infrared spectral resolution of the unlabeled and (13)C-labeled
      segments suggests that the N-terminal helix of membrane-bound IB PLA(2) has a
      more rigid structure than the other helices. On the other hand, the overall
      structure of the chimeric PLA(2) is more rigid than that of the IB PLA(2), but
      the N-terminal helix is more flexible. A combination of homology modeling and
      polarized infrared spectroscopy provides the structure of membrane-bound chimeric
      PLA(2), which demonstrates remarkable similarity but also distinct differences
      compared with that of IB PLA(2). Correlation is delineated between structural and
      membrane binding properties of PLA(2)s and their N-terminal helices. Altogether,
      the data provide evidence that the N-terminal helix of group I/II PLA(2)s acts as
      a regulatory domain that mediates interfacial activation of these enzymes.

PMID- 16103117
TI  - Interaction of hemojuvelin with neogenin results in iron accumulation in human
      embryonic kidney 293 cells.
AB  - Type 2 hereditary hemochromatosis (HH) or juvenile hemochromatosis is an early
      onset, genetically heterogeneous, autosomal recessive disorder of iron overload.
      Type 2A HH is caused by mutations in the recently cloned hemojuvelin gene (HJV;
      also called HFE2) (Papanikolaou, G., Samuels, M. E., Ludwig, E. H., MacDonald, M.
      L., Franchini, P. L., Dube, M. P., Andres, L., MacFarlane, J., Sakellaropoulos,
      N., Politou, M., Nemeth, E., Thompson, J., Risler, J. K., Zaborowska, C.,
      Babakaiff, R., Radomski, C. C., Pape, T. D., Davidas, O., Christakis, J.,
      Brissot, P., Lockitch, G., Ganz, T., Hayden, M. R., and Goldberg, Y. P. (2004)
      Nat. Genet. 36, 77-82), whereas Type 2B HH is caused by mutations in hepcidin.
      HJV is highly expressed in both skeletal muscle and liver. Mutations in HJV are
      implicated in the majority of diagnosed juvenile hemochromatosis patients. In
      this study, we stably transfected HJV cDNA into human embryonic kidney 293 cells
      and characterized the processing of HJV and its effect on iron homeostasis. Our
      results indicate that HJV is a glycosylphosphatidylinositol-linked protein and
      undergoes a partial autocatalytic cleavage during its intracellular processing.
      HJV co-immunoprecipitated with neogenin, a receptor involved in a variety of
      cellular signaling processes. It did not interact with the closely related
      receptor DCC (deleted in Colon Cancer). In addition, the HJV G320V mutant
      implicated in Type 2A HH did not co-immunoprecipitate with neogenin. Immunoblot
      analysis of ferritin levels and transferrin-55Fe accumulation studies indicated
      that the HJV-induced increase in intracellular iron levels in human embryonic
      kidney 293 cells is dependent on the presence of neogenin in the cells, thus
      linking these two proteins to intracellular iron homeostasis.

PMID- 16103118
TI  - IkappaB kinase alpha regulates subcellular distribution and turnover of cyclin D1
      by phosphorylation.
AB  - IkappaB kinases (IKKs), IKKalpha and IKKbeta, with a regulatory subunit
      IKKgamma/NEMO constitute a high molecular weight IKK complex that regulates NF
      kappaB activity. Although IKKalpha and IKKbeta share structural and biochemical
      similarities, IKKalpha has been shown to have distinct biological roles. Here we
      show that IKKalpha plays a critical role in regulating cyclin D1 during the cell
      cycle. Analysis of IKKalpha-/- mouse embryo fibroblast cells showed that cyclin
      D1 is overexpressed and localized in the nucleus compared with parental mouse
      embryo fibroblasts. IKKalpha associates with and phosphorylates cyclin D1.
      Analysis on cyclin D1 mutants demonstrated that IKKalpha phosphorylates cyclin D1
      at Thr286. Reconstitution of IKKalpha in knockout cells leads to nuclear export
      and increased degradation of cyclin D1. Further, RNAi-mediated knockdown of
      IKKalpha results in similar changes as observed in IKKalpha-/- cells. These
      results suggest a novel role of IKKalpha in regulating subcellular localization
      and proteolysis of cyclin D1 by phosphorylation of cyclin D1 at Thr286, the same
      residue earlier found to be a target for glycogen synthase kinase-3beta-induced
      phosphorylation.

PMID- 16103119
TI  - Uncoupling ligand-dependent and -independent mechanisms for mitogen-activated
      protein kinase activation by the murine Ron receptor tyrosine kinase.
AB  - Receptor tyrosine kinases (RTKs) activate downstream signaling through cognate
      growth factor receptor-induced dimerization and autophosphorylation.
      Overexpression of RTKs can lead to constitutive activation due to increased
      dimerization in the absence of ligand, and downstream signals are presumed to be
      the same as the ligand-induced signals. We have shown that the murine Ron (mRon)
      receptor tyrosine kinase exhibits constitutive activation of the MAP kinase
      pathway that is independent of the two docking site tyrosines, whereas activation
      of this pathway in response to ligand (macrophage-stimulating protein) is
      abolished in the absence of these tyrosines. Furthermore, we identified three
      tyrosines (Tyr-1175, Tyr-1265, and Tyr-1294) within the kinase domain that play
      critical but overlapping roles in controlling constitutive Erk activation by
      mRon. Phenylalanine mutations at these three tyrosines results in a receptor that
      fails to constitutively activate the Erk pathway but retains the ability to
      induce Erk phosphorylation in response to ligand stimulation. The ability of mRon
      to activate the MAP kinase pathway is dependent on c-Src activity, and we have
      shown that c-Src co-immunoprecipitates with mRon. c-Src fails to interact with
      mRon when the three tyrosines required for MAP kinase activation are mutated,
      whereas the presence of any one of these tyrosines alone restores Erk
      phosphorylation and recruitment of c-Src. Thus, the ligand-dependent and 
      independent activity of mRon can be uncoupled through the alteration of selective
      sets of tyrosines.

PMID- 16103120
TI  - A specific microdomain ("glycosynapse 3") controls phenotypic conversion and
      reversion of bladder cancer cells through GM3-mediated interaction of alpha3beta1
      integrin with CD9.
AB  - Cell motility is highly dependent on the organization and function of
      microdomains composed of integrin, proteolipid/tetraspanin CD9, and ganglioside
      (Ono, M., Handa, K., Sonnino, S., Withers, D. A., Nagai, H., and Hakomori, S.
      (2001) Biochemistry 40, 6414-6421; Kawakami, Y., Kawakami, K., Steelant, W. F.
      A., Ono, M., Baek, R. C., Handa, K., Withers, D. A., and Hakomori, S. (2002) J.
      Biol. Chem. 277, 34349-34358), later termed "glycosynapse 3" (Hakomori, S., and
      Handa, K. (2002) FEBS Lett. 531, 88-92, 2002). Human bladder cancer cell lines
      KK47 (noninvasive and nonmetastatic) and YTS1 (highly invasive and metastatic),
      both derived from transitional bladder epithelia, are very similar in terms of
      integrin composition and levels of tetraspanin CD9. Tetraspanin CD82 is absent in
      both. The major difference is in the level of ganglioside GM3, which is several
      times higher in KK47 than in YTS1. We now report that the GM3 level reflects
      glycosynapse function as follows: (i) a stronger interaction of integrin alpha3
      with CD9 in KK47 than in YTS1; (ii) conversion of benign, low motility KK47 to
      invasive, high motility cells by depletion of GM3 by P4 (D-threo-1-phenyl-2
      palmitoylamino-3-pyrrolidino-1-propanol) treatment or by knockdown of CD9 by the
      RNA interference method; (iii) reversion of high motility YTS1 to low motility
      phenotype like that of KK47 by exogenous GM3 addition, whereby the alpha3-to-CD9
      interaction was enhanced; (iv) low GM3 level activated c-Src in YTS1 or in P4
      treated KK47, and high GM3 level by exogenous addition caused Csk translocation
      into glycosynapse, with subsequent inhibition of c-Src activation; (v) inhibition
      of c-Src by "PP2" in YTS1 greatly reduced cell motility. Thus, GM3 in
      glycosynapse 3 plays a dual role in defining glycosynapse 3 function. One is by
      modulating the interaction of alpha3 with CD9; the other is by activating or
      inhibiting the c-Src activity, possibly through Csk translocation. High GM3 level
      decreases tumor cell motility/invasiveness, whereas low GM3 level enhances tumor
      cell motility/invasiveness. Oncogenic transformation and its reversion can be
      explained through the difference in glycosynapse organization.

PMID- 16103121
TI  - The switch in alternative splicing of cyclic AMP-response element modulator
      protein CREM{tau}2{alpha} (activator) to CREM{alpha} (repressor) in human
      myometrial cells is mediated by SRp40.
AB  - The transcription factor cAMP-response element modulator (CREM) protein, plays a
      major role in cAMP-responsive gene regulation. Biological consequences resulting
      from the transcriptional stimuli of CREM are dictated by the expression of
      multiple protein isoforms generated by extensive alternative splicing of its
      precursor mRNA. We have previously shown that alternative splicing enables the
      expression of the CREM gene to be "switched" within the human myometrium during
      pregnancy from the production of CREMtau(2alpha), a potent transcriptional
      activator to the synthesis of CREMalpha, a transcriptional repressor. Furthermore
      we have recently reported that this change in the expression of CREM spliced
      variants is likely to have important ramifications on the regulation of
      downstream cAMP-response element-responsive target genes involved in uterine
      activity during gestation. We have investigated the splicing factors involved in
      controlling the expression of myometrial CREM splice variants. Data presented
      here from transient transfections indicate that the switch in the synthesis of
      CREMtau(2)alpha to CREMalpha that occurs during pregnancy is regulated primarily
      by an SR protein family member, SRp40. We also show that expression of this
      splicing factor is tightly regulated in the myometrium during pregnancy. SRp40
      regulates the splicing of CREM via its interactions with multiple ESE motifs
      present in the alternatively exons of CREM. In vitro splicing and electrophoretic
      mobility shift assays were employed to confirm the functionality of the SRp40
      binding ESEs, thus providing a mechanistic explanation of how SRp40 regulates the
      switch in splicing from production of CREMtau(2)alpha to CREMalpha.

PMID- 16103122
TI  - A switch 3 point mutation in the alpha subunit of transducin yields a unique
      dominant-negative inhibitor.
AB  - The rhodopsin/transducin-coupled vertebrate vision system has served as a
      paradigm for G protein-coupled signaling. We have taken advantage of this system
      to identify new types of constitutively active, transducin-alpha (alphaT)
      subunits. Here we have described a novel dominant-negative mutation, made in the
      background of a chimera consisting of alphaT and the alpha subunit of G(i1)
      (designated alphaT*), which involves the substitution of a conserved arginine
      residue in the conformationally sensitive Switch 3 region. Changing Arg-238 to
      either lysine or alanine had little or no effect on the ability of alphaT* to
      undergo rhodopsin-stimulated GDP-GTP exchange, whereas substituting glutamic acid
      for arginine at this position yielded an alphaT* subunit (alphaT*(R238E)) that
      was incapable of undergoing rhodopsin-dependent nucleotide exchange and was
      unable to bind or stimulate the target/effector enzyme (cyclic GMP
      phosphodiesterase). Moreover, unlike the GDP-bound forms of alphaT*,
      alphaT*(R238A) and alphaT*(R238K), the alphaT*(R238E) mutant did not respond to
      aluminum fluoride (AlF4(-)), as read out by changes in Trp-207 fluorescence.
      However, surprisingly, we found that alphaT*(R238E) effectively blocked rhodopsin
      catalyzed GDP-GTP exchange on alphaT*, as well as rhodopsin-stimulated
      phosphodiesterase activity. Analysis by high pressure liquid chromatography
      indicated that the alphaT*(R238E) mutant exists in a nucleotide-free state.
      Nucleotide-free forms of G alpha subunits were typically very sensitive to
      proteolytic degradation, but alphaT*(R238E) exhibited a resistance to trypsin
      proteolysis similar to that observed with activated forms of alphaT*. Overall,
      these findings indicated that by mutating a single residue in Switch 3, it is
      possible to generate a unique type of dominant-negative G alpha subunit that can
      effectively block signaling by G protein-coupled receptors.

PMID- 16103123
TI  - Gamma-secretase is a functional component of phagosomes.
AB  - Gamma-secretase is a high molecular mass protein complex that catalyzes the
      intramembrane cleavage of its protein substrates. Two proteins involved in
      phagocytosis, CD44 and the low density lipoprotein receptor-related protein, are
      gamma-secretase substrates, suggesting that this complex might regulate some
      aspects of phagocytosis. Our results indicate that the four components of gamma
      secretase, viz. presenilin, nicastrin, APH-1, and PEN-2, are present and enriched
      on phagosome membranes from both murine macrophages and Drosophila S2 phagocytes.
      The gamma-secretase components form high molecular mass complexes in lipid
      microdomains of the phagosome membrane with the topology expected for the
      functional enzyme. In contrast to the majority of the phagosome proteins studied
      so far, which appear to associate transiently with this organelle, gamma
      secretase resides on newly formed phagosomes and remains associated throughout
      their maturation into phagolysosomes. Finally, our results indicate that
      interferon-gamma stimulates gamma-secretase-dependent cleavages on phagosomes and
      that gamma-secretase activity may be involved in the phagocytic response of
      macrophages to inflammatory cytokines.

PMID- 16103124
TI  - A {gamma}-secretase-independent mechanism of signal transduction by the amyloid
      precursor protein.
AB  - It has been proposed that gamma-secretase-mediated release of the amyloid
      precursor protein (APP) intracellular domain (AICD) results in nuclear
      translocation and signaling through a complex with the adaptor protein Fe65 and
      the histone acetyltransferase Tip60. Here, we show that APP and Fe65 activate
      transcription through a Gal4-Tip60 reporter in presenilin-1/2-deficient cells
      lacking generation of AICD. APP and Fe65 also activated transcription in the
      presence of gamma-secretase inhibitors that prevent amyloid beta-peptide
      production in human embryonic kidney 293 and SH-SY5Y cells. In contrast to the
      transcriptionally active Notch intracellular domain, expression of AICD did not
      activate transcription. An alternative mechanism for APP signal transduction is
      suggested by the identification of essential cyclin-dependent kinase (CDK)
      phosphorylation sites in Tip60. Mutation of these Tip60 phosphorylation sites or
      treatment with the CDK inhibitor roscovitine blocked the ability of APP to signal
      through Tip60. Moreover, APP stabilized Tip60 through CDK-dependent
      phosphorylation. Subcellular fractionation and confocal immunofluorescence showed
      that APP recruited Tip60 to membrane compartments. Thus, APP may signal to the
      nucleus by a gamma-secretase-independent mechanism that involves membrane
      sequestration and phosphorylation of Tip60.

PMID- 16103125
TI  - Structure and lytic activity of a Bacillus anthracis prophage endolysin.
AB  - We report a structural and functional analysis of the lambda prophage Ba02
      endolysin (PlyL) encoded by the Bacillus anthracis genome. We show that PlyL
      comprises two autonomously folded domains, an N-terminal catalytic domain and a C
      terminal cell wall-binding domain. We determined the crystal structure of the
      catalytic domain; its three-dimensional fold is related to that of the cell wall
      amidase, T7 lysozyme, and contains a conserved zinc coordination site and other
      components of the catalytic machinery. We demonstrate that PlyL is an N
      acetylmuramoyl-L-alanine amidase that cleaves the cell wall of several Bacillus
      species when applied exogenously. We show, unexpectedly, that the catalytic
      domain of PlyL cleaves more efficiently than the full-length protein, except in
      the case of Bacillus cereus, and using GFP-tagged cell wall-binding domain, we
      detected strong binding of the cell wall-binding domain to B. cereus but not to
      other species tested. We further show that a related endolysin (Ply21) from the
      B. cereus phage, TP21, shows a similar pattern of behavior. To explain these
      data, and the species specificity of PlyL, we propose that the C-terminal domain
      inhibits the activity of the catalytic domain through intramolecular interactions
      that are relieved upon binding of the C-terminal domain to the cell wall.
      Furthermore, our data show that (when applied exogenously) targeting of the
      enzyme to the cell wall is not a prerequisite of its lytic activity, which is
      inherently high. These results may have broad implications for the design of
      endolysins as therapeutic agents.

PMID- 16103126
TI  - Identification of hepatocyte growth factor activator inhibitor-1B as a potential
      physiological inhibitor of prostasin.
AB  - Prostasin is a trypsin-like serine protease that is glycosylphosphatidylinositol
      anchored to the epithelial cell surface, from where it can be released in a
      soluble form. We undertook a co-expression search using the Genesis Enterprise
      System Database from Gene Logic to identify prostasin inhibitors, on the
      assumption that prostasin and its natural inhibitors may have a similar gene
      expression pattern. We found the expression profile of prostasin in normal human
      tissues to correlate highly with hepatocyte growth factor activator inhibitor-1B
      (HAI-1B) and its splice variant HAI-1. Soluble HAI-1B (sHAI-1B), comprising the
      entire extracellular domain, formed a 1:1 complex with purified prostasin in
      protein binding assays and inhibited prostasin enzymatic activity with an IC(50)
      of 66 +/- 15 nM. Two sHAI-1B mutants with inactivated N- and C-terminal Kunitz
      domains (KD1 and KD2) were used to show that the interaction of sHAI-1B with
      prostasin is mediated by KD1. In agreement, KD1 (Thr(246)-Val(303)) alone
      potently inhibited prostasin activity (IC(50) = 4.7 +/- 0.5 nM). Furthermore,
      prostasin was isolated with two major HAI-1/1B fragments (40 and 58 kDa) from
      OVCAR3 cell medium, demonstrating that prostasin.HAI-1/1B complexes are formed
      naturally. Moreover, when prostasin and HAI-1B were co-expressed in Chinese
      hamster ovary cells, complexes of prostasin with HAI-1B were detected on the cell
      membrane as well as in the culture medium, suggesting that preformed complexes
      were shed from the cell surface. The identification of HAI-1B as a potential
      physiological regulator of prostasin function, as described herein, may further
      the investigation of the role of prostasin in normal physiology and cancer.

PMID- 16103127
TI  - beta-amyloid is different in normal aging and in Alzheimer disease.
AB  - The mechanism of neurodegeneration caused by beta-amyloid in Alzheimer disease is
      controversial. Neuronal toxicity is exerted mostly by various species of soluble
      beta-amyloid oligomers that differ in their N- and C-terminal domains. However,
      abundant accumulation of beta-amyloid also occurs in the brains of cognitively
      normal elderly people, in the absence of obvious neuronal dysfunction. We
      postulated that neuronal toxicity depends on the molecular composition, rather
      than the amount, of the soluble beta-amyloid oligomers. Here we show that soluble
      beta-amyloid aggregates that accumulate in Alzheimer disease are different from
      those of normal aging in regard to the composition as well as the aggregation and
      toxicity properties.

PMID- 16103128
TI  - Endoplasmic reticulum stress compromises the ubiquitin-proteasome system.
AB  - The presence of endoplasmic reticulum (ER) stress and impaired ubiquitin
      proteasome system (UPS) activity has been independently implicated in the
      pathophysiology of conformational diseases. Here, we reveal a link between ER
      stress and the functionality of the UPS. Treatment of cells with different ER
      stressors delayed the degradation of an ER reporter substrate and caused a subtle
      but consistent accumulation of three independent nuclear/cytosolic UPS reporter
      substrates. A similar signature increase was observed upon induction of ER stress
      in transgenic mice expressing a reporter substrate. Cells undergoing ER stress
      failed to clear efficiently UBB+1, an aberrant ubiquitin found in conformational
      diseases, which in turn caused general impairment of the UPS. We conclude that ER
      stress has a general inhibitory effect on the UPS. The compromised UPS during ER
      stress may explain the long-term gradual accumulation of misfolded proteins as
      well as the selective vulnerability of particular cell populations in
      conformational diseases.

PMID- 16103129
TI  - ABCA4 mutations causing mislocalization are found frequently in patients with
      severe retinal dystrophies.
AB  - ABCA4, also called ABCR, is a retinal-specific member of the ATP-binding cassette
      (ABC) family that functions in photoreceptor outer segments as a flipase of all
      trans retinal. Homozygous and compound heterozygous ABCA4 mutations are
      associated with various autosomal recessive retinal dystrophies, whereas
      heterozygous ABCA4 mutations have been associated with dominant susceptibility to
      age-related macular degeneration in both humans and mice. We analyzed a cohort of
      29 arRP families for the mutations in ABCA4 with a commercial microarray, ABCR
      400 in addition to direct sequencing and segregation analysis, and identified
      both mutant alleles in two families (7%): compound heterozygosity for missense
      (R602W) and nonsense (R408X) alleles and homozygosity for a complex [L541P;
      A1038V] allele. The missense mutations were analyzed functionally in the
      photoreceptors of Xenopus laevis tadpoles, which revealed mislocalization of
      ABCA4 protein. These mutations cause retention of ABCA4 in the photoreceptor
      inner segment, likely by impairing correct folding, resulting in the total
      absence of physiologic protein function. Patients with different retinal
      dystrophies harboring two misfolding alleles exhibit early age-of-onset (AO) (5
      12 years) of retinal disease. Our data suggest that a class of ABCA4 mutants may
      be an important determinant of the AO of disease.

PMID- 16103130
TI  - A comparison of tagging methods and their tagging space.
AB  - Single-nucleotide polymorphism (SNP) tagging is widely used as a way of saving
      genotyping costs in association studies. A number of different tagging methods
      have been developed to reduce the number of markers to be genotyped while
      maintaining power for detecting effects on non-assayed SNPs. How the different
      methods perform in different settings, the degree to which they overlap and share
      common tags and how they differ are important questions. We investigated these
      questions by comparing three widely used tagging methods/algorithms--one
      haplotype r2-based method, one pair-wise r2-based method and one method which was
      based on haplotype diversity but focused on major haplotypes. Tagging efficiency
      was defined as the number of genotyped markers divided by the number of tagging
      SNPs. Tagging effectiveness was defined as the proportion of un-genotyped or
      'hidden' SNPs being detected (having a pair-wise or haplotype r2 with a set of
      tagging SNPs over a threshold, e.g. haplotype r2> or =0.80). The ENCODE regions
      genotyped on the HapMap CEPH individuals were examined in this study. Tagging
      effectiveness was generally poor for rare SNPs than for common SNPs, for all
      three tagging methods. Inclusion of rare SNPs into initial HapMap scheme could
      enhance the performance of tags on rare hidden SNPs at the expense of increased
      genotyping cost. At a moderate tagging efficiency, more than 90% of hidden SNPs
      detected by tagging SNPs selected by one method were also detected by tagging
      SNPs selected by another method, and this figure could be increased to 100% if
      tagging efficiency was allowed to drop. These results indicate that the tagging
      space is highly concordant between different tagging methods, despite the fact
      that they often involve different sets of tagging SNPs.

PMID- 16103131
TI  - Mice lacking COX10 in skeletal muscle recapitulate the phenotype of progressive
      mitochondrial myopathies associated with cytochrome c oxidase deficiency.
AB  - We have created a mouse model with an isolated cytochrome c oxidase (COX)
      deficiency by disrupting the COX10 gene in skeletal muscle. Missense mutations in
      COX10 have been previously associated with mitochondrial disorders. Cox10p is a
      protoheme:heme-O-farnesyl transferase required for the synthesis of heme a, the
      prosthetic group of the catalytic center of COX. COX10 conditional knockout mice
      were generated by crossing a LoxP-tagged COX10 mouse with a transgenic mouse
      expressing cre recombinase under the myosin light chain 1f promoter. The COX10
      knockout mice were healthy until approximately 3 months of age when they started
      developing a slowly progressive myopathy. Surprisingly, even though COX activity
      in COX10 KO muscles was <5% of control muscle at 2.5 months, these muscles were
      still able to contract at 80-100% of control maximal forces and showed only a 10%
      increase in fatigability, and no signs of oxidative damage or apoptosis were
      detected. However, the myopathy worsened with time, particularly in female
      animals. This COX10 KO mouse allowed us to correlate the muscle function with
      residual COX activity, an estimate that can help predict the progression pattern
      of human mitochondrial myopathies.

PMID- 16103132
TI  - DNA-dependent conversion of Oct-1 and Oct-2 into transcriptional repressors by
      Groucho/TLE.
AB  - POU domain proteins contain a bipartite DNA-binding element that can confer
      allosteric control of coactivator recruitment. Dimerization of Oct-1 and Oct-2 on
      palindromic response elements results in the conformational dependent inclusion
      or exclusion of the transcriptional coactivator OBF-1. In this paper, we
      demonstrate that Oct-1 and Oct-2 can function as transcriptional repressors by
      recruiting and physically interacting with members of the Grg/TLE family of
      corepressors. In accordance with a model of DNA induced cofactor assembly, and
      analogous to the recruitment of the OBF-1 coactivator, the different Grg/TLE
      members can discriminate between both Oct-1 and Oct-2, and the monomeric or
      dimeric nature of the POU/DNA complex.

PMID- 16103133
TI  - A revised nomenclature for mammalian acyl-CoA thioesterases/hydrolases.
AB  - Acyl-CoA thioesterases, also known as acyl-CoA hydrolases, are a group of enzymes
      that hydrolyze CoA esters such as acyl-CoAs (saturated, unsaturated, branched
      chain), bile acid-CoAs, CoA esters of prostaglandins, etc., to the corresponding
      free acid and CoA. However, there is significant confusion regarding the
      nomenclature of these genes. In agreement with the HUGO Gene Nomenclature
      Committee and the Mouse Genomic Nomenclature Committee, a revised nomenclature
      for mammalian acyl-CoA thioesterases/hydrolases has been suggested for the 12
      member family. The family root symbol is ACOT, with human genes named ACOT1
      ACOT12, and rat and mouse genes named Acot1-Acot12. Several of the ACOT genes are
      the result of splicing events, and these splice variants are cataloged.

PMID- 16103134
TI  - Relative contributions of the five major human cytochromes P450, 1A2, 2C9, 2C19,
      2D6, and 3A4, to the hepatic metabolism of the proteasome inhibitor bortezomib.
AB  - VELCADE (bortezomib, PS-341), reversibly inhibits the 20S proteasome and exhibits
      cytotoxic and antitumor activities. Pretreatment of cancer cells with bortezomib
      increases the chemosensitivity of these cells, suggesting that bortezomib may be
      used in combination chemotherapy. The relative contributions of the five major
      human cytochromes P450 (P450s), 1A2, 2C9, 2C19, 2D6, and 3A4 (the focus of the
      present study), to the metabolism of bortezomib are an important aspect of
      potential drug interactions. Relative activity factor (RAF), chemical inhibition,
      and immunoinhibition using monoclonal antibodies were three approaches employed
      to determine the relative contributions of the major human P450s to the net
      hepatic metabolism of bortezomib. RAFs for the P450 isoform-selective substrates
      were determined; the ratio of the rate of metabolism of bortezomib with cDNA
      expressed P450s versus rate of metabolism with human liver microsomes was
      normalized with respect to the RAF for each P450 isoform to determine the
      percentage contributions of the P450s to the net hepatic metabolism of
      bortezomib. CYP3A4 followed by CYP2C19 were determined to be the major
      contributors to the metabolism of bortezomib. Chemical inhibition and
      immunoinhibition confirmed that CYP3A4 and CYP2C19 were the major P450s
      responsible for the hepatic metabolism of bortezomib. The studies were conducted
      with 2 muM bortezomib, and the disappearance of bortezomib, rather than
      appearance of a specific metabolite, was quantified to determine the
      contributions of the P450s to the overall hepatic metabolism of bortezomib in
      humans.

PMID- 16103135
TI  - Quantitation of bisphenol A and bisphenol A glucuronide in biological samples by
      high performance liquid chromatography-tandem mass spectrometry.
AB  - Bisphenol A (BPA) is a weak estrogen. Pharmacokinetic studies of BPA have
      demonstrated a rapid and extensive metabolism of BPA to the nonestrogenic BPA
      monoglucuronide (BPA-gluc). Some investigators have reported that BPA was found
      at parts per billion concentrations in the tissues or urine of humans without
      known exposure to BPA. This work developed a rapid and sensitive method for the
      determination of BPA and BPA-gluc in plasma and urine based on liquid
      chromatography-tandem mass spectrometry. The liquid chromatography-electrospray
      ionization-tandem mass spectrometry method for quantitation of BPA and BPA-gluc
      uses stable isotope-labeled internal standards. A linear ion trap mass
      spectrometer permits identification and quantitation of BPA-gluc and BPA without
      sample workup. Development of separation conditions reduced the BPA-background in
      solvent samples to below 2.5 pmol/ml for BPA. Limit of quantitation (LOQ) for BPA
      in control urine was 15 pmol/ml; LOQ for BPA-gluc was 65 pmol/ml. Application of
      the method to urine samples from human subjects (n = 6) after administration of
      25 microg of BPA/person (estimated maximum human daily intake) permitted the
      determination of excretion kinetics for BPA-gluc; BPA was below the LOD in all
      except two of the samples. In urine or blood samples of human subjects (n = 19)
      without intentional exposure to BPA, BPA concentrations were always below the
      limit of detection ( approximately 2.5 pmol/ml) with or without prior
      glucuronidase treatment. The results show that care is required for analysis of
      BPA and its major metabolite BPA-gluc. The LOD obtained and the absence of
      detectable levels of BPA in samples from individuals suggests that general
      exposure of humans to BPA is much lower than the worst-case exposure scenario
      developed.

PMID- 16103137
TI  - Tetraspanins in viral infections: a fundamental role in viral biology?

PMID- 16103138
TI  - Key Golgi factors for structural and functional maturation of bunyamwera virus.
AB  - Several complex enveloped viruses assemble in the membranes of the secretory
      pathway, such as the Golgi apparatus. Among them, bunyaviruses form immature
      viral particles that change their structure in a trans-Golgi-dependent manner. To
      identify key Golgi factors for viral structural maturation, we have purified and
      characterized the three viral forms assembled in infected cells, two
      intracellular intermediates and the extracellular mature virion. The first viral
      form is a pleomorphic structure with fully endo-beta-N-acetylglucosaminidase H
      (Endo-H)-sensitive, nonsialylated glycoproteins. The second viral intermediate is
      a structure with hexagonal and pentagonal contours and partially Endo-H-resistant
      glycoproteins. Sialic acid is incorporated into the small glycoprotein of this
      second viral form. Growing the virus in glycosylation-deficient cells confirmed
      that acquisition of Endo-H resistance but not sialylation is critical for the
      trans-Golgi-dependent structural maturation and release of mature viruses.
      Conformational changes in viral glycoproteins triggered by changes in sugar
      composition would then induce the assembly of a compact viral particle of angular
      contours. These structures would be competent for the second maturation step,
      taking place during exit from cells, that originates fully infectious virions.

PMID- 16103139
TI  - High-level expression of single-chain Fv-Fc fusion protein in serum and egg white
      of genetically manipulated chickens by using a retroviral vector.
AB  - We report here the generation of transgenic chickens using a retroviral vector
      for the production of recombinant proteins. It was found that the transgene
      expression was suppressed when a Moloney murine leukemia virus-based retroviral
      vector was injected into chicken embryos at the blastodermal stage. When a
      concentrated viral solution was injected into the heart of developing embryos
      after 50 to 60 h of incubation, transgene expression was observed throughout the
      embryo, including the gonads. For practical production, a retroviral vector
      encoding an expression cassette of antiprion single-chain Fv fused with the Fc
      region of human immunoglobulin G1 (scFv-Fc) was injected into chicken embryos.
      The birds that hatched stably produced scFv-Fc in their serum and eggs at high
      levels (approximately 5.6 mg/ml). We obtained transgenic progeny from a
      transgenic chicken generated with this procedure. The transgene was stably
      integrated into the chromosomes of transgenic progeny. The transgenic progeny
      also expressed scFv-Fc in the serum and eggs.

PMID- 16103140
TI  - Neuron-to-cell spread of pseudorabies virus in a compartmented neuronal culture
      system.
AB  - Alphaherpesviruses are parasites of the peripheral nervous system in their
      natural hosts. After the initial infection of peripheral tissues such as mucosal
      cells, these neurotropic viruses will invade the peripheral nervous system that
      innervates the site of infection via long-distance axonal transport of the viral
      genome. In natural hosts, a latent and a nonproductive infection is usually
      established in the neuronal cell bodies. Upon reactivation, the newly replicated
      genome will be assembled into capsids and transported back to the site of entry,
      where a localized infection of the epithelial or mucosal cells will produce
      infectious virions that can infect naive hosts. In this paper, we describe an in
      vitro method for studying neuron-to-cell spread of alphaherpesviruses using a
      compartmented culture system. Using pseudorabies virus as a model, we infected
      neuron cell bodies grown in Teflon chambers and observed spread of infection to
      nonneuronal cells plated in a different compartment. The cells are in contact
      with the neurons via axons that penetrate the Teflon barrier. We demonstrate that
      wild-type neuron-to-cell spread requires intact axons and the presence of gE, gI,
      and Us9 proteins, but does not require gD. We also provide ultrastructural
      evidence showing that capsids enclosed within vesicles can be found along the
      entire length of the axon during viral egress.

PMID- 16103141
TI  - Human endogenous retrovirus expression profiles in samples from brains of
      patients with schizophrenia and bipolar disorders.
AB  - The detection and identification of retroviral transcripts in brain samples,
      cerebrospinal fluid, and plasma of individuals with recent-onset schizophrenia
      and schizoaffective disorders suggest that activation or upregulation of distinct
      human endogenous retroviruses (HERVs) may play a role in the etiopathogenesis of
      neuropsychiatric diseases. To test this hypothesis, we performed a comprehensive
      microarray-based analysis of HERV transcriptional activity in human brains. We
      investigated 50 representative members of 20 HERV families in a total of 215
      brain samples derived from individuals with schizophrenia or bipolar disorders
      and matched controls. A characteristic brain-specific retroviral activity profile
      was found that consists of members of the class I families HERV-E, HERV-F, and
      ERV9 and members of HERV-K taxa. In addition to these constitutively expressed
      HERVs, a number of differentially active HERV elements were identified in all
      brain samples independent of the disease pattern that may reflect differences in
      the genetic background of the tested individuals. Only a subgroup of the HML-2
      family (HERV-K10) was significantly overrepresented in both bipolar-disorder- and
      schizophrenia-associated samples compared to healthy brains, suggesting a
      potential association with disease. Real-time PCR analysis of HERV env
      transcripts with coding capacity potentially involved in neuroinflammatory
      conditions revealed that env expression of HERV-W, HERV-FRD, and HML-2 remains
      unaffected regardless of the clinical picture. Our data suggest that HERV
      transcription in brains is weakly correlated with schizophrenia and related
      diseases but may be influenced by the individual genetic background, brain
      infiltrating immune cells, or medical treatment.

PMID- 16103142
TI  - Biochemical and immunogenic characterization of soluble human immunodeficiency
      virus type 1 envelope glycoprotein trimers expressed by semliki forest virus.
AB  - The current lack of envelope glycoprotein immunogens that elicit broadly
      neutralizing antibody responses remains a major challenge for human
      immunodeficiency virus type 1 (HIV-1) vaccine development. However, the recent
      design and construction of stable soluble gp140 trimers have shown that some
      neutralization breadth can be achieved by using immunogens that better mimic the
      functional viral spike complex. The use of genetic delivery systems to drive the
      in vivo expression of such immunogens for the stimulation of neutralizing
      antibodies against HIV-1 may offer advantages by maintaining the quaternary
      structure of the trimeric envelope glycoproteins. Here, we describe the
      biochemical and immunogenic properties of soluble HIV-1 envelope glycoprotein
      trimers expressed by recombinant Semliki Forest virus (rSFV). The results
      presented here demonstrate that rSFV supports the expression of stable soluble
      gp140 trimers that retain recognition by conformationally sensitive antibodies.
      Further, we show that rSFV particle immunizations efficiently primed immune
      responses as measured after a single boost with purified trimeric gp140 protein,
      resulting in a Th1-biased antibody response. This differed from the Th2-biased
      antibody response obtained after repeated immunizations with purified gp140
      protein trimers. Despite this difference, both regimens stimulated neutralizing
      antibody responses of similar potency. This suggests that rSFV may be a useful
      component of a viral vector prime-protein boost regimen aimed at stimulating both
      cell-mediated immune responses and neutralizing antibodies against HIV-1.

PMID- 16103143
TI  - Identification of domains in Autographa californica multiple nucleopolyhedrovirus
      late expression factor 3 required for nuclear transport of P143.
AB  - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) late expression
      factor 3 (LEF-3) is an essential protein for DNA replication in transient assays.
      P143, a large DNA-binding protein with DNA-unwinding activity, is also essential
      for viral DNA replication in vivo. Both LEF-3 and P143 are found in the nucleus
      of AcMNPV-infected cells, but only LEF-3 localizes to the nucleus when expressed
      in transfected cells on its own from a plasmid expression vector. P143 requires
      LEF-3 as a transporter to enter the nucleus. To investigate the possibility that
      LEF-3 carries a nuclear localization signal domain, we constructed a series of
      LEF-3 deletion mutants and examined the intracellular localization of the
      products in plasmid-transfected cells. We discovered that the N-terminal 56 amino
      acid residues of LEF-3 were sufficient for nuclear localization and that this
      domain, when fused with either the green fluorescent protein reporter gene or
      P143, was able to direct these proteins to the nucleus. Transient DNA replication
      assays demonstrated that fusing the LEF-3 nuclear localization signal domain to
      P143 did not alter the function of P143 in supporting DNA replication but was not
      sufficient to substitute for whole LEF-3. These data show that although one role
      for LEF-3 during virus infection is to transport P143 to the nucleus, LEF-3
      performs other essential replication functions once inside the nucleus.

PMID- 16103144
TI  - Mutations of Epstein-Barr virus gH that are differentially able to support fusion
      with B cells or epithelial cells.
AB  - The core fusion machinery of all herpesviruses consists of three conserved
      glycoproteins, gB and gHgL, suggesting a common mechanism for virus cell fusion,
      but fusion of Epstein-Barr virus (EBV) with B cells and epithelial cells is
      initiated differently. Fusion with B cells requires a fourth protein, gp42, which
      complexes with gHgL and interacts with HLA class II, the B-cell coreceptor.
      Fusion with an epithelial cell does not require gp42 but requires interaction of
      gHgL with a novel epithelial cell coreceptor. Epithelial cell fusion can be
      inhibited by gp42 binding to gHgL and by antibodies to gH that fail to block B
      cell fusion. This suggests that regions of gHgL initiating fusion with each cell
      are separable from each other and from regions involved in fusion itself. To
      address this possibility we mapped the region of gH recognized by a monoclonal
      antibody to gH that blocks EBV fusion with epithelial cells but not B cells by
      making a series of chimeras with the gH homolog of rhesus lymphocryptovirus.
      Proteins with mutations engineered within this region included those that
      preferentially mediate fusion with B cells, those that preferentially mediate
      fusion with epithelial cells, and those that mediate fusion with neither cell
      type. These results support the hypothesis that the core fusion function of gH is
      the same for B cells and epithelial cells and that it differs only in the way in
      which it is triggered into a functionally active state.

PMID- 16103145
TI  - Structural determinants of tissue tropism and in vivo pathogenicity for the
      parvovirus minute virus of mice.
AB  - Two strains of the parvovirus minute virus of mice (MVM), the immunosuppressive
      (MVMi) and the prototype (MVMp) strains, display disparate in vitro tropism and
      in vivo pathogenicity. We report the crystal structures of MVMp virus-like
      particles (MVMp(b)) and native wild-type (wt) empty capsids (MVMp(e)), determined
      and refined to 3.25 and 3.75 A resolution, respectively, and their comparison to
      the structure of MVMi, also refined to 3.5 A resolution in this study. A
      comparison of the MVMp(b) and MVMp(e) capsids showed their structures to be the
      same, providing structural verification that some heterologously expressed
      parvovirus capsids are indistinguishable from wt capsids produced in host cells.
      The structures of MVMi and MVMp capsids were almost identical, but local surface
      conformational differences clustered from symmetry-related capsid proteins at
      three specific domains: (i) the icosahedral fivefold axis, (ii) the "shoulder" of
      the protrusion at the icosahedral threefold axis, and (iii) the area surrounding
      the depression at the icosahedral twofold axis. The latter two domains contain
      important determinants of MVM in vitro tropism (residues 317 and 321) and forward
      mutation residues (residues 399, 460, 553, and 558) conferring fibrotropism on
      MVMi. Furthermore, these structural differences between the MVM strains
      colocalize with tropism and pathogenicity determinants mapped for other
      autonomous parvovirus capsids, highlighting the importance of common parvovirus
      capsid regions in the control of virus-host interactions.

PMID- 16103146
TI  - The cotton rat (Sigmodon hispidus) is a permissive small animal model of human
      metapneumovirus infection, pathogenesis, and protective immunity.
AB  - Human metapneumovirus (hMPV) is a newly described paramyxovirus that is an
      important cause of acute respiratory tract disease. We undertook to develop a
      small animal model of hMPV infection, pathogenesis, and protection. Hamsters,
      guinea pigs, cotton rats, and nine inbred strains of mice were inoculated
      intranasally with hMPV. The animals were sacrificed, and nasal and lung tissue
      virus yields were determined by plaque titration. None of the animals exhibited
      respiratory symptoms. The quantity of virus present in the nasal tissue ranged
      from 4.6 x 10(2) PFU/gram tissue (C3H mice) to greater than 10(5) PFU/gram
      (hamster). The amount of virus in the lungs was considerably less than in nasal
      tissue in each species tested, ranging from undetectable (<5 PFU/g; guinea pigs)
      to 1.8 x 10(5) PFU/gram (cotton rat). The peak virus titer in cotton rat lungs
      occurred on day 4 postinfection. hMPV-infected cotton rat lungs examined on day 4
      postinfection exhibited histopathological changes consisting of peribronchial
      inflammatory infiltrates. Immunohistochemical staining detected virus only at the
      luminal surfaces of respiratory epithelial cells throughout the respiratory
      tract. hMPV-infected cotton rats mounted virus-neutralizing antibody responses
      and were partially protected against virus shedding and lung pathology on
      subsequent rechallenge with hMPV. Viral antigen was undetectable in the lungs on
      challenge of previously infected animals. This study demonstrates that the cotton
      rat is a permissive small animal model of hMPV infection that exhibits lung
      histopathology associated with infection and that primary infection protected
      animals against subsequent infection. This model will allow further in vivo
      studies of hMPV pathogenesis and evaluation of vaccine candidates.

PMID- 16103147
TI  - Envelope glycoprotein gB of Kaposi's sarcoma-associated herpesvirus is essential
      for egress from infected cells.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) envelope glycoprotein gB interacts
      with cell surface heparan sulfate (HS) and alpha3beta1 integrin and plays roles
      in the initial binding and entry into the target cells and in the induction of
      preexisting host cell signal pathways. To define gB function further, using a
      bacterial artificial chromosome (BAC) system carrying the KSHV genome (BAC36wt
      KSHV), we constructed a recombinant virus genome with the gB open reading frame
      (ORF) deleted by replacing a 2-kb gB ORF with a 1.3-kb Kan(r) gene. Stable 293T
      cells carrying BAC36wt-KSHV and DeltagBBAC36-KSHV genomes were generated.
      Transcript analyses and immunoprecipitation reactions confirmed the absence of gB
      in the 293T-DeltagBBAC36 cells. When monolayers of 293T-BAC36wt and 293T
      DeltagBBAC36 cells were induced with tetradecanoylphorbol-13-acetate, infectious
      virus was detected only from the 293T-BAC36wt cell supernatants. No significant
      amount of DNase I-resistant viral DNA was detected in the supernatants of 293T
      DeltagBBAC36 cells. BAC36wt-KSHV infected the target cells, and in contrast, no
      viral DNA and transcripts could be detected in cells infected with DeltagBBAC36
      KSHV. Electron microscopy of 293T-DeltagBBAC36 cells revealed capsids in the
      nuclei, cytoplasmic vesicles with core-containing capsids, and occasional
      enveloped virions in the cytoplasm. However, enveloped virus particles were
      observed in the extracellular compartments of 293T-BAC36wt cells only and not in
      293T-DeltagBBAC36 cells. Transfection of 293T-DeltagBBAC36 cells with plasmid
      expressing full-length gB restored the recovery of infectious KSHV in the
      supernatant. These results suggest that, besides its role in virus binding and
      entry into the target cells, KSHV gB also plays a role in the maturation and
      egress of virus from the infected cells.

PMID- 16103148
TI  - Hepatitis A virus suppresses RIG-I-mediated IRF-3 activation to block induction
      of beta interferon.
AB  - Hepatitis A virus (HAV) antagonizes the innate immune response by inhibition of
      double-stranded RNA (dsRNA)-induced beta interferon (IFN-beta) gene expression.
      In this report, we show that this is due to an interaction of HAV with the
      intracellular dsRNA-induced retinoic acid-inducible gene I (RIG-I)-mediated
      signaling pathway upstream of the kinases responsible for interferon regulatory
      factor 3 (IRF-3) phosphorylation (TBK1 and IKKepsilon). In consequence, IRF-3 is
      not activated for nuclear translocation and gene induction. In addition, we found
      that HAV reduces TRIF (TIR domain-containing adaptor inducing IFN-beta)-mediated
      IRF-3 activation, which is part of the Toll-like receptor 3 signaling pathway. As
      IRF-3 is necessary for IFN-beta transcription, inhibition of this factor results
      in efficient suppression of IFN-beta synthesis. This ability of HAV seems to be
      of considerable importance for HAV replication, as HAV is not resistant to IFN
      beta, and it may allow the virus to establish infection and preserve the sites of
      virus production in later stages of the infection.

PMID- 16103149
TI  - Human immunodeficiency virus type 1 Vpr induces the degradation of the UNG and
      SMUG uracil-DNA glycosylases.
AB  - The human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr has
      previously been shown to bind to the cellular uracil DNA glycosylase UNG. We show
      here that the binding of Vpr to UNG and to the related enzyme SMUG induces their
      proteasomal degradation. UNG and SMUG were found to be encapsidated in Deltavpr
      HIV-1 virions but were significantly less abundant in vpr(+) virions. Deltavpr
      virions contained readily detectable uracil-DNA glycosylase enzymatic activity,
      while the activity was reduced to undetectable levels in vpr(+) virions.
      Consistent with proteasomal degradation, complexes that contained Vpr and the E3
      ubiquitin ligase components Cul1 and Cul4 were detected in cell lysates. We
      hypothesized that the interaction of Vpr might be a means for the virus to reduce
      the frequency of abasic sites in viral reverse transcripts at uracil residues
      caused by APOBEC3-catalyzed deamination of cytosine residues. Although APOBEC3 is
      largely neutralized by the Vif accessory protein, residual enzyme could remain in
      virions that would generate uracils. In support of this, Deltavif vpr(+) HIV-1
      produced in the presence of limited amounts of APOBEC3G was significantly more
      infectious than Deltavif Deltavpr virus. In Addition, vpr(+) HIV-1 replicated
      more efficiently than vpr(-) virus in cells that expressed limited amounts of
      APOBEC3G. The findings highlight the importance of cytidine deamination in the
      virus replication cycle and present a novel function for Vpr.

PMID- 16103150
TI  - The product of the vaccinia virus L5R gene is a fourth membrane protein encoded
      by all poxviruses that is required for cell entry and cell-cell fusion.
AB  - The L5R gene of vaccinia virus is conserved among all sequenced members of the
      Poxviridae but has no predicted function or recognized nonpoxvirus homolog. Here
      we provide the initial characterization of the L5 protein. L5 is expressed
      following DNA replication with kinetics typical of a viral late protein, contains
      a single intramolecular disulfide bond formed by the virus-encoded cytoplasmic
      redox pathway, and is incorporated into intracellular mature virus particles,
      where it is exposed on the membrane surface. To determine whether L5 is essential
      for virus replication, we constructed a mutant that synthesizes L5 only in the
      presence of an inducer. The mutant exhibited a conditional-lethal phenotype, as
      cell-to-cell virus spread and formation of infectious progeny were dependent on
      the inducer. Nevertheless, all stages of replication occurred in the absence of
      inducer and intracellular and extracellular progeny virions appeared
      morphologically normal. Noninfectious virions lacking L5 could bind to cells, but
      the cores did not enter the cytoplasm. In addition, virions lacking L5 were
      unable to mediate low-pH-triggered cell-cell fusion from within or without. The
      phenotype of the L5R conditional lethal mutant is identical to that of recently
      described mutants in which expression of the A21, A28, and H2 genes is repressed.
      Thus, L5 is the fourth component of the poxvirus cell entry/fusion apparatus that
      is required for entry of both the intracellular and extracellular infectious
      forms of vaccinia virus.

PMID- 16103151
TI  - A capsid-modified helper-dependent adenovirus vector containing the beta-globin
      locus control region displays a nonrandom integration pattern and allows stable,
      erythroid-specific gene expression.
AB  - Gene therapy for hemoglobinopathies requires efficient gene transfer into
      hematopoietic stem cells and high-level erythroid-specific gene expression.
      Toward this goal, we constructed a helper-dependent adenovirus vector carrying
      the beta-globin locus control region (LCR) to drive green fluorescent protein
      (GFP) expression, whereby the LCR-GFP cassette is flanked by adeno-associated
      virus (AAV) inverted terminal repeats (Ad.LCR-beta-GFP). This vector possesses
      the adenovirus type 35 fiber knob that allows efficient infection of
      hematopoietic cells. Transduction and vector integration studies were performed
      in MO7e cells, a growth factor-dependent CD34(+) erythroleukemic cell line, and
      in cord blood-derived human CD34(+) cells. Stable transduction of MO7e cells with
      Ad.LCR-beta-GFP was more efficient and less subject to position effects and
      silencing than transduction with a vector that did not contain the beta-globin
      LCR. Analysis of integration sites indicated that Ad.LCR-beta-GFP integration in
      MO7e cells was not random but tethered to chromosome 11, specifically to the
      globin LCR. More than 10% of analyzed integration sites were within the
      chromosomal beta-globin LCR. None of the Ad.LCR-beta-GFP integrations occurred in
      exons. The integration pattern of a helper-dependent vector that contained X
      chromosomal stuffer DNA was different from that of the beta-globin LCR-containing
      vector. Infection of primary CD34(+) cells with Ad.LCR-beta-GFP did not affect
      the clonogenic capacity of CD34(+) cells. Transduction of CD34(+) cells with
      Ad.LCR-beta-GFP resulted in vector integration and erythroid lineage-specific GFP
      expression.

PMID- 16103152
TI  - Multiple gene segments control the temperature sensitivity and attenuation
      phenotypes of ca B/Ann Arbor/1/66.
AB  - Cold-adapted (ca) B/Ann Arbor/1/66 is the influenza B virus strain master donor
      virus for FluMist, a live, attenuated, influenza virus vaccine licensed in 2003
      in the United States. Each FluMist vaccine strain contains six gene segments of
      the master donor virus; these master donor gene segments control the vaccine's
      replication and attenuation. These gene segments also express characteristic
      biological traits in model systems. Unlike most virulent wild-type (wt) influenza
      B viruses, ca B/Ann Arbor/1/66 is temperature sensitive (ts) at 37 degrees C and
      attenuated (att) in the ferret model. In order to define the minimal genetic
      components of these phenotypes, the amino acid sequences of the internal genes of
      ca B/Ann Arbor/1/66 were aligned to those of other influenza B viruses. These
      analyses revealed eight unique amino acids in three proteins: two in the
      polymerase subunit PA, two in the M1 matrix protein, and four in the
      nucleoprotein (NP). Using reverse genetics, these eight wt amino acids were
      engineered into a plasmid-derived recombinant of ca B/Ann Arbor/1/66, and these
      changes reverted both the ts and the att phenotypes. A detailed mutational
      analysis revealed that a combination of two sites in NP (A114 and H410) and one
      in PA (M431) controlled expression of ts, whereas these same changes plus two
      additional residues in M1 (Q159 and V183) controlled the att phenotype.
      Transferring this genetic signature to the divergent wt B/Yamanashi/166/98 strain
      conferred both the ts and the att phenotypes on the recombinant, demonstrating
      that this small, complex, genetic signature encoded the essential elements for
      these traits.

PMID- 16103153
TI  - Characterization of an antisense transcript spanning the UL81-82 locus of human
      cytomegalovirus.
AB  - In this study we present the characterization of a novel transcript, UL81-82ast,
      UL81-82 antisense transcript, and its protein product. The transcript was
      initially found in a cDNA library of monocytes from a seropositive donor. mRNA
      was obtained from monocytes isolated from a healthy donor with a high antibody
      titer against human cytomegalovirus (HCMV). The mRNAs were cloned into a lambda
      phage-derived vector to create the cDNA library. Using PCR, UL81-82ast was
      amplified from the library. The library was tested for the presence of numerous
      HCMV genes. Neither structural genes nor immediate-early genes were found. UL81
      82ast was detected in five bone marrow samples from healthy antibody-positive
      donors. This same transcript was also found in in vitro-infected human
      fibroblasts early after infection but disappears at the same time that UL82
      transcription begins. Not only was the transcript amplified using reverse
      transcription-PCR and sequenced but its protein product (UL82as protein) was
      detected by both Western blot and immunofluorescence. Phylogenetic studies using
      UL82as protein were conducted, showing a high degree of conservation in clinical
      isolates, laboratory strains of HCMV, and even in chimpanzee CMV. The transcript
      could be involved in the posttranscriptional regulation of the UL82 gene,
      affecting its mRNA stability or translation. Since the UL82 product, pp71,
      functions as an immediate-early transactivator, its posttranscriptional control
      could have some effect over latency reactivation and lytic replication.

PMID- 16103154
TI  - The expression strategy of goose parvovirus exhibits features of both the
      Dependovirus and Parvovirus genera.
AB  - The RNA transcription profile of the goose parvovirus (GPV) was determined, and
      it is a surprising hybrid of features of the Parvovirus and Dependovirus genera
      of the Parvovirinae subfamily of the Parvoviridae. Similar to the Dependovirus
      adeno-associated virus type 5, RNAs transcribed from the GPV upstream P9
      promoter, which encode the viral nonstructural proteins, were polyadenylated at a
      high efficiency at a polyadenylation site [(pA)p] located within an intron in the
      center of the genome. Efficient usage of (pA)p required a downstream element that
      overlaps with the polypyrimidine tract of the A2 3' splice site of the central
      intron. An upstream element required for efficient use of (pA)p was also
      identified. RNAs transcribed from the P42 promoter, presumed to encode the viral
      capsid proteins, primarily extended through (pA)p and were polyadenylated at a
      site, (pA)d, located at the right end of the genome and ultimately spliced at a
      high efficiency. No promoter analogous to the Dependovirus P19 promoter was
      detected; however, similar to minute virus of mice and other members of the
      Parvovirus genus, a significant portion of pre-mRNAs generated from the P9
      promoter were additionally spliced within the putative GPV Rep1 coding region and
      likely encode an additional, smaller, nonstructural protein. Also similar to
      members of the Parvovirus genus, detectable activity of the GPV P42 promoter was
      highly dependent on transactivation by the GPV Rep1 protein in a manner dependent
      on binding to a cis-element located in the P42 promoter.

PMID- 16103155
TI  - Alpha/beta interferon differentially modulates the clearance of cytoplasmic
      encapsidated replication intermediates and nuclear covalently closed circular
      hepatitis B virus (HBV) DNA from the livers of hepatocyte nuclear factor 1alpha
      null HBV transgenic mice.
AB  - Treatment with alpha interferon is a standard therapy for patients with chronic
      hepatitis B virus (HBV) infections. This treatment can reduce virus load and
      ameliorate disease symptoms. However, in the majority of cases, alpha interferon
      therapy fails to resolve the chronic HBV infection. The reason alpha interferon
      therapy is inefficient at resolving chronic HBV infections is assumed to be
      because it fails to eliminate covalently closed circular (CCC) HBV DNA from the
      nuclei of infected hepatocytes. In an attempt to address this issue, the
      stability of HBV CCC DNA in response to alpha/beta interferon induction was
      examined in HNF1alpha-null HBV transgenic mice. Alpha/beta interferon induction
      by polyinosinic-polycytidylic acid [poly(I-C)] treatment efficiently eliminated
      encapsidated cytoplasmic HBV replication intermediates while only modestly
      reducing nuclear HBV CCC DNA. These observations indicate that nuclear HBV CCC
      DNA is more stable than cytoplasmic replication intermediates in response to
      alpha/beta interferon induction. Consequently it appears that for therapies to
      resolve chronic HBV infection efficiently, they will have to target the
      elimination of the most stable HBV replication intermediate, nuclear HBV CCC DNA.

PMID- 16103156
TI  - Dengue virus nonstructural protein NS5 induces interleukin-8 transcription and
      secretion.
AB  - Elevated circulating levels of chemokines have been reported in patients with
      dengue fever and are proposed to contribute to the pathogenesis of dengue
      disease. To establish in vitro models for chemokine induction by dengue 2 virus
      (DEN2V), we studied a variety of human cell lines and primary cells. DEN2V
      infection of HepG2 and primary dendritic cells induced the production of
      interleukin-8 (IL-8), RANTES, MIP-1alpha, and MIP-1beta, whereas only IL-8 and
      RANTES were induced following dengue virus infection of HEK293 cells. Chemokine
      secretion was accompanied by an increase in steady-state mRNA levels. No
      chemokine induction was observed in HEK293 cells treated with poly(I:C) or alpha
      interferon, suggesting a direct effect of virus infection. To determine the
      mechanism(s) involved in the induction of chemokine production by DEN2V,
      individual dengue virus genes were cloned into plasmids and expressed in HEK293
      cells. Transfection of a plasmid expressing NS5 or a dengue virus replicon
      induced IL-8 gene expression and secretion. RANTES expression was not induced
      under these conditions, however. Reporter assays showed that IL-8 induction by
      NS5 was principally through CAAT/enhancer binding protein, whereas DEN2V
      infection also induced NF-kappaB. These results indicate a role for the dengue
      virus NS5 protein in the induction of IL-8 by DEN2V infection. Recruitment and
      activation of potential target cells to sites of DEN2V replication by virus
      induced chemokine production may contribute to viral replication as well as to
      the inflammatory components of dengue virus disease.

PMID- 16103157
TI  - Dipyridamole reversibly inhibits mengovirus RNA replication.
AB  - Dipyridamole is an effective inhibitor of cardiovirus growth in cell culture. The
      effects of dipyridamole on mengovirus replication in vivo and in vitro were
      examined in the hope the drug could be used as an experimental analog of the
      poliovirus inhibitor guanidine. Guanidine selectively inhibits poliovirus RNA
      synthesis but not RNA translation, and as such, has been a valuable research
      tool. Although guanidine does not inhibit cardiovirus infection, a compound with
      similar discriminatory characteristics would be experimentally useful for
      parallel work with these viruses. We found that mengovirus plaque formation in
      HeLa or L cells was inhibited nearly 100% by the presence of 80 muM dipyridamole.
      The inhibitory effect was reversible and targeted an early step in the
      replication cycle. Studies with luciferase-expressing mengovirus replicons showed
      that viral protein synthesis was unaffected by dipyridamole, and rather, RNA
      synthesis was the step targeted by the drug. This assessment was confirmed by
      direct analyses of viral translation and RNA synthesis activities in a Krebs-2
      derived in vitro system that supported complete, infectious cardiovirus
      replication. In Krebs extracts, dipyridamole specifically inhibited viral RNA
      synthesis to more than 95%, with no concomitant effect on viral protein
      translation or polyprotein processing. The observed inhibition reversibly
      affected an early step in both minus-strand and plus-strand RNA synthesis,
      although inhibition of plus-strand synthesis was more profound than that of minus
      strand synthesis. We conclude that dipyridamole is a potent experimental tool
      that readily distinguishes between cardiovirus translation and RNA replication
      functions.

PMID- 16103158
TI  - RNA interference-mediated virus clearance from cells both acutely and chronically
      infected with the prototypic arenavirus lymphocytic choriomeningitis virus.
AB  - Several arenaviruses, including Lassa fever virus, cause severe, often lethal
      hemorrhagic fever in humans. No licensed vaccines are available in the United
      States, and currently there is no efficacious therapy to treat this viral
      infection. Therefore the importance of developing effective antiviral approaches
      to combat pathogenic arenaviruses is clear. Moreover, the prototypic arenavirus
      lymphocytic choriomeningitis virus (LCMV) is an important model for the study of
      viral persistence and associated diseases, as well as for exploring therapies to
      treat viral chronic infections. The use of small interfering RNAs (siRNAs) to
      downregulate gene expression via RNA interference (RNAi) has emerged as a
      powerful genetic tool for the study of gene function. In addition, the successful
      use of siRNAs to target a variety of animal viruses has led us to consider RNAi
      as a potential novel antiviral strategy. We have investigated the use of RNAi
      therapy against LCMV. Here, we show that siRNAs targeting sequences within the
      viral L polymerase and Z mRNAs inhibit LCMV multiplication in cultured cells.
      Unexpectedly, the antiviral efficacy of RNAi-based therapy against LCMV was
      highly dependent on the method used to deliver effector siRNA molecules. Thus,
      transfection of chemically synthesized siRNA pools to L and Z was ineffective in
      preventing virus multiplication. In contrast, targeting of the same viral L and Z
      gene products with siRNAs produced inside cells using a replication-deficient
      recombinant adenovirus expression system inhibited LCMV multiplication very
      efficiently. Notably, transduction with the replication-deficient recombinant
      adenovirus expression system to Z and L effectively cured persistently LCMV
      infected cells, suggesting the feasibility of using RNAi therapy to combat viral
      chronic infections by riboviruses.

PMID- 16103159
TI  - The cellular TATA binding protein is required for rep-dependent replication of a
      minimal adeno-associated virus type 2 p5 element.
AB  - The p5 promoter region of adeno-associated virus type 2 (AAV-2) is a
      multifunctional element involved in rep gene expression, Rep-dependent
      replication, and site-specific integration. We initially characterized a 350-bp
      p5 region by its ability to behave like a cis-acting replication element in the
      presence of Rep proteins and adenoviral factors. The objective of this study was
      to define the minimal elements within the p5 region required for Rep-dependent
      replication. Assays performed in transfected cells (in vivo) indicated that the
      minimal p5 element was composed by a 55-bp sequence (nucleotides 250 to 304 of
      wild-type AAV-2) containing the TATA box, the Rep binding site, the terminal
      resolution site present at the transcription initiation site (trs(+1)), and a
      downstream 17-bp region that could potentially form a hairpin structure
      localizing the trs(+1) at the top of the loop. Interestingly, the TATA box was
      absolutely required for in vivo but dispensable for in vitro, i.e., cell-free,
      replication. We also demonstrated that Rep binding and nicking at the trs(+1) was
      enhanced in the presence of the cellular TATA binding protein, and that
      overexpression of this cellular factor increased in vivo replication of the
      minimal p5 element. Together, these studies identified the minimal replication
      origin present within the AAV-2 p5 promoter region and demonstrated for the first
      time the involvement of the TATA box, in cis, and of the TATA binding protein, in
      trans, for Rep-dependent replication of this viral element.

PMID- 16103160
TI  - Monoclonal antibody AP33 defines a broadly neutralizing epitope on the hepatitis
      C virus E2 envelope glycoprotein.
AB  - Hepatitis C virus (HCV) remains a significant threat to the general health of the
      world's population, and there is a pressing need for the development of new
      treatments and preventative vaccines. Here, we describe the generation of
      retrovirus-based pseudoparticles (HCVpp) incorporating a panel of full-length
      E1E2 clones representative of the major genotypes 1 through 6, and their
      application to assess the reactivity and neutralizing capability of antisera and
      monoclonal antibodies raised against portions of the HCV E2 envelope protein.
      Rabbit antisera raised against either the first hypervariable region or
      ectodomain of E2 showed limited and strain specific neutralization. By contrast,
      the monoclonal antibody (MAb) AP33 demonstrated potent neutralization of
      infectivity against HCVpp carrying E1E2 representative of all genotypes tested.
      The concentration of AP33 required to achieve 50% inhibition of infection by
      HCVpp of diverse genotypes ranged from 0.6 to 32 mug/ml. The epitope recognized
      by MAb AP33 is linear and highly conserved across different genotypes of HCV.
      Thus, identification of a broadly neutralizing antibody that recognizes a linear
      epitope is likely to be of significant benefit to future vaccine and therapeutic
      antibody development.

PMID- 16103161
TI  - Down-regulation of p53 by double-stranded RNA modulates the antiviral response.
AB  - p53 has been well characterized as a tumor suppressor gene, but its role in
      antiviral defense remains unclear. A recent report has demonstrated that p53 can
      be induced by interferons and is activated after vesicular stomatitis virus (VSV)
      infection. We observed that different nononcogenic viruses, including
      encephalomyocarditis virus (EMCV) and human parainfluenza virus type 3 (HPIV3),
      induced down-regulation of p53 in infected cells. Double-stranded RNA (dsRNA) and
      a mutant vaccinia virus lacking the dsRNA binding protein E3L can also induce
      this effect, indicating that dsRNA formed during viral infection is likely the
      trigger for down-regulation of p53. The mechanism of down-regulation of p53 by
      dsRNA relies on translation inhibition mediated by the PKR and RNase L pathways.
      In the absence of p53, the replication of both EMCV and HPIV3 was retarded,
      whereas, conversely, VSV replication was enhanced. Cell cycle analysis indicated
      that wild-type (WT) but not p53 knockout (KO) fibroblasts undergo an early-G(1)
      arrest following dsRNA treatment. Moreover, in WT cells the onset of dsRNA
      induced apoptosis begins after p53 levels are down-regulated, whereas p53 KO
      cells, which lack the early-G(1) arrest, rapidly undergo apoptosis. Hence, our
      data suggest that the down-regulation of p53 facilitates apoptosis, thereby
      limiting viral replication.

PMID- 16103162
TI  - Impact of 2-bromo-5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole riboside and
      inhibitors of DNA, RNA, and protein synthesis on human cytomegalovirus genome
      maturation.
AB  - Herpesvirus genome maturation is a complex process in which concatemeric DNA
      molecules are translocated into capsids and cleaved at specific sequences to
      produce encapsidated-unit genomes. Bacteriophage studies further suggest that
      important ancillary processes, such as RNA transcription and DNA synthesis,
      concerned with repeat duplication, recombination, branch resolution, or damage
      repair may also be involved with the genome maturation process. To gain insight
      into the biochemical activities needed for herpesvirus genome maturation, 2-bromo
      5,6-dichloro-1-beta-d-ribofuranosyl benzimidazole riboside (BDCRB) was used to
      allow the accumulation of human cytomegalovirus concatemeric DNA while the
      formation of new genomes was being blocked. Genome formation was restored upon
      BDCRB removal, and addition of various inhibitors during this time window
      permitted evaluation of their effects on genome maturation. Inhibitors of protein
      synthesis, RNA transcription, and the viral DNA polymerase only modestly reduced
      genome formation, demonstrating that these activities are not required for genome
      maturation. In contrast, drugs that inhibit both viral and host DNA polymerases
      potently blocked genome formation. Radioisotope incorporation in the presence of
      a viral DNA polymerase inhibitor further suggested that significant host-mediated
      DNA synthesis occurs throughout the viral genome. These results indicate a role
      for host DNA polymerases in genome maturation and are consistent with a need for
      terminal repeat duplication, debranching, or damage repair concomitant with DNA
      packaging or cleavage. Similarities to previously reported effects of BDCRB on
      guinea pig cytomegalovirus were also noted; however, BDCRB induced low-level
      formation of a supergenomic species called monomer+ DNA that is unique to human
      cytomegalovirus. Analysis of monomer+ DNA suggested a model for its formation in
      which BDCRB permits limited packaging of concatemeric DNA but induces skipping of
      cleavage sites.

PMID- 16103163
TI  - Epstein-Barr virus can establish infection in the absence of a classical memory B
      cell population.
AB  - Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that persists in the
      body for life after primary infection. The primary site of EBV persistence is the
      memory B lymphocyte, but whether the virus initially infects naive or memory B
      cells is still disputed. We have analyzed EBV infection in nine cases of X-linked
      hyper-immunoglobulin M (hyper-IgM) syndrome who, due to a mutation in CD40 ligand
      gene, do not have a classical, class-switched memory B-cell population (IgD(-)
      CD27(+)). We found evidence of EBV infection in 67% of cases, which is similar to
      the infection rate found in the general United Kingdom population (60 to 70% for
      the relevant age range). We detected EBV DNA in peripheral blood B cells and
      showed in one case that the infection was restricted to the small population of
      nonclassical, germinal center-independent memory B cells (IgD(+) CD27(+)).
      Detection of EBV small RNAs, latent membrane protein 2, and EBV nuclear antigen
      3C expression in peripheral blood suggests full latent viral gene expression in
      this population. Analysis of EBV DNA in serial samples showed variability over
      time, suggesting cycles of infection and loss. Our results demonstrate that short
      term EBV persistence can occur in the absence of a germinal center reaction and a
      classical memory B-cell population.

PMID- 16103164
TI  - Ubiquitylation of Cdk9 by Skp2 facilitates optimal Tat transactivation.
AB  - By recruiting the positive transcriptional elongation factor b (P-TEFb) to paused
      RNA polymerase II, the transactivator Tat stimulates transcriptional elongation
      of the human immunodeficiency virus type 1 (HIV-1) genome. We found that cyclin
      dependent kinase 9 (Cdk9), the catalytic subunit of P-TEFb, is ubiquitylated in
      vivo. This ubiquitylation depended on the Skp1/Cul1/F-box protein E3 ubiquitin
      ligase Skp2. Likewise, Tat required Skp2 since its transactivation of the HIV-1
      long terminal repeat decreased in primary mouse embryonic fibroblasts, which
      lacked Skp2. The ubiquitylation of Cdk9 by Skp2 facilitated the formation of the
      ternary complex between P-TEFb, Tat, and transactivation response element. Thus,
      our findings underscore the requirement of ubiquitylation for the coactivator
      function in regulating HIV-1 transcriptional elongation.

PMID- 16103165
TI  - Genetic and molecular in vivo analysis of herpes simplex virus assembly in murine
      visual system neurons.
AB  - Herpes simplex virus (HSV) infects both epithelial cells and neuronal cells of
      the human host. Although HSV assembly has been studied extensively for cultured
      epithelial and neuronal cells, cultured neurons are biochemically,
      physiologically, and anatomically significantly different than mature neurons in
      vivo. Therefore, it is imperative that viral maturation and assembly be studied
      in vivo. To study viral assembly in vivo, we inoculated wild-type and replication
      defective viruses into the posterior chamber of mouse eyes and followed infection
      in retinal ganglion cell bodies and axons. We used PCR techniques to detect viral
      DNA and RNA and electron microscopy immunohistochemistry and Western blotting to
      detect viral proteins in specific portions of the optic tract. This approach has
      shown that viral DNA replication is necessary for viral DNA movement into axons.
      Movement of viral DNA along ganglion cell axons occurs within capsid-like
      structures at the speed of fast axonal transport. These studies show that the
      combined use of intravitreal injections of replication-defective viruses and
      molecular probes allows the genetic analysis of essential viral replication and
      maturation processes in neurons in vivo. The studies also provide novel direct
      evidence for the axonal transport of viral DNA and support for the subassembly
      hypothesis of viral maturation in situ.

PMID- 16103166
TI  - Differential pathogenesis of primary CCR5-using human immunodeficiency virus type
      1 isolates in ex vivo human lymphoid tissue.
AB  - In the course of human immunodeficiency virus (HIV) disease, CCR5-utilizing HIV
      type 1 (HIV-1) variants (R5), which typically transmit infection and dominate its
      early stages, persist in approximately half of the infected individuals
      (nonswitch virus patients), while in the other half (switch virus patients),
      viruses using CXCR4 (X4 or R5X4) emerge, leading to rapid disease progression.
      Here, we used a system of ex vivo tonsillar tissue to compare the pathogeneses of
      sequential primary R5 HIV-1 isolates from patients in these two categories. The
      absolute replicative capacities of HIV-1 isolates seemed to be controlled by
      tissue factors. In contrast, the replication level hierarchy among sequential
      isolates and the levels of CCR5(+) CD4(+) T-cell depletion caused by the R5
      isolates seemed to be controlled by viral factors. R5 viruses isolated from
      nonswitch virus patients depleted more target cells than R5 viruses isolated from
      switch virus patients. The high depletion of CCR5(+) cells by HIV-1 isolates from
      nonswitch virus patients may explain the steady decline of CD4(+) T cells in
      patients with continuous dominance of R5 HIV-1. The level of R5 pathogenicity, as
      measured in ex vivo lymphoid tissue, may have a predictive value reflecting
      whether, in an infected individual, X4 HIV-1 will eventually dominate.

PMID- 16103167
TI  - Ternary complex formation of human immunodeficiency virus type 1 Env, CD4, and
      chemokine receptor captured as an intermediate of membrane fusion.
AB  - Human immunodeficiency virus (HIV) Env-induced fusion is highly temperature
      dependent. When effector and target cells were coincubated at 37 degrees C, there
      was a kinetic delay before fusion commenced. When effector and target cells were
      coincubated for varied times at 23 degrees C, a temperature that does not permit
      fusion, a temperature-arrested stage was created. Raising temperature to 37
      degrees C from the 23 degrees C intermediate eliminated the kinetic delay.
      Inhibitors (T22, AMD3100, and Sch-C) that block fusion by binding chemokine
      receptors were added after creating the intermediate so as to assess the extent
      of engagement between gp120 and chemokine receptors at that stage. For both CXCR4
      and CCR5 as coreceptors, increasingly long times of coincubation at 23 degrees C
      reduced the efficacy of the coreceptor-binding inhibitors in blocking fusion.
      This implies that an increasing number of ternary Env/CD4/coreceptor complexes
      form over time at 23 degrees C. It also shows that ternary complex formation has
      a lower temperature threshold than the downstream steps that include Env folding
      into a six-helix bundle; this provides an experimental means to separate
      coreceptor binding by gp120 from the subsequent refolding of gp41 into a six
      helix bundle structure. As the time of cell coincubation at 23 degrees C was
      prolonged, more cells quickly fused upon the raising of the temperature to 37
      degrees C, and the increase quantitatively correlated with the greater percentage
      of fusion that was resistant to drugs. Therefore the pronounced kinetic delay in
      HIV Env-induced fusion is caused predominantly by the time needed for ternary
      complexes to form.

PMID- 16103168
TI  - Cross-reactivity of T lymphocytes recognizing a human cytotoxic T-lymphocyte
      epitope within BK and JC virus VP1 polypeptides.
AB  - A transgenic mouse model was used to identify an HLA-A*02-restricted epitope
      within the VP1 polypeptide of a human polyomavirus, BK virus (BKV), which is
      associated with polyomavirus-associated nephropathy in kidney transplant
      patients. Peptide stimulation of splenocytes from mice immunized with recombinant
      modified vaccinia virus Ankara expressing BKV VP1 resulted in expansion of
      cytotoxic T lymphocytes (CTLs) recognizing the sequence LLMWEAVTV corresponding
      to amino acid residues 108 to 116 (BKV VP1p108). These effector T-cell
      populations represented functional CTLs as assessed by cytotoxicity and cytokine
      production and were cross-reactive against antigen-presenting cells pulsed with a
      peptide corresponding to the previously described JC virus (JCV) VP1 homolog
      sequence ILMWEAVTL (JCV VP1p100) (I. J. Koralnik et al., J. Immunol. 168:499-504,
      2002). A panel of 10 healthy HLA-A*02 human volunteers and two kidney transplant
      recipients were screened for T-cell immunity to this BK virus VP1 epitope by in
      vitro stimulation of their peripheral blood mononuclear cells (PBMC) with the BKV
      VP1p108 peptide, followed by tetramer labeling combined with simultaneous assays
      to detect intracellular cytokine production and degranulation. PBMC from 4/10
      subjects harbored CTL populations that recognized both the BKV VP1p108 and the
      JCV VP1p100 peptides with comparable efficiencies as measured by tetramer
      binding, gamma interferon production, and degranulation. CTL responses to the JCV
      VP1p100 epitope have been associated with prolonged survival in progressive
      multifocal leukoencephalopathy patients (R. A. Du Pasquier et al., Brain 127:1970
      1978, 2004; I. J. Koralnik et al., J. Immunol. 168:499-504, 2002). Given that
      both human polyomaviruses are resident in a high proportion of healthy
      individuals and that coinfection occurs (W. A. Knowles et al., J. Med. Virol.
      71:115-123, 2003), our findings suggest a reinterpretation of this protective T
      cell immunity, suggesting that the same VP1 epitope is recognized in HLA-A*02
      persons in response to either BK or JC virus infection.

PMID- 16103169
TI  - The nonnucleoside reverse transcriptase inhibitor UC-781 inhibits human
      immunodeficiency virus type 1 infection of human cervical tissue and
      dissemination by migratory cells.
AB  - Heterosexual transmission of human immunodeficiency virus remains the major route
      of transmission worldwide; thus, there is an urgent need for additional
      prevention strategies, particularly those that could be controlled by women.
      Using cellular and tissue explant models, we have evaluated the potential
      activity of thiocarboxanilide nonnucleoside analogue reverse transcriptase
      inhibitor UC-781 as a vaginal microbicide. We were able to demonstrate a potent
      dose-dependent effect against R5 and X4 infections of T cells. In human cervical
      explant cultures, UC-781 was not only able to inhibit direct infection of mucosal
      tissue but was able to prevent dissemination of virus by migratory cells. UC-781
      formulated into a carbopol gel (0.1%) retained significant activity against both
      direct tissue infection and transinfection mediated by migratory cells.
      Furthermore, UC-781 demonstrated prolonged inhibitory effects able to prevent
      both localized and disseminated infections up to 6 days post compound treatment.
      Additional studies were carried out to determine the concentration of compound
      that might be required to block a primary infection within draining lymph nodes.
      While a greater dose of compound was required to inhibit both X4 and R5
      infections of lymphoid versus cervical explants, this was equivalent to a 1:3,000
      dilution of the 0.1% formulation. Furthermore, a 2-h exposure to the compound
      prevented infection of lymphoid tissue when challenged up to 2 days later. The
      prolonged protection observed following pretreatment of both genital and lymphoid
      tissues with UC-781 suggests that this class of inhibitors may have unique
      advantages over other classes of potential microbicide candidates.

PMID- 16103170
TI  - Effects of conserved RNA secondary structures on hepatitis delta virus genotype I
      RNA editing, replication, and virus production.
AB  - RNA editing of the hepatitis delta virus (HDV) antigenome at the amber/W site by
      the host RNA adenosine deaminase ADAR1 is a critical step in the HDV replication
      cycle. Editing is required for production of the viral protein hepatitis delta
      antigen long form (HDAg-L), which is necessary for viral particle production but
      can inhibit HDV RNA replication. The RNA secondary structural features in ADAR1
      substrates are not completely defined, but base pairing in the 20-nucleotide (nt)
      region 3' of editing sites is thought to be important. The 25-nt region 3' of the
      HDV amber/W site in HDV genotype I RNA consists of a conserved secondary
      structure that is mostly base paired but also has asymmetric internal loops and
      single-base bulges. To understand the effect of this 3' region on the HDV
      replication cycle, mutations that either increase or decrease base pairing in
      this region were created and the effects of these changes on amber/W site
      editing, RNA replication, and virus production were studied. Increased base
      pairing, particularly in the region 15 to 25 nt 3' of the editing site,
      significantly increased editing; disruption of base pairing in this region had
      little effect. Increased editing resulted in a dramatic inhibition of HDV RNA
      synthesis, mostly due to excess HDAg-L production. Although virus production at
      early times was unaffected by this reduced RNA replication, at later times it was
      significantly reduced. Therefore, it appears that the conserved RNA secondary
      structure around the HDV genotype I amber/W site has been selected not for the
      highest editing efficiency but for optimal viral replication and secretion.

PMID- 16103171
TI  - Endothelial cells promote human immunodeficiency virus replication in nondividing
      memory T cells via Nef-, Vpr-, and T-cell receptor-dependent activation of NFAT.
AB  - Human endothelial cells (ECs) enhance human immunodeficiency virus (HIV)
      replication within CD4(+) memory T cells by 50,000-fold in a Nef-dependent
      manner. Here, we report that EC-mediated HIV type 1 replication is also dependent
      on an intact vpr gene. Moreover, we demonstrate that despite a requirement for
      engaging major histocompatibility complex (MHC) class II molecules and
      costimulators, EC-stimulated virus-producing cells (p24(high) T cells) do not
      proliferate, nor are they arrested in the cell cycle. Rather, they are minimally
      activated, sometimes expressing CD69 but not CD25, HLA-DR, VLA-1, or effector
      cytokines. Blocking antibodies to interleukin 2 (IL-2), IL-6, IL-7, or tumor
      necrosis factor do not inhibit viral replication. Cyclosporine effectively
      inhibits viral replication, as does disruption of the NFAT binding site in the
      viral long terminal repeat. Furthermore, in the presence of ECs, suboptimal T
      cell receptor (TCR) stimulation with phytohemagglutinin L supports efficient
      viral replication, and suboptimal stimulation with toxic shock syndrome toxin 1
      leads to viral replication selectively in the TCR-stimulated, Vbeta2-expressing T
      cells. Collectively, these data indicate that ECs provide signals that promote
      Nef- and Vpr-dependent HIV replication in memory T cells that have been minimally
      activated through their TCRs. Our studies suggest a mechanism for HIV replication
      in vivo within the reservoir of circulating memory CD4(+) T cells that persist
      despite antiretroviral therapy and further suggest that maintenance of
      immunological memory by MHC class II-expressing ECs via TCR signaling may
      contribute to HIV rebound following cessation of antiretroviral therapy.

PMID- 16103172
TI  - Glycosylation, disulfide bond formation, and the presence of a WSXWS-like motif
      in the orf virus GIF protein are critical for maintaining the integrity of
      Binding to ovine granulocyte-macrophage colony-stimulating factor and interleukin
      2.
AB  - Orf virus (ORFV), the type species of the family Parapoxviridae, encodes a
      protein (GIF) that binds and inhibits the ovine cytokines granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2). There is no obvious
      sequence homology between the ORFV protein and any known mammalian GM-CSF- or IL
      2-binding proteins. We demonstrate here that many of the biochemical properties
      of mammalian GM-CSF receptors that are required for efficient binding of GM-CSF
      are also critical to the GIF protein for binding to ovine GM-CSF (ovGM-CSF). Site
      directed mutagenesis of the GIF protein demonstrated, first, the importance of
      disulfide bonds, and second, that a sequence motif (WDPWV), related to the WSXWS
      motif of the type 1 cytokine receptor superfamily, was necessary for biological
      activity. Finally, glycosylation of the GIF protein was also critical for binding
      to GM-CSF.

PMID- 16103173
TI  - Human immunodeficiency virus type 1 subtype B ancestral envelope protein is
      functional and elicits neutralizing antibodies in rabbits similar to those
      elicited by a circulating subtype B envelope.
AB  - Human immunodeficiency virus type 1 (HIV-1) is a difficult target for vaccine
      development, in part because of its ever-expanding genetic diversity and
      attendant capacity to escape immunologic recognition. Vaccine efficacy might be
      improved by maximizing immunogen antigenic similarity to viruses likely to be
      encountered by vaccinees. To this end, we designed a prototype HIV-1 envelope
      vaccine using a deduced ancestral state for the env gene. The ancestral state
      reconstruction method was shown to be >95% accurate by computer simulation and
      99.8% accurate when estimating the known inoculum used in an experimental
      infection study in rhesus macaques. Furthermore, the deduced ancestor gene
      differed from the set of sequences used to derive the ancestor by an average of
      12.3%, while these latter sequences were an average of 17.3% different from each
      other. A full-length ancestral subtype B HIV-1 env gene was constructed and shown
      to produce a glycoprotein of 160 kDa that bound and fused with cells expressing
      the HIV-1 coreceptor CCR5. This Env was also functional in a virus pseudotype
      assay. When either gp160- or gp140-expressing plasmids and recombinant gp120 were
      used to immunize rabbits in a DNA prime-protein boost regimen, the artificial
      gene induced immunoglobulin G antibodies capable of weakly neutralizing
      heterologous primary HIV-1 strains. The results were similar for rabbits
      immunized in parallel with a natural isolate, HIV-1 SF162. Further design efforts
      to better present conserved neutralization determinants are warranted.

PMID- 16103174
TI  - Role of plasminogen in propagation of scrapie.
AB  - To investigate whether plasminogen may feature in scrapie infection, we
      inoculated plasminogen-deficient (Plg(-/-)), heterozygous plasminogen-deficient
      (Plg(+/-)), and wild-type (Plg(+/+)) mice by the intracerebral or intraperitoneal
      (i.p.) route with the RML scrapie strain and monitored the onset of neurological
      signs of disease, survival time, brain, and accumulation of scrapie disease
      associated forms of the prion protein (PrP(Sc)). Only after i.p. inoculation, a
      slight, although significant, difference in survival (P < 0.05) between Plg(-/-)
      and Plg(+/+) mice was observed. Neuropathological examination and Western blot
      analysis were carried out when the first signs of disease appeared in Plg(+/+)
      animals (175 days after i.p. inoculation) and when mice reached the terminal
      stage of illness. At the onset of symptoms, PrP(Sc) accumulation was higher in
      the brain and spleen of Plg(+/+) and Plg(+/-) mice than in those of Plg(-/-)
      mice, and these differences were paralleled by differences in the severity of
      spongiform changes and astrogliosis in the cerebral cortex and subcortical gray
      structures. Immunohistochemical analysis of the spleens before inoculation did
      not show any impairment of the immune system affecting follicular dendritic or
      lymphoid cells in Plg(-/-) mice. Once the disease progressed and mice began to
      die of infection, differences were no longer apparent in either brains or
      spleens. In conclusion, our data indicate that plasminogen has no major effect on
      the survival of scrapie agent-infected mice.

PMID- 16103175
TI  - Antigenic stimulation specifically reactivates the replication of archived simian
      immunodeficiency virus genomes in chronically infected macaques.
AB  - Human immunodeficiency virus/simian immunodeficiency virus (SIV) diversification
      is a direct consequence of viral replication and occurs principally in secondary
      lymphoid organs where CD4(+) T cells are activated and proliferate. However, the
      evolution of viral quasispecies may also be driven by various nonexclusive
      mechanisms, including adaptation to specific immune responses and modification of
      viral fitness. Analysis of viral quasispecies in SIV-infected macaques subjected
      to repeated antigenic stimulations allowed us to demonstrate transient expansions
      of SIV populations that were highly dependent upon activation of antigen-specific
      T cells. T-cell clones expanded in response to a particular antigen were infected
      by a specific viral population and persisted for prolonged periods. Upon a second
      stimulation by encounter with the same antigen, these specific genomes were at
      the origin of a new burst of replication, leading to rapid but transient
      replacement of the viral quasispecies in blood. Finally, longitudinal analysis of
      SIV sequence variation during and between antigenic stimulations revealed that
      viral evolution is mostly constrained to periods of strong immunological
      activity.

PMID- 16103176
TI  - Functional constraints of influenza A virus epitopes limit escape from cytotoxic
      T lymphocytes.
AB  - Viruses can exploit a variety of strategies to evade immune surveillance by
      cytotoxic T lymphocytes (CTL), including the acquisition of mutations in CTL
      epitopes. Also for influenza A viruses a number of amino acid substitutions in
      the nucleoprotein (NP) have been associated with escape from CTL. However, other
      previously identified influenza A virus CTL epitopes are highly conserved,
      including the immunodominant HLA-A*0201-restricted epitope from the matrix
      protein, M1(58-66). We hypothesized that functional constraints were responsible
      for the conserved nature of influenza A virus CTL epitopes, limiting escape from
      CTL. To assess the impact of amino acid substitutions in conserved epitopes on
      viral fitness and recognition by specific CTL, we performed a mutational analysis
      of CTL epitopes. Both alanine replacements and more conservative substitutions
      were introduced at various positions of different influenza A virus CTL epitopes.
      Alanine replacements for each of the nine amino acids of the M1(58-66) epitope
      were tolerated to various extents, except for the anchor residue at the second
      position. Substitution of anchor residues in other influenza A virus CTL epitopes
      also affected viral fitness. Viable mutant viruses were used in CTL recognition
      experiments. The results are discussed in the light of the possibility of
      influenza viruses to escape from specific CTL. It was speculated that functional
      constraints limit variation in certain epitopes, especially at anchor residues,
      explaining the conserved nature of these epitopes.

PMID- 16103177
TI  - Broad cross-clade T-cell responses to gag in individuals infected with human
      immunodeficiency virus type 1 non-B clades (A to G): importance of HLA anchor
      residue conservation.
AB  - We aimed to identify cross-clade human immunodeficiency virus type 1 (HIV-1)
      specific T-cell responses among 10 HLA-typed individuals who were infected with
      non-B HIV-1 strains (A, AG, C, D, G, or F) and to correlate these responses with
      genetic variation in documented T-cell epitopes. T-cell reactivity was tested
      against peptide pools spanning clade B Gag, Pol, Nef, Rev, and Tat consensus,
      with Gag and Nef providing the highest responses. Nine individuals who responded
      to clade B Gag demonstrated cross-reactive T-cell responses against clade A and C
      Gag pools, while six of seven responders to Nef-B reacted to clade A and C Nef
      pools. An inverse correlation between the height of the T-cell responses and the
      sequence divergence of the HLA class I-restricted epitopes was identified when we
      compared autologous Gag and Nef sequences with the reactive consensus pools. This
      could be explained for the Gag sequences through observed variations in the HLA
      anchor residues. Through mapping of 30 amino acid cross-clade-reactive regions
      using Gag-B pools, we were able to link 58% (14/24) of the T-cell responses to
      regions containing previously described HLA class I-restricted epitopes. Forty
      two percent (10/24) of the responses were directed to regions containing new
      epitopes, for which predicted HLA class I motifs could be recognized in 70%
      (7/10) of individuals. We demonstrate here that cross-clade T-cell responses are
      frequently induced in individuals infected with distinct HIV-1 clades, suggesting
      that interclade variation outside of HLA anchor residues may have less impact on
      vaccine-induced T-cell reactivity than previously thought.

PMID- 16103178
TI  - CD46-utilizing adenoviruses inhibit C/EBPbeta-dependent expression of
      proinflammatory cytokines.
AB  - The majority of adenovirus serotypes utilize the coxsackievirus-adenovirus
      receptor (CAR) for virus-host cell attachment, but subgroup B and subgroup D
      (adenovirus type 37 [Ad37]) viruses recognize CD46. CD46 is a ubiquitously
      expressed receptor that serves as a cofactor for the inactivation of the
      complement components C3b and C4b, and it also serves as a receptor for diverse
      microbial pathogens. A reported consequence of CD46 engagement is a reduced
      capability of human immune cells to express interleukin-12 (IL-12), a cytokine
      involved in both the innate and adaptive immune responses. Studies were thus
      undertaken to determine whether CD46-utilizing Ads alter the expression of
      proinflammatory cytokines. Subgroup B (Ad16 and -35) and Ad37, but not Ad2 or -5,
      significantly reduced IL-12 production by human peripheral blood mononuclear
      cells stimulated with gamma interferon (IFN-gamma) and lipopolysaccharide. IL-12
      mRNA (p35 and p40 subunits) levels as well as other cytokine mRNA levels (IL
      1alpha and -beta, IL-1Ra, and IL-6) were decreased upon interaction with CD46
      utilizing Ads. Analysis of transcription factor activity required for cytokine
      expression indicated that CD46-utilizing Ads preferentially inhibited IFN-gamma
      induced C/EBPbeta protein expression, consequently reducing its ability to form
      DNA complexes. Interference with IFN-gamma signaling events by CD46-utilizing
      Ads, but not CAR-utilizing Ads, reveals a potentially critical difference in the
      host immune response against distinct Ad vectors, a situation that has
      implications for gene delivery and vaccine development.

PMID- 16103179
TI  - Are ducks contributing to the endemicity of highly pathogenic H5N1 influenza
      virus in Asia?
AB  - Wild waterfowl are the natural reservoir of all influenza A viruses, and these
      viruses are usually nonpathogenic in these birds. However, since late 2002, H5N1
      outbreaks in Asia have resulted in mortality among waterfowl in recreational
      parks, domestic flocks, and wild migratory birds. The evolutionary stasis between
      influenza virus and its natural host may have been disrupted, prompting us to ask
      whether waterfowl are resistant to H5N1 influenza virus disease and whether they
      can still act as a reservoir for these viruses. To better understand the biology
      of H5N1 viruses in ducks and attempt to answer this question, we inoculated
      juvenile mallards with 23 different H5N1 influenza viruses isolated in Asia
      between 2003 and 2004. All virus isolates replicated efficiently in inoculated
      ducks, and 22 were transmitted to susceptible contacts. Viruses replicated to
      higher levels in the trachea than in the cloaca of both inoculated and contact
      birds, suggesting that the digestive tract is not the main site of H5N1 influenza
      virus replication in ducks and that the fecal-oral route may no longer be the
      main transmission path. The virus isolates' pathogenicities varied from
      completely nonpathogenic to highly lethal and were positively correlated with
      tracheal virus titers. Nevertheless, the eight virus isolates that were
      nonpathogenic in ducks replicated and transmitted efficiently to naive contacts,
      suggesting that highly pathogenic H5N1 viruses causing minimal signs of disease
      in ducks can propagate silently and efficiently among domestic and wild ducks in
      Asia and that they represent a serious threat to human and veterinary public
      health.

PMID- 16103180
TI  - Virulent variants emerging in mice infected with the apathogenic prototype strain
      of the parvovirus minute virus of mice exhibit a capsid with low avidity for a
      primary receptor.
AB  - The mechanisms involved in the emergence of virulent mammalian viruses were
      investigated in the adult immunodeficient SCID mouse infected by the attenuated
      prototype strain of the parvovirus Minute Virus of Mice (MVMp). Cloned MVMp
      intravenously inoculated in mice consistently evolved during weeks of subclinical
      infection to variants showing altered plaque phenotypes. All the isolated large
      plaque variants spread systemically from the oronasal cavity and replicated in
      major organs (brain, kidney, liver), in sharp contrast to the absolute inability
      of the MVMp and small-plaque variants to productively invade SCID organs by this
      natural route of infection. The virulent variants retained the MVMp capacity to
      infect mouse fibroblasts, consistent with the lack of genetic changes across the
      220-to-335 amino acid sequence of VP2, a capsid domain containing main
      determinants of MVM tropism. However, the capsid of the virulent variants shared
      a lower affinity than the wild type for a primary receptor used in the cytotoxic
      infection. The capsid gene of a virulent variant engineered in the MVMp
      background endowed the recombinant virus with a large-plaque phenotype, lower
      affinity for the receptor, and productive invasiveness by the oronasal route in
      SCID mice, eventually leading to 100% mortality. In the analysis of virulence in
      mice, both MVMp and the recombinant virus similarly gained the bloodstream 1 to 2
      days postoronasal inoculation and remained infectious when adsorbed to blood
      cells in vitro. However, the wild-type MVMp was cleared from circulation a few
      days afterwards, in contrast to the viremia of the recombinant virus, which was
      sustained for life. Significantly, attachment to an abundant receptor of primary
      mouse kidney epithelial cells by both viruses could be quantitatively competed by
      wild-type MVMp capsids, indicating that virulence is not due to an extended
      receptor usage in target tissues. We conclude that the selection of capsid
      receptor interactions of low affinity, which favors systemic infection, is a
      major evolutionary process in the adaptation of parvoviruses to new hosts and in
      the cause of disease.

PMID- 16103181
TI  - The UL7 gene of pseudorabies virus encodes a nonessential structural protein
      which is involved in virion formation and egress.
AB  - Homologues of the UL7 gene of herpes simplex virus type 1 are conserved in alpha
      , beta-, and gammaherpesviruses. However, little is known about their functions.
      Using a monospecific rabbit antiserum raised against a bacterial fusion protein,
      we identified the UL7 gene product of the neurotropic alphaherpesvirus
      pseudorabies virus (PrV). In Western blot analyses of infected cells and purified
      PrV particles the serum specifically detected a 29-kDa protein, which matches the
      calculated mass of the 266-amino-acid translation product of PrV UL7. For
      functional analysis, UL7 was deleted by mutagenesis of an infectious full-length
      clone of the PrV genome in Escherichia coli. The obtained recombinant PrV
      DeltaUL7F was replication competent in rabbit kidney cells, but maximum virus
      titers were decreased nearly 10-fold and plaque diameters were reduced by ca. 60%
      compared to wild-type PrV. Electron microscopy of infected cells revealed that in
      the absence of UL7, formation and nuclear egress of nucleocapsids were not
      affected, whereas secondary envelopment of cytoplasmic nucleocapsids appeared to
      be delayed and release of mature virions was less efficient. The observed
      replication defects were corrected by repair of the viral UL7 gene or by
      propagation of PrV-DeltaUL7F in UL7-expressing cells. PrV-DeltaUL7F was
      moderately attenuated in mice. Compared to wild-type virus, mean survival times
      were prolonged from 2 to 3 days after intranasal infection. However,
      neuroinvasion and transneuronal spread of PrV were not abolished in the absence
      of UL7. Thus, UL7 encodes a virion protein of PrV, which plays a role during
      virion maturation and egress both in vitro and in vivo.

PMID- 16103182
TI  - Variation in interferon sensitivity and induction among strains of eastern equine
      encephalitis virus.
AB  - Eastern equine encephalitis virus (EEEV) causes human encephalitis in North
      America (NA), but in South America (SA) it has rarely been associated with human
      disease, suggesting that SA strains are less virulent. To evaluate the hypothesis
      that this virulence difference is due to a greater ability of NA strains to evade
      innate immunity, we compared replication of NA and SA strains in Vero cells
      pretreated with interferon (IFN). Human IFN-alpha, -beta, and -gamma generally
      exhibited less effect on replication of NA than SA strains, supporting this
      hypothesis. In the murine model, no consistent difference in IFN induction was
      observed between NA and SA strains. After infection with most EEEV strains,
      higher viremia levels and shorter survival times were observed in mice deficient
      in IFN-alpha/beta receptors than in wild-type mice, suggesting that IFN
      alpha/beta is important in controlling replication. In contrast, IFN-gamma
      receptor-deficient mice infected with NA and SA strains had similar viremia
      levels and mortality rates to those of wild-type mice, suggesting that IFN-gamma
      does not play a major role in murine protection. Mice pretreated with poly(I-C),
      a nonspecific IFN inducer, exhibited dose-dependent protection against fatal
      eastern equine encephalitis, further evidence that IFN is important in
      controlling disease. Overall, our in vivo results did not support the hypothesis
      that NA strains are more virulent in humans due to their greater ability to
      counteract the IFN response. However, further studies using a better model of
      human disease are needed to confirm the results of differential human IFN
      sensitivity obtained in our in vitro experiments.

PMID- 16103183
TI  - Evidence that the respiratory syncytial virus polymerase is recruited to
      nucleotides 1 to 11 at the 3' end of the nucleocapsid and can scan to access
      internal signals.
AB  - The 3'-terminal end of the respiratory syncytial virus genomic RNA contains a 44
      nucleotide leader (Le) region adjoining the gene start signal of the first gene.
      Previous mapping studies demonstrated that there is a promoter located at the 3'
      end of Le, which can signal initiation of antigenome synthesis. The aim of this
      study was to investigate the role of the 3' terminus of the RNA template in (i)
      promoter recognition and (ii) determining the initiation site for antigenome
      synthesis. A panel of minigenomes containing additional sequence at the 3' end of
      the Le were analyzed for their ability to direct antigenome and mRNA synthesis.
      Minigenomes containing heterologous extensions of 6 nucleotides or more were
      unable to support efficient RNA synthesis. However, the activity of a minigenome
      with a 56-nucleotide extension could be restored by insertion of Le nucleotides 1
      to 11 or 1 to 13 at the 3' end, indicating that these nucleotides, in conjunction
      with the 3' terminus, are sufficient to recruit polymerase to the template.
      Northern blot and 5' rapid amplification of cDNA ends analysis of antigenome RNA
      indicated that antigenome initiation occurred at the first position of Le,
      irrespective of the terminal extension. This finding demonstrates that the 3'
      terminus of the RNA is not necessary for determining the antigenome initiation
      site. Data are presented which suggest that following recruitment to a promoter
      at the 3' end of Le, the polymerase is able to scan and respond to a promoter
      signal embedded within the RNA template.

PMID- 16103184
TI  - Herpes simplex virus type 1 infection leads to loss of serine-2 phosphorylation
      on the carboxyl-terminal domain of RNA polymerase II.
AB  - Previous studies have shown that herpes simplex virus type 1 (HSV-1) infection
      alters the phosphorylation of the carboxyl-terminal domain (CTD) of RNA
      polymerase II (RNAP II), creating a new form of the enzyme known as RNAP II(I).
      However, the specific phosphorylation changes induced by HSV-1 have not been
      characterized. In this study, we used phospho-specific anti-CTD antibodies to
      probe the structure of the postinfection RNAP II. We find that RNAP II(I) is
      phosphorylated on serine-5 (Ser-5) of the CTD consensus repeat but generally
      lacks phosphorylation on serine-2 (Ser-2). Since Ser-2 phosphorylation is
      normally associated with efficient transcriptional elongation and the recruitment
      of pre-mRNA processing factors, our results suggest that RNAP II(I) may have
      altered elongation properties and decreased interactions with the mRNA processing
      machinery. The viral factors responsible for the reduction in Ser-2 CTD
      phosphorylation were studied. We found that viral immediate-early (IE) gene
      expression is required and sufficient, in the context of infection, for loss of
      Ser-2 phosphorylation. However, studies with viral mutants failed to implicate a
      single IE protein (among ICP0, ICP4, ICP22, and ICP27) in this process. Although
      most Ser-2-phosphorylated RNAP II is lost after infection, our immunofluorescence
      analyses identified a small subfraction that escapes loss and relocalizes to
      splicing antigen-rich nuclear speckles. A similar phenomenon is seen in
      uninfected cells after various treatments that inhibit RNAP II transcription. We
      hypothesize that the HSV-1-induced relocalization of residual Ser-2
      phosphorylated RNAP II to nuclear speckles reflects a host response to the
      inhibition of cellular gene transcription.

PMID- 16103185
TI  - A severe acute respiratory syndrome-associated coronavirus-specific protein
      enhances virulence of an attenuated murine coronavirus.
AB  - Most animal species that can be infected with the severe acute respiratory
      syndrome-associated coronavirus (SARS-CoV) do not reproducibly develop clinical
      disease, hindering studies of pathogenesis. To develop an alternative system for
      the study of SARS-CoV, we introduced individual SARS-CoV genes (open reading
      frames [ORFs]) into the genome of an attenuated murine coronavirus. One protein,
      the product of SARS-CoV ORF6, converted a sublethal infection to a uniformly
      lethal encephalitis and enhanced virus growth in tissue culture cells, indicating
      that SARS-CoV proteins function in the context of a heterologous coronavirus
      infection. Furthermore, these results suggest that the attenuated murine
      coronavirus lacks a virulence gene residing in SARS-CoV. Recombinant murine
      coronaviruses cause a reproducible and well-characterized clinical disease, offer
      virtually no risk to laboratory personnel, and should be useful for elucidating
      the role of SARS-CoV nonstructural proteins in viral replication and
      pathogenesis.

PMID- 16103186
TI  - Phylodynamic analysis of human immunodeficiency virus type 1 in distinct brain
      compartments provides a model for the neuropathogenesis of AIDS.
AB  - "Phylodynamic" analysis combines various statistical procedures that can be used
      to correlate the epidemiological and evolutionary behavior of viral pathogens
      with the immune system of the host. We utilized this approach to examine human
      immunodeficiency virus type 1 (HIV-1) gp120 envelope DNA sequences (V1, V2, and
      V3) isolated from different brain compartments of a T-cell-depleted patient
      diagnosed with severe HIV-associated dementia at the time of death. In agreement
      with previous reports, phylogenetic analysis showed distinct virodemes but also
      revealed a significant amount of viral gene flow among different brain
      compartments. Local-molecular-clock analysis showed that HIV-1 meninges and
      temporal lobe subpopulations evolve about 30 and 100 times faster, respectively,
      than the other viral populations in the brain. However, maximum likelihood codon
      based substitution models did not detect any site under significant positive
      selective pressure, and the main cause of HIV-1 genetic variation appeared to be
      random genetic drift. Therefore, the higher evolutionary rate in the meninges and
      temporal lobe could be due to an enhanced infection/expansion rate of macrophages
      as a consequence of the immune system failure. In conclusion, in this case study,
      viral infection in the brain progressed with a nonspecific genetic evolution,
      recurrent migration events, and an expansion of macrophage-tropic sequences. The
      data suggest that after immune failure newly produced viral variants, which would
      be rapidly cleared under normal conditions, begin to productively infect
      macrophages in a "self-amplifying" cycle of infection/inflammatory response that
      could be at the origin of HIV-associated dementia.

PMID- 16103187
TI  - Hepatitis C virus core protein is a dimeric alpha-helical protein exhibiting
      membrane protein features.
AB  - The building block of hepatitis C virus (HCV) nucleocapsid, the core protein,
      together with viral RNA, is composed of different domains involved in RNA binding
      and homo-oligomerization. The HCV core protein 1-169 (C(HCV)169) and its N
      terminal region from positions 1 to 117 (C(HCV)117) were expressed in Escherichia
      coli and purified to homogeneity suitable for biochemical and biophysical
      characterizations. The overall conformation and the oligomeric properties of the
      resulting proteins C(HCV)169 and C(HCV)117 were investigated by using analytical
      centrifugation, circular dichroism, intrinsic fluorescence measurements, and
      limited proteolysis. Altogether, our results show that core protein (C(HCV)169)
      behaves as a membranous protein and forms heterogeneous soluble micelle-like
      aggregates of high molecular weight in the absence of detergent. In contrast, it
      behaves, in the presence of mild detergent, as a soluble, well-folded,
      noncovalent dimer. Similar to findings observed for core proteins of HCV-related
      flaviviruses, the HCV core protein is essentially composed of alpha-helices
      (50%). In contrast, C(HCV)117 is soluble and monodispersed in the absence of
      detergent but is unfolded. It appears that the folding of the highly basic domain
      from positions 2 to 117 (2-117 domain) depends on the presence of the 117-169
      hydrophobic domain, which contains the structural determinants ensuring the
      binding of core with cellular membranes. Finally, our findings provide valuable
      information for further investigations on isolated core protein, as well as for
      attempts to reconstitute nucleocapsid particles in vitro.

PMID- 16103188
TI  - Human immunodeficiency virus type 1 Vpr-dependent cell cycle arrest through a
      mitogen-activated protein kinase signal transduction pathway.
AB  - The human immunodeficiency virus type 1 (HIV-1) Vpr protein has important
      functions in advancing HIV pathogenesis via several effects on the host cell. Vpr
      mediates nuclear import of the preintegration complex, induces host cell
      apoptosis, and inhibits cell cycle progression at G(2), which increases HIV gene
      expression. Some of Vpr's activities have been well described, but some
      functions, such as cell cycle arrest, are not yet completely characterized,
      although components of the ATR DNA damage repair pathway and the Cdc25C and Cdc2
      cell cycle control mechanisms clearly play important roles. We investigated the
      mechanisms underlying Vpr-mediated cell cycle arrest by examining global cellular
      gene expression profiles in cell lines that inducibly express wild-type and
      mutant Vpr proteins. We found that Vpr expression is associated with the down
      regulation of genes in the MEK2-ERK pathway and with decreased phosphorylation of
      the MEK2 effector protein ERK. Exogenous provision of excess MEK2 reverses the
      cell cycle arrest associated with Vpr, confirming the involvement of the MEK2-ERK
      pathway in Vpr-mediated cell cycle arrest. Vpr therefore appears to arrest the
      cell cycle at G(2)/M through two different mechanisms, the ATR mechanism and a
      newly described MEK2 mechanism. This redundancy suggests that Vpr-mediated cell
      cycle arrest is important for HIV replication and pathogenesis. Our findings
      additionally reinforce the idea that HIV can optimize the host cell environment
      for viral replication.

PMID- 16103189
TI  - Adenovirus type 5 E4orf3 protein targets the Mre11 complex to cytoplasmic
      aggresomes.
AB  - Virus infections have dramatic effects on structural and morphological
      characteristics of the host cell. The gene product of open reading frame 3 in the
      early region 4 (E4orf3) of adenovirus serotype 5 (Ad5) is involved in efficient
      replication and late protein synthesis. During infection with adenovirus mutants
      lacking the E4 region, the viral genomic DNA is joined into concatemers by
      cellular DNA repair factors, and this requires the Mre11/Rad50/Nbs1 complex.
      Concatemer formation can be prevented by the E4orf3 protein, which causes the
      cellular redistribution of the Mre11 complex. Here we show that E4orf3
      colocalizes with components of the Mre11 complex in nuclear tracks and also in
      large cytoplasmic accumulations. Rearrangement of Mre11 and Rad50 by Ad5 E4orf3
      is not dependent on interactions with Nbs1 or promyelocytic leukemia protein
      nuclear bodies. Late in infection the cytoplasmic inclusions appear as a distinct
      juxtanuclear accumulation at the centrosome and this requires an intact
      microtubule cytoskeleton. The large cytoplasmic accumulations meet the criteria
      defined for aggresomes, including gamma-tubulin colocalization and formation of a
      surrounding vimentin cage. E4orf3 also appears to alter the solubility of the
      cellular Mre11 complex. These data suggest that E4orf3 can target the Mre11
      complex to an aggresome and may explain how the cellular repair complex is
      inactivated during adenovirus infection.

PMID- 16103190
TI  - Examination of the pRb-dependent and pRb-independent functions of E7 in vivo.
AB  - High-risk human papillomaviruses encode two oncogenes, E6 and E7, expressed in
      nearly all cervical cancers. Although E7 protein is best known for its ability to
      inactivate the retinoblastoma tumor suppressor protein, pRb, many other
      activities for E7 have been proposed in in vitro studies. Herein, we describe
      studies that allowed us to define unambiguously the pRb-dependent and 
      independent activities of E7 for the first time in vivo. In these studies, we
      crossed mice transgenic for human papillomavirus 16 E7 to knock-in mice
      genetically engineered to express a mutant form of pRb (pRb(DeltaLXCXE)) that is
      selectively defective for binding E7. pRb inactivation was necessary for E7 to
      induce DNA synthesis and to overcome differentiation-dependent cell cycle
      withdrawal and DNA damage-induced cell cycle arrest. While most of E7's effects
      on epidermal differentiation were found to require pRb inactivation, a modest
      delay in terminal differentiation with resulting hyperplasia was observed in E7
      mice on the Rb(DeltaLXCXE) mutant background. E7-induced p21 upregulation was
      also pRb dependent, and genetic Rb inactivation was sufficient to reproduce this
      effect. While E7-mediated p21 induction was partially p53 dependent, neither p53
      nor p21 induction by E7 required p19(ARF). These data show that E7 upregulates
      the expression of p53 and p21 via pRb-dependent mechanisms distinct from the
      proposed p19-Mdm2 pathway. These results extend our appreciation of the
      importance of pRb as a relevant target for high-risk E7 oncoproteins.

PMID- 16103191
TI  - The secreted form of dengue virus nonstructural protein NS1 is endocytosed by
      hepatocytes and accumulates in late endosomes: implications for viral
      infectivity.
AB  - The flavivirus nonstructural protein NS1 is expressed as three discrete species
      in infected mammalian cells: an intracellular, membrane-associated form essential
      for viral replication, a cell surface-associated form that may be involved in
      signal transduction, and a secreted form (sNS1), the biological properties of
      which remain elusive. To determine the distribution of the dengue virus (DEN)
      sNS1 protein in vivo, we have analyzed by immunohistological means the tissue
      tropism of purified DEN sNS1 injected intravenously into adult mice. The sNS1
      protein was found predominantly associated with the liver, where hepatocytes
      appeared to represent a major target cell. We further showed that sNS1 could be
      efficiently endocytosed by human Huh7 and HepG2 hepatocytes in vitro. After its
      internalization, the protein was detected intracellularly for at least 48 h
      without being substantially degraded. Colocalization studies of sNS1 with markers
      of the endolysosomal compartments revealed that the protein was specifically
      targeted to lysobisphosphatidic acid-rich structures reminiscent of late
      endosomes, as confirmed by electron microscopy. Intracellular accumulation of
      sNS1 in Huh7 cells enhanced the fluid phase uptake of rhodamine-labeled dextran.
      Furthermore, preincubation of Huh7 cells with sNS1 increased dengue virus
      production after infection with the homologous strain of DEN-1 virus. Our results
      demonstrate that the accumulation of DEN sNS1 in the late endosomal compartment
      of hepatocytes potentializes subsequent dengue virus infection in vitro, raising
      the possibility that sNS1 may contribute to viral propagation in vivo.

PMID- 16103192
TI  - H5N2 avian influenza outbreak in Texas in 2004: the first highly pathogenic
      strain in the United States in 20 years?
AB  - In early 2004, an H5N2 avian influenza virus (AIV) that met the molecular
      criteria for classification as a highly pathogenic AIV was isolated from chickens
      in the state of Texas in the United States. However, clinical manifestations in
      the affected flock were consistent with avian influenza caused by a low
      pathogenicity AIV and the representative virus (A/chicken/Texas/298313/04
      [TX/04]) was not virulent for experimentally inoculated chickens. The
      hemagglutinin (HA) gene of the TX/04 isolate was similar in sequence to
      A/chicken/Texas/167280-4/02 (TX/02), a low-pathogenicity AIV isolate recovered
      from chickens in Texas in 2002. However, the TX/04 isolate had one additional
      basic amino acid at the HA cleavage site, which could be attributed to a single
      point mutation. The TX/04 isolate was similar in sequence to TX/02 isolate in
      several internal genes (NP, M, and NS), but some genes (PA, PB1, and PB2) had
      sequence of a clearly different origin. The TX/04 isolate also had a stalk
      deletion in the NA gene, characteristic of a chicken-adapted AIV. By analyzing
      viruses constructed by in vitro mutagenesis followed by reverse genetics, we
      found that the pathogenicity of the TX/04 virus could be increased in vitro and
      in vivo by the insertion of an additional basic amino acid at the HA cleavage
      site and not by the loss of a glycosylation site near the cleavage site. Our
      study provides the genetic and biologic characteristics of the TX/04 isolate,
      which highlight the complexity of the polygenic nature of the virulence of
      influenza viruses.

PMID- 16103193
TI  - Human immunodeficiency virus Nef induces rapid internalization of the T-cell
      coreceptor CD8alphabeta.
AB  - Human immunodeficiency virus (HIV) Nef is a membrane-associated protein
      decreasing surface expression of CD4, CD28, and major histocompatibility complex
      class I on infected cells. We report that Nef strongly down-modulates surface
      expression of the beta-chain of the CD8alphabeta receptor by accelerated
      endocytosis, while CD8 alpha-chain expression is less affected. By mutational
      analysis of the cytoplasmic tail of the CD8 beta-chain, an FMK amino acid motif
      was shown to be critical for Nef-induced endocytosis. Although independent of
      CD4, endocytosis of the CD8 beta-chain was abrogated by the same mutations in Nef
      that affect CD4 down-regulation, suggesting common molecular interactions. The
      ability to down-regulate the human CD8 beta-chain was conserved in HIV-1, HIV-2,
      and simian immunodeficiency virus SIVmac239 Nef and required an intact AP-2
      complex. The Nef-mediated internalization of receptors, such as CD4, major
      histocompatibility complex class I, CD28, and CD8alphabeta, may contribute to the
      subversion of the host immune system and progression towards AIDS.

PMID- 16103194
TI  - Large-scale analysis of adeno-associated virus vector integration sites in normal
      human cells.
AB  - The integration sites of viral vectors used in human gene therapy can have
      important consequences for safety and efficacy. However, an extensive evaluation
      of adeno-associated virus (AAV) vector integration sites has not been completed,
      despite the ongoing use of AAV vectors in clinical trials. Here we have used a
      shuttle vector system to isolate and analyze 977 unique AAV vector-chromosome
      integration junctions from normal human fibroblasts and describe their genomic
      distribution. We found a significant preference for integrating within CpG
      islands and the first 1 kb of genes, but only a slight overall preference for
      transcribed sequences. Integration sites were clustered throughout the genome,
      including a major preference for integration in ribosomal DNA repeats, and 13
      other hotspots that contained three or more proviruses within a 500-kb window.
      Both junctions were localized from 323 proviruses, allowing us to characterize
      the chromosomal deletions, insertions, and translocations associated with vector
      integration. These studies establish a profile of insertional mutagenesis for AAV
      vectors and provide unique insight into the chromosomal distribution of DNA
      strand breaks that may facilitate integration.

PMID- 16103195
TI  - Radiation leukemia virus common integration at the Kis2 locus: simultaneous
      overexpression of a novel noncoding RNA and of the proximal Phf6 gene.
AB  - Retroviral tagging has been used extensively and successfully to identify genes
      implicated in cancer pathways. In order to find oncogenes implicated in T-cell
      leukemia, we used the highly leukemogenic radiation leukemia retrovirus VL3
      (RadLV/VL3). We applied the inverted PCR technique to isolate and analyze
      sequences flanking proviral integrations in RadLV/VL3-induced T lymphomas. We
      found retroviral integrations in c-myc and Pim1 as already reported but we also
      identified for the first time Notch1 as a RadLV common integration site. More
      interestingly, we found a new RadLV common integration site that is situated on
      mouse chromosome X (XA4 region, bp 45091000). This site has also been reported as
      an SL3-3 and Moloney murine leukemia virus integration site, which strengthens
      its implication in murine leukemia virus-induced T lymphomas. This locus, named
      Kis2 (Kaplan Integration Site 2), was found rearranged in 11% of the tumors
      analyzed. In this article, we report not only the alteration of the Kis2 gene
      located nearby in response to RadLV integration but also the induction of the
      expression of Phf6, situated about 250 kbp from the integration site. The Kis2
      gene encodes five different alternatively spliced noncoding RNAs and the Phf6
      gene codes for a 365-amino-acid protein which contains two plant homology domain
      fingers, recently implicated in the Borjeson-Forssman-Lehmann syndrome in humans.
      With the recent release of the mouse genome sequence, high-throughput retroviral
      tagging emerges as a powerful tool in the quest for oncogenes. It also allows the
      analysis of large DNA regions surrounding the integration locus.

PMID- 16103196
TI  - Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus
      encephalitis.
AB  - The activation and entry of antigen-specific CD8(+) T cells into the central
      nervous system is an essential step towards clearance of West Nile virus (WNV)
      from infected neurons. The molecular signals responsible for the directed
      migration of virus-specific T cells and their cellular sources are presently
      unknown. Here we demonstrate that in response to WNV infection, neurons secrete
      the chemokine CXCL10, which recruits effector T cells via the chemokine receptor
      CXCR3. Neutralization or a genetic deficiency of CXCL10 leads to a decrease in
      CXCR3(+) CD8(+) T-cell trafficking, an increase in viral burden in the brain, and
      enhanced morbidity and mortality. These data support a new paradigm in chemokine
      neurobiology, as neurons are not generally considered to generate antiviral
      immune responses, and CXCL10 may represent a novel neuroprotective agent in
      response to WNV infection in the central nervous system.

PMID- 16103198
TI  - The severe acute respiratory syndrome coronavirus nucleocapsid protein is
      phosphorylated and localizes in the cytoplasm by 14-3-3-mediated translocation.
AB  - The severe acute respiratory syndrome coronavirus(SARS-CoV) nucleocapsid (N)
      protein is one of the four structural proteins of the virus and is predicted to
      be a 46-kDa phosphoprotein. Our in silico analysis predicted N to be heavily
      phosphorylated at multiple residues. Experimentally, we have shown in this report
      that the N protein of the SARS-CoV gets serine-phosphorylated by multiple
      kinases, in both the cytoplasm and the nucleus. The phosphoprotein is stable and
      localizes in the cytoplasm and coprecipitates with the membrane fraction. Also,
      using specific inhibitors of phosphorylation and an in vitro phosphorylation
      assay, we show that the nucleocapsid protein is a substrate of cyclin-dependent
      kinase (CDK), glycogen synthase kinase, mitogen-activated protein kinase, and
      casein kinase II. Further, we show that the phosphorylated protein is
      translocated to the cytoplasm by binding to 14-3-3 (tyrosine 3
      monooxygenase/tryptophan 5-monooxygenase activation protein). 14-3-3 proteins are
      a family of highly conserved, ubiquitously expressed eukaryotic proteins that
      function primarily as adapters that modulate interactions between components of
      various cellular signaling and cell cycle regulatory pathways through
      phosphorylation-dependent protein-protein interactions. Coincidentally, the N
      protein was also found to downregulate the expression of the theta isoform of 14
      3-3 (14-3-3theta), leading to the accumulation of phosphorylated N protein in the
      nucleus, in the absence of growth factors. Using short interfering RNA specific
      to 14-3-3theta we have inhibited its expression to show accumulation of
      phosphorylated N protein in the nucleus. Thus, the data presented here provide a
      possible mechanism for phosphorylation-dependent nucleocytoplasmic shuttling of
      the N protein. This 14-3-3-mediated transport of the phosphorylated N protein and
      its possible implications in interfering with the cellular machinery are
      discussed.

PMID- 16103197
TI  - Human cytomegalovirus IE1-72 activates ataxia telangiectasia mutated kinase and a
      p53/p21-mediated growth arrest response.
AB  - Human cytomegalovirus (HCMV) encodes several proteins that can modulate
      components of the cell cycle machinery. The UL123 gene product, IE1-72, binds the
      Rb-related, p107 protein and relieves its repression of E2F-responsive promoters;
      however, it is unable to induce quiescent cells to enter S phase in wild-type
      (p53(+/+)) cells. IE1-72 also induces p53 accumulation through an unknown
      mechanism. We present here evidence suggesting that IE1-72 may activate the p53
      pathway by increasing the levels of p19(Arf) and by inducing the phosphorylation
      of p53 at Ser15. Phosphorylation of this residue by IE1-72 expression alone or
      HCMV infection is found to be dependent on the ataxia-telangiectasia mutated
      kinase. IE2-86 expression leads to p53 phosphorylation and may contribute to this
      phenotype in HCMV-infected cells. We also found that IE1-72 promotes p53 nuclear
      accumulation by abrogating p53 nuclear shuttling. These events result in the
      stimulation of p53 activity, leading to a p53- and p21-dependent inhibition of
      cell cycle progression from G(1) to S phase in cells transiently expressing IE1
      72. Thus, like many of the small DNA tumor viruses, the first protein expressed
      upon HCMV infection activates a p53 response by the host cell.

PMID- 16103199
TI  - Assembly and intracellular localization of the bluetongue virus core protein VP3.
AB  - The bluetongue virus (BTV) core protein VP3 plays a crucial role in the virion
      assembly and replication process. Although the structure of the protein is well
      characterized, much less is known about the intracellular processing and
      localization of the protein in the infected host cell. In BTV-infected cells,
      newly synthesized viral core particles accumulate in specific locations within
      the host cell in structures known as virus inclusion bodies (VIBs), which are
      composed predominantly of the nonstructural protein NS2. However, core protein
      location in the absence of VIBs remains unclear. In this study, we examined VP3
      location and degradation both in the absence of any other viral protein and in
      the presence of NS2 or the VP3 natural associate protein, VP7. To enable real
      time tracking and processing of VP3 within the host cell, a fully functional
      enhanced green fluorescent protein (EGFP)-VP3 chimera was synthesized, and
      distribution of the fusion protein was monitored in different cell types using
      specific markers and inhibitors. In the absence of other BTV proteins, EGFP-VP3
      exhibited distinct cytoplasmic focus formation. Further evidence suggested that
      EGFP-VP3 was targeted to the proteasome of the host cells but was dispersed
      throughout the cytoplasm when MG132, a specific proteasome inhibitor, was added.
      However, the distribution of the chimeric EGFP-VP3 protein was altered
      dramatically when the protein was expressed in the presence of the BTV core
      protein VP7, a normal partner of VP3 during BTV assembly. Interaction of EGFP-VP3
      and VP7 and subsequent assembly of core-like particles was further examined by
      visualizing fluorescent particles and was confirmed by biochemical analysis and
      by electron microscopy. These data indicated the correct assembly of EGFP-VP3
      subcores, suggesting that core formation could be monitored in real time. When
      EGFP-VP3 was expressed in BTV-infected BSR cells, the protein was not associated
      with proteasomes but instead was distributed within the BTV inclusion bodies,
      where it colocalized with NS2. These findings expand our knowledge about VP3
      localization and its fate within the host cell and illustrate the assembly
      capability of a VP3 molecule with a large amino-terminal extension. This also
      opens up the possibility of application as a delivery system.

PMID- 16103200
TI  - Enhancement of enveloped virus entry by phosphatidylserine.
AB  - Enveloped virus vectors are used in a wide variety of applications. We have
      discovered that treatment of cultured cells with phosphatidylserine (PS)
      liposomes can increase virus vector infection by up to 20-fold. This effect does
      not abrogate virus receptor requirements, is specific to PS compared to other
      phospholipids, and is limited to enveloped viruses. Furthermore, the enhancement
      of infection does not occur through increases in virus receptor levels or virus
      binding, indicating that virus fusion is enhanced. The liposomes are easily
      generated, store well, and allow enhanced infection with a variety of virus
      vectors and cell types.

PMID- 16103201
TI  - Replication of varicella-zoster virus in human skin organ culture.
AB  - Varicella-zoster virus (VZV) infection is restricted to humans, which hinders
      studies of its pathogenesis in rodent models of disease. To facilitate the study
      of VZV skin tropism, we developed an ex vivo system using human fetal skin organ
      culture (SOC). VZV replication was analyzed by plaque assay, transmission
      electron microscopy, and histology. The yield of infectious VZV from SOC
      increased approximately 100-fold over 6 days, virions were abundant, and lesions
      developed that contained VZV antigens and resembled varicella and zoster lesions.
      The SOC system for VZV replication has applications for testing virus mutants and
      antiviral drugs.

PMID- 16103202
TI  - Intracellular localization of the severe acute respiratory syndrome coronavirus
      nucleocapsid protein: absence of nucleolar accumulation during infection and
      after expression as a recombinant protein in vero cells.
AB  - The nucleocapsid (N) protein of several members within the order Nidovirales
      localizes to the nucleolus during infection and after transfection of cells with
      N genes. However, confocal microscopy of N protein localization in Vero cells
      infected with the severe acute respiratory syndrome coronavirus (SARS-CoV) or
      transfected with the SARS-CoV N gene failed to show the presence of N in the
      nucleoplasm or nucleolus. Amino acids 369 to 389, which contain putative nuclear
      localization signal (NLS) and nucleolar localization signal motifs, failed to
      restore nuclear localization to an NLS-minus mutant Rev protein. These data
      indicate that nuclear localization is not a conserved property among all
      nidoviruses.

PMID- 16103203
TI  - APOBEC3G/CEM15 (hA3G) mRNA levels associate inversely with human immunodeficiency
      virus viremia.
AB  - APOBEC3G/CEM15 (hA3G) is a novel host factor that confers resistance to
      lentiviral infection under experimental conditions. Human immunodeficiency virus
      (HIV) type 1, however, produces viral infectivity factor (Vif) that targets hA3G
      for proteolysis, thereby escaping this defense system. To examine hA3G's
      contribution to the protection against HIV disease progression in humans, we
      quantified hA3G mRNA levels in peripheral blood mononuclear cells from 6 HIV
      uninfected and 25 HIV-infected subjects; the latter group included 8 long-term
      nonprogressors (LTNPs) and 17 progressors. None of the HIV-infected subjects were
      receiving antiretroviral therapy. We found a striking inverse correlation between
      hA3G mRNA levels and HIV viral loads (P < or = 0.00009) and a highly significant
      positive correlation between hA3G mRNA levels and CD4 cell counts (P < or =
      0.00012) in these patients. Furthermore, we discovered that the order of hA3G
      mRNA levels is LTNPs > HIV-uninfected subjects > progressors.

PMID- 16103204
TI  - Identification of quantitative trait loci for susceptibility to mouse adenovirus
      type 1.
AB  - Adult SJL/J mice are highly susceptible to mouse adenovirus type 1 (MAV-1)
      infections, whereas other inbred strains, including BALB/cJ, are resistant (K. R.
      Spindler, L. Fang, M. L. Moore, C. C. Brown, G. N. Hirsch, and A. K. Kajon, J.
      Virol. 75:12039-12046, 2001). Using congenic mouse strains, we showed that the H
      2(s) haplotype of SJL/J mice is not associated with susceptibility to MAV-1.
      Susceptibility of MAV-1-infected (BALB/cJ x SJL/J)F(1) mice was intermediate
      between that of SJL/J mice and that of BALB/cJ mice, indicating that
      susceptibility is a genetically controlled quantitative trait. We mapped genetic
      loci involved in mouse susceptibility to MAV-1 by analysis of 192 backcross
      progeny in a genome scan with 65 simple sequence length polymorphic markers. A
      major quantitative trait locus (QTL) was detected on chromosome 15 (Chr 15) with
      a highly significant logarithm of odds score of 21. The locus on Chr 15 alone
      accounts for 40% of the total trait variance between susceptible and resistant
      strains. QTL modeling of the data indicated that there are a number of other QTLs
      with small effects that together with the major QTL on Chr 15 account for 54% of
      the trait variance. Identification of the major QTL is the first step in
      characterizing host genes involved in susceptibility to MAV-1.

PMID- 16103205
TI  - Human immunodeficiency virus mutations during the first month of infection are
      preferentially found in known cytotoxic T-lymphocyte epitopes.
AB  - The full protein coding region of human immunodeficiency virus (HIV) genomes were
      sequenced using plasma collected from nine African-Americans prior to
      seroconversion and 7 to 28 days later. HIV mutations emerged in seven of these
      subjects at a genomewide rate of 2% per year. The location of nonsynonymous (NS)
      HIV mutations within these subjects was compared to their potential HLA-A and B
      types restricted CTL epitopes reported in the Los Alamos National Laboratory HIV
      immunology database. A statistically significant (P < 0.005) number of the early
      NS mutations (13.5%) were found within previously reported CTL epitopes. A virus
      sequencing and reported CTL epitopes database analysis therefore support a model
      where a significant proportion of very early nonsynonymous HIV mutations are
      selected by CTL.

PMID- 16103206
TI  - Reversion in vivo after inoculation of a molecular proviral DNA clone of simian
      immunodeficiency virus with a cytotoxic-T-lymphocyte escape mutation.
AB  - Vaccine-based control of the replication of a simian immunodeficiency virus
      (SIV), SIVmac239, in macaques has recently been shown. In the process of the
      control, a mutant virus escaping from epitope-specific cytotoxic-T-lymphocyte
      (CTL) responses was rapidly selected and contained. In this study, we show that
      the wild-type virus appeared and became predominant in the absence of the epitope
      specific CTL after inoculation of naive macaques with a molecular clone DNA of
      the CTL escape mutant SIV. This is the first report describing reversion in vivo
      from an inoculated, molecular proviral DNA clone of immunodeficiency virus with a
      CTL escape mutation.

PMID- 16103207
TI  - A single amino acid substitution in 1918 influenza virus hemagglutinin changes
      receptor binding specificity.
AB  - The receptor binding specificity of influenza viruses may be important for host
      restriction of human and avian viruses. Here, we show that the hemagglutinin (HA)
      of the virus that caused the 1918 influenza pandemic has strain-specific
      differences in its receptor binding specificity. The A/South Carolina/1/18 HA
      preferentially binds the alpha2,6 sialic acid (human) cellular receptor, whereas
      the A/New York/1/18 HA, which differs by only one amino acid, binds both the
      alpha2,6 and the alpha2,3 sialic acid (avian) cellular receptors. Compared to the
      conserved consensus sequence in the receptor binding site of avian HAs, only a
      single amino acid at position 190 was changed in the A/New York/1/18 HA. Mutation
      of this single amino acid back to the avian consensus resulted in a preference
      for the avian receptor.

PMID- 16103208
TI  - Long-term presence of virus-specific plasma cells in sensory ganglia and spinal
      cord following intravaginal inoculation of herpes simplex virus type 2.
AB  - The tissue sites of long-term herpes simplex virus type 2 (HSV-2)-specific
      antibody production in mice and guinea pigs were identified. In addition to
      secondary lymphoid tissue and bone marrow, HSV-specific plasma cells were
      detected in spinal cords of mice up to 10 months after intravaginal inoculation
      with a thymidine kinase-deficient HSV-2 strain and in lumbosacral ganglia and
      spinal cords of guinea pigs inoculated with HSV-2 strain MS. The long-term
      retention of virus-specific plasma cells in the peripheral and central nervous
      systems following HSV infection may be important for resistance to reinfection of
      neuronal tissues or may play a role in modulation of reactivation from latency.

PMID- 16103209
TI  - Importin 7 may be dispensable for human immunodeficiency virus type 1 and simian
      immunodeficiency virus infection of primary macrophages.
AB  - In an in vitro assay employing reconstituted nuclei, importin 7 (IPO7) has been
      implicated in nuclear translocation of human immunodeficiency virus type 1 (HIV
      1) cDNA. Using RNA interference technology, we inhibited expression of IPO7 by 80
      to 95% in primary macrophages and in HeLa cells and monitored their ability to
      support HIV-1 and simian immunodeficiency virus (SIV) cDNA synthesis, nuclear
      translocation, and infection efficiency. Marked IPO7 deficiency did not alter the
      rate or extent of HIV-1 or SIV cDNA synthesis or nuclear translocation. The
      infection efficiency of HIV-1 was similarly unaltered. Therefore, in natural,
      nondividing targets of HIV-1, IPO7 may be dispensable for infection.

PMID- 16103210
TI  - Relative contributions of measles virus hemagglutinin- and fusion protein
      specific serum antibodies to virus neutralization.
AB  - The relative contribution of measles virus hemagglutinin (H)- or fusion protein
      (F)-specific antibodies to virus neutralization (VN) has not been demonstrated.
      We have depleted these specific antibodies from sera collected from young adults,
      who had been vaccinated during childhood, by prolonged incubation with viable
      transfected human melanoma cells expressing H or F. Simultaneous depletion of
      antibodies of both specificities completely abrogated VN activity. Depletion of F
      specific antibodies only had a minimal effect, whereas removal of H-specific
      antibodies resulted in almost complete reduction of VN activity. These results
      demonstrate that measles virus neutralizing antibodies are mainly directed to the
      H protein.

PMID- 16103211
TI  - The love-hate relationship between Ras and Notch.
AB  - The Ras and Notch signaling pathways are used over and over again during
      development to control many different biological processes. Frequently, these two
      signaling pathways intersect to influence common processes, but sometimes they
      cooperate and sometimes they antagonize each other. The Caenorhabditis elegans
      vulva and the Drosophila eye are two classic paradigms for understanding how Ras
      and Notch affect cell fates, and how the two pathways work together to control
      biological pattern. Recent advances in these systems reveal some of the
      mechanisms by which Ras and Notch can interact. Similar types of interactions in
      mammals may be important for determining whether and how alterations in Ras or
      Notch lead to cancer.

PMID- 16103212
TI  - 4E-BP functions as a metabolic brake used under stress conditions but not during
      normal growth.
AB  - 4E-BP is an important regulator of overall translation levels in cells. By
      binding eIF4E, 4E-BP impairs recruitment of the 40S ribosomal subunit to the cap
      structure present at the 5'-end of all eukaryotic cellular mRNAs. 4E-BP activity
      is controlled by TOR (Target of Rapamycin). 4E-BP has been studied extensively in
      cell culture; however, the biological role of 4E-BP in developing organisms is
      unclear to date. Since TOR has been shown to control tissue growth during animal
      development, 4E-BP has also been assumed to serve as a growth regulator. Here, we
      study the relevance of 4E-BP function for organismal development, and present
      evidence for an alternate view. We show that 4E-BP strongly affects fat
      metabolism in Drosophila. We suggest that 4E-BP works as a metabolic brake that
      is activated under conditions of environmental stress to control fat metabolism.
      4E-BP mutants lack this regulation, reducing their ability to survive under
      unfavorable conditions.

PMID- 16103213
TI  - Control of liver cell fate decision by a gradient of TGF beta signaling modulated
      by Onecut transcription factors.
AB  - During liver development, hepatocytes and biliary cells differentiate from common
      progenitors called hepatoblasts. The factors that control hepatoblast fate
      decision are unknown. Here we report that a gradient of activin/TGFbeta signaling
      controls hepatoblast differentiation. High activin/TGFbeta signaling is required
      near the portal vein for differentiation of biliary cells. The Onecut
      transcription factors HNF-6 and OC-2 inhibit activin/TGFbeta signaling in the
      parenchyma, and this allows normal hepatocyte differentiation. In the absence of
      Onecut factors, the shape of the activin/TGFbeta gradient is perturbed and the
      hepatoblasts differentiate into hybrid cells that display characteristics of both
      hepatocytes and biliary cells. Thus, a gradient of activin/TGFbeta signaling
      modulated by Onecut factors is required to segregate the hepatocytic and the
      biliary lineages.

PMID- 16103214
TI  - Transcription switches for protoxylem and metaxylem vessel formation.
AB  - Land plants evolved xylem vessels to conduct water and nutrients, and to support
      the plant. Microarray analysis with a newly established Arabidopsis in vitro
      xylem vessel element formation system and promoter analysis revealed the possible
      involvement of some plant-specific NAC-domain transcription factors in xylem
      formation. VASCULAR-RELATED NAC-DOMAIN6 (VND6) and VND7 can induce
      transdifferentiation of various cells into metaxylem- and protoxylem-like vessel
      elements, respectively, in Arabidopsis and poplar. A dominant repression of VND6
      and VND7 specifically inhibits metaxylem and protoxylem vessel formation in
      roots, respectively. These findings suggest that these genes are transcription
      switches for plant metaxylem and protoxylem vessel formation.

PMID- 16103215
TI  - The growing pre-mRNA recruits actin and chromatin-modifying factors to
      transcriptionally active genes.
AB  - In the dipteran Chironomus tentans, actin binds to hrp65, a nuclear protein
      associated with mRNP complexes. Disruption of the actin-hrp65 interaction in vivo
      by the competing peptide 65-2CTS reduces transcription drastically, which
      suggests that the actin-hrp65 interaction is required for transcription. We show
      that the inhibitory effect of the 65-2CTS peptide on transcription is
      counteracted by trichostatin A, a drug that inhibits histone deacetylation. We
      also show that actin and hrp65 are associated in vivo with p2D10, an
      evolutionarily conserved protein with histone acetyltransferase activity that
      acts on histone H3. p2D10 is recruited to class II genes in a transcription
      dependent manner. We show, using the Balbiani ring genes of C. tentans as a model
      system, that p2D10 is cotranscriptionally associated with the growing pre-mRNA.
      We also show that experimental disruption of the actin-hrp65 interaction by the
      65-2CTS peptide in vivo results in the release of p2D10 from the transcribed
      genes, reduced histone H3 acetylation, and a lower level of transcription
      activity. Furthermore, antibodies against p2D10 inhibit run-on elongation. Our
      results suggest that actin, hrp65, and p2D10 are parts of a positive feedback
      mechanism that contributes to maintaining the active transcription state of a
      gene by recruiting HATs at the RNA level.

PMID- 16103216
TI  - Methylation of histone H4 by arginine methyltransferase PRMT1 is essential in
      vivo for many subsequent histone modifications.
AB  - PRMT1 is a histone methyltransferase that methylates Arg3 on histone H4. When we
      used siRNA to knock down PRMT1 in an erythroid cell line, it resulted in nearly
      complete loss of H4 Arg3 methylation across the chicken beta-globin domain, which
      we use as a model system for studying the relationship of gene activity to
      histone modification. We observed furthermore a domain-wide loss of histone
      acetylation on both histones H3 and H4, as well as an increase in H3 Lys9 and
      Lys27 methylation, both marks associated with inactive chromatin. To determine
      whether the effect on acetylation was directly related to the loss of H4 Arg3
      methylation, we performed an in vitro acetylation reaction on chromatin isolated
      from PRMT1-depleted cells. We found that nucleosomes purified from these cells,
      and depleted in methylation at Arg3, are readily acetylated by nuclear extracts
      from the same cells, if and only if the nucleosomes are incubated with PRMT1
      beforehand. Thus, methylation of histones by PRMT1 was sufficient to permit
      subsequent acetylation. Consistent with earlier reports of experiments in vitro,
      H4 Arg3 methylation by PRMT1 appears to be essential in vivo for the
      establishment or maintenance of a wide range of "active" chromatin modifications.

PMID- 16103217
TI  - The Isy1p component of the NineTeen complex interacts with the ATPase Prp16p to
      regulate the fidelity of pre-mRNA splicing.
AB  - Prp16p is a DEAH-box ATPase that transiently associates with the spliceosome to
      promote the structural transition required for the second chemical step. Yeast
      strains carrying the cold-sensitive allele prp16-302 stall the release of Prp16p
      at low temperatures, yet splice precursors with aberrant branchpoints at
      increased frequency. To identify new factors involved in the regulation of
      splicing fidelity, we sought suppressors of the prp16-302 growth phenotype.
      Deletion of the nonessential ISY1 gene (1) improves growth of prp16-302 strains,
      (2) alleviates stalling, and (3) restores fidelity of branchpoint usage to wild
      type levels. Isy1p is a subunit of the NineTeen Complex containing Prp19p, an
      essential E3 ubiquitin ligase homolog required for splicing. Notably, Deltaisy1
      PRP16 strains display reduced fidelity of 3'-splice site selection. Consistent
      with a recent two-state model of the spliceosome, our genetic and biochemical
      results suggest that Isy1p acts together with U6 snRNA to promote a spliceosomal
      conformation favorable for first-step chemistry. We propose that deletion of ISY1
      favors the premature release of Prp16p, thus promoting second-step chemistry of
      precursors with inappropriate 3'-splice sites.

PMID- 16103218
TI  - Molecular anatomy and regulation of a stable replisome at a paused eukaryotic DNA
      replication fork.
AB  - Eukaryotic cells regulate the progression and integrity of DNA replication forks
      to maintain genomic stability and couple DNA synthesis to other processes. The
      budding yeast proteins Mrc1 and Tof1 associate with the putative MCM-Cdc45
      helicase and limit progression of the replisome when nucleotides are depleted,
      and the checkpoint kinases Mec1 and Rad53 stabilize such stalled forks and
      prevent disassembly of the replisome. Forks also pause transiently during
      unperturbed chromosome replication, at sites where nonnucleosomal proteins bind
      DNA tightly. We describe a method for inducing prolonged pausing of forks at
      protein barriers assembled at unique sites on a yeast chromosome, allowing us to
      examine for the first time the effects of pausing upon replisome integrity. We
      show that paused forks maintain an intact replisome that contains Mrc1, Tof1, MCM
      Cdc45, GINS, and DNA polymerases alpha and epsilon and that recruits the Rrm3
      helicase. Surprisingly, pausing does not require Mrc1, although Tof1 and Csm3 are
      both important. In addition, the integrity of the paused forks does not require
      Mec1, Rad53, or recombination. We also show that paused forks at analogous
      barriers in the rDNA are regulated similarly. These data indicate that paused and
      stalled eukaryotic replisomes resemble each other but are regulated differently.

PMID- 16103219
TI  - Control of dTTP pool size by anaphase promoting complex/cyclosome is essential
      for the maintenance of genetic stability.
AB  - Anaphase promoting complex/cyclosome (APC/C)-mediated proteolysis is essential
      for chromosome segregation, mitotic exit, and G1 entry. Here, we show the
      importance of APC/C in the control of dTTP pool size in mammalian cells. Two
      enzymes, thymidine kinase 1 (TK1) and thymidylate kinase (TMPK), involved in dTTP
      formation are the targets of the APC/C pathway. We demonstrate that TMPK is
      recognized and degraded by APC/C-Cdc20/Cdh1-mediated pathways from mitosis to the
      early G1 phase, whereas TK1 is targeted for degradation by APC/C-Cdh1 after
      mitotic exit. Overexpression of wild-type TK1 and TMPK induces a four- to
      fivefold increase in the cellular dTTP pool without promoting spontaneous
      mutations in the hprt (hypoxanthine-guanine phosphoribosyl transferase) gene. In
      contrast, coexpression of nondegradable TK1 and TMPK expands the dTTP pool size
      10-fold accompanied by a drastic dNTP pool imbalance. Most interestingly,
      disruption of APC/C proteolysis of TK1 and TMPK leads to growth retardation and a
      striking increase in gene mutation rate. We conclude that down-regulation of dTTP
      pool size by the APC/C pathway during mitosis and the G1 phase is an essential
      means to maintain a balanced dNTP pool and to avoid genetic instability.

PMID- 16103220
TI  - Deregulated matriptase causes ras-independent multistage carcinogenesis and
      promotes ras-mediated malignant transformation.
AB  - Overexpression of the type II transmembrane serine protease matriptase is a
      highly consistent feature of human epithelial tumors. Here we show that
      matriptase possesses a strong oncogenic potential when unopposed by its
      endogenous inhibitor, HAI-1. Modest orthotopic overexpression of matriptase in
      the skin of transgenic mice caused spontaneous squamous cell carcinoma and
      dramatically potentiated carcinogen-induced tumor formation. Matriptase-induced
      malignant conversion was preceded by progressive interfollicular hyperplasia,
      dysplasia, follicular transdifferentiation, fibrosis, and dermal inflammation.
      Furthermore, matriptase induced activation of the pro-tumorigenic PI3K-Akt
      signaling pathway. This activation was frequently accompanied by H-ras or K-ras
      mutations in carcinogen-induced tumors, whereas matriptase-induced spontaneous
      carcinoma formation occurred independently of ras activation. Increasing
      epidermal HAI-1 expression completely negated the oncogenic effects of
      matriptase. The data implicate dysregulated matriptase expression in malignant
      epithelial transformation.

PMID- 16103221
TI  - Dendrite development: a surprising origin.
AB  - Neurons extend elaborate dendrites studded with spines. Unexpectedly, this
      cellular sculpting is regulated by the origin recognition complex -- the core
      machinery for initiating DNA replication.

PMID- 16103222
TI  - FAPP2 is involved in the transport of apical cargo in polarized MDCK cells.
AB  - Phosphatidylinositol-4-phosphate (PI(4)P) is the main phosphoinositide in the
      Golgi complex and has been reported to play a pleiotropic role in transport of
      cargo from the trans-Golgi network to the plasma membrane (PM) in polarized Madin
      Darby canine kidney (MDCK) cells. Overexpression of the chimeric fluorescent
      protein encoding the pleckstrin homology domain, which is specific for PI(4)P,
      inhibited both apical and basolateral transport pathways. The transport of apical
      cargo from the Golgi was shown to be specifically decreased by adenovirus
      mediated RNA interference directed against PI(4)P adaptor protein (FAPP) 2. FAPP1
      depletion had no effect on transport. On the other hand, FAPP2 was not involved
      in the Golgi-to-PM transport of cargo that was targeted to the basolateral
      membrane domain. Thus, we conclude that FAPP2 plays a specific role in apical
      transport in MDCK cells.

PMID- 16103223
TI  - A glue for heterochromatin maintenance: stable SUV39H1 binding to heterochromatin
      is reinforced by the SET domain.
AB  - Trimethylation of histone H3 lysine 9 and the subsequent binding of
      heterochromatin protein 1 (HP1) mediate the formation and maintenance of
      pericentromeric heterochromatin. Trimethylation of H3K9 is governed by the
      histone methyltransferase SUV39H1. Recent studies of HP1 dynamics revealed that
      HP1 is not a stable component of heterochromatin but is highly mobile (Cheutin,
      T., A.J. McNairn, T. Jenuwein, D.M. Gilbert, P.B. Singh, and T. Misteli. 2003.
      Science. 299:721-725; Festenstein, R., S.N. Pagakis, K. Hiragami, D. Lyon, A.
      Verreault, B. Sekkali, and D. Kioussis. 2003. Science. 299:719-721). Because the
      mechanism by which SUV39H1 is recruited to and interacts with heterochromatin is
      unknown, we studied the dynamic properties of SUV39H1 in living cells by using
      fluorescence recovery after photobleaching and fluorescence resonance energy
      transfer. Our results show that a substantial population of SUV39H1 is immobile
      at pericentromeric heterochromatin, suggesting that, in addition to its catalytic
      activity, SUV39H1 may also play a structural role at pericentromeric regions.
      Analysis of SUV39H1 deletion mutants indicated that the SET domain mediates this
      stable binding. Furthermore, our data suggest that the recruitment of SUV39H1 to
      heterochromatin is at least partly independent from that of HP1 and that HP1
      transiently interacts with SUV39H1 at heterochromatin.

PMID- 16103224
TI  - Cyclic AMP and calcium interplay as second messengers in melatonin-dependent
      regulation of Plasmodium falciparum cell cycle.
AB  - The host hormone melatonin increases cytoplasmic Ca(2+) concentration and
      synchronizes Plasmodium cell cycle (Hotta, C.T., M.L. Gazarini, F.H. Beraldo,
      F.P. Varotti, C. Lopes, R.P. Markus, T. Pozzan, and C.R. Garcia. 2000. Nat. Cell
      Biol. 2:466-468). Here we show that in Plasmodium falciparum melatonin induces an
      increase in cyclic AMP (cAMP) levels and cAMP-dependent protein kinase (PKA)
      activity (40 and 50%, respectively). When red blood cells infected with P.
      falciparum are treated with cAMP analogue adenosine 3',5'-cyclic monophosphate N6
      benzoyl/PKA activator (6-Bz-cAMP) there is an alteration of the parasite cell
      cycle. This effect appears to depend on activation of PKA (abolished by the PKA
      inhibitors adenosine 3',5'-cyclic monophosphorothioate/8 Bromo Rp isomer, PKI
      [cell permeable peptide], and H89). An unexpected cross talk was found to exist
      between the cAMP and the Ca(2+)-dependent signaling pathways. The increases in
      cAMP by melatonin are inhibited by blocker of phospholipase C U73122, and
      addition of 6-Bz-cAMP increases cytosolic Ca(2+) concentration, through PKA
      activation. These findings suggest that in Plasmodium a highly complex interplay
      exists between the Ca(2+) and cAMP signaling pathways, but also that the control
      of the parasite cell cycle by melatonin requires the activation of both second
      messenger controlled pathways.

PMID- 16103225
TI  - Sgk3 links growth factor signaling to maintenance of progenitor cells in the hair
      follicle.
AB  - Tyrosine kinase growth factor receptor signaling influences proliferation,
      survival, and apoptosis. Hair follicles undergo cycles of proliferation and
      apoptotic regression, offering an excellent paradigm to study how this transition
      is governed. Several factors are known to affect the hair cycle, but it remains a
      mystery whether Akt kinases that are downstream of growth factor signaling impact
      this equilibrium. We now show that an Akt relative, Sgk (serum and glucocorticoid
      responsive kinase) 3, plays a critical role in this process. Hair follicles of
      mice lacking Sgk3 fail to mature normally. Proliferation is reduced, apoptosis is
      increased, and follicles prematurely regress. Maintenance of the pool of
      transiently amplifying matrix cells is impaired. Intriguingly, loss of Sgk3
      resembles the gain of function of epidermal growth factor signaling. Using
      cultured primary keratinocytes, we find that Sgk3 functions by negatively
      regulating phosphatidylinositol 3 kinase signaling. Our results reveal a novel
      and important function for Sgk3 in controlling life and death in the hair
      follicle.

PMID- 16103226
TI  - An ECT2-centralspindlin complex regulates the localization and function of RhoA.
AB  - In anaphase, the spindle dictates the site of contractile ring assembly. Assembly
      and ingression of the contractile ring involves activation of myosin-II and actin
      polymerization, which are triggered by the GTPase RhoA. In many cells, the
      central spindle affects division plane positioning via unknown molecular
      mechanisms. Here, we dissect furrow formation in human cells and show that the
      RhoGEF ECT2 is required for cortical localization of RhoA and contractile ring
      assembly. ECT2 concentrates on the central spindle by binding to centralspindlin.
      Depletion of the centralspindlin component MKLP1 prevents central spindle
      localization of ECT2; however, RhoA, F-actin, and myosin still accumulate on the
      equatorial cell cortex. Depletion of the other centralspindlin component, CYK
      4/MgcRacGAP, prevents cortical accumulation of RhoA, F-actin, and myosin. CYK-4
      and ECT2 interact, and this interaction is cell cycle regulated via ECT2
      phosphorylation. Thus, central spindle localization of ECT2 assists division
      plane positioning and the CYK-4 subunit of centralspindlin acts upstream of RhoA
      to promote furrow assembly.

PMID- 16103227
TI  - Rho GTPase regulation of exocytosis in yeast is independent of GTP hydrolysis and
      polarization of the exocyst complex.
AB  - Rho GTPases are important regulators of polarity in eukaryotic cells. In yeast
      they are involved in regulating the docking and fusion of secretory vesicles with
      the cell surface. Our analysis of a Rho3 mutant that is unable to interact with
      the Exo70 subunit of the exocyst reveals a normal polarization of the exocyst
      complex as well as other polarity markers. We also find that there is no
      redundancy between the Rho3-Exo70 and Rho1-Sec3 pathways in the localization of
      the exocyst. This suggests that Rho3 and Cdc42 act to polarize exocytosis by
      activating the exocytic machinery at the membrane without the need to first
      recruit it to sites of polarized growth. Consistent with this model, we find that
      the ability of Rho3 and Cdc42 to hydrolyze GTP is not required for their role in
      secretion. Moreover, our analysis of the Sec3 subunit of the exocyst suggests
      that polarization of the exocyst may be a consequence rather than a cause of
      polarized exocytosis.

PMID- 16103228
TI  - An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the
      endocytic pathway.
AB  - Generation and turnover of phosphoinositides (PIs) must be coordinated in a
      spatial- and temporal-restricted manner. The small GTPase Rab5 interacts with two
      PI 3-kinases, Vps34 and PI3Kbeta, suggesting that it regulates the production of
      3-PIs at various stages of the early endocytic pathway. Here, we discovered that
      Rab5 also interacts directly with PI 5- and PI 4-phosphatases and stimulates
      their activity. Rab5 regulates the production of phosphatidylinositol 3-phosphate
      (PtdIns[3]P) through a dual mechanism, by directly phosphorylating
      phosphatidylinositol via Vps34 and by a hierarchical enzymatic cascade of
      phosphoinositide-3-kinasebeta (PI3Kbeta), PI 5-, and PI 4-phosphatases. The
      functional importance of such an enzymatic pathway is demonstrated by the
      inhibition of transferrin uptake upon silencing of PI 4-phosphatase and studies
      in weeble mutant mice, where deficiency of PI 4-phosphatase causes an increase of
      PtdIns(3,4)P2 and a reduction in PtdIns(3)P. Activation of PI 3-kinase at the
      plasma membrane is accompanied by the recruitment of Rab5, PI 4-, and PI 5
      phosphatases to the cell cortex. Our data provide the first evidence for a dual
      role of a Rab GTPase in regulating both generation and turnover of PIs via PI
      kinases and phosphatases to coordinate signaling functions with organelle
      homeostasis.

PMID- 16103229
TI  - Reaching out for signals: filopodia sense EGF and respond by directed retrograde
      transport of activated receptors.
AB  - ErbB1 receptors situated on cellular filopodia undergo systematic retrograde
      transport after binding of the epidermal growth factor (EGF) and activation of
      the receptor tyrosine kinase. Specific inhibitors of the erbB1 receptor tyrosine
      kinase as well as cytochalasin D, a disruptor of the actin cytoskeleton, abolish
      transport but not free diffusion of the receptor-ligand complex. Diffusion
      constants and transport rates were determined with single molecule sensitivity by
      tracking receptors labeled with EGF conjugated to fluorescent quantum dots.
      Retrograde transport precedes receptor endocytosis, which occurs at the base of
      the filopodia. Initiation of transport requires the interaction and concerted
      activation of at least two liganded receptors and proceeds at a constant rate
      mediated by association with actin. These findings suggest a mechanism by which
      filopodia detect the presence and concentration of effector molecules far from
      the cell body and mediate cellular responses via directed transport of activated
      receptors.

PMID- 16103230
TI  - Intraflagellar transport (IFT) during assembly and disassembly of Chlamydomonas
      flagella.
AB  - Intraflagellar transport (IFT) of particles along flagellar microtubules is
      required for the assembly and maintenance of eukaryotic flagella and cilia. In
      Chlamydomonas, anterograde and retrograde particles viewed by light microscopy
      average 0.12-microm and 0.06-microm diameter, respectively. Examination of IFT
      particle structure in growing flagella by electron microscopy revealed similar
      size aggregates composed of small particles linked to each other and to the
      membrane and microtubules. To determine the relationship between the number of
      particles and flagellar length, the rate and frequency of IFT particle movement
      was measured in nongrowing, growing, and shortening flagella. In all flagella,
      anterograde and retrograde IFT averaged 1.9 microm/s and 2.7 microm/s,
      respectively, but retrograde IFT was significantly slower in flagella shorter
      than 4 mum. The number of flagellar IFT particles was not fixed, but depended on
      flagellar length. Pauses in IFT particle entry into flagella suggest the presence
      of a periodic "gate" that permits up to 4 particles/s to enter a flagellum.

PMID- 16103231
TI  - Process outgrowth in oligodendrocytes is mediated by CNP, a novel microtubule
      assembly myelin protein.
AB  - Oligodendrocytes (OLs) extend arborized processes that are supported by
      microtubules (MTs) and microfilaments. Little is known about proteins that
      modulate and interact with the cytoskeleton during myelination. Several lines of
      evidence suggest a role for 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in
      mediating process formation in OLs. In this study, we report that tubulin is a
      major CNP-interacting protein. In vitro, CNP binds preferentially to tubulin
      heterodimers compared with MTs and induces MT assembly by copolymerizing with
      tubulin. CNP overexpression induces dramatic morphology changes in both glial and
      nonglial cells, resulting in MT and F-actin reorganization and formation of
      branched processes. These morphological effects are attributed to CNP MT assembly
      activity; branched process formation is either substantially reduced or abolished
      with the expression of loss-of-function mutants. Accordingly, cultured OLs from
      CNP-deficient mice extend smaller outgrowths with less arborized processes. We
      propose that CNP is an important component of the cytoskeletal machinery that
      directs process outgrowth in OLs.

PMID- 16103232
TI  - beta-Catenin controls cell sorting at the notochord-somite boundary independently
      of cadherin-mediated adhesion.
AB  - In Xenopus laevis, patterning of the trunk mesoderm into the dorsal notochord and
      lateral somites depends on differential regulation of Wnt-beta-catenin signaling.
      To study the cellular requirements for the physical separation of these tissues,
      we manipulated beta-catenin activity in individual cells that were scattered
      within the trunk mesoderm. We found that high activity led to efficient cell
      sorting from the notochord to the somites, whereas reduced activity led to
      sorting in the opposite direction. Analysis of individual cells overexpressing
      beta-catenin revealed that these cells were unable to establish stable contacts
      with notochord cells but could freely cross the boundary to integrate within the
      somitic tissue. Interference with cadherin-mediated adhesion disrupted tissue
      architecture, but it did not affect sorting and boundary formation. Based on
      these results, we propose that the boundary itself is the result of cell
      autonomous changes in contact behavior that do not rely on differences in
      absolute levels of adhesion.

PMID- 16103233
TI  - Anemia and change in hemoglobin over time related to mortality and morbidity in
      patients with chronic heart failure: results from Val-HeFT.
AB  - BACKGROUND: Anemia is known to be a prognostic marker for patients with heart
      failure. However, little is known about the prognostic value of changes in
      hemoglobin (Hgb) over time or about the causes of anemia. METHODS AND RESULTS:
      Retrospective analysis of Valsartan Heart Failure Trial data indicated that the
      quartile of patients with the biggest average decrease in Hgb over 12 months
      (from 14.2 to 12.6 g/dL) had significantly (P< or =0.01) increased risk of
      subsequent hospitalization (hazard ratio [HR], 1.47), morbid events (HR, 1.41),
      and death (HR, 1.6) compared with the quartile that exhibited little change in
      Hgb over 12 months (from 13.7 to 13.8 g/dL). Increasing Hgb was significantly
      associated with lower mortality in patients with (HR, 0.78) and without (HR,
      0.79) anemia at baseline. Anemia at baseline and the changes in Hgb were
      independently associated with serum albumin, blood pressure, glomerular
      filtration rate, B-type natriuretic peptide, and C-reactive protein. Lack of
      anemia at baseline and increases in Hgb over 12 months were not associated with
      smaller left ventricular diameters or higher ejection fractions. CONCLUSIONS:
      Changes in Hgb over 12 months were inversely associated with subsequent risk of
      mortality and morbidity, independently of the effects of baseline anemia and
      other important predictors. Several factors were independently related to anemia
      at baseline and changes in Hgb, suggesting multiple causes of anemia in patients
      with heart failure. These findings raise important questions about the optimal
      level of Hgb in patients with moderate to severe heart failure and how to achieve
      them.

PMID- 16103234
TI  - Reversal of cardiomyopathy in patients with repetitive monomorphic ventricular
      ectopy originating from the right ventricular outflow tract.
AB  - BACKGROUND: Tachycardia-induced cardiomyopathy caused by ventricular tachycardia
      is a well-defined clinical entity. Less well appreciated is whether simple
      ventricular ectopy can result in cardiomyopathy. We sought to examine a potential
      causal relationship between repetitive monomorphic ventricular ectopy originating
      from the right ventricular outflow tract and cardiomyopathy and the role of
      ablation in reversing this process. METHODS AND RESULTS: The study consisted of
      27 patients (11 men; age, 47+/-15 years) with repetitive monomorphic ventricular
      ectopy, including 8 patients (30%) with depressed ventricular function (ejection
      fraction < or =45%). All patients underwent assessment of cardiac structure and
      function. The burden of ectopy was quantified through 24-hour Holter monitoring.
      Patients then underwent ablation guided by 3D mapping. After ablation, patients
      underwent repeated Holter monitoring and reassessment of cardiac function.
      Patients with depressed ventricular function were more likely to be older than
      patients with normal function (58+/-14 versus 42+/-18 years; P=0.013). However,
      the burden of ventricular ectopy was similar in patients with (17,859+/-13,488
      ectopic beats per 24 hours) and without (17,541+/-11,479 ectopic beats per 24
      hours; P=0.800) preserved ventricular function. Successful ablation was performed
      in 23 patients (85%), including 7 of 8 patients with depressed ventricular
      function. In this latter group, ventricular function improved in all patients
      (from 39+/-6% to 62+/-6%; P=0.017). CONCLUSIONS: Repetitive monomorphic
      ventricular ectopy (in the absence of sustained ventricular tachycardia)
      originating from the right ventricular outflow tract is an underappreciated cause
      of unexplained cardiomyopathy. Successful ablation of the focal source of
      ventricular ectopy results in normalization of left ventricular function.
      Patients with ectopy-induced cardiomyopathy are significantly older than patients
      with preserved ventricular function, which suggests either that older patients
      are more susceptible to the development of a cardiomyopathy or that the
      cardiomyopathy has had a longer period of time in which to evolve.

PMID- 16103235
TI  - Platelet adhesion via glycoprotein IIb integrin is critical for atheroprogression
      and focal cerebral ischemia: an in vivo study in mice lacking glycoprotein IIb.
AB  - BACKGROUND: The platelet glycoprotein (GP) IIb/IIIa integrin binds to fibrinogen
      and thereby mediates platelet aggregation. Here, we addressed the role of GP IIb
      for platelet adhesion and determined the relevance of platelet GP IIb for the
      processes of atherosclerosis and cerebral ischemia-reperfusion (I/R) injury.
      METHODS AND RESULTS: GP IIb(-/-) mice were generated and bred with ApoE(-/-)
      animals to create GP IIb(-/-)ApoE(-/-) mice. Platelet adhesion to the
      mechanically injured or atherosclerotic vessel wall was monitored by in vivo
      video fluorescence microscopy. In the presence of GP IIb, vascular injury and
      early atherosclerosis induced platelet adhesion in the carotid artery (CA). In
      contrast, platelet adhesion was significantly reduced in the absence of GP IIb
      integrin (P<0.05). To address the contribution of platelet GP IIb to
      atheroprogression, we determined atherosclerotic lesion formation in the CA and
      aortic arch (AA) of GP IIb(+/+)ApoE(-/-) or GP IIb(-/-)ApoE(-/-) mice.
      Interestingly, the absence of GP IIb attenuated lesion formation in CA and AA,
      indicating that platelets, via GP IIb, contribute substantially to
      atherosclerosis. Next, we assessed the implication of GP IIb for cerebral I/R
      injury. We observed that after occlusion of the middle cerebral artery, the
      cerebral infarct size was drastically reduced in mice lacking GP IIb compared
      with wild-types. CONCLUSIONS: These findings show for the first time in vivo that
      GP IIb not only mediates platelet aggregation but also triggers platelet adhesion
      to exposed extracellular matrices and dysfunctional endothelial cells. In a
      process strictly involving GP IIb, platelets, which are among the first blood
      cells to arrive at the scene of endothelial dysfunction, contribute essentially
      to atherosclerosis and cerebral I/R injury.

PMID- 16103236
TI  - Systemic endothelial dysfunction in adults with cyanotic congenital heart
      disease.
AB  - BACKGROUND: Secondary erythrocytosis results in increased shear stress in
      cyanotic congenital heart disease (CCHD), which may modify the balance between
      vasodilators and vasoconstrictors and affect systemic endothelial function.
      Because no data are available on systemic vasomotion, systemic endothelial
      function and nitric oxide (NO) availability were investigated in CCHD patients.
      METHODS AND RESULTS: Responses to arterial endothelium-dependent (acetylcholine
      [Ach]) and -independent (sodium nitroprusside [SNP]) vasodilation, NO synthase
      blockade (NG-monomethyl-L-arginine [L-NMMA]), endothelin-1 (ET-1), and ET-1
      receptor blockade by BQ-123 in 11 CCHD patients (O2 saturation <90%; mean+/-SD,
      79+/-1%; mean+/-SD age, 39+/-2 years) were compared with those in 10 age-matched
      healthy referents by using forearm venous occlusion plethysmography. Resting
      forearm blood flow (FBF) was lower in CCHD patients than in referents (2.4+/-0.2
      versus 3.5+/-0.4 mL.min(-1).100 mL(-1) of forearm volume [FAV], P<0.05). Although
      the response to SNP was similar in both groups (CCHD, 2.0+/-0.3 to 8.3+/-1.0;
      referents, 3.6+/-0.7 to 11.9+/-1.2 mL.min(-1).100 mL(-1) of FAV; P>0.1), the
      response to Ach was markedly reduced in CCHD (maximal increase in FBF, 2.8+/-0.8
      versus 37.5+/-4.4 mL.min(-1).100 mL(-1) of FAV; P<0.0001). l-NMMA was less
      effective in CCHD (decrease in FBF, 25+/-6% versus 40+/-4%; P<0.05). ET-1 caused
      less vasoconstriction in the CCHD group (-25+/-9% versus -51+/-7%, P<0.05), but
      the response to BQ-123 was similar in both groups (32+/-9% versus 27+/-9%).
      CONCLUSIONS: Systemic endothelial dysfunction is evident in CCHD patients as
      shown by strikingly reduced endothelial vasodilation to Ach. The response to
      exogenous ET-1 is reduced, possibly because of elevated endogenous ET-1 levels,
      but the effects of endogenous ET-1 on arterial tone are not enhanced, as
      indicated by the similar response to ET-1 blockade.

PMID- 16103237
TI  - Vascular smooth muscle overexpression of G protein-coupled receptor kinase 5
      elevates blood pressure, which segregates with sex and is dependent on Gi
      mediated signaling.
AB  - BACKGROUND: Essential hypertension involves an increase in sympathetic nervous
      system activity and an associated decrease in beta-adrenergic receptor (AR)
      mediated dilation. In addition, increased levels of G protein-coupled receptor
      (GPCR) kinases (GRKs), which regulate GPCR signaling, are associated with
      increased blood pressure (BP). METHODS AND RESULTS: We generated transgenic mice
      with approximately 2-fold vascular smooth muscle (VSM)-specific overexpression of
      GRK5 to recapitulate a selective aspect of hypertension and understand the impact
      on GPCR regulation of BP. VSM-GRK5 mice were hypertensive, with a 25% to 35%
      increase in BP, whereas there was no concomitant cardiac or VSM hypertrophy. BP
      elevations were segregated with sex, with male mice having higher levels than
      female mice, and ovariectomy did not alter this phenotype. BP was restored to
      control values with pertussis toxin Gi-signaling inhibition or chronic beta1AR
      inhibition after 7 days of CGP20712A, whereas the beta2AR antagonist ICI 118,551
      was ineffective. Alpha1AR response was not altered, nor was betaAR-mediated
      dilation in male blood vessels, whereas norepinephrine sensitivity was increased.
      In contrast, female VSM-GRK5 blood vessels have diminished betaAR-mediated
      dilation and enhanced sensitivity to angiotensin II (Ang II). CONCLUSIONS: Our
      data suggest that in both male and female mice, VSM-specific overexpression of
      GRK5 elevates BP mediated by Gi and, at least in part, by beta1AR in males and
      Ang II receptors in females. Understanding mechanisms underlying an increase in
      VSM-GRK5 may have a profound influence on the use and development of
      antihypertensive therapeutics.

PMID- 16103238
TI  - Volume-outcome relationships for percutaneous coronary interventions in the stent
      era.
AB  - BACKGROUND: Most studies that are the basis of recommended volume thresholds for
      percutaneous coronary interventions (PCIs) predate the routine use of stent
      placement. METHODS AND RESULTS: Data from New York's Percutaneous Coronary
      Interventions Reporting System in 1998 to 2000 (n=107 713) were used to examine
      the impact of annual hospital volume and annual operator volume on in-hospital
      mortality, same-day coronary artery bypass graft (CABG) surgery, and same-stay
      CABG surgery after adjustment for differences in patients' severity of illness.
      For a hospital-volume threshold of 400, the odds ratios for low-volume hospitals
      versus high-volume hospitals were 1.98 (95% CI, 1.17, 3.35) for in-hospital
      mortality, 2.07 (95% CI, 1.36, 3.15) for same-day CABG surgery, and 1.51 (95% CI,
      1.03, 2.21) for same-stay CABG surgery. For an operator-volume threshold of 75,
      the odds ratios for low-volume versus high-volume operators were 1.65 (95% CI,
      1.05, 2.60) for same-day CABG surgery and 1.55 (95% CI, 1.10, 2.18) for same-stay
      CABG surgery. Operator volume was not significantly associated with mortality.
      Also, for hospital volumes below 400 and operator volumes below 75, the
      respective odds of mortality, same-day CABG surgery, and same-stay CABG surgery
      were 5.92, 4.02, and 3.92 times the odds for hospital volumes of 400 or higher
      and operator volumes of 75 or higher. CONCLUSIONS: Higher-volume operators and
      hospitals continue to experience lower risk-adjusted PCI outcome rates.

PMID- 16103239
TI  - Percutaneous pulmonary valve implantation in humans: results in 59 consecutive
      patients.
AB  - BACKGROUND: Right ventricular outflow tract (RVOT) reconstruction with valved
      conduits in infancy and childhood leads to reintervention for pulmonary
      regurgitation and stenosis in later life. METHODS AND RESULTS: Patients with
      pulmonary regurgitation with or without stenosis after repair of congenital heart
      disease had percutaneous pulmonary valve implantation (PPVI). Mortality,
      hemodynamic improvement, freedom from explantation, and subjective and objective
      changes in exercise tolerance were end points. PPVI was performed successfully in
      58 patients, 32 male, with a median age of 16 years and median weight of 56 kg.
      The majority had a variant of tetralogy of Fallot (n=36), or transposition of the
      great arteries, ventricular septal defect with pulmonary stenosis (n=8). The
      right ventricular (RV) pressure (64.4+/-17.2 to 50.4+/-14 mm Hg, P<0.001), RVOT
      gradient (33+/-24.6 to 19.5+/-15.3, P<0.001), and pulmonary regurgitation (PR)
      (grade 2 of greater before, none greater than grade 2 after, P<0.001) decreased
      significantly after PPVI. MRI showed significant reduction in PR fraction (21+/
      13% versus 3+/-4%, P<0.001) and in RV end-diastolic volume (EDV) (94+/-28 versus
      82+/-24 mL.beat(-1).m(-2), P<0.001) and a significant increase in left
      ventricular EDV (64+/-12 versus 71+/-13 mL.beat(-1).m(-2), P=0.005) and effective
      RV stroke volume (37+/-7 versus 42+/-9 mL.beat(-1).m(-2), P=0.006) in 28 patients
      (age 19+/-8 years). A further 16 subjects, on metabolic exercise testing, showed
      significant improvement in VO2max (26+/-7 versus 29+/-6 mL.kg(-1).min(-1),
      P<0.001). There was no mortality. CONCLUSIONS: PPVI is feasible at low risk, with
      quantifiable improvement in MRI-defined ventricular parameters and pulmonary
      regurgitation, and results in subjective and objective improvement in exercise
      capacity.

PMID- 16103240
TI  - Increased cardiac expression of tissue inhibitor of metalloproteinase-1 and
      tissue inhibitor of metalloproteinase-2 is related to cardiac fibrosis and
      dysfunction in the chronic pressure-overloaded human heart.
AB  - BACKGROUND: Alterations in the balance of matrix metalloproteinases (MMPs) and
      their specific tissue inhibitors (TIMPs) are involved in left ventricular (LV)
      remodeling. Whether their expression is related to interstitial fibrosis or LV
      dysfunction in patients with chronic pressure overload-induced LV hypertrophy,
      however, is unknown. METHODS AND RESULTS: Therefore, cardiac biopsies were taken
      in 36 patients with isolated aortic stenosis (AS) and in 29 control patients
      without LV hypertrophy. Microarray analysis revealed significantly increased mRNA
      expression of collagen types I, III, and IV and transcripts involved in collagen
      synthesis, including procollagen endopeptidase and lysine and proline
      hydroxylases, in AS compared with control patients. Collagen deposition was
      greater in AS than in control patients and was most pronounced in AS patients
      with severe diastolic dysfunction. Cardiac mRNA expression of TIMP-1 and TIMP-2
      was significantly increased in AS compared with control patients (mRNA transcript
      levels normalized to GAPDH: TIMP-1, 0.67+/-0.1 in AS versus 0.37+/-0.08 in
      control patients; TIMP-2, 9.5+/-2.6 in AS versus 1.6+/-0.4 in control patients;
      P<0.05 for both) but did not differ significantly for MMP-1, -2, or -9. Cardiac
      TIMP-1 and -2 transcripts were significantly related to the degree of
      interstitial fibrosis and proportional to diastolic dysfunction in AS patients.
      CONCLUSIONS: Cardiac expression of TIMP-1 and TIMP-2 is significantly increased
      in chronic pressure-overloaded human hearts compared with controls and is related
      to the degree of interstitial fibrosis.

PMID- 16103241
TI  - Detection of coronary stenoses at rest with myocardial contrast echocardiography.
AB  - BACKGROUND: We hypothesized that autoregulatory changes in arteriolar blood
      volume (aBV) that develop distal to a stenosis can be measured with myocardial
      contrast echocardiography, allowing coronary stenosis detection at rest without
      recourse to stress. METHODS AND RESULTS: Patients with varying degrees of
      coronary artery stenosis on quantitative angiography underwent high-mechanical
      index myocardial contrast echocardiography at 15 Hz to allow measurement of
      phasic changes in aBV in large intramyocardial vessels using either Definity
      (group 1; n=22) or Imagent (group 2; n=22). Progressive increases in the
      BACKGROUND: <0.001) and group 2 (0.10+/-0.05, 0.27+/-0.18, 0.39+/-0.28, and
      0.74+/-0.37; P<0.0001) patients. A systolic/diastolic aBV signal ratio of >0.34
      provided a sensitivity and specificity of 80% and 71%, respectively, for the
      detection of >75% coronary stenosis in group 1 patients, whereas a ratio of >0.43
      provided a sensitivity and specificity of 89% and 74%, respectively, for the
      detection of >75% stenosis in group 2 patients. CONCLUSIONS: Both the presence
      and severity of a physiologically significant coronary stenosis can be detected
      at rest by measuring the increase in aBV on myocardial contrast echocardiography
      that occurs distally to the stenosis without recourse to any form of stress.

PMID- 16103242
TI  - Volumetric quantification of global and regional left ventricular function from
      real-time three-dimensional echocardiographic images.
AB  - BACKGROUND: Real-time 3D echocardiographic (RT3DE) data sets contain dynamic
      volumetric information on cardiac function. However, quantification of left
      ventricular (LV) function from 3D echocardiographic data is performed on cut
      planes extracted from the 3D data sets and thus does not fully exploit the
      volumetric information. Accordingly, we developed a volumetric analysis technique
      aimed at quantification of global and regional LV function. METHODS AND RESULTS:
      RT3DE images obtained in 30 patients (Philips 7500) were analyzed by use of
      custom software based on the level-set approach for semiautomated detection of LV
      endocardial surface throughout the cardiac cycle, from which global and regional
      LV volume (LVV)-time and wall motion (WM)-time curves were obtained. The study
      design included 3 protocols. In protocol 1, time curves obtained in 16 patients
      were compared point-by-point with MRI data (linear regression and Bland-Altman
      analyses). Global LVV correlated highly with MRI (r=0.98; y=0.99x+2.3) with
      minimal bias (1.4 mL) and narrow limits of agreement (+/-20 mL). WM correlated
      highly only in basal and midventricular segments (r=0.88; y=0.85x+0.7). In
      protocol 2, we tested the ability of this technique to differentiate populations
      with known differences in LV function by studying 9 patients with dilated
      cardiomyopathy and 9 normal subjects. All calculated indices of global and
      regional systolic and diastolic LV function were significantly different between
      the groups. In protocol 3, we tested the feasibility of automated detection of
      regional WM abnormalities in 11 patients. In each segment, abnormality was
      detected when regional shortening fraction was below a threshold obtained in
      normal subjects. The automated detection agreed with expert interpretation of 2D
      WM in 86% of segments. CONCLUSIONS: Volumetric analysis of RT3DE data is
      clinically feasible and allows fast, semiautomated, dynamic measurement of LVV
      and automated detection of regional WM abnormalities.

PMID- 16103243
TI  - Transplantation of mesenchymal stem cells improves cardiac function in a rat
      model of dilated cardiomyopathy.
AB  - BACKGROUND: Pluripotent mesenchymal stem cells (MSCs) differentiate into a
      variety of cells, including cardiomyocytes and vascular endothelial cells.
      However, little information is available about the therapeutic potency of MSC
      transplantation in cases of dilated cardiomyopathy (DCM), an important cause of
      heart failure. METHODS AND RESULTS: We investigated whether transplanted MSCs
      induce myogenesis and angiogenesis and improve cardiac function in a rat model of
      DCM. MSCs were isolated from bone marrow aspirates of isogenic adult rats and
      expanded ex vivo. Cultured MSCs secreted large amounts of the angiogenic,
      antiapoptotic, and mitogenic factors vascular endothelial growth factor,
      hepatocyte growth factor, adrenomedullin, and insulin-like growth factor-1. Five
      weeks after immunization, MSCs or vehicle was injected into the myocardium. Some
      engrafted MSCs were positive for the cardiac markers desmin, cardiac troponin T,
      and connexin-43, whereas others formed vascular structures and were positive for
      von Willebrand factor or smooth muscle actin. Compared with vehicle injection,
      MSC transplantation significantly increased capillary density and decreased the
      collagen volume fraction in the myocardium, resulting in decreased left
      ventricular end-diastolic pressure (11+/-1 versus 16+/-1 mm Hg, P<0.05) and
      increased left ventricular maximum dP/dt (6767+/-323 versus 5138+/-280 mm Hg/s,
      P<0.05). CONCLUSIONS: MSC transplantation improved cardiac function in a rat
      model of DCM, possibly through induction of myogenesis and angiogenesis, as well
      as by inhibition of myocardial fibrosis. The beneficial effects of MSCs might be
      mediated not only by their differentiation into cardiomyocytes and vascular cells
      but also by their ability to supply large amounts of angiogenic, antiapoptotic,
      and mitogenic factors.

PMID- 16103244
TI  - Should aspirin be discontinued before coronary artery bypass surgery?

PMID- 16103245
TI  - Images in cardiovascular medicine. Prinzmetal angina in an adolescent: adjunctive
      role of tissue synchronization imaging.

PMID- 16103246
TI  - Images in cardiovascular medicine. Visualization of regional left ventricular
      mechanical delay by tissue synchronization imaging in heart failure patients with
      wide and narrow QRS complexes undergoing cardiac resynchronization therapy.

PMID- 16103247
TI  - Images in cardiovascular medicine. Adult patient with isolated noncompaction of
      ventricular myocardium.

PMID- 16103248
TI  - Letter regarding article by Nallamothu et al, "Times to treatment in transfer
      patients undergoing primary percutaneous coronary intervention in the United
      states".

PMID- 16103249
TI  - The transition from hypertrophy to failure: how certain are we?

PMID- 16103250
TI  - Gene therapy to treat aortic aneurysms: right goal, wrong strategy.

PMID- 16103251
TI  - To the heart of the matter: coxibs, smoking, and cardiovascular risk.

PMID- 16103252
TI  - Incidence and clinical relevance of slow ventricular tachycardia in implantable
      cardioverter-defibrillator recipients: an international multicenter prospective
      study.
AB  - BACKGROUND: This study aims to assess the incidence and clinical relevance of
      slow ventricular tachycardia (VT) and the effectiveness and/or deleterious
      effects of antitachycardia pacing in slow VT in implantable cardioverter
      defibrillator recipients. METHODS AND RESULTS: This multicenter prospective
      randomized study included 374 patients (326 men) without prior history of slow VT
      (<148 bpm) implanted with a dual-chamber implantable cardioverter-defibrillator.
      Patients had a 3-zone detection configuration: a slow VT zone (101 to 148 bpm), a
      conventional VT zone (>148 bpm), and a ventricular fibrillation zone. Patients
      were randomized to a treatment group (n=183) with therapy activated in the slow
      VT zone or a monitoring group (n=191) with no therapy in the slow VT zone. During
      follow-up (11 months), 449 slow VTs occurred in 114 patients (30.5% slow VT
      incidence); 181 VTs (54 patients) occurred in the monitoring group; 3 were
      readmitted to the hospital; and lightheadedness and palpitations occurred in 4
      and 250 (60 patients) in the treatment group treated by antitachycardia pacing
      (89.8% success rate) and shock delivery (n=2). There were 10 crossovers from the
      monitoring to treatment group and 3 crossovers from the treatment to monitoring
      group (P=0.09). Quality of life scores were not different between groups.
      CONCLUSIONS: Slow VT incidence (<150 bpm) is high (30%) in implantable
      cardioverter-defibrillator recipients without prior history of slow VT, has
      limited clinical relevance, and is efficiently and safely terminated by
      antitachycardia pacing.

PMID- 16103253
TI  - Left ventricular concentric remodeling is associated with decreased global and
      regional systolic function: the Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: The transition from compensatory concentric remodeling to myocardial
      failure is not completely understood in humans. To investigate determinants of
      incipient myocardial dysfunction, we examined the association between concentric
      remodeling and regional LV function in asymptomatic participants of the Multi
      Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: Myocardial tagged
      MRI was performed. Regional myocardial function expressed as peak systolic
      midwall circumferential strain (Ecc) was analyzed in 441 consecutive studies by
      HARP (Harmonic Phase) tool. Peak Ecc was correlated with the extent of concentric
      remodeling determined by the ratio of left ventricular mass to end-diastolic
      volume (M/V ratio). In men, a gradual decline in peak global Ecc was seen with
      increasing M/V ratio (test for trend, P<0.001). Among women, however, Ecc tended
      to be lower only in the fifth compared with the first quintile of M/V ratio
      (P=0.1). The association of lower Ecc with increasing M/V ratio was regionally
      heterogeneous but was particularly prominent in the LAD region in men (test for
      trend, P<0.001) and in women (test for trend, P=0.02). In the right coronary and
      left circumflex artery territories, these associations were less marked in both
      genders. CONCLUSIONS: In this cross-sectional study of asymptomatic individuals,
      concentric left ventricular remodeling was related to decreased regional systolic
      function. The reduction in regional function, which was more pronounced in the
      left anterior descending coronary artery territory, may reflect the local
      transition from compensatory remodeling to myocardial dysfunction.

PMID- 16103254
TI  - Distal protection improved reperfusion and reduced left ventricular dysfunction
      in patients with acute myocardial infarction who had angioscopically defined
      ruptured plaque.
AB  - BACKGROUND: Distal protection, in the Saphenous Vein Graft Angioplasty Free of
      Emboli (SAFER) trial, is demonstrated to prevent distal embolism in the
      percutaneous coronary intervention of saphenous vein graft. However, in the
      Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberated Debris
      (EMERALD) trial, it was not effective in the percutaneous coronary intervention
      of native coronary arteries in patients with acute myocardial infarction (AMI).
      We hypothesized that its effectiveness would be determined by lesion
      characteristics. Therefore, we classified the type of culprit lesion by
      angioscopy and examined its influence on the effectiveness of distal protection,
      comparing patients with AMI treated with and without distal protection. METHODS
      AND RESULTS: Consecutive patients with AMI treated without distal protection
      (n=110) from July 2000 to July 2002 and those treated with distal protection
      (n=81) from July 2002 to July 2004 were included. Patients in each group were
      subdivided according to whether or not they had angioscopically defined ruptured
      plaque at culprit lesion. Among those groups, incidence of no-reflow phenomenon,
      ST-segment resolution, myocardial blush grade, and left ventricular ejection
      fraction at 6 months were compared. Aspirated samples by distal protection were
      semiquantitatively and histologically analyzed and compared between patients with
      and without ruptured plaque. No-reflow phenomenon was most frequently (P<0.05)
      observed in patients with ruptured plaque treated without distal protection. ST
      segment resolution (68+/-15% versus 40+/-21%, P<0.001), myocardial blush grade
      (2.6+/-0.5 versus 1.8+/-0.3, P<0.001), and left ventricular ejection fraction
      (47.2+/-6.7% versus 41.0+/-9.7%, P<0.01) were improved by distal protection among
      patients with ruptured plaque but not among patients without ruptured plaque.
      Aspirated samples >1 mm were detected more frequently (97.3% versus 78.5%,
      P<0.05) in patients with ruptured plaque than those without ruptured plaque.
      Histologically, aspirated samples contained plaque debris (95.3% versus 31.1%,
      P<0.05) more frequently in patients with ruptured plaque than in those without
      ruptured plaque. CONCLUSIONS: Distal protection reduced microcirculation damage
      and left ventricular dysfunction in patients with AMI who had angioscopically
      defined ruptured plaque. Distal embolization of plaque debris was detected more
      frequently in patients with ruptured plaque. These results suggest that
      microcirculation damage and left ventricular dysfunction are increased mainly by
      distal embolization of plaque debris rather than of thrombus.

PMID- 16103255
TI  - Overexpression of transforming growth factor-beta1 stabilizes already-formed
      aortic aneurysms: a first approach to induction of functional healing by
      endovascular gene therapy.
AB  - BACKGROUND: The cell response to transforming growth factor-beta1 (TGF-beta1), a
      multipotent cytokine with healing potential, varies according to tissue context.
      We have evaluated the ability of TGF-beta1 overexpression by endovascular gene
      therapy to stabilize abdominal aortic aneurysms (AAAs) already injured by
      inflammation and proteolysis. METHODS AND RESULTS: Active TGF-beta1
      overexpression was obtained in already-developed experimental AAAs in rats after
      endovascular delivery of an adenoviral construct encoding for a mutated form of
      active simian TGF-beta1 and in an explant model using human atherosclerotic AAA
      fragments incubated with recombinant active TGF-beta1. Transient exogenous TGF
      beta1 overexpression by endovascular gene delivery was followed by induction of
      endogenous rat TGF-beta1. Overexpression of active TGF-beta1 in experimental AAAs
      was associated with diameter stabilization, preservation of medial elastin,
      decreased infiltration of monocyte-macrophages and T lymphocytes, and a decrease
      in matrix metalloproteinase-2 and -9, which was also observed in the explant
      model, in both thrombus and wall. In parallel with downregulation of the
      destructive process, active TGF-beta1 overexpression triggered endoluminal
      reconstruction, replacing the thrombus by a vascular smooth muscle cell-,
      collagen-, and elastin-rich intima. CONCLUSIONS: Local TGF-beta1 self-induction
      after transient exogenous overexpression reprograms dilated aortas altered by
      inflammation and proteolysis and restores their ability to withstand arterial
      pressure without further dilation. This first demonstration of stabilization of
      expanding AAAs by delivery of a single multipotent self-promoting gene supports
      the view that endovascular gene therapy should be considered for treatment of
      aneurysms.

PMID- 16103256
TI  - Blockade of interleukin-12 function by protein vaccination attenuates
      atherosclerosis.
AB  - BACKGROUND: Interleukin-12 (IL-12) has been identified as a key inducer of a type
      1 T-helper cell cytokine pattern, which is thought to contribute to the
      development of atherosclerosis. We sought to study the role of IL-12 in
      atherosclerosis by inhibition of IL-12 using a newly developed vaccination
      technique that fully blocks the action of IL-12. METHODS AND RESULTS: LDL
      receptor-deficient (LDLr(-/-)) mice were vaccinated against IL-12 by 5
      intramuscular injections of IL-12-PADRE complex in combination with adjuvant oil
      in-water emulsion (low dose)/MPL/QS21 every 2 weeks. Two weeks thereafter,
      atherogenesis was initiated in the carotid artery by perivascular placement of
      silicone elastomer collars. IL-12 vaccination resulted in the induction of anti
      IL-12 antibodies that functionally blocked the action of IL-12 as determined in
      an IL-12 bioassay. Blockade of IL-12 by vaccination of LDLr(-/-) mice resulted in
      significantly reduced (68.5%; P<0.01) atherogenesis compared with control mice
      without a change in serum cholesterol levels. IL-12 vaccination also resulted in
      a significant decrease in intima/media ratios (66.7%; P<0.01) and in the degree
      of stenosis (57.8%; P<0.01). On IL-12 vaccination, smooth muscle cell and
      collagen content in the neointima increased 2.8-fold (P<0.01) and 4.2-fold
      (P<0.01), respectively. CONCLUSIONS: Functional blockade of endogenous IL-12 by
      vaccination resulted in a significant 68.5% reduction in atherogenesis in LDLr(-/
      ) mice. Vaccination against IL-12 also improved plaque stability, from which we
      conclude that the blockade of IL-12 by vaccination may be considered a promising
      new strategy in the treatment of atherosclerosis.

PMID- 16103257
TI  - Patent foramen ovale and stroke.

PMID- 16103258
TI  - Selective cyclooxygenase-2 inhibitors development in cardiovascular medicine.

PMID- 16103259
TI  - Novel mass spectrometric methods for evaluation of plasma angiotensin converting
      enzyme 1 and renin activity.
AB  - This article demonstrates the applicability of quantitative proteomics to assays
      of proteolytic enzyme activity. A novel assay was developed for measurement of
      renin and angiotensin-converting enzyme (ACE) activity in plasma. The method was
      validated in animal models associated with alterations of the renin angiotensin
      system (RAS). Using surface-enhanced laser desorption/ionization time of flight
      mass spectrometry (SELDI-TOF-MS) with a ProteinChip Array technology, plasma
      renin and ACE1 could be measured in <0.5 microL of plasma. Plasma is incubated
      with peptide substrates for renin and ACE, tetradecapeptide (TDP), and
      angiotensin I (Ang I), respectively. The reactions mixtures are spotted onto the
      ProteinChip WCX2 and detected using SELDI-TOF-MS. Peak height or area under curve
      for TDP, Ang I, and angiotensin II (Ang II) peaks are measured. There was a
      linear relationship between disappearance of substrate and appearance of products
      for both renin and ACE (R2=0.95 to 0.98). ACE1 activity was blocked with
      chelating agents (EDTA and 1,10 phenanthrolene), indicating action of a
      metalloprotease. The ACE1 inhibitor, captopril, selectively blocked ACE1. Renin
      activity was specifically blocked with renin inhibitor and was not affected by
      phenanthrolene or captopril. Animal models tested were Ang AT1a receptor
      deficient and streptozotocin (STZ) diabetic mice. Plasma renin activity was
      increased >2-fold in AT1a(-/-) as compared with AT1a(+/+). In STZ diabetic mice,
      ACE1 was increased 2-fold as compared with controls. The advantage of the method
      is that it is tagless, does not require additional purification steps, and is
      extremely sensitive. The approach can be multiplexed and used for identification
      of novel substrates/inhibitors of the RAS.

PMID- 16103260
TI  - Vascular sensitivity to phenylephrine in rats submitted to anaerobic training and
      nandrolone treatment.
AB  - The effect of anaerobic physical training and nandrolone treatment on the
      sensitivity to phenylephrine in thoracic aorta and lipoprotein plasma levels of
      rats was studied. Sedentary and trained male Wistar rats were treated with
      vehicle or nandrolone (5 mg/kg IM; twice per week) for 6 weeks. Training was
      performed by jumping into water (4 sets, 10 repetitions, 30-second rest, 50% to
      70% body weight load, 5 days/week, 6 weeks). Two days after the last training
      session, the animals were killed and blood samples for lipoprotein dosage were
      obtained. Thoracic aorta was isolated and concentration-effect curves of
      phenylephrine were performed in intact endothelium and endothelium-denuded aortic
      rings in the absence or presence of NG-L-arginine-methyl ester. No changes were
      observed in endothelium-denuded aortic rings. However, in endothelium-intact
      thoracic aorta, anaerobic physical training induced subsensitivity to
      phenylephrine (pD2=7.11+/-0.07) compared with sedentary group (7.55+/-1.74), and
      this effect was canceled by the inhibition of nitric oxide synthesis. No
      difference was observed between trained (7.22+/-0.07) and sedentary (7.28+/-0.09)
      groups treated with nandrolone. Anaerobic training induced an increase in high
      density lipoprotein levels in vehicle-treated rats, but there were no changes in
      nandrolone-treated groups. Training associated with nandrolone induced an
      increase in low-density lipoprotein levels but no change in the other groups. If
      altering endothelium-dependent vasodilatation is considered to be a beneficial
      adaptation to anaerobic physical training, it is concluded that nandrolone
      treatment worsens animals' endothelial function, and this effect may be related
      to lipoprotein blood levels.

PMID- 16103262
TI  - Radioimmunoassays, ouabain-like material, and ouabain.

PMID- 16103263
TI  - Renin inhibition: new potential for an old therapeutic target.

PMID- 16103264
TI  - Aliskiren, a human renin inhibitor, ameliorates cardiac and renal damage in
      double-transgenic rats.
AB  - We tested the hypothesis that the renin inhibitor aliskiren ameliorates organ
      damage in rats transgenic for human renin and angiotensinogen genes (double
      transgenic rat [dTGR]). Six-week-old dTGR were matched by albuminuria (2 mg per
      day) and divided into 5 groups. Untreated dTGR were compared with aliskiren (3
      and 0.3 mg/kg per day)-treated and valsartan (Val; 10 and 1 mg/kg per day)
      treated rats. Treatment was from week 6 through week 9. At week 6, all groups had
      elevated systolic blood pressure (BP). Untreated dTGR showed increased BP (202+/
      4 mm Hg), serum creatinine, and albuminuria (34+/-5.7 mg per day) at week 7. At
      week 9, both doses of aliskiren lowered BP (115+/-6 and 139+/-5 mm Hg) and
      albuminuria (0.4+/-0.1 and 1.6+/-0.6 mg per day) and normalized serum creatinine.
      Although high-dose Val lowered BP (148+/-4 mm Hg) and albuminuria (2.1+/-0.7 mg
      per day), low-dose Val reduced BP (182+/-3 mm Hg) and albuminuria (24+/-3.8 mg
      per day) to a lesser extent. Mortality was 100% in untreated dTGR and 26% in Val
      (1 mg/kg per day) treated rats, whereas in all other groups, survival was 100%.
      dTGR treated with low-dose Val had cardiac hypertrophy (4.4+/-0.1 mg/g),
      increased left ventricular (LV) wall thickness, and diastolic dysfunction. LV
      atrial natriuretic peptide and beta-myosin heavy chain mRNA, albuminuria,
      fibrosis, and cell infiltration were also increased. In contrast, both aliskiren
      doses and the high-dose Val lowered BP to a similar extent and more effectively
      than low-dose Val. We conclude that in dTGR, equieffective antihypertensive doses
      of Val or aliskiren attenuated end-organ damage. Thus, renin inhibition compares
      favorably to angiotensin receptor blockade in reversing organ damage in dTGR.

PMID- 16103265
TI  - Sex differences in cardiovascular disease and hypertension: involvement of the
      renin-angiotensin system.

PMID- 16103266
TI  - Association of NEDD4L ubiquitin ligase with essential hypertension.
AB  - NEDD4L is a ubiquitin ligase that controls cell surface expression of kidney
      epithelial Na+ channels by ubiquitin-mediated endocytosis and lysosome targeting.
      Thus, it is a significant determinant of Na+ reabsorption in the distal nephron.
      The NEDD4L gene is located on human chromosome 18q21 within several blood
      pressure quantitative trait loci, including those for familial orthostatic
      hypotension, essential hypertension, pulse pressure, and systolic blood pressure
      response to postural challenge. Because of the importance of NEDD4L to Na+
      balance, many of these studies have proposed that mutations in NEDD4L may be
      responsible for these blood pressure phenotypes. To test this hypothesis, we fine
      mapped the NEDD4L region in 2 families with orthostatic hypotension, which we
      previously reported to be linked to human chromosome 18q21 but failed to
      implicate NEDD4L in these families. We also typed multiple NEDD4L single
      nucleotide polymorphisms (SNPs) in a collection of US whites, Greek whites, and
      African-Americans individuals with essential hypertension. A significant
      association between several SNPs and hypertension was observed in all 3
      populations. One of the SNPs associated in African Americans is known to result
      in premature truncation of the NEDD4L protein. Thus, genetic variation in NEDD4L
      may play a role in the development or progression of some forms of abnormal blood
      pressure.

PMID- 16103267
TI  - Potassium supplementation reduces cardiac and renal hypertrophy independent of
      blood pressure in DOCA/salt mice.
AB  - We have demonstrated previously that deoxycorticosterone acetate (DOCA)/salt
      induces cardiac hypertrophy and left ventricular dysfunction independent of blood
      pressure (BP) in 1-renin gene mice. Because these mice also develop hypokalemia
      and metabolic alkalosis caused by mineralocorticoid excess, we investigated
      whether correcting hypokalemia by dietary potassium supplementation would prevent
      the DOCA/salt-induced cardiac hypertrophy, cardiac dysfunction, and
      electrocardiographic changes in normotensive, 1-renin gene and hypertensive, 2
      renin gene mice. All mice were studied after 5 weeks of DOCA and salt
      administration. Potassium was given by adding 0.4 or 0.6% KCl to the drinking
      water. Our results show that correction of hypokalemia and metabolic alkalosis
      prevents cardiac hypertrophy and normalizes cardiac function without affecting BP
      in normotensive, 1-renin gene mice. In hypertensive, 2-renin gene mice, potassium
      supplementation induces a significant decrease in BP. The decrease in BP and
      correction of kalemia are associated with a significant but partial correction of
      cardiac hypertrophy. In both group of mice, electrocardiographic alterations were
      measured after administration of DOCA/salt, which could be corrected by potassium
      supplementation. Thus, these results show that correction of hypokalemia and
      metabolic alkalosis does prevent the development of cardiac hypertrophy and
      normalizes cardiac function independent of BP in normotensive, 1-renin gene mice
      that receive excess mineralocorticoid and salt. In 2-renin gene, hypertensive
      mice, potassium supplementation also prevents the development of cardiac
      hypertrophy, but the effect cannot be separated from the decrease in BP.

PMID- 16103268
TI  - Sex difference in vascular injury and the vasoprotective effect of valsartan are
      related to differential AT2 receptor expression.
AB  - The angiotensin II type 2 (AT2) receptor is upregulated in pathological
      conditions such as vascular injury and exerts antagonistic effects against AT1
      receptor-mediated actions. We examined the possibility that the sex difference in
      vascular remodeling is associated with altered AT2 receptor expression, which is
      located on the X chromosome. In this study, we examined this possibility by using
      AT2 receptor-null (Agtr2-) mice. Vascular injury was induced by polyethylene cuff
      placement around the femoral artery of wild-type (Agtr2+) and Agtr2- mice. In
      Agtr2+ mice, AT2 receptor expression in the injured artery was enhanced, and this
      increase was greater in female than in male mice, with no significant difference
      in AT1 receptor expression between male and female mice. Increases in neointimal
      formation, DNA synthesis, expression of monocyte chemoattractant protein-1,
      production of superoxide anion, and NADPH oxidase activity in the injured artery
      were attenuated in female compared with male mice. These parameters were
      augmented in Agtr2- mice, whereas the sex differences in these parameters were
      smaller in Agtr2- than in Agtr2+ mice. Treatment with a nonhypotensive dose of
      the AT1 receptor blocker valsartan decreased these parameters significantly in
      Agtr2+ mice, and these inhibitory effects of valsartan were greater in female
      mice. This sex difference in valsartan's inhibitory effect was less marked in
      Agtr2- mice. Our results suggest that the sex difference in response to vascular
      injury could be at least partially attributed to the exaggerated AT2 receptor
      expression in the injured vessel in female mice.

PMID- 16103269
TI  - Adenosine inhibits PDGF-induced growth of human glomerular mesangial cells via
      A(2B) receptors.
AB  - The objectives of the present study were to determine whether adenosine
      attenuates proliferation of glomerular mesangial cells (GMCs), which adenosine
      receptor (AR) mediates the antimitogeneic actions of adenosine, and the cellular
      mechanisms by which adenosine inhibits growth of GMCs. Studies were conducted in
      both human and rat GMCs. Platelet-derived growth factor (PDGF)-BB (25 ng/mL)
      increased DNA synthesis ([3H]thymidine incorporation), cellular proliferation
      (cell number), collagen synthesis ([3H]proline incorporation), and mitogen
      activated protein kinase (MAPK) activity, and these effects were attenuated by 2
      chloroadenosine (nonselective AR agonist) and 5'-N-methylcarboxamidoadenosine
      (MECA; nonselective AR agonist), but not by N6-cyclopentyladenosine (selective A1
      AR agonist), AB-N-MECA (selective A3 AR agonist), or CGS21680 (selective A(2A) AR
      agonist). KF17837 (selective A(2A/B) AR antagonist) and 1,3-dipropyl-8-p
      sulfophenylxanthine (nonselective AR antagonist), but not 8-cyclopentyl-1,3
      dipropylxanthine (selective A1 AR antagonist), blocked the growth-inhibitory
      effects of 2-chloroadenosine and 5'-N-MECA. Antisense, but not sense or
      scrambled, oligonucleotides to the A(2B) receptor increased both basal and PDGF
      induced DNA synthesis, cell proliferation, and collagen synthesis, and the growth
      inhibitory effects of 2-chloroadenosine, 5'-N-MECA, and erythro-9-(2-hydroxy-3
      nonyl)adenine (inhibitor of adenosine deaminase) plus iodotubercidin (inhibitor
      of adenosine kinase) were abolished by antisense, but not scrambled or sense,
      oligonucleotides to the A(2B) receptor. We conclude that adenosine causes
      inhibition of GMC growth by activating A(2B) receptors coupled to inhibition of
      MAPK activity. A(2B) receptors may play an important role in regulating
      glomerular remodeling associated with GMC proliferation. Pharmacological or
      molecular biologic activation of A(2B) receptors may prevent glomerular
      remodeling associated with glomerulosclerosis, renal disease, and abnormal growth
      associated with hypertension and diabetes.

PMID- 16103270
TI  - The kidney as a determinant of genetic hypertension: evidence from renal
      transplantation studies.

PMID- 16103271
TI  - Correlates of systolic hypertension in patients with chronic kidney disease.
AB  - Hypertension in patients with chronic kidney disease (CKD) is predominantly
      systolic. The contribution of risk factors for hypertension to the overall
      systolic blood pressure (BP) is unknown. To study the relationship between risk
      factors for hypertension and systolic BP in patients with CKD, 232 veterans (mean
      age 67 years; 96% men; 20% black; 39% with diabetes mellitus; estimated
      glomerular filtration rate [GFR] 48 mL/min per 1.73 m2) had clinic (routine and
      standardized measurements) and out-of-clinic (home and 24-hour ambulatory) BPs
      recorded. In multivariate analysis, using 17 risk factors, the log of the urine
      protein/creatinine ratio was the strongest predictor of systolic BP regardless of
      the BP measurement technique. The strength of the relationship between
      proteinuria and systolic BP was in the order ambulatory > home > standardized
      clinic > routine clinic BP measurement. Other independent predictors were age,
      race, and number of antihypertensive drugs used, and the model fit was better for
      out-of-clinic than clinic BP recordings. Estimated GFR was not an independent
      predictor of systolic BP by any technique. Nocturnal dipping was associated with
      higher estimated GFR, higher serum albumin, younger age, and less proteinuria.
      Proteinuria is the most important correlate of systolic BP in older men, the
      strongest relationship of which was with ambulatory and home systolic BP. Out-of
      clinic BP recordings correlate better with target organ damage, as measured by
      proteinuria, and may be of greater clinical value than clinic BP recordings in
      predicting hypertension-related outcomes such as end-stage renal disease and
      death.

PMID- 16103272
TI  - Arterial aging: is it an immutable cardiovascular risk factor?
AB  - Age is the dominant risk factor for cardiovascular diseases. However, until
      recently, convincing mechanistic or molecular explanations for the increased
      cardiovascular risks conferred by aging have been elusive. Aging is associated
      with alterations in a number of structural and functional properties of large
      arteries, including diameter, wall thickness, wall stiffness, and endothelial
      function. Emerging evidence indicates that these age-associated changes are also
      accelerated in the presence of cardiovascular diseases, and that these changes
      are themselves risk factors for the appearance or progression of these diseases.
      In this review, the evidence demonstrating that arterial aging is accelerated in
      cardiovascular diseases and that accelerated arterial aging is a risk factor for
      adverse cardiovascular outcomes is briefly reviewed, and selected advances in
      vascular biology that provide insights into the mechanisms that may underlie the
      increased risks conferred by arterial aging are summarized. Remarkably, a host of
      biochemical, enzymatic, and cellular alterations that are operative in
      accelerated arterial aging have also been implicated in the pathogenesis and
      progression of arterial diseases. These vascular alterations are thus putative
      candidates that could be targeted by interventions aimed at attenuating arterial
      aging, similar to the lifestyle and pharmacological interventions that have
      already been proven effective. Therefore, the notion that aging is a
      chronological process and that its risky components cannot be modulated is no
      longer tenable. It is our hope that a greater appreciation of the links between
      arterial aging and cardiovascular diseases will stimulate further investigation
      into strategies aimed at preventing or retarding arterial aging.

PMID- 16103273
TI  - Coffee blunts mental stress-induced blood pressure increase in habitual but not
      in nonhabitual coffee drinkers.
AB  - Coffee is widely consumed, especially during mental stress conditions.
      Cardiovascular impact of coffee remains debated because the underlying mechanisms
      of action are complex. We reported previously differential cardiovascular
      stimulation of coffee at rest depending on habitual consumption. The present
      study was designed to evaluate the effects of coffee on cardiovascular response
      to mental stress. In 15 healthy volunteers (6 habitual, 9 nonhabitual coffee
      drinkers), we assessed the effect of mental stress on blood pressure (BP), heart
      rate (HR), and muscle sympathetic activity (MSA) before and after a triple
      espresso, intravenous caffeine, and placebo in the same subjects. Under baseline
      conditions, mental stress significantly increases MSA (+2.5+/-0.7 volts per
      minute; +14.1+/-10.3%), systolic (+11.6+/-4.1 mm Hg) and diastolic BP (+6.4+/-2.0
      mm Hg), and HR (+9.6+/-1.8 minutes(-1)). In nonhabitual coffee drinkers, a triple
      espresso but not caffeine induced an additional increase in systolic BP (+9+/-6.3
      mm Hg; P=0.003) during mental stress, whereas in habitual drinkers, the stress
      induced BP increase was blunted (+4+/-3.9 mm Hg; P=NS). As a result, nonhabitual
      coffee drinkers experienced significantly higher BP during mental stress than
      habitual drinkers (151+/-17.9/83+/-5.6 mm Hg versus 130+/-7.8/74+/-6.7 mm Hg;
      P<0.05). Caffeine induced similar effects in habitual and nonhabitual coffee
      drinkers at rest and during mental stress. The response to the cold pressor test
      was not influenced by coffee drinking in both groups. In conclusion, in
      nonhabitual coffee drinkers, coffee enhances the cardiovascular response to
      mental stress with an additional increase in systolic BP, whereas in habitual
      drinkers, the response is blunted. Caffeine alone does not exert any potentiating
      effect, confirming that ingredients other than caffeine are partially responsible
      for the stimulating effect of coffee on the cardiovascular system.

PMID- 16103274
TI  - Non-narcotic analgesic dose and risk of incident hypertension in US women.
AB  - Acetaminophen, ibuprofen, and aspirin are the most commonly used drugs in the
      United States. Although the frequency of their use has been associated with
      hypertension, prospective data examining the dose of these drugs and risk of
      hypertension are lacking. Furthermore, whether certain indications for analgesic
      use, particularly headache, mediate the association is unclear. We conducted 2
      prospective cohort studies among older women 51 to 77 years of age (n=1903) from
      the Nurses' Health Study I and younger women 34 to 53 years of age (n=3220) from
      the Nurses' Health Study II who completed detailed supplemental questionnaires
      pertaining to their analgesic use and who did not have hypertension at baseline.
      We analyzed incident hypertension according to categories of average daily dose
      of acetaminophen, nonsteroidal anti-inflammatory drugs, and aspirin. Information
      on indications for analgesic use as well as relevant confounders was also
      gathered prospectively. Compared with women who did not use acetaminophen, the
      multivariable adjusted relative risk for those who took >500 mg per day was 1.93
      (1.30 to 2.88) among older women and 1.99 (1.39 to 2.85) among younger women. For
      nonsteroidal anti-inflammatory drugs, similar comparisons yielded multivariable
      relative risks of 1.78 (1.21 to 2.61) among older women and 1.60 (1.10 to 2.32)
      among younger women. These associations remained significant among women who did
      not report headache. Aspirin dose was not significantly associated with
      hypertension. Higher daily doses of acetaminophen and nonsteroidal anti
      inflammatory drugs independently increase the risk of hypertension in women.
      Because acetaminophen and nonsteroidal anti-inflammatory drugs are commonly used,
      they may contribute to the high prevalence of hypertension in the United States.

PMID- 16103275
TI  - Superoxide contributes to development of salt sensitivity and hypertension
      induced by nitric oxide deficiency.
AB  - This study was performed to examine the role of superoxide (O2-) in the
      development of salt sensitivity and hypertension induced by inhibition of nitric
      oxide (NO) generation. Male Sprague-Dawley rats were fed with diet containing
      either normal salt (NS) (0.4% NaCl) or high salt (HS) (4% NaCl). These rats were
      treated with or without an NO synthase inhibitor, nitro-L-arginine methylester (L
      NAME) (15 mg/kg/d) and O2- scavenger, tempol (30 mg/kg per day) in the drinking
      water for 4 weeks. Systolic blood pressure (SBP) was measured by tail-cuff
      plethysmography and urine collection was performed during the course of
      experimental periods. At the end of 4 weeks, L-NAME treatment resulted in greater
      increases in SBP in HS rats (127+/-2 to 172+/-3 mm Hg; n=8) than in NS rats
      (130+/-2 to 156+/-2 mm Hg; n=9). Co-administration of tempol with L-NAME markedly
      attenuated these SBP responses to a similar level in both HS (128+/-3 to 147+/-2
      mm Hg; n=8) and NS rats (126+/-2 to 142+/-3 mm Hg; n=8). Urinary 8-isoprostane
      excretion (UIsoV) increased in response to L-NAME treatment that was higher in HS
      (10.6+/-0.5 to 21.5+/-0.8 ng/d) than in NS rats (10.8+/-0.7 to 16.9+/-0.6 ng/d).
      Co-treatment with tempol completely abolished these UIsoV responses to L-NAME in
      both HS and NS rats but did not alter urinary H2O2 excretion rate. The decreases
      in urinary nitrate/nitrite excretion in response to L-NAME treatment were not
      altered by co-administration of tempol in both HS and NS rats. These data suggest
      that enhancement of O2- activity during NO inhibition contributes to the
      development of salt sensitivity that is associated with NO-deficient
      hypertension.

PMID- 16103276
TI  - Investigating the putative glycine hinge in Shaker potassium channel.
AB  - The crystal structure of an open potassium channel reveals a kink in the inner
      helix that lines the pore (Jiang, Y.X., A. Lee, J.Y. Chen, M. Cadene, B.T. Chait,
      and R. MacKinnon. 2002. Nature 417:523-526). The putative hinge point is a highly
      conserved glycine residue. We examined the role of the homologous residue
      (Gly466) in the S6 transmembrane segment of Shaker potassium channels. The
      nonfunctional alanine mutant G466A will assemble, albeit poorly, with wild-type
      (WT) subunits, suppressing functional expression. To test if this glycine residue
      is critical for activation gating, we did a glycine scan along the S6 segment in
      the background of G466A. Although all of these double mutants lack the higher
      level glycosylation that is characteristic of mature Shaker channels, one
      (G466A/V467G) is able to generate voltage-dependent potassium current. Surface
      biotinylation shows that functional and nonfunctional constructs containing G466A
      express at comparable levels in the plasma membrane. Compared with WT channels,
      the shifted-glycine mutant has impairments in voltage-dependent channel opening,
      including a right-shifted activation curve and a decreased rate of activation.
      The double mutant has relatively normal open-channel properties, except for a
      decreased affinity for intracellular blockers, a consequence of the loss of the
      side chain of Val467. Control experiments with the double mutants M440A/G466A and
      G466A/V467A suggest that the flexibility provided by Gly466 is more important for
      channel function than its small size. Our results support roles for Gly466 both
      in biogenesis of the channel and as a hinge in activation gating.

PMID- 16103277
TI  - The NH2 terminus of RCK1 domain regulates Ca2+-dependent BK(Ca) channel gating.
AB  - Large conductance, voltage- and Ca2+-activated K+ (BK(Ca)) channels regulate
      blood vessel tone, synaptic transmission, and hearing owing to dual activation by
      membrane depolarization and intracellular Ca2+. Similar to an archeon Ca2+
      activated K+ channel, MthK, each of four alpha subunits of BK(Ca) may contain two
      cytosolic RCK domains and eight of which may form a gating ring. The structure of
      the MthK channel suggests that the RCK domains reorient with one another upon
      Ca2+ binding to change the gating ring conformation and open the activation gate.
      Here we report that the conformational changes of the NH2 terminus of RCK1 (AC
      region) modulate BK(Ca) gating. Such modulation depends on Ca2+ occupancy and
      activation states, but is not directly related to the Ca2+ binding sites. These
      results demonstrate that AC region is important in the allosteric coupling
      between Ca2+ binding and channel opening. Thus, the conformational changes of the
      AC region within each RCK domain is likely to be an important step in addition to
      the reorientation of RCK domains leading to the opening of the BK(Ca) activation
      gate. Our observations are consistent with a mechanism for Ca2+-dependent
      activation of BK(Ca) channels such that the AC region inhibits channel activation
      when the channel is at the closed state in the absence of Ca2+; Ca2+ binding and
      depolarization relieve this inhibition.

PMID- 16103278
TI  - "Optical patch-clamping": single-channel recording by imaging Ca2+ flux through
      individual muscle acetylcholine receptor channels.
AB  - We describe an optical technique using total internal reflection fluorescence
      (TIRF) microscopy to obtain simultaneous and independent recordings from numerous
      ion channels via imaging of single-channel Ca2+ flux. Muscle nicotinic
      acetylcholine (ACh) receptors made up of alphabetagammadelta subunits were
      expressed in Xenopus oocytes, and single channel Ca2+ fluorescence transients
      (SCCaFTs) were imaged using a fast (500 fps) electron-multiplied c.c.d. camera
      with fluo-4 as the indicator. Consistent with their arising through openings of
      individual nicotinic channels, SCCaFTs were seen only when a nicotinic agonist
      was present in the bathing solution, were blocked by curare, and increased in
      frequency as roughly the second power of [ACh]. Their fluorescence amplitudes
      varied linearly with membrane potential and extrapolated to zero at about +60 mV.
      The rise and fall times of fluorescence were as fast as 2 ms, providing a kinetic
      resolution adequate to characterize channel gating kinetics; which showed mean
      open times of 7.9 and 15.8 ms when activated, respectively, by ACh or
      suberyldicholine. Simultaneous records were obtained from >400 channels in the
      imaging field, and we devised a novel "channel chip" representation to depict the
      resultant large dataset as a single image. The positions of SCCaFTs remained
      fixed (<100 nm displacement) over tens of seconds, indicating that the nicotinic
      receptor/channels are anchored in the oocyte membrane; and the spatial
      distribution of channels appeared random without evidence of clustering. Our
      results extend single-channel TIRFM imaging to ligand-gated channels that display
      only partial permeability to Ca2+, and demonstrate an order-of-magnitude
      improvement in kinetic resolution. We believe that functional single-channel
      imaging opens a new approach to ion channel study, having particular advantages
      over patch-clamp recording in that it is massively parallel, and provides high
      resolution spatial information that is inaccessible by electrophysiological
      techniques.

PMID- 16103279
TI  - Department of Surgery, University of Wisconsin-Madison.

PMID- 16103280
TI  - The academic department of surgery: between Scylla and Charybdis.

PMID- 16103281
TI  - The evolving role of staging laparoscopy in the treatment of colorectal hepatic
      metastasis.
AB  - HYPOTHESIS: Laparoscopy is an increasingly important tool in the staging and
      treatment of hepatic malignancies. This study evaluates the effect of staging
      laparoscopy (SL) using intraoperative ultrasonography (IOUS) on the regional
      treatment of isolated hepatic colorectal metastasis. DESIGN: Analytic cohort
      study. SETTING: Tertiary care center. PATIENTS: Consecutive patients who have a
      colorectal metastasis confined to the liver and selected for surgical regional
      treatment. INTERVENTIONS: All patients underwent preoperative evaluation followed
      by SL/IOUS. Operative plans were based on preoperative imaging and were either
      carried out or altered intraoperatively according to SL/IOUS findings. MAIN
      OUTCOME MEASURE: Effect of SL/IOUS on surgical management. RESULTS: Between
      September 1996 and May 2004 one hundred fifty-two SL/IOUSs were performed in 136
      patients (77 males and 59 females), who had a mean (SD) age of 63 (11) years.
      Data sets were complete in 138 events. All patients had isolated hepatic disease
      as defined by preoperative computed tomography in 152 (100%) and positron
      emission tomography in 107 (70%). Staging laparoscopy/IOUS identified surgically
      untreatable disease in 34 events (25%) because of peritoneal metastases (n = 15),
      nodal involvement (n = 11), diffuse hepatic disease (n = 5), no identifiable
      disease (n = 2), and untreatable disease (n = 1). Laparoscopic treatment events
      included radiofrequency ablations (n = 78), hepatic artery pump implantations (n
      = 40), resections (n = 26), and combined procedures (n = 37). Overall, SL/IOUS
      changed the treatment plan in 66 (48%) of 138 of events. This includes 32 (23%)
      of 138 events in which SL/IOUS findings significantly altered the actual
      procedure performed relative to the preoperative plan. Three minor complications
      occurred in the SL/IOUS-only group with a mean (SD) hospital stay of 1.3 (1)
      days. CONCLUSION: In the regional management of isolated colorectal hepatic
      metastasis, SL/IOUS avoids unnecessary laparotomies and influences definitive
      surgical intervention in a substantial proportion of patients.

PMID- 16103282
TI  - Improved human pancreatic islet isolation for a prospective cohort study of islet
      transplantation vs best medical therapy in type 1 diabetes mellitus.
AB  - HYPOTHESIS: A local multiorgan donor pancreas procurement program can provide a
      source for optimized isolation of purified viable islets for transplantation into
      patients with type 1 diabetes mellitus receiving best medical therapy. DESIGN:
      Prospective before-after cohort study. SETTING: Tertiary referral center.
      PATIENTS: Glycemic control was assessed in 10 patients with diabetes-induced
      renal dysfunction who were enrolled in a best medical therapy program and then
      crossed over to islet transplantation. INTERVENTIONS: Thirty human pancreata were
      retrieved from local multiorgan donors and consecutively processed with
      intraductal collagenase perfusion, continuous digestion, and density gradient
      purification (group 1, n = 9) or similarly processed but impure tissue fractions
      cultured in vitro and then repurified to retrieve additional islets (group 2, n =
      21). Islets were implanted by percutaneous portal embolization, providing more
      than 10 000 islet equivalents (IE) per kilogram of body weight (infusions from 1
      3 donors per patient) under cover of antithymocyte globulin, sirolimus, or
      mycophenolate mofetil and tacrolimus. MAIN OUTCOME MEASURES: Islet yields,
      purity, and cell viability (caspase 3, terminal deoxynucleotidyl transferase
      mediated biotin-deoxyuridine 5-triphosphate nick-end labeling stain, and insulin
      secretion in vitro) were compared. In patients, monitored metabolic parameters
      were C-peptide secretion, insulin requirements, glycemic excursion, and
      hemoglobin A(1c) (HbA(1c)). RESULTS: For group 1 vs group 2, no differences were
      observed in pancreas age (43 vs 44 years), cold storage (5 vs 4 hours), or weight
      (73 vs 82 g). Group 2 yielded 453 690 IE vs 214 109 IE in group 1 (P = .002).
      Grafts contained 50% or more endocrine cells in both groups. No difference
      occurred in cell viability or insulin secretion. Islets from 90% of group 2
      pancreata met release criteria for transplantation. C-peptide secretion was
      detected in all recipients and persisted with a median follow-up to 12 months
      (range, 6-21 months) after full islet transplantation. Daily insulin dependence
      was reversed in all patients for at least 3 months. Five patients resumed small
      insulin doses. Compared with the best care program, all patients had improved
      metabolic stability. The mean +/- SE HbA(1c) level at entry into the study was
      7.8% +/- 0.5%, and this decreased to 6.9% +/- 0.2% after best care (P = .38) and
      further to 6.2% +/- 0.2% at 6 months after transplantation (P = .002 vs entry; P
      = .15 vs best care; analysis of variance). CONCLUSIONS: Local pancreas donor
      retrieval with islet isolation and culture conditioning enabled an offer of
      islets for transplantation for 90% of consecutively processed pancreata. Isolated
      islets secreted insulin during prolonged follow-up after implantation into
      patients, yielding metabolic control comparable with that achieved by best
      medical therapy.

PMID- 16103283
TI  - Use of serum bicarbonate measurement in place of arterial base deficit in the
      surgical intensive care unit.
AB  - HYPOTHESIS: Serum bicarbonate (HCO(3)) measurement may accurately and reliably be
      substituted for the arterial base deficit (BD) assay in the surgical intensive
      care unit (ICU). DESIGN: Retrospective criterion standard analysis. SETTING:
      Surgical ICU in a tertiary care facility. PATIENTS: Consecutive sample of non
      trauma-related surgical ICU admissions from January 1996 to January 2004 with
      simultaneously obtained serum HCO(3) and arterial BD levels. MAIN OUTCOME
      MEASURES: Correlation between HCO(3) and BD at admission and during the ICU stay;
      predictive value of serum HCO(3) for significant metabolic acidosis and ICU
      mortality. RESULTS: The study included 2291 patients with 26 063 sets of paired
      laboratory data. The mean +/- SD age was 52 +/- 16 years and mean ICU stay was
      5.8 +/- 9.8 days. There were 174 ICU deaths (8%). Serum HCO(3) levels showed
      significant correlation with arterial BD levels both at admission (r = 0.85, R(2)
      = 0.72, P<.001) and throughout the ICU stay (r = 0.88, R(2) = 0.77, P<.001).
      Serum HCO(3) reliably predicted the presence of significant metabolic acidosis
      (BD > 5) with an area under the receiver operating characteristic curve (AUC) of
      0.93 at admission and 0.95 overall (both P<.001), outperforming pH (AUC, 0.80),
      anion gap (AUC, 0.70), and lactate (AUC, 0.70). The admission serum HCO(3) level
      predicted ICU mortality as accurately as the admission arterial BD (AUCs of 0.68
      and 0.70, respectively) and more accurately than either admission pH or anion
      gap. CONCLUSIONS: Serum HCO(3) provides equivalent information to the arterial BD
      and may be used as an alternative predictive marker or guide to resuscitation.
      Low HCO(3) levels should prompt immediate metabolic acidosis evaluation and
      management.

PMID- 16103284
TI  - Preoperative oral antibiotics in colorectal surgery increase the rate of
      Clostridium difficile colitis.
AB  - HYPOTHESIS: Bowel preparation traditionally consists of cathartics, oral
      antibiotics, and intravenous antibiotics. We hypothesize that the use of oral
      antibiotics in bowel preparation results in a higher rate of postoperative
      Clostridium difficile colitis. DESIGN: Retrospective case-controlled study of
      elective colon surgery patients; January 1997 to June 2003. SETTING: Tertiary
      care veterans administration hospital. PATIENTS: Records of patients who
      underwent elective colorectal surgery (n = 304) were reviewed. Patients with
      bowel obstruction or emergent operation were excluded. MAIN OUTCOME MEASURE:
      Detection of C difficile toxin A/B by enzyme-linked immunosorbent assay in a
      stool specimen within 30 days of surgery. RESULTS: All 304 patients received both
      cathartics and intravenous antibiotics. Of 304 patients, 107 (35.1%) received
      oral antibiotics. The rate of postoperative C difficile colitis was 4.2% in the
      entire study population. The rate of C difficile infection was higher in patients
      who received oral antibiotics (7.4%) compared with patients who did not receive
      oral antibiotics (2.6%; P = .03). There were no C difficile-related mortalities.
      CONCLUSION: Oral nonabsorbable antibiotics in bowel preparation resulted in a
      higher rate of C difficile infection. This may be due to the additional effect of
      oral antibiotics on normal bowel flora. We recommend that oral nonabsorbable
      antibiotics not be used in preoperative bowel preparation regimens since
      postoperative C difficile infection can lead to additional morbidity, length of
      stay, and hospital costs.

PMID- 16103285
TI  - Patient sex and success of peripheral percutaneous transluminal arterial
      angioplasty.
AB  - HYPOTHESIS: Female sex negatively affects the durability of percutaneous
      angioplasty of native arteries supplying the lower extremity. DESIGN: Outcome
      analysis of the results of percutaneous angioplasty of lower extremity arteries
      in a single vascular surgery practice. SETTING: University-affiliated community
      hospital. PATIENTS: All patients undergoing percutaneous intervention on lower
      extremity arteries during 10 years. INTERVENTIONS: Indication for intervention,
      anatomic site of intervention, placement of percutaneous stents, and length of
      lesion undergoing angioplasty were noted. Patient demographics and risk factors
      were identified. MAIN OUTCOME MEASURES: Results were analyzed by sex. Kaplan
      Meier life tables were plotted and differences between groups tested by the log
      rank method. A Cox proportional hazards regression model was used to perform the
      multivariate analysis. RESULTS: During 10 years, 351 angioplasties were performed
      in 248 patients, 173 in women and 178 in men. There was no difference between men
      and women in indication for intervention, length and type of lesion treated, or
      quality of distal runoff. Univariate survival analysis identified a difference in
      duration of patency between men and women (P = .047). However, multivariate
      analysis demonstrated no significant difference in duration of patency between
      men and women (P = .18). Iliac angioplasty and adequate distal runoff were
      positive predictors of long-term patency (P<.001 for both). CONCLUSIONS: There
      appears to be no significant difference in the durability of angioplasty between
      men and women. However, location of angioplasty and adequacy of distal runoff may
      be useful in determining when to use angioplasty.

PMID- 16103286
TI  - Magnetic resonance imaging is not needed to clear cervical spines in blunt trauma
      patients with normal computed tomographic results and no motor deficits.
AB  - HYPOTHESIS: Trauma patients with normal motor examination results and normal
      cervical spine helical computed tomographic (CT) scans with sagittal
      reconstructions do not have significant cervical spine injury. DESIGN:
      Prospectively collected registry data. SETTING: Level II community-based trauma
      center. PATIENTS: All patients admitted to the trauma service from January 1,
      1999, to December 31, 2003. MAIN OUTCOME MEASURES: Injury detected by CT and/or
      magnetic resonance imaging (MRI) of the cervical spine. Neurologic examination
      and need for surgery were secondary outcomes. RESULTS: During the study period,
      2854 trauma patients were admitted, of whom 91.2% had blunt trauma. Of these
      patients, 56.2% had a closed head injury. One hundred patients had cervical spine
      and/or spinal cord injuries. Eighty-five patients had a cervical spine injury
      diagnosed by CT. Fifteen patients had admission neurologic deficits not seen on
      CT, and 7 of these patients had non-bony abnormalities on MRI. Ninety-three
      patients had a normal admission motor examination result, a CT result negative
      for trauma, and persistent cervical spine pain, and were examined with MRI. All
      MRI examination results were negative for clinically significant injury.
      Seventeen patients had MRIs that showed degenerative disc disease, and 6 had
      spinal canal stenosis secondary to ossification. Twelve comatose patients
      (Glasgow Coma Scale score, <9), moving all 4 extremities on arrival, with normal
      CT results of the cervical spine, were examined with MRI. All of these MRI
      examination results were negative for injury. None of the patients experienced
      neurologic deterioration. No patient required operative management of spinal
      injury. CONCLUSION: Blunt trauma patients with normal motor examination results
      and normal CT results of the cervical spine do not require further radiologic
      examination before clearing the cervical spine.

PMID- 16103287
TI  - Hemodynamically "stable" patients with peritonitis after penetrating abdominal
      trauma: identifying those who are bleeding.
AB  - HYPOTHESIS: Despite initial presentation, hemodynamically stable patients with
      penetrating abdominal trauma may have significant ongoing hemorrhage and major
      intra-abdominal injuries requiring emergent surgical intervention. DESIGN: Cohort
      analytic study. SETTING: Academic, level I trauma center. PATIENTS: One hundred
      thirty-nine consecutive hemodynamically stable patients with penetrating
      abdominal trauma in whom peritonitis was the sole indication for laparotomy. MAIN
      OUTCOME MEASURES: The primary outcome was the amount of blood initially found at
      laparotomy. Secondary outcomes included additional intraoperative blood loss,
      intraoperative hypotension, transfusion, fluid, and vasopressor requirement; need
      for admission to the intensive care unit and mechanical ventilation;
      complications; survivor length of stay in the hospital and intensive care unit;
      and mortality. RESULTS: The admission systolic blood pressure (mean +/- SD, 131
      +/- 22 mm Hg) and heart rate (mean +/- SD, 91 +/- 22 beats/min) were normal.
      Median time from peritonitis to incision was 40 minutes. Ninety-seven percent of
      patients had intra-abdominal injury, including 81%, hollow visceral; 36%, solid
      organ; and 11%, vascular injury. Though most patients had less than 750 mL(3) of
      blood found initially at laparotomy, there were 11% with 750 to 1500 mL(3) and 7%
      with 1500 mL(3) or more. Intraoperative hypotension (25%) and blood transfusion
      (39%) were common. Postoperatively, 40% of patients required intensive care (78%
      of them requiring mechanical ventilation) and 19% required additional transfusion
      within 24 hours. Complications occurred in 25% of patients, with intra-abdominal
      abscess (12%) and wound infection (7%) being the most common. Three patients
      died, 2 of exsanguination and 1 of multisystem organ failure. CONCLUSIONS:
      Following penetrating abdominal trauma, peritonitis should be a trigger for
      emergent operation regardless of vital signs, because hemodynamic "stability"
      does not reliably exclude significant hemorrhage. Vascular injury, subsequent
      hypotension, blood transfusion, and complicated postoperative course are common
      in this population.

PMID- 16103288
TI  - Glycolide copolymer staple-line reinforcement reduces staple site bleeding during
      laparoscopic gastric bypass: a prospective randomized trial.
AB  - HYPOTHESIS: The use of staple-line reinforcement sleeves during laparoscopic
      gastric bypass reduces staple-line bleeding, which may translate into a reduction
      in the rate of gastrointestinal hemorrhage. DESIGN: Prospective randomized trial.
      SETTING: University hospital. PATIENTS AND INTERVENTIONS: Thirty-four patients
      undergoing laparoscopic gastric bypass were randomly assigned to receive either
      no reinforcement (control group, n = 17) or reinforcement of the staple line with
      glycolic copolymer sleeves (treatment group, n = 17). MAIN OUTCOME MEASURES:
      Demographic data, the number of stapler loads used, the number of staple-line
      bleeding sites, the amount of blood loss, the length of time required to obtain
      hemostasis of the staple lines, operative time, intraoperative and postoperative
      complications, and serial hemoglobin levels. RESULTS: The mean number of stapler
      loads used was similar between groups. The mean number of staple-line bleeding
      sites was significantly fewer in the treatment group for division of gastric
      tissue (0.4 vs 2.5 bleeding sites), jejunal tissue (0.1 vs 0.6 bleeding site),
      and mesenteric tissue (0 vs 0.8 bleeding site). The mean blood loss was lower in
      the treatment group (84 vs 129 mL). Staple misfire occurred in 1 (0.7%) of 143
      stapler loads used in the treatment group compared with 0 (0%) of 138 stapler
      loads used in the control group. The time to obtain staple-line hemostasis was
      shorter in the treatment group (1.2 vs 10.1 minutes). The total operative time
      was similar between groups. There was no mortality or postoperative leaks. One
      patient in the control group had postoperative gastrointestinal hemorrhage
      requiring blood transfusion and reoperation. There was no significant difference
      in the mean hemoglobin level between groups on the first postoperative day.
      CONCLUSIONS: The use of glycolide copolymer staple-line reinforcement sleeves in
      patients undergoing laparoscopic gastric bypass is safe and significantly reduces
      staple-line bleeding sites and may reduce the incidence of gastrointestinal
      hemorrhage.

PMID- 16103289
TI  - Totally robotic Roux-en-Y gastric bypass.
AB  - HYPOTHESIS: We hypothesized that we could develop a safe and effective technique
      for performing a totally robotic laparoscopic Roux-en-Y gastric bypass procedure
      using the da Vinci surgical system. We anticipated that the learning curve for
      this totally robotic procedure could be shorter than the learning curve for
      standard laparoscopic bariatric surgery. DESIGN: Retrospective case comparison
      study. SETTING: Academic tertiary care center. PATIENTS: Consecutive samples of
      patients who met National Institutes of Health (NIH) criteria for morbid obesity
      and who completed the Stanford Bariatric Surgery Program evaluation process.
      INTERVENTION: A port placement and robot positioning scheme was developed so that
      the entire case could be performed robotically. The first 10 patients who
      underwent a totally robotic laparoscopic Roux-en-Y gastric bypass were compared
      with a retrospective sample of 10 patients who had undergone laparoscopic Roux-en
      Y gastric bypass surgery. MAIN OUTCOME MEASURES: Patient age, gender, body mass
      index (BMI), numbers of NIH-defined comorbidities, operative time, length of
      stay, and complications. RESULTS: No significant differences existed between the
      2 patient series with regard to age, gender, or BMI. The median surgical times
      were significantly lower for the robotic procedures (169 vs 208 minutes; P =
      .03), as was the ratio of procedure time to BMI (3.8 vs 5.0 minutes per BMI for
      the laparoscopic cases; P = .04). CONCLUSIONS: This study details the first
      report, to our knowledge, of a totally robotic laparoscopic Roux-en-Y gastric
      bypass and demonstrates the feasibility, safety, and potential superiority of
      such a procedure. In addition, the learning curve may be significantly shorter
      with the robotic procedure. Further experience is needed to understand the long
      term advantages and disadvantages of the totally robotic approach.

PMID- 16103290
TI  - Breast conserving surgery and accelerated partial breast irradiation using the
      MammoSite system: initial clinical experience.
AB  - HYPOTHESIS: Balloon catheter-based accelerated partial breast irradiation (APBI)
      may result in desirable short-term outcomes in patients undergoing breast
      conserving surgery. DESIGN: Prospective consecutive case series. SETTING:
      Tertiary multidisciplinary referral center. PATIENTS: Forty selected patients
      with invasive breast carcinoma undergoing breast conserving surgery and MammoSite
      device placement. INTERVENTIONS: Breast conserving surgery, sentinel and/or
      axillary node dissection, placement of the new balloon catheter applicator
      (MammoSite device), and APBI. MAIN OUTCOME MEASURES: Infection, early and late
      seroma, device explantation, time to initiating APBI, acute toxic effects on the
      skin, and cosmesis using the Harvard Scale. RESULTS: Thirty-nine patients
      underwent MammoSite device placement at the time of lumpectomy; 1 patient
      underwent percutaneous device placement after lumpectomy. Nineteen patients (49%)
      had drainage catheters placed in the breast cavity at the time of lumpectomy.
      Wound infection developed in 3 patients (8%). Five devices (12%) were explanted
      because of unfavorable final pathological findings or infection. The mean time to
      the start of APBI in patients who did not undergo simultaneous drain placement
      was 7.2 days (range, 5-12 days), compared with 5.1 days (range, 3-8 days) in
      patients who did (P = .008). With a mean follow-up of 13.3 months (range, 2-28
      months), patients completing APBI had limited toxic effects on the skin, with
      excellent or good cosmetic results in 39 patients (97%). CONCLUSIONS: Use of the
      MammoSite system in APBI has favorable short-term outcomes. Infection and
      radiation treatment delay are common and may warrant use of perioperative
      antibiotics and drain placement, respectively. A small number of patients who
      have device placement at the time of lumpectomy will require explantation because
      of unfavorable final pathological findings. Short-term outcomes of MammoSite
      brachytherapy support further studies comparing APBI with standard whole breast
      irradiation in patients undergoing breast conserving surgery.

PMID- 16103291
TI  - Role of thromboxane in producing hepatic injury during hepatic stress.
AB  - Hepatic injury after hepatic stress is caused by several mechanisms, including
      inflammatory reaction and microcirculatory disturbance. Levels of thromboxane, a
      vasoconstrictive eicosanoid, have been shown to increase in systemic circulation
      after different types of hepatic stress such as endotoxemia, hepatic ischemia
      reperfusion, hepatectomy, liver transplantation, hemorrhagic shock and
      resuscitation, hepatic cirrhosis, and alcoholic liver injury. The production of
      thromboxane from the liver is also enhanced under these stresses, which may act
      on the liver in an autocrine or a paracrine fashion. Kupffer cells, resident
      hepatic macrophages, may be a major source of stress-induced thromboxane,
      although other cell types in the liver such as sinusoidal endothelial cells and
      hepatocytes may also produce this eicosanoid. Thromboxane induces hepatic damage
      through vasoconstriction, platelet aggregation, induction of leukocyte adhesion,
      up-regulation of proinflammatory cytokines, and induction of other
      vasoconstrictor release. In this regard, administration of cyclooxygenase
      inhibitor, specific thromboxane synthase inhibitor, and specific thromboxane
      receptor antagonists has been shown to protect from severe hepatic injury
      elicited by these hepatic stresses. Furthermore, blockade of Kupffer cell
      function by administration of gadolinium chloride showed salutary effects in
      preventing hepatic damage in bile duct ligation models. This review article
      summarizes the recent knowledge of the role of thromboxane in various types of
      hepatic stress and the effects of thromboxane inhibitors in these models.

PMID- 16103292
TI  - Image of the month: angiosarcoma of the breast.

PMID- 16103293
TI  - Randomized trial of fixation vs nonfixation of mesh in total extraperitoneal
      inguinal hernioplasty.

PMID- 16103294
TI  - Anatomic resection of left liver segments.

PMID- 16103295
TI  - Going home.

PMID- 16103296
TI  - Corticosteroid response and supporting cell antibody in autoimmune hearing loss.
AB  - OBJECTIVE: To determine whether antibodies to supporting cells are associated
      with response to corticosteroids in patients with autoimmune sensorineural
      hearing loss. DESIGN: Prospective analysis of antibody to inner-ear antigens.
      SETTING: Collaborating otology practices in Pennsylvania, Michigan, and Indiana.
      PATIENTS: Sixty-three patients with rapidly progressive unilateral or bilateral
      sensorineural hearing loss of unknown cause suggestive of autoimmune
      sensorineural hearing loss. INTERVENTIONS: Pretreatment audiometry, serum
      analysis by Western blot (WB) and immunofluorescence (IF) tests, corticosteroid
      therapy, and follow-up audiometry. MAIN OUTCOME MEASURES: Antibody reactivity and
      audiogram changes were analyzed for association with response to treatment.
      RESULTS: More than half of the patients (37/63) had antibodies to both a 68- to
      72-kDa protein and to inner-ear supporting cells, 16 patients had positive
      results on one assay only, and 10 had negative results on both. Twenty-eight
      patients improved and 35 did not. The WB findings did not correlate with
      response. Of the WB-positive patients, 49% (21/43) improved, as did 35% (7/20) of
      the WB-negative patients (P = .30). In contrast, 53% (25/47) of IF-positive
      patients improved, compared with only 19% (3/16) in the IF-negative group (P =
      .02). Of those who improved, 89% (25/28) were IF positive. CONCLUSIONS: Antibody
      to an inner-ear supporting cell antigen was significantly associated with hearing
      improvement after corticosteroid therapy (relative rate, 2.8). Patients with IF
      positive serum are nearly 3 times more likely to experience improved hearing with
      corticosteroid treatment than those who are IF negative. Antibodies to inner-ear
      supporting cell antigen may have value in diagnosis and treatment of patients
      with autoimmune sensorineural hearing loss.

PMID- 16103297
TI  - Chronic dizziness and anxiety: effect of course of illness on treatment outcome.
AB  - OBJECTIVE: To investigate the hypothesis that the efficacy of selective serotonin
      reuptake inhibitors (SSRIs) for chronic subjective dizziness (CSD) and anxiety
      depends on the longitudinal pattern of the patients' symptoms. DESIGN:
      Prospective cohort study. SETTING: Tertiary care, multidisciplinary, balance
      center. PATIENTS: Eighty-eight consecutive patients treated with an SSRI for CSD
      and anxiety between 1998 and 2003. All patients were referred for evaluation of
      unremitting dizziness. They entered SSRI treatment after comprehensive
      neurotologic and psychiatric evaluations revealed a syndrome of CSD with
      accompanying anxiety. Patients were separated into 3 groups according to their
      longitudinal patterns of illness: (1) otogenic, defined as primary neurotologic
      conditions triggering secondary anxiety disorders; (2) psychogenic, defined as
      anxiety disorders alone causing dizziness; and (3) interactive, defined
      neurotologic conditions exacerbating preexisting anxiety. INTERVENTIONS: Patients
      with CSD were treated with an SSRI according to an established protocol for at
      least 8 weeks or until they proved intolerant to medication. MAIN OUTCOME
      MEASURES: Changes in dizziness and anxiety as measured by the Clinical Global
      Impressions-Improvement scale. RESULTS: Patients with the otogenic and
      psychogenic patterns of illness had a more complete response to SSRI treatment
      than did patients in the interactive group (P<.01). Rates of SSRI intolerance
      were similar for all 3 groups. CONCLUSIONS: Selective serotonin reuptake
      inhibitors are effective for patients with CSD and anxiety. However, patients
      with clinically significant anxiety predating neurotologic illness may require
      more intensive interventions.

PMID- 16103298
TI  - Detection of labyrinthine fistulas in human temporal bone by virtual endoscopy
      and density threshold variation on computed tomographic scan.
AB  - OBJECTIVE: To assess the sensitivity of the routine computed tomographic (CT)
      scan of the temporal bone coupled to a virtual endoscopy, with density threshold
      variation, in detecting small fistulas in human temporal bone specimens. DESIGN:
      Single-blind, before-after trial. SETTING: This study was carried out in a
      research laboratory in collaboration with a radiology department. PATIENTS: Five
      human adult temporal bone specimens were included. INTERVENTIONS: The fistulas
      were created with calibrated burrs (0.3, 0.5, and 0.8 mm) in the 3 semicircular
      canals and in the promontory of 3 temporal bones. Two other temporal bones served
      as controls. All bones underwent CT scan (1-mm section thickness) before and
      after dissection. Three-dimensional images were obtained from CT scan native
      axial views at different density reconstruction thresholds. The virtual endoscope
      was placed in the middle ear cavity looking to the inner ear wall. The threshold
      at which a bony defect appeared on virtual endoscopic images (opening threshold
      in Hounsfield units [H]) was noted for each location. MAIN OUTCOME MEASURES:
      Opening thresholds before and after dissection. RESULTS: On standard axial views,
      fistulas smaller than 0.5 mm were not visualized. By virtual endoscopy, all
      fistulas could be visualized. The opening threshold decreased after fistula
      creation in the semicircular canals (1244 +/- 50.5 H [n = 36] vs 778 +/- 52.4 H
      [n = 34]; P<.001; 1-way analysis of variance and Dunnett multiple comparisons
      posttest) and in the promontory (1541 +/- 37.8 H [n = 12] vs 1334 +/- 35.1 H [n =
      8]; P<.001). The opening thresholds in the control specimens remained unchanged
      after dissection. CONCLUSION: Virtual endoscopy with variation of reconstruction
      threshold allows the detection of small labyrinthine fistulas with diameters of
      0.3 mm or smaller.

PMID- 16103299
TI  - Preoperative evaluation of ossicular chain abnormality in patients with
      conductive deafness without perforation of the tympanic membrane.
AB  - OBJECTIVE: To evaluate the usefulness of pure-tone audiometry, tympanometry, and
      liquid and acoustic reflex (AR) tests in the differential diagnosis of ossicular
      fixation and discontinuity. DESIGN: A prospective clinical trial. SETTING:
      Tertiary referral center. PATIENTS: Thirty-nine patients (46 ears) undergoing
      operations at University of Tsukuba Hospital, Tsukuba, Japan, from 1990 through
      2003 for conductive deafness without perforation of the tympanic membrane.
      Clinical examinations for the preoperative diagnosis included pure-tone
      audiometry, tympanometry, and liquid and AR tests. We compared the preoperative
      diagnosis with the surgical findings. RESULTS: Although neither pure-tone
      audiometry nor tympanometry contributed to the differential diagnosis of
      ossicular chain abnormality, liquid and AR test results showed a significant
      difference between fixation and discontinuity of the ossicular chain. With the
      liquid test, bone conduction at lower frequencies was improved by filling the
      external auditory canal with water at lower frequencies in cases of ossicular
      fixation. In contrast to the findings observed in ossicular fixation, no
      improvement of the threshold of bone conduction was recognized at any frequency
      in the ears with ossicular discontinuity. In ipsilaterally stimulated AR, the
      reversed pattern was the most marked at 2000 and 500 Hz in ossicular fixation and
      discontinuity, respectively. CONCLUSION: Liquid and AR tests are reliable
      examinations for the differential diagnosis of ossicular fixation and
      discontinuity.

PMID- 16103300
TI  - Prevention of anterior glottic stenosis after bilateral vocal fold stripping with
      mitomycin C.
AB  - OBJECTIVE: To examine the effects of immediate application of topical mitomycin C
      (MMC) on the prevention of anterior glottic stenosis (AGS) after microsurgical
      stripping of both vocal folds, including the anterior commissure, in a canine
      model. DESIGN: Prospective randomized experimental study. INTERVENTIONS: Twelve
      canine larynges were injured by a stripping procedure of both entire membranous
      vocal folds. The dogs were randomly divided into 2 groups for treatment with 1.0
      mg/mL of MMC or with isotonic sodium chloride solution (control) for 5 minutes
      immediately after surgery. Three and 6 weeks after surgery, the glottic webs were
      lysed and repeatedly treated with MMC or isotonic sodium chloride solution. The
      glottic wound healing and AGS formation were examined every week. Ten weeks after
      the initial surgery, all larynges were collected and examined histologically.
      RESULTS: The stripping procedure induced AGS, affecting 58% to 86% (mean, 72%) of
      the length from the anterior commissure to the vocal process in the control
      group. The application of MMC at the time of initial surgery significantly
      lowered the incidence and extent of the web formation (P = .004). The AGS lesions
      were resolved by web lysis and treatment with MMC, without significant local
      adverse effects. Histological staining for collagen and elastin revealed that MMC
      treatment did not induce excessive fibrotic or atrophic changes in the lamina
      propria of the vocal folds. CONCLUSION: Bilateral stripping of the membranous
      vocal folds induces significant AGS, which can be minimized by use of MMC at
      initial surgery.

PMID- 16103301
TI  - Laryngeal aerodynamics after vocal fold augmentation with autologous fat vs
      thyroplasty in the same patient.
AB  - OBJECTIVE: To analyze laryngeal aerodynamics in the same patient in 4 different
      circumstances: before the onset of unilateral vocal fold paralysis (UVFP), after
      the onset of UVFP, and after 2 types of surgical vocal fold medialization
      techniques to compare the results of surgery with the measurements made in that
      same patient when his larynx was healthy (before paralysis). DESIGN: Prospective
      self-paired study of 1 male patient. Measurements were taken before iatrogenic
      UVFP (of the patient's healthy larynx), 1 week after the onset of iatrogenic UVFP
      (thoracic surgery), 3 days after vocal fold medialization with autologous fat,
      and 2 months after polytetrafluoroethylene thyroplasty. SETTING: University
      hospital. MAIN OUTCOME MEASURE: Phonatory airflow and intraoral pressure.
      RESULTS: Airflow and intraoral pressure increased after the onset of UVFP.
      Airflow decreased to preparalytic values after both types of vocal fold
      medialization. Intraoral pressure decreased after fat injection but increased
      after thyroplasty, despite the favorable effects of this treatment on laryngeal
      resistance and vocal efficiency compared with preparalytic values. CONCLUSIONS:
      Our study demonstrates the variability of intraoral pressure as an indirect
      measure of subglottal pressure after vocal fold medialization in UVFP, due to as
      yet unknown factors. Phonatory airflow, laryngeal resistance, and vocal
      efficiency seem to be more reliable indicators of aerodynamic results after vocal
      fold medialization.

PMID- 16103302
TI  - Beta-catenin and cyclin D1 in mucoepidermoid carcinoma of variable histologic
      grades.
AB  - OBJECTIVE: To analyze the expression of beta-catenin and cyclin D1 in
      mucoepidermoid carcinoma (MEC) of variable histologic grades to establish a
      correlation between the expression of these proteins and the different
      histopathologic grades of this neoplasia. DESIGN: Immunohistochemical analysis of
      MEC. SETTING: Pathological Anatomy Service, Discipline of Oral Pathology,
      Department of Dentistry, Federal University of Rio Grande do Norte, Natal,
      Brazil. PATIENTS: Fifteen cases of MEC, graded and categorized according to
      criteria reported in the literature into 5 tumors with a low grade of malignancy,
      4 with an intermediate grade, and 6 with a high grade. MAIN OUTCOME MEASURES:
      Labeling patterns of beta-catenin and cyclin D1. RESULTS: No significant
      difference in beta-catenin labeling patterns was observed between low- and
      intermediate-grade tumors or between low- and high-grade tumors (P = .60 and P =
      .06, respectively; Fisher exact test), despite a strong tendency toward a
      difference in the latter. In contrast, a significant difference was noted between
      intermediate- and high-grade tumors (P = .03). For cyclin D1, no labeling was
      observed in any high-grade cases, and only 3 cases showed overexpression of this
      protein. Comparison of the labeling patterns among the different histologic
      grades revealed no significant difference. CONCLUSIONS: The reduced expression of
      beta-catenin observed in all high-grade MECs is probably due to the loss of its
      adhesion function, which confers a greater invasive potential to these tumors.
      The overexpression of cyclin D1 observed in only 3 MEC cases suggests that this
      protein does not participate in the etiopathogenesis of these tumors, which
      implies that other genes are likely responsible.

PMID- 16103303
TI  - Differential expression of epidermal growth factor receptor, c-Met, and HER2/neu
      in chordoma compared with 17 other malignancies.
AB  - OBJECTIVE: To examine the expression of c-Met, c-Erb-b2 (HER2/neu), and epidermal
      growth factor (EGFR) in a cohort of 12 chordomas, based on the current and future
      availability of targeted molecular inhibitors. DESIGN: Protein expression levels
      were analyzed by immunohistochemical analysis from archival tissue using
      multitumored tissue microarray and by Spearman rank correlation test. SETTING:
      Tertiary care facility. SUBJECTS: We assembled the cohort of 12 chordomas from
      patients treated at the Yale-New Haven Hospital from 1986 to 2003 and compared
      them with 51 other tumors from 17 assorted solid tissue tumor types along with 1
      sample of healthy tissue from each site. MAIN OUTCOME MEASURE: The expression of
      c-Met, HER2/neu, and EGFR. RESULTS: Most chordomas displayed strong expression of
      EGFR and c-Met, whereas a variable level of expression of HER2/neu was seen. In
      addition, we noted a strong correlation between EGFR and c-Met expression,
      especially for primary chordomas (P = .006). CONCLUSIONS: Chordomas, like many
      other solid-tissue tumors, express HER2/neu, EGFR, and the hepatocyte growth
      factor/scatter factor receptor c-Met. Most chordomas had strong expression of
      both the hepatocyte growth factor/scatter factor receptor and EGFR. Inhibitors to
      EGFR are already in clinical use for other solid-tissue tumors and represent a
      potentially viable experimental treatment option for refractory chordoma. Further
      studies are required to investigate these findings.

PMID- 16103304
TI  - Management of head and neck plexiform neurofibromas in pediatric patients with
      neurofibromatosis type 1.
AB  - OBJECTIVES: To identify presenting symptoms, growth patterns, and outcomes of
      head and neck plexiform neurofibromas (PNs) in children with neurofibromatosis
      type 1 (NF-1); to determine which patients may benefit most from operative
      intervention in terms of duration of disease-free progression, perioperative
      morbidity, identification of malignancy, and symptom relief. DESIGN: A
      retrospective review of 39 pediatric patients with NF-1 who had PNs of the head
      and neck managed at a single tertiary referral center. RESULTS: Thirty-nine
      patients had 49 head and neck PNs, 11 small (<or=5 cm) and 38 massive (>5 cm
      and/or involving multiple deep neck sites). Thirty-nine surgical procedures were
      performed on 18 of 35 patients with massive disease, and 4 procedures were
      performed on 4 of 11 patients with small tumors. Tumors recurred in 1 (25%) of 4
      patients with small tumors and in 18 (100%) of 18 patients with massive tumors (P
      = .001; mean time to regrowth, 3.1 years.) CONCLUSIONS: Size and location of PN
      tumors most influenced presentation of clinical symptoms. Complete tumor
      resection was possible only in patients with small PNs. Patients with PNs of the
      head and neck were more likely to benefit from surgery if the indications were to
      (1) exclude malignancy in a rapidly enlarging mass; (2) provide relief from
      neurogenic pain or motor weakness; (3) improve symptoms caused by airway
      compression; or (4) enhance cosmesis in those with disfiguring disease.

PMID- 16103305
TI  - Internet use by parents of children undergoing outpatient otolaryngology
      procedures.
AB  - OBJECTIVES: (1) To determine the prevalence of Internet medical information
      searches by parents prior to their child's surgical procedure, and (2) to
      evaluate whether Internet-based health information influences parents' medical
      decisions on behalf of their children. DESIGN: A questionnaire designed to gather
      information regarding preoperative use of the Internet by parents of children who
      were scheduled to undergo outpatient otolaryngology procedures. Parents were
      asked to respond to questions regarding Internet searches for information
      specific to their child's diagnosis and anticipated surgical procedure. SETTING:
      Tertiary care pediatric hospital. RESULTS: Internet access was available to 83%
      of respondents. Of those parents with Internet access, 48% searched the Internet
      for information regarding their child's diagnosis and surgical procedure. Of
      those who searched the Internet, 93% said they found information that was both
      understandable and helpful. More important, 84% of parents using the Internet
      said the information influenced or somewhat influenced the medical decisions they
      made on behalf of their child. Only 43% of parents discussed the information they
      found on the Internet with their child's surgeon. CONCLUSIONS: Approximately 50%
      of the parents in our study with Internet access used it to find medical
      information prior to their child's surgery. Parents who used the Internet found
      the information helpful and influential, although physicians remain the most
      important source of information that guides a parent or patient in their medical
      decision making. Ideally, surgeons would direct parents or patients to a few
      trusted Internet sites and be prepared to discuss this information.

PMID- 16103306
TI  - The differences of blowout fracture of the inferior orbital wall between children
      and adults.
AB  - OBJECTIVES: To review the clinical features and recovery period of patients with
      blowout fractures of the inferior orbital wall treated surgically and to examine
      the differences between children and adults. DESIGN: A retrospective study.
      SETTING: Department of Otorhinolaryngology, Maryknoll General Hospital, Busan,
      Korea. Patients Medical records of 70 patients were reviewed: 16 patients were
      children (aged <16 years) and 54 were adults (aged >or=17 years). MAIN OUTCOME
      MEASURES: Symptoms and fracture patterns were compared between both groups in all
      subjects, and the recovery period relative to the timing of surgery after the
      trauma was compared in subjects who complained of diplopia or extraocular
      limitation. RESULTS: Serious periorbital edema was noted in 43 adults (80%) and 4
      children (25%), diplopia in 27 adults (50%) and 16 children (100%), and
      extraocular muscle limitation in 23 adults (43%) and 13 children (81%). Trapdoor
      fractures were frequent in the children group (n = 13; 81%), whereas 30 patients
      (56%) had open-door fractures in the adult group. In the children group, no
      differences in the recovery period relative to the timing of surgery was noted
      when all types of orbital fractures were considered. However, among the 13
      children with trapdoor fractures, the recovery period was significantly shorter
      in those who underwent surgery 1 to 5 days after the trauma compared with those
      who underwent surgery after 6 to 14 days and 15 days or longer. In adults, the
      recovery period of those who underwent surgery 1 to 5 days and 6 to 14 days after
      the trauma were significantly shorter compared with those who underwent surgery
      after 15 days or longer. CONCLUSIONS: Diplopia, extraocular muscle limitation,
      and trapdoor fractures were more frequent in children than in adult patients.
      After trauma, surgical intervention might be required within 5 days in children
      with trapdoor fracture vs within 2 weeks in adults.

PMID- 16103307
TI  - How computed tomography may be useful in pulsatile tinnitus with normal otoscopic
      findings.

PMID- 16103308
TI  - Intratympanic steroid perfusion for sudden sensorineural hearing loss.

PMID- 16103309
TI  - Diagnostic and management dilemma of sudden hearing loss.

PMID- 16103310
TI  - Broadening the spectrum of treatment options for SNHL.

PMID- 16103311
TI  - Pathology quiz case: mandibular metastasis of hepatocellular carcinoma.

PMID- 16103313
TI  - Radiology quiz case 1: rhinocerebral mucormycosis with cavernous sinus
      thrombosis.

PMID- 16103314
TI  - Radiology quiz case 2: orbital pseudotumor.

PMID- 16103315
TI  - Radiology quiz case 3: laryngeal tuberculosis.

PMID- 16103316
TI  - Radiology quiz case 4: primary atrophic rhinitis, or ozena.

PMID- 16103321
TI  - Use of a conchal bowl flap for repair of the earlobe.

PMID- 16103322
TI  - Randomized controlled trial testing the impact of high-protection sunscreens on
      sun-exposure behavior.
AB  - OBJECTIVE: High-protection sunscreens have been suspected to prompt people to
      increase sun exposure, and thus to increase skin cancer risk. We tested the
      influence of both the actual protection (sun protection factor [SPF]) and the
      information about protection (label) on sun-exposure behavior. DESIGN: Randomized
      controlled trial. SETTING: Four French seaside resorts during summer 2001.
      PARTICIPANTS: A total of 367 healthy subjects during their 1-week holiday.
      Outcome was assessable in 98% of them. INTERVENTION: Subjects were offered free
      sunscreens, with randomization into the following study arms: (1) SPF 40 labeled
      as "high protection"; (2) SPF 40 labeled as "basic protection"; and (3) SPF 12
      labeled as "basic protection." Arm 4, ie, SPF 12 labeled as "high protection,"
      was not implemented for ethical reasons. Subjects were not aware of the real
      target of the study and were blinded to the SPF value. MAIN OUTCOME MEASURE:
      Duration of sunbathing exposure during 1 week. Secondary outcomes were occurrence
      of sunburns and amount of sunscreen used. Influences of SPF and label were
      assessed separately. RESULTS: Compared with the low-SPF group, the high-SPF group
      did not have longer sunbathing exposure (12.9 +/- 7.2 h/wk for high SPF vs 14.6
      +/- 6.7 h/wk for low SPF; P = .06), experienced fewer sunburns (14% vs 24%; P =
      .049), and used less sunscreen (median, 30 g vs 109 g; P<.001). The label "high
      protection" or "basic protection" had no influence on these end points.
      CONCLUSIONS: In this adult population, higher SPF had no influence on duration of
      sun exposure and offered better protection against sunburns. Although higher SPF
      may increase sun exposure duration in specific populations, this effect cannot be
      viewed as a universal side effect of high-SPF sunscreens.

PMID- 16103323
TI  - Compliance with youth access regulations for indoor UV tanning.
AB  - OBJECTIVES: To describe youth access to indoor UV tanning and youth discount
      pricing incentives in 4 states with different age restrictions: Colorado (no age
      restrictions), Texas (age 13 years), Illinois (age 14 years), and Wisconsin (age
      16 years). DESIGN: Cross-sectional telephone survey conducted in October 2003
      using a standardized script to assess the practices of randomly selected UV
      tanning operators. PARTICIPANTS: Randomly selected licensed indoor UV tanning
      facility operators in Colorado, Texas, Illinois, and Wisconsin. MAIN OUTCOME
      MEASURES: Number of facilities (1) complying with indoor UV tanning minimum age
      regulations for a 12-year-old potential patron and a 15-year-old potential patron
      and (2) offering youth discounts. RESULTS: For a 12-year-old potential patron,
      62% of facilities in states with minimum age restrictions prohibiting 12-year
      olds had an operator report that they would not permit indoor tanning (Texas,
      23%; Illinois, 74%; and Wisconsin, 89%) compared with 18% in Colorado, a state
      without youth access regulations. For a 15-year-old patron, most facilities in
      Wisconsin, the only state with a minimum age restriction for 15-year-olds,
      prohibited access (77%). Overall, 15% of operators offered youth discounts:
      Texas, 23%; Illinois, 14%; Wisconsin, 11%; and Colorado, 11%. CONCLUSIONS:
      Tanning facilities in 4 states offered price incentives directed at youths. State
      youth access regulations were associated with decreased youth access to indoor
      tanning. High compliance levels in states with long-standing youth access
      regulations (Illinois and Wisconsin) demonstrate the potential for successful
      tanning industry youth access regulation.

PMID- 16103324
TI  - UV light tanning as a type of substance-related disorder.
AB  - OBJECTIVE: To better understand the complex motivations involved with UV light
      (UVL) tanning behavior. DESIGN: Two written instruments, the CAGE (Cut down,
      Annoyed, Guilty, Eye-opener) Questionnaire, used to screen for alcohol abuse or
      dependence, and the American Psychiatric Association Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria
      for substance-related disorders, were modified to evaluate subjects for a
      substance-related disorder involving UVL tanning. SETTING: Galveston Island
      beach. Subjects A total of 145 beach-goers. MAIN OUTCOME MEASURES: Positive
      findings from the 2 evaluation instruments. RESULTS: Of the 145 subjects, 38
      (26%) met the modified CAGE criteria, and 77 (53%) met the modified DSM-IV-TR
      diagnostic criteria for a substance-related disorder with regard to UVL and
      related sun tanning. The results from both instruments were significantly
      associated (P = .03). CONCLUSIONS: Individuals who chronically and repetitively
      expose themselves to UVL to tan may have a novel type of UVL substance-related
      disorder.

PMID- 16103325
TI  - Sunscreen use related to UV exposure, age, sex, and occupation based on personal
      dosimeter readings and sun-exposure behavior diaries.
AB  - OBJECTIVES: To examine during what behaviors people apply sunscreen and to assess
      the relationship to UV exposure monitored by personal dosimetry and diaries.
      DESIGN: Open prospective observational study. SETTING: University hospital.
      PARTICIPANTS: A convenience sample of 340 Danish volunteers: children,
      adolescents, indoor workers, sun worshippers, golfers, and gardeners (age range,
      4-68 years). Intervention Subjects recorded sunscreen use and sun-exposure
      behavior in diaries and carried personal, electronic UV dosimeters, measuring
      time-stamped UV doses continuously, during a median of 119 days covering 346 sun
      years (1 sun-year equals 1 subject participating during 1 summer season). MAIN
      OUTCOME MEASURES: Associations between sunscreen use and age, sex, skin type,
      occupation, sunburn, UV exposure doses, and behavior; and adequate application
      density and sun protection factor required to prevent sunburn. RESULTS: There
      were great variations in sunscreen use, which was highly correlated with risk
      behavior (sunbathing or exposing the upper body) (r = 0.39; P<.001). Sunscreens
      were used on a median of 5 days per sun-year (range, 1 day for gardeners to 16
      days for sun worshippers). Ten percent of females and 41% of males never used
      sunscreens. Females used sunscreens more but also had more unprotected risk
      behavior than males (8 days vs 4 days; P<.001). Sunscreen use was not correlated
      with age, and children had as much unprotected risk behavior as adults.
      Sunscreens were used on 86% of the days with risk behavior in southern Europe vs
      20% in northern Europe (P<.001). The UV doses were significantly higher on days
      with sunscreen (P< or = .03) and on sunburn days (P<.001). The median sun
      protection factor was 10.5. The sun-protecting effect corresponded to an
      application density of 0.5 mg/cm2. CONCLUSION: Days with sunscreen correlated not
      with days without risk behavior, but with days "sunbathing with the intention to
      tan," indicating that sunscreens were used as tanning aids to avoid sunburn.

PMID- 16103326
TI  - Sunscreen use before and after transplantation and assessment of risk factors
      associated with skin cancer development in renal transplant recipients.
AB  - OBJECTIVE: To determine the degree of compliance with sunscreen use among renal
      transplant recipients before and after transplantation and to determine risk
      factors associated with skin carcinogenesis. DESIGN: Single-observer study with
      structured interview using a standardized questionnaire. Medical records and
      histology reports were examined for details of prior skin cancer. Cox
      proportional hazards regression was used for analysis of risk factors for
      developing skin cancer after transplantation. SETTING: Patients attending
      Beaumont Hospital, the national renal transplantation center in Dublin, Ireland.
      PATIENTS: The study population comprised 270 patients (182 male and 88 female).
      MAIN OUTCOME MEASURES: Patients' use of sunscreens before and after
      transplantation relative to known skin cancer risk factors and subsequent skin
      carcinogenesis. RESULTS: Prior to transplantation, 68.5% of patients never
      applied sunscreen on a sunny day compared with 25.9% after transplantation.
      Patients 50 years or younger were more likely to always apply sunscreen both
      before and after transplantation (P = .01), as were female patients prior to
      transplantation (P = .02). Those patients who participated in an outdoor
      recreation were more likely to subsequently develop nonmelanoma skin cancer (P =
      .04), as were those older than 50 years (P<.001) and those with a history of 2 or
      more painful sunburns (P = .03). CONCLUSIONS: Transplant recipients are poorly
      compliant with the use of sunscreens both before and after transplantation.
      Compliance is poorest in those groups at higher risk of nonmelanoma skin cancer.

PMID- 16103328
TI  - Safety and efficacy of 5% imiquimod cream for the treatment of skin dysplasia in
      high-risk renal transplant recipients: randomized, double-blind, placebo
      controlled trial.
AB  - OBJECTIVE: To evaluate the safety and efficacy of 5% imiquimod cream for
      cutaneous dysplasia in high-risk renal transplant recipients. DESIGN: A
      randomized, blinded, placebo-controlled study comparing treated with control
      skin. SETTING: A specialist organ transplant dermatology clinic. PATIENTS: Twenty
      one high-risk patients with skin cancer with comparable areas of clinically
      atypical skin on dorsal hands or forearms. INTERVENTIONS: Imiquimod or placebo
      (randomly assigned) applied 3 times a week for 16 weeks to 1 dorsal hand or
      forearm, with 8 months of follow-up. At week 16, biopsy samples were collected
      from pre-assigned sites in the treatment and control areas and were examined for
      dysplasia. MAIN OUTCOME MEASURES: The proportion of patients showing reduced
      numbers of viral and keratotic lesions and reduced histological severity of
      dysplasia in the treatment vs control areas at week 16, serum creatinine levels,
      and tumors developing in the study sites. RESULTS: Fourteen patients receiving
      imiquimod and 6 receiving placebo completed the study. Seven patients using
      imiquimod (1 taking placebo) had reduced skin atypia, 7 using imiquimod (none
      taking placebo) had reduced viral warts, and 5 using imiquimod (1 taking placebo)
      showed less dysplasia histologically. In 1 year, fewer squamous skin tumors arose
      in imiquimod-treated skin than in control areas. Renal function was not adversely
      affected. CONCLUSIONS: Topical 5% imiquimod cream seems to be safe on skin areas
      up to 60 cm2 in renal transplant recipients. It may be effective in reducing
      cutaneous dysplasia and the frequency of squamous tumors developing in high-risk
      patients. Larger studies are required to confirm these results.

PMID- 16103329
TI  - Incidence of new and changed nevi and melanomas detected using baseline images
      and dermoscopy in patients at high risk for melanoma.
AB  - OBJECTIVE: To determine the incidence of new, changed, and regressed nevi and
      melanomas in a cohort of patients at high risk for melanoma using baseline total
      body photography and dermatoscopy. DESIGN: Cohort study of patients at high risk
      for melanoma who underwent baseline cutaneous photography between January 1,
      1992, and December 31, 1997, and had at least 1 follow-up visit by December 31,
      1998. SETTING: Private practice rooms of 1 dermatologist in conjunction with a
      public hospital-based, multidisciplinary melanoma clinic in Victoria, Australia.
      PATIENTS: A total of 309 patients who had at least 1 of the following risk
      factors for melanoma: personal history, family history, 100 or more nevi, or 4 or
      more dysplastic nevi. MAIN OUTCOME MEASURES: Number of new, changed, and
      regressed nevi and melanomas detected and excised during the study interval.
      RESULTS: The incidence of new, changed, and regressed nevi decreased with
      increasing age (P<.001), whereas the incidence of melanomas increased (P = .05).
      The number of dysplastic nevi at baseline was positively associated with the
      incidence of changed nevi (P<.001) and melanomas (P = .03). The use of baseline
      photography and dermatoscopy was associated with low biopsy rates and early
      detection of melanomas. The development of melanoma in association with a
      preexisting nevus was not directly correlated with a change in a preexisting
      lesion monitored by baseline photography. CONCLUSIONS: Nevi are dynamic, and only
      a small percentage of all new and changed melanocytic lesions are melanomas.
      Patients younger than 50 years had a lower incidence of melanomas and a higher
      rate of new, changed, and regressed nevi when compared with patients older than
      50 years. A new or changed pigmented lesion is more likely to be a melanoma in
      patients older than 50 years.

PMID- 16103330
TI  - Comparative performance of 4 dermoscopic algorithms by nonexperts for the
      diagnosis of melanocytic lesions.
AB  - OBJECTIVE: To assess 4 dermoscopy methods in a nonexpert setting. DESIGN: Sixty
      one medical practitioners, mainly primary care physicians in Australia, were
      trained in 4 dermoscopy algorithms. Participants then assessed macroscopic and
      dermoscopic images of 40 melanocytic skin lesions. Each of the dermoscopic images
      was assessed with pattern analysis, the 7-point checklist, the ABCD rule, and the
      Menzies method. RESULTS: The Menzies method showed the highest sensitivity,
      84.6%, for the diagnosis of melanoma, followed by the 7-point checklist (81.4%),
      the ABCD rule (77.5%), pattern analysis (68.4%), and assessment of a macroscopic
      image (60.9%). Pattern analysis and assessment of the macroscopic image showed
      the highest specificity, 85.3% and 85.4%, respectively. The ABCD rule showed a
      specificity of 80.4%; the Menzies method, 77.7%; and the 7-point checklist, 73%.
      The Menzies method had a diagnostic accuracy of 81.1%; the ABCD rule, 79.0%; the
      7-point checklist, 77.2%; pattern analysis, 76.8%; and clinical assessment,
      73.2%. CONCLUSIONS: All algorithms performed well in the hands of relatively
      inexpert practitioners who had undertaken self-guided training provided on
      compact disc. The Menzies method showed the highest diagnostic accuracy and
      sensitivity for melanoma diagnosis and was preferred by study participants.

PMID- 16103331
TI  - Sentinel lymph node biopsy for cutaneous melanoma: the Stanford experience, 1997
      2004.
AB  - OBJECTIVE: To review sentinel lymph node (SLN) data from Stanford University
      Medical Center from January 1, 1997, to January 1, 2004, including rates of SLN
      positivity according to 2002 American Joint Committee on Cancer (AJCC) tumor
      classification, relation to other clinical and pathologic prognostic factors, and
      rates and sites of melanoma recurrence. DESIGN: Retrospective case series.
      SETTING: Stanford University Medical Center and Stanford melanoma clinics.
      PATIENTS: A total of 274 consecutive patients with primary melanoma who underwent
      SLN biopsy (SLNB) between January 1, 1997, and January 1, 2004, or who were
      referred to the Stanford melanoma clinics after SLNB and were followed up through
      March 2005. INTERVENTIONS: All patients underwent standard wide local excision of
      their primary tumors and SLNB with intradermal injection of isosulfan blue dye
      and/or technetium sulfur colloid. MAIN OUTCOME MEASURE: Rates of SLN positivity
      per 2002 AJCC tumor classification, relation to other clinical and pathologic
      prognostic factors, and rates and sites of melanoma recurrence in node-negative
      and node-positive patients. RESULTS: Positive SLNs were detected in 39 (15%) of
      260 cases, including 0 (0%) of 45 for cutaneous melanomas 1.0 mm thick or less
      (T1), 21 (18%) of 115 for melanomas 1.01 to 2.0 mm thick (T2), 12 (19%) of 64 for
      melanomas 2.01 to 4.0 mm thick (T3), and 5 (16%) of 32 for melanomas thicker than
      4.0 mm (T4). Median Breslow depths were 1.89 mm for SLN-positive biopsy specimens
      and 1.50 mm for SLN-negative biopsy specimens (P = .07). The recurrence rate was
      46% among SLN-positive patients, with a median time to recurrence of 8 months.
      Bivariate analysis revealed SLN positivity to be associated with AJCC tumor
      classification (P = .02), location on the trunk (P = .03), and presence of
      ulceration (P = .03). By multivariate logistic regression, ulceration (P = .01)
      was predictive of SLN positivity, whereas SLN status (P< .001), ulceration (P =
      .02), and location (P = .03) were predictive of recurrent disease. CONCLUSION:
      Data from the past 8 years confirm the accuracy and prognostic value of SLNB in
      cutaneous melanoma and the low rate of regional nodal recurrence for SLN-negative
      patients.

PMID- 16103332
TI  - Sunscreen, sun protection, and our many failures.

PMID- 16103333
TI  - Skin cancer risk behaviors: a conceptual framework for complex behavioral change.

PMID- 16103334
TI  - ABCDE--an evolving concept in the early detection of melanoma.

PMID- 16103336
TI  - Dehisced wound in a heart transplant recipient.

PMID- 16103337
TI  - Multinodular plaque in a young adult.

PMID- 16103338
TI  - Acquired fusiform swelling of the fingers.

PMID- 16103339
TI  - Fever and necrotic nodules on the extremities.

PMID- 16103340
TI  - Safe in the sun: low prevalence of sunburns and a high use of sun protection
      measures in Bavarian preschool children.

PMID- 16103341
TI  - Children with red hair have more freckles but fewer melanocytic nevi: results
      from a cohort study of 280 three-year-olds.

PMID- 16103342
TI  - A preliminary evaluation of polyvinyl chloride film use in dermoscopic analysis
      of mucosal areas.

PMID- 16103343
TI  - An additional dermoscopic feature of tungiasis.

PMID- 16103344
TI  - Thin melanoma of the vulva: a clinical, dermoscopic-pathologic case study.

PMID- 16103345
TI  - Site misclassification of melanomas in the shoulder region: an issue not to be
      "shrugged at"?

PMID- 16103346
TI  - Cutaneous manifestations of a catheter-related thrombus.

PMID- 16103347
TI  - Leg ulcer and Paget disease of the bone.

PMID- 16103348
TI  - Association of cutaneous necrotizing eosinophilic vasculitis and deep vein
      thrombosis in hypereosinophilic syndrome.

PMID- 16103349
TI  - Sterile neonatal pustulosis associated with transient myeloproliferative disorder
      in twins.

PMID- 16103350
TI  - Dermoscopy of pigmented Spitz and Reed nevi: the starburst pattern.

PMID- 16103351
TI  - Ancestral antibiotic resistance in Mycobacterium tuberculosis.
AB  - Chemotherapeutic options to treat tuberculosis are severely restricted by the
      intrinsic resistance of Mycobacterium tuberculosis to the majority of clinically
      applied antibiotics. Such resistance is partially provided by the low
      permeability of their unique cell envelope. Here we describe a complementary
      system that coordinates resistance to drugs that have penetrated the envelope,
      allowing mycobacteria to tolerate diverse classes of antibiotics that inhibit
      cytoplasmic targets. This system depends on whiB7, a gene that pathogenic
      Mycobacterium shares with Streptomyces, a phylogenetically related genus known as
      the source of diverse antibiotics. In M. tuberculosis, whiB7 is induced by
      subinhibitory concentrations of antibiotics (erythromycin, tetracycline, and
      streptomycin) and whiB7 null mutants (Streptomyces and Mycobacterium) are
      hypersusceptible to antibiotics in vitro. M. tuberculosis is also antibiotic
      sensitive within a monocyte model system. In addition to antibiotics, whiB7 is
      induced by exposure to fatty acids that pathogenic Mycobacterium species may
      accumulate internally or encounter within eukaryotic hosts during infection. Gene
      expression profiling analyses demonstrate that whiB7 transcription determines
      drug resistance by activating expression of a regulon including genes involved in
      ribosomal protection and antibiotic efflux. Components of the whiB7 system may
      serve as attractive targets for the identification of inhibitors that render M.
      tuberculosis or multidrug-resistant derivatives more antibiotic-sensitive.

PMID- 16103352
TI  - Cyclophilin D is a component of mitochondrial permeability transition and
      mediates neuronal cell death after focal cerebral ischemia.
AB  - Mitochondrial permeability transition (PT) is a phenomenon induced by high levels
      of matrix calcium and is characterized by the opening of the PT pore (PTP).
      Activation of the PTP results in loss of mitochondrial membrane potential,
      expansion of the matrix, and rupture of the mitochondrial outer membrane.
      Consequently, PT has been implicated in both apoptotic and necrotic cell death.
      Cyclophilin D (CypD) appears to be a critical component of the PTP. To
      investigate the role of CypD in cell death, we created a CypD-deficient mouse. In
      vitro, CypD-deficient mitochondria showed an increased capacity to retain calcium
      and were no longer susceptible to PT induced by the addition of calcium. CypD
      deficient primary mouse embryonic fibroblasts (MEFs) were as susceptible to
      classical apoptotic stimuli as the WT, suggesting that CypD is not a central
      component of cell death in response to these specific death stimuli. However,
      CypD-deficient MEFs were significantly less susceptible than their WT
      counterparts to cell death induced by hydrogen peroxide, implicating CypD in
      oxidative stress-induced cell death. Importantly, CypD-deficient mice displayed a
      dramatic reduction in brain infarct size after acute middle cerebral artery
      occlusion and reperfusion, strongly supporting an essential role for CypD in an
      ischemic injury model in which calcium overload and oxidative stress have been
      implicated.

PMID- 16103353
TI  - Calcineurin cleavage is triggered by elevated intraocular pressure, and
      calcineurin inhibition blocks retinal ganglion cell death in experimental
      glaucoma.
AB  - Increased intraocular pressure (IOP) leads, by an unknown mechanism, to apoptotic
      retinal ganglion cell (RGC) death in glaucoma. We now report cleavage of the
      autoinhibitory domain of the protein phosphatase calcineurin (CaN) in two rodent
      models of increased IOP. Cleaved CaN was not detected in rat or mouse eyes with
      normal IOP. In in vitro systems, this constitutively active cleaved form of CaN
      has been reported to lead to apoptosis via dephosphorylation of the proapoptotic
      Bcl-2 family member, Bad. In a rat model of glaucoma, we similarly detect
      increased Bad dephosphorylation, increased cytoplasmic cytochrome c (cyt c), and
      RGC death. Oral treatment of rats with increased IOP with the CaN inhibitor FK506
      led to a reduction in Bad dephosphorylation and cyt c release. In accord with
      these biochemical results, we observed a marked increase in both RGC survival and
      optic nerve preservation. These data are consistent with a CaN-mediated mechanism
      of increased IOP toxicity. CaN cleavage was not observed at any time after optic
      nerve crush, suggesting that axon damage alone is insufficient to trigger
      cleavage. These findings implicate this mechanism of CaN activation in a chronic
      neurodegenerative disease. These data demonstrate that increased IOP leads to the
      initiation of a CaN-mediated mitochondrial apoptotic pathway in glaucoma and
      support neuroprotective strategies for this blinding disease.

PMID- 16103354
TI  - Quality assessment of maize assembled genomic islands (MAGIs) and large-scale
      experimental verification of predicted genes.
AB  - Recent sequencing efforts have targeted the gene-rich regions of the maize (Zea
      mays L.) genome. We report the release of an improved assembly of maize assembled
      genomic islands (MAGIs). The 114,173 resulting contigs have been subjected to
      computational and physical quality assessments. Comparisons to the sequences of
      maize bacterial artificial chromosomes suggest that at least 97% (160 of 165) of
      MAGIs are correctly assembled. Because the rates at which junction-testing PCR
      primers for genomic survey sequences (90-92%) amplify genomic DNA are not
      significantly different from those of control primers ( approximately 91%), we
      conclude that a very high percentage of genic MAGIs accurately reflect the
      structure of the maize genome. EST alignments, ab initio gene prediction, and
      sequence similarity searches of the MAGIs are available at the Iowa State
      University MAGI web site. This assembly contains 46,688 ab initio predicted
      genes. The expression of almost half (628 of 1,369) of a sample of the predicted
      genes that lack expression evidence was validated by RT-PCR. Our analyses suggest
      that the maize genome contains between approximately 33,000 and approximately
      54,000 expressed genes. Approximately 5% (32 of 628) of the maize transcripts
      discovered do not have detectable paralogs among maize ESTs or detectable
      homologs from other species in the GenBank NR nucleotide/protein database.
      Analyses therefore suggest that this assembly of the maize genome contains
      approximately 350 previously uncharacterized expressed genes. We hypothesize that
      these "orphans" evolved quickly during maize evolution and/or domestication.

PMID- 16103355
TI  - Alleles of the NRAMP1 gene are risk factors for pediatric tuberculosis disease.
AB  - Relatively little is known about the human genetics of susceptibility to common
      diseases caused by bacterial pathogens. Tuberculosis, caused by Mycobacterium
      tuberculosis, is a major cause of morbidity and mortality worldwide. So far,
      genetic studies of tuberculosis susceptibility have largely been focused on adult
      patients despite the fact that tuberculosis is highly prevalent among children.
      To study the host genetic component of pediatric tuberculosis susceptibility, we
      enrolled 184 ethnically diverse families from the Greater Houston area with at
      least one child affected by pediatric tuberculosis disease. Using a family-based
      control design, we found allelic variants of the natural resistance-associated
      macrophage protein gene 1 (NRAMP1) (alias SLC11A1) significantly associated with
      tuberculosis disease in this pediatric patient population [P = 0.01; odds ratio =
      1.75 (95% confidence interval, 1.10-2.77)]. The association of NRAMP1 with
      pediatric tuberculosis disease was significantly heterogeneous (P = 0.01) between
      simplex [P <0.0008; odds ratio = 3.13 (1.54-6.25)] and multiplex families (P =
      1), suggesting an interplay between mechanisms of genetic control and exposure
      intensities. In striking contrast to previous studies in the adult population, we
      observed that the common alleles of NRAMP1 polymorphisms were risk factors for
      pediatric tuberculosis disease. To explain the different direction of allelic
      association between adult and pediatric disease, we hypothesize that NRAMP1
      influences the speed of progression from infection to tuberculosis disease.

PMID- 16103356
TI  - Amelioration of laminin-alpha2-deficient congenital muscular dystrophy by somatic
      gene transfer of miniagrin.
AB  - Congenital muscular dystrophy (CMD) is characterized by severe muscle wasting,
      premature death in early childhood, and lack of effective treatment. Most of the
      CMD cases are caused by genetic mutations of laminin-alpha2, which is essential
      for the structural integrity of muscle extracellular matrix. Here, we report that
      somatic gene delivery of a structurally unrelated protein, a miniature version of
      agrin, functionally compensates for laminin-alpha2 deficiency in the murine
      models of CMD. Adeno-associated virus-mediated overexpression of miniagrin
      restored the structural integrity of myofiber basal lamina, inhibited
      interstitial fibrosis, and ameliorated dystrophic pathology. Furthermore,
      systemic gene delivery of miniagrin into multiple vital muscles significantly
      improved whole body growth and motility and quadrupled the lifespan (50%
      survival) of the dystrophic mice. Thus, our study demonstrated the efficacy of
      somatic gene therapy in a mouse model of CMD.

PMID- 16103357
TI  - Genetically attenuated, P36p-deficient malarial sporozoites induce protective
      immunity and apoptosis of infected liver cells.
AB  - Immunization with Plasmodium sporozoites that have been attenuated by gamma
      irradiation or specific genetic modification can induce protective immunity
      against subsequent malaria infection. The mechanism of protection is only known
      for radiation-attenuated sporozoites, involving cell-mediated and humoral immune
      responses invoked by infected hepatocytes cells that contain long-lived,
      partially developed parasites. Here we analyzed sporozoites of Plasmodium berghei
      that are deficient in P36p (p36p(-)), a member of the P48/45 family of surface
      proteins. P36p plays no role in the ability of sporozoites to infect and traverse
      hepatocytes, but p36p(-) sporozoites abort during development within the
      hepatocyte. Immunization with p36p(-) sporozoites results in a protective
      immunity against subsequent challenge with infectious wild-type sporozoites,
      another example of a specifically genetically attenuated sporozoite (GAS)
      conferring protective immunity. Comparison of biological characteristics of p36p(
      ) sporozoites with radiation-attenuated sporozoites demonstrates that liver cells
      infected with p36p(-) sporozoites disappear rapidly as a result of apoptosis of
      host cells that may potentiate the immune response. Such knowledge of the
      biological characteristics of GAS and their evoked immune responses are essential
      for further investigation of the utility of an optimized GAS-based malaria
      vaccine.

PMID- 16103358
TI  - Unifying the spatial population dynamics and molecular evolution of epidemic
      rabies virus.
AB  - Infectious disease emergence is under the simultaneous influence of both genetic
      and ecological factors. Yet, we lack a general framework for linking ecological
      dynamics of infectious disease with underlying molecular and evolutionary change.
      As a model, we illustrate the linkage between ecological and evolutionary
      dynamics in rabies virus during its epidemic expansion into eastern and southern
      Ontario. We characterized the phylogeographic relationships among 83 isolates of
      fox rabies virus variant using nucleotide sequences from the glycoprotein
      encoding glycoprotein gene. The fox rabies virus variant descended as an
      irregular wave with two arms invading from northern Ontario into southern Ontario
      over the 1980s and 1990s. Correlations between genetic and geographic distance
      suggest an isolation by distance population structure for the virus. The
      divergence among viral lineages since the most recent common ancestor correlates
      with position along the advancing wave front with more divergent lineages near
      the origin of the epidemic. Based on divergence from the most recent common
      ancestor, the regional population can be partitioned into two subpopulations,
      each corresponding to an arm of the advancing wave. Subpopulation A (southern
      Ontario) showed reduced isolation by distance relative to subpopulation B
      (eastern Ontario). The temporal dynamics of subpopulation A suggests that the
      subregional viral population may have undergone several smaller waves that
      reduced isolation by distance. The use of integrated approaches, such as the
      geographical analysis of sequence variants, coupled with information on spatial
      dynamics will become indispensable aids in understanding patterns of disease
      emergence.

PMID- 16103359
TI  - Choice reaction time performance correlates with diffusion anisotropy in white
      matter pathways supporting visuospatial attention.
AB  - Humans exhibit significant interindividual variability in behavioral reaction
      time (RT) performance yet the underlying neural mechanisms for this variability
      remain largely unknown. It has been proposed that interindividual variability in
      RT performance may be due to differences in white matter (WM) physiological
      properties, although such a relationship has never been demonstrated in cortical
      projection or association pathways in healthy young adults. Using diffusion
      tensor MRI (DTI), we sought to test whether diffusion tensor fractional
      anisotropy (FA), a measure of the orientational coherence of water self
      diffusion, is regionally correlated with RT on a visual self-paced choice RT
      (CRT) task. CRT was found to be significantly correlated with FA in projection
      and association pathways supporting visuospatial attention including the right
      optic radiation, right posterior thalamus, and right medial precuneus WM.
      Significant correlations were also observed in left superior temporal sulcus WM
      and the left parietal operculum. The lateralization of the CRT-FA correlation to
      right visual and parietal WM pathways is consistent with the specialization of
      right visual and parietal cortices for visuospatial attention. The localization
      of the CRT-FA correlations to predominantly visual and parietal WM pathways, but
      not to motor pathways or the corpus callosum indicates that individual
      differences in visual CRT performance are associated with variations in the WM
      underlying the visuospatial attention network as opposed to pathways supporting
      motor movement or interhemispheric transmission.

PMID- 16103360
TI  - Bohr's 1913 molecular model revisited.
AB  - It is generally believed that the old quantum theory, as presented by Niels Bohr
      in 1913, fails when applied to few electron systems, such as the H(2) molecule.
      Here, we find previously undescribed solutions within the Bohr theory that
      describe the potential energy curve for the lowest singlet and triplet states of
      H(2) about as well as the early wave mechanical treatment of Heitler and London.
      We also develop an interpolation scheme that substantially improves the agreement
      with the exact ground-state potential curve of H(2) and provides a good
      description of more complicated molecules such as LiH, Li(2), BeH, and He(2).

PMID- 16103361
TI  - Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal.
AB  - Acetyl-CoA carboxylases (ACC1 and ACC2) catalyze the carboxylation of acetyl-CoA
      to form malonyl-CoA, an intermediate metabolite that plays a pivotal role in the
      regulation of fatty acid metabolism. We previously reported that ACC2 null mice
      are viable, and that ACC2 plays an important role in the regulation of fatty acid
      oxidation through the inhibition of carnitine palmitoyltransferase I, a
      mitochondrial component of the fatty-acyl shuttle system. Herein, we used gene
      targeting to knock out the ACC1 gene. The heterozygous mutant mice (Acc1(+/-))
      had normal fertility and lifespans and maintained a similar body weight to that
      of their wild-type cohorts. The mRNA level of ACC1 in the tissues of Acc1(+/-)
      mice was half that of the wild type; however, the protein level of ACC1 and the
      total malonyl-CoA level were similar. In addition, there was no difference in the
      acetate incorporation into fatty acids nor in the fatty acid oxidation between
      the hepatocytes of Acc1(+/-) mice and those of the wild type. In contrast to
      Acc2(-/-) mice, Acc1(-/-) mice were not detected after mating. Timed pregnancies
      of heterozygotes revealed that Acc(-/-) embryos are already undeveloped at
      embryonic day (E)7.5, they die by E8.5, and are completely resorbed at E11.5. Our
      previous results of the ACC2 knockout mice and current studies of ACC1 knockout
      mice further confirm our hypotheses that malonyl-CoA exists in two independent
      pools, and that ACC1 and ACC2 have distinct roles in fatty acid metabolism.

PMID- 16103362
TI  - X-ray damage to the Mn4Ca complex in single crystals of photosystem II: a case
      study for metalloprotein crystallography.
AB  - X-ray absorption spectroscopy was used to measure the damage caused by exposure
      to x-rays to the Mn(4)Ca active site in single crystals of photosystem II as a
      function of dose and energy of x-rays, temperature, and time. These studies
      reveal that the conditions used for structure determination by x-ray
      crystallography cause serious damage specifically to the metal-site structure.
      The x-ray absorption spectra show that the structure changes from one that is
      characteristic of a high-valent Mn(4)(III(2),IV(2)) oxo-bridged Mn(4)Ca cluster
      to that of Mn(II) in aqueous solution. This damage to the metal site occurs at a
      dose that is more than one order of magnitude lower than the dose that results in
      loss of diffractivity and is commonly considered safe for protein
      crystallography. These results establish quantitative x-ray dose parameters that
      are applicable to redox-active metalloproteins. This case study shows that a
      careful evaluation of the structural intactness of the active site(s) by
      spectroscopic techniques can validate structures derived from crystallography and
      that it can be a valuable complementary method before structure-function
      correlations of metalloproteins can be made on the basis of high-resolution x-ray
      crystal structures.

PMID- 16103363
TI  - An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin
      bioactivation.
AB  - The identity of the cellular mechanisms through which nitroglycerin (glyceryl
      trinitrate, GTN) elicits nitric oxide (NO)-based signaling to dilate blood
      vessels remains one of the longest standing foci of investigation and sources of
      controversy in cardiovascular biology. Recent evidence suggests an unexpected
      role for mitochondria. We show here that bioconversion by mitochondria of
      clinically relevant concentrations of GTN results in activation of guanylate
      cyclase, production of cGMP, vasodilation in vitro, and lowered blood pressure in
      vivo, which are eliminated by genetic deletion of the mitochondrial aldehyde
      dehydrogenase (mtALDH). In contrast, generation of vasoactivity from alternative
      nitro(so)-vasodilators is unaffected. In mtALDH(-/-) mice and their isolated
      vascular tissue, GTN bioactivity can still be generated, but only at
      substantially higher concentrations of GTN and by a mechanism that does not
      exhibit tolerance. Thus, mtALDH is necessary and sufficient for vasoactivity
      derived from therapeutic levels of GTN, and, more generally, mitochondria can
      serve as a source of NO-based cellular signals that may originate independently
      of NO synthase activity.

PMID- 16103364
TI  - Unraveling a role for dopamine in Huntington's disease: the dual role of reactive
      oxygen species and D2 receptor stimulation.
AB  - Huntington's disease (HD), an inherited neurodegenerative disorder, results from
      an abnormal polyglutamine extension in the N-terminal region of the huntingtin
      protein. This mutation leads to protein aggregation and neurotoxicity. Despite
      its widespread expression in the brain and body, mutated huntingtin causes
      selective degeneration of striatal projection neurons. In the present study, we
      investigate the role of dopamine (DA) in this preferential vulnerability. Using
      primary cultures of striatal neurons transiently expressing GFP-tagged-exon 1 of
      mutated huntingtin, we show that low doses of DA (100 microM) act synergistically
      with mutated huntingtin to activate the proapoptotic transcription factor c-Jun.
      Surprisingly, DA also increases aggregate formation of mutated huntingtin in all
      cellular compartments, including neurites, soma, and nuclei. DA-dependent
      potentiation of c-Jun activation was reversed by ascorbate, a reactive oxygen
      species (ROS) scavenger, and SP-600125, a selective inhibitor of the c-Jun N
      terminal kinase (JNK) pathway. By contrast, DA effects on aggregate formation
      were reversed by a selective D2 receptor antagonist and reproduced by a D2
      agonist. Similarly, striatal neurons from D2 knockout mice showed no effect of DA
      on aggregate formation. Blocking ROS production, JNK activation, or D2 receptor
      stimulation significantly reversed DA aggravation of mutated huntingtin-induced
      striatal death. The combined treatment with the ROS scavenger and D2 antagonist
      totally reversed DA's effects on mutated huntingtin-induced striatal death. Thus,
      the present results provide insights into the cellular mechanisms that govern
      striatal vulnerability in HD and strongly support a dual role of JNK activation
      and D2 receptor signaling in this process.

PMID- 16103365
TI  - Monte Carlo modeling of single-molecule cytoplasmic dynein.
AB  - Molecular motors are responsible for active transport and organization in the
      cell, underlying an enormous number of crucial biological processes. Dynein is
      more complicated in its structure and function than other motors. Recent
      experiments have found that, unlike other motors, dynein can take different size
      steps along microtubules depending on load and ATP concentration. We use Monte
      Carlo simulations to model the molecular motor function of cytoplasmic dynein at
      the single-molecule level. The theory relates dynein's enzymatic properties to
      its mechanical force production. Our simulations reproduce the main features of
      recent single-molecule experiments that found a discrete distribution of dynein
      step sizes, depending on load and ATP concentration. The model reproduces the
      large steps found experimentally under high ATP and no load by assuming that the
      ATP binding affinities at the secondary sites decrease as the number of ATP bound
      to these sites increases. Additionally, to capture the essential features of the
      step-size distribution at very low ATP concentration and no load, the ATP
      hydrolysis of the primary site must be dramatically reduced when none of the
      secondary sites have ATP bound to them. We make testable predictions that should
      guide future experiments related to dynein function.

PMID- 16103366
TI  - Ca2+ sparks and secretion in dorsal root ganglion neurons.
AB  - Ca(2+) sparks as the elementary intracellular Ca(2+) release events are
      instrumental to local control of Ca(2+) signaling in many types of cells. Here,
      we visualized neural Ca(2+) sparks in dorsal root ganglion (DRG) sensory neurons
      and investigated possible role of DRG sparks in the regulation of secretion from
      the somata of the cell. DRG sparks arose mainly from type 3 ryanodine receptor
      Ca(2+) release channels on subsurface cisternae of the endoplasmic reticulum,
      rendering a striking subsurface localization. Caffeine- or 3,7-dimethyl-1-(2
      propynyl)xanthine-induced store Ca(2+) release, in the form of Ca(2+) sparks,
      triggered exocytosis, independently of membrane depolarization and external
      Ca(2+). The spark-secretion coupling probability was estimated to be between 1
      vesicle per 6.6 sparks and 1 vesicle per 11.4 sparks. During excitation,
      subsurface sparks were evoked by physiological Ca(2+) entry via the Ca(2+)
      induced Ca(2+) release mechanism, and their synergistic interaction with Ca(2+)
      influx accounted for approximately 60% of the Ca(2+)-dependent exocytosis.
      Furthermore, inhibition of Ca(2+)-induced Ca(2+) release abolished endotoxin
      induced secretion of pain-related neuropeptides. These findings underscore an
      important role for Ca(2+) sparks in the amplification of surface Ca(2+) influx
      and regulation of neural secretion.

PMID- 16103367
TI  - A role for transferrin receptor in triggering apoptosis when targeted with
      gambogic acid.
AB  - Transferrin receptor (TfR) has been shown to be significantly overexpressed in
      different types of cancers. We discovered TfR as a target for gambogic acid (GA),
      used in traditional Chinese medicine and a previously undiscovered link between
      TfR and the rapid activation of apoptosis. The binding site of GA on TfR is
      independent of the transferrin binding site, and it appears that GA potentially
      inhibits TfR internalization. Down-regulation of TfR by RNA interference
      decreases sensitivity to GA-induced apoptosis, further supporting TfR as the
      primary GA receptor. In summary, GA binding to TfR induces a unique signal
      leading to rapid apoptosis of tumor cells. These results suggest that GA may
      provide an additional approach for targeting the TfR and its use in cancer
      therapy.

PMID- 16103368
TI  - Identification of an interactor of cadmium ion-induced glycine-rich protein
      involved in regulation of callose levels in plant vasculature.
AB  - Cadmium-induced glycine-rich protein (cdiGRP) is a cell wall-associated factor
      that increases callose levels in plant vasculature. To better understand the
      cdiGRP/callose regulation system, we identified a tobacco protein, GrIP (cdiGRP
      interacting protein, GrIP), that associates with cdiGRP and localizes at the
      plant cell wall. Constitutive overexpression of GrIP enhanced the accumulation of
      the cdiGRP protein and callose in vasculature-associated cells with or without
      treatment with cadmium ions. That GrIP gene expression was not affected by
      cadmium ions indicated that GrIP does not directly modulate the callose levels
      induced by the treatment. Instead, GrIP most likely functions by further
      elevating the accumulated amount of cdiGRP, the expression of which is up
      regulated by the cadmium ions. Interestingly, the levels of cdiGRP mRNA were not
      affected by constitutive expression of GrIP, demonstrating that the enhancement
      in cdiGRP protein accumulation by GrIP overexpression occurs posttranslationally.
      Collectively, these observations suggest that GrIP interacts with cdiGRP and
      increases its level of accumulation; in turn, the elevated amounts of cdiGRP
      induce callose deposits in the plant cell walls. Therefore, GrIP and cdiGRP
      represent sequentially acting factors in a biochemical pathway that regulates
      callose accumulation in the plant vasculature.

PMID- 16103369
TI  - Microoxen: microorganisms to move microscale loads.
AB  - It is difficult to harness the power generated by biological motors to carry out
      mechanical work in systems outside the cell. Efforts to capture the mechanical
      energy of nanomotors ex vivo require in vitro reconstitution of motor proteins
      and, often, protein engineering. This study presents a method for harnessing the
      power produced by biological motors that uses intact cells. The unicellular,
      biflagellated algae Chlamydomonas reinhardtii serve as "microoxen." This method
      uses surface chemistry to attach loads (1- to 6-microm-diameter polystyrene
      beads) to cells, phototaxis to steer swimming cells, and photochemistry to
      release loads. These motile microorganisms can transport microscale loads (3
      microm-diameter beads) at velocities of approximately 100-200 microm.sec(-1) and
      over distances as large as 20 cm.

PMID- 16103370
TI  - Sequence optimization and designability of enzyme active sites.
AB  - We recently found that many residues in enzyme active sites can be
      computationally predicted by the optimization of scoring functions based on
      substrate binding affinity, subject to constraints on the geometry of catalytic
      residues and protein stability. Here, we explore the generality of this
      surprising observation. First, the impact of hydrogen-bonding networks necessary
      for catalysis on the accuracy of sequence optimization is assessed; incorporation
      of these networks, where relevant, into the set of catalytic constraints is found
      to be essential. Next, the impact of multiple substrate selectivity on sequence
      optimization is probed by carrying out independent calculations for complexes of
      deoxyribonucleoside kinases with various cognate ligands, revealing how
      simultaneous selection pressures determined active-site sequences of these
      enzymes. Including previous calculations on simpler enzymes, computational
      sequence optimization correctly predicts 76% of all active-site residues tested
      (86% correct, with 93% similar, for naturally conserved residues). In these
      studies, the ligand is fixed in its native conformation. To assess the
      applicability of these methods to de novo active-site design, the effect of small
      ligand motions around the native pose is also examined. Robustness of sequence
      accuracy for topologically similar poses is demonstrated for selected kinases,
      but not for a model peptidase. Based on these observations, we introduce the
      notion of the designability of an enzyme active site, a metric that may be used
      to guide the search for protein scaffolds suitable for the introduction of de
      novo activity for a desired chemical reaction.

PMID- 16103371
TI  - Pungent products from garlic activate the sensory ion channel TRPA1.
AB  - Garlic belongs to the Allium family of plants that produce organosulfur
      compounds, such as allicin and diallyl disulfide (DADS), which account for their
      pungency and spicy aroma. Many health benefits have been ascribed to Allium
      extracts, including hypotensive and vasorelaxant activities. However, the
      molecular mechanisms underlying these effects remain unknown. Intriguingly,
      allicin and DADS share structural similarities with allyl isothiocyanate, the
      pungent ingredient in wasabi and other mustard plants that induces pain and
      inflammation by activating TRPA1, an excitatory ion channel on primary sensory
      neurons of the pain pathway. Here we show that allicin and DADS excite an allyl
      isothiocyanate-sensitive subpopulation of sensory neurons and induce vasodilation
      by activating capsaicin-sensitive perivascular sensory nerve endings. Moreover,
      allicin and DADS activate the cloned TRPA1 channel when expressed in heterologous
      systems. These and other results suggest that garlic excites sensory neurons
      primarily through activation of TRPA1. Thus different plant genera, including
      Allium and Brassica, have developed evolutionary convergent strategies that
      target TRPA1 channels on sensory nerve endings to achieve chemical deterrence.

PMID- 16103372
TI  - Methanococcus vannielii selenium-binding protein (SeBP): chemical reactivity of
      recombinant SeBP produced in Escherichia coli.
AB  - A selenium-binding protein (SeBP) from Methanococcus vannielii was recently
      identified, and its gene was isolated and overexpressed in Escherichia coli
      [Self, W. T., Pierce, R. & Stadtman, T. C. (2004) IUBMB Life 56, 501-507]. SeBP
      and recombinant SeBP (rSeBP) migrated as approximately 42-kDa species on native
      gels and as approximately 33-kDa species on SDS gels. rSeBP consists of identical
      8.8-kDa subunits, each containing a single cysteine residue. rSeBP isolated in
      the absence of reducing agents contained oxidized cysteine (89%) and very little
      bound selenium (0.05 eq or less per subunit). Complete reduction of the oxidized
      cysteine residues in rSeBP with Tris(2-carboxyethyl)phosphine required addition
      of a denaturant, such as 1 M guanidine-hydrochloride. With selenite as the
      selenium source and the isolated reduced protein as sole reductant, binding of
      one selenium per tetramer under anaerobic conditions required four cysteine thiol
      groups, one on each subunit. In the corresponding reaction, with reduced
      glutathione (GSH), equimolar amounts of selenodiglutathione (GSSeSG) and
      glutathione disulfide are formed from selenite and 4 GSH. At GSH-to-selenite
      ratios >4:1, conversion of GSSeSG to a perselenide derivative, GSSe(-), occurs.
      However, with the reduced rSeBP as sole electron donor in the reaction with
      selenite, further conversion of the R-SSeS-R product apparently did not occur.
      Prior alkylation of the cysteine thiol groups in reduced rSeBP prevented selenite
      reduction and selenium binding under comparable conditions.

PMID- 16103373
TI  - Coupled biophysical global ocean model and molecular genetic analyses identify
      multiple introductions of cryptogenic species.
AB  - The anthropogenic introduction of exotic species is one of the greatest modern
      threats to marine biodiversity. Yet exotic species introductions remain difficult
      to predict and are easily misunderstood because knowledge of natural dispersal
      patterns, species diversity, and biogeography is often insufficient to
      distinguish between a broadly dispersed natural population and an exotic one.
      Here we compare a global molecular phylogeny of a representative marine
      meroplanktonic taxon, the moon-jellyfish Aurelia, with natural dispersion
      patterns predicted by a global biophysical ocean model. Despite assumed high
      dispersal ability, the phylogeny reveals many cryptic species and predominantly
      regional structure with one notable exception: the globally distributed Aurelia
      sp.1, which, molecular data suggest, may occasionally traverse the Pacific
      unaided. This possibility is refuted by the ocean model, which shows much more
      limited dispersion and patterns of distribution broadly consistent with modern
      biogeographic zones, thus identifying multiple introductions worldwide of this
      cryptogenic species. This approach also supports existing evidence that (i) the
      occurrence in Hawaii of Aurelia sp. 4 and other native Indo-West Pacific species
      with similar life histories is most likely due to anthropogenic translocation,
      and (ii) there may be a route for rare natural colonization of northeast North
      America by the European marine snail Littorina littorea, whose status as endemic
      or exotic is unclear.

PMID- 16103374
TI  - Endocytosis and degradation of BOR1, a boron transporter of Arabidopsis thaliana,
      regulated by boron availability.
AB  - Boron (B) is essential for plants but toxic when present in excess. Arabidopsis
      thaliana BOR1 is a B exporter for xylem loading and is essential for efficient B
      translocation from roots to shoots under B limitation. B translocation to shoots
      was enhanced under B limitation in WT but not in bor1-1 mutant plants. The
      enhanced translocation was suppressed upon resupply of high levels of B within
      several hours. Unlike a number of transporters for essential mineral nutrients,
      BOR1 mRNA accumulation was not strongly affected by B conditions. However,
      accumulation of a constitutively expressed BOR1-GFP fusion protein was elevated
      under conditions of limited B supply. Upon resupply of high levels of B, BOR1-GFP
      was degraded within several hours. These findings demonstrate that
      posttranscriptional mechanisms play a major role in regulation of BOR1
      accumulation. Confocal laser scanning microscopy of root tip cells showed that
      BOR1-GFP is localized to the plasma membrane under B limitation. Shortly after B
      application, the protein was observed in dot-like structures in the cytoplasm
      before degradation. Colocalization studies of the fusion protein with an
      endocytic tracer FM4-64 and an endosomal Rab-GTPase Ara7 fused to monomeric red
      fluorescent protein suggested that BOR1 is transferred from the plasma membrane
      via the endosomes to the vacuole for degradation. These results establish that
      endocytosis and degradation of BOR1 are regulated by B availability, to avoid
      accumulation of toxic levels of B in shoots under high-B supply, while protecting
      the shoot from B deficiency under B limitation.

PMID- 16103375
TI  - Rho GTPases dictate the mobility of the Na/H exchanger NHE3 in epithelia: role in
      apical retention and targeting.
AB  - Proximal tubular reabsorption of filtered sodium by the sodium/hydrogen exchanger
      isoform 3 (NHE3), located on the apical membrane, is fundamental to the
      maintenance of systemic volume and pH homeostasis. NHE3 is finely regulated by a
      variety of hormones and by changes in ionic composition and volume, likely
      requiring redistribution of the exchangers. We analyzed the subcellular
      distribution and dynamics of the exchangers by generating an epithelial line
      expressing NHE3 tagged with an exofacial epitope, which enabled us to monitor
      exchanger mobility and traffic in intact cells. Using determinations of
      fluorescence recovery after photobleaching in combination with dynamic
      measurements of subcellular distribution, we found that, in renal epithelial
      cells, NHE3 exists in four distinct subcompartments: a virtually immobile
      subpopulation that is retained on the apical membrane by interaction with the
      actin cytoskeleton in a manner that depends on the sustained activity of Rho
      GTPases; a mobile subpopulation on the apical membrane, which can be readily
      internalized; and two intracellular compartments that can be differentiated by
      their rate of exchange with the apical pool of NHE3. We provide evidence that
      detachment of the immobile fraction from its cytoskeletal anchorage leads to
      rapid internalization. These observations suggest that modulation of the mobile
      fraction of NHE3 on the apical membrane can alter the number of functional
      exchangers on the cell surface and, consequently, the rate of transepithelial ion
      transport. Regulation of the interaction of NHE3 with the actin cytoskeleton can
      therefore provide a new mode of regulation of sodium and hydrogen transport.

PMID- 16103376
TI  - Perioperative methemoglobinemia.

PMID- 16103377
TI  - Should cuffed endotracheal tubes be used routinely in children?

PMID- 16103378
TI  - Current preoperative testing practices in ambulatory surgery are widely
      disparate: a survey of CAS members.
AB  - PURPOSE: Routine preoperative testing has been criticized as having little impact
      on perioperative outcomes. The purpose of this study is to identify the current
      practice of preoperative testing in ambulatory surgery. METHODS: A standard
      questionnaire was sent to all active members of the Canadian Anesthesiologists'
      Society (CAS). The study inquired into the anesthesiologist's preoperative
      testing practice in healthy patients and patients with stable medical conditions
      undergoing ambulatory surgery. RESULTS: Of 1,335 mailed questionnaires, a total
      617 respondents who reported their participation in ambulatory surgical care were
      received. Eighty percent [95% confidence interval (CI) 76.5-83.2] of the
      respondents indicated that, if testing had to be ordered in asymptomatic patients
      undergoing low-risk ambulatory surgery, it would be due to the patient's clinical
      indications while others indicated it would be the result of following
      institutional guidelines (15.1%, 95% CI 12.2-17.9), and even fewer attributed it
      to a "routine" testing practice (0.5%, 95% CI 0-1.14). Forty-four percent (95% CI
      39.8-47.8) of the anesthesiologists indicated that age alone is not a criterion
      when they required a preoperative electrocardiogram (ECG) while others reported
      various cut-points (> 65; > 55; > 45; > 40 yr) for ECG ordering for asymptomatic
      patients undergoing the low-risk ambulatory surgery. About 40% (95% CI 35.7-43.5)
      of the anesthesiologists had no specific concern about eliminating preoperative
      testing in ambulatory surgery. CONCLUSION: Our survey has documented marked
      disparities in the practices of preoperative testing. A large proportion of the
      anesthesiologists indicated that age alone is not a criterion for preoperative
      ordering of ECG. Many anesthesiologists had no concern about eliminating
      preoperative testing in low-risk ambulatory surgery.

PMID- 16103379
TI  - A survey of British Columbia anesthesiologists on a provincial critical incident
      reporting program.
AB  - PURPOSE: To determine why British Columbia's anesthesiologists have not actively
      participated in a provincial Critical Incident Reporting Service by submitting
      reports of critical incidents experienced in their practice. METHODS: An email
      and postal mail survey of BC anesthesiologists was undertaken, proposing a
      variety of reasons why critical incidents may not be reported to the Service.
      RESULTS: 207 responses were received from 368 specialist and general practitioner
      anesthesiologists. Respondents indicated general satisfaction with the overall
      concept of having an incident reporting service, and with the design of the multi
      page reporting form. The greatest perceived problems to reporting incidents were
      related to aspects of workload, fear of litigation or a record of problems, and
      difficulties with the terminology of incident and error reporting. There are
      implications to the establishment of broader based programs in Canada.
      CONCLUSION: A number of factors are responsible for under reporting of critical
      events. Further efforts to encourage reporting are required.

PMID- 16103380
TI  - Syringe pump displacement alters line internal pressure and flow.
AB  - PURPOSE: It has been reported that the actual flow from a syringe pump changes
      due to vertical movement of the pump in vitro, but a direct study of the in vivo
      effects of fluid delivery irregularities caused by vertical pump displacement has
      not been performed. The aim of this study was to assess the influence of
      positional changes of the syringe pump on the internal pressure (IP) and flow
      from the circuit, and to examine blood pressure changes caused by pump movement
      in animals with or without hemorrhagic shock. METHODS: To simulate clinical
      conditions, we used a rabbit model. We first measured the changes in line IP and
      flow from the syringe pump after moving the pump 50 cm vertically upwards or
      downwards. With the same animal, we then recorded the blood pressure changes
      under these conditions during norepinephrine (NE) infusion, using a rabbit
      hemorrhagic shock (HS) model. RESULTS: Following downward movement of the syringe
      pump, the IP increased by 37.5 +/- 4.0 mmHg and IP decreased by 37.3 +/- 3.1 mmHg
      following upward movement of the syringe pump. In the rabbit HS model, movement
      downwards decreased systolic blood pressure (SBP) by -17 +/- 6.9% (P < 0.001),
      while upward movement raised SBP by 45.7 +/- 21.5% (P < 0.001) from baseline
      values. CONCLUSIONS: Vertical displacement of the syringe pump alters the flow
      due to a change of line IP, and blood pressure can be affected by pump movement
      during NE infusion.

PMID- 16103381
TI  - Preoperative medical consultations: impact on perioperative management and
      surgical outcome.
AB  - PURPOSE: This study was designed to assess the effect of preoperative medical
      consults on both perioperative management and surgical outcome. METHODS: The
      charts of 387 consecutive patients over the age of 50 undergoing non-cardiac,
      elective surgery during a six-week period were retrospectively examined. Patient
      factors including age, ASA status, gender, type of surgery, outcome (death,
      unexpected intensive care unit admission or uncomplicated discharge), presence of
      medical consult, and, in those cases where a medical consult was present, stated
      reason for the consult, the ordering physician, and recommendations of the
      consultant, were recorded. RESULTS: 138 patients receiving medical consults
      (35.7%) were identified (a total of 146 consults). The most common stated purpose
      of the consults examined was "preoperative evaluation." In only five consults
      (3.4%) did the consultant identify a new finding. Sixty-two consults (42.5%)
      contained no recommendations. There was no statistically significant difference
      in outcome between those patients who received a medical consult and those who
      did not. CONCLUSION: A review of 146 medical consults suggests that the majority
      of such consults give little advice that truly impacts either perioperative
      management or outcome of surgery.

PMID- 16103382
TI  - P6 acupressure increases tolerance to nauseogenic motion stimulation in women at
      high risk for PONV.
AB  - PURPOSE: In a previous study we noticed that P6 acupressure decreased
      postoperative nausea and vomiting (PONV) more markedly after discharge. As motion
      sickness susceptibility is increased by, for example, opioids we hypothesized
      that P6 acu-pressure decreased PONV by decreasing motion sickness susceptibility.
      We studied time to nausea by a laboratory motion challenge in a group of
      volunteers, during P6 and placebo acupressure. METHODS: 60 women with high and
      low susceptibilities for motion sickness participated in a randomized and double
      blind study with an active P6 acupressure, placebo acupressure, and a control
      group (n = 20 in each group). The risk score for PONV was over 50%. The motion
      challenge was by eccentric rotation in a chair, blindfolded and with chin to
      chest movements of the head. The challenge was stopped when women reported
      moderate nausea. Symptoms were recorded. RESULTS: Mean time to moderate nausea
      was longer in the P6 acu-pressure group compared to the control group. P6
      acupressure = 352 (259-445), mean (95% confidence interval) in seconds, control =
      151 (121-181) and placebo acupressure = 280 (161-340); (P = 0.006). No difference
      was found between P6 and placebo acupressure or placebo acupressure and control
      groups. Previous severity of motion sickness did not influence time to nausea (P
      = 0.107). The cumulative number of symptoms differed between the three groups (P
      < 0.05). Fewer symptoms were reported in the P6 acupressure compared to the
      control group P < 0.009. Overall, P6 acupressure was only marginally more
      effective than placebo acupressure on the forearms. CONCLUSION: In females with a
      history of motion sickness P6 acu-pressure increased tolerance to experimental
      nauseogenic stimuli, and reduced the total number of symptoms reported.

PMID- 16103383
TI  - [Thoracic epidural and intrathecal analgesia have similar effects on pain relief
      and respiratory function after thoracic surgery].
AB  - PURPOSE: To compare in a prospective randomized trial the effects of thoracic
      epidural infusions of fentanyl (F) and bupivacaine (B) to intrathecal morphine
      (M) and sufentanil (S) on analgesia and respiratory function following
      thoracotomy. PATIENTS AND METHODS: 55 patients undergoing an elective postero
      lateral thoracotomy were randomly assigned to one of two groups: Group I (n =
      27): received intrathecal S (5 microg) and M (0.5 mg) one hour before surgery.
      Group II (n = 28) received, after induction of anesthesia, an initial dose of 10
      to 20 mL of a solution of B 0.25% and F 2 microg.mL(-1) via an epidural thoracic
      catheter previously inserted between T5 and T8. The same solution was infused
      during surgery. After surgery, patients received a continuous infusion of B 0.1%
      and F 2 microg.mL(-1) with a bolus every 15 min if needed. Heart rate (HR), mean
      arterial pressure (MAP), SpO(2), PaCO(2), respiratory rate (RR), forced
      expiratory volume in one second, peak expiratory flow rate and forced vital
      capacity were recorded at different times from the day before surgery till T48 =
      48 hr after surgery. Subjective pain was assessed using a 10 cm visual analogue
      scale (VAS) scoring at rest and during cough. RESULTS: No significant difference
      was noted between both groups concerning VAS, HR, MAP, SpO(2), PaCO(2) and RR.
      Variations of the respiratory function tests were identical in both groups.
      CONCLUSION: This study shows that intrathecal M and S offer analgesia comparable
      to thoracic epidural infusion of B and F.

PMID- 16103384
TI  - Case series: Ultrasonography may assist epidural insertion in scoliosis patients.
AB  - PURPOSE: Epidural cannulation is a difficult technique in the patient undergoing
      scoliosis repair, due to axial rotation of the vertebral bodies, as well as
      angulation of the spinal processes. This case series was performed to investigate
      whether ultrasonography could facilitate epidural insertion in patients with
      scoliosis, by assessing the degree of vertebral body rotation. CLINICAL FEATURES:
      Eleven patients scheduled for corrective scoliosis surgery were studied. The
      spine was examined ultrasonically using a portable ultrasound system with a 38-mm
      linear probe in two-dimensional B mode. The angulation of the probe head
      (measured using an inclinometer held in alignment with its long axis) at which
      the echo signals from the laminae became level on the screen was taken to
      correspond to the degree of vertebral rotation. The least rotated (most neutral)
      vertebral interspace was located, and a supervised anesthesiology trainee then
      performed epidural catheter insertion, using a loss-of-resistance technique.
      Bupivacaine 0.125% with fentanyl 4 mug.mL(-1) was infused after surgery, and
      successful epidural placement was indicated by the presence of effective
      analgesia and loss of sensation to cold stimuli. In ten patients, the neutral
      space could be identified, while in one, the least rotated space was measured at
      15 degrees from the horizontal. Epidural catheterization was successful in eight
      of 11 patients at the identified level. In two other patients, the space above
      was employed. The information was described as helpful in seven patients.
      CONCLUSION: We conclude that ultrasonography may have a potential role to
      facilitate insertion of epidural catheters in patients with scoliosis.

PMID- 16103385
TI  - Intubation depth markings allow an improved positioning of endotracheal tubes in
      children.
AB  - OBJECTIVES: To evaluate the position of the new Microcuff pediatric tracheal
      tube, based upon intubation depth markings. METHODS: With Institutional Ethics
      Committee approval and informed parental consent, we included patients from birth
      (> or = 3 kg) to 16 yr undergoing interventional cardiac catheterization
      requiring general anesthesia with orotracheal intubation. The intubation depth
      mark of the tracheal tube was placed between the vocal cords by direct
      laryngoscopy. The distance between tube tip and tracheal carina was measured from
      routinely taken cardiac catheterization posterior-anterior x-ray computer images
      with the patient supine and the head in a neutral position. Evaluation was
      performed for 20 tubes size 3.0 mm internal diameter (ID) and for ten tubes of
      each size from 3.5 to 7.0 mm ID. RESULTS: 100 patients were studied (47 girls; 53
      boys). Tracheal tube tip advancement into the trachea ranged from 40.6% to 68.6%
      (median 51.4%). The shortest distance from tube tip to the tracheal carina was
      15.7 mm using a 3.0 mm ID tube. Using a standard formula for tube insertion in
      children aged > or = two years [12 cm + (age/2)], in one patient the tube tip
      would have been below the carina and in seven patients the tube cuffs would have
      been placed within the larynx. CONCLUSIONS: The intubation depth markings of the
      new Microcuff pediatric tracheal tube allow safe placement of the tracheal tube
      with a cuff-free laryngeal zone without the risk for endobronchial intubation.
      Placement using the intubation depth markings was superior to predicted insertion
      using a standard formula.

PMID- 16103386
TI  - Recurrent seizure activity after epidural morphine in a post-partum woman.
AB  - PURPOSE: We report on a primiparous woman who suffered recurrent seizure activity
      after repeated small doses of epidural morphine to highlight the neuroexcitation
      potential of neuraxial opioids in the epileptic patient. CLINICAL FEATURES:
      Seizure activities as a complication of opioid administration have been reported
      in laboratory animals and humans. We report the case of a 30-yr-old primiparous
      woman with a history of epilepsy under carbamazepine treatment, who had epidural
      anesthesia for elective Cesarean section at 38 weeks gestation. Postoperatively,
      1.5 mg of morphine were administered epidurally for pain control. Three hours
      later the patient suffered from clonic movements of the right arm without loss of
      consciousness. One day later, she again received 1 mg of epidural morphine twice
      at a 12-hr interval and similar seizure episodes recurred eight hours after each
      dose. A relation between the administration of morphine and seizure activity was
      suspected and the use of opioids for pain control was stopped. The patient was
      discharged on the fifth postoperative day and, more than one year after the last
      episode, she remains free of any seizure activity. CONCLUSION: Our report
      indicates that even a remote history of epilepsy carries a pro-convulsant
      potential in the peripartum period, even following the administration of small
      doses of epidural morphine.

PMID- 16103387
TI  - Dexmedetomidine sedation in a pediatric cardiac patient scheduled for MRI.
AB  - PURPOSE: To describe the use of dexmedetomidine for sedation in a critically ill
      infant undergoing magnetic resonance imaging (MRI). CLINICAL FEATURES: A nine
      month-old 5.1 kg infant was to have an MRI study of the thorax. The infant had
      multiple congenital cardiac anomalies which had been partially corrected
      surgically. After administration of atropine, 0.1 mg iv, a loading dose of
      dexmedetomidine (1 microg.kg(-1) iv) was administered over ten minutes followed
      by a continuous infusion of 0.5 microg.kg(-1).hr(-1) for maintenance. Propofol 5
      mg iv were administered after the loading dose of dexemedetomidine to produce
      somnolence. Anesthetic conditions for performing the MRI were excellent. The
      infant remained motionless, breathing spontaneously. Hemodynamics remained stable
      throughout the procedure. Recovery was rapid and uneventful. CONCLUSION:
      Dexmedetomidine and a small dose of propofol were used successfully to sedate a
      critically ill infant for MRI. More studies are required to determine the role of
      this unique drug in the pediatric population.

PMID- 16103388
TI  - Perioperative anesthetic management for Cesarean section of a parturient with
      gestational diabetes insipidus.
AB  - PURPOSE: Gestational diabetes insipidus (GDI) is a rare endocrinopathy
      complicating about 4:100,000 deliveries. We present the case of a preterm
      parturient with GDI and severe hypernatremia (serum sodium concentration = 174
      mmol.L(-1)) presenting for an urgent Cesarean section. CLINICAL FEATURES: Fluid
      resuscitation and desmopressin supplementation partially corrected the patient's
      homeostasis, allowing us to carefully titrate epidural anesthesia for an urgent
      Cesarean section. After delivery, the patient was transferred to the intensive
      care unit. The serum sodium concentration of the mother and the neonate was
      normalized over 48 hr and three days respectively. CONCLUSION: The careful
      perioperative management of GDI led to a favourable outcome of the mother and
      fetus.

PMID- 16103389
TI  - Images in anesthesia: Transesophageal echocardiography during Cesarean section in
      a Marfan's patient with aortic dissection.

PMID- 16103390
TI  - The ProSeal laryngeal mask airway: a review of the literature.
AB  - PURPOSE: To analyze and summarize the published literature relating to the
      ProSeal LMA (PLMA): a modification of the "classic LMA" (cLMA) with an esophageal
      drain tube (DT), designed to improve controlled ventilation, airway protection
      and diagnosis of misplacement. SOURCE: Articles identified through Medline and
      EMBASE searches using keywords "Proseal", "ProSeal" and "PLMA". Hand searches of
      these articles and major anesthetic journals from January 1998 to March 2005.
      PRINCIPAL FINDINGS: Searches identified 59 randomized controlled trials or
      clinical studies and 79 other publications. Compared to the cLMA, PLMA insertion
      takes a few seconds longer. First attempt insertion success for the PLMA is
      lower, but overall success is equivalent. Airway seal is improved by 50%. The DT
      enables early diagnosis of mask misplacement, allows gastric drainage, reduces
      gastric inflation and may vent regurgitated stomach contents. Evidence suggests,
      but does not prove, that the correctly placed PLMA reduces aspiration risk
      compared with the cLMA. PLMA use is associated with less coughing and less
      hemodynamic disturbance than use of a tracheal tube (TT). Comparative trials of
      the PLMA with other supraglottic airways favour the PLMA. Clinicians have
      extended the use of the PLMA inside and outside the operating theatre including
      use for difficult airway management and airway rescue. CONCLUSIONS: The PLMA has
      similar insertion characteristics and complications to other laryngeal masks. The
      DT enables rapid diagnosis of misplacement. The PLMA offers significant benefits
      over both the cLMA and TT in some clinical circumstances. These and clinical
      experience with the PLMA are discussed.

PMID- 16103391
TI  - Obstructive sleep apnea uncovered after high spinal anesthesia: a case report.
AB  - PURPOSE: To illustrate how a patient's previously undiagnosed obstructive sleep
      apnea was uncovered after administration of a spinal anesthetic with a high
      sensory blockade, and to discuss possible explanations for this occurrence and
      anesthetic implications. CLINICAL FEATURES: A 55-yr-old male presented for
      osteotomy and open reduction and internal fixation of his left femur secondary to
      malunion from a previous fracture. Past medical history consisted of
      hypertension, hypercholesterolemia, bipolar disorder, gastroesophageal reflux
      disease, and cluster headaches. A combined spinal-epidural technique was chosen.
      Isobaric bupivacaine 0.5% (15 mg), was provided for the spinal anesthetic, along
      with 1 mg iv midazolam for procedural sedation and 0.5 mg iv droperidol for mild
      nausea. Throughout the operation, many apneic events were noted, often with
      respiratory efforts. The patient was easily arousable during each event and would
      breathe normally until the next episode. Vital signs remained stable throughout.
      Postoperative respirology consultation was requested, and a sleep study revealed
      severe obstructive sleep apnea. The patient was subsequently started on
      continuous positive airway pressure with marked improvement in symptoms,
      including the cluster headaches. CONCLUSION: Recent literature suggests that high
      spinal blockade can result in altered levels of arousal by producing a de
      afferentation of peripheral proprioceptive and sensory stimuli necessary for
      maintaining an awake state. In patients predisposed to upper airway obstruction,
      decreasing the level of consciousness can result in airway obstruction as occurs
      during sleep in these patients. This serves to underline the importance of
      considering capnography for all cases utilizing a neuraxial anesthetic technique.

PMID- 16103392
TI  - Preemptive vessel dilator cricothyrotomy aids in the management of upper airway
      obstruction.
AB  - PURPOSE: Our objective was to demonstrate that preemptive vessel dilator
      cricothyrotomy may be useful when managing the patient with airway obstruction.
      METHODS: An Institutional Review Board approved retrospective study was
      undertaken in 88 patients for whom this technique was selected. The
      anesthesiologists and surgeons identified as authors were directly involved in
      the care of these patients. All vessel dilator cricothyrotomies were performed in
      the operating rooms of University Hospital, UAB, Medical Center. The patients
      selected for this airway management technique were afflicted with some type of
      supraglottic lesion, usually squamous cell carcinoma, which was obstructing their
      airways to an extent that complete airway obstruction during induction of
      anesthesia was a significant possibility. Prior to induction of anesthesia, the
      vessel dilator was inserted into the tracheal lumen through the cricothyroid
      membrane as described. Oxygenation was maintained with jet ventilation from a
      Sanders jetting device. Age, sex, weight, initial and lowest O(2) saturation,
      first recorded ETCO(2), blood pressure and duration of jet ventilation were
      recorded. RESULTS: The airways were successfully managed in all 88 patients with
      this technique. There were no deaths, and no postoperative hypoxic sequelae; also
      complications were minor. CONCLUSION: Vessel dilator cricothyrotomy as a
      preemptive procedure in the management of patients with significant supraglottic
      airway obstruction may be a useful addition to the anesthesiologists'
      armamentarium of airway management devices.

PMID- 16103393
TI  - A lesson learned.

PMID- 16103394
TI  - Subtle desaturation and perioperative methemoglobinemia. The need for continued
      vigilance.

PMID- 16103395
TI  - A malignant hyperthermia-like reaction in a six-month-old female with a 5q
      chromosomal deletion.

PMID- 16103396
TI  - Nerve stimulator guided pudendal nerve blocks.

PMID- 16103397
TI  - "Ventilator bellow standstill".

PMID- 16103398
TI  - 3.5-volt laryngoscope charger problem.

PMID- 16103399
TI  - Anesthetic implications of Reinke's edema of vocal cords.

PMID- 16103400
TI  - Avoiding exacerbation of the skills exodus.

PMID- 16103401
TI  - Dexmedetomidine is a useful adjunct for awake intubation.

PMID- 16103402
TI  - Successful first time use of the portable GlideScope videolaryngoscope in a
      patient with severe ankylosing spondylitis.

PMID- 16103403
TI  - Parker Flex-Tip tube for fibreoptic nasotracheal intubation in a case of lingual
      tonsil hypertrophy.

PMID- 16103404
TI  - Adopting ultrasound to facilitate central venous catheterization.

PMID- 16103405
TI  - "Conventional stylet" intubation--a misunderstood and misused concept.

PMID- 16103406
TI  - Production of type I interferons: plasmacytoid dendritic cells and beyond.
AB  - Plasmacytoid dendritic cells (pDCs) are specialized producers of type I
      interferons (IFNs) that respond to most viruses. Because of their antiviral
      activity and regulatory functions in innate and adaptive immunity, type I IFNs
      are important not only for antiviral resistance but also in other types of
      infections and in immune pathology. Here we discuss recent data that begin to
      reveal the unique molecular mechanisms underlying the remarkably rapid and
      efficient type I IFN production by pDCs.

PMID- 16103407
TI  - Possible role of human herpesvirus 8 in the lymphoproliferative disorders in
      common variable immunodeficiency.
AB  - Patients who have common variable immunodeficiency (CVID) and
      granulomatous/lymphocytic interstitial lung disease (GLILD) are at high risk for
      early mortality and B cell lymphomas. Infection with human herpes virus type 8
      (HHV8), a B cell lymphotrophic virus, is linked to lymphoproliferative disorders
      in people who have secondary immunodeficiencies. Therefore, we determined the
      prevalence of HHV8 infection in CVID patients with GLILD. Genomic DNA isolated
      from peripheral blood mononuclear cells was screened by nested- and real time
      quantitative PCR (QRT-PCR) for the presence of HHV8 genome. It was positive in
      6/9 CVID patients with GLILD (CVID-GLILD), 1/21 CVID patients without GLILD (CVID
      control), and no patients receiving intravenous gamma globulin (n = 13) or normal
      blood donors (n = 20). Immunohistochemistry (IHC) demonstrated expression of the
      latency-associated nuclear antigen-1 (LANA-1) in the biopsies of the lung, liver,
      and bone marrow of four patients with CVID-GLILD. One CVID-GLILD patient
      developed a B cell lymphoma during the course of the study. QRT-PCR demonstrated
      high copy number of HHV8 genome and IHC showed diffuse staining for LANA-1 in the
      malignant lymph node. HHV8 infection may be an important factor in the
      pathogenesis of the interstitial lung disease and lymphoproliferative disorders
      in patients with CVID.

PMID- 16103408
TI  - XBP-1 specifically promotes IgM synthesis and secretion, but is dispensable for
      degradation of glycoproteins in primary B cells.
AB  - Differentiation of B cells into plasma cells requires X-box binding protein-1
      (XBP-1). In the absence of XBP-1, B cells develop normally, but very little
      immunoglobulin is secreted. XBP-1 controls the expression of a large set of genes
      whose products participate in expansion of the endoplasmic reticulum (ER) and in
      protein trafficking. We define a new role for XBP-1 in exerting selective
      translational control over high and sustained levels of immunoglobulin M (IgM)
      synthesis. XBP-1(-/-) and XBP-1(+/+) primary B cells synthesize IgM at comparable
      levels at the onset of stimulation with lipopolysaccharide or CpG. However, later
      there is a profound depression in synthesis of IgM in XBP-1(-/-) B cells,
      notwithstanding similar levels of micromRNA. In marked contrast, lack of XBP-1
      does not affect synthesis and trafficking of other glycoproteins, or of
      immunoglobulin light chains. Contrary to expectation, degradation of proteins
      from the ER, using TCRalpha or US11-mediated degradation of class I major
      histocompatibility complex molecules as substrates, is normal in XBP-1(-/-) B
      cells. Furthermore, degradation of membrane mu was unaffected by enforced
      expression of XBP-1. We conclude that in primary B cells, the XBP-1 pathway
      promotes synthesis and secretion of IgM, but does not seem to be involved in the
      degradation of ER proteins, including that of mu chains themselves.

PMID- 16103409
TI  - 11beta-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of
      atherosclerosis in mice.
AB  - The enzyme 11beta-hydroxysteroid dehydrogenase (HSD) type 1 converts inactive
      cortisone into active cortisol in cells, thereby raising the effective
      glucocorticoid (GC) tone above serum levels. We report that pharmacologic
      inhibition of 11beta-HSD1 has a therapeutic effect in mouse models of metabolic
      syndrome. Administration of a selective, potent 11beta-HSD1 inhibitor lowered
      body weight, insulin, fasting glucose, triglycerides, and cholesterol in diet
      induced obese mice and lowered fasting glucose, insulin, glucagon, triglycerides,
      and free fatty acids, as well as improved glucose tolerance, in a mouse model of
      type 2 diabetes. Most importantly, inhibition of 11beta-HSD1 slowed plaque
      progression in a murine model of atherosclerosis, the key clinical sequela of
      metabolic syndrome. Mice with a targeted deletion of apolipoprotein E exhibited
      84% less accumulation of aortic total cholesterol, as well as lower serum
      cholesterol and triglycerides, when treated with an 11beta-HSD1 inhibitor. These
      data provide the first evidence that pharmacologic inhibition of intracellular GC
      activation can effectively treat atherosclerosis, the key clinical consequence of
      metabolic syndrome, in addition to its salutary effect on multiple aspects of the
      metabolic syndrome itself.

PMID- 16103410
TI  - Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal
      lymphopoietin transgene specifically in the skin.
AB  - The cytokine thymic stromal lymphopoietin (TSLP) has recently been implicated in
      the pathogenesis of atopic dermatitis (AD) and other allergic diseases in humans.
      To further characterize its role in this disease process, transgenic mice were
      generated that express a keratinocyte-specific, tetracycline-inducible TSLP
      transgene. Skin-specific overexpression of TSLP resulted in an AD-like phenotype,
      with the development of eczematous lesions containing inflammatory dermal
      cellular infiltrates, a dramatic increase in Th2 CD4+ T cells expressing
      cutaneous homing receptors, and elevated serum levels of IgE. These transgenic
      mice demonstrate that TSLP can initiate a cascade of allergic inflammation in the
      skin and provide a valuable animal model for future study of this common disease.

PMID- 16103411
TI  - Inducible DNA breaks in Ig S regions are dependent on AID and UNG.
AB  - Class switch recombination (CSR) occurs by an intrachromosomal deletion whereby
      the IgM constant region gene (Cmu) is replaced by a downstream constant region
      gene. This unique recombination event involves formation of double-strand breaks
      (DSBs) in immunoglobulin switch (S) regions, and requires activation-induced
      cytidine deaminase (AID), which converts cytosines to uracils. Repair of the
      uracils is proposed to lead to DNA breaks required for recombination. Uracil DNA
      glycosylase (UNG) is required for most CSR activity although its role is
      disputed. Here we use ligation-mediated PCR to detect DSBs in S regions in
      splenic B cells undergoing CSR. We find that the kinetics of DSB induction
      corresponds with AID expression, and that DSBs are AID- and UNG-dependent and
      occur preferentially at G:C basepairs in WRC/GYW AID hotspots. Our results
      indicate that AID attacks cytosines on both DNA strands, and staggered breaks are
      processed to blunt DSBs at the initiating ss break sites. We propose a model to
      explain the types of end-processing events observed.

PMID- 16103412
TI  - NanoStore: a concept for logistical improvements of compound handling in high
      throughput screening.
AB  - Small molecule screening, the systematic encounter of biology space with chemical
      space, has provoked the emergence of a whole industry that recreates itself by
      constant iterative improvements to this process. The authors describe an approach
      to tackle the problem for one of the most time-consuming steps in the execution
      of a screening campaign, namely, the reformatting of high-throughput screening
      test compounds from master plates to daughter assay plates used in the execution
      of the screen. Through an engineered storage procedure, they prepare plates ahead
      of the screening process with the respective compounds in a ready-to-use format.
      They show the biological inertness of the method and how it facilitates efficient
      recovery of compound activity. This uncoupling of normally interconnected
      processes provides time and compound savings, avoids repeated freeze-thaw cycles
      of compound solutions, and removes the problems associated with the DMSO
      sensitivity of certain assays types.

PMID- 16103413
TI  - Small interfering RNA and gene expression analysis using a multiplex branched DNA
      assay without RNA purification.
AB  - The authors have developed a novel multiplex detection system that quantitatively
      measures the expression level of 11 messenger RNAs (mRNAs) directly from cell
      lysates or tissue homogenates without RNA purification. The system incorporates
      branched DNA (bDNA) technology from Bayer and a multiplex bead array platform
      from Luminex. In this study, a 21-nt synthetic small interfering RNA (siRNA;
      specifically designed to knockdown interleukin-8 [IL-8] expression) was delivered
      into HeLa cells. Using the multiplex bDNA assay, gene expression levels were
      measured simultaneously from cell lysates for 11 genes. After treating the HeLa
      cells for 20 h with phorbol myristate acetate (PMA), IL-8 mRNA levels were
      induced by almost 50-fold; transfection with 30 nM IL-8-specific siRNA reduced
      the PMA-induced IL-8 mRNA by 80%. In addition, PMA induced mRNA expression in IL
      1alpha (3-fold) and IL-6 (4-fold); however, the IL-8 siRNA did not affect the
      expression of either of these 2 cytokine genes, indicating that the siRNA was
      selective for IL-8 mRNA expression. Three housekeeping genes' expression levels
      were measured under all conditions tested. The multiplex bDNA assay provides a
      powerful tool for quantitative multiplex gene expression analysis directly from
      cell lysates, which could be extremely valuable for conservation of rare or
      difficult-to-obtain samples.

PMID- 16103414
TI  - Screening mutant libraries of fungal laccases in the presence of organic
      solvents.
AB  - Reliable screening methods are being demanded by biocatalysts' engineers,
      especially when some features such as activity or stability are targets to
      improve under non-natural conditions (i.e., in the presence of organic solvents).
      The current work describes a protocol for the design of a fungal laccase
      expressed in Saccharomyces cerevisiae-highly active in organic cosolvents. A high
      throughput screening assay based on ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6
      sulfonic acid)) oxidation was validated. The stability of the ABTS radical cation
      was not significantly altered in the presence of acetonitrile, ethanol, or DMSO.
      With a coefficient of variance below 10% and a sensitivity limit of 15 pg
      laccase/microL, the assay was reproducible and sensitive. The expression system
      of Myceliophthora thermophila laccase variant T2 in S. cerevisiae was highly
      dependent on the presence of Cu2+. Copper concentration was limited up to 10
      microM CuSO4 where expression levels (approximately 14-18 mg/L) were acceptable
      without compromising the reliability of the assay. A mutant library was created
      by error-prone PCR with 1.1 to 3.5 mutations per kb. After only 1 generation of
      directed evolution, mutant 6C9 displayed about 3.5-fold higher activities than
      parent type in the presence of 20% acetonitrile or 30% ethanol. The method
      provided here should be generally useful to improve the activity of other redox
      enzymes in mixtures of water/cosolvents.

PMID- 16103415
TI  - Statistical analysis of systematic errors in high-throughput screening.
AB  - High-throughput screening (HTS) is an efficient technology for drug discovery. It
      allows for screening of more than 100,000 compounds a day per screen and requires
      effective procedures for quality control. The authors have developed a method for
      evaluating a background surface of an HTS assay; it can be used to correct raw
      HTS data. This correction is necessary to take into account systematic errors
      that may affect the procedure of hit selection. The described method allows one
      to analyze experimental HTS data and determine trends and local fluctuations of
      the corresponding background surfaces. For an assay with a large number of
      plates, the deviations of the background surface from a plane are caused by
      systematic errors. Their influence can be minimized by the subtraction of the
      systematic background from the raw data. Two experimental HTS assays from the
      ChemBank database are examined in this article. The systematic error present in
      these data was estimated and removed from them. It enabled the authors to correct
      the hit selection procedure for both assays.

PMID- 16103416
TI  - Evaluation of division-arrested cells for cell-based high-throughput screening
      and profiling.
AB  - Just-in-time cell supply for cell-based high-throughput screening (HTS) is
      frequently problematic. In addition to scheduling and logistical issues, quality
      issues and variability due to passage effect, cell cycle, or confluency
      contribute to day-to-day signal variability in the course of cell-based HTS
      campaigns. Cell division-arrest and cryopreservation technologies permit the use
      of cells as assay-ready reagents for HTS and other cell-based profiling and
      structure-activity studies. In this report, the authors compare division-arrested
      and dividing cells in 2 assay types that are dependent on movement of proteins
      within or through cell membranes: a receptor tyrosine kinase assay involving A431
      cells responsive to epidermal growth factor, and a secretion reporter assay,
      which measures secretion of a reporter gene, secreted alkaline phosphatase. In
      both assays, dividing and division-arrested cells yielded similar basal and
      maximal signals at a given cell density. Similar IC50s were obtained for
      reference inhibitors in each assay, type in both dividing and division-arrested
      cells. In addition, for the secretion reporter assay, when comparing IC50s
      obtained from 44 compounds randomly chosen from a primary screening hit list, the
      rank order of potency obtained from dividing cells and division-arrested cells
      was essentially identical. Furthermore, the results show that, under certain
      assay conditions, data generated using division-arrested cells are less variable
      than those generated using dividing cells. In summary, the results suggest that,
      in many cases, division-arrested cells can substitute for dividing cells and
      offer certain advantages for cell-based assays.

PMID- 16103417
TI  - A novel approach to determine water content in DMSO for a compound collection
      repository.
AB  - The quality of a corporate compound collection can be significantly affected by a
      complex combination of storage and operational processing factors. Water content
      in DMSO solutions is one factor that is of great interest as it can affect
      solubility, degradation, and freeze-thaw cycle parameters. To the authors'
      knowledge, this is the first report of using near-infrared (NIR) spectroscopy to
      assess water content in DMSO compound stock solutions within the common storage
      vessel format of polypropylene microtubes. The precision and accuracy of the NIR
      technique was benchmarked against a Karl Fisher titration method, and a
      correlation coefficient was determined to be 0.985 over a range of 1% to 10%
      water in DMSO by weight. The advantages of the NIR technique include accuracy,
      precision, speed, nondestructiveness, and the capability of assessing compounds
      under in situ storage conditions within microtubes. In this report, the authors
      demonstrate the accuracy and precision of using NIR to assess water content in
      DMSO solutions and present a case study to demonstrate the utility of the
      technique to aid in assessing a pharmaceutical compound collection.

PMID- 16103418
TI  - Development and application of a high-throughput screening assay for HIV-1
      integrase enzyme activities.
AB  - Integrase (IN) mediates the covalent insertion of the retroviral genome into its
      host chromosomal DNA. This enzymatic activity can be reconstituted in vitro with
      short DNA oligonucleotides, which mimic a single viral DNA end, and purified IN.
      Herein we report a highly efficient and sensitive high-throughput screen, HIV
      Integrase Target SRI Assay (HITS), for HIV-1 IN activity using 5' biotin-labeled
      DNA (5' BIO donor) and 3' digoxygenin-labeled DNA (3' DIG target). Following 3'
      processing of the 5' BIO donor, strand transfer proceeds with integration of the
      5' BIO donor into the 3' DIG target. Products were captured on a streptavidin
      coated microplate and the amount of DIG retained in the well was measured. The
      end point values, measured as absorbance, ranged from 0.9 to 1.5 for IN-mediated
      reactions as compared with background readings of 0.05 to 0.12. The Z factor for
      the assay ranged from 0.7 to 0.85. The assay was used to screen drugs in a high
      throughput format, and furthermore, we adapted the assay to study mechanistic
      questions regarding the integration process. For example, using variations of the
      assay format, we showed high preference of E strand of the long terminal repeat
      (LTR) viral DNA as a target strand compared with its complementary A strand. The
      E strand is the strand processed by IN. Furthermore, we explored the reported
      inhibitory effect of reverse transcriptase on integration.

PMID- 16103419
TI  - An automated multistep high-throughput screening assay for the identification of
      lead inhibitors of the inducible enzyme mPGES-1.
AB  - Prostaglandin E2 synthase (mPGES-1), the enzyme which catalyzes the synthesis of
      PGE2, is induced during the inflammatory response. For this reason, mPGES-1 could
      be a potential therapeutic target. A high-throughput screening assay was
      developed to identify potential inhibitors of mPGES-1. The assay consisted of a
      30-s mPGES-1 enzymatic reaction followed by the detection of PGE2 by enzyme
      immunoassay (EIA). The enzymatic reaction was performed in a batch mode because
      the instability of the substrate (10 min) limited the number of plates assayed
      within a working day. The detection of the product by EIA was performed on 3
      instruments requiring 14 different steps for complete automation. The authors
      describe here the optimization and implementation of a 2-part assay on a Thermo
      CRS robotic system. More than 315,000 compounds were tested, and a hit rate of
      0.84% was obtained for this assay. Although the entire assay required multiple
      steps, the assay was successfully miniaturized and automated for a high
      throughput screening campaign.

PMID- 16103420
TI  - Peptide binding identifies an ERalpha conformation that generates selective
      activity in multiple in vitro assays.
AB  - Drugs such as tamoxifen, which act at the estrogen receptor (ER), have very
      different in vitro and in vivo effects from those of the native hormone. Previous
      research has established that different ligands induce distinct conformational
      changes in the ER, thus affecting the interactions of the receptor with cell
      specific co-activating or co-repressing proteins (cofactors) and estrogen
      response elements (EREs), thus potentially driving differing biological effects.
      Affinity-selected peptides have been used to probe the conformational changes
      that occur within the ER upon binding various ligands. In this study, the authors
      characterize the ability of several peptides to be recruited to liganded ER under
      cellular conditions. Approximating ER conformation via recruitment of this
      peptide to the ER is concluded to be a better predictor of the agonist nature of
      an ER ligand under these different cellular contexts than is a canonical
      cotransfection transactivation assay.

PMID- 16103421
TI  - Further comparison of primary hit identification by different assay technologies
      and effects of assay measurement variability.
AB  - High-throughput screening (HTS) has grown rapidly in the past decade, with many
      advances in new assay formats, detection technologies, and laboratory automation.
      Recently, several studies have shown that the choice of assay technology used for
      the screening process is particularly important and can yield quite different
      primary screening outcomes. However, because the screening assays in these
      previous studies were performed in a single-point determination, it is not clear
      to what extent the difference observed in the screening results between different
      assay technologies is attributable to inherent assay variability and day-to-day
      measurement variation. To address this question, a nuclear receptor coactivator
      recruitment assay was carried out in 2 different assay formats, namely,
      AlphaScreen and time-resolved fluorescence resonance energy transfer, which
      probed the same biochemical binding events but with different detection
      technologies. For each assay format, 4 independent screening runs in a typical
      HTS setting were completed to evaluate the run-to-run screening variability.
      These multiple tests with 2 assay formats allow an unambiguous comparison between
      the discrepancies of different assay formats and the effects of the variability
      of assay and screening measurements on the screening outcomes. The results
      provide further support that the choice of assay format or technology is a
      critical factor in HTS assay development.

PMID- 16103422
TI  - A catalogue of human saliva proteins identified by free flow electrophoresis
      based peptide separation and tandem mass spectrometry.
AB  - Human saliva has great potential for clinical disease diagnostics. Constructing a
      comprehensive catalogue of saliva proteins using proteomic approaches is a
      necessary first step to identifying potential protein biomarkers of disease.
      However, because of the challenge presented in cataloguing saliva proteins with
      widely varying abundance, new proteomic approaches are needed. To this end, we
      used a newly developed approach coupling peptide separation using free flow
      electrophoresis with linear ion trap tandem mass spectrometry to identify
      proteins in whole human saliva. We identified 437 proteins with high confidence
      (false positive rate below 1%), producing the largest catalogue of proteins from
      a single saliva sample to date and providing new information on the composition
      and potential diagnostic utility of this fluid. The statistically validated,
      transparently presented, and annotated dataset provides a model for presenting
      large scale proteomic data of this type, which should facilitate better
      dissemination and easier comparisons of proteomic datasets from future studies in
      saliva.

PMID- 16103423
TI  - Complementing the genome with an "exposome": the outstanding challenge of
      environmental exposure measurement in molecular epidemiology.

PMID- 16103424
TI  - Introduction: what should we do now about H. pylori?

PMID- 16103425
TI  - The biology of Helicobacter pylori infection, a major risk factor for gastric
      adenocarcinoma.
AB  - Helicobacter pylori infection of the human stomach is the most important risk
      factor for development of gastric cancer. Whereas persistent viral infection
      leads to a number of cancers, H. pylori was the first bacteria linked to a human
      cancer. The exact mechanisms that lead to cancer induction are not clear, but
      study of the bacterial factors important for colonization and the host responses
      to the infection are starting to yield important clues.

PMID- 16103426
TI  - Helicobacter pylori and gastric cancer: what can be learned by studying the
      response of gastric epithelial cells to the infection?
AB  - The development of gastric adenocarcinoma is closely linked to chronic infection
      with the bacterial pathogen Helicobacter pylori. One Helicobacter-specific
      virulence factor in particular, the CagA protein, has emerged as a main effector
      molecule in the interaction of H. pylori with gastric epithelial cells and has
      been implicated in gastric carcinogenesis. This review highlights the latest
      insights that have been gained into the pathogenesis of the disease by
      transcriptional profiling approaches studying gene expression in normal gastric
      tissue and gastric cancer tissue from human biopsy material as well as animal
      models of Helicobacter infection. The potential role of CagA as a bacterial
      oncoprotein is also discussed.

PMID- 16103427
TI  - Etiology of gastric cancer: what is new?
AB  - Recent advances in understanding of risk factors for gastric cancer have focused
      attention on genetic polymorphisms in both the human host and in Helicobacter
      pylori. Variation in genes for cytokines such as interleukin-1beta and its
      receptor antagonist may allow identification of those individuals predisposed to
      mount an immune response that puts them at elevated risk for gastric cancer.
      Likewise, analysis of how genetic variation in the genome of H. pylori may
      modulate the action of virulence factors like CagA may prove useful in
      identification of persons for whom H. pylori eradication efforts would be most
      important. This review examines recent studies on interleukin-1beta polymorphisms
      and H. pylori CagA variation with respect to their modulation of risk for gastric
      cancer.

PMID- 16103428
TI  - Role of cytokine polymorphisms in the risk of distal gastric cancer development.
AB  - We review the current information concerning the role of cytokine polymorphisms
      and the risk of develop distal gastric cancer in different populations. We have
      included populations colonized with Helicobacter pylori as well as populations
      without colonization. We found that the study of polymorphisms alone seems
      insufficient to assess gastric cancer risk and it is necessary to examine
      environmental factors in different ethnic groups and geographic areas along with
      the study of H. pylori strains to define better the risk factors associated with
      distal gastric cancer.

PMID- 16103429
TI  - Trends in Helicobacter pylori infection and gastric cancer in Mexico.

PMID- 16103430
TI  - Host-environment interactions: their impact on progression from gastric
      inflammation to carcinogenesis and on development of new approaches to prevent
      and treat gastric cancer.
AB  - Revelation of the connection between Helicobacter pylori infection and gastric
      adenocarcinoma has prompted new investigations pertaining to its basic and
      clinical aspects. H. pylori-induced persistent and uncontrolled gastric
      inflammation nearly always precedes the development of cancer and is instrumental
      in initiating a multistep process leading to carcinogenesis. Despite initial
      optimism about the potential of combination anti-H. pylori therapy to ultimately
      eradicate gastric adenocarcinoma, recent investigations suggest its use should be
      targeted and tailored to a selected patient group considering the multifaceted
      role of H. pylori in disease and the disease heterogeneity of gastric
      adenocarcinoma. The clinical spectrum of H. pylori infection ranges from
      asymptomatic gastritis and peptic ulcer to gastric malignancies. The occurrence
      of one versus another is the result of differences in the magnitude of gastritis,
      and the current disease paradigm suggests gastric inflammation is common to all
      H. pylori-associated gastroduodenal diseases. Therefore, the host inflammatory
      responses to environmental triggers, rather than to bacteria or environmental
      factors per se, would dictate the variable outcomes of H. pylori infection.
      Putative factors that are expected to play an important role in stimulating
      inflammatory pathways and modulating the cross-talk between host and environment
      are age at the time of infection, environmental cofactors, H. pylori virulence,
      and host genetics. Elucidation of the intimate relationship between host
      environment interaction and gastric inflammation, although currently a formidable
      task, is essential in the development of new prevention and treatment strategies.
      Such knowledge might provide clues that allow more accurate prediction of
      variable outcomes of gastric inflammation and appropriate adjustment of treatment
      strategies, and might open up novel areas for studying gastric carcinogenesis.
      The evolving new technologies, such as microarray, proteomic, and functional
      genomic analyses, promise to shed new light on the immense complexity of the
      presumed host-environment interactions and will reveal more useful markers for
      the diagnosis and prognosis of gastric adenocarcinoma.

PMID- 16103431
TI  - The development of therapeutic and preventive vaccines for gastric cancer and
      Helicobacter pylori.
AB  - Gastric cancer is one of the most important worldwide public health problems.
      Convincing epidemiologic and etiologic associations have been made between the
      development of gastric cancer and infection with Helicobacter pylori. H. pylori
      not only has adapted to survive within the harsh environment of the stomach but
      also is able to modulate and avoid endogenous immune responses. The design and
      creation of efficacious vaccine strategies against H. pylori requires an
      understanding of the complex interactions that make up mucosal immunity. An
      effective vaccine strategy against H. pylori has the potential to affect
      significantly on population health worldwide.

PMID- 16103432
TI  - Vaccination as a method of preventing Helicobacter pylori-associated gastric
      cancer.

PMID- 16103433
TI  - Tobacco use and stomach cancer in Mizoram, India.
AB  - The incidence of stomach cancer in India is lower than that of any other country
      around the world. However, in Mizoram, one of the north-eastern state of India, a
      very high age-adjusted incidence of stomach cancer is recorded. A hospital-based
      case-control study was carried out to identify the influence of tobacco use on
      the risk of developing stomach cancer in Mizoram. Among the cases, the risk of
      stomach cancer was significantly elevated among current smokers [odds ratio (OR),
      2.3; 95% confidence interval (95% CI), 1.4-8.4] but not among ex-smokers. Higher
      risks were seen for meiziol (a local cigarette) smokers (OR, 2.2; 95% CI, 1.3
      9.3). The increased risk was apparent among subjects who had smoked for >or=30
      years. The increased risk was significant with 2-fold increase in risk among the
      subjects who smoked for >or=11 pack-years. The risk increased with increasing
      cumulative dose of tobacco smoked (mg). Tuibur (tobacco smoke-infused water),
      used mainly in Mizoram, was seemed to increased the risk of stomach cancer among
      current users in both univariate and multivariate models (OR, 2.1; 95% CI, 1.3
      3.1). Tobacco chewer alone (OR, 2.6; 95% CI, 1.1-4.2) showed significant risk.
      Tobacco use in any form [smoking and smokeless (tuibur and chewing)] increased
      the risk of stomach cancer in Mizoram independently after adjusting for
      confounding variables.

PMID- 16103434
TI  - Statins and cancer development.
AB  - There is epidemiologic evidence that the hydrophilic 3-hydroxy-3-methylglutaryl
      CoA (HMG-CoA) reductase inhibitor pravastatin increases the incidence of some
      extrahepatic cancers, although this finding has been attributed to chance. We
      hypothesize that pravastatin is able to promote the development of cancer by
      causing an induction of HMG-CoA reductase and, hence, mevalonate synthesis in
      extrahepatic tissues. We have shown that mevalonate, the product of HMG-CoA
      reductase, promotes the growth of breast cancer cells. Because there is no uptake
      of pravastatin by most extrahepatic cells, this statin will be unable to mitigate
      the increase in mevalonate synthesis in extrahepatic tissues that accompanies the
      decrease in circulating cholesterol caused by its inhibition of hepatic HMG-CoA
      reductase.

PMID- 16103435
TI  - Design options for molecular epidemiology research within cohort studies.
AB  - Past discussions of the relative strengths of nested case-control and case-cohort
      designs have not fully considered cohorts with stored biological samples in which
      biomarker analyses are planned. Issues related to biomarker analyses can affect
      an investigator's choice of design and the conduct of these two designs. The key
      issues identified are effects of analytic batch, long-term storage, and freeze
      thaw cycles on biomarkers. In comparison with the nested case-control design, the
      case-cohort design is less able to handle these challenges. Problems arise
      because most implementations of the case-cohort design do not allow for
      simultaneous evaluation of biomarkers in cases and reference group members, and
      there is no matching. By design, the nested case-control study controls for
      storage duration and the batching of biological samples from cases and controls
      is logistically simple. The allowance for matching also means that subjects can
      be matched on the number of freeze-thaw cycles experienced by the biological
      sample. However, the matching generates complex data sets that can be more
      difficult to analyze, and the costly biomarker data generated from the controls
      has few uses outside of testing the specific hypotheses of the study. In
      addition, because the same subject can serve as a control and a case, or multiple
      times as a control, biomarker analyses and sample batching can be more complex
      than initially anticipated. However, in total, of the two designs, the nested
      case-control study is better suited for studying biomarkers that can be
      influenced by analytic batch, long-term storage, and freeze-thaw cycles.

PMID- 16103436
TI  - Allergies and the risk of pancreatic cancer: a meta-analysis with review of
      epidemiology and biological mechanisms.
AB  - Previous reports suggest that allergic disorders may protect against various
      types of cancer, but the association between history of allergy and pancreatic
      cancer risk has not been well studied. We did a systematic review and meta
      analysis of published studies to evaluate the association of any type, and
      specific types, of allergy and the risk of pancreatic cancer. We did a
      comprehensive literature search using MEDLINE, PUBMED, and the ISI Web of Science
      databases to identify potential relevant case-control and cohort studies. Pooled
      relative risks (RR) and 95% confidence intervals (95% CI) were calculated using
      the fixed- and random-effects model. Fourteen population-based studies (4 cohort
      and 10 case-control studies) with a total of 3,040 pancreatic cancer cases
      fulfilled our inclusion criteria. A history of allergy was associated with a
      reduced risk of pancreatic cancer (RR, 0.82; 95% CI, 0.68-0.99). The risk
      reduction was stronger for allergies related to atopy (RR, 0.71; 95% CI, 0.64
      0.80), but not for asthma (RR, 1.01; 95% CI, 0.77-1.31). There was no association
      between allergies related to food or drugs and pancreatic cancer (RR, 1.08; 95%
      CI, 0.74-1.58). Overall, there was no evidence of publication bias. Allergies, in
      particular those related to atopy, seem to be associated with a decreased risk of
      pancreatic cancer. The hyperactive immune system of allergic individuals may,
      therefore, in some way lead to increased surveillance and protect against
      pancreatic cancer development.

PMID- 16103437
TI  - Further enhanced monitoring of cancer patient survival by stage-adjusted period
      analysis.
AB  - Monitoring progress in cancer patient survival is an important task of population
      based cancer registration. Period analysis has been shown to provide more up-to
      date estimates of cancer patient survival than traditional methods of survival
      analysis. However, even period estimates may disclose recent improvements in long
      term survival with some delay as they are still partly based on the survival
      experience of patients diagnosed years ago. If these patients had a less
      favorable stage distribution than the patients diagnosed in a more recent
      calendar period (e.g., due to progress in early detection), period estimates may
      underestimate long-term survival for patients diagnosed in that period. This
      particular source of potential underestimation can be overcome by adjustment of
      the stage distribution of all patients included in period analysis to the stage
      distribution of the patients diagnosed in the period of interest. The principle,
      application, and use of stage adjustment of period survival estimates are
      illustrated with 5- and 10-year relative survival estimates of patients diagnosed
      with breast cancer and followed with respect to survival in the United States
      between 1973 and 2001, using data of the Surveillance, Epidemiology, and End
      Results Program of the National Cancer Institute. We show that stage adjustment
      may often further enhance the benefits of period analysis for deriving up-to-date
      cancer survival estimates.

PMID- 16103438
TI  - Increased risk of cancer among siblings of long-term childhood cancer survivors:
      a report from the childhood cancer survivor study.
AB  - We determined risk of cancer among first-degree relatives of 5-year survivors of
      childhood leukemia, lymphoma, central nervous system tumors, sarcomas, Wilms'
      tumor, and neuroblastoma. Subjects were 13,703 participants in the Childhood
      Cancer Survivor Study. Family history was collected on 56,759 first-degree
      relatives using a self-reported questionnaire. Incidence was compared with age-
      and sex-specific rates using the U.S. Surveillance, Epidemiology and End Results
      program. Siblings of the survivors had an increased risk of cancer [standardized
      incidence ratio (SIR), 1.5; 95% confidence interval (95% CI), 1.35-1.7]. Risk was
      elevated for siblings of probands of leukemia (SIR, 1.3; 95% CI, 1.0-1.6),
      Hodgkin's disease (SIR, 1.5; 95% CI, 1.2-1.9), non-Hodgkin's lymphoma (SIR, 1.8;
      95% CI, 1.3-2.5), Wilms' tumor (SIR, 1.9; 95% CI, 1.2-3.2), soft tissue sarcoma
      (SIR, 1.5; 95% CI, 1.0-2.2), and bone tumors (SIR, 1.6; 95% CI, 1.2-2.2). Cancer
      risk was elevated in siblings (SIR, 2.4; 95% CI, 1.5-3.7) and offspring (SIR,
      15.0; 95% CI, 5.3-42.9) of probands with second malignant neoplasms (SMN)
      compared with relatives of probands without SMNs. Siblings of probands with
      leukemia, Hodgkin's disease, neuroblastoma, and Wilms' tumor had elevated risks
      for the same malignancies. Parents had no increased risk (fathers' SIR, 0.7; 95%
      CI, 0.7-0.8; mothers' SIR, 0.9; 95% CI, 0.9-1.0). Seventy percent of siblings'
      cancers developed in adulthood. These findings suggest that familial cancer
      syndromes may be revealed as this cohort and family members age and with accrual
      of more offspring and subjects with SMNs.

PMID- 16103439
TI  - Ethnic difference in daycare attendance, early infections, and risk of childhood
      acute lymphoblastic leukemia.
AB  - A role for infectious agents has been proposed in the etiology of childhood acute
      lymphoblastic leukemia (ALL), particularly for common ALL (c-ALL; ALL diagnosed
      in children ages 2-5 years and expressing CD10 and CD19 surface antigens). We
      evaluated the possible etiologic role of daycare attendance (a proxy measure for
      exposure to infectious agents) and infections during infancy in the Northern
      California Childhood Leukemia Study. A total of 294 incident ALL cases (ages 1-14
      years) and 376 individually matched controls were included in this analysis. In
      non-Hispanic White children, daycare attendance measured by child-hours was
      associated with a significantly reduced risk of ALL. Compared with children who
      did not attend any daycare, the odds ratio (OR) for those who had >5,000 child
      hours during infancy was 0.42 [95% confidence interval (95% CI), 0.18-0.99] for
      ALL and 0.33 (95% CI, 0.11-1.01) for c-ALL. Test for trend is also significant,
      which supports a dose-response relationship. The magnitude of effect associated
      with the same number of child-hours was stronger for daycare attendance during
      infancy than for daycare attendance before diagnosis. In addition, self-reported
      ear infection during infancy was associated with a significantly reduced risk of
      c-ALL (OR, 0.32; 95% CI, 0.14-0.74) in non-Hispanic White children. In Hispanic
      children, no association was observed among daycare attendance, early infections,
      and risk of childhood ALL or c-ALL. These results offer indirect yet strong
      support for the infectious disease hypothesis in the etiology of ALL in non
      Hispanic White children and highlight an important ethnic difference.

PMID- 16103440
TI  - Maternal diet and acute lymphoblastic leukemia in young children.
AB  - Because leukemia clone-specific chromosomal abnormalities are present at birth in
      children who later develop leukemia, it has been hypothesized that maternal
      factors, including nutrition during pregnancy, might affect the risk of acute
      lymphoblastic leukemia (ALL) among young children. We have evaluated this
      hypothesis in a nationwide case-control study of ALL among children ages 12 to 59
      months in Greece. Children (n=131) with ALL were gender and age matched to
      control children (n=131) hospitalized for minor conditions between 1999 and 2003.
      The mothers of the children were interviewed in person by trained interviewers
      who used an extensive food frequency questionnaire addressing diet during the
      index pregnancy. The analysis was done by modeling the data through conditional
      logistic regression, also controlling for total energy intake and possible
      confounding factors. Odds ratios (OR) and 95% confidence intervals (95% CI) were
      expressed per quintile increase of maternal intake during pregnancy of the
      specified food group. The risk of ALL in the offspring was lower with increased
      maternal intake of fruits (OR, 0.72; 95% CI, 0.57-0.91), vegetables (OR, 0.76;
      95% CI, 0.60-0.95), and fish and seafood (OR, 0.72; 95% CI, 0.59-0.89) and higher
      with increased maternal intake of sugars and syrups (OR, 1.32; 95% CI, 1.05-1.67)
      and meat and meat products (OR, 1.25; 95% CI, 1.00-1.57). Children of women who
      tend to consume during their pregnancies what is currently considered to be a
      healthy diet maybe at lower risk of ALL.

PMID- 16103441
TI  - Season, sun, sex, and cervical cancer.
AB  - INTRODUCTION: Sunlight's UV B component, a known cellular immunosupressant,
      carcinogen, and activator of viral infections, is generally seasonally available.
      Venereal human papillomavirus (HPV) transmission, at least in part, causes
      cervical cancer. We have previously inspected the monthly rates of venereal HPV
      infection and sunlight fluency in Southern Holland over 16 consecutive years.
      Both peak in August with at least 2-fold seasonality. The amount of available
      sunlight and the rate of Papanicolaou (Pap) smear screen-detected HPV are
      positively correlated. We now investigate whether premalignant and malignant
      cervical epithelial changes are also seasonal and related to seasonal sunlight
      fluency. METHODS: We have studied >900,000 consecutive, serially independent,
      interpretable screening Pap smears obtained by a single cervical cancer screening
      laboratory in Leiden, Holland, during a continuous 16-year span from 1983 through
      1998. The average monthly rates of premalignant and malignant epithelial change
      were inspected and the annual patterns contrasted to the annual pattern of
      sunlight fluency at this global location and to monthly average HPV infection
      rate. Because HPV is venereally transmitted, Dutch seasonal sexual behavior was
      evaluated by assessment of the annual pattern of Dutch conception frequency as a
      competing cause for cervical cancer seasonality. RESULTS: (a) Twice as many
      premalignant and malignant epithelial changes were found among Pap smears
      obtained in the summer months, with an August peak concurrent with
      histopathologic evidence of HPV infection and sunlight fluency in Southern
      Holland. (b) Monthly sunlight fluency is correlated positively with both the
      monthly rates of Pap smear-detected cervical epithelial dysplasia and
      carcinomatous histopathology, as well as HPV. (c) Conception frequency, in this
      location, peaks in Spring not summer, and has a 4.8% annual amplitude.
      CONCLUSIONS: (a) Cervical epithelial HPV infection and HPV-induced cervical
      epithelial dysplasia and carcinomatous change may each be novel sun exposure
      risks and thereby behaviorably avoidable. (b) Because screening Pap smears
      uncover many abnormalities that resolve spontaneously (false positives), these
      data may argue for screening and follow-up Pap smear examinations in seasons
      other than summer in the Northern Hemisphere, to diminish the false-positive
      smear rate. Global data are available to confirm and further test each of these
      conclusions.

PMID- 16103442
TI  - Correlation of human papillomavirus type 16 and human papillomavirus type 18 e7
      messenger RNA levels with degree of cervical dysplasia.
AB  - Infection with certain types of human papillomavirus (HPV) is a necessary event
      in the development of cervical carcinoma; however, not all women who become
      infected with HPV will progress to cancer. Much is known about the molecular
      influence of HPV E6 and E7 proteins on the malignant transformation. Little is
      known about the additional factors needed to drive the process. Quantitative real
      time PCR was used to quantitate mRNA expression of the E7 gene in women
      exhibiting normal epithelium, low-grade squamous intraepithelial lesions (LSIL),
      and high-grade squamous intraepithelial lesions (HSIL). Prevalence of mRNA
      transcripts was lower among normal women (27%) than for women with LSIL (40%) and
      HSIL (37%). Mean levels ranged from 2.0 (ln scale per 20 ng cDNA) among normal
      women to 4.2 among those with HSIL, with a significant trend (P=0.008). This
      trend was only significant for HPV 18 transcripts if separately analyzed by HPV
      type. The transcriptional activity of HPV 18 is higher than that of HPV 16 and
      increases with increasing level of dysplasia. This is in concert with the
      findings of other studies, and reinforces the notion that HPV 18 is a more
      aggressive viral type. Real-time PCR of viral transcripts could provide a more
      efficient method to analyze the oncogenic potential within cells from a cervical
      swab, thus providing a way to better screen women who may progress to higher
      grade lesions or invasive carcinoma from those who will spontaneously regress.

PMID- 16103443
TI  - A phase I study of indole-3-carbinol in women: tolerability and effects.
AB  - We completed a phase I trial of indole-3-carbinol (I3C) in 17 women (1
      postmenopausal and 16 premenopausal) from a high-risk breast cancer cohort. After
      a 4-week placebo run-in period, subjects ingested 400 mg I3C daily for 4 weeks
      followed by a 4-week period of 800 mg I3C daily. These chronic doses were
      tolerated well by all subjects. Hormonal variables were measured near the end of
      the placebo and dosing periods, including determination of the urinary 2
      hydroxyestrone/16alpha-hydroxyestrone ratio. Measurements were made during the
      follicular phase for premenopausal women. Serum estradiol, progesterone,
      luteinizing hormone, follicle-stimulating hormone, and sex hormone binding
      globulin showed no significant changes in response to I3C. Caffeine was used to
      probe for cytochrome P450 1A2 (CYP1A2), N-acetyltransferase-2 (NAT-2), and
      xanthine oxidase. Comparing the results from the placebo and the 800 mg daily
      dose period, CYP1A2 was elevated by I3C in 94% of the subjects, with a mean
      increase of 4.1-fold. In subjects with high NAT-2 activities, these were
      decreased to 11% by I3C administration but not altered if NAT-2 activity was
      initially low. Xanthine oxidase was not affected. Lymphocyte glutathione S
      transferase activity was increased by 69% in response to I3C. The apparent
      induction of CYP1A2 was mirrored by a 66% increase in the urinary 2
      hydroxyestrone/16alpha-hydroxyestrone ratio in response to I3C. The maximal
      increase was observed with the 400 mg daily dose of I3C, with no further increase
      found at 800 mg daily. If the ratio of hydroxylated estrone metabolites is a
      biomarker for chemoprevention, as suggested, then 400 mg I3C daily will elicit a
      maximal protective effect.

PMID- 16103444
TI  - Expression of nucleotide excision repair proteins in lymphocytes as a marker of
      susceptibility to squamous cell carcinomas of the head and neck.
AB  - The transcript levels of nucleotide excision repair (NER) genes were shown to be
      associated with risk of squamous cell carcinomas of the head and neck (SCCHN).
      However, this association may be biased, because the transcript level does not
      necessarily reflect the level of protein expression. To address this issue, we
      did a pilot study to test the hypothesis that the expression of six core NER
      proteins is associated with risk of SCCHN. We obtained cultured lymphocytes from
      57 patients with newly diagnosed SCCHN patients and 63 cancer-free controls. We
      transfected some of the lymphocytes with both damaged and undamaged plasmid DNA
      and quantified NER protein levels in these lymphocytes using a reverse-phase
      protein microarray. The relative NER protein levels in the 63 controls were
      highly correlated with each other (P<0.001 for all). Compared with the controls,
      the cases had lower expression levels for all the NER proteins, particularly XPC
      and XPF, which were reduced by about 25% (P<0.01). When we used the median
      expression levels of the NER proteins in the controls as cutoff values, we found
      that a significantly increased risk of SCCHN was associated with low expression
      of XPA [odds ratio (OR), 2.99; 95% confidence interval (CI), 1.22-7.47], XPC (OR,
      2.46; 95% CI, 1.04-5.87), XPD (OR, 3.02; 95% CI, 1.18-7.76), and XPF (OR, 5.29;
      95% CI, 2.01-13.9), but not ERCC1 and XPG, after adjustment for age, sex,
      ethnicity, smoking, alcohol use, and sample storage time. In a multivariate
      logistic regression model that included all covariates and NER proteins, however,
      only low expression of XPF remained a significant risk factor for SCCHN (OR,
      11.5; 95% CI, 2.32-56.6). These results suggest that XPF may be a crucial rate
      limiting factor in DNA repair and that the reverse-protein microarray assay may
      be a useful tool for measuring protein markers of susceptibility to cancer.

PMID- 16103445
TI  - Alcohol, ALDH2, and esophageal cancer: a meta-analysis which illustrates the
      potentials and limitations of a Mendelian randomization approach.
AB  - Mendelian randomization, the use of common polymorphisms as surrogates for
      measuring exposure levels in epidemiologic studies, provides one method of
      assessing the causal nature of some environmental exposures. This can be
      illustrated by looking at the association between the ALDH2 polymorphism and
      esophageal cancer. Alcohol drinking is considered a risk factor for esophageal
      cancer, and exposure to high levels of acetaldehyde, the principal metabolite of
      alcohol, may be responsible for the increased cancer risk. The ability to
      metabolize acetaldehyde is encoded by the ALDH2 gene, which is polymorphic in
      some populations. The ALDH2*2 allele produces an inactive protein subunit, which
      is unable to metabolize acetaldehyde. An individual's genotype at this locus may
      influence their esophageal cancer risk through two mechanisms, first through
      influencing alcohol intake and second through influencing acetaldehyde levels. We
      have carried out a meta-analysis of studies looking at the ALDH2 genotype and
      esophageal cancer and found that risk was reduced among *2*2 homozygotes [odds
      ratio (OR), 0.36; 95% confidence interval (95% CI), 0.16-0.80] and increased
      among heterozygotes (OR, 3.19; 95% CI, 1.86-5.47) relative to *1*1 homozygotes.
      This provides strong evidence that alcohol intake increases the risk of
      esophageal cancer and individuals whose genotype results in markedly lower
      intake, because they have an adverse reaction to alcohol are thus protected. This
      meta-analysis also provides evidence that acetaldehyde plays a carcinogenic role
      in esophageal cancer. The two different processes operating as a result of the
      ALDH2 genotype have implications for the interpretation of studies using the
      Mendelian randomization paradigm.

PMID- 16103446
TI  - Carbonyl reductase expression and its clinical significance in non-small-cell
      lung cancer.
AB  - Carbonyl reductase (CBR) is a cytosolic NADPH-dependent oxidoreductase
      metabolizing prostaglandins, steroids, quinines, and anthracycline antibiotics.
      Many experimental studies have shown that CBR plays important roles in the
      regulation of tumor progression, but clinical significance of CBR status remains
      unclear. Thus, we conducted a retrospective study on CBR mRNA expression in lung
      cancer. Tumor tissues obtained from 59 non-small-cell lung cancer patients were
      analyzed by quantitative real-time reverse transcription-PCR assay to reveal
      clinical significance of CBR expression. Angiogenesis was measured
      immunohistochemically as intratumoral microvessel density (IMVD) using anti-CD34
      monoclonal antibody CD34-IMVD) and anti-CD105 monoclonal antibody (CD105-IMVD).
      CBR mRNA expression was significantly reduced along with progression of primary
      tumors (the mean CBR mRNA/GAPDH mRNA, 3.288x10(-2) for pT1, 1.628x10(-2) for pT2,
      and 1.175x10(-2) for pT3-4 disease, respectively; P=0.02). Moreover, CBR mRNA
      expression in tumor with nodal involvement seemed to be reduced as compared with
      that in tumor without nodal involvement (the mean CBR mRNA/GAPDH mRNA, 1.446x10(
      2) and 2.531x10(-2), respectively), whereas the difference did not reach a
      statistical significance (P=0.09). The mean CD105-IMVD for CBR-high tumor was
      59.2, which was significantly lower than that for CBR-low tumor (130.6, P=0.02),
      whereas no significant difference between the mean CD34-IMVDs for CBR-high tumor
      and CBR-low tumor was found. The 5-year survival rate of CBR-high patients was
      68.3%, significantly higher than that of CBR-low patients (36.5%; P=0.03). A
      multivariate analysis confirmed that CBR-high expression was a significant factor
      to predict a favorable prognosis (P=0.04; relative risk, 0.39; 95% confidence
      interval, 0.16-0.98). Expression of CBR mRNA was a significant prognostic factor
      in non-small-cell lung cancer and was inversely associated with tumor progression
      and angiogenesis.

PMID- 16103447
TI  - Social and behavioral correlates of cigarette smoking among mid-Atlantic Latino
      primary care patients.
AB  - Tobacco use is the leading preventable cause of death for the U.S. Hispanic
      population. The goal of this study was to identify social and behavioral
      correlates of smoking behavior among urban, multiethnic Latino primary care
      patients seen in community clinics. Spanish-language interviews were completed
      with 141 current smokers and 158 former and nonsmokers. Twenty countries of
      origin were represented. Eighty-three percent of participants were from Central
      or South America and 71% spoke primarily Spanish. Current smokers were more
      likely than nonsmokers or former smokers to originate from South America (38%
      versus 26%) and to be single (63% versus 42%). Current smokers also were more
      likely to use alcohol on a regular basis (59% versus 31%) and to experience daily
      symptoms of depression (29% versus 19%). Logistic regression analysis suggested a
      moderating effect of depression on the relationship between alcohol use and
      smoking, such that current users of alcohol who reported depression were more
      likely to smoke (82%) than were current users of alcohol who did not report
      depression (56%). As both social and behavioral factors were uniquely associated
      with smoking, country of origin, marital status, and comorbid alcohol use and
      depression should be considered in designing and implementing tobacco control
      interventions targeted to this community.

PMID- 16103448
TI  - The 1944-1945 Dutch famine and subsequent overall cancer incidence.
AB  - Caloric restriction seems to be the most potent dietary intervention to protect
      against a variety of cancers in animals. We investigated whether overall cancer
      risk is affected in humans after exposure to a brief famine, followed by a period
      of abundance. We used data of approximately 15,000 women who were exposed at
      various degrees to the 1944-1945 Dutch famine at ages between 2 and 33 years.
      Between 1983 and 1986, these women were asked about their individual experiences
      of famine exposure ("absent," "moderate," or "severe exposure"). During follow-up
      until January 2000, 1,602 new cancer cases were identified by the regional cancer
      registry. We assessed the relation between famine and total cancer risk by
      weighted Cox regression models, in which a 15% random sample was used to
      represent person-years lived in the entire cohort. In these models, we adjusted
      for potential confounders. Overall cancer risk was increased in women having been
      severely famine exposed compared with women having been unexposed (hazard ratio,
      1.25; 95% confidence interval, 1.01-1.55). Exclusion of breast cancer cases from
      our analyses showed that this increase in risk was largely driven by the
      previously reported increase in breast cancer risk: women who were severely
      exposed to the famine were at a 1.12 (95% confidence interval, 0.87-1.43) times
      increased risk of non-breast cancer compared with the unexposed. In conclusion,
      we found no indications that this brief famine has affected overall cancer risk,
      exclusive of breast cancer. Counteracting increased caloric intake following the
      famine, however, may have obscured any relation.

PMID- 16103449
TI  - Significant difference in the trends of female breast cancer incidence between
      Taiwanese and Caucasian Americans: implications from age-period-cohort analysis.
AB  - Female invasive breast cancer (FIBC) in Taiwan is characterized by a striking
      recent increase of incidence and a relatively young median age (45-49 years) at
      diagnosis. The Westernization of lifestyle that is increasingly affecting younger
      generations of Taiwanese may have an important impact on this change. We compared
      epidemiologic data on FIBC in Taiwanese obtained from the Taiwan Cancer Registry
      with data for Caucasian Americans obtained from the database of the Surveillance,
      Epidemiology, and End Results Program for the period from 1980 to 1999. Age
      specific incidence rates of FIBC were plotted by calendar year at diagnosis and
      by birth cohort for both populations. The individual effects of time period and
      birth cohort on the incidence trends of FIBC in both populations were evaluated
      using the age-period-cohort analysis. The incidence rate of FIBC was continuously
      increased in Taiwanese throughout the past 2 decades, whereas the increase of
      incidence was slowing down in Caucasian Americans. The incidence rates in
      Taiwanese women born after the 1960s were approaching that of Caucasian
      Americans. The age-period-cohort analysis showed a much stronger birth cohort
      effect on the incidence trend of FIBC in Taiwanese than in Caucasian Americans.
      This strong birth cohort effect corresponded to the Westernization of lifestyle
      in Taiwan since 1960. These findings indicate that a continued shift in the
      incidence and age distribution pattern of FIBC in Taiwanese toward that of
      Caucasian Americans should be anticipated.

PMID- 16103450
TI  - Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer.
AB  - Several lines of evidence suggest that vitamin D may reduce incidence of breast
      cancer, but few epidemiologic studies have addressed the relation of plasma
      vitamin D metabolites to the risk of this disease. We prospectively examined the
      relationship between plasma levels of 25-hydroxyvitamin D [25(OH)D] and 1,25
      dihydroxyvitamin D [1,25(OH)2D] and risk of breast cancer in a case-control study
      nested within the Nurses' Health Study cohort. Blood samples were collected from
      study participants in 1989-1990. Breast cancer cases developing between blood
      collection and June 1, 1996, were matched to cancer-free controls on the basis of
      age, menopausal status, and other factors. Stored plasma samples from 701 cases
      and 724 controls were available for metabolite analysis. Cases had a lower mean
      25(OH)D level than controls (P=0.01), but mean 1,25(OH)2D levels were similar
      (P=0.49). High levels of both metabolites were associated with a nonsignificant
      lower risk of breast cancer. Women in the highest quintile of 25(OH)D had a
      relative risk of 0.73 (95% confidence interval=0.49-1.07; Ptrend=0.06) compared
      with those in the lowest quintile. For 1,25(OH)2D, the comparable relative risk
      was 0.76 (95% confidence interval=0.52-1.11; Ptrend=0.39). For both metabolites,
      the association was stronger in women ages 60 years and older, but results were
      not statistically significant. Our findings suggest that high levels of 25(OH)D,
      and perhaps 1,25(OH)2D, may be modestly associated with reduced risk of breast
      cancer.

PMID- 16103451
TI  - Estrogen metabolism-related genes and breast cancer risk: the multiethnic cohort
      study.
AB  - Common polymorphisms in genes that affect estrogen levels may be associated with
      breast cancer risk. We investigated the associations between breast cancer and
      sequence variants in several genes in the estradiol/estrone metabolism pathway
      (CYP1A1*2A, CYP1A2*1F, CYP1B1 Leu432Val, CYP3A4*1B, COMT Val158Met,
      SULT1A1Arg213His) as well as the Arg554Lys variant in AHR (a transcription factor
      for CYP1A1, CYP1A2, and CYP1B1) in a case-control study of 1,339 breast cancer
      cases and 1,370 controls nested in the Multiethnic Cohort Study. The Multiethnic
      Cohort Study is a large prospective study of men and predominantly postmenopausal
      women of Japanese, White, African American, Latino, and Native Hawaiian ancestry,
      residing in Hawaii and Los Angeles. We found no association between breast cancer
      and these polymorphisms, except for CYP1A2*1F which was inversely associated with
      risk. The odds ratio (95% confidence interval) for the AA, AC, and CC genotype
      was 1.0, 0.9 (0.7-1.0), and 0.7 (0.5-1.0), respectively (P for gene dosage
      effect=0.03). This association seemed somewhat stronger for estrogen receptor
      (ER)/progesterone receptor (PR)-negative tumors than for ER/PR-positive tumors,
      and no statistically significant interaction with estrogen-related risk factors
      was detected. The findings provide no evidence for a role of COMT Val58Met,
      CYP1A1*2A, CYP3A4*1B, CYP1B1 Leu432Val, SULT1A1 Arg213His, and AHR Arg554Lys in
      breast cancer etiology. They also provide support for an inverse association
      between CYP1A2*1F and breast cancer, which is consistent with the observation of
      lower circulating estrogen levels in premenopausal women with the CC genotype in
      a previous study.

PMID- 16103452
TI  - Folate intake and risk of breast cancer characterized by hormone receptor status.
AB  - Folate plays an important role in DNA methylation, and aberrant methylation of
      the estrogen receptor (ER) gene may be related to the loss of ER gene expression
      in breast tumors. Thus, deficient folate status has been hypothesized to be
      associated primarily with ER gene-negative breast tumors, but data relating
      folate intake to breast cancer risk according to ER status are sparse. We
      conducted a prospective cohort analysis of folate intake among 88,744 women in
      the Nurses' Health Study who completed a food frequency questionnaire in 1980 and
      every 2 to 4 years thereafter. During 20 years of follow-up, 2,812 ER+ and 985 ER
      invasive breast cancer cases were documented. Higher total folate intake was
      significantly associated with lower risk of developing ER- but not ER+ breast
      cancer; the multivariable relative risks (RR) and 95% confidence intervals (95%
      CI) comparing the highest to the lowest quintile were 0.81 (0.66-0.99) for ER-
      tumors and 1.00 (0.89-1.14) for ER+ tumors. The inverse association between total
      folate intake and ER- breast cancer was mainly present among women consuming at
      least 15 g/d of alcohol (multivariable RR, 0.46; 95% CI,=0.25-0.86; top versus
      bottom quintile). These findings support the hypothesis that higher folate intake
      reduces the risk of developing ER- breast cancer. Ensuring adequate folate intake
      seems particularly important for women at higher risk of breast cancer because of
      alcohol consumption.

PMID- 16103453
TI  - Body mass and mortality after breast cancer diagnosis.
AB  - Obesity is an established risk factor for some breast cancers, but less is known
      about its effect on breast cancer prognosis. Understanding this relationship is
      important, given the increasing number of women diagnosed with breast cancer and
      the growing prevalence of obesity. We conducted a cohort analysis of 3,924 women
      ages 20 to 54 with incident breast cancer enrolled between 1980 and 1982 in the
      Cancer and Steroid Hormone study, a case-control study. Interview data were
      linked to survival information from the Surveillance, Epidemiology, and End
      Results Program. We used proportional hazards models to examine the relationship
      between breast cancer mortality and adult body mass index (BMI; calculated using
      usual adult weight), BMI at age 18, and weight change from age 18 to adulthood.
      Hazard ratios (HR) were adjusted for cancer stage and other factors. During a
      median follow-up of 14.6 years, 1,347 women died of breast cancer. Obese women
      (adult BMI>or=30.00) were significantly more likely than lean women
      (BMI<or=22.99) to die of breast cancer [HR, 1.34; 95% confidence interval (CI),
      1.09-1.65]. Women with BMIs of 25.00-29.99 (HR, 1.25; 95% CI, 1.08-1.44) or 23.00
      24.99 (HR, 1.20; 95% CI, 1.04-1.39) also had higher breast cancer mortality (P
      for trend <0.0001). BMI at age 18 and weight change were not associated with
      breast cancer mortality independently of other factors. Obesity could be a
      preventable risk factor for death among breast cancer patients. Further study is
      needed to determine how these findings might affect recommendations to reduce
      breast cancer mortality.

PMID- 16103454
TI  - Etiologic and other factors predicting nevus-associated cutaneous malignant
      melanoma.
AB  - Cutaneous malignant melanomas with histologic evidence of an associated nevus
      (N+) may have a different risk factor profile from that of melanomas without it
      (N-). To address this question, a case-only analysis of 932 people with cutaneous
      malignant melanoma was done to identify etiologic and other factors associated
      with N+ melanoma. Evidence of an associated nevus was found in 36% of melanomas.
      N+ melanomas were thinner (Ptrend=0.0009) and more likely to be of the
      superficial spreading type than other types of melanoma. Subjects with N+
      melanomas were younger (Ptrend<0.0001) and reported a higher nevus density on
      their skin than subjects with N- melanomas [odds ratio (OR), 3.1; 95% confidence
      interval (CI), 1.6-6.0, for high nevus density versus no nevi]. Indicators of
      high accumulated sun exposure were less prevalent among subjects with N+
      melanomas (OR, 0.3; 95% CI, 0.2-0.4, for melanoma location on the head and neck
      versus location on trunk; OR, 0.2; 95% CI, 0.1-0.4, for severe solar elastosis
      adjacent to the melanoma versus no elastosis; OR, 0.2; 95% CI, 0.1-0.4, for
      lentigo maligna melanoma subtype versus superficial spreading subtype). With the
      exception of solar elastosis and age, all of the aforementioned variables
      remained significantly associated with N+ melanomas in multivariate analyses. No
      associations with self-reported measures of sun exposure, sunburn, or
      pigmentation phenotype were apparent. Our findings provide some support for the
      hypothesis of etiologically separate pathways for melanoma, with N+ melanomas
      appearing less likely to develop in the presence of characteristics suggesting
      high accumulated sun exposure than N- melanomas. However, it is possible that
      high UV exposure causes involution of nevi, thus reducing the density of nevi in
      exposed skin and thereby the probability of N+ melanoma.

PMID- 16103455
TI  - 5,10-methylenetetrahydrofolate reductase 677 and 1298 polymorphisms, folate
      intake, and microsatellite instability in colon cancer.
AB  - The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene plays a critical role
      in folate metabolism. Studies on the association between MTHFR polymorphisms and
      length changes in short tandem repeat DNA sequences [microsatellite instability
      (MSI)] are inconsistent. Using data from colon cancer cases (n=503) enrolled as
      part of an existing population-based case-control study, we investigated the
      association between MTHFR 677 and MTHFR 1298 polymorphisms and MSI. We also
      examined whether the association was modified by folate intake. Participants were
      case subjects enrolled as part of the North Carolina Colon Cancer Study.
      Consenting cases provided information about lifestyle and diet during in-home
      interviews as well as blood specimens and permission to obtain tumor blocks. DNA
      from normal and tumor tissue sections was used to determine microsatellite status
      (MSI). Tumors were classified as MSI if two or more microsatellite markers
      (BAT25, BAT26, D5S346, D2S123, and D17S250) had changes in the number of DNA
      sequence repeats compared with matched nontumor tissue. Tumors with one positive
      marker (MSI-low) or no positive markers (microsatellite stable) were grouped
      together as non-MSI tumors (microsatellite stable). MTHFR 677 and MTHFR 1298
      genotypes were determined by real-time PCR using the 5' exonuclease (Taqman)
      assay. Logistic regression was used to calculate odds ratio (OR) and 95%
      confidence intervals (95% CI). MSI was more common in proximal tumors (OR, 3.8;
      95% CI, 1.7-8.4) and in current smokers (OR, 4.0; 95% CI, 1.6-9.7). Compared with
      MTHFR 677 CC referent, MTHFR 677 CT/TT genotype was inversely associated with MSI
      among White cases (OR, 0.36; 95% CI, 0.16-0.81) but not significant among African
      Americans. Although not statistically significant, a similar inverse association
      was observed between MTHFR 677 CT/TT genotype and MSI among the entire case
      subjects (OR, 0.54; 95% CI, 0.26-1.10). Among those with adequate folate intake
      (>400 microg total folate), we found strong inverse associations between combined
      MTHFR genotypes and MSI (677 CC+1298 AC/CC, OR, 0.09; 95% CI, 0.01-0.59; 677
      CT/TT+1298 AA, OR, 0.13; 95% CI, 0.02-0.85) compared with the combined wild-type
      genotypes (677 CC+1298 AA). This protective effect was not evident among those
      with low folate (<400 microg total folate) intake. Our results suggest that MTHFR
      variant genotypes are associated with reduced risk of MSI tumors under conditions
      of adequate folate intake, although the data are imprecise due to small numbers.
      These results indicate that the relationship between MTHFR genotypes and MSI is
      influenced by folate status.

PMID- 16103456
TI  - Dietary benzo[a]pyrene intake and risk of colorectal adenoma.
AB  - We carried out a clinic-based case-control study specifically designed to address
      the hypothesis that dietary intake of polycyclic aromatic hydrocarbons (PAH) is
      associated with colorectal adenoma risk. We developed a food frequency
      questionnaire with detailed questions on meat-cooking methods and doneness levels
      and a benzo[a]pyrene (BaP) database (as a surrogate for total carcinogenic PAHs)
      based on the collection and analysis of a wide range of food samples. We
      estimated BaP intake derived from meat and from all foods to test its
      relationship with risk of colorectal adenomas. The median (10th and 90th
      percentiles) BaP intake in controls was 5 ng/d (0.2 and 66 ng/d) estimated from
      meat and 73 ng/d (35 and 140 ng/d) from all foods. In cases, median BaP intake
      was 17 ng/d (0.5 and 101 ng/d) from meat and 76 ng/d (44 and 163 ng/d) from all
      foods. Multivariate analysis was carried out on 146 cases and 228 controls. The
      odds ratios (95% confidence interval) for dietary BaP from meat with the first
      quintile as the reference group were 1.19 (0.51-2.80) for the second quintile,
      1.71 (0.76-3.83) for the third quintile, 2.16 (0.96-4.86) for the fourth
      quintile, and 2.82 (1.24-6.43) for the fifth quintile (Ptrend=0.01). Increased
      risk of colorectal adenomas was more strongly associated with BaP intake
      estimated from all foods: 2.61 (1.08-6.29) for the second quintile, 4.21 (1.79
      9.91) for the third quintile, 2.45 (0.98-6.12) for the fourth quintile, and 5.60
      (2.20-14.20) for the fifth quintile (Ptrend=0.002). This study provides evidence
      that dietary BaP plays a role in colorectal adenoma etiology.

PMID- 16103457
TI  - Identifying susceptibility genes for prostate cancer--a family-based association
      study of polymorphisms in CYP17, CYP19, CYP11A1, and LH-beta.
AB  - Polymorphisms in genes that code for enzymes or hormones involved in the
      synthesis and metabolism of androgens are compelling biological candidates for
      prostate cancer. Four such genes, CYP17, CYP19, CYP11A1, and LH-beta, are
      involved in the synthesis and conversion of testosterone to dihydrotestosterone
      and estradiol. In a study of 715 men with and without prostate cancer from 266
      familial and early-onset prostate cancer families, we examined the association
      between prostate cancer susceptibility and common single-nucleotide polymorphisms
      in each of these four candidate genes. Family-based association tests revealed a
      significant association between prostate cancer and a common single-nucleotide
      polymorphism in CYP17 (P=0.004), with preferential transmission of the minor
      allele to unaffected men. Conditional logistic regression analysis of 461
      discordant sibling pairs from these same families reaffirmed the association
      between the presence of the minor allele in CYP17 and prostate cancer risk (odds
      ratio, 0.51; 95% confidence interval, 0.28-0.92). These findings suggest that
      variation in or around CYP17 predicts susceptibility to prostate cancer. Family
      based association tests may be especially valuable in studies of genetic
      variation and prostate cancer risk because this approach minimizes confounding
      due to population substructure, which is of particular concern for prostate
      cancer given the tremendous variation in the worldwide incidence of this disease.

PMID- 16103458
TI  - Positive and negative associations of human leukocyte antigen variants with the
      onset and prognosis of adult glioblastoma multiforme.
AB  - Associations of genetic factors with malignant gliomas have been modest. We
      examined the relationships of human leukocyte antigen (HLA) and related
      polymorphisms to glioblastoma multiforme in adult Caucasians (non-Hispanic
      Whites) from the San Francisco Bay area. For 155 glioblastoma multiforme patients
      and 157 control subjects closely matched by ethnicity, age, and gender, PCR-based
      techniques resolved alleles at HLA-A, -B, -C, and -DRB1 loci along with short
      tandem repeat polymorphisms of MICA exon 5 and TNFb. By multivariable logistic
      regression, B*13 and the B*07-Cw*07 haplotype were positively associated with
      glioblastoma multiforme (P=0.01 and <0.001, respectively), whereas Cw*01 was the
      only variant showing a negative association (P=0.05). Among glioblastoma
      multiforme patients, progression to death after diagnosis was slower in those
      with A*32 (relative hazard, 0.45; P<0.01) and faster in those with B*55 (relative
      hazard, 2.27; P<0.01). Thus, both the occurrence and the prognosis of
      glioblastoma multiforme could be associated with specific but different HLA
      genotypes. B*07 and the B*07-Cw*07 haplotype are much more common in Caucasians
      than other ethnic groups in the U.S., which may partially explain the higher
      incidence of glioblastoma multiforme in Caucasians.

PMID- 16103459
TI  - Height, age at menarche, and risk of epithelial ovarian cancer.
AB  - OBJECTIVE: We hypothesized that the hormonal changes of adolescence influence
      ovarian cancer risk particularly in younger women. We investigated this
      possibility by examining the relationship between ovarian cancer and adult height
      and age at menarche as both factors reflect pubertal hormonal levels. METHODS:
      Participants were a population-based sample of women with incident ovarian cancer
      (n=794) and control women randomly selected from the Australian Electoral Roll
      (n=855). The women provided comprehensive reproductive and lifestyle data during
      a standard interview. RESULTS: Although neither height nor age at menarche was
      significantly related to the risk of ovarian cancer overall, increasing height
      was associated with increasing risk of the subgroup of mucinous borderline
      ovarian cancer (odds ratio, 5.3; 95% confidence interval, 1.5-19.1 for
      women>or=175 cm compared with women <160 cm, Ptrend=0.02). Similarly, later age
      at menarche was associated with increasing risk of mucinous borderline cancers
      (odds ratio, 3.8; 95% confidence interval, 1.3-11.4 for those with age at
      menarche>or=14 years compared with those <12 years, Ptrend=0.003). Women with
      mucinous borderline cancers were significantly younger than the women diagnosed
      with invasive cancers (mean 44 versus 57 years; P<0.0001). CONCLUSIONS:
      Development of mucinous borderline ovarian cancers, predominantly diagnosed in
      women ages under 50 years, seems to be associated with age at menarche and
      attained adult height. These results are consistent with our original hypothesis
      that pubertal levels of reproductive hormones and insulin-like growth factor-I
      influence ovarian cancer risk in younger women.

PMID- 16103460
TI  - Cyclooxygenase-2 expression in FAP patients carrying germ line MYH mutations.
AB  - Familial adenomatous polyposis (FAP) is an autosomal condition caused by
      inherited mutations in the adenomatous polyposis coli (APC) or in the MYH genes.
      Clinical trials have established that nonsteroidal anti-inflammatory drugs
      (NSAID) are effective in preventing the development as well as reducing the size
      and decreasing the number of adenomas in FAP patients. Our aim was to evaluate
      the cyclooxygenase-2 (COX-2) expression in surgical specimens from patients with
      no evidence of germ line APC mutations but carrying germ line MYH mutations. COX
      2 expression was evaluated through immunohistochemical and mRNA analysis in
      carcinomas, adenomas, and healthy mucosa from six patients carrying germ line
      biallelic MYH mutations. A modulation of COX-2 expression from adenoma (lower
      level) to carcinoma (higher level) was observed in all patients by both
      immunohistochemical and mRNA analysis. Moreover, patients with MYH mutations
      showed a weak COX-2 expression in the whole colorectal mucosa, as for classic FAP
      patients carrying germ line APC mutations. All together, our data suggest that
      biallelic MYH patients might benefit from NSAID treatment, because in these
      patients COX-2 is overexpressed in the whole colorectal mucosa, a finding
      possibly related to the interplay between COX-2 and APC protein being the APC
      gene a common target of mutations in MYH patients.

PMID- 16103461
TI  - Absence of TP53 codon 249 mutations in young Guinean children with high aflatoxin
      exposure.
AB  - Infection with hepatitis viruses and chronic exposure to high levels of dietary
      aflatoxins are the major etiologic agents for hepatocellular carcinoma in west
      Africa. A challenge for the prevention of hepatocellular carcinoma in this region
      is that both hepatitis B virus and aflatoxin exposures start early in life;
      indeed, aflatoxin exposures can start in utero and continue unabated throughout
      childhood. A mutation in the TP53 tumor suppressor gene at codon 249 (TP53 Ser249
      mutation) has been reported previously for hepatocellular carcinoma tumors and
      matched plasma DNA samples in individuals from areas with high aflatoxin
      exposure. We examined whether the TP53 Ser249 mutation could be observed in DNA
      found in plasma of young children (ages 2-5 years) from Guinea, west Africa, a
      region of high aflatoxin exposure. Plasma aflatoxin-albumin adducts were present
      in 119 of 124 (96%) of the children, geometric mean of positives 9.9 pg/mg
      albumin (95% confidence interval, 8.8-11.0 pg/mg). This is the level and
      prevalence of exposure observed previously in adults. Following PCR amplification
      of plasma-derived DNA and detection using mass spectrometry, none of the samples
      were found to contain the TP53 Ser249 mutation. Because approximately 50% of the
      hepatocellular carcinomas in adults in west Africa have this specific TP53 Ser249
      mutation, a lack of detection in samples from children ages <5 years may indicate
      that a window of opportunity for intervention exists that could be exploited to
      lower hepatocellular carcinoma risk.

PMID- 16103462
TI  - Dietary folate, alcohol consumption, and risk of ovarian cancer in an Italian
      case-control study.

PMID- 16103463
TI  - No association between fatty acid intake and adenomatous polyp recurrence in the
      polyp prevention trial.

PMID- 16103464
TI  - Summaries for patients. Benefits and harms of warfarin plus aspirin after acute
      coronary events.

PMID- 16103465
TI  - Summaries for patients. The outcomes and costs of diabetes prevention with a diet
      and exercise program or metformin: a computer model.

PMID- 16103466
TI  - Summaries for patients. Estimating outcome in patients with HIV-related lymphoma.

PMID- 16103467
TI  - Summaries for patients. Association of quality of care with survival of elderly
      managed care patients.

PMID- 16103468
TI  - Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome:
      meta-analysis with estimates of risk and benefit.
AB  - BACKGROUND: After the acute coronary syndrome, adding warfarin to standard
      aspirin therapy decreases myocardial infarction and stroke but increases major
      bleeding. PURPOSE: To quantify the risks and benefits of warfarin therapy after
      the acute coronary syndrome. DATA SOURCES: MEDLINE from 1990 to October 2004.
      Additional data were obtained from study authors. Clinical risk factors were used
      to classify hypothetical patients into cardiovascular and bleeding risk groups on
      the basis of published data. STUDY SELECTION: Randomized trials comparing
      intensive warfarin therapy (international normalized ratio > 2.0) plus aspirin
      with aspirin alone after the acute coronary syndrome. DATA EXTRACTION: Two
      reviewers independently selected studies and extracted data on study design;
      quality; and clinical outcomes, including myocardial infarction, stroke,
      revascularization, death, and major and minor bleeding. Rate ratios for outcomes
      were calculated and pooled by using the method of DerSimonian and Laird. DATA
      SYNTHESIS: Ten trials involving a total of 5938 patients (11,334 patient-years)
      met the study criteria. Compared with aspirin alone, warfarin plus aspirin was
      associated with a decrease in the annual rate of myocardial infarction (0.022 vs.
      0.041; rate ratio, 0.56 [95% CI, 0.46 to 0.69]), ischemic stroke (0.004 vs.
      0.008; rate ratio, 0.46 [CI, 0.27 to 0.77]), and revascularization (0.115 vs.
      0.135; rate ratio, 0.80 [CI, 0.67 to 0.95]). Warfarin was associated with an
      increase in major bleeding (0.015 vs. 0.006; rate ratio, 2.5 [CI, 1.7 to 3.7]).
      Mortality did not differ. LIMITATIONS: Two large studies provided most of the
      data. Studies did not include coronary stenting, and results should not be
      applied to patients with stents. Relative risk reductions may not be consistent
      across risk groups. CONCLUSIONS: For patients with the acute coronary syndrome
      who are at low or intermediate risk for bleeding, the cardiovascular benefits of
      warfarin outweigh the bleeding risks.

PMID- 16103469
TI  - Clinical outcomes and cost-effectiveness of strategies for managing people at
      high risk for diabetes.
AB  - BACKGROUND: Lifestyle modification can forestall diabetes in high-risk people,
      but the long-term cost-effectiveness is uncertain. OBJECTIVE: To estimate the
      effects of the lifestyle modification program used in the Diabetes Prevention
      Program (DPP) on health and economic outcomes. DESIGN: Cost-effectiveness
      analysis using the Archimedes model. DATA SOURCES: Published basic and
      epidemiologic studies, clinical trials, and Kaiser Permanente administrative
      data. TARGET POPULATION: Adults at high risk for diabetes (body mass index >24
      kg/m2, fasting plasma glucose level of 5.2725 to 6.9375 mmol/L [95 to 125 mg/dL],
      2-hour glucose tolerance test result of 7.77 to 11.0445 mmol/L [140 to 199
      mg/dL]). TIME HORIZON: 5 to 30 years. PERSPECTIVE: Patient, health plan, and
      societal. INTERVENTIONS: No prevention, DPP's lifestyle modification program,
      lifestyle modification begun after a person develops diabetes, and metformin.
      MEASUREMENTS: Diagnosis and complications of diabetes. RESULTS OF BASE-CASE
      ANALYSIS: Compared with no prevention program, the DPP lifestyle program would
      reduce a high-risk person's 30-year chances of getting diabetes from about 72% to
      61%, the chances of a serious complication from about 38% to 30%, and the chances
      of dying of a complication of diabetes from about 13.5% to 11.2%. Metformin would
      deliver about one third the long-term health benefits achievable by immediate
      lifestyle modification. Compared with not implementing any prevention program,
      the expected 30-year cost/quality-adjusted life-year (QALY) of the DPP lifestyle
      intervention from the health plan's perspective would be about 143,000 dollars.
      From a societal perspective, the cost/QALY of the lifestyle intervention compared
      with doing nothing would be about 62,600 dollars. Either using metformin or
      delaying the lifestyle intervention until after a person develops diabetes would
      be more cost-effective, costing about 35,400 dollars or 24,500 dollars per QALY
      gained, respectively, compared with no program. Compared with delaying the
      lifestyle program until after diabetes is diagnosed, the marginal cost
      effectiveness of beginning the DPP lifestyle program immediately would be about
      201,800 dollars. RESULTS OF SENSITIVITY ANALYSIS: Variability and uncertainty
      deriving from the structure of the model were tested by comparing the model's
      results with the results of real clinical trials of diabetes and its
      complications. The most critical element of uncertainty is the effectiveness of
      the lifestyle program, as expressed by the 95% CI of the DPP study. The most
      important potentially controllable factor is the cost of the lifestyle program.
      Compared with no program, lifestyle modification for high-risk people can be made
      cost-saving over 30 years if the annual cost of the intervention can be reduced
      to about 100 dollars. LIMITATIONS: Results depend on the accuracy of the model.
      CONCLUSIONS: Lifestyle modification is likely to have important effects on the
      morbidity and mortality of diabetes and should be recommended to all high-risk
      people. The program used in the DPP study may be too expensive for health plans
      or a national program to implement. Less expensive methods are needed to achieve
      the degree of weight loss seen in the DPP.

PMID- 16103470
TI  - A prognostic index for systemic AIDS-related non-Hodgkin lymphoma treated in the
      era of highly active antiretroviral therapy.
AB  - BACKGROUND: The established International Prognostic Index for lymphomas has not
      included patients with systemic AIDS-related non-Hodgkin lymphoma. OBJECTIVE: To
      establish the most appropriate prognostic index for use in patients with systemic
      AIDS-related non-Hodgkin lymphoma. DESIGN: A prospective study involving
      univariate and multivariable analyses of patients with AIDS-related non-Hodgkin
      lymphoma whose data were used to examine standard and new criteria for survival
      after diagnosis. SETTING: The Chelsea and Westminster cohort of HIV-1-infected
      persons. PATIENTS: 9621 HIV-positive patients, 111 in whom AIDS-related non
      Hodgkin lymphoma was treated after 1996, in the era of highly active
      antiretroviral therapy (HAART). INTERVENTION: Cox proportional hazards regression
      analysis to determine the prognostic significance of multiple clinicopathologic
      variables. RESULTS: Survival of patients with AIDS-related non-Hodgkin lymphoma
      has increased in the HAART era (log-rank chi-square, 9.23; P = 0.002). Univariate
      analyses using the established International Prognostic Index factors of age,
      tumor stage, lactate dehydrogenase level, Eastern Cooperative Oncology Group
      performance status, and number of extranodal sites were confirmed to be
      significant variables. Regression modeling for patients in whom disease was
      diagnosed after 1996 revealed only 2 independent predictors of death:
      International Prognostic Index risk group and CD4 cell count. These predictors
      yielded 4 internally validated risk strata with predicted 1-year survival rates
      of 82%, 47%, 20%, and 15% (P < 0.001). Prognostic risk scores in the highest
      quartile yielded a likelihood ratio for death of 7.90 (hazard ratio, 1.0),
      whereas a prognostic score less than 1.0 yielded a likelihood ratio of 0.23
      (hazard ratio, 0.15 [95% CI, 0.06 to 0.33]). LIMITATIONS: The sample was small,
      and different HAART regimens were used. CONCLUSIONS: For patients with AIDS
      related non-Hodgkin lymphoma that was diagnosed in the era of HAART, application
      of the International Prognostic Index remains useful. The addition of CD4 cell
      count provides further independent prognostic information. Patients who present
      with AIDS-related non-Hodgkin lymphoma and a low CD4 cell count have a poor
      prognosis; this information can be used to guide therapeutic options.

PMID- 16103471
TI  - Quality of care is associated with survival in vulnerable older patients.
AB  - BACKGROUND: Although assessment of the quality of medical care often relies on
      measures of process of care, the linkage between performance of these process
      measures during usual clinical care and subsequent patient outcomes is unclear.
      OBJECTIVE: To examine the link between the quality of care that patients received
      and their survival. DESIGN: Observational cohort study. SETTING: Two managed care
      organizations. PATIENTS: Community-dwelling high-risk patients 65 years of age or
      older who were continuously enrolled in the managed care organizations from 1
      July 1998 to 31 July 1999. MEASUREMENTS: Quality of care received by patients (as
      measured by a set of quality indicators covering 22 clinical conditions) and
      their survival over the following 3 years. RESULTS: The 372 vulnerable older
      patients were eligible for a mean of 21 quality indicators (range, 8 to 54) and
      received, on average, 53% of the care processes prescribed in quality indicators
      (range, 27% to 88%). Eighty-six (23%) persons died during the 3-year follow-up.
      There was a graded positive relationship between quality score and 3-year
      survival. After adjustment for sex, health status, and health service use,
      quality score was not associated with mortality for the first 500 days, but a
      higher quality score was associated with lower mortality after 500 days (hazard
      ratio, 0.64 [95% CI, 0.49 to 0.84] for a 10% higher quality score). LIMITATIONS:
      The observational design limits causal inference regarding the effect of quality
      of care on survival. CONCLUSIONS: Better performance on process quality measures
      is strongly associated with better survival among community-dwelling vulnerable
      older adults.

PMID- 16103472
TI  - Evaluation and management of the patient with pulmonary arterial hypertension.
AB  - Increased pressure in the pulmonary circulation, or pulmonary hypertension, is a
      common disorder that may complicate various cardiopulmonary conditions, including
      severe obstructive airways disease and left ventricular dysfunction. An increase
      in pulmonary arterial pressure that is not due to coexistent cardiopulmonary
      disease, known as pulmonary arterial hypertension, may occur in the absence of a
      demonstrable cause (idiopathic or familial); as a complication of systemic
      conditions, such as connective tissue disease, HIV infection, or chronic liver
      disease; or as a result of the use of fenfluramine anorexigens, amphetamines, or
      cocaine. The development of disease-specific therapies for pulmonary arterial
      hypertension over the past decade underscores the importance of diagnosing
      pulmonary hypertension early in the course of the condition and implementing a
      treatment strategy that is based on the condition's cause and severity. In this
      review, the authors present approaches to the diagnosis and management of
      pulmonary arterial hypertension, using a hypothetical case to highlight the key
      management points.

PMID- 16103473
TI  - Promoting informed choice: transforming health care to dispense knowledge for
      decision making.
AB  - Ours is an era in which patients seek greater engagement in health care choices,
      increasing the demand for high-quality information about clinical options.
      Providing support for informed choice is not straightforward, however, because of
      challenges faced by clinicians, health systems, and consumers. Greater use of
      written or electronic tools can help to clarify choices for patients, but
      decision aids cannot replace the human element in facilitating informed choice.
      The ideal solution is to couple information with high-quality decision counseling
      to help patients understand the potential risks, benefits, and uncertainties of
      clinical options and to assist them in selecting the option that best
      accommodates their personal preferences. Decision counseling can be offered by 3
      types of providers: clinicians who lack formal informed-choice training ("usual
      care"), clinicians with formal informed-choice training, or trained third parties
      who function as impartial decision counselors. Controlled studies are needed to
      determine which model is best, but none appears to be ideal. The health care
      system cannot truly support informed decision making without correcting the
      underlying obstacles that impede patient access to needed information. New
      information technology solutions, training programs, and reimbursement schemes
      are necessary. Patient demand for guidance will only increase as clinical options
      multiply and the world of information continues its rapid growth. Today's health
      care system is unprepared for the convergence of these 2 burgeoning domains, and
      the need to address systemic deficiencies will grow more urgent over time.

PMID- 16103474
TI  - Trying to predict the future for people with diabetes: a tough but important
      task.

PMID- 16103475
TI  - Modeling complex medical decision problems with the Archimedes model.

PMID- 16103476
TI  - Improving patient care can set your brain on fire.

PMID- 16103477
TI  - Lessons from a patient.

PMID- 16103478
TI  - Screening for abdominal aortic aneurysms.

PMID- 16103479
TI  - Target blood pressure and kidney disease.

PMID- 16103480
TI  - Target blood pressure and kidney disease.

PMID- 16103481
TI  - High-output heart failure associated with anagrelide therapy for essential
      thrombocytosis.

PMID- 16103482
TI  - Subungual splinter hemorrhages: a clinical window to inhibition of vascular
      endothelial growth factor receptors?

PMID- 16103483
TI  - Disseminated aspergillosis mimicking hepatic veno-occlusive disease.

PMID- 16103484
TI  - Genomics and economics.

PMID- 16103485
TI  - Climate change and health.

PMID- 16103486
TI  - Climate change and health.

PMID- 16103487
TI  - Climate change and health.

PMID- 16103488
TI  - Rehabilitation and acute stroke care.

PMID- 16103490
TI  - Choice of antihypertensives after acute ischemic stroke.

PMID- 16103492
TI  - Are children with type 1 diabetes immunocompromised?

PMID- 16103495
TI  - Effect of thiazolidinediones on lipid profile.

PMID- 16103497
TI  - Benzene rings.

PMID- 16103498
TI  - Patient demand and politics push Herceptin forward.

PMID- 16103500
TI  - Critical time for health care says new CMA President.

PMID- 16103501
TI  - Countries continue to ratify land mines treaty.

PMID- 16103502
TI  - Health Canada lukewarm on Vioxx panel findings.

PMID- 16103503
TI  - New ethical requirements at the NIH: implications for CIHR and Canada.

PMID- 16103504
TI  - Analgesia through endogenous cannabinoids.

PMID- 16103505
TI  - A 67-year-old woman with recurrent hypoglycemia: non-islet cell tumour
      hypoglycemia.

PMID- 16103506
TI  - Stroke prevention.

PMID- 16103507
TI  - Does lumbar surgery for chronic low-back pain make a difference?

PMID- 16103508
TI  - A 42-year-old man with a rapidly growing lesion of the soft palate.

PMID- 16103509
TI  - Assessing the risk of waiting for coronary artery bypass graft surgery among
      patients with stenosis of the left main coronary artery.
AB  - BACKGROUND: Significant controversy remains over how urgently coronary artery
      bypass graft surgery (CABG) should be scheduled, particularly for patients with
      stenosis of the left main coronary artery. Our main objective was to evaluate the
      safety of waiting for CABG among patients with left main coronary artery disease
      using a standardized triage system. METHODS: We identified 561 consecutive
      patients with stenosis of the left main coronary artery who were scheduled to
      undergo CABG between Apr. 1, 1999, and Mar. 31, 2003. Using standardized triage
      criteria, patients were assigned to 1 of 4 waiting queues: "emergent," "in
      hospital urgent," "out-of-hospital semi-urgent A" and "out-of-hospital semi
      urgent B." Postoperative outcome measures were in-hospital death from any cause
      and a composite outcome measure of in-hospital death from any cause, a prolonged
      requirement for postoperative mechanical ventilation (> 24 h) and a prolonged
      postoperative hospital stay (> 9 d). Waiting-time variables included the specific
      queue, whether patients waited longer than the standard time established for each
      queue and whether patients were upgraded to a more urgent queue. Logistic
      regression analysis was used to identify independent predictors of the composite
      outcome; propensity scores (probability of being assigned to a specific queue)
      were entered into the model to adjust for patient variability among queues.
      RESULTS: Of the 561 patients, 65 (11.6%) were assigned to the emergent group, 343
      (61.1%) to the in-hospital urgent group, 91 (16.2%) to the semi-urgent A queue
      and 62 (11.1%) to the semi-urgent B queue. Four patients (0.7%) died while
      waiting for surgery. The median waiting times were as follows: emergent group, 0
      days; in-hospital urgent group, 2 days; 30 days in the semi-urgent A group and 49
      days in the semi-urgent B group. A total of 52 patients (9.3%) were upgraded to a
      more urgent queue, and 147 patients (26.2%) waited longer than the standard times
      for their respective queue. The overall in-hospital mortality was 5.5% (n = 31),
      and the composite outcome was 32.6% (n = 183). Independent predictors of the
      composite outcome were myocardial infarction within 7 days before surgery,
      preoperative renal failure, ejection fraction of less than 40%, age greater than
      70 years and stenosis of left main coronary artery greater than 70%. Waiting-time
      variables were associated with neither a significantly higher mortality nor
      morbidity outcome. INTERPRETATION: For selected patients with stenosis of the
      left main coronary artery, waiting for CABG did not appear to be associated with
      increased mortality or morbidity.

PMID- 16103510
TI  - Childhood predictors of smoking in adolescence: a follow-up study of Montreal
      schoolchildren.
AB  - BACKGROUND: The factors that cause children to become smokers in adolescence
      remain unclear. Although parental smoking and peer pressure may play a role,
      physiological factors such as lung volume have also been identified. METHODS: To
      investigate these and other possible childhood predictors of teenage smoking, we
      gathered follow-up data on 191 Montreal schoolchildren, aged 5-12 years (average
      9.2 yr) when first examined. At an average age of 13.0 years, they answered
      further questions on their health and smoking behaviour and provided a second set
      of spirometric measurements. RESULTS: At the second survey, 80% of the children
      had entered high school and 44% had become smokers. Reaching puberty between the
      surveys was the most significant determinant of becoming a smoker: 56.4% of the
      124 children postpubertal at the second survey had taken up smoking, versus 17.9%
      of the 67 who were still prepubertal (p = 0.001). We found salivary cotinine
      level, a measure of uptake of environmental tobacco smoke, to be an independent
      predictor of becoming a teenage smoker; even after adjustment for sex,
      socioeconomic status of parents, a crowding index, and the numbers at home of
      siblings, adult smokers and cigarettes smoked, it remained significant for both
      groups: postpubertal (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.2-3.0)
      and prepubertal (OR 2.1, 95% CI 1.0- 4.5). The influence of forced vital capacity
      was marginally significant only in the postpubertal group (OR 5.0, 95% CI 0.88
      28.3). INTERPRETATION: The proportion of nicotine absorbed from that available in
      environmental tobacco smoke during childhood is associated with subsequent
      smoking in adolescence. The more efficient absorption of nicotine seen in some
      children may be related to physiological factors such as lung capacity.

PMID- 16103511
TI  - Should patients with stenosis of the left main coronary artery waiting for bypass
      grafting be given priority?

PMID- 16103512
TI  - A new childhood pathway for transmission of an increased likelihood of smoking?

PMID- 16103513
TI  - Tips for learners of evidence-based medicine: 5. The effect of spectrum of
      disease on the performance of diagnostic tests.

PMID- 16103514
TI  - Sex and gender: what is the difference?

PMID- 16103515
TI  - Intraoperative protein sparing with glucose.
AB  - We examined the hypothesis that glucose infusion inhibits amino acid oxidation
      during colorectal surgery. We randomly allocated 14 patients to receive
      intravenous glucose at 2 mg x kg(-1) x min(-1) (glucose group) starting with the
      surgical incision or an equivalent amount of normal saline 0.9% (control group).
      The primary endpoint was whole body leucine oxidation; secondary endpoints were
      leucine rate of appearance and nonoxidative leucine disposal as determined by a
      stable isotope tracer technique (L-[1-(13)C]leucine). Circulating concentrations
      of glucose, lactate, insulin, glucagon, and cortisol were measured before and
      after 2 h of surgery. Leucine rate of appearance, an estimate of protein
      breakdown, and nonoxidative leucine disposal, an estimate of protein synthesis,
      decreased in both groups during surgery (P < 0.05). Leucine oxidation
      intraoperatively decreased from 13 +/- 3 to 4 +/- 3 micromol x kg(-1) x h(-1) in
      the glucose group (P < 0.05 vs. control group) whereas it remained unchanged in
      the control group. Hyperglycemia during surgery was more pronounced in patients
      receiving glucose (9.7 +/- 0.5 mmol/l, P < 0.05 vs. control group) than in
      patients receiving normal saline (7.1 +/- 1.0 mmol/l). The administration of
      glucose caused an increase in the circulating concentration of insulin (P < 0.05)
      resulting in a lower glucagon/insulin quotient than in the control group (P <
      0.05). Intraoperative plasma cortisol concentrations increased in both groups (P
      < 0.05), whereas plasma concentrations of lactate and glucagon did not change.
      The provision of small amounts of glucose was associated with a decrease in amino
      acid oxidation during colorectal surgery.

PMID- 16103516
TI  - Reticulocyte changes after experimental anemia and erythropoietin treatment of
      horses.
AB  - Availability of recombinant human erythropoietin (EPO) has facilitated use to
      enhance red blood cell production, and therefore aerobic performance, in human
      and equine athletes. Recombinant human EPO promotes growth and differentiation of
      equine erythroid precursor cells, but in some horses repeat administration
      induces immune interference with endogenous EPO resulting in fatal anemia.
      Although blood reticulocyte parameters acquire unique changes in humans treated
      with EPO, with manual enumeration methods, horses were not considered to release
      reticulocytes from the bone marrow into circulation, even under severe
      erythropoietic stress. The goals of this study were to determine whether
      reticulocytes could be detected and characterized in horses that are anemic or
      have been treated with EPO using a modern hematology analyzer. Anemia was induced
      in six horses by removal of 30 ml of blood/kg of body wt over 24 h. After 28
      days, the horses were treated twice with 55 U/kg of EPO (Eprex), and after 65
      days they were treated thrice with 73 U/kg of EPO. Blood samples were analyzed
      with the ADVIA120 instrument every 3-5 days and bone marrow samples 7 days after
      anemia and EPO treatments. Analysis of blood reticulocyte parameters by ANOVA in
      a randomized complete block design determined that anemia and EPO induced
      significant (P < or = 0.05) increases in red cell distribution width and
      reticulocyte mean cell volume. Parameters changed only after EPO treatment were
      cellular hemoglobin concentration mean, mean cell volume, reticulocyte
      concentration, proportion of macrocytic reticulocytes, and reticulocyte cellular
      hemoglobin. These findings indicate that horses under erythropoietic stress and
      after EPO treatment release reticulocytes with unique characteristics into
      circulation.

PMID- 16103517
TI  - Modulation of the contractile responses of guinea pig isolated tracheal rings
      after chronic intermittent hypobaric hypoxia with and without cold exposure.
AB  - Previous studies have documented that repetitive exposure to intermittent
      hypoxia, such as that encountered in preparation to high-altitude ascent,
      influences breathing. However, the impact of intermittent hypoxia on airway
      smooth muscle has not been explored. Ascents to high altitude, in addition to
      hypoxia, expose individuals to cold air. The objective of the present study is to
      examine the effect of chronic intermittent hypobaric hypoxia (CIH) and CIH
      combined with cold exposure (CIHC) on tracheal smooth muscle responses to various
      contractile and relaxant agonists. Experiments were performed on tracheal rings
      harvested from adult guinea pigs exposed either to CIH or CIHC [14 days (6 h/day)
      at barometric pressure of 350 mmHg with and without cold exposure of 5 degrees C]
      or to room air (normoxia). CIH and CIHC attenuated maximum contractile responses
      to ACh compared with normoxia. The maximum contractile response to histamine
      decreased with CIH, whereas CIHC restored the response back to normoxia. Both CIH
      and CIHC attenuated maximum contractile responses to 5-HT. Altered contractile
      responses after CIH and CIHC were independent of epithelium. Isoproterenol
      induced relaxation was not altered by CIH, whereas it was enhanced after CIHC,
      and these responses were independent of the epithelium. The data demonstrate that
      intermittent exposure to hypoxia profoundly influences contractile response of
      tracheal smooth muscle, and cold exposure can further modulate the response,
      implying the importance of cold at high altitude.

PMID- 16103518
TI  - Superior laryngeal and hypoglossal afferents tonically influence upper airway
      motor excitability in anesthetized rats.
AB  - Upper airway (UA) muscle activity is stimulated by changes in UA transmural
      pressure and by asphyxia. These responses are reduced by muscle relaxation. We
      hypothesized that this is due to a change in afferent feedback in the ansa
      hypoglossi and/or superior laryngeal nerve (SLN). We examined 1) the
      glossopharyngeal motor responses to UA transmural pressure and asphyxia and 2)
      how these responses were changed by muscle relaxation in animals where one or
      both of these afferent pathways had been sectioned bilaterally. Experiments were
      performed in 24 anesthetized, thoracotomized, artificially ventilated rats.
      Baseline glossopharyngeal activity and its response to UA transmural pressure and
      asphyxia were moderately reduced after bilateral section of the ansa hypoglossi
      (P < 0.05). Conversely, bilateral SLN section increased baseline glossopharyngeal
      activity, augmented the response to asphyxia, and abolished the response to UA
      transmural pressure. Muscle relaxation reduced resting glossopharyngeal activity
      and the response to asphyxia (P < 0.001). This occurred whether or not the ansa
      hypoglossi, the SLN, or both afferent pathways had been interrupted. We conclude
      that ansa hypoglossi afferents tonically excite and SLN afferents tonically
      inhibit UA motor activity. Muscle relaxation depressed UA motor activity after
      section of the ansa hypoglossi and SLN. This suggests that some or all of the
      response to muscle relaxation is mediated by alterations in the activity of
      afferent fibers other than those in the ansa hypoglossi or SLN.

PMID- 16103519
TI  - Influence of fibrillin-1 genotype on the aortic stiffness in men.
AB  - Aortic stiffness is a predictor of cardiovascular mortality. The mechanical
      properties of the arterial wall depend on the connective tissue framework, with
      variation in fibrillin-1 and collagen I genes being associated with aortic
      stiffness and/or pulse pressure elevation. The aim of this study was to
      investigate whether variation in fibrillin-1 genotype was associated with aortic
      stiffness in men. The mechanical properties of the abdominal aorta of 79 healthy
      men (range 28-81 yr) were investigated by ultrasonographic phase-locked echo
      tracking. Fibrillin-1 genotype, characterized by the variable tandem repeat in
      intron 28, and collagen type I alpha 1 genotype characterized by the 2,064 G>T
      polymorphism, were determined by using DNA from peripheral blood cells. Three
      common fibrillin-1 genotypes, 2-2, 2-3, and 2-4, were observed in 50 (64%), 10
      (13%), and 11 (14%) of the men, respectively. Those of 2-3 genotype had higher
      pressure strain elastic modulus and aortic stiffness compared with men of 2-2 or
      2-4 genotype (P = 0.005). Pulse pressure also was increased in the 2-3 genotype
      (P = 0.04). There was no significant association between type 1 collagen genotype
      and aortic stiffness in this cohort. In conclusion, the fibrillin-1 2-3 genotype
      in men was associated with increased aortic stiffness and pulse pressure,
      indicative of an increased risk for cardiovascular disease.

PMID- 16103520
TI  - Diaphragmatic free radical generation increases in an animal model of heart
      failure.
AB  - Heart failure evokes diaphragm weakness, but the mechanism(s) by which this
      occurs are not known. We postulated that heart failure increases diaphragm free
      radical generation and that free radicals trigger diaphragm dysfunction in this
      condition. The purpose of the present study was to test this hypothesis.
      Experiments were performed using halothane-anesthetized sham-operated control
      rats and rats in which myocardial infarction was induced by ligation of the left
      anterior descending coronary artery. Animals were killed 6 wk after surgery, the
      diaphragms were removed, and the following were assessed: 1) mitochondrial
      hydrogen peroxide (H2O2) generation, 2) free radical generation in resting and
      contracting intact diaphragm using a fluorescent-indicator technique, 3) 8
      isoprostane and protein carbonyls (indexes of free radical-induced lipid and
      protein oxidation), and 4) the diaphragm force-frequency relationship. In
      additional experiments, a group of coronary ligation animals were treated with
      polyethylene glycol-superoxide dismutase (PEG-SOD, 2,000 units x kg(-1) x day(
      1)) for 4 wk. We found that coronary ligation evoked an increase in free radical
      formation by the intact diaphragm, increased diaphragm mitochondrial H2O2
      generation, increased diaphragm protein carbonyl levels, and increased diaphragm
      8-isoprostane levels compared with controls (P < 0.001 for the first 3
      comparisons, P < 0.05 for 8-isoprostane levels). Force generated in response to
      20-Hz stimulation was reduced by coronary ligation (P < 0.05); PEG-SOD
      administration restored force to control levels (P < 0.03). These findings
      indicate that cardiac dysfunction due to coronary ligation increases diaphragm
      free radical generation and that free radicals evoke reductions in diaphragm
      force generation.

PMID- 16103521
TI  - Downregulation of diaphragm electron transport chain and glycolytic enzyme gene
      expression in sepsis.
AB  - Cellular energy metabolism is altered in sepsis as a consequence of dysfunction
      of mitochondrial electron transport and glycolytic pathways. The purpose of the
      present study was to determine whether sepsis is associated with compensatory
      increases in gene expression of electron transport chain and glycolytic pathway
      proteins or, alternatively, whether gene expression decreases in sepsis,
      contributing to abnormalities in energy metabolism. Studies were performed using
      diaphragms from control and endotoxin-treated (8 mg x kg(-1) x day(-1)) rats; at
      48 h after endotoxin administration, animals were killed. Microarrays and RNAse
      protection assays were used to assess the expression of several electron
      transport chain components (cytochrome-c oxidase subunits Cox 5A, Cox 5B, and Cox
      6A, ATP synthase, and ATP synthase subunit 5B) and of the rate-limiting enzyme
      for glycolysis, phosphofructokinase (PFK). Western blotting was used to assess
      protein levels for these electron transport chain subunits and PFK. Activity
      assays were used to assess electron transport chain and phosphofructokinase
      function. We found that sepsis evoked 1) a downregulation of genes encoding all
      examined electron transport chain components (e.g., cytochrome-c oxidase 5A
      decreased 45 + 7%, P < 0.01) and PFK (P < 0.001), 2) reductions in protein levels
      for these electron transport chain subunits and PFK (P < 0.05 for each), and 3)
      decreases in mitochondrial state 3 respiration rates and phosphofructokinase
      enzyme activity (P < 0.01 for each comparison). We speculate that these sepsis
      induced reductions in the expression of genes encoding critical electron
      transport and glycolytic proteins contribute to the development and persistence
      of sepsis-induced abnormalities in cellular energy metabolism.

PMID- 16103522
TI  - Epidemiological evidence for the role of physical activity in reducing risk of
      type 2 diabetes and cardiovascular disease.
AB  - Epidemiological studies suggest that physically active individuals have a 30-50%
      lower risk of developing type 2 diabetes than do sedentary persons and that
      physical activity confers a similar risk reduction for coronary heart disease.
      Risk reductions are observed with as little as 30 min of moderate-intensity
      activity per day. Protective mechanisms of physical activity include the
      regulation of body weight; the reduction of insulin resistance, hypertension,
      atherogenic dyslipidemia, and inflammation; and the enhancement of insulin
      sensitivity, glycemic control, and fibrinolytic and endothelial function. Public
      health initiatives promoting moderate increases in physical activity may offer
      the best balance between efficacy and feasibility to improve metabolic and
      cardiovascular health in largely sedentary populations.

PMID- 16103523
TI  - Physical activity and diabetes prevention.
AB  - Diabetes has reached epidemic proportions worldwide and is associated with a
      large economic burden, increased risk of cardiovascular disease, and premature
      mortality. Hyperglycemia is the hallmark clinical manifestation of diabetes and
      evolves through a multifactorial etiology of genetic, environmental, and
      behavioral enablers. Approximately 90% of diabetes cases are the non-insulin
      dependent phenotype, which is characterized by a progressive deterioration in
      insulin-mediated glucose disposal, particularly by peripheral tissues. Our
      hypothesis is that the most proximal behavioral cause of insulin resistance is
      physical inactivity. Indeed, several streams of scientific research have
      demonstrated a role for physical activity in the etiology and prevention of
      diabetes and its related morbidity. In this review we will discuss some of the
      key observational and experimental studies that have examined associations among
      physical activity, cardiorespiratory fitness, and non-insulin-dependent diabetes.

PMID- 16103524
TI  - Point: Flow-mediated dilation does reflect nitric oxide-mediated endothelial
      function.

PMID- 16103525
TI  - Counterpoint: Flow-mediated dilation does not reflect nitric oxide-mediated
      endothelial function.

PMID- 16103529
TI  - Images in cardiology: Intramyocardial dissection after subacute anterior wall
      myocardial infarction.

PMID- 16103530
TI  - Images in cardiology: Mitral valve anterior leaflet prolapse by real time three
      dimensional transthoracic echocardiography.

PMID- 16103531
TI  - The declining prevalence of ST elevation myocardial infarction in patients
      presenting with acute coronary syndromes.
AB  - The management of patients with acute coronary syndromes may be about to undergo
      a dramatic change.

PMID- 16103532
TI  - Heat shock proteins in cardiovascular disease and the prognostic value of heat
      shock protein related measurements.
AB  - Are heat shock protein antibodies directly involved in the pathogenesis of
      cardiovascular disease?

PMID- 16103534
TI  - Improving evidence based cardiac care and policy implementation over the patient
      journey: the potential of coronary heart disease registers.
AB  - Coronary heart disease registers offer considerable potential for providing
      increased support for practitioners, facilitating improvements in patient care,
      and allowing efficient monitoring of care provision and outcomes.

PMID- 16103535
TI  - Images in cardiology: A case of anomalous origin of the right coronary artery
      from the pulmonary artery complicated by acute myocardial infarction.

PMID- 16103536
TI  - Preventing recurrent rheumatic fever: the role of register based programmes.
AB  - Despite dramatic gains of the last century, acute rheumatic fever and rheumatic
      heart disease remain major preventable causes of morbidity and mortality in many
      parts of the world.

PMID- 16103537
TI  - Images in cardiology: Rare case of pericarditis constrictiva.

PMID- 16103538
TI  - Images in cardiology: Precordial ST segment elevation suggestive of anterior
      infarction caused by right coronary artery occlusion.

PMID- 16103539
TI  - Clopidogrel in non-ST segment elevation acute coronary syndromes: an overview of
      the submission by the British Cardiac Society and the Royal College of Physicians
      of London to the National Institute for Clinical Excellence, and beyond.
AB  - A comprehensive appraisal was undertaken on behalf of the British Cardiac Society
      and the Royal College of Physicians of London to assess the use of clopidogrel in
      acute coronary syndromes. The appraisal was submitted to the National Institute
      for Clinical Excellence (NICE) in August 2003 and contributed to the development
      of the recently published guidelines for the use of clopidogrel in acute coronary
      syndromes. The submission to NICE and more recent publications evaluating the use
      of clopidogrel are reviewed.

PMID- 16103540
TI  - Images in cardiology: Inappropriate pacemaker therapy in congestive heart
      failure.

PMID- 16103541
TI  - Cardiovascular risk factors and clinical presentation in acute coronary
      syndromes.
AB  - OBJECTIVE: To investigate the hypothesis that risk factors may be differently
      related to severity of acute coronary syndromes (ACS), with ST elevation used as
      a marker of severe ACS. DESIGN: Cross sectional study of patients with ACS.
      SETTING: 103 hospitals in 25 countries in Europe and the Mediterranean basin.
      PATIENTS: 10,253 patients with a discharge diagnosis of ACS in the Euro heart
      survey of ACS. MAIN OUTCOME MEASURES: Presenting with ST elevation ACS. RESULTS:
      Patients with ACS who were smokers had an increased risk to present with ST
      elevation (age adjusted odds ratio (OR) 1.84, 95% confidence interval (CI) 1.67
      to 2.02). Hypertension (OR 0.65, 95% CI 0.60 to 0.70) and high body mass index
      (BMI) (p for trend 0.0005) were associated with less ST elevation ACS. Diabetes
      mellitus was also associated with less ST elevation, but only among men. Prior
      disease (infarction, chronic angina, revascularisation) and treatment with
      aspirin, beta blockers, or statins before admission were also associated with
      less ST elevation. After adjustment for age, sex, prior disease, and prior
      medication, smoking was still significantly associated with increased risk of ST
      elevation (OR 1.53, 95% CI 1.38 to 1.69), whereas hypertension was associated
      with reduced risk (OR 0.75, 95% CI 0.69 to 0.82). Obesity (BMI > 30 kg/m2 versus
      < 25 kg/m2) was independently associated with less risk of presenting with ST
      elevation among women, but not among men. CONCLUSION: Among patients with ACS,
      presenting with ST elevation is strongly associated with smoking, whereas
      hypertension and high BMI (in women) are associated with less ST elevation,
      independently of prior disease and medication.

PMID- 16103542
TI  - Images in cardiology: An unusual case of right ventricular dilatation.

PMID- 16103543
TI  - Increased titres of anti-human heat shock protein 60 predict an adverse one year
      prognosis in patients with acute cardiac chest pain.
AB  - OBJECTIVE: To assess whether antibodies to human heat shock protein 60 (anti
      huhsp60) or to mycobacterial heat shock protein 65 (anti-mhsp65) predict an
      adverse one year prognosis in patients admitted with acute cardiac chest pain.
      DESIGN: Prospective observational study. SETTING: Teaching hospital. PATIENTS:
      588 consecutive emergency admissions of patients with acute chest pain of
      suspected cardiac origin. MAIN OUTCOME MEASURES: Anti-huhsp60 and anti-mhsp65
      titres were assayed on samples drawn on the morning after admission. The end
      points after discharge were coronary heart disease death, non-fatal myocardial
      infarction, coronary artery bypass grafting, percutaneous transluminal coronary
      angioplasty, angiogram, or readmission with further cardiac ischaemic chest pain.
      RESULTS: During follow up after discharge (mean of 304 days, range 1-788 days),
      277 patients had at least one of the study outcomes. Patients with increased
      titres of anti-huhsp60 had an adverse prognosis (hazard ratio 1.56 (95%
      confidence interval 1.09 to 2.23) comparing highest versus lowest quartiles, p =
      0.015). Anti-mhsp65 titres were not predictive. CONCLUSIONS: Patients admitted
      with acute cardiac chest pain and increased titres of anti-huhsp60 had an adverse
      one year prognosis.

PMID- 16103544
TI  - Images in cardiology: Fibrin thrombus causing myocardial infarction in a patient
      with patent coronary arteries.

PMID- 16103545
TI  - Calcific retinal embolism as an indicator of severe unrecognised cardiovascular
      disease.
AB  - OBJECTIVE: To describe the association between calcific retinal embolism (CRE)
      and cardiac valve stenosis. DESIGN AND SETTING: Retrospective chart review of
      patients with clinical criteria for CRE. PATIENTS: 24 patients with CRE who
      underwent two dimensional echocardiography between 1976 and 1998. RESULTS: Nine
      patients (38%) had calcific valve stenosis, which was haemodynamically severe in
      five patients (four aortic and one mitral), four of whom had no cardiac symptoms.
      Six patients underwent surgical intervention (aortic valve replacement in three
      patients, mitral and aortic valve replacement in one patient, removal of calcific
      cardiac pseudotumour in one patient, and carotid endarterectomy in one patient).
      CONCLUSIONS: CRE may be the presenting feature of otherwise asymptomatic,
      clinically important underlying cardiovascular disease and, in particular,
      haemodynamically severe calcific valve stenosis.

PMID- 16103546
TI  - Images in cardiology: Left sided unilateral pulmonary oedema.

PMID- 16103547
TI  - Cardiac magnetic resonance imaging: long term reproducibility of the late
      enhancement signal in patients with chronic coronary artery disease.
AB  - OBJECTIVE: To determine long term reproducibility of the late enhancement (LE)
      signal in contrast enhanced magnetic resonance imaging (MRI) and potential
      changes of the signal after revascularisation. METHODS: 33 patients (29 men, mean
      (SD) 61 (11) years) with coronary artery disease (CAD) and left ventricular
      dysfunction (ejection fraction 30 (7)%) underwent two contrast enhanced MRI
      procedures within 9 (3) months. Fifteen patients (group A: 14 men, 59 (12) years)
      had no interventions between the two studies. Eighteen patients underwent
      revascularisation after MRI 1 (group B: 15 men, 62 (9) years). Changes in the LE
      signal between the first and second MRIs were investigated in both groups as well
      as intraobserver and interobserver variabilities for delineation of the signal.
      RESULTS: The LE signal was highly reproducible in groups A and B for segmental
      analysis (concordance 86% v 82%, respectively; kappa = 0.70 v 0.67) and summed
      scores (group A: r = 0.97, p < 0.001; group B: r = 0.93, p < 0.001). The LE
      signal was quantified as 27 (27) cm3 in group A versus 30 (16) cm3 in group B in
      the first MRI and 26 (25) cm3 versus 30 (15) cm3, respectively, for the second
      MRI (both not significant). Moreover, low intraobserver and interobserver
      variabilities were observed in segmental analysis (kappa = 0.86 and 0.74,
      respectively, for group A, and kappa = 0.87 and 0.82, respectively, for group B).
      CONCLUSION: In patients with chronic CAD, the LE signal in contrast enhanced MRI
      is very stable over an extended time period. These results further characterise
      contrast enhanced MRI as a useful tool for myocardial viability assessment. Low
      intraobserver and interobserver variabilities promise robustness of the method
      for clinical application.

PMID- 16103548
TI  - Headache response to glyceryl trinitrate in patients with and without obstructive
      coronary artery disease.
AB  - OBJECTIVES: To examine the hypothesis that glyceryl trinitrate (GTN) may cause
      headache in patients with normal coronary arteries more often than in patients
      with obstructive coronary artery disease (CAD). This simple assessment may aid
      clinicians in the initial evaluation of chest pain syndrome and possible CAD.
      PATIENTS AND METHODS: 118 patients (66 men and 52 women) with new onset of chest
      pain were enrolled in this study. Patients were excluded from the study if they
      had a history of chronic headache, long term nitrates use, or any coronary artery
      procedures. Mean age of the patients was 62.5 years. Coronary angiography was
      performed within one month of GTN administration with the usual clinical
      indications such as recurrent chest pain, abnormal ECG, or abnormal results of
      stress tests. Thirty patients had normal coronary arteries or minimal or non
      obstructive CAD. Eighty eight patients had obstructive CAD defined as luminal
      narrowing greater than 50% in any one or more of the left or right coronary
      arteries or their major branches. All the patients had a varying degree of relief
      of chest pain with GTN administration within 10 minutes. 36% of patients reported
      significant headache after GTN administration. RESULTS: In patients with normal
      coronary arteries or minimal CAD, 73% had significant headache caused by
      sublingual GTN. In patients with obstructive CAD, only 23% had significant
      headache after GTN use (p < 0.001). There were no differences in patients' sex
      and vascular risk factors concerning the frequency of headache in patients with
      or without obstructive CAD. CONCLUSIONS: GTN causes significantly more frequent
      headache episodes in patients with normal coronary arteries or minimal CAD than
      in patients with obstructive CAD. This unique finding may provide clinicians with
      an additional tool for the differential diagnosis of patients with chest pain
      syndrome.

PMID- 16103549
TI  - Predictors of adverse outcome in patients with arrhythmogenic right ventricular
      dysplasia/cardiomyopathy: long term experience of a tertiary care centre.
AB  - OBJECTIVE: To investigate the predictors for adverse clinical outcome in patients
      with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) during
      long term follow up. METHODS: 61 patients with ARVD/C were studied to assess the
      impact of family history, clinical findings, surface ECG parameters,
      echocardiographic findings, and electrophysiological findings on clinical
      outcome. The prevalence of these risk factors were compared in two patient
      groups: group A (patients with adverse clinical outcome: sudden cardiac death,
      death from heart failure, or heart transplant) and group B (survivors excluding
      patients who received a heart transplant). RESULTS: Mean age at first diagnosis
      was 44 (14) years. The mean follow up duration was 55 (47) months. Ten patients
      (16%) died during follow up. The cause of death of eight of these patients was
      probably arrhythmic. Two patients died of advanced heart failure. Five patients
      underwent heart transplantation because of terminal heart failure. Risk factors
      significantly associated with adverse outcome were history of congestive heart
      failure (p < 0.001), the presence of left ventricular involvement on
      echocardiography (p < 0.001), left atrial dilatation (p < 0.05), prolonged PR
      duration (p < 0.01), prolonged QRS in V1 (p < 0.05), and bundle branch block (p <
      0.05). In multivariate analysis, history of congestive heart failure and presence
      of left ventricular involvement were identified as independent risk predictors
      for an adverse outcome. CONCLUSIONS: Congestive heart failure and left
      ventricular involvement are independently associated with adverse outcome in
      patients with ARVD/C during long term follow up.

PMID- 16103550
TI  - Images in cardiology: Heterotopic heart transplantation: three dimensional image.

PMID- 16103551
TI  - Clopidogrel reduces migraine with aura after transcatheter closure of persistent
      foramen ovale and atrial septal defects.
AB  - OBJECTIVE: To report the clinical events leading to alteration of an
      anticoagulation regimen for patients undergoing transcatheter closure of an
      atrial shunt and how this affected migraine symptoms after the closure procedure.
      METHOD: Audit of a change of anticoagulant regimen. RESULTS: In the first few
      weeks after a closure procedure migraine frequency and severity increased despite
      treatment with aspirin for six months in 71 patients. Severe attacks of migraine
      with aura, including status migrainosus, in the first few weeks after
      transcatheter closure were terminated by addition of clopidogrel to aspirin
      treatment. Therefore, the anticoagulant regimen was changed with addition of
      clopidogrel for the first month after the closure procedure (90 procedures in 89
      patients). Fewer patients had migraine with aura in the first month after
      transcatheter closure when taking the combination of clopidogrel and aspirin
      compared with aspirin alone (11 of 90 (12.2%) v 30 of 71 (42.3%), p < 0.001).
      Episodes of migraine with aura were more severe and more frequent in patients
      taking aspirin alone. CONCLUSION: The combination of clopidogrel for four weeks
      and aspirin for six months is superior to aspirin alone for six months for
      preventing migraine with aura after transcatheter closure of an atrial shunt.
      This beneficial effect of a powerful inhibitor of platelet aggregation suggests
      that platelets may have a role in pathogenesis of migraine. This may be because
      of an effect on serotonin stores. Whether clopidogrel has a role in treatment of
      migraine in other clinical situations requires investigation.

PMID- 16103552
TI  - Images in cardiology: Multiple thrombi in the left atrium.

PMID- 16103553
TI  - Images in cardiology: Diabetic keto-acidosis and hyperkalaemia induced pseudo
      myocardial infarction.

PMID- 16103554
TI  - Prognostic role of cardiac troponin I after percutaneous coronary intervention in
      stable coronary disease.
AB  - OBJECTIVE: To assess the role of cardiac troponin I (cTnI) in predicting outcome
      after percutaneous coronary intervention (PCI). METHODS AND RESULTS: cTnI was
      measured immediately before and at 6, 14, and 24 hours after PCI in 316
      consecutive patients with stable symptoms and native coronary artery disease. The
      study end point was the occurrence of major adverse cardiac events (MACE) at 30
      days and at 18 months after PCI: death, Q wave myocardial infarction (MI), or
      repeat revascularisation in hospital. Postprocedural cTnI increased in 31% of
      patients. The cumulative MACE rate at 18 months was 25% (17.7% due to repeat PCI
      procedures). There was a significant association between postprocedural cTnI
      increase and death, Q wave MI, or both (odds ratio (OR) 3.28, 95% confidence
      interval (CI) 1.7 to 6.4, p = 0.01). Post-PCI cTnI increase had a positive
      predictive value (PPV) for adverse events at 18 months of 0.47 and a negative
      predictive value (NPV) of 0.96 (OR 18.9, 95% CI 9.7 to 37, p < 0.0001). The
      presence of both a postprocedural cTnI rise and a procedural angiographic
      complication gave a PPV for adverse events of 0.69 and an NPV of 0.92 (OR 22.6,
      95% CI 2.6 to 68.6, p = 0.0005). CONCLUSIONS: cTnI increased post-procedurally in
      one third of this stable patient population undergoing elective PCI and was
      independently and significantly predictive of an increased risk of adverse events
      at 18 months, predominantly in the form of repeat PCI.

PMID- 16103555
TI  - Images in cardiology: Cardiac sarcoidosis with delayed enhanced MRI.

PMID- 16103556
TI  - Detection of coronary microembolisation by Doppler ultrasound during percutaneous
      coronary interventions.
AB  - OBJECTIVE: To validate an intracoronary Doppler ultrasound device for high
      intensity transient signals (HITS) detection and to assess the incidence of HITS
      during percutaneous coronary intervention (PCI). METHODS AND RESULTS: In an in
      vitro model, particle count and number of HITS detected by an intracoronary 0.014
      inch Doppler wire were closely correlated (r = 0.97, p < 0.001). In the clinical
      study, 32 patients (mean (SD) age 61 (11) years; 23 men, nine women) with
      coronary artery disease were treated with balloon dilatation and stent
      implantation for a single vessel stenosis. In these patients HITS were detected
      during PCI in 84% (27 of 32). Reproducibility (r = 0.99, p < 0.001) and
      interobserver agreement (r = 0.84, p < 0.001) of HITS counts were significant.
      The number of HITS after stent implantation was significantly higher than after
      balloon dilatation (11 (7) v 2 (4), p < 0.001). Postprocedural coronary flow
      velocity reserve (CFVR) was < 2.0 in 55% (16 of 29) of all patients after balloon
      dilatation and < 2.0 in 23% (six of 26) after stent implantation. The number of
      HITS after stent implantation did not differ significantly between patients with
      CFVR < 2.0 and patients with CFVR > or = 2.0 (12 (8) v 10 (7), not significant).
      CONCLUSIONS: Embolic particles can be detected as HITS by an intracoronary
      Doppler ultrasound device. Coronary microembolism is often observed during PCI,
      especially after stent implantation. However, the incidence of HITS alone does
      not explain a reduced CFVR after PCI.

PMID- 16103557
TI  - Is the severity of congenital heart disease associated with the quality of life
      and perceived health of adult patients?
AB  - OBJECTIVE: To explore whether the severity of congenital heart disease is
      associated with the quality of life and perceived health status of adult
      patients. DESIGN: Descriptive, cross sectional study. SETTING: Adult congenital
      heart disease programme in one tertiary care centre in Belgium. PATIENTS: 629
      patients (378 men, 251 women) with a median age of 24 years. MAIN OUTCOME
      MEASURES: Disease severity was operationalized in terms of initial diagnosis
      (classification of Task Force 1 of the 32nd Bethesda Conference), illness course
      (disease severity index), and current functional status (New York Heart
      Association (NYHA) class, ability index, congenital heart disease functional
      index, and left ventricular ejection fraction). Quality of life was measured by a
      linear analogue scale, the satisfaction with life scale, and the schedule for
      evaluation of individual quality of life. Perceived health status was also
      assessed with a linear analogue scale. RESULTS: Scores derived from the disease
      severity classification systems were weakly negatively associated with quality of
      life and health status, ranging from -0.05 to -0.27. The NYHA functional class
      and ability index were consistently associated with quality of life and perceived
      health. CONCLUSIONS: This study showed that the severity of congenital heart
      disease is marginally associated with patients' quality of life and perceived
      health. Functional status was more related to patients' assessment of their
      quality of life than was the initial diagnosis or illness course.

PMID- 16103558
TI  - Idiopathic restrictive cardiomyopathy in children.
AB  - OBJECTIVE: To define the natural history of idiopathic restrictive cardiomyopathy
      in a paediatric population and to identify any factors predictive of outcome.
      DESIGN: Retrospective analysis of patients born between 1970 and 2002 were
      identified from the Children's Hospital of Pittsburgh cardiology database.
      Demographic data, mode of presentation, echocardiographic and haemodynamic
      findings at diagnosis, survival time, and manner of death were evaluated.
      SETTING: Tertiary referral and transplant centre for paediatric patients with
      cardiac disease. PATIENTS: All local and referred patients with idiopathic
      restrictive cardiomyopathy born after 1970 and under 21 years of age at time of
      diagnosis. RESULTS: 21 patients were identified. Probability of survival at 1, 5,
      and 10 years was 80.5% (95% confidence interval (CI) 58 to 100), 39% (95% CI 17
      to 61), and 20% (95% CI 0 to 42), respectively. Median age of presentation was
      3.8 years (mean (SD) 5.7 (6.1) years). Median survival without transplantation
      was 2.2 years (mean (SD) 4.6 (5.4) years). Age at presentation, sex, and presence
      or absence of heart failure symptoms at presentation were not associated with
      clinical course. Right (p = 0.05) and left ventricular end diastolic pressures (p
      = 0.04) and ratio of left atrial to aortic root dimensions (LA:Ao) (p = 0.03) at
      presentation had a significantly negative correlation with survival time after
      diagnosis. CONCLUSIONS: Without transplantation, most children with restrictive
      cardiomyopathy have a very poor prognosis. Longer survival from diagnosis was
      correlated with lower LA:Ao and cardiac filling pressures at diagnosis. Survival
      time was not influenced by the symptoms present at diagnosis.

PMID- 16103559
TI  - Images in cardiology: Chest pain in a puerperal woman.

PMID- 16103560
TI  - The effect of pacemaker mode on cognitive function.

PMID- 16103561
TI  - Influence of conduction time intervals on symptoms and exercise tolerance in
      patients with heart failure with left ventricular systolic dysfunction.

PMID- 16103562
TI  - Images in cardiology: Transient pericardial effusion after cardiac surgery: often
      unrecognised.

PMID- 16103563
TI  - Secondary prevention with folic acid: results of the Goes extension study.

PMID- 16103564
TI  - Images in cardiology: Cholesterol embolisation syndrome.

PMID- 16103565
TI  - The value of haemostatic markers in the triage of patients with chest pain
      presenting with a normal or non-diagnostic ECG.

PMID- 16103566
TI  - Haplotype analysis of the endothelial nitric oxide synthase gene in relation to
      acute myocardial infarction.

PMID- 16103567
TI  - Prolonged exercise should be considered alongside typical symptoms of acute
      myocardial infarction when evaluating increases in cardiac troponin T.

PMID- 16103569
TI  - Efficiency of a minicourse in radiation reducing techniques: a pilot initiative
      to encourage less irradiating cardiological interventional techniques (ELICIT).

PMID- 16103571
TI  - Angiotensin II, but not aldosterone and renin, correlates positively with
      increased concentrations of N-terminal pro-brain natriuretic peptide in patients
      with chronic heart failure.

PMID- 16103572
TI  - Oral anticoagulation in patients aged 75 years or older with chronic non-valvar
      atrial fibrillation: effectiveness and safety in daily clinical practice.

PMID- 16103573
TI  - Images in cardiology: Coronary angiography in a patient with pulmonary alveolar
      microlithiasis.

PMID- 16103574
TI  - Diagnostic specificity and prognostic value of cardiac troponins in asymptomatic
      chronic haemodialysis patients: a three year prospective study.

PMID- 16103575
TI  - Follow up and optimisation of cardiac pacing.

PMID- 16103576
TI  - Patients' beliefs about their cardiovascular disease.

PMID- 16103577
TI  - Congenital anomalies of the coronary arteries.

PMID- 16103578
TI  - Images in cardiology: Multiple ventricular thrombus in HIV cardiomyopathy.

PMID- 16103579
TI  - Observations on "seroepidemiology study of Leishmania infantum infection in
      Castilla-Leon, Spain".

PMID- 16103580
TI  - Is anthelmintic resistance a threat to the program to eliminate lymphatic
      filariasis?

PMID- 16103581
TI  - Detection of benzimidazole resistance-associated mutations in the filarial
      nematode Wuchereria bancrofti and evidence for selection by albendazole and
      ivermectin combination treatment.
AB  - The Global Program to Eliminate Lymphatic Filariasis has been implemented to
      reduce human microfilaremia to levels low enough to break the transmission of the
      disease by using single annual doses of albendazole in combination with
      diethylcarbamazine or ivermectin. Many veterinary helminth parasites have
      developed resistance against both albendazole and ivermectin. Resistance to
      albendazole in veterinary nematodes is known to be caused by either of two single
      amino acid substitutions from phenylalanine to tyrosine in parasite beta-tubulin
      at position 167 or 200. We have developed assays capable of detecting these
      single nucleotide polymorphisms (SNPs) in Wuchereria bancrofti, and have applied
      them to microfilaria obtained from patients in Ghana and Burkina Faso. One of the
      SNPs was found in worms from untreated populations in both locations. Worms from
      treated patients had significantly higher frequencies of these mutations. These
      findings indicate that a beta-tubulin allele associated with benzimidazole
      resistance is being selected in these populations.

PMID- 16103582
TI  - Drug-resistant malaria in Bangui, Central African Republic: an in vitro
      assessment.
AB  - We used an in vitro isotopic drug sensitivity assay to assess the sensitivity of
      Plasmodium falciparum isolates collected in Bangui, Central African Republic
      between March and July 2004. We tested antimalarials that are currently in use in
      this country (chloroquine, amodiaquine, quinine, and pyrimethamine),
      antimalarials that will become available in this region in the future
      (artemisinin and halofantrine), and prophylactic antimalarials (mefloquine,
      doxycycline, and atovaquone). The proportions of resistant isolates were 37% for
      chloroquine, 15.9% for amodiaquine, 0% for quinine, 0% for dihydroartemisinin,
      1.6% for mefloquine, 3.8% for halofantrine, 4.0% for atovaquone, and 38.3% for
      pyrimethamine. No multi-resistant isolates (showing resistance to more than three
      drugs) were found. A positive correlation was found between the 50% inhibitory
      concentrations values for the following drugs: chloroquine and amodiaquine;
      quinine and halofantrine; chloroquine and dihydroartemisinin; chloroquine and
      halofantrine; amodiaquine and dihydroartemisinin; dihydroartemisinin and
      mefloquine; chloroquine and quinine; and quinine and dihydroartemisinin. These
      findings suggest that the Ministry of Health should recommend a interim policy
      with the amodiaquine plus sulfadoxine-pyrimethamine combination as the first-line
      antimalarial drug in Bangui until better alternative treatments such as
      artemisinin-based combination therapies become available at low prices in the
      Central African Republic.

PMID- 16103583
TI  - Comparison of IgG reactivities to Plasmodium vivax merozoite invasion antigens in
      a Brazilian Amazon population.
AB  - Naturally acquired antibody reactivity to two major Plasmodium vivax vaccine
      candidates was investigated in 294 donors from three malaria-endemic communities
      of Rondonia state, Brazil. Antibody recognition of recombinantly expressed
      antigens covering five different regions of P. vivax reticulocyte binding protein
      1 (PvRBP1) and region II of P. vivax Duffy binding protein (PvDBP-RII) were
      compared. Positive IgG responses to these antigens were significantly related to
      the level of malaria exposure in terms of past infections and years of residence
      in the endemic area when corrected for age. The highest prevalence of anti-PvRBP1
      total IgG antibodies corresponded to the amino acid regions denoted PvRBP1(431
      748) (41%) and PvRBP1(733-1407) (47%). Approximately one-fifth of positively
      responding sera had titers of at least 1:1,600. Total IgG responses to PvDBP-RII
      were more prevalent (67%), of greater magnitude, and acquired more rapidly than
      those to individual PvRBP1 antigens. Responses to both PvRBP1 and PvDBP-RII were
      biased toward the cytophilic subclasses IgG1 and IgG3. These data provide the
      first insights on acquired antibody responses to PvRBP1 and a comparative view
      with PvDBP-RII that may prove valuable for understanding protective immune
      responses to these two vaccine candidates as they are evaluated as components of
      multitarget blood-stage vaccines.

PMID- 16103584
TI  - Distinguishing recrudescences from new infections in antimalarial clinical
      trials: major impact of interpretation of genotyping results on estimates of drug
      efficacy.
AB  - The use of molecular genotyping to distinguish recrudescence from new infections
      has become common in antimalarial clinical trials. However, methods used to
      interpret genotyping results have not been standardized. We analyzed data from
      3,000 patients enrolled in clinical trials at seven sites in Uganda. Late
      treatment failure requiring genotyping occurred in 51% of the patients. Among
      samples successfully genotyped, 21% were definitive new infections (no
      recrudescent strains present on day of failure), 35% were definitive
      recrudescences (only recrudescent strains present), and 44% were mixed (new and
      recrudescent strains present). The probability of having a mixed genotyping
      result increased as transmission intensity increased. At the highest transmission
      site, the estimated risk of treatment failure increased from 34% to 84% for
      chloroquine plus sulfadoxine-pyrimethamine, from 18% to 45% for amodiaquine plus
      sulfadoxine-pyrimethamine, and from 12% to 57% for amodiaquine plus artesunate,
      depending on whether mixed genotyping results were classified as new infections
      or recrudescences, respectively. The method used to classify treatment outcomes
      can have a major impact on estimates of drug efficacy, especially in areas of
      high transmission intensity.

PMID- 16103585
TI  - Effectiveness of quinine monotherapy for the treatment of Plasmodium falciparum
      infection in pregnant women in Lambarene, Gabon.
AB  - Pregnant women participating in a longitudinal immuno-epidemiologic survey in
      Lambarene, Gabon, and presenting with Plasmodium falciparum parasitemia at
      monthly blood smear examinations were offered treatment with oral 7-day quinine
      monotherapy according to national health guidelines. A total of 50 pregnant women
      were offered 7-day oral quinine sulfate 10 mg/kg thrice daily. Clinical
      examinations and laboratory tests were performed on Days 28 and 56 to assess the
      effectiveness of this standard regimen. By Day 28, the effectiveness of the 7-day
      quinine regimen was 60% (95% confidence interval: 46-72%). We conclude that a 7
      day course of quinine has a poor effectiveness and that alternative treatment
      regimens for malaria in pregnant women should be assessed.

PMID- 16103586
TI  - Short report: no evidence of cardiotoxicity of atovaquone-proguanil alone or in
      combination with artesunate.
AB  - Combinations are set to become the mainstay in treatment and prophylaxis of
      malaria due to Plasmodium falciparum. Various antimalarials have been implicated
      in cardiotoxicity via prolongation of the QTc interval. Atovaquone-proguanil is
      an effective and increasingly popular antimalarial choice when used alone or with
      artesunate in areas of drug resistance. We report the results of an investigation
      carried out on the Thai-Burmese border in 42 patients randomized to receive
      either atovaquone-proguanil or atovaquone-proguanil-artesunate for three days.
      Electrocardiographic recordings were made at baseline and one hour after each
      dose. There was no statistically significant change in QTc interval between
      baseline and any subsequent readings in either treatment group or the cohort as a
      whole. We conclude that atovaquone-proguanil shows no evidence of cardiotoxicity
      either alone or when combined with artesunate.

PMID- 16103587
TI  - Detection of leishmanial antigen in the urine of patients with visceral
      leishmaniasis by a latex agglutination test.
AB  - Diagnosis of visceral leishmaniasis (VL) is usually done by demonstration of
      parasites in tissue smears. However, obtaining these smears may be risky,
      painful, and difficult. Antibody-based diagnostics are limited by their inability
      to predict active disease. In this study, a new latex agglutination test (KAtex),
      which detects parasite antigen in freshly voided and boiled urine, was evaluated
      in patients with VL before the start (n = 382) and at the end of treatment (n =
      273); 185 healthy controls from leishmaniasis-endemic region were also studied.
      The KAtex result was positive in 87% (95% confidence interval [CI] = 83.3-90.3).
      However, at the end of treatment only 3% (95% CI = 1.6-6.2) patients were
      positive. The specificity of the test was 99% and 2 of 185 healthy controls
      tested positive. Positive and negative predictive values were 0.994 and 0.788,
      respectively. KAtex is a promising test, and in a simplified and improved format
      it could be applied meaningfully in the diagnosis of VL.

PMID- 16103588
TI  - The sensitivity of clinical isolates of Leishmania from Peru and Nepal to
      miltefosine.
AB  - Clinical isolates of Leishmania, from visceral leishmaniasis (VL) cases in Nepal
      and from cutaneous leishmaniasis (CL) cases in Peru, were cultured using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to
      type species and strain. Promastigotes from 38 isolates, within eight passages
      from isolation, were used to infect mouse peritoneal macrophage cultures in
      vitro, and the amastigote sensitivity to miltefosine was determined. The
      concentration required to kill 50% of intracellular amastigotes from Nepalese VL
      isolates, all typed as Leishmania (L.) donovani (N = 24) from both Sbv responders
      and nonresponders, ranged from 8.7 to 0.04 microg/mL. In contrast, the
      concentration required to kill 50% intracellular amastigotes from isolates from
      Peru, typed as L.(V.) braziliensis (N = 8), was > 30 to 8.4 microg/mL, L.(V.)
      guyanensis (N = 2) > 30 to 1.9 microg/mL, L.(L.) mexicana (N = 1) > 30 microg/mL,
      and L. (V.) lainsoni (N = 4) was 3.4 to 1.9 microg/mL. This demonstrates a
      notable difference in the intrinsic sensitivity of Leishmania species to
      miltefosine in vitro. If this model can be correlated to therapeutic outcome, it
      may have implications for the interpretation of clinical trials.

PMID- 16103589
TI  - The value of a new microculture method for diagnosis of visceral leishmaniasis by
      using bone marrow and peripheral blood.
AB  - We have demonstrated that the microculture method (MCM) enables the diagnosis of
      visceral leishmaniasis (VL) with samples from both the bone marrow (BM) and
      peripheral blood (PB). The MCM is superior to the traditional culture method
      (TCM) as determined by its higher sensitivity in the detection of promastigotes
      and the more rapid time for emergence of promastigotes. The sensitivity of MCM
      (100% in BMs and 77.8-100% in PB) was considerably higher than that of the TCM
      (37.5-100% in BMs and 0-100% in PB) according to decreasing parasite density (P <
      0.05). The concentration of parasites in buffy coats has increased the
      sensitivity of both methods, especially that of the MCM. Detection of
      promastigotes by MCM requires lower amounts of culture media (25-50 microL) and
      shorter incubation periods (2-7 days) than TCM (2.5-3.5 mL and 15-35 days,
      respectively). MCM was found to be valuable with the advantages of simplicity and
      sensitivity, in addition to being cost-effective in the routine diagnosis for VL
      in Adana Turkey.

PMID- 16103590
TI  - Atypical clinical variants in New World cutaneous leishmaniasis: disseminated,
      erysipeloid, and recidiva cutis due to Leishmania (V.) panamensis.
AB  - In recent times, there has been an increase in the number of reports for new and
      rare variants of cutaneous leishmaniasis (CL). Here, we describe three unusual
      clinical forms of CL identified in Ecuadorian children. A total of 131 patients
      with CL were diagnosed over a 2-year period of active search. In 3 (2.29%), the
      lesions were very unusual; these included erysipeloid, recidiva cutis (LRC), and
      disseminated leishmaniasis (DL). The erysipeloid case is characterized by
      erythematous and indurated plaque seen on the face of a 5-year-old boy; the LRC
      one is differentiated by slowly progressing red-brown papules around large scars
      of healed sores in a 6-year-old girl, and the DL case is characterized by dozens
      of cutaneous ulcers distributed in the whole body of a 1-year-old girl.
      Leishmania parasites were isolated by lesion aspirate and analyzed by the
      technique multilocus enzyme electrophoresis (MLEE). All three isolates were
      identified as Leishmania (Viannia) panamensis. These distinct clinical variants
      rarely have been reported previously in the American cutaneous leishmaniasis, and
      for the first time L. (V.) panamensis was identified as the etiologic agent. Our
      cases extend the spectrum of clinical presentations in New World leishmaniasis.

PMID- 16103591
TI  - Microsporidiosis in travel-associated chronic diarrhea in immune-competent
      patients.
AB  - We analyzed retrospectively 21 immune-competent travelers with chronic traveler's
      diarrhea (3-6 weeks) after returning from recreational travel to the tropics with
      stool samples positive for microsporidia. Nine patients had been treated with
      albendazole and 12 patients had been treated symptomatically. Diarrhea resolved
      in 8 of 9 and 12 of 12 patients, respectively. In the albendazole group,
      Encephalitozoon intestinalis was cleared in 4 of 4 patients and Enterocytozoon
      bieneusi persisted in 7 of 7 patients (2 patients were lost to follow-up). In the
      symptomatic treated group microsporidia persisted in stool samples of all
      patients. We conclude that there is only a transient correlation between
      detection of microsporidia in stool and gastrointestinal symptoms, and suggest
      that microsporidia infection may cause clinical symptoms during the early stages
      of infection that resolve even though the microsporidia may persist.

PMID- 16103592
TI  - Enzyme immunoassay of Cryptosporidium-specific immunoglobulin G antibodies to
      assess longitudinal infection trends in six communities in British Columbia,
      Canada.
AB  - A newly developed enzyme-linked immunosorbent assay (ELISA) that detects
      immunoglobulin G antibodies to the 27-kDa Cryptosporidium parvum sporozoite
      surface antigen was used to test 4,097 sera collected from pregnant women in 6
      communities in British Columbia, Canada, between January 1996, and December 1997.
      Waterborne outbreaks of cryptosporidiosis occurred in two of the study
      communities during the period of follow-up, and ELISA seropositivity was high in
      all six communities during the study period (77% positive to 92% positive). In
      the community with the largest outbreak, levels of antibody to the 27-kDa antigen
      increased rapidly and then decayed to background levels within 3-4 months of the
      peak of the epidemic curve. Trends in serologic reactivity were complex in all
      communities, and increased antibody levels not related temporally to known
      waterborne outbreaks were also observed. Serological assays may provide more
      accurate information regarding community levels of Cryptosporidium infection.

PMID- 16103593
TI  - Infection by human immunodeficiency virus-1 is not a risk factor for amebiasis.
AB  - The purpose of this study was to determine whether HIV-1 infected patients in our
      community were more susceptible to Entamoeba histolytica and Entamoeba dispar
      infection than non-HIV-infected individuals. The prevalence and frequency of
      invasive amebiasis was determined in 203 HIV+/AIDS subjects and 140 close
      relatives or sexual partners, all of whom were HIV-. Anti-E. histolytica
      antibodies (IgG, IgA) were assessed as indicators of E. histolytica invasive
      infection. Polymerase chain reaction (PCR) was used for the characterization of
      the Entamoeba species. The prevalence estimated with PCR data showed that E.
      histolytica infection was more common in the HIV+/AIDS group (25.32%), than in
      HIV- contacts (18.46%). E. histolytica + E. dispar infection was more frequent in
      HIV+/AIDS patients (13.3%), than in HIV- contacts (0.7%). E. histolytica and/or
      E. dispar infection was highly prevalent in HIV+/AIDS patients (34.1%) without
      evidence of recent or current invasive disease. Contacts of HIV+/AIDS patients
      who were infected with E. histolytica were asymptomatic cyst passers. Our results
      suggest that E. histolytica strains prevalent in the studied community appear to
      be of low pathogenic potential.

PMID- 16103594
TI  - Pathologic changes in lungs caused by Mexican isolates of Trypanosoma cruzi in
      the acute phase of infection in mice.
AB  - Chagas' disease, which is caused by the protozoan parasite Trypanosoma cruzi, is
      a significant public health problem in the Americas. Its clinical presentation
      varies significantly in different geographic regions. Using experimental
      infection in mice, we studied the pathologic changes in lungs in the acute phase
      of the disease caused by three Mexican isolates of T. cruzi. Clusters of
      parasites and inflammatory reactions were found in the walls of conducting
      airways and pulmonary vessels. Inflammation was more intense in the small
      vessels. Although the parasites were not found in the alveolar walls, severe
      pathologic changes in these structure were observed and included alveolar wall
      thickening and inflammatory infiltration. Furthermore, serous liquid, fibrin
      fibers, hyaline membranes, and erythrocytes were found in the alveolar spaces.
      The pathomorphologic changes observed in the infected mice are consistent with
      pneumonitis.

PMID- 16103595
TI  - Identifying health centers in honduras infested with Rhodnius prolixus using the
      seroprevalence of Chagas disease in children younger than 13 years.
AB  - The objective of this study is to determine if a Chagas disease protocol starting
      with a serological survey is as reliable at identifying insect-infested areas as
      one using the gold standard entomological survey. The study found that health
      center areas infested with Rhodnius prolixus were identified using a threshold
      seroprevalence of 0.1%. The serological survey took half the time and was 30%
      less expensive than the entomological survey. Developing countries with limited
      resources may find this strategy useful in combating Chagas disease. This
      strategy also identifies seropositive children, which facilitates their
      treatment.

PMID- 16103596
TI  - Application of an alternative Aedes species (Diptera: culicidae) surveillance
      method in Botucatu City, Sao Paulo, Brazil.
AB  - One of the main problems with dengue is the control of Aedes aegypti, its major
      vector. In Brazil, the current control program for Ae. aegypti and Aedes
      albopictus populations includes larval density surveys. An interesting
      alternative is the use of a distinct index, the Premise Condition Index (PCI).
      This tool relates conditions of property, such as houses and yards, and the
      degree of shade with the occurrence of Aedes sp. oviposition, and is calculated
      as scores from 3 to 9. The lowest score indicates property in good condition and
      an unfavorable breeding environment, while the highest score indicates property
      at high risk for infestation by Aedes sp. The present study is based on the
      application of the PCI in an urban area of Botucatu, Brazil to confirm its
      effectiveness.

PMID- 16103597
TI  - The presence of Plasmodium falciparum gametocytes in human blood increases the
      gravidity of Anopheles gambiae mosquitoes.
AB  - We conducted a field study in an area of endemic malaria transmission in western
      Kenya to determine whether mosquitoes that feed on gametocyte-infected blood but
      do not become infected have reduced or enhanced fecundity in comparison to
      mosquitoes fed on uninfected blood. Fifteen paired membrane-feeding experiments
      were conducted in which two strains of Anopheles gambiae mosquitoes were
      simultaneously fed on either Plasmodium falciparum-infected blood from children
      or uninfected control blood from adults. The presence of noninfecting gametocytes
      in blood increased the probability that An. gambiae would produce eggs after one
      blood meal by sixfold (odds ratio for control relative to infected blood group
      0.16; 95% CI 0.10-0.23). This result could not be explained by variation in blood
      meal size or hemoglobin content between hosts. When children cleared their
      infections, the difference in gravidity between mosquitoes fed on their blood and
      uninfected adults disappeared, suggesting this phenomenon is due to the presence
      of Plasmodium gametocytes in blood and not to host-specific factors such as age.
      This result was observed in two mosquito strains that differ in their innate
      fecundity, suggesting it may apply generally. To our knowledge, this is the first
      time that Plasmodium has been implicated as enhancing vector gravidity.

PMID- 16103598
TI  - Molecular taxonomic study of Chagas disease vectors from the phyllosoma,
      lecticularia, and rubrofasciata complexes.
AB  - The Triatiominae (Hemiptera: Reduviidae) are hematophagous hemipters of
      importance because they transmit Trypanosoma cruzi, the causal agent of Chagas
      disease. The aim of this study was to define the possible relationships between
      species of the Phyllosoma complex (Triatoma mazzottii, Triatoma pallidipennis,
      and Triatoma longipennis) and species of other complexes present in Mexico that
      have not been previously analyzed (Triatoma lecticularia and Triatoma rubida). In
      addition, it was determined the inclusion of Triatoma bassolsae in the Phyllosoma
      complex by using 10 isoenzymatic systems (corresponding to the 14 loci). Results
      of isoenzymatic study show that between the species of the Phyllosoma complex
      including Triatoma bassolsae, the polymorphism of the analyzed enzymes ranges
      from 14% to 50% (P < or = 0.95) and the species from external complexes showed
      polymorphism values of 43% (Triatoma lecticularia), 43% (Triatoma rubida), and
      36% (Triatoma infestans). The genetic tree shows a clear difference between
      species of the Phyllosoma complex and the other complexes.

PMID- 16103599
TI  - Differential introgression of chromsomal regions between Anopheles gambiae and
      An. arabiensis.
AB  - Evidence for introgression between Anopheles gambiae and An. arabiensis has
      accumulated for some time. We examined the fate of introgressed DNA directly,
      using microsatellite markers located throughout the genome. Introgressed X
      chromosomes were removed within two generations. Furthermore, substantial
      differences in introgressive capacity between the two autosomes were found. After
      introgression from An. arabiensis into An. gambiae, most introgressed alleles at
      third chromosome markers, particularly those on 3R, decreased steadily,
      indicating selection against them. No such pattern was observed for 2L markers
      and several 2R markers. The frequency of introgressed alleles on 2L were close to
      the original frequency even after 19 generations, whereas only two 2R markers
      showed a modest decrease. Even though limited information was available on the
      reciprocal cross, the pattern appears to be identical. Although the decrease in
      frequency of the introgressed X chromosome can be attributed to the presence of
      sterility and inviability effects, the variation in introgressive capacity of the
      autosomes does not appear to be explained by the presence of inversion
      polymorphisms, or regions causing hybrid sterility and inviability. These results
      can have some important implications for the spread of insecticide resistance and
      the control of these vector populations via the release of transgenic mosquitoes.

PMID- 16103600
TI  - Identification of mammalian blood meals in mosquitoes by a multiplexed polymerase
      chain reaction targeting cytochrome B.
AB  - To date, no polymerase chain reaction diagnostic technique exists to directly
      identify mammalian blood meals from mosquitoes by sized DNA fragments following
      agarose gel electrophoresis. We have developed a vertebrate-specific multiplexed
      primer set based on mitochondrial cytochrome b to identify the mammalian blood
      hosts of field-collected mosquitoes. Although designed for the study of African
      malaria vectors, the application of this tool is not restricted to this disease
      system. Validation of this diagnostic technique on dried anopheline and culicine
      field specimens collected in Zambia and Mali demonstrated that blood meals could
      be identified 2-7 months after collection. Time course experiments showed that
      host DNA was detectable in frozen mosquito abdomens 24-30 hours post-feeding.
      Additionally, multiple blood meals from different mammals could be detected in a
      single mosquito. This diagnostic assay will be a valuable tool for identifying
      the blood meals of field-collected mosquitoes where people and alternative mammal
      hosts are present.

PMID- 16103601
TI  - Behavioral responses to DDT and pyrethroids between Anopheles minimus species A
      and C, malaria vectors in Thailand.
AB  - Behavioral responses of two field populations of Anopheles minimus complex
      species A and C for contact and non-contact actions of chemicals were compared
      during and after exposure to operational field concentrations of DDT (2 g/m2),
      deltamethrin (0.02 g/m2), and lambdacyhalothrin (0.03 g/m2) using an excito
      repellency escape chamber. The two populations were collected from the Mae Sot
      District in Tak Province (species A) and the Tri Yok District in Kanchanaburi
      Province (species C) in western Thailand. Female mosquitoes of both populations
      rapidly escaped from chambers after direct contact with DDT, deltamethrin, and
      lambdacyhalothrin. The non-contact repellency response to DDT and the two
      synthetic pyrethroids was pronounced with An. minimus species A; however, non
      contact repellency was relatively weak with An. minimus species C, but remained
      significantly greater than the paired controls (P < 0.05). We conclude that
      strong contact irritancy was present in both test populations, whereas non
      contact repellency also played a significant role in the escape response of An.
      minimus species A.

PMID- 16103602
TI  - Field evaluation of spatial repellency of metofluthrin impregnated plastic strips
      against mosquitoes in Hai Phong City, Vietnam.
AB  - Spatial repellency of metofluthrin-impregnated polyethylene plastic strips
      against mosquitoes, Aedes aegypti and Culex quinquefasciatus, were studied in a
      residential area in Hai Phong city, Vietnam. Thirty houses were selected as trial
      sites; half of these were assigned as untreated control and the other half were
      assigned for treatment. Primarily, irrespective of the room size, one room was
      treated with one strip. The dominant species in the trial sites were Culex
      quinquefasciatus and Aedes aegypti. A rapid decrease in the mosquito index was
      observed immediately after the treatment with metofluthrin strips, and treatment
      was effective for at least 6 weeks.

PMID- 16103603
TI  - Detection and characterization of Wolbachia infections in Wuchereria bancrofti
      (Spirurida: Onchocercidae) var. pacifica and Aedes (Stegomyia) polynesiensis
      (Diptera: Culicidae).
AB  - Despite control programs based on mass drug administration (MDA) of
      microfilaricidal compounds, Bancroftian lymphatic filariasis remains a problem in
      French Polynesia. For an alternative strategy to MDA, we investigated the
      potential role of Wolbachia to control filarial transmission. Wolbachia are
      intracellular alpha-proteobacteria endosymbionts that infect a broad range of
      insects and nematodes. These bacteria have a suspected role in the pathogenesis
      of filariasis. They also may be useful in mosquito control through cytoplasmic
      incompatibility. To detect and characterize these bacteria in the filarial and
      mosquito-vectors in French Polynesia, a survey was conducted on field-collected
      mosquitoes and microfilariae from infected people. Samples were analyzed by a
      polymerase chain reaction and gene sequencing. The results indicate that these
      bacteria are widespread. Sequence analysis of the wsp and ftsZ genes positioned
      the Aedes polynesiensis Wolbachia in cluster A and Wuchereria bancrofti var.
      pacifica Wolbachia in cluster D. The implications for possible improved treatment
      and vector control are discussed.

PMID- 16103604
TI  - Late benefits 10-18 years after drug therapy for infection with Schistosoma
      haematobium in Kwale District, Coast Province, Kenya.
AB  - Late benefits of remote antischistosomal therapy were estimated among long-term
      residents of an area with high transmission of Schistosoma haematobium
      (Msambweni, Kenya) by comparing infection and disease prevalence in two local
      adult cohorts. We compared 132 formerly treated adults (given treatment in
      childhood or adolescence > or = 10 years previously) compared with 132 age- and
      sex-matched adults from the same villages who had not received prior treatment.
      The prevalence of current infection, hematuria, and ultrasound bladder
      abnormalities were significantly lower among the previously treated group, who
      were found to be free of severe bladder disease. Nevertheless, heavy infection
      was equally prevalent (2-3%) in both study groups, and present rates of
      hydronephrosis were not significantly different. Therapy given in childhood or
      adolescence appears to improve risk for some but not all manifestations of S.
      haematobium infection in later adult life. Future prospective studies of
      continued treatment into adulthood will better define means to obtain optimal,
      community-based control of S. haematobium-related disease in high-risk locations.

PMID- 16103605
TI  - Efficacy of myrrh in the treatment of human Schistosomiasis mansoni.
AB  - Myrrh (Mirazid) has been produced and marketed as an antischistosomal drug since
      2001. The current study was designed to assess the efficacy of a commercially
      available product of myrrh. One hundred four individuals, infected with
      Schistosoma mansoni, were randomized in two groups, one for myrrh and the second
      for praziquantel. Treatment-whether myrrh or praziquantel-was given twice with a
      3-week interval. The cure rate with myrrh was very low, 15.6% after the first
      treatment, and 8.9% after the second treatment. Egg reduction among uncured
      persons was also very low, being 17.2% after the first treatment, and 28% after
      the second treatment. Praziquantel cure rate was 73.7% and 76.3%, and individuals
      still passing S. mansoni ova after praziquantel treatment showed a substantial
      reduction in the geometric mean egg counts (84% and 88.2% after the first and
      second treatments, respectively). When 34 individuals-uncured after two myrrh
      treatments-were offered praziquantel in the standard dose, 32 of them stopped
      passing S. mansoni eggs when tested 4 weeks post-treatment. The results of the
      current study raise serious doubts about the antischistosomal properties of
      Mirazid.

PMID- 16103606
TI  - Primary hydatid cyst of the breast with elevated CA 19-9 level.
AB  - Breast masses secondary to hydatid cyst disease are placed on the differential
      diagnosis of breast tumors under guidance of the literature. In addition to their
      characteristic appearance on mammography, many specific parameters for diagnosis
      are required. In this report, the relation of serum CA 19-9 levels to the primary
      breast cyst hydatid was evaluated in both preoperative and postoperative periods.

PMID- 16103607
TI  - Status of forest onchocerciasis in the Lower Cross River basin, Nigeria:
      entomologic profile after five years of ivermectin intervention.
AB  - In the Lower Cross River basin in Nigeria, no pre-control entomologic profile of
      Onchocerca volvulus infection in the local Simulium damnosum population was
      available prior to the initiation of an ivermectin control program in 1995. A
      longitudinal entomologic study was therefore carried out over a 12-month period
      (January-December 2001) at the Agbokim waterfalls and Afi River, which are
      breeding sites of S. damnosum in the river basin. A total of 9,287 adult S.
      damnosum were caught on human bait; 9,048 (97.43%) were dissected, of which 313
      (3.46%) were infected. Annual biting rates (ABRs) of 42,419 and 28,346 bites per
      persons per year were recorded at the Agbokim Waterfalls and Afi River,
      respectively. The annual transmission potential (ATP) was 419 infective larvae
      per person per year at the Agbokim Waterfalls and 427 at the Afi River. Monthly
      biting rate and monthly transmission potential varied significantly (P < 0.05) at
      the two sites. Transmission was highly seasonal from April to September,
      corresponding to the peak biting period of the vector. The high ATP and ABR
      values are a measure of the mesoendemicity of onchocerciasis in the river basin.
      There was a significant F(0).05 (1, 10) (P < 0.05) variation in the relative fly
      abundance from both sites. It was observed that human activities such as farming,
      fishing, timber cutting, and hunting are done in the early morning and late
      afternoon, which corresponds to the peak diurnal biting period of the vector.
      Changes in these practices and attitudes may markedly affect the disease
      intensity and transmission.

PMID- 16103608
TI  - Acute pancreatitis caused by tapeworm in the biliary tract.
AB  - Taeniasis is a helminthic infection endemic in southeast Asia, including Taiwan.
      Recent studies suggest that Asian Taenia is a new subspecies of Taenia saginata
      and has been renamed as Taenia saginata asiatica. It is usually asymptomatic or
      associated with only mild gastrointestinal symptoms. We report the case of a 52
      year-old woman with acute epigastric pain and vomiting. Her levels of amylase and
      lipase were significantly elevated on admission. Gastrointestinal endoscopy
      showed proglottids of a tapeworm in the papilla of the duodenum. The epigastric
      pain subsided and the amylase and lipase levels decreased after removal of the
      tapeworm by endoscopy and anthelminthic treatment. Although parasites are not an
      uncommon cause of pancreatitis, especially in disease-endemic areas, it is rare
      for Taenia to cause acute pancreatitis.

PMID- 16103609
TI  - Platelet dysfunction-eosinophilia syndrome in parasitized Venezuelan children.
AB  - Platelet dysfunction was detected in six children with purpura and eosinophilia.
      We conducted clinical evaluations, hematologic and platelet function tests,
      clotting studies (bleeding time, prothrombin time, partial thromboplastin time,
      thrombin time, factor XIII, factor VIII, and von Willebrand factor), assays for
      IgG and IgM antibodies to platelets, and a search for stool parasites. Mild
      bleeding phenomena (ecchymoses, petechiae, epistaxis, and gingival) were
      transient. All children showed intestinal parasites and marked eosinophilia (mean
      count = 2,615.2 cells/muL, 95% confidence interval = 1,259.6-5,429.8). Main
      abnormalities included prolonged bleeding times (50%) and defective aggregation
      with collagen (100%) adrenaline (66%), or ADP (66%). Antibodies to platelets were
      not detected. Anti-parasite therapy reversed the hemorrhagic manifestations and
      normalized eosinophil counts and platelet alterations. No relationship could be
      established between excess eosinophils, intensity of bleeding, or type and degree
      of platelet abnormalities. Thrombocytopathic features mimicked the intrinsic
      defect of storage pool disease. The possible pathogenic roles of eosinophilia and
      parasitism are reviewed. This is the first report of this pathologic combination
      in Latin American children.

PMID- 16103610
TI  - Risk of intestinal helminth and protozoan infection in a refugee population.
AB  - With continuing emigration from endemic countries, screening for parasitic
      infections remains a priority in U.S. communities serving refugee and immigrant
      populations. We report the prevalence of helminths and protozoa as well as
      demographic risk factors associated with these infections among 533 refugees seen
      at the Santa Clara County, California, Refugee Clinic between October 2001 and
      January 2004. Stool parasites were identified from 14% of refugees, including 9%
      found to have one or more protozoa and 6% found to have at least one helminth.
      Most common protozoan infections were Giardia lamblia (6%) and Dientamoeba
      fragilis (3%), and for helminths, hookworm (2%). Protozoa were more frequent in
      refugees < 18 years of age (OR: 2.2 [1.2-4.2]), whereas helminths were more
      common in refugees from South Central Asia (OR: 8.0 [2.3-27.7]) and Africa (OR:
      5.9 [1.6-21.6]) when compared with refugees from Eastern Europe and the Middle
      East. Among helminths, Ascaris lumbricoides and hookworm were concentrated among
      South Central Asians (6 of 7 and 10 of 11 cases, respectively), whereas
      Strongyloides stercoralis was predominantly found in Africans (5 of 7 cases).
      Although predeparture empirical treatment programs in Saharan Africa may have
      helped to reduce prevalence among arriving refugees from this region, parasitic
      infection is still common among refugees to the United States with helminth
      infections found in more specific populations. As refugees represent only a
      fraction of recent immigrants from endemic countries, current studies in
      nonrefugee groups are also needed.

PMID- 16103611
TI  - Hospital-based surveillance for acute febrile illness in Egypt: a focus on
      community-acquired bloodstream infections.
AB  - Acute febrile illness (AFI) is a common syndrome in Egypt. However its etiologies
      are not well characterized. To determine the relative frequency of pathogen
      etiologies and possibly improve diagnostic, clinical management and public health
      measures, we implemented laboratory-based surveillance in a network of infectious
      disease hospitals throughout Egypt. Admitted patients with AFI provided
      background details and a blood sample for bacterial culture and serologic
      analysis. Case definitions were based on laboratory results. Of 10,130 patients
      evaluated between 1999 and 2003, 5% were culture positive for Salmonella enterica
      serogroup Typhi, 3% for Brucella, and 2% for other pathogens. An additional 18%
      of patients had positive serologic results for typhoid and 11% for brucellosis.
      Risk factor analysis identified availability of municipal water to be
      significantly (P < 0.05) associated with protection against typhoid. Animal
      contact and consumption of raw dairy products were significantly associated with
      brucellosis. The surveillance network identified typhoid fever and brucellosis as
      the most common bacterial causes of AFI in Egypt, allowed better description of
      their epidemiology, and may lead to the development of targeted prevention
      strategies.

PMID- 16103612
TI  - Epidemiology of human ehrlichiosis and anaplasmosis in the United States, 2001
      2002.
AB  - During 2001 through 2002, 1,176 cases of the tick-borne diseases human monocytic
      ehrlichiosis (HME) and human granulocytic anaplasmosis (HGA) were reported to the
      Centers for Disease Control and Prevention (CDC) by 32 states through the
      National Electronic Telecommunications System for Surveillance. The average
      reported annual incidences for HME and HGA during 2001-2002 were 0.6 and 1.4
      cases per million population, respectively; incidence was highest among men > 60
      years of age. During this same interval, a total of 883 cases of HME and HGA were
      reported to CDC through a passive surveillance system of tick-borne disease case
      report forms (CRFs). The surveillance information retrieved from CRFs has allowed
      for qualitative evaluation of ehrlichiosis and anaplasmosis risk factors,
      severity, and diagnostic accuracy. Although these surveillance systems likely
      substantially under-represent the true burden of ehrlichiosis and anaplasmosis in
      the United States due to poor recognition and reporting, they represent the first
      compilation of national data since these diseases were made nationally
      notifiable. Continued and improved surveillance activities will progressively
      reinforce our understanding and awareness of these newly recognized zoonotic
      infections.

PMID- 16103613
TI  - High rates of apoptosis in human Mycobacterium ulcerans culture-positive buruli
      ulcer skin lesions.
AB  - Buruli ulcer, a disease caused by Mycobacterium ulcerans, causes ulcerative skin
      disease likely generated by a toxin that mediates apoptosis. We analyzed paraffin
      embedded sections of surgically excised Buruli ulcer lesions (two ulcers and one
      edematous plaque) and adjacent non-lesional skin samples (n = 9) for apoptosis by
      an indirect immunofluorescent terminal deoxynucleotide transferase-mediated dUTP
      digoxigenin nick end labeling (TUNEL) assay. All samples were stained for acid
      fast bacilli (AFB) and cultured for mycobacteria, and most were analyzed with an
      M. ulcerans-specific diagnostic polymerase chain reaction (PCR). TUNEL (+) bodies
      were numerous in both ulcers and the plaque, and sparse or absent in adjacent non
      lesional skin. The AFB tissue stains and cultures for M. ulcerans were positive
      only in the three lesions. The result of the PCR for M. ulcerans was positive in
      all three lesions and in four of six non-lesional tissue samples; three contained
      sparse TUNEL (+) bodies. An abundance of TUNEL (+) bodies in the three AFB stain
      (+), culture (+), and PCR (+) Buruli ulcer lesional samples, but not in nearby
      AFB stain (-), culture (-), and PCR (+) non-lesional skin samples, strengthen the
      evidence that apoptosis is an important tissue destruction mechanism in human
      lesions closely associated with viable M. ulcerans.

PMID- 16103614
TI  - Occurrence of shigellosis in the young and elderly in rural China: results of a
      12-month population-based surveillance study.
AB  - In 2002, population- and treatment center-based surveillance was used to study
      the disease burden of shigellosis in rural Hebei Province in the People's
      Republic of China. A total of 10,105 children with diarrhea or dysentery were
      enrolled. Infants were treated most frequently for diarrhea (1,388/1,000/year)
      followed by children < or = 5 years old (618/1,000/year). Shigellosis was treated
      most often in children 3-4 years old (32/1,000/year) and people > 60 years of age
      (7/1,000/year). Fifty-six percent (184 of 331) Shigella isolates were detected in
      patients who had non-bloody diarrhea. Shigella flexneri was identified in 93% of
      306 isolates. The most common S. flexneri serotypes were 1a (34%), X (33%), and
      2a (28%). More than 90% of the Shigella isolates were resistant to cotrimoxazole
      and nalidixic acid, but remained susceptible to ciprofloxacin, norfloxacin, and
      gentamicin. Widespread resistance to antibiotics adds urgency to the development
      and use of vaccines to control shigellosis.

PMID- 16103615
TI  - Outbreak of severe acute respiratory syndrome in southern Taiwan, 2003.
AB  - This study describes the epidemiologic features of the severe acute respiratory
      syndrome (SARS) outbreak in southern Taiwan in 2003. According to the official
      files of reported cases of SARS from February 21 to June 19, 2003, there were 586
      cases in southern Taiwan. Symptom onset occurred between February 21 and June 19
      in reported cases, between March 13 and May 30 in probable cases, and between
      March 17 and May 23 in polymerase chain reaction (PCR)-positive probable cases.
      Dates of symptom onset were earliest for six imported cases, followed by 53 cases
      related to nosocomial infections and 51 cases without known sources of infection.
      The positive rates of the PCR for these three groups decreased from 50.0% to
      28.3% to 3.9% , respectively (P < 0.001, by chi-square test for linear trend).
      Three other cases resulted from exposure to contaminated hospitals in northern
      Taiwan, one of which was the index case of the nosocomial infection. Imported
      cases following nosocomial infection were the major cause of SARS infections in
      southern Taiwan. Due to the low positive rate of the PCR for SARS coronavirus,
      and the low positive predictive value of reported cases, the factuality of cases
      with unknown sources of infection should be further verified.

PMID- 16103616
TI  - Extended interhuman transmission of monkeypox in a hospital community in the
      Republic of the Congo, 2003.
AB  - This report describes the first reported outbreak of human monkeypox in the
      Republic of Congo. Eleven confirmed and probable monkeypox cases were observed
      during this outbreak, all were less than 18 years old, and most resided on the
      grounds of the Government Hospital in Impfondo. Molecular, virologic, and
      serologic, and diagnostic assays were used to detect evidence of monkeypox (or
      orthopox) virus infection in individuals with striking dermatologic and other
      clinical manifestations. The majority of cases in this outbreak experienced
      significant, symptomatic illnesses; there was one death, possibly involving
      secondary complications, and one instance of profound sequelae. Up to six
      sequential transmissions of monkeypox virus from person to person are
      hypothesized to have occurred, making this the longest uninterrupted chain of
      human monkeypox fully documented to date. The pattern of sustained human-to-human
      transmission observed during this outbreak may influence our current perception
      of the capacity for this zoonotic virus to adapt to humans.

PMID- 16103617
TI  - Comparison of clinical features and hematologic abnormalities between dengue
      fever and dengue hemorrhagic fever among children in the Philippines.
AB  - To demonstrate the differences of clinical features and hematologic abnormalities
      between dengue fever (DF) and dengue hemorrhagic fever (DHF), 359 pediatric
      patients admitted St. Luke's Medical Center in Quezon City, between 1999 and 2001
      in Metro Manila, and adjoining provinces the Philippines, with a laboratory
      confirmed dengue virus infection were evaluated. One third of the patients had
      DHF, and most of these patients were without shock. Restlessness, epistaxis, and
      abdominal pain were more associated with DHF. The platelet count was
      significantly lower in the DHF group than in the DF group before and after
      defervescence. In the DHF patients, the hematocrit was significantly increased
      before defervescence, and decreased the day after due to administration of
      intravenous fluid. Coagulation abnormalities associated with most DHF patients
      were thrombocytopenia and an increased fibrinolysis, but not disseminated
      intravascular coagulation. We present recent data on readily obtained clinical
      and laboratory data that can be used for early diagnosis and consequently earlier
      appropriate treatment of dengue virus infections.

PMID- 16103618
TI  - Endoscopic findings and management of dengue patients with upper gastrointestinal
      bleeding.
AB  - There are 100 million cases of dengue infection, 500,000 cases of dengue
      hemorrhagic fever, and 25,000 deaths annually due to dengue worldwide.
      Gastrointestinal bleeding is the most common type of severe hemorrhage in dengue
      fever. However, there are no reports about the clinical applications of
      endoscopic therapy for upper gastrointestinal bleeding (UGI) in dengue patients.
      From June 17, 2002 to January 30, 2003, 1,156 patients with confirmed dengue
      virus infection were treated at Kaohsiung Chang Gung Memorial Hospital in Taiwan.
      We analyzed those patients who had received endoscopic therapy for UGI. The
      characteristic endoscopic findings, therapeutic courses, and amount of blood
      component transfused were collected from their charts for statistical analysis.
      Among the 1,156 dengue patients, 97 (8.4%) had complications of UGI bleeding
      during hospitalization. The endoscopic findings included hemorrhagic (and/or
      erosive) gastritis in 67% of the patients, gastric ulcer in 57.7%, duodenal ulcer
      in 26.8%, and esophageal ulcer in 3.1%. Of the 73 patients with peptic ulcer, 42
      (57.5%) met the endoscopic criteria (recent hemorrhage) for endoscopic hemostasis
      therapy. Peptic ulcer patients with recent hemorrhage required more transfusions
      with packed red blood cells (P = 0.002) and fresh frozen plasma (P = 0.05) than
      those without recent hemorrhage. Among these 42 patients with recent hemorrhage,
      endoscopic injection therapy was conducted in 15 patients (group A). The other 27
      patients (group B) did not receive endoscopic therapy. After endoscopy, patients
      in group A required more transfusions with packed red blood cells (P = 0.03) and
      fresh frozen plasma (P = 0.014) than did patients in group B. There were no
      significant differences between groups A and B in duration of hospital stay and
      amounts of transfused platelet concentrate after endoscopy. Medical treatment
      with blood transfusion is the mainstay of management of UGI bleeding in dengue
      patients. Patients having peptic ulcer with recent hemorrhage require more
      transfusions with packed red blood cells and fresh frozen plasma for management
      of UGI bleeding than those without recent hemorrhage. However, when peptic ulcer
      with recent hemorrhage is encountered during the endoscopic procedure, endoscopic
      injection therapy is not an effective adjuvant treatment of hemostasis in dengue
      patients with UGI bleeding.

PMID- 16103619
TI  - Potential role of sylvatic and domestic African mosquito species in dengue
      emergence.
AB  - Dengue virus 2 (DENV-2) strains that circulate in sylvatic habitats of Senegal
      and other parts of west Africa are believed to represent ancestral forms that
      evolved into endemic/epidemic strains that now circulate widely in urban areas of
      the tropics. Previous studies suggested that the evolution of the
      endemic/epidemic strains was mediated by adaptation to the peridomestic mosquito
      vectors Aedes aegypti and Ae. albopictus. We conducted experimental infections
      using sylvatic and peridomestic Senegalese mosquitoes, and both sylvatic and
      urban DENV-2 strains to determine if endemic DENV-2 adaptation was vector species
      specific, and to assess ancestral vector susceptibility. Aedes furcifer and Ae.
      luteocephalus, probable sylvatic vectors, were highly susceptible to both
      sylvatic and urban DENV-2 strains. In contrast, sylvatic Ae. vittatus and both
      sylvatic and peridomestic populations of Ae. aegypti were relative refractory to
      all DENV-2 strains tested. These results indicate that adaptation of DENV-2 to
      urban vectors did not result in a loss of infectivity for some African sylvatic
      vectors. Implications for dengue emergence in west Africa are discussed.

PMID- 16103620
TI  - Compartment syndrome: an unusual course for a rare disease.
AB  - We report a case of compartment syndrome of the left upper limb following
      hemorrhage due to Crimean-Congo hemorrhagic fever in a 45-year-old man. As far as
      we know, there is not such a report in the literature. We discuss clinical
      manifestations, electrophysiologic findings, differential diagnosis, and
      management of the patient. A high degree of awareness for an early diagnosis may
      participate to improve the poor prognosis.

PMID- 16103621
TI  - Hepatitis a in Lebanon: a changing epidemiological pattern.
AB  - In this multicenter study in Lebanon, hepatitis A virus (HAV) seroprevalence
      rates were surveyed by age, gender, and socioeconomic factors. Blood samples
      collected from 606 subjects aged 1 to 30 years were analyzed for anti-HAV IgG.
      Age was the most important factor influencing HAV seroprevalence. HAV
      seroprevalence rates in the current study were about 78% in the > or = 21 years
      age group, 28% in the 6-10 years age group, and 11% in the 1-5 years age group as
      compared with 97.7% in adults, 85% in children aged 6-12 years, and 40% in
      children aged 1 to 5 years in previous studies, demonstrating a shift in HAV
      seroprevalence from the younger to the higher age groups. In light of the
      severity of the disease in adults and availability of safe and effective vaccines
      against HAV infection, introduction of HAV vaccination into the national
      immunization schedule of Lebanon should be considered.

PMID- 16103622
TI  - Decline of maternal hepatitis a antibodies during the first 2 years of life in
      infants born in Turkey.
AB  - Selective immunization of at-risk groups may reduce the incidence of hepatitis A
      infection, but only the inclusion of hepatitis A vaccine in a routine universal
      childhood immunization schedule would guarantee control of the infection. But the
      interference by maternally derived hepatitis A antibodies (anti-HAV) with the
      immunogenicity of inactivated hepatitis A vaccine is still important in the
      determination of the optimal age for hepatitis A vaccination. The hepatitis A
      vaccines have not been assessed widely in children under the age of 2 years and
      are not currently licensed for this age group in many countries. A prospective
      trial was performed to detect seroprevalence of maternal hepatitis A antibodies
      during the first 2 years of life among young infants born to hepatitis A antibody
      positive mothers in Turkey. We measured at-birth anti-HAV in 147 infants born in
      our hospital and in their mothers and then from the offspring at months 3, 6, 9,
      12, 15, 18, 21, and 24. The prevalence of seropositivity among the mothers at
      birth were found similarly high (93.9%) to the studies previously done among the
      adults in our area. The prevalence of anti-HAV among children aged 0, 9, 12, 15,
      18, and 21 months were 93.9%, 62.6%, 36.1%, 13.6%, 6.1%, and 0.7%, respectively.
      Although a proportion of infants still had measurable antibodies at 9 and 12
      month of age, two thirds of the infants over the age of 12 months were at high
      risk of acquiring hepatitis A infection, as living in a endemic region.

PMID- 16103623
TI  - Low risk of mother-to-child transmission of hepatitis C virus in Yaounde,
      Cameroon: the ANRS 1262 study.
AB  - To assess mother-to-child transmission (MTCT) of hepatitis C virus (HCV) in
      Cameroon, 5,008 pregnant women were screened for HCV antibodies. Eighty-nine
      (1.8%) were HCV-antibody (HCV-Ab) positive. Among these, 7 (7.9%) were HBsAg
      positive, 6 (6.7%) HIV-positive, and one (1.1%) was co-infected by both hepatitis
      B virus (HBV) and HIV. Sixty-eight (76%) out of 89 HCV-Ab positive pregnant women
      were HCV-RNA positive. The HCV genotype determination indicated the predominance
      of genotype 4 (45.3%), followed by the genotypes 1 (28.1%) and 2 (26.6%). The
      mean HCV-RNA levels of 41 women at the time of delivery was 4.8 (range 0.06-34.7)
      x 10(6) RNA copies/mL. Finally, 35 women delivered 36 live children. None of
      those screened at 6 weeks and 6 months of age were HCV-RNA positive. The failure
      to detect HCV vertical transmission suggests that the mother-to-child
      transmission (MTCT) is not a major route of HCV transmission in Cameroon.

PMID- 16103624
TI  - Experimental and natural infection of North American bats with West Nile virus.
AB  - Big brown (Eptesicus fuscus) and Mexican free-tailed (Tadarida brasiliensis) bats
      were inoculated with the New York 99 strain of West Nile virus to assess their
      potential to serve as amplifying hosts and determine the clinical effect of
      infection. Groups of three or four bats were bled at daily intervals between 1
      and 6 days after inoculation to determine the pattern of viremia. Beginning 2
      days after inoculation, virus was isolated each day from one or more E. fuscus
      bats, in titers ranging from 10 to 180 plaque-forming units per milliliter of
      serum. Virus was not isolated from any of the sera collected from T. brasiliensis
      bats. None of the bats from either species showed clinical signs associated with
      exposure to virus. Sera from an additional 149 bats collected in Louisiana in
      2002 during an epizootic of West Nile fever were tested for antibodies to virus,
      and two were found to be positive. These data suggest that bats from these two
      widely distributed species are unlikely to serve as amplifying hosts for West
      Nile virus.

PMID- 16103625
TI  - Isolation of arboviruses from mosquitoes collected in northern Vietnam.
AB  - In response to recent increases in cases of pediatric encephalitis with unknown
      etiology in northern Vietnam, surveillance for arbovirus activity was conducted
      in four provinces surrounding the city of Hanoi during June 2002 and July-August
      2004. A total of 20,615 mosquitoes consisting of 19 species in 1,122 pools were
      processed for virus isolation; virus isolates were obtained from 44 pools.
      Sagiyama virus (11 isolates), Getah virus (15 isolates), Oya virus (13 isolates),
      and Akabane virus (4 isolates) were identified by immunofluorescence assay and
      sequence analysis of reverse transcription-polymerase chain reaction fragments.
      Surprisingly, no isolates of Japanese encephalitis (JE) virus were obtained.
      Isolation of Akabane virus, Oya virus, Getah virus, and Sagiyama virus is
      reported for the first time from Vietnam.

PMID- 16103626
TI  - Serologic evidence for West Nile virus transmission in Puerto Rico and Cuba.
AB  - During the spring of 2004, approximately 1,950 blood specimens were collected
      from resident and Nearctic-Neotropical migratory birds on the Caribbean islands
      of Puerto Rico and Cuba prior to northerly spring migrations. Eleven birds and
      seven birds, collected in Puerto Rico and Cuba, respectively, showed evidence of
      antibody in a flavivirus enzyme-linked immunosorbent assay. Confirmatory plaque
      reduction neutralization test results indicated neutralizing antibodies to West
      Nile virus in non-migratory resident birds from Puerto Rico and Cuba, which
      indicated local transmission.

PMID- 16103627
TI  - Arsenic contamination in drinking water and skin manifestations in lowland Nepal:
      the first community-based survey.
AB  - A community-based, dose-response study on arsenic contamination was conducted in
      three communities in Terai in lowland Nepal. The arsenic concentration of all the
      tube wells in use (n = 146) and the prevalence of arsenic-induced skin
      manifestation among 1,343 (approximately 80% of the inhabitants) subjects
      indicated the existence of a highly contaminated area in Terai. It was found that
      overall prevalence of arsenicosis among the subjects > or = 15 years old was
      6.9%, which was comparable to those found by the same examiner in arsenic
      contaminated areas in Bangladesh, and that males had prevalence a twice as high
      as females, which could not be explained by the difference in the exposure level.

PMID- 16103628
TI  - Expression of leptin receptors in mononuclear cells from myelodysplastic
      syndromes and acute myeloid leukemias.
AB  - Leptin, the adipocyte hormone, and its receptor have been implicated in the
      differentiation/proliferation of hematopoietic cells. Given that the deregulated
      expression of a variety of growth factors and/or their receptors has been
      implicated in the pathogenesis of certain leukemias, we aimed to characterize the
      potential differences in the expression pattern of the two major leptin receptor
      transcript variants in peripheral blood mononuclear cells (PBMC) between
      different hematologic malignancies. Using RT-PCR and Southern blotting, we
      compared the expression levels of the two major leptin receptors, the longest (OB
      R(L)) and the shortest (OB-R(S)) splice variants, in PBMC from patients with
      myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), healthy individuals
      and two human hematopoietic cell lines (HL-60 and K562). Expression of the OB
      R(S) transcript clearly exceeded that of OB-R(L) in all patients and controls and
      in the HL-60 cells, but this was reversed in the K562 cell line. However, the
      expression of the OB-R(L) was significantly lower in MDS compared to controls and
      tended to be so in AML, while OB-R(S) tended to be higher in MDS and AML patients
      compared to controls, but this difference was not significant. Serum leptin
      levels and circulating soluble leptin receptor levels were slightly but not
      significantly higher in AML and MDS. These alterations in the expression of the
      leptin receptor isoforms in MDS and AML patients could suggest a potential role
      of leptin and its signaling in hematopoietic malignancies, which requires further
      examination.

PMID- 16103629
TI  - Multidrug resistance as a potential prognostic indicator in acute myeloid
      leukemia with normal karyotypes.
AB  - INTRODUCTION: Approximately 45% of adults with acute myeloid leukemia (AML) have
      normal karyotypes and therefore lack structural abnormalities that can assist in
      the localization and characterization of molecular defects. The current study
      attempted to evaluate the potential prognostic role of multidrug resistance
      (MDR), regarded as one of the potential prognostic factors for the outcome of
      overall AML, for AML with normal karyotypes. METHOD AND MATERIALS: A functional
      MDR assay was performed in pretreatment samples from AML patients with normal
      karyotypes. The complete remission (CR) rate, event-free survival (EFS), and
      overall survival (OS) were analyzed according to the MDR status and clinical
      prognostic factors for 88 patients with AML with normal karyotypes. RESULTS: MDR
      by efflux was expressed in 14 out of 48 evaluable patients (29%) but failed to
      identify the association with CR (p = 0.124). However, MDR was identified as an
      independent prognostic factor for EFS and OS (p = 0.013 and 0.046) together with
      the use of stem cell transplantation (p = 0.009 for EFS and 0.029 for OS) and the
      WBC count at presentation (p = 0.023 for EFS and 0.034 for OS). CONCLUSION: The
      functional MDR assay may provide information on the prognosis of AML patients
      with normal karyotypes, and it might be a possible guideline for risk-stratified
      treatment strategies in AML with normal karyotypes.

PMID- 16103630
TI  - Comparative measurement of anti-factor VIII antibody by Bethesda assay and ELISA
      reveals restricted isotype profile and epitope specificity.
AB  - Factor VIII (FVIII) inhibitor antibodies are produced against functional epitopes
      of FVIII in about 30% of severe hemophilia A patients leading to inhibition of
      its procoagulant activity. The Bethesda assay, the most commonly used method to
      measure FVIII inhibitors, based on inhibition of coagulant activity of FVIII, is
      neither able to detect noninhibitory antibodies nor their isotype. In this study
      we employed an indirect enzyme-linked immunosorbent assay (ELISA) to measure dif
      ferent isotypes and IgG subclasses of anti-FVIII anti body in the plasma of
      hemophiliacs (with and without inhibitor) and normal individuals using
      recombinant FVIII-coated microtiter plates. The results showed a predominance of
      IgG and IgG4, though IgA was slightly elevated in a few inhibitor-positive
      patients and IgM was hardly detectable. A highly significant correlation was
      found between the Bethesda titer and the optical density values of total Ig, IgG
      and IgG4 anti-FVIII antibodies obtained by ELISA (p<0.0001). These findings
      suggest a restricted specificity of anti-FVIII response in hemophiliacs towards
      functional epitopes of the molecule. Furthermore, high specificity and reasonable
      sensitivity of the ELISA, together with other technical advantages, suggest this
      method as a suitable supplementary technique for rapid large-scale screening of
      inhibitor-positive samples, though ELISA-negative samples need to be rechecked by
      the Bethesda assay to identify patients with a low inhibitor titer.

PMID- 16103631
TI  - Assessment of megakaryopoiesis in children with acute lymphoblastic leukemia.
AB  - The effect of the underlying disease and chemotherapy on megakaryopoiesis has not
      been extensively studied in children with acute lymphoblastic leukemia (ALL)
      during and at the end of therapy. Using a serum-free assay, we assessed the
      megakaryocyte (Mk) colony formation in vitro from bone marrow mononuclear cells
      of 25 children with ALL during chemotherapy and shortly after the cessation of
      it. Twelve children with solid tumors without bone marrow involvement and cord
      blood from 10 full-term normal vaginal deliveries were used as controls. A
      significant reduction in the number of Mk colonies was observed at diagnosis of
      ALL, and Mk colony formation remained lower than controls throughout the
      different phases of leukemia treatment. Our study suggests that defects in
      megakaryopoiesis of children with ALL in long-term remission may persist during
      chemotherapy and at least shortly after the end of it.

PMID- 16103632
TI  - Increased seroprevalence of human herpesvirus 8 in patients with hematological
      disorders.
AB  - Human herpesvirus 8 (HHV8) has been consistently linked to Kaposi's sarcoma and
      many hematological diseases such as pleural effusion lymphoma, multicentric
      Castleman's disease, some lymphoproliferative diseases and posttransplantation
      bone marrow failure. However, whether patients with hematological disorders are
      at a higher risk of HHV8 infection has not been determined. In this study,
      indirect immunofluorescence was used to detect antibodies against lytic antigens
      of HHV8 in 265 patients with hematological disorders. Our data showed that 24.5%
      of patients (65/265) were seropositive for HHV8 IgG antibody, which was
      significantly higher than in our general population (p < 0.001). A significantly
      higher seropositive rate can be found in patients with lymphoma, leukemia,
      autoimmune cytopenias and myeloproliferative disorders, but not in patients with
      myeloma or aplastic anemia. No difference in the seropositive rate is associated
      with gender or age. We conclude that some patients with hematological disorders
      are at a higher risk of HHV8 infection.

PMID- 16103633
TI  - Clinical correlation of bone marrow microvessel density in essential
      thrombocythemia.
AB  - The aim of this study was to investigate the prognostic relevance of angiogenesis
      expressed as bone marrow microvessel density (MVD) in 40 patients with essential
      thrombocythemia (ET). Bone marrow MVD was visualized in paraffin tissue sections
      using immunohistochemical staining for CD34 protein. Increased MVD of bone marrow
      specimens was not significantly correlated with clinical (sex, age, microvascular
      disturbances, liver and spleen size, complications, treatment or no before
      biopsy), laboratory (peripheral blood count), bone marrow histopathological
      parameters (cellularity, megakaryocyte clumping and reticulin fibrosis) and
      overall survival. These preliminary findings suggest that angiogenesis has no
      prognostic value in patients with ET.

PMID- 16103634
TI  - A case of chronic myelomonocytic leukemia with severe eosinophilia having
      t(5;12)(q31;p13) with t(1;7)(q10;p10).
AB  - We describe an unusual case of chronic myelomonocytic leukemia with severe
      eosinophilia having t(5;12)(q31;p13) with t(1;7)(q10;p10). The eosinophilic
      proliferation was severe in peripheral blood and bone marrow, and they revealed
      marked dysplastic features. We performed fluorescence in situ hybridization
      (FISH) and immunohistochemistry to evaluate the clonality of eosinophils. The
      eosinophils were stained positively to platelet-derived growth factor receptor
      beta. By FISH using chromosome 1 satellite probe and chromosome 1q telomere
      probe, the eosinophils were proved to belong to the malignant clone.

PMID- 16103635
TI  - Angioimmunoblastic T cell lymphoma with an unusual proliferation of Epstein-Barr
      virus-associated large B cells arising in a patient with progressive systemic
      sclerosis.
AB  - We report an unusual case of angioimmunoblastic T cell lymphoma arising in the
      setting of 5 years of immunosuppressive treatment for progressive systemic
      sclerosis. The lymph node lesion was accompanied by large blastic B cells with an
      association of Epstein-Barr virus. Southern blot study demonstrated the clonal
      rearrangement of T cell receptor beta-chain gene, but not of immunoglobulin heavy
      chain gene. Phenotypical examination of the lymph node also revealed the
      predominance of CD4+ T cells in addition to the proliferation of follicular
      dendritic cells, but no light chain restriction in large B cell components. In
      the clinical and laboratory aspects, neutrophilia (15.8 x 10(9)/l) and
      plasmacytosis (40%) in bone marrow were noted, which were considered to be
      closely related to elevated serum granulocyte colony-stimulating factor,
      interleukin (IL)-4 and IL-6. Based on the combined data described here, our
      preferred diagnosis was angioimmunoblastic T cell lymphoma with Epstein-Barr
      virus-associated B cell lymphoproliferative disorder, the pathogenesis of which
      was suggested to be closely associated with immunosuppressive treatment for
      progressive systemic sclerosis.

PMID- 16103636
TI  - Dyserythropoietic anemia and thrombocytopenia due to a novel mutation in GATA-1.
AB  - Hematopoiesis is a complex process regulated by nuclear proteins that coordinate
      lineage-specific patterns of gene expression. Targeted mutagenesis has revealed
      critical roles for the X-linked transcription factor GATA-1 in erythrocyte and
      megakaryocyte differentiation. GATA-1 has two zinc fingers essential for normal
      function. The C-terminal finger is necessary for DNA binding. The N-terminal
      finger mediates interaction with FOG-1, a cofactor for GATA-1. Mutations in the N
      terminal zinc finger of GATA-1 result in abnormal hematopoiesis. Here we report a
      family with a novel single base mutation that results in an amino acid
      substitution (Gly208Arg) within the highly conserved portion of the GATA-1 N
      terminal finger domain, leading to dyserythropoietic anemia and
      macrothrombocytopenia. Another mutation described at the same codon (208) has
      been found to be associated with thrombocytopenia only. Our data support and
      extend the effect of the amino acid substitution at codon 208 on GATA-1 function
      not only regarding megakaryocyte but also regarding erythroid development.

PMID- 16103637
TI  - Expression profile of genes representing varied spectra of cell lineages in human
      umbilical cord blood-derived mesenchymal stem cells.

PMID- 16103638
TI  - Altered growth characteristics of cord blood cells after in vivo exposure to
      maternal acute myeloid leukemia and chemotherapy.

PMID- 16103639
TI  - Relationship between molecular variants and clinical manifestions in twelve
      glucose-6-phosphate dehydrogenase-deficient patients in Jordan.

PMID- 16103640
TI  - Consortium of otolaryngology-head and neck surgery journals to collaborate in
      maintenance of high ethical standards.

PMID- 16103641
TI  - Sketches of otohistory. Part 10: noise-induced hearing loss.

PMID- 16103643
TI  - A guinea pig strain with recessive heredity of deafness, producing normal-hearing
      heterozygotes with resistance to noise trauma.
AB  - A new strain of waltzing guinea pigs arose spontaneously in a guinea pig breeding
      facility in Germany in 1996. In addition to obvious vestibular dysfunction, the
      waltzing animals appear deaf already at birth. Histological analysis revealed
      that the waltzers lack an open scala media due to the collapse of Reissner's
      membrane onto the surface of the hearing organ. Subsequent breeding has shown
      that this strain has a recessive mode of inheritance. The homozygotes are deaf
      and display a waltzing behaviour throughout their lives while the heterozygotes
      show no significant signs of inner ear injury despite being carriers of this
      specific mutated gene of hearing impairment. However, the heterozygous animals
      offer the opportunity to study how hereditary factors interact with auditory
      stress. In the present study, the susceptibility of the carriers to noise was
      investigated. Auditory brainstem responses were obtained prior to and after noise
      exposure (4 kHz, 110 dB, 6 h). The carriers were significantly less affected by
      the noise as compared to control animals. This difference was still significant
      at 4 weeks following noise exposure. It is suggested that the heterozygous
      animals have an endogenous resistance to auditory stress.

PMID- 16103642
TI  - In silico analysis of 2085 clones from a normalized rat vestibular periphery 3'
      cDNA library.
AB  - The inserts from 2400 cDNA clones isolated from a normalized Rattus norvegicus
      vestibular periphery cDNA library were sequenced and characterized. The Wackym
      Soares vestibular 3' cDNA library was constructed from the saccular and utricular
      maculae, the ampullae of all three semicircular canals and Scarpa's ganglia
      containing the somata of the primary afferent neurons, microdissected from 104
      male and female rats. The inserts from 2400 randomly selected clones were
      sequenced from the 5' end. Each sequence was analyzed using the BLAST algorithm
      compared to the Genbank nonredundant, rat genome, mouse genome and human genome
      databases to search for high homology alignments. Of the initial 2400 clones, 315
      (13%) were found to be of poor quality and did not yield useful information, and
      therefore were eliminated from the analysis. Of the remaining 2085 sequences, 918
      (44%) were found to represent 758 unique genes having useful annotations that
      were identified in databases within the public domain or in the published
      literature; these sequences were designated as known characterized sequences.
      1141 sequences (55%) aligned with 1011 unique sequences had no useful annotations
      and were designated as known but uncharacterized sequences. Of the remaining 26
      sequences (1%), 24 aligned with rat genomic sequences, but none matched
      previously described rat expressed sequence tags or mRNAs. No significant
      alignment to the rat or human genomic sequences could be found for the remaining
      2 sequences. Of the 2085 sequences analyzed, 86% were singletons. The known,
      characterized sequences were analyzed with the FatiGO online data-mining tool
      (http://fatigo.bioinfo.cnio.es/) to identify level 5 biological process gene
      ontology (GO) terms for each alignment and to group alignments with similar or
      identical GO terms. Numerous genes were identified that have not been previously
      shown to be expressed in the vestibular system. Further characterization of the
      novel cDNA sequences may lead to the identification of genes with vestibular
      specific functions. Continued analysis of the rat vestibular periphery
      transcriptome should provide new insights into vestibular function and generate
      new hypotheses. Physiological studies are necessary to further elucidate the
      roles of the identified genes and novel sequences in vestibular function.

PMID- 16103644
TI  - Psychophysical metrics and speech recognition in cochlear implant users.
AB  - Intersubject variability in perception is a prominent characteristic of people
      with cochlear implants. This study characterized intersubject differences using
      simple metrics based on psychophysical measures: maximum comfortable loudness
      levels (C levels) and dynamic ranges (DRs). In a group of 17 subjects, we
      assessed across-site variation (ASV) and across-site mean (ASM) values of C
      levels and DRs for bipolar (BP) and monopolar (MP) stimulation, and examined the
      relation of these metrics to speech recognition across subjects. Significant
      negative correlations with speech recognition were found for ASVs of C levels for
      BP stimulation; i.e., subjects with high ASVs of BP C levels had poor speech
      recognition. Positive correlations with speech recognition were found for ASMs of
      C levels and ASMs of DRs for both BP and MP stimulation; i.e., subjects with high
      mean C levels and large mean DRs had better speech recognition. Thus, these
      psychophysical metrics are effective for diagnosis of individual differences in
      performance of subjects with cochlear implants. Furthermore, they point to some
      potentially useful treatment procedures.

PMID- 16103645
TI  - Minimum audible angle, just noticeable interaural differences and speech
      intelligibility with bilateral cochlear implants using clinical speech
      processors.
AB  - Sound localization and speech intelligibility were assessed in 5 patients
      implanted bilaterally with Medel C40+ or Medel C40 cochlear implant (CI) systems.
      The minimum audible angle (MAA) around the head in the horizontal plane was
      assessed in patients with bilateral CI using white noise bursts of 1000 ms
      duration presented from a loudspeaker mounted on a rotating boom and compared
      with the MAA of age-matched normal hearing controls. Spatial discrimination was
      found to be good in front and in the back of the head with near-normal MAA values
      (patients: 3-8 degrees , controls: 1-4 degrees ). In contrast, poor performance
      on the sides was found (patients: 30 to over 45 degrees , controls 7-10 degrees
      ). Bilateral CI significantly improved spatial discrimination in front for all
      patients, when compared with the use of either CI alone. Just noticeable
      differences (JNDs) in interaural intensity and time were assessed using white
      noise bursts (1000 ms duration; 50 ms linear ramp). In addition, interaural time
      JNDs were assessed using click trains (800 ms duration, 40 mus clicks, 50 Hz) and
      noise bursts in which either only the envelope or only the fine structure was
      shifted in time. In comparison with normal hearing controls, patients with
      bilateral CI showed near-normal interaural intensity JNDs but substantially
      poorer interaural time JNDs depending on the type of stimulus. In contrast to
      envelope onset/offset cues, interaural fine structure time differences were not
      perceived by the patients using CI systems employing the continuous interleaved
      sampling strategy without synchronization between their pulse stimulation times.
      Speech intelligibility in quiet and CCITT noise from the side (+/-90 degrees )
      was assessed using the German HSM sentence test and was significantly better when
      using bilateral CI in comparison with either unilateral CI, mainly due to a head
      shadow effect. These favorable results are in agreement with the patients'
      subjective experiences assessed with a questionnaire and support the use of
      bilateral CI.

PMID- 16103646
TI  - Incontinentia pigmenti in combination with decreased IgG subclass concentrations
      in a female newborn.
AB  - Incontinentia pigmenti (IP) is a rare neurocutaneous disorder caused by mutations
      in the NEMO (NF-kappaB essential modulator) gene. Skin lesions are typically the
      first manifestation of IP though they may be accompanied by multiple
      malformations. This report presents the case of a female newborn with early onset
      of IP lesions within the 1st day of life. After the age of 1 month she developed
      frequent episodes of severe gastroenteritis. Examination of the immune system
      revealed low concentrations of IgG subclasses. This study suggests that, contrary
      to previous belief, IP is associated with immune deficiency.

PMID- 16103647
TI  - Comments on 'when to measure lipid profile after stroke'.

PMID- 16103648
TI  - Patricia Ann Jacobs.

PMID- 16103649
TI  - Chromosomics.
AB  - The term "chromosomics" is introduced to draw attention to the three-dimensional
      morphological changes in chromosomes that are essential elements in gene
      regulation. Chromosomics deals with the plasticity of chromosomes in relation to
      the three-dimensional positions of genes, which affect cell function in a
      developmental and tissue-specific manner during the cell cycle. It also deals
      with species-specific differences in the architecture of chromosomes, which has
      been overlooked in the past. Chromosomics includes research into chromatin
      modification-mediated changes in the architecture of chromosomes, which may
      influence the functions and life-spans of cells, tissues, organs and individuals.
      It also addresses the occurrence and prevalence of chromosomal gaps and breaks.

PMID- 16103650
TI  - Transcriptomic analyses support the similarity of gene expression between brain
      and testis in human as well as mouse.
AB  - We previously revealed similarity in gene expression patterns between human brain
      and testis, based on digital differential display analyses of 760 human Unigenes.
      In the present work, we reanalyzed the gene expression data in many tissues of
      human and mouse for a large number of genes almost covering the respective whole
      genomes. The results indicated that both in human and in mouse, the gene
      expression profiles exhibited by brain, cerebellum and testis are most similar to
      each other compared with other tissues.

PMID- 16103651
TI  - Analysis of the genomic region containing the tammar wallaby (Macropus eugenii)
      orthologues of MHC class III genes.
AB  - Major histocompatibility complex (MHC) molecules are central to development and
      regulation of the immune system in all jawed vertebrates. MHC class III cytokine
      genes from the tumor necrosis factor core family, including tumor necrosis factor
      (TNF) and lymphotoxin alpha and beta (LTA, LTB), are well studied in human and
      mouse. Orthologues have been identified in several other eutherian species and
      the cDNA sequences have been reported for a model marsupial, the tammar wallaby.
      Comparative genomics can help to determine gene function, to understand the
      evolution of a gene or gene family, and to identify potential regulatory regions.
      We therefore cloned the genomic region containing the tammar LTB, TNF, and LTA
      orthologues by "genome walking", using primers designed from known tammar
      sequences and regions conserved in other species. We isolated two tammar BAC
      clones containing all three genes. These tammar genes show similar intergenic
      distances and the same transcriptional orientation as in human and mouse. Gene
      structures and sequences are also very conserved. By comparing the tammar, human
      and mouse genomic sequences we were able to identify candidate regulatory regions
      for these genes in mammals. Full length sequencing of BACs containing the three
      genes has been partially completed, and reveals the presence of a number of other
      tammar MHC III orthologues in this region.

PMID- 16103652
TI  - A comparative genetic map of the turkey genome.
AB  - Genetic markers (microsatellites and SNPs) were used to create and compare maps
      of the turkey and chicken genomes. A physical map of the chicken genome was built
      by comparing sequences of turkey markers with the chicken whole-genome sequence
      by BLAST analysis. A genetic linkage map of the turkey genome (Meleagris
      gallopavo) was developed by segregation analysis of genetic markers within the
      University of Minnesota/Nicholas Turkey Breeding Farms (UMN/NTBF) resource
      population. This linkage map of the turkey genome includes 314 loci arranged into
      29 linkage groups. An additional 40 markers are tentatively placed within linkage
      groups based on two-point LOD scores and 16 markers remain unlinked. Total map
      distance contained within linkage groups is 2,011 cM with the longest linkage
      group (47 loci) measuring 413.3 cM. Average marker interval over the 29 linkage
      groups was 6.4 cM. All but one turkey linkage group could be aligned with the
      physical map of the chicken genome. The present genetic map of the turkey
      provides a comparative framework for future genomic studies.

PMID- 16103653
TI  - Chromosomal localization of seven HSA3q13-->q23 NotI linking clones on chicken
      microchromosomes: orthology of GGA14 and GGA15 to a gene-rich region of HSA3.
AB  - Double-color fluorescence in situ hybridization was performed on chicken
      chromosomes using seven unique clones from the human chromosome 3-specific NotI
      linking libraries. Six of them (NL1-097, NL2-092, NL2-230, NLM-007, NLM-118, and
      NLM-196) were located on the same chicken microchromosome and NL1-290 on another.
      Two chicken microchromosome GGA15-specific BAC clones, JE024F14 containing the
      IGVPS gene and JE020G17 containing the ALDH1A1 gene, were cytogenetically mapped
      to the same microchromosome that carried the six NotI linking clones, allowing
      identification of this chromosome as GGA15. Two GGA14-specific clones, JE027C23
      and JE014E08 containing the HBA gene cluster, were co-localized on the same
      microchromosome as NL1-290, suggesting that this chromosome was GGA14. The
      results indicated that the human chromosomal region HSA3q13-->q23 is likely to be
      orthologous to GGA15 and GGA14. The breakpoint of evolutionary conservation of
      human and chicken chromosomes was detected on HSA3q13.3-->q23 between NL1-290, on
      the one hand, and six other NotI clones, on the other hand. Considering the
      available chicken-human comparative mapping data, another breakpoint appears to
      exist between the above NotI loci and four other genes, TFRC, EIF4A2, SKIL and
      DHX36 located on HSA3q24-->qter and GGA9. Based on human sequences within the
      NotI clones, localization of the six new chicken coding sequences orthologous to
      the human/rodent genes was suggested to be on GGA15 and one on GGA14.
      Microchromosomal location of seven NotI clones from the HSA3q21 T-band region can
      be considered as evidence in support of our hypothesis about the functional
      analogy of mammalian T-bands and avian microchromosomes.

PMID- 16103654
TI  - Expanded comparative mapping between man and rabbit and detection of a new
      conserved segment between HSA22 and OCU4.
AB  - Rabbit, a domestic species exploited both in animal production and medical
      research has only recently begun to be included in gene mapping projects, in
      particular by the French National Institute of Agronomics. By 2002, less than 60
      genes had been precisely localised on rabbit chromosomes, which led us to start a
      large-scale project on gene mapping in rabbit with the publication of 133 gene
      localisations in 2003 (Chantry-Darmon et al., 2003). Here, we report the
      localisation of 102 new genes resulting in good coverage of the rabbit genome and
      an eight-fold enrichment of the gene map. In addition, we have detected a new
      conserved segment between rabbit chromosome 4q15.3 and part of human chromosome
      22 and thus improved the comparative map with the human genome.

PMID- 16103655
TI  - The canine sarcoglycan delta gene: BAC clone contig assembly, chromosome
      assignment and interrogation as a candidate gene for dilated cardiomyopathy in
      Dobermann dogs.
AB  - Dilated cardiomyopathy (DCM) is a common disease of the myocardium recognized in
      human, dog and experimental animals. Genetic factors are responsible for a large
      proportion of cases in humans, and 17 genes with DCM causing mutations have been
      identified. The genetic origin of DCM in the Dobermann dogs has been suggested,
      but no disease genes have been identified to date. In this paper, we describe the
      characterization and evaluation of the canine sarcoglycan delta (SGCD), a gene
      implicated in DCM in human and hamster. Bacterial artificial chromosomes (BACs)
      containing the canine SGCD gene were isolated with probes for exon 3 and exons 4
      8 and were characterized by Southern blot analysis. BAC end sequences were
      obtained for four BACs. Three of the BACs overlapped and could be ordered
      relative to each other and the end sequences of all four BACs could be anchored
      on the preliminary assembly of the dog genome sequence (www. ensembl.org). One of
      the BACs of the partial contig was localized by fluorescent in situ hybridization
      to canine chromosome 4q22, in agreement with the dog genome sequence. Two highly
      informative polymorphic microsatellite markers in intron 7 of the SGCD gene were
      identified. In 25 DCM-affected and 13 non DCM-affected dogs seven different
      haplotypes could be distinguished. However, no association between any of the
      SGCD variants and the disease locus was apparent.

PMID- 16103656
TI  - Cytogenetic comparison of saola (Pseudoryx nghetinhensis) and cattle (Bos taurus)
      using G- and Q-banding and FISH.
AB  - In order to cytogenetically describe the new bovid species saola (Pseudoryx
      nghetinhensis), comparative G- and Q-banding of saola and cattle (Bos taurus)
      chromosomes as well as FISH-mapping of 32 type-I markers (29 Texas markers and
      three additional markers) on saola chromosomes were performed. Saola was shown to
      have a diploid number of 2n = 50 chromosomes possessing five biarmed autosomal
      pairs and an acrocentric X chromosome. Homology of saola and cattle chromosomes
      was indicated by banding patterns and by marker hybridization suggesting that all
      five biarmed pairs in saola originate from centric fusions involving ten cattle
      autosomes. However, small intrachromosomal rearrangements cannot be excluded. In
      this study the first preliminary homology map of these two species is presented.

PMID- 16103657
TI  - Karyotypic evolution and organization of the highly repetitive DNA sequences in
      the Japanese shrew-moles, Dymecodon pilirostris and Urotrichus talpoides.
AB  - The karyological relationship and organization of highly repetitive DNA sequences
      in Japanese shrew-moles were studied by zoo-blot hybridization and fluorescence
      in situ hybridization (FISH). When the genomic DNA of the eastern race of
      Urotrichus talpoides was digested with PstI, three fragments of highly repetitive
      DNA sequences, approximately 0.7, 0.9, and 1.4 kb in length, were observed as
      distinct bands. The results of FISH in the eastern race of U. talpoides using
      these three fragments separately as probes showed that the 0.7-kb PstI fragment
      was distributed in the centromeric regions of most chromosomes, and that the 0.9-
      and 1.4-kb fragments were predominantly located in the C-heterochromatin region
      of chromosome 13p. Although the western race of U. talpoides also had three PstI
      fragments, 0.9- and 1.4-kb PstI fragments were more ambiguous than those of the
      eastern race. The PstI- digested genomic DNA in Dymecodonpilirostris produced
      only a faint 0.9-kb band, and its signal patterns obtained by zoo-blot
      hybridization were clearly different from those of U. talpoides. The 0.7-kb
      fragment of U. talpoides hybridized strongly with the 0.9-kb fragment of D.
      pilirostris. In a FISH analysis, the 0.9-kb fragment of D. pilirostris hybridized
      with highly repetitive DNA in the centromeric regions of most chromosomes from
      both D. pilirostris and U. talpoides. Zoo-blot hybridization and FISH analyses
      suggest that the 0.9- and 1.4-kb PstI fragments were generated specifically in
      the genome of U. talpoides after the common ancestor differentiated into two
      extant shrew-mole species. A difference in the length of the centromeric elements
      between U. talpoides and D. pilirostris might be observed due to certain
      modifications of the repeating unit.

PMID- 16103658
TI  - Heterochromatin differentiation shows the pathways of karyotypic evolution in
      Israeli mole rats (Spalax, Spalacidae, Rodentia).
AB  - C-banding, base-specific fluorochrome staining (CMA3/DA/DAPI), and comparative
      genomic hybridization (CGH) were used to analyze the constitutive heterochromatin
      in two Israeli Spalax species, S. galili (2n = 52) and S. judai (2n = 60). It was
      shown that C-positive centromeric heterochromatin and some telomeric sites
      comprise GC-rich DNA sequences in both species. Comparative genomic in situ
      hybridization revealed slight qualitative differences in highly repetitive
      sequences in the two Spalax species. Eight acrocentric pairs in S. judai that are
      involved in Robertsonian rearrangements, possessed composite heterochromatin with
      a preference of S. judai highly repetitive sequences in the proximal region.
      Heterochromatin of the sex chromosomes, two biarmed homologous pairs (4 and 5) in
      both species, and acrocentric chromosomes from the group with a variable
      centromere position in S. judai was entirely species-specific. The high level of
      homology in the composition of heterochromatin may relate to the recent
      divergence of Israeli Spalax. Interspecies heterochromatin differences are
      discussed in the context of possible mechanisms in the Spalax chromosome
      evolution.

PMID- 16103659
TI  - Identification of the sex chromosome pair in coho salmon (Oncorhynchus kisutch):
      lack of conservation of the sex linkage group with chinook salmon (Oncorhynchus
      tshawytscha).
AB  - Fluorescence in situ hybridization (FISH) using a probe to the male-specific GH-Y
      (growth hormone pseudogene) was used to identify the Y chromosome in coho salmon
      (Oncorhynchus kisutch). The sex chromosome pair is morphologically similar to
      chinook salmon (Oncorhynchus tshawytscha) with the GH-Y localized to the small
      short arm of the largest subtelocentric chromosome pair. FISH experiments with
      probes containing sex-linked genes in rainbow trout (Oncorhynchus mykiss)
      (SCAR163) and chinook salmon (Omy7INRA) showed that the coho sex linkage group is
      different from chinook and rainbow trout and this was confirmed by segregation
      analysis for the Omy7INRA locus. The telomeric location of the SEX locus, the
      presence of shared male-specific markers in coho and chinook salmon, and the lack
      of conservation of sex-linkage groups suggest that transposition of a small male
      specific region may have occurred repeatedly in salmonid fishes of the genus
      Oncorhynchus.

PMID- 16103660
TI  - Three cases with rare interstitial rearrangements of chromosome 1 characterized
      by multicolor banding.
AB  - In this report, we describe three unrelated patients with similar symptoms such
      as mental retardation, growth delay and multiple phenotypic abnormalities. GTG
      banding analysis revealed karyotypes with add(1p) in two cases and an add(1q) in
      the third. Fluorescence in situ hybridization (FISH) analysis using high
      resolution multicolor banding (MCB) characterized the aberrations of the abnormal
      chromosomes 1 as a (sub)terminal duplication and inverted duplications,
      respectively. Although three different chromosomal regions i.e. 1p36.1, 1p36.2-
      >1p31.3 and 1q41-->1q44 were involved, all three patients had similar patterns of
      dysmorphic findings. These cases demonstrate the power of MCB in the
      characterization of small interstitial chromosomal aberrations and resulted in
      the characterization of three previously unreported congenital chromosome 1
      rearrangements.

PMID- 16103661
TI  - Molecular cytogenetic characterization of ring chromosome 4 in a female having a
      chromosomally normal child.
AB  - We present the clinical and molecular findings of mosaic ring chromosome 4. The
      patient was referred to us for infertility and short stature. Results of three
      repeated cytogenetic analyses from lymphocytes showed a similar mosaic karyotype
      with multiple cell-lines [46,XX,r(4)/45,XX,-4/46,XX,dic
      r(4)/47,XX,r(4),+r(4)/46,XX]. FISH showed deletion of the 4p subtelomeric region
      and the 4q telomeric region from the ring chromosome 4. The breakpoints were
      mapped using molecular analysis. Parental karyotypes were normal. During the
      course of this study, the patient became pregnant without assisted reproductive
      technology. The result of amniocentesis performed at 16 weeks gestation showed a
      normal karyotype. Delivery was uncomplicated. This is the first report, to our
      knowledge, of the presence of ring chromosome 4 having various mosaic conditions
      in a female having a chromosomally normal fetus.

PMID- 16103662
TI  - Unusual small supernumerary marker chromosome (sSMC) 9 in a Klinefelter patient.
AB  - Small supernumerary marker chromosomes (sSMC) are small additional chromosomes
      characterizable for their origin only by molecular cytogenetic approaches. sSMC
      have been reported previously in four types of syndromes associated with
      chromosomal imbalances: in approximately 150 cases with Turner syndrome, 26 cases
      with Down syndrome and only one case each with Klinefelter syndrome and "Triple
      X"-syndrome. Here we report the second case with an sSMC detected in addition to
      a Klinefelter karyotype. Molecular cytogenetics applying centromere-specific
      multicolor FISH (cenM-FISH) and a specific subcentromere-specific (subcenM-FISH)
      probe set characterized the sSMC as a dic(9)(:p12-->q11.1::q11.1--> p11.1:). The
      reported patient was described with hypogonadism, gynaecomastia plus a bronchial
      carcinoma. The patient's clinical features are discussed in connection with other
      Klinefelter cases and possible consequences of presence of the sSMC(9).
      Furthermore, a suggestion is made for the mode of sSMC-formation in this case.

PMID- 16103663
TI  - Pure trisomy 19p syndrome in an infant with an extra ring chromosome.
AB  - We report a 12-month-old infant evaluated for severe hypotonia, psychomotor
      retardation, and facial dysmorphisms, including round face, high prominent
      forehead, downward slanted palpebral fissures, hypertelorism, short nose, chubby
      cheeks, long philtrum, anteverted lower lip, low-set asymmetric and dysmorphic
      ears. Karyotype analysis disclosed an extra mosaic ring chromosome, which
      included the whole 19p arm. Four additional patients with supernumerary ring 19
      chromosomes have been reported, but none of them had pure trisomy 19p.

PMID- 16103664
TI  - Current guidelines for the treatment of severe pneumonia and sepsis.
AB  - Infections in intensive care unit (ICU) patients like severe pneumonia, e.g.
      nosocomial (NP) and community-acquired pneumonia (CAP), or septicemia must be
      treated promptly and effectively because of the ensuing high mortality. Treatment
      is thus empirical and starts before the results of microbiological cultures are
      known. The risk factors affecting mortality include severity of illness,
      virulence of etiologic pathogens and the use of inappropriate antibiotic therapy.
      Several studies have shown that modifying initially inadequate therapy, according
      to microbiological results, does not result in a better outcome. Due to this,
      antibiotic treatment requires agents which have an appropriate spectrum covering
      the likely pathogens causing these infections. In critically ill patients, the
      need for empirical first-line treatment covering a broad spectrum of Gram
      negative and Gram-positive bacteria, as recommended in international guidelines
      (e.g. those of the American Thoracic Society or the Infectious Diseases Society
      of America), is justified in the presence of resistant organisms commonly
      documented in these patients. To choose an appropriate, initial antibiotic
      regimen, local and national resistance data have to be considered. With respect
      to new German resistance trends in Gram-negative and Gram-positive bacteria, the
      Paul Ehrlich Society of Chemotherapy has recently published guidelines for the
      treatment of infections in hospitalized patients. Especially in ICU patients with
      severe pneumonia (NP or CAP) or septicemia and risk factors like underlying
      diseases, antibiotic pretreatment or mechanical ventilation, agents with an
      appropriate spectrum encompassing Pseudomonas aeruginosa as well as other Gram
      negative bacteria like Escherichia coli, Klebsiella spp., Enterobacter spp. and
      Gram-positive bacteria (e.g. Staphylococcus aureus, pneumococci and streptococci)
      are recommended as treatment of choice. Combination therapy with an anti
      pseudomonal beta-lactam and a fluoroquinolone or an aminoglycoside are
      recommended for these patients to provide the necessary spectrum of activity and
      to prevent the emergence of resistant organisms. On the other hand, clinical
      trials and meta-analyses have shown the efficacy, tolerability and cost
      effectiveness of monotherapy regimens even in critically ill and
      immunocompromised patients. CONCLUSION: Appropriate beta-lactam antibiotics
      recommended in international and German guidelines for the treatment of severe
      CAP, NP and septicemia, either as monotherapy or as combination therapy, are the
      4th generation cephalosporin cefepime, the carbapenems imipenem and meropenem,
      and the acylamino-beta-lactamase inhibitor combination piperacillin-tazobactam.

PMID- 16103665
TI  - From Atoxyl to Salvarsan: searching for the magic bullet.
AB  - March 15th of 2004 marked the 150th anniversary of the birth of Paul Ehrlich. He
      was the founder of modern chemotherapy and in fact coined the word and invented
      the science of chemical therapy. He and his chemist Al fred Bertheim were the
      first people to do three things: (1) identify a substance, either man-made or
      from natural products, which showed promise in killing certain invading
      organisms; (2) determine the correct structure of the active compound in this
      substance, and (3) modify the chemical structure of this compound to make it more
      potent to invading organisms and less harmful to the host.

PMID- 16103666
TI  - Antimicrobial activities of seven novel tetramethylpiperidine-substituted
      phenazines against multiple-drug-resistant Gram-positive bacteria.
AB  - BACKGROUND: A dramatic increase in multiple-drug-resistant (MDR) Gram-positive
      pathogens has occurred in recent times, leading to increased rates or morbidity
      and mortality and also associated with high costs for the treatment of these
      infections. It is clear that there is an urgent need for the development of
      effective antimicrobial agents. The anti-bacterial activity of seven 2,2,6,6
      tetramethylpiperidine (TMP)-substituted phenazines, compared to clofazimine
      (B663), were tested against 70 clinical isolates of methicillin-resistant
      Staphylococcus aureus, MDR Streptococcus pneumoniae and resistant Enterococcus
      sp. METHODS: Standard minimum inhibitory concentration agar dilution
      susceptibility tests were done on all isolates, including ATCC control strains.
      RESULTS: All the TMP-substituted phenazines were more active than clofazimine
      against all isolates tested. Compound B4125 was the most active by inhibiting all
      growth of the organisms tested, including vancomycin-resistant Enterococcus
      faecium. CONCLUSION: Clofazimine has been shown to have anti-staphylococcal
      activity. We demonstrate enhanced anti-bacterial activity of TMP-substituted
      phenazines against drug-resistant Gram-positive organisms compared to
      clofazimine.

PMID- 16103667
TI  - Alprazolam significantly improves the efficacy of granisetron in the prophylaxis
      of emesis secondary to moderately emetogenic chemotherapy in patients with breast
      cancer.
AB  - BACKGROUND: Alprazolam, a newer benzodiazepine, may be useful in the control of
      nausea and vomiting in breast cancer patients. METHODS: Nineteen operable breast
      cancer patients were included in this randomized prospective crossover open-label
      trial. Patients received either granisetron (G) alone, or in combination with
      alprazolam (A). Group A patients received G+A first and then crossed over to G
      alone after the 2nd or 3rd cycle. Group B patients received the reverse order.
      Eighty-four cycles were evaluated. RESULTS: In group A, complete remission (CR)
      plus major response (MR) was higher (93.9%) with G+A than with G-alone (83.3%; p
      = 0.0001) in the first 24-hour period. In group B, CR plus MR was higher in G+A
      cycles (100%) than in G-alone cycles (85.7%; p = 0.035) in the 24-hour period and
      in the 25- to 129-hour period (92 vs. 90.5%, respectively; p = 0.022).
      CONCLUSION: Alprazolam increases the efficacy of granisetron in patients with
      breast cancer treated with an anthracycline-containing regimen.

PMID- 16103668
TI  - Perceived work performance of patients who experienced an acute coronary syndrome
      event.
AB  - The objectives of this study were to describe the perceived work performance of
      patients previously diagnosed with acute coronary syndrome (ACS) and to determine
      the relationship between patient-specific variables and perceived work
      performance. This cross-sectional study utilized a mailed survey to all patients
      discharged from a university affiliated hospital with the diagnosis of ACS during
      a 3-year period. Perceived work performance was measured using the Work
      Performance Scale (WPS). Independent variables included health status (SF-8, PCS
      8, MCS-8 and EQ-5D visual analog scale), cardiac functional status (Duke activity
      status index), symptom count, comorbidity index, patient-perceived cardiac
      disease severity, medication count and compliance, job satisfaction, current
      employment duration, patient demographics and ACS type. Step-wise multivariate
      linear regression models determined the independent variables with significant
      association (p < 0.05) to WPS. Of 1,217 patients surveyed, 490 (40%) responded,
      including 158 currently working (study sample). The regression model with the
      highest explanatory ability (r(2) = 0.29) included number of symptoms, age,
      perceived cardiac severity and PCS-8, with more symptoms, higher perceived
      severity, higher age and lower PCS-8 scores associated with lower WPS. Currently
      employed ACS patients report a high level of work performance. Symptom burden,
      perceived disease severity, age and physical function appear to be associated
      with perceived work performance.

PMID- 16103669
TI  - Apolipoprotein E epsilon4 allele differentiates the clinical response to
      donepezil in Alzheimer's disease.
AB  - The existence of an association between apolipoprotein E (APOE) and Alzheimer's
      disease (AD) has been reported in several studies. The possession of an ApoE
      epsilon4 allele is now considered a genetic risk factor for sporadic AD. There
      has been a growing agreement about the role exerted by the ApoE epsilon4 allele
      on the neuropsychological profile and the rate of cognitive decline in AD
      patients. However, a more controversial issue remains about a possible influence
      of the APOE genotype on acetylcholinesterase inhibitor therapy response in AD
      patients. In order to address this issue, 81 patients diagnosed as having
      probable AD were evaluated by a complete neuropsychological test battery at the
      time of diagnosis (baseline) and after 12-16 months (retest). Patients were
      divided into two subgroups: (1) treated with donepezil at a dose of 5 mg once a
      day (n = 41) and (2) untreated (n = 40). Donepezil therapy was started after
      baseline evaluation. The APOE genotype was determined according to standardized
      procedures. We evaluated the possible effect of the APOE genotype on the
      neuropsychological tasks in relation to donepezil therapy. The statistical
      analysis of the results showed a global worsening of cognitive performances for
      all AD patients at the retest. Differences in the clinical outcome were analysed
      in the four subgroups of AD patients for each neuropsychological task. ApoE
      epsilon4 carriers/treated patients had improved or unchanged scores at retest
      evaluation for the following tasks: visual and verbal memory, visual attention
      and inductive reasoning and Mini Mental State Examination. These results indicate
      an effect of donepezil on specific cognitive domains (attention and memory) in
      the ApoE epsilon4 carriers with AD. This might suggest an early identification of
      AD patients carrying at least one epsilon4 allele as responders to donepezil
      therapy.

PMID- 16103670
TI  - Cognitive impairment is the major risk factor for development of geriatric
      syndromes during hospitalization: results from the GIFA study.
AB  - OBJECTIVE: To detect the main factors associated with the occurrence of specific
      geriatric syndromes (namely pressure sores, fecal incontinence, urinary
      incontinence and falls) in elderly patients during hospitalization. DESIGN:
      Observational prospective study. SETTING: Eighty-one community and university
      hospitals throughout Italy. PARTICIPANTS: 13,729 patients aged 65 years and more,
      consecutively admitted to medical or geriatric acute wards during 20 months in
      the period between 1991 and 1998. MEASUREMENTS: Occurrence of pressure sores,
      fecal incontinence, urinary incontinence and falls during the stay in hospital.
      RESULTS: Pressure sores were already present in 3% of hospitalized subjects,
      fecal incontinence in 7.3%, while urinary incontinence, evaluated on a subgroup
      of total population (4,268 subjects), had a prevalence of 22.3%. During
      hospitalization (mean stay of 15 days), 74 subjects developed new pressure sores,
      55 became fecal and 35 urinary incontinent, and 279 subjects had at least one
      episode of fall. In multivariate analyses, cognitive impairment, advanced age
      (85+ years), length of stay (more than 3 weeks) and severe disability were the
      main independent predictors of development of the four geriatric syndromes, with
      cognitive impairment as the most significant risk factor for all the four
      outcomes (OR 4.9, 95% CI 2.4-9.9 for pressure sores; OR 6.3, 95% CI 3.0-13.0 for
      fecal incontinence; OR 5.3, 95% CI 2.3-12.0 for urinary incontinence; OR 1.6, 95%
      CI 1.2-2.3 for falls). CONCLUSION: Very old people have a significant increased
      risk of several geriatric syndromes during the stay in hospital, particularly if
      it is long and they are cognitively impaired. A standardized comprehensive
      geriatric evaluation at admission could be helpful in detecting all subjects at
      risk and preventing the development of hospital-acquired geriatric syndromes.

PMID- 16103671
TI  - Rice gruel and rice starch reduce sorbitol-induced diarrhoea in cecectomized
      rats.
AB  - BACKGROUND/AIMS: Sorbitol (S), a widely used sugar substitute in sugar-free
      products, has shown intolerance manifested by abdominal pain, bloating and
      diarrhoea in children and adults. The nutritional and S-induced diarrhoea
      preventive effect of rice gruel (RG) and rice starch (RS) was studied in
      cecectomized rats. METHODS: During the 41-day experimental period, control, RG or
      RS, S, and S+RG or RS-containing diets were provided in four consecutive phases.
      The diet compositions were changed depending on the conditions of the diarrhoea.
      Faecal appearances of S- and S+RG/RS-fed groups were observed daily and scored
      (diarrhoea = 2, mixed fae ces = 1, normal faeces = 0) to evaluate the degree of
      diarrhoea. RESULTS: The diarrhoeal scores were significantly (p < 0.05) decreased
      in all phases of the RG- or RS-fed group compared to the control group (S). Serum
      lipid and colonic organic acid concentrations were decreased while faecal bile
      acids and neutral sterol concentrations were increased in the RG-fed group
      compared to the control which were measured in the samples collected from the
      last phase of the experiment. CONCLUSION: These results indicate that RG and RS
      may be useful additives in S-containing food products to prevent the possible
      risk of diarrhoea in humans.

PMID- 16103672
TI  - Multifactorial iron man.

PMID- 16103673
TI  - Iron stores modulate hepatic hepcidin expression by an HFE-independent pathway.
AB  - BACKGROUND/AIMS: In HFE-related hereditary hemochromatosis an inappropriately low
      hepatic expression of the iron-regulatory peptide hepcidin (encoded by HAMP) has
      been suggested to cause iron overload. The aim of the present study was to
      evaluate whether the hepatic expression of HAMP in relation to iron stores
      requires HFE or might involve other important iron-related genes including HJV
      (encoding hemojuvelin) and TFR2 (encoding transferrin receptor-2). METHODS: Using
      quantitative RT-PCR, the iron-dependent hepatic expression patterns of HAMP, HJV,
      and TFR2 were evaluated in human and murine HFE-related hemochromatosis. RESULTS:
      The overall level of hepatic HAMP expression in human and murine HFE-related
      hemochromatosis is impaired but can still be modulated by iron stores. Moreover,
      we demonstrate an HFE-independent correlation between the expression of HAMP and
      TFR2 in mouse and human livers. On the other hand, a strong correlation between
      the hepatic expression of HAMP and HJV was only found in hemochromatosis patients
      and Hfe-deficient mice. CONCLUSION: The central pathogenetic step in HFE-related
      hemochromatosis is an impaired basal expression of HAMP rather than a lack of
      HAMP upregulation in response to iron stores. An HFE-independent pathway that
      seems to involve TFR2 and HJV can regulate HAMP expression under conditions of
      iron overload.

PMID- 16103674
TI  - Quality control of colorectal surgery with an extensive complication registration
      system.
AB  - BACKGROUND/AIMS: Since 1996, a standard registration is used to obtain a clear
      understanding of the complications that occur after colorectal surgery. In our
      registration system the cause of a complication and the detrimental effect to the
      patient's health are coded. METHODS: The treatment of colorectal diseases was
      evaluated to analyze the quality of medical care. RESULTS: From 1996 to 2000, a
      total of 169 complications were documented in 108 of the 353 patients operated
      on. Leakage of the anastomosis occurred in 22 cases (6%) and wound infection
      occurred in 11 cases (3%). Most of the complications required no or little
      medical attention (n = 101, 59%). 51% of the complications could be attributed to
      the physical condition of the patient. Surgical complications were the cause in
      31% of the cases and management problems in 16% of the cases. CONCLUSION: A
      registration system provides good insight into the frequency and severity of the
      complications after colorectal surgery. Extensive registration is mandatory to
      provide reliable information, comparing the results year by year. This provides
      the basis for continuous improvement of medical protocols on the surgical ward.

PMID- 16103675
TI  - Obstructing colorectal carcinoma: outcome and risk factors for morbidity and
      mortality.
AB  - BACKGROUND/AIMS: Emergency surgery for colorectal cancer is widely thought to be
      associated with high morbidity and mortality. The aim of this study was to assess
      the operative results of patients who had emergency operations for obstructing
      colorectal cancer. Clinical factors that might influence the outcome were also
      evaluated. PATIENTS AND METHODS: This is a retrospective study including 83
      patients who underwent emergency operations for completely obstructing colorectal
      cancers from 1991 to 2002. Demographic, clinical, and pathological variables were
      examined. Their influence on major morbidity and mortality was assessed using
      univariate and multivariate analyses. RESULTS: The overall and major morbidity
      rate was 67.5 and 32.5%, respectively. Mortality was 10.8%. Univariate analysis
      showed that high ASA class and perioperative blood transfusion were significantly
      associated with major complication, whereas older age and high APACHE II were
      linked to mortality. Independent risk factors for major morbidity were
      perioperative blood transfusion and high ASA class. The only independent
      predictor of postoperative death was high APACHE II score. CONCLUSIONS: Emergency
      surgery for obstructing colorectal carcinoma carries a negative impact on
      outcome. Patients with risk factors should undergo safe and least risky
      procedures. Moreover, their presence might help in selecting patients for
      intensive treatment after surgery.

PMID- 16103676
TI  - Levetiracetam in the treatment of status epilepticus in adults: a study of 13
      episodes.
AB  - Treatment of status epilepticus (SE) has changed little over the last two
      decades, but the burden of this condition remains important. There is thus a need
      for alternative pharmacological therapies. Levetiracetam (LEV) has a wide
      spectrum of action and a favorable pharmacokinetic profile; however, little data
      exist regarding its use in SE. We identified patients with SE who received LEV,
      in a database comprising 127 SE episodes. Demographic, clinical and
      pharmacological data were analyzed, and compared to a control group consisting of
      2 subjects from the database for each LEV patient, matched for age and sex. We
      identified 13 SE episodes occurring in 12 patients (10% of the database).
      Demographic, etiologic and clinical characteristics and outcome did not differ
      between the groups. Daily LEV dose ranged between 1,000-6,000 mg. Three patients
      were probable responders (23%), 1 responded to the treatment but subsequently
      died (8%), 4 were non-responders (31%, 1 died), and 5 had an undetermined
      response (38%). LEV may represent a useful alternative in the treatment of SE,
      particularly if a parenteral form of administration becomes available; to better
      define its role in this setting, prospective studies are needed.

PMID- 16103677
TI  - Early observations on duchenne-meryon muscular dystrophy.

PMID- 16103678
TI  - Historical descriptions of multiple sclerosis.
AB  - Modern understanding of multiple sclerosis is firmly founded on the labours of
      many neuroscientists of the last two centuries. The cost of the disease to its
      victims is nowhere better displayed than in their personal accounts of their
      illnesses. Two figures stand out: the high-born aristocrat, Augustus D'Este and
      his diaries of the early 19th century and the courageous if histrionic Bruce
      Frederick Cummings in the early 20th century. This paper cannot do justice to
      their major contributions, but seeks to summarise them to give the flavour of
      their symptoms, disabilities and the way they were regarded by doctors and the
      people at large. The early medical studies of Carswell, Cruveilhier, Charcot and
      many others are briefly reviewed as relevant settings to these personal
      histories.

PMID- 16103679
TI  - Dystrophy, abiotrophy, amyotrophy.

PMID- 16103680
TI  - Transvaginal ultrasonography of the endometrium in postmenopausal Japanese women.
AB  - AIMS: To determine the cut-off level of endometrial thickness for detecting
      endometrial disease on a large scale of screening and to examine the usefulness
      of transvaginal ultrasonography (TVS) for endometrial disease screening in
      asymptomatic postmenopausal Japanese women. METHODS: The study involved 1,400
      postmenopausal women in whom endometrial thickness was measured with TVS, and
      then compared with the histopathological diagnosis of endometrial specimens.
      RESULTS: The prevalence of endometrial disease in asymptomatic and symptomatic
      cases was 2.3 and 21%. In symptomatic cases, at a cut-off limit of 3 mm for
      endometrial thickness, the sensitivity for detecting endometrial disease was 94%,
      specificity 70% and positive predictive value 46%. With an endometrial thickness
      < or = 3 mm, the probability that endometrial disease would be overlooked was
      0.025. In asymptomatic cases, the corresponding figures at a cut-off limit of 3
      mm were 90, 84, 12% and 0.003. CONCLUSIONS: TVS does not appear to be an
      effective screening method in asymptomatic postmenopausal Japanese women because
      of the low prevalence of endometrial disease in this population. We recommend a
      normal cut-off level for endometrial thickness of 4 mm in symptomatic
      postmenopausal Japanese women.

PMID- 16103681
TI  - Variability of the 3'APOB minisatellite locus in Eastern Slavonic populations.
AB  - OBJECTIVE: To describe and compare the 3' apolipoprotein (Apo) B minisatellite
      allele frequency distributions of Eastern Slavonic populations and their Uralic,
      Altaic, and Caucasian speaking neighbors. METHODS: Healthy individuals of 10
      populations among Russians, Byelorussians, Komis and Bashkirs were studied for
      variable number tandem repeats (VNTRs) in the 3'ApoB minisatellite region. Data
      were analyzed with other results reported for this polymorphism in eastern
      Europeans and Siberians. RESULTS: Allele frequency spectra in Eastern Slavonic,
      Northern Caucasian and Finno-Ugric speaking populations are bimodal with the main
      peak in alleles 34-36 and a secondary mode around allele 48, whereas Altaic
      speaking populations have a unimodal allele frequency distribution with a peak of
      around 34-36 VNTRs. Population relationships were revealed using both
      multidimensional scaling analysis (based on Nei's genetic distance estimate) and
      testing for genetic heterogeneity. Eastern Slavonic populations (Russians,
      Ukrainians, Byelorussians) were most closely related to each other and formed a
      separate tight clusterwhen plotted. Testing for genetic heterogeneity among the
      Eastern Slavonic ethnic groups revealed maximum diversity among Byelorussians,
      followed by Russians, then Ukrainians. The 3'ApoB minisatellite variability
      reveals little heterogeneityamong the Eastern Slavonic ethnic groups, whereas
      there wassignificant heterogeneity for Northern Caucasian and Altaic speakers.
      CONCLUSION: For this 3'ApoB polymorphism the Eastern Slavonic populations,
      despite their wide geographical distribution, appear to be much more homogenous
      than other ethnic groups of the region. Multidimensional scaling analysis of
      these data allowed for differentiation between individual populations from an
      ethnic group even if there is little heterogeneity.

PMID- 16103682
TI  - Final height in children with medulloblastoma treated with growth hormone.
AB  - BACKGROUND: Medulloblastoma is the most frequent primary solid central nervous
      system tumour in children. The 5-year survival rate is at present at about 60%.
      Height in general is severely compromised in survivors. The present study is an
      extension of the investigation by the author's group of the effect of exogenous
      growth hormone (GH) among medulloblastoma patients. METHODS: A total of 113
      patients with medulloblastoma (out of 682 cases documented in KIGS, Pfizer
      International Growth Database) were treated with GH till final height was
      achieved. At the start of GH therapy (median dose 0.18 mg/kg/week), patients were
      8.9 years old and had a median height SDS of -1.6. RESULTS: After 6.8 years of
      GH, final height SDS was -1.9, reflecting an overall loss in height of 0.3 SDS.
      This contrasted with an age-matched group of patients with idiopathic growth
      hormone deficiency (iGHD, n = 1,986), whose gain in height was 1.6 SDS on the
      same dose. The index of responsiveness averaged -0.9 during the first prepubertal
      year and -2.0 during total pubertal growth, thus indicating a major impairment in
      responsiveness to GH as compared to iGHD. Height at GH start, which correlated
      positively with the age at disease onset, was found to be the major determinant
      of final height. CONCLUSIONS: Our findings show that attempts to improve the
      height outcome in medulloblastoma must involve earlier recognition and treatment
      with higher-than-replacement doses of GH; additionally, modifications in cancer
      treatment programs need to be considered, such as lowering the dose of
      craniospinal irradiation or avoiding it as far as possible.

PMID- 16103683
TI  - Quality of life assessment of growth hormone deficiency in adults (QoL-AGHDA):
      comparison of normative reference data for the general population of England and
      Wales with results for adult hypopituitary patients with growth hormone
      deficiency.
AB  - BACKGROUND/AIM: Age- and gender-specific reference values for the quality of life
      (QoL) measures used in assessing the impact of growth hormone deficiency (GHD)
      are important. The objective of this study was to develop such data for the QoL
      AGHDA instrument for the population of England and Wales and to demonstrate the
      QoL deficit in patients with GHD. METHODS: For the purpose of this study, a
      questionnaire was developed that contained the EurQoL EQ-5D, QoL-AGHDA, questions
      recording an individual's general situation and social functioning, and a self
      reported five-point rating scale of general health. The questionnaire was mailed
      out to a sample of 1,190 individuals drawn from the general population of England
      and Wales. Corresponding data for 836 patients were retrieved from KIMS (Pfizer
      International Metabolic Database). The postal survey data were weighted to ensure
      that they were representative of the general population. RESULTS: The mean
      weighted QoL-AGHDA scores for the general population were 6.2 and 7.1 for men and
      women, respectively, compared with 13.6 and 15.7 for patients. For both males and
      females the differences in mean QoL-AGHDA scores between the general population
      and patients were statistically significant for all age categories (p < 0.01). In
      the general population the mean QoL-AGHDA score for each category of self
      assessed health status increased progressively, indicating a poorer QoL as health
      status declined. CONCLUSIONS: This study reports QoL-AGHDA normative values for
      the population of England and Wales and confirms the extent of QoL impairment in
      patients with GHD in comparison with the general population.

PMID- 16103684
TI  - Adrenocortical response to ovine corticotropin-releasing hormone in young men:
      cortisol measurement in matched samples of saliva and plasma.
AB  - BACKGROUND: Assessment of hypothalamic-pituitary-adrenal (HPA) axis function in
      stress-related health problems in humans is frequently carried out as a dynamic
      test by measuring the profile of increment in adrenocortical hormone (ACTH)
      and/or cortisol level in plasma in response to corticotropin-releasing hormone
      (CRH) administration. However, obtaining multiple blood samples for this type of
      test is not only an invasive procedure but also problematic to use in individuals
      with constricted or damaged veins which collapse during the blood draw such as
      the injecting drug users (IDUs) and HIV-1-infected individuals. Salivary cortisol
      measurement presents a non-invasive alternate approach to evaluate HPA axis
      activity in different situations. In order to validate the efficacy of salivary
      cortisol measurement for a dynamic test in IDUs and HIV-1-infected individuals,
      the present study was carried out to evaluate the cortisol profile in matched
      samples of plasma and saliva in healthy young men in response to ovine CRH (oCRH)
      administration. METHODS: Cortisol levels were measured in matched samples of
      plasma and saliva of healthy young men at baseline and over a 90-min period after
      administration of a single low dose of oCRH (1 microg/kg). RESULTS: Salivary
      cortisol levels were found to follow the profile similar to that of plasma,
      increasing significantly at each time point after oCRH administration from their
      respective baseline values (all Sign tests, p < 0.05). The peak level of cortisol
      occurred at 30 min in both fluids. Although salivary cortisol concentration was a
      fraction of the total plasma cortisol levels at all time points, there was a
      significant correlation in the values between the two fluids at baseline (r =
      0.87, p < 0.02) as well as at 90 min (r = 0.70, p < 0.03). CONCLUSION: The
      findings support the earlier studies and substantiate the efficacy of using
      salivary free cortisol measurement for assessment of dynamic function of
      pituitary-adrenal axis in healthy young men and its application in individuals
      such as IDUs and HIV-infected individuals who may have difficulty in donating
      multiple blood samples.

PMID- 16103685
TI  - Severe hyperinsulinaemic hypoglycaemia in a baby born to a mother taking oral
      ritodrine therapy for preterm labour.
AB  - Hyperinsulinism of infancy is a major cause of persistent hypoglycaemia in the
      newborn period. Transient mild self-limiting hyperinsulinaemia and hypoglycaemia
      have been described in neonates born to mothers taking ritodrine therapy for
      premature labour. Ritodrine crosses the placental barrier and enters the fetal
      circulation readily but the mechanism of how it causes hyperinsulinaemia and
      hypoglycaemia is unclear. We report the case of severe prolonged
      hyperinsulinaemic hypoglycamia in a neonate born to a mother taking ritodrine
      therapy from 16 weeks' gestation for preterm labour. The hyperinsulinaemic
      hypoglycaemia was managed with oral nifedipine as diazoxide was contraindicated
      due to fluid overload. Possible mechanisms of ritodrine-induced hypoglycaemia and
      insulin secretion are discussed.

PMID- 16103686
TI  - NOS 1 is required for allergen-induced expression of NOS 2 in mice.
AB  - BACKGROUND: Although increased nitric oxide (NO) production in asthma is mediated
      largely by upregulation of the inducible form of nitric oxide synthase (iNOS, or
      NOS 2), some studies have suggested an important role for the usually
      constitutive neural NOS isoform (nNOS, or NOS 1). AIM: To investigate how NOS 1
      may influence allergic inflammation, we used NOS 1 knockout mice and their wild
      type (WT) controls. METHODS: Mice were sensitized and challenged with ovalbumin
      (OVA) using a protocol known to upregulate NOS 2 in the airways. RESULTS: In
      addition to expected increases in NOS 2 activity, OVA challenge led to increases
      in calcium-dependent NOS activity, which was accounted for by increased
      expression of NOS 1 at both mRNA (n = 5, p < 0.001) and protein levels (n = 5, p
      < 0.01). In NOS-1-deficient mice, OVA challenge induced less eosinophilia (n = 7,
      p < 0.05) and much less NO production (n = 10, p < 0.01) than in WT controls,
      reflecting not only the expected absence of NOS 1, but also lack of upregulation
      of NOS 2. This interaction appeared to be stimulus specific as NOS-1-deficient
      mice did upregulate NOS 2 following exposure to lipopolysaccharide (n = 5, p <
      0.001). CONCLUSIONS: These findings underscore the importance of NOS 1 in
      allergic airway inflammation and suggest a mechanism by which NOS 1 may influence
      overall NO production in the airways.

PMID- 16103687
TI  - Characteristic features of allergic airway inflammation in a murine model of
      infantile asthma.
AB  - BACKGROUND: The pathophysiology of infantile asthma may differ from that in older
      children or in adults, partly because of the different immune response depending
      upon maturation. In adult mice, the sensitizing dose of antigen is known to be
      critical to the polarized development of helper T cell subsets and allergic
      airway inflammation. We wanted to know the characteristics of allergic airway
      inflammation of infantile asthma by developing a murine model. METHODS: BALB/C
      mice at different stages of maturation (juvenile: 3 days after birth; adult: 8
      weeks of age) were sensitized with 10 or 1,000 microg ovalbumin (OVA) or vehicle.
      The animals were then challenged with aerosolized OVA or saline once a day during
      6 consecutive days. After the final challenge, bronchial hyperresponsiveness
      (BHR), bronchoalveolar lavage fluid (BALF), histological changes in the airways
      and immunological status were examined. RESULTS: In both juvenile and adult
      animals, sensitization with 10 microg OVA induced the T helper 2 response
      (elevated IL-4 and decreased IFN-gamma levels). BHR, airway eosinophilia, the
      inflammatory cell infiltration, goblet cell metaplasia (GCM), and IgE antibody
      production were more prominent in animals given this dose than 1,000 microg OVA.
      Among these responses, GCM as well as BALF IL-4, and BHR were comparable between
      juvenile and adult animals, whereas other parameters were lower in juvenile
      animals, especially in those given 1,000 microg OVA. CONCLUSION: GCM and,
      consequently, airway mucus hypersecretion may be an important component of
      allergic airway inflammation in infantile asthma.

PMID- 16103688
TI  - Cytokine and antibody responses in birch-pollen-allergic patients treated with
      genetically modified derivatives of the major birch pollen allergen Bet v 1.
AB  - BACKGROUND: Recently, recombinant hypoallergenic derivatives of the major birch
      pollen allergen, Bet v 1, were used to treat birch-pollen-allergic patients in a
      double-blind, placebo-controlled, multi-centre immunotherapy study. The aim of
      this study was to evaluate the effects of vaccination with aluminium-hydroxide
      adsorbed recombinant Bet v 1 derivatives versus placebo on T-cell, cytokine and
      antibody responses in a subgroup of patients. METHODS: Blood was drawn from
      patients of the Swedish centre (n = 27; rBet v 1 fragments: n = 10; rBet v 1
      trimer: n = 8, and placebo-aluminium hydroxide: n = 9) before the start and after
      completion of the treatment. PBMC were stimulated with rBet v 1 and analysed for
      cytokine (IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-gamma)-secreting cells by
      ELISpot. Bet v 1-specific antibody levels in serum (IgG(1-4), IgE and IgA) were
      measured by ELISA. Skin prick tests with defined Bet v 1 concentrations were
      performed before and 10-11 months after the beginning of the study. RESULTS: Bet
      v 1-specific IgG levels, consisting of IgG(1), IgG(2) and IgG(4), were
      significantly increased after treatment with recombinant allergen derivatives.
      Treatment with rBet v 1 trimer led to a significant (p < 0.05) reduction of Bet v
      1-reactive IL-5- and IL-13-producing cells, reflecting a reduced Th2 response. In
      addition, a decreased number of Bet v 1-reactive IL-4 producing (p = 0.07) and an
      increase of IL-12-producing (p = 0.06) cells was noted in the trimer-treated
      patients. In contrast to placebo, active treatment resulted in significantly
      reduced immediate-type skin reactions to Bet v 1 even 10-11 months after
      treatment. CONCLUSION: Vaccination with recombinant hypoallergenic Bet v 1
      derivatives induces a Bet v 1-specific IgG response and leads to reduced skin
      reactivity in allergic patients. A reduction of Bet v 1-specific Th2 responses
      was observed in trimer-treated patients, which may reflect the intrinsic property
      of this allergen derivative.

PMID- 16103689
TI  - Expression of interleukin-16 in allergic rhinitis.
AB  - BACKGROUND: Interleukin-16 (IL-16) has been characterized as a chemoattractant
      for a variety of CD4+ T cells. Several inflammatory diseases, including allergic
      disorders, have been reported to correlate with IL-16. We first examined the IL
      16 expression of serum and mucosal tissue in patients with allergic rhinitis.
      METHODS: Forty-eight patients with a clinical history of house dust mite (HDM) or
      pollen-sensitive allergic rhinitis were included in this study. Serum IL-16 was
      analyzed by enzyme-linked immunosorbent assay (ELISA). IL-16 expression of nasal
      mucosa was detected by immunohistochemistry. RESULTS: IL-16 levels were elevated
      in the serum of patients with allergic rhinitis compared with normal controls. In
      particular, serum IL-16 levels in HDM-sensitive patients were higher than those
      in pollen-sensitive patients. IL-16 was significantly correlated with eosinophils
      in the peripheral blood of allergic rhinitis patients. Histologically, IL-16 was
      expressed in infiltrated lymphocytes and nasal gland cells. CONCLUSIONS: Our data
      indicate that one of the sources of elevated serum IL-16 in allergic patients may
      be gland cells and lymphocytes in allergic nasal mucosa. This IL-16 cytokine may
      be strongly associated with the developmental mechanism of allergic rhinitis.

PMID- 16103690
TI  - Seasonal rhinitis, clinical characteristics and risk factors for asthma.
AB  - BACKGROUND: The aim was to determine the clinical characteristics of patients
      with seasonal rhinitis (SR) and to disclose differences in the treatment of SR
      between an adult allergy clinic and other clinics over time. METHODS: A
      retrospective study was conducted based on clinical records of 774 out of 955
      patients diagnosed with SR in an adult allergy clinic between 1 January 1991 and
      31 December 2003. RESULTS: The mean age of the patients was 29.1 +/- 9.29 years
      and 62.7% were female. The most common major complaints of the patients were
      nasal symptoms in 82.3%. The mean duration of the disease was 6.76 +/- 6.8 years.
      The patients were symptomatic with a mean of 3.5 +/- 1.7 months a year, mostly
      during the period between April and July. Skin prick tests were positive in 685
      patients (90.3%), where the most common sensitivity was against timothy grass
      (85.1%). The most common accompanying allergic diseases were food
      hypersensitivity in 14%, bronchial asthma in 13.4%, and drug allergy and/or
      intolerance in 9.6%. Although the use of specific immunotherapy and short-acting
      sedative antihistamines decreased over time, the use of nasal steroids and long
      acting nonsedative antihistamines tended to increase before admission to our
      clinic. Older age (OR: 1.77, 95% CI: 1.06-2.94), presence of familial atopy (OR:
      1.72, 95% CI: 1.04-2.85), respiratory symptoms (OR: 2.10, 95% CI: 1.75-2.50),
      ocular symptoms (OR: 0.77, 95% CI: 0.61-0.98) and metal allergy (OR: 0.25, 95%
      CI: 0.07-0.89) were associated with the development of asthma in patients with
      SR. CONCLUSION: SR lasts approximately 3.5 months and the main cause in Ankara,
      Turkey is grass pollen sensitivity. Patients with any other allergic conditions
      make up 39.8% of the patients. SR patients are referred to allergy clinics quite
      late, which might be due to SR not being considered as a serious disease.

PMID- 16103691
TI  - Endogenous cannabinoid receptor agonists inhibit neurogenic inflammations in
      guinea pig airways.
AB  - BACKGROUND: Although neurogenic inflammation via the activation of C fibers in
      the airway must have an important role in the pathogenesis of asthma, their
      regulatory mechanism remains uncertain. OBJECTIVE: The pharmacological profiles
      of endogenous cannabinoid receptor agonists on the activation of C fibers in
      airway tissues were investigated and the mechanisms how cannabinoids regulate
      airway inflammatory reactions were clarified. METHODS: The effects of endogenous
      cannabinoid receptor agonists on electrical field stimulation-induced bronchial
      smooth muscle contraction, capsaicin-induced bronchoconstriction and capsaicin
      induced substance P release in guinea pig airway tissues were investigated. The
      influences of cannabinoid receptor antagonists and K+ channel blockers to the
      effects of cannabinoid receptor agonists on these respiratory reactions were
      examined. RESULTS: Both endogenous cannabinoid receptor agonists, anandamide and
      palmitoylethanolamide, inhibited electrical field stimulation-induced guinea pig
      bronchial smooth muscle contraction, but not neurokinin A-induced contraction. A
      cannabinoid CB2 antagonist, SR 144528, reduced the inhibitory effect of
      endogenous agonists, but not a cannabinoid CB1 antagonist, SR 141716A. Inhibitory
      effects of agonists were also reduced by the pretreatment of large conductance
      Ca2+ -activated K+ channel (maxi-K+ channel) blockers, iberiotoxin and
      charybdotoxin, but not by other K+ channel blockers, dendrotoxin or
      glibenclamide. Anandamide and palmitoylethanolamide blocked the capsaicin-induced
      release of substance P-like immunoreactivity from guinea pig airway tissues.
      Additionally, intravenous injection of palmitoylethanolamide dose-dependently
      inhibited capsaicin-induced guinea pig bronchoconstriction, but not neurokinin A
      induced reaction. However, anandamide did not reduce capsaicin-induced guinea pig
      bronchoconstriction. CONCLUSIONS: These findings suggest that endogenous
      cannabinoid receptor agonists inhibit the activation of C fibers via cannabinoid
      CB2 receptors and maxi-K+ channels in guinea pig airways.

PMID- 16103692
TI  - Angiotensin II stimulates matrix metalloproteinase secretion in human vascular
      smooth muscle cells via nuclear factor-kappaB and activator protein 1 in a redox
      sensitive manner.
AB  - The renin-angiotensin system contributes to atherogenesis. Matrix
      metalloproteinases (MMP) are thought to participate in plaque destabilization
      through degradation of extracellular matrix. This study tested whether
      angiotensin II (ANG II) induces MMP in human vascular smooth muscle cells (SMC).
      ANG II induced expression of MMP-1, -3, and -9, but not of MMP-2 in SMC. The
      expression of MMP-1, a key enzyme for collagen degradation, was studied in
      detail. SMC stimulated with ANG II concentration-dependently released
      enzymatically active MMP-1. The ANG II type 1 receptor antagonists losartan and
      candesartan blocked ANG-II-induced MMP-1 release. Inhibition experiments with
      actinomycin D suggest ANG-II-induced MMP-1 mRNA regulation at the transcriptional
      level. Decoy oligodeoxynucleotides against nuclear factor-kappaB and activator
      protein 1 inhibited MMP-1 secretion, demonstrating participation of these
      transcription factors in MMP-1 transcription. Stimulation of MMP-1 by ANG II
      depended on cyclooxygenase 2. The antioxidants pyrrolidine dithiocarbamate and N
      acetylcysteine, the flavin protein inhibitor diphenylene iodonium, and the
      NADP(H) oxidase inhibitor apocynin blocked MMP-1 release, suggesting a redox
      sensitive mechanism involving NADP(H) oxidase. The reactive oxygen species (ROS)
      donor 2,3-dimethoxy-1,4-naphthoquinone induced MMP-1 secretion and enhanced ANG
      II-stimulated MMP-1 expression. These findings indicate that ROS may increase
      their own production by activation of NADP(H) oxidase. The capability of ANG II
      to induce functionally active MMP in human SMC may contribute to the altered
      plaque composition seen in complicated stages of atherosclerosis.

PMID- 16103693
TI  - Retinopathy in newly diagnosed type 2 diabetes mellitus.
AB  - OBJECTIVE: To study the prevalence of diabetic retinopathy and its association
      with risk factors in newly diagnosed type 2 diabetic patients in two primary care
      diabetic clinics in Kuwait. SUBJECTS AND METHODS: All newly diagnosed type 2
      diabetes mellitus patients attending Ferdous and Yarmouk Health Care Diabetic
      Clinics in Farwaniya and Asma Health Areas, respectively, during the period of
      January 2002 to July 2004 were examined for the presence of diabetic retinopathy
      by color fundus photographs. Risk factors such as sex, age, hypertension,
      nephropathy, hyperglycemia, level of glycated hemoglobin, microalbuminuria and
      hyperlipidemia were evaluated by statistical analysis for their possible
      association with the presence of diabetic retinopathy at the time of diagnosis of
      diabetes. RESULTS: Of the 92 newly diagnosed type 2 diabetes mellitus patients
      studied, diabetic retinopathy was present in 7 (7.6%) patients. Two of the 7
      patients had maculopathy that needed treatment by photocoagulation. High glycated
      hemoglobin in 51 patients (55.4%), microalbuminuria in 25 (27.2%), hypertension
      in 29 (315%), hyperlipidemia in 69 (75%), obesity in 45 (48.9%) and overweight in
      37(40.2%) were noted in the study population. Microalbuminuria was weakly
      associated with the presence of retinopathy (p = 0.08) at the time of diagnosis
      of diabetes mellitus, but other risk factors were not statistically significant.
      CONCLUSIONS: Prevalence of diabetic retinopathy was 7.6% among the study
      population. Maculopathy was present in 2 of the 7 patients needing
      photocoagulation.

PMID- 16103694
TI  - Genetic predisposition to 4NQO-induced tongue carcinogenesis in the rat.
AB  - OBJECTIVE: This study aims to elucidate the genetic basis of predisposition to 4
      nitroquinoline 1-oxide (4NQO)-induced tongue cancers (TCs). MATERIALS AND
      METHODS: We have reported that inbred Dark-Agouti (DA) strain rats were highly
      susceptible to 4NQO-induced TCs, whereas Wistar/Furth (WF) rats were resistant to
      tongue squamous cell carcinomas induced by oral administration of 4NQO. Using
      size and number of the tumours as quantitative parameters, responsible host loci
      were analysed by an interval mapping of F2 intercross of DA and WF given
      carcinogenic regimen. Also, loss of heterozygosity (LOH) at these loci was
      analysed in tongue cancers in (DA x WF) F1. RESULTS: We identified and mapped 5
      significant quantitative trait loci (QTL), the Tongue squamous cell carcinoma 1-5
      (Tscc1-5), and several other suggestive QTL that determine susceptibility to 4NQO
      induced TC. Study of TCs induced in (DA x WF)F1 rats revealed a high frequency of
      LOH in the chromosomal regions of Tscc2, 3, and 4 and also of suggestive QTL on
      chromosomes 5 and 6. The fact that LOH was found only in larger TCs indicates
      that LOH occurred in the process of tumour progression. In most LOH, the allele
      of the resistant WF strain was lost, suggesting that these loci may encode tumour
      suppressor genes. In larger TCs, in addition to LOH, point mutations and the
      methylation of possible candidate genes were accumulated. CONCLUSION: These
      observations indicate that the 4NQO-induced TC in the rat is a multifactorial
      disease of a polygenic trait. This model will be useful to understand the
      complicated genetic basis of predisposition to oral cancers.

PMID- 16103695
TI  - Demographic pattern and clinical characteristics of patients with smear- positive
      pulmonary tuberculosis in kuwait.
AB  - OBJECTIVE: The aim of this study was to document various clinical factors that
      are likely to be of help in the control of tuberculosis in Kuwait. SUBJECTS AND
      METHODS: Details of patients with sputum positive for acid-fast bacilli in the
      period from January 1998 to December 2000 were collected retrospectively from the
      case records and population statistics from government sources. The data were
      then tabulated and analyzed. RESULTS: Of the 526 cases, 83.5% were expatriates
      and 16.5% Kuwaiti; 373 (70.9%) were male. Of the expatriates, 66.7% were from
      Asia and the Far East, 5.7% were > or =60 years. The annual incidence was 8.34
      per 100,000 population. The lowest incidence was observed in the Jahrah
      governorate with an overall incidence of 5 (2.0 among Kuwaitis and 6.4 among
      expatriates) per 100,000 population. The highest incidence overall (10.2) and
      among Kuwaitis (4.1) was observed in the Farwaniya governorate, while the highest
      incidence among expatriates was seen in the Capital governorate (13.4).
      Radiologically, 94 (19.5%) had minimal, 246 (51.5%) had moderately advanced and
      141 (29.3%) far-advanced disease. The majority of the patients (72%) had only +
      status for AFB in the smear. Hypercalcemia (25.7%), hyponatremia (22.15%) and
      hyperglycemia (29.9%) were common in the patients. Mean serum albumin was low
      (28.7 +/- 5.5 g/l). Two hundred and forty-seven (47.2%) were declared cured while
      116 (22.2%) completed treatment. Comparison between nationals and expatriates
      showed a significant difference only for age, smoking status, defaulter rate and
      place of residence. CONCLUSION: The lowest regional incidence was found in the
      Jahrah governorate. Both biochemical abnormalities and radiologically advanced
      presentations were common. Disease pattern and response to treatment was purely
      individual and did not differ with respect to nationality or race.

PMID- 16103696
TI  - Compliance and efficacy of hand rubbing during in-hospital practice.
AB  - OBJECTIVE: To compare alcohol-based hand rubbing with hand washing using
      antimicrobial soap regarding antimicrobial efficacy and compliance with routine
      practice in hospital and intensive care units. SUBJECTS AND METHODS: From
      February to June 2003, 35 nurses were randomly selected from a nursing staff of
      141 and divided into two groups: hand rubbing and hand washing groups. Hand
      cultures were obtained before and after health care procedures. The nurses were
      observed on days 1, 7 and 14 of the study, in order to determine compliance and
      efficacy of the hand hygiene methods. RESULTS: A total of 368 routine patient
      care activities were observed during the study period. Hand rubbing with alcohol
      based solutions significantly reduced the bacterial contamination of the hands of
      the nurses more than hand washing with an antimicrobial soap (54 and 27%,
      respectively; p < 0.01). Compliance was also better in the hand rubbing group
      than in the hand washing group (72.5 and 15.4%, respectively; p < 0.001).
      Compliance with hand rubbing was markedly lower among the nurses who had
      experience of more than 3 years in hospital practice. Both hand rubbing and hand
      washing compliance were poorer among nurses working in intensive care units than
      among nurses working in the other hospital wards. Generally, after taking off
      gloves, nurses preferred hand washing to hand rubbing. CONCLUSION: These data
      indicate that alcohol-based hand rubbing reduces mean bacterial counts on the
      hands of nurses more effectively than hand washing with antimicrobial soaps, and
      compliance rates with hand rubbing were also higher than with hand washing.
      Nevertheless, the compliance with hand rubbing was markedly lower in more
      experienced nurses.

PMID- 16103697
TI  - Surgical treatment for ipsilateral fractures of femoral neck and shaft.
AB  - OBJECTIVES: To review the primary and the final results of surgical management of
      ipsilateral femoral neck and shaft fractures. SUBJECTS AND METHODS: Seventeen
      patients (2 female, 15 male, average age 37 years, range 20-60) with ipsilateral
      femoral neck and shaft fractures were treated by compression plate fixation for
      the femoral shaft fractures and dynamic hip screw or cannulated cancellous screw
      fixation for the neck fractures in Al-Razi and Al-Jahra Hospitals, Kuwait, from
      March 1996 to June 2002. The clinical and radiological primary and final results
      were analyzed retrospectively. RESULTS: The average follow-up for the primary
      outcomes was 3.6 years (range 2-6 years). 100% union of the femoral neck
      fractures, 0% osteonecrosis of the femoral head and 77% union of the shaft
      fractures were achieved. Complications of femoral shaft fractures, nonunion and
      metal failure, occurred in 4 (23%) patients and postsurgical infection occurred
      in 1 patient. At the final follow-up, 15 (88%) patients achieved good clinical
      outcome and 2 (12%) had fair outcome. CONCLUSION: Our results show that
      compression plate fixation for the femoral shaft fracture and dynamic hip screw
      or cannulated screw fixation for the neck fracture in combination injury is a
      reliable and adequate technique.

PMID- 16103698
TI  - Prevalence of extended-spectrum beta-lactamases in Enterobacteriaceae,
      Pseudomonas and Stenotrophomonas as determined by the VITEK 2 and E test systems
      in a Kuwait teaching hospital.
AB  - OBJECTIVE: To determine the prevalence of extended-spectrum beta-lactamase (ESBL)
      producing members of the Enterobacteriaceae using VITEK 2 and E test systems.
      MATERIALS AND METHODS: A total of 3,592 consecutive gram-negative isolates
      (single isolate per patient) of the family of Enterobacteriaceae and Pseudomonas
      adjudged to be clinically relevant to the patient's infection were studied for
      ESBL production over a period of 1 year at Mubarak Al-Kabeer Hospital, Kuwait.
      Two methods were used: the automated VITEK 2 system and E test ESBL, a manually
      manipulated plastic strip containing various gradients of beta-lactam
      antibiotics. These tests and interpretative criteria for the results were
      performed according to the manufacturer's instructions. RESULTS: Of the 3,592
      bacterial isolates, 264 (7.5%) and 185 (5.2%) were positive for ESBL production
      by the VITEK 2 and E test, respectively. All the ESBL-producing Pseudomonas
      aeruginosa identified by VITEK 2 gave indeterminate results by E test. Prevalent
      ESBL producers, identified by the VITEK 2 versus E test, respectively, were:
      Citrobacter spp. (15 vs. 3.2%), K. pneumoniae (12.2 vs. 11.4%), Enterobacter spp.
      (12 vs. 3%), E. coli (6.5 vs. 5.6%), P. aeruginosa (6.5 vs. 0%) and Morganella
      spp. (2 vs. 1%). The most common infection associated with ESBL-producing
      pathogens was urinary tract infection (68.2%), followed by wound infection
      (14.4%) and bloodstream infection (6.1%). CONCLUSION: The result of this study
      showed a relatively high prevalence of clinically significant ESBL producers
      among the Enterobacteriaceae and Pseudomonas spp. at our teaching hospital. The
      VITEK 2 identified a higher prevalence of ESBL strains than the E test.

PMID- 16103699
TI  - Antimalarial prescribing practices: a challenge to malaria control in Ghana.
AB  - OBJECTIVE: The study was conducted to determine antimalarial prescribing
      practices among prescribers in 2 of the 6 sentinel sites established to document
      antimalarial drug efficacy in Ghana in order to provide some explanation
      underlying chloroquine treatment failures in the country. SUBJECTS AND METHODS:
      The study was descriptive combining both qualitative and quantitative designs.
      The qualitative design involved in-depth interviews of general prescribers in the
      Wassa West and Kassena Nankana districts using an interview guide. The
      quantitative design involved a review of Outpatient Department prescriptions of
      100 patients clinically diagnosed as having malaria within the year 2000 in each
      of the 7 selected health care facilities. RESULTS: The overall number of drugs
      prescribed per patient encounter was 4.3 in the Wassa West district and 3.0 in
      the Kassena Nankana district. The number of drugs per patient encounter was 5.4
      and 3.7 in private and government health care facilities, respectively. The
      commonly prescribed antimalarial drug in all the health care facilities visited
      was chloroquine. However, only 9.8% of prescriptions in private health care
      facilities contained correct doses of chloroquine compared to 54% in government
      health care facilities (p = 0.000). Prescriptions containing chloroquine
      injections were least likely to have correct doses of chloroquine. CONCLUSION:
      The findings indicate that although chloroquine remained the first-line drug in
      the treatment of uncomplicated malaria in the two districts, the level of
      appropriateness of doses prescribed was generally low. Inappropriate doses of
      chloroquine prescribed were more prevalent in private than government health care
      facilities, and among prescriptions containing injections.

PMID- 16103700
TI  - Comparison of antimicrobial resistance of Acinetobacter baumannii clinical
      isolates from Shanghai and Hong Kong.
AB  - OBJECTIVE: To compare the antimicrobial resistance patterns of Acinetobacter
      baumannii isolates from Shanghai and Hong Kong. MATERIALS AND METHODS: A total of
      212 A. baumannii strains of one isolate per patient were collected from Shanghai
      and Hong Kong from August 2002 to August 2003 that were tested against 15
      commonly used antimicrobial agents by the agar dilution method according to the
      NCCLS guidelines. RESULTS: Most beta-lactams showed no significant increase in
      activity after adding beta-lactamase inhibitors. The resistance rates of the
      isolates against ticarcillin-clavulanate, piperacillin-tazobactam and ampicillin
      sulbactam were for Shanghai 74.9, 70.9, 69.1% and Hong Kong 24.3, 18.9, 13.5%,
      respectively. Only cefoperazone-sulbactam showed a significant increase in
      activity against both Shanghai and Hong Kong strains, as the resistance rates
      dropped from 93.7 to 8.6% and 83.8 to 5.4%, respectively. The resistance rates of
      ceftazidime, cefepime, and gentamicin against Shanghai strains were 69.7, 72.0,
      73.7% and Hong Kong strains 69.7, 29.7, 18.9%, respectively. About 65% of
      Shanghai strains were found to be amikacin-resistant, however, all Hong Kong
      strains were sensitive. Fluoroquinolones including ciprofloxacin and levofloxacin
      had resistance rates over 60% against Shanghai strains, but only 13.5% against
      Hong Kong strains. Shanghai strains had imipenem and meropenem resistance rate of
      6.3%. Though 10.8% Hong Kong strains were resistant to meropenem, only 2.7% of
      them were resistant to imipenem. CONCLUSION: A. baumannii isolated from Shanghai
      were more resistant to all drugs except meropenem than Hong Kong isolates. The
      results indicate a need for measures to control the abuse of antibiotic usage in
      order to prevent the emergence of more multidrug-resistant isolates in both
      cities.

PMID- 16103701
TI  - Reference intervals for important serum sex steroid hormones, prostate-specific
      antigen, insulin-like growth factor-1 and IGF binding protein-3 concentration in
      a normal Kuwaiti adult male population.
AB  - OBJECTIVES: The purpose of this study was to determine the age-specific reference
      ranges for some important male sex steroid hormones, prostate-specific antigen
      (PSA), insulin-like growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3),
      for the Kuwaiti population. SUBJECTS AND METHODS: Blood samples were taken from
      398 consenting, fasting, healthy Kuwaiti males aged 15-80 years between 8.00 a.m.
      and 12.00 noon. The serum concentrations of total testosterone (TT), dehydro
      epiandrosterone sulfate (DHEAS), androstenedione (ADT), sex hormone binding
      globulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH),
      prolactin, PSA, IGF-1 and IGFBP-3 were determined. A distribution curve was
      plotted and age-specific reference levels were determined for each analyte. The
      reference interval for parameters with a normal distribution (Gaussian) was mean
      +/- 2 SD, while for the non-normal distribution (non-Gaussian), it was 2.5-97.5
      percentile. The reference intervals for the analytes obtained from this study
      were compared with those suggested by the kit manufacturers and currently used by
      the Ministry of Health, Kuwait Laboratories (MOHKL). RESULTS: Serum IGFBP-3 and
      ADT had normal distribution while other analytes had non-normal distribution. The
      reference intervals from this study, manufacturers kit and MOHKL were as follows:
      TT 3-31, 9-60, 8-35 nmol/l; DHEAS 0.9-11, 1.0-7.3, 2.2- 15.2 micromol/l; ADT 0.5
      4.3, 0.8-2.8, 2.0-9.2 nmol/l; LH 1-11, 0.8-7.6, 0.4-5.7 mIU/l; FSH 0.5-11, 0.7
      11.1, 1.1-13.5 mIU/l; prolactin 42-397, 53-360, 80-230 nmol/l; IGF-1 41-542, 78
      956, 71-261 ng/ml; IGFBP-3 88- 2,090, 900-4,000, 900-4,000 ng/ml, and PSA 0-3.1,
      0-4, 0-4 ng/ml, respectively. CONCLUSION: These data indicate that for Kuwaitis
      lower reference ranges must be used for serum TT, DHEAS, ADT, IGFBP-3 and PSA.
      There is no need to change the currently used reference interval for FSH whereas
      higher values must be used for LH, prolactin, and IGF-1.

PMID- 16103702
TI  - Multi-minicore disease: a report of 5 patients from Kuwait.
AB  - OBJECTIVE: To describe the characteristic clinical features and the diagnostic
      findings in muscle histochemistry of multi-minicore disease in 5 children from
      two unrelated families in Kuwait. CLINICAL PRESENTATION: The 5 children who
      presented with muscle weakness, 2 siblings from family 1 and the remaining 3 from
      the other (family 2), represent the classical type of multi-minicore disease;
      however, the two families differ in the course of the disease. Family 1 had the
      non-progressive form while family 2 had progressive weakness with respiratory
      complications and scoliosis. The diagnosis was confirmed in the index patients by
      muscle histochemistry, which demonstrated the typical minicores, which are devoid
      of oxidative enzyme activity. CONCLUSION: Both families represent the classical
      form, however, clinical variability in the course of the illness was demonstrated
      in these two families.

PMID- 16103703
TI  - Hemangioendothelioma of the spinal cord with intramedullary extension.
AB  - OBJECTIVE: Hemangioendotheliomas (HE) are vascular neoplasms that rarely involve
      the neuraxis. We report a rare case in the literature of intradural HE of the
      spinal cord with intramedullary extension. CLINICAL PRESENTATION AND
      INTERVENTIONS: A 41-year-old gentleman presented with low back pain, numbness and
      urinary retention. Imaging revealed a spinal tumor causing complete blockage at
      the level of T12. The tumor was resected and postoperative radiotherapy was
      delivered for residual disease. No disease was seen on MRI after 48 months of
      clinical and radiological follow-up. CONCLUSION: Complete excision of HE is the
      treatment of choice. Radiotherapy may play a role in the management of this
      lesion.

PMID- 16103704
TI  - Presacral extramedullary hematopoiesis: a diagnostic confusion concerning a rare
      presentation.
AB  - OBJECTIVE: To report a rare case of extramedullary hematopoiesis (EMH) with an
      asymptomatic intrapelvic mass in a patient with thalassemia major. CLINICAL
      PRESENTATION: The patient presented with a pelvic mass discovered by
      ultrasonography before undertaking laparoscopic cholecystectomy for gallstones.
      Technetium-99m MDP bone scan failed to differentiate EMH from malignancy. A fine
      needle aspiration smear was misdiagnosed when atypical megakaryocytes were
      interpreted as malignant cells. EMH was suggested by magnetic resonance imaging
      and confirmed by an ultrasound-guided Tru-Cut biopsy. CONCLUSION: This case
      report illustrates the need to consider EMH in the differential diagnosis of
      patients with chronic hematological disorders and mass lesions in extramedullary
      sites.

PMID- 16103705
TI  - Therapeutic drug monitoring of high-dose gentamicin in an elderly patient: a case
      report.
AB  - OBJECTIVE: To report the pharmacokinetics of gentamicin using traditional
      multiple daily doses and a high-dose regimen in an elderly patient. CLINICAL
      PRESENTATION AND INTERVENTION: An 80-year-old male who presented with mild renal
      failure received two different gentamicin dosing regimens, 60 mg every 8 h for
      septicemia and a high dose of 400 mg with extended interval for suspected
      endocarditis. Based on population parameters of k(e) (0.1030 h(-1)) and Vd (18.1
      liters), the initial gentamicin dosage regimen was calculated to be 80 mg every
      12 h. The measured peak and trough concentrations were used to calculate the
      individual parameters of k(e) (0.0749 h(-1)) and Vd (30.9 liters). After a 5
      mg.kg(-1) gentamicin dose, the Hartford nomogram was used to estimate the
      extended dosage interval. CONCLUSION: The Hartford nomogram may be a valid tool
      for estimating the dosage interval after a 5-mg.kg(-1) single dose of gentamicin.

PMID- 16103706
TI  - Leukocytoclastic vasculitis: a rare manifestation of propylthiouracil
      hypersensitivity.
AB  - OBJECTIVE: We report a case of leukocytoclastic vasculitis as a manifestation of
      propylthiouracil hypersensitivity. CLINICAL PRESENTATION AND INTERVENTION: A 66
      year-old woman with a history of a toxic adenoma was referred for evaluation of a
      purpuric rash on the legs and buttocks bilaterally. She was biochemically
      hyperthyroid. Biopsy of the skin lesions revealed leukocytoclastic vasculitis.
      Propylthiouracil therapy was discontinued, and methimazole started. The purpuric
      rash resolved and surgical treatment for toxic adenoma resulted in euthyroid
      state. CONCLUSION: This report indicated that leukocytoclastic vasculitis should
      be considered in the differential diagnosis of patients with a vasculitic rash.
      The discontinuation of the propylthiouracil was associated with disappearance of
      the lesions.

PMID- 16103707
TI  - Proceedings and abstracts of the International Conference on Applications of
      Molecular Biology in Modern Medicine. Kuwait, March 7-11, 2004.

PMID- 16103708
TI  - Megaloblastosis: from morphos to molecules.
AB  - OBJECTIVE: Megaloblastosis (i.e., megaloblastic transformation of erythroid
      precursor cells in the bone marrow) is the cytomorphological hallmark of
      megaloblastic anemia resulting from vitamin B12 and folate deficiency. It is
      characterized by a finely stippled lacy pattern of nuclear chromatin, which is
      believed to be an expression of deranged cellular DNA synthesis. However, the
      molecular basis of these cytomorphological aberrations still remains obscure. The
      current presentation describes the results of our studies on some molecular
      events associated with the development of megaloblastosis. METHODS: Transmission
      electron microscopy was used to study megaloblasts as well as DNA fibers
      extracted from megaloblastic and normoblastic bone marrows with and without
      treatment with proteinase K during the extraction procedure; cellular DNA
      synthesis in bone marrow cultures was studied by incorporation of 3H-thymidine
      and deoxyuridine suppression test, while histone biosynthesis in bone marrow
      cells was studied by in vitro incorporation of 3H-tryptophan, 3H-lysine and 3H
      arginine into histones. RESULTS: Derangement of DNA synthesis occurred due to an
      impaired de novo pathway of thymidylate synthesis in both vitamin-B12- and folate
      deficient human megaloblastic bone marrows as well as in the bone marrows of
      rhesus monkeys and rats with experimentally induced folate deficiency.
      Interestingly, folate-deficient monkeys developed frank megaloblastic bone
      marrows, but folate-deficient rats did not. On the other hand, megaloblastic
      changes in the bone marrow of human patients with myelodysplastic syndrome and
      erythroleukemia were not associated with this DNA synthetic abnormality.
      Biosynthesis of predominantly arginine-rich histones in megaloblastic bone
      marrows was markedly reduced as compared to normoblastic bone marrows, which was
      consistently associated with elongation and despiralization of chromosomes and
      finely stippled nuclear chromatin in megaloblasts. CONCLUSION: The impaired
      biosynthesis of predominantly arginine-rich nuclear histones appeared to be a
      common molecular event (a denominator) underlying the development of
      megaloblastosis with or without abnormal DNA synthesis.

PMID- 16103709
TI  - Sickle cell disease: a multigenic perspective of a single-gene disorder.
AB  - Although significant progress has been made in our understanding of sickle cell
      disease (SCD) and in the development of new therapies, many questions are still
      unanswered, and a cure remains elusive. This is particularly evident in the
      clinical heterogeneity of the disease. Studies have shown the importance of high
      hemoglobin F determinants and alpha-thalassemia as modifiers of disease severity,
      but these alone do not explain the diversity that is seen. This paper focuses on
      recent advances on the effect of nonglobin genetic modifiers on the SCD
      phenotype. The roles of polymorphic variants of (1) methylenetetrahydrofolate
      reductase gene in the pathogenesis of avascular necrosis, (2) factor V R485K and
      risk of venous thrombosis, and (3) UDP glucuronosyltransferase-1 polymorphism on
      serum bilirubin levels in SCD are discussed. Mention is made of genetic
      polymorphisms that might predispose to stroke. The application of gene expression
      profiling to the study of SCD is very promising and some preliminary data are
      provided.

PMID- 16103710
TI  - Molecular techniques in the diagnosis and management of infectious diseases: do
      they have a role in bacteriology?
AB  - The diagnosis and management of bacterial diseases has been done by traditional
      methods for a century or more. With the advent of molecular methods, however,
      these traditional approaches are being challenged. This review examines the pros
      and cons of traditional versus modern methods and tries to answer the question:
      when are molecular methods useful or essential? The following topics are
      addressed with appropriate examples: diagnosis; identification, typing and
      fingerprinting; pathogenesis; patient management; susceptibility to disease, and
      resistance to antimicrobial agents. It was concluded that there is still a place
      for both traditional and modern molecular methods, and training of staff must
      include both methodologies. Innovation is encouraged--but new technologies must
      be thoroughly tested before introduction into the routine lab. Liaison between
      laboratory scientist and physician is important, but above all experience is
      paramount.

PMID- 16103711
TI  - Mycobacterial gene cloning and expression, comparative genomics, bioinformatics
      and proteomics in relation to the development of new vaccines and diagnostic
      reagents.
AB  - Recent advances in molecular and genomic techniques have facilitated research on
      several aspects of mycobacteriology, such as diagnosis and the identification of
      new vaccines and therapeutic targets for various diseases, including
      tuberculosis. The aim of this review was to analyze the implications of advances
      in molecular and genomic techniques on the development of new vaccines for
      tuberculosis as well as immunological reagents to diagnose the disease. Gene
      cloning and expression, DNA and protein sequencing, polymerase chain reaction,
      comparative genomics, bioinformatics, proteomics and DNA and peptide synthesis
      coupled with the application of cellular immunology techniques have led to the
      identification of several antigens of Mycobacterium tuberculosis, which have
      potential for diagnosis and vaccine applications. For example, cross-reactive
      mycobacterial antigens like heat shock proteins, MTB32 and MTB39, have been
      identified as new vaccine candidates, and antigens encoded by M. tuberculosis
      specific genomic regions as new reagents for diagnosis.

PMID- 16103712
TI  - Mechanisms of drug resistance in cancer chemotherapy.
AB  - The management of cancer involves procedures, which include surgery, radiotherapy
      and chemotherapy. Development of chemoresistance is a persistent problem during
      the treatment of local and disseminated disease. A plethora of cytotoxic drugs
      that selectively, but not exclusively, target actively proliferating cells
      include such diverse groups as DNA alkylating agents, antimetabolites,
      intercalating agents and mitotic inhibitors. Resistance constitutes a lack of
      response to drug-induced tumour growth inhibition; it may be inherent in a
      subpopulation of heterogeneous cancer cells or be acquired as a cellular response
      to drug exposure. Resistance varies. Although regulatory approval may require
      efficacy in as few as 20% of trial cohorts, a drug may subsequently be used in
      unselected patients displaying resistance to the treatment. Principal mechanisms
      may include altered membrane transport involving the P-glycoprotein product of
      the multidrug resistance (MDR) gene as well as other associated proteins, altered
      target enzyme (e.g. mutated topoisomerase II), decreased drug activation,
      increased drug degradation due to altered expression of drug-metabolising
      enzymes, drug inactivation due to conjugation with increased glutathione,
      subcellular redistribution, drug interaction, enhanced DNA repair and failure to
      apoptose as a result of mutated cell cycle proteins such as p53. Attempts to
      overcome resistance mainly involve the use of combination drug therapy using
      different classes of drugs with minimally overlapping toxicities to allow maximal
      dosages and with narrowest cycle intervals, necessary for bone marrow recovery.
      Adjuvant therapy with P-glycoprotein inhibitors and, in specific instances, the
      use of growth factor and protein kinase C inhibitors are newer experimental
      approaches that may also prove effective in abrogating or delaying onset of
      resistance. Gene knockout using antisense molecules may be another effective way
      of blocking drug resistance genes. Conversely, drug resistance may also be used
      to good purpose by transplanting retrovirally transformed CD34 cells expressing
      the MDR gene to protect the bone marrow during high-dose chemotherapy.

PMID- 16103713
TI  - Molecular mechanisms of organelle biogenesis and related metabolic diseases.
AB  - Organelle biogenesis is regulated by transcriptional networks that modulate
      expression of specific genes encoding organellar proteins. Structural and
      functional specificity of organelles requires not only the transcription of
      specific genes and translation of resulting mRNAs, but also the transfer of
      encoded polypeptides to their site of function through signaling peptides. A
      defect in targeting of proteins to their subcellular site of function may not
      necessarily prevent biogenesis of the organelle, but would definitely lead to
      formation of a defective organelle with respect to that specific function.
      Several metabolic diseases are associated with dysfunction or defects in
      organelle biogenesis; among these, peroxisome biogenesis disorders, mitochondrial
      biogenesis defects and lysosomal storage disorders are an extensively studied
      group of genetic diseases where biogenesis of the organelle is compromised either
      due to a defect in assembly of the organelle itself or impaired import of matrix
      proteins into the organelle. Recent advances in biochemical and molecular aspects
      of biogenesis of subcellular organelles have not only unraveled the mechanisms
      for organization of cellular networks, but have also provided new insights into
      the development of metabolic diseases that are caused by disruption of organelle
      biogenesis. This article reviews the molecular mechanisms of biogenesis of
      mitochondria, lysosomes and peroxisomes in relation to the metabolic diseases of
      genetic or nongenetic origin.

PMID- 16103714
TI  - Disorders of androgen synthesis--from cholesterol to dehydroepiandrosterone.
AB  - Androgens and estrogens are primarily made from dehydroepiandrosterone (DHEA),
      which is made from cholesterol via four steps. First, cholesterol enters the
      mitochondria with the assistance of the steroidogenic acute regulatory protein
      (StAR). Mutations in the StAR gene cause congenital lipoid adrenal hyperplasia
      (lipoid CAH), a potentially lethal disease in which virtually no steroids are
      made. Lipoid CAH is common among Palestinian Arabs and people from eastern
      Arabia, and among Korean and Japanese people. Second, within the mitochondria,
      cholesterol is converted to pregnenolone by the cholesterol side chain cleavage
      enzyme, P450scc; disorder of this enzyme is very rare, probably due to embryonic
      lethality. Third, pregnenolone undergoes 17alpha-hydroxylation by microsomal
      P450c17. 17alpha-Hydroxylase deficiency, manifesting as female sexual infantilism
      and hypertension, is rare except in Brazil. Finally, 17-OH pregnenolone is
      converted to DHEA by the 17,20 lyase activity of P450c17. The ratio of the 17,20
      lyase to 17alpha-hydroxylase activity of P450c17 determines the ratio of C21 to
      C19 steroids produced. This ratio is regulated posttranslationally by at least
      three factors: the abundance of the electron-donating protein P450 oxidoreductase
      (POR), the presence of cytochrome b5 and the serine phosphorylation of P450c17.
      Mutations of POR are a new, recently described disorder manifesting as the Antley
      Bixler skeletal dysplasia syndrome, and a form of polycystic ovary syndrome.

PMID- 16103715
TI  - Mutations associated with beta-thalassemia intermedia in Kuwait.
AB  - OBJECTIVE: To identify the beta-globin gene mutations associated with beta
      thalassemia (beta-thal) intermedia in Kuwait. SUBJECTS AND METHODS: Eighteen
      patients from 13 unrelated families, mean age 12.7 +/- 8.1 years, range 4-31
      years, were involved in the study. They did not require regular blood
      transfusion. Complete blood count and cation exchange high-performance liquid
      chromatography hemoglobin quantitation were carried out using standard
      techniques. Beta-thal mutations were identified with a combination of PCR
      amplification, allele- specific oligonucleotide hybridization or direct DNA
      sequencing. The patients were also screened for the alpha2-globin gene (-3.7 kb)
      deletion. RESULTS: Of the 13 families, 4 were homozygous for the IVS-I-II (G-->A)
      and 4 for the IVS-I-6 (T-->C) mutations, while 1 each was a compound heterozygote
      for the following mutation combinations: CD 8 (-AA) and -101 (C-->T); IVS-I-6 (T-
      >C) and CD 19 (A-->G); IVS-II-1 (G-->A) and -28 (A-->C); IVS-I-110 (G-->A) and
      deltabeta0 deletion. Therefore, homozygosity for two typically mild mutations
      (IVS-II-1 and IVS-I-6) accounted for 61% of the genotypes in our patients.
      CONCLUSION: Our results indicate that screening should commence with these two
      common alleles in Kuwaiti patients presenting with beta-thal syndrome. Early
      identification of intermedia patients will avoid the complications following an
      unnecessary hypertransfusion program.

PMID- 16103716
TI  - Alpha-2-globin gene polyadenylation (AATAAA-->AATAAG) mutation in hemoglobin H
      disease among Kuwaitis.
AB  - OBJECTIVES: In the Arabian Gulf region, hemoglobin (Hb) H disease usually results
      from homozygosity or compound heterozygosity involving the alpha2-globin gene
      polyadenylation (poly A) signal (AATAAA-->AATAAG) mutation (alpha(T)alpha). Here
      we document the clinical and hemato logical characteristics of children with Hb H
      disease being followed in Kuwait. SUBJECTS AND METHODS: Twenty-four patients (0.5
      12 years old, mean 4.7 +/- 3.5 years) with persistent microcytic, hypochromic
      anemia (and normal iron status as well as normal Hb A2 levels) were referred to
      the pediatric hematology clinic for further investigations. They were all
      screened for the alpha+-thalassemia (alpha+-thal; -3.7 kb) deletion using a
      standard PCR method. They were also screened for the alpha2-globin gene
      alpha(T)alpha allele and the 5nt deletion (-alpha5nt) in the first intervening
      sequence, which are common alpha-thal alleles in this population. They were
      followed up for periods ranging from 2 to 8 years. RESULTS: Of the 24 patients, 4
      (16.7%) also had sickle cell trait (Hb-AS), while 7 (29.2%) were glucose-6
      phosphate dehydrogenase deficient. Only 1 patient had significant
      hepatosplenomegaly and 1 developed gallstones. While none was on chronic
      transfusion therapy, 8 (33.3%) had been transfused at least once and, in 3
      instances, this was secondary to parvovirus B19 +ve aplastic crisis. The alpha
      globin genotype was successfully determined in almost all patients. The results
      showed that 17 (70.8%) patients were homozygous for the poly A mutation
      (alpha(T)alpha/alpha(T)alpha), 6 (25.0%) were compound heterozygotes for this and
      the alpha+-thal (-3.7 kb) deletion (-alpha/alpha(T)alpha) and 1 (4.2%) was
      undetermined. There were no significant differences in the phenotypes of the 2
      genotypes and their hematological features were identical. CONCLUSIONS: Hb H
      disease involving the poly A mutation is a mild thal intermedia phenotype among
      Kuwaitis. There are no serious complications and there is no need for regular
      blood transfusion.

PMID- 16103717
TI  - Phenotypic and molecular characterization of Candida dubliniensis isolates from
      clinical specimens in Kuwait.
AB  - OBJECTIVE: This study was carried out to characterize Candida dubliniensis using
      phenotypic and molecular methods and to determine the occurrence of C.
      dubliniensis in clinical specimens in Kuwait. MATERIALS AND METHODS: A total of
      880 clinical specimens for isolation of fungi were processed according to
      standard procedures. Of these, 390 germ-tube-positive clinical isolates of
      Candida species were examined for rough colonies with hyphal fringes and
      chlamydospore production on simplified sunflower seed agar for their presumptive
      phenotypicidentification as C. dubliniensis. The identification of C.
      dubliniensis isolates was further confirmed by the Vitek 2 yeast identification
      system, semi-nested (sn) PCR amplification of high-copy rDNA and direct DNA
      sequencing of the internally transcribed spacer 2 (ITS2) region. RESULTS: Of the
      390 isolates of Candida species investigated, 12 were identified as C.
      dubliniensis, giving an overall occurrence of 3%. All the C. dubliniensis
      isolates formed rough colonies with hyphal fringes and abundant chlamydospores on
      sunflower seed agar, did not assimilate trehalose, lactate and alpha-methyl-D
      glucoside, and were isolated from human immunodeficiency virus (HIV)-negative
      patients. Four C. dubliniensis isolates utilized D-xylose. The species-specific
      primer derived from the ITS2 sequence of C. dubliniensis and used together with
      the panfungal reverse primer in the reamplification step of the snPCR
      specifically amplified rDNA from reference and clinical C. dubliniensis isolates
      and not from C. albicans or other Candida species. The identity of two
      representative isolates was confirmed by DNA sequencing of the ITS2 region.
      CONCLUSIONS: The identity of 12 C. dubliniensis isolates was first established by
      phenotypic characteristics and then by snPCR using species-specific primers
      derived from ITS2 sequences. The recovery of C. dubliniensis from HIV-negative
      patients from Kuwait reinforces the existing view that this novel yeast species
      has a worldwide distribution and its occurrence is not restricted to any
      particular immunocompromised population.

PMID- 16103718
TI  - Instability of chimaeric antibody secretion by anti-carcinoembryonic antigen
      producing hybridoma cells after gene targeting.
AB  - OBJECTIVE: To produce a chimaeric version of the 11-285-14 anti-carcinoembryonic
      antigen (CEA) monoclonal antibody using a gene targeting approach. MATERIALS AND
      METHODS: A replacement vector was constructed to insert the human constant gamma1
      gene within the mouse heavy chain locus of 11-285-14 hybridoma cells. The mouse
      constant gamma1 gene (1.5 kb) and the mouse mu intron fragment (2.2 kb) were
      amplified by PCR and cloned into a pKO Scrambler vector. The human constant
      gamma1 gene fragment (2.2 kb) was cloned next to the intron fragment. Resistant
      colonies were screened by ELISA for the presence of the human isotype in their
      supernatants. RESULTS: Of the 4,370 resistant colonies obtained, 87 colonies
      showed secretion of the human isotype at levels between 4 and 32 ng/ml. PCR and
      Southern blot results confirmed the correct integration of the human gene by
      homologous recombination within the heavy chain locus. Most of the producers
      ceased to express the human isotype within a few weeks after the initial positive
      ELISA results. Instability of secretion could not be explained by genetic
      instability in all the clones, which suggests the presence of other undefined
      epigenetic or physiologic mechanisms. CONCLUSION: Gene targeting resulted in
      transformants with unstable and low production rates of chimaeric anti-CEA
      antibody.

PMID- 16103719
TI  - Very-long-chain fatty acids activate lysosomal hydrolases in neonatal human skin
      tissue.
AB  - OBJECTIVE: The aim of this study was to examine the in vitro effect of
      peroxisomal dysfunction on lysosomal enzymes, the autophagic machinery in the
      cell, in order to understand the mechanisms of pathogenesis of peroxisomal
      disorders. MATERIALS AND METHODS: Foreskin samples were obtained immediately
      after circumcision of 1- to 2-day-old infants at the Maternity Hospital, Kuwait.
      Skin tissues were cleaned, cut into slices of 1-2 mm2 in size and treated with
      lignoceric acid (1-20 microg/ml), a very-long-chain fatty acid (VLCFA), in the
      presence or absence of 1-5 mM aminotriazole (ATZ). A battery of lysosomal enzymes
      were assayed following treatment of dermal tissue with VLCFA or ATZ. RESULTS:
      Treatment of skin slices with lignoceric acid significantly increased (p < 0.001)
      the enzymic activities of acid lipase, acid phosphatase, alpha-glucosidase, alpha
      galactosidase, N-acetyl-alpha-D-glucosaminidase (NAGA) and N-acetyl-alpha-D
      galactosaminidase (NAGTA). ATZ (1-5 mM), an inhibitor of key peroxi somal enzyme
      catalase, also markedly increased the enzymic activities of acid phosphatase,
      alpha-glucosidase (23%) and alpha-galactosidase (18%) without any significant
      effect on NAGA or NAGTA. Western blot analysis further revealed that both VLCFA
      and ATZ significantly increased the protein expression of lysosomal enzymes, beta
      galactosidase and beta-glucuronidase. CONCLUSION: Experimen tal dysfunction of
      peroxisomes mimicked by elevated VLCFA or ATZ-mediated catalase inhibition
      significantly increased the activities of lysosomal hydrolases in human dermal
      tissue, suggesting that activation of the lysosomal system could be one of the
      factors responsible for cellular damage during pathogenesis of peroxisomal
      diseases.

PMID- 16103720
TI  - A high calcium-phosphate product is associated with high C-reactive protein
      concentrations in hemodialysis patients.
AB  - BACKGROUND: An elevated CaxPO4 product and C-reactive protein (CRP) have been
      associated with coronary artery calcification and increased cardiovascular
      mortality in hemodialysis (HD) patients. However, it has not been defined, so
      far, whether and how both parameters are related to each other. For this reason
      we have evaluated in a cross-sectional and in an interventional study the
      possible correlation between CaxPO4 and CRP and the effect of the correction of a
      high CaxPO4 on CRP levels. METHODS: 47 uremic patients (age 65 +/- 16 years) on
      regular chronic HD were selected from a total population of 125 prevalent
      patients treated at our Institution. Patients had no clinical evidence of either
      acute infectious or inflammatory diseases for at least 4 weeks before the study.
      They were on regular bicarbonate HD for 6-329 months (median 42). CRP, hemoglobin
      (Hb), serum albumin (sAlb), protein catabolic rate (PCRn), serum calcium (Ca),
      serum phosphorus (PO4), CaxPO4, intact PTH, Kt/V, presence of ischemic heart
      disease (IHD) and/or peripheral vascular disease (PVD) were recorded. CRP was Ln
      transformed in all statistical analyses because of positive skewness. RESULTS:
      The main findings were: LnCRP 2.17 +/- 0.77 mg/l, Ca 10.1 +/- 0.4 mg/dl, PO4 5.8
      +/- 0.6 mg/dl, CaxPO4 59 +/- 6 mg2/dl2, andPTHint 218 +/- 195 ng/ml. 18/47 had
      IHD, 18/47 PVD. A significant hyperbolic correlation between CaxPO4 and CRP was
      observed. A piecewise linear regression model analysis identified a break-point
      for CaxPO4 at 55 mg2/dl2. Comparison of CRP levels after the division of the
      patients into two groups according to CaxPO4 break-point (group A, CaxPO4 < or =
      55 mg2/dl2, n = 16 patients; group B, CaxPO4 >55 mg2/dl2, n = 31 patients) showed
      that CRP levels were significantly lower in patients in group A (LnCRP 1.43 +/-
      0.22 mg/l) than in group B (LnCRP 2.55 +/- 0.67 mg/l, p < 0.0001). Multiple
      regression analysis bearing LnCRP as dependent variable confirmed CaxPO4 as the
      most significant variable among the other variables examined. In 22 patients with
      CaxPO4 > or = 60 mg2/dl2, we performed intensive lowering of the CaxPO4 product
      in order to reach and maintain a CaxPO4 , or =55 mg2/dl2 for 3 months. At the end
      of observation, a significant reduction in CaxPO4 and LnCRP was observed (CaxPO4
      pre 62.8 +/- 1.9 vs. post 46.3 +/- 6.2 mg2/dl2: p < 0.0001; LnCRP pre 2.32 +/
      0.36 vs. post 1.83 +/- 0.14 mg/l: p < 0.0001). No significant variation in the
      other biochemical parameters was observed. CONCLUSIONS: Our data show that in
      chronic HD patients in steady clinical conditions with no clinical evidence of
      either infectious or inflammatory diseases, a high CaxPO4 is associated with high
      CRP concentrations. Intensive lowering of CaxPO4 reduces CRP

PMID- 16103721
TI  - The impact of an out-reach clinic on referral of patients with renal impairment.
AB  - BACKGROUND: Early diagnosis and prompt treatment of a number of renal diseases
      may delay renal failure, obviate the need for renal replacement therapy and
      reduce co-morbidity. The aim of this study was to examine the impact of out-reach
      renal clinics on patterns of referral of patients with renal impairment to a
      nephrologist. METHODS: The number of patients with renal impairment was
      determined as defined by serum creatinine levels >150 micromol/l in three centres
      within a single NHS trust over two separate 1-week periods. None of the centres
      studied has a local nephrologist, however one centre (hospital A) has renal out
      reach clinics, another is geographically close to a renal unit (hospital B),
      while the third unit (hospital C) has no nephrology presence and is
      geographically furthest from the renal unit. In addition, retrospective as well
      as follow-up data on the renal function of all patients with renal impairment was
      collected. RESULTS: In hospital A, there was a lower proportion of patients with
      unreferred renal impairment than in the other two hospitals. Within the
      unreferred patient group there were significantly more patients whose renal
      function improved during the follow-up period. A considerable proportion of
      patients with documented deterioration in renal function remained unknown to
      nephrology services 6 months after initial presentation. Other than the presence
      of an onsite nephrology service, the only other factor found to be significantly
      different in those patients not referred to nephrologists was age: as in all
      three centres, those not referred were significantly older. CONCLUSION: Inequity
      of access to renal services is an important obstacle to early referral of
      patients with impaired renal function. Out-reach renal services provide a model
      which significantly improves referral patterns.

PMID- 16103722
TI  - Effect of L-carnitine on the serum lipoproteins and HDL-C subclasses in
      hemodialysis patients.
AB  - AIMS: Following carnitine administration a decrease in plasma levels of
      triglyceride (TG) and increase in total high-density lipoprotein cholesterol (HDL
      C) has been reported. Our hypothesis was that it also improves the HDL2/HDL3
      ratio, symptomatic intradialytic hypotension, and anemia in hemodialysis (HD)
      patients. METHODS: Forty HD patients with a mean (+/- SD) age of 53 +/- 13 years
      were treated with 500 mg/day carnitine taken orally for 2 months. Patients were
      used as their own controls (before treatment). Lipid and lipoproteins were
      determined by Alcyon Abbott autoanalyzer. HDL subclasses were measured by
      magnesium precipitation after fractionation with dextran sulfate. Hemoglobin,
      hematocrit and serum albumin were measured by standard methods. The results were
      analyzed by SPSS 11.05. RESULTS: We found a significant decrease in serum TG
      (2.22 +/- 0.99 vs. 1.93 +/- 1.07 mmol/l, p < 0.01) and VLDL-C (0.93 +/- 0.36 vs.
      0.81 +/- 0.34 mmol/l, p = 0.01) and a marked increase in HDL-C (0.9 +/- 0.16 vs.
      1.06 +/- 0.24 mmol/l, p < 0.05), HDL2-C (0.17 +/- 0.06 vs. 0.27 +/- 0.14 mmol/l,
      p < 0.05) and albumin (37 +/- 4 vs. 42 +/- 5 g/l, p = 0.01) levels. The serum
      levels of total cholesterol (4.61 +/- 0.89 vs. 4.5 +/- 0.95 mmol/l, p = 0.1), LDL
      C (2.78 +/- 0.85 vs. 2.6 +/- 0.89 mmol/l, p > 0.05), HDL3-C (0.73 +/- 0.1 vs.
      0.79 +/- 0.17 mmol/l, p > 0.05), hemoglobin, hematocrit, and intradialytic blood
      pressure did not change after the treatment. CONCLUSION: Treatment with 500
      mg/day carnitine taken orally for 2 months reduces serum levels of TG and VLDL-C,
      and increases HDL-C, HDL2-C and albumin in HD patients.

PMID- 16103723
TI  - Association between hyperhomocysteinemia and ultrasonographic atherosclerotic
      indices of carotid arteries in chronic hemodialysis patients.
AB  - BACKGROUND: Atherosclerotic cardiovascular events are a major cause of morbidity
      and the main cause of mortality in hemodialysis patients. Hyperhomocysteinemia-
      which is a consistent finding in uremic patients--is considered an independent
      risk factor for cardiovascular disease (CVD). However, the relationship between
      plasma homocysteine (Hcy) concentrations and atherosclerotic CVD has not been
      extensively investigated. PATIENTS AND METHODS: 37 patients undergoing chronic
      hemodialysis and 30 healthy individuals (control group), sex- and age-matched,
      were included in this study. Both healthy controls and hemodialysis patients
      underwent echo-Doppler carotid artery examination. The right and left carotid
      arteries were assessed separately. Our observation included measurements of the
      ultrasound images of the intimal wall thickness, the lumen diameter and the
      atherosclerotic plaques. We determined plasma Hcy, vitamin B12 and folic acid
      levels and serum cholesterol, triglycerides, HDL, ApoA-I, ApoB-100, Lp(a), CRP,
      albumin and creatinine levels in blood samples from both studied groups. We also
      determined the urea reduction ratio in the patient groups. The epidemiological as
      well as the biochemical data were correlated with the findings of the carotid
      artery examination. RESULTS: Plasma Hcy levels were significantly increased in
      hemodialysis patients compared to controls (33 +/- 12.3 vs. 12.27 +/- 7.47
      micromol/l, p < 0.001). Intimal wall thickness, lumen diameter and number of
      atherosclerotic plaques of both carotid arteries were significantly higher (p <
      0.01 or p < 0.001) in patients compared to controls. There was a significant
      positive correlation between plasma Hcy levels and the number of the
      atherosclerotic plaques (r = 0.41, p < 0.01 in the right and r = 0.49, p < 0.001
      in the left carotid artery). Lumen diameter was significantly (p < 0.01)
      associated with age, MAP and CRP levels. Significant correlations (p = 0.05-0.01)
      were also found between the number of the plaques and age as well as the duration
      of hemodialysis, while folic acid levels were inversely correlated with the
      number of the plaques. CONCLUSIONS: Both hyperhomocysteinemia and atherosclerotic
      indices of the carotid arteries are more prevalent in hemodialysis patients
      compared to healthy controls. Elevated plasma Hcy levels were associated with the
      carotid artery atherosclerotic indices in chronic hemodialysis patients.

PMID- 16103724
TI  - Is hyperhomocysteinemia a contributor to atherosclerosis in chronic kidney
      disease patients?

PMID- 16103725
TI  - Serum C-reactive protein level is associated with renal function and it affects
      echocardiographic cardiovascular disease in pre-dialysis patients.
AB  - BACKGROUND: Relevance of serum CRP for morbidity and mortality in pre-dialysis
      patients has not been assessed extensively. The aim of this study was to
      determine the incidence of elevated serum CRP in pre-dialysis patients and to
      identify the factors that associate with serum CRP. We were also evaluated the
      effects of serum CRP on cardiovascular disease, anemia, and nutritional markers.
      METHODS: One hundred and eight pre-dialysis patients with a mean creatinine
      clearance (CrCl) of 30.1 ml/min were included in the study. Data collected from
      each patient included demographics, co-morbidity, medications, blood pressures,
      blood biochemistry including serum CRP, renal function, and echocardiography.
      RESULTS: Serum CRP was elevated (>5 mg/l) in 43 patients (39.8%). There was a
      negative correlation between serum CRP and CrCl (r = -0.370, p < 0.001). CrCl was
      the unique independent factor affecting serum CRP. Serum CRP was an independent
      factor affecting left ventricular mass index, fractional shortening, serum
      albumin and hematocrit in multivariate analyses. CONCLUSIONS: Prevalence of
      elevated serum CRP in pre-dialysis patients is high. Reduced renal clearance of
      CRP and/or cytokines may contribute to the inflammatory status. Elevated serum
      CRP is an important cause of morbidity in pre-dialysis patients.

PMID- 16103726
TI  - Could we reduce the prevalence of inflammation among patients with chronic kidney
      disease?

PMID- 16103727
TI  - The Rush Memory and Aging Project: study design and baseline characteristics of
      the study cohort.
AB  - The long-term objective of the Rush Memory and Aging Project is to identify the
      postmortem indices linking genetic and environmental risk factors to the
      development of Alzheimer's disease (AD). The overall study design involves a
      detailed assessment of risk factors for AD in older persons without known
      dementia who agree to annual clinical evaluation and organ donation at the time
      of death. In contrast to other clinical-pathologic studies which are conducted on
      special populations, the Rush Memory and Aging Project enrolled a cohort with
      much greater diversity in terms of educational attainment, in addition to gender,
      race, and ethnicity. From September of 1997 through April of 2005, more than
      1,000 older persons without known dementia from more than 30 residential
      facilities across the Chicago metropolitan area agreed to participate. Their mean
      age was 81 years, about a third had 12 or fewer years of education, a third were
      men, and about 10% were members of a racial or ethnic minority group. More than
      950 already have completed their baseline clinical evaluation.

PMID- 16103728
TI  - Amyotrophic lateral sclerosis mortality in 1.9 million US cancer survivors.
AB  - BACKGROUND: Large cancer registries offer the opportunity to explore and generate
      hypotheses about the pathogenesis of cancer and other diseases, including
      neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). METHODS:
      Using data from nine population-based cancer registries of the Surveillance,
      Epidemiology, and End Results (SEER) Program of the US National Cancer Institute
      (NCI) and death certificates, we followed 1.9 million cancer survivors who were
      diagnosed between 1973 and 2000 and who survived at least 1 year, through the
      year 2000. The outcome of interest was the standardized mortality ratio (SMR) of
      observed to expected ALS deaths among cancer survivors. To assess the validity of
      the study design, we also examined associations with Parkinson's disease
      mortality, which we expected to be inversely associated with smoking-related
      cancers. RESULTS: There was no significantly increased risk or deficit of ALS
      mortality for all cancer sites combined (SMR = 1.0). Parkinson's disease
      mortality was, as expected, significantly and inversely associated with smoking
      related cancers. Both ALS and Parkinson's disease mortality were significantly
      elevated following melanoma (SMR = 1.6; 95% CI = 1.1-2.2; SMR = 1.5; 1.2-1.8,
      respectively). Contrary to previous hypotheses, ALS was unrelated to lymphomas or
      lymphoproliferative malignancies and was not associated with smoking-related
      cancers. CONCLUSIONS: In this exploratory study, we observed a modest,
      significant association between melanoma and both ALS and Parkinson's disease
      mortality. It would be useful to explore these findings in other large national
      databases that are able to link cancer and ALS and Parkinson's disease.

PMID- 16103729
TI  - The Aging, Demographics, and Memory Study: study design and methods.
AB  - OBJECTIVE: We describe the design and methods of the Aging, Demographics, and
      Memory Study (ADAMS), a new national study that will provide data on the
      antecedents, prevalence, outcomes, and costs of dementia and "cognitive
      impairment, not demented" (CIND) using a unique study design based on the
      nationally representative Health and Retirement Study (HRS). We also illustrate
      potential uses of the ADAMS data and provide information to interested
      researchers on obtaining ADAMS and HRS data. METHODS: The ADAMS is the first
      population-based study of dementia in the United States to include subjects from
      all regions of the country, while at the same time using a single standardized
      diagnostic protocol in a community-based sample. A sample of 856 individuals age
      70 or older who were participants in the ongoing HRS received an extensive in
      home clinical and neuropsychological assessment to determine a diagnosis of
      normal, CIND, or dementia. Within the CIND and dementia categories, subcategories
      (e.g. Alzheimer's disease, vascular dementia) were assigned to denote the
      etiology of cognitive impairment. CONCLUSION: Linking the ADAMS dementia clinical
      assessment data to the wealth of available longitudinal HRS data on health,
      health care utilization, informal care, and economic resources and behavior, will
      provide a unique opportunity to study the onset of CIND and dementia in a
      nationally representative population-based sample, as well as the risk factors,
      prevalence, outcomes, and costs of CIND and dementia.

PMID- 16103730
TI  - Stroke etiology among Haitians living in Miami.
AB  - The black Caribbean population continues to grow in the US and little is known
      about stroke etiologies in that community. We examined stroke subtypes in 175
      consecutive Haitian-born patients living in Miami, admitted for acute stroke.
      Ischemic stroke was diagnosed in 72%. Small vessel occlusion was the most
      frequent stroke subtype. There was a high prevalence of hypertension, medication
      noncompliance and intracranial atherosclerosis. Hypertension was the only
      cardiovascular risk factor significantly associated with small vessel infarction
      when compared with non-small vessel infarcts.

PMID- 16103731
TI  - Therapeutic mechanism of Saikosaponin-d in anti-Thy1 mAb 1-22-3-induced rat model
      of glomerulonephritis.
AB  - AIMS: Mesangioproliferative glomerulonephritis is a common kidney disease and at
      present, there is no effective treatment. Our previous studies have demonstrated
      that Sairei-to can significantly prevent progression of experimental
      glomerulonephritis in rats. Although we have reported that the active component
      of Sairei-to in treatment of glomerulonephritis was Saikosaponin-d (Ssd),
      mechanism of Ssd in prevention of mesangioproliferative glomerulonephritis
      progression is still unknown. Therefore, current study examines the effects of
      Ssd on progression of mesangioproliferative glomerulonephritis induced by anti
      Thy1 monoclonal antibody 1-22-3 (mAb 1-22-3) in uninephrectomized rats. METHODS:
      Eighteen female Wistar rats first received uninephrectomy and mAb 1-22-3
      injection and were then divided into 3 groups: treated daily with phosphate
      buffered saline (PBS), 0.6 or 1.8 mg/kg of Ssd. Urinary protein concentration and
      systolic blood pressure were evaluated and the kidneys were collected and
      subjected to histological and immunohistological evaluation. The mRNA and protein
      of the kidneys were extracted and subjected to reverse transcriptase polymerase
      chain reaction and Western blot analysis, respectively. RESULTS: Ssd reduced the
      amount of urinary protein and systolic blood pressure. Ssd administration also
      decreased extracellular matrix expansion, crescentic formation as well as
      infiltration of macrophages and CD8+ T lymphocytes. Moreover, Ssd significantly
      reduced expression of transforming growth factor beta 1 (TGF-beta1) and type I
      collagen in the kidneys. CONCLUSION: Ssd inhibits the progression of
      mesangioproliferative glomerulonephritis through reduction of the expression of
      TGF-beta1 and the infiltration of macrophages and CD8+ T lymphocytes.

PMID- 16103732
TI  - Tacrolimus and cyclosporinein vitro and in vivo induce osteopontin mRNA and
      protein expression in renal tissues.
AB  - The mechanism of immunosuppression-linked nephrotoxicity in organ transplantation
      remains to be solved. Expression of osteopontin (OPN), a multifunctional secreted
      glycoprotein, has been associated with various forms of renal injuries. In this
      study, using in vitro and in vivo models, we examined the effects of cyclosporine
      (CsA) and tacrolimus (TAC) on OPN mRNA and protein expression. We also examined
      if CsA- and TAC-induced OPN expression is dependent on transforming growth factor
      (TGF)-beta expression. For in vivo experiments mice and rats were injected with
      CsA (25 mg/kg) and TAC (0.2 mg/kg). For in vitro experiments, human proximal
      tubular epithelial (PTE) cells were treated with CsA and TAC for 4 h. To study
      the in vivo effect of TGF-beta on OPN mRNA, mice were injected with recombinant
      TGF-beta protein (3 mg/kg). The expression of OPN was also studied in CsA-treated
      PTE cells with and without anti-TGF-beta antibody. At the end of in vitro and in
      vivo treatments, RNA was isolated from kidney tissue and renal cells reverse
      transcribed to cDNA and amplified for OPN mRNA. Using immunochemistry and Western
      blot analysis OPN protein expression was also studied in vivo and in vitro,
      respectively. Both in vitro and in vivo treatment with CsA and TAC resulted in
      significantly increased OPN mRNA and protein expression. TGF-beta treatment in
      vivo also resulted in a significantly increased OPN mRNA expression and anti-TGF
      beta antibody but not the control antibody in vivo in CsA-treated mice, and in
      vitro in CsA-treated PTE cells inhibited OPN mRNA expression. OPN may contribute
      to the CsA- and TAC-induced nephrotoxicity in organ transplant recipients and the
      increased OPN expression might be mediated by TGF-beta.

PMID- 16103733
TI  - Mouse anterior pituitary gland: analysis by ion trap mass spectrometry.
AB  - We investigated the proteome of the anterior pituitary gland (AP) in a species in
      which the genome has been sequenced. Subcellular fractions of APs from 2-month
      old male mice were prepared for protein denaturation, treatment with trypsin and
      analyses utilizing micro liquid chromatography tandem mass spectrometry and the
      database search software SEQUEST. In the nuclear, non-nuclear 100,000 g and
      cytosolic fractions, we identified 49, 36 and 68 different proteins,
      respectively. A total of 115 distinct proteins were detected. We identified
      growth hormone, prolactin, pro-opiomelanocortin, the alpha-subunit for the
      glycoprotein hormones, and luteinizing hormone-beta. Groups of other identified
      proteins included hormone-processing, secretion granule-associated, non-hormonal
      endoplasmic reticulum-associated, calcium-binding, protein kinase C-associated,
      histones, non-histone chromosomal, other RNA-binding, heterogeneous nuclear
      ribonucleoproteins, splicing factors, helicases, lamins, ribosomal, microtubule
      associated, microfilament-associated, adenosine triphosphate- and guanosine
      triphosphate-associated, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase
      activation, enzymes in glycolysis and the tricarboxylic and urea cycles and the
      pentose phosphate path, heat-shock, glutathione-associated, peroxidases,
      ubiquitin-associated, catabolic, protease inhibitors, other, and blood proteins.
      The 115 proteins reported in this study and the 145 proteins reported in a
      previous study on the AP of the adult male Golden Syrian hamster are compared and
      form a foundation for defining the proteome in normal adult male AP.

PMID- 16103734
TI  - In vivo study to evaluate the protective effects of amifostine on radiation
      induced damage of testis tissue.
AB  - OBJECTIVE: To investigate the early protective effects of amifostine against
      radiation-induced damage on rat testis tissue. METHODS: Eighty adult male Wistar
      rats were randomized to 4 groups: Saline solution was given to group A for
      control, 200 mg/kg amifostine (WR-2721) to group B, a single fraction of 6 Gy
      local irradiation to testes in group C and 200 mg/kg amifostine 15-30 min before
      6 Gy testicular irradiation to group D. Animals were sacrificed 3 weeks after
      treatment and their testes were removed for macroscopic, microscopic and
      ultrastructural histopathological examination. RESULTS: The weights, widths and
      lengths of testes in the last 3 groups had decreased significantly when compared
      with the control group, but the decrease in widths after irradiation was found to
      be significantly less only in the amifostine plus radiation group. There was a
      significant reduction of testis weights in relation to the individual body
      weights in the irradiated testes compared with the other groups (p < 0.005),
      while there was no significant change of testis weight/total body weight ratio in
      amifostine plus irradiation group. Spermatogonium A and primary spermatocyte
      counts were also less in the treatment groups, and primary spermatocyte numbers
      were significantly higher in amifostine plus radiation group when compared with
      radiation alone group (p < 0.005). Pretreatment with amifostine reduced the
      decrease of primary spermatocyte counts by a factor of 1.28. Electron microscopic
      analysis did not show any cytotoxic effect of amifostine alone, and furthermore,
      ultrastructural findings were normal with the addition of amifostine prior to
      irradiation, though there was damage in the radiation exposure group. CONCLUSION:
      Amifostine when given alone by itself appears to cause adverse alterations in
      testis tissue; however, it has a radioprotective effect on spermiogenetic cells
      when used prior to radiation.

PMID- 16103735
TI  - Anti-progressive effect of neutral endopeptidase 24.11 (NEP/CD10) on cervical
      carcinoma in vitro and in vivo.
AB  - OBJECTIVES: Neutral endopeptidase 24.11 (NEP) is known to play important roles in
      the maintenance of homeostasis or in neoplastic transformation and tumor
      progression in certain human malignancies through the enzymatic inactivation of
      bioactive peptides such as endothelin-1 (ET-1), angiotensin-II, and bombesin.
      METHODS: In this study, we first investigated NEP expression in cervical
      carcinoma by immunohistochemical staining and Western blot analysis. Next, we
      examined NEP functions in vitro and in vivo by generating NEP-overexpressing
      cervical carcinoma cells. RESULTS: We found a significant decrease in cellular
      proliferative and invasive abilities with a reduced ET-1 concentration in the
      conditioned medium by NEP overexpression in cervical carcinoma CaSki cells, which
      have an ET-1 autocrine loop. In addition, these potentials were cancelled by
      blockade of NEP activity with a specific inhibitor. Although vector-transfected
      CaSki cells could grow even in serum-free media, NEP-overexpressing cells failed
      to proliferate in these media. Furthermore, we demonstrated that NEP suppressed
      tumor formation of subcutaneous xenografts using nude mice. CONCLUSIONS: Our
      results indicated that NEP functions as a tumor-suppressor gene in cervical
      carcinoma cells, and its expression may have prognostic significance. Further
      elucidation of the mechanism underlying the observed effect of NEP will
      contribute to a better understanding of its role in the pathophysiology of
      cervical carcinoma.

PMID- 16103736
TI  - Correlation between laminin-5 gamma2 chain and epidermal growth factor receptor
      expression in esophageal squamous cell carcinomas.
AB  - OBJECTIVES: Laminin-5 gamma2 chain (LN-5 gamma2) is an extracellular matrix
      protein that plays an important role in cell migration and tumor invasion. We
      evaluated the association of LN-5 gamma2 and epidermal growth factor receptor
      (EGFR) expression in esophageal squamous cell carcinoma (SCC). METHODS: LN-5
      gamma2 and EGFR expression was evaluated in 110 esophageal SCC patients by
      immunohistochemistry, and was confirmed using esophageal SCC cell lines by
      Western blot analysis. RESULTS: LN-5 gamma2 expression in the invasive front of
      the tumor was correlated with the depth of invasion (p = 0.0001), lymph node
      metastasis (p = 0.0011) and pathological stage (p = 0.0001). The strong
      expression of EGFR was also correlated with lymph node metastasis (p = 0.0456)
      and the pathological stage (p = 0.0055). In patient survival, LN-5 gamma2
      positivity and/or strong EGFR expression showed a significantly low survival rate
      as compared with those with lesser expression of LN-5 gamma2 and EGFR.
      Immunohistochemically, LN-5 gamma2 expression was significantly correlated with
      EGFR expression (p < 0.0001). Western blot analysis also confirmed the correlated
      expression of LN-5 gamma2 and EGFR in SCC cell lines except 2 of the 5 cell
      lines. CONCLUSIONS: This study suggests that coexpression of LN-5 gamma2 and EGFR
      is closely related to the progression and poor prognosis of esophageal SCC.

PMID- 16103737
TI  - Lactoferrin expression by bovine ocular surface epithelia: a primary cell culture
      model to study lactoferrin gene promoter activity.
AB  - Tear lactoferrin, mainly secreted by the lachrymal glands, exerts a protective
      effect on the ocular surface, and an abnormal decrease of its production may lead
      to an increased risk of infection and pathological alterations of ocular surface
      epithelia. In this study we analyzed whether corneal and conjunctival epithelia
      could be an additional source of tear lactoferrin, and whether conjunctival
      epithelial cells in culture could be a suitable model system to address
      regulation of lactoferrin gene expression. Real-time PCR and Western
      immunoblotting showed that in bovines lactoferrin is indeed produced by these
      epithelia, and that the human lactoferrin promoter can direct the expression of a
      CAT reporter gene, thus indicating that these cells are a true source of
      lactoferrin, and may be used in vitro to study the regulation of lactoferrin
      expression.

PMID- 16103738
TI  - Revised uvulopalatopharyngoplasty with uvula preservation and its clinical study.
AB  - OBJECTIVES: A revised uvulopalatopharyngoplasty (UPPP) is reported for reducing
      the surgical complications without compromising the response. METHODS AND
      MATERIALS: A new method of performing UPPP was designed, in which the uvula is
      preserved, but a larger portion of the soft palate is removed. This new procedure
      is called the 'revised UPPP with uvula preservation' (Han's UPPP or H-UPPP), the
      characteristics of which are as follows: complete preservation of the uvula;
      larger portion of the soft palate resected (with the levator palati and tensor
      palati remaining intact); the adipose tissue in the space of the velum palati is
      removed; the preserved uvula will become a 'normal' one by the contraction of
      scar tissue on both sides of the musculus palato-uvularis and the lower margin of
      the tensor palati. 68 cases of obstructive sleep apnea/hypopnea syndrome had been
      treated with H-UPPP between September 1998 and May 2001. RESULTS: Polysomnography
      was performed for all 68 cases 6 months postoperatively with a surgical response
      of 69.12%, defined as a >50% reduction of the apnea-hypopnea index and <20 apneic
      pauses/h; no palatopharyngeal incompetency or palatopharyngeal stenosis. Anatomic
      measurements showed that the preserved uvula in H-UPPP begins to retract 2 weeks
      postoperatively, and the preserved uvula becomes 'normal' in 3-6 months.
      CONCLUSIONS: These results suggest that H-UPPP is an effective surgery and
      produces fewer complications compared with the classic UPPP.

PMID- 16103739
TI  - Contemporary management of pancreatic pseudocysts.

PMID- 16103740
TI  - 'It's important to know when to turn back' - an interview with Albert Lowenfels
      by Martin E. Fernandez-Zapico.
AB  - Dr. Albert Lowenfels made outstanding contributions to the understanding of
      pancreatic diseases. His exceptional achievements in the field of pancreatic
      epidemiology were seminal for the characterization of lifestyle factors such as
      smoking, drinking and obesity in the pathogenesis of pancreatic diseases. In this
      interview, Dr. Lowenfels shares with Pancreatology his experience as pancreatic
      researcher.

PMID- 16103741
TI  - Effects of a new isoquinolinone derivative on induction of action potential
      bursts in central snail neuron.
AB  - The effects of 7-bromo-1,4-dihydro-2-phenyl-4,4-bis(4-pyridinylmethyl)2H
      isoquinolin-3-one dihydrochloride (BDPBI) on induction of action potential bursts
      were studied pharmacologically on the RP4 central neuron of the giant African
      snail (Achatina fulica Ferussac). The effects of m-3M3FBS, a phospholipase
      activator and HTMT, a histamine (H1) receptor agonist, on the neuron were also
      tested. The RP4 neuron showed spontaneous firing of action potential.
      Extracellular application of BDPBI (150 micromol/l) reversibly elicited bursts of
      potential (BoP) on the neuron. m-3M3FBS and HTMT also elicited BoP on the RP4
      neuron. The BoP elicited by BDPBI were blocked by U73122 (6 micromol/l), a
      compound commonly used as a phospholipase C (PLC) inhibitor. Neomycin (3.5
      mmol/l), a high-magnesium solution (30 mmol/l), replacing the physiological
      sodium ion with lithium ion or adding diphenhydramine, chloropheniramine
      decreased the BoP elicited by BDPBI. The BoP elicited by BDPBI were not inhibited
      after administration with (1) prazosin, propranolol, atropine, d-tubocurarine,
      hexamethonium, haloperidol, cimetidine, (2) calcium-free solution, (3) high
      potassium (12 mmol/l) solution, and (4) pretreatment with KT-5720. The BoP
      elicited by HTMT was not inhibited after administration of diphenhydramine or
      chloropheniramine. Voltage-clamped studies revealed that BDPBI decreased the
      amplitudes of calcium and steady-state outward currents while it did not alter
      the amplitude of the fast inward current. No negative slope relationship of the
      steady-state current voltage relationship was found in BDPBI-treated neurons. It
      is concluded that BDPBI reversibly elicited BoP in the central snail neuron. The
      effect was not due to (1) the extracellular calcium ion fluxes, or (2) the
      activation of cholinergic, adrenergic or histamine receptors. The BDPBI-elicited
      BoP were dependent on the phospholipase activity in the neuron.

PMID- 16103742
TI  - Influence of sodium valproate on sodium and chloride urinary excretion in rats,
      gender differences.
AB  - Evidence exists indicating that sodium valproate (VPA) increases diuresis in
      rats. The chloriuretic and natriuretic effect of VPA has not previously been
      investigated, so the aim of the present study was to define the peculiarities of
      24-hour urinary sodium (Na) and chloride (Cl) excretion in young adult Wistar
      rats of both genders, and to evaluate the effects of VPA. 24-hour urinary Na, Cl,
      creatinine and pH levels were measured in 28 control intact Wistar rats and 26
      Wistar rats after a single intragastric administration of 300 mg/kg VPA. After
      VPA administration, 24-hour diuresis and 24-hour diuresis per 100 g of body
      weight were significantly higher in VPA rats of both genders. 24-hour urine Na
      and Cl excretion were significantly higher in VPA male and VPA female rats than
      in gender-matched controls. The 24-hour urinary Cl excretion was found to be
      significantly higher in VPA male than in VPA female rats. The study data show
      that VPA, alongside the diuretic effect, enhances Na and Cl excretion with urine.
      The 24-hour chloriuretic response to VPA in male rats was significantly higher
      than in female rats. The mechanism of such a gender-related effect is not yet
      clear.

PMID- 16103743
TI  - Serum PDGF-AB in pleural mesothelioma.
AB  - Overexpression of platelet-derived growth factor (PDGF) has been observed in lung
      and pleural tumors. The aim of this study was to evaluate the diagnostic and
      prognostic role of serum PDGF in pleural mesothelioma (PM). Four groups of
      subjects were studied: 93 malignant PM patients, 33 primary non small cell lung
      cancer patients, 51 subjects exposed to asbestos, defined as high-risk controls,
      and 24 healthy controls. PDGF-AB mean concentration was higher in PM patients
      (45.8 ng/ml) than in high-risk controls (33.1 ng/ml) and healthy controls (26.8
      ng/ml). Using the cut-off level of 49.8 ng/ml, corresponding to the mean+2SD of
      PDGF-AB in healthy controls, 43% of PM patients showed positive PDGF-AB levels.
      Survival was evaluated in 82 PM patients. At the end of the follow-up (median 9.8
      months) 80.5% of patients had died. Median survival was 13.1 and 7.9 months for
      patients with PDGF-AB lower and higher than the cut-off, respectively. Adjusting
      for age, sex, histology and platelet count, positive PDGF-AB levels were
      associated with lower survival (OR=1.2, 95%CI: 0.9-1.6), even if not
      significantly so. In conclusion, serum PDGF may represent a useful additional
      parameter to prognostic factors already available for PM.

PMID- 16103744
TI  - Identification of new splice variants and differential expression of the human
      kallikrein 10 gene, a candidate cancer biomarker.
AB  - The human kallikrein gene 10 (KLK10) is a member of the kallikrein gene family on
      chromosome 19q13.4. This gene was identified by its downregulation in breast
      cancer, and preliminary evidence suggests that it may act as a tumor suppressor.
      A computer-based analysis was performed on EST and SAGE clones from the Cancer
      Genome Anatomy Project and other databases. Experimental verification of
      differential expression of KLK10 in cancer was performed by PCR using gene
      specific primers. The mRNA and EST analysis allowed the construction of the
      longest transcript of the gene and characterization of a 5' extension of the
      reported mRNA. In addition, seven new splice variants of KLK10 were identified.
      One of these variants, named KLK10 splice variant 3 (KLK10-SV3) which starts with
      a novel first exon, was experimentally verified. This variant is predicted to
      encode for the same protein as the 'classical' KLK10 mRNA, since the first exon
      is untranslated. One variant mRNA partially matches with the sequence of KLK10,
      while the rest of the mRNA matches with a portion of the polycystic kidney
      disease gene, found on chromosome 15. This variant could not be experimentally
      verified in either normal or cancerous tissues. There are 39 reported single
      nucleotide polymorphisms (SNPs) for the gene, in which three result in amino acid
      substitutions. SAGE analysis shows a clear upregulation of KLK10 in ovarian,
      pancreatic, colon, and gastric cancers. The gene is, however, downregulated in
      breast and prostate cancers. A three-fold decrease in expression levels was noted
      in actinic keratosis, compared to normal skin from the same patient. The
      differential regulation of KLK10 in ovarian and prostate cancers was
      experimentally verified by RT-PCR analysis. In addition, a significant number of
      clones were isolated from carcinomas of the head and neck. Fewer clones were
      found in carcinomas of the skin, brain and prostate. Orthologues were identified
      in three other species, with the highest degree of homology observed with the
      mouse and rat orthologues (42% in each). In conclusion new splice variants of the
      KLK10 gene were identified. These in silico analyses show a differential
      expression of the gene in various malignancies and provide the basis for
      directing experimental efforts to investigate the possible role of the gene as a
      cancer biomarker.

PMID- 16103745
TI  - Microarray comparative genomic hybridization profile of a murine model for
      epithelial ovarian cancer reveals genomic imbalances resembling human ovarian
      carcinomas.
AB  - Microarray comparative genomic hybridization (mCGH) is emerging as a high
      resolution technology to detect gene dosage alterations in numerous pathologies,
      including cancer. We optimized cDNA microarrays to identify genome-wide
      imbalances in spontaneously transformed mouse ovarian surface epithelial cell
      lines, an in vitro murine model for ovarian cancer. Amplification of chromosome
      19 and a more variable gain pattern of chromosomes 15 and 5 were detected and
      independently validated using conventional metaphase CGH. In addition, cryptic
      aberrations in segments of chromosomes 4, 7, 8, 9, 11, 17, and X, allowed
      identification of 2 related genomic variants among six cell lines studied. Mouse
      human synteny revealed an overall early transformation stage with approximately
      80% conservation relative to human ovarian malignancies of epithelial origin
      including low malignant potential tumors, serous carcinoma, and carcinoma cell
      lines. Importantly, three of the cells bear gained segments 13 and 41 Mbp length
      of chromosomes 5 and 15, respectively, which are syntenic to human 22q11-13, 8q24
      and 12p11-q24, the two latter chromosomal regions thought to define one pathway
      of karyotypic changes in the development of human ovarian tumors. Our findings
      support the utility of mouse ovarian surface epithelial (MOSE) cells in studying
      initiation and progression of human ovarian cancer and as a suitable model to
      evaluate therapeutic approaches.

PMID- 16103746
TI  - VSGP/F-spondin: a new ovarian cancer marker.
AB  - The discovery of genes that are overexpressed in ovarian cancers provides
      valuable insight into ovarian cancer biology and will lead to the development of
      more effective treatment strategies for combating this disease. To identify genes
      exhibiting ovarian- and ovarian cancer-specific expression, we generated four
      subtracted cDNA libraries from primary and metastatic ovarian adenocarcinoma
      tissues. 3,400 cDNA clones from these libraries were analyzed by microarray for
      tissue distribution and tumor specificity using 32 pairs of fluorophore-labeled
      cDNA samples from a variety of normal tissues and ovarian tumor tissues. cDNA
      clones showing elevated expression in ovarian tumors were identified by DNA
      sequencing with comparison to public databases, and the most promising candidates
      were further analyzed by quantitative real-time polymerase chain reaction and
      Northern blot. This systematic approach led to the identification of a number of
      genes including vascular smooth muscle growth-promoting factor (VSGP/F-spondin),
      a secreted protein previously identified and cloned from bovine and human ovary.
      VSGP/F-spondin protein was observed in ovarian carcinomas but not in normal
      ovarian epithelium by immunohistochemistry with a VSGP/F-spondin antibody. The
      expression profile of VSGP/F-spondin identifies this molecule as a potential
      diagnostic marker or target for developing therapeutic strategies to treat
      ovarian carcinoma.

PMID- 16103747
TI  - Immunostimulatory CpG oligonucleotides reduce tumor burden after intravesical
      administration in an orthotopic murine bladder cancer model.
AB  - Bacillus Calmette-Guerin is established in the prophylaxis of recurrent
      intermediate and high-risk superficial bladder cancer and induces an unspecific,
      Th1-biased local immune response. Small CpG oligonucleotides (CpG ODN) containing
      a central unmethylated CpG motif are able to mimic the immunostimulatory activity
      of bacterial DNA. The purpose of the present study was to evaluate the
      antineoplastic properties of intravesically administered CpG ODN in an orthotopic
      murine bladder cancer model. MB49 tumor cell suspension was instilled
      transurethrally in female C57/BL6 mice on day 0. Mice were divided in three
      groups of 12 animals. Four mice in each group received either stimulative CpG
      ODN, non-stimulative GpC ODN or PBS intravesically: group I on day 3, group II on
      day 5, group III on day 7. After sacrifice 7 days after treatment, bladders were
      removed and histological examinations were performed. Single instillation of CpG
      ODN revealed antineoplastic effects in every group demonstrated by significantly
      lower bladder weight compared with non-stimulative GpC ODN- and PBS-treated mice.
      Histological examination showed extensive infiltration of macrophages and
      lymphocytes in CpG ODN-treated mice, whereas PBS- and GpC ODN-treated mice showed
      solid tumor growth with only few leucocytes. Intravesically applied
      immunostimulative DNA demonstrated antitumoral activity in an orthotopic murine
      bladder cancer model. A single instillation seems to be sufficient to reduce
      tumor load.

PMID- 16103748
TI  - Marine-derived cancer therapeutics making a splash.

PMID- 16103749
TI  - Importance of rational pre-clinical development: gemcitabine comes of age.

PMID- 16103750
TI  - Nucleophosmin/B23, a multifunctional protein that can regulate apoptosis.
AB  - Nucleophosmin (NPM)/B23, a multifunctional nucleolar protein, is overexpressed in
      actively proliferating cells and cancer cells. B23 is a tumor marker and exerts
      its oncogenic effect through binding and suppressing numerous tumor suppressors.
      NPM-ALK, an aberrant fusion protein produced from t(2;5) translocation in
      anaplastic large cell lymphoma (ALCL), fuses the N-terminus of B23 to the
      intracellular tyrosine kinase domain of ALK, provoking lymphomas by stimulating
      various mitogenic proteins including PI 3-kinase and PLC-gamma1. Overexpression
      of B23 inhibits apoptosis, while knockdown of B23 induces cell death. However,
      whether B23 is directly involved in blocking apoptotic machinery remains elusive.
      B23 is recently identified as a nuclear PI(3,4,5)P3 binding protein through a
      PI(3,4,5)P3 column and NGF-treated PC12 nuclear extracts. B23 has been shown to
      mediate the anti-apoptotic effects of NGF by inhibiting DNA fragmentation
      activity of CAD. B23 mutants that cannot associate with PI(3,4,5)P3 fail to
      prevent DNA fragmentation, indicating that PI(3,4,5)P3/B23 complex regulates the
      anti-apoptotic activity of NGF in the nucleus. Identification of a small molecule
      mediating the anti-apoptotic action of B23 unveils a novel therapeutic target for
      treatment of B23 amplified cancers.

PMID- 16103751
TI  - Good timing in the cell cycle for precise DNA repair by BRCA1.
AB  - It is now clear that large DNA-binding proteins have evolved in mammals to
      orchestrate the relatively ancient process of DNA recombinational repair. These
      proteins are recruited to accurately repair DNA double strand breaks (DSBs)--the
      frequent, potentially lethal and mutagenic lesions in the genomes of all
      organisms. An essential mammalian regulator of DSB repair is BRCA1. Heterozygous
      BRCA1 mutations predispose individuals to breast, ovarian and other secondary
      cancers. BRCA1-defective cells exhibit reduced DSB repair, sensitivity to a wide
      range of DNA damaging agents, genomic instability and defects in the S-phase
      checkpoint, transcription and chromatin remodelling. DSBs can be repaired by
      RAD51/RPA-dependent homologous recombination (HR) or DNA-PK-dependent non
      homologous end-joining (NHEJ). Both of these pathways can be imprecise and
      mutagenic. BRCA1 plays a central role in promoting accurate repair by both HR and
      NHEJ. Consistent with recent evidence, we have assembled a novel cell-cycle
      dependent model in which DNA-PK inhibits RPA in S-phase of the cell cycle, while
      BRCA1 inhibits the exonuclease processivity of the MRE11/RAD50/NBS1 (MRN) complex
      and facilitates the removal of RPA in S and G2 phase. This model provides an
      explanation for how BRCA1 promotes accurate DSB repair during various phases of
      the cell cycle and also accounts for the dual effects that BRCA1 and MRN activity
      have upon DNA repair and S-phase arrest.

PMID- 16103752
TI  - Activating p38 MAPK: new tricks for an old kinase.
AB  - Mitogen-activated protein kinases (MAPKs) participate in signaling initiated by a
      wide variety of extracellular stimuli. MAPKs are most commonly activated by a
      series of phosphorylation events in which one kinase phosphorylates another, the
      "MAPK cascade". The cascade concludes with the dual phosphorylation of MAPKs on a
      conserved Thr-X-Tyr motif. In the case of the p38 MAPK, an exception to this
      paradigm has been found when signaling via the T cell antigen receptor (TCR).
      Rather than trigger the MAPK cascade, TCR-mediated stimulation activates proximal
      tyrosine kinases, which results in the phosphorylation of p38 on a noncanonical
      activating residue, Tyr-323. This phosphorylation activates p38 to phosphorylate
      third party substrates as well as its own Thr-Gyl-Tyr motif. Here we discuss the
      structural and functional implications of this alternative p38 activation
      pathway, which may provide a new target for tissue-specific pharmacologic
      inhibition.

PMID- 16103753
TI  - Microtubule Associated Protein (MAP)-Tau: a novel mediator of paclitaxel
      sensitivity in vitro and in vivo.
AB  - Microtubule binding protein Tau was recently identified through gene expression
      analysis of human breast cancer tissues as a novel marker of response to
      paclitaxel. This article reviews these recent findings and provides additional
      information to support the role of Tau as an emerging marker and mediator of
      paclitaxel sensitivity. Low expression of Tau is associated with increased
      sensitivity to paclitaxel in human breast cancer as well as in a broad range of
      cell lines. Down regulation of Tau in cell lines by siRNA increases their
      sensitivity to paclitaxel but not to anthracycline chemotherapy. We propose that
      this is due to increased paclitaxel binding to microtubules when microtubules are
      assembled in the presence of low concentrations (or absence) of Tau compared to
      microtubules that are formed in the presence of physiological (or higher) levels
      of Tau.

PMID- 16103754
TI  - Comments on progress, medical care, and the overuse of technology.

PMID- 16103755
TI  - Ethnic differences in the treatment and control of hypertension in patients with
      diabetes.
AB  - Among diabetic hypertensive patients, ethnic differences in blood pressure
      control and outcomes have been attributed in part to greater reluctance of
      providers to prescribe combination antihypertensive regimens to African Americans
      than to Caucasians. African Americans purportedly receive fewer angiotensin
      converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs),
      which reduce target organ complications. To assess these issues, cross-sectional
      data were analyzed from 19,864 diabetic hypertensives from 62 primary care
      clinics. Among diabetic hypertensives, African Americans (N=6230) were less
      likely than Caucasians (N=8041) to have blood pressure (BP) <130/80 mm Hg at
      their last clinic visit (23.1% [23.0%-23.2%] vs. 30.7% [30.6%-30.9%]) despite a
      greater number of prescriptions for antihypertensive medications (2.67 [2.63
      2.70] vs. 2.23 [2.20-2.26]). African Americans were more likely than Caucasians
      to have an ACEI and/or ARB prescribed and to receive prescriptions for at least
      two antihypertensive medications that included an ACEI or ARB (64.1% [63.8%
      64.4%] vs. 53.1% [52.8%-53.4%]). Among diabetic hypertensives, African Americans
      are less likely than Caucasians to attain BP <130/80 mm Hg, despite receiving
      more antihypertensive medication prescriptions. African Americans receive more
      ACEIs and/or ARBs than Caucasians for target organ protection and/or BP control.
      The data suggest provider prescribing patterns are not a major contributor to
      ethnic differences in BP control and outcomes in diabetic hypertensives.

PMID- 16103756
TI  - Effect of diet and exercise on pulse pressure and cardiac function in morbid
      obesity: analysis of 24-hour ambulatory blood pressure.
AB  - Blood pressure is a major risk factor for cardiovascular events, although the
      role of pulse pressure, an independent predictor of arterial stiffness, has
      recently been emphasized. This study examines the baseline relationship between
      body mass index (BMI) and blood pressure indexes in 215 obese African Americans
      enrolled in a diet-exercise program. The subject population was 77% female, with
      a mean +/- SD age of 46.7+/-10.7 years and a mean BMI of 42.5+/-7.5 kg/m2. In
      addition, the authors prospectively examined the effect of weight loss on
      cardiovascular parameters in a subset of 25 participants. The results show a
      closer significant correlation between pulse pressure and BMI (b=1.97 kgm-1;
      p=0.001) than between systolic blood pressure and BMI (b=1.58 kgm-1; p=0.020).
      After 3 months of diet and exercise, average reductions were as follows: BMI, 4.2
      kg/m2 (p<0.01); systolic blood pressure, 7.2 mm Hg (p<0.01); pulse pressure, 4.8
      mm Hg (p<0.01); and cardiac output, 975 mL/min (p<0.01). Compliance index
      increased by 0.1 mL/mm Hg/m2 (p=0.03). The results highlight the potential value
      to cardiovascular health of a modest reduction in body weight in obese
      individuals.

PMID- 16103757
TI  - Treating stage 2 hypertension.
AB  - The prevalence of hypertension increases with advancing age, due primarily to
      increases in systolic blood pressure. Systolic hypertension is the most common
      form of hypertension in individuals over 50 years of age and reflects pathologic
      decreases in arterial compliance. Systolic blood pressure elevation is a more
      important risk factor for cardiovascular disease than is diastolic blood pressure
      elevation. Stage 2 hypertension, defined as blood pressure > or =160/100 mm Hg,
      is often found in older persons, who are at highest risk for cardiovascular
      events. In this clinical review, hypertension experts utilize a case study to
      provide a paradigm for treating older patients with stage 2 hypertension.

PMID- 16103758
TI  - Hypertension and the cardiometabolic syndrome.
AB  - Hypertension and cardiovascular disease are leading causes of morbidity and
      mortality. Accumulating data demonstrate a relationship between hypertension and
      several vascular and metabolic abnormalities that are components of the
      cardiometabolic syndrome. The components of the cardiometabolic syndrome include
      insulin resistance/hyperinsulinemia, central obesity, dyslipidemia, hypertension,
      microalbuminuria, increased inflammation, and oxidative stress. There is growing
      evidence that tissue activation of the renin-angiotensin-aldosterone system
      participates in endothelial dysfunction, microalbuminuria, insulin resistance,
      and subsequent cardiovascular and chronic kidney disease. The notion that
      hypertension is a metabolic as well as a vascular disease opens a new paradigm
      for the treatment of this disorder.

PMID- 16103759
TI  - Hypertension, renal disease, and cardiovascular outcomes.
AB  - During the meeting of the American Society of Hypertension in San Francisco, CA
      on May 17, 2005, a roundtable was convened to discuss the relationship between
      hypertension, renal disease, and cardiovascular outcomes. Dr. Marvin Moser,
      Clinical Professor at Yale University School of Medicine, New Haven, CT, chaired
      the session. Dr. Jan Basile, Professor of Medicine at the Ralph Johnson VA
      Medical Center and the Medical University of South Carolina in Charleston, SC and
      Dr. William Cushman, Professor of Preventive Medicine and Medicine at the
      University of Tennessee in Memphis, TN participated in the discussion.

PMID- 16103760
TI  - Pharmacotherapy review: angiotensin-converting enzyme inhibitors.
AB  - On inspection of most treatment algorithms for hypertension, it is apparent that
      multiple drug classes are available. In choosing a medication class for
      hypertension therapy, nuances of the selection process often go unappreciated.
      This article is the first in a series describing important pharmacotherapeutic
      considerations of the individual drug classes used in the treatment of
      hypertension.

PMID- 16103761
TI  - Analysis of recent papers in hypertension. An angiotensin receptor blocker is
      more effective than a calcium channel blocker in secondary stroke prevention.

PMID- 16103762
TI  - Lessons learned.

PMID- 16103763
TI  - Cost effectiveness and delivery study for future HIV vaccines.
AB  - Research teams from five countries, Brazil, China, Kenya, Peru and Thailand, have
      initiated a policy-maker survey on vaccine delivery, cost studies for future HIV
      vaccination programmes, and associated simulation modeling exercises analysing
      the relative cost-effectiveness of potential HIV vaccination strategies. The
      survey assesses challenges and opportunities for future country-level HIV
      vaccination strategies, providing data on the vaccine characteristics (e.g.
      vaccine efficacies for susceptibility, infectiousness and disease progression)
      and vaccination programme strategies to be considered in the cost-effectiveness
      modeling analyses. The study will provide decision-makers with modeling data on
      vaccination policy considerations that will assist in developing country-level
      capacities for future HIV vaccine policy adoption and effective delivery systems,
      and will help delineate the long-term financial requirements for sustainable HIV
      vaccination programmes. The WHO-UNAIDS HIV Vaccine Initiative and the
      collaborating researchers welcome comments or questions from policy makers,
      health professionals and other stakeholders in the public and private sectors
      about this effort to help advance policy and capacity related to future potential
      HIV vaccines.

PMID- 16103764
TI  - Mitochondrial haplogroups and peripheral neuropathy during antiretroviral
      therapy: an adult AIDS clinical trials group study.
AB  - OBJECTIVE: HIV nucleoside reverse transcriptase inhibitors (NRTI) can cause
      peripheral neuropathy that is a result of mitochondrial injury. Polymorphisms in
      the mitochondrial genome define haplogroups that may have functional
      implications. The objective of this study was to determine if NRTI-associated
      peripheral neuropathy is associated with European mitochondrial haplogroups.
      DESIGN: Case-control study of Adult AIDS Clinical Trials Group (ACTG) study 384
      and ACTG Human DNA Repository participants. METHODS: ACTG study 384 was a
      treatment strategy trial of antiretroviral therapy with didanosine (ddI) plus
      stavudine (d4T) or zidovudine plus lamivudine given with efavirenz, nelfinavir,
      or both. Subjects were followed for up to 3 years. Peripheral neuropathy was
      ascertained based on signs and symptoms. For this analysis, polymorphisms that
      define European mitochondrial haplogroups were characterized in a majority of
      ACTG 384 participants, and associations with peripheral neuropathy were assessed
      using logistic regression. RESULTS: A total of 509 subjects were included in this
      analysis of whom 250 (49%) were self-identified as white, non-Hispanic.
      Mitochondrial haplogroup T was more frequent in subjects who developed peripheral
      neuropathy. Among 137 white subjects randomized to receive ddI plus d4T, 20.8% of
      those who developed peripheral neuropathy belonged to mitochondrial haplogroup T
      compared to 4.5% of control subjects (odds ratio, 5.4; 95% confidence interval,
      1.4-25.1; P = 0.009). Independent predictors of peripheral neuropathy were
      randomization to receive ddI plus d4T, older age, and mitochondrial haplogroup T.
      CONCLUSIONS: A common European mitochondrial haplogroup may predict NRTI
      associated peripheral neuropathy. Future studies should validate this
      relationship, and evaluate non-European mitochondrial haplogroups and other NRTI
      toxicities.

PMID- 16103765
TI  - Enrichment of activated monocytes in cerebrospinal fluid during antiretroviral
      therapy.
AB  - OBJECTIVES: In HIV infection, activated monocytes are enriched in blood and in
      the perivascular area of the brain, especially in patients with HIV-associated
      dementia. Although clinical brain disease is uncommon during combination
      antiretroviral therapy (ART), autopsy series indicate that HIV-infected brain
      tissue can contain high numbers of monocytes/macrophages despite ART. DESIGN: We
      assessed activated monocytes in blood and cerebrospinal fluid (CSF) in 76 living
      patients on and off ART. Plasma lipids were measured because they have been
      associated with monocyte activation and ART. METHODS: A novel quantitative six
      color flow cytometric approach was used to identify monocytes in blood and CSF
      and to evaluate monocyte activation status. RESULTS: The mean percentage and
      number of activated CD16 monocytes in CSF was highest in individuals on
      combination ART, especially in those receiving protease inhibitors (PI). CSF
      viral load was also associated with higher monocyte activation in CSF. The mean
      calculated low density lipoprotein (LDL)-, oxidized LDL- and total cholesterol in
      plasma were highest in patients receiving PI. CONCLUSIONS: Activated monocytes
      are enriched in the CSF of persons living with HIV-1 and receiving ART. This
      finding is consistent with previously reported autopsy series. The mechanisms and
      long-term clinical consequences of persistent monocyte activation require further
      study.

PMID- 16103766
TI  - Single (B or C), dual (BC or BD) and triple (BCD) viral hepatitis in HIV-infected
      patients in Madrid, Spain.
AB  - INTRODUCTION: There are very limited data about the prevalence of multiple
      hepatitis virus infections in HIV infected individuals. In HIV uninfected
      individuals with triple BCD hepatitis, hepatitis D virus (HDV) appears to be the
      dominant virus. However, in HIV infected patients with triple hepatitis it is not
      known if HDV replication inhibits hepatitis B virus (HBV) and/or hepatitis C
      virus (HCV) replication. METHODS: We calculated the prevalence of single (B or
      C), dual (BC) and triple (BCD) hepatitis in 423 HIV-infected patients with
      positive HCV serum antibodies and/or positive serum HBsAg. In patients with
      multiple infections we performed an evaluation of serum markers of HBV, HCV and
      HDV replication. RESULTS: The prevalence of multiple hepatitis was 4.7% (95%
      confidence interval, 2.7-6.7%). Multiple hepatitis occurred only among patients
      who acquired HIV through injection drug use. The most common multiple hepatitis
      was triple BCD. Patients with hepatitis BC and past or chronic hepatitis D were
      significantly more likely to have cirrhosis and a negative serum HBeAg and HCV
      PCR than patients with single hepatitis B or hepatitis C. Patients with chronic
      hepatitis D showed uniform suppression of HBV and HCV replication markers.
      CONCLUSIONS: In our geographic area approximately 5% of HIV infected patients
      with hepatitis suffer multiple hepatitis virus infection. In patients with triple
      hepatitis BCD virus infection, HDV appears to be the dominant virus causing
      inhibition of both HBV and HCV replication.

PMID- 16103767
TI  - The International HIV Dementia Scale: a new rapid screening test for HIV
      dementia.
AB  - OBJECTIVE: HIV dementia is an important neurological complication of advanced HIV
      infection. The use of a cross-cultural screening test to detect HIV dementia
      within the international community is critical for diagnosing this condition. The
      objective of this study was to evaluate the sensitivity and specificity of a new
      screening test for HIV dementia, the International HIV Dementia Scale (IHDS) in
      cohorts from the US and Uganda. DESIGN: Two cross-sectional cohort studies
      designed to evaluate for the presence of HIV dementia. METHODS: Sixty-six HIV
      positive individuals in the US and 81 HIV-positive individuals in Uganda received
      the IHDS and full standardized neurological and neuropsychological assessments.
      The sensitivity and specificity of varying cut-off scores of the IHDS were
      evaluated in the two cohorts. RESULTS: In the US cohort, the mean IHDS score for
      HIV-positive individuals without dementia and with dementia were 10.6 and 9.3
      respectively (P < 0.001). Using the cut-off of < or = 10, the sensitivity and
      specificity for HIV dementia with the IHDS were 80% and 57% respectively in the
      US cohort, and 80% and 55% respectively in the Uganda cohort. CONCLUSIONS: The
      IHDS may be a useful screening test to identify individuals at risk for HIV
      dementia in both the industrialized world and the developing world. Full
      neuropsychological testing should then be performed to confirm a diagnosis of HIV
      dementia.

PMID- 16103768
TI  - Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is
      associated with insulin resistance markers in the Multicenter AIDS Cohort Study.
AB  - OBJECTIVE: To estimate insulin resistance and its relationship to antiretroviral
      therapy (ART) in a cohort of HIV-infected persons with comparison to HIV
      seronegative controls. DESIGN: Prospective cohort of 533 HIV-infected and 755 HIV
      seronegative men in the Multicenter AIDS Cohort Study evaluated at 6-month
      intervals between 1999 and 2003. METHODS: Recent ART exposure was assessed by
      type of treatment in the preceding 6 months [i.e., no ART, monotherapy,
      combination ART, or highly active antiretroviral therapy (HAART) with and without
      a protease inhibitor (PI)]. Cumulative exposure was determined for the three
      major ART classes and for individual medications within each class. Two
      endpoints, a modified QUICKI index, 100 x 1/[log10(glucose) + log10(insulin)] and
      fasting hyperinsulinemia (insulin > 15 microU/ml), were assessed. All statistical
      models were adjusted for age, body mass index, race, nadir CD4 cell count,
      hepatitis C serostatus and family history of diabetes mellitus. RESULTS: Each of
      the HIV-infected groups had higher odds of hyperinsulinemia and lower mean QUICKI
      than the HIV-seronegative men. Each additional year of exposure to nucleoside
      analogue reverse transcriptase inhibitors (NRTI) was associated with increased
      odds of hyperinsulinemia [odds ratio (OR), 1.08; 95% confidence interval (CI),
      1.02-1.13) and a lower QUICKI (-0.04; 95% CI, -0.07 to -0.01). Cumulative
      exposure to non-nucleoside analogue reverse transcriptase inhibitors or PI drugs
      was not associated with either insulin resistance marker. Of individual
      medications examined, stavudine was associated with the highest risk of
      hyperinsulinemia (OR, 1.2; 95% CI, 1.2-1.3). CONCLUSIONS: Fasting surrogate
      markers suggest increased insulin resistance in HIV-infected men, which is
      related to cumulative NRTI exposure.

PMID- 16103769
TI  - Genotypic and phenotypic resistance patterns at virological failure in a
      simplification trial with nevirapine, efavirenz or abacavir.
AB  - BACKGROUND: The NEFA Study was a randomized study comparing nevirapine (NVP),
      efavirenz (EFV) or abacavir (ABC) as substitutes for protease inhibitors in a
      large group of HIV-1-infected patients successfully treated with antiretroviral
      regimens containing protease inhibitors. OBJECTIVE: To evaluate genotype and
      phenotype resistance patterns among patients who have experienced virological
      failure under one of the three study arms. METHODS: Patients with virological
      failure, defined as two consecutive determinations of HIV-1 RNA > 200 copies/ml,
      were analysed for phenotypic susceptibility and HIV-1 mutations. RESULTS: Of the
      460 patients included in the study, 51 (11%) experienced virological failure
      after 24 months of follow-up while on assigned study medication. A higher
      proportion of patients in the ABC [25 (17%)] than in the NVP [14 (9%)] or EFV [12
      (8%)] arms selected resistance to the study drug (P = 0.04). Moreover, a much
      higher number of resistance mutations to one or more of the backbone nucleoside
      reverse transcriptase inhibitor drugs contained in the failing regimen were
      observed in the ABC than in the EFV or NVP arms. In general, there was a good
      concordance among genotype and phenotype resistance testing, except for ABC,
      stavudine and didanosine, where phenotypic resistance testing added valuable
      information (fold change in the median inhibitory concentration). CONCLUSIONS:
      Cross-resistance involving nucleoside reverse transcriptase inhibitor drugs might
      explain the higher risk of virological failure in patients switched to ABC
      containing antiretroviral therapy. Phenotypic resistance testing may be helpful
      in interpreting unclear genotypic results.

PMID- 16103770
TI  - The normalized inhibitory quotient of boosted protease inhibitors is predictive
      of viral load response in treatment-experienced HIV-1-infected individuals.
AB  - OBJECTIVE: The normalized inhibitory quotient (NIQ) has been proposed as a
      measure for refining the precision of HIV resistance testing when selecting
      antiretroviral therapy (ART). We undertook an assessment of NIQ and 48-week
      virological outcome in patients commencing ritonavir-boosted protease inhibitor
      (PI) regimens. DESIGN: A cohort of 87 HIV-infected individuals who all had
      extensive prior exposure to ART were assigned a new boosted PI regimen following
      resistance testing. PI therapy consisted of lopinavir, indinavir, saquinavir and
      amprenavir at 50, 32, 11 and 6%, respectively. Fold change (FC) for each PI was
      determined from the resistance test at baseline. Trough drug concentration (Cmin)
      was determined at week 4. METHODS: NIQ was derived individually by taking the
      logarithm of the ratio of Cmin/FC divided by the fixed ratio of population mean
      trough drug concentration/clinical cut off. Associations between viral load (VL)
      response over 48 weeks with baseline VL, FC, Cmin, NIQ and selected PI were
      assessed. RESULTS: Mean change from baseline VL reduced by 0.83 log at week 48.
      In multivariate analyses, baseline VL and NIQ were the parameters most associated
      with change from baseline VL at week 48 (P = 0.012 and 0.003, respectively). FC,
      Cmin and selected PI were not significantly associated with VL changes.
      CONCLUSION: In this cohort of highly treatment-experienced individuals treated
      with boosted PI regimens, baseline VL and NIQ were significantly predictive of
      virological response over 48 weeks whereas FC and Cmin were not. These results
      support the use of a NIQ at week 4, as a tool for predicting response to therapy
      in this setting.

PMID- 16103771
TI  - Effect of naturally-occurring gp41 HR1 variations on susceptibility of HIV-1 to
      fusion inhibitors.
AB  - BACKGROUND: Sequence variations in the gp41 heptad repeat 1 (HR1) region have
      been identified in some treatment-naive HIV-1-infected patients but it remained
      elusive whether they confer resistance to fusion inhibitors. OBJECTIVE: To
      evaluate whether naturally occurring sequence variations in the HIV-1 group M
      gp41 HR1 region affect the sensitivity to inhibition by T-20 and T-1249. METHODS:
      Site-directed mutagenesis was used to generate HIV-1 NL4-3 mutants containing
      changes in the gp41 HR1 domain which have been previously identified in treatment
      naive patients infected with various HIV-1 group M subtypes. HIV-1 variants were
      produced by transient transfection of 293T cells and used to determine viral
      infectivity and sensitivity to the fusion inhibitors T-20 and T-1249. RESULTS:
      Most naturally occurring sequence variations in the HR1 domain did not reduce
      viral infectivity. Three of the 10 HIV-1 variants analysed containing a single
      substitution of L33V, which is frequently present in subtype D isolates, or
      combined changes of L54M/Q56K or L34M/L54M/Q56R showed about fivefold reduced
      sensitivity to inhibition by T-20. In comparison, none of these HR1 sequence
      variations conferred resistance to T-1249. CONCLUSION: Some naturally occurring
      sequence variations in the gp41 HR1 region reduce sensitivity of HIV-1 to
      inhibition by T-20 but not T-1249.

PMID- 16103772
TI  - Anal intraepithelial neoplasia in the highly active antiretroviral therapy era
      among HIV-positive men who have sex with men.
AB  - OBJECTIVES: The incidence of anal cancer among men who have sex with men (MSM)
      has continued to increase since the introduction of highly active antiretroviral
      therapy (HAART). The prevalence of the putative anal cancer precursor, anal
      intraepithelial neoplasia (AIN) was high among HIV-positive MSM prior to the
      availability of HAART but little is known about AIN since HAART was introduced.
      We characterized the prevalence of AIN among HIV-positive MSM and examined the
      association between AIN and various factors including use of HAART. DESIGN AND
      METHODS: A baseline point-prevalence analyses in a prospective cohort study of
      AIN was performed at a university-based research clinic. A total of 357 HIV
      positive MSM with no history of anal cancer completed a questionnaire detailing
      behaviors and medical history, anal cytology and human papillomavirus (HPV)
      testing, and high-resolution anoscopy with biopsy for detection of AIN. RESULTS:
      Eighty-one percent of participants with available CD4+ cell counts at baseline
      had AIN of any grade; 52% had AIN 2 or 3; and 95% had anal HPV infection. In
      multivariate analysis, detection of > or = 6 HPV types [odds ratio (OR), 36; 95%
      confidence interval (CI), 7.4-171) and use of HAART (OR, 10; 95% CI, 2.6-38) were
      associated with AIN after adjustment for length of time participants were HIV
      positive, CD4+ cell count and HIV viral load. CONCLUSIONS: The prevalence of AIN
      has remained high among HIV-positive MSM after the introduction of HAART. Our
      data indicate that HAART is not associated with a reduced prevalence of AIN and
      support measures to prevent anal cancer among HIV-positive MSM whether or not
      they are using HAART.

PMID- 16103773
TI  - Breast milk HIV-1 suppression and decreased transmission: a randomized trial
      comparing HIVNET 012 nevirapine versus short-course zidovudine.
AB  - OBJECTIVE: To compare the effect of perinatal regimens of short-course nevirapine
      (HIVNET 012) and zidovudine [Thai-Centers for Disease Control and Prevention
      (CDC) regimen] on breast milk viral shedding and perinatal transmission during
      the first 6 weeks postpartum in a randomized clinical trial. DESIGN: Randomized
      clinical trial. METHODS: Pregnant HIV-1 seropositive women in Nairobi, Kenya who
      planned to breastfeed were randomized to HIVNET 012 or Thai-CDC regimens. Two to
      four breast milk samples were collected each week between delivery and 6 weeks
      postpartum. Breast milk HIV-1 RNA was quantified using the Gen-Probe TMA assay.
      Infants were tested for HIV-1 DNA at birth and 6 weeks. RESULTS: From March to
      October 2003, 76 women were enrolled and 795 breast milk samples were collected
      from 60 women who were randomized and followed after delivery. Between 3 and 21
      days postpartum, nevirapine was associated with significantly greater suppression
      of breast milk log10 HIV-1 RNA: days 3 to 7 (1.98 versus 2.42, P = 0.1); days 8
      to 14 (1.78 versus 2.48, P = 0.005); days 15 to 21 (1.90 versus 2.97, P = 0.003).
      At 6 weeks, the HIV-1 perinatal transmission rate was significantly lower among
      those who took nevirapine than zidovudine (6.8% versus 30.3%, P = 0.02).
      CONCLUSIONS: Compared to a peripartum zidovudine regimen, nevirapine was
      significantly more likely to decrease HIV-1 RNA in breast milk during the first
      week and through the third week postpartum following single-dose administration,
      and corresponded with decreased transmission risk at 6 weeks. Sustained breast
      milk HIV-1 suppression may contribute to the ability of nevirapine to decrease
      perinatal transmission of HIV-1.

PMID- 16103774
TI  - Amphetamine use is associated with increased HIV incidence among men who have sex
      with men in San Francisco.
AB  - We examined the association between amphetamine use and HIV incidence for 2991
      men who have sex with men (MSM) who tested anonymously for HIV in San Francisco.
      HIV incidence among 290 amphetamine users was 6.3% per year (95% CI 1.9-10.6%),
      compared with 2.1% per year (95% CI 1.3-2.9%) among 2701 non-users (RR 3.0, 95%
      CI 1.4-6.5). HIV prevention programmes in San Francisco should include efforts to
      reduce amphetamine use and associated high-risk sexual behaviors.

PMID- 16103775
TI  - HIV-1 chemokine co-receptor CCR5 is expressed on the surface of human
      spermatozoa.
AB  - Viruses adhering to the sperm surface are described in the semen of HIV-1
      infected individuals, although viral adhesion mechanisms have yet to be fully
      understood. We demonstrate, by cytometric analysis and immunofluorescence
      microscopy, the presence of beta-chemokine receptor 5 (CCR5) on the periacrosomal
      region of ejaculated spermatozoa. CCR5 expressed on the sperm cell surface may
      allow sperm to act as virion cellular carriers during the sexual transmission of
      HIV-1 infection.

PMID- 16103776
TI  - Identification of unique B/C recombinant strains of HIV-1 in the southern state
      of Karnataka, India.
AB  - We characterized the molecular nature of a large number of primary HIV-1 isolates
      in the four southern states of India. In addition to confirming a predominance of
      subtype C infection, for the first time we identified three B/C recombinant
      viruses in a subset of 115 samples. Unexpectedly, env sequences of two of the
      three B/C recombinants phylogenetically clustered with subtype B strains of the
      USA. The determination of the real incidence of the recombinant viruses is of
      importance.

PMID- 16103777
TI  - Increased HIV incidence among men who have sex with men in Rome.
AB  - Among 976 men who have sex with men (MSM) who had undergone repeat HIV testing
      between 1984 and 2003 at a sexually transmitted infection clinic in Rome, Italy,
      we observed a dramatic increase in HIV incidence in 2002 and 2003, with the
      cumulative incidence for 2000-2003 being twice as high as that for 1984-1995, and
      significantly higher than that for 1996-1999. This trend suggests the need for
      interventions aimed at encouraging behavioural changes among MSM.

PMID- 16103778
TI  - Concealment of HIV and unsafe sex with steady partner is extremely infrequent.

PMID- 16103779
TI  - Low incidence of hepatotoxicity in a cohort of HIV patients treated with
      lopinavir/ritonavir.
AB  - We describe the hepatotoxicity encountered in a cohort of HIV-positive patients
      treated with lopinavir/ritonavir. We used the database from the SCOLTA project,
      an on-line pharmacovigilance programme involving 25 Italian infectious disease
      centres. A total of 755 patients were followed, over a mean observation period of
      16 months. The incidence of severe events was low despite the high prevalence of
      patients co-infected with hepatitis virus at enrollment.

PMID- 16103780
TI  - Premature sister chromatid separation in HIV-1-infected peripheral blood
      lymphocytes.
AB  - To investigate the mechanism of aneuploidy that is frequently observed in AIDS,
      we examined premature sister chromatid separation (PCS), a sign of genomic
      instability, in peripheral blood cells of HIV-1-infected individuals. PCS was
      found in all six HIV-1 individuals at a high incidence. When peripheral blood
      cells from healthy volunteers were infected with HIV-1 in vitro, the incidence of
      PCS increased. This suggests that HIV-1 infection causes PCS and has the
      potential to induce aneuploidy.

PMID- 16103781
TI  - Antiretroviral resistance among HIV-positive pregnant women who have
      antiretroviral experience from previous pregnancy.

PMID- 16103782
TI  - Unexpected improvement of sexual dysfunction during atazanavir therapy.

PMID- 16103783
TI  - Hepatic steatosis with stavudine in HIV/hepatitis C virus co-infection.

PMID- 16103784
TI  - Prevalence of cardiovascular risk factors in schoolchildren in a rural Georgia
      community.
AB  - BACKGROUND: In the context of a national childhood obesity epidemic, this study
      sought to document the cardiovascular risk status of children in a rural Georgia
      community. METHODS: Anthropometrics and blood pressure were measured in 211
      children, and fasting glucose and lipid profile in 160, recruited from schools in
      2002 (grades 2 to 11, ages 7 to 18 years). RESULTS: Nearly half the
      schoolchildren (48%) were overweight or at risk of overweight; 15% had metabolic
      syndrome. Overweight children were at higher risk for metabolic syndrome and had
      more risk factors. Blood pressure: 19% had elevated systolic blood pressure; 4%
      had elevated diastolic blood pressure. Glycemia: 14% had impaired fasting glucose
      levels; no diabetes cases were detected. Lipid profile: 26% had high total
      cholesterol (>170 mg/dL), 20% had high low-density lipoprotein (>110 mg/dL), 13%
      had high triglycerides (>150 mg/dL), 43% had low high-density lipoprotein
      (females, <50 mg/dL; males, <40 mg/dL). Ethnicity, gender, and grade level were
      not predictive of risk except that fewer black children had low high-density
      lipoprotein, and blood pressure and body mass index increased with grade, as
      expected. CONCLUSIONS: Results from this study indicate a significant problem
      with overweight and cardiovascular risk in rural schoolchildren. Notably, younger
      children were just as likely to have risk factors as adolescents, suggesting that
      screening and intervention ought to begin by school age. Ethnic and gender
      differences in prevalence were not found, suggesting that contextual factors in a
      rural setting may outweigh demographic influences on risk.

PMID- 16103785
TI  - Impact of mandatory inpatient infectious disease consultation on outpatient
      parenteral antibiotic therapy.
AB  - BACKGROUND: Outpatient parenteral antibiotic therapy (OPAT) has had an important
      impact on infections historically requiring prolonged intravenous antibiotic
      treatment. Within the past decade, new antibiotics with oral/intravenous
      bioequivalence, plus recent data on infection management, have increased the
      potential role of the Infectious Disease (ID) consultant for OPAT. METHODS: We
      studied the impact of mandatory ID consultation on the use and outcomes of OPAT
      in patients initially hospitalized. The study was approved by the Institutional
      Review Board and the Executive Committee of the Medical Staff of Baystate Medical
      Center. Patients older than 18 years of age being considered for discharge to
      home on OPAT were identified, primarily through discharge planning. Formal ID
      consultation was performed to determine both need for OPAT and a variety of
      issues regarding antibiotic choice. Thirty-day telephone follow-up determined
      outcomes. Data regarding demographics, outcomes, and costs were analyzed.
      RESULTS: Forty-four patients received mandatory ID consultation, 39 (88.6%) of
      whom had some change in antibiotic recommendations. Seventeen (38.6%) were
      discharged on oral antibiotics, 1 (2.3%) had antibiotics discontinued, 13 (29.6%)
      had a change in parenteral antibiotic, 5 (11.4%) had a change in antibiotic dose,
      and 3 (6.8%) had a change in antibiotic duration. Follow-up demonstrated a single
      rehospitalization for unrelated issues. The total cost savings were 33,667.00 US
      dollars, approximately 760.00 US dollars per patient. Charges of consults were
      approximately 11,970.00 US dollars, still resulting in savings of close to
      21,700.00 US dollars, or almost 500.00 US dollars per patient. CONCLUSIONS:
      Mandatory ID consultation resulted in substantial cost savings and excellent
      outcomes.

PMID- 16103786
TI  - Vancomycin-tolerance among clinical isolates of Streptococcus pneumoniae in
      Mississippi during 1999-2001.
AB  - BACKGROUND: In recent years, infection with Streptococcus pneumoniae has been a
      serious worldwide health concern. Antimicrobial-resistant S pneumoniae is
      increasing in incidence worldwide, posing a potentially serious threat.
      Resistance to beta-lactams, macrolides, and trimethoprim-sulfamethoxazole
      represents a major problem in the treatment of pneumococcal infections METHODS:
      Our laboratory conducted a survey of local resistance patterns in S pneumoniae.
      Clinical isolates from two separate respiratory seasons were collected from
      representative geographic areas in Mississippi (totaling 28 hospitals) and were
      tested for antimicrobial resistance to penicillin, amoxicillin, ceftriaxone,
      cefuroxime, azithromycin, clindamycin, tetracycline, trimethoprim
      sulfamethoxazole, levofloxacin, gatifloxacin, moxifloxacin, and vancomycin using
      reference methods. Vancomycin-tolerant strains of S pneumoniae were initially
      identified as those in which the vancomycin MIC was 0.5 microg/mL. Strain
      tolerance was confirmed by time kill studies RESULTS: For the 1999-2000
      respiratory season, 318 isolates were available for testing; for 2001-2002, 166
      isolates were available. Of the 484 total isolates tested, two isolates were
      identified as having increased tolerance to vancomycin. A greater than 2 log10
      difference in viability between the tolerant isolates and the nontolerant
      isolates of S pneumoniae was observed in time kill studies CONCLUSIONS: Two
      vancomycin-tolerant isolates of S pneumoniae were identified and characterized.
      Antibiotic tolerance is defined as the ability of bacteria to survive but not
      proliferate in the presence of an antibacterial agent. Tolerance to vancomycin is
      particularly significant when the incidence of penicillin tolerance or resistance
      is high. In addition, tolerance to vancomycin is not detected by routine in vitro
      susceptibility testing.

PMID- 16103787
TI  - The role of statins in chronic kidney disease.
AB  - Chronic kidney disease is associated with cardiovascular event rates that are at
      least as high as in patients with established atherosclerotic cardiovascular
      disease or in those with diabetes mellitus. Chronic kidney disease is therefore
      considered a cardiovascular disease risk equivalent. Treatment of dyslipidemia,
      which is very common in this population and reflects the pattern seen in the
      metabolic syndrome, reduces cardiovascular events in patients with chronic kidney
      disease. Thus, patients with chronic kidney disease should be evaluated and
      treated for dyslipidemia. Dyslipidemia is a risk factor for the development of
      impaired kidney function. Dyslipidemia is also associated with progressive renal
      disease in subjects with no overt renal disease, as well as those with diabetic
      and nondiabetic kidney disease. Although definitive randomized controlled trials
      are lacking, the collective evidence suggests that treatment of dyslipidemia is
      associated with less decline in renal function. The use of potent statins in high
      doses can lead to transient proteinuria via impairment of proximal tubular
      receptor--mediated endocytosis, in a dose-dependent manner. Over the long term,
      however, the use of statins results in a reduction in proteinuria and in the rate
      of decline of renal function. Several large definitive trials that are currently
      underway to examine the safety and efficacy of statins in cardiovascular and
      renal protection should provide more definitive answers on the role of these
      drugs in this very high risk population.

PMID- 16103788
TI  - Inferior vena caval filters: key considerations.
AB  - Surgical interruption of the inferior vena cava (IVC) as a means to prevent
      pulmonary embolism and its consequences has been entertained since the end of the
      19th century. Initial methods were crude, however, but their deficiencies led to
      the development of newer techniques. Despite increasing indications and use of
      permanent IVC filters there remains controversy regarding their efficacy and
      complications. The purpose of this article is to review the pertinent literature
      and, it is hoped, aid in the development of a rational approach to the use of IVC
      filters. The evolving data regarding the retrievable filters are also discussed.

PMID- 16103789
TI  - Alternative therapies for orthotopic heart transplantation.
AB  - Heart failure has reached epidemic proportions in the United States. More than 5
      million patients are treated for heart failure and approximately a half a million
      new patients are diagnosed with this disease each year in the United States.
      Recent pharmacological therapies have been used for the treatment of this patient
      population, but heart failure remains a major source of morbidity and mortality
      for patients. Orthotopic heart transplantation is a viable treatment option for
      heart failure patients; however, cardiac transplantation is limited by the donor
      availability. Limited donor organ availability has led to the development of
      alternative therapeutic strategies, including xenotransplantation, mechanical
      support devices, and cell transfer/tissue engineering protocols. This review
      highlights the current treatment modalities and emerging strategies for the
      treatment of advanced heart failure.

PMID- 16103790
TI  - Clinical characteristics of linezolid-resistant Staphylococcus aureus infections.
AB  - Case reports have previously identified linezolid resistance in 6 clinical
      isolates of Staphylococcus aureus. We describe an additional case and discuss
      clinical characteristics of these patients. Invasive procedures, deep organ
      involvement, and presence of foreign material were predominant in these cases.
      Resistance followed prolonged (>21 days) linezolid therapy in most cases. The
      development of resistance to linezolid should be taken into account when
      selecting this drug as a therapeutic option.

PMID- 16103791
TI  - Get to know your QIO: an exemplar: Pennsylvania QIO develops program on improving
      medication management.

PMID- 16103793
TI  - Readers respond to loss of home care nursing certification.

PMID- 16103796
TI  - Readers respond to loss of home care nursing certification.

PMID- 16103797
TI  - Compliance with the Medicare conditions of participation: patient rights.

PMID- 16103798
TI  - Inappropriate drug prescriptions for older adults.

PMID- 16103799
TI  - Living OASIS: then and now.

PMID- 16103800
TI  - The art of skin and wound care documentation.
AB  - PURPOSE: To provide physicians and nurses with an overview of strategies for
      descriptive documentation of skin and wound assessments and interventions. TARGET
      AUDIENCE: This continuing education activity is intended for physicians and
      nurses with an interest in learning about strategies for documenting skin and
      wound assessments and interventions. OBJECTIVES: After reading the article and
      taking the test, the participant will be able to: 1. Describe documentation
      related to the use of risk assessment and manual assessment tools. 2. Describe
      documentation related to the use of skin and wound assessment tools.

PMID- 16103802
TI  - Introducing reflective narratives into palliative care home care education.
AB  - The purpose of the research project was to determine the impact of palliative
      care education and the writing of a reflective narrative on nurses' self
      awareness of their attitudes toward death and care of the dying. Findings support
      integration of narrative reflection into palliative care education as an
      effective teaching strategy.Only qualitative findings of a larger study are
      presented; quantitative results have been published in the Journal of Hospice &
      Palliative Nursing (Home care and hospice nurses' attitudes toward death and
      caring for the dying: effects of palliative care education. 2005;7[4], 212-218).

PMID- 16103803
TI  - Promoting physiologic-physical adaptation in chronic obstructive pulmonary
      disease: pharmacotherapeutic evidence-based research and guidelines.
AB  - Guidelines from the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      and evidence-based research include advanced pharmacologic care for patients with
      chronic obstructive pulmonary disease (COPD). Although clinical trials of
      medications have not supported evidence that long-term decline in pulmonary
      function can be prevented, pharmacologic agents can reduce symptoms and prevent
      complications. High-quality home care services may improve quality of life and
      prevent hospital admissions because of acute exacerbations.

PMID- 16103805
TI  - Ask Home Healthcare Nurse.

PMID- 16103806
TI  - VNAA CHAMP program to measure and raise quality of geriatric home care for all
      agencies.

PMID- 16103808
TI  - "Everything I know I learned from home care nurses": a social worker reflects.

PMID- 16103809
TI  - The promise of MAPP: a transformational tool for public health practice.

PMID- 16103810
TI  - MAPP and the evolution of planning in public health practice.
AB  - Mobilizing for Action through Planning and Partnerships, the most recent planning
      tool in public health practice, is built upon a long history of planning by local
      public health agencies (LPHAs). Planning by LPHAs has evolved over half a century
      from the earliest problem/program-focused planning, through more comprehensive
      approaches like the Planned Approach to Community Health (PATCH) and the
      Assessment Protocol for Excellence in Public Health (APEXPH) to strategic
      planning of today. While LPHAs were not notably participants in the federally
      sponsored health planning of the 1960s and 1970s, this planning left a legacy in
      public health. Mobilizing for Action through Planning and Partnerships introduces
      strategic thinking and a systems orientation into public health planning that
      builds upon this legacy.

PMID- 16103811
TI  - Developing the MAPP community health improvement tool.
AB  - From 1997 to 2001, the National Association of County and City Health Officials,
      in collaboration with the Centers for Disease Control and Prevention's Public
      Health Practice Program Office, developed a new community strategic planning
      tool, titled Mobilizing for Action through Planning and Partnerships (MAPP). This
      article provides a chronological description of the development of MAPP, devoting
      significant attention to pivotal decisions, development milestones, and
      distinguishing features of this new public health planning tool. All phases of
      the development ensured a practice-driven process, ongoing substantive input from
      the field, careful attention to research and literature, and intentional linkage
      with related efforts. This deliberate process laid the foundation for a tool that
      is not only well grounded in research and concepts but also relevant for
      practical use in communities. The process also demonstrates how practice-based
      research can be conducted in a way that effectively balances the need for applied
      relevance with intellectual integrity.

PMID- 16103812
TI  - MAPP in Chicago: a model for public health systems development and community
      building.
AB  - The Chicago Department of Public Health's (CDPH's) community planning efforts
      came from a city-wide strategic plan that called for the establishment of a city
      wide network of community partnerships that focus on community needs and resource
      assessment and program development. Using Mobilizing for Action through Planning
      and Partnerships as a framework for planning at the community level, the CDPH
      supports five community coalitions through the Chicago Center for Community
      Partnerships. The overall goal of the Center is to increase community capacity,
      build new partnerships, provide coalitions with access to decision makers, and
      inform the role of local public health agencies in supporting this type of work.
      Bringing together a wide spectrum of stakeholders, coalition members work to
      conduct assessments and develop and implement strategies. While coalitions
      demonstrate outcomes related to specific strategies, they also exhibit
      infrastructure-level results, with increased levels of community organizing,
      leveraging of existing resources, and new systems for information dissemination.
      Simultaneously, the CDPH has gained new partners in public health, increased
      collaboration, and more information about communities. These outcomes are
      contingent on certain elements of success: (1) committed leadership; (2)
      commitment to a new way of doing business; (3) prepared public health workforces;
      and (4) community readiness.

PMID- 16103813
TI  - Integrating MAPP, APEXPH, PACE-EH, and other planning initiatives in Northern
      Kentucky.
AB  - Northern Kentucky is the first NACCHO demonstration site in the nation to utilize
      the Mobilizing for Action through Planning and Partnerships (MAPP) tool as one
      element in the development of a comprehensive community health plan. The Northern
      Kentucky Independent District Health Department utilized several strategies to
      integrate MAPP and a variety of assessment tools into a continuous and seamless
      planning process that resulted in the Master Health Plan for Northern Kentucky
      2005. These strategies were developed from using many of the assessment and
      planning tools developed by the National Association of County and City Health
      Officials including MAPP, the Protocol for Assessing Community Excellence in
      Environmental Health, and the Assessment Protocol for Excellence in Public
      Health. Strategies included maintaining a consistent committee structure,
      integrating other processes into the MAPP process, combining community objectives
      and strategies into a Master Health Plan, and developing a unified evaluation
      plan.

PMID- 16103814
TI  - MAPP in action in San Antonio, Texas.
AB  - San Antonio was selected as an official Mobilizing for Action through Planning
      and Partnerships (MAPP) demonstration site by National Association of County and
      City Officials in 2000. The San Antonio Metropolitan Health District, under the
      leadership of Dr Fernando A. Guerra, agreed to facilitate the process. The MAPP
      process provided the San Antonio Metropolitan Health District, the local public
      health authority, a defined process for community health improvement, as well as
      a mechanism to help bridge the gap between public health and the community. The
      San Antonio Metropolitan Health District organized a Core Planning Team to lead
      the MAPP process in April 2001. By October 2002, the Core Planning Team was
      expanded to a full community working group named the Alliance for Community
      Health in San Antonio and Bexar County (Alliance). The Alliance identified six
      strategic issues, which eventually became the basis of the San Antonio Community
      Health Improvement Plan. The strategic issues are Public Policy, Data Tracking,
      Healthy Lifestyles, Promoting a Sense of Community, Access to Care, and Safe
      Environment. San Antonio's MAPP experience has been successful in bringing
      together the public health system partners, and establishing public health
      priorities collectively. The MAPP process has resulted in the development of many
      new initiatives, and, most important, has opened the door to many partnership
      opportunities in the future. The work of the Alliance, through the MAPP process,
      has helped to leverage resources for public health improvement in San Antonio,
      and has the potential to effect positive change in public health in the future.

PMID- 16103815
TI  - The role of dialogue in the NACCHO MAPP tool.

PMID- 16103816
TI  - Developing national performance standards for local public health systems.
AB  - Since the beginning of the 1990s, public health has struggled to measure its
      performance and capacity to carry out the core functions of public health
      practice, while facing increasing challenges within the ever-changing landscape
      of healthcare delivery, bioterrorism response, emerging infections, and other
      threats to the public's health. The article describes the development of a set of
      national performance standards for measuring how effectively public health
      systems deliver the 10 Essential Public Health Services. The standards were
      developed through a practice-driven approach that incorporated comprehensive
      field testing and iterative revisions. The standards represent a national
      consensus framework for measuring important aspects of public health practice.

PMID- 16103817
TI  - National Public Health Performance Standards assessment: first steps in
      strengthening North Dakota's public health system.
AB  - North Dakota, as a rural state with a decentralized public health system, has
      found the National Public Health Performance Standards Program useful in
      assessing performance of the state's public health system. The local instrument
      was used for local public health systems and on Native American reservations. A
      description of the process as well as aggregated results of the local performance
      assessment is presented. An importance ranking scale was combined with the
      performance scores to identify priority areas. Priority needs were specifically
      identified for developing community health profiles, working more closely with
      community partnerships, and increasing emphasis on health education activities.
      The process was a good opportunity for bringing partners together in local public
      health systems and for developing interest in using the more complete strategic
      planning tools in Mobilizing for Action through Planning and Partnerships.

PMID- 16103818
TI  - Utilizing a national performance standards local public health assessment
      instrument in a community assessment process: the Clarendon County Turning Point
      Initiative.
AB  - The Clarendon County Turning Point Initiative was launched with the goals of
      conducting a community-wide health assessment and developing a community health
      improvement plan. For the community assessment, the National Association of
      County and City Health Officials' (NACCHO's) Mobilizing for Action through
      Planning and Partnerships (MAPP) model was used. One of the assessments conducted
      through the MAPP model was the National Public Health Performance Standards Local
      Public Health Systems Assessment. The process for conducting the assessment using
      the local performance instrument is described. Clarendon County Turning Point
      Initiative conducted a one-and-a-half-day retreat to complete the local
      performance instrument. The committee planning the process identified and
      recruited stakeholders, collected data/information from stakeholders, and hired a
      consultant to facilitate the one-and-a-half-day retreat. The data analyzed with
      the local performance instrument identified opportunities and gaps in public
      health services in Clarendon County.

PMID- 16103819
TI  - National Public Health Performance Standards: are they a means of evaluating the
      local public health system?
AB  - The organizations, agencies, and entities within a community that contribute to
      the health of the public through the delivery of essential public health services
      define the body of the local public health system. These public, private, and
      voluntary entities have differing roles, relationships, and interactions within
      the system and for the population served. Combining the Genesee Valley Network
      and the Livingston County Community Health Partnership in the Year 2000 formed
      the Genesee Valley Health Partnership, Livingston County, New York, consisting of
      30 organizational members. In the spring of 2001, this partnership utilized the
      10 Essential Services outlined in Mobilizing for Action through Planning and
      Partnerships's Local Public Health System Assessment to measure the capacity and
      performance of Livingston County's local health system. Through a process that
      asked two basic questions, "What are the components, activities, competencies,
      and capabilities of our local public health system?" and "How are the Essential
      Services being provided to our community?" the Partnership determined the
      following: (1) in 8 out of the 10 Essential Services, the system met the standard
      by more than 50 percent; and (2) the system excelled in five of the Essential
      Services. The Partnership concluded that many valuable programs and services were
      conducted throughout the community; however, partners did not know what services
      were available, how to access those services, or how to coordinate with each
      other. The NPHPS provided a standard measurement for the local public health
      system and identified gaps in the system.

PMID- 16103820
TI  - Students in the community: MAPP as a framework for academic-public health
      practice linkages.
AB  - The importance of establishing and sustaining academic-public health practice
      linkages has been a point of emphasis in the Institute of Medicine reports on
      public health in 1988 and in 2003. One likely barrier to fostering such linkages
      is the absence of a clear framework that matches academic requirements to
      practice realities. This article describes how an academic-public health practice
      collaborative has used MAPP in a health planning course for Master of Public
      Health students over a 3-year period, allowing students the opportunity to work
      in communities with public health practitioners. The specific focus for each of
      these 3 years has varied, but underlying the work has been a consistent approach
      to teaching and working in communities with MAPP as the frame of reference. The
      outcome of this work has been of value to students and faculty, to public health
      department staff, and, most important, to the communities where this work has
      taken place. This suggests that there is great potential for using MAPP as a
      framework for establishing and strengthening academic-public health practice
      linkages.

PMID- 16103821
TI  - MAPP in the classroom: oxymoron or opportunity?
AB  - As Mobilizing for Action through Planning and Partnerships (MAPP) becomes
      increasingly important for community public health practice, it is critical to
      examine what learning MAPP entails as well as its barriers and benefits.
      Competency-based education and training interventions that prepare public health
      workers to effectively contribute to the implementation of MAPP in their
      communities face significant obstacles. Current public health education and
      training programs are poorly positioned to enhance MAPP-related competencies
      among significant numbers of public health students and workers. Establishing the
      community as the classroom for learning MAPP and forging links with professional
      education and lifelong professional development strategies are necessary for MAPP
      to be successful in promoting healthy communities.

PMID- 16103822
TI  - The MAPP training program evaluation.
AB  - This article reports on an evaluation of regional training programs designed to
      increase the knowledge and use of Mobilizing for Action through Planning and
      Partnerships (MAPP). The objectives for the MAPP training program included
      teaching participants about MAPP resources on the Web, providing participants
      with instruction about what MAPP is, and why it is important for community health
      improvement. Participants were also instructed on how to implement MAPP through a
      series of concrete steps such as mobilizing community partnerships, creating an
      action plan, conducting a series of assessments, and identifying strategic
      issues. An on-site survey with pretraining and posttraining questions and a
      follow-up survey were developed and administered to participants to assess their
      readiness levels to access MAPP resources and actively use and promote MAPP in
      their communities. The findings indicate that participants' knowledge of MAPP and
      confidence to use it improved as a result of training. Six months after training,
      participants' readiness levels increased from pretraining levels in the areas of
      incorporating MAPP into their roles, presenting MAPP to community partners, and
      using MAPP for community health improvement projects. Making changes in their
      organizations and communities to implement MAPP did not change significantly from
      pretraining levels. Just under half of training participants were implementing
      MAPP 6 months posttraining.

PMID- 16103823
TI  - Lessons from the MAPP demonstration sites.
AB  - This article describes one component of a three-part evaluation of a community
      health improvement model called MAPP (Mobilizing for Action through Planning and
      Partnerships). This component examined the use of MAPP by nine local public
      health agencies that acted as demonstration sites. Using qualitative data from
      telephone interviews, focus group data, and document reviews, the evaluators
      identified four themes associated with how MAPP was implemented and the factors
      that influenced implementation. A level of activity was assigned to each site for
      each of the four themes. Combining data from multiple demonstration sites,
      evaluators characterized common activities for each theme. Findings reveal that
      those sites with health director buy-in and full-time coordination for MAPP were
      associated with high levels of partnership development. The MAPP Web site, in its
      current state, does not appear to provide an advantage over using a printed copy
      of MAPP. Evaluation data from training programs and Web site users (the other two
      components of the evaluation) support key findings from the demonstration sites
      and reveal crosscutting themes for all components of the MAPP evaluation.
      Investigating other situational and contextual factors that influence the nature
      and success of MAPP implementation would be useful.

PMID- 16103824
TI  - Local partnerships for community assessment and planning.
AB  - PURPOSE: Community assessment is a core function of public health. National and
      state policies encourage local health departments (LHDs) to engage local partners
      in conducting community assessments. This study examined the prevalence,
      characteristics, and effectiveness of community assessment partnerships between
      LHDs and other organizations. METHODS: LHDs in Wisconsin completed a 2-stage,
      cross-sectional survey. A subset analysis of community assessment partnerships
      was conducted using descriptive, bivariate, and multivariate statistical methods.
      RESULTS: Ninety percent of LHDs reported a partnership focused on community
      assessment (n = 69). Sixty-six percent of community assessment partnerships had
      existed for three or more years, and all of these had implemented plans (n = 43).
      Community assessment partnerships were more likely than partnerships focused on
      other issues to have formed because of a mandate, to include many partners, and
      to receive some forms of financial support from the LHD. Partnerships focused on
      community assessment were no more likely to be effective than other types of
      partnerships. CONCLUSIONS: LHDs and community partners realize mutual benefits
      from collaborating on community assessment. Successful community assessment
      partnerships can be supported by building competencies in the public health
      workforce and sustaining partnerships for substantial periods of time.

PMID- 16103825
TI  - Public health education reform in context: a commentary on the Institute Of
      Medicine's Report "Who Will Keep The Public Healthy?".

PMID- 16103826
TI  - Practicing management and leadership: creating the information network for public
      health officials.
AB  - The Management Moment" is a regular column within the Journal of Public Health
      Management and Practice. Janet Porter, PhD, and Edward Baker, MD, MPH, MSc, are
      serving as The Management Moment Editors. Dr Porter is Associate Dean for
      Executive Education, The North Carolina Institute for Public Health, School of
      Public Health, at the University of North Carolina at Chapel Hill, and Dr Baker
      is Director of The North Carolina Institute for Public Health, School of Public
      Health, at the University of North Carolina at Chapel Hill. This column provides
      commentary and guidance on timely management issues commonly encountered in
      public health practice.

PMID- 16103827
TI  - Next steps for MAPP.

PMID- 16103828
TI  - Summary statement: treatment of the painful motion segment.

PMID- 16103829
TI  - Nucleus pulposus replacement: basic science and indications for clinical use.
AB  - STUDY DESIGN: A critical review of available and emerging nucleus pulposus
      replacement implants. OBJECTIVES: To review the biomechanics, design, and
      clinical data of currently available and developing nucleus pulposus replacement
      technologies. SUMMARY OF BACKGROUND DATA: The interest in minimally invasive
      treatment of degenerative disc disease has grown as the technology for
      intervertebral motion-sparing devices continues to improve. Replacement of
      nucleus pulposus without anular obliteration represents a tempting alternative to
      spinal fusion procedures. The aim in nucleus pulposus replacement is to slow
      adjacent level degeneration, restore normal loads to the diseased level, and
      restore segmental spinal biomechanics. METHODS: A literature review of currently
      available biomaterials, biomechanics, and available preclinical and clinical data
      on nucleus pulposus replacement implants. RESULTS: New synthetic biomaterials
      have recently been developed to closely mimic native biomechanics during
      compressive loading cycles of the intervertebral disc. This, in conjunction with
      improved understanding of global spine biomechanics, has allowed the development
      of novel nucleus replacement implants. These implants are currently at different
      stages of preclinical and clinical investigations. CONCLUSIONS: Although some of
      the newly designed prosthesis have shown some promising results in preclinical
      studies, rigorous short- and long-term clinical evaluations will be critical in
      evaluating their true efficacy.

PMID- 16103830
TI  - Indications for surgical fusion of the cervical and lumbar motion segment.
AB  - STUDY DESIGN: A literature review and the authors' clinical experience for the
      indication of fusion in the degenerative lumbar and cervical spine is provided.
      OBJECTIVE: To establish absolute and relative criteria for the indication for
      fusion in the degenerative cervical and lumbar spine. SUMMARY OF BACKGROUND DATA:
      Fusion in the cervical and lumbar degenerative spine is indicated under certain
      strict criteria. However, fusion in circumstances not meeting these criteria is
      controversial. METHOD: A review of the literature and the authors' experience
      concerning indication and criteria of fusion in degenerative, lumbar, and
      cervical spine is provided. RESULTS: Fusion for the unstable spine related to
      trauma, infection, and tumors is relatively accepted. However, indications for
      fusion for degenerative, cervical, and lumbar spine are more controversial.
      CONCLUSION: Lumbar and cervical fusion in the degenerative spine is frequently
      performed. Certain criteria have been established when a fusion should be
      considered. However, even these are not universally accepted. Strict prospective
      studies are needed to determine when a fusion of the degenerative, cervical, and
      lumbar spine is indicated. Patients with severe radicular pain may be considered
      for surgery after a comprehensive trial of conservative management. Fusion is
      usually necessary after a cervical discectomy, especially when spondylosis or
      osteophytic compression is present. Lumbar fusion is rarely indicated for routine
      discectomy. In patients with mechanical back or neck pain, surgery should only be
      considered after conservative measures have been exhausted and a radiographic
      abnormality is present at the symptomatic level, perhaps with pain concordant
      with discographic findings. Careful patient selection is the key to obtaining
      favorable surgical outcomes. In many cases, the goal may be a return to
      functionality rather than achieving a completely asymptomatic state.

PMID- 16103831
TI  - Treatment of the painful motion segment: cervical arthroplasty.
AB  - STUDY DESIGN: A retrospective review of the literature. OBJECTIVE: This work
      serves as a comprehensive update of cervical arthroplasty. SUMMARY OF BACKGROUND
      DATA: Cervical arthroplasty has developed as a means to preserve normal spinal
      motion after an anterior cervical discectomy. Preserving motion may lead to an
      acute improvement in patient outcome and may decrease the incidence of
      symptomatic adjacent segment disease in the long-term. METHODS: The literature
      concerning the outcomes following anterior cervical decompression and fusion, the
      indications for cervical arthroplasty, the indications and contraindications for
      arthroplasty, the surgical technique, and early outcome studies for those devices
      currently in U.S. FDA IDE trials are reviewed. RESULTS: The most data are
      available for the Prestige, Bryan, and ProDisc-C devices. While these devices all
      preserve normal segmental motion, the articulations vary (metal on metal, metal
      on polyurethane, and metal on ultra-high molecular weight polyethylene). Wear
      testing indicates that these devices will have a long life once implanted.
      Preliminary outcomes compare very favorably to anterior decompression and
      arthrodesis. CONCLUSIONS: Cervical arthroplasty is a promising new technology
      that may improve patient outcome following anterior cervical decompression.

PMID- 16103832
TI  - Current treatment strategies for the painful lumbar motion segment:
      posterolateral fusion versus interbody fusion.
AB  - STUDY DESIGN: Review of the literature. OBJECTIVES: We discuss the indications
      and contraindications for posterolateral lumbar fusion and posterior approaches
      to lumbar interbody fusion. We also review the advances in minimal access
      surgical techniques, graft materials, and osteobiologics. SUMMARY OF BACKGROUND
      DATA: Previously published data and our own surgical experience form the basis of
      this report. METHODS: A Pub Med online internet search for the keywords was
      performed. The pertinent articles were then cited. RESULTS: Posterior interbody
      fusion techniques have theoretical and demonstrable advantages over
      posterolateral fusion, but the former is also associated with greater morbidity.
      There are several approaches one may use to perform posterior interbody fusion,
      as well as multiple minimally invasive techniques and interbody spacer graft
      options. Bone morphogenetic protein offers an attractive alternative for
      achieving fusion. CONCLUSION: Fusion of painful motion segments is widely used to
      treat patients with degenerative low back pain. Successful arthrodesis may be
      achieved using either posterolateral fusion with pedicle screw fixation or
      posterior interbody fusion, depending on the patient's situation. These
      techniques may be accomplished with a variety of minimal access strategies and
      various graft and spacer technologies. The modern spine surgeon should be
      proficient in using all these options to treat the painful lumbar motion segment.

PMID- 16103833
TI  - Surgical treatment for the painful motion segment: matching technology with the
      indications: posterior lumbar fusion.
AB  - STUDY DESIGN: A convenience literature-based review of the different techniques
      of posterior lumbar fusion. OBJECTIVE: To describe the history, specific
      techniques, and outcomes of different methods of posterior lumbar fusion. The
      specific methods that were described include 1) uninstrumented posterior,
      posterolateral, and facet fusion, and 2) instrumented fusion using pedicle screws
      or facet screws. SUMMARY OF BACKGROUND DATA: There are various posterior fusion
      techniques available for the treatment of degenerative lumbar spine conditions.
      Each individual technique has specific technical demands, indications,
      advantages, and disadvantages which should be taken into consideration when
      performing these procedures. METHODS: The published scientific literature on the
      different methods of posterior lumbar fusion was reviewed. The history,
      indications, advantages, disadvantages, and clinical and radiographic outcomes
      were described based on the literature search. RESULTS/CONCLUSIONS: Posterior
      fusion techniques have been and will continue to be among the most commonly
      performed procedures in lumbar spine surgery. The different methods of fusion are
      well defined, as are the possible complications and outcomes. They are effective
      techniques when performed on appropriately selected patients by a surgeon
      knowledgeable in the techniques and indications. Further studies are needed
      regarding promising but relatively unproven developments such as minimally
      invasive surgery and the use of osteoinductive agents.

PMID- 16103834
TI  - Minimal access surgical techniques in the management of the painful lumbar motion
      segment.
AB  - STUDY DESIGN: Review article. OBJECTIVES: To provide an overview of current
      minimally invasive lumbar fusion techniques. SUMMARY OF BACKGROUND DATA:
      Minimally invasive lumbar fusion techniques have only recently been developed.
      The goals of these procedures are to reduce approach-related soft tissue injury
      while allowing the surgery to be conducted in an effective manner. METHODS.:
      Pertinent literature and the authors' clinical experience are reviewed. RESULTS:
      Minimally invasive techniques have been developed for intertransverse process,
      posterior lumbar interbody, and transforaminal lumbar interbody fusions. The
      indications, advantages, and disadvantages of each technique are described. It is
      emphasized that while they appear promising, the clinical results of these
      techniques remain preliminary with few long-term studies available for critical
      review. CONCLUSIONS: Preliminary clinical evidence suggests that minimally
      invasive lumbar fusion techniques will benefit patients with spinal disorders.

PMID- 16103835
TI  - Disc arthroplasty in the management of the painful lumbar motion segment.
AB  - STUDY DESIGN: A review of the published literature regarding lumbar arthroplasty.
      OBJECTIVE: To describe the current state of lumbar total disc replacement and, in
      particular, the recent clinical results of the Charite and ProDisc trials.
      SUMMARY OF BACKGROUND DATA: Lumbar fusion remains the surgical procedure of
      choice for patients with chronic low back pain unresponsive to nonsurgical
      management. Lumbar fusion is a strictly palliative procedure with suboptimal
      clinical results obtained by a significant proportion of patients. Adjacent
      segment disease is thought to limit the long-term clinical results with up to 20%
      of patients requiring secondary surgical interventions within the decade
      following a "successful" lumbar fusion. Total disc replacement has been developed
      as a potential means to improve the long-term outcome of these patients. METHODS:
      Literature review of total lumbar disc replacement. RESULTS: The surgical
      decision-making process, a description of current lumbar disc arthroplasty
      devices, and early clinical results are described. CONCLUSION: In appropriately
      chosen patients, lumbar disc arthroplasty provided clinical results similar to
      those obtained with interbody fusion at 2 years. The long-term results with
      respect to the effect of these devices on adjacent segment degeneration are not
      known, as the incidence of adjacent segment degeneration is not an endpoint of
      the current trials.

PMID- 16103836
TI  - Dynamic stabilization in the surgical management of painful lumbar spinal
      disorders.
AB  - STUDY DESIGN: A literature review. OBJECTIVE: To evaluate the mechanisms of
      action and effectiveness of posterior dynamic stabilization devices in the
      management of painful spinal disorders. SUMMARY OF BACKGROUND DATA: Dynamic
      stabilization may provide pain relief by altering the transmission of abnormal
      loads across the degenerated disc space. METHODS: A Medline search was conducted.
      RESULTS: Articles supporting abnormal load transmission across the disc space and
      clinical reviews of currently available posterior dynamic systems were included.
      CONCLUSIONS: Posterior dynamic stabilization systems may provide benefit
      comparable to fusion techniques, but without the elimination of movement. Further
      study is required to determine optimal design and clinical indications.

PMID- 16103837
TI  - Surgical treatment of the painful motion segment: matching technology with
      indications.
AB  - STUDY DESIGN: Literature review of current bone graft technology and bone graft
      substitutes used in spinal fusion applications. OBJECTIVE: We reviewed current
      bone graft technologies and identified the range of bioactive properties that
      each possesses, such as osteoconductivity, osteoinductivity, and structural, load
      bearing capabilities that can be used to either augment or replace autogenous
      bone graft in spinal fusions. SUMMARY OF BACKGROUND DATA: Bioactive materials are
      used in spinal fusion applications to encourage bone formation across an
      intervertebral motion segment. To be an effective replacement for autogenous bone
      grafts, a bioactive material must possess the properties of osteoinduction and
      osteoconduction. METHODS: Literature review. RESULTS: Platelet gel concentrates
      deliver nonspecific cytokines that influence local cells at the implantation
      site. Demineralized bone matrix acts as a bone graft enhancer that excludes
      fibrous tissue of muscle interposition in a fusion mass and is a mildly
      osteoinductive material. Bone morphogenetic proteins are an integral part of
      natural bone formation response. They function as differentiation factors that
      act on mesenchymal stem cells to induce bone formation. CONCLUSIONS: Patient
      derived therapies such as platelet gel concentrates contain cytokines that play a
      role in bone formation; however, none of them is capable of inducing the entire
      bone formation cascade. Clinical use of these concentrates could possibly
      interfere with new bone formation. The use of bone marrow aspiration and
      concentration techniques has not been convincingly studied in spinal fusions in
      lower order animal or human clinical studies. Demineralized bone matrix contains
      small and variable amounts of naturally occurring bone morphogenetic proteins.
      These products can only function as bone graft extenders. Recombinant bone
      morphogenetic protein products contain much more highly concentrated and focused
      amounts of bone morphogenetic proteins, and some have been shown to be clinically
      effective bone graft replacements.

PMID- 16103838
TI  - Dynamic interspinous process technology.
AB  - STUDY DESIGN: A literature review. OBJECTIVES: To evaluate the mechanisms of
      action and effectiveness of interspinous distraction devices in managing
      symptomatic lumbar spinal pathology. SUMMARY OF BACKGROUND DATA: Fusion
      operations have traditionally been used to manage many disorders of the lumbar
      spine related to deformity, pain, or instability. Concern over the long-term
      effects of fusion on adjacent segments has led to the development of the concept
      of dynamic stabilization. METHODS: A Medline search was performed using the key
      words "interspinous implants," "interspinous devices," and "lumbar dynamic
      stabilization." The abstracts of each were reviewed. Relevant articles were
      reviewed in detail and other appropriate references obtained. In addition, when
      available, nonpublished manufacturer's information was reviewed. RESULTS:
      Articles describing the following implants were included in this review: the
      Minns Device, the Interspinous "U," the Diam, the Wallis Implant, and the X STOP.
      CONCLUSIONS: These devices continue to be evaluated in clinical trials. Early
      results suggest a possible role in the management of degenerative disorders of
      the lumbar spine.

PMID- 16103839
TI  - Interrater reliability of scoring of pain drawings in a self-report health
      survey.
AB  - STUDY DESIGN: Study of interrater reliability. OBJECTIVE: To assess the
      interrater reliability of data from pain drawings scored by multiple raters and
      the consistency of the subsequent classification of cases of widespread pain.
      SUMMARY OF BACKGROUND DATA: In large health surveys, pain drawings used to
      capture self-reported pain, and to classify cases of widespread pain, are often
      scored by several raters. The reliability of multiple rater scoring of pain
      drawings has not been investigated. METHODS: As part of a postal survey sent to
      adults 50 years and older, subjects were asked to shade their pain on a blank
      body manikin. The first 50 pain drawings in which respondents had shaded pain
      were selected for this study. Eight nonclinical staff were trained to score pain
      drawings using transparent templates divided into 50 body areas. Interrater
      reliability was assessed by comparing the scoring of "pain" or "no pain" for all
      50 areas of each pain drawing. RESULTS: Complete scoring agreement among all
      raters was observed for at least 78% of pain drawings across all body areas
      (kappa > 0.60). The raters had complete agreement in 42 of 50 areas in 90% or
      more of pain drawings. From the raters' scoring of pain areas, there was complete
      agreement on the presence or absence of widespread pain for 49 of 50 pain
      drawings (98% agreement, Kappa = 0.98). CONCLUSIONS: This study shows that
      multiple raters, with training and guidelines, can reliably score pain drawings,
      and high consistency in the subsequent classification of cases of widespread pain
      can be obtained from such data.

PMID- 16103840
TI  - Predictors of outcome in neck and shoulder symptoms: a cohort study in general
      practice.
AB  - STUDY DESIGN: An observational prospective cohort study in general practice.
      OBJECTIVES: To describe the clinical course and to identify predictors of
      recovery, changes in pain intensity, and changes in functional disability in
      patients with neck or shoulder symptoms at 3- and 12-month follow-up. SUMMARY OF
      BACKGROUND DATA: Knowledge on the clinical course and predictors of outcome in
      neck and shoulder symptoms is limited. Such knowledge would facilitate treatment
      decisions and may help to inform patients about their prognosis. METHODS: Four
      hundred and forty-three patients who consulted their general practitioner with
      neck or shoulder symptoms participated in the study. Baseline scores of pain and
      disability, symptom characteristics, sociodemographic and psychological factors,
      social support, physical activity, general health, and comorbidity were
      investigated as possible predictors of recovery, changes in pain intensity, and
      changes in functional disability using multiple regression analyses. RESULTS: The
      recovery rate was low; 24% of the patients reported recovery at 3 months and 32%
      reported recovery at 12-month follow-up. Duration of the symptoms before
      consulting the GP and a history of neck or shoulder symptoms increased the
      probability of an unfavorable outcome. Furthermore, less vitality and more
      worrying were consistently associated with poorer outcome after 3 and 12 months.
      The area under the receiver-operator characteristic curve for the model
      predicting recovery was 0.8 at 3 months and 0.75 at 12 months. The explained
      variance of the models on pain and functional disability ranged from 43 to 54%.
      CONCLUSIONS: The results found in this study indicate that besides clinical
      characteristics, psychological factors also predict the outcome of neck and
      shoulder symptoms.

PMID- 16103841
TI  - Scoliosis in association with infantile hypophosphatasia: a case study in two
      siblings.
AB  - STUDY DESIGN: A case study of scoliosis in two siblings with infantile
      hypophosphatasia and review of literature are presented. OBJECTIVES: To report
      the rare occurrence of scoliosis in two siblings with infantile hypophosphatasia
      and detail problems in the surgical management of scoliosis in this rare disease.
      SUMMARY OF BACKGROUND DATA: To the authors' knowledge there is only one reported
      case of scoliosis in infantile hypophosphatasia. However, there is no report
      describing the nature of the curve, its progression, or the surgical management
      of scoliosis in infantile hypophosphatasia. METHODS: The first sibling was
      diagnosed shortly after birth to have scoliosis that progressed rapidly despite
      brace treatment. At 4 years, he underwent anterior convex arthrodesis and
      posterior T6-L1 Luque trolley stabilization. Because of further curve
      progression, he had to undergo corrective anterior and posterior osteotomies,
      stabilization, and fusion at 11 years of age. The second sibling was diagnosed to
      have scoliosis at the age of 3 years and underwent anterior thoracoscopic release
      and posterior Luque trolley stabilization. RESULTS: The first sibling with a mild
      form of infantile hypophosphatasia had to undergo multiple procedures to attain
      fusion and arrest of curve progression. The second sibling with a severe variety
      of infantile hypophosphatasia surprisingly attained a spontaneous fusion of the
      curve following the initial correction and stabilization with no further
      progression at 9-year follow-up. CONCLUSIONS: Curve progression and fusion rates
      following scoliosis correction are not related to the disease severity or
      biochemical findings. These rapidly progressive curves are amenable to surgical
      correction despite the unfavorable metabolic nature of the disease. Hypercalcemia
      and seizures responding to pyridoxine are complications in the postoperative
      period of which the surgeon should be aware.

PMID- 16103842
TI  - Unique combination of lumbosacral junction injury with open pelvic ring
      disruption and acetabulum fracture: case report.
AB  - STUDY DESIGN: A case report of a complex spondylo-pelvic injury combining a
      traumatic spondylolysis and burst fracture of the fifth lumbar vertebra, with an
      open pelvic ring disruption and a fracture of the acetabulum. OBJECTIVES: To
      describe the mechanism, diagnostic approach, and rationale for treatment of this
      very rare and complex injury pattern, and finally to present the results of the
      treatment. SUMMARY OF BACKGROUND DATA: Traumatic spondylolysis of the fifth
      lumbar vertebra is a very uncommon type of injury, with few cases being reported
      in the literature. Combination of such an injury with pelvic ring and acetabular
      fractures has never been reported in the past. METHODS: The patient was referred
      to our institution for definitive treatment after initial treatment at a local
      hospital involving laparotomy, defunctioning colostomy, and symphyseal plating.
      Accurate delineation of the complex injury pattern was established on
      computerized tomography with 3-dimensional multiplanar reconstruction, and
      magnetic resonance imaging of both the spine and pelvis. Definitive stabilization
      of the injury was made by posterior lumbopelvic segmental fixation with
      posterolateral fusion and open reduction and internal fixation of the acetabular
      fracture. RESULTS: At 2 years after surgery, the patient was ambulatory, with an
      ankle-foot orthosis, and almost completely pain free. He was able to perform
      manual work. CONCLUSIONS: Complex associated injuries of the spondylo-pelvic
      junction and pelvis are always a challenge to treat because they demand careful
      assessment, stabilization of the patient, meticulous imaging, and a
      multidisciplinary approach.

PMID- 16103843
TI  - Cervical stenosis presenting with acute Brown-Sequard syndrome: case report.
AB  - STUDY DESIGN: An unusual case report of cervical stenosis presenting with the
      Brown-Sequard syndrome. Technical considerations and a literature review are
      discussed. OBJECTIVE: To evaluate cervical stenosis as an etiology of the Brown
      Sequard syndrome and whether surgical decompression is effective for improving
      neurologic outcome. SUMMARY OF BACKGROUND DATA: Of the causes of the Brown
      Sequard syndrome, intrinsic cervical spine pathology has rarely been reported in
      the literature. We report the first case of a chronic cervical stenosis
      presenting with an acute Brown-Sequard syndrome after a severe coughing episode.
      METHODS: A 75-year-old woman with a previous history of cervical stenosis had
      sudden onset of weakness develop in the right upper and lower extremities, and
      disruption of pain and temperature sensation on the left side of her body after
      an episode of severe coughing associated with pneumonia. Magnetic resonance
      imaging of the cervical spine revealed severe canal stenosis from C3 through C7,
      with diffuse intramedullary hyperintensity consistent with myelomalacia of the
      cervical cord. A decompressive cervical laminectomy with fusion was performed.
      RESULTS: The patient improved neurologically, with near complete resolution of
      the right hemiparesis at 6-month follow-up. CONCLUSION: Multilevel chronic
      cervical stenosis can present with an acute Brown-Sequard syndrome. Cervical
      laminectomy and decompression are effective treatments for cervical stenosis with
      an acute Brown-Sequard syndrome.

PMID- 16103844
TI  - Sacral insufficiency fractures following multilevel instrumented spinal fusion:
      case report.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To report a series of patients in whom
      sacral insufficiency fractures developed following multilevel spinal fusion with
      instrumentation. SUMMARY OF BACKGROUND DATA: Rigid spinal fusion with
      instrumentation results in abnormal distribution of forces in the spine. These
      forces have the potential to cause failure of adjacent segments, especially in
      older, osteopenic individuals. Sacral insufficiency fractures following lumbar
      sacral fusion may be the result of these abnormal forces. However, this
      complication is not well described in the literature. METHODS: Three patients who
      sustained sacral fractures after instrumented lumbar-sacral fusion performed for
      degenerative disease of the spine are discussed. History, physical examination
      findings, and radiographic features are presented, along with a brief review of
      the pertinent literature. RESULTS: All 3 patients in our series started
      complaining of new-onset buttock pain a few weeks after their operative
      procedure. Radiographic examination revealed that they had transverse sacral
      fractures just below the fusion instrumentation. Nonoperative, conservative
      treatment was performed. At final follow-up, the fractures had healed completely
      and the patients' complaints had resolved. CONCLUSION: Patients who complain of
      new-onset buttock pain following multilevel lumbar-sacral fusion with
      instrumentation should be evaluated for sacral insufficiency fractures,
      especially if they have been sitting for prolonged periods. Conservative
      treatment seems to be sufficient.

PMID- 16103845
TI  - Symptomatic hematoma of cervical ligamentum flavum: case report.
AB  - STUDY DESIGN: A case of symptomatic hematoma of cervical ligamentum flavum.
      OBJECTIVE: To report the first ligamentum flavum hematoma in the cervical spine
      and review the reported cases. SUMMARY OF BACKGROUND DATA: A herniated nucleus
      pulposis, spondylosis, epidural hematoma or abscess, neoplasm, or some pathology
      of the ligamentum flavum, such as hypertrophy, ossification, or calcification,
      are the most common causes of spinal cord and nerve root compression. A
      ligamentum flavum hematoma has also been reported as a cause of compression of
      the cauda equina and lumbar nerve roots but has never been found in the cervical
      spine. METHODS: A 72-year-old man presented with left upper arm pain and left
      hemiparesis following traditional massage therapy. Admission magnetic resonance
      images showed a posterior oval-shaped mass that was continuous with the
      ligamentum flavum at C3-C4 level. RESULTS: A C3-C4 laminectomy for decompression
      and resection of the lesion was performed. One year after surgery, the patient
      remained neurologically intact and symptom-free. CONCLUSIONS: Hematoma of the
      ligamentum flavum occurring in the cervical spine has never been reported
      previously. Repeated trivial injury on a degenerative ligamentum flavum might be
      the leading predisposing factor. Spine surgeons should be aware of a hematoma in
      the ligamentum flavum as a possible cause of spinal cord or root compression,
      especially in the mobile cervical and lumbar spine.

PMID- 16103847
TI  - A randomized controlled trial of an educational intervention to prevent the
      chronic pain of whiplash associated disorders following rear-end motor vehicle
      collisions.
AB  - STUDY DESIGN: Concealed allocation, multicenter, single-blind, randomized
      controlled clinical trial. OBJECTIVE: To assess the efficacy of an educational
      video in the tertiary prevention of persistent WAD symptoms following rear-end
      motor vehicle collisions (MVCs). SUMMARY OF BACKGROUND DATA: Whiplash-associated
      disorders (WAD) are an important and costly health problem. There is a lack of
      high quality evidence surrounding efficacy of treatments for WAD. Existing
      research supports active interventions and early return to regular activities.
      METHODS: Consecutive patients presenting to four tertiary care emergency
      departments following rear-end MVCs were eligible. Following informed consent,
      patients were allocated, using central randomization, to receive an educational
      video plus usual care or usual care alone. The video provided reassurance, and
      advice about posture, return to regular activities, exercises, and pain-relief
      methods. Data were collected by telephone using standardized questionnaires. The
      primary outcome was presence of Persistent WAD Symptoms at 24 weeks postinjury,
      based on the frequency and severity of neck, shoulder, or upper back pain. The
      absolute difference in proportion of patients with persistent WAD symptoms and
      rate ratios were calculated. Changes in pain scores were compared using the Mann
      Whitney U test. RESULTS: The intervention (n = 206) and control (n = 199) groups
      were similar at baseline (mean age 38.4 years; 64% female). Overall, the
      proportion of subjects with Persistent WAD Symptoms decreased from 89.1% at
      baseline to 33.6% at 24 weeks after injury. At 24 weeks, the proportion of
      subjects with persistent WAD symptoms in the intervention group was 7.9% (95% CI,
      -2.0, 17.8) lower than the control group. The median improvement in pain score at
      24 weeks was 3 for the intervention group and 2 for the control group (P =
      0.016). CONCLUSION: The presence of persistent WAD symptoms following simple rear
      end MVCs was high in this sample. The video group demonstrated a trend toward
      less severe WAD symptoms. We recommend evaluating other educational interventions
      that could reduce WAD symptoms.

PMID- 16103848
TI  - Human evolution and the development of spondylolysis.
AB  - STUDY DESIGN: We propose that chronic spondylolytic defects at L5 are influenced
      by insufficient differential mediolateral distances between inferior articular
      facets of L4 and the superior facets of S1, which results in these structures
      impinging on adjacent sides of the par interarticularis during hyperlordosis.
      Individuals with adequate increase in interfacet distances from L4 through S1 are
      less likely to develop or maintain defects. OBJECTIVES: We test the above
      hypothesis by comparing the transverse interfacet dimensions throughout the
      lumbar columns of normal and spondylolytic individuals. SUMMARY OF BACKGROUND
      DATA: Spondylolysis is a common condition, yet its etiology is poorly understood.
      It is generally considered to be the result of a vaguely defined fatigue fracture
      through the pars interarticularis. The cause(s) of spondylolysis, however, have
      not been clearly identified. METHODS: Lumbar vertebrae from the Hamann-Todd
      osteological collection at the Cleveland Museum of Natural History were examined.
      Thirty individuals with bilateral spondylolysis at L5 were compared with 30 age-
      and sex-matched controls. Differences in transverse distances between articular
      facets and in transverse breadths of vertebral bodies were compared using two
      tailed t tests. RESULTS: Results show that normal individuals have a
      significantly greater increase in interfacet dimensions progressing down the
      spine from L4 to S1 than do those with spondylolysis. These differences are not
      the result of normal individuals having increasingly large vertebrae, as results
      are significant even when standardized for vertebral body breadth. Vertebral body
      size itself does not differ systematically between groups. CONCLUSIONS:
      Spondylolysis is the direct result of contact pressures on both sides of the pars
      interarticularis resulting from inadequate separation between the inferior
      articular processes of L4 and the superior articular facets of S1. Individuals
      lacking sufficient increase in transverse interfacet dimensions in their lumbar
      columns are at greater risk of developing and maintaining spondylolytic defects.

PMID- 16103849
TI  - The elastic fiber network of the anulus fibrosus of the normal and scoliotic
      human intervertebral disc.
AB  - STUDY DESIGN: Immunohistochemical study of elastic fibers in human intervertebral
      discs (IVD) collected at surgery from patients with scoliosis. OBJECTIVES: To
      compare the elastic fiber network in scoliotic discs (idiopathic scoliosis or
      neuromuscular scoliosis) to that of control (normal) discs. To study whether the
      change in elastic fiber organization could contribute to the progression of
      spinal deformity. SUMMARY OF BACKGROUND DATA: Elastin and elastic fibers have
      been identified previously in human IVD but were believed to contribute little to
      the tissue's mechanical properties. However, a recent immunohistochemical study
      has revealed an abundant and organized elastic fiber network in bovine IVD,
      indicating that elastic fibers could play an important mechanical role. This
      article reports the organization of elastic fibers in human IVD and the changes
      of elastic fiber organization in scoliosis. METHODS: Intact wedges of IVD were
      obtained from patients undergoing surgery for scoliosis (aged 12-22 years).
      Control discs were obtained from a patient (aged 12 years) with a spinal tumor
      and a trauma patient (aged 17 years). The discs were dissected to give radial
      slices and were snap frozen. Frozen sections were cut and digested with
      hyaluronidase to remove glycosaminoglycans. Micrographs of the sections were
      examined by polarized light to visualize collagen organization. The elastic fiber
      network was visualized immunohistochemically or by histochemical staining with
      orcein. RESULTS: A highly organized elastic fiber network, similar to that
      described in bovine discs, was revealed in the control human discs. In the anulus
      fibrosus of control discs, dense elastic fibers were located between adjacent
      lamellae, with fibers also present within individual lamellae. Elastic fibers
      appeared to be long (>200 microm) and straight in outer anulus, whereas in inner
      anulus, they nearly ran parallel to each other and at an angle of approximately
      60 degrees or 120 degrees to those in adjacent lamellae. However, in scoliotic
      discs, elastic fibers were sparse, and the collagen and elastic fiber networks
      were disorganized with loss of lamellar structure. Cell clusters, one of typical
      degenerative feature, were seen in scoliotic discs but not in age-matched control
      discs. CONCLUSIONS: Our results reveal an abundant and organized network of
      elastic fibers in the adolescent (12 and 17-year-olds) human IVD, and suggest
      that elastic fiber network plays a significant biomechanical role. This network
      is sparse and disrupted in scoliotic discs, and could be involved in the
      progression of the spinal deformity.

PMID- 16103850
TI  - The magnitude of mechanical allodynia in a rodent model of lumbar radiculopathy
      is dependent on strain and sex.
AB  - STUDY DESIGN: This study examined the differences in tactile hypersensitivity
      across 6 different strains of male mice, and between male and female rats of 3
      different strains in a rodent model of low back pain associated with lumbar
      radiculopathy. OBJECTIVE: We investigated the possibility that differences in
      tactile allodynia following the same nerve root injury are affected by genotype
      and sex in rodents. SUMMARY OF BACKGROUND DATA: Low back pain associated with
      radiculopathy affects countless people throughout the world, encompassing a wide
      range of individual pain susceptibility. The roles of genetics and sex on
      differences in nociceptive sensitivities following lumbar nerve root injury have
      yet to be fully characterized. METHODS: Six strains of mice (BALB/cJ, CBA/J,
      C57BL/6J, 129P3/J, C3H/HeJ, and C58/J; all males) and male and female Sprague
      Dawley, Holtzman, and Long-Evans rats underwent a lumbar nerve root injury
      followed by assessment of tactile allodynia. RESULTS: The most sensitive mouse
      strains following nerve root injury were: 129P3/J, C58/J, and BALB/cJ; and the
      less sensitive strains were: C57BL/6J, C3H/HeJ, and CBA/J. Female Sprague Dawley
      and Long-Evans rats displayed increased hypersensitivity following nerve root
      injury compared to males. No sex differences were observed in Holtzman rats.
      CONCLUSIONS: Different mouse strains, and male and female rats that are exposed
      to identical nerve root injuries have diverse levels of tactile hypersensitivity,
      supporting the hypothesis that genetic factors and sex play a key role in
      radicular pain. Our results correlate with data compiled in identical mouse and
      rat strains after L5-L6 nerve ligation, suggesting that the precise nature of the
      injury is not relevant to the inheritance of neuropathic symptom sensitivity.

PMID- 16103851
TI  - Characterization of pain and pharmacologic responses in an animal model of lumbar
      adhesive arachnoiditis.
AB  - STUDY DESIGN: The study used a small animal laminectomy model with kaolin to
      investigate the relationship of cauda equina pathology to pain, and the effects
      of systemic and intrathecal drugs to reduce pain. OBJECTIVE: To determine if
      higher amounts of cauda equina adhesions produce increased pain-related behavior
      following laminectomy and epidural kaolin application. SUMMARY OF BACKGROUND
      DATA: Clinically, the relationship of cauda equina pathology to pain is
      controversial. An established animal model produces cauda equina adhesions. The
      correlation of this anatomic pathology with pain-related behavior has not been
      examined. METHODS: A laminectomy was performed in Sprague-Dawley rats at the L5
      L6 vertebrae, and kaolin was applied extradurally. Sham control animals had
      vertebrae exposed but no laminectomy/kaolin. Animals were monitored for pain
      related behavior using vocalization in response to straight leg raising.
      Histology was performed at 6 weeks postoperatively. Laminectomy animals were
      tested with systemic or intrathecal drugs to reduce straight leg raising
      vocalizations. RESULTS: In laminectomy animals, the pain response developed over
      6 weeks, with vocalizations increasing from 0 to 1.65, out of 5 leg lifts. Cauda
      equina clumping was related to pain severity. Systemic morphine 3 mg/kg, but not
      1 mg/kg, decreased vocalization to straight leg raising. Intrathecal morphine at
      30 nmol, but not 10 nmol, gabapentin at 60 nmol, but not 20 nmol, decreased
      vocalizations. Intrathecal clonidine up to 90 nmol did not reduce vocalization.
      CONCLUSIONS: An animal model of adhesive lumbar arachnoiditis yields a
      quantifiable pain-related response that can be used to evaluate the effects of
      various analgesic interventions.

PMID- 16103852
TI  - Bone displacement and the role of longitudinal ligaments during balloon
      vertebroplasty in traumatic thoracolumbar fractures.
AB  - STUDY DESIGN: In a human cadaveric burst fracture model with and without
      longitudinal ligament damage, the amount of anterior and posterior bone
      displacement (ABD, PBD) during balloon vertebroplasty after pedicle-screw
      instrumentation was investigated quantitatively. OBJECTIVES: To investigate, in a
      burst fracture model with and without longitudinal ligament damage, the amount of
      ABD, PBD, and cement leakage at various phases during balloon vertebroplasty in
      combination with pedicle-screw instrumentation. SUMMARY OF BACKGROUND DATA: The
      role of intact longitudinal ligaments in traumatic spine fractures, for
      prevention of bone retropulsion and subsequent reduction, has been discussed in
      several studies but is still up for debate. In a recent human cadaveric burst
      fracture study, inflatable bone tamps and calcium phosphate cement were used for
      the augmentation of the anterior column after pedicle-screw instrumentation. The
      additional balloon vertebroplasty procedure was found to be feasible and safe,
      but no data pertaining to unwarranted bone displacement or cement leakage during
      the procedure are available for burst fractures with damaged longitudinal
      ligaments. METHODS: Ten thoracic and 10 lumbar burst fractures, with rotation or
      flexion components, were created, and balloon vertebroplasty with calcium
      phosphate cement was performed after pedicle-screw instrumentation. Volumetric
      datasets (using the 3-dimensional (3D) rotational x-ray imaging technique) of the
      fractures were obtained during the following phases: intact, fractured, after
      reduction and stabilization with pedicle-screws, after inflation of the balloons,
      after deflation and removal of the balloons, and after injection of the cement.
      The amount of ABD and PBD was measured on reconstructed sagittal images and
      recorded together with the presence of extracorporal cement leakage. The
      continuity of the longitudinal ligaments was assessed after anatomic dissection.
      RESULTS: During the balloon vertebroplasty procedure, a significant (P < 0.05)
      increase of ABD (at both thoracic and lumbar level) and PBD (thoracic level)
      occurred after inflation of the balloons. After deflation and subsequent
      injection of the cement, however, the ABD and PBD returned to the preinflation
      levels. The absolute amount of ABD and PBD (<1 mm) during inflation was
      considered of little clinical importance. No differences in ABD or PBD were
      observed for specimens with or without continuity of the corresponding
      longitudinal ligament, irrespective of the level, at any of the phases during the
      experiment (P > 0.5 in all cases). A small amount of cement leakage was observed
      in the psoas compartment of one specimen with intact longitudinal ligaments.
      CONCLUSIONS: It is suggested that balloon vertebroplasty after pedicle-screw
      instrumentation may safely be used, in terms of bone displacement and cement
      leakage, in fracture types where damage to longitudinal ligaments is to be
      expected.

PMID- 16103853
TI  - The reduction of endplate fractures during balloon vertebroplasty: a detailed
      radiological analysis of the treatment of burst fractures using pedicle screws,
      balloon vertebroplasty, and calcium phosphate cement.
AB  - STUDY DESIGN: In a human cadaveric burst fracture model, the amount of endplate
      fracture reduction after posterior instrumentation and balloon vertebroplasty was
      investigated quantitatively. OBJECTIVES: To assess, in a burst fracture model,
      the vertebral body and adjacent disc heights, in parallel sagittal planes with 3
      dimensional (3D) rotational x-ray imaging, at various phases during pedicle screw
      fixation and subsequent balloon vertebroplasty. SUMMARY OF BACKGROUND DATA: In
      recent human cadaveric thoracolumbar fracture studies, it was found that
      vertebral body height could be restored significantly with inflatable bone tamps.
      However, limited quantitative data exist on the amount of fracture reduction that
      can be achieved and how much of the reduction will be lost after deflation and
      removal of the bone tamps before the cement is injected. METHODS: Twenty burst
      fractures were created and balloon vertebroplasty with calcium phosphate cement
      was performed after pedicle screw instrumentation. A 3D dataset was obtained
      during the following phases: intact, fractured, after reduction and stabilization
      with pedicle screws, after inflation of the balloons, after deflation and removal
      of the balloons, after injection of the cement. The fractured vertebral body and
      adjacent disc heights were measured from five reconstructed sagittal images and
      compared for the six phases of the procedure. Furthermore, the difference between
      the vertebral body height centrally and peripherally was calculated. RESULTS: The
      mean vertebral body height at the thoracic level was Tintact = 19.5 +/- 2.2 mm,
      Tfractured = 14.6 +/- 3.8 mm, Treduction = 17.3 +/- 2.2 mm, Tinflation = 20.1 +/-
      2.0 mm, Tdeflation = 18.0 +/- 2.0 mm, and Tcement = 17.8 +/- 1.8 mm. The overall
      change in vertebral body height between these phases was significant (P < 0.001).
      At the lumbar level the mean vertebral body height was Tintact = 23.2 +/- 3.8 mm,
      Tfractured = 14.7 +/- 3.0 mm, Treduction = 18.4 +/- 2.5 mm, Tinflation = 23.2 +/-
      3.5 mm, Tdeflation = 19.3 +/- 2.3 mm, and Tcement = 20.2 +/- 2.8 mm. The overall
      change in MCVBH between these phases was also significant (P < 0.001). The
      increase in vertebral body height resulted in a decrease of the adjacent disc
      height. No difference was found for the amount of endplate reduction in the
      center or at the periphery. No leakage of cement was detected in the spinal
      canal. CONCLUSIONS: Reduction of endplate fractures, both in the center and at
      the periphery, seems feasible and safe with combined fracture reduction and
      balloon vertebroplasty. The endplate fracture reduction that was gained by
      inflation of the bone tamps could not be maintained after deflation.

PMID- 16103854
TI  - In vitro, biomechanical comparison of an anterior lumbar interbody fusion with an
      anteriorly placed, low-profile lumbar plate and posteriorly placed pedicle screws
      or translaminar screws.
AB  - STUDY DESIGN: An in vitro biomechanical comparison of anteriorly placed lumbar
      plates, pedicle screws, and translaminar screws in the anterior lumbar interbody
      fusion (ALIF) setting. OBJECTIVES: To determine whether an anteriorly placed
      lumbar plate reduces the flexibility in terms of neutral zone and range of motion
      of a simulated ALIF, and to compare this reduction in flexibility to that
      provided by posteriorly placed pedicle screws and translaminar screws. SUMMARY OF
      BACKGROUND DATA: Pedicular and translaminar facet fixation add stability and
      increase fusion rates, compared with ALIF alone. An anteriorly placed lumbar
      plate has been introduced to provide stability without the need for a secondary
      approach. However, this plate has not been evaluated biomechanically. METHODS:
      Seven intact, cadaveric lumbar motion segments were tested to +/- 7.5 Nm in
      flexion-extension, lateral bending, and axial torsion. Specimens were retested
      after ALIF, and after subsequent instrumentation with pedicle screws,
      translaminar screws, and anterior lumbar plates. The range of motion and neutral
      zone were measured from resulting flexibility curves. RESULTS: Mean (+/- standard
      deviation) flexion-extension range of motion for intact segments (9.9 degrees +/-
      3.1 degrees ) was significantly reduced to 7.7 degrees +/- 1.8 degrees after ALIF
      (P = 0.02), and was further reduced to 3.0 degrees +/- 0.9 degrees with lumbar
      plates (P < 0.001), 1.5 degrees +/- 0.6 degrees with pedicle screws (P < 0.001),
      and 0.9 degrees +/- 0.4 degrees with translaminar screws (P < 0.001). All 3
      devices also reduced flexion-extension neutral zone and torsion neutral zone and
      range of motion, compared with ALIF alone (P < 0.05). Lumbar plates did not
      decrease lateral bending range of motion or neutral zone (P > 0.05), whereas
      pedicle and translaminar screws did (P < 0.05). CONCLUSIONS: Although not as
      rigid as pedicle or translaminar screws, anterior lumbar plating does add
      significant stability to an ALIF and may provide a valuable, single-approach
      alternative to supplemental posterior fixation.

PMID- 16103855
TI  - Frontal impact causes ligamentous cervical spine injury.
AB  - STUDY DESIGN: Whole cervical spine model with muscle force replication was
      subjected to simulated frontal impacts of increasing severity, and resulting
      injuries were evaluated via flexibility testing. OBJECTIVES: To identify and
      quantify cervical spine soft tissue injury and the injury threshold acceleration
      due to frontal impact. SUMMARY OF BACKGROUND DATA: Cervical spine instability may
      result from automotive collisions. No previous studies have quantified soft
      tissue injuries due to frontal impact. METHODS: Six human cervical specimens
      (occiput-T1) with muscle force replication were subjected to frontal impacts of
      4, 6, 8, and 10 g. Before frontal impact, baseline flexibility data were
      collected following a 2 g simulation. Flexibility parameters of total (flexion
      plus extension) neutral zone (NZ), flexion NZ, total range of motion (ROM), and
      flexion ROM were obtained following each impact and compared with baseline
      flexibility. Injury was a significant increase (P < 0.05) in intervertebral
      flexibility due to frontal impact over baseline. Injury threshold was the lowest
      T1 peak acceleration that caused injury. RESULTS: The injury threshold
      acceleration was 8 g, as determined by significant increases of 12.6 to 51.4%
      over the baseline flexibility, in the C4-C5 total NZ, and the C6-C7 total NZ,
      flexion NZ, total ROM, and flexion ROM. Following 10 g, significant increases in
      flexibility parameters were observed at C2-C3, C3-C4, C4-C5, C6-C7, and C7-T1.
      CONCLUSIONS: Middle (C2-C3 to C4-C5) and lower (C6-C7 and C7-T1) cervical spine
      were at risk for injury during frontal impacts, for the experimental conditions
      studied.

PMID- 16103856
TI  - Radiographic outcomes of anterior spinal fusion versus posterior spinal fusion
      with thoracic pedicle screws for treatment of Lenke Type I adolescent idiopathic
      scoliosis curves.
AB  - STUDY DESIGN: Analysis of radiographic outcomes following surgical correction of
      scoliosis. OBJECTIVES: To compare the curve correction and derotation following
      anterior spinal fusion (ASF) versus posterior spinal fusion (PSF) with thoracic
      pedicle screws. SUMMARY OF BACKGROUND DATA: The benefits of ASF in adolescent
      idiopathic scoliosis include saving distal fusion levels and historically greater
      correction and derotation compared with PSF. However, comparative studies between
      ASF and PSF have generally consisted only of posterior hook instrumentation or
      hybrid constructs, with no direct comparisons between anterior fusion and
      thoracic pedicle screw (TPS) series. METHODS: We performed a retrospective review
      of the radiographic and medical records of 40 patients (two curve-matched groups)
      with Lenke Type I main thoracic adolescent idiopathic scoliosis. There were 20
      patients who underwent open ASF with single-rod instrumentation with a mean age
      at surgery of 15 years + 6 months (range, 12-20 years) and 20 patients who
      underwent PSF with TPS constructs with a mean age at surgery of 13 + 6 (range, 12
      15). Radiographic follow-up averaged 44.1 month (24-80) for the ASF group and
      55.1 month (25-83) for the PSF/TPS group. We evaluated the sagittal alignment,
      Cobb angles, rib hump deformity (RH), apical rib spread difference (ARSD), and
      apical vertebral body-rib ratio (AVB-R), measures of rotation and thoracic
      torsion, between both groups. RESULTS: Before surgery, the main thoracic curve
      was 55.1 degrees (range, 47-66 degrees) for the ASF group and 52.5 degrees
      (range, 46-68 degrees ) for the PSF/TPS group (P = 0.16). Additionally, there was
      no difference in the pelvic tilt curves, thoracic kyphosis, lumbar lordosis, RH,
      or ARSD. However, there was a slightly greater preoperative thoracolumbar-lumbar
      (TL/L) curve (34.6 degrees versus 29.5 degrees , P = 0.04) and AVB-R (1.75 versus
      1.5, P = 0.003) in the ASF group. After surgery, an average of 6.5 levels (range,
      6-8) were fused in the ASF group, compared with 7.7 levels (range, 5-12) in the
      PSF/TPS group (P = 0.001) or 1.2 additional levels for PSF/TPS. At final
      postoperative follow-up, spontaneous pelvic tilt curve correction was greater in
      the ASF group (47% versus 35%), although this difference did not reach
      statistical significance (P = 0.07). For the main thoracic and TL/L curves, there
      was greater correction in the PSF/TPS group (62% versus 52%, P = 0.009; and 56%
      versus 41%, P = 0.03), respectively. Additionally, the PSF/TPS group demonstrated
      significantly greater RH correction (51% versus 26%, P = 0.005) and AVB-R ratio
      improvement (73% versus 32%, P < 0.0001). We also noted a trend towards increased
      correction of the ARSD in the PSF/TPS group (58% versus 32%, P = 0.07). Further,
      the postoperative thoracic kyphosis decreased 4.4 degrees in the PSF/TPS group
      (postop avg. 25.0 degrees ) and increased 5.7 degrees (average, 30.6 degrees ) in
      the ASF group (P = 0.04). CONCLUSIONS: In this curve-matched cohort of Lenke Type
      I curves, PSF with TPS provided superior instrumented correction of main thoracic
      curves and spontaneous correction of TL/L curves. Perhaps more importantly,
      PSF/TPS demonstrated improved correction of thoracic torsion and rotation as
      compared with ASF in terms of RH (P = 0.005) and AVB-R ratio (P= 0.0001), with
      only one additional spinal segment fused on average.

PMID- 16103857
TI  - The Modic classification: inter- and intraobserver error in clinical practice.
AB  - STUDY DESIGN: A reliability study of the Modic classification. OBJECTIVE: To
      determine the reliability and reproducibility of the Modic classification for
      lumbar vertebral marrow changes. SUMMARY OF BACKGROUND DATA: In 1988, Modic et al
      described two degenerative stages of vertebral marrow and endplate morphology.
      These were type 1 (inflammatory phase) and type 2 (a fatty phase). Later in 1988,
      he added a third variety: type 3 where there was marked sclerosis adjacent to the
      endplates. No formal reliability or reproducibility studies had been performed on
      this Modic classification. METHODS: This study involved five independent
      observers of differing spinal experience using the Modic classification to grade
      50 sagittal T1- and T2-weighted magnetic resonance imaging scans. The observers
      repeated the assessment at 3 weeks. Intra- and interobserver reliabilities were
      assessed using kappa statistics. RESULTS: There were 7 type 1, 40 type 2, 1 type
      3, and 2 normal levels. The individual intraobserver agreement was substantial or
      excellent with kappa values ranging from 0.71 to 1. The overall interobserver
      agreement was excellent with a kappa value of 0.85. There was complete agreement
      in 78% of the levels, a difference of one type in 14% and a difference of two or
      more in 8% of levels. The level of experience of the observer did not correlate
      with a better score. CONCLUSIONS: We have shown that the classification is both
      reliable and reproducible. It is simple and easy to apply for observers of
      varying clinical experience. We therefore recommend its use in clinical research
      and practice.

PMID- 16103858
TI  - Cord monitoring changes and segmental vessel ligation in the "at risk" cord
      during anterior spinal deformity surgery.
AB  - STUDY DESIGN: Retrospective analysis of all cases of anterior spinal deformity
      surgery that had intraoperative spinal cord monitoring (somatosensory-evoked
      potentials, SSEPs). OBJECTIVES: The prime purpose of this study was to determine
      the incidence of significant SSEP changes in patients undergoing anterior spinal
      deformity surgery. A secondary objective was to ascertain if patients with "cords
      at risk" were more likely to produce significant intraoperative SSEP changes and
      what proportion of these changes resulted in postoperative neurological deficit.
      SUMMARY OF BACKGROUND DATA: There is anecdotal evidence to suggest that patients
      with intraspinal abnormalities are at greater risk of postoperative neurological
      deficit after spinal deformity surgery. To date, there have been no studies
      detailing this risk and how it relates to the type of surgery performed. This is
      a question of increasing relevance with the modern trend towards more anterior
      scoliosis correction and instrumentation. Recent reports have suggested a low
      incidence of neurological complication with anterior deformity procedures. There
      is controversy as to whether SSEP monitoring is required for these anterior
      procedures and whether soft clamping of segmental vessels before their division
      is a necessary precaution. METHOD: This study is a chart review of all patients
      who had an anterior deformity operation between 1990 and 2001. Those patients who
      had a complete data set (preoperative magnetic resonance imaging scan, patient
      and procedural documentation, and adequate intraoperative SSEP traces) were
      included in this study. A significant SSEP change was correlated with the type of
      procedure performed, whether that patient had a "cord at risk" (CAR) and the
      degree of postoperative neurological deficit if present. RESULTS: During the
      study period, 871 patients underwent elective anterior spinal deformity surgery.
      Ninety five (11%) patients had intraspinal abnormalities on magnetic resonance
      imaging. From this group, 27 (3%) were termed CAR. Twenty six (3%) patients had
      significant change in the intraoperative SSEP monitoring. Seventeen (2% total)
      occurred in the CAR group and nine (1% of total) in the normal cord group. There
      were five patients (0.6%) with significant postoperative neurological deficits,
      four (0.5%) in the CAR group, and one (0.1%) in the normal cord group. These
      patients had also demonstrated changes in their SSEPs. The sensitivity of SSEP
      monitoring for the whole series was 100%, specificity 97.5%, the positive
      predictive value was 19% and the negative predictive value was 100%. The CAR
      group was significantly more likely to have significant SSEP changes during any
      operation and was more likely to have postoperative paresis. CONCLUSION: Patients
      with identified cords at risk should undergo spinal cord monitoring (SSEP) if
      they undergo anterior spinal deformity surgery. Soft clamping of segmental
      vessels is indicated with cord monitoring to prevent the risk of postoperative
      neurological sequelae.

PMID- 16103859
TI  - Magnetic resonance imaging study of the level of termination of the conus
      medullaris and the thecal sac: influence of age and gender.
AB  - STUDY DESIGN: Sequential study of magnetic resonance imaging (MRI) of the spine
      for assessing the level of termination of the conus medullaris (CMT) and thecal
      sac (TST). OBJECTIVES: To determine the variation in CMT and the TST as a
      function of age and gender in an adult population without spinal deformity and to
      investigate the relationship between CMT and TST. SUMMARY OF BACKGROUND DATA: It
      is generally accepted that the conus medullaris terminates in the lower third of
      L1; however, a wide range of values has been reported in cadaver studies as well
      as in MRI studies during life. There have been only a few reports on the
      influence of gender on the CMT, and the influence of age has not been studied at
      all. There have been few studies on the range of termination of the thecal sac,
      and the influence of age and gender remain unexplored. METHODS: We reviewed the 3
      mm sagittal MR images of 635 patients, including 297 women and 338 men, with a
      mean age of 49.43 years. The CMT and TST were located in relation to spinal
      levels and assigned numerical values ranging from 0 to 13. Parametric and
      nonparametric statistical tests were used for the data analysis. RESULTS: Mean
      CMT was at the level of the middle third of L1. The range span extended from the
      lower third of Th11 to the upper third of L3. The CMT displayed a small but
      significant positive correlation with age and with gender. Mean TST was at the
      level of the upper third of S2. The range extended from the lower third of L3 to
      the upper third of S5. The TST was not affected by gender, but age had an effect
      on TST. CONCLUSIONS: The CMT and TST displayed a wide range of values in our
      study. We detected small but systematic influences of gender and age on CMT and
      of age on TST, as well as a positive correlation between CMT and TST. These
      effects are small in amplitude, but they met all the criteria for statistical
      significance and have practical value for clinicians, as well as theoretical
      value for the medical and biologic community.

PMID- 16103860
TI  - Prognostic factors for low back pain in patients referred for physiotherapy:
      comparing outcomes and varying modeling techniques.
AB  - STUDY DESIGN: Data were derived from a randomized controlled trial on the (cost-)
      effectiveness of the implementation of the clinical guidelines on physiotherapy
      for low back pain in primary care. OBJECTIVES: To describe the course of low back
      pain in patients who are referred to physiotherapy, to identify clinically
      important prognostic factors on different outcomes, and to evaluate the influence
      of different statistical techniques in developing a prognostic model. SUMMARY OF
      BACKGROUND DATA: Several studies have aimed to identify prognostic factors for
      low back pain in primary care. These studies focused on different outcome
      measures and used various statistical techniques. METHODS: Primary outcomes were
      perceived recovery, improvement in pain, improvement in functioning, and presence
      of disabling low back pain at 3 and 12 months follow-up. Multivariate logistic
      regression analyses were performed for each outcome variable. Two cut-off points
      were used to determine significance with respect to the univariate analysis, and
      two selection methods were used to build the final multivariate models. The
      resulting prognostic models were compared. RESULTS: A total of 500 patients were
      included. Pain and disability reduced considerably in the first 3 months, but
      further reduction was only modest. Prognostic factors varied for different
      outcomes, but the duration of the current episode was included in all models
      generated. Varying the statistical techniques also resulted in a different
      prognostic model with some change to the amount of variance explained.
      CONCLUSIONS: A substantial proportion of patients still experienced some pain and
      disability at 12 months follow-up. The most stable predictor of prognosis in low
      back pain was the duration of the current episode. The choice of statistical
      method influenced the final model; however, changes in the explained variance
      were small.

PMID- 16103861
TI  - Classification of low back pain in primary care: using "bothersomeness" to
      identify the most severe cases.
AB  - STUDY DESIGN: Prospective inception cohort. OBJECTIVE: To investigate the
      validity and use of a single question on the bothersomeness of low back pain
      (LBP) as a method of classifying the severity of symptoms among patients seen in
      clinical practice. SUMMARY OF BACKGROUND DATA: There is no widely accepted method
      for classifying patients with nonspecific LBP in clinical practice. There have
      been no previous reports of the validity and use of a question on bothersomeness
      as a method of classifying patients with LBP. METHODS: Consecutive patients (30
      59 years old) with LBP consulting at 5 United Kingdom general practices (n =
      1464) were mailed a questionnaire after consultation and 6 months later.
      Construct validity was assessed by comparing baseline responses on the single
      bothersomeness question with pain, disability, general health, and psychologic
      health measures. The ability of bothersomeness to predict outcomes at 6 months
      was assessed against pain, disability, work absence, and health care use.
      RESULTS: A total of 935 patients (65%) completed baseline questionnaires. There
      were 776 (83%) patients who consented to enter the follow-up study, and 447
      returned the 6-month questionnaire. At baseline, bothersomeness correlated with
      pain, disability, and other measures (P < 0.001), and had 80% sensitivity (61%
      specificity) to detect people in the highest category of pain and disability.
      People with bothersome LBP at baseline evaluation had an increased risk of work
      absence or health care consultations for LBP 6 months later (relative risks 2.8
      and 1.9, respectively). CONCLUSIONS: There is evidence for the validity of a
      single bothersomeness question as a measure of LBP severity. It has the potential
      to provide a practical standard scheme for classifying patients with LBP in
      clinical practice. However, further work is needed to clarify its usefulness in a
      clinical setting.

PMID- 16103862
TI  - Radiation exposure to the surgeon during fluoroscopically assisted percutaneous
      vertebroplasty: a prospective study.
AB  - STUDY DESIGN: A prospective case control study design was conducted. OBJECTIVES:
      The purpose of the current study was to determine the intraoperative radiation
      hazard to spine surgeons by occupational radiation exposure during percutaneous
      vertebroplasty and possible consequences with respect to radiation protection.
      SUMMARY OF BACKGROUND DATA: The development of minimally invasive surgery
      techniques has led to an increasing number of fluoroscopically guided procedures
      being done percutaneously such as vertebroplasty, which is the percutaneous
      cement augmentation of vertebral bodies. METHODS: Three months of occupational
      dose data for two spine surgeons was evaluated measuring the radiation doses to
      the thyroid gland, the upper extremities, and the eyes during vertebroplasty.
      RESULTS: The annual risk of developing a fatal cancer of the thyroid is 0.0025%,
      which means a very small to small risk. The annual morbidity (the risk of
      developing a cancer including nonfatal ones) is 0.025%, which already means a
      small to medium risk. The dose for the eye lens was about 8% of the threshold
      dose to develop a radiation induced cataract (150 mSv); therefore, the risk is
      very low but not negligible. The doses measured for the skin are 10% of the
      annual effective dose limit (500 mSv) recommended by the ICRP (International
      Commission on Radiologic Protection); therefore, the annual risk for developing a
      fatal skin cancer is very low. CONCLUSION: While performing percutaneous
      vertebroplasty, the surgeon is exposed to a significant amount of radiation.
      Proper surgical technique and shielding devices to decrease potentially high
      morbidity are mandatory. Training in radiation protection should be an integral
      part of the education for all surgeons using minimally invasive radiologic-guided
      interventional techniques.

PMID- 16103863
TI  - The surgical management of primary tumorsof the spine: initial results of an
      ongoing prospective cohort study.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVES: To prospectively validate the
      application of appendicular surgical oncology principles to the treatment of
      primary bone tumors of the spine at a quaternary care spine center using local
      recurrence, survival, and health-related quality of life as outcome measures.
      SUMMARY OF BACKGROUND DATA: There is clear evidence that violating the margins of
      a sarcoma or other malignancy during surgical resection will risk local
      recurrence and diminish overall survival. Previous publications have
      retrospectively demonstrated this oncologically sound approach to spine tumor
      management to be internally valid. The external validity or limited
      generalizability has not been assessed. METHODS: Included were all patients who
      underwent en bloc surgical resection of a primary tumor of the spine between
      January 1994 and November 2003, at the authors' institution. Patients were
      uniformly staged before surgery and baseline demographic and surgical variables
      were recorded, as well as a cross-sectional evaluation of generic health-related
      quality of life. RESULTS: Twenty-six patients (12 males and 14 females) were
      eligible for the study. Average age was 42 (range 16 to 70). There were 19
      malignant tumors and 7 benign. There are 20 surviving patients with an average
      follow-up of 41.5 months (range 6 to 111 months), 15 of whom had malignant
      tumors. None of these patients have evidence of local recurrence, and one has
      evidence of systemic disease. The health-related quality of life, using the SF
      36, shows acceptable morbidity of these procedures (physical component summary =
      37.73 +/- 11.52, MCS = 51.69 +/- 9.54). CONCLUSIONS: Principles of wide surgical
      resection, commonly applied in appendicular oncology, can and should be used for
      the treatment of primary bone tumors of the spine with anticipated acceptable
      morbidity and satisfactory survival.

PMID- 16103864
TI  - Re: Mardjetko S, Albert T, Andersson G, et al. Spine/SRS Spondylolisthesis
      Summary Statement. Spine 2005;30:S3.

PMID- 16103865
TI  - Sildenafil (Revatio) for pulmonary arterial hypertension.
AB  - A second oral alternative to more invasive therapy.

PMID- 16103866
TI  - Duloxetine (Cymbalta) for diabetic neuropathic pain.
AB  - A selective serotonin and norepinephrine reuptake inhibitor approved for
      depression and now also for diabetic peripheral neuropathy.

PMID- 16103867
TI  - Drugs for head lice.

PMID- 16103868
TI  - Acetylcysteine (Acetadote) for acetaminophen overdosage.

PMID- 16103869
TI  - AmpliChip CYP450 test.

PMID- 16103871
TI  - Trashing the genome: the role of nucleases during apoptosis.
AB  - Two classes of nucleases degrade the cellular DNA during apoptosis. Cell
      autonomous nucleases cleave DNA within the dying cell. They are not essential for
      apoptotic cell death or the life of the organism, but they might affect the
      efficiency of the process. By contrast, waste-management nucleases are essential
      for the life of the organism. In post-engulfment DNA degradation, the DNA of
      apoptotic cells is destroyed in lysosomes of the cells that have phagocytosed the
      corpses. Waste-management nucleases also destroy DNA that is released into the
      extracellular compartment. Here, we describe the complex group of nucleases that
      are involved in DNA destruction during apoptotic cell death.

PMID- 16103872
TI  - Peroxisomal matrix protein import: the transient pore model.
AB  - Peroxisomes import folded, even oligomeric, proteins, which distinguishes the
      peroxisomal translocation machinery from the well-characterized translocons of
      other organelles. How proteins are transported across the peroxisomal membrane is
      unclear. Here, we propose a mechanistic model that conceptually divides the
      import process into three consecutive steps: the formation of a translocation
      pore by the import receptor, the ubiquitylation of the import receptors, and pore
      disassembly/ receptor recycling.

PMID- 16103873
TI  - The molecular repertoire of the 'almighty' stem cell.
AB  - Stem cells share the defining characteristics of self-renewal, which maintains or
      expands the stem-cell pool, and multi-lineage differentiation, which generates
      and regenerates tissues. Stem-cell self-renewal and differentiation are
      influenced by the convergence of intrinsic cellular signals and extrinsic
      microenvironmental cues from the surrounding stem-cell niche, but the specific
      signals involved are poorly understood. Recently, several studies have sought to
      identify the genetic mechanisms that underlie the stem-cell phenotype. Such a
      molecular road map of stem-cell function should lead to an understanding of the
      true potential of stem cells.

PMID- 16103874
TI  - Fen1 is induced p53 dependently and involved in the recovery from UV-light
      induced replication inhibition.
AB  - Mouse embryonic fibroblasts (MEFs) that lack p53 are hypersensitive to the
      cytotoxic and genotoxic effect of ultraviolet (UV-C) light. They also display a
      defect in the recovery from UV-C-induced DNA replication inhibition. An enzyme
      involved in processing stalled DNA replication forks is flap endonuclease 1
      (Fen1). Gene expression profiling of UV-C-irradiated MEFs revealed fen1 to be
      upregulated, which was confirmed by RT-PCR and Western blot experiments.
      Increased Fen1 levels upon UV-C exposure are due to transcriptional activation,
      as revealed by inhibitor studies. Fen1 induction was dose- and time-dependent; it
      occurred on protein level already 3 h after irradiation. Induction of Fen1 by UV
      C requires p53 since it was observed in p53 wild-type (wt) but not in p53 null
      (p53-/-) fibroblasts. Fen1 upregulation paralleled the increase in p53 protein
      level in replicating wt cells, whereas in nonreplicating cells both Fen1 and p53
      were not induced by UV-C. The mouse fen1 promoter was cloned and shown to harbor
      a p53 consensus sequence to which p53 binds. In cotransfection experiments, p53
      stimulated the expression of a fen1 promoter-reporter construct. Transgenic
      expression of Fen1 in p53 null cells attenuated UV-C light-induced DNA
      replication inhibition, supporting the hypothesis that Fen1 induction is involved
      in the recovery of cells from DNA damage.

PMID- 16103875
TI  - Drosophila caliban, a nuclear export mediator, can function as a tumor suppressor
      in human lung cancer cells.
AB  - We previously showed that the Drosophila DNA binding homeodomain of Prospero
      included a 28 amino-acid sequence (HDA) that functions as a nuclear export
      signal. We describe here the identification of a protein we named Caliban, which
      can directly interact with the HDA. Caliban is homologous to human Sdccag1, which
      has been implicated in colon and lung cancer. Here we show that Caliban and
      Sdccag1 are mediators of nuclear export in fly and human cells, as interference
      RNA abrogates export of EYFP-HDA in normal fly and human lung cells. Caliban
      functions as a bipartite mediator nuclear export as the carboxy terminus binds
      HDA and the amino terminus itself functions as an NES, which directly binds the
      NES receptor Exportin. Finally, while non-cancerous lung cells have functional
      Sdccag1, five human lung carcinoma cell lines do not, even though Exportin still
      functions in these cells. Expression of fly Caliban in these human lung cancer
      cells restores EYFP-HDA nuclear export, reduces a cell's ability to form colonies
      on soft agar and reduces cell invasiveness. We suggest that Sdccag1 inactivation
      contributes to the transformed state of human lung cancer cells and that Caliban
      should be considered a candidate for use in lung cancer gene therapy.

PMID- 16103876
TI  - Mnt transcriptional repressor is functionally regulated during cell cycle
      progression.
AB  - The Myc/Max/Mad network of transcription factors regulates cell proliferation,
      differentiation, and transformation. Similar to other proteins of the network,
      Mnt forms heterodimers with Max and binds CACGTG E-Box elements. Transcriptional
      repression by Mnt is mediated through association with mSin3, and deletion of the
      mSin3-interacting domain (SID) converts Mnt to a transcriptional activator. Mnt
      is coexpressed with Myc in proliferating cells and has been suggested to be a
      modulator of Myc function. We report that Mnt is expressed both in growth
      arrested and proliferating mouse fibroblasts and is phosphorylated when resting
      cells are induced to re-enter the cell cycle. Importantly, the interaction
      between Mnt and mSin3 is disrupted upon serum stimulation resulting in decreased
      Mnt-associated HDAC activity. Furthermore, we demonstrate that Mnt binds and
      recruits mSin3 to the Myc target gene cyclin D2 in quiescent mouse fibroblasts.
      Interference with Mnt expression by RNAi resulted in upregulation of cyclin D2
      expression in growth-arrested fibroblasts, supporting the view that Mnt represses
      cyclin D2 transcription in quiescent cells. Our data suggest a model in which
      phosphorylation of Mnt at cell cycle entry results in disruption of Mnt-mSin3
      HDAC1 interaction, which allows induction of Myc target genes by release of Mnt
      mediated transcriptional repression.

PMID- 16103877
TI  - Rituximab (chimeric anti-CD20) sensitizes B-NHL cell lines to Fas-induced
      apoptosis.
AB  - Rituximab (chimeric anti-CD20 monoclonal antibodies) is currently being used in
      the treatment of B non-Hodgkin's lymphoma (NHL). We have recently reported that
      rituximab triggers and modifies various intracellular signaling pathways in NHL B
      cell lines, resulting in reverting the chemoresistant phenotype to a sensitive
      phenotype. This study investigated whether rituximab also modifies intracellular
      signaling pathways resulting in the sensitization of NHL cells to Fas-induced
      apoptosis. Treatment of the Fas-resistant NHL cell lines (2F7, Ramos and Raji)
      with rituximab sensitized the cells to CH-11 (FasL agonist mAb)-induced apoptosis
      and synergy was achieved. Fas expression was upregulated by rituximab as early as
      6 h post-treatment as determined by flow cytometry, reverse transcriptase
      polymerase chain reaction and Western blot. Rituximab inhibited both the
      expression and activity of the transcription repressor Yin-Yang 1 (YY1) that
      negatively regulates Fas transcription. Inhibition of YY1 resulted in the
      upregulation of Fas expression and sensitization of the tumor cells to CH-11
      induced apoptosis. The downregulation of YY1 expression was the result of
      rituximab-induced inhibition of both the p38 mitogen-activated protein kinase
      (MAPK) signaling pathway and constitutive nuclear factor kappa of B cells (NF
      kappaB) activity. The involvement of NF-kappaB and YY1 in the regulation of Fas
      expression was corroborated by the use of Ramos cells with a dominant-active
      inhibitor of NF-kappaB (Ramos IkappaB-estrogen receptor (ER) mutant) and by
      silencing YY1 with YY1 siRNA, respectively. Further, the role of rituximab
      mediated inhibition of the p38 MAPK/NF-kappaB/YY1 pathway in the regulation of
      Fas and sensitization to CH-11-induced apoptosis was validated by the use of
      specific chemical inhibitors of this pathway and which mimicked rituximab
      mediated effects. These findings provide a novel mechanism of rituximab-mediated
      activity by sensitizing NHL cells to Fas-induced apoptosis.

PMID- 16103878
TI  - ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric
      cancers by homozygous deletion or aberrant promoter hypermethylation.
AB  - Array-based comparative genomic hybridization (CGH-array) has a powerful
      potential for high-throughput identification of genetic aberrations in cell
      genomes. We identified a homozygous loss of ADAM23 (2q33.3) in the course of a
      program to screen a panel of gastric cancer (GC) cell lines (1/32, 3.1%) for
      genomic copy-number aberrations using our custom-made CGH-array. Infrequent
      homozygous deletion of ADAM23 was also seen in primary gastric tumors (1/39,
      2.6%). ADAM23 mRNA was expressed in normal stomach tissue, but not in the
      majority of GC cell lines without homozygous deletion of this gene. Expression of
      ADAM23 mRNA was restored to gene-silenced GC cells after treatment with 5-aza 2'
      deoxycytidine. The methylation status of the ADAM23 CpG island, which showed
      promoter activity, correlated inversely with its expression. Methylation of this
      CpG island was observed both in GC cell lines and in primary GC tissues; in
      primary tumors with a hypermethylated CpG island, expression of ADAM23 was lower
      than in adjacent noncancerous tissues. Moreover, restoration of ADAM23 in GC
      cells reduced their numbers in colony-formation assays. These results suggest
      that genetic or epigenetic silencing by hypermethylation of the ADAM23 CpG-rich
      promoter region leads to loss of ADAM23 function, which may be a factor in
      gastric carcinogenesis.

PMID- 16103879
TI  - Induction of p21(WAF1/CIP1) by human synovial sarcoma-associated chimeric
      oncoprotein SYT-SSX1.
AB  - Oncogenic protein provokes cell cycle arrest termed premature senescence. In this
      process Ras has been known to induce cyclin-dependent kinase inhibitor (CKI)
      p16(INK4A) in primary fibroblasts. Here, we present a novel finding that human
      chimeric oncoprotein SYT-SSX1 induces CKI p21(WAF1/CIP1) (p21) for suppression of
      cell growth. In human synovial sarcoma cell lines, the expression levels of p21
      were high and the transcriptional activity of the p21 gene promoter was
      significantly elevated. The transient expression of SYT-SSX1-induced activation
      of the p21 gene promoter in human diploid fibroblasts. The N-terminus deletion
      form of SYT-SSX1, which failed to bind to hBRM one of the chromatin remodeling
      factors, preserved the p21 induction ability. This effect of SYT-SSX1 was similar
      in extent in both wild-type and p53-deficient HCT116 cell lines. Furthermore, the
      introduction of mutation in Sp1/Sp3 binding sites of the p21 gene promoter
      abolished the SYT-SSX1-induced transcriptional activity of its promoter. In SW13
      cells, the stable expression of SYT-SSX1 suppressed cell growth in culture. These
      results suggest that SYT-SSX1 is able to induce p21 in a manner independent on
      hBRM and p53 but dependent on Sp1/Sp3.

PMID- 16103880
TI  - A kinase-dependent role for EphA2 receptor in promoting tumor growth and
      metastasis.
AB  - Receptor tyrosine kinases of the Eph family are upregulated in several different
      types of cancer. One family member in particular, the EphA2 receptor, has been
      linked to breast, prostate, lung and colon cancer, as well as melanoma. However,
      mechanisms by which EphA2 contributes to tumor progression are far from clear. In
      certain tumor cell lines, EphA2 receptor is underphosphorylated, raising the
      question of whether ligand-induced receptor phosphorylation and its kinase
      activity play a role in oncogenesis. To test directly the role of EphA2 receptor
      phosphorylation/kinase activity in tumor progression, we generated EphA2 receptor
      variants that were either lacking the cytoplasmic domain or carrying a point
      mutation that inhibits its kinase activity. Expression of these EphA2 mutants in
      breast cancer cells resulted in decreased tumor volume and increased tumor
      apoptosis in primary tumors. In addition, the numbers of lung metastases were
      significantly reduced in both experimental and spontaneous metastasis models.
      Reduced tumor volume and metastasis are not due to defects in tumor angiogenesis,
      as there is no significant difference in tumor vessel density between wild-type
      tumors and tumors expressing EphA2-signaling-defective mutants. In contrast,
      tumor cells expressing the EphA2 mutants are defective in RhoA GTPase activation
      and cell migration. Taken together, these results suggest that receptor
      phosphorylation and kinase activity of the EphA2 receptor, at least in part,
      contribute to tumor malignancy.

PMID- 16103881
TI  - Prediction of clinical outcome and biological characterization of neuroblastoma
      by expression profiling.
AB  - Neuroblastoma is a common childhood tumor comprising cases with rapid disease
      progression as well as spontaneous regression. Although numerous prognostic
      factors have been identified, risk evaluation in individual patients remains
      difficult. To define a reliable prognostic predictor and gene signatures
      characteristic of biological subgroups, we performed mRNA expression profiling of
      68 neuroblastomas of all stages. Expression data were analysed using support
      vector machines (SVM-rbf), prediction analysis of microarrays (PAM), k-nearest
      neighbors (k-NN) algorithms and multiple decision trees. SVM-rbf performed best
      of all methods, and predicted recurrence of neuroblastoma with an accuracy of 85%
      (sensitivity 77%, specificity 94%). PAM identified a classifier of 39 genes
      reliably predicting outcome with an accuracy of 80%. In comparison, conventional
      risk stratification based on stage, age and MYCN-status only reached a predictive
      accuracy of 64%. Kaplan-Meier analysis using the PAM classifier indicated a 5
      year survival of 20 versus 78% for patients with unfavorably versus favorably
      predicted neuroblastomas, respectively (P = 0.0001). Significance analysis of
      microarrays (SAM) identified additional genes differentially expressed among
      subgroups. MYCN-amplification and high expression of NTRK1/TrkA demonstrated a
      strong association with specific gene expression patterns. Our data suggest that
      microarray-derived data in addition to traditional clinical factors will be
      useful for risk assessment and defining biological properties of neuroblastoma.

PMID- 16103882
TI  - Basic fibroblast growth factor suppresses p53 activation in the neoplastic cells
      of a proportion of patients with chronic lymphocytic leukaemia.
AB  - p53 is the most frequently inactivated gene in human cancers, reflecting its
      pivotal role in maintaining genomic integrity. The present study was conducted to
      explore the possibility that tumour cells with no intrinsic defects of the p53
      pathway might nevertheless acquire p53 dysfunction through extrinsic suppression
      of the pathway by microenvironmental factors. Neoplastic cells from patients with
      chronic lymphocytic leukaemia (CLL) were cultured in the presence or absence of
      basic fibroblast growth factor (bFGF) and exposed to ionizing radiation (IR) to
      induce p53 accumulation. bFGF is greatly increased in the plasma of CLL patients
      and can suppress p53 activation in some experimental models. IR induced a marked
      increase in p53 levels in 28 samples from 24 patients. bFGF inhibited IR-induced
      p53 accumulation to some extent in most of these samples and by more than 50% in
      seven samples from seven patients. Suppression of p53 activation by bFGF was
      frequently but not always accompanied by upregulation of the p53-inhibitory
      protein MDM2 and/or phosphorylation of MDM2 at serine 166, and was associated
      with impaired transcriptional activation of the p53 target gene p21. These
      observations provide the first demonstration in human cancer cells that the p53
      pathway can be suppressed by factors in the tumour-cell microenvironment.

PMID- 16103883
TI  - Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize
      progressive astrocytoma.
AB  - Astrocytoma is the most common type of brain cancer constituting more than half
      of all brain tumors. With an aim to identify markers describing astrocytoma
      progression, we have carried out microarray analysis of astrocytoma samples of
      different grades using cDNA microarray containing 1152 cancer-specific genes.
      Data analysis identified several differentially regulated genes between normal
      brain tissue and astrocytoma as well as between grades II/III astrocytoma and
      glioblastoma multiforme (GBM; grade IV). We found several genes known to be
      involved in malignancy including Achaete-scute complex-like 1 (Drosophila)
      (ASCL1; Hash 1). As ASCL has been implicated in neuroendocrine, medullary thyroid
      and small-cell lung cancers, we chose to examine the role of ASCL1 in the
      astrocytoma development. Our data revealed that ASCL1 is overexpressed in
      progressive astrocytoma as evidenced by increased levels of ASCL1 transcripts in
      85.71% (6/7) of grade II diffuse astrocytoma (DA), 90% (9/10) of grade III
      anaplastic astrocytoma (AA) and 87.5% (7/8) of secondary GBMs, while the majority
      of primary de novo GBMs expressed similar to or less than normal brain levels
      (66.67%; 8/12). ASCL1 upregulation in progressive astrocytoma is accompanied by
      inhibition of Notch signaling as seen by uninduced levels of HES1, a
      transcriptional target of Notch1, increased levels of HES6, a dominant-negative
      inhibitor of HES1-mediated repression of ASCL1, and increased levels of Notch
      ligand Delta1, which is capable of inhibiting Notch signaling by forming
      intracellular Notch ligand autonomous complexes. Our results imply that
      inhibition of Notch signaling may be an important early event in the development
      of grade II DA and subsequent progression to grade III AA and secondary GBM.
      Furthermore, ASCL1 appears to be a putative marker to distinguish primary GBM
      from secondary GBM.

PMID- 16103884
TI  - Ras and Myc can drive oncogenic cell proliferation through individual D-cyclins.
AB  - D-type cyclins serve as cell cycle recipients of several oncogenic pathways. The
      specific sequences of the promoters of the cyclin D genes are thought to render
      particular D-cyclins responsive to specific oncogenic pathways. For instance, the
      Ras oncogene was postulated to signal through cyclin D1, while Myc can impact the
      cell cycle machinery by transcriptionally upregulating cyclin D2. In the current
      study we engineered mouse fibroblasts to express only cyclin D1, only D2, or only
      D3. These 'single-cyclin' cells allowed us to rigorously test the ability of
      cyclin D1, D2, or D3, when expressed on their own, to serve as recipients of the
      Ras- and Myc-driven oncogenic pathways. We found that each of the D-cyclins was
      sufficient to drive oncogenic proliferation of mouse fibroblasts. This, together
      with our recent observations that cells lacking all three D-cyclins show greatly
      reduced susceptibility to the oncogenic action of Ras and Myc, reveals that the
      Ras and Myc oncogenes can impact the core cell cycle machinery through all three
      D-cyclins.

PMID- 16103885
TI  - Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic
      lesions.
AB  - Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all
      solid tumours. Both the late clinical presentation of patients, due to lack of
      early symptoms, as well as the rapid and aggressive course of the disease
      contribute to the extremely high mortality of this malignancy. Recently, a
      multistep progression model for PDAC integrating morphological, clinical and
      molecular evidence has been proposed. Putative precursor lesions, termed
      pancreatic intraepithelial neoplasia (PanIN), are classified into three different
      grades (PanIN-1 through -3) based on the degree of cellular atypia they display.
      We have conducted large-scale expression profiling analyses of microdissected
      cells from normal pancreatic ducts, PanINs of different grades and PDACs using
      whole-genome oligonucleotide microarrays. Verification of hybridisation results
      for selected genes was performed using quantitative real-time PCR and
      immunohistochemical analyses on PanIN tissue microarrays. Comparison of the
      expression profiles demonstrated that the greatest changes in gene expression
      occur between PanIN stages 1B and 2, suggesting that PanIN-2 may represent the
      first truly preneoplastic stage in PDAC progression. Our results identify a large
      number of potential target genes for the development of novel molecular
      diagnostic and therapeutic tools for the prevention and early diagnosis of PDAC
      and provide novel insights into the pathophysiological mechanisms involved in
      tumour progression in the pancreas.

PMID- 16103886
TI  - The hScrib/Dlg apico-basal control complex is differentially targeted by HPV-16
      and HPV-18 E6 proteins.
AB  - The E6 proteins of the high-risk Human papillomaviruses (HPV) types have a well
      documented ability to target certain cellular proteins for ubiquitin-mediated
      degradation via the proteasome. Previous studies have shown that E6 proteins
      interact differently with different target proteins, and that the viral proteins,
      depending upon the target, may recruit diverse cellular ubiquitin-protein
      ligases. In this study, we have examined the abilities of E6 proteins from HPV-16
      and HPV-18 to interact with and induce the degradation of two PDZ domain
      containing targets, Dlg and hScrib. We have also mapped the binding site of E6 on
      hScrib and shown that the interaction of E6 with hScrib is distinct from its
      interactions with other PDZ domain-containing targets. This is reflected in the
      efficiency with which the two viral E6 proteins can inhibit hScrib's suppression
      of cell transformation.Dlg and hScrib have complementary activities in the
      control of epithelial cell polarity and the fact that both are targeted by high
      risk HPV E6 proteins underlines their importance. Our finding that they are each
      targeted differently by HPV-16 and HPV-18 E 6 s suggests that the two viruses are
      subjected to somewhat different constraints and provides a possible explanation
      for the apparent redundancy in targeting both parts of this important control
      mechanism.

PMID- 16103887
TI  - Influence of serotonin transporter gene polymorphisms on cognitive decline and
      cognitive abilities in a nondemented elderly population.
AB  - Dysfunction of the serotonergic pathway disrupts normal cognitive functioning and
      is believed to be the underlying basis for a variety of psychiatric disorders.
      Two functional polymorphisms within the serotonin transporter (SLC6A4) gene
      (promoter 44 bp insertion/deletion (HTTLPR) and an intron two 16 or 17 bp
      variable number tandem repeat (VNTR2)) have been extensively studied in
      psychiatric conditions but not in the cognitive functioning of normal
      individuals. We have investigated these two polymorphisms for association with
      both the level of cognitive abilities and their decline with age using a cohort
      consisting of over 750 elderly nondemented individuals with a follow-up of up to
      15 years. We found that volunteers homozygous for the VNTR2 12 allele had a
      faster rate of decline for all cognitive tests. This reached significance for
      both tests of fluid intelligence (novel problem solving) (AH1 P=0.002, AH2
      P=0.014), the test of semantic memory (P=0.010) and general cognitive ability
      (P=0.006). No association was observed between the HTTLPR polymorphism and the
      rate of cognitive decline when analysed either independently or in combination
      with the VNTR2 polymorphism based on their influence on expression in vitro. No
      associations were observed between the two polymorphisms and the baseline level
      of cognitive abilities. This is only the second gene that has been reported to
      regulate the rate of cognitive decline in nondemented individuals and may be a
      target for the treatment of cognitive impairment in the elderly.

PMID- 16103888
TI  - A haplotype within the DISC1 gene is associated with visual memory functions in
      families with a high density of schizophrenia.
AB  - We have previously reported evidence of linkage and association between markers
      on 1q42 and schizophrenia in a study sample of 498 multiply affected Finnish
      nuclear families, leading to the recent identification of four significantly
      associated haplotypes that specifically implicate the Translin-Associated Factor
      X (TRAX) and Disrupted in Schizophrenia 1 and 2 (DISC1 and DISC2) genes in the
      genetic etiology of schizophrenia. Previously, the DISC genes were found to be
      disrupted by a balanced translocation (1;11)(q42.1;q14.3) that cosegregated with
      schizophrenia and related disorders in a large Scottish pedigree. Interestingly,
      we also reported earlier suggestive linkage between endophenotypic quantitative
      traits of visual and verbal memory and microsatellite markers in close proximity
      to TRAX/DISC, on 1q41. Here, we tested if the identified allelic haplotypes of
      TRAX/DISC would be associated with visual and/or verbal memory function
      impairments that are known to aggregate with schizophrenia in families. One
      haplotype of DISC1, HEP3, displayed association with poorer performance on tests
      assessing short-term visual memory and attention. Analysis of affected and
      unaffected offspring separately revealed that both samples contribute to the
      observed association to visual working memory. These results provide genetic
      support to the view that the DISC1 gene contributes to sensitivity to
      schizophrenia and associated disturbances and affects short-term visual memory
      functions. This finding should stimulate studies aiming at the molecular
      characterization of how the specific alleles of DISC1 affect the visual memory
      functions and eventually participates in the development of schizophrenia.

PMID- 16103889
TI  - A dopamine transporter mutation associated with bipolar affective disorder causes
      inhibition of transporter cell surface expression.
AB  - The dopamine transporter (DAT) plays a crucial role in dopaminergic
      neurotransmission as it clears the extracellular space of dopamine (DA) and thus
      controls the concentration of active neurotransmitter. Genetic association
      studies have reported a variable number of tandem repeat polymorphisms in the 3'
      noncoding region of the DAT gene implicating this protein in the development of
      various psychiatric disorders. In a sample of bipolar patients, two rare missense
      substitutions (A559V and E602G) have been identified, one of which (E602G) was
      inherited by the patient from her affected father. None of these mutations had
      been identified in any control subjects of this survey. Using a heterologous
      cellular expression system, we have analysed possible consequences of these
      mutations on functional properties of the encoded DAT protein. DA transport
      measurements and antagonist binding revealed that the A559V mutant protein is
      fully functional, whereas the E602G mutant is not. Further analyses by confocal
      microscopy showed that the E602G protein is transcribed and translated but not
      delivered to the cell surface. Taken together, our results suggest that this
      missense mutation has functional consequences thus supporting the need to screen
      larger samples of patients and their relatives for this rare but bipolar disorder
      associated mutation in the DAT gene.

PMID- 16103890
TI  - Autism and the serotonin transporter: the long and short of it.
AB  - Autism is a neurodevelopmental disorder manifesting early in childhood. Some
      symptoms of autism are alleviated by treatment with selective serotonin reuptake
      inhibitors, which are known to interact with the serotonin transporter. Moreover,
      variation in the gene that encodes the transporter (SLC6A4), especially the
      HTTLPR locus, is known to modulate its expression. It is natural, therefore, to
      evaluate whether this variation plays a role in liability to autism. We
      investigated the impact of alleles at HTTLPR and three other loci in SLC6A4 by
      using a large, independent family-based sample (390 families, 1528 individuals)
      from the NIH Collaborative Programs of Excellence in Autism (CPEA) network.
      Allele transmissions to individuals diagnosed with autism were biased only for
      HTTLPR, both for the narrow diagnosis of autism (P=0.035) and for the broader
      diagnosis of autism spectrum (P=0.007). The short allele of HTTLPR was
      significantly overtransmitted. Investigation of haplotype transmissions suggested
      that, in our data, biased transmission was only due to HTTLPR. With respect to
      this locus, there are now seven of 12 studies reporting significant transmission
      bias of HTTLPR alleles, a noteworthy result in itself. However, the studies with
      significant findings are almost equally divided between overtransmission of short
      and overtransmission of long alleles. We place our results within this extremely
      heterogeneous field of studies. Determining the factors influencing the
      relationship between autism phenotypes and HTTLPR variation, as well as other
      loci in SLC6A4, could be an important advance in our understanding of this
      complex disorder.

PMID- 16103891
TI  - Obesity intervention in persons with spinal cord injury.
AB  - STUDY DESIGN: A single group uncontrolled trial. OBJECTIVES: Despite widespread
      emphasis on the obesity-related health risks in persons with spinal cord injury
      (SCI), limited research has been carried out to intervene in this problem. This
      study was conducted to assess the initial effectiveness of a weight loss program
      on various health outcomes in persons with SCI. SETTING: A rehabilitation center
      in Birmingham, Alabama, United States. METHODS: A total of 16 individuals with
      chronic SCI who were overweight or obese participated in a weight management
      program that consisted of 12 weekly classes, covering nutrition, exercise, and
      behavior modification. Various outcomes were examined over a 6-month period
      (baseline, week 12, and week 24), including body composition measured by dual
      energy X-ray absorptiometry, physiologic measures, diet behavior, and
      psychosocial and physical functioning. Of these, 13 participants returned for the
      week 24 follow-up. RESULTS: Weight loss averaged 3.5+/-3.1 kg (3.8% of the
      initial weight) at week 12 and 2.9+/-3.7 kg (3.0% of the initial weight) at week
      24. There was a significant reduction from baseline values at weeks 12 and 24 in
      body mass index, anthropometric measurements, and fat mass and improvement in
      diet behavior and psychosocial and physical functioning, while lean mass and
      blood albumin and hemoglobin levels were maintained. A correlation analysis
      showed that a greater weight loss was importantly (r>0.4) associated with a
      greater reduction in total cholesterol at weeks 12 and 24 and in systolic and
      diastolic blood pressure at week 24. Several factors were important (r>0.4 or r<
      0.4) in determining the success in weight loss, including age, race, marital and
      employment status, family history of overweight/obesity, level and duration of
      injury, and cholesterol level at baseline. CONCLUSIONS: This is the first
      demonstration that a carefully planned program with time-calorie displacement
      diet is effective for overweight/obese individuals with SCI to lose weight
      without compromising total lean mass and overall health. It provides foundation
      for a future large clinical trial for weight loss of persons with SCI or other
      spinal cord dysfunction.

PMID- 16103892
TI  - Antitumor effect of antisense ODC adenovirus on human prostate cancer cells.
AB  - Ornithine decarboxylase (ODC), the first enzyme of polyamine biosynthesis, was
      found to increase in cancer cells, especially prostate cancers. Some
      chemotherapeutic agents aimed to decrease ODC expression showed inhibitory
      effects on cancer cells. In this study, we examined the effect of adenoviral
      transduced antisense ODC on prostate cancer cells. An adenovirus carrying
      antisense ODC (rAd-ODC/Ex3as) was infected to prostate cancer cells PC-3 and
      LNCap. Expression of ODC and concentration of polyamines in cells were determined
      by Western blotting and HPLC. MTT (3-(4,5-methylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide) assay was used to analyze the effect on cell growth. Cell
      cycle was evaluated by FCM and cellular invasion by Matrigel invasion assay. A
      nude mouse xenograft model was used to examine tumorigenicity. Expression of ODC
      in PC-3 and LNCap cells were reduced to 45 and 59%, and three polyamines were
      also decreased by the rAd-ODC/Ex3as treatment. Consequently, cell growth was
      substantially inhibited and cell cycle arrested at G1 phase. Matrigel invasion
      assay showed relatively low invasion. Marked suppression of tumor formation was
      observed in the xenograft model. This study suggests that rAd-ODC/Ex3as has the
      antitumor effect on the human prostate cancer cells.

PMID- 16103893
TI  - Fetal, infant and childhood growth: relationships with body composition in
      Brazilian boys aged 9 years.
AB  - BACKGROUND: Early growth rate has been linked to later obesity categorised by
      body mass index (BMI), but the development of body composition has rarely been
      studied. METHODS: We tested the hypotheses that (1) birthweight and weight gain
      in (2) infancy or (3) childhood are associated with later body composition, in
      172 Brazilian boys followed longitudinally since birth. Growth was assessed using
      measurements of weight and height at birth, 6 months, and 1 and 4 y. Measurements
      at 9 y comprised height, weight and body composition using foot-foot impedance.
      RESULTS: Birthweight was associated with later height and lean mass (LM), but not
      fatness. Weight gain 0-6 months was associated with later height and LM, and with
      obesity prevalence according to BMI, but not with fatness. Weight gain 1-4 y was
      associated with later fatness and LM. Weight gain 4-9 y was strongly associated
      with fatness but not LM. Early growth rate did not correlate positively with
      subsequent growth rate. CONCLUSIONS: Early rapid weight gain increased the risk
      of later obesity, but not through a direct effect on fatness. Childhood weight
      gain remained the dominant risk factor for later obesity. The reported link
      between early growth and later obesity may be due partly to hormonal programming,
      and partly to the contribution of LM to obesity indices based on weight and
      height. Whether our findings apply to other populations requires further
      research.

PMID- 16103894
TI  - Changes in body weight and health-related quality-of-life in the older adult
      population.
AB  - BACKGROUND: No other study has ascertained the short-term impact of weight change
      on health-related quality-of-life (HRQL) on a national sample of older adults.
      OBJECTIVE: To examine the relationship between change in body weight and HRQL
      among the older adult population. METHODS: We carried out a prospective study
      from 2001 to 2003 of a cohort of 2364 persons, representative of the
      noninstitutionalized Spanish population aged 60 y and over. Weight changes during
      the period 2001-2003 were self-reported, and HRQL in 2003 was measured with the
      SF-36 questionnaire. Analyses adjusted for the principal confounders. RESULTS:
      Among nonobese women (body mass index (BMI) 18.5-29.9 kg/m(2)), and compared to
      those who underwent no important weight change, weight loss was associated with a
      clinically significant worsening in the role-physical, vitality, and social
      functioning SF-36 scales. Among obese women (BMI> or =30 kg/m(2)), weight gain
      led to a reduction in HRQL for four of the eight SF-36 scales, while weight loss
      was associated with worse scores in role-emotional and mental health scales.
      Results were usually similar for men, though of lower magnitude. In both sexes,
      weight change was associated with a reduction of over 5 points on several
      physical and mental scales of the SF-36, which indicates a clinically relevant
      worsening in HRQL. CONCLUSION: Weight change is associated with worse HRQL among
      the older adults, principally women. From the stance of HRQL, it is desirable to
      prevent weight gain, especially among the obese, and weight loss, especially
      among the nonobese.

PMID- 16103895
TI  - Linking pathway gene expressions to the growth inhibition response from the
      National Cancer Institute's anticancer screen and drug mechanism of action.
AB  - Novel strategies are proposed to quantitatively analyze and relate biological
      pathways to drug responses using gene expression and small-molecule growth
      inhibition data (GI(50)) derived from the National Cancer Institute's 60 cancer
      cells (NCI(60)). We have annotated groups of drug GI(50) responses with pathways
      defined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta, and
      functional categories defined by Gene Ontology (GO), through correlations between
      pathway gene expression patterns and drug GI(50) profiles. Drug-gene-pathway
      relationships may then be utilized to find drug targets or target-specific drugs.
      Significantly correlated pathways and the gene products involved represent
      interesting targets for further exploration, whereas drugs that are significantly
      correlated with only certain pathways are more likely to be target specific.
      Separate pathway clustering finds that pathways engaged in the same biological
      process tend to have similar drug correlation patterns. The biological and
      statistical significances of our method are established by comparison to known
      small-molecule inhibitor-gene target relationships reported in the literature and
      by standard randomization procedures. The results of our pathway, gene expression
      and drug-induced growth inhibition associations, can serve as a basis for
      proposing testable hypotheses about potential anticancer drugs, their targets,
      and mechanisms of action.

PMID- 16103896
TI  - An association study of 43 SNPs in 16 candidate genes with atorvastatin response.
AB  - Variation in individual response to statin therapy has been widely studied for a
      potential genetic component. Multiple genes have been identified as potential
      modulators of statin response, but few study findings have replicated. To further
      examine these associations, 2735 individuals on statin therapy, half on
      atorvastatin and the other half divided among fluvastatin, lovastatin,
      pravastatin and simvastatin were genotyped for 43 SNPs in 16 genes that have been
      implicated in statin response. Associations with low-density lipoprotein
      cholesterol (LDL-C) lowering, total cholesterol lowering, HDL-C elevation and
      triglyceride lowering were examined. The only significant associations with LDL-C
      lowering were found with apoE2 in which carriers of the rare allele who took
      atorvastatin lowered their LDL-C by 3.5% more than those homozygous for the
      common allele and with rs2032582 (S893A in ABCB1) in which the two groups of
      homozygotes differed by 3% in LDL-C lowering. These genetic effects were smaller
      than those observed with the demographic variables of age and gender. The
      magnitude of all the differences found is sufficiently small that genetic data
      from these genes should not influence clinical decisions on statin
      administration.

PMID- 16103897
TI  - Clinical response to morphine in cancer patients and genetic variation in
      candidate genes.
AB  - Morphine is the analgesic of choice for moderate to severe cancer pain; however,
      10-30% of patients do not tolerate morphine. This study evaluated genetic
      variation in the mu-opioid receptor, betaarrestin2, stat6 and uridine diphosphate
      glucuronysltransferase 2B7 (UGT2B7) genes, in patients who responded to morphine
      vs those who were switched to alternative opioids. We prospectively recruited and
      genotyped 162 Caucasian patients (117 controls, 39 switchers). Switchers, were
      more likely to carry the common allele at 1182 G/A, 5864 G/A, 8622T/C and 11143
      G/A in the betaarrestin2 gene (P = 0.021, 0.043, 0.013, 0.043, respectively).
      Switchers had increased carriage of the T allele (-1714 C/T) and a significant
      difference in the allelic frequency at 9065 C/T (chi(2) = 3.86, P = 0.049) in the
      stat6 gene. No differences were seen in genotype or allele frequencies of SNPs in
      the mu-opioid receptor gene or UGT2B7 gene. This study presents novel data
      suggesting that variation in genes involved in mu-opioid receptor signalling
      influence clinical response to morphine.

PMID- 16103898
TI  - Ab initio prediction of transcription factor targets using structural knowledge.
AB  - Current approaches for identification and detection of transcription factor
      binding sites rely on an extensive set of known target genes. Here we describe a
      novel structure-based approach applicable to transcription factors with no prior
      binding data. Our approach combines sequence data and structural information to
      infer context-specific amino acid-nucleotide recognition preferences. These are
      used to predict binding sites for novel transcription factors from the same
      structural family. We demonstrate our approach on the Cys(2)His(2) Zinc Finger
      protein family, and show that the learned DNA-recognition preferences are
      compatible with experimental results. We use these preferences to perform a
      genome-wide scan for direct targets of Drosophila melanogaster Cys(2)His(2)
      transcription factors. By analyzing the predicted targets along with gene
      annotation and expression data we infer the function and activity of these
      proteins.

PMID- 16103899
TI  - Extraction of transcript diversity from scientific literature.
AB  - Transcript diversity generated by alternative splicing and associated mechanisms
      contributes heavily to the functional complexity of biological systems. The
      numerous examples of the mechanisms and functional implications of these events
      are scattered throughout the scientific literature. Thus, it is crucial to have a
      tool that can automatically extract the relevant facts and collect them in a
      knowledge base that can aid the interpretation of data from high-throughput
      methods. We have developed and applied a composite text-mining method for
      extracting information on transcript diversity from the entire MEDLINE database
      in order to create a database of genes with alternative transcripts. It contains
      information on tissue specificity, number of isoforms, causative mechanisms,
      functional implications, and experimental methods used for detection. We have
      mined this resource to identify 959 instances of tissue-specific splicing. Our
      results in combination with those from EST-based methods suggest that alternative
      splicing is the preferred mechanism for generating transcript diversity in the
      nervous system. We provide new annotations for 1,860 genes with the potential for
      generating transcript diversity. We assign the MeSH term "alternative splicing"
      to 1,536 additional abstracts in the MEDLINE database and suggest new MeSH terms
      for other events. We have successfully extracted information about transcript
      diversity and semiautomatically generated a database, LSAT, that can provide a
      quantitative understanding of the mechanisms behind tissue-specific gene
      expression. LSAT (Literature Support for Alternative Transcripts) is publicly
      available at http://www.bork.embl.de/LSAT/.

PMID- 16103900
TI  - A phenomenological theory of spatially structured local synaptic connectivity.
AB  - The structure of local synaptic circuits is the key to understanding cortical
      function and how neuronal functional modules such as cortical columns are formed.
      The central problem in deciphering cortical microcircuits is the quantification
      of synaptic connectivity between neuron pairs. I present a theoretical model that
      accounts for the axon and dendrite morphologies of pre- and postsynaptic cells
      and provides the average number of synaptic contacts formed between them as a
      function of their relative locations in three-dimensional space. An important
      aspect of the current approach is the representation of a complex structure of an
      axonal/dendritic arbor as a superposition of basic structures-synaptic clouds.
      Each cloud has three structural parameters that can be directly estimated from
      two-dimensional drawings of the underlying arbor. Using empirical data available
      in literature, I applied this theory to three morphologically different types of
      cell pairs. I found that, within a wide range of cell separations, the theory is
      in very good agreement with empirical data on (i) axonal-dendritic contacts of
      pyramidal cells and (ii) somatic synapses formed by the axons of inhibitory
      interneurons. Since for many types of neurons plane arborization drawings are
      available from literature, this theory can provide a practical means for
      quantitatively deriving local synaptic circuits based on the actual observed
      densities of specific types of neurons and their morphologies. It can also have
      significant implications for computational models of cortical networks by making
      it possible to wire up simulated neural networks in a realistic fashion.

PMID- 16103901
TI  - The genomic pattern of tDNA operon expression in E. coli.
AB  - In fast-growing microorganisms, a tRNA concentration profile enriched in major
      isoacceptors selects for the biased usage of cognate codons. This optimizes
      translational rate for the least mass invested in the translational apparatus.
      Such translational streamlining is thought to be growth-regulated, but its
      genetic basis is poorly understood. First, we found in reanalysis of the E. coli
      tRNA profile that the degree to which it is translationally streamlined is nearly
      invariant with growth rate. Then, using least squares multiple regression, we
      partitioned tRNA isoacceptor pools to predicted tDNA operons from the E. coli K12
      genome. Co-expression of tDNAs in operons explains the tRNA profile significantly
      better than tDNA gene dosage alone. Also, operon expression increases
      significantly with proximity to the origin of replication, oriC, at all growth
      rates. Genome location explains about 15% of expression variation in a form, at a
      given growth rate, that is consistent with replication-dependent gene
      concentration effects. Yet the change in the tRNA profile with growth rate is
      less than would be expected from such effects. We estimated per-copy expression
      rates for all tDNA operons that were consistent with independent estimates for
      rDNA operons. We also found that tDNA operon location, and the location
      dependence of expression, were significantly different in the leading and lagging
      strands. The operonic organization and genomic location of tDNA operons are
      significant factors influencing their expression. Nonrandom patterns of location
      and strandedness shown by tDNA operons in E. coli suggest that their genomic
      architecture may be under selection to satisfy physiological demand for tRNA
      expression at high growth rates.

PMID- 16103902
TI  - microRNA target predictions across seven Drosophila species and comparison to
      mammalian targets.
AB  - microRNAs are small noncoding genes that regulate the protein production of genes
      by binding to partially complementary sites in the mRNAs of targeted genes. Here,
      using our algorithm PicTar, we exploit cross-species comparisons to predict, on
      average, 54 targeted genes per microRNA above noise in Drosophila melanogaster.
      Analysis of the functional annotation of target genes furthermore suggests
      specific biological functions for many microRNAs. We also predict combinatorial
      targets for clustered microRNAs and find that some clustered microRNAs are likely
      to coordinately regulate target genes. Furthermore, we compare microRNA
      regulation between insects and vertebrates. We find that the widespread extent of
      gene regulation by microRNAs is comparable between flies and mammals but that
      certain microRNAs may function in clade-specific modes of gene regulation. One of
      these microRNAs (miR-210) is predicted to contribute to the regulation of fly
      oogenesis. We also list specific regulatory relationships that appear to be
      conserved between flies and mammals. Our findings provide the most extensive
      microRNA target predictions in Drosophila to date, suggest specific functional
      roles for most microRNAs, indicate the existence of coordinate gene regulation
      executed by clustered microRNAs, and shed light on the evolution of microRNA
      function across large evolutionary distances. All predictions are freely
      accessible at our searchable Web site http://pictar.bio.nyu.edu.

PMID- 16103903
TI  - What makes ribosome-mediated transcriptional attenuation sensitive to amino acid
      limitation?
AB  - Ribosome-mediated transcriptional attenuation mechanisms are commonly used to
      control amino acid biosynthetic operons in bacteria. The mRNA leader of such an
      operon contains an open reading frame with "regulatory" codons, cognate to the
      amino acid that is synthesized by the enzymes encoded by the operon. When the
      amino acid is in short supply, translation of the regulatory codons is slow,
      which allows transcription to continue into the structural genes of the operon.
      When amino acid supply is in excess, translation of regulatory codons is rapid,
      which leads to termination of transcription. We use a discrete master equation
      approach to formulate a probabilistic model for the positioning of the RNA
      polymerase and the ribosome in the attenuator leader sequence. The model
      describes how the current rate of amino acid supply compared to the demand in
      protein synthesis (signal) determines the expression of the amino acid
      biosynthetic operon (response). The focus of our analysis is on the sensitivity
      of operon expression to a change in the amino acid supply. We show that
      attenuation of transcription can be hyper-sensitive for two main reasons. The
      first is that its response depends on the outcome of a race between two multi
      step mechanisms with synchronized starts: transcription of the leader of the
      operon, and translation of its regulatory codons. The relative change in the
      probability that transcription is aborted (attenuated) can therefore be much
      larger than the relative change in the time it takes for the ribosome to read a
      regulatory codon. The second is that the general usage frequencies of codons of
      the type used in attenuation control are small. A small percentage decrease in
      the rate of supply of the controlled amino acid can therefore lead to a much
      larger percentage decrease in the rate of reading a regulatory codon. We show
      that high sensitivity further requires a particular choice of regulatory codon
      among several synonymous codons for the same amino acid. We demonstrate the
      importance of a high fraction of regulatory codons in the control region.
      Finally, our integrated model explains how differences in leader sequence design
      of the trp and his operons of Escherichia coli and Salmonella typhimurium lead to
      high basal expression and low sensitivity in the former case, and to large
      dynamic range and high sensitivity in the latter. The model clarifies how
      mechanistic and systems biological aspects of the attenuation mechanism
      contribute to its overall sensitivity. It also explains structural differences
      between the leader sequences of the trp and his operons in terms of their
      different functions.

PMID- 16103904
TI  - Predicting functional gene links from phylogenetic-statistical analyses of whole
      genomes.
AB  - An important element of the developing field of proteomics is to understand
      protein-protein interactions and other functional links amongst genes. Across
      species correlation methods for detecting functional links work on the premise
      that functionally linked proteins will tend to show a common pattern of presence
      and absence across a range of genomes. We describe a maximum likelihood
      statistical model for predicting functional gene linkages. The method detects
      independent instances of the correlated gain or loss of pairs of proteins on
      phylogenetic trees, reducing the high rates of false positives observed in
      conventional across-species methods that do not explicitly incorporate a
      phylogeny. We show, in a dataset of 10,551 protein pairs, that the phylogenetic
      method improves by up to 35% on across-species analyses at identifying known
      functionally linked proteins. The method shows that protein pairs with at least
      two to three correlated events of gain or loss are almost certainly functionally
      linked. Contingent evolution, in which one gene's presence or absence depends
      upon the presence of another, can also be detected phylogenetically, and may
      identify genes whose functional significance depends upon its interaction with
      other genes. Incorporating phylogenetic information improves the prediction of
      functional linkages. The improvement derives from having a lower rate of false
      positives and from detecting trends that across-species analyses miss.
      Phylogenetic methods can easily be incorporated into the screening of large-scale
      bioinformatics datasets to identify sets of protein links and to characterise
      gene networks.

PMID- 16103905
TI  - PLoS Computational Biology: a new community journal.

PMID- 16103906
TI  - An open forum for computational biology.

PMID- 16103907
TI  - "Antedisciplinary" science.

PMID- 16103908
TI  - Susceptibility to superhelically driven DNA duplex destabilization: a highly
      conserved property of yeast replication origins.
AB  - Strand separation is obligatory for several DNA functions, including replication.
      However, local DNA properties such as A+T content or thermodynamic stability
      alone do not determine the susceptibility to this transition in vivo. Rather,
      superhelical stresses provide long-range coupling among the transition behaviors
      of all base pairs within a topologically constrained domain. We have developed
      methods to analyze superhelically induced duplex destabilization (SIDD) in
      genomic DNA that take into account both this long-range stress-induced coupling
      and sequence-dependent local thermodynamic stability. Here we apply this approach
      to examine the SIDD properties of 39 experimentally well-characterized
      autonomously replicating DNA sequences (ARS elements), which function as
      replication origins in the yeast Saccharomyces cerevisiae. We find that these ARS
      elements have a strikingly increased susceptibility to SIDD relative to their
      surrounding sequences. On average, these ARS elements require 4.78 kcal/mol less
      free energy to separate than do their immediately surrounding sequences, making
      them more than 2,000 times easier to open. Statistical analysis shows that the
      probability of this strong an association between SIDD sites and ARS elements
      arising by chance is approximately 4 x 10(-10). This local enhancement of the
      propensity to separate to single strands under superhelical stress has obvious
      implications for origin function. SIDD properties also could be used, in
      conjunction with other known origin attributes, to identify putative replication
      origins in yeast, and possibly in other metazoan genomes.

PMID- 16103909
TI  - Combinatorial pattern discovery approach for the folding trajectory analysis of a
      beta-hairpin.
AB  - The study of protein folding mechanisms continues to be one of the most
      challenging problems in computational biology. Currently, the protein folding
      mechanism is often characterized by calculating the free energy landscape versus
      various reaction coordinates, such as the fraction of native contacts, the radius
      of gyration, RMSD from the native structure, and so on. In this paper, we present
      a combinatorial pattern discovery approach toward understanding the global state
      changes during the folding process. This is a first step toward an unsupervised
      (and perhaps eventually automated) approach toward identification of global
      states. The approach is based on computing biclusters (or patterned clusters)
      each cluster is a combination of various reaction coordinates, and its signature
      pattern facilitates the computation of the Z-score for the cluster. For this
      discovery process, we present an algorithm of time complexity c in RO((N + nm)
      log n), where N is the size of the output patterns and (n x m) is the size of the
      input with n time frames and m reaction coordinates. To date, this is the best
      time complexity for this problem. We next apply this to a beta-hairpin folding
      trajectory and demonstrate that this approach extracts crucial information about
      protein folding intermediate states and mechanism. We make three observations
      about the approach: (1) The method recovers states previously obtained by
      visually analyzing free energy surfaces. (2) It also succeeds in extracting
      meaningful patterns and structures that had been overlooked in previous works,
      which provides a better understanding of the folding mechanism of the beta
      hairpin. These new patterns also interconnect various states in existing free
      energy surfaces versus different reaction coordinates. (3) The approach does not
      require calculating the free energy values, yet it offers an analysis comparable
      to, and sometimes better than, the methods that use free energy landscapes, thus
      validating the choice of reaction coordinates. (An abstract version of this work
      was presented at the 2005 Asia Pacific Bioinformatics Conference [1].).

PMID- 16103910
TI  - Improving the precision of the structure-function relationship by considering
      phylogenetic context.
AB  - Understanding the relationship between protein structure and function is one of
      the foremost challenges in post-genomic biology. Higher conservation of structure
      could, in principle, allow researchers to extend current limitations of
      annotation. However, despite significant research in the area, a precise and
      quantitative relationship between biochemical function and protein structure has
      been elusive. Attempts to draw an unambiguous link have often been complicated by
      pleiotropy, variable transcriptional control, and adaptations to genomic context,
      all of which adversely affect simple definitions of function. In this paper, I
      report that integrating genomic information can be used to clarify the link
      between protein structure and function. First, I present a novel measure of
      functional proximity between protein structures (F-score). Then, using F-score
      and other entirely automatic methods measuring structure and phylogenetic
      similarity, I present a three-dimensional landscape describing their inter
      relationship. The result is a "well-shaped" landscape that demonstrates the added
      value of considering genomic context in inferring function from structural
      homology. A generalization of methodology presented in this paper can be used to
      improve the precision of annotation of genes in current and newly sequenced
      genomes.

PMID- 16103911
TI  - A human-curated annotation of the Candida albicans genome.
AB  - Recent sequencing and assembly of the genome for the fungal pathogen Candida
      albicans used simple automated procedures for the identification of putative
      genes. We have reviewed the entire assembly, both by hand and with additional
      bioinformatic resources, to accurately map and describe 6,354 genes and to
      identify 246 genes whose original database entries contained sequencing errors
      (or possibly mutations) that affect their reading frame. Comparison with other
      fungal genomes permitted the identification of numerous fungus-specific genes
      that might be targeted for antifungal therapy. We also observed that, compared to
      other fungi, the protein-coding sequences in the C. albicans genome are
      especially rich in short sequence repeats. Finally, our improved annotation
      permitted a detailed analysis of several multigene families, and comparative
      genomic studies showed that C. albicans has a far greater catabolic range,
      encoding respiratory Complex 1, several novel oxidoreductases and ketone body
      degrading enzymes, malonyl-CoA and enoyl-CoA carriers, several novel amino acid
      degrading enzymes, a variety of secreted catabolic lipases and proteases, and
      numerous transporters to assimilate the resulting nutrients. The results of these
      efforts will ensure that the Candida research community has uniform and
      comprehensive genomic information for medical research as well as for future
      diagnostic and therapeutic applications.

PMID- 16103913
TI  - The whole side of it--an interview with Neil Risch. Interview by Jane Gitschier.

PMID- 16103912
TI  - Fog2 is required for normal diaphragm and lung development in mice and humans.
AB  - Congenital diaphragmatic hernia and other congenital diaphragmatic defects are
      associated with significant mortality and morbidity in neonates; however, the
      molecular basis of these developmental anomalies is unknown. In an analysis of
      E18.5 embryos derived from mice treated with N-ethyl-N-nitrosourea, we identified
      a mutation that causes pulmonary hypoplasia and abnormal diaphragmatic
      development. Fog2 (Zfpm2) maps within the recombinant interval carrying the N
      ethyl-N-nitrosourea-induced mutation, and DNA sequencing of Fog2 identified a
      mutation in a splice donor site that generates an abnormal transcript encoding a
      truncated protein. Human autopsy cases with diaphragmatic defect and pulmonary
      hypoplasia were evaluated for mutations in FOG2. Sequence analysis revealed a de
      novo mutation resulting in a premature stop codon in a child who died on the
      first day of life secondary to severe bilateral pulmonary hypoplasia and an
      abnormally muscularized diaphragm. Using a phenotype-driven approach, we have
      established that Fog2 is required for normal diaphragm and lung development, a
      role that has not been previously appreciated. FOG2 is the first gene implicated
      in the pathogenesis of nonsyndromic human congenital diaphragmatic defects, and
      its necessity for pulmonary development validates the hypothesis that neonates
      with congenital diaphragmatic hernia may also have primary pulmonary
      developmental abnormalities.

PMID- 16103914
TI  - New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a
      Caenorhabditis elegans genomic RNAi screen.
AB  - Most of our knowledge about the regulation of aging comes from mutants originally
      isolated for other phenotypes. To ask whether our current view of aging has been
      affected by selection bias, and to deepen our understanding of known longevity
      pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones
      that extend lifespan. We identified 23 new longevity genes affecting signal
      transduction, the stress response, gene expression, and metabolism and assigned
      these genes to specific longevity pathways. Our most important findings are (i)
      that dietary restriction extends C. elegans' lifespan by down-regulating
      expression of key genes, including a gene required for methylation of many
      macromolecules, (ii) that integrin signaling is likely to play a general,
      evolutionarily conserved role in lifespan regulation, and (iii) that specific
      lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion.
      Surprisingly, of the new genes that have conserved sequence domains, only one
      could not be associated with a known longevity pathway. Thus, our current view of
      the genetics of aging has probably not been distorted substantially by selection
      bias.

PMID- 16103915
TI  - Using microarrays to facilitate positional cloning: identification of tomosyn as
      an inhibitor of neurosecretion.
AB  - Forward genetic screens have been used as a powerful strategy to dissect complex
      biological pathways in many model systems. A significant limitation of this
      approach has been the time-consuming and costly process of positional cloning and
      molecular characterization of the mutations isolated in these screens. Here, the
      authors describe a strategy using microarray hybridizations to facilitate
      positional cloning. This method relies on the fact that premature stop codons
      (i.e., nonsense mutations) constitute a frequent class of mutations isolated in
      screens and that nonsense mutant messenger RNAs are efficiently degraded by the
      conserved nonsense-mediated decay pathway. They validate this strategy by
      identifying two previously uncharacterized mutations: (1) tom-1, a mutation found
      in a forward genetic screen for enhanced acetylcholine secretion in
      Caenorhabditis elegans, and (2) an apparently spontaneous mutation in the hif-1
      transcription factor gene. They further demonstrate the broad applicability of
      this strategy using other known mutants in C. elegans,Arabidopsis, and mouse.
      Characterization of tom-1 mutants suggests that TOM-1, the C. elegans ortholog of
      mammalian tomosyn, functions as an endogenous inhibitor of neurotransmitter
      secretion. These results also suggest that microarray hybridizations have the
      potential to significantly reduce the time and effort required for positional
      cloning.

PMID- 16103917
TI  - Pseudogenization of a sweet-receptor gene accounts for cats' indifference toward
      sugar.
AB  - Although domestic cats (Felis silvestris catus) possess an otherwise functional
      sense of taste, they, unlike most mammals, do not prefer and may be unable to
      detect the sweetness of sugars. One possible explanation for this behavior is
      that cats lack the sensory system to taste sugars and therefore are indifferent
      to them. Drawing on work in mice, demonstrating that alleles of sweet-receptor
      genes predict low sugar intake, we examined the possibility that genes involved
      in the initial transduction of sweet perception might account for the
      indifference to sweet-tasting foods by cats. We characterized the sweet-receptor
      genes of domestic cats as well as those of other members of the Felidae family of
      obligate carnivores, tiger and cheetah. Because the mammalian sweet-taste
      receptor is formed by the dimerization of two proteins (T1R2 and T1R3; gene
      symbols Tas1r2 and Tas1r3), we identified and sequenced both genes in the cat by
      screening a feline genomic BAC library and by performing PCR with degenerate
      primers on cat genomic DNA. Gene expression was assessed by RT-PCR of taste
      tissue, in situ hybridization, and immunohistochemistry. The cat Tas1r3 gene
      shows high sequence similarity with functional Tas1r3 genes of other species.
      Message from Tas1r3 was detected by RT-PCR of taste tissue. In situ hybridization
      and immunohistochemical studies demonstrate that Tas1r3 is expressed, as
      expected, in taste buds. However, the cat Tas1r2 gene shows a 247-base pair
      microdeletion in exon 3 and stop codons in exons 4 and 6. There was no evidence
      of detectable mRNA from cat Tas1r2 by RT-PCR or in situ hybridization, and no
      evidence of protein expression by immunohistochemistry. Tas1r2 in tiger and
      cheetah and in six healthy adult domestic cats all show the similar deletion and
      stop codons. We conclude that cat Tas1r3 is an apparently functional and
      expressed receptor but that cat Tas1r2 is an unexpressed pseudogene. A functional
      sweet-taste receptor heteromer cannot form, and thus the cat lacks the receptor
      likely necessary for detection of sweet stimuli. This molecular change was very
      likely an important event in the evolution of the cat's carnivorous behavior.

PMID- 16103918
TI  - Susceptibility to neurodegeneration in a glaucoma is modified by Bax gene dosage.
AB  - In glaucoma, harmful intraocular pressure often contributes to retinal ganglion
      cell death. It is not clear, however, if intraocular pressure directly insults
      the retinal ganglion cell axon, the soma, or both. The pathways that mediate
      pressure-induced retinal ganglion cell death are poorly defined, and no molecules
      are known to be required. DBA/2J mice deficient in the proapoptotic molecule BCL2
      associated X protein (BAX) were used to investigate the roles of BAX-mediated
      cell death pathways in glaucoma. Both Bax+/- and Bax-/- mice were protected from
      retinal ganglion cell death. In contrast, axonal degeneration was not prevented
      in either Bax+/- or Bax-/- mice. While BAX deficiency did not prevent axonal
      degeneration, it did slow axonal loss. Additionally, we compared the effects of
      BAX deficiency on the glaucoma to its effects on retinal ganglion cell death due
      to two insults that are proposed to participate in glaucoma. As in the glaucoma,
      BAX deficiency protected retinal ganglion cells after axon injury by optic nerve
      crush. However, it did not protect retinal ganglion cells from N-methyl-D
      aspartate (NMDA)-induced excitotoxicity. BAX is required for retinal ganglion
      cell death in an inherited glaucoma; however, it is not required for retinal
      ganglion cell axon degeneration. This indicates that distinct somal and axonal
      degeneration pathways are active in this glaucoma. Finally, our data support a
      role for optic nerve injury but not for NMDA receptor-mediated excitotoxicity in
      this glaucoma. These findings indicate a need to understand axon-specific
      degeneration pathways in glaucoma, and they suggest that distinct somal and
      axonal degeneration pathways may need to be targeted to save vision.

PMID- 16103919
TI  - Evidence for domesticated and wild populations of Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae is predominantly found in association with human
      activities, particularly the production of alcoholic beverages. S. paradoxus, the
      closest known relative of S. cerevisiae, is commonly found on exudates and bark
      of deciduous trees and in associated soils. This has lead to the idea that S.
      cerevisiae is a domesticated species, specialized for the fermentation of
      alcoholic beverages, and isolates of S. cerevisiae from other sources simply
      represent migrants from these fermentations. We have surveyed DNA sequence
      diversity at five loci in 81 strains of S. cerevisiae that were isolated from a
      variety of human and natural fermentations as well as sources unrelated to
      alcoholic beverage production, such as tree exudates and immunocompromised
      patients. Diversity within vineyard strains and within sake strains is low,
      consistent with their status as domesticated stocks. The oldest lineages and the
      majority of variation are found in strains from sources unrelated to wine
      production. We propose a model whereby two specialized breeds of S. cerevisiae
      have been created, one for the production of grape wine and one for the
      production of sake wine. We estimate that these two breeds have remained isolated
      from one another for thousands of years, consistent with the earliest
      archeological evidence for wine-making. We conclude that although there are
      clearly strains of S. cerevisiae specialized for the production of alcoholic
      beverages, these have been derived from natural populations unassociated with
      alcoholic beverage production, rather than the opposite.

PMID- 16103920
TI  - Diversity of flowering responses in wild Arabidopsis thaliana strains.
AB  - Although multiple environmental cues regulate the transition to flowering in
      Arabidopsis thaliana, previous studies have suggested that wild A. thaliana
      accessions fall primarily into two classes, distinguished by their requirement
      for vernalization (extended winter-like temperatures), which enables rapid
      flowering under long days. Much of the difference in vernalization response is
      apparently due to variation at two epistatically acting loci, FRI and FLC. We
      present the response of over 150 wild accessions to three different environmental
      variables. In long days, FLC is among those genes whose expression is most highly
      correlated with flowering. In short days, FRI and FLC are less important,
      although their contribution is still significant. In addition, there is
      considerable variation not only in vernalization response, but also in the
      response to differences in day length or ambient growth temperature. The
      identification of accessions that flower relatively early or late in specific
      environments suggests that many of the flowering-time pathways identified by
      mutagenesis, such as those that respond to day length, contribute to flowering
      time variation in the wild. In contrast to differences in vernalization
      requirement, which are mainly mediated by FRI and FLC, it seems that variation in
      these other pathways is due to allelic effects at several different loci.

PMID- 16103921
TI  - Cell-autonomous death of cerebellar purkinje neurons with autophagy in Niemann
      Pick type C disease.
AB  - Niemann-Pick type C is a neurodegenerative lysosomal storage disorder caused by
      mutations in either of two genes, npc1 and npc2. Cells lacking Npc1, which is a
      transmembrane protein related to the Hedgehog receptor Patched, or Npc2, which is
      a secreted cholesterol-binding protein, have aberrant organelle trafficking and
      accumulate large quantities of cholesterol and other lipids. Though the Npc
      proteins are produced by all cells, cerebellar Purkinje neurons are especially
      sensitive to loss of Npc function. Since Niemann-Pick type C disease involves
      circulating molecules such as sterols and steroids and a robust inflammatory
      response within the brain parenchyma, it is crucial to determine whether external
      factors affect the survival of Purkinje cells (PCs). We investigated the basis of
      neurodegeneration in chimeric mice that have functional npc1 in only some cells.
      Death of mutant npc1 cells was not prevented by neighboring wild-type cells, and
      wild-type PCs were not poisoned by surrounding mutant npc1 cells. PCs undergoing
      cell-autonomous degeneration have features consistent with autophagic cell death.
      Chimeric mice exhibited a remarkable delay and reduction of wasting and ataxia
      despite their substantial amount of mutant tissue and dying cells, revealing a
      robust mechanism that partially compensates for massive PC death.

PMID- 16103922
TI  - A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in
      pheochromocytomas.
AB  - Pheochromocytomas are neural crest-derived tumors that arise from inherited or
      sporadic mutations in at least six independent genes. The proteins encoded by
      these multiple genes regulate distinct functions. We show here a functional link
      between tumors with VHL mutations and those with disruption of the genes encoding
      for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription
      profile of reduced oxidoreductase is detected in all three of these tumor types,
      together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The
      oxidoreductase defect, not previously detected in VHL-null tumors, is explained
      by suppression of the SDHB protein, a component of mitochondrial complex II. The
      decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function
      and loss-of-function analyses show that the link between hypoxia signals (via
      VHL) and mitochondrial signals (via SDH) is mediated by HIF1alpha. These findings
      explain the shared features of pheochromocytomas with VHL and SDH mutations and
      suggest an additional mechanism for increased HIF1alpha activity in tumors.

PMID- 16103924
TI  - Targets, targets everywhere--so where are the new antibacterial drugs?

PMID- 16103923
TI  - Positive selection drives the evolution of rhino, a member of the heterochromatin
      protein 1 family in Drosophila.
AB  - Heterochromatin comprises a significant component of many eukaryotic genomes. In
      comparison to euchromatin, heterochromatin is gene poor, transposon rich, and
      late replicating. It serves many important biological roles, from gene silencing
      to accurate chromosome segregation, yet little is known about the evolutionary
      constraints that shape heterochromatin. A complementary approach to the
      traditional one of directly studying heterochromatic DNA sequence is to study the
      evolution of proteins that bind and define heterochromatin. One of the best
      markers for heterochromatin is the heterochromatin protein 1 (HP1), which is an
      essential, nonhistone chromosomal protein. Here we investigate the molecular
      evolution of five HP1 paralogs present in Drosophila melanogaster. Three of these
      paralogs have ubiquitous expression patterns in adult Drosophila tissues, whereas
      HP1D/rhino and HP1E are expressed predominantly in ovaries and testes
      respectively. The HP1 paralogs also have distinct localization preferences in
      Drosophila cells. Thus, Rhino localizes to the heterochromatic compartment in
      Drosophila tissue culture cells, but in a pattern distinct from HP1A and lysine-9
      dimethylated H3. Using molecular evolution and population genetic analyses, we
      find that rhino has been subject to positive selection in all three domains of
      the protein: the N-terminal chromo domain, the C-terminal chromo-shadow domain,
      and the hinge region that connects these two modules. Maximum likelihood analysis
      of rhino sequences from 20 species of Drosophila reveals that a small number of
      residues of the chromo and shadow domains have been subject to repeated positive
      selection. The rapid and positive selection of rhino is highly unusual for a gene
      encoding a chromosomal protein and suggests that rhino is involved in a genetic
      conflict that affects the germline, belying the notion that heterochromatin is
      simply a passive recipient of "junk DNA" in eukaryotic genomes.

PMID- 16103925
TI  - European Society of Gene Therapy (ESGT) Seventh Meeting. 26-28 November 1999,
      Munich, Germany.
AB  - This meeting gave an excellent overview of the recent developments in gene
      therapy. Much research effort has focused on the improvement and de novo
      construction of gene vectors, on characterizing their mechanisms of action and on
      their interactions with, and in, living organisms. The continual improvements in
      understanding disease at a molecular level and the progress in cell biology,
      immunology and related fields have opened the way for novel gene therapy
      approaches. The gene therapeutic strategy has proven to be feasible and efficient
      in numerous preclinical (animal) models of a variety of diseases. On the other
      hand, applying this experience to humans has turned out to be difficult.
      Currently, the field is rapidly moving into clinical applications. No major
      limiting side effects have been observed in patients in the phase I and later
      stage trials presented. Nonetheless, years of preclinical and clinical research
      will be required before gene therapy can be considered a reliable and efficient
      therapeutic approach with broad applicability.

PMID- 16103926
TI  - Gene-targeted therapeutic strategies--Royal Pharmaceutical Society Symposium. 9
      10 December 1999, London, UK.
AB  - This meeting highlighted the approaches that are currently available for gene
      targeted therapeutics. The meeting focused on two strategies: antigene and anti
      message. Polyamides (an example of antigene targeting) have exhibited significant
      antiviral activity, particularly against AIDS. The design of these agents and the
      mechanisms by which these compounds interact with DNA were discussed. Antisense
      oligonucleotides and ribozymes, agents used in the anti-message strategies, are
      proving to be attractive drug candidates for cancer chemotherapy. Antisense
      technology has been used for patients with B-cell lymphomas, resulting in
      complete remission of the disease in some cases. The unavailability of
      appropriate delivery systems for these DNA-targeting drugs continues to limit
      their widespread use. As was emphasized in this meeting, DNA-targeting drugs will
      continue to play an important role in clinical medicine for the foreseeable
      future.

PMID- 16103927
TI  - Antibody engineering--IBC's Tenth International Conference. 6-9 December 1999, La
      Jolla, CA, USA.
AB  - This meeting covered emergent antibody technologies through preclinical and
      clinical development of antibodies to the latest clinical data with antibody
      drugs. On the technology front, human antibody phage libraries have increased in
      size and quality, and have been combined with high-throughput screening methods.
      Such phage libraries have become powerful tools for the generation of antibody
      therapeutics and may also prove useful in the identification of new therapeutic
      targets. Indeed, four high affinity human antibodies from phage libraries are
      currently in clinical trials. Transgenic mice containing human immunoglobulin
      genes have also emerged as a route to high affinity human antibodies, including
      two that have progressed into the clinic. Molecular evolution of scFv fragments
      to increase their stability has led to improved localization to tumors in animal
      models and to their enhanced performance as intrabodies. In clinical trials,
      significant efficacy with minimal or acceptable toxicities were reported for the
      chimeric Fab fragment, ReoPro (abciximab; Centocor Inc), in coronary artery
      disease; the humanized anti-HER2 antibody, Herceptin (trastuzumab; Genentech
      Inc), in metastatic breast cancer; and, the humanized anti-IgE antibody, E25
      (Genentech Inc), in asthma and allergic rhinitis.

PMID- 16103928
TI  - Design, production and evaluation of novel diagnostic and therapeutic reagents. 6
      9 December 1999, La Jolla, CA, USA.
AB  - The timing of this meeting was indeed auspicious; the antibody engineers were
      able to celebrate the end of the decade and millennium with the launch of several
      dominant biotechnology products. Currently, over 30% of all new protein-based
      therapeutic products before the FDA are based on antibody designs. In the last 12
      months, antibodies have hit the international headlines (almost weekly) due to
      FDA approvals and massive expansion in commercial sales of antithrombotic,
      anticancer and antiviral antibodies. The latest examples include IDEC
      Pharmaceuticals Corp's rituximab (Rituxan) and Coulter Pharmaceutical Inc's
      Bexxar (I-131 tositumomab), both targeting CD20 for therapy of non-Hodgkin's
      lymphoma, and also Herceptin (trastuzumab; Genentech Inc) for breast cancer.
      Sales of these antibodies for cancer therapy are potentially over dollars 1
      billion in 2001 and have revitalized the interest of the biotechnology industry.
      Indeed, 'antibodies' are once-again a buzz-word.

PMID- 16103929
TI  - American College of Rheumatology--63rd Annual Meeting. 13-17 November 1999,
      Boston, MA, USA.

PMID- 16103930
TI  - Post-ASH Second Annual Meeting. 21 December 1999, Grimbergen, Belgium.

PMID- 16103931
TI  - American College of Neuropsychopharmacology--annual meeting. 12-16 December 1999,
      Acapulco, Mexico.

PMID- 16103933
TI  - Chemotherapy Foundation: Innovative Cancer Therapy for Tomorrow--XVII Symposium.
      3-6 November 1999, Mount Sinai School of Medicine, New York, NY, USA.

PMID- 16103932
TI  - Drug Delivery Systems--Fifth US-Japan Symposium. 12-17 December 1999, Lahaina,
      Hawaii.
AB  - The field of drug delivery is moving rapidly from the more efficacious delivery
      of 'old' drugs, to the delivery of therapeutic peptides, proteins,
      oligonucleotides and genes. Liposomes, polymers, microbubbles, nanoparticles,
      wafers and chips are the jargon, and entrepreneurialism is the prevailing force.
      Indeed, the scientific spirit is overwhelmed by the push to market, as fledgling
      companies compete or collaborate with the established pharma industry in
      converting concepts into profits. The 'Holy Grail' is a slice of the multi
      billion dollar global market for these specialized, high-tech products.

PMID- 16103934
TI  - Osteoporosis therapies--future leads and current clinical trials. 13-14 December
      1999, London, UK.
AB  - This IBC conference focused on research areas most likely to generate novel leads
      for future osteoporosis therapies. There was particular emphasis placed on
      inhibitors of bone resorption, including progress in the development of existing
      compounds, such as raloxifene (Evista; Eli Lilly & Co) and the nitrogen
      containing bisphosphonates, as well as insights into novel agents, such as the
      integrin receptors. It was also generally accepted that the next generation of
      osteoporosis therapies would target osteoblasts with a view to stimulating bone
      formation. Potential for developing such novel therapies using genomic approaches
      was also presented.

PMID- 16103935
TI  - Angiogenesis: Therapeutic Applications--Second Annual Meeting. 13-14 December
      1999, Washington DC, USA.

PMID- 16103936
TI  - Breast cancer--22nd annual symposium. 8-11 December 1999, San Antonio, TX, USA.
AB  - This symposium focused on trials conducted primarily on patients with metastatic
      breast cancer with the aim of defining the safest and most effective treatment
      regimens. The combination of paclitaxel and doxorubicin procured a survival
      advantage, though confirmation of this multicenter randomized data is awaited
      from other studies. In elucidating the most effective agents to use with
      trastuzumab (Herceptin; Genentech Inc), results with vinorelbine (Navelbine;
      Pierre Fabre SA) were most encouraging. Randomized studies of hormonal agents in
      the adjuvant setting have demonstrated an improved relapse-free survival with
      goserelin (Zoladex) and anastrozole (Arimidex; both AstraZeneca plc), compared to
      tamoxifen. Data were presented suggesting tamoxifen leads to a worse outcome when
      prescribed to pre-menopausal estrogen-receptor negative patients. The use of
      newer selective estrogen receptor modulators (SERMs) was discussed with
      particular reference to LY-353381 (Eli Lilly and Co) and fulvestrant (AstraZeneca
      plc), both of which appear to have impressive profiles of action when compared to
      tamoxifen.

PMID- 16103937
TI  - Predictive toxicology in drug discovery--second international conference. 10-11
      November, 1999, New Orleans, LA, USA.

PMID- 16103938
TI  - Combinatorial Chemistry '99--IIR's Second Annual Conference and Exhibition Forum.
      6-7 December 1999, London, UK.

PMID- 16103939
TI  - Frontiers in pharmacology and therapeutics in the 21st century--International
      Congress. 1-4 December, 1999, New Delhi, India.

PMID- 16103940
TI  - Angiotensin II receptor antagonists: where do we stand?
AB  - Losartan, the first angiotensin II receptor antagonist was introduced in 1994.
      Since then, five other antagonists have been launched for the management of
      hypertension. In recent years, numerous studies have demonstrated that
      angiotensin II antagonists are as effective as other antihypertensive agents but
      with a better tolerability profile. The challenge with these agents is now to
      demonstrate their potential benefits on morbidity and mortality, and several very
      large clinical trials are therefore running in hypertension, congestive heart
      failure and diabetic nephropathy. In addition, research is focusing intensively
      on defining the role of angiotensin AT2 receptors, and the potential benefits of
      combining ACE inhibitors and angiotensin II antagonists.

PMID- 16103941
TI  - Recent developments in the chemotherapy of malaria.
AB  - Malaria remains a major infectious disease and is worsening in some areas, partly
      because of the spread of resistance to established antimalarial drugs. New drugs
      are urgently needed to combat the protozoan parasite, Plasmodium. This review
      covers new developments, including artemisinin derivatives, synthetic peroxides,
      folate pathway inhibitors, primaquine analogs and proteinase inhibitors. However,
      few of these agents are in clinical trials and many are derived from chemical
      classes already used extensively against malaria. The emerging understanding of
      parasite biology and new technological developments in drug discovery offer hope
      of improvement, but this will require increased interest from the pharmaceutical
      industry.

PMID- 16103942
TI  - Glycine antagonists for the treatment of stroke: a literature survey (1997-1999).

PMID- 16103943
TI  - Atiprimod (AnorMED).
AB  - Atiprimod is a macrophage-targeting oral cytokine inhibitor which is being
      developed by AnorMED as a potential treatment for rheumatoid arthritis and other
      autoimmune diseases. Phase I trials have been successfully completed and phase II
      multicenter trials have been approved by the FDA [303260]. The compound was
      discovered in a joint research and development program with SmithKline and French
      (now SmithKline Beecham, SB) but following acceptance of the phase II protocol by
      the FDA, SB decided not to proceed with further development of atiprimod as a
      result of an internal restructuring program [350042]. All rights to atiprimod and
      other azaspiranes developed in this program have reverted to AnorMED, which is
      seeking corporate partners for further development of the compound
      [303260,337657]. The compound was originally disclosed in European patent, EP
      00310321, entitled 'Preparation of N-aminoalkyl-2-azaspiro[4.5]decanes and
      analogs as immunosuppresants', while a cost-effective, efficacious pilot plant
      synthesis has also been described [298722].

PMID- 16103944
TI  - AG-3340 (Agouron Pharmaceuticals Inc).
AB  - Agouron Pharmaceuticals is developing AG-3340 (prinomastat), the lead compound in
      a series of structurally related metalloproteinase inhibitors, for the potential
      treatment of cancer and age-related macular degeneration. AG-3340, an oral, non
      peptide inhibitor of gelatinase types A and B (MMP-2 and -9), MT1-MP (MMP-14) and
      collagenase III [234058], was selected following demonstration of activity in a
      variety of in vivo preclinical models upon oral dosing. In May 1999, phase III
      trials for lung and prostate cancers of AG-3340 in front-line combination with
      chemotherapy was begun in the US and Canada [286380,326640]. The tested dose for
      these trials is 5 to 15 mg bid. Following demonstration of the enhanced efficacy
      of chemotherapy when supplemented with AG-3340 in preclinical tumor models, pilot
      combination studies and double-blinded, placebo-controlled phase III trials in
      700 patients are in progress for the treatment of non-small cell lung cancer or
      advanced hormone-refractory prostate cancer [302584,327014]. In August 1999,
      Agouron initiated a second, confirmatory phase III trial of AG-3340 in
      combination with chemotherapy in patients with advanced non-small cell lung
      cancer [337253]. Pharmacokinetic studies have been conducted in healthy male
      volunteers and single agent dose-escalation studies in patients demonstrated
      toxicities (grade 1 or 2; joint related) were not doselimiting [302238]. At the
      10th European Organization for Research and Treatment of Cancer (EORTC) meeting
      in Amsterdam (June 1998), Agouron released encouraging results from two phase I
      studies and one preclinical study of AG-3340 [289688]. In a further 15- patient,
      phase I study of AG-3340 with paclitaxel and carboplatin, the combination was
      safe and well tolerated [326268]. AG-3340 has demonstrated significant
      antimetastatic and antitumor activity in animal models, as well as oral
      bioavailability and a favorable pharmacokinetic profile. Daily doses of 50 mg/kg
      completely halted growth of Lewis lung carcinomas in two thirds of test animals
      and reduced the formation of lung metastasis (0.5 mm in diameter) by 90%
      [205708]. In December 1997, Roche announced it would discontinue its cancer R&D
      collaborations with Agouron on AG-3340 as it did not fulfill its scientific and
      business objectives [271723]. Agouron is investigating analogs of AG-3340 which
      are undergoing animal studies [332841].

PMID- 16103945
TI  - Stem cell therapy (Aastrom Biosciences Inc).
AB  - The expansion of human stem cells and their genetic manipulation represent areas
      of increasing interest in the field of stem cell transplantation. Previously,
      stem cell transplantation has been accomplished by using cellular products
      obtained by large volume bone marrow or peripheral blood harvest. Difficulties
      with this approach include inadequate cell numbers and tumor cell contamination.
      Furthermore, for gene transfer modalities requiring proliferating progenitor
      cells, low gene expression would be expected in these products. To address these
      difficulties, the AastromReplicell System has been developed as a fully closed
      and automated system for expanding hematopoietic cells. Investigators at Aastrom
      have evaluated the conditions needed for optimal growth including the need for
      unpurified bone marrow or cord blood mononuclear cells, high cell densities,
      serum-containing medium and certain types of plastic surfaces. Studies have now
      been initiated to demonstrate the feasibility of generating enough cells to fully
      reconstitute hematopoiesis from small volumes of cellular progenitors. It has
      also been demonstrated that tumor cell contamination passively decreases during
      the culture period. It now remains to be shown in a direct comparison that this
      approach yields greater efficacy and a lower cost than transplantation with
      unmanipulated large volume marrow or peripheral blood stem cell products.

PMID- 16103946
TI  - [Posttraumatic palsy of the radial nerve -- diagnosis and surgical management].

PMID- 16103950
TI  - [The anatomy of the surgical treatment of migraine].
AB  - OBJECTIVE: The transpalpebral resection of the corrugator and depressor
      supercilii muscles is a new treatment option for migraine headaches. Hyperactive
      contractility of these muscles can provoke the peripheral compression of the
      supratrochlear nerve and induce a neurogenic inflammation triggering the symptoms
      of migraine. In order to gather detailed knowledge of the respective anatomy in
      the eyebrow region, a macroscopic cadaver study was conducted. MATERIALS AND
      METHODS: The relevant muscles of the forehead, glabella and eyebrow were
      dissected in five fresh, non-preserved heads. The supracanthal origins and dermal
      points of insertion were marked. Following the preparation of the neurovascular
      structures, the muscles were measured and weighed. The course of the supraorbital
      and supratrochlear nerves was demonstrated from the forehead to the orbital
      cavity. RESULTS: There are three, paired groups of muscles in the superomedial
      region of the orbital rim. They can be divided into the superficial frontalis and
      procerus muscle, the orbicularis muscle in a middle layer and the corrugator and
      depressor supercilii in a deeper layer. The corrugator measured approximately 4.5
      cm, whose origin is superior and posterior to the depressor origin situated
      cranial to the medial canthus. The corrugator inserts lateral to the exit of the
      supraorbital nerve in the dermis above the eyebrow after penetrating the
      orbicularis and frontalis muscles and a subgaleal fat pad. The length and weight
      of the muscles is highly variable. The muscle is penetrated by the supratrochlear
      nerve whereas the supraorbital nerve runs underneath it. The corrugator is
      innervated medially and laterally by branches of the facial nerve. CONCLUSION: A
      detailed knowledge of the complex arrangement of the muscles acting upon the
      glabella and the different communicating subgaleal and preseptal fat pads allow
      the identification and resection of the corrugator and depressor muscles without
      damaging the supratrochlear nerve. The course of the specific nerves is variable.
      The double-innervation of the corrugator suggests its complete resection instead
      of the selective denervation of the muscle.

PMID- 16103951
TI  - [The modified Brooker classification for evaluation of heterotopic ossifications
      in total hip replacement].
AB  - INTRODUCTION: To evaluate heterotopic ossifications (HTO) in total hip
      replacement several classifications have been developed. Most often the
      classifications according to Brooker or Arcq are used. These systems enable the
      description of HTO on x-rays in ap view, functional aspects like range of motion
      are not evaluated. In several studies we could observe that patients with HTO IV
      degrees according to Brooker ("ankylosis") had a free or excellent range of
      motion. We introduce a modified Brooker classification system which enables the
      evaluation of HTO in two X-ray planes and allows in addition a description of hip
      function. PATIENTS AND METHOD: On the a.-p. X-ray view the original Brooker
      classification is used, on the lateral view the Brooker classification ventrally
      and dorsally of the longitudinal axis of the stem of the total hip replacement is
      used. In addition functional deficits as a sequalae of HTO are documented (1:
      yes; 2: no). The new classification system is used in 10 cases with HTO IV
      degrees according to Brooker in the a.-p .view. RESULTS: 8 cases with "ankylosis"
      according to Brooker showed a good range of motion. In these cases HTO I-III
      degrees according to Brooker were found in the lateral view. In the ap view these
      HTO were evaluated as HTO IV degrees because of an overlapping effect.
      DISCUSSION: The new classification using X-rays in two planes allows to describe
      HTO sufficiently especially in respect to hip function. The most important
      advantage of this new classification is the fact that it modifies only a widly
      used and accepted system. This may lead to a high acceptance of the new
      classification.

PMID- 16103952
TI  - [Material removal after anterio-posterior spondylodesis -- necessity of posterior
      instrumentation removal after osseous fusion].
AB  - BACKGROUND: The present study on spondylitis patients with anterio-posterior
      spondylodesis was carried out to get a recommendation whether material removal is
      necessary after osseous fusion. METHODS: A total of 12 patients with spondylitis
      were operated on at the Orthopaedic Department of Ludwig-Maximilians-University
      Munich with posterior instrumentation after debridement and fusion with
      autologous bone transplant. In a prospective clinical investigation we examined
      our patients regarding clinical and radiological outcome preoperatively, 2 weeks,
      12 months and 4.9 years after operation. We paid special attention on
      complications and loss of correction in leaving posterior instrumentation.
      RESULTS: Compared with the advanced clinical signs of spondylitis, minor intra-
      and postoperative complications were seen. Two patients showed superficial wound
      infections with fistulization because of the posterior implants 3 years
      postoperatively. Both cases closed after revision and material removal without
      complications. 12 months and 4.9 years postoperatively the average loss of
      correction was constant 2 degrees . CONCLUSION: Generally material removal of
      posterior spinal instruments results in a significant loss of correction in the
      spondylodesis segment. Our study shows, that persisting posterior instrumentation
      could prevent loss of correction. On the other hand we recommend material removal
      in case of spondylodesis after osseous fusion to prevent wound healing
      complications.

PMID- 16103953
TI  - [A comparative study of unstable per- and intertrochanteric femoral fractures
      treated with dynamic hip screw (DHS) and trochanteric butt-press plate vs.
      proximal femoral nail (PFN)].
AB  - The aim of the present paper is to compare the results obtained using two
      osteosynthesis systems developed for the surgical treatment of unstable fractures
      of the trochanteric region of the femur: the proximal femoral nail (PFN) and the
      dynamic hip screw (DHS) with trochanteric butt-press plate (TBPP). From December
      1997 to November 2000, 173 patients with instable trochanteric fractures (type 31
      A-2 and A-3 according to the AO-classification) had osteosynthesis by PFN (n =
      122) or DHS/TBPP (n = 51). The average patient age was 74 years (range 27 to 98).
      No significant differences between the two study groups were observed with regard
      to age, sex, and rate of fracture types. At an average follow-up of 17 months the
      radiological and clinical outcome according to the score of "Merle d'Aubigne" was
      analysed in 61 % of all patients. All fractures were healed with no difference in
      functional outcome between the two groups. In the case of PFN 17.2 % revisions
      were necessary and in the case of DHS with TBPP 21.6 %. A shorter operation time
      (43 vs. 61 min) and a considerable shorter in-patient stay (20 vs. 24 days) were
      common with PFN. Full-weight-bearing immediately after the osteosynthesis was
      possible for 98 % of the PFN patients and 81 % of the DHS/TBPP patients. The
      DHS/TBPP osteosynthesis in instable trochanteric fractures is associated with a
      higher incidence of complications. Therefore we recommend to treat instable
      fractures of the trochanteric region with the PFN.

PMID- 16103954
TI  - [New osteosynthesis techniques for the treatment of distal femoral fractures].
AB  - The treatment of distal femoral fractures was for a long-time associated with
      high complication rates. Although implants and surgical techniques were improved,
      plate osteosynthesis and intramedullary nailing suffered from considerable rates
      of infection, non-union und malalignment. Attention to the soft tissue envelope
      by "biological" osteosynthesis and minimally invasive approaches resulted in
      decreased complication rates. Out of this movement grew the concept of minimal
      invasive plating with an internal fixator -- the LISS-DF (Less Invasive
      Stabilization System -- Distal Femur) -- and the retrograde nailing concept. This
      article should give a review about these two new techniques for the treatment of
      distal femoral fractures. Indications, the clinical use and the aftercare will be
      discussed.

PMID- 16103955
TI  - [Stage-based treatment by partial meniscectomy, meniscal refixation and
      transplantation].
AB  - Clinical and experimental studies have demonstrated that the meniscus is
      important for normal knee function. Loss of meniscus results in abnormal load
      transmission across the knee and may lead to degenerative joint disease.
      Preservation of meniscal tissue is therefore important. About 10 % of all
      meniscal tears are repairable. The most successful repairs occur in younger
      patients who have an acute, vertical tear in the vascular portion of the
      meniscus. Currently, arthroscopic meniscal repair procedures include the inside
      out, the outside-in and the all-inside technique. Vertical suture techniques are
      superior to horizontally placed sutures. From a biomechanical point of view, 2-0
      to 1 sutures are recommended for suture repair. Various meniscus implants are
      also available for meniscal repair. The initial fixation strength of the implants
      is lower compared to vertical sutures. A combination of suture techniques and
      implants might be a treatment option in posterior meniscal lesions. The collagen
      meniscus implant has been designed to support tissue ingrowth after segmental
      medial meniscectomy. Although fibrocartilage matrix formation has been shown,
      long-term clinical follow-ups are still required. Meniscal allograft
      transplantation may be indicated in limited situations. Younger patients with
      meniscal deficiency due to previous meniscectomy who have only early arthrosis,
      normal axial alignment, and a stable knee may currently considered appropriate
      candidates for meniscal transplantation.

PMID- 16103956
TI  - [Computer-assisted knee surgery, what can we expect?].
AB  - Navigation systems for operative assistance in knee joint surgery have been
      established in the last 5 years. Among the large number of variable systems, the
      image-free kinematic systems have won widespread acceptance. The C-arm based
      systems are not superior to the image-free systems. The CT-based systems are
      advantageous in completely destroyed joints (with marked joint erosion) or
      advanced congenital or traumatic deformities. The intraoperatively-performed Iso
      C (3D) technique presents data sets in CT-quality, but because of its small data
      volume currently is limited to the reconstruction of articular surfaces following
      fractures. The use of image-free navigation in resurfacing knee arthroplasty is
      in the meantime beyond controversy whereby deviations in the mechanical axis from
      normal values can be significantly reduced. For high tibial osteotomies
      navigation modules will be soon available for marketing. However, with these
      modules, intraoperative imaging is indispensable, but it will be image-free in
      the future. The early clinical results are promising. Cruciate ligament
      navigation is not yet a clinical standard be-cause of the considerable associated
      time expenditure. The appropriate modules are still under development.

PMID- 16103957
TI  - [Significance and technique of autologous chondrocyte transplantation].
AB  - The bad risk for an early onset of osteoarthritis in the knee increases with the
      size of a cartilage defect. A collateral meniscus- or ligament-tear will enforce
      this hazard in addition. In order to avoid such a development, relevant full
      thickness cartilage defects should be reconstructed biologically and attendant
      meniscus- or ligament-tears as well as varus- or valgus deformities should be
      treated. A number of studies, including some prospective-randomized trials, have
      shown that autologous chondrocyte transplantation (ACT) is the most reliable
      procedure for a surgical treatment of full-thickness cartilage defects larger
      than 4 cm (2) in adults. One disadvantage of ACT is the extensive approach to the
      joint and often a hypertrophy of the repair tissue. To solve these problems, some
      different biomaterials for a matrix-assisted ACT have been developed. The
      scaffold we use has a covering membrane upside and a collagen-sponge carrying the
      chondrocytes. By means of special surgical instruments a minimally invasive
      implantation is possible, reducing the side-effects of an extensive approach.
      Animal studies showed the regeneration of a hyaline cartilage using our described
      system. However, results of current clinical studies with the different scaffolds
      must be awaited before an universal application of matrix-assisted ACT can be
      recommended.

PMID- 16103958
TI  - [The MacIntosh extra-articular knee stabilisation procedure -- an alternative
      after failed ACL reconstruction?].
AB  - Chronic knee instability after loss of the ACL and failed ACL reconstruction is a
      great problem for the patient and a complex treatment challenge. Minimizing the
      feeling of instability is the most important issue for the patient. In case of
      lack of autologous material for reconstruction and lesions of the knee joint
      because of performed intra-articular procedures, extra-articular techniques are
      an alternative. In the modified MacIntosh procedure, we tie a strip of iliotibial
      tractus around the LCL and attach it to the ventrolateral tibial head by screw.
      Postoperatively, we begin physiotherapy under full weight bearing. Range of
      motion is limited to 0/0/90 degrees for six weeks. Between 1996 and 2000, nine
      patients who underwent surgery using the modified Macintosh technique, were
      evaluated prospectively. The mean follow-up was 11.4 months (6-36 months). We
      evaluated changes concerning pivot-shift and Lachman-test and documented Lysholm-
      and Tegner-activity-score pre- and postoperatively. We also registered sporting
      ability. The pivot shift remained positive, while the anterior drawer, documented
      by Lachman-test, could be reduced surgically. Lysholm- and Tegner-scores improved
      significantly. Preoperatively, the mean Tegner-score was 1.44 (0-3), mean Lysholm
      score 55.55 points (14-88), respectively. At follow-up examination, scores had
      improved to 3.55 (3-4) and 82.44 points (69-95), respectively, resulting in a p
      value of .007 for the Tegner-, and p = 0.008 for the Lysholm-score. Our surgical
      treatment could reduce the subjective feeling of instability in all cases. All
      patients could participate in sports activities at time of follow-up. Our results
      show, that extra-articular surgical procedures are adequate alternative methods
      of treatment in cases of persistent knee instability after recurrent failure of
      ACL reconstruction. The modified MacIntosh procedure described in this study
      shows encouraging results at medium-term follow-up. The technique is easy to
      perform and less traumatising for the knee joint.

PMID- 16103959
TI  - [New-bone formation by osteogenic protein-1 and autogenic bone marrow in a
      critical tibial defect model in sheep].
AB  - AIM: Osteogenic Protein-1 (OP-1) is known to be a very potent osteoinductive
      growth factor. However, experimental studies using critical-size defect models in
      the weight-bearing lower extremity show non-uniform results. Therefore, we
      studied the osteoinductivity of OP-1 in a tibial worst-case defect model in
      sheep. Potential improvement of OP-1 induced new bone formation using a composite
      graft with autogenous bone marrow was to be investigated. METHOD: In 19 sheep a 5
      cm segmental defect of the tibial diaphysis was treated by intramedullary nailing
      and filled with the following implants: 5 mg OP-1 + inactivated demineralized
      bone matrix (group 1; n = 6); 5 mg OP-1 + inactivated demineralized bone matrix +
      5 ml autogenous bone marrow (group 2; n = 5); autogenous cancellous bone (group
      3; n = 4), or inactivated demineralized bone matrix + 5 ml autogenous bone marrow
      (group 4; n = 4). RESULTS: In total, 3 out of 10 defect sites treated with OP-1
      were completely bridged radiographically by 12 weeks. Initially, x-rays showed
      accelerated new bone formation by use of the composite grafts containing OP-1 and
      autogenous bone marrow. However, 12 weeks post surgery 3D-CT-volumetry could not
      detect significant differences of new bone formation within the defect sites
      treated by OP-1 with or without bone marrow, while new bone formation by
      autogenous cancellous bone was better than by OP-1. CONCLUSION: In our worst case
      defect model, the osteoinductive potential of OP-1 is initially accelerated but
      12 weeks post surgery not increased when combined with autogenous bone marrow
      transplantation. So far, critical segmental bone defects of the weight-bearing
      lower extremity can not be bridged regularly in our model by use of OP-1.
      Therefore, for the treatment of such critical defects with rotational instability
      the examined application device of OP-1 can not yet be recommended.

PMID- 16103960
TI  - [The use of a thermomechanical cleaning procedure for removal of residual
      particles of corund blasted or glass bead peened implants in total hip
      arthoplasty].
AB  - INTRODUCTION: Shot peening and grit blasting techniques are used to modify
      surfaces of hip endoprostheses. Alumina blasting techniques using highly pure
      corund (Al (2)O (3)) particles create a rough surface of Titanium implants to
      achieve a better osteointegration in cementless total hip arthroplasty. An
      increasing number of publications in maxillo-facial-surgery and orthopedic
      surgery show that there is a significant contamination with remnants on corund
      blasted surfaces. To our knowledge no previous study analysed the effects of
      cleaning procedures of hip endoprostheses in respect to glass beads and Al (2)O
      (3) remnants. MATERIAL AND METHOD: The surface of the flexible anisotropic Vector
      cup and the stiff modular MRP-Titan stem (one implant each) were analysed with
      respect to Al (2)O (3) or glass particles before and after the cleaning
      procedure. The implants were cleaned using an ultrasound bath for 10 or 20
      minutes under nitrogen cooling or simple ultrasound bath with water. A field
      emission scanning electron microscopy (LEO 1525) was used for the detection of
      the particles on the implant surface with a backscattered electron detector. The
      proportion of the surface covered with particles was determined with an imaging
      analyze software (analySIS, Soft Imaging System GmbH). RESULTS: A reduction of
      corund particles on the surface of the flexible anisotropic Vector cup of up to
      5.2 % (from 40.0 % to 34.8 %) after 10 minutes nitrogen cooling was achieved. A
      reduction of corund particles on the surface of the stiff MRP-Titan stem of up to
      2.2 % (from 38.8 % to 36.6 %) was observed after 20 minutes of non cooled
      ultrasound bath whereas a reduction up to 3.2 % (from 25.8 % to 22.6 %) of glass
      particles after 10 minutes of nitrogen cooled ultrasound bath was detected.
      CONCLUSION: With the cleaning procedure tested only incomplete removal of just
      the small glass and Al (2)O (3) particles is possible. Further research is needed
      to reduce or even avoid residual particles in total hip arthoplasty.

PMID- 16103961
TI  - [Results of surgical treatment in ampullary and pancreatic carcinoma and its
      prognostic parameters after R0-resection].
AB  - INTRODUCTION: Resection is currently the only established reasonable therapeutic
      option with curative potential in pancreatic and ampullary carcinoma. The aim of
      the study was i) to analyze value and results of surgical therapy and ii) to
      detect the prognostic parameters, which determine significantly higher survival
      rates. METHODS: Two-hundred-twenty patients with pancreatic and ampullary
      carcinoma (mean age, 61.4 years; 104 females/116 males) underwent surgery.
      Histologic investigation revealed 19 carcinomas of the papilla of Vater and 201
      ductal pancreatic carcinomas. In 126 patients, stage IV a or b tumors were found,
      in addition, stage I (n =26), II (n = 17) and III (n = 51). Survival-rate was
      determined according to the method by Kaplan/Meier. Survival was compared using
      log-rank test. Association of several or multiple parameters with survival was
      tested using Cox model. RESULTS: Hundred-ten patients underwent tumor resection
      with primary curative intention (50 %): 96 resections of the pancreatic head, 2
      total pancreatectomies and 12 left resections of the pancreas. R0-resection was
      achieved in 94 patients (42.7 %), whereas intervention was classified R1 in 10
      and R2 in 6 cases. In addition, 60 palliative interventions (28
      gastroenterostomies, 17 biliodigestive anastomoses, 15 anastomoses at both sites)
      and 50 explorative laparotomies were performed. In 42.3 % of patients,
      postoperative complications were found, but only 12/220 individuals died (overall
      letality, 5.4 %). Postoperative letality of curative pancreatic resections was
      3.6 % (palliative intervention, 6.7 %; explorative laparotomy, 8.8 %). Five-year
      survival-rate of carcinoma of the papilla of Vater and pancreatic carcinoma was
      73.3 % and 16.2 %, respectively (median survival time was 66.0 and 14.0 months,
      respectively). Taken together all other interventions, median survival time
      ranged between 4.0 (palliative intervention) to 10.0 months (R1-resection). No
      patient survived 5 years. Therefore, the most relevant prognostic factor was R0
      resection. In addition, prognosis after successful R0-resection is determined
      significantly by tumor site, stage of the tumor (according to UICC), T- and N
      category. CONCLUSION: Resection of pancreatic and ampullary carcinoma according
      to oncological criteria with tumor-free margins can be considered a treatment
      option with curative intention and potential. Despite relative high postoperative
      morbidity, only a low mortality rate was observed. The 5-year survival-rate of
      16.2 % in ductal pancreatic carcinoma underlines the demand for the development
      of effective multimodal therapeutic concepts. Interventions with primary
      palliative intention or resections with microscopically or macroscopically
      detectable tumor residual in situ lead to no significant or only marginal
      prolongation of survival time. Such interventions in patients with pancreatic
      carcinoma are no reasonable treatment alternative. They are of value only for
      treatment of tumor-associated complications and problems.

PMID- 16103962
TI  - [Studies on low protein C-expression in severe sepsis].
AB  - OBJECTIVES: Low concentration of protein C in severe sepsis may be associated
      with increased morbidity and mortality. The present study was designed to clarify
      to what extent there are differences in the time course of plasma concentrations
      of protein C in patients with systemic inflammatory response syndrome or patients
      with severe sepsis. In addition, the cause of decreased expression of protein C
      in severe sepsis was examined. METHODS: 32 patients with severe sepsis and 10
      patients with systemic inflammatory response syndrome admitted to a surgical
      intensive care unit were enrolled in the study. While the patients stayed in the
      intensive care unit protein C plasma concentrations and the clotting factors
      thrombin-antithrombin-complex and factor VII were determined twice weekly.
      RESULTS: Comparing patients with severe sepsis and systemic inflammatory response
      syndrome there was no significant difference concerning plasma levels of protein
      C, thrombin-antithrombin-complex and factor VII. In contrast, surviving patients
      with severe sepsis exhibited significant higher protein C levels compared to non
      survivors. In addition, significant lower plasma levels of thrombin-antithrombin
      complex were determined in survivors compared to non-survivors. However, factor
      VII displayed no significant group difference. CONCLUSIONS: Surviving patients
      with severe sepsis exhibited higher plasma concentrations of protein C than
      patients who died during severe sepsis. The lower plasma concentrations of
      protein C in non-survivors may be caused by an increased turnover of protein C
      served as endogenous anticoagulant in sepsis associated activation of
      coagulation.

PMID- 16103963
TI  - [Is the thyroidectomy a surgical standard procedure for therapy of Graves'
      disease?].
AB  - Surgery is an important therapeutic option in the treatment of Graves' disease.
      Nevertheless it is still controversial discussed wether the extent of resection
      correlates with the rate of surgical complications and the therapeutic success.
      Therefore we performed a retrospective analysis on 75 surgically treated
      patients. 58 of these 75 patients were examined after a median interval of 34.2
      months. The examination focussed on the appearance of temporary and permanent
      palsy of the recurrent laryngeal nerve, hypoparathyroidism, recurrences, and on
      the postoperative course of thyroid-stimulating-hormone-receptor antibody (TSH
      ab) titers. Total thyroidectomy has been performed in 51 and bilateral resection
      with a remnant thyroid volume less than 2 ml each side in 24 patients. We could
      not confirm a significant difference concerning the postoperative complication
      rates between both groups. In the bilateral resection group we saw 3 cases of
      recurrent goitre and a more unfavourable course of TSH-ab titers than in the
      thyroidectomy group. For these reasons we propose the total thyroidectomy as
      surgical standard procedure for therapy of Graves' disease.

PMID- 16103964
TI  - [Paraneoplastic lupus anticoagulans syndrome].
AB  - The antiphospholipid antibody syndrome (Lupus anticoagulans syndrome) is a rare
      form of coagulopathy due to the presence of autoantibodies against phospholipids
      or phospholipid-binding protein cofactors that can lead to vascular thrombosis.
      We report the case of a 57-year-old female patient presenting with decompensated
      duodenal stenosis due to a pancreatic tumor. Perioperative testing of coagulation
      markers revealed with 26 % a strongly decreased Quick-Test and with 81.4 s a
      prolonged partial thromboplastin time that persisted despite intravenous
      application of 80 mg vitamin K (Konakion) and 10 units of fresh frozen plasma.
      Subsequent screening for common causes of thrombophilia revealed antiphospholipid
      antibodies. Consequently, low molecular weight heparin (Dalteparin-Natrium) was
      administered perioperatively while a gastroenterostomy with entero-enterostomy
      was performed with uneventful postoperative course. With this presentation and an
      analysis of the contemporary literature we would like to discuss different
      aspects of Lupus anticoagulans syndrome.

PMID- 16103965
TI  - [Pericardial empyema due to oropharyngeal infection -- a rare entity].
AB  - Both the descending necrotizing mediastinitis (DNM) and the pericardial empyema
      are rare but life threatening situations, in which rapid aggressive surgical
      approach is important for the outcome. A 37-year-old man presented with reduced
      general health and new establishment of thoracal pain after an infection in the
      oropharyngeal region. The dissemination of the infection into the mediastinum
      (mediastinitis) diagnosed by clinic and radiography required surgical
      intervention. A pericardial empyema was detected intraoperatively. The patient
      was discharged home on the 14 (th) hospital day.

PMID- 16103966
TI  - [Hepatitis B and C risk factors in Germany--results of the national
      surveillance].
AB  - Collection of risk factor data is part of the national surveillance of hepatitis
      B and C in Germany. After modifications of risk factor surveillance had been
      implemented in September 2003, the response rate for data on risk factors
      increased markedly. For the period between September 2003 and August 2004,
      information on risk factors (at least one "yes" or "no" answer) was available for
      66% (1853) of all notified hepatitis B cases and for 67% (5813) of all notified
      hepatitis C cases. More than 30% of those hepatitis B cases occurred among risk
      groups for whom hepatitis B immunisation is recommended by the German Advisory
      Committee on Immunisation (STIKO). Of the hepatitis C cases with risk factor
      data, 40% reported previous or continuing injecting drug use (IDU). IDU was
      predominant among young men (78% among men, aged 15 to 29 years) and can explain
      the comparatively high incidence observed in young adults, especially among men.
      The impact of other risk factors (e. g. medical interventions) cannot be
      quantified without a proper control group. The results of this study demonstrate
      that--in addition to the hepatitis B immunisation of children and adolescents-
      vaccination coverage of specific risk groups, as defined by the STIKO, should be
      increased. Measures to prevent hepatitis C have to focus on intravenous drug
      users and clearly have to be intensified.

PMID- 16103967
TI  - [Contributions of the epidemiological cancer registries to the evaluation of
      mammography screening in Germany].
AB  - INTRODUCTION: Before the country-wide introduction of mammography screening,
      testing of the organised screening took place in Weser-Ems, Bremen and Wiesbaden.
      Important quality assurance parameters (carcinomas detected during checkup
      intervals, tumour stage distribution, breast cancer incidence rate, breast cancer
      mortality rate) are to be evaluated via epidemiological cancer registries. For
      the model region Weser-Ems (MSWE) the record linkage with the epidemiological
      cancer registry Lower Saxony (EKN) was successfully accomplished. The technical
      realisation and first comparison analyses for the development of breast cancer
      incidence and of tumour size are reported. MATERIAL AND METHODS: The target
      population of the MSWE was 22,600 women aged 50-69 years. They were invited since
      May 2002 to mammography screening with a screening interval of two years. The
      record linkage of 12,913 women who participated until February 2004 in the MSWE,
      was realised by the use of the control number system of the epidemiological
      cancer registries. The observation time was between 6 and 25 month (median: 15
      month). Reference population for comparison analyses were all women between 50
      and 69 years of the remaining governmental district Weser-Ems (255,000 women).
      RESULTS: In the first record linkage 96 screening-cases (ICD-10 C50 + D05) could
      be identified. Additionally six interval cancers were determined (time between
      screening and diagnosis in months: median 5.5; mean 7.7). The breast cancer
      incidence increased in the MSWE area and in the control-area, the rise in the
      MSWE area being higher. The increase was especially observed with the small
      tumours. Women with breast cancer diagnosed by screening: 19.8% in-situ-cancer
      and 18.8% very small tumours < = 10 mm. In the control area Weser-Ems this rate
      with 5.6% in-situ-cancer and 14.5% very small tumours, was relatively high,
      indicating the spread of opportunistic mammographies in absence of organised
      screening. CONCLUSION: First effects of mammography screening can be evaluated
      early by comparison between screening data and the data of population-based
      cancer registries. Using the control number system of the epidemiological cancer
      registries and comparison by pseudonyms the evaluation of quality assurance
      parameters of the MSWE can be realised in compliance with the data security law.
      The feedback of cancers, detected during checkup intervals is not covered by the
      cancer registry law. For the implementation of the guidelines for early
      recognition cancer legal adjustments will be necessary. This concept can be
      easily adapted to other screening programme.

PMID- 16103968
TI  - [Knowledge of colorectal cancer prevention in the Bavarian population above 50
      years--survey in two districts].
AB  - PURPOSE: Colorectal cancer is the second main cause of cancer death in Germany,
      although several measures related to primary prevention are described, and the
      utilisation of existing diagnostic tools (faecal occult blood test = FOBT,
      colonoscopy) is known to significantly decrease incidence and mortality. However,
      screening rates remain low in Germany, and insufficient knowledge of prevention
      possibilities is assumed to be responsible. The aim of this study was to
      investigate the knowledge related to colorectal cancer prevention in a Bavarian
      population, in the context of a regional public awareness campaign ("Active
      against Colorectal Cancer"). METHODS: 618 individuals between 50 and 90 ys of age
      participated in a telephone survey (m: 219, f: 399, 63.2 +/- 9.17 ys); the
      participants were inhabitants of two Bavarian districts. The questionnaire
      consisted of open-ended questions concerning preventive behaviour, colorectal
      cancer screening, risk factors, early warning signs and knowledge of colorectal
      cancer information. RESULTS: More than 80% of participants recalled healthy diet
      as a possible protective factor against colorectal cancer; a distinctly smaller
      percentage, however, could correctly define concrete dietary factors: e. g.,
      fruit and vegetables were named by 54.5%. 66% of participants knew that unusual
      rectal bleeding might be a warning sign of cancer. Colonoscopy was the screening
      test that was most frequently recalled (61.5%); fewer participants named FOBT
      (32.8%) and rectal examination (11.5%). The results demonstrate that for many
      knowledge items, females proved to be significantly better informed than males.
      The most frequent sources of colorectal cancer information were newspapers,
      magazines, television and/or radio (named by 76.7%), as well as physicians and
      pharmacies (45.1%). 11.5% of participants attended the regional public awareness
      campaign "Action against colorectal cancer"; this subgroup had a better knowledge
      of some aspects related to colorectal cancer prevention. CONCLUSION: Evidently,
      the interviewed Bavarian population of 50 years or older lack knowledge of risk
      or protection factors for colorectal cancer. Knowledge of existing screening
      tests was also poor. These findings can serve as starting point for information
      campaigns tailored for target groups.

PMID- 16103969
TI  - [Smoking cessation during treatment of alcohol dependence in drug and alcohol
      rehabilitation centres--a review].
AB  - PURPOSE: Review of the international literature on smoking cessation with smokers
      having a concurrent alcohol abuse disorder. The three aims are: 1. discussion of
      the pros and cons of concurrent smoking cessation and treatment of alcohol use
      disorder, 2. smoking cessation strategies and 3. description of national and
      international studies evaluating smoking cessation interventions with patients
      who are at the same time treated for their alcohol abuse disorder. METHOD: The
      results are collected on the basis of an extensive literature research in
      PsychInfo, Science Direct and Medicine. RESULTS: Considering the pros and cons,
      it can be concluded that smoking cessation should be offered to this subgroup of
      high risk smokers. The open question is which kind of interventions are
      effective. Intervention strategies should consist of a multi-level approach
      including structural as well as person-specific components. Evaluation studies
      show that a 12% abstinence rate at one year follow-up can be achieved in case of
      an intensive intervention in combination with a restrictive tobacco policy.
      Alcohol abstinence is not jeopardised by a concurrent smoking cessation, when
      smoking cessation is voluntary. CONCLUSIONS: On the basis of empiric research the
      common arguments against smoking cessation within the subgroup of alcohol
      addicted smokers cannot be maintained on the basis of empiric research.
      Rehabilitation centres treating substance abuse disorders provide an excellent
      setting for the treatment of nicotine dependence. Interventions should include
      structural as well as subgroup-specific components.

PMID- 16103970
TI  - [Pharmaceutical reference pricing in Germany: definition of therapeutic groups,
      price setting through regression procedure and effects].
AB  - The German reference pricing system defines a reimbursement threshold for groups
      of pharmaceuticals. Pharmaceuticals are grouped according to certain criteria by
      the Federal Joint Committee. To make different active ingredients comparable, so
      called reference values are defined. Subsequently, the federal association of
      sickness funds sets reference prices using a regression procedure. However, the
      impact of the reference price system is limited. On the one hand there is a
      strong incentive for pharmaceutical companies to decrease prices to the reference
      price. On the other hand there is no incentive for further price reductions.
      Additionally, only one part of the pharmaceutical market is affected by reference
      pricing. Therefore the instrument has only managed to lower pharmaceutical
      expenditure in the short run. For sustainable long-term cost containment the use
      of other regulatory instruments is necessary. Nevertheless, compared to other
      instruments of price-regulation, reference pricing seems to be a good alternative
      to control pharmaceutical prices, since rationing is kept as little as possible.

PMID- 16103971
TI  - [A programme to assist close relatives and lifelong partners in caring for
      persons suffering from depressions or schizophrenic disorders].
AB  - OBJECTIVE: Lifelong partners or close relatives of persons suffering from mental
      disorders will naturally step in to help by assuming a great variety of tasks. By
      witnessing their relative's illness on a daily basis, they are exposed to many
      burdens with a negative impact on their own well-being. Hence, supporting the
      relatives of persons with mental disorders appears imperative. While there are
      various approaches to working with relatives, there are hardly any specific
      programmes for working with certain groups of relatives such as spouses, children
      or siblings. METHODS: Basing on a discussion of the various approaches to looking
      after relatives, development of a programme is described aimed at specifically
      supporting spouses of persons suffering from depression or schizophrenia.
      RESULTS: The concept of our programme is presented and results of its evaluation
      by participants are reported. CONCLUSION: The initial experiences with the
      support programme are quite promising. An evaluation of its effects, based on a
      case-control-design, is currently under way.

PMID- 16103972
TI  - [Integrated intensive treatment of tinnitus: method and initial results].
AB  - In recent years, no major advances have been made in understanding the mechanisms
      underlying the development of tinnitus. Hence, the present therapeutic strategies
      aim at decoupling the subconscious from the perception of tinnitus. Mindful of
      the lessons drawn from existing tinnitus retraining and desensitisation
      therapies, a new integrated day hospital strategy of treatment lasting 7-14 days
      has been developed at the Charite Hospital and is presented in the present paper.
      The strategy for treating tinnitus in the proximity of patient domicile is
      designed for patients who feel disturbed in their world of perception and their
      efficiency due to tinnitus and give evidence of mental and physical strain. In
      view of the etiologically non-uniform and multiple events connected with
      tinnitus, consideration was also given to the fact that somatic and psychosocial
      factors are equally involved. Therefore, therapy should aim at diagnosing and
      therapeutically influencing those psychosocial factors that reduce the hearing
      impression to such an extent that the affected persons suffer from strain. The
      first results of therapy-dependent changes of 46 patients suffering from chronic
      tinnitus are presented. The data were evaluated before and after 7 days of
      treatment and 6 months after the end of treatment. Immediately after the
      treatment, the scores of both the tinnitus questionnaire (Goebel and Hiller) and
      the subscales improved significantly. These results were maintained during the 6
      month post-treatment period and even improved.

PMID- 16103973
TI  - [Possible effects of climatic changes on the spread of malaria tropica--results
      of a strategical simulation].
AB  - The Earth's surface is presently undergoing a period of global warming-up, which
      increases the likelihood of a spread of malaria tropica. A reliable prognosis
      would be important for efficient prevention by initiating appropriate counter
      measures well in time. The following paper presents simulations of the effects of
      climatic changes on the spread of malaria. We do not specifically aim at
      obtaining concrete data for a particular region; rather, we are concerned with
      gaining an insight into the complex interrelations between global environment
      changes and the spread of malaria.

PMID- 16103976
TI  - Epidemiology and natural history of hepatitis B.
AB  - Hepatitis B virus (HBV) is a common viral pathogen that currently infects an
      estimated 4 million people worldwide, including 400 million who have chronic
      infection. Persons with chronic HBV infection are at a lifelong risk of
      developing hepatocellular carcinoma (HCC) or cirrhosis, or both. Many persons
      with HBV are unaware that they carry the infection, and, of those who are
      chronically infected, only a minority receives routine, scheduled follow-up to
      monitor their disease status. Persons from high-risk populations, especially
      immigrants from nations where hepatitis B is highly endemic, should be tested for
      HBV seromarkers and should be vaccinated if they are found to be negative. The
      natural history of chronic HBV is a dynamic one: patients can fluctuate between
      periods of active liver inflammation and periods of inactive disease. Disease
      progression is influenced by various factors, including viral genotype and
      specific mutations, demographic features, concurrent viral infections, and social
      and environmental factors. Recent data suggest that antiviral therapy can
      decrease the risk of liver decompensation and liver-related death and reduce the
      risk of HCC in selected individuals with active liver disease and severe
      fibrosis. Persons identified with chronic HBV infection need lifelong, regular
      monitoring for the development of active liver disease and HCC.

PMID- 16103977
TI  - Molecular virology and the development of resistant mutants: implications for
      therapy.
AB  - Two of the key events in the viral life cycle of the hepatitis B virus (HBV)
      involve (1) generation from genomic DNA of the covalently closed circular DNA
      transcriptional template and (2) reverse transcription of the viral pregenomic
      RNA to form the HBV DNA genome. Because the virus employs reverse transcription
      to copy its genome, mutant viral genomes are found frequently. Particular
      selection pressures, both endogenous (host immune clearance) and exogenous
      (vaccines and antivirals), readily select out these escape mutants. The
      introduction of nucleoside/nucleotide analogue therapy has seen the emergence of
      drug resistance as the major factor limiting drug efficacy. The development of
      drug resistance is not unexpected if viral replication continues in the setting
      of ongoing treatment, especially monotherapy. Thus, prevention of resistance
      requires the adoption of strategies that effectively control virus replication.

PMID- 16103978
TI  - Current treatment of chronic hepatitis B: benefits and limitations.
AB  - Nucleoside analogue therapy allows safe, long-term suppression of hepatitis B
      virus (HBV) and is a major milestone in the treatment of chronic hepatitis B.
      Entecavir has recently been approved by the U.S. Food and Drug Administration and
      is not only more potent than lamivudine and adefovir, but it is also associated
      with a very low rate of drug resistance. Peginterferon, which has been shown to
      be more potent than conventional interferon, has recently been licensed in Europe
      and in the United States. Despite these advances, however, the clinician still
      faces several challenges in treating this relatively complex disorder.
      Controversies and unresolved issues remain, including the question of whether the
      thresholds for alanine aminotransferase and HBV DNA levels recommended in the
      published treatment guidelines are too restrictive. Another complication is the
      differing levels of sensitivity and dynamic range of the assays for serum HBV
      DNA. Finite courses of treatment are associated with low rates of virologic
      response, but drug resistance occurs when nucleoside analogue monotherapy is used
      long term. The role for combination therapy remains unclear. Much has been
      accomplished over the past decade, but much remains to be done.

PMID- 16103979
TI  - Clinical trial results of new therapies for HBV: implications for treatment
      guidelines.
AB  - Currently approved treatments for chronic infection with hepatitis B virus (HBV)
      are limited by low rates of sustained response, side effects, and in some cases,
      the emergence of drug resistance. Thus, new treatments, characterized by more
      potent antiviral effects less toxicity, and minimal or no risk of resistance, are
      needed. During the last few years, several agents have been developed that have
      increased potency and reduced potential for resistance--among them, entecavir and
      pegylated interferons. In addition, several novel anti-HBV agents recently
      evaluated in phase II clinical trials, such as tenofovir, clevudine, telbivudine,
      pradefovir, and valtorcitabine, appear to be promising agents for the treatment
      of chronic hepatitis B. This article describes the clinical experience with new
      antiviral agents and the implications of the trial results for practice
      guidelines.

PMID- 16103980
TI  - Prevention and surveillance of hepatitis B virus-related hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is associated with hepatitis B virus (HBV)
      infection in approximately 50% of cases, although the oncogenic mechanisms of HBV
      are not well understood. Vaccination for HBV has successfully lowered the rates
      of both HBV infection and HCC. Once chronic HBV infection is established, the
      objective of antiviral treatment is to prevent disease progression to liver
      cirrhosis or HCC, or both. Studies have found HBV DNA level to be a strong
      predictor for the development of cirrhosis and HCC, irrespective of the status of
      viral and biochemical factors. This article reviews recent clinical trials
      evaluating sustained viral suppression with interferon alfa and lamivudine. The
      results support the need to reduce viral load as an important therapeutic goal.
      For HCC not prevented by these measures, surveillance using ultrasonography and
      serum alpha-fetoprotein assay every 3 to 6 months is able to detect HCC at an
      earlier stage and allows curative therapy with survival benefit.

PMID- 16103981
TI  - Management of HBV/HIV-coinfected Patients.
AB  - Coinfection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV)
      is common as a result of shared routes of transmission, especially in high-risk
      groups such as injection drug users and persons with hemophilia. HIV is known to
      influence the natural history of HBV, hastening progression to end-stage liver
      disease and cirrhosis. Antiretroviral therapy for HIV, and associated immune
      reconstitution, may result in immune-mediated liver damage as HBV-infected
      hepatocytes are targeted. This can lead to liver enzyme elevations that may be
      misattributed to drug-related toxicity. Thus, it is important that HIV-infected
      patients be tested for HBV and that clinicians be aware of the possibility of
      atypical serologic markers of HBV in HIV-infected patients. In managing
      coinfected patients, control of HIV is the priority. In patients with controlled
      HIV who are candidates for HBV therapy, the goals are the same as in the HBV
      monoinfected population: hepatitis B e antigen seroconversion, liver enzyme
      normalization, and HBV DNA suppression. Treatment options include interferon
      based regimens, lamivudine, adefovir, tenofovir, and entecavir. All of these
      agents have been shown to be relatively effective in HBV-monoinfected patients.
      However, few randomized, controlled HBV treatment trials have been conducted in
      coinfected subjects, and thus additional studies are warranted.

PMID- 16103986
TI  - Aneuploidy screening in coelomic samples using fluorescence in situ hybridisation
      (FISH).
AB  - OBJECTIVES: Coelocentesis is the earliest invasive prenatal diagnostic procedure
      that has recently been used in ongoing pregnancies to identify single gene
      defects. Aneuploidy screening has not yet been performed in ongoing pregnancies
      following coelocentesis, but experimental studies have demonstrated the ability
      of determining the copy number of chromosomes 13, 18, 21, X and Y in uncultured
      coelomic samples, by FISH or PCR. The aim of this study was to extend previous
      studies and investigate the feasibility of analysing uncultured coelomic fluid
      samples for 11 chromosomes using fluorescence in situ hybridisation (FISH).
      METHODS: Coelocentesis was performed in 12 singleton pregnancies at 6 to 9 weeks
      of gestation immediately before surgical termination of pregnancy. Fluorescence
      probes for chromosomes 3,7,9,13,16,17,18,21,22, X and Y were applied on
      uncultured coelomic-fluid samples and placental tissue. In cases where coelomic
      cells were not of a sufficient amount, chromosomes X and Y were analysed in a
      second layer of hybridisation. RESULTS: Successful analysis by FISH was possible
      in all cases and the results from the coelomic fluid were concordant with those
      from the analysis of placental tissue and obtained within a few hours of
      receiving the samples. Problems associated with limited cell numbers were
      overcome by the application of a second layer of FISH. This sequential approach
      has also enabled accurate identification of maternal-cell contamination in male
      samples. CONCLUSION: Analysis of 11 chromosomes using FISH in coelomic fluid
      samples is feasible and it has the potential to be applied for rapid aneuploidy
      screening, should coelocentesis be used clinically as an early, invasive prenatal
      diagnostic tool.

PMID- 16103987
TI  - The first synthesis of chiral PNA monomer-cyclen conjugates.
AB  - A synthetic route to novel chiral PNA monomer-cyclen conjugates was described for
      the first time, the targeted products were obtained in high yields under mild
      reaction conditions. The preliminary results demonstrated that the uracil-PNA
      monomer-cyclen conjugates can rapidly bind Zn2+ in aqueous solution, and the
      structure of the Zn(II) complex was confirmed facilely by HRMS spectra, 1H NMR
      spectra and elemental analysis.

PMID- 16103988
TI  - Small peptides, big world: biotechnological potential in neglected bioactive
      peptides from arthropod venoms.
AB  - Until recently, a toxinologist's tasks involved the search for highly toxic or
      lethal toxins in animal venoms that could explain the harmful effects in
      clinically observed symptoms. Most of these toxins were put on evidence using a
      function to structure approach, in which a biological phenomena observation
      usually guided the isolation and characterization of the causative molecule.
      Paving this way, many toxins were promptly purified because of their readily
      observed effect. Nevertheless, small molecules with micro-effects that are not
      easily visualized can be relatively neglected or poorly studied. This situation
      has changed now with the advent of the sensitivity, resolution and accuracy of
      techniques such as mass spectrometry and proteomic approaches used in toxinology.
      Taking advantage of these methodologies, small peptides with 'newly exploited'
      biological activities such as vasoactive, hormone-like, antimicrobial and others
      have been recently given much more attention, enlarging the known repertoire of
      bioactive molecules found in animal venoms. This article aims to review current
      knowledge on small biologically active peptides (<3 kDa) found in arthropod
      venoms and discuss their potentialities as new drug candidates or therapeutic
      lead compounds.

PMID- 16103989
TI  - Function and therapeutic potential of host defence peptides.
AB  - Cationic host defence (antimicrobial) peptides are an important component of the
      innate immune systems of a wide variety of plants, animals, and bacteria.
      Although most of these compounds have direct antimicrobial activities under
      specific conditions, a greater appreciation for the diversity of functions of
      these molecules is beginning to develop in the field. In addition to their
      directly antimicrobial activities, they also have a broad spectrum of activity on
      the host immune system, with both pro-inflammatory and anti-inflammatory effects
      being invoked. Increasingly sophisticated approaches to understand the role of
      host defence peptides in modulating innate immunity are already serving to guide
      the development of novel therapeutics.

PMID- 16103990
TI  - 1H NMR assignment and secondary structure of recombinant RGD-hirudin.
AB  - The conformation of a new recombinant RGD-hirudin, which has the activities of
      anti-thrombin and anti-platelet aggregation, was investigated by multi
      dimensional NMR spectroscopy. The 1H NMR spectra of this protein are assigned in
      a sequential manner by using a combination of 2D NMR techniques to demonstrate
      through-bond and through-space (<5 A) connectivities. The secondary structure of
      recombinant RGD-hirudin was deduced from chemical shift indices, sequential NOEs
      and 3J(HNalpha) coupling constants. The results show that the recombinant RGD
      hirudin has two anti-parallel beta-sheets and no alpha-helix, and also that the
      Arg-Gly-Asp (RGD) binding motif of this protein is located at the end of a long
      arm, which consists of two anti-parallel beta-strands (residues 26-31 and 36-41).
      As the strands are connected by a beta-turn, the recombinant RGD-hirudin acquires
      high flexibility and inhibits platelet aggregation more effectively.

PMID- 16103991
TI  - Complete assignments of 1H and 13C NMR spectral data for benzylidenebenzyl
      butyrolactone lignans.
AB  - The structures of three benzylidenebenzyl butyrolactone lignans (gossypifan,
      carthamogenin, and savinin) have been established on basis of 1H NMR and 13C NMR
      spectroscopic data. The 1H NMR and 13C NMR spectra of these lignans have been
      fully assigned by the use of techniques such as gCOSY, non-edited gHSQC, and
      gHMBC. Complete assignment and most homonuclear hydrogen coupling constant
      measurements were performed, also providing enough data for the determination of
      the relative stereochemistry.

PMID- 16103992
TI  - C-terminal N-alkylated peptide amides resulting from the linker decomposition of
      the Rink amide resin: a new cleavage mixture prevents their formation.
AB  - Decomposition of the resin linkers during TFA cleavage of the peptides in the
      Fmoc strategy leads to alkylation of sensitive amino acids. The C-terminal amide
      alkylation, reported for the first time, is shown to be a major problem in
      peptide amides synthesized on the Rink amide resin. This side reaction occurs as
      a result of the Rink amide linker decomposition under TFA treatment of the
      peptide resin. The use of 1,3-dimethoxybenzene in a cleavage cocktail prevents
      almost quantitatively formation of C-terminal N-alkylated peptide amides.
      Oxidized by-product in the tested Cys- and Met-containing peptides were not
      observed, even if thiols were not used in the cleavage mixture.

PMID- 16103993
TI  - Synthetic RGD-containing alpha-helical coiled coil peptides promote integrin
      dependent cell adhesion.
AB  - Integrin receptors are the main mediators of cell adhesion to the extracellular
      matrix. They bind to their ligands by interacting with short amino acid
      sequences, such as the RGD sequence. Soluble, small RGD-based peptides have been
      used to block integrin-binding to ligands, thereby interfering with cell
      adhesion, migration and survival, while substrate-immobilized RGD sequences have
      been used to enhance cell binding to artificial surfaces. This approach has
      several important medical applications, e.g. in suppression of tumor angiogenesis
      or stimulation of bone formation around implants. However, the relatively weak
      affinity of short RGD-containing peptides often results in incomplete integrin
      inhibition or ineffective ligation. In this work, we designed and synthesized
      several new multivalent RGD-containing molecules and tested their ability to
      inhibit or to promote integrin-dependent cell adhesion when used in solution or
      immobilized on substrates, respectively. These molecules consist of an oligomeric
      structure formed by alpha-helical coiled coil peptides fused at their amino
      terminal ends with an RGD-containing fragment. When immobilized on a substrate,
      these peptides specifically promoted integrin alphaVbeta3-dependent cell
      adhesion, but when used in solution, they blocked alphaVbeta3-dependent cell
      adhesion to the natural substrates fibronectin and vitronectin. One of the
      peptides was nearly 10-fold more efficient than fibronectin or vitronectin in
      promoting cell adhesion, and almost 100-fold more efficient than a linear RGD
      tripeptide in blocking adhesion. These results indicate that alpha-helical coiled
      coil peptides carrying an amino-terminal RGD motif can be used as soluble
      antagonists or surface-immobilized agonists to efficiently inhibit or promote
      integrin alphaVbeta3-mediated cell adhesion, respectively.

PMID- 16103994
TI  - Characterization of Alzheimer paired helical filaments by electron microscopy.
AB  - We show how electron microscopy can be used to answer several critical issues in
      neurodegenerative disorders that course with the formation of aberrant
      filamentous structures. Thus, electron microscopy is a useful technique to study
      in vitro assembly of pathogenic proteins, to map the regions involved in filament
      formation, as well as to detect by immunoelectron microscopy which proteins bind
      to the filaments. Furthermore, electron microscopy is the main technique used to
      discover if an animal model develops fibrillar pathology and if those filaments
      are similar to those found in human patients. This review focuses on Alzheimer's
      disease and related tauopathies, although similar studies have been done with
      other neurodegenerative disorders as, for example, Huntington's disease.

PMID- 16103995
TI  - Evaluating triggers and enhancers of tau fibrillization.
AB  - Alzheimer's disease is characterized in part by the aggregation of tau protein
      into filamentous inclusions. Because tau filaments form in brain regions
      associated with memory retention, and because their appearance correlates well
      with the degree of dementia, they have emerged as robust markers of disease
      progression. Yet the discovery that mutations in tau protein can lead directly to
      filament and tangle formation in humans, and that filament formation is linked to
      neurodegeneration in model biological systems, suggests that tau aggregation may
      also contribute directly to degeneration in affected neurons. In this context,
      the mechanism of tau filament formation and its modulation by mutation and
      posttranslational modification is of fundamental importance. Here, recent
      progress on the molecular mechanisms underlying tau aggregation deduced from in
      vivo and in vitro experimentation is reviewed and a model rationalizing the
      effect of posttranslational and other structural modifications on assembly
      kinetics and thermodynamics is presented. We hypothesize that tau aggregation can
      be described as a heterogeneous nucleation reaction, where exogenous effectors,
      tau gene mutations, or other modifications that stabilize assembly-competent
      conformations of tau act to trigger the fibrillization reaction. In contrast,
      those that modulate postnuclear equilibria can enhance fibrillization by
      increasing the free energy difference between polymers and unincorporated
      monomers, resulting in stabilization of filaments at low bulk protein
      concentrations.

PMID- 16103996
TI  - Alzheimer paired helical filaments (PHFs) studied by high-resolution TEM: what
      can vertical Pt-C replication tell us about the organization of the pronase
      digested PHF core?
AB  - Untreated paired helical filaments (PHFs) and pronase-digested PHF-core filaments
      were stereoscopically imaged with a freeze-drying vertical platinum-carbon
      replication preparation method for TEM. The untreated PHF have an average wide
      region (W) = 22.8 +/- 2.4 nm, a narrow region (T) = 10.6 +/- 1.7 nm, and a
      helical turn period (L) = 78.6 +/- 13.4. The surfaces of the untreated PHF's
      fuzzy coat appears disorganized. The widths of the pronase-treated PHF-core
      filaments were significantly reduced (W(d) = 14.8 +/- 1.2 nm, T(d) = 5.7 +/- 1.0
      nm, and L(d) = 75.4 +/- 17 nm). The surfaces of the untreated PHF contained
      approximately 1.1 nm strands, the same size as tau monomer ( approximately 1.0
      nm). The pronase-digested PHF cores mostly contained approximately 1.6 +/- 0.3 nm
      strands although strand diameters ranged from 0.6-2.5 nm. The strands sometimes
      appear to be wrapped around the filament axis; less often, they appear to be
      roughly parallel to the PHF axis, and otherwise appear to be randomly oriented.
      Images of pronase-digested PHF core images are discussed in relation to the
      core's biochemical composition, its proposed beta structure, and structural
      subunit models. Images of the untreated and the pronase-digested PHF support a
      helical ribbon morphology.

PMID- 16103997
TI  - Structure and morphology of the Alzheimer's amyloid fibril.
AB  - Amyloid fibrils are deposited in a number of diseases, including Alzheimer's
      disease, Type 2 diabetes, and the transmissible spongiform encephalopathies
      (TSE). These insoluble deposits are formed from normally soluble proteins that
      assemble to form fibrous aggregates that accumulate in the tissues. Electron
      microscopy has been used as a tool to examine the structure and morphology of
      these aggregates from ex vivo materials, but predominantly from synthetic amyloid
      fibrils assembled from proteins or peptides in vitro. Electron microscopy has
      shown that the fibrils are straight, unbranching, and are of a similar diameter
      (60-100 A) irrespective of the precursor protein. Image processing has enhanced
      electron micrographs to show that amyloid fibrils appear to be composed of
      protofilaments wound around one another. In combination with other techniques,
      including X-ray fiber diffraction and solid state NMR, electron microscopy has
      revealed that the internal structure of the amyloid fibril is a ladder of beta
      sheet structure arranged in a cross-beta conformation.

PMID- 16103999
TI  - Amyloid-beta aggregates formed at polar-nonpolar interfaces differ from amyloid
      beta protofibrils produced in aqueous buffers.
AB  - The deposition of aggregated amyloid-beta (Abeta) peptides in the brain as senile
      plaques is a pathological hallmark of Alzheimer's disease (AD). Several lines of
      evidence indicate that fibrillar and, in particular, soluble aggregates of these
      40- and 42-residue peptides are important in the etiology of AD. Recent studies
      also stress that amyloid aggregates are polymorphic and that a single polypeptide
      can fold into multiple amyloid conformations. Here we review our recent reports
      that Abeta(1-40) in vitro can form soluble aggregates with predominant beta
      structures that differ in stability and morphology. One class of aggregates
      involved soluble Abeta protofibrils, prepared by vigorous overnight agitation of
      monomeric Abeta(1-40) in low ionic strength buffers. These aggregates were quite
      stable and disaggregated to only a limited extent on dilution. A second class of
      soluble Abeta aggregates was generated at polar-nonpolar interfaces. Aggregation
      in a two-phase system of buffer over chloroform occurred more rapidly than in
      buffer alone. In buffered 2% hexafluoroisopropanol (HFIP), microdroplets of HFIP
      were formed and the half-time for aggregation was less than 10 minutes. Like
      Abeta protofibrils, these interfacial aggregates showed increased thioflavin T
      fluorescence and were rich in beta-structure by circular dichroism. However,
      electron microscopy and atomic force microscopy revealed very different
      morphologies. The HFIP aggregates formed initial globular clusters that
      progressed over several days to soluble fibrous aggregates. When diluted out of
      HFIP these aggregates initially were very unstable and disaggregated completely
      within 2 minutes. However, their stability increased as they progressed to
      fibers. It is important to determine whether similar interfacial Abeta aggregates
      are produced in vivo.

PMID- 16104000
TI  - Molecular pathology and pathogenesis of inclusion-body myositis.
AB  - We summarize the molecular phenotype, diagnostic criteria, and the newest
      advances related to seeking the pathogenic mechanism(s) of sporadic inclusion
      body myositis (s-IBM), a muscle disease usually of persons over age 50. On the
      basis of our research, several processes seem to be important in relation to the
      still-speculative pathogenesis: 1) increased transcription and accumulation of
      amyloid-beta precursor protein (AbetaPP), and accumulation of its proteolytic
      fragment Abeta; 2) abnormal accumulation of cholesterol, caveolin-1, and
      apolipoprotein E; 3) oxidative stress; 4) accumulations of intramuscle fiber
      multiprotein aggregates; and 5) evidence that unfolded/misfolded proteins
      participate in s-IBM pathogenesis. Our basic hypothesis is that overexpression of
      AbetaPP within the aging muscle fibers is an early upstream event causing a
      subsequent pathogenic cascade.

PMID- 16104001
TI  - Characterization of paired helical filaments by scanning transmission electron
      microscopy.
AB  - Paired helical filaments (PHFs) are abnormal twisted filaments composed of
      hyperphosphorylated tau protein. They are found in Alzheimer's disease and other
      neurodegenerative disorders designated as tauopathies. They are a major component
      of intracellular inclusions known as neurofibrillary tangles (NFTs). The
      objective of this review is to summarize various structural studies of PHFs in
      which using scanning transmission electron microscopy (STEM) has been
      particularly informative. STEM provides shape and mass per unit length
      measurements important for studying ultrastructural aspects of filaments. These
      include quantitative comparisons between dispersed and aggregated populations of
      PHFs as well as comparative studies of PHFs in Alzheimer's disease and other
      neurodegenerative disorders. Other approaches are also discussed if relevant or
      complementary to studies using STEM, e.g., application of a novel staining
      reagent, Nanovan. Our understanding of the PHF structure and the development of
      PHFs into NFTs is presented from a historical perspective. Others goals are to
      describe the biochemical and ultrastructural complexity of authentic PHFs, to
      assess similarities between authentic and synthetic PHFs, and to discuss recent
      advances in PHF modeling.

PMID- 16104002
TI  - Structural insights into Alzheimer filament assembly pathways based on site
      directed mutagenesis and S-glutathionylation of three-repeat neuronal Tau
      protein.
AB  - Although Tau and MAP2 readily assemble into straight filaments (SFs), Tau's
      unique ability to form paired-helical filaments (PHFs) may offer clues as to why
      Tau's microtubule-binding region (MTBR) is the exclusive building block of the
      neurofibrillary tangles that accumulate during Alzheimer's disease. To learn more
      about the factors permitting Tau to form both SFs and PHFs, we investigated the
      microtubule binding, thiol oxidation, and polymerization reactions of the monomer
      and dimer forms of Tau and MAP2 MTBRs. This review focuses on electron
      microscopic evidence (1) that facilitated the identification of amino acid
      residues within 3-repeat Tau that promote PHF formation; and (2) provided
      experimental evidence for the polymerization of S-glutathionylated three-repeat
      Tau, a reaction that unambiguously demonstrates that disulfide-linked Tau-S-S-Tau
      dimer formation is not a compulsory step in filament assembly. We also consider
      these findings within the context of current views on the genetic and biochemical
      basis of Tau fibrillogenesis.

PMID- 16104003
TI  - Paired helical filaments (PHFs) are a family of single filament structures with a
      common helical turn period: negatively stained PHF imaged by TEM and measured
      before and after sonication, deglycosylation, and dephosphorylation.
AB  - Isolated paired helical filaments (PHFs) were visualized on glutaraldehyde vapor
      treated thin approximately 10-nm thick indirect carbon films using high
      resolution transmission electron microscopy (TEM) and the negative stain,
      phosphotungstate acid (PTA) at near neutral pH of 6.8. PHF preparations were
      prepared with and without 1 minute of sonication. These same PHF were also
      deglycosylated with endoglycosidase F/N-glycosidase F for 1 hour or the PHF were
      dephosphorylated with PP-2A for 1 hour. The negatively stained PHF filaments were
      quantitatively studied by measuring their wide regions (W) their thin regions (T)
      and their helical turn period (L) and these separate parameters were averaged for
      each filament. In the unsonicated PHF preparation there were PHF, cylindrical
      filaments with periodic thin regions (CF-PT), cylindrical filaments (CF), as well
      as 2.0-nm tau polymer-like filaments. The CF-PT were characterized by W, T, and L
      measurements and the CF were characterized by diameter measurements. The paired
      helical filament model proposed by Kidd (1963, Nature 197:192-193) of two
      approximately 10 nm filaments twisting around each other every approximately 80
      nm with a thin region of 10 nm and a wide region of 25 nm does not correspond to
      the PHF structures found. None of the PHF we observed were composed of a pair of
      filaments and all of the PHF appear to be a single filament. The wide regions
      ranged from 12.5-27 nm and the thin regions ranged from 4.5-12.3 nm. The helical
      turn periods ranged from 76-85 nm and were generally about 80 nm. Only the
      helical turn period of approximately 80 nm was a common property of the whole
      family of PHF structures. The CF-PT appear to be a PHF precursor filament.
      Deglycosylation of the PHF and CF-PT reduced their sizes by 0.5-0.6 nm and 0.7
      1.0 nm, respectively, and the right-hand helicity of the PHF was lost after
      deglycosylation. Dephosphorylation with PP-2A reduced the PHF wide regions by 6.0
      nm and the thin regions by 2.6 nm.

PMID- 16104004
TI  - Plasma zinc concentrations of mothers and the risk of nonsyndromic oral clefts in
      their children: a case-control study in the Philippines.
AB  - BACKGROUND: Findings from animal experiments suggest a link between poor maternal
      zinc status and increased risk of oral clefts in offspring; however, there are
      few human studies on this issue. METHODS: A case-control study was conducted
      using 74 case mothers of children with nonsyndromic cleft lip with or without
      cleft palate (CL/P, n=57) or cleft palate alone (CP, n=17), and 283 control
      mothers of unaffected children recruited in the Philippines in early 2003.
      Maternal zinc status was assessed by determining plasma zinc concentrations a
      mean of 5 years after delivery of the index child. Odds ratios (ORs) of estimates
      of the relative risk of oral clefts were calculated for quartiles of maternal
      plasma zinc concentrations. RESULTS: The mean plasma zinc concentration of CL/P
      case mothers (9.6+/-1.2, SD micromol/l) was significantly lower than that in
      control mothers (10.1+/-1.6 micromol/l; P<0.05). Low plasma zinc concentrations
      (<11.0 micromol/l) were found in 88% and 94% of CL/P and CP case mothers,
      respectively, and in 72% of controls (P<0.05). The ORs for CL/P and CP combined,
      adjusted for potential confounding factors, decreased with increasing quartile of
      plasma zinc as follows: 1.0 (lowest quartile reference), 0.83 (95% confidence
      interval 0.37-1.89), 0.70 (0.31-1.68), and 0.26 (0.10-0.70) (P trend=0.008).
      CONCLUSIONS: Low plasma zinc concentrations were common in Filipino women of
      reproductive age, and higher plasma zinc concentrations were associated with a
      lower risk for oral clefts in their children.

PMID- 16104005
TI  - Combined chemotherapy and teratogenicity.
AB  - BACKGROUND: The concomitant occurrence of breast cancer and pregnancy is
      relatively uncommon. We report the case of a patient with syndactyly, cleft
      hands, and absence of distal finger phalanges associated with maternal exposure
      to chemotherapeutic agents during the first trimester of pregnancy. These
      associations have not been previously described. CASE: The patient was born by
      normal delivery after 38 weeks of pregnancy. His mother became pregnant while
      receiving chemotherapy (cyclophosphamide, 5-fluorouracil, and adriamycin) for
      breast cancer, and the fetus was exposed to these drugs from conception to the
      16th week of pregnancy. At birth, anomalies were observed, including a high
      arched palate, microcephaly, a flat nasal bridge, bilateral syndactyly in the
      first and second fingers with a hand cleft between the second and third fingers
      and hypoplasia of the fifth fingers, and dystrophic nail of the fourth finger of
      the left hand. The patient's growth and development were deficient. CONCLUSIONS:
      The malformations associated with in utero exposure to these chemotherapeutic
      agents are highly variable, but growth deficiency and anomalies of the
      craniofacial region and limbs are the most common. The pattern of malformations
      in children who were congenitally exposed to chemotherapeutic agents appears to
      be directly related to the age at and duration of exposure, rather than to the
      specific drug itself. Effective contraception is essential for the safe use of a
      potential teratogen in nonpregnant women of reproductive age.

PMID- 16104007
TI  - Evaluation of the RF field uniformity of a double-tuned 31P/1H birdcage RF coil
      for spin-echo MRI/MRS of the diabetic foot.
AB  - PURPOSE: To evaluate the B1 field uniformity of a double-tuned birdcage coil
      designed for (31)P/(1)H MRI/MRS spin-echo (SE) imaging of the metatarsal head
      region of the foot in neuropathic diabetic patients. MATERIALS AND METHODS: A low
      pass double-tuned (31)P/(1)H RF birdcage coil was constructed to fit over the
      adult forefoot. Flip angle (FA) maps were created from B1 data acquired at the 3T
      (31)P (four normal subjects) and (1)H (five normal subjects) frequencies. T2
      weighted (T2-W) (1)H images, (31)P rapid acquisition with relaxation enhancement
      (RARE) images, and composite SE pulse CSI data were acquired to demonstrate the
      uniformity of the resulting images and data. RESULTS: The means and standard
      deviations (SDs) of the range of FAs across the feet of the volunteer subjects
      indicated good uniformity (the maximum coefficients of variation (CVs) for all of
      the (31)P and (1)H FA maps were 7.6% and 7.3%, respectively). The FA values
      across the metatarsal head region indicated a maximum signal intensity variation
      of +/-3% in a RARE image acquired using an echo train length of 32. CONCLUSION: A
      (31)P/(1)H birdcage coil constructed for MRI/MRS studies of the human forefoot
      provided sufficient signal uniformity of SE data to facilitate accurate (31)P
      concentration measurements in muscle.

PMID- 16104008
TI  - Magnetic resonance imaging artifacts caused by aneurysm clips and shunt valves:
      dependence on field strength (1.5 and 3 T) and imaging parameters.
AB  - PURPOSE: To evaluate artifact sizes at 3 T compared to at 1.5 T, and to evaluate
      the influence of scanning parameters with respect to artifact size on a 3-T
      magnetic resonance imaging (MRI) system. MATERIALS AND METHODS: Two aneurysm
      clips and five shunt valves were imaged in a water phantom at 1.5 and 3 T. At 3 T
      the influence of bandwidth (spin echo (SE) images) and echo time (gradient echo
      (GRE) images) on artifact size (area and extension in two orthogonal directions)
      was investigated. RESULTS: Artifact sizes increased substantially (typically 5-10
      mm) at 3 T, compared to at 1.5 T, for implants entirely made of metallic
      materials, whereas the increase was the size less prominent (0-5 mm) for implants
      only partly containing metal. Artifact areas could be altered by changing the
      bandwidth or the echo time to about the same extent as it was affected by the
      increased field strength. CONCLUSION: Artifact sizes increase at 3 T, compared to
      at 1.5 T, depending on the type and composition of the implant, but can be
      substantially reduced by altering the imaging parameters. Optimization of imaging
      protocols to minimize artifacts is therefore important at higher field strengths.

PMID- 16104009
TI  - The impact of partial-volume effects in dynamic susceptibility contrast magnetic
      resonance perfusion imaging.
AB  - PURPOSE: To demonstrate the degree of the cerebral blood flow (CBF) estimation
      bias that could arise from distortion of the arterial input function (AIF) as a
      result of partial-volume effects (PVEs) in dynamic susceptibility contrast (DSC)
      magnetic resonance imaging (MRI). MATERIALS AND METHODS: A model of the volume
      fraction an artery occupies in a voxel was devised, and a mathematical
      relationship between the amount of PVE and the measured baseline MR signal
      intensity was derived. Based on this model, simulation studies were performed to
      assess the impact of PVE on CBF. Furthermore, the effectiveness of linear PVE
      compensation approaches on the concentration function was investigated. RESULTS:
      Simulation results showed a nonlinear relationship between PVE and the resulting
      CBF measurement error. In addition to AIF underestimation, PVE also causes
      distortions of AIF frequency characteristics, leading to CBF errors varying with
      mean transit time (MTT). An uncorrected AIF measured at a voxel with a partial
      volume fraction of <or=50% could produce a CBF overestimation of more than
      fourfold. Linear compensation of the concentration curves did not produce correct
      CBF estimates. CONCLUSION: PVE can induce significant CBF estimation biases. In
      addition, the MTT dependence of CBF accuracy raises doubts of the validity of
      adopting a single cross-calibration factor (i.e., setting normal white matter to
      22 mL minute(-1) (100 g)(-1)) to obtain CBF values with absolute units. The
      impact of PVE may be reduced by decreasing the maximum arterial signal drop in
      the perfusion images. To correct the AIF distortions introduced by PVE, the
      nonlinear relationship between the impact of PVE on MR signal intensity and
      contrast concentration function must be considered.

PMID- 16104010
TI  - Functional magnetic resonance imaging activation detection: fuzzy cluster
      analysis in wavelet and multiwavelet domains.
AB  - PURPOSE: To present novel feature spaces, based on multiscale decompositions
      obtained by scalar wavelet and multiwavelet transforms, to remedy problems
      associated with high dimension of functional magnetic resonance imaging (fMRI)
      time series (when they are used directly in clustering algorithms) and their poor
      signal-to-noise ratio (SNR) that limits accurate classification of fMRI time
      series according to their activation contents. MATERIALS AND METHODS: Using
      randomization, the proposed method finds wavelet/multiwavelet coefficients that
      represent the activation content of fMRI time series and combines them to define
      new feature spaces. Using simulated and experimental fMRI data sets, the proposed
      feature spaces are compared to the cross-correlation (CC) feature space and their
      performances are evaluated. In these studies, the false positive detection rate
      is controlled using randomization. To compare different methods, several points
      of the receiver operating characteristics (ROC) curves, using simulated data, are
      estimated and compared. RESULTS: The proposed features suppress the effects of
      confounding signals and improve activation detection sensitivity. Experimental
      results show improved sensitivity and robustness of the proposed method compared
      to the conventional CC analysis. CONCLUSION: More accurate and sensitive
      activation detection can be achieved using the proposed feature spaces compared
      to CC feature space. Multiwavelet features show superior detection sensitivity
      compared to the scalar wavelet features.

PMID- 16104011
TI  - Three-dimensional contrast-enhanced steady-state free precession for improved
      catheter-directed coronary magnetic resonance angiography.
AB  - PURPOSE: To demonstrate the feasibility of three-dimensional thick-partition,
      contrast-enhanced, catheter-directed coronary artery magnetic resonance
      angiography (MRA) and test the hypothesis that three-dimensional imaging improves
      coronary artery background contrast-to-noise ratio (CNR) compared to two
      dimensional imaging. MATERIALS AND METHODS: Catheters were advanced into the
      coronary arteries of swine (N = 6) under MR guidance. Three-dimensional coronary
      MRA was performed after intracoronary injection of a small dose of contrast media
      using magnetization-prepared steady-state free precession (SSFP) with two thick
      partitions. For comparison, two magnetization-prepared two-dimensional SSFP scans
      were also performed, one with no signal averaging and one with two signal
      averages. All sequences had the same coverage and in-plane spatial resolution.
      RESULTS: The coronary artery was successfully catheterized in all (6/6) animals.
      CNR for three-dimensional imaging was 11.1 +/- 1.2 for proximal arterial segments
      and 4.3 +/- 0.4 for distal segments. Without averaging, two-dimensional imaging
      CNRs for proximal and distal segments were 5.0 +/- 0.7 and 1.2 +/- 0.2,
      respectively. With averaging, two-dimensional imaging CNRs for proximal and
      distal segments were 9.4 +/- 1.5 and 2.9 +/- 0.4, respectively. Three-dimensional
      imaging showed a statistically significant increase in CNR over all two
      dimensional imaging for both proximal and distal segments (P < 0.05). CONCLUSION:
      Three-dimensional thick-partition, contrast-enhanced, catheter-directed coronary
      MRA is feasible and improves CNR over two-dimensional projection imaging.

PMID- 16104012
TI  - No evidence for triallelic inheritance of MKKS/BBS loci in Amish Mckusick-Kaufman
      syndrome.
AB  - It has been hypothesized that two mutations in one gene are not sufficient and
      that three mutations between two genes are required for penetrance in some cases
      of Bardet-Biedl syndrome (the so-called "triallelic inheritance" model). McKusick
      Kaufman syndrome (MKS) is allelic to one form of Bardet-Biedl syndrome (BBS). We
      describe an Amish family with MKS, where three children were affected with
      homozygous MKKS (BBS6) mutations (H84Y and A242S on both alleles), their father
      was a carrier, and their mother was homozygous for the same MKKS mutations, but
      she was non-penetrant. Genotyping and/or sequencing of BBS1, BBS2, BBS3, BBS4,
      BBS5, BBS7, and BBS8 excluded "triallelic inheritance" for each gene either by an
      incompatible inheritance pattern or an absence of mutations in the coding region
      and the intronic splice junctions of these genes. We conclude that the
      "triallelic" model does not explain the incomplete penetrance of MKS.

PMID- 16104013
TI  - Cryptic duplication and deletion of 9q34.3 --> qter in a family with a
      t(9;22)(q34.3;p11.2).
AB  - A newborn male was referred for genetic evaluation because of multiple congenital
      abnormalities. Physical findings included a round face, telecanthus,
      hypertelorism, a short upturned nose with anteverted nares, small ears,
      micrognathia, short toes, and congenital heart disease. Chromosome analysis
      detected a possible deletion of 9qter because of satellite material on 9qter.
      Delineation by FISH and microarray CGH studies showed
      46,XY,der(9)t(9;22)(q34.3;p11.2). The mother and maternal grandfather had a
      balanced t(9;22)(q34.3;p11.2) rearrangement. Also, the maternal great-aunt of the
      propositus was found to have a duplication of 9q34.3 --> qter. FISH was required
      to delineate her karyotype, which was 46,XX.ish der(22)t(9;22)(q34.3;p11.2). This
      maternal great-aunt and one of her daughters (cytogenetics not done) have a
      relatively normal phenotype, only reporting mild learning disabilities in school.
      Since the 22p material involved in this rearrangement is clinically irrelevant,
      this report describes an individual with a pure deletion of 9q34.3 --> qter and
      another with a pure duplication of 9q34.3 --> qter.

PMID- 16104014
TI  - Detection of acute renal ischemia in swine using blood oxygen level-dependent
      magnetic resonance imaging.
AB  - PURPOSE: To determine the feasibility and sensitivity of blood oxygen level
      dependent (BOLD) magnetic resonance imaging (MRI) to detect acute renal ischemia,
      using a swine model, and to present the causes of variability and assess
      techniques that minimize variability introduced during data analysis. MATERIALS
      AND METHODS: BOLD MRI was performed in axial and coronal planes of the kidneys of
      five swine. Color R2* maps were calculated and mean R2* values and 95% confidence
      intervals (CIs) for the cortex and medulla were determined for baseline, renal
      artery occlusion and reperfusion conditions. Paired Student's t-tests were used
      to determine significance. RESULTS: Mean R2* measurements increased from baseline
      during renal artery occlusion in the cortex (axial, 13.8-24.6 second(-1);
      coronal, 14.4-24.7 second(-1)) and medulla (axial, 19.3-32.2 second(-1); coronal,
      20.1-30.7 second(-1)). These differences were significant for both the cortex
      (axial, P < 0.04; coronal, P < 0.005) and medulla (axial, P < 0.02; coronal, P <
      0.0005). No significant change was observed in the contralateral kidney.
      CONCLUSION: R2* values were significantly higher than baseline for medulla and
      cortex during renal artery occlusion. More variability exists in R2* measurements
      in the medulla than the cortex and in the axial than the coronal plane.

PMID- 16104015
TI  - Common binding site for disialyllactose and tri-peptide in C-fragment of tetanus
      neurotoxin.
AB  - Clostridial neurotoxins are comprised of botulinum (BoNT) and tetanus (TeNT),
      which share significant structural and functional similarity. Crystal structures
      of the binding domain of TeNT complexed with disialyllactose (DiSia) and a tri
      peptide Tyr-Glu-Trp (YEW) have been determined to 2.3 and 2.2 A, respectively.
      Both DiSia and YEW bind in a shallow cleft region on the surface of the molecule
      in the beta-trefoil domain, interacting with a set of common residues, Asp1147,
      Asp1214, Asn1216, and Arg1226. DiSia and YEW binding at the same site in tetanus
      toxin provides a putative site that could be occupied either by a ganglioside
      moiety or a peptide. Soaking experiments with a mixture of YEW and DiSia show
      that YEW competes with DiSia, suggesting that YEW can be used to block
      ganglioside binding. A comparison with the TeNT binding domain in complex with
      small molecules, BoNT/A and /B, provides insight into the different modes of
      ganglioside binding.

PMID- 16104016
TI  - Alpha-alpha linking motifs and interhelical orientations.
AB  - While the geometry and sequence preferences of turns that link two beta-strands
      have been exhaustively explored, the corresponding preferences for sequences that
      link helical structures have been less well studied. Here we examine the
      interhelical geometry of two connected helices as a function of their link's
      length. The interhelical geometry of a helical pair appears to be significantly
      influenced by the number of linking residues. Furthermore, for relatively short
      link lengths, a very limited number of predominant conformations are observed,
      which can be categorized by their phi/psi angles. No more than two predominant
      linking backbone conformations are observed for a given link length, and some
      linking backbone conformations correlate strongly with distinctive interhelical
      geometric parameters. In this study, sequence and hydrogen-bonding patterns were
      defined for predominant interhelical link motifs. These results should assist in
      both protein structure prediction and de novo protein design.

PMID- 16104017
TI  - Structures of vertebrate hyaluronidases and their unique enzymatic mechanism of
      hydrolysis.
AB  - Human hyaluronidases (Hyals) are a group of five endo-beta-acetyl-hexosaminidase
      enzymes, Hyal-1, -2, -3, -4, and PH-20, which degrade hyaluronan using a
      hydrolytic mechanism of action. Catalysis by these Hyals has been shown to follow
      a double-displacement scheme. This involves a single Glu residue within the
      enzyme, the only catalytic residue, as the proton donor (acid). Also involved is
      a carbonyl group of the hyaluronan (HA) N-acetyl-D-glucosamine as a unique type
      of nucleophile. Thus the substrate participates in the mechanism of action of its
      own catalysis. An oxocarbonium ion transition state is postulated, but there is
      no formation of a covalent enzyme-glycan intermediate, as found in most such
      reactions. The major domain is catalytic and has a distorted (beta/alpha)8 triose
      phosphate isomerase (TIM) barrel fold. The C-terminal domain is separated by a
      peptide linker. Each Hyal has a different C-terminal sequence and structure, the
      function of which is unknown. These unique C-termini may participate in the
      additional function(s) associated with these multifunctional enzymes.

PMID- 16104018
TI  - Crystal structure of the global regulatory protein CsrA from Pseudomonas putida
      at 2.05 A resolution reveals a new fold.

PMID- 16104019
TI  - Crystal structure of a putative modulator of DNA gyrase (pmbA) from Thermotoga
      maritima at 1.95 A resolution reveals a new fold.

PMID- 16104020
TI  - Statistical analysis of predominantly transient protein-protein interfaces.
AB  - A non-redundant set of 170 protein-protein interfaces of known structure was
      statistically analyzed for residue and secondary-structure compositions, pairing
      preferences and side-chain-backbone interaction frequencies. By focussing mainly
      on transient protein-protein interfaces, the results underline previous findings
      for protein-protein interfaces but also show some new interesting aspects of
      transient interfaces. The residue compositions at interfaces found in this study
      correlate well with the results of other studies. On average, contacts between
      pairs of hydrophobic and polar residues were unfavorable, and the charged
      residues tended to pair subject to charge complementarity. Secondary structure
      composition analysis shows that neither helices nor beta-sheets are dominantly
      populated at interfaces. Analyzing the pairing preferences of the secondary
      structure elements revealed a higher affinity within the same elements and
      alludes to tight packings. In addition, the results for the side-chain and
      backbone interaction frequencies, which were measured under more stringent
      conditions, showed a high occurrence of side-chain-backbone interactions. Taking
      a closer look at the helix and beta-sheet binding frequencies for a given side
      chain and backbone interaction underlined the relevance of tight packings. The
      polarity of interfaces increased with decreasing interface size. These types of
      information may be useful for scoring complexes in protein-protein docking
      studies or for prediction of protein-protein interfaces from the sequences alone.

PMID- 16104021
TI  - Does secondary structure determine tertiary structure in proteins?
AB  - Is highly approximate knowledge of a protein's backbone structure sufficient to
      successfully identify its family, superfamily, and tertiary fold? To explore this
      question, backbone dihedral angles were extracted from the known three
      dimensional structure of 2,439 proteins and mapped into 36 labeled, 60 degrees x
      60 degrees bins, called mesostates. Using this coarse-grained mapping, protein
      conformation can be approximated by a linear sequence of mesostates. These linear
      strings can then be aligned and assessed by conventional sequence-comparison
      methods. We report that the mesostate sequence is sufficient to recognize a
      protein's family, superfamily, and fold with good fidelity.

PMID- 16104022
TI  - Structural and functional characterization of a 5,10-methenyltetrahydrofolate
      synthetase from Mycoplasma pneumoniae (GI: 13508087).
AB  - Mycoplasma pneumoniae 5,10-methenyltetrahydrofolate synthetase [MTHFS; also known
      as 5-formyltetrahydrofolate cycloligase; Enzyme Commission (EC) 6.3.3.2] belongs
      to a large cycloligase protein family with 97 sequence homologues from bacteria
      to human. To help define the molecular (biochemical and biophysical) function of
      the M. pneumoniae MTHFS, we have previously determined its crystal structure at
      2.2 A resolution (Chen et al., Proteins 2004;56:839-843). In this current study,
      activity assays confirmed the functionality of the recombinant protein, with K(m)
      = 165 microM for 5-formyltetrahydrofolate (5-FTHF) and K(m) = 166 microM for
      MgATP. The methenyltetrahydrofolate activity of M. pneumoniae MTHFS has a
      requirement for divalent metal ions with Mg2+ being most effective, and an
      absolute requirement for nucleoside 5'-triphosphates with adenosine triphosphate
      (ATP) being most effective. Crystallization in the presence of substrates (MgATP,
      with or without 5-FTHF) produced the complex structures of the protein with
      adenosine diphosphate (ADP) and phosphate at 2.2 A resolution; with ADP,
      phosphate, and 5-FTHF at 2.5 A resolution. These structures directly demonstrated
      that the role of Mg2+ in the reaction is to form the ATP--Mg2+-enzyme complex.

PMID- 16104023
TI  - Retrospective motion compensation using variable-density spiral trajectories.
AB  - PURPOSE: To develop a method of retrospectively correcting for motion artifacts
      using a variable-density spiral (VDS) trajectory. MATERIALS AND METHODS: Each VDS
      interleaf was designed to adequately sample the same center region of k-space.
      This central overlapping region can then be used to measure rigid body motion
      between the acquisition of each VDS interleaf. By applying appropriate phase
      shifts and rotations of the k-space data, rigid body motion artifacts can be
      removed, resulting in images with less motion corruption. RESULTS: Both phantom
      and volunteer experiments are shown, demonstrating the technique's ability to
      further reduce artifacts in images acquired with an already motion-resistant
      acquisition trajectory. Registration accuracy is highly dependent on the
      trajectory design parameters. This space was explored to find an optimal design
      of VDS trajectories for motion compensation. CONCLUSION: Using appropriately
      designed VDS trajectories, residual motion artifacts can be significantly reduced
      by retrospectively correcting for in-plane rigid body motion. An overlapping
      region of approximately 8% of the central region of k-space and approximately 70
      interleaves were found to be near-optimal parameters for retrospective correction
      using VDS trajectories.

PMID- 16104024
TI  - The potential of angiogenesis soluble markers in chronic hepatitis C.
AB  - Angiogenesis, the formation of new vessels, has been reported to play a
      significant pathogenic role in liver damage-associated hepatitis C virus
      infection. Most of our current knowledge derives from immunohistochemical studies
      of hepatic biopsy samples obtained from chronic hepatitis C (CHC) patients. We
      evaluated whether CHC is associated with elevated serum levels of angiogenesis
      markers and whether these are modulated by therapy. Vascular endothelial growth
      factor (VEGF), angiopoietin-2 (Ang-2), and soluble Tie-2 (sTie-2) were determined
      in the serum of 36 CHC patients, before and after receiving antiviral combination
      therapy with pegylated interferon alpha-2b plus ribavirin, and in 15 healthy
      controls. CHC patients showed elevated baseline VEGF and Ang-2 levels. After
      treatment, both factors were decreased, whereas antiangiogenic sTie-2 was
      increased, indicating a shift toward an "anti-angiogenic" profile of serum
      markers in CHC patients. In conclusion, this suggests that serum VEGF, Ang-2, and
      sTie-2 levels could be useful as noninvasive, mechanistically based markers of
      response to therapy and disease progression in CHC.

PMID- 16104025
TI  - Time-resolved fluorescent chirality sensing and imaging of malate in aqueous
      solution.
AB  - Chiral discrimination of malates in aqueous solutions at near-neutral pH is
      achieved through fluorescence measurement and imaging using the europium
      tetracycline complex (EuTc) as a fluorescent probe. The method is based on the
      significantly different fluorescence properties of the ternary complexes (Eu-Tc
      malate) formed between EuTc and the enantiomeric malates. The enantiomeric excess
      (ee) of chiral malates can be quantified by both steady-state and time-resolved
      fluorescence, using either a conventional fluorescence microplate reader or
      fluorescence imaging. It offers a facile and sensitive method for high-throughput
      chiral discrimination.

PMID- 16104026
TI  - An eutomer/distomer ratio near unity does not justify non-enantiospecific assay
      methods in bioequivalence studies.
AB  - The aim of the present investigation was to compare the pharmacokinetics of two
      tablet formulations of 600 mg of racemic ibuprofen obtained using enantiospecific
      and non-enantiospecific assays, in order to explore if chiral assays should be
      employed in bioequivalence studies of chiral active substances. The
      stereoselective assay showed that, for both formulations, there was an initial
      phase where (R)-ibuprofen was the predominant enantiomer followed by a final
      phase where (S)-ibuprofen was the predominant one. Results from both analytical
      methods proved that the two formulations were bioequivalent. However, the chiral
      bioanalytical method detected a larger difference in the eutomer than that showed
      by the nonchiral bioanalytical method. In conclusion, although the exposure
      ratios of enantiomers are near unity, the measurement of unresolved ibuprofen
      alone is not an adequate measure of bioequivalence since it may mask the actual
      difference in the eutomer exposure among formulations.

PMID- 16104027
TI  - Chiral aminonaphthol-catalyzed enantioselective carbonyl addition of diethylzinc
      to aromatic aldehydes high-throughput screened by CD-HPLC analysis.
AB  - Optically active aminonaphthols derivatives are obtained by condensation of 2
      naphthol, substituted benzaldehyde, and (S)-methylbenzylamine under mild
      conditions, without side products. Their absolute configurations are determined
      by X-ray crystallographic analysis. The addition of diethylzinc to aromatic
      aldehydes is considerably accelerated by the presence of a catalytic amount of
      crystalline to give, after hydrolysis, the corresponding 1-phenylpropanol in good
      enantiomeric purity, as determined by CD-HPLC analysis as HTPS (high-throughput
      screening).

PMID- 16104028
TI  - Clinical outcome of patients with lymph node-negative breast carcinoma who have
      sentinel lymph node micrometastases detected by immunohistochemistry.

PMID- 16104030
TI  - Social organization of the Milne-Edward's potto.
AB  - Nocturnal prosimian primates are often seen alone during their nocturnal
      activities, and are therefore categorized as "solitary". Recent research has
      shown that these animals actually possess social networks that differ among
      species. Here we present new information on one of the lesser studied prosimian
      primates, the potto, derived from fieldwork in Cameroon that employed
      radiotelemetry and behavioral observations. An analysis of association patterns
      and home-range overlaps between animals revealed that pottos associated more
      frequently with conspecifics than expected for a supposedly solitary primate.
      Certain males and females that were seen together regularly throughout the study,
      but were not observed to have contact with other pottos of the opposite sex, were
      labeled as "pairs". These pairs were found to have higher levels of association
      with each other than with other conspecifics. The only affiliative and sexual
      behaviors observed between members of the opposite sex occurred within the pairs
      of pottos. Although given the secretive nature of these primates, the possibility
      of extrapair copulations cannot be ruled out, their relatively small testis size
      indicates that sperm competition is not so important for this species.

PMID- 16104031
TI  - Patterns of male residency and intergroup transfer in gray-cheeked mangabeys
      (Lophocebus albigena).
AB  - We describe the movements and fates of 36 collared gray-cheeked male mangabeys
      (Lophocebus albigena) that resided in seven social groups in Kibale National
      Park, Uganda. The male mangabeys were captured, radiotagged, and then contacted
      regularly over a period of up to 8 years. Individuals varied considerably in how
      tightly they were associated with their groups. "Central" males were usually
      found in close spatial association with their own groups, but they sometimes
      visited others. "Peripheral" males were often found several hundred meters away
      from their own groups. Most adult males were characterized by repeated intergroup
      transfers, manifested as "visits" and "dispersals." Visits were transfers that
      did not result in mating. The visits were brief, and ranged from a few minutes to
      a few days before the male returned to his previous group, moved on to another
      group, or returned to solitary life. The term "dispersal" refers to a transfer
      that results in mating, after which the male remains in the new group. Young
      males began to drift away from their natal groups in early subadulthood, but the
      timing of first associations with estrous females in other groups was highly
      variable. Natal dispersers were generally solitary for a month or more, and at
      least half moved into nonadjacent groups. Secondary dispersal was common. After
      they immigrated, adult males remained in a group for a median of 19 months before
      they emigrated again, with the probability of departure being approximately
      constant in time. Secondary dispersal was usually made into an adjacent group and
      lasted less than 7 days. Emigration and immigration were not seasonal, and males
      emigrated singly and apparently independently; however, immigrations were clumped
      in time, and male dispersal contributed to considerable heterogeneity of group
      composition. L. albigena dispersal patterns are intermediate between those
      described for Papio baboons and forest Cercopithecus, and models that predict
      demographic consequences of dispersal for baboons can be refined to apply to
      mangabeys.

PMID- 16104032
TI  - Leaping behavior of Pithecia pithecia and Chiropotes satanas in eastern
      Venezuela.
AB  - I observed leaping behavior in the white-faced saki (Pithecia pithecia) and the
      black-bearded saki (Chiropotes satanas satanas) for 15 and 10 months,
      respectively, as part of a larger study of positional behavior in the tribe
      Pitheciini. I used focal animal instantaneous sampling to observe the two species
      on separate islands in their natural habitat at Guri Lake, Venezuela. Leaping
      behavior correlates with patterns of forest use and body size, and differences
      between the species relate more to habitat preferences than to habitat
      differences per se. Pithecia usually chose vertical or highly angled supports of
      lower tree portions for take-off and landing, and took off from a stationary
      posture. Chiropotes took off from the main crown or terminal branches, gaining
      momentum from locomotor movement before performing a leaping take-off. Pithecia's
      vertical body orientation and longer leap distance allowed it to assume a mid
      flight tuck to prepare for a hindlimb-first landing onto a solid support, and to
      absorb landing forces with its relatively longer hindlimbs. Chiropotes remained
      more pronograde throughout its leaps, and minimized landing forces by landing on
      all four limbs onto numerous flexible supports in the terminal branches. The
      smaller-bodied P. pithecia is specialized for vertical clinging and leaping, and
      exhibits behavioral and morphological parallels with other vertical clingers and
      leapers. The larger C. satanas is a generalized leaper that lacks morphological
      specializations for leaping. Pithecia's use of solid supports in the lower tree
      portions allows it to move quietly through the forest-one of a suite of behaviors
      related to predator avoidance. This example of variation within one behavioral
      category has implications for devising locomotor classifications and interpreting
      fossil remains.

PMID- 16104034
TI  - Flow cytometric sorting of fresh and frozen-thawed spermatozoa in the western
      lowland gorilla (Gorilla gorilla gorilla).
AB  - We adapted flow cytometry technology for high-purity sorting of X chromosome
      bearing spermatozoa in the western lowland gorilla (Gorilla gorilla gorilla). Our
      objectives were to develop methodologies for liquid storage of semen prior to
      sorting, sorting of liquid-stored and frozen-thawed spermatozoa, and assessment
      of sorting accuracy. In study 1, the in vitro sperm characteristics of gorilla
      ejaculates from one male were unchanged (P > 0.05) after 8 hr of liquid storage
      at 15 degrees C in a non-egg yolk diluent (HEPES-buffered modified Tyrode's
      medium). In study 2, we examined the efficacy of sorting fresh and frozen-thawed
      spermatozoa using human spermatozoa as a model for gorilla spermatozoa.
      Ejaculates from one male were split into fresh and frozen aliquots. X-enriched
      samples derived from both fresh and frozen-thawed human semen were of high
      purity, as determined by fluorescence in situ hybridization (FISH; 90.7%+/-2.3%,
      overall), and contained a high proportion of morphologically normal spermatozoa
      (86.0%+/-1.0%, overall). In study 3, we processed liquid-stored semen from two
      gorillas for sorting using a modification of methods for human spermatozoa. The
      sort rate for enrichment of X-bearing spermatozoa was 7.3+/-2.5 spermatozoa per
      second. The X-enriched samples were of high purity (single-sperm PCR: 83.7%) and
      normal morphology (79.0%+/-3.9%). In study 4 we examined frozen-thawed gorilla
      semen, and the sort rate (8.3+/-2.9 X-bearing sperm/sec), purity (89.7%), and
      normal morphology (81.4%+/-3.4%) were comparable to those of liquid-stored semen.
      Depending on the male and the type of sample used (fresh or frozen-thawed), 0.8
      2.2% of gorilla spermatozoa in the processed ejaculate were present in the X
      enriched sample. These results demonstrate that fresh or frozen-thawed gorilla
      spermatozoa can be flow cytometrically sorted into samples enriched for X-bearing
      spermatozoa.

PMID- 16104035
TI  - Patterns of anogenital swelling size and their endocrine correlates during
      ovulatory cycles and early pregnancy in free-ranging barbary macaques (Macaca
      sylvanus) of Gibraltar.
AB  - In macaques and other cercopithecoid primates, large anogenital swellings (AS)
      are generally found only in those species in which reproduction is not seasonally
      restricted. In this respect, the Barbary macaque is unusual because while it
      shows a marked degree of reproductive seasonality, it also exhibits a striking,
      exaggerated swelling of the circumanal region and labia. Information on the
      characteristics of AS in female Barbary macaques is limited in that it is largely
      based on semiquantitative assessments of swelling size, and there are no data on
      endocrine parameters associated with AS during ovulatory cycles or early
      pregnancy. In the present study, we combined quantitative measurements of four
      swelling size parameters (AS width, height, and depth, and labial width) using a
      video-imaging technique with fecal estrogen and progestagen determinations in
      free-ranging females of the Gibraltar Barbary macaque population to 1)
      characterize the pattern of AS throughout the mating season and early gestation,
      and 2) examine the relationships among changes in swelling size and endocrine
      parameters. The patterns of all four swelling parameters correlated significantly
      with one another, although measures of AS depth and labial width were difficult
      to obtain. Using the product of AS height and width, the data demonstrate that
      the occurrence of AS is highly seasonal, with pronounced cyclical changes during
      the mating season and early pregnancy. Furthermore, the swelling cycles are
      characterized by progressive size increases from the early to the late follicular
      phase, in association with an elevated estrogen:progestagen (E:P) ratio, with
      ovulation occurring during the maximum swelling phase. The results also
      demonstrated a conspicuous postconception increase in swelling between days 18-30
      of gestation. The postconception swellings were on average 80% of the size of
      that of the conception cycles, and were preceded by a large increase in fecal
      estrogen levels and the E:P ratio. This is the first study to characterize
      swelling patterns and their endocrine correlates during ovarian cycles and early
      pregnancy in naturally reproducing female Barbary macaques. The data provide a
      solid basis for further studies to explore sociosexual behavioral patterns and
      the functional significance of AS in this species.

PMID- 16104036
TI  - Chemotherapy with rituximab followed by high-dose therapy and autologous stem
      cell transplantation in patients with mantle cell lymphoma.
AB  - BACKGROUND: The authors evaluated the efficacy of chemotherapy combined with
      rituximab followed by high-dose therapy (HDT) plus autologous stem cell
      transplantation in patients with mantle cell lymphoma (MCL). METHODS: This was a
      retrospective analysis of 34 patients who were treated in 2 departments of
      hematology, including 29 patients (85%) who received first-line treatment.
      Rituximab was administered as 4 injections just before harvest in 25 patients
      (73%) or simultaneously with chemotherapy in 9 patients (27%). HDT included total
      body irradiation in 26 patients (77%). RESULTS: After induction therapy, all
      patients except one reached a response: There were 14 (41%) complete responses
      (CR) and 19 (56%) partial responses (PR). Stem cell harvest was successful in all
      patients but 2, with a median number of 5.9 CD34-positive cells per 10(6)/kg.
      Three months after transplantation, 24 patients (71%) were in CR, and 7 patients
      (21%) were in PR. At 3 years from the day of transplantation, the estimated
      overall survival was 87%. With a median follow-up at 2.6 years, the estimated
      median time to disease progression was 3.4 years. Rituximab treatment before
      harvest did not delay hematopoietic reconstitution: The median time it took
      patients to recover absolute neutrophil count to > 0.5 G/L was 10 days.
      CONCLUSIONS: Chemotherapy combined with rituximab followed by HDT improved the
      overall survival and progression-free survival in patients MCL without adding
      toxicities.

PMID- 16104037
TI  - Consumption of vegetables and fruits and risk of ovarian carcinoma.
AB  - BACKGROUND: To the authors' knowledge, only a few prospective studies to date
      have investigated the correlation between vegetable and fruit consumption and the
      risk of ovarian carcinoma and their results have been inconclusive. METHODS:
      Vegetable and fruit intake was assessed in relation to ovarian carcinoma, among
      62,573 postmenopausal women participating in The Netherlands Cohort Study on Diet
      and Cancer. Women reported on dietary habits and on other risk factors for cancer
      in a self-administered questionnaire in 1986. Follow-up of cancer was implemented
      by annual record linkage with The Netherlands Cancer Registry and a pathology
      register. After 11.3 years of follow-up, data regarding 252 incident invasive
      epithelial ovarian carcinoma cases and of 2216 subcohort members were available
      for case-cohort analyses. RESULTS: Multivariable-adjusted rate ratios (RR) of
      ovarian carcinoma for women in the highest compared with the lowest quintile of
      intake (RR(Q5 vs. Q1)) were 0.98 (95% confidence interval [95% CI], 0.61-1.58)
      for total vegetables and 1.11 (95% CI, 0.70-1.78) for total fruit. The RR(Q5 vs.
      Q1) values of ovarian carcinoma with intake of cooked vegetables, raw vegetables,
      brassicas, legumes, cooked leafy vegetables, and raw leafy vegetables were 1.35
      (95% CI, 0.83-2.21), 0.75 (95% CI, 0.48-1.18), 1.42 (95% CI, 0.88-2.29), 0.93
      (95% CI, 0.60-1.44), 1.05 (95% CI, 0.66-1.67), and 1.23 (95% CI, 0.75-2.02),
      respectively. With the exception of raw endive (multivariable-adjusted RR, 0.24;
      95% CI, 0.07-0.78), none of the individual vegetable or fruit items showed a
      statistically significant association with ovarian carcinoma. CONCLUSIONS: The
      results of the current study did not support a significant association between
      vegetable or fruit consumption and ovarian carcinoma risk in a cohort of
      postmenopausal women.

PMID- 16104038
TI  - Incidence and risk factors for the occurrence of non-AIDS-defining cancers among
      human immunodeficiency virus-infected individuals.
AB  - BACKGROUND: The objective of this study was to determine the rates and predictors
      of non-AIDS-defining cancers (NADCs) among a cohort of human immunodeficiency
      virus (HIV)-infected individuals. METHODS: The authors conducted a retrospective
      study of 4144 HIV-infected individuals who had 26,916 person-years of follow-up
      and who had open access to medical care at 1 of the United States military HIV
      clinics during the years 1988-2003. Cancer incidence rates were race specific and
      were adjusted for age; these were compared with national rates using logistic
      regression to assess predictors of NADC development. RESULTS: One hundred thirty
      three NADCs were diagnosed with a rate of 980 diagnoses per 100,000 person-years.
      The most frequent NADCs were skin carcinomas (basal cell and squamous cell),
      Hodgkin disease, and anal carcinoma. The results showed that there were higher
      rates of melanoma, basal and squamous cell skin carcinomas, anal carcinoma,
      prostate carcinoma, and Hodgkin disease among the HIV-infected cohort compared
      with age-adjusted rates for the general United States population. Predictors of
      NADCs included age older than 40 years (odds ratio [OR], 12.2; P < 0.001),
      Caucasian/non-Hispanic race (OR, 2.1; P < 0.001), longer duration of HIV
      infection (OR, 1.2; P < 0.001), and a history of opportunistic infection (OR,
      2.5; P < 0.001). The use of highly active antiretroviral therapy (HAART) was
      associated with lower rates of NADCs (OR, 0.21; P < 0.001). A low CD4 nadir or
      CD4 count at diagnosis (< 200 cells/mL) was not predictive of NADCs. CONCLUSIONS:
      The most frequent NADCs were primary skin malignancies. Melanoma, basal and
      squamous cell skin carcinomas, anal carcinoma, prostate carcinoma, and Hodgkin
      disease occurred at higher rates among HIV-infected individuals. The
      implementation of screening programs for these malignancies should be considered.
      Most risk factors for the development of NADCs are nonmodifiable; however, the
      use of HAART appeared to be beneficial in protecting against the development of
      malignant disease.

PMID- 16104039
TI  - Efficacy and tolerability of aprepitant for the prevention of chemotherapy
      induced nausea and emesis over multiple cycles of moderately emetogenic
      chemotherapy.
AB  - BACKGROUND: An aprepitant (APR) regimen was evaluated for prevention of nausea
      and emesis due to moderately emetogenic chemotherapy (MEC) over multiple cycles.
      METHODS: The authors performed a randomized, double-blind study. Eligible
      patients with breast carcinoma were naive to emetogenic chemotherapy and treated
      with cyclophosphamide alone or with doxorubicin or epirubicin. Patients were
      randomized to receive either an APR regimen (Day 1: APR 125 mg, ondansetron [OND]
      8 mg, and dexamethasone [DEX] 12 mg before chemotherapy and OND 8 mg 8 hrs later;
      Days 2-3: APR 80 mg every day) or a control regimen (Day 1: OND 8 mg and DEX 20
      mg before chemotherapy and OND 8 mg 8 hrs later; Days 2-3: OND 8 mg twice per
      day). Data on nausea, emesis, and use of rescue medication were collected. The
      primary end point was the proportion of patients with a complete response (CR; no
      emesis or use of rescue therapy) in Cycle 1. Efficacy end points for the multiple
      cycle extension were the probabilities of a CR in Cycles 2-4 and a sustained CR
      rate across multiple cycles. RESULTS: Of 866 patients randomized, 744 (85.9%)
      entered the multiple-cycle extension, and 650 (75.1%) completed all 4 cycles.
      Overall, the CR was greater with the APR regimen over the 4 cycles: 53.8% versus
      39.4% for Cycle 2, 54.1% versus 39.3% for Cycle 3, and 55.0% versus 38.4% for
      Cycle 4. The cumulative percentage of patients with a sustained CR over all 4
      cycles was greater with the APR regimen (P = 0.017). CONCLUSIONS: The APR regimen
      was more effective than a control regimen for the prevention of nausea and emesis
      induced by MEC over multiple chemotherapy cycles.

PMID- 16104040
TI  - Prognostic diversity among cytogenetic abnormalities in myelofibrosis with
      myeloid metaplasia.
AB  - BACKGROUND: Approximately 30-50% of patients with myelofibrosis with myeloid
      metaplasia (MMM) demonstrate detectable cytogenetic abnormalities, the prognostic
      value of which has not been completely defined by previous retrospective studies.
      The current prospective study addresses this issue in the context of currently
      accepted independent prognostic variables. METHODS: The current study is a single
      institution study in which patients with MMM were accrued between January 2000
      and August 2001 and followed in a prospective fashion. All study patients
      underwent bone marrow examination with cytogenetic studies as well as
      comprehensive clinical and laboratory evaluation at the time of karyotype
      analysis. RESULTS: Among the study cohort of 81 patients (with a median age of 61
      years; 54 males), the cytogenetic findings were normal in 44 patients (54%; Group
      1). The remaining 37 patients (46%) demonstrated either interstitial deletions
      involving the long arm of chromosome 13 or 20 (9 patients; Group 2) or other
      abnormalities (28 patients; Group 3). All study patients were followed
      prospectively for a minimum of 40 months (range, 40-55 months). Survival from the
      time of karyotypic analysis was found to be similar between Groups 1 and 2 but
      was significantly worse in Group 3. Furthermore, none of the patients in Group 2
      experienced leukemic transformation, whereas five patients each from the other
      two groups did. Multivariate analysis identified an unfavorable cytogenetic
      profile (Group 3), > or = 1% circulating blasts, a hemoglobin level of <10 g/dL,
      and constitutional symptoms as adverse prognostic features for overall survival.
      CONCLUSIONS: Specific cytogenetic lesions in patients with MMM might carry an
      independent prognostic effect for both survival and the risk of leukemic
      transformation. Such information should assist in decision making when
      considering aggressive treatment approaches.

PMID- 16104041
TI  - Hepatocyte paraffin 1 immunoexpression in esophageal brush samples.

PMID- 16104043
TI  - Telomerase activity in "suspicious" thyroid cytology.
AB  - BACKGROUND: Telomerase activity (TA) has been detected in most malignant
      neoplasms, including thyroid carcinomas. The authors studied the utility of TA
      detection as an ancillary tool to thyroid fine-needle aspiration (FNA) for
      patients with nonconclusive cytologic diagnoses. METHODS: Material obtained by
      FNA from palpable thyroid nodules in 167 consecutive patients was processed for
      conventional cytologic studies and simultaneously for TA study. Another 8
      patients were excluded from TA because of the presence of lymphocytes. All
      patients with negative results cases were followed for > 1 year, and those who
      had tumors that were suspicious or positive by FNA or TA underwent resection for
      pathologic study of nodules. TA was analyzed by telomere repeat amplification
      protocol-polymerase chain reaction analysis. RESULTS: After excluding 20 patients
      because of insufficient material for cytologic study, 120 patients had negative
      results for malignant cells in cytology material, and the remaining 27 patients
      had results that were either suspicious (n = 21 patients) or positive (n = 6
      patients). Histopathologic confirmation was obtained in 23 patients, including 18
      with suspicious cytology (1 with scanty material) and 5 with positive FNA. The
      histopathologic diagnoses were nodular hyperplasia in 5 patients, follicular
      adenoma in 3 patients, papillary carcinoma in 11 patients, follicular carcinoma
      in 1 patient, medullary carcinoma in 2 patients, and lymphoma in 1 patient. TA
      was detected in 6 of 18 histologically confirmed thyroid neoplasms (1 of 3
      follicular adenomas, 3 of 11 papillary carcinomas, 0 of 1 follicular carcinoma, 1
      of 2 medullary carcinomas, and 1 of 1 lymphoma), including 1 neoplasm with scanty
      atypical cells. CONCLUSIONS: The detection of TA helped to confirm neoplasia in 6
      of 23 suspicious thyroid nodules. Although it was less sensitive than FNA, TA
      specificity was 100% for neoplasia and 87.5% for malignancy. The sensitivity of
      thyroid FNA increased with the use of TA detection when cytology was
      nonconclusive for malignancy.

PMID- 16104044
TI  - Should women with atypical squamous cells, cannot exclude high-grade squamous
      intraepithelial lesion, receive reflex human papillomavirus-DNA testing?
AB  - BACKGROUND: The 2001 American Society for Colposcopy and Cervical Pathology
      Consensus Guidelines recommend that women who have Papanicolaou (Pap) smears
      diagnosed as atypical squamous cells (ASC), cannot exclude high-grade squamous
      intraepithelial lesion (HSIL) (ASC-H) should be referred for immediate
      colposcopic examination. The objective of this pilot study was to evaluate
      whether reflex human papillomavirus (HPV)-DNA testing performed on smears
      diagnosed as ASC-H may obviate the need for immediate colposcopic examination.
      METHODS: All ThinPrep Pap smears that were diagnosed as ASC-H or atypical
      squamous metaplastic cells (ASMT) between 2001-2003 and that had HPV-DNA testing
      and subsequent histologic and/or cytologic follow-up were evaluated. Those smears
      that were diagnosed as ASMT were reviewed and reclassified under the 2001
      Bethesda System as either ASC of undetermined significance (ASCUS) or ASC-H.
      Smears that were diagnosed as ASCUS were excluded from the study. RESULTS: The
      study included of 48 smears that were diagnosed as ASC-H. All patients with
      biopsy-proven HSIL had positive high-risk (HR)-HPV results (100% negative
      predictive value). Approximately 80% of patients with ASC-H who had biopsy
      proven, low-grade intraepithelial lesion on follow-up had positive HR-HPV
      results. Among the patients who had ASC-H with negative follow-up, 50% had
      positive HR-HPV results, and 50% had negative HR-HPV results. CONCLUSIONS: Among
      patients with ASC-H, a negative HR-HPV result was found to be an excellent
      predictor of the absence of HSIL. The results of this pilot study suggested that
      HPV-DNA testing may serve as a means to better select which patients with ASC-H
      on Pap smear should undergo colposcopic examination. This approach potentially
      may reduce medical costs and eliminate the need for routine colposcopic
      examination among patients with ASC-H Pap smears.

PMID- 16104045
TI  - Carcinoids of the pancreas: an analysis of 156 cases.
AB  - BACKGROUND: The aim of the current study was to clarify the actual
      clinicopathologic status of extremely rare pancreatic carcinoids. To date,
      statistical evaluation of such carcinoids has been hampered because an
      insufficient number of cases has prevented any reliable statistical analyses.
      METHODS: The Niigata Registry for Gut-Pancreatic Endocrinomas contains a total
      number of 156 cases of pancreatic carcinoids among 165 endocrinocarcinomas
      registered worldwide. This figure of 156 cases comprises 144 typical and 12
      atypical carcinoids, which were compared statistically with carcinoids in other
      representative sites, according to various clinicopathologic criteria. RESULTS:
      Pancreatic carcinoids made up 1.4% of the total number of registered cases (n =
      11,343) and were characteristic in the following five ways. 1) They exhibited a
      high metastatic rate (66.7%), somewhat lower than that for the ileocecum (76.1%),
      identical to that for the ileum (66.9%), and far higher than that for the total
      average of 35.7%. 2) They displayed the largest average tumor size (68.6 mm),
      followed by that for the ovary (68.2 mm), and ileocecum (46.5 mm) against a total
      average of 30.2 mm. 3) They revealed a relatively high incidence of the carcinoid
      syndrome (23.3%), almost equal to that for the ileocecum (24.1%), and exceeded by
      that for the small intestine (35.8%), when compared with that for the total
      average of 11.0%. 4) They showed a high rate of immunohistochemical detection for
      serotonin (92.9%), lower than that for the testicle (100.0%), but higher than the
      total average of 54.9%. 5) Five-year survival rate was extremely low (28.9% +/-
      16.7%) compared with those for the appendix (89.7% +/- 2.0%) and the small
      intestine (82.1% +/- 3.3%). It was noteworthy that silver impregnations in the
      pancreatic carcinoid series indicated a result identical to that for the total
      average: Grimelius argyrophilia, 84.8% versus 85.4%; argyrophil cell type, 59.1%
      versus 58.5%; and argentaffin cell type, 22.7% versus 22.3%. CONCLUSION: It may
      be said that in the treatment of patients with pancreatic carcinoids, appropriate
      procedures should be carried out with these distinguishing characteristics always
      kept in mind.

PMID- 16104046
TI  - Quantitative analysis of regional airways obstruction using dynamic
      hyperpolarized 3He MRI-preliminary results in children with cystic fibrosis.
AB  - PURPOSE: To investigate regional airways obstruction in patients with cystic
      fibrosis (CF) with quantitative analysis of dynamic hyperpolarized (HP) (3)He
      MRI. MATERIALS AND METHODS: Dynamic radial projection MRI of HP (3)He gas was
      used to study respiratory dynamics in a group of eight children with CF. Signal
      kinetics in a total of seven regions of interest (ROIs; three in each lung, and
      one in the trachea) were compared with the results of spirometric pulmonary
      function tests (PFTs). The tracheal signal intensity was used as a form of "input
      function" to normalize for input flow effects. RESULTS: A pattern of low flow
      rate in the upper lobes was observed. When the flow measurements from the
      peripheral ROIs were averaged to obtain an index of flow in the peripheral lung,
      a good correlation was found (P = 3.74 x 10(-5)) with the forced expired volume
      in one second (FEV1). CONCLUSION: These results suggest that a quantitative
      measurement of localized airways obstruction in the early stages of CF may be
      obtained from dynamic (3)He MRI by using the slope of the signal rise as a
      measure of air flow into the peripheral lung. This study also demonstrates that
      children can cooperate well with the (3)He MRI technique.

PMID- 16104047
TI  - Susceptibility to hepatitis A in patients with chronic liver disease due to
      hepatitis C virus infection: missed opportunities for vaccination.
AB  - Hepatitis A virus (HAV) superinfection is associated with a high risk of liver
      failure and death in patients with underlying chronic liver disease. Although HAV
      vaccination is recommended for all patients with chronic hepatitis C virus (HCV)
      infection, little is known about adherence to these recommendations in clinical
      practice. The aims of this study were to determine the frequency of HAV testing
      and vaccination among patients with chronic HCV infection. We conducted a
      retrospective cohort study of 1,193 patients diagnosed with chronic HCV infection
      over a 1-year period. During 1,646 person-years of follow-up, patients were seen
      by their primary care provider a median of 10.0 times (interquartile range, 4.0
      20.0). HAV antibody testing was performed in 640 subjects (53.6%), and 317
      (49.5%) of those tested were susceptible (HAV antibody negative). Only 94 of the
      1,193 patients (7.9%) received the HAV vaccine, including 26.8% of the 317
      susceptible patients, 0.9% of the 323 patients who were already immune to HAV,
      and 1.1% of the 553 subjects who were never tested. Among the 94 vaccinated
      patients, 45 received only one dose of the vaccine. Three of the unvaccinated
      patients developed acute HAV infection during follow-up, and 1 of them died of
      acute liver failure. In conclusion, despite published recommendations to
      vaccinate against HAV in patients with chronic HCV infection, we found that HAV
      testing and vaccination rates were low in clinical practice. Public health
      programs to increase awareness about HAV vaccination in patients with chronic
      liver disease are needed.

PMID- 16104048
TI  - Recapitulation of in vivo gene expression during hepatic differentiation from
      murine embryonic stem cells.
AB  - Hepatic differentiation at the molecular level is poorly understood, mainly
      because of the lack of a suitable model. Recently, using adherent monoculture
      conditions, we demonstrated the direct differentiation of hepatocytes from
      embryonic stem (ES) cells. In this study, we exploited the direct differentiation
      model to compare the gene expression profiles of ES cell-derived hepatocytes with
      adult mouse liver using DNA microarray technology. The results showed that the ES
      cell-derived hepatocyte gene expression pattern is very similar to adult mouse
      liver. Through further analysis of gene ontology categories for the 232 most
      radically altered genes, we found that the significant categories related to
      hepatic function. Furthermore, through the use of small interfering RNA
      technology in vitro, hepatocyte nuclear factor 3beta/FoxA2 was identified as
      having an essential role in hepatic differentiation. These results demonstrate
      that ES cell-derived hepatocytes recapitulate the gene expression profile of
      adult mouse liver to a significant degree and indicate that our direct induction
      system progresses via endoderm differentiation. In conclusion, our system closely
      mimics in vivo hepatic differentiation at the transcriptional level and could,
      therefore, be useful for studying the molecular basis of hepatocyte
      differentiation per se.

PMID- 16104049
TI  - Scaled interfacial activity of proteins at a hydrophobic solid/aqueous-buffer
      interface.
AB  - Contact-angle goniometry confirms that interfacial energetics of protein
      adsorption to the hydrophobic solid/aqueous-buffer (solid-liquid, SL) surface is
      not fundamentally different than adsorption to the aqueous-buffer/air (liquid
      vapor, LV) interface measured by pendant-drop tensiometry. Adsorption isotherms
      of 9 globular blood proteins with molecular weight (MW) spanning from 10 to 1000
      kDa on methyl-terminated self-assembled monolayer surfaces demonstrate that (i)
      proteins are weak surfactants, reducing contact angles by no more than about 15
      degrees at maximum solution concentrations ( approximately 10 mg/mL); (ii) the
      corresponding dynamic range of spreading pressure Pi(a) < 20 mN/m; and (iii) the
      maximum spreading pressure Pi(max) (a) for these diverse proteins falls within a
      relatively narrow 5 mN/m band. As with adsorption to the LV interface, we find
      that concentration scaling substantially alters perception of protein interfacial
      activity measured by Pi(a). Proteins appear more similar than dissimilar on a
      weight/volume basis whereas molarity scaling reveals a systematic ordering by MW,
      suggesting that adsorption is substantially driven by solution concentration
      rather than diversity in protein amphilicity. Scaling as a ratio-to-physiological
      concentration demonstrates that certain proteins exhibit Pi(max)(a) at-and-well
      below physiological concentration whereas others require substantially higher
      solution concentration to attain Pi(max)(a). Important among this latter category
      of proteins is blood factor XII, assumed by the classical biochemical mechanism
      of plasma coagulation to be highly surface active, even in the presence of
      overwhelming concentrations of other blood constituents such as albumin and
      immunoglobulin that are shown by this work to be among the class of highly
      surface-active proteins at physiologic concentration. The overarching
      interpretation of this work is that water plays a dominant, controlling role in
      the adsorption of globular-blood proteins to hydrophobic surfaces and that
      energetics of hydration control the amount of protein adsorbed to poorly water
      wettable biomaterials.

PMID- 16104050
TI  - Interfacial chemistry of class II composite restoration: structure analysis.
AB  - The gingival margins of class II composite restorations are particularly
      vulnerable to marginal leakage and secondary caries. In identifying the factors
      contributing to caries development, the molecular structure and differences in
      the structure at the proximal and gingival margins have been largely overlooked.
      The purpose of this study was to compare the molecular structure at the
      adhesive/dentin interface of the proximal and gingival walls of class II
      composite restorations. Class II preparations were cut in 12 unerupted third
      molars with a water-cooled high-speed dental handpiece. The prepared teeth were
      randomly selected for treatment with Single Bond (SB) + Z100 (3M). Teeth were
      restored, per manufacturer's directions, under humidity and temperature
      characteristic of the oral cavity. Restored teeth were kept in sterile Delbecco's
      phosphate saline for 48 h. The samples were sectioned occluso-gingivally and
      micro-Raman spectra were acquired at approximately 1.5-microm spatial resolution
      across the composite/adhesive/dentin interfaces. Samples were wet throughout
      spectral acquisition. Raman spectral characteristics at the proximal and gingival
      margins were distinctly different; the depth of demineralized dentin was 6-7
      microm at proximal margin, 12-13 microm at gingival margin. SB adhesive
      penetrated the depth of demineralized dentin in a gradient at the proximal
      margin. The "single bottle" adhesive used in this study, gradually penetrated the
      depth of the demineralized dentin at the proximal margin but failed to infiltrate
      the depth at the gingival margin, leaving a thick exposed collagen layer.

PMID- 16104051
TI  - Determination of paeoniflorin in rat plasma by a liquid chromatography-tandem
      mass spectrometry method coupled with solid-phase extraction.
AB  - A rapid, sensitive and selective liquid chromatography-tandem spectrometry method
      was developed and validated for determination of paeoniflorin in rat plasma using
      geniposide as the internal standard. The samples were pretreated with solid-phase
      extraction using Extract-Clean cartridges. Separation of paeoniflorin and IS was
      achieved on a reversed-phase C18 column (50x4.6 mm i.d.) with a mobile phase made
      up of acetonitrile and 0.05% formic acid (25:75, v/v) at a flow rate of 0.5
      mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer
      by multiple-reaction monitoring and an electrospray ionization source was
      employed as the ionization source. The lower limit of quantification obtained was
      4 ng/mL (n=6) using 200 microL plasma with an accuracy of -3.67% (relative error)
      and a precision of 4.13% (relative standard deviation). A good linearity was
      found in the range of 4-1000 ng/mL. The intra- and inter-day relative standard
      deviations in the measurement of quality control samples 10, 150 and 800 ng/mL
      ranged from 3.73 to 4.94% and from 4.31 to 6.56%, respectively. The accuracy was
      from -3.93 to -1.11% in terms of relative error. The analyte and IS were stable
      in the battery of stability studies. This method was successfully applied to a
      pharmacokinetic study of paeoniflorin after a single oral administration of 53.36
      mg/kg paeoniflorin to rats.

PMID- 16104052
TI  - Macrophages direct tumour histology and clinical outcome in a colon cancer model.
AB  - Macrophages generally constitute a major component of the tumour stroma. Although
      conventionally considered to be cytotoxic effector cells, macrophages have
      recently been described as promoters of tumour progression. The present study
      shows that selective depletion of peritoneal or liver macrophages prior to CC531
      tumour cell inoculation resulted in highly differentiated tumours in rats. In
      contrast, tumours from control rats, in which macrophages are abundantly present,
      showed a desmoplastic stromal reaction with hallmark features of malignancy, such
      as neovascularization and matrix remodelling, indicating that the presence of
      macrophages is associated with malignant histopathological differentiation.
      Remarkably, macrophage-depleted rats, bearing highly differentiated tumours, had
      a worse prognosis, as they displayed a higher tumour load and poorer survival.
      Thus, while macrophages direct tumours towards malignant tumour histology, their
      role in anti-tumour defence is important. The selective inhibition of macrophage
      functions involved in malignant progression without interfering with cytotoxic
      ability may therefore identify important new targets for cancer therapy.

PMID- 16104055
TI  - Exploring the human plasma proteome.

PMID- 16104056
TI  - Overview of the HUPO Plasma Proteome Project: results from the pilot phase with
      35 collaborating laboratories and multiple analytical groups, generating a core
      dataset of 3020 proteins and a publicly-available database.
AB  - HUPO initiated the Plasma Proteome Project (PPP) in 2002. Its pilot phase has (1)
      evaluated advantages and limitations of many depletion, fractionation, and MS
      technology platforms; (2) compared PPP reference specimens of human serum and
      EDTA, heparin, and citrate-anti-coagulated plasma; and (3) created a publicly
      available knowledge base (www.bioinformatics.med.umich.edu/hupo/ppp;
      www.ebi.ac.uk/pride). Thirty-five participating laboratories in 13 countries
      submitted datasets. Working groups addressed (a) specimen stability and protein
      concentrations; (b) protein identifications from 18 MS/MS datasets; (c)
      independent analyses from raw MS-MS spectra; (d) search engine performance,
      subproteome analyses, and biological insights; (e) antibody arrays; and (f)
      direct MS/SELDI analyses. MS-MS datasets had 15 710 different International
      Protein Index (IPI) protein IDs; our integration algorithm applied to multiple
      matches of peptide sequences yielded 9504 IPI proteins identified with one or
      more peptides and 3020 proteins identified with two or more peptides (the Core
      Dataset). These proteins have been characterized with Gene Ontology, InterPro,
      Novartis Atlas, OMIM, and immunoassay-based concentration determinations. The
      database permits examination of many other subsets, such as 1274 proteins
      identified with three or more peptides. Reverse protein to DNA matching
      identified proteins for 118 previously unidentified ORFs. We recommend use of
      plasma instead of serum, with EDTA (or citrate) for anticoagulation. To improve
      resolution, sensitivity and reproducibility of peptide identifications and
      protein matches, we recommend combinations of depletion, fractionation, and MS/MS
      technologies, with explicit criteria for evaluation of spectra, use of search
      algorithms, and integration of homologous protein matches. This Special Issue of
      PROTEOMICS presents papers integral to the collaborative analysis plus many
      reports of supplementary work on various aspects of the PPP workplan. These PPP
      results on complexity, dynamic range, incomplete sampling, false-positive
      matches, and integration of diverse datasets for plasma and serum proteins lay a
      foundation for development and validation of circulating protein biomarkers in
      health and disease.

PMID- 16104057
TI  - Data management and preliminary data analysis in the pilot phase of the HUPO
      Plasma Proteome Project.
AB  - The pilot phase of the HUPO Plasma Proteome Project (PPP) is an international
      collaboration to catalog the protein composition of human blood plasma and serum
      by analyzing standardized aliquots of reference serum and plasma specimens using
      a variety of experimental techniques. Data management for this project included
      collection, integration, analysis, and dissemination of findings from
      participating organizations world-wide. Accomplishing this task required a
      communication and coordination infrastructure specific enough to support
      meaningful integration of results from all participants, but flexible enough to
      react to changing requirements and new insights gained during the course of the
      project and to allow participants with varying informatics capabilities to
      contribute. Challenges included integrating heterogeneous data, reducing
      redundant information to minimal identification sets, and data annotation. Our
      data integration workflow assembles a minimal and representative set of protein
      identifications, which account for the contributed data. It accommodates
      incomplete concordance of results from different laboratories, ambiguity and
      redundancy in contributed identifications, and redundancy in the protein sequence
      databases. Recommendations of the PPP for future large-scale proteomics endeavors
      are described.

PMID- 16104058
TI  - A functional annotation of subproteomes in human plasma.
AB  - The data collected by Human Proteome Organization's Plasma Proteome Pilot project
      phase was analyzed by members of our working group. Accordingly, a functional
      annotation of the human plasma proteome was carried out. Here, we report the
      findings of our analyses. First, bioinformatic analyses were undertaken to
      determine the likely sources of plasma proteins and to develop a protein
      interaction network of proteins identified in this project. Second, annotation of
      these proteins was performed in the context of functional subproteomes involved
      in the coagulation pathway, the mononuclear phagocytic system, the inflammation
      pathway, the cardiovascular system, and the liver; as well as the subset of
      proteins associated with DNA binding activities. Our analyses contributed to the
      Plasma Proteome Database (http://www.plasmaproteomedatabase.org), an annotated
      database of plasma proteins identified by HPPP as well as from other published
      studies. In addition, we address several methodological considerations including
      the selective enrichment of post-translationally modified proteins by the use of
      multi-lectin chromatography as well as the use of peptidomic techniques to
      characterize the low molecular weight proteins in plasma. Furthermore, we have
      performed additional analyses of peptide identification data to annotate cleavage
      of signal peptides, sites of intra-membrane proteolysis and post-translational
      modifications. The HPPP-organized, multi-laboratory effort, as described herein,
      resulted in much synergy and was essential to the success of this project.

PMID- 16104060
TI  - Two-dimensional liquid chromatography/tandem mass spectrometry analysis of
      Gradiflow fractionated native human plasma.
AB  - One of the major challenges facing protein analysis is the dynamic range of
      protein expression within massively complex samples (Corthals, G. L. et al..,
      Electrophoresis 2000, 21, 1104-1115). In plasma this difference is as great as
      ten orders of magnitude, and this is currently beyond the range of detection
      achievable by any of the analytical techniques. Plasma has the additional
      challenge of having a few highly abundant proteins, such as albumin, which mask
      the detection of lower abundance and biologically significant proteins. The use
      of the Gradiflow BF400 as a fractionation tool to deplete highly abundant albumin
      from human plasma is reported here. A sequential three-step protocol was
      performed on five plasma samples as part of the International Plasma Proteome
      Project organised by the HUPO; four containing different anticoagulants: EDTA,
      citrate, heparin and a control sample (NIBSC); and a serum sample. Plasma from an
      alternate source also underwent fractionation and served as an in-house control.
      Time modulation between 1 and 7 h was observed for the depletion of albumin from
      these samples. Following albumin depletion, each fraction was trypsin-digested
      and the peptides were fractionated further using a 2-D LC-MS/MS. Differences in
      the total number of proteins identified for each sample were also noted.

PMID- 16104061
TI  - [Determination of Chinese traditional medicine activity eliminating superoxide
      anion radical by kinetics spectrophotometry].
AB  - A new method to determine Chinese traditional medicine activity eliminating
      superoxide anion radical by kinetic spectrophotometry was developed. It is shown
      that the optimum determination condition may be obtained when wavelength is 520
      nm, the concentration of enzyme is 4 x 10(-3) microg x mL(-1), the reaction time
      is between 2-7 min. Vitamin C activity eliminating superoxide anion radical was
      determined under the condition, and the results were identical with literature.
      The method is used to determine IC50 of Cortex Magnoliae Officinalis and Cortex
      Eucommia, and they are 7.580 and 323.800 mg x L(-1) respectively.

PMID- 16104062
TI  - [Investigation of monoclonal additional free light chains].

PMID- 16104063
TI  - [Troponins: diagnostic and prognostic value in patients with renal failure].

PMID- 16104064
TI  - [Phloroglucinol interference on bilirubin assay].

PMID- 16104065
TI  - [Severe hyperphosphatetemia].

PMID- 16104066
TI  - A typical mood stabilizers: a "typical role for atypical antipsychotics.
AB  - OBJECTIVE: To assess the potential role of atypical antipsychotics as mood
      stabilizers. METHOD: A MedLine, PsychLIT, PubMed, and EMBASE literature search of
      papers published up to December 2004 was conducted using the names of atypical
      antipsychotics and a number of key terms relevant to bipolar disorder. Additional
      articles were retrieved by scrutinizing the bibliographies of review papers and
      literature known to the authors. Data pertinent to the objective was reviewed
      according to the various phases of bipolar disorder. RESULTS: The data is most
      substantive for the use of atypical antipsychotics in mania, to the extent that
      an argument for a class effect of significant efficacy can be made. This does not
      extend to bipolar depression, however, good data is now emerging for some agents
      and will need to be considered for each individual agent as it accumulates. As
      regards mixed states and rapid cycling the evidence is thus far sparse and too
      few maintenance studies have been conducted to make any firm assertions. However,
      with respect to long-term therapy the atypical antipsychotics do have clinically
      significant side-effects of which clinicians need to be aware. CONCLUSION: Based
      on the evidence thus far it is perhaps premature to describe the atypical
      antipsychotics as mood stabilizers. Individual agents may eventually be able to
      claim this label, however, much further research is needed especially with
      respect to maintenance and relapse prevention.

PMID- 16104067
TI  - Condom maker wants to go prime time.

PMID- 16104068
TI  - Human cells capable of RNA silencing.

PMID- 16104069
TI  - Web site revised after bias complaints.

PMID- 16104070
TI  - South California residents hit back at BP over pollution.

PMID- 16104071
TI  - Financial ethics pit NIH scientists against government.

PMID- 16104072
TI  - Irradiation in the production, processing, and handling of food. Final rule.
AB  - The Food and Drug Administration (FDA) is amending the food additive regulations
      to provide for the safe use of ionizing radiation for control of Vibrio species
      and other foodborne pathogens in fresh or frozen molluscan shellfish (e.g.,
      oysters, mussels, clams, etc.). This action is in response to a petition filed by
      the National Fisheries Institute and the Louisiana Department of Agriculture and
      Forestry.

PMID- 16104073
TI  - Comparative localization of the mannose-binding lectin-2 (MBL2) gene in non-human
      primates.

PMID- 16104074
TI  - Assignment of telomeric repeat binding factor of genes TERF1 and TERF2 to Indian
      muntjac chromosome bands 1p32 and 2q33 by in situ hybridization.

PMID- 16104075
TI  - Physical mapping of the 5S rRNA in the common sea urchin, Paracentrotus lividus
      (Echinodermata: Echinoidea), by in situ hybridization.

PMID- 16104076
TI  - Treating obesity.

PMID- 16104077
TI  - Medicare and state pharmaceutical legislation.

PMID- 16104078
TI  - Meeting highlights. 65th annual scientific sessions of the American Diabetes
      Association, San Diego. Dual PPAR agonist improves glycemic control, lipids in
      type 2 diabetes.

PMID- 16104079
TI  - Safety net providers.

PMID- 16104080
TI  - Talking with patients. Bonded bridges.

PMID- 16104081
TI  - [Heartbeat--the rhythm of health].
AB  - By devoting World Health Day 1992 to the theme of heart health, it is the aim of
      the World Health Organization to increase public awareness of the worldwide
      dimensions of cardiovascular diseases, and to sound an alarm against their
      spread. Cardiovascular diseases are diseases of the highest social and medical
      importance. They are taking about 12 millions lives annually. Many victims are
      under the age of 65 years. Fortunatelly, many of the diseases could be prevented
      or postponed to the older age, as 3/4 of the cases are results of inadequate
      attitudes, knowledge, habits and behaviour. Intervention programme for prevention
      of cardiovascular diseases and other non-communicable diseases conducted in Novi
      Sad has demonstrated its potential role regarding the leading risk factors,
      incidence and mortality from acute miocardial infarction and stroke.

PMID- 16104082
TI  - [The role and value of perfusion parameters in clinical discrimination of "cold"
      thyroid nodes].
AB  - The aim of the study was to investigate if the perfusion parameters can be of
      value in differential diagnosis of "cold" thyroid nodes. This procedure was
      performed in 60 patients with "cold" unilateral nodes. The quantitative
      parameters of perfusion through the "cold" nodes were obtained by our own
      computer programme. The parameters of perfusion which gave the most impressive
      results are shown in this study. The ratio of perfusion between the node and
      healthy thyroid lobe was significantly higher in carcinomas (0.8) than in benign
      "cold" nodes: cysts (0.1), autommune thyroid diseases and benign solid goiters
      (0.4). The radioactivity increasing rate in node was significantly higher in
      carcinomas (2.7) than in benign nodes: Cysts (1.3), autoimmune thyroid diseases
      (1.5) and solid benign goiters (1.6). The ratio of radioactivity increasing rate
      between the node and healthy thyroid lobe was also significantly higher in
      carcinomas (0.9) than in other "cold" benign lesions (0.3).

PMID- 16104083
TI  - [Our experiences in the treatment of myelodysplastic syndromes].
AB  - From 1987 an abrupt increase of the number of patients presented with MDS has
      been registered. We present our experiences in the treatment of 42 patients. The
      number of the male patients was two times larger than of the females. They were
      most frequently diagnosed as having RAB (43%) and RAEBt (28.5%). RA was found in
      14%, RARS in 9.5% and CMML. in only 5% of the cases. The treatment was
      accomplished with ultralow (3 mg/m2/12h s.c.) and low doses (10 mg/m2/12h s.c.)
      of ARA-C in 75% of the patients with RAEBt and 44.4% with RAEB, while the CMML
      group received hydroxyurea. The treatment improved hematologic results but the
      complete remission lacked. In 23.8% of the cases the disease developed into acute
      nonlymphoblastic leukemia. Patients excepted from cytostatic therapy were
      observed by the use of androgens, anabolics, vitamin A+D3 and transfusion of
      separated erythrocytes. In 38% of the patients with MDS a lethal outcome
      followed. Life of those in whom the disease developed into acute leukemia in
      statistically significatly shorter (p < 0.05). There was no statistically
      significant difference in the survival rate between the treated and nontreated
      patients (p > 0.05). Further treatment of these patients includes, apart from
      ultralow doses of ARA-C, the use of retinoic acid, a growth factor (GM-CSF) and
      bone marrow transplantation.

PMID- 16104084
TI  - [Saluresis in hypothermia and posthypothermia under the influence of LiCl].
AB  - Lithium compounds administered into rats' organisms in euthermia elicited
      accelerated urinary excretion of physiological cations, especially the Na and K
      ones. Homeothermic organisms in hypothermia, returnig from hypothermia and in
      posthypothermia showed considerable caliuresis with delayed excretion of Na
      during the following days. By way of gastric filling lithium load (in a form of
      water LiCl solution, with concentration of 0.2 n and the amount of 3.0 ml/100 cm2
      ger body surface) administered to rats in deep hypothermia (17 degrees C - 19
      degrees C measured high in the sigma), recovering of hypothermia (4 h) and in
      posthypothermia (20 h) did not elicit delayed natriuresis but efficiency of
      lithium and hypothermia had been summarised (clearly enhanced natriuresis and
      extremely enhanced caliuresis as a summarised efficiency).

PMID- 16104085
TI  - [Immunocytochemical study of the noradrenaline and adrenaline-storing cells of
      the adrenal medulla under hypoxic stress].
AB  - Laboratory rats were exposed to the effect of intermittent hypoxia every other
      day over the 11-day period. Condition characteristics of 7000 m of height above
      see level were imitated. The indirect immunofluorescence staining was used in
      order to study morphodynamic turnover of adrenalin and noradrenalin cells. The
      results obtained have shown that the contents of adrenalin and noradrenalin cells
      in the medulla of the adrenal gland were mobilized. The discussion in the paper
      favours the probability that bioeffect of hypoxia may be expressed via the
      catecholamine system.

PMID- 16104086
TI  - [Serotonin syndrome--a case account].
AB  - Beside a large number of pharmaceuticals available on our market having an impact
      on serotonergic transmission, selective serotonin reuptake blocker inhibitors
      (fluvoxamine, fluoxetine) and a selective reversible monoaminooxidase inhibitor
      (moclobemide), have been included recently. The combination of the drugs can in
      certain conditions cause a central serotonergic hyperactivity, i.e. the serotonin
      syndrome. The study describes the development of the serotonin syndrome following
      an abrupt replacement of trazodone by moclobemide. The diagnosis was made on the
      basis of the anamnesis, clinical features, course and outcome of the disorder and
      diagnostic criteria suggested in the literature. The importance of the
      prevention, early detection and timely management of the serotonin syndrome have
      been reflected in the fact that some of the outcomes described were fatal,
      although this state most frequently remits spontaneously after the replacement of
      the drug therapy.

PMID- 16104087
TI  - [Charcot-Marie-Tooth disease and stroke].
AB  - The association between HMSN and other diseases is not so frequent, but it is not
      unknown. Reports about the association between HMSN and cardiac disturbances are
      controversial, although a growing number of such cases is now being reported. We
      describe two cases of HMSN type 2 with stroke (one ischemic and one haemoragic
      type), which, to our knowledge, has never previously been reported.

PMID- 16104088
TI  - [Child trauma in Vojvodina].
AB  - Trauma represents for quite a long period a significant problem in child health
      care in Vojvodina. For better understanding of the trends of trauma in overall
      registrated child morbidity and mortality includingoutpatient and hospital cases
      we used the data derived from retrospective study fora period from 1979 to 1988.
      Analyzing the structure of ten leading groups of illnesses in the outpatient
      groups of children by the age of 6 years, injuries and intoxications were on the
      sixth position with the frequency of 2% and for the same period had a progressive
      increase with the dynamic index of 105.30. The percentage of the injuries and
      intoxications in the registrated outpatient morbidity of children from 6 to 14
      years was 5-5.5% which put them on the fifth position at the list of ten leading
      groups of illnesses. During the same period of time trauma registered in the
      hospital morbidity showed decrease with the dynamic index of 86.12 and was on the
      fourth position with 7-8% of overall morbidity. There are on the average 74 child
      deaths annually in Vojvodina caused by injuries and intoxications.

PMID- 16104089
TI  - [Differential diagnosis of hemangiomas, malignant processes and cystic formations
      in the liver by scintigraphy].
AB  - The aim of the study was determination and verification of the diagnosis in
      patients with liver hemangiomas already detected by ultrasonography. Scintigraphy
      was performed in 92 patients after equilibration of marked erythrocytes with tin
      pyrophosphate (Sn-PYP) scintigraphy and a static scintigram of the liver (early
      and late after 2-3 h) were obtained. The clinical treatment of all patients
      involved classical scintigraphy of the liver with 99mTc colloid. After the
      treatment fragmentary accumulation of radioisotopes was detected on early
      scintigrams and were markedly evident on late ones in areas presenting vascular
      formations manifested as foca-coll zones on classical scintigram.

PMID- 16104094
TI  - [Epidemiological characteristic of basocellular skin epitheliomas treated at the
      Department of Dermatovenereal Diseases in Novi Sad].
AB  - The authors review some of the epidemiological characteristics of epithelioma
      basocellulare (EB) of the skin, showing the incidence of 2.39% of the cases
      treated for EB of the skin from 1984 to 1990, derived from the total of 61,384
      initial examinations carried out in this period at the Department of
      Dermatovenereal Diseases in Novi Sad. The mean age of the patients was 64.42, the
      male-female ratio was slightly in favor of the females, 1:1.25. As for
      localization, EB of the skin were most frequently found on the face, head and
      neck (87.16%). Regarding occupation of the patients on the top were retired
      people (47.17%) and agricultural workers (33.02%) and regarding the place of
      living, most were found in the rural population (68.07). The mean time the
      treated patients came for a check-up was 1.26 year after the onset of the tumor.
      Relapses were found in 18 cases (1.23%). The mean time of their occurrence after
      the rtg therapy was 1.9 year. Familial predisposition for skin tumors was
      detected in 232 cases (15.79%).

PMID- 16104095
TI  - The extracellular actin scavenger system in trauma and major surgery. Clinical
      and experimental studies.

PMID- 16104096
TI  - Flanker effects on motor output and the late-level response activation
      hypothesis.
AB  - When participants must respond to a relevant central target and ignore irrelevant
      flanking stimuli, the flankers produce a flanker compatibility effect on
      behavioural measures. Current accounts of the flanker compatibility effect assume
      that both target and flanker stimuli affect response activation. This idea is
      supported by electrophysiological studies, which show that irrelevant flanker
      stimuli can affect the motor system. The present experiments examined the
      characteristics of flanker effects on the motor system by analysing the details
      of the motor output with response force measures. A total of 60 participants
      responded in the flanker task to arrows (Experiment 1) or letters (Experiment 2).
      Reaction time as well as response force increased on incompatible trials.
      Analyses of the distribution of incorrect activation revealed that both response
      times and correct motor output increased with the amount of incorrect activity.
      However, the flanker compatibility effect was only marginally modulated by
      incorrect activity. Results suggest that the largest part of the flanker
      compatibility effect cannot be attributed to response activation and competition
      at late levels of the response system.

PMID- 16104097
TI  - Naming from definition: the role of feature type and feature distinctiveness.
AB  - The present paper evaluates the contribution of feature type and feature
      distinctiveness to naming of living and nonliving things using a naming from
      definition task. Normal subjects read verbal descriptions containing features
      varying in type (i.e., sensory vs. functional) and distinctiveness (i.e.,
      distinct vs. shared) and were asked to name the concept described and to select
      the three features that most contributed to their answer. Main results showed
      that sensory features were selected more often than functional features to
      support naming living things and that, independent of feature type, more distinct
      features were selected to support naming more often than shared features. Results
      are discussed considering the implications for understanding naming and for
      neuropsychological evaluation.

PMID- 16104098
TI  - Inhibition of return following instructions to remember and forget.
AB  - Inhibition of return (IOR) refers to slowed responding to a target that appears
      in the same rather than in a different location as a preceding peripheral onset
      cue. This study examined IOR as a function of whether the peripheral onset cue
      was a word that participants were directed to remember or forget. Using a
      modified item-method directed forgetting paradigm, words appeared one at a time
      to the left or right, followed by a remember or forget instruction. A target dot
      was then presented either in the same peripheral location as the preceding word
      or in a different location; participants made a speeded response to localize this
      target. Confirming compliance with the memory instructions, recall tests that
      alternated with blocks of IOR trials (Experiment 1) revealed few intrusions of to
      be-forgotten words, and a final recognition test (Experiments 1 and 3) revealed
      more hits for to-be-remembered words than for to-be-forgotten words. Reaction
      times to the target dot revealed greater magnitude IOR following to-be-forgotten
      words than following to-be-remembered words (Experiments 1 and 3). Moreover, when
      compared to baseline IOR values (Experiment 2), it appeared that this difference
      resulted from a magnification of IOR following forget instructions and a
      reduction in IOR following remember instructions. These results demonstrate the
      usefulness of IOR as an index of memorial processes and suggest that attentional
      orienting may play a role in the remembering and forgetting of words presented in
      peripheral visual locations.

PMID- 16104099
TI  - Sex differences in eye gaze and symbolic cueing of attention.
AB  - Observing a face with averted eyes results in a reflexive shift of attention to
      the gazed-at location. Here we present results that show that this effect is
      weaker in males than in females (Experiment 1). This result is predicted by the
      'extreme male brain' theory of autism (Baron-Cohen, 2003), which suggests that
      males in the normal population should display more autism-like traits than
      females (e.g., poor joint attention). Indeed, participants' scores on the Autism
      Spectrum Quotient (Baron-Cohen, Wheelwright, Stott, Bolton, & Goodyear, 2001)
      negatively correlated with cueing magnitude. Furthermore, exogenous orienting did
      not differ between the sexes in two peripheral cueing experiments (Experiments 2a
      and 2b). However, a final experiment showed that using nonpredictive arrows
      instead of eyes as a central cue also revealed a large gender difference. This
      demonstrates that reduced orienting from central cues in males generalizes beyond
      gaze cues. These results show that while peripheral cueing is equivalent in the
      male and female brains, the attention systems of the two sexes treat
      noninformative symbolic cues very differently.

PMID- 16104100
TI  - Prior belief and polarity in multicue learning.
AB  - We report two experiments in which participants are trained using a multicue
      probability learning (MCPL) task, which attempts to simulate the acquisition of
      expert judgement by experience in the real world. Participants were asked to
      predict performance in certain occupations given a profile of personality test
      results with trial-by-trial outcome feedback. Only some cues were relevant, and
      the polarity of the cues (positive or negative predictors) was unspecified. In
      addition, 25% of random noise was added to the feedback to simulate real world
      uncertainty. The main factor of interest was that the role of prior belief
      (determined in a separate study of stereotypes) interfered with the learning
      process. Experiment 1 failed to find any influence of prior belief in the cues
      that were irrelevant to the criterion being trained. However, in Experiment 2
      people learned to use the relevant cues better when their effect conformed with
      rather than conflicted with prior belief Both experiments showed strong effects
      of cue polarity, with positive predictors much more easily learned. The results
      are discussed with reference to the cognitive processes involved in MCPL and
      closely related tasks.

PMID- 16104101
TI  - Refractory effects in picture naming as assessed in a semantic blocking paradigm.
AB  - In the cyclic semantic blocking paradigm participants repeatedly name sets of
      objects with semantically related names (homogeneous sets) or unrelated names
      (heterogeneous sets). The naming latencies are typically longer in related than
      in unrelated sets. In Experiment 1 we replicated this semantic blocking effect
      and demonstrated that the effect only arose after all objects of a set had been
      shown and named once. In Experiment 2, the objects of a set were presented
      simultaneously (instead of on successive trials). Evidence for semantic blocking
      was found in the naming latencies and in the gaze durations for the objects,
      which were longer in homogeneous than in heterogeneous sets. For the gaze-to
      speech lag between the offset of gaze on an object and the onset of the
      articulation of its name, a repetition priming effect was obtained but no
      blocking effect. Experiment 3 showed that the blocking effect for speech onset
      latencies generalized to new, previously unnamed lexical items. We propose that
      the blocking effect is due to refractory behaviour in the semantic system.

PMID- 16104102
TI  - Episodic temporal generalization: a developmental study.
AB  - Groups of 5-year-olds, 10-year-olds, and adults completed either an episodic
      temporal generalization task, in which no stimuli were repeated, or a repeated
      standard temporal generalization task, in which there was a fixed standard that
      was repeated on every trial. Significant developmental improvements were found on
      both tasks. In both tasks, gradients of performance over two different stimulus
      ranges superimposed well when plotted on the same relative scale. Performance was
      similar for the adults and 10-year-olds across tasks, but the 5-year-olds
      performed better on the repeated standard task. These findings suggest that
      perceptual processes are a source of scalar variability in timing, and that there
      are developmental changes in levels of such variability.

PMID- 16104103
TI  - Exploring trial-by-trial modulations of the Simon effect.
AB  - The present study investigates sequential modulations of the Simon effect. The
      Simon effect involves faster responses to spatially corresponding than to
      noncorresponding stimuli, even when stimulus position is irrelevant. Recently,
      the Simon effect has been shown to decrease or to disappear after
      noncorresponding predecessor trials. Possible explanations for these sequential
      modulations include (a) the gating of position-based response activation
      (conflict monitoring), (b) repetition or alternation effects, and (c) the
      interaction between feature integration (binding) processes and stimulus-response
      (S-R) correspondence. Three experiments tested different predictions of these
      models by comparing Simon effects after neutral trials with those after
      corresponding and noncorresponding trials, respectively, and by varying the
      stimulus-onset asynchrony (SOA) between and within experiments. Experiments 1 and
      2 revealed large Simon effects after corresponding trials, intermediate Simon
      effects after neutral trials, and small (or no) Simon effects after
      noncorresponding trials. Moreover, some systematic effects of S-R repetitions and
      S-R alternations were observed. Finally, the sequential modulations were maximal
      at short SOAs and decreased with increasing SOA, but still occurred at an SOA of
      6 seconds. The results seem to exclude repetition or alternation effects as the
      main cause of sequential modulations of the Simon effect, but both conflict
      monitoring and binding may contribute to these effects.

PMID- 16104104
TI  - Unsupervised categorization and category learning.
AB  - When people categorize a set of items in a certain way they often change their
      perceptions for these items so that they become more compatible with the learned
      categorization. In two experiments we examined whether such changes are extensive
      enough to change the unsupervised categorization for the items-that is, the
      categorization of the items that is considered more intuitive or natural without
      any learning. In Experiment 1 we directly employed an unsupervised categorization
      task; in Experiment 2 we collected similarity ratings for the items and inferred
      unsupervised categorizations using Pothos and Chater's (2002) model of
      unsupervised categorization. The unsupervised categorization for the items
      changed to resemble more the learned one when this was specified by the
      suppression of a stimulus dimension (both experiments), but less so when it was
      almost specified by the suppression of a stimulus dimension (Experiment 1,
      nonsignificant trend in Experiment 2). By contrast, no changes in the
      unsupervised categorization were observed when participants were taught a
      classification that was specified by a more fine tuning of the relative salience
      of the two dimensions.

PMID- 16104106
TI  - 'MVP' bill would bring P4P incentives to Medicare.

PMID- 16104105
TI  - Shifts of spatial attention in perceived 3-D space.
AB  - Previous studies have shown that spatial attention can shift in three-dimensional
      (3-D) space determined by binocular disparity. Using Posner's precueing paradigm,
      the current work examined whether attentional selection occurs in perceived 3-D
      space defined by occlusion. Experiment 1 showed that shifts of spatial attention
      induced by central cues between two surfaces in the left and right visual fields
      did not differ between the conditions when the two surfaces were located at the
      same or different perceptual depth. In contrast, Experiment 2 found that
      peripheral cues generated a stronger cue validity effect when the two surfaces
      were perceived at a different rather than at the same perceptual depth. The
      results suggest that exogenous but not endogenous attention operates in perceived
      3-D space.

PMID- 16104107
TI  - Medicaid drug system, AWP policies are 'broken'.

PMID- 16104108
TI  - [Cause of death: from primary disease to direct cause of death].
AB  - Following the death of a patient, the treating physician in the Netherlands is
      required to fill out two forms. Form A, which is the certificate of death and
      Form B, which is used by the Statistics Netherlands to compile data on causes
      ofdeath. The latter form often poses difficulty for the physician with respect to
      the primary cause of death. This applies particularly to cases of sudden death,
      which account for one third of all deaths in the Netherlands. As a result, the
      statistical analyses appear to lead to an incorrect representation of the
      distribution of causes of death. A more thorough investigation into the primary
      cause of death is desirable, if necessary, supported by a request for an autopsy.
      The primary cause of death is to be regarded as the basic disease from which the
      cascade of changes ultimately leading to death originated.

PMID- 16104109
TI  - [Predictable risk of cerebral infarction following a transient ischaemic attack].
AB  - To date most studies that have addressed prognostic factors in patients who have
      had a transient ischaemic attack (TIA) have determined the risk of cerebral
      infarction during the first 3 years following TIA. Two recent studies have
      investigated the very long-term and very short-term risks. The long-term study
      found that the risk unexpectedly increased after 3 years. The short-term study
      found the very early risk of cerebral infarct (< 7 days) to be substantial at
      10%. The proposed ABCD score enables the physician to easily identify patients at
      particularly high risk: (A) 1 point for age > or =6o years, (B) 1 for systolic
      blood pressure >140 mmHg and/or diastolic pressure >90 mmHg, (C) 2 points for
      unilateral weakness, 1 for speech disturbance without weakness, (D) 2 points for
      an attack lasting > or =1 h and 1 point for an attack lasting 10-59 min. A
      patient with a total score of 5 has a risk of 12.1% of developing a cerebral
      infarct within 7 days. In a patient with a score of 6 this risk is 31.4%.

PMID- 16104110
TI  - [Clinical implications of new insights into the regulation of bone resorption].
AB  - It has recently been discovered that the receptor activator of nuclear kappaB
      ligand (RANKL) plays a key role in the activation, differentiation and
      proliferation ofosteoblasts. The effects of RANKL are counteracted by the decoy
      receptor osteoprotegerin (OPG), which protects against bone resorption by
      preventing RANKL from coupling to its receptor RANK. An increase in the balance
      between RANKL and OPG leads to increased bone resorption (both locally and
      generalised), e.g. in patients with postmenopausal osteoporosis, glucocorticoid
      induced osteoporosis, multiple myeloma, other malignancies with skeletal
      metastases, or rheumatoid arthritis. The development of new anti-osteoporotic
      drugs, based on the restoration of the imbalance between RANKL and OPG, may be a
      breakthrough in optimising the treatment of patients with bone diseases. However,
      the results of studies on fracture reduction, the safety profile, the costs of
      the new drugs and their comparison with bisphosphonates, currently the gold
      standard in osteoporosis treatment, must be awaited.

PMID- 16104111
TI  - [The guideline 'Diagnosis and treatment of peripheral artery disease of the lower
      extremities' is limited to scientifically proven recommendations].
AB  - The guideline in question is the product of a cooperative effort by the Dutch
      Society of Vascular Surgery and the Section on Interventional Radiology of the
      Dutch Society of Radiology; it focuses on the diagnostic work-up and initial
      treatment. The guideline presents an outline of several diagnostic modalities as
      well as endovascular and surgical interventions. Based on the principle of
      evidence-based medicine, it provides the clinician with an excellent outline of
      the diagnostic and therapeutic possibilities. A minor disadvantage of this method
      is that the difference between acute arterial thrombosis and arterial emboli, as
      well as the relation between symptoms and the localisation of occlusions, the age
      of the patient and co-morbidity, are not always clear.

PMID- 16104112
TI  - [The guideline 'Diagnosis and treatment of peripheral artery disease of the lower
      extremities' of The Netherlands Surgical Society].
AB  - The guideline 'Diagnosis and treatment of peripheral artery disease of the lower
      extremities' describes the diagnostic work-up and treatment of patients with
      peripheral artery disease of the legs. The text is the result of a cooperative
      effort of the Dutch Society of Vascular Surgery and the Section of nterventional
      Radiology of the Dutch Society of Radiology. A diagnosis of 'peripheral artery
      disease' can be made by measuring the ankle/brachial index. Additional
      investigations are only necessary ifa plan for invasive treatment must be drawn
      up. The first line of treatment in patients with intermittent claudication is
      walking exercise. If the results are unsatisfactory, percutaneus transluminal
      angioplasty (PTA) or surgery can be performed. In case of critical ischaemia,
      revascularisation is mandatory to prevent an amputation. In selected cases,
      percutaneous intentional endovascular revascularisation is a good alternative to
      bypass surgery. In patients with acute ischaemia in whom the vitality of the leg
      is not threatened, intra-arterial thrombolysis can be carried out as an
      alternative to surgery. An inhibitor of platelet aggregation such as
      acetylsalicylic acid and a statin should be prescribed to patients with
      peripheral artery disease. Only in case of venous bypass surgery should a
      coumarin derivative and a statin be prescribed for 2 years, while the bypass is
      controlled periodically for 6 months by duplex examination.

PMID- 16104113
TI  - [3D-navigation in nasal sinus surgery].
AB  - Mechanical, infra-red and electrofrequency 3D-navigation equipment enables the
      visualisation of a probe in a patient in the three dimensions ofa CT-scan. Such a
      system guarantees better orientation in difficult anatomical areas. 3D navigation
      is particularly suitable for nasal-sinus surgery as the bony structures are
      reproduced in precise detail on a CT-scan and bone parameters do not change
      during operation. These technical developments mean that not only the indications
      for operation but also the surgical approach have greatly altered. In functional
      nasal-sinus surgery the aim is to open up the sinus by removing all those
      structures which may hinder drainage. The mucous membrane with its mucociliary
      transport is spared and goes on to heal. - Prior to operation the patient's
      anatomical landmarks are tracked and spatially linked to the corresponding points
      on the CT-scan. The coordinates of these points are registered on a computer. A
      probe is moved around within the spaces, its coordinates are calculated and their
      position shown on a CT-scan. The patient's head is fixed in a frame that is able
      to move with the head. The advantage of the 3D-navigation system is its surgical
      and anatomical orientation. Disadvantages are its cost and, to a lesser extent,
      time requirements and the size of the equipment.

PMID- 16104114
TI  - [From gene to disease; incontinentia pigmenti and the NEMO-gene].
AB  - Incontinentia pigmenti (IP; MIM308310) is a rare neurocutaneous X-dominant
      inherited disorder. Besides skin and neurological abnormalities, there is also
      ophthalmologic and dental involvement. The first stage is characterised by
      inflammation and apoptosis of the skin and central nervous system. The first
      stage consists of vesicles and the second of verrucous elements; the third stage
      is characterised by hyperpigmentation while the fourth is characterised by
      slightly atrophic hypopigmentations. The skin abnormalities follow the lines of
      Blaschko. The disorder is observed almost exclusively in girls, but diseased boys
      are more seriously affected. The IP gene is localised on chromosome Xq28.
      Mutations in the NEMO-gene are responsible for IP. This gene codes for the
      nuclear factor-KB essential modulator protein (NEMO; synonym: inhibitor kappaB
      kinase (IKK)y). In the absence of serious neurological symptoms, the prognosis is
      not poor.

PMID- 16104115
TI  - [The correlation of age and comorbidity with therapy and survival in cancer
      patients in North-Brabant and North-Limburg, 1995-2001].
AB  - The proportion of elderly cancer patients has increased considerably. This means
      that more patients are being diagnosed with one or more serious concomitant
      condition which may complicate the treatment of cancer. Little is known about
      treatment outcomes, as elderly patients with comorbidity are often excluded from
      clinical trials. The Eindhoven Cancer Registry has been registering serious co
      morbidity in North-Brabant and North-Limburg in the Netherlands since 1993. Using
      data from patients diagnosed with cancer in 1995-2001, the correlation between
      age and comorbidity and choice of therapy and survival rates was described. Very
      elderly patients or patients with co-morbidity often were not treated in
      accordance with the guidelines. Elderly patients with localized lung cancer or
      prostate cancer underwent less surgery as often and elderly patients with
      colorectal cancer, breast cancer or ovarian cancer received less adjuvant
      chemotherapy or radiotherapy than younger patients. The prognosis was often worse
      for elderly patients than for younger patients, and the presence of co-morbidity
      decreased survival in most types of tumour. The question remains whether the
      prognosis for elderly patients with cancer would improve if more of them were
      treated in accordance with the guidelines, or if this will only lead to more
      complications.

PMID- 16104116
TI  - [Quality of nuchal transluccency measurements: an exploratory study into their
      performance and evaluation].
AB  - OBJECTIVE: To investigate the quality of nuchal translucency measurements that
      were done as part of a randomised study into screening for Down's syndrome.
      DESIGN: Exploratory. METHOD: In the period May 2001-April 2003, 396 nuchal
      translucency measurements were done by 55 sonographers in 13 different echography
      centres. The sonographers were questioned in writing regarding their training and
      experience, the procedure and technique used, and the quality assurance. A filled
      in questionnaire was received from 42 sono0 images at random from the
      2710measurements (70%o) that had been made in 6 centres. These were evaluatedby 3
      experts on the basis of the 5 criteria that are used by the Fetal Medicine
      Foundation (FMF). Each measurement was given 2 points for every criterion that
      was fulfilled, after which the average of the 3 scores was calculated. RESULTS:
      Of the 42 respondents, 88% had taken a nuchal translucency measurement course and
      45% were certified by the FMF. Calipers were placed incorrectly by 50% of the
      respondents; 62% of the respondents mentioned the absence of an intern quality
      check. Concerning the quality-assessment of the nuchal translucency measurements,
      the assessors unanimously considered i3%o of the 30 images to be suitable for
      prenatal screen4ngand 43% to be unsuitable; their opinions as to the remaining
      images differed. The average quality mark was 4.7. CONCLUSION: Many nuchal
      translucency measurements did not fulfil the quality criteria that are imposed in
      order to make the measurement reliable as a screening test. There was a lack of
      quality securance in the echography centres.

PMID- 16104117
TI  - [Severe contact-allergy dermatitis due to poison ivy--a plant that is rarely
      encountered in The Netherlands; a family history].
AB  - In successive years, three members of the same family (a man and woman aged 46
      years and their son, aged 20) constantly developed severe pruritic, erythematous,
      vesicular and bullous dermatitis in the spring and summer after working in the
      garden. Although the findings were consistent with a photophytotoxic dermatitis,
      the causative plant remained unclear. Oral therapy with high doses ofprednisolone
      was necessary. When the man travelled to the USA and visited a doctor there, he
      recognised the symptoms as those of contact dermatitis caused by poison ivy
      (Toxicodendron radicans), a plant that is found sporadically in the wild state in
      Europe. Their grandparents had brought the plant back from a trip to the USA and
      planted it in the garden because of the beautiful fall colours. The family
      identified the plant via a search on Internet and eliminated it from the garden
      completely. Since then, the family has no longer suffered from contact-allergy
      dermatitis.

PMID- 16104118
TI  - [Physostigmine for the immediate treatment of a patient with the central
      anticholinergic syndrome induced by cocaine cut with atropine].
AB  - A 34-year-old man was admitted in a coma after a nightlong abuse of cocaine and
      alcohol, whereupon he fell and convulsed at home. There was a fracture of the
      nose, hyperpyrexia, tachycardia and hypertension. Dry mouth and mydriasis were
      suggestive of anticholinergic poisoning. Physostigmine 3 mg were slowly
      administered intravenously, followed by complete neurological recovery and
      normalisation of the body temperature. There was no brain damage. Cocaine and
      atropine were found in the patient's urine. Several users of cocaine in various
      European countries have recently developed a central anticholinergic syndrome due
      to adulteration of cocaine with atropine. In the presence of indications for such
      an intoxication, physostigmine is the antidote of first choice.

PMID- 16104119
TI  - [Increase in number of operations for stress urinary incontinence].
AB  - Since the introduction of the minimally invasive tension-free vaginal tape (TVT)
      the number of operations performed for treatment of stress urinary incontinence
      has increased dramatically from over 1600 in 1999 to more than 4200 in 2003. Both
      gynaecologists and urologists now perform more TVTs and fewer Burch
      colposuspensions and Marshall-Marchetti-Krantz operations. This increase was
      apparent before data from proper studies on the effectiveness of the TVT were
      available. With the increasing popularity of a new and more easily performed
      variant of the TVT, the transobturator tape, the number of operations is likely
      to increase further. Gynaecologists and urologists must remain critical in the
      recommendation of these operations, since complications such as urinary retention
      and overactive-bladder syndrome with urgency or urge incontinence are well known
      and difficult to treat. Pelvic-floor physiotherapy, which is accepted by
      gynaecologists, urologists and general practitioners, should remain the first
      line treatment for stress urinary incontinence.

PMID- 16104120
TI  - [Diagnostic image (236). A woman with acute unilateral swelling of the face].

PMID- 16104121
TI  - [Diagnostic image (236). A woman with acute unilateral swelling of the face].

PMID- 16104122
TI  - [Deliberate termination of life in newborns in The Netherlands; review of all 22
      reported cases between 1997 and 2004].

PMID- 16104123
TI  - Pathophysiology of gastroesophageal reflux disease.
AB  - From a pathophysiologic viewpoint, GERD results from the excessive reflux of
      gastric contents into the distal esophagus. Under normal conditions, this is
      prevented as a function of the antireflux barrier at the EGJ, the integrity of
      which is dependent on the delicate interplay of a host of anatomic and
      physiologic factors, including the integrity of the LES, TLESR, and anatomic
      degradation of the EGJ inclusive of but not limited to hiatus hernia.
      Considerable investigative focus is aimed at describing the subtle aberrations of
      the EGJ that may contribute to the root causes of GERD. The net result is an
      increased number of reflux events, an increasing diversity of potential
      mechanisms of reflux, and a diminished ability of the stomach to selectively vent
      gas, as opposed to gas and gastric juice, during TLESR. Once reflux occurs, the
      duration of resultant esophageal acid exposure is determined by the effectiveness
      of esophageal acid clearance, the dominant determinants of which are peristalsis,
      salivation, and, again, the anatomic integrity of the EGJ. Approximately half of
      patients who have GERD have abnormal acid clearance and the major contributor to
      this is hiatus hernia. Abnormalities of acid clearance probably are the major
      determining factor influencing which patients who have GERD are most prone to
      developing esophagitis as opposed to symptomatic GERD. In summary, GERD is a
      multifactorial process involving physiologic and anatomic abnormalities. These
      abnormalities exhibit a complicated interplay that degrades the ability of the
      EGJ to contain gastric juice within the stomach and to clear the esophagus of
      gastric juice effectively once reflux has occurred.

PMID- 16104124
TI  - Bile reflux in the constellation of gastroesophageal reflux disease.
AB  - Gastric acid and bile acids are a particularly noxious combination when they
      interact with the mucosa of the upper intestinal tract. There is a critical pH
      range, between 3 and 6, in which bile acids exist in their soluble, un-ionized
      form, can penetrate cell membranes, and accumulate within mucosal cells. At a
      lower pH, bile acids are precipitated, and at a higher pH, bile acids exist in
      their noninjurious ionized form. Experimental, clinical, and immunohistochemical
      studies show that acid and bile reflux are increased in patients who suffer from
      GERD, are the key factor in the pathogenesis of Barrett's esophagus, and possibly
      are related to the development of esophageal adenocarcinoma.

PMID- 16104125
TI  - Gastroesophageal reflux and cancer.
AB  - The causal relationship between GERD and esophageal adenocarcinoma, although
      unclear just a few decades ago, now is established fairly well. The physiologic
      changes and the biocellular alterations of the damaged esophageal mucosa are
      documented better. Despite this knowledge, the dramatic increase in the incidence
      of esophageal cancer cannot be explained. The absolute risk of esophageal
      adenocarcinoma arising from GERD is low, and, at present, does not justify
      population-screening programs. Still, with the notion that adenocarcinoma of the
      esophagus is an aggressive cancer once documented, important questions still are
      in need of answers for patients suffering from reflux symptoms. Patients who have
      reflux disease are not necessarily symptomatic. It remains unclear if patients
      experiencing reflux symptoms should undergo mandatory endoscopy with biopsies at
      the esophagogastric junction. Furthermore, metaplasia of the lower esophagus
      often is not readily recognizable at endoscopy, and only biopsies can document
      abnormal histology. A severe and prolonged history of reflux always should orient
      to the possibility of a reflux-related columnar-lined esophagus. Once documented,
      Barrett's esophagus needs to be seen as a premalignant condition not necessarily
      leading to adenocarcinoma formation; despite their increased risk of tumor
      formation, most patients who have Barrett's esophagus die of other causes. During
      regular endoscopic follow-up, multilevel circumferential biopsies should document
      the evolution of the histologic changes in the lower esophagus and at the
      gastroesophageal junction of these patients. It is the only method available to
      document the appearance of dysplasia. It still is unclear if medicine or surgery
      provides the best quality of life and the best protection against the development
      of dysplasia and the possible progression toward adenocarcinoma formation when
      intestinal metaplasia is present in the esophagus.

PMID- 16104126
TI  - The spectrum of pulmonary symptoms due to gastroesophageal reflux.
AB  - Most asthmatics have GER, and the evidence is strong that GER plays an important
      role in some patients who have asthma. Despite sophisticated study methods and
      technologically advanced diagnostic tests, the results of published studies on
      mechanisms have failed to provide a diagnostic test with a degree of certainty
      great enough to identify which patients have GER-induced or GER-exacerbated
      asthma and which patients will respond to antireflux therapy. The difficulties
      involved in establishing a definite cause-and-effect relationship between GER and
      asthma are real. Even positive results on such direct tests as sputum inspection
      and scintigraphic monitoring, both of which establish reflux into the
      tracheobronchial tree, do not necessarily establish cause or effect and cannot be
      used to predict outcomes. Ambulatory esophageal pH testing can suggest, but
      cannot prove, the diagnosis of GER-induced asthma, and pH testing cannot be
      relied on safely to make clinical decisions. A trial of a proton pump inhibitor
      (PPI) is indicated to assess if asthma improves subjectively and objectively, but
      the dose must be high enough to prevent even silent esophageal acid exposure, and
      the duration must be long enough to allow for detection of even subtle trends in
      subjective and objective respiratory improvement. Antireflux surgery remains a
      therapeutic option and should not be withheld if GER is a reasonable suspect in
      asthma exacerbations. Although strong opinions have been voiced as to whether or
      not a good response to PPI therapy predicts a good response to antireflux
      surgery, the opinions, although logical, are based on personal experience and gut
      feelings; a good PPI response may not necessarily predict a good surgery
      response. Opinions suggesting that a poor response to PPI predicts a poor
      response to antireflux surgery also may seem logical but are not based on
      clinical data; a poor PPI response may not necessarily predict a poor antireflux
      surgery response. When the method is found that predicts which patients who have
      GER and asthma will respond to antireflux treatment, the results could be
      profound: fewer hospitalizations for respiratory complications, less pulmonary
      morbidity and mortality, less need for pulmonary medications, less time lost from
      work, fewer visits to physicians' offices, and less illness associated with
      corticosteroid therapy. For the present, however, clinical judgment and good
      sense still are our best friends. It is not unreasonable to urge patients to
      alter their lifestyle: the huge volume, calorie-dense, high-fat meals eaten
      before bedtime are not likely to prevent GER or add to their life expectancy.

PMID- 16104127
TI  - Current medical management of gastroesophageal reflux disease.
AB  - Gastroesophageal reflux symptoms are common. Not everyone who has heartburn has
      reflux, as some people have functional heartburn in addition to many other
      symptoms. Alternatively, not everybody who has reflux has heartburn, and many
      symptoms are identified in which reflux may be playing a role. In most cases, the
      initial management strategy is empiric medical therapy. Often, this brings
      symptom relief, but when it does not, alternative diagnoses need to be
      considered. High-dose treatment trials and ambulatory pH monitoring have become
      more important than endoscopy in the diagnosis of reflux. Patients who have
      reflux typically require a chronic disease approach. This can be with medical
      therapy, surgery, or endoscopic approaches. GERD is associated with decreased
      quality of life; however, given the many helpful treatment options, no one should
      suffer from the symptoms of GERD.

PMID- 16104128
TI  - New investigational therapies for gastroesophageal reflux disease.
AB  - Although PPI have revolutionized the treatment of GERD and its complications,
      many patients continue to have breakthrough symptoms and take antacids and H2RA.
      Furthermore, acid reflux actually is the innocent bystander, with few drugs
      available to target the true culprit, a dysfunctional LES. Future development of
      treatments, such as the GABA(B) agonists, which reduce TLESR, may prove an
      important advance in the therapy of GERD by controlling acid and nonacid reflux
      better. The chemical, pharmacodynamic, and clinical limitations of PPI may be
      addressed by the development of innovative drugs, such as the P-CAB or gastrin
      vaccine, to control acid secretion. Which of these drugs, if any, will be the new
      GERD drug for the millennium is unknown. There is no question, however, that
      improved drug treatments will parallel a better understanding of the complicated
      pathophysiology of GERD.

PMID- 16104129
TI  - Endoluminal gastroplasty: a new treatment for gastroesophageal reflux disease.
AB  - Initial studies demonstrate that EndoCinch is safe and may be an effective
      outpatient procedure. Symptom improvement, reduction in medication requirements,
      and ultrasound evidence of muscle hypertrophy are encouraging. The durability of
      these benefits remains in question. Seventeen percent of patients require a
      repeat gastroplication to achieve a satisfactory result and some elect to undergo
      laparoscopic Nissen fundoplication. Additional investigations are required to
      assess the number and location of the plications for optimal patient outcome.
      Prospective randomized studies comparing ELGP to medical and surgical treatments
      of GERD may be appropriate after device refinements. Of additional importance is
      the possibility of a cure with an ELGP. Patients who are self-medicated or
      noncompliant often are willing to seek consultation if a noninvasive curative
      procedure is available. One third of these patients have advanced disease and are
      treated best with surgery rather than an ELGP; thus, surgeons should be involved
      with ELGP for GERD control.

PMID- 16104130
TI  - Endoscopic antireflux therapy: the Stretta procedure.
AB  - The Stretta procedure is safe and effective for the treatment of GERD. There are
      well-documented clinical trial data supporting its use, including a randomized
      sham-controlled study, single- and multi-center prospective trials, and community
      practice reports. The complication rate is within the acceptable range for
      therapeutic endoscopic procedures and less than the published complication rate
      for laparoscopic fundoplication. The durability of effect also is established
      beyond 2 years in several studies. Stretta should be added to the GERD management
      algorithm specifically for patients considering an antireflux surgical procedure
      but who are not accepting of the risks of surgery and anesthesia. These patients
      typically present with incomplete GERD control, despite optimal antisecretory
      drug therapy, or intolerance to medical therapy. Stretta should be considered
      only for patients who fit the anatomic inclusion criteria, whereas antireflux
      surgery should be reserved for those who do not. The decision to undergo
      antireflux surgery or Stretta must be based on the relative risks and benefits of
      each procedure. Although antireflux surgery provides better control of esophageal
      acid exposure than Stretta, the outcomes for GERD symptoms, quality of life, and
      reduction in PPI use are comparable. Stretta has a low risk of acute adverse
      events, has no reported cases of long-term dysphagia, and obviates general
      anesthesia and hospitalization, whereas antireflux surgery has a reported adverse
      event rate of approximately 2%, a considerable incidence of dysphagia, and
      requires general anesthesia and 1 to 2 days in the hospital. Another advantage of
      the Stretta procedure is that antireflux surgery still can be performed in the
      case of failures. In conclusion, the Stretta procedure offers a minimally
      invasive, safe, and effective alternative to antireflux surgery for those
      patients who have GERD who are controlled unsatisfactorily on antisecretory
      medications, who are considering surgery, and who meet the anatomic criteria that
      make the procedure technically feasible and safe.

PMID- 16104131
TI  - Lower esophageal sphincter injections for the treatment of gastroesophageal
      reflux disease.
AB  - Endoscopic therapies for the control of GERD offer the potential for significant
      symptomatic improvement while obviating many of the potential drawbacks
      associated with long-term medical therapy with acid suppressive or neutralizing
      medications and traditional antireflux surgery. Such endoluminal therapies are
      intended to be safe with a brief learning curve, easily administered in an
      outpatient setting without the need for general anesthesia, reproducible, and
      durable. LES injection therapies share the common theoretic method of action of
      bulking at the GEJ, leading to loss of sphincter compliance and distensibility.
      In the case of Enteryx, this sustained effect has been demonstrated to be
      secondary to chronic inflammation, fibrosis, and encapsulation resulting from a
      foreign body response to the injectate. Available data suggest that a majority of
      patients respond to LES injection therapies, as demonstrated by a decreasing
      usage of PPIs after implantation, the ability of many patients to terminate PPI
      use completely, and improved GERD-HRQOL scores. Responses seem reasonably durable
      in follow-up assessment up to 24 months post treatment. Although there may be
      some placebo effect associated with treatment, patients injected with Enteryx
      respond better than a control group of sham-treated subjects. Individuals treated
      with LES injections, however, represent a select subgroup of the overall
      population of refluxers. Study subjects, by and large, have had uncomplicated
      GERD with typical reflux symptoms of heartburn or regurgitation that have
      responded to PPIs. Patients who have severe anatomic derangements, such as
      esophageal strictures, persistent esophagitis, Barrett's esophagus, or sizeable
      hiatal hernias, are excluded from clinical trials, as are patients who have
      severe motility disorders or significant comorbid conditions. Similarly, patients
      who have responded poorly to PPIs and those who have primarily extraesophageal
      manifestations of GERD have not been studied. Outcomes to date have been assessed
      over the short to medium term; long-term outcome studies are lacking. The
      durability of response, therefore, remains largely unknown, as does the incidence
      of any long-term complications or side effects. A postmarket study to assess the
      long-term safety and durability of Enteryx therapy up to 36 months is under way,
      as required by the FDA, with a target enrollment of 300 patients. Detailed cost
      analyses have yet to be reported. Such data are important not only for comparing
      the various endoluminal therapies but also for comparison to standard medical
      therapy and antireflux surgery. At present, no randomized trials are completed
      that compare injection therapies to other accepted treatments of GERD. The
      ability to perform fundoplication safely and effectively after failed LES
      injection therapy is not well known, in that the number of subsequent surgical
      cases is small and the results largely anecdotal to date. Likewise, the ability
      to use LES injection as salvage therapy after failed fundoplication has not been
      tested. The data regarding endoluminal injection therapies are similar to those
      after endoscopic plication and radiofrequency application to the LES, in that a
      definite symptomatic response is observed, but the objective documentation of
      diminished esophageal acid exposure lags behind. Esophageal acid exposure is
      normalized in a minority of treated subjects and improved in an additional
      subgroup, whereas the rate of symptomatic response exceeds these objective
      improvements. The reasons for this disconnect are the subject of much speculation
      and controversy. A placebo effect has been discussed, but clearly more factors
      are at play. Perhaps a study effect also is important, in that patients enrolled
      in clinical trials for GERD control may be more likely to modify their dietary
      and lifestyle habits in an effort to bring about symptom relief. Maybe the
      understanding of the perception of reflux events is lacking, and these
      endoluminal therapies work mainly by altering the perception of reflux more than
      the amount of reflux itself. A recent technologic review of injection therapies
      for GERD concludes that the "data for Enteryx are as compelling as those of any
      other open-label evaluation of an endoluminal therapy for GERD". There is much to
      be learned about all endoluminal techniques. For now, LES injections are
      promising therapies lacking supportive evidence of long-term safety and efficacy.
      The available data justify their use only in patients who have GERD symptoms
      responsive to PPIs and who do not have significant comorbidities or complications
      associated with GERD. Whether or not the role of LES injection techniques will be
      expanded to include more complicated cases, patients who are partially responsive
      to PPIs, combination therapy with other endoluminal techniques, or salvage
      therapy after failed fundoplication awaits further study.

PMID- 16104132
TI  - Antireflux surgery in the setting of lung transplantation: strategies for
      treating gastroesophageal reflux disease in a high-risk population.
AB  - In lung transplant recipients, GERD is associated with increased incidence of
      acute rejection, earlier onset of chronic rejection, and higher mortality.
      Surgical treatment of GERD in lung recipients seems to prevent early allograft
      dysfunction and improve overall survival. A total (360 degrees) fundoplication is
      shown to be a safe and effective method for treating GERD in lung transplant
      recipients and is the authors' procedure of choice, in most cases, for this high
      risk patient population. The principal goal should be to minimize reflux of
      enteric contents that may lead to micro- or macroaspiration events in this
      complicated group of patients. Perioperative care should involve a
      multidisciplinary approach, including physicians and other health care providers
      familiar with the complexities of lung transplant recipients.

PMID- 16104133
TI  - Surgical therapy for Barrett's esophagus.
AB  - Given the anatomic and functional defects almost universally present in patients
      who have BE, antireflux surgery is the most reliable means of stopping acid and
      nonacid (alkaline) reflux. Because patients who have BE have end-stage GERD, they
      require durable and reliable control of reflux, and the Hill procedure and
      partial fundoplication are associated with unacceptably high failure rates. In
      addition, there is mounting evidence that the success rates for Nissen
      fundoplication are lower in patients who have BE than in patients who have less
      severe GERD. Given that the most common mode of failure of a laparoscopic Nissen
      fundoplication is herniation of the fundoplication into the chest, patients who
      have BE must be considered at risk for having a short esophagus. The failure rate
      may be reduced by the liberal addition of a Collis gastroplasty, but the long
      term consequences of acid-secreting mucosa left above the fundoplication in
      patients who have BE remain unclear. Patients suspected of having a short
      esophagus on the basis of a large hiatal hernia, stricture, or long-segment BE
      should be considered for a transthoracic approach to their fundoplication, as
      this affords good esophageal mobilization and may obviate the need for a
      gastroplasty. Surgeons must pay particular attention to their own and published
      results and continue to refine the operation to maximize the likelihood of a good
      outcome in this difficult group of patients. It is only with excellent control of
      reflux that any differences in the risk of progression to dysplasia and cancer
      become apparent, and significant, between medically and surgically treated
      patients.

PMID- 16104134
TI  - Technical controversies in fundoplication surgery.
AB  - Gastroesophageal reflux disease (GERD) is a common health problem affecting more
      than 50% of the population. For those who experience more than occasional
      symptoms, GERD has a profound effect on their quality of life. With the advent of
      laparoscopic surgery, fundoplication has been used to treat GERD. Fundoplication
      also is used in the surgical management of paraesophageal hernias. Technical
      controversies are addressed in this article, including open versus laparoscopic
      approaches, the choice of complete (360 degres) or partial fundoplication,
      whether or not a gastroplasty is required, and the use of prosthetic materials in
      crural repair.

PMID- 16104135
TI  - CPOE has arrived. Will your institution lead, follow or just get out of the way?

PMID- 16104136
TI  - Partners in profits. Vendors, realizing they can't do it all, are partnering with
      other vendors.

PMID- 16104137
TI  - In your pocket. Small devices open up a wide world.

PMID- 16104138
TI  - A portal in a storm. My CARE source helps cancer patients weather the rough spots
      of treatment.

PMID- 16104139
TI  - Scaling the public health terrain. The trek is not over, but major hurdles have
      been overcome.

PMID- 16104140
TI  - Voice valuation. Use of a speech recognition ROI formula can show hospitals what
      to expect before they buy.

PMID- 16104141
TI  - When seconds count. EDIS radar screens show increased demand, integration and
      vendor consolidation.

PMID- 16104142
TI  - Side effects of tighter security. A serious case of password overload is solved
      with SSO.

PMID- 16104143
TI  - Mobile technology at work. Centralizing a mobile platform simplifies and enhances
      patient care.

PMID- 16104144
TI  - Securing the air. Wireless monitoring and protection can keep unauthorized users
      off the network.

PMID- 16104145
TI  - Performance reviews. Subjective assessment of the past gives way formance reviews
      because it allows to IT-facilitated guidance.

PMID- 16104146
TI  - [The interdisciplinary research of the life science and information technology].
AB  - This paper mainly discusses the interdisciplinary research of the life science
      and information technology, and also describes some research topics and
      direction, such as bioinformatics, biomedical optics, micro & nanotechnologies,
      bionics, etc.

PMID- 16104147
TI  - [The progress of electrical treatment of arrhythmia].
AB  - Described here is the progress of the electrical treatment for arrhythmia during
      the past half a century. The mechanism, their expression and the principles of
      electrical treatment for bradycardia, tachycardia and fatal arrhythmia-
      ventricular fibrillation (VF) are introduced respectively. The current situation
      and future development of the pacemaker, RF ablation and implantable
      cardioversion defibrillator are also discussed in the paper.

PMID- 16104148
TI  - [The research on linear control of pneumatic artificial muscles used in medical
      robots].
AB  - This paper presents the properties of Pneumatic artificial muscles and its
      application in medical robots. The linear model construction and minimum
      predictive error control algorithm for artificial muscles are discussed here too.
      This paper provides the experimental results of linear adaptive control, which
      show the control algorithm has certain applicable value.

PMID- 16104149
TI  - [A video communication system for telemedicine].
AB  - In this paper, point to point video communication system based on internet is
      deeply studied. Meanwhile the application system designed practically is
      introduced. It is emphasized that video compression coding based on low bit rate
      stream with ITU-T H. 263 agreement and related international standards is
      realized.

PMID- 16104150
TI  - [Research about the gray-level correction in DSA].
AB  - How to eliminate the background of other tissue and to protrude the blood vessel
      information is the basic requirements in DSA. Because of the complexity and non
      linearity of the X-ray imaging process, the common DSA technique cannot
      completely remove other tissue's image which lapped over the vessels. By
      experiments, this paper analyses and corrects the imaging process of the actual
      DSA system based on the "equivalent single energy" model, and the results
      indicate the validity of this method.

PMID- 16104151
TI  - [The automatic optimization arithmetic of selecting beam arcs in X-knife
      radiotherapy planning system].
AB  - In this paper, two new concepts of DR (Dose Repulsion) and DG (Dose Gravitation)
      are presented with their calculation formulas. For the problem of selecting beam
      arcs in x-knife radiotherapy Planning system, a mathematics model of constrained
      optimization has been built. Furthermore, we have produced a feasible project of
      automatic selecting optimized beam arcs plan using SA (Simulated Annealing)
      arithmetic based on the distribution of the fields of DR and DG in the reduced
      phase space.

PMID- 16104152
TI  - [Study on interventional ultrasonic thrombus ablation technique].
AB  - Ultrasonic thrombus ablation is a newly-developed technology for percutaneous
      arterial recanalization. An ultrasound angioplasty device is described here in
      detail. The device has an adjustable power output range and distal tip
      longitudinal displacement range. Experimental data suggest that this ultrasound
      device is significantly effective in ablating fresh thrombi.

PMID- 16104153
TI  - [The development of a polarized vernier optometer for tonic accommodation
      measurement].
AB  - A vernier optometer, based on the Scheiner principle, that makes use of polarized
      light, is designed and developed. It is specialized in measurement of tonic
      accommodation, accommodation and accommodation response. The vernier optometer
      has been proved by chinical testing results, to be a reliable and effective
      instrument with fine stabilily, good repeatability and sensitivity for short
      sight study relating to oculogyral parameters.

PMID- 16104154
TI  - [Design of print out function for a multi-parameter patient monitor].
AB  - This paper describes the design of the printing output function for a multi
      parameter patient monitor by using the graphic plot function of a Laser Printer.
      The ECG data are preprocessed with a notch filter and interpolation algorithm. A
      logical page is constructed in the extended memory for virtual page printing.
      This monitor is able to output a satisfied printing with ECG waveforms of high
      quality.

PMID- 16104155
TI  - [Clinical application and experimental studies of the pulsed inhaled nitric oxide
      flow controlling instrument].
AB  - A flow controlling system for pulsed inhaled nitric oxide has been developed and
      tested, and here its features and initial animal experiments and clinical
      applications are described. The physical characteristic test indicates that the
      practical released dose of NO gas is very close to the theoretical flow of NO gas
      at variant pressures. Animal experiments demonstrate that inhaled NO gas
      concentration is lower than the concentration of theoretical inhalation, but the
      variance is not remarkable (p>0.05). When sixteen cases with CHD and PH were
      chosen to inhale NO gas (15 ppm, 15 min) PAP and PVR of all cases were reduced
      after inhalation of NO gas from 617 +/-51.3 dyn x s x cm(-5), 54.4+/-13.1 mmHg to
      417+/-36.9 dym x s x cm(-5), 33.8+/-12.3 mmHg (PVR, p<0.01; PAP, p<0.01)
      respectively. When gas inhalation was stopped, these values returned to their
      base lines after a short period of time. All these show that the pulsed inhaled
      NO flow controlling instrument in accordance with the requirements of the
      designing, can be widely used in clinical diagnoses and treatments and will be a
      new tool offered for the treatments of the patients with PH.

PMID- 16104156
TI  - [Research and practice of a common model base on lab equipments computer
      interface].
AB  - The author provides a common receiving and processing model that suits for
      different kinds of lab equipment. Three years' practices of more than 100 lab
      equipments computer on-line operation show that this common model is reliable and
      feasible.

PMID- 16104157
TI  - [The development and clinical applications of automatic negative pressure gun for
      biopsy].
AB  - Using the new negative pressure biopsy technology, the automatic negative
      pressure gun and the specific puncture needle for the biopsy have been developed.
      Renal biopsies were conducted in 1136 cases, with the success rate being 99.9%,
      and 29 cases gross hematuria while the hepatic biopsies were conducted in 16
      cases, mass biopsies in 3 cases with the success rates being 100% respectively.
      The biopsy gun has the advantages of easy manipulation, higher success rate and
      lower incidence of complications.

PMID- 16104158
TI  - [Design and development of cerebrospinal fluid container].
AB  - The cerebrospinal fluid container is a device for storage of medicaments. By
      means of surgical operation, a ventricle catheter can be embedded in the
      ventricle of the brain. This safe and reliable device provides for neurosurgeons
      a new method of intracranical therapy and reestablishment of the circulating
      passage of the cerebrospinal fluid.

PMID- 16104159
TI  - [The surface treatment of artificial joint metal materials].
AB  - The surface treatment method for improving the functions of artificial joint
      metal materials and its properties have been sketched out in this paper. The
      purpose and the method of ceramic materials for coating and metal surface pre
      treatment are explained and we have also discussed the bioactive ceramic coating
      and its function.

PMID- 16104160
TI  - [The advances on the research of the body surface mapping].
AB  - Body surface mapping is introduced in this paper. The research of body surface
      mapping involves two main aspects: data acquiring system and data processing
      methods. The recommended design utilizes the virtual instruments concept and high
      speed open bus standard. The data processing methods involve qualitative and
      quantitative methods. Dynamic and static mapping techniques are introduced here
      as the qualitative methods while statistical methods, inverse calculation and
      principle component analysis are introduced as the quantitative methods.

PMID- 16104161
TI  - [The recent study and key technologies of an aided endoscopic surgical robot
      system].
AB  - This paper introduces the recent study and development of an aided endoscopic
      surgical robot system, and discusses its future trends--teleoperative robot
      system and telesurgery system. In addition, their key technologies are analyzed
      here in the paper.

PMID- 16104162
TI  - [Instrumentation and techniques in bone density measurement].
AB  - Manifold methods for bone mineral density analyses are introduced in this paper,
      and the characteristics of precision, accuracy, position, convenience,
      sensitivity and the radiation hazards of these methods are also discussed here.

PMID- 16104163
TI  - [The development of a detecting meter for pressure pain threshold].
AB  - A new instrument for measuring pressure pain strength to different bodily parts
      is introduced in this paper. For a new measuring appliance, it can be used
      conveniently for detection and evaluation of a patient's pressure pain threshold
      value, and for the research of bodily channels and network vessels. The system
      uses silicone oil as pressure conducting medium of a transducer, and five
      pressure detecting probes with different surface areas are designed to meet the
      requirements of the parts to be measured. The system has digital lock function
      for easy operation.

PMID- 16104164
TI  - [An assistant artificial hip joint].
AB  - The assistant artificial hip joint (AAHJ) is a new impermanent hip support
      implanted in the body. It is used for treatment of ischemic necrosis of the
      femoral head at the early stage. It reserves the natural femoral head, increases
      its containment and decreases its load, thus makes the recovery of the necrosed
      femoral head. The AAHJ's moving axis center is the same as that of the femoral
      head. Therefore, the moving range of the hip joint is very close to the normal
      postoperatively. The patient can walk with loading in 3 weeks after the surgical
      operation, and can regain his (or her) daily work and life in 2 to 3 months of
      the operation. The AAHJ's structure is simple and the price is cheap.

PMID- 16104165
TI  - [Virtual imagery in medicine].
AB  - The development of modern medical imaging and related technologies, and the
      increasing requirements for accuracy in clinical diagnosis and treatments give
      the emergence of a new discipline--virtual imagery in medicine. In this paper, we
      try to summarize its technical aspects, including virtual reality, 3-D image
      reconstruction and visualization, virtual endoscopy, and so on.

PMID- 16104166
TI  - [PACS evolution in China between 1990-2000 and its prospect].
AB  - In this paper a brief history of the development of PACS in China is reviewed,
      the current status of PACS is presented, and its development in the future is
      discussed.

PMID- 16104167
TI  - [The 3D PACS image system based on pipeline framework].
AB  - We put forward an image rendering system based on pipeline framework for
      processing and displaying medical images. Compared to original computer graphics
      algorithms divided into volume rendering and surface rendering, this framework
      can effectively comprehend methods of computer graphics and image processing,
      import some new concepts such as vertex buffer, pixel buffer and texture buffer.
      We implement Shaded Surface Display, Maximum Intensity Projection, Digitally
      Reconstructed Radiography, Multi planar Reformation, Curved Planar Reformation
      and Interactive Virtual Endoscopy in our new developed PACS image system.

PMID- 16104168
TI  - [Research on automated detection technology of standard 12 lead synchronous ECG
      signal].
AB  - The parts of system automatically detecting the standard 12-synchronous-lead ECG
      (electrocardiograms) signal based on personal computer is introduced in this
      paper. The object-oriented programming method is adopted based on Windows System.
      We put forward methods to analyze QRS complex wave, P wave, T wave and ST
      fragment. In this paper the techniques such as ECG signal preprocessing, cardio
      wave parameters detecting and wave pattern cognizing are discussed too.
      Furthermore we use wavelet transform technique to analyze the wave pattern and
      get sound effect.

PMID- 16104169
TI  - [The application of RTP protocol in multimedia telemedicine system].
AB  - This paper mainly describes the medicine multimedia communication techniques in
      some telemedicine systems, adapting the method of Real-time Transport Protocol.
      And the data dealt here include real-time consultation videos and ECG waveforms.

PMID- 16104170
TI  - [The computer aided-therapy system of tumor thermal-treatment instrument using
      HIFU technology].
AB  - Tumor thermal-treatment instrument is a newly developed medical instrument using
      HIFU technology. On the basis of a brief introduction of the system structure,
      this paper emphasizes the computer aided-therapy system applying a lot of
      computer technologies such as digital signal processing, digital signal
      communication computer aided design, artificial intelligence and database
      management system. Finally a concise therapy process using computer aided-therapy
      system is also introduced.

PMID- 16104171
TI  - [A fast technique for implementing data reduction].
AB  - A fast technique for implementing Holter cardio real time data reduction based on
      pointer and dual data buffers is presented in this paper, and an example of its
      application is also given here.

PMID- 16104172
TI  - [Development of the combined tumor therapeutic equipment].
AB  - This paper describes the development of the combined tumor therapeutic equipment
      based on the theory of 1 + 1 = 3 or 1 + 1 > 3 tumor combined treatment synergism.
      It has become a promising and valuable method dealing with cancer tumors for its
      good adaptability, better effectiveness and convenience. The therapeutic
      equipment is combined with PC and MS windows operation system, and adopts
      intellectual temperature control device, which realizes homogeneous and smooth
      heating to intracavity tumor focus and automatic processing and statistical
      management of all case data. The equipment works stably and is of great value in
      clinical applications.

PMID- 16104173
TI  - [The method and implementation of measuring the peak of bioelectrical signals].
AB  - It is always very difficult to process the bioelectrical signals, sampling,
      amplifying and quantifying because of the different sources it comes from and the
      mechanism it depends on. This paper mainly introduces a method of measuring the
      peak value of bioelectrical signals, expatiates on the structure, testing result,
      analysis for error and measure taken for improvement of the circuit designed by
      this method. At last, the paper also points out that the method is wonderful,
      simple, easy to carry out, and can be used in many medical systems.

PMID- 16104174
TI  - [The development of an automatic microscopic urinary sediment analyzer].
AB  - This paper introduces an automatic microscopic urinary sediment analyzer. A set
      of basic algorithms, including pretreatment and picking up characteristics is
      brought forward to realize the automatic segmentation of urinary sediment. This
      paper also characterizes the visible components in urinary sediment in morphology
      and has sum up 7 morphology parameters and a simple method of classification.

PMID- 16104175
TI  - [Quantitative analysis on pulmonary radiological images].
AB  - This paper presents a review of the quantitative analysis on pulmonary
      radiological images, including chest films and CT scans.

PMID- 16104176
TI  - [Fiber-optic biosensor].
AB  - Fiber-optic biosensor is now becoming a new research direction in biosensors. In
      recent 10 years it has got a compelling development and has been applied to
      medical pathogens, food toxicity, water pollution, biochemical weapons, fast
      detection for environmental samples, etc. In this paper its development is given
      out in detail.

PMID- 16104177
TI  - [The principle of extracorporeal shock wave lithotriptor and its locating
      system].
AB  - This article describes in detail the classification of extracorporeal shock wave
      lithotriptors, charging and discharging circuit of shock wave, wave source and
      the locating system of the lithotriptor, makes a comparison between three kinds
      of conventional shock wave sources, and analyzes the advantages and shortcomings
      of the different locating systems.

PMID- 16104178
TI  - [The scanning of "Chinese Journal of Medical Instrumentation" in recent years].
AB  - This paper analyzes the scientific research guidance, author's area & units
      distribution, coauthor rate and quotations in "Chinese Journal of Medical
      Instrumentation", and offers some suggestions for the Journal so as to play an
      important role in scientific research in the future.

PMID- 16104179
TI  - [Development of a multiple ligator and its endoscopic therapy for patients with
      esophageal varices].
AB  - The ligators we have developed is a kind of economical and effective six-ring
      ligator. Endoscopic variceal ligation (EVL) was performed to treat bleeding from
      esophageal varices in patients with liver cirrhosis using self-made ligator and
      foreign multiple ligator. There are similar effects with both self-made ligator
      and foreign mutiple ligator in the control of variceal bleeding, variceal
      obliteration and rebleeding (93.8%, 87.5%, 0 in the group with self-made ligator,
      94.5%, 87.1%, 2.4% in the group with foreign multiple ligator, P>0.05). In terms
      of the quality index, successful operation rate, hemastatic rate, variceal
      obliteration rate, rebleeding rate, complications and variceal recurrence rate,
      the self-made ligator is as good as the foreign multiple ligator, but much
      cheaper.

PMID- 16104180
TI  - [The development of FSCLZLY--an ascites-ultrafiltration instrument].
AB  - It's known to all that the refractory ascites treatment has so far been a very
      difficult clinical problem. We have extracted much experience from the practical
      techniques used in the refractory ascites treatments of more than 1,000 cases,
      and have developed the ascites ultrafiltration & concentration therapeutic
      instrument--FSCLZLY-A. The clinical applications show that it is very effective.
      Its effective rate is about 72.08%. Therefore, it is a very useful and important
      medical device for refractory ascites, for the improvement of renal function, and
      for the prevention of the infection of abdominal cavity.

PMID- 16104181
TI  - [The development of a treadmill system].
AB  - This paper introduces the designing concept of the ECG treadmill system and
      discusses the methods of its realization.

PMID- 16104182
TI  - [The development of a dispensing cabinet of total nutrient admixture].
AB  - A dispensing cabinet of total nutrient admixture is introduced in this paper.
      Which can be used for nutrient solution dispensing. The clinical application
      shows that it can provide a practical, simple, safe and satisfactory sterile
      environment.

PMID- 16104183
TI  - [A multi-functional drug-smearing and drug-injection instrument].
AB  - This paper instroduces the components and operating priciples of a multi
      functional drug smearing and drug injection instrument. The instrument has many
      advantages such as simple structure, convenient operation, no bacteria, drug
      saving, little pain and etc. All these advantages make it fit for medical
      applications.

PMID- 16104184
TI  - [Neurovisceral deposits with supranuclear ophthalmoplegia of vertical movements
      and presence in the bone marrow of blue histiocytes or Neville's disease. Report
      of two cases].

PMID- 16104185
TI  - [Recessive congenital methemoglobinemia. Clinical and laboratory study of one
      case].

PMID- 16104186
TI  - [Morquio's disease with delayed mucopolysacchariduria and leukocyte
      betagalactosidase deficiency].

PMID- 16104187
TI  - [Growth in height, bone and endocrine abnormalities in hypoplasia of the
      intrahepatic bile ducts. Eleven cases].

PMID- 16104188
TI  - [Salicylate poisoning in children].

PMID- 16104189
TI  - [Poliomyelitis in 1973-1974 in France].

PMID- 16104190
TI  - [Clear cell renal carcinoma in children. Study of two cases and review of the
      literature].

PMID- 16104191
TI  - [Pre, per and postoperative intensive care in thoracic sugery of the newborn].

PMID- 16104192
TI  - [Influence of protein and calorie malnutrition on infections. Results of a
      Senegalese hospital study].

PMID- 16104193
TI  - [Results of an enquiry on the tuberculin allergy rate in children ( 0-14 years].

PMID- 16104194
TI  - [Sedimentation rate greater than 100 mm in the early morning in children. Report
      of 100 consecutive cases].

PMID- 16104195
TI  - [For "psychological management" in juvenile rheumatoid arthritis].

PMID- 16104197
TI  - [Chronic juvenile rheumatoid arthritis in the hospital. Psychosociological study.
      II.--Hospitalization].

PMID- 16104198
TI  - [Chronic juvenile rheumatoid arthritis in the hospital. Psychosociological study.
      III--Interviews with the parents].

PMID- 16104199
TI  - [Chronic juvenile rheumatoid arthritis in the hospital. IV. Psychological study
      of affected children].

PMID- 16104200
TI  - [Chronic juvenile rheumatoid arthritis in the hospital. V.-- Schooling, social
      and family life].

PMID- 16104201
TI  - [Postnatal development of the human lung: its relationship with pulmonary
      function and respiratory pathology].

PMID- 16104202
TI  - [The syndrome of peripheral systemic atelectasis in children. (Report of twelve
      cases)].

PMID- 16104203
TI  - [Recurrent aspiration pneumonia due to a neuromuscular deficiency of the bucco
      pharyngeal structures. Description and results of a new method of investigation
      by electromyographic techniques].

PMID- 16104204
TI  - [Current aspects of the diagnosis and treatment of purulent pleurisy in
      children].

PMID- 16104205
TI  - [Study in pediatrics of an anxiolytic drug: clobazam].

PMID- 16104206
TI  - [Techniques of neonatal medicine and arthritis of the hip].

PMID- 16104207
TI  - [A simplified method of assessment of unconjugated bilirubin in small birth
      weight newborns].

PMID- 16104208
TI  - [Leukocytosis and polynucleosis in non-infected newborns with low birth weight].

PMID- 16104209
TI  - [Gastric miliary ulcer in the newborn].

PMID- 16104210
TI  - [Consequences of phosphorus intake on phosphorus and calcium metabolism in small
      birth weight newborns].

PMID- 16104211
TI  - [Galactokinase deficiency].

PMID- 16104212
TI  - [Study of 216 cases of tuberculous meningitis in children].

PMID- 16104213
TI  - [Phototherapy: blue or white?].

PMID- 16104214
TI  - [Acute respiratory distress and bacterial infection in premature infants during
      the first 24 hours of life].

PMID- 16104215
TI  - [Cutaneo-mucous hyalinosis or Urbach-Wiethe's disease in children. Report of one
      case followed for fourteen years].

PMID- 16104216
TI  - [Pyloric atresia. A little known medical and surgical emergency in the newborn].

PMID- 16104217
TI  - [Gastric pneumatosis in the new-born. A rare localization of digestive
      pneumatosis. Report of two cases].

PMID- 16104218
TI  - [Polysplenism, levo-isomerism and atresia of the bile ducts].

PMID- 16104219
TI  - [Postnatal sub-epicranial hydroma].

PMID- 16104220
TI  - [Acrocephalosyndactylia and female pseudo-hermaphroditism and hypertensive
      nephropathy].

PMID- 16104221
TI  - [Poland's syndrome. Report of 20 cases].

PMID- 16104222
TI  - [Tobramycin in pediatrics. Report of 24 cases].

PMID- 16104223
TI  - [The course of serum immunoglobulin levels during the first month of life].

PMID- 16104224
TI  - [Crohn's disease in children. Report of eleven cases].

PMID- 16104225
TI  - [Agenesis and hypoplasia of the pulmonary artery. (Clinical, radiological and
      embryological study of two cases)].

PMID- 16104226
TI  - [Course and treatment of 205 cases of bacterial meningitis].

PMID- 16104227
TI  - [Spontaneous subcutaneous mediastinal emphysema in children].

PMID- 16104228
TI  - [Clinical and biological study of the very early forms of juvenile rheumatoid
      arthritis].

PMID- 16104229
TI  - [A new case of vaginal endodermal sinus tumor in an infant].

PMID- 16104230
TI  - [Cutis marmorata telangiectica congenita. Clinical, pathological and
      ultrastructural study of two cases].

PMID- 16104231
TI  - [Complications of B.C.G. vaccination].

PMID- 16104232
TI  - [Tracheal intubation in the treatment of acute laryngitis in children].

PMID- 16104233
TI  - [Atresia of the small intestine, cystic fibrosis and septicemia due to Candida
      albicans in a newborn].

PMID- 16104234
TI  - [Disorders of hemostasis and respiratory distress in the newborn. Hyaline
      membrane disease and transient respiratory distress].

PMID- 16104235
TI  - [Thrombosis of the renal veins in a premature infant. Treatment with heparin and
      urokinase].

PMID- 16104236
TI  - [Prenatal obstruction of the left hypogastric artery].

PMID- 16104237
TI  - [Rubella vaccination program in Brittany (1971-1975)].

PMID- 16104238
TI  - [Pre and post-vaccinal rubella seroepidemiology in Brittany (1971-1975).
      Comparative study of Cendehill and Plotkin's strains].

PMID- 16104239
TI  - [Idiopathic dilatation of the right atrium manifested in infancy by arrhythmia].

PMID- 16104240
TI  - [Three cases of right-sided diaphragmatic hernia associated with abnormal
      position and morphology of the liver].

PMID- 16104241
TI  - [Lumbo-sacral spondylolysis and spondylolisthesis in children. Study of 82
      cases].

PMID- 16104242
TI  - [Correction of hypoproteinemia in premature and full-term new born infants].

PMID- 16104243
TI  - [W-shaped diaper rash in infants].

PMID- 16104244
TI  - [Tuberculosis of young children with sensory changes. (Report of two cases)].

PMID- 16104245
TI  - [Macroscopic hematuria in infants and children. Report of 103 cases].

PMID- 16104246
TI  - [Osteopetrosis in infants. Report of two cases with a study of phosphorus and
      calcium metabolism].

PMID- 16104247
TI  - [Congenital disorder of thyroid hormonegenesis with abnormal synthesis of
      iodohistidines].

PMID- 16104248
TI  - [Severe infectious mononucleosis and reticulosarcoma].

PMID- 16104249
TI  - [Elfin facies, mental retardation and cardiovascular anomalies (Williams and
      Beuren's syndrome). Report of two cases].

PMID- 16104250
TI  - [Respiratory infections due to Mycoplasma pneumoniae].

PMID- 16104251
TI  - [Psychological development and cystic fibrosis].

PMID- 16104252
TI  - [Study of colonisation by resistant enterobacteriaceae in premature newborn:
      comparison with children not receiving antibiotics and children treated with
      ampicillin].

PMID- 16104253
TI  - ["Septum transversum" syndrome. Diverticulum of the left ventricle. Report of one
      case].

PMID- 16104254
TI  - [Congenital amegakaryocytic thrombopenia with radial aplasia].

PMID- 16104255
TI  - [Technique of high intensity focused ultrasound for tumor therapy].
AB  - HIFU technique has been applied in clinic tumor therapy for over ten years. It is
      the important indication of a new development stage of the ultrasound in
      medicine. In the paper, the present status of HIFU for tumor treatment is
      introduced and its future development is discussed too.

PMID- 16104256
TI  - [The multi-resolution image registration algorithm for digital subtraction
      angiography].
AB  - The proposed registration algorithm based on wavelet transform is a multi
      resolution block matching one, which exploits the hierarchical self-similarity of
      Digital Subtraction Angiography images. This method befittingly trades off
      between the estimation precision and computational complexity, because the
      registration precision is from coarse to fine, which reduces the searching
      complexity of motion vector. This technique has been proved that the convergence
      speed is exponential. The proposed method takes full advantage of the precise
      location both temporally and frequently which characterizes the wavelet
      transform. Both the matching speed and consistency are boosted without the loss
      of matching performance.

PMID- 16104257
TI  - [A new program-controlled telemetry technology for pacemakers].
AB  - This thesis is about a new technology of program-controlled telemetry for
      pacemakers. The system utilizes digital logic circuit design, and the program
      controlled part uses single chip to control for display and debug. PWM and
      reflectance telemetry may improve the preciseness and correctness of signal
      transmission, and reduce the power consumption of pacemakers and prolong the
      lifetime.

PMID- 16104258
TI  - [Design of portable biomedical information detecting instruments].
AB  - The article discusses how to design a portable instrument to detect the
      biomedical information in five aspects, such as signal catching, MPU selecting,
      anti-interference, power controlling and portability. It gives some ideas to
      solve the problems in instrument designing.

PMID- 16104259
TI  - [Development of HPC-based monitoring devices for community medicine].
AB  - This paper introduces several novel HPC-based monitoring devices for community
      medicine. They support net transmission and have superiorities of portability,
      small size, good mobility, easy use and strong adaptivity.

PMID- 16104260
TI  - [A vest-pocket instrument for the detection and treatment of the onset of
      epileptic seizures].
AB  - A new vest pocket medical instrument is here presented. It can automatically
      detect and identify the signals of the onset of epileptic seizures, and then as
      necessasy, will automatically generate an acoustic stimulation that may weaken
      and shorten the epileptic activity at the initial stage.

PMID- 16104261
TI  - [Research of high precision of temperature measurement in microwave hyperthermia
      therapy].
AB  - This paper describes a new method of temperature measurement in microwave field.
      This method resolves a series of problems such as the microwave field
      suppression, the linearization of the temperature sensor and the sensor
      exchangeability.

PMID- 16104262
TI  - [Function of single channel electrocardiograph is expanded in community medical
      service].
AB  - The paper introduces a designing idea and a carrying-out scheme about expanding
      functions of single channel electrocardiograph in Chinese community medical
      service and looks forward to its applying prospects.

PMID- 16104263
TI  - [An experimental study of immune function effect of rats irradiated with the
      complex field cure instrument].
AB  - The complex field cure instrument is a new medical instrument with which an
      experiment was carried out. Rats were continuously irradiated by the complex
      field for 90 days, with a day's total dose of 285.9 M.T.G. while other rats
      weren't irradiated for control group. The animals were respectively killed at 7d,
      14d, 30d, 60d and 90d, and their blood samples were taken for cell and humoral
      immune analysis. The results show that values of lymphocyte transform rate,
      soluble receptor (SIL-2R), total hemolytic complement levels (CH50) and
      immunoglobulin (A.G.) after irradiation are more than those of the control group
      having proved that the instrument may improve immune function of rats.

PMID- 16104264
TI  - [The study of human brain soft-tissue deformations based on the finite element
      method].
AB  - This paper presents the recent progress of the study of human brain soft-tissue
      deformations based on finite element method. Some possible problems and issues
      about the implementation of the methods are also discussed.

PMID- 16104265
TI  - [Micro-fabrication technology in biomedical applications].
AB  - In this paper we briefly introduce some microdevices which have been developed
      recently for biomedical applications by micro-fabrication technology. These
      applications mainly include areas of diagnostics, drug delivery, tissue
      engineering and minimally-invasive surgery.

PMID- 16104266
TI  - [DICOM in radiotherapy].
AB  - Digital Image Communication in Medicine (DICOM) defines a standard method to
      store and transmit digital medical image information, in which there is a piece
      of implemented protocol named DICOM-RT that specially addresses both the
      transmission of radiation therapy image data and the ancillary data. In this
      paper, we firstly introduce the DICOM-RT with the emphases on its components,
      relationship with radiotherapy and how to produce the DICOM-RT object that refer
      to some certain radiotherapy information. Then we expatiate on the impact that
      benefits from applying DICOM-RT to radiotherapy, with an aid to accelerate its
      application in China.

PMID- 16104267
TI  - [A study on medical image fusion].
AB  - Five algorithms with its advantages and disadvantage for medical image fusion are
      analyzed. Four kinds of quantitative evaluation criteria for the quality of image
      fusion algorithms are proposed and these will give us some guidance for future
      research.

PMID- 16104268
TI  - [Bibliometric analysis of scientific papers of "Chinese Journal of Medical
      Instrumentation" from 1997 to 2001].
AB  - The scientific papers in "Chinese Journal of Medical Instrumentation" from 1997
      to 2001 have been analysed by bibliometrics, including the characteristics of the
      periodical, its author's areas, units distribution and quotations. Some
      suggestions have been put forward to promote the biomedical engineering research.

PMID- 16104269
TI  - [The latest development of MRI equipment].
AB  - This paper describes briefly the latest development of MRI equipment and its
      masket.

PMID- 16104270
TI  - [The medical gas central supply system and its quality control].
AB  - This paper introduces the principles of the medical gas central supply system and
      its structure, Classification, standards, flow chart and its advantages, and its
      quantity guarantee and quality control.

PMID- 16104271
TI  - [A conjecture about Jingluo and suggestions on its research].
AB  - The Jingluo is a great hypothesis and theory of Chinese traditional medicine. The
      physical existence of Jingluo phenomena has been proved by many medical
      practices, but its real mechanism is still unknown. Here is a conjecture about
      Jingluo: "The essence of Jingluo is in CNS, the lines of Jingluo on soma is only
      actually a mapping of some strong connection networks in cortex or white matter
      of brain". Many new modalities of medical imaging like fMRI, PET, SPECT and
      Mapping MEG can do a good job on functional brain imaging. If we improve their
      spatial resolution and develop new methods to indicate brain activities, maybe we
      can unveil the secret of Jingluo.

PMID- 16104272
TI  - [Development of the chip system for measurement of red blood cell rheology].
AB  - We have developed a novel silicon microchannel system for the research of the red
      blood cell rheology and deformation. Recurring to many kinds of information
      technologies and advanced test means such as the electronic microscope, the image
      acquisition system and the computer processing system and by using the up-to-date
      Micro Electro Mechanical System (MEMS) technology, a new measuring system of red
      bood cell deformation is designed based on the chip and a model using the silicon
      microchannel to simulate capillary vessel network. It provides a real-time
      collection and anaysis of data which include image, speed, flow parameter, and so
      on. It provides printing, storage of the analysis results and patients' database
      management.

PMID- 16104273
TI  - [The design of a cardiac monitoring and analysing system with low power
      consumption].
AB  - The paper deals with a portable analyzing monitor system with liquid crystal
      display (LCD), which is low in power consumption and suitable for China's
      specific conditions. Apart from the development of the overall scheme of the
      system, the paper introduces the design of the hardware and the software. The
      80196 single chip microcomputer is used as the central microprocessor to process
      and real-time electrocardiac signal data. The system have the following
      functions: five types of arrhythmia analysis, alarm, freeze, and record of
      automatic paperfeeding. The portable system can be operated by alternate-current
      (AC) or direct-current (DC). Its hardware circuit is simplified and its software
      structure is optimized. Multiple low power consumption and LCD unit are adopted
      in its modular designs.

PMID- 16104274
TI  - [Design of double ultrasound pulse transmitting and receiving circuits used in
      ultrasound thermometry].
AB  - This paper introduces double ultrasound pulse transmitting and receiving circuits
      used in ultrasound thermometry. Using the circuits, double ultrasound pulses
      could be made synchronously to satisfy the requirements of ultrasound
      thermometry, and the weak ultrasound echo signals are received successfully. The
      crux experiment waveform offered shows that the circuits have high reliability.

PMID- 16104275
TI  - [A 3D-rendering system for medical images based on COM].
AB  - This paper introduces a 3D medical image rendering system. The system uses the
      technology of COM with a fine upgradable and maintainable performances. Its main
      functions include image filtering, enhancement, image classification &
      segmentation, image registration, image interpolation and 3D display. The system
      can run on PC, so it owns a good practical value.

PMID- 16104276
TI  - [The development of a blood pressure monitor based on oscillometric method].
AB  - This paper describes a type of blood pressure monitor we have developed using
      8031 chip microprocessor based on oscillometric method and the designs of
      hardware and software. Comparing the measurement results of oscillometric method
      with that of direct invasive measurement method, we find that the monitor is very
      useful in clinical applications. Finally in the paper, some improvements that can
      be made in the monitor are proposed.

PMID- 16104277
TI  - [A multifrequency phase-controlled driving system for ultrasound therapy].
AB  - Ultrasound therapy is a new type of therapy technology, there are hyperthermia
      and high intensity focused ultrasound surgery (HIFUS). Compared with a single
      frequency system, mutiple frequency system has an additional function to combine
      power patterns of different frequencies. This function increases the availability
      of power patterns to treat tumors of various shapes and depths. Therefore, we
      have in this article proposed a system with the ability to drive ultrasonic
      phased arrays of multiple resonant frequencies for ultrasound hyperthermia and
      HIFUS. The results show that this system is able to (1) drive multi-element
      applicators or phased arrays of a single resonant frequency through the
      multichannel power amplifiers, (2) concurrently drive transducer with different
      resonant frequencies, (3) adjust the relative phase and output power of each
      channel for the scanning ultrasonic focus, and (4) operate each channel with good
      output stability.

PMID- 16104278
TI  - [Development of an analysis system for X-ray cephalometry by Windows platform].
AB  - Here in this paper introduced is an analysis system for X-ray cephalometry
      developed through Windows platform,which includes three parts: data input,
      cephalometry analysis & calculation, and display & printing of diagnostic
      results. It has been applied in orthodontic department of Stomatological Hospital
      of the Fourth Military Medical University, and it is quite convenient for
      doctors' cephalometry diagnosis.

PMID- 16104279
TI  - [Design of automatic monitoring for hyperbaric oxygen-cabins by using
      microcomputer].
AB  - This paper introduces a kind of union of hyperbaric oxygen-cabins and a
      microcomputer through which, the temperature measurement, the monitoring of
      oxygen concentration and air exchange are realized automatically with uniformly
      ascending voltage and static constant voltage.

PMID- 16104280
TI  - [The design of precision measure circuit for frequency & duty cycle of
      bioelectrical signal and its application in neuron-threshold stimulator].
AB  - This paper mainly introduces the principles of a type of circuit for measuring
      frequency & duty cycle of low-frequency signals, and its applications in neuron
      threshold stimulator. The circuit has the advantages of simple structure and
      accurate measurement.

PMID- 16104281
TI  - [The development of the preamplifier for the microcomputer-detecting system of 3
      channel ECG signals].
AB  - This paper introduces the preamplifier for the microcomputer-detecting system of
      3-Channel ECG signals and its technical specifications. The practical experiments
      and clinical applications show that its performances conforms with all the
      requirements of the system.

PMID- 16104282
TI  - [The design and implementation of DICOM Server Mediate Layer].
AB  - A DICOM Server Mediate Layer is introduced in this paper. It communicates with
      modalities according to DICOM3.0 standard on the one hand, provides a simple way
      to interface with other application on the other hand, this mades the
      implementation of DICOM service much easier for other applications.

PMID- 16104283
TI  - [Development and clinical application of the tractor for the fracture reduction].
AB  - This paper expounds how the tractor for the fracture reduction works. The
      clinical results show that the traction apparatus is a labour-saving and time
      saving orthopedic device with simple operation and few suffering to patients.

PMID- 16104284
TI  - [Development of the new measuring & training device for eustachian tube opening
      function].
AB  - This paper presents to you the principles, composition, features and applications
      of ET-100 measuring-training device for eustachian tube opening function.

PMID- 16104285
TI  - [Study of the marker for a neuronavigation system].
AB  - With different ratios, Omnipague mixed with cod liver oil and Meglumine
      Diatrizoate mixed with cod liver oil are compared with the stardard marker under
      the scanning of CT and MR in order to find the better ratio and materials for the
      marker. The experimental results show that the performances of both Omnipague
      mixed with cod liver oil and Meglumine Diatrizoate mixed with cod liver oil are
      better than the stardard marker. CONCLUSION: Omnipague mixed with cod liver oil
      and Meglumine Diatrizoate mixed with cod liver oil can be used in making marker
      for neuronavigation system.

PMID- 16104286
TI  - [Development and application of ultrasound technology for hyperthermia].
AB  - It has been a long time since ultrasound hyperthermia began to be used in the
      clinical management of cancers and benign diseases. Numerous biological and
      clinical investigations have demonstrated that: hyperthermia in the range of 41
      45 degrees C can significantly enhance clinical response to radiation therapy and
      chemotherapy, and high-temperature hyperthermia (greater than 65 degrees C) alone
      is now being used as an alternative to conventional invasive surgery for
      selective tissue destruction, causing tumor coagulation and necrosis. As a
      promising noninvasive and effective local therapy, HIFU has attracted great
      attention. China is advanced in the clinical applications of HIFU. This article
      gives an introduction of the development and applications of ultrasound
      hyperthermia technology, and also provides a general review of a selection of
      ultrasound hyperthermia systems both in clinical use and under development.

PMID- 16104287
TI  - [The developing trend of the clinical laboratory].
AB  - The clinical laboratory technology has gradually changed the traditional
      detection methods. The new detection technology provides a more rapid and more
      accurate way for the disease diagnosis. The designs of the clinical laboratory
      equipments pay more attention to human factors, low cost and benefit for
      environment protection.

PMID- 16104288
TI  - [Telemedicine and telecommunication vehicle].
AB  - This paper introduces remote Computed Tomography van, telemedicine and
      telecommunication vehicle.

PMID- 16104289
TI  - [The invention and application of the vaginal suturing-aid apparatus].
AB  - We have invented a barrel-shape suturing-aid apparatus with a light source on one
      side and a trapzoid cranny for suturing on the other side. There are many
      advantages proved by clinical practices in applying the suturing-aid apparatus:
      1. to increase the suturing speed and relieve the pains of patients; 2. to avoid
      the infection of HBV by blood and crossinfection; 3. to improve the illumination
      condition and avoid no suturing of the hurt tissue.

PMID- 16104290
TI  - [Percutaneous visceral tumor puncture director].
AB  - A percutaneous visceral tumor puncture director is introduced in this paper,
      which can be used for needle biopsy and brush biopsy in kinds of visceral tumor.
      The clinical informations show that the application of the director can increase
      the positive ratio of puncture, and it has important clinical value. The director
      is safe, practical and easy to operate.

PMID- 16104291
TI  - [APV--a new mode of mechanical ventilation].
AB  - This paper introduces the adjusting principles of APV mechanical ventilation.

PMID- 16104292
TI  - [A comparison of the performances between the ionization chamber dosimeters used
      in radiation therapy].
AB  - The structural principles and technical performances of different ionization
      chamber dosimeters used in radiotherapy have been briefly introduced in this
      paper. In the mean time, a comparison of technical performances of four different
      kinds of ionization chamber dosimeter used in hospitals in China has also been
      made. The data show their quality meet the required specification specified by
      IEC731 and JJG912-96, so they can be used as field survey dosimeters in
      hospitals. Some precautions in using these dosimeters are given here too.

PMID- 16104293
TI  - [Application of digital signal processing to the analysis of biomolecular
      sequences].
AB  - A preliminary introduction is given to the application of digital signal
      processing to the analysis of biomolecular sequences. How to transform a
      character string into a numerical sequence is discussed from the time domain and
      the frequency domain.

PMID- 16104294
TI  - [The developments of medical monitoring techniques].
AB  - Based on analyzing the problems of the existing medical monitoring systems and
      the clinical needs in medicine the main development aspects of modern medical
      monitoring techniques are discussed in the paper. Then the urgent needs of
      monitoring techniques are presented here.

PMID- 16104295
TI  - [A digital tongue image analysis instrument for Traditional Chinese Medicine].
AB  - A digital tongue image analysis instrument (TIAI) based on computer for
      Traditional Chinese Medicine is introduced. Some of the key techniques, including
      the image acquiring condition and method, the evaluation of tongue characters,
      and the management of tongue image data, are discussed as well. TIAI can provide
      a non-invasive, quantitative, and objective analysis approach and enhance the
      theory level and practical ability of the Traditional Chinese tongue diagnosis.

PMID- 16104296
TI  - [The development of 3D US system for treating target localization in focused
      ultrasound surgery].
AB  - Focused Ultrasound Surgery (FUS) is a promising minimally invasive technique in
      tissue ablation. Because of the high intensity at the ultrasound focus, a precise
      3D-localization system is required to determine the site of the treating target
      in order to increase the efficiency and security of FUS. This paper represents a
      three dimensional ultrasound (3D US) localization system developed and its
      workflow. The system is mainly composed of imaging and image processing system,
      movement device and its controlling circuits, and position feedback device. The
      system has a maximum scan range of +/- 30 degrees with a resolution of 8 levels
      from 0.54' to 0.36 degrees. For a spherical shape like target, in theory, the
      maximum diameter is 160 mm the system can treat. The system can be used to
      localize precisely the treatment targets with general sizes in the suitable parts
      of the body in FUS.

PMID- 16104297
TI  - [Research on the hyperthermia-therapy performances of invasive microwave
      antennas].
AB  - The paper introduces four kinds of 2450 MHz antennas including noninsulted
      (bare), insulated-open-tip (I.O.T.), dipole-type and sleeve invasive microwave
      ones. The comparison between the antennas' hyperthermia performances in the
      muscle tissue phantom made by specific absorption rate (SAR) shows that the
      sleeve antenna is the best. It has a bigger heating range and a changeless shape
      and is independent of the inserting depth.

PMID- 16104298
TI  - [Sensing scheme of minim liquid density based on Lamb-wave].
AB  - This paper presents and discusses the liquid density sensing potential of a delay
      line Lamb-wave sensor configuration, where Lamb wave is excited only by
      interdigital transducer (IDT), without membrane when fabricated. An optimized cut
      orientation and the normalized thickness of substrate by using genetic algorithm
      is presented to improve the sensitivity of the sensor and to get low noise.
      Experimental measurements performed on Lamb-wave device fabricated from Y-Z
      LiNbO3 in a delay line configuration are found to be in agreement with
      theoretical calculations.

PMID- 16104299
TI  - [The collecting and processing system of the sound signal of larynx].
AB  - This paper presents a new kind of collecting and processing system of the sound
      signal of larynx where double sound cards and software filter are used. The
      installation of the double sound cards and processing proposal of software are
      mainly discussed and a new kind of ADC method of dual-channel sound signal is put
      forward in this paper. This system has the feature of reliable performance,
      simple installation and easy maintenance.

PMID- 16104300
TI  - [Automatic ECG analysis system based on TMS320F206].
AB  - An automatic ECG analysis system based on DSP is introduced in this paper. It can
      fulfill the functions of signal regulation, adaptive filtering, QRS waves
      positioning, and automatically recognize more than 10 kinds of arrhythmia and
      report alarm. TI DSP product--TMS320F206 is applied in this system to accomplish
      the adaptive filtering and automatic diagnosis of arrhythmia for the need of real
      time signal processing.

PMID- 16104301
TI  - [A novel miniature robotic endoscope design for intestinal inspection].
AB  - This paper makes a comparison between the traditional endoscope system and the
      active robotic endoscope system, discusses the human intestine-working conditions
      of the robotic endoscope system in detail and its design requirements. An active
      robotic endoscope system based on earthworn-locomotion principles is proposed
      here and besides, its structure and locomotion mechanism are analyzed. A new
      method of human intestinal intervention is brought out and it can prevent the
      robotic endoscope guided by a cone-shaped guide pipe from being jammed or
      damaged.

PMID- 16104302
TI  - [The design for curing circuit used in Chinese acupuncture & moxibustion
      instrument].
AB  - In this paper, we introduce a multiple electro-stimulative pulse generator based
      on IC555, which can produce continuous, discontinuous, frequency modulated and
      amplitude modulated modes, and thus multiple-output, independent adjustment &
      control are realized. The principle block diagram and a reference circuit are
      presented too. This design adds acusetor curing function to BME-500 series
      Chinese Acupuncture & Moxibustion Instrument, making it a multifunctional therapy
      device of electro-acupuncture, massage and drug permeation Moxibustion
      Instrument.

PMID- 16104303
TI  - [The assessing tools of the treatment planning in X-knife].
AB  - The treatment planning can directly decide the treatment effect of X-knife. This
      paper presents some qualitative and quantitative tools assessing the treatment
      planning, mainly they are the isodose curve, dose-wash, volume dose and dose
      volume histogram.

PMID- 16104304
TI  - [Design and clinical application of a three-dimensional biomechanical traction
      appliance for protrusion of intervertebral disc].
AB  - A three-dimensional biomechanical tracting appliance is introduced in the
      article, which is used to treat the protrusion of intervertebral disc. The
      appliance is light, practical, adjustable 3D biomechanic, simple and with
      multiple functions and convenient operation.

PMID- 16104305
TI  - [Development and clinical application of the EMG information management system].
AB  - This paper introduces an EMG multi-gateway analysis diagnosis and information
      management system. The clinical applications show that this system has higher
      efficiency and standard report contents, and easy statistical analysis. And it
      also offers EMG standard figure, normal value data, nerve and muscle select
      scheme etc, for reference.

PMID- 16104306
TI  - [A practical system for B-mode ultrasound image acquisition and patient's medical
      history management].
AB  - A practical system of B-ultrasonic is here introduced. By a special medical video
      card, the video image is digitized and captured dynamically or statically into
      computer. This system realizes a variety of functions such as the B-ultrasonic
      video image's acquisition and display, as well as the editing, processing,
      managing, storage, printing, It can build the database of patient's case history
      automatically. Together with other medical image workstation the system can be
      built as a PACS system of the hospital. And it can also act as an independent
      system.

PMID- 16104307
TI  - [Review: Segmentation and classification methods of 3D medical images].
AB  - This paper presents a survey of recent publications (published in 1990 or later)
      concerning segmentation and classification of medical images. These methods will
      be classified into six types: cluster (threshold), statistics methods, deformable
      contour, region growing, mathematics morphology, nonlinear methods (fuzzy
      segmentation, neural networks, genetic algorithm) and 3D model. Each of the major
      classes of image segmentation and classification techniques and several specific
      examples of each class of algorithm are described respectively in detail. At
      last, the developing trend of 3D medical image is also discussed.

PMID- 16104308
TI  - [Comparison of image acquiring methods in PACS].
AB  - We discuss in this paper some kinds of image acquiring methods, particularly
      under the current domestic hospital environment.

PMID- 16104309
TI  - [A discussion on neonate mechanical ventilation].
AB  - Based on the unique situation pertaining neonatal mechanical ventilation, this
      paper discusses the technical requirements for ventilating neonates effectively
      and lung-protectively. An available good technical solution is put forward.
      Besides, it is also discussed what should be taken care of when ventilating
      neonates.

PMID- 16104310
TI  - [The present status and development of biotelemetry].
AB  - Telemetering is one of the ideal methods of metering biomedical signal. This
      paper emphasizes remote medical treatment system and its exploitation,
      realization and application. It gives an overview of the recent development of
      biotelemetry. At the same time, it discusses the principle, realization, new
      development of other biotelemetry methods and further research tendencies on
      biotelemetry as well.

PMID- 16104311
TI  - [The format converting from MR images into BMP ones].
AB  - This paper is to introduce the method in which the SIEMENS' MR images are
      converted into BMP format ones based on the correct format analysis of SIMENS' MR
      images, we condude that the conversion from SIEMENS' MR image to BMP image can be
      realized by software design.

PMID- 16104312
TI  - [Advances in medical ultrasonic instrumentation].
AB  - Recent advances in medical ultrasonic instrumentation are introduced in this
      review, including the progresses in transducer, diagnostic and therapeutic
      applications. Future development is also discussed.

PMID- 16104313
TI  - [The automatic iris map overlap technology in computer-aided iridiagnosis].
AB  - In the paper, iridology and computer-aided iridiagnosis technologies are briefly
      introduced and the extraction method of the collarette contour is then
      investigated. The iris map can be overlapped on the original iris image based on
      collarette contour extraction. The research on collarette contour extraction and
      iris map overlap is of great importance to computer-aided iridiagnosis
      technologies.

PMID- 16104314
TI  - [CT/MRI-based software for 3-D brachytherapy planning system].
AB  - The paper presents a 3D Brachytherapy Planning System based on CT/MRI images.
      Unlike other percutaneous radiotherapy planning systems, it provides doctors with
      an interactive source layout function, including accurate and quick dosage
      distribution calculation and dynamical 2D/3D display. A special template library
      and an integrated planning evaluation/alert subsystem are incorporated in the
      system. The system successfully has many functions such as data acquisition,
      registration, segmentation, image processing, 3D reconstruction and planning
      report output. Various automated procedures, 3-D graphics and a user-friendly
      interface GUI enable the system to be a powerful and practical one meeting well
      the chinical therapeutic demands.

PMID- 16104315
TI  - [Analysis of the automatic brightness controlling for x-ray imaging systems].
AB  - In this paper, the question about automatic brightness control for x-ray imaging
      systems based on CCD camera is discussed, and the structure and principle of an
      auto brightness control loop are analyzed along with the working procedure of the
      x-ray imaging system. A kind of digital brightness controller about a typical
      device and the designing idea of the computer brightness intelligent control
      software is introduced.

PMID- 16104316
TI  - [A new compositive algorithm of ST-segment].
AB  - In this paper we introduce a new algorithm about ST-segment--Triangle way. At the
      same time, based on analyzing all kinds of algorithms, we have summarized a
      compositive algorithm used to detect the emulating data. The testing result shows
      that the algorithm, which is easy to use, has a high speed and a good accuracy.

PMID- 16104317
TI  - [Development of RF ablation therapeutic instrument based on improved PID
      algorithm].
AB  - The development of a RF ablation therapeutic instrument based on improved PID
      algorithm is introduced here. It is based on the theory of radio frequency local
      destruction. By adopting the improved PID temperature control algorithm, the
      problem of the temperature control precision reduction due to tumor tissue
      characteristic changing by heating has been solved, thus ensuring homogeneous and
      smooth radio frequency heating to tumor foci. Experiments demonstrate that the
      new algorithm has strong adaptability and anti-disturbance capability, the
      equipment works stably and reliably, and can control therapeutic temperature
      precisely (+/- 2 degrees C), which indicates a good clinical application value.

PMID- 16104318
TI  - [The research on accuracy of computer-assisted surgery].
AB  - The computer-assisted surgery system is a complex system. All of the errors can
      be attributed to the loss of correspondence between the world coordinate system
      in the operation room and the virtual world coordinate system obtained from the
      multi-model medical images. The system's accuracy is composed of the accuracy of
      the localizer and that of registration. In order to improve the system accuracy,
      we analyse most of the possible error sources. The accuracy of the localizer
      affects deeply the registration between the intra-operation and pre-operation
      data. The localizer is the most basic and important part for a computer-assisted
      surgery system. We give a comprehensive possible error source at the end of the
      paper.

PMID- 16104319
TI  - [A slip-coordinate system that applied in the extra-cranial stereotactic
      radiosurgery treatment system].
AB  - In this paper, we introduce a slip-coordinate system that applied in the extra
      cranial stereotactic radiosurgery treatment system (by the name of extra-cranial
      X-Knife), and make an analysis about the correlative formula.

PMID- 16104320
TI  - [Some technical problems in setting up hospital PACS].
AB  - Having introduced PACS in brief, this paper presents some technical problems such
      as the selection of scale, function, database and monitor. And many solutions for
      these problems are given and compared with each other.

PMID- 16104321
TI  - [The circuit design of an alarm system for the old solitary man based on daily
      life].
AB  - The system with DS1302 as its clock makes one hour as one basic time unit, and
      thus there will be 24 monitoring segments in a day. It watches the movements of
      the aged through the sensors placed in the house-rooms such as bedroom, kitchen,
      and obtains the data of the movements and activities. Based on the data the MCU
      (Micro Control Unit) will make an hourly judgment whether the movements and
      activities are normal ones. When the system makes sure they are abnormal, it will
      dial out the setting telephone saved in EEPROM, waiting for the other end to pick
      up phone and then will send the tone alarm out. Once an accident happens, the
      alarm will be started up immediately by pressing the emergency button of the
      remote control. When the aged is out, he or she can shift the health mode to the
      away mode by the remote control, and the system will act as a home security
      system. In simulation experiments, the system works well at recognizing the data
      of movements and has a very low mis-alarm ratio. The system provides a viable
      solution to the social problem of looking after the aged who lives alone.

PMID- 16104322
TI  - [The design and implementation of real-time MPEG-2 video transmission in
      telemedicine system].
AB  - It is particularly important for telediagnosis to transmit diagnostic video in
      real time. Firstly, we introduce image compression, multithread and multicast
      technology, then a solution is provided for the real-time video transmission
      system based on TCP/IP LAN.

PMID- 16104323
TI  - [Development of the coaxial-cylinders-type coagulometer].
AB  - Through the detection of the change of shear stress in blood, four coagulation
      parameters (t(r), delta tau/delta t, tau(max), S) can be automatically
      determined. The instrument can be used to automatically detect the process of
      blood coagulation and print coagulation curves. There is a great difference
      between different samples while there is a good repeatability with the same
      sample.

PMID- 16104324
TI  - [A computer processing system for bronchoscopes images].
AB  - A new equipment of a computer multimedia system combined with a bronchoscope is
      presented here, which is able to provide active images with a high definition,
      image capture, synchronized video recording and playback during bronchoscopy. Its
      operation is easy and its quality is reliable. It is an advanced product for
      endoscopies and is worth while to be applied to clinical application.

PMID- 16104325
TI  - [Non-invasive temperature estimation using backscattered ultrasound].
AB  - This article describes non-invasive temperature estimation using backscattered
      ultrasound based on the random medium model of biotissue. Its model, algorithm
      and key technology are introduced here and its development trend is discussed
      too.

PMID- 16104326
TI  - [The development and applications of electrosurgical equipment].
AB  - We here in the paper, not only introduce the development of electricsurgical
      operation equipment in our country and foreign countries but also represent the
      characters, principles and usages of several kinds electrosurgical equipment in
      foreign countries.

PMID- 16104327
TI  - [The development and application in clinical programme of SPECT].
AB  - On the base of original computer software of Elscint Apex 609 RG SPECT, two
      clinical application programmes are successfully designed for clinical engineers
      to explore and practise by using the CLIP (The Clinical Interpreter Programming)
      language.

PMID- 16104328
TI  - [WEIDA LMW-1000 magnetic resonance imaging system communication with Windows 98
      computer].
AB  - This paper introuduces two ways of WEIDA LMW-1000 Magnetic Resonance Imaging
      System's communication with Windows 98 computer. It has a practical value to the
      improvement of the system's operation interface.

PMID- 16104329
TI  - [The development and clinical application of the penetrater for stomach wall].
AB  - This paper introduces the design principles of a penetrator for stomach wall, and
      its operating method. All the experimental results show that it is a very
      practical, safe and is a useful medical device while used with the GF-I Model
      Anastomat in esophagogastro-anastomosis. It may prevent the anastotic stoma
      complication and may be of great importance in clinical applications.

PMID- 16104330
TI  - [The application and programming of digital potentiometers in medical
      instruments].
AB  - Digital potentiometers have been used in medical instruments. This paper
      describes the structure and principle of a digital potentiometer, especially its
      interfacing with a single chip processor and its programming.

PMID- 16104331
TI  - [The adjustable, folding and multi-function mount].
AB  - An adjustable folding mount is presented in this paper. It is a multi-functional
      device for one or more patient's infusions, continuous traction and functional
      training, and life nursing etc.

PMID- 16104332
TI  - Lawrence Friedman: speaking of analysis.

PMID- 16104333
TI  - Flirting with virtual reality.
AB  - Psychoanalysis encourages patients to experience a virtual reality of the
      psychoanalytic relationship, in which both image and wish can be experimented
      with. Originally, the patient's awareness was supposed to move back and forth
      between the virtual and the actual, in a flickering and uncertain fashion. That
      is uncomfortable, and analysts have often preferred the domain of virtuality or
      of actuality, or have denied the distinction altogether. Recent philosophical
      developments and doubts about transference neurosis and reconstruction further
      tempt analysts to relax the flickering uncertainty of virtual and actual. Patient
      and analyst may gain comfort but lose something in the process.

PMID- 16104334
TI  - Nested ideation and the problem of reality: dreams and works of art in dreams.
AB  - This study uses seven well-analyzed dreams to establish three empirical
      generalizations about dreams and works of art nested in dreams: (1) Those dreams
      attempt to deny a painful reality in some way depicted in the nested element; (2)
      they present an antithetical view of that reality (both denying and affirming);
      and (3) they are consistently associated with the problem of reality (the problem
      of deciding what is real or true). The explanation of these empirical
      generalizations is based on a hypothesis derived from Freud's 1911 formulation of
      the dream within a dream.

PMID- 16104335
TI  - Knowing and not knowing: the analyst's pregnancy.
AB  - The author examines some of the dynamics associated with the shifting experience
      of knowing and not knowing as it arises in response to the pregnancy of the
      analyst. This experience, as well as the thinking process behind it, is
      ubiquitous in psychoanalytic work, but is particularly apparent in the work
      demanded by the analyst's pregnancy. An indepth case history is presented to
      illustrate the ways in which pregnancy in the analyst may powerfully revive
      important dimensions of the patient's past.

PMID- 16104336
TI  - The therapeutic effects of the free-associative state of consciousness.
AB  - Free association is therapeutically helpful in the regulation of states of
      consciousness. A person who free-associates enters a particular state of
      consciousness characterized by increased subjective self-awareness and disregard
      for reality, together with implicit pulls for objective self-awareness and
      reality adherence. Free association facilitates the patient's learning to
      integrate and to shift flexibly among points on these dimensions. Tensions
      existing in the free-associative state are embedded in a similar tension between
      free associating and reacting to the analyst's interventions, so interplay
      between free association and intervention also facilitates regulation of states
      of consciousness.

PMID- 16104337
TI  - The fundamental importance of simple operational definitions of introspection and
      empathy.
AB  - Instead of asking why psychoanalysis has lost its central position in mental
      health, one might marvel at its longevity when considering that psychoanalysts
      have not attained agreement about basic methods for observing unconscious
      mentation, either their own or that of others. Ambiguity abounds regarding the
      operations involved in, and the usefulness of, introspection, and even more so of
      empathy. Simple operational definitions of introspection and empathy are proposed
      in this article, definitions that are sufficiently abstract to transcend
      particular theories of mental organization (e.g., ego psychology, object
      relations, and self psychology) and concrete enough to be practicable.

PMID- 16104338
TI  - Loewald's approach to psychoanalytic theory.
AB  - The author suggests that part of the legacy of Hans Loewald is the nature of his
      approach to psychoanalytic theory. Loewald carefully considered and selectively
      utilized the work of theorists from a number of psychoanalytic schools of
      thought: id psychology, object relations theory, ego psychology, self psychology,
      and the interpersonal tradition. In addition, he helped pave the way for the
      current widespread interest in intersubjectivity, and also positioned himself in
      relation to those who embraced hermeneutics. Through all of this, he maintained a
      skeptical attitude, embodied in his belief in the complexity of the phenomena to
      be explored and his commitment to the perspective that psychoanalytic ideas
      should be open to revision.

PMID- 16104339
TI  - Generating words: one approach to teaching clinical writing.
AB  - Language is our means of reaching our patients and our means of describing the
      process of analysis to others. The task of the case history is to show the
      evolution of consciousness in both analyst and patient. It will be more effective
      if written in a lively engaging way. The author describes one method of teaching
      clinical writing, introducing candidates to techniques of fiction writing and
      poetry. Her class has involved both focused reading and writing exercises;
      examples are given of both.

PMID- 16104340
TI  - Tracking the case-mix adjustment: were the fiscal intermediaries ready?

PMID- 16104341
TI  - U.S. diabetics struggling to control blood glucose.

PMID- 16104342
TI  - A single center experience in the use of polyurethaneurea arteriovenous grafts.
AB  - BACKGROUND: Polytetrafluoroethylene (PTFE) grafts often require temporary
      catheters, which increase costs as well as risk of infection, bleeding, and poor
      blood flow. Polyurethaneurea (PUU) grafts can be cannulated within 24 hours of
      placement, avoiding the need for temporary catheters. METHODS: Hemodialysis
      patients who were not candidates for arteriovenous fistula (AVF) were eligible
      for the study. Those requiring urgent (<48 hours) hemodialysis access received
      PUU grafts; all others received PTFE grafts. One surgeon performed all
      implantations. RESULTS: 133 PUU grafts were implanted, 31 (24%) patients died
      (unrelated to graft placement). Within the first 4 days after graft placement,
      108 of 133 grafts (81%) were cannulated. None required a temporary catheter. Of
      102 surviving patients, 50 (49%) had graft thrombosis; 47/50 (94%) underwent
      successful percutaneous thrombectomy (PT). Primary patency at 6 months and at 1
      year was 51% and 33%, respectively. Secondary patency at 6 months and 1 year was
      78% and 61%, respectively. Mean bleeding time (after withdrawal of dialysis
      needle) was 4.0 (range 1-14) minutes in PUU grafts vs. 9.2 (1-30) minutes in PTFE
      grafts. CONCLUSIONS: Polyurethane graft placement allowed early graft cannulation
      without temporary catheters. Patency rates are comparable with previous reports.
      Decreased bleeding time with PUU grafts reduced aggregate blood exposure for
      patients and staff, lowering the risk of infection and anemia exacerbation and
      speeding time between treatments.

PMID- 16104343
TI  - Merger mania: and then there were two.

PMID- 16104344
TI  - Bracing for impact: the renal community awaits the effects of the latest mergers.

PMID- 16104345
TI  - Medicare and rural kidney medicine.

PMID- 16104346
TI  - Dialysis facility joint ventures--current structures and issues.
AB  - With the ongoing consolidation of the health care industry, including renal care,
      providers and physicians alike are using joint ventures as a means to partner on
      business transactions. This article discusses the expanding use of joint ventures
      in health care, including the dialysis industry, and looks at the types of
      structures being utilized and key legal concerns relating to such structures and
      issues.

PMID- 16104347
TI  - Pay-for-performance: show me the (value of) money.

PMID- 16104348
TI  - Microcella putealis gen. nov., sp. nov., a gram-positive alkaliphilic bacterium
      isolated from a nonsaline alkaline groundwater.
AB  - Three Gram-positive bacteria designated CV-2T, CV-40 and AC-30 were isolated from
      a highly alkaline groundwater environment (pH 11.4). These organisms formed very
      small rod-shaped cells, are aerobic, non-spore-forming, catalase-positive,
      oxidase-negative, with an optimum growth temperature of 35 degrees C and optimum
      pH value of growth between 8.5 and 9.0. The strains possessed a novel B-type cell
      wall peptidoglycan structure with lysine as the diamino acid; the major
      respiratory quinones were menaquinone 12 (MK12) and MK13. The G + C content of
      DNA was between 67.1 and 70.7 mol%. The phylogenetic analyses of the sequences of
      the 16S rRNA genes reveled that they formed a deep branch within the family
      Microbacteriaceae, with the highest similarity of approximately 95.6% with
      members of the genera Agreia, Agrococcus, Cryobacterium, Clavibacter,
      Frigoribacterium, Leifsonia, Mycetocola, Rhodoglobus, Salinibacterium and
      Subtercola. Based on the phylogenetic analyses and distinct phenotypic
      characteristics, we are of the opinion that strains CV-2T, CV-40 and AC-30,
      represent a new species of a novel genus within the family Microbacteriaceae for
      which we propose the name Microcella putealis gen. nov., sp. nov.

PMID- 16104349
TI  - Streptomyces pharetrae sp. nov., isolated from soil from the semi-arid Karoo
      region.
AB  - An actinomycete, strain CZA14T, was isolated from Worcester in the Western Cape
      province of South Africa. Based on rapid genus identification, 16S-rDNA sequence
      similarities and chemotaxonomy, strain CZA14T was identified as a member of the
      genus Streptomyces. It exhibited weak antibiosis against Bacillus coagulans ATCC
      7050T, Mycobacterium aurum A+ and Acinetobacter calcoaceticus C91. The results of
      physiological tests and analysis of the 16S-rDNA sequence allowed for the
      differentiation of strain CZA14T from other species of the genus Streptomyces.
      Strain CZA14T therefore represents a new species for which the name Streptomyces
      pharetrae is proposed, with the type strain CZA14T (= DSM 41856T = NRRL 24333T).

PMID- 16104350
TI  - Reclassification of Xanthomonas campestris pv. citri (ex Hasse 1915) Dye 1978
      forms A, B/C/D, and E as X. smithii subsp. citri (ex Hasse) sp. nov. nom. rev.
      comb. nov., X. fuscans subsp. aurantifolii (ex Gabriel 1989) sp. nov. nom. rev.
      comb. nov., and X. alfalfae subsp. citrumelo (ex Riker and Jones) Gabriel et al.,
      1989 sp. nov. nom. rev. comb. nov.; X. campestris pv malvacearum (ex smith 1901)
      Dye 1978 as X. smithii subsp. smithii nov. comb. nov. nom. nov.; X. campestris
      pv. alfalfae (ex Riker and Jones, 1935) dye 1978 as X. alfalfae subsp. alfalfae
      (ex Riker et al., 1935) sp. nov. nom. rev.; and "var. fuscans" of X. campestris
      pv. phaseoli (ex Smith, 1987) Dye 1978 as X. fuscans subsp. fuscans sp. nov.
AB  - Bacterial canker of citrus is a serious disease of citrus worldwide. Five forms
      of the disease have been described, cankers "A", "B", "C", "D", and "E". Although
      considerable genetic diversity has been described among the causal agents of the
      five forms of citrus canker and supports multiple taxons, the causal agents
      currently are classified as pathovars citri ("A"), aurantifolii ("B/C/D") and
      citrumelo ("E") of a single species, Xanthomonas campestris pv. citri (or X.
      axonopodis pv. citri). To determine the taxonomic relatedness among strains of X.
      campestris pv. citri, we conducted DNA-DNA relatedness assays, sequenced the 16S
      23S intergenic spacer (ITS) regions, and performed amplified fragment length
      polymorphism (AFLP) analysis, using 44 strains representative of the five
      recognized forms of citrus canker. Under stringent DNA reassociation conditions
      (Tm - 15 degrees C), three distinct genotypes of citrus pathogens were revealed:
      taxon I included all "A" strains; taxon II contained all "B", "C", and "D"
      strains; and taxon III contained all "E" strains. The three citrus taxa showed
      less than 50% (mean) DNA-DNA relatedness to each other and less than 30% (mean)
      to X. campestris pv. campestris and X. axonopodis pv. axonopodis. Taxa I and II
      strains share over 70% DNA relatedness to X. campestris pv. malvacearum and X.
      campestris pv. phaseoli var. fuscans, respectively (at Tm - 15 degrees C). Taxon
      III strains share 70% relatedness to X. campestris pv. alfalfae. Previous and
      present phenotypic data support these DNA reassociation data. Taxon II strains
      grow more slowly on agar media than taxa I and III strains. Taxa I and III
      strains utilize maltose, and liquefy gelatin whereas taxon II strains do not.
      Taxon I strains hydrolyze pectate (pH 7.0) whereas Taxon II strains do not. Taxon
      III strains utilize raffinose whereas Taxon I strains do not. Each taxon can be
      differentiated by serology and pathogenicity. We propose taxa I, II, and III
      citrus strains be named, respectively, Xanthomonas smithii subsp. citri (ex
      Hasse, 1915) sp. nov. nom. rev. comb. nov., Xanthomonas fuscans subsp.
      aurantifolii (ex Gabriel et al., 1989) sp. nov. nom. rev. comb. nov., and
      Xanthomonas alfalfae subsp. citrumelo (ex Riker and Jones) Gabriel et al., 1989
      nov. rev. comb. nov. Furthermore, based on the analysis of 40 strains of 19 other
      xanthomonads, we propose to reclassify X. campestris pv. malvacearum (ex Smith,
      1901) Dye 1978 as X. smithii subsp. smithii sp. nov. comb. nov. nom. nov.; X.
      campestris pv. alfalfae (ex Riker and Jones) Dye 1978 as X. alfalfae subsp.
      alfalfae (ex Riker et al., 1935) sp. nov. nov. rev.; and "var. fuscans" (ex
      Burkholder 1930) of X. campestris pv. phaseoli (ex Smith, 1897) as X. fuscans
      subsp. fuscans sp. nov.

PMID- 16104351
TI  - Diversity and technological properties of predominant lactic acid bacteria from
      fermented cassava used for the preparation of Gari, a traditional African food.
AB  - Traditional fermentation of cassava is dominated by a lactic acid bacteria (LAB)
      population. Fermentation is important for improving product flavour and aroma as
      well as safety, especially by reduction of its toxic cyanogenic glucosides. The
      production of Gari from cassava in Benin typically occurs on a household or small
      industrial scale, and consequently suffers from inconsistent product quality and
      may not always be safe for consumption. Therefore, the diversity of LAB from a
      typical cassava fermentation for the preparation of Gari, and their
      technologically relevant characteristics were investigated with a view towards
      selection of appropriate starter cultures. A total of 139 predominant strains
      isolated from fermenting cassava were identified using phenotypic tests and
      genotypic methods such as rep-PCR and RAPD-PCR. DNA-DNA hybridisation and
      sequencing of the 16S rRNA genes were done for selected strains. Lactobacillus
      plantarum was the most abundantly isolated species (54.6% of isolates), followed
      by Leuconostoc fallax (22.3%) and Lactobacillus fermentum (18.0%). Lactobacillus
      brevis, Leuconostoc pseudomesenteroides and Weissella paramesenteroides were
      sporadically isolated. The L. plantarum strains were shown to be better acid
      producers and capable of faster acid production than the L. fallax or L.
      fermentum strains. The incidence of beta-glucosidase (linamarase) activity was
      also highest among strains of this species. Production of antagonistic substances
      such as H2O2 and bacteriocins, however, was more common among L. fallax and L.
      fermentum strains. Strains of all three species were capable of utilising the
      indigestible sugars raffinose and stachyose. Therefore, a starter culture
      containing a mixture of strains from all three species was recommended.

PMID- 16104352
TI  - Molecular detection and isolation from antarctica of methylotrophic bacteria able
      to grow with methylated sulfur compounds.
AB  - This study is the first demonstration that a diverse facultatively methylotrophic
      microbiota exists in some Antarctic locations. PCR amplification of genes
      diagnostic for methylotrophs was carried out with bacterial DNA isolated from 14
      soil and sediment samples from ten locations on Signy Island, South Orkney
      Islands, Antarctica. Genes encoding the mxaF of methanol dehydrogenase, the fdxA
      for Afipia ferredoxin, the msmA of methanesulfonate monooxygenase, and the 16S
      rRNA gene of Methylobacterium were detected in all samples tested. The mxaF gene
      sequences corresponded to those of Hyphomicrobium, Methylobacterium, and
      Methylomonas. Over 30 pure cultures of methylotrophs were isolated on
      methanesulfonate, dimethylsulfone, or dimethylsulfide from ten Signy Island
      lakes. Some were identified from 16S rRNA gene sequences (and morphology) as
      Hyphomicrobium species, strains of Afipia felis, and a methylotrophic
      Flavobacterium strain. Antarctic environments thus contain diverse methylotrophic
      bacteria, growing on various C1-substrates, including C1-sulfur compounds.

PMID- 16104353
TI  - Occurrence and molecular characterization of cultivable mesophilic and
      thermophilic obligate anaerobic bacteria isolated from paper mills.
AB  - The aim of this work was to characterize the cultivable obligate anaerobic
      bacterial population in paper mill environments. A total of 177 anaerobically
      grown bacterial isolates were screened for aerotolerance, from which 67 obligate
      anaerobes were characterized by automated ribotyping and 41 were further
      identified by partial 16S rDNA sequencing. The mesophilic isolates indicated 11
      different taxa (species) within the genus Clostridium and the thermophilic
      isolates four taxa within the genus Thermoanaerobacterium and one within
      Thermoanaerobacter (both formerly Clostridium). The most widespread mesophilic
      bacterium was closely related to C. magnum and occurred in three of four mills.
      One mill was contaminated with a novel mesophilic bacterium most closely related
      to C. thiosulfatireducens. The most common thermophile was T.
      thermosaccharolyticum, occurring in all four mills. The genetic relationships of
      the mill isolates to described species indicated that most of them are potential
      members of new species. On the basis of identical ribotypes clay could be
      identified to be the contamination source of thermophilic bacteria. Automated
      ribotyping can be a useful tool for the identification of clostridia as soon as
      comprehensive identification libraries are available.

PMID- 16104354
TI  - PCR detection assays for the trichothecene-producing species Fusarium
      graminearum, Fusarium culmorum, Fusarium poae, Fusarium equiseti and Fusarium
      sporotrichioides.
AB  - Contamination of small-grain cereals with the fungal species Fusarium
      graminearum, F. culmorum, F. poae, F. sporotrichioides and F. equiseti is an
      important source of trichothecenes, Zearalenone and other mycotoxins which cause
      serious diseases in human and animals. Additionally, these species contribute to
      Fusarium Head Blight, a disease which produces important losses in cereal yield.
      Early detection and control of these Fusarium species is crucial to prevent
      toxins entering the food chain and a useful tool in disease management practices.
      We describe the development of specific PCR assays to F. graminearum, F.
      culmorum, F. poae, F. sporotrichioides and F. equiseti using DNA from pure fungal
      cultures as well as from naturally infected wheat seeds, using in this case a
      rapid and easy protocol for DNA isolation. The specific primers were designed on
      the basis of IGS sequences (Intergenic Spacer of rDNA), a multicopy region in the
      genome that permits to enhance the sensitivity of the assay in comparison with
      PCR assays based on single-copy sequences.

PMID- 16104355
TI  - Pathology of thymic tumors.
AB  - As the thymus is composed of heterogeneous admixture of lymphoid and epithelial
      elements, tumors originating in the thymus may be of varied histologic types.
      Thymomas are the most common thymic tumor in adults. Thymoma classification has
      historically been controversial, but a system put forth by the World Health
      Organization (WHO) in 2004 has been generally accepted as a reproducible and
      clinically relevant classification. In addition to histologic subtype, tumor
      stage and resection status are important factors in determining outcome in
      thymomas. Thymic lymphomas typically occur in younger patients than thymomas. The
      most common thymic lymphomas are precursor T-lymphoblastic lymphoma, Hodgkin
      lymphoma, and primary mediastinal large B-cell lymphoma. Thorough histologic
      sampling and, in some cases, the appropriate use of ancillary studies such as
      immunohistochemistry, flow cytometry, and molecular studies, are important in
      proper pathologic evaluation of thymic tumors.

PMID- 16104356
TI  - Imaging of thymoma.
AB  - Thymomas are the most common mediastinal tumors, usually diagnosed initially by
      CT. CT scanning can aid in characterization of thymoma and can successfully
      distinguish thymomas from other benign mediastinal tumors and from lymphoma.
      However, many of the primary mediastinal masses demonstrate overlap between
      imaging features and frequently resection is advisable for definitive
      characterization.

PMID- 16104357
TI  - Surgical treatment of thymic tumors.
AB  - Thymoma is a rare neoplasm usually with an indolent growth pattern; however,
      local invasion and/or metastases may occur. The association with several
      paraneoplastic syndromes, especially myasthenia gravis, makes thymoma an
      interesting biologic tumor model. Surgery has been the standard of care for early
      stage disease with high cure rates anticipated. Multimodality therapy can result
      in long-term disease-free survival for patients presenting with locally advanced
      disease.

PMID- 16104358
TI  - Treatment of recurrent thymic tumors.
AB  - Surgery is the cornerstone of therapy for recurrent thymic tumors. The pattern of
      recurrence is, however, less defined. Between 1966 and 1988, we operated on 83
      patients with thymoma, 11 of whom underwent surgery for recurrence (group I). In
      1989, we initiated a prospective multimodality protocol and have enrolled 128
      patients with 9 (7%) recurrences since (group II). In group I, 1 patient was
      originally at stage I, 2 were at stage II, 5 at stage III, and 3 at stage IV. The
      patients underwent 1 (#10) or 2 (#1) reoperations and 5 showed histological
      progression of malignancy. One patient died postoperatively, 6 died of disease,
      and 3 are alive and disease free 18 to 22 years after the first operation. In
      group 2, no patient was originally at stage I, 1 was at stage II, 4 were at stage
      III, and 4 at stage IV. Reoperation (5 patients) was followed by chemotherapy and
      2 showed histological progression of disease. One patient died after 2 years, and
      4 patients are alive after 6 to 11 years. All recurrent tumors were thymomas with
      cortical differentiation. Early onset of recurrence was a negative prognostic
      factor. Thymomas can recur also at early stages. A multimodality approach is
      indicated also for early stage lesions based on histology.

PMID- 16104359
TI  - Radiation therapy in the management of thymic tumors.
AB  - Thymic tumors including thymomas, thymic carcinomas, and thymic carcinoid tumors,
      are relatively infrequent. These tumors with a wide spectrum of histological and
      biological features may exhibit an indolent clinical course (thymomas) or
      manifest an aggressive behavior (thymic carcinoma) with a high risk of relapse
      and metastasis. Successful management of these tumors depends on accurate
      diagnosis, thorough staging, proper assessment of patient health status, and
      selection of treatment modality. Surgery remains the mainstay of therapy whereas
      radiation therapy plays an important role in subtotally resected or unresectable
      cases. The risk of side effects and late sequelae is generally low when proper
      radiation technique is employed. This review examines the current role of
      radiation therapy in the management of these tumors.

PMID- 16104360
TI  - Role of chemotherapy in the management of advanced thymic tumors.
AB  - Chemotherapy has an important role in the treatment of advanced thymic tumors.
      Early stage tumors are successfully treated with surgery. Locally advanced tumors
      (Masaoka stage III and IVA) are often treated with combined modality treatment
      including surgery, radiation, and chemotherapy. For patients with curable thymic
      tumors, the ability to attain a complete resection is a critical prognostic
      factor. Locally advanced tumors have a relatively high risk of recurrence and
      decreased rates of long-term survival. A multimodality approach including
      induction chemotherapy and postoperative radiation therapy can improve complete
      resection rates and long-term outcomes. Thymic tumors are chemoresponsive with
      optimal responses achieved with cisplatin-based combination chemotherapy.
      Chemotherapy with radiation can result in long-term progression-free survival for
      patients with locally advanced disease who remain inoperable following induction
      therapy. Patients with disseminated (stage IVB) thymic tumors can also have
      significant disease response and palliation of symptoms when treated with
      chemotherapy. Octreotide and corticosteroids also have shown efficacy. For best
      results, it is important that thoracic surgeons, radiation oncologists, and
      medical oncologists work together to obtain the best local control of tumor and
      optimal treatment of metastases.

PMID- 16104361
TI  - Antifibrinolytic agents in cardiac surgery: current controversies.
AB  - Antifibrinolytic agents play a prominent role in adult cardiac surgery. This
      article is a review of the modern published experience of antifibrinolytic agent
      use in adult cardiac surgery. The use of tranexamic acid, epsilon-aminocaproic
      acid, and aprotinin is examined during primary cardiac surgery, deep hypothermic
      circulatory arrest, reoperative cardiac surgery, and off-pump coronary artery
      bypass surgery. In addition, the issues of vein graft patency and
      hypersensitivity reaction in the presence of antifibrinolytic agents are
      examined.

PMID- 16104362
TI  - Antithrombotic controversies in off-pump coronary bypass.
AB  - The purpose of this article is to evaluate the use of perioperative
      antithrombotics in patients undergoing surgical revascularization of the coronary
      vessels. Although there is a general agreement about the use of anticoagulation
      during off-pump coronary revascularization (OPCAB), the degree of the required
      anticoagulation varies from one center to another. The review is divided into
      four major sections. The first section describes the pathophysiology of the
      coagulation system in cardiac surgery with and without the use of cardiopulmonary
      bypass. In this section, we also discuss the interactions between the coagulation
      system and the inflammatory response to cardiac surgery. The second section
      examines the role of prophylactic antithrombosis in patients referred to surgical
      revascularization, and their role in bleeding complications associated with
      surgery. Heparinization and neutralizing its anticoagulative effects during
      coronary surgery are discussed in the third section. The fourth section examines
      the evidence that the inflammatory response contributes to adverse peri-operative
      events, in particular organ dysfunction, and potential therapeutic strategies to
      control this response. The review concludes with a summary of potential future
      research directions and key deficiencies in our knowledge regarding the use of
      anticoagulants in cardiac surgery.

PMID- 16104363
TI  - Cardiac surgery in patients on antiplatelet and antithrombotic agents.
AB  - The widespread application of antithrombotic agents carries significant potential
      for inducing excessive peri-operative hemorrhage during cardiac surgery. Specific
      surgical and medical strategies can be employed to attenuate this bleeding. These
      antithrombotic agents and anti-hemorrhagic measures will be reviewed in depth.

PMID- 16104364
TI  - Mechanistic basis of heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) occurs in 1% to 5% of patients treated
      with unfractionated high-molecular weight heparin and often results in limb-
      and/or life-threatening thrombotic complications. This disorder involves the
      formation of antibodies to a complex of Platelet Factor 4 (PF4) with the heparin.
      We believe that the pathogenesis of this disease begins with having an excess of
      platelet PF4 release. The freed PF4 is bound to platelet and other vascular
      membrane surfaces and has three critical roles in the initiation of HIT. (1)
      Infused heparin neutralizes a portion of excess surface PF4, directly enhancing
      local thrombosis. (2) The excess PF4 is mobilized into PF4/heparin complexes that
      stimulates HIT antibody production. (3) The remaining PF4 complexed to
      heparanoids and heparin on the vascular surfaces now bind to these HIT antibodies
      and through surface Fc gammaRII receptors leads to more platelet activation and
      removal, thrombus formation, and inflammation. These events, in turn, further
      stimulate PF4 release, perpetuating repetitive cycle that results in the clinical
      manifestations of this disorder.

PMID- 16104365
TI  - Clinical presentation and laboratory diagnosis of heparin-induced
      thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) type II is an immune mediated reaction in
      which pathologic antibodies develop to a complex composed of heparin and the
      platelet-derived alpha granule protein, platelet factor 4 (PF4). HIT must be
      recognized quickly so as to eliminate all heparin exposure from a patient's
      clinical care. Thrombosis (HIT) may accompany thrombocytopenia resulting in limb
      and life-threatening complications. Despite a higher incidence of subclinically
      detectable heparin-PF4 antibody formation in the cardiac care setting, the
      development of the full clinicopathologic syndrome occurs in approximately 2% to
      3% of patients, similar to the incidence in other clinical scenarios.

PMID- 16104366
TI  - Anticoagulation management and cardiac surgery in patients with heparin-induced
      thrombocytopenia.
AB  - Unfractionated heparin (UFH) is the gold standard for anticoagulation during
      cardiopulmonary bypass (CPB). Of patients undergoing CPB operations, 25% to 50%
      develop heparin-dependent antibodies during the postoperative period, typically
      between day 5 and 10, if UFH is continued during the postoperative course. In 1%
      to 3% of all patients undergoing CPB operation with UFH anticoagulation, these
      antibodies activate platelets causing a prothrombotic disorder, known as heparin
      induced thrombocytopenia (HIT), which can lead to life-threatening thromboembolic
      complications. If urgent cardiac operation with the use of CPB in patients with
      positive antibody titer is required, different anticoagulatory approaches are
      available, such as lepirudin, bivalirudin, and danaparoid or UFH in combination
      with platelet antagonists, such as epoprostenol or tirofiban. In patients with
      previous HIT but no detectable antibodies, UFH alone can be used only during CPB,
      but alternative anticoagulation has to be used pre- and postoperatively.

PMID- 16104367
TI  - Vital statistics and select life tables: any relationships?

PMID- 16104368
TI  - An iterative method of estimating excess death rates and mortality ratios.
AB  - OBJECTIVES: To present a method of comparative mortality analysis of published
      data that can be applied when age- and sex-specific mortality rates for the study
      population are not available. METHODS: The quantitative method is described and
      illustrated using data from the SHEP study. A comparison is made with the results
      of Singer.

PMID- 16104369
TI  - An analytic method for longitudinal mortality studies.
AB  - Our knowledge of mortality risks comes largely from longitudinal (cohort)
      studies. The most commonly used analytic tool is the Cox proportional hazards
      model for survival analysis. An alternative approach is a simple cross-sectional
      analysis of person-years. The key to the method is logistic regression, where the
      outcome variable is lived/died in the given year and the explanatory variables
      are age, sex, and other potential risk factors. This approach can be used to
      model any dichotomous outcome and has several important advantages over the more
      traditional survival analysis. As an example, we compare the two methods using a
      large data base of patients with spinal cord injury.

PMID- 16104370
TI  - Long-term insured lives morbidity and mortality risk associated with chronic
      hepatitis C virus infection.
AB  - BACKGROUND: Hepatitis C virus (HCV) infects 170 million people worldwide. Some
      medical experts have suggested that progression to end-stage liver disease is
      inevitable; others have concluded that progression is restricted to a limited
      percentage of those who are infected. These opposing views have added to the
      uncertainty faced by underwriters who must assess risk in applicants infected
      with HCV. This article discusses use of a Markov model to estimate risk
      associated with chronic HCV infection in otherwise healthy applicants for life
      and critical illness insurance. RESULTS: Estimated mortality ratios varied with
      assumptions regarding rate of progression from active HCV infection to cirrhosis.
      For males, peak mortality ratios decreased with advancing age at underwriting
      from a high of 209% (age 20) to a low of 122% (age 60). A similar age-related
      pattern was seen for females, from a peak mortality ratio of 184% (age 20) to a
      low of 128% (age 60). In contrast to the pattern of decreasing relative mortality
      at older ages, morbidity increased with age at underwriting. Sensitivity analysis
      indicated that calculations in the model were sensitive to different transition
      rates from active HCV infection to cirrhosis and from cirrhosis to hepatocellular
      carcinoma (HCC) but not sensitive to treatment frequency and success. A review of
      the literature also suggested that a favorable prognosis was likely in applicants
      with persistently normal alanine aminotransferase (ALT) levels, but prognosis was
      less certain for those with intermittent or persistent elevation of liver
      enzymes. CONCLUSION: Morbidity and mortality are within the insurable range for
      the majority of HCV-infected persons. Risk varies with gender, age at infection,
      and other variables discussed in the article.

PMID- 16104371
TI  - Long-term survival of patients with Wegener's granulomatosis.

PMID- 16104373
TI  - Frequent premature ventricular contractions.
AB  - Premature ventricular contractions (PVCs) are considered normal in many
      circumstances but can act as markers to other cardiac disease such as
      cardiomyopathy and ischemic heart disease. This case is presented to illustrate
      frequent PVCs as a marker for serious heart disease.

PMID- 16104372
TI  - Mortality in two recent reports of clinical trials on patients with congestive
      heart failure compared with mortality in three previous clinical trials.
AB  - BACKGROUND: Several clinical trials of drug treatment of patients with congestive
      heart failure (CHF) have previously been reported as Mortality Abstracts in the
      Journal of Insurance Medicine. Results are presented here for two similar
      clinical trials reported in September 1999 and compared with the previous
      results. RESULTS: In a recent international multicenter clinical trial, excess
      mortality in terms of excess death rates (EDRs) was reduced from 195 per 1000 per
      year in the placebo group to 139 in the group treated with Spironolactone. There
      was no significant reduction in the Danish multicenter study of Dofetilide to
      convert the atrial fibrillation (AF) to a normal rhythm in the 25% of the CHF
      patients who had AF (EDR was 224 in the placebo group and 216 in the Dofetilide
      group). In both of these studies, there were more patients with severe CHF than
      in the previous studies and the EDR values were higher. Results from the Danish
      study by severity according to the New York Heart Association (NYHA)
      classification show a progressive increase in EDR from 173 in class 2 to 237 in
      class 3 to 392 in class 4. CONCLUSION: Excess mortality in symptomatic CHF is far
      outside the issue limits for individual life insurance, but these results are of
      potential utility for the underwriting of such cases for structured settlement
      annuities.

PMID- 16104374
TI  - A gun-cleaning "accident".
AB  - A case is presented in which the question of suicide is raised. Several pointers
      are outlined to help in this differentiation.

PMID- 16104375
TI  - Diabetes mellitus: new guidelines.
AB  - The American Diabetes Association adopted new guidelines for the diagnosis of
      diabetes mellitus in 1997.

PMID- 16104376
TI  - A short history of mortality.
AB  - A short history of mortality: being itself a cautionary tale!

PMID- 16104377
TI  - What do we want to know--a fundamental underwriting question.

PMID- 16104378
TI  - Gene expression differences in mice divergently selected for methamphetamine
      sensitivity.
AB  - In an effort to identify genes that may be important for drug-abuse liability, we
      mapped behavioral quantitative trait loci (bQTL) for sensitivity to the locomotor
      stimulant effect of methamphetamine (MA) using two mouse lines that were
      selectively bred for high MA-induced activity (HMACT) or low MA-induced activity
      (LMACT). We then examined gene expression differences between these lines in the
      nucleus accumbens, using 20 U74Av2 Affymetrix microarrays and quantitative
      polymerase chain reaction (qPCR). Expression differences were detected for
      several genes, including Casein Kinase 1 Epsilon (Csnkle), glutamate receptor,
      ionotropic, AMPA1 (GluR1), GABA B1 receptor (Gabbr1), and dopamine- and cAMP
      regulated phosphoprotein of 32 kDa (Darpp-32). We used the www.WebQTL.org
      database to identify QTL that regulate the expression of the genes identified by
      the microarrays (expression QTL; eQTL). This approach identified an eQTL for
      Csnkle on Chromosome 15 (LOD = 3.8) that comapped with a bQTL for the MA
      stimulation phenotype (LOD = 4.5), suggesting that a single allele may cause both
      traits. The chromosomal region containing this QTL has previously been associated
      with sensitivity to the stimulant effects of cocaine. These results suggest that
      selection was associated with (and likely caused) altered gene expression that is
      partially attributable to different frequencies of gene expression polymorphisms.
      Combining classical genetics with analysis of whole-genome gene expression and
      bioinformatic resources provides a powerful method for provisionally identifying
      genes that influence complex traits. The identified genes provide excellent
      candidates for future hypothesis-driven studies, translational genetic studies,
      and pharmacological interventions.

PMID- 16104379
TI  - Fine mapping of a major locus on chromosome 10 for exploratory and fear-like
      behavior in mice.
AB  - Advanced intercross lines (AIL) and interval-specific congenic strains (ISCS)
      were used to fine map previously coarsely defined quantitative trait loci (QTL)
      on Chromosomes 1, 10, and 19, influencing behaviors in the open Field (OF) and
      light-dark (LD) paradigms in mice. F12(A x B) AIL mice (N = 1130) were
      phenotyped, genotyped, and mapped. The ISCS were studied only in the telomeric
      Chromosome 10 region of interest, containing the exploratory and excitability
      QTL1 (Exq1). The Chromosome 10 Exq1 and Chromosome 19 Exq4 loci mapped robustly
      in the AIL. The most significant QTL findings (2.0 LOD score intervals; peak; LOD
      score) came from the TD15 and LD transitions traits, yielding estimated intervals
      of 2.2 cM for Exq1 (71.3-73.5 cM; peak 72.3 cM; LOD 11.9) and 9.0 cM for Exq4
      (29.0-38.2 cM; peak 34 cM; LOD 4.2). The replicated QTLs on Chromosome 1 failed
      to map in this AIL population. The ISCS data confirmed Exq1 loci in general.
      However, the ISCS data were complex and less definitive for localizing the Exq1
      loci. These exploratory and fear-like behaviors result from inheriting "many
      small things," namely, QTL explaining 2%-7% of the phenotypic variance. These
      results highlight the challenges of positionally cloning loci of small effect for
      complex traits. In particular, fine-mapping success may depend on the genetic
      architecture underlying complex traits.

PMID- 16104380
TI  - Genetic analysis of alcohol intake in recombinant inbred and congenic strains
      derived from A/J and C57BL/6J progenitors.
AB  - The objective of the present study was to map quantitative trait loci (QTL) for
      alcohol intake using A x B/B x A recombinant inbred (RI) and AcB/BcA recombinant
      congenic (RC) strains of mice that were independently derived from the A/J and
      C57BL/6J progenitors. Mice were screened for levels of alcohol consumption with
      four days of forced exposure to alcohol, followed by three weeks of free choice
      between water and a 10% alcohol solution. Alcohol consumption data previously
      collected for 27 A x B/B x A RI strains were reanalyzed using a larger marker set
      and composite interval mapping. The reanalysis found markers on Chromosome 2
      (D2Mit74, 107 cM) (males and females) and on Chromosome 11 (Pmv22, 8 cM) (females
      only) that exceeded the threshold for significant loci, and found suggestive loci
      (in males) on Chromosomes 10 (D10 Mit126, 21 cM), 12 (D12Mit37, 1 cM), 15 (Pdgfb,
      46.8 cM), and 16 (D16Mit125, 29 cM). An additional suggestive locus was
      identified in female RI mice on Chromosome 11 (D11Mit120, 47.5 cM). Composite
      interval mapping (CIM) analysis indicated that there was a significant
      association between loci at Pdgfb and D2Mit74 in both males and females. Analysis
      of the AcB/BcA RC strains identified 11 QTL on Chromosomes 2, 3, 5,6, 7, 8, 9,
      10, 12, 13, and 15. QTL on Chromosomes 7, 10, 12, and 15 were identified in both
      the A x B/B x A RI and AcB/BcA RC strains of mice. Additional QTLs identified on
      Chromosomes 2, 3, 7, 11, and 15 overlap with those previously identified in the
      literature using strains of mice with a C57BL/6J progenitor.

PMID- 16104381
TI  - Genetic and phenotypic analysis of Tcm, a mutation affecting early eye
      development.
AB  - Tcm (total cataract with microphthalmia) is an autosomal dominant mouse eye
      mutation. Heterozygous Tcm/+ mice are born with several eye malformations
      including microphthalmia, retinal and iris dysplasia, total lens cataract, and
      ventral coloboma. The Tcm mutation was previously mapped to a 26-Mb region on Chr
      4 between D4Mit235 and D4Mit106. In this study, we characterize the Tcm/ Tcm
      homozygous mutant and find they are viable but severely microphthalmic. The
      developing eye in the Tcm/Tcm homozygote shows defects during early eye
      development, before formation of the optic cup. Further genetic mapping reduced
      the Tcm critical region to a 1.3-Mb region bordered by SNPs rs3666764 and
      rs3713818. This critical region contains two known genes (Asph and Gfd6) and
      three predicted genes, all of which are positional candidates for Tcm. Sequence
      analysis of Tcm genomic DNA revealed no mutations in the coding regions and
      splice site junctions of the five candidate genes. These results indicate that
      the causitive Tcm mutation falls within a noncoding regulatory region of one of
      the five candidate genes or in an undescribed gene.

PMID- 16104382
TI  - Quantitative trait mapping in a diallel cross of recombinant inbred lines.
AB  - A recombinant inbred intercross (RIX) is created by generating diallel F1 progeny
      from one or more panels of recombinant inbred (RI) strains. This design was
      originally introduced to extend the power of small RI panels for the confirmation
      of quantitative trait loci (QTL) provisionally detected in a parental RI set. For
      example, the set of 13 C x B (C57BL/6ByJ x BALB/cByJ) RI strains can, in
      principle, be supplemented with 156 isogenic F1s. We describe and test a method
      of analysis, based on a linear mixed model, that accounts for the correlation
      structure of RIX populations. This model suggests a novel permutation algorithm
      that is needed to obtain appropriate threshold values for genome-wide scans of an
      RIX population. Despite the combinational multiplication of unique genotypes that
      can be generated using an RIX design, the effective sample size of the RIX
      population is limited by the number of progenitor RI genomes that are combined.
      When using small RI panels such as the C x B there appears to be only modest
      advantage of the RIX design when compared with the original RI panel for
      detecting QTLs with additive effects. The RIX, however, does have an inherent
      ability to detect dominance effects, and, unlike RI strains, the RIX progeny are
      genetically reproducible but are not fully inbred, providing somewhat more
      natural genetic context. We suggest a breeding strategy, the balanced partial
      RIX, that balances the advantage of RI and RIX designs. This involves the use of
      a partial RIX population derived from a large RI panel in which the available
      information is maximized by minimizing correlations among RIX progeny.

PMID- 16104383
TI  - Chocolate coated cats: TYRP1 mutations for brown color in domestic cats.
AB  - Brown coat color phenotypes caused by mutations in tyrosinase-related protein-1
      (TYRP1) are recognized in many mammals. Brown variations are also recognized in
      the domestic cat, but the causative mutations are unknown. In cats, Brown, B, has
      a suggested allelic series, B > b > b1. The B allele is normal wild-type black
      coloration. Cats with the brown variation genotypes, bb or bb1, are supposedly
      phenotypically chocolate (aka chestnut) and the light brown genotype, b1b1, are
      supposedly phenotypically cinnamon (aka red). The complete coding sequence of
      feline TYRP1 and a portion of the 5' UTR was analyzed by direct sequencing of
      genomic DNA of wild-type and brown color variant cats. Sixteen single nucleotide
      polymorphisms (SNPs) were identified. Eight SNPs were in the coding regions, six
      are silent mutations. Two exon 2 on mutations cause amino acid changes. The C to
      T nonsense mutation at position 298 causes an arginine at amino acid 100 to be
      replaced by the opal (UGA) stop codon. This mutation is consistent with the
      cinnamon phenotype and is the putative light brown, b1, mutation. An intron 6
      mutation that potentially disrupts the exon 6 downstream splice-donor recognition
      site is associated with the chocolate phenotype and is the putative brown, b,
      mutation. The allelic series was confirmed by segregation and sequence analyses.
      Three microsatellite makers had significant linkage to the brown phenotype and
      two for the TYRP1 mutations in a 60-member pedigree. These mutations could be
      used to identify carriers of brown phenotypes in the domestic cat.

PMID- 16104384
TI  - A novel polymorphism in the 5' untranslated region of the porcine cytochrome b5
      (CYB5) gene is associated with decreased fat androstenone level.
AB  - Raising intact male pigs would have a significant economic impact on the pork
      industry; however, the presence of 16-androstene (a major cause of boar taint) in
      meat from male pigs would be highly objectionable to consumers. In pigs, a
      positive correlation has been found between cytochrome b5 (CYB5) and production
      of 16-androstene. The search for polymorphism of CYB5 and functional analysis of
      polymorphism found should have an important impact on the efforts to develop
      genetic markers to select for low androstenone levels in fat from pigs. The aim
      of this study was to search the porcine CYB5 gene for mutations, examine its
      expression, identify genetic polymorphisms, and study how a genetic variation in
      this enzyme translates into interindividual variation in androstenone levels in
      fat from pig testis. We have identified a single nucleotide polymorphism (SNP) (G
      --> T) at base 8 up-stream of ATG in the CYB5 5' untranslated region which is
      associated with a lower fat androstenone level. Of the 229 testis samples tested,
      84.8% were homozygous for the variant G, 12.4% were heterozygous, and 2.8% were
      homozygous for the variant T. Functional analysis of this mutation revealed that
      an individual homozygous for the T allele showed significantly lower CYB5
      activity than an individual homozygous for the G allele. Thus, this may be at
      least partially responsible for a lower level of androstenone in pigs. Our
      findings provide an important genetic basis toward the goal of predicting the
      androstenone status in pigs and developing genetic markers for low androstenone.

PMID- 16104385
TI  - On growth, fatness, and form: a further look at porcine chromosome 4 in an
      Iberian x Landrace cross.
AB  - A crossed population between Iberian x Landrace pigs consisting of 321 F2, 87 F3,
      and 85 backcross individuals has been analyzed to refine the number and positions
      of quantitative trait loci (QTL) affecting shape, growth, fatness, and meat
      quality traits in SSC4. A multitrait multi-QTL approach has been used. Our
      results suggest that carcass length and shoulder weight are affected by two loci.
      The first one, close to the AFABP gene, has a very strong pleiotropic effect on
      fatness, whereas the second one, in the interval between S0073 and S0214, also
      affects live weight, although to a lesser extent. This latter QTL would
      correspond to the FAT1 locus described initially in pigs. It seems that SSC4's
      loci play an important role in redistributing total weight, and the Landrace
      allele increases shoulder weight and carcass length much more than ham or total
      weight. Furthermore, there is also strong evidence of additional loci influencing
      pH and color in more distant, telomeric positions.

PMID- 16104386
TI  - An insertion mutation of the bovine Fii gene is responsible for factor XI
      deficiency in Japanese black cattle.
AB  - Factor XI deficiency in Japanese black cattle is an hereditary mild bleeding
      disorder with an autosomal recessive mode of inheritance. To characterize the
      molecular lesion causing factor XI deficiency in cattle, we isolated an entire
      coding region of the bovine F11 gene, which comprises 15 exons and 14 introns,
      and determined its nucleotide sequences. Comparison of the nucleotide sequences
      of the F11 gene between affected and unaffected animals revealed an insertion of
      15 nucleotides in exon 9 of the affected animals. The insertion results in a
      substitution of one amino acid with six amino acids in a highly conserved amino
      acid sequence in the fourth apple domain of factor XI protein. Genotyping of the
      F11 gene in 109 Japanese black cattle revealed that the insertion clearly
      corresponded to the factor XI activities of the animals. We therefore concluded
      that the insertion of 15 nucleotides in the F11 gene is the causative mutation
      for factor XI deficiency in Japanese black cattle. Genotyping of the F11gene by
      detecting the insertion will be an effective DNA-based diagnostic system to
      prevent incidence of the disease.

PMID- 16104387
TI  - [Molecular and biochemical principles of neoplasm enzyme therapy].
AB  - Bacterial enzymes are antineoplastic perspective agents in oncology. Current
      strategy of tumor enzyme therapy is primarily based on the strictly defined
      differences of biochemical properties between normal and tumor cells and more
      precisely on their different sensitivity to deficit of essential growth factors,
      including amino acids. The growth inhibitory effects of three bacterial enzymes:
      glutamine (asparagin)ase, methionine gamma-lyase and lysine alpha-oxidase were
      demonstrated in in vitro and in vivo using several tumor lines. These results
      suggest that commercial production of certified standard enzyme preparations and
      their knowledge-based rational application will provide a new potent anti-tumor
      preparations employed in oncology.

PMID- 16104388
TI  - [Plasminogen activators and thrombolytic therapy].
AB  - The mechanism of plasminogen activation by streptokinase, tissue and urokinase
      type plasminogen activators (PAs) were reviewed. The regulatory role of fibrin in
      plasminogen activation involving its direct interaction with tissue-type PA and
      indirect interaction with streptokinase and urokinase-type PAs was demonstrated.
      Recent information on the development of new PAs is also displayed. The result of
      studies of PA mutant derivatives synthesized by recombinant DNA techniques are
      discussed. Date on chimeric (hybrid) forms of PAs and their chemically
      synthesized conjugates are presented. The trend in search for PAs is analysed. A
      new direction in the study of PAs for combined plasminogen activation and the
      further development of the methods of thrombolytic therapy was outlined.

PMID- 16104389
TI  - [The role of ceruloplasmin in neoplastic processes].
AB  - Ceruloplasmin (CP) is a copper containing oxidase of human plasma alpha 2
      globulin fraction. The review summarizes literature data on biological role of CP
      under normal conditions and during development of malignant tumor. This protein
      may be involved both into antitumor deference and also into metastasizing
      process. Although CP has already been employed into intensive therapy of
      oncologic patients all mechanisms underlying its biological activity remain to be
      clarified.

PMID- 16104390
TI  - [Production and characteristics of PEGylated immunoliposome transport vectors
      specific for neural tissue astrocytes].
AB  - PEGylated (stealth) immunoliposomes covalently linked to antibodies against human
      gliofibrillary acidic protein (GFAP) were prepared by coupling the thiolated
      monoclonal anti-GFAP antibodies, D4, with a maleimide derivative of the
      phosphatidyl ethanolamine of the liposomal membrane. Depending on the initial
      protein-to-lipid ratios, the immunoliposomes prepared (with a diameter of about
      70 nm) were coupled with 60 to 240 molecules of the antibodies. In vitro
      experiments with cultures of the embryonic rat brain astrocytes demonstrated a
      specific binding of these immunoliposomes, which could be inhibited by the
      preincubation of the cells with free non-coupled D4 but not with non-specific
      antibodies. Administered intravenously into rats, the immunoliposomes exhibited a
      kinetic behaviour typical for the PEGylated liposomes: after 24 h, approximately
      20% of the doses injected were still present in the blood; the elimination rate
      constants were 0.05-0.09 h(-1), the elimination half-lives were 8-15 h. With such
      a systemic longevity, as well as with such a specificity, these immunoliposomes,
      non-penetrating through intact blood-brain barrier (BBB), should be useful in
      delivering pharmacological agents to glial brain tumours (which continue to
      express GFAP) or to other pathological loci in the brain with a partially
      disintegrated BBB.

PMID- 16104391
TI  - [Study of antiradical activity of new compounds by chemiluminescence].
AB  - Antioxidative and antiradical properties of a new antioxidant cerebroprotective
      drug, enoxifol (benzimidasole derivative), were compared with mexidol by means of
      three chemiluminescent techniques: luminol autooxidation system, Fe2+-induced
      lipid chemiluminescence and lucigenin-induced chemiluminescence with superoxide
      generation by xanthine-xanthine oxidase system. Enoxifol exhibited higher
      antiradical activity than mexidol. This was shown by suppression of luminol
      radicals and superoxide anion-radical generation. Antioxidant properties of
      enoxifol were also demonstrated by decreasing of Fe2+-induced lipid
      chemiluminescence. The recognized properties of enoxifol influencing
      chemiluminescent processes confirm the results, obtained earlier by means of
      indirect methods of free radical processes study in vitro and in vivo (decrease
      of LPO products, activation of antioxidant enzymes), also can underline its
      pharmacological effects.

PMID- 16104392
TI  - [Chronic morphine intoxication and metabolism of neuroactive amino acids in the
      rat brain].
AB  - The influence of chronic morphine intoxication (for 7, 14 and 21-days) has been
      studied on the contents of neuroactive amino acids (GABA, glutamate, glutamine,
      alanine, aspartate, glycine, taurine) and on the activities of their metabolizing
      enzymes (GABA-transaminase, succinic semialdehyde dehydrogenase, succinic
      dehydrogenase, alanine- and aspartate-aminotransferase) in the rat brain regions:
      cortex, brain stem and cerebellum. We detected the significant decrease of
      glutamate level and the enhancement of GABA and aspartate levels in cortex after
      long-term morphine administration. In brain stem the increase in the contents of
      GABA, glutamine and taurine was noted together with the tendency in attenuation
      of this effect when intoxication was prolonged. The dose-dependent enhancement in
      the levels of glutamate, aspartate and glycine was observed after longer courses
      of morphine administration. In cerebellum the 21-day morphine administration led
      to attenuation of the morphine-induced increase in the contents of GABA,
      glutamate, alanine and glycine.

PMID- 16104393
TI  - [The influence of native ribonucleases and their modified derivatives on the
      functional activity of rat peritoneal macrophages].
AB  - The influence of native, hydrophobized and dimeric forms of ribonucleases (RNAse
      A and RNAse Bacillus intermedius) on the process of phagocytosis and fusion
      between lysosomes and phagosomes in rat macrophages has been studied. The effect
      of native RNAses depends on their concentration: comparatively low concentrations
      (0.5-50 microg ml(-1)) stimulate the phagocytosis and phagosome-lysosome fusion
      whereas high concentrations (above 75 microg ml(-1)) inhibit these processes.
      RNAses modified by surfactant oxanol-KD-6 and dimeric forms of RNAses possess
      only the inhibitory effect, which appears at concentration considerably lower
      than that of native enzymes. The stimulatory effect of native RNAses and the
      inhibitory effect of hydrophobized derivatives do not depend on the catalytic
      activity.

PMID- 16104394
TI  - [Free-radical oxidation and regulation of cytoplasmic NADP-dependent malate
      dehydrogenase in rat cardiomyocytes at norm and under ischemia].
AB  - Experimental ishemia of rat myocardium was accompanied by increase of light sum
      (S) and maximal intensity (Imax) of chemiluminescence, amount of a malonic
      dialdehyde and conjugated dienes in cytoplasmic fraction. The activity of NADP
      dependent malate dehydrogenase (EC 1.1.1.82; NADP-MDH) was 1.6 times higher in
      rat heart under ischemia. NADP-MDH was purified from normal and ischemia-exposed
      rat myocardium. Using NADP-MDH purified enzyme preparations the values of Hill
      coefficient for oxaloacetate (1.83 +/- 0.07 and 1.50 +/- 0.10) and Km for NADPH
      (0.058 +/- 0.003 and 0.096 +/- 0.004 mM) were determined for the enzyme at norm
      and under ischemia respectively. Effects of Fe2+, Ca2+, Cu2+ ions, H2O2, oxidized
      and reduced glutathione, adenine nucleotides influence on functioning of NADP-MDH
      from rat heart at norm and under ischemic conditions have been investigated.

PMID- 16104395
TI  - [Circulating nucleic acids in blood of patients with stomach and colon
      neoplasms].
AB  - Concentrations of extracellular deoxy- and ribonucleic acids in blood plasma and
      cell-surface-bound of blood cells were investigated in healthy donors and
      patients with malignant gastrointestinal tumors. Our results indicate that high
      concentration of extracellular DNA in blood plasma along with decreased level of
      extracellular RNA on the surface of blood cells correlate with development of
      gastrointestinal cancer. Ratio of nucleic acids in plasma to total amount of
      nucleic acids circulated in blood is a characteristic parameter distinguishing
      cancer patients from healthy persons.

PMID- 16104396
TI  - [Interrelationship between platelet nitric oxide production and plasma fibrinogen
      level in emergencies].
AB  - Platelet nitric oxide production has been investigated in patients with thoracic
      and abdominal wounds, thermal trauma, varicose disease, methanol and leponex
      poisoning. There is correlation between absolute platelets nitric oxide
      production and fibrinogen plasma level in these patients. The maximal absolute
      platelets nitric oxide production has been revealed at surgical diseases, and
      minimal has been observed at methanol poisoning. Irrespectively to etiology and
      danger of disease, reliable correlation between absolute platelets nitric oxide
      production and fibrinogen plasma level of these patients is established.
      Consequently platelets nitric oxide production may be important for haemostatic
      processes.

PMID- 16104397
TI  - [Computer search for novel HIV-1 integrase inhibitors].
AB  - HIV-1 integrase is the third enzyme essential for viral replication. It
      represents an attractive target for new anti-HIV drugs. Diketo acids represent
      the most prospective class of integrase inhibitors; one of them (S1360) is
      currently under clinical trials. We prepared the training set containing 90
      diketoacid derivatives and performed re-training of computer program PASS.
      Average accuracy of prediction in LOO cross-validation for HIV-1 integrase
      inhibitors was shown to be 99%. We selected eight new potential HIV-1 integrase
      inhibitors among about the 700,000 substances from the databases of commercially
      available chemicals; anti-integrase activity was found experimentally in two
      selected compounds.

PMID- 16104398
TI  - [Quantum chemical model for prediction of the site of hydroxylation of aromatic
      substances mediated by cytochrome P450].
AB  - An approach based on the oxenoid model of monooxygenase action and semiempirical
      quantum chemical calculations was applied to the prediction of aromatic
      hydroxylation sites of cytochrome P450 substrates. The results were compared with
      experimental data on the metabolism in mammals and human from Metabolite
      database.

PMID- 16104399
TI  - Sustainable water management in rural and peri-urban areas: what technology do we
      need to meet the UN millennium development goals?
AB  - Installation of advanced urban water management systems is one of the most
      important first steps in the attempt to overcome poverty on earth, outbreak of
      diseases, crime and even terrorism. Because world wide application of traditional
      water supply, sewerage and wastewater treatment technology requires financial
      resources which are basically not available within a reasonable short time frame
      novel solutions must be found, developed and implemented. The combination of high
      tech on-site treatment of the various waste streams generated in households,
      enterprises and industrial sites, and reuse of the valuable materials obtained
      from the treatment plants, including the purified water, is one of the options
      which is investigated by various groups of researchers and technology developers,
      nowadays. This concept may help meeting the UN Millennium Development Goals,
      provided people are ready to accept this new way of dealing with household
      wastes. Education is necessary to build up the foundation which modern water
      technology can be based upon. In parallel, tailored modifications are to be
      considered to satisfy the specific demands of local communities. In this context,
      female participation appears to be extremely important in the decision making
      process.

PMID- 16104400
TI  - From conventional to advanced environmental sanitation.
AB  - The basic concept of collecting domestic liquid waste in water-borne sewer
      systems goes back more than 100 years and became in the last century the
      conventional approach to sanitation in urban areas. Over the years, these sewage
      disposal systems had to be successively upgraded by additional sewage treatment
      plants increasing investment, operating and maintenance costs. Although these
      conventional sanitation systems could improve significantly the public health
      situation in those countries who could afford to install and operate them, it is
      highly questionable, if they are economically and ecologically sustainable. The
      large number of people in the developing world who still do not have access to
      adequate sanitation is a clear indication that the conventional approach to
      sanitation is not adapted to the socio-economic condition prevailing in most
      countries of Africa, Asia and Latin America. Advanced environmental sanitation is
      aiming not only to protect public health and the integrity of aquatic ecosystems
      but also to conserve precious freshwater and non-renewable resources. The
      Bellagio Principles and the Household Centred Environmental Sanitation Approach
      (HCES) are suggested as guiding principles and a new approach for planing and
      designing advanced (sustainable) environmental sanitation systems.

PMID- 16104401
TI  - Technology for sustainability: the role of onsite, small and community scale
      technology.
AB  - An overview of available onsite, small and community scale wastewater treatment
      technology shows that it is diverse compared to current technology for
      centralised collection and treatment of wastewater. An analysis of the onsite,
      small and community scale technology for achieving sustainability shows that it
      more conducive to achieving sustainability than the centralised technology. It is
      likely, however, that its application is in remote and rural areas, where the
      technology should be improved and integrated with other technology sectors
      (energy, food production) for improved sustainability. Opportunities exist in new
      urban developments to achieve similar outcomes, but concerted efforts are
      required to demonstrate or showcase sustainability benefits in real situations. A
      huge potential also exists for the use of onsite, small and community scale
      technology in developing countries for achieving the same sustainability
      outcomes. It is likely to succeed if the technology is modified to be of lower
      cost but based on the same science, and that research, development and
      demonstrations in developed countries are shown to be successful.

PMID- 16104402
TI  - Emerging approaches to integrated urban water management: cluster scale
      application.
AB  - Integrated Urban Water Management (IUWM) seeks to extend Water Sensitive Urban
      Design to a total water cycle approach that includes reuse of wastewaters. This
      paper investigates the appropriateness of environmental technologies for
      application at a cluster scale in IUWM. Many environmental technologies are
      economically or physically unsuited to use on a municipal or unit scale. Cluster
      scale is a middle ground that will allow such environmental technologies to
      achieve full potential. The concept of cluster scale and the application of
      environmental technologies at this scale are discussed along with some examples
      of suitable technologies.

PMID- 16104403
TI  - Small scale sanitation technologies.
AB  - Small scale systems can improve the sustainability of sanitation systems as they
      more easily close the water and nutrient loops. They also provide alternate
      solutions to centrally managed large scale infrastructures. Appropriate
      sanitation provision can improve the lives of people with inadequate sanitation
      through health benefits, reuse products as well as reduce ecological impacts. In
      the literature there seems to be no compilation of a wide range of available
      onsite sanitation systems around the world that encompasses black and greywater
      treatment plus stand-alone dry and urine separation toilet systems. Seventy
      technologies have been identified and classified according to the different waste
      source streams. Sub-classification based on major treatment methods included
      aerobic digestion, composting and vermicomposting, anaerobic digestion,
      sand/soil/peat filtration and constructed wetlands. Potential users or suppliers
      of sanitation systems can choose from wide range of technologies available and
      examine the different treatment principles used in the technologies. Sanitation
      systems need to be selected according to the local social, economic and
      environmental conditions and should aim to be sustainable.

PMID- 16104404
TI  - Effective distribution of domestic wastewater effluent between percolation
      trenches in on-site treatment systems.
AB  - On-site treatment systems discharging to groundwater rely on the effective
      distribution of effluent across a percolation area to provide an appropriate
      loading rate for the subsoil. In Ireland, this is achieved in a distribution box
      which splits the effluent evenly between the requisite number of percolation
      pipes. The flow regime experienced at four different distribution boxes was
      monitored continuously over twelve month periods which established that the most
      common flow rates at the distribution unit were in the range 1-4 litres/minute
      for a four to five person dwelling. In addition, the average flow rate from the
      four sites was only 100 litres per person per day, compared to recommended design
      value of 180 litres per person per day. Two distribution boxes were also tested
      in the laboratory to assess their distribution efficiency over a range of loading
      rates. The most commonly installed unit was found to significantly favour two out
      of the four trenches and both units were shown to perform particularly poorly at
      a range of different off-level installation angles. Modifications to the boxes
      were also tested, involving plastic V-notch inserts which were shown to greatly
      improve the hydraulic distribution and make the unit much less sensitive to off
      level installation or subsidence.

PMID- 16104405
TI  - Mathematical modelling of small wastewater treatment plants: power and
      limitations.
AB  - Although mathematical modelling of biological wastewater treatment processes has
      proved to be valuable for large-scale WWTPs (wastewater treatment plants) little
      experience has been acquired in the mathematical modelling of small wastewater
      treatment plants. This paper seeks to evaluate the applicability of mathematical
      modelling on small systems, which are characterized by high fluctuations in
      organic and hydraulic loads and little possibility for control. In order to
      achieve this, the paper examines the different steps in a general modelling
      protocol. One important bottleneck for the general use of mathematical modelling
      of small systems that emerges is the frequent sampling and many analyses needed
      for characterization of the flows while its applicability is limited. On the
      other hand, the determination of the model structure of a small WWTP can be quite
      valuable. Experiments show that tracer tests should include tests with a highly
      varying influent flow rate to spot independent small internal flows as these can
      have a significant impact on the behaviour of peak concentrations throughout the
      system. In addition, the model structure determination can provide useful
      information on dead zones, short-circuiting and mixing behaviour in the plant.

PMID- 16104406
TI  - On-site wastewater management system design and landslide risk assessment.
AB  - On-site wastewater management system design and performance is significant in
      assessing landslide risk in areas with potential for slope instability. Much of
      the development in Pittwater, NSW, local government area is on steep coastal land
      which has a history of slope instability. Concern over cases of poorly performing
      or failing on-site wastewater systems and the recognition that these and newly
      designed systems could be contributory to slope instability has been a factor in
      Pittwater Council, NSW, requiring that landslide risk assessment be undertaken
      for new and amended on-site wastewater management systems in potentially unstable
      areas. This paper describes the wastewater management system design and landslide
      risk assessment undertaken at Pittwater Youth Hostel in accordance with the
      Australian Geomechanics Society's Geotechnical Risk Management procedure to
      comply with the Pittwater Policy. The work completed illustrates both necessary
      and effective interaction of the wastewater and geotechnical professions to
      achieve a successful outcome for the client. It is likely that this professional
      interaction will be increasingly common along the NSW coast and elsewhere.

PMID- 16104407
TI  - Parameter investigation for decentralised dewatering and solar thermic drying of
      sludge.
AB  - The purpose of this paper is an experimental and model assisted investigation of
      the capabilities of a dewatering system for sewage sludge for decentralised
      sites. Laboratory and field tests are performed with different initial conditions
      and the influences of filter medium, initial height, initial total suspended
      solids, temperature and relative humidity are discussed. The experimental work
      shows the feasibility of geotextile media for dewatering high water content
      sewage sludge and that the textile structure is of secondary importance. The
      specific filter resistance of the sludge cake is found to be the most significant
      factor in dewatering applications. The mathematical description of the dewatering
      process is based on the superposition of two models, the Conventional Filtration
      Theory for the filtration phase and the BT-model for the drying phase.
      Feasibility and limits of the theoretical approach are evaluated by means of a
      comparison between measurements and simulated data of cyclic reloading tests. It
      is found that a better filtration efficiency is achieved at higher TSS and at
      lower initial height of the slurry layer. Due to the viscosity decrease, a higher
      temperature enhances not only evaporation, but also filtration rate.

PMID- 16104408
TI  - Integrated airlift bioreactor system for on-site small wastewater treatment.
AB  - An integrated airlift bioreactor system was developed, which mainly consists of a
      multi-stage loop reactor and a gas-liquid-solid separation baffle and possesses
      dual functions as bioreactor and settler. This integrated system was used for on
      site treatment of industrial glycol wastewater in lab-scale. The strategy of
      gradually increasing practical wastewater concentration while maintaining the co
      substrate glucose wastewater concentration helped to accelerate the microbial
      acclimation process. Investigation of microbial acclimation, operation parameters
      evaluation and microbial observation has demonstrated the economical and
      technical feasibility of this integrated airlift bioreactor system for on-site
      small industrial wastewater treatment.

PMID- 16104409
TI  - Enhancement of oxygen transfer and nitrogen removal in a membrane separation
      bioreactor for domestic wastewater treatment.
AB  - Biological nitrogen removal in a membrane separation bioreactor developed for on
      site domestic wastewater treatment was investigated. The bioreactor employed
      hollow fiber membrane modules for solid-liquid separation so that the biomass
      could be completely retained within the system. Intermittent aeration was
      supplied with 90 minutes on and off cycle to achieve nitrification and
      denitrification reaction for nitrogen removal. High COD and nitrogen removal of
      more than 90% were achieved under a moderate temperature of 25 degrees C. As the
      temperature was stepwise decreased from 25 to 5 degrees C, COD removal in the
      system could be constantly maintained while nitrogen removal was deteriorated.
      Nevertheless, increasing aeration supply could enhance nitrification at low
      temperature with benefit from complete retention of nitrifying bacteria within
      the system by membrane separation. At low operating temperature range of 5
      degrees C, nitrogen removal could be recovered to more than 85%. A mathematical
      model considering diffusion resistance of limiting substrate into the bio
      particle is applied to describe nitrogen removal in a membrane separation
      bioreactor. The simulation suggested that limitation of the oxygen supply was the
      major cause of inhibition of nitrification during temperature decrease.
      Nevertheless, increasing aeration could promote oxygen diffusion into the bio
      particle. Sufficient oxygen was supplied to the nitrifying bacteria and the
      nitrification could proceed. In the membrane separation bioreactor, biomass
      concentration under low temperature operation was allowed to increase by 2-3
      times of that of moderate temperature to compensate for the loss of bacterial
      activities so that the temperature effect was masked.

PMID- 16104410
TI  - Particle and microorganism removal in floating plastic media coupled with
      microfiltration membrane for surface water treatment.
AB  - Floating plastic media followed by hollow fiber microfiltration membrane was
      applied for surface water treatment. The performance of the system in terms of
      particle and microorganisms was investigated. The floating filter was examined at
      different filtration rates of 5, 10 and 15 m3/m2 x h. Treated water was then fed
      into a microfiltration unit where different filtration rates were examined at
      0.6, 1.0 and 1.4 m3/m2 x d. It was found that polyaluminum chloride was the best
      coagulant for the removal of particle, algae and coliform bacteria. Average
      turbidity in treated water from the floating plastic media filter was 3.3, 12.2
      and 15.5 NTU for raw water of 80 NTU and 12.9, 11.7 and 31.2 NTU for raw water of
      160 NTU after 6 hours at the filtration rates of 5, 10 and 15 m3/m2 x h,
      respectively. The microfiltration unit could further reduce the turbidity to 0.2
      0.5 NTU with low transmembrane pressure development of 0.3-3.7 kPa.
      Microfiltration membrane could retain most of algae and coliform bacteria
      remaining in the effluent from the pretreatment unit. It was found that at higher
      turbidity, algae and coliform bacteria removal efficiencies were achieved at
      lower filtration rate of the system of 5 m3/m2 x h whereas a higher filtration
      rate of 15 m3/m2 x h yielded better coliphage removal.

PMID- 16104411
TI  - Pilot-testing an alternative on-site wastewater treatment system for small
      communities and its automatic control.
AB  - The pilot test of a new alternative for small wastewater treatment system has
      been conducted for two years. It consists of a hybrid bioreactor and the expert
      system including the programmable logic controller and human-machine interface.
      In order to monitor its status, the real-time data was transferred from the
      remote station to the central station via a wireless local area network. More
      efficient and stable performances were observed at automatic operating mode
      compared with the manual. On an average, COD, SS, T-N and T-P concentrations in
      the effluent from the hybrid bioreactor were less than 14, 7, 12 and 0.9 mg/L,
      respectively. According to the result from laboratory experiments, the quality of
      treated wastewater with chemical coagulation process followed by sand filtration
      was enough to be utilized again if a final disinfection step is included.

PMID- 16104412
TI  - Optimal maintenance of constructed wetlands using an environmental decision
      support system.
AB  - Constructed wetlands (CWs) are artificial wastewater treatment systems
      appropriate for small communities because of their affordability, operability and
      reliability. These qualities are true whenever CWs are designed and constructed
      properly, and as long as the necessary operation and maintenance procedures are
      carried out correctly. Experience shows that the operation and maintenance
      procedures, and the frequencies with which these procedures are carried out,
      differ from one CW to another. With this in mind, and along with a projected
      increase in CWs in Catalonia, the Catalan Water Agency (Agencia Catalana de
      l'Aigua) has developed an Environmental Decision Support System (EDSS) which
      proposes guidelines for monitoring and maintenance, according to the
      characteristics of each CW. This EDSS was developed following a methodology based
      on five steps: (i) problem analysis; (ii) collecting data and knowledge
      acquisition; (iii) model selection; (iv) model implementation and (v) validation.
      This paper describes the methodology followed to build the decision support
      system and presents some examples of the information provided by this EDSS.

PMID- 16104413
TI  - Subsurface flow reedbeds using alternative media for the treatment of domestic
      greywater in Monteverde, Costa Rica, Central America.
AB  - This paper describes the performance of reedbeds using plastic (PET) bottle
      segments as an alternative low-cost media for the treatment of domestic greywater
      in Monteverde, Costa Rica, Central America. Twelve reedbeds consisting of four
      sets of triplicates were monitored through wet and dry seasons in order to
      determine the effect of media type (PET versus crushed rock) and the effect of
      plants. In both seasons, performance of the planted reedbeds with PET media, for
      BOD and fecal coliform removal, was either comparable to, or better than, that of
      the crushed rock systems. The planted PET reedbeds achieved fecal coliform
      removal rates > 99.9% in all cases equating to reductions of between 3 and nearly
      5 log, with an average BOD outflow of 12.9 mg/L over both seasons. The hydraulic
      loading rate varied between 1.33 and 2.67 cm/day and hydraulic retention times
      (HRT) ranged from 3.5 to 7.5 days. The six reedbeds planted with Coix lacryma
      jobi proved to be significantly more effective in pathogen removal and BOD
      reduction than the unplanted reedbeds. The planted PET reedbeds also increased
      their biomass by twice that of the planted crushed rock reedbeds during the study
      period. The majority of this increase was shown to be due to root growth. This
      paper discusses the implications of the above results for developing countries
      and identifies potential areas for further research.

PMID- 16104414
TI  - Aspects of design, structure, performance and operation of reed beds--eight
      years' experience in northeastern New South Wales, Australia.
AB  - Reed beds (horizontal subsurface flow constructed wetlands) have been employed as
      secondary treatment devices in on-site and decentralised wastewater management
      systems in the northeast of the Australian state of New South Wales (NSW) for
      over a decade. This paper summarises some of the practical and research findings
      that have come to light in that time. Experience with various aspects of reed bed
      structure is discussed. A study of the evaporative performance of four small beds
      planted with Phragmites australis yielded an annual crop factor of 2.6. A total
      of 28 studies on reed beds treating a variety of commonly encountered wastewater
      streams yielded the following mean pollutant removal efficiencies: total
      suspended solids (TSS) 83%, biochemical oxygen demand (BOD) 81%, total nitrogen
      (TN) 57%, total phosphorus (TP) 35% and faecal coliforms (FC) 1.9 logs. The reed
      bed is becoming the preferred on-site technology for removing TN and BOD and
      polishing TSS from primary settled domestic wastewater. Sizing beds for a
      residence time of approximately five days has become standard practice. A study
      of six reed beds found six different species of earthworm present, mainly
      Perionyx excavatus (Indian Blue). A mesocosm experiment subsequently showed that
      the worms were translocating clogging material from the substrate interstices to
      the surface of the bed thereby indicating a possible method for prolonging reed
      bed life.

PMID- 16104415
TI  - Treatment of high strength wastewater with vertical flow constructed wetland
      filters.
AB  - The aim of the present study was to evaluate the behaviour of vertical flow
      constructed wetlands to treat high strength wastewater. Influents were obtained
      mixing tap water with different percentages of MSW landfill leachate (5%, 10% and
      20%). Phragmites australis seedlings were used as macrophytes. The reeds were
      nurtured during three spring months, before the start of the experimental period.
      Three and four days of detention time were adopted. Influent concentrations of
      510-2,050 mg L(-1), 180-740 mg L(-1) and 65-260 mg L(-1) were obtained for COD, N
      NH4(+) and N-NO3(-), respectively. The environmental temperature averaged around
      31.0 +/- 1.4 degrees C. During the experimental period, all parameters showed an
      increasing removal efficiency trend. Best results in terms of COD removal were
      obtained for mixtures at lowest rate of landfill leachate; while, denitrification
      process showed an opposite behaviour; finally, the removal of ammonia nitrogen
      appeared to be independent upon influent concentrations. Analysis carried out on
      the reed tissues showed a theoretic maximum storage of TKN in the leaves of about
      55 mg/g dry weight. A leachate percentage of about 35% was derived to be able to
      fully inhibit the growth of macrophytes.

PMID- 16104416
TI  - Requirements and test methods for on site domestic wastewater treatment plants:
      the European standard (prEN 12566-3) compared to other international standards.
AB  - To ensure that domestic wastewater treatment plants run in an efficient and
      reliable way, certifications already exist while others will be implemented soon.
      To date, we have listed eight standards: four from European countries (Germany,
      Great Britain, The Netherlands and Norway), one project from the European Union,
      two from North America (USA and Quebec) and one from Australia and New Zealand
      together. The European procedure includes verification of structure stability,
      water tightness and treatment capacity at test centre (38 weeks). The American
      Standard sets minimal standards for materials, dimensioning, building and
      performances of the plants. It also highlights the information and minimum
      service that should be provided by the manufacturer and distributors. The review
      process relating to treatment performances shares major similarities with the EU
      project since both documents were elaborated almost simultaneously. Australia and
      New Zealand have adopted a series entitled On-site Domestic Wastewater Treatment
      Units made up of three parts. The third one integrates construction requirements
      and describes quite an interesting procedure to efficiently test the small plant:
      after approximately 13 weeks of testing (half the total duration), the aeration
      chamber (provided it exists) is filled with sludge from septic tanks to simulate
      its operation after several years. Overview of the treatment efficiency test
      procedures of the three main standards is given.

PMID- 16104417
TI  - Microbiological studies of an anaerobic baffled reactor: microbial community
      characterisation and deactivation of health-related indicator bacteria.
AB  - This WRC funded project has studied the appropriateness of the ABR (anaerobic
      baffled reactor) for on-site primary sanitation in low-income communities. A
      3,000 L pilot reactor was located at the Kingsburgh wastewater treatment plant
      south of Durban, South Africa. Feed to the reactor was raw domestic wastewater
      containing a significant proportion of particulate organic matter. The
      compartments of the ABR were routinely monitored for pH, COD, and gas production,
      among other physical-chemical determinants. The microbial population in each
      compartment was analysed by fluorescent in situ hybridisation, using general
      oligonucleotide probes for eubacteria and archeae and a suite of 10 genera or
      family specific probes. Scanning electron microscopy was conducted on the sludge
      fraction of each compartment. Mixed fractions from each compartment were also
      analysed for health-related indicator bacteria (total coliforms and E. coli).
      Results indicated that methanogenesis was not occurring to the expected extent in
      the latter compartments, and that this was probably due to a hydraulic load
      limitation. This contrasted with earlier studies on industrial effluent, for
      which the organic load was exclusively in soluble form. Inactivation of health
      related indicator bacteria was less than 1 log, indicating the need for an
      additional post-treatment of the effluent to protect community health.

PMID- 16104418
TI  - Effluent quality from 200 on-site sewage systems: design values for guidelines.
AB  - The quality of effluent from an on-site sewage treatment system is a critical
      factor in designing the disposal area and, hence, ensuring the sustained
      performance of the system. Contaminant concentrations in effluent are typically
      specified in regulatory guidelines or standards; however, the accuracy of these
      guideline values are brought into question due to the poor performance of septic
      tanks and the high failure rates of disposal systems reported here and elsewhere.
      Results from studies of septic tank effluent quality indicated that the effluent
      is of poorer quality than currently suggested by guidelines. Aerated wastewater
      treatment systems were found to perform to accreditation guidelines; however,
      insufficient nutrient data is presently available to assess nutrient loads. It is
      proposed that the 80th percentile of system performance be adopted as the design
      value for sizing effluent disposal areas to minimise failure associated with
      overloading. For septic tanks this equates to 660 mg L(-1) SS, 330 mg L(-1) BOD,
      250 mg L(-1) TN and 36 mg L(-1) TP.

PMID- 16104419
TI  - Monitoring of the process of composting of kitchen waste in an institutional
      scale worm farm.
AB  - Vermicomposting provides an alternative method of managing waste that is
      ecofriendly and cost-effective. The Environmental Technology Centre (ETC) at
      Murdoch University and St. John of God Hospital (SJOG) signed a Memorandum of
      Understanding (MOU) to install a vermiculture system in SJOG to treat some of the
      organic waste generated by the on site kitchen facility. This is an effort made
      by SJOG to reduce the amount of organic waste sent to landfill each year and to
      treat the waste on site as part of a recycling/reuse program. The study is aimed
      at scientifically monitoring vermicomposting process and to understand the
      optimum management requirements to improve the operation of an institutional
      scale worm farm. In addition, an experiment was conducted to investigate the
      suitability of bedding materials: horse manure, cow manure, peat coir, and
      natural bedding (vermicast). The species of earthworms used in this experiment
      were Red (Lumbricus rubellus), Tiger (Eisenia fetida), and Blue (Lumbricus
      excavatus). The pH, temperature, worm population and quality of castings were
      tested in different beds. Results indicated that vermicast was the best bedding
      for vermicomposting, and there were no significant difference between the
      performances of the other three beds. However, it can be concluded that the
      bedding material of horse manure, cow manure, and peat coir were successfully
      established well within the experimental period of eight weeks, and cow manure
      with the lowest C:N ratio produced the best quality bedding. As using vermicast
      for the initial bedding creates a very high capital cost these organic substrates
      provide cost-effective alternative. Therefore they would be quite appropriate to
      initiate an institutional scale worm farm.

PMID- 16104420
TI  - Evaluating the application of a decision support system in identifying adequate
      wastewater treatment for small communities. A case study: the Fluvia River Basin.
AB  - The identification of adequate wastewater treatment for small communities is a
      complex problem since it demands a combination of data from different sources,
      such as aspects of the community and landscape, the receiving environment and the
      available wastewater treatment technologies. The Catalan Water Agency (Agencia
      Catalana de l'Aigua) considered using an EDSS (Environmental Decision Support
      System) as a tool to help water managers select the most adequate treatment for
      the urban wastewater of nearly 3,500 small communities in Catalonia (Spain). From
      that moment, EDSS was applied to all the river basins in Catalonia. In this paper
      the authors present the results obtained for the 76 small communities located in
      one of these river basins: the Fluvia River Basin. The characteristics of the
      community used in the reasoning process of the EDSS, the list of selected
      wastewater treatment alternatives, the technical environmental justification for
      the selected treatments and the reasons for discarding, favouring or
      disadvantaging them are presented. Finally, some results for the Fluvia River
      Basin are compared with those obtained in other Catalan river basins with
      different characteristics in order to evaluate which are the significant features
      in identifying adequate wastewater treatments.

PMID- 16104421
TI  - On-site greywater treatment and reuse in multi-storey buildings.
AB  - The paper presents a study of a pilot plant treating light greywater for seven
      flats. The pilot plant combines biological treatment (RBC) with physicochemical
      treatment (sand filtration and disinfection). The pilot plant produced effluent
      of excellent quality, meeting the urban reuse quality regulations, and was very
      efficient in TSS turbidity and BOD removal: 82%, 98% and 96%, respectively. COD
      removal was somewhat lower (70-75%) indicating that the greywater may contain
      slowly-biodegradable organics. The RBC (attached growth biological system) was
      able to retain most of the solids as a result of bioflocculation; further it was
      proven to have very stable and reliable performance. Faecal coliforms and
      heterotrophic reductions were very high (100% and 99.99%, respectively) producing
      effluent that also met drinking water standards. The combination of low organic
      matter, nutrients and microbial indicators reduces the regrowth and fouling
      potentials in the reuse system, thus ensuring safe reuse of the treated greywater
      for toilet flushing.

PMID- 16104422
TI  - Research on wastewater reuse planning in Beijing central region.
AB  - The need to implement wastewater reuse in Beijing is discussed. Based on the
      investigation of the built wastewater reuse projects in Beijing, the differences
      between small wastewater reuse system and large systems were analyzed according
      to the technical, economical and social issues. The advantages and disadvantages
      of the small system and the large system were then given. In wastewater reuse
      planning in Beijing urban region, the large system was adopted. The rations of
      reclaimed water for difference land use type, including industrial reuse,
      municipal reuse, grass irrigation, and scenes water reuse were determined. Then
      according to the land use information in every block in central Beijing, using
      GIS techniques, the amounts of the reclaimed water needed in every block were
      calculated, and the main pipe system of reclaimed water was planned.

PMID- 16104423
TI  - Greywater recycling systems in Germany--results, experiences and guidelines.
AB  - Although Germany is not considered a water-poor country, there exist regional
      differences in water supply and consumption. During the past 15 years, the
      greywater aspect has been dealt with in Germany with a greater interest and
      variable success. In addition to an increased environmental awareness, water
      costs also play an important role in increasing the demand for advanced greywater
      treatment plants nstalled in buildings. Under favourable conditions, the
      amortisation costs usually lie between 5 and 7 years. Systems that have been
      extensively tried and tested and have been shown to be most reliable are those
      employing an advanced biological treatment followed by an UV disinfection.
      Systems based on membrane technology are being developed and researched
      intensively in Germany for municipal wastewater treatment. However, so far they
      play no role in greywater recycling. Greywater systems operating under low energy
      and maintenance requirements without the use of chemicals are mostly favoured. In
      Germany, greywater recycling systems should be registered at the Health Office in
      order to guarantee that no cross-connections exist with the drinking water
      network and that pipes are labelled according to regulations. The hygienic
      requirements for recycled greywater, which is primarily used for toilet flushing,
      are oriented towards the EU-Guidelines for Bathing Waters. The use of recycled
      greywater for irrigation purposes is minor. As to the use of recycled water for
      laundry, the first promising investigation results are now available.

PMID- 16104424
TI  - Recycling of treated domestic effluent from an on-site wastewater treatment
      system for hydroponics.
AB  - An alternative method to conserve water and produce crops in arid regions is
      through hydroponics. Application of treated wastewater for hydroponics will help
      in stripping off nutrients from wastewater, maximising reuse through reduced
      evaporation losses, increasing control on quality of water and reducing risk of
      pathogen contamination. This study focuses on the efficiency of treated
      wastewater from an on-site aerobic wastewater treatment unit. The experiment
      aimed to investigate 1) nutrient reduction 2) microbial reduction and 3) growth
      rate of plants fed on wastewater compared to a commercial hydroponics medium. The
      study revealed that the chemical and microbial quality of wastewater after
      hydroponics was safe and satisfactory for irrigation and plant growth rate in
      wastewater hydroponics was similar to those grown in a commercial medium.

PMID- 16104425
TI  - Nutrient reduction evaluation of sewage effluent treatment options for small
      communities.
AB  - Small communities that are sewered by either package sewage treatment plants or
      on-site sewerage facilities are finding that the ground and surface waters are
      being contaminated. Nitrogen, which typically is not removed in these
      conventional systems, is a major concern. This project evaluated the capability
      of four sewage treatment technologies to reduce the amount of nitrogen being
      discharged in the effluent to the receiving environment. The four sewage
      treatment processes evaluated include a recirculating sand filter, biofilter,
      slow sand filter and constructed subsurface flow wetland. These processes were
      evaluated for their capability to reduce nitrogen, phosphorus, BOD5 and TSS. The
      primary objective of the project was to evaluate the capability of these
      treatment processes to reduce nitrogen using biological processes nitrification
      and denitrification. This paper reports on the performance of these processes to
      reduce nitrogen. The study demonstrated that the biofilter was capable of
      removing from a primary treated influent 40% of the total nitrogen. For the same
      quality influent the recirculating sand filter was capable of removing 35% of the
      total nitrogen. Secondary treated effluent was fed to the slow sand filter and
      the subsurface flow wetland. There was a 52% reduction in total nitrogen through
      the wetland however there was virtually no reduction in total nitrogen through
      the slow sand filter.

PMID- 16104426
TI  - Evaluation of bipolar electrocoagulation applied to biofiltration for phosphorus
      removal.
AB  - To reduce the residual organic matter and phosphorus contained in secondary
      effluent, a biofiltration system combined with electrocoagulation using bipolar
      iron electrodes was evaluated as a supplementary treatment to existing small
      community sewage treatment. Based on the results of batch tests, bipolar
      electrocoagulation (BEC) was found to be more effective on phosphorus removal
      than monopolar electrocoagulation (MEC) but energy consumption was less in
      monopolar electrocoagulation. Optimum conditions of BEC to treat the secondary
      effluent were current density 15 A/m2, electrode spacing 1 cm and pH < 8. The
      removals of COD(Cr) and phosphorus by biofiltration system without BEC were 69.1%
      and 9.6%, respectively. However, biofiltration system combined with BEC showed
      76.6-83.7% and 70.7-93.0% removal for COD(Cr) and phosphorus respectively.
      Extraordinary increase in phosphorus could be achieved by introducing
      electrocoagulation to biofiltration, and BEC/biofiltration system was evaluated
      to be applicable to existing small-community sewage treatment plants as a
      supplementary process.

PMID- 16104428
TI  - Application of remote monitoring and automatic control system using neural
      network for small wastewater treatment plants in Korea.
AB  - For this study, an automatic control system has been developed by using a neural
      network and internet-based remote monitoring system for efficient operation of
      plants that have a serious variance of influent loading and have difficulties in
      appropriate maintenance, just like small wastewater treatment plants in Korea. In
      the control algorithm, ORP was used as the main sensor for control. At the point
      where the ORP value was judged to reach the "nitrate knee" of denitrification and
      phosphorus release, ORP indicated the state of lower saturation read by the
      neural network and then changed the operating condition from the reduction state
      to the oxidation state. For example, if ORP indicates the state of higher
      saturation at the point of "nitrogen breakpoint" or "ammonia valley" of
      nitrification, the neural network reads it and cuts off the oxygen supply and
      mixing. The dORP data have been used as one of the main input for the neural
      network. After the operation of lab-scale cyclic aeration process using an
      automatic control system, it has been found that regardless of loading variance,
      more than 95% of organic matters and more than 60% of nitrogen and phosphorus
      have been removed. Assuming that an internet-connected computer and a basic web
      browser are available, this study has developed a remote monitoring system that
      can monitor the operating status of small plants or any troubles with them.

PMID- 16104427
TI  - Effect of internal recycle rate on the high-strength nitrogen wastewater
      treatment in the combined UBF/MBR system.
AB  - An anaerobic/aerobic system combining an anaerobic upflow-sludge bed filter (UBF)
      and an aerobic membrane bioreactor (MBR) was operated to enhance organic and
      nitrogen removal efficiency. The internal recycle rate, which is one of the most
      important operation factors that affects overall removal efficiency, was varied
      from 100% to 300% of the influent flow. Under these conditions, the overall
      removal efficiencies of organic and nitrogen and characteristics of membrane
      fouling in the combined system treating the synthetic wastewater including high
      concentration of organics and nutrients were studied. As a result, nitrogen
      removal efficiency was increased to 67% when the internal recycle rate was 300%
      of influent flow rate. As the internal recycle ratio increased from 100% to 200%,
      protein content decreased by 17% and carbohydrate content increased by 12%.
      However, there was no remarkable difference in total extracellular polymeric
      substances (EPS) content. At the high recycle rate of 300%, the surface charge of
      sludge was decreased while hydrophobicity (specific ultraviolet absorbance, SUVA)
      was increased. The differences in SUVA and surface charge were 11% and 1%,
      respectively. It is concluded that SUVA and EPS composition were important
      parameters affecting membrane fouling in the combined system.

PMID- 16104429
TI  - The effect of nitrogen loading on on-site system design: a model for determining
      land application area size.
AB  - Designers of on-site wastewater management systems have six opportunities to
      remove pollutants of concern from the aqueous waste stream before it reaches
      ground or surface waters. These opportunities occur at source, at point of
      collection (primary treatment), secondary treatment, tertiary treatment, land
      application and buffers. This paper presents a computer based model for the
      sizing of on-site system land application areas applicable to the Lismore area in
      Northern New South Wales, a region of high rainfall. Inputs to the model include
      daily climatic data, soil type, number of people loading the system and size of
      housing allotment. Constraints include allowable phosphorus export, nitrogen
      export and hydraulic percolation. In the Lismore area nitrogen is the nutrient of
      most concern. In areas close to environmentally sensitive waterways, and in dense
      developments, the allowable annual nitrogen export becomes the main factor
      determining the land application area size. The model offers system designers the
      opportunity to test various combinations of nitrogen attenuation strategies
      (source control, secondary treatment) in order to create a solution which offers
      an acceptable nitrogen export rate while meeting the client's household and
      financial needs. The model runs on an Excel spreadsheet and has been developed by
      Lismore City Council.

PMID- 16104430
TI  - Evaluation of recirculating sand filter in a cold climate.
AB  - Approximately 30% of Minnesota's residents rely on onsite technologies for their
      wastewater treatment. There is a growing need for 'alternative' technologies to
      aid in treatment for difficult sites and sensitive environmental areas.
      Recirculating sand filters (RSFs) have been used since the 1970s for small
      communities with flows > 20,000 L per day, but use for small flow application (<
      5,000 L/d) has been growing due to its small land use requirement. A research
      site was developed in southern Minnesota in 1995 to test alternative
      technologies, including two RSFs. In addition, in 1998, two RSFs were added to
      existing residential soil treatment systems that were having problems because of
      inadequate separation and fill soil conditions. All RSFs in this study used 0.6
      metres of coarse sand for treatment, were loaded at approximately 204 L per day
      per square metre (5 gallons per square foot per day) and a recirculation rate of
      5:1. All RSFs have effectively reduced Biochemical Oxygen Demand (BOD5), Total
      Suspended Solids (TSS), Fecal Coliform (FC) and Nutrients (nitrogen and
      phosphorus). These systems are able to achieve secondary effluent treatment
      levels for BOD5 and TSS. The median FC reduction was 90% with a value of 5.7 E4
      cfu/100 mL, indicating additional treatment is necessary to protect health and
      the environment. The RSFs consistently removed 25% or more total phosphorus (TP)
      and 40% or more total nitrogen (TN). The RSFs did not show significantly
      decreased performance during the winter months. Two of the RSFs receiving rather
      high strength domestic waste were able to reduce a greater percentage of total
      nitrogen, indicated that the addition of carbon from the high strength waste is a
      benefit resulting in greater TN removal.

PMID- 16104431
TI  - An overview of the Central Queensland University self-contained
      evapotranspiration beds.
AB  - The Central Queensland University (CQU) has championed a self-contained concrete
      lined evapotranspiration channel. Any non-transpired effluent returns to a
      holding tank and is recirculated through the evapotranspiration channel until it
      is used. This paper examines the results from the Rockhampton trial site.
      Nutrient ions in the effluent were quantified over time and found not to
      accumulate in solution. Microbial analysis of the treated effluent was performed
      and was found to be within the ranges required by the relevant legislative codes.
      Citrus fruit grown in the evapotranspiration channel were sampled and no elevated
      levels of faecal coliforms were recorded. Macronutrients and micronutrients of
      the soil in the channels were measured over a 5-year period. No toxic
      accumulations or nutrient deficiencies in the soil occurred. Levels of salinity
      and sodicity in the evapotranspiration channel soil were quantified. Salinity
      rose slightly, as did sodium. Concentrations of salts and sodium did not reach
      unsustainable levels. The aim of the trial was to develop an on-site treatment
      and reuse system that is sustainable and protects public and environmental
      health.

PMID- 16104432
TI  - Effluent tracing and the transport of contaminants from a domestic septic system.
AB  - A domestic soil absorption system in a coastal location was instrumented with
      suction lysimeters and piezometers and monitored between August and December
      2002. Using the sandy soils from the site, column leaching experiments were also
      undertaken and these suggested that bromide would be a suitable conservative
      tracer which could be added to the wastewater system to determine the direction
      and rate of groundwater flow. The septic system plume boundaries were identified
      from the monitoring results and the subsurface fate of the inorganic nutrients
      determines using ion ratios. The tracing results indicated that groundwater was
      moving at 0.4 m/day towards a nearby drain. The ion ratios indicated that total
      inorganic nitrogen and orthophosphate were not substantially lost or diluted in
      the sandy soils downgradient from the soil absorption system, and that without
      riparian vegetarian lining the drain, these nutrients would have been largely
      unattenuated in transport. In the absence of adequate vertical and horizontal
      setback distances, riparian vegetation is regarded as very important in limiting
      the subsurface transport of inorganic nutrients from domestic septic systems.

PMID- 16104433
TI  - Hydrogen sulphide production tests and the detection of groundwater faecal
      contamination by septic seepage.
AB  - The 'H2S test' is being advanced for microbiological water quality testing where
      conventional coliform based methods are impractical or too expensive. It involves
      ambient temperature incubation of water samples with nutrient formulated to
      generate hydrogen sulphide when 'faecal' bacteria are present. Recently a WHO
      review identified several concerns including the limited number of comparative
      studies, formulation variability, and false positives and negatives. In response
      we have compared the H2S test's ability to detect and quantify faecal
      contamination in an aquifer impacted by septic tank leachfields with measurements
      obtained concurrently using conventional bacterial indicators, coliphages, faecal
      sterol biomarkers, Cryptosporidium and Giardia. Like these other analytes, H2S
      testing detected a contamination gradient ranging from high (septic liquid) to
      moderate (exfiltration zones), to background (e.g. domestic bores), corresponding
      to indicator removal + dilution by factors > 10(6). Presence/absence tests could
      not distinguish between heavily and slightly contaminated waters, whereas multi
      tube testing (e.g. 10 x 10 mL arrays) did. It was concluded that while the WHO
      review concerns are justified, the H2S test performance shows promise in sanitary
      survey work, can be improved by employing an mpn approach and has potential to
      aid in the protection of source water and identifying contaminated groundwater.

PMID- 16104434
TI  - Equalization characteristics of an upflow sludge blanket-aerated biofilter (USB
      AF) system.
AB  - Equalization characteristics of the upflow sludge blanket-aerated bio-filter (USB
      AF) were investigated with the fluctuated raw domestic sewage. Recycle of
      nitrified effluent from AF to USB triggered the equalization characteristics of
      the sludge blanket on both soluble and particulate organic matter. Increment of
      EPS in sludge blanket by nitrate recycle was detected and removal of turbidity
      and particulates increased at higher recycle ratios by bio-flocculation.
      Increased TCOD removal in the USB was due to both denitrification of recycled
      nitrate and entrapment of the particulate organic matter in sludge blanket.
      Capture of both soluble and particulate organic matter increased sludge blanket
      layer in the USB, which improved the reactor performances and reduced the organic
      load on the subsequent AF. Overall TCOD and SS removal efficiencies were about
      98% and 96%, respectively in the USB-AF system. Turbidity in the USB effluent was
      about 44, 20 and 5.5 NTU, at recycle ratios of 0, 100 and 200%, respectively.
      Particle counts in the range 2-4 microm in the USB effluent were higher than
      those in influent without nitrate recycle, while particle counts in the range of
      0.5-15 microm in the USB effluent decreased 70% at recycle ratio of 200%. The
      major constituent of EPS extracted from anaerobic sludge was protein and total
      EPS increased from 109.1 to 165.7 mg/g-VSS with nitrate recycle of 100%. Removal
      efficiency and concentration of T-N in the UBS-AF effluent was over 70% and below
      16 mg/L, respectively.

PMID- 16104435
TI  - On-site treatment of a motorway service area wastewater using a package
      sequencing batch reactor (SBR).
AB  - A sequencing batch reactor (SBR) treating the effluent of a motorway service
      station in the south of England situated on a major tourist route was
      investigated. Wastewater from the kitchens, toilets and washrooms facilities was
      collected from the areas on each side of the motorway for treatment on-site. The
      SBR was designed for a population equivalent (p.e.) of 500, assuming an average
      flow of 100 m3/d, influent biochemical oxygen demand (BOD) of 300 mg/l, and
      influent suspended solids (SS) of 300 mg/l. Influent monitoring over 8 weeks
      revealed that the average flow was only 65 m3/d and the average influent BOD and
      SS were 480 mg/l and 473 mg/l respectively. This corresponded to a high sludge
      loading rate (F:M) of 0.42 d(-1) which accounted for poor performance. Therefore
      the cycle times were extended from 6 h to 7 h and effluent BOD improved from 79
      to 27 mg/l.

PMID- 16104436
TI  - The role of membrane technology in sustainable decentralized wastewater systems.
AB  - Decentralized wastewater treatment has the potential to provide sanitation that
      meets criteria for sustainable urban water management in a manner that is less
      resource intensive and more cost effective than centralized approaches. It can
      facilitate water reuse and nutrient recovery and can potentially reduce the
      ecological risks of wastewater system failure and the community health risk in a
      wastewater reuse scheme. This paper examines the potential role of membrane
      technology in sustainable decentralized sanitation. It is argued that the
      combination of membrane technology within decentralized systems can satisfy many
      of the criteria for sustainable urban water management. In particular, the role
      of membranes as a dependable barrier in the wastewater treatment process can
      increase system reliability as well as lowering the latent risks due to
      wastewater reuse. The modular nature of membranes will allow plant size to range
      from single dwellings, through clusters to suburb size. It is concluded that
      realization of the potential for membrane-based technologies in decentralized
      wastewater treatment will require some progress both technically and
      institutionally. The areas where advances are necessary are outlined.

PMID- 16104437
TI  - Immersed membrane bioreactor (IMBR) for treatment of combined domestic and dairy
      wastewater in an isolated farm.
AB  - In many regions dairy farms and milk processing industries discharge large
      quantities of their wastes to the surroundings posing serious environmental
      risks. This problem is mostly faced in small dairy farms and isolated communities
      lacking both central collection and conventional wastewater treatment systems.
      Dairy wastewater is characterized by high concentrations of organic matter,
      solids, nutrients, as well as fractions of dissolved inorganic pollutants,
      exceeding those levels considered typical for high strength domestic wastewaters.
      With the purpose of treating the combined dairy and domestic wastewater from a
      small dairy farm in the Negev Desert of Israel, the use of a recent emerging
      technology of Immersed Membrane BioReactor (IMBR) was evaluated over the course
      of 500 test hours, under a variety of wastewater feed quality conditions (during
      the test periods, the feed BOD5 ranged from 315 ppm up to 4,170 ppm). The overall
      performance of a pilot-scale Ultrafiltration (UF) IMBR process for a combined
      domestic and dairy wastewater was analyzed based on the Data Envelopment Analysis
      (DEA) method. The IMBR performance in terms of membrane performance (permeate
      flux, transmembrane pressure, and organic removal) and DEA model (Technical
      Efficiency) was acceptable. DEA is an empirically based methodology and the
      research approach has been found to be effective in the depiction and analysis
      for complex systems, where a large number of mutual interacting variables are
      involved.

PMID- 16104438
TI  - Package plant of extended aeration membrane bioreactors: a study on aeration
      intensity and biofouling control.
AB  - Biofouling control is important for effective process of membrane bioreactor
      (MBR). In this study, phenomena of biofouling for immersed type extended aeration
      MBR with two different anti-fouling aeration intensities were studied through a
      laboratory set up. The objectives of this study were (a) to observe biofouling
      phenomena of MBR that operates under different anti-fouling bubbling intensity,
      and simultaneously monitors performance of the MBR in organic carbon and
      nutrients removal; (b) to compare effectiveness of detergent and detergent-enzyme
      cleaning solutions in recovering biofouled membranes that operated in the
      extended aeration MBR. For MBR, which operated under continuous anti-fouling
      aeration, deposition and accumulation of suspended biomass on membrane surface
      were prohibited. However, flux loss was inescapable that biofilm layer was the
      main problem. Membrane cleaning was successfully carried out with detergent
      enzyme mixture solutions and its effectiveness was compared with result from
      cleaning with just detergent solution.

PMID- 16104439
TI  - Intrathecal ropivacaine versus ropivacaine plus fentanyl for out-patient
      arthroscopic knee surgery.
AB  - We evaluated the effects of low-dose intrathecal ropivacaine with or without
      fentanyl for arthroscopic knee surgery. Fifty patients were randomized in equal
      groups to receive an intrathecal solution (3 ml) containing either 10 mg isobaric
      ropivacaine or 8 mg isobaric ropivacaine plus 25 pg fentanyl. Complete motor
      blockade occurred in 22 patients (88%) in both groups. The time taken to reach
      sensory blockade to T10 and total motor blockade was shorter in the ropivacaine
      treated group, but differences were not statistically significant. The duration
      of sensory and motor blockade was shorter in the ropivacaine plus fentanyl
      treated group. The cephalad spread of sensory blockade was higher with
      ropivacaine than with ropivacaine plus fentanyl. We conclude that although 25
      microg fentanyl added to 8 mg ropivacaine provided shorter motor and sensory
      blockade durations than 10 mg ropivacaine alone, small doses of ropivacaine plus
      fentanyl can be used safely for arthroscopic knee surgery.

PMID- 16104440
TI  - Effect of administration of ketorolac and local anaesthetic infiltration for pain
      relief after laparoscopic-assisted vaginal hysterectomy.
AB  - The efficacy of local anaesthetic infiltration and/or non-steroidal anti
      inflammatory drugs for post-operative analgesia following laparoscopic-assisted
      vaginal hysterectomy (LAVH) was investigated in 83 patients, randomized into four
      groups in this double-blind, placebo-controlled study: group BK, local
      infiltration with bupivacaine and pre-incisional intramuscular (IM) ketorolac;
      group NN, saline local infiltration IM; group BN, local infiltration with
      bupivacaine and saline IM; group NK, local infiltration with saline and ketorolac
      IM. Post-operative pain scores were assessed at 1 h, 3 h, 6 h, 12 h and 24 h
      using a visual analogue scale (VAS). The major pain site, first analgesic request
      time and incidence of analgesic requests were also recorded. At 1 h, 3 h and 6 h
      after surgery, group BK patients had significantly lower VAS pain scores than
      group NN patients. The first analgesic request time was significantly longer in
      group BK than in groups NN, BN and NK. Pre-incisional treatment with ketorolac IM
      and local infiltration with bupivacaine reduced post-operative pain after LAVH.

PMID- 16104441
TI  - Hydroxyethyl starch inhibits intestinal production of cytokines and activation of
      transcription factors in endotoxaemic rats.
AB  - We studied the effect of hydroxyethyl starch (HES) on intestinal production of
      cytokines and activation of transcription factors in sepsis. Septic rats, induced
      by intraperitoneal lipopolysaccharide (LPS) (5 mg/kg), were treated with
      intravenous HES (16 ml/kg) or saline (64 ml/kg). Rat ileal tissues were collected
      at 2 h, 3 h or 6 h after LPS challenge. Levels of tumour necrosis factor alpha
      (TNF-alpha), interleukin (IL) 1beta, IL-6, IL-8 and IL-10, cytokine mRNAs,
      activities of nuclear factor kappa-B (NF-KB) and activator protein-1 (AP-1), and
      the number of ileal myeloperoxidase (MPO)-positive cells were determined for each
      group. HES significantly reduced the LPS-induced increase in intestinal levels of
      TNF-alpha, IL-1beta, IL-6, IL-8 and their corresponding mRNAs. HES also decreased
      the number of MPO-positive cells induced by LPS and inhibited activation of NF
      kappaB and AP-1. The results suggest that in sepsis, HES may down-regulate
      intestinal pro-inflammatory cytokine production via suppression of NF-kappaB and
      AP-1 activation.

PMID- 16104442
TI  - Predictive value of C-reactive protein in patients with unstable angina pectoris
      undergoing coronary artery stent implantation.
AB  - In-stent restenosis is a major problem following coronary stent implantation, and
      inflammation plays an active role. We evaluated the effectiveness of the
      inflammatory marker C-reactive protein (CRP) as a predictor of in-stent
      restenosis after successful stent implantation, in 86 patients with unstable
      angina pectoris. Plasma CRP was measured in all patients before the procedure,
      and at 48 - 72 h and 1, 2 and 3 months post-procedure. An angiographic loss of
      50% at follow-up was accepted as in-stent restenosis. We found negative and
      positive predictive values of the pre-procedural plasma CRP for determining 6
      month in-stent restenosis of 34% and 61%, respectively. We also found a strong
      correlation between the 3-month post-procedural CRP value and 6-month in-stent
      restenosis; the negative and positive predictive values being 8% and 76%,
      respectively. In conclusion, we showed that a plasma CRP value > 3 mg/l in the
      third month after coronary stent implantation was a strong predictor of
      angiographic in-stent restenosis.

PMID- 16104443
TI  - Effects of levosimendan on left ventricular functional remodelling and exercise
      intolerance: a tissue Doppler study.
AB  - Levosimendan is a calcium sensitizer that demonstrates enhanced myocardial
      contractility. There is little information concerning the effect of levosimendan
      on left ventricular tissue parameters and exercise capacity. We evaluated the
      effects of a 24-h course of levosimendan therapy on cardiac tissue parameters in
      30 patients, aged 48 - 70 years, admitted to our hospital for the management of
      decompensated heart failure. All patients underwent echocardiographic examination
      using tissue Doppler imaging (TDI) and a 6-min walk test. Systolic myocardial
      velocity of the mitral annulus (Sm) was significantly increased in levosimendan
      treated patients compared with placebo-treated patients. There was a positive
      correlation between Sm and exercise capacity. Levosimendan might be expected to
      increase cardiac contractile force, especially Sm velocity, in parallel with
      exercise tolerance. The study has also shown that the progress of ventricular
      function after levosimendan treatment in patients with exercise intolerance could
      be monitored effectively by Sm velocity measurements using TDI.

PMID- 16104445
TI  - Tissue Doppler echocardiography and myocardial performance index in patients with
      scleroderma.
AB  - In this study, left and right ventricular functions were examined
      echocardiographically in 22 patients with scleroderma and 22 healthy volunteers.
      Conventional and tissue Doppler echocardiography and myocardial performance
      indexes were used as measures of right and left ventricular global functions.
      Mitral early diastolic E wave deceleration time, isovolumetric contraction time
      and left ventricular myocardial performance index and peak tricuspid A wave
      velocity were significantly higher in the scleroderma group compared with the
      control group. Mitral and tricuspid E/A ratios were significantly lower in
      patients with scleroderma. In addition, mitral annular and tricuspid annular
      isovolumetric relaxation times and the tricuspid E/E' ratio were significantly
      increased in scleroderma patients compared with the control group. In conclusion,
      in scleroderma patients the global left ventricular functions were depressed and
      diastolic function abnormalities were seen in both right and left ventricles. In
      addition, longitudinal muscle functions of the ventricles were depressed in
      scleroderma patients, as shown by tissue Doppler imaging parameters.

PMID- 16104444
TI  - Safety and immunogenicity of conventional subunit and MF59-adjuvanted influenza
      vaccines in human immunodeficiency virus-1-seropositive patients.
AB  - In this study of influenza vaccination, 37 human immunodeficiency virus (HIV)-1
      seropositive patients were randomized to receive either a vaccine with a
      conventional subunit or one adjuvanted with MF59. Blood samples were collected at
      the time of vaccination, and then 30 and 180 days later, to evaluate
      immunogenicity, CD4+ T-lymphocyte count and HIV-1 RNA levels. Seroconversion
      rates against the three viral strains included in the vaccine ranged between 44%
      and 72% and 53% and 68% for the adjuvanted vaccine and the subunit vaccine,
      respectively. Other criteria of the European Medicines Evaluation Agency were
      also met. Vaccination was not associated with serious adverse events. Local and
      systemic effects were mild and of short duration. CD4+ T-lymphocyte counts and
      viraemia levels were not negatively affected by vaccination. These results
      confirmed the safety and immunogenicity of these currently available vaccines in
      HIV-1-seropositive patients, thus supporting the recommendation for influenza
      immunization in this high-risk category.

PMID- 16104446
TI  - Comparing risk-adjusted hospital mortality for CABG and AMI patients.
AB  - The objectives of this study were to compare the risk-adjusted mortality of
      coronary artery bypass graft (CABG) and acute myocardial infarction (AMI)
      patients simultaneously in six hospitals in Seoul, Korea, and to investigate the
      relationship between these performance measures by developing a predictive model
      of mortality. The medical records of 749 AMI and 564 CABG patients were reviewed.
      A predictive model was developed using logistic regression, including 170
      variables selected as risk factors for risk adjustment. The validity of our
      predictive model was demonstrated to be within an acceptable range. The results
      showed that one hospital with a significantly low AMI mortality rate also had a
      low CABG mortality rate, while another hospital with a significantly high AMI
      mortality rate also had a high CABG mortality rate. Our results implied that
      hospitals providing good-quality medical management of coronary artery disease
      also provided a good-quality surgical service.

PMID- 16104447
TI  - The necessity of chest physical therapy for thoracoscopic oesophagectomy.
AB  - Radical surgery for thoracic oesophageal cancer is highly invasive and often
      leads to respiratory complications; thoracoscopic surgery is a less-invasive
      alternative. We examined the need for chest physical therapy (CPT) after
      thoracoscopic oesophagectomy. Thirty-six consecutive patients, randomly selected
      for either thoracotomy or thoracoscopic surgery, were included in a randomized
      clinical trial and received CPT under the same protocol. During short-term post
      operative follow-up, both groups showed a marked reduction in respiratory
      function and responded to CPT to the same extent, although 2 weeks after surgery
      some parameters of respiratory function were significantly higher in the
      thoracoscopy group. Thoracoscopic surgery has been reported to be less invasive
      than standard thoracotomy, but our results suggest that the procedure is also
      invasive with respect to respiratory function and that CPT should be performed
      before and after thoracoscopic surgery.

PMID- 16104448
TI  - Assessment of peripheral neuropathy using measurement of the current perception
      threshold with the neurometer in patients with type 2 diabetes mellitus.
AB  - Measurement of current perception threshold (CPT) using the Neurometer at 2000,
      250 and 5 Hz assesses function in three different nerve fibre types. This method
      was used to investigate peripheral neuropathy in 116 patients with type 2
      diabetes mellitus and 38 healthy controls. The CPT at 2000 Hz was significantly
      higher in diabetic patients than in controls, and showed a significant negative
      correlation with motor and sensory nerve conduction velocities. At 250 Hz, CPT
      showed a significant positive correlation with the vibration perception
      threshold. At 5 Hz, the change in systolic blood pressure in the Schellong test
      in patients with hypoaesthesia tended to be less than in those with normal
      sensation or hyperaesthesia. Significantly higher CPT values were obtained in
      patients with proliferative diabetic retinopathy and macroalbuminuria. These data
      suggest that CPT is useful in detecting abnormalities of myelinated as opposed to
      unmyelinated nerve fibres in patients with type 2 diabetes.

PMID- 16104449
TI  - Brain natriuretic peptide and the severity of aortic regurgitation: is there any
      correlation?
AB  - We aimed to evaluate the correlation between aortic regurgitation severity and
      brain natriuretic (BNP) levels as a marker for left ventricular dysfunction.
      Sixty consecutive male patients (mean age 22 +/- 3 years) with isolated chronic
      aortic regurgitation were enrolled in the study together with a control group of
      30 age-matched healthy volunteers (group A). Patients were classified with regard
      to aortic regurgitation vena contracta width as follows: group B, < 3 mm, mild (n
      = 16); group C, > or = 3 and < 6 mm, moderate (n = 26); group D, > or = 6 mm,
      severe (n = 18). BNP measurements were performed with a fluorescence immunoassay
      kit. BNP levels were increased in patients with aortic regurgitation, and
      severity of regurgitation had a significant influence on BNP levels. This effect
      can be explained by the volume loading effect of aortic regurgitation.

PMID- 16104450
TI  - Pure red cell aplasia and myelofibrosis in B-cell neoplasm.
AB  - We describe an unusual case of B-cell neoplasm accompanied by pure red cell
      aplasia (PRCA) and myelofibrosis in a 67-year-old male presenting with severe
      anaemia. A few unclassified, myeloperoxidase-negative blastoid cells were seen on
      bone marrow aspiration, and erythroid cell hypoplasia and myelofibrosis on bone
      marrow biopsy. An autoimmune PRCA was suspected, as serum CH50, C3 and C4 levels
      were consistently low. Ciclosporin was effective in treating the anaemia, but
      anaemia returned when the drug was discontinued. Thirteen months later, the
      patient was admitted with pleural effusion and ascites that contained monoclonal
      CD19+ CD20+ immature blast cells with a complex karyotype, thought to be
      neoplastic B-cells. The unclassified blastoid cells seen earlier may therefore
      have been from the same origin. The patient deteriorated rapidly and died. Only
      one case of non-Hodgkin's lymphoma with PRCA and myelofibrosis has been reported
      previously. We discuss the possibility that dysregulated T-cells induced by
      neoplastic B-cells may have given rise to concomitant PRCA and myelofibrosis.

PMID- 16104451
TI  - Surgical treatment of pulmonary arteriovenous malformation: report of two cases
      and review of the literature.
AB  - Pulmonary arteriovenous malformations (PAVMs) are rare anomalies. The degree of
      right-to-left shunting, which can lead to cyanosis and paradoxical embolism
      causing neurological complications, determines the prognosis. We report two cases
      of PAVM and review the literature. A 45-year-old woman with clinical signs and
      symptoms of PAVM was examined using several different scanning techniques, which
      showed a large PAVM in the lower lobe of her right lung. A lobectomy was
      performed, which revealed a 5 cm diameter PAVM with one feeding artery and
      multiple veins. Intravenous angiography of a 7-year-old girl with symptoms of
      fatigue and acro-cyanosis confirmed the presence of a large PAVM in her right
      lower lobe. The PAVM had two major arteries arising from the aorta, which were
      ligated during a lobectomy. Both patients recovered well following surgery.
      Although PAVMs are rare, their neurological and haemodynamic consequences may be
      fatal. Interventional treatment techniques, including surgery, are usually
      curative.

PMID- 16104452
TI  - America's hospitals: cornerstones of community care.

PMID- 16104453
TI  - Patient involvement: a vital principle for patient-centred health care.
AB  - Chronic conditions account for over half of the global disease burden (WHO, 2004)
      and is predicted to continue to rise. This is placing an ever-increasing burden
      on health systems, originally designed to address acute medical conditions. In
      order to cope with the continuing increase in the number of patients with chronic
      conditions, health systems need to develop so that they are able to address the
      ongoing needs of these people. This requires a different approach because chronic
      conditions, such as diabetes, heart disease, asthma and cancer, require
      management on an ongoing basis, often for many years or decades. Health systems
      therefore require the personal involvement and commitment of the patient to
      adhere to their treatment and make behavioural changes if they are to effectively
      manage their health care. There is growing evidence that designing health systems
      with the patient at the centre--patient-centred health care--is an appropriate
      way to address the needs of people with chronic conditions. The benefits are that
      it promotes greater patient responsibility and optimal usage which ultimately
      leads to improved health outcomes, quality of life and patient satisfaction (see
      Box 1). Patient-centred health care, achieved through patient involvement in
      health policy, will help ensure that the health system is designed to address the
      needs of patients making it possible for them to be meaningfully engaged in their
      personal care and effectively manage their condition.

PMID- 16104454
TI  - Patient sociality in hospital architectural space: a qualitative case study in
      Namibia.
AB  - The article presents research on the relationship between admitted patients'
      social needs and hospital architectural space in an African context. Interaction
      with relatives and fellow patients is very valuable to the well-being of the
      patient. The results show inflexible and restrictive spatial conditions that
      disturb this interaction, for instance, by aggravating the ubiquitous
      overcrowding and people leaving the ward. One important reason for leaving the
      ward is to socialise with other people. Relatives, who assist with caring tasks
      in the ward, stay overnight in a yard in the hospital grounds under uncomfortable
      and health threatening conditions. The results illustrate how patients' well
      being can improve by removing inflexibility and restrictions on space.

PMID- 16104455
TI  - Hospital disaster medical response: aligning everyday requirements with emergency
      casualty care.
AB  - In this essay, we would like to pragmatically and realistically introduce three
      topics: (a) Within the hospital, critical care is acknowledged as an enormous
      cost driver that becomes even less manageable during a disaster response
      scenario. It is widely recognised that hospital critical care capabilities for
      large scale disaster response require significant increases, but an overarching
      plan to accomplish this goal is lacking. This plan necessarily includes
      equipment, personnel, training, and space expansion. Lesser degrees of illness
      and injury will likely be cared for in other venues. What is required to provide
      'large scale' critical care? (b) During a true large scale disaster with a large
      casualty stream, the mandate is not to provide 'standard of care,' but rather
      'sufficiency of care.' What is that, what does that mean to critical care and the
      hospital, and how is that determined? (c) Are there other mandated in-hospital
      requirements that can be appropriately and successfully leveraged for disaster
      medical response?

PMID- 16104456
TI  - The economics of hospital reform from hierarchical to market-based incentives.
AB  - Heavy investment over the past 30 years has made the hospital sector the largest
      expenditure category of the health system in most developed and developing
      countries. In most countries hospitals remain a critical link to health care,
      providing both advanced and basic care for the population. Often, they are the
      provider 'of last resort' for the poor and critically ill. This article provides
      insights into recent hospital reforms undertaken throughout the world, with an
      emphasis on organisational changes such as increased management autonomy,
      corporatisation, and privatisation. It provides some insights about these popular
      reform modalities from a review of the literature, reform experiences in other
      sectors and empirical evidence from hospital sector itself. The material
      presented tries to answer three questions: (a) what problems did this type of
      reform try to address; (b) what are the core elements of their design,
      implementation and evaluation; and, (c) is there any evidence that this type of
      reform is successful in addressing problems for which they were intended? While
      this paper focuses on issues related to the design of the reforms, the paper also
      reports the findings from a larger study that examined the implementation and
      evaluation of such reforms so that they will be available to countries that are
      considering venturing down this reform path.

PMID- 16104457
TI  - Elective full-body screening examinations: a plea for MRI.
AB  - The use of imaging is generally focussed on detecting and characterising
      suspected or known disease in symptomatic patients. Experience with preventative
      imaging, aiming at the detection of disease prior to its symptomatic
      manifestation, is limited. Screening involves the evaluation of asymptomatic
      individuals at risk for the presence of a particular disease. A screening test is
      designed to detect a targeted disease at a stage which still permits treatment to
      succeed in avoiding morbidity and/or mortality. Diseases worthy of screening
      should be associated with high morbidity and/or mortality if proper treatment is
      not applied sufficiently early. The screening test itself must not cause harm to
      the examined subjects. For the test to be cost-effective, the target disease
      should be highly prevalent in the screened population. Restricting screening to a
      population known to be at increased risk for the target disease enhances the
      test's effectiveness.

PMID- 16104458
TI  - eHealth in Europe: towards higher goals.
AB  - Significant events are unfolding in the field of eHealth in Europe. eHealth has
      been a strategic priority of the European Commission in both the eEurope 2002 and
      2005 Action Plans. But how are developments on the national level progressing?
      The authors contrast the status-quo of eHealth in the EU-15 with the latest
      trends and key action priorities in the EU-25 after the Union's latest
      enlargement in May 2004. The initiatives and actions of the European Commission
      are presented vis-a-vis those of national Member States, particularly in terms of
      strategic priorities and implementation actions. The review is accompanied by an
      analysis of expert feedback on eHealth drivers and barriers.

PMID- 16104459
TI  - Integrating quality, patient safety and risk management.

PMID- 16104460
TI  - [Inductive coupled plasma spectroscopy study of trace elements in gallstones from
      different regions of Oaxaca State].

PMID- 16104461
TI  - Clinical profile of dengue hemorrhagic fever cases in Mexico.
AB  - OBJECTIVE: Dengue hemorrhagic fever is a public health problem in Mexico since
      1994. With four serotypes circulating the risk of epidemic dengue hemorrhagic
      fever is increasing. MATERIAL AND METHODS: We describe the clinical features of
      confirmed cases in the social security health system (IMSS) from 1995 to 2003.
      Clinical picture and epidemiological features were compared and a multivariate
      model was fitted to evaluate associations. RESULTS: Cases were divided into two
      groups: 438 patients with dengue fever, including 109 cases with hemorrhagic
      manifestations without thrombocytopenia, and 977 cases with dengue hemorrhagic
      fever, including 79 deaths. The main risk factors associated with mortality were
      hematemesis (RR 2.6; CI 95% 1.4-4.6) and melena (RR 2.2; Cl 95% 1.2-3.7).
      CONCLUSIONS: Our results characterize the clinical profile of dengue hemorrhagic
      fever cases in Mexico and identify prognostic factors to alert clinician for the
      prevention of a fatal evolution.

PMID- 16104463
TI  - [Profile of sexual behavior in 12- to 19-year-old Mexican adolescents. Results of
      ENSA 2000].
AB  - OBJECTIVE: To describe traits associated with sexual behaviors in Mexican
      adolescents, their knowledge about contraception, and factors associated with
      pregnancy and utilization of contraceptives during first sexual intercourse.
      MATERIAL AND METHODS: Data from the Mexican National Health Survey 2000 (ENSA
      2000) were analyzed. This study, conducted between September 1999 and March 2000,
      was a complex survey with a probabilistic, stratified, and cluster sampling
      design. The sample population included 15 241 adolescents 12 to 19 years of age.
      Data analysis included descriptive statistics and a chi-squared test for
      differences of proportions; also, logistic regression was used to obtain odds
      ratios. RESULTS: A total of 69.2% adolescents reported knowledge of at least one
      contraception method; 16.4% of subjects reported having had sexual intercourse.
      Males initiated sexual intercourse earlier than females and only 37% of all
      adolescents utilized contraceptives during their first sexual intercourse.
      Logistic regression analysis showed that being male, having a higher education,
      having knowledge of at least one contraception method, and having initiated
      sexual intercourse at an older age, were factors associated with utilization of a
      contraception method in their first sexual intercourse. A total of 55.7% of
      sexually active female adolescents had been pregnant. Pregnancy among adolescents
      was associated with low educational level, sexual activity at early age, and to
      have sometime lived in free union. CONCLUSIONS: The majority of sexually active
      adolescents did not use contraception during their first sexual intercourse,
      rendering them at risk of unwanted pregnancies.

PMID- 16104462
TI  - [Epidemiology of Chagas disease in the state of Veracruz].
AB  - OBJECTIVE: To assess the seroprevalence, household risk factors, and
      entomological indicators, in order to frame control measures in 11 Sanitary
      Jurisdictions of the state. MATERIAL AND METHODS: This study included 281 towns,
      2 526 households, and 9782 individuals. Data were collected using a
      questionnaire. Blood was obtained in filter paper and a search for triatomines
      was conducted inside of and around dwellings. Prevalence rates were used to
      quantify exposure to risk factors and seropositivity. Odds ratios with 95%
      confidence intervals and Mantel-Haenszel chi-squared tests were obtained.
      Multivariate analysis was performed with unconditional logistic
      regression,variables included in the model were those that had a p-value up to
      0.20 in the bivariate analysis. The etiologic fraction in the exposed was also
      obtained. RESULTS: The prevalence of Chagas disease was between 0 and 2.8%.
      Jurisdictions at a higher risk wereTuxpan, Panuco and Cordoba; Orizaba showed no
      risk. The main household risk factors were palma/zacate (palm-tree, grass leaves)
      roof and walls, dirt floor, the presence of the vector, and ventilation.
      CONCLUSIONS: Epidemiological surveillance should emphasize health education,
      housing improvement, and use of insecticides.

PMID- 16104464
TI  - [Surveillance of antibiotic utilization and bacterial resistance profiles in
      tertiary level hospitals in Mexico City].
AB  - OBJECTIVE: To identify the levels of antibiotic utilization and the resistance
      profiles of nosocomial bacteria, as well as the strategies to diminish resistance
      to antibiotics. MATERIALS AND METHODS: A descriptive, retrospective (1994-1995)
      study was conducted in six tertiary level hospitals in Mexico City. RESULTS: A
      total of 86% antibiotic resistance was observed in these hospitals. The overall
      consumption of antibiotics per hospital ranged between 44 and 195 Defined Daily
      Doses/100 day-beds. CONCLUSIONS: We identified the components to frame an
      integral surveillance system aimed at improving the use of antibiotics and the
      quality of the bacterial resistance assessment in these hospitals.

PMID- 16104466
TI  - [Influenza vaccination in the elderly population in Mexico: economic
      considerations].
AB  - OBJECTIVE: To estimate costs and health outcomes that could be attained by an
      influenza vaccination program in adults 65 years of age and older in Mexico.
      MATERIAL AND METHODS: Between June and October 2004, a model was constructed to
      estimate the number of life years lost due to influenza and the fraction that
      could be prevented by vaccination among adults 65 years of age and older. The
      model also allowed the estimation of the net cost of a vaccination program,
      including both the cost of delivering the vaccine and savings from prevented
      infections and their treatment costs. RESULTS: Using two scenarios of vaccine
      effectiveness, between 7 454 and 11 169 life years could saved by the vaccine if
      given to all adults 65 years and older in Mexico, with a net cost per life year
      saved between 13 301 and 21 037 Mexican pesos (about dollar 1 210 and dollar 1
      910 US dollars). DISCUSSION: Influenza vaccination among the elderly in Mexico
      would result in savings per life year saved well below the Mexican gross domestic
      product (GDP) per capita, suggesting, even without examining alternative uses for
      these resources, that this is a cost effective intervention in Mexico and
      probably also in other middle-income developing countries.

PMID- 16104465
TI  - [Antibodies against Chlamydophila in patients with acute myocardial infarction
      and coronary risk and their association with mortality].
AB  - OBJECTIVE: The primary aim of this study was to determine whether antibodies
      against Chlamydophila pneumoniae in patients with acute myocardial infarction
      (AMI) and coronary risk factors are associated with death. MATERIAL AND METHODS:
      A cross-sectional study was conducted among 100 patients hospitalized in the
      Coronary Unit of Centro Medico La Raza Hospital of the Mexican Institute of
      Social Security, between 1999 and 2000. Subjects were males and females older
      than 18 years, diagnosed with AMI and coronary risk. Antibodies against
      Chlamydophila pneumoniae, Chlamydophila psitacii and Chlamydia trachomatis were
      measured using an indirect microinmunofluorescence assay. In addition, blood
      samples from 33 patients from the original group were taken when the patients
      were discharged from the hospital,and 3 months after their myocardial infarction.
      Data analysis consisted of geometric means and standard deviations as well as
      odds ratios with 95% confidence intervals. RESULTS: Seventy percent of patients
      presented antibodies against Chlamydophila pneumoniae. Antibodies against
      Chlamydophila psittaci and Chlamydia trachomatis were not identified. No
      statistically significant association was found between antibodies and death in
      these patients with coronary risk factors and AMI. In the subgroup of 33
      individuals 25 had antibodies against Chlamydophila pneumoniae and in 83% of them
      antibodies decreased three months after the AMI event. CONCLUSIONS: Even though
      patients with coronary risk factors and AMI had an increased seropositivity for
      Chlamydophila pneumoniae it was not significantly associated with death.

PMID- 16104467
TI  - [Occupational leptospirosis in a Colombian Caribbean area].
AB  - OBJECTIVE: To establish the seroprevalence of infection by Leptospira in an
      occupational setting in Cordoba. MATERIAL AND METHODS: A cross-sectional study
      was conducted among 334 farmworkers, butchers, and garbage collectors, to
      identify the presence of anti-leptospira IgM antibodies, in the Department of
      Cordoba, Colombia. Stratified sampling proportional to the number of inhabitants
      and occupation was used to select the sample population (confidence level 99.9%,
      error 0.5%, prevalence 72%). The SPSS software 11.0 version was used to perform
      non parametric tests with p < 0.05, as well as odds ratios with confidence
      intervals. RESULTS: The prevalence of previous infection by Leptospira was high
      (13.1%). No differences among areas were found, however, higher infection was
      associated with living in Cienaga de Oro municipality (OR = 3.52 Cl 1.70-7.26) (p
      = 0,00283). Being a farmer was also a risk factor for infection (OR = 2.04 Cl
      1.080-3.85) (p = 0.025), as well as drinking water from a dam (OR = 2.4 CI 1.24
      4.70) (p = 0.00787). CONCLUSIONS: The rate of infection is important and a
      significant public health problem in this area of the Colombian Caribbean coast.

PMID- 16104468
TI  - [Medical ethics, health and social protection. Miguel E. Bustamante Magisterial
      Lecture].

PMID- 16104469
TI  - The role of the healthcare assistant in tissue viability.

PMID- 16104470
TI  - Tissue viability in rheumatoid arthritis.

PMID- 16104471
TI  - EPUAP statement on prevalence and incidence monitoring of pressure ulcer
      occurrence.

PMID- 16104472
TI  - [Preventing obesity, acting and acting quickly].

PMID- 16104473
TI  - [Evolution of the development of generic drugs].

PMID- 16104474
TI  - [Rickets].

PMID- 16104475
TI  - [Crohn disease, hemorrhagic rectal colitis, investigation on the care of
      patients].

PMID- 16104476
TI  - [Realities of hemophilia].

PMID- 16104477
TI  - [Hemophilia. Education of children and parents, a fundamental measure].

PMID- 16104478
TI  - [Emergencies in adolescents: how can one recognize those who are in danger?].

PMID- 16104479
TI  - [The houses of the Institute for the Prevention of Domestic Accidents (IPAD), at
      the heart of domestic prevention].

PMID- 16104480
TI  - [Infliximab in Crohn disease].

PMID- 16104481
TI  - [Prevention of medication errors and nosocomial infections by the regional
      Commissions of Reconciliation and Prevention: outline of the stage of
      scheduling].

PMID- 16104482
TI  - [Health in Senegal: doctors and soldiers].

PMID- 16104483
TI  - Diabetes and esophageal motility disorders--need for clinical relevance.

PMID- 16104484
TI  - Esophageal motility disorders in diabetics.
AB  - OBJECTIVE: To see the presence of esophageal motor disorders in diabetic patients
      and compare it with controls at the Department of Medicine Ziauddin Medical
      University Hospital, Karachi. METHODS: Diabetic patients admitted at Ziauddin
      Medical University Hospital, Karachi were taken as study subjects, whereas age
      and sex matched healthy volunteers not suffering from any disease neither taking
      any medication for dyspepsia were taken as controls Esophageal manometry was done
      to see the motility disorders in diabetic patients and controls. RESULTS: Resting
      pressure of the lower esophageal sphincter in diabetics was similar to controls.
      Percentage of relaxation of the lower esophageal sphincter was low in diabetics.
      Amplitude of esophageal peristalsis and duration of contraction was similar in
      both the groups. Propulsive velocity of peristalsis was slower in diabetics.
      Parameters of upper esophageal sphincter were similar in diabetics and controls.
      Abnormal peristaltic waves like aperistalsis of the esophageal body, high
      amplitude and broader waves, absent contraction and hypertensive lower esophageal
      sphincter were seen in diabetics only. CONCLUSIONS: Poor relaxation of the lower
      esophageal sphincter and slow propulsive velocity were noted in diabetics.
      Abnormal peristaltic waves like aperistalsis of the esophageal body, high
      amplitude and broader waves, absent contraction and hypertensive lower esophageal
      sphincter were seen in diabetics only.

PMID- 16104485
TI  - Surgical palliation for unresectable pancreatic carcinoma.
AB  - OBJECTIVES: To review the results of surgical palliation for unresectable
      pancreatic carcinoma, and to analyze the morbidity and mortality associated with
      the surgical procedure. The reasons for readmission after discharge from the
      hospital were also analyzed. METHODS: A retrospective study from 1995 to 2001 was
      done on 30 patients with pancreatic cancer operated with palliative intent, or
      those explored with curative intent but histopathology revealed positive
      resection margins or lymph node metastasis. RESULTS: Twenty-five (83.25%)
      patients were above 50 years of age. There were 16 (53.28%) male, and 14 (46.62%)
      females, 8 (26.64%) had diabetes mellitus, 2 (6.66%) chronic pancreatitis and 4
      (13.32%) had smoking as risk factors. Twenty-three (76.59%) patients presented
      with jaundice, 18 (59.94%) with weight loss, 17 (56.61%) with epigastric pain, 15
      (49.95%) with anorexia and 14 (46.62%) with vomiting. Whipple's procedure was
      performed in 9 (29.97%) patients, triple bypass in 13 (43.29%),
      choledochojejunostomy and gastrojejunostomy in 3 (9.99%) and gastrojejunostomy
      alone in 5 (16.65%) patients. Seven (23.31%) patients had preoperative
      ultrasonography, while CT Scan was done in 24 (79.92%) and ERCP in 8 (26.64%)
      patients. Histopathology showed positive resection margins in 9 (29.97%) patients
      and lymph node metastasis in 5 (16.65%) patients. Seventeen (56.61%) patients
      received less than 2 units of pack cells transfusion. Most of the patients
      remained admitted in the hospital between 20 to 30 days. Post-operatively,
      delayed gastric emptying was detected in 6 (19.98%) patients, cholangitis in 2
      (6.66%), wound infection in 3 (9.99%), anastomotic leak in 2 (6.66%) and line
      sepsis in 2 (6.66%) patients. Three (9.99%) patients expired in hospital post
      operatively. The reasons for re-admission after discharge included abdominal pain
      in 9 (29.97%) patients, anemia in 3 (9.99%), intestinal obstruction in 3 (9.99%)
      and urinary tract infection in 2 (6.66%) patients. Follow up record was available
      for 22 (73.26%) patients. Six (19.98%) patients survived for 5 to 6 months and 9
      (29.97%) had a survival between 7 to 10 months. CONCLUSION: A single surgical
      procedure can palliate all three symptoms associated with unresectable pancreatic
      carcinoma, and can be carried out with reasonable safety in selected patients.
      The commonest indication for re-admission is severe abdominal pain associated
      with advanced malignancy, hence chemical splanchiectomy may also be considered at
      the time of surgical exploration.

PMID- 16104486
TI  - Myelography in spinal disorders--experience of 1400 cases.
AB  - OBJECTIVE: To evaluate the diagnostic importance of myelography in spinal
      disorders, in correlation with clinical presentation of the patients. METHODS:
      Patients selected for myelography had presented with history of various spinal
      disorders such as low backache, neurogenic claudication, paraparesis or
      paraplegia, quadriparesis or quadriplegia, trauma to spinal region and infective
      spondylitis. Patients excluded were those with history of allergies to iodinated
      contrast agents, seizures coagulopathy and pregnant women. Contrast agent was
      water soluble non ionic agent--lohexol. Spinal Needles used were of 20,22 and 25
      gauge. X-Ray machine with tiltable table was used for myelography. RESULTS: There
      were 1400 patients of whom 935 were males and 465 females with male to female
      ratio of 2.1. Age range was 8 to 65 years. Spinal disorders diagnosed on
      myelography were lumbar disc prolapse 866 (60%) cases, lumbar canal stenosis 113
      (8%), thoracic disc protrusions 15 (1%), infective spondylitis 53 (4%) cases,
      spinal tumors 36 (2.5%), spinal dysraphism 28 (2%) and traumatic spine in 85 (6%)
      cases. Free flow of contrast agent with no block was found in 149 (10.64%) cases.
      These were subjected for MRI scan which revealed significant pathological lesion
      of surgical importance in 23 cases (1.64%) only. CONCLUSION: Myelography is the
      least expensive valuable diagnostic test in spinal disorders specially in lumbar
      disc prolapses and lumbar canal stenosis.

PMID- 16104487
TI  - Improving vaccination status of children under five through health education.
AB  - OBJECTIVE: To improve awareness and knowledge of mothers regarding vaccine
      preventable diseases and the immunization status of children under five through
      health education messages by medical students, at Gulshane-Sikanderabad, a
      squatter settlement adjacent to Ziauddin Medical University, Karachi. METHODS:
      The undergraduate medical students' visit families in the squatter settlement.
      This study compared the effect of intervention by medical students on vaccination
      status of children under five in the intervention households versus those without
      intervention. A baseline study was done in 1998 and a follow-up study was done
      after four years to assess the differences in knowledge and practices of mothers
      regarding immunization. RESULTS: A total of 110 houses from block I and 207
      houses from block V were selected. An increase of 22% (52% vs 30%) in block-I (p
      = 0.003) and 19% (32% vs 13%) increase in block V was seen in the utilization of
      PHC Center for vaccination (p = 0.001). Mothers' knowledge regarding the age when
      first vaccine is administered to the child, increased in the follow-up from 60%
      to 76.5% (p < 0.01) in block I and from 50% to 62% in block V. The immunization
      status increased significantly in block I from 46.5% to 75% after the
      intervention (p < 0.005), no significant difference could be seen in block V (p =
      0.16). In the follow-up survey a significant difference was seen in the
      vaccination status between the two blocks (p = 0.001). CONCLUSION: The health
      education messages significantly increased the vaccination status of children
      under 5 in the intervention area.

PMID- 16104488
TI  - Clinical study on the use of nozovent in a tertiary care setting.
AB  - OBJECTIVE: To assess the effectiveness of the Nozovent device in Pakistani
      subjects at Aga Khan University Hospital, Karachi and Sir Ganga Ram Hospital,
      Lahore from 15 January 2001 to 15 January 2002. METHODS: Sixty males and 40
      females were selected by non probability purposive sampling, from OPD of ENT
      Department, complaining of nasal obstruction due to various reasons, e.g.
      vasomotor rhinitis, allergic rhinitis, congestion during pregnancy and
      menstruation, common cold, traumatic nose and nasal valve problem. RESULTS: All
      patients benefited subjectively but the degree of relief varied in individuals.
      CONCLUSION: The Nozovent provides a unique method to relieve nasal obstruction
      with no side effects.

PMID- 16104489
TI  - Diagnostic value of fine needle aspiration cytology in parotid tumors.
AB  - OBJECTIVE: To evaluate the usefulness and accuracy of fine needle aspiration
      cytology in the diagnosis of parotid gland tumors. METHODS: We reviewed files of
      all patients who underwent parotidectomy for various parotid pathologies at Aga
      Khan University Hospital. Study design included a comparison between results of
      preoperative FNAC with final histopathological diagnosis. Galen & Ganbino method
      was used to calculate sensitivity and specificity of FNAC. RESULTS: Among 50
      patients reviewed, there was one false positive and 3 false negative results
      reported on FNAC. This gives a sensitivity of FNAC for reporting malignancy to be
      74% and specificity to rule out malignancy 97%. No significant complications were
      reported while performing the procedure. CONCLUSION: FNAC is a safe and effective
      modality in diagnosis and treatment planning of patients with parotid tumors.

PMID- 16104490
TI  - Vaginal discharge: perceptions and health seeking behavior among Nepalese women.
AB  - OBJECTIVES: To understand women's perceptions and health seeking behavior and the
      association between vaginal discharge, clinical signs and laboratory findings as
      a presentation of sexually transmitted diseases (STD). METHODS: We conducted five
      focus group discussions with women attending the outpatient department in a large
      public hospital in Katmandu, Nepal, during May-June 1997. We also interviewed
      seventy women presenting with vaginal discharge to the same hospital, through
      structured questionnaire. Women presenting with discharge were also examined and
      investigated for six common sexually transmitted diseases and reproductive tract
      infections. RESULTS: In the focus groups vaginal discharge was identified as a
      common disease distinct from STDs, for which women can seek treatment. STDs were
      considered as social diseases transmitted to women through multiple sexual
      partners and not from husband. Patients with vaginal discharge preferred
      traditional healers and pharmacist. Clinical signs were inconclusive for type of
      infection. Simple laboratory tests identified etiologic agent in 64 (91%)
      patients and the three commonest infections were Moniliasis (78%), Bacterial
      Vaginosis (25%) and Trichomoniasis (17%). CONCLUSION: Vaginal discharge may be
      used as a risk marker for identification of STDs by Primary Health Workers. Low
      cost investigations should be made available at the secondary care level for
      identification of most common Reproductive Tract Infections. Communication
      campaigns should target the misconceptions that exist in the communities local
      context related to the prevention, treatment and control of vaginal discharge and
      STDs.

PMID- 16104491
TI  - PCNL (percutaneous nephrolithotomy): first year experience.

PMID- 16104492
TI  - Effects of apolipoprotein E polymorphism on the development of stroke.

PMID- 16104493
TI  - Rhinocerebral mucormycosis.

PMID- 16104494
TI  - Case of inhaled prostaglandin E1 used to improve hypoxia in ARDS.

PMID- 16104495
TI  - Funnel neck--deformity of the neck: an unusual sequel after total laryngectomy.

PMID- 16104496
TI  - Left main coronary artery aneurysm associated with severe atherosclerosis: a case
      report from Pakistan.

PMID- 16104497
TI  - Coronary heart disease risk factor profile of children in a country with
      developing economy--an issue that needs prompt attention.

PMID- 16104498
TI  - [Studies on Armillariella mellea cultivation with different kinds of trees].
AB  - The branches of several common trees in north China were selected to cultivate
      Armillariella mellea. The rhizomorph and growth speed of Armillariella mellea
      were measured,and the extracellular laccase activity was determined. The results
      showed that all tested trees except Sophora japonica and Amorpha fruiticosa were
      suitable to the growth of Armillariella mellea.

PMID- 16104499
TI  - [Species and geographic distribution of large-flowered taxa of Epimedium in
      China].
AB  - OBJECTIVE: To introduce species and geographic distribution of large-flowered
      taxa of Epimedium L. in China. METHODS: Resources investigation and taxonomy
      study. RESULTS: There are 27 species large-flowered taxa of Epimedium in China.
      CONCLUSION: 13 species in Sichuan, 9 species in Hubei, 8 species in Guizhou, 4
      species in Hunan, 3 species in Guangxi, 2 species in Chongqing, 2 species in
      Yunnan, 1 species in Jiangxi, 1 species in Shanxi, 1 species in Jilin, 1 species
      in Liaoning and 1 species in Heilongjiang.

PMID- 16104500
TI  - [Investigation on the chromatogram of diterpenoids in Pteris semipinnata by HPLC
      APCI-MS].
AB  - To identify and compare the main peaks of HPLC-APCI-MS FP of the diterpenoids in
      Pteris semipinnata collected from different region and time, a quadrupole mass
      spectrometer coupled with atmospheric pressure chemical ionization interface was
      employed as a detector for HPLC to establish total ion chromatography. HPLC
      retention time and MS spectrum were used to identify comprehensively. 4F, 5F and
      6F were identified from the chromatography comparing with their standards. The
      saturated state of 6F and glycoside of 4F and 5F were inferred. The content of 5F
      in samples collected from region of Guangzhou or in Nov. and Dec. were
      comparatively higher. This method is highly effective and fast,which can be
      applied to research and develop for diterpenoids in Pteris semipinnata L as new
      antitumor drug resource.

PMID- 16104501
TI  - [Identification of categories of Radix Rehmannia by IR spectroscopy and compare
      software].
AB  - OBJECTIVE: To identify the categories of Radix Rehmannia between the wild and the
      planting, different stored time, (gained in 2000,2002) , trueborn place (Henan)
      and no-trueborn places. METHODS: FTIR combined compare software, and the data was
      dealt with the means of normalization in computer. RESULT: The wild and the
      planting have evident difference. They can be identified for the different stored
      time completely. The identification percentage between trueborn place and no
      truedborn places is more than 90%. CONCLUSION: The method is fast, accurate.

PMID- 16104502
TI  - [Studies on chemical constituents from the flowers of Carthamus tinctorius L].
AB  - OBJECTIVE: To investigate the chemical constituents from the flowers of Carthamus
      tinctorius. METHOD: The chemical constituents were isolated and repeatedly
      purified on silica gel column. They were identified and structurally elucidated
      by means of physio-chemical constants and spectral analysis. RESULT: Eight
      compounds were identifed as palmitic acid (I), 1-O-hexadecanolenin (II), trans-3
      tridecene-5,7,9,11-tetrayne-1,2-diol (III), trans-trans-3,11-tridecadiene -5,7,9
      triyne -1,2-diol (IV), coumaric acid (V), daucosterol (VI), apigenin (VIl) and
      kaempferol (VIII), respectively. CONCLUSION: Two compounds (II and III) were
      obtained from the genus of Carthamus for the first time.

PMID- 16104503
TI  - [Studies on the chemical constituents from the leaf of Liquidambar formosana
      Hance].
AB  - OBJECTIVE: To study the chemical constituents from the methanolic extract from
      the leaf of Liquidambar formosana Hance. METHOD: The compounds were separated
      with the column chromatographic and Prep HPLC, and their structures were
      identified by chemical and spectroscopic methods. RESULTS: Three compounds were
      isolated from the methanolic extract. They were identified as: beta-sitosterol
      (I), alpha-amyrin (II) and oleanonic acid (III). CONCLUSION: All of them were
      isolated from this plant for the first time.

PMID- 16104504
TI  - [Experimental study on MCF-7 cell apoptosis induced by ursolic acid].
AB  - OBJECTIVE: To study the effects of ursolic acid (UA), apentacyclic triterpene
      acid, on MCF-7 cell apoptosis. METHODS: MCF-7 cells were cultured with different
      concentrations of UA. Viability of UA-induced MCF-7 cells was evaluated by MTT
      assay. Cell cycle and sub-G1 peak were performed by FCM. Morphologic changes of
      UA-treated cells were observed by light microscope. Apoptotic cells with
      condensed or fragmented nuclei were visualized by Ho33258 and PI staining by a
      fluorescence microscope (EX: U.V., Green light). p 53 protein expression was
      analyzed by fluorescence immunohistochemical method (SABC-Cy3). RESULT: 24 hours
      after UA treatment, inhibition of MCF-7 cell proliferation was concentration
      dependent. The IC50 value for UA was 22.6 +/- 3.0 micromol/L. Cell cycle analysis
      by FCM showed that 50 micromol/L of the drug arrested MCF-7 cell cycle at G0-G1
      phase. Morphological changes of MCF-7 cells exhibited many of the hallmark
      features of apoptosis, including condensation of chromatin and DNA fragmentation.
      UA increased p 53 protein expression. CONCLUSION: The results suggest that UA
      evokes MCF-7 cell apoptosis is correlation with the up-regulation of p 53. The
      study indicated that UA might be a potential Chinese medical component for breast
      neoplasm.

PMID- 16104505
TI  - [Inhibition of proliferation and induction of apoptosis by tanshinone II A in NCI
      H460 cell].
AB  - OBJECTIVE: To investigate the inhibition of tanshinone II A in NCI-H460 cell line
      and its mechanism. METHODS: MTT was used to measure the levels of the
      proliferation of NCI-H460 cultured with tanshinone II A in different
      concentrations. The effects of tanshinone II A on cell cycle of NCI-H460 were
      observed by FCM. After treated with tanshinone II A for 48h, the level of mRNA of
      bcl-2 and C-myc in NCI-H460 was tested by RT-PCR method. RESULT: The
      proliferation of NCI-H460 was obviously inhibited by tanshinone II A in a dose
      dependent manner. The outcome of FCM showed that the apoptotic cell rate was
      1.2%, 3.4%, 7.7% respectively, when cultured with tanshinone II A at 0.5
      microg/ml for 24, 48, 72 h. The apoptotic cell rate was 2.6%, 5.9%, 13.4%, when
      cultured with tanshinone II A at 1.0 microg/ml for 24, 48, 72 h. The apoptotic
      cell rate was 4.1%, 8.7%, 37.6%, when cultured with tanshinone II A at 2.0
      microg/ml for 24, 48, 72 h. The outcome of RT-PCR showed that the expression of
      proto-onco gene bcl-2 and C-myc was notably decrease, after cultured with
      tanshinone II A for 48 h. CONCLUSION: Tanshinone IIA can inhibit the
      proliferation of NCI-H460 and induce the apoptosis of the cell.

PMID- 16104506
TI  - [Study on the effect of theaflavins on the adhesion between monocyte and
      endothelial cells].
AB  - The effect of theaflavins (TFs) on the adhesion between monocyte and endothelial
      cells induced by oxidized low density lipoprotein was studied. The experiments of
      cells-adhesion,the cells ELISA were applied. The results showed that TFs could
      significantly inhibit the adhesion between monocyte and endothelial cells, and
      the expression of cell adhesion molecule (ICAM-1) and vascular cell adhesion
      molecule (VCAM-1). That maybe one of the mechanisms in antiatheroclerosis and
      antiadhesion between monocyte and endothelial cells.

PMID- 16104507
TI  - [Effects of 5F from Pteri semipinnata on the expression of ETS-1 mRNA and VEGF
      protein of highly metastatic ovarian carcinoma HO-8910PM cells].
AB  - OBJECTIVE: To study the effect of 5F from Pteri semipinnata L. on the expression
      of ETS-1 mRNA and VEGF protein, and to investigate the antitumor mechanisms of 5F
      from Pteri semipinnata L. METHODS: RT-PCR assay was used to assess the expression
      level of ETS-1 mRNA. The expression level of VEGF protein was assessed by Western
      blot analysis. RESULTS: The expression level of of VEGF protein obviously
      decreased in HO-8910PM cells treated with 25 to approximately 100 micromol/L 5F
      for 24 hours. 5F significantly down-regulated the expression of ETS-1 mRNA.
      CONCLUSION: The antitumor activity of 5F from Pteri semipinnata L is involved in
      the expression of ETS-1 mRNA and VEGF protein.

PMID- 16104508
TI  - [Effects of benefiting-bone capsule on the expression of transforming growth
      factor-beta1 mRNA in bone tissue of the ovariectomized rats].
AB  - OBJECTIVE: To investigate the effects of Benefiting-bone capsule (BBC) on the
      expression of transforming growth factor-beta1 mRNA in bone tissue of the
      ovariectomized rats to further explain the mechanism of BBC on preventing and
      treating osteopoprosis. METHODS: Twenty-four rats were randomly chosen from 72
      female SD rats aged 10 months, which were classified into group A and B of sham
      operation dealing with normal physiological saline. The left 48 rats were
      randomly divided into 4 groups after ovariectomy: group A and B of osteoporotic
      animal model with normal physiological saline, prevented and treated groups of
      osteoporotic animal model with BBC. Each group included 12 rats. Ovariectomy was
      used to establish the osteoporotic animal model and the expression of TGF-beta1
      mRNA on gene level in bone tissue was detected by real time fluorescence
      quantitative PCR (FQ-PCR) method. RESULTS: The expression of TGF-beta1 mRNA on
      gene level in bone tissue of the groups of osteoporotic animal model with BBC
      were all higher than that of the groups of osteoporotic animal model, which were
      close to the groups of sham operation. CONCLUSION: BBC can improve the expression
      of TGF-beta1 mRNA on gene level in bone tissue, which may be the mechanism of BBC
      on preventing and treating osteoporosis.

PMID- 16104509
TI  - [The effects of kuijiekang capsule on ulcerative colitis induced by TNBS in
      rats].
AB  - OBJECTIVE: To evaluate the effects of Kuijiekang Capsule (KJK) on rats colitis
      induced by TNBS. METHODS: Rats with TNBS/ethanol-induced colitis were used and
      treated with KJK. The experimental animals were divided into 6 groups: control
      group, model group, SASP group (0.50 g/kg), KJK group (0.64, 0.32, 0.16 g/kg).
      The animals were administrated 0. 5% carboxymethyl cellulose, SASP and KJK
      respectively (from the 6th d after the establishment of ulcerative colitis model
      to the end of the experiment, 18 d totally). At the end of the experiment, the
      colon mucosal damage index (CMDI), the activity of myelperoxidase (MPO) and the
      occult blood test (OB) in feces were observed, the mucosa pathohistology was
      measured and thymus and spleen of rats were weighed respectively. Meanwhile, the
      content of malondiadehyde (MDA) , superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px) of colonic tissue were detected. RESULTS: The remarkable
      effects of KJK at dosage of 0.64, 0.32 g/kg on TNBS-induced colitis were
      observed, the extent of CMDI and OB were decreased, MPO activeity of colonic
      tissue was reduced. The extent of atrophy of thymus gland and intumesce of spleen
      of rat were ameliorated. Meanwhile, the content of MDA was reduced, and the
      activities of SOD and GSH-Px were increased. Pathological histology results
      showed that KJK could alleviate the pathohistological lesion of the colon of rat.
      CONCLUSION: Treatment with KJK shows beneficial effects on the mucosal damage of
      rats colitis induced by TNBS/ethanol. The mechanism of the actions of KJK may
      relate to anti-inflammatory effect, immunoloregulation and anti-oxidation.

PMID- 16104510
TI  - [Calcium antagonistic effect of Xanthotoxol on isolated guinea pig atria].
AB  - OBJECTIVE: To study the mechanism of depressant effect of xanthotoxol (XT) on
      contractility in the isolated guinea pig atria. METHODS: The contractile force of
      the isolated left atria was determined by tension recording method. RESULTS: In
      the experiments on contractility of the left atria XT and Verapamil (Ver)
      significantly depressed the positive staircase phenomena, which was reversed by
      Ver but not by XT. However, the post-rest potentiation of myocardial contraction
      in the left atria was only markedly decreased by XT but not by Ver. Furthermore,
      XT not only attenuated the positive inotropic action, but also delayed the
      following toxicity response induced by ouabain in the isolated left atria.
      CONCLUSION: XT blocked not only the voltage dependent calcium channel, but also
      the receptor operated calcium channel in the isolated guinea pig atria.

PMID- 16104511
TI  - [Experimental studies on the extract technology of tea polysaccharide from green
      tea by orthogonal test].
AB  - The effect factor of extraction of tea polysaccharide was investigated with
      orthogonal test. The effects of extraction conditions on yield, purity of tea
      polysaccharide and cost of extraction were discussed. The results show that the
      optimum conditions for extracting tea polysaccharide from green tea are as
      follows: extraction time is 30 minutes with water at 95 degrees C, extraction
      times with chloroform is 3, extraction times with CH3COOC2H5 is 1 and
      concentration of alcohol is 60%.

PMID- 16104512
TI  - Studies on the microwave extraction of the yellow pigment from Rabdosia serra
      (Maxim.) Hara.
AB  - A new method of microwave extraction was used to extract the yellow pigment from
      Rabdosia serra (Maxim.) Hara. The extraction processes were investigated and the
      optimal conditions were determined as follows: raw material is 2. 0000 g dry
      powder, the extraction agent is 95% alcohol, the ratio of raw material to
      extraction agent is 1:60 (g:ml) , microwave power is 464 W, extraction time is
      350 s, extraction times is 3. Under the optimal conditions, extraction rate is
      90.6%, productive rate is 12.7%, colority E (1%, 330 nm) is 53.3 and pH value of
      the extractive is 6.0. Compared with solvent extraction, microwave extraction
      reduces extraction time from 6 h to 350 s and increases extraction rate from
      90.4% to 90.6%.

PMID- 16104513
TI  - [Selection of the receptor fluid based on main drug' s dissolvability in the in
      vitro skin permeation study].
AB  - OBJECTIVE: To select the receptor fluid used in the in-vitro skin permeation
      study of CVD from Shuxin transdermal patch. METHODS: The saturated concentration
      of CVD in different receptor fluid was determined by RP-HPLC with precolumn
      ultraviolet derivatization. And the selection of receptor fluid was based on main
      drug's dissolvability. RESULTS: The concentration of CVD in 30%
      ethanol/physiological saline was the highest among seven kinds of receptor fluid.
      CONCLUSION: The method used to select the receptor fluid based on main drug's
      dissolvability in the in-vitro skin permeation study is credible and convenient.

PMID- 16104514
TI  - [Study on extraction of zhuyun 3# by supercritical CO2].
AB  - To optimize the extraction process for zhuyun 3# pill by supercritical CO2. Five
      kinds of supercritical CO2 extraction method had been applied. The methods were
      estimated by the pharmacological results and the content of flovone. The best
      extraction process for zhuyun 3# pill was that Luzhenzi, Baizhu and Xuduan were
      extracted with supercritical CO2 and the residue was estracted by water, the
      other five kinds of medicinal materials were extracted by water.

PMID- 16104515
TI  - [Cross-population interactions of influenza A viruses in man and animals].
AB  - The paper considers the molecular mechanisms of host specificity of influenza A
      viruses, which are associated with the crossing of host-specificity barriers,
      which may give rise to new pathogenic variants and a subsequent risk of a
      pandemic.

PMID- 16104516
TI  - [Evolution of avian influenza viruses H5N1 (1997-2004) in southern and south
      eastern Asia].
AB  - Highly pathogenic avian influenza viruses of the H5N1 subtype are widespread and
      have become endemic in poultry in southern and southeastern Asia. An
      unprecedented epizootic was caused by these viruses in 8 countries in the winter
      of 2003 to 2004. This fact along with more frequent human cases of the infection
      with unusually high mortality rates in Vietnam and Thailand raises concern that
      these H5N1 events may lead to a new influenza A virus pandemic. This review
      summarizes the results of studies dealing with the ecology and evolution of avian
      influenza H5N1 viruses in southern and southeastern Asia since 1997. The
      pathogenesis of the infection in human beings and laboratory animals and possible
      determinants of the high pathogenicity of H5N1 viruses in mammals are considered.
      A scheme for designing modified H5N1 vaccines using the latest advances in
      reverse genetics of influenza viruses is given.

PMID- 16104517
TI  - [Hepatitis C virus proteins in the liver cells in acute hepatitis C: their
      association with liver damage and with the outcome of the disease].
AB  - The accumulation of individual hepatitis C virus (HCV) proteins in the liver
      cells of patients with acute hepatitis C (AHC) and their association with the
      course and outcome of the disease were studied. AHC protein expression in the
      cryostat liver sections from 20 patients with AHC was estimated by
      immunohistochemical assay using original monoclonal antibodies to 5 HCV proteins
      (core, NS3, NS4A, NS4B, and NS5A). The results of HCV detection in the patients
      were compared with their biochemical, clinical, and morphological findings. HCV
      proteins were totally revealed in the livers of all the patients, individual
      proteins were identified with a frequency of 89-95%, which is significantly more
      than those in patients with chronic hepatitis C. The hepatic expression of core
      protein was shown to inversely correlate with the duration of an acute period.
      There was a direct relationship between the accumulation of core, NS3, and NS5A
      proteins and the liver tissue damage caused by stepwise necrosis rather than
      intralobular necrosis. The presumed convalescence was ascertained to be
      associated with the larger count of hepatocytes containing the proteins NS4A and
      NS3 early after AHC manifestation.

PMID- 16104518
TI  - [Biological properties of HIV-1 variants circulating among drug users in Russia].
AB  - Human immunodeficiency virus type 1 variants belonging to subtype A, as well as
      recombinant gaga/engvB variants, derived from HIV-infected patients living in the
      Moscow and Perm Regions, were isolated and characterized. Intravenous
      administration of psychoactive drugs was a major risk factor of the infection for
      all the patients. All the examined isolates of HIV-1 types A and A/B were shown
      to be characterized by a low virus-specific activity and to be used as secondary
      CCR5 and CXCR4 protein receptors. The findings suggest that the domination of
      subtype A variant in this risk group is unassociated with fundamental differences
      in biological properties between the isolates of this subtype and recombinant
      viruses.

PMID- 16104519
TI  - [Khurdun virus, a presumably new RNA-containing virus associated with coots
      (Fulica atra), isolated in the Volga river delta].
AB  - The prototype strain LEIV-Ast 01-5 of the unclassified enveloped RNA-containing
      Khurdun virus, less than 220 nm in size, which is widely distributed among coots
      (Fulica atra) in the Volga River delta, was deposited on November 4, 2004, at the
      State Virus Collection (SVC # 992). The virus was isolated annually (2001-2004)
      with a frequency of 2.3-8.5% (mean 6.3%) when examining 348 coots caught in the
      lower and middle zones of the Volga River delta. Virological examinations used
      mixed pools of the brain and spleen to inoculate neonatal albino mice and the
      cellular line Vero-E6. One strain was isolated from a pygmy cormorant
      (Phalacrocorax pygmaeus). The virus could not be isolated from other species of
      1080 birds, 20 hares, 140,000 mosquitoes of 5 predominant species, and 6,700
      Hyalomma marginatum ticks. Any antigenic relationship of the virus with all the
      viruses early isolated in the Northern Caspian Sea region has not been found.
      ELISA has been developed to detect and identify Khurdun virus antigen.

PMID- 16104520
TI  - [Genetic variety of influenza A virus in the populations of wild birds in the
      south of Western Siberia].
AB  - Influenza A virus variants belonging to H3 and H4 subtypes were isolated from
      wild ducks inhabiting in the south of Western Siberia. Phylogenetic analysis of
      hemagglutinin (HA) gene of these viruses has revealed that H3 isolates are
      closely related to those isolated from the bird inhabiting in West Europe
      (A/Teal/Germany/wv01r/01, A/Duck/Ukraine/1/63) and China (A/Aquatic bird/Hong
      Kong/399/99); and those isolated from the birds inhabiting in Germany
      (A/Garganey/Germany/wv157k/01, A/Teal/Germany/wv153k/01). Thus, closely related
      influenza A virus variants circulate in the populations of the wild birds
      inhabiting in greatly spaced regions of Eurasia.

PMID- 16104521
TI  - [Effects of antiviral agents on the reproduction of avian influenza virus A/H5
      isolated in Russia].
AB  - The antiviral agents rimantadine, ribavirine, and tamiflu were tested for the
      effects on the reproduction of avian influenza virus A/H5 in in vitro
      experiments. The findings evidence the selective inhibitory effect of these
      agents on the reproduction of these viruses in the cultured MDCK cells.

PMID- 16104522
TI  - [Intranasal infection in mice inoculated with cowpox virus strain EP-2 isolated
      from the elephant].
AB  - The specific features of reproduction of EP-2 strain of cowpox virus (CPV) were
      studied in intranasally infected BALC/C mice by light and electron microscopy.
      Virus replication was found in the ciliated, intercalary, basal, and goblet cells
      (the nasal respiratory area), basal and supporting cells (the nasal olfactory
      area), ciliated, intercalary, goblet cells (the tracheal and bronchial
      epithelium), and collagen-producing, Schwann's, endothelial, smooth muscle, and
      adventitial cells. It has been shown that the CPV strain EP-2 locally replicates
      in the nasal cavity, trachea, and large bronchi and that there is no generalized
      infection.

PMID- 16104523
TI  - [The clinical features and the structural and functional status of the liver in
      chronic viral hepatitis B concurrent with superinvasion opisthorchiasis].
AB  - Clinical manifestations of chronic viral hepatitis B (CVH-B) in replicative phase
      in patients with superinvasive opisthorchosis comprise the asthenic-vegetative
      syndrome, pain syndrome, dyspepsia (53.3% of cases) and hepatomegaly (46.7% of
      cases). Superinvasive opisthorchosis, when combined with CVH-B, stimulates the
      cytolysis of hepatocytes and the intensity of inflammation; it also shapes the
      fibrosis of the liver, which complicates the course of viral infection and its
      outcome.

PMID- 16104524
TI  - [Photodynamic inhibition of infection caused by herpes simplex virus type 1 in
      the cultured cells, by using 5-aminolevulinic acid-induced porphyrins].
AB  - On simulating infection caused by different herpes simplex virus type 1 (HSV-1)
      variants responsive and unresponsive to the drugs acyclovir and phosphonoacetic
      acid in the cultured Vero and C6 cells has revealed the higher ability of target
      cells to accumulate 5-aminolevulenic acid (ALA)-induced endogenous porphyrins,
      which determines the selectivity of their photo damages. Optimal conditions have
      been defined for all the studied HSV-1 variants to show a virus-inhibiting effect
      upon photodynamic exposure of infected and ALA-treated cell cultures.

PMID- 16104525
TI  - [The results of the 10th National Conference on Topical Aspects of Virology in
      Mongolia (Ulan-Bator, November 25, 2004)].

PMID- 16104526
TI  - [Clinical significance of Cobas Amplicor HCV Monitor test v 2.0 for quantifying a
      wide range of serum HCV-RNA in patients with chronic hepatitis C].
AB  - Recently, we evaluated the clinical significance of a new assay, the semi
      automated Cobas Amplicor HCV Monitor test v 2.0 (Roche, Cobas-HIGH-RANGE assay),
      for quantifying serum hepatitis C virus RNA throughout a wider range than the
      traditional assay, Amplicor GT HCV Monitor test v 2.0 (GT-ORIGINAL assay). We
      compared the results of the Cobas-HIGH-RANGE assay with results of the GT
      ORIGINAL assay. This study was conducted on serum from 91 patients with chronic
      hepatitis C at the Gastroenterological Center, Yokohama City University Medical
      Center. The percent coefficient of variation (CV) for the within-run and between
      run reproducibility of the Cobas-HIGH-RANGE assay ranged from 0.7 to 2.3% and
      from 1.3 to 2.0%, respectively. The Cobas-HIGH-RANGE assay exhibited a linear
      range extending from 5 to 5000 KIU/ml. The values for all 17 samples determined
      as less than 0.5 KIU/ml by the GT-ORIGINAL assay were also determined as less
      than 5 KIU/ml by the Cobas-HIGH-RANGE assay. For the 48 samples with values of
      0.5 to 850 KIU/ml determined by the GT-ORIGINAL assay, the values obtained by
      these two assay methods were significantly correlated (r2 = 0.9117, y = 1.0667x
      0.0801, p < 0.001), but the values of HCV-RNA determined by the Cobas-HIGH-RANGE
      assay were significantly (p < 0.05) higher than those determined by the GT
      ORIGINAL assay. Consequently, these data indicate that the HIGH-RANGE assay is a
      useful alternative assay method for measurement of HCV-RNA instead of the
      ORIGINAL assay, and that the HIGH-RANGE assay could be a useful tool for
      monitoring the efficacy of antiviral treatment.

PMID- 16104527
TI  - [Assessment of immunotoxicity of irinotecan determined by the novel method, by
      which productivity of TNF-alpha from whole blood is stimulated by
      lipopolysaccharide].
AB  - Irinotecan hydrochloride shows much different responses in each patient, and it
      has severe adverse effects. Therefore, a sensitive marker for the side effect of
      irinotecan on immunotoxicity may be able to prevent the severe complications by
      the early detection. We have recently developed a method to assess the
      immunotoxicity by measuring the productivity of TNF-alpha from whole blood
      containing monocytes when stimulated by lipopolysaccharide. By using this method,
      the effects of continuous low-dose irinotecan therapy on immunotoxicity were
      assessed in 10 patients with advanced gastric or colon cancer. When compared this
      method with the others such as white blood cell count, lymphocyte blastoid
      transformation by phytohem agglutinin (PHA), and natural killer cell activity in
      terms of the sensitivity, immunotoxicity by this method was found earlier than
      the other methods. Because our original method is easy to perform and sensitive
      as compared to the conventional methods, it can be widely used as one of the
      laboratory tests useful for patients treated with immunosuppressive agents.

PMID- 16104528
TI  - [Age- and sex-specific reference intervals for 10 health examination items: mega
      data from a Japanese Health Service Association].
AB  - OBJECTIVE: To determine age- and sex-specific reference intervals for 10 health
      examination items in Japanese adults. METHODS: Health examination data were
      accumulated from 24 different prefectural health service associations affiliated
      with the Japan Association of Health Service. Those who were non-smokers, drank
      less than 7 days/week, and had a body mass index of 18.5-24.9kg/m2 were sampled
      as a reference population (n = 737,538; 224,947 men and 512,591 women). After
      classified by age and sex, reference intervals for 10 health examination items
      (systolic blood pressure, diastolic blood pressure, total cholesterol,
      triglyceride, glucose, uric acid, AST, ALT, gamma-GT, and hemoglobin) were
      estimated using the parametric and nonparametric methods. RESULTS: In every item
      except for hemoglobin, men had higher reference intervals than women. Systolic
      blood pressure, total cholesterol, and glucose showed an upward trend in values
      with increasing age. Hemoglobin showed a downward trend in values with increasing
      age. Triglyceride, ALT, and gamma-GT reached a peak in middle age. Overall,
      parametric estimates showed narrower reference intervals than non-parametric
      estimates. CONCLUSION: Reference intervals vary with age and sex. Age- and sex
      specific reference intervals may contribute to better assessment of health
      examination data.

PMID- 16104529
TI  - [Consulting work cited in the hospital laboratory annual progress report of the
      laboratory information and consulting work and its role in Toyama Medical and
      Pharmaceutical University Hospital].
AB  - Recently, it is difficult for general patients to understand clinical inspection.
      Therefore we opened the laboratory information and consulting office (called
      Kensa Yorozu Consulting Room) from April, 2004. It is most characteristic that
      our office is managed by a clinical laboratory physician. A full time-specialized
      doctor who is belong to clinical laboratory, is stationed in the office. Duties
      contents of our office are consultation, publishing laboratory report and
      information, education and the clinical studies. We don't limit a person of
      consultation in particular. We accept consultations for 24 hours by coming our
      office, telephone, Fax or E-mail. The amount of consultations is about 5-10 per
      one month. The contents are suggesting inspection plan, explanation of
      pathophysiologic information based on clinical inspect result and so on. The
      examples compiled it into a database and maintains and their answers information.
      Because there are clinical laboratory physicians in this office, there are merits
      that follow. As for the medical technologist, it was not interfered with routine
      duties. For doctors and co-medical staffs, it is possible for detailed arguments
      to the diagnosis and treatment considered the condition of a patient and a
      characteristic of laboratory method. Doctors of outside can talk with us by
      telephones or emails easily. For patients, they can smoothly talk about their
      diseases with their physicians knowing more laboratory information. More medical
      stuffs need our office, because there are many repeaters although the total
      number is small. Therefore it is important that we let everybody know about our
      works and that we make good communication environment to talk easily, keeping
      privacy. We want to compile and share database of laboratory information. Then we
      can contribute to the area medical care.

PMID- 16104530
TI  - [Definition and mechanism of drug-induced thrombocytopenia].
AB  - Drug-induced thrombocytopenia is common, but most previous reports do not present
      evidence for drugs as a definite or probable cause of the thrombocytopenia. The
      important diagnostic issue is to distinguish between drug-induced
      thrombocytopenia and idiopathic thrombocytopenic purpura, because the latter
      diagnosis requires the exclusion of other causes of thrombocytopenia. Drug
      induced thrombocytopenia includes at least three mechanisms, such as marrow
      suppression, immunological, and nonimmunological thrombocytopenia. In
      immunological thrombocytopenia, demonstration of drug-dependent antiplatelet
      antibodies was included as evidence confirming the causal role of a drug.
      However, there are no standard assays for drug-dependent antiplatelet antibodies,
      no standard criteria for distinguishing positive from negative results, and no
      data on the sensitivity and specificity of these assays based on clinical
      criteria for a causal relation. Nonimmunological thrombocytopenia includes
      heparin-dependent thrombocytopenia and thrombotic thrombocytopenic purpura.

PMID- 16104531
TI  - [Heparin-induced thrombocytopenia (HIT): pathogenesis, laboratory test, and
      treatment].
AB  - Heparin-induced thrombocytopenia(HIT) due to immunological mechanisms is known as
      an important adverse reaction to heparin treatment, and heparin treatment should
      be applied while keeping in mind the risk of onset of HIT 5-14 days after the
      initiation of heparin. The presence of HIT had not been fully recognized in
      clinical practice in Japan despite the management of HIT being well confirmed in
      Western countries. Recognition of HIT has increased since argatroban, a direct
      thrombin inhibitor, obtained the approval of the FDA for prevention and treatment
      of HIT. Although the incidence of HIT in Japan has not yet been clarified, there
      is some evidence that HIT is encountered in critically ill patients undergoing
      heparin anticoagulation. Clinical diagnosis of HIT is performed by means of
      thrombocytopenia of a drop of 50% or 100 x 10(30/microl for 5 -14 days after
      starting heparin treatment. Confirmatory laboratory tests examine whether the
      patients have antibodies against heparin/PF4 complexes or not. Two assay tests
      for detecting heparin/PF4 complex antibodies are available in Japan. As a
      functional test, the heparin-induced platelet aggregation method is easily
      performed and the result is obtained in a short time. The result of the test has,
      however, been misleading due to the selection of donors. Low platelet activity of
      the donors on the addition of heparin induces a negative response in spite of
      positive antibodies in the sample. Before testing samples, it is important to
      check heparin reactivity of the donor's platelets. Enzyme immunoassay detecting
      the antibodies is available as a commercial kit. Sensitivity obtained by enzyme
      immunoassay is very high and often introduces false-positives. Careful attention
      to interpretation of the result is required. Treatment of HIT should be started
      at the time of recognition of thrombocytopenia while antibody testing for HIT is
      performed. As an alternative anticoagulant to heparin, argatroban should
      immediately be applied to avoid complication of thrombosis. Thrombocytopenia and
      hypercoagulability quickly recover to the preheparin level by the appropriate use
      of argatroban.

PMID- 16104532
TI  - [Clinical features and laboratory findings of thrombotic thrombocytopenic purpura
      associated with ticlopidine].
AB  - Ticlopidine is an antiplatelet agent that interferes with platelet membrane
      function by inhibiting adenosine diphosphate-induced platelet activation. It is
      used in an increasing number of cases of cerebrovascular disease, unstable
      angina, coronary artery stenting, and peripheral vascular diseases. It has rare
      but serious adverse reactions, including thrombotic thrombocytopenic purpura
      (TTP). TTP is a life-threatening disease, characterized by Moschcowitz's pentad:
      thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurological
      signs, renal failure, and fever. Recent advances in elucidating the proteolytic
      processing of plasma von Willebrand factor (VWF) multimers have established
      assays for VWF-cleaving protease (VWF-CP) activity and its
      inhibitor(autoantibodies). These assays apparently demonstrated that TTP patients
      have defective enzymatic activity with or without presence of the inhibitor. VWF
      CP is now identified as a metalloproteinase belonging to the ADAMTS (A
      Disintegrin And Metalloproteinase domain, with ThromboSpondin type 1 motif)
      family, termed ADAMTS13. Cases of ticlopidine-associated TTP were first reported
      in 1991. This complication occurs in 1 in 1600 to 1 in 5000 patients who receive
      ticlopidine. It is known that they develop TTP within 2 to 8 wk of starting
      ticlopidine treatment and show severely deficient of ADAMTS13 activity with the
      presence of the inhibitor. These results suggest that ticlopidine or its
      metabolites induce the production of autoantibodies against ADAMTS13. As
      treatment, discontinuation of ticlopidine therapy and rapid initiation of plasma
      exchange is effective: the majority of patients completely recover and relapse is
      uncommon. It is thus recommended that physicians should perform complete blood
      count every 2 weeks for 12 weeks for rapid diagnosis. Physicians and patients
      should be aware of this fatal but curable complication of ticlopidine therapy.

PMID- 16104533
TI  - [Development and application of a new ADAMTS13 assay for TTP diagnosis].
AB  - A plasma glycoprotein, von Willebrand factor (VWF), is essential for normal
      platelet aggregation. In healthy individuals, the homo-multimeric forms (VWF
      multimers) are partially cleaved by a plasma metalloprotease, ADAMTS13.
      Congenital or acquired deficiency of ADAMTS13 activity leads to the accumulation
      of hyperactive large VWF multimers, inducing a life-threatening disease,
      thrombotic thrombocytopenic purpura (TTP). As measuring ADAMTS13 activity is
      important in TTP diagnosis, a number of assay methods have been developed in the
      past few years. However, the time and skill required for these methods prohibited
      the progress of clinical usage. Recently, we have developed a fluorescence
      resonance energy transfer (FRET) assay for ADAMTS13 activity. A synthetic 73
      amino-acid peptide, FRETS-VWF73, which is now commercially available, is used as
      a substrate. Cleavage of this peptide between two modified residues relieves the
      fluorescence quenching in the intact form. Incubation of FRETS-VWF73 with normal
      plasma quantitatively increased fluorescence over time, while TTP-patient plasma
      had little or no effect. The measurement can be achieved within a one-hour period
      using a 96-well format in commercial plate readers with common filters. The FRET
      assay will be useful not only for TTP diagnosis but also characterization of
      thrombotic microangiopathies.

PMID- 16104534
TI  - [EDTA-dependent pseudothrombocytopenia: clinical aspects and laboratory tests].
AB  - EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is a phenomenon caused by EDTA
      dependent anti-platelet antibody. This antibody induces platelet agglutination in
      vitro, resulting in a decrease in platelet counts. It is necessary for clinicians
      to consider the possible presence of PTCP in cases of patients having low
      platelet counts without any hemorrhagic tendency. In this article, we describe
      some aspects of EDTA-PTCP including, (1) characteristics of platelet
      agglutination, (2)possible mechanisms for antibody production, (3) several
      methods to determine the true platelet number, and also (4) a few similar
      phenomena induced by antibodies independent of EDTA.

PMID- 16104535
TI  - [Examination and treatment for dilutional thrombocytopenia].
AB  - Massive transfusion is defined as transfusion of more than total blood volume
      within 24 hours. There are several adverse effects associated with massive
      transfusion, and dilutional thrombocytopenia is known as one of the major adverse
      effects. Dilutional thrombocytopenia is caused by platelet loss out of the body
      and platelet dilution with replaced red cells and crystalloids. Volume of blood
      loss or replaced volume is a good indicator of dilutional thrombocytopenia, and
      previous reports suggest that severe thrombocytopenia doesn't occur before
      replaced volume surpasses over one hundred and fifty percent of total blood
      volume. Recently, an automated blood cell counter has spread and platelet count
      is available in a short time, even at night. To treat the patient with dilutional
      thrombocytopenia, platelet count is very helpful to decide when to start platelet
      transfusion. When platelet count decreases as low as 50,000/mm3, platelet
      transfusion should be considered. Nowadays, dilutional thrombocytopenia is less
      frequent complications of massive transfusion than before, because platelet
      transfusion tends to be performed before platelet count fall to the critical
      point. Thus, exceeded platelet transfusion might become another problem after
      massive transfusion.

PMID- 16104536
TI  - [Appendix: putative drug list of drug-induced thrombocytopenia].

PMID- 16104537
TI  - [Diagnostic tests approved by the Ministry of Health and Welfare].

PMID- 16104538
TI  - [Appropriate dose of isobaric bupivacaine with fentanyl in spinal anesthesia for
      cesarean section].
AB  - BACKGROUND: Spinal anesthesia combined with fentanyl is commonly used for
      cesarean section. We studied the appropriate dose of isobaric bupivacaine for
      spinal anesthesia when combined with a fixed dose of 20 microg fentanyl. METHODS:
      Forty-seven women scheduled for cesarean section were allocated into four-groups
      according to the dose of 0.5% isobaric bupivacaine with 20 microg fentanyl; 1.0
      ml (n=5), 1.5 ml (n=11), 2.0 ml (n=11), and 2.5 ml (n=20). RESULTS: The
      requirement of epidural anesthesia for pain relief or muscle relaxant was less in
      the 2.0 ml and 2.5 ml groups than the other groups. However, dyspnea due to high
      spinal anesthesia developed in 3 subjects out of 20 in the 2.5 ml group.
      CONCLUSIONS: Two ml of 0.5% isobaric bupivacaine was the most appropriate dose
      for cesarean section, when combined with 20 microg of fentanyl.

PMID- 16104539
TI  - [Pressor responses to inhalation of isoflurane during induction of anesthesia and
      subsequent tracheal intubation].
AB  - BACKGROUND: Marked hypertension may occur during induction of isoflurane
      anesthesia. The hemodynamic responses to mask ventilation using isoflurane and
      subsequent tracheal intubation were evaluated. METHODS: In 26 ASA physical status
      I patients, anesthesia was induced with thiamylal followed by mask ventilation
      with 0.5% isoflurane in oxygen. Isoflurane concentration was increased to 4% in 2
      min, and the trachea was intubated after 3 min of ventilation with 4% isoflurane.
      Blood pressure (BP) and heart rate (HR) were recorded every minute from induction
      of anesthesia. RESULTS: In 9 patients, systolic BP before intubation increased
      significantly to more than 10 mmHg (26 +/- 16%) compared before induction, but
      decreased (-7 +/- 7%) in the others after a transient slight increase. Tracheal
      intubation induced a marked increase in BP in all patients, but there was a
      negative correlation between the isoflurane-induced increase in BP and that
      induced by intubation. Tachycardia was seen in all patients regardless of the
      values of BP. CONCLUSIONS: Inhalation of 4% isoflurane during induction of
      anesthesia induces lasting hypertension in some patients and this pressor
      response has no relation with the tachycardia. Tracheal intubation induced a
      larger increase in blood pressure in the isoflurane-induced hypertensive
      patients, but the increase is within the limits of that seen in patients without
      pressor response to isoflurane.

PMID- 16104540
TI  - [Four cases of extrapyramidal reactions to epidural droperidol administration].
AB  - Continuous epidural administration of droperidol at 2.5 mg x day(-1) or less was
      performed in 837 patients after surgery. In 4 of these patients, an
      extrapyramidal reaction occurred. Patient 1 was a 10-year-old girl who developed
      the symptom 29 hours after the start of administration, with a total dose of 3.0
      mg. Patient 2 was a 16-year-old girl in whom the symptom occurred 24 hours after
      the start, with a total of 5.3 mg. Patient 3 was a 22-year-old female with the
      symptom occurring 26 hours after the start, with a total of 5.2 mg. Patient 4 was
      a 74-year-old female in whom the symptom occurred 24 hours after the start, with
      a total of 1.3 mg. With respect to the age distribution, the total of 837
      patients consisted of 16 patients aged 10 to 19 years, 85 patients aged 20 to 29
      years, 91 patients aged 30 to 39 years, 90 patients aged 40 to 49 years, 77
      patients aged 50 to 59 years, 148 patients aged 60 to 69 years, 240 patients aged
      70 to 79 years, 97 patients aged 80 to 89 years, and 9 patients aged 90 to 99
      years. Extrapyramidal reactions related to epidural administration may readily
      develop at younger ages.

PMID- 16104541
TI  - [Anesthetic management of radical nephrectomy using cardiopulmonary bypass in
      patients with vena caval or atrial extension of renal cell carcinoma].
AB  - We experienced three cases of anesthesia for radical nephrectomy using
      cardiopulmonary bypass in patients with vena caval or atrial extension of renal
      cell carcinoma. Pulmonary thromboembolism (PTE) did not occur. One patient with
      preoperative hepatorenal dysfunction died of multiple organ failure. Other two
      patients were discharged in good condition. We must pay attention to treatment of
      intraoperative PTE and massive hemorrhage, prevention of organ damage, and
      presence of preoperative organ dysfunction.

PMID- 16104542
TI  - [Effects of neutrophil elastase inhibitor on postoperative cytokine levels in
      patients after esophagectomy].
AB  - BACKGROUND: The purpose of this study is to examine the effects of neutrophil
      elastase inhibitor on postoperative cytokine levels in patients after
      esophagectomy. METHODS: Fifteen patients were divided into two groups; group 1: 9
      patients receiving neutrophil elastase inhibitor (0.2 mg x kg(-1) x hr(-1) from
      the admission to ICU to extubation), group 2: 6 patients as a control. We
      measured neutrophil elastase activity, interleukin 1-beta, interleukin 6 and
      interleukin 8 preoperatively, just after the admission to ICU, and 24, 48 and 72
      hours after the surgery. RESULTS: There were significant differences in
      neutrophil elastase activity and interleukin 8 in group 1 24 hours after the
      surgery, compared with those in group 2. The time necessary for mechanical
      ventilation in group 1 was shorter than that in group 2 (group 1: 44.7 +/- 24.7
      hrs, group 2: 112.8 +/- 90.3 hrs, P = 0.048). CONCLUSIONS: The administration of
      neutrophil elastase inhibitor may be useful for patients after esophagectomy to
      reduce overexpression of plasma cytokine levels after surgery.

PMID- 16104543
TI  - [Cardiovascular effects of human atrial natriuretic peptide during pediatric
      renal transplantation].
AB  - BACKGROUND: We evaluated the cardiovascular effects of human atrial natriuretic
      peptide (hANP) in the pediatric recipients undergoing renal transplantation.
      METHODS: Anesthesia was maintained by inhalation of nitrous-oxide and isoflurane
      in oxygen. Intravenous infusion of hANP at a rate of 0.05 microg x kg(-1) x min(
      1) was started on the anastomosis of the renal artery after the fresh frozen
      plasma had been loaded to achieve PCWP above 17 mmHg. We examined cardiovascular
      changes by using a pulmonary artery catheter and transesophageal
      echocardiography. The measurements were done before and after 15 minutes of hANP
      infusion. RESULTS: An increase in CI and a reduction in PCWP were significant.
      CONCLUSIONS: The low-dose infusion of hANP was useful in pediatric recipients
      undergoing renal transplantation for the optimal anesthetic care in view of the
      improvement of cardiovascular functions.

PMID- 16104544
TI  - [Anesthetic management for two cases of living related small bowel
      transplantation].
AB  - Isolated small bowel transplantation allows patients with irreversible small
      bowel failure to be weaned from total parenteral nutrition (TPN). We reported the
      first two cases of anesthesia for living related donor small bowel
      transplantation in our hospital. They had required long-term TPN. This resulted
      in thrombosis of the major blood vessels which critically restricted vascular
      access available for TPN, leading to a life-threatening condition for the
      patients. In patients with known difficult vascular access, performing a magnetic
      resonance imaging before surgery to evaluate patency of central veins seems
      reasonable, as well as inserting a central catheter before the surgical
      procedure. Graft reperfusion may cause hemodynamic instability due to changes in
      potassium, acid-base status as the preservative solution is flushed out of the
      implant. Hemodynamic, respiratory parameters and urinary output were well
      preserved throughout the procedure. Besides, a transitory increase in potassium
      following graft revascularization and biochemical changes were small. Anesthetic
      management requires comprehensive preoperative assessment and sufficient
      management without interfering with intestinal function, optimizing splanchnic
      perfusion to ensure implant viability.

PMID- 16104545
TI  - [Preliminary report: effects of artificial blood on hypoxic pulmonary
      vasoconstriction].
AB  - BACKGROUND: We examined the effects of artificial blood on hypoxic pulmonary
      vasoconstriction (HPV). METHODS: Pump-perfused rabbit lungs were reperfused and
      ventilated with a mixture of 21% O2, 5% CO2, and balance N2. HPV was induced by
      reduction of O2 concentration from 21 to 3% for 5 min. Pulmonary arterial
      pressure (PAP) was measured using a low-pressure transducer. Two perfusion
      solutions, (1) a mixture of autologous red blood cells and physiological salt
      solution supplemented with 5% albumin and (2) artificial red blood cells
      (liposome-encapsulated hemoglobin) and physiological saline supplemented with 5%
      albumin, were made. Using each solution, HPV was evaluated by PAP increase with
      and without inhalation of nitric oxide (NO). RESULTS: (1) With both autologous
      and artificial perfusion solutions, hypoxic stimulation (HS) increased PAP. (2)
      With the autologous solution, NO inhalation suppressed the HS-induced PAP
      increase, but with the artificial solutions no such a phenomenon was observed.
      CONCLUSIONS: NO inhalation failed to suppress HPV with the artificial solution,
      probably since the liposome-encapsulated hemoglobin strongly inactivated NO.

PMID- 16104546
TI  - [General anesthesia for a patient with Noonan's syndrome and long-term
      antidepressant therapy].
AB  - Noonan's syndrome is associated with cardiovascular, spinal and airway
      abnormalities. We experienced general anesthesia for a patient with Noonan's
      syndrome and long-term antidepressant therapy. A 42-year-old man was scheduled
      for radical operation for ventral hernia. He had been diagnosed as Noonan's
      syndrome by his facial and spinal abnormalities. He was intubated under
      bronchofiberscopy for his previous general anesthesia. He had received
      amitriptyline 50 mg daily for ten years. Anesthesia was induced with midazolam 3
      mg, fentanyl 50 microg, droperidol 1.25 mg. He was intubated under
      bronchofiberscopy after topical lidocaine 400 mg application. Then thiopental 125
      mg and sevoflurane 0.4% was administered. Blood pressure decreased after
      intubation to 70/40 mmHg, which was resistant to ephedrine 10 mg. After starting
      surgery, blood pressure increased to 100/70 mmHg and was stable until the end of
      surgery. This patient presented a problem of difficult intubation as Noonan's
      syndrome and had a history of a long-term use of antidepressant, which might
      induce sympathomimetic resistant hypotension.

PMID- 16104547
TI  - [The consumption of nitrous oxide used for general anesthesia has been markedly
      reduced in recent years in our institute].
AB  - We reported the incidence of general anesthesia using nitrous oxide (N2O), one of
      the greenhouse gases in the atmosphere, and the total consumption of N2O in our
      institute in 1990, 1995, 2000, and 2004. Nitrous oxide was used in 93%, 97%, 89%,
      and 49% of general anesthesia in 1990, 1995, 2000, and 2004, respectively. The
      consumption of N2O was markedly reduced from 1314 kl in 1990 to 413 kl in 2004.
      In 1996, propofol was introduced for total intravenous anesthesia. Moreover, low
      flow anesthesia (total gas flow not exceeding 2 l x min(-1)) was vigorously
      introduced. We consequently decreased the amount of N2O consumed during
      inhalational anesthesia despite the increase in cases of general anesthesia in
      recent years.

PMID- 16104548
TI  - [Anesthetic management for a patient with multiple sclerosis].
AB  - A 49-year-old woman with multiple sclerosis (MS) received emergency laparotomy
      for panperitonitis. She had been suffering from MS for 13 years, and her main
      clinical symptoms were disorders in sight, walking and touch sensation below T 7.
      We used propofol and fentanyl for induction and maintained anesthesia with
      nitrous oxide, sevoflurane and additional fentanyl. Intubation was carried out
      without muscle relaxant. Train of four ratio was monitored during surgery. Thus
      the use of muscle relaxant was suppressed to the minimum requirement. Circulatory
      function was stable and no cardiovascular agent was used throughout the surgery.
      Awakening from anesthesia was smooth and exacerbation of the neurological
      abnormalities was not observed after surgery. She was transferred uneventfully to
      a recuperative hospital on the 13th postoperative day.

PMID- 16104549
TI  - [Posterior interosseous nerve palsy in a man in a lateral position for
      laparoscopic adrenalectomy--a case report].
AB  - A 51-year-old man with aldosteronism underwent laparoscopic left adrenalectomy.
      Anesthesia was induced with fentanyl 0.1 mg, propofol 140 mg and vecuronium 7 mg.
      Following endotracheal intubation, he was placed in a right lateral position with
      extension of his left side, and fixed with the Magic Bed. Canulation of the right
      radial artery was smoothly performed. Anesthesia was maintained with sevoflurane
      and thoracic epidural anesthesia (mepivacaine and ropivacaine). The operation
      lasted for 270 minutes and was uneventful. A few hours after surgery, he
      complained of inability to extend his right fingers without any sensory loss, and
      the local oppressive pain on his right forearm. Neurological examination revealed
      a posterior interosseous palsy. Symptoms improved gradually and disappeared
      completely in two months with the administration of vitamin B12 and physical
      therapy. Postoperative reproduction of the positioning of this case disclosed
      that the edge of the Magic Bed might potentially compress the posterior
      interosseous nerve at the point where the nerve is bifurcated from the radial
      nerve and travels within the supinator muscle going into the muscle again. This
      case indicated that we must be careful of nerve injuries due to devices used to
      maintain the patient in lateral position.

PMID- 16104550
TI  - [General anesthesia for a patient with asymptomatic sick sinus syndrome].
AB  - A 67-year-old man with glioblastoma was scheduled for craniotomy. Before
      anesthesia induction, asymptomatic bradycardia (40 beats x min(-1)) occurred, and
      was resistant to atropine 0.4 mg. The surgery was postponed. He was diagnosed as
      sick sinus syndrome (sinus arrest). He received implantation of a temporary
      cardiac pacemaker on the day before the rescheduled surgery. Anesthesia was
      induced with thiopental 400 mg, fentanyl 200 microg, vecuronium 10 mg and
      isoflurane 5%, and maintained with isoflurane 1-2% in oxygen 3 l x min(-1) and
      air 3 l x min(-1). Pacing mode was set to fixed rate asynchronous pacing in the
      ventricle with a rate of 50 beats x min(-1) after anesthesia induction. Surgery
      was completed in 8 hours and 45 minutes without any complications. The pacing
      wire was removed the next day. For patients with sick sinus syndrome,
      implantation of the pacemaker is indicated in case of bradycardia-tachycardia
      syndrome or with any clinical symptoms. However, a pacemaker should be implanted
      before general anesthesia even in a patient with no clinical symptoms because of
      cardiovascular instability induced by anesthesia.

PMID- 16104551
TI  - [Successful management of a patient with rhabdomyolysis and marked elevation of
      serum creatine kinase level].
AB  - We experienced successful management of a patient with severe rhabdomyolysis by
      conservative treatment. A 41-year-old man developed Stanford-A-type acute aortic
      dissection and underwent an emergent replacement of the aortic root and arch.
      After the weaning from cardiopulmonary bypass, his left femoral artery was found
      non-pulsatile, probably due to extension of the aortic dissection, and femoro
      femoral artery bypass surgery was added. Estimated ischemia time of the lower
      extremities was 7 hours. On admission to the intensive care unit (ICU), his left
      lower extremity showed signs of reperfusion injury accompanied with marked
      elevation of serum creatine kinase (12,397 IU x l(-1)) and myoglobin (19,980 ng x
      ml(-1)), and impaired oxygenation (a ratio of PaO2 to FIO2, 130 mmHg). We
      performed (1) moderately aggressive infusion treatment, (2) maintenance of
      hyperdynamic states using catecholamine, (3) diuresis therapy using atrial
      natriuretic peptide and furosemide, and (4) lung protective strategy. Although
      serum creatinine increased to 2.0 mg x dl(-1) on postoperative day (POD) 1,
      diuresis was maintained and the level of creatinine returned to normal on POD 6.
      He was extubated on POD 6 and discharged on POD 7. The early start of these
      combined therapies seems to have prevented acute renal failure without blood
      purification.

PMID- 16104552
TI  - [Transfusion-related acute lung injury: a case report].
AB  - We report a patient who was suspected of transfusion-related acute lung injury. A
      60-year-old man underwent emergency thoracotomy and hemostasis after
      pneumonectomy. The SpO2, decreased abruptly to 66% 90 minutes after transfusion
      of packed red blood cells and fresh frozen plasma. He was ventilated with 100%
      oxygen. The SPO2 returned to 100% in 3 minutes. Postoperative chest radiography
      showed diffuse pulmonary infiltrates. The pulmonary edema improved in 12 hours
      with mechanical ventilation.

PMID- 16104553
TI  - [Perioperative stroke after esophageal surgery].
AB  - A 65-year-old man received general anesthesia for extended esophagectomy with 3
      field lymph node dissection. Although he was without many risk factors for stroke
      except smoking, chest computed tomography performed preoperatively showed a small
      calcification at the origin of the left subclavian artery on the aortic arch. The
      anesthetic course was uneventful. On the first postoperative day, when the
      patient awoke from sedation, he presented with left conjugate deviation of the
      eyes and right hemiparesis. Immediate computed tomography scanning revealed
      cerebral infarction in the area of the left middle cerebral artery associated
      with hyper density indicating a thrombus. Both transthoracic echocardiography and
      carotid ultrasonography were performed to determine the cause of stroke. As a
      result, severe atheromatous stenosis of the left internal carotid artery was
      noticed, while there was neither thrombus nor shunt in the heart. Intraoperative
      cerebral emboli during surgical manipulation of the carotid artery were strongly
      suspected as a possible cause of the stroke. Preoperative carotid screening by
      ultrasonography may be advocated to identify such a patient as the present case
      with occult carotid atherosclerosis at risk for a subsequent stroke.

PMID- 16104554
TI  - [Anesthetic management for an emergency operation in a patient with von Gierke
      disease].
AB  - A 45-year-old patient with von Gierke disease was scheduled for emergency
      operation due to acute appenditis. He had a significant hepatomegaly and was on
      oral medication for hyperlipemia and hyperlithuria. General anesthesia was
      induced with thiopental and suxamethonium, and maintained with nitrous oxide,
      oxygen, sevoflurane and vecuronium. The perioperative course was uneventful,
      although the patient revealed mild metabolic acidosis.

PMID- 16104555
TI  - [Perioperative use of recombinant activated factor VII (rF VIIa) in a patient
      with hemophilia A having inhibitors].
AB  - We experienced the perioperative management of a patient with hemophilia A having
      inhibitors using recombinant activated factor VII (rF VIIa). A 55-year-old man
      was scheduled for right total hip arthroplasty. Since he developed high titer of
      VIII inhibitor, rF VIIa was utilized for the hemostatic control for "bypass
      therapy". Dosage and interval for perioperative rF VIIa administration were
      determined before the surgery with a trial injection. Just before anesthesia
      induction, rF VIIa (9.6 mg) was given and repeated every 2 hrs during surgery
      till the 2nd post operative day (POD). Thereafter, rF VIIa was repeatedly given
      in decremental steps till 5th POD. Although intraoperative bleeding was 2500 g
      and 1200 ml of RBC was transfused, post surgical bleeding was minimal and no
      adverse effect was observed. He was discharged on 46th POD without any trouble.
      Perioperative rF VIIa administration is safe and useful for hemostatic control in
      a patient with hemophilia A having inhibitor.

PMID- 16104556
TI  - [Complications related to anesthesia in the University of Occupational and
      Environmental Health Hospital].
AB  - BACKGROUND: Complications related to anesthesia remain a problem. We studied the
      incidence of complications during anesthesia in 2688 patients who had undergone
      anesthesia in the University of Occupational and Environmental Health Hospital.
      METHODS: We checked the anesthesia records retrospectively and analyzed the
      collected data for the incidence of complications during anesthesia. RESULTS: The
      total incidence of complications during anesthesia was 8.7%:5.5% related to
      circulation and 1.9% to respiration. CONCLUSIONS: Complications related to
      anesthesia should be prevented as much as possible through anesthesiologists'
      efforts in protocol development and skilled assistance.

PMID- 16104557
TI  - [Medical support for northern Iraq].
AB  - I had a chance to visit northern Iraq, as a member of a medical support program
      for Sulaimany Teaching Hospital in northern Iraq. Medical equipment and supply to
      the hospital had improved, comparing to the condition ten years before just after
      the Gulf War. What Iraqi doctors need now is to obtain new medical information or
      technique, which they could not absorb during the last ten years under economic
      sanctions. In anesthetic field, my activity was mainly to teach regional
      anesthesia or regional block, because Iraqi anesthetists have enough knowledge in
      anesthesiology. Similar support is necessary for all of Iraq.

PMID- 16104558
TI  - [Critical events in the operating room among 1,440,776 patients with ASA PS 1 for
      elective surgery].
AB  - BACKGROUND: The Japanese Society of Anesthesiologists (JSA) survey of critical
      incidents in the operating room has shown that preoperative complications are the
      leading causes of critical incidents, and affect the occurrence, severity and
      outcome of critical incidents which are due to causes other than preoperative
      complications. Causes of critical events in the operating room were examind in
      patients for elective surgery with American Society of Anesthesiologists physical
      status (ASA PS) 1. METHODS: JSA has conducted annual surveys of critical
      incidents in the operating room by sending and collecting confidential
      questionnaires to all JSA Certified Training Hospitals. From 1999 to 2002,
      3,855,384 anesthesia patients were registered. Among these, 1,440,776 patients
      with ASA PS 1 for elective surgery were analyzed. The causes of critical
      incidents were classified as follows: totally attributable to anesthetic
      management (AM), mainly to intraoperative pathological events (IP), to
      preoperative complications (PC), and to surgical management (SM). IP consists of
      coronary ischemia mainly due to coronary vasospasm, arrhythmias, pulmonary
      embolism, and other conditions. RESULTS: The incidences of cardiac arrest,
      critical incidents other than cardiac arrest and subsequent death were 9.86,
      59.41 and 3.12 per 100,000 anesthesia cases, respectively. IP and SM were
      responsible for 36.6% and 34.5% of cardiac arrest, respectively. AM and SM were
      responsible for 46.7% and 26.8% of critical incidents other than cardiac arrest,
      respectively. SM, IP and AM were responsible for 66.7%, 22.2% and 4.4% of
      subsequent deaths (within 7 postoperative days), respectively. Coronary ischemia
      and pulmonary embolism were the main causes of death due to IP. The incidences of
      cardiac arrest and death totally attributable to AM were 1.87 and 0.14 per
      100,000 anesthesia cases, respectively. Medication problems were responsible for
      48.1% of arrests, while airway/ventilation problems were for 57.2% of critical
      incidents other than arrest. Human factors (SM combined with AM) were responsible
      for 53.5%, 73.5%, and 71.1% of cardiac arrest, critical incidents other than
      arrest and death, respectively. CONCLUSIONS: Even in elective patients with good
      physical status, non-lethal incidents were not rare, and lethal incidents were
      also reported. We should pay significant attention to the following findings, and
      take some measures to overcome these problems especially related to human
      factors. Firstly, SM badly harmed some operative patients. Secondly, coronary
      vasospasm and pulmonary embolism were the main causes of death due to IP.
      Thirdly, drug administration and airway/ventilation management were the major
      causes of critical incidents totally attributable to AM. Human factors were
      responsible for 70.6% of critical incidents and 71.1% of deaths.

PMID- 16104559
TI  - [Effect of induction chemotherapy followed by surgery for bulky N2, T4 non-small
      cell lung cancer].
AB  - It is controversial that the effect of induction chemotherapy for bulky N2, T4
      non-small cell lung cancer. We examined a retrospective study to assess this
      issue. Ten patients with bulky N2, T4 disease were given bronchial arterial
      infusion consisting of cisplatin (60 mg/m2) and docetaxel hydrate (60 mg/m2)
      intravenously, followed by standardized surgical resection (group A). Thirty
      patients had pathological N2, T4 disease after surgery (group B). Pathologically
      downstaging was seen in 6 patients in group A. The overall long-term survival at
      1-, 2-year were 87.5, 87.5% in group A. The long-term survival at 1-, 2-, and 5
      year were 78.9, 49.8, 43.6% in group B. There was no statistically significant
      difference in survival between both groups (p = 0.3015). The effect of induction
      chemotherapy for bulky N2, T4 non-small cell lung cancer was not demonstrated in
      our data. We suggest that our induction chemotherapy in group A was effective on
      T4 disease. A prospective study is needed to investigate our regimen.

PMID- 16104560
TI  - [Fontan operation for tricuspid atresia with dysplasia of the right ventricular
      myocardium and absence of pulmonary valve].
AB  - We report a case of successful staged repair of tricuspid atresia with dysplasia
      of the right ventricular myocardium and absence of the pulmonary valve. The
      patient underwent the modified Blalock-Taussig shunt operation at 1 month the
      bidirectional Glenn procedure at 11 months, and the total cavopulmonary
      connection procedure using extracardiac graft at 2 years. It is important to
      prevent the left ventricular outflow tract obstruction (LVOTO) caused by the non
      functioning right ventricle when the Fontan completion. We were safely able to
      disconnect the pulmonary trunk from the right ventricle using the transesophageal
      echocardiography to evaluate the LVOTO during operation.

PMID- 16104561
TI  - [Chondrosarcoma of the chest wall].
AB  - We report 2 patients with chondrosarcoma of the chest wall. They were a 67-year
      old woman (case 1) with an anterior chest wall tumor and a 68-year-old woman
      (case 2) with a painful rib tumor. Their computed tomography (CT) both revealed
      calcified tumors. Case 1 underwent a wide resection by partial sternectomy, with
      free surgical margins. Case 2 underwent tumor resection with the posterior part
      of the 3rd rib, with positive surgical margin in the vertebral site, and received
      adjuvant radiotherapy. Both patients were pathologically diagnosed as having
      grade II chondrosarcoma. In their postoperative courses, they are free from
      recurrence. Wide resection is likely to be the key to successful management of
      chest wall chondrosarcoma.

PMID- 16104562
TI  - [Pericardial abscess by aspergillus mimicking a cardiac tumor].
AB  - We report a rare case of 34-year-old man who was diagnosed as cardiac tumor after
      therapy for acute lymphatic leukemia. Echocardiography and computed tomography
      (CT) showed that the tumor was located from the right atrium to the right
      ventricle and about 6.0 cm in diameter. Resection of the tumor was performed
      under cardiopulmonary bypass. The histological findings revealed pericardial
      abscess by Aspergillus.

PMID- 16104563
TI  - [Pulmonary large cell carcinoma contiguous to bullae with massive bullous
      hematoma and hemoptysis; with special reference to 20 cases of Japanese reports].
AB  - A 50-year-old man with continuous hemosputa and large hematoma of left upper lobe
      contiguous to bilateral emphysematous bullous disease was admitted for surgery to
      stop hemorrhage and to resect left lung hematoma and multiple bullae. Bullectomy
      and neodymium yttrium aluminum garnet (Nd-YAG) laser irradiation to bullae of
      left upper lobe performed successfully with maximum preserved pulmonary function
      of it. Pathological examination, however, revealed anaplastic carcinoma inside
      bulla of S(1+2)c with minimal invasion into adhered parietal pleura (p 3). Left
      upper lobectomy was carried out with complete mediastinal lymph node dissection
      (ND 2 b). The final pathological diagnosis was large cell carcinoma of left
      S(1+2)c with the staging pT3N0M0 and stage II. The patient lives actively in
      daily life more than 7 years without any recurrence. Clinical analysis of
      Japanese 20 cases of lung carcinoma with initial signs of hemosputa and/or
      hemoptysis contiguous to emphysematous bullae elucidate following important
      facts. Hemosputa and hemoptysis play important role for early finding and
      diagnosis of lung cancer contiguous to bullous disease, especially in patients of
      early clinical stage with or without computed tomography (CT) exams and promise
      to better surgical prognosis and survivals as compared with non hemosputa ones.

PMID- 16104564
TI  - [Evaluation of the proximal stenosis of native coronary vessels after coronary
      artery bypass grafting].
AB  - This study was designed to evaluate proximal native coronary stenosis (PNCS)
      after coronary artery bypass grafting (CABG). In 36 patients undergoing
      postoperative coronary arteriography, the PNCS bypassed with internal thoracic
      artery (ITA), saphenous vein graft (SVG) and right gastroepiploic artery (RGEA)
      progressed in 9 of 23 vessels (39%), in 15 of 28 vessels (53%), in 4 of 11
      vessels (36%), respectively. Stenosis of no grafted coronary vessels progressed
      in 3 of 26 vessels (11%). Twelve native coronary vessels (9: 99% and 3: 90%
      stenosis vessels) bypassed with grafts were obstructed. This study confirms that
      the PNCS progresses significantly by CABG just after the operation and that it
      tends to progress highly with SVG in comparison with arterial grafts such as ITA
      or RGEA. Because operative mortality for repeated CABG is approximately twice as
      high as that for primary CABG, it is important to decide whether early
      postoperative percutaneous transluminal angioplasty is needed or not, in
      considering of future graft failure and stenosis progression of the native
      coronary vessels by CABG.

PMID- 16104565
TI  - [Microwave coagulation therapy with potassium titanyl phosphate (KTP) laser
      therapy for airway stenosis from a recurrent tracheocarinal tumor].
AB  - About 2 years after right lower lobectomy for anadenocarcinoma in the right lung,
      an 80-year-old man had a reccurent tumor in tracheocarinal lymph nodes. Although
      concurrent chemoradiotherapy was performed, there was no change (NC) and the
      tumor grew back slowly. He was admitted to our hospital with exertional dyspnea
      and stridor 2 years later. The bronchoscopic microwave coagulation therapy was
      performed in the right main bronchus. After potassium titanyl phosphate (KTP)
      laser therapy had been performed in the tracheocarinal lumen, an expandable
      metallic stent was performed. The postopertive course was uneventful.

PMID- 16104566
TI  - [The tape for pulmonary artery banding].
AB  - Pulmonary artery banding remains a useful procedure for special conditions. A 3
      month-old girl diagnosed as Down syndrome with atrioventricular septal defect
      underwent pulmonary artery banding. We used polyester tape smeared with Bone Wax
      for this pulmonary artery banding. After 7 months period, the tape was easily
      dissected from surrounding tissue and removed at radical operation. Microscopic
      appearance showed that the tape was intact and no evidence of inflammation or
      mineralization. We believe Bone Wax smeared polyester tape accomplishes well as
      silicone impregnated one.

PMID- 16104567
TI  - [Atrial fibrillation after isolated coronary bypass surgery].
AB  - Postoperative atrial fibrillation (Af) remains a significant source of morbidity
      after coronary artery bypass grafting (CABG). Prophylactic therapy with beta
      adrenergic blockers or amiodarone hydrochloride is reported to reduce the
      incidence of Af. We studied the incidence of Af retrospectively and considered
      the risk factors for it. Ninety-three patients who underwent isolated CABG from
      April 2003 to March 2004 are included in this study. Postoperative Af was
      observed in 22 (25%) patients. Ten of them were operated on off-pump procedure,
      and 14 had any type of beta-adrenergic blockers preoperatively. The mean age of
      the group of postoperative Af is 69.7 +/- 9.2 years old (older than the non-Af
      group: 65.5 +/- 10 years old, p = 0.087). And the preoperative left atrial size
      was larger in the Af group than in the non-Af group (43.4 +/- 6.1 versus 40.6 +/-
      5.4mm, p = 0.064) Major embolic complication occurred in only 1 (1.1%) patient of
      non-Af group. We observed postoperative Af in 25% of patients after CABG. Older
      age and larger left atrial size may relate to the incidence of Af, and
      appropriate anticoagulant therapy and medication of beta-blockers are important
      for the patients who have such risk factors.

PMID- 16104568
TI  - [Primary lung cancer incidentally diagnosed in lung biopsy for diffuse pulmonary
      disease].
AB  - We here presented 2 cases of interstitial pneumonia with lung adenocarcinoma
      incidentally diagnosed by partially resected lung for diffuse pulmonary disease.
      CASE 1: A 78-year-old female was admitted to the hospital complaining of
      productive cough and general fatigue. The chest computed tomography (CT) revealed
      diffuse honey comb pattern in bilateral lung field especially in the right lower
      lung. Video-assisted thoracoscopic lung biopsy was performed and was diagnosed as
      diffuse spreading well differentiated adenocarcinoma. CASE 2: A 59-year-old male
      was admitted to the hospital complaining of dyspnea and general fatigue. The
      chest X-ray revealed right pneumothorax and chest CT revealed diffuse honey comb
      pattern and bullae in bilateral lung field and fibrous tumor-like lesion in the
      right middle lung. Video-assisted thoracoscopic lung biopsy was performed and was
      diagnosed as pulmonary fibrosis with papillary adenocarcinoma. CONCLUSION: It is
      important to examine carefully the specimen obtained from thoracoscopic lung
      biopsy even if interstitial pneumonia is strongly suspected.

PMID- 16104569
TI  - [Ruptured infected descending aortic aneurysm successfully treated by omentopexy
      and a rifampicin-soaked vascular prosthesis; report of a case].
AB  - A 73-year-old man was admitted for investigation of back pain, blood-stained
      sputum, and a high fever. Computed tomography (CT) showed a pseudoaneurysm in the
      descending aorta and intravenous antibiotic therapy was begun immediately after
      blood had been taken for culture. However, his temperature continued to spike
      daily, up to 38 degrees C, and his CRP was also elevated. The blood cultures were
      negative. The aneurysm ruptured and we replaced the descending aorta with a
      rifampicin (RFP)-soaked vascular prosthesis, and wrapped it with greater omentum.
      Postoperative antibiotic therapy with vancomycin hydrochloride, RFP, and amikacin
      sulfate was continued for 8 weeks. The patient recovered uneventfully. Thus, an
      infected aneurysm was effectively treated with a RFP-soaked vascular prosthesis
      and omentopexy.

PMID- 16104570
TI  - [Norwood procedure after colostomy; report of a case].
AB  - We encountered a baby who was diagnosed with anal atresia, interruption of aortic
      arch (type B), aortic stenosis, mitral stenosis, single atrium, large ventricular
      septal defects, aberrant origin right subclavian artery. We operated on him using
      the Norwood procedure after a colostomy. Aortic arch was reconstructed by
      interposing with an 8 mm graft and the right ventricular-pulmonary artery (RV-PA)
      conduit was chosen for pulmonary flow. We closed the sternum 6 days after the
      Norwood procedure. We extubated him 16 days after delayed sternal closure. There
      was no trouble with his stoma and no sign of infection. The postoperative
      echocardiography didn't show the finding which left pulmonary artery was
      stenotic, but the lung perfusion schintigraphy revealed an imbalance in the
      distribution of lung perfusion. He was discharged 70 days after undergoing the
      Norwood procedure.

PMID- 16104571
TI  - [Coronary artery bypass graftingin a patient with aortitis syndrome; report of a
      case].
AB  - We present a case of surgical treatment for a coronary lesion due to aortitis
      syndrome. A 41-year-old woman, suffering from aortitis syndrome and under
      prednisolone (PSL) therapy, underwent coronary artery bypass grafting (CABG).
      Surgical treatment was performed according to the aortic no-touch technique, but
      the patient showed a poor cardiac performance 5 days after the operation. This
      accident was resolved by increasing the PSL dose. Aortitis syndrome treated with
      PSL needs careful perioperative management besides an operative procedure.

PMID- 16104572
TI  - [Fungal endocarditis found at onset of lower limb acute aortic occlusion; report
      of a case].
AB  - Fungal endocarditis caused by Candida species is associated with high morbidity
      and mortality. A combination of surgical resection and antifungal drug therapy is
      the golden standard for treatment. We reported a case of fungal endocarditis due
      to Candida lusitaniae found at onset of lower limb acute aortic occlusion cured
      by emergency operation. This case suggests that Candida endocariditis can be
      managed medically with antifungal drug therapy in life time.

PMID- 16104573
TI  - [Optimal treatment of intrathoracic extramedullary hematopoiesis resembling
      posterior mediastinal tumor; report of a case].
AB  - Intrathoracic extramedullary hematopoiesis is a rare condition accompanying
      chronic hematologic disease. We present a case of chronic gastric ulcer in which
      a posterior mediastinal mass was diagnosed as extramedullary hematopoiesis. We
      underwent video-assisted thoracoscopic resection safely and successfully. This
      procedure is relevant and safety procedure for differential diagnosis of patients
      who have chronic anemia with asymptomatic intrathoracic tumors.

PMID- 16104574
TI  - [Left atrial thrombus in an 80-year-old woman scheduled to have an operation for
      uterus cancer; report of a case].
AB  - An 80-year-old woman was scheduled to have an operation for uterus cancer.
      Echocardiography revealed a giant mobile mass in the left atrium with a stalk at
      posterior wall of the left atrium. There was no significant mitral disease. Due
      to the risks of sudden circulatory collapse and systemic emboli, an emergency
      operation was indicated. Right side of the left atrium was opened under
      cardiopulmonary bypass following median sternotomy. The mass was attached to the
      posterior wall, 1.5 cm medial to the right upper pulmonary vein, with a thin
      stalk as diagnosed preoperatively. The mass (4.2 x 3.4 x 3.4 cm) was removed very
      easily. Pathological analysis revealed that the mass was a thrombus mixed with
      fibrin. A possible cause would be paroxysmal atrial fibrillation and/or
      hypercoagulative status due to malignancy. Anti-coagulation therapy was initiated
      postoperatively to prevent recurrence of thrombus. The patient recovered and
      discharged uneventfully.

PMID- 16104575
TI  - [Giant hemangioma in the neck extending into the mediastinum required a second
      operation after 39 years; report of a case].
AB  - An asymptomatic 69-year-old man was admitted to our hospital for an abnormal
      shadow on the chest X-ray of a medical examination. He had undergone an operation
      for a hemangioma in the neck (incomplete resection) 39 years before admission.
      Computed tomography (CT) of the neck and chest revealed an giant cystic mass in
      the neck extended into the mediastinum, severe deviation of the trachea to the
      right and fluid collection in the mediastinum. It was considered to be a giant
      hemangioma with mediastinal hemorrhage by the rupture of the tumor. After the
      large afferent and efferent vessels were identified by angiography and
      venography, we performed the resection of the tumor. Pathological examination
      confirmed the diagnosis of arteriovenous hemangioma.

PMID- 16104576
TI  - [Castleman disease in the posterior mediastinum showing atypical feature in
      computed tomography; report of a case].
AB  - A 41-year-old man was referred to our hospital because of an abnormal mass on a
      chest X-ray. An enhanced computed tomography (CT) showed a well-defined round
      mass (30 x 45 x 66 mm in diameter) that was heterogeneously enhanced owing to
      central necrotic or cystic change. A 3-dimensional CT demonstrated a couple of
      feeding arteries to the mass. The mass was completely resected through
      thoracotomy. Dissection of tight adhesion between the hypervascular mass and the
      surrounding tissues caused relative amount of hemorrhage during the surgery. The
      cystic lesion of the mass was fulfilled with brown liquid. The pathological
      examination revealed the mass as Castleman disease, and scattered cells in the
      cystic lesion.

PMID- 16104577
TI  - [Biological supramolecular systems organizing living activity].

PMID- 16104578
TI  - [Chemical studies on the reaction mechanism of cytochrome C oxidase].

PMID- 16104579
TI  - [ATP synthase: highly organized molecular structure and its marvelous function].

PMID- 16104580
TI  - [What is the driving force for the rotation of ATP synthase F1?].

PMID- 16104581
TI  - [Structural studies on the photosynthetic electron transfer complexes].

PMID- 16104582
TI  - [Structure and function of photosystem II complex].

PMID- 16104583
TI  - [Bacterial photosynthetic unit: light-harvesting and reaction center complexes].

PMID- 16104584
TI  - [Structure, function and structural organization of proteasome].

PMID- 16104585
TI  - [Substrate-channelling mechanism of a fatty acid beta-oxidation multienzyme
      complex].

PMID- 16104586
TI  - [G protein-coupled receptors as sensors of the cell].

PMID- 16104587
TI  - [IP3 receptor and calcium signaling].

PMID- 16104588
TI  - [Interaction between rhodopsin intermediates and G-protein transducin on the
      outer segment membrane of photoreceptor cells].

PMID- 16104589
TI  - [Dynamic regulation of receptor transmembrane domain assembly during signal
      transmission across the plasma membrane].

PMID- 16104590
TI  - [super-molecular interaction of p47(phox): a regulatory protein of superoxide
      producing system in phagocytes].

PMID- 16104591
TI  - [Biological significance of DNA quadruplex and its unfolding by protein in
      replication, recombination and telomere elongation].

PMID- 16104592
TI  - [Structural biology of transcription on eukaryotic chromatin].

PMID- 16104593
TI  - [Dynamic supramolecular complex of aminoacyl-tRNA synthetases controlling
      cellular life and death].

PMID- 16104594
TI  - [Structure and functions of a calcium pump].

PMID- 16104595
TI  - [Structure and function of water channels].

PMID- 16104596
TI  - [Single particle analysis of sodium channel: 3D reconstruction from electron
      microscope images].

PMID- 16104597
TI  - [Subtype-specific and ER lumenal environment-dependent regulation of IP3 receptor
      type 1 by ERp44].

PMID- 16104598
TI  - [Structural basis of the K+ channel inhibition by pore-blocking toxins, revealed
      by NMR].

PMID- 16104599
TI  - [Structural basis of mitochondrial import].

PMID- 16104600
TI  - [Structure of ubiquitin-recognition motifs and higher structures of polyubiquitin
      chains].

PMID- 16104601
TI  - [Crystal structure of heme binding protein, an autotransporter hemoglobin
      protease from pathogenic Escherichia coli].

PMID- 16104602
TI  - [Structure, function and self-assembly of the bacterial flagellum].

PMID- 16104603
TI  - [Universal joint of biological supramolecule: mechanism of bacterial flagellar
      hook investigated in silico].

PMID- 16104604
TI  - [Structure and infection mechanism of bacteriophages].

PMID- 16104605
TI  - [Assembly merchanism of rice darf virus].

PMID- 16104606
TI  - [Functional expression system for bovine-human hybrid cytochrome oxidase].

PMID- 16104607
TI  - [Development of a novel system for the highly sensitive monitoring of molecular
      interactions with the application of cell-free protein synthesis techniques].

PMID- 16104608
TI  - [Solution NMR approaches for the analyses of bio-supramolecules].

PMID- 16104609
TI  - [The SAIL method: a new NMR approach for larger protection].

PMID- 16104610
TI  - [Interface prediction for class A GPCR oligomers].

PMID- 16104611
TI  - [Analysis of intracellular membrane protein function by small molecule-based
      chromophore-assisted laser inactivation].

PMID- 16104612
TI  - [Detergents for crystallization of membrane protein].

PMID- 16104613
TI  - [Stratification scores for risk in the context of acute coronary syndromes].
AB  - The patients presenting acute coronary syndrome with or without ST segment
      elevation form a heterogeneous population and thus the short and long-term risk
      of death or recurrent ischemic events can vary considerably. During ACS without
      ST elevation (unstable angina and non-ST elevation MI), the evaluation of risk is
      an essential step in the management of such patients, because it determines
      ulterior strategy. This evaluation is simple and reliable, and is principally
      based on three scores: the TIMI, the GRACE Score or the PURSUIT. Thanks to this
      stratification, high and medium-risk patients are able to benefit from early
      invasive management (stents and anti-GPIIb/IIIa) as recent studies have clearly
      shown. Even if immediate management of patients with non-ST elevation ACS does
      not take account of risk stratification, using such information in the medium and
      long-term does help determine the prognosis. Finally, the risk profile score,
      whatever the score used is today an essential tool, which helps qualify and
      especially compare patients included in international clinical studies.

PMID- 16104614
TI  - [Chronic renal failure: an independent factor of mortality after myocardial
      infarction].
AB  - PURPOSE: The prognostic significance of glomerular filtration rate (GFR) was
      studied in a registry of 754 patients admitted for myocardial infarction in
      Franche Comte; 333 of them had STEMI. PATIENTS AND METHODS: One-year mortality
      was 11.5%: 2.3% in the group with normal GFR, 9.4% in the group with moderate
      renal failure, and 24.2% in the group with severe renal failure. GFR increased
      the prognostic value of conventional risk scores. CONCLUSION: Chronic renal
      failure therefore appears as a major independent predictor of mortality after
      myocardial infarction.

PMID- 16104615
TI  - [Admission and fasting blood glucose are important prognostic markers in acute
      coronary syndromes].
AB  - This paper reviews current evidence on the role of admission and fasting
      glycaemia as prognostic markers in patients with acute coronary syndromes. Though
      both parameters are correlated, they give different prognostic information and
      are related to both in-hospital complications, including death, and long-term
      outcomes. As hyperglycemia at the acute stage of myocardial infarction is an
      independent predictor of untoward cardiovascular events, blood glucose
      measurements should become routine in all patients presenting with acute coronary
      syndromes.

PMID- 16104616
TI  - [Risk stratification in congestive heart failure].
AB  - Congestive heart failure remains a severe condition. Risk stratification is
      necessary to assess the prognosis and discuss the potential timing of heart
      transplant. Numerous criteria have been used, which may be combined to define
      prognostic scores which, however, are rarely used in routine. A few items,
      however, may be used to stratify the risk of mortality and sudden death.

PMID- 16104617
TI  - [Risk assessment before non-cardiac surgery: what do anesthesiologists expect
      from cardiologists?].
AB  - Patients with a cardiac pathology are at high risk of perioperative cardiac
      complications. Therefore, an evaluation of the cardiac risk before a non-cardiac
      surgery has to be performed. The importance of the risk depends on the type of
      surgery, the patient's clinical symptoms and his adaptation to a physical effort.
      Exams are chosen according to the pathology, the information searched for and
      should be non invasive. After the evaluation, a specific preparation of the
      patient and the institution or an adaptation of cardioprotective medications
      should be discussed. The cardiologic consultation also allows a better management
      of antithrombotic or antiplatelet therapy. Preoperative evaluation of the cardiac
      risk is based on the collaboration between cardiologist and anesthesiologist to
      select the patients to evaluate, optimize their management, and decrease the risk
      of complications.

PMID- 16104618
TI  - [Evolution of secondary prevention medication prescriptions after myocardial
      revascularisation: the ANCOR survey].
AB  - The ANCOR survey was designed to assess the evolution of the prescription of
      secondary prevention medications in patients undergoing myocardial
      revascularisation, from the preoperative period to 3-6 months post-procedure. A
      total of 1535 patients (mean age: 64 years, 79% men), 321 after coronary surgery
      and 1214 after percutaneous coronary intervention, were included. Of them 37%
      still described anginal symptoms (Canadian class 1 in 80% of them); 38% still had
      elevated blood pressure (> or = 140 mm HG systolic and/or > or = 90 mmHg
      diastolic) and 27% of previous smokers still smoked after the procedure. All
      classes of secondary prevention medications were more often prescribed after than
      before intervention, antiplatelet agents (63.5 to 89%), beta-blockers (53 to
      73.5%), statins (51 to 3%), ACE inhibitors (27 to 39%) and nicorandil (14 to
      21%). Factors associated with the prescription of the different classes of
      medications were both expected (such as hypertension for ACE inhibitors or
      statins in hyperlipidemic patients) or unsupported by scientific evidence (less
      beta-blockers in diabetic patients). Overall this survey shows that myocardial
      revascularisation constitutes a key point in the management of patients with
      coronary disease, and that cardiologists consider that treatment of the
      atherosclerotic process is as important as the treatment of focal coronary artery
      stenoses.

PMID- 16104619
TI  - [AFFIRM: what we have learned ... and pending issues].
AB  - During these last years, several therapeutic strategies trials have been
      performed in atrial fibrillation: the goal was to compare the rhythm control
      strategy (restoration and maintenance of sinus rhythm) to the rate control
      strategy (slowing of heart rate in atrial fibrillation). The most important of
      these different trials is the AFFIRM study. The main conclusion of this trial is
      that rate control can be chosen in first intention and not only in case of
      failure of the rhythm control strategy. These results can not be applied to 2
      categories of patients: on one hand patients with heart failure and on the other
      hand young patients without cardiopathy in whom the strategy of rhythm control
      and sinus rhythm maintenance, mainly by class I antiarrhythmic drugs, remains the
      better choice.

PMID- 16104620
TI  - [Variable extent of platelet responsiveness to clopidogrel inhibition:
      "clopidogrel resistance"?].
AB  - During percutaneous coronary angioplasty, platelet inhibition by clopidogrel and
      aspirin has drastically decreased the risk of thrombotic occlusion of the stented
      vessels. However, despite the widespread use of these drugs, the incidence of
      acute or subacute stent thrombosis remains elevated, concerning 1 to 2% of the
      treated patients. Considerable differences in the responsiveness to clopidogrel
      could be observed, suggesting a possible underlying biological resistance.
      "Clopidogrel resistance" has recently been associated to an increased risk of
      thrombotic events following coronary angioplasty. Variations in enteric
      absorption, biotransformation in the liver by the CYP3A4, changes in the ADP
      receptor P2Y12, abnomalies of intraplatelet signal transduction, extent of
      platelet activation, class angina, diabetes mellitus may account for the
      considerable interindividual response variability widely reported. In this view,
      laboratory tests evaluating "clopidogrel resistance" might be useful tools for
      the identification and follow-up of patients at higher thrombotic risk. Indeed,
      in these patients, further platelet inhibition can be achieved by higher doses of
      clopidogrel.

PMID- 16104621
TI  - [Drug eluting stents: from evidence based medicine to clinical practice].
AB  - Drug eluting stents have been developed in order to reduce in-stent restenosis
      observed with a 20 to 40% rate in bare-stents. Neoinitimal smooth muscular cells
      proliferation have been characterized as the corner stone of in-stent restenosis.
      Consequently, many anti-mitotic and anti-inflammatory drugs have been evaluated
      in a new stent generation, so called coated stents or drug eluting stents. Three
      major components must be considered to evaluate the beneficial effects: the bare
      stent, the drug, and the deliverance system, most usually a polymer. For the
      present, sirolimus eluting stent and paclitaxel eluting stent are available in
      the market with the european conformity label considering evidence based medicine
      established in randomized trials. Both stents have been shown to reduce in-stent
      restenosis incidence to less than 7%. Long-term follow-up still remain expected
      and would give answers to two safety queries: what is about the incidence of late
      stent thrombosis, what is about mal-apposition consequences in clinical feature.
      Utilization of drug eluting stent in clinical practice must considered materials
      with european conformity and must applied French society of cardiology guidelines
      restricting implantation to patients who meet high-risk restenosis criteria.
      Medicoeconomic approach must be considered beneficial at the present only in
      patients with high restenosis risk. Long-term antiplatelet regimen of aspirin and
      clopidogrel must be considered to avoid late stent thrombosis.

PMID- 16104622
TI  - [Acute myocardial infarction complicating primary antiphospholipid syndrome after
      aspirin and steroids withdrawal].
AB  - A 24-year-old woman, with known antiphospholid antibodies (APS), presented with
      an acute myocardial infarction (AMI) that occurred three months after delivery.
      No risk factors for arteriosclerosis and no past history of arterial/venous
      thrombosis were noted. During pregnancy, aspirin prophylaxis was prescribed and
      followed by steroids after caesarian section. Steroids withdrawal was followed by
      AMI. Immediate coronary angiography revealed thrombotic occlusion of the left
      descending coronary artery; PTCA was successfully performed. She was discharged
      with an antiplatelet and anticoagulant regimen. No recurrent coronary event
      occurred during follow-up.

PMID- 16104623
TI  - [Reversible cardiogenic shock under 5-fluorouracil treatment].
AB  - 5-fluorouracil, an antimetabolite agent, has been widely used since 1957 for
      treatment of varied types of cancer such as gastro-intestinal, pancreas, breast,
      lung, head and neck malignancies. Cardiotoxicity of 5-fluorouracil is rare and
      was first described in 1975. It can induce severe complications and involve vital
      prognosis in the short-term. These complications are less known by cardiologists
      than medical oncologists. The following clinical case represents a potentially
      serious and rare case of completely reversible cardiogenic shock in a patient
      with a colo-rectal cancer. A better knowledge of these complications could reduce
      cases of death by an earlier diagnosis, and a better evaluation of patients with
      high cardiotoxicity risk.

PMID- 16104624
TI  - [Atypical venous thrombosis and protein S deficiency: report of a case].
AB  - A 29 year old man is admitted for hypovemic shock and abdominal pain. This
      critical condition was due to a diffuse mesenteric venous thrombosis and
      intestinal infarction. Five meters of small bowel are resected. Few days later a
      superficial brachial venous thromboembolism grows to superior cava venous and
      bilateral pulmonary embolism. A plasmatic protein S level was 17%. This
      deficiency is considered to be the support of these atypical extended and
      repetitive venous thromboembolism. With an optimal nutrition and long oral
      anticoagulation this patient is alive 17 months after his admission.

PMID- 16104625
TI  - Where should infection control programs for tuberculosis begin?

PMID- 16104626
TI  - Pulmonary complications of HIV-1 infection among adults living in Sub-Saharan
      Africa.
AB  - Sub-Saharan Africa, which has just over 10% of the world's population, is home to
      more than 25 million people living with HIV/AIDS-two thirds of the global total.
      Opportunistic pulmonary infections are major causes of morbidity and mortality
      among HIV-infected adults in the subcontinent. Of these diseases, tuberculosis
      (TB) is by far the most prevalent and serious, and in some countries it causes
      one third or more of all AIDS-related deaths. Because it is so frequent and a
      major public health problem, TB tops the list of differential diagnoses of people
      with or without coexisting HIV infection-who present to the health care system
      with chronic cough and other pulmonary symptoms. As HIV-induced immunosuppression
      worsens, the clinical and radiographic manifestations of TB become increasingly
      atypical. Second among HIV/AIDS-associated pulmonary complications is community
      acquired pneumonia, most commonly caused by Streptococcus pneumoniae, which
      usually responds to standard beta-lactam antimicrobial agents. The prevalence of
      Pneumocystis jirovecii pneumonia is increasing, due to both improved recognition
      of its characteristic clinical and radiographic features and aggressive
      diagnostic interventions. Treatment outcome in most countries, however, has been
      poor. Combined infections, usually including TB, are common. Pulmonary
      nocardiosis, cryptococcosis, Kaposi's sarcoma, and (possibly) histoplasmosis
      appear to be infrequent, but probably underdiagnosed. Improved diagnosis,
      treatment, and prevention of all these diseases are urgently needed, but a
      greatly expanded antiretroviral treatment program will help most of all.

PMID- 16104627
TI  - Assessing the child with cough or difficult breathing.
AB  - In most low-income countries, clinical assessment is the only tool available to
      distinguish an upper respiratory infection (cough or cold) from pneumonia
      requiring antibiotics. The severity of the pneumonia, determined from the
      clinical signs, will determine which patients require more potent antibiotic
      regimens and supplementary oxygen. Careful assessment of the respiratory rate,
      chest in-drawing, ability to feed normally, cyanosis and level of consciousness
      are used to make the diagnosis of pneumonia and determine the severity. Co-morbid
      disease such as malnutrition, measles, HIV infection and malaria increase
      mortality due to pneumonia, and signs of these diseases must be looked for so
      that appropriate treatment can be started. This article carefully describes the
      signs that should be looked for in children presenting with a cough or difficult
      breathing to any health care worker.

PMID- 16104628
TI  - Latent tuberculosis infection among undergraduate medical students in Rio de
      Janeiro State, Brazil.
AB  - SETTING: Five medical schools in three cities with different tuberculosis (TB)
      incidence rates in Rio de Janeiro State, Brazil. OBJECTIVE: To estimate
      prevalence of and associated factors for latent tuberculosis infection (LTBI)
      among medical students. DESIGN: A cross-sectional survey was conducted among
      undergraduate students in pre-clinical, early and late clinical years from
      schools in cities with low (28/100,000), intermediate (63/100,000) and high
      (114/100,000) TB incidence rates. Information on socio-demographic profile,
      previous BCG vaccination, potential TB exposure, co-morbidity and use of
      respiratory protective masks was obtained. A tuberculin skin test (TST) was
      performed using the Mantoux technique by an experienced professional. A positive
      TST, defined as induration > or = 10 mm, was considered LTBI. RESULTS: LTBI
      prevalence was 6.9% (95%CI 5.4-8.6). In multivariate analysis, male sex (adjusted
      odds ratio [aOR] 1.8; 95% CI 1.1-3.0), late clinical years (aOR 1.9; 95% CI 1.01
      3.5), intermediate TB incidence (aOR 4.3; 95% CI 1.3-14.6) and high TB incidence
      in the city of medical school (aOR 5.1; 95% CI 1.6-16.8) were significantly
      associated with LTBI. CONCLUSIONS: The higher prevalence of LTBI in late clinical
      years suggests that medical students are at increased risk for nosocomial
      Mycobacterium tuberculosis infection. The implementation of a TB control program
      may be necessary in medical schools, particularly in cities with higher TB
      incidence.

PMID- 16104629
TI  - Investigation of patient contacts of heath care workers with infectious
      tuberculosis: 6 cases in the Paris area.
AB  - SETTING: From June to October 2003, six cases of infectious tuberculosis were
      reported in health care workers (HCWs) working in hospitals in the Paris area.
      OBJECTIVE: To describe a method of investigation to identify tuberculosis
      infection in patient contacts. DESIGN: To define the cohort of patient contacts,
      the risk of contamination was evaluated based on 1) the degree of infectiousness
      of the HCW, 2) patient characteristics, and 3) the proximity and length of
      exposure. RESULTS: The number of patient contacts selected was very variable. A
      small proportion was investigated in consultation, except for a paediatric
      service in which 43 patient contacts were identified and where the information
      was managed within the service. In this cohort, two patient contacts presented
      tuberculous infection with an unclear link with the infectious HCW. In adults,
      the analysis of the information gathered was difficult due to the different
      screening practices used. CONCLUSION: These results show the importance of better
      targeting screening of patient contacts and of improving the detection of
      tuberculosis cases among HCWs.

PMID- 16104630
TI  - Comparison of erythema and induration as results of tuberculin tests.
AB  - SETTING: Schoolchildren, tuberculosis (TB) patients, and hospital employees in
      Tokyo, Japan. OBJECTIVE: To compare erythema and induration resulting from
      tuberculin tests among TB patients, normal children, and hospital employees with
      and without evidence of atopy. DESIGN: The distributions of diameters of erythema
      and induration were compared among three groups: 951 TB patients, 6139 first
      grade and 6185 seventh-grade children, and 97 volunteer employees classified as
      atopic or non-atopic on the basis of skin tests and serum immunoglobulin E (IgE)
      concentrations. RESULTS: Erythema and induration were highly correlated. The
      distribution of erythema diameters was unimodal, and the distribution of
      induration diameters was bimodal. Erythema was considerably greater than
      induration among persons classified as being atopic. CONCLUSION: Both erythema
      and induration appear to be adequate indices of tuberculin sensitivity. However,
      because most of the world uses induration as the index and virtually all studies
      of tuberculin sensitivity rely on induration, there are advantages in the use of
      induration. It would be desirable to initiate a large prospective study to see
      whether erythema or induration is the better predictor of subsequent tuberculous
      disease, and to confirm our finding that erythema is more likely to be confounded
      by atopy than induration.

PMID- 16104631
TI  - Tuberculosis surveillance among new immigrants in Montreal.
AB  - SETTING: Foreign-born persons account for over 60% of Canadian tuberculosis (TB)
      incidence; immigrants with TB-related lung scarring ('inactive TB') are at
      particularly high risk, and represent an important target for preventive efforts.
      OBJECTIVE: To document the performance of the immigrant surveillance programme
      for inactive TB in Montreal. DESIGN: All immigrants arriving with inactive TB are
      referred by the public health department to the Montreal Chest Institute. We
      prospectively recorded clinical and radiographic data for those evaluated in 1999
      and 2000. We examined physicians' adherence to Canadian guidelines. We also
      evaluated concordance of chest radiographic interpretation. RESULTS: Of 1444
      immigrants notified, 792 (55%) were sent referral letters. Most of the others
      lacked valid addresses. Of the 654 (45%) who were examined, 322 (22%) were
      diagnosed with untreated latent TB, 215 (15%) were recommended therapy, and 156
      (11%) completed it. Of 388 potential candidates for treatment of latent TB, 274
      (71%) underwent tuberculin tests. Treatment decisions followed guidelines for 87%
      of patients with full testing. Agreement between clinicians and chest
      radiologists as to TB-related radiographic abnormalities was frequent (K 0.63).
      Six 'high volume' clinicians performed better than others with respect to
      management and radiographic interpretation. CONCLUSION: Centralised post
      immigration surveillance requires more accurate referrals, and more consistent
      provider performance.

PMID- 16104632
TI  - Chest radiography and tuberculosis case-finding in asymptomatic native and
      immigrant populations in Greece.
AB  - SETTING: A university hospital in southern Greece. OBJECTIVE: To determine the
      prevalence of tuberculosis (TB) and other clinically significant conditions in
      routine chest X-rays (CXRs) of asymptomatic Greeks and immigrants in Greece.
      DESIGN: Prospective study. METHODS: CXRs of 4338 asymptomatic persons (56.8%
      Greeks, 43.2% immigrants, 18-74 years of age) were examined by two experienced
      chest radiologists blinded to identifying data. Abnormalities were recorded and
      the final radiological diagnosis was established by consensus. Results were
      statistically analysed. RESULTS: The majority (94.7%) of the CXRs were reported
      as normal. Clinically significant findings were reported in four cases (0.08%).
      No case of active TB was depicted. The incidence of old TB was higher in the
      Greek-born group than among the immigrants, although the difference was not
      statistically significant. CONCLUSION: The low prevalence of TB in the Greek-born
      group implies that radiographic screening in that group presents an unnecessary
      risk and should possibly be abandoned. Our study does not confirm noticeably
      higher rates of TB in immigrants in comparison to the native Greek population.
      However, larger prospective studies are required to confirm this finding.

PMID- 16104633
TI  - Improved tuberculosis case detection through public-private partnership and
      laboratory-based surveillance, Kannur District, Kerala, India, 2001-2002.
AB  - BACKGROUND: Efforts to intensify global tuberculosis (TB) control are limited by
      difficulties in coordinating with private doctors. More than half of Indian TB
      patients may initially consult a private provider, but many are neither diagnosed
      accurately nor treated effectively. We established and evaluated a public-private
      partnership based on surveillance of TB detected in private laboratories and use
      of standardised directly observed treatment regimens. METHODS: In one district,
      the governmental TB control programme offered training in microscopy to all large
      private sector laboratories, and educated private physicians on the importance of
      microscopy for TB diagnosis. We reviewed records from participating private
      laboratories and all publicly diagnosed patients. RESULTS: Of 2328 pulmonary TB
      patients registered from July 2001 to December 2002, 404 (17%) were detected in
      the private sector. The annual new AFB-positive case notification rate increased
      by 21%, from 27.8/100,000 in 2000 to 33.5/100,000 in 2002. Surveillance at
      private laboratories found an additional 260 nonregistered AFB-positive patients.
      CONCLUSIONS: This public-private partnership substantially increased TB case
      detection and established a sustainable framework for private sector involvement
      in TB control. In the setting of a strong public sector programme, the
      combination of active surveillance of private laboratories along with physician
      sensitisation is a promising approach to improve TB case detection.

PMID- 16104634
TI  - Cost-effectiveness of polymerase chain reaction versus Ziehl-Neelsen smear
      microscopy for diagnosis of tuberculosis in Kenya.
AB  - BACKGROUND: Laboratory services, particularly in large sub-Saharan cities, are
      overstretched, and it is becoming difficult both for patients and health staff to
      adhere to the diagnostic procedures for tuberculosis. Alternative techniques
      would be welcome. The polymerase chain reaction (PCR) has the potential to be
      cost-effective. We compared the cost-effectiveness of two diagnostic strategies,
      Ziehl-Neelsen (ZN) on three specimens followed by chest X-ray (CXR), and AMPLICOR
      MTB PCR on the first specimen only. METHODS: Three sputum samples were collected
      from tuberculosis (TB) suspects attending the Rhodes Chest Clinic, Nairobi. All
      samples were subjected to ZN, PCR and Lowenstein-Jensen culture used as gold
      standard. CXR was used to diagnose smear-negative TB. Cost analysis included
      health service and patient costs. RESULTS: Costs per correctly diagnosed case
      were US dollar 41 and dollar 67 for ZN and PCR, respectively. When treatment
      costs were included, including treatment of culture-negative cases, PCR was more
      cost-effective: dollar 382 vs. dollar 412. CONCLUSION: PCR may be an alternative
      in settings with many patients. PCR is patient friendly, CXR is not necessary
      and, unlike ZN, its performance is hardly affected by the human immunodeficiency
      virus. PCR can handle large numbers of specimens, with results becoming available
      on the same day.

PMID- 16104635
TI  - DOT and timely treatment completion among Asian-born immigrant tuberculosis
      patients.
AB  - SETTING: A large urban tuberculosis (TB) control program. OBJECTIVES: To identify
      factors associated with directly observed therapy (DOT) participation and to
      quantify how early use of DOT affected treatment duration. DESIGN: A
      retrospective study of 731 Asian-born patients with drug-susceptible
      Mycobacterium tuberculosis isolates who were verified in New York City between
      1993 and 1997 and completed treatment. RESULTS: Overall, 297 (41%) of 731
      patients in the study participated in DOT for some or all of their TB treatment.
      DOT participation was significantly associated with TB disease in a pulmonary
      site (adjusted odds ratio [aOR] 2.85, 95% CI 1.86-4.35), more recent year of
      diagnosis (aOR 1.70, 95% CI 1.50-1.94) and male sex (aOR 1.86, 95% CI 1.30-2.66).
      Patients who received > or = 70% of their TB treatment at a health department
      chest clinic were also significantly more likely to participate in DOT (aOR 3.83,
      95% CI 2.55-5.74). Among 297 DOT patients, those who completed treatment by 9
      months received a greater amount of treatment by DOT during the first 4 months of
      treatment than those who took longer to complete treatment. CONCLUSION: Earlier
      DOT participation can lead to overall shorter treatment duration. Health care
      providers should encourage TB patients to participate in DOT as early as possible
      in their TB treatment.

PMID- 16104636
TI  - A 6-month regimen for EPTB with intermittent treatment in the continuation phase:
      a study of 679 cases.
AB  - BACKGROUND: No large studies have demonstrated the effectiveness of a 6-month
      regimen for all forms of extra-pulmonary tuberculosis (EPTB). METHODS:
      Retrospective, observational analysis to evaluate the effectiveness of a 6-month
      treatment regimen (2HRZE/4H3R3) for all patients diagnosed with EPTB in Caracas,
      Venezuela, from 1 January 1998 to 31 December 2000, using direct observation.
      RESULTS: Of 679 patients enrolled, 101 (14.9%) had AIDS. In 83.2% the diagnosis
      was based on microbiological, histological or genetic amplification information.
      Of 612 (90.1%) patients who took more than 90% of the doses, treatment had to be
      altered in six (1%) due to drug side effects. Of the remaining 606 patients who
      took more than 90% of the doses, 603 (99.5%) were cured and three failed. In the
      follow-up conducted 2 years after the end of treatment, only 6 relapsed (1%).
      Cures without relapse were achieved in 24 cases of central nervous system
      involvement, 27 cases of osteoarticular involvement and in the 42 who had miliary
      and/or disseminated TB. CONCLUSION: A 6-month treatment regimen for all forms of
      EPTB, with treatment three times a week during the continuation phase, was highly
      effective.

PMID- 16104637
TI  - Anti-tuberculosis drug resistance in patients with HIV and tuberculosis in South
      India.
AB  - SETTING: Tuberculosis Research Centre clinics at Chennai and Madurai, Tamil Nadu,
      South India. OBJECTIVES: To investigate the prevalence and pattern of drug
      resistance among patients with HIV and pulmonary tuberculosis (PTB). DESIGN:
      Prospective cohort study of HIV-positive patients with PTB between January 2001
      and May 2003. Sputum mycobacterial culture and drug susceptibility testing were
      performed. RESULTS: A total of 204 patients with positive sputum cultures for
      Mycobacterium tuberculosis were included; 167 of them were new cases, and 37 had
      a history of previous anti-tuberculosis treatment for > 1 month. Among the
      former, resistance to isoniazid (INH) was observed in 22 (13%) and MDR-TB in 7
      (4.2%). Reported resistance rates in this geographic area among new cases ranged
      from 15% to 28% for INH and 2.8% to 3.4% for MDR (INH + rifampicin [RMP]). In
      contrast, among HIV-positive patients with a history of previous treatment,
      resistance was found to INH in 10 (27%) and to RMP in 7 (18.9%), while MDR-TB was
      seen in 5 (13.5%) patients. CONCLUSION: Among new TB patients, MDR-TB is
      marginally higher in HIV-positive patients than in the non-HIV-infected
      population in this region. Standard treatment guidelines should be followed.
      Higher rates of drug resistance are observed among previously treated patients.

PMID- 16104639
TI  - Morphological variability and cell-wall deficiency in Mycobacterium tuberculosis
      'heteroresistant' strains.
AB  - SETTING: Sofia State Hospital for Tuberculosis Treatment, Bulgaria. OBJECTIVE: To
      investigate the morphology of two 'heteroresistant' clinical isolates and one non
      heteroresistant isolate, all isolated from newly diagnosed tuberculosis (TB)
      patients, as well as the reference strain H37Rv. Heteroresistant isolates
      contained clonally-related sensitive and drug-resistant organisms which could
      subsequently be separated using drug-containing primary cultures and had been
      isolated from patients originally diagnosed with susceptible TB by the 1%
      proportion method. Mycobacterial cultures were evaluated by transmission electron
      microscopy after 25 days of cultivation in Dubos broth. RESULTS: In contrast to
      H37Rv and the non-heteroresistant isolate, the bacterial populations in both
      heteroresistant isolates demonstrated distinct pleomorphic variability and
      coexistence of both classical and cell-wall deficient forms. Electron micrographs
      of mutants resistant to streptomycin and isoniazid showed predominance of
      atypical granular L-forms, which formed L-type colonies on Dubos agar.
      CONCLUSION: The L-form transformation processes, observed both in clinical
      heteroresistant isolates containing mixed populations of Mycobacterium
      tuberculosis organisms with different resistance gene genotypes and in the
      isolated resistant (mutant) clones, indicate a possible link between resistance
      and cell-wall deficient L-phase states and suggest one of the possible mechanisms
      by which resistant mutants are able to survive in vivo.

PMID- 16104638
TI  - Multicenter study of MTT and resazurin assays for testing susceptibility to first
      line anti-tuberculosis drugs.
AB  - OBJECTIVE: A multicentre evaluation was performed to assess two rapid low-cost
      methods, MTT (3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide) and
      resazurin assays, for testing the susceptibility of Mycobacterium tuberculosis to
      the first-line anti-tuberculosis drugs rifampicin (RMP), isoniazid (INH),
      ethambutol (EMB) and streptomycin (SM). METHODS: Thirty coded M. tuberculosis
      strains were sent to seven laboratories located in Latin America, representing
      six countries. Each site performed the colorimetric assays, MTT and resazurin,
      blind for the first-line drugs RMP, INH, EMB and SM. The minimum inhibitory
      concentration results obtained were compared to the conventional proportion
      method on Lowenstein-Jensen medium. RESULTS: After establishing the breakpoint
      concentrations, excellent results were obtained for RMP, INH and EMB, with levels
      of specificity and sensitivity of between 96% and 99%. CONCLUSION: MTT and
      resazurin assays are promising, accessible new alternative methods for middle-
      and low-resource countries that need low-cost methods to perform rapid
      susceptibility testing of M. tuberculosis to key anti-tuberculosis drugs.

PMID- 16104640
TI  - Detection of free and immune-complexed serine protease and its antibody in TB
      patients with and without HIV co-infection.
AB  - OBJECTIVE: To understand the usefulness of detecting tuberculous IgG antibodies
      against mycobacterial excretory-secretory 31 kDa serine protease antigen (SEVA TB
      ES-31) and circulating free and circulating immune-complexed (CIC) serine
      protease in TB patients with and without HIV infection. DESIGN: Serum was
      collected from 144 individuals: patients with TB, with TB-HIV co-infection and
      HIV infection only, and ill and healthy controls. SEVA TB ES-31 antigen, a serine
      protease isolated from Mycobacterium tuberculosis H37Ra culture fluid, was used
      in indirect penicillinase ELISA to detect tuberculous antibodies. Similarly,
      affinity purified anti-ES-31 antibody was used in sandwich ELISA to detect
      circulating free and CIC serine protease. RESULTS: There was less sensitivity for
      tuberculous antibody in HIV-infected TB patients (46%) than in those with TB
      alone (87%) using mycobacterial serine protease. However, the sensitivity of
      detection of TB in the presence of HIV increased to 87% by concomitant detection
      of circulating free and CIC serine protease antigen. CONCLUSION: Detection of
      free and CIC tuberculous serine protease antigen along with antibody is more
      useful for detecting TB in the presence of HIV co-infection.

PMID- 16104641
TI  - Tuberculous mastitis: a disease not to be forgotten.
AB  - OBJECTIVE: To present our experience with tuberculous mastitis to increase the
      awareness of surgeons, pathologists and radiologists about this rare disease.
      PATIENTS AND METHODS: Records of nine patients with tuberculous mastitis were
      retrospectively reviewed. RESULTS: Tuberculous mastitis was seen in 0.6% of our
      patients with surgically treated mammary disease. There were eight females (mean
      age 32.9 years) and one male. All female patients were parous, two were lactating
      and one was pregnant. A unilateral breast mass mimicking breast cancer and breast
      abscess were the presenting feature in seven and two patients, respectively. Two
      patients had previous pulmonary tuberculosis. Radiological findings were not
      specific. Fine needle aspiration was performed for seven patients, and excisional
      biopsy for all patients. The final diagnosis was based on demonstration of acid
      fast bacilli in biopsy specimens in two patients, and histopathology aided by
      polymerase chain reaction in the remaining seven patients. Mastectomy was
      performed for one patient due to severe breast destruction. All patients had
      satisfactory results on antituberculosis treatment. CONCLUSION: Tuberculous
      mastitis is a rare entity in patients with mammary disease. A high index of
      suspicion is the cornerstone for diagnosis. Conservative surgery and anti
      tuberculosis drugs seem to be adequate treatment.

PMID- 16104642
TI  - Incidence of GOLD-defined chronic obstructive pulmonary disease in a general
      adult population.
AB  - SETTING: The incidence of chronic obstructive pulmonary disease (COPD) as defined
      by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has not
      previously been examined. OBJECTIVE: To estimate cumulative 9-year GOLD-defined
      COPD incidence in a general adult Norwegian population, to analyse sex, age,
      smoking habits and residential area as predictors, and to assess the level of
      underdiagnosis. DESIGN: Based on a random stratified population sample examined
      in 1987-1988, 908 adults (71%) participated in a follow-up examination in 1996
      1997. Associations between risk factors and COPD incidence were examined with
      logistic regression analyses. RESULTS: The cumulative incidence of COPD among
      persons at risk in 1987-1988 was 6.1% (95% confidence interval [CI] 4.0-8.1).
      Adjusted odds ratios (OR) for current smokers and ex-smokers were 9.6 (95% CI 3.6
      25.2) and 5.0 (95% CI 1.8-13.8), compared to never smokers. Risk for COPD
      incidence further increased with pack years. Subjects aged 45-74 had an OR of 9.8
      (95% CI 4.3-22.5) relative to those aged 18-44. Sex and residential area were not
      significantly associated with COPD incidence. Only 43% of the incident cases had
      physician-diagnosed asthma, bronchitis, emphysema and/or COPD. CONCLUSION:
      Approximately 6% developed COPD over 9 years. Smoking and aging were important
      incidence predictors. Our study suggests a substantial underdiagnosis of COPD
      among adults in this community.

PMID- 16104643
TI  - Comparison of scanty AFB smears against culture in an area with high HIV
      prevalence.
AB  - To verify among tuberculosis (TB) suspects attending hospitals in Abuja, Nigeria,
      if sputum smears graded as scanty are false-positive, sputum smears from 1068
      patients were graded with the International Union Against Tuberculosis and Lung
      Disease classification. One specimen was cultured. Eight hundred and twenty-four
      (26%) smears were positive, 137 (4%) scanty and 2243 negative. Of 1068 cultures,
      680 (64%) were positive. One hundred and thirty (95%) scanty and 809 (98%)
      positive smears were culture-positive. Twelve of 18 patients with a single scanty
      smear and 51 of 52 with > or = 2 scanty smears were culture-positive. Fewer than
      < 5% scanty results, < 1% of the patients treated for TB, are false-positive.

PMID- 16104644
TI  - Mutations in the rpoB gene of rifampicin-resistant Mycobacterium tuberculosis
      clinical isolates from Lithuania.
AB  - A total of 196 rifampicin (RMP) resistant Mycobacterium tuberculosis isolates
      were searched for mutations in the cluster I region of the rpoB gene. Seventeen
      different types of mutations were observed in 184 (93.9%) isolates. The remaining
      isolates searched also had no mutations in the N-terminal region of this gene.
      Mutations were most frequently detected at single codons Ser531 (47.4%), His526
      (20.9%), and Asp516 (20.4%). Our data indicate that genotypic drug susceptibility
      assays based on detection of mutations at the specific codons of the rpoB gene
      should be effective for predicting resistance to RMP and rifabutin and multidrug
      resistance in Lithuania.

PMID- 16104645
TI  - Microplate nitrate reductase assay versus Alamar Blue assay for MIC determination
      of Mycobacterium tuberculosis.
AB  - A rapid colorimetric, microplate based nitrate reductase assay (NRA) method for
      minimum inhibitory concentration (MIC) determination of clinical isolates of
      Mycobacterium tuberculosis was compared with the microplate Alamar Blue assay
      (MABA), presently in vogue. Reproducible results were obtained in 7 days by NRA.
      The NRA method was found to be inexpensive, suitable for MIC determination
      against M. tuberculosis and can be suggested as an ideal substitute to MABA.

PMID- 16104646
TI  - Iron overload and tuberculosis: a case for iron chelation therapy.

PMID- 16104647
TI  - Malpractice claims payments decreased, yet premiums soared.

PMID- 16104648
TI  - Primary cause of high U.S. costs? High U.S. prices.

PMID- 16104649
TI  - Misoprostol and women's health in Africa.

PMID- 16104650
TI  - Management of breech presentation in areas with high prevalence of HIV infection.

PMID- 16104651
TI  - Contraceptive implants.
AB  - In response to the need of some women for long-acting, effective and safe
      contraceptives, the scientific community developed non-biodegradable
      progestational subdermal implants that act by making the cervical mucus viscous,
      with ovulation inhibition and thinning of the endometrial lining. The
      contraceptive protection is within 24 hours and the cumulative failure rate is
      low. Contraceptive implants require little or no motivation following adequate
      counselling. In current use are multirod implants (Norplant I and Norplant II
      Jadelle) and single rod implant (Implanon and Uniplant). Although menstrual
      symptoms associated with progestational regimens are the major compliance and
      acceptability factors within the first year of use, menstrual disturbance
      generally improves. Continuation rates for implant use are high among those who
      have had adequate pre-insertion counselling because the perceived advantages
      greatly outweigh the nuisance effects. Other side effects of implants are similar
      to those observed with hormonal pills--headache, weight changes, mood swings and
      abdominal bloating. Training of physicians and nurses in the art of insertion and
      removal techniques is a pre-requisite for a successful implant programme. This
      should also be backed by integration of implants into the national commodity
      logistics systems to ensure adequate local budgetary provision for contraceptive
      implant procurement rather than reliance on donor supply.

PMID- 16104652
TI  - Effect of uniplant on liver function in Egyptian women with asymptomatic
      hepatitis B virus infection.
AB  - Uniplant is a single 35mm contraceptive implant releasing nomegestrol acetate
      with an effective life span of one year. This study was undertaken to evaluate
      the possible effects of three-year use of uniplant on some liver enzymes (SGPT,
      SGOT and GGT) in Egyptian women and to evaluate whether the past asymptomatic
      hepatitis B virus infection would predispose to any changes in these enzymes.
      This is an uncontrolled prospective study including 187 women of reproductive age
      who desired contraception for three years (three segments each year). They were
      apparently healthy on clinical assessment with no history of jaundice or liver
      diseases. They also had normal levels of liver function enzymes (SGPT, SGOT &
      GGT). Fasting blood samples were drawn at admission for assessing the levels of
      these liver enzymes and to detect anti-HBS antibodies as a marker of past
      asymptomatic hepatitis B virus infection (HBV) and HBS antigen to diagnose the
      chronic carrier state. The liver enzymes were measured at 6th. 12th, 18th, 24th,
      30th and 36th month of use, and 3-6 months after implant removal. Out of 187
      subjects enrolled 159, 83 and 33 women completed one, two and three years of
      Uniplant use respectively. The mean levels of SGPT, SGOT and GGT showed slight
      but significant elevations at the end of the first and second years of use
      compared to the pre-insertion levels. By the end of the third year, the elevated
      mean values of all enzymes gradually decreased to approach the pre-insertion
      levels without any significant differences. The percentage of anti-HBS antibodies
      positive titre due to past asymptomatic infection was 23.3% (n = 41) while HBsAg
      positive antigenaemia (i.e., carrier state) was 3.4%, (n = 5). In both groups of
      women--anti-HBS antibodies positive (n = 41) without antigenaemia and anti-HBS
      antibodies negative (n = 129)--the changes in the mean levels of all enzymes
      during uniplant use were closely similar without any statistical significance.
      These results demonstrated that: (1) uniplant induced slight but significant
      elevations in the mean levels of SGPT, SGOT and GGT these elevations were within
      the normal ranges, completely reversible and of doubtful clinical significance.
      (2) The non-carrier women who had been exposed to past asymptomatic HBV infection
      showed no significant effects on the studied liver enzymes compared to the normal
      women during long-term use of Uniplant.

PMID- 16104653
TI  - Hearing native voices: contraceptive use in Matemwe Village, East Africa.
AB  - Although fertility declines have been documented in various parts of Africa,
      fertility rates remain high in Tanzania. Widespread resistance to modern
      contraception is one factor associated with high fertility in Tanzania. The aim
      of this study was to identify cultural barriers to modem contraceptive use in
      Matemwe village, Zanzibar. In May 2003, more than 50 in-depth interviews were
      conducted with community leaders, health care workers and couples in Matemwe.
      Despite free and easy access to contraceptives, only 2% of Matemwe women
      participated in the village's family planning programme. Several factors were
      found to influence contraceptive use, including strong Muslim beliefs, male
      dominance over females (especially in polygynous relationships), and limited
      exposure to modern ideas via education and travel. Interviews indicated that in
      order to lower fertility in Matemwe, cultural barriers to family planning must be
      confronted. Successful implementation of a family planning programme hinges on
      the ability of policymakers to integrate modern ideas about contraception with
      Matemwe's traditional religious and political culture.

PMID- 16104654
TI  - STI/HIV co-infections in UCH, Ibadan, Nigeria.
AB  - Sexually transmitted infections (STIs) are poorly recognised and inadequately
      treated in Nigeria in spite of the fact that it constitutes a major risk for HIV
      transmission. This study was carried out to ascertain STI/HIV co-infection rate
      and to obtain relevant socio-demographic and reproductive health data associated
      with STIs. This information is urgently needed for designing STI/HIV control
      strategies. All consenting patients with history suggestive of STI, who attended
      STI clinic at the University College Hospital, Ibadan, between March and November
      2001 were enrolled in the study. Of the 210 patients seen, 98 (46.7%) were males
      while 112 (53.3%) were females (p > 0.05). One hundred and fifty six (74.3%) of
      them were aged 20-39 years while only 10 (5.1%) were adolescents. Twenty (9.5%)
      had laboratory diagnosis of STIs, out of which 6 (30%) were also HIV positive.
      Among those with STIs, 8 (40%) had gonorrhoea, 8 (40%) had candidiasis, while 4
      (25%) were positive for Trichomonas vaginalis. None of the patients' sera was
      positive for Treponema palladium antibody HIV prevalence rate in the study was
      21.9%. Highest rate was found in patients aged 20-29 years while no adolescent
      and no one over 50 years old was HIV positive. Five (62.5%) of the patients with
      gonorrhoea were also HIV positive, a lower percentage (25%) of those with
      trichomoniasis were positive for HIV, while none of those infected with
      candidiasis was HIV positive. STI/HIV co-infection rate was 30%. This study
      reveals a high STI/HIV co-infection rate, indicating that there is a need for
      proper management of STIs as a way of reducing the spread of HIV infection in
      Nigeria.

PMID- 16104655
TI  - Parental factors and sexual risk-taking among young people in Cote d'Ivoire.
AB  - Cote d'Ivoire is the country worst affected by the HIV epidemic in West Africa,
      and young people in this country are a particularly vulnerable group. This study
      examined the relation between parental factors and sexual risk-taking among young
      people using logistic regression and survival analysis methods. Three parental
      factors (living in the same household as the father during childhood, perceived
      parental disapproval of early and premarital pregnancy, and parent-child
      communication about sexual abstinence) were positively associated with primary
      sexual abstinence (defined as yet to experience sexual debut), secondary sexual
      abstinence (defined as sexual abstinence subsequent to sexual debut) and reduced
      number of sex partners. The findings suggest that parental monitoring and control
      are important predictors of youth sexual behaviours and underscore the need to
      target parents and guardians in efforts to promote responsible sexual behaviours
      among adolescents. It is important to promote parent-child communication about
      sexual issues and empower parents and guardians to communicate effectively with
      their children and wards about sexual issues.

PMID- 16104656
TI  - Perceived sufficiency and usefulness of IEC materials and methods related to
      HIV/AIDS among high school youth in Addis Ababa, Ethiopia.
AB  - This study was conducted to assess the perceived sufficiency and usefulness of
      HIV/AIDS information, education and communication (IEC) messages and materials as
      well as to identify preferences for IEC sources and methods. Data were collected
      using a self-administered questionnaire and focus group discussions. A total of
      901 students in Addis Ababa, Ethiopia, participated in the study. Over three
      quarters of the respondents believed in the usefulness of IEC. IEC materials were
      perceived to be useful in increasing knowledge about HIV/AIDS by 456 (51%), to
      influence attitude by 357 (40%) and to acquire safer sexual practices by 382
      (42%) of the respondents. None of the information sources and messages available
      for high school students highly satisfied the sufficiency indicators. Even though
      no single information source was highly preferred, radio and television ranked
      top. Life skills training was the most desired intervention by the students. IEC
      on HIV/AIDS was able to acquaint students with the disease rather than equipping
      them with knowledge and skill needed in their daily life. Therefore, appropriate
      and mutually reinforcing IEC messages with emphasis on life skill training are
      recommended.

PMID- 16104657
TI  - Sexual behaviour, HIV-related knowledge and condom use by intra-city commercial
      bus drivers and motor park attendants in Lagos, Nigeria.
AB  - A study was undertaken among 395 intra-city commercial bus drivers, conductors
      and motor park attendants in a sub-urban community in Lagos, Nigeria. It was
      aimed at ascertaining the level of knowledge of the participants on sexually
      transmitted diseases including AIDS, their sexual practices and perceived
      vulnerability to these diseases and, in particular, their attitude to and use of
      condoms. A semi-structured interview schedule was used for data collection. The
      men were found to have a strongly woven network of sexual relationships. Their
      sexual network included, apart from their wives and regular partners, commercial
      sex workers, young female hawkers, schoolgirls, and market women within and
      outside the motor parks. More than two thirds (74.3%) of the men had multiple sex
      partners and many of them had had sexually transmitted diseases at one time or
      another. Condom ever-use rate was 65.6% but consistent and regular use rate with
      casual partners was 11.6%. Almost all the respondents (96.4%) knew themselves to
      be at high risk of contracting STDs, while 87.6% felt that it was impossible for
      them to "catch" AIDS. Poor knowledge of risk factors for STDs was exhibited, as
      many of them attributed their previous STDs to excessive exposure to the sun,
      having sex in the sun, and their partners remaining in the bath for too long.
      Intra-city commercial bus operators and men at motor parks are a high risk group
      for acquiring HIV infection. Their sexual networking with a variety of women
      within and outside the parks also seems to suggest that they play a major role in
      transmitting HIV infection in urban communities in Nigeria. There is a need for
      intervention programmes with a focus on men at motor parks and similar high risk
      groups.

PMID- 16104658
TI  - HIV and sexually transmitted infections among women presenting at urban primary
      health care clinics in two cities of sub-Saharan Africa.
AB  - In a cross-sectional study, 786 consenting women from two cities in Africa,
      Harare and Moshi, attending primary health care clinics were interviewed,
      examined and tested for HIV and other sexually transmitted infections (STIs). The
      aim of the study was to assess and compare differences in the characteristics
      that may affect the prevalence of HIV/STIs among women in the two cities.
      Multivariate analysis was used to generate odds ratio. STIs and behaviour
      characteristics among this low risk group of women could not fully explain the
      higher HIV prevalence in Zimbabwe, 29.3% compared to 11.5% in Tanzania (p <
      0.01). Interventions should target identified risk factors with particular
      attention to youths.

PMID- 16104659
TI  - An assessment of the awareness of sexual and reproductive rights among
      adolescents in south western Nigeria.
AB  - This study, conducted in Ikeja and Ikorodu Local Government Areas of Lagos State,
      examined the awareness of sexual and reproductive rights among adolescents in
      south-western Nigeria. A total of 600 in-school and out-of-school adolescents
      were interviewed using quantitative and qualitative methods. The study revealed
      that majority of the adolescents were aware of sexual and reproductive health
      rights (60.3% in Ikeja LGA and 62.3% in Ikorodu LGA) but lacked knowledge of
      contents of the rights. Majority of them in various categories (by school
      condition and type of settlement) were not aware of sexual and reproductive
      health programmes being implemented for adolescents. In addition, those who were
      aware of such intervention programmes could not access or use the services due to
      certain sociocultural barriers. The study recommends formulation of appropriate
      intervention strategies and programmes for adolescents so that they may be aware
      and knowledgeable of their sexual and reproductive rights.

PMID- 16104660
TI  - Recognition of high risk pregnancies and referral practices among traditional
      birth attendants in Mkuranga District, Coast Region, Tanzania.
AB  - A cross-sectional study was carried out in Mkuranga District of Tanzania with the
      aim of comparing the ability of trained and untrained traditional birth
      attendants (TBAs) in identifying women with danger signs for developing
      complications during pregnancy and childbirth as well as their referral
      practices. Study findings revealed that majority of the TBAs (86.5%) had not
      received any training. Trained TBAs were more knowledgeable on danger signs
      during pregnancy and childbirth and were more likely to refer women with
      complications to a health facility, compared to untrained TBAs. The authors
      recommend that in resource constrained countries like Tanzania and especially in
      remote rural areas, TBAs should be trained on early identification of mothers
      with obstetrical complications and on their prompt referral to health facilities
      that can provide emergency obstetric care.

PMID- 16104661
TI  - Abdominal pregnancy at the University College Hospital, Ibadan: a ten-year
      review.
AB  - Fourteen cases of abdominal pregnancy managed at the University College Hospital,
      Ibadan, Nigeria, over a ten-year period (January 1994 to December 2003) were
      reviewed. The incidence ratio of abdominal pregnancy was one in 654 deliveries.
      It accounted for 4.3% of ectopic pregnancies. Age range was 20 to 43 years; 63.4%
      of the patients were unemployed and 50% were nullipara. Pre-operative diagnosis
      was possible only in half of the cases. Only two patients with advanced
      pregnancies and live fetuses (14.3%) were allowed to have conservative management
      while the others had immediate laparotomy. Live birth rate was 7.1%, but overall
      fetal survival rate was 0%. Fetal malformations were common, with talipes
      equinovarus and jaw abnormalities occurring in 49.2% and 14.3% respectively.
      Twelve patients (85.7%) who had complete removal of the placenta, though lost
      more blood, had better outcome than those with placenta left in-situ. The case
      fatality rate was 7.1%.

PMID- 16104662
TI  - Is serum magnesium estimate necessary in patients with eclampsia on magnesium
      sulphate?
AB  - The therapeutic index of magnesium is said to be low, hence, there are fears of
      toxicity when used as anticonvulsant in eclamptic patients. The objective of this
      study was to determine the serum levels of magnesium in eclamptic patients
      treated with magnesium sulphate and relate the levels with clinical indicators.
      It was a prospective study involving consecutive eclamptic patients that were
      managed between January and December 2002, with magnesium sulphate as the sole
      anticonvulsant agent, using a modified Pritchard regimen. Blood samples were
      taken before the administration of the loading and maintenance doses of magnesium
      sulphate and serum levels of magnesium were estimated using the Jenway 605
      colorimeter. There were 19 patients and 72 blood samples. The mean baseline serum
      magnesium was 0.72 +/- 0.10 mmol/L while serum magnesium levels when the patients
      were on treatment ranged from 1.95 to 2.82 mmol/L. No serum magnesium level was
      greater than 3.0 mmol/L and none of the patients had clinical evidence of
      magnesium toxicity. We conclude that serum magnesium levels in these patients
      were within the therapeutic range, therefore, routine estimation of this cation
      is not necessary. Even where the laboratory facility is available, it is
      suggested that serum estimation be limited to cases where clinical monitors
      suggest toxicity.

PMID- 16104663
TI  - Induced abortion in Nigeria: findings from focus group discussion.
AB  - Abortion is carried out daily in Nigeria despite the restrictive abortion law.
      This study was carried out to obtain information on societal attitude to the
      issues of family planning, unwanted pregnancy, abortion, adoption of children and
      laws relating to them. Focus group discussions were held in south-western Nigeria
      among 11 sub-groups. Participants felt that there was high prevalence of unwanted
      pregnancy and abortion particularly among youths. They had high level awareness
      of contraceptives and ascribed its low use to negative side effects, high cost
      and provider bias. Christians favoured planning of pregnancies while the Muslims
      did not. Majority of the respondents had negative perception of induced abortion.
      Some of them supported abortion if the education of the young girl would be
      disrupted, if paternity of pregnancy is in dispute, or if it would save the
      family from shame. Participants supported the enactment of laws that would make
      adoption of unwanted children easier.

PMID- 16104664
TI  - "Abortion? That's for women!" Narratives and experiences of commercial motorbike
      riders in south-western Uganda.
AB  - Although constitutionally illegal, induced abortion is a vital reproductive
      health option in Uganda. This paper analyses men's narratives about meanings of,
      and experiences with, abortion. Men play significant roles in abortion as
      instigators, facilitators, collaborators, transporters, advisors, informers,
      supporters or punishment givers. Many participants were knowledgeable about
      abortion. Attitudes were ambivalent, with initial reactions of denial and
      relegation of abortion to women's private domains. Further exploration, however,
      revealed active support and involvement of men. Interpretations of abortion
      ranged from 'dependable saviour' to 'deceptive sin'. Though a private action,
      abortion is socially scripted and often collectively determined by wider social
      networks of kinsmen, the community, peers, law and religion. A disjuncture exists
      between dominant public health discourse and the reality of local men who
      interact with women and girls as wives, lovers, sex sellers, mothers, daughters
      and sisters. Interventions targeting men about abortion should include safe sex
      education, provide safe abortion services and create stronger social support
      mechanisms. Policy and law should incorporate local knowledge and practice.

PMID- 16104665
TI  - Heterotopic pregnancy with spontaneous vaginal delivery at 36 weeks and
      laparotomy at term--a case report.
AB  - Heterotopic pregnancy, although rare, is occurring more frequently because of an
      increase in genital infection and the escalating use of new reproductive
      technologies in infertility patients. The case of a 30-year-old para 2 + 1
      prophetess is presented. She had a spontaneous vaginal delivery at term.
      Persistent abdominal pain and distension led to suspicion of heterotopic
      pregnancy. This was confirmed by ultrasonography. Laparotomy revealed a macerated
      fetus in the peritoneal cavity The purpose of this report is to sensitise
      practitioners about the reality and existence of the condition.

PMID- 16104666
TI  - Prenatal screening: incorporating the first trimester studies. Proceedings of an
      National Institute of Child Health and Human Development workshop. December 16
      17, 2004.

PMID- 16104667
TI  - First-trimester screening for chromosomal abnormalities.
AB  - There is extensive evidence that effective screening for major chromosomal
      abnormalities can be provided in the first trimester of pregnancy. Randomized
      studies have established that the risk of miscarriage from chorionic villus
      sampling in the first trimester is the same as for amniocentesis in the second
      trimester. Prospective studies have demonstrated that screening by a combination
      of fetal nuchal translucency (NT) and maternal serum free-beta-human chorionic
      gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) can
      identify 90% of fetuses with trisomy 21 and other major chromosomal abnormalities
      for a false-positive rate of 5%. This is superior to the 30% detection rate
      achieved by maternal age and 65% by second-trimester maternal serum biochemistry.
      A further improvement in the effectiveness of first-trimester screening is likely
      to be achieved by a risk-orientated two-stage approach. In this, the patients are
      subdivided into a high-risk group, requiring invasive testing, a low-risk group,
      which can be reassured that an abnormality is unlikely, and an intermediate-risk
      group (risk of 1 in 101 to 1 in 1000), in which further assessment is performed
      by first-trimester ultrasound examination (for presence/absence of the nasal bone
      or presence/absence of tricuspid regurgitation or normal/abnormal Doppler
      velocity waveform in the ductus venosus), and chorionic villus sampling is
      performed if their adjusted risk becomes 1 in 100 or more. As with all aspects of
      good clinical practice, those performing first-trimester scans should be
      appropriately trained and their results subjected to external quality assurance.
      This process was well established by the Fetal Medical Foundation several years
      ago and is widely accepted internationally.

PMID- 16104668
TI  - First-trimester Down syndrome screening: component analytes and timing for
      optimal performance.
AB  - The most effective first-trimester Down syndrome screening protocol in current
      use employs three independent markers: maternal serum levels of PAPP-A and free
      beta hCG, and measurement of fetal nuchal translucency (NT). Eleven weeks appears
      to be the optimum gestational age for performing first trimester DS risk
      assessment. Although the discrimination of free beta hCG improves with increasing
      gestational age and is greatest at 13 weeks, PAPP-A and NT perform optimally at
      10 and 11 weeks, respectively. In addition to accurate pregnancy dating, first
      trimester screening performance is improved by using a consistent NT measurement
      technique, NT cut-offs adjusted for gestational age or crown-rump length, and
      possibly center- or operator-specific NT medians. Whether or not absence or
      presence of the nasal bone adds to screening accuracy is a matter of some debate.
      Finally, because enlarged NT has been associated with cardiac defects and other
      structural anomalies, even in euploid fetuses, its presence should prompt a
      targeted second trimester ultrasound examination.

PMID- 16104669
TI  - Second trimester serum markers.
AB  - Prenatal screening for Down syndrome in the early second trimester with multiple
      maternal serum markers has been available for more than 15 years. The multiple
      marker combination with the highest screening performance currently available is
      alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin
      (hCG), and inhibin A, together with maternal age (so-called quad marker test).
      With this combination, a detection rate of 80% at a 5% false positive rate is
      achieved. Inhibin A, the newest addition to second trimester serum screening, is
      an alpha-beta subunit hormone of placental origin, and is measured using a
      monoclonal two-site ELISA validated for use in prenatal screening. Quality
      control parameters for inhibin A measurement are acceptable and are monitored
      through the proficiency testing program administered by the College of American
      Pathologists. Research into other possible second trimester screening markers has
      included studies on the maternal urine and serum levels of an hCG variant,
      hyperglosylated hCG (h-hCG; invasive trophoblast antigen). Recent data indicate
      that h-hCG is similar to hCG itself, although its measurement in maternal urine
      may improve the performance of the established serum marker combinations. With
      the introduction of first trimester screening markers and their use in an
      integrated first and second trimester marker approach to screening, and with the
      fact that many women do not seek prenatal care until the early second trimester,
      prenatal screening for Down syndrome using second trimester serum markers remains
      a major resource in obstetrical care.

PMID- 16104670
TI  - The mid-trimester genetic sonogram.
AB  - The genetic sonogram is a composite algorithm combining multiple individual
      markers to increase Down syndrome risk prediction. Transformation of sonographic
      information into a standard mathematical format represented an early challenge
      that has now been surmounted. Using increasingly sophisticated mathematical
      techniques, individual patient risk can be estimated. High diagnostic accuracy
      comparable to standard mid-trimester serum algorithms has been reported. Most
      recently, a few studies have reported the ability to combine serum and
      biochemical markers to achieve diagnostic accuracy comparable to first-trimester
      screen. Even fewer studies have reported combinations of ultrasound and maternal
      urine markers. While it is clear that consistently high sensitivity and
      specificity for Down syndrome can be achieved, almost all the studies are based
      on high-risk groups. Studies in low-risk populations have suffered from lack of
      standardization. The relevance of genetic sonogram in a low-risk population thus
      remains to be proven. The most significant challenge, however, remains the
      development of uniform and reproducible sonographic and measurement standards.
      This is likely to be the most important factor in optimizing the accuracy of the
      mid-trimester genetic sonogram.

PMID- 16104671
TI  - Invasive prenatal diagnostic procedures 2005.
AB  - Amniocentesis and Chorionic Villus Sampling have been the two most common
      prenatal diagnostic procedures for decades. There are wide variations in
      utilization, operator skills, quoted procedure risks, actual observed risks, and
      patient choices that come from highly variable counseling as to those risks. The
      compilation of published data suggests procedure risks of amniocentesis to be
      about 1/200 and in very skilled hands to be slightly lower. The risks of CVS in
      very experienced hands may also be about 1/200. Most studies comparing CVS to
      amniocentesis in skilled hands have found equivalency of risks. No well
      controlled studies support claims of amniocentesis risk at 1/1000 or lower. There
      is no increased risks of limb reduction defects following CVS at 10 weeks or
      greater, but there is an increase in Talipes from "Early Amniocentesis." In the
      first trimester CVS is the safer procedure.

PMID- 16104672
TI  - Evaluation of Down syndrome screening strategies.
AB  - Women contemplating pregnancy today have many different Down syndrome screening
      protocols from which to choose. Sensitive and specific first and second trimester
      screening protocols are now widely available, and strategies that combine first
      and second trimester markers are moving from investigational use into the
      clinical arena. Modeling indicates that a high detection rate (85%) associated
      with a very low screen positive rate (1.3%) can be achieved with contingent
      screening, in which all women undergo first trimester screening and only a
      portion (25%) go on to second trimester screening.

PMID- 16104673
TI  - SURUSS in perspective.
AB  - BACKGROUND: Until the publication of the Serum Urine and Ultrasound Screening
      Study (SURUSS) report, it was difficult to compare the different antenatal
      screening tests for Down's Syndrome because of variations in study designs. We
      here present the main results from SURUSS, updated to take account of recent
      information on nuchal translucency in Down's Syndrome pregnancies, and discuss
      their implications. METHODS: SURUSS was a prospective study of 47,053 singleton
      pregnancies (including 101 pregnancies with Down's Syndrome) conducted in 25
      maternity units. Nuchal translucency measurements were taken. Serum and urine
      samples collected between 9 and 13 weeks, and again between 14 and 20 weeks of
      pregnancy were stored. Samples from each affected pregnancy and five matched
      controls were tested for currently used or suggested biochemical Down's Syndrome
      screening markers. Pregnancies were followed up to determine the presence or
      absence of Down's Syndrome. For an 85% Down's Syndrome detection rate, the false
      positive rate for the Integrated test (nuchal translucency and pregnancy
      associated plasma protein-A [PAPP-A] at 11 completed weeks of pregnancy, and
      alpha-fetoprotein, unconjugated oestriol [uE3], free beta or total human
      chorionic gonadotrophin (hCG) and inhibin-A in the early second trimester) was
      0.9%, the Serum integrated test (without nuchal translucency) 2.7%, the Combined
      test (nuchal translucency with free beta-hCG and PAPP-A at 11 weeks) 4.3%, the
      Quadruple test (alpha-fetoprotein, uE3, free beta or total hCG and inhibin-A)
      6.2%, and nuchal translucency at 11 weeks, 15.2%. All tests included maternal
      age. Using the Integrated test at an 85% detection rate, there would be six
      diagnostic procedure-related unaffected fetal losses following amniocentesis per
      100,000 women screened compared with 35 using the Combined test or 45 with the
      Quadruple test. CONCLUSIONS: The Integrated test offers the most effective and
      safe method of screening for women who attend in the first trimester. The next
      best test is the Serum integrated test. The Quadruple test is the best test for
      women who first attend in the second trimester. There is no justification for
      retaining the Double (alpha-fetoprotein and hCG) or Triple (alpha-fetoprotein,
      uE3, and hCG) tests, or nuchal translucency alone (with or without maternal age)
      in antenatal screening for Down's Syndrome.

PMID- 16104674
TI  - First trimester screening: the BUN study.
AB  - First trimester risk assessment for trisomies 21 and 18 is rapidly transitioning
      from an investigational procedure performed at a few major centers to the
      clinical arena. The BUN study (Biochemistry, Ultrasound, Nuchal translucency) was
      conceived to evaluate the performance of first trimester screening using PAPP-A,
      free beta HCG, and ultrasound measurement of the nuchal translucency when
      introduced into practice. Over a 4-year period, 13 prenatal diagnostic centers
      evaluated over 8500 patients and reported an 85.2% trisomy 21 detection rate with
      a 9.4% false positive rate. Further evaluation of the data revealed that, once
      training and experience were accomplished, sonographers could perform NT
      measurements consistent with reported standards. In approximately half of the
      patients enrolled in the study, second trimester serum analytes were obtained
      leading to additional trisomy 21 detection but with an unacceptably high false
      positive rate. A "sequential contingency" screening approach using both first and
      second trimester values in some patients may provide the additional detection
      afforded by measuring second trimester analytes with a limited invasive procedure
      rate.

PMID- 16104675
TI  - First and second trimester evaluation of risk for fetal aneuploidy: the secondary
      outcomes of the FASTER Trial.
AB  - The FASTER Trial was a multicenter National Institute of Child Health and Human
      Development sponsored study of Down syndrome screening in a large unselected
      obstetric population using first and second trimester maternal serum markers and
      first trimester nuchal translucency sonography. The following paper will describe
      the FASTER Trial. It will review the outcomes of pregnancies complicated by
      cystic hygroma and the FASTER Trial's findings regarding first trimester nasal
      bone ultrasonography and screening for aneuploidy. Although the study's first and
      foremost goal was to compare various first and second trimester methods of
      screening for Down syndrome, the FASTER Trial has revealed a wealth of
      information not only on screening for aneuploidy but also on other obstetric
      issues.

PMID- 16104676
TI  - Patient and health professional acceptance of integrated serum screening for Down
      syndrome.
AB  - Integrated testing for Down syndrome combines first trimester maternal serum and
      nuchal translucency (NT) measurements with second trimester maternal serum
      measurements into a single second trimester Down syndrome risk. A variant of
      integrated testing, the integrated serum test, requires only the serum
      measurements and may be more suitable for widespread use in the general pregnancy
      population. Concern has been voiced that women will find the delay associated
      with waiting for screening results unacceptable for either fully integrated
      (including NT measurements) or integrated serum testing. To address this issue,
      we surveyed 60 women from a population of 8773 women enrolled in an integrated
      serum screening intervention trial in Maine. The women all had also undergone
      traditional second trimester screening 1 to 2 years earlier. All 60 women
      remembered having the integrated serum test, and 59 remembered having a prenatal
      test in their previous pregnancy. Three-quarters of women did not experience
      anxiety relating to the wait for final results in the second trimester, and 95%
      would consider being screened by the integrated serum test in a future pregnancy.
      Women receiving prenatal care at the primary care level are prepared to wait
      until the second trimester for more accurate Down syndrome risk estimates on
      which to base their decision-making.

PMID- 16104677
TI  - Down syndrome screening in the first and/or second trimester: model predicted
      performance using meta-analysis parameters.
AB  - OBJECTIVE: To predict the screening performance for 17 policies currently in use
      or being considered for the near future. METHODS: Multivariate Gaussian modeling
      using parameters derived from published meta-analyses and new meta-analyses for
      gestation-specific nuchal translucency and between trimester correlations.
      RESULTS: For a 1% to 5% false-positive rate, first trimester screening achieved
      detection rates up to 16% to 25% higher than the best second trimester
      combination. Screening in both trimesters sequentially could yield an even
      greater increase in detection of 24% to 35%. The most efficient sequential policy
      was contingent screening, which has a high detection rate with only 15% of women
      needing second trimester tests. CONCLUSION: Modeling with meta-analysis derived
      parameters provides a reliable guide for policy and favors a contingent screening
      policy. The widespread practice of calculating first and second trimester risks
      separately should be abandoned.

PMID- 16104678
TI  - First-trimester risk assessment: twin gestations.
AB  - OBJECTIVE: To determine the role of first-trimester screening in multiple
      gestations. MATERIALS AND METHODS: A review of the literature revealed numerous
      studies in this area. However, most of the studies involved first-trimester
      singleton pregnancies. RESULTS: The few studies that reviewed the experience with
      multiple gestations demonstrated feasibility of this technique. However, the
      detection rate for twin gestations was less than that of singleton gestations.
      CONCLUSION: Although the data support the value of screening twins with
      biochemistry and ultrasound in the first trimester, further study is necessary to
      determine the most sensitive method.

PMID- 16104679
TI  - First trimester screening: economic implications.
AB  - The implementation of new strategies for the detection of Down syndrome will have
      economic implications. These economic considerations must be considered before
      implementation, since resources are limited and health care costs in the Unites
      States are soaring. Economic analyses of prenatal diagnosis have unique
      challenges that must be considered. Most analyses include only direct medical
      costs, ignoring indirect and intangible costs.

PMID- 16104680
TI  - First trimester Down syndrome screening: public health implications.
AB  - Down syndrome (DS) screening has been an integral part of routine prenatal
      screening for the last three decades. Recent efforts have been directed at
      developing additional non-invasive prenatal screening techniques that could not
      only improve sensitivity of prenatal screening, but also be employed in the first
      trimester to offer earlier diagnostic and interventional opportunities. Nuchal
      translucency has proven to be an effective and cost-effective screening test
      that, when combined with serum markers (hCG and pregnancy-associated plasma
      protein [PAPP-A]) in the first and/or second trimester, broadens the diagnostic
      possibilities and improves the diagnostic capabilities of current prenatal DS
      screening methods. Despite the potential benefits, significant operational issues
      regarding access to and availability of such testing may limit its widespread
      application and necessitates the maintenance of both non-sonographic and second
      trimester screening methods. The implementation of first trimester DS testing
      requires the development and maintenance of nationally standardized quality
      control systems to ensure the reliability of serum and ultrasound measurements
      and the accurate assessment of risk. Future efforts to improve prenatal screening
      should continue to emphasize the need for improved access to all aspects of
      prenatal care, stress the importance of provider education and the necessity for
      extensive patient counseling, and reinforce the role of patient education and
      choice.

PMID- 16104681
TI  - Nuchal translucency-based Down syndrome screening: barriers to implementation.
AB  - Nuchal translucency sonography represents an important step forward in screening
      for Down syndrome. It is likely that a range of screening programs that rely on
      nuchal translucency sonography will become popular for general population
      screening. However, a number of practical implementation issues remain to be
      resolved before widespread utilization of this technique can be endorsed. This
      paper addresses some of these issues, including sonographer training,
      standardized nuchal translucency sonography protocol, ongoing nuchal translucency
      quality assurance programs, how to interpret Down syndrome risk, availability of
      first trimester diagnosis, and how to combine screening tests across different
      gestational ages.

PMID- 16104682
TI  - Clinical implications of the ethics of informed consent for first-trimester risk
      assessment for trisomy 21.
AB  - OBJECTIVE: We identify the clinical implications of the ethics of informed
      consent for risk assessment for trisomy 21. FINDING: Based on the ethics of
      informed consent, we find that routinely offering first-trimester risk assessment
      in centers qualified to provide it is ethically obligatory, and routinely
      withholding the results of first-trimester risk assessment is ethically
      unjustified. CONCLUSION: The ethics of informed consent is an essential dimension
      of first-trimester risk assessment for trisomy 21.

PMID- 16104683
TI  - Comment on "Pallas and the Centaur".

PMID- 16104684
TI  - Tailoring porphyrins and chlorins for self-assembly in biomimetic artificial
      antenna systems.
AB  - There is much diversity in the way in which photosynthetic organisms harvest
      sunlight. In chromophore-protein complexes, an exact orientation of pigments by
      the protein matrix ensures an efficient stepwise energy transfer to the reaction
      center where charge separation occurs. The charge separation and subsequent
      electron transfer steps are, however, very similar in all organisms, proving that
      there must exist a common ancestor. The architectural principle of chromophore
      protein complexes is too complicated to be replicated in artificial light
      harvesting devices. A simpler principle employs self-assembling chromophores that
      early green photosynthetic bacteria use in their chlorosomal antenna systems.
      Efforts in mimicking this self-assembly algorithm with fully synthetic pigments
      are presented. The fact that, as in the natural system, after self-assembly,
      concentration quenching is not operating due to the very orderly manner in which
      the chromophores are positioned lends hope for applications in artificial
      devices, such as hybrid solar cells.

PMID- 16104685
TI  - Diverse world of unconventional hydrogen bonds.
AB  - This Account presents our view of unconventional intermolecular hydrogen bonds
      (HBs) for organometallic complexes and transition-metal or main-group hydrides.
      Over the past decade, low-temperature spectroscopic (IR, UV, and NMR) studies
      combined with theoretical calculations have disclosed the static and dynamic
      features of different HBs. Their guiding role in the proton-transfer processes
      was determined, as well as the energetic characteristics of HB intermediates and
      the activation barriers. Nevertheless, there is still much to explore in terms of
      the prediction of HB properties and control of protonation/deprotonation
      processes.

PMID- 16104686
TI  - Toward the ideal organic light-emitting diode. The versatility and utility of
      interfacial tailoring by cross-linked siloxane interlayers.
AB  - Small molecule and polymer organic light-emitting diodes (OLEDs) show promise of
      revolutionizing display technologies. Hence, these devices and the materials that
      render them functional are the focus of intense scientific and technological
      interest. The archetypical multilayer OLED heterostructure introduces numerous
      chemical and physical challenges to the development of efficient and robust
      devices. It is demonstrated here that robust, pinhole-free, conformal, adherent
      films with covalently interlinked structures are readily formed via self
      assembling or spin-coating organosilane-functionalized molecular precursors at
      the anode-hole transport layer interface. In this manner, molecularly
      "engineered" hole transport and hydrocarbon anode functionalization layers can be
      introduced with thicknesses tunable from the angstrom to nanometer scale. These
      investigations unequivocally show that charge injection and continuity at the
      anode-hole transport layer interface, hence OLED durability and efficiency, can
      be substantially enhanced by these tailored layers.

PMID- 16104687
TI  - Bioinspired surfaces with special wettability.
AB  - Biomimetic research indicates that many phenomena regarding wettability in
      nature, such as the self-cleaning effect on a lotus leaf and cicada wing, the
      anisotropic dewetting behavior on a rice leaf, and striking superhydrophobic
      force provided by a water strider's leg, are all related to the unique micro- and
      nanostructures on the surfaces. It gives us much inspiration to realize special
      wettability on functional surfaces through the cooperation between the chemical
      composition and the surface micro- and nanostructures, which may bring great
      advantages in a wide variety of applications in daily life, industry, and
      agriculture. This Account reviews recent progress in these aspects.

PMID- 16104688
TI  - Toward rapid, "green", predictable microwave-assisted synthesis.
AB  - Continuous and batch microwave reactors were constructed for efficient, "green"
      synthesis with low-boiling solvents at high temperature in closed vessels.
      Capabilities for rapid heating and cooling, concurrent heating and cooling, and
      differential heating facilitated novel chemical reactions and processes.
      Commercial microwave systems based on these developments are available. Times
      required for conventional reactions typically are decreased by 2-3 orders of
      magnitude. Green processes also have resulted through use of less or no catalyst,
      readily recyclable solvents, or media and yields that are often higher than
      normal. Complementary interactive software for calculating optimal conditions was
      developed.

PMID- 16104689
TI  - Mechanism for transduction of the ligand-binding signal in heme-based gas sensory
      proteins revealed by resonance Raman spectroscopy.
AB  - Gene analysis has revealed a variety of new heme-containing gas sensory proteins
      in organisms ranging from bacteria to mammals. These proteins are composed of
      sensor, communication, and functional domains. The sensor domain contains a heme
      that binds effector molecules such as NO, O2, or CO. Ligand binding by the sensor
      domain modulates the physiological role of the protein, such as DNA binding in
      the case of transcriptional factors or the catalytic reaction rate in the case of
      enzymes. This Account summarizes resonance Raman (RR) studies, including static
      and time-resolved measurements, which have enabled elucidation of the mechanisms
      by which binding of specific target molecule by the sensor domain is transduced
      to alteration of the functional domain. These studies have shown that signals can
      be conveyed from the heme to the functional domain via three different pathways:
      (i) a distal pathway, (ii) a proximal pathway, and (iii) a heme peripheral
      pathway.

PMID- 16104690
TI  - Alfred Werner revisited: the coordination chemistry of anions.
AB  - A series of macrocyclic receptors were designed to probe the influence of four
      factors, hydrogen bonding, charge, dimensionality, and topology, on anion
      binding. Monocyclic and bicyclic polyammonium and polyamide receptors were
      synthesized from either 2,2'-diaminodiethylamine derivatives (dien) or 2,2',2''
      aminoethylamine (tren) building blocks, plus aromatic or heterocyclic spacers.
      Supramolecular complexes of these hosts with three simple anion topologies were
      probed: spherical (halides), trigonal planar (nitrate), and tetrahedral
      (sulfate). Results indicate a number of corollaries with transition-metal
      coordination chemistry in terms of binding concepts such as the chelate effect
      and dual valencies, as well as geometries for anion complexes that are strikingly
      similar to those observed in transition-metal coordination chemistry.

PMID- 16104691
TI  - Generation of cycloalkynes by hydro-iodonio-elimination of vinyl iodonium salts.
AB  - Cyclohexynes can be generated efficiently from 1-cyclohexenyliodonium salts with
      acetate or other bases via the E2 and E1 mechanism. The observed regioselectivity
      of nucleophilic addition to substituted cyclohexynes conforms to the LUMO
      populations: the less deformed acetylenic carbon is more electrophilic.
      Cycloheptyne can form by the E1-type elimination via 1,2-rearrangement from
      cyclohexylidenemethyliodonium salt under very weakly basic conditions.

PMID- 16104693
TI  - Properties of the emitting state of the green fluorescent protein resolved at the
      CASPT2//CASSCF/CHARMM level.
AB  - A "brute-force" ab initio CASPT2//CASSCF/CHARMM computational approach is
      employed to investigate the properties of the emitting state of the wild-type
      green fluorescence protein. The results indicate that the emitting moiety
      corresponds to a slightly perturbed H2O- - -chromophore complex. Thus, the
      protein matrix seems to be designed in such a way to mimic an environment that is
      more similar to gas-phase than water solution.

PMID- 16104694
TI  - Hydrogen-bonded anionic rosette networks assembled with guanidinium and C3
      symmetric oxoanion building blocks.
AB  - Two premeditated anionic rosette-layer architectures have been constructed using
      guanidinium and ubiquitous C3-symmetric oxoanions that carry unequal charges,
      employing bulky organic cations as interlayer templates. The undulate guanidinium
      carbonate network occurs in 4[(C2H5)4N+].8[C(NH2)3+].3(CO3)2-.3(C2O4)2-.2H2O, in
      which the disordered (C2H5)4N+ guests are accommodated in pouches and channels
      within a complex three-dimensional hydrogen-bonded host framework. In
      [(C2H5)4N+]2.[C(NH2)3+].[1,3,5-C3H3(COO-)3].6H2O, ordered (C2H5)4N+ cations are
      sandwiched between planar guanidinium-trimesate host layers whose honeycomb
      cavities are tightly fitted with flattened-chair (H2O)6 clusters of symmetry 2.

PMID- 16104695
TI  - Designing interfaces that function to facilitate charge injection in organic
      light-emitting diodes.
AB  - Layer-by-layer (LbL) assembly of triarylamine (TAA)-containing polymers has been
      applied for anode functionalizations in organic light-emitting diodes (OLEDs).
      Surface work function of the ITO electrodes was significantly altered with the
      functionalizations, and the values changed depending on electron affinity of the
      substituents (X) on the TAA units. When the functionalized ITO electrodes were
      utilized for the conventional TPD/Alq OLED, the multilayers of P1 (X = 4-OMe) and
      P2 (X = none) were found to promote better energy matching at the ITO/TPD
      interface to reduce the hole injection barrier. Furthermore, the multilayers
      having heterodeposited structure of several TAA polymers provided stepped and
      graded electronic profiles to facilitate hole mobility from ITO to TPD, so that
      the resulting OLED devices can exhibit appreciably reduced turn-on voltage and
      higher luminous intensities.

PMID- 16104696
TI  - NMR heteronuclear correlation between quadrupolar nuclei in solids.
AB  - We show for the first time that it is possible to acquire high-resolution
      heteronuclear NMR correlation experiments in solid state between second-order
      broadened half integer quadrupolar nuclei (i.e., 27Al and 17O) using the scalar J
      coupling. The sensitivity of the experiment is dramatically improved at high
      fields (gain proportional to the fourth power of the principal field) with a
      combination of signal enhancement techniques. This turns a challenging experiment
      into a real tool. We apply this experiment to characterize a calcium aluminate
      glass in which we prove the presence of tricluster mu3 oxygen sites and describe
      the signature of their directly bonded aluminum sites. Applications involve a
      large range of possible pairs of quadrupolar nuclei in different materials, such
      as glasses, porous or mesoporous framework materials, zeolites, hybrid organic
      inorganic, and bioinvolved materials.

PMID- 16104697
TI  - Conducting AFM and 2D GIXD studies on pentacene thin films.
AB  - Among all organic semiconductors, pentacene has been shown to have the highest
      thin film mobility reported to date. The crystalline structure of the first few
      pentacene layers deposited on a dielectric substrate is strongly dependent on the
      dielectric surface properties, directly affecting the charge mobility of
      pentacene thin film OTFTs. Herein, we report that there is a direct correlation
      between the crystalline structure of the initial submonolayer of a pentacene film
      and the mobility of the corresponding 60-nm-thick films showing terrace-like
      structure, as confirmed by 2D grazing-incidence X-ray diffraction and atomic
      force microscopy. Specifically, multilayered pentacene films, grown from single
      crystal-like faceted islands on HMDS-treated surface, have shown much higher
      charge mobility (mu = 3.4 +/- 0.5 cm2/Vs) than those with polycrystalline
      dendritic islands (mu = 0.5 +/- 0.15 cm2/Vs) on OTS-treated ones.

PMID- 16104698
TI  - Dynamic and fluorescent nanoscale phenanthroline/terpyridine zinc(II) ladders.
      Self-recognition in unlike ligand/like metal coordination scenarios.
AB  - A new coordination kit, the HETTAP approach, is described, which allows one to
      prepare supramolecular heteroleptic metal phenanthroline/terpyridine racks and
      ladders in basically quantitative yield. Due to the dynamic nature of the
      nanoladder structures, a two-step double-transmetalation and scenarios with like
      metal/unlike ligand recognition were realized.

PMID- 16104699
TI  - Measured depletion of ions at the biomembrane interface.
AB  - Expected from theory and simulations, depletion of ions at fuzzy biomembrane
      interfaces has long eluded experiments. Here, we show how salt exclusion can be
      accurately measured by surprisingly simple yet accurate benchtop measurements.
      Multilamellar aggregates of common phospholipids sink in low salt but float in
      salt solutions that are much less dense than the lipid itself. By manipulating
      bath and lipid densities, using heavy water and varied lipid chain length, we
      obtain accurate exclusion curves over a wide range of KCl and KBr concentrations.
      While maintaining a constant width at low salt, the exclusion layer decreases in
      high salt, following the Debye screening length. Consistent with interfacial
      accumulation of polarizable ions, bromide salts are less excluded than chloride,
      with an attraction of approximately 2kBT per Br- ion. So far neglected in
      theoretical descriptions, the competition between salt exclusion and binding is
      critical to understanding membrane interactions and specific ionic effects.

PMID- 16104700
TI  - A colorimetric sensor array for organics in water.
AB  - Molecular recognition of organic compounds in aqueous solutions is inherently
      challenging due to the potential interference from the very high concentration of
      water. Here we present a simple colorimetric sensor array that probes a wide
      range of chemical properties. By printing hydrophobic dyes on a hydrophobic
      membrane, sensor arrays are easily prepared that provide substantial chemical
      selectivity for the identification and quantification of various organics (both
      single compounds and complex mixtures) dissolved in water. It is possible to
      differentiate easily even among closely related organic compounds. Upon immersion
      in aqueous solutions, digital imaging of the dye array before and after exposure
      to an analyte provide a color change profile that is a fingerprint for the
      organic components of the solution. Facile identification of a wide variety of
      aqueous organic solutions is possible over a concentration range of 0.1 M to 1
      muM. Complex mixtures present no inherent difficulty; for example, a series of
      commercial soft drinks were easily distinguished using the colorimetric sensor
      array approach.

PMID- 16104701
TI  - Octahedral non-heme non-oxo Fe(IV) species stabilized by a redox-innocent N
      methylated cyclam-acetate ligand.
AB  - The ligand 1,4,8-tri-N-methyl-1,4,8,11-tetraazacyclotetradecane-11-acetic acid
      (Me3cyclam-acetic acid) has been synthesized by Eschweiler-Clarke methylation of
      cyclam-acetic acid, and the iron(III) complex [(Me3cyclam-acetate)FeN3]PF6, 1,
      has been synthesized, which has been found to have significantly different
      properties than its unmethylated analogue, [(cyclam-acetate)FeN3]PF6, 2. Whereas
      the iron ion in 2 is low spin with S = 1/2, 1 is found to be high spin at
      temperatures above 100 K, though low-spin species are observed at lower
      temperatures, indicating a spin crossover phenomenon. The iron(II) species 1red
      is electrochemically more accessible than 2red since the Fe2+/3+ redox wave in 1
      appears approximately 350 mV more positive than the corresponding wave in 2.
      Also, 1 displays a reversible Fe3+/4+ redox wave, which is irreversible in 2,
      denoting that the Fe(IV) species 1ox is kinetically stable. 1red and 1ox have
      been generated electrochemically in solution and studied spectroscopically.
      Mossbauer spectroscopy has confirmed that, in both reduction and oxidation, iron
      is the redox center, that 1red is high spin (S = 2), and that 1ox is low spin (S
      = 1), in contrast to 2red which is low spin and 2ox which could not be isolated.

PMID- 16104702
TI  - Dual modulation of a molecular switch with exceptional chiroptical properties.
AB  - The ability to modulate the chiroptical properties of optically active molecules
      induced by external stimuli such as light, heat, and electrical fields allows for
      the design and development of molecular switches, memory devices, sensors, and
      photonic devices. A helical o-terphenyl compound functionalized with
      photoresponsive azobenzene and electroactive imide groups is designed as a dual
      mode chiroptical molecular switch. Its exceptional optical activity (e.g.,
      [alpha]436 = -9500) can be changed and modulated through photoisomerization of
      the azobenzene moiety using UV and visible light. Reversible modulation by
      electrochemical means was also achieved through the redox reaction occurring at
      the imide group. Large chiroptical read-out signals were observed during the
      redox cycles as indicated by the molar ellipticity values as high as 285,000
      deg.cm2.dmol-1. Exceptionally high optical activity and large responses to both
      light and electrical bias make this chiral molecule suitable for the development
      of new molecular switches, sensors, and other optical devices.

PMID- 16104703
TI  - Carbon nanotube graphoepitaxy: highly oriented growth by faceted nanosteps.
AB  - Single-wall carbon nanotubes grow along self-assembled nanosteps of annealed
      miscut C-plane sapphire. Depending on the miscut orientation and annealing
      conditions, graphoepitaxy leads to the formation of either unprecedentedly
      straight and parallel nanotubes, with angular deviations as small as +/-0.5
      degrees , or to wavy nanotubes loosely conformal to sawtooth-shaped faceted
      nanosteps.

PMID- 16104704
TI  - Alternating hydrophilic and hydrophobic pockets in the channel structures of
      organostannoxane prismanes: preferential confinement of guest molecules.
AB  - A hydroxyl-rich hexameric organooxotin prismane has been prepared by reaction of
      n-BuSn(O)OH with 9-hydroxy-9-fluorenecarboxylic acid. The supramolecular
      structure of this cage shows channels with hydrophobic and hydrophilic segments,
      which selectively entrap guest molecules.

PMID- 16104705
TI  - Ribose 2'-F labeling: a simple tool for the characterization of RNA secondary
      structure equilibria by 19F NMR spectroscopy.
AB  - We present a facile 19F NMR spectroscopic approach for the characterization of
      bistable RNA. The concept is based on the site-specific labeling of RNA with
      single 2'-deoxy-2'-fluoro (2'-F) nucleosides. Depending on the position of the 2'
      F label (either within a double helix or a single-stranded region), significantly
      different 19F chemical shifts were observed and assigned to the particular
      alternative folds. This has been exemplified for a series of bistable RNAs. The
      approach is promising for the detailed investigation of complex RNA folding
      pathways.

PMID- 16104706
TI  - Synthesis and structure of the bidimensional zeolite ITQ-32 with small and large
      pores.
AB  - A new bidimensional zeolite containing 8R and 12R pores, denoted as ITQ-32, has
      been synthesized and its structure solved from powder X-ray diffraction data.
      This zeolite presents a relatively large pore volume (0.16 cm3/g) and pore
      apertures of 3.5 x 4.3 A and can be prepared as a nearly pure silica zeolite and
      as aluminosilicate. In the latest case, acidic properties are developed.

PMID- 16104707
TI  - Filtered backprojection for the reconstruction of a high-resolution (4,2)D CH3-NH
      NOESY spectrum on a 29 kDa protein.
AB  - Projection-reconstruction (PR) NMR enables rapid collection of multidimensional
      NMR data. NOESY represents a particularly difficult challenge for currently
      existing reconstruction algorithms, as it requires the quantitative
      reconstruction of an unknown number of peaks, at full sensitivity. We have
      demonstrated the successful application of PR-NMR to NOESY by determining the 4D
      methyl/amide NOESY spectrum of a 29 kDa protein, human carbonic anhydrase II,
      from 2D projections, using filtered backprojection for reconstruction. Compared
      with a 3D control spectrum, all expected peaks were faithfully reconstructed,
      with correct volumes and with no artifacts. Filtered backprojection thus provides
      a way to obtain high-resolution 4D NOESY data in the time required for
      conventional 3D data collection.

PMID- 16104708
TI  - Phosphorescent excited state of [Au2[(Ph2Sb)2O]3]2+: Jahn-Teller distortion at
      only one gold(I) center.
AB  - Dinuclear three-coordinate Au(I) complex [Au2{(Ph2Sb)2O}3](ClO4)2 1 displays an
      interesting phosphorescent behavior in which a large Stokes' shift is observed.
      Ab initio calculations show that the main distortion for the first triplet
      excited state, which is responsible for the luminescence behavior of complex 1,
      is a Jahn-Teller distortion for only one of the Au(I) centers together with a
      gold-gold distance shortening. This behavior could be extrapolated to other
      phosphorescent dinuclear three-coordinate Au(I) complexes.

PMID- 16104709
TI  - A highly active, isospecific cobalt catalyst for propylene oxide polymerization.
AB  - A highly active cobalt complex ((salph)CoOAc; salph = N,N'-bis(3,5-di-tert
      butylsalicylidine-1,2-benzenediamine)) was discovered for the isospecific
      polymerization of rac-propylene oxide.

PMID- 16104710
TI  - G-quartet-induced nanoparticle assembly.
AB  - The design and synthesis of a new class of gold nanoparticle with guanosine
      monophosphate derivatives or G-rich oligonucleotides as their surface ligands are
      described. These nanoparticles spontaneously form macroscopic assemblies at low
      temperature and relatively high salt concentrations, which is attributed to the
      cooperative formation of guanosine quartets and G-quadruplexes between the
      individual nanoparticles. Significantly, the solution behavior of these
      nanoparticles is highly controllable by adjusting solution parameters (including
      temperature, ionic strength, and ion species) and the sequence of the G-rich
      oligonucleotide

PMID- 16104711
TI  - Side-chain chiral centers of amino acid and helical-screw handedness of its
      peptides.
AB  - Both diastereomeric right-handed (P) and left-handed (M) 310-helices exist in
      homopeptides having twelve chiral centers at the side-chain bicyclic skeletons.

PMID- 16104712
TI  - B-allyl-10-Ph-9-borabicyclo[3.3.2]decanes: strategically designed for the
      asymmetric allylboration of ketones.
AB  - The simple and efficient syntheses of B-allyl-10-(phenyl)-9
      borabicyclo[3.3.2]decane (1) in both enantiomeric forms are reported. The
      remarkable enantioselectivity (81-99% ee) of these reagents in the allylboration
      process at -78 degrees C is only modestly diminished when the process is
      conducted at 0 degrees C, a phenomenon attributable to its rigid bicyclic
      structure. In addition to providing the homoallylic alcohols 6 efficiently (70
      92%), the procedure also permits the efficient recovery of the chiral boron
      moiety (67-82%) as an air-stable crystalline N-methylpseudoephedrine complex 4
      for the direct regeneration of 1 with allylmagnesium bromide in ether (98%). The
      reagent gives predictable stereochemistry, providing a strategically designed
      "chiral pocket" which is particularly receptive to leading methyl groups (e.g.,
      methyl ethyl ketone, 87% ee).

PMID- 16104713
TI  - Bioelectrochemical propulsion.
AB  - A carbon fiber having a terminal glucose oxidizing microanode and an O2 reducing
      microcathode is propelled at the water-O2 interface. The electron current in the
      fiber is accompanied by a flux of hydrated protons that is so fast at the
      solution-air interface, where the viscous drag is small, that the fiber's
      velocity is 1 cm s-1.

PMID- 16104714
TI  - Ferrocene-containing cationic lipids: influence of redox state on cell
      transfection.
AB  - A ferrocene-containing, redox-active cationic lipid that can be transformed using
      electrochemical methods yields large differences in cell transfection depending
      on the oxidation state of the lipid. Expression of enhanced green fluorescent
      protein and firefly luciferase occurs at very high levels when DNA lipoplexes are
      formulated using the lipid in the reduced state. In contrast, transfection is
      negligible when oxidized lipid is used. These observations suggest the basis of a
      general method that could be used to transform inactive lipoplex formulations to
      an active form through the application of externally applied electrical
      potentials. The ability to activate lipoplexes toward transfection
      electrochemically and "on demand" could create new opportunities to deliver DNA
      in vitro and in vivo with both spatial and temporal control.

PMID- 16104715
TI  - Organic-inorganic hybrid liquid crystals: thermotropic mesophases formed by
      hybridization of liquid-crystalline phosphates and monodispersed alpha-Fe2O3
      particles.
AB  - A novel organic-inorganic hybrid thermotropic liquid crystal (LC) is developed by
      the hybridization of an organic phosphate having a mesogenic core and
      monodispersed alpha-Fe2O3 particles with different shapes through the specific
      adsorption of the phosphate group to the surfaces parallel to the c-axis of the
      alpha-Fe2O3. The hybrid LC shows thermotropic nematic or cubic liquid
      crystallinity in wide ranges of temperatures. Variable-temperature small-angle X
      ray measurements reveal that the spontaneous formation of periodic structure by
      the hybridization induces the thermotropic liquid crystallinity. This technique
      would lead development of novel types of dynamic functional materials with multi
      responsiveness to magnetic and electric fields.

PMID- 16104716
TI  - Structural elucidation of sumanene and generation of its benzylic anions.
AB  - The structure of sumanene in a solid state was elucidated. The silyl-substituted
      sumanene was stereoselectively synthesized through generation of the benzylic
      anions of sumanene.

PMID- 16104717
TI  - An opened route to 1,3-dimethylenecyclobutanes via sequential ruthenium-catalyzed
      [2 + 2] cycloaddition of allenyl boronate and palladium Suzuki coupling.
AB  - The regioselective head-to-head [2 + 2] cyclodimerization of allenyl boronate
      catalyzed by the ruthenium catalyst [Cp*RuCl(COD)] leads to a novel diboronated
      1,3-dimethylenecyclobutane. Consecutive palladium-catalyzed C-C couplings open a
      route to novel disubstituted 1,3-dimethylenecyclobutane species. The X-ray
      crystalline structure of the phenyl-substituted 1,3-dimethylenecyclobutane is
      provided.

PMID- 16104718
TI  - Synthesis and characterization of single-crystalline alkali titanate nanowires.
AB  - A simple, one-step method has been utilized to synthesize functional ternary
      alkali titanate nanowires of single crystallinity. Nanostructural
      characterization shows that the nanowires are Na2Ti6O13 with [010] growth
      direction and KTi8O16.5 with [001] growth direction.

PMID- 16104719
TI  - Catalytic asymmetric Staudinger reactions to form beta-lactams: an unanticipated
      dependence of diastereoselectivity on the choice of the nitrogen substituent.
AB  - There are relatively few methods for the catalytic asymmetric synthesis of beta
      lactams, and those that have been reported are generally cis selective. This
      communication describes the first catalytic enantioselective Staudinger reactions
      that preferentially furnish trans beta-lactams (trans = relationship of Ph to
      R1). The key to this method is the use of an N-triflyl protecting group for the
      imine. Along with serving as interesting targets in their own right, N-triflyl
      beta-lactams readily react with nucleophiles to generate useful families of
      compounds, such as gamma-amino alcohols and beta-amino acids.

PMID- 16104720
TI  - Semisynthetic tellurosubtilisin with glutathione peroxidase activity.
AB  - Reaction of the hydroxyl group of serine-221 of subtilisin with
      phenylmethanesulfonylfluoride followed by nucleophilic substitution with sodium
      hydrogen telluride, a semisynthetic telluroprotein, tellurosubtilisin, was
      prepared. Tellurosubtilisin, which displays high substrate specificity for
      aromatic thiols, exhibits remarkable peroxidase activity and catalyzes the
      reduction of hydrogen peroxide by 3-carboxy-4-nitrobenzenethiol 20 000 times more
      efficiently than diphenyl diselenide.

PMID- 16104721
TI  - Characterization of reactive sites in supported catalysts by 51V/15N rotational
      echo double resonance NMR spectroscopy: formation of phenylimido groups at
      surface-bound oxovanadium sites.
AB  - Silica-supported oxovanadium groups were reacted in a gas-solid reaction with
      aniline at 175 degrees C. The reaction was clean as monitored in situ by UV-vis
      spectroscopy and resulted in the elimination of water as the principal product of
      the reaction and the disappearance of the terminal V=O stretch in the Raman
      spectrum. 15N MAS solid-state NMR spectroscopy showed only a single nitrogen
      containing species on the surface. Proton-dephased 15N NMR showed only weak
      attenuation of its intensity, indicating that there are no protons directly
      bonded to the nitrogen. The formation of a vanadium-imido covalent bond was
      characterized by 51V/15N rotational echo double resonance NMR spectroscopy where
      the quadrupolar 51V nucleus was monitored and the spin-1/2 15N nucleus was
      dephased.

PMID- 16104722
TI  - Dual Lewis acid-Lewis base activation in enantioselective cyanation of aldehydes
      using acetyl cyanide and cyanoformate as cyanide sources.
AB  - Dual activation by a chiral Lewis acid and an achiral or chiral Lewis base
      enabled cyanation of both aromatic and aliphatic aldehydes with acetyl cyanide
      and ethyl cyanoformate to provide direct access to O-acetylated and O
      alkoxycarbonylated cyanohydrins, respectively, under mild conditions. With a
      combination of a Ti-salen catalyst and Et3N, benzaldehyde was converted to the O
      acetylated cyanohydrin with 94% ee within 10 h at -40 degrees C in 89% isolated
      yield.

PMID- 16104723
TI  - Biosynthesis of the beta-amino acid moiety of the enediyne antitumor antibiotic C
      1027 featuring beta-amino acyl-S-carrier protein intermediates.
AB  - The enediyne antitumor antibiotic C-1027 chromoprotein is produced by
      Streptomyces globisporus. The biosynthesis of the (S)-3-chloro-4,5-dihydroxy-beta
      phenylalanine moiety (boxed) of the C-1027 chromophore (1) from l-tyrosine (3)
      and its incorporation into 1 are catalyzed by six enzymes: SgcC, SgcC1, SgcC2,
      SgcC3, SgcC4, ShcC5. In vivo and in vitro characterization of these enzymes
      delineated this pathway, unveiling a novel strategy for beta-amino acid
      modification featuring beta-amino acyl-S-carrier protein intermediates. These
      findings shed new light into beta-amino acid biosynthesis and present a new
      opportunity to engineer the C-1027 biosynthetic machinery for the production of
      novel analogues as exemplified by 20-deschloro-C-1027 (4), 20-deschro-22
      deshydroxy-C-1027 (5), and 22-deshydroxy-C-1027 (6).

PMID- 16104724
TI  - Preparation of iron amido complexes via putative Fe(IV) imido intermediates.
AB  - The isolation and characterization of monomeric Fe(III) amido complexes with
      hybrid ureate/amidate ligands is described. An aryl azide serves as the source of
      the amido ligand in preparing the complexes from trigonal monopyramidal Fe(II)
      precursors. Aryl azides more commonly react with transition metal complexes by a
      two-electron oxidation process to yield imido complexes, suggesting that the
      Fe(III) amido complexes may be formed from high valent species by hydrogen atom
      abstraction from an external species. The mechanistic basis for formation of the
      amido complexes is investigated using substrates that readily donate hydrogen
      atoms. Results from these experiments suggest that the Fe(III) amido complexes
      are generated from Fe(IV) imido intermediates that can facilitate homolytic X-H
      bond cleavage. The Fe(III) amido complexes are high spin (S = 5/2) with a strong
      absorbance band at lambdamax approximately 600 nm and extinction coefficients
      between 2000 and 3000 M-1 cm-1. These complexes are hygroscopic, reacting with 1
      equiv of water to produce the corresponding Fe(III)-OH complexes and p-toluidine.

PMID- 16104725
TI  - Enantioselective organocatalytic Michael additions of aldehydes to enones with
      imidazolidinones: cocatalyst effects and evidence for an enamine intermediate.
AB  - An enantioselective intermolecular Michael addition of aldehydes to enones
      catalyzed by imidazolidinones has been achieved. Chemoselectivity (Michael
      addition vs aldol) can be controlled through judicious choice of hydrogen-bond
      donating cocatalysts. The optimal imidazolidinone/hydrogen-bond-donor pair
      affords Michael addition products in excess of 90% ee. Furthermore, we have
      isolated and characterized an enamine intermediate and demonstrated its efficacy
      as a nucleophile in the observed Michael addition reactions.

PMID- 16104726
TI  - Unexpected Si:Al effect on the binary mixtures liquid phase adsorption
      selectivities in faujasite zeolites.
AB  - A batch technique was applied to determine the equilibrium adsorption of benzene
      from its benzene/octane and benzene/octene mixture on NaX (Si:Al 1.20) and NaY
      (Si:Al 2.79) in liquid phase. Benzene was preferentially adsorbed from both
      mixtures on NaX and NaY. Regardless whether octane or octene was present in the
      binary mixture, benzene was adsorbed more selectively on the high-silica NaY
      compared to NaX, which contained more cations. The presence of cations on the
      SIII/SIII' site inside the supercages of NaX causes a more difficult hosting of
      benzene inside the supercages of NaX and especially on the 12-membered ring site.
      However, at sufficiently high external benzene concentration (>10 mol %), the 12
      membered ring site of NaX will be occupied by benzene, leading to a maximum
      adsorption capacity of five benzenes per supercage on both NaX and NaY. The
      double bond present inside octene allows the molecules to compete for the
      adsorption sites with benzene. The competitive effect of octene prevents the
      fifth benzene molecule to adsorb in the NaX supercage within the investigated
      concentration range.

PMID- 16104727
TI  - Reconstitution of a new cysteine biosynthetic pathway in Mycobacterium
      tuberculosis.
AB  - A new pathway for cysteine biosynthesis has been elucidated in Mycobacterium
      tuberculosis. This pathway involves a protein-bound thiocarboxylate (CysO-SH) as
      the sulfide donor, similar to thiamin biosynthesis. Cysteine synthase M (CysM)
      catalyzes the addition of cysteine to the carboxy terminus of the protein-bound
      thiocarboxylate to generate a CysO-cysteine adduct. A protease, Mec+, hydrolyzes
      the CysO-cysteine adduct to release cysteine and regenerate CysO. Mec+ contains a
      JAMM motif, and this work provides the first functional characterization of the
      JAMM motif in prokaryotes. MoeZ, a paralogue of ThiF, has been shown to transfer
      sulfur onto CysO.

PMID- 16104728
TI  - Nonlinear magnetooptical effects caused by piezoelectric ferromagnetism in F3m
      type Prussian blue analogues.
AB  - The second harmonic generation (SHG) and magnetization-induced SHG (MSHG) of
      AMA[MB(CN)6]-type (F3m) Prussian blue analogues (i.e., CsCo[Cr(CN)6].0.5H2O and
      RbMn[Fe(CN)6]) were observed. A large interaction between the nonlinear optical
      response and magnetic spins was observed in CsCo[Cr(CN)6].0.5H2O. These
      observations of SHG and MSHG imply that AMA[MB(CN)6]-type Prussian blue analogues
      are piezoelectric above the Curie temperature (TC) and piezoelectric ferromagnet
      below TC.

PMID- 16104729
TI  - Ruthenium-catalyzed cycloisomerization of cis-3-en-1-ynes to cyclopentadiene and
      related derivatives through a 1,5-sigmatropic hydrogen shift of ruthenium
      vinylidene intermediates.
AB  - We report a new ruthenium-catalyzed cycloisomerization of unactivated cis-3-en-1
      ynes, which produces substituted cyclopentadiene and related derivatives. The
      mechanism of this cyclization is proposed to involve a [1,5]-sigmatropic hydrogen
      shift of ruthenium-vinylidene intermediates on the basis of deuterium-labeling
      experiments.

PMID- 16104730
TI  - Core-modified expanded porphyrins with large third-order nonlinear optical
      response.
AB  - The third-order nonlinear optical response through measurement of two-photon
      absorption cross-sections (TPACS) for aromatic core-modified expanded porphyrin
      analogues by a femtosecond open aperture Z-scan method is reported. The values
      reported here are among the largest known so far in the literature for any
      organic molecules.

PMID- 16104731
TI  - Radical hydroxyalkylation of C-H bond adjacent to nitrogen of tertiary amides,
      ureas, and amines.
AB  - Tertiary amides, ureas, and amines undergo direct intermolecular addition to
      aldehydes under the Et3B/air conditions, thereby providing a unique and simple
      means for the radical sp3 C-H transformation of nitrogen-containing molecules.

PMID- 16104732
TI  - The activity of Escherichia coli cyclopropane fatty acid synthase depends on the
      presence of bicarbonate.
AB  - Cyclopropane fatty acid (CFA) synthases catalyze the formation of cyclopropane
      rings on isolated and unactivated olefinic bonds within various fatty acids; the
      methylene carbon is derived from the activated methyl group of (S)
      adenosylmethionine. The E. coli enzyme is the prototype for this class of
      enzymes, which include the cyclopropane mycolic acid (CMA) synthases, which are
      potential targets for the design of antituberculosis agents. Crystal structures
      of several CMA synthases have recently been solved, and electron density
      attributed to a bicarbonate ion was found in or near the active site. Because a
      functional assay for CMA synthases has not been developed, the relevance of the
      bicarbonate ion has not been established. CFA synthase is 30-35% identical to the
      CMA synthases that have been analyzed structurally, suggesting that the
      mechanisms of these enzymes are conserved. In this work, we show that indeed the
      activity of CFA synthase requires bicarbonate, and that it is inhibited by
      borate, a planar trigonal molecule that mimics the structure of bicarbonate. We
      also show that substitutions of the conserved amino acids that act as ligands to
      the bicarbonate ion based on the structure of CMA synthases result in drastic
      losses in the activity of the protein.

PMID- 16104733
TI  - Enantioselective organocatalytic allylic amination.
AB  - A new strategy for catalytic enantioselective allylic amination based on
      organocatalysis has been developed. Using a commercially available organocatalyst
      we demonstrate a direct highly enantioselective allylic electrophilic
      functionalization of alkylidene cyanoacetates and malononitriles with
      azodicarboxylates. The reaction is broad in scope and proceeds in high yields and
      with enantioselectivities up to 99%. Furthermore, we demonstrate the synthetic
      utility of the optically active products formed: highly diastereoselective Diels
      Alder reaction, reduction, and formation of optically active building blocks,
      which are found in various important bioactive compounds such as quinacrine,
      chloroquine, and analogues thereof.

PMID- 16104734
TI  - Enantioselective organocatalytic intramolecular Diels-Alder reactions. The
      asymmetric synthesis of solanapyrone D.
AB  - The first direct enantioselective organocatalytic intramolecular Diels-Alder
      reaction has been accomplished. The use of iminium catalysis has provided a new
      catalytic strategy for the enantioselective [4 + 2] cycloisomerization of a wide
      variety of tethered diene-enal systems. The use of imidazolidinones 1 and 2 as
      the asymmetric catalysts has been found to mediate the enantioselective
      construction of [4.4.0] and [4.3.0] ring systems. Application of this methodology
      to the highly efficient asymmetric synthesis of the marine metabolite solanpyrone
      D has also been accomplished. A diverse spectrum of aldehyde substrates can also
      be accommodated in this new organocatalytic transformation. Importantly, this
      technology has been utilized to execute the first enantioselective, catalytic
      Type II IMDA reaction.

PMID- 16104735
TI  - Beta-aryl eliminations from Rh(I) iminyl complexes.
AB  - beta-Aryl eliminations from a series of iminyl complexes to form rhodium aryl
      complexes and free nitriles are reported. Iminyl complexes [Rh(PEt3)3(N=CArAr')]
      were prepared from [Rh(COE)Cl]2, PEt3, LiN(SiMe3)2, and the imines HN=CArAr'. One
      example of these complexes was characterized by X-ray diffraction. Heating of
      these complexes in cyclohexane generated the rhodium aryl complexes and free
      nitriles in high yields; heating in benzene formed the same products in slightly
      lower yields. Complexes with varied aryl groups on the imine were studied to
      assess the migratory aptitudes of the aryl groups. Migration of the o-anisyl
      group occurred much faster than migration of a phenyl group; migration of a
      phenyl group occurred slightly faster than migration of the more electron-rich p
      anisyl group; and migration of a phenyl group occurred slightly faster than
      migration of the more hindered o-tolyl group. Kinetic studies showed that the
      reaction was inverse first-order in the concentration of added phosphine and zero
      order in added nitrile. These results show that the beta-aryl elimination most
      likely occurs by dissociation of phosphine from the starting complex and carbon
      carbon bond cleavage of the resulting 14-electron intermediate.

PMID- 16104736
TI  - Total synthesis of dictyodendrin B.
AB  - A concise total synthesis of dictyodendrin B (1) is reported, a scarce marine
      alkaloid endowed with promising telomerase inhibitory activity. Key steps of the
      chosen route are a reductive cyclization of ketoamide 11 to indole 12 mediated by
      low-valent titanium (from TiCl3 and KC8) followed by a photochemical 6pi
      electrocyclization, which was performed in the presence of Pd/C and nitrobenzene
      to effect concomitant dehydrogenation/aromatization of the product initially
      formed. Regioselective bromination of the resulting pyrrolocarbazole 13 followed
      by lithium/bromine exchange and quenching of the resulting organolithium species
      with p-methoxybenzaldehyde installed the side chain at C2. Oxidation of the
      benzylic alcohol 15 thus obtained to ketone 17 was best achieved with catalytic
      amounts of tetra-n-propylammonium perruthenate (TPAP) and N-methylmorpholine-N
      oxide (NMO) in dilute CH2Cl2 solution to avoid the formation of undue amounts of
      the unsymmetrical dimer 16. Ketone 17 was elaborated into the natural product by
      selective cleavage of the isopropyl ether with BCl3, introduction of the sulfate
      moiety with the aid of trichloroethyl chlorosulfuric acid ester, deprotection of
      all lateral methyl ether groups, and final reductive cleavage of the
      trichloroethyl ester moiety. The spectroscopic data of synthetic dictyodendrin B
      thus formed matched those of an authentic sample in all regards. Moreover, it was
      shown that global deprotection of the peripheral -OH groups in pyrrolo[2,3
      c]carbazole 13 is accompanied by spontaneous air-oxidation to form the quinone
      core of dictyodendrin C.

PMID- 16104737
TI  - A modular and efficient synthesis of functional titanocenes.
AB  - A modular synthesis of functional titanocenes featuring building blocks is
      described. The approach allows straightforward access to large numbers of
      structurally diverse titanocenes that are pertinent for catalysis, structural
      studies, and bioinorganic chemistry. Among the functional groups introduced are
      amino acids, sugars, and fluorescence labels that are attached to the
      cyclopentadienyl ligand as esters and amides.

PMID- 16104738
TI  - Rapid 1H[13C]-resolved diffusion and spin-relaxation measurements by NMR
      spectroscopy.
AB  - Hadamard-encoded heteronuclear-resolved NMR diffusion and relaxation measurements
      allow overlapping signal decays to be resolved with substantially shorter
      measuring times than are generally associated with 2D heteronuclear cross
      correlation experiments. Overall measuring time requirements can be reduced by
      approximately an order of magnitude, compared to typical 2D heteronuclear single
      quantum correlation-resolved diffusion or relaxation measurements. Specifically,
      in cases where chemical shift correlation information provides enhanced spectral
      resolution, the use of Hadamard encoding can be used to overcome uniqueness
      challenges that are associated with the analysis of concurrent dynamic processes
      and the extraction of time constants from overlapping exponential signal decays.
      This leads to substantially improved resolution of similar time constants than
      can be achieved solely through the use of post-acquisition processing techniques.
      In the ideal case of complete spectral separation of the signal decays, the usual
      constraint that time constants must be sufficiently different to resolve by
      exponential analysis can be circumvented entirely. Hadamard-based pulse sequences
      have been used to determine 1H[13C]-resolved diffusion coefficients and spin
      relaxation time constants for the chemically similar components of an aqueous
      solution of ethanol, glycerol, and poly(ethylene glycol), and a dye-containing
      block-copolymer solution, which exhibit significant spectral overlap in their 1H
      NMR spectra.

PMID- 16104739
TI  - Biosensing using porous silicon double-layer interferometers: reflective
      interferometric Fourier transform spectroscopy.
AB  - A simple, chip-based implementation of a double-beam interferometer that can
      separate biomolecules based on size and that can compensate for changes in matrix
      composition is introduced. The interferometric biosensor uses a double-layer of
      porous Si comprised of a top layer with large pores and a bottom layer with
      smaller pores. The structure is shown to provide an on-chip reference channel
      analogous to a double-beam spectrometer, but where the reference and sample
      compartments are stacked one on top of the other. The reflectivity spectrum of
      this structure displays a complicated interference pattern whose individual
      components can be resolved by fitting of the reflectivity data to a simple
      interference model or by fast Fourier transform (FFT). Shifts of the FFT peaks
      indicate biomolecule penetration into the different layers. The small molecule,
      sucrose, penetrates into both porous Si layers, whereas the large protein, bovine
      serum albumin (BSA), only enters the large pores. BSA can be detected even in a
      large (100-fold by mass) excess of sucrose from the FFT spectrum. Detection can
      be accomplished either by computing the weighted difference in the frequencies of
      two peaks or by computing the ratio of the intensities of two peaks in the FFT
      spectrum.

PMID- 16104740
TI  - Binuclear cyclopentadienylcobalt carbonyls: comparison with binuclear iron
      carbonyls.
AB  - The binuclear cyclopentadienylcobalt carbonyls Cp2Co2(CO)n (n = 3, 2, 1; Cp =
      eta5-C5H5) are studied by density functional theory using the B3LYP and BP86
      functionals. The experimentally known monobridged isomer Cp2Co2(CO)2(mu-CO) and
      the tribridged isomer Cp2Co2(mu-CO)3 of Cp2Co2(CO)3 with formal Co-Co single
      bonds are found to be similar in energy, with the precise relative energies of
      the two isomers depending on the functional chosen. For Cp2Co2(CO)2, the
      experimentally known coaxial isomer Cp2Co2(mu-CO)2 with two bridging CO groups
      and a formal Co=Co double bond (2.360 angstroms by B3LYP or 2.346 angstroms by
      BP86) is found to lie 38.2 (B3LYP) or 34.9 kcal/mol (BP86) below a perpendicular
      isomer perpendicular-Cp2Co2(CO)2. Similarly, for Cp2Co2(CO), the coaxial isomer
      Cp2Co2(mu-CO) with one bridging CO group and a formal CoCo triple bond (2.021
      angstroms by B3LYP or 2.050 angstroms by BP86) is found to lie 9.36 (B3LYP) or
      9.62 kcal/mol (BP86) below the corresponding perpendicular isomer perpendicular
      Cp2Co2(CO). This coaxial isomer Cp2Co2(mu-CO) is a possible intermediate in the
      known pyrolysis of the trimer (eta5-C5H5)3Co3(mu-CO)3 to give the tetranuclear
      complex (eta5-C5H5)4Co4(mu3-CO)2. These optimized Cp2Co2(CO)n (n = 3, 2, 1)
      structures can be compared with the corresponding Fe2(CO)6+n structures since the
      CpCo and Fe(CO)3 groups are isolobal. In general, the metal-metal bonds are 0.09
      0.22 angstroms shorter for the Cp2Co2(CO)n (n = 3, 2, 1) complexes than for the
      corresponding Fe2(CO)6+n complexes. For Fe2(CO)9, the experimentally well-known
      Fe2(CO)6(mu-CO)3 isomer is shown to be very close in energy to the unknown
      Fe2(CO)8(mu-CO) isomer, with the precise relative energies depending on the basis
      set used.

PMID- 16104741
TI  - Single d-metal atoms on F(s) and F(s+) defects of MgO(001): a theoretical study
      across the periodic table.
AB  - Single d-metal atoms on oxygen defects F(s) and F(s+) of the MgO(001) surface
      were studied theoretically. We employed an accurate density functional method
      combined with cluster models, embedded in an elastic polarizable environment, and
      we applied two gradient-corrected exchange-correlation functionals. In this way,
      we quantified how 17 metal atoms from groups 6-11 of the periodic table (Cu, Ag,
      Au; Ni, Pd, Pt; Co, Rh, Ir; Fe, Ru, Os; Mn, Re; and Cr, Mo, W) interact with
      terrace sites of MgO. We found bonding with F(s) and F(s+) defects to be in
      general stronger than that with O2- sites, except for Mn-, Re-, and Fe/F(s)
      complexes. In M/F(s) systems, electron density is accumulated on the metal center
      in a notable fashion. The binding energy on both kinds of O defects increases
      from 3d- to 4d- to 5d-atoms of a given group, at variance with the binding energy
      trend established earlier for the M/O2- complexes, 4d < 3d < 5d. Regarding the
      evolution of the binding energy along a period, group 7 atoms are slightly
      destabilized compared to their group 6 congeners in both the F(s) and F(s+)
      complexes; for later transition elements, the binding energy increases gradually
      up to group 10 and finally decreases again in group 11, most strongly on the F(s)
      site. This trend is governed by the negative charge on the adsorbed atoms. We
      discuss implications for an experimental detection of metal atoms on oxide
      supports based on computed core-level energies.

PMID- 16104742
TI  - Luminescent silole nanoparticles as chemoselective sensors for Cr(VI).
AB  - Colloidal suspensions of 3-aminopropylmethyl(tetraphenyl)silole nanoparticles can
      be used as selective chemosensors for carcinogenic chromium(VI) analyte.
      Methylhydrosilole is functionalized by hydrosilation of allylamine, and the
      colloid is prepared by the rapid addition of water to a THF solution of the
      silole. The method of detection is through electron-transfer quenching of the
      fluorescence of the silole colloid (lambda(em) = 485 nm at 360 nm excitation) by
      the analytes, with hundred parts per billion detection limits. Stern-Volmer plots
      are linear up to 10 ppm in the case of chromium, but exhibit saturation behavior
      near 5-10 ppm for arsenic. Dynamic light scattering experiments and AFM
      measurements show the particle sizes to be around 100 nm in diameter and
      dependent on solvent composition, with a particle size dispersity of +/-25%. The
      fluorescence lifetimes of the silole in solution and colloid are approximately 31
      ps and approximately 4.3 ns, respectively, while the silole has a lifetime of 6
      ns in the bulk solid. A minimum volume fraction of 80% water is necessary to
      precipitate the colloid from THF, and the luminescence continues to rise with
      higher water fractions. Colloids in a pH 7 phosphate-buffered suspension show
      both higher sensitivity and greater selectivity (100-fold) for CrO4(2-) detection
      than for other oxoanion interferents, NO3-, NO2-, SO4(2-), and ClO4-.

PMID- 16104743
TI  - Control of extremely fast competitive consecutive reactions using micromixing.
      Selective Friedel-Crafts aminoalkylation.
AB  - Friedel-Crafts reactions of aromatic and heteroaromatic compounds with an N
      acyliminium ion pool were studied. The reaction of 1,3,5-trimethylbenzene in a
      batch reactor gave rise to the selective formation of a monoalkylation product
      (69%). Presumably, the second alkylation is slower than the first alkylation
      because of the protonation of the monoalkylation product that decreases its
      reactivity. The reaction of 1,3,5-trimethoxybenzene, however, gave rise to the
      formation of both monoalkylation (37%) and dialkylation (32%) products. Disguised
      chemical selectivity due to faster reaction than mixing seems to be responsible
      for the lack of selectivity. The use of micromixing was found to be quite
      effective to solve this problem to increase the selectivity. The monoalkylation
      product was obtained in 92% yield together with a small amount of the
      dialkylation product (4%). The reaction with various aromatic and heteroaromatic
      compounds revealed that the low mono/dialkylation selectivity was observed only
      for highly reactive aromatics. In such cases, the use of micromixing was quite
      effective to improve the selectivity. On the basis of micromixing, the selective
      sequential dialkylation using two different N-acyliminium ions was achieved. CFD
      simulations using a laminar flow and finite-rate model are consistent with the
      experimental observations and clearly indicate the importance of mixing.

PMID- 16104744
TI  - Dynamics of xenon binding inside the hydrophobic cavity of pseudo-wild-type
      bacteriophage T4 lysozyme explored through xenon-based NMR spectroscopy.
AB  - Wild-type bacteriophage T4 lysozyme contains a hydrophobic cavity with binding
      properties that have been extensively studied by X-ray crystallography and NMR.
      In the present study, the monitoring of 1H chemical shift variations under xenon
      pressure enables the determination of the noble gas binding constant (K = 60.2 M(
      1)). Although the interaction site is highly localized, dipolar cross-relaxation
      effects between laser-polarized xenon and nearby protons (SPINOE) are rather
      poor. This is explained by the high value of the xenon-proton dipolar correlation
      time (0.8 ns), much longer than the previously reported values for xenon in
      medium-size proteins. This indicates that xenon is highly localized within the
      protein cavity, as confirmed by the large chemical shift difference between free
      and bound xenon. The exploitation of the xenon line width variation vs xenon
      pressure and protein concentration allows the extraction of the exchange
      correlation time between free and bound xenon. Comparison to the exchange
      experienced by protein protons indicates that the exchange between the open and
      closed conformations of T4 lysozyme is not required for xenon binding.

PMID- 16104745
TI  - The binding energy and bonding in dialane.
AB  - The binding energy of dialane, Al2H6, has been measured using mass spectrometric
      techniques to be 33 +/- 5 kcal/mol. This represents the first measurement of the
      thermochemical properties of dialane, which has only recently been observed in
      low-temperature matricies. High-level quantum mechanical calculations give a
      binding energy in agreement with the measured value. Experimental and quantum
      mechanical calculations show that dialane is chemically similar to diborane,
      B2H6, even though the bonding for these two systems shows significant
      differences.

PMID- 16104746
TI  - Nature of minor-groove binders-DNA complexes in the gas phase.
AB  - The structure of noncovalent complexes of DNA duplex with minor groove binders
      (mG-binders) has been analyzed by state of the art molecular dynamics (MD)
      simulations. More than 3.3 micros of MD trajectories (including 4 x 0.5 micros
      trajectories) were collected for the Dickerson's dodecamer bound to DAPI, Hoechst
      33258, and Netropsin. Comparison of these trajectories with control simulations
      in water allowed us to determine that the extreme dehydration and partial
      neutralization occurring during electrospray experiments does not produce the
      disruption of the DNA:mG-binder complexes or the dissociation of the two strands
      of the duplex. Irrespective of the drug and the simulation conditions the mG
      binders remains bound to the DNA near the preferential binding position in
      aqueous conditions. Large distortions appear in the two DNA strands, which
      maintain however a memory of the original DNA duplex structure in water, and a
      general helical-like conformation.

PMID- 16104747
TI  - Comparison of the ATP binding sites of protein kinases using conformationally
      diverse bisindolylmaleimides.
AB  - The conformation of a bisindolylmaleimide may be controlled by the size of a
      macrocyclic ring in which it is constrained. A range of techniques were used to
      demonstrate that the tether controls both the ratio of the two limiting
      conformers (syn and anti) in solution and the extent of conjugation between the
      maleimide and indole rings. Screening the conformationally diverse
      bisindolylmaleimides against a panel of protein kinases allowed their ATP binding
      sites to be compared using a chemical approach which, like sequence alignment,
      does not require detailed structural information. This approach lead to the
      conclusion that several AGC group protein kinases (including PKCalpha, PKCbeta,
      MSK1, p70 S6K, PDK-1, and MAPKAP-K1alpha) may be best inhibited by
      bisindolylmaleimides which adopt a compressed approximately C2-symmetric anti
      conformation; in constrast, GSK3beta may be best inhibited by
      bisindolylmaleimides whose ground state is a distorted syn conformation. It is
      concluded that PDK-1, whose structure has been determined by X-ray
      crystallography, and its mutants, may serve as particularly useful surrogates for
      the study of PKC inhibitors.

PMID- 16104748
TI  - Dynamic mechanism for the autophosphorylation of CheA histidine kinase: molecular
      dynamics simulations.
AB  - The two-component system (TCS) is an important signal transduction component for
      most bacteria. This signaling pathway is mediated by histidine kinases via
      autophosphorylation between P1 and P4 domains. Taking chemotaxis protein CheA as
      a model of TCS, the autophosphorylation mechanism of the TCS histidine kinases
      has been investigated in this study by using a computational approach integrated
      homology modeling, ligand-protein docking, protein-protein docking, and molecular
      dynamics (MD) simulations. Four nanosecond-scale MD simulations were performed on
      the free P4 domain, P4-ATP, P4-TNPATP, and P1-P4-ATP complexes, respectively.
      Upon its binding to the binding pocket of P4 with a folded conformation, ATP
      gradually extends to an open state with help from a water molecule. Meanwhile,
      ATP forms two hydrogen bonds with His413 and Lys494 at this state. Because of the
      lower energy of the folded conformations, ATP shrinks back to its folded
      conformations, leading to the rupture of the hydrogen bond between ATP and
      Lys494. Consequently, Lys494 moves away from the pocket entrance, resulting in an
      open of the ATP lid of P4. It is the open state of P4 that can bind tightly to
      P1, where the His45 of P1 occupies a favorable position for its
      autophosphorylation from ATP. This indicates that ATP is not only a phosphoryl
      group donor but also an activator for CheA phosphorylation. Accordingly, a
      mechanism of the autophosphorylation of CheA is proposed as that the ATP
      conformational switch triggers the opening of the ATP lid of P4, leading to P1
      binding tightly, and subsequently autophosphorylation from ATP to P1.

PMID- 16104749
TI  - Photoinduced nitric oxide release from nitrobenzene derivatives.
AB  - A new type of photoinduced nitric oxide (NO) donors was designed from
      nitrobenzene derivatives. Visible-light irradiation of 2,6-dimethylnitrobenzenes
      bearing extended pi-electron systems at the 4-position revealed efficient NO
      release using ESR analysis and the Griess assay. Computational study and
      ultraviolet spectrum analysis suggested that the NO-releasing activity was
      closely related to the conformation of the nitro group, the absorption intensity,
      and the length of the conjugated pi-electron system. Employing the photodependent
      cytotoxicity of compound 14 against HCT116 human colon cancer cells, it was
      demonstrated that 4-substituted-2,6-dimethylnitrobenzene analogues are useful NO
      donors for the time- and site-controlled NO treatment.

PMID- 16104750
TI  - Ribosomal synthesis of unnatural peptides.
AB  - Combinatorial libraries of non-biological polymers and drug-like peptides could
      in principle be synthesized from unnatural amino acids by exploiting the broad
      substrate specificity of the ribosome. The ribosomal synthesis of such libraries
      would allow rare functional molecules to be identified using technologies
      developed for the in vitro selection of peptides and proteins. Here, we use a
      reconstituted E. coli translation system to simultaneously re-assign 35 of the 61
      sense codons to 12 unnatural amino acid analogues. This reprogrammed genetic code
      was used to direct the synthesis of a single peptide containing 10 different
      unnatural amino acids. This system is compatible with mRNA-display, enabling the
      synthesis of unnatural peptide libraries of 10(14) unique members for the in
      vitro selection of functional unnatural molecules. We also show that the chemical
      space sampled by these libraries can be expanded using mutant aminoacyl-tRNA
      synthetases for the incorporation of additional unnatural amino acids or by the
      specific posttranslational chemical derivitization of reactive groups with small
      molecules. This system represents a first step toward a platform for the
      synthesis by enzymatic tRNA aminoacylation and ribosomal translation of cyclic
      peptides comprised of unnatural amino acids that are similar to the nonribosomal
      peptides.

PMID- 16104751
TI  - Solute-solvent interactions and chiral induction in liquid crystals.
AB  - The induction of a cholesteric phase by doping an achiral nematic liquid crystal
      with an enantiopure solute is a phenomenon that, as in all general supramolecular
      phenomena of chiral amplification, depends in a subtle way on intermolecular
      interactions. The micrometric helical deformation of the phase director in the
      cholesteric phase is generated by the interplay of anisotropy and chirality of
      probe-medium interactions. In the case of a flexible chiral dopant, the solvent
      can influence the twisting power in two ways, difficult to disentangle: it is
      responsible for the solute orientational order, an essential ingredient for the
      emergence of phase chirality; but also it can affect the dopant conformational
      distribution and then the chirality of the structures present in the solution. In
      this work we have investigated methyl phenyl sulfoxide, a flexible, chiral
      molecule that, when dissolved in different nematics, can produce cholesteric
      phases of opposite handedness. This peculiar, intriguing sensitivity to the
      environment makes MPS a suitable probe for a thorough investigation of the
      effects of solute-solvent interactions on chiral induction in liquid crystals.
      NMR experiments in various nematic solvents have been performed in addition to
      twisting power measurements. From the analysis of partially averaged 1H-1H and
      13C-1H dipolar couplings, the effects of solvent on solute conformation and
      orientational order are disentangled, and this information is combined with the
      modeling of the chirality of intermolecular interactions, within a molecular
      field theory. The integration of different techniques allows an unprecedented
      insight into the role of solvent in mediating the chirality transfer from
      molecule to phase.

PMID- 16104752
TI  - Peroxidase-catalyzed in situ polymerization of surface orientated caffeic acid.
AB  - Nanoscale surface patterning and polymerization of caffeic acid on 4
      aminothiophenol-functionalized gold surfaces has been demonstrated with dip pen
      nanolithography (DPN). The diphenolic moiety of caffeic acid can be polymerized
      by biocatalysis with laccase or horseradish peroxidase. In the present study, the
      DPN patterned features were polymerized in situ through the use of the
      peroxidase. Using samples prepared by DPN, microcontact printing, and adsorption
      on macroscopic substrates, the products were characterized by electrostatic force
      microscopy (EFM), MALDI-TOF, X-ray photoelectron spectroscopy (XPS), UV-vis, and
      FT-IR. The in situ surface polymerization resulted in the formation of a quinone
      structure, while the phenyl ester formed in bulk polymerization reactions was not
      detected. A different coupling site was observed when comparing the polymers
      obtained from solution (bulk) vs the surface DPN reactions. The structural
      differences were attributed to surface-induced pre-organization and orientation
      of the monomers prior to the enzymatic polymerization step. The results of this
      study expand the application of DPN technology to surface modification and
      surface chemistry reactions wherein stereo-regularity and regioselectivity can be
      exploited.

PMID- 16104753
TI  - Oxygenated hydrocarbon ionic surfactants exhibit CO2 solubility.
AB  - Several oxygenated hydrocarbons, including acetylated sugars, poly(propylene
      glycol), and oligo(vinyl acetate), have been used to generate CO2-soluble ionic
      surfactants. Surfactants with vinyl acetate tails yielded the most promising
      results, exhibiting levels of CO2 solubility comparable to those associated with
      fluorinated ionic surfactants. For example, a sodium sulfate with single,
      oligomeric vinyl acetate (VAc) tails consisting of 10 VAc repeat units was 7 wt %
      soluble in CO2 at 25 degrees C and 48 MPa. Upon introduction of water to these
      systems, only surfactants with the oligomeric vinyl acetate tails exhibited
      spectroscopic evidence of a polar environment that was capable of solubilizing
      the methyl orange into the CO2-rich phase. For example, a single-phase solution
      of CO2, 0.15 wt % sodium bis(vinyl acetate)8 sulfosuccinate, and water, at water
      loading (W) values ranging from 10 to 40 at 25 degrees C and 34.5 MPa, exhibited
      a methyl orange peak at 423 nm. This result indicated that the core of a reverse
      micelle provided a microenvironment with a polarity similar to that of methanol.
      Quantum chemical calculations indicate that the acetylated sugars may be too
      hydrophilic to readily form reverse micelles, whereas the VAc-based surfactants
      appear to have the correct balance of hydrophilic and hydrophobic forces
      necessary to form reverse micelles.

PMID- 16104754
TI  - Synthesis and energy-transfer properties of hydrogen-bonded oligofluorenes.
AB  - A set of fluorene oligomers has been synthesized by stepwise palladium-catalyzed
      (Suzuki) couplings of fluorene monomers. Ureidopyrimidinones (UPy), functional
      groups that can dimerize via quadruple hydrogen bonds, were attached to both ends
      of the oligofluorenes. The resulting bis-UPy-terminated oligomers self-assemble
      into supramolecular chain polymers. For comparison, oligofluorenes of the same
      oligomer lengths but without terminal hydrogen-bonding groups were synthesized.
      Chains of hydrogen-bonded fluorenes can be simply endcapped by a variety of chain
      stoppers, molecules that have one UPy group. In this manner, we have endcapped
      the hydrogen-bonded fluorene chains with either oligo(p-phenylenevinylene) or
      perylene bisimide. Energy-transfer experiments in solution and the solid state
      demonstrate that oligofluorenes can donate energy to a variety of energy
      acceptors, but that this energy transfer occurs most effectively when the donor
      fluorene is hydrogen-bonded to the acceptor.

PMID- 16104755
TI  - End-cap effects on vibrational structures of finite-length carbon nanotubes.
AB  - Vibrational structures of C60-related finite-length nanotubes, C(40+20n) and
      C(42+18n) (1 < or = n < or = 4), in which n is, respectively, the number of
      cyclic cis- and trans-polyene chains inserted between fullerene hemispheres, are
      analyzed from density functional theory (DFT) calculations. To illuminate the end
      cap effects on their vibrational structures, the corresponding tubes terminated
      by H atoms C(20n)H20 and C(18n)H18 (1 < or = n < or = 5) are also investigated.
      DFT calculations show a broad range of vibrational frequencies for the finite
      size nanotubes: high-frequency modes (1100-1600 cm(-1)) containing oscillations
      along tangential directions (tangential modes), medium-frequency modes (700-850
      cm(-1)) whose oscillations are located on the edges or end caps, and low
      frequency modes (300-600 cm(-1)) involving oscillations along the radial
      directions (radial modes). Broadening of the calculated frequencies is due to the
      number of nodes in the standing waves of normal modes in the finite-size tubes.
      In the capped tubes, calculated vibrational frequencies are insensitive to the
      number of chains (n), whereas in the uncapped tubes, most vibrational frequencies
      change significantly with an increase in tube length. The discrepancy in the size
      dependency is reasonably understood by their C-C bonding networks; the capped
      tubes have similar bond-length alternation patterns within the polyene chains
      irrespective of n, whereas the uncapped tubes have various bond-deformation
      patterns. Thus, DFT calculations illuminate that the edge effects have strong
      impacts on the vibrational frequencies in the finite-size nanotubes.

PMID- 16104756
TI  - Tailoring the optical property by a three-dimensional epitaxial heterostructure:
      a case of ZnO/SnO2.
AB  - Epitaxial growth, as a best strategy to attain a heterostructure with a well
      defined and clean interface, usually takes place on a planar substrate. In this
      paper, using a ZnO/SnO2 core-shell heterostructure as an example, we demonstrate
      the possibility of establishing a three-dimensional epitaxial interface between
      two materials with different crystal systems for the first time and show possible
      tailoring optical properties by building the heteroepitaxial crystal interface.
      The characterization results of element mapping, high-resolution transmission
      electron microscopy, and selected area electric diffraction reveal that the as
      prepared ZnO/SnO2 heterostructure has a tetrapod-like ZnO core and a SnO2 shell
      with 15-30 nm, and their special epitaxial relation is (010)SnO2//(010)ZnO and
      [100]SnO2//[0001]ZnO. Such three-dimensional epitaxy between the ZnO core and
      SnO2 shell is quite different from the usual planar epitaxy or three-dimensional
      epitaxy between materials having the same crystal structure. A rational model of
      such complicated epitaxy has been proposed through investigating the certain
      structural comparability between the wurtzite ZnO and rutile SnO2 crystals. The
      as-prepared T-ZnO/SnO2 epitaxial heterostructure exhibits unique luminescence
      properties in contrast with individual tetrapod ZnO and SnO2 nanostructures, in
      which the epitaxial interface induces new luminescence properties. This result
      may inspire great interest in exploring other complicated epitaxy systems and
      their potential applications in laser, gas sensor, solar energy conversion, photo
      catalysis, and nanodevices in the future.

PMID- 16104757
TI  - (EDT-TTF-CONH2)6[Re6Se8(CN)6], a metallic Kagome-type organic-inorganic hybrid
      compound: electronic instability, molecular motion, and charge localization.
AB  - (EDT-TTF-CONH2)6[Re6Se8(CN)6], space group R, was prepared by
      electrocrystallization from the primary amide-functionalized
      ethylenedithiotetrathiafulvalene, EDT-TTF-CONH2 (E(1/2)1 = 0.49 V vs SCE in
      CH3CN), and the molecular cluster tetraanion, [Re6Se8(CN)6]4- (E(1/2) = 0.33 V vs
      SCE in CH3CN), equipped with hydrogen bond donor and hydrogen bond acceptor
      functionalities, respectively. Its Kagome topology is unprecedented for any TTF
      based materials. The metallic state observed at room temperature has a strong two
      dimensional character, in coherence with the Kagome lattice symmetry, and the
      presence of minute amounts of [Re6Se8(CN)6](3-)* identified by electron spin
      spectroscopy. A structural instability toward a distorted form of the Kagome
      topology of lesser symmetry is observed at ca. 180 K. The low-temperature
      structure is associated with a localized, electrically insulating electronic
      ground state and its magnetic susceptibility accounted for by a model of uniform
      chains of localized S = 1/2 spins in agreement with the 100 K triclinic crystal
      structure and band structure calculations. A sliding motion, within one out of
      the three (EDT-TTF-CONH2)2 dimers coupled to the [Re6Se8(CN6)(3-)*]/[Re6Se8(CN6)4
      ] proportion at any temperature, and the electronic ground state of the organic
      inorganic hybrid material are analyzed on the basis of ESR, dc conductivity, 1H
      spin-lattice relaxation, and static susceptibility data which qualify a Mott
      localization in [EDT-TTF-CONH2]6[Re6Se8(CN)6]. The coupling between the metal
      insulator transition and a structural transition allows for the lifting of a
      degeneracy due to the ternary axis in the high temperature, strongly correlated
      metallic phase which, in turn, leads to Heisenberg chains at low temperature.

PMID- 16104758
TI  - Cell penetrating agents based on a polyproline helix scaffold.
AB  - Cell penetrating agents were designed and synthesized that introduce cationic and
      hydrophobic moieties along the backbone of a polyproline helix (PPII) in an
      amphiphilic manner. The CD profile has the features that are expected for a PPII
      helix, demonstrating that the addition of these groups had little effect on the
      backbone structure. Dramatic increases in uptake were found with MCF-7 cells when
      up to six guanidinium groups were positioned on the polyproline helix, whereas
      only modest increases in cellular uptake were observed with the amine-containing
      polyproline compounds as compared to their flexible counterparts. Amphiphilicity
      played a key role in the enhanced cell translocation, as scrambled versions of
      the designed agents, with hydrophobic and cationic groups on all faces of the
      helix, were only as effective as their flexible peptide counterparts.
      Interestingly, the most potent agent, P11LRR, demonstrated almost an order of
      magnitude more efficient cellular uptake as compared to that of the well-studied
      Tat peptide, with minimal cytotoxicity.

PMID- 16104759
TI  - Combinatorial synthesis of MUC1 glycopeptides: polymer blotting facilitates
      chemical and enzymatic synthesis of highly complicated mucin glycopeptides.
AB  - The chemoselective polymer blotting method allows for rapid and efficient
      synthesis of glycopeptides based on a "catch and release" strategy between solid
      phase and water-soluble polymer supports. We have developed a heterobifunctional
      linker sensitive to glutamic acid specific protease (BLase). The general
      procedure consists of five steps, namely (i) the solid-phase synthesis of
      glycopeptide containing BLase sensitive linker, (ii) subsequent deprotections and
      the release of the glycopeptide from the resin, (iii) chemoselective blotting of
      the glycopeptide intermediates in the presence of water-soluble polymers with
      oxylamino functional groups, (iv) sugar elongations using glycosyltransferases,
      and (v) the release of target glycopeptides from the polymer platform by
      selective BLase promoted hydrolysis. The combined use of the solid-phase chemical
      syntheses of peptides and the enzymatic syntheses of carbohydrates on water
      soluble polymers would greatly contribute to the production of complicated
      glycopeptide libraries, thereby enhancing applicative research. We report here a
      high-throughput synthetic system for the various types of MUC1 glycopeptides
      exhibiting a variety of sugar moieties. It is our belief that this concept will
      become part of the entrenched repertoire for the synthesis of biologically
      important glycopeptides on the basis of glycosyltransferase reactions in
      automated and combinatorial syntheses.

PMID- 16104760
TI  - Conformationally induced electrostatic stabilization of persulfoxides: a new
      suggestion for inhibition of physical quenching of singlet oxygen by remote
      functional groups.
AB  - 1,5-Dithiacyclooctane is shown to chemically react more efficiently and to remove
      singlet oxygen from solution more rapidly than either thiane or 1,4-dithiane.
      These unusual characteristics of the 1,5-dithiacyclooctane reaction were explored
      using ab initio quantum chemical methods. A large number of persulfoxides,
      thiadioxiranes, and hydroperoxy sulfonium ylides were located and their
      structures analyzed. The unusual efficiency of the reaction was attributed to a
      conformational change that electrostatically stabilized the persulfoxide and
      increased the potential energy barrier for physical quenching.

PMID- 16104761
TI  - Van der Waals interactions dominate ligand-protein association in a protein
      binding site occluded from solvent water.
AB  - In the present study we examine the enthalpy of binding of 2-methoxy-3
      isobutylpyrazine (IBMP) to the mouse major urinary protein (MUP), using a
      combination of isothermal titration calorimetry (ITC), NMR, X-ray
      crystallography, all-atom molecular dynamics simulations, and site-directed
      mutagenesis. Global thermodynamics data derived from ITC indicate that binding is
      driven by favorable enthalpic contributions, rather than a classical entropy
      driven signature that might be expected given that the binding pocket of MUP-1 is
      very hydrophobic. The only ligand-protein hydrogen bond is formed between the
      side-chain hydroxyl of Tyr120 and the ring nitrogen of the ligand in the wild
      type protein. ITC measurements on the binding of IBMP to the Y120F mutant
      demonstrate a reduced enthalpy of binding, but nonetheless binding is still
      enthalpy dominated. A combination of solvent isotopic substitution ITC
      measurements and all-atom molecular dynamics simulations with explicit inclusion
      of solvent water suggests that solvation is not a major contributor to the
      overall binding enthalpy. Moreover, hydrogen/deuterium exchange measurements
      suggest that there is no significant contribution to the enthalpy of binding
      derived from "tightening" of the protein structure. Data are consistent with
      binding thermodynamics dominated by favorable dispersion interactions, arising
      from the inequality of solvent-solute dispersion interactions before complexation
      versus solute-solute dispersion interactions after complexation, by virtue of
      poor solvation of the binding pocket.

PMID- 16104762
TI  - Cooperation between artificial receptors and supramolecular hydrogels for sensing
      and discriminating phosphate derivatives.
AB  - This study has successfully demonstrated that the cooperative action of
      artificial receptors with semi-wet supramolecular hydrogels may produce a unique
      and efficient molecular recognition device not only for the simple sensing of
      phosphate derivatives, but also for discriminating among phosphate derivatives.
      We directly observed by confocal laser scanning microscopy that fluorescent
      artificial receptors can dynamically change the location between the aqueous
      cavity and the hydrophobic fibers upon guest-binding under semi-wet conditions
      provided by the supramolecular hydrogel. On the basis of such a guest-dependent
      dynamic redistribution of the receptor molecules, a sophisticated means for
      molecular recognition of phosphate derivatives can be rationally designed in the
      hydrogel matrix. That is, the elaborate utilization of the hydrophobic fibrous
      domains, as well as the water-rich hydrophilic cavities, enables us to establish
      three distinct signal transduction modes for phosphate sensing: the use of (i) a
      photoinduced electron transfer type of chemosensor, (ii) an environmentally
      sensitive probe, and (iii) an artificial receptor displaying a fluorescence
      resonance energy transfer type of fluorescent signal change. Thus, one can
      selectively sense and discriminate the various phosphate derivatives, such as
      phosphate, phospho-tyrosine, phenyl phosphate, and adenosine triphosphate, using
      a fluorescence wavelength shift and a seesaw type of ratiometric fluorescence
      change, as well as a simple fluorescence intensity change. It is also shown that
      an array of the miniaturized hydrogel is promising for the rapid and high
      throughput sensing of these phosphate derivatives.

PMID- 16104763
TI  - Conformationally gated switching between superexchange and hopping within oligo-p
      phenylene-based molecular wires.
AB  - We observe well-defined regions of superexchange and thermally activated hopping
      in the temperature dependence of charge recombination (CR) in a series of donor
      bridge-acceptor (D-B-A) systems, where D = phenothiazine (PTZ), B = p-phenylene
      (Ph(n)), n = 1-4, and A = perylene-3,4:9,10-bis(dicarboximide) (PDI). A fit to
      the thermally activated CR rates of the n = 3 and n = 4 compounds yields
      activation barriers of 1290 and 2030 cm(-1), respectively, which match closely
      with theoretically predicted and experimentally observed barriers for the
      planarization of terphenyl and quaterphenyl. Negative activation of CR in the
      temperature regions dominated by superexchange charge transport is the result of
      a fast conformational equilibrium that increasingly depopulates the reactive
      state for CR as temperature is increased. The temperature dependence of the
      effective donor-acceptor superexchange coupling, V(DA), measured using magnetic
      field effects on the efficiency of the charge recombination process, shows that
      CR occurs out of the conformation with lower V(DA) via the energetically favored
      triplet pathway.

PMID- 16104765
TI  - Reaction pathways leading to arylene ethynylene macrocycles via alkyne
      metathesis.
AB  - Mechanistic studies on the direct formation of arylene ethynylene macrocycles via
      alkyne metathesis catalyzed by a molybdenum complex are reported. Gel permeation
      chromatography (GPC) and matrix-assisted laser desorption ionization (MALDI) mass
      spectrometry on the products from metathesis of monomer 1 show the initial
      formation of linear oligomers and large macrocycles (n > 6), followed by their
      transformation into the thermodynamically most stable product distribution-mainly
      the cyclic hexamer. Variable temperature and scrambling experiments reveal the
      reversibility of macrocycle formation. Nearly identical product distributions are
      observed from the cross metathesis of hexacycle 2 with diphenylacetylene and from
      the metathesis of bis(phenylethynyl) substituted monomer 4, demonstrating that
      macrocycle formation is thermodynamically rather than kinetically controlled. The
      metathesis byproduct, 3-hexyne, is shown to inhibit the catalyst. It is suggested
      that the relative metathesis rates of dialkylalkynes versus diarylalkynes trap
      the catalyst in a nonproductive manifold, rendering it unavailable for the
      productive metathesis of aryl alkylalkyne substrates. This finding indicates that
      dialkyl-substituted alkyne byproducts should be avoided (or efficiently removed)
      if the metatheses of aryl substrates, especially those with electron-withdrawing
      groups, are to proceed to high conversion.

PMID- 16104764
TI  - Phosphorescent oxygen sensor with dendritic protection and two-photon absorbing
      antenna.
AB  - Imaging oxygen in 3D with submicron spatial resolution can be made possible by
      combining phosphorescence quenching technique with multiphoton laser scanning
      microscopy. Because Pt and Pd porphyrin-based phosphorescent dyes, traditionally
      used as phosphors in biological oxygen measurements, exhibit extremely low two
      photon absorption (2PA) cross-sections, we designed a nanosensor for oxygen, in
      which a 2P absorbing antenna is coupled to a metalloporphyrin core via
      intramolecular energy transfer (ET) with the purpose of amplifying the 2PA
      induced phosphorescence of the metalloporphyrin. The central component of the
      device is a polyfunctionalized Pt porphyrin, whose triplet state emission at
      ambient temperatures is strong, occurs in the near infrared and is sensitive to
      O2. The 2PA chromophores are chosen in such a way that their absorption is
      maximal in the near infrared (NIR) window of tissue (e.g., 700-900 nm), while
      their fluorescence is overlapped with the absorption band(s) of the core
      metalloporphyrin, ensuring an efficient antenna-core resonance ET. The
      metalloporphyrin-antenna construct is embedded inside the protecting dendritic
      jacket, which isolates the core from interactions with biological macromolecules,
      controls diffusion of oxygen and makes the entire sensor water-soluble. Several
      Pt porphyrin-coumarin based sensors were synthesized and their photophyics
      studied to evaluate the proposed design.

PMID- 16104766
TI  - Oxidation resistant germanium nanowires: bulk synthesis, long chain alkanethiol
      functionalization, and Langmuir-Blodgett assembly.
AB  - A simple method is developed to synthesize gram quantities of uniform Ge
      nanowires (GeNWs) by chemical vapor deposition on preformed, monodispersed seed
      particles loaded onto a high surface area silica support. Various chemical
      functionalization schemes are investigated to passivate the GeNW surfaces using
      alkanethiols and alkyl Grignard reactions. The stability of functionalization
      against oxidation of germanium for various alkyl chain lengths is elucidated by X
      ray photoelectron spectroscopy. Among all schemes tested, long chain alkanethiols
      (> or = C12) are found to impart the most stable GeNW passivation against
      oxidation upon extended exposure to ambient air. Further, the chemically
      functionalized oxidation-resistant nanowires are soluble in organic solvents and
      can be readily assembled into close-packed Langmuir-Blodgett films potentially
      useful for future high performance electronic devices.

PMID- 16104767
TI  - In situ simultaneous analysis of polyacetylenes, carotenoids and polysaccharides
      in carrot roots.
AB  - This paper presents an approach to simultaneously analyze polyacetylenes,
      carotenoids, and polysaccharides in carrot (Daucus carota L.) roots by means of
      Raman spectroscopy. The components were measured in situ in the plant tissue
      without any preliminary sample preparation. The analysis is based on the
      intensive and characteristic key bands observed in the Raman spectrum of carrot
      root. The molecular structures of the main carrot polyacetylenes, falcarinol and
      falcarindiol, are similar, but their Raman spectra exhibit specific differences
      demonstrated by the shift of their -C[triple bond]C- mode from 2258 to 2252 cm(
      )(1), respectively. Carotenoids can be identified by -C=C- stretching vibrations
      (about 1520 and 1155 cm(-)(1)) of the conjugated system of their polyene chain,
      whereas the characteristic Raman band at 478 cm(-)(1) indicates the skeletal
      vibration mode of starch molecule. The other polysaccharide, pectin, can be
      identified by the characteristic band at 854 cm(-)(1), which is due to the -C-O-C
      skeletal mode of alpha-anomer carbohydrates. The Raman mapping technique applied
      here has revealed detailed information regarding the relative distribution of
      polyacetylenes, carotenoids, starch, and pectin in the investigated plant
      tissues. The distribution of these components varies among various carrot
      cultivars, and especially a significant difference can be seen between cultivated
      carrot and the wild relative D. carota ssp. maritimus.

PMID- 16104768
TI  - Rapid peroxyl radical scavenging capacity (PSC) assay for assessing both
      hydrophilic and lipophilic antioxidants.
AB  - This paper reports a simple, rapid, and sensitive assay for assessing peroxyl
      radical scavenging capacity (PSC) of both hydrophilic and lipophilic antioxidant
      compounds and food extracts. The assay is based on the degree of inhibition of
      dichlorofluorescin oxidation by antioxidants that scavenge peroxyl radicals,
      generated from thermal degradation of 2,2'-azobis(amidinopropane). For
      hydrophilic antioxidant activity, the dose required to cause a 50% inhibition of
      the reaction (EC(50)) ranged from 2.41 +/- 0.02 (EGCG) to 21.26 +/- 0.38 microM
      (ferulic acid). EC(50) values for the hydrophilic antioxidant activity of food
      extracts ranged from 309.2 +/- 3.63 (apple) to 3345.1 +/- 151.5 micromol of
      vitamin C equiv/100 g for wheat bran. The EC(50) values for lipophilic
      antioxidant activity were 1.58 +/- 0.11 (Trolox), 4.35 +/- 0.43 (alpha
      tocopherol), 18.94 +/- 0.38 (BHA), and 182.69 +/- 13.7 microM (BHT). Whole grain
      lipophilic antioxidant activity ranged from 3.49 +/- 0.57 (wheat) to 8.79 +/-
      1.98 micromol of alpha-tocopherol equiv/100 g of rice. Hydrophilic antioxidant
      activity contributed >98% of the total antioxidant activity (hydrophilic plus
      lipophilic) of whole grains tested. The PSC assay was accurate (86-108%
      recovery), precise (0.12-11% CV), and reproducible (12% RSD) and produced results
      comparable to those of similar published assays. The PSC assay can be routinely
      used to analyze or screen both hydrophilic and lipophilic antioxidants or food
      extracts and will be a valuable alternative biomarker for future epidemiological
      studies of chronic diseases.

PMID- 16104769
TI  - Classification of modified starches by fourier transform infrared spectroscopy
      using support vector machines.
AB  - The aim of this study was to compare the performance of different supervised
      discrimination methods based on IR data for the classification of starches
      according to the type of chemical modification undergone. The goal of the
      supervised classification methods is to develop classification rules.
      Representative samples of each group (known beforehand) were available, from
      which the relevant characteristics (chemical modification) were known. On the
      basis of a training data set, classification rules are determined, which can then
      be applied to classify new (unknown) samples.

PMID- 16104770
TI  - Simple assay for analyzing five microcystins and nodularin in fish muscle tissue:
      hot water extraction followed by liquid chromatography-tandem mass spectrometry.
AB  - A simple, specific, and sensitive procedure for determining six cyanotoxins, that
      is, microcystins RR, LR, YR, LA, and LW and nodularin, in fish muscle tissue is
      presented. This method is based on the matrix solid-phase dispersion technique
      with heated water as extractant followed by liquid chromatography (LC)-tandem
      mass spectrometry (MS) equipped with an electrospray ion source. Target compounds
      were extracted from tissue by 4 mL of water acidified to pH 2 and heated at 80
      degrees C. After acidification and filtration, 0.2 mL of the aqueous extract was
      injected in the LC column. MS data acquisition was performed in the multireaction
      monitoring mode, with at least two precursor ion > product ion transitions
      selected for each target compound. Analyte recovery ranged between 61 and 82% and
      was not substantially affected by either the analyte concentrations or the type
      of fish. The nonexcellent recovery of some of the microcystins was traced to
      binding of these compounds to protein phosphatases in fish tissue occurring
      during sample treatment. The existence of covalently bound microcystins in fish
      has been evidenced by several studies. Compared to an older sample preparation
      procedure, this one extracted larger amounts of the analytes in a simpler and
      much more rapid way. On the basis of a signal-to-noise ratio of 10, limits of
      quantification were estimated to range between 1.6 and 4.0 ng/g. The effects of
      temperature and volume of the extractant on the analyte recovery were studied.

PMID- 16104771
TI  - Simple and rapid method for the differentiation of Lens culinaris Medik. from
      false lentil species.
AB  - The practice of using both common vetch (Vicia sativa L.) and single-flower vetch
      (Vicia articulata Hornem.) seeds as food or feed is encouraged by the very high
      resemblance of their seeds with those of small-seeded lentil cultivars. Among the
      Vicieae, antinutritional and toxic factors are particularly important, because
      many species, containing high levels of these compounds, are not safe. A simple
      and fast capillary electrophoresis (CE) method was proposed for the
      differentiation of lentil cultivars from false lentil species (i.e., single-flour
      vetch and common vetch). Proteins were extracted from defatted milled seeds with
      an alcoholic/saline solution. Extracts were separated in an uncoated fused-silica
      capillary with iminodiacetic acid (IDA) isolectric buffer containing 0.05%
      hydroxypropylmethylcellulose (HPMC) and 20% acetonitrile. The presented method is
      useful also for the detection of contamination of whole or split seeds of lentil
      by vetch species. With respect to alternative techniques, such as DNA-based
      markers or thin-layer chromatography (TLC), CE has the advantages of being less
      expensive, faster, and fully automated.

PMID- 16104772
TI  - Simple saponification method for the quantitative determination of carotenoids in
      green vegetables.
AB  - A simple, reliable, and gentle saponification method for the quantitative
      determination of carotenoids in green vegetables was developed. The method
      involves an extraction procedure with acetone and the selective removal of the
      chlorophylls and esterified fatty acids from the organic phase using a strongly
      basic resin (Ambersep 900 OH). Extracts from common green vegetables (beans,
      broccoli, green bell pepper, chive, lettuce, parsley, peas, and spinach) were
      analyzed by high-performance liquid chromatography (HPLC) for their content of
      major carotenoids before and after action of Ambersep 900 OH. The mean recovery
      percentages for most carotenoids [(all-E)-violaxanthin, (all-E)-lutein epoxide,
      (all-E)-lutein, neolutein A, and (all-E)-beta-carotene] after saponification of
      the vegetable extracts with Ambersep 900 OH were close to 100% (99-104%), while
      the mean recovery percentages of (9'Z)-neoxanthin increased to 119% and that of
      (all-E)-neoxanthin and neolutein B decreased to 90% and 72%, respectively.

PMID- 16104773
TI  - Analysis of 2-alkylcyclobutanones with accelerated solvent extraction to detect
      irradiated meat and fish.
AB  - A new analytical procedure has been developed to analyze 2-alkylcyclobutanones to
      detect gamma-ray-irradiated fat-containing foodstuffs. Samples were extracted
      with an accelerated solvent extraction system via hot and pressurized ethyl
      acetate in cells. A large amount of fat in the extract was precipitated and
      removed with filtration by standing at -20 degrees C after the addition of
      acetonitrile. The extract was further cleaned with a 1 g silica gel mini column,
      and the radiolytic compounds of 2-docecylcyclobutanone (2-DCB) and 2
      tetradecylcyclobutanone (2-TCB) were determined with gas chromatography with mass
      spectrometry (GC/MS). Sample preparation time before GC/MS was 7-8 h. At first,
      the procedure was evaluated with a recovery test in eight samples spiked with 2
      DCB and 2-TCB at 20 ng/g, resulting in 70-105% recoveries with mostly less than
      10% relative standard deviations. The procedure was further evaluated with beef,
      pork, chicken, and salmon samples irradiated with gamma-rays from 0.7 to 7.0 kGy
      at -19 degrees C. Both 2-DCB and 2-TCB in most samples were detected with good
      dose-response relations at all doses, while salmon was detected more than 2 kGy
      irradiation. The amounts of 2-alkylcyclobutanones produced reflected precursor
      fatty acids levels in samples, especially for the combination of 2-TCB and
      stearic acid. The results indicated that the production rate of 2-TCB to stearic
      acid was more obvious than that of 2-DCB to palmitic acid in frozen samples with
      gamma-ray irradiation.

PMID- 16104774
TI  - Development of time-resolved chemiluminescence for the determination of antu in
      river water, wheat, barley, and oat grain samples.
AB  - A novel chemiluminescence method for the determination of antu has been developed
      based on the reaction between potassium permanganate in acid medium with this rat
      poison in the presence of formaldehyde as an emission enhancer. The main feature
      of the system used is that the recording of the whole chemiluminescence intensity
      vs-time profiles can be obtained, using the stopped-flow technique in a
      continuous-flow system. This enables the use of three quantitative parameters
      adjustable via software settings, one of them a typically kinetic parameter, such
      as rate of the light-decay reaction, and the others conventional parameters, such
      as maximum emission intensity and total emission area, which are proportional to
      the analyte concentration. The optimum chemical conditions for the
      chemiluminescence emission were investigated. The effect of common emission
      enhancers, such as formic acid, formaldehyde, glutaraldehyde, acetaldehyde,
      quinine, fluorescein, rhodamine B, and rhodamine 6G, was studied. The parameters
      selected were sulfuric acid 4.0 mol L(-)(1), permanganate 0.1 mmol L(-)(1), and
      formaldehyde 1.0 mol L(-)(1). The calibration graphs obtained with each one of
      the measurement parameters were linear for the concentration range from 0.05 to
      3.00 microg mL(-)(1). The detection limits ranged from 0.005 to 0.010 microg mL(
      )(1), and RSD values (n = 10) of 0.99-1.79% at a 0.30 microg mL(-)(1)
      concentration level and 1.71-2.22% at a 1.0 microg mL(-)(1) concentration level
      were obtained. The present chemiluminescence procedures were applied to the
      determination of antu in different kinds of samples, such as river water, wheat,
      barley, and oat grain samples. Recovery values not significantly different from
      the spiked amount were found for these determinations.

PMID- 16104775
TI  - Direct and combined methods for the determination of chromium, copper, and nickel
      in honey by electrothermal atomic absorption spectroscopy.
AB  - In the present work, direct methods for the determination of chromium, copper,
      and nickel in honey by electrothermal atomic absorption spectroscopy were
      developed using experimental design as an optimization tool. Once the optimum
      conditions for the individual methods were established, a direct method for the
      combined determination of the three elements was optimized using the response
      surface tool. Palladium was used as chemical modifier in all cases. Honey was
      diluted in water, hydrogen peroxide, and nitric acid. Triton X-100 was added to
      minimize the matrix effect and the viscosity of the sample. The RSD (better than
      10%) and the analytical recovery (98-103%) were acceptable for all of the
      developed methods. Calibration graphs were used in the four methods to determine
      the concentration of the analytes in the sample. The detection limits of the
      combined method (0.21, 0.35, and 0.37 microg L(-)(1) for Cr, Cu, and Ni,
      respectively) were similar to those obtained for the individual methods (LOD =
      0.17, 0.21, 0.33 microg L(-)(1) for Cr, Cu, and Ni, respectively). The direct
      combined proposed method has been applied to the determination of chromium,
      copper, and nickel content in representative honey samples from Galicia
      (northwestern Spain). The concentrations found in the analyzed samples were in
      the range of (5.75 +/- 0.64)-(26.4 +/- 0.38) ng g(-)(1) of Cr, (79 +/- 7.8)-(2049
      +/- 80) ng g(-)(1) of Cu, and (12.6 +/- 1.36)-(172 +/- 6.88) ng g(-)(1) of Ni.

PMID- 16104776
TI  - A universal HPLC method for the determination of phenolic acids in compound
      herbal medicines.
AB  - A universal method to separate and quantify 13 phenolic acids (gallic acid,
      chlorogenic acid, gentsic acid, vanillic acid, caffeic acid, syringic acid,
      sinapic acid, p-coumaric acid, ferulic acid, anisic acid, rosmarinic acid,
      salicylic acid, and cinnamic acid) in some compound herbal medicines was
      established by liquid chromatographic (HPLC). On an Agela XBP-C18 (5 microm, 4.6
      mm x 150 mm) column, a multistep binary gradient elution program and a simplified
      sample pretreatment approach were used in the experiment. For all of the phenolic
      acids, detection limits ranged around 0.01 mg/L. Linear ranges of higher than 2
      orders of magnitude were obtained with a correlation coefficient of 0.9991 to 1.
      Repeatability was 0.39-2.24% (relative standard deviation, RSD) for intraday,
      1.17-3.96% (RSD) for interday, and 0.14-5.33% (RSD) for drug sample analysis.
      Recovery, tested by a standard addition method, ranged from 83.3% to 104.9% for
      various trace phenolic acids.

PMID- 16104777
TI  - Biomimetic extraction of Bacillus thuringiensis insecticidal crystal proteins
      from soil based on invertebrate gut fluid chemistry.
AB  - Quantitative monitoring of Bacillus thuringiensis (Bt) insecticidal crystal
      proteins in soil has been hampered by the lack of efficient extraction/detection
      methods. A novel approach for simple and effective Bt protein extraction was
      explored by evaluating extraction solutions from invertebrate gut fluids. Marine
      worm gut fluids were identified as promising for extracting Bt protein from soil.
      An artificial gut fluid based on these marine worm gut fluids was developed using
      commercially available chemicals and was evaluated for its ability to extract Bt
      proteins from soil. On the basis of experiments with Cry1 proteins, the
      artificial gut fluid in combination with ELISA was highly effective for protein
      extraction and analysis in a variety of soil types and was well-correlated with
      bioassay results. Coupling of immunoassay with this extraction method provides,
      for the first time, an efficient, accurate, and quantitative assay for routine
      measurement of Bt protein residues in soil.

PMID- 16104778
TI  - Development of a novel and automated fluorescent immunoassay for the analysis of
      beta-lactam antibiotics.
AB  - An automated immunosensor for the rapid and sensitive analysis of penicillin type
      beta-lactam antibiotics has been developed and optimized. An immunogen was
      prepared by coupling the common structure of the penicillanic beta-lactam
      antibiotics, i.e., 6-aminopenicillanic acid to keyhole limpet hemocyanin.
      Polyclonal antibodies raised in rabbits after immunization with this conjugate
      have been applied for the development of a competitive fluoroimmunoassay (FIA),
      using a novel fluorescent penicillin {[2S,5R,6R]-3,3-dimethyl-7-oxo-6-[(pyren
      1ylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxilic acid, PAAP} as
      the tracer and penicillin G as the reference antibiotic. Protein A/G covalently
      bound to an azlactone-activated polymeric support was used for the orientated
      capture of the antibody-antigen immunocomplexes. Upon desorption from the
      immunosupport, the emission signal generated by the PAAP-Ab complexes is related
      to the antibiotic concentration in the sample. The 50% binding inhibition
      concentration of penicillin G standard curves was at 30 ng mL(-)(1) with a
      detection limit (10% binding inhibition) of 2.4 ng mL(-)(1) and a dynamic range
      from 6.0 to 191 ng mL(-)(1) (20-80% binding inhibition) penicillin G. The generic
      nature of the antiserum was shown by good relative cross-reactivities with
      penicillin type beta-lactam antibiotics such as amoxicillin (50%), ampicillin
      (47%), and penicillin V (145%) and a lower response to the isoxazolyl penicillins
      such as oxacillin, cloxacillin, and dicloxacillin. No cross-reactivity was
      obtained for cephalosporin type beta-lactam antibiotics (cephapirin),
      cloramphenicol, or fluoroquinolones (enrofloxacin and ciprofloxacin). The total
      analysis time was 23 min per determination, and the immunoreactor could be reused
      for more than 200 cycles without significant loss of activity. The immunosensor
      has been successfully applied to the direct analysis of penicillin G and
      amoxicillin in spiked influent and effluent sewage treatment plant water samples
      with excellent recoveries (mean values for penicillin G and amoxicillin, 99 and
      105%, respectively). Results displayed by comparative analysis of the
      immunosensor with a chromatographic procedure for penicillins showed excellent
      agreement between both methods.

PMID- 16104779
TI  - Parallel synthesis: a new approach for developing analytical internal standards.
      Application to the analysis of patulin by gas chromatography-mass spectrometry.
AB  - The polymer-assisted reaction of 4-(hydroxymethyl)furan-2(5H)-one (4HM2F) with 21
      carboxylic acids using polystyrene-carbodiimide (PS-carbodiimide) yielded an
      ester library. Four of the esters, (5-oxo-2,5-dihydrofuran-3-yl)methyl acetate
      (IS-1), (5-oxo-2,5-dihydrofuran-3-yl)methyl butyrate (IS-2), (5-oxo-2,5
      dihydrofuran-3-yl)methyl 2-methylpropanoate (IS-3), and (5-oxo-2,5-dihydrofuran-3
      yl)methyl chloroacetate (IS-4), were tested as internal standards for the
      quantification of patulin in apple juice by gas chromatography-mass spectrometry
      in the selected ion monitoring mode (GC-MS-SIM). The developed method combines an
      AOAC official extractive step and a GC-MS-SIM analysis. Using a chromatographic
      column containing trifluoropropylmethylpolysiloxane as the stationary phase and
      IS-1 as the internal standard, it was possible to perform an accurate and precise
      quantification of underivatizated patulin in apple juice at concentrations down
      to 6 microg/L. A detection limit of 1 microg/L was established.

PMID- 16104780
TI  - Carotenoid, tocopherol, phenolic acid, and antioxidant properties of Maryland
      grown soft wheat.
AB  - Consumers' desires to either reduce the risk of or manage a specific health
      condition through improved diet have stimulated the research of agricultural
      products for their potential health beneficial components such as tocopherols and
      natural antioxidants. Soft wheat is one of the major crops in Maryland, with
      little information available about its potentially beneficial components. This
      study examined eight selected Maryland-grown soft wheat varieties or experimental
      lines for their potential beneficial components including tocopherols,
      carotenoids, total phenolics and phenolic acids and their antioxidant properties,
      including Fe(2+) chelating capacity and free radical scavenging activities
      against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(*) ), radical cation
      ABTS(*)(+), and oxygen radical (ORAC). The results showed that all tested soft
      wheat grain samples contained alpha-tocopherol, with a range of 3.4-10.1
      microg/g. Lutein was the primary carotenoid present in the grain samples at a
      level of 0.82-1.14 microg/g, along with significant amounts of zeaxanthin and
      beta-carotene. Vanillic, syringic, p-coumaric, and ferulic acids were found in
      soluble free, soluble conjugated, and insoluble bound forms in the grain
      extracts, with ferulic acid as the predominant phenolic acid. The eight soft
      wheat varieties differed in their antioxidant properties. The tested wheat grain
      samples exhibited ED(50) values against DPPH(*) of 23-27 mg of grain equiv/mL,
      ORAC of 32.9-48 micromol of Trolox equiv (TE)/g, and ABTS(*)(+) scavenging
      capacity of 14.3-17.6 micromol of TE/g. These data suggest the possibility of
      producing soft wheat varieties rich in selected health beneficial factors for
      optimum human nutrition though breeding programs.

PMID- 16104781
TI  - Differential effects of ferulic acid and p-coumaric acid on S phase distribution
      and length of S phase in the human colonic cell line Caco-2.
AB  - Ferulic acid (FA) and para-coumaric acid (p-CA) may mediate the protective
      effects of whole-grain cereals against colon cancer. Therefore, the effects of FA
      and p-CA on the metabolic activity, proliferation, cell cycle phase distribution,
      and kinetics of the colonic endothelial tumor cell line Caco-2 was studied. Both
      compounds at 1500 microM decreased the number of cells to 43-75% of control after
      2-3 days of treatment. Cell cycle phase distribution and cell cycle kinetics were
      determined by flow cytometric analysis after bromodeoxyuridine labeling. Each
      compound at 1500 microM decreased the proportion of cells in the G(1) phase and
      increased the proportion of cells in the S and G(2) phases. Treatment with 1500
      microM FA significantly increased the length of the S phase, while p-CA did not.
      It was concluded that FA and p-CA inhibited cell proliferation by presumably
      affecting different cell cycle phases, and this warrants further investigations
      because this inhibition may be one explanation for the diet-related protection
      against cancer.

PMID- 16104782
TI  - Reactive oxygen scavenging effect of enzymatic extracts from Sargassum
      thunbergii.
AB  - The free radical scavenging activity of water soluble natural antioxidants from
      Sargassum thunbergii, which is a brown marine alga, was evaluated by examining
      the radical scavenging activities of the extracts of hydrolyzates from S.
      thunbergii on hydroxyl, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and alkyl radicals.
      A spin-trapping electron spin resonance (ESR) spectrometer was employed, and the
      results were compared for their ESR signal intensity. S. thunbergii was
      enzymatically hydrolyzed to prepare water soluble extracts by five carbohydrases
      (AMG, Celluclast, Termamyl, Ultraflo, and Viscozyme) and proteases (Alcalase,
      Flavorzyme, Kojizyme, Neutrase, and Protamex). The scavenging activity of the
      radicals increased with increased concentrations of the extracts. The scavenging
      results were higher for hydroxyl and alkyl radicals and lower for DPPH radical as
      compared with vitamin C as a reference. The hydrogen peroxide scavenging activity
      of the extracts was also investigated; the Alcalase extract showed the highest
      scavenging activity among the extracts prepared with the five proteases and five
      carbohydrates. In addition, the DNA damage was determined by using the comet
      assay with alkaline electrophoresis and was quantified by measuring the tail
      length. The preventive effect of Alcalase extract from S. thunbergii against DNA
      damage increased with increments of concentration of the enzymatic extracts.

PMID- 16104783
TI  - Screening study of lead compounds for natural product-based fungicides:
      antifungal activity and biotransformation of 6alpha,7alpha-dihydroxy-beta
      himachalene by Botrytis cinerea.
AB  - Eleven beta-himachalene derivatives were tested, using the poisoning food
      technique, for their potential antifungal activity against the phytopathogen
      Botrytis cinerea. Compounds 1-11 displayed moderate activity, whereas the 6,7
      diol derivative (12) produced an inhibition of 91% after 6 days. The microbial
      transformation of 12 was investigated and yielded four new compounds hydroxylated
      at positions C-5 (13), C-2 (14), C-4 (15), and C-12 (16). The structures were
      established on the basis of their spectroscopic data including two-dimensional
      NMR analysis (HMQC, HMBC, nOesy) and nOes. The results obtained from
      biotransformation experiments shed further light on the detoxification mechanism
      of the phytopathogenic fungus against this compound and give an indication of the
      structural modifications that may be necessary if substrates of this type are to
      be further developed as selective fungal control agents for B. cinerea.

PMID- 16104784
TI  - Isolation and composition of chromoplasts from tomatoes.
AB  - The fruit of the tomato plant is composed of elongated tomato cells filled with
      organelles called chromoplasts (plastids). These plastids scattered throughout
      the cell are rich in nutrients, particularly protein (33%) and lipids (20%). They
      can be released from the cells by rupture of their cell membranes and then
      isolated. Plastids and their cell contents can be utilized by the food-processing
      industry for the preparation of special food products. This study was designed to
      examine the macronutrient content of isolated tomato plastids and, therefore,
      determine its potential nutritional value. Use of tomato plastids in pasta sauces
      and rice dishes, salsa, and extrusion products would increase the nutritional
      value of the product. Because glucose has been removed in the process of plastid
      isolation, tomato plastids are useful in the diets of diabetics and
      cardiovascular patients, as well as for patients in need of weight reduction.
      Composition comparison of tomato plastid is made with tomato paste, from which
      glucose has not been removed. Many people require low-sugar products for medical
      reasons (diabetics and those with cardiovascular disease) and others for weight
      loss. Therefore, tomato chromoplasts having high protein and lipid contents and
      low sugar content may be useful in meeting these particular human needs.

PMID- 16104785
TI  - Increasing expression of an anti-picloram single-chain variable fragment (ScFv)
      antibody and resistance to picloram in transgenic tobacco (Nicotiana tabacum).
AB  - Systematic research involving four chimeric gene constructions designed to
      express the same anti-picloram single-chain variable fragment (scFv) antibody is
      described. Agrobacterium-mediated transformation produced at least 25 transgenic
      tobacco plants with each of these, and the number of T-DNA loci in each plant was
      determined using kanamycin-resistance segregation assays. The relative amounts of
      active and total scFv in each plant were evaluated using quantitative enzyme
      linked immunosorbent assay and immunoblot technologies, respectively. No
      significant differences in scFv activity were found among the four groups of
      single-locus plants, although the 35S/M construct was found to produce
      significantly more total anti-picloram scFv than the other three constructs. A
      dose-response bioassay involving T(1) seedlings from several of the highest
      expressers of active scFv demonstrated resistance to a constant exposure of
      picloram at 5 x 10(-)(8) M. Other approaches for increasing antibody-based
      herbicide resistance are discussed, as further improvements are needed before
      practical application of this technology.

PMID- 16104786
TI  - Identification of genetically modified potato (Solanum tuberosum) cultivars using
      event specific polymerase chain reaction.
AB  - Several genetically modified (GM) cultivars are registered in Canada although
      they are not currently in commercial production. The GM cultivars can be
      distinguished from the non-GM and other GM cultivars by analyzing the DNA
      nucleotide sequence at the insertion site of the transgene corresponding to a
      single transformation event in the plant genome. Techniques based on modified
      polymerase chain reaction (PCR) strategies were used to generate sequence
      information from the plant genome flanking the insertion site of transgenic DNA
      for specific GM potato events. The plant genome sequence adjacent to the
      transgenic insertion was used to design PCR primers, which could be used in
      combination with a primer annealing to one of the nearby inserted genetic
      elements to amplify an event specific DNA fragment. The event specific PCR
      fragments generated were sequenced to confirm the specificity of the method.

PMID- 16104787
TI  - Use of bentonite and activated carbon in controlled release formulations of
      carbofuran.
AB  - Controlled release systems (CRS), unlike the conventional formulations,
      facilitate a gradual and controlled discharge of the pesticides, reducing the
      losses by evaporation and leaching and minimizing pesticide pollution. In this
      study, carbofuran-an insecticide-nematicide identified as a groundwater pollutant
      was incorporated in alginate-based granules to obtain controlled release
      properties. The effect on carbofuran release rate caused by the incorporation of
      bentonite, activated carbon, and different mixtures of both sorbents in alginate
      basic formulation was studied by immersion of the granules in water. The water
      uptake, sorption capacity of the sorbent, permeability, and time taken for 50% of
      the active ingredient to be released into water, T(50), were calculated by the
      comparison of the preparations. T(50) values were higher for those formulations
      containing bentonite and/or activated carbon (T(50) values range from 14.76 h for
      the alginate formulation containing only bentonite as the sorbent to 29.5 weeks
      for the alginate formulation containing only activated carbon as the sorbent)
      than for the preparation without these sorbents (11.72 h). On the basis of a
      parameter of an empirical equation used to fit the insecticide-nematicide release
      data, it appears that the release of carbofuran from the various formulations
      into water is controlled by a diffusion mechanism. The sorption capacity of the
      sorbents for carbofuran was the most important factor modulating carbofuran
      release. In addition, it was observed that there is a linear correlation of the
      T(50) values and the content of activated carbon in dry granules.

PMID- 16104788
TI  - Generation of decarboxylated and dehydrogenated betacyanins in thermally treated
      purified fruit extract from purple pitaya (Hylocereus polyrhizus) monitored by LC
      MS/MS.
AB  - Pigments of purple pitaya [Hylocereus polyrhizus (F.A.C. Weber) Britton and Rose]
      fruits were submitted to extraction and were decarboxylated during heating
      experiments in acidified ethanolic and aqueous solutions. Groups of betacyanins
      with different decarboxylation levels were identified in the heating products by
      LC-DAD and LC-MS/MS. The main decarboxylation products were 2-decarboxy
      betacyanins, 17-decarboxy-betacyanins, and 2,17-bidecarboxy-betacyanins. The
      structures of other compounds were assigned to 2,15,17-tridecarboxy-betacyanins
      and 14,15-dehydrogenated derivatives (neo-derivatives) of all decarboxylated
      betacyanins found.

PMID- 16104789
TI  - Identification of rat urinary and fecal metabolites of a new herbicide,
      pyribenzoxim.
AB  - Rats were treated with pyribenzoxim (O-[2,6-bis[(4,6-dimethoxy-2
      pyrimidinyl)oxy]benzoyl]oxime), a new herbicide, to investigate the related
      metabolites in urine and feces. Metabolites were identified using LC/MS
      (electrospray ionization) and GC/MS (electron impact ionization) following the
      relatively simple and rapid extraction and purification procedures. Three
      metabolites were identified in urine either from oral gavage or intravenous (iv)
      injection. They were benzophenone oxime (BO), benzophenone oxime glucuronide
      (BOG), and 2-hydroxy-6-(4,6-dimethoxypyrimidin-2-yloxy)benzoic acid (HDB).
      Benzophenone oxime was present in larger quantity than BOG and HDB in urine from
      oral treatment, while the case was opposite in urine from iv treatment.
      Glucuronide conjugate was confirmed unambiguously by enzyme hydrolysis. 2,6
      Bis(4,6-dimethoxypyrimidin-2-yloxy)benzoic acid (KIH-2023) and benzophenone were
      identified in feces. Benzophenone was confirmed by GC/MS and HPLC/DAD since LC/MS
      could not produce an ESI spectrum. On the basis of the results obtained, a
      metabolic map of pyribenzoxim is proposed.

PMID- 16104790
TI  - Residue level, persistence, and storage performance of citrus fruit treated with
      fludioxonil.
AB  - The potential of postharvest dip treatments with fludioxonil (FLU) (a synthetic
      analogue of the bacterial metabolite of pyrrolnitrin), in controlling postharvest
      decay caused by Penicillium digitatum and Penicillium italicum of citrus fruit
      was investigated in comparison with the conventional fungicide imazalil (IMZ).
      The ultrastructural changes of fruit epicuticular wax was investigated as a
      function of water dip temperature, and the possible role of these changes was
      related to residue accumulation under FLU treatment. Residues retained by fruit
      were determined as a function of fungicide concentration, dip temperature, and
      fruit storage conditions. Scanning electron microscopy analysis revealed that
      fruit dipping in water at 30 or 40 degrees C did not cause differences in
      cuticular wax's ultrastructure in comparison to control fruit, while treatments
      at 50, 55, or 60 degrees C caused the disappearance of wax platelets, resulting
      in relatively homogeneous skin surface, due to partial "melting" of epicuticular
      wax. Residues of FLU in fruit treated at 20 or 50 degrees C were significantly
      correlated with the doses of fungicide applied. When equal amounts of fungicide
      were employed, the residue concentrations were notably higher (from 2.6- to 4
      fold) in fruit treated at 50 degrees C than in fruit treated at 20 degrees C. The
      dissipation rate of FLU in "Salustiana" and "Tarocco" oranges was lower in fruit
      subjected to treatment at 50 degrees C. The minimal FLU concentration for almost
      complete decay control in artificially wounded fruit during 7-d storage at 20
      degrees C was 400 mg/L active ingredient (ai) in fruit treated at 20 degrees C
      and 100 mg/L ai in fruit treated at 50 degrees C. Results on nonwounded Tarocco
      oranges subjected to 3 weeks of simulated quarantine conditions at 1 degrees C,
      plus 6 weeks of standard storage at 8 degrees C and an additional two weeks of
      simulated marketing period (SMP) at 20 degrees C revealed that almost complete
      decay control with FLU applications of 100 mg/L at 50 degrees C and 400 mg/L at
      20 degrees C resulted in ca. 0.8 mg/kg FLU fruit residues, in agreement with
      results on wounded citrus fruit. When equal concentrations and temperatures were
      applied, FLU treatments were as effective as IMZ. In vitro trials showed a low
      sensitivity to FLU against P. digitatum and P. italicum isolates. MIC values for
      the complete inhibition of mycelium growth were >or=100 microg/mL, while ED(50)
      values ranged from 0.1 to 1 microg/mL for P. digitatum and from 1 to >100
      microg/mL for P. italicum. The latter result suggests that care should be taken
      to avoid exclusive application of FLU in a sustainable program for management of
      fruit decay. However, integrating fungicide application and hot water dip may
      reduce the possibility of selecting fungicide-resistant populations of the
      pathogen, by increasing the effectiveness of the treatment.

PMID- 16104791
TI  - Insecticidal activity of Arum maculatum tuber lectin and its binding to the
      glycosylated insect gut receptors.
AB  - Mannose binding approximately 50 kDa homotetrameric lectin, purified from edible
      Arum maculatum tuber, was analyzed through SDS-PAGE and studied for its
      agglutination property using rabbit erythrocytes. Cross reactivity of the
      purified lectin was verified through western blot using Colocasia
      esculantum(Family, Araceae) tuber lectin antibody. The insecticidal activity of
      Arum maculatum tuber lectin (ATL) was tested against two economically important
      sucking pests, Lipaphis erysimi and Aphis craccivora, in an artificial diet. The
      LC(50) values for L. erysimi and A. craccivora were determined to be 21 microg/mL
      and 16 microg/mL, respectively. Addition of alpha-d-mannose in ATL-supplemented
      diet reduced the aphid mortality. Two major receptor proteins of ATL
      (approximately 40 kDa and approximately 35 kDa) were detected from the brush
      border membrane vesicle (BBMV) protein of L. erysimi and A. craccivora guts,
      respectively, using ligand-binding assay. Alpha-d-Mannose was found to be a
      deterrent to such binding of ATL to the BBMV receptors.

PMID- 16104792
TI  - Olive pomace amendment in Mediterranean conditions: effect on soil and humic acid
      properties and wheat (Triticum turgidum L.) yield.
AB  - The effects of the addition of either crude or exhausted olive pomace at two
      rates (10 and 20 t ha(-)(1)) on soil and soil humic acid (HA) properties and
      durum wheat (Triticum turgidum L.) yield were investigated in open-field
      Mediterranean conditions. Soil amendment with olive pomaces produced a
      significant increase of total organic, total extractable, humified and
      nonhumified C forms, and available K contents. With respect to control soil HA,
      humic-like acids isolated from crude and exhausted olive pomaces were
      characterized by larger phenolic OH group contents, smaller carboxyl group
      contents, a prevalent aliphatic character, extended molecular heterogeneity, and
      smaller aromatic polycondensation and humification degrees. In general,
      application of olive pomaces to soil produced a number of modifications in soil
      HAs, including the increase of O and acidic functional group contents, C/N ratio,
      and aliphaticity and the decrease of C/H ratio and N and C contents. Wheat grain
      yield increased significantly as an effect of olive pomace amendment. In
      particular, the increases were related to kernel weight, kernel number per square
      meter, and soil organic matter content. Possibly, the enhanced amount of soil
      organic matter in olive-pomace-amended soils relieved wheat of drought stress
      from anthesis to maturity by promoting a good soil structure, thereby reducing
      water loss by evaporation.

PMID- 16104793
TI  - Transport of commercial endosulfan through a column of aggregated vineyard soil
      by a water flux simulating field conditions.
AB  - Endosulfan is a potentially harmful, degradation resistant pesticide that is
      found in soils where it has been used. Despite being hydrophobic and having high
      affinity for soil matrix components, it has also been found in groundwater. To
      investigate this behavior, we studied the passage of a commercial emulsified
      formulation through a column of aggregated vineyard soil under simulated light
      rain. Breakthrough data were obtained using gas chromatography with electron
      capture detection to determine the concentration of endosulfan in samples
      extracted from the column periodically at several depths. These data, and
      analogous data obtained previously for the passage of bromide, were analyzed
      using the program CXTFIT v.2. Analysis of the bromide data strongly suggested the
      existence of preferential flow paths in the column. The endosulfan data were
      adequately accounted for by a model in which the preferential flow and
      nonpreferential flow regions are almost isolated from each other. These regions
      differ also as regards both the partition of endosulfan between soil and soil
      solution and the rate at which reversibly adsorbed endosulfan is transformed into
      irreversibly adsorbed endosulfan. The "irreversibility" sink term accounts also
      for biological and chemical degradation of endosulfan. The findings imply that
      soil humidity favors the transport of commercial endosulfan by the formation and
      maintenance of preferential flow paths in soil, controlling both the presence of
      endosulfan in groundwater and its high persistence in soil.

PMID- 16104794
TI  - Environmental effects of inclusion complexation between methylated beta
      cyclodextrin and diclofop-methyl.
AB  - Diclofop-methyl (DM) is a broad-spectrum herbicide but often shows a reduced
      biological activity against the target grasses due to its poor water solubility
      and slow translocation within plant tissues. Randomly methylated beta
      cyclodextrin (MCD) is an effective inclusion complexation agent and, as a
      potential formulation additive, may thus improve the behavior of DM. We evaluated
      the complexing role of MCD by measuring the solubility and soil sorption of DM as
      a function of MCD concentration, as well as the dissolution rates of DM-MCD
      complexes. The complex was also extensively characterized by UV, fluorescence,
      Fourier transform infrared, nuclear magnetic resonance, and differential scanning
      calorimetry techniques. The apparent solubility of DM linearly increased with MCD
      concentration, indicating the formation of a 1:1 complex. In contrast, diclofop
      was not complexed by MCD. The DM-MCD complex appeared to have formed within the
      hydrophobic cavity of MCD. With the measured stability constant of 4740 L mol(
      )(1), the complex was apparently stable, which resulted in DM resistant to
      hydrolysis, and hence the ratio of DM to the sum of DM and diclofop increased
      toward unity with increasing MCD concentration. The DM-MCD complex also quickly
      dissolved to a maximum within 5 min, due presumably to the hydrophilicity of MCD.
      The sorption of DM by soil was significantly reduced in the presence of MCD. All
      the results suggest that MCD may effectively improve the availability of DM to
      pests and for bioremediation.

PMID- 16104795
TI  - Development of structure-taste relationships for monosubstituted phenylsulfamate
      sweeteners using classification and regression tree (CART) analysis.
AB  - Twenty monosubstituted phenylsulfamates (cyclamates) have been synthesized and
      have had their taste portfolios determined. These have been combined with 63
      compounds already in the literature to give a database of 83 ortho, meta, and
      para compounds. A training set of 75 compounds was randomly selected leaving
      eight compounds as a test set. A series of nine predictors determined with Corey
      Pauling-Koltun models, calculated from the PC SPARTAN PRO program and Hammett
      sigma values taken mainly from the literature, have been used to establish
      structure-taste relationships for these types of sweeteners. The taste panel data
      for all compounds were categorized into three classes, namely, sweet (S),
      nonsweet (N), and sweet/nonsweet (N/S), and a novel "sweetness value" or
      weighting was also calculated for each compound. Linear and quadratic
      discriminant analysis were first used with the S, N, and N/S data, but the
      results were somewhat disappointing. Classification and regression tree analysis
      using the sweetness values for all 75 compounds was more successful, and only 14
      were misclassified and six of the eight test set compounds were correctly
      classified. For the 29 meta compounds, one subset using just two parameters
      classified 83% of these compounds. Finally, using various methods, predictions
      were made on the likely tastes of a number of meta compounds and a striking
      agreement was found between the tree prediction and those given by earlier
      models. This appears to offer a strong vindication of the tree approach.

PMID- 16104796
TI  - Volatile composition and sensory characters of commercial Galician orujo spirits.
AB  - Nineteen samples of commercial Galician orujo spirits were analyzed by gas
      chromatography and distinguished from one another on the basis of the
      concentrations of major volatile compounds (methanol, higher alcohols, esters,
      acetates, and aldehydes). The spirits were also sensorily analyzed to emphasize
      this differentiation and to establish a sensory profile as a function of the
      attributes defined by the tasters. The results show that the Galician orujo
      spirits present notably significant differences in the concentrations of 2
      butanol, methanol, acetaldehyde, and ethyl lactate, whereas their ethylic esters
      contents are similar. Sensorily, the orujo spirits can be differentiated by taste
      but have similar characteristics of bouquet, the best of which are from the
      Godello variety. The descriptions employed to define the orujo spirits were
      herbaceous, floral, fruity, vegetal, alcohol, toasted, and "others". Floral and
      fruity were predominant in the Albarino orujo spirits; herbaceous was predominant
      in the plurivarietal orujo spirits, vegetal in the Godello spirits, and dried
      fruit or toasted in the Mencia spirits. The orujo spirits from Treixadura have
      the most diverse profile, with the participation of most of the attributes.

PMID- 16104797
TI  - Identification of characteristic aroma-active compounds from water dropwort
      (Oenanthe javanica DC.).
AB  - Characteristic aroma components of water dropwort (Oenanthe javanica DC.) were
      evaluated by aroma extract dilution analysis and solid-phase microextraction-gas
      chromatography-olfactometry. Alpha-Terpinolene (plastic/cucumber-like) was the
      most intense aroma-active compound in water dropwort. Other potent aroma-active
      compounds included p-cymene (kerosene-like), alpha-terpinene (lemon), (E)
      caryophyllene (woody), (Z,E)-alpha-farnesene (woody), hexanal (green), (Z)-3
      hexenol (green), phenylacetaldehyde (honey), (E)-2-nonenal (cucumber), bornyl
      acetate (cooked vegetable), and gamma-terpinene (lemon). Of these, p-cymene was
      believed to be primarily responsible for the distinct kerosene-like aroma note of
      water dropwort. The aroma property of p-cymene was dependent on its concentration
      and was described as kerosene-like at relatively high concentrations but changed
      to citrus and green aroma notes at low concentrations.

PMID- 16104798
TI  - Translational diffusion coefficients of volatile compounds in various aqueous
      solutions at low and subzero temperatures.
AB  - Translational diffusion coefficients (D(12)) of volatile compounds were measured
      in model media with the profile concentration method. The influence of sample
      temperature (from 25 to -10 degrees C) was studied on translational diffusion in
      sucrose or maltodextrin solutions at various concentrations. Results show that
      diffusivity of volatile compounds in sucrose solutions is controlled by
      temperature, molecule size, and the viscosity of the liquid phase as expected
      with the Stokes-Einstein equation; moreover, physicochemical interactions between
      volatile compounds and the medium are determinant for diffusion estimation. At
      negative temperature, the winding path induced by an ice crystal content of >70%
      lowered volatile compound diffusion. On the contrary, no influence on
      translational diffusion coefficients was observed for lower ice content.

PMID- 16104799
TI  - Generation of (E)-1-(2,3,6-trimethylphenyl)buta-1,3-diene from C13-norisoprenoid
      precursors.
AB  - Three C(13)-norisoprenoid compounds, 3,6,9-trihydroxymegastigma-4,7-diene (6),
      3,4,9-trihydroxymegastigma-5,7-diene (4), and the actinidols (8), have all been
      synthesized and subjected to acid hydrolysis. All three were shown to generate
      (E)-1-(2,3,6-trimethylphenyl)buta-1,3-diene (1) under wine conservation
      conditions. At 45 degrees C, approximately 4000-5000 ng/L of 1 was formed from
      1.0 mg/L of precursor, after 173 days, while at 25 degrees C more wine-like
      amounts (200-600 ng/L) were observed. A glucoside, 4,5-dihydrovomifoliol-C(9)
      beta-d-glucopyranoside (9b), was isolated from grapevine leaves by multilayer
      coil countercurrent chromatography (MLCCC), and its stereochemistry was deduced
      as being (5R, 6S, 9R) by NMR and CD spectroscopy. Hydrolysis of this glucoside
      produced 1, but in quantities insufficient to account for the levels observed in
      wine.

PMID- 16104800
TI  - NMR relaxation and water self-diffusion studies in whey protein solutions and
      gels.
AB  - The changes in water proton transverse relaxation behavior induced by aggregation
      of whey proteins are explained in terms of the simple molecular processes of
      diffusion and chemical exchange. The water self-diffusion coefficient was
      measured in whey protein solutions and gels by the pulsed field gradient NMR
      method. As expected, water self-diffusion was reduced with increased protein
      concentrations. Whatever the concentration, the water molecules were free to
      diffuse over distances varying from 15 to 47 mum. Water diffusion was constant
      over these distances, demonstrating that no restrictions were found to explain
      the water hindrance. The modification in protein structure by gelation induced a
      decrease in water diffusion. The effects of protein concentration on water
      diffusion are discussed and modeled. Two approaches were compared, the
      obstruction effect induced by a spherical particle and the cell model, which
      considered two water compartments with specific self-diffusion coefficients.

PMID- 16104801
TI  - Treatment of metastatic melanoma B16F10 by the flavonoids tangeretin, rutin, and
      diosmin.
AB  - Melanoma is one of the most frequently metastasizing malignant neoplasias. This
      study examines an experimental model of pulmonary metastasis and the B16F10 cell
      subline, highly metastatic in the lung. Antimetastatic effects of the flavonoids
      tangeretin, rutin, and diosmin were analyzed, and at the same time an analysis of
      the metastatic activity of ethanol was performed, considered to be necessary
      because it is used as a vehicle for administering the flavonoids. Lentini's
      model, which complements the macroscopic evaluation of nodule numbers by using a
      stereoscopic microscope and image analysis at the microscopic level, was used.
      The greatest reduction in the number of metastatic nodules (52%) was obtained
      with diosmin; similarly, the percentages of implantation, growth index, and
      invasion index (79.40, 67.44, and 45.23%, respectively), were all compared with
      those of the ethanol group, considered to be an effective control group. Rutin-
      and tangeretin-treated groups also showed reductions of the same index compared
      with the ethanol group. It would seem that structural factors would better
      explain these results and the antimetastatic activity of each flavonoid and the
      respective metabolites.

PMID- 16104802
TI  - Role of glucose in the maillard browning of maltose and glycine: a radiochemical
      approach.
AB  - We followed the contribution of released glucose to the formation of melanoidins
      in the maltose-glycine reaction by adding (14)C glucose to the maltose-glycine
      mixture, after it already had undergone some reaction. This approach allowed us
      to confirm the turnover of glucose in this reaction and hence the role of glucose
      in forming melanoidins. A comparison of the total amount of glucose converted
      into the melanoidins with the total concentration of melanoidins formed from
      maltose and glycine showed that the concentration of melanoidins originating from
      the released glucose was relatively small in comparison to the total melanoidins
      concentration. Hence, the parallel glucose-glycine reaction is considered to be
      only a minor pathway in the formation of maltose-glycine melanoidins. The
      incorporation of glucose into the nondialyzable melanoidins in the maltose
      glycine reaction was in excellent agreement with the amount estimated from a
      kinetic model for the reaction of maltose with glycine. The rate constants were
      estimated by nonlinear regression, via multiresponse modeling.

PMID- 16104803
TI  - Arachidonic acid and long-chain n-3 polyunsaturated fatty acid contents in meat
      of selected poultry and fish species in relation to dietary fat sources.
AB  - Arachidonic acid (AA) content, long-chain n-3 polyunsaturated fatty acid (PUFA)
      equivalent [LCE; calculated as 0.15 x linolenic acid (LA) + eicosapentaenoic acid
      (EPA) + docosahexaenoic acid (DHA)], and PUFA n-6/PUFA n-3 ratio were determined
      in meat [breast meat (BM), thigh meat (TM), and fillets (F), respectively] within
      four sets of chickens, five sets of turkeys, one set of common carp, and four
      sets of rainbow trout, fed either commercial diet or diets with manipulated PUFA
      n-3 and PUFA n-6 contents. AA content was within the range of 20 mg/100 g (F of
      rainbow trout fed the diet with linseed oil, LO) to 138 mg/100 g (TM of chickens
      fed restrictively the diet based on maize to the age of 90 days). AA content in
      BM of turkeys fed the diet with LO or fish oil (FO) did not differ (P > 0.05)
      from that of rainbow trout F. LCE was in the range of 16 mg/100 g (BM of turkeys
      fed a commercial feed mixture) to 681 mg/100 g (F of rainbow trout fed a
      commercial feed mixture). With regard to BM, only turkeys fed the diet with LO
      deposited more (P < 0.01) LCE (71 mg/100 g) as compared to all other poultry sets
      except turkeys fed the diet with FO (123 mg/100 g). Apart from all fish samples,
      also both BM and TM of turkeys fed the diet with either LO or FO met the
      recommended value of the PUFA n-6/PUFA n-3 ratio (<4). AA content in the tissue
      increased significantly (P < 0.001) with increasing dietary LA in both all
      chicken tissues and all turkey tissues, which is contrary to the suggested strong
      metabolic regulation of the AA formation. When all tissues within all animal
      species were taken as a one set, both AA percentage and EPA + DHA percentage in
      the tissue (Y, %) decreased (P < 0.001) with increasing fat content in the tissue
      (X, %), according to the equation Y = 4.7 - 0.54X (R (2) = 0.41) and Y = 6.0 -
      0.33X (R (2) = 0.35), respectively. AA content in chicken BM, chicken TM, and
      turkey BM, respectively, decreased linearly (P < 0.01) with increasing live
      weight reached at the slaughter age.

PMID- 16104804
TI  - Phenolic compounds and antioxidant activity of sorghum grains of varying
      genotypes.
AB  - The effects of plant color, pericarp thickness, pigmented testa, and spreader
      genes on phenols and antioxidant activity levels of 13 sorghum genotypes were
      evaluated. Total phenols, condensed tannins, flavan-4-ols, and anthocyanins were
      measured. Antioxidant activity levels using the 2,2'-azinobis(3-ethyl
      benzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl assays were
      evaluated. Sorghums with a pigmented testa and spreader genes (B(1)()B(2)()S) had
      the highest levels of phenols and antioxidant activity. In addition, sorghums
      with purple/red plants (PQ) and thick pericarp (z) genes had increased levels of
      phenols and antioxidant activity. Sorghums with a black pericarp had higher
      levels of flavan-4-ols and anthocyanins than the other varieties. This suggests
      that genes for plant color, pericarp thickness, presence of a pigmented testa,
      and spreader genes increase phenols and antioxidant activity levels. This
      information can be useful in the production of sorghums with increased phenols
      and antioxidant activity levels.

PMID- 16104805
TI  - Antioxidant capacity of some herbs/spices from cameroon: a comparative study of
      two methods.
AB  - This study evaluates the antioxidant capacity of 14 herbs/spices from Cameroon.
      Freeze-dried samples extracted in methanol (free or unconjugated polyphenol) and
      in 1.2 M hydrochloric acid (HCl) in methanol (total antioxidant that is both
      unconjugated and conjugated) were analyzed using two different antioxidant assay
      methods [Folin-Ciocalteu reagent (Folin) and the ferric reducing antioxidant
      power (FRAP)]. The 1.2 M HCl in methanol extracts had significantly higher (P <
      0.001) antioxidant capacities than the methanolic extract. Generally, the FRAP
      antioxidant values were significantly (P < 0.001) higher than the Folin
      antioxidant values. Although a significant correlation (P < 0.05) was obtained
      between the Folin phenol and the FRAP antioxidant, the trends of the antioxidant
      capacity of the samples were different for the Folin and FRAP methods. The leaves
      of the Piper species top the total antioxidant tables in both Folin and FRAP
      assay methods, respectively. Irvingia gabonensis tops the FRAP free antioxidant
      list, while Piper umbellatum leads the Folin free antioxidant followed by Thymus
      vulgaris. Thus, the antioxidant capacity of plant samples determined by different
      methods should be interpreted with caution. However, irrespective of the assay
      method used, the samples were rich in antioxidants.

PMID- 16104806
TI  - Differential activation of a latent polyphenol oxidase mediated by sodium dodecyl
      sulfate.
AB  - A kinetic study of the activity of soluble and membrane-bound latent polyphenol
      oxidase (PPO) extracted from beet root (Beta vulgaris) was carried out. For the
      first time, two types of behavior (hyperbolic and sigmoid) are reported in the
      same enzyme for PPO activation by the surfactant sodium dodecyl sulfate (SDS),
      depending on substrate nature. A kinetic model based on cooperative systems is
      developed to describe the activation effect of SDS, enabling the determination of
      the number of surfactant molecules binding to the enzyme in the activation
      process. The results indicate that the active site of the enzyme is not affected
      by SDS and that a stepwise conformational change favors the access of hydrophobic
      substrates compared to hydrophilic ones. Differential activation of PPO mediated
      by SDS may be of relevance in the control of PPO activity since the enzyme is
      able to express activity toward a specific substrate while remaining latent to
      others.

PMID- 16104807
TI  - Recovery of antioxidant activity from carnosol quinone: antioxidants obtained
      from a water-promoted conversion of carnosol quinone.
AB  - Carnosol is one of the main antioxidants in sage and rosemary. Although carnosol
      quinone is the antioxidation product of carnosol and has a very weak antioxidant
      activity, its treatment in water-containing solvent restored its strong
      antioxidant activity. HPLC analysis of the water-stimulated recovery reaction of
      the antioxidant activity revealed that the strong activity was due to the
      reproduced carnosol. The analysis also showed that an almost equal amount of
      quinone derivatives of rosmanol (rosmanol quinone) was produced in the reaction
      along with the carnosol. The rosmanol was formed by the addition of 1 equiv of
      water and the following isomerization from carnosol quinone in the water
      containing solvent. The formed rosmanol was also found to be oxidized by the
      remaining carnosol quinone to produce rosmanol quinone. At the same time,
      carnosol quinone was reduced to afford carnosol. This redox phenomenon is an
      important part of the mechanism for the recovery of the antioxidant activity from
      carnosol quinone under the water-containing conditions.

PMID- 16104808
TI  - Volatile compounds produced in cheese by pseudomonas strains of dairy origin
      belonging to six different species.
AB  - Production of volatile compounds by seven Pseudomonas strains belonging to six
      different species, Ps. brenneri, Ps. graminis, Ps. libanensis, Ps. lundensis, Ps.
      putida, and Ps. rhodesiae, was investigated, with the aim of elucidating their
      possible contribution to the volatile profile of cheese. Laboratory-scale cheeses
      were made from pasteurized milk of low bacterial counts separately inoculated
      with approximately 10(5) colony-forming units/mL of each Pseudomonas strain and
      ripened for 12 days at 10 degrees C. A total of 122 volatile compounds were
      identified in cheeses by GC-MS of the dynamic headspace. The abundance of 62
      compounds, belonging to eight chemical groups (aldehydes, ketones, acids, esters,
      alcohols, hydrocarbons, benzene compounds, and sulfur compounds) increased during
      ripening for at least one of the strains. Most groups of volatile compounds were
      more abundant in the outer part of cheeses than in the inner part, in agreement
      with the aerobic metabolism of the genus Pseudomonas and coinciding with the
      higher counts in the outer part. Production of volatile compounds in cheese by
      Pseudomonas was shown to be species-dependent.

PMID- 16104809
TI  - Hydroxylysyl pyridinoline cross-link concentration affects the textural
      properties of fresh and smoked Atlantic salmon (Salmo salar L.) flesh.
AB  - A simple HPLC method is presented to quantify the low concentration of
      hydroxylysyl pyridinoline (PYD) cross-links in Atlantic salmon (Salmo salar L.)
      muscle. The method involved the extraction of tissue with NaOH prior to
      hydrolysis, which greatly reduced the amount of protein to be hydrolyzed and made
      downstream operations easier and more reproducible. The concentration of PYD was
      426 pmol g(-)(1) dry mass muscle in post-rigor muscle stored at 0 degrees C and
      sampled 3 d after death. Hydroxproline (HYP) concentration was determined
      following NaOH extraction as a measure of collagen content. In post-rigor
      samples, the alkaline-insoluble HYP fraction comprised 18.3% of the total HYP.
      Scanning electron microscopy revealed shrinkage of muscle fibers and a retraction
      of the connective tissue matrix in smoked salmon. PYD concentration was
      relatively resistant to processing to the smoked product, decreasing by around
      11.7%, as compared to a 22.2% decrease in HYP. There was a positive correlation
      between PYD concentration and the firmness of post-rigor muscle samples as
      measured by an instrumental texture analyzer, explaining 25% of the total
      variation. A weaker but still significant correlation was found between PYD
      concentration and firmness in the smoked product. There was no relationship
      between fillet firmness and total collagen concentration, although the
      correlation with HYP in the alkaline-insoluble fraction was significant at the 6%
      level (P = 0.057). Our results indicate that only 1-3% of collagen molecules are
      linked by nonreducible mature cross-links in harvest size farmed Atlantic salmon
      and that PYD concentration is an important raw material characteristic for flesh
      quality.

PMID- 16104810
TI  - Reduced T cell response to beta-lactoglobulin by conjugation with acidic
      oligosaccharides.
AB  - We have previously reported that the conjugation of beta-lactoglobulin (beta-LG)
      with alginic acid oligosaccharide (ALGO) and phosphoryl oligosaccharides reduced
      the immunogenicity of beta-LG. In addition, those conjugates showed higher
      thermal stability and improved emulsifying properties than those of native beta
      LG. We examine in this study the effect of conjugation on the T cell response.
      Our results demonstrate that the T cell response was reduced when mice were
      immunized with the conjugates. The findings obtained from an experiment using
      overlapping synthetic peptides show that novel epitopes were not generated by
      conjugation. One of the mechanisms for the reduced T cell response to the
      conjugates was found to be the reduced susceptibility of the conjugates to
      processing enzymes for antigen presentation. We further clarify that the beta-LG
      ALGO conjugate modulated the immune response to Th1 dominance. We consider that
      this property of the beta-LG-ALGO conjugate would be effective for preventing
      food allergy as well as by its reduced immunogenicity. Our observations indicate
      that the method used in this study could be applied to various protein allergens
      to achieve reduced allergenicity with multiple improvements in their properties.

PMID- 16104811
TI  - Isoflavone conjugates are underestimated in tissues using enzymatic hydrolysis.
AB  - Many health effects of soy foods are attributed to isoflavones. Isoflavones upon
      absorption present as free form, glucuronide, and sulfate conjugates in blood,
      urine, and bile. Little is known about the molecular forms and the relative
      concentrations of soy isoflavones in target organs. Acid hydrolysis or enzymatic
      hydrolysis (glucuronidases and sulfatases) was used to study isoflavone contents
      in the heart, brain, epididymis, fat, lung, testis, liver, pituitary gland,
      prostate gland, mammary glands, uterus, and kidney from rats fed diets made with
      soy protein isolate. The heart had the lowest isoflavone contents (undetectable),
      and the kidney had the highest (1.8 +/- 0.6 nmol/g total genistein; 3.0 +/- 1.1
      nmol/g total daidzein). Acid hydrolysis released 20-60% more aglycon in tissues
      than enzymatic digestion (p < 0.05), and both hydrolysis methods gave the same
      level of isoflavones in serum. Approximately 28-44% of the total isoflavone
      content within the liver was unconjugated aglycon, and the remainder was
      conjugated mainly as glucuronide. The subcellular distribution of total
      isoflavones was 55-60% cytosolic and 13-16% in each of the nuclear,
      mitochondrial, and microsomal fractions. These results demonstrated that (1) soy
      isoflavones distribute in a wide variety of tissues as aglycon and conjugates and
      (2) the concentrations of isoflavone aglycons, which are thought to be the
      bioactive molecules, are in the 0.2-0.25 nmol/g range, far below the
      concentrations required for most in vitro effects of genistein or daidzein.

PMID- 16104812
TI  - Solvolysis procedures for the determination of bound residues of the mycotoxin
      deoxynivalenol in fusarium species infected grain of two winter wheat cultivars
      preinfected with barley yellow dwarf virus.
AB  - A trichloroacetic acid treatment at 140 degrees C for 40 min was successfully
      established as a suitable solvolysis procedure for the recovery of bound
      deoxynivalenol or its derivatives in Fusarium-infected plants. Deoxynivalenol
      itself was not decomposed in the procedure. The derivative 15-acetyl
      deoxynivalenol was chosen as a model compound for setting free deoxynivalenol in
      an acid-catalyzed deesterification reaction, developing the method. This is the
      first report using a trichloroacetic acid solvolysis procedure as a sample
      incubation step to free bound deoxynivalenol and determine free from bound
      deoxynivalenol in the sample. Between 13 and 63% of the total deoxynivalenol
      consisted of nonextractable deoxynivalenol. Deoxynivalenol contents in grain of
      the susceptible cultivar "Agent" infected with Fusarium spp. were 12-24 times
      higher when compared to those for the corresponding moderately resistant cultivar
      "Petrus". The highest deoxynivalenol amounts were determined in grain infected
      with Fusarium spp. as well as simultaneously infected with BYDV. This solvolysis
      procedure may be of importance for distinguishing between resistant and
      susceptible plants and their ability to immobilize (bound) mycotoxins as a plant
      defense mechanism.

PMID- 16104813
TI  - Antioxidant pool in beer and kinetics of EPR spin-trapping.
AB  - The kinetics of spin-trap adduct formation in beer oxidation exhibits an
      induction period if the reaction is carried out at elevated temperatures and in
      the presence of air. This lag period lasts until the endogenous antioxidants are
      almost completely depleted, and its duration is used as an indicator of the
      flavor stability and shelf life of beer. This paper demonstrates that the total
      kinetics of the process can be characterized by three parameters-the lag period,
      the rate of spin-trap adduct formation, and, finally, the steady-state spin
      adduct concentration. A steady-state chain reaction mechanism is described, and
      quantitative estimates of the main kinetic parameters such as the initiation
      rate, antioxidant pool, effective content of organic molecules participating in
      the chain reactions, and the rate constant of the 1-hydroxyethyl radical EtOH(*)
      spin-adduct disappearance are given. An additional new dimensionless parameter is
      suggested to characterize the antioxidant pool-the product of the lag time and
      the rate of spin-trap radical formation immediately after the lag time,
      normalized by the steady-state concentration of the adducts. The results of spin
      tapping EPR experiments are compared with the nitroxide reduction kinetics
      measured in the same beer samples. It is shown that although the kinetics of
      nitroxide reduction in beer can be used to evaluate the reducing power of beer,
      the latter parameter does not correlate with the antioxidant pool. The
      relationship of free radical processes, antioxidant pool, reducing power, and
      beer staling is discussed.

PMID- 16104814
TI  - A simple and efficient system for green note compound biogenesis by use of
      certain lipoxygenase and hydroperoxide lyase sources.
AB  - Six-carbon (C(6)) aldehydes and alcohols are important components of the aroma
      and flavor of fruits and vegetables. Soybean lipoxygenase (LOX) isozyme LOX 3 was
      reported not only to produce less 13-hydroperoxides, precursors of C(6)
      aldehydes, but also to convert them to ketodiene products. Here, we examined the
      effects of LOX 3 on hexenal formation from linolenic acid homogenized with
      watermelon 13-hydroperoxide lyase (HL)-overexpressing Nicotiana tabacum leaves
      and soybean acetone powder. Compared to the wild type, which contains LOXs 1, 2,
      and 3, the elimination of LOX 3 in LOX 1 + 2 facilitates greater production of
      hexenals. The use of LOX 2 alone yielded the highest hexenal production, while a
      two-step conversion was required for LOX 1 to produce hexenals at high levels due
      to different pH optima of the enzymes involved. These results clearly demonstrate
      that the soybeans lacking LOX 3 in combination with watermelon HL-overexpressing
      leaf tissues greatly enhance hexenal formation.

PMID- 16104815
TI  - Thermal stability of alpha-amylase from malted jowar (Sorghum bicolor).
AB  - Malted cereals are rich sources of alpha-amylase, which catalyzes the random
      hydrolysis of internal alpha-(1-4)-glycosidic bonds of starch, leading to
      liquefaction. Amylases play a role in the predigestion of starch, leading to a
      reduction in the water absorption capacity of the cereal. Among the three cereal
      amylases (barley, ragi, and jowar), jowar amylase is found to be the most
      thermostable. The major amylase from malted jowar, a 47 kDa alpha-amylase,
      purified to homogeneity, is rich in beta structure ( approximately 60%) like
      other cereal amylases. T(m), the midpoint of thermal inactivation, is found to be
      69.6 +/- 0.3 degrees C. Thermal inactivation is found to follow first-order
      kinetics at pH 4.8, the pH optimum of the enzyme. Activation energy, E(a), is
      found to be 45.3 +/- 0.2 kcal mol(-)(1). The activation enthalpy (DeltaH),
      entropy (DeltaS*), and free energy change (DeltaG) are calculated to be 44.6 +/-
      0.2 kcal mol(-)(1), 57.1 +/- 0.3 cal mol(-)(1) K(-)(1), and 25.2 +/- 0.2 kcal
      mol(-)(1), respectively. The thermal stability of the enzyme in the presence of
      the commonly used food additives NaCl and sucrose has been studied. T(m) is found
      to decrease to 66.3 +/- 0.3, 58.1 +/- 0.2, and 48.1 +/- 0.5 degrees C,
      corresponding to the presence of 0.1, 0.5, and 1 M NaCl, respectively. Sucrose
      acts as a stabilizer; the T(m) value is found to be 77.3 +/- 0.3 degrees C
      compared to 69.6 +/- 0.3 degrees C in the control.

PMID- 16104816
TI  - Bioactive compounds in cod (Gadus morhua) products and suitability of 1H NMR
      metabolite profiling for classification of the products using multivariate data
      analyses.
AB  - This work investigates the suitability of (1)H NMR spectroscopy to identify the
      fate of some bioactive compounds in seafood submitted to several processing
      conditions and examines the possibility of using (1)H NMR spectroscopy profiling
      to classify such products. Perchloric acid extracts of cod white muscle from
      newly killed and (i) unprocessed, (ii) boiled, and (iii) fried fillets and from
      (iv) frozen fillets, (v) the frozen fillets after thawing, and (vi) their drip
      loss and from (vii) rehydrated cod klippfish (n = 5) were analyzed by 500 MHz
      (1)H NMR spectroscopy. It was possible to identify taurine, betaine, anserine,
      creatine, and trimethylamine oxide (TMAO) in all extracts examined, and frozen
      fish was recognizable by the presence of dimethylamine (DMA). None of the heating
      procedures seemed to induce the loss of bioactive compounds from the fillet, but
      freezing and thawing did: the compounds were lost in what is known as drip loss.
      About 80% of the samples were correctly classified using a probabilistic neural
      network procedure having as inputs the scores of the first 20 principal
      components of the principal component analysis of a selected region of the NMR
      spectra.

PMID- 16104817
TI  - Antioxidant properties of prepared blueberry (Vaccinium myrtillus) extracts.
AB  - A blueberry extract (A) and two anthocyanin-derived extracts (B and C) were
      prepared. The contents of polyphenols, flavonoids, anthocyanins, and anthocyanin
      derived pigments of the extracts were determined for the first time. The pigment
      profile of blueberry extract A corresponded to 15 anthocyanins, whereas extract B
      was mainly composed of anthocyanin-pyruvic acid adducts of the blueberry original
      anthocyanins and extract C was mainly composed of the respective
      vinylpyranoanthocyanin-catechins (portisins). The extracts' abilities to inhibit
      lipid peroxidation, induced by 2,2'-azobis(2-methyl-propanimidamide)
      dihydrochloride in a liposomal membrane system were examined. The antioxidant
      capacities of the extracts were evaluated through monitoring oxygen consumption
      and by measuring the formation of conjugated dienes. All of the extracts provided
      protection of membranes against peroxyl radicals by increasing the induction time
      of oxidation. This effect increased with the polyphenol content and with the
      structural complexity of the anthocyanin-derived pigments of the extracts. The
      pigments present in extract C seemed to induce a higher protection of the
      liposome membranes toward oxidation. In addition, the antiradical properties and
      the reducing power of the extracts were determined by using DPPH and FRAP
      methods, respectively. The results from these assays were in agreement with those
      obtained with the liposome membranes.

PMID- 16104818
TI  - Quantitative variations in the essential oil of Minthostachys mollis (Kunth.)
      Griseb. in response to insects with different feeding habits.
AB  - Plants display a diverse array of inducible changes in secondary metabolites
      following insect herbivory. Herbivores differ in their feeding behavior,
      physiology, and mode of attachment to the leaf surface, and such variations might
      be reflected in the induced responses of damaged plants. Induced changes were
      analyzed for Minthostachys mollis, a Lamiaceae with medicinal and aromatic uses,
      and four species of folivore insects with different feeding habits (chewing,
      scraping, sap-sucking, and puncturing). In M. mollis leaves experimentally
      exposed to the insects, levels of the two dominant monoterpenes pulegone and
      menthone were assessed 24 and 48 h after wounding. Menthone content generally
      decreased in the essential oil of damaged leaves, whereas pulegone concentration
      increased in all treatments. These changes occurred also in the adjacent
      undamaged leaves, suggesting a systemic response. The relatively uniform response
      to different kinds of damage could be attributable to the presence of such a
      strongly active compound as pulegone in the essential oil of M. mollis. The
      effects of wounding on essential oil concentration may be significant from a
      commercial point of view.

PMID- 16104819
TI  - Effects of varied EGCG and (+)-catechin concentrations on proinflammatory
      cytokines mrna expression in cona-stimulated primary white blood cell cultures.
AB  - EGCG [(-)-epigallocatechin gallate] and (+)-catechin hydrate are flavanoids,
      which are known as anticancer and healthy drugs. To test the immune modulatory
      effects of EGCG and catechin, various concentrations were tested on primary white
      blood cells (WBC) in cell cultures stimulated with the T-cell mitogen
      concanavalin A (ConA). WBC from dairy cows (1 x 10(6) cells/mL) were cultivated
      using RPMI medium with FCS and gentamycin. First, WBC were stimulated with ConA,
      and 6 h later the flavanoid treatment was started. Cultivated WBC were treated
      with various physiological flavanol concentrations (0-100 microM) in cross
      combination with various ConA concentrations (0-1 microg/mL). After 24 h, cells
      were harvested, cell viability was verified, and total RNA was isolated. Relative
      mRNA expression levels of proinflammatory cytokines TNFalpha, IL1beta, IL6, and
      transcription factor cFos and of nucleosome component histon H3 were quantified
      with real-time qRT-PCR. High EGCG and catechin concentrations had inhibitory
      effects on total RNA expression. Low EGCG concentration can induce total RNA
      expression in WBC. EGCG reduced cFos mRNA expression, which can be abolished by
      high ConA concentrations in a reverse dose-dependent manner. TNFalpha showed a
      flavanoid-specific expression pattern. EGCG acts in blood physiological
      concentrations (micromolar range), and catechin acts in higher gut-relevant
      concentrations (millimolar range) and has the potential to influence the
      proinflammatory TNFalpha expression. Higher flavanoid concentration had more
      pronounced effects than lower, whereas EGCG showed a more potent suppression of
      gene expression than catechin (toward TNFalpha). EGCG and catechin had no
      significant effects in primary WBC on the expression pattern of the
      proinflammatory cytokines IL1beta and IL6 and on the expression of the
      housekeeping genes GAPDH and histon H3. It is presumed that both flavanoids have
      the potential to regulate total RNA expression and gene-specific expression in
      WBC.

PMID- 16104820
TI  - Antioxidant activity of Myristica malabarica extracts and their constituents.
AB  - The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay of the ether, methanol, and
      aqueous extracts of the spice Myristica malabarica (rampatri) revealed the
      methanol extract to possess the best antioxidant activity. Column chromatography
      of the methanol extract led to the isolation of a new 2-acylresorcinol and four
      known diarylnonanoids of which the diarylnonanoid, malabaricone C, showed the
      maximum DPPH scavenging activity. Malabaricone C could prevent both Fe(II)- and
      2,2'-azobis(2-amidinopropane)dihydrochloride-induced lipid peroxidation (LPO) of
      rat liver mitochondria more efficiently than curcumin. The anti-LPO activity of
      malabaricone C was attributed to its better radical scavenging and Fe(II)
      chelation capacities. The superior activity of malabaricone C was rationalized by
      a systematic structure-activity correlation of the results obtained with the
      structurally related diarylnonanoids and curcumin. Malabaricone C also prevented
      the gamma-ray-induced damage of pBR322 plasmid DNA in a concentration-dependent
      manner. The radioprotective activity was found to correlate with its (*)OH
      radical scavenging property, which matched well with that of d-mannitol.

PMID- 16104821
TI  - Lactic acid decreases Fe(II) and Fe(III) retention but increases Fe(III)
      transepithelial transfer by Caco-2 cells.
AB  - Lactic acid (LA) has been proposed to be an enhancer for dietary iron absorption,
      but contradictory results have also been reported. In the present study, fully
      differentiated Caco-2 cell monolayers were used to evaluate the effects of LA (1
      50 mmol/L) on the cellular retention and transepithelial transport of soluble non
      heme iron (as ferric nitrilotriacetate). Our data revealed a linear decline in
      Fe(III) retention with respect to the concentration of LA added. In the presence
      of 50 mmol/L LA, retention of Fe(III) and Fe(II) decreased 57% and 58%,
      respectively. In contrast, transfer of Fe(III) across the cell monolayer was
      doubled, while Fe(II) transfer across the cell monolayer decreased 35%. We
      conclude that LA reduces cellular retention and transepithelial transport of
      Fe(II) by Caco-2 cells in a dose-dependent manner. However, while LA also reduces
      retention of Fe(III) by Caco-2 cells, the transfer of Fe(III) across cell
      monolayers is enhanced, possibly due to effects on paracellular transport.

PMID- 16104822
TI  - Effect of ethanol and red wine on ochratoxin a-induced experimental acute
      nephrotoxicity.
AB  - Ochratoxin A (OTA), is a nephrotoxic mycotoxin present in wine, which is
      nephrotoxic in humans. Our working hypothesis is that natural substances in wine
      may counteract OTA toxicity. Thirty-six rats were randomized to OTA dissolved in
      saline, red wine, or 13.5% ethanol or to OTA-free wine, ethanol, or saline. OTA
      (289 microg/kg of body weight/48 h) was administered by gastric gavage for 2
      weeks. Serum creatinine, tubular enzymuria, renal lipohydroperoxides (LOOH),
      reduced (GSH) and oxidized (GSSG) glutathione, and renal superoxide dismutase
      activity (SOD) were determined in renal tissue. OTA alone produced significant
      increases in renal lipoperoxides and significant decreases in SOD and GSH/GSSG
      ratio. In red wine or ethanol, OTA was less nephrotoxic, reducing oxidative
      damage as revealed by LOOH. In OTA-wine and OTA-ethanol groups, SOD activity was
      higher than in the OTA-treated one, suggesting that both ethanol and nonalcoholic
      fractions may preserve antioxidant reserve. GSH/GSSG ratio was significantly
      preserved only in the OTA-wine group and not in OTA-ethanol. Red wine may exert a
      protective effect against OTA nephrotoxicity by limiting oxidative damage. The
      ostensible protection afforded by ethanol deserves further investigation.

PMID- 16104823
TI  - Influence of mycotoxin producing fungi (Fusarium, Aspergillus, Penicillium) on
      gluten proteins during suboptimal storage of wheat after harvest and competitive
      interactions between field and storage fungi.
AB  - Cereals contaminated by Aspergillus spp., Penicillium spp., and Fusarium spp. and
      their mycotoxins, for example, ochratoxin A (OTA) and deoxynivalenol (DON), are
      not only a risk to human and animal health but can also show poor technological
      properties and baking quality. The influence of these genera on the sulfur
      speciation of low molecular weight (LMW) subunits of glutenin was characterized
      by investigating suboptimally stored wheat samples in situ by X-ray absorption
      near edge structure (XANES) spectroscopy and baking tests. Field fungi of the
      genus Fusarium have hardly any influence on both the sulfur speciation of wheat
      gluten proteins and the baking properties, whereas storage fungi of the genera
      Aspergillus and Penicillium have a direct influence. An increased amount of
      sulfur in sulfonic acid state was found, which is not available for
      thiol/disulfide exchange reactions in the gluten network, and thus leads to a
      considerably reduced baking volume. From changes of the composition of the mould
      flora during suboptimal storage of wheat and from the mycotoxin contents, it can
      be concluded that microbial competitive interactions play an important role in
      the development of the mould flora and the mycotoxin concentrations during
      (suboptimal) storage of wheat.

PMID- 16104824
TI  - Solid- and vapor-phase antimicrobial activities of six essential oils:
      susceptibility of selected foodborne bacterial and fungal strains.
AB  - The antimicrobial activity of essential oils (EOs) of cinnamon (Cinnamon
      zeylanicum), clove (Syzygium aromaticum), basil (Ocimum basillicum), rosemary
      (Rosmarinus officinalis), dill (Anethum graveolens), and ginger (Zingiber
      officinalis) was evaluated over a range of concentrations in two types of contact
      tests (solid and vapor diffusion). The EOs were tested against an array of four
      Gram-positive bacteria (Staphylococcus aureus, Bacillus cereus, Enterococcus
      faecalis, and Listeria monocytogenes), four Gram-negative bacteria (Escherichia
      coli, Yersinia enterocolitica, Salmonella choleraesuis, and Pseudomonas
      aeruginosa), and three fungi (a yeast, Candida albicans, and two molds,
      Penicillium islandicum and Aspergillus flavus). The rationale for this work was
      to test the possibility of creating a protective atmosphere by using natural
      compounds that could extend the shelf life of packaged foodstuffs while
      minimizing organoleptic alterations. In the solid diffusion tests, cinnamon and
      clove gave the strongest (and very similar) inhibition, followed by basil and
      rosemary, with dill and ginger giving the weakest inhibition. The fungi were the
      most sensitive microorganisms, followed by the Gram-positive bacterial strains.
      The Gram-negative strain P. aeruginosa was the least inhibited. The composition
      of the atmosphere generated by the EOs, and their minimum inhibitory
      concentrations (MICs), were determined using a disk volatilization method, in
      which no inhibition from rosemary or basil was observed. Cinnamon and clove, once
      again, gave similar results for every microorganism. As a general rule, MIC
      (fungi) << MIC (bacteria) with no clear differences between Gram-positive or 
      negative strains except for P. aeruginosa, which was not inhibited by any of the
      EOs in the vapor phase. The atmosphere generated from the EOs was analyzed by
      means of solid-phase microextraction combined with gas chromatography-ion trap
      mass spectrometry. Differences among the volatiles in the EOs, which may be
      responsible for the differences in their antimicrobial performances, were found.

PMID- 16104825
TI  - Development of a sensitive enzyme-linked immunosorbent assay for the
      determination of ochratoxin A.
AB  - Polyclonal antibodies for ochratoxin A (OTA) were generated from rabbits after
      the animals had been immunized with either OTA-gamma-globulin or OTA- keyhole
      limpet hemocyanin (KLH). A competitive direct enzyme-linked immunosorbent assay
      (cdELISA) and a competitive indirect ELISA (ciELISA) were used for the
      characterization of the antibodies and for analysis of OTA in various
      agricultural commodities. The antibody titers in the serum of rabbits immunized
      with OTA-gamma-globulin were considerably higher than those in rabbits immunized
      with OTA-KLH. The antibodies from the rabbits immunized with OTA-gamma-globulin
      were further characterized. In the cdELISA, the concentrations causing 50%
      inhibition (IC(50)) of binding of OTA-horseradish peroxidase to the antibodies by
      OTA, ochratoxin B (OTB), and ochratoxin C (OTC) were found to be 0.90, 110, and
      0.54 ng/mL, respectively. When 10 to 250 ng/g of standard OTA was spiked to
      soybean samples and then extracted with 50% aqueous methanol, the recovery rate
      of OTA was found to be 85.9% in the cdELISA. Analysis of OTA in various
      agricultural commodities showed that 12 of the 20 examined samples were
      contaminated with OTA at levels from 16 to 160 ng/g. The efficacy of cdELISA was
      also confirmed by the high-performance liquid chromatography method.

PMID- 16104827
TI  - Croup is associated with the novel coronavirus NL63.
AB  - BACKGROUND: The clinical relevance of infections with the novel human coronavirus
      NL63 (HCoV-NL63) has not been investigated systematically. We therefore
      determined its association with disease in young children with lower respiratory
      tract infection (LRTI). METHODS AND FINDINGS: Nine hundred forty-nine samples of
      nasopharyngeal secretions from children under 3 y of age with LRTIs were analysed
      by a quantitative HCoV-NL63-specific real-time PCR. The samples had been
      collected from hospitalised patients and outpatients from December 1999 to
      October 2001 in four different regions in Germany as part of the prospective
      population-based PRI.DE study and analysed for RNA from respiratory viruses.
      Forty-nine samples (5.2%), mainly derived from the winter season, were positive
      for HCoV-NL63 RNA. The viral RNA was more prevalent in samples from outpatients
      (7.9%) than from hospitalised patients (3.2%, p = 0.003), and co-infection with
      either respiratory syncytial virus or parainfluenza virus 3 was observed
      frequently. Samples in which only HCoV-NL63 RNA could be detected had a
      significantly higher viral load than samples containing additional respiratory
      viruses (median 2.1 x 10(6) versus 2.7 x 10(2) copies/ml, p = 0.0006). A strong
      association with croup was apparent: 43% of the HCoV-NL63-positive patients with
      high HCoV-NL63 load and absence of co-infection suffered from croup, compared to
      6% in the HCoV-NL63-negative group, p < 0.0001. A significantly higher fraction
      (17.4%) of samples from croup patients than from non-croup patients (4.2%)
      contained HCoV-NL63 RNA. CONCLUSION: HCoV-NL63 infections occur frequently in
      young children with LRTI and show a strong association with croup, suggesting a
      causal relationship.

PMID- 16104828
TI  - Inhibition of endothelial activation: a new way to treat cerebral malaria?
AB  - BACKGROUND: Malaria is still a major public health problem, partly because the
      pathogenesis of its major complication, cerebral malaria (CM), remains
      incompletely understood. However tumor necrosis factor (TNF) is thought to play a
      key role in the development of this neurological syndrome, as well as lymphotoxin
      alpha (LT). METHODS AND FINDINGS: Using an in vitro model of CM based on human
      brain-derived endothelial cells (HBEC-5i), we demonstrate the anti-inflammatory
      effect of LMP-420, a 2-NH2-6-Cl-9-[(5-dihydroxyboryl)-pentyl] purine that is a
      transcriptional inhibitor of TNF. When added before or concomitantly to TNF, LMP
      420 inhibits endothelial cell (EC) activation, i.e., the up-regulation of both
      ICAM-1 and VCAM-1 on HBEC-5i surfaces. Subsequently, LMP-420 abolishes the
      cytoadherence of ICAM-1-specific Plasmodium falciparum-parasitized red blood
      cells on these EC. Identical but weaker effects are observed when LMP-420 is
      added with LT. LMP-420 also causes a dramatic reduction of HBEC-5i vesiculation
      induced by TNF or LT stimulation, as assessed by microparticle release.
      CONCLUSION: These data provide evidence for a strong in vitro anti-inflammatory
      effect of LMP-420 and suggest that targeting host cell pathogenic mechanisms
      might provide a new therapeutic approach to improving the outcome of CM patients.

PMID- 16104829
TI  - Linking new information to a reactivated memory requires consolidation and not
      reconsolidation mechanisms.
AB  - A new memory is initially labile and becomes stabilized through a process of
      consolidation, which depends on gene expression. Stable memories, however, can
      again become labile if reactivated by recall and require another phase of protein
      synthesis in order to be maintained. This process is known as reconsolidation.
      The functional significance of the labile phase of reconsolidation is unknown;
      one hypothesis proposes that it is required to link new information with
      reactivated memories. Reconsolidation is distinct from the initial consolidation,
      and one distinction is that the requirement for specific proteins or general
      protein synthesis during the two processes occurs in different brain areas. Here,
      we identified an anatomically distinctive molecular requirement that doubly
      dissociates consolidation from reconsolidation of an inhibitory avoidance memory.
      We then used this requirement to investigate whether reconsolidation and
      consolidation are involved in linking new information with reactivated memories.
      In contrast to what the hypothesis predicted, we found that reconsolidation does
      not contribute to the formation of an association between new and reactivated
      information. Instead, it recruits mechanisms similar to those underlying
      consolidation of a new memory. Thus, linking new information to a reactivated
      memory is mediated by consolidation and not reconsolidation mechanisms.

PMID- 16104830
TI  - Facilitation of task performance and removal of the effects of sleep deprivation
      by an ampakine (CX717) in nonhuman primates.
AB  - The deleterious effects of prolonged sleep deprivation on behavior and cognition
      are a concern in modern society. Persons at risk for impaired performance and
      health-related issues resulting from prolonged sleep loss would benefit from
      agents capable of reducing these detrimental effects at the time they are sleep
      deprived. Agents capable of improving cognition by enhancing brain activity under
      normal circumstances may also have the potential to reduce the harmful or
      unwanted effects of sleep deprivation. The significant prevalence of excitatory
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamatergic
      receptors in the brain provides a basis for implementing a class of drugs that
      could act to alter or remove the effects of sleep deprivation. The ampakine CX717
      (Cortex Pharmaceuticals), a positive allosteric modulator of AMPA receptors, was
      tested for its ability to enhance performance of a cognitive, delayed match-to
      sample task under normal circumstances in well-trained monkeys, as well as
      alleviate the detrimental effects of 30-36 h of sleep deprivation. CX717 produced
      a dose-dependent enhancement of task performance under normal alert testing
      conditions. Concomitant measures of regional cerebral metabolic rates for glucose
      (CMRglc) during the task, utilizing positron emission tomography, revealed
      increased activity in prefrontal cortex, dorsal striatum, and medial temporal
      lobe (including hippocampus) that was significantly enhanced over normal alert
      conditions following administration of CX717. A single night of sleep deprivation
      produced severe impairments in performance in the same monkeys, accompanied by
      significant alterations in task-related CMRglc in these same brain regions.
      However, CX717 administered to sleep-deprived monkeys produced a striking removal
      of the behavioral impairment and returned performance to above-normal levels even
      though animals were sleep deprived. Consistent with this recovery, CMRglc in all
      but one brain region affected by sleep deprivation was also returned to the
      normal alert pattern by the drug. The ampakine CX717, in addition to enhancing
      cognitive performance under normal alert conditions, also proved effective in
      alleviating impairment of performance due to sleep deprivation. Therefore, the
      ability to activate specific brain regions under normal alert conditions and
      alter the deleterious effects of sleep deprivation on activity in those same
      regions indicate a potential role for ampakines in sustaining performance under
      these types of adverse conditions.

PMID- 16104831
TI  - Estimation of the total parasite biomass in acute falciparum malaria from plasma
      PfHRP2.
AB  - BACKGROUND: In falciparum malaria sequestration of erythrocytes containing mature
      forms of Plasmodium falciparum in the microvasculature of vital organs is central
      to pathology, but quantitation of this hidden sequestered parasite load in vivo
      has not previously been possible. The peripheral blood parasite count measures
      only the circulating, relatively non-pathogenic parasite numbers. P. falciparum
      releases a specific histidine-rich protein (PfHRP2) into plasma. Quantitative
      measurement of plasma PfHRP2 concentrations may reflect the total parasite
      biomass in falciparum malaria. METHODS AND FINDINGS: We measured plasma
      concentrations of PfHRP2, using a quantitative antigen-capture enzyme-linked
      immunosorbent assay, in 337 adult patients with falciparum malaria of varying
      severity hospitalised on the Thai-Burmese border. Based on in vitro production
      rates, we constructed a model to link this measure to the total parasite burden
      in the patient. The estimated geometric mean parasite burden was 7 x 10(11) (95%
      confidence interval [CI] 5.8 x 10(11) to 8.5 x 10(11)) parasites per body, and
      was over six times higher in severe malaria (geometric mean 1.7 x 10(12), 95% CI
      1.3 x 10(12) to 2.3 x 10(12)) than in patients hospitalised without signs of
      severity (geometric mean 2.8 x 10(11), 95% CI 2.3 x 10(11) to 3.5 x 10(11); p <
      0.001). Parasite burden was highest in patients who died (geometric mean 3.4 x
      10(12), 95% CI 1.9 x 10(12) to 6.3 x 10(12); p = 0.03). The calculated number of
      sequestered parasites increased with disease severity and was higher in patients
      with late developmental stages of P. falciparum present on peripheral blood
      smears. Comparing model and laboratory estimates of the time of sequestration
      suggested that admission to hospital with uncomplicated malaria often follows
      schizogony-but in severe malaria is unrelated to stage of parasite development.
      CONCLUSION: Plasma PfHRP2 concentrations may be used to estimate the total body
      parasite biomass in acute falciparum malaria. Severe malaria results from
      extensive sequestration of parasitised erythrocytes.

PMID- 16104832
TI  - The European rare diseases therapeutic initiative.

PMID- 16104833
TI  - What can we do to improve child health in southern Italy?

PMID- 16104834
TI  - Nuclear weapons 60 years on: still a global public health threat.

PMID- 16104837
TI  - Screening for Modulators of G Protein-Coupled Receptors.

PMID- 16104838
TI  - Cleavage of oximes using a solid supported hypervalent organoiodine reagent.
AB  - A facile and efficient oxidative cleavage of oximes to form carbonyl compounds is
      reported using phenyl iodonium (III) diacetate (PIDA) and polymer supported
      polydiacetoxyiodostyrene. Regeneration of carbonyl compounds from corresponding
      oximes is an important reaction, since oxime derivatives constitute one of the
      primary methods for purification and characterization of carbonyl compounds. This
      process overcomes many of the disadvantages associated with other oxidative
      methods such as long reaction times, difficulties in isolation of products and
      formation of over oxidized products.

PMID- 16104840
TI  - Aquaporin-1 in the peritoneal membrane: implications for peritoneal dialysis and
      endothelial cell function.
AB  - PD (peritoneal dialysis) is an established mode of renal replacement therapy,
      based on the exchange of fluid and solutes between blood in peritoneal
      capillaries and a dialysate that has been introduced into the peritoneal cavity.
      The dialysis process involves diffusive and convective transports and osmosis
      through the PM (peritoneal membrane). Computer simulations predicted that the PM
      contains ultrasmall pores (radius <3 A, 1 A=10(-10) m), responsible for up to 50%
      of UF (ultrafiltration), i.e. the osmotically driven water movement during PD.
      Several lines of evidence suggest that AQP1 (aquaporin-1) is the ultrasmall pore
      responsible for transcellular water permeability during PD. Treatment with
      corticosteroids induces the expression of AQP1 in the PM and improves water
      permeability and UF in rats without affecting the osmotic gradient and
      permeability for small solutes. Studies in knockout mice provided further
      evidence that osmotically driven water transport across the PM is mediated by
      AQP1. AQP1 and eNOS (endothelial nitric oxide synthase) show a distinct
      regulation within the endothelium lining the peritoneal capillaries. In acute
      peritonitis, the up-regulation of eNOS and increased release of nitric oxide
      dissipate the osmotic gradient and prevent UF, whereas AQP1 expression is
      unchanged. These results illustrate the usefulness of the PM to investigate the
      role and regulation of AQP1 in the endothelium. The results also emphasize the
      critical role of AQP1 during PD and suggest that manipulation of AQP1 expression
      may be used to increase water permeability across the PM.

PMID- 16104841
TI  - Mitochondrial DNA: an advance in eukaryotic cell biology in the 1960s.
AB  - Between 1950 and 1960 mitochondria were recognized as well-characterized
      organelles of animal and fungal cells. They shared more functional autonomy than
      other cellular structures. The transmission of some mitochondrial characteristics
      did not obey Mendelian rules and followed cytoplasmic inheritance patterns. Was
      this situation a consequence of still unknown complexities? We present a personal
      account on how approaches were set up to test very different hypotheses. In the
      end, it was shown that mitochondria had their own DNA, mitochondrial DNA, and
      that this molecule carried information specific to these organelles.

PMID- 16104842
TI  - NADPH oxidase and endothelial cell function.
AB  - Intracellular ROS (reactive oxygen species) such as superoxide and H2O2 have been
      increasingly appreciated to have a role in endothelial pathophysiology. Of the
      several sources within the vasculature, a family of multi-subunit NADPH oxidases
      appears to be a predominant contributor of endothelial superoxide. More
      importantly, this enzyme system is activated by numerous stimuli and is involved
      in triggering diverse intracellular signalling pathways ('redox-sensitive'
      signalling pathways) that have a central role in conditions such as endothelial
      activation and inflammation, cell growth, apoptosis and hypertrophy. Furthermore,
      NADPH oxidase-derived superoxide contributes to the impairment of endothelium
      dependent vasodilatation by inactivating nitric oxide; the resultant endothelial
      dysfunction is implicated in the pathophysiology of diseases such as
      atherosclerosis, hypertension, diabetic vasculopathy and heart failure. A
      detailed understanding of the regulation of NADPH oxidases and their modulation
      and downstream effects may define novel therapeutic targets for cardiovascular
      disease prevention and treatment in the clinical setting, in contrast with global
      antioxidant therapy which has to date been disappointing.

PMID- 16104843
TI  - The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role
      under physiological and pathological conditions.
AB  - The VEGF (vascular endothelial growth factor) family and its receptors are
      essential regulators of angiogenesis and vascular permeability. Currently, the
      VEGF family consists of VEGF-A, PlGF (placenta growth factor), VEGF-B, VEGF-C,
      VEGF-D, VEGF-E and snake venom VEGF. VEGF-A has at least nine subtypes due to the
      alternative splicing of a single gene. Although the VEGF165 isoform plays a
      central role in vascular development, recent studies have demonstrated that each
      VEGF isoform plays distinct roles in vascular patterning and arterial
      development. VEGF-A binds to and activates two tyrosine kinase receptors, VEGFR
      (VEGF receptor)-1 and VEGFR-2. VEGFR-2 mediates most of the endothelial growth
      and survival signals, but VEGFR-1-mediated signalling plays important roles in
      pathological conditions such as cancer, ischaemia and inflammation. In solid
      tumours, VEGF-A and its receptor are involved in carcinogenesis, invasion and
      distant metastasis as well as tumour angiogenesis. VEGF-A also has a
      neuroprotective effect on hypoxic motor neurons, and is a modifier of ALS
      (amyotrophic lateral sclerosis). Recent progress in the molecular and biological
      understanding of the VEGF/VEGFR system provides us with novel and promising
      therapeutic strategies and target proteins for overcoming a variety of diseases.

PMID- 16104844
TI  - Role of resistin in obesity, insulin resistance and Type II diabetes.
AB  - Resistin is a member of a class of cysteine-rich proteins collectively termed
      resistin-like molecules. Resistin has been implicated in the pathogenesis of
      obesity-mediated insulin resistance and T2DM (Type II diabetes mellitus), at
      least in rodent models. In addition, resistin also appears to be a pro
      inflammatory cytokine. Taken together, resistin, like many other adipocytokines,
      may possess a dual role in contributing to disease risk. However, to date there
      has been considerable controversy surrounding this 12.5 kDa polypeptide in
      understanding its physiological relevance in both human and rodent systems.
      Furthermore, this has led some to question whether resistin represents an
      important pathogenic factor in the aetiology of T2DM and cardiovascular disease.
      Although researchers still remain divided as to the role of resistin, this review
      will place available data on resistin in the context of our current knowledge of
      the pathogenesis of obesity-mediated diabetes, and discuss key controversies and
      developments.

PMID- 16104845
TI  - Genetics of Paget's disease of bone.
AB  - PDB (Paget's disease of bone) is a common condition characterized by focal
      increases in bone turnover affecting one or more sites throughout the skeleton.
      Genetic factors are important in the pathogenesis of PDB and many families have
      been described where PDB is inherited in an autosomal-dominant fashion. Several
      candidate loci for susceptibility to PDB and related syndromes have been
      identified by genome-wide scans and recent evidence suggests that mutations in
      genes that encode components of the RANK [receptor activator of NF-kappaB
      (nuclear factor-kappaB)]/NF-kappaB signalling pathway play an important role in
      the pathogenesis of this group of diseases. Insertion mutations in the TNFRSF11A
      gene encoding RANK have been identified as the cause of familial expansile
      osteolysis, some cases of early onset PDB and expansile skeletal
      hyperphosphatasia. Inactivating mutations in the TNFRSF11B gene that encodes OPG
      (osteoprotegerin) have been found to cause the syndrome of juvenile PDB.
      Polymorphisms in OPG also appear to increase the risk of developing PDB. The most
      important causal gene for classical PDB is Sequestosome 1 (SQSTM1), which is a
      scaffold protein in the NF-kappaB signalling pathway, and mutations affecting the
      UBA (ubiquitin-associated) domain of this protein occur in between 20-50% of
      familial and 10-20% of sporadic PDB cases. The rare syndrome of IBMPFD (inclusion
      body myopathy, PDB and fronto-temporal dementia) is due to mutations in the VCP
      gene and these also cluster in the domain of VCP that interacts with ubiquitin,
      suggesting a common disease mechanism with SQSTM1-mediated PDB.

PMID- 16104846
TI  - Cloning and functional identification of slc5a12 as a sodium-coupled low-affinity
      transporter for monocarboxylates (SMCT2).
AB  - We report in the present paper, on the isolation and functional characterization
      of slc5a12, the twelfth member of the SLC5 gene family, from mouse kidney. The
      slc5a12 cDNA codes for a protein of 619 amino acids. Heterologous expression of
      slc5a12 cDNA in mammalian cells induces Na+-dependent transport of lactate and
      nicotinate. Several other short-chain monocarboxylates compete with nicotinate
      for the cDNA-induced transport process. Expression of slc5a12 in Xenopus oocytes
      induces electrogenic and Na+-dependent transport of lactate, nicotinate,
      propionate and butyrate. The substrate specificity of slc5a12 is similar to that
      of slc5a8, an Na+-coupled transporter for monocarboxylates. However, the
      substrate affinities of slc5a12 were much lower than those of slc5a8. slc5a12
      mRNA is expressed in kidney, small intestine and skeletal muscle. In situ
      hybridization with sagittal sections of mouse kidney showed predominant
      expression of slc5a12 in the outer cortex. This is in contrast with slc5a8, which
      is expressed in the cortex as well as in the medulla. The physiological function
      of slc5a12 in the kidney is likely to mediate the reabsorption of lactate. In the
      intestinal tract, slc5a12 is expressed in the proximal parts, whereas slc5a8 is
      expressed in the distal parts. The expression of slc5a12 in the proximal parts of
      the intestinal tract, where there is minimal bacterial colonization, suggests
      that the physiological function of slc5a12 is not to mediate the absorption of
      short-chain monocarboxylates derived from bacterial fermentation but rather to
      mediate the absorption of diet-derived short-chain monocarboxylates. Based on the
      functional and structural similarities between slc5a8 and slc5a12, we suggest
      that the two transporters be designated as SMCT1 (sodium-coupled monocarboxylate
      transporter 1) and SMCT2 respectively.

PMID- 16104847
TI  - Polyglutamine tract-binding protein-1 dysfunction induces cell death of neurons
      through mitochondrial stress.
AB  - Polyglutamine tract-binding protein-1 (PQBP-1) is a nuclear protein that
      interacts and colocalizes with mutant polyglutamine proteins. We previously
      reported that PQBP-1 transgenic mice show a late-onset motor neuron disease-like
      phenotype and cell death of motor neurons analogous to human neurodegeneration.
      To investigate the molecular mechanisms underlying the motor neuron death, we
      performed microarray analyses using the anterior horn tissues of the spinal cord
      and compared gene expression profiles between pre-symptomatic transgenic and age
      matched control mice. Surprisingly, half of the spots changed more than 1.5-fold
      turned out to be genes transcribed from the mitochondrial genome. Northern and
      western analyses confirmed up-regulation of representative mitochondrial genes,
      cytochrome c oxidase (COX) subunit 1 and 2. Immunohistochemistry revealed that
      COX1 and COX2 proteins are increased in spinal motor neurons. Electron
      microscopic analyses revealed morphological abnormalities of mitochondria in the
      motor neurons. PQBP-1 overexpression in primary neurons by adenovirus vector
      induced abnormalities of mitochondrial membrane potential from day 5, while
      cytochrome c release and caspase 3 activation were observed on day 9. An increase
      of cell death by PQBP-1 was also confirmed on day 9. Collectively, these results
      indicate that dysfunction of PQBP-1 induces mitochondrial stress, a key molecular
      pathomechanism that is shared among human neurodegenerative disorders.

PMID- 16104848
TI  - A developmental profile of the levels of calcium pumps in chick cerebellum.
AB  - The functional expression and distribution of intracellular ATPase
      (sarco(endo)plasmic reticulum Ca(2+)-ATPase: SERCA) and plasma membrane Ca(2+)
      ATPase (PMCA) was analyzed in the developing chick cerebellum. The activity and
      Ca(2+) uptake increase with development for both ATPases. However, the protein
      content increases with the stage of development only for SERCA, remaining
      constant for PMCA. Immunohistochemical assays showed that the ontogenesis of
      these ATPases goes along with definite stages of cerebellum histogenesis, and is
      complete at hatching. The SERCA is mainly distributed in Purkinje neurons,
      whereas the PMCA seems to be expressed initially in climbing fibers, shifting to
      soma and spiny branchlets of Purkinje cells at late embryonic stages. Granule
      cells express both ATPases according to their degree of maturity, whereas only
      PMCA is present in cerebellar glomeruli. These pumps are present in deep nuclei
      and the choroid plexus, although in this latter tissue their expression declines
      with development. The spatio-temporal distribution of SERCA and PMCA must be
      closely related to their association with the development of specific cells and
      processes of the chick cerebellum.

PMID- 16104849
TI  - Amyloid beta-peptide(1-42) and hydrogen peroxide-induced toxicity are mediated by
      TRPM2 in rat primary striatal cultures.
AB  - Amyloid beta-peptide (Abeta) is the main component of senile plaques which
      characterize Alzheimer's disease and may induce neuronal death through mechanisms
      which include oxidative stress. To date, the signalling pathways linking oxidant
      stress, a component of several neurodegenerative diseases, to cell death in the
      CNS are poorly understood. Melastatin-like transient receptor potential 2 (TRPM2)
      is a Ca(2+)-permeant non-selective cation channel, which responds to increases in
      oxidative stress levels in the cell and is activated by oxidants such as hydrogen
      peroxide. We demonstrate here that Abeta and hydrogen peroxide both induce death
      in cultured rat striatal cells which express TRPM2 endogenously. Transfection
      with a splice variant that acts as a dominant negative blocker of TRPM2 function
      (TRPM2-S) inhibited both hydrogen peroxide- and Abeta-induced increases in
      intracellular-free Ca(2+) and cell death. Functional inhibition of TRPM2
      activation by the poly(ADP-ribose)polymerase inhibitor SB-750139, a modulator of
      intracellular pathways activating TRPM2, attenuated hydrogen peroxide- and Abeta
      induced cell death. Furthermore, a small interfering RNA which targets TRPM2,
      reduced TRPM2 mRNA levels and the toxicity induced by hydrogen peroxide and
      Abeta. These data demonstrate that activation of TRPM2, functionally expressed in
      primary cultures of rat striatum, contributes to Abeta- and oxidative stress
      induced striatal cell death.

PMID- 16104850
TI  - Induction of mitochondrial oxidative stress in astrocytes by nitric oxide
      precedes disruption of energy metabolism.
AB  - Inhibition of the mitochondrial electron transport chain (ETC) ultimately limits
      ATP production and depletes cellular ATP. However, the individual complexes of
      the ETC in brain mitochondria need to be inhibited by approximately 50% before
      causing significant depression of ATP synthesis. Moreover, the ETC is the key
      site for the production of intracellular reactive oxygen species (ROS) and
      inhibition of one or more of the complexes of the ETC may increase the rate of
      mitochondrial ROS generation. We asked whether partial inhibition of the ETC, to
      a degree insufficient to perturb oxidative phosphorylation, might nonetheless
      induce ROS production. Chronic increase in mitochondrial ROS might then cause
      oxidative damage to the ETC sufficient to produce prolonged changes in ETC
      function and so compound the defect. We show that the exposure of astrocytes in
      culture to low concentrations of nitric oxide (NO) induces an increased rate of
      O2*- generation that outlasts the presence of NO. No effect was seen on oxygen
      consumption, lactate or ATP content over the 4-6 h that the cells were exposed to
      NO. These data suggest that partial ETC inhibition by NO may initially cause
      oxidative stress rather than ATP depletion, and this may subsequently induce
      irreversible changes in ETC function providing the basis for a cycle of damage.

PMID- 16104851
TI  - Ferroplasma and relatives, recently discovered cell wall-lacking archaea making a
      living in extremely acid, heavy metal-rich environments.
AB  - For several decades, the bacterium Acidithiobacillus (previously Thiobacillus)
      has been considered to be the principal acidophilic sulfur- and iron-oxidizing
      microbe inhabiting acidic environments rich in ores of iron and other heavy
      metals, responsible for the metal solubilization and leaching from such ores, and
      has become the paradigm of such microbes. However, during the last few years, new
      studies of a number of acidic environments, particularly mining waste waters,
      acidic pools, etc., in diverse geographical locations have revealed the presence
      of new cell wall-lacking archaea related to the recently described, acidophilic,
      ferrous-iron oxidizing Ferroplasma acidiphilum. These mesophilic and moderately
      thermophilic microbes, representing the family Ferroplasmaceae, were numerically
      significant members of the microbial consortia of the habitats studied, are able
      to mobilize metals from sulfide ores, e.g. pyrite, arsenopyrite and copper
      containing sulfides, and are more acid-resistant than iron and sulfur oxidizing
      bacteria exhibiting similar eco-physiological properties. Ferroplasma cell
      membranes contain novel caldarchaetidylglycerol tetraether lipids, which have
      extremely low proton permeabilities, as a result of the bulky isoprenoid core,
      and which are probably a major contributor to the extreme acid tolerance of these
      cell wall-less microbes. Surprisingly, several intracellular enzymes, including
      an ATP-dependent DNA ligase have pH optima close to that of the external
      environment rather than of the cytoplasm. Ferroplasma spp. are probably the major
      players in the biogeochemical cycling of sulfur and sulfide metals in highly
      acidic environments, and may have considerable potential for biotechnological
      applications such as biomining and biocatalysis under extreme conditions.

PMID- 16104852
TI  - Loss of diversity of ammonia-oxidizing bacteria correlates with increasing
      salinity in an estuary system.
AB  - Ammonia-oxidizing bacteria (AOB) play an important role in nitrogen cycling in
      estuaries, but little is known about AOB diversity, distribution and activity in
      relation to the chemical and physical changes encountered in estuary systems.
      Although estuarine salinity gradients are well recognized to influence microbial
      community structure, few studies have examined the influence of varying salinity
      on the diversity and stability of AOB populations. To investigate these
      relationships, we collected sediment samples from low-, mid- and high-salinity
      sites in Plum Island Sound estuary, MA, during spring and late summer over 3
      years. Ammonia-oxidizing bacteria distribution and diversity were assessed by
      terminal restriction fragment length polymorphism (TRFLP) analysis of the ammonia
      monooxygenase (amoA) gene, and fragments were identified by screening amoA clone
      libraries constructed from each site. Most striking was the stability and low
      diversity of the AOB community at the high-salinity site, showing little
      variability over 3 years. Ammonia-oxidizing bacteria at the high-salinity site
      were not closely related to any cultured AOB, but were most similar to
      Nitrosospira spp. Ammonia-oxidizing bacteria at the mid- and low-salinity sites
      were distributed among Nitrosospira-like sequences and sequences related to
      Nitrosomonas ureae/oligotropha and Nitrosomonas sp. Nm143. Our study suggests
      that salinity is a strong environmental control on AOB diversity and distribution
      in this estuary.

PMID- 16104853
TI  - Communities of nirS-type denitrifiers in the water column of the oxygen minimum
      zone in the eastern South Pacific.
AB  - The major sites of water column denitrification in the ocean are oxygen minimum
      zones (OMZ), such as one in the eastern South Pacific (ESP). To understand the
      structure of denitrifying communities in the OMZ off Chile, denitrifier
      communities at two sites in the Chilean OMZ (Antofagasta and Iquique) and at
      different water depths were explored by terminal restriction fragment length
      polymorphism analysis and cloning of polymerase chain reaction (PCR)-amplified
      nirS genes. NirS is a functional marker gene for denitrification encoding
      cytochrome cd1-containing nitrite reductase, which catalyses the reduction of
      nitrite to nitric oxide, the key step in denitrification. Major differences were
      found between communities from the two geographic locations. Shifts in community
      structure occurred along a biogeochemical gradient at Antofagasta. Canonical
      correspondence analysis indicated that O2, NO3-, NO2- and depth were important
      environmental factors governing these communities along the biogeochemical
      gradient in the water column. Phylogenetic analysis grouped the majority of
      clones from the ESP in distinct clusters of genes from presumably novel and yet
      uncultivated denitrifers. These nirS clusters were distantly related to those
      found in the water column of the Arabian Sea but the phylogenetic distance was
      even higher compared with environmental sequences from marine sediments or any
      other habitat. This finding suggests similar environmental conditions trigger the
      development of denitrifiers with related nirS genotypes despite large geographic
      distances.

PMID- 16104854
TI  - Response and adaptation of different methanotrophic bacteria to low methane
      mixing ratios.
AB  - Described genera of methanotrophic bacteria are present in most upland soils, but
      it is not known whether these are sufficiently oligotrophic to oxidize methane at
      its trace atmospheric mixing ratio of 1.75 ppmv. Members of the genera
      Methylocystis, Methylosinus, Methylocaldum and Methylobacter were isolated from
      different upland soils and compared with type strains for growth and activity
      under low methane mixing ratios. The specific affinity (a0s) varied by about one
      order of magnitude among different methanotrophs. It was highest in some
      Methylocystis spp., suggesting that these were the most oligotrophic. In direct
      tests, the threshold mixing ratio of methane required by most methanotrophs for
      growth ranged from 100 to greater than 1000 ppmv. However, two Methylocystis
      strains grew at only 10-100 ppmv of methane and one oxidized atmospheric methane
      for >3 months with little or no decline in the absolute rate. The results show
      that some cultivated methanotrophic bacteria are much more oligotrophic than
      others, and may contribute to atmospheric methane oxidation in soils. However, it
      is likely that these need additional energy sources for long-term survival, and
      that uncultivated groups of methanotrophic bacteria are primarily responsible for
      the process in soils possessing high methane oxidation rates.

PMID- 16104855
TI  - Use of DNA-stable isotope probing and functional gene probes to investigate the
      diversity of methyl chloride-utilizing bacteria in soil.
AB  - Enrichment and isolation of methyl chloride-utilizing bacteria from various
      terrestrial environments, including woodland and forest soils, resulted in the
      identification of seven methyl chloride-utilizing strains belonging to the genus
      Hyphomicrobium, an Aminobacter strain TW23 and strain WG1, which grouped closely
      with the genus Mesorhizobium. Methyl chloride enrichment cultures were dominated
      by Hyphomicrobium species, indicating that these bacteria were most suited to
      growth under the enrichment and isolation conditions used. However, the
      application of culture-independent techniques such as DNA-stable isotope probing
      and the use of a functional gene probe targeting cmuA, which encodes the
      methyltransferase catalysing the first step in bacterial methyl chloride
      metabolism, indicated a greater diversity of methyl chloride-utilizing bacteria
      in the terrestrial environment, compared with the diversity of soil isolates
      obtained via the enrichment and isolation procedure. It also revealed the
      presence of as yet uncultured and potentially novel methyl chloride-degrading
      bacteria in soil.

PMID- 16104856
TI  - 16S rDNA phylogeny and distribution of lin genes in novel hexachlorocyclohexane
      degrading Sphingomonas strains.
AB  - Hexachlorocyclohexane (HCH) is a highly recalcitrant pesticide that persists in
      soils. Three novel HCH-degrading strains (DS2, DS2-2 and DS3-1) were isolated
      after enrichment from HCH-contaminated soil from Germany. These strains
      efficiently degraded the alpha-, gamma- and delta-isomers of HCH, while strain
      DS3-1 also degraded beta-HCH. Based on 16S rDNA analysis, strain DS3-1 was
      closely related to Sphingomonas taejonensis, while strains DS2 and DS2-2 were
      closely related to Sphingomonas flava and seven HCH-degrading strains recently
      isolated from HCH-contaminated Spanish soil. Hence, geographic origin of the
      strains was not reflected in their phylogenetic affiliation. Subsequently, lin
      genes involved in HCH degradation, virtually identical to those from Sphingomonas
      paucimobilis strains UT26 from Japan and B90A from India, were identified in
      strains DS3-1, DS2, DS2-2 and five of the strains from Spain. The conserved lin
      gene sequences and structural organization, as well as the close association with
      IS6100, suggest a shared lin gene origin and recent horizontal gene transfer
      among phylogenetically diverged Sphingomonas strains in remote geographic
      locations. The loss of the ability to degrade gamma-HCH was associated with the
      deletion of the linA gene, probably due to recombination involving IS6100
      elements, of which several copies are located in the lin cluster region.

PMID- 16104857
TI  - Chromosomally located gene fusions constructed in Acinetobacter sp. ADP1 for the
      detection of salicylate.
AB  - Acinetobacter sp. ADP1 is a common soil-associated bacterium with high natural
      competency, allowing it to efficiently integrate foreign DNA fragments into its
      chromosome. This property was exploited to engineer salicylate-inducible luxCDABE
      and green fluorescent protein (GFP) variants of Acinetobacter sp. ADP1.
      Specifically, Acinetobacter sp. ADPWH_lux displayed the higher sensitivity when
      comparing the two variants (minimum detection c. 0.5-1 microM salicylate) and a
      faster turnover of the lux marker gene, making it suitable for whole-cell
      luminescence assays of salicylate concentration. In contrast, the longer
      maturation and turnover times of the GFP protein make the Acinetobacter sp.
      ADPWH_gfp variant more suited to applications involving whole-cell imaging of the
      presence of salicylate. The sensitivity of the luxCDABE variant was demonstrated
      by assaying salicylate production in naphthalene-degrading cultures. Assays using
      ADPWH_lux specifically mapped the kinetics of salicylate production from
      naphthalene and were similar to that observed by high-performance liquid
      chromatography (HPLC) data. However, ADPWH_lux exhibited the higher sensitivity,
      when compared with HPLC, for detecting salicylate production during the first 24
      h of naphthalene metabolism. These data demonstrate that the engineered
      Acinetobacter variants have significant potential for salicylate detection
      strategies in laboratory and field studies, especially in scenarios where genetic
      stability of the construct is required for in situ monitoring.

PMID- 16104858
TI  - Cultivation-independent in situ molecular analysis of bacteria involved in
      degradation of pentachlorophenol in soil.
AB  - The central aim of this study was to determine which components of an indigenous
      bacterial community in pristine grassland soil were capable of degrading
      pentachlorophenol (PCP) using two cultivation-independent, in situ, molecular
      techniques. The first involved polymerase chain reaction (PCR) and reverse
      transcription polymerase chain reaction (RT-PCR) amplification of 16S rRNA genes
      from DNA and RNA, respectively, extracted from PCP-amended soil. The second
      involved stable isotope probing (SIP), with incubation of soil with 13C-PCP and
      molecular analysis of 13C-labelled RNA, derived from cells incorporating PCP or
      its breakdown products, after separation from 12C-RNA by ultracentrifugation.
      Bacterial communities were characterized by denaturing gradient gel
      electrophoresis (DGGE) analysis of amplification products. PCP was degraded at an
      approximate rate of 1.18+/-0.25 (SEM) mg kg-1 day-1 and 39% of the measurable PCP
      fraction was degraded after incubation for 63 days. PCP degradation was
      associated with significant changes in bacterial community structure, leading to
      the appearance of seven bands in both DNA- and RNA-based DGGE profiles, the
      latter providing clearer evidence of qualitative shifts in community structure.
      The majority of novel bands increased in relative intensity during the first 35
      days and subsequently decreased in relative intensity as incubation continued.
      Sequence and phylogenetic analysis of six of these bands indicated most to have
      closest database relatives that were uncultured bacteria with sequence homologies
      to reported hydrocarbon degraders. No band could be detected in RNA-SIP-DGGE
      profiles derived from 13C-RNA fractions at day 0 but several faint bands appeared
      in these fractions after incubation of soil for 4 days, indicating assimilation
      of PCP or its degradation products. These bands increased in intensity during
      subsequent incubation for 21 days and decreased with further incubation. With one
      exception, RNA-SIP-DGGE and RNA-DGGE profiles were similar, indicating that RNA
      targeted DGGE, in this case, provided a good indication of the metabolically
      active microbial community.

PMID- 16104859
TI  - Recombination within sympatric cryptic species of the insect pathogenic fungus
      Metarhizium anisopliae.
AB  - Metarhizium anisopliae is an insect pathogenic fungus with a worldwide
      distribution. It is being developed and used as a biocontrol agent against a wide
      range of insect pests but relatively little is known of the life history of this
      fungus. We tested hypotheses concerning reproductive isolation and recombination
      in a sample of heat-active (ability to grow at 37 degrees C) and cold-active
      (ability to grow at 8 degrees C) sympatrically occurring isolates of M.
      anisopliae from Ontario, Canada by assaying nucleotide sequence variation at six
      polymorphic loci: the internally transcribed spacer (ITS) region of the nuclear
      ribosomal DNA repeat, and portions of calmodulin (CAL), chitin synthase (CHS),
      subtilisin-like protease (PR1), neutral trehalase (NTL) and actin (ACT)-encoding
      genes. The most parsimonious trees constructed showed a topology consistent with
      the heat-active and cold-active isolates as two monophyletic groups. We then
      applied Genealogical Concordance Phylogenetic Species Recognition (GCPSR) to the
      genealogical trees and concluded that the transition from concordance among
      branches to incongruity among branches delimited two species of M. anisopliae
      within Ontario. The GCPSR of two species was supported by intraspecific
      incongruity within each species when tested using the Partition Homogeneity test,
      indicating recombination. The GCPSR of two species also corresponded to the heat
      active and cold-active groups. As the groups are morphologically
      indistinguishable we applied the term 'cryptic species'. Therefore, the
      sympatrically occurring heat-active and cold-active isolates represent different
      cryptic species with a history of recombination among isolates within each
      species.

PMID- 16104860
TI  - Evolutionary innovation: a bone-eating marine symbiosis.
AB  - Symbiotic associations between microbes and invertebrates have resulted in some
      of the most unusual physiological and morphological adaptations that have evolved
      in the animal world. We document a new symbiosis between marine polychaetes of
      the genus Osedax and members of the bacterial group Oceanospirillales, known for
      heterotrophic degradation of complex organic compounds. These organisms were
      discovered living on the carcass of a grey whale at 2891 m depth in Monterey
      Canyon, off the coast of California. The mouthless and gutless worms are unique
      in their morphological specializations used to obtain nutrition from decomposing
      mammalian bones. Adult worms possess elaborate posterior root-like extensions
      that invade whale bone and contain bacteriocytes that house intracellular
      symbionts. Stable isotopes and fatty acid analyses suggest that these unusual
      endosymbionts are likely responsible for the nutrition of this locally abundant
      and reproductively prolific deep-sea worm.

PMID- 16104861
TI  - Pseudomonas syringae genes induced during colonization of leaf surfaces.
AB  - The foliar pathogen and ice nucleator, Pseudomonas syringae pv. syringae B728a,
      demonstrates a high level of epiphytic fitness on plants. Using a promoter
      trapping strategy termed habitat-inducible rescue of survival (HIRS), we
      identified genes of this organism that are induced during colonization of healthy
      bean leaf surfaces. These plant-inducible genes (pigs) encode diverse cellular
      functions including virulence, transcription regulation, transport, nutrient
      acquisition and other known and unknown loci, some of which may result in
      antisense transcripts to annotated P. syringae genes. Prominent among the pigs
      was ssuE, a gene in the sulfate-starvation regulon, indicating that sulfate is
      not abundant on leaf surfaces. inaZ reporter gene fusion assays of the plant
      inducible loci revealed up to 300-fold higher levels of pig transcriptional
      activity on plant leaves compared with minimal medium. However, the maximum
      levels of pig transcriptional activity were typically too weak to be measured
      using a gfp reporter gene. One exception was orf6 in the hrp/hrc pathogenicity
      island which was highly induced in epiphytic P. syringae cells. Four pigs were
      disrupted by insertional mutagenesis. While growth of the ssuE mutant was
      impaired under certain conditions in laboratory medium, the epiphytic and
      virulence properties of the mutants on bean plants were identical to wild-type P.
      syringae. Our results demonstrate the utility of HIRS to identify genes expressed
      on leaves and provide new insight into the leaf surface environment.

PMID- 16104862
TI  - In situ substrate conversion and assimilation by nitrifying bacteria in a model
      biofilm.
AB  - Local nitrification and carbon assimilation activities were studied in situ in a
      model biofilm to investigate carbon yields and contribution of distinct
      populations to these activities. Immobilized microcolonies (related to
      Nitrosomonas europaea/eutropha, Nitrosomonas oligotropha, Nitrospira sp., and to
      other Bacteria) were incubated with [14C]-bicarbonate under different
      experimental conditions. Nitrifying activity was measured concomitantly with
      microsensors (oxygen, ammonium, nitrite, nitrate). Biofilm thin sections were
      subjected to fluorescence in situ hybridization (FISH), microautoradiography
      (MAR), and local quantification of [14C]-bicarbonate uptake (beta microimaging).
      Nitrifying activity and tracer assimilation were restricted to a surface layer of
      different thickness in the various experiments (substrate or oxygen limitation).
      Excess oxygen uptake under all conditions revealed heterotrophic activity fuelled
      by decay or excretion products during active nitrification. Depth limits and
      intensity of tracer incorporation profiles were in agreement with ammonia
      oxidation activity (measured with microsensors), and distribution of incorporated
      tracer (detected with MAR). Microautoradiography revealed a sharp individual
      response of distinct populations in terms of in-/activity depending on the
      (local) environmental conditions within the biofilm. Net in situ carbon yields on
      N, expressed as e- equivalent ratios, varied between 0.005 and 0.018, and, thus,
      were in the lower range of data reported for pure cultures of nitrifiers.

PMID- 16104863
TI  - Analysis of the distribution and diversity in recent Hawaiian volcanic deposits
      of a putative carbon monoxide dehydrogenase large subunit gene.
AB  - A putative carbon monoxide dehydrogenase large subunit gene (BMS putative coxL)
      was amplified from genomic DNA extracts of four recent (42-300 year old) Hawaiian
      volcanic deposits by polymerase chain reaction (PCR). Sequence databases derived
      from clone libraries constructed using PCR products were analysed
      phylogenetically and statistically. These analyses indicated that each of the
      deposits supported distinct BMS putative coxL gene assemblages. Statistical
      analyses also showed that the youngest deposit (42 years old) contained the least
      diverse sequences (P<0.05), but that diversity did not vary significantly among
      three older deposits with ages from about 108-300 years. Although diversity
      indices did not vary among the older deposits, mismatch analyses suggested
      population structures increased in complexity with increasing deposit age. At
      each of the sites, most of the clone sequences appeared to originate from
      Proteobacteria not currently represented in culture or recognized as CO
      oxidizers.

PMID- 16104864
TI  - The molecular diversity of freshwater picoeukaryotes from an oligotrophic lake
      reveals diverse, distinctive and globally dispersed lineages.
AB  - The recent discovery of a diverse phylogenetic assemblage of picoeukaryotes from
      environments such as oceans, salt marshes and acidic habitats, has expanded the
      debates about the extent and origin of microbial eukaryotes. However, the
      diversity of these eukaryote microorganisms, that overlap bacteria in size, and
      their environmental and biogeographical ubiquity remains poorly understood. Here
      we survey picoeukaryotes (microbial eukaryotes of 0.2-5 microm in size) from an
      oligotrophic (nutrient deficient) freshwater habitat using ribosomal RNA gene
      sequences. Three taxonomic groups the Heterokonta, Cryptomonads and the Alveolata
      dominated the detected diversity. Most sequences represented previously unsampled
      species, with several being unassignable to known taxonomic groups and plausibly
      represent new or unsampled phyla. Many freshwater phylogenetic groups identified
      in this study appeared unrelated to picoeukaryotic sequences identified in marine
      ecosystems, suggesting that aspects of eukaryote microbial diversity are specific
      to certain aquatic environments. Conversely, at least five phylogenetic clusters
      comprised sequences from freshwater and globally dispersed and often contrasting
      environments, supporting the concept that a number of picoeukaryotic lineages are
      widely distributed.

PMID- 16104865
TI  - Natural microbial diversity in superficial sediments of Milazzo Harbor (Sicily)
      and community successions during microcosm enrichment with various hydrocarbons.
AB  - Hydrocarbon-contaminated superficial sediments collected from the Harbor of
      Milazzo (Tirrenean Sea, northern Sicily), a zone strongly affected by
      anthropogenic activities, were examined for in situ biodegradative capacities. A
      culture-independent molecular phylogenetic approach was used to study the
      influence of hydrocarbon and nutrient addition on the activity and diversity of
      the indigenous microbiota during a microcosm evaluation. The autochthonous
      microbial community in non-polluted sediments was represented by eubacterial
      phylotypes grouped within Proteobacteria, CFB and Firmicutes. The archaeal domain
      was represented by members of Marine Group I of Crenarchaeota. The majority of
      recovered sequences was affiliated with heterotrophic genera Clostridium and
      Vibrio, typical members of eutrophic coastal environments. Amendments of
      hydrocarbons and mineral nutrients to microcosms dramatically changed the initial
      diversity of the microbial community. Only bacterial phylotypes affiliated with
      Proteobacteria and CFB division were detected. The decrease in diversity observed
      in several microcosms could be explained by the strong selection for
      microorganisms belonging to group of marine hydrocarbonoclastic gamma
      Proteobacteria, namely Alcanivorax, Cycloclasticus, Marinobacter,
      Marinobacterium/Neptunomonas and Thalassolituus. This study demonstrated that
      nutrient amendment to hydrocarbon-contaminated superficial sediments enhanced the
      indigenous microbial biodegradation activity and that highly specialized marine
      hydrocarbonoclastic bacteria, representing a minor fraction in the natural
      microbial community, play an important role in the biodegradation of petroleum
      hydrocarbons accidentally entering the coastal environment.

PMID- 16104866
TI  - Isolation and characterization of Dehalococcoides sp. strain FL2, a
      trichloroethene (TCE)- and 1,2-dichloroethene-respiring anaerobe.
AB  - A strictly anaerobic bacterium was isolated from tetrachloroethene (PCE)-to
      ethene dechlorinating microcosms established with river sediment without prior
      exposure to chlorinated solvents. The isolation procedure included the addition
      of 2-bromoethanesulfonate to select against methanogenic archaea, >50 consecutive
      1-2% (v/v) transfers to reduced mineral salts medium amended with trichloroethene
      (TCE), acetate, and hydrogen, the addition of ampicillin, and the dilution-to
      extinction principle. Culture-dependent and 16S rRNA gene-targeted approaches
      suggested culture purity. Microscopic examination revealed a homogeneous culture
      of an organism with a distinct, disc-shaped morphology. The isolate shared >99%
      16S rRNA gene sequence similarity with members of the Pinellas group of the
      Dehalococcoides cluster, and was designated Dehalococcoides sp. strain FL2.
      Strain FL2 could be propagated with TCE, cis-1,2-dichloroethene (cis-DCE), or
      trans-DCE as the electron acceptors, acetate as the carbon source, and hydrogen
      as the electron donor in defined, completely synthetic medium. No other growth
      supporting redox couples were identified. Trichloroethene, cis-DCE and trans-DCE
      were dechlorinated at rates of 27.5, 30.4 and 18.8 micromol l-1 day-1
      respectively. Quantitative real-time polymerase chain reaction (PCR) with a
      fluorescently labelled linear hybridization probe confirmed growth with these
      electron acceptors, and suggested that strain FL2 captures energy from both the
      TCE-to-cis-DCE and 1,2-DCE-to-VC dechlorination steps. Tetrachloroethene and
      vinyl chloride (VC) were slowly and cometabolically dechlorinated in the presence
      of a growth-supporting chloroethene, but ethene formation was incomplete, even
      after prolonged incubation. At room temperature, strain FL2 grew with a doubling
      time of 2.4 days, and yielded 166.1+/-10.2 mg of protein per mole of chloride
      released. In the presence of excess electron acceptor, strain FL2 consumed
      hydrogen to a concentration of 0.061+/-0.016 nM. Dechlorination ceased following
      the addition of 0.5 mM sulfite, whereas sulfate (10 mM) and nitrate (5 mM) had no
      inhibitory effects.

PMID- 16104867
TI  - Novel vacuolate sulfur bacteria from the Gulf of Mexico reproduce by reductive
      division in three dimensions.
AB  - Large spherical sulfur bacteria, 180-375 microm in diameter, were found regularly
      and in abundance in surface sediments collected from hydrocarbon seeps (water
      depth 525-640 m) in the Gulf of Mexico. These bacteria were characterized by a
      thin 'shell' of sulfur globule-filled cytoplasm that surrounded a central vacuole
      (roughly 80% of biovolume) containing high concentrations of nitrate (average 460
      mM). Approximately 800 base pairs of 16S rRNA gene sequence data, linked to this
      bacterium by fluorescent in situ hybridization, showed 99% identity with
      Thiomargarita namibiensis, previously described only from sediments collected off
      the coast of Namibia (Western Africa). Unlike T. namibiensis, where cells form a
      linear chain within a common sheath, the Gulf of Mexico strain occurred as single
      cells and clusters of two, four and eight cells, which were clearly the product
      of division in one to three planes. In sediment cores maintained at 4 degrees C,
      which undoubtedly experienced a diminishing flux of hydrogen sulfide over time,
      the Thiomargarita-like bacterium remained viable for up to 2 years. During that
      long period, each cell appeared to undergo (as judged by change in biovolume) one
      to three reductive divisions, perhaps as a dispersal strategy in the face of
      diminished availability of its putative electron donor.

PMID- 16104868
TI  - Gene expression analysis of the mechanism of inhibition of Desulfovibrio vulgaris
      Hildenborough by nitrate-reducing, sulfide-oxidizing bacteria.
AB  - Sulfate-reducing bacteria (SRB) are inhibited by nitrate-reducing, sulfide
      oxidizing bacteria (NR-SOB) in the presence of nitrate. This inhibition has been
      attributed either to an increase in redox potential or to production of nitrite
      by the NR-SOB. Nitrite specifically inhibits the final step in the sulfate
      reduction pathway. When the NR-SOB Thiomicrospira sp. strain CVO was added to mid
      log phase cultures of the SRB Desulfovibrio vulgaris Hildenborough in the
      presence of nitrate, sulfate reduction was inhibited. Strain CVO reduced nitrate
      and oxidized sulfide, with transient production of nitrite. Sulfate reduction by
      D. vulgaris resumed once nitrite was depleted. A DNA macroarray with open reading
      frames encoding enzymes involved in energy metabolism of D. vulgaris was used to
      study the effects of NR-SOB on gene expression. Shortly following addition of
      strain CVO, D. vulgaris genes for cytochrome c nitrite reductase and hybrid
      cluster proteins Hcp1 and Hcp2 were upregulated. Genes for sulfate reduction
      enzymes, except those for dissimilatory sulfite reductase, were downregulated.
      Genes for the membrane-bound electron transferring complexes QmoABC and DsrMKJOP
      were downregulated and unaffected, respectively, whereas direct addition of
      nitrite downregulated both operons. Overall the gene expression response of D.
      vulgaris upon exposure to strain CVO and nitrate resembled that observed upon
      direct addition of nitrite, indicating that inhibition of SRB is primarily due to
      nitrite production by NR-SOB.

PMID- 16104870
TI  - Fungal manganese oxidation in a reduced soil.
AB  - Manganese chemistry in soils is a function of complex, competing biotic and
      abiotic reactions. The role of soil-borne fungi in mediating these reactions is
      poorly understood. The objective of this article is to document direct
      observation of fungal Mn oxidation in soil under near in situ conditions, and to
      isolate, describe and confirm the role of fungi in the observed Mn oxidation, and
      present a model to explain our observations. We incubated soil under different
      moisture contents in sample cells designed to allow us to use synchrotron
      microspectroscopic techniques to analyse areas as small as 38x40 microm2. Mn was
      redistributed and accumulated in distinct small circular shapes or in dendritic
      patterns near the air-soil interface when water-saturated soil was incubated for
      >or=7 days. Mn oxidation did not occur at 3 or 52 degrees C indicating that
      oxidation was caused by microbial activity. Mn-oxidizing fungi were isolated from
      the sample cells and cultured on agar. Reinoculation of sterile soil with the Mn
      oxidizing isolates resulted in the formation of Mn oxides around fungal hyphae. A
      model to describe the distinct zonal distribution of Mn oxides in the sample
      cells is presented. We believe that our data are the first direct observation of
      Mn oxidation by soil-inhabiting fungi under in situ conditions. Mn-oxidizing
      fungi may play an underappreciated role in the cycling of Mn in soils.

PMID- 16104871
TI  - Pathogenicity of vibrios to rainbow trout (Oncorhynchus mykiss, Walbaum) and
      Artemia nauplii.
AB  - The taxonomy of marine vibrios has changed rapidly over the last two decades, and
      a wealth of new species have been identified. Many Vibrio species are pathogenic
      to fish and crustaceans; however, little is known about the virulence of many of
      the novel species. The purpose of this study was to determine the ability of
      various recent isolates of vibrios to cause disease in rainbow trout
      (Oncorhynchus mykiss, Walbaum) and crustacea, i.e. Artemia nauplii. Of 56
      isolates, representing 26 species of Enterovibrio, Photobacterium and Vibrio,
      obtained from a diversity of healthy and diseased aquatic animal hosts and water
      samples from many geographical locations, Vibrio brasiliensis, V.
      coralliilyticus, V. ezurae, V. fortis, V. kanaloaei, V. neptunius, V.
      rotiferianus and V. tubiashii were pathogenic to rainbow trout and Artemia
      nauplii with mortalities of up to 100%. The extracellular products of these
      pathogenic isolates were harmful to the animal models. In contrast, cultures of
      Enterovibrio norvegicus, E. coralii, Photobacterium rosenbergii, Vibrio
      campbellii, V. chagasii, V. cyclitrophicus, V. gallicus, V. gigasii, V.
      hepatarius, V. hispanicus, V. lentus, V. nereis, V. pacini, V. pomeroyi, V.
      shilonii, V. superstes, V. tasmaniensis and V. xuii demonstrated either non- or
      low virulence in the animal models.

PMID- 16104869
TI  - Coupling 16S-ITS rDNA clone libraries and automated ribosomal intergenic spacer
      analysis to show marine microbial diversity: development and application to a
      time series.
AB  - We outline an approach to simultaneously assess multilevel microbial diversity
      patterns utilizing 16S-ITS rDNA clone libraries coupled with automated ribosomal
      intergenic spacer analysis (ARISA). Sequence data from 512 clones allowed
      estimation of ARISA fragment lengths associated with bacteria in a coastal marine
      environment. We matched 92% of ARISA peaks (each comprising >1% total amplified
      product) with corresponding lengths from clone libraries. These peaks with
      putative identification accounted for an average of 83% of total amplified
      community DNA. At 16S rDNA similarities <98%, most taxa displayed differences in
      ARISA fragment lengths >10 bp, readily detectable and suggesting ARISA resolution
      is near the 'species' level. Prochlorococcus abundance profiles from ARISA were
      strongly correlated (r2=0.86) to Prochlorococcus cell counts, indicating ARISA
      data are roughly proportional to actual cell abundance within a defined taxon.
      Analysis of ARISA profiles for 42 months elucidated patterns of microbial
      presence and abundance providing insights into community shifts and ecological
      niches for specific organisms, including a coupling of ecological patterns for
      taxa within the Prochlorococcus, the Gamma Proteobacteria and Actinobacteria.
      Clade-specific ARISA protocols were developed for the SAR11 and marine
      cyanobacteria to resolve ambiguous identifications and to perform focused
      studies. 16S-ITS data allowed high-resolution identification of organisms by ITS
      sequence analysis, and examination of microdiversity.

PMID- 16104873
TI  - Delineation and molecular characterization of acute myeloid leukemia patients
      with coduplication of FLT3 and MLL.
AB  - Partial tandem (PTD) and internal tandem duplications (ITD) of the MLL or FLT3
      genes respectively, have been demonstrated in acute myeloid leukemia (AML). While
      occurrence of each of these PTD/ITD seem to confer an unfavorable prognosis, the
      literature contains only sparse information of the occurrence and the prognosis
      of simultaneous PTD/ITD of these genes. We have therefore attempted to determine
      the presence and its consequence in AML and with the further aim of
      characterizing such patients with respect to other genetic aberrations and to
      prototype variables in this disease. We analyzed blast cells from 250 adult
      patients treated at the same institution during a 15-year period for FLT3 ITD and
      MLL PTD and the duplications were found in 24% and 4%, respectively. The four co
      duplicated cases (2%) did not differ with respect to sex, age, FAB-type, or
      immunophenotype, promoter methylation of p15, E-cadherin (CDH1), Estrogen
      receptor, MDR1, expression of apoptosis-related or multidrug resistance-related
      genes, though a trend toward decreased gene expression of MDR1 was observed. Two
      of the patients had a normal karyotypic analysis, while the remaining two showed
      aberrations in chromosome 11, one with trisomy 11 and the other with a der (11).
      The extensive molecular characterization of FLT3/MLL coduplicated patients
      presented here indicates that, even though they do not differ molecularly from
      the groups of patients with single ITDs, their prognosis and overall survival is
      universally poor. More patients are needed to determine whether coduplication has
      independent clinical implications compared to patients with single ITD/PTD.

PMID- 16104874
TI  - Absence of p16 and p27 gene rearrangements and mutations in de novo
      myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) represent a group of clonal hematopoietic
      disorders characterized by dyshemopoiesis and frequent evolution to acute
      leukemia. Tumor suppressor gene inactivation may be involved in MDS pathogenesis.
      The two families of cyclin-dependent kinase inhibitors (CDKIs) (INK4 family of
      p15, p16, p18 and p19 and CIP/KIP family of p21, p27 and p57) that negatively
      regulate cell cycle progression are known tumor suppressor genes. To determine
      whether genetic alterations of p16 and p27 genes play an important role in MDS
      pathogenesis, we examined DNA from 51 patients classified as 17 refractory
      anemias (RA), four refractory anemias with ringed sideroblasts (RARS), 19
      refractory anemias with an excess of blasts (RAEB), 5 refractory anemias with
      excess of blasts in transformation (RAEB-t) and 6 chronic myelomonocytic
      leukemias (CMML). Southern blot analysis detected no homozygous deletions of p16
      and p27. Polymerase chain reaction-single-strand conformation polymorphism (PCR
      SSCP) and sequencing did not reveal point mutations for both genes with the
      exception of two allelic polymorphisms, namely a C --> G transition at 447 bp of
      p16exon3 and a T --> A transition at 791 bp of p27exon1 genes. Our results
      suggest that mutations of p16 and p27 genes resulting in abnormal p16 and p27
      proteins do not represent a mechanism of gene inactivation involved in the
      pathogenesis of MDS.

PMID- 16104875
TI  - Outcome of progressive disease after autologous stem cell transplantation in
      patients with non-Hodgkin's lymphoma: a nation-wide survey.
AB  - OBJECTIVES: To analyse outcome and prognostic factors in non-Hodgkin's lymphoma
      (NHL) patients who progress after autologous stem cell transplantation (ASCT).
      PATIENTS: Altogether 115 consecutive NHL patients transplanted in 1991-2000 were
      studied. Histology included diffuse large B cell (n = 52), follicular (n = 26),
      mantle cell (n = 15), T cell (n = 16) and other subtypes (n = 6). The median time
      from ASCT to the progression was 7 months. Ninety-six patients (83%) received
      salvage treatment. RESULTS: Twenty-four patients (25%) achieved complete
      remission and 30 (31%) partial remission. The median overall survival was 8
      months (range 0-98+) and the projected 4-year survival 21%. In multivariate
      analysis factors predicting treatment response after the progression included the
      use of rituximab (P = 0.036), histology other than diffuse large B cell (P =
      0.001) and International Prognostic Index < or =2 at progression (P < 0.001).
      Normal lactate dehydrogenase (LDH) at progression (P = 0.002), response to
      salvage treatment (P < 0.001) and time from ASCT to progression > or =7 months (P
      = 0.022) were predictors for overall survival. CONCLUSIONS: Although the
      prognosis of patients who progress after ASCT is generally poor, many patients
      will respond to current therapies, and some may experience prolonged survival.
      Normal LDH at time of disease progression and longer time to progression after
      ASCT were the most powerful predictors for a promising outcome.

PMID- 16104876
TI  - The effect of ciprofloxacin on cyclophosphamide pharmacokinetics in patients with
      non-Hodgkin lymphoma.
AB  - Cyclophosphamide (CPA) is widely used in chemotherapy. The CPA is a prodrug that
      requires metabolic transformation to generate the active metabolite, 4-hydroxy
      CPA (4-OH-CPA). Ciprofloxacin (CF) is a fluoroquinolone antibiotic with a broad
      spectrum that is commonly used in treatment of a variety of infections. It has
      been reported that prophylactic administration of CF during CPA conditioning was
      a high-risk factor for relapse in patients undergoing allogeneic bone marrow
      transplantation. In the present study we investigated the pharmacokinetics of CPA
      and 4-OH-CPA in eight non-Hodgkin lymphoma (NHL) patients treated with CPA
      together with or without CF. Clearance and distribution volumes of CPA were
      significantly (P < 0.01) lower (4.7 L/h and 42.3 L, respectively) when patients
      were treated with CF prior to CPA compared to that observed when the patients did
      not receive CF (5.9 L/h and 48.1 L, respectively). No change in the elimination
      half-life was observed. The CF administration prior to CPA has resulted in
      significantly (P < 0.01) lower exposure to 4-OH-CPA as expressed as area under
      the plasma concentration curve (AUC). The metabolic ratio AUC(4-OH-CPA)/AUC(CPA)
      was lower in all patients treated with CF prior to CPA compared to that observed
      when patients received CPA only (P = 0.008). Our study showed that CF
      administration alters CPA kinetics in patients with NHL. Other antibiotics than
      these contain fluoroquinolones should be used during CPA therapy.

PMID- 16104877
TI  - Etodolac inhibits EBER expression and induces Bcl-2-regulated apoptosis in
      Burkitt's lymphoma cells.
AB  - Cyclooxygenase-2 (COX-2) is reported to be an important cellular target for
      therapy in malignancies. The growth inhibitory effects of COX-2 inhibitors on
      malignancies have been demonstrated to be through not only COX-2 dependent, but
      also independent mechanisms. In this study, we showed that etodolac, COX-2
      inhibitor, induced apoptosis via COX-2 independent pathway, and investigated the
      molecular details of etodolac-induced apoptosis in Burkitt's lymphoma cells. In
      Daudi and Raji Burkitt's lymphoma cell lines, which expressed no COX-2 enzyme,
      etodolac more strongly induced apoptosis compared to meloxicam. Moreover,
      etodolac did not induce apoptosis to normal B-lymphocytes. For the pathway of
      etodolac-induced apoptosis, reduction of anti-apoptotic bcl-2 mRNA and Bcl-2
      protein, activation of Caspase-9 and -3, down-regulation of caspase inhibitors, c
      IAP-1 and Survivin were involved. Moreover, EBER-1 and -2 expression in Epstein
      Barr virus positive Daudi and Raji cells were reduced to result in down
      regulation of Bcl-2 by treatment with etodolac. It has been reported that
      etodolac has stereoisomers, R- and S-etodolac. We found that racemate of etodolac
      more strongly induced apoptosis in Daudi and Raji cells compared to R- or S
      etodolac. In conclusion, our findings indicated etodolac inhibited EBERs
      expression and induced apoptosis via a Bcl-2-regulated pathway. Moreover,
      racemate of etodolac more effectively induced apoptosis than R- and/or S
      etodolac. Therefore, these activities of etodolac potentially extend to the
      treatment of patients with Burkitt's lymphoma resistant to chemotherapy.

PMID- 16104878
TI  - Clinicopathological analysis of T-cell lymphoma in Taiwan according to WHO
      classification: high incidence of enteropathy-type intestinal T-cell lymphoma.
AB  - OBJECTIVES: The clinicopathological characteristics of malignant lymphomas vary
      according to geography, especially for the T-cell lymphoma (TCL). The aim of this
      study is to demonstrate the incidence and clinicopathological characteristics of
      TCL in Taiwan according to WHO classification. METHODS: Archival tissue from 600
      malignant lymphomas during the period of 1995-2002 was retrieved, there were 74
      cases diagnosed with TCL. Hematoxylin and eosin slides stained and other special
      studies were reviewed. All cases were reclassified according to the WHO
      classification. Clinical data, including age, gender, clinical staging, and
      follow-up, were scrutinized. RESULTS: There were 52 males and 22 females with
      male predilectation. The incidence of TCL in malignant lymphoma was 12.3%. The
      most prevalent histologic subtype was peripheral T-cell lymphoma (PTCL), followed
      by nasal T-cell/Natural killer- (T-/NK-) cell lymphoma, T-lymphoblastic lymphoma
      (LBL), anaplastic large cell lymphoma, and enteropathy-type intestinal lymphoma
      (ETCL). Clinically, 39 cases (49%) had higher clinical stage (III/IV). Overall 2
      year and 5-year survival rate was 51.4% and 34.7%, respectively. It was
      noteworthy that ETCL had high incidence rate (8.1%) and high mortality. There was
      significant difference in survival rates in respect of clinical stages and
      histological subtypes. CONCLUSIONS: TCL is relatively less frequent in Taiwan,
      compared to other countries in Asian and western countries. The most common
      histological subtypes are PTCL, unspecified and T-/NK-cell lymphoma. Five-year
      survival rate is 34.7%. ETCL has higher incidence rate in Taiwan. The clinical
      stage and histological subtypes are prognostic parameters in determining the
      survival rates.

PMID- 16104879
TI  - Caspofungin as first line therapy of pulmonary invasive fungal infections in 32
      immunocompromised patients with hematologic malignancies.
AB  - Invasive Fungal Infections (IFI) remain a severe and major complication among
      patients with hematologic diseases, but the recent availability of new antifungal
      agents (echinocandins and new azoles) have improved the chance of cure.
      Caspofungin (Cancidas-Merck) is a large lipopeptide molecule able to inhibit the
      enzyme complex 1,3-d-glucan synthetase; this action specifically damages the
      fungal cell wall. Caspofungin (CAS) is active, in vitro and in vivo, against most
      Candida species and Aspergillus species. We report on our experience with this
      drug as first-line therapy for proven or probable pulmonary IFI in
      immunocompromised patients with hematologic malignancies. Thirty-two consecutive
      patients (20 males and 12 females, with a median age of 52 yr) have been treated
      with CAS (27 acute leukemias, 1 chronic leukemia, 3 lymphomas and 1 multiple
      myeloma). Sixteen patients (50%) had a relapsed or resistant hematologic disease,
      while 12 patients were in complete remission and 4 were at onset of disease; 8/32
      (25%) developed IFI after a hematopoietic stem cell transplant (HSCT) procedure.
      Seven out of 32 patients (22%) had a proven pulmonary IFI (7/7 Aspergillosis) and
      25 (78%) had a probable IFI with pulmonary localization as defined according to
      international consensus. Thirty-one patients (97%) had less than 1000
      granulocytes/mL at onset of infection and at the start of CAS therapy. The CAS
      was given at the dose of 70 mg on day 1, followed by 50 mg/day. Median duration
      of CAS therapy was 20 d (range 8-64); all the 31 neutropenic patients received
      concomitant granulocyte colony-stimulating factor (G-CSF). The overall response
      rate was 56% (18/32) with 12/18 complete responses and 6/18 partial responses;
      two patients (6%) had a stable disease. Twelve out of 32 (38%) did not respond
      and seven died of mycotic infection. Univariate analysis showed that granulocytes
      recovery (>500/mL vs. <500/mL) and status of hematologic disease (remission/onset
      vs. refractory/relapsed) were significantly associated to favourable outcome. No
      clinical adverse events (AE) were reported and only a grades I and II transient
      increase of serum alkaline phosphatase and/or transaminases occurred in 4/32
      (12%) patients. After CAS therapy six non-responders and six cases with a partial
      or stable response were rescued with voriconazole. Two out of six patients (33%)
      in the former group and 6/6 (100%) in the latter obtained a complete resolution
      of IFI. Our experience suggests an efficacy of CAS, in combination with G-CSF, as
      first-line treatment of proven or probable IFI with pulmonary localization. The
      drug was well tolerated and there were no significant hepatic AE even in patients
      receiving CAS with cyclosporine after a HSCT. A significant proportion of non
      responders or partial responders to CAS can be rescued with a subsequent
      voriconazole-based therapy.

PMID- 16104880
TI  - Effect of varicella zoster virus infection on bone marrow function.
AB  - BACKGROUND: Most viral infections are known to exert adverse effects on bone
      marrow function. However, certain viruses have recently been found to be
      therapeutically beneficial in the treatment of some malignant disorders. METHODS
      AND MATERIALS: A retrospective study was conducted at the Armed Forces Hospital,
      Riyadh, Saudi Arabia. The changes in the hematological parameters following
      varicella-zoster virus (VZV) infection in patients with a variety of
      hematological disorders were compared with those in a control group having the
      same spectrum of disorders and treated in the same unit over the same period of
      time but never had VZV infection. Both groups of patients received the same
      treatment protocols for their primary hematological disorders. Definitive
      treatment (DT) such as chemotherapy alone, anti-thymocyte globulin or bone marrow
      transplant was also employed in the management of patients belonging to both
      groups. RESULTS: White blood cell counts, platelet counts and hemoglobin
      concentrations in the study group started to increase 40 d after chickenpox or
      herpes zoster infection and these increases lasted for periods as long as 1050 d.
      The changes in platelet counts were more pronounced than those in other
      hematological parameters. There was a significant difference (P < 0.0001) between
      the two groups of patients in the values of platelet counts achieved between 280
      and 1050 d after DT (mean platelet count: 262 x 10(9)/L in the study group vs.
      180 x 10(9)/L in the control group, median: 288.17 x 10(9)/L in the study group
      vs. 180 x 10(9)/L in the control group, range: 102 to 415 x 10(9)/L in the study
      group vs. 26 to 365 x 10(9)/L in the control group of patients). Compared to the
      control group, the study group of patients achieved their maximum blood counts
      much earlier after DT. The maximum leucocytic count was achieved at a mean
      duration of 269.21 d in the study group and 349.61 d in the control group. The
      maximum hemoglobin level was achieved at a mean duration of 319.5 d in the study
      group and 402.6 d in the control group. The maximum platelet count was achieved
      at a mean duration of 271.4 d in the study group and 318.9 d in the control group
      of patients. CONCLUSION: VZV may behave differently from other members of the
      herpes group of viruses e.g. human cytomegalovirus and Epstein-Barr virus. Our
      observations suggest that VZV infection causes stimulation of bone marrow
      activity.

PMID- 16104881
TI  - A comparison of magnetic resonance imaging and cardiac biopsy in the evaluation
      of heart iron overload in patients with beta-thalassemia major.
AB  - OBJECTIVES: To apply magnetic resonance imaging (MRI) for the assessment of
      myocardial iron deposition in patients with beta-thalassemia and compare the
      results with cardiac biopsy data. BACKGROUND: Myocardial iron accumulation is the
      main cause for cardiac complications in beta-thalassemia. METHODS: Twenty-five
      consecutive thalassemic patients were studied using a 0.5-T (Tesla) system, ECG
      gated, with echo time (TE) = 17-68 ms. T2 relaxation time of the interventricular
      septum was calculated assuming simple monoexponential decay. A heart T2
      relaxation time value of 32 ms was used for the discrimination between high and
      low iron deposition. Heart biopsy was performed within a week after the MRI
      study. Patients with stainable iron in more than 50% of the myofibrils were
      graded as having severe iron deposition. A serum ferritin level below 2000 ng/mL
      was considered as an indication of successful chelation. RESULTS: Seven of the 25
      patients had heart biopsy indicative of low iron deposition (Group L) and the
      remaining 18 patients had heart biopsy indicative of high iron deposition (Group
      H). T2 relaxation time of the heart (T2H) was lower in Group H compared to Group
      L (31.5 +/- 3.9 (range: 28-40) ms vs. 35.7 +/- 3.7 (range: 29-40) ms, P = 0.026).
      The T2H was in agreement with heart biopsy in 86% of the patients in Group L and
      in 78% of the patients in Group H (overall agreement 80%). Similarly, serum
      ferritin levels were in agreement with heart biopsy in 28% and 88%, respectively
      (overall agreement 72%). In Group L, MRI was in better agreement with biopsy
      compared to serum ferritin (86% vs. 28%, P < 0.05). A receiver operating
      characteristic curve (ROC) analysis confirmed that a T2 relaxation time of 32 ms
      had the highest discriminating ability for the corresponding biopsy outcome.
      CONCLUSIONS: Heart T2 relaxation time appears in agreement with cardiac biopsy,
      both in high and low iron deposition, and may become a useful non-invasive index
      in beta-thalassemia.

PMID- 16104882
TI  - Platelet and granulocyte alloimmunisation in multitransfused Tunisian patients.
AB  - We determined the frequency of post-transfusion alloimmunisation against platelet
      and granulocyte antigens in 51 Tunisian polytransfused patients with
      haematological diseases. Serum samples were analysed by a standard and an
      antiglobulin-augmented lymphocytotoxicity technique, a granulocyte agglutination
      test, a granulocyte immunofluorescence test, a platelet immunofluorescence test
      and the monoclonal antibody-specific immobilisation of platelet antigens assay.
      No granulocyte-specific antibodies were detected. HLA antibodies were found in
      58.8% of patients. Platelet-specific antibodies were detected in four patients
      and were directed against human platelet antigen (HPA)-5b, HPA-1b and HPA-3a. The
      three patients with Glanzmann's thrombasthenia developed anti-GPIIb/IIIa
      antibodies. This study provides immunogenetic information that could improve the
      management of transfusion therapy in Tunisia.

PMID- 16104883
TI  - Haemorheology in Gaucher disease.
AB  - In Gaucher disease, a deficiency of glucocerebrosidase results in the
      accumulation of glucocerebroside within the lysosomes of the monocyte-macrophage
      system. Prior to the availability of enzyme replacement therapy (ERT),
      splenectomy was often indicated for hypersplenism. Haemorheological abnormalities
      could be expected in view of the anaemia and abnormal lipid metabolism in these
      patients and the role of the spleen in controlling erythrocyte quality.
      OBJECTIVES: To investigate the effect of Gaucher disease on blood and plasma
      viscosity, erythrocyte aggregation and erythrocyte deformability, and to
      determine whether observed rheological differences could be attributed to
      splenectomy. METHODS: Haematological and haemorheological measurements were made
      on blood collected from 26 spleen-intact patients with Gaucher disease, 16
      splenectomised patients with Gaucher disease, 6 otherwise healthy asplenic non
      Gaucher disease subjects and 15 healthy controls. RESULTS: No haemorheological
      differences could be demonstrated between spleen-intact patients with Gaucher
      disease and the control group. Compared to controls, both asplenic Gaucher
      disease and asplenic non-Gaucher disease study groups had a reduced MCHC (P =
      0.003 and 0.005, respectively) and increased whole blood viscosity at 45%
      haematocrit (Hct), relative viscosity and red cell aggregation index - all
      measured at low shear (P < 0.05 for all). Additionally, asplenic patients with
      Gaucher disease alone showed an increased MCV (P = 0.006), an increased whole
      blood viscosity at 45% Hct measured at high shear (P = 0.019), and a reduced
      relative filtration rate (P = 0.0001), compared to controls. CONCLUSION: These
      observations demonstrate a direct and measurable haemorheological abnormality in
      Gaucher disease only revealed when there is no functioning spleen to control
      erythrocyte quality.

PMID- 16104884
TI  - Hemoglobin H hydrops fetalis syndrome resulting from the association of the - 
      SEA deletion and the alphaQuong Szealpha mutation in a Chinese woman.
AB  - A case with Hb H hydrops fetalis syndrome resulting from the association of the -
      -(SEA) deletion and the alpha(Quong Sze)alpha mutation is reported. This is the
      first description of Hb H hydrops associated with the Hb Quong Sze mutation.

PMID- 16104885
TI  - Philadelphia-chromosome positive thrombocythemia in a child.
AB  - Philadelphia-chromosome positive thrombocythemia without features of chronic
      myeloid leukemia in peripheral blood has been described in adults. It is rare in
      children. We present a case of Philadelphia positive thrombocythemia in a child
      who was managed with a combination of imatinib and hydroxyurea. Although a
      reduction in the BCR-ABL transcript was documented, the thrombocytosis was
      refractory to imatinib alone and required the addition of hydroxyurea.

PMID- 16104886
TI  - Transition of polycythemia vera to chronic myeloid leukaemia.
AB  - A 77-year-old female with polycythemia vera (PV) showed a sudden, typical chronic
      myeloid leukaemia (CML), 8 yr after the initial diagnosis, and an intermittent
      treatment with hydroxyurea (0.5-1 g/d) and phlebotomies. At PV diagnosis, the Ph
      chromosome was negative and no bcr-abl rearrangement was observed; they were both
      revealed positive at CML onset. Transition of PV to CML is very rare; only seven
      substantiated cases had been reported in the literature up until now (six from
      1964 to 1993). All patients but one received (32)P or alkylating agents for PV
      treatment. The pathogenetic mechanisms are briefly discussed.

PMID- 16104887
TI  - Treatment with hydroxyurea and iron chelation therapy in patients with
      hemoglobinopathies.

PMID- 16104890
TI  - The regulatory functions of Ly-49A, Ly-49D and Ly-49G2 on NK cells in the
      recognition and rejection of the alloantigen in vivo.
AB  - Ly-49A is an inhibitory receptor that binds H-2Dd and H-2Dk. The downregulation
      of Ly-49A is thought to mediate NK self tolerance in vivo. In this study, we
      analyzed the regulation of Ly-49A, D and G2 on NK cells in an in vivo rejection
      model. After injection with 1 x 10(8) B10.D2 spleen cells (SC) into B 10 mice, we
      found Ly-49A downregulated within 3 h on NK cells of B10 mice, whereas
      expressions of Ly-49D and G2 were augmented. To investigate effects of different
      expression patterns of Ly-49 receptors on NK cells, Ly-49A, D or G2-depleted B10
      mice were inoculated with B10.D2 SC. NK cells from SC of Ly-49A-depleted and
      B10.D2 SC-injected B10 mice showed enhanced cytotoxicity to Dd-positive targets
      in vitro. Furthermore, reduced numbers of B10.D2 SC were observed in Ly-49A or G2
      depleted B10 mice, whereas increased numbers of B10.D2 SC were observed in Ly-49D
      depleted B10 mice after inoculation with B10.D2 SC in vivo. These findings
      indicated that the downregulation of Ly-49A and the augmentation of Ly-49D
      expression may mediate NK cells to recognize and kill Dd antigen efficiently. In
      conclusion, each Ly-49 isoform may play independent roles in the regulation of
      activation or inhibition on NK cells.

PMID- 16104891
TI  - Testosterone replacement therapy in hypogonadal men and prostate cancer risk.

PMID- 16104892
TI  - Penile length changes after radical prostatectomy.

PMID- 16104893
TI  - Non-myeloablative allogeneic stem cell transplantation: a promising new therapy
      in the management of metastatic renal cell cancer.

PMID- 16104894
TI  - Scrotal ultrasonography in the urology clinic.

PMID- 16104895
TI  - A perspective on protein profiling of blood.

PMID- 16104896
TI  - Adjuvant therapy of renal cell carcinoma: patient selection and therapeutic
      options.

PMID- 16104897
TI  - Microsatellite instability and transitional cell carcinoma of the upper urinary
      tract.

PMID- 16104898
TI  - Orthotopic neobladder reconstruction--what are the options?

PMID- 16104899
TI  - Delayed graft function: a dilemma in renal transplantation.

PMID- 16104900
TI  - Clinical outcomes of androgen deprivation as the sole therapy for localized and
      locally advanced prostate cancer.
AB  - OBJECTIVE: To characterize the clinical outcomes of androgen deprivation therapy
      (ADT) as the sole therapy for localized prostate cancer, and to determine
      independent predictors of disease progression, as recent studies indicate an
      increasing use of ADT. PATIENTS AND METHODS: The records of all patients with cT1
      4NXM0 adenocarcinoma of the prostate treated with ADT as the primary initial
      therapy at the Portland Veterans Affairs Medical Center between 1993 and 2000
      were reviewed. Age, race, Charlson Health Index, family history, prostate
      specific antigen (PSA) level, PSA density, digital rectal examination (DRE)
      findings, Gleason score, and percentage of positive biopsy cores at diagnosis
      were recorded for 81 patients. Patients had a median (SD, range) age of 73 (5.6,
      58-84) years, a PSA level of 14.3 (34.6, 1.4-252) ng/mL and tumours were
      classified as Gleason score < or = 5 in 9% of patients, 6 in 31%, 7 in 31% and 8
      10 in 30%. Outcomes extracted were PSA progression, PSA nadir, bone fractures,
      local progression, distant progression and overall survival. RESULTS: With a
      median (range) follow-up of 54 (6-115) months, the incidence of local
      progression, distant progression, bone fractures, PSA progression, and death were
      10%, 7%, 25%, 21% and 41% respectively. The percentage of positive biopsy cores >
      or = 83%, age < 70 years, Gleason score > or = 7, abnormal DRE, and PSA nadir >
      or = 0.2 ng/mL were significantly associated with PSA progression by univariate
      analysis. The multivariate analysis identified age < 70 years (hazard ratio 6.52,
      95% confidence interval 2.29-18.55) and Gleason score > or = 6 (4.0, 2.0-12.0) as
      independent risk factors for PSA progression. CONCLUSIONS: ADT resulted in modest
      control of localized prostate cancer, but younger patients and those with Gleason
      > or = 6 cancers were at higher risk of treatment failure. Toxicity, principally
      in the form of bone fractures, was high.

PMID- 16104901
TI  - ASCENT: the androgen-independent prostate cancer study of calcitriol enhancing
      taxotere.
AB  - ASCENT, the Androgen-Independent Prostate Cancer (AIPC) Study of Calcitriol
      Enhancing Taxotere, is a double-blind, placebo-controlled randomized clinical
      trial designed to determine if DN-101, a high-dose oral formulation of calcitriol
      designed for cancer therapy, significantly increases the proportion of patients
      who have > 50% reduction in serum prostate-specific antigen (PSA) levels in
      response to docetaxel. The secondary goals of ASCENT are to evaluate the effect
      of DN-101 combined with docetaxel on PSA progression-free survival, tumour
      response rate in measurable disease, tumour progression-free survival, skeletal
      morbidity-free survival, clinical progression-free survival, and overall
      survival, and to examine the safety and tolerability of DN-101 combined with
      docetaxel. ASCENT builds on phase I work showing that weekly dosing allows
      substantial dose-escalation of calcitriol, the natural ligand for the vitamin D
      receptor, and on phase II work that suggested that adding weekly high-dose
      'pulse' calcitriol may enhance the activity of weekly docetaxel in patients with
      AIPC. The preclinical rationale for calcitriol and its combination with docetaxel
      for prostate cancer therapy is reviewed, as are the key clinical trials that led
      to the development of ASCENT. The ASCENT design and its strengths and limitations
      are presented.

PMID- 16104902
TI  - Long-term side-effects of intermittent androgen suppression therapy in prostate
      cancer: results of a phase II study.
AB  - OBJECTIVE: To assess the feasibility and tolerability of intermittent androgen
      suppression therapy (IAS) in prostate cancer. PATIENTS AND METHODS: Patients with
      recurrent or metastic prostate cancer received cyclical periods of treatment with
      leuprolide acetate and nilutamide for 8 months, and rest periods. Cycles were
      repeated at progression until the treatment failed to achieve normal prostate
      specific antigen (PSA) levels. Patients were followed with PSA level,
      testosterone level, haemoglobin level, weight and bone mineral density
      evaluations. The median time to treatment failure, recovery from anaemia, or
      normalization of testosterone level was estimated by the Kaplan-Meier method.
      RESULTS: In all, 95 patients received 245 cycles; the median duration of rest
      periods was 8 months and median time to treatment failure 47 months. Testosterone
      recovery during rest periods was documented in 117 (61%) of cycles. Anaemia was
      mild and reported in 33%, 44% and 67% of cycles 1, 2 and 3, respectively. Sexual
      function recovered during the rest periods in 47% of cycles. There was no
      significant overall change in body mass index at the end of the treatment period.
      Osteoporosis was documented in at least one site evaluated in 41 patients (37%).
      CONCLUSIONS: IAS has the potential to reduce side-effects, including recovery of
      haemoglobin level, return of sexual function and absence of weight gain at the
      end of the study period.

PMID- 16104903
TI  - Clinical utility of human glandular kallikrein 2 within a neural network for
      prostate cancer detection.
AB  - OBJECTIVE: To assess, using artificial neural networks (ANNs), human glandular
      kallikrein 2 (hK2), prostate-specific antigen (PSA), and percentage free/total
      PSA (f/tPSA), for discriminating between prostate cancer and benign prostatic
      hyperplasia (BPH). MATERIAL AND METHODS: Serum samples from 475 patients with
      prostate cancer (n = 347) or BPH (n = 128) within the PSA range of 1-20 ng/mL
      were analysed for tPSA, fPSA and hK2 (research assay, Toronto, Canada). Data were
      analysed in the ranges of 1-4, 2-4, 4-10, and 2-20 ng/mL tPSA. Back-propagation
      ANN models with the variables PSA, f/tPSA, and hK2, hK2/fPSA and hK2/(f/tPSA)
      were constructed. The diagnostic validity was evaluated by receiver-operating
      characteristic (ROC) curve analysis. RESULTS: Whereas the median concentration of
      hK2 was not significantly different between patients with BPH or prostate cancer
      in any of the tPSA ranges, the f/tPSA, hK2/fPSA and hK2/(f/tPSA), and the hK2
      based ANN outputs were always significantly different between patients with
      prostate cancer or BPH. Using ROC curve comparison, all variables were
      significantly better than hK2 in all ranges. The hK2-based ANN performed better
      than f/tPSA except in the 4-10 ng/mL tPSA range. At 90% and 95% sensitivity, the
      hK2-based ANN was also significantly better than f/tPSA in the 1-4 ng/mL tPSA
      range. hK2/(f/tPSA) achieved equal results to the hK2-based ANN except in the
      range 2-20 ng/mL tPSA. CONCLUSIONS: The hK2-based ANN improves the outcome of
      f/tPSA but not hK2/(f/tPSA) in almost all analysed subgroups. When comparing the
      results at 90% and 95% sensitivity the hK2-based ANN only performed significantly
      better than f/tPSA in the lowest tPSA range. Only in lower tPSA ranges do hK2
      based ANNs show an advantage for further improving prostate cancer detection.

PMID- 16104904
TI  - A comparison of the biological features between prostate cancers arising in the
      transition and peripheral zones.
AB  - OBJECTIVES: To investigate differences in the biological features of prostate
      cancer according to the zonal origin. PATIENTS AND METHODS: Among 172 consecutive
      patients who had a radical prostatectomy (RP), the study included 124 diagnosed
      as having either transition zone (TZ) or peripheral zone (PZ) cancer, defined
      according to whether there was > 70% of the cancer area in the TZ or PZ,
      respectively. The clinicopathological features were then compared between these
      groups. In addition, the RP specimens were stained immunohistochemically with
      antibodies to Ki-67, Bcl-2, matrix metalloproteinase-2 (MMP-2), MMP-9 and
      vascular endothelial growth factor (VEGF). RESULTS: Twenty-four patients were
      diagnosed as having TZ cancer and the remaining 100 as having PZ cancer. Prostate
      specific antigen (PSA) values in patients with TZ cancer were significantly
      higher than in those with PZ cancer. Tumour volume in TZ cancer was significantly
      greater than that in PZ cancer, but there was no significant difference in
      biochemical recurrence-free survival between the groups. Immunohistochemistry
      showed that despite there being no differences in Bcl-2 and VEGF expression
      between TZ and PZ cancers, there was significantly greater expression of Ki-67,
      MMP-2 and MMP-9 in PZ than TZ cancers. CONCLUSIONS: Despite there being no
      significant difference in biochemical recurrence-free survival after RP between
      patients with TZ and PZ cancers, there was less cell proliferation and biomarker
      levels related to invasive potential in TZ than in PZ cancers.

PMID- 16104905
TI  - Local steroid application during nerve-sparing radical retropubic prostatectomy.
AB  - OBJECTIVE: To evaluate the effect on potency rates after surgery of applying
      local steroids to the neurovascular bundles (NVBs) of the prostate after
      bilateral nerve-sparing radical retropubic prostatectomy (BNS-RRP). PATIENTS AND
      METHODS: Sixty potent men undergoing BNS-RRP for clinically localized prostate
      cancer were prospectively randomized equally into two groups. In group 1, 10 mL
      of betamethasone cream 0.1% was applied locally to both NVBs, and group 2 had
      only the usual BNS-RRP with no corticoid cream. Complications and potency were
      evaluated at 3, 6 and 12 months in all patients and compared between the groups.
      RESULTS: At 12 months, 57% and 60% of patients were potent in group 1 and 2,
      respectively; the respective mean International Index of Erectile Function (5
      item) scores were 14.76 and 15.43 (P = 0.59). Potency rates at 3, 6 and 12 months
      were not significantly different between the groups, and the continence rates at
      12 months were also similar, with 93% and 90% of patients in groups 1 and 2 being
      continent, respectively. Ten and five patients in groups 1 and 2, respectively,
      required a blood transfusion (P = 0.23). There were no fistulae, wound dehiscence
      or rectal perforations. One patient in group 2 presented 4 months after RRP with
      a bladder neck contracture. CONCLUSIONS: Local application of betamethasone does
      not improve or expedite the recovery of erectile function after BNS-RRP, but
      there were no complications associated with its use.

PMID- 16104906
TI  - A lower dose of thalidomide is better than a high dose in metastatic renal cell
      carcinoma.
AB  - OBJECTIVE: To conduct a dose-finding trial using a single low dose and dose
      escalation of a higher dose of thalidomide in patients with metastatic renal cell
      carcinoma (RCC), and to evaluate the antineoplastic effectiveness of thalidomide
      as an anti-angiogenic agent on RCC. PATIENTS AND METHODS: The 14 patients
      enrolled in the study had progressive measurable metastatic RCC and consented to
      participate. Patients were randomized to either a fixed low dose of 200 mg of
      thalidomide or to a high dose of 800 mg that was increased to a maximum dose of
      1200 mg daily. Patients were evaluated for response after 8 weeks of therapy.
      RESULTS: Stable disease was achieved in six patients and was seen in both the low
      dose and high-dose thalidomide groups. The median overall survival was 9 months.
      The low-dose thalidomide regimen was better tolerated and patients survived
      longer than those on the high-dose regimen (16 vs 6 months, P = 0.04) CONCLUSION:
      The use of low-dose thalidomide in patients with metastatic RCC was well
      tolerated and they survived for longer than those on the high-dose regimen.

PMID- 16104907
TI  - Assessing regional hypoxia in human renal tumours using 18F-fluoromisonidazole
      positron emission tomography.
AB  - OBJECTIVE: To assess renal tumours for hypoxic regions using 18F
      fluoromisonidazole (18F-FMISO) positron emission tomography (PET), a recognized
      noninvasive method for detecting hypoxia in tumours, as renal cell carcinoma
      (RCC) can be potentially cured with nephrectomy but recurrence develops in most
      patients, who then respond poorly to treatments such as chemotherapy, and hypoxia
      is known to confer resistance to radiotherapy and chemotherapy in many solid
      tumours. PATIENTS AND METHODS: In all, 17 patients had 18F-FMISO PET scans before
      nephrectomy for presumed RCC. Specimens were examined histologically, and
      immunohistochemistry was used to compare the microvessel density (MVD) as an
      indicator of angiogenesis in the tumour and normal parenchyma, in 15 patients.
      Tumour oxygenation was measured invasively in three patients using a
      polarographic oxygen sensor probe. RESULTS: Of the 15 patients with histological
      results, 11 had RCC and four had other tumours. Although there was a trend there
      was no statistically significant (P = 0.14) difference in the maximum
      standardized uptake value (SUV(max)) when comparing the region of the kidney
      involved with RCC; the mean (95% confidence interval) SUV(max) in the tumours was
      1.3 (0.15), whilst that in the normal contralateral kidney was 1.1 (0.22). The
      MVD was greater in RCC, at 13.7 (3.1) mean vessels per high-power field than in
      normal tissue, at 6.9 (1.9). Hypoxia as measured polarographically was detected
      in three RCCs (median pO2 9.6 mmHg) compared to normal parenchyma at 37.6 mmHg.
      CONCLUSIONS: Although 18F-FMISO scans showed significant uptake in other solid
      tumours, there was only mild 18F-FMISO uptake in the present RCCs. The invasive
      measurements indicated that there was hypoxia in RCC, but the median pO2 did not
      fall below 9.5 mmHg. Further direct studies of renal tumour oxygenation combined
      with therapies directed towards hypoxia may allow a better understanding of the
      relationship between 18F-FMISO results and the biological significance of hypoxia
      in RCC.

PMID- 16104908
TI  - Epstein-Barr virus infection in sarcomatoid renal cell carcinoma tissues.
AB  - OBJECTIVE: To determine whether Epstein-Barr virus (EBV) infection is related to
      renal cell carcinoma (RCC) tissues. MATERIALS AND METHODS: We investigated EBV
      infection and its genotypes in 73 cases of different types of RCC and 18 of non
      neoplastic kidney. EBV infection and its genotypes were determined by EBV-encoded
      RNAs in situ hybridization (EBER-ISH) and polymerase chain reactions for EBV
      encoded nuclear antigen 1 (EBNA-1) and EBNA-3C. The immunophenotype and EBV
      status of the EBV-infected cells were examined by double-labelling of EBER-ISH
      and/or immunohistochemistry for lymphoid cell markers, EBV proteins, and CD21.
      RESULTS: EBER-ISH signals were detected in five of 73 RCC tissues (6.8%), but in
      none of 18 non-neoplastic kidneys. Interestingly, EBER-ISH was positive only in
      five of the 10 sarcomatoid RCCs, and of these, four also showed amplification of
      EBNA-1. EBV was located exclusively in the tumour-infiltrating B lymphocytes of
      sarcomatoid RCCs. The genotype of EBV was determined as type 1. A few EBV
      infected B cells expressed BZLF1 (an EBV immediate-early gene product) while none
      expressed EBNA-2 or latent membrane protein 1. This indicates that the B cells
      are of EBV latency type I, often replicating EBV. EBV infection did not affect
      the survival rates of patients with sarcomatoid RCC (P = 0.635, Kaplan-Meier
      analysis, log-rank test). CONCLUSION: EBV is present only in tumour-infiltrating
      B lymphocytes of sarcomatoid RCCs. The present study suggests that sarcomatoid
      RCC modulates a function of EBV-specific T cells controlling EBV replication, or
      stimulates differentiation of memory B cells into plasma cells.

PMID- 16104909
TI  - Detection of human telomerase RNA in the tumour-surrounding mucosa of bladder
      carcinomas as a marker for premalignant transformation.
AB  - OBJECTIVES: To investigate tumour tissue and non-malignant tumour-surrounding
      bladder mucosa (NTSBM) for expression of human telomerase RNA (hTR) as a possible
      marker for premalignant transformation of urothelial cells. MATERIAL AND METHODS:
      From 67 patients with superficial transitional cell carcinoma (TCC), sections
      with representative tumour tissue and NTSBM were selected for evaluation.
      Sections with moderate or severe dysplasia were omitted from evaluation. hTR
      expression was detected with in situ hybridization using a 35S-UTP-labelled
      riboprobe, and analysed semiquantitatively by counting the hybridization signals.
      RESULTS: In 45 of the 67 patients hTR expression was moderate or strong in tumour
      tissue, and in 20 hTR expression was moderate or strong in NTSBM. Moderate or
      strong hTR expression was detected in the NTSBM from 19 of 60 patients with
      pTa/pT1 tumours. Of the 56 patients who were treated conservatively, eight had
      tumour recurrence, of whom five had moderate or strong hTR expression in the
      TSBM, compared with only 14 of 48 patients without tumour recurrence. CONCLUSION:
      Detecting hTR expression and the morphological distribution of hTR hybridization
      signals in NTSBM by in situ hybridization might indicate premalignant alterations
      involved in tumour recurrence.

PMID- 16104910
TI  - A case-control study of risk factors in men with chronic pelvic pain syndrome.
AB  - OBJECTIVE: To compare the demographic, behavioural, clinical and medical history
      characteristics of men with chronic prostatitis/chronic pelvic pain syndrome
      (CP/CPPS) and asymptomatic controls, to identify characteristics that might be
      associated with this syndrome. PATIENTS AND METHODS: Self-administered
      epidemiological questionnaires were completed by 463 men with CP/CPPS and 121
      asymptomatic age-matched controls. We compared the prevalence of possible risk
      factors between men with CP/CPPS and controls, using generalized Mantel-Haenszel
      tests, and developed multivariate predictive models using logistic regression
      methods, adjusting for clustering by clinical centre within both methods.
      RESULTS: Compared to controls, men with CP/CPPS reported a significantly greater
      lifetime prevalence of nonspecific urethritis (12% vs 4%, P = 0.008),
      cardiovascular disease (11% vs 2%, P = 0.004), neurological disease (41% vs 14%,
      P < 0.001), psychiatric conditions (29% vs 11%, P < 0.001), and haematopoietic,
      lymphatic or infectious disease (41% vs 20%, P < 0.001). CONCLUSION: A wide range
      of self-reported medical conditions was associated with CP/CPPS. Further studies
      are necessary to determine whether they play a role in the pathogenesis of
      CP/CPPS.

PMID- 16104911
TI  - The economic impact of using alfuzosin 10 mg once daily in the management of
      acute urinary retention in the UK: a 6-month analysis.
AB  - OBJECTIVE: To calculate the economic consequences of using alfuzosin 10 mg once
      daily for managing acute urinary retention (AUR) related to benign prostatic
      hyperplasia (BPH). METHODS: We examined whether alfuzosin use during
      hospitalization for AUR and for 6 months after a successful trial without
      catheter (TWOC) is cost effective compared to placebo and immediate
      prostatectomy, from the perspective of patients managed in the National Health
      Service (NHS) in the UK. A decision-analysis model was developed to estimate the
      costs of various treatment options within the first 6 months after a first
      episode of AUR. Clinical data were obtained from a large randomized clinical
      trial comparing alfuzosin 10 mg with placebo, and from published reports. Cost
      data were obtained from both NHS and resource-use data gathered during the
      clinical trial. A Monte Carlo analysis, allowing variability in all uncertain
      variables of the model, was used to calculate the uncertainty surrounding the
      results. RESULTS: Treating patients with alfuzosin during initial hospitalization
      for AUR and in the first 6 months after a successful TWOC generates a cost-saving
      of pounds 349 relative to placebo. Savings related to immediate prostatectomy
      were pounds 892; both savings were significant (P < 0.05). Alfuzosin treatment
      was associated with a lower rate of prostatectomy after discharge from hospital
      after a successful TWOC. CONCLUSION: Treatment with alfuzosin 10 mg once daily
      before and after a successful TWOC has both clinical and economic benefits. It
      decreases the need for emergency surgery for BPH and reduces treatment costs in
      the first 6 months.

PMID- 16104912
TI  - Long-term sustained improvement in symptoms of benign prostatic hyperplasia with
      the dual 5alpha-reductase inhibitor dutasteride: results of 4-year studies.
AB  - OBJECTIVE: To report additional analyses of efficacy over the initial 2 years and
      during a 2-year open-label extension of the three pivotal phase 3 studies in
      which dutasteride, a dual inhibitor of type 1 and 2 5alpha-reductase, was shown
      to be effective and well tolerated. PATIENTS AND METHODS: All patients in the
      placebo and active groups were eligible for entry into the 2-year open-label
      extension, with all receiving dutasteride 0.5 mg daily. Mean changes from
      baseline were calculated for the American Urologic Association Symptom Index (AUA
      SI) score at each scheduled time in the double-blind and open-label phase. The
      additional analyses included a breakdown of the AUA-SI score, including
      stratifying patients by symptom severity, assessment by baseline age and prostate
      volume, and the evaluation of symptoms responders. RESULTS: There was a
      clinically meaningful improvement in AUA-SI in patients on dutasteride in the
      double-blind phase, but not in those on placebo. At 48 months, patients on
      dutasteride in both study phases had greater improvements in AUA-SI score and
      individual question scores than those on dutasteride in the open-label phase
      only. The proportion of patients with severe symptoms declined in both study
      groups, although these changes were more profound in those receiving dutasteride
      for the 4-year duration of the study. CONCLUSION: In men with symptomatic benign
      prostatic hyperplasia, long-term (4-year) treatment with the dual isozyme 5alpha
      reductase inhibitor dutasteride resulted in sustained and continued improvements
      in symptoms and flow rate. For 4 vs 2 years, longer dutasteride therapy resulted
      in greater symptom improvement.

PMID- 16104913
TI  - Ease of removal of thermo-expandable prostate stents.
AB  - OBJECTIVE: To report the ease of removal of the Memokath 028 prostatic stent
      (Engineers & Doctors A/S, Hornbaek, Denmark), an important attribute of the
      'ideal' prostatic stent. PATIENTS AND METHODS: Data on patients who had had a
      Memokath 028 stent removed in three different centres in Europe over an 8-year
      period were collected retrospectively. Standardized forms were used to record
      relevant information from each physician's patient files. RESULTS: Ninety-three
      patients had their stents removed at the three reporting centres; the mean
      indwelling time of their stent was 12.9 months, and most stents were inserted for
      symptomatic benign prostate disease. Reasons for removal included recurrent
      outlet or storage-type urinary symptoms, migration of the stent, stent-related
      pain, recurrent urosepsis and detrusor failure. The stents were removed on a day
      case basis in 32% of patients. Topical anaesthesia or no anaesthesia was used in
      48%. Of these patients, only 9% described moderate discomfort or worse. The
      procedure took a mean of 11 min and was felt to be easy or fairly easy in 90% of
      patients. CONCLUSIONS: These data show the ease of removal of the Memokath 028
      stent, reinforce its overall success in achieving the requirements of the ideal
      intraprostatic stent, and further emphasize the advantages of this implant over
      the epithelializing, permanent intraprostatic stent.

PMID- 16104914
TI  - Comparison of tamsulosin and naftopidil for efficacy and safety in the treatment
      of benign prostatic hyperplasia: a randomized controlled trial.
AB  - OBJECTIVES: To compare the efficacy and safety of two alpha1a/alpha1d
      adrenoceptor (AR) antagonists with different affinity for the alpha1AR subtypes,
      tamsulosin and naftopidil, in the treatment of benign prostatic hyperplasia
      (BPH). PATIENTS AND METHODS: Patients with BPH were randomized to receive either
      tamsulosin or naftopidil. The primary efficacy variables were the changes in the
      total International Prostate Symptom Score (IPSS), maximum flow rate on free
      uroflowmetry, and residual urine volume. The secondary efficacy variables were
      average flow rate, changes in the IPSS storage score, IPSS voiding score, and
      quality-of-life (QoL) Index score, from baseline to endpoint (12 weeks). Data on
      all randomized patients were included in the safety analyses for adverse effects
      and changes in blood pressure. RESULTS: Of the 185 patients enrolled data for 144
      who were eligible for inclusion in the efficacy analysis were analysed (75 from
      the tamsulosin and 69 from the naftopidil group). There was no significant
      difference in any variable at baseline between the groups. There were
      statistically significant improvements for all primary and secondary variables in
      both groups, except for residual urine in the tamsulosin group. However, there
      was no significant intergroup difference in the improvement of any efficacy
      variable between the groups. The adverse effects were comparable, with no
      significant differences in systolic and diastolic blood pressure after treatment
      in both groups. CONCLUSIONS: This study suggests that naftopidil is as effective
      and safe as tamsulosin. Both drugs were effective in improving storage and
      voiding symptoms. However, there was no difference in clinical efficacy or
      adverse effects between the alpha1 AR antagonists with different affinity to
      alpha1 subtypes, alpha1a and alpha1d.

PMID- 16104915
TI  - Treatment of incontinence after prostatectomy using a new minimally invasive
      device: adjustable continence therapy.
AB  - OBJECTIVE: To evaluate the safety and efficacy of a new minimally invasive
      urological implant for incontinence after prostatectomy. PATIENTS AND METHODS:
      The adjustable continence therapy device (ProACT, Uromedica, Plymouth, MN, USA)
      consists of two balloons placed via a perineal approach bilaterally at the
      bladder neck in patients after prostatectomy. Titanium ports, attached via
      discrete tubing to each balloon, are placed in the scrotum, allowing for separate
      volume adjustments of the balloons at any time during and after surgery. Changes
      in a quality-of-life questionnaire (I-QoL), pad usage and a subjective continence
      grading score were assessed in 117 consecutive men after implanting the Pro-ACT,
      at baseline and at 1, 3, 6, 12 and 24 months. RESULTS: After a mean (range)
      follow-up of 13 (3-54) months and with a mean of 3 (0-15) adjustments, 67% of men
      were dry, using at most one 'security' pad daily; 92% were significantly
      improved, and 8% showed no improvement. The I-QoL score improved from a median of
      34.7 to 66.3 after 2 years (42 men; P < 0.001), the daily pad count decreased
      from a mean of 6 (1-24)/day to 1 (0-6)/day at 2 years (P < 0.001). Continence
      achieved at < or = 6 months after implantation through incremental adjustment
      remained durable at > or = 2 years in most patients. There were complications
      during and after surgery in 54 patients, mostly minor and decreasing with
      increasing expertise, primarily reflecting the development and refinement of the
      new surgical technique and its instrumentation. Re-implantation for complications
      was required in 32 patients, with a 75% success rate. CONCLUSIONS: The ProACT
      peri-urethral prosthesis produces durable outcomes equivalent or better than
      other minimally invasive treatments for incontinence after prostatectomy. Its
      unique design allows for easy adjustment after surgery to achieve the desired
      urethral resistance, with no further surgical intervention, thus allowing for an
      optimum balance between voiding pressures and continence. The promising results
      reported here suggest that this may be an appropriate, effective and durable
      first-line treatment to offer men with stress urinary incontinence after
      prostatectomy.

PMID- 16104916
TI  - Pelvic floor exercises for erectile dysfunction.
AB  - OBJECTIVE: To examine the role of pelvic floor exercises as a way of restoring
      erectile function in men with erectile dysfunction. PATIENTS AND METHODS: In all,
      55 men aged > 20 years who had experienced erectile dysfunction for > or = 6
      months were recruited for a randomized controlled study with a cross-over arm.
      The men were treated with either pelvic floor muscle exercises (taught by a
      physiotherapist) with biofeedback and lifestyle changes (intervention group) or
      they were advised on lifestyle changes only (control group). Control patients who
      did not respond after 3 months were treated with the intervention. All men were
      given home exercises for a further 3 months. Outcomes were measured using the
      International Index of Erectile Function (IIEF), anal pressure measurements and
      independent (blinded) assessments. RESULTS: After 3 months, the erectile function
      of men in the intervention group was significantly better than in the control
      group (P < 0.001). Control patients who were given the intervention also
      significantly improved 3 months later (P < 0.001). After 6 months, blind
      assessment showed that 40% of men had regained normal erectile function, 35.5%
      improved but 24.5% failed to improve. CONCLUSION: This study suggests that pelvic
      floor exercises should be considered as a first-line approach for men seeking
      long-term resolution of their erectile dysfunction.

PMID- 16104917
TI  - Prospective analysis of outcomes after microsurgical intussusception
      vasoepididymostomy.
AB  - OBJECTIVE: To prospectively analyse the outcomes of microsurgical
      vasoepididymostomy using the intussusception technique, as vasoepididymostomy is
      considered the most challenging reconstructive microsurgery in urology. PATIENTS
      AND METHODS: From 1998 to 2003, of 324 men with obstructive azoospermia who had
      undergone microsurgical reconstruction of the reproductive tracts, 68 (21%) had
      intussusception vasoepididymostomy bilaterally or unilaterally in a functionally
      solitary testis. The outcomes of these patients were analysed prospectively.
      RESULTS: The mean age was 39.8 years for the men and 31.8 years for their
      partners. The causes of obstruction were after vasectomy in 31%, infection in
      22%, iatrogenic in 19%, trauma in 1.5%, and idiopathic in 27%. The median
      duration of obstruction was 18.8 years; 37% of patients had had previous failed
      attempts at reconstruction. The mean (range) follow-up was 15.2 (1-36) months.
      The overall patency (>10 000 sperm/mL) rate was 84% (53/63). Patency was achieved
      in 60% (38/63) of men at 1 month after surgery. The mean best sperm count was
      12.8 (0.01-80) x 10(6)/mL, with a 21 (0-30)% motility. Among patients with a
      follow-up of > 1 year, the natural paternity rate was 40%. The median time to
      achieve a natural pregnancy was 14.3 (3-30) months. Pregnancy was achieved with
      in vitro fertilization or intracytoplasmic sperm injection in 31% of cases, all
      using fresh ejaculated sperm. CONCLUSIONS: A favourable patency and pregnancy
      rate can be achieved using microsurgical intussusception vasoepididymostomy. Even
      when assisted-reproductive technology is needed, fresh ejaculated sperm can be
      used without requiring a subsequent sperm retrieval procedure. Thus,
      microsurgical reconstruction of the reproductive tract should be primary
      therapeutic method in cases of azoospermia from epididymal obstruction.

PMID- 16104918
TI  - Extracorporeal shock wave lithotripsy with a transportable electrohydraulic
      lithotripter: experience with >300 patients.
AB  - OBJECTIVE: To review a multicentre experience of using a transportable
      lithotripter (STS-T, Medstone, Inc, Aliso Viejo, CA. USA) for treating patients
      with urolithiasis in all parts of the urinary tract. PATIENTS AND METHODS: In
      all, 326 patients with a total of 370 stones were treated as outpatients with the
      STS-T lithotripter. All patients received a single shock wave lithotripsy
      treatment and were followed after 4-6 weeks in the outpatient clinic, the primary
      endpoint being to determine the efficacy (as defined by the stone-free rate).
      Secondary objectives included establishing a database of patient demographic
      information, stone characteristics, stone location, procedural endpoints, and
      complication rates. RESULTS: In all there were 370 procedures, with a mean of
      2394 shocks administered at an energy level of 24 kV. The mean treatment time was
      51 min, excluding anaesthesia-induction time. The mean stone aggregate size was
      8.2 mm; 62% of the stones were in the kidney while 38% were in various locations
      in the ureter. Of the treated stones, 90% had definite or probable evidence of
      fragmentation. The overall stone-free rate after one treatment with the STS-T was
      52.8%. Of patients with residual fragments, most (61%) had fragments of <4 mm in
      aggregate diameter. The overall complication rate was 3.8%, the most common
      complication being postoperative pain. CONCLUSION: The Medstone STS-T
      lithotripter was an effective device for treating urolithiasis in all parts of
      the urinary tract. This system had a high margin of safety, as shown by the low
      complication rate. With no apparent sacrifice of efficacy compared to first
      generation or fixed (not transportable) second-generation devices, the Medstone
      STS-T represents an important advance in the development of a truly transportable
      lithotripter.

PMID- 16104919
TI  - Partial nephrectomy with perfusion cooling for imperative indications: a 24-year
      experience.
AB  - OBJECTIVE: To report our 24-year experience with open nephron-sparing surgery for
      renal tumours, using cold ischaemia achieved by renal artery perfusion, as
      partial nephrectomy for imperative indications is a surgical challenge. PATIENTS
      AND METHODS: From 1980 to 2004, open partial nephrectomy was performed in 717
      patients; of these, 65 (9.1%) with a solitary kidney, synchronous bilateral
      tumours or renal failure in the opposite kidney (imperative indication) had
      surgery under cold ischaemia, achieved by continuous perfusion of Ringer's
      lactate at 4 degrees C through the renal artery, which was clamped and
      cannulated. The tumour was resected in a bloodless field, with biopsies taken
      from the tumour bed. Focusing on patients with an imperative indication and cold
      perfusion, we report our perfusion technique, and the ischaemia time,
      complication rate and cancer-specific survival rate of these patients. RESULTS:
      The mean (SD, range) operative duration was 132 (103, 91-252) min and ischaemia
      time 49 (37, 31-71) min. The most common complications were postoperative
      haemorrhage in 19%, urinary fistula in 8% and acute renal failure in 6% of
      patients. There were no specific complications related to the perfusion technique
      (renal artery stenosis, renal artery or vein thrombosis). The mean (SD, range)
      long-term follow-up of 95 (71, 4.3-231) months showed increased but constant
      creatinine values (95 micromol/L before, 182 micromol/L after surgery; P < 0.05)
      with no need for long-term dialysis. The tumour-specific survival rate was 94%,
      76% and 76% after 1, 5 and 10 years, respectively. CONCLUSIONS: Partial
      nephrectomy under cold ischaemia remains reserved for selected patients with
      renal tumours with an imperative indication. The technique provides excellent
      intraoperative visibility in an absolutely bloodless field, allows surgery with
      no pressure of time, and makes ex vivo workbench surgery with autotransplantation
      unnecessary. Perfusion cooling allows good tumour-specific long-term results,
      with stable residual kidney function sufficient to prevent dialysis.

PMID- 16104920
TI  - Should the upper tracts be imaged for microscopic haematuria?
AB  - OBJECTIVE: To determine the relative prevalence of various definitions of
      microscopic haematuria (MH) in patients with renal neoplasms and controls, and to
      predict the likely outcome of renal imaging for those definitions. PATIENTS AND
      METHODS: In a retrospective case-control study 278 adult men and woman seen
      between 1998 and 2003 with untreated renal neoplasms were compared to controls
      matched for age and sex. All cases and controls had renal imaging within 6 months
      of a urine analysis. Patients were excluded for gross haematuria or other
      conditions associated with MH but not relevant to upper tract imaging. Adjusted
      odds ratios (OR) computed for 13 definitions of MH by conditional logistic
      regression were the primary outcome measures. Additional outcome measures were
      ORs in selected subsets. Hypothetical performance characteristics of a positive
      urine analysis were then derived to predict the likely results of detecting renal
      neoplasms for each definition of MH. RESULTS: The OR (95% confidence interval)
      for the entire series of cases and controls, both symptomatic and asymptomatic,
      was 2.0 (1.02-3.92, P = 0.04) for MH defined as > or = 4 red blood cells per high
      power field (RBC/HPF) and 2.2 (1.09-4.52, P = 0.03) for > or = 5 RBC/HPF. No
      significant OR was calculated for < or = 3 RBC/HPF, nor for a subgroup of
      patients with MH in a routine urine analysis obtained during a periodic health
      examination. Symptomatic patients had an OR of 13.68 (1.6-117.1, P = 0.02) for MH
      defined as > or = 5 RBC/HPF. The sensitivity of a positive test decreased from
      24.8% to 5.04% as the definition for MH became more stringent. The theoretical
      positive predictive value (assuming a prevalence of renal cell neoplasms of
      0.25%) of the most stringent definition of MH was 0.58%. CONCLUSIONS: Patients
      with renal neoplasms have about twice the prevalence of MH with > or = 4 or 5
      RBC/HPF in a single urine sample compared with matched controls, but this
      difference has little impact on the hypothetical detection rate of renal cancer.
      Imaging the kidney for low-grade MH in a routine urine analysis discovered at a
      periodic health examination in an otherwise asymptomatic patient is tantamount to
      screening without cause, and can be deferred for selected patients. The clinical
      context is as important as the degree of MH when deciding to image the kidneys.

PMID- 16104921
TI  - Donor-site morbidity in buccal mucosa urethroplasty: lower lip or inner cheek?
AB  - OBJECTIVE: To evaluate donor-site complications of buccal mucosa urethroplasty
      and whether there is a difference in morbidity between harvesting the mucosa
      graft from the inner cheek or the lower lip. PATIENTS AND METHODS: Twenty-four
      consecutive patients with recurrent urethral strictures were treated with buccal
      mucosa urethroplasty in our department between September 2002 and April 2004. In
      12 patients the graft was harvested from the lower lip or cheek and lower lip
      (group 1), and in 12 patients from the cheek (group 2). The mean (range) age of
      patients was 51 (26-66) years in group 1 and 53 (32-75) years in group 2. The
      mean (range) graft length was 6.2 (2-16) cm in group 1 and 5.7 (2-13) cm in group
      2. All patients were followed up using a mailed questionnaire that asked about
      pain, numbness, difficulties in mouth opening or ingestion, and satisfaction,
      monthly for the first 3 months and then every 6 months. The mean (range) follow
      up was 12.5 (6-23) months. RESULTS: There were no bleeding complications or
      disturbances in wound healing. All of the patients reported numbness in the area
      of the mental and buccal nerves, and graft-site tenderness after surgery. In
      group 1, the pain lasted for a mean (range) of 5.9 (0.5-22) months, compared to 1
      (0.1-7) months in group 2 (P = 0.022). Perioral numbness lasted for a mean
      (range) of 10.3 (0.5-23) months in group 1 and 0.85 (0.1-3) months (P = 0.0027)
      in group 2. There were no statistically significant differences in problems with
      mouth opening or food intake between the two groups, but the patients in group 1
      seemed to be less satisfied (6/12 patients satisfied) than those in group 2
      (11/12 patients satisfied). CONCLUSIONS: Buccal mucosa graft harvesting from the
      lower lip and the inner cheek are both feasible, but harvesting from the lower
      lip resulted in a significantly greater long-term morbidity, which resulted in a
      lower proportion of satisfied patients. This seems to be due to a long-lasting
      neuropathy of the mental nerve. We therefore have changed our technique entirely
      from lower lip to inner cheek graft harvesting, whenever possible.

PMID- 16104922
TI  - Colour Doppler ultrasonographic location of the bulbourethral artery, and its
      impact on surgical outcome.
AB  - OBJECTIVE: To assess the location of bulbourethral arteries in men with a
      'normal' urethra and to study anatomical alterations in men with urethral
      stricture. PATIENTS AND METHODS: A linear-array transducer was used on the
      ventral surface of the penis to study the urethra. Fifteen men with a normal
      urethra and 15 with a stricture of the bulbar urethra were assessed. After
      conventional grey-scale imaging to evaluate the extent of disease, the urethral
      artery in the bulbar urethra was located by colour Doppler ultrasonography.
      RESULTS: The site of the urethral arteries in 'normal' men varied among
      individuals; they were at the 10-2 o'clock position in six men, 8-10 o'clock and
      2-4 o'clock in six, and at the 4-8 o'clock position in three. In normal men the
      symmetry of arteries was maintained and the mean distance from the lumen was 2.67
      mm. In men with urethral stricture, there was a loss of symmetry in all cases. In
      a dense stricture the urethral arteries could not be detected on either side in
      three of cases, while only a single artery was seen in three. In two men, both
      the arteries were on one side. The mean distance of the urethral artery from the
      lumen of urethra was 1.88 mm. CONCLUSIONS: Contrary to the popular belief that
      the urethral arteries are located at the 3 and 9 o'clock position, we found that
      there was no predictable pattern for their anatomy. These observations might have
      implications for treating urethral stricture disease with visual internal
      urethrotomy, as they could help to avoid injury to the bulbourethral artery.

PMID- 16104923
TI  - Refractory monosymptomatic nocturnal enuresis: a combined stepwise approach in
      childhood and follow-up into adolescence, with attention to the clinical value of
      normalizing bladder capacity.
AB  - OBJECTIVE: To assess the importance of normalizing bladder capacity to the age
      expected capacity in children with refractory monosymptomatic nocturnal enuresis
      (MNE), and to evaluate the long-term results when these children grow into
      adolescence. PATIENTS AND METHODS: The study included 34 children with refractory
      MNE; all were treated > 5 years earlier for their MNE using a combined stepwise
      approach, consisting of retention control training, oxybutynin and an enuresis
      alarm. Data were obtained on their enuretic state, night-time voiding behaviour
      and bladder capacity, from a questionnaire and a voiding chart. RESULTS: Before
      starting treatment, all patients had a bladder capacity that was too small for
      their age. After the combined stepwise approach, MNE improved in all patients and
      24 (71%) were cured. Although the bladder capacity was increased to the age
      expected capacity in 26 (76%), most woke at night to void. Currently, at a mean
      of 7.7 years after the primary treatment, 28 (82%) of the patients are completely
      dry at night, of whom 15 (54%) arouse to void for 35% of the nights. Six patients
      (18%) still have some enuretic episodes. Only those who were dry after primary
      treatment and remained dry had a normal age-expected increase in bladder
      capacity. For all others there was a decrease in age-related bladder capacity.
      CONCLUSIONS: In patients with refractory MNE, a combined stepwise approach
      improves and may even eliminate enuresis, but normal night-time bladder behaviour
      in adolescence and adulthood is only achieved in some. Furthermore, about a fifth
      still have some enuretic episodes.

PMID- 16104924
TI  - Apoptosis and proliferation in human undescended testes.
AB  - OBJECTIVE: To study apoptosis and proliferation in the testes of children with
      undescended testes; the degree to which undescended testes contributes to a
      patient's ultimate fertility is debatable, but undescended testes have fewer germ
      cells, and some have proposed that apoptosis is an important cause. PATIENTS AND
      METHODS: Testis biopsies were taken at the time of orchidopexy in a consecutive
      series of children undergoing surgical repair for undescended testes.
      Immunohistological techniques were used to detect apoptosis and proliferation,
      and the numbers of cells undergoing apoptosis or proliferation per 50
      seminiferous tubules were recorded. RESULTS: Inguinal testes had less apoptosis
      than abdominal testes, with a mean (sd) of 0.71 (1.31) vs 1.63 (1.95) apoptotic
      cells per 50 seminiferous tubules (P < 0.02). Similarly, there was less apoptosis
      in children aged > 1 years than in children aged < 1 years (0.68 (1.40) vs 1.35
      (1.56); P < 0.03). Proliferation was very limited in all cryptorchid testes. In
      contrast to cryptorchid testes, five autopsy controls had many more apoptotic
      cells, (10.60 (1.34) per 50 seminiferous tubules), and many more proliferating
      cells, (8.40 (6.43) per 50 seminiferous tubules). CONCLUSION: In contrast to
      animal studies, neither apoptosis nor proliferation was common in undescended
      testes from 6 months of age onward. However, apoptosis was more common in
      abdominal testes and in children aged < 1 year. It is likely that, if substantial
      apoptosis occurs in human undescended testes, it occurs before 6 months of age.

PMID- 16104925
TI  - Combined low-dose imatinib mesylate and paclitaxel lack synergy in an
      experimental model of extra-osseous hormone-refractory prostate cancer.
AB  - OBJECTIVE: To determine the efficacy of low-dose imatinib mesylate (STI571) alone
      or combined with a taxane (paclitaxel) in inhibiting the growth of experimental
      extra-osseous hormone-refractory prostate cancer. MATERIALS AND METHODS:
      Orthotopic PC3 prostate tumours were established in male severe combined
      immunodeficient mice; on day 3 the mice were randomly assigned to one of four
      groups: paclitaxel 10 mg/kg intraperitoneally once a week; STI571 50 mg/kg once a
      day for 6/7 weekdays; combined paclitaxel and STI571; and vehicle-treated
      controls. On day 40, the primary prostate tumour and metastatic lymphadenopathy
      were removed and measured. Effects were correlated with tumour cell proliferation
      and microvessel density. RESULTS: Paclitaxel reduced the mean tumour weight and
      volume by 21.3% (not significant) and 73.7% (P < 0.05), respectively, compared to
      controls, and reduced the number of lymph node metastases by 49.1% (P < 0.05) and
      mean lymph node size by 13.5% (not significant). Adding low-dose STI571 had a
      small additive effect on tumour weight and the incidence of lymph node
      metastases, but this was not significant compared to paclitaxel alone. STI571
      alone did not inhibit tumour progression. Antitumour effects were associated with
      parallel changes in tumour cell proliferation with no significant changes in neo
      angiogenesis. CONCLUSION: Combined low-dose STI571 and paclitaxel had little
      synergy in this experimental model. Low-dose STI571 monotherapy was not effective
      in extra-osseous disease, apparently due to a site-specific failure to up
      regulate beta-platelet-derived growth factor receptor expression in prostate
      cancer cells and associated tumour stroma.

PMID- 16104926
TI  - A simple procedure for isolating microgram quantities of biologically active
      bikunin from human urine.
AB  - OBJECTIVE: To report a simple, relatively rapid protocol to isolate biologically
      active bikunin from human urine using ion-exchange-trypsin affinity
      chromatography. Bikunin is a protease inhibitor which has been shown to play a
      role in various processes, including inhibition of calcium oxalate
      crystallization, the regulation of proliferation and modulation of
      carcinogenesis. The unavailability of the purified protein has hampered studies
      on bikunin's expanding role in these processes. MATERIALS AND METHODS: Female
      human urine was dialysed (15 kDa threshold) and crudely fractionated with a
      double-saturated ammonium sulphate precipitation. The first precipitation was
      with 35% saturated ammonium sulphate, and the supernatant was harvested, and the
      second with 90% saturated ammonium sulphate, and the precipitate collected. The
      protein mixture was then passed over Sepharose SP-fast-flow cation exchange and
      Sepharose Q-fast-flow anion exchange columns connected in series. The final
      purification was with a trypsin-affinity column which selectively bound bikunin.
      RESULTS: This procedure could recover 1 microg of bikunin per 2 mL of urine, and
      the final product was essentially free of contaminating inter-alpha-trypsin
      inhibitor heavy chains or bikunin-heavy chain conjugates. Product purity was
      confirmed by two-dimensional polyacrylamide gel electrophoresis combined with
      silver staining or Western blot. All isolations contained the 17 kDa minimally
      glycoslyated/sulphated form of bikunin and the 28 kDa form of bikunin. Some
      preparations also contained 33-48 kDa forms of bikunin. The protein cores of all
      three proteins were confirmed to be bikunin by mass spectrometry and Western
      blot. Harvested bikunin retained its trypsin inhibitory activity (L
      benzoylarginine-p-nitroanilide assay). Preparations containing the 33-45 kDa form
      had two to three times more trypsin inhibitory activity than preparations without
      this band. CONCLUSIONS: This novel ion exchange-trypsin affinity chromatography
      protocol uses only two chromatographic steps. The product consists of three
      isomers of biologically active bikunin, free of contaminating heavy chains or
      bikunin-heavy chain conjugates. The ready availability of purified bikunin should
      facilitate future studies of bikunin's emerging role in urolithiasis,
      proliferation and carcinogenesis.

PMID- 16104927
TI  - Intracrystalline proteins and urolithiasis: a comparison of the protein content
      and ultrastructure of urinary calcium oxalate monohydrate and dihydrate crystals.
AB  - OBJECTIVE: To compare the ultrastructure and protein content, particularly
      prothrombin fragment 1 and osteopontin, of calcium oxalate monohydrate (COM) and
      calcium oxalate dihydrate (COD) crystals precipitated from human urine, and their
      susceptibility to proteolysis, to try to clarify the role of intracrystalline
      proteins in urolithiasis, as differences between these types of crystal may
      determine whether calcium oxalate crystals nucleated in urine progress to stone
      formation. MATERIALS AND METHODS: Sodium dodecyl sulphate gel electrophoresis and
      Western blotting were used to analyse demineralized extracts of COM and/or COD
      crystals deposited from the same centrifuged and filtered urine (which contains
      abundant urinary proteins) by adjusting the calcium concentration to 2 and 7
      mmol/L, respectively. Similar analyses were performed on COM and COD crystals
      deposited from ultrafiltered urine (which contains only proteins of < 10 kDa) and
      then incubated in centrifuged and filtered urine, as well as crystals generated
      in the presence of increasing concentrations of proteins derived from the organic
      matrix of urinary calcium oxalate crystals. Field-emission scanning electron
      microscopy was used to assess effects of proteinase K and cathepsin D on internal
      and superficial crystal structure. RESULTS: Osteopontin was undetectable in COM
      extracts, but clearly visible in COD. Prothrombin fragment 1 was abundant in COM,
      but present in COD in lesser amounts than osteopontin. The selectivity was also
      the same with crystals from ultrafiltered urine that were incubated in
      centrifuged and filtered urine: prothrombin fragment 1 binding was favoured by
      low calcium concentration, while osteopontin bound at higher levels. Scanning
      electron microscopy of COM and COD digested with proteinase K and cathepsin D
      revealed superficial and internal texture, as wells as surface erosion, in
      crystals from centrifuged and filtered urine, thus confirming the presence of
      intracrystalline proteins. Such features were absent from crystals precipitated
      from ultrafiltered urine. CONCLUSION: Binding of osteopontin and prothrombin
      fragment 1 to calcium oxalate is dictated primarily by ambient calcium
      concentration. Each protein may inhibit urolithiasis by inhibiting
      crystallization of its preferred crystal habit, and by facilitating the
      intracellular disintegration and dissolution of crystals attached to and
      internalized by renal epithelial cells.

PMID- 16104928
TI  - A tissue-engineered suburethral sling in an animal model of stress urinary
      incontinence.
AB  - OBJECTIVE: To create and evaluate the functional effects of a tissue-engineered
      sling in an animal model of stress urinary incontinence (SUI). MATERIALS AND
      METHODS: Twenty female Sprague-Dawley rats were divided into four equal groups: a
      control group (C) had no intervention before the leak-point pressure (LPP) was
      measured; a denervated group (D) had bilateral proximal sciatic nerve transection
      (PSNT) and periurethral dissection with no sling placed; group S had concomitant
      bilateral PSNT and a suburethral sling of small intestinal submucosa (SIS)
      placed; and group (M) had concomitant bilateral PSNT with implantation of a
      tissue-engineered sling. The suburethral sling was placed via a transabdominal
      approach with the sling sutured to the pubic bone. Tissue-engineered slings were
      prepared with muscle-derived cells obtained via the pre-plate technique and
      subsequently seeded for 2 weeks on a SIS scaffold. Suburethral slings were
      implanted 2 weeks before LPP testing, using the vertical-tilt method. RESULTS:
      Surgically placing a suburethral sling is feasible in the female rat, with few
      complications. LPPs from both sling groups (S and M) were not significantly
      different from untreated controls (C). The S, M and C groups all had
      significantly higher LPPs than group D. Importantly, no rat from either sling
      group (S and M) had signs of urinary retention. CONCLUSIONS: Placing tissue
      engineered slings in an animal model of SUI resulted in LPP values that were not
      significantly different from those in untreated control or SIS (S) groups. These
      data show that incorporating muscle stem cells into SIS slings does not adversely
      alter the advantageous mechanical properties of the SIS sling in a model of SUI,
      and provide the basis for future functional studies of tissue-engineered sling
      materials with long-term retention.

PMID- 16104929
TI  - Alterations in connexin expression in the bladder of patients with urge symptoms.
AB  - OBJECTIVE: To compare the formation of gap junctions between detrusor smooth
      muscle cells in situ and the distribution of connexin (Cx)40, Cx43 and Cx45
      expressions in bladder biopsies from a control group (with bladder tumour) and
      from patients with urge symptoms, as smooth muscle cells of the human detrusor
      muscle communicate via gap junctions and express several connexin subtypes,
      alterations of which may be involved in the causes of lower urinary tract
      symptoms. MATERIALS AND METHODS: Connexin expression is prominent in
      myofibroblast-like cells, supposedly involved in afferent signalling pathways of
      the bladder. Their strategic position directly beneath the urothelium suggests
      they are a link between urothelial ATP signalling during bladder filling and
      afferent Adelta-fibre stimulation for co-ordination of bladder tonus and
      initialization of the micturition reflex. Modification of their coupling
      characteristics may have profound impact on bladder sensation. Bladder tissue
      probes of patients undergoing cystectomy or transurethral tumour resection for
      bladder cancer were used as controls. Tissue samples from patients with severe
      idiopathic urge symptoms were taken for exclusion diagnostics of interstitial
      cystitis (IC) and carcinoma in situ. The formation of functional syncytia between
      detrusor smooth muscle cells were examined in dye-coupling experiments by
      injecting with Lucifer Yellow. The morphology and structure of gap junctions were
      assessed by transmission electron microscopy and immunogold labelling of Cx43 and
      Cx45. The expression of connexin subtypes Cx40, Cx43 and Cx45 was compared by
      indirect immunofluorescence, and confocal laser scanning microscopy used for
      semiquantitative analysis. RESULTS: There was dye coupling between smooth muscle
      cells of the detrusor in situ. Electron microscopy and immunogold labelling
      showed very small gap junctional plaques. These findings were confirmed by
      confocal immunofluorescence. Semiquantitative analyses showed significantly
      higher Cx43 expression in the detrusor muscle, and a tendency to higher Cx45
      expression in the suburothelial layer associated with urge symptoms, whereas Cx40
      expression was unaffected. CONCLUSIONS: Smooth muscle cells of the human detrusor
      muscle are coupled by classical gap junctions, forming limited local functional
      syncytia. Both Cx43 and Cx45 are expressed at low levels in normal detrusor. Up
      regulation of Cx43 in patients with urge incontinence supports the possibility of
      functional changes in the syncytial properties of detrusor smooth muscle cells in
      this condition. In addition, the observed increase of Cx45 in the myofibroblast
      cell layer supports the idea that alterations in sensory signalling are also
      involved. Comparison with previous reports implies that the pathophysiology of
      urgency is distinct from that of the unstable bladder and other forms of
      incontinence.

PMID- 16104930
TI  - One drug fits all.

PMID- 16104931
TI  - How to build an inexpensive laparoscopic webcam-based trainer.

PMID- 16104932
TI  - A simple kidney entrapment technique using a zipped plastic bag during
      retroperitoneoscopic radical nephrectomy.

PMID- 16104933
TI  - Role of computed tomography with no contrast medium enhancement in predicting the
      outcome of extracorporeal shock wave lithotripsy for urinary calculi.

PMID- 16104934
TI  - Role of computed tomography with no contrast medium enhancement in predicting the
      outcome of extracorporeal shock wave lithotripsy for urinary calculi.

PMID- 16104935
TI  - Allopurinol provides long-term protection for experimentally induced testicular
      torsion in a rabbit model.

PMID- 16104936
TI  - Technical considerations when obtaining and interpreting prostatic biopsies from
      men with a suspicion of early prostate cancer.

PMID- 16104937
TI  - A prospective randomized trial comparing transurethral prostatic resection and
      clean intermittent self-catheterization in men with chronic urinary retention.

PMID- 16104940
TI  - Correction of cystocele.

PMID- 16104942
TI  - Role of chronic infection and inflammation in the gastrointestinal tract in the
      etiology and pathogenesis of idiopathic parkinsonism. Part 1: eradication of
      Helicobacter in the cachexia of idiopathic parkinsonism.
AB  - BACKGROUND: Neuronal damage in idiopathic parkinsonism may be in response to
      ubiquitous occult infection. Since peptic ulceration is prodromal, Helicobacter
      is a prime candidate. AIM: To consider the candidature of Helicobacter in
      parkinsonism with cachexia. METHODS: We explore the relationship between being
      underweight and inflammatory products in 124 subjects with idiopathic
      parkinsonism and 195 controls, and present the first case-series evidence of
      efficacy of Helicobacter eradication, in parkinsonism advanced to the stage of
      cachexia. RESULTS: Association of a low body mass index with circulating
      interleukin-6 was specific to parkinsonism (p = .002), unlike that with
      antibodies against Helicobacter vacuolating-toxin and cytotoxicity-associated
      gene product (p < .04). Marked reversibility in both cachexia and disability of
      idiopathic parkinsonism followed Helicobacter heilmannii eradication in one case,
      Helicobacter pylori eradication in another, follow-up being > or = 3.5 years. The
      latter presented with postprandial bloating, and persistent nausea: following
      eradication, radioisotope gastric-emptying returned towards normal, and upper
      abdominal symptoms regressed. Reversibility of their cachexia/disability
      contrasts with the outcome of anti-Helicobacter therapy where eradication
      repeatedly failed (one case), and in non-Helicobacter gastritis (three cases).
      Anti-parkinsonian medication remained constant. Intestinal absorption and barrier
      function were normal in all. CONCLUSION: Categorization, according to presence or
      absence of Helicobacter infection, was a useful therapeutic tool in late
      idiopathic parkinsonism.

PMID- 16104943
TI  - Role of chronic infection and inflammation in the gastrointestinal tract in the
      etiology and pathogenesis of idiopathic parkinsonism. Part 2: response of facets
      of clinical idiopathic parkinsonism to Helicobacter pylori eradication. A
      randomized, double-blind, placebo-controlled efficacy study.
AB  - BACKGROUND: Links between etiology/pathogenesis of neuropsychiatric disease and
      infection are increasingly recognized. AIM: Proof-of-principle that infection
      contributes to idiopathic parkinsonism. METHODS: Randomized, double-blind,
      placebo-controlled efficacy study of proven Helicobacter pylori eradication on
      the time course of facets of parkinsonism. Intervention was 1 week's triple
      eradication therapy/placebos. Routine deblinding at 1 year (those still infected
      received open-active), with follow-up to 5 years post-eradication. Primary
      outcome was mean stride length at free-walking speed, sample size 56 for a
      difference, active vs. placebo, of 3/4 (between-subject standard deviation).
      Recruitment of subjects with idiopathic parkinsonism and H. pylori infection was
      stopped at 31, because of marked deterioration with eradication failure. Interim
      analysis was made in the 20 who had reached deblinding, seven of whom were
      receiving antiparkinsonian medication (long-t(1/2), evenly spaced) which remained
      unchanged. RESULTS: Improvement in stride-length, on active (n = 9) vs. placebo
      (11), exceeded size of effect on which the sample size was calculated when
      analyzed on intention-to-treat basis (p = .02), and on protocol analysis of six
      weekly assessments, including (p = .02) and excluding (p = .05) those on
      antiparkinsonian medication. Active eradication (blind or open) failed in 4/20,
      in whom B-lymphocyte count was lower. Their mean time course was: for stride
      length, -243 (95% CI -427, -60) vs. 45 (-10, 100) mm/year in the remainder (p =
      .001); for the ratio, torque to extend to flex relaxed arm, 349 (146, 718) vs. 58
      (27, 96)%/ year (p < .001); and for independently rated, visual-analog scale of
      stance-walk videos (worst-best per individual identical with 0-100 mm), -64 vs. 
      3 mm from anterior and -50 vs. 11 lateral (p = .004 and .02). CONCLUSIONS:
      Interim analysis points to a direct or surrogate (not necessarily unique) role of
      a particular infection in the pathogenesis of parkinsonism. With eradication
      failure, bolus release of antigen from killed bacteria could aggravate an effect
      of ongoing infection.

PMID- 16104944
TI  - Role of chronic infection and inflammation in the gastrointestinal tract in the
      etiology and pathogenesis of idiopathic parkinsonism. Part 3: predicted
      probability and gradients of severity of idiopathic parkinsonism based on H.
      pylori antibody profile.
AB  - BACKGROUND: Eradicating Helicobacter may convert rapidly progressive idiopathic
      parkinsonism to quieter disease, however only a minority of probands have
      evidence of current infection. AIM: To explore the cross-sectional fit of
      parkinsonism as an extra-alimentary consequence of Helicobacter pylori, using the
      serum antibody profile. METHODS: A discriminant index for parkinsonism was based
      on the Western Blot pattern of IgG antibodies against electrophoretically
      separated H. pylori antigens in 124 subjects with idiopathic parkinsonism, 196
      without. In parkinsonism, association was assessed between index and 1,
      anthropometric measures; 2, current and 3, increase over 4 years in hypokinetic
      and psychomotor/psychometric disability; and 4, a global score of current
      severity. RESULTS: Predicted probability of being labeled parkinsonian was
      greatest with cytotoxin-associated-gene-product (CagA) positivity and vacuolating
      toxin negativity (p = .03 and .004, respectively, for antibody-age interactions),
      and urease-B negativity (p = .03, irrespective of age). In this circumstance, the
      odds for parkinsonism increased fivefold by age 80 years (p = .001). Helicobacter
      status, according to anti-urease enzyme-linked immunosorbent assay (ELISA), did
      not complement the model. Gradients, of clinically relevant size, were found
      between index and disease burden, despite the potentially confounding effect of
      antiparkinsonian medication. The higher the index 1, the worse was posture, as
      gauged by forward displacement of occiput (p = .04), 2, the shorter mean stride
      length (p = .003), longer reaction time (= .002) and lesser cognitive efficiency
      (= .03), 3, the greater their deterioration (p = .006, .002, and .03
      respectively), and 4, the greater the overall severity of parkinsonism (< .001).
      CONCLUSION: The apparent importance of H. pylori in the etiology/pathogenesis of
      idiopathic parkinsonism is not confined to those with evidence of current
      infection.

PMID- 16104945
TI  - Cellular mucosal defense during Helicobacter pylori infection: a review of the
      role of glutathione and the oxidative pentose pathway.
AB  - Helicobacter pylori is the primary cause of gastritis and peptic ulcer disease
      and is known to infect greater than 50% of the world's population. It is also
      known to lead to the onset of gastric cancer and unless treated, lasts throughout
      life in most individuals. Mouse models of H. pylori infection have improved our
      ability to study this organism and can be used to investigate the host mucosal
      response to the infection, particularly the early events postinoculation.
      Previous studies have shown that H. pylori infection leads to an increased
      production of reactive oxygen species within the gastric mucosa which are thought
      to play a major role in the mediation of associated disease. Recent studies have
      shown differences in the availability of an important antioxidant, glutathione,
      during chronic H. pylori infection. The availability of glutathione is primarily
      controlled by the activity of the oxidative pentose pathway. This review proposes
      that the severity of inflammation and damage associated with H. pylori infection
      is dependent on the ability of mucosal cells to counteract the increased load of
      reactive oxygen species. It is hypothesized that the oxidative pentose pathway
      and glutathione availability are important factors modulating this response. It
      is suggested that the therapeutic regulation of glutathione availability could
      provide a novel method for preventing or reducing the damage caused during H.
      pylori infection.

PMID- 16104946
TI  - Helicobacter pylori infection in dental professionals: a 6-year prospective
      study.
AB  - BACKGROUND: In a previous cross-sectional study, we reported no significant
      differences between dentists and controls in the seroprevalence of Helicobacter
      pylori. The aim of the present study is to determine the risk and the risk
      factors for new infection of H. pylori. This is the first report designed to
      assess the seroprevalence of H. pylori infection over a 6-year period in a cohort
      of dental professionals. MATERIALS AND METHODS: We collected blood samples from
      employees of Kanagawa Dental College to test for serum anti-H. pylori IgG. We
      collected 566 samples in 1997 and another 551 samples in 2003. Questionnaires
      completed by participants provided information about risk factors of H. pylori
      infection. RESULTS: A total of 236 employees were tested on both occasions. Of
      the 170 who were seronegative in 1997, we randomly selected 59 from among the
      dental professionals (dentists and dental nurses). As controls, we selected 59
      from among the nonclinical staff who were matched for sex and age. The risk of
      new infection of H. pylori for dental professionals is 1.12%/year and the
      relative risk is 4.0. We determined the risk factors for acquiring H. pylori
      using logistic regression. Adjusted odds ratio being a dental professionals was
      2.68 (95% confidence interval [CI]: 0.55-19.67), having upper gastrointestinal
      family history was 4.84 (95% CI: 0.83-26.72), and age over 40 was 8.83 (95% CI:
      1.36-177.24). CONCLUSION: This 6-year prospective study shows that dental
      professionals are at greater risk of being infected by H. pylori than are
      controls.

PMID- 16104947
TI  - Helicobacter pylori associated with glossitis and halitosis.
AB  - BACKGROUND: Helicobacter pylori is a curved microaerophilic Gram-negative
      bacterium considered as a risk factor for gastric cancer. The aim of this study
      was to find an association between burning sensations, acid taste, halitosis, and
      lingual hyperplasia with the effect of H. pylori on the mouth. MATERIALS AND
      METHODS: A total of 124 subjects with different gastric diseases were studied: 46
      patients with burning, halitosis and lingual dorsum hyperplasia and 78 patients
      with other diseases. RESULTS: The detection of H. pylori in the oral cavity by
      histopathologic diagnosis and molecular biology was confirmed in 40/46 (87%)
      patients with burning, halitosis, and lingual hyperplasia, and in 2/78 (2.6%)
      subjects with other diseases. Chi2: 91.26 (p < .001) Mantel-Haenszel. CONCLUSION:
      This trial showed an association between H. pylori and burning, halitosis, and
      lingual hyperplasia, and further considered this bacterium a risk factor for
      gastric infection.

PMID- 16104948
TI  - Detection of Helicobacter pylori-specific genes in the oral yeast.
AB  - BACKGROUND: Until today, human stomach is the only recognized habitat of
      Helicobacter pylori. However, recruitment of DNA-based methods has made possible
      the detection of H. pylori in water and oral cavity, thus suggesting fecal-oral
      and oral-oral routes for transmission of H. pylori, respectively. In this study,
      yeast has been proposed as a common vector for transmission of H. pylori. Thus
      designed primers were recruited to target 16S rDNA and cagA genes in the oral
      yeasts by PCR. MATERIALS AND METHODS: Eighteen yeasts were examined
      microscopically for the presence of bacterial-like bodies. DNAs were extracted
      from oral yeasts using phenol-chloroform method. Amplification conditions were
      optimized as 33 cycles and annealing temperatures of 63 degrees C for 16S rDNA
      and 51 degrees C and 52 degrees C for cagA gene which was targeted in two steps.
      DNAs of H. pylori and Saccharomyces cerevisiae were used as controls. Polymerase
      chain reaction (PCR) products of two genes from one yeast and from H. pylori were
      cloned in pCAP and subsequently subcloned in pSK+ and were sequenced. RESULTS:
      Bacterial-like bodies were observed in all oral yeasts. The amplified products of
      16S rDNA from all oral yeasts were homologous in size with those of H. pylori.
      Fifteen out of eighteen (83%) yeasts contained cagA gene, homologous to H.
      pylori. CagA was not amplified from three yeasts and S. cerevisiae. Analysis of
      the sequenced products of 16S rDNA and cagA from one oral yeast showed 98%
      homology with those of H. pylori. CONCLUSIONS: The presence of H. pylori inside
      the yeast was indicated by light microscopy and PCR. It appears that yeasts,
      which are abundant in nature and thrive the mucosal surfaces of human, might
      serve as reservoirs and vehicles of H. pylori.

PMID- 16104949
TI  - Vacuolating cytotoxin A is associated with increased thrombin generation in
      gastric mucosa.
AB  - BACKGROUND: Activation of the coagulation system is a critical response for both
      the repair of tissue injury and the host defense against microbial pathogens.
      Activation of the coagulation cascade culminates with the generation of thrombin.
      In vitro studies have shown that thrombin protects gastric epithelial cells from
      injury. The present study was undertaken to assess in vivo the relationship
      between gastric intramucosal generation of thrombin and Helicobacter pylori
      infection. MATERIALS AND METHODS: This study comprised 59 patients with
      gastroduodenal disorders. There were 27 patients with H. pylori infection (Hp+),
      14 without it (Hp-), and 18 patients with cured H. pylori infection (Hp c). The
      gastric intramucosal concentrations of thrombin-antithrombin complex (TAT),
      epidermal growth factor (EGF), prostaglandin E2 (PGE2), and vacuolating cytotoxin
      A (VacA) were measured by specific immunoassays. RESULTS: The level of TAT was
      significantly increased in patients with Hp+ compared to Hp- and Hp c. The levels
      of TAT, EGF and PGE2 were higher in VacA (+) patients than in those with VacA (
      ). VacA induced significant expression of tissue factor in gastric epithelial
      cells in vitro. The gastric intramucosal level of VacA antigen was proportionally
      and significantly correlated with TAT, EGF and PGE2 in Hp+ patients. The level of
      TAT was proportionally and significantly correlated with EGF in Hp+ patients but
      not in Hp- and HP c patients. CONCLUSIONS: These results showed that VacA
      produced by H. pylori is associated with increased thrombin generation, and that
      thrombin may play a protective role in H. pylori-associated gastroduodenal
      disorders.

PMID- 16104950
TI  - Experimental Helicobacter pylori infection induces antral-predominant, chronic
      active gastritis in hispid cotton rats (Sigmodon hispidus).
AB  - BACKGROUND: The hispid cotton rat has proven to be an excellent animal model for
      a variety of human infectious disease agents. This study was performed to
      evaluate the use of the cotton rat as a model of Helicobacter pylori infection.
      MATERIALS AND METHODS: Thirty-eight inbred cotton rats were orogastrically
      inoculated with a human strain of H. pylori. Twenty-eight control cotton rats
      were dosed with vehicle only. Animals were sacrificed at 2, 4, 12, 26, or 38
      weeks after inoculation for bacterial and histologic and immunologic
      examinations. RESULTS: Helicobacter pylori was cultured from the glandular
      stomach of 89% of the infected cotton rats. The level of colonization was
      consistently high (approximately 10(4-6) colony-forming units/g tissue).
      Histologically, the spiral bacteria were demonstrated on the epithelial surface
      and in the foveolae of the gastric mucosa with highest numbers in the antrum. H.
      pylori infection was associated with antral-predominant, chronic active gastritis
      which progressively increased in severity over time. By week 26 of infection,
      moderate antral gastritis had developed with frequent involvement of the
      submucosa and formation of lymphocytic aggregates. Splenic T cells from infected
      cotton rats expressed mRNAs for interferon-gamma, interleukin-4, interleukin-6,
      and interleukin-10 following in vitro stimulation with H. pylori. Serum levels of
      H. pylori-specific immunoglobulin G were significantly elevated after 12 weeks of
      infection. CONCLUSIONS: The H. pylori-infected cotton rat represents a novel
      animal model that should prove useful for studies of H. pylori-induced chronic
      active gastritis and factors affecting gastric colonization by this pathogen.

PMID- 16104951
TI  - Oral vaccination against Helicobacter pylori with recombinant cholera toxin B
      subunit.
AB  - BACKGROUND: The innocuous pure recombinant cholera toxin B-subunit (rCTB) is very
      attractive as a strong adjuvant for host immunization, but little is known about
      rCTB's gastric mucosal immunoadjuvanticity against Helicobacter pylori. The
      immunoadjuvanticity of rCTB against H. pylori was tested. MATERIAL AND METHODS:
      Mice were immunized with sonicated H. pylori and rCTB orally or intranasally and
      sacrificed on day 42 after immunization. Passive cutaneous anaphylaxis (PCA) test
      was performed to evaluate IgE-mediated anaphylaxis with serum from mice to which
      H. pylori-antigen with rCTB had been administered. Immunoglobulin titer specific
      to H. pylori in serum, lavation of the gastrointestinal tracts and feces were
      examined. Gastritis in vaccinated mice after a challenge was assessed with the
      scoring defined from grading of gastric inflammation. H. pylori proliferation
      after immunization was investigated by counting colony forming units (CFU) per
      gram of stomach tissue. RESULTS: PCA test exhibited no reactions against the
      serum from mice immunized with H. pylori-antigen with rCTB administered orally
      and intranasally. Oral and nasal coadministrations of rCTB significantly raised
      systemic and mucosal immunities against H. pylori and suppressed proliferation of
      H. pylori in gastric mucosa. The score of gastritis in mice immunized orally was
      significantly higher than that of mice immunized nasally due to postimmunization
      gastritis. Only oral administration of rCTB suppressed H. pylori proliferation as
      compared with intranasal administration and without rCTB. CONCLUSIONS: The
      present study indicated that rCTB has systemic and mucosal immunoadjuvanticities
      against H. pylori and that oral vaccination with rCTB might additively support
      antibiotic eradication.

PMID- 16104952
TI  - Detection of Helicobacter pylori DNA by a simple stool PCR method in adult
      dyspeptic patients.
AB  - INTRODUCTION: Helicobacter pylori is the major agent causing peptic ulcer,
      gastric cancer and mucosa-associated lymphoid tissue (MALT) gastric lymphoma. A
      simple stool polymerase chain reaction (PCR) method was performed and compared
      with the gold standards for the diagnosis of H. pylori infection. MATERIAL AND
      METHODS: A total of 54 adult patients (mean age, 46.41 +/- 13.12 years) with
      dyspeptic symptoms from Gastroenterology at Dokuz Eylul University Hospital
      between May and November 2003 were included. Two antrum and corpus biopsies were
      taken from each patient. Infection by H. pylori was defined as positivity and
      negativity of the gold standards. DNA extraction of stool specimens was done
      using QIAamp DNA Stool Mini Kit (QIAGEN) and PCR conditions included
      amplification and reamplification steps using the H. pylori ureA gene specific
      primers (HPU1, HPU2) and were visualized on 1% agarose gel stained with ethidium
      bromide. RESULTS: Forty-six of 54 patients (85.2%) were diagnosed positive and
      eight (14.8%) were negative for H. pylori infection by the gold standard methods.
      Thirty-two patients were positive (59.3%) and 22 of them (40.7%) were detected
      negative by stool PCR method. The stool PCR method and gold standard methods
      showed a statistical difference for the detection of H. pylori infection (p <
      .0001). Sensitivity, specificity, likelihood ratio, and positive and negative
      predictive values were 65.22%, 75%, 2.61%, 93.75%, and 27.7%, respectively.
      DISCUSSION: The PCR on the stool specimens resulted as being a very specific
      test. We suggest that a simple stool PCR method that we developed can be used to
      detect H. pylori, virulence genes, and in drug resistance studies either first
      line diagnostic methods in the laboratory or in the clinical management of
      dyspeptic patients.

PMID- 16104953
TI  - Alarming clarithromycin resistance of Helicobacter pylori in Turkish population.

PMID- 16104954
TI  - Bone reactions to longstanding functional load at implants: an experimental study
      in dogs.
AB  - OBJECTIVES: The aims of the present investigation were (i) to study marginal bone
      level alterations following implant installation, abutment connection and
      functional loading and (ii) to analyse bone tissue reactions to functional load.
      MATERIAL AND METHODS: Six beagle dogs, about 1-year old, were used. All
      mandibular pre-molars were extracted. Three months later four implants of the
      Astra Tech Implants Dental System were installed in one side of the mandible and
      four standard fixtures of the Branemark System were placed in the contralateral
      side of the mandible. Abutment connection was performed 3 months later and a
      plaque control programme was initiated. Three months after abutment connection
      fixed partial dentures (FPDs) made in gold were cemented to the maxillary canines
      and pre-molars. FPDs were also connected to the three posterior implants in each
      side of the mandible, while the mesial implant in each side was used as an
      unloaded control. Radiographs were obtained from all implant sites following
      implant installation, abutment connection and FPD placement. Ten months after the
      FPD placement the radiographic examination was repeated. The animals were
      sacrificed and biopsies from all implant sites were obtained and prepared for
      histological analysis. RESULTS: The radiographic analysis revealed that largest
      amount of bone loss occurred following implant installation and abutment
      connection and that this loss was more pronounced at Branemark than at Astra
      implants. The bone level alterations that were observed at implants exposed to 10
      months of functional load in both implant systems were small and did not differ
      from control sites. The histological analysis revealed that implants exposed to
      functional load exhibited a higher degree of bone-to-implant contact than control
      implants in both implant systems. CONCLUSION: It is suggested that functional
      load at implants may enhance osseointegration and does not result in marginal
      bone loss.

PMID- 16104955
TI  - The effect of immunization on the response to P. gingivalis infection in mice is
      adjuvant-dependent.
AB  - AIM: Studies on vaccines against the periodontal pathogen Porphyromonas
      gingivalis have produced conflicting results, but no consideration has been given
      to the role of different adjuvants in these vaccines. We have previously shown
      that an intra-chamber challenge with heat-killed P. gingivalis was modified by
      immunization with different adjuvants. This study tested the hypothesis that
      different adjuvants in P. gingivalis vaccines would differentially modify the
      host response to a live P. gingivalis infection. RESULTS: Using P. gingivalis
      infected subcutaneous chambers in mice, we show that vaccination with P.
      gingivalis in alum attenuated the pro-inflammatory cytokine levels at the site of
      infection, while the vaccine containing incomplete Freund's adjuvant did the
      opposite. Although both vaccines induced a similar humoral IgG response, P.
      gingivalis-induced abscesses were significantly smaller in the alum-adjuvant
      group. CONCLUSIONS: The results suggest that the immune response and the
      resultant protection to a P. gingivalis infection, in P. gingivalis-vaccinated
      mice, are adjuvant-dependent.

PMID- 16104956
TI  - Is there an association between periodontal disease, prematurity and low birth
      weight? A population-based study.
AB  - BACKGROUND: The relationship between periodontal diseases in pregnancy and
      children born prematurely or with low birth weight has been increasingly
      investigated, showing inconclusive results. OBJECTIVES: To test the link between
      periodontal disease in pregnant women and low birth weight or prematurity.
      METHODS: A population-based, cross-sectional study was carried out in Southern
      Brazil. The sample consisted of 449 parturients who were interviewed and examined
      up to 48 h post-partum. Three outcomes were investigated: low birth weight,
      prematurity and prematurity and/or birth weight. Periodontal disease, the
      exposure, was defined as (i) at least one site with a periodontal pocket; (ii)
      the presence of pockets at four or more sites. Socio-demographic information
      relating to health and maternal habits was collected through a questionnaire and
      by hospital medical records. Simple and multiple regression analysis was
      performed. FINDINGS: There was no statistically significant association between
      periodontal disease and low birth weight. Periodontal pocket was not associated
      with low birth weight and/or pre-term birth after being adjusted. A periodontal
      pocket in at least one site was associated with prematurity (odds ratio=2.6; 95%
      confidence interval 1.0-6.9) even after adjusting for maternal schooling, parity,
      number of previous children of low birth weight, number of pre-natal
      consultations and body mass index. After the introduction of variables relating
      to maternal health during pregnancy, this association disappeared. CONCLUSIONS:
      No association was found between periodontal disease in the mother and the low
      birth weight. An association between prematurity and periodontal pockets was
      found but it was confounded by maternal health variables.

PMID- 16104957
TI  - Evaluation of dentin abrasion during professional tooth cleaning in an in vitro
      model.
AB  - OBJECTIVES: Professional tooth cleaning (PTC) may lead to loss of exposed dentin.
      The aim of the present study was to determine the absolute loss of dentin during
      PTC using various product combinations with an in vitro model. MATERIAL AND
      METHODS: Dentin specimens (72) were randomly assigned to nine groups. In four
      groups each, prophy brushes and prophy cups were used in combination with four
      different abrasives (calcium pyrophosphate, pumice, Hawe cleanic, Nupro coarse).
      In the ninth group, a rubber cup with embedded fluoride and abrasives was used
      (pasteless prophy cup). The treatment time was 37 s. Surface loss was determined
      by profilometry. RESULTS: The surface loss in the nine groups was as following:
      (1) brush/calcium pyrophosphate: 6.18 microm (a); (2) brush/pumice: 5.51 microm;
      (3) brush/Nupro coarse: 10.10 microm (b); (4) brush/Hawe cleanic: 1.88 (a, b);
      (5) prophy cup/calcium pyrophosphate 2.07 (c); (6) prophy cup/pumice: 6.07
      microm; (7) prophy cup/Nupro coarse: 5.93 microm (c); (8) prophy cup/Hawe
      cleanic: 4.93 microm (c); (9) pasteless prophy cup: 11.86 microm (c). Groups with
      the same letter in parentheses are statistically significant different at p<0.05.
      In a pooled analysis, no statistically significant difference between brushes and
      prophy cups was found. CONCLUSION: In the present study, the surface loss of
      about eight PTC procedures was simulated. Hence, the dentin loss ranged between
      0.24 and 1.48 microm per PTC. Therefore, PTC does not seem to be a main factor in
      dentin loss.

PMID- 16104958
TI  - Prognostic factors for alveolar regeneration: effect of space provision.
AB  - OBJECTIVES: The role of space provision as an independent prognostic factor for
      periodontal regeneration remains to be established. The objective of this study
      was to evaluate the role of space provision on alveolar bone regeneration in
      periodontal sites. METHODS: Critical size, supra-alveolar, periodontal defects
      were created in 11 young adult Beagle dogs. Six animals received a porous ePTFE
      device to provide for space provision. Five animals received sham surgery. The
      animals were euthanized at 8 weeks post-surgery. A histometric analysis assessed
      vertical regeneration of alveolar bone and the width of the alveolar crest at the
      base of the defect. Because of the correlation of within-dog measurements, a
      mixed model anova/ancova was used to analyse the data. RESULTS: A significant
      relationship between the width of the alveolar crest at the base of the defect
      and bone regeneration was observed with no significant difference between sites
      receiving the different treatments (p=0.84). Bone regeneration at sites treated
      with the space-providing device was significantly greater compared with that at
      sites treated with sham surgery (p=0.0003), and the difference remained
      significant after adjusting for bone width (p=0.0001). CONCLUSIONS: Space
      provision has a significant effect on alveolar bone regeneration in periodontal
      sites. The width of the alveolar bone appears to influence space provision
      effectively supporting bone regeneration.

PMID- 16104959
TI  - Interleukin-6 gene polymorphism in renal transplant patients with and without
      gingival overgrowth.
AB  - OBJECTIVE: To determine whether there is an association between genotypes of
      interleukin-6 (IL-6) and gingival overgrowth in kidney transplant patients.
      METHODS: Sixty-three unrelated kidney transplant patients suffering from gingival
      overgrowth as well 125 control transplant patients without overgrowth were
      enrolled into the study. Gingival overgrowth was assessed by two independent
      periodontal specialists at 6 months after transplantation. During the post
      transplant period, all patients were given medication, which included cyclosporin
      A, diltiazem or verapamil, prednisone, and azathioprine. IL-6 polymorphism was
      determined using the polymerase chain reaction-restriction fragment length
      polymorphism assay. RESULTS: In kidney transplant patients suffering from
      gingival overgrowth mean score of gingival overgrowth was 1.41+/-0.64, whereas in
      control subjects it was 0.0. Patients with gingival overgrowth induced by
      immunosuppressive medication were characterized by genotypes similar to the
      controls distribution of IL-6. There were no significant differences of analyzed
      genotypes' distribution, i.e. -174G/G, -174G/C and -174C/C between patients with
      gingival overgrowth 33.3%, 39.7%, 27.0% and without gingival overgrowth 30.4%,
      49.6% and 20.0%, respectively. The risk of gingival overgrowth was the highest
      among patients carrying -174C/C genotype (OR 1.48), but did not differ markedly
      from the other genotypes, i.e. -174G/G (OR 1.15) and -74G/C (OR 0.67). Similar to
      genotypes, the distribution of alleles was similar in patients with gingival
      overgrowth and healthy gingiva. The -174G allele was found in 53.2% and 46.8% of
      subjects whereas -174C allele was revealed in 46.8% and 44.8% of patients with
      and without gingival overgrowth, respectively. The evaluated risk of gingival
      overgrowth in patients with -174G allele was 1.09 versus those with healthy
      gingiva. The medication regimen administered in both groups of the study was
      comparable. CONCLUSION: No association between the IL-6 gene polymorphism and
      gingival overgrowth was revealed in kidney transplant patients administered
      cyclosporin A as a principal immunosuppressive agent.

PMID- 16104960
TI  - Radiographic study of the prevalence of periodontal bone loss in Australian
      school-aged children attending the Royal Dental Hospital of Melbourne.
AB  - OBJECTIVES: To investigate the prevalence of alveolar bone loss around the first
      permanent molars, and first and second deciduous molars in Australian school-aged
      children attending the Royal Dental Hospital of Melbourne. METHOD: Nine hundred
      and ninety-five records were examined for useable bitewing radiographs. From
      these, radiographs of 542 Australian school children aged 5-12 years were used.
      The cervical-enamel junction (CEJ) to the alveolar bone crest (ABC) distance was
      measured using the transparent ruler on the magnifier. Each inter-dental site
      that was readable was scored as one for the following categories: not available
      (NA); no bone loss (NBL)- the CEJ-ABC was < or =2 mm; questionable bone loss
      (QBL): the distance from the CEJ-ABC was >2 and <3 mm; and definite bone loss
      (DBL): the distance from the CEJ to ABC was > or =3 mm. RESULTS: Seventy-one
      children (13.0%) were found to have 83 DBL sites, as determined by bone levels
      >3.0 mm from the CEJ. Seventy children had QBL lesions only, 50 children had DBL
      only and 21 children had both. The overall prevalence of bone loss was 26%.
      Second deciduous molars were found to be the most affected teeth with almost 75%
      lesions being distal. These teeth comprised 50% of the DBL lesions. Children of
      Asian-Far Eastern origin had a higher percentage of sites with bone loss compared
      with children of Caucasian origin, being 29.5% and 19.7%, respectively, but lower
      than that of children of Middle-Eastern origin (35.2%). When the data were
      analysed with relation to age, there was no relationship between age and
      prevalence of bone loss. CONCLUSION: In the population studied, there was an
      overall prevalence of periodontal bone loss of 26% and DBL of 13% in an
      Australian school-aged group. Calculus was detected infrequently and, where
      present, was associated with bone loss.

PMID- 16104961
TI  - Analysis of rat calvaria defects implanted with a platelet-rich plasma
      preparation: histologic and histometric observations.
AB  - OBJECTIVES: It has been suggested that degranulating platelet alpha-granules
      release growth factors having a potential to modulate bone formation. The
      objective of this study was to evaluate the osteoconductive potential of a
      platelet-rich plasma (PRP) preparation. METHODS: Thirty adult male Sprague-Dawley
      rats were used. The PRP preparation was obtained from 10 ml of whole blood drawn
      from one age-matched donor rat. The preparation was processed by gradient density
      centrifugation and stored at -80 degrees C until use. Using aseptic techniques,
      the PRP preparation soak loaded onto an absorbable collagen sponge (ACS) or ACS
      alone was surgically implanted into contralateral critical size 6-mm calvaria
      osteotomies in 18 animals. Twelve animals received ACS versus sham surgery in
      contralateral defects. Animals were sacrificed at 4 and 8 weeks when biopsies
      were collected for histologic and histometric analysis. RESULTS: The animals were
      maintained without adverse events. Bone formation was highly variable in sites
      receiving PRP and control treatments. Defect bone fill at 4 weeks averaged (+/
      SD) 28.8+/-27.4% (PRP/ACS) versus 39.1+/-24.4% (ACS; p=0.2626) and 62.0+/-20.0%
      (ACS) versus 71.6+/-32.2% (sham surgery; p=0.1088), and at 8 weeks 81.0+/-12.9%
      (PRP/ACS) versus 64.5+/-28.1% (ACS; p=0.2626) and 75.6+/-34.1% (ACS) versus
      74.1+/-24.2% (sham surgery; p=0.7353). Remnants of the ACS biomaterial were
      observed at both 4 and 8 weeks in sites implanted with PRP/ACS or ACS.
      CONCLUSIONS: The results suggest that the PRP preparation has a limited potential
      to promote local bone formation.

PMID- 16104962
TI  - Impact of smoking on the clinical, microbiological and immunological parameters
      of adult patients with periodontitis.
AB  - OBJECTIVES: The aim of the current study was to assess the impact of smoking on
      the clinical indices, the humoral immune response and the detection frequency of
      putative periodontal pathogens in patients with periodontitis cross-sectionally
      and following therapy. MATERIAL AND METHODS: Clinical measurements, subgingival
      plaque samples, gingival crevicular fluid (GCF) and sera were collected from 40
      untreated patients with moderate-to-advanced chronic periodontitis before and
      after treatment over a period of 6 months. The treatment consisted of the initial
      therapy of scaling and root planing. Smoking status was self-reported and was
      confirmed by cotinine enzyme inhibition assay (CEIA). Whole-mouth clinical
      measurements were recorded with a manual periodontal probe at baseline (BAS) and
      at 6 months (RAS). Selected-site analyses were performed on the deepest site in
      each quadrant before and after therapy and clinical indices were recorded with an
      electronic pressure-sensitive probe. GCF sample volume was quantified using the
      Periotron 6000. Polymerase chain reaction (PCR) was utilized to determine the
      presence of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans,
      Prevotella intermedia, Treponema denticola and Tanerella forsythensis in
      subgingival plaque. Enzyme-linked immunosorbent assay examined the systemic
      antibody titres to these bacteria, and thiocyanate disassociation determined the
      antibody avidity to these organisms. RESULTS: At baseline, smokers showed
      significantly less gingival inflammation and lower GCF volume compared with non
      smokers. After treatment, a compromised clinical outcome was noted for smokers in
      terms of pocket depth reduction and gain in attachment levels. No significant
      differences in the detection of putative periodontal pathogens in subgingival
      plaque existed between smokers and non-smokers. A consistent trend was noted in
      that smokers had lower sera immunoglobulin G antibody titres to these organisms
      before and after treatment (statistically significant for A.
      actinomycetemcomitans). This pattern was less clear when antibody avidities were
      considered, revealing only small differences, if any, between the two groups of
      patients. CONCLUSION: Current data indicate that smokers with periodontal disease
      have a suppressed inflammatory response, a significantly less favourable clinical
      outcome and seem to have an altered host antibody response to antigenic challenge
      than non-smokers. In contrast, the subgingival microflora of smokers appears
      similar to that of non-smokers.

PMID- 16104963
TI  - The natural history of periodontal disease in humans: risk factors for tooth loss
      in caries-free subjects receiving no oral health care.
AB  - AIM: No long-term studies have reported on risk factors for tooth loss in
      subjects without home or professional dental care. The purpose of this report is
      to identify potential risk factors for tooth loss among male Sri Lankan tea
      labourers who participated in a 20-year investigation of the natural history of
      periodontal disease. MATERIAL AND METHODS: Data for this report were obtained
      from the 455 subjects who participated in multiple examinations over the 20-year
      period from 1970 to 1990. Analyses included data from interim examinations in
      1971, 1973, 1977, 1982 and 1985. Oral health assessments included the following:
      (1) attachment levels in millimetres on all mesial and mesio-buccal surfaces,
      excluding third molars; (2) plaque index; (3) gingival index; (4) calculus index;
      (5) caries index; and (6) missing teeth. Other variables included age, history of
      smoking and betel nut use. Statistical analyses included descriptive statistics
      and multivariate repeated-measures modelling with generalized estimating
      equations. RESULTS: Tooth loss was significantly dependent upon interactions
      between the mean attachment loss and betel nut use (Z=3.40; p=0.0007) and history
      of missing teeth (Z=-3.70; p=0.0002). The effect of attachment loss on tooth loss
      was increased in the presence of betel nut and diminished when teeth were already
      missing at baseline. CONCLUSION: History of missing teeth, betel nut use and
      increasing attachment loss were significant predictors of tooth loss over time.
      Betel nut use increased the effect of attachment loss on loss of teeth, while
      history of missing teeth diminished the effect of attachment loss on tooth loss.

PMID- 16104964
TI  - Autogenous bone chips: influence of a new piezoelectric device (Piezosurgery) on
      chip morphology, cell viability and differentiation.
AB  - AIM: The aim of the present study was to investigate the influence of a new
      piezoelectric device, designed for harvesting autogenous bone chips from intra
      oral sites, on chip morphology, cell viability and differentiation. METHODS: A
      total of 69 samples of cortical bone chips were randomly gained by either (1) a
      piezoelectric device (PS), or (2) conventional rotating drills (RD). Shape and
      size of the bone chips were compared by means of morphometrical analysis.
      Outgrowing osteoblasts were identified by means of alkaline phosphatase activity
      (AP), immunhistochemical staining for osteocalcin (OC) synthesis and reverse
      transcriptase-polymerase chain reaction phenotyping. RESULTS: In 88.9% of the RD
      and 87.9% of the PS specimens, an outgrowth of adherent cells nearby the bone
      chips was observed after 6-19 days. Confluence of cells was reached after 4
      weeks. Positive staining for AP and OC identified the cells as osteoblasts. The
      morphometrical analysis revealed a statistically significant more voluminous size
      of the particles collected with PS than RD. CONCLUSION: Within the limits of the
      present study, it may be concluded that both the harvesting methods are not
      different from each other concerning their detrimental effect on viability and
      differentiation of cells growing out of autogenous bone chips derived from intra
      oral cortical sites.

PMID- 16104965
TI  - Tobacco smoking and periodontal bone height in a Saudi Arabian population.
AB  - AIM: To study the association between tobacco smoking, in particular water pipe
      smoking, and periodontal bone height. METHODS: A study sample of 355 individuals
      in the age range 17-60 years was recruited from Jeddah, Saudi Arabia. The smoking
      behavior was registered through a questionnaire during interview. Participants
      were stratified into water pipe smokers (33%), cigarette smokers (20%), mixed
      smokers (19%) and non-smokers (28%). The periodontal bone height was measured
      from digital panoramic radiographs mesially and distally to each tooth and
      expressed as a percentage of the root length. RESULTS: The mean periodontal bone
      height was 76.2% for water pipe smokers, 75.8% for cigarette smokers, 80.2% for
      mixed smokers and 80.9% for non-smokers. The association between smoking and mean
      bone height was statistically significant controlling for age (p<0.001). The
      association between life-time smoking exposure and mean bone height controlling
      for age was statistically significant in water pipe smokers and cigarette smokers
      (p<0.01). The prevalence of bone loss in excess of 30% of the bone height was 27%
      in water pipe smokers, 24% in cigarette smokers, 9% in mixed smokers and 6% in
      non-smokers. The prevalence was significantly greater in water pipe smokers and
      cigarette smokers compared with non-smokers (p<0.001). The relative risk of
      periodontal bone loss associated with water pipe and cigarette smoking after
      adjustment for age was 3.5-fold and 4.3-fold elevated, respectively, compared
      with non-smoking (p<0.01). CONCLUSION: An association between tobacco smoking and
      periodontal bone height reduction is observed. The impact of water pipe smoking
      is of the same magnitude as that of cigarette smoking.

PMID- 16104966
TI  - Open flap debridement with or without intentional cementum removal: a 4-month
      follow-up.
AB  - OBJECTIVES: The aim of this study was to investigate the influence of cementum
      removal on periodontal repair. MATERIAL AND METHODS: Forty subjects with chronic
      periodontitis and presenting, at least, two proximal sites in anterior teeth
      (upper or lower) with probing depth > or =5 mm were selected. After oral hygiene
      instructions and ultrasonic supragingival instrumentation, the subjects were
      randomly assigned for one of the following groups: CIC, scaled with Gracey
      curettes; CIUS, scaled with ultrasonic device; CDC, calculus deattachment with
      Gracey curettes and brushing with saline solution; and CDUS, calculus
      deattachment with ultrasonic device and brushing with saline solution. Full
      thickness flaps were reflected and the instrumentation was performed with a
      clinical microscope. Probing depth (PD), relative gingival margin level (RGML)
      and relative attachment level (RAL) were registered at five experimental periods:
      baseline and 30, 60, 90 and 120 days postoperative. RESULTS: All the approaches
      were able to markedly reduce the PD values from the baseline to the other
      evaluation periods (p<0.0001). The increase in RGML values was statistically
      significant only for the CDUS group. There were no statistically significant
      differences between the baseline and postoperative values in all groups for the
      RAL changes. The changes in RAL were statistically significant only among the
      groups CDC and CDUS (p<0.0001). CONCLUSION: The conventional scaling and root
      planing and the calculus deattachment were effective in reducing the probing
      depth values, regardless of the instrumentation method.

PMID- 16104967
TI  - Effects of phase I periodontal treatment on gingival crevicular fluid levels of
      matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of phase I
      periodontal treatment on gingival crevicular fluid (GCF) levels of matrix
      metalloproteinase (MMP)-3 and tissue inhibitors of metalloproteinase (TIMP)-1.
      METHODS: Plaque index, gingival index, pocket depth and clinical attachment loss
      were recorded and GCF samples were collected from 20 chronic periodontitis (CP)
      patients and 20 periodontally healthy controls (C) before treatment. CP patients
      received phase I periodontal treatment and all clinical parameters were recorded
      and GCF samples were collected once more after treatment. Assays were performed
      by an enzyme-linked immunosorbent assay. RESULTS: All of the clinical parameters
      improved significantly after the therapy (p<0.05). Baseline GCF levels of MMP-3
      were significantly higher than C and that level was reduced significantly by
      treatment compared with baseline levels (p<0.05). Baseline GCF levels of TIMP-1
      were lower than post-treatment levels and C (p<0.05). GCF levels of TIMP-1
      increased significantly by treatment compared with baseline levels (p<0.05).
      CONCLUSION: This study shows that the clinical improvements after phase I
      periodontal therapy are accompanied by reduction in MMP-3 and increasing in TIMP
      1 GCF levels.

PMID- 16104968
TI  - Periodontal treatment of two siblings with juvenile hyaline fibromatosis.
AB  - BACKGROUND AND AIM: Juvenile hyaline fibromatosis (JHF) is an autosomal recessive
      disease that presents with multiple subcutaneous nodular tumours, gingival
      fibromatosis, flexion contractures of the joint and hyaline material accumulation
      in extracellular area. Recently, the causative gene for JHF, capillary
      morphogenesis protein 2 (CMG2) was identified. In this case report, periodontal
      status, treatment and follow-up together with histopathologic evaluation of
      gingival tissue specimens and mutation screening of two JHF cases are presented.
      CASE REPORTS: A 10-year-old female (case 1) and her 3-year-old brother (case 2)
      were first examined in our department with a complaint of gingival hyperplasia in
      1991. Symptoms of the disease were detected in two of four siblings in the
      family. Several gingivectomy operations were carried out over 11 years with
      hygiene motivation and initial phase therapy. After the last gingivectomy
      operation in 2002, the patients were reviewed frequently. RESULTS AND
      CONCLUSIONS: Although there was linear marginal gingival inflammation, no
      remarkable enlargement was noted at last appointment. Histopathological findings
      showed increased amounts of subepithelial nodular connective tissue, thinned
      epithelial mucosa, separated inter-cellular bridges and decreased numbers of
      connective tissue cells in gingival tissue samples. Electron microscopic
      examinations supported the histopathological findings. Mutation screening of CMG2
      demonstrated that the siblings were homozygous for a pathogenic missense
      mutation, V386F. Our clinical findings demonstrate that gingivectomy is useful
      and frequent periodontal visits are important for maintaining oral hygiene and
      decreasing growth rate of gingiva in JHF.

PMID- 16104969
TI  - Gorham's disease of the mandible mimicking periodontal disease on radiograph.
AB  - BACKGROUND: Gorham's disease is a rare disorder characterized by spontaneous and
      progressive osteolysis of one or more skeletal bones. The radiographic findings
      associated with Gorham's disease are particularly dramatic, as in some cases a
      complete resorption of the involved bone can occur, leading to the definition of
      phantom bone, vanishing bone, or disappearing bone disease. MATERIAL AND METHODS:
      A 24-year-old female patient with a previous diagnosis of periodontal disease and
      progressive mandibular alveolar bone loss was referred to our Oral Medicine
      section. The initial radiographic picture showed infrabony defects and horizontal
      bone loss. RESULTS: After further extensive local and systemic evaluation,
      including histopathological, laboratory and imagine techniques investigations,
      the patient was diagnosed to be affected by Gorham's disease. Meanwhile the
      progression of the osteolytic process had caused the loosening of all the left
      mandibular teeth and a pathologic fracture. Appropriate medical therapy was
      successful in stabilizating the resorptive process, with no evidence of further
      progressive disease. CONCLUSIONS: When Gorham's disease involves the mandible,
      the role of the periodontologist is extremely important in diagnosing promptly
      the disorder and preventing the functional and aesthetic consequences of advanced
      and extensive bone loss. Gorham's disease should be included among the pathologic
      entities mimicking periodontal disease on radiograph, such as inflammatory
      disease (e.g. osteomyelitis), endocrine disease (e.g. hyperparathyroidism), intra
      osseous malignancies or metastases, lymphoma, histiocytosis X, mainly
      eosinophilic granuloma, infective process (e.g. tuberculosis and actinomycosis),
      odontogenic tumours.

PMID- 16104971
TI  - A comparison between a smooth wire and a K-file in removing artificially placed
      dentine debris from root canals in resin blocks during ultrasonic irrigation.
AB  - AIM: To compare the efficacy of a smooth wire with a conventional K-file, in
      removing dentine debris from grooves in root canals made in resin blocks, during
      ultrasonic irrigation. METHODOLOGY: Each resin block containing a standard
      simulated canal was split longitudinally through the canal, forming two halves.
      In one canal wall, a standard groove 4 mm in length, 0.2 mm in width and 0.5 mm
      in depth was cut 2-6 mm from the apical end of the canal, to simulate
      uninstrumented canal extensions. Each groove was filled with fresh dentine debris
      mixed with 2% NaOCl to simulate a situation when dentine debris accumulates in
      uninstrumented canal extensions. Each canal was reassembled by joining the two
      halves of the resin block by means of wires and sticky wax. In each canal
      ultrasonic irrigation was performed for 3 min using 2% NaOCl as irrigant. In one
      group (n = 20) a conventional K-file size 15 was used. In the other group (n =
      20) a smooth wire was used which had the same length and diameter as the size 15
      K-file. Before and after irrigation, images of each half of the canal with a
      groove were taken, using a microscope and a digital camera, after which they were
      scanned into a PC as TIFF images. The quantity of dentine debris in the groove
      was evaluated using a scoring system: the higher the score, the larger the amount
      of debris remaining. The score data were analysed by means of the Mann-Whitney U
      test. RESULTS: After ultrasonic irrigation, the debris was completely removed
      from the groove in 35 canals (87.5%), and there was no significant difference
      between the groups (P = 0.429). CONCLUSIONS: Using a smooth wire during
      ultrasonic irrigation is as effective as a size 15 K-file in removal of
      artificially placed dentine debris in grooves in simulated root canals in resin
      blocks.

PMID- 16104972
TI  - Periapical biomechanics and the role of cyclic biting force in apical retrograde
      fluid movement.
AB  - AIM: To investigate the stress distribution pattern in the periapical region
      caused by biting forces and to study the role of cyclic biting loads on
      periapical fluid movement. METHODOLOGY: In the first part, a digital photoelastic
      experiment was conducted to study stress distribution in the periapical region.
      In the second, 20 maxillary central incisors were selected and divided into three
      main groups: normal intact teeth (group 1), tooth specimens in which the root
      canal was enlarged and maintained wet (group 2), and tooth specimens in which the
      root canal was enlarged and maintained dry (group 3). The tooth specimens were
      placed in a polycarbonate support with a cavity filled with a sponge soaked in
      methylene blue solution to simulate a periapical defect with exudate. During
      testing, the specimens were placed in a water bath at 37 degrees C, and were
      loaded cyclically with a load of 20 N, at a rate of 72 cycles min(-1), to a
      maximum of 20,000 cycles. The specimens were then sectioned and evaluated for
      retrograde fluid movement using light microscopy. The data were analysed using
      one-way anova (post hoc tests). RESULTS: Digital photoelastic experiments showed
      that the compression of teeth produced bending stresses in the periapical region.
      Testing with cyclic loads demonstrated retrograde fluid movement into the apical
      portion of the root canal and extraradicular region in all groups. There was a
      significant difference amongst the apical retrograde fluid movement displayed by
      different groups (<0.01). Group 2, in which the root canal was enlarged and
      maintained wet showed maximum retrograde fluid movement, whilst group 3, in which
      the root canal was enlarged and maintained dry showed the least retrograde fluid
      movement. CONCLUSIONS: Biting forces would cause bending of the periapical bone
      and cyclic biting forces would contribute to retrograde fluid movement into the
      root canal space and extraradicular region.

PMID- 16104973
TI  - Cytotoxicity of MTA and Portland cement on human ECV 304 endothelial cells.
AB  - AIM: To evaluate the cytotoxic effects of two brands of mineral trioxide
      aggregate (MTA) (Pro-Root MTA and MTA Angelus) and Portland cement (PC) on the
      human ECV 304 endothelial cell line. METHODOLOGY: Endothelial ECV 304 cells were
      incubated at 37 degrees C in an atmosphere of 95% air, 5% carbon dioxide and 100%
      humidity for 7 days and grown in F12 medium supplemented with 10% fetal bovine
      serum with 50 microg mL(-1) of gentamicin sulphate. Effects of the materials on
      mitochondrial functions were measured by a colorimetric assay. At each
      experimental time interval (24, 48 and 72 h), a dimethyl-thiazol-diphenyl
      tetrazolium bromid assay was conducted to measure cell viability. All assays were
      repeated three times to ensure reproducibility. Results were expressed as average
      absorbance (A(570/nm)) +/- SD and the data were analysed statistically by one-way
      analysis of variance and the Bonferroni post-test. A P-value < 0.05 was
      considered statistically significant. RESULTS: No statistically significant
      difference was shown between any of the experimental materials (P > 0.05).
      CONCLUSIONS: The two brands of MTA analysed, as well as the PC, initially showed
      a similar elevated cytotoxic effect that decreased gradually with time allowing
      the cell culture to become reestablished.

PMID- 16104974
TI  - A comparative study of Endoflare-Hero Shaper and Mtwo NiTi instruments in the
      preparation of curved root canals.
AB  - AIM: To analyse the shaping ability of two new NiTi rotary systems in molar
      curved canals. METHODOLOGY: Thirty molar root canals with curvatures from 24
      degrees to 69 degrees were divided into two groups that were balanced in terms of
      curvature. The canals in one group were shaped using the Mtwo (Sweden & Martina,
      Padova, Italy) and the canals in the other group using the Endoflare-Hero Shaper
      (Micro-Mega, Besancon, France) in a modified sequence. Pre- and post
      instrumentation X-rays were taken using a radiographic platform, with a contrast
      medium being used to enhance canal opacity. The dentine removed at five positions
      along the canals, the symmetry of canal shaping and the presence of aberrations
      were analysed through computer-aided measurements. The instrument failures, the
      working time and the changes in working length were also recorded. The Mann
      Whitney U-test was used for statistical analyses. RESULTS: Both systems produced
      uniform dentine removal and symmetrical canal shapes; there was no significant
      difference between the systems (P > 0.05). In the apical region, preparations
      were centred in the canal. A mean loss of working length of 0.55 mm for Mtwo and
      0.58 mm for Endoflare-Hero Shaper was detected, with no significant differences
      between the instruments (P > 0.05). No aberrations were seen and no instruments
      separated. The mean working time was 124.4 s for the Mtwo system and 141.3 s for
      the Endoflare-Hero Shaper but this difference was not statistically significant
      (P > 0.05). CONCLUSION: The systems tested in this study were effective in
      shaping curved canals in extracted teeth.

PMID- 16104975
TI  - The imaging of root canal obturation using micro-CT.
AB  - AIM: To examine the potential and accuracy of micro-computed tomography (micro
      CT) for imaging of filled root canals. METHODOLOGY: The root canals of five
      extracted maxillary teeth were shaped manually with K-files. After irrigation and
      drying, the root canals were filled by lateral condensation using gutta-percha
      cones and AH plus (Dentsply Maillefer, Ballaigues, Switzerland) as sealer. The
      filled root canals were examined by micro-CT at resolutions <11 microm. Three
      dimensional reconstructions of the root canal fillings were made. The roots were
      sectioned histologically and standard photographs of the sectioned surfaces were
      taken. Digitized photographic images and the corresponding micro-CT sections were
      correlated qualitatively by superimposition. Quantitative morphometric data were
      obtained with respect to the surface area of the root canal filling and the
      individual gutta-percha points of the histological and the micro-CT sections.
      Pearson correlation coefficients were calculated. RESULTS: There was a good
      qualitative correlation between the images from the histological and the micro-CT
      sections. The fillings were clearly differentiated from the root canal walls.
      Individual gutta-percha cones and sealer were discernable. Pearson correlation
      coefficients showed a highly significant correlation between the two methods (P <
      0.001) with respect to the area of the complete root canal filling (r = 0.992)
      and the gutta-percha cones (r = 0.968). CONCLUSIONS: The micro-CT technique was a
      highly accurate and nondestructive method for the evaluation of root canal
      fillings and its constituents. Qualitative and quantitative correlation between
      histological and micro-CT examination of root canal fillings was high.

PMID- 16104976
TI  - Influence of different types of automated devices on the shaping ability of
      rotary nickel-titanium FlexMaster instruments.
AB  - AIM: To compare the shaping ability of rotary FlexMaster nickel-titanium
      instruments in simulated curved canals and in curved canals of extracted teeth
      when set into permanent rotation with three different torque-limited automated
      devices. METHODOLOGY: Root canal instrumentation was performed with three
      different torque-limited automated devices (ENDOadvance, SIRONiTi and Endo IT
      motor) by FlexMaster nickel-titanium instruments up to size 35. Simulated canals:
      28 degree and 35 degree curved canals in resin blocks (n = 20 canals in each
      group) were prepared. Pre- and post-instrumentation images were recorded and
      assessment of canal shape was completed with a computer image analysis program.
      Extracted teeth: A total of 60 curved root canals were divided into three groups,
      which were balanced with respect to the angle and the radius of canal curvature.
      Straightening of the canal curvatures was determined with a computer image
      analysis program. Incidence of canal aberrations, preparation time, changes of
      working length and instrument failures were recorded both in simulated and real
      canals. RESULTS: In simulated and real canals, instrumentation with Endo IT was
      significantly faster than with SIRONiTi (P < 0.05). With respect to canal
      aberrations in simulated canals, there were no significant differences between
      the devices (P > 0.05), even though more aberrations were created with
      ENDOadvance and SIRONiTi. In real canals, the Endo IT motor resulted in
      significantly less straightening during instrumentation (P < 0.05) than SIRONiTi.
      A total of three instruments separated (one file in each group) during the
      enlargement of 35 degree curved simulated canals. All systems maintained working
      distance well. CONCLUSIONS: All systems respected original root canal curvature
      well and were safe, indicating that torque-limited rotation handpieces are
      suitable for preparing curved root canals.

PMID- 16104977
TI  - Shaping ability of two rotary instruments in simulated canals: stainless steel
      ENDOflash and nickel-titanium HERO Shaper.
AB  - AIM: To compare the shaping ability of two rotary instruments in simulated curved
      canals: stainless steel ENDOflash Files (KaVo, Biberach, Germany) and the
      recently introduced nickel-titanium HERO Shaper instruments (Micro-Mega,
      Besancon, France). METHODOLOGY: Simulated root canals with 35 degree curves in
      resin blocks were prepared to size 30, .04 taper (HERO Shaper) using a crowndown
      technique or size 30, .02 taper (ENDOflash) using a rotary motion and a rotation
      speed of 400 or 250 rpm respectively. In both groups, irrigation was performed
      with 1 mL distilled water after each instrument size and Glyde (Dentsply
      Maillefer, Ballaigues, Switzerland) were used. Canals (n = 17 per group) were
      scanned before, during and after preparation. The assessment of preparation shape
      was carried out with a computer image analysis program. Material removal was
      measured at seven points beginning 1 mm from the end-point of the canal.
      Statistical analysis was performed using Wilcoxon's test and Fisher's exact test
      (P < 0.05). RESULTS: No instrument fractures, apical blockage or loss of working
      length (WL) occurred. More zips (10 vs. 4) and more strippings (17 vs. 0) were
      created with ENDOflash compared with the HERO Shaper. There were significant
      differences in terms of the amount of resin removed on the inner wall of the
      curvature obtained with the two instruments (P < 0.0001). On average, HERO Shaper
      instruments removed material more evenly on the outer and inner wall of the
      curvature. Considering the different points of measurement, there were
      significant differences between the two systems both on the inner and outer walls
      at WL-1, 2, 5 and 6 mm (P < 0.05). The HERO Shaper had a more centred enlargement
      compared with the ENDOflash. CONCLUSIONS: Stainless steel rotary ENDOflash
      instruments did not perform as well as HERO Shaper instruments and created an
      increased risk of root canal transportation. Nickel-titanium rotary HERO Shaper
      instruments maintained the original curvature significantly better.

PMID- 16104978
TI  - A laboratory comparison of three imaging systems for image quality and radiation
      exposure characteristics.
AB  - AIM: To measure and compare the relationships between image quality and X-ray
      exposure for three types of intraoral imaging system (conventional film, phosphor
      plate system and CCD-based system). METHODOLOGY: Kodak 'Insight' F-speed film,
      Digora FMX (phosphor plate system) and Visualix USB (CCD system) were used to
      produce series of radiographic images of two tooth-bearing jaw specimens
      (maxillary molar and mandibular molar regions) at a range of X-ray exposures from
      10 ms to 2000 ms (all at 6 mA and 60 kV). Digital images were viewed from a
      computer monitor and films viewed on a conventional light box. Five observers
      scored each image using a five-point subjective image quality scale (0-4).
      RESULTS: Optimum image quality (4) was seen for conventional film. Neither
      digital system achieved this score at any exposure, achieving in both cases a
      maximum mean score of 3.1 (adequate visualization). The two digital systems,
      however, provided adequate visualization at substantially lower exposure times.
      Dose reduction over conventional film for maximum quality images with Visualix
      USB was 20%, but for Digora FMX it was 70%. All three systems gave acceptable
      (quality score of two or higher) images over a broad range of exposures.
      CONCLUSIONS: In terms of subjective image quality, F-speed film performed better
      than the two digital systems, but this must be weighed against the ability of the
      two digital systems to give adequate image quality at lower radiation doses.

PMID- 16104979
TI  - A temporary filling material may cause cusp deflection, infractions and fractures
      in endodontically treated teeth.
AB  - AIM: To test the hypothesis that Coltosol F might cause infractions and cusp
      fracture in root-filled teeth because of material expansion. METHODOLOGY: Thirty
      two extracted human molar teeth were root filled and prepared with mesial
      occlusal-distal (MOD) cavities with or without undercuts. The specimens were
      filled proximally with glass-ionomer cement and then occlusally with either
      Coltosol F or zinc oxide eugenol (ZOE). The tooth specimens were kept in water at
      37 degrees C for a period of 20 days, and every second day the intercusp distance
      (ICD) of each specimen was measured in a travelling microscope, and the number of
      infraction lines as well as fractures were noted. RESULTS: The number of
      infraction lines increased in teeth filled with Coltosol F. Between day 8 and 16,
      seven of 16 teeth filled with Coltosol F showed fracture and exhibited a mean
      increase in ICD of 316 +/- 156 microm. Teeth filled with ZOE did not show an
      increase in number of infraction lines or in ICD, and none showed fracture.
      CONCLUSIONS: The hygroscopic expansion of Coltosol F in a cavity may lead to cusp
      deflection, infraction development and fracture. Masticatory forces will in vivo
      aggravate this unfavourable condition. The material is not recommended for
      temporary filling in root-filled teeth except for a few days.

PMID- 16104980
TI  - Effect of customization of master gutta-percha cone on apical control of root
      filling using different techniques: an ex vivo study.
AB  - AIMS: (i) To compare the prevalence of extrusion of root filling material when
      placed using different root filling techniques, with or without customization of
      the master gutta-percha (GP) cone; and (ii) to investigate the effects of some
      factors influencing root filling extrusion and presence of voids. METHODOLOGY: A
      total of 180 roots were selected, prepared and randomly allocated to three
      groups. Five general dental practitioners performed the root fillings; each
      filled one group of roots (n = 60) using each of three techniques; 'cold lateral
      compaction' (n = 20), 'warm vertical compaction' (n = 20) and 'continuous-wave'
      (n = 20) techniques. For each obturation technique, the master GP cone was
      customized using chloroform in 10 samples. Two groups of the roots were recycled
      to allow all five operators to fulfill their remit. Two observers, blind to
      operator and obturation technique, examined the radiographs (master apical file,
      post-obturation) to determine the presence of root filling extrusion and voids
      within the apical 5 mm, independently. Root filling extrusion was also confirmed
      by direct inspection of the root apex after obturation. The data were analysed
      using logistic regression models. RESULTS: A total of 300 root fillings were
      performed; nine were excluded from the analysis. Most of the root fillings (80%,
      n = 233) were placed within 0.5 mm of the working length; only 20% (n = 58) were
      placed >0.5 mm beyond the working length. The odds of prevalence of extrusion
      (>0.5 mm) were significantly reduced by about 50% when cold lateral compaction or
      customization of GP were used. One operator produced 2.5 times more extruded root
      fillings than others. Curvature & length of root canal, apical size of prepared
      canal, as well as operator's preferred obturation technique had no significant
      influence on the prevalence of extrusion. Customization of GP was the sole factor
      to significantly reduce the prevalence of voids within the apical 5 mm of working
      length. CONCLUSIONS: Root filling extrusion was significantly influenced by
      'operator' and was reduced by cold lateral compaction and customization of the
      master cone. Customization of master cone was the only factor that reduced voids
      apically.

PMID- 16104981
TI  - Effect of E. faecalis on the release of serine proteases elastase and cathepsin
      G, and collagenase-2 (MMP-8) by human polymorphonuclear leukocytes (PMNs).
AB  - AIM: To measure the release of hydrolytic enzymes [elastase, cathepsin G and
      collagenase-2 (MMP-8)] from human polymorphonuclear leukocytes (PMNs) during
      interaction with strains of Enterococcus faecalis isolated from endodontic
      infections. METHODOLOGY: Six E. faecalis strains isolated from treatment
      resistant cases of apical periodontitis were included in the study. Overnight
      cultures of the microbes were used for the experiments. PMNs were isolated using
      the Ficoll Paque technique, and their vitality was assessed throughout the
      experiments by the Trypan Blue exclusion test. A known amount of microbes and
      PMNs were mixed in PBS at +37 degrees C in air, and the release of elastase,
      cathepsin G and MMP-8 was measured at 0, 20, 60 and 120 min after initiation of
      incubation. The activities of elastase and cathepsin G were analysed by
      spectrophotometer assays using specific synthetic peptide substrates, and MMP-8
      by western immunoblotting quantitated by computer densitometry. PMNs incubated in
      buffer without any added microbes served as negative controls, cells incubated
      with 5 ng mL(-1) phorbol myristic acetate (PMA) served as a positive control. The
      95% confidence interval was used to compare the relative amount of elastase and
      cathepsin G released from the samples. RESULTS: One E. faecalis strain induced a
      similar or higher elastase, cathepsin G and MMP-8 release than the positive
      control, whereas the other five strains induced only moderate or no release of
      the three enzymes examined as compared with the negative and positive controls.
      Western immunoblot revealed that released MMP-8 had molecular sizes of 60 and 75
      kDa representing active and latent forms of MMP-8. In addition, >110 kDa high
      molecular size and a fragmented 20-30 kDa MMP-8 species could be observed.
      CONCLUSIONS: The majority of the E. faecalis strains induced little or no release
      of hydrolytic enzymes from the PMN cells. The finding may partly explain the
      clinical observation that root canal infections dominated by E. faecalis are
      usually symptom free.

PMID- 16104982
TI  - Chlamydia trachomatis: time for screening?
AB  - Genital Chlamydia trachomatis infection is the leading cause of bacterial
      sexually transmitted disease in industrialised countries, particularly among
      young people. The consequences of chlamydial infection may involve urethritis,
      cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor
      infertility, epididymitis and prostatitis. In addition, chlamydial infection
      increases the risk of acquisition of human immunodeficiency virus and has been
      associated with cervical cancer. Although screening programmes exist in a number
      of countries, the continuously increasing prevalence of chlamydial infections
      demonstrates the necessity for health authorities to establish effective
      screening policies, and the importance of defining a comprehensive European
      screening policy is emerging.

PMID- 16104983
TI  - Antimicrobial therapy for pulmonary pathogenic colonisation and infection by
      Pseudomonas aeruginosa in cystic fibrosis patients.
AB  - Pseudomonas aeruginosa colonisation has a negative effect on pulmonary function
      in cystic fibrosis patients. The organism can only be eradicated in the early
      stage of colonisation, while reduction of bacterial density is desirable during
      chronic colonisation or exacerbations. Monthly, or at least 3-monthly,
      microbiological culture is advisable for patients without previous evidence of P.
      aeruginosa colonisation. Cultures should be performed at least every 2-3 months
      in patients with well-established colonisation, and always during exacerbations
      or hospitalisations. Treatment of patients following the first isolation of P.
      aeruginosa, but with no clinical signs of colonisation, should be with oral
      ciprofloxacin (15-20 mg/kg twice-daily for 3-4 weeks) plus inhaled tobramycin or
      colistin (intravenous treatment with or without inhaled treatment can be used as
      an alternative), while patients with acute infection should be treated for 14-21
      days with high doses of two intravenous antimicrobial agents, with or without an
      inhaled treatment during or at the end of the intravenous treatment. Maintenance
      treatment after development of chronic P. aeruginosa infection/colonisation
      (pathogenic colonisation) in stable patients (aged>6 years) should be with
      inhaled tobramycin (300 mg twice-daily) in 28-day cycles (on-off) or, as an
      alternative, colistin (1-3 million units twice-daily). Colistin is also a
      possible choice for patients aged<6 years. Treatment can be completed with oral
      ciprofloxacin (3-4 weeks every 3-4 months) for patients with mild pulmonary
      symptoms, or intravenously (every 3-4 months) for those with severe symptoms or
      isolates with ciprofloxacin resistance. Moderate and serious exacerbations can be
      treated with intravenous ceftazidime (50-70 mg/kg three-times-daily) or cefepime
      (50 mg/kg three-times-daily) plus tobramycin (5-10 mg/kg every 24 h) or amikacin
      (20-30 mg/kg every 24 h) for 2-3 weeks. Oral ciprofloxacin is recommended for
      patients with mild pulmonary disease. If multiresistant P. aeruginosa is
      isolated, antimicrobial agents that retain activity are recommended and
      epidemiological control measures should be established.

PMID- 16104984
TI  - Assessment of fluorescent amplified fragment length polymorphism analysis for
      epidemiological genotyping of Legionella pneumophila serogroup 1.
AB  - This study assessed the reproducibility and epidemiological concordance of double
      enzyme fluorescent amplified fragment length polymorphism (fAFLP) analysis for
      genotyping of Legionella pneumophila serogroup (sg) 1. fAFLP fragment analysis
      was performed on three different sequencing platforms (one gel- and two capillary
      based) in different laboratories with a well-characterised set of 50 strains of
      L. pneumophila sg 1. fAFLP data were analysed with the Pearson correlation
      similarity coefficient, using a range of parameters, and dendrogram outputs were
      converted to arbitrary types after selection of a specified percentage similarity
      threshold. The results obtained were compared with those obtained by the standard
      non-fluorescent AFLP method and were found to be broadly concordant. Using
      optimised settings for each fAFLP method to analyse the panel of 50 strains,
      epidemiological concordance (E) and reproducibility (R) values of 1.00 were
      obtained, and the number of types ranged from nine to 15, compared with E=1.00
      and R=1.00, with 16 types, for the non-fluorescent AFLP protocol. The study
      demonstrated the potential of fAFLP for typing strains of L. pneumophila sg 1 on
      all three platforms; however, inter-platform comparison of fAFLP data was not
      achieved. fAFLP analysis may have a role in the fingerprinting of multiple
      isolates during Legionella outbreak investigations, but further work is required
      before type designations and identification libraries can be developed.

PMID- 16104985
TI  - Rapid diagnosis of human brucellosis by SYBR Green I-based real-time PCR assay
      and melting curve analysis in serum samples.
AB  - The aim of this study was to develop a LightCycler-based real-time PCR (LC-PCR)
      assay and to evaluate its diagnostic use for the detection of Brucella DNA in
      serum samples. Following amplification of a 223-bp gene sequence encoding an
      immunogenetic membrane protein (BCSP31) specific for the Brucella genus, melting
      curve and DNA sequencing analysis was performed to verify the specificity of the
      PCR products. The intra- and inter-assay variation coefficients were 1.3% and
      6.4%, respectively, and the detection limit was 5 fg of Brucella DNA (one genome
      equivalent). After optimisation of the PCR assay conditions, a standard curve was
      obtained with a linear range (correlation coefficient=0.99) over seven orders of
      magnitude from 10(7) to 10 fg of Brucella DNA. The LC-PCR assay was found to be
      91.9% sensitive and 95.4% specific when tested with 65 negative control samples
      and 62 serum samples from 60 consecutive patients with active brucellosis. The
      assay is reproducible, easily standardised, minimises the risk of infection in
      laboratory workers, and has a total processing time of <2 h. It could therefore
      form a promising and practical approach for the rapid diagnosis of human
      brucellosis.

PMID- 16104986
TI  - Seroprevalence of Toxoplasma gondii in northern Greece during the last 20 years.
AB  - The seroprevalence of Toxoplasma gondii in the northern Greek population was
      determined in 1984, 1994 and 2004, and changes during this period were
      investigated. In total, 1014, 812 and 958 sera from individuals aged 1 day to 70
      years were examined in 1984, 1994 and 2004, respectively, for IgG and IgM anti
      Toxoplasma antibodies with the standard immunofluorescence assay (IFA) and
      microparticle enzyme immunoassay (MEIA). In individuals positive for IgM-specific
      antibodies, primary infection with Toxoplasma was diagnosed on the basis of the
      Toxoplasma serological profile (IFA, MEIA, conventional IgM and IgA ELISAs,
      immunosorbent agglutination assay and IgG avidity test). The prevalence of IgG
      specific antibodies in the general population was 37%, 29.9% and 24.1% in 1984,
      1994 and 2004, respectively, and was 35.6%, 25.6% and 20%, respectively, in women
      of reproductive age (15-39 years). The incidence of Toxoplasma infection, based
      on cases of primary infection and the annual seroconversion rate for the general
      population, was estimated to be 1.25% and 1.1% in 1984, 1.05% and 0.93% in 1994,
      and 0.85% and 0.8% in 2004. The significant decline in prevalence, and the shift
      towards an older age group, observed during this period could be explained by the
      improved socio-economic situation. The high (80%) proportion of women of
      reproductive age susceptible to Toxoplasma infection, with an estimated 90-200
      neonates infected in utero annually, seems to present a potential risk to public
      health. Education of the public and prophylactic measures may become increasingly
      important.

PMID- 16104987
TI  - Incidence and clinical significance of anaerobic bacteraemia in cancer patients:
      a 6-year retrospective study.
AB  - Recent studies have shown that anaerobes account for 0.5-9% of all episodes of
      bacteraemia in hospitalised patients, with variations according to geographical
      location and demographic characteristics, most notably age, but few data are
      available for cancer patients. This study investigated retrospectively the
      incidence of anaerobic bacteraemia in cancer patients who received non-surgical
      treatment over a 6-year period at a tertiary oncology centre. Gastrointestinal
      (27%) and haematological (29%) malignancies were the most common underlying
      diseases. Among 45 isolates of anaerobic bacteria recovered from 45 patients,
      Bacteroides spp. and Clostridium spp. were the most frequent pathogens (60% and
      22%, respectively). Twenty episodes of bacteraemia were polymicrobial, most
      frequently with aerobic Gram-negative bacilli (18 cases). The mortality rate for
      patients with adequate antimicrobial therapy from the outset was 14%, compared
      with 63% for patients who were not treated adequately at any time.

PMID- 16104988
TI  - Predictive value of soluble haemoglobin scavenger receptor CD163 serum levels for
      survival in verified tuberculosis patients.
AB  - Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected
      tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3
      years (range 0-6.4 years). In 113 cases, the diagnosis of TB was verified by
      positive sputum microscopy and/or culture. Among the verified TB cases, a
      decreased survival rate was found in 27 patients with sCD163 levels above the
      upper reference limit (3.95 microg/mL). The difference in survival was
      significant during TB treatment (log rank, p<0.02) and after long-term follow-up
      (log rank, p<0.001). The decrease in survival rate during TB treatment remained
      significant in a multivariate Cox model controlling for human immunodeficiency
      virus (HIV) status, age and gender, with a mortality increase of 1.19 (95% CI,
      1.04-1.36) per microg of sCD163, and a hazard ratio (HR) for sCD163 levels above
      the upper reference limit of 4.18 (95% CI, 1.06-16.4). The difference was not
      significant after excluding patients with concomitant HIV-1 and HIV-2 infection
      in Kaplan-Meier analyses (log rank, p 0.11). In contrast, the difference in
      survival remained significant in Kaplan-Meier analyses after long-term follow-up,
      even after excluding patients with concomitant HIV-1 and HIV-2 infection (log
      rank, p 0.002). In the Cox model, the mortality increase per microg of sCD163 was
      1.27 (95% CI, 1.14-1.40), with an HR for elevated sCD163 levels of 2.85 (95% CI,
      1.44-5.63). The HRs for concomitant HIV-1 and HIV-2 infection were 6.92 (95% CI,
      3.28-14.58) and 2.48 (95% CI, 1.09-5.67), respectively. Thus, sCD163 levels
      appeared to be an independent predictor of survival in verified TB patients.

PMID- 16104989
TI  - A comparative randomised study of valacyclovir vs. oral ganciclovir for
      cytomegalovirus prophylaxis in renal transplant recipients.
AB  - An open, prospective, randomised study was conducted to compare the safety and
      efficacy of valacyclovir vs. oral ganciclovir for cytomegalovirus (CMV)
      prophylaxis in renal transplant recipients. Eighty-three renal transplant
      recipients were assigned randomly to receive valacyclovir (n=43) or oral
      ganciclovir (n=40) for the first 3 months after transplantation. Both groups were
      similar in terms of demographics, primary renal disease, graft source, HLA
      matching, immunosuppressive therapy and donor-recipient CMV antibody status. CMV
      infection was diagnosed by detection of virus DNA in plasma with the Amplicor CMV
      Test. CMV disease was observed in only one patient belonging to the ganciclovir
      group, who developed enterocolitis 6 months post-transplantation. No difference
      was observed between the two treatment groups with respect to detection of CMV
      DNA, virus infections other than CMV, acute rejection episodes, and serum
      creatinine levels at 3 and 6 months following transplantation. An increased
      number of bacterial infections was noted in the ganciclovir group (p 0.003). No
      adverse reactions with either treatment were reported. The estimated cost of
      valacyclovir treatment was 20% higher than that of ganciclovir treatment.
      Overall, both valacyclovir and oral ganciclovir were found to be effective and
      safe for CMV prophylaxis in renal transplant recipients. Decisions regarding
      prophylactic regimens should include additional criteria, such as cost or
      possible development of resistance.

PMID- 16104990
TI  - Nationwide study of recurrent invasive pneumococcal infections in a population
      with a low prevalence of human immunodeficiency virus infection.
AB  - Recurrent invasive infections caused by Streptococcus pneumoniae are rare, and
      often considered to be indicative of serious underlying illness. However, the
      prevalence of this problem, and the relevance of specific predisposing
      conditions, can be hard to assess, since many of the studies are based on
      specific risk groups. A population-based study of recurrent invasive pneumococcal
      disease in Iceland during the 30-year period 1975-2004 was performed. Clinical
      information, including mortality and vaccine use, was analysed retrospectively.
      Invasive pneumococcal isolates were serotyped and susceptibility testing was
      performed. During this period, 36 (4.4%) of 819 patients who survived an initial
      infection experienced recurrence, with a median time between episodes of 9.7
      months. Pneumonia with bacteraemia was the most common clinical diagnosis (48% of
      cases), followed by bacteraemia without a clear focus (21%) and meningitis (13%).
      Most (94%) of the patients had identifiable predisposing conditions, most
      commonly, multiple myeloma in adults, and antibody deficiencies in children.
      Compared with children, adults were more likely to present with pneumonia (65%
      vs. 18%; p 0.0001). No significant change in the 30-day mortality rate was
      observed during the three decades of the study. Only 26% of eligible patients
      received pneumococcal vaccination. Patients with recurrent invasive pneumococcal
      disease should be investigated thoroughly for underlying diseases. Greater use of
      pneumococcal vaccines should be encouraged among high-risk patients. More
      effective preventive and therapeutic measures are needed to improve outcomes.

PMID- 16104991
TI  - The selection of resistance to and the mutagenicity of different fluoroquinolones
      in Staphylococcus aureus and Streptococcus pneumoniae.
AB  - Two quinolone-susceptible Staphylococcus aureus and five quinolone-susceptible
      Streptococcus pneumoniae isolates were used to obtain in-vitro quinolone
      resistant mutants in a multistep resistance selection process. The
      fluoroquinolones used were ciprofloxacin, moxifloxacin, levofloxacin,
      gemifloxacin, trovafloxacin and clinafloxacin. The mutagenicity of these
      quinolones was determined by the Salmonella and the Escherichia coli
      retromutation assays. All quinolone-resistant Staph. aureus mutants had at least
      one mutation in the grlA gene, while 86.6% of quinolone-resistant Strep.
      pneumoniae mutants had mutations in either or both the gyrA and parC genes.
      Moxifloxacin and levofloxacin selected resistant mutants later than the other
      quinolones, but this difference was more obvious in Staph. aureus. Accumulation
      of the fluoroquinolones by Staph. aureus did not explain these differences, since
      levofloxacin and moxifloxacin accumulated inside bacteria to the same extent as
      clinafloxacin and trovafloxacin. The results also showed that moxifloxacin and
      levofloxacin had less mutagenic potency in both mutagenicity assays, suggesting a
      possible relationship between the selection of resistance to quinolones and the
      mutagenic potency of the molecule. Furthermore, gemifloxacin selected efflux
      mutants more frequently than the other quinolones used. Thus, the risk of
      developing quinolone resistance may depend on the density of the microorganism at
      the infection site and the concentration of the fluoroquinolone, and also on the
      mutagenicity of the quinolone used, with moxifloxacin and levofloxacin being the
      least mutagenic.

PMID- 16104992
TI  - Characterisation of fluoroquinolone-resistant clinical isolates of Streptococcus
      pyogenes in Barcelona, Spain.
AB  - Resistance mechanisms and clonal relationships were determined for six
      Streptococcus pyogenes isolates with low- or high-level ciprofloxacin resistance.
      Four isolates displayed reduced susceptibility to ciprofloxacin and levofloxacin
      and had alterations in ParC: Ser80-->Pro (isolate emm3.1); Ser79-->Ala (two
      isolates emm6.0); and a double substitution Ser79-->Phe and Ala121-->Val (isolate
      emm12.27). Two isolates (emm12.26) displayed high-level resistance to
      ciprofloxacin and levofloxacin, as well as to other quinolones. These isolates
      had the same double substitution in ParC as isolate emm12.27, and an additional
      substitution (Ser81-->Tyr) in GyrA. Resistance patterns, emm typing and
      sequencing of the quinolone resistance-determining regions defined two clusters
      containing three and two isolates, respectively.

PMID- 16104993
TI  - Comparison of strand displacement and ligase chain amplification for detection of
      Chlamydia trachomatis infection in urogenital specimens.
AB  - Two amplification tests for the diagnosis of Chlamydia trachomatis infection,
      namely the ligase chain reaction (LCx) and the strand displacement assay
      (ProbeTec), were compared using samples from 1183 patients at sexually
      transmitted disease clinics. The overall prevalence of positive results was 8.0%,
      with agreement between the two assays of 98.8%. For endocervical, urethral and
      male urine samples, agreement was 99.3%, 99.4% and 97.7%, respectively. For ten
      discrepant samples, alternative amplification assays suggested that the LCx and
      ProbeTec assays gave erroneous results in six and four cases, respectively.
      Inhibition of amplification was observed with three (0.25%) urine specimens.

PMID- 16104994
TI  - Human immunodeficiency virus and other sexually transmitted diseases in Cuban
      women.
AB  - A cross-sectional study was performed in 60 Cuban women of child-bearing age who
      were seropositive for human immunodeficiency virus (HIV) and 60 controls. Human
      papillomavirus (HPV) was identified most frequently, with oncogenic HPV serotypes
      16, 33 and 58 detected in HIV-positive patients, and serotypes 11, 33 and 51 in
      the controls (relative risk 4.41; 95% CI 2.21-8.29). Syphilis and hepatitis B and
      C viruses were detected exclusively in HIV-seropositive women (p<0.05). Sexually
      transmitted diseases (STDs) appeared to pose a substantial health problem,
      especially for HIV-positive women. Clinics should consider screening and
      treatment for STDs as part of their HIV prevention programmes.

PMID- 16104995
TI  - Evidence of transmission of verocytotoxin-producing Escherichia coli O111 from a
      cattle stable to a child.
AB  - Infections with verocytotoxigenic Escherichia coli (VTEC) other than O157 have
      been assumed to have the same epidemiology as those with VTEC O157, but the
      source of infection is rarely defined for sporadic cases. This report describes a
      child with VTEC O111:H- infection who was probably infected by playing in a
      cattle stable and/or by drinking raw milk from the cows in this stable. E. coli
      O111 isolates colonising the cattle were indistinguishable from the patient
      isolate by the use of serotyping, pulsed-field gel electrophoresis, and virulence
      profiling.

PMID- 16104996
TI  - Virulence Searcher: a tool for searching raw genome sequences from bacterial
      genomes for putative virulence factors.
AB  - There is often a delay between completion of a genome sequence and its
      publication, mainly because of the lengthy process of annotation. For most
      researchers, the raw sequence alone does not easily yield the rich information it
      contains. An online tool (Virulence Searcher) has been designed that enables
      scientists interested in bacterial pathogenesis to search sequences from
      unannotated bacterial genomes for putative genes encoding virulence factors. This
      will facilitate an immediate start on important research into bacterial disease
      without having to wait for the annotated sequence to be published.

PMID- 16104997
TI  - Difficulty in assaying colistin methanesulphonate.

PMID- 16104998
TI  - Implantable hemodynamic monitors: success in the pursuit of failure?

PMID- 16104999
TI  - Implant experience with an implantable hemodynamic monitor for the management of
      symptomatic heart failure.
AB  - INTRODUCTION: Management of congestive heart failure is a serious public health
      problem. The use of implantable hemodynamic monitors (IHMs) may assist in this
      management by providing continuous ambulatory filling pressure status for optimal
      volume management. METHODS AND RESULTS: The Chronicle system includes an
      implanted monitor, a pressure sensor lead with passive fixation, an external
      pressure reference (EPR), and data retrieval and viewing components. The tip of
      the lead is placed near the right ventricular outflow tract to minimize risk of
      sensor tissue encapsulation. Implant technique and lead placement is similar to
      that of a permanent pacemaker. After the system had been successfully implanted
      in 148 patients, the type and frequency of implant-related adverse events were
      similar to a single-chamber pacemaker implant. R-wave amplitude was 15.2 +/- 6.7
      mV and the pressure waveform signal was acceptable in all but two patients in
      whom presence of artifacts required lead repositioning. Implant procedure time
      was not influenced by experience, remaining constant throughout the study.
      CONCLUSION: Based on this evaluation, permanent placement of an IHM in
      symptomatic heart failure patients is technically feasible. Further investigation
      is warranted to evaluate the use of the continuous hemodynamic data in management
      of heart failure patients.

PMID- 16105000
TI  - Invasive optimization of cardiac resynchronization therapy: role of sequential
      biventricular and left ventricular pacing.
AB  - BACKGROUND: Aim of this invasive study was to characterize and quantify changes
      in left ventricular (LV) systolic function due to sequential biventricular pacing
      (BV) as compared to right atrial triggered simultaneous BV (BV(0)), LV, and right
      ventricular (RV) pacing in patients with congestive heart failure (CHF). METHODS:
      In 22 CHF patients, all in sinus rhythm, temporary multisite pacing was performed
      prior to implantation of a permanent system. LV systolic function was evaluated
      invasively by the maximum rate of LV pressure increase (dP/dt(max)). Sequential
      BV pacing was performed with preactivation of either ventricle at 20-80 ms.
      RESULTS: In comparison to RV pacing, LV and BV(0) pacing increased dP/dt(max) by
      33.9 +/- 19.3% and 34.0 +/- 22.6%, respectively (P < 0.001). In 9 patients,
      optimized sequential BV pacing further improved dP/dt(max) by 8.5 +/- 4.8%
      compared to BV(0) (range 3.3-17.1, P < 0.05). In 10 patients exhibiting a PR
      interval < or =200 ms, LV pacing was either superior (n = 6) or equal to BV(0)
      pacing (n = 4). In these 10 patients, LV pacing yielded a 7.4 +/- 8.0% higher
      dP/dt(max) than BV(0) pacing (P < 0.05). CONCLUSIONS: Using sequential BV pacing,
      generally with LV preactivation, moderate improvements in LV systolic function
      can be achieved in selected patients. Baseline PR interval may aid in the
      selection of the optimum cardiac resynchronization therapy (CRT) mode, favoring
      LV pacing in patients with a PR interval < or =200 ms.

PMID- 16105001
TI  - Clinical and quality of life comparison of accelerometer, piezoelectric crystal,
      and blended sensors in DDDR-paced patients with sinus node dysfunction in the
      mode selection trial (MOST).
AB  - INTRODUCTION: Permanent pacemakers are capable of increasing heart rate in
      response to physical activity by a variety of sensors including accelerometers,
      piezoelectric crystals, or blended sensors. The impact of these different
      physiologic sensors on cardiovascular events and quality of life is not known.
      METHODS: Of 2,010 patients randomized in the Mode Selection Trial, 1,245 patients
      were selected with the most commonly used pacemakers with these three sensors.
      Clinical characteristics and quality of life were compared between groups at
      baseline, 3 months, and then yearly. RESULTS: There were 449 patients with an
      accelerometer sensor device, 682 with a piezoelectric sensor, and 114 with a
      blended sensor. The groups were similar in terms of age (mean 74 years), gender,
      and cardiac risk factors but differences existed in weight, heart rate, mitral
      regurgitation, revascularization history, and drug therapy. The median
      ventricular pacing frequency was 80% (25th, 75th percentiles 42, 97). After a
      median follow-up of 33.1 months, the risk of death, heart failure
      hospitalization, atrial fibrillation, and the combined endpoint of mortality and
      stroke was not significantly different between the sensor types, after adjustment
      for baseline differences. Quality of life analyses demonstrated that patients
      with blended sensors had significantly worse (P < 0.01) physical function than
      did patients with the other two sensor systems. Moreover, patients receiving
      blended sensors had the poorest absolute scores, without reaching statistical
      significance, on 9 of 13 quality of life measures after adjusting for differences
      in the groups. CONCLUSION: We found no significant differences among the three
      most utilized sensors in clinical endpoints. Those patients who received blended
      sensors had worse physical function quality of life scores. However, clinical
      selection of the most sophisticated sensor for the most ill patients cannot be
      excluded as an explanation of these results.

PMID- 16105002
TI  - The effect of anodal stimulation on V-V timing at varying V-V intervals.
AB  - We studied the effect of anodal capture at the ring electrode of the right
      ventricular (RV) lead on interventricular (V-V) timing during biventricular (BiV)
      pacing, in which left ventricular (LV) pacing was preceding RV pacing. The V-V
      interval was programmed from 80 to 4 ms (LV first) in the LV unipolar (LV tip-
      generator can) followed by the LV tip-RV ring pacing configuration. In the LV
      unipolar configuration, V-V programming leads to a continuous change in
      morphology of the QRS complex according to a change in collision of both
      activation fronts. When using the LV tip-RV ring configuration with anodal
      capture at the RV ring electrode no change in QRS morphology was recorded varying
      the V-V interval from 80 to 60 and 40 ms. However, at V-V intervals between 20
      and 4 ms a change in morphology of the QRS complex was recorded, which was due to
      additional cathodal stimulation of the RV tip electrode during RV stimulation.

PMID- 16105003
TI  - Temporal relationship of implantable cardioverter defibrillator discharges and
      environmental physical activity.
AB  - BACKGROUND: Studies by our group have shown an inverse relationship between
      sudden death and cardiac rhythm disturbances and environmental levels of
      geomagnetic activity (GMA). The aim of this study was to use the precise data
      provided by automatic implantable cardioverter defibrillators (ICDs) regarding
      the onset of ventricular fibrillation and ventricular tachycardia to link these
      events to GMA level. PATIENTS AND METHODS: The study group included 25 patients
      (22 men; 22 with ischemic cardiomyopathy) aged 28-81 years in whom an ICD had
      been implanted between 1995 and 2004. Patients were referred to the cardiac
      intensive care unit after each event that induced one or more discharges. The
      number of events and the day on which they occurred were recorded. Data on GMA
      and other cosmophysical parameters were obtained from the U.S. National
      Geophysical and Space Service Centers and the Russian Academy of Sciences. GMA
      levels, graded from I (quiet) to IV (stormy) in the middle latitutes, were
      recorded for 1974-2003 (10,954 days) and for each day on which an ICD discharge
      occurred. RESULTS: A total of 402 discharges were recorded on 137 days during the
      study period. Forty-six percent of the discharges took place on days of GMA I,
      compared with 38% - II, 13% - III, and 3% - IV. The daily distribution of GMA was
      as follows: level I - 35.2%, II - 37.3%, III - 21.86%, IV - 5.61%. Comparison of
      ICD discharge days and actual multiyear levels of GMA (in percent) yielded a
      ratio of 1.326 for GMA I, 1.076 - II, 0.459 - III, 0.390 - IV. There was a
      significant inverse correlation between GMA level and number of discharges (r =
      0.97, P = 0.03) and days of treatment (r =-0.96, P = 0.039), and a significant
      difference between ICD discharges on days of GMA I and GMA II-IV (chi(2)= 5.05, P
      = 0.02). CONCLUSION: The higher number of ICD discharges on days of lowest GMA
      may be explained by a possible antiarrhythmic effect of GMA. Environmental
      arrhythmogenic factors that act inversely to GMA may be activated at times of low
      GMA.

PMID- 16105005
TI  - Far-field R-wave reduction with a novel lead design: experimental and human
      results.
AB  - INTRODUCTION: The purpose of this study was to examine a bipolar screw-in lead
      (NL), specially designed to reduce unwanted far-field R-wave (FFRW) signal
      detection in an acute human setting. The results were compared with animal
      experiments. METHODS: The newly designed lead with a center-to-center distance
      between the anode and cathode electrodes of 3.23 mm, corresponding to an inter
      electrode spacing of 1.1 mm was implanted in nine canines with a follow-up of 6
      months. Sensing of P waves, FFRW signals, pacing threshold, and impedance was
      measured at regular intervals. As a result of the positive outcome with the
      animal study, an acute human experiment was performed. In patients scheduled for
      conventional dual chamber pacemaker implantation, the NL was compared to a
      Tendril Model 1388T bipolar screw-in lead (St. Jude Medical, CRMD, Sylmar, CA).
      RESULTS: Utilizing a tip-to-ring distance of 1.1 mm, the optimum P wave to FFRW
      ratio was found in animal experiments. In the acute human tests in 15 patients,
      the mean P-wave voltage of the 1388T lead of 3.30 +/- 1.54 mV was slightly larger
      than that of the NL, at 2.55 +/- 1.11 mV, but did not differ significantly (P =
      0.13). The FFRW voltage of the 1388T lead was 0.62 +/- 0.37 mV and was
      significantly greater from that of the NL, at 0.10 +/- 0.08 mV (P < 0.0001).
      Pacing thresholds and pacing impedances were comparable. CONCLUSION: Animal
      testing results were reproducible in the acute human test setting. The lead
      reduced the paced FFRW signal amplitudes significantly, allowing for high atrial
      sensitivity settings but without sensing the FFRW. A robust P-wave signal could
      be retained.

PMID- 16105006
TI  - The impact of povidone-iodine pocket irrigation use on pacemaker and
      defibrillator infections.
AB  - BACKGROUND: Infection is a devastating complication of permanent pacemakers (PMs)
      implantable cardioverter defibrillators (ICDs). Many implanting physicians
      commonly use povidone-iodine solution to irrigate the device pocket before
      implanting the device. We sought to assess if such a measure would alter the rate
      of infection. METHODS: A total of 2,564 consecutive patients who received
      implantable PM or ICD devices between 1994 and 2002 were studied. Povidone-iodine
      was used for pocket irrigation in 53% and saline in 47%. A total of 18 (0.7%)
      patients developed pocket infections with 0.7% (10/1,359) in povidone-iodine
      (group I) and 0.6% (8/1,205) in saline (group II) pocket irrigation (p = ns).
      Groups I and II were studied for various clinical and demographic variables
      described in the results section. RESULTS: There was no statistical difference in
      the baseline demographic and clinical characteristics between groups I and II,
      respectively. ICDs were most frequently infected than PMs (56% vs 44%). Most
      (83%) of the devices were dual chamber. Reopening of the pocket for either lead
      or generator replacement had a higher incidence of infection than new implants
      (61% vs 39%). There was no difference in the use of preimplantation antibiotic
      prophylaxis. Late (61%) and deep pocket infections (78%) were more common than
      early (39%) and superficial infections (22%). Blood cultures were positive in 67%
      and Staphylococcus aureus was the common most pathogen (50%). The mean duration
      of antibiotics use after the diagnosis of device infection was 35 +/- 23 days
      with 72% requiring device explantation. The device was reimplanted on the
      contralateral side in 56% cases. One patient in each group died due to device
      infection and related complications. No significant allergy to iodine was seen in
      either group. CONCLUSION: Povidone-iodine irrigation of the subcutaneous pocket
      did not alter the rates of pocket infection after pacemaker/defibrillator
      implantation.

PMID- 16105007
TI  - Incidence of complications in patients with implantable
      cardioverter/defibrillator who receive additional transvenous pace/sense leads.
AB  - BACKGROUND: Implantation of an additional pace/sense (P/S) lead is commonly used
      in patients with implantable cardioverter/defibrillators (ICDs) to overcome P/S
      defects of integrated defibrillation leads (HV-P/S leads). No information is
      available about the clinical outcome and the incidence of complications in these
      patients. METHODS: Retrospective analysis was performed in 151 patients (125
      male, age 54.9 +/- 13.6 years, LVEF 48.1 +/- 17.8%, CAD in 86 [57%], DCM in 24
      [16%], ARVCM in 11 [7%]) who received an additional P/S lead between 1990 and
      2002 (54 patients with abdominal and 97 patients with pectoral ICD system).
      Statistical analysis was done using Kaplan-Meier survival curves. RESULTS: The
      average follow-up (FU) after implantation of the additional P/S lead was 43 +/-
      27 months. In total 117 patients [77.5%] remain implanted; 22 patients died due
      to cardiac-related reasons. After a FU of 23 +/- 23 months, 43 patients [28.5%]
      experienced lead-related problems after implantation of the additional P/S lead:
      oversensing in 23 [53.5%], insulation defect in 3 [7.0%], fracture in 1 [2.3%],
      system infection in 4 [9.3%], and defect of the HV-P/S lead in 6 [14.0%]
      patients. The event-free cumulative survival of the additional P/S lead after 1,
      2, and 5 years was 87.0%, 79.8%, and 59.4%, respectively (for pectoral leads:
      89.6%, 82.0%, and 60.0%, respectively). CONCLUSIONS: Implantation of an
      additional P/S lead in case of failure of an HV-P/S lead is safe. However, it is
      associated with a substantial rate of complications during FU. Therefore,
      extraction of damaged defibrillation leads instead of implantation of P/S leads
      should be favored.

PMID- 16105008
TI  - Understanding atrial symptom reports: objective versus subjective predictors.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is
      associated with a variety of symptoms such as dizziness, palpitations, shortness
      of breath, and other signs of heart failure, which in turn impact quality of life
      (QOL). Implantable cardioverter defibrillators with atrial therapies (ICDs-ATs)
      have been shown to reduce AF symptoms and improve QOL in select AF samples.
      METHOD: This study examined the strength of relationships between objective
      (device-detected AF events) versus subjective (emotional symptoms) data and AF
      symptoms (number) reported as part of the Patient Atrial Shock Survey of
      Acceptance and Tolerance Study (N = 96, 72% men, M age = 65, SD = 12). Depression
      and anxiety were assessed via the Center for Epidemiological Studies--Depression
      Scale and the-State Trait Anxiety Inventory. AF disease burden was measured via a
      number of device-detected AF episodes and the Atrial Tachyarrhythmia Symptom
      Severity Scale. RESULTS: Hierarchical multiple regression analysis indicated that
      negative emotions accounted for a significant 13.2% of unique variance in AF
      symptom score (F change (1, 54) = 9.625, P = 0.003). On the other hand, the
      number of device-detected AF episodes accounted for non-significant 8.2% of
      unique variance in the AF symptom score (P = 0.167). The full model explained
      25.7% of the variance in AF symptom score (F(6, 54) = 3.110, P = 0.011).
      Specifically, greater number of treated AF episodes (beta= 0.251, P = 0.043) and
      higher levels of negative emotions (beta= 0.369, P = 0.003) predicted greater
      number of reported AF symptoms. CONCLUSION: Therefore, psychological distress may
      be a significant confounding factor affecting patient's report of AF symptoms
      rather than the actual experience of recurrent AF episodes.

PMID- 16105009
TI  - Reentry within the cavotricuspid isthmus: an isthmus dependent circuit.
AB  - BACKGROUND: We describe a new cavotricuspid isthmus (CTI) circuit. METHODS: This
      study includes 8 patients referred for atrial flutter (AFL) ablation whose
      tachycardia circuit was confined to the septal CTI and the os of the coronary
      sinus (CS(OS)) region. Entrainment mapping was performed within the CTI, CS(OS),
      and other right atrial annular sites (tricuspid annulus (TA)). Electroanatomic
      mapping was available in 2 patients. RESULTS: Sustained AFL occurred in all
      patients with mean tachycardia cycle length (TCL) of 318 +/- 54 (276 - 420) ms.
      During tachycardia, fractionated or double potentials were recorded at either the
      septal CTI and/or the region of CS(OS) in all, and concealed entrainment with
      post-pacing interval (PPI)--TCL < or = 25 ms occurred in this area; but manifest
      entrainment with PPI > TCL was demonstrated from the anteroinferior CTI and other
      annular sites in 7/8 patients. In one, tachycardia continued with conduction
      block at the anteroinferior CTI during ablation. Up to three different right
      atrial activation patterns (identical TCL) were observed. The tachycardia showed
      a counterclockwise (CCW) pattern in 6, a clockwise pattern in 2, and simultaneous
      activation of both low lateral right atrium and septum in 5. Electroanatomic
      mapping was available in 2, showing an early area arising from the septal CTI in
      1, and a CCW activation sequence along the TA in another. Radiofrequency
      application to the septal CTI terminated tachycardia in 4, and tachycardia no
      longer inducible in all. CONCLUSIONS: We describe a tachycardia circuit confined
      to the septal CTI/CS(OS) region, and hypothesize that this circuit involves slow
      conduction within the CTI and around the CS(OS), which acts as a central
      obstacle.

PMID- 16105010
TI  - Continuous positive airway pressure treatment improves the QT rate dependence
      adaptation of obstructive sleep apnea patients.
AB  - BACKGROUND: QT rate dependence is one of the major properties of ventricular
      repolarization, with its circadian and autonomic modulations. The alteration of
      cardiac autonomic tone occurring in obstructive sleep apnea syndrome (OSAS)
      patients could explain the altered rate-dependent adaptation of the myocardial
      repolarization. Thus, we postulated that dynamic alterations in QT interval
      adaptation could be ameliorated in OSAS patients under continuous positive airway
      pressure (CPAP) treatment. To assess ventricular repolarization features in
      patients with OSAS, we compared QT parameters and their dynamicities along RR
      intervals from 24-hour ECG. METHODS: The study groups consisted of 38 consecutive
      OSAS patients and 38 healthy age-matched subjects. The syndrome was confirmed for
      OSAS patients according to standard polysomnographic criteria (apnea plus
      hypopnea index: 56.9 +/- 28.4/h). A second polysomnography synchronized with 24
      hour ECG Holter and realized under efficient CPAP therapy confirmed the control
      of sleep-related breathing disorder. RESULTS: QT length related to heart rate was
      found significantly altered in patients with OSAS compared with controls
      (QTend/RR slope: -0.126 +/- 0.031 vs -0.173 +/- 0.038; P < 0.01). This flattened
      relationship was significantly improved with the treatment of the OSAS (-0.151 +/
      0.051; P < 0.01 vs pretreatment status). There was no significant impact of CPAP
      therapy on ventricular ectopic activity as well as on static repolarization
      parameters (QT, RT, QTc, RTc) measured separately over daytime and nighttime.
      CONCLUSIONS: The prognostic implications of such findings and the protective role
      of CPAP treatment to prevent sudden cardiac death in OSAS need to be evaluated.

PMID- 16105011
TI  - Multichannel data acquisition system for mapping the electrical activity of the
      heart.
AB  - BACKGROUND: Details of the electrical conduction pattern of the heart are
      revealed to the electrophysiologist when multichannel data are used for
      activation mapping. Commercial electronic systems are available for simultaneous
      acquisition of many surface electrograms; however, the cost of these systems may
      be prohibitive and they can be mostly inflexible for adaptation to other research
      projects. Furthermore, the hardware and software design is often proprietary. In
      this article we describe the in-house design and implementation of a 320
      multichannel acquisition system for animal electrophysiologic research. METHOD
      AND RESULTS: Several modules comprise this system. The multichannel data are
      first preprocessed by amplification, filtering, and analog multiplexing. An
      algorithm for automatic adjustment of signal gains is implemented to maximize the
      voltage resolution and minimize noise pickup. Signals are then digitized, and
      sequenced to order the multichannel data and to add markers required for
      analysis. The digital data are streamed to archival storage media. Additionally,
      the electrocardiogram (ECG), blood pressure, and stimulus channel signals are
      stored simultaneously. Selected signals are then displayed in real-time for
      measurement and analysis and as a check of the system integrity. Examples of
      multielectrode arrays and surface recordings are provided. Costs for building
      such a system are estimated. CONCLUSIONS: Multichannel data acquisition systems
      that are designed and constructed in-house have several advantages over turnkey
      commercial systems, including the potential for considerable cost savings,
      flexibility in acquiring data, and the ability to subsequently add additional
      components.

PMID- 16105012
TI  - Impact of duration of cryothermal application on clinical efficacy of pulmonary
      vein isolation using transvenous cryoablation.
AB  - BACKGROUND: Recent studies have demonstrated that transvenous cryoablation is a
      safe and feasible method for pulmonary vein (PV) isolation for treatment of
      atrial fibrillation (AF). However, this technique is limited by a much longer
      ablation time than conventional radiofrequency ablation. The aim of this study
      was to determine the effect of duration of cryoablation application with double
      freeze-thaw cycles on clinical efficacy for PV isolation for treatment of AF.
      MATERIALS AND RESULTS: We compared the clinical efficacy and procedural time of
      cryoablation (CryoCorTM, San Diego, CA, USA) for segmental PV isolation in 30
      patients (mean age 51 +/- 13, 20 men) with paroxysmal AF using either double 5
      minute (n = 15) or double 2.5-minute (n = 15) freeze-thaw cycle delivered with a
      10 F deflectable transvenous catheter. Clinical recurrence of AF and the
      occurrence of PV stenosis as determined by computer tomography of the thorax were
      performed at 3- and 12-month follow-up. Acute successful electrical isolation of
      PV was achieved with cryoablation in 96 of 98 (98%) targeted PVs in 30 patients
      (mean: 3.2 +/- 0.8 PVs per patient). There were no significant differences
      between the baseline characteristics, the number of PV isolated per patient, the
      total number and percentage of effective cryoablation and the acute clinical
      efficacy between using double 5-minute and double 2.5-minute freezes (P > 0.05).
      However, the fluoroscopy time (107 +/- 43 vs 138 +/- 113 minutes, P = 0.06) and
      the procedural time (360 +/- 113 vs 510 +/- 115 minutes, P = 0.01) of using
      double 2.5-minute freezes was reduced by approximately 30% compared with double 5
      minute freezes. At a mean of 20 +/- 8 month follow-up, there was no significant
      difference in the chronic clinical efficacy of cryoablation in terms of freedom
      from AF in the absence of antiarrhythmic drug therapy between using double 5
      minute (6/15, 40%) and double 2.5-minute freezes (7/15, 46%, P = 0.98).
      CONCLUSION: As compared with double 5-minute freeze, the use of a shorter double
      2.5-minute freeze protocol significantly reduces the procedural time without
      affecting the acute and long-term clinical efficacy of cryoablation to isolate PV
      for treatment of AF.

PMID- 16105013
TI  - Effects of intravenous magnesium in a prolonged QT interval model of polymorphic
      ventricular tachycardia focus on transmural ventricular repolarization.
AB  - BACKGROUND: This study was performed to clarify the antiarrhythmic effects of
      magnesium sulfate (Mg(++)) in a prolonged QT interval canine model of polymorphic
      ventricular tachyarrhythmia (VTA). METHODS: In six experiments in a canine model
      of prolonged QT by anthopleurin-A, Mg(++) was administered in boluses of 0.2
      mL/kg during repetitive episodes of self-terminating polymorphic VTA or frequent
      premature ventricular complexes (PVCs). The distribution of ventricular
      repolarization across the left ventricular(LV) wall and dispersion of transmural
      repolarization were analyzed before, and 30 and 120 seconds after Mg(++)
      administration, during ventricular pacing at 100 bpm. Transmural unipolar
      electrograms were recorded from multipolar needle electrodes, and local
      activation-recovery intervals (ARI) were measured. RESULTS: Mg(++) rapidly
      eliminated self-terminating polymorphic VTA and all isolated PVCs. During
      ventricular pacing at 100 bpm, Mg(++) caused modest shortening of ARI at all
      recording sites. Since the magnitude of ARI shortening was greater at mid
      myocardial sites than at other ventricular sites, mean transmural ARI dispersion
      decreased from 80 +/- 22 to 45 +/- 18 ms within 30 seconds after Mg(++)
      injection. However, this effect was transient, and, at 120 seconds after Mg(++)
      administration, ARI had increased all sites and transmural ARI dispersion
      lengthened to 65 +/- 18 ms. Besides suppression of triggered premature activity,
      homogenization of transmural ventricular repolarization was associated with the
      antiarrhythmic effects of intravenous Mg(++) in this model. CONCLUSION: Since
      these effects were transient, a continuous intravenous infusion of Mg(++) is
      preferred to prevent recurrences of VTA.

PMID- 16105014
TI  - Unusual QRS morphology on ECG: a rare condition and an interesting response to
      pacing.
AB  - We present the interesting case of a young man with borderline wide QRS complexes
      noted on electrocardiogram (ECG). The diagnosis of an unusual form of
      preexcitation was reached using observations from intracardiac tracings at
      electrophysiology study. Atrial pacing consistently resulted in further widening
      of the first conducted QRS complex, and the physiology underlying this unusual
      finding is explored.

PMID- 16105015
TI  - Bachmann's bundle: does it play a role in atrial fibrillation?
AB  - BACKGROUND: Cardiac anatomists have known the presence of a group of specialized
      fibers connecting the right and left atrium for years. However, only recently
      have clinical cardiologists come to recognize the potential importance of this
      specialized conduction system. Anatomical and microscopic studies have shown that
      the Bachmann's bundle (BB) represents a distinct structure similar to the atrio
      ventricular node and the His-Purkinje conduction system but without any
      insulating tissue. RESULTS: BB cells have specialized electrophysiological
      properties like supernormal excitability and faster longitudinal conduction that
      can facilitate more rapid impulse transmission compared to the normal atrial
      tissue. Experimental blockage of this pathway causes prolongation and widening of
      the P wave, which is associated with an increased incidence of atrial
      fibrillation. Atrial pacing is effective in reducing the incidence of atrial
      fibrillation by preventing bradycardia, synchronizing the atria, limiting
      anisotropy and reducing the dispersion of refractoriness. Various animal and
      human studies have shown pacing near the right atrial insertion of BB to have a
      beneficial effect in patients with interatrial conduction delay and atrial
      tachyarrhythmias. This mode of atrial septal pacing is convenient, safe,
      reliable, and clinically as effective as multisite pacing. CONCLUSION: This
      article is an effort to define the special properties of BB and its possible role
      in prevention of atrial fibrillation by permanent pacemakers.

PMID- 16105016
TI  - Unique Dacron reaction to an implanted pulse generator.

PMID- 16105017
TI  - Angioplasty facilitated permanent pacing in de novo superior vena cava
      obstruction.
AB  - The finding of complete occlusion of the superior venal cava during the
      performance of cardiac pacing is rare. We report a case where performance of
      angioplasty aided the successful completion of permanent pacemaker implantation.

PMID- 16105018
TI  - Arrhythmic storm responsive to quinidine in a patient with Brugada syndrome and
      vasovagal syncope.
AB  - A 37-year-old man with Brugada syndrome (BrS) and arrhythmic storm is described.
      One month after implantation of a cardioverter-defibrillator he presented with
      recurrent appropriate shocks for spontaneous ventricular fibrillation (VF).
      Because of this arrhythmic storm, quinidine therapy was initiated with total
      suppression of all spontaneous arrhythmias. He had remained free of arrhythmias
      for 22 months since quinidine initiation. Two episodes of VF occurred after the
      patient stopped taking the medication. The patient resumed quinidine and has been
      free of VF for the last 3 months. This response to quinidine in a patient with
      symptomatic BrS supports its role in the prophylaxis of arrhythmic events in BrS.

PMID- 16105019
TI  - Acquired arteriovenous fistula and chronic occlusion of the left anterior
      descending coronary artery in a patient with previous ablation of a left-sided
      accessory pathway.
AB  - Endocardial catheter ablation of accessory pathways is now considered as therapy
      of first choice in symptomatic patients. Success rates depend on the location of
      the accessory pathway itself and the operators experience in catheter ablation
      procedures. In patients with a left-sided pathway the retrograde transaortic
      catheter approach is used routinely in most centers. Besides occasional injuries
      of the vessels used for catheter placement and perforation of the cardiac
      chambers, there have been only a few case reports in the literature reporting
      rare procedure-specific complications such as catheter entrapment within the
      mitral valve apparatus and occlusion of the left circumflex coronary artery. We
      report a case of primary successful endocardial catheter ablation of a left
      lateral accessory pathway in a patient with normal coronary arteries at that
      time. Many years later progressive deterioration of systolic left ventricular
      function was observed. Coronary angiography revealed occlusion of LAD next to a
      arteriovenous (AV) fistula between the LAD and the anterior right ventricle.
      Endocardial catheter ablation was the only known cardiac manipulation in this
      patient raising the possibility that unintended catheter manipulations within the
      LAD had led to this rare and severe complication.

PMID- 16105020
TI  - Atypical proarrhythmia with dofetilide: monomorphic VT and exercise-induced
      torsade de pointes.
AB  - Proarrhythmia with dofetilide has most typically taken the form of torsade de
      pointes (TdP) and generally occurs early with therapy, such that in-hospital
      initiation of dofetilide with 3 days of continuous electrocardiogram monitoring
      is recommended. This article reports two unusual variants of ventricular
      proarrhythmia with dofetilide: (1) nonsustained runs of monomorphic ventricular
      tachycardia shortly after taking the first dose of dofetilide, confirmed by
      rechallenge; and (2) TdP that followed the development of isolated ventricular
      premature beats during an exercise test in a patient with neither excessive QT
      prolongation on dofetilide nor any ectopy whatsoever during in-hospital
      telemetric monitoring but with significant QT interval prolongation after the
      postectopic pause. These cases demonstrate that clinicians must be alert to the
      appearance of proarrhythmia with dofetilide at times other than early during drug
      initiation if the electrophysiological milieu is altered during nonhospital
      activity and/or of a pattern other than TdP.

PMID- 16105022
TI  - Unraveling the racial disparities associated with kidney disease.
AB  - In the United States, chronic kidney disease (CKD), and in particular end-stage
      renal disease (ESRD), represent a growing problem. Many other countries also have
      an increasing number of ESRD cases. Racial/ethnic disparities have been
      documented globally in the prevalence, incidence, and treatment of CKD, most
      extensively in the United States, but also in the United Kingdom, Australia, and
      New Zealand, among others. In many circumstances, these disparities are of a
      negative nature, that is, certain racial/ethnic groups fare worse than their
      white counterparts with respect to the treatment or outcome of CKD. However, in a
      few circumstances, they are of a positive nature, such as the survival advantage
      seen in minorities with ESRD compared with whites. The reasons for racial
      disparities in the prevalence, incidence, and treatment of CKD are not fully
      understood, although they are explained partly by coexisting medical conditions
      and modifiable risk factors, such as socioeconomic, lifestyle, and cultural. It
      is likely, however, that the complete picture incorporates a complex interaction
      between these sociocultural, genetic, and environmental factors. In a global
      society that prides itself on a high level of sensitivity and equality, there is
      an ethical and moral imperative to address the continuing racial/ethnic
      disparities in CKD and many of the factors underlying this epidemic. We review
      data highlighting the racial/ethnic disparities that exist in the incidence and
      treatment of CKD, with particular emphasis on ESRD. A better understanding of
      both the negative and positive racial/ethnic disparities may yield important
      insights, which can inform future research strategies and improve health outcomes
      for all patients afflicted with CKD.

PMID- 16105024
TI  - Aprt/Opn double knockout mice: osteopontin is a modifier of kidney stone disease
      severity.
AB  - BACKGROUND: Osteopontin (OPN) is reported to have two distinct functions in
      kidney disease: Promotion of inflammation at sites of tissue injury, and
      inhibition of calcium oxalate monohydrate stone formation. However, many of the
      studies supporting these functions were carried out in animal models of acute
      renal injury or in cultured cells; thus, the role of OPN in chronic renal disease
      is not well defined. We examined the role of OPN in adenine
      phosphoribosyltransferase (Aprt) knockout mice, in which inflammation and
      formation of 2,8-dihydroxyadenine (DHA) kidney stones are prominent features, by
      generating Aprt/Opn double knockout mice. METHODS: We characterized the
      phenotypes of six- and 12-week-old Aprt-/- Opn-/-, Aprt-/- Opn+/+, Aprt+/+ Opn-/
      , and Aprt+/+ Opn+/+ male and female mice using biochemical, histologic,
      immunohistochemical, and in situ hybridization techniques. RESULTS: At 6 weeks of
      age, there was no difference in phenotype between double knockout and Aprt
      knockout mice. At 12 weeks, there was increased adenine and DHA excretion, renal
      crystal deposition, and inflammation in double knockout versus Aprt knockout male
      mice. Double knockout and Aprt knockout female mice at 12 weeks had less
      pathology than their male counterparts, but kidneys from double knockout females
      showed more inflammation compared with Aprt knockout females; both genotypes had
      similar levels of DHA crystal deposition. CONCLUSION: We conclude that (1) OPN is
      a major inhibitor of DHA crystal deposition and inflammation in male mice; and
      (2) OPN is a major modifier of the inflammatory response but not of crystal
      deposition in female mice. Thus, separate mechanisms appear responsible for the
      tissue changes seen in DKO males versus females.

PMID- 16105023
TI  - Obstructive nephropathy: insights from genetically engineered animals.
AB  - Congenital obstructive nephropathy is the primary cause for end-stage renal
      disease (ESRD) in children. An increasingly used animal model of obstructive
      nephropathy is unilateral ureteral obstruction (UUO). This model mimics, in an
      accelerated manner, the different stages of obstructive nephropathy leading to
      tubulointerstitial fibrosis: cellular infiltration, tubular proliferation and
      apoptosis, epithelial-mesenchymal transition (EMT), (myo)fibroblast accumulation,
      increased extracellular matrix (ECM) deposition, and tubular atrophy. During the
      last decade genetically modified animals are increasingly used to study the
      development of obstructive nephropathy. Although the use of these animals (mainly
      knockouts) has highlighted some pitfalls of this approach (compensation by
      closely related gene products, absence of temporal knockouts) it has brought
      important information about the role of specific gene-products in the
      pathogenesis of obstructive nephropathy. Besides confirming the important
      pathologic role for angiotensin II (Ang II) and transforming growth factor-beta
      (TGF-beta) in obstructive nephropathy, these animals have shown the complexity of
      the development of tubulointerstitial fibrosis involving a large number of
      closely functionally related molecules. More interestingly, the use of these
      animals has led to the discovery of unexpected and contradictory roles (both
      potentially pro- and antifibrotic) for Ang II, for ECM degrading enzymes matrix
      metalloproteinase 9 (MMP-9) and tissue plasminogen activators (PAs), for
      plasminogen activator inhibitor 1 (PAI-1), and for the adhesion molecule
      osteopontin (OPN) in obstructive nephropathy. Further use of these animals,
      especially in combination with pharmacologic tools, should help to better
      identify potential antifibrotic strategies in obstructive nephropathy.

PMID- 16105025
TI  - A comparative study of three kidney biomarker tests in autosomal-dominant
      polycystic kidney disease.
AB  - BACKGROUND: The relationship between the progress of tubular damage and renal
      insufficiency in autosomal-dominant polycystic kidney disease (ADPKD) is a
      subject of doubtless interest, and is the object of this present work. METHODS: A
      total of 92 adult ADPKD patients of both genders were studied, none of which
      presented end-stage renal disease (ESRD), and classified according to an
      ultrasound score based on kidney size and number of cysts. Urinary albumin and
      beta-N-acetylhexosaminidase (Hex) and its isoenzymes were determined, together
      with serum glutathione peroxidase, cystatin C, creatinine, and urea. RESULTS: A
      frequent elevation of the urinary Hex was found and an alteration of its
      isoenzymatic profile, with 31% of the normotensive patients with normoalbuminuria
      already presenting an increased proportion of Hex B isoenzyme. Keeping age
      constant, a partial significant correlation was found between the ultrasound
      score and the proportion of Hex B (r = 0.352, P < 0.05), but not with albuminuria
      or cystatin C. In 42 patients the different biochemical variables were again
      determined after 1 year, finding that in the 13 normotensive patients with
      normoalbuminuria there had been a significant decrease in the concentration of
      cystatin C (P < 0.05), and a significant increase in the urinary excretion of
      albumin and Hex B isoenzyme (P < 0.05). By the other hand, in the other 29
      patients with micro- or macroalbuminuria and hypertension, no significant
      differences were found. CONCLUSION: The results point toward an important
      participation of tubular damage in the pathogenesis of this disease. It may also
      be suggested that in normotensive and normoalbuminuric ADPKD patients, a gradual
      increase of glomerular filtration would be produced. After the start of
      hypertension and microalbuminuria, the glomerular filtration rate (GFR) would
      decrease progressively, although more slowly.

PMID- 16105026
TI  - Mutagenesis of the epithelial polarity gene, discs large 1, perturbs
      nephrogenesis in the developing mouse kidney.
AB  - BACKGROUND: During development of the permanent mammalian kidney (metanephros)
      several key epithelial events occur such as ureteric branching morphogenesis and
      nephrogenesis. One of the first stages of nephrogenesis involves the conversion
      of mesenchymal cells to epithelial cells, and thus the metanephros provides an
      excellent model to study epithelial polarization. The aim of this study was to
      investigate the role of the epithelial polarity gene, discs large 1 (dlg1),
      during development of the mouse kidney. METHODS: We utilized mice with a gene
      trap vector insertion within dlg1 (dlg(gt)) resulting in a truncated Dlg1
      protein, lacking the SH3, protein 4.1 and guanylate kinase-like (GUK) domains,
      fused to a LacZ reporter. These mice were used to analyze the expression of Dlg1
      during kidney development, the subcellular localization of Dlg1 in epithelial
      cells, and the ability of Dlg1 to bind to calmodulin-associated serine/threonine
      kinase (CASK). Metanephric organ culture was used to study branching
      morphogenesis and nephrogenesis in wild-type and dlg(gt) mutant mice. RESULTS:
      Dlg1 was expressed in ureteric and mesenchyme-derived epithelial cells during
      kidney development. Truncation of Dlg1 altered the normal basolateral
      localization of Dlg1 restricting it to the adherens junction. Due to the loss of
      the SH3 domain the binding capacity of Dlg1 to CASK was reduced. Nephrogenesis
      was altered in dlg(gt)/dlg(gt) metanephroi with a 30% decrease in nephron number.
      CONCLUSION: Our results indicate that the loss of the SH3, protein 4.1 and/or GUK
      domains of Dlg1 disrupt epithelial polarity and perturb nephrogenesis either as a
      secondary consequence to a defect in ureteric branching morphogenesis and/or
      delay in mesenchyme-to- epithelial transition.

PMID- 16105027
TI  - Segregation of urine calcium excretion in families ascertained for
      nephrolithiasis: evidence for a major gene.
AB  - BACKGROUND: The quantitative genetics of urine calcium excretion has not been
      established. It is a trait of interest because hypercalciuria is commonly found
      in subjects with nephrolithiasis. The aim of this study was to model the
      segregation of this trait in a sample of French-Canadian families ascertained
      through a stone former. METHODS: Major gene, polygenic, and mixed models were fit
      to 24-hour urine calcium excretion from 567 individuals in 221 nuclear families,
      while simultaneously taking into account gender, age at examination, body mass
      index (BMI), and the use of thiazide drugs. The nuclear families were extracted
      from 154 pedigrees, some of which were four generations, with at least two
      siblings with a history of calcium stones. RESULTS: All the proposed genetic
      models fit the data significantly better than the null model. The most
      parsimonious model was the mixed codominant/polygenic model but it was
      statistically indistinguishable from the single-gene codominant model. In both of
      these models the heritability attributable to the major gene was estimated to be
      0.58. CONCLUSION: Our results suggest that a major gene with a relatively large
      effect on variation in urine calcium excretion is segregating in French-Canadian
      families with stone formers. This implies that the power of quantitative trait
      segregation analysis of urine calcium excretion may be increased in these
      families, and results indicate that it should be feasible to genetically map the
      quantitative trait locus.

PMID- 16105028
TI  - MAPK/AP-1-dependent regulation of PAI-1 gene expression by TGF-beta in rat
      mesangial cells.
AB  - BACKGROUND: Receptor-regulated Smads and/or mitogen-activated protein kinases
      (MAPKs) are involved in transforming growth factor-beta (TGF-beta)-induced
      expression of various genes, including plasminogen activator inhibitor-1 (PAI-1).
      Because the sequence of the promoter region in rat PAI-1 gene differs from that
      in the human gene, we examined the mechanisms of TGF-beta-induced rat PAI-1
      expression in rat mesangial cells. METHODS: TGF-beta1-induced PAI-1 and c-fos
      mRNA expressions were determined by Northern blot analysis. Activation of MAPKs
      and Smad proteins was evaluated by an immunoblot analysis. DNA binding activities
      of nuclear protein were examined by using an electrophoretic mobility shift assay
      (EMSA). The activities of PAI-1 promoter were measured by a luciferase reporter
      assay. RESULTS: Extracellular-regulated kinase (ERK) and c-Jun NH-terminal kinase
      (JNK) phosphorylation, c-fos mRNA expression, and activator protein-1 (AP-1) DNA
      binding activity stimulated by TGF-beta1 were completely suppressed by the ERK
      kinase (MEK) inhibitors. EMSA and reporter analysis revealed that an AP-1-like
      sequence located in the proximal region of the rat PAI-1 promoter was the target
      for TGF-beta1, and the disruption of this AP-1-like sequence suppressed basal and
      TGF-beta1-induced promoter activation. TGF-beta1 also stimulated nuclear
      translocation of Smads and binding to palindromic Smad binding element (SBE)
      located in the rat PAI-1 promoter, without being affected by MEK inhibitor. Point
      mutation and deletion of palindromic SBE did not affect TGF-beta1-induced rat PAI
      1 promoter activity. Moreover, interferon-gamma (IFN-gamma) inhibited TGF-beta1
      induced PAI-1 expression through selectively suppressing the ERK-AP-1 pathway.
      CONCLUSION: These results suggest that the essential requirement of MAPK/AP-1
      activation for TGF-beta1-induced PAI-1 expression is unique to rat mesangial
      cells.

PMID- 16105029
TI  - High glucose transactivates the EGF receptor and up-regulates serum
      glucocorticoid kinase in the proximal tubule.
AB  - BACKGROUND: Serum glucocorticoid regulated kinase (SGK-1) is induced in the
      kidney in diabetes mellitus. However, its role in the proximal tubule is unclear.
      This study determined the expression and functional role of SGK-1 in PTCs in high
      glucose conditions. As the epidermal growth factor (EGF) receptor is activated by
      both EGF and other factors implicated in diabetic nephropathy, the relationship
      of SGK-1 with EGFR activity was assessed. METHODS: mRNA and protein expression of
      SGK-1 and mRNA expression of the sodium hydrogen exchanger NHE3 were measured in
      human PTCs exposed to 5 mmol/L (control) and 25 mmol/L (high) glucose. The
      effects of SGK-1 on cell growth, apoptosis, and progression through the cell
      cycle and NHE3 mRNA were examined following overexpression of SGK-1 in PTCs. The
      role of EGFR activation in observed changes was assessed by phospho-EGFR
      expression, and response to the EGFR blocker PKI166. SGK-1 expression was then
      assessed in vivo in a model of streptozotocin-induced diabetes mellitus type 2.
      RESULTS: A total of 25 mmol/L glucose and EGF (10 ng/mL) increased SGK-1 mRNA (P
      < 0.005 and P < 0.002, respectively) and protein (both P < 0.02) expression. High
      glucose and overexpression of SGK-1 increased NHE3 mRNA (P < 0.05) and EGFR
      phosphorylation (P < 0.01), which were reversed by PKI166. SGK-1 overexpression
      increased PTC growth (P < 0.0001), progression through the cell cycle (P <
      0.001), and increased NHE3 mRNA (P < 0.01), which were all reversed with PKI166.
      Overexpression of SGK-1 also protected against apoptosis induced in the PTCs (P <
      0.0001). Up-regulation of tubular SGK-1 mRNA in diabetes mellitus was confirmed
      in vivo. Oral treatment with PKI166 attenuated this increase by 51%. No EGF
      protein was detectable in PTCs, suggestive of phosphorylation of the EGFR by high
      glucose and downstream induction of SGK-1. CONCLUSION: The effects of high
      glucose on PTC proliferation, reduced apoptosis and increased NHE3 mRNA levels
      are mediated by EGFR-dependent up-regulation of SGK-1.

PMID- 16105030
TI  - Structure of non-(1-84) PTH fragments secreted by parathyroid glands in primary
      and secondary hyperparathyroidism.
AB  - BACKGROUND: Non-(1-84) parathyroid hormone (PTH) fragments are large circulating
      carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N)
      structure. hPTH (7-84), a synthetic surrogate, has been demonstrated to exert
      biologic effects in vivo and in vitro which are opposite to those of hPTH (1-34)
      on the PTH/PTHrP type I receptor through a C-PTH receptor. We wanted to determine
      the N structure of non-(1-84) PTH fragments. METHODS: Parathyroid cells isolated
      from glands obtained at surgery from three patients with primary
      hyperparathyroidism and three patients with secondary hyperparathyroidism were
      incubated with 35S-methionine to internally label their secretion products.
      Incubations were performed for 8 hours at the patient-ionized calcium
      concentration and in the presence of various protease inhibitors. The supernatant
      was fractionated by high-performance liquid chromatography (HPLC) and fractions
      were analyzed with PTH assays having (1 to 4) and (12 to 23) epitopes,
      respectively. The serum of each patient was similarly analyzed. Peaks of
      immunoreactivity identified were submitted to sequence analysis to recover the
      35S-methionine residues in positions 8 and 18. RESULTS: Three regions of interest
      were identified with PTH assays. They corresponded to non-(1-84) PTH fragments
      (further divided in regions 3 and 4), a peak of N-PTH migrating in front of hPTH
      (1-84) (region 2) and a peak of immunoreactivity corresponding to the elution
      position of hPTH (1-84) (region 1). The last corresponded to a single sequence
      starting at position 1. Region 2 gave similar results in all cases (a major
      signal starting at position 1) but also sometimes minor sequences starting at
      position 4 or 7. Regions 3 and 4 always identified a major sequence starting at
      positions 7 and minor sequences starting at positions 8, 10, and 15.
      Surprisingly, a major signal starting at position 1 was also present in region 3.
      The HPLC profile obtained from a given patient's parathyroid cells was
      qualitatively similar to the one obtained with his/her serum in each case.
      CONCLUSION: These results indicate that non-(1-84) PTH fragments are composed of
      a family of fragments which may be generated by specific or progressive cleavage
      at the N region. The longest fragment starts at position 4 and the shortest at
      position 15. A peptide starting at position 7 appears as the major component of
      non-(1-84) PTH fragments. The generation process is similar to the one described
      for smaller C-PTH fragments a number of years ago, suggesting a similar
      production mechanism and source for all C-PTH fragments.

PMID- 16105031
TI  - Uroguanylin and guanylin regulate transport of mouse cortical collecting duct
      independent of guanylate cyclase C.
AB  - BACKGROUND: Electrolyte and water homeostasis mostly depend on differentially
      regulated intestinal and renal transport. Guanylin and uroguanylin were proposed
      as first hormones linking intestinal with renal electrolyte and water transport,
      which is disturbed in pathophysiology. Guanylate cyclase C is the intestinal
      receptor for these peptides, but in guanylate cyclase C-deficient mice renal
      effects are retained. Unlike for the intestine the sites of renal actions and
      cellular mechanisms of guanylin peptides are still unclear. METHODS: After first
      data on proximal tubular effects in this study their effects are examined in
      detail in mouse cortical collecting duct (CCD). Effects of guanylin peptides on
      principal cells of isolated mouse CCD were studied by slow whole-cell patch-clamp
      analysis, reverse transcription-polymerase chain reaction (RT-PCR), and
      microfluorimetric measurements of intracellular Ca2+. RESULTS: Guanylin peptides
      depolarized or hyperpolarized principal cells. Whereas 8-Br-cyclic guanosine
      monophosphate (8-Br-cGMP) hyperpolarized, 8-Br-cyclic adenosine monophosphate (8
      Br-cAMP) depolarized principal cells. All effects of guanylin peptides were
      inhibited by Ba2+. Hyperpolarizations were blocked by clotrimazole or protein
      kinase G (PKG) inhibition, suggesting an involvement of basolateral Ca2+- and
      cGMP-dependent K+ channels. Effects remained in CCD isolated from guanylate
      cyclase C-deficient mice. Depolarizations were inhibited by arachidonic acid or
      inhibition of phospholipase A2 (PLA2), but not by protein kinase A (PKA)
      inhibition. Conclusion. These results suggest the existence of two signaling
      pathways for guanylin peptides in principal cells of mouse CCD. One pathway is
      cGMP- and PKG-dependent but not mediated by guanylate cyclase C, the second
      involves PLA2 and arachidonic acid. The first pathway most likely leads to an
      activation of the basolateral K+-conductance while the latter probably results in
      decreased activity of ROMK channels in the luminal membrane.

PMID- 16105032
TI  - Catalase deficiency renders remnant kidneys more susceptible to oxidant tissue
      injury and renal fibrosis in mice.
AB  - BACKGROUND: Catalase is one of the important antioxidant enzymes regulating the
      levels of intracellular hydrogen peroxide and hydroxyl radical. The effect of
      catalase deficiency on progressive renal fibrosis has not been fully elucidated.
      METHODS: Homozygous acatalasemic mutant mice (C3H/AnLCs(b)Cs(b)) and control wild
      type mice (C3H/AnLCs(a)Cs(a)) were subjected to 5/6 nephrectomy. The functional
      and morphological alterations of the remnant kidneys, including
      tubulointerstitial fibrosis, epithelial to mesenchymal transition (EMT),
      peroxidation, antioxidant enzyme activity, and gene expression of EMT-related
      molecules were compared between the two groups at 6, 12, and 18 weeks after 5/6
      nephrectomy. RESULTS: The 5/6 nephrectomy resulted in albuminuria, decreased
      renal function, and tubulointerstitial fibrosis with accumulation of type I and
      type IV collagens in the remnant kidneys of both mouse groups. However, the
      degree of these changes was significantly higher in acatalasemic mice after 5/6
      nephrectomy as compared with wild-type mice until week 18. EMT, a crucial
      phenotypic alteration of tubular epithelial cells, was observed in acatalasemic
      mice by electron microscopy and was associated with upregulation of EMT-related
      alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta1 (TGF
      beta1), connective tissue growth factor (CTGF), and fibroblast specific protein-1
      (FSP-1) gene expression. Significant increases in the tubulointerstitial
      deposition of lipid peroxidation products, including 4-hydroxy-2-nonenal and
      urinary excretion of 8-hydroxy-2'- deoxyguanosine were observed in the
      acatalasemic mice after 5/6 nephrectomy as compared with the wild-type mice.
      Glomerular sclerosis developed after tubulointerstitial injury in acatalasemic
      mice. The level of catalase activity remained low in the remnant kidneys of
      acatalasemic mice until week 18 without compensatory up-regulation of glutathione
      peroxidase or superoxide dismutase (SOD) activity. Finally, supplementation of a
      SOD mimetic tempol did not prevent peroxidation and tubulointerstitial fibrosis
      in the acatalasemic remnant kidneys. CONCLUSION: These findings indicate that
      acatalasemia exacerbates renal oxidant tissue injury and sensitizes remnant
      kidneys to EMT and progressive renal fibrosis. This study suggests a central role
      for catalase in the defense against oxidant-mediated renal fibrosis.

PMID- 16105033
TI  - Urothelial differentiation in chronically urine-deprived bladders of patients
      with end-stage renal disease.
AB  - BACKGROUND: It is unknown whether normal bladder voiding function, or soluble
      factors present in urine, contribute to the maturation and maintenance of the
      differentiated state of the uroepithelial cell lining of the lower urinary tract.
      METHODS: We used the urothelium of anuric patients on long-term hemodialysis,
      sampled at the time of renal transplantation, to investigate the expression of
      urothelial differentiation-associated antigens, including uroplakins (UPIa, UPIb,
      UPII, and UPIIIa), cytokeratin isotypes (CK7, CK8, CK13, CK14, CK17, CK18, and
      CK20), nuclear hormone receptors [peroxisome proliferators activated receptor
      gamma (PPAR-gamma) and retinoid X receptor-alpha (RXR-alpha)], and a cell cycle
      marker (Ki-67). To determine whether urinary metabolites of the arachidonic
      pathway could induce urothelial differentiation, cultured normal human urothelial
      (NHU) cells were treated with 15-deoxy-delta12, 14-prostaglandin J2 (15d-PGJ2)
      and prostaglandin J2 (PGJ2). The expression levels of the markers of
      differentiation, the uroplakins, were assessed by ribonuclease protection assay.
      Results. When compared in a blinded analysis against control normal urothelium,
      no significant changes were found in the expression or localization patterns of
      any of the antigens studied in the anuric patients. Furthermore, neither 15d-PGJ2
      nor PGJ2 were able to induce expression of the UPII gene in NHU cells, in
      contrast to cultures exposed to the pharmacologic PPAR-gamma agonist,
      troglitazone. Conclusion. These data provide prima facie evidence that exogenous
      urine-derived factors do not modulate the differentiation program in urothelium,
      suggesting that other urothelial- or serum-derived factors are likely to be
      involved. These findings are important in understanding post-developmental
      maturation and functional relationships in urologic tissues of the adult
      organism.

PMID- 16105034
TI  - Mycophenolate mofetil ameliorates nephropathy in the obese Zucker rat.
AB  - BACKGROUND: The obese Zucker rat has metabolic condition resembling type II
      diabetes, including hyperlipidemia, obesity, insulin resistance, and
      hyperglycemia. With advancing age, the obese Zucker rat develops
      glomerulosclerosis, proteinuria, and renal failure. Since immune cells play a
      central role in the development of chronic renal injury, we evaluated the
      potential benefit of mycophenolate mofetil (MMF), alone and in combination with
      angiotensin receptor type 1 blockade (ARB) in the obese Zucker rat. METHODS:
      Thirteen-week-old male obese Zucker rats (fa/fa) were randomly assigned to four
      experimental groups (five rats each) that received the following treatments for 3
      months: (1) losartan (100 mg/L in the drinking water), (2) MMF (20 mg/kg/day),
      (3) MMF and losartan, and (4) placebo. Lean Zucker rats (N = 5) were included as
      normal controls. Renal function, biochemical parameters, renal histology, and
      immunohistology were evaluated. RESULTS: The placebo-treated obese Zucker rats
      exhibited proteinuria and significant glomerular and tubulointerstitial injury in
      association with renal immune cell infiltration. Proteinuria, histologic damage,
      and renal immune cell infiltration were all reduced by MMF treatment alone or in
      combination with ARB. The improvement of proteinuria and structural damage was
      more pronounced in the group that received the combination of MMF and losartan.
      CONCLUSION: MMF treatment alone, and especially in combination with ARB, improves
      nephropathy in the obese Zucker rat.

PMID- 16105035
TI  - Expression of HIV-1 genes in podocytes alone can lead to the full spectrum of HIV
      1-associated nephropathy.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-1-associated nephropathy (HIVAN)
      is characterized by collapsing focal and segmental glomerulosclerosis (FSGS) and
      microcystic tubular dilatation. HIV-1 infection is also associated with other
      forms of nephropathy, including mesangial hyperplasia. Since HIV-1 gene products
      are detected in podocytes and other renal cells, it remains uncertain whether
      podocyte-restricted HIV-1 gene expression can account for the full spectrum of
      renal lesions involving nonpodocytes. METHODS: To define the role of podocyte
      restricted HIV-1 gene expression in the progression of HIVAN, we generated
      transgenic mice that express nonstructural HIV-1 genes selectively in podocytes.
      RESULTS: Four of the seven founder mice developed proteinuria and nephropathy. In
      a subsequently established transgenic line, reverse transcription-polymerase
      chain reaction (RT-PCR) analysis detected mRNAs for vif, vpr, nef, and spliced
      forms of tat and rev, but not vpu, in the kidney. In situ hybridization localized
      HIV-1 RNA to the podocyte. Transgenic mice on FVB/N genetic background exhibited
      cuboidal morphology of podocytes with reduced extension of primary and foot
      processes at 2 weeks of age. After 3 weeks of age, these mice developed massive
      and nonselective proteinuria with damage of podocytes and other glomerular cells
      and, after 4 weeks of age, collapsing FSGS and microcystic tubular dilatation. In
      marked contrast, transgenic mice with C57BL/6 genetic background showed either
      normal renal histology or only mild mesangial expansion without overt podocyte
      damage. CONCLUSION: The present study demonstrates that podocyte-restricted
      expression of HIV-1 gene products is sufficient for the development of collapsing
      glomerulosclerosis in the setting of susceptible genetic background.

PMID- 16105036
TI  - Characterization of the T-cell epitope that causes anti-GBM glomerulonephritis.
AB  - BACKGROUND: We have demonstrated that a single T-cell epitope pCol(28-40)
      (SQTTANPSCPEGT) alone, which is derived from NC1 domain of alpha3 chain of type
      IV collagen (Col4alpha3 NC1), can induce severe glomerulonephritis in Wistar
      Kyoto rats. This study further characterized this T-cell epitope. METHODS: A
      series of synthetic peptides derived from pCol (28-40) were tested in vivo and in
      vitro for their T-cell epitope activity and nephritogenicity. Major
      histocompatability complex (MHC) class II molecules in Wistar Kyoto rats were
      cloned, and MHC restriction of pCol(28-40) was determined. RESULTS: The T-cell
      epitope pCol(28-40) was restricted by rat MHC class II RT.1Bl. Ten amino acid
      residues (29 to 38) were mapped to be the minimum core of the T-cell epitope,
      which was capable of inducing the T-cell response and severe glomerulonephritis.
      Only three residues were identified as absolutely critical for the T-cell
      epitope: position 31 (T) was an anchor residue to the class II molecule, and
      positions 33 (N) and 34 (P) contributed to the specificity of the T-cell epitope.
      Thus, only substitution at those positions completely abrogated nephritogenicity
      of the T-cell epitope. Interestingly, pCol (28-40) also bound to human MHC class
      II human MHC class II molecule HLA-DRB*1501, which has been linked to human anti
      glomerular basement membrane (GBM) disease, suggesting that human homologue of
      pCol(28-40) could be a potential human T-cell epitope. CONCLUSION: Our study
      demonstrated that only few residues in the nephritogenic T-cell epitope pCol(28
      40) were critical. Our finding also revealed that pCol(28-40) is a potential
      nephritogenic T-cell epitope in Goodpasture's syndrome.

PMID- 16105037
TI  - Scanning ion conductance microscopy reveals how a functional renal epithelial
      monolayer maintains its integrity.
AB  - BACKGROUND: To function as a transport barrier a renal tubule epithelial
      monolayer needs to maintain its integrity when, sudden hypertonic stress causes
      cell shrinkage, new cells are added, or cells in the monolayer die. However, the
      mechanism used to achieve this is largely unknown. Scanning ion conductance
      microscopy (SICM) has been shown to be suitable for imaging the surface of live
      renal cells with high topographic resolution, and can be used to elucidate how a
      functional renal epithelial monolayer maintains its integrity. METHODS: SICM was
      used for high spatial resolution topographic imaging of Xenopuslaevis renal
      epithelial A6 cells cultured on membrane filter inserts. RESULTS: The SICM images
      of A6 cells showed that the epithelial monolayer maintains its integrity under
      hypertonic stress, and during cell division and death. Sequential SICM
      topographic images revealed detailed structural changes and their time course for
      these protective processes, which involve highly cooperative cell movement. Some
      "balloon-like" structures were observed at susceptible tight junction regions,
      which were proposed to help cell maintaining the monolayer permeability
      integrity. CONCLUSION: SICM is a powerful tool for research on living renal
      epithelial cells, and has been used to elucidate how a functional epithelial
      monolayer maintains its integrity. Using this technique we have observed that
      during hypertonic stress and regeneration, an organized sequence of events
      protect the loss of integrity of monolayer so that tight junctions and cell-cell
      contact are maintained and disruption to the function of whole monolayer is
      prevented.

PMID- 16105038
TI  - Fibroblast-specific protein 1 is a specific prognostic marker for renal survival
      in patients with IgAN.
AB  - BACKGROUND: There is little direct evidence that fibroblasts are involved in the
      progression of the renal interstitial fibrosis in human glomerulonephritis. With
      the availability of a new specific marker for fibroblasts, we determined the
      presence of fibroblasts in kidneys with IgA nephropathy (IgAN) and correlated
      their numbers with various clinical parameters. In particular, we also
      prospectively asked if the number of fibroblasts in the renal interstitium
      correlates with prognosis. METHODS: Cells positive for fibroblast-specific
      protein 1 (FSP1) were localized in renal biopsy specimens using
      immunohistochemistry with anti-FSP1 antibody. Clinical features were analyzed by
      one-way analysis of variance (ANOVA) with the Bonferroni correction. To assess
      the prognostic impact of the number of FSP1+ fibroblasts on renal survival in 142
      patients with normal serum creatinine, the relationship between covariates to
      renal survival were evaluated univariately using the log-rank test and
      multivariately using Cox proportional hazards. RESULTS: Fibroblasts identified by
      their expression of FSP1 accumulate in areas showing severe interstitial
      fibrosis. Some tubular epithelial cells undergoing epithelial-mesenchymal
      transition (EMT) in fibrotic areas also express FSP1. Numbers of FSP1+
      fibroblasts directly correlate with serum creatinine (r = 0.74, P < 0.0001) and
      inversely correlate with estimated creatinine clearance (r = -0.54, P < 0.0001),
      and by multivariate analysis, the clinical factors influencing renal survival are
      urinary protein excretion [> or = 1.0 g/day, relative risk (RR) = 4.20, P=
      0.032], hypertension (RR 5.85, P = 0.0027), and > or = 20 FSP1+ fibroblasts per
      high power field (HPF) (RR 7.39, P = 0.0015). Staining for FSP1+ fibroblasts is
      largely nonoverlapping with alpha-smooth muscle actin+ (alpha-SMA) cells in the
      interstitium. CONCLUSION: The target protein FSP1 identifies human fibroblasts
      and tubular epithelium undergoing EMT, and distinguishes them from the diaspora
      of alpha-SMA+ vascular smooth muscle cells. FSP1+ fibroblasts are critically
      related to the progression of IgAN; consequently, staining FSP1 in renal biopsy
      specimens provides a valuable histologic index of progression.

PMID- 16105039
TI  - Adrenomedullin reduces mesangial cell number and glomerular inflammation in
      experimental mesangioproliferative glomerulonephritis.
AB  - BACKGROUND: Adrenomedullin (ADM) is a vasodilator peptide that is abundantly
      expressed in the kidney. ADM has antiproliferative effects on glomerular
      mesangial cells (MC) in vitro. Whether or not treatment with ADM can reduce MC
      proliferation in vivo [i.e., in mesangioproliferative glomerulonephritis (GN)] is
      unknown. We tested the hypothesis that ADM substitution reduces MC proliferation
      in GN. METHODS: GN in rats was induced by injection of an anti-Thy-1.1 antibody.
      Rats received osmotic minipumps, which continuously delivered rat ADM (500
      ng/hour, N = 11), or vehicle (N = 13) from day 3 to day 6 after GN induction.
      Rats were sacrificed 6 days after induction of GN. On kidney sections, cells
      staining positive for proliferating cell nuclear antigen, mesangial cells,
      monocytes, and apoptotic cells were counted. Parameters of inflammation and
      fibrosis were measured in renal cortex and sieved glomeruli by real-time
      polymerase chain reaction (PCR). RESULTS: Systolic blood pressure, diuresis,
      albuminuria, creatinine clearance, microaneurysm formation, and mesangial matrix
      expansion were not influenced by ADM infusion. However, ADM treatment
      significantly reduced the number of MC, showed a tendency to reduce total
      glomerular cell proliferation, and significantly increased apoptosis. ADM-treated
      GN animals showed significantly less glomerular monocyte infiltration. ADM
      treatment normalized transforming growth factor (TGF)-beta1 mRNA expression and
      reduced monocyte chemoattractant protein-1 (MCP-1), osteopontin, plasminogen
      activator inhibitor-1 (PAI-1), collagen I, and collagen III mRNA expression
      significantly. CONCLUSION: Exogenous ADM infusion reduces MC number and
      glomerular monocyte infiltration in the state of mesangial proliferation during
      acute experimental mesangioproliferative GN. These findings indicate that ADM can
      influence the course of mesangioproliferative GN.

PMID- 16105040
TI  - Antigen presentation by dendritic cells in renal lymph nodes is linked to
      systemic and local injury to the kidney.
AB  - BACKGROUND: Dendritic cells (DCs) uniquely serve as conduits between innate and
      cognate arms of the immune system. The normal kidney contains an extensive
      population of interstitial DCs but their role in the pathogenesis of acute renal
      injury is not known. METHODS: Renal DCs were studied by flow cytometric analysis
      of collagenase-digested mouse kidneys, by immunohistochemistry, and by
      immunofluorescence microscopy. In vivo ingestion by DCs of intravenously
      administered fluorescein isothiocyanate (FITC)-dextran particles was examined. A
      model antigen system (presentation of ovalbumin-derived peptide to TCR transgenic
      CD4+ T-cells) was employed to examine the influence of systemic
      (lipopolysacchride injection) and localized (unilateral renal artery clipping)
      renal injury on DC-mediated T-cell activation in the renal lymph nodes (RLNs).
      RESULTS: Renal DCs were shown to constitute the predominant source of T-cell
      stimulatory capacity within the kidney, and to avidly ingest both filtered and
      non-filtered particles. Lipopolysaccharide resulted in disappearance of DCs from
      the renal interstitium within 48 hours. This was accompanied by increased renal
      lymph node DCs, some of which contained intracellular Tamm-Horsfall Protein,
      indicating abnormal trafficking of kidney-specific antigens following renal
      injury. Lipopolysaccharide enhanced DC-mediated proliferation of ovalbumin
      specific CD4(+ve) T-cells within the draining RLN. Unilateral renal ischemia
      augmented the capacity for DC-mediated T-cell activation in the lymph nodes
      draining both the ischemic and nonischemic kidney. CONCLUSION: Renal DCs respond
      to systemic or localized acute renal injury by increasing the traffic of protein
      antigens from kidney to RLN, resulting in a concomitant increased potential for
      localized activation of antigen-specific CD4(+ve) T-cells.

PMID- 16105041
TI  - Podocyte involvement in human immune crescentic glomerulonephritis.
AB  - BACKGROUND: The role of podocytes in human crescentic glomerulonephritis (GN) has
      been underestimated. This may be due to the confounding fact that "dysregulated"
      podocytes are able to proliferate, lose their markers, and acquire new epitopes.
      Moreover, in experimental anti-glomerular basement membrane (GBM) crescentic GN,
      podocytes participate in the crescent formation. The aim of this study was to
      investigate the involvement of podocytes in human immune crescentic GN. METHODS:
      Renal biopsies from 12 patients with anti-GBM disease and 14 with class IV lupus
      GN were studied by immunohistochemistry for the following markers: (1)
      synaptopodin, GLEPP1, podocalyxin, podocin, alpha-actinin-4, and vimentin for
      podocyte identification; (2) PCNA, Ki-67, and p57 for cell cycle assessment; (3)
      cytokeratins for identifying epithelial cells but not normal podocytes; (4) CD68
      for tagging a macrophagic epitope; (5) alpha-smooth-muscle actin (alpha-SMA), a
      phenotypic marker of myofibroblasts. RESULTS: "True" (capsular) crescents lining
      Bowman's capsule and (tuft) "pseudocrescents" covering the glomerular tuft with a
      persistent patent urinary space were present in the 2 types of crescentic GN in
      similar percentages. Several features indicated that podocytes were involved in
      the formation of the both crescent types. Identifiable podocytes expressed
      proliferation markers. Podocyte cytoplasmic expansions and racket-like podocytes
      bridged between the tuft and Bowman's capsule. True and pseudocrescents contained
      labeled podocytes. In addition, podocytes located outside of the crescents had
      often lost their markers (dedifferentiation) and acquired new epitopes
      (cytokeratins and CD68). CONCLUSION: In human immune crescentic GN, podocytes
      undergo proliferation and dysregulation that are indicative of a podocytopathy.
      Podocytes contribute to crescent formation.

PMID- 16105042
TI  - Is the nephritogenic antigen in post-streptococcal glomerulonephritis pyrogenic
      exotoxin B (SPE B) or GAPDH?
AB  - BACKGROUND: Acute glomerulonephritis can follow infection by group A
      streptococci. An immune-complex pathogenesis is accepted, but the causative
      antigen(s) is still controversial. In recent years, 2 streptococcal antigens, the
      cationic cysteine proteinase exotoxin B (SPE B) and the plasmin receptor, a
      glyceraldehyde phosphate dehydrogenase (Plr, GAPDH) have attracted attention
      because: (1) they were localized in glomeruli in patients with acute post
      streptococcal glomerulonephritis (APSGN); and (2) serum antibody to these
      antigens was associated with nephritogenic streptococcal infections. To date,
      putative nephritogens were always tested independently. Here, the relevance of
      SPE B and GAPDH was evaluated in the same renal biopsies and serum samples of
      well-defined APSGN patients. METHODS: Renal biopsies (17 patients) and serum
      samples (53 patients) with APSGN and appropriate controls were examined.
      Immunofluorescent staining of frozen sections was performed using specific
      antibodies to SPE B and GAPDH. Serum antibodies were investigated by both enzyme
      linked immunosorbent assay (ELISA) and Western blot methodology. RESULTS:
      Glomerular deposits of SPE B were demonstrated in 12/17 APSGN biopsies, and 2
      cases were borderline; circulating antibodies were found in all instances (53/53
      patients). Glomerular deposition of GAPDH was detected in 1/17 biopsies, and 2
      cases were borderline; circulating antibodies were found in 5/47 patients. In 31
      control biopsies, only weak staining for each antigen was found in 2 cases.
      CONCLUSION: In this study, glomerular deposits of and antibody response to
      zymogen/SPE B are more consistently present in APSGN than deposits and antibody
      response to GAPDH. Zymogen/SPE B is likely to be the major antigen involved in
      the pathogenesis of most cases of APSGN.

PMID- 16105043
TI  - Immunohistochemical localization of apolipoprotein A-IV in human kidney tissue.
AB  - BACKGROUND: Apolipoprotein A-IV (ApoA-IV) is a 46 kD glycoprotein thought to
      protect against atherosclerosis. It is synthesized primarily in epithelial cells
      of the small intestine. Elevated plasma concentrations of ApoA-IV in patients
      with chronic kidney disease suggest that the human kidney is involved in ApoA-IV
      metabolism. METHODS: To investigate whether the human kidney directly metabolizes
      ApoA-IV and which kidney tissue compartment is involved therein, ApoA-IV was
      localized by immunohistochemistry in 28 healthy kidney tissue samples obtained
      from patients undergoing nephrectomy. ApoA-IV mRNA expression was analyzed by
      real-time polymerase chain reaction (PCR) to exclude de novo synthesis in the
      kidney. RESULTS: ApoA-IV immunostaining was detected in proximal and distal
      tubular cells, capillaries and blood vessels but not inside glomeruli. ApoA-IV
      was predominantly found in the brush border of proximal tubules and in
      intracellular granules and various plasma membrane domains of both proximal and
      distal tubules. mRNA expression analysis revealed that no ApoA-IV was produced in
      the kidney. CONCLUSION: The immunoreactivity of ApoA-IV observed in kidney
      tubular cells suggests a direct role of the human kidney in ApoA-IV metabolism.
      The granular staining pattern probably represents lysosomes degrading ApoA-IV.
      The additional ApoA-IV localization in distal tubules suggests a rescue function
      to reabsorb otherwise escaping ApoA-IV in case proximal tubules cannot reabsorb
      all ApoA-IV. Since no mRNA expression could be detected in any kidney cells, the
      observed ApoA-IV immunoreactivity represents uptake and not de novo synthesis of
      ApoA-IV.

PMID- 16105044
TI  - Role of membrane microdomains in PTH-mediated down-regulation of NaPi-IIa in
      opossum kidney cells.
AB  - BACKGROUND: Parathyroid hormone (PTH) rapidly down-regulates type IIa sodium
      dependent phosphate transporter (NaPi-IIa) via an endocytic pathway. Since the
      relationship between PTH signaling and NaPi-IIa endocytosis has not been
      explored, we investigated the role of membrane microdomains in this process.
      METHODS: We examined the submembrane localization of NaPi-IIa in opossum kidney
      (OK-N2) cells that stably expressed human NaPi-IIa, and searched for a PTH
      induced specific phosphorylating substrate on their membrane microdomains by
      immunoblotting with specific antibody against phospho substrates of protein
      kinases. RESULTS: We found that NaPi-IIa was primarily localized in low-density
      membrane (LDM) domains of the plasma membrane; PTH reduced the levels of
      immunoreactive NaPi-IIa in these domains. Furthermore, PTH activated both protein
      kinase A (PKA) and protein kinase Calpha (PKCa) and increased the phosphorylation
      of 250 kD and 80 kD substrates; this latter substrate was identified as ezrin,
      which a member of the ezrin-radixin-moesin (ERM) protein family. In response to
      PTH, ezrin was phosphorylated by both PKA and PKC. Dominant negative ezrin
      blocked the reduction in NaPi-IIa expression in the LDM domains that was induced
      by PTH. CONCLUSION: These data suggest that NaPi-IIa and PTH-induced
      phosphorylated proteins that include ezrin are compartmentalized in LDM
      microdomains. This compartmentalization may play an important role in the down
      regulation of NaPi-IIa via endocytosis.

PMID- 16105045
TI  - Effect of fibroblast growth factor-23 on phosphate transport in proximal tubules.
AB  - BACKGROUND: Fibroblast growth factor-23 (FGF-23) has been implicated in the renal
      phosphate wasting in tumor-induced osteomalacia, X-linked hypophosphatemia, and
      autosomal-dominant hypophosphatemic rickets. METHODS: In this in vitro
      microperfusion study we examined if FGF23R176Q, a stable mutant of FGF-23,
      impairs phosphate transport in rabbit proximal convoluted and proximal straight
      tubules perfused in vitro. We also examined if heparin, a molecule that is known
      to facilitate binding of FGFs to their receptor was necessary for the action of
      FGF23R176Q on transport. RESULTS: In the presence of heparin, FGF23R176Q reduced
      phosphate transport from 10.8 +/- 2.0 to 9.9 +/- 1.9 pmol/mm/min in proximal
      convoluted tubules and 1.0 +/- 0.2 to 0.8 +/- 0.2 pmol/mm/min in proximal
      straight tubules (both P < 0.05). There was no effect of FGF23R176Q in the
      absence of heparin. Incubation of finely minced mouse renal cortical tissue in
      tissue culture media for 3 hours resulted in a reduction in brush border membrane
      vesicles (BBMV) sodium-dependent phosphate transport (NaPi-2A) protein abundance
      in the presence but not in the absence of heparin. CONCLUSION: These data
      demonstrate that the inhibition of phosphate transport by FGF23R176Q in vitro
      requires heparin. The action of FGF23R176Q is associated with a reduction in BBMV
      NaPi-2A protein abundance.

PMID- 16105046
TI  - Racial differences in renal arteriolar structure in children with minimal change
      nephropathy.
AB  - BACKGROUND: African Americans are at increased risk for hypertension and chronic
      renal disease. Some data suggest this results from renal microvascular disease.
      The aim of this study was to determine if renal vascular changes were more
      pronounced in African Americans, were independent of blood pressure, and occurred
      in early childhood. METHODS: We performed morphometric analysis on small cortical
      arteries and arterioles from 44 renal biopsies done in African American and white
      children (mean age 8.4 +/- SD 5.0 years) with minimal change nephropathy. Outer
      and inner vessel diameters were measured and wall:lumen and wall:outer diameter
      ratios (WT/OD) calculated. Clinical data on blood pressure, steroid use, serum
      creatinine, gender, age, and proteinuria were abstracted by chart review. A z
      score for systolic and diastolic blood pressure was calculated. Follow-up
      clinical data were available for 11 children. Data were compared using analysis
      of covariance (ANCOVA) and t test for paired data. RESULTS: Lumen diameters of
      African Americans were 3.1 microm (23%) smaller that those of white children (P =
      0.024). Similarly, their WT/OD was greater than in the whites, 0.31+/-0.03 vs.
      0.28 +/- 0.02 (P= 0.048). These changes were independent of age, steroid use,
      systolic blood pressure and diastolic blood pressure z scores. Follow-up data
      showed a rise in serum creatinine (>50%) in five patients, +1.42 +/- 0.79 mg/dL
      (P = 0.016), of whom four were African American. There was no change in blood
      pressure. CONCLUSION: The renal arterioles of African American children with
      minimal change nephropathy exhibit significantly smaller lumens and thicker walls
      than white children. The changes occur very early in life and are independent of
      age, blood pressure, and steroid use. Such changes may contribute to the African
      American predisposition to chronic renal disease and hypertension.

PMID- 16105047
TI  - Hypertension in Page (cellophane-wrapped) kidney is due to interstitial
      nephritis.
AB  - BACKGROUND: Cellophane wrapping of the kidneys (Page kidney) induces perinephrits
      and hypertension, assumed to be due to renal ischemia resulting from parenchymal
      compression by the fibrous hull surrounding the kidneys. We investigated if
      interstitial nephritis, rather than plasma angiotensin activity, played a role in
      the development of hypertension in the Page kidney model. METHODS: We followed
      for 7 weeks rats with bilateral cellophane wrapping of the kidneys that received
      20 mg/kg/day of the immunosuppressive antiproliferative drug mycophenolate
      mofetil (MMF) (two-kidney wrap/MMF) (N = 10) or vehicle (two-kidney wrap) (N =
      10), and sham-operated rats (N = 10). RESULTS: The two-kidney wrap group had
      progressive increment in blood pressure, inflammatory damage occupying 25% to 50%
      of the renal tubulointerstitial region and increased number of angiotensin II
      positive cells, angiotensin II content, and oxidative stress in the kidney. MMF
      treatment prevented the development of hypertension and renal inflammation
      without modifying the perinephritic hull or the increment it induced in the
      intrarenal pressure. The plasma levels of angiotensin II were similar in the two
      kidney wrap group, the two-kidney wrap/MMF group and the sham-operated animals
      and unchanged from baseline, despite the blood pressure increase in the two
      kidney wrap group. CONCLUSION: Our results indicate that renal wrap hypertension
      is unrelated to plasma angiotensin II levels and related to the inflammatory
      damage caused by the external compression of the kidney.

PMID- 16105048
TI  - Differential connexin expression in preglomerular and postglomerular vasculature:
      accentuation during diabetes.
AB  - BACKGROUND: Gap junctions may play an important role in regulating renal blood
      flow and glomerular responses. We have therefore made a comprehensive analysis of
      connexin expression in the renal vasculature of control and diabetic mice since
      elevated glucose has been reported to down-regulate connexin 43 in vascular cells
      in vitro. METHODS: Connexin distribution was determined with immunohistochemistry
      using subtype-specific and cell type-specific antibodies. Diabetes was induced
      with streptozotocin (120/80 mg/kg, intraperitoneally) in C57BL/6 mice. RESULTS:
      Connexins 37, 40, and 43 were expressed in endothelial cells of the renal, lobar,
      arcuate, and interlobular arteries and afferent arterioles, although connexin 43
      was weak in the renal and arcuate arteries. Connexin 37 was detected in the media
      of arcuate, interlobular arteries and afferent arterioles and connexins 37 and 40
      were found in renin-secreting cells. Both connexins 37 and 40 were expressed in
      extraglomerular mesangial cells, connexin 40 was abundantly expressed in
      intraglomerular mesangial cells, but connexin 37 was limited to mesangial cells
      at the vascular pole. In contrast, only connexin 43 was detected in endothelial
      cells of efferent arterioles and there was no connexin staining in the media. In
      diabetes, connexin 40 was expressed in smooth muscle cells along afferent
      arterioles, glomerular connexin staining was more extensive and connexin 43 was
      detected in renin-secreting cells. In contrast connexin 43 expression in
      endothelial cells of efferent arterioles was markedly reduced. CONCLUSION: The
      renal vasculature and mesangial cells are well coupled on the preglomerular side
      but there is little evidence that the coupling extends into the efferent
      arteriole. This pattern of cell coupling is accentuated during diabetes.

PMID- 16105049
TI  - Renin-angiotensin polymorphisms and QTc interval prolongation in end-stage renal
      disease.
AB  - BACKGROUND: Polymorphisms of renin-angiotensin system (RAS) genes in patients
      with end-stage renal disease (ESRD) on chronic hemodialysis may be associated
      with QTc interval prolongation, leading to fatal arrhythmias. The objective of
      this study was to determine (1) the prevalence of QTc prolongation in
      hemodialysis patients, and (2) the association of a prolonged QTc in these
      patients with RAS polymorphisms [angiotensin-converting enzyme-insertion/deletion
      (ACE-I/D), angiotensin type 1 receptor-A1166C (AT1R-A1166C), and angiotensinogen
      M235T (AGT-M235T)]. METHODS: Twelve-lead electrocardiograms (ECGs), serum
      electrolytes (sodium, potassium, and calcium), and ACE and angiotensin II levels
      were obtained 10 to 12 hours after a hemodialysis session in 43 patients with
      ESRD on chronic hemodialysis [mean age (+/-SD), 55 +/- 14 years]. Using
      polymerase chain reaction (PCR), the presence of polymorphisms of the ACE-I/D,
      AT1R-A1166C, and AGT-M235T genes was determined from the buccal cells. A maximum
      QT interval in patients with sinus rhythm and normal QRS duration was corrected
      for heart rate using Hodges' formula. RESULTS: Fifty-eight percent of the
      patients had QTc interval prolongation (>440 msec). The ACE-DD genotype (P =
      0.002) and the C allele of the AT1R-A1166C gene (P = 0.004), but not the AGT
      M235T gene, contributed to QTc prolongation. CONCLUSION: Polymorphisms of ACE and
      AT1R genes additively contribute to QTc prolongation found in a great majority of
      ESRD patients. Therefore, ESRD patients with both or one of these polymorphisms
      may be at a higher risk for sudden cardiac death.

PMID- 16105050
TI  - Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with
      type 2 diabetes and microalbuminuria.
AB  - BACKGROUND: The purpose of this study was to evaluate the renoprotective effect
      as reflected by short-term changes in albuminuria of ultrahigh doses of
      irbesartan in type 2 diabetic patients with microalbuminuria. METHODS: This
      double-masked randomized crossover trial included 52 (41 males) hypertensive type
      2 diabetic patients with microalbuminuria on ongoing antihypertensive medication.
      At inclusion, previous antihypertensive treatment was discontinued and replaced
      with bendroflumethiazide, 5 mg once daily, for the entire study. Following 2
      months wash-out (baseline), patients were treated randomly with irbesartan 300,
      600, and 900 mg once daily, each dose for 2 months. End points evaluated at the
      end of each study period included urinary albumin excretion rate (UAE) (mean of
      three 24-hour collections), 24-hour ambulatory blood pressure, and glomerular
      filtration rate (GFR) [chromium 51 ethylenediaminetetraacetic acid (51Cr-EDTA)].
      RESULTS: Baseline values were: 24-hour UAE [geometric mean (95% CI)] 134 (103 to
      170) mg/24 hours, ambulatory blood pressure [mean (SD)] 140 (10)/77 (7) mm Hg,
      and GFR 103 (19) mL/min/1.73 m2. All doses of irbesartan significantly reduced
      UAE, ambulatory blood pressure, and GFR from baseline. Reductions in UAE from
      baseline were 52% (46% to 57%), 49% (43% to 54%), and 59% (54% to 63%) with
      increasing doses of irbesartan (P < 0.01). UAE was reduced significantly more by
      irbesartan 900 mg compared with lower doses with an additional reduction in UAE
      of 15% (2% to 26%) by irbesartan 900 mg compared with 300 mg (P = 0.02). The
      greater reduction in albuminuria by irbesartan 900 vs. 300 mg was more pronounced
      in patients with UAE during irbesartan 300 mg above vs. below the median [31%
      (18% to 42%) vs. -9% (-25% to 6%), respectively (P < 0.05)]. With increasing
      doses systolic ambulatory blood pressure was reduced from baseline by 8 (4 to
      12), 9 (5 to 13), and 9 (5 to13) mm Hg, and diastolic ambulatory blood pressure
      by 6 (4 to 7), 7 (6 to 9), and 7 (6 to 9) mm Hg (NS between doses). CONCLUSION:
      Ultrahigh dosing of irbesartan (900 mg once daily) is generally safe and offers
      additional renoprotection independent of changes in systemic blood pressure and
      GFR in comparison to the currently recommended dose of 300 mg.

PMID- 16105051
TI  - Predictors of survival in anuric peritoneal dialysis patients.
AB  - BACKGROUND: Residual glomerular filtration rate (GFR) is a much more important
      determinant of survival in peritoneal dialysis patients, than peritoneal solute
      clearances. However, anuric peritoneal dialysis patients are solely dependent on
      peritoneal solute clearances. The aim of the study was to analyze the effects of
      peritoneal small solute clearances and ultrafiltration on survival in anuric
      patients, and to establish the minimum levels of small solute clearances and net
      ultrafiltration. These objectives were investigated in a prospective cohort study
      in incident peritoneal dialysis patients who had become anuric during follow-up.
      METHODS: The Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)
      is a prospective multicenter cohort study in which new adult dialysis patients
      are included and followed during 6 months intervals. Included were 542 peritoneal
      dialysis patients. Of these, 166 developed anuria, 130 of which could be included
      in the study. RESULTS: Two-year patient survival after the outset of anuria was
      67%, technique survival 73%, and the combined 2-year patient and technique
      survival was 50%. Risk factors associated with mortality were age, comorbidity,
      the duration of peritoneal dialysis before anuria, and a low serum albumin.
      Peritoneal solute clearances were analyzed time-dependently. These parameters
      were not associated with survival when analyzed as continuous variables and also
      not when the analyses were done in quintiles, although the time-dependent
      approach was almost significant for Kt/V(urea). On the other hand, when the
      results were analyzed dichotomously using predefined cutoff points, Kt/V(urea)
      <1.5 per week and creatinine clearance <40 L/week/1.73 m2 were associated with an
      increase in the relative risk of death. Also peritoneal ultrafiltration was
      significantly associated with survival. CONCLUSION: The survival of anuric
      peritoneal dialysis patients is in line with expectations based on the duration
      of dialysis. The risk factors for death are the same as in the dialysis
      population as a whole. Besides an association with ultrafiltration, our study
      enabled us to define the lower limits of adequate peritoneal dialysis, that is
      Kt/V(urea) <1.5 per week and creatinine clearance <40 L/week/1.73 m2.

PMID- 16105052
TI  - Specific measurement of PTH (1-84) in various forms of renal osteodystrophy (ROD)
      as assessed by bone histomorphometry.
AB  - BACKGROUND: Parathyroid hormone (PTH) measurements serve as a noninvasive,
      diagnostic tool for the assessment of renal osteodystrophy (ROD). Their value has
      been questioned following reports indicating that all commercially available
      intact PTH (I-PTH) assays cross-react with amino terminally truncated PTH
      fragments. Because these fragments can account for 50% of total PTH, their
      detection will overestimate the true PTH concentration and may lead to diagnostic
      inaccuracies. The aim of this study was to evaluate the specific Bio-Intact PTH
      (1-84) Assay (BI-PTH) in patients with various types of ROD confirmed by bone
      biopsy. METHODS: Bone biopsies were taken from 132 patients with chronic kidney
      disease (CKD) stages 3 to 5, and quantitative bone histomorphometry was done.
      Plasma PTH levels were measured using both the BI-PTH and I-PTH assays on an
      automated analyzer. RESULTS: Patients with CKD stages 3/4 and low turnover
      skeletal lesions had BI-PTH values (pg/mL, mean +/- SD) of 35 (+/-34) and I-PTH
      values of 59 (+/- 63). Corresponding values for BI-PTH and I-PTH in those with
      high turnover lesions were 141 (+/-60) and 221 (+/-106). Patients with CKD stage
      5 and low turnover skeletal lesions had BI-PTH and I-PTH levels of 51 (+/-38) and
      90 (+/-60), respectively, whereas the corresponding results for BI-PTH and I-PTH
      in those with high turnover lesions were 237 (+/-214) and 461 (+/-437). The areas
      under the receiver operating characteristic (ROC) curves for distinguishing low
      turnover from high turnover lesions were 0.94 for BI-PTH and 0.91 for I-PTH in
      CKD stages 3/4 and 0.86 for BI-PTH and 0.85 for I-PTH in CKD stage 5. Among all
      patients, BI-PTH levels are approximately 50% lower than I-PTH levels, but the
      results of the two assays are correlated highly (R2 = 0.92). CONCLUSION: Plasma
      PTH measurements using either the BI-PTH or I-PTH assay effectively identify
      patients with reduced bone turnover and serve to distinguish this subgroup from
      those with high turnover lesions of renal bone disease. Both assays provide
      better diagnostic discrimination for this purpose than calculated values for the
      ratio of PTH (1-84)/amino terminally truncated PTH fragments.

PMID- 16105053
TI  - Incidence of recombinant erythropoietin (EPO) hyporesponse, EPO-associated
      antibodies, and pure red cell aplasia in dialysis patients.
AB  - BACKGROUND: Since 1998, an increase of anti-erythropoietin (anti-EPO) antibody
      induced pure red cell aplasia (PRCA) has been reported. As data up to now
      consisted mostly of spontaneously reported cases the question arose about the
      frequency of this increase in EPO-induced PRCA. The objectives of this study were
      to determine the incidence and causes of recombinant EPO hyporesponse, of
      antibodies to EPO in patients on dialysis, and to relate the detection of anti
      EPO antibodies to the presence of PRCA. METHOD: This multicenter cohort study
      used existing patient data and serum samples collected at 6-month intervals from
      1677 patients with incident end-stage renal disease (ESRD) participating in The
      Netherlands Cooperative Study on the Adequacy of Dialysis-2 (NECOSAD-2). RESULTS:
      Fifty-seven patients had an inadequate EPO response, which resulted in an
      incidence of 16.7 per 1000 patient-years on EPO while on dialysis. All available
      sera specimens (N = 232) of these patients were screened for anti-EPO antibodies.
      The sera specimens of two of these 57 patients tested positive. Of the 57
      patients with inadequate EPO response, one had clinical PRCA (incidence 0.29 per
      1000 patient-years on EPO and on dialysis). Of the 1346 patients without symptoms
      of inadequate EPO response, one patient tested borderline positive for anti-EPO
      antibodies. In total, three patients developed EPO antibodies during follow-up,
      leading to an estimated incidence of 1.27/1000 (95% CI 0.3 to 3.7/1000) patient
      years since the start of dialysis. CONCLUSION: The incidence of inadequate EPO
      response in our population of dialysis patients is in concordance with tentative
      calculations found in the literature. Furthermore, we found the incidence of EPO
      induced PRCA and EPO antibodies to be low.

PMID- 16105054
TI  - In uremia, plasma levels of anti-protein C and anti-protein S antibodies are
      associated with thrombosis.
AB  - BACKGROUND: Vascular access thrombosis is an important cause of morbidity in
      patients with end-stage renal failure on maintenance hemodialysis (MHD). However,
      little is known about its risk factors. The present study was undertaken to
      evaluate the role of coagulation factors, fibrinolytic factors, and anti
      phospholipid antibodies (aPL). In particular, we have evaluated the role of anti
      protein C and anti-protein S antibodies in patients on MHD with and without
      thrombosis because no data are available in the literature. METHODS: The study
      group comprised 30 patients with thrombotic complications (TC), 40 patients
      matched for age, sex, and dialytic age with no thrombotic complications (NTC) and
      400 controls. We have measured: anti-protein C antibodies, anti-protein S
      antibodies, anticardiolipin antibodies (ACA), anti-beta2-glycoprotein antibodies
      (beta2-GPI), and anti-prothrombin antibodies (aPT), along with prothrombin time,
      fibrinogen, plasminogen, protein C, protein S, anti-thrombin III, APC-resistance
      test, D-dimer, tissue-type plasminogen's activator, plasminogen activator
      inhibitor-1 (PAI-1), prothrombin fragment 1+2, factors of the intrinsic and
      extrinsic pathway, C-reactive protein, and homocysteine. RESULTS: There were no
      significant differences between groups for prothrombin time, fibrinogen,
      plasminogen, protein C, protein S, anti-thrombin III, activated protein C (APC)
      resistance, D-dimer, tPA, C-reactive protein, Factors II, X, and VII. The anti
      beta2-GP1 and aPT were elevated in both TC and NTC patients, compared to the
      control group. Significant differences between TC and NTC groups were found for
      anti-protein C and anti-protein S antibodies, ACA-IgM, PAI-1, Factor VIII,
      prothrombin fragments 1+2, and homocysteine. CONCLUSION: The most novel finding
      was a significant elevation of anti-protein C antibodies and anti-protein S
      antibodies in the TC group (i.e., in patients on MHD with thrombosis of vascular
      access). It indicates that other pathogenetic mechanisms in addition to
      endothelial damage may cause hypercoagulability in uremia.

PMID- 16105055
TI  - Diabetes mellitus and the risk of nephrolithiasis.
AB  - BACKGROUND: Insulin resistance is a central feature of type 2 diabetes mellitus
      (DM) and may increase the risk of kidney stone formation. Existing cross
      sectional data on the association between DM and nephrolithiasis are limited, and
      no prospective study to date has evaluated the relation between DM and the risk
      of kidney stones. METHODS: To evaluate the relation between DM and prevalent
      kidney stones, we conducted a cross-sectional study of 3 large cohorts including
      over 200,000 participants: the Nurses' Health Study I (older women), the Nurses'
      Health Study II (younger women), and the Health Professionals Follow-up Study
      (men). We then prospectively studied the association between DM and incident
      nephrolithiasis over a combined 44 years of follow-up. Because insulin resistance
      can precede the diagnosis of DM by decades, we also prospectively examined the
      relation between kidney stones and the diagnosis of incident DM. Multivariate
      regression models adjusted for age, body mass index, thiazide diuretic use, fluid
      intake, and dietary factors. RESULTS: At baseline, the multivariate relative risk
      of prevalent stone disease in individuals with DM compared to individuals without
      was 1.38 (95% CI 1.06-1.79) in older women, 1.67 (95% CI 1.28-2.20) in younger
      women, and 1.31 (95% CI 1.11-1.54) in men. Prospectively, the multivariate
      relative risk of incident kidney stone formation in participants with DM compared
      to participants without was 1.29 (95% CI 1.05-1.58) in older women, 1.60 (95% CI
      1.16-2.21) in younger women, and 0.81 (95% CI 0.59-1.09) in men. The multivariate
      relative risk of incident DM in participants with a history of kidney stones
      compared to participants without was 1.33 (95% CI 1.18-1.50) in older women, 1.48
      (95% CI 1.14-1.91) in younger women, and 1.49 (95% CI 1.29-1.72) in men.
      CONCLUSION: DM is a risk factor for the development of kidney stones. Additional
      studies are needed to determine if the increased risk of DM in stone formers is
      due to subclinical insulin resistance.

PMID- 16105056
TI  - First- and second-generation immunometric PTH assays during treatment of
      hyperparathyroidism with cinacalcet HCl.
AB  - BACKGROUND: First-generation immunometric assays for "intact" parathyroid hormone
      (iPTH) also measure large N-terminally truncated PTH fragments, whereas second
      generation assays, such as the "bio-intact" PTH (biPTH) assay, measure only full
      length biologically active PTH(1-84). This study compared iPTH and biPTH assays
      during cinacalcet treatment in subjects with secondary HPT receiving dialysis.
      METHODS: Four hundred and ten subjects were enrolled in a 26-week randomized,
      double-blind, placebo-controlled trial of oral cinacalcet (or placebo), 30 to 180
      mg once daily, and efficacy was assessed using biPTH and iPTH assays. RESULTS:
      Compared with control treatment, cinacalcet improved the management of secondary
      HPT. Both biPTH and iPTH decreased by 38%+/- 3% during weeks 13 to 26 in the
      cinacalcet group; biPTH increased by 23%+/- 4% and iPTH increased by 9.5%+/- 3%
      in the control group (P < 0.001). Fifty-six percent of cinacalcet subjects and
      10% of control subjects had a > or = 30% reduction in biPTH, and 61% and 11%,
      respectively, had a > or = 30% reduction in iPTH. Significant correlations
      between biPTH and iPTH levels were observed throughout the study. Both assays
      correlated similarly with bone-specific alkaline phosphatase levels. The ratio of
      biPTH to iPTH was maintained at 56% +/- 1% after treatment in both treatment
      groups. Increasing serum calcium levels were associated with a decreasing ratio
      of biPTH to (iPTH-biPTH). CONCLUSION: These data show that PTH can be monitored
      with either iPTH or biPTH assays during therapy with cinacalcet, and that
      cinacalcet therapy does not exert a major influence on the ratio between PTH(1
      84) and large, N-terminally truncated PTH fragments.

PMID- 16105057
TI  - Use of a probiotic to decrease enteric hyperoxaluria.
AB  - BACKGROUND: Patients with inflammatory bowel disease have a 10- to 100-fold
      increased risk of nephrolithiasis, with enteric hyperoxaluria being the major
      risk factor for these and other patients with fat malabsorptive states.
      Endogenous components of the intestinal microflora can potentially limit dietary
      oxalate absorption. METHODS: Ten patients were studied with chronic fat
      malabsorption, calcium oxalate stones, and hyperoxaluria thought to be caused by
      jejunoileal bypass (1) and Roux-en-Y gastric bypass surgery for obesity (4),
      dumping syndrome secondary to gastrectomy (2), celiac sprue (1), chronic
      pancreatitis (1), and ulcerative colitis in remission (1). For 3 months, patients
      received increasing doses of a lactic acid bacteria mixture (Oxadrop), VSL
      Pharmaceuticals), followed by a washout month. Twenty-four-hour urine collections
      were performed at baseline and after each month. RESULTS: Mean urinary oxalate
      excretion fell by 19% after 1 month (1 dose per day, P < 0.05), and oxalate
      excretion remained reduced by 24% during the second month (2 doses per day, P <
      0.05). During the third month on 3 doses per day oxalate excretion increased
      slightly, so that the mean was close to the baseline established off treatment.
      Urinary oxalate again fell 20% from baseline during the washout period. Calcium
      oxalate supersaturation was reduced while on Oxadrop, largely due to the decrease
      in oxalate excretion, although mean changes did not reach statistical
      significance. CONCLUSION: Manipulation of gastrointestinal (GI) flora can
      influence urinary oxalate excretion to reduce urinary supersaturation levels.
      These changes could have a salutary effect on stone formation rates. Further
      studies will be needed to establish the optimal dosing regimen.

PMID- 16105058
TI  - Improved prognosis in type 1 diabetic patients with nephropathy: a prospective
      follow-up study.
AB  - BACKGROUND: In early studies, a median survival time of 5 to 7 years from onset
      of diabetic nephropathy was observed. Furthermore, end-stage renal disease (ESRD)
      was the main cause of death. We prospectively assessed the impact of reno- and
      cardiovascular protective treatment on prognosis in type 1 diabetic patients with
      diabetic nephropathy. METHODS: We prospectively followed 199 type 1 diabetic
      patients with diabetic nephropathy and 192 patients with normoalbuminuria for 10
      years. Aggressive antihypertensive treatment was initiated in patients with
      diabetic nephropathy in mid 1980s, whereas statins and aspirin were not
      prescribed routinely until April 2002. The primary end point was cardiovascular
      mortality and morbidity. Secondary end points were all-cause mortality and ESRD.
      RESULTS: During follow-up, 79 patients (40%) with nephropathy reached the primary
      end point versus 19 (10%) of normoalbuminuric patients, log rank test P < 0.0001.
      Predictors of the primary end point were: nephropathy (hazard ratio 3.26; 95%
      confidence interval 1.89 to 5.62), previous event (3.19; 2.04 to 4.97), age
      (1.27; 1.04 to 1.55), and systolic blood pressure (1.13; 1.03 to 1.24). In the
      nephropathy group, 60 patients (30%) died; hereof, 25 deaths (42%) were ascribed
      to cardiovascular causes while 30 patients (50%) with nephropathy died with ESRD.
      The estimate of median survival time from onset of diabetic nephropathy was 21.7
      years, SE 3.3 years. CONCLUSION: The survival of patients with diabetic
      nephropathy has improved most likely due to aggressive antihypertensive treatment
      and improved glycaemic control.

PMID- 16105059
TI  - Progression of coronary artery calcification in diabetics with and without
      chronic kidney disease.
AB  - BACKGROUND: Rapid progression of coronary artery calcification (CAC) has been
      reported among individuals with end-stage renal disease (ESRD). There is limited
      information on the progression of CAC during earlier stages of diabetic chronic
      kidney disease (CKD). METHODS: In a prospective, cohort study of type 2 diabetic
      individuals (N = 90; normoalbuminuric diabetic controls, 30; diabetic
      nephropathy, DN, 60), electron-beam computed tomography (EBCT) was repeated at an
      average interval of 19 months. All scan images were acquired at end-systole to
      minimize interscan variability. In order to eliminate the dependence of the
      residual error from interscan variability on baseline CAC scores, square root
      transformed CAC scores were used for analyses of progression of coronary
      calcification. RESULTS: Repeat EBCT scans were completed in 68 subjects (diabetic
      controls: 23; DN: 45). There was a highly significant relationship between the
      proportion of subjects with progressive CAC and renal disease-DN who progressed
      to ESRD, 80%; DN who did not progress to ESRD, 30%; and diabetic controls, 13% (P
      < 0.001). Similarly, the magnitude of change was significantly related to renal
      disease (DN who progressed to ESRD > DN who did not progress to ESRD > diabetic
      controls, P < 0.001). Using logistic regression and controlling for non-dialyzed
      DN, ESRD and inter-scan interval, advanced age was the only significant variable
      associated with progression of CAC. Finally, serum creatinine and baseline CAC
      score emerged as independent predictors for the magnitude of increase in CAC.
      CONCLUSION: Progression of CAC is apparent among individuals with DN both before
      and after ESRD. However, the risk factors associated with progression of CAC may
      differ at different stages of CKD.

PMID- 16105060
TI  - Predominant effect of kidney disease on mortality in Pima Indians with or without
      type 2 diabetes.
AB  - BACKGROUND: We examined the effect of kidney disease (KD) on mortality in
      nondiabetic and diabetic Pima Indians aged > or = 45 years old. METHODS: Deaths
      and person-years of follow-up were stratified in a time-dependent fashion into
      categories of (1) no proteinuria and normal serum creatinine (SCr); (2)
      proteinuria and normal SCr; (3) high SCr [SCr > or = 133 micromol/L (1.5 mg/dL)
      in men, > or = 124 micromol/L (1.4 mg/dL) in women] but not on renal replacement
      therapy (RRT); or (4) RRT. RESULTS: Among 1993 subjects, 55.8% had type 2
      diabetes at baseline. Overall death rates increased with declining kidney
      function in both the nondiabetic and diabetic subjects (P < 0.0001). Death rates
      were similar in nondiabetic and diabetic subjects with comparable levels of
      kidney function, although the number of deaths among nondiabetic subjects with
      advanced KD was small. Infections and malignancy were the leading causes of death
      in nondiabetic subjects with KD. Among diabetic subjects, overall mortality
      increased with diabetes duration (P = 0.0001) and was highest in those on RRT (P
      < 0.0001). High SCr was associated with higher death rates from cardiovascular
      disease (CVD), diabetic nephropathy (DN), infections, and malignancy. CONCLUSION:
      Death rates increased comparably with worsening kidney function in both
      nondiabetic and diabetic subjects and were similar in nondiabetic and diabetic
      subjects without KD. KD was associated with excess mortality from DN, CVD,
      infections, and malignancy in diabetic subjects, and from infections in those
      without diabetes.

PMID- 16105061
TI  - High incidence of initial and late steroid resistance in childhood nephrotic
      syndrome.
AB  - BACKGROUND: Conventional wisdom states that greater than 80% of children with
      nephrotic syndrome (NS) respond to steroid treatment, remain steroid-sensitive
      during subsequent relapses, and consequently have a favorable long-term
      prognosis. In contrast, steroid resistance is believed to be associated with a
      high risk of developing chronic renal failure. Recent reports suggest that the
      histologic pattern of NS in children may be changing, but whether the change is
      accompanied by a parallel change in steroid sensitivity is unknown. METHODS:
      Initial and subsequent steroid responsiveness was evaluated in all children aged
      1 to 18 years who presented with newly diagnosed NS to the 2 pediatric nephrology
      referral centers in southeastern Louisiana between 1994 and 2003. NS was defined
      as presence of edema, heavy proteinuria, and serum albumin concentration below
      2.5 g/dL. Steroid sensitivity (SS) was defined as total resolution of proteinuria
      and edema, and partial response to steroids (PR) was defined as loss of edema
      with continuing proteinuria. RESULTS: There were 210 new cases of NS. Forty-one
      patients (20%) had immune complex glomerulonephritis. Six patients were excluded
      because of incomplete data availability. Of the remaining 163 patients, 115 (71%)
      were SS and 23 (14%) achieved PR during the initial 4 weeks of treatment; 25
      (15%) were steroid-resistant (SR). Follow-up data were available for 91 of the
      115 initially SS patients; 19 subsequently became steroid-resistant. Thus, at
      least 45% of the patients with new-onset NS did not have typical childhood
      steroid-responsive NS. Initial steroid resistance was more likely in African
      American children and in children with older age at onset (11.5 vs. 4.6 years).
      Development of steroid resistance after initial SS was associated with shorter
      interval to the first relapse (2.2 vs. 5.4 months) and having the first relapse
      during the initial steroid treatment. CONCLUSION: Compared to previous reports,
      our results show a higher incidence of initial and subsequent steroid resistance,
      characteristics not consistent with typical minimal change NS with a benign
      prognosis. The results suggest that in the current era, NS in children may not be
      as benign as indicated by earlier studies.

PMID- 16105062
TI  - Factors associated with "do not resuscitate" orders and rates of withdrawal from
      hemodialysis in the international DOPPS.
AB  - BACKGROUND: Worldwide statistics on practice patterns regarding "do not
      resuscitate" (DNR) orders and patient withdrawal from hemodialysis have not been
      uniformly collected or analyzed. METHODS: Using data concerning adult
      hemodialysis patients randomly selected from 308 representative dialysis
      facilities in France, Germany, Italy, Japan, Spain, the United Kingdom, and the
      United States participating in the Dialysis Outcomes and Practice Patterns Study,
      DNR orders were tabulated at study entry from a prevalent cross-section of
      patients (N = 8615), using multivariate logistic regression to investigate
      characteristics associated with DNR status, Cox models to identify risk factors
      for withdrawal from hemodialysis, and scores from the mental component summary
      (MCS) and physical component summary (PCS) of the SF-36 to assess health-related
      quality of life. RESULTS: The United States had the highest prevalence of DNR
      orders (7.5%) and rate of withdrawal from hemodialysis (3.5 per 100 patient
      years). Significant and independent associations with higher odds ratio (OR) of
      DNR were observed for older age (OR 1.16 per 10 years higher, P = 0.03) and
      nursing home residence (OR 2.34, P = 0.003), and with higher relative risk (RR)
      of withdrawal from dialysis (RR 2.38, P < 0.001). Patients who withdrew from
      hemodialysis died within a mean of 7.8 days and a median of 6.0 days. CONCLUSION:
      The higher prevalence of DNR and rate of withdrawal from hemodialysis in the
      United States are consistent with its greater legal and cultural emphasis on
      patient autonomy. By showing characteristics associated with these outcomes, this
      study contributes to our understanding of why hemodialysis patients request DNR
      or withdraw from treatment.

PMID- 16105063
TI  - Albuminuria and incident coronary heart disease in Australian Aboriginal people.
AB  - BACKGROUND: It has been suggested that albuminuria is useful in identifying
      persons at increased risk of coronary heart disease (CHD). Australian Aborigines
      have exceedingly high rates of renal failure together with increased CHD
      mortality. We undertook this prospective cohort study to assess the independent
      effect of albuminuria on CHD risk in Aboriginal people in the Northern Territory
      of Australia. METHODS: We examined the relation between micro- and
      macroalbuminuria and incident CHD in a sample of 870 Aboriginal adults aged 20 to
      74 years old without prevalent baseline CHD. Cox proportional hazards models were
      used to assess the association between baseline albuminuria and CHD incidence.
      RESULTS: During a median of 9.2 years of follow-up, 89 CHD events occurred during
      the follow-up period (1992 to 2003). The incidence of CHD increased significantly
      across categories of albuminuria (4.4, 10.9, and 29.8 per 1000 person-years for
      normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively). The
      multiple Cox proportional hazards regression showed the hazard ratio was 3.4 (95%
      CI 1.6, 7.3), adjusting for age, gender, body mass index (BMI), blood pressure,
      total cholesterol, diabetes status, cigarette smoking, and alcohol consumption,
      for macroalbuminuria group. Hazard ratio for microalbuminuria group was not
      significantly different from unity during the first 6 years of follow-up but
      significantly higher during the follow-up period > or = 6 years with adjusted
      hazard ratio 9.0 (95% CI 2.0, 40.0). CONCLUSION: Independent of traditional
      cardiovascular risk factors, both microalbuminuria and macroalbuminuria may be
      useful in identifying persons at increased risk of CHD in Aboriginal people.

PMID- 16105064
TI  - Prognostic value of 24-hour ambulatory blood pressure monitoring and of night/day
      ratio in nondiabetic, cardiovascular events-free hemodialysis patients.
AB  - BACKGROUND: The use of 24-hour ambulatory blood pressure monitoring is increasing
      in end-stage renal disease (ESRD) patients but the prediction power for
      cardiovascular complications of time-averaged ambulatory blood pressure
      components has been little investigated in these patients. METHODS: We analyzed
      the prognostic power of 24-hour ambulatory blood pressure monitoring for all
      cause and cardiovascular mortality in 168 nondiabetic, events-free hemodialysis
      patients selected from a total dialysis population of about 450 patients.
      RESULTS: During the follow-up period (38 +/- 22 months), 48 patients died, 29 of
      them of cardiovascular causes. On univariate Cox regression analyses, the
      night/day systolic ratio resulted to be the sole blood pressure indicator to be
      associated with all-cause and cardiovascular mortality while left ventricular
      hypertrophy (LVH) was a strong predictor of these outcomes. In multivariable Cox
      models not including LVH, the night/day systolic ratio maintained an independent
      prognostic value for incident outcomes. However, when both risk factors, LVH and
      night/day systolic ratio, were introduced into Cox models, LVH was no longer a
      significant predictor while the night/day systolic ratio became a predictor of
      marginal statistical significance. CONCLUSION: The night/day ratio emerges as the
      sole ambulatory blood pressure monitoring-derived indicator providing significant
      prognostic information in patients with ESRD. However, this indicator as well as
      LVH loses substantial prediction power in statistical models including both risk
      factors. The results suggest that the night/day systolic ratio and LVH provide
      overlapping prognostic information, a phenomenon in keeping with the hypothesis
      that they represent a common pathway leading to adverse outcomes in ESRD.

PMID- 16105065
TI  - 3,4-di-deoxyglucosone-3-ene promotes leukocyte apoptosis.
AB  - BACKGROUND: Heat-sterilized, single-chambered, glucose-containing peritoneal
      dialysis solutions promote neutrophil apoptosis and impair the peritoneal
      antibacterial response. It has been proposed that glucose degradation products
      may be responsible for this effect. However, the precise contribution of
      individual glucose degradation products had not been addressed. METHODS: The
      effect of individual glucose degradation products on apoptosis in cultured human
      neutrophils and peripheral blood mononuclear cells was studied. RESULTS:
      Peritoneal dialysis solutions with a high content of both glucose and glucose
      degradation products accelerated neutrophil and mononuclear cell apoptosis. Among
      the different glucose degradation products, 3,4-di-deoxyglucosone-3-ene (3,4-DGE)
      accelerated apoptosis in neutrophils and peripheral blood mononuclear cells at
      concentrations (25 micromol/L) in the range found in heat-sterilized, single
      chambered, 4.25% glucose peritoneal dialysis fluids. Apoptosis induced by 3,4-DGE
      was caspase-dependent and could be prevented by the broad-spectrum caspase
      inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (zVAD-fmk). By
      contrast, no cytotoxicity was observed following the addition of methylglyoxal,
      acetaldehyde, formaldehyde, or 3-deoxyglucosone at concentrations found in
      peritoneal dialysis solutions. CONCLUSION: 3,4-DGE appears to be the main
      proapoptotic factor in high glucose peritoneal dialysis solutions. 3,4-DGE may
      impair peritoneal defenses by accelerating leukocyte apoptosis.

PMID- 16105066
TI  - Thrombosed arteriovenous fistula for hemodialysis access is characterized by a
      marked inflammatory activity.
AB  - BACKGROUND: Thrombosis is the dominant cause of failure of arteriovenous fistulas
      for hemodialysis access. Vascular inflammation, an important pathologic change in
      various human vascular diseases, may be involved in the thrombotic process of
      arteriovenous fistulas. METHODS: The inflammatory activities of 23 thrombosed and
      13 non-thrombosed stenotic arteriovenous fistulas were compared by investigating
      the contents of macrophages and lymphocytes, and the expression of intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor
      necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) using
      immunohistochemistry method. The expression of matrix metalloproteinase (MMP)-2
      and MMP-9, which play important roles in thrombosis of human coronary artery, was
      also investigated. The immunoreaction results were characterized using a
      semiquantitative scoring system. RESULTS: The macrophage and lymphocyte contents
      of the thrombosed group were abundant, and markedly greater than those of the non
      thrombosed group (P < 0.001 and P = 0.001, respectively). The infiltration of
      macrophages and neovasculature were spatially closely correlated. The expressions
      of VCAM-1, IL-6, and TNF-alpha, but not ICAM-1, were significantly higher in the
      thrombosed group (P = 0.031, P = 0.010, P < 0.001, and P= 1.000, respectively).
      The expression of MMP-2 was not different in either groups (P = 0. 344).
      Differential expression of MMP-9 by macrophages near the vascular lumen, but not
      those distant from the lumen, was observed in most thrombosed specimens.
      CONCLUSION: This study demonstrated that the thrombosed arteriovenous fistula was
      characterized by marked inflammation. We hypothesize that the preferential
      expression of MMP-9 at luminal edge may cause disruption of the anticoagulant
      endothelial barrier and contribute to luminal thrombosis of arteriovenous
      fistulas.

PMID- 16105067
TI  - Parameters derived by ultrasonic myocardial characterization in dialysis patients
      are associated with mortality.
AB  - BACKGROUND: Autopsy studies have shown that hypertrophic hearts of uremic
      patients have peculiar characteristics. Changes in tissue structure are
      detectable by ultrasound as changes in echo reflectivity. METHODS: We studied 96
      dialysis patients, 18 hypertensive subjects with normal renal function and 52
      healthy subjects. The echo pattern of interventricular septum was assessed by
      videodensitometry (VDT) (i.e., a computer-assisted quantitative analysis of gray
      levels). For each pixel a numerical value from 0 (black) to 255 (white) was
      assigned. From the resulting histogram of gray level frequency distribution, we
      obtained indexes of central tendency (reflectivity) and of homogeneity of
      distribution (uniformity). RESULTS: For the same septum thickness, dialysis
      patients showed a significantly greater reflectivity (87 +/- 19 and 70 +/- 17) (P
      < 0.001) and lower uniformity (137 +/- 32 and 184 +/- 71) (P < 0.007) compared
      with hypertensives. Hypertensive patients showed VDT parameters similar to
      control subjects in spite of significantly higher septum thickness (P < 0.003).
      Followed up after 5 years, dialysis patients with a reduced homogeneity of
      distribution of gray levels (lower uniformity) showed a significantly shorter
      survival (HR by Cox 2.5, 95% CI 1.21-5.27). CONCLUSION: For a similar degree of
      cardiac hypertrophy, dialysis patients differed widely from hypertensives in
      their VDT parameters. By contrast, the hypertensive heart differed from the
      normal heart in the degree of hypertrophy but not in terms of VDT parameters. VDT
      parameters are independent predictors of all-cause mortality in dialysis
      patients.

PMID- 16105068
TI  - Pyridoxamine improves functional, structural, and biochemical alterations of
      peritoneal membranes in uremic peritoneal dialysis rats.
AB  - BACKGROUND: We previously suggested that biochemical alterations of peritoneal
      membrane associated with long-term peritoneal dialysis might be, at least in
      part, accounted for by reactive carbonyl compounds overload originating both from
      uremic circulation and heat sterilization of glucose peritoneal dialysis fluid.
      In the present study, we utilized a uremic rat model on peritoneal dialysis and
      evaluated the protective effects of pyridoxamine, a recently developed inhibitor
      of advanced glycation end product (AGE), on structural, functional, and
      biochemical alterations of peritoneal membrane. METHODS: Uremic rats were
      generated by subtotal nephrectomy, some of which were undergone peritoneal
      dialysis with dialysate and/or given intraperitoneal pyridoxamine. Functional
      [dialysate/plasma ratio (D/P)(urea, creatinine), D/D(0 glucose)], structural
      (density of blood vessels in peritoneal membrane tissues), and molecular
      biochemical [formation of pentosidine, an AGE, by high-performance liquid
      chromatography (HPLC) assay and expressions of vascular endothelial growth factor
      (VEGF), and fibroblast growth factor 2 (FGF-2), by semiquantitative polymerase
      chain reaction (PCR) and/or immunohistochemistry] alterations of peritoneal
      membrane were assessed. RESULTS: Uremic peritoneal membrane was characterized by
      an increased functional area of exchange for small solutes between blood and
      dialysate, vascular proliferation, increased AGE genesis, and up-regulated
      expressions of angiogenic cytokines. The peritoneal membrane alterations
      associated with peritoneal dialysis are similar but more severe than those in
      uremia without peritoneal dialysis. Pyridoxamine given in uremic rats with
      peritoneal dialysis significantly improved functional and structural alterations.
      This improvement was accompanied by reduction of AGE accumulation and of
      angiogenic cytokines expressions. CONCLUSION: Peritoneal carbonyl stress derived
      from uremia as well as peritoneal dialysis procedure might contribute to the
      vascular proliferation through induction of bioactive molecules and to an
      increased functional area, eventually leading to ultrafiltration failure.
      Pyridoxamine may be beneficial in protection of uremic peritoneal membrane on
      peritoneal dialysis.

PMID- 16105069
TI  - Hemoglobin cycling in hemodialysis patients treated with recombinant human
      erythropoietin.
AB  - BACKGROUND: Treatment with recombinant human erythropoietin (rHuEPO) has been a
      major advance for the management of anemia in patients on hemodialysis. Therapy,
      however, is often observed to be associated with recurrent cyclic fluctuations in
      hemoglobin levels. The purpose of this analysis was to describe the phenomenology
      of hemoglobin cycling during rHuEPO treatment. METHODS: Data were analyzed for
      281 hemodialysis patients treated at Winthrop-University Hospital Dialysis
      Centers between 1998 and 2003. Eligible patients' first full 1-year period with
      less than 10 hospital days was studied. Hemoglobin cycling (cycles with amplitude
      >1.5 g/dL and duration >8 weeks) and excursions (half of one full cycle) were
      analyzed. RESULTS: Greater than 90% of patients experienced hemoglobin cycling.
      The mean number of hemoglobin excursions was 3.1 +/- 1.1 per patient/year. The
      mean amplitude per hemoglobin excursion was 2.51 +/- 0.89 g/dL. The mean duration
      of hemoglobin excursions was 10.3 +/- 5.1 weeks. Factors associated with
      initiation of up excursions included increases in rHuEPO dose (84%), intravenous
      iron treatment initiation or increase in dose (27%), posthospital discharge
      (36%), factors associated with down excursions included rHuEPO dose hold (15%) or
      dose reduction (62%), infection (6%), discontinuation of intravenous iron therapy
      (5%), and hospitalization (14%). Patients with frequent hemoglobin cycling (>two
      full cycles per year) were characterized as being more responsive to rHuEPO
      [index of EPO responsiveness (ERI) 1036 +/- 659 compared to 1992 +/- 701 for
      other patients] (P = 0.02). CONCLUSION: Hemoglobin cycling is a common occurrence
      in rHuEPO-treated hemodialysis patients. It is most closely associated with
      frequent rHuEPO dose changes, hospitalization, and iron treatment practices.

PMID- 16105070
TI  - The online measurement of hemodialysis dose (Kt): clinical outcome as a function
      of body surface area.
AB  - BACKGROUND: Recent advances enable the direct measurement of small molecule
      clearance, Kecn, during each dialysis. Average Kecn and treatment length, t, are
      multiplied giving total clearance, Kt. The body surface area (BSA) is a fixed
      transformation of height and weight and is a well recognized measure of body
      size. This project was conceived to search for clinical outcome-based functions
      for measured Kt in terms of BSA to enable simple Kt prescription guidelines for
      clinicians who are able to measure Kecn, and to provide foundations for future
      clinical research. METHODS: The data came from Fresenius Medical Care (NA) files
      and included more than 32,000 patients with height, weight, and paired Kecn and t
      measurements during December 2002. Measurements were averaged for the month and
      used as predictor measures in Cox models of survival time during 2003. Candidate
      Kt values from 30 L/treatment through 70 were examined to determine the best
      statistical fit for quintile and decile delimited BSA groups evaluating the best
      fit Kt treatment target for each group. Functional forms representing the
      relationship between target Kt values and mean BSA of the groups were then
      evaluated to determine the best fit. RESULTS: Kt targets increased with BSA in a
      curvilinear way such that the rate of increase is greater at low BSA than high.
      The best statistical fit was a double reciprocal form, Kt = 1/(a + b/BSA); "a"
      and "b" are statistically derived coefficients. The form has an appealing
      mathematical property; Kt approaches 0 as BSA approaches 0. Other forms fit the
      data nearly as well, however, and can be used to estimate Kt targets for patients
      with different BSA. CONCLUSION: Empirical, outcome-based functions of measured Kt
      in terms of BSA exist and can be used as aids for prescribing and judging
      hemodialysis treatment.

PMID- 16105071
TI  - Adrenomedullin reflects cardiac dysfunction, excessive blood volume, and
      inflammation in hemodialysis patients.
AB  - BACKGROUND: Plasma adrenomedullin (AM) reflects cardiac dysfunction and predicts
      survival after myocardial infarction. The present study was designed to
      investigate whether the mature AM (mAM) reflects status of cardiac function,
      systemic blood volume, or inflammation in hemodialysis patients with
      cardiovascular disease, and whether mortality and additional cardiovascular
      morbidity can be predicted by mAM. METHODS: Plasma levels of mAM, atrial
      natriuretic peptide (ANP), B-type natriuretic peptide (BNP), norepinephrine (NE),
      and C-reactive protein (CRP) before hemodialysis were measured in 67 chronic
      hemodialysis patients with cardiovascular disease, along with 2-dimensional and
      Doppler echocardiographic variables. RESULTS: By univariate regression analysis,
      mAM correlated negatively with pulmonary venous flow velocity ratio and left
      ventricular (LV) ejection fraction and positively with LV inflow velocity ratio,
      LV end-diastolic, end-systolic volume indexes, plasma CRP level, and removal
      fluid volume by ultrafiltration. Multivariate stepwise regression analysis
      revealed that mAM reflected all variables better than log [ANP], log [BNP], and
      log [NE]. During a 1-year follow-up period, 7 patients died and 8 had additional
      cardiovascular events. Event-free Kaplan-Meier curves based on the median mAM
      (4.55 pmol/L) showed that patients with high plasma mAM levels had higher
      mortality and morbidity than those with low plasma mAM levels (P = 0.0056). By
      Cox multivariate proportional hazard analysis, mAM was related to mortality and
      morbidity [hazard ratio (HR) 4.55, 95% CI 1.2-16.8, P= 0.023). CONCLUSION: Plasma
      mAM reflects cardiac dysfunction, excessive blood volume, and inflammation better
      than ANP, BNP, and NE, resulting in a predictor of mortality and cardiovascular
      morbidity in hemodialysis patients with cardiovascular disease.

PMID- 16105072
TI  - Racial and ethnic disparities in renal disease.

PMID- 16105073
TI  - Renewal of FSP1: a marker of fibrogenesis on human renal biopsies.

PMID- 16105075
TI  - Changes in the composition of carnitines in hemodialysis patients.

PMID- 16105076
TI  - Albuminuria in patients with hepatitis C: is inflammation the missing link?

PMID- 16105077
TI  - Red blood cell deformability and diabetic nephropathy.

PMID- 16105079
TI  - Postprocedural drop in hematocrit versus contrast-induced nephropathy: eggs or
      chickens?

PMID- 16105081
TI  - PAI-1 in diabetic nephropathy.

PMID- 16105083
TI  - Does fluvastatin really have an antioxidant effect in humans?

PMID- 16105085
TI  - C-reactive protein and coronary heart disease in hemodialyzed patients.

PMID- 16105086
TI  - Combination therapy with ACE inhibitors and angiotensin II receptor blockers in
      chronic renal disease: new therapeutic world beyond blood pressure reduction.

PMID- 16105087
TI  - Emerging treatment approaches for the systemic amyloidoses.

PMID- 16105088
TI  - Apoptosis in the epithelial cells of the rests of Malassez of the periodontium of
      rat molars.
AB  - BACKGROUND AND OBJECTIVES: Epithelial rests of Malassez are clusters of cells
      derived from Hertwig's root sheath that remain in the periodontal ligament
      throughout life. Although it is known that the cells of Malassez proliferate,
      there are no studies showing that they undergo programmed cell death, i.e.
      apoptosis. In most tissues, proliferation is balanced by apoptosis. Thus we
      examined regions of the periodontium of young and adult rat molars in the hope of
      detecting apoptosis. METHODS: Wistar rats aged 29, 45 and 120 days were killed
      with chloral hydrate (600 mg/kg). Fragments containing maxillary molars were
      removed and fixed in formaldehyde, decalcified, and embedded in paraffin and
      glycol methacrylate. Sections were stained with hematoxylin/eosin and the
      Terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labeling (TUNEL)
      method for detection of apoptosis. Specimens were also fixed in glutaraldehyde
      formaldehyde, decalcified and processed for transmission electron microscopy.
      RESULTS: Epithelial rests of Malassez containing round/ovoid basophilic dense
      bodies and TUNEL-positive structures were found in all specimens examined.
      Ultrastructural examination revealed that some cells of Malassez contained masses
      of condensed peripheral chromatin and a shrunken cytoplasm exhibiting intact
      organelles--images typical of apoptosis. Moreover, round/ovoid electron-opaque
      structures appeared to be in the process of being engulfed by neighboring
      epithelial cells of Malassez. CONCLUSIONS: Our results demonstrate that
      epithelial cells of Malassez's rests undergo apoptosis in the developing and
      adult periodontium. Apoptosis may, together with proliferation, be part of the
      mechanism of turnover/remodelling of the cells of Malassez.

PMID- 16105089
TI  - A synergistic chlorhexidine/chitosan combination for improved antiplaque
      strategies.
AB  - BACKGROUND: The minor efficacy of chlorhexidine (CHX) on other cariogenic
      bacteria than mutans streptococci such as Streptococcus sanguinis may contribute
      to uneffective antiplaque strategies. METHODS AND RESULTS: In addition to CHX
      (0.1%) as positive control and saline as negative control, two chitosan
      derivatives (0.2%) and their CHX combinations were applied to planktonic and
      attached sanguinis streptococci for 2 min. In a preclinical biofilm model, the
      bacteria suspended in human sterile saliva were allowed to attach to human enamel
      slides for 60 min under flow conditions mimicking human salivation. The efficacy
      of the test agents on streptococci was screened by the following parameters:
      vitality status, colony-forming units (CFU)/ml and cell density on enamel. The
      first combination reduced the bacterial vitality to approximately 0% and yielded
      a strong CFU reduction of 2-3 log(10) units, much stronger than CHX alone.
      Furthermore, the first chitosan derivative showed a significant decrease of the
      surface coverage with these treated streptococci after attachment to enamel.
      CONCLUSIONS: Based on these results, a new CHX formulation would be beneficial
      unifying the bioadhesive properties of chitosan with the antibacterial activity
      of CHX synergistically resulting in a superior antiplaque effect than CHX alone.

PMID- 16105090
TI  - Lipid peroxidation: a possible role in the induction and progression of chronic
      periodontitis.
AB  - OBJECTIVES: Reactive oxygen species (ROS) are implicated in the destruction of
      the periodontium during inflammatory periodontal diseases. The imbalance in
      oxidant/antioxidant activity may be a key factor in the damaging effects of ROS.
      This study aimed to determine the lipid peroxidation levels in gingival
      crevicular fluid and saliva, and glutathione (GSH) and glutathione peroxidase
      (GPx) in saliva in patients with chronic periodontitis. METHODS: Gingival
      crevicular fluid and saliva were collected from 13 patients and 9 healthy control
      subjects during the preliminary study, and from 21 patients during the subsequent
      study. Lipid peroxidation level, GSH level and GPx activity were determined by
      spectrophotometric assay. RESULTS: The preliminary study found that when
      comparing patients to healthy controls, the gingival crevicular fluid samples
      produced the following results, respectively: higher lipid peroxidation
      concentration (microm) (by sites: 167.55 vs. 53.71, p < 0.0001; by subjects:
      151.99 vs. 50.66, p < 0.005) and total amount (pmol) (by sites: 93.02 vs. 8.47, p
      < 0.0001, by subjects: 80.44 vs. 7.84, p < 0.0005). In saliva samples, lower GSH
      concentration (microm) (373.04 vs. 606.67, p < 0.05), higher lipid peroxidation
      concentration (microm) (0.66 vs. 0.13, p < 0.0005), and no difference in GPx
      activity were found in patients than in those of healthy controls. The subsequent
      study showed statistically significant (p < 0.05) improvement of clinical
      periodontal parameters (plaque index, gingival index, probing attachment level,
      probing pocket depth and gingival crevicular fluid volume), decreases in gingival
      crevicular fluid lipid peroxidation levels (concentration and total amount) at
      the sites after the completion of phase 1 periodontal treatment. Similarly, the
      periodontal treatment resulted in a significant decrease of lipid peroxidation
      concentrations (p < 0.05), increase in GSH concentration (p < 0.001), and no
      change in GPx activity in saliva samples. CONCLUSION: The increased levels of
      lipid peroxidation may play a role in the inflammation and destruction of the
      periodontium in periodontitis.

PMID- 16105091
TI  - The effect of Emdogain on ectopic bone formation in tubes of rat demineralized
      dentin matrix.
AB  - BACKGROUND: Emdogain (EMD) is made from enamel matrix proteins (EMPs) from the
      tooth germ of swine and propylene glycol alginate (PGA) as a matrix. The function
      of EMD is known to differentiate cells of the dental follicle into cementoblasts.
      However, little is known about the effect of EMD on mesenchymal cells in other
      tissue. OBJECTIVE: The purpose of this study was to investigate whether EMD has
      the ability to induce hard tissue when applied with or without demineralized
      dentin matrix. METHODS: Half of the dentin tubes prepared from rat incisors were
      demineralized by treatment with 0.6 N hydrochloric acid for 3 h. EMD or PGA was
      injected into the demineralized or non-demineralized dentin tubes, which were
      then transplanted into rectus abdominis muscles. Untreated dentin tubes were also
      transplanted as a control. Animals were killed at 7, 14 and 21 days after the
      implantation. RESULTS: Non-demineralized dentin tubes with or without EMD or PGA
      did not form any hard tissue. In the demineralized group, chondrogenesis in the
      PGA groups occurred earlier than in the EMD groups. The expression of vascular
      endothelial growth factor (VEGF) mRNA in the demineralized group with PGA at day
      14 was the highest. The expression of osteopontin and osteocalcin mRNAs was
      higher in all groups at 21 days compared with 7 or 14 days. CONCLUSION: These
      results suggest that neither EMD nor PGA has the ability to induce hard tissue
      and that EMPs contained within EMD might aggregate on the dentin surface and
      inhibit the effect of the demineralized dentin matrix.

PMID- 16105092
TI  - The gingival crevicular fluid ciprofloxacin level in subjects with gingivitis and
      periodontitis, and its effects on clinical parameters.
AB  - OBJECTIVES: The purpose of this study, conducted on patients with gingivitis and
      periodontitis, was twofold: to find out the serum and gingival crevicular fluid
      concentration of ciprofloxacin, which is a common drug used effectively against
      Actinobacillus actinomycetemcomitans and to determine the effects of
      ciprofloxacin administration on clinical parameters. METHOD: A total of 32 adult
      patients, consisting of 16 subjects with gingivitis and 16 subjects with
      untreated chronic periodontitis, were included in the study. The subjects were
      divided into four groups: group I included eight subjects with chronic gingivitis
      who had not previously received any ciprofloxacin; group II included eight
      subjects with chronic gingivitis to whom three doses of ciprofloxacin were
      administered (Siprosan 500 mg) to establish adequate gingival crevicular fluid
      and serum concentrations of the agent; group III consisted of eight subjects with
      chronic periodontitis who had not received any ciprofloxacin; group IV included
      eight subjects with chronic periodontitis to whom three doses of ciprofloxacin
      were administered to establish adequate gingival crevicular fluid and serum
      concentrations of the agent. All patients were systemically healthy, free of pain
      and reported no current medication usage. Each patient was treated with scaling
      and/or root planing using specific hand instruments under local anesthesia.
      Gingival index, plaque index and clinical attachment levels of the teeth were
      used to determine the clinical condition of the subjects and findings were
      recorded at the beginning, seventh day, 21st day and third month of the study.
      Serum ciprofloxacin level was measured in venous blood. Approximately 5 ml of
      venous blood was drawn from subjects in groups II and IV using a standard
      venipuncture technique. Gingival crevicular fluid samples were sampled from six
      interproximal sites with six paper strips in the posterior region of upper jaw
      (excluding third molar) and all gingival crevicular fluid and serum samples were
      evaluated by high-performance liquid chromatography. RESULTS: The serum
      concentrations of ciprofloxacin at the first and 72nd hour were not significantly
      different in subjects with periodontitis compared to subjects with gingivitis.
      But the gingival crevicular fluid concentrations of ciprofloxacin at the same
      hours were significantly high in subjects with periodontitis compared to subjects
      with gingivitis. Both subjects with gingivitis and periodontitis had
      significantly higher ciprofloxacin levels in the gingival crevicular fluid than
      in serum. The application of ciprofloxacin did not have any positive or
      statistically significant effect upon the clinical parameters of the subjects
      with gingivitis. On the other hand, a significant decrease in the clinical
      attachment level scores of the subjects with periodontitis (group IV) was
      observed compared to group III in the 21st day and third month. CONCLUSION:
      According to these results, the use of ciprofloxacin as an alternative drug in
      subjects with periodontitis but not gingivitis can be recommended. However, long
      term studies are also needed to assess the effects of ciprofloxacin on clinical
      parameters.

PMID- 16105093
TI  - Differential effects of estrogen on DNA synthesis in human periodontal ligament
      and breast cancer cells.
AB  - BACKGROUND: It is important to clarify the biological function of the female sex
      hormones estrogen and progesterone in periodontal ligament cells, as these
      hormones may affect periodontal health. We have previously shown that human
      periodontal ligament cells express estrogen receptor beta (ERbeta) but not
      ERalpha, whereas human breast cancer cells (MCF7) express both ERalpha and
      ERbeta. Data on progesterone receptor (PgR) expression in human periodontal
      ligament cells have not been reported. OBJECTIVES: Determine PgR expression in
      human periodontal ligament and MCF7 cells and to investigate how estrogen affects
      DNA and collagen synthesis in these two cell types showing different pattern of
      expression for ERalpha and beta. METHODS: Periodontal ligament cells were
      obtained from the periodontal ligament of premolars extracted for orthodontic
      reasons and MCF7 cells from the American Type Culture Collection (ATCC). PgR
      expression was determined by immunocytochemistry. DNA and collagen synthesis was
      determined by [(3)H]thymidine and L-[(3)H]proline incorporation, respectively.
      RESULTS: PgR immunoreactivity was observed in nuclei of MCF7 but not periodontal
      ligament cells. Treatment with estrogen (17beta-estradiol, E(2)) at physiological
      concentrations for 24 h stimulated DNA synthesis by more than two times in MCF7
      cells, whereas there was no effect on periodontal ligament cell DNA synthesis.
      The ER blocker ICI 182780 fully reversed the stimulatory effect of E(2). Not only
      short-term (24 h) but also long-term (5 days) treatment with E(2) lacked effect
      on DNA synthesis in periodontal ligament cells. Neither periodontal ligament cell
      viability nor collagen synthesis was affected by E(2) treatment. Identical
      results were observed in periodontal ligament cells from male and female
      subjects. CONCLUSIONS: Human MCF7 but not periodontal ligament cells express PgR,
      suggesting that progesterone via PgR affects MCF7 but not periodontal ligament
      cells. Further, estrogen stimulates breast cancer MCF7 cell proliferation,
      whereas it has no effect on proliferation of periodontal ligament cells, probably
      reflecting cell type specific ER expression pattern in these two cell types.

PMID- 16105094
TI  - Lipopolysaccharide-binding protein down-regulates the expression of interleukin-6
      by human gingival fibroblast.
AB  - BACKGROUND: Lipopolysaccharide-binding protein (LBP) participates in the
      interaction of lipopolysacchaide (LPS) with CD14 to modulate the expression of
      cytokines. Human gingival fibroblast may actively participate in LPS-induced
      immuno-inflammatory responses through CD14, toll-like receptor (TLR) superfamily,
      MD-2 and related adaptive proteins, leading to the expression of cytokines.
      OBJECTIVES: The present in vitro study aimed to investigate the possible effect
      of LBP and E. coli LPS interaction on the expression of cellular LPS receptors
      and IL-6 by human gingival fibroblast. METHODS: The mRNA expression of CD14, LBP,
      TLR-2, TLR-4, MD-2 and IL-6 in human gingival fibroblast explants was detected by
      reverse transcriptionpolymerase chain reaction (RT-PCR) in the presence or
      absence of E. coli LPS and recombinant human LBP (rhLBP), while IL-6 peptides
      were analyzed by ELISA and immunohistochemistry, respectively. RESULTS: Human
      gingival fibroblast could constitutively express CD14, MD-2 and IL-6 mRNAs, but
      not TLR-2, TLR-4 and LBP mRNAs. E. coli LPS induced the messages expression of MD
      2, TLR-2 and -4. The expression of both IL-6 message and peptide was up-regulated
      by E. coli LPS in a dose dependent manner. Whereas rhLBP could significantly down
      regulate the expression of both mRNAs and peptides of CD14 and IL-6 but not MD-2
      signals in the presence or absence of E. coli LPS. The up-regulated expression of
      TLR-2 and -4 by E. coli LPS no longer existed in the presence of rhLBP.
      CONCLUSIONS: This study suggests that LBP may down-regulate the expression of IL
      6 by human gingival fibroblast. Further studies are warranted to clarify the
      molecular mechanisms of LBP in regulation of cytokine expression by host cells
      and to elaborate the relevant clinical implications.

PMID- 16105095
TI  - Production of osteopontin by cultured porcine epithelial cell rests of Malassez.
AB  - BACKGROUND: The epithelial cell rests of Malassez (ERM) are derived from
      Hertwig's epithelial root sheath (HERS). During development the cells of HERS
      deposit a variety of molecules on the newly forming root surface. The possibility
      that ERM retain this potential after root development is completed and secrete
      bone or cementum-related proteins needs to be investigated. The purpose of this
      study was to determine the expression of the non-collagenous proteins osteopontin
      (OPN) and bone sialoprotein (BSP) by cells derived from the epithelial cell rests
      of porcine periodontium. METHODS: ERM and fibroblasts were cultured from porcine
      periodontal ligament. The cells were identified and characterized using
      transmission electron microscopy, immunohistochemistry, western blot analysis of
      proteins, reverse transcription-polymerase chain reaction and ability to form
      mineralized nodules in culture. In particular the expression of the mineralized
      tissue-related proteins, BSP and OPN, was studied. RESULTS: Cells from porcine
      periodontal ligaments were successfully cultured; separated and characterized as
      being of either an epithelial or fibroblastic phenotype. Although the ERM did not
      form mineralized nodules in culture, they did express a significant amount of
      mRNA for OPN. CONCLUSION: The results from this study provide evidence that ERM
      express mRNA for at least one bone/cementum-related protein. Whether this
      function would be consistent with a role for ERM in tissue formation,
      inflammation and regeneration remains to be established.

PMID- 16105096
TI  - Anti-tumor antibodies in ovarian cancer.
AB  - Anti-tumor antibodies have potential as cancer biomarkers. There is relatively
      limited identification of anti-tumor antibodies in response to ovarian cancer,
      compared with studies for other cancers. There is also very limited information
      on the prevalence of anti-tumor antibodies among ovarian cancer patients.
      Although most anti-tumor antibodies react with antigens common to both tumor and
      normal tissue, the anti-tumor response tends to be confined to individuals with
      ovarian cancer, similar to other cancers. Antibodies to HOXA7, a differentiation
      antigen, have the highest reported prevalence in ovarian cancer (67%). Antibodies
      to other ubiquitous antigens including NY-ESO-1, Ep-CAM (epithelial cell adhesion
      molecule), HSP-90 (heat shock protein 90), and mutated p53 have been identified
      in ovarian cancer. Anti-tumor antibody specificity reflects the heterogeneity of
      antigen expression in tumors. Tests based on panels of a combination of anti
      tumor antibodies may be more predictive for ovarian cancer, as no single
      specificity accounts for ovarian tumors. In addition to characterization of anti
      tumor antibodies as diagnostic markers, study of anti-tumor antibodies is likely
      to provide insights into mechanisms of tumor development. There is evidence of
      antibodies to tumor antigens and of activated T cells, suggesting immune
      recognition of tumor antigens occurred. Nonetheless, as tumors are not
      'rejected', it is likely that there are alterations in the immune system. The
      basis for tumor growth in the face of immune activity remains to be determined.

PMID- 16105097
TI  - Mothers in stress: consequences for the offspring.
AB  - No memories exist on one's time before birth. However, this does not imply that
      the developing fetus is not susceptible to external impulses. On the contrary,
      the fetus is extremely vulnerable e.g. to environmental challenges, and a wealth
      of data reveals that conditions in utero affect the health of the fetus before
      and after birth. Threats for the growing fetus include psychological challenges
      perceived by the mother, e.g. high levels of stress during pregnancy. However,
      stress experienced during pregnancy not only leads to pregnancy complications
      like miscarriage, pre-eclampsia, preterm parturition, low birth weight or major
      congenital malformations, stress also increases the risk of the child to develop
      diseases in the subsequent periods of life. This condition is termed fetal
      programming of adult disease. Programming agents seem to include growth factors,
      cytokines and hormones, all of which can be altered by stress. As a consequence,
      such 'stress-modified' systems of the offspring are more susceptible to
      environmental influences during later life, e.g. the development of atopic
      diseases upon exposure to antigens. The present review illuminates the complexity
      of stress perception on fetal programming focusing predominately on the onset of
      atopic diseases on the background of published evidence from immunology,
      endocrinology, neurobiology and neonatology.

PMID- 16105098
TI  - Decreased proinflammatory cytokines in cervicovaginal fluid, as measured in
      midgestation, are associated with preterm delivery.
AB  - PROBLEM: The main aim of this study was to investigate the relationship between
      selected proinflammatory cytokines [interleukin IL-1 alpha (IL-1alpha), IL-1 beta
      (IL-1beta), IL-6 and IL-8] concentrations in cervicovaginal fluid, as measured in
      midgestation, and the risk of subsequent preterm delivery. METHOD OF STUDY:
      Cervicovaginal fluids were obtained from a cohort of 114 pregnant women at 22-34
      weeks' gestation and analyzed for the concentrations of IL-1alpha, IL-1beta, IL-6
      and IL-8 using enzyme-linked immunosorbent assay technique. Lower genital tract
      microbiology was diagnosed using Gram stain method and by culture. RESULTS: Mean
      gestational age at the time of sampling was 29.0 weeks. Mean time between
      sampling and delivery was 9.3 weeks (S.D. 4.7). Median cervicovaginal
      concentrations of IL-1alpha, IL-1beta, IL-6 and IL-8 did not differ between
      preterm and term delivery group. Women with lower genital tract pathological
      flora and IL-1alpha concentration below 25th percentile presented significant
      risk of subsequent preterm delivery as compared with women with no low cytokines
      (OR = 10.7; 95% CI, 2.0-58.1). Women with more than one cytokine' low
      concentration (below 25th percentile) presented an increased risk of preterm
      delivery--OR = 11.8 (95% CI, 1.8-78.0). CONCLUSIONS: The midgestation cytokines'
      measurement in cervicovaginal fluid of pregnant women could be useful for
      prediction of preterm delivery only among women with lower genital tract
      pathological flora.

PMID- 16105099
TI  - Serum levels of macrophage colony stimulating, vascular endothelial, and placenta
      growth factor in relation to later clinical onset of pre-eclampsia and a small
      for-gestational age birth.
AB  - PROBLEM: The multisystem disorder of pre-eclampsia (PE) becomes manifest in late
      gestation, but the pathology originates in early pregnancy by the deleterious
      action of placental substances to the maternal endothelial system. These factors
      were searched for in the attempt to identify, as early as possible, the
      pregnancies with an increased risk of developing pre-eclampsia. The literature is
      equivocal regarding the usefulness of various markers including vascular
      endothelial growth factor (VEGF) and macrophage colony-stimulating factor (M
      CSF). Results are often confounded by a varying fraction of pregnancies affected
      by foetal growth restriction (FGR) amongst the case and control groups. METHOD OF
      STUDY: In a nested case-control study we compared the serum levels of M-CSF,
      VEGF, and placenta growth factor (PLGF) in 23 pregnancies with subsequent mild PE
      without FGR and nine FGR pregnancies without PE with 40 matched controls at 17,
      25, and 33 weeks of gestation cross-sectionally and longitudinally. RESULTS: VEGF
      levels were reduced in FGR but not in subsequently pre-eclamptic pregnancies at
      17, 25, and 33 weeks. In contrast, PLGF was reduced in the PE but not in the FGR
      group. M-CSF did not differ between the three groups. CONCLUSION: Depending on
      which growth factor is found to be reduced, an early distinction can be made in
      terms of an increased risk for PE or FGR. Inconsistencies in the literature may
      reflect differences in PE disease severity between studies and the presence of a
      varying fraction of cases with FGR.

PMID- 16105100
TI  - The skewed TCR-BV repertoire displayed at the maternal-fetal interface of women
      with unexplained pregnancy loss.
AB  - PROBLEM: The study was undertaken to investigate T-cell receptor (TCR) variable
      beta (BV)-chain usage at maternal-fetal interface and explore the relationship
      between the skewed TCR-BV usage and unexplained pregnancy losses. METHOD OF
      STUDY: A total of 57 patients with unexplained pregnancy loss including 39 cases
      with unexplained spontaneous abortion and 18 cases with unexplained recurrent
      spontaneous abortion (RSA) were chosen in Renji Hospital, Shanghai Second Medical
      University matched with 41 women with normal pregnancies in first trimester
      between September 2002 and November 2003. A high-resolution spectratyping
      analysis of complementarity-determining region 3 (CDR3) was used to detect and
      compare the degree and pattern of TCR-BV repertoire usage at the maternal-fetal
      interface between patients with pregnancy loss and normal controls. RESULTS:
      There were two comparisons of TCR usage performed between patients and controls,
      which included the degree (mean value of every TCR-BVn expression) and the
      pattern (skewed TCR-BVn frequency). The skewed TCR-BVn is defined as an absolute
      BVn usage of > 5% calculated from the formula or a double increased BVn usage
      compared with the mean value of normal BVn. According to the degree of TCR-BV
      usage, BV2 (P = 0.046), BV10 (P = 0.016), and BV11 (P = 0.030) in spontaneous
      abortion group and BV19 (P = 0.038) in RSA group showed higher usage, while BV5.2
      (P = 0.006 and P = 0.046) in both abortion groups showed significantly lower
      usage when compared with normal controls. About the pattern of skewed TCR-BV
      distribution, we found that TCR-BV2, -3, -6, and -7 were the four most common BV
      families in deciduas of patients with both types of abortion and normal controls.
      Women with spontaneous abortion demonstrated higher frequency of BV10 (P = 0.035)
      and lower frequencies of BV4 (P = 0.002) and BV5.2 (P = 0.003) in comparison with
      controls. In RSA, higher frequencies of BV15 (P = 0.018), BV19 (P = 0.049), and
      BV20 (P = 0.018), in the mean time, lower frequencies of BV4 (P = 0.026) and BV7
      (P = 0.018) distributions were verified. CONCLUSIONS: Our results suggested that
      a significant skewed TCR-BV repertoire occurred at the maternal-fetal interface
      with patients undergoing abortion. The specific skewed usages of TCR-BV might be
      associated with the susceptibility to unexplained pregnancy loss.

PMID- 16105101
TI  - Type 2 11beta-hydroxysteroid dehydrogenase activity in human fallopian tube and
      correlation of enzyme levels with endometrial histopathology.
AB  - PROBLEM: The inter-conversion of hormonally active cortisol and inactive
      cortisone is catalyzed by 11beta-hydroxysteroid dehydrogenase (11beta-HSD). This
      conversion controls the level of active glucocorticoid concentration in tissues.
      As the fallopian tube plays a major role in the process of fertilization, we
      wanted to investigate whether 11beta-HSD is present in the human fallopian tube
      to control the glucocorticoid levels as in other tissues. METHOD OF STUDY:
      Isthmic, ampullary and fimbrial portions of the fallopian tube are obtained from
      patients undergoing hysterectomy and salpingo-oopherectomy for symptomatic
      leomyomata uteri. 11beta-HSD activities were measured in the homogenates of the
      tube, cortisol as the steroid substrate. The enzyme activity was expressed as
      nanomolar cortisone formed per minute per gram of tissue (mean +/- S.D.).
      RESULTS: A significant level of 11beta-HSD activity in oxidation direction was
      found in all three parts of the tube. There is no significant difference in the
      distribution of the enzyme activity throughout the tube. When tubal 11beta-HSD
      activity was compared with endometrial histology, the enzyme activity is
      significantly lower in proliferative endometrium when compared with secretory
      endometrium (P = 0.002). The enzyme activity in inactive endometrium is
      significantly higher than the active endometrium (P = 0.05). CONCLUSION: The
      presence of 11beta-HSD throughout the fallopian tube and its correlation to
      endometrial histology is indicative of its probable role in controlling the
      glucocorticoid levels in the tissue, which in turn may influence the
      fertilization process.

PMID- 16105102
TI  - Altered immunophenotypic parameters in infertile women. Possible role of herpes
      viremia.
AB  - PROBLEM: Purpose of this study was to reveal any alteration in peripheral blood
      lymphocytic concentrations of a large cohort of infertile women and to
      investigate the possible role of herpes viremia in the peripheral
      immunostimulation. METHOD OF STUDY: The immunophenotypic characteristics and the
      presence of herpes viruses DNA in the peripheral blood of 168 infertile women
      were studied. RESULTS: Peripheral CD56+/CD16+ natural killer (NK) cell
      concentration, CD56+/CD16- NK cell concentration, white blood cell (WBC)
      concentration and lymphocyte concentration were statistically correlated to
      herpes viremia. Epstein-Barr virus (EBV) viremia is related with a limited
      reduction of CD56+/CD16- cell levels in the peripheral blood of infertile women
      with regard to the rest of herpes viruses. High T-lymphocyte concentration, CD4+
      T-cell concentration and CD8+ T-cell concentration was observed in women positive
      for three different kinds of herpes viruses (triple viremia) in the peripheral
      blood. CONCLUSIONS: Assuming that all women under study remained asymptomatic,
      these data suggest that subclinical herpesvirus viremia may be an important cause
      of peripheral immunostimulation in women with a history of infertility.

PMID- 16105103
TI  - Anti-phospholipid antibodies against phosphatidylinositol, and phosphatidylserine
      are more significant in reproductive failure than antibodies against cardiolipin
      only.
AB  - PROBLEM: The humoral immune response to phospholipids was investigated in women
      with reproductive failure [1073 women after one in vitro fertilization (IVF), 853
      women after two and more IVF, 627 women after three and more repeated spontaneous
      miscarriages or missed abortions, 412 women after diagnostic laparoscopy] and
      compared with that of 391 healthy fertile women. METHOD OF STUDY: Sera from all
      women in the study were tested by enzyme-linked immunosorbent assay (ELISA) for
      the detection of IgG, IgA, and IgM isotypes of antibodies against seven
      phospholipids (aPLs), i.e. cardiolipin, L-phosphatidylserine,
      phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine,
      phosphatidylacid as well as against beta2-glycoprotein I. RESULTS: Patients after
      two and more IVF (48 and 50%, respectively), patients with three and more
      repeated spontaneous miscarriages (50 and 46.5%, respectively) are associated
      with significantly higher serum levels of aPLs against inositol, and L-serine (P
      < 0.01). A quarter of them were positive for three and more aPLs. CONCLUSION: It
      seems that determination of aPLs only against cardiolipin in reproductive failure
      is not sufficient for obstetric-gynecology diagnosis as the primary anti
      phospholipid syndrome. Our long-ranging study (from 1998 to 2003) shows the
      necessity to test for a complete aPLs profile. Sera from patients after two and
      more IVF procedures, and sera from women after three and more repeated abortions
      are immunologically more active than sera from women after one unsuccessful IVF
      and sera from women after diagnostic laparoscopy. This important result is very
      significant for future treatment.

PMID- 16105114
TI  - Eating after mild pancreatitis.

PMID- 16105115
TI  - Secondary myelodysplastic syndrome after small cell lung cancer and esophageal
      cancer.
AB  - A 50-year-old man was referred to our department with esophageal cancer. He had
      past history of small cell lung cancer treated with chemoradiation therapy 10
      years prior. The disease was evaluated as complete remission after chemoradiation
      therapy and no recurrence had been observed. Esophagectomy accompanying
      postoperative chemotherapy was applied, but he died of secondary myelodysplastic
      syndrome with its acute myeloblastic transformation. Risk evaluation revealed a
      high incidence of esophageal cancer after radiation therapy and hematological
      malignancies after chemoradiation therapy in usual regimen with topoisomerase
      inhibitor or alkylating agents. Chemoradiation therapy is thought to be one of a
      few highly effective therapeutic alternatives and many complete remission cases
      have been reported in small cell lung cancer or esophageal cancer. In post
      therapeutic follow up of patients with such past therapeutic histories, we should
      be cautious about secondary malignancies even if primary malignant disease was
      evaluated as complete remission in long past history.

PMID- 16105116
TI  - Jaundice in malaria.
AB  - Jaundice is not an unusual accompaniment of malaria. It can occur due to
      intravascular hemolysis, disseminated intravascular coagulation, and, rarely,
      'malarial hepatitis'. Although the primary schizogony of the malarial parasite
      always leads to the rupture of the infected hepatocyte, alteration of the hepatic
      functions is uncommonly recorded due to this event. Histologically, the hepatitis
      or the actual inflammation in the liver has never been demonstrated. Nonetheless,
      the term 'malarial hepatitis' (MH) has been used in the literature to describe
      the occurrence of hepatocellular jaundice in patients with Plasmodium falciparum
      infection. The authors' own data and review of the literature indicate that it is
      not an uncommon entity. In endemic areas, jaundice is seen in approximately 2.5%
      of patients with falciparum malaria. It also appears to be a heterogeneous
      syndrome and one can recognize two clinical subsets. In one group there was an
      acute, virulent presentation with coma, renal failure and in some cases even
      hemorrhagic manifestations. It is only in this setting that jaundice signified a
      'severe' disease as noted by the World Health Organization action program. This
      presentation is often confused with acute viral hepatitis and acute hepatic
      failure in non-endemic areas, but can be clinically differentiated.

PMID- 16105117
TI  - Prevalence of gastric cancer decreases with age in long-living elderly in Japan,
      possibly due to changes in Helicobacter pylori infection status.
AB  - OBJECTIVES: The prevalence of Helicobacter pylori (Hp) infection and the
      development of gastric cancer are both believed to increase with age in Japan.
      However, no studies have investigated people older than 65 years in detail. In
      this study, we investigated the prevalence of Hp infection and gastric cancer in
      the elderly, and analyzed the influence of both factors on longevity. METHODS:
      All patients investigated were 65 years old and over. A total of 1877 autopsy
      cases were used to investigate the prevalence of gastric cancer and colonic
      cancer. Serum samples were obtained from 644 patients with dyspepsia and analyzed
      for Hp-IgG antibodies. Of these 644 patients, 63 underwent upper gastrointestinal
      endoscopies. Five biopsies were obtained and evaluated for the following
      morphological variables: neutrophils, mononuclear cell, atrophy, and intestinal
      metaplasia. Hp infection was evaluated histologically and with the (13)C-urea
      breath test. RESULTS: The prevalence of gastric cancer was significantly lower in
      subjects older than 85 years. The positive rate of serum Hp-IgG, and Hp infection
      as detected histologically and by the (13)C-urea breath test, also decreased with
      age. In Hp(+) patients, the neutrophil score significantly decreased with age. In
      Hp(-) patients, however, the intestinal metaplasia score significantly increased
      with age. CONCLUSIONS: The non-infection of Hp itself is not related to longevity
      in Japanese elderly, because even Hp(-) patients appear to have been infected
      previously with Hp. The lower prevalence of gastric cancer in the elderly may be
      due to the disappearance of Hp colonization, which may contribute to longevity in
      Japanese elderly.

PMID- 16105118
TI  - Selective reduction of anti-Helicobacter pylori IgG subclass antibody in gastric
      carcinoma.
AB  - BACKGROUND: Epidemiological studies have demonstrated strong links between
      Helicobacter pylori infection and gastric adenocarcinoma. Recent studies suggest
      that cell-mediated immunity influences the outcome of infection, including the
      development of gastric adenocarcinoma. The T-cell response can be characterized
      in terms of the secreted cytokine profile, which in turn influences the B-cell
      response including the balance of IgG subclass antibody. METHODS: Serum anti-H.
      pylori IgG, IgG1 and IgG2 antibodies were studied by ELISA in subjects with
      benign gastric diseases, gastric dysplasia and gastric adenocarcinoma. RESULTS:
      The distribution patterns of IgG subclass anti-H. pylori antibody varies
      significantly between H. pylori-linked benign and malignant disease in subjects
      infected with H. pylori. Significantly lower IgG2 levels were found in subjects
      with gastric adenocarcinoma compared with those with reflux esophagitis, chronic
      gastritis, gastric ulcer, and peptic ulcer, while IgG1 antibody remained at
      similar levels in both benign and malignant disease. A limited study of
      seropositive subjects with premalignant change was consistent with the fall in
      IgG2 antibody pre-dating malignant change, although pre-eradication results are
      needed to validate these data. CONCLUSIONS: These studies indicate that subjects
      with low levels of IgG2 anti-H. pylori antibody are at risk of gastric
      adenocarcinoma, and that the previously described linkage between gastric
      adenocarcinoma and low total IgG antibody does not simply reflect reduced gastric
      colonization. The diagnostic value of this assay for pre-endoscopy screening is
      attractive.

PMID- 16105119
TI  - Helicobacter pylori eradication decreases the expression of
      glycosylphosphatidylinositol-anchored complement regulators, decay-accelerating
      factor and homologous restriction factor 20, in human gastric epithelium.
AB  - BACKGROUND: It has previously been reported that there is a strong correlation
      between the expression of glycosylphosphatidylinositol (GPI)-anchored complement
      membrane inhibitor in gastric epithelium and the severity of inflammation of
      gastric mucosa. To investigate the regulation of complement activity in gastric
      epithelium during Helicobacter pylori (H. pylori)-associated gastritis, the
      expression of GPI-anchored complement membrane inhibitors, decay-accelerating
      factor (DAF) and 20-kDa homologous restriction factor 20 (HRF20), and membrane
      cofactor protein (MCP), which is a transmembrane protein, were evaluated after
      removal of the H. pylori stimulus. Furthermore, the expression of the complement
      fragment, C3c, was also investigated. METHODS: Forty-six patients with epigastric
      symptoms and endoscopically confirmed peptic ulcer or gastritis who had H. pylori
      infection of the gastric mucosa were enrolled in the present study. Biopsy
      specimens were obtained from the gastric antrum and corpus 1 month before and
      after eradication. Helicobacter pylori infection was determined by the rapid
      urease test, histology, and culture before eradication, and by histology,
      culture, and urea breath test after eradication. Gastric biopsy specimens
      obtained before and after eradication were evaluated for infiltration by
      neutrophils and mononuclear cells. The expression of complement membrane
      inhibitors, DAF, HRF20, and MCP and that of the main complement fragment, C3c,
      was immunohistochemically evaluated. RESULTS: One month after the eradication of
      H. pylori, the infiltration by neutrophils and mononuclear cells in the gastric
      mucosa decreased significantly (P < 0.0001) as compared with that before
      eradication. The expression of DAF, HRF20, and C3c on gastric mucosal epithelium
      also significantly decreased in both the antrum and the corpus (P < 0.05) 1 month
      after eradication. However, no change was observed in the expression of MCP.
      CONCLUSIONS: The decrease in the expression of GPI-anchored complement regulator
      and the complement after removal of a chronic microbial stimulus suggests that
      the gastric epithelium appears to undergo an aggressive stress of complement
      during H. pylori infection. Conclusively, DAF and HRF20 may play an important
      protective role against complement-mediated damage induced by chronic microbial
      stimuli in such a pathological condition.

PMID- 16105120
TI  - Prevalence of Helicobacter pylori infection, endoscopic gastric findings and
      dyspeptic symptoms among a young Japanese population born in the 1970s.
AB  - BACKGROUND: With the prevalence of Helicobacter pylori (H. pylori) infection
      rapidly decreasing in Japan, endoscopic findings and dyspeptic symptoms need to
      be re-evaluated. METHODS: In a health check-up program, endoscopy was performed
      on 530 young Japanese subjects (371 men and 159 women) born in the 1970s.
      Helicobacter pylori infection was evaluated using serology and a rapid urease
      test. Endoscopic gastritis was classified according to the Sydney classification
      system, in addition to nodular gastritis. Dyspeptic symptoms were also recorded
      before endoscopy. RESULTS: Of the 530 subjects, 87 (16.4%) were H. pylori
      positive. Of the 443 H. pylori-negative subjects, 349 (78.8%) were considered to
      have endoscopically normal gastric mucosa. However, of the 87 H. pylori-positive
      subjects, only 19 (21.8%) tested normal (P < 0.001). The prevalence of several
      types of gastritis was significantly higher in H. pylori-positive subjects
      compared with H. pylori-negative subjects: atrophic gastritis (37.9% vs 1.1%, P <
      0.001), flat erosive gastritis (29.9% vs 7.2%, P < 0.001), rugal hyperplastic
      gastritis (12.6% vs 0.0%, P < 0.001), and nodular gastritis (13.8% vs 0.0%, P <
      0.001). Other types of gastritis were not related to H. pylori status. The
      prevalence of subjects with dyspeptic symptoms was significantly higher in H.
      pylori-positive subjects compared with H. pylori-negative ones (28.7% vs 6.5%, P
      < 0.001). CONCLUSION: It is suggested that in consideration of its recent low
      prevalence and the slow increase in its infection, the prevalence of H. pylori
      related gastritis will gradually decrease in Japan. Further studies will be
      required to ascertain if there is a need for H. pylori eradication in this young
      population.

PMID- 16105121
TI  - Comparison between coefficient of R-R interval variation and gastric emptying in
      type 2 diabetes mellitus patients.
AB  - BACKGROUND: Autonomic neuropathy is a common complication of diabetes mellitus
      (DM). METHOD: To clarify the relationship between cardiovascular autonomic
      function and gastric emptying rate, we investigated the gastric emptying and
      coefficient of R-R interval variation (CV(RR)) of 84 type 2 diabetic patients: 28
      cases without peripheral neuropathy and 56 cases with peripheral neuropathy. All
      patients were subjected to a gastric emptying test according to the marker method
      (administration of a capsule containing 20 pieces of radiopaque marker during
      breakfast, followed by abdominal X-ray imaging 3 and 5 h later). Patients had
      their CV(RR) assessed at rest and during deep breathing. RESULTS: Gastric
      emptying scores were significantly correlated with CV(RR) during deep breathing
      and with the duration of DM, but neither age nor CV(RR) at rest in all patients.
      Gastric emptying scores and CV(RR) at rest and during deep breathing in patients
      with peripheral neuropathy were significantly deteriorated than those in patients
      without peripheral neuropathy. A significant correlation between gastric emptying
      and CV(RR) during deep breathing could be observed in the patients with
      peripheral neuropathy, but not in those without it. CONCLUSIONS: These findings
      showed that CV(RR) during deep breathing might be a good indicator of diabetic
      gastropathy and that peripheral neuropathy was closely related with cardiac and
      gastric autonomic neuropathy in the type 2 diabetic patients.

PMID- 16105122
TI  - Management of symptoms in step-down therapy of gastroesophageal reflux disease.
AB  - OBJECTIVE: Majority of studies on gastroesophageal reflux disease (GERD) that
      include patients with or without erosive disease have documented the efficacy of
      proton pump inhibitors (PPIs) as well as their superiority to H(2)-receptor
      antagonist (H(2)-RA). The purpose of this study was to clarify the difference in
      quality of GERD treatment with PPIs and H(2)-RA in step-down protocol using
      lansoprazole. METHODS: Forty-three patients with reflux esophagitis were randomly
      divided into three groups and assessed by severity score; group 1 received 30 mg
      lansoprazole initially and maintenance therapy with a standard dose H(2)-RA;
      group 2 received 30 mg of lansoprazole initially and maintenance therapy of 15 mg
      lansoprazole; and group 3 received 15 mg of lansoprazole once daily for 16 weeks.
      If the patients experienced symptomatic recurrence while on H(2)-RA, they were
      switched to PPI maintenance. RESULTS: Heartburn, regurgitation and dysphagia were
      hardly found in any group at 8 weeks after 15 mg or 30 mg lansoprazole treatment.
      After 8 weeks, however, heartburn and regurgitation recurred at 50% and 78.6%,
      respectively, in the stepped down to famotidine group, and quality of life (QOL)
      was significantly impaired. Endoscopic ultrasonography (EUS) analysis showed
      reduction of the submucosal layer without any change in the mucosal surface in
      the stepped down to famotidine group. CONCLUSIONS: Step-down lansoprazole therapy
      is considered very effective in terms of rapid effect, long-term effect and high
      quality GERD treatment.

PMID- 16105123
TI  - Tumor cell dissociation score highly correlates with lymph node metastasis in
      superficial esophageal carcinoma.
AB  - BACKGROUND: It is still not clear which parameters are important for predicting
      the metastatic potential of superficial esophageal squamous cell carcinoma
      (SESCC). The purpose of the present paper was thus to investigate tumor cell
      dissociation (TCD) in SESCC as a predictive factor of lymph node metastasis.
      METHODS: Thirty-three SESCC were classified into four groups based on the depth
      of tumor invasion. Carcinomas not invading as far as the muscularis mucosa were
      classified as group A; carcinomas invading to the muscularis mucosa or less than
      one-third of the upper submucosa were classified as group B; those invading to
      the middle layer of the submucosa were classified as group C; and those invading
      one-third of the lower submucosa were classified as group D. The TCD score was
      calculated by dividing the length of the TCD region by the maximal longitudinal
      length of the area of invasion into or beyond the lamina propria, and multiplying
      by 100. E-cadherin expression of the carcinomas was investigated in the TCD area
      and the successive area of mucosal invasive carcinoma (SAM). RESULTS: The
      incidence of lymph node metastasis was 0% in group A, 10% in group B, 36.4% in
      group C and 57.1% in group D. The mean TCD scores (+/-SEM) of SESCC with lymph
      node metastasis were higher than that without (85.3 +/- 5.7, 16.3 +/- 3.9,
      respectively; P < 0.001). In group C, the TCD score of cases with lymph node
      metastases was higher than in those without lymph node metastasis (P < 0.001). E
      cadherin expression was significantly reduced in the area of TCD compared with
      the SAM located over the TCD area (P < 0.001). CONCLUSIONS: The TCD score is an
      important predictive marker for lymph node metastasis in SESCC. Clinical
      evaluation of TCD scores in endoscopic mucosal resection (EMR) specimens would
      enable accurate prediction of lymph node metastasis and extend the indication of
      EMR treatment for SESCC.

PMID- 16105124
TI  - Long-term follow up results of intraductal papillary mucinous tumors of pancreas.
AB  - BACKGROUND AND AIM: Intraductal papillary mucinous tumor (IPMT) of the pancreas
      can be divided into three clinically distinct subtypes: main duct type, branch
      duct type and mixed type. Although it has been reported that the branch duct type
      IPMT is less invasive than the main duct type IPMT, we experienced a number of
      branch duct type IPMT having a poor prognosis. In the present study we surveyed
      the survival and recurrence rates according to the subtypes. METHODS: Sixty-seven
      IPMT cases were studied to investigate clinical behavior according to the duct
      types. Diagnostic findings and late results of treatment were reviewed in 27
      cases of the main duct type IPMT and in 35 cases of the branch duct type IPMT.
      RESULTS: There was no statistically significant difference in the survival
      analysis between the main duct type IPMT and the branch duct type IPMT (P =
      0.93). Seven patients (25.9%) died among the main duct type IPMT while six
      patients (17.1%) died among the branch duct type IPMT (P = 0.36). Tumor
      recurrence was noticed in four patients (18.1%) among 22 operated main duct type
      IPMT and in two patients (6.9%) among 29 operated branch duct type IPMT (P =
      0.35). CONCLUSION: The long-term follow up result of the branch duct type IPMT is
      similar to that of the main duct type IPMT. Therefore, it is not safe just to
      monitor the branch duct type IPMT without operation. Surgery, whenever possible,
      is clearly the gold standard for treatment of IPMT, regardless of duct type.

PMID- 16105125
TI  - Oral refeeding in patients with mild acute pancreatitis: prevalence and risk
      factors of relapsing abdominal pain.
AB  - BACKGROUND AND AIM: In acute pancreatitis (AP), oral refeeding may stimulate
      pancreatic secretion, increasing the inflammation of the glandular tissue causing
      relapse of abdominal pain or even exacerbation of the disease. This study aimed
      to assess the prevalence and risk factors of abdominal pain relapse over oral
      refeeding in patients convalescing with AP as well as the impact of pain
      recurrence on the hospital stay. METHODS: Inclusion criteria were AP confirmed by
      biochemical and/or radiological data in the absence of severe disease or
      extensive necrosis. The same diet was offered to all patients during oral
      refeeding. Demographic, clinical, biochemical and radiological data were
      prospectively recorded and analyzed. RESULTS: A total of 130 patients were
      included. During the oral refeeding period, 32 (24.6%) patients had pain relapse,
      which was more common on days 1 (68.8%) and 2 (28.1%). Pain relapse was related
      to higher serum levels of lipase on the day before refeeding, higher serum levels
      of C-reactive protein on the fourth day, and presence of peripancreatic fluid
      collections (P < 0.01). Pain relapse significantly increased total hospital stay
      (P < 0.01). CONCLUSIONS: In patients with mild AP, pain relapse during oral
      refeeding was relatively high (24.6%), particularly on the first or second day.
      Their risk appeared be associated with more intense or persistent pancreatic
      inflammation on the day before refeeding, and presence of peripancreatic fluid
      collections. Pain relapse increased hospital stay, and likely overall costs on
      disease treatment.

PMID- 16105126
TI  - No correlation between clinical symptoms and Blastocystis hominis in
      immunocompetent individuals.
AB  - Abstract Background and Aim: Previous reports regarding the clinical significance
      and pathogenicity of Blastocystis hominis have been contradictory. The aim of
      this study was to examine the association between Blastocystis and
      gastrointestinal symptoms in immunocompetent individuals. METHODS: We monitored
      over 2800 healthy people for a period of 15 months, and took stool specimens
      during both asymptomatic periods and during periods of gastrointestinal symptoms.
      RESULTS: After exclusion of individuals who had simultaneous identification of
      other fecal pathogens, we compared the proportions of asymptomatic versus
      symptomatic individuals positive for Blastocystis and found no significant
      difference (P = 0.5). Symptom status did not correlate with parasite abundance.
      We found that some individuals were likely to have Blastocystis detected during
      both asymptomatic and symptomatic periods, possibly suggesting carriage of the
      organism. CONCLUSION: In conclusion, we found no correlation between clinical
      symptoms and the presence or absence of Blastocystis among this healthy cohort.

PMID- 16105127
TI  - Hepatic steatosis and the risk of hepatocellular carcinoma in chronic hepatitis
      C.
AB  - BACKGROUND AND AIM: Obesity associated hepatic steatosis has been suggested to
      have a premalignant potential. We determined whether hepatic steatosis
      predisposes to liver cancer in persons with chronic hepatitis C virus (HCV)
      infection. METHODS: We compared the histological severity of steatosis in the
      index liver biopsies of 25 patients with chronic hepatitis C who subsequently
      developed hepatocellular carcinoma (HCC) with matched controls who did not. Cases
      were aged (mean) 54.7 years, 84% males, 76% genotype 1, and 64% fibrosis stage 4;
      and controls were matched for these characteristics. Those with a sustained
      virologic response to antiviral therapy were excluded. RESULTS: Duration of HCV
      infection, concomitant alcohol intake, body mass index and indices of past
      hepatitis B virus (HBV) infection were comparable between the groups. Controls
      were followed for a longer period after the index liver biopsy than were cases
      (113 months vs 55 months, P < 0.001). As determined by percentage area of biopsy
      core occupied by steatosis on computer assisted morphometric evaluation, and
      graded by semiquantitative histological assessment, steatosis was comparable
      among cases and controls. The odds of developing HCC among those with steatosis
      grades 1 and 2 did not differ significantly from those without steatosis. There
      was no association between increasing morphometric percentage area occupied by
      steatosis and the subsequent development of HCC. Neither steatosis grade or
      percent area of steatosis on biopsy were selected in multivariate regression
      analysis as independent predictors for the development of HCC. CONCLUSIONS:
      Hepatic steatosis does not augment the risk of hepatocarcinogenesis in patients
      with chronic HCV infection.

PMID- 16105128
TI  - Mutations in the NS5B region of the hepatitis C virus genome correlate with
      clinical outcomes of interferon-alpha plus ribavirin combination therapy.
AB  - BACKGROUND AND AIM: Combination treatments of interferon-alpha (IFN) and
      ribavirin (RBV) are more effective than those of IFN alone in hepatitis C virus
      (HCV) infection. However, mechanisms of the action of the combination regimen are
      not well understood. To elucidate the viral genetic basis of IFN plus RBV
      combination therapy, genetic variabilities of HCV-1b were analyzed. METHODS: We
      performed pair-wise comparisons of full-length HCV genomic sequences in three
      patients' sera before and after initiation of IFN plus RBV treatment.
      Subsequently, we analyzed amino acid sequences of the NS5B region, which codes
      for the viral RNA-dependent RNA polymerase, and compared these with the outcomes
      of the therapy in 81 patients. RESULTS: Analysis of the entire HCV sequence in
      patients who received IFN plus RBV therapy did not show consistent amino acid
      changes between before and after the initiation of the therapy. NS5B sequence
      analyses revealed that mutations at positions 300-358 of NS5B, including
      polymerase motif B to E, occurred more frequently in a group of patients
      exhibiting a sustained viral response (SVR) or an end-of-treatment response (ETR)
      compared with a group of patients exhibiting a non-response (NR). Closer
      examination revealed that mutations at aa 309, 333, 338 and 355 of NS5B occurred
      significantly more frequently in the SVR plus ETR group than in the NR group (P =
      0.0004). Multivariate analysis showed that the number of mutations at these four
      sites was an independent predictor of SVR plus ETR versus NR. CONCLUSIONS:
      Particular amino acid changes in the NS5B region of HCV may correlate with
      outcomes of IFN plus RBV combination therapy.

PMID- 16105129
TI  - Association between adenomas of rectosigmoid colon and metabolic syndrome
      features in a Chinese population.
AB  - BACKGROUND AND AIMS: Metabolic syndrome (MS) consists of a cluster of diseases,
      including obesity, dyslipidemia, hyperglycemia and high blood pressure. The
      purpose of the present study was to assess the association of MS with adenomas of
      the rectosigmoid colon, a well-established precancerous lesion. METHODS: A total
      of 4938 Taiwanese patients (2891 men and 2047 women with a mean age of 50.1
      years), who had a physical examination at our hospital between January 2001 and
      October 2002, were enrolled in this study. All patients underwent a
      sigmoidoscopic examination to 60 cm from the anus. A modified National
      Cholesterol Education Program (NCEP) definition of MS was used in this study, in
      which body mass index (BMI) was substituted for the waist circumference
      measurement. RESULTS: Overall, 14% of patients had an elevated fasting glucose,
      27% had high blood pressure, 14% had an increased triglyceride (TG) level, 8% had
      low high density lipoprotein (HDL) cholesterol, and 18% were obese. Rectosigmoid
      polyps were present in 17% of patients, among whom 568 received polypectomy.
      Pathological findings were hyperplastic in 138 subjects, adenomas in 341,
      carcinomas in 10, and other benign lesions in 79. In patients without polyps, the
      adjusted mean TG level and calculated BMI level were lower than those in patients
      with adenomas. No such difference existed, however, between patients without
      polyps and those with hyperplastic polyps. The odds ratio of adenomas in situ as
      compared to either a polyp-free state or the presence of hyperplastic polyps
      increased significantly with the number of MS diagnostic criteria the patient
      exhibited. CONCLUSION: Our study shows that MS is associated with rectosigmoid
      adenomas in a Chinese population. In patients with rectosigmoid polyps, the
      coexistence of MS may portend an increased risk of adenomas.

PMID- 16105130
TI  - Hepatitis C virus infection facilitates gallstone formation.
AB  - BACKGROUND: Bile duct damage and hepatic steatosis are two characteristic
      histological findings in hepatitis C virus infection; and high prevalence of
      hepatitis C antibody is noted in patients with cholangiocarcinoma. The purpose of
      the present study was to examine the relationship between biliary diseases and
      hepatitis C virus infection. METHODS: Persons who received a general checkup in
      Chang Gung Memorial Hospital between 2000 and 2002 were included. All of them had
      hemogram, serum biochemistry, hepatitis B surface antigen, hepatitis C antibody
      and ultrasonography studies. The prevalence of gallbladder stone, bile duct stone
      and gallbladder polyp/cholesterolosis were compared in different viral infection
      groups. RESULTS: Of the 28 486 persons, 22 967 were negative for both hepatitis B
      surface antigen and hepatitis C antibody (group NBNC), 4152 were hepatitis B
      surface antigen carriers (broup B), 1195 were positive for hepatitis C antibody
      (group C), and 172 were positive for both markers. The 379 persons (1.3%) having
      had cholecystectomy were considered to have gallbladder stone at the time when
      cholecystectomy was done. Gallbladder stone was found in 6.0% persons of group
      NBNC, 5.4% in group B and 11.7% in group C. The prevalence of gallbladder stone
      in group C was found especially high for age groups 31-40 years and 61-70 years.
      The prevalence of bile duct stone was higher in group C (0.4%) than in group NBNC
      or B (both 0.1%). Stepwise logistic regression analysis showed that age, liver
      cirrhosis, body mass index, hepatitis C virus infection and gender were
      independent factors associated with gallbladder stone. CONCLUSIONS: Hepatitis C
      virus infection facilitates gallstone formation.

PMID- 16105131
TI  - Hepatocellular carcinoma and octreotide: treatment results in prospectively
      assigned patients with advanced tumor and cirrhosis stage.
AB  - BACKGROUND AND AIM: Treatment of inoperable hepatocellular carcinoma (HCC)
      remains a major clinical problem. The only efficient treatment options are
      percutaneous ethanol injection (PEI), radiofrequency ablation (RF) and
      transarterial chemoembolization (TACE), but these therapies are only applicable
      to patients with limited tumor spread and sufficient liver function. For patients
      with advanced tumor and poor liver function a systemic therapy is required.
      Octreotide, a somatostatin analog with antimitotic activity, is a controversial
      treatment option. METHODS: In the current study we prospectively assigned a group
      of 41 HCC patients with advanced HCC and cirrhosis stage to treatment with
      octreotide. The clinical and laboratory parameters were monitored and survival
      was analyzed using a Cox regression model. RESULTS: The medium survival in the
      group of all patients was 571 days. Using the Cox regression there was a
      significant difference in survival for alpha-fetoprotein (P = 0.026) and Quick's
      test (P = 0.009) in consideration of the tumor dimension compared to the other
      characteristics. The tumor remained stable in 26 patients over a mean follow-up
      of 21 months and progressed in 14 patients. One patient showed a partial
      response. There was no incidence of severe side-effects (WHO grade 3-4). During
      the follow-up time, 14 patients died because of their underlying disease.
      CONCLUSIONS: Treatment with octreotide appears safe and patients show similar
      survival compared to a group of patients with advanced HCC treated with TACE.
      Further studies are necessary to investigate somatostatin receptor subtypes or
      receptor mutations of patients with advanced HCC in relation to their response.

PMID- 16105132
TI  - Alteration of the expression of adenosine triphosphate-binding cassette
      transporters associated with bile acid and cholesterol transport in the rat liver
      and intestine during cholestasis.
AB  - BACKGROUND AND AIM: Multidrug resistance protein 2 (Mrp2), Mrp3, adenosine
      triphosphate-binding cassette transporter g5 (Abcg5) and adenosine triphosphate
      binding cassette transporter g8 (Abcg8) have been identified as bile acid or
      cholesterol transporter in the enterocytes as well as hepatocytes. The purpose of
      the present study was to evaluate intestinal and hepatic adenosine triphosphate
      binding cassette transporter expressions during cholestasis. METHODS: Experiment
      1: Rats were subjected to bile duct ligation or sham operation. Blood, liver and
      small intestines were obtained 24 and 72 h after operation. Experiment 2: Rats
      were divided into four groups as follows: (i) control group; (ii) diosgenin group
      (fed with diosgenin in diet [1%(wt/wt)] for 7 days); (iii) ethinyl estradiol
      group (received ethinyl estradiol [5 mg/kg daily] for 5 days); and (iv) diosgenin
      ethinyl estradiol group (received ethinyl estradiol and diosgenin). After
      treatment, blood, bile, liver and intestines were obtained. The mRNA related to
      lipid and bile acid metabolism was analyzed by reverse transcription polymerase
      chain reaction. RESULTS: Intestinal Mrp2 and Abcg5/Abcg8 mRNA expression
      remarkably decreased 24 h after bile duct ligation (43% and 61%/54% of sham
      operation) and recovered 72 h after bile duct ligation (103% and 95%/83% of sham
      operation). Intestinal Mrp3 mRNA expression did not change after bile duct
      ligation. Intestinal Mrp2 mRNA expression was remarkably increased in diosgenin
      and diosgenin-ethinyl estradiol groups in comparison with the control group.
      There were no significant differences in intestinal Mrp3 mRNA expression among
      the four groups. Hepatic Mrp3 mRNA expression was remarkably increased in the D,
      EE and DE groups in comparison with the control group (531%, 321% and 1160% of
      control, respectively, P < 0.01). Hepatic Abcg5 and Abcg8 mRNA expression
      decreased in ethinyl estradiol and diosgenin-ethinyl estradiol groups compared
      with the control group and there were no differences in intestinal Abcg5 and
      Abcg8 mRNA expressions among the four groups. CONCLUSION: Bile duct ligation
      affects not only hepatic but also the intestinal Mrp2 and Abcg5 and Abcg8
      expressions. Intestinal Mrp2 mRNA level was regulated by factor in the lumen
      (e.g. diosgenin feeding). Cholestasis by ethinyl estradiol treatment was enhanced
      by diosgenin and the increase in hepatic Mrp3 mRNA level might affect the
      enhancement.

PMID- 16105133
TI  - Effects of HFE gene mutations and alcohol on iron status, liver biochemistry and
      morbidity.
AB  - BACKGROUND AND AIMS: The aims of the present study were to determine: (i) whether
      alcohol consumption is greater in individuals with HFE mutations; and (ii)
      whether common HFE mutations modify the effects of alcohol on serum iron and
      liver biochemistry or morbidity. METHODS: The residents of the town of Busselton
      in Western Australia were subject to cross-sectional health surveys between 1966
      and 1983. In 1994/1995 all surviving participants of the earlier surveys were
      invited to take part in a follow-up survey. Logistic, linear and Poisson log
      linear regression analyses were performed in 1490 men and 1452 women from the
      1994/1995 survey to assess the relationships between HFE mutations, alcohol, iron
      levels, liver biochemistry and morbidity. RESULTS: Heavy or moderate alcohol
      consumption was present in 7% or 36% of men and 0.5% or 12% of women,
      respectively. Alcohol consumption strongly influenced levels of serum ferritin
      and gamma glutamyl transpeptidase (GGT) and mean cell volume (MCV) in men and
      women but only alanine aminotransferase (ALT) levels in women. These effects were
      independent of HFE gene mutations. Hospital admission rates for respiratory
      disorders were higher in men with the C282Y mutation. CONCLUSIONS: Alcohol
      consumption strongly influences serum ferritin and GGT levels and MCV in men and
      women but only ALT levels in women, and these effects are independent of HFE
      mutations. HFE gene mutations do not predispose to moderate or heavy alcohol
      consumption. The C282Y mutation is associated with increased respiratory
      admission rates in men.

PMID- 16105134
TI  - Results of alcohol and albendazole injections in hepatic hydatidosis:
      experimental study.
AB  - BACKGROUND: Percutaneous drainage with alcohol injection for hydatid cysts has
      been commonly used in the last two decades. Albendazole is the drug of choice in
      the medical treatment of hydatidosis, and has also been used as an intraoperative
      scolicidal solution. The side-effects of its local application are not well known
      and have not been investigated. The purpose of the present study was to
      investigate the effects of the intracystic injections of alcohol and albendazole
      solutions on the hydatid cysts and hepatobiliary system of rabbits. METHODS:
      There were three groups of eight rabbits: a control group, an alcohol group and
      an albendazole group. In all groups hepatic hydatidosis was obtained. The control
      group received no therapeutic procedure. Cyst liquid was aspirated, and alcohol
      or albendazole solutions were injected in the other two study groups. alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl
      transferase (GGT) levels, echinococcus indirect hemagglutination (IHA) tests, and
      the size and volume of the residual cysts were investigated. Liver was
      histopathologically evaluated. RESULTS: The ALT, AST, GGT, and alkaline
      phosphatase (ALP) levels were significantly higher in the alcohol group, whereas
      echinococcus IHA level was highest in the control group than in the study groups.
      Albendazole had similar effects but of a lesser degree (P < 0.01). After therapy,
      the cyst volume was greater in the control than in the albendazole group (P <
      0.01). In histopathological evaluation hepatocellular necrosis, portal
      inflammation and fibrosis were most severe in the alcohol group (P < 0.01).
      CONCLUSIONS: Alcohol and albendazole solutions are effective as scolicidal
      solutions. Higher scolicidal effect and lesser side-effects on hepatobiliary
      system are the advantages of albendazole solution.

PMID- 16105135
TI  - Elevated plasma homocysteine concentrations as a predictor of steatohepatitis in
      patients with non-alcoholic fatty liver disease.
AB  - BACKGROUND: Although steatosis is common in patients with severe
      hyperhomocysteinemia due to deficiency of cystathionine beta-synthase, there are
      no satisfactory data on homocysteine concentrations in patients with non
      alcoholic fatty liver disease. The main aim of the present study was to evaluate
      the clinical significance of plasma homocysteine concentrations in patients with
      non-alcoholic fatty liver disease. METHODS: Seventy-one non-alcoholic fatty liver
      disease patients, 36 patients with chronic viral hepatitis and 30 healthy persons
      were enrolled in the study. Homocysteine levels were measured by high-performance
      liquid chromatography. Insulin, folate, vitamin B(12) and lipoprotein levels were
      also determined in all groups. RESULTS: Homocysteine in the non-alcoholic fatty
      liver disease group was found to be significantly higher than other groups.
      Homocysteine was found to be significantly higher in the non-alcoholic
      steatohepatitis group when compared with simple steatosis group. A positive
      correlation was found between homocysteine and triglyceride, very-low-density
      lipoprotein (VLDL) cholesterol, insulin, and index of insulin resistance in the
      non-alcoholic fatty liver disease group, and a negative correlation was found
      between homocysteine and folate, or vitamin B(12) in all groups. The homocysteine
      threshold for the prediction of steatohepatitis was 11.935 ng/mL. Furthermore;
      plasma homocysteine was a statistically significant predictor for severity of
      necroinflammatory activity in non-alcoholic steatohepatitis. CONCLUSIONS: The
      plasma homocysteine concentrations were significantly higher in patients with non
      alcoholic fatty liver disease, while the concentrations were not affected by
      chronic viral hepatitis. Plasma homocysteine is a parameter for discriminating
      steatohepatitis from simple steatosis. Determining the plasma homocysteine
      concentrations may facilitate selection of steatosis patients in whom a liver
      biopsy should be performed.

PMID- 16105136
TI  - Gastrointestinal: acid injury to the stomach.

PMID- 16105137
TI  - Gastrointestinal: acute mesenteric ischemia.

PMID- 16105138
TI  - Gastrointestinal: ischemic colitis associated with colon cancer.

PMID- 16105139
TI  - Hepatobiliary and pancreatic: mucinous carcinoma of the pancreas.

PMID- 16105140
TI  - Hepatobiliary and pancreatic: simple pancreatic cysts.

PMID- 16105141
TI  - Cardiac glands hyperplastic polyp of the stomach.
AB  - Reported herein is a very rare polyp in the gastric cardia of a 49-year-old man.
      He was referred because of a polyp detected by upper gastrointestinal examination
      in an affiliated hospital. Endoscopic examination revealed a polyp-like
      submucosal tumor. Endoscopic ultrasonography revealed minute cystic dilatations
      and thickening of the submucosal layer. Accordingly, a preliminary diagnosis of
      cardiac gland hyperplasia was made. The lesion was removed successfully by snare
      polypectomy. Observed macroscopically, the polyp was 30 mm in diameter and
      covered with normal gastric mucosa. Examined histologically, the polyp comprised
      a hyperplastic submucosal cardiac gland.

PMID- 16105142
TI  - Successful treatment with adalimumab in infliximab-resistant Crohn's disease.

PMID- 16105143
TI  - Iodized oil embolization to brain following transcatheter arterial embolization
      of liver.

PMID- 16105144
TI  - Embryo extracts opotherapy reduces alpha-fetoprotein levels in hepatocellular
      carcinoma patients.

PMID- 16105145
TI  - Cytophagic hemorrhagic panniculitis and severe steatohepatitis: challenging
      combination.

PMID- 16105146
TI  - Long-term complete remission of metastatic gastric cancer after weekly docetaxel,
      24 h infusion of high-dose 5-FU/leucovorin and cisplatin.

PMID- 16105147
TI  - Determinants of non-response in Helicobacter pylori eradication trials.

PMID- 16105148
TI  - Acute portal vein occlusion in a patient with Crohn's disease.

PMID- 16105149
TI  - Dilemma of medical education re-visited.

PMID- 16105150
TI  - Could lymphoma be the underlying disease in this patient with pyrexia of unknown
      origin?

PMID- 16105151
TI  - Effects of opioids and sedatives on survival in an Australian inpatient
      palliative care population.
AB  - AIMS: To assess whether opioid and sedative medication use affects survival (from
      hospice admission to death) of patients in an Australian inpatient palliative
      care unit. BACKGROUND: Retrospective audit. Newcastle Mercy Hospice--a tertiary
      referral palliative care unit. All patients who died in the hospice between 1
      February and 31 December 2000. METHODS: Length of survival from hospice admission
      to death, and the median and mean doses of opioids and sedatives used in the last
      24 h of life. Comparison of these with published studies outside of Australia.
      RESULTS: In this study, the use of opioids, benzodiazepines and haloperidol did
      not have an association with shortened survival and the only statistical
      significant finding was an increased survival in patients who were on 300 mg/day
      or more of oral morphine equivalent (OME). The proportion of patients requiring
      greater than or equal to 300 mg OME/day (at 28%) was higher than published
      studies, but the mean dose of 371 mg OME/day was within the range of other
      studies. The proportion of patients receiving sedatives (94%) was higher than
      other studies, but the median dose of parenteral midazolam equivalent of 12.5 mg
      per 24 h was lower than other studies from outside Australia. CONCLUSIONS: There
      was no association between the doses of opioids and sedatives on the last day of
      life and survival (from hospice admission to death) in this population of
      palliative care patients.

PMID- 16105152
TI  - Randomized double-blind trial of sotalol versus lignocaine in out-of-hospital
      refractory cardiac arrest due to ventricular tachyarrhythmia.
AB  - AIM: We aimed to compare the efficacy of sotalol versus lignocaine for the
      treatment of patients with out-of-hospital ventricular fibrillation refractory to
      > or = 4 defibrillatory shocks. BACKGROUND: The outcome of patients in
      ventricular fibrillation refractory to > or = 4 defibrillatory shocks is poor. In
      a previous randomized trial, sotalol was superior to lignocaine for acute
      termination of ventricular tachycardia not causing loss of consciousness.
      METHODS: Patients of the Ambulance Service of New South Wales treated by
      paramedics with continued ventricular fibrillation despite standard resuscitation
      and > or = 4 defibrillatory monophasic shocks were eligible. Drug doses were
      sotalol 100 mg or lignocaine 100 mg, given as i.v. boluses. A further 2 min of
      cardiopulmonary resuscitation was given and then defibrillation was repeated
      twice. If this failed, half the initial dose of the trial drug was repeated and a
      further > or = 2 shocks were given. RESULTS: Sixty patients were randomized to
      sotalol and 69 randomized to lignocaine. There was no significant difference
      between the two groups in the clinical characteristics of the patients or in the
      number of shocks received. Outcomes in the sotalol and lignocaine groups were
      survival to hospital admission in 7 (12%) and 16 (23%), respectively (P = 0.09),
      and survival to hospital discharge in 2 (3%) and 5 (7%), respectively (P = 0.33).
      CONCLUSIONS: Sotalol is not superior to lignocaine for treatment of ventricular
      fibrillation refractory to multiple shocks. The overall outcome of this group of
      patients is poor regardless of the pharmacological intervention (lignocaine or
      sotalol).

PMID- 16105153
TI  - Stool antigen testing for the diagnosis and confirmation of eradication of
      Helicobacter pylori infection: a prospective blinded trial.
AB  - BACKGROUND AND AIMS: Helicobacter pylori is an established pathogen for a wide
      spectrum of gastroduodenal diseases. We investigated the usefulness of H. pylori
      stool antigen test (HpSA) before and after eradication therapy on patients
      referred for gastroscopy. METHODS: Over a 12-month period, 127 adult patients
      (47% males) underwent HpSA and gastroscopy with dual biopsies from the antrum and
      proximal body of the stomach for urease and histology. The positive patients
      (histology, urease or combined positive) received triple therapy consisting of
      clarithromycin 500 mg, amoxycillin 1 g and omeprazole 20 mg, each given twice
      daily for 7 days. Six weeks post-therapy, eradication was verified with the 13C
      urea breath test (UBT) and the HpSA results compared on a second stool sample.
      RESULTS: Pre-therapy, 23/113 patients were positive by urease test, 22/112 by
      histology and 22/112 were combined positive. For the HpSA, compared to combined
      urease and histology as the reference standards, the sensitivity and specificity
      were 79 and 92% while the positive and negative predictive values (PPV and NPV)
      were 68 and 96%, respectively. Post-therapy, UBT was adopted as the reference
      standard and 18 paired samples were available for analysis: three were positive
      and 15 were negative. Sensitivity and specificity were 67 and 100% while the PPV
      and NPV were 100 and 94%, respectively. CONCLUSIONS: In this prospective study,
      HpSA was found to be a reasonably useful diagnostic test for H. pylori infection.
      Post-eradication, it was highly specific and similar to UBT in terms of PPV and
      NPV. The test is non-invasive and cheaper than the urease test or the UBT, making
      it a candidate in the investigation of dyspepsia.

PMID- 16105154
TI  - Epiglottitis in Sydney before and after the introduction of vaccination against
      Haemophilus influenzae type b disease.
AB  - BACKGROUND: Acute epiglottitis due to infection with Haemophilus influenzae type
      b (Hib) is much less common in children following the introduction of Hib
      vaccination; however, adult epiglottitis cases have not decreased. In addition,
      epiglottitis hospitalizations are consistently more numerous than notifications
      and the reason for this is not clear. AIMS: To more accurately describe the
      clinical, aetiological and epidemiological features of epiglottitis and to
      ascertain the accuracy of hospitalization data in an era of widespread Hib
      vaccination. METHODS: Medical records in 11 public hospitals in three area health
      services in New South Wales with a principal or stay diagnosis (International
      Classification of Diseases (ICD)-9-CM or ICD-10-AM code) of acute epiglottitis
      between July 1990 and June 1992 (prior to Hib vaccination = pre-vaccine era) and
      July 1998 and June 2000 (widespread Hib vaccination = vaccine era) were reviewed.
      Case definitions of epiglottitis were applied. RESULTS: One hundred and forty-two
      records were identified (114 pre-vaccine era and 28 vaccine era). Incorrect
      coding was more common in vaccine era records (32 vs 7%). Of correctly coded
      records, adults over 20 years old comprised the majority in the vaccine era (84
      vs 17%). Hib bacteraemia was identified in 62% of cases in the pre-vaccine era
      compared to no cases in the vaccine era, despite equivalent blood cultures being
      taken between the two eras (84 vs 74%). Streptococcus pneumoniae was the only
      other organism isolated. Three deaths were recorded (1 child, 2 adults), all in
      the pre-vaccine era. CONCLUSIONS: Acute epiglottitis hospitalizations in the
      current Hib vaccine era are predominantly in adults, and rarely are Hib or other
      causative organisms identified, although microbiological data are often
      incomplete. The discrepancy between hospitalization and notification data appears
      to be due to misclassification of hospitalization records.

PMID- 16105155
TI  - Glargine is superior to neutral protamine Hagedorn for improving glycated
      haemoglobin and fasting blood glucose levels during intensive insulin therapy.
AB  - AIM: To compare glycaemic control and symptomatic hypoglycaemia rates with
      glargine versus neutral protamine Hagedorn (NPH) in poorly controlled type 1
      diabetes patients. METHODS: Patients (n = 125) received preprandial insulin
      lispro and either glargine (n = 62) or NPH (n = 63) at bedtime for 30 weeks in a
      multicentre, randomized, single-blind (a blinded investigator made titration
      decisions) study. Basal insulin dosage was titrated to achieve fasting blood
      glucose (FBG) values < 5.5 mmol/L. RESULTS: Baseline characteristics were similar
      for the two groups (mean diabetes duration 17.5 +/- 10.1 years) except mean
      glycated haemoglobin (HbA(1c)), which was lower in the glargine versus NPH group
      (9.2 +/- 1.1% vs 9.7 +/- 1.3%; P < 0.02). At end-point, mean HbA(1c) was 8.3
      versus 9.1% for the glargine versus NPH groups. Adjusted least-squares mean (LSM)
      change from baseline was -1.04 versus -0.51%, a significant treatment benefit of
      0.53% for HbA(1c) in favour of glargine (P < 0.01). Mean baseline FBG were
      similar for the glargine and NPH groups (11.2 vs 11.4 mmol/L). The means for end
      point FBG were 7.9 versus 9.0 mmol/L. Adjusted LSM change from baseline was -3.46
      versus -2.34 mmol/L, with a significant difference of 1.12 mmol/L in favour of
      glargine (P < 0.05). There were similar total numbers of daytime mild, moderate
      or severe hypoglycaemia episodes in the two treatment arms. However,
      significantly fewer moderate or severe nocturnal hypoglycaemic episodes were
      observed in the glargine group (P = 0.04 and P = 0.02). CONCLUSION: Glargine is
      superior to NPH for improving HbA(1c) and FBG levels during intensive insulin
      therapy in patients with type 1 diabetes, and is associated with less severe
      nocturnal hypoglycaemia.

PMID- 16105156
TI  - Difficult asthma in adults: recognition and approaches to management.
AB  - Difficult asthma must be distinguished from severe asthma. It is then important
      in patients with suspected difficult asthma to ensure that the diagnosis is
      correct, and that if the patient has asthma that the attributed symptoms are
      indeed all genuinely due to the asthma and not to coexisting physical or
      psychogenic respiratory conditions. It is also important to be alert when there
      is discordance between symptoms and objective lung function in order to recognize
      both poor perceivers and over-reactors. Difficult asthma can occur in patients
      with objectively mild, moderate or severe disease, but the consequences are most
      dramatic in patients with severe asthma. Asthma may be difficult for the patient,
      for the clinician or both because of disease factors, doctor or nurse therapist
      factors, and/or patient factors. Investigation requires access to the full range
      of respiratory, imaging and allergy tests. It also requires a multidisciplinary
      approach involving ear, nose and throat specialists and speech therapists, and
      access to psychiatric and psychological assessment and therapies. Poor compliance
      is associated with significantly poorer asthma and asthma-related health
      outcomes. Poor compliance can be recognized in two-thirds of such patients by
      their not attending scheduled appointments. Poor compliance is significantly
      associated with anxiety, social deprivation and adverse family circumstances, and
      these characteristics and adversities probably contribute to the poorly compliant
      behaviour. In difficult asthma it is important to identify and manage the
      condition causing the symptoms rather than prescribing more and more asthma
      therapy. Recognizing psychosocial adversity is essential. A structured approach
      is essential. There remains a small number of patients with genuine steroid
      resistant asthma, some with predominately neutrophilic rather than eosinophilic
      airway inflammation, and others for whom the secondary gain of continuing
      symptoms is overwhelming. There is a need for further research using agreed
      definitions, structured approaches and a full range of investigations in patients
      with difficult asthma.

PMID- 16105157
TI  - Mannose-binding lectin: biology and clinical implications.
AB  - The innate host defence molecule mannose-binding lectin (MBL) has attracted great
      interest as a potential candidate for passive immunotherapy to prevent infection.
      MBL is a multimeric lectin that recognizes a wide array of pathogens
      independently of specific antibody, and initiates the lectin pathway of
      complement activation. The basic structural unit is a triple helix of MBL
      peptides, which aggregate into complement-fixing higher-order structures
      (tetramers, pentamers and hexamers). The gene encoding MBL, MBL2, contains
      several common polymorphisms that influence transcription and assembly of the
      molecule into multimers. MBL2 coding alleles associated with low blood levels are
      present in up to 40% of Caucasoids, with up to 8% having genotypes associated
      with profound reduction in circulating MBL levels. Low-producing MBL2 variants
      and low MBL levels are associated with increased susceptibility to and severity
      of a variety of infective illnesses, particularly when immunity is already
      compromised--for example, in infants and young children, patients with cystic
      fibrosis, and after chemotherapy and transplantation. These observations suggest
      that administration of recombinant or purified MBL may be of benefit in clinical
      settings where MBL deficiency is associated with a high burden of infection. This
      review provides a background to MBL biology and disease associations, and
      identifies the exciting therapeutic possibilities of MBL replacement.

PMID- 16105158
TI  - Transjugular liver biopsy is a safe and effective intervention to guide
      management for patients with a congenital bleeding disorder infected with
      hepatitis C.
AB  - The prevalence of hepatitis C virus (HCV) infection in adult patients with a
      congenital bleeding disorder (CBD) approaches 95% and is a major cause of
      morbidity and mortality. Histological examination of the liver remains the
      cornerstone of management decisions in patients without a CBD. The reluctance to
      perform liver biopsies in patients with a CBD has been a major limitation in the
      management of these patients. We are currently the only haemophilia centre in
      Australasia performing liver biopsies in patients with a CBD for the purpose of
      guiding prognostic and therapeutic decisions. We report here the results of our
      centre's experience with transjugular liver biopsy (TJLB) in patients with a CBD.
      An adequate specimen for histological assessment was attained from all of the
      patients. There were no major complications recorded. Patients were hospitalized
      for < or = 48 h for haemostasis prophylaxis. The diagnostic specimen obtained
      from patients was integral in guiding their future management. We suggest that
      with a coordinated multidisciplinary approach, TJLB can be performed in patients
      with a CBD.

PMID- 16105159
TI  - Use of a quantitative point-of-care test for the detection of serum cardiac
      troponin T in patients with suspected acute coronary syndromes.
AB  - We compared a third generation quantitative cardiac troponin T (cTnT) point-of
      care testing (POCT) from Roche Diagnostics with the laboratory assay (Roche
      Elecsys 2010 immunoassay analyser). Heparin-treated blood and serum were
      collected simultaneously in 133 unselected patients (mean age 62 +/- 14 years,
      38% females) presenting to our hospital with possible cardiac chest pain. Results
      of the POCT were measured against the laboratory-based assay considered as the
      gold standard. There were 18 POCT positive versus 24 laboratory assay positive (>
      or = 0.03 ng/mL) patients. POCT was falsely negative in six patients, with values
      between 0.03 and 0.1 ng/mL. The POCT had a sensitivity of 75%, specificity of
      100%, positive predictive value of 100%, negative predictive value of 95% and a
      total accuracy of 95%; kappa = 0.831 (P < 0.001). There was good correlation
      between the values of POCT and the laboratory assay: Y = 1.195X + 0.002, r2 =
      0.94 (P < 0.0001). Whereas cTnT levels > 0.1 mg/mL were reliably detected with
      this current generation of POCT, cTnT levels between 0.03 and 0.10 ng/mL were
      not. Future generations of devices will need to improve sensitivity to reliably
      risk stratify patients with suspected acute coronary syndromes.

PMID- 16105160
TI  - From advance directives to advance care planning: current legal status, ethical
      rationales and a new research agenda.
AB  - This paper uses a case example to review the current legal status of advance
      directives, as well as their ethical rationale. We draw attention to ongoing
      efforts to institutionalize advance directives, and to some of the tractable and
      intractable reasons why advance directives are ineffective. We then introduce the
      concept of advance care planning, and argue that we should not assume that
      advance care directives have a place in this process. We conclude by offering
      three reasons why this assumption may operate, and by suggesting that contingency
      and uncertainty may sometimes overwhelm all rational approaches to medical care.

PMID- 16105161
TI  - Retropharyngeal abscess presenting with meningism.

PMID- 16105162
TI  - Two cases of intravascular lymphoma: highlighting the diagnostic difficulties in
      pyrexia of unknown origin.

PMID- 16105163
TI  - Azathioprine pancreatitis in inflammatory bowel disease and successful subsequent
      treatment with mercaptopurine.

PMID- 16105164
TI  - Spontaneous bruising as a possible adverse reaction to memantine.

PMID- 16105165
TI  - Hyperkalaemia with cyclooxygenase-2 inhibition and hypoaldosteronism.

PMID- 16105167
TI  - Stem cell research.

PMID- 16105169
TI  - Can't cope with 'acopia'.

PMID- 16105170
TI  - Incidence of asthma and mortality in a cohort of young adults: a 7-year
      prospective study.
AB  - BACKGROUND: Few longitudinal data exist on the incidence of asthma in young
      adults and on the overall mortality risk due to asthma. A 7-year follow-up
      prospective study was performed to assess the incidence of asthma and mortality
      from all causes in a cohort of young adults. METHODS: The life status of a cohort
      of 6031 subjects, aged 20-44 years, who replied to a respiratory screening
      questionnaire between 1991 and 1992, was ascertained in 1999. A new questionnaire
      investigating the history of asthma was subsequently sent to the 5236 subjects
      who were still alive and residents in the areas of the study. 3880 subjects (74%)
      replied to the second questionnaire. RESULTS: The incidence of adult-onset asthma
      was 15.3/10,000/year (95%CI: 11.2-20.8). The presence of asthma-like symptoms
      (IRR: 4.17; 95%CI: 2.20-7.87) and allergic rhinitis (IRR: 3.30; 95%CI: 1.71-6.36)
      at baseline were independent predictors of the onset of asthma, which was more
      frequent in women (IRR: 2.32; 95%CI: 1.16-4.67) and increased in the younger
      generations. The subjects who reported asthma attacks or nocturnal asthma
      symptoms at baseline had an excess mortality risk from all causes (SMR = 2.05;
      95%CI: 1.06-3.58) in the subsequent seven years. The excess mortality was mainly
      due to causes not related to respiratory diseases. CONCLUSION: Asthma occurrence
      is a relevant public health problem even in young adults. The likelihood of
      developing adult onset asthma is significantly higher in people suffering from
      allergic rhinitis, in women and in more recent generations. The presence of
      asthma attacks and nocturnal symptoms seems to be associated with a potential
      excess risk of all causes mortality.

PMID- 16105171
TI  - Absence of pathogenic mitochondrial DNA mutations in mouse brain tumors.
AB  - BACKGROUND: Somatic mutations in the mitochondrial genome occur in numerous tumor
      types including brain tumors. These mutations are generally found in the
      hypervariable regions I and II of the displacement loop and unlikely alter
      mitochondrial function. Two hypervariable regions of mononucleotide repeats occur
      in the mouse mitochondrial genome, i.e., the origin of replication of the light
      strand (OL) and the Arg tRNA. METHODS: In this study we examined the entire
      mitochondrial genome in a series of chemically induced brain tumors in the
      C57BL/6J strain and spontaneous brain tumors in the VM mouse strain. The tumor
      mtDNA was compared to that of mtDNA in brain mitochondrial populations from the
      corresponding syngeneic mouse host strain. RESULTS: Direct sequencing revealed a
      few homoplasmic base pair insertions, deletions, and substitutions in the tumor
      cells mainly in regions of mononucleotide repeats. A heteroplasmic mutation in
      the 16srRNA gene was detected in a spontaneous metastatic VM brain tumor.
      CONCLUSION: None of the mutations were considered pathogenic, indicating that
      mtDNA somatic mutations do not likely contribute to the initiation or progression
      of these diverse mouse brain tumors.

PMID- 16105172
TI  - The Ramachandran plots of glycine and pre-proline.
AB  - BACKGROUND: The Ramachandran plot is a fundamental tool in the analysis of
      protein structures. Of the 4 basic types of Ramachandran plots, the interactions
      that determine the generic and proline Ramachandran plots are well understood.
      The interactions of the glycine and pre-proline Ramachandran plots are not.
      RESULTS: In glycine, the psi angle is typically clustered at psi = 180 degrees
      and psi = 0 degrees. We show that these clusters correspond to conformations
      where either the N(i+1) or O atom is sandwiched between the two Halpha atoms of
      glycine. We show that the shape of the 5 distinct regions of density (the alpha,
      alphaL, betaS, betaP and betaPR regions) can be reproduced with electrostatic
      dipole-dipole interactions. In pre-proline, we analyse the origin of the zeta
      region of the Ramachandran plot, a region unique to pre-proline. We show that it
      is stabilized by a CO(i-1)...CdeltaHdelta(i+1) weak hydrogen bond. This is
      analogous to the CO(i-1)...NH(i+1) hydrogen bond that stabilizes the gamma region
      in the generic Ramachandran plot. CONCLUSION: We have identified the specific
      interactions that affect the backbone of glycine and pre-proline. Knowledge of
      these interactions will improve current force-fields, and help understand
      structural motifs containing these residues.

PMID- 16105173
TI  - Mimivirus relatives in the Sargasso sea.
AB  - The discovery and genome analysis of Acanthamoeba polyphaga Mimivirus, the
      largest known DNA virus, challenged much of the accepted dogma regarding viruses.
      Its particle size (>400 nm), genome length (1.2 million bp) and huge gene
      repertoire (911 protein coding genes) all contribute to blur the established
      boundaries between viruses and the smallest parasitic cellular organisms.
      Phylogenetic analyses also suggested that the Mimivirus lineage could have
      emerged prior to the individualization of cellular organisms from the three
      established domains, triggering a debate that can only be resolved by generating
      and analyzing more data. The next step is then to seek some evidence that
      Mimivirus is not the only representative of its kind and determine where to look
      for new Mimiviridae. An exhaustive similarity search of all Mimivirus predicted
      proteins against all publicly available sequences identified many of their
      closest homologues among the Sargasso Sea environmental sequences. Subsequent
      phylogenetic analyses suggested that unknown large viruses evolutionarily closer
      to Mimivirus than to any presently characterized species exist in abundance in
      the Sargasso Sea. Their isolation and genome sequencing could prove invaluable in
      understanding the origin and diversity of large DNA viruses, and shed some light
      on the role they eventually played in the emergence of eukaryotes.

PMID- 16105174
TI  - Successful myomectomy during pregnancy: a case report.
AB  - BACKGROUND: The medical literature has reported an increase in myomectomy during
      caesarean section in the past decade. However, myomectomy performed during
      pregnancy remains a rarity. The management of uterine fibroids during pregnancy
      is usually expectant and surgical removal is generally delayed until after
      delivery. We present a case of a large, symptomatic uterine fibroid diagnosed
      during pregnancy which was successfully managed by antepartum myomectomy. CASE
      PRESENTATION: A 30 year old woman presented with a one year history of abdominal
      swelling, amenorrhea and severe epigastric discomfort of 19 weeks duration. The
      abdomen was grossly distended and tense. A sonographic diagnosis of ovarian tumor
      in pregnancy was made. Laparotomy revealed a 32 cm degenerating subserosal
      uterine fibroid co-existing with an intrauterine pregnancy. Myomectomy was
      successfully performed. The subsequent antenatal period was uneventful with a
      spontaneous vaginal delivery of a female baby at 38 weeks. CONCLUSION: This
      report supports other studies and case series that have demonstrated the safety
      of myomectomy during pregnancy in selected circumstances.

PMID- 16105175
TI  - Development of an in vitro cleavage assay system to examine vaccinia virus I7L
      cysteine proteinase activity.
AB  - Through the use of transient expression assays and directed genetics, the
      vaccinia virus (VV) I7L gene product has been implicated as the major
      maturational proteinase required for viral core protein cleavage to occur during
      virion assembly. To confirm this hypothesis and to enable a biochemical
      examination of the I7L cysteine proteinase, an in vitro cleavage assay was
      developed. Using extracts of VV infected cells as the source of enzyme, reaction
      conditions were developed which allowed accurate and efficient cleavage of
      exogenously added core protein precursors (P4a, P4b and P25K). The cleavage
      reaction proceeded in a time-dependent manner and was optimal when incubated at
      25 degrees C. I7L-mediated cleavage was not affected by selected inhibitors of
      metalloproteinases, aspartic acid proteinases or serine proteinases (EDTA,
      pepstatin, and PMSF, respectively), but was sensitive to several general cysteine
      proteinase inhibitors (E-64, EST, Iodoacetic acid, and NEM) as well as the I7L
      active site inhibitor TTP-6171 [C. Byrd et al., J. Virol. 78:12147-12156 (2004)].
      Finally, in antibody pull down experiments, it could be demonstrated that
      monospecific alphaI7L serum depleted the enzyme activity whereas control sera
      including alphaG1L, directed against the VV metalloproteinase, did not. Taken
      together, these data provide biochemical evidence that I7L is a cysteine
      proteinase which is directly involved in VV core protein cleavage. Furthermore,
      establishment of this I7L-mediated in vitro cleavage assay should enable future
      studies into the enzymology and co-factor requirements of the proteolysis
      reaction, and facilitate antiviral drug development against this essential
      target.

PMID- 16105176
TI  - Interaction preferences across protein-protein interfaces of obligatory and non
      obligatory components are different.
AB  - BACKGROUND: A polypeptide chain of a protein-protein complex is said to be
      obligatory if it is bound to another chain throughout its functional lifetime.
      Such a chain might not adopt the native fold in the unbound form. A non
      obligatory polypeptide chain associates with another chain and dissociates upon
      molecular stimulus. Although conformational changes at the interaction interface
      are expected, the overall 3-D structure of the non-obligatory chain is unaltered.
      The present study focuses on protein-protein complexes to understand further the
      differences between obligatory and non-obligatory interfaces. RESULTS: A non
      obligatory chain in a complex of known 3-D structure is recognized by its stable
      existence with same fold in the bound and unbound forms. On the contrary, an
      obligatory chain is detected by its existence only in the bound form with no
      evidence for the native-like fold of the chain in the unbound form. Various
      interfacial properties of a large number of complexes of known 3-D structures
      thus classified are comparatively analyzed with an aim to identify structural
      descriptors that distinguish these two types of interfaces. We report that the
      interaction patterns across the interfaces of obligatory and non-obligatory
      components are different and contacts made by obligatory chains are predominantly
      non-polar. The obligatory chains have a higher number of contacts per interface
      (20 +/- 14 contacts per interface) than non-obligatory chains (13 +/- 6 contacts
      per interface). The involvement of main chain atoms is higher in the case of
      obligatory chains (16.9 %) compared to non-obligatory chains (11.2 %). The beta
      sheet formation across the subunits is observed only among obligatory protein
      chains in the dataset. Apart from these, other features like residue preferences
      and interface area produce marginal differences and they may be considered
      collectively while distinguishing the two types of interfaces. CONCLUSION: These
      results can be useful in distinguishing the two types of interfaces observed in
      structures determined in large-scale in the structural genomics initiatives,
      especially for those multi-component protein assemblies for which the biochemical
      characterization is incomplete.

PMID- 16105177
TI  - PHSkb: a knowledgebase to support notifiable disease surveillance.
AB  - BACKGROUND: Notifiable disease surveillance in the United States is predominantly
      a passive process that is often limited by poor timeliness and low sensitivity.
      Interoperable tools are needed that interact more seamlessly with existing
      clinical and laboratory data to improve notifiable disease surveillance.
      DESCRIPTION: The Public Health Surveillance Knowledgebase (PHSkb) is a computer
      database designed to provide quick, easy access to domain knowledge regarding
      notifiable diseases and conditions in the United States. The database was
      developed using Protege ontology and knowledgebase editing software. Data
      regarding the notifiable disease domain were collected via a comprehensive review
      of state health department websites and integrated with other information used to
      support the National Notifiable Diseases Surveillance System (NNDSS). Domain
      concepts were harmonized, wherever possible, to existing vocabulary standards.
      The knowledgebase can be used: 1) as the basis for a controlled vocabulary of
      reportable conditions needed for data aggregation in public health surveillance
      systems; 2) to provide queriable domain knowledge for public health surveillance
      partners; 3) to facilitate more automated case detection and surveillance
      decision support as a reusable component in an architecture for intelligent
      clinical, laboratory, and public health surveillance information systems.
      CONCLUSIONS: The PHSkb provides an extensible, interoperable system architecture
      component to support notifiable disease surveillance. Further development and
      testing of this resource is needed.

PMID- 16105178
TI  - Identifying inaccuracies on emergency medicine residency applications.
AB  - BACKGROUND: Previous trials have showed a 10-30% rate of inaccuracies on
      applications to individual residency programs. No studies have attempted to
      corroborate this on a national level. Attempts by residency programs to diminish
      the frequency of inaccuracies on applications have not been reported. We seek to
      clarify the national incidence of inaccuracies on applications to emergency
      medicine residency programs. METHODS: This is a multi-center, single-blinded,
      randomized, cohort study of all applicants from LCME accredited schools to
      involved EM residency programs. Applications were randomly selected to
      investigate claims of AOA election, advanced degrees and publications. Errors
      were reported to applicants' deans and the NRMP. RESULTS: Nine residencies
      reviewed 493 applications (28.6% of all applicants who applied to any EM
      program). 56 applications (11.4%, 95%CI 8.6-14.2%) contained at least one error.
      Excluding "benign" errors, 9.8% (95% CI 7.2-12.4%), contained at least one error.
      41% (95% CI 35.0-47.0%) of all publications contained an error. All AOA
      membership claims were verified, but 13.7% (95%CI 4.4-23.1%) of claimed advanced
      degrees were inaccurate. Inter-rater reliability of evaluations was good.
      Investigators were reluctant to notify applicants' dean's offices and the NRMP.
      CONCLUSION: This is the largest study to date of accuracy on application for
      residency and the first such multi-centered trial. High rates of incorrect data
      were found on applications. This data will serve as a baseline for future years
      of the project, with emphasis on reporting inaccuracies and warning applicants of
      the project's goals.

PMID- 16105179
TI  - International Committee on Taxonomy of Viruses and the 3,142 unassigned species.
AB  - In 2005, ICTV (International Committee on Taxonomy of Viruses), the official body
      of the Virology Division of the International Union of Microbiological Societies
      responsible for naming and classifying viruses, will publish its latest report,
      the state of the art in virus nomenclature and taxonomy. The book lists more than
      6,000 viruses classified in 1,950 species and in more than 391 different higher
      taxa. However, GenBank contains a staggering additional 3,142 "species"
      unaccounted for by the ICTV report. This paper reviews the reasons for such a
      situation and suggests what might be done in the near future to remedy this
      problem, particularly in light of the potential for a ten-fold increase in virus
      sequencing in the coming years that would generate many unclassified viruses. A
      number of changes could be made both at ICTV and GenBank to better handle virus
      taxonomy and classification in the future.

PMID- 16105180
TI  - Collection of population-based cancer staging information in Western Australia--a
      feasibility study.
AB  - BACKGROUND: Routine data from cancer registries often lack information on stage
      of cancer, limiting their use. This study aimed to determine whether or not it is
      feasible to add cancer staging data to the routine data collections of a
      population-based Western Australian Cancer Registry (WACR). METHODS: For each of
      the five most common cancer types (prostate, colorectal, melanoma, breast and
      lung cancers), 60 cases were selected for staging. For the 15 next most common
      cancer types, 20 cases were selected. Four sources for collecting staging data
      were used in the following order: the WACR, the hospital based cancer registries
      (HBCRs), hospital medical records, and letters to treating doctors. If the case
      was unable to be fully staged, due to lack of information on regional lymph node
      invasion or distant metastases, we made the following assumptions. Cases which
      had data available for tumour (T) and regional lymph nodes (N), but no assessment
      of distant metastasis (MX) were assumed to have no distant metastases (M0). Cases
      which had data for T and M, but no assessment of regional nodal involvement (NX)
      were assumed to have no regional nodal involvement (N0). RESULTS: The main focus
      of this project was the process of collecting staging data, and not the outcomes.
      For ovary, cervix and uterus cancers the existence of a HBCR increased the
      stageable proportion of cases so that staging data for these cancers could be
      incorporated into the WACR immediately. Breast and colorectal cancer could also
      be staged with adequate completeness if it were assumed that MX = M0. Similarly,
      melanoma and prostate cancer could be staged adequately if it were assumed that
      NX = N0 and MX = M0. Some cases of stomach, lung, pancreas, thyroid, testis and
      kidney cancers could be staged, but additional clinical input--on pathology
      request forms, for example--would be required to achieve useable levels of
      completeness. For the remaining cancer types either staging is widely regarded as
      not relevant, and no generally-accepted system exists, or an acceptable level of
      completeness is not achievable. CONCLUSION: Adding stage to routinely collected
      information in a cancer registry is possible for many cancer types, particularly
      if the assumptions regarding missing data are found to be acceptable or if the
      guidelines for MX = M0 assumptions are clarified. These findings should be
      generalizable to most cancer registries in developed countries, if hospital-based
      cancer registries or other specialized databases are accessible.

PMID- 16105181
TI  - Is microsporidial keratitis an emerging cause of stromal keratitis? A case series
      study.
AB  - BACKGROUND: Microsporidial keratitis is a rare cause of stromal keratitis. We
      present a series of five cases of microsporidial keratitis from a single centre
      in southern India with microbiologic and histopathologic features. CASE
      PRESENTATION: Patient charts of five cases of microsporidial stromal keratitis
      diagnosed between January 2002 and June 2004 were reviewed retrospectively for
      clinical data, microbiologic and histopathologic data. The presence of
      microsporidia was confirmed by special stains on corneal scrapings and/or corneal
      tissues, and electron microscopy. All patients were immunocompetent with a
      preceding history of trauma in three. Four patients presented with unilateral,
      small, persisting deep stromal infiltrates, of uncertain etiology, in the cornea,
      which were not responding to conventional antimicrobial treatment and required
      penetrating keratoplasty in three. Fifth case was unsuspected and underwent
      keratoplasty for post-traumatic scar. Three of five cases were diagnosed on
      corneal scrapings, prior to keratoplasty, while two were diagnosed only on
      histology. The microsporidia appeared as oval well defined bodies with dense
      staining at one pole. None of the patients showed recurrence following
      keratoplasty. CONCLUSION: Microsporidia, though rare, should be suspected in
      chronic culture-negative stromal keratitis. Organisms could lie dormant without
      associated inflammation.

PMID- 16105182
TI  - Bilateral neuro-retinitis following chick embryo cell anti-rabies vaccination--a
      case report.
AB  - BACKGROUND: The Optic nerve is rarely involved after sheep brain anti-rabies
      vaccination in the form of retrobulbar neuritis or papillitis. Bilateral
      neuroretinitis after chick embryo cell antirabies vaccination has not been
      reported. CASE PRESENTATION: We report the case of a 56 year old male who
      developed bilateral neuro-retinitis following three injections of antirabies
      vaccine prepared from the chick embryo. CONCLUSION: The chick embryo cell
      antirabies vaccine can cause bilateral neuroretinits which has not been reported
      previously.

PMID- 16105183
TI  - HEGPOL: randomized, placebo controlled, multicenter, double-blind clinical trial
      to investigate hepatoprotective effects of glycine in the postoperative phase of
      liver transplantation [ISRCTN69350312].
AB  - BACKGROUND: Kupffer cell-dependent ischemia/reperfusion (I/R) injury after liver
      transplantation is still of high clinical relevance, as it is strongly associated
      with primary dysfunction and primary nonfunction of the graft. Glycine, a non
      toxic, non-essential amino acid has been conclusively shown in various
      experiments to prevent both activation of Kupffer cells and reperfusion injury.
      Based on both experimental and preliminary clinical data this study protocol was
      designed to further evaluate the early effect of glycine after liver
      transplantation. METHODS/DESIGN: A prospective double-blinded randomized placebo
      controlled multicenter study with two parallel groups in a total of 130 liver
      transplant recipients was designed to assess the effect of multiple intravenous
      doses of glycine after transplantation. Primary endpoints in hierarchical order
      are: peak levels of both aspartat-amino-transaminase (AST) and alanine-amino
      transaminase (ALT) as surrogates for the progression of liver related injury, as
      well as both graft and patient survival up to 2 years after transplantation.
      Furthermore, the effect of glycine on cyclosporine A-induced nephrotoxicity is
      evaluated. DISCUSSION: The ongoing clinical trial represents an advanced element
      of the research chain, along which a scientific hypothesis has to go by, in order
      to reach the highest level of evidence; a randomized, prospective, controlled
      double-blinded clinical trial. If the data of this ongoing research project
      confirm prior findings, glycine would improve the general outcome after liver
      transplantation.

PMID- 16105184
TI  - Cytokine release from alveolar macrophages exposed to ambient particulate matter:
      heterogeneity in relation to size, city and season.
AB  - BACKGROUND: Several studies have demonstrated an association between exposure to
      ambient particulate matter (PM) and respiratory and cardiovascular diseases.
      Inflammation seems to play an important role in the observed health effects.
      However, the predominant particle component(s) that drives the inflammation is
      still not fully clarified. In this study representative coarse (2.5-10 microm)
      and fine (0.1-2.5 microm) particulate samples from a western, an eastern, a
      northern and a southern European city (Amsterdam, Lodz, Oslo and Rome) were
      collected during three seasons (spring, summer and winter). All fractions were
      investigated with respect to cytokine-inducing potential in primary macrophages
      isolated from rat lung. The results were related to the physical and chemical
      parameters of the samples in order to disclose possible connections between
      inflammatory potential and specific characteristics of the particles. RESULTS:
      Compared on a gram-by gram basis, both site-specific and seasonal variations in
      the PM-induced cytokine responses were demonstrated. The samples collected in the
      eastern (Lodz) and southern (Rome) cities appeared to be the most potent.
      Seasonal variation was most obvious with the samples from Lodz, with the highest
      responses induced by the spring and summer samples. The site-specific or seasonal
      variation in cytokine release could not be attributed to variations in any of the
      chemical parameters. Coarse fractions from all cities were more potent to induce
      the inflammatory cytokines interleukin-6 and tumour necrosis factor-alpha than
      the corresponding fine fractions. Higher levels of specific elements such as iron
      and copper, some polycyclic aromatic hydrocarbons (PAHs) and
      endotoxin/lipopolysaccaride seemed to be prevalent in the coarse fractions.
      However, variations in the content of these components did not reflect the
      variation in cytokine release induced by the different coarse fractions. Addition
      of polymyxin B did not affect the particle-induced cytokine release, indicating
      that the variations in potency among the coarse fractions are not explained by
      endootoxin. CONCLUSION: The inflammatory potential of ambient PM demonstrated
      heterogeneity in relation to city and season. The coarse particle fractions were
      consistently more potent than the respective fine fractions. Though a higher
      level of some elements, PAH and endotoxin was found in the coarse fractions, the
      presence of specific components was not sufficient to explain all variations in
      PM-induced cytokine release.

PMID- 16105185
TI  - Screening for sexually transmitted diseases in non-traditional settings: a
      personal view.
AB  - We conducted a literature search to review studies that presented quantitative
      data on sexually transmitted disease (STD) screening in non-traditional settings
      in the United States. We examined the studies for evidence of the feasibility of
      screening, population size reached, acceptability, yield, and potential for
      contributing to STD control. We found 17 studies in jails, eight in emergency
      room, five in schools and 15 in other community settings. Jail-based and
      emergency room-based STD screenings have the highest yields and the largest
      numbers screened and thus hold significant promise as settings for routine STD
      screening. More research needs to be done in school and community settings to
      better identify their potential.

PMID- 16105186
TI  - Prevalence and incidence of human papillomavirus infection in women in the USA: a
      systematic review.
AB  - A systematic review of studies published in the last decade was conducted to
      summarize data on the epidemiology of human papillomavirus (HPV) in the USA. A
      structured protocol was used to screen studies for review. Studies had to meet
      the following criteria: (1) the study was conducted in the USA, (2) the study
      population was predominantly adolescent women, (3) the description of the study's
      methodological and statistical methods is provided, and (4) the prevalence and/or
      incidence of HPV were clearly stated. The prevalence of HPV reported in the
      assessed studies ranged from 14% to more than 90%. The highest prevalence of HPV
      was identified among women attending sexually transmitted diseases (STD) clinics
      and college students, identifying them as target populations for prevention
      interventions. Conversely, the lowest HPV prevalence was among women in the
      general population. The review also revealed that HPV prevalence in African
      Americans is understudied, and the results of a few studies in this area are
      inconclusive.

PMID- 16105187
TI  - Thrombotic thrombocytopaenic purpura in HIV-infected patients.
AB  - Thrombotic thrombocytopaenic purpura (TTP) results from deficiency of von
      Willebrand factor-cleaving protease (vWF-cp) activity. Eight HIV-infected
      patients presented with TTP, representing 12.5% of all TTP treated at this
      centre. In four patients presentation with TTP revealed underlying HIV infection,
      the other four patients were previously known to be HIV infected, with plasma
      exchange and highly active antiretroviral therapy (HAART) all recovered.
      Normalization of vWF-cp activity was associated with recovery. Relapse occurred
      in two patients who discontinued HAART against medical advice, suggesting that
      HIV has a causal role in this condition. Given the clear benefit from HAART in
      addition to plasma exchange, these data suggest that all patients presenting with
      TTP should undergo HIV testing.

PMID- 16105188
TI  - Issues related to gay and bisexual men's acceptance of a future AIDS vaccine.
AB  - The purpose of this study was to identify the salient issues related to getting a
      future AIDS vaccine among a high-risk group. In-depth interviews were conducted
      with 24 White and Black men who have sex with men (MSM). Participants reported
      that they would need information regarding the vaccine strategy, the clinical
      trials research, and vaccine attributes. A prerequisite for Black participants
      was the prior inclusion of Blacks in clinical trials. A high degree of safety and
      effectiveness, minimal side-effects, high-perceived risk, and affordable cost
      would promote vaccine acceptance. Barriers were low degree of safety and
      effectiveness, harsh side-effects, low-perceived risk, perception of a backlash
      effect, cost, and inconvenience. MSM may not readily get an AIDS vaccine unless
      they are provided with specific details and the benefits outweigh the costs.
      Researchers conducting HIV vaccine trials should provide information about the
      research and insure that samples represent Black men.

PMID- 16105189
TI  - The prevalence of abnormal cervical cytology in a sexually transmitted diseases
      clinic.
AB  - Women seeking sexually transmitted disease (STD) services are at high risk of
      human papillomavirus infections. Cervical cytological screening with Papanicolau
      staining (Pap smear) is not consistently offered at public STD clinics. We
      reviewed Pap smear results on a series of 1000 female STD clinic attendees,
      abstracted demographics, risk behaviours and STD diagnosis from the clinical
      record and tested for associations with abnormal Pap smear. In all, 5.7% of the
      satisfactory specimens (56/993) were abnormal; increasing age category, genital
      warts, and chlamydia infections were independently associated with an abnormal
      Pap smear in multivariate analysis. Routine Pap smear screening provided
      satisfactory results in the STD clinic and, where population-based programmes are
      not available, should be fully integrated into public STD care, (particularly in
      settings serving younger women).

PMID- 16105190
TI  - Feasibility of voluntary counselling and testing services for HIV among pregnant
      women presenting in labour in Pune, India.
AB  - Factors affecting the eligibility and acceptability of voluntary counselling and
      rapid HIV testing (VCT) were examined among pregnant women presenting in labour
      in Pune, India. Of the 6702 total women appearing at the delivery room from April
      2001 to March 2002, 4638 (69%) were admitted for normal delivery. The remaining
      women presented with obstetrical complications, delivered immediately or were
      detected to be in false labour. Overall, 2818 (61%) of the admitted women had
      been previously tested for HIV during their pregnancy. If previously seen in the
      hospital's affiliated antenatal clinic, the likelihood of being previously tested
      was 89%, in contrast to 27% of women having prenatal care elsewhere. Of the
      admitted women, 3436 (74.3%) were assessed for their eligibility for rapid HIV
      VCT in the delivery room. Only 1322 (38%) of these women were found to be in
      early labour and without severe pain or complications, and therefore eligible for
      rapid HIV screening in the delivery room (DR). Of those 1322 eligible women, only
      582 (44%) consented and were tested for HIV, of whom nine (1.6%) were found to be
      HIV-infected. Of the 1674 women arriving in the DR with no evidence of previous
      HIV testing, through this DR screening programme, we identified four women with
      HIV who could now benefit from treatment with ART. Given the high rates of HIV
      testing in the antenatal clinic at this site and the challenges inherent to
      conducting DR screening, alternatives such as post-partum testing should be
      considered to help reduce maternal to infant transmission in this population.

PMID- 16105191
TI  - Association between the intact foreskin and inferior standards of male genital
      hygiene behaviour: a cross-sectional study.
AB  - This study was undertaken to determine whether non-circumcised men have inferior
      standards of genital hygiene behaviour, as measured by reported washing of the
      whole penis, compared with circumcised men. Male attenders at a sexually
      transmitted infections (STI) clinic at Ealing Hospital, London had routine STI
      tests and examinations performed and were asked about the frequency and
      thoroughness of genital washing. One hundred and fifty non-circumcised and 75
      circumcised men were enrolled. Not always washing the whole penis, including
      retracting the foreskin in non-circumcised men every time they washed (defined as
      inferior genital hygiene behaviour) was more common in non-circumcised (26%) than
      circumcised men (4%) (crude odds ratio = 8.43, 95% confidence interval: 2.51
      28.3, P<0.001) and those with balanitis (42% and 5%, P=0.036). Circumcised men
      were more likely than non-circumcised men to wash the genital area more than once
      a day (37% and 19%, P=0.011). Studies investigating the relationship between male
      circumcision status and other outcomes, for example HIV infection, should include
      assessment of genital hygiene.

PMID- 16105192
TI  - Impact of an effective multidrug-resistant tuberculosis control programme in the
      setting of an immature HIV epidemic: system dynamics simulation model.
AB  - This study sought to determine the impact of an effective programme of multidrug
      resistant tuberculosis control (MDRTB) on a population that is witnessing an
      explosive HIV epidemic among injecting drug users (IDUs), where the prevalence of
      MDRTB is already high. A transmission model was constructed that represents the
      dynamics of the drug-susceptible tuberculosis (DSTB), MDRTB and HIV spread among
      the adult population of Samara Oblast, Russia: from official notifications of
      tuberculosis and of HIV infection, estimates of MDRTB derived from surveillance
      studies, population data from official regional statistics, data on transmission
      probabilities from peer-reviewed publications and informed estimates, and policy
      makers' estimates of IDU populations. Two scenarios of programme effectiveness
      for MDRTB were modelled and run over a period of 10 years to predict cumulative
      deaths. In a population of 3.3 million with a high prevalence of MDRTB, an
      emerging epidemic of HIV among IDUs, and a functioning directly observed therapy
      short course (DOTS) programme, the model predicts that under low cure rates for
      MDRTB the expected cumulative deaths from tuberculosis will reach 6303 deaths
      including 1900 deaths from MDRTB at 10 years. Under high cure rate for MDRTB 4465
      deaths will occur including 134 deaths from MDRTB. At 10 years there is little
      impact on HIV-infected populations from the MDRTB epidemic, but as the HIV
      epidemic matures the impact becomes substantial. When the model is extended to 20
      years cumulative deaths from MDRTB become very high if cure rates for MDRTB are
      low and cumulative deaths in the HIV-infected population, likewise, are
      profoundly affected. In the presence of an immature HIV epidemic failure to
      actively control MDRTB may result in approximately a third more deaths than if
      effective treatment is given. As the HIV epidemic matures then the impact of
      MDRTB grows substantially if MDRTB control strategies are ineffective. The
      epidemiological starting point for these scenarios is present in many regions
      within the former Soviet Union and this analysis suggests control of MDRTB should
      be an urgent priority.

PMID- 16105193
TI  - The impact of syphilis mass treatment one year later: self-reported behaviour
      change among participants.
AB  - In 2000, syphilis mass treatment using oral azithromycin was delivered to at-risk
      British Columbians during a sex trade-related outbreak. The initiative included
      education, counselling and referral. This cross-sectional, observational study
      examines knowledge, attitudes and self-reported behaviour after one year among
      mass treatment participants compared with eligible non-participants. Participants
      self-reported positive changes: reduction in sexual partners overall (P=0.001)
      and for sex workers (P<0.01), decrease in unprotected oral sex (P=0.03),
      knowledge of asymptomatic syphilis (P=0.02), positive attitudes to mass treatment
      (P=0.02) and to the street nurses (P=0.01). Increased awareness was associated
      with increased condom use for vaginal sex overall (P=0.02) and for sex workers
      (P=0.03) and increased condom use for oral sex (P=0.05). There was no difference
      in syphilis incidence. Syphilis outbreak interventions that include education,
      support and referral can result in long-term positive behaviour changes.

PMID- 16105194
TI  - Polymerase chain reaction for diagnosis of genital herpes: a missed opportunity?
AB  - This study audited the utilization of herpes simplex virus polymerase chain
      reaction (HSV PCR) in the investigation of recurrent anogenital ulceration at the
      Mortimer Market Centre. Clinic guidelines for use of HSV PCR were modified in
      April 2003 to expand PCR use. Ninety-six case-notes belonging to patients
      presenting with recurrent anogenital ulceration between 1 April and 16 October
      2003 were reviewed and 59 were suitable for inclusion. Details of the
      investigations carried out at each visit were recorded. HSV PCR was used
      according to guidelines in eight of the 59 cases studied. This audit showed under
      utilization of HSV PCR testing with poor adherence to clinic guidelines when
      cases of suspected recurrent genital herpes were investigated. This led to under
      diagnosis and delay in diagnosis. This audit stresses the importance of informing
      all clinical staff of the improved sensitivity and relative affordability of HSV
      PCR compared with HSV tissue culture.

PMID- 16105195
TI  - Fatal Kaposi's sarcoma-associated immune reconstitution following highly active
      antiretroviral therapy.

PMID- 16105196
TI  - Disclosure of antenatal HIV testing results.

PMID- 16105197
TI  - Sexual health guidance for GPs: the shortened version.

PMID- 16105199
TI  - Is the lack of interest in applications for SpR positions in genitourinary
      medicine a national problem or just a northern issue?

PMID- 16105204
TI  - Confocal Raman microscopy of liquid-crystal-filled polymer capsules made by photo
      enforced stratification.
AB  - The applicability of confocal Raman microscopy for characterizing thin liquid
      crystal (LC) filled polymer capsules obtained by photo-enforced stratification is
      demonstrated. The investigated structure consists of an array of polymer capsules
      (typical size 500 x 500 x 20 microm) filled with LC material and is made by
      photopolymerization of a mixture of monomers and LC. Such an array can be used as
      the electro-optical component in liquid crystal displays. Confocal Raman
      microscopy does not require complex sample preparation, is non-invasive, and is
      shown to have adequate spatial and depth resolution. Although Raman spectroscopy
      is inherently insensitive, the use of data preprocessing and computational
      modeling makes it possible to quantify both the conversion of monomer to polymer
      and the compositions of both the polymer-rich and the LC-rich phase.

PMID- 16105205
TI  - Investigation of the aqueous dissolution of semicrystalline poly(ethylene oxide)
      using infrared chemical imaging: the effects of molecular weight and
      crystallinity.
AB  - Fourier transform infrared (FT-IR) imaging was used to successfully explore
      several factors influencing the dissolution of poly(ethylene oxide). The effect
      of the degree of crystallinity on the rate of dissolution of mid-range molecular
      weight PEO was negligible over the temperature ranges studied. The influence of
      molecular weight on polymer dissolution was found to be much greater than the
      changes in morphology. An examination of the polymer and solvent images and
      absorbance profiles, compared with the results of the bulk polymer/solvent
      boundary movement, confirmed this relationship. An investigation of the bulk
      polymer/solvent boundary using a crystalline-sensitive polymer band showed the
      crystalline to amorphous phase change occurred over a short distance. Moreover,
      solvent diffusion ahead of the bulk polymer/solvent front was minimal, most
      likely a result of the required phase change, which in turn regulated the degree
      of solvent ingress. Modeling of the dissolution was performed using the Peppas
      (power law) model. Physical parameters of the dissolution process were obtained
      from fitting the release profiles to the power law (fraction released = k x t(n),
      where k is the dissolution rate constant and n is the release exponent). Results
      indicated the model worked well to describe dissolution at all molecular weights.
      By varying the number of data points input to the model and then comparing the
      generated graphs, it becomes clear that not only does the dissolution slow down
      over the course of the experiment, but an increase in molecular weight enhances
      this effect. The effect of different types of drug on the rate of polymer
      dissolution was also studied. The dissolution of neat polymer was compared to the
      dissolution of polymer containing 10% (by weight) of theophylline, etophylline,
      or testosterone. The general trend of all the dissolution curves was the same,
      with the addition of etophylline and testosterone tracing almost the same route
      in terms of movement of the bulk polymer/solvent front.

PMID- 16105206
TI  - Discrimination of nylon polymers using attenuated total reflection mid-infrared
      spectra and multivariate statistical techniques.
AB  - Nylons are an important class of synthetic polymers, from an industrial, as well
      as forensic, perspective. A spectroscopic method, such as Fourier transform
      infrared (FT-IR) spectroscopy, is necessary to determine the nylon subclasses (e.
      g., nylon 6 or nylon 6,6). Library searching using absolute difference and
      absolute derivative difference algorithms gives inconsistent results for
      identifying nylon subclasses. The objective of this study was to evaluate the
      usefulness of peak ratio analysis and multivariate statistics for the
      identification of nylon subclasses using attenuated total reflection (ATR)
      spectral data. Many nylon subclasses could not be distinguished by the peak ratio
      of the N-H vibrational stretch to the sp(3) C-H(2) vibrational stretch
      intensities. Linear discriminant analysis, however, provided a graphical
      visualization of differences between nylon subclasses and was able to correctly
      classify a set of 270 spectra from eight different subclasses with 98.5% cross
      validated accuracy.

PMID- 16105207
TI  - External reflection Fourier transform infrared spectroscopy of surfactants at the
      air-water interface: separation of bulk and adsorbed surfactant signals.
AB  - External reflection Fourier transform infrared spectroscopy (ERFTIRS) has been
      used to obtain spectra of monolayers of the hydrocarbon surfactant octaethylene
      glycol monodecyl ether (C(10)E(8)) and the fluorocarbon surfactant ammonium
      perfluorononanoate (APFN) at the expanding liquid surface of an overflowing
      cylinder. The use of target factor analysis (TFA) to separate out the
      contributions of water, adsorbed surfactant, and dissolved surfactant is
      demonstrated. For both surfactants, there is a linear relationship between the
      component weight of the adsorbed surfactant, obtained by TFA, and the surface
      excess determined independently by ellipsometry or neutron reflection. This
      linear relationship suggests that the monolayers behave like isotropic films with
      a constant density. A sensitivity of less than 10% of a monolayer is
      demonstrated. The benefits of using a multivariate curve fitting procedure to
      analyze sets of ER-FTIR spectra are discussed and some potential pitfalls are
      identified. This technique is also applicable to static interfaces.

PMID- 16105208
TI  - Characterization of infrared chemical sensors modified with ZnO nanowires for the
      detection of volatile organic compounds.
AB  - In this paper we describe the application and characterization of zinc oxide
      (ZnO) nanowires in an infrared (IR) chemical sensing system for the detection of
      volatile organic compounds (VOCs). Under suitable conditions, we grew ZnO
      nanowires on the surfaces of IR internal reflection elements (IREs) and obtained
      successful results for the detection of VOCs. ZnO nanowires offer a large surface
      area to effectively adsorb the examined species; the sensitivity of these IR
      sensing systems was increased by 3- to 15-fold after surface treatment with the
      ZnO nanowires. To explore the performance of this type of sensor, we correlated
      the morphologies of the ZnO nanowires grown on the surfaces of the IREs with the
      adsorption behavior observed during the sensing of the VOCs. To characterize the
      properties of the ZnO nanowires during the detection of VOCs having a range of
      functionalities, we classified the VOCs and examined their enrichment factors by
      comparing the IR signals detected in the presence and absence of the ZnO
      nanowires. Our results indicate that the ZnO nanowires exhibited better
      performance for the detection of aromatic-type VOCs than they did for non
      aromatic compounds. For quantitative analyses, we examined several compounds for
      their responses toward varying quantities of injected VOCs. Our results indicate
      that the IREs treated with ZnO nanowires display acceptable linearity in their
      standard curves; the linear regression coefficients were higher than 0.995 for a
      range of volatile compounds.

PMID- 16105209
TI  - Surface-enhanced micro-Raman detection and characterization of calix[4]arene
      polycyclic aromatic hydrocarbon host-guest complexes.
AB  - Surface-enhanced micro-Raman spectroscopy (micro-SERS) was used to detect traces
      of the hazardous pollutant polycyclic aromatic hydrocarbons (PAHs) pyrene and
      benzo[c]phenanthrene deposited onto a calix[4]arene-functionalized Ag colloidal
      surface. High spectral reproducibility and very low molecular detection limits
      (10(-8) M) were obtained by using 25,27-carboethoxy-26,28-hidroxy-p-tert
      butylcalix[4]arene as host molecule. Films of immobilized aggregated Ag
      nanoparticles, obtained by chemical reduction with hydroxylamine, were prepared
      by direct adhesion on a glass surface. The influence of the aggregation degree of
      the initial Ag nanoparticles on the micro-SERS detection effectiveness was
      checked. Different relative concentrations of the host (calixarene receptor) and
      the guest (PAHs) were attempted in order to optimize detection of the pollutant.
      The obtained results indicated that the detection limit is much lower in the case
      of benzo[c]phenanthrene than in pyrene when exciting with the 785 nm line of a
      diode laser. A detailed interpretation of the Raman spectra was accomplished in
      order to obtain more information about the interaction mechanism of the host
      guest complex, which could be useful in the future for the design of powerful
      detection systems.

PMID- 16105210
TI  - Surface-enhanced Raman spectroscopy of bacteria and pollen.
AB  - A technique for distinguishing biological material based on surface-enhanced
      Raman scattering (SERS) is reported in this work. Of particular interest is
      biological material that can be airborne. Silver colloidal particles with
      diameters in the range 10 to 20 nm and with a characteristic ultraviolet-visible
      (UV-VIS) absorption band at 400 nm were used to obtain SERS spectra of
      Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhimurium bacteria and
      a number of tree and grass pollens (Cupressus arizonica (cypress), Sequoia
      sempervirens (redwood), Populus deltoides (cottonwood), Poa pratensis (Kentucky
      bluegrass), and Anthoxanthum odoratum (sweet vernal grass)). While differences in
      the SERS spectra among the bacteria were small, we found that the pollen spectra
      we analyzed could readily be distinguished from the bacteria spectra, and there
      were significant differences between pollen from different families. In order to
      obtain reproducible results, we studied the parameters controlling the
      interaction between the analyte and the nanoscale metallic surface. Our results
      show that the volume ratio of analyte to colloidal particles must be within a
      narrow range of values to optimize the signal-to-noise ratio of the SERS spectra
      and minimize the fluorescence from the analyte. Also, we found that the time
      dependent behavior of colloidal/bacterial suspensions (or adsorption rate of the
      silver colloid particles on the bacteria) is strongly dependent on pH, density of
      bacteria in solution, and even, to some extent, the type of bacteria.

PMID- 16105211
TI  - Determination of glucose in human aqueous humor using Raman spectroscopy and
      designed-solution calibration.
AB  - Glucose concentrations of in vitro human aqueous humor (HAH) samples from
      cataract patients were determined using 785 nm Raman spectra and partial least
      squares (PLS) calibration. PLS models were created from spectra of prepared
      calibration solutions rather than aqueous humor samples. Spectra were obtained
      with an excitation energy (100 mW for 150 s), which was higher than can be
      applied in vivo, to decrease the models' contribution to prediction uncertainty.
      The solutions contained experimentally designed levels of glucose, bicarbonate,
      lactate, urea, and ascorbate. Multiplicative signal correction of spectra helped
      compensate for the +/-20% drift in laser power observed at the sample over six
      noncontiguous days of data collection. Seventeen HAH samples containing 38-775
      mg/dL of glucose exhibited a root-mean-square error (RMSEP) of 22 mg/dL,
      coefficient of determination (r(2)) of 0.989, and bias of 6 mg/dL when predicted
      from lower energy (30 s) spectra collected contemporaneously with fifty
      calibration spectra. Similar results were obtained even when spectral data were
      gathered separately for human aqueous humor samples and calibration samples: 10
      HAH samples, calibrated on 25 solutions measured 3.6 weeks earlier, exhibited an
      RMSEP of 23 mg/dL, r(2) of 0.992, and bias of 9 mg/dL. The results demonstrate
      progress toward the determination of glucose levels in patient-derived aqueous
      humor using laboratory-derived "artificial aqueous humor" calibration solutions.

PMID- 16105212
TI  - Spectrofluorimetry and chemometrics for investigation of norfloxacin distribution
      in multilamellar liposomes.
AB  - Norfloxacin (NFX), a fluoroquinolone, was encapsulated in multilamellar liposomes
      (MLV) of soy-bean phosphatidylcholine at pH 7.0. The observed affinity of this
      class of drugs for hydrophobic environments, such as phospholipid bilayers, could
      lead to a better understanding of the mechanism of uptake in bacteria. The
      fluorescent properties of NFX were examined both free in solution and in MLV,
      using anisotropy and fluorescence quenching measurements. The latter data was
      treated with a chemometric method to deconvolute the overlapped spectra of
      zwitterionic and neutral species of NFX in equilibrium at this pH. The results
      show that NFX incorporates into the lipidic bilayers with two different
      distributions of species: the zwitterionic form in the lipid/aqueous interface,
      and the neutral one, more towards the center of the bilayer.

PMID- 16105213
TI  - Fungus covered insulator materials studied with laser-induced fluorescence and
      principal component analysis.
AB  - A method combining laser-induced fluorescence and principal component analysis to
      detect and discriminate between algal and fungal growth on insulator materials
      has been studied. Eight fungal cultures and four insulator materials have been
      analyzed. Multivariate classifications were utilized to characterize the
      insulator material, and fungal growth could readily be distinguished from a clean
      surface. The results of the principal component analyses make it possible to
      distinguish between algae infected, fungi infected, and clean silicone rubber
      materials. The experiments were performed in the laboratory using a fiber-optic
      fluorosensor that consisted of a nitrogen laser and an optical multi-channel
      analyzer system.

PMID- 16105214
TI  - Spatially resolved stress analysis in Al2O3/3Y-TZP multilayered composite using
      confocal fluorescence spectroscopy.
AB  - Fluorescence piezo-spectroscopy (PS) was applied to evaluate the residual stress
      fields stored in a multilayered Al(2)O(3)/3Y-TZP (3 mol% Y(2)O(3)-stabilized
      ZrO(2)) composite using the chromophoric fluorescence spectra of Al(2)O(3). The
      PS results were compared with a theoretical stress distribution in the laminate,
      calculated according to a repeating unit cell model. However, in practical
      fluorescence spectroscopy, each measurement point corresponded to a finite volume
      of material, within which the scattered light experienced fluorescence
      wavelengths characteristic of the local (weight-average) stress fields. Because
      of the finite volume of material probed in PS measurements, a comparison between
      the experimental and calculated values requires that the calculated stresses be
      convoluted according to the depth-response function of the probe. A pinhole
      aperture incorporated in the Raman microprobe was used to control the collection
      probe depth and to modulate the portion of the whole fluorescence emission
      reaching the detector. According to calibrations of the probe depth and probe
      response function, probe-convoluted stresses were obtained and a spatially
      resolved mapping of residual stresses could be obtained.

PMID- 16105215
TI  - Phase-modulation fluorometer using a dynode-voltage burst-modulated
      photomultiplier tube.
AB  - We propose a new scheme for a phase-modulation fluorometer (PMF) in which a
      photomultiplier tube (PMT) is used as a photo detector whose gain is modulated
      sinusoidally with a burst signal of period T and duty ratio 0.5. The carrier wave
      of the burst modulation signal is synchronized with an incident fluorescence
      signal. In order to modulate the gain of the PMT, one of the dynodes in the PMT
      was deeply biased and the burst signal was superimposed. Because the fluorescence
      signal is converted to a direct current (dc) signal by the PMT internal
      modulation, we can make the value of the load resistance of the PMT relatively
      large under the condition tau < or = T/2, where tau is a time constant of a low
      pass filter attached to the output of the PMT. The proposed scheme brings about
      advantages in sensitivity and noise immunity in detecting weak fluorescence in
      comparison with those of the conventional PMF. The combined technique of the
      burst modulation of the gain of the PMT and the alternating current (ac) signal
      detection alleviates the influence of the background light.

PMID- 16105216
TI  - Prediction of potential mushroom yield by visible and near-infrared spectroscopy
      using fresh phase II compost.
AB  - Potential mushroom (Agaricus bisporus) yield of phase II compost is determined by
      interactions of key quality parameters including dry matter, nitrogen dry matter,
      ammonia, pH, conductivity, thermophilic microorganisms, C : N ratio, fiber
      fractions, ash, and certain minerals. This study was aimed at generating robust
      visible and near-infrared (Vis-NIR) calibrations for predicting potential yield,
      using spectra from fresh phase II compost. Four compost comparative trials were
      carried out during the winter and summer months of 2001-2003, under controlled
      experimental conditions employing six commercially prepared composts, with eight
      replicate (8 bag) plots per treatment (48 x 8 = 384). The substrates were
      prepared by windrow or bunker phase I, followed by phase II production. The fresh
      samples were scanned for Vis-NIR (400-2498 nm) spectra, averaged, transformed,
      and regressed against the recorded yield by employing a modified partial least
      squares algorithm. The best calibration model generated from the database
      explained 84% of yield variation within the data set with a standard error of
      calibration of 13.75 kg/tonne of fresh compost. The model was successfully tested
      for robustness with yield results obtained from a validation trial, carried out
      under similar experimental conditions in early 2004, and the standard error of
      prediction was 18.21 kg/tonne, which was slightly higher than the mean
      experimental error (17.94 kg/tonne) of the trial. The accuracy of the model is
      acceptable for estimating potential yield by classifying phase II substrate as
      poor (180-220 kg), medium (220-260 kg), and high (260-300 kg) yielding compost.
      The yield prediction model is being transferred to a new instrument based at
      Loughgall for routine evaluation of commercial phase II samples.

PMID- 16105217
TI  - New approach to avoid erroneous interpretation of results derived from
      generalized two-dimensional correlation analysis for applications in catalysis.
AB  - Surface characterization and catalysis can significantly benefit from the
      application of generalized two-dimensional (2D) correlation analysis. This two
      dimensional approach allows a better resolution of overlapping peaks, can reveal
      new features not readily observable in the raw spectra, gives clear evidence for
      spectral intensities that change as an effect of a perturbation applied to the
      system, and allows the establishment of time sequences for the changes occurring
      in different spectral features of interest for determining reaction intermediates
      and/or mechanisms. The interpretation of the synchronous and asynchronous plots
      was observed to lead to erroneous time sequences when spectral features change in
      a non-monotonic way, such as a biphasic or oscillatory behavior, under the
      influence of a perturbation. We propose a new approach to the 2D correlation
      analysis to avoid misinterpretation of the results calculated in the asynchronous
      plot. Progressive correlation analysis (ProCorA) calculates the synchronous plot
      from the first two spectra of the data matrix and one spectrum is added at every
      step of the analysis. The sequence of changes can be set up from the progressive
      evolution of peaks in both the synchronous and asynchronous plots.

PMID- 16105218
TI  - Improved dispersion of bacterial endospores for quantitative infrared sampling on
      gold coated porous alumina membranes.
AB  - An improved method for qualitative and quantitative sampling of bacterial
      endospores using Fourier transform infrared (FT-IR) microscopy on gold-coated
      porous alumina membranes is presented. Bacillus subtilis endospores were filtered
      onto gold-coated alumina membranes serving as substrates. Studies in the mid
      infrared (MIR) region revealed the characteristic bacterial absorption spectrum
      at low surface concentration, while scanning electron microscopy (SEM) images of
      the same samples provided precise calculation of the surface concentration of the
      bacterial endospores. Under the conditions of study, the average concentration of
      endospores was determined to be 1356 +/- 35 spores in a 100 x 100 mum(2) area,
      with a relative standard deviation of 0.0260. Examination of ten random spots on
      multiple substrates with FT-IR microscopy apertured to the same area gave an
      average relative standard deviation of 0.0482 in the signal strength of the amide
      A band at 3278 cm(-1). An extinction cross-section in reflection of sigma(ext) =
      (7.8 +/- 0.6) x 10(-9) cm(2)/endospore was calculated for the amide A band at the
      frequency of its peak absorbance, 3278 cm(-1). The absorption cross-section of
      the amide A band in reflection is estimated to be sigma(abs) approximately (2.10
      +/- 0.12) x 10(-9) cm(2)/endospore.

PMID- 16105219
TI  - Gradient-based adaptation of general gaussian kernels.
AB  - Gradient-based optimizing of gaussian kernel functions is considered. The
      gradient for the adaptation of scaling and rotation of the input space is
      computed to achieve invariance against linear transformations. This is done by
      using the exponential map as a parameterization of the kernel parameter manifold.
      By restricting the optimization to a constant trace subspace, the kernel size can
      be controlled. This is, for example, useful to prevent overfitting when
      minimizing radius-margin generalization performance measures. The concepts are
      demonstrated by training hard margin support vector machines on toy data.

PMID- 16105220
TI  - Learning only when necessary: better memories of correlated patterns in networks
      with bounded synapses.
AB  - Learning in a neuronal network is often thought of as a linear superposition of
      synaptic modifications induced by individual stimuli. However, since biological
      synapses are naturally bounded, a linear superposition would cause fast
      forgetting of previously acquired memories. Here we show that this forgetting can
      be avoided by introducing additional constraints on the synaptic and neural
      dynamics. We consider Hebbian plasticity of excitatory synapses. A synapse is
      modified only if the postsynaptic response does not match the desired output.
      With this learning rule, the original memory performances with unbounded weights
      are regained, provided that (1) there is some global inhibition, (2) the learning
      rate is small, and (3) the neurons can discriminate small differences in the
      total synaptic input (e.g., by making the neuronal threshold small compared to
      the total postsynaptic input). We prove in the form of a generalized perceptron
      convergence theorem that under these constraints, a neuron learns to classify any
      linearly separable set of patterns, including a wide class of highly correlated
      random patterns. During the learning process, excitation becomes roughly balanced
      by inhibition, and the neuron classifies the patterns on the basis of small
      differences around this balance. The fact that synapses saturate has the
      additional benefit that nonlinearly separable patterns, such as similar patterns
      with contradicting outputs, eventually generate a subthreshold response, and
      therefore silence neurons that cannot provide any information.

PMID- 16105221
TI  - Coding of temporally varying signals in networks of spiking neurons with global
      delayed feedback.
AB  - Oscillatory and synchronized neural activities are commonly found in the brain,
      and evidence suggests that many of them are caused by global feedback. Their
      mechanisms and roles in information processing have been discussed often using
      purely feedforward networks or recurrent networks with constant inputs. On the
      other hand, real recurrent neural networks are abundant and continually receive
      information-rich inputs from the outside environment or other parts of the brain.
      We examine how feedforward networks of spiking neurons with delayed global
      feedback process information about temporally changing inputs. We show that the
      network behavior is more synchronous as well as more correlated with and phase
      locked to the stimulus when the stimulus frequency is resonant with the inherent
      frequency of the neuron or that of the network oscillation generated by the
      feedback architecture. The two eigenmodes have distinct dynamical
      characteristics, which are supported by numerical simulations and by analytical
      arguments based on frequency response and bifurcation theory. This distinction is
      similar to the class I versus class II classification of single neurons according
      to the bifurcation from quiescence to periodic firing, and the two modes depend
      differently on system parameters. These two mechanisms may be associated with
      different types of information processing.

PMID- 16105222
TI  - Attention-gated reinforcement learning of internal representations for
      classification.
AB  - Animal learning is associated with changes in the efficacy of connections between
      neurons. The rules that govern this plasticity can be tested in neural networks.
      Rules that train neural networks to map stimuli onto outputs are given by
      supervised learning and reinforcement learning theories. Supervised learning is
      efficient but biologically implausible. In contrast, reinforcement learning is
      biologically plausible but comparatively inefficient. It lacks a mechanism that
      can identify units at early processing levels that play a decisive role in the
      stimulus-response mapping. Here we show that this so-called credit assignment
      problem can be solved by a new role for attention in learning. There are two
      factors in our new learning scheme that determine synaptic plasticity: (1) a
      reinforcement signal that is homogeneous across the network and depends on the
      amount of reward obtained after a trial, and (2) an attentional feedback signal
      from the output layer that limits plasticity to those units at earlier processing
      levels that are crucial for the stimulus-response mapping. The new scheme is
      called attention-gated reinforcement learning (AGREL). We show that it is as
      efficient as supervised learning in classification tasks. AGREL is biologically
      realistic and integrates the role of feedback connections, attention effects,
      synaptic plasticity, and reinforcement learning signals into a coherent
      framework.

PMID- 16105223
TI  - Computing with continuous attractors: stability and online aspects.
AB  - Two issues concerning the application of continuous attractors in neural systems
      are investigated: the computational robustness of continuous attractors with
      respect to input noises and the implementation of Bayesian online decoding. In a
      perfect mathematical model for continuous attractors, decoding results for
      stimuli are highly sensitive to input noises, and this sensitivity is the
      inevitable consequence of the system's neutral stability. To overcome this
      shortcoming, we modify the conventional network model by including extra
      dynamical interactions between neurons. These interactions vary according to the
      biologically plausible Hebbian learning rule and have the computational role of
      memorizing and propagating stimulus information accumulated with time. As a
      result, the new network model responds to the history of external inputs over a
      period of time, and hence becomes insensitive to short-term fluctuations. Also,
      since dynamical interactions provide a mechanism to convey the prior knowledge of
      stimulus, that is, the information of the stimulus presented previously, the
      network effectively implements online Bayesian inference. This study also reveals
      some interesting behavior in neural population coding, such as the trade-off
      between decoding stability and the speed of tracking time-varying stimuli, and
      the relationship between neural tuning width and the tracking speed.

PMID- 16105224
TI  - Optimal signal estimation in neuronal models.
AB  - We study optimal estimation of a signal in parametric neuronal models on the
      basis of interspike interval data. Fisher information is the inverse asymptotic
      variance of the best estimator. Its dependence on the parameter value indicates
      accuracy of estimation. Our models assume that the input signal is estimated from
      neuronal output interspike interval data where the frequency transfer function is
      sigmoidal. If the coefficient of variation of the interspike interval is constant
      with respect to the signal, the Fisher information is unimodal, and its maximum
      for the most estimable signal can be found. We obtain a general result and
      compare the signal producing maximal Fisher information with the inflection point
      of the sigmoidal transfer function in several basic neuronal models.

PMID- 16105225
TI  - Finite state automata resulting from temporal information maximization and a
      temporal learning rule.
AB  - We extend Linkser's Infomax principle for feedforward neural networks to a
      measure for stochastic interdependence that captures spatial and temporal signal
      properties in recurrent systems. This measure, stochastic interaction, quantifies
      the Kullback-Leibler divergence of a Markov chain from a product of split chains
      for the single unit processes. For unconstrained Markov chains, the maximization
      of stochastic interaction, also called Temporal Infomax, has been previously
      shown to result in almost deterministic dynamics. This letter considers Temporal
      Infomax on constrained Markov chains, where some of the units are clamped to
      prescribed stochastic processes providing input to the system. Temporal Infomax
      in that case leads to finite state automata, either completely deterministic or
      weakly nondeterministic. Transitions between internal states of these systems are
      almost perfectly predictable given the complete current state and the input, but
      the activity of each single unit alone is virtually random. The results are
      demonstrated by means of computer simulations and confirmed analytically. It is
      furthermore shown numerically that Temporal Infomax leads to a high information
      flow from the input to internal units and that a simple temporal learning rule
      can approximately achieve the optimization of temporal interaction. We relate
      these results to experimental data concerning the correlation dynamics and
      functional connectivities observed in multiple electrode recordings.

PMID- 16105226
TI  - Fast access to concepts in concept lattices via bidirectional associative
      memories.
AB  - Bidirectional associative memories (BAMs) are shown to be capable of precisely
      learning concept lattice structures by Radim Belohlavek. The focus of this letter
      is to show that the BAM, when set up with a concept lattice by setting up
      connection weights according to the rule proposed by Belohlavek, always returns
      the most specific or most generic concept containing the given set of objects or
      attributes when a set of objects or attributes is presented as input to the
      object or attribute layer. A proof of this property is given here, together with
      an example, and a brief application of the property is provided.

PMID- 16105228
TI  - Spasmolytic and antidiarrhoeal properties of the Yucatec Mayan medicinal plant
      Casimiroa tetrameria.
AB  - The Maya of the Yucatan peninsula commonly use the leaves of Casimiroa tetrameria
      for treating gastrointestinal disorders, notably diarrhoea and dysentery, as well
      as gastrointestinal cramps. The phytochemical investigation resulted in the
      isolation of 13 compounds: eight polymethoxylated flavonoids (two as minor
      components with a main constituent), four flavonoid glycosides and one
      furanocoumarin. In this study we used two well-established models in order to
      assess the gastrointestinal effects of C. tetrameria extracts and isolated
      compounds: the USSING-chamber, a pharmacological model for diarrhoea, and the
      isolated guinea pig ileum, a model for modulatory effects on ileum contraction.
      Extracts and the class of polymethoxylated flavonoids showed strong inhibitory
      effects in both models, which provides ex-vivo evidence for the use of this
      botanical drug in the treatment of several gastrointestinal problems, most
      notably diarrhoea. The crude extract, polymethoxylated flavonoid-rich fractions
      and the polymethoxylated flavonoids tested showed prominent antisecretory
      activity. Polymethoxylated flavonoid-rich fractions also inhibited the histamine
      induced contractions in the guinea pig model. The effects are not due to a single
      compound, but to a large number of structurally related compounds that all
      contribute to the effect.

PMID- 16105229
TI  - Cytotoxic activity and effect on nitric oxide production of tirucallane-type
      triterpenes.
AB  - Hexane extract from the bark of Amphipterygium adstringens, as well as its
      principal constituents, masticadienonic acid and 3alpha-hydroxymasticadienolic
      acid, inhibited the growth of five human cancer cell lines. Derivatives of,
      namely 24,25 S-dihydromasticadienonic acid and masticadienolic acid, were also
      evaluated. The results showed that both and had greater activity than on colon
      cancer cell lines. The effects of on the production of nitric oxide (NO) from
      both resting and lipopolysaccharide-activated macrophages were determined. It was
      found that and caused an increase in NO release from resting macrophages; in
      lipopolysaccharide-activated macrophages, only and caused an increase in NO
      production.

PMID- 16105230
TI  - Effect of Larrea tridentata (creosote bush) on cholesterol gallstones and bile
      secretion in hamsters.
AB  - Larrea tridentata (Sesse and Moc. ex DC.) Coville is used for the treatment of
      gallstones in traditional Mexican medicine. The possible prevention or
      elimination of gallstones by ethanolic and aqueous extracts of the leaves and
      twigs of L. tridentata was tested in hamsters fed a rich carbohydrate, fat-free
      diet. In addition, the effects of the ethanolic extract and its main metabolite,
      nordihydroguaiaretic acid, on bile secretion in the perfused liver were tested.
      In the experiment on prevention of gallstones, the dry ethanolic extract at a
      level of 0.5% of diet completely inhibited gallstone formation, lowered biliary
      moles percent cholesterol and increased the proportion of chenodeoxycholic acid
      of hepatic bile. The dry aqueous extract at a level of 1% of diet did not affect
      gallstone frequency or biliary parameters. In the experiment on elimination of
      gallstones, the ethanolic extract significantly reduced gallstone frequency,
      gallbladder bile cholesterol concentration and moles percent cholesterol. Both
      the ethanolic extract and nordihydroguaiaretic acid had cholestatic effects in
      the perfused liver, with an EC50 of 34 and 28 mg dL-1, respectively, when
      perfused for 10 min. This effect was reversible with concentrations up to 40 mg
      dL-1. The results indicate that L. tridentata could be useful in the treatment of
      gallstone disease, however care must be taken due to its hepatotoxicity.

PMID- 16105231
TI  - Antitumour activity of 3-chlorodeoxylapachol, a naphthoquinone from Avicennia
      germinans collected from an experimental plot in southern Florida.
AB  - As part of an ongoing collaborative effort to discover new anticancer agents from
      plants, an extract obtained from the leaves and twigs of Avicennia germinans,
      collected in a coastal area of southern Florida, was identified as possessing
      cytotoxic activity in a panel of human cancer cell lines. Fractionation of the
      petroleum ether partition, using cytotoxicity to guide the fractionation, led to
      the isolation of 3-chlorodeoxylapachol. The antitumour potential of 3
      chlorodeoxylapachol was demonstrated with the in-vivo hollow fibre assay, a model
      of antitumour activity using human cancer cell-filled fibres implanted into mice.
      The possibility that this compound is an artefact of the isolation procedure was
      ruled out by liquid chromatography-mass spectrometry analysis of extracts
      prepared without the use of chlorinated solvent. In conclusion, 3
      chlordeoxylapachol, a secondary metabolite obtained from the chloroform-soluble
      extract of a mangrove tree, was cytotoxic in a panel of human cancer cells, and
      active against KB human cancer cells in the murine hollow fibre antitumour model,
      with selectivity in KB cells for the intravenous site at lower doses, indicating
      possible metabolic activation.

PMID- 16105232
TI  - Anti-HIV activity of dibenzylbutyrolactone-type lignans from Phenax species
      endemic in Costa Rica.
AB  - Previously, we isolated two new dibenzylbutyrolactone-type lignans, named
      phenaxolactones and, from the leaves of Phenax angustifolius Wedd. (Urticaceae).
      In this investigation three new dibenzylbutyrolactone lignans (phenaxolactones),
      together with phenaxolactone, and flavones vitexin, isovitexin, were isolated
      from Phenax rugosus Wedd. leaves collected in Santa Ana, Costa Rica. The
      structures were elucidated using 1D and 2D NMR spectroscopy as well as mass
      spectrometry. Phenaxolactones and flavones and were evaluated for their
      inhibitory activity against HIV-1MN in infected C8166 cells. The most promising
      compound was phenaxolactone with an EC50 value of 3.0 microM, no cytotoxicity at
      112 microM and a therapeutic index value of 37.3.

PMID- 16105233
TI  - Antimycobacterial agents from selected Mexican medicinal plants.
AB  - As part of the ICBG program Bioactive Agents from Dryland Biodiversity of Latin
      America, the present investigation was undertaken to explore the possible
      antimycobacterial potential of compounds derived from selected Mexican medicinal
      plants. Bioassay-guided fractionation of the crude extracts of Rumex
      hymenosepalus (Polygonaceae), Larrea divaricata (Zygophyllaceae), Phoradendron
      robinsonii (Loranthaceae) and Amphipteryngium adstringens (Julianiaceae) led to
      the isolation of several antimycobacterial compounds. Four stilbenoids, two
      flavan-3-ols and three anthraquinones were isolated from R. hymenosepalus. Two
      flavonols and nordihydroguaiaretic acid were obtained from L. divaricata.
      Sakuranetin was the antimycobacterial agent isolated from P. robinsonii. Two
      known triterpenoids and the novel natural product 3-dodecyl-1,8-dihydroxy-2
      naphthoic acid were obtained from A. adstringens. In general, the isolates were
      identified by spectral means. The antimycobacterial activity of the secondary
      compounds isolated from the analysed species, as well as that of nine pure
      compounds previously isolated in our laboratories, was investigated; the MIC
      values ranged from 16 to 128 microg mL-1. Among the tested compounds, the
      glycolipids, sesquiterpenoids and triterpenoids showed the best antimycobacterial
      activity. The antimycobacterial property of the glycolipids is reported for the
      first time. Although the tested compounds showed moderate antimycobacterial
      activity, their presence in the analysed species provides the rationale for their
      traditional use in the treatment of tuberculosis.

PMID- 16105234
TI  - Historical and modern medicinal plant uses--the example of the Ch'orti' Maya and
      Ladinos in Eastern Guatemala.
AB  - Local empirical knowledge about medicinal properties of plants is the basis for
      their use as home remedies. Particularly in developing countries such remedies
      still are an indispensable resource for everyday health care. They form the basis
      for numerous studies on drugs from natural sources. Like other indigenous groups
      across the world, the Ch'orti' Maya in Eastern Guatemala are currently
      experiencing a phase of dramatic cultural change, with their traditional
      knowledge about plants being in great danger of disappearing. During 17 months of
      fieldwork, medicinal plant uses were documented using a semi-quantitative
      approach and analysed using ethnopharmacological methods. The most important
      groups of illnesses treated with plants were gastrointestinal complaints and
      illnesses associated with pain and fever. Field data were compared with mostly
      unpublished historical data collected in the 1930s by the anthropologist Charles
      Wisdom. This comparison showed that medicinal plant uses that are more consistent
      over time are also shared by a larger number of people. A literature search on
      the most frequently mentioned medicinal plants showed that, even for widely used
      medicinal species, phytochemical and pharmacological data are insufficient for
      fully understanding their therapeutic profile. Whereas a few examples of
      potentially dangerous practices were encountered, the limited amount of
      information available mostly supports local medicinal plant usage.

PMID- 16105235
TI  - In-vitro corneal permeation of cannabinoids and their water-soluble phosphate
      ester prodrugs.
AB  - Topically administered cannabinoids have been shown to reduce intraocular
      pressure by interacting with the ocular cannabinoid receptor. Most cannabinoids
      have very poor aqueous solubility, which limits their pharmaceutical development
      and usefulness. In this study, permeation of three cannabinoids
      (arachidonylethanolamide, R-methanandamide and noladin ether) and their water
      soluble phosphate ester prodrugs across isolated rabbit cornea was investigated
      in vitro. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was used to solubilize the
      parent cannabinoids in permeation studies to achieve the required concentration
      in donor and receiving cells. Highest fluxes were obtained with lipophilic parent
      compounds administered with HP-beta-CD, and the fluxes of phosphate esters were
      45-70% that of their corresponding parent compounds. Phosphate esters hydrolysed
      on the surface of the cornea or during the permeation to release the lipophilic
      parent compound, which further permeated the cornea. No phosphate esters were
      detected on the endothelial side of the cornea. Although the phosphate esters had
      lower fluxes than their corresponding parent compounds in these HP-beta-CD
      formulations, the results are promising and the fluxes of phosphate esters are
      significantly higher than the fluxes of parent compounds administered as a
      suspension (due to their low aqueous solubility) without HP-beta-CD.

PMID- 16105236
TI  - Brain permeability of inhaled corticosteroids.
AB  - The aim of this study was to evaluate if the permeability of inhaled
      corticosteroids entering the brain is reduced and if P-glycoprotein (P-gp)
      transporters are involved. Currently employed inhaled corticosteroids were given
      intravenously and intratracheally to rats at a dose of 100 microg kg-1. An ex
      vivo receptor binding assay was used to monitor over 12 h the glucocorticoid
      receptor occupancy in the brain and a systemic reference organ (kidney). The
      involvement of P-gp in the brain permeability of triamcinolone acetonide was
      assessed in wild-type mice and mdr1a(-/-) knockout mice (mice lacking the gene
      for expressing P-gp). After both forms of administration, the average brain
      receptor occupancies were 20-56% of those of the reference organ, with the more
      lipophilic drugs showing a more pronounced receptor occupation. While the
      receptor occupancies in the liver of wild-type and mdr1a(-/-) mice were similar
      after administration of triamcinolone acetonide, brain receptor occupancies in
      mdr1a(-/-) mice were significantly greater (mdr1a(-/-): 47.6%, 40.2-55.0%, n=14;
      2; wild-type: 11.5+/-33.0%, n=14; 3). Penetration into the brain for inhaled
      corticosteroids (especially those of lower lipophilicity) is reduced. Experiments
      in mdr1a(-/-) mice confirmed the involvement of P-gp transporters. Further
      studies are needed to assess whether potential drug interactions at the
      transporter level are of pharmacological significance.

PMID- 16105237
TI  - Effect of charge and lipid concentration on in-vivo percutaneous absorption of
      methyl nicotinate from liposomal vesicles.
AB  - We have investigated the influence of charge and lipid concentration on the in
      vivo percutaneous absorption of a model compound, methyl nicotinate (MN), from
      liposomal vesicles. MN-loaded liposomes were produced by the reverse-phase
      evaporation method (REV) using different concentrations of phosphatidyl choline
      (PC), in association with surfactants such as dioctadecyl dimethyl ammonium
      bromide (DDAB18) and dicetyl phosphate (DCP), which impart a positive or negative
      charge to the systems, respectively. The liposomal suspensions were then
      processed to hydrogels and used to study in-vivo the MN permeation profile. MN
      was chosen as the model compound since it was capable of causing cutaneous
      erythema, the intensity and duration of which was proportional to the amount
      entering the living epidermis over time. The extent of the erythema was monitored
      by reflectance spectrophotometry, a non-invasive technique. In-vivo findings
      showed an interesting MN delayed release, which was proportional to the amount of
      phospholipids in each liposomal formulation. Furthermore, it could be noted that
      the erythematous effect was more prolonged when MN was delivered from neutral or
      negatively-charged liposomal forms.

PMID- 16105238
TI  - Mannosylated niosomes as carrier adjuvant system for topical immunization.
AB  - The aim of this study was to develop mannosylated niosomes as a topical vaccine
      delivery carrier and adjuvant for the induction of both humoral and cellular
      immunity. Bovine serum albumin (BSA)-loaded niosomes composed of sorbitan
      monostearate/sorbitan trioleate (Span 60/Span 85), cholesterol and stearylamine
      as constitutive lipids were prepared by the reverse-phase evaporation method. The
      niosomes were coated with a modified polysaccharide O-palmitoyl mannan (OPM) to
      target them to Langerhan's cells, the major antigen presenting cells found in
      abundance beneath the stratum corneum. Prepared niosomes were characterized in
      vitro for their size, shape, entrapment efficiency and ligand binding
      specificity. The immune stimulating activity was studied by measuring serum IgG
      titre and its subclasses (IgG2a/IgG1 ratio) following topical application of
      various niosomal formulations in albino rats. The results were compared with alum
      adsorbed BSA following topical application and intramuscular injection. It was
      observed that niosomal formulations elicited a significantly higher serum IgG
      titre upon topical application as compared with topically applied alum adsorbed
      BSA (P<0.05). The serum IgG levels were significantly higher for the mannosylated
      niosomes as compared with plain uncoated niosomes (P<0.05). All formulations
      displayed a combined serum IgG2a/IgG1 response, which suggested that the
      formulations were capable of eliciting both humoral and cellular responses. The
      study signified the potential of OPM-coated niosomes as a topical vaccine
      delivery carrier and adjuvant. The proposed system would be simple, stable, and
      cost effective and might be clinically acceptable.

PMID- 16105239
TI  - Role of monocarboxylic acid transporters in the cellular uptake of NSAIDs.
AB  - The present study investigated the cellular uptake mechanism of non-steroidal
      anti-inflammatory drugs (NSAIDs) in Caco-2 cells. Diflunisal, diclofenac,
      ketoprofen and naproxen exhibited a strong inhibition effect on the cellular
      uptake of [14C]-benzoic acid in Caco-2 cells with IC50 values of 0.05-0.44 mM.
      The inhibition of naproxen and ketoprofen against the membrane transport of [14C]
      benzoic acid appeared to be competitive, with Ki values of 0.22 and 0.38 mM,
      respectively. The membrane permeability of naproxen and ketoprofen was
      concentration dependent, implying that the cellular uptake pathway of ketoprofen
      and naproxen was saturable at the higher concentration. Furthermore, the cellular
      accumulation of ketoprofen was significantly reduced in the presence of benzoic
      acid and L-lactic acid, two known substrates of monocarboxylic acid transporter 1
      (MCT1). These results suggest that MCT1 contributes at least in part to the
      carrier-mediated transport of NSAIDs containing a carboxylic acid moiety across
      the apical membrane in Caco-2 cells.

PMID- 16105240
TI  - Effects of 4-piperidinomethyl-2-isopropyl-5-methylphenol on oxidative stress and
      calcium current.
AB  - 4-Piperidinomethyl-2-isopropyl-5-methylphenol (THPI) was synthesized by reaction
      of thymol with piperidine and formaldehyde. The biological effect of THPI on
      superoxide anion scavenging activity, antiplatelet activity and calcium current
      inhibition were investigated. THPI (50 microM) was shown to be a scavenger of
      superoxide radicals in human neutrophils stimulated with N-formyl-Met-Leu-Phe
      (66% inhibition). Since superoxide anions are essential for platelet aggregation
      and L-type Ca2+-channel activity, we further found that THPI inhibited platelet
      aggregation induced by arachidonic acid (IC50 46.80+/-6.88 microM). The effect of
      THPI on Ca2+ current in NG108-15 cells was investigated using the whole-cell
      voltage-clamp technique. THPI inhibited voltage-dependent L-type Ca2+ current
      (ICa, L). The IC50 value of THPI-induced inhibition of ICa, L was 3.60+/-0.81
      microM. THPI caused no change in the overall shape of the current-voltage
      relationship of ICa, L. This indicates that THPI is an inhibitor of ICa, L in
      NG108-15 cells. Therefore, the channel-blocking properties of THPI may contribute
      to the underlying mechanism by which it affects neuronal or neuroendocrine
      function. Furthermore, no significant cytotoxic effects of THPI (0.3-50 microM)
      were observed in NG108-15 cells. The results indicate that THPI is a potential
      reactive oxygen species scavenger and may prevent platelet aggregation or inhibit
      L-type Ca2+-channel activity, possibly by scavenging reactive oxygen species.

PMID- 16105241
TI  - Pluchea lanceolata attenuates cadmium chloride induced oxidative stress and
      genotoxicity in Swiss albino mice.
AB  - Cadmium intoxication induces lipid peroxidation and causes oxidative damage to
      various tissues by altering antioxidant defence system enzymes. At 24 h after
      treatment with a single intraperitoneal dose of cadmium chloride (5 mg kg-1),
      Swiss albino mice showed a significant increase in the levels of malanodialdehyde
      and xanthine oxidase (P<0.001), and a concomitant depletion of renal glutathione,
      catalase (P<0.001) and other antioxidant enzymes. CdCl2 also led to a
      simultaneous increase in micronuclei formation (P<0.001) and chromosomal
      aberrations (P<0.05) in mouse bone marrow cells. Oral pre-treatment with Pluchea
      lanceolata extract at doses of 100 and 200 mg kg-1 for 7 consecutive days before
      CdCl2 intoxication caused a significant reduction in malanodialdehyde formation
      and xanthine oxidase activity (P<0.001). A significant restoration of the
      activity of antioxidant defence system enzymes such as catalase, glutathione
      peroxidase (P<0.05), glutathione-S-transferase and glutathione reductase
      (P<0.001) was observed. A significant dose-dependent decrease in chromosomal
      aberrations and micronuclei formation was also observed (P<0.05). The results
      indicate that pre-treatment with P. lanceolata attenuates cadmium chloride
      induced oxidative stress and genotoxicity by altering antioxidant enzymes and
      reducing chromatid breaks and micronuclei formation.

PMID- 16105242
TI  - Long-term treatment with Hachimi-jio-gan attenuates kidney damage in
      spontaneously diabetic WBN/Kob rats.
AB  - Diabetes mellitus is now the most common cause of end-stage renal failure. In
      this study, the effects of Hachimi-jio-gan on diabetic kidney damage in
      spontaneously diabetic WBN/Kob rats were examined. Oral administration of Hachimi
      jio-gan to WBN/Kob rats for 25 weeks significantly suppressed urinary protein
      excretion. It did not affect body weight loss or blood glucose levels, whereas it
      reversed the increase in kidney weight of WBN/Kob rats. Hachimi-jio-gan also
      reduced fibronectin and transforming growth factor beta1 (TGF-beta1) protein
      expression in the renal cortex. Furthermore, renal lipid peroxidation levels of
      WBN/Kob rats given Hachimi-jio-gan were significantly lower than those of
      untreated controls. Renal superoxide dismutase activity was elevated by Hachimi
      jio-gan treatment in a dose-dependent manner. These results suggested that
      Hachimi-jio-gan could prevent diabetic kidney damage by reducing renal oxidative
      injury and expression of fibronectin and TGF-beta1 proteins, which are all
      involved in the pathophysiology of diabetic nephropathy.

PMID- 16105243
TI  - Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine
      in-vitro and in tumour-bearing mice.
AB  - The cytotoxic effect of various concentrations of echitamine chloride was studied
      in HeLa, HepG2, HL60, KB and MCF-7 cell lines in-vitro and in mice bearing
      Ehrlich ascites carcinoma (EAC). Exposure of various cells to different
      concentrations of echitamine chloride resulted in a concentration-dependent cell
      killing, and KB cells were found to be most sensitive amongst all the cells
      evaluated. EAC mice treated with 1, 2, 4, 6, 8, 12 or 16 mg kg-1 echitamine
      chloride showed a dose-dependent elevation in the anti-tumour activity, as
      evident by increased number of survivors in comparison with the non-drug treated
      controls. The highest dose of echitamine chloride (16 mg kg-1) caused toxicity in
      the recipient mice, therefore 12 mg kg-1 was considered the best cytotoxic dose
      for its anti-tumour effect. Administration of 12 mg kg-1 echitamine chloride
      resulted in an increase in the median survival time (MST) up to 30.5 days, which
      was 11.5 days higher than the non-drug treated control (19 days). Administration
      of 16 mg kg-1 echitamine chloride to EAC mice resulted in a time dependent
      elevation in lipid peroxidation that reached a peak at 6 h post-treatment,
      whereas glutathione concentration declined in a time dependent manner and a
      maximum decline was reported at 3 h post-treatment. Our study demonstrated that
      echitamine chloride possessed anti-tumour activity in-vitro and in-vivo.

PMID- 16105244
TI  - Centella asiatica accelerates nerve regeneration upon oral administration and
      contains multiple active fractions increasing neurite elongation in-vitro.
AB  - Axonal regeneration is important for functional recovery following nerve damage.
      Centella asiatica Urban herb, also known as Hydrocotyle asiatica L., has been
      used in Ayurvedic medicine for centuries as a nerve tonic. Here, we show that
      Centella asiatica ethanolic extract (100 microg mL-1) elicits a marked increase
      in neurite outgrowth in human SH-SY5Y cells in the presence of nerve growth
      factor (NGF). However, a water extract of Centella was ineffective at 100 microg
      mL-1. Sub-fractions of Centella ethanolic extract, obtained through silica-gel
      chromatography, were tested (100 microg mL-1) for neurite elongation in the
      presence of NGF. Greatest activity was found with a non-polar fraction (GKF4).
      Relatively polar fractions (GKF10 to GKF13) also showed activity, albeit less
      than GKF4. Thus, Centella contains more than one active component. Asiatic acid
      (AA), a triterpenoid compound found in Centella ethanolic extract and GKF4,
      showed marked activity at 1 microM (microg mL-1). AA was not present in GKF10 to
      GKF13, further indicating that other active components must be present. Neurite
      elongation by AA was completely blocked by the extracellular-signal-regulated
      kinase (ERK) pathway inhibitor PD 098059 (10 microM). Male Sprague-Dawley rats
      given Centella ethanolic extract in their drinking water (300-330 mg kg-1 daily)
      demonstrated more rapid functional recovery and increased axonal regeneration
      (larger calibre axons and greater numbers of myelinated axons) compared with
      controls, indicating that the axons grew at a faster rate. Taken together, our
      findings indicate that components in Centella ethanolic extract may be useful for
      accelerating repair of damaged neurons.

PMID- 16105245
TI  - Sound source identification with ANR earmuffs.
AB  - The effect of hearing protective earmuffs which incorporate active noise
      reduction (ANR) on sound source identification was studied. The purpose was
      determine whether ANR interfered with the encoding of cues normally used for
      directional hearing. Right/left, front/back and within quadrant confusions were
      assessed in quiet using a circular array of eight loudspeakers. Three stimuli,
      one-third octave bands centred at 0.5 kHz and 4 kHz and broadband noise, were
      presented. These enabled an assessment of the utilization of mainly interaural
      time-of-arrival and level differences, and binaural and spectral cues in
      combination, respectively. Two groups of normal hearing subjects aged 18-30 and
      40-55 years, half male and half female, participated. Overall, age, gender, and
      ANR were not significant determinants of outcome. The probably of correctly
      discriminating among the eight speakers decreased significantly with the muffs
      worn, relative to unoccluded listening by 10%, 35% and 40% for the 0.5 kHz, 4 kHz
      and broadband stimuli, respectively. The pattern of errors indicated that the
      earmuffs interfered with the encoding of both binaural (interaural level
      differences) and spectral cues. With ANR small additional right/left confusions
      were observed for the low-frequency stimulus (time-of arrival cue) for speakers
      close to the midline axis. The results provide further evidence that earmuffs
      should not be used in situations where the perception of the direction of hazard
      is a concern. ANR technology does not appear to increase the handicap.

PMID- 16105246
TI  - Strength of noise effects on memory as a function of noise source and age.
AB  - The objectives in this paper were to analyse noise effects on episodic and
      semantic memory performance in different age groups, and to see whether age
      interacted with noise in their effects on memory. Data were taken from three
      separate previous experiments, that were performed with the same design,
      procedure and dependent measures with participants from four age groups (13-14,
      18-20, 35-45 and 55-65 years). Participants were randomly assigned to one of
      three conditions: (a) meaningful irrelevant speech, (b) road traffic noise, and
      (c) quiet. The results showed effects of both noise sources on a majority of the
      dependent measures, both when taken alone and aggregated according to the nature
      of the material to be memorised. However, the noise effects for episodic memory
      tasks were stronger than for semantic memory tasks. Further, in the reading
      comprehension task, cued recall and recognition were more impaired by meaningful
      irrelevant speech than by road traffic noise. Contrary to predictions, there was
      no interaction between noise and age group, indicating that the obtained noise
      effects were not related to the capacity to perform the task. The results from
      the three experiments taken together throw more light on the relative effects of
      road traffic noise and meaningful irrelevant speech on memory performance in
      different age groups.

PMID- 16105247
TI  - Noise exposure and subjective hearing symptoms among school children in Sweden.
AB  - OBJECTIVE: The aim of the present study was to evaluate factors of importance for
      the experience of temporary threshold shift (TTS), noise- induced tinnitus (NIT),
      spontaneous tinnitus (ST) in school children. SUBJECTS AND METHODS: A total of
      671 students aged 13-16 years old were asked to fill in a questionnaire
      containing items concerning TTS, NIT, ST, hearing loss (HL), heredity for HL,
      noise exposure, history of otitis media, symptoms of anxiety and depression,
      psychosocial factors and habits, life satisfaction, chronic medical conditions,
      age, gender and height. The questionnaire was filled in during school hours.
      RESULTS: Correlations were found with exercise and eating habits, sleep
      disturbances, BMI, depressive and anxiety disorders, heredity for HL and noise
      exposure dosage. The risk for TTS was nine times higher in students who reported
      having a verified hearing loss than in subjects without subjective or verified
      complaints of hearing loss. The risk for NIT was approximately four times higher
      in the group who visited concerts 6-12 times per year as compared to those who
      never attended concerts. There was almost a threefold increase in the risk for ST
      in the group that sometimes experienced TTS, as compared to those without TTS,
      and a tenfold increase in risk for ST in those who reported having a verified
      hearing loss. CONCLUSION: In school children, exposure to leisure noise is
      correlated with tinnitus and the risk increases with increasing noise exposure.
      Sensitivity to subjective hearing loss has similar risk factors as seen for
      metabolic syndrome and we suggest that this sensitivity may be another side of
      metabolic syndrome.

PMID- 16105248
TI  - Noise annoyance in Canada.
AB  - The present paper provides the results from two nation-wide telephone surveys
      conducted in Canada on a representative sample of 5,232 individuals, 15 years of
      age and older. The goals of this study were to gauge Canadians' annoyance towards
      environmental noise, identify the source of noise that is viewed as most annoying
      and quantify annoyance toward this principal noise source according to
      internationally accepted specifications. The first survey revealed that nearly 8%
      of Canadians in this age group were either very or extremely bothered, disturbed
      or annoyed by noise in general and traffic noise was identified as being the most
      annoying source. A follow-up survey was conducted to further assess Canadians'
      annoyance towards traffic noise using both a five-item verbal scale and a ten
      point numerical scale. It was shown that 6.7% of respondents indicated they were
      either very or extremely annoyed by traffic noise on the verbal scale. On the
      numerical scale, where 10 was equivalent to "extremely annoyed" and 0 was
      equivalent to "not at all annoyed", 5.0% and 9.1% of respondents rated traffic
      noise as 8 and above and 7 and above, respectively. The national margin of error
      for these findings is plus or minus 1.9 percentage points, 19 times out of 20.
      The results are consistent with an approximate value of 7% for the percentage of
      Canadians, in the age group studied, highly annoyed by road traffic noise (i.e.
      about 1.8 million people). We found that age, education level and community size
      had a statistically significant association with noise annoyance ratings in
      general and annoyance specifically attributed to traffic noise. The use of the
      International Organization for Standardization/Technical Specification (ISO/TS)
      15666 questions for assessing noise annoyance makes it possible to compare our
      results to other national surveys that have used the same questions.

PMID- 16105249
TI  - Combined effects of noise and styrene on hearing: comparison between active and
      sedentary rats.
AB  - In this study, two investigations were carried out with adult Long-Evans rats
      exposed to increasing concentrations of styrene. In the first experiment, the
      hearing of rats, which were forced to walk in a special wheel during the
      exposure, was compared to that of rats which were sleepy in their cage. The
      active rats were exposed to styrene concentrations ranging from 300 to 600 ppm,
      whereas the sedentary rats were exposed from 500 to 1000 ppm for 4 weeks, 5 days
      per week, 6 hours per day. In the second experiment, designed to evaluate the
      hearing risks at threshold limit values, active rats were exposed either to a
      noise having a Leq8h of 85 dB (equivalent level of a continuous noise for a
      typical 8-h workday), or to 400-ppm styrene or to a simultaneous exposure to
      noise and styrene. In both experiments, auditory function was tested by auditory
      evoked potentials from the inferior colliculus and completed by morphological
      analyses of the organ of Corti. The results of the first experiment showed that
      the same amount of styrene-induced hearing loss can be obtained by using
      concentrations approximately 200 ppm lower in active rats than in sedentary rats.
      The second investigation showed that, in spite of the low-intensity noise and the
      low-concentration of styrene, there is a clear risk of potentiation of styrene
      induced hearing loss by noise. These findings and exposure conditions were
      discussed and extrapolated with regard to the risk assessment for human beings.
      The authors propose to decrease the French threshold limit value of styrene for
      ensuring a high level of protection for human hearing.

PMID- 16105250
TI  - Ethyl sulfate: a metabolite of ethanol in humans and a potential biomarker of
      acute alcohol intake.
AB  - This study identified ethyl sulfate (EtS) in human urine and compared the
      excretion characteristics of EtS with that of ethanol and ethyl glucuronide
      (EtG). Urine samples were collected from healthy subjects after a single ethanol
      dose, and also selected from routine clinical samples. Simultaneous analysis of
      EtS and EtG was performed by direct electrospray liquid chromatography-mass
      spectrometry in the negative ion mode, with selected-ion monitoring of the
      pseudomolecular ions at m/z 125 for EtS (M(w) 126 g/mol) and m/z 221 for EtG
      (M(w) 222 g/mol). The identity of EtS in authentic urine specimens was
      established by co-chromatography with reference substance, the presence of
      product ions (m/z 97 and 80 from m/z 125) with correct relative intensity, and a
      correct sulfur isotope ratio for (34)S (m/z 127). After healthy subjects drank
      ethanol, EtS showed a much longer, dose-dependent elimination half-life than the
      parent compound. No EtS was detected in urines collected after abstention from
      ethanol for several days prior to sampling. Among 354 consecutive clinical
      samples, 86 were positive for both EtS and EtG with a mean EtG/EtS molar ratio of
      2.3 (median 1.7). Another three urine samples were only positive for EtS and four
      only for EtG. The present results confirm that sulfate conjugation is a normal
      but minor metabolic pathway for ethanol in humans, and EtS a common constituent
      in the urine after alcohol intake. It is also indicated that the concurrent
      determination of EtS and EtG will improve sensitivity, when being used as
      biomarkers of recent drinking.

PMID- 16105251
TI  - Papain: a novel urine adulterant.
AB  - The estimated number of employees in the United Stated screened annually for
      illicit drugs is approximately 20 million, with marijuana being the most
      frequently abused drug. Urine adulterants provide an opportunity for illicit drug
      users to obtain a false-negative result on commonly used primary drug screening
      methods such as the enzyme multiplied immunoassay technique and the fluorescence
      polarized immunoassay technique (FPIA). Typical chemical adulterants such as
      nitrites are easily detected or render the urine specimen invalid as defined in
      the proposed SAMHSA guidelines for specimen validity testing based on creatinine,
      specific gravity, and pH. Papain is a cysteine protease with intrinsic ester
      hydrolysis capability. The primary metabolite of the psychoactive chemical in
      marijuana, 11-norcarboxy-Delta9-tetrahydrocannibinol (THC-COOH), was assayed by
      FPIA in concentrations ranging from 25 to 500 ng/mL, at pH values ranging from
      4.5 to 8, over the course of 3 days with papain concentrations ranging from 0 to
      10 mg/mL. FPIA analysis of other frequently abused drugs: amphetamines,
      barbiturates, benzodiazepines, cocaine, opiates, and phencyclidine, along with
      gas chromatography-mass spectrometry (GC-MS) of THC-COOH and high-pressure liquid
      chromatography-ultraviolet detection (HPLC-UV) of nordiazepam was performed in
      order to determine if the mechanism of urine adulteration by papain was analyte
      specific. Control and adulterated urine specimens (n = 30) were assayed for
      creatinine, specific gravity, and pH to determine if papain rendered the
      specimens invalid based on the proposed SAMHSA guidelines. There was a direct pH,
      temperature, and time-dependent correlate between the increase in papain
      concentration and the decrease in THC-COOH concentration from the untreated
      control groups (p < 0.01). The average 72-h THC-COOH concentration decrease at pH
      6.2 with a papain concentration of 10 mg/mL was 50%. Papain did not significantly
      decrease the concentration of the other drugs analyzed with the exception of
      nordiazepam. GC-MS of THC-COOH and HPLC-UV of nordiazepam revealed a 66% and 24%
      decrease in concentration of the respective analyte with 10 mg/mL papain after 24
      h at room temperature (approximately 23 degrees C). No adulterated specimens were
      rendered invalid based on the SAMHSA guidelines. Immediate FPIA analysis is
      suggested to minimize the interfering effects of papain with regards to primary
      drug screening.

PMID- 16105252
TI  - MDMA and MDA concentrations in antemortem and postmortem specimens in fatalities
      following hospital admission.
AB  - Over the last 15 years, numerous deaths involving "Ecstasy" (3,4
      methylenedioxymethamphetamine, MDMA) have been reported and described in the
      literature. In most cases, either antemortem or postmortem concentration data are
      available. Because of the wide range of results and potential idiosyncratic
      nature of MDMA toxicity, interpretation of both antemortem and postmortem
      concentrations is difficult. The possible influence of postmortem redistribution
      may be an overlooked factor, but existing data involve postmortem concentrations
      from varying anatomical sites. However, this paper describes for the first time
      an evaluation of the concentrations of MDMA and 3,4-methylenedioxyamphetamine
      (MDA) found in five fatalities admitted to hospital where both antemortem and
      postmortem blood samples were available. Admission MDMA and MDA concentrations
      ranged between 0.55 and 4.33 mg/L and 0 and 0.10 mg/L, respectively, in
      antemortem serum/plasma. Postmortem blood MDMA and MDA concentrations ranged
      between 0.47 and 28.39 mg/L and 0.02 and 1.33 mg/L, respectively. Postmortem
      concentrations were higher than corresponding antemortem concentrations in all 5
      cases with postmortem/antemortem ratios between 1.1 and 6.6 for MDMA and 1.5 and
      13.3 for MDA. Differences in concentrations were also observed between anatomical
      sites, with central sites (e.g., heart) having much higher concentrations than
      peripheral sites (e.g., femoral). Overall, MDMA and MDA appear to exhibit
      postmortem redistribution and concentrations measured in postmortem specimens
      (even from peripheral sites) are not directly comparable with antemortem findings
      close to or prior to death.

PMID- 16105253
TI  - GC-MS quantitation of codeine, morphine, 6-acetylmorphine, hydrocodone,
      hydromorphone, oxycodone, and oxymorphone in blood.
AB  - A method is described for the simultaneous analysis of seven opiates, codeine,
      morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone, and
      oxymorphone, in blood samples by gas chromatography-mass spectrometry (GC-MS).
      One milliliter of blood is combined with an internal standard mixture containing
      200 ng of each of the seven deuterated opiates. Two milliliters of acetonitrile
      is added to precipitate the proteins and cellular material. After centrifugation,
      the clear supernatant is removed, and the acetonitrile is evaporated. The
      remaining aqueous portion is adjusted to pH 9 with sodium bicarbonate buffer, and
      the drugs are extracted into chloroform/ trifluoroethanol (10:1). The organic
      extractant is transferred and dried under nitrogen. The residue is reconstituted
      in dilute hydrochloric acid and washed consecutively with hexane and chloroform.
      The purified aqueous portion is adjusted to pH 9 with bicarbonate buffer, and the
      drugs are again extracted into chloroform/trifluoroethanol (10:1). The organic
      portion is removed from the aqueous fraction and dried under nitrogen. The
      residue is consecutively derivatized with methoxyamine and propionic anhydride
      using pyridine as a catalyst. The ketone groups on hydrocodone, hydromorphone,
      oxycodone, and oxymorphone are converted to methoximes. Hydroxyl groups present
      at the O(3) and O(6) positions of codeine, morphine, 6-acetylmorphine,
      hydromorphone, and oxymorphone are converted to their respective propionyl
      esters. After a post-derivatization purification step, the extracts are analyzed
      by full scan GC-MS using electron impact ionization. The method is linear to at
      least 2000 ng/mL. Day-to-day precision (N = 15) at 500 ng/mL and 75 ng/mL were
      less than 10% for all seven targeted opiates. Extraction efficiencies at these
      two concentrations ranged from 50% to 68%. For each opiate, the limit of
      quantitation was 10 ng/mL, and the limit of detection was 2 ng/mL.

PMID- 16105254
TI  - Determination of furosemide in whole blood using SPE and GC-EI-MS.
AB  - A simple and rapid method was validated to determine furosemide in whole blood.
      The experimental work was performed so that all validation parameters are
      considered simultaneously in a one-day assay protocol. A solid-phase extraction
      procedure using BondElut-LRC Certify columns was used to extract this compound
      from blood samples, while ketoprofen was used as an internal standard. The
      extracts were analyzed by gas chromatography-electron ionization-mass
      spectrometry after on-column derivatization with trimethylanilinium hydroxide
      (0.2M in methanol). Calibration curves were prepared daily, between 0.10 and 5.00
      microg/mL, and the correlation coefficients were above 0.9910. The calculated
      limits of detection and quantitation were 0.010 and 0.045 microg/mL,
      respectively. Control samples at low, medium, and high concentrations (0.30,
      0.75, and 3.00 microg/mL) of furosemide of an independent source were measured in
      the same day. Precision and trueness, calculated in terms of relative standard
      deviation (%), were less than 15% for all concentration levels. The relative
      recoveries calculated for the three levels of the control samples were 104%, 89%,
      and 91%, respectively. In general, a sensitive, specific, and reliable procedure
      has been developed for the determination of furosemide in whole blood samples and
      was found suitable for the application in postmortem forensic toxicology routine
      analysis.

PMID- 16105255
TI  - Evaluation of ketamine abuse using hair analysis: concentration trends in a
      Singapore population.
AB  - This paper presents a method for the detection of ketamine in hair. Hair samples
      (25 mg) were washed, pulverized, and digested in hydrochloric acid (0.5 M)
      overnight at 45 degrees C. The samples were extracted by an automated solid-phase
      extraction procedure, and the extracts were subsequently analyzed using gas
      chromatography-mass spectrometry in selected ion monitoring mode. Linearity up to
      120 ng/mg was obtained for both ketamine and norketamine with correlation
      coefficients of 0.9987 and 0.9985, respectively. Limit of detection was found to
      be at 0.4 ng/mg for both drugs while the limit of quantitation was found to be
      0.6 and 0.8 ng/mg for ketamine and norketamine, respectively. The validated
      method was used in the analysis of 91 hair segments obtained from 54 ketamine
      abusers. Based upon the voluntary confession of the ketamine abusers, a
      correlation between the amount of ketamine detected and the frequency of abuse
      was observed.

PMID- 16105256
TI  - Hair analysis for cocaine: the requirement for effective wash procedures and
      effects of drug concentration and hair porosity in contamination and
      decontamination.
AB  - It has been proposed that issues of external contamination of hair can be
      resolved by the presence of metabolites. This is true for some drugs in some
      circumstances. However, even if some metabolites such as cocaethylene are
      sufficiently definitive to indicate certainty of use, others such as
      benzoylecgonine can occur as contaminants. In addition, for phencyclidine, only
      the parent compound is determined. Therefore, effective washing procedures are
      needed to rule out contamination as the source of the parent or metabolite. The
      protection provided by cutoffs is also dependent on washing to remove surface
      contamination, which can range from very little to greater than 20 times the
      amount in the hair. In cocaine-positive head hair samples from 67 subjects with
      cocaine-positive urine tests, contamination of positive hair samples ranged from
      0.7 to 8009 ng/10 mg hair, demonstrating that analyses of such samples to
      determine use is meaningless without removal of contamination. Wash procedures
      have been a focus of this laboratory for many years. In this paper, the
      effectiveness of our wash procedure was further challenged by application to
      negative hair (blonde, auburn, brown, and black) contaminated by soaking for 1 h
      in 1000, 10,000, and 50,000 ng cocaine/mL water. The uptake of the cocaine was
      approximately linear with increasing concentrations of cocaine in the soaking
      solutions. By application of the wash criterion, all samples were clearly
      identified as contaminated (i.e., negative). The effects of hair porosity on
      uptake of cocaine were also studied with 10 hair samples of all colors. Permed
      and unpermed samples were soaked in 10,000 ng cocaine/mL for 1 hour. All hair
      responded to the perm with increased uptake, and all were decontaminated or
      identified as contaminated (i.e., negative for cocaine use). Porosity, not hair
      color, determined the rate of penetration of hair by cocaine in solution, and,
      likewise, washing characteristics were unrelated to hair color.

PMID- 16105257
TI  - Assessment of driving capability through the use of clinical and psychomotor
      tests in relation to blood cannabinoids levels following oral administration of
      20 mg dronabinol or of a cannabis decoction made with 20 or 60 mg Delta9-THC.
AB  - Delta(9)-Tetrahydrocannabinol (THC) is frequently found in the blood of drivers
      suspected of driving under the influence of cannabis or involved in traffic
      crashes. The present study used a double-blind crossover design to compare the
      effects of medium (16.5 mg THC) and high doses (45.7 mg THC) of hemp milk
      decoctions or of a medium dose of dronabinol (20 mg synthetic THC, Marinol on
      several skills required for safe driving. Forensic interpretation of cannabinoids
      blood concentrations were attempted using the models proposed by Daldrup
      (cannabis influencing factor or CIF) and Huestis and coworkers. First, the time
      concentration-profiles of THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH
      THC) (active metabolite of THC), and 11-nor-9-carboxy-Delta(9)
      tetrahydrocannabinol (THCCOOH) in whole blood were determined by gas
      chromatography-mass spectrometry-negative ion chemical ionization. Compared to
      smoking studies, relatively low concentrations were measured in blood. The
      highest mean THC concentration (8.4 ng/mL) was achieved 1 h after ingestion of
      the strongest decoction. Mean maximum 11-OH-THC level (12.3 ng/mL) slightly
      exceeded that of THC. THCCOOH reached its highest mean concentration (66.2 ng/mL)
      2.5-5.5 h after intake. Individual blood levels showed considerable intersubject
      variability. The willingness to drive was influenced by the importance of the
      requested task. Under significant cannabinoids influence, the participants
      refused to drive when they were asked whether they would agree to accomplish
      several unimportant tasks, (e.g., driving a friend to a party). Most of the
      participants reported a significant feeling of intoxication and did not
      appreciate the effects, notably those felt after drinking the strongest
      decoction. Road sign and tracking testing revealed obvious and statistically
      significant differences between placebo and treatments. A marked impairment was
      detected after ingestion of the strongest decoction. A CIF value, which relies on
      the molar ratio of main active to inactive cannabinoids, greater than 10 was
      found to correlate with a strong feeling of intoxication. It also matched with a
      significant decrease in the willingness to drive, and it matched also with a
      significant impairment in tracking performances. The mathematic model II proposed
      by Huestis et al. (1992) provided at best a rough estimate of the time of oral
      administration with 27% of actual values being out of range of the 95% confidence
      interval. The sum of THC and 11-OH-THC blood concentrations provided a better
      estimate of impairment than THC alone. This controlled clinical study points out
      the negative influence on fitness to drive after medium or high dose oral THC or
      dronabinol.

PMID- 16105258
TI  - Amphetamine binding to synthetic melanin and scatchard analysis of binding data.
AB  - Previous research into drug-hair binding shows that hair color affects drug-hair
      binding. There are no structural disparities in hair of different colors other
      than the type and content of melanin present. For this reason, this investigation
      focuses on synthetic eumelanin as a site for drug interaction using amphetamine
      as the candidate drug. The binding study was carried out at room temperature. The
      interaction between synthetic eumelanin and amphetamine was monitored using UV
      Vis spectrophotometry at 257.2 nm. As the molecular weight of melanin is unknown,
      the number of binding sites could not be calculated directly. Hence the ratio of
      the number of mumoles of drug bound and the dry weight of melanin in mug was
      considered. Equilibrium was reached when approximately 32% of the drug was bound
      to melanin. Hence this study proves that amphetamine binds to synthetic eumelanin
      in vitro. Data interpretation using Scatchard analysis yielded a curvilinear plot
      with upward concavity indicating multiple binding sites on melanin and negative
      cooperativity.

PMID- 16105259
TI  - Opiate concentrations in hair from subjects in a controlled heroin-maintenance
      program and from opiate-associated fatalities.
AB  - One month before (T-1) and 12 months after (T12) controlled intravenous
      administration of pharmaceutical heroin-HCl (10-1000 mg/d) in the context of a
      heroin-maintenance program, concentrations of opiates in head hair were
      determined (n = 46), using a validated gas chromatography-mass spectrometry
      method with limits of detection (LOD) between 0.02 and 0.04 ng/mg. In addition, a
      collective of opiate-associated fatalities was examined (n = 24). The obtained
      concentrations in the proximal segment (1 cm) of the patients were between 0.04
      and 1.16 ng/mg (mean 0.13 ng/mg) for heroin (HER), between 0.02 and 32.41 ng/mg
      (mean 1.48 ng/mg) for 6-monoacetylmorphine (MAM) and between 0.03 and 11.79 ng/mg
      (mean 1.19 ng/mg) for morphine (MOR). With the exception of the analyte HER,
      there was no other statistically significant difference in the concentrations in
      comparison to the opiate fatalities [HER 1.55-5.20 ng/mg mean 3.38 ng/mg), MAM
      0.04-30.01 ng/mg (mean 2.14 ng/mg), and MOR 0.03-11.87 ng/mg (mean 1.15 ng/mg) in
      the proximal segments]. After controlled HER administration, a correlation
      between the dose and the total opiate concentration in the hair was found (r =
      0.66). These results disagree with the observations of authors who found only
      limited dose-concentration relationships after heroin abuse in hair. When
      considering a single analyte, the coefficient of correlation increased in
      correspondence to the respective plasma half-life (r = 0.42, r = 0.58, and r =
      0.69 for HER, MAM, and MOR). The latter findings are in agreement with the report
      that states that this correlation is influenced by the plasma half-lifes of
      analytes. Codeine and acetylcodeine (AC) were detected in 50% and 43.5% (T-1) and
      13% and 10.9% (T12) of the samples of the HER-maintenance program, as well as in
      33.3% and 16.7% in opiate-associated fatalities, respectively. The lack of
      differences between obtained opiate concentrations in the hair of participants in
      a controlled heroin maintenance program and of opiate-associated fatalities does
      not support the hypothesis that an absence of tolerance can be regarded as a
      potential cause of death. In addition, the lack of AC, which was also observed in
      the majority of the deaths, questions its applicability as a characteristic
      marker of the consumption of illicit heroin.

PMID- 16105260
TI  - The identification of a chlorinated MDMA.
AB  - The abuse of the designer amphetamines such as 3,4-methylenedioxymethamphetamine
      (MDMA) is increasing throughout the world. They have become popular drugs at all
      night techno dance parties, and their detection is an important issue. The
      objective of the presented study was to identify an unknown compound detected by
      thin-layer chromatography (TLC) in the urine of an illicit drug abuser. The
      compound was isolated by TLC and analyzed by gas chromatography-mass spectrometry
      (GC-MS) in electron ionization (EI) and positive ion chemical ionization (PICI)
      mode to elucidate its chemical structure. Based on EI-MS and PICI-MS mass
      spectral data, the unknown compound was indicated to be a structure similar to
      MDMA, substituted by a single chlorine atom-a chlorinated MDMA (Cl-MDMA). To
      confirm the Cl-MDMA structure, the unknown compound was silylated,
      trifluoroacetylated, acetylated, heptafluorobutyrylated, and analyzed by GC-MS.
      The position of the chlorine atom cannot be assigned exactly from the mass
      spectral data presented here; however, we believe that the unknown compound could
      be 6-Cl-MDMA.

PMID- 16105261
TI  - Comparison of the sensitivity and specificity of six immunoassays for the
      detection of amphetamines in urine.
AB  - We analyzed 225 urine samples with FPIA (Abbott Amphetamine/Methamphetamine II on
      ADx and AxSYM), EMIT (Emit II Plus Monoclonal Amphetamine/Metamphetamine assay
      and EMIT II Plus Amphetamines assay, EMIT N), and KIMS (standard protocol and
      MDMA protocol, KIMS and KIMS X, respectively) immunoassays and compared their
      sensitivity and specificity. All assays were calibrated and used semi
      quantitatively. All samples that screened positive by any amphetamine screening
      method and 15% of the negative samples were confirmed by liquid chromatography
      tandem mass spectrometry (LC-MS-MS). A sample was considered positive for
      amphetamines if amphetamine, methamphetamine, methylenedioxymethamphetamine,
      methylenedio-xyethylamphetamine, or methylenedioxyamphetamine was present at 250
      ng/mL. Ninety (40%) of the samples were positive by LC-MS-MS. The areas under the
      receiver operating characteristic curve varied between 0.972 (KIMS X) and 1.000
      (ADx). The optimal cut-off concentrations varied between 271 ng/mL (EMIT N) and
      723 ng/mL (AxSYM). The sensitivity was 100% for ADx and between 93 and 95% for
      the other assays. The specificity varied between 88% (KIMS) and 100% (EMIT N).
      Use of a 500 ng/mL screening cut-off would have resulted in identical or very
      similar results for ADx and KIMS X and large increases in the false positives for
      AxSYM and EMIT and the false negatives for EMIT N and KIMS.

PMID- 16105262
TI  - Comparative alcohol concentrations in blood and vitreous fluid with illustrative
      case studies.
AB  - The Toxicology Bureau of the New Mexico Department of Health performs drug and
      alcohol testing on approximately 2800 medical examiner cases each year across the
      entire state. Although blood is usually the preferred specimen for alcohol
      analysis, the importance of multiple specimen analysis in alcohol-related death
      investigation is well understood. Quantitative alcohol determination in a variety
      of postmortem specimens may provide important interpretive information. In a
      total of 322 consecutive cases, blood and vitreous alcohol concentrations were
      compared. No alcohol was detected in either specimen in only 27 of the cases. In
      the remaining 295 investigations, alcohol was detected in the vitreous fluid,
      blood, or both. Analysis of the data and presentation of case studies reinforce
      the need for multiple specimen analysis in alcohol-related death investigation.
      Postmortem blood and vitreous alcohol concentrations were compared in a series of
      295 alcohol-positive cases. The vitreous alcohol concentration (VAC) exceeded the
      blood alcohol concentration (BAC) in 209 cases (71%). Blood alcohol
      concentrations exceeded vitreous concentrations in 81 cases (27%), and the
      concentrations were equivalent in 5 cases (2%). For the purpose of this study,
      samples that were negative in both specimens were excluded. In casework where the
      VAC > BAC, linear regression analysis indicated an R2 value of 0.958 (n = 209)
      and a VAC approximately 16% higher than the BAC. The VAC/BAC ratio was more
      variable at lower BACs (< 0.1 g/100 mL). The source of blood for this data set
      was predominantly femoral (n = 203), followed by heart (n = 5) and pleural cavity
      (n = 1). Although VAC/BAC ratios were more consistent at concentrations of 0.1
      g/100 mL and above, the overall ratio ranged from 1.01 to 2.20. Of the 81 cases
      where BAC > VAC, a total of 24 cases indicated no vitreous alcohol. The range of
      blood alcohol concentrations among these cases was widely variable (0.01 to 0.30
      g/100 mL). Unlike the VAC/BAC data set which consisted of 97% femoral blood, the
      source of blood in the BAC > VAC data set was slightly more variable. Of the 81
      cases where BAC > VAC the blood source consisted of femoral (n = 68), heart (n =
      8), pleural cavity (n = 2), carotid (n = 1), jugular (n = 1), and chest blood (n
      = 1). All analyses were conducted using dual-column gas chromatography with flame
      ionization detection (GC-FID) with a reporting limit of 0.01 g/100 mL ethanol in
      postmortem samples. A series of case studies are used to demonstrate postmortem
      interpretive issues and the benefits associated with multiple specimen analysis.
      Cases include postmortem production of ethanol, rapid or unexpected death during
      the absorptive phase, and site-dependent differences following traumatic injury.
      Actual case studies involving other volatile organic compounds are also presented
      including isopropanol and acetone from endogenous and exogenous sources. Many of
      these cases studies highlight the difficulty associated with postmortem alcohol
      interpretation in the absence of multiple specimens or adequate case history.

PMID- 16105263
TI  - Gas chromatography-high-resolution mass spectrometric method for determination of
      methamphetamine and its major metabolite amphetamine in human hair.
AB  - Gas chromatography-high-resolution mass spectrometric (GC-HRMS) method is
      presented for the qualitative and quantitative analysis of methamphetamine (MA)
      and its major metabolite, amphetamine (AMP), in human hair. The method procedure
      involves decontamination of hair with distilled water and acetone, acidic
      hydrolysis and extraction in the presence of the internal standard, and GC-HRMS
      selective ion monitoring (SIM) analysis. The limits of detection (LOD) were 9
      pg/mg for MA and 21 pg/mg for AMP using a 30-mg hair sample, and the SIM
      responses were linear with coefficients of correlation ranged from 0.9998 to
      0.9999. The recoveries were found to be 91.1-92.3%. By using HRMS (resolution of
      5000), detection sensitivity is improved because of the elimination of the
      biological background, and the LODs for MA and AMP were 2.4-4.4 times lower than
      those of low-resolution MS. The GC-HRMS method was successfully applied to the
      analysis of cosmetically treated hair, which is difficult to analyze with the
      conventional method.

PMID- 16105264
TI  - Urinary excretion rates of ketamine and norketamine following therapeutic
      ketamine administration: method and detection window considerations.
AB  - Ketamine is widely used in veterinary medicine. Its medical application in humans
      is limited to children because in adults it induces severe psychedelic episodes.
      In recent years, teenagers have abused ketamine as a recreational and "club drug"
      because of its hallucinogenic and stimulant effects. Ketamine is also misused as
      a "date-rape" drug (to induce amnesia in unsuspecting victims). Sensitive gas
      chromatography-mass spectrometry-negative chemical ionization (GC-MS-NCI) and
      liquid chromatography-mass spectrometry-atmospheric pressure chemical ionization
      (LC-MS-APCI) methods were applied for the simultaneous quantification of ketamine
      and its major metabolite, norketamine, in urine. Urine samples were collected
      from hospitalized children who had received ketamine as an anesthetic. Individual
      urine samples were collected up to 16 days after drug administration. Using the
      GC-MS-NCI method, ketamine was detected in the urine of the children from only
      the day of drug administration up to 2 days after drug administration. Its
      concentrations ranged from 29 to 1410 ng/mL. Norketamine (measured in
      concentrations of 0.1-1442 ng/mL) was detected up to 14 days. Using the LC-MS
      APCI method, norketamine was detected up to 6 days after drug administration,
      ranging in concentrations of 2-1559 ng/mL, while ketamine was detected up to 11
      days (2-1204 ng/mL). In the urine taken from one child, ketamine was not detected
      through the entire 16-day period using both methods. The detection window for the
      analytes is highly dependent on the method used for determination and varies
      between individuals.

PMID- 16105265
TI  - Determination of strychnine in human blood using solid-phase extraction and GC-EI
      MS.
AB  - A rapid, simple, and sensitive method has been developed for the identification
      and quantitation of strychnine in human blood. The sample cleanup procedure
      involved solid-phase extraction with Oasis(R) HLB cartridges. The extracts were
      analyzed by gas chromatography-electron impact ionization-mass spectrometry.
      Limits of detection (LOD) and quantitation (LOQ) were 0.03 and 0.10 microg/mL,
      respectively, and the method was found to be linear between the LOQ and 2.5
      microg/mL, with a correlation coefficient of 0.9994. Intra- and interday
      precision and accuracy were determined at both low and high concentrations (0.50
      and 2.00 microg/mL). The CVs ranged from 5.63 to 8.50% and bias was within +/-
      10% of the true value. Mean recovery of strychnine was 90.7%. Because of its
      simplicity and speed, the described method can be applied in forensic toxicology
      laboratories to determine this alkaloid in whole blood samples. Also, the fact
      that only 0.5 mL of blood is required to accomplish the analysis make this
      procedure useful in situations where several exams are needed and the sample
      volume is limited.

PMID- 16105266
TI  - An automated alcohol dehydrogenase method for ethanol quantification in urine and
      whole blood.
AB  - In a previous work, an automated alcohol dehydrogenase method for the
      quantification of ethanol in whole blood (blood) specimens was presented. In the
      present work the application of the method to urine specimens has been
      investigated. Also, method robustness to routine analysis of urine and blood
      specimens during a period of eight months is shown. The limits of detection and
      quantification for urine were 0.0012 g/dL and 0.0042 g/dL, respectively. Relative
      standard deviations for the repeatability and within-laboratory reproducibility
      were in the ranges 1.4-4.1% and 1.8-4.6%, respectively. The method was compared
      with two headspace gas chromatography-flame ionization detection methods using
      authentic forensic urine specimens (n = 305) and blood specimens (n = 3186).
      Passing-Bablok regression for the concentration range 0.01-0.48 g/dL (urine) and
      0.002-0.40 g/dL (blood) showed a statistically significant difference, for urine
      y = 0.9313 (0.9250 - 0.9377)x + 0.0038 (0.0029-0.0044) and for blood y = 0.9493
      (0.9491 - 0.9495)x + 0.0032 (0.00318-0.00323), at 95% confidence level. The
      results of the external quality control specimens were in accordance with the
      reported theoretical concentrations.

PMID- 16105267
TI  - Evaluation of the post-rotational nystagmus test (PRN) in determining alcohol
      intoxication.
AB  - This study evaluated the accuracy of the post-rotational nystagmus test (PRN) on
      the basis of the results of 1006 PRN tests performed at the Institute for
      Forensic Medicine in Ljubljana between 1998 and 2002 during standardized medical
      examinations in cases of suspected drunk driving. The evaluation of PRN test
      results with blood alcohol concentration (BAC) as a reference was based on
      classification into the following categories and characteristics: true positives
      (TP), true negatives (TN), false positives (FP), false negatives (FN),
      sensitivity, specificity, positive predictive values (PPV), negative predictive
      values (NPV), and accuracy. An optimal cut-off value of 10 s for post-rotational
      nystagmus time was chosen with the help of a receiver operating characteristic
      (ROC) curve for the BAC limit of 0.5 g/kg. The results of the decision analyses
      were: TP = 584, FP = 43, FN = 229, TN = 150, sensitivity = 0.718, specificity =
      0.777, PPV= 0.931, NPV= 0.396, and accuracy = 0.730. The area under the ROC curve
      (AUC) was 0.813. Based on the AUC, the post-rotational nystagmus test is a good
      test for predicting alcohol intoxication over 0.5 g/kg. As a part of the
      physician's examination, it contributes significantly to the description of the
      clinical state.

PMID- 16105268
TI  - Fatality due to acute alpha-methyltryptamine intoxication.
AB  - In February 2003, the Miami-Dade County Medical Examiner Department reported the
      first known death in the country related to alpha-methyltryptamine (AMT). AMT is
      an indole analogue of amphetamine investigated in the 1960s as an antidepressant,
      stimulant, and monoamine oxidase inhibitor. Today, AMT is recognized as a
      powerful psychedelic drug among high school and college-aged men and women. Its
      popularity is partly due to the multitude of anecdotal websites discussing AMT as
      well as its legality and availability for purchase via the Internet prior to
      April 2003. Emergency designation of AMT as a Schedule 1 controlled substance by
      the Drug Enforcement Administration occurred shortly after the death in Miami
      Dade County. The case in Miami involved a young college student who, prior to
      death, advised his roommate that he was "taking hallucinating drugs" and as a
      result had "discovered the secret of the universe". Approximately 12 h later, the
      roommate discovered the deceased lying in bed unresponsive. An empty 1-g vial of
      AMT was recovered from the scene and sent to the toxicology laboratory. Initial
      screening of urine by enzyme-multiplied immunoassay technique was positive for
      amphetamines, and the basic drug blood screen detected a small peak later
      identified by mass spectrometry as AMT. For quantitation, AMT was isolated using
      solid-phase extraction, derivatized with pentafluoropropionic anhydride, and
      analyzed using gas chromatography-mass spectrometry. Quantitative analysis was
      based upon m/z 276, 303, and 466 for AMT and m/z 306, 333, and 496 for the
      internal standard, 5-methoxy-alpha-methyltryptamine. A linear calibration curve
      from 50 to 500 ng/mL was used to calculate the concentration of AMT in the
      samples and controls. Blood, tissue, and gastric specimens were diluted to bring
      the observed concentration within the limits of the standard curve. Matrix
      matched controls were extracted and analyzed with each run. Postmortem iliac vein
      blood revealed 2.0 mg/L, gastric contents (48 g collected at autopsy) contained
      9.6 mg total of AMT, liver contained 24.7 mg/kg, and the brain contained 7.8
      mg/kg. An additional Medical Examiner case from another jurisdiction revealed 1.5
      mg/L in antemortem serum.

PMID- 16105269
TI  - Distribution of GHB in tissues and fluids following a fatal overdose.
AB  - Gamma-hydroxybutyrate (GHB) is encountered in biological specimens as an
      endogenous neuromodulator, recreational drug, or therapeutic agent. Clinically,
      the drug is useful for the treatment of cataplexy. Illicit doses are typically 2
      4 g, and the onset of action is rapid, occurring 15-30 min following oral
      ingestion. Dose-dependent effects include drowsiness, euphoria, dizziness,
      vomiting, respiratory depression, coma, and death. GHB was isolated from
      biological samples using a simple liquid-liquid extraction. The trimethylsilyl
      derivative (GHB-di-TMS) was analyzed using gas chromatography-mass spectrometry
      with positive chemical ionization. Deuterated internal standard and selective ion
      monitoring were used throughout. We report a GHB fatality involving a 35-year-old
      male who was partying with friends. Subjects at the party ingested unknown
      quantities of wine and GHB. A female companion at the party reported seeing the
      male alive before she herself passed out. She awoke to find the decedent cold and
      stiff. Postmortem specimens were submitted for comprehensive toxicology testing.
      No alcohol or common drugs of abuse were detected. A targeted analysis revealed
      GHB in urine, brain, vitreous fluid, femoral blood, heart blood, and liver at
      concentrations of 1665 mg/L, 102 mg/kg, 48 mg/L, 461 mg/L, 276 mg/L, and 52
      mg/kg, respectively. Concentrations of the drug in urine and vitreous fluid are
      important in death investigations because of significant postmortem production of
      GHB in blood specimens. The cause of death was attributed to GHB intoxication,
      and the manner of death was accidental.

PMID- 16105270
TI  - Postmortem distribution of tramadol, amitriptyline, and their metabolites in a
      suicidal overdose.
AB  - A case report involving a 34-year-old white male who was found dead at home by
      his roommate is presented. At the time of his death, he was being treated with
      tramadol/acetaminophen, metaxalone, oxycodone, and amitriptyline. The decedent's
      mother stated that he had been taking increasing amounts of pain medication in
      order to sleep at night. There were no significant findings at autopsy; however,
      toxicology results supported a cause and manner of death resulting from suicidal
      mixed tramadol and amitriptyline toxicity. This case reports the tissue and fluid
      distribution of tramadol, amitriptyline, and their metabolites in an acutely
      fatal ingestion in an effort to document concentrations of these analytes in 12
      matrices with respect to one another to assist toxicologists in difficult
      interpretations.

PMID- 16105271
TI  - Case studies of postmortem quetiapine: therapeutic or toxic concentrations?
AB  - The focus of this study was to determine if the analysis of a variety of
      postmortem biological specimens would aid in the toxicological interpretation of
      quetiapine in the cause and manner of death determinations. Postmortem quetiapine
      concentrations were examined in 21 medical examiner cases using liquid-liquid
      extraction and high-performance liquid chromatography analysis. Specimens
      analyzed were peripheral blood, central blood, liver, vitreous humor, and gastric
      contents, when available. Findings from this study suggest that therapeutic
      postmortem quetiapine concentrations may be less than 1 mg/L in both peripheral
      and central blood, less than 0.5 mg/L in vitreous, and less than 5 mg/kg in
      liver. Quetiapine concentrations indicative of toxicity were estimated at greater
      than 1 mg/L in peripheral and central blood, greater than 0.5 mg/L in vitreous,
      and greater than 5 mg/kg in the liver. Liver concentrations appeared to be
      particularly helpful in determining the potential for toxicity when compared with
      blood concentrations. Cases in which quetiapine was determined to play a
      significant role in the death indicated postmortem liver concentrations greater
      than 5 mg/kg. Cases in which quetiapine concentrations were considered incidental
      or noncontributory in the death had liver concentrations 2 mg/kg or less.

PMID- 16105272
TI  - Where will Benedict XVI lead his sheep?

PMID- 16105273
TI  - Passion, politics and pioneers: the fpa at 75.

PMID- 16105274
TI  - Treating endometriosis with the levonorgestrel-releasing intrauterine system:
      real hope or gimmick?

PMID- 16105275
TI  - Surgical abortion using manual vacuum aspiration under local anaesthesia: a pilot
      study of feasibility and women's acceptability.
AB  - OBJECTIVE: Studies from the USA have reported the efficacy and high acceptability
      of surgical abortion using manual vacuum aspiration (MVA) under local
      anaesthesia. The aim of this study was to assess the feasibility, acceptability
      and efficacy of surgical abortion using MVA under local anaesthesia for
      termination of pregnancy up to 63 days' gestation, within a UK National Health
      Service setting. METHODS: Surgical abortion was carried out using MVA under local
      anaesthesia. Women's satisfaction with the procedure, and pain and anxiety
      levels, were assessed. The main outcome measures were: (1) feasibility assessed
      through successful completion of the procedure without the need for general
      anaesthetic or conversion to suction vacuum aspiration, (2) efficacy assessed
      through complete uterine evacuation without the need for further medical or
      surgical intervention and (3) women's acceptability of the procedure. RESULTS:
      The mean (SD) gestation was 50 (9.4) days. A total of 55/56 (98%) women had a
      successful procedure and did not require any further surgical or medical
      treatment. Fifty-five (98%) women were satisfied with the procedure, 48 (86%)
      said they would recommend it to a friend and 45 (80%) said they would have the
      same method again in the future. Anxiety levels, as reflected by the visual
      analogue scales, showed a significant fall in anxiety scores following the
      procedure (p<0.01). CONCLUSIONS: Surgical abortion using MVA under local
      anaesthesia is effective and acceptable to women. These findings now need to be
      assessed in the context of a randomised trial.

PMID- 16105279
TI  - Home self-administration of misoprostol for medical abortion up to 56 days'
      gestation.
AB  - OBJECTIVE: Studies from the USA have suggested the feasibility and acceptability
      of home medical abortion, however the issue has not been addressed in the UK.
      This study aimed to assess the feasibility, efficacy and acceptability of home
      self-administration of misoprostol for medical abortion up to 56 days' gestation.
      METHODS: Mifepristone 200 mg was given orally in hospital under nursing
      supervision. Women were provided with misoprostol tablets 600 microg and advised
      to take them sublingually 36-48 hours later. The main outcome measures were (1)
      feasibility, assessed through successful completion of abortion at home without
      the need for hospital admission, (2) efficacy, assessed through complete uterine
      evacuation without the need for further medical or surgical intervention and (3)
      women's acceptability of the procedure as assessed by questionnaire. RESULTS: A
      total of 49 women participated in this study. Of these, 48 women aborted at home
      while one opted to be admitted to hospital after receiving misoprostol at home.
      One woman underwent surgical evacuation 5 weeks following abortion for excessive
      bleeding and retained products of conception. A total of 43/44 (98%) women were
      satisfied with having the abortion at home. Side effects experienced by women
      included nausea [32/40 (80%], vomiting [17/41 (42%)], diarrhoea [17/41 (42%)],
      shivering [26/40 (65%)], tiredness [32/40 (80%)], headache [12/39 (31%)], hot
      flushes [14/40 (35%)], dizziness [24/39 (62%)] and unpleasant mouth taste [19/38
      (50%)]. CONCLUSIONS: This study suggests the feasibility and acceptability of
      home self-administration of misoprostol for medical abortion up to 56 days'
      gestation. These findings need to be assessed in the context of a randomised
      trial.

PMID- 16105282
TI  - Community-based distribution and contraception usage in Iran.
AB  - OBJECTIVE: Despite the availability of free contraception from family planning
      clinics, the rate of unwanted pregnancy in Iran is still high. The effectiveness
      of other methods for contraceptive supply should, therefore, be evaluated. The
      aim of this study was to determine the effects of community-based distribution
      (CBD) on contraceptive usage in Iran. METHODS: This controlled field trial study
      involved 297 individuals (100 subjects in the CBD group and 197 subjects in the
      control group) from four major remote areas of Hamedan, Iran. Stratified random
      sampling was used. RESULTS: Data analysis suggested that using CBD has four major
      effects: (1) it increases the level of contraceptive knowledge (p<0.0001), (2) it
      enhances correct contraceptive choice by couples (p<0.0001), (3) it improves
      contraceptive usage (p<0.0001) and (4) it improves contraceptive continuation
      rates (p<0.0001). CONCLUSIONS: CBD facilitates better knowledge, proper choice,
      and correct and continuous usage of contraception. This method should, therefore,
      be adopted for family planning services in remote areas of Iran.

PMID- 16105283
TI  - Diversity in the use of pregnancy-related care among ethnic groups in Guatemala.
AB  - OBJECTIVE: This study investigated ethnic differentials in the use of pregnancy
      related care and aimed to identify whether the differences persist when
      geographical access to services is equal. This study was based in the north
      eastern Ch'orti area of Guatemala, an area characterised by a mixed ladino (of
      Spanish descent) and Maya (Ch'orti) culture. METHODS: Data from a household
      survey carried out in 2001 in the town of Jocotan, and a previous survey carried
      out in 1994 in two nearby indigenous villages (aldeas), were used in this study.
      Logistic regression was used to explore the data. Unlike the Demographic and
      Health Survey (DHS) (1998-1999) that classifies ethnic groups according to dress
      and language, this study introduced an alternative approach based on self
      identification. RESULTS: The results showed significant differences and a
      gradient in the use of modern pregnancy care services among self-identified
      ethnic groups within the same town, after controlling for socioeconomic and
      cultural indicators. Women of 'mixed' ethnicity had an intermediate behaviour
      between ladino and indigenous women. Women in the nearby aldeas almost solely
      relied on the traditional birth attendant for pregnancy-related care. The DHS
      data did not permit the detection of ethnic diversity in the use of pregnancy
      care for this region. CONCLUSIONS: Differences in the use of modern pregnancy
      care exist even among self-identified ethnic groups with no outward markers of
      ethnicity and persist when access to services is equal. For the majority of the
      population, living in indigenous villages, pregnancy care remains traditional.
      This ethnic diversity highlights the importance of further extending affordable,
      high-quality and culturally adapted maternal health care services in Guatemala.

PMID- 16105284
TI  - Communication, ideation and contraceptive use in Burkina Faso: an application of
      the propensity score matching method.
AB  - OBJECTIVE: The study aim was to assess the effects of a multi-component
      communication campaign that promoted contraceptive use in Burkina Faso. METHODS:
      This was a cross-sectional survey conducted in 2001 involving 1421 women of
      reproductive age from Ouagadougou and Bobo-Dioulasso. Participants during the
      2001 survey were randomly selected from 54 enumeration areas that were covered
      during the 1999 Demographic and Health Survey. The propensity score matching
      (PSM) technique was the analytical method used to assess the effects of the
      campaign. RESULTS: More than three-quarters of the respondents reported exposure
      to at least one example of campaign material. Compared with no exposure, high
      campaign exposure is associated with an adjusted increase of 21.8 percentage
      points in the proportion of women currently using modern contraceptive methods.
      Similarly, low exposure is associated with a 7.3 percentage point increase over
      no exposure. The campaign is also associated with increased knowledge about
      contraceptives and more favourable attitudes towards family planning.
      CONCLUSIONS: The multiple-component nature of the campaign makes it easy for many
      members of the target audience to hear consistent messages from a variety of
      sources. This is a key element responsible for the documented effectiveness of
      the campaign. Despite its limitations, the PSM technique is a straightforward
      method that should be used more often to assess the effects of communication
      programmes.

PMID- 16105286
TI  - Sexual health care training needs of general practitioner trainers: a regional
      survey.
AB  - OBJECTIVES: The National Strategy for Sexual Health and HIV aims to facilitate
      improved patient access to sexual health care, primarily in general practice.
      This study aimed to identify sexual health care provision in general practitioner
      (GP) training practices and highlight training and resource implications of the
      strategy for GPs and prospective GPs. METHODS: Data were gathered from interviews
      with five key representatives (all of whom had a special interest in GP training
      and/or sexual health care) and a self-completed questionnaire survey of all 374
      GP trainers in the West Midlands region. The questionnaire was developed from the
      interviews and comprised three sections: sample characteristics; current
      practice; and 30 statements to elicit attitudes, knowledge and training
      implications. The questionnaire was mailed out in March 2002 with two re-mailings
      at 2-week intervals. RESULTS: Most GP trainers (79%; n=295) returned completed
      questionnaires. Most respondents were already offering some 'Level 1 services' or
      were prepared to including cervical screening (100%; n=295), sexual history
      taking (95%; n=271), sexually transmitted infection (STI) testing (74%; n=217),
      HIV testing (68%; n=198) and contraceptive services (71%; n=208). However, most
      (86%; n=251) needed further information on the Strategy detail and its
      implications. Training needs in sexual history taking, STI testing and HIV
      testing were also highlighted. Most GP trainers (62%; n=181) believed GP
      registrars were relatively unprepared for sexual health care and proposed
      improved training and assessment. Appropriate nurse training should also be
      provided. CONCLUSION: Although 82% (n=242) of respondents would implement the
      Strategy if properly resourced, considerable training and support needs were
      identified.

PMID- 16105287
TI  - Pilot studies in family planning and reproductive health care.

PMID- 16105288
TI  - Questionnaires: paradigms and pitfalls.

PMID- 16105289
TI  - FFPRHC Guidance (July 2005): The use of contraception outside the terms of the
      product licence.
AB  - This Guidance provides information for clinicians and women considering the use
      of contraception outside the terms of the product licence. A key to the grades of
      recommendations, based on levels of evidence, is given at the end of this
      document. Details of the methods used by the Clinical Effectiveness Unit (CEU) in
      developing this Guidance and evidence tables summarising the research basis of
      the recommendations are available on the Faculty website (www.ffprhc.org.uk).
      Abbreviations (in alphabetical order) used include: CEU, Clinical Effectiveness
      Unit; COC, combined oral contraception/contraceptive; DMPA, depot
      medroxyprogesterone acetate; ENG, etonogestrel; IUD, copper-bearing intrauterine
      contraceptive device; LNG-IUS, levonorgestrel-releasing intrauterine system; NET
      EN, norethisterone enantate; PGD, Patient Group Direction; PIL, Patient
      Information Leaflet; POC, progestogen-only contraception/contraceptive; POEC,
      progestogen-only emergency contraception; POP, progestogen-only pill; RCT,
      randomised controlled trial; SPC, Summary of Product Characteristics; UPSI,
      unprotected sexual intercourse; WHO, World Health Organization; WHOMEC, WHO
      Medical Eligibility Criteria for Contraceptive Use; WHOSPR, WHO Selected Practice
      Recommendations for Contraceptive Use.

PMID- 16105291
TI  - Self-help books.

PMID- 16105292
TI  - What is your duty of care?

PMID- 16105294
TI  - Self removal of Implanon: a case report.

PMID- 16105303
TI  - Faculty statement from the CEU and fpa 'Your Guide to the Combined Pill' leaflet,
      April 2005, based on the WHO's 2004 Guidance re advice for missed COCs.

PMID- 16105305
TI  - Missed pills.

PMID- 16105306
TI  - CEU statement on missed pills.

PMID- 16105307
TI  - fpa leaflet on the combined pill.

PMID- 16105308
TI  - Chlamydia screening in general practice: a missed opportunity?

PMID- 16105310
TI  - Emergency contraception for women aged over 40 years.

PMID- 16105311
TI  - When is a pill missed?

PMID- 16105312
TI  - Stop 'QOFing' and moaning; start lobbying!

PMID- 16105313
TI  - Spinal fracture in a young Depo-Provera user.

PMID- 16105314
TI  - Cerazette for premenstrual tension.

PMID- 16105319
TI  - Cancer mortality in Latin America: implications for prevention.

PMID- 16105320
TI  - Cancer incidence among Hispanic children in the United States.
AB  - OBJECTIVE: To directly compare cancer incidence among Hispanic children and non
      Hispanic white children in California and Florida, two states in the United
      States of America that include nearly one in three Hispanic children in the
      country. METHODS: Cross-sectional data for 1988 through 1998 pertaining to all
      incident pediatric cancer cases (age < 15 years) with race/ethnicity coded as
      either Hispanic or non-Hispanic white came from the Florida Cancer Data System
      database and the California Cancer Registry database. The results were expressed
      as age-standardized incidence rates, standardized to the world standard million
      population. Hispanic rates and non-Hispanic white rates were compared using
      standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs.).
      RESULTS: The SIR for all cancers for Hispanic children compared to non-Hispanic
      white children was 1.02 (95% CI: 0.99, 1.05). For selected tumor types, SIRs
      indicated higher incidences among Hispanic children for leukemia (SIR = 1.26; 95%
      CI: 1.19, 1.34), Hodgkin's lymphoma (SIR = 1.29; 95% CI: 1.08, 1.54), and germ
      cell tumors (SIR = 1.62; 95% CI: 1.34, 1.96). There were lower incidences for the
      Hispanic children for central nervous system tumors (SIR = 0.72; 95% CI: 0.66,
      0.78) and for sympathetic nervous system tumors (SIR = 0.76; 95% CI: 0.66, 0.87).
      In terms of interstate differences, the incidence of lymphoma, central nervous
      system tumors, sympathetic nervous system tumors, and malignant bone tumors was
      highest among Hispanic youth in Florida; the incidence of hepatic tumors was
      highest among Hispanic youth in California. CONCLUSIONS: While the overall cancer
      incidence rate among Hispanic children was similar to that for non-Hispanic white
      children, significant differences for specific tumor types were identified. Since
      Hispanic ethnicity may be a confounder for other cancer risk factors (e.g.,
      familial, socioeconomic, or environmental), it is recommended that future
      research into Hispanic pediatric cancer risk investigate these risk factors.

PMID- 16105321
TI  - [Predictive factors for noncompliance with tuberculosis treatment in an endemic
      region of Peru].
AB  - OBJECTIVE: To identify factors that predict noncompliance with tuberculosis
      treatment in the province of Ica, Peru. METHODS: Between 1998 and 2000 a case
      control study (1:1 ratio) was conducted in the province of Ica, with 55 cases
      (persons who dropped out of treatment) being identified. The factors evaluated
      were chosen from Lalonde's model of the field of health. The respective odds
      ratios were calculated by means of univariate analysis and multivariate analysis.
      RESULTS: The following factors were identified as being predictive of
      noncompliance with tuberculosis treatment: thinking that the information that
      health workers provided on treatment was insufficient (odds ratio (OR) = 4.20;
      95% confidence interval (95% CI), 1.77-10.02), thinking that the office hours for
      receiving treatment were inadequate (OR = 9.95; 95% CI, 1.97-50.21), and
      consuming illegal drugs (OR = 7.15; 95% CI, 1.69-30.23). CONCLUSIONS: To improve
      compliance with tuberculosis treatment, it is necessary to provide patients with
      personalized information on the disease and its treatment, and to offer them
      flexible, appropriate times to receive treatment. Drug consumption is the most
      serious risk factor for noncompliance, and identifying and following up with drug
      users is crucial.

PMID- 16105322
TI  - [The occurrence of vaccine-associated paralytic poliomyelitis in Brazil, 1995 to
      2001].
AB  - OBJECTIVE: To describe the occurrence of vaccine-associated paralytic
      poliomyelitis (VAPP) in Brazil between 1995 and 2001 and to determine the level
      of risk for this adverse event. METHODS: This retrospective study utilized data
      from acute flaccid paralysis investigation and notification records from the
      Ministry of Health in Brazil. Cases were defined as individuals with a diagnosis
      of acute flaccid paralysis and a positive stool culture or sequelae compatible
      with poliomyelitis appearing up to 60 days after the beginning of motor
      impairment. Also included were individuals in any age range who had contact with
      vaccinated persons between the 4th and 40th day before the onset of the disease
      and who developed motor impairment between 4 and 85 days after this contact. Risk
      was calculated as the ratio between the number of cases and the respective number
      of doses given in a year, according to the National Immunization Program.
      RESULTS: Ten cases of VAPP were recorded in the period. The mean age of the cases
      was 4.7 months. Four cases were associated with the first dose, four with the
      second dose, and two cases were attributed to contact. In two cases type 1 virus
      was identified; in one case, type 2; and in three cases, type 3. More than one
      serotype was isolated in four cases. In all 10 cases the serotype was determined.
      The observed risk for VAPP during the period studied was 1:5.11 million when
      considering only the first dose and 1:10.67 million for all the doses.
      CONCLUSION: The main technical and ethical dilemma of the post-poliomyelitis
      elimination stage is the occurrence of paralytic cases that result from the
      vaccine policy itself, whose objective is the eradication of polio.

PMID- 16105323
TI  - [Erythrocyte defects and parasitemia density in patients with Plasmodium
      falciparum malaria in Buenaventura, Colombia].
AB  - OBJECTIVES: To determine the prevalence of some erythrocyte defects and to
      evaluate the relation that that has with parasitemia density in individuals
      diagnosed with Plasmodium falciparum malaria in a population in the Pacific
      coastal region of Colombia. METHODS: This prevalence study was carried out with
      242 persons with P. falciparum malaria who had gone for consultation at the
      Program of Tropical Diseases diagnostic center in the city of Buenaventura,
      Colombia. The parasitemia levels were measured, and also determined was the
      presence of congenital erythrocyte defects (glucose-6-phosphate dehydrogenase
      (G6PD) deficiency, abnormal hemoglobins, and thalassemias) and of other factors
      possibly related to parasitemia levels. RESULTS: The prevalence of erythrocyte
      defects was 26.4% (95% confidence interval, 21.0%-32.5%), which was similar to
      what had been found in previous studies in the same area of Colombia. In the
      multiple regression models, individuals with sickle cell anemia or a complete
      deficiency of G6PD had a lower density of parasitemia than did persons without
      any erythrocyte defect. After adjusting for other variables of interest, the risk
      of high parasitemias was lower in persons with sickle cell anemia (odds ratio =
      0.30) and individuals with a complete deficiency of G6PD (odds ratio = 0.72).
      CONCLUSIONS: Our results confirm the high prevalence of erythrocyte defects in
      Colombia's Pacific coastal region, in a population with ethnic characteristics
      that are similar to those of some populations in West Africa. Our results also
      lend support for the existence of innate resistance to malaria among carriers of
      hemoglobin AS and in persons with G6PD deficiency.

PMID- 16105324
TI  - Dispelling disaster myths about dead bodies and disease: the role of scientific
      evidence and the media.
AB  - For decades, after nearly every natural disaster, fear of disease has encouraged
      communities, local authorities, and governments to rapidly dispose of the bodies
      of the victims without first identifying them. In May 2004 this journal published
      the first-ever review article to comprehensively assess the scientific evidence
      on the infectious disease risks of dead bodies following natural disasters, along
      with an editorial commenting on the persistence of myths concerning the dangers
      allegedly posed by dead bodies. This paper assesses the impact that the review
      article and the editorial have had on the way that health risks from dead bodies
      have been reported by the media over the following year, especially focusing on
      the South Asian tsunami disaster of December 2004. While some media outlets have
      reported erroneous information, hundreds of other news stories have accurately
      reported that dead bodies pose no public health risk, and have explained the
      priority for properly identifying the deceased. Nevertheless, publication of
      scientific evidence alone is insufficient to bring about public health action.
      International agencies need to continue their work on producing standards,
      guidelines, and practical guidance on managing dead bodies. There needs to be a
      community-centered approach to informing communities about the management of the
      dead following disasters and the rights of individuals to be treated respectfully
      after death. Nongovernmental organizations should be encouraged to provide
      expertise and technical support in identifying and burying large numbers of dead.
      There also needs to be ongoing assessment of the technical processes involved in
      the recovery, identification, and disposal of dead bodies, as well as the
      effectiveness of disaster preparedness plans and communication with the affected
      population.

PMID- 16105325
TI  - Creating options in family planning for the private sector in Latin America.
AB  - The countries of Latin America and the Caribbean are facing the gradual phase-out
      of international-donor support of contraceptive commodities and technical and
      management assistance, as well as an increased reliance on limited public sector
      resources and a limited private sector role in providing contraceptives to the
      public. Therefore, those nations must develop multisectoral strategies to achieve
      contraceptive security. The countries need to consider information about the
      market for family planning commodities and services in order to define and
      promote complementary roles for the public sector, the commercial sector, and the
      nongovernmental-organization sector, as well as to better identify which segments
      of the population each of those sectors should serve. While it is unable to
      mandate private sector participation, the public sector can create conditions
      that support and promote a greater role for the private sector in meeting the
      growing needs of family planning users. Taking steps to actively involve and
      expand the private sector's market share is a critical strategy for achieving a
      more equitable distribution of available resources, addressing unmet need, and
      creating a more sustainable future for family planning commodities and services.
      This paper also discusses in detail the experiences of two countries, Paraguay
      and Peru. Paraguay's family planning market illustrates a vibrant private sector,
      but with limited access to family planning commodities and services for those who
      cannot afford private sector prices. In Peru a 1995 policy change that sought to
      increase family planning coverage had the effect of restricting access for the
      poor and leaving the Ministry of Health unable to pay for the growing need for
      family planning commodities and services.

PMID- 16105326
TI  - [The People's Health Movement: health for all now].
AB  - We are moving away from the year 2000, and the goal of "health for all" remains
      distant. Economic globalization, which many consider to be one of the most
      serious threats to health, moves ahead, along with globalization of international
      health policies. A small number of powerful actors are in charge of setting the
      agenda, and they relegate to an inferior position the World Health Organization,
      which has moved away from the goal of "health for all." All of this has helped to
      promote a neoliberal mentality in the field of health. The People's Health
      Movement was created with the objective of reestablishing the right to
      comprehensive health and to development with equity as principal priorities of
      health policies at the local, national, and international levels. The People's
      Health Movement uses as a strategy the People's Charter for Health, which was
      approved at the first People's Health Assembly, which was held in Bangladesh in
      2000. The Charter expresses collective concerns and the belief in a better and
      healthier world as a meeting point in order to promote a world health movement
      and a call for radical action. In July 2005 the People's Health Movement will
      hold the People's Health Assembly 2, in the city of Cuenca, Ecuador. The slogan
      of that meeting will be "The voices of the earth are calling!--let's build a
      healthy world." Among the topics that will be examined at the meeting are: health
      as a fundamental human right; militarization and occupation; environmental
      degradation; emerging and reemerging pandemics; equity, poverty, and health; the
      importance of cultural diversity; social and political violence; health in the
      hands of the people; health at work; traditional medicine and bioenergetic
      medicine; gender; and health sector reform. The objective of the People's Health
      Movement is to help to reach the Millennium Development Goals and to smooth the
      path toward attaining health for all, in Latin America and the Caribbean as well
      as in the rest of the world.

PMID- 16105327
TI  - A participatory assessment to identify strategies for improved cervical cancer
      prevention and treatment in Bolivia.

PMID- 16105329
TI  - [Neoliberal health reforms in Mexico].

PMID- 16105328
TI  - Refining the assessment of the sensitivity and specificity of diagnostic tests,
      with applications to prostate cancer screening and non-small cell lung cancer
      staging.

PMID- 16105330
TI  - The problem of unsafe abortions.

PMID- 16105331
TI  - Safe abortion: a woman's right.
AB  - Complications of induced abortion sadly remain significant causes of maternal
      mortality and morbidity around the world, but only in countries that do not
      provide access to safe abortion services. This article presents a brief account
      of how high maternal mortality from induced abortion became history in the UK and
      the dire consequences to women's health that unsafe abortion still has in many
      countries of the world. It gives a brief overview of the methods available to
      evacuate the uterus, with particular reference to manual vacuum aspiration. The
      status of the law in different countries is discussed, together with the need for
      health professionals to interpret repressive laws in ways that enables them to
      care for women who seek their help. Safe abortion services are cost effective,
      essential services for women. Men are part and parcel of the reason women resort
      to terminating a pregnancy, and, together with the countless children whose lives
      are dependent on a healthy caring mother, are also beneficiaries of safe abortion
      services. There can be no excuse for continuing to deny these services to so many
      women around the world.

PMID- 16105332
TI  - Abortions in adolescents.
AB  - This review discusses the problem of abortion in adolescents across the world and
      highlights the gaps in knowledge. It also examines the need for adolescent
      friendly services.

PMID- 16105333
TI  - A randomized trial of pain relief in termination of pregnancy in South Africa.
AB  - The aim of this prospective trial was to evaluate and compare paracervical block
      with diclofenac for pain relief during manual vacuum aspiration (MVA) for
      surgical termination of pregnancy. Participants were randomized into three
      groups, viz. group (i) diclofenac 75 mg intramuscularly (i.m.) 30 min before the
      procedure; (ii) diclofenac 75 mg i.m. 30 min before the procedure, together with
      local infiltration of the cervix with lignocaine 1% (10 mL); (iii) diclofenac 75
      mg i.m. 30 min before the procedure together with local infiltration of the
      cervix with lignocaine 1% (10 mL) and paracervical block with lignocaine 1% (5
      mL). There was a significant difference in pain scores during the procedure
      between groups (i) and (ii) (P < 0.001), and between groups (i) and (iii) (P <
      0.001) in pain scores during the procedure. There was no difference in pain score
      between groups (ii) and (iii) (P = 0.144). Post procedure analysis of pain score
      also showed significant difference between group (i) on one hand, and groups (ii)
      and (iii) (P < 0.001), but no significant difference between groups (ii) and
      (iii)(P = 0.029). The local anaesthetic infiltration of the cervix in combination
      with diclofenac or together with diclofenac and paracervical block provides
      better pain relief during and after the MVA.

PMID- 16105334
TI  - Profile of women with abortion complications in Ghana.
AB  - A cross-sectional study of 150 women was performed at the gynaecology department
      of the Korle-BuTeaching Hospital to describe the characteristics of patients with
      complications of induced or spontaneous abortions, and to find out the reasons
      behind induced abortions. In all, 31% of the study sample presented with
      complications of induced abortions. This group was younger, of lower parity, more
      educated, with lower economic potential, in less stable relationships and with a
      higher knowledge of modern contraceptive methods than the group with spontaneous
      abortions. The chief reason for procuring an induced abortion was the presence of
      relationship problems with the subject's partner. We conclude that measures to
      prevent induced abortions and their subsequent problems will yield major results
      if directed at women in their early 20s with at least primary education, no
      children, low economic potential, not in a stable relationship and who have had a
      previous induced abortion.

PMID- 16105335
TI  - Clinical and parasitological aspects of onchocercal skin diseases in Nigeria.
AB  - An assessment of onchocercal skin disease (OSD) conducted in 38 rural communities
      in the Imo River Basin, Nigeria, between March 1999 and September 2000, showed
      that depigmentation (DPM) was the most prevalent lesion in persons with skin
      microfilariae (mf) (26.3%), followed by chronic papular onchodermatitis (CPOD)
      (18.1%) and acute papular onchodermatitis (APOD) (15.5%). There was no
      significant difference (P > 0.05) in sex-related prevalence of OSD. While CPOD,
      lichenified onchodermatitis (LOD) and DPM were more prevalent in subjects over 30
      years old, APOD was associated more with those aged less than 30 years. OSD
      occurred with concomitant itching in nearly 50% of subjects. The geometric mean
      intensity of infection was 13 mf/mg per skin snip.

PMID- 16105336
TI  - Medical interns knowledge of TB in Pakistan.
AB  - Of 460 interns from five Pakistani teaching hospitals surveyed, only 22%
      correctly identified the estimated number of new TB cases in Pakistan. The
      majority (96%) knew that droplet infection was the usual mode of transmission.
      Only 38% considered sputum smears for acid-fast bacilli as the best test for
      diagnosis of pulmonary TB and 43.5% for follow-up during TB treatment. The
      recommended four-drug anti-TB regimen was prescribed by 56.5% in the initiation
      phase and the recommended two-drug combination in the continuation phase by 52%.
      Most interns (82%) were unable to identify a single component of directly
      observed treatment short course (DOTS) strategy. Our study reflects poor
      awareness of and low compliance to the World Health Organization/National
      Tuberculosis Programme guidelines among interns. For effective control of TB,
      immediate action to improve undergraduate and continuing medical education is
      essential, with special emphasis on national guidelines.

PMID- 16105337
TI  - Oral health-care workers and HIV infection control practices in Nigeria.
AB  - The first case of HIV infection was reported in Nigeria in 1986. Since then, the
      prevalence has risen from less than 0.1% in 1987 to 5.8% in 2002, and an
      estimated 3.6 million Nigerians now live with HIV/AIDS. More than 40 oral
      manifestations of HIV infection have been recorded and between 70% and 90% of
      persons with HIV infection will have at least one oral manifestation at sometime
      during the course of their disease. Oral health-care workers (OHCWS) are expected
      to play active roles in the prevention and control of HIV/AIDS. In this study, a
      one-day workshop was organized for 64 oral health workers in Ile-Ife, Nigeria,
      focusing on the epidemiology of HIV/AIDS, the oral manifestations, control and
      prevention of HIV in a dental environment, oral care of the infected patient and
      the ethical, legal and social aspects of HIV/AIDS. Participants' knowledge and
      practices of infection control were assessed with an infection control checklist
      administered pre- and post-workshop. Sixty (90.8%) respondents believed that
      HIV/AIDS was not yet a problem in Nigeria, and 58 (90.6%) believed that drugs
      have been developed which can cure HIV infection and AIDS. The men complied more
      with waste disposal regulations than women (P = 0.010). Twenty-nine of 58 (50.0%)
      did not discard gloves which were torn, cut or punctured. Seven (12.1%) did not
      change gloves between patients' treatment. Conscious efforts should be made to
      train OHCWS on all aspects of HIV/AIDS prevention and care. It must never be
      assumed that adequate information will be acquired through tangential sources.

PMID- 16105338
TI  - Quality surgical care for rural dwellers: the visiting option.
AB  - Although the majority of Africans live in rural areas, the existing surgical
      infrastructure and expertise are concentrated in urban centres. Many rural
      dwellers dislike visiting urban hospitals due to poverty, ignorance, fear,
      distance or unpleasant city experience. Trained personnel are unwilling to work
      in rural areas because of poor infrastructure and lack of incentive. The best
      means of bringing surgical care to rural dwellers is yet to be determined. We
      explored the visiting surgeon option. For three days every 4-6 weeks, a general
      surgeon visited a rural health centre in the Maiyama Local Government area of
      Kebbi State, Nigeria, and operated on selected surgical cases. In total, 111
      patients had 125 surgical procedures during 18 visits (January 2001-May 2003).
      These represented 66.7% of all surgical cases seen during the visits. There were
      22 (17.6%) paediatric surgical, 90 (72%) general surgical and 13 (10.4%)
      obstetric and gynaecological (O&G) cases. Fourteen (11.2%) procedures were
      performed as emergencies. The most common operation was inguinal herniorraphy,
      which constituted 36% of cases. The morbidity rate was 1.6% with no operative
      mortality. Easily treatable but potentially fatal surgical conditions are common
      among poor, rural dwellers. A visiting service can offer this population
      sustainable, cheap, good-quality care in a friendly environment.

PMID- 16105339
TI  - Perception and attitude to epilepsy among teachers in primary, secondary and
      tertiary educational institutions in middle belt Nigeria.
AB  - Compared with the disability associated with repeated seizures or side-effects of
      antiepileptic medications, the social stigma associated with epilepsy is often a
      major handicap to people living with this condition. This study therefore looked
      at the knowledge, attitude and perception of teachers who see a lot of
      epileptics, relates on daily bases and have a high influence on students with
      epilepsy.Self-administered questionnaires were used to obtain information from
      460 randomly selected teachers in primary, secondary and tertiary educational
      institutions in Kwara State-middle belt of Nigeria. The response rate was 75%.
      Almost all of the teachers had heard about epilepsy, but their awareness does not
      equate with the acceptance and understanding of epilepsy. About 30.5% believed
      that it could be contracted through the saliva of an epileptic, 27.7% thought it
      was synonymous with possession with evil spirit, while 10% misunderstood epilepsy
      for insanity. Close to one-fifth of the teachers were of the opinion that
      epileptic students have a below average mental capacity compared with other
      students and so cannot attainment the highest possible education. Negative
      attitude and bias towards epilepsy is still deeply ingrained among teachers in
      Nigeria. Apart from formal education, teachers need to have health education
      courses on common disease conditions such as epilepsy that are prevalent in
      school age. This might help to reduce prejudice and increase the acceptance of
      epileptic individuals into the classroom.

PMID- 16105340
TI  - The use of an internal oblique aponeurotic flap for tension-free reinforcement of
      the posterior inguinal wall: a new technique.

PMID- 16105341
TI  - Unsafe abortion in Kenya.

PMID- 16105342
TI  - Prevalence of rheumatic fever and rheumatic heart disease in rural Bangladesh.
AB  - A community-based study was done on 5923 rural Bangladeshi children aged 5-15
      years to determine the prevalence of rheumatic fever (RF) and rheumatic heart
      disease (RHD). The prevalence was found to be 1.2 (95% confidence interval 0.3
      2.1) per 1000 for RF defined by revised Jones criteria and 1.3 (0.4-2.2) per 1000
      for Doppler echocardiography-confirmed RHD.

PMID- 16105343
TI  - Attitudes of traditional healers towards Western medicine in rural Cameroon.
AB  - A range of AIDS prevention programmes suggested that cooperation between
      traditional healers and the biomedical primary health-care system would benefit
      patients. To assess the knowledge and attitudes of traditional healers in
      Cameroon towards Western medicine and evaluate their willingness to cooperate
      with the district health-care system, a qualitative study was undertaken. In this
      study, 16 randomly chosen traditional healers in Kumba, Cameroon, were
      interviewed. Western medicine was well accepted for certain indications and
      referral of patients to health-care centres was frequently practised. All healers
      stated that they wished to cooperate more extensively with the district primary
      health-care system and to obtain more biomedical knowledge. Closer cooperation
      between traditional healers and the district primary health-care system is
      possible. The frequent occurrence of illiteracy must be considered when designing
      health education for traditional healers.

PMID- 16105344
TI  - Improving medicine usage through patient information leaflets in India.
AB  - The impact of patient information leaflets (PILs) was measured in an outpatient
      department of a large tertiary care public health facility in India. Patients
      were allocated to control (114) or intervention group (118). Patients in the
      intervention group received PILs. The primary indicators [mean +/- standard
      deviation (SD)] improved significantly in the intervention group compared with
      the control group (15.7 +/- 7.3 versus 12.2 +/- 5.4). A three-fold (P < 0.01)
      increase in the awareness of the supplementary scores was observed in the
      intervention group (9.5 +/- 5.2 versus 3.3 +/- 2.7) compared with the control
      group (3.5 +/- 2.8 versus 3.5 +/- 2.8). Confounding variables, viz. age, sex,
      literacy level, did not influence the patients' knowledge. When the number of
      drugs prescribed increased, the patient's knowledge decreased significantly (P <
      0.0001). PILs provided to the patients by the pharmacist significantly improved
      knowledge about medication, and improved compliance at home.

PMID- 16105345
TI  - The problems of indeterminate HIV results in blood transfusion services in
      Nigeria.
AB  - Five hundred sera samples were collected from individuals whose age range was 16
      40 years, analysed using Murex 1 and 2 and Capillus HIV kit (Cambridge
      Biotechnology, Cambridge, UK), and confirmed with Western Blot technique
      (Biorad). Of these, 186 (37.2%) were repeatedly reactive, 90 (48.4%) were
      confirmed positive, 55 (29.6%) indeterminate (20 [10.7%] from blood donors) and
      44 (22.0%) were negative. The data reveal a significant correlation between
      indeterminate results and confirmed positive sera (P < 0.05). This demonstrates
      the high incidence of indeterminate HIV results encountered in blood transfusion
      services.

PMID- 16105346
TI  - Changing patterns of Kaposi's sarcoma in Nigerians.
AB  - This is a five-year retrospective study of 32 histologically diagnosed cases of
      Kaposi's sarcoma (KS) who had undergone HIV antibody testing at the Jos
      University Teaching Hospital: 13 cases (40%) were HIV-negative. Multiple lesions
      were more common in HIV-positive cases and affected unusual sites such as the
      face, oropharynx, conjuctiva, vulva and rectum in addition to the limbs and
      trunk, which were more frequently involved in HIV-negative cases. This pattern of
      KS seen in Nigerian patients shows similarities with other African countries
      which have been affected by the HIV epidemic.

PMID- 16105347
TI  - Liver cirrhosis: Child-Pugh grading of cases seen in Nigeria.
AB  - Child-Pugh grading is an important determinant of treatment options, surgical
      interventions and prognosis in chronic liver disease. Sixty-four liver cirrhosis
      patients (49 men, 15 women) seen at Ile-Ife, Nigeria were graded according to the
      Child-Pugh parameters. Only one (1.6%) was in Class A, while 21 (32.8%) and 42
      (65.6%) were in Classes B and C, respectively. Thirty-four either had
      coagulopathy or were already in encephalopathy at the time of presentation.
      Hepatitis B virus-associated disease was present in 64% of the patients. Most
      Nigerian cirrhosis patients present with very advanced disease; they are thus
      poor-risk candidates for diagnostic procedures and surgery. Efforts should be
      intensified at making the diagnosis at a much earlier stage and universal
      immunization with the hepatitis B vaccine should be commenced to reduce the
      incidence of HBV-related chronic liver disease in Nigeria.

PMID- 16105348
TI  - Blood loss at fibroids surgery: myomectomy versus total abdominal hysterectomy.
AB  - Two hundred and fifty patients with uterine fibroids were reviewed to compare
      operative outcomes and blood loss.

PMID- 16105349
TI  - Prolapsed intervertebral disc with sciatica: the role of common peroneal nerve
      block.
AB  - A total of 210 patients of Lumbar disc prolapse with sciatica were given common
      peroneal block by infiltrating 2% xylocaine around the common peroneal nerve 3 cm
      below the head of fibula on the affected side. After receiving the block the pain
      decreased on from grade 2.99 +/- 0.46 to 0.91 +/- 0.99, and straight leg raising
      increased from 32.1 +/- 12.55 to 59.66 +/- 12.11 degrees. The method, as an
      outpatient procedure, has been found to be simple and useful in the patients of
      sciatica with prolapsed lumbar intervertebral disc potentially appropriate for a
      low-resource setting.

PMID- 16105350
TI  - Ectopic pregnancy: an 11-year review in a tertiary centre in the Niger Delta.
AB  - Ectopic pregnancy still remains a leading cause of maternal mortality and
      morbidity in the first trimester of pregnancy and also a significant cause of
      reproductive failure in Nigeria. A descriptive review of 211 consecutive cases of
      ectopic gestation over an 11-year period was undertaken. Ectopic pregnancy
      constituted 9.5% of gynaecological admissions. In all, 86% were nulliparous and
      62.6% were married. Abdominal pain and tenderness were the most consistent modes
      of presentation. Also, 95.3% presented as ruptured ectopic pregnancy. Induced
      abortion (72%) was the most common factor associated with ectopic pregnancy.
      Anaemia was the most common post-operative complication. In all, 21% had prior
      dilatation and curettage as a result of misdiagnoses. The case fatality rate was
      2.5%. Ectopic pregnancy presents a major public health challenge among women of
      reproductive age in this region. Community-based comprehensive health education
      programme focusing on contraception, sex education, prevention and treatment of
      postabortal sepsis, pelvic inflammatory disease and puerperal sepsis are urgently
      needed.

PMID- 16105351
TI  - Bowel prolapse and gangrene following vaginal vault perforation: an example of
      the menace of criminal abortion in Nigeria.

PMID- 16105352
TI  - Mortality of tetanus at the Lagos University Teaching Hospital, Nigeria.
AB  - Records of 349 tetanus patients, aged 10 years and above, admitted to the Lagos
      University Teaching Hospital, Nigeria, between 1990 and 1999 were reviewed. The
      male:female ratio was 1.98:1, and the ages were between 10 and 88 years, with a
      mean age of 29.8 years. The overall case fatality rate (CFR) of tetanus was
      36.96% (33.19% for men and 44.44% for women). The CFR is similar to that
      previously reported in the hospital, but higher than that reported from Europe
      and North America. The lowest CFR was in the 10-19-year age group, and there was
      a trend towards increasing CFR with increasing age. Tetanus patients in the
      intensive care unit (ICU) had a significantly higher CFR than those in the
      medical wards. Unlike in developed countries, where management of tetanus in ICU
      has resulted in a decrease in CFR, the CFR of tetanus at the Lagos University
      Teaching Hospital has not significantly reduced over the years.

PMID- 16105353
TI  - Crusted papule on forehead due to Dirofilaria repens.

PMID- 16105354
TI  - Lateral sinus thrombosis in neurocysticercosis.
AB  - Cysticercosis is a frequent parasitic infection in developing countries including
      Nepal and is related to poverty, ignorance and pig-rearing practices at home in
      the community. A variety of structural involvements such as brain parenchyma,
      cerebellum, ventricular system, brain stem, meninges, subarachnoid space, spinal
      cord and orbit have been reported, but cysticercus involving the lateral sinus
      causing thrombosis is extremely rare.

PMID- 16105355
TI  - Tuberculous meningitis in Turkish children: an evaluation of 38 cases.
AB  - Thirty-eight cases of tuberculous meningitis in children were studied. Mortality
      was 28.9%; most of these presented with stage III disease. Tuberculous meningitis
      (TBM) still ranks as one of the most important communicable diseases in terms of
      morbidity and mortality. It is universally fatal if not treated and has high
      morbidity and mortality, if not recognized early. According to WHO's data, 1.3
      million new TB cases under 15 year olds were reported. In Turkey, the TB
      prevalence is 0.4 %. According to data from the Turkish Ministry of Health, the
      number of admissions to hospitals dropped from 108 per 100,000 in 1971 to 51 per
      10,000 in 1988. Early diagnosis and treatment of TBM are essential in order to
      prevent late sequelas and death. The diagnosis of TBM may be delayed because many
      patients initially have vague, seemingly minor, signs and symptoms. In this
      study, the clinical and laboratory findings of 38 patients with the diagnosis of
      TBM in our hospital were reviewed, retrospectively, during the past five years.
      Our purpose was to stress the importance of TBM as a public health problem in
      Turkey, particularly in the Eastern of Turkey.

PMID- 16105356
TI  - Near fatal respiratory obstruction due to Ascaris lumbricoides.

PMID- 16105357
TI  - Primary amenorrhoea: three cases from a semi-rural Namibian hospital.
AB  - We discuss the diagnostic process of three patients presenting with primary
      amenorrhoea in Onandjokwe Lutheran Hospital in Northern Namibia. This semirural
      district hospital also serves as a referral hospital and has both ultrasound and
      laparoscopy possibilities.

PMID- 16105358
TI  - A new focus for cutaneous leishmaniasis in the West Coast of Turkey.

PMID- 16105359
TI  - Guardians' attitudes to children with physical disabilities in Malawi.

PMID- 16105360
TI  - Paratyphoid fever in Vellore, South India.

PMID- 16105361
TI  - Prevalence of hepatitis B virus infection in young Turkish men.

PMID- 16105363
TI  - Preventing accidental injuries in children: champions needed in primary care.

PMID- 16105364
TI  - NICE suspected cancer guidelines.

PMID- 16105365
TI  - Promoting child safety in primary care: a cluster randomised controlled trial to
      reduce baby walker use.
AB  - BACKGROUND: Baby walkers are commonly used items of nursery equipment, but cause
      more than 3000 injuries each year in the UK. There is currently little evidence
      regarding the effectiveness of interventions in primary care to reduce walker
      use. AIM: To evaluate the effectiveness of an educational package provided by
      midwives and health visitors to reduce baby walker possession and use. DESIGN OF
      STUDY: Cluster randomised controlled trial. SETTING: Sixty-four general practices
      in Nottingham and North Nottinghamshire, UK. METHOD: An educational package aimed
      at discouraging mothers-to-be from obtaining and using a walker was delivered by
      midwives and health visitors to 1174 mothers-to-be of at least 28 weeks
      gestation. The control arm received usual care. Primary outcome measures were the
      possession and use of a walker. Secondary outcome measures included the frequency
      and duration of walker use, knowledge and attitudes towards walkers, plans to use
      a walker with future children, recommending a walker to a friend, and use of
      stair gates and fire guards. RESULTS: Intervention arm participants were
      significantly less likely to own (odds ratio [OR] = 0.63, 95% confidence interval
      [CI] = 0.43 to 0.93) or to use a walker (OR = 0.26, 95% CI = 0.08 to 0.84). They
      were significantly less likely to plan to use a walker with their next child (OR
      = 0.52, 95% CI = 0.31 to 0.86) or to agree that walkers keep children safe (OR =
      0.35, 95% CI = 0.16 to 0.78). There was some evidence that they were less likely
      to recommend a walker to a friend (OR = 0.51, 95% CI = 0.28 to 0.91) or to agree
      that they help children to walk more quickly (OR = 0.53, 95% CI = 0.29 to 0.95).
      CONCLUSION: An educational package delivered by midwives and health visitors was
      effective in reducing baby walker possession and use. Providers of primary
      healthcare services should include baby walker education in their injury
      prevention strategy and child health promotion programme.

PMID- 16105366
TI  - Recent changes in the prevalence of diseases presenting for health care.
AB  - BACKGROUND: Practice-based morbidity surveys inform on the prevalence of diseases
      presenting for health care. The last major survey in England and Wales was
      conducted in 1991. AIM: To reveal changes in disease prevalence between 1991 and
      2001. DESIGN OF STUDY: Population-based analysis of persons presenting to GPs.
      Annual prevalence of diseases reported in the Weekly Returns Service (WRS) of the
      Royal College of General Practitioners in 2001 was compared with prevalence
      reported in Morbidity Statistics from General Practice, Fourth National Study
      (MSGP4). SETTING: Thirty-eight general practices contributing to the WRS,
      monitoring a population of 326,000 in 2001. METHOD: Prevalence was determined
      from Read codes for morbidity entered in the respective survey years. Diseases
      and disease groups were defined from Read codes mapping to the chapters, major
      sub-groups and 3-digit codes of the International Classification of Disease
      version 9 (ICD9). Age-standardised prevalence rates per 10,000 registered persons
      and 99% confidence intervals (CIs) were calculated using the national census
      population for 2001 as the standard. Survey differences in prevalence were
      identified from non-overlapping CIs. RESULTS: There was a general reduction in
      the prevalence of disease caused by infection and an increase of degenerative
      disorders. The prevalence of mental disorders, skin disease and musculoskeletal
      disorders showed little change. Particular increases were noted for other
      malignant and benign neoplasms of the skin, hypothyroidism and diabetes. There
      were marked reductions for disorders of the conjunctiva, ear infections, acute
      myocardial infarction and heart failure, respiratory infections and injuries.
      CONCLUSIONS: The role of the GP continues to change. These results confirm the
      importance of the management of chronic diseases as the dominant (though not the
      sole) role of the GP. The results demonstrate the use of the WRS as a source of
      data on disease prevalence.

PMID- 16105367
TI  - Temporal change in the prevalence of respiratory symptoms and obstructive airways
      disease 1993-2001.
AB  - BACKGROUND: There has been little available information regarding secular changes
      in the prevalence of respiratory symptoms since the mid-1990s. AIM: To examine
      changes in the prevalence of respiratory symptoms for 1993-2001. DESIGN OF STUDY:
      A series of postal questionnaire surveys. SETTING: Two general practice
      populations, including all age groups. METHOD: Four postal respiratory
      questionnaire surveys were conducted between 1993 and 2001. Subjects who replied
      to two or more surveys (8058 adults and 2350 children) were included in the main
      analyses. Validated scoring systems were used to define obstructive airways
      disease in adults and asthma in children. RESULTS: Over the 8-year observation
      period there were increases among adults in the crude prevalence of wheeze, being
      woken by cough, receipt of current asthma medication, and of obstructive airways
      disease, compared with decreases in children for wheeze, night cough, asthma
      attacks, and asthma. For adults, adjusted odds ratios per year of secular
      increase were 1.03 (95% confidence interval [CI] = 1.02 to 1.03) for wheeze, 1.03
      (95% CI = 1.02 to 1.03) for being woken by cough, 1.03 (95% CI = 1.02 to 1.04)
      for asthma medication, and 1.02 (95% CI = 1.01 to 1.03) for obstructive airways
      disease. These increases were greater in those aged over 44 years, in males, and
      in those without a family history of asthma or a history of hayfever or eczema.
      Corresponding decreases for children were 0.94 (95% CI = 0.92 to 0.97) for
      wheeze, 0.93 (95% CI = 0.91 to 0.96) for night cough, 0.93 (95% CI = 0.90 to
      0.95) for asthma attacks and 0.98 (95% CI = 0.95 to 1.00) for asthma. CONCLUSION:
      The increases found in adults are more likely to be due to chronic obstructive
      pulmonary disease (COPD) than asthma. This is supported by the decreases in
      symptom and asthma prevalence in children.

PMID- 16105368
TI  - Variations in antibiotic prescribing and consultation rates for acute respiratory
      infection in UK general practices 1995-2000.
AB  - BACKGROUND: Antibiotic prescribing by GPs in the UK has declined since 1995. AIM:
      We investigated whether general practices that issue fewer antibiotic
      prescriptions to patients presenting with acute respiratory infections had lower
      consultation rates for these conditions. DESIGN OF STUDY: Retrospective data
      analysis. SETTING: UK general practice. METHOD: We analysed data from the General
      Practice Research Database, including all registered patients from 108 practices
      between 1995 and 2000. For each practice, numbers of consultations for acute
      respiratory tract infections and the proportion of consultations resulting in an
      antibiotic prescription were obtained. An age- and sex-standardised consultation
      ratio (SCR) and standardised prescription ratio (SPR) were calculated for each
      practice. We evaluated whether SPR and SCR values were associated. RESULTS: For
      the mid-year data (1997), the crude consultation rate for all acute respiratory
      infections ranged from 125-1,110 per 1,000 registered patients at different
      practices; the proportion of consultations with antibiotics prescribed ranged
      from 45-98%. After standardising for varying age and sex structure of practice
      populations, practices with lower SPR values had lower SCR values (r = 0.41;
      P<0.001). This association was observed in each study year. Moreover, practices
      that demonstrated reductions in SPR between 1995 and 2000 also showed reductions
      in SCR (r = 0.27; P = 0.005). CONCLUSION: Practices that prescribe antibiotics to
      a smaller proportion of patients presenting with acute respiratory infections
      have lower consultation rates for these conditions. Practices that succeed, over
      time, in reducing antibiotic prescribing also experience reductions in
      consultation rates for these conditions. Although our methodology cannot prove
      that these two findings are causally related, they imply that patients alter
      their illness behaviour and that this may be a response to previous consultation
      experience. In consequence, respiratory illness in the community may be
      undergoing a process of de-medicalisation.

PMID- 16105369
TI  - The workload of GPs: consultations of patients with psychological and somatic
      problems compared.
AB  - BACKGROUND: GPs report that patients' psychosocial problems play a part in 20% of
      all consultations. GPs state that these consultations are more time-consuming and
      the perceived burden on the GP is higher. AIM: To investigate whether GPs'
      workload in consultations is related to psychological or social problems of
      patients. DESIGN OF STUDY: A cross-sectional national survey in general practice,
      conducted in the Netherlands from 2000-2002. SETTING: One hundred and four
      general practices in the Netherlands. METHOD: Videotaped consultations (n = 1392)
      of a representative sample of 142 GPs were used. Consultations were categorised
      in three groups: consultations with a diagnosis in the International
      Classification of Primary Care chapter P 'psychological' or Z 'social' (n = 138),
      a somatic diagnosis but with a psychological background according to the GP (n =
      309), or a somatic diagnosis and background (n = 945). Workload measures were
      consultation length, number of diagnoses and GPs' assessment of sufficiency of
      patient time. RESULTS: Consultations in which patients' mental health problems
      play a part (as a diagnosis or in the background) take more time and involve more
      diagnoses, and the GP is more heavily burdened with feelings of insufficiency of
      patient time. In consultations with a somatic diagnosis but psychological
      background, GPs more often experienced a lack of time compared to consultations
      with a psychological or social diagnosis. CONCLUSION: Consultations in which the
      GP notices psychosocial problems make heavier demands on the GP's workload than
      other consultations. Patients' somatic problems that have a psychological
      background induce the highest perceived burden on the GP.

PMID- 16105370
TI  - Clinical symptoms and signs in sore throat patients with large colony variant
      beta-haemolytic streptococci groups C or G versus group A.
AB  - BACKGROUND: The role of large colony streptococci groups C or G as pathogen
      agents in sore throat has been questioned. AIM: To analyse clinical features of
      patients with large colony streptococci groups C or G compared with patients with
      group A streptococci (GAS) and with negative cultures. DESIGN OF STUDY:
      Prospective study of patients with sore throat. SETTING: Two Norwegian general
      practices in Stokke and Kongsberg communities with 6500 patients. METHOD:
      Frequency of clinical features in the three patient categories including the four
      Centor criteria (fever, anterior cervical lymphadenopathy, tonsillar exudates,
      and lack of cough), degree of pain on swallowing, pharyngeal rubor, C-reactive
      protein (CRP) values, patient age between 3 and 14 years, and duration of
      symptoms before seeing the doctor. A logistic regression analysis to find
      independent predictors was performed. RESULTS: Out of 306 patients with a sore
      throat, 244 were adults and 62 were children under 10 years old; 40% were men.
      One hundred and twenty-seven had GAS, 33 had streptococci groups C or G, and 146
      had negative throat cultures. Forty-eight per cent of the GAS patients and 45% of
      the C or G patients met three or four of the Centor criteria. The logistic
      regression revealed that in patients with GAS considerable pain on swallowing, an
      age of 3-14 years and a duration of symptoms of < or =3 days or less were
      significantly associated with GAS infection in addition to the Centor criteria.
      The same results were found when all streptococci were analysed together, in
      addition elevated CRP was significant. In patients with streptococci group C or G
      an elevated CRP-value was significantly associated. CONCLUSION: Patients with
      tonsillitis caused by streptococcus groups C or G have, to a large extent, the
      same clinical picture as patients with GAS. Large colony streptococci groups C
      and G should be considered as throat pathogens in line with GAS.

PMID- 16105371
TI  - Ethical principles and the rationing of health care: a qualitative study in
      general practice.
AB  - BACKGROUND: Researching sensitive topics, such as the rationing of treatments and
      denial of care, raises a number of ethical and methodological problems. AIM: To
      describe the methods and findings from a number of focus group discussions that
      examined how GPs apply ethical principles when allocating scarce resources.
      DESIGN OF STUDY: A small-scale qualitative study involving purposive sampling,
      semi-structured interviews and focus groups. SETTING: Twenty-four GPs from two
      contrasting areas of London: one relatively affluent and one relatively deprived.
      METHOD: Initial interviews asked GPs to identify key resource allocation issues.
      The interviews were transcribed and themes were identified. A number of case
      studies, each illustrative of an ethical issue related to rationing, were written
      up in the form of vignettes. In focus group discussions, GPs were given a number
      of these vignettes to debate. RESULTS: With respect to the ethical basis for
      decision making, the findings from this part of the study emphasised the role of
      social and psychological factors, the influence of the quality of the
      relationship between GPs and patients and confusion among GPs about their role in
      decision making. CONCLUSION: The use of vignettes developed from prior interviews
      with GPs creates a non-threatening environment to discuss sensitive or
      controversial issues. The acceptance by GPs of general moral principles does not
      entail clarity of coherence of the application of these principles in practice.

PMID- 16105372
TI  - A qualitative study to investigate why patients accept or decline a copy of their
      referral letter from their GP.
AB  - BACKGROUND: Our practice in Northumberland has offered patients copies of their
      clinical referral letters for almost 3 years. However, many patients declined
      this offer and this qualitative study was conducted to determine why almost 80%
      of patients offered a copy of their referral letter opted not to receive one.
      AIM: To discover why some patients accepted and others declined a copy of the
      letter written from GP to specialist. DESIGN OF STUDY: A qualitative focus-group
      study. SETTING: General practice in Northumberland. METHOD: Three focus groups of
      referred patients were created, and discussions were taped, transcribed and
      analysed for major themes. RESULTS: The patients chose to accept or decline a
      copy of their referral letter for diverse reasons. However, most felt that the
      ability to choose for themselves whether to have a copy or not was essential.
      CONCLUSIONS: The concept of trust in their GP was a major theme that patients
      related was often behind their decision to decline a copy of their letter. These
      results, if transferable, may have implications for the application of this
      policy.

PMID- 16105373
TI  - Epidemiology of unintentional injuries in childhood: a population-based survey in
      general practice.
AB  - This study aimed to assess the incidence of unintentional injuries presented in
      general practice, and to identify children at risk from experiencing an
      unintentional injury. We used the data of all 0-17-year-old children from a
      representative survey in 96 Dutch general practices in 2001. We computed
      incidence rates and multilevel multivariate regression analysis in different age
      strata and identified patient and family characteristics associated with an
      elevated injury risk. Nine thousand four hundred and eighty-four new injury
      episodes were identified from 105 353 new health problems presented in general
      practice, giving an overall incidence rate of 115 per 1000 person years (95%
      confidence interval [CI] = 113 to 118). Sex and residence in rural areas are
      strong predictors of injury in all age strata. Also, in children aged 0-4 years,
      a higher number of siblings is associated with elevated injury risk (> or =3
      siblings odds ratio [OR] = 1.57, 95% CI = 1.19 to 2.08) and in the 12-17-year
      olds, ethnic background and socioeconomic class are associated with experiencing
      an injury (non-western children OR = 0.67, 95% CI = 0.54 to 0.81; low
      socioeconomic class OR = 1.39, 95% CI = 1.22 to 1.58). Unintentional injury is a
      significant health problem in children in general practice, accounting for 9% of
      all new health problems in children. In all age groups, boys in rural areas are
      especially at risk to experience an injury.

PMID- 16105374
TI  - The challenge of recruiting people with schizophrenia to a health promotion
      trial.
AB  - People with schizophrenia have an increased risk of coronary heart disease. This
      pilot study tested the feasibility of carrying out a randomised controlled trial
      to compare coronary heart disease prevention for this population through an
      enhanced occupational therapy support intervention versus a practice-based
      intervention. Difficulty in deciding whether to take part meant that 123 visits
      were made to 25 people with 12 ultimately providing informed consent.
      Participants' discussion at a subsequent focus group (n = 3) suggested a poor
      understanding of the study process. Distrust of randomisation suggests that
      randomised controlled trials may not be the best way to evaluate community-based
      interventions for people with schizophrenia.

PMID- 16105375
TI  - Random drug testing in schools.

PMID- 16105376
TI  - Homeopathy.

PMID- 16105377
TI  - Prescribing to substance misusers.

PMID- 16105378
TI  - When the drugs don't work.

PMID- 16105379
TI  - Mechanisms of revalidation.

PMID- 16105397
TI  - The origin of the word "bari".
AB  - Our field is "bariatric" surgery. Bari means weight or pressure in ancient and
      modern Greek. However, bari denotes obese in biblical Hebrew and healthy in
      modern Hebrew. The Greek language and the Hebrew language (spoken by many ancient
      Northwest Semitic peoples) come from different language roots. We surveyed
      interactions between the two languages, to determine historically how bari could
      have become a "loanword". Ample mingling of the peoples was found.

PMID- 16105398
TI  - Current indications for preoperative inferior vena cava filter insertion in
      patients undergoing surgery for morbid obesity.
AB  - BACKGROUND: Pulmonary embolus is a potentially lethal complication in patients
      undergoing surgery for morbid obesity. In a select group of patients at high risk
      for venous thromboembolic events (VTE), we have chosen to prophylactically insert
      inferior vena cava filters via a jugular percutaneous approach. We propose
      guidelines for preoperative insertion of inferior vena cava filters in patients
      with clinically significant obesity. METHODS: All patients who underwent
      preoperative insertion of inferior vena cava (IVC) filters as prophylaxis for
      pulmonary emboli were reviewed. Data regarding body mass index (BMI), prior
      history of venous thromboembolism, current anticoagulant usage, as well as other
      patient data were compiled and analyzed. Additionally, all operative notes were
      reviewed, and operative data were analyzed and compared. RESULTS: 14 patients
      underwent preoperative IVC filter placement before gastric bypass. Mean patient
      age was 49.1 +/- 1.52 years and mean BMI was 56.5 +/- 4.45 kg/m2. No
      complications occurred due to preoperative filter placement, and no pulmonary
      emboli occurred in this group. Indications for preoperative IVC filter insertion
      included prior pulmonary embolus (6), prior deep venous thrombosis (7), and lower
      extremity venous stasis (1). CONCLUSIONS: Vena caval filter placement in the
      preoperative period can be undertaken safely in bariatric patients. We recommend
      that routine preoperative vena caval filter placement should be undertaken in all
      bariatric patients with prior pulmonary embolus, prior deep venous thrombosis,
      evidence of venous stasis, or known hypercoagulable state. Possible roles for IVC
      filter placement in this patient population are expanding as more data is
      acquired.

PMID- 16105399
TI  - Postural changes in morbidly obese patients.
AB  - BACKGROUND: Postural deviations in morbidly obese individuals may contribute to
      low self-esteem and to long-term adverse effects on bones and joints. In a case
      control study, the axial skeleton was investigated, to disclose the main
      abnormalities found in obese compared to non-obese groups. METHODS: 2 groups were
      compared. Group 1, severely obese patients (n= 32), age 41.5 +/- 8.2 years, BMI
      49.4 +/- 6.6 kg/m2, 93.8% females, and group 2 non-obese (n= 30), age 43.5 +/-
      5.8 years, BMI 24.6 +/- 5.1 kg/m2, 96.7% females, had their posture analyzed
      through clinical examination and radiological imaging. Variables measured were
      anterior, lateral and posterior angular deviation from the vertical body axis at
      the head, shoulders, pelvis, Thales triangle, spine, knees, ankles and feet. Data
      are shown as a percentage of abnormal angles in the 2 groups. RESULTS: On
      anterior analysis of the 2 groups, disturbances affected head (37.5% vs 13.3%),
      Thales angle (78.1% vs 53.3%), knees (84.4% vs 33.3%), legs (59.4% vs 30.0%) and
      support base (59.4% vs 26.7%) (P<0.05). On posterior view, the spine was the
      deranged segment (87.5% vs 36.7%) (P<0.05), and on lateral assessment, 100% of
      the results were abnormal. CONCLUSIONS: 1) Individuals with morbid obesity
      present important postural alterations. 2) Seriously altered posture was the rule
      for the obese population in this study, especially in the spine, knees and feet.
      3) Most patients had compatible clinical complaints, but they rarely associated
      the bone and joint pain with the obesity and axial skeleton deviations. 4)
      Planned physical activity should be part of the treatment of severe obesity, in
      order to correct deviations, prevent new ones, and improve quality of life.

PMID- 16105400
TI  - Pre- and post-prandial plasma ghrelin levels do not correlate with satiety or
      failure to achieve a successful outcome after Roux-en-Y gastric bypass.
AB  - BACKGROUND: We tested the hypothesis that the amount of weight lost after Roux-en
      Y gastric bypass (RYGBP) correlates with plasma ghrelin levels. METHODS: 36
      morbidly obese patients were studied 3 years after RYGBP (6 men, 30 women) with
      mean initial BMI 51 kg/m2 and 8 healthy controls (2 men, 6 women) with mean BMI
      25 kg/m2. Subjects consumed a light breakfast, and the first blood sample was
      drawn at 1200 hrs immediately before lunch and the second sample at 1400 hrs.
      Satiety was assessed using a Visual Analog Scale (VAS). Patients were stratified
      as success (current BMI <35) or failures (current BMI > or =35). RESULTS: Plasma
      ghrelin levels were significantly lower in patients after RYGBP (269 +/- 66
      pcg/ml) compared with lean controls (616 +/- 112 pcg/ml, P<0.001). Ghrelin levels
      pre or post meals were not different between patients who had a successful weight
      loss (preoperative BMI 47, current BMI 29, 72% EWL) or those who achieved a less
      then ideal weight loss (preoperative BMI 48, current BMI 41, 29% EWL). There was
      no correlation between any of the VAS scores and plasma ghrelin. There was a
      strong inverse correlation between pre-prandial ghrelin levels and the
      preoperative or current BMI. CONCLUSION: Failure to lose weight after RYGBP does
      not correlate with pre- or post-prandial ghrelin plasma levels. Ghrelin levels
      were inversely proportional to BMI and did not correlate with satiety. These data
      do not support a role for higher plasma ghrelin levels for inadequate weight loss
      after RYGBP.

PMID- 16105401
TI  - Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels.
AB  - BACKGROUND: Different changes of plasma ghrelin levels have been reported
      following gastric banding, Roux-en-Y gastric bypass, and biliopancreatic
      diversion. METHODS: This prospective study compares plasma ghrelin levels and
      weight loss following laparoscopic sleeve gastrectomy (LSG) and laparoscopic
      adjustable gastric banding (LAGB) in 20 patients. RESULTS: Patients who underwent
      LSG (n=10) showed a significant decrease of plasma ghrelin at day 1 compared to
      preoperative values (35.8 +/- 12.3 fmol/ml vs 109.6 +/- 32.6 fmol/ml, P=0.005).
      Plasma ghrelin remained low and stable at 1 and 6 months postoperatively. In
      contrast, no change of plasma ghrelin at day 1 (71.8 +/- 35.3 fmol/ml vs 73.7 +/-
      24.8 fmol/ml, P=0.441) was found in patients after LAGB (n=10). Increased plasma
      ghrelin levels compared with the preoperative levels at 1 (101.9 +/- 30.3 fmol/ml
      vs 73.7 +/- 24.8 fmol/ml, P=0.028) and 6 months (104.9 +/- 51.1 fmol/ml vs 73.7
      +/- 24.8 fmol/ml, P=0.012) after surgery were observed. Mean excess weight loss
      was higher in the LSG group at 1 (30 +/- 13% vs 17 +/- 7%, P=0.005) and 6 months
      (61 +/- 16% vs 29 +/- 11%, P=0.001) compared with the LAGB group. CONCLUSIONS: As
      a consequence of resection of the gastric fundus, the predominant area of human
      ghrelin production, ghrelin is significantly reduced after LSG but not after
      LAGB. This reduction remains stable at follow-up 6 months postoperatively, which
      may contribute to the superior weight loss when compared with LAGB.

PMID- 16105402
TI  - Laparoscopic sleeve gastrectomy as an initial bariatric operation for high-risk
      patients: initial results in 10 patients.
AB  - BACKGROUND: The outcomes and initial results of laparoscopic sleeve gastrectomy
      were evaluated. METHODS: A prospective study of the initial 10 patients who
      underwent laparoscopic sleeve gastrectomy (LSG) was performed. Study endpoints
      included operative time, complication rates, hospital length of stay and
      percentage of excess weight loss (%EWL). RESULTS: There were 5 women and 5 men,
      with mean age 43 years (range 31 to 52). Mean preoperative weight was 182 kg
      (range 125-247 kg), with mean preoperative BMI 64 (range 61-80). Indication for
      LSG was related to BMI in all patients. 1 patient had previous restrictive
      bariatric surgery. Mean operative time was 2 hours (range 1.5-2.5). No patient
      required conversion. There were no postoperative complications nor mortality.
      Median hospital stay was 7.2 days. Average %EWL and BMI at 1 year were 51% and 23
      kg/m2, respectively. CONCLUSION: LSG can be safely integrated into a bariatric
      surgical program with good results in terms of weight loss and quality of life.
      LSG can be a firststage procedure before gastric bypass or duodenal switch or a
      one-stage restrictive procedure if longterm results are good. LSG should be
      considered as a surgical option in the bariatric field.

PMID- 16105403
TI  - Minimal reporting requirements for weight loss: current methods not ideal.
AB  - BACKGROUND: There is variety in the reporting of weight loss outcomes within the
      bariatric literature. Our aim is to compare methods of reporting weight loss in
      surgical and medical studies, and in addition look for a minimal reporting
      requirement that allows meaningful comparison. METHOD: A review of methods of
      reporting weight loss in studies published during 2004 was conducted. Bariatric
      surgical studies included all reports from MEDLINE-listed journals, and medical
      studies included reports of non-surgical weight loss from 9 leading journals.
      RESULTS: 65 surgical and 36 non-surgical reports were retrieved. There were 3
      common (>20% of reports) methods of reporting in the surgical literature; mean
      weight, percentage of excess weight loss (%EWL) and body mass index (BMI), and 4
      in the medical literature; mean weight loss, weight, percentage weight loss and
      BMI. %EWL was reported in 2/3 of surgical reports and in none of the non
      surgical. The origin of ideal weight for %EWL calculations was reported in 10
      (23%) of these studies and included 5 differing definitions. All methods of
      reporting other than those using "ideal weight" can be calculated from mean
      weight and BMI at all time-points. CONCLUSION: There is complexity and confusion
      in the reporting of bariatric surgery weight outcomes when calculations are based
      on ideal weight. Providing weight (kg) and BMI (kg/m2) at all time-points allows
      the reader to interpret and compare the results in the context of the population
      of interest. These two measures should be provided as a minimum by all journals
      reporting on intentional weight loss.

PMID- 16105404
TI  - Minimal reporting requirements for weight loss.

PMID- 16105405
TI  - Adjustable gastric banding in an ambulatory surgery center.
AB  - BACKGROUND: We report our early experience with 343 consecutive patients who
      underwent laparoscopic adjustable gastric banding (LAGB) as an outpatient
      procedure in a self-standing ambulatory surgery center. METHODS: Between Apr 2003
      and Feb 2005, data was collected prospectively on 343 consecutive patients who
      underwent LAGB as an outpatient. RESULTS: There were 305 females (88.9%) and 38
      males (11.1%), with mean age 43.5 years (+/-SD 9.9, range 19-67) and mean BMI
      44.5 kg/m2 (+/-SD 6.1, range 32.7-62.7). Mean operating-room time was 52.9 (+/
      16.3) minutes. 10 complications occurred in 9 patients (2.8%): 5 stoma occlusion,
      3 port problems requiring port replacement, 1 superficial wound infection, and 1
      colon perforation associated with adhesiolysis requiring band removal. 3 patients
      required admission to the hospital: 1 for nausea, 1 for observation after bloody
      nasogastric tube drainage, and 1 for dysphagia due to esophageal spasm. All 9
      patients with complications recovered fully. 1-year weight loss data was
      available in 91 patients; mean percent excess weight lost (%EWL) at 1 year was
      45.4% (+/-17.6). CONCLUSIONS: LAGB has become an appropriate outpatient procedure
      in select patients.

PMID- 16105406
TI  - Reduction in slippage with 11-cm Lap-Band and change of gastric banding
      technique.
AB  - BACKGROUND: Slippage occurs after 2-18% of gastric bandings performed by the
      perigastric technique (PGT). We investigated the slippage-rate before and after
      the introduction of the pars flaccida technique (PFT) and the 11-cm Lap-Band, and
      the long-term results of the re-operated patients. METHODS: Between Dec 1996 and
      Feb 2004, 360 patients with a mean BMI of 44 kg/m2 were operated. The PGT (n=168)
      and PFT9.75 (n=15) groups received the 9.75-cm Lap-Band, and the PFT11 group
      (n=177) received the new 11-cm Lap-Band. Follow-up rate was 99%. RESULTS:
      Slippage occurred in a total of 31 patients from all groups (PGT, n=28, or 17%;
      PFT9.75, n=1, or 7%; PFT11, n=2, or 1%). Average yearly re-operation rate for
      slippage in the first 3 years postoperatively was 3.8%, 2.2% and 0.9%,
      respectively. Laparoscopic re-banding was necessary for posterior (n=19) or
      lateral (n=12) slippage. The late postoperative course after re-banding was:
      uneventful 58%, weight regain 35% and/or esophageal motility disorder 23%,
      secondary band intolerance 20%, and one persistent posterior slippage. 8 patients
      (26%) needed biliopancreatic diversion. CONCLUSION: Since the introduction of the
      PFT and the 11-cm Lap-Band, we observed a significant reduction in slippage rate
      and no posterior slippage. Re-banding had a less favorable long-term result than
      did first-procedure banding.

PMID- 16105407
TI  - Endothelial function and weight loss in obese humans.
AB  - BACKGROUND: Obesity is a major risk factor for the development of endothelial
      dysfunction. We explored the effect of different degrees of body mass on
      endothelial function, lipids, systemic inflammation and glucose homeostasis and
      the effect of surgically-induced weight loss on endothelial function in severely
      obese humans. METHODS: A cross-sectional study of healthy subjects across a wide
      range of body fatness was performed to characterize the effect of obesity on flow
      mediated dilatation (FMD), systemic inflammation, blood pressure and insulin
      sensitivity. A longitudinal study was performed to assess the effect of bariatric
      surgery induced weight loss on these parameters. 73 healthy subjects across a
      wide range of body mass were recruited; of these, 8 underwent bariatric surgery
      (median BMI 52.2 kg/m2, interquartile range 50.355.9). Endothelial dependent
      vasodilatation was measured using the brachial artery vasodilatory response to
      forearm hyperemia assessed using highresolution ultrasonography. RESULTS: Obese
      subjects were characterised by a complex collection of abnormalities, with
      hypertension, impaired glucose homeostasis, systemic inflammation and reduced
      FMD. BMI < or =25 kg/m2 (median FMD 9.7%, interquartile range 6.8-12.2), BMI >30
      kg/m2 (median FMD 6.7% 4.8-7.5), P=0.01 comparing FMD in lean and obese subjects.
      A mean reduction in weight of 23.4 (4.6) kg produced an improvement in FMD from
      5.3% (3.87.0) to 10.2% (7.6-13.3), P=0.01. CONCLUSIONS: Even moderate obesity
      leads to endothelial dysfunction. In severely obese subjects, FMD is normalized
      by weight loss. This improvement in FMD is associated with a decline in
      inflammatory markers, blood pressure and insulin. The improvement in FMD occurred
      despite patients remaining significantly obese. These results suggest that an
      integrated approach to improving endothelial function in obese humans may be
      necessary.

PMID- 16105408
TI  - Comparative analysis of vertical banded gastroplasty and duodenal switch at five
      years follow-up.
AB  - BACKGROUND: Bariatric surgery is the only effective long-term treatment for
      morbid obesity. We compared long-term results of the vertical banded gastroplasty
      (VBG) and biliopancreatic diversion with duodenal switch (DS). Quality of life
      (QoL), weight loss (WL), and reoperation were evaluated. METHODS: This is a
      retrospective study of 85 of 129 patients with VBG and 49 of 743 patients with
      DS, with follow-up >5 years. Mean preoperative BMI of the VBG patients was 48.8
      kg/m2 and for the DS patients was 50.3 kg/m2. RESULTS: Percent excess weight loss
      (%EWL) at 5 years for VBG patients was 56.4% and for DS patients 70.6%
      (P<0.0001). 8 VBG patients (9.4%) and 1 DS patient (2.0%) required re-operation
      due to failure of the technique. None of the VBG patients could eat a normal
      diet, while 80% of the DS had no restriction in the quality of their intake.
      CONCLUSIONS: At 60 months follow-up, only the DS patients fullfilled the ASBS
      requirements of %EWL >50 in over 75% of the patients.

PMID- 16105409
TI  - Patients postoperatively forget aspects of preoperative patient education.
AB  - BACKGROUND: Preoperative patient education is critically important to the success
      of any bariatric operation. In our clinic, we perform extensive preoperative
      education and informed consent. Part of the informed consent process includes a
      preoperative true/false quiz. This study tests the hypothesis that postoperative
      patients do not recall key components of their preoperative education. METHODS:
      Preoperatively, all patients were required to take the true/false quiz and retake
      it, if necessary, until they received all the questions correct. All patients
      were given their preoperative informed consent quiz again at least 1 month after
      laparoscopic gastric bypass, during their postoperative clinic visit. Patients >1
      year postoperatively from surgery were compared to patients <1 year
      postoperatively. RESULTS: 63 patients were included in this study. Originally,
      46% of patients did not get all the questions correct the first time; mean score
      on the quiz preoperatively was 95%. Patients took the test an average of 8 months
      after surgery. Postoperatively, 46% of patients did not get all the questions
      correct; mean score on the quiz was 96%. The 2 most common incorrect answers
      were: "Obesity surgery is basically an aid to dieting: it does not mean that you
      will lose weight no matter what you eat or do (True)" and "Diabetes, high blood
      pressure, back pain and similar ailments always get better after obesity surgery
      (False)". Patients >1 year postoperative were more likely not to get all the
      questions correct (80% vs 36%; P<0.01; two-tailed Fisher's exact test).
      CONCLUSIONS: Patients do not remember basic preoperative education facts after
      their bariatric surgery. Despite maximal efforts in verifying preoperative
      education, patients often forget this critical information after bariatric
      surgery. Patients 1 year after surgery forget more information.

PMID- 16105410
TI  - Health-related quality of life in patients with class II and class III obesity.
AB  - BACKGROUND: Severe obesity may substantially impact quality of life. We estimated
      the health-related quality of life (HRQoL) in patients with class II and class
      III obesity, and explored the impact of patient characteristics and co
      morbidities on quality of life. METHODS: 110 patients with BMI > or = 35 kg/m2
      presenting for evaluation for bariatric surgery were asked to complete the
      EuroQoL questionnaire. Co-morbidities of the patients were recorded, including
      coxarthralgia, gonarthralgia, foot problems (pain and arthrosis), diabetes,
      dyslipidemia, hypertension, infertility, coronary heart disease, low back pain,
      peptic esophagitis, sleep apnea syndrome, urinary stress incontinence, and venous
      insufficiency. The determinants of HRQoL on the EQ-VAS score and EQ-5D index
      (both ranging from 0-100) were analyzed in a univariate and multivariate linear
      regression model. RESULTS: The mean EQ-5D index (societal perspective) was 76,
      whereas the mean EQ-VAS (patient perspective) was 66 (P<0.0001). The mean number
      of comorbidities was 4.9 (range 0-11). Dyslipidemia (68%), low back pain (63%)
      and venous insufficiency (57%) were the 3 most frequent co-morbidities. However,
      low back pain (beta= -11.4) and foot problems (beta= -8.5) were significantly
      associated with a reduction in the EQ-VAS score, whereas low back pain (beta= 
      8.4) and coronary heart disease (beta= -24.9) were significantly associated with
      a reduction in the EQ-5D index. CONCLUSION: The number and type of co-morbidities
      determine HRQoL in patients with severe obesity. Within our study population, a
      higher BMI, however, was not associated with a lower quality of life.

PMID- 16105411
TI  - Staged laparoscopic Roux-en-Y: a novel two-stage bariatric operation as an
      alternative in the super-obese with massively enlarged liver.
AB  - In a subset of super-obese patients, the one-stage laparoscopic Roux-en-Y gastric
      bypass (RYGBP) can be associated with significant morbidity and mortality. In a
      previous effort to reduce the perioperative risks associated with the super
      obese, a two-stage operation was devised. This two-stage operation consisted of a
      sleeve gastrectomy (1st stage) followed by a RYGBP or duodenal switch procedure
      (2nd stage). We find that the primary limiting factor making laparoscopic gastric
      bypass challenging in the super-obese is the volume of the left lobe of the
      liver. A greatly thickened left lobe of the liver obscures visualization of the
      gastroesophageal junction and angle of His so that a sleeve gastrectomy is
      difficult to construct. In this report, we describe a novel method utilizing a
      staged Roux-en-Y procedure. Instead of performing a restrictive operation (sleeve
      gastrectomy) as the initial procedure, we fashion a modified Roux-en-Y with a low
      gastrojejunal anastomosis and a larger gastric pouch encompassing the gastric
      fundus. The low anastomosis obviates the need for exposure of the gastro
      esophageal junction and angle of His. At the 2nd stage procedure, completion
      sleeve gastrectomy of the gastric fundus is performed at an interval of 6-12
      months after the 1st stage operation.

PMID- 16105412
TI  - Estimating ideal body weight--a new formula.
AB  - A simple formula for estimating ideal body weight (IBW) in kilograms for both men
      and women is presented. The equation IBW = 22 x H2, where H is equal to patient
      height in meters, yields weight values midway within the range of weights
      obtained using published IBW formulae.

PMID- 16105413
TI  - Reduction of a total propofol consumption in morbidly obese patients during
      general anesthesia due to BIS monitoring.

PMID- 16105415
TI  - Laparoscopic adjustable band combined with duodenal switch article.

PMID- 16105418
TI  - [Mechanical ventilation and heart-lung interaction].

PMID- 16105417
TI  - Avoiding topical anesthesia-induced methemoglobinemia.

PMID- 16105419
TI  - [A review of the casualties by the Japanese chemical weapons abandoned in China
      (1)--introduction of chemical weapon and Japanese chemical weapons abandoned in
      China].

PMID- 16105420
TI  - [Scanning 2005 international consensus on guideline for cardiopulmonary
      resuscitation and emergency cardiovascular care--accident management and first
      aid training].

PMID- 16105421
TI  - [Causes of patient-ventilator asynchrony and its management].

PMID- 16105422
TI  - [Effects of lung protective ventilation in prone or supine position on inhibiting
      adrenomedullin release in acute respiratory distress syndrome caused by pulmonary
      and extra-pulmonary insults in dog].
AB  - OBJECTIVE: To investigate the changes in adrenomedullin release in bronchial
      alveolar lavage fluid (BALF) from different lung areas in acute respiratory
      distress syndrome (ARDS) of produced dogs, by pulmonary and extra-pulmonary
      causes, with low tidal volume and positive end expiratory pressure (PEEP)
      treatment under supine and prone position. METHODS: Twenty-four male mongrel dogs
      were randomly divided into ARDSp (ARDS caused by pulmonary causes) supine group,
      ARDSp prone group, ARDSexp (ARDS caused by extra-pulmonary causes) supine group,
      and ARDSexp prone group. A detergent to cause lung injury in ARDSp dogs, and
      intravenous oleic acid was given in ARDSexp dogs. The results of adrenomedullin
      in different areas of dog's lung (upper lobe, middle lobe, and lower lobe) and
      arterial blood gas under lung protective ventilation treatment were measured.
      RESULTS: After lung injury, the arterial oxygenation index was lowered, and the
      levels of adrenomedullin in the upper lobe and middle lobe of ARDSp dogs were
      higher than that of ARDSexp dogs. After receiving low tidal volume and PEEP
      ventilation, the conditions of all the dogs were gradually getting ameliorated,
      and prone position ventilation gave better effects on lung injury dogs by
      inhibiting adrenomedullin release. CONCLUSION: There are statistical differences
      in adrenomedullin release in different lung areas between ARDSp dogs and ARDSexp
      dogs, and in both ARDSexp dogs and ARDSp dogs low tidal volume and PEEP treatment
      under prone position ventilation give better results compared to supine position.

PMID- 16105423
TI  - [Dynamic changes in airway hyperresponsiveness as a result of allergen and
      therapeutic effects of budesonide in rats].
AB  - OBJECTIVE: To investigate the dynamic changes in airway hyperresponsiveness (AHR)
      in allergen-induced asthma in rats and the effects of budesonide. METHODS: Among
      36 BALB/c female mice, 6 were randomized as negative control group (group C), the
      remaining mice were challenged with ovalbumin (OVA) to reproduce asthma. Kinetics
      of airway AHR of OVA-induced asthmatic mice was carried out as follows: on day
      15, 18, 21 and 25 (A1, A2, A3, A4 groups), 6 mice were randomly chosen and
      sacrificed after measurement of airway AHR to investigate tidal volume (V(T)),
      airway resistance of expiring phase (R(A)), compliance of thorax and lung (C(T
      L)) with different doses of methacholine chloride (MCH). In group B 6 mice were
      randomly chosen and treated with 1 mg budesonide aerosol once per day from day 15
      to 17, then sacrificed on day 18. Their physiological and pathological changes
      were determined similarly to those of A2 group. RESULTS: (1) The increase of R(A)
      in group A1, A2 and A3 were significantly higher than that in group C when MCH
      reached the dose of 200 ng/g. (2) The decrease of C(T-L) in group A1 and A2 was
      significant with 100 ng/g and 200 ng/g MCH. (3) The value of V(T) markedly
      decreased in group A2 with 100 ng/g MCH and in all asthma model groups with 200
      ng/g MCH than that in group C. (4) There was an eosinophil-dominant inflammatory
      infiltration in the asthma lungs, and the degree of infiltration peaked on day
      15, and then alleviated afterwards. (5) With the dose of 200 ng/g MCH, the
      increase of R(A) in group B was significantly alleviated when compared with that
      in group A2, but there was no significant difference between group B and C. With
      the dose of 100 and 200 ng/g MCH, the decrease of C(T-L) in group B was
      significantly less marked compared with that in group A2 but there was no
      significant difference between group B and group C; the decrease of V(T) in group
      B was significantly lessened in degree when compared with that in group A2, while
      there was no statistical difference between group B and group C. The infiltration
      of inflammatory cells was obviously alleviated and the repair of airway
      epithelium was better in budesonide group. CONCLUSION: (1) Airway
      hyperresponsiveness increases greatly in mice challenged and sensitized with OVA,
      and it lasts for about 7 days and then declines afterwards. (2) Budesonide
      aerosol could effectively alleviate the eosinophil dominant inflammatory response
      and decrease AHR in the murine asthma model.

PMID- 16105424
TI  - [Experimental study of the safety of sustained inflation strategy in acute
      respiratory distress syndrome in sheep].
AB  - OBJECTIVE: To evaluate the effects of lung recruitment maneuver (RM) on
      hemodynamics and lung structure with sustained inflation (SI) in acute
      respiratory distress syndrome (ARDS) in sheep, to look for a safe range of
      pressure and time of SI. METHODS: Fourteen anaesthetized sheep were subjected to
      lung lavage through a broncho-fibroscope to reproduce ARDS, and quasi-static
      pressure-volume (P-V) curves were obtained with low flow technique. The upper
      inflection point (UIP) and the lower inflection point (LIP) were found, and then
      5 cm H(2)O (1 cm H(2)O=0.098 kPa) below UIP, UIP, 10 cm H(2)O above UIP, 20 cm
      H(2)O above UIP as the peak pressure of SI were selected as the test pressure.
      They were randomized to four groups (U-5, U+0, U+10, U+20). The duration of SI
      was 60 seconds. Hemodynamics and oxygenation indexes were monitored and recorded
      during and after SI until the study was terminated 2 hours later, then CT and
      lung tissue biopsy were performed. RESULTS: Pneumothorax was found in U+20
      groups, resulting in the death of sheep. Hemodynamics was affected significantly
      in other groups during SI. In U+10 groups, cardiac output (CO) and cardiac index
      (CI) were lowered at 15 seconds after RM began, and recovered slowly after RM; in
      U+0 group and U-5 group, the entire RM could be carried out to the end, and
      biopsy showed bullous emphysema in U+0 group. CONCLUSION: The impairment of the
      hemodynamics and damage to the lung structure should be prevented when RM is
      performed in ARDS patients, and the inflation pressure should be limited within
      the range of UIP or 5 cm H(2)O under UIP to avoid adverse effect on hemodynamics.

PMID- 16105425
TI  - [Effects of recruitment maneuvers with low tidal volume ventilation in patients
      with acute respiratory distress syndrome].
AB  - OBJECTIVE: To assess the effects of recruitment maneuvers (RMs) with low tidal
      volume (V(T)) ventilation on gas oxygenation and reduction of ventilation
      associated lung injury (VALI) in patients suffering from acute respiratory
      distress syndrome (ARDS), to assess the effects of RMs on blood pressure, heart
      rate and occurrence of barotrauma. METHODS: Patients in intensive care unit (ICU)
      of Beijing Fuxing Hospital were randomized into two groups: low V(T)+RM group and
      low V(T) without RM group (non-RM group). Twenty-eight patients with early ARDS
      admitted from January 2003 to March 2004 were enrolled in the study. All patients
      received protective ventilation: V(T) was set at 6 ml/kg with plateau pressure
      limited at 30 cm H(2)O (1 cm H(2)O=0.098 kPa) or lower, positive end-expiratory
      pressure (PEEP) and fraction of inspired oxygen (FiO(2)) were set to obtain an
      partial pressure of arterial oxygen (PaO(2)) between 60 to 80 mm Hg (1 mm
      Hg=0.133 kPa). RMs were conducted by regulating FiO(2) to 1.00, applying 40 cm
      H(2)O of continuous positive airway pressure (CPAP) for 40 seconds, and then
      resumed the previous ventilator settings (mode, PEEP, and FiO(2)). This modality
      was repeated once every 8 hours for a total of 5 days. Measurements of
      PaO(2)/FiO(2), serum interleukin-6 (IL-6) concentration, respiratory and
      radiographic data, and ventilatory parameters were obtained at baseline and for
      the first 5 days. Mean arterial pressure and heart rate and pulse oxygen
      saturation (SpO(2)) were measured before and after the RM. The primary outcome
      was mortality at 28 days. RESULTS: (1) After RM, PaO(2)/FiO(2) and PaO(2) in RM
      group and non-RM group increased, but the values were higher in RM group, and the
      difference between two groups was significant (all P<0.05). (2) IL-6
      concentrations decreased in both groups but lower in RM group with significant
      difference (P<0.05). (3) Barotrauma did not occur in both groups. (4) No
      significant changes in blood pressure and heart rate were found during RMs. HR
      and MAP remained unchanged after RM. CONCLUSION: RM could recruit the collapsed
      alveoli in ARDS. It could significantly improve oxygenation and decrease VALI. A
      superimposed RM is safe, and repeated RM could also decrease barotrauma.

PMID- 16105426
TI  - [Prospective randomized controlled clinical study of early use of noninvasive
      positive pressure ventilation in the treatment for acute exacerbation of chronic
      obstructive pulmonary disease].
AB  - OBJECTIVE: To evaluate the effect of the early use of noninvasive positive
      pressure ventilation (NIPPV) on gas exchange, rate of endotracheal intubation and
      in-hospital mortality in patients with acute exacerbation of chronic obstructive
      pulmonary disease (COPD). METHODS: Thirty-six patients with acute exacerbation of
      COPD [7.25< or =arterial blood pH (pHa)<7.35, partial pressure of carbon dioxide
      in artery (PaCO(2))>45 mm Hg, 1 mm Hg=0.133 kPa] were enrolled in the study. The
      patients were divided randomly into standard therapy group (group A, n=18) and
      standard therapy+NIPPV group (group B, n=18). The patients in group A were
      treated with standard therapy only and those in group B were treated with both
      standard therapy and NIPPV with Bi-level positive airway pressure (BiPAP) mode.
      NIPPV should be maintained over 2 hours in the first time. In the first 3 days,
      the duration of NIPPV should not be less than 8 hours per day. In each group,
      heart rate (HR), respiratory rate (RR), parameters of gas exchange, and scale for
      accessory muscle use were measured at the time of enrollment (0 hour), 2 hours,
      24 hours and 72 hours after randomization. In group B, the foregoing parameters
      were also observed at 24 hours after the end of NIPPV. Rate of endotracheal
      intubation and in-hospital mortality were recorded in each group. RESULTS: The
      general conditions were similar in both groups at 0 hour. Compared with that of 0
      hour, marked improvement in HR, RR, pHa, PaCO(2) and scale for accessory muscle
      use was found only at 72 hours after treatment in group A. In group B,
      significant improvement in HR, RR, PaCO(2), partial pressure of oxygen in artery
      (PaO(2)) and scale for accessory muscle use was found 2 hours after the
      treatment. In this group, the foregoing parameters were improved continuously in
      the course of the treatment, and they showed no deterioration 24 hours after
      termination of NIPPV. The rate of endotracheal intubation in group B (11.1%) was
      significantly lower than that in group A (44.4%, P<0.05). In group B, the in
      hospital mortality was slightly lower than that in group A (5.6% vs. 16.7%,
      P>0.05). CONCLUSION: Early use of NIPPV can improve gas exchange, lessen
      respiratory muscle fatigue and decrease the need for intubation in patients with
      acute exacerbation of COPD.

PMID- 16105427
TI  - [Clinical comparative study of airway pressure release ventilation and continuous
      positive airway pressure ventilation].
AB  - OBJECTIVE: To evaluate the effects of airway pressure release ventilation (APRV)
      and continuous positive airway pressure (CPAP) on hemodynamics, lung mechanics
      and oxygen metabolism index. METHODS: Fifteen ARDS cases ventilated and monitored
      by the pulse contour method (PiCCO) were randomized into APRV group and CPAP
      group, then lung recruitment maneuver (RM) was executed every 4 hours. In APRV
      group, Phigh was 35 cm H(2)O (1 cm H(2)O=0.098 kPa) and Plow was set at lower
      inflection point (LIP) of the static pressure-volume (P-V) curve. In CPAP group,
      CPAP was also 35 cm H(2)O. The duration of RM in both groups was 40 seconds.
      Before and after RM the parameters of lung mechanics, oxygen metabolism index and
      hemodynamics were monitored and compared. RESULTS: (1) In APRV group cardiac
      index (CI) was decreased slightly during RM with shorter duration than CPAP
      group. (2) The parameters of lung mechanics and oxygenation were improved
      significantly in both groups, and they were better in APRV group than CPAP group.
      CONCLUSION: In APRV group sedation can be abstained during RM, and the
      hemodynamics were hardly disturbed. Improvement of lung mechanics and oxygenation
      is much better with APRV than CPAP mode.

PMID- 16105428
TI  - [Effects of lung recruitment maneuver on oxygenation and hemodynamics after open
      endotracheal suctioning in acute respiratory distress syndrome].
AB  - OBJECTIVE: To evaluate the treatment value of lung recruitment (LR) maneuver on
      oxygenation and hemodynamics in acute respiratory distress syndrome (ARDS)
      patients after open endotracheal suctioning (ETS). METHODS: Twenty ARDS/acute
      lung injury (ALI) patients requiring mechanical ventilation support were
      randomized into two groups after stabilizing for 30 minutes. Group 1: LRs were
      performed immediately after ETS (ETS+LR), and then ETS was repeated after 60
      minutes without LR. Group 2: the first ETS was performed without LR (ETS-LR), and
      the second ETS was combined with LR after 60 minutes. Partial pressure of oxygen
      in artery (PaO(2)), central venous pressure (CVP), heart rate (HR) and mean
      arterial pressure (MAP) were serially measured during the procedure. RESULTS: The
      hemodynamic parameters were stable in all patients, and no arrhythmia occurred.
      PaO(2) decreased significantly after ETS, but recovered rapidly in 5 and 15
      minutes after LR (both P<0.05). CONCLUSION: LR is effective in rapidly
      counteracting the deterioration in PaO(2) caused by open ETS in ARDS/ALI patients
      without interfering the hemodynamics.

PMID- 16105429
TI  - [Role of prone position mechanical ventilation in patients with acute respiratory
      distress syndrome originating from pulmonary disease and extra-pulmonary
      disease].
AB  - OBJECTIVE: To assess the effect of mechanical ventilation on prone position for
      the treatment of acute respiratory distress syndrome (ARDS) originating from
      pulmonary disease and extra-pulmonary disease. METHODS: From January 2001 to
      February 2004 in intensive care unit (ICU), 42 patients with ARDS were divided
      into pulmonary disease group and extra-pulmonary disease group. All the patients
      were mechanically ventilated on prone position. Arterial blood gases, respiratory
      rate (RR), fraction of inspired oxygen (FiO(2)), pulmonary compliance (C), tidal
      volume (V(T)), airway resistance (Raw) were measured before prone position and 2
      hours and 4 hours after prone position. Lung-CT was measured in supine position
      and prone position. RESULTS: When patients were turned to prone position, SaO(2)
      and RR were decreased markedly in two groups. V(T) was increased in extra
      pulmonary disease groups compared with pulmonary disease group at the same time.
      Oxygen index, hemoglobin oxygen saturation and Raw were increased markedly when
      patients were turned to prone position, and oxygen index of pulmonary disease
      group was higher than that of extra-pulmonary disease group at the same time. No
      change was found in blood pH and partial pressure of carbon dioxide in artery
      (PaCO(2)), but oxygenation was improved markedly in two groups. The effective
      rate of improved oxygenation was 65% in pulmonary disease group and 68% in
      extrapulmonary disease group, but no significant difference was found. Lung CT
      revealed that when the patients were in prone position, the degree of lung
      infiltration in the dorsal part of lung decreased while that in the ventral part
      increased. CONCLUSION: Oxygenation is improved markedly in prone position in two
      groups. Mechanical ventilation on prone position was an effective method in the
      treatment of ARDS patients.

PMID- 16105431
TI  - [Suggestive guideline for respiratory support in emergency--stepwise breath
      management].
AB  - OBJECTIVE: To propose a guideline of respiratory support for emergency patients.
      METHODS: To summarize the experiences gained in giving stepwise respiratory
      support (SRS) in 2,548 patients for emergency care (including 1,823 trauma
      patients and 725 non-trauma patients) between 1992 to 2002. RESULTS: There were
      1,876 male and 672 female patients with the ratio of male to female 2.79:1. The
      age of patients ranged between 4 to 86 years, and the mean age of traumatic
      patients was (32.3+/-19.8) years, and the dominant ages were between 20 to 39.
      The mean age of non-traumatic patients was (65.2+/-17.3) years, and the dominant
      ages were between 50 to 69. The traumatic and non-traumatic patients accounted
      for 60.2% and 32.0% of all patients, respectively. The respiratory management
      included resuscitation positioning in 816 (32.0%), open airway and suctioning in
      314 patients (12.3%), oxygenation through nostril or nasal intubation in 2,311
      patients (90.7%), oxygenation by mask in 124 patients (4.9%), endotracheal
      intubation in 254 patients (10.0%), thyrocricocentesis or cricothyrotomy in 25
      patients (1.0%), tracheotomy in 195 patients (7.7%), percutaneous tracheotomy in
      58 patients (2.3%). SRW management included two types, four steps and ten ways.
      The two types included traumatic and non-traumatic; the four steps and ten ways
      included first step of manual treatment (including (1) resuscitation positioning,
      (2) open airway and suction and (3) chest-back press), second step oxygenation
      (including (4) oxygenation through nostril or nasal intubation, (5) oxygenation
      by mask, (6) endotracheal intubation), third step invasive airway support
      (including (7) thyrocricocentesis or cricothyrotomy and (8) tracheotomy or
      percutaneous tracheostomy), fourth step mechanic ventilation (covering (9) manual
      ventilation and (10) mechanical ventilator). CONCLUSION: The series of SRS
      management plan and principles can improve the respiratory support in rescuing
      emergency patients efficiently.

PMID- 16105433
TI  - [Study of small dural window exposure strategy for preventing intraoperative
      acute brain herniation during removal of huge intracranial meningiomas].
AB  - OBJECTIVE: To investigate and assess the value of small dural window exposure
      strategy on preventing brain herniation during the operation for huge
      intracranial meningiomas. METHODS: Different classical operative approaches were
      used for the removal of intracranial meningiomas situated in different locations.
      When the dura was found to be under high tension, it was imperative that measures
      should be taken to prevent damage to the brain tissue in the important cortical
      areas as a result of acute intraoperative brain swelling and herniation. The
      strategy to be taken was to make a small dural window for exposure, thus the dura
      was used as a natural barrier to prevent acute brain swelling and herniation. The
      concept was to tailor the location and size of the dural opening to the location
      and size of the tumor, so that through the window only a part of the tumor was
      exposed, without exposing any important structures, such as bridging veins to the
      sagittal sinus and middle cerebral artery in the Sylvian fissure or any part of
      brain tissue initially. When necessary only a part of non-important brain tissue
      adjacent to the tumor could be exposed. Through this small dural window a huge
      tumor could be removed piecemeal till the high pressure under the dura was
      relieved. Then the dura could be opened more to remove the whole tumor. RESULTS:
      In 6 consecutive cases with extremely high tension under the dura, total tumor
      removal was successfully performed with complete avoidance of the risk of acute
      intraoperative brain swelling and herniation, and all the patients had uneventful
      recovery, and they were able to resume normal life. The locations of the said
      tumors were: in parasagittal falx region in 2 cases, and 1 case each in sphenoid,
      cerebellopontine angle, middle cranial fossa and temporal convexity region.
      CONCLUSION: The small dural window exposure strategy can guarantee safe total
      removal of huge intracranial meningiomas avoiding the risk of acute
      intraoperative brain swelling and herniation. Peritumorous brain tissue can be
      kept intact. Preoperative spinal drainage of cerebrospinal fluid for lowering
      intracranial pressure is unnecessary in the majority of such cases. Some new
      knowledge for our understanding the etiological mechanisms and the mechanisms of
      the surgical strategy to avoid acute intraoperative brain swelling and herniation
      in removal of huge intracranial meningiomas can be learned.

PMID- 16105442
TI  - [Prevention and control of pesticide poisoning is an important and long-term
      task].

PMID- 16105443
TI  - [Detection of hydrogen phosphide in blood and lung tissue of patient with acute
      hydrogen phosphide poisoning].

PMID- 16105444
TI  - [Relationship between the polymorphism of carboxylic esterases and genetic
      susceptibility to organophosphates pesticides exposure].
AB  - OBJECTIVE: To study the relationship between the polymorphism of
      butyrylcholinesterase (BChE, EC 3.1.1.8) and paraoxonase (PonE, EC 3.1.8.1), and
      the individuals' genetic susceptibility to organophosphates pesticides (OPs)
      exposure. METHODS: 75 OPs exposure workers were selected to determine their BChE
      K, PON-192 and PON-55 genotypes using PCR-RFLP. The accumulative symptom scores
      and the whole blood acetylcholinesterase activity (mmol x h(-1) x ml(-1)) were
      used as health index. Firstly, the health condition related to single gene site
      of the three gene loci was analyzed to determine which kinds of genotype were
      susceptible. Then, used the multiple variance analysis was to see if there
      existed interactions among these three gene loci. Finally, established the multi
      factor linear regression equation, in which considered some other factors that
      might influence the health situation such as age, gender and the exposure time.
      According to the equation, could get the accumulative symptom scores of each kind
      of subpopulation of different genotypes. RESULTS: The mean AChE activities of the
      exposed workers with BChE-K genotype UU (61 cases), genotype UK (12 cases) and
      genotype KK (2 cases) were 105.0 +/- 23.0, 84.4 +/- 16.4, 79.0 +/- 9.9,
      respectively; The accumulative symptom scores were 3.7 +/- 3.8, 9.2 +/- 3.0, 12.5
      +/- 0.7, respectively. The AChE activities of the exposed workers with PON-192
      genotype BB (37 cases), genotype AB (27 cases) and genotype AA (11 cases) were
      116.8 +/- 15.1, 91.2 +/- 15.6, 72.3 +/- 21.4, respectively; The accumulative
      symptom scores were 2.0 +/- 3.2, 6.7 +/- 3.3, 9.7 +/- 1.8, respectively.
      Similarly, the AChE activities of the exposed workers with PON-55 genotype LL (70
      cases) and genotype LM (5 cases) were 102.4 +/- 23.0, 82.8 +/- 22.0; The
      accumulative symptom scores were 4.5 +/- 4.2, 9.2 +/- 3.6, respectively. Single
      variance analysis showed that the accumulative symptom scores of the individuals
      with abnormal homozygote of these three gene loci were the highest, which
      indicated that they were most susceptible to OPs. Multiple variance analysis
      showed there were no interactions among the three gene loci. Age, gender and
      exposure time had no statistical significance, while genotypes of the three gene
      loci had statistical significance to health situation. CONCLUSION: Genotypes of
      BChE-K, PON-192 and PON-55 are related to susceptibility to OPs exposure.

PMID- 16105445
TI  - [Effects of carbaryl production exposure on the sperm and semen quality of
      occupational male workers].
AB  - OBJECTIVE: To analyse the male reproductive toxicity of carbaryl. METHODS: Thirty
      one male carbaryl exposure workers and 46 male administrators in the office in a
      pesticide factory were selected as the exposure group and internal control group
      respectively, and 22 male administrators in a center for disease control and
      prevention were served as the external control group. In order to evaluate the
      exposure levels, the concentrations of carbaryl, methyl isocyanate, ammonia and
      phenol in the ambient air of the work place in these three groups were monitored
      simultaneously for three consecutive days. Moreover, three workers in the
      exposure group and the external control group were selected to evaluate the
      amount of carbaryl of individual and dermal contamination for three consecutive
      days. After the semen were collected according to the standard method, the
      workers'semen qualities were analysed with WHO method, the sperm morphology and
      the sperm motility were evaluated using micro-cell slide spectrum technology and
      computer assisted sperm analysis (CASA) respectively. RESULTS: In the exposure
      group, the concentrations of carbaryl and phenol (52.41 mg/m(3) and 0.08 mg/m(3)
      respectively) were significantly higher than those in the internal and external
      control group (P < 0.01 or P < 0.05). Furthermore, in the carbaryl exposure area
      the geometric mean concentration of carbaryl with the individual sampling was
      7.38 mg/m(3), and the geometric mean of dermal contamination detected in the
      carbaryl exposure area was 862.47 mg/m(2). Carbaryl was not found in the external
      control area (P < 0.01). The seminal volume [(2.39 +/- 1.44) ml] and the sperm
      motility [(1.77 +/- 0.61) grade] were significantly lower than those in the
      external control group (P < 0.05), and sperm motion parameters such as linearity
      (LIN, 39.89% +/- 6.00%), straightness (STR, 71.51% +/- 11.22%), straight line
      velocity [VSL, (26.29 +/- 7.84) microm/s] and beat cross frequency [BCF, (3.99 +/
      1.55) Hz] were lower than those in the internal and external control group (P <
      0.05), while the abnormal rates of viscidity, sperm motility and total aberration
      rate were higher than those in the external control group (P < 0.05). CONCLUSION:
      Occupational exposure to carbaryl production can affect the workers'sperm and
      semen quality to certain extent.

PMID- 16105446
TI  - [Therapeutic efficacy of pralidoxime chloride on acute dichlorvos poisoning].
AB  - OBJECTIVE: To study the therapeutic efficacy and mechanism of oxime drug,
      pralidoxime chloride (PAM-Cl), on acute dichlorvos (DDV) poisoning. METHODS: The
      toxic signs and survival rate were recorded and ChE activity in blood was
      determined in treatment group with PAM-Cl and non-treatment group after DDV was
      given to rats and mice by gastrogavage; the therapeutic efficacy and reactivation
      of DDV-inhibited ChE by PAM-Cl were observed on the patients with acute DDV
      poisoning. RESULTS: (1) The alleviated and delayed toxic signs as well as higher
      survival rate were found in PAM-Cl treatment group compared with non-treatment
      group. (2) After the rats were exposed to DDV, the ChE activities of whole blood
      in different time within 24 h were statistically significantly higher in PAM-Cl
      treatment group than in non-treatment group (P < 0.05). (3) After PAM-Cl
      treatment, muscular fasciculation and other nicotinic signs in poisoned patients
      were disappeared and the inhibited blood ChE activities were gradually
      reactivated to normal level. CONCLUSION: PAM-Cl has therapeutic efficacy against
      acute toxicity of DDV through its reactivation of inhibited ChE.

PMID- 16105447
TI  - [Therapeutic efficacy of N6-cyclopentyladenosine against acute dichlorvos
      poisoning].
AB  - OBJECTIVE: To study the therapeutic efficacy and mechanism of adenosine receptor
      agonist N(6)-cyclopentyladenosine (CPA) against acute dichlorvos poisoning.
      METHODS: Soon after a certain doses of dichlorvos were given to mice and rats by
      gastrogavage, physiological saline, CPA, atropine or pralidoxime chloride were
      administered to different groups. Toxic signs and survival rate were recorded and
      cholinesterase (ChE) activities and acetylcholine (ACh) concentrations in whole
      blood were determined in treatment group with CPA and non-treatment group after
      dichlorvos was given to rats by gastrogavage. RESULTS: (1) The alleviated and
      delayed appearance of toxic signs as well as obvious prolongation of survival
      time was observed in CPA treatment group compared with non-treatment group. (2)
      ChE activities in both treatment group with CPA [(0.49 +/- 0.05) U/ml] and non
      treatment group [(0.52 +/- 0.04) U/ml] were significantly lower than that [(1.56
      +/- 0.15) U/ml] of the control group (P < 0.01), but there was no significant
      difference between treatment group and non-treatment group (P > 0.05). (3) ACh
      concentration [(204.24 +/- 20.48) microg/ml] in whole blood of treatment group
      with CPA was significantly lower than that [(230.91 +/- 25.61) microg/ml] of non
      treatment group (P < 0.05). CONCLUSION: CPA has therapeutic efficacy against
      acute dichlorvos poisoning, which is probably through the decrease in ACh
      concentration.

PMID- 16105448
TI  - [Oxidative stress of deltamethrin on rat nervous system].
AB  - OBJECTIVE: To explore the lipid peroxidation induced by deltamethrin (DM) in the
      cerebral cortex and hippocampus of rat. METHODS: Wistar male rats were
      administrated with DM (daily dose was 3.125, 12.500 mg/kg respectively). The
      content of malondialdehyde (MDA) and the activity of total-superoxide dismutase
      (T-SOD, including Mn-SOD and CuZn-SOD), catalase (CAT), glutathione-S-transferase
      (GST), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) in cerebral
      cortex and hippocampus tissue were determined. The reduced glutathione (GSH)
      content and gamma-glutamylcysteine synthetase (gamma-GCS) activity in cytosolic
      fraction of cerebral cortex and hippocampus tissue was determined by reversed
      phase high performance liquid chromatographic assay with o-phthalaldehyde pre
      column derivation. RESULTS: (1) MDA content in cerebral cortex of the high dose
      group was significantly higher than those in the low dose group, and MDA content
      in hippocampus tissue of the high dose group was significantly higher than those
      in both the control and the low dose group after 5 d of DM exposure. (2) The
      activity of T-SOD and CuZn-SOD in cerebral cortex of both high and low dose group
      were significantly lower than that in the control group, and there was no effect
      on CAT activity in cerebral cortex (P < 0.01 or P < 0.05). (3) GSH content in
      cerebral cortex of the high dose group was significantly higher than that in
      control group (P < 0.05), and that in hippocampus tissue of high dose was
      significantly lower than that in both control and low dose group (P < 0.05). GR
      activity of low dose group in cerebral cortex was significantly lower than that
      in both control and high group [(11.80 +/- 5.15) vs (18.98 +/- 3.68), (17.35 +/-
      2.47) U/mg pro] (P < 0.01). Gamma-GCS activity in hippocampus tissue of the high
      dose group was significantly lower than that in both control and low dose group
      [(1.75 +/- 0.60) vs (3.17 +/- 0.79), (2.72 +/- 0.75) nmol x mg pro(-1) x min(-1)]
      (P < 0.01). GR activity in hippocampus tissue of both high and low dose group was
      significantly lower than that in the control group [(21.63 +/- 4.92), (21.46 +/-
      8.89) vs (31.22 +/- 6.97) U/mg pro] (P < 0.05). CONCLUSION: The oxidative stress
      in nerve tissue, which could be resulted from effect of DM on the activity of
      SOD, gamma-GCS and GR and GSH content, is one of the mechanisms of neuro-toxicity
      induced by DM; The decreased activity of gamma-GCS and GR may be the primary
      cause of DM-induced decrease in that GSH content in hippocampus tissue.

PMID- 16105449
TI  - [Effects of methamidophos on microtubule and microfilament proteins in sciatic
      nerve of hens].
AB  - OBJECTIVE: To investigate the dynamic changes of alpha-tubulin, beta-tubulin and
      beta-actin in sciatic nerve of hen with organophosphorus ester-induced delayed
      neuropathy (OPIDN). METHODS: OPIDN was induced in 10-month-old Roman hens by
      daily subcutaneous administration of 30 mg/kg methamidophos for 15 days. Hens
      were sacrificed 2, 10, and 23 days respectively after manifesting neuropathy. The
      sciatic nerves were dissected, homogenized and used for the determination of the
      alpha-tubulin, beta-tubulin and beta-actin levels by western blotting. RESULTS:
      The levels of alpha-tubulin in supernatant of sciatic nerves were decreased by
      6%, 15% and 25% respectively on day 2, 10 and 23 respectively, while those in
      pellet remained almost unchanged. beta-tubulin were decreased by 27%, 6%, 19% in
      pellet and 1%, 21%, 22% in supernatant of sciatic nerves on 2, 10 and 23 days.
      Beta-actin level in pellet of sciatic nerve increased by 24%, 48% and 17% on day
      2, 10 and 23, and little changes were observed in supernatant. CONCLUSION:
      Methamidophos may induced changes of alpha-tubulin, beta-tubulin and beta-actin
      levels in sciatic nerve of hen, which may be one of the mechanism of the
      contribution to the occurrence and development of OPIDN.

PMID- 16105450
TI  - [Early change of pulmonary ventilation in new coal miners].
AB  - OBJECTIVE: To study the early effects of coal dust on lung function in new
      underground coal miners. METHODS: Two hundred and eighty-seven male miners were
      selected from new employees at the Xuzhou Mining Group Company as study group,
      and 132 male students at a mining technical school were selected as control. Data
      collection included: individual demographic parameters, family medical history,
      occupational history, and smoking history, measurement of dust concentrations in
      work areas, and lung function tests. This prospective cohort study took place
      over 3 years during which time total dust and respirable dust concentrations in
      the new coal miners' work areas were measured twice each month. For both miner
      and student groups, FVC and FEV(1) were tested initially before dust exposure,
      and then 15 times over the 3 years. RESULTS: The average total dust and
      respirable dust concentrations in the miners' work areas were 23.8 mg/m(3) and
      8.9 mg/m(3) respectively, which greatly exceeded national health criteria. During
      the first year of dust exposure, the miners's average FVC was higher than that of
      the controls (5.19 L vs 4.92 L, P < 0.01). During the 2nd and 3rd year the
      difference in average FVC between miners and control group was not significant
      (5.14 L vs 5.12 L, P > 0.05). Before dust exposure, the miners' FEV(1) was
      significantly higher than that of the control group (4.48 L vs 4.28 L). In the
      miners group, FEV(1) declined rapidly during the first year following dust
      exposure (from 4.48 L to 4.25 L), and in the 2nd and the 3rd year the average
      FEV(1) of the miners was significantly lower than that of controls (4.34 L vs
      4.56 L, P < 0.01), although there were some fluctuations during the follow-up
      period. Overall, the average FEV(1) of miners group showed a significant decline
      during the study. There were significant correlations between FVC or FEV(1) and
      age, height, weight, and smoking. The three-year total loss of FVC and FEV(1) in
      smoking miners (154 ml, 184 ml) were greater than in non-smoking miners (83 ml,
      91 ml). CONCLUSION: There are apparent effects of coal dust on lung function in
      new underground coal miners, with FEV(1) being more impacted than FVC. Smoking
      may aggravate the effect of dust exposure on reducing lung function.

PMID- 16105451
TI  - [Transforming growth factor-beta1 induced phenotypic differentiation of human
      lung fibroblasts through mitogen activated protein kinase-dependent pathway].
AB  - OBJECTIVE: To investigate the role of MAPK signal transduction in TGF-beta1
      induced phenotypic differentiation of human lung fibroblasts. METHOD: Human lung
      fibroblasts cell line (HLF-02) were cultured and then stimulated with 10 ng/ml
      TGF-beta1 for different time; SB203580 or PD98059 was added into culture medium
      to prevent p38 or Erk kinase pathway before incubating with TGF-beta1; the
      expression of alpha-smooth muscle actin (alpha-SMA) was detected by Western
      blotting and RT-PCR; Western blotting was used to assay phosphorylation of p38,
      Erk, and JNK kinase. RESULTS: (1) In the process of stimulation by TGF-beta1, the
      alpha-SMA mRNA expression levels of 24, 48 and 72 h groups were 1.87 +/- 0.11,
      2.49 +/- 0.10, 3.02 +/- 0.15 respectively; and the alpha-SMA protein expression
      levels of 24, 48 and 72 h groups were 3.20 +/- 0.14, 3.96 +/- 0.21, 4.57 +/- 0.13
      respectively. (2) TGF-beta1 induced p38, Erk kinase phosphorylation but not JNK
      kinase. (3) The inhibitors SB203580 and PD98059 suppressed TGF-beta1-induced p38
      kinase and Erk phosphorylation respectively. (4) SB203580 significantly
      attenuated TGF-beta1-induced alpha-SMA mRNA and protein expression (inhibition
      rate: 30% and 40%); PD98059 also significantly inhibited TGF-beta1-induced alpha
      SMA mRNA and protein expression (inhibition rate: 10% and 20%). CONCLUSION: TGF
      beta1 is capable of inducing the phenotypic differentiation of HLF-02, which is
      regulated by p38 and Erk kinase signal pathway.

PMID- 16105452
TI  - [The influence of occupational exposure and smoking on lung ventilation of coke
      oven workers].
AB  - OBJECTIVE: To study the influence of occupational exposure and smoking on lung
      ventilation function of coke oven workers. METHODS: Environmental monitoring was
      performed on the top, side and bottom of some coke ovens. Lung ventilation
      function test was performed in 234 coke oven workers. RESULTS: The poison
      concentration in environment had such tendency as it was the highest on the top,
      then the side, and the lowest at the bottom. The standardized forced expiratory
      volume in the 1st second (FEV(1), 90.8% +/- 8.6%) and forced expiratory rate
      (FEV(1)%, 95.4% +/- 12.4%) of those coke oven workers who smoked were
      significantly lower than those non-smoking workers (100.9% +/- 14.3%, 108.9% +/-
      17.6%); among those smoking workers, the partial correlation coefficients between
      forced vital capacity (FVC) and benzene soluble, benzopyrene, and smoking index
      were -0.249, -0.187 and -0.368 respectively; and the coefficients between FEV(1)
      and the three aspects were -0.255, -0.191 and -0.388; and the coefficients
      between FEV(1)% and them were -0.131, -0.107 and -0.065. Among those non-smoking
      workers, the coefficients between benzene solubles and FVC, FEV(1) and FEV(1)%
      were -0.154, -0.052 and -0.176, and between benzopyrene and them were -0.121, 
      0.037 and -0.159. CONCLUSION: The lung ventilation function of coke oven workers
      has certain negative correlation with both occupational exposure and smoking.

PMID- 16105453
TI  - [Coal worker's pneumoconiosis with esophagitis of Candida albicans].

PMID- 16105454
TI  - [Effects of taurine on the expression of nitric oxide synthase in lung of rats
      exposed to silica].
AB  - OBJECTIVE: To evaluate the effects of taurine in diet on the expression of
      inducible nitric oxide synthase (iNOS) in rat lung induced by silica. METHODS:
      Wistar rats were established by direct tracheal instillation of silica into rat
      lungs exposed surgically, and the animals of taurine-treated group were silica
      instilled with a diet containing taurine. The taurine concentration of serum was
      analyzed by means of HPLC. The expression of iNOS protein in paraffin-embedded
      lung sections with Streptavidin/peroxidase (SP) immunohistochemistry on tissue
      microarray was measured by Image-Pro Plus. RESULTS: The concentration of taurine
      in serum of taurine-treated group was significantly higher than those in saline
      treated and silica-treated groups (P < 0.05). The activities of total NOS and
      iNOS in BALF supernatant and iNOS positive area percentage of rat lung in silica
      treated group were at the peak on 14th day, which were 1.84 U/ml, 1.12 U/ml and
      5.42% more respectively than those in saline-treated group (P < 0.05). There were
      no significant differences between taurine-treated group and silica-treated group
      in total NOS and iNOS activities of BALF supernatant, and iNOS positive area of
      the lung (P > 0.05). CONCLUSION: Treatment with taurine hardly influences on the
      increase in expression of nitric oxide synthase in rat lung induced by silica
      dust.

PMID- 16105455
TI  - [Effect of prostaglandin E2 and the tumor necrosis factor-alpha on second
      messenger of lung fibroblast].
AB  - OBJECTIVE: To Study the effect of prostaglandin E(2) (PGE(2)) combined with tumor
      necrosis factor-alpha (TNF-alpha) on the second messenger of mouse lung
      fibroblast in order to research new target point for cytokine to treatment of
      pneumoconiosis. METHODS: The lung fibroblasts of breed mouse were primarily
      cultured. 10 ng/ml TNF-alpha and 10 ng/ml TNF-alpha combined with PGE(2) of
      different doses were added to culture medium of fibroblasts. The gamma value and
      CPM value were respectively measured for second messenger of cAMP, cGMP and IP(3)
      of fibroblast by immune-radio assay at different observation time. RESULTS: When
      treated with 10 ng/ml TNF-alpha + 1,000 pg/ml PGE(2) at 120 s time points, the
      CPM value of IP(3) of fibroblast was the maximal value [(76.33 +/- 7.10) CPM];
      when cAMP/cGMP ratio declined to 4.29 at 24 h time point, the effect of
      fibroblast proliferation was the strongest; when 10 ng/ml TNF-alpha + 500 pg/ml
      PGE(2), and 2 000 pg/ml PGE(2), the CPM value of IP(3) of fibroblast were 27.00
      +/- 3.00 and 61.00 +/- 2.65 respectively at 120 s time point, cAMP/cGMP value
      were 3.50 and 9.83 respectively at 24 h, the effect on fibroblast proliferation
      were obviously lower. CONCLUSION: Certain dose of PGE(2) could raise the ratio of
      cAMP/cGMP of fibroblast, and antagonize the proliferation effect of TNF-alpha on
      fibroblast.

PMID- 16105456
TI  - [Expression of novel environmental responsive protein JWA involved in the
      oxidative stress responsiveness in MCF-7 cells].
AB  - OBJECTIVE: To study the expression and the possible role of JWA protein in
      oxidative stress-induced damage of MCF-7 cells, especially the relationship
      between JWA and heat shock proteins (HSPs). METHODS: MCF-7 cells were exposed to
      different concentration of H(2)O(2) (0.01,0.10, 1.00 mmol/L) for different time
      (10, 30, 60 and 180 min) respectively. DNA damage was detected by using DNA gel
      electrophoresis. The MTT assay was used to analyze the effect of H(2)O(2) on the
      cytotoxicity and relative cell proliferation ratio of the cells. The expressions
      of JWA, HSP70, HSP27 and HSF1 were determined by Western-blot. RESULTS: The
      inhibitory effect on MCF-7 cells viability induced by H(2)O(2) was shown a dose
      and time-dependent manner and MCF-7 cells proliferation, and was almost
      completely inhibited by the exposure of H(2)O(2) at 1.00 mmol/L for 180 min.
      Hydrogen peroxide treatment of MCF-7 cells caused oxidative stress which up
      regulated the expressions of JWA, HSP70 and heat shock factor 1 (HSF1) in a dose
      dependent manner, and the expression pattern of JWA was very similar to those of
      HSP70 and HSF1 but not to HSP27. CONCLUSION: JWA might enhance intracellular
      defenses against H(2)O(2)-induced oxidative damage in human breast carcinoma
      cells. JWA is determined functioning as an effective environmental responsive
      protein and as a parallel molecule of HSP70 actively participates in the signal
      pathways of oxidative damage which might be regulated by HSF1.

PMID- 16105457
TI  - [Mutational spectra in the tk gene of mouse lymphoma cells induced by
      acrylamide].
AB  - OBJECTIVE: To investigate the mechanism of acrylamide (AA)-induced mutational
      spectra in the tk gene of mouse lymphoma cells. METHODS: L5178Y3.2.7c-tk(+/-)
      cells were treated with AA at different concentrations. Mutational spectra of tk
      locus were analyzed by the mouse lymphoma assay (microtiter procedure), and
      frequency of loss of heterozygosity (LOH) analysis with allele special PCR.
      Subsequently determined the DNA sequence of negative LOH's colonies induced by
      AA. RESULTS: The LOH of mutants derived from AA induction was 78.8%, and showed a
      good dose-response relationship in large colonies. The occurrence of LOH of large
      colonies at lower doses (150 microg/ml and 300 microg/ml) were 25.0% and 33.3%
      respectively which were significantly different from those of control (66.7%),
      and at higher doses (600 microg/ml and 750 microg/ml) were 77.8% and 85.7%. By
      Sequence analysis showed that AA-induced point mutations were mainly base
      substitutions, and most of them were T:G-->G:T transversions. CONCLUSION:
      Functional tk allele gene loss is major mutational event in both spontaneous and
      induced tk mutants. And point mutations were base substitution.

PMID- 16105458
TI  - [Immunological mechanism in development of allergic dermatitis in guinea pig
      induced by trichloroethylene in vitro].
AB  - OBJECTIVE: To investigate the immunological mechanism of allergic dermatitis
      induced by trichloroethylene (TCE). METHODS: The guinea pig model of TCE-induced
      allergic dermatitis was established by Guinea pig Maximization Test. The effects
      of TCE and its metabolites on splenic lymphocytes of TCE-sensitized and non
      sensitized guinea pig were detected by MTT assay. RESULTS: For TCE-sensitized
      guinea pig, the survival rate of lymphocytes cultured with TCE (+S9) was
      significantly higher than that cultured with TCE (-S9) (83.0% +/- 3.4% vs 75.9%
      +/- 7.9%, P < 0.01), while, for normal animals, the survival rate of lymphocytes
      cultured with TCE (+S9) was significantly lower than that cultured with TCE (-S9)
      (63.4% +/- 8.4% vs 77.0% +/- 7.2%, P < 0.01). The survival rate of lymphocytes
      cultured with TCE (+S9) in TCE-sensitized animals was higher than that in normal
      animals (83.0% +/- 3.4% vs 63.4% +/- 8.4%, P < 0.05), but no statistically
      significant difference was found for TCE (-S9) (75.9% +/- 7.9% vs 77.0% +/- 7.2%,
      P > 0.05). CONCLUSION: Cytotoxicity of TCE to normal lymphocytes and
      proliferation of sensitized lymphocytes were enhanced by metabolic activation.
      The metabolites of TCE may act as effective immune hapten to stimulate the
      proliferation of hapten-specific lymphocytes in TCE-sensitized animals.

PMID- 16105459
TI  - [Effect of aluminum chloride on motor activity and species-typical behaviors in
      mice].
AB  - OBJECTIVE: To study the effect of aluminum chloride on motor and species-typical
      behaviors in mice. METHODS: Male ICR mice were administered with drinking double
      distilled water only containing AlCl(3) (10, 50, 300 mg x kg(-1) x d(-1)), and
      control group with drinking double distilled water only for 100 days. Spontaneous
      activity test, grip strength, beam traversal, tightrope task, food hoarding, and
      nest construction were used to study the effect of chloride aluminum on motor and
      species-typical behaviors in mice. RESULTS: The frequencies of spontaneous
      activity in low dose group, medium dose group and high dose group [(81.53 +/-
      8.97), (71.67 +/- 8.37), (66.73 +/- 6.96) times respectively] were lower than
      that in control [(106.46 +/- 8.21) times] (P < 0.01), and were negatively
      correlated with doses (r(s) = -0.42, P < 0.01). Grip strength scores in medium
      dose group (19.19 +/- 1.48) and high dose group (13.36 +/- 1.46) respectively
      were lower than that in control (24.31 +/- 1.43) (P < 0.05, P < 0.01). Food
      hoarding was greater in high dose group [96.10 (90.20-99.00) g] than that in
      control group [84.00 (78.00-90.00) g (P < 0.05)]. The rest of parameters were of
      no statistical significance. CONCLUSION: Subchronic exposure to AlCl(3) in mice
      may diminish motor activity and grip strength, but motor coordination was not
      impaired; alteration in food hoarding suggests damage to hippocampus cell.

PMID- 16105460
TI  - [Bacterial strains and drug-resistance of pneumoconiosis patient with lung
      infection in intensive care unit].

PMID- 16105461
TI  - [Effects of acrylonitrile on the activities of antioxidant enzymes and levels of
      lipid peroxidation in rat testes].
AB  - OBJECTIVE: To explore the mechanism of male reproductive toxicity induced by
      acrylonitrile (ACN). METHODS: Male Sprague-Dawley rats were daily administrated
      ACN by intraperitoneal injection 5 times a week for 13 weeks at the dose of 0,
      7.5, 15.0 and 30.0 mg/kg body weight, respectively. The rats were sacrificed and
      testes were removed at the end of 4, 8, 13 or 15 weeks, respectively. The
      activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and
      glutathione S-transferase (GST) and the levels of glutathione (GSH) and
      malonaldehyde (MDA) were detected in testes. RESULTS: Following ACN treatment of
      4 weeks, the levels of GSH in ACN 15.0 mg/kg and 30.0 mg/kg group were (7.44 +/-
      0.77) mg/g pro and (6.95 +/- 0.77) mg/g pro respectively, and the activity of GSH
      Px was (70.89 +/- 4.01) U/mg pro in 30.0 mg/kg group, all of which were
      significantly higher than the control group (P < 0.05, P < 0.01). After 8 weeks,
      the levels of GSH decreased to (2.50 +/- 0.94) mg/g pro in ACN 30.0 mg/kg group
      (P < 0.01); the activities of SOD increased to (102.08 +/- 16.08) NU/mg pro and
      (113.30 +/- 17.20) NU/mg pro in ACN 15.0 mg/kg and 30.0 mg/kg group (P < 0.01).
      After 13 weeks, the levels of GSH declined in ACN 15.0 mg/kg and 30.0 mg/kg
      group, and the activities of GST decreased in ACN 30.0 mg/kg group, and of GSH-Px
      decreased in both doses group. However, the level of MDA [(0.68 +/- 0.16) nmol/mg
      pro] were significantly higher in 30.0 mg/kg group than that in control group
      [(0.38 +/- 0.12) nmol/mg pro] (P < 0.01). 2 weeks after stopping ACN treatment,
      the level of GSH restored to normal but the levels of MDA or the activity of GSH
      Px in 30.0 mg/kg group were still higher or lower respectively than those of
      control (P < 0.05). CONCLUSION: ACN may impair the balance of antioxidant system,
      thus induce lipid peroxidation damage to rat testes.

PMID- 16105462
TI  - [Effect of carbon disulfide exposure at different phases on the embryonic
      development in mid-pregnancy of female mice].
AB  - OBJECTIVE: To explore the sensitive point of embryotoxicity of carbon disulphide
      on female mice. METHODS: At the phases of follicle developing, implanting and
      post-implantation of blastocyst, female mice were injected intraperitoneally with
      carbon disulphide 631.4 mg/kg per day for three days while controls with plant
      oil. All indexes were detected at the fourteenth day of pregnancy. RESULTS: (1)
      In follicle developing CS(2) exposed group, the weight of embryos fossa [(1.23 +/
      0.36) g was 41% less than that in controls [(2.08 +/- 0.48) g, P = 0.000], and
      in implanting CS(2) exposed group the weight of embryo fossa, and embryos [(1.27
      +/- 0.97) g, and (0.12 +/- 0.09) g respectively] were 39% and 37% less than those
      in controls [(2.08 +/- 0.48), (0.19 +/- 0.06) g, P = 0.068, P = 0.045]; (2) In
      both follicle developing and implanting CS(2) exposed group, the weights of
      uterus and placenta were also less than those in controls (P < 0.01). (3) In post
      implantation CS(2) exposed group, the above parameters were not significantly
      different from those in controls. CONCLUSION: Follicle developing phase as well
      as implanting of blastocyst may be sensitive point for embryotoxicity induced by
      carbon disulphide.

PMID- 16105463
TI  - [Research progress in experimental therapeutic drugs for acute organophosphate
      poisoning].

PMID- 16105464
TI  - [Research progress in related gene of lung cancer caused by radon exposure].

PMID- 16105465
TI  - [Advances in the study on the effect of noise on hearts].

PMID- 16105466
TI  - [The preliminary survey on acute pesticide poisoning in two villages of Shandong
      province].

PMID- 16105467
TI  - [Study on metallic-lactamases of Pseudomonas aeruginosa infection in lower
      respiratory tract of pneumoconiosis coal worker].

PMID- 16105468
TI  - [Dynamic change of serum TNF-alpha in patient with severe acute organic
      phosphorus poisoning complicated by respiratory failure].

PMID- 16105469
TI  - [Clinical observation of HRV in patients with coal worker's pneumoconiosis].

PMID- 16105470
TI  - [DNA damage of human blood lymphocyte induced by styrene and styrene -7, 8
      oxide].

PMID- 16105471
TI  - [The dynamic change of astrocyte reaction after acute omethoate poisoning in
      cat].

PMID- 16105472
TI  - [Preliminary study on quantifying the burden of pneumoconiosis patients with
      disability-adjusted life year].

PMID- 16105473
TI  - Lipoprotein(a): implications for clinical practice.

PMID- 16105475
TI  - New insights in the treatment of dyslipidemia: a focus on cardiovascular event
      reduction and the anti-atherosclerotic effects of atorvastatin.
AB  - The identification and treatment of dyslipidemia is a critical component of
      ongoing efforts to reduce the incidence of atherosclerotic disease in both men
      and women. Several recent large-scale atorvastatin trials provide a plethora of
      information that expands the current body of literature describing the
      pathophysiology of cardiovascular disease and the prevention of acute
      cardiovascular events. These trials demonstrate the benefit of statin therapy in
      a broad variety of patient populations, explore the clinical efficacy of more
      intensive statin regimens, and suggest that the pleiotropic effects of statins
      may contribute to cardiovascular endpoint reduction. In addition, these studies
      have challenged whether current guidelines for low-density lipoprotein
      cholesterol levels provide optimal risk reduction for cardiovascular events.
      Additional studies with atorvastatin are underway to further explore the extent
      to which statins can provide cardiovascular benefits.

PMID- 16105476
TI  - Hepatic high-density lipoprotein receptors: roles in lipoprotein metabolism and
      potential for therapeutic modulation.
AB  - High-density lipoprotein (HDL) plays an important role in protection against
      atherosclerosis. A major part of HDL's antiatherogenic role is through mediating
      reverse cholesterol transport from peripheral cells, such as macrophages and
      other cells in the artery wall, to the liver. Hepatic HDL receptors should,
      therefore, play an important role in either mediating or modulating HDL-dependent
      reverse cholesterol transport. The scavenger receptor class B type I (SR-BI) was
      first identified as a hepatic HDL receptor almost 10 years ago and is well
      characterized at the molecular level. This review highlights recent studies that
      provide insight into the cellular pathways involved in SR-BI-mediated lipid
      transfer between bound lipoproteins and cells, supports a role for this receptor
      in reverse cholesterol transport and protection against experimental
      atherosclerosis in mice, and explores the consequences of sequence variations in
      the gene encoding SR-BI in humans.

PMID- 16105477
TI  - Statins and proteinuria.
AB  - The proteinuria associated with 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors is composed of primarily low-molecular weight proteins that disappear
      rapidly following discontinuation of the statin agent. More importantly, no
      evidence exists of nephrotoxicity or reduced renal function observed with the
      approved clinical dosages of any available statins. Recent clinical studies have
      suggested actual improvement in renal function demonstrated by decreases in
      creatinine concentrations and improvement in estimated glomerular filtration
      rates with both short-term and long-term administration of these agents. The
      progressive fibrosis and renal scarring of chronic kidney disease appears to be
      the end result of increased protein traffic in the proximal renal tubule. Early
      animal and recent clinical studies have suggested that treatment with statin
      agents in established chronic kidney disease can, in fact, provide renoprotection
      over and above that observed with aggressive blood pressure control and the use
      of angiotensin II antagonists.

PMID- 16105478
TI  - Evidence-based management of peripheral vascular disease.
AB  - Peripheral vascular disease (PVD) is very prevalent in the United States and is
      part of a global vascular problem. PVD patients have a heightened inflammatory
      state and are at high risk of death from acute cardiovascular problems rather
      than from progression of PVD. Modifiable risk factors for PVD include smoking,
      hypertension, diabetes, hyperlipidemia, elevated high sensitivity C-reactive
      protein, obesity, and the metabolic syndrome. Symptomatic treatment of
      claudication includes smoking cessation, exercise, cilostazol, statins, and
      revascularization with percutaneous or surgical therapy. Antithrombotic therapy
      with aspirin or clopidogrel is important to reduce cardiovascular events but does
      not affect symptoms of claudication. Patients with rest limb ischemia or
      ulceration should be revascularized to minimize the chance of limb loss.
      Percutaneous revascularization is not without significant complications, however,
      and future research needs to focus on inflammation, thrombosis, and restenosis in
      the PVD patient. Finally, new devices that tackle difficult lesions, drug-eluting
      stents, and pharmacologic agents that reduce global atherosclerosis are on the
      horizon and are likely to become critical components in the management of the PVD
      patient.

PMID- 16105479
TI  - The role of statins in the prevention of ischemic stroke.
AB  - Statin treatment has been demonstrated to diminish the risk for stroke in
      patients with coronary heart disease, hypercholesterolemia, normocholesterolemia,
      in the elderly, and among hypertensive and diabetic patients. Stroke incidence in
      patients on statin treatment has been reduced in all these clinical settings
      involving both primary and secondary prevention but not in patients with previous
      stroke. Two recent meta-analyses confirm this conclusion. The mechanism by which
      statins provide benefit against stroke is likely multifactorial, involving both
      the low-density lipoprotein cholesterol-lowering effect with stabilization of
      vulnerable plaques, and pleiotropic effects such as improvement of endothelial
      function, increased nitric oxide bioavailability, antioxidant properties,
      inhibition of inflammatory responses, immunomodulatory actions, and regulation of
      progenitor cells.

PMID- 16105480
TI  - Impact of thiazolidinedione therapy on atherogenesis.
AB  - Thiazolidinediones (TZDs), which are synthetic ligands for peroxisome
      proliferator activated receptor g (PPARg) activation, have been introduced in
      clinical medicine to improve insulin resistance and glycemic control in patients
      with type 2 diabetes. The metabolic effects of TZDs are mediated by receptor
      dependent activation of the PPARg-retinoid X receptor (RXR) complex and
      subsequent transcriptional activation of target genes. The PPARg1 isoform is also
      expressed in endothelial cells, vascular smooth muscle cells, and
      monocytes/macrophages in the vasculature. TZDs have been shown to have anti
      atherosclerotic effects on these cells in vitro, which appear to be partially
      independent of the PPARg-RXR-mediated transcriptional effects. Direct anti
      atherosclerotic effects of TZDs include increased nitric oxide bioavailability,
      decreased leukocyte/endothelial cell interaction, reduced vascular smooth muscle
      cell migration and proliferation, and cholesterol efflux from macrophages. So
      far, there are no data on the effects of TZDs on cardiovascular events, but
      studies using surrogate markers of vascular disease provide preliminary evidence
      that TZDs delay progression of atherosclerosis in different patient groups. TZDs
      interfere with key processes in atherogenesis and may, therefore, offer
      additional opportunities to improve cardiovascular risk beyond treatment of
      glycemic control in patients with type 2 diabetes.

PMID- 16105481
TI  - Extending the cardiovascular benefits of omega-3 Fatty acids.
AB  - The cardiovascular benefits of omega (n)-3 fatty acids (FA) become clearer with
      each passing year. Although useful in large doses for lowering serum triglyceride
      levels, the primary benefits are likely to arise from smaller, nutritional
      intakes of eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA). Doses of
      less than 1 g/d appear to reduce risk for fatal coronary heart disease events,
      perhaps by stabilizing the myocardium and reducing risk for fatal arrhythmias.
      New evidence points to a possible benefit on atrial fibrillation, particularly in
      the immediate post-cardiac surgery setting. Studies in women with coronary heart
      disease now suggest that plaque progression may be slowed by increased intakes of
      oily fish, even in women with diabetes. The relative importance of the n-6 FA
      linoleic acid (LA), the short-chain n-3 FA alpha linolenic acid (ALA), and the
      long-chain n-3 FAs EPA and DHA is becoming clearer. If intakes of the latter are
      adequate (perhaps over 250 mg/d), then there appears to be little need to consume
      more ALA or less LA.

PMID- 16105482
TI  - Metabolic syndrome: demographic features, etiology, and clinical management.
AB  - The metabolic syndrome, also known as the dysmetabolic syndrome, syndrome X, or
      the insulin resistance syndrome, refers to the clustering of cardiovascular
      disease risk factors that are present in many individuals who are at increased
      risk for cardiovascular events and/or type 2 diabetes. The criteria for metabolic
      syndrome include a combination of categorical and borderline risk factors that
      can be readily measured in clinical practice. Although the Adult Treatment Panel
      III of the National Cholesterol Education Program set the criteria to identify
      cardiovascular risk, the syndrome had already been well recognized in the
      endocrine community as identifying people at risk for diabetes. Recently, the
      International Diabetes Federation proposed a worldwide definition with ethnic
      specific criteria for waist circumference. Therapies targeted to specific
      components of the metabolic syndrome, such as improving glycemic control,
      managing dyslipidemia, and reducing the prothrombotic state, should help to
      minimize cardiovascular risk, particularly if initiated early.

PMID- 16105483
TI  - Lipoprotein(a) and atherosclerosis: new perspectives on the mechanism of action
      of an enigmatic lipoprotein.
AB  - Although elevated plasma concentrations of lipoprotein(a) (Lp(a)) have been
      identified as a risk factor for coronary heart disease, the pathophysiologic and
      physiologic roles of Lp(a) continue to elude basic researchers and clinicians
      alike. Lp(a) is a challenging lipoprotein to study because it has a complex
      structure consisting of a low-density lipoprotein-like moiety to which is
      covalently attached the unique glycoprotein apolipoprotein(a) (apo(a)). Apo(a)
      contains multiply repeated kringle domains that are similar to a sequence found
      in the fibrinolytic proenzyme plasminogen; differing numbers of kringle sequences
      in apo(a) give rise to Lp(a) isoform size heterogeneity. In addition to elevated
      plasma concentrations of Lp(a), apo(a) isoform size has been identified as a risk
      factor for coronary heart disease, although studies addressing this relationship
      have been limited. The similarity of Lp(a) to low-density lipoprotein and
      plasminogen provides an enticing link between the processes of atherosclerosis
      and thrombosis, although a clear demonstration of this association in vivo has
      not been provided. Clearly, Lp(a) is a risk factor for both atherothrombotic and
      purely thrombotic events; a plethora of mechanisms to explain these clinical
      findings has been provided by both in vitro studies as well as animal models for
      Lp(a).

PMID- 16105485
TI  - Editor's commentary: microvascular disease, diabetes, and cardiomyopathy.

PMID- 16105484
TI  - Pleiotropic effects of fibrates.
AB  - Fibrates are a widely used class of hypolipidemic drugs. The effects of fibrates
      are mediated through the activation of the transcription factor peroxisome
      proliferator-activated receptor a (PPARa). Fibrates act to modulate the
      transcription of genes that encode proteins controlling lipid transport and
      metabolism. Fibrates also exert pleiotropic anti-inflammatory effects by down
      regulating expression of genes encoding inflammatory cytokines and acute phase
      response proteins. These combined actions translate into clinical benefit as
      demonstrated by the reduction in cardiovascular morbidity and mortality in
      primary and secondary intervention trials.

PMID- 16105486
TI  - Cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) addresses abnormal left ventricular (LV)
      activation that produces detrimental effects on cardiac systolic and diastolic
      function. CRT improves symptoms and ventricular performance, promotes reverse
      remodeling, and decreases mortality and hospitalization in patients with
      congestive heart failure (CHF). Atrial-synchronized biventricular stimulation
      reverses many of the temporal delays in mechanical activation associated with LV
      dysfunction and conduction system disease. The therapy evolved from anecdotal
      application through surgical implantation of LV pacing leads to transvenous
      delivery of LV pacing leads for use with dedicated CRT devices. The controlled
      clinical trials included specific patient groups, and provided data leading to
      widely adopted indications for the therapy. Current indications exclude the use
      of CRT in patients with permanent atrial fibrillation, although small series
      suggest a benefit of the therapy in these patients. The role of cardiac imaging
      with echocardiography to detect cardiac dyssynchrony promises to improve patient
      selection by not only excluding likely nonresponders, but also extending the
      therapy to those with dyssynchrony in the absence of QRS prolongation. Expanded
      indications under evaluation include the role of CRT in patients with mildly
      symptomatic CHF, mild to moderate LV dysfunction, dyssynchrony in the absence of
      QRS prolongation, and dyssynchrony induced by right ventricular pacing.

PMID- 16105487
TI  - Evaluation of syncope.
AB  - Syncope is not an uncommon condition. The evaluation can be as frustrating as the
      treatment. The role of a detailed history and physical examination cannot be
      underestimated and both remain a cornerstone in the evaluation of syncope. A
      systematic approach may not only lead to correct diagnosis in most cases, but
      also ultimately will be cost effective. This review emphasizes the systematic
      approach for the evaluation of this challenging problem.

PMID- 16105488
TI  - Controversies in pacing: indications and programming.
AB  - This article reviews controversies in cardiac pacing in four areas: methods to
      prevent unnecessary right ventricular pacing and optimal ventricular pacing sites
      in the bradycardia population, pacing for prevention of atrial fibrillation (AF),
      a novel pacing technique for the treatment of heart failure, and pacing for the
      treatment of sleep apnea. Frequent right ventricular pacing has been reported to
      increase the incidence of AF and congestive heart failure. However, many patients
      with pacemakers for bradycardia have intrinsic atrioventricular conduction most
      of the time. Optimal programming of pacemakers and new algorithms designed to
      reduce unnecessary ventricular pacing are discussed. Pacing algorithms for
      prevention of AF have generally been shown to be ineffective. Atrial
      antitachycardia pacing has been shown to reduce the burden of atrial
      tachyarrhythmias in selected patients. Cardiac contractility modulation has
      recently been reported to be a promising new approach to the treatment of heart
      failure. Some pacing techniques may be effective in the treatment of sleep apnea
      but larger, long-term clinical trials are required to demonstrate a significant
      clinical benefit.

PMID- 16105489
TI  - Ablation of ventricular fibrillation and tachycardia.
AB  - Catheter ablation therapy for ventricular tachycardia has evolved over the past
      20 years to become the first-line therapy. This development has been facilitated
      by technology that has allowed better anatomic and electrophysiologic
      correlations. A better understanding of radiofrequency (RF) ablation has led to
      safer and more effective treatments, allowing it to become a potent diagnostic
      and therapeutic tool in clinical cardiac electrophysiology. As more knowledge is
      gained about the mechanisms of arrhythmias through RF ablations, and better
      mapping technology and more effective methods for energy delivery become
      available, catheter ablation will become relevant for an increasing number of
      arrhythmias. This article addresses advances and applications of RF ablation to
      the treatment of ventricular arrhythmias in a variety of heart diseases.

PMID- 16105491
TI  - Anticoagulation: new challenges, old drugs.
AB  - Effective atrial fibrillation (AF) management requires attention to adequate rate
      control, consideration for the need to maintain sinus rhythm, and deliberation
      regarding proper anticoagulation to prevent thromboemboli. When properly used,
      warfarin anticoagulation in patients with AF at high risk for stroke reduces
      stroke incidence markedly. Unfortunately, proper anticoagulation with warfarin is
      not easy. An anticoagulant drug for which there are few interactions with other
      drugs, food, or supplements; for which there can be uniform dosing; for which
      routine International Normalized Ratio monitoring is not required; and for which
      there is a lower risk for bleeding, will gain widespread and rapid acceptance. In
      two large randomized trials comparing fixed-dose ximelagatran with warfarin in
      noninferiority studies, ximelagatran appears to be as effective at preventing
      stroke and thromboembolic events as warfarin (based on intention-to-treat
      analysis) and with similar, if not better, long-term risk.

PMID- 16105490
TI  - Sudden cardiac death without structural heart disease: update on the long QT and
      Brugada syndromes.
AB  - The long QT syndrome (LQTS) and the Brugada syndrome (BrS) are the most common
      genetic causes of malignant ventricular arrhythmias and sudden cardiac death in
      young patients with normal cardiac morphology. To date, more than 250 different
      mutations in seven genes have been identified as causing LQTS, whereas the only
      gene identified to be linked to BrS is SCN5A. In both syndromes, gene-specific
      mutations have been shown to be associated with specific phenotypic expressions.
      Risk stratification in LQTS and BrS is based mainly upon a constellation of
      electrocardiographic findings and a history of prior symptoms. In patients
      identified as high risk for arrhythmic mortality, the implantable cardioverter
      defibrillator is the most effective treatment and has been shown to provide near
      complete protection during long-term follow-up.

PMID- 16105492
TI  - Palpitations: a proper evaluation and approach to effective medical therapy.
AB  - Palpitations are a common complaint seen in the outpatient setting and the vast
      majority are benign, although they are occasionally a manifestation of
      potentially life-threatening conditions. We offer a step-wise guide to the
      evaluation and management of these patients with the primary goal to identify
      patients at highest risk for serious arrhythmias. We offer a brief overview of
      effective management of the varied causes of palpitations.

PMID- 16105493
TI  - Nonsustained ventricular tachycardia in dilated cardiomyopathy.
AB  - In patients with structural heart disease, ventricular arrhythmias are associated
      with an increased risk of overall mortality and sudden cardiac death (SCD).
      Nonsustained ventricular tachycardia (NSVT) is common in patients with dilated
      cardiomyopathy of both ischemic and nonischemic origin. Recent studies suggest
      that NSVT may be a marker, but not a significant predictor, of mortality and SCD
      in that suppression of NSVT in these patients using antiarrhythmic drugs is of
      questionable benefit. Additionally, indications for implantable cardioverter
      defibrillator implantation do not include NSVT. This article focuses on the
      prognostic significance and treatment of patients with NSVT and ischemic or
      nonischemic dilated cardiomyopathy.

PMID- 16105494
TI  - Approach to antiarrhythmic therapy in patients with ICDs and frequent
      activations.
AB  - Patients with an implantable defibrillator may require concomitant antiarrhythmic
      drug therapy to reduce therapy from the device, especially shocks from the
      device. New evidence suggests that amiodarone, in combination with b-blockade, is
      the most effective treatment to reduce the frequency of defibrillator therapies,
      but sotalol and azimilide have also been shown to be effective. Electrical storm
      is a serious condition that occurs in 20% of patients living with a
      defibrillator, and its management requires a complex approach to the patient.

PMID- 16105495
TI  - Prophylaxis and management of postoperative atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia seen after cardiac
      surgery. It is associated with prolongation of hospital stay, postoperative
      complications, stroke, mortality, and increased hospital cost. Several prevention
      strategies have been proven effective in reducing postoperative AF; in addition,
      active prevention of postoperative AF is associated with a decrease in the length
      of hospital stay and a reduction trend in hospital costs. In patients with
      postoperative AF, restoration and maintenance of sinus rhythm and rate control
      are adequate treatment alternatives in the majority of cases. In severely
      symptomatic or hemodynamically compromised patients urgent cardioversion is
      needed. Adequate oral anticoagulation may be indicated for a limited period of
      time.

PMID- 16105496
TI  - Atrial fibrillation: how to approach rate control.
AB  - The optimal management of atrial fibrillation is of considerable clinical
      importance, and with the recent publication of four studies suggesting the
      equivalence of rate and rhythm control strategies, new attention has been focused
      on rate control. Reasons for rate control include reduction of symptoms and the
      prevention of tachycardia-mediated cardiomyopathy; yet, evidence-based
      definitions of optimal rate control are lacking. This article examines an
      approach to rate control that includes serial assessment of heart rate and
      symptoms, both at rest and with exertion, and the use of therapy tailored to the
      individual and modified over time (as no single therapy demonstrates clear
      superiority). Often, multidrug regimens including digoxin and a calcium channel
      blocker or beta-blocker are required, and in a minority of patients
      atrioventricular nodal ablation and pacing are necessary. Several novel therapies
      currently under development are also discussed.

PMID- 16105497
TI  - Outcomes of the MS-30 cemented femoral stem.
AB  - The MS-30 (Morscher-Spotorno) cemented femoral stem is a straight, three
      dimensionally tapered, collarless implant for cemented fixation in total hip
      replacement, manufactured from a FeCrNiMnMoNb-alloy. This paper documents the
      review of 4 original follow-ups performed at four orthopaedic hospitals: three at
      the author's institution (Basel/Switzerland 2, Pietra Ligure/Italy 1), and one at
      the University Orthopaedic Hospital of Heidelberg/ Germany. A total of 911 hips
      in 867 patients have been provided with the MS-30 stem. All stems were fixed with
      Palacos bone cement, the great majority with antibiotic (Gentamicine) loaded
      cement. The mean observation time was 10.2, 5.6, 10.2 and 6.5 years. One hundred
      and sixty-four hips were lost due to patients death, 121 patients were unable to
      come to the follow-up check. Ten patients only were lost to follow-up. The total
      number of hips with a clinical radiological follow-up was 597. The clinical and
      radiological assessment was in accordance with the International Documentation
      and Evaluation System (IDES) forms from the Institute of Documentation of the
      M.E. Muller Foundation in Berne/Switzerland. RESULTS The overall survivorship in
      the four follow-ups were 100% after 10 years, 98.4% and 99.2% after 5.5.years,
      98.5% after 10 years and finally 96.1% after 6.5 years. The respective
      percentages of survival for aseptic loosening were 100%, 99.2%, 100%, 98.5% and
      98.8%. CONCLUSION According to the NIH (National Institute of Health, United
      Kingdom) a survival rate of 95% regarding aseptic loosening justifies or even
      recommends further clinical use of the respective endoprosthesis system.

PMID- 16105498
TI  - [Arthroscopic stabilization of the fractured intercondylar eminence].
AB  - PURPOSE OF THE STUDY: The authors present the results of arthroscopic reduction
      of a displaced fracture of the intercondylar eminence and stabilization of the
      fracture with a tension band wire and absorbable, double PDS sutures. MATERIAL:
      In the years 1998 to 2002, a fracture of the intercondylar eminence was
      arthroscopically diagnosed in 34 patients, 21 women and 13 men in the age range
      of 17 to 46 years. Five patients had type I fracture, 13 had type II fracture and
      16 had type III fracture, as classified by the Meyers and McKeever system.
      Arthroscopic stabilization was used for all type II and type III fractures in a
      total of 29 patients. Double PDS sutures no. 1 were always applied. One double
      PDS loop was used in eight patients and, in the rest, two or three double PDS
      loops were employed. METHODS: PDS no. 1 sutures were inserted, by means of wire
      loops, through bone tunnels. These were drilled with 2-mm Kirschner's wires,
      using an anterior cruciate ligament (ACL) reamer, medial to the tibial
      tuberosity. Double PDS sutures were applied to the distal portion of the ACL,
      which permits good stabilization even in comminuted fractures of the eminence.
      The strength of a double PDS loop is sufficient and facilitates speedy recovery.
      Before terminating surgery it is necessary to check joint mobility and fixation
      stability. Only good stability allows for early mobilization of the joint. The
      postoperative treatment involved immobilization of the knee joint with a rigid
      brace in a semi-flexed position at 20 degrees for 6 weeks. However, from the
      second postoperative day, the brace was removed during targeted rehabilitation.
      Exercise on a continuous passive motion device, strengthening of the thigh
      muscles, patellar mobilization, walking with the use of crutches, while wearing
      the brace, with partial weight bearing until pain were practised. A treadmill
      without loading was used from the fifth postoperative week. RESULTS: Twenty-nine
      patients in whom stabilization with PDS sutures was used were evaluated. Of them
      26 were completely free from any complaints and fully healed, always without
      findings of displacement on X-ray. In one patient, a fragment of the comminuted
      fracture was loosened and interfered with full extension. It was removed by
      arthroscopy and full recovery without consequences ensued. One patient underwent
      repeat surgery for hematoma in the wound; after wound healing and rehabilitation,
      he achieved a full range of motion. One patient showed signs of fibrosis of
      Hoffa's fat pad. All patients returned to the style of life as before injury. At
      follow-up of 1 to 4 years, Lysholm scores were excellent in 23 patients, very
      good in four patients, satisfactory in one patient (repeat surgery) and one
      patient was not examined. DISCUSSION: Fracture of the intercondylar eminence is
      caused by a mechanism similar to that causing rupture of the anterior cruciate
      ligament but, in addition, the margin of the intercondylar fossa is pressed
      against the eminence which breaks off. Displaced fractures (types II and III
      according to the Meyers and McKeever classification) are indicated for surgical
      stabilization. Fixation of the fractured eminence by means of absorbable material
      is sufficient, and insertion of metal material and its subsequent removal thus
      can be avoided. Arthroscopic inspection permits exact reduction; this procedure
      is minimally invasive. CONCLUSIONS: Arthroscopic stabilization of a fractured
      eminence by means of PDS sutures is a gentle surgical procedure that provides
      good mechanical support, facilitates early rehabilitation and achieves good
      outcomes. The use of absorbable sutures allows us to avoid further surgery in
      order to remove fixation material.

PMID- 16105499
TI  - [Monteggia's lesion in childhood--proposal for a new classification system].
AB  - PURPOSE OF THE STUDY: The former classification systems have failed to provide an
      exact characterization of Monteggia's lesions (ML) in a growing skeleton. We
      studied the stability of both ulnar fracture and injury to the radio-humero-ulnar
      joint and our clinical findings fully warrant the proposal of a new
      classification system. MATERIAL: We carried out a retrospective study of 76
      children, aged 2 to 15 years, treated for Monteggia's lesion in our department
      during 12 years, from 1990 till 2001. METHODS: X-ray images of all injured limbs
      were evaluated and each injury was categorized as stable, potentially unstable or
      unstable. This concerned both ulnar fractures and lesions affecting the radio
      humero-ulnar joint. An assessment of the therapeutic method used was also
      included. RESULTS: The final assessment of each injury involved the category of
      ulnar fracture and the category of radio-humero-ulnar joint lesion and produced
      three ML types, namely, stable, potentially unstable and unstable types. A stable
      ML type was found in 30 (39.5 %) patients and, in most of them, conservative
      treatment was sufficient. Osteosynthesis was required in only 6.7 % of the cases.
      A potentially unstable ML type was recorded in 27 (35.3 %) patients. Fifteen of
      these (55.6 %) underwent osteosynthesis because conservative treatment had
      failed. An unstable ML type was diagnosed in 19 (25 %) children and nearly all of
      them (89.5 %) had to undergo osteosynthesis. DISCUSSION: The previous
      classification systems have been based on either anatomical aspects (direction of
      ulnar fragment displacement and proximal radius dislocation) or the type of ulnar
      fracture. In our view the characterization of each ML type in children involves
      the stability of ulnar fraction as well as the stability of injury to the radio
      humero-ulnar joint. CONCLUSIONS: Our classification allows us to predict the
      stability of each Monteggia's lesion and to choose an appropriate approach to its
      treatment.

PMID- 16105500
TI  - [Video-assisted tenotomy of the triceps muscle of the calf in cerebral palsy
      patients].
AB  - PURPOSE OF THE STUDY: The aim of the study was to demonstrate the outcomes of
      video-assisted tenotomy of the gastrocnemius and soleus muscles in children with
      the spastic form of cerebral palsy. MATERIAL: In the period from September 2003
      to March 2004, 18 lower extremities in 14 patients were operated on.A set for
      endoscopic plastic surgery with a 4-mm trocar was used. Aponeurotomy was carried
      out with a scalpel no. 11 or arthroscopic scissors. The treated limb was
      immobilized in plaster cast for 6 weeks. METHODS The inclusion criteria were: an
      equinus gait free from a valgus or a varus deviation, preferably unilateral, and
      the age range between 4 and 10 years. The patients were examined before surgery
      and followed up at 3-month intervals. RESULTS: In 16 out of 18 treated
      extremities, simple aponeurotomy of the gastrocnemius and soleus muscles was
      sufficient to achieve 20 degrees dorsiflexion. In two cases it was necessary to
      complete the procedure at the same stage by video-assisted sliding double-point
      tenotomy of the Achilles tendon. The short-term follow-up did not reveal
      complications such as failure of wound healing or neurological or vascular
      disturbance. DISCUSSION: The international literature data show that this method
      has largely been developed on cadavers. Much attention has been given to
      potential injury to the sural nerve. However, the ultimate goal of this
      operation, i. e., sufficient correction, should be regarded as a much more
      important factor. In older children, simple aponeurotomy may not achieve this
      objective and therefore the authors developed a procedure combining video
      assisted aponeurotomy with sliding double-point tenotomy of the Achilles tendon.
      CONCLUSIONS: Video-assisted tenotomy of the gastrocnemius and soleus muscles
      proved a fully effective method in our group evaluated at short-term follow-up.

PMID- 16105501
TI  - [An occult acetabular fracture revealed by magnetic resonance imaging].
AB  - The authors describe the case of a 35-year-old man with an injury to the left hip
      joint. When examined at the surgical ward, the patient complained of pain and
      restricted motion of the left hip. No traumatic changes in the left hip joint
      were revealed on X-ray and CT examination. When checked-up 13 days later, the
      patients still complained of persistent pain and restricted movement. Because of
      the discrepancy between the results of X-ray and clinical examinations, magnetic
      resonance imaging was recommended. This revealed an infraction of the roof of the
      acetabulum without trauma to the soft joint tissues and adjacent muscles. A
      retrospective analysis of the X-ray and CT examination data showed an infraction
      of the acetabular roof on CT scans. The authors emphasize the role of non
      invasive magnetic resonance imaging in the diagnosis of occult fractures.

PMID- 16105502
TI  - [Bone and joint involvement in human immunodeficiency virus infection].
AB  - The bone and joint complications of HIV infection continue to be reported. Some,
      in particular the metabolic bone disorders have become more prominent in the era
      of potent antiretroviral therapy. However, the epidemiology and the
      pathophysiology of these disorders as well as their relationship to the HIV
      infection itself, to the duration of illness, or to antiretroviral therapy remain
      largely undefined. This article attempts to provide a broad overview of the
      complications of HIV and its treatment involving the bone and joints.

PMID- 16105503
TI  - [General principles of infection treatment in joint replacements].
AB  - The treatment of infection in joint replacements, which is a complex issue, is
      justly considered to be one of the most expensive orthopedic procedures. The
      choice of treatment is determined by a number of criteria that are based on exact
      patients' history and their clinical, imaging and laboratory data. The management
      of infection reflects the development in the field of arthroplasty. In the past,
      the therapy was rather simple, involving removal of the implant, eradication of
      the infection and simple anatomical intervention in order to make the extremity
      useful for the patient, often at the cost of many concessions. At present, with
      rapid advancements of alloplasty, patients' requirements for joint motion are
      increasing and the ultimate goal is a new and fully functioning joint prosthesis.
      This treatment is based on early diagnosis as well as early surgical
      intervention. Antibiotic therapy alone is indicated only in Coventry's type I
      infection, when positive results of bacterial cultivation are known only after
      the surgical procedure. A 6-week antibiotic course is administered according to
      the sensitivity of the isolated bacterial strain. Although treatment solely with
      antibiotics is preferred by the patients, its long-term outcomes, with the
      exception of the indication mentioned above, are completely ineffective. Surgical
      inspection and lavage without implant removal and a subsequent antibiotic course
      are indicated in type II infection. The procedure involves thorough debridement
      and replacement of the articulating component, followed by conventional lavage
      irrigation. One-stage reimplantation requires implant removal, debridement and
      insertion of a new implant. This is indicated in patients with type III and type
      IV alloplasty infection by Gram-positive sensitive bacteria that do not produce a
      glycocalyx layer and in patients in whom the bone bed is without major defects.
      The method of choice is an implant fixed with antibiotic- loaded cement.One-stage
      reimplantation is associated with a shorter absence from work, lower costs and
      better comfort for the patient. Two-stage reimplantation is generally preferred.
      It is indicated in type III and type IV alloplasty infections caused by resistant
      or polymicrobial flora or by glycocalyx-producing bacteria, and in patients with
      large defects of the bone bed. The first stage includes removal of all prosthetic
      components, thorough debridement and insertion of a cement, conventional or
      articulating, spacer. Lavage irrigation follows. Based on clinical and laboratory
      findings, the second stage procedure is carried out after 6 to 12 weeks and a
      new, usually cementless implant is inserted and defects are repaired, if present.
      In the treatment of infected alloplasty, a cement spacer has two roles; it
      provides stability for the joint region after removal of the replacement and, by
      releasing antibiotics, it prevents the spacer from colonization by bacteria. The
      cement spacer can be prepared in several ways. The modification preferred by the
      authors consists only of antibiotic-loaded bone cement moulded in such a way that
      it can fulfill its stabilizing function and, in hip joints, partially also its
      locomotor function. Other options include a commercially-produced cement spacer,
      which has the shape of a cervicocapital prosthesis and is merely placed in the
      bone bed, or the PROSTALAC system. A three-stage reimplantation procedure is
      suitable for treatment of extensive bone defects in which the use of a large
      amount of morselized homograft can be anticipated. The bone bed created from
      homografts is allowed to incorporate for about 6 months and, in most cases, a
      cementless implant is subsequently inserted.

PMID- 16105504
TI  - [Molecular markers of osteoarthritis].
AB  - Osteoarthritis (OA) is a chronic joint disorder characterized by articular
      cartilage destruction, subchondral bone alteration and variable synovial
      inflammation. Diagnosis of the disease, the progression of joint damage, and the
      monitoring of effect of structure modifying treatment, are still based on less
      sensitive evaluation of clinical and radiological findings. Molecular markers
      represent a new field of interest to serve as surrogate indicators for OA
      evaluation. These markers may provide direct information about the alteration of
      joint tissue metabolism and related bone and cartilage turnover and/or local
      inflammation. Currently available molecular markers or their combinations may
      provide a tool for early onset detection of OA. Additionally, these markers may
      aid in the identification of patients at high risk of rapid joint destruction,
      and the prediction of OA progression. Molecular markers may also play a very
      important role in the monitoring of the responsiveness to OA treatment.

PMID- 16105505
TI  - Imaging dose-dependent pharmacokinetics of an RGD-fluorescent dye conjugate
      targeted to alpha v beta 3 receptor expressed in Kaposi's sarcoma.
AB  - Dynamic fluorescence images were obtained from xenografts bearing a subcutaneous
      human Kaposi's sarcoma (KS1767) immediately following the intravenous injection
      of an integrin-receptor targeting Cy5.5-c(KRGDf) at a dose ranging from 0.75 to 6
      nmol/mouse. The fluorescence images were acquired using an intensified charge
      coupled device system and were analyzed with a three-compartment pharmacokinetic
      (PK) model to determine uptake parameters in the tumor and normal tissue regions
      of interest as a function of administered dose. Our results show that the uptake
      of Cy5.5-c(KRGDf) in tumor regions were: (i) significantly greater than the
      contralateral normal tissue regions; (ii) linearly increased with dose of Cy5.5
      c(KRGDf) up to 1.5 nmol/mouse; and (iii) blocked by preinjection of c(KRGDf).
      Above doses of 1.5 nmol/mouse, the uptake no longer increased with dose,
      suggesting integrin receptor saturation. In normal tissues, the PK uptake
      parameters were not influenced by Cy5.5-c(KRGDf) dose nor by the
      preadministration of c(KRGDf).

PMID- 16105506
TI  - Visualizing drug efficacy in vivo.
AB  - Many enzymes are therapeutic targets for drug discovery, whereas other enzymes
      are important for understanding drug metabolism and pharmacokinetics during
      compound testing in animals. Testing of drug efficacy and metabolism in an animal
      model requires the measurement of disease endpoints as well as assays of enzyme
      activity in specific tissues at selected time points during treatment. This
      requires the removal of tissue and biochemical assays. Techniques to
      noninvasively assess drug effects on enzyme activity using imaging technology
      would facilitate understanding of drug efficacy, pharmacokinetics, and drug
      metabolism. Using a commercially available cytochrome P-450 3A substrate whose
      oxidized product is a luciferase substrate, we show for the first time that
      cytochrome P-450 enzyme activity can be measured in vivo in real time by
      bioluminescent imaging. This imaging approach could be applicable to study drug
      effects on therapeutic target enzymes, as well as drug metabolism enzymes.

PMID- 16105507
TI  - Meeting report: high-throughput technologies for in vivo imaging agents.
AB  - Combinatorial chemistry and high-throughput screening have become standard tools
      for discovering new drug candidates with suitable pharmacological properties.
      Now, those same technologies are starting to be applied to the problem of
      discovering novel in vivo imaging agents. Important differences in the biological
      and pharmacological properties needed for imaging agents, compared to those for a
      therapeutic agent, require new screening methods that emphasize those
      characteristics, such as optimized residence time and tissue specificity, that
      make for a good imaging agent candidate.

PMID- 16105508
TI  - Improved stem cell MR detectability in animal models by modification of the
      inhalation gas.
AB  - In vivo monitoring of cells labeled with paramagnetic iron oxide particles by
      magnetic resonance imaging (MRI) is complicated by intrinsic contrast of blood
      vessels. Distinction between T2* effects caused by blood vessels from those
      caused by labeled cells was so far only possible after carefully following the
      location of hypointense regions through subsequent slices of T2*-weighted 3-D MRI
      datasets, a procedure that is time consuming and not always reliable in the case
      of smaller blood vessels. Here, we demonstrate that the modification of the
      inhalation gas mixture from the routinely used composition 35% O2 and 65% N2O to
      a mixture containing 95% O2 and 5% CO2 results in a contrast suppression of most
      small blood vessels and reduces the intrinsic T2* effect of large vessels
      dramatically in an animal model. This change in protocol of physiological
      conditions was well tolerated by all studied animals, even over prolonged
      experimental times. The changed inhalation gas mixture thus provides a more
      reliable identification method for small clusters of iron oxide labeled cells in
      vivo.

PMID- 16105509
TI  - 4-D micro-CT of the mouse heart.
AB  - PURPOSE: Demonstrate noninvasive imaging methods for in vivo characterization of
      cardiac structure and function in mice using a micro-CT system that provides high
      photon fluence rate and integrated motion control. MATERIALS AND METHODS:
      Simultaneous cardiac- and respiratory-gated micro-CT was performed in C57BL/6
      mice during constant intravenous infusion of a conventional iodinated contrast
      agent (Isovue-370), and after a single intravenous injection of a blood pool
      contrast agent (Fenestra VC). Multiple phases of the cardiac cycle were
      reconstructed with contrast to noise and spatial resolution sufficient for
      quantitative assessment of cardiac function. RESULTS: Contrast enhancement with
      Isovue-370 increased over time with a maximum of approximately 500 HU (aorta) and
      900 HU (kidney cortex). Fenestra VC provided more constant enhancement over 3 hr,
      with maximum enhancement of approximately 620 HU (aorta) and approximately 90 HU
      (kidney cortex). The maximum enhancement difference between blood and myocardium
      in the heart was approximately 250 HU for Isovue-370 and approximately 500 HU for
      Fenestra VC. In mice with Fenestra VC, volumetric measurements of the left
      ventricle were performed and cardiac function was estimated by ejection fraction,
      stroke volume, and cardiac output. CONCLUSION: Image quality with Fenestra VC was
      sufficient for morphological and functional studies required for a standardized
      method of cardiac phenotyping of the mouse.

PMID- 16105510
TI  - Development of a single detector ring micro crystal element scanner: QuickPET II.
AB  - This article describes a single ring version of the micro crystal element scanner
      (MiCES) and investigation of its spatial resolution imaging characteristics for
      mouse positron emission tomography (PET) imaging. This single ring version of the
      MiCES system, referred to as QuickPET II, consists of 18 MiCE detector modules
      mounted as a single ring in a vertical gantry. The system has a 5.76-cm
      transverse field of view and a 1.98-cm axial field of view. In addition to the
      scanner and data acquisition system, we have developed an iterative
      reconstruction that includes a model of the system's detector response function.
      Evaluation images of line sources and mice have been acquired. Using filtered
      backprojection, the resolution for a reconstructed line source has been measured
      at 1.2 mm full width at half maximum. F-18-2-fluoro-2-deoxyglucose mouse PET
      images are provided. The result shows that QuickPET II has the imaging
      characteristics to support high-resolution, static mouse PET studies using 18-F
      labeled compounds.

PMID- 16105511
TI  - Noninvasive monitoring of pneumococcal meningitis and evaluation of treatment
      efficacy in an experimental mouse model.
AB  - Noninvasive real-time in vivo bioluminescent imaging was used to assess the
      spread of Streptococcus pneumoniae throughout the spinal cord and brain during
      the acute stages of bacterial meningitis. A mouse model was established by lumbar
      (LP) or intracisternal (IC) injection of bioluminescent S. pneumoniae into the
      subarachnoid space. Bacteria replicated initially at the site of inoculation and
      spread progressively from the spinal cord to the brain or from the brain down to
      the cervical part of the spinal column and to the lower vertebral levels. After
      24 hr, animals showed strong bioluminescent signals throughout the spinal canal,
      indicating acute meningitis of the intracranial and intraspinal meninges. A
      decline in bacterial cell viability, as judged by a reduction in the
      bioluminescent signal, was observed over time in animals treated with
      ceftriaxone, but not in untreated groups. Mice treated with the antibiotic
      survived infection, whereas all mice in untreated groups became moribund, first
      in the IC group then in the LP group. No untreated animal survived beyond 48 hr
      after induction of infection. Colony counts of infected cerebrospinal fluid (CSF)
      correlated positively with bioluminescent signals. This methodology is especially
      appealing because it allows detecting infected mice as early as 3 hr after
      inoculation, provide temporal, sequential, and spatial distribution of bacteria
      within the brain and spinal cord throughout the entire disease process and the
      rapid monitoring of treatment efficacy in a nondestructive manner. Moreover, it
      avoids the need to sacrifice the animals for CSF sampling and the potential
      manipulative damage that can occur with other conventional methods.

PMID- 16105512
TI  - Glucose metabolism of human prostate cancer mouse xenografts.
AB  - We hypothesized that the glucose metabolism of prostate cancer is modulated by
      androgen. We performed in vivo biodistribution and imaging studies of [F-18]
      fluorodeoxyglucose (FDG) accumulation in androgen-sensitive (CWR-22) and androgen
      independent (PC-3) human prostate cancer xenografts implanted in castrated and
      noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best
      approximated by an exponential function (tumor size in mm3 = 14.913 e(0.1086 x
      days), R2 = .96, n = 5). The growth pattern of the PC-3 tumor was best
      approximated by a quadratic function (tumor size in mm3 = 0.3511 x days2 + 49.418
      x day - 753.33, R2 = .96, n = 3). The FDG accumulation in the CWR-22 tumor
      implanted in the castrated mice was significantly lower, by an average of 55%, in
      comparison to that implanted in the noncastrated host (1.27 vs. 2.83,
      respectively, p < .05). The 3-week maximal standardized uptake value (SUVmax) was
      0.99 +/- 0.43 (mean +/- SD) for CWR-22 and 1.21 +/- 0.32 for PC-3, respectively.
      The 5-week SUVmax was 1.22 +/- 0.08 for CWR-22 and 1.35 +/- 0.17 for PC-3,
      respectively. The background muscle SUVmax was 0.53 +/- 0.11. Glucose metabolism
      was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18%)
      and the 5-week (by 9.6%) micro-PET imaging sessions. Our results support the
      notions that FDG PET may be useful in the imaging evaluation of response to
      androgen ablation therapy and in the early prediction of hormone refractoriness
      in men with metastatic prostate cancer.

PMID- 16105513
TI  - hNIS-IRES-eGFP dual reporter gene imaging.
AB  - The human and rodent sodium iodide symporters (NIS) have recently been cloned and
      are being investigated as potential therapeutic and reporter genes. We have
      extended this effort by constructing an internal ribosomal entry site (IRES)
      linked human NIS (hNIS)-enhanced green fluorescent protein (eGFP) hybrid reporter
      gene for both nuclear and optical imaging. A self-inactivating retroviral vector,
      termed pQCNIG, containing hNIS-IRES-eGFP dual reporter gene, driven by a
      constitutive CMV promoter, was constructed and used to generate RG2-pQCNIG cells
      and RG2-pQCNIG tumors. 131I-iodide and 99mTcO4-pertechnetate accumulation studies
      plus fluorescence microscopy and intensity assays were performed in vitro, and
      gamma camera imaging studies in RG2-pQCNIG and RG2 tumor-bearing athymic rats
      were performed. RG2-pQCNIG cells expressed high levels of hNIS protein and showed
      high intensity of eGFP fluorescence compared with RG2 wild-type cells. RG2-pQCNIG
      cells accumulated Na131I and 99mTcO4- to a 50:1 and a 170:1 tissue/medium ratio
      at 10 min, compared with 0.8:1.2 tissue/medium ratio in wild-type RG2 cells. A
      significant correlation between radiotracer accumulation and eGFP fluorescence
      intensity was demonstrated. RG2-pQCNIG and RG2 tumors were readily differentiated
      by in vivo gamma camera imaging; radiotracer uptake increased in RG2-pQCNIG but
      declined in RG2 tumors over the 50-min imaging period. Stomach and thyroid were
      the major organs of radionuclide accumulation. The IRES-linked hNIS-eGFP dual
      reporter gene is functional and stable in transduced RG2-pQCNIG cells. Optical
      and nuclear imaging of tumors produced from these cell lines provides the
      opportunity to monitor tumor growth and response to therapy. These studies
      indicate the potential for a wider application of hNIS reporter imaging and
      translation into patient studies using radioisotopes that are currently available
      for human use for both SPECT and PET imaging.

PMID- 16105514
TI  - Brief communication of the Residency Review Committee-Surgery (RRC-S) on
      residents' surgical volume in general surgery.
AB  - BACKGROUND: The Residency Review Committee-Surgery (RRC--S), 1 of 10 surgical
      specialties of the Accreditation Council for Graduate Medical Education (ACGME)
      has monitored the surgical volume of all general surgical residents closely. As a
      consequence of the reduction of duty hours with the limitation of an 80-hour work
      week (averaged over 4 weeks), we were interested in the impact of these
      restrictions on surgical (volume) experience since its first year of
      implementation (2003--2004). Therefore, we evaluated the surgical volume of
      general surgical services since the implementation of the ACGME duty-hour
      restrictions and compared this volume with that of previous years without these
      duty limits. METHODS: The Biostatistical Management Section of the ACGME
      implemented prospective analysis of categorized data for total surgical
      procedures and Chief Resident cases. The study interval included all resident
      surgical procedures completed from 1997 to 2004. We were interested particularly
      in evaluating trends and outcomes after the first year of successful full
      compliance of the 80-hour work week. Specific evaluations included the impact on
      surgical programs for total major procedures and Chief Resident cases requisite
      for application to the American Board of Surgery. RESULTS: The average number of
      total major procedures for both resident and program averages were noted to
      increase steadily through the academic years of evaluation (1997--2001). A sharp
      decrease was evident in the total major procedures for the academic year 2001-
      2002 that relates to a correction of the biostatistical database implemented by
      the ACGME to correct a system conversion that began in the academic year 2001-
      2002. Despite significant changes to the system data mappings, beginning in the
      academic year 2001, this reduction is explained by the total counted surgeries as
      major that were eliminated in a revised counting methodology. It was evident on
      evaluation of the average (of averages) for major surgical procedures per
      resident (per program) in academic years 1997 to 2004 that the number of
      procedures was not statistically different in the academic years evaluated when
      compared with the year for implementation of duty-hour standards (2003--2004).
      Data analysis further indicates that the average procedures (per resident)
      performed as Chief Resident in general surgery remained stable from 1997 to 2004;
      the use of tiered t tests comparing Chief Resident averages (per program) for the
      academic years 2002--2003 versus 2003--2004 indicated that data remained
      consistent and confirmed no statistical variance in volumes during this interval
      (P=0.43). Because some general surgery programs have exceptions for duty-hour
      requirements (n=15) to allow an 88-hour week averaged over 4 weeks, these
      differences were of interest to evaluate programs with and without these duty
      hour exceptions. Preliminary data with these limited parameters of evaluation
      suggest no detrimental outcomes related to the duty-hour restrictions for total
      major procedures per resident or for surgical procedures as Chief Residents for
      programs with and without these approved exceptions. CONCLUSIONS: RRCs that
      evaluate general surgery and surgical specialties have responded aggressively and
      professionally to implement the duty-hour standards per the ACGME. This brief
      report should be considered an interim communication to evaluate the surgical
      experience impact for programs currently under the restriction of duty-hour
      limits. The data provided in the first year of evaluation since the
      implementation of the 80-hour work-week restriction policy suggest that there has
      been no significant change in the overall surgical experience for major
      procedures (per resident), nor has there been a negative impact on Chief Resident
      surgical experience. A continuum of the prospective evaluation process is
      required by the RRC-S and other surgical specialties to ensure that requisite
      surgical volume is maintained throughout the entire 5 years of clinical surgery.

PMID- 16105515
TI  - How much time do surgical residents need to learn operative surgery?
AB  - BACKGROUND: We calculated the time a resident spent to acquire the average
      operative experience before mandated duty hours, to generate a standard for
      curriculum redesign. METHODS: By using data from 2002 to 2003 furnished by the
      Residency Review Committee for Surgery, and the operation times of attending
      surgeons in a hospital consortium, the time devoted to operative surgery over 5
      years of training were calculated. RESULTS: An average of 2753 hours or 14.3% of
      19,200 hours (5 years of 80-hour work weeks) were spent as a chief surgeon, 272
      hours as an assistant, and another 938 hours for immediate preoperative and
      postoperative attendance. The average total time for operative training was 3963
      hours or 20.6% of 5 years of 80-hour weeks (16.5 h/wk). CONCLUSIONS: The database
      is useful for redesigning the surgical curriculum for the mandated duty hours. It
      also may be used to determine rapidly if a program currently is providing
      sufficient time for operative surgery.

PMID- 16105516
TI  - Learning to operate in a restricted duty hours environment.

PMID- 16105517
TI  - A surgeon who CARES can be safer.
AB  - The characteristics of a high-reliability organization are reviewed. Examples of
      how these characteristics relate to patient safety in surgical practice are
      illustrated by vignettes. The characteristics discussed include commitment to
      safety demonstrated to others by the conduct of one's practice; attention focused
      on one's own performance and the performance of others to the task at hand;
      rehearsal and proper preparation and contingency planning for procedures;
      effective communication so that information is accurate, adequate, unambiguous,
      and confirmed; and sense-making, or an understanding and verification of
      consistency between what is observed and expected and between what is planned and
      the premises for those plans.

PMID- 16105518
TI  - The influence of practice schedules in the learning of a complex bone-plating
      surgical task.
AB  - BACKGROUND: Practicing surgical tasks on bench models can be arranged in 3 ways:
      as the entire task, or as individual skills practiced separately in blocked or
      random order. The issue of the optimal practice schedule for the acquisition of
      surgical tasks is critical for enhancing training programs. METHOD: An orthopedic
      bone-plating task was practiced as a whole, or in parts in either a random or a
      blocked order. Learning was assessed on global ratings, checklists, and final
      product analysis before, immediately after, and an hour after practice. RESULTS:
      Checklists, and final product analysis, but not the global ratings showed that
      practicing the entire task resulted in the most learning, followed by the random
      practice. Practice of the skills in a blocked order yielded the least amount of
      learning. CONCLUSIONS: It is recommended that surgical tasks composed of several
      discrete skills should be practiced as a whole. However, if part practice is
      necessary, these skills should be arranged in random order to optimize learning.

PMID- 16105519
TI  - Portal vein tumor thrombus in colorectal liver metastasis.

PMID- 16105520
TI  - Is breast cancer sentinel lymph node mapping valuable for patients in their
      seventies and beyond?
AB  - BACKGROUND: Axillary lymph node dissection (ALND) is performed less commonly for
      the axillary staging of elderly patients because it is felt to uncommonly alter
      therapy. Sentinel lymph node (SLN) dissection can accomplish axillary staging
      with less morbidity, but it is unclear if it alters subsequent therapy. METHODS:
      Review of a prospectively collected breast cancer SLN mapping database. Medical
      records were reviewed to supplement the database. RESULTS: Among 730 breast
      cancer SLN mapping patients, 261 (35.8%) were >or=70 years of age (range 70 to
      95). The overall SLN identification rate was 98.8% among those <70 and 97.1% for
      those >or=70 (P=.11) and 100% and 99.4%, respectively (P=.25), among the most
      recent 500 patients. SLN metastases were detected by hematoxalin and eosin
      staining (H&E) in 24.2% of those <70 and 13.4% of those >/=70 (P<.01) and by
      immunohistochemistry staining (IHC) only in 4.6% and 5.0% of patients,
      respectively. No elderly patients with histologically negative SLNs underwent
      ALND, but 88.9% of patients with H&E metastases and 84.6% with IHC metastases
      underwent ALND. Of the H&E-positive women, 88% underwent adjuvant systemic
      therapy versus 55% of H&E-negative women (P<.01). Hormonal therapy was
      administered to 86.9% of SLN-positive women and 54.3% of SLN-negative women
      (P<.01) and cytotoxic chemotherapy was administered to 24% of SLN-positive
      patients versus 2.8% of SLN-negative patients (P<.01). SLN status was associated
      with significantly different rates of systemic therapy for patients with tumors
      <1 cm and 1 to 2 cm, but not with tumors >2 cm. Mean follow-up was 15.4 months.
      No patient experienced local or regional recurrence. Distant metastases occurred
      in 8.2% of patients with SLN metastases and in no patients with negative SLNs
      (P<.01). CONCLUSIONS: The results of SLN mapping and biopsy in elderly patients
      significantly influences subsequent therapy decisions, including ALND, hormonal
      therapy, and cytotoxic chemotherapy. SLN biopsy should be recommended to elderly
      breast cancer patients.

PMID- 16105521
TI  - Lymphatic mapping and sentinel lymphadenectomy prior to neoadjuvant chemotherapy
      in patients with large breast cancers.
AB  - BACKGROUND: Lymphatic mapping and sentinel lymphadenectomy (LM/SL) accurately
      evaluates the axilla in patients with small breast cancers. LM/SL in patients
      with large breast cancers is controversial. We examined the accuracy of LM/SL
      prior to neoadjuvant chemotherapy in patients with large (>3.5 cm) breast
      cancers. METHODS: Patients with large breast cancers underwent LM/SL prior to
      neoadjuvant chemotherapy using 99m-technetium radiocolloid and isosulfan-blue dye
      technique. RESULTS: Twenty-one patients with large (median 5.0 cm) breast cancers
      underwent LM/SL prior to neoadjuvant chemotherapy. Twelve patients had a tumor
      free sentinel node (SN) and received doxorubicin-based chemotherapy; 9 patients
      had disease in the SN and received doxorubicin followed by a taxane. No patient
      progressed while receiving neoadjuvant chemotherapy, nor has there been an
      axillary recurrence (median 36 months). CONCLUSIONS: LM/SL performed prior to
      neoadjuvant chemotherapy in patients with large breast cancers is an accurate
      method of axillary staging. Axillary staging prior to neoadjuvant chemotherapy
      may have prognostic and therapeutic implications.

PMID- 16105522
TI  - Presentation, treatment, and multivariate analysis of risk factors for
      obstructive and perforative colorectal carcinoma.
AB  - BACKGROUND: It is known that emergency surgery for colorectal cancer is
      associated with high morbidity and mortality. The aim of this study was to assess
      the presentation, treatment, and outcome of patients with complicated colorectal
      cancer. Risk factors for morbidity and mortality were also evaluated. METHODS:
      From 1991 to 2002, the medical records of 107 consecutive patients undergoing
      emergency surgery for obstructing or perforating colorectal carcinoma were
      retrospectively reviewed. Information regarding patient and tumor
      characteristics, treatment, and outcome was recorded. Risk factors were assessed
      by multivariate analysis. RESULTS: Eighty-three patients (78%) had complete
      obstruction and 24 (22%) had perforation. Overall and major complications
      occurred in 70% and 34%, respectively. The mortality rate was 15%. Independent
      risk factors for major morbidity were perioperative blood transfusion and high
      American Society of Anesthesiologists (ASA) class, whereas those for mortality
      were older age and high Acute Physiology and Chronic Health Evaluation II (APACHE
      II) score. CONCLUSIONS: Emergency surgery for complicated colorectal carcinoma
      carries high rates of morbidity and mortality. To achieve improvements in
      outcome, intensive treatment after surgery in patients with risk factors is
      recommended.

PMID- 16105523
TI  - Is transarterial chemoembolization necessary before liver transplantation for
      hepatocellular carcinoma?
AB  - BACKGROUND: Transarterial chemoembolization (TACE) before liver transplantation
      (LT) for hepatocellular carcinoma (HCC) has been proposed to prevent tumor
      progression, thus decreasing tumor recurrence and increasing survival. METHODS:
      We studied 46 patients undergoing LT for HCC who were divided in 2 groups--group
      A with pretransplant TACE (18 patients [39.1%]) and group B without pretransplant
      TACE (28 patients [60.9%])--and compared postoperative and long-term results
      between the 2 groups. RESULTS: There were no statistical differences in
      morbidity, transfusion needles, and postoperative time between-and no acute
      arterial or portal complication in-the 2 groups. There were no statistical
      differences in tumor recurrence (16.7 % vs 36.4 %, P=.16) with regard to pathway
      (mainly extrahepatic) or time. In group A patients, mean survival was 89.3+/-21.7
      months with 1-, 3-, and 5-year actuarial survival rates of 83.3%, 60.5%, and
      60.5%, respectively. In group B patients, mean survival was 75.1+/-19.1 months
      with 1-, 3-, and 5-year actuarial survival rates of 77.2%, 58.7%, and 38.1%,
      respectively. The differences in mean survival were not statistically significant
      (PX .56), nor was 5-year disease-free survival, which was 54% in group A and
      39.5% in group B (P=.8). CONCLUSIONS: TACE is a safe procedure for candidates on
      the wait list who are scheduled for LT to treat HCC. Although TACE does not
      correlate with increased intraoperative difficulties or postoperative
      complications, it does not significantly improve tumor recurrence and survival.

PMID- 16105524
TI  - Does technique alter quality of life after pilonidal sinus surgery?
AB  - BACKGROUND: Pilonidal sinus is a common disease in young adults that carries high
      postoperative morbidity and patient discomfort. Controversy still exists about
      the best surgical technique for the treatment of the disease in terms of
      recurrence rate and patient discomfort. METHODS: From January 2000 to November
      2003, 100 consecutive age- and sex-matched patients with chronic pilonidal sinus
      disease were randomized to receive surgical treatment in the forms of either
      excision and primary closure or rhomboid excision and Limberg flap. Time to
      return to work and to complete healing were recorded. To evaluate quality of life
      and patient comfort, all patients were asked to complete a questionnaire
      including short form 36, Visual Analogue Scale, time to sitting on toilet without
      pain, and time to walking without pain 3 months after surgery. RESULTS: Each
      group was composed of 50 patients. Mean follow-up was 19 months. There was a
      significant difference between the groups in terms of length of hospital stay
      (P=.005), time to complete healing (P<.001), time off work (P<.001), and wound
      infection rate (P=.03). Statistically significant differences were noted between
      the groups in items of general health perception (71.1+/-11.7 vs 78.2+/-14.1;
      P=.008), social functioning (87.3+/-32.8 vs 110.4+/-33.8; P=.001), and pain
      (54.5+/-14.0 vs 67.5+/-18.4; P<.001). Times to sitting on toilet and walking
      without pain showed significant differences between the groups (P=.006 and
      P<.001, respectively). The mean postoperative Visual Analogue Scale scores were
      6.5+or= 1.7 and 7.4+/- 1.4, respectively (P<.001). CONCLUSIONS: Shorter hospital
      stay, earlier healing, shorter time off work, lower ratio of complications, lower
      pain perception, and improved general health perception are the main advantages
      of te Limberg flap technique in pilonidal sinus surgery. All together, these
      parameters add to patient comfort and satisfaction after surgical treatment.

PMID- 16105525
TI  - Intraoperative splanchnic hypoperfusion, increased intestinal permeability, down
      regulation of monocyte class II major histocompatibility complex expression,
      exaggerated acute phase response, and sepsis.
AB  - BACKGROUND: A compromised gut barrier function may be associated with systemic
      inflammatory response syndrome, sepsis, and multiple organ dysfunction syndrome
      in patients after major trauma or critical illness, and inadequate oxygenation of
      the gut mucosa has been incriminated as an underlying mechanism. The focus of
      this study was the relationship of splanchnic hypoperfusion to regional and
      systemic immune responses after major surgery. METHODS: Patients (n=20)
      undergoing curative oncologic resection of the esophagus or esophagogastric
      junction were studied. Gastric mucosal pH level was monitored by gastric
      tonometry. The expression of class II major histocompatibility complex antigen
      (human leukocyte antigen-DR) and L-selectin on systemic monocytes was assessed
      before surgery, during surgery (as well as portal monocytes), and for 1 week
      after surgery, along with C-reactive protein levels. Intestinal permeability was
      measured before surgery and on the first and seventh postoperative days by using
      dual sugar probes. RESULTS: Significant mucosal acidosis (pH<7.1)
      intraoperatively was evident in 5 patients (25%), and a further 7 patients (35%)
      had a nadir gastrointestinal mucosal pH level between 7.1 and 7.2. Severe (<7.1)
      mucosal acidosis was associated significantly (P< .05) with postoperative septic
      complications, an increase in postoperative intestinal permeability, C-reactive
      protein and L-selectin expression, and a decrease (P< .05) in monocyte human
      leukocyte antigen-DR expression. CONCLUSIONS: Intraoperative splanchnic
      hypoperfusion is associated significantly with down-regulation of monocyte
      function, increased intestinal permeability, and an exaggerated acute phase
      response. This suggests that splanchnic hypoperfusion alters local and systemic
      immune function, supporting the thesis that the gut has a central role in the
      immunoinflammatory response to major surgery.

PMID- 16105526
TI  - Risk factors and outcomes of pancreatitis after open heart surgery.
AB  - BACKGROUND: We sought to analyze the risk factors and natural history associated
      with post-cardiac surgery acute pancreatitis. METHODS: Retrospective analysis of
      all patients having undergone cardiac surgery at our hospital between January 1,
      1992, and October 1, 2001. RESULTS: A total of 10,249 cardiac operations were
      performed. Thirty-nine (0.4%) patients developed postoperative pancreatitis.
      There was a higher incidence during the period spanning 1992 through 1996 than
      1997 through 2001 (0.6% versus 0.2%, P< .05). Patients with pancreatitis had
      longer postoperative length of stay (51+/-5 days versus 10+/-1 days, P<.05) and a
      greater in-hospital mortality rate (28% versus 4%, P<.05) than patients who did
      not develop pancreatitis. A history of alcohol abuse, cardiac surgery performed
      during 1992 to 1996, increased cardiopulmonary bypass time, and increased cross
      clamp time were independent risk factors for the development of pancreatitis.
      Multiple-organ failure was an independent predictor for death among patients with
      pancreatitis. CONCLUSIONS: Although the frequency of post-cardiac surgery
      pancreatitis is diminishing, it is still associated with significant mortality.

PMID- 16105527
TI  - An analysis of cost and clinical outcome in palliation for advanced pancreatic
      cancer.
AB  - BACKGROUND: The optimal palliative method for patients with unresectable
      pancreatic cancer remains controversial. METHODS: A retrospective chart review
      evaluated patients who underwent exploration for presumed resectable pancreatic
      cancer. Cost-based analysis was performed using relative value units (RVUs) that
      included the initial surgical procedure and any additional procedure required to
      achieve satisfactory palliation. RESULTS: Of 96 patients (1993--2002), 6% had
      biliary bypass, 42% had duodenal bypass, 40% had double bypass, and 13% had no
      procedure with equivalent clinical outcomes. If biliary bypass was not initially
      performed, there was a significant incidence of biliary complications before
      definitive endoscopic stenting (P=.01). If duodenal bypass was not initially
      performed, 11% developed duodenal obstruction (P=.04). Total RVUs was highest for
      a double bypass and lowest for no initial surgical palliative procedure.
      CONCLUSIONS: Although surgical bypass procedures at initial exploration provide
      durable palliation, these procedures are associated with greater costs.

PMID- 16105528
TI  - Oral trypsin inhibitor can improve reflux esophagitis after distal gastrectomy
      concomitant with decreased trypsin activity.
AB  - BACKGROUND: The pathogenesis of reflux esophagitis is not well understood and
      remains controversial. Distal gastrectomy serves as a model to assess the role of
      duodenal reflux with low gastric acidity in the development of reflux
      esophagitis. We investigated the clinical usefulness and antitrypsin activity
      after treatment with a trypsin inhibitor, camostat mesilate, against the reflux
      esophagitis after distal gastrectomy reconstructed with Billroth-I anastomosis.
      METHODS: Twenty-eight patients with gastroesophageal reflux disease after distal
      gastrectomy were prescreened according to esophageal pH level and trypsin
      activity, and consequently 11 patients were enrolled in the present clinical
      study. Esophageal and duodenal washings were aspirated for the evaluation of the
      pretreatment trypsin activity. Then 100 mg of camostat mesilate was administered
      orally. At 30 and 120 minutes after the administration, duodenal washings were
      aspirated for the evaluation of posttreatment trypsin activity. Thereafter, 300
      mg of camostat mesilate was administered orally 3 times daily for a 4-week
      period. On the 28th day of administration, the grade of reflux esophagitis (Los
      Angeles classification) was re-evaluated under endoscopy and the esophageal
      washings were aspirated for the evaluation of trypsin activity. RESULTS: The
      trypsin activities in the duodenum both at 30 and 120 minutes after oral
      ingestion of camostat mesilate were decreased significantly in comparison with
      those in the pretreatment period in each patient (P<.001). In 6 of 7 patients
      with detectable trypsin activity in the esophagus, the activities after the 28th
      day of treatment were lower than those in the pretreatment period, and the
      symptoms were milder than those before treatment (P<.05). Furthermore, endoscopic
      evaluation showed that 40% of patients were grade B, C, and D after treatment
      (28th day), whereas 70% of patients were grade B, C, and D before the treatment.
      CONCLUSIONS: Oral administration of trypsin inhibitor can improve reflux
      esophagitis after distal gastrectomy concomitant with decreased trypsin activity.

PMID- 16105529
TI  - Total thyroidectomy for multinodular goiter in the elderly.
AB  - BACKGROUND: Total thyroidectomy for multinodular goiter (MNG) is increasingly
      being performed for the elderly population and yet their perioperative and long
      term outcomes remain unclear. METHODS: A total of 279 patients who underwent
      total thyroidectomy for MNG in a university-based hospital during a 9-year period
      were analyzed according to their age at the time of operation. RESULTS: The
      duration of operation (P=.023), intraoperative blood loss (P=.030), weight of
      resected thyroid glands (P<.001) and proportion of retrosternal goiter (P<.001)
      were significantly greater in the elderly group (>/=70 years) (n = 55), but the
      incidence of surgically related complications, including recurrent laryngeal
      nerve palsy and hypoparathyroidism, was similar. Postoperative pneumonia occurred
      more frequently in the elderly group (P=.034). The number of comorbidities tended
      to correlate with the length of hospital stay and long-term survival in elderly
      patients. CONCLUSIONS: Total thyroidectomy for MNG in elderly patients had a
      similar perioperative outcome as their younger counterparts, but their long-term
      outcome is likely to be influenced by the number of comorbidities.

PMID- 16105530
TI  - Randomized study on oral administration of calcitriol to prevent symptomatic
      hypocalcemia after total thyroidectomy.
AB  - BACKGROUND: Symptomatic hypocalcemia remains the main postoperative complication
      after total thyroidectomy. The aim of the present study was to evaluate the role
      of oral supplementation of calcitriol and calcium salts in preventing severe
      postoperative hypocalcemia after total thyroidectomy. METHODS: A consecutive
      series of patients undergoing total thyroidectomy followed by administration of
      500 mg of calcium salts 3 times per day were randomized to 3 different
      postoperative medical treatments: in group A, .5 microg of calcitriol twice per
      day was administered to 104 patients; in group B, 1 mmicrog of calcitriol twice
      per day was administered to 111 patients; and in group C, 202 patients did not
      receive calcitriol. RESULTS: The rate of postoperative tetany in group A was
      2.9%, in group B was 0%, and in group C was 7.4% (P=.03) and the rate of
      paresthesias was 28.8%, 17.1%, and 22.3%, respectively (P=.19). At
      discontinuation of calcitriol/calcium salts treatment, intact parathyroid hormone
      levels did not significantly differ from the preoperative levels. Receiver
      operating characteristic (ROC) curve analysis showed that the area under the
      curve for serum concentration of calcium in predicting postoperative tetany was
      .749, .858 and .862 on the first, second, and third postoperative day,
      respectively. The best cut-off value of calcemia for prediction tetany was 7.5
      mg/dL, and the rate of severe hypocalcemia on the third postoperative day was
      23.1% in group A, 9.9% in group B, and 27.2% in group C (P=.001). CONCLUSIONS:
      Oral administration of 1 microg of calcitriol twice per day and 500 mg of calcium
      salts 3 times per day after total thyroidectomy significantly decreases the risk
      of severe postoperative hypocalcemia.

PMID- 16105531
TI  - Biliary peritonitis requiring reoperation after removal of T-tubes from the
      common bile duct.
AB  - BACKGROUND: Bile peritonitis can occur when a T-tube is electively removed from
      the common bile duct, but this is regarded as a rare complication. Plastic T
      tubes are known to increase this risk and should not be used. Latex rubber T
      tubes are preferred, but the peritonitis can still occur. METHODS: Prospective
      data were collected on 1375 patients who underwent common bile duct exploration
      between March 20, 1994 and March 20, 2003. RESULTS: Thirty-four (2.47%) patients
      experienced generalized bile peritonitis after T-tube removal from the common
      bile duct. Mean age was 63.65 years. In all cases, a soft silicon-coated latex
      rubber T-tube was placed into the bile duct. All T-tubes were removed 21 days
      after surgery. Thirty-four patients developed acute generalized biliary
      peritonitis immediately after T-tube removal and required urgent active
      intervention. The mortality rate was 5.9%, and the mean hospital stay was 14.6
      days. CONCLUSIONS: The most common causes of lack of formation of T-tube tract
      and operative procedure were unknown and T-tube reinsertion, respectively. T-tube
      removal can result in significant morbidity and mortality.

PMID- 16105532
TI  - Colonic anastomosis performed with a memory-shaped device.
AB  - BACKGROUND: The present study was prompted by our previous successful experience
      with the compression anastomosis clip (CAC) on animals followed by a study on 20
      patients scheduled for colonic resection. METHODS: Sixty patients with colonic
      cancer were assigned randomly to undergo an anastomosis either with the CAC or a
      stapler. To perform anastomosis with CAC, the 2 edges of the resected colon are
      aligned. Two 5-mm incisions are made close to the edges, through which (using a
      special applier) the CAC, after being cooled in ice water, is introduced in an
      open position. In response to the body temperature, the clip resumes its original
      (closed) position, thereby clamping the 2 bowel segments together. At the same
      time, a small scalpel incorporated in the applier makes a small incision through
      the clamped walls for the passage of gas and feces. The clip is detached from the
      applier to be left inside the intestine. The 2 5-mm incisions are sutured. The
      clip is expelled with the stool within 5 to 7 days, creating a perfect uniform
      compression anastomosis. RESULTS: Neither group had anastomotic complications
      such as leakage or obstruction. All the other parameters were better in the study
      group than in the control patients. CONCLUSIONS: The use of the CAC for colonic
      surgery is safe, simple, efficient, shortens operation time, and is almost what
      we call the "no-touch concept" in surgery and may decrease infection.

PMID- 16105533
TI  - Sex differences in cytokine production and surface antigen expression of
      peripheral blood mononuclear cells after surgery.
AB  - BACKGROUND: Several clinical and epidemiological studies have observed a better
      outcome after sepsis in women than in men. The purpose of this study was to
      determine if these sex differences are observed in cytokine responses and the
      surface antigen expression of monocytes. In addition, the clinical courses of
      male and female patients after gastrointestinal surgery were compared. METHODS: A
      total of 25 patients with gastric carcinoma who underwent gastrectomy were
      enrolled in this study. Tumor necrosis factor-alpha (TNF-alpha), interleukin-10,
      and interferon-gamma (IFN-gamma) production by lipopolysaccharide-stimulated
      peripheral blood mononuclear cells (PBMCs) as well as the expression of Toll-like
      receptor-4 (TLR-4), TLR-2, human leukocyte antigen-D related (HLA-DR), and CD16
      on monocytes in 16 men and 9 women on the day before surgery were compared with
      measurements on postoperative day (POD) 1. Furthermore, postoperative infectious
      complications, the development of systemic inflammatory response syndrome, and
      serum C-reactive protein levels on POD3 were compared. RESULTS: TNF-alpha
      production of PBMCs and TLR-2 and CD16 expression on monocytes were significantly
      higher in women than in men before surgery. IFN-gamma production of PBMCs and HLA
      DR expression on monocytes were significantly lower in men than in women on POD1.
      Furthermore, TNF-alpha production of PBMCs on POD1 was significantly increased,
      and both IFN-gamma production and HLA-DR expression were significantly decreased
      compared with that observed before surgery in men, but no corresponding
      significant changes were observed in women. In addition, C-reactive protein
      levels on POD3 were significantly higher in men than in women. CONCLUSIONS: Both
      TNF-alpha and interleukin-10 production of PBMCs and both TLR-2 and CD16
      expression on monocytes were significantly higher in women than in men on the day
      before surgery. Excessive TNF-alpha and suppressive IFN-gamma production of
      PBMCs, as well as a decrease in HLA-DR expression on monocytes, occurred more
      often in men than in women after surgery, suggesting that these factors all
      contribute to an increased susceptibility of men to develop systemic inflammatory
      response syndrome or postoperative infectious complications.

PMID- 16105534
TI  - Acid normalization and improved esophageal motility after Nissen fundoplication:
      equivalent outcomes in patients with normal and ineffective esophageal motility.
AB  - BACKGROUND: Severe gastroesophageal reflux disease may result in acquired
      esophageal dysmotility. The correct surgical approach to associated
      gastroesophageal reflux disease and dysmotility is controversial, in particular
      whether the "gold-standard" total fundoplication of Nissen is appropriate
      compared with partial fundoplication. Our unit has performed total fundoplication
      for all patients, irrespective of esophageal motility, and this article describes
      that experience. METHODS: Ninety-eight patients undergoing antireflux surgery
      were divided into 2 groups. Group 1 (n=60) consisted of patients with normal
      esophageal motility, and group 2 (n=38) had dysmotility. All patients underwent
      preoperative and postoperative manometry, 24-hour pH testing, symptom scoring,
      and quality-of-life assessment. RESULTS: The median postoperative acid score was
      not significantly different between groups 1 and 2. Eighty-eight percent of
      patients with normal motility and 89% of patients with dysmotility had no
      symptoms or minor symptoms, with a significant improvement in quality of life 6
      months after surgery. There was a significant increase in esophageal wave
      amplitude in both groups, and 20 patients (53%) in the dysmotility group reverted
      to normal motility after surgery. Recurrent symptoms were associated with
      postoperative abnormal pH profiles in 5 patients from group 1 and 3 from group 2.
      CONCLUSIONS: Preoperative dysmotility is not a contraindication for total
      fundoplication. Postoperative acid control is associated with improved esophageal
      clearance and symptoms.

PMID- 16105535
TI  - Surgical outcome of patients with hepatocellular carcinoma originating in the
      caudate lobe.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) originating in the caudate lobe is
      rare, and the treatment for this type of carcinoma is difficult because of its
      unique anatomic location. METHODS: This retrospective study assessed the surgical
      outcome of patients with caudate lobe HCC. There were 20 cases of HCC originating
      in the caudate lobe among 435 patients with primary HCC who underwent hepatic
      resection in our department from 1990 to 2002. The caudate tumors were located in
      the Spiegel lobe in 3 patients, the paracaval portion in 15 patients, and the
      caudate process in 2 patients. Surgical procedures consisted of limited resection
      of the caudate lobe in 6 patients and extended caudate lobectomy in 14 patients.
      Recurrence was recognized in 12 patients, including 8 patients with multiple
      intrahepatic recurrences, 1 with peritoneal dissemination, and 1 with lymph node
      metastasis. RESULTS: There was no significant difference in postoperative
      survival rate between patients who underwent limited resection of the caudate
      lobe and those who underwent extended caudate lobectomy. Compared with 415
      patients with HCC originating in other locations, the 20 patients with caudate
      lobe HCC showed significantly more intraoperative blood loss (P<.05), longer
      operation time (P<.0001), and more postoperative complications (P<.005).
      Intrahepatic recurrence was more frequent in the caudate lobe HCC compared with
      HCC originating in other locations (40% vs 17.6%; P<.05). There was a
      significantly poor survival rate in the postoperative patients with caudate HCC
      (25.9% vs 54.1% for five-year survival; P=.01). Intrahepatic multiple recurrences
      were frequently recognized in the patients with caudate lobe HCC, indicating no
      significance for extended caudate lobectomy. CONCLUSIONS: Because of the
      relatively poor prognosis in patients with caudate lobe HCC, adjuvant therapy
      combined with surgical operation should be considered.

PMID- 16105536
TI  - Microcirculatory hemodynamics after acute blood loss followed by fresh and banked
      blood transfusion.
AB  - BACKGROUND: Red blood cell (RBC) conformational changes occur when blood is
      stored. This study was designed to be a preliminary evaluation to assess how
      these changes affect the microcirculation. METHODS: The rat cremaster muscle flap
      model was used to evaluate in vivo microcirculatory changes after withdrawal of 1
      mL blood with subsequent administration of fresh blood (group I, n=6) and banked
      blood (group II, n=6). Each group underwent a 3-stage evaluation: baseline, after
      blood withdrawal, and after transfusion. Using intravital microscopy, RBC
      velocity, vessel diameter, functional capillary perfusion, and leukocyte
      endothelial interactions were noted. RESULTS: After blood withdrawal, changes in
      RBC velocity, vessel diameter, functional capillary perfusion, and number of
      activated leukocytes were observed in both groups, but these changes were more
      significant in stored blood compared with fresh blood (P<or=.05). CONCLUSIONS:
      Further work is needed to validate these findings, but these preliminary data
      suggest that stored blood may have a deleterious effect on the microcirculation.

PMID- 16105537
TI  - The effect of aprotinin in a model of uncontrolled hemorrhagic shock.
AB  - BACKGROUND: Aprotinin has been shown to promote clot formation through its
      antifibrinolytic activity, by inhibiting the plasmin-induced complement
      activation and by protecting the platelets adhesive surface receptors. It has
      been successfully used in cardiac and liver transplantation surgery. OBJECTIVE:
      To evaluate the effect of aprotinin in a model of uncontrolled intra-abdominal
      bleeding as a basis for its potential use in trauma patients. METHODS: Twenty
      rats were randomly divided into 2 groups. All animals were operated on and
      bleeding was induced by transecting 1 lobe of the liver. In the treatment group a
      single dose of 30,000 U/kg of aprotinin was administered 5 minutes after the
      injury. The animals were monitored for hemodynamic parameters, blood loss volume,
      and mortality rates. RESULTS: At 120 minutes from trauma induction a significant
      difference in mean blood pressure was observed: 67+/-22 mm Hg in the treatment
      group versus 53+/-28 mm Hg in the control group (P=.04). This difference remained
      consistent until the end of the experiment. Treatment with aprotinin also
      resulted in a tendency to an increased survival rate (P=.05) and increased mean
      survival time: 175+/-46 minutes as compared to 123+/-48 minutes in the controls
      (P=.027). CONCLUSIONS: Early administration of aprotinin resulted in temporary
      hemodynamic stabilization and prolonged survival in a model of uncontrolled
      bleeding. Further studies are needed to establish the possible use of aprotinin
      in the treatment of trauma patients.

PMID- 16105538
TI  - Pregnancy outcome following non-obstetric surgical intervention.
AB  - OBJECTIVE: To evaluate the effects of non-obstetric surgical procedures on
      maternal and fetal outcome. METHODS: A systematic review of all English language
      literature. RESULTS: Fifty-four papers met the inclusion criteria. The overall
      number of patients reported was 12,452. Reported maternal death was rare at
      .006%. The miscarriage rate was 5.8%; however, this number is difficult to
      interpret since matched controls were not available. The rate of elective
      termination of pregnancy following non-obstetric surgery was 1.3%. The rate of
      premature labor induced by non-obstetric surgical intervention was 3.5% and this
      was noted specifically following appendectomy versus other types of interventions
      (P<.001). A total of 2.5% of pregnancies resulted in fetal loss. The prematurity
      rate was 8.2%. The rate of major birth defects among women who underwent non
      obstetric surgical intervention in the first trimester was 3.9%. Sub-analysis of
      papers reporting on appendectomy during pregnancy revealed a high rate (4.6%) of
      surgery-induced labor. Fetal loss associated with appendectomy was 2.6%; however,
      this rate was increased when peritonitis was present (10.9%). CONCLUSIONS: Modern
      surgical and anesthesia techniques appear to diminish the rate of maternal death.
      Surgery in the first trimester does not appear to increase major birth defects
      and should not be delayed when indicated. Acute appendicitis with peritonitis is
      associated with higher risk to the mother and fetus.

PMID- 16105539
TI  - A systematic review of whether oral contrast is necessary for the computed
      tomography diagnosis of appendicitis in adults.
AB  - BACKGROUND: There are several methods of contrast administration when performing
      computed tomography (CT) scanning for suspected appendicitis. In this systematic
      review we evaluated the diagnostic performance of CT with and without contrast
      material. METHODS: Twenty-three reports were identified using a Medline search.
      RESULTS: The aggregated diagnostic performance characteristics of all modes of CT
      scanning were excellent with a range of sensitivity (83--97%), specificity (93-
      98%), positive predictive value (86--98%), negative predictive value (94--99%),
      and accuracy (92--97%). The diagnostic performance of CT without oral contrast
      was similar (sensitivity, 95% vs. 92% [not statistically significant]; negative
      predictive value, 96% for both protocols) or surprisingly better (specificity,
      97% vs. 94%; positive predictive value, 97% vs. 89%; accuracy, 96% vs. 92%;
      P<.0001) than with oral contrast. CONCLUSIONS: Noncontrast CT techniques to
      diagnose appendicitis showed equivalent or better diagnostic performance compared
      with CT scanning with oral contrast. A prospective comparative trial of CT with
      and without oral contrast for appendicitis should be performed to assess the
      adequacy of this modality.

PMID- 16105540
TI  - Are we giving enough coagulation factors during major trauma resuscitation?
AB  - Hemorrhage is a major cause of trauma deaths. Coagulopathy exacerbates hemorrhage
      and is commonly seen during major trauma resuscitation, suggesting that current
      practice of coagulation factor transfusion is inadequate. Reversal of
      coagulopathy involves normalization of body temperature, elimination of the
      causes of disseminated intravascular coagulation (DIC), and transfusion with
      fresh-frozen plasma (FFP), platelets, and cryoprecipitate. Transfusion should be
      guided by clinical factors and laboratory results. However, in major trauma,
      clinical signs may be obscured and various factors conspire to make it difficult
      to provide the best transfusion therapy. Existing empiric transfusion strategies
      for, and prevailing teachings on, FFP transfusion appear to be based on old
      studies involving elective patients transfused with whole blood and may not be
      applicable to trauma patients in the era of transfusion with packed red blood
      cells (PRBCs). Perpetuation of such concepts is in part responsible for the
      common finding of refractory coagulopathy in major trauma patients today. In this
      review, we argue that coagulopathy can best be avoided or reversed when severe
      trauma victims are transfused with at least the equivalent of whole blood in a
      timely fashion.

PMID- 16105541
TI  - Clinical kidney transplantation: a 50th anniversary review of the first reported
      series.
AB  - BACKGROUND: Histories of kidney transplantation rarely mention a series reported
      by Gordon Murray of Toronto and published by the American Journal of Surgery 50
      years ago. METHODS: The papers and biographies of Gordon Murray were reviewed in
      the context of knowledge at that time about renal failure management to determine
      their contribution to transplantation research and to current practice. RESULTS:
      Murray proceeded from a unique leadership position in vascular surgery,
      anticoagulation therapy, and dialysis to undertake a rational series of animal
      experiments and human trials of kidney transplantation that led him to the
      practices of graft irrigation, cold storage, pelvic graft placement, renal-to
      iliac vascular anastomoses, and ureterovesical anastomosis that continue to be
      used today. His animal studies included the first attempts to use
      immunosuppression and total body irradiation to prevent rejection. His
      observation that rejection may result in graft thrombosis and his attempts to
      prevent it with heparin anticipated current efforts to use newer agents for the
      same purpose in sensitized allotransplantation and xenotransplantation.
      CONCLUSIONS: Modern renal transplantation is founded on many of the principles
      expounded by Gordon Murray 50 years ago.

PMID- 16105542
TI  - Systematic appraisal of the management of the major vascular complications of
      pancreatitis.
AB  - BACKGROUND: This study is a systematic appraisal of the management of major
      vascular complications of pancreatitis conducted by collating individual patient
      episode data from published literature. METHODS: Searches identified 79 papers of
      which 62 provided detailed information on the clinical course of 214 patients.
      Principal outcomes were modes of presentation, results of diagnostic angiography,
      and embolization and overall outcome. RESULTS: There were 160 "spontaneous" and
      40 postoperative episodes of hemorrhage. Underlying pancreatic disease was
      chronic pancreatitis (40), pseudocyst (135), and acute pancreatitis in 39.
      Angiography was undertaken in 173 (81%) with embolization attempted in 115 and
      achieving hemostasis in 85 (75%). There were 40 (19%) deaths. Mortality was
      greater in patients undergoing surgery as first intervention compared with
      angiography first (P = .01, Fisher exact test). CONCLUSION: This analysis of
      pooled data provides evidence of a central role for mesenteric angiography in the
      diagnosis of major vascular complications of pancreatitis and for angiographic
      embolization as a powerful tool for achieving hemostasis.

PMID- 16105543
TI  - Laparoscopic lymph node dissection after endoscopic submucosal dissection: a
      novel and minimally invasive approach to treating early-stage gastric cancer.
AB  - BACKGROUND AND OBJECTIVE: Endoscopic submucosal dissection (ESD), a newly
      developed endoscopic mucosal resection (EMR) technique, can completely cure a
      differentiated mucosal gastric cancer smaller than 2 cm. For early-stage gastric
      cancers (EGCs) deviating from the above-mentioned criterion, gastrectomy with
      lymph node dissection is performed for potential risk of lymph node metastasis
      (LNM). However, many of surgical EGC cases actually do not have LNM, indicating
      this surgery may not be necessary for many cases of EGC. To avoid this
      unnecessary surgery, we have introduced laparoscopic lymph node dissection (LLND)
      after ESD. Standard gastrectomy with extended lymph node dissection is indicated
      for patients if LLND reveals LNM. We present our novel approach and the
      preliminary results of EGC patients having potential risk of LNM. METHODS: Five
      patients with EGC deviating from the EMR criterion underwent the combination of
      ESD and LLND. ESD was performed using a newly developed insulation-tipped
      diathermic knife. Lymph nodes, which were determined on the basis of the location
      of the primary tumor and lymphatic drainage of the stomach, were removed
      laparoscopically. The lymphatic drainage was visualized by submucosally injecting
      indocyanine green (ICG) around the post-ESD ulcerative scars during
      intraoperative gastroscopy. RESULTS: The ESD enabled en bloc resection without
      any complications. The resected margins of all the lesions were free of cancer
      cells vertically and horizontally. LLND was successfully performed without any
      complications. The mean number of the dissected lymph nodes was 15 (range 6 to
      22). In 4 of the 5 patients, the dissected lymph nodes were free of cancer cells,
      and therefore, the combination of ESD and LLND was considered a definitive
      treatment. The remaining patient was found to have LNM but chose not to undergo
      any surgery. During follow-ups, the patients' previous quality of life was
      restored without any tumor recurrence. CONCLUSIONS: The combination of ESD and
      LLND enables the complete resection of the primary tumor and the histologic
      determination of lymph node status. This combination treatment is a potential,
      minimally invasive method, and may obviate unnecessary gastrectomy without
      compromising curability for EGC patients having the potential risk of LNM.

PMID- 16105544
TI  - Use of a new sealing device to simplify jejunal resection during
      pancreaticoduodenectomy.
AB  - BACKGROUND: Pancreaticoduodenectomy has undergone numerous technical
      modifications since the original reported series in 1935, but little focus has
      been directed to the dissection and ligation of the mesenteric blood supply to
      the first portion of the jejunum. METHODS: Sixty-four patients in whom the device
      was used were compared to a historical cohort of 128 patients who had undergone
      pancreaticoduodenectomy at our institution. RESULTS: The technique described
      provided a rapid, ergonomically efficient method to complete step 5 of
      pancreaticoduodenectomy. We found no differences in average hospital length of
      stay (LOS), reoperation rate, morbidity, mortality, or postoperative readmission
      rates between patients operated on before or after adoption of this technique
      CONCLUSION: The Ligasure sealing device (Valleylab, Boulder, CO) provides an
      excellent, safe alternative to the classic use of clamps and ties when resecting
      the first portion of the jejunum during pancreaticoduodenectomy.

PMID- 16105545
TI  - Assessment of psychomotor skills acquisition during laparoscopic cholecystectomy
      courses.
AB  - BACKGROUND: Standardized short courses in laparoscopic cholecystectomy aim to
      teach laparoscopic skills to surgical trainees, although end-of-course
      assessments of performance remain subjective. The current study aims to
      objectively assess psychomotor skills acquisition of trainees attending
      laparoscopic cholecystectomy courses. METHODS: Thirty-seven junior surgical
      trainees had their laparoscopic skills assessed before and after attending 1 of 3
      separate 2-day courses (A, B, and C), all with identical format. Assessments were
      comprised of a standardized simulated laparoscopic task, with performance
      measured using a valid electromagnetic hand-motion tracking device. RESULTS:
      Overall, trainees made significant improvements in path length (P=.006), number
      of movements (P<.001), and time taken (P<.001). Analyzing the 3 courses
      separately, only trainees attending courses A and C made significant
      improvements. DISCUSSION: Objective validated methods can be used to assess
      learning of psychomotor skills on courses. In addition to providing participants
      with an insight into their skills, these data can be used to demonstrate course
      efficacy.

PMID- 16105546
TI  - Genotyping of transgenic mice: old principles and recent developments.

PMID- 16105547
TI  - HHR23A, a human homolog of Saccharomyces cerevisiae Rad23, regulates xeroderma
      pigmentosum C protein and is required for nucleotide excision repair.
AB  - HHR23A and hHR23B are the human homologs of Saccharomyces cerevisiae Rad23.
      hHR23B is associated with the nucleotide excision repair (NER) factor xeroderma
      pigmentosum C (XPC) protein and is required for global genome repair. The
      function of hHR23A is not yet clear. In this study, the potential function of the
      hHR23A protein was investigated using RNA interference techniques. The hHR23A
      knock-down (KD) construct diminished the RNA level of hHR23A protein by
      approximately 60%, and it did not interfere with expression of the hHR23B gene.
      Based on Southwestern immunoblot and host-cell reactivation assays, hHR23A(KD)
      cells were found to be deficient in DNA repair activity against the DNA damage
      caused by UVC irradiation. In these hHR23A(KD) cells, the XPC gene was not
      normally induced by UVC irradiation, indicating that the hHR23A protein is
      involved in NER through regulation of the DNA damage recognition protein XPC. Co
      immunoprecipitation experiments revealed that hHR23A was associated with a small
      portion of hHR23B and the majority of p53 protein, indicating that hHR23A
      regulates the function of XPC by its association with the NER activator p53.

PMID- 16105548
TI  - Pleiotrophin stimulates tyrosine phosphorylation of beta-adducin through
      inactivation of the transmembrane receptor protein tyrosine phosphatase
      beta/zeta.
AB  - Pleiotrophin (PTN the protein, Ptn the gene) signals through a unique mechanism;
      it inactivates the tyrosine phosphatase activity of its receptor, the
      transmembrane receptor protein tyrosine phosphatase (RPTP)beta/zeta, and
      increases tyrosine phosphorylation of the substrates of RPTPbeta/zeta through the
      continued activity of a yet to be described protein tyrosine kinase(s) in PTN
      stimulated cells. We have now found that the cytoskeletal protein beta-adducin
      interacts with the intracellular domain of RPTPbeta/zeta in a yeast two-hybrid
      system, that beta-adducin is a substrate of RPTPbeta/zeta, that beta-adducin is
      phosphorylated in tyrosine in cells not stimulated by PTN, and that tyrosine
      phosphorylation of beta-adducin is sharply increased in PTN-stimulated cells,
      suggesting that beta-adducin is a downstream target of and regulated by the
      PTN/RPTPbeta/zeta signaling pathway. beta-Catenin was the first downstream target
      of the PTN/RPTPbeta/zeta signaling pathway to be identified; these data thus also
      suggest that PTN coordinately regulates steady state levels of tyrosine
      phosphorylation of the important cytoskeletal proteins beta-adducin and beta
      catenin and, through PTN-stimulated tyrosine phosphorylation, beta-adducin may
      contribute to the disruption of cytoskeletal structure, increased plasticity, and
      loss of homophilic cell-cell adhesion that are the consequences of PTN
      stimulation of cells and a characteristic feature of different malignant cells
      with mutations that activate constitutive expression of the endogenous Ptn gene.

PMID- 16105549
TI  - Endogenous and ectopic expression of telomere regulating genes in chicken
      embryonic fibroblasts.
AB  - In this study, we compared the endogenous expression of genes encoding telomere
      regulating proteins in cultured chicken embryonic fibroblasts (CEFs) and 10-day
      old chicken embryos. CEFs maintained in vitro senesced and senescence was
      accompanied by reduced telomere length, telomerase activity, and expression of
      the chicken (c) TRF1 gene. There was no change in TRF2 gene expression although
      the major TRF2 transcript identified in 10-day-old chicken embryos encoded a
      truncated TRF2 protein (TRF2'), containing an N-terminal dimerisation domain but
      lacking a myb-related DNA binding domain and nuclear localisation signal.
      Senescence of the CEFs in vitro was associated with the loss of the TRF2'
      transcript, indicative of a novel function for the encoded protein. Senescence
      was also coupled with decreased expression of RAD51, but increased RAD52
      expression. These data support that RAD51 independent recombination mechanisms do
      not function in vitro to maintain chicken telomeres. To attempt to rescue the
      CEFs from replicative senescence, we stably transfected passage 3 CEFs with the
      human telomerase reverse transcriptase (hTERT) catalytic subunit. While hTERT
      expression was detected in the stable transfectants neither telomerase activity
      nor the stabilisation of telomere length was observed, and the transfectant cells
      senesced at the same passage number as the untransfected cells. These data
      indicate that the human TERT is incompatible with the avian telomere maintenance
      apparatus and suggest the functioning of a species specific telomere system in
      the avian.

PMID- 16105550
TI  - Gene therapy for murine glycerol kinase deficiency: importance of murine
      ortholog.
AB  - A glycerol kinase (Gyk) knock-out (KO) mouse model permits improved understanding
      of glycerol kinase (GK) deficiency (GKD) pathogenesis, however, early death of
      affected mice limits its utility. The purpose of this work was to delay death of
      affected males to investigate thoroughly their phenotypes. An adenoviral vector
      carrying the human (Adeno-XGK) or mouse (Adeno-XGyk) GK gene was injected into KO
      mice within 24 h of birth. Adeno-XGK did not change KO mouse survival time
      despite liver GK activity greater than 100% of wild type. However, Adeno-XGyk
      improved KO mouse survival time greater than two-fold. These investigations
      demonstrate that gene replacement therapy for Gyk KO mice is more efficacious
      using murine Gyk than human GK. These studies expand our understanding of GKD
      pathogenesis in the murine model, and show that while murine GKD is more severe
      than in humans, GKD mice have similar metabolic disturbances to affected humans
      with hypoglycemia and acidemia.

PMID- 16105551
TI  - Probing the sweet determinants of brazzein: wild-type brazzein and a tasteless
      variant, brazzein-ins(R18a-I18b), exhibit different pH-dependent NMR chemical
      shifts.
AB  - Brazzein is a small, intensely sweet protein. As a probe of the functional
      properties of its solvent-exposed loop, two residues (Arg-Ile) were inserted
      between Leu18 and Ala19 of brazzein. Psychophysical testing demonstrated that
      this mutant is totally tasteless. NMR chemical shift mapping of differences
      between this mutant and brazzein indicated that residues affected by the
      insertion are localized to the mutated loop, the region of the single alpha
      helix, and around the Cys16-Cys37 disulfide bond. Residues unaffected by this
      mutation included those near the C-terminus and in the loop connecting the alpha
      helix and the second beta-strand. In particular, several residues of brazzein
      previously shown to be essential for its sweetness (His31, Arg33, Glu41, Arg43,
      Asp50, and Tyr54) exhibited negligible chemical shift changes. Moreover, the pH
      dependence of the chemical shifts of His31, Glu41, Asp50, and Tyr54 were
      unaltered by the insertion. The insertion led to large chemical shift and pKa
      perturbation of Glu36, a residue shown previously to be important for brazzein's
      sweetness. These results serve to refine the known sweetness determinants of
      brazzein and lend further support to the idea that the protein interacts with a
      sweet-taste receptor through a multi-site interaction mechanism, as has been
      postulated for brazzein and other sweet proteins (monellin and thaumatin).

PMID- 16105552
TI  - From the anther to the proctodeum: Pear (Pyrus communis) pollen digestion in
      Osmia cornuta larvae.
AB  - Modifications of the pollen grains of Pyrus communis Linneaus that occur during
      the digestion by Osmia cornuta (Latreille) larvae were studied histochemically.
      We compared the features of the pollen grains found in the anthers, in the larval
      cell provisions and in the alimentary canal of the 5th instar larvae.
      Modifications were already evident in the provisions and consisted of protoplast
      protrusions through the apertures and a decrease in the number of starch
      containing pollen grains. After pollen grains were ingested by the larvae, the
      protoplast appeared retracted from the pollen wall. Pollen digestion began in the
      anterior part of the midgut, where we observed: (1) disorganised intine at the
      apertures; (2) disappearance of DAPI staining of nuclear pollen DNA; (3) fewer
      pollen grains containing starch than in the anthers; (4) some empty pollen
      grains. Pollen grains in the proctodeum appeared extremely compressed and
      crushed. Some grains appeared to be unaffected by the digestive process. We
      hypothesise that the protrusion of the intine and of the protoplast from the
      apertures in bee provisions could be considered a kind of pre-treatment necessary
      to initiate the digestion process in the larval alimentary canal.

PMID- 16105553
TI  - Introduction. What's happening with heparin-induced thrombocytopenia: emerging
      preventive, diagnostic, and management strategies.

PMID- 16105554
TI  - Evolving management strategies for heparin-induced thrombocytopenia.
AB  - New treatment strategies based on the availability of alternative anticoagulants
      have improved outcomes for patients with heparin-induced thrombocytopenia (HIT).
      Patients with HIT are at an extreme risk of thrombosis even after the
      discontinuation of heparin. Maintaining a high degree of awareness and
      instituting alternative anticoagulation immediately on suspicion of HIT are the
      two keys to preventing death, limb amputation, and other complications such as
      pulmonary embolism, myocardial infarction, or stroke; stopping heparin alone is
      inadequate. Warfarin should not be used early or unopposed with HIT, and when
      appropriate, transition to warfarin must be done cautiously to avoid venous limb
      gangrene or central skin necrosis. The direct thrombin inhibitors (DTIs)
      lepirudin and argatroban are approved by the US Food and Drug Administration for
      treating HIT and both are effective for improving patient outcomes. Because of
      its favorable pharmacologic characteristics, the DTI bivalirudin has been
      successfully employed in HIT, particularly in patients with multiorgan failure.

PMID- 16105555
TI  - Update on heparin-induced thrombocytopenia and cardiovascular interventions.
AB  - Although heparin/protamine has been the standard anticoagulation regimen in
      cardiac surgery for decades, it induces negative reactions within the
      vasculature. Heparin-induced thrombocytopenia (HIT) is a highly prothrombotic
      immune reaction to heparin that may result in death, limb ischemia leading to
      amputation, graft occlusion, and other severe thrombotic events. Patients
      undergoing cardiac surgery are at high risk for HIT antibody seroconversion and
      at risk for clinical HIT. For patients with acute or subacute HIT and needing
      urgent cardiac surgery, accepted protocols for alternative, non-heparin
      anticoagulation are needed. The direct thrombin inhibitor bivalirudin offers
      promise in this area and is currently being evaluated in multicenter trials as an
      alternative for heparin/protamine in patients with HIT undergoing cardiac
      surgery.

PMID- 16105556
TI  - The heparin-induced thrombocytopenia task force model: implementing quality
      improvement and economic outcome initiatives.
AB  - Heparin-induced thrombocytopenia (HIT) is a costly but potentially preventable
      complication associated with the use of heparin. Based on a 1% to 3% incidence of
      HIT, the total cost and potential financial loss due to HIT complicating open
      heart surgery is estimated to range from over 100 to 300 million dollars and from
      over 33 to 100 million dollars annually, respectively, in the United States. To
      minimize the personal and economic cost of HIT, the Charleston Area Medical
      Center (CAMC) HIT Task Force developed institutional guidelines for diagnosis and
      treatment, educated medical staff and patients, and took measures institution
      wide to reduce patient exposures to heparin.

PMID- 16105557
TI  - The incidence and clinical features of heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is an important adverse reaction of
      heparin therapy that can have catastrophic consequences if overlooked or
      misdiagnosed. Treatment with either unfractionated heparin (UFH) or low-molecular
      weight heparin (LMWH) can trigger this complication. Orthopedic, cardiac, and
      vascular surgery patients exposed to prophylactic or therapeutic doses of heparin
      are at particular risk. Awareness of the clinical features and different
      presentations of HIT are essential for preventing severe morbidity and mortality
      associated with this disease.

PMID- 16105558
TI  - Detection and significance of heparin-platelet factor 4 antibodies.
AB  - Heparin-induced thrombocytopenia (HIT) represents an immune reaction to heparin,
      which if unrecognized and untreated, has the potential for catastrophic
      thrombotic events. The demonstration of antibodies directed against the heparin
      platelet factor 4 (H-PF4) complex is an important component of the diagnosis of
      HIT. Typically, test results are not rapidly available, and the diagnosis
      therefore rests principally on clinical grounds. Nevertheless, the presence of H
      PF4 antibodies provides important confirmation of the diagnosis, and may predict
      for adverse cardiac events even in the absence of HIT. Although more research is
      certainly required, the use of alternative (non-heparin) anticoagulants for
      cardiac surgery and other cardiovascular procedures would substantially reduce
      the incidence of HIT and could possibly improve patient outcomes.

PMID- 16105559
TI  - Antimicrobial activity and pharmacokinetics/pharmacodynamics of the novel
      glycylcycline, tigecycline.

PMID- 16105560
TI  - Pharmacokinetic/pharmacodynamic profile for tigecycline-a new glycylcycline
      antimicrobial agent.
AB  - Tigecycline is a new first-in-class glycylcycline antimicrobial agent with
      expanded broad-spectrum activity against both Gram-negative and Gram-positive
      aerobes and anaerobes, as well as atypical bacterial species. The spectrum of
      activity extends to clinically relevant susceptible and multidrug-resistant
      strains of Staphylococcus aureus, Streptococcus pneumoniae, vancomycin-resistant
      enterococci, and Enterobacteriaceae, including extended-spectrum beta-lactamase
      producing strains. Tigecycline is administered as an intravenous formulation and
      has been studied in the treatment of serious polymicrobial infections, including
      complicated skin and skin-structure infections and intra-abdominal infections.
      Pharmacokinetic analysis of data from phase 1 trials of healthy subjects indicate
      that tigecycline has a large volume of distribution, signifying extensive tissue
      penetration, and a long terminal elimination half-life (approximately 40 h),
      easily allowing for twice-daily dose administration. Tigecycline penetrates well
      into blister fluid, which supports the positive findings of phase 2 and 3 studies
      of the efficacy of tigecycline in the treatment of serious skin and skin
      structure infections. Metabolic studies in humans have revealed that tigecycline
      undergoes very limited metabolism and the primary route of elimination of
      unchanged drug is through the feces, with glucuronidation and renal elimination
      as secondary routes. A preliminary pharmacokinetic (PK)/pharmacodynamic analysis
      in experimental animal models of infection indicates that the efficacy of
      tigecycline is probably best predicted by the ratio of the area under the
      concentration-time curve to the minimum inhibitory concentration. The expanded in
      vitro activity against a broad range of bacteria, including resistant pathogens,
      and favorable PK profile of tigecycline suggest that this novel antimicrobial
      agent should offer clinicians an option for the treatment of patients with
      serious bacterial infections.

PMID- 16105561
TI  - In vitro activity of tigecycline against 3989 Gram-negative and Gram-positive
      clinical isolates from the United States Tigecycline Evaluation and Surveillance
      Trial (TEST Program; 2004).
AB  - The Tigecycline Evaluation and Surveillance Trial (TEST Program) determined the
      in vitro activity of tigecycline over a large population of organisms from
      geographically diverse sites. Tigecycline was compared to amikacin, ampicillin,
      amoxicillin/clavulanic acid, imipenem, cefepime, ceftazidime, ceftriaxone,
      levofloxacin, minocycline, piperacillin/tazobactam, linezolid, penicillin, and
      vancomycin against 3989 commonly encountered clinical Gram-negative and Gram
      positive pathogens collected from sites in the United States during 2004. The
      tigecycline activity was equivalent to imipenem against Enterobacteriaceae.
      Tigecycline inhibited extended-spectrum beta-lactamase and AmpC phenotypes at
      MIC90 values (minimum inhibitory concentration) of < or =2 microg/mL. In vitro
      results for tigecycline were similar to other broad-spectrum antimicrobial agents
      against nonfermenters with MIC90 results of 2 microg/mL against Acinetobacter
      spp. and >16 microg/mL against Pseudomonas aeruginosa. Tigecycline demonstrated
      potent activity against Staphylococcus aureus (MIC90, 0.25 microg/mL) and
      enterococci (MIC90, 0.12 microg/mL) regardless of methicillin or vancomycin
      susceptibility. Tigecycline MIC values were unaffected by penicillin
      nonsusceptibility and beta-lactamase production among fastidious respiratory
      pathogens (Streptococcus pneumoniae [MIC90, 0.5 microg/mL] and Haemophilus
      influenzae [MIC90, 0.25 microg/mL]). Tigecycline offers excellent activity
      against most of the commonly encountered nosocomial and community-acquired
      bacterial pathogens.

PMID- 16105562
TI  - Tigecycline activity tested against 26,474 bloodstream infection isolates: a
      collection from 6 continents.
AB  - The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested
      against recent bloodstream infection (BSI) pathogen isolates from 6 continents.
      Frequency of clinical occurrence of these pathogens was determined and their
      antibiograms assessed using reference broth microdilution methods. A total of
      26474 strains were tested for tigecycline susceptibility according to the
      Clinical and Laboratory Standards Institute (formerly the National Committee for
      Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from
      M100-S15 and the package insert. The rank order of pathogens was Staphylococcus
      aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci
      (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas
      aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%),
      Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%).
      Tigecycline exhibited a broader spectrum of activity against BSI isolates when
      compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams
      (imipenem). Tigecycline was highly active against most pathogens tested,
      including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25
      microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli
      (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter
      spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas
      aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae
      (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of
      antimicrobial potency versus BSI isolates collected worldwide. Serious infections
      in nosocomial environments should benefit from tigecycline use among the
      investigational phase 3 agents focused toward resistant strains.

PMID- 16105563
TI  - Antimicrobial activity of tigecycline tested against organisms causing community
      acquired respiratory tract infection and nosocomial pneumonia.
AB  - Emerging antimicrobial resistance among respiratory tract pathogens has created a
      critical need for development of new antimicrobial agents that are not affected
      by the commonly occurring genetic resistance mechanisms. Tigecycline, a novel
      broad-spectrum parenteral glycylcycline, has been shown to be active against many
      of Gram-positive, Gram-negative, atypical, and anaerobic organisms, including
      strains highly resistant to commonly prescribed antimicrobials and was recently
      approved by the US Food and Drug Administration for treating infections of skin
      and skin structures, and for intra-abdominal infections. In this study,
      tigecycline spectrum and potency were evaluated against a global collection of
      pathogens (2000-2004) recovered from community-acquired respiratory infections
      (7580 strains) or from hospitalized patients with pneumonia (3183 strains). Among
      community-acquired infections, the ranking pathogens were Haemophilus influenzae
      (52.9%; 21% ampicillin-resistant), Streptococcus pneumoniae (39.2%; 23.7%
      penicillin-nonsusceptible), and Moraxella catarrhalis (7.9%). Tigecycline
      displayed potent activity by inhibiting 100% of the 3 species at clinically
      achievable concentrations (2, 1, and 0.5 microg/mL, respectively). The 10 most
      prevalent pathogens producing 94.3% of pneumonias in hospitalized patients were
      Staphylococcus aureus (48.5% of strains; 49.4% oxacillin-resistant), Pseudomonas
      aeruginosa (15.6%), Klebsiella spp. (5.6%), S. pneumoniae (4.6%), Acinetobacter
      spp. (4.5%), Enterobacter spp. (4.0%), Escherichia coli (3.8%), Serratia
      marcescens (2.5%), Enterococcus spp. (2.3%), Stenotrophomonas maltophilia (1.8%),
      and beta-hemolytic streptococci (1.1%). At a concentration of 4 microg/mL,
      tigecycline inhibited >96% of these pathogens (exception, P. aeruginosa). S.
      aureus was readily inhibited by tigecycline (MIC50 and MIC90, 0.25 and 0.5
      microg/mL, respectively) with all strains inhibited at < or =1 microg/mL.
      Streptococci recovered from hospitalized patients (beta-hemolytic and S.
      pneumoniae) were also very susceptible to tigecycline with the highest MIC being
      0.12 microg/mL. All E. coli (including 13.3% with an extended-spectrum beta
      lactamase [ESBL] phenotype) were inhibited by < or =1 microg/mL, and all
      Klebsiella (25.8% ESBL phenotype) and Enterobacter spp. plus 97.0% of Serratia
      spp. were inhibited by < or =4 microg/mL. Tigecycline was also active against
      Acinetobacter spp. and S. maltophilia strains (MIC50 and MIC90, 1 and 4
      microg/mL, respectively). Further clinical studies should consider the role that
      tigecycline may play in the therapy for severe respiratory tract infections, both
      of nosocomial and community origin.

PMID- 16105564
TI  - Potency and spectrum of tigecycline tested against an international collection of
      bacterial pathogens associated with skin and soft tissue infections (2000-2004).
AB  - The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated
      against 5289 bacterial isolates recovered from hospitalized patients with skin
      and soft tissue infections during 2000-2004. Strains were submitted from >70
      medical centers in North America, Latin America, and Europe, and were tested
      centrally using reference broth microdilution methods. The top 10 ranking
      pathogens (95% of total) recovered included Staphylococcus aureus (55.2%),
      Enterococcus spp. (9.6%), Pseudomonas aeruginosa (6.4%), Escherichia coli (5.6%),
      beta-hemolytic streptococci (5.0%), coagulase-negative staphylococci (4.9%),
      Enterobacter spp. (2.8%), Klebsiella spp. (2.6%), Proteus mirabilis (1.7%), and
      indole-positive Proteae (1.2%). All staphylococci (S. aureus and coagulase
      negative staphylococci), enterococci, beta-hemolytic streptococci, viridans group
      streptococci, and E. coli were inhibited by < or =2 microg/mL of tigecycline; in
      addition, 97% of Klebsiella spp., 95% of Enterobacter spp., and 97% of
      Acinetobacter spp. were inhibited at this concentration. Only P. aeruginosa and
      all Proteae (MIC90, 16 microg/mL) displayed elevated MIC values to tigecycline.
      The broad spectrum of activity exhibited by this glycylcycline included
      tetracycline-resistant organism subsets, as well as oxacillin-resistant S.
      aureus, vancomycin-resistant enterococci, and extended-spectrum beta-lactamase
      producing enteric bacilli strains. Tigecycline represents a new choice among
      broad-spectrum parenteral agents for the common Gram-positive and -negative
      pathogens producing serious infections of skin and soft tissues.

PMID- 16105565
TI  - Antimicrobial activity of tigecycline tested against nosocomial bacterial
      pathogens from patients hospitalized in the intensive care unit.
AB  - The antimicrobial activity of tigecycline and selected antimicrobials was
      evaluated against bacterial pathogens isolated from patients hospitalized in
      intensive care units (ICUs) worldwide. A total of 9093 isolates were
      consecutively collected in >70 medical centers in North America (4157), South
      America (1830), Europe (3034), and the Asia-Australia (72) areas. The isolates
      were collected from the bloodstream (68.5%), respiratory tract (13.6%), skin/soft
      tissue (5.5%), and urinary tract (2.0%) infections in the 2000-2004 period, and
      susceptibility was tested by reference broth microdilution methods. The most
      frequently isolated pathogens were Staphylococcus aureus (32.1%), Enterococcus
      spp. (13.7%), coagulase-negative staphylococci (CoNS; 13.0%), Pseudomonas
      aeruginosa (8.4%), and Escherichia coli (7.9%). All Gram-positive pathogens
      (5665) were inhibited at < or =1 microg/mL of tigecycline. Resistance to
      oxacillin was detected in 43.5% of Staphylococcus aureus and in 85.0% of CoNS,
      and resistance to vancomycin was observed in 18.6% of enterococci. Tigecycline
      was very active against Enterobacteriaceae (1876 strains tested) with an MIC90 of
      < or =1 microg/mL, except for Serratia spp. (2 microg/mL). Extended-spectrum beta
      lactamase (ESBL) phenotype was detected in 10% of E. coli and 31% of Klebsiella
      spp., whereas 28% of Enterobacter spp. were resistant to ceftazidime (AmpC enzyme
      production). These resistance phenotypes did not adversely affect tigecycline
      activity. Tigecycline and trimethoprim/sulfamethoxazole were the most active
      compounds against Stenotrophomonas maltophilia (MIC90, 2 and 1 microg/mL
      respectively). Tigecycline was also active against Acinetobacter spp. (MIC90, 1
      microg/mL), but P. aeruginosa showed decreased susceptibility to tigecycline
      (MIC90, 16 microg/mL). In summary, isolates from ICU patients worldwide showed
      high rates of antimicrobial resistance. The most alarming problems detected were
      vancomycin resistance among enterococci, ESBL-mediated beta-lactam resistance and
      fluoroquinolone resistance among Enterobacteriaceae, and carbapenem resistance
      among P. aeruginosa and Acinetobacter spp. Tigecycline exhibited potent in vitro
      activity against most of clinically important pathogenic bacteria (except P.
      aeruginosa) isolated from ICU patients and may represent an excellent option for
      the treatment of infections in this clinical environment.

PMID- 16105566
TI  - Activity of tigecycline tested against a global collection of Enterobacteriaceae,
      including tetracycline-resistant isolates.
AB  - Steadily increasing resistance among the Enterobacteriaceae to beta-lactams,
      fluoroquinolones, aminoglycosides, tetracyclines, and
      trimethoprim/sulfamethoxazole has compromised the utility of these commonly used
      antimicrobial classes for many community- or hospital-acquired infections. The
      development of tigecycline, the sentinel representative of a novel class of broad
      spectrum agents (the glycylcyclines), represents an important milestone in
      addressing this critical need. Resistance to tigecycline might be expected to
      occur via the same mechanisms that produce tetracycline resistance; however,
      tigecycline remains stable and largely unaffected by the commonly occurring
      efflux and ribosomal protection resistance mechanisms. In this study, an
      international collection of Enterobacteriaceae (11327 isolates; 32.8%
      tetracycline-resistant) from global surveillance studies (2000-2004) were
      evaluated against tigecycline and other comparator antimicrobials. Although the
      most active agents were the carbapenems and aminoglycosides (97.5-99.7%
      susceptible), tigecycline displayed high potency (MIC50 and MIC90, 0.25 and 1
      microg/mL) with 95.7% of all strains being inhibited at < or =2 microg/mL.
      Despite higher MIC values observed with Serratia spp. and Proteae, between 90.5%
      and 97.5% of isolates were inhibited by < or =4 microg/mL of tigecycline.
      Tetracycline-resistant populations demonstrated only modest decreases in potency
      to tigecycline, which appeared to be species-dependent (up to 2-fold only for
      Escherichia coli, Salmonella spp., Shigella spp., and Panteoa agglomerans; and up
      to 4-fold for Klebsiella spp., Enterobacter spp., and Citrobacter spp.). Among E.
      coli (263 isolates) and Klebsiella spp. (356) that meet recognized screening
      definitions for extended-spectrum beta-lactamase production, 100.0% and 94.4%
      were inhibited by tigecycline at 2 microg/mL, respectively. These findings
      confirm that tigecycline exhibits potency, breadth of spectrum, and stability to
      the commonly occurring resistance mechanisms found in contemporary
      Enterobacteriaceae isolates, attributes that make this parenteral agent an
      attractive candidate for use against serious infections produced by these
      species.

PMID- 16105567
TI  - In vitro activity of tigecycline against 6792 Gram-negative and Gram-positive
      clinical isolates from the global Tigecycline Evaluation and Surveillance Trial
      (TEST Program, 2004).
AB  - Tigecycline, a new glycylcycline antibiotic, has shown promising in vitro
      activity against many common pathogens, including multidrug-resistant strains. To
      determine the activity of tigecycline against a broad range of pathogens from
      diverse populations and geographic areas, the Tigecycline Evaluation and
      Surveillance Trial (TEST Program) commenced in 2003. This study evaluated the
      activity of tigecycline and commonly used antimicrobials against 6792 clinical
      isolates from 40 study centers in 11 countries. Tigecycline was the most active
      agent tested against Gram-positive facultative species including multidrug
      resistant strains. MIC90 results (microg/mL) for tigecycline against Enterococcus
      faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae,
      and Streptococcus pneumoniae were 0.12, 0.12, 0.25, and 0.25 microg/mL,
      respectively. Tigecycline was active against Enterobacteriaceae with an MIC90 of
      1 microg/mL. Haemophilus influenzae was very susceptible to tigecycline with an
      MIC90 of only 0.25 microg/mL. Pseudomonas aeruginosa was the least susceptible
      organism tested against tigecycline. Tigecycline appears to be a promising new
      glycylcycline agent for the treatment of many types of pathogens with varying
      resistance phenotypes.

PMID- 16105568
TI  - Reevaluation of Enterobacteriaceae MIC/disk diffusion zone diameter regression
      scattergrams for 9 beta-lactams: adjustments of breakpoints for strains producing
      extended spectrum beta-lactamases.
AB  - Validity of the current susceptibility breakpoint criteria for 9 beta-lactam
      antimicrobials and performance of proposed alternative breakpoints to improve
      prediction of clinical outcomes were analyzed by testing a contemporary
      collection of 350 Enterobacteriaceae, enriched for an overrepresentative
      collection of 70 (20.0%) strains producing extended-spectrum beta-lactamases
      (ESBLs). The majority of the strains were isolated from bloodstream infections
      (83.7% of the entire collection and 85.7% of the ESBL subset). The 9 beta-lactam
      antimicrobials analyzed were aztreonam, cefepime, cefotaxime, cefotetan,
      cefoxitin, ceftazidime, ceftriaxone, ceftizoxime, and cefuroxime. Reference broth
      microdilution MIC results were compared with those zone diameters obtained by the
      standardized disk diffusion test. The correlation coefficient (r) was acceptable
      for all antimicrobials, ranging from 0.87 (cefotetan) to 0.97 (aztreonam,
      cefotaxime, and ceftazidime). Using the current susceptible breakpoint criteria
      for Enterobacteriaceae, the intermethod categorical agreement ranged from 90.6%
      (cefotaxime) to 98.0% (ceftazidime). Very major (false-susceptible by disk test)
      and major errors (false-resistant) were nil (0.0%) for 6 of the 9 beta-lactams.
      Minor error rates ranged from only 0.9% (cefotetan) to 9.4% (cefotaxime). The
      proposed MIC breakpoint criteria (generally lower) adjusted to levels to
      accurately detect ESBL-producing strains and better predict clinical outcomes,
      also had acceptable intermethod concordance ranging from 90.6% (cefotetan) to
      100.0% (ceftazidime). Remarkably, an improvement in the intermethod categorical
      agreement ranging from +1.7% to +8.3% was observed for 7 of the 9 antimicrobials,
      including the ESBL index or screening compounds (aztreonam, ceftazidime,
      cefotaxime, and ceftriaxone). No change in the breakpoint criteria, with removal
      of the intermediate category was tentatively proposed for cefoxitin and
      cefuroxime, resulting in an increase of the serious intermethod errors (very
      major and major), but the absolute intermethod agreement remained highly
      acceptable at 90.6% to 93.4%. Although the current breakpoint criteria remain
      acceptable in minimizing intermethod discords, the alternative susceptible
      breakpoint criteria proposed by combining pharmacokinetic/pharmacodynamic
      (PK/PD), microbiology MIC population analyses, and clinical success parameters
      possess improved intermethod agreement for the ESBL screening drugs and 5 other
      broad-spectrum beta-lactam compounds. The Clinical Laboratory Standards Institute
      (formerly, the National Committee for Clinical Laboratory Standards) should
      consider these changes to facilitate the detection of all Enterobacteriaceae with
      low PK/PD target attainment rates, therefore having the potential for suboptimal
      responses with usual therapeutic dosing.

PMID- 16105569
TI  - Potency and spectrum trends for cefepime tested against 65746 clinical bacterial
      isolates collected in North American medical centers: results from the SENTRY
      Antimicrobial Surveillance Program (1998-2003).
AB  - We evaluated the antimicrobial spectrum and potency of cefepime and selected
      comparators agents against clinical bacterial strains collected in North America
      over a 6-year period (1998-2003). Isolates were consecutively collected from
      bloodstream (44%), respiratory tract (41%), urinary tract (6%), and skin/soft
      tissue (5%) infections in 48 medical centers. Isolates were susceptibility tested
      by reference broth microdilution methods in a central laboratory. Oxacillin
      resistant staphylococci and enterococci were excluded from the analysis. Imipenem
      (MIC90 = 1 microg/mL, 99.9% susceptible) was the most active compound tested
      against Enterobacteriaceae (22860 isolates tested) followed by cefepime (MIC90 =
      0.25 microg/mL, 99.5% susceptible) > amikacin (99.4% susceptible) > ceftriaxone
      (95.6% susceptible) > aztreonam (95.1% susceptible). Among comparators, the
      lowest susceptibility rate for Enterobacteriaceae was observed with ciprofloxacin
      (92.8% susceptible). Imipenem was also the most active compound against ESBL
      producing Klebsiella spp. and Escherichia coli (99.3% and 100% susceptible,
      respectively), followed by amikacin (81.4% and 97.2% susceptible, respectively)
      and cefepime (92.5% and 93.8% susceptible, respectively). Cefepime activity
      against Pseudomonas aeruginosa (85.2% susceptible) was similar to that of
      imipenem (86.9% susceptible). Against oxacillin-susceptible Staphylococcus
      aureus, cefepime (MIC90 = 4 microg/mL, 100.0% susceptible) was 4-fold more active
      than ceftazidime (MIC90 = 16 microg/mL, 86.4% susceptible) and showed a higher
      susceptibility rate than ciprofloxacin (93.2% susceptible). Cefepime was the most
      active compound tested against Streptococcus pneumoniae (MIC90 = 1 microg/mL,
      97.4% susceptible), ranked after gatifloxacin and levofloxacin (99.2%
      susceptible). The activity of cefepime remained stable during the study period
      evaluated with the susceptibility rates varying from 99.3% to 99.8% among the
      Enterobacteriaceae and 84.4% to 88.4% among P. aeruginosa isolates. In summary,
      cefepime has retained broad activity and spectrum against Enterobacteriaceae, P.
      aeruginosa, and Gram-positive cocci (except oxacillin-resistant staphylococci and
      enterococci) isolated from North American medical centers in the 1998-2003
      period. Continued resistance surveillance is critical to monitor the
      effectiveness of widely used parenteral antimicrobial agents such as cefepime.

PMID- 16105570
TI  - A vision of our own.

PMID- 16105572
TI  - Multifocal IOLs for presbyopia.

PMID- 16105573
TI  - Determining scotopic pupil size.

PMID- 16105575
TI  - Determining scotopic pupil size.

PMID- 16105576
TI  - Binocular vision impairment after refractive surgery.

PMID- 16105579
TI  - Retinal thickness measurement after phacoemulsification.

PMID- 16105581
TI  - Assessment of systems of analyzing PCO.

PMID- 16105583
TI  - Management of lens-iris diaphragm retropulsion syndrome.

PMID- 16105584
TI  - Contraindication to capsule staining.

PMID- 16105585
TI  - Management of lens-iris diaphragm retropulsion syndrome.

PMID- 16105588
TI  - Management of lens-iris diaphragm retropulsion syndrome.

PMID- 16105589
TI  - Consultation section: cataract surgical problem.

PMID- 16105594
TI  - Intraoperative Healon5 injection into blebs for small conjunctival breaks created
      during trabeculectomy.
AB  - Leakage from a conjunctival break created during trabeculectomy may cause serious
      complications such as shallow anterior chamber, hypotony, and a flat bleb in the
      early postoperative period. Therefore, careful handling of the conjunctiva with a
      nontoothed forceps is essential. However, thin conjunctiva is susceptible to
      mechanical injury and is difficult to repair with suturing, especially when the
      point of leakage is close to the scleral flap. In 3 consecutive cases in which a
      small break in the thin conjunctiva adjacent to the scleral flap was created
      during trabeculectomy, sodium hyaluronate 2.3% (Healon5) was intraoperatively
      injected into the bleb. The break was successfully closed with an intraoperative
      injection of Healon5 into the bleb. This procedure appears to be a simple, safe,
      and effective method for closure of a small conjunctival break.

PMID- 16105595
TI  - Intralenticular bimanual irrigation: aspiration for subluxated lens in Marfan's
      syndrome.
AB  - We describe a new technique of aspiration of subluxated lens in young patients
      with Marfan's syndrome. Two small circular anterior capsulorhexis (1.5 mm to 2.0
      mm) openings were created, and bimanual irrigation/aspiration was performed by
      introducing the irrigation cannula through 1 capsular opening and the aspiration
      cannula through the other. The irrigation cannula served the dual purpose of
      hydrating the lens matter and holding the lens in central position to ensure
      complete aspiration of the lens matter. The lens capsule was later removed and
      anterior vitrectomy performed by a vitrectomy cutter. This new technique of
      intralenticular irrigation/aspiration is effective and safe in performing lens
      aspiration in extensively dislocated crystalline lens in Marfan's syndrome.

PMID- 16105596
TI  - Device for simulating anterior segment surgery.
AB  - To provide a more realistic method for practicing anterior segment surgery, a
      device was designed that incorporates aspects of currently available cadaver
      globe fixation methods. A Styrofoam head was fitted with a funnel and tubing
      system that allows for direct application of variable external suction to a globe
      placed in an artificial socket. Prototypes were tested in a wet lab environment,
      which demonstrated that this method provides reliable globe fixation and allows
      for variable control of intraocular pressure during a variety of anterior and
      posterior segment surgical techniques.

PMID- 16105597
TI  - Pilocarpine-induced shift of an accommodating intraocular lens: AT-45 Crystalens.
AB  - PURPOSE: To measure the shift of an accommodating plate-haptic intraocular lens
      (IOL) along the visual axis induced by ciliary muscle contraction after
      application of pilocarpine. SETTING: Department of Ophthalmology, Medical
      University of Vienna, Vienna, Austria. METHODS: Fifty-four eyes of 28 patients
      with age-related cataract comprised this prospective study. Each patient received
      an AT-45 silicone accommodating IOL (Crystalens, Eyeonics Corp.) after
      standardized cataract surgery. In a subgroup of 24 eyes, capsular bag fibrosis
      was reduced by extensive polishing of the anterior capsule with a slit cannula.
      Assessment included measurements of anterior chamber depth, assessed with partial
      coherence interferometry, before and after application of pilocarpine 2% and
      evaluation of near visual acuity 1 month and 3 months postoperatively. RESULTS: A
      slight backward shift of the IOL of 151 mum in the nonpolished group (P < .001)
      and 122 mum in the polished group (P < .005) could be detected after application
      of pilocarpine. Polishing the capsule did not influence IOL shift. The median
      near visual acuity with distance correction 1 month and 3 months postoperatively
      was J5 and J4, respectively, in the nonpolished group and J6 at both times in the
      polished group. CONCLUSIONS: Pilocarpine induced a counterproductive active
      backward shift of the AT-45 IOL. Polishing of the capsular bag had no impact on
      accommodative ability. The reading performance of patients with the AT-45 IOL
      patients at 1 and 3 months was not significantly different from that of with a
      standard IOL under similar testing methods.

PMID- 16105598
TI  - Drug-induced intraocular lens movement and near visual acuity after AcrySof
      intraocular lens implantation.
AB  - PURPOSE: To evaluate the factors influencing AcrySof intraocular lens (IOL)
      (Alcon Laboratories) movement and near visual acuity after cyclopentolate 1% and
      pilocarpine 2%. SETTING: Department of Ophthalmology, University of Ankara,
      Ankara, Turkey. METHODS: Thirty eyes of 22 patients with AcrySof IOL implantation
      were included in this prospective study. Near visual acuity (Jaeger) at 35 cm
      through best distance correction without an add and pupil diameter were measured
      and correlated with anterior chamber depth (ACD) measured with ultrasound
      biomicroscopy (UBM) after application of cyclopentolate 1% and pilocarpine 2%,
      respectively. The magnitude of the change in the ACD was correlated with the
      accommodation amplitude, patient age, time interval between surgery and imaging,
      preoperative axial length, capsulorhexis diameter, ACD during cycloplegia, IOL
      diameter, and presence of posterior capsule opacification (PCO). RESULTS: Near
      visual acuity significantly decreased after application of cyclopentolate 1% and
      increased after application of pilocarpine 2% (P < .001) in all eyes. The IOL
      moved anteriorly in 8 (26%) eyes and posteriorly in 22 (74%) eyes after
      pilocarpine 2%. There was no correlation between the ACD and near visual acuity
      under cyclopentolate 1% (r = 0.06, P > .05) or pilocarpine 2% (r = 0.04, P >
      .05). There was a moderate correlation between the anterior IOL movement and
      accommodation amplitude (P < .05, r = 0.42). There was no correlation between the
      magnitude of the IOL movement and patient age, time interval between surgery and
      imaging, the preoperative axial length, capsulorhexis diameter, ACD during
      cycloplegia, IOL diameter, and the presence of PCO (P > .05). CONCLUSIONS: There
      was better near visual acuity in all eyes with the AcrySof MAIOL, although most
      IOLs move slightly backward after of pilocarpine 2%. This points out
      pseudoaccommodation rather than pseudophakic accommodation. Ultrasound
      biomicroscopy is useful in determining the ACD and the relation between the IOL
      and the surrounding tissues after cataract surgery.

PMID- 16105599
TI  - Systematic evaluation of wavefront-guided outcomes.
AB  - PURPOSE: To present a format for reporting outcomes of aberrometer-guided
      refractive procedures. SETTING: SurgiVision Consultants, Inc., Scottsdale,
      Arizona, and Food and Drug Administration, Center for Devices and Radiological
      Health, Rockland, Maryland, USA. METHODS: Reports of standard refractive and
      visual outcomes (uncorrected visual acuity, manifest refractive spherical
      equivalent, best spectacle-corrected visual acuity) should be provided for any
      refractive surgery report. Comparison of postoperative uncorrected visual acuity
      to preoperative best spectacle-corrected visual acuity should be included.
      Aberration reports should convert 2nd-order terms to refractions (measured in
      diopters) and use standard refractive reporting methods. Changes in coma,
      spherical aberration, and root-mean-square changes should be described using
      statistical methods for aggregate data. Underlying statistics should be reported.
      RESULTS: Aberration changes are well described by the mean error of the attempted
      versus achieved outcomes, comparison of the mean changes, and stability over
      time. Ancillary plots include histogram representation of the postoperative
      scores. Additional reports of visual function should be included, as appropriate.
      CONCLUSION: Use of standardized tables and graphs permits qualitative and
      quantitative comparison of outcomes of refractive treatment with wavefront-guided
      lasers. Modifications of the recommended formats can be expected over time.

PMID- 16105600
TI  - Comparison of postoperative pain in patients following photorefractive
      keratectomy versus advanced surface ablation.
AB  - PURPOSE: To compare postoperative pain associated with advanced surface ablation
      versus traditional photorefractive keratectomy (PRK). SETTING: Codet-Aris Vision
      Institute, Tijuana, Mexico. METHODS: This prospective double-masked randomized
      study included 56 eyes of 28 myopic patients who received traditional PRK in 1
      eye and advanced surface ablation in the contralateral eye. For advanced surface
      ablation, removal of corneal epithelium was performed by incubating the cornea
      with 18% ethanol. Subsequently, the epithelium was removed by a surgical
      microsponge. For eyes treated by PRK, mechanical debridement of corneal
      epithelium was performed with a surgical blade. Excimer laser corneal ablation
      was performed using the Nidek EC-5000 excimer laser in all eyes. On postoperative
      days 1 and 3, patients were instructed to rate their pain via 3 pain measuring
      tools: (1) a global subjective rating; (2) a 100 mm visual analog scale (VAS);
      and (3) an 11-point numerical rating scale. RESULTS: All 28 patients completed
      postoperative questionnaires on day 1 and day 3. On postoperative day 1, all
      reported pain in both eyes. Using the global assessment rating, patients reported
      statistically significant more pain in eyes treated by advanced surface ablation
      (P = .0037; confidence interval [CI], 59%-92%). Furthermore, based on the 11
      point numerical rating scale, mean pain scores were significantly higher in the
      advanced surface ablation treated eyes (P = .0121), while the VAS mean pain
      scores were marginally significantly higher (P = .0822). On postoperative day 3,
      23 patients reported the presence of some pain, at least in 1 eye. Using the
      global assessment rating, 70% of the those who had pain reported more pain in the
      advanced surface ablation-treated eye (advanced surface ablation 16/23 versus PRK
      7/23) (P = .0931; 95% CI, 47%-87%). In addition, on postoperative day 3, advanced
      surface ablation-treated eyes demonstrated slightly higher mean pain scores based
      on the 11-point numerical rating scale and on the VAS; however, mean differences
      were not statistically significant (P = .3494 and P = .3337, respectively).
      CONCLUSIONS: Advanced surface ablation was associated with statistically
      significantly more postoperative pain than PRK on postoperative day 1. A greater
      percentage of patients reported more pain in the advanced surface ablation
      treated eyes on day 3. Refractive surgeons should consider the postoperative pain
      associated with advanced surface ablation when deciding on the type of epithelial
      debridement for their patients.

PMID- 16105601
TI  - Late dislocation of scleral-sutured posterior chamber intraocular lenses.
AB  - PURPOSE: To examine a recent series of late scleral-sutured posterior chamber
      intraocular lens (PCIOL) dislocations to identify possible causes and preventive
      measures. SETTING: Price Vision Group, Indianapolis, Indiana, USA. METHODS: In
      this retrospective non-comparative interventional case series, 5 consecutive
      patients received treatment for dislocated scleral-sutured PCIOLs between July
      2002 and March 2004. Dislocated lenses were resutured or replaced with another
      scleral-sutured PCIOL. RESULTS: Dislocation of scleral-sutured PCIOLs occurred 7
      to 14 years after implantation. Four dislocations were spontaneous, and 1 was
      precipitated by trauma. In each case, the suture affixing 1 or both haptics
      failed. There was no evidence that the suture had eroded through the tissue or
      that the knot had untied. Microscopic analysis of an explanted IOL with remnants
      of the suture attached showed localized degradation and cracking of the
      polypropylene suture material where it had been embedded in the scleral tissue.
      CONCLUSION: Suture-fixated PCIOLs can dislocate due to degradation of the suture
      material over time. The use of larger diameter (9-0 instead of 10-0)
      polypropylene suture material and placement of the haptic and sutures in the
      ciliary sulcus to promote attachment of scar tissue may enhance the long-term
      stability of scleral-fixated PCIOLs.

PMID- 16105602
TI  - Prospective evaluation of phacoemulsification in adults younger than 50 years.
AB  - PURPOSE: To evaluate intraoperative performance and long-term outcome of
      phacoemulsification in patients younger than 50 years. SETTING: Iladevi cataract
      and IOL Research Centre, Ahmedabad, India. METHODS: A prospective observational
      study was conducted comprising 54 patients (35 men and 19 women) under age 50 who
      had phacoemulsification. Preoperative evaluation included specular microscopy.
      Phacoemulsification with implantation of an AcrySof MA30BA intraocular lens (IOL)
      was performed. Intraoperatively, peripheral extension of capsulorhexis,
      intraoperative posterior capsule opacification (PCO; plaque), and serious
      complications (eg, posterior capsule rupture, vitreous loss) were noted.
      Postoperatively, endothelial cell loss, postoperative PCO, neodymium:YAG (Nd:YAG)
      laser posterior capsulotomy rate, and best corrected visual acuity (BCVA) were
      assessed for 3 years. Patients with intraoperative PCO were analyzed separately.
      RESULTS: Mean patient age was 42.7 years +/- 5.2 SD (men) and 43.1 +/- 3.25 years
      (women). Continuous curvilinear capsulorhexis was achieved in 49 patients
      (90.7%). Intraoperative PCO was present in 14 (25.92%) patients. An Nd:YAG laser
      posterior capsulotomy was performed in 4 patients (28.5%). Posterior capsule
      rupture leading to vitreous loss occurred in 1 patient (1.85%). At 3-year follow
      up, endothelial cell loss was 5.9%. Postoperative PCO developed in 8 patients
      (22.2%), and Nd:YAG laser posterior capsulotomy was performed in 5 patients
      (13.8%). The BCVA was > or = 20/40 in 47 patients (94%). CONCLUSION: Young
      patients pose a challenge in creating a capsulorhexis and display significant
      incidence of intraoperative and postoperative PCO.

PMID- 16105603
TI  - Refractive outcomes of laser in situ keratomileusis after flap complications.
AB  - PURPOSE: To study the refractive and visual outcomes, including surgically
      induced astigmatism, of laser in situ keratomileusis (LASIK) after flap
      buttonholes and incomplete flaps. SETTING: Rajendra Prasad Center for Ophthalmic
      Sciences, All India Institute of Medical Sciences, New Delhi, India. METHODS:
      This was a retrospective case series of 15 patients (15 eyes) who had LASIK after
      flap complications (6 eyes with buttonholes and 9 with incomplete flaps). The
      second surgery was performed after the refraction was stable for 2 months. The
      refractive and visual outcomes were studied. RESULTS: After the flap
      complication, the spheroequivalent did not change significantly (P = .78) but the
      mean pachymetry changed from 523.6 microm +/- 23.14 (SD) to 530.4 +/- 23.96
      microm (P = .04) and the mean absolute cylinder changed from 0.63 +/- 1.01
      diopter (D) to 0.88 +/- 0.87 D (P = .026). The second surgery was performed at a
      mean interval of 6.2 months (range 3 to 17 months). Two eyes had flap
      complications (irregular flaps) again after the second surgery. At the 6-month
      follow-up, the mean spheroequivalent was -0.34 +/- 0.65 D and the mean cylinder
      was 0.15 +/- 0.19 D x 83.6. Thirteen eyes (86.66%) were within 0.5 D of the
      attempted correction. Post-LASIK complications included diffuse lamellar
      keratitis (1 eye), epithelial ingrowth (1 eye), and flap striae (2 eyes). After
      the flap complication, no eye lost 2 or more lines of best spectacle-corrected
      visual acuity (BSCVA); but after the second surgery at 6 months, 1 eye had lost 2
      lines of BSCVA. Six months postoperatively, all eyes had a BSCVA of 20/40 or
      better. CONCLUSION: Laser in situ keratomileusis after flap complications is
      associated with good refractive and visual outcomes; however, there is a higher
      risk for intraoperative and postoperative complications after the second surgery.

PMID- 16105604
TI  - Clinical application of the lens haptic plane concept with transformed axial
      lengths.
AB  - PURPOSE: To clinically evaluate the lens haptic plane (LHP) concept in
      combination with thick-lens ray tracing for intraocular lens (IOL) power
      calculation. SETTING: St. Erik's Eye Hospital, Stockholm, Sweden. METHODS:
      Prospective study of normal cataract cases implanted with Pharmacia CeeOn 809C
      IOL. Axial length was measured by A-scan. The measured value was first
      transformed by addition of a constant value to correct for systematic error.
      Using the transformed axial length and corneal radius measured by keratometry,
      the LHP position was determined. Knowing the IOL design and the power implanted,
      expected refractive outcome was calculated and compared to manifest refraction at
      6 weeks in terms of mean absolute error (MAE). Thick-lens ray tracing in the
      paraxial limit was used for the optical calculation. RESULTS: The mean
      transformed axial length was 23.87 mm. An LHP position algorithm in linear terms
      of transformed axial length and corneal radius gave an MAE of 0.38 D. There was
      no trend with axial length. On the present data, the Holladay 1, Hoffer Q, and
      SRK/T formulas produced MAEs of 0.39 D, 0.39 D, and 0.41 D, respectively, with
      optimized formula constants. The differences were not statistically significant
      (P > .05). CONCLUSIONS: The LHP concept in combination with thick-lens ray
      tracing achieved MAE comparable to that with currently used formulas. The lack of
      trend with axial length is important for patients with short and long eyes.

PMID- 16105605
TI  - Calibration of axial length measurements with the Zeiss IOLMaster.
AB  - PURPOSE: To study the conditions for consistent axial length measurements with
      partial coherence interferometry (PCI) performed with the Zeiss IOLMaster.
      SETTING: University Eye Clinic, Aarhus, Denmark. METHODS: A consecutive,
      unselected series of 1289 cataractous eyes were measured with the optical
      technique of PCI according to the IOLMaster as well as with conventional
      (contact) A-scan ultrasound (US) for the measurement of axial length. For each
      PCI reading, the signal-to-noise ratio (SNR) was recorded and used for comparison
      with the US measurement. All patients had routine phacoemulsification with
      implantation of an intraocular lens (IOL). In 284 cases, the patients were
      reexamined 2 to 3 months after surgery and the axial length was again measured
      using PCI. The readings of the IOLMaster, which had been calibrated against
      immersion US from the manufacturer, were recalculated to represent the true
      optical length and used in the analysis of the consistency of the measurements.
      RESULTS: Not all readings obtainable with the IOLMaster were of good quality, and
      large differences with conventional US were found. The error between US and PCI
      decreased significantly with increasing SNR, showing a minimum error at an SNR
      value above 2.1. The SNR correlated significantly with the visual acuity with
      considerable scatter, however. Excluding readings with a poor quality (SNR <2.1),
      the postoperative PCI measurements showed a high correlation with the
      preoperative measurement (r = 0.99), showing a mean difference of 0.08 mm +/-
      0.12 (SD). The difference was highly significantly different than zero (P < .001)
      and may be explained by a higher refractive index of the biological lens than
      assumed in the original calibration of the IOLMaster. CONCLUSIONS: The quality of
      the axial length readings of the IOLMaster was influenced by the SNR value.
      However, with proper SNR evaluation and recalibration of the PCI measurements, it
      is possible to achieve consistent PCI readings with little variation between
      preoperative and postoperative measurements. These results are promising for a
      higher accuracy of the IOL power calculation.

PMID- 16105606
TI  - Preoperative assessment of secondary intraocular lens implantation for aphakia: a
      comparison of 2 techniques.
AB  - PURPOSE: To compare the preoperative evaluation of secondary intraocular lens
      (IOL) implantation in aphakic adults following cataract extraction in childhood
      using slitlamp examination and high-frequency ultrasound (HFU). METHODS: In a
      prospective case series, patients who had had lensectomies for congenital
      cataracts without primary implantation IOL were evaluated for secondary IOL
      insertion. Slitlamp examination and HFU were performed to study the degree of
      ciliary sulcus support and iridocapsular adhesions. The choice of IOL (posterior
      sulcus supported or anterior chamber) was compared using the 2 techniques.
      RESULTS: Nine eyes of 5 patients (3 men and 2 women aged 15 to 40 years) were
      assessed for secondary IOL insertion. Clinical slitlamp examination suggested
      that 3 of 9 eyes had inadequate sulcociliary support, but HFU of these eyes
      revealed more than adequate capsular remnants. In all 9 eyes, sulcus-supported
      posterior chamber IOLs were implanted. No postoperative complications were
      observed, and no patients required surgery for dislocated IOL. CONCLUSIONS: High
      frequency ultrasound is a useful adjunct for the preoperative assessment of
      secondary ciliary sulcus-supported IOL implantation in aphakic patients who had
      congenital cataract extraction without IOL implantation. In patients in whom
      inadequate dilation precludes the detection of capsular support, posterior
      ciliary sulcus-supported secondary IOL implantation should be considered
      preoperatively. Although the technique enhances surgical planning and informed
      patient consent, the final decision occurs at the time of surgery with direct
      visualization of the ciliary sulcus support.

PMID- 16105607
TI  - Thin flap laser in situ keratomileusis: analysis of contrast sensitivity, visual,
      and refractive outcomes.
AB  - PURPOSE: To analyze refractive, visual, and contrast sensitivity outcomes of
      laser in situ keratomileusis (LASIK) performed under thin flaps (less than 100
      microm), and compare them with those of conventional thicker flaps. SETTING:
      Clinica Baviera, Instituto Oftalmologico Europeo, Madrid, Spain. METHODS: This
      retrospective study comprised 280 consecutive eyes that had LASIK for myopia
      using the Moria LSK-One microkeratome and the Technolas 217C excimer laser.
      Efficacy, predictability, and contrast sensitivity indicators were compared
      between 3 groups of flap thickness: thin (<100 microm, n = 105), medium (100 to
      129 microm, n = 122), and thick (>130 microm, n = 53). RESULTS: Refractive
      results were excellent and comparable between the 3 groups; however, visual
      outcomes-measured as efficacy, postoperative evolution of uncorrected visual
      acuity, and contrast sensitivity-test were significantly better in the thin flap
      group. Efficacy results were 92.9%, 91.0%, and 81.0% in the thin, medium, and
      thick flap groups, respectively (P < .05), and the rate of enhancements was 0%,
      2.3%, and 5.6%, respectively. With regard to contrast sensitivity, changes
      between preoperative and postoperative values at month 3 of follow-up, the thin
      flap group achieved the preoperative levels at 3 spatial frequencies (3, 6, and
      18 cycles per degree), while the thicker flap groups maintained lower than
      preoperative levels at more than 2 spatial frequencies. When comparing contrast
      sensitivity values between the 3 groups, the thin flap group also obtained the
      best results at lower spatial frequencies. CONCLUSIONS: Thin flap LASIK is a safe
      technique to correct myopic defects since it blends the advantages of surface and
      lamellar procedures (minimal debilitation of corneal biomechanical architecture
      with the rapid and comfortable visual recovery of lamellar approaches). Moreover,
      it achieves excellent refractive outcomes, a lower rate of enhancements, and a
      good visual performance with better contrast sensitivity test results.

PMID- 16105608
TI  - Clinical outcome of wavefront-guided laser in situ keratomileusis in eyes with
      moderate to high myopia with thin corneas.
AB  - PURPOSE: To evaluate the clinical outcome of wavefront-guided laser in situ
      keratomileusis (LASIK) for the treatment of moderate to high myopia associated
      with a thin cornea. SETTING: Enaim Laser Medical Center, Tel Aviv, Israel.
      METHODS: This retrospective study included 98 eyes of 49 patients with moderate
      to high myopia (-5.20 to -10.35 diopters [D]) and thin corneas (456 to 498 mum)
      treated with wavefront-guided LASIK (Zyoptix, Bausch & Lomb) and followed for 36
      months. Preoperative wavefront analysis was performed with a Hartmann-Shack
      aberrometer, and treatment was performed with the Technolas 217 z excimer laser
      system (Bausch & Lomb). Final refraction data, uncorrected visual acuity (UCVA),
      best corrected visual acuity (BCVA), optic zone size, ablation depth, optical
      aberrations, and night glare complaints were evaluated. RESULTS: Mean patient age
      was 28 years +/- 7 (SD), and mean preoperative spherical equivalent refraction
      was -7.06 D (range -5.20 to -10.35 D). Final UCVA ranged between 6/6 and 6/30.
      The safety index of the technique was 1.03, and the efficacy index was 0.67.
      Undercorrection of more than 0.50 D was observed in 41.3% of the high-myopic eyes
      (-7.00 to -10.35 D, n = 58) compared with 10% in the moderately myopic eyes (
      5.00 to -6.75 D, n = 40). A significant reduction in spherical aberration (Z(4)0)
      was found 12 months postoperatively in all eyes. Night glare was documented in 4
      eyes (4%) in the high myopia group. There were no cases of corneal ectasia.
      CONCLUSION: Zyoptix was safe in eyes with moderate to high myopia with relatively
      thin corneas (<498 microm). For myopia between -7.00 D and -10.35 D, a small
      optical zone (4.3 to 5.6 mm) may be applied as night glare was relatively rare,
      but significant undercorrection should be expected.

PMID- 16105609
TI  - Brimonidine versus dapiprazole: Influence on pupil size at various illumination
      levels.
AB  - PURPOSE: To evaluate the influence of dapiprazole versus brimonidine on pupil
      size at various illumination levels. SETTING: Department of Ophthalmology,
      Johannes Gutenberg-University, Mainz, Germany. METHODS: In randomized prospective
      study, 19 healthy volunteers received 2 ophthalmic solutions, dapiprazole and
      brimonidine, 1 in each eye, for intraindividual comparison. Before and after
      application, pupil diameter was measured using an infrared binocular pupillometer
      at 3 illumination levels (0.03, 0.82, and 6.4 lux). RESULTS: Only slight pupil
      dilation was observed under scotopic conditions after application of both agents.
      After 20 minutes, the median reduction in pupil width was 1.4 mm for brimonidine
      and 0.9 mm for dapiprazole. These effects were statistically significant for both
      agents (both P < .001). The maximum effect was observed after 40 minutes and
      remained stable through the next measurement at 180 minutes. Under mesopic
      lighting conditions, only a slight effect (<1 mm) was seen. CONCLUSIONS: Pupil
      mydriasis at scotopic illumination levels was reduced by both drugs in a similar
      fashion. Because of the slightly stronger effect of brimonidine, application of
      this agent 20 minutes before activities in dimly lit areas or at night may be
      recommended for photic phenomena following refractive surgery.

PMID- 16105610
TI  - Corneal penetration of fluoroquinolones: aqueous humor concentrations after
      topical application of levofloxacin 0.5% and ofloxacin 0.3% eyedrops.
AB  - PURPOSE: To investigate the penetration of topically applied levofloxacin 0.5%
      and ofloxacin 0.3% eyedrops into the aqueous humor of patients having cataract
      surgery. SETTING: Hochkreuzklinik Eye Hospital, Bonn, Germany. METHODS: In this
      randomized, investigator-masked study, 69 patients received 4 drops of either
      levofloxacin 0.5% or ofloxacin 0.3% eyedrops within 1 hour (60 min, 45 min, 30
      min, and 15 min) of elective cataract surgery. Aqueous humor samples of at least
      50 muL were drawn from the anterior chamber at the beginning of the cataract
      operation. The concentrations of the fluoroquinolones in the anterior chambers
      were measured using high-performance liquid chromatography. To exclude a dilution
      effect of the anterior chamber (AC), they were related to the AC volumes
      (measured by 3-dimensional modeling of central Orbscan [Bausch & Lomb] slit-image
      photos) and AC depths (measured by ultrasound). RESULTS: The mean concentration
      of levofloxacin (1139.9 ng/mL +/- 717.1 [SD]) in the aqueous humor was
      significantly higher (P = .0008) than that of ofloxacin (621.7 +/- 368.7 ng/mL).
      The aqueous humor concentrations correlated negatively with the measured volumes
      and depths of the ACs. CONCLUSIONS: The new fluoroquinolone, levofloxacin, is
      more soluble in water enabling the use of higher drug concentrations (0.5%)
      compared with other currently available fluoroquinolone eyedrops (0.3%). The
      concentration AC with levofloxacin eyedrops was about 2-fold that reached with
      ofloxacin eyedrops. The concentration of the antibacterial isomer was
      approximately 3.5 to 4 times higher when levofloxacin was administered, assuming
      negligible stereoselective uptake.

PMID- 16105611
TI  - Long-term outcome of excimer laser phototherapeutic keratectomy for treatment of
      Salzmann's nodular degeneration.
AB  - PURPOSE: To describe the technique and evaluate the long-term success of excimer
      laser phototherapeutic keratectomy (PTK) for treatment of Salzmann's nodular
      degeneration. SETTING: Department of Ophthalmology, University of Erlangen
      Nurnberg, Erlangen, Germany. METHODS: This retrospective study comprised 22 eyes
      of 14 patients who consecutively had PTK for superficial corneal opacities in
      Salzmann's nodular degeneration between January 1990 and November 2003. In all
      cases, the nodules and as much pannus tissue as possible were removed with a
      hockey knife. Afterward, the laser ablation (MEL 60 or 70, Carl Zeiss-Meditec)
      was performed with repeated application of masking fluid to remove further scar
      tissue and smooth the surface. Intended depth of laser ablation ranged from 10 to
      100 microm (mean: 41 microm +/- 43 [SD]). RESULTS: In 86% of eyes, visual acuity
      improved after PTK, from 0.4 +/- 0.2 preoperatively to 0.7 +/- 0.3
      postoperatively. The mean myopic shift was 1.5 +/- 0.7 diopters [D]. Median
      refractive cylinder changed from 1.0 D preoperatively to 0.7 D postoperatively.
      The median surface regularity index/surface asymmetry index (SRI/SAI) of the TMS
      1 topography analysis system (Tomey) decreased from 2.0/1.6 preoperatively to
      1.2/1.2 postoperatively. In 4 (18%) of 22 eyes, a recurrence had to be treated by
      repeat PTK during a mean follow-up of 2.0 +/- 1.8 years. CONCLUSIONS: Results
      indicate that PTK is an effective and safe procedure for treatment of Salzmann's
      nodular degeneration. Laser ablation should be combined with prior mechanical
      removal of nodules and excessive pannus tissue.

PMID- 16105612
TI  - Peripheral sterile corneal infiltrates after refractive surgery.
AB  - PURPOSE: To report 5 eyes of peripheral sterile corneal infiltrates after
      refractive surgery. SETTING: Department of Ophthalmology, Soroka University
      Medical Center, Beer-Sheva, Israel, and Enaim Ophthalmological Center, Jerusalem,
      Israel. METHODS: Three patients had bilateral refractive procedures for
      correcting myopia. The procedures included laser epithelial keratectomy in 2
      eyes, laser in situ keratomileusis (LASIK) in 2 eyes using a keratome, and LASIK
      in 1 eye using femtosecond laser. RESULTS: All the patients complained of ocular
      pain between 1 and 3 days after the procedure. A ring stromal infiltrate
      peripheral to the flap edge with intact epithelium and an intervening clear zone
      between the peripheral corneal infiltrates and the limbus was observed in 5 eyes
      without anterior chamber reaction. All cases improved after several days of
      topical steroid and antibiotic treatment and systemic steroid. Final visual
      acuity was 20/25 or better in all cases. CONCLUSIONS: The exact mechanism of this
      complication is still unknown, which can be confused with infectious keratitis.
      It is important to maintain a high degree of suspicion for infectious keratitis
      because the management is very different. The potential outcome can be much worse
      if the keratitis is due to an infectious etiology which can appear after all
      types of refractive laser procedures.

PMID- 16105613
TI  - Fluoroquinolone therapy in Mycobacterium chelonae keratitis after lamellar
      keratectomy.
AB  - PURPOSE: To characterize a rabbit model of Mycobacterium chelonae keratitis after
      lamellar keratectomy and assess the effectiveness of fluoroquinolone therapy.
      SETTING: University Laboratory, University of California, Irvine, California,
      USA. METHODS: Twenty-eight New Zealand white rabbits had unilateral lamellar
      keratectomy with placement of 2.5 x 10(5) colony-forming units of log-phase M
      chelonae under each flap. Eyes (7 per group) were randomized and treated with
      sterile balanced salt solution, gatifloxacin 0.3%, ciprofloxacin 0.3%, or
      levofloxacin 0.5% 4 times daily. Two masked observers examined all eyes on days
      2, 5, and 7 and weekly for 4 weeks. Severity of disease and bacterial culture
      results were the main outcomes measured. The means and standard deviations were
      calculated, and differences between the groups were statistically analyzed.
      RESULTS: All eyes developed clinical disease. At the time the rabbits were
      killed, eyes treated with balanced salt solution, ciprofloxacin, levofloxacin,
      and gatifloxacin were culture positive in 6 (85.7%), 7 (100%), 6 (85.7%), and 3
      (42.9%) of 7 eyes per group, respectively. Frequency of positive culture and the
      severity of clinical disease in gatifloxacin-treated eyes were significantly less
      (P < .05) than in the other groups combined. CONCLUSIONS: The rabbit model of M
      chelonae keratitis was successfully developed in our study. A fourth-generation
      quinolone (gatifloxacin) showed the best performance among the fluoroquinolones
      tested in our experimental approach. The fourth-generation fluoroquinolone,
      gatifloxacin, could be effectively used for the treatment of mycobacterial
      keratitis.

PMID- 16105614
TI  - Absence of scar formation in human donor cornea with prior laser in situ
      keratomileusis.
AB  - PURPOSE: To investigate transglutaminases (enzymes capable of cross-linking
      extracellular matrix proteins to proteolysis-resistant complexes during scar
      tissue formation) in a human donor cornea after successful laser in situ
      keratomileusis (LASIK) without clinical complications and to compare with the
      results in a human donor cornea with corneal scarring after corneal injury.
      SETTING: Department of Ophthalmology, Ludwig-Maximilians University, Munich,
      Germany. METHODS: A donor cornea with prior uneventful LASIK treatment and 1 with
      corneal scarring after penetrating injury were investigated. Cryostat sections
      were stained immunohistochemically for tissue transglutaminase (tTG), keratocyte
      transglutaminase (kTG), and their reaction product epsilon-(gamma-glutamyl)
      lysine. RESULTS: With light microscopy, the flap interface of the LASIK-treated
      eye could hardly be detected, while in the injured eye, infiltration of cells and
      a clear margin next to the scar formation were present. Immunohistochemistry
      demonstrated a distinct staining for tTG, kTG, and epsilon-(gamma-glutamyl)
      lysine in the corneal scar. In contrast, neither transglutaminase nor epsilon
      (gamma-glutamyl)-lysine staining could be observed at the flap margin or in the
      interface of the LASIK-treated donor eye. CONCLUSIONS: Irreversible protein cross
      linking of transglutaminases via epsilon-(gamma-glutamyl)-lysine connections seem
      to be indicators for scarring in corneal wound healing. The absence of
      transglutaminases and their reaction product epsilon-(gamma-glutamyl)-lysine in a
      LASIK-treated cornea supports the idea of missing scar tissue formation after
      LASIK surgery.

PMID- 16105615
TI  - Observation of the corneal flap interface with metal particles in a rabbit model.
AB  - PURPOSE: To observe changes, such as diffuse lamellar keratitis, at the corneal
      interface when metal particles from microkeratome blades were left in rabbit
      eyes. SETTING: Department of Ophthalmology, Tokyo Dental College, Suidobashi
      Hospital, Tokyo, Japan. METHODS: Following the creation of a corneal flap with
      microkeratome, metal particles from a microkeratome blade were placed at the
      corneal interface in 14 rabbit eyes. Microscopic and histopathologic changes were
      compared with those in the control eyes (n = 4), which did not receive any metal
      particles. Each examination was conducted at 3 days, 2 weeks, and 1 and 3 months
      postoperatively. The change in the depth of the metal particles was also
      measured. RESULTS: Slitlamp examination did not show an inflammatory reaction or
      corneal opacification in any eye (100%) with metal particles at the flap
      interfaces. Histopathologic examinations showed no obvious changes at the flap
      interfaces or around the metal particles in any eye. CONCLUSION: Inflammatory
      reactions, such as diffuse lamellar keratitis, do not appear to be induced by
      metal particles from the microkeratome blade itself.

PMID- 16105616
TI  - Evaluation of the cataractogenic effect of viscoanesthetic solutions on the
      rabbit crystalline lens.
AB  - PURPOSE: To evaluate the toxicity and cataractogenic effect of solutions
      combining sodium (Na) hyaluronate 1.0% and 1.5% with lidocaine 1.0% on the rabbit
      crystalline lens. The amount of pupil dilation provided by the addition of
      lidocaine to the Na hyaluronate solutions was also assessed. SETTING: John A.
      Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. METHODS: Five
      solutions were injected into the anterior chamber of 18 pigmented rabbits in a
      randomized manner by the same surgeon, the intraocular component of VisThesia (Na
      hyaluronate 1.5%/lidocaine 1.0%), the intraocular component of VisThesia Light
      (Na hyaluronate 1.0%/lidocaine 1.0%), Ophthalin Plus (Na hyaluronate 1.5%), and a
      balanced salt solution; and both eyes of 2 other rabbits were injected with
      nonpreserved aqueous lidocaine 1.0%. The pupil diameter of each eye was measured
      before injection, immediately after, and 1 and 5 minutes after injection. After a
      follow-up of 3 months with slitlamp examinations, the rabbits were killed, and
      their eyes were enucleated. The crystalline lenses were evaluated from a
      posterior or Miyake-Apple view, and the eyes were fixated in 10% formalin for
      histopathologic analyses. RESULTS: Pupil diameter was significantly larger 1 and
      5 minutes after injection in the VisThesia (P = .01 and P = .007) and VisThesia
      Light (P = .008 and P = .007) groups, whereas the differences were not
      significant in the Ophthalin Plus (P = .317 and P = .102) and balanced salt
      solution groups (P = .317 and P = .180). Fast and large pupillary dilation was
      observed in the aqueous lidocaine group, starting during the injection. No
      differences in the transparency of the natural lens and the red fundus reflex
      were noted during slitlamp examinations. Postmortem analyses from a posterior
      view also showed no differences in the transparency of the crystalline lens. The
      histopathologic appearance of the lens capsule, anterior and equatorial lens
      epithelial cells, and epithelial lens bow was comparable in the eyes, without
      signs of cell vacuolization or disruption. CONCLUSIONS: Intracameral injection of
      the solutions used in this study caused no localized opacity or overall change in
      the transparency of the crystalline lenses as observed during clinical and
      postmortem examinations as well as histopathologic analyses of the enucleated
      rabbit eyes. Viscoanesthesia may have application in phakic intraocular lens
      implantation.

PMID- 16105617
TI  - Acute haptic-induced ciliary sulcus irritation associated with single-piece
      AcrySof intraocular lenses.
AB  - We report an analysis of 3 single-piece hydrophobic acrylic intraocular lenses
      (IOLs) that were explanted because of complications related to the presence of
      their haptics in the ciliary sulcus. In 2 cases, the IOL was primarily implanted
      in the ciliary sulcus because of inadequate posterior capsule support. In the
      third case, postoperative displacement of 1 haptic in the sulcus was associated
      with hyphema and vitreous hemorrhage. Ultrasound biomicroscopy confirmed the
      contact between the haptic and iris. Areas of iris atrophy were observed in all
      cases. Light microscopy and scanning electron microscopy of the explanted lenses
      revealed the presence of pigmentary dispersion on the anterior surfaces. In Case
      3, the pigments were concentrated on the surface of the haptic that was displaced
      from the capsular bag and on the corresponding optic-haptic junction. Scanning
      electron microscopy also showed the IOL's squared edges and unpolished side
      walls. The flexibility and thickness of the single-piece hydrophobic acrylic
      haptics, as well as the square optic and haptic edges, may increase the risk for
      iris chafing when the haptics are in the sulcus. Therefore, sulcus fixation of
      this IOL design is not recommended.

PMID- 16105618
TI  - Phacoemulsification, persistent hypotony, and cyclodialysis clefts.
AB  - A retrospective noncomparative case-note analysis of 3 men presenting with
      persistent hypotony after routine phacoemulsification cataract surgery was
      performed. All patients had a previous history of significant blunt ocular
      trauma. All patients had surgical repair of the cyclodialysis clefts, 1 with
      cleft cryopexy and 2 with formal cleft closure with a limbal-based double scleral
      flap technique. All patients achieved closure of the cyclodialysis clefts
      following surgical intervention with complete resolution of hypotony. Mean
      preoperative intraocular pressures improved from 3, 4 and 3 mm Hg in the 3 cases
      to 11, 16, and 17 mm Hg postoperatively. Visual acuities improved from
      preoperative readings of counting fingers, 6/36 and 6/24 in the 3 cases to 6/6,
      6/9, and 6/9 postoperatively. Persistent hypotony because of possible activation
      of a preexisting doormant cyclodialysis cleft following routine atraumatic
      phacoemulsification cataract surgery in previously traumatized eyes has not been
      reported.

PMID- 16105619
TI  - Anterior megalophthalmos in a family with 3 female siblings.
AB  - This report describes different modes of management in 3 sisters with anterior
      megalophthalmos. We report our management of the anterior megalophthalmos and a
      new technique of anterior chamber intraocular lens implantation, which was used
      in 1 case.

PMID- 16105620
TI  - Cyclooxygenase-2 inhibitors: a new therapeutic option in the treatment of macular
      edema after cataract surgery.
AB  - Two patients had uneventful phacoemulsification. After initial improvement,
      vision deteriorated because of cystoid macular edema (CME). In 1 patient,
      treatment with systemic nonsteroidal antiinflammatory drugs showed significant
      improvement in visual acuity but had to be discontinued because of side effects
      and a relapse of the disease. In the other patient, this therapy was not
      sufficient. Both patients were given valdecoxib, a cyclooxygenase-2 inhibitor.
      The new therapy was tolerated well and led to significant and stable improvement
      in visual acuity in both patients. To our knowledge, this is the first report of
      using a cyclooxygenase-2 inhibitor in the treatment of clinically significant
      CME.

PMID- 16105621
TI  - Late spontaneous dislocation (disenclavation) of iris-claw intraocular lenses.
AB  - We report 2 cases of late spontaneous dislocation (disenclavation) of an iris
      claw intraocular lens (IOL) after cataract surgery. Case 1 was a 65-year-old
      woman who presented with diminution of vision in the left eye. She had left eye
      cataract surgery 17 years ago with iris-claw IOL implantation. In the left eye,
      there was temporal disenclavation of IOL and the free end was touching the
      endothelium at 4 o'clock position. Case 2 was a 32-year-old man who first
      presented in 1994. He was a high myope and had cataract extraction in both eyes
      with iris-claw IOL implantation 7 years ago. He presented in October 2003 with
      complaint of blurred vision in the left eye of 4 months' duration. In the left
      eye, the IOL had disenclavated temporally and was hanging inferiorly. Case 1 had
      IOL exchange. In Case 2, IOL exchange was advised.

PMID- 16105622
TI  - Intermittent myopic shift of 4.0 diopters after implantation of an Artisan iris
      supported phakic intraocular lens.
AB  - A 45-year-old man with bilateral high myopia and myopic astigmatism had
      uneventful implantation of a -10.5 diopters (D) Artisan iris-fixated anterior
      chamber phakic intraocular lens (PIOL) (Ophtec) in both eyes. In the first days
      after surgery, uncorrected visual acuity (UCVA) was 20/16 in the right eye and
      20/16 in the left; the position of the PIOL was stable. Ten days after surgery,
      the left eye developed a myopic shift of 4.0 D. Further examination showed that
      the myopia disappeared when the pupil was medically dilated. After the pupil
      returned to a natural position, the myopic shift reappeared. Because there were
      no changes in the subsequent 4 months, we decided to exclavate the IOL, rotate it
      by 10 degrees, and reenclavate it with less tissue. The myopic shift did not
      return over the following 20 months, and the UCVA was 20/20. In rare cases, iris
      fixated anterior chamber IOLs may induce refractive changes related to effects on
      the surrounding anatomic structures. This may be corrected by phakic IOL rotation
      or reenclavation of the phakic IOL with less tissue.

PMID- 16105623
TI  - Mycobacterium chelonae-Mycobacterium abscessus complex clear corneal wound
      infection with recurrent hypopyon and perforation after phacoemulsification and
      intraocular lens implantation.
AB  - We report a clear corneal wound infection occurring in a 74-year-old man caused
      by a member of the Mycobacterium chelonae-Mycobacterium abscessus complex,
      presenting as crystalline keratopathy with recurrent hypopyon. This led to
      perforation after phacoemulsification with posterior chamber intraocular lens
      implantation. Only after corneal biopsy of the incision was the causative
      organism isolated and found to be sensitive to clarithromycin and ciprofloxacin.
      Despite aggressive therapy, a full-thickness corneal perforation developed,
      requiring emergent cyanoacrylate glue to preserve ocular integrity. Both the
      difficulty and delays in obtaining a correct diagnosis led to severe ocular
      morbidity. Infectious lamellar keratitis limited to the clear cornea
      phacoemulsification incision is rare, but some unusual organisms such as atypical
      mycobacteria may be encountered.

PMID- 16105624
TI  - Pupil block glaucoma after neodymium:YAG capsulotomy in a patient with a
      partially subluxated posterior chamber intraocular lens.
AB  - A 73-year-old-woman presented following neodymium:YAG capsulotomy for posterior
      capsular opacification with acute glaucoma. Previous cataract surgery had left
      her with a subluxated lens. Cornea edema obscured detail of the anterior chamber,
      but the edge of the lens could be seen clearly within the pupillary space. This
      produced a diagnostic dilemma because no obvious cause for pupil block could be
      seen. She failed to respond to medical therapy and had a laser iridotomy,
      following which her symptoms resolved. We believe this case demonstrates the
      importance of a laser iridotomy to exclude pupil block glaucoma when adequate
      visualization of the pupillary space is obscured.

PMID- 16105625
TI  - Indocyanine green-emitted fluorescence as an aid to anterior capsule
      visualization.

PMID- 16105626
TI  - Endoscope-aided cataract surgery in corneal opacity associated with aniridia.

PMID- 16105627
TI  - Implantation of foldable intraocular lens with anterior optic capture in isolated
      posterior capsule rupture.

PMID- 16105628
TI  - Scleral and conjunctival melt caused by a sponge used for topical anesthesia.

PMID- 16105630
TI  - Differences in education, knowledge, self-management activities, and health
      outcomes for patients with heart failure cared for under the chronic disease
      model: the improving chronic illness care evaluation.
AB  - BACKGROUND: The objective of this study was to determine whether participation in
      a quality improvement (QI) collaborative for heart failure (HF) was associated
      with better interpersonal aspects of care and health outcomes. METHODS AND
      RESULTS: We conducted a cross-sectional telephone survey of patients in 6
      organizations who participated in a QI collaborative for HF (participants, n =
      387) and 6 comparable control organizations (controls, n = 414) and measured
      provider-patient communication, education received, knowledge of HF, self
      management behaviors, satisfaction, and quality of life. The participant group
      patients were more likely to report their doctor and nurse discussed treatment
      options and reviewed self-management (P < .01 for both). A total of 88% of
      participants were told to weigh themselves daily and record their weight compared
      with 34% of controls (P < .01). Participants were more likely to know how often
      to check their weight (P < .01), recognize symptoms of worsening HF (P < or = .01
      for all), have a scale (P = .002), and monitor their weight daily (P < .001).
      Participants had similar quality of life but fewer emergency department visits
      and hospitalizations. CONCLUSION: Participation in a QI collaborative for HF was
      associated with better communication, education, and knowledge, and lower health
      care use. Collaboratives may be a useful method for disseminating quality
      improvement strategies.

PMID- 16105631
TI  - The relationship between B-type natriuretic peptide and health status in patients
      with heart failure.
AB  - BACKGROUND: Although B-type natriuretic peptide (BNP) levels have been proposed
      as a means of assessing disease severity in patients with heart failure, it is
      not known if BNP levels are correlated with health status (symptom burden,
      functional limitation, and quality of life). METHODS AND RESULTS: We studied 342
      outpatients with systolic heart failure from 14 centers at baseline and 6 +/- 2
      weeks with BNP levels and the Kansas City Cardiomyopathy Questionnaire (KCCQ), a
      heart-failure-specific health status instrument. We assessed the correlation
      between KCCQ scores and BNP at baseline and changes in KCCQ according to changes
      in BNP levels between baseline and follow-up. Mean baseline BNP levels were 379
      +/- 387 pg/mL and mean KCCQ summary scores were 62 +/- 23 points. Although
      baseline BNP and KCCQ were both associated with New York Heart Association
      classification (P < .001 for both), BNP and KCCQ were not correlated (r(2) =
      0.008, P = .15). There was no significant relationship between changes in BNP and
      KCCQ regardless of the threshold used to define a clinically meaningful BNP
      change. For example, using >50% BNP change threshold, KCCQ improved by 3.7 +/-
      14.2 in patients with decreasing BNP, improved by 1.7 +/- 13.6 in patients with
      no BNP change, and improved by 1.0 +/- 13.4 in patients with increasing BNP (P =
      .6). CONCLUSION: BNP and health status are not correlated in outpatients with
      heart failure in the short term. This suggests that these measures may assess
      different aspects of heart failure severity, and that physiologic measures do not
      reflect patients' perceptions of the impact of heart failure on their health
      status.

PMID- 16105632
TI  - The difficult task of evaluating how to monitor patients with heart failure.

PMID- 16105633
TI  - Effects of intravenous nesiritide on pulmonary vascular hemodynamics in pulmonary
      hypertension.
AB  - BACKGROUND: Nesiritide is effective in the treatment of decompensated heart
      failure (HF). We evaluated the acute hemodynamic effects of nesiritide, a
      recombinant B-type natriuretic peptide, in patients with HF and pulmonary
      hypertension (PH). METHODS AND RESULTS: Twenty patients with HF and PH (mean
      pulmonary arterial [PA] pressure >25 mm Hg) were enrolled: 10 with postpulmonary
      capillary wedge (PCW) >15 mm Hg and 10 with precapillary PH (PCW) < or =15. The
      pulmonary and systemic hemodynamics were determined by right heart
      catheterization at baseline and at 15 and 30 minutes after an intravenous
      nesiritide infusion (2 mcg/kg bolus and 0.01 mcg.kg.min). For the patients with
      postcapillary PH, the mean left ventricular ejection fraction was 28 +/- 15%.
      After the 30-minute nesiritide infusion, right atrial (RA) pressure decreased 48%
      (P < .0001), mean PA pressure decreased 29% (P < .0001), PCW pressure decreased
      40% (P < .0001), cardiac index (CI) increased 35% (P = .009), pulmonary vascular
      resistance index (PVRI) decreased 35% (P = .01), and arteriovenous oxygen
      difference (AVDO(2)) decreased 27% (P = .0003). For precapillary PH patients,
      there was no change in RA, PA, or PCW pressure, nor any change in CI, PVRI, or
      AVDO(2). CONCLUSIONS: Nesiritide acutely and significantly reduced PA pressure,
      PVRI, and biventricular filling pressures in patients with postcapillary PH.
      However, for patients with precapillary PH, nesiritide had no significant acute
      hemodynamic effect on the pulmonary hemodynamics. The lack of acute beneficial
      effects of nesiritide in patients with advanced precapillary PH may be related to
      their relatively fixed remodeling of the pulmonary vasculature.

PMID- 16105634
TI  - Safety and efficacy of repeated sauna bathing in patients with chronic systolic
      heart failure: a preliminary report.
AB  - BACKGROUND: We sought to determine the safety and efficacy of repeated 60 degrees
      C sauna bathing in patients with chronic systolic congestive heart failure (CHF).
      METHODS AND RESULTS: This study included 15 hospitalized CHF patients (New York
      Heart Association class = 2.8 +/- 0.4) in stable clinical condition on
      conventional treatments. Sauna bathing was performed once per day for 4 weeks.
      Repeated sauna bathing was safely completed without any adverse effects in all
      patients. Symptoms improved in 13 of 15 patients after 4 weeks. Sauna bathing
      decreased systolic blood pressure without affecting heart rate, resulting in
      significant decrease in the rate-pressure product (6811 +/- 1323 to 6292 +/-
      1093). Echocardiographic left ventricular ejection fraction was significantly
      increased from 30 +/- 11 to 34 +/- 11%. Sauna bathing significantly improved
      exercise tolerance manifested by prolonged 6-minute walking distance (388 +/- 110
      to 448 +/- 118 m), increased peak respiratory oxygen uptake (13.3 +/- 1.8 to 16.3
      +/- 2.1 mL/kg/min), and enhanced anaerobic threshold (9.4 +/- 1.2 to 11.5 +/- 1.9
      mL/kg/min). Four-week bathing significantly reduced plasma epinephrine (40 +/- 42
      to 21 +/- 23 pg/mL) and norepinephrine (633 +/- 285 to 443 +/- 292 pg/mL). Sauna
      bathing reduced the number of hospital admission for CHF (2.5 +/- 1.3 to 0.6 +/-
      0.8 per year). CONCLUSION: Repeated 60 degrees C sauna bathing was safe and
      improved symptoms and exercise tolerance in chronic CHF patients. Sauna bathing
      may be an effective adjunctive therapy for chronic systolic CHF.

PMID- 16105635
TI  - Functional abnormalities in brain areas that mediate autonomic nervous system
      control in advanced heart failure.
AB  - BACKGROUND: Heart failure patients show substantial gray matter loss in brain
      areas that mediate autonomic control. Those injuries may lead to the aberrant
      autonomic patterns found in the syndrome. The purpose of this study was to
      determine if functional responses in the brain to an autonomic challenge would
      differ from normal patterns and would appear in areas of previously-demonstrated
      gray matter loss. METHODS AND RESULTS: We subjected 6 heart failure patients
      (left ventricular ejection fraction 0.15 +/- 0.08; age 49 +/- 12 years) and 16
      controls (age 48 +/- 11 years) to a forehead cold pressor challenge that would
      enhance sympathetic outflow and assessed functional magnetic resonance image
      signals over the entire brain during a 54-second baseline and 90-second
      challenge. Application of the cold stimulus elicited aberrant responses in the
      anterior and posterior hypothalamus, bilateral amygdala, hippocampus, cerebellar
      cortex, insular cortex, mid/posterior cingulate cortex, right ventral frontal
      cortex, and temporal and frontal cortices. Many of the areas neighbored or
      overlaid regions of previously demonstrated gray matter damage. Both classical
      autonomic control regions, as well as brain areas modulating these sites showed
      deficient responses, some of which appeared to be of an overdampened or
      underdampened nature. CONCLUSION: The findings suggest that the earlier
      demonstrated changes in brain structure in heart failure result in aberrant
      functional neural responses; these dysfunctions may contribute to progression of
      the pathology in heart failure.

PMID- 16105636
TI  - Serial measurements of peripheral vascular reactivity and exercise capacity in
      congestive heart failure and after heart transplantation.
AB  - BACKGROUND: The regulation of nutritive blood flow to skeletal muscles during
      exercise seems to make an important contribution to exercise capacity. In
      congestive heart failure (CHF) this regulation seems to be impaired, with
      attenuated peripheral vasodilatory capacity. The results regarding improvement of
      peripheral vasoreactivity after heart transplantation (HTx) are conflicting, and
      the contribution of impaired peripheral vasoreactivity to the observed reduced
      exercise capacity among heart transplant recipients (HTR) has not been well
      elucidated. We therefore assessed the reversibility of impaired vasoreactivity in
      forearm and calf after HTx with relationship to exercise capacity. METHODS AND
      RESULTS: The vasoreactivity of both forearm and calf was studied with venous
      occlusion plethysmography and related to exercise capacity in 64 patients with
      CHF and in 22 controls. Of these patients, 29 patients underwent HTx, and the
      same measurements were performed 10 days, 6 months and 1 year after HTx, and in a
      group of 15 HTR who had undergone HTx several years ago. Our main findings were
      (1) impaired resting blood flow in patients with CHF improved after HTx and even
      surpassed levels of controls; (2) peak forearm blood flow remained attenuated
      early after HTx, but normalized during the first year postoperatively; (3) both
      forearm and calf minimal resistance remained elevated after HTx; (4) vascular
      reactivity displays regional variations in forearm and calf both during CHF and
      after HTx; and (5) peripheral vascular reactivity relate to exercise performance
      in both patients with CHF and HTR, but the relationship seemed more pronounced in
      CHF. CONCLUSION: With impaired vasoreactivity related to limited exercise
      capacity in CHF, improvement is evident after HTx, but both forearm and calf
      minimal resistance remains elevated. These findings suggest increased
      vasoconstrictor drive to both exercising and non-exercising muscles, possibly
      contributing to persistent physical limitation after HTx.

PMID- 16105637
TI  - Depression and anxiety in heart failure.
AB  - BACKGROUND: Although common among patients with heart failure, depression and
      anxiety have been relatively neglected by researchers and practitioners. Both
      depression and anxiety have been implicated in contributing independently to the
      poor outcomes seen in patients with heart failure. Emphasis in the literature is
      on physical symptom recognition and management, in contrast to the patient's
      perspective of the effects of heart failure on his or her daily life. METHODS AND
      RESULTS: This review summarizes and integrates research findings on anxiety and
      depression and translates these findings to clinical practice. Depression and
      anxiety are prevalent among patients with heart failure and require assessment
      and intervention. Short-term nonpharmacologic approaches, in conjunction with
      drug therapy, hold promise for successful management of patients who are
      depressed or anxious. CONCLUSION: Carefully designed clinical trials that are
      tailored to individual needs, yet are embedded within a systemic framework, are
      needed to inform clinicians regarding optimal practices for the treatment of
      patients with heart failure who suffer from depression or anxiety.

PMID- 16105638
TI  - Arrhythmias after orthotopic heart transplantation.
AB  - BACKGROUND: Arrhythmias frequently occur after orthotopic heart transplantation
      (OHT). METHODS AND RESULTS: The most common are ventricular premature complexes,
      atrial premature complexes, sinus or junctional bradycardia, atrial fibrillation,
      and atrial flutter, all of which have varying clinical significance depending on
      associated or causative conditions. Unique etiologic factors such as allograft
      rejection, transplant coronary artery disease, and altered anatomy and autonomic
      nervous system changes require that arrhythmias be treated differently after OHT
      compared with the general population. CONCLUSION: The potentially severe
      ramifications of allograft rejection and coronary artery disease make treatment
      of these disorders in the setting of arrhythmias as important as treating the
      arrhythmias themselves. At the same time, autonomic denervation and altered
      anatomy after transplantation complicate drug and device therapies.

PMID- 16105639
TI  - Increased reactive oxygen species production and functional alterations in
      antioxidant enzymes in human failing myocardium.
AB  - BACKGROUND: The nature of oxidative stress and the activity of antioxidant enzyme
      systems are incompletely characterized in the failing human heart. METHODS AND
      RESULTS: We obtained ventricular myocardium from failing, explanted human hearts
      in patients with nonischemic dilated cardiomyopathy at the time of heart
      transplant to examine whether reactive oxygen species (ROS) production and
      antioxidant enzyme activity or expression were altered in end-stage human heart
      failure. Nonfailing myocardium was obtained from organ donors who were not
      eligible for transplantation. Electroparamagnetic resonance (EPR) with the O(2)(
      ) spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide demonstrated that
      formation of superoxide anion was increased more than 2-fold in the failing (P <
      .001 vs. nonfailing) myocardium. Manganese superoxide dismutase (MnSOD) mRNA and
      catalase mRNA expression were increased by 52% (P=.05) and 116% (P < .05),
      respectively, in failing vs. nonfailing hearts. Copper-zinc superoxide dismutase
      (CuZnSOD) mRNA and glutathione peroxidase-1 (GPx-1) mRNA were unchanged. The
      expression of MnSOD, CuZnSOD, and catalase mRNA showed moderate correlation,
      suggesting coordinate regulation of gene expression. Activity was no different
      with regard to catalase, GPx-1, and glucose-6-phosphate dehydrogenase. MnSOD
      activity accounted for approximately 90% of total SOD activity, and was markedly
      decreased in failing hearts (by 61%, P < .05). MnSOD protein expression by
      western blot analysis was decreased in the failing group (P < .05 vs.
      nonfailing). CONCLUSION: The decrease in MnSOD activity in failing myocardium, in
      the setting of increased mRNA expression, may reflect decreased translation or
      processing, or a posttranslational modification of MnSOD. The increase in MnSOD
      mRNA in failing hearts is consistent with the thesis that there is increased
      oxidative stress in failing myocardium that leads to increase transcription of
      antioxidant enzymes. The source of this direct measure of ROS is likely
      superoxide. These observations have implications for the pathophysiology and
      treatment of heart failure.

PMID- 16105640
TI  - A successful rapid desensitization protocol in a loop diuretic allergic patient.

PMID- 16105641
TI  - What is the in vivo mechanism of action of levosimendan?

PMID- 16105643
TI  - Evaluation of three growth factors in combinations of two for temporomandibular
      joint disc tissue engineering.
AB  - Tissue engineering of the temporomandibular joint disc could be a great value in
      treatments that require discectomy. Potential benefit has been found in the use
      of three growth factors: insulin-like growth factor-I, basic fibroblast growth
      factor and transforming growth factor-beta1 in maintaining disc-like tissue in
      culture. In the present study, these three growth factors were combined in pairs
      and tested at two different concentrations over a 6-week period. All combinations
      of the growth factors appear to be beneficial since only three-quarters of the
      control constructs (without growth factors) retained mechanical integrity,
      compared with the majority of constructs exposed to growth factors. Importantly,
      the concentrations of the presented growth factors had a significant impact on
      the cellularity of constructs at Week 6. When a high concentration of the two
      growth factors was used, at least twice as many cells remained in the constructs
      compared with controls.

PMID- 16105644
TI  - Tissue-specific expression of Fgfr2b and Fgfr2c isoforms, Fgf10 and Fgf9 in the
      developing chick mandible.
AB  - Experimental evidence has demonstrated the importance of FGF signalling in
      morphogenesis of the mandibular processes. FGFs transmit their signals through
      four tyrosine kinase transmembrane receptors (FGFRs). Alternative splicing in
      FGFRs including FGFR2 generates different isoforms that exhibit different ligand
      specificities, exclusive tissue distributions and specific biological functions.
      Despite extensive information regarding the isoform-specific patterns of
      expression Fgfr2c and Fgfr2b during morphogenesis of many organs, a comparative
      analysis of these specific isoforms in the chick mandible has not been reported.
      To better understand the function of FGFR2 in mandibular morphogenesis, we have
      analysed the expression Fgfr2b, Fgfr2c and their putative ligands Fgf10 and Fgf9,
      in the developing chick mandibular processes by in situ hybridisation and RT-PCR.
      Our observations show that Fgfr2b was primarily expressed in the mandibular
      epithelium while Fgfr2c was expressed in the mandibular mesenchyme including
      Meckel's cartilage. Fgf9 and Fgf10 were expressed in a variety of craniofacial
      regions including the mandibular epithelium and mesenchyme respectively. The
      temporal and spatial distributions of Fgfr2b, Fgfr2c, Fgf10 and Fgf9 in the
      developing mandible reported in this study make them attractive candidates for
      involvement in epithelial-mesenchymal signalling interactions that are known to
      be necessary for proper mandibular outgrowth and morphogenesis.

PMID- 16105645
TI  - Analysis of polymorphic sites in the promoter of the nitric oxide synthase 2
      gene.
AB  - A point mutation (G --> C) in the gene promoter for the human nitric oxide
      synthase (NOS) 2 at position -954 is associated with protection against severe
      Plasmodium falciparum malaria in Gabon. Carriers of this mutation show higher
      basal levels of nitric oxide production than wild type individuals. To obtain
      information about the possible binding transcription factors, nucleic proteins
      from the lung carcinoma cell line were enriched by affinity chromatography using
      DEAE-Sepharose and immobilized oligonucleotides derived from the promoter
      sequence. A mutational analysis was performed on 30 samples to detect
      polymorphisms in the NOS2 promoter region that contains important NF-kappaB
      sites. Three point mutations were identified in this region. In vitro studies
      with promoter constructs showed an altered expression of the marker gene
      depending on the promoter variant used.

PMID- 16105646
TI  - Butyrate-induced proapoptotic and antiangiogenic pathways in EAT cells require
      activation of CAD and downregulation of VEGF.
AB  - Butyrate, a short-chain fatty acid produced in the colon, induces cell cycle
      arrest, differentiation, and apoptosis in transformed cell lines. In this report,
      we study the effects of butyrate (BuA) on the growth of Ehrlich ascites tumor
      (EAT) cells in vivo. BuA, when injected intraperitoneally (i.p) into mice,
      inhibited proliferation of EAT cells. Further, induction of apoptosis in EAT
      cells was monitored by nuclear condensation, annexin-V staining, DNA
      fragmentation, and translocation of caspase-activated DNase into nucleus upon BuA
      treatment. Ac-DEVD-CHO, a caspase-3 inhibitor, completely inhibited BuA-induced
      apoptosis, indicating that activation of caspase-3 mediates the apoptotic pathway
      in EAT cells. The proapoptotic effect of BuA also reflects on the antiangiogenic
      pathway in EAT cells. The antiangiogenic effect of BuA in vivo was demonstrated
      by the downregulation of the secretion of VEGF in EAT cells. CD31
      immunohistochemical staining of peritoneum sections clearly indicated a potential
      angioinhibitory effect of BuA in EAT cells. These results suggest that BuA,
      besides regulating other fundamental cellular processes, is able to modulate the
      expression/secretion of the key angiogenic growth factor VEGF in EAT cells.

PMID- 16105647
TI  - Selective uptake and efflux of cholesteryl linoleate in LDL by macrophages
      expressing 12/15-lipoxygenase.
AB  - Oxidation of low density lipoprotein (LDL) is a critical step for atherogenesis,
      and the role of the 12/15-lipoxygenase (12/15-LOX) as well as LDL receptor
      related protein (LRP) expressed in macrophages in this process has been
      suggested. The oxygenation of cholesteryl linoleate in LDL by mouse macrophage
      like J774A.1 cells overexpressing 12/15-LOX was inhibited by an anti-LRP antibody
      but not by an anti-LDL receptor antibody. When the cells were incubated with LDL
      double-labeled by [3H]cholesteryl linoleate and [125I]apoB, association with the
      cells of [3H]cholesteryl linoleate expressed as LDL protein equivalent exceeded
      that of [125I]apoB, indicating selective uptake of [3H]cholesteryl linoleate from
      LDL to these cells. An anti-LRP antibody inhibited the selective uptake of
      [3H]cholesteryl ester by 62% and 81% with the 12/15-LOX-expressing cells and
      macrophages, respectively. Furthermore, addition of LDL to the culture medium of
      the [3H]cholesteryl linoleate-labeled 12/15-LOX-expressing cells increased the
      release of [3H]cholesteryl linoleate to the medium in LDL concentration- and time
      dependent manners. The transport of [3H]cholesteryl linoleate from the cells to
      LDL was also inhibited by an anti-LRP antibody by 75%. These results strongly
      suggest that LRP contributes to the LDL oxidation by 12/15-LOX in macrophages by
      selective uptake and efflux of cholesteryl ester in the LDL particle.

PMID- 16105648
TI  - Preparation, in vitro and in vivo evaluation of (99m)Tc-Annexin B1: a novel
      radioligand for apoptosis imaging.
AB  - To develop a radiopharmaceutical for apoptosis imaging, Annexin B1, a new Ca2+
      dependent phosphatidylserine (PS)-binding protein, was directly radiolabeled with
      (99m)Tc. This procedure yields up to 96% of radiochemical purity and higher
      radiolabeling efficiency. The preparation has been found to be sufficiently
      stable in vitro. Binding assay with human activated platelets indicated that
      (99m)Tc-Annexin B1 retained its PS binding activity. Biodistribution in mice
      revealed that (99m)Tc-Annexin B1 rapidly cleared from the blood and predominantly
      accumulated in the kidney. The increase in hepatic uptake in anti-Fas antibody
      treated mice correlated to histologic evidence of fulminant hepatic apoptosis.
      These data suggest that (99m)Tc-Annexin B1 can be used as a novel radiotracer to
      detect apoptosis in vivo.

PMID- 16105649
TI  - An intronic enhancer regulates cyclooxygenase-1 gene expression.
AB  - To identify cis-elements regulating PMA-induced prostaglandin H synthase-1 (PGHS
      1) gene expression in the human megakaryoblast cell line, MEG-01, we performed
      promoter reporter assays with a luciferase reporter vector containing the -2030/
      22 region of the human PGHS-1 gene. PMA treatment for 24 h increased PGHS-1
      promoter activity by twofold. Mutagenesis studies of the promoter revealed a
      single Sp1 site essential for PMA-inducible transcription. Insertion of a highly
      conserved 100 bp sequence cloned from intron 8 into the -2030/-22 reporter
      plasmid enhanced PMA-dependent transcription 10-fold. Mutation of either a
      consensus AP-1 site within intron 8 or the Sp1 site in the promoter reduced PMA
      induced activity by 80-100%. Gel shift assays using the intron 8 AP-1 sequence
      demonstrated the formation of an AP-1-specific DNA-protein complex. Our results
      suggest that inducible PGHS-1 gene expression involves the coordinate functioning
      of a Sp1 site in the promoter and an AP-1 site in intron 8.

PMID- 16105650
TI  - Reversing chemoresistance in cisplatin-resistant human ovarian cancer cells: a
      role of c-Jun NH2-terminal kinase 1.
AB  - To investigate the role of activation of c-Jun NH2-terminal kinase 1 (JNK1) in
      mediating cisplatin-induced apoptosis and the possibility of induction of JNK
      activity in triggering relation to DNA damage and drug resistance. We
      investigated the difference of cisplatin-induced activation of JNK pathway and
      H2O2 alteration between cisplatin-sensitive human ovarian carcinoma cell line
      A2780 and its resistant variant A2780/DDP. JNK, p-JNK protein, and extracellular
      H2O2 levels were determined in both A2780 and A2780/DDP cells which were
      transfected with dominant negative allele of JNK and recombinant JNK1 separately.
      Both A2780 and A2780/DDP were treated with CDDP, the JNK pathway was activated
      and a prolonged JNK activation was maintained for at least 12 h in A2780, and
      only a transient activation (3 h) was detected in A2780/DDP in response to
      cisplatin treatment. Inhibition of JNK activity by transfection with a dominant
      negative allele of JNK blocked CDDP-induced apoptosis significantly in A2780
      cells. Selective stimulation of the JNK pathway by lipofectamine-mediated
      delivery of recombinant JNK1 led to activation of c-Jun and decrease of
      extracellular H2O2, as well as apoptosis sensitization to CDDP in A2780/DDP
      cells. We concluded that JNK pathway might play an important role in mediating
      cisplatin-induced apoptosis in A2780 cells, and the duration of JNK activation
      might be critical in determining whether cells survive or undergo apoptosis. The
      resistance to CDDP can be reversed through activating c-Jun and decreasing
      extracellular generation of H2O2 by pcDNA3(FLAG)-JNK1-wt transfection in
      A2780/DDP cells.

PMID- 16105651
TI  - Regulatory mechanism of tyrosine hydroxylase activity.
AB  - Activity of tyrosine hydroxylase is regulated by feedback inhibition and
      inactivation by catecholamines, and activation by protein phosphorylation. In
      this article, reaction mechanisms for the conversion of tyrosine hydroxylase to
      an inactive/stable form by catecholamines, and activation of tyrosine hydroxylase
      by phosphorylation at Ser-40 are discussed. Inactivation may be induced by sub
      stoichiometric amounts of catecholamines, and activation by phosphorylation of
      Ser-40 may require phosphorylation of three or all four subunits of a tyrosine
      hydroxylase molecule. Cooperative phosphorylation at Ser-40 in the subunits is
      also discussed.

PMID- 16105652
TI  - Hypoxia reduces constitutive and TNF-alpha-induced expression of monocyte
      chemoattractant protein-1 in human proximal renal tubular cells.
AB  - Chronic hypoxia has been reported to be associated with macrophage infiltration
      in progressive forms of kidney disease. Here, we investigated the regulatory
      effects of hypoxia on constitutive and TNF-alpha-stimulated expression of
      monocyte chemoattractant protein-1 (MCP-1) in cultured human proximal renal
      tubular cells (HPTECs). Hypoxia reduced constitutive MCP-1 expression at the mRNA
      and protein levels in a time-dependent fashion for up to 48 h. Hypoxia also
      inhibited MCP-1 up-regulation by TNF-alpha. Treatment with actinomycin D showed
      that hypoxic down-regulation of MCP-1 expression resulted mainly from a decrease
      in the transcription but not the mRNA stability. Immunoblot and
      immunofluorescence analyses revealed that treatment with hypoxia or an iron
      chelator, desferrioxamine, induced nuclear accumulation of hypoxia-inducible
      factor-1alpha (HIF-1alpha) in HPTECs. Desferrioxamine mimicked hypoxia in the
      reduction of MCP-1 expression. However, overexpression of a dominant negative
      form of HIF-1alpha did not abolish the hypoxia-induced reduction of MCP-1
      expression in HPTECs. These results suggest that hypoxia is an important negative
      regulator of monocyte chemotaxis to the renal inflamed interstitium, by reducing
      MCP-1 expression partly via hypoxia-activated signals other than the HIF-1
      pathway.

PMID- 16105653
TI  - Molecular genetics of tyrosine 3-monooxygenase and inherited diseases.
AB  - Tyrosine 3-monooxygenase (tyrosine hydroxylase, TH) catalyzes the initial and
      rate-limiting step in the catecholamine biosynthesis. Alteration in TH activity
      is involved in the pathogenesis of certain disorders derived from
      catecholaminergic dysfunction. In the present review, we focus on recent advances
      in molecular genetic study of TH function and inherited diseases. Knockout mice
      lacking TH gene show severe catecholamine depletion and perinatal lethality. Mice
      heterozygous for the TH mutation exhibit defects in some neuropsychological
      functions. Dopamine-deficient mice impair motor control and operant learning
      during postnatal development. In addition, some point mutations in the human TH
      gene underlie the inherited diseases, including the recessive form of L-DOPA
      responsive dystonia, parkinsonism in infancy, or progressive encephalopathy.
      These mutations indeed appear to reduce TH activity or influence expression of TH
      protein. Advances in molecular genetic studies provide a deeper understanding of
      the relationship between the alteration in TH activity and the pathology of
      catecholaminergic systems.

PMID- 16105654
TI  - Early years of oxygenase research in Bethesda, Osaka, Urbana, and Kanazawa.
AB  - In this brief review, I recollect my experiences of how the studies of
      pyrocatechase and salicylate hydroxylase led to the isolation and revelation of
      P450cam. Those experiences were instrumental in the separation, purification, and
      characterization of the two forms of adrenal cortex mitochondrial P450.

PMID- 16105655
TI  - Regulation of growth-blocking peptide expression during embryogenesis of the
      cabbage armyworm.
AB  - Growth-blocking peptide (GBP) is an insect cytokine with diverse biological
      functions. Northern blot analysis revealed high heterogeneity in the size
      distribution of GBP mRNAs as well as in the tissues where they are detected. The
      spatio-temporal transcription pattern is dynamic, especially during
      embryogenesis. Gel shift assays demonstrated that the cabbage armyworm embryo
      nuclear extract specifically binds to a 178-bp element, at position +234 to +411
      from the transcription start site of the 1.3 kb GBP transcript, in which two
      Drosophila Deformed (Dfd) binding sites are repeated in tandem. The specific
      binding between this element and Dfd was demonstrated using recombinant cabbage
      armyworm Dfd protein. Silencing the Dfd expression in embryos by treating with
      Dfd double-stranded RNA did not reduce the expression level of GBP, but ectopic
      GBP expression was observed in the lateral region of the embryo, suggesting that
      Dfd could serve as a transcriptional repressor for the GBP gene.

PMID- 16105656
TI  - Molecular identity and gene expression of aldosterone synthase cytochrome P450.
AB  - 11Beta-hydroxylase (CYP11B1) of bovine adrenal cortex produced corticosterone as
      well as aldosterone from 11-deoxycorticosterone in the presence of the
      mitochondrial P450 electron transport system. CYP11B1s of pig, sheep, and
      bullfrog, when expressed in COS-7 cells, also performed corticosterone and
      aldosterone production. Since these CYP11B1s are present in the zonae fasciculata
      and reticularis as well as in the zona glomerulosa, the zonal differentiation of
      steroid production may occur by the action of still-unidentified factor(s) on the
      enzyme-catalyzed successive oxygenations at C11- and C18-positions of steroid. In
      contrast, two cDNAs, one encoding 11beta-hydroxylase and the other encoding
      aldosterone synthase (CYP11B2), were isolated from rat, mouse, hamster, guinea
      pig, and human adrenals. The expression of CYP11B1 gene was regulated by cyclic
      AMP (cAMP)-dependent signaling, whereas that of CYP11B2 gene by calcium ion
      signaling as well as cAMP-signaling. Salt-inducible protein kinase, a cAMP
      induced novel protein kinase, was one of the regulators of CYP11B2 gene
      expression.

PMID- 16105657
TI  - Cyclin D3 interacts with vitamin D receptor and regulates its transcription
      activity.
AB  - D-type cyclins are essential for the progression through the G1 phase of the cell
      cycle. Besides serving as cell cycle regulators, D-type cyclins were recently
      reported to have transcription regulation functions. Here, we report that cyclin
      D3 is a new interacting partner of vitamin D receptor (VDR), a member of the
      superfamily of nuclear receptors for steroid hormones, thyroid hormone, and the
      fat-soluble vitamins A and D. The interaction was confirmed with methods of yeast
      two-hybrid system, in vitro binding analysis and in vivo co-immunoprecipitation.
      Cyclin D3 interacted with VDR in a ligand-independent manner, but treatment of
      the ligand, 1,25-dihydroxyvitamin D3, strengthened the interaction. Confocal
      microscopy analysis showed that ligand-activated VDR led to an accumulation of
      cyclin D3 in the nuclear region. Cyclin D3 up-regulated transcriptional activity
      of VDR and this effect was counteracted by overexpression of CDK4 and CDK6. These
      findings provide us a new clue to understand the transcription regulation
      functions of D-type cyclins.

PMID- 16105658
TI  - Vascular endothelial growth factor receptors in osteoclast differentiation and
      function.
AB  - Osteoclasts are derived from haematopoietic stem cell precursors of the
      monocyte/macrophage cell lineage, through interaction with factors that are
      believed to include M-CSF and RANKL. VEGF is a proangiogenic cytokine that has
      been shown to promote osteoclast differentiation and survival. In this study, we
      assessed the role of VEGF and its receptors in osteoclastogenesis, in vitro, by
      culturing osteoclast precursors in the presence of VEGF, VEGF receptor-specific
      ligands, and blocking antibodies to VEGF receptors. Activation of VEGFR1 in the
      presence of RANKL induces osteoclast differentiation. Stimulating the receptors
      individually induced increased resorption by osteoclasts compared to controls but
      not to the level observed when stimulating both receptors simultaneously. We have
      shown that VEGF induces osteoclast differentiation through its action on VEGFR1.
      The way in which VEGF mediates its effect on mature osteoclast activity, however,
      may be through its interaction with both receptor subtypes.

PMID- 16105659
TI  - In vitro study of malaria parasite induced disruption of blood-brain barrier.
AB  - The mechanism of blood-brain barrier breakdown in the complex pathogenesis of
      cerebral malaria is not well understood. In this study, primary cultures of
      porcine brain capillary endothelial cells (PBCEC) were used as in vitro model.
      Membrane-associated malaria antigens obtained from lysed Plasmodium falciparum
      schizont-infected erythrocytes stimulated human peripheral blood mononuclear
      cells (PBMC) to secrete tumor necrosis factor alpha. In co-cultivation with the
      brain endothelial cell model, the malaria-activated PBMC stimulated the
      expression of E-selectin and ICAM-1 on the PBCEC. Using electric cell-substrate
      impedance sensing, we detected a significant decrease of endothelial barrier
      function within 4h of incubation with the malaria-activated PBMC.
      Correspondingly, immunocytochemical studies showed the disruption of tight
      junctional complexes. Combination of biochemical and biophysical techniques
      provides a promising tool to study changes in the blood-brain barrier function
      associated with cerebral malaria. Moreover, it is shown that the porcine
      endothelial model is able to respond to human inflammatory cells.

PMID- 16105660
TI  - HIV protease inhibitor ritonavir increases endothelial monolayer permeability.
AB  - HIV protease inhibitors (PIs) are often associated with metabolic and
      cardiovascular complications although they are effective anti-HIV drugs. In this
      study, we determined whether HIV PI ritonavir could increase endothelial
      permeability, one of the important mechanisms of vascular lesion formation. Human
      dermal microvascular endothelial cells (HMECs) treated with ritonavir showed a
      significant increase of endothelial permeability in a dose- and time-dependent
      manner assayed with a transwell system. Ritonavir significantly reduced the mRNA
      levels of tight junction proteins zonula occluden-1, occludin, and claudin-1 by
      40-60% as compared to controls (P<0.05) by real-time PCR analysis. Protein levels
      of these tight junction molecules were also substantially reduced in the
      ritonavir-treated cells. In addition, HMECs treated with ritonavir (7.5, 15, and
      30microM) showed a substantial increase of superoxide anion production by 10%,
      32%, and 65%, respectively, as compared to controls. Antioxidants (EGCG and
      SeMet) effectively reduced ritonavir-induced endothelial permeability.
      Furthermore, ritonavir activated ERK1/2 (phosphorylation), but not P38 and JNK.
      Specific ERK1/2 inhibitor, PD89059, significantly abolished ritonavir-induced
      endothelial permeability by 92%. Thus, HIV PI ritonavir increases endothelial
      permeability, decreases levels of tight junction proteins, and increases
      superoxide anion production. ERK1/2 activation is involved in the signal
      transduction pathway of ritonavir-induced endothelial permeability.

PMID- 16105661
TI  - Acetylcholine stimulates cyclic ADP-ribose formation via M1 muscarinic receptors
      in rat superior cervical ganglion.
AB  - The role of cyclic ADP-ribose (cADPR) as the downstream signal of neuronal
      muscarinic acetylcholine receptors (mAChRs) and the enzyme responsible for its
      synthesis, ADP-ribosyl cyclase, were examined in the rat superior cervical
      ganglion (SCG). Application of acetylcholine or other mAChR agonists increased
      the ADP-ribosyl cyclase activity by about 250-300% in crude membrane fractions
      from the SCG of 14-day-old rats. This effect was inhibited by atropine or by the
      M1-mAChR antagonist, pirenzepine, and was mimicked by GTP. These results indicate
      that the M1 mAChRs couple to the membrane-bound form of ADP-ribosyl cyclase and
      suggest that cADPR is a second messenger of M1 mAChR signaling in nervous tissue.

PMID- 16105662
TI  - Global gene expression response to telomerase in bovine adrenocortical cells.
AB  - The infinite proliferative capability of most immortalized cells is dependent
      upon the presence of the enzyme telomerase and its ability to maintain telomere
      length and structure. However, telomerase may be involved in a greater system
      than telomere length regulation, as recent evidence has shown it capable of
      increasing wound healing in vivo, and improving cellular proliferation rate and
      survival from apoptosis in vitro. Here, we describe the global gene expression
      response to ectopic telomerase expression in an in vitro bovine adrenocortical
      cell model. Telomerase-immortalized cells showed an increased ability for
      proliferation and survival in minimal essential medium above cells transgenic for
      GFP. cDNA microarray analyses revealed an altered cell state indicative of
      increased adrenocortical cell proliferation regulated by the IGF2 pathway and
      alterations in members of the TGF-B family. As well, we identified alterations in
      genes associated with development and wound healing that support a model that
      high telomerase expression induces a highly adaptable, progenitor-like state.

PMID- 16105663
TI  - Gastric inhibitory polypeptide modulates adiposity and fat oxidation under
      diminished insulin action.
AB  - Gut hormone gastric inhibitory polypeptide (GIP) stimulates insulin secretion
      from pancreatic beta-cells upon ingestion of nutrients. Inhibition of GIP
      signaling prevents the onset of obesity and consequent insulin resistance induced
      by high-fat diet. In this study, we investigated the role of GIP in accumulation
      of triglycerides into adipocytes and in fat oxidation peripherally using insulin
      receptor substrate (IRS)-1-deficient mice and revealed that IRS-1(-/-)GIPR(-/-)
      mice exhibited both reduced adiposity and ameliorated insulin resistance.
      Furthermore, increased gene expression of CD36 and UCP2 in liver, and increased
      expression and enzyme activity of 3-hydroxyacyl-CoA dehydrogenase in skeletal
      muscle of IRS-1(-/-)GIPR(-/-) mice might contribute to the lower respiratory
      quotient and the higher fat oxidation in light phase. These results suggest that
      GIP plays a crucial role in switching from fat oxidation to fat accumulation
      under the diminished insulin action as a potential target for secondary
      prevention of insulin resistance.

PMID- 16105664
TI  - LTB4 stimulates growth of human pancreatic cancer cells via MAPK and PI-3 kinase
      pathways.
AB  - We have previously shown the importance of LTB4 in human pancreatic cancer. LTB4
      receptor antagonists block growth and induce apoptosis in pancreatic cancer cells
      both in vitro and in vivo. Therefore, we investigated the effect of LTB4 on
      proliferation of human pancreatic cancer cells and the mechanisms involved. LTB4
      stimulated DNA synthesis and proliferation of both PANC-1 and AsPC-1 human
      pancreatic cancer cells, as measured by thymidine incorporation and cell number.
      LTB4 stimulated rapid and transient activation of MEK and ERK1/2 kinases. The MEK
      inhibitors, PD98059 and U0126, blocked LTB4-stimulated ERK1/2 activation and cell
      proliferation. LTB4 also stimulated phosphorylation of p38 MAPK; however, the p38
      MAPK inhibitor, SB203580, failed to block LTB4-stimulated growth. The activity of
      JNK/SAPK was not affected by LTB4 treatment. Phosphorylation of Akt was also
      induced by LTB4 and this effect was blocked by the PI-3 kinase inhibitor
      wortmannin, which also partially blocked LTB4-stimulated cell proliferation. In
      conclusion, LTB4 stimulates proliferation of human pancreatic cancer cells
      through MEK/ERK and PI-3 kinase/Akt pathways, while p38 MPAK and JNK/SAPK are not
      involved.

PMID- 16105665
TI  - MDR1 gene expression enhances long-term engraftibility of cultured bone marrow
      cells.
AB  - Primitive hematopoietic stem cells are responsible for long-term engraftment in
      irradiated host. Here, we report that multi-drug resistance 1 (mdr1) gene
      expressing primitive hematopoietic cells were multiplied in ex vivo culture, with
      the support of extracellular matrix components and cytokines. About 20-fold
      expansion of total nucleated cells was achieved in a 10-day culture. Lin(-)Sca
      1(+) and long-term culture-initiating cells were increased by 54- and 26-fold,
      respectively. Expanded cells were long-term multi-lineage engraftible in sub
      lethally irradiated mice. Donor-derived peripheral blood chimerism was
      significantly higher (73.2+/-9.1%, p<0.01) in expanded cells than in normal and 5
      flurouracil-treated bone marrow cells. Most interestingly, the expression of mdr1
      gene was significantly enhanced in cultured cells than in other two sources of
      donor cells. The mdr1 gene was functional since expanded cells effluxed Hoechst
      33342 and Rh123 dyes. These results suggest that primitive engraftible stem cells
      can be expanded in the presence of suitable microenvironments.

PMID- 16105666
TI  - NO-donating aspirin inhibits both the expression and catalytic activity of
      inducible nitric oxide synthase in HT-29 human colon cancer cells.
AB  - Nitric oxide-releasing aspirin (NO-ASA) is emerging as a potentially important
      chemopreventive agent against colon cancer. We examined in HT-29 human colon
      adenocarcinoma cells the effect of NO-ASA on the inducible form of nitric oxide
      synthase (NOS2), an enzyme implicated in colon carcinogenesis. NO-ASA inhibited
      in a time- and concentration-dependent manner the expression of NOS2 up to 70%
      compared to control (IC50 for this effect = 46 microM). NO-ASA also decreased the
      corresponding steady-state mRNA levels and this reduction preceded the reduction
      of protein levels by at least 6 h. NO-ASA also reduced the enzymatic activity of
      NOS2, as determined by a direct enzyme assay (maximal reduction = 80%) and by
      determining the accumulation of NO in the culture medium (IC50 for this effect =
      36 microM). These effects of NO-ASA on NOS2 were paralleled by inhibition in cell
      growth (IC50 = 8.5 microM). These findings indicate that NO-ASA profoundly
      inhibits both the expression and enzymatic activity of NOS2 and suggest that
      these effects may represent an important mechanism for the colon cancer
      chemopreventive effect of NO-ASA.

PMID- 16105667
TI  - Iron-mediated free-radical formation of signaling lipids in a model system.
AB  - It has been shown using matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS) and its combination with thin-layer
      chromatography (TLC) that the action of the ascorbate/Fe(2+)/H(2)O(2) oxidizing
      system on cardiolipin and galactocerebroside results in the formation of
      phosphatidic acid (PA) and ceramide (Cer), respectively. These data, when
      combined with results obtained on radiolysis of similar substances, allowed the
      conclusion that the formation of PA and Cer occurs via an OH-induced
      fragmentation taking place in polar moiety of the starting substrates.

PMID- 16105668
TI  - Health promotion behaviors and quality of life among community-dwelling elderly
      in Korea: a cross-sectional survey.
AB  - As individuals live longer, health promotion behaviors become even more
      important, particularly with regard to maintaining functional independence and
      improving quality of life (QoL). The purpose of this study was to explore the
      relationship between health promotion behaviors and QoL in Korean elderly living
      in the community. This study was a descriptive-correlational study to explore the
      relationship between health promotion behaviors and QoL among the community
      dwelling elderly in Korea. A convenience sample of 2000 community residents who
      were over 65 years old and cognitively intact were selected from 32 senior
      centers and 242 public health centers in Korea. A total of 1920 were included in
      the analyses, following the exclusion of 80 incomplete questionnaires and subject
      refusals. Participants who consented to participate in the study were interviewed
      by trained interviewers with a structured questionnaire. The results of the study
      showed that there were statistically significant differences in QoL of the
      elderly related to exercise participation, alcohol abstinence and blood pressure
      (BP) check-up (p<.05). Multiple regression analysis revealed that perceived
      health status, number of chronic illnesses, activities of daily living, BP
      checkup, exercise, and gender were statistically significant predictors of QoL.
      R(2) for this whole regression model was .412, indicating that approximately
      41.2% of the variance in QoL was accounted for by the linear combination of these
      variables. Nurses should enhance the QoL in elderly persons by facilitating
      health promotion behaviors through formal nursing interventions which will
      maintain and increase a healthy and active life.

PMID- 16105669
TI  - Linguistic constraints on literacy development: introduction to the special
      issue.

PMID- 16105670
TI  - The diffusive vesicle supply center model for tip growth in fungal hyphae.
AB  - We propose the diffusive vesicle supply center model for tip growth in fungal
      hyphae. The model is based on the three-dimensional vesicle supply center (VSC)
      model [Gierz, G., Bartnicki-Garcia, S., 2001. A three-dimensional model of fungal
      morphogenesis based on the vesicle supply center concept: J. Theor. Biol. 208,
      151-164], but incorporates two aspects of a more realistic vesicle delivery
      mechanism: vesicle diffusion from the VSC and a finite rate constant for vesicle
      fusion with the cell membrane. We develop a framework to describe tip growth for
      a general class of models based on the vesicle supply center concept. Combining
      this with a method for calculating the steady state distribution of diffusive
      vesicles we iteratively solve for stationary cell shapes. These show a blunter
      tip than predicted by the original VSC model, which we attribute to increased
      forward-directed vesicle delivery via diffusion. The predicted distance between
      the VSC and the utmost tip of the cell is set by the ratio between the diffusion
      constant and the rate constant for vesicle exocytosis. Combined with the cell
      radius, these define the only dimensionless parameter for our model.

PMID- 16105671
TI  - Involvement of DNA helicases in chromate resistance by Pseudomonas aeruginosa
      PAO1.
AB  - Chromate-hypersensitive mutants of the Pseudomonas aeruginosa PAO1 strain were
      isolated using transposon insertion mutagenesis. Comparison of the nucleotide
      sequences of the regions interrupted within the PAO1 genome showed that mutant
      strains GGP-64 and AJ-22 were affected in open reading frames PA0967 and PA5345,
      which correspond to the ruvB and recG genes, respectively. These genes encode
      helicases RuvB and RecG involved in DNA replication, recombination and repair.
      The chromate resistance phenotype in mutants GGP-64 and AJ-22 was restored by
      cosmids bearing wild type ruvB or recG genes, respectively. Also, both mutant
      strains showed an increased susceptibility to the toxic oxyanions tellurite and
      selenite as well as to mitomycin C, but not to arsenite, paraquat and hydrogen
      peroxide. It was concluded that P. aeruginosa RuvB and RecG helicases are
      involved in repairing DNA damage caused by chromate or its derivatives.

PMID- 16105672
TI  - Dermal excisional wound healing in pigs following treatment with topically
      applied pure oxygen.
AB  - Hypoxia, caused by disrupted vasculature and peripheral vasculopathies, is a key
      factor that limits dermal wound healing. Factors that can increase oxygen
      delivery to the regional tissue, such as supplemental oxygen, warmth, and
      sympathetic blockade, can accelerate healing. Clinical experience with adjunctive
      hyperbaric oxygen therapy (HBOT) in the treatment of chronic wounds have shown
      that wound hyperoxia may increase granulation tissue formation and accelerate
      wound contraction and secondary closure. However, HBOT is not applicable to all
      wound patients and may pose the risk of oxygen toxicity. Thus, the efficacy of
      topical oxygen treatment in an experimental setting using the pre-clinical model
      involving excisional dermal wound in pigs was assessed. Exposure of open dermal
      wounds to topical oxygen treatment increased tissue pO2 of superficial wound
      tissue. Repeated treatment accelerated wound closure. Histological studies
      revealed that the wounds benefited from the treatment. The oxygen treated wounds
      showed signs of improved angiogenesis and tissue oxygenation. Topically applied
      pure oxygen has the potential of benefiting some wound types. Further studies
      testing the potential of topical oxygen in pre-clinical and clinical settings are
      warranted.

PMID- 16105673
TI  - Biological motion processing in adolescents with early periventricular brain
      damage.
AB  - The developing brain is traditionally viewed to possess a great compensatory
      potential. Here we ask whether visual processing of point-light displays
      depicting human walking is compromised in adolescents who were born premature
      (between 27 and 33 gestation weeks) and suffer early bilateral damage to
      periventricular brain regions. Combining psychophysics with volumetric analysis
      of structural magnetic resonance imaging (MRI), we found that even relatively
      small periventricular parieto-occipital lesions may result in long-lasting
      breakdown of visual processing of point-light displays. Analysis of receiver
      operating characteristic (ROC) curves revealed higher susceptibility of the
      patients' perceptual system to camouflage of a point-light figure. The lack of
      difference in sensitivity between former preterms with normal MRI scan and term
      born controls indicates that perceptual deficiencies in patients with
      periventricular leukomalacia (PVL) are not simply due to premature birth. Most
      importantly, sensitivity in patients even with mild PVL was lower than in both
      control groups. Display 180 degrees inversion in the image plane, which is known
      to impair processing of point-light displays, resulted in a substantial reduction
      of sensitivity so that it no longer differed between the groups. Despite the
      social and ecological significance of human locomotion, the capacity of the brain
      to detect biological motion is substantially modulated by periventricular lesions
      even if they occur very early in life. The findings point to specific
      restrictions on the brain's spontaneous compensatory plasticity in perceptual
      development.

PMID- 16105674
TI  - The Refractive Status and Vision Profile: evaluation of psychometric properties
      and comparison of Rasch and summated Likert-scaling.
AB  - The psychometric properties of the Refractive Status and Vision Profile (RSVP)
      questionnaire were evaluated using Rasch analysis. Ninety-one myopic patients
      from a refractive surgery clinic and general optometric practice completed the
      RSVP. Rasch analysis of the RSVP ordinal data was performed to examine for
      unidimensionality and item reduction. The traditional Likert-scoring system was
      compared with a Rasch-scored RSVP and a reduced item Rasch-scored RSVP. Rasch
      analysis of the original RSVP showed poor targeting of item difficulty to patient
      quality of life, items with a ceiling effect and underutilized response
      categories. Combining the underutilized response scales and removal of redundant
      and misfitting items improved the internal consistency and targeting of the RSVP,
      and the reduced 20-item Rasch scored RSVP showed greater relative precision over
      standard Likert scoring in discriminating between the two subject groups. A Rasch
      scaled quality of life questionnaire is recommended for use in refractive
      outcomes research.

PMID- 16105675
TI  - Developing an optimal river typology for biological elements within the Water
      Framework Directive.
AB  - The Water Framework Directive requires a river classification based on
      environmental variables (a typology) to be created as a structure for reporting
      ecological status. A single permutation procedure, utilising the same variables
      repeatedly but with different categorical divisions, enabled both the choice of
      variables and the boundary divisions for these variables to be optimised
      simultaneously in the development of the typology. This, in addition to a data
      set which appropriately combined different biological elements, enabled a
      typology to be developed which was far more effective than a System A, CCA
      derived or expert opinion-based typology in segregating communities. This optimal
      typology could be used to improve the performance of ecological quality
      assessment methods.

PMID- 16105676
TI  - Respiratory burst and NAD(P)H oxidase activity are involved in capacitation of
      cryopreserved bovine spermatozoa.
AB  - Heparin (a glycosaminoglycan) and quercetin (a calcium-ATPase plasma membrane
      specific inhibitor) induce bovine sperm capacitation. Mitochondria from frozen
      semen are capable of generating oxidative energy. The aim of the study was to
      determine oxygen uptake variation and the participation of diphenileneiodonium
      (DPI)-sensitive oxidases from spermatozoa capacitated with heparin or quercetin.
      Oxygen uptake was measured polarographically and 2 microM diphenileneiodonium
      (DPI) was used as a specific inhibitor of NAD(P)H-oxidases. Sperm capacitation
      was determined by the chlorotetracycline technique. Heparin produced a
      respiratory burst (17.0+/-3.2 microL O2/h/10(8) spermatozoa; mean+/-S.D.) versus
      control (11.3+/-0.9 microL O2/h/10(8) spermatozoa; P<0.05). Oxygen uptake and
      sperm hypermotility were inhibited by cyanide. Treatment with DPI blocked heparin
      capacitation and oxygen uptake (cyanide-sensitive) decreased to control levels.
      Respiration of quercetin-treated samples (cyanide-sensitive; 9.7+/-0.7 microL
      O2/h/10(8) spermatozoa) was not significantly different from the controls; oxygen
      uptake was not modified by DPI, but quercetin capacitation was inhibited
      (P<0.05). The effect of DPI with heparin confirmed that oxidases participate in
      capacitation induction. The addition of superoxide dismutase and/or catalase to
      heparin- or quercetin-treated samples, failed to modify oxygen uptake and blocked
      capacitation (P<0.05), suggesting that the superoxide anion (O2*-) participates
      in the capacitation induction. High mitochondrial activity from heparin-treated
      samples indicated that energy requirements, especially for hypermotility, were
      supported by the respiratory chain. Although a respiratory burst was not produced
      by quercetin, DPI-sensitive-oxidases (O2*- source) were necessary for
      capacitation. In cryopreserved bovine spermatozoa, heparin- or quercetin-induced
      capacitation required different levels of mitochondrial energy and DPI-sensitive
      oxidase activity.

PMID- 16105677
TI  - The kinase inhibitor indirubin-3'-oxime prevents germinal vesicle breakdown and
      reduces parthenogenetic development of pig oocytes.
AB  - Oocytes undergo spontaneous germinal vesicle breakdown (GVBD) after being
      released from the follicular environment; this potentially prevents manipulation
      of the oocyte at the germinal vesicle (GV) stage. The objectives of this study
      were to investigate the effects of indirubin, a potent cdc2 kinase inhibitor, on
      GVBD and microtubular structure of porcine oocytes. Cumulus-oocyte-complexes
      (COCs) were collected from abattoir-derived ovaries and were randomly allocated
      to different concentrations of indirubin treatments (0, 10, 25, 50, and 100
      microM in Experiment 1 and 0, 50, 75, and 100 microM in Experiment 2) during 44 h
      of IVM. The influences on the GVBD, microtubules, and maturation rates were
      evaluated using epifluorescence microscopy. The percentages of oocytes remaining
      at the GV stage were 0, 16, 26, 69, and 85% for oocytes treated with 0, 10, 25,
      50, and 100 microM of indirubin, respectively, which differed among treatment
      groups (P<0.05). However, there were no significant differences between the
      oocytes treated with 75 and 100 microM (79 and 81%). The cytoplasmic microtubules
      were fragmented in oocytes maintained at the GV stage and the chromatin became
      condensed or aggregated. When COCs were incubated with indirubin (50-75 microM)
      for 22 h and then transferred to maturation medium for 44 h (Experiments 3-5),
      the percentages of oocytes reaching the metaphase II stage were generally higher
      than when the COCs were cultured in the presence of the drug for 44 h (62-65%
      versus 44-46%). However, the parthenogenetic development of the oocytes in
      Experiment 6 was reduced significantly in drug-treated oocytes. In summary,
      treatment with 50-75 microM of indirubin effectively prevented GVBD in porcine
      oocytes, but the developmental competence of the oocytes was compromised.

PMID- 16105678
TI  - Medicinal plants: traditions of yesterday and drugs of tomorrow.
AB  - Plants have provided Man with all his needs in terms of shelter, clothing, food,
      flavours and fragrances as not the least, medicines. Plants have formed the basis
      of sophisticated traditional medicine systems among which are Ayurvedic, Unani,
      Chinese amongst others. These systems of medicine have given rise to some
      important drugs still in use today. Among the lesser-known systems of medicines
      are the African and Australian, Central and South American amongst others. The
      search for new molecules, nowadays, has taken a slightly different route where
      the science of ethnobotany and ethnopharmacognosy are being used as guide to lead
      the chemist towards different sources and classes of compounds. It is in this
      context that the flora of the tropics by virtue of its diversity has a
      significant role to play in being able to provide new leads. Nonetheless the
      issue of sovereignty and property rights should also be addressed in line with
      the Convention for Biological Diversity (CBD). This paper highlights the above,
      provides an overview of the classes of molecules present in plants and gives some
      examples of the types of molecules and secondary metabolites that have led to the
      development of these pharmacologically active extracts. The paper also presents
      some data on the use of plant products in the development of functional foods,
      addresses the needs for validation of plant extracts and always stressing on
      safety, efficacy and quality of phyto-medications.

PMID- 16105679
TI  - Selenium, oxidative stress, and health aspects.
AB  - Metabolic processes which generate oxidants and antioxidants are governed by
      genetic disposition as well as environmental factors. Changes in lifestyle,
      including increased environmental pollution, sun exposure, and dietary habits
      modify the challenge of the organism by reactive oxygen species. Defense
      mechanisms are reinforced by increasing dietary intake of antioxidants and
      micronutrients such as vitamins and selenium (Se). Se deficiency has been
      recognized to promote some disease states. Epidemiological findings link a
      lowered Se status to neurodegenerative and cardiovascular diseases as well as to
      increased cancer risk. While evidence exists to suggest that additional
      selenocompounds would be beneficial in some health conditions, results from
      future intervention trials are needed to substantiate the argument for increasing
      Se intake. Several pieces of the puzzle concerning the molecular mechanisms
      underlying the reactive oxygen species-triggered disease state and intervention
      by enzymatic antioxidants have been elucidated. A novel concept of protection of
      stromal cells against the dominating influence of tumor cells in tumor-stroma
      interaction by selenocompounds and other antioxidants is presented herein, which
      may translate into therapeutic strategies in chemoprevention of tumor invasion.

PMID- 16105680
TI  - Are tattooing and body piercing indicators of risk-taking behaviours among high
      school students?
AB  - PURPOSE: To date, studies pertaining to possible links between body modification
      and risk-taking behaviours have been conducted mainly among targeted groups. The
      objective of this study is to examine the influence of a number of risk-taking
      behaviours on the probability of being pierced or tattooed among a general
      adolescent population. METHODS: Data come from a cross-sectional study conducted
      among a sample of 2180 students aged 12-18. Data were collected directly from
      students through a self-report survey. RESULTS: Findings confirm the "risky"
      nature of these practices even though the tattooed and pierced subjects of this
      study were from a general adolescent population. Factors that contribute
      significantly to the likelihood of teenagers being tattooed or pierced, for both
      genders, are associated with "externalized risk behaviours" such as multiple drug
      use, illegal activities, gang affiliation, problem gambling, school truancy and
      rave attendance. CONCLUSION: Nowadays, tattooing and body piercing are perceived
      by many as body decoration, increasingly belonging to the realm of generational
      conformity. Contrary to this view, our results suggest that these practices among
      adolescents are mostly adopted by those who are involved in various deviant or
      illegal activities, which are often interrelated.

PMID- 16105681
TI  - Polysulfone-graft-poly(ethylene glycol) graft copolymers for surface modification
      of polysulfone membranes.
AB  - Amphiphilic graft copolymers having polysulfone (PSf) backbones and poly(ethylene
      glycol) (PEG) side chains were synthesized via reaction of an alkoxide formed
      from PEG and a base (sodium hydride) with chloromethylated polysulfone. The
      resulting polysulfone-graft-poly(ethylene glycol), PSf-g-PEG, materials were
      hydrophilic but water insoluble, rendering them potentially useful as biomaterial
      coatings. PSf-g-PEG films exhibited high resistance to protein adsorption and
      cell attachment. When used as an additive in PSf membranes prepared by immersion
      precipitation, the graft copolymer preferentially segregates to the membrane
      surface, delivering enhanced wettability, porosity and protein resistance
      compared to unmodified PSf membranes. The surface properties of PSf-g-PEG
      modified membranes render them desirable candidates for hemodialysis.

PMID- 16105682
TI  - Mechanisms of decrease in fatigue crack propagation resistance in irradiated and
      melted UHMWPE.
AB  - Adhesive/abrasive wear in ultra-high molecular weight polyethylene (UHMWPE) has
      been minimized by radiation cross-linking. Irradiation is typically followed by
      melting to eliminate residual free radicals that cause oxidative embrittlement.
      Irradiation and subsequent melting reduce the strength and fatigue resistance of
      the polymer. We determined the radiation dose dependence and decoupled the
      effects of post-irradiation melting on the crystallinity, mechanical properties
      and fatigue crack propagation resistance of room temperature irradiated UHMWPE
      from those of irradiation alone. Stiffness and yield strength, were largely not
      affected by increasing radiation dose but were affected by changes in
      crystallinity, whereas plastic properties, ultimate tensile strength and
      elongation at break, were dominated at different radiation dose ranges by changes
      in radiation dose or crystallinity. Fatigue crack propagation resistance was
      shown to decrease with increase in radiation dose and with decrease in
      crystalline content. Morphology of fracture surfaces revealed loss of ductility
      with increase in radiation dose and more detrimental effects on ductility at
      lower radiation doses after post-irradiation melting.

PMID- 16105683
TI  - Glial calcium signaling and neuron-glia communication.
AB  - The existence of bidirectional signaling between astrocytes and neurons has
      revealed an important active role of astrocytes in the physiology of the nervous
      system. As a consequence, there is a new concept of the synaptic physiology-"the
      tripartite synapse", where astrocytes exchange information with the pre- and
      postsynaptic elements and participate as dynamic regulatory elements in
      neurotransmission. The control of the Ca2+ excitability in astrocytes is a key
      element in this loop of information exchange. The ability of astrocytes to
      respond to neuronal activity and discriminate between the activity of different
      synapses, the modulation of the astrocytic cellular excitability by the synaptic
      activity, and the expression of cellular intrinsic properties indicate that
      astrocytes are endowed with cellular computational characteristics that process
      synaptic information. Therefore, we propose that astrocytes can be considered as
      cellular elements involved in the information processing by the nervous system.

PMID- 16105684
TI  - Modulating sarco(endo)plasmic reticulum Ca2+ ATPase 2 (SERCA2) activity: cell
      biological implications.
AB  - Of the three mammalian members belonging to the sarco(endo)plasmic reticulum Ca2+
      ATPase (SERCA) family, SERCA2 is evolutionary the oldest and shows the most wide
      tissue-expression pattern. Two major SERCA2 splice variants are well
      characterized: the muscle-specific isoform SERCA2a and the housekeeping isoform
      SERCA2b. Recently, several interacting proteins and post-translational
      modifications of SERCA2 were identified which may modulate the activity of the
      Ca2+ pump. This review aims to give an overview of the vast literature concerning
      the cell biological implications of the SERCA2 isoform diversity and the factors
      regulating SERCA2. Proteins reported to interact with SERCA2 from the cytosolic
      domain involve the anti-apoptotic Bcl-2, the insulin receptor substrates IRS1/2,
      the EF-hand Ca2+-binding protein S100A1 and acylphosphatase. We will focus on the
      very particular position of SERCA2 as an enzyme functioning in a thin, highly
      fluid, leaky and cholesterol-poor membrane. Possible differential interactions of
      SERCA2b and SERCA2a with calreticulin, calnexin and ERp57, which could occur
      within the lumen of the endoplasmic reticulum will be discussed. Reported post
      translational modifications possibly affecting pump activity involve N
      glycosylation, glutathionylation and Ca2+/calmodulin kinase II-dependent
      phosphorylation. Finally, the pronounced vulnerability to oxidative damage of
      SERCA2 appears to be pivotal in the etiology of various pathologies.

PMID- 16105685
TI  - Two enhancements of the gravity algorithm for multiple spike train analysis.
AB  - The gravity method for neuronal assembly analysis represents each neuron as a
      particle in N-space with a time varying charge that is a filtered version of the
      corresponding spike train, with appropriate rules for forces between and
      movements of the charged particles. Resulting trajectories reflect neuronal
      timing relationships. The usual short time constants in the filter restrict
      aggregation to highly synchronized neurons and reduce the sensitivity for delayed
      correlations; long time constants in the filter reduce selectivity. Here we
      describe an enhancement that modifies rules for assigning charge increment times
      to allow mixtures of short and long lag correlations. Charge increments for each
      pair are offset from the actual spike times by time lags defined by features in
      corresponding cross-correlograms; no such charge offsets are invoked if the
      correlogram is flat. Tuning increases charge products and aggregation of long lag
      correlated pairs. A second enhancement uses a new three-dimensional display of
      particle pair trajectories to parse the type of neuronal relationship. For each
      pair, we record and display the inter-particle distance and the distance each
      particle moves from its original location in the N-space. The resulting
      trajectories cluster according to the type of interaction between the represented
      neurons. Results from simulated networks and in vivo multi-site recordings show
      that these modifications detect assembly properties not identified by the
      standard methods.

PMID- 16105686
TI  - Estimation of cortical silent period following transcranial magnetic stimulation
      using a computerised cumulative sum method.
AB  - The cortical silent period (CSP) following transcranial magnetic stimulation
      (TMS) of the motor cortex can be used to measure intra-cortical inhibition and
      changes in a number of important pathologies affecting the central nervous
      system. The main drawback of this technique has been the difficulty in accurately
      identifying the onset and offset of the cortical silent period leading to inter
      observer variability. We developed an automated method based on the cumulative
      sum (Cusum) technique to improve the determination of the duration and area of
      the cortical silent period. This was compared with experienced raters and two
      other automated methods. We showed that the automated Cusum method reliably
      correlated with the experienced raters for both duration and area of CSP.
      Compared with the automated methods, the Cusum also showed the strongest
      correlation with the experienced raters. Our results show the Cusum method to be
      a simple, graphical and powerful method of detecting low-intensity CSP that can
      be easily automated using standard software.

PMID- 16105687
TI  - Characterization of an improved procedure for the removal of microglia from
      confluent monolayers of primary astrocytes.
AB  - Cultures of astrocytes can be readily established and are widely used to study
      the biological functions of these glial cells in isolation. Unfortunately,
      contamination by microglia can confound results from such studies. Herein, a
      simple and highly effective modification of a common procedure to remove
      microglia from astrocyte cultures is described. After becoming confluent,
      astrocytes were exposed to a mitotic inhibitor for 5-6 days then treated with 50
      75 mM l-leucine methyl ester (LME) for 60-90 min. Unlike previous protocols that
      employed lower LME concentrations on subconfluent cultures or during passage of
      astrocytes, this protocol effectively depleted microglia from high-density
      astrocyte monolayers. This was evidenced by the selective depletion of microglial
      specific markers. Purified monolayers appeared morphologically normal 24h after
      LME treatment and expressed nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2
      (COX-2) proteins upon stimulation with LPS plus IFNgamma, albeit to a lower level
      than unpurified monolayers. This difference could be attributed to removal of
      contaminating microglia from monolayers and not to astrocyte dysfunction, since
      LME treatment did not alter global protein synthesis and a reactive phenotype
      could be induced in the purified monolayers. Thus, this modified protocol
      selectively depletes microglia from high-density primary astrocyte monolayers
      without compromising their functional integrity.

PMID- 16105688
TI  - Age-related alterations to immune parameters in Labrador retriever dogs.
AB  - In order to assess age-related changes in the immune status of Labrador retriever
      dogs, leukocyte phenotypes, lymphocyte proliferative capacity, and serum antibody
      levels were measured in four cohorts of dogs, ranging from 2 to 10 years of age.
      Absolute numbers of white blood cells, lymphocytes, monocytes, granulocytes, and
      CD3+, CD4+, CD8+ and CD21+ lymphocytes significantly decreased with increasing
      age. Relative percentages of lymphocytes and CD4 cells were significantly
      decreased, and relative percentages of granulocytes and CD8 cells significantly
      increased, with age. The CD4:CD8 ratio showed a significant age-related decrease.
      Proliferative responses of T-cells to mitogens in whole-blood cultures either
      increased (Concanavalin A) or remained the same (phytohemagglutinin) with age
      when data was normalised to allow for differences in responding cell number.
      Similarly, normalised data of proliferative response to anti-CD3 stimulation
      together with phorbol 12-myristate 13-acetate showed an age-related increase.
      Serum levels of total IgA significantly increased with age whereas total IgG
      levels remained unchanged. These observations illustrate a significant change to
      a number of immune parameters with age. However, further work is required to
      determine whether the differences reported here are sufficient to cause overt or
      functional immune senescence in Labrador retriever dogs.

PMID- 16105689
TI  - Antibodies and PMBC from EIAV infected carrier horses recognize gp45 and p26
      synthetic peptides.
AB  - Equine infectious anemia virus (EIAV) is a lentivirus causing a persistent
      infection in horses characterized by recurrent febrile episodes and high levels
      of viremia associated with a novel antigenic strain of the virus. The virus
      contains two envelope glycoproteins, gp90 and gp45, and four internal proteins,
      p26, p15, p11 and p9. Considering that the most infected horses are able to
      restrict EIAV replication to very low levels and that gp45 and p26 contain highly
      conserved epitopes among lentiviruses, it would be necessary to identify those
      conserved epitopes stimulating cellular and humoral responses. The aims of this
      study were to determine if the synthetic peptides identified as gp45 (aa 523-547)
      and p26 (aa 318-346) representing two highly conserved and immunodominant regions
      of EIA virus are recognized by PBMC and antibodies to EIAV adult mixed-breed
      naturally infected carrier horses, and if these peptides are able to induce
      immune responses in mice. Antibodies from 100% of carrier horses, evaluated by
      ELISA, recognized both peptides; PBMC from 80% of carrier horses, evaluated by
      lymphoproliferation assay, recognized, at least, one peptide. Furthermore,
      immunization with 100 microg of each peptide elicited humoral and cellular
      responses in BALB/c mice, antibodies appeared at 48 or 63 days of immunization
      with gp45 or p26, respectively. Although the kinetics of gp45- and p26-specific
      antibody responses were similar, percentage of positivity was higher for gp45.
      The lymphoproliferation assay, evaluated by BrdU uptake, was higher in mice
      immunized with gp45 or p26 than in the control group (P<0.05). Based on our
      findings, we consider that both peptides could be included in an effective
      vaccine design to induce long-term immunological memory.

PMID- 16105690
TI  - Dendritic cells in germ-free and specific pathogen-free mice have similar
      phenotypes and in vitro antigen presenting function.
AB  - Dendritic cells (DC) can direct downstream T-cell responses. Although bacterial
      adjuvants are strong activators of DC in vitro, the effects of normal enteric
      bacteria on DC in vivo are not well defined. We used germ-free (GF) mice to
      determine whether enteric bacteria alter DC phenotype and ability to stimulate
      naive T cells. Surface expression of CD11c, CD86, and MHCII was measured on
      splenic and mesenteric lymph node (MLN) DC. In addition, we tested the ability of
      T-cell depleted splenocytes from mice injected with LPS to stimulate allogeneic T
      cells, as determined by cell proliferation. The absolute numbers of CD11c+ DC
      were decreased in the MLN and spleen of GF mice. Freshly isolated CD11c+ DC from
      spleens or MLN of SPF and GF mice expressed similar levels of CD86 and MHCII by
      FACS analysis. Proportions of splenic DC expressing CD4 or CD8 were not different
      in GF versus SPF mice, although the percentage of CD8alpha-/CD11b+ DC was higher
      in GF MLN. Intraperitoneal injection of LPS upregulated MHCII and CD86 to a
      similar extent on splenic DC from GF or SPF mice. Splenic antigen-presenting
      cells, as well as unseparated spleen or MLN cells, from GF or SPF mice also
      induced similar levels of T-cell proliferation in vitro. We conclude that
      commensal bacterial flora do not affect co-stimulatory molecule expression of DC
      in the spleen or MLN, which exhibit a predominantly immature phenotype. In
      addition, splenic APC from GF mice are fully competent to stimulate naive T-cell
      proliferation in vitro.

PMID- 16105691
TI  - Inhibition of the hepatitis B virus replication in vitro by an
      oligodeoxynucleotide containing cytidine-guanosine motifs.
AB  - Oligodeoxynucleotides (ODNs) containing unmethylated CpG dinucleotides within
      specific sequence contexts (CpG motifs) are known as potent activators of the
      immune system and inducers of several Th1-associated immunomodulatory cytokines.
      CpG ODNs show promise as vaccine adjuvants and immunoprotective agents in
      animals. Here, we investigated the inhibitory effects of D type CpG ODN on
      hepatitis B virus (HBV) replication in vitro. The experiments were performed in
      HepG2 2.2.15 cells, which contain an integrated tandem dimer of the HBV genome
      and are routinely used for anti-HBV study. HepG2 2.2.15 cells co-cultured with
      peripheral blood mononuclear cells (PBMCs) plus CpG ODN for 3 days, remarkably
      reduced the secretion of HBsAg and HBeAg, when compared to cells treated with
      PBMCs plus non-CpG ODN. The levels of intracellular HBV DNA and HBV mRNA were
      also decreased. Treatment of HepG2 2.2.15 cells with the culture supernatants of
      PBMCs activated by CpG ODN can remarkably suppress the secretion of HBsAg and
      HBeAg as compared with that of PBMCs without CpG ODN activation under the same
      conditions. There were no inhibitory effects on the replication of HBV to be
      found for CpG ODN treatment alone. These results suggest that CpG ODN can inhibit
      indirectly HBV replication in vitro via activating the immune cells, and could
      contribute to the development of an immunoregulator against HBV infection.

PMID- 16105692
TI  - Genetic fusion of three tandem copies of murine C3d sequences to diphtheria toxin
      fragment B elicits a decreased fragment B-specific antibody response.
AB  - Previous studies have demonstrated that the covalent modification of target
      protein and polysaccharide antigens with the activated complement product C3d
      results in dramatically enhanced immunogenicity of the target antigens. In this
      paper, we describe our attempts to enhance the immunogenicity of the non-toxic B
      fragment of diphtheria toxin (DT-B) by genetic fusion to polypeptides derived
      from the C3d coding sequence. Contrary to expectations, we found that the
      antibody responses elicited by immunizing mice with DT-B genetically linked to
      three tandem copies of C3d-derived sequences were markedly reduced relative to
      the antibody responses elicited by immunizing mice with DT-B alone. These results
      demonstrate levels of complexity in the immunomodulatory effects of the
      complement system that were not apparent in earlier reports on the adjuvant
      effects of C3d administered to mice as genetic fusions to target antigens, such
      as hen egg lysozyme, human immunodeficiency virus (HIV) gp120 or influenza virus
      hemaglutinnin. The data presented herein suggest that C3d may act as a negative
      regulator, in some immunological contexts, for antibody production in the
      mammalian host.

PMID- 16105693
TI  - Inflammatory diseases of the salivary glands in infants and adolescents.
AB  - OBJECTIVE: To determine retrospectively the localization, etiology and treatment
      of inflammatory diseases of the salivary glands in infants and children and to
      evaluate treatment outcome. PATIENTS AND METHODS: Forty-five patients were
      treated in our institution in the period 1966-2000. The patients' records were
      evaluated and the results and side-effects of therapy were documented by a
      controlled follow-up study. RESULTS: Twenty-five of our patients were females
      (55.6%) and 20 males (44.4%). Inflammatory disorders figured most prominently in
      the group of patients between 12 and 16 years (n=14). Inflammation of the
      submandibular glands was the most common disease with 53.3% (n=24). The most
      frequent underlying cause in this subgroup of acute and chronic sialadenitis was
      sialolithiasis of the submandibular gland (40%). All patients were symptom-free
      in the long-term follow-up and all were symptom-free after surgical intervention.
      CONCLUSIONS: The present study shows that diseases of the salivary glands are
      rare among infants and children. Acute and chronic sialadenitis not responding to
      conservative treatment requires an appropriate surgical approach.

PMID- 16105694
TI  - Subglottic stenosis in short-statured children: a case for further investigation
      of airway symptoms in patients with skeletal dysplasias.
AB  - Clinical evaluation of children with skeletal dysplasias is often concentrated on
      morphologic and radiographic assessments, but many of these patients also have
      disease processes of the ear, nose, and throat. We report a case of an 11-month
      old girl with an unknown short-limbed dwarfism, similar to acromicric dysplasia,
      with grade II subglottic stenosis. Laryngotracheoplasty with anterior autologous
      costal cartilage graft and posterior cricoid split was performed at age 13
      months, with subsequent improvement of her airway status. In cases of children
      with skeletal dysplasias and obstructive airway symptoms, formal otolaryngologic
      evaluation is warranted for definitive diagnosis and treatment.

PMID- 16105695
TI  - Amphetamine promotes task-dependent recovery following focal cortical ischaemic
      lesions in the rat.
AB  - This study investigated the effect of amphetamine (AMP) on skilled forelimb use
      following focal cortical ischaemic lesions in the rat. Unilateral lesions were
      produced by a novel method of intracortical microinjection of endothelin-1 (ET
      1), intended to principally target the forelimb representation zone in primary
      motor-primary somatosensory cortex. Lesions were placed in the hemisphere
      contralateral to the preferred limb and produced deficits in skilled forelimb use
      on two tasks: the paw reach (PR) test and the foot fault (FF) test. Beginning on
      post-lesion day (D) 2, animals received injections of 2 mg/kg AMP and were
      injected every third day until D26. Animals were tested both during, and 24 h
      after, AMP administration. AMP facilitated recovery of skilled forelimb use on
      the PR test when assessed during drug-free test sessions. No such effect was seen
      on the FF test. These results demonstrate that sub-acute administration of AMP
      following a unilateral focal ischaemic lesion of FL can facilitate task-dependent
      recovery of skilled forelimb use in the rat. They also demonstrate that different
      behavioural tasks measuring superficially similar behavioural outputs may show
      different sensitivities to such drug effects.

PMID- 16105696
TI  - Effects of housing and nicotine on shuttle-box avoidance in male NMRI mice.
AB  - The present study aimed to evaluate whether housing condition could interact with
      nicotine administration in influencing the acquisition of a two-way active
      avoidance task. Male NMRI mice were either group- or individually housed for 30
      days and, after this period, evaluated both in the actimeter and, 24h later, in
      the elevated plus-maze. On the basis of the percentage of time spent in the open
      arms of the plus-maze, both group- and individually housed mice were sub
      classified into three groups with high, moderate or low anxiety baseline levels.
      Effects of nicotine on the acquisition of the two-way active avoidance task was
      assessed in each of these groups of mice using an automated shuttle-box. Mice
      were treated with nicotine (0.35 mg/kg) or vehicle before each daily training
      session in the shuttle-box (30 trials) over 5 days. The results showed that motor
      activity counts were significantly higher in individually housed mice than in
      group-housed counterparts. The factor "anxiety" in the active avoidance test did
      not reach statistical significance but the factor "housing" did. The number of
      avoidances was higher in individually housed than in group-housed mice. Separate
      analyses performed for individually and group-housed animals indicated that group
      housed nicotine-treated mice displayed fewer number of avoidances than saline
      treated counterparts. It was concluded that housing condition may be a useful
      variable in evaluating the effects of nicotine on learning tasks. Indeed, the two
      way active avoidance task seems to be sensitive to housing condition.

PMID- 16105697
TI  - Age-dependent effects of gestational and lactational iron deficiency on anxiety
      behavior in rats.
AB  - Gestational iron deficiency (ID) has been linked to alterations in GABA
      neurotransmission, but whether these neuronal changes are mirrored in altered
      anxiety behavior in rats is not known. In this experiment, two tests of GABA
      related affective behaviors in rats, ultrasonic vocalizations (USVs) and elevated
      plus maze (EPM) were used to investigate the consequences of maternal ID. Female
      rats were randomly assigned to one of three diet groups: low iron (10-20 ppm Fe),
      recommended (standard) iron control (60 ppm Fe) or lab chow (250 ppm Fe) control.
      Diets started 7 days prior to mating and continued until 10 days after birth
      (PN10). Maternal behavior and offspring growth and activity were also assessed.
      Blood samples taken on PN10 revealed a significant decrement in serum iron and an
      increase in total iron binding capacity in the low iron groups compared to the
      two control groups. Relative to the two control groups, the low iron group
      weighed less on PN1, and this weight difference persisted in adulthood. In
      neonates, the rate of USVs in the low iron group was significantly higher than
      the two control groups, and their general activity was significantly less than
      the controls. Maternal behavior was not significantly different across groups. By
      adulthood, anxiety behavior and motor activity in the low iron group were
      comparable to controls, although the iron deficient subjects habituated more
      slowly. This study shows that prenatal iron deficiency results in increased
      anxiety behavior in neonates that appears to be reversed with iron repletion but
      that some aspects of altered exploratory behavior and growth persist into
      adulthood.

PMID- 16105699
TI  - RNA interference (RNAi) for the silencing of extracellular serine proteases genes
      in Acanthamoeba: molecular analysis and effect on pathogenecity.
AB  - Silencing of extracellular serine protease genes was undertaken by interference
      RNA (RNAi). Chemically synthesized, small interfering RNA (siRNA) were highly
      specific and efficient in silencing the catalytic domain of extracellular serine
      proteases of Acanthamoeba. In order to confirm the silencing phenomenon, the
      extracellular serine protease activities in RNAi-treated parasites were compared
      to non-treated parasites, using zymography profiles, Acanthamoeba-conditioned
      medium (ACM) protease activity, cytotoxicity assays and extracellular serine
      protease mRNA levels analysis. Zymography profiles showed a decrease in the
      extracellular protease levels in the moderate pathogenic and pathogenic strains,
      after treatment with siRNA. These results were supported after the ACM protease
      activity and CPE assays were performed in all studied isolates, showing a lower
      protease activity or cytotoxicity both in the pathogenic and moderate pathogenic
      strains treated with RNAi. These results support that extracellular serine
      proteases are directly involved in the pathogenesis and virulence of
      Acanthamoeba.

PMID- 16105700
TI  - Use of adapted Aspergillus niger in the bioleaching of spent refinery processing
      catalyst.
AB  - Spent refinery processing catalyst is listed as a hazardous waste; the toxicity
      characteristic leaching procedure (TCLP) extracts of the catalyst are found to
      contain heavy metals at concentrations exceeding the regulated levels. In the
      present investigation, Aspergillus niger was adapted to single metal ions Ni, Mo
      or Al (at 100-2,000 mg/L in steps of 100mg/L) and then to a mixture of Ni, Mo and
      Al (at a mass ratio of 1:2:6, as approximately present in the spent catalyst).
      Adaptation experiments with single metals showed that the fungus could tolerate
      up to 1,000 mg/L Ni, 1,200 mg/L Mo and 2,000 mg/L Al. In the presence of a
      mixture of these metals, the fungus was able to tolerate up to 100mg/L Ni,
      200mg/L Mo and 600 mg/L Al. One-step bioleaching experiments with 1 wt% spent
      catalyst (of particle size <37 microm) were carried out using un-adapted and
      various adapted fungal strains. In contrast to the adapted strains, the un
      adapted strain showed no growth in the presence of the catalyst. Ni:Mo:Al-adapted
      strain was the most efficient in the leaching of metals from the catalyst (at
      78.5% Ni, 82.3% Mo and 65.2% Al) over 30 days due to its tolerance to the toxic
      elements at 1 wt%. More importantly, the Ni:Mo:Al-adapted strain was capable of
      bioleaching up to 3 wt% spent catalyst. The TCLP extracts of the spent catalyst
      after bioleaching using the Ni:Mo:Al-adapted strain showed the concentrations of
      Ni and Mo were well within the regulated levels.

PMID- 16105701
TI  - The desaturase from Bacillus subtilis, a promising tool for the selective
      olefination of phospholipids.
AB  - The Delta5-desaturase from Bacillus subtilis has been cloned in Escherichia coli
      BL21 cells and its enzyme activity has been investigated as a function of
      temperature and oxygenation by analyzing methyl ester adducts from the total
      lipid extract in GC-MS measurements. The present data bring out that the activity
      of recombinant Delta5-desaturase, at 20-22 degrees C and 20% oxygen, is
      surprisingly high yielding 22% of C16:1,Delta5 (5-cis-palmitoleic acid) and 13%
      C18:2, Delta5 Delta11 (efedrenic acid). Lower amounts of other mono- and doubly
      Delta5-unsaturated fatty acids were also detected. These findings demonstrate
      that Delta5-desaturase can accept a multiplicity of substrates and is endowed
      with an unprecedented activity among other acyl-lipid desaturases thus
      representing a unique tool for the production of rare Delta5 unsaturated fatty
      acid derivatives.

PMID- 16105698
TI  - Perturbation of chemokine networks by gene deletion alters the reinforcing
      actions of ethanol.
AB  - Microarray analysis of human alcoholic brain and cultured cells exposed to
      ethanol showed significant changes in expression of genes related to immune or
      inflammatory responses, including chemokines and chemokine receptors. To test the
      hypothesis that chemokines exhibit previously undiscovered pleiotropic effects
      important for the behavioral actions of ethanol, we studied mutant mice with
      deletion of the Ccr2, Ccr5, Ccl2 or Ccl3 genes. Deletion of Ccr2, Ccl2 (females)
      or Ccl3 in mice resulted in lower preference for alcohol and consumption of lower
      amounts of alcohol in a two-bottle choice test as compared with wild-type mice.
      Ethanol treatment (2.5 g/kg, i.p.) induced stronger conditioned taste aversion in
      Ccr2, Ccl2 or Ccl3 null mutant mice than in controls. Ccr2 and Ccr5 null mutant
      mice did not differ from wild-type mice in ethanol-induced loss of righting
      reflex (LORR), but mice lacking Ccl2 or Ccl3 showed longer LORR than wild-type
      mice. There were no differences between mutant strains and wild-type mice in
      severity of ethanol-induced withdrawal. Genetic mapping of chromosome 11 for the
      Ccl2 and Ccl3 genes (46.5 and 47.6 cM, respectively) revealed that an alcohol
      induced LORR QTL region was contained within the introgressed region derived from
      129/SvJ, which may cause some behavioral phenotypes observed in the null mice. On
      the contrary, known QTLs on Chr 9 are outside of 129/SvJ region in Ccr2 and Ccr5
      (71.9 and 72.0 cM, respectively) null mutant mice. These data show that
      disruption of the chemokine network interferes with motivational effects of
      alcohol.

PMID- 16105702
TI  - High production of acetone-butanol-ethanol with high cell density culture by cell
      recycling and bleeding.
AB  - A continuous acetone-butanol-ethanol (ABE) production system with high cell
      density obtained by cell-recycling of Clostridium saccharoperbutylacetonicum N1-4
      has been studied. In conventional continuous culture of ABE without cell
      recycling, the cell concentration was below 5.2 g l(-1) and the maximum ABE
      productivity was only 1.85 g l(-1)h(-1) at a dilution rate of 0.20 h(-1). To
      obtain a high cell density at a faster rate, we concentrated the solventogenic
      cells of the broth 10 times by membrane filtration and were able to obtain
      approximately 20 g l(-1) of active cells after only 12h of cultivation.
      Continuous culture with cell-recycling was then started, and the cell
      concentration increased gradually through cultivation to a value greater than 100
      g l(-1). The maximum ABE productivity of 11.0 gl(-1)h(-1) was obtained at a
      dilution rate of 0.85 h(-1). However, a cell concentration greater than 100 gl(
      1) resulted in heavy bubbling and broth outflow, which made it impossible to
      carry out continuous culture. Therefore, to maintain a stable cell concentration,
      cell-bleeding was performed together with cell-recycling. At dilution rates of
      0.11h(-1) and above for cell-bleeding, continuous culture with cell-recycling
      could be operated for more than 200 h without strain degeneration and the overall
      volumetric ABE productivity of 7.55 gl(-1)h(-1) was achieved at an ABE
      concentration of 8.58 gl(-1).

PMID- 16105703
TI  - Expression of the pyranose 2-oxidase from Trametes pubescens in Escherichia coli
      and characterization of the recombinant enzyme.
AB  - cDNA-encoding pyranose 2-oxidase (P2O) from Trametes pubescens was sequenced and
      cloned into Escherichia coli strain BL21/DE3 on a multicopy plasmid under the
      control of trc promoter. The synthesis of P2O was studied in a batch culture in
      M9-based mineral medium: the enzyme was synthesized constitutively at 28 degrees
      C in amount corresponding to 8% of the cell soluble protein (0.6 Umg(-1)). Only
      small portion of P2O (11%) was in the form of non-active inclusion bodies.
      Purified recombinant enzyme has similar physico-chemical and kinetic parameters
      with other P2Os. When compared to the expression of p2o of Trametes ochracea, a
      ratio of the mature enzyme to inclusion bodies found in the same E. coli host at
      28 degrees C is as much as nine times higher. The finding makes the enzyme from
      T. pubescens preferable for the large-scale production by recombinant bacteria.
      The difference in amino acid sequences of the P2O from T. ochracea and T.
      pubescens may explain the favourable trait of the latter enzyme regarding protein
      folding.

PMID- 16105704
TI  - Cigarette smoke concentrate inhibits Kaposi's sarcoma-associated herpesvirus
      infection.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with
      Kaposi's sarcoma (KS), primary effusion lymphoma(PEL), multicentric Castleman
      disease, and other tumors. Progression of KS is dictated by an aberrant
      production of inflammatory cytokines and increase in KSHV infection of cells. In
      this study, we analyzed the effect of cigarette smoke concentrate (CSC) on KSHV
      infection of human foreskin fibroblasts (HFF) using real time quantitative RT
      PCR. Our results demonstrated that the CSC-treated cells supported 50% lower
      infection of KSHV when compared to the untreated cells. Radiolabeled-binding
      assays indicated that CSC inhibited KSHV infection of cells at a post attachment
      stage of entry. Taken together, we report for the first time the ability of CSC
      to specifically inhibit KSHV infection of cells.

PMID- 16105705
TI  - Mechanical horseback riding improves insulin sensitivity in elder diabetic
      patients.
AB  - The present study was undertaken to analyze the acute and chronic effects of
      exercise on insulin sensitivity in elder diabetic patients using a horseback
      riding therapeutic equipment (Joba). The acute effects of exercise were examined
      by means of a single session of Joba riding that lasted for 30 min. The average
      glucose infusion rates (GIR) before and during exercise were regarded as an index
      of the insulin action in peripheral tissues by the euglycemic clamp. The chronic
      effects of exercise were studied by training the elder diabetic patients for 12
      weeks using the Joba apparatus. The insulin sensitivity was determined pre- and
      post-training by a 90 min euglycemic clamp. In the acute study, average GIR
      during exercise was significantly higher than pre-exercise (7.8+/-0.4 versus
      5.2+/-0.3 mg kg(-1)min(-1), P<0.01) and average GIR during recovery decreased to
      almost the same levels of pre-exercise (5.0+/-0.4 mg kg(-1)min(-1); P<0.01). The
      12-week training resulted in a significant increase in the steady-state GIR (from
      5.2+/-0.3 to 7.4+/-0.8 mg kg(-1)min(-1); P<0.05). The steady-state GIR after 12
      weeks of detraining returned to pre-training levels (5.3+/-0.5 mg kg(-1)min(-1);
      P<0.05). In elder diabetic patients, mechanical horseback riding enhances the
      insulin-induced glucose uptake.

PMID- 16105706
TI  - Evaluating program effects on institutional delivery in Peru.
AB  - We evaluate the joint effects of two targeted Peruvian health programs on a
      mother's choice of whether to deliver in a public emergency obstetric care (EmOC)
      facility. The national maternal and child health insurance, or SMI Program,
      provided delivery care coverage to Peru's poorest households beginning in 1998.
      During 1996-2002, Proyecto 2000 sought to improve the quality of EmOC and
      increase utilization of public EmOC facilities in the districts reporting the
      highest maternal and neonatal mortality levels. Our data come from the Proyecto
      2000 endline evaluation, which sampled 5335 mothers living in the catchment areas
      of 29 treatment and 29 matched control EmOC facilities. Using propensity scoring
      and two quality of care indices, we find significantly higher quality of care in
      Proyecto 2000 treatment facilities. Using variance components logistic models, we
      find a mother enrolled in the SMI Program was more likely to have delivered her
      last child in a public EmOC, controlling for household constraints. Residence in
      a Proyecto 2000 treatment area did not significantly affect the choice. A cross
      level interaction term was insignificant, indicating the two program effects were
      independent.

PMID- 16105707
TI  - A Java software for calculating mean breath-by-breath variability in gas exchange
      parameters: application in young cardiac patients with exercise-related periodic
      breathing.
AB  - Oscillatory changes in parameters of gas exchange have been reported during rest
      and exercise in cardiac patients with severely depressed left ventricular
      function. As a result of the growing interest in this oscillatory phenomenon,
      several methods for assessment of this ventilatory response have been presented
      in cardiovascular research. Nowadays, objective measurement becomes more
      important. Therefore, the software reported in this study is based on calculating
      the mean breath-by-breath variability in respiratory variables and has the
      advantage that patients can be compared to normal controls. This Java-based
      software is available for public download under:
      http://www.perswww.kuleuven.ac.be/Steven_Vangesselen

PMID- 16105708
TI  - Deficient cerebral clearance of vasculotropic mutant Dutch/Iowa Double A beta in
      human A betaPP transgenic mice.
AB  - Cerebral amyloid angiopathy (CAA) is a prominent pathological feature of
      Alzheimer's disease and related familial CAA disorders. However, the mechanisms
      that account for the cerebral vascular accumulation of amyloid beta-peptide (A
      beta) have not been defined. Recently, we reported novel transgenic mice (Tg
      SwDI) expressing neuronally derived Swedish/Dutch/Iowa vasculotropic mutant human
      A beta precursor (A betaPP) that develop early-onset and robust accumulation of
      fibrillar cerebral microvascular A beta. Deficient clearance of Dutch/Iowa mutant
      A beta from brain across the capillary blood-brain barrier into the circulation
      may contribute to its potent cerebral accumulation. To further evaluate this
      theory, we generated a new transgenic mouse (Tg-Sw) that is nearly identical to
      Tg-SwDI, except lacking the Dutch/Iowa A beta mutations. Tg-Sw and Tg-SwDI mice
      expressed comparable levels of human A betaPP in brain and not in peripheral
      tissues. However, Tg-SwDI mice strongly accumulated Dutch/Iowa mutant A beta in
      brain, particularly in the cerebral microvasculature, whereas Tg-Sw mice
      exhibited no accumulations of wild-type A beta. Conversely, Tg-SwDI mice had no
      detectable Dutch/Iowa mutant A beta in plasma whereas Tg-Sw mice exhibited
      consistent levels of human wild-type A beta in plasma. Together, these findings
      suggest that while wild-type A beta is readily transported out of brain into
      plasma, Dutch/Iowa mutant A beta is deficient in this clearance process, likely
      contributing to its robust accumulation in the cerebral vasculature.

PMID- 16105709
TI  - Amyloid-beta impairs development of neuronal progenitor cells by oxidative
      mechanisms.
AB  - Neuronal progenitor cells (NPCs) are being considered for treatment of
      neurodegenerative diseases associated with beta-amyloidosis: Alzheimer's disease
      (AD) and Down syndrome (DS). However, the neurotoxic properties of amyloid-beta
      peptide (Abeta) may impair survival and differentiation of transplanted NPCs.
      Hence, we studied the influence of Abeta on development of human NPCs-
      proliferation, migration, formation of colonies of neurons, formation processes-
      in culture. Pre-fibrillized human Abeta1-40 blocked development of neuronal
      colonies. NPC development was impaired in the presence of soluble Abeta1-40 (1.75
      7 microM), and NPC differentiation into large and small neurons was altered, as
      demonstrated by morphometry. Antioxidant vitamin E partially abolished these
      effects, but not the reduced formation of neuronal processes. NPCs cultured with
      7 microM Abeta1-40 accumulated Abeta monomers and oligomers and contained higher
      levels of protein carbonyls and lipid peroxidation products HNE and MDA. We
      suggest that Abeta1-40 impairs development of NPCs by oxidative damage. Hence, a
      prerequisite of successful neuroreplacement therapy using NPCs in AD and DS/AD
      may be removal of amyloid-beta and antioxidative treatment.

PMID- 16105710
TI  - Frequency of IFN-gamma producing cells correlates with adjuvant enhancement of
      bacille Calmette-Guerin induced protection against Mycobacterium bovis.
AB  - Tuberculosis caused by infection with Mycobacterium tuberculosis or Mycobacterium
      bovis remains one of the most important infectious diseases of man and animals.
      The current vaccine M. bovis Calmette-Guerin (BCG) demonstrates variable efficacy
      and so a more robust strategy to either replace, or more likely supplement it, is
      required. Prime-boost strategies where immunity induced by BCG is boosted by a
      second heterologous vaccine represent a promising avenue of research. We have
      evaluated the ability of a protein subunit vaccine using the antigen Rv3019c to
      either prime or boost immunity induced by BCG in a murine M. bovis challenge
      model. Despite the induction of anamnestic T cell responses, we report that
      antigen-independent immune stimulation with adjuvant in conjunction with BCG
      could enhance the level of protection induced by BCG alone. Importantly this
      improved protection correlated with pre-infection frequencies of ex vivo IFN
      gamma producing cells in the spleen, providing a possible surrogate correlate of
      protection for future vaccination studies.

PMID- 16105711
TI  - Multivalent liposome-based vaccines containing different serosubtypes of PorA
      protein induce cross-protective bactericidal immune responses against Neisseria
      meningitidis.
AB  - Four serosubtypes (P1.7, 16, P1.7-2, 4, P1.19, 15 and P1.5-1, 10-4) of the PorA
      outer-membrane protein of Neisseria meningitidis were purified as recombinant
      proteins and incorporated into liposomes to investigate their immunogenicity.
      Each serosubtype induced high levels of bactericidal activity against the
      homologous strain. In addition, liposome preparations containing multiple
      serosubtypes induced high levels of bactericidal activity against each of the
      four strains. Significantly, antisera raised against monovalent and multivalent
      liposomes also showed cross-reactive bactericidal activity against heterologous
      strains. These data demonstrate that multivalent liposome vaccines, containing
      multiple PorA serosubtypes, have the potential to provide protection against a
      broad range of meningococcal strains.

PMID- 16105712
TI  - Head and neck cancer: to what extent can psychological factors explain
      differences between health-related quality of life and individual quality of
      life?
AB  - AIMS: To assess the extent to which individualised quality of life (QoL) was
      related to standardised health-related quality of life (HR-QoL), and to assess
      how much of the variation in each of these measures could be explained by
      psychological variables. METHODS: Fifty-five patients with newly diagnosed head
      and neck cancer completed the following outcome measures: the Patient Generated
      Index (PGI), the European Organisation for Research and Treatment of Cancer
      (EORTC) QLQ-C30 and the Short Form 12 version 2 (SF-12v2). Explanatory factors
      were measured with the following: the Illness Perceptions Questionnaire-Revised
      (IPQ-R), the Beliefs about Medicines Questionnaire (BMQ), the Hospital Anxiety
      and Depression Scale (HADS), and the Brief COPE (a shortened version of the
      COPE). MAIN FINDINGS: Standardised and individualised QoL measures were
      correlated only partly. The PGI correlated only with EORTC QLQ-C30 domains of
      emotional and cognitive functioning and SF-12 domains of mental health, emotional
      role, social, and physical role. The underlying psychological factors explaining
      each of the three outcome measures were different. CONCLUSIONS: Respondent
      generated measures such as the PGI could be used as an adjunct to more
      standardised measures of HR-QoL clinically. This has implications for assessing
      the impact of head and neck cancer on individualised QoL and also for improving
      patients' outcome through interventions aimed at targeting underlying
      psychological factors.

PMID- 16105713
TI  - The correlation between indices of deprivation and health-related quality of life
      in patients with oral and oropharyngeal squamous cell carcinoma.
AB  - Deprivation influences the incidence and outcome of patients with cancer. Health
      related quality of life (HR-QoL) is an important measure of outcome but there is
      little on this subject and its correlation with deprivation in patients with oral
      and oropharyngeal cancer. Our aim was to ascertain the extent of deprivation in a
      cohort of patients who had operations for primary oral and oropharyngeal cancer
      and how deprivation affected HR-QoL in these patients during and after their
      treatment. A total of 278 consecutive patients who were operated on for oral and
      oropharyngeal cancer were included in this study. Validated measures of
      deprivation scores (Townsend, Carstairs, Jarman and Index of Multiple Deprivation
      2000) were calculated, as well as patient-based indicators of social
      circumstances (marital status, smoking habit, alcohol intake). Comparison was
      made with the University of Washington-Quality of Life (UW-QoL) scores before and
      after treatment (6, 12, and 24 months).

PMID- 16105714
TI  - Closed rupture of the thumb flexor tendon pulleys.
AB  - Closed flexor tendon pulley ruptures are relatively rare injuries. All previously
      reported cases have been in the long finger pulleys. To our knowledge, there has
      not been a case of closed thumb flexor tendon pulley rupture reported in the
      literature. This paper presents two cases of this pathology and discusses
      appropriate treatment of it.

PMID- 16105715
TI  - Avoidance bio-assays may help to test the ecological significance of soil
      pollution.
AB  - We measured the short-term (100 min) avoidance of a soil heavily polluted by
      hydrocarbons by the soil springtail Folsomia candida, at six rates of dilution in
      a control, unpolluted soil. We compared the results with those of long-term (40
      day) population tests. Five strains were compared, of varying geographical and
      ecological origin. When pure, the polluted soil was lethal in the long-term and
      avoided in the short-term by all strains. Avoidance tests, but not population
      tests, were able to discriminate between strains. Avoidance thresholds differed
      among strains. Two ecological consequences of the results were discussed: (i)
      toxic compounds may kill soil animals or deprive them from food, resulting in
      death of populations, (ii) pollution spots can be locally deprived of fauna
      because of escape movements of soil animals. Advantages and limitations of the
      method have been listed, together with proposals for their wider use in soil
      ecology and ecotoxicology.

PMID- 16105716
TI  - Effect of copper on the adsorption of p-nitrophenol onto soils.
AB  - The effect of copper on adsorption of p-nitrophenol on two typical Chinese soils
      was investigated using a batch-equilibration method. Adsorption experiments were
      carried out when both copper and p-nitrophenol were adsorbed simultaneously, and
      when copper was previously adsorbed on soils. It was observed that adsorption of
      p-nitrophenol decreased with increasing copper concentrations thereby indicating
      a competition between copper and p-nitrophenol for occupying the adsorption sites
      on soils. Moisture increased the hydrated sphere and the acidity of water
      surrounding the cation, which further reduced the adsorption of p-nitrophenol.
      Fourier transform infrared spectroscopy study provided the direct evidence for
      the coordination of p-nitrophenol sorbed by soils with metal cation in n-hexane
      system. It was observed that the perturbations included a red shift of the
      nu(asym) (NO) band, a concomitant blue-shift of the nu(sym) (NO) band and a blue
      shift of C-N band when compared with the infrared spectra obtained from water
      solution.

PMID- 16105717
TI  - Prefrontal substrates of empathy: psychometric evidence in a community sample.
AB  - Empathy is a vicarious experience of others' emotions, and is crucial to many
      forms of adaptive social interaction. Clinical, experimental, and functional
      neuroimaging studies convergently suggest a role for prefrontal-limbic circuits
      in mediating empathy. This study examined the prefrontal basis of empathy in a
      community sample using self-report measures: the frontal systems behavior scale
      (FrSBe), Barratt impulsiveness scale (BIS), and the interpersonal reactivity
      index (IRI). Multiple correlations emerged supporting an inverse relationship
      between prefrontal system dysfunction and empathy, particularly emotional empathy
      and perspective taking. Many of these relationships persisted after controlling
      for age, sex, and education. However, FrSBe scales did not correlate with one's
      identification with fictional characters, and motor impulsivity correlated
      positively, presumably due to the different cognitive and emotional context (i.e.
      real versus fictional individuals). These studies parallel others using objective
      methodologies and suggest a graded relationship between prefrontal function and
      empathy and likely reflect normal variations in prefrontal-limbic function.

PMID- 16105718
TI  - Cholecystokinin-8 increases Fos-like immunoreactivity in myenteric neurons of the
      duodenum and jejunum more after intraperitoneal than after intravenous injection.
AB  - The objective of this study was to measure the relative efficacy and potency of
      cholecystokinin-8 (CCK-8) given by intraperitoneal (i.p.) and intravenous (i.v.)
      injection to stimulate Fos-like immunoreactivity (Fos-LI) in neurons of the
      myenteric plexus in the duodenum and jejunum. The subjects for his experiment
      were 40 male Sprague-Dawley rats divided into eight treatment groups (n=5 rats
      per treatment). Four groups of rats were injected with 5, 10, and 40 microg/kg
      sulfated CCK-8 and saline (control) i.p., and the remaining groups with the same
      treatments i.v. We then detected Fos-LI, a marker for neuronal activation, in the
      myenteric plexus of the duodenum and jejunum, in response to the previous doses
      and routes. All of the CCK-8 doses administered by both routes increased Fos-LI
      in the myenteric plexus of the duodenum and jejunum significantly more than
      saline did. Although both routes were efficacious in increasing Fos-LI, CCK-8
      i.p. was significantly more potent than CCK-8 i.v. These data provide
      immunohistochemical evidence that i.p. administration of CCK-8 is a more potent
      stimulant of Fos-LI in the neurons of the myenteric plexus of the duodenum and
      jejunum than i.v. injection.

PMID- 16105719
TI  - Natural infection by Giardia sp. and Cryptosporidium sp. in dairy goats,
      associated with possible risk factors of the studied properties.
AB  - Visits were made to six farms raising dairy goats located in the mountain region
      of the state of Rio de Janeiro, Brazil, seeking to identify parasitism by Giardia
      sp. and Cryptosporidium sp. During the visits, fecal samples were collected from
      approximately 10% of the stock of each property. A questionnaire was given to the
      keepers on each property to obtain data for epidemiological analysis. A total of
      105 fecal samples was collected, 56 from adult animals (over 12 months of age)
      and 49 from juvenile animals (less than 12 months). The fecal material was
      processed and subjected to the centrifuge-flotation technique and to staining
      with safranine-methylene blue. Protozoans of the genus Cryptosporidium were found
      at two properties, where the hygiene conditions of the installations were
      considered average and the stalls were made of wood slats raised from the ground.
      A total of five (4.8%) of the samples was found to be positive for the presence
      of this protozoan, all from juvenile animals. Cysts of the genus Giardia were
      found at two properties. Of the 105 samples analyzed, the protozoan was detected
      in 15 (14.3%), all in juvenile animals, and animals in the age range of 1-3
      months had significantly more infections. Age, sanitary condition of the stalls
      and stalls made of wood slats and raised from the ground, can be pointed out as
      possible risk factors for infection by Giardia sp. and Cryptosporidium sp. The
      study reports for the first time the occurrence of Cryptosporidium sp. and
      Giardia sp. in goats in the state of Rio de Janeiro.

PMID- 16105720
TI  - The relationship between responsiveness against gastrointestinal nematodes in
      lambs and the numbers of circulating IgE-bearing cells.
AB  - The objective of this study was to determine if any relationship exists between
      responsiveness against gastrointestinal nematodes (GI) in lambs and circulating
      IgE-bearing cells. Scottish Blackface lambs that were grazing on pasture infected
      with Teladorsagia circumcincta (T. circumcincta) were ranked in order of their
      cumulative resistance to nematode infection as determined by their faecal egg
      counts (FECs) from material taken throughout the grazing season. The 10 lambs
      that had the lowest egg count rankings termed "responders" and the 10 lambs that
      had the highest egg count rankings termed "non-responders", were selected using
      data from the whole season or the middle or end of the grazing season. The number
      of circulating IgE-bearing cells present in the selected responder and non
      responder lambs was investigated. The study was followed for two grazing seasons.
      Results showed that there were higher numbers of circulating IgE-bearing cells in
      the blood of responder lambs when compared to non-responders in the lambs
      selected from the middle of the season during both grazing seasons. A significant
      difference in the number of these IgE-bearing cells in responder and non
      responder lambs was also demonstrated at the last two time points (p<0.05) of the
      initial grazing season. FACS analysis confirmed that IgE-bearing cells were found
      predominantly among lymphocytes/monocytes. The present study provides further
      evidence for an active role for IgE antibody in nematode immunity, and suggests
      that these circulating IgE-bearing cells might serve as additional markers for
      selecting animals that are responsive against T. circumcincta infections in
      lambs.

PMID- 16105721
TI  - Genetic and biologic characteristics of Toxoplasma gondii isolates in free-range
      chickens from Colombia, South America.
AB  - The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator
      of the prevalence of T. gondii oocysts in the soil because chickens feed from the
      ground. The prevalence of T. gondii in 77 free-range chickens (Gallus domesticus)
      from Colombia, South America was determined. Antibodies to T. gondii were assayed
      by the modified agglutination test (MAT), and found in 32 (44.4%) of 72 chickens
      with titers of 1:5 in 4, 1:10 in 3, 1:20 in 1, 1:40 in 1, 1:80 in 8, 1:160 in 8,
      1:320 in 3, and 1:640 or higher in 4. Hearts and brains of 31 seropositive
      chickens were pooled and bioassayed in mice. Tissues from 32 (16+16) seronegative
      chickens were pooled and fed to two, T. gondii-free cats, and tissues from nine
      chickens without matching sera were fed to one T. gondii-free cat. Feces of cats
      were examined for oocysts. T. gondii oocysts were excreted by a cat that was fed
      tissues of 16 seronegative chickens. T. gondii was isolated by bioassay in mice
      from 23 chickens with MAT titers of 1:20 or higher. All infected mice from 16 of
      the 23 isolates died of toxoplasmosis. Overall, 82 (81.1%) of 101 mice that
      became infected after inoculation with chicken tissues died of toxoplasmosis.
      Genotyping of these 24 isolates using polymorphisms at the SAG2 locus indicated
      that seven T. gondii isolates were Type I, 17 were Type III, and none was Type
      II. Phenotypically, T. gondii isolates from chickens from Colombia were similar
      to isolates from Brazil but different from the isolates from North America; most
      isolates from chickens from Brazil and Colombia were lethal for mice whereas
      isolates from North America did not kill inoculated mice. Genetically, none of
      the T. gondii isolates from Colombia and Brazil was SAG2 Type II, whereas most
      isolates from chickens from North America were Type II. This is the first report
      of genetic characterization of T. gondii isolates from Colombia, South America.

PMID- 16105722
TI  - Genotyping of porcine circovirus type 2 from a variety of clinical conditions in
      China.
AB  - Genotypes of porcine circovirus type 2 (PCV2) in clinical tissue specimens
      collected from pigs of different region in China between 2001 and 2003 were
      analyzed by PCR and restriction fragment length polymorphism (RFLP) analysis of
      PCV2 genomic DNA encompassing the complete ORF2. The results showed that nine
      different genotypes (A-I) were identified and designated CHN-2A, CHN-2B, CHN-2C,
      CHN-2D, CHN-2E, CHN-2F, CHN-2G, CHN-2H and CHN-2I, respectively. Amongst the
      genotypes, 0.6% were CHN-2A (1/173), CHN-2B (1/173) and CHN-2C (1/173) RFLP
      profile; 2.3% were CHN-2F (4/173) and CHN-2G (4/173); 5.8% were CHN-2D (10/173);
      8.6% were CHN-2E (15/173); 18.5% were CHN-2I (32/173) and 60.7% were CHN-2H
      (105/173). Therefore, our results suggest that CHN-2H is the dominant genotype of
      PCV2 prevailing in China. Sequence analysis revealed that ORF2 genes of different
      genotypic PCV2 exhibited the variation extent of 90.5-99.5% and 88-100% in
      nucleotide and amino acid respectively. The deduced amino acid sequences
      alignment of the capsid protein encoded by ORF2 of PCV2 presented that three
      major regions with greater heterogeneity existed at residues 57-90, 121-136 and
      180-191 among nine genotypic PCV2. It was concluded that there exist variation in
      ORF2 genes of different genotypic PCV2 prevailing in China.

PMID- 16105723
TI  - Solid state characteristics of ternary solid dispersions composed of PVP VA64,
      Myrj 52 and itraconazole.
AB  - The purpose of the present study was to characterize the solid state properties
      of ternary solid dispersions made up of PVP VA64, Myrj 52 and itraconazole. The
      solid dispersions were prepared by dissolving the materials in methylene
      chloride, followed by evaporation under reduced pressure of the solvent at 55
      degrees C in a rotovapor. Binary and ternary solid dispersions were characterized
      by standard and modulated temperature differential scanning calorimetry and X-ray
      powder diffraction. Although PVP VA64 and itraconazole were found to be
      completely miscible in the solid state, addition of a small amount of Myrj 52 to
      the drug-polymer system leads to separation of itraconazole thus demonstrating
      that Myrj 52 expels the drug from the polymer phase.

PMID- 16105724
TI  - Transport of hydroxyzine and triprolidine across bovine olfactory mucosa: role of
      passive diffusion in the direct nose-to-brain uptake of small molecules.
AB  - Hydroxyzine and triprolidine have both been reported to reach the CNS following
      nasal administration. The objective of this study was to investigate their in
      vitro permeation across bovine olfactory mucosa in order to further characterize
      the biological and physicochemical parameters that influence direct nose-to-brain
      transport. In vitro experiments were conducted using Sweetana-Grass (Navicyte)
      vertical diffusion cells to evaluate the effect of directionality, donor
      concentration and pH on the permeation of hydroxyzine and triprolidine across
      excised bovine olfactory mucosa. These studies demonstrated that the Jm-s
      (mucosal-submucosal flux) and Js-m (submucosal-mucosal flux) of hydroxyzine and
      triprolidine across the olfactory mucosa were linearly dependent upon the donor
      concentration without any evidence of saturable transport. Hydroxyzine inhibited
      the efflux of P-gp substrates like etoposide and chlorpheniramine across the
      olfactory mucosa. Both hydroxyzine and triprolidine reduced the net flux (Js-m-Jm
      s) of etoposide with IC50 values of 39.2 and 130.6 microM, respectively. The
      lipophilicty of these compounds, coupled with their ability to inhibit P-gp,
      enable them to freely permeate across the olfactory mucosa. Despite the presence
      of a number of protective barriers such as efflux transporters and metabolizing
      enzymes in the olfactory system, lipophilic compounds such as hydroxyzine and
      triprolidine can access the CNS primarily by passive diffusion when administered
      via the nasal cavity.

PMID- 16105725
TI  - The problem of single parent/child paternity analysis--practical results
      involving 336 children and 348 unrelated men.
AB  - In a certain amount of paternity investigations, only DNA from child and alleged
      father is analyzed, thus increasing the possibility of false paternity
      inclusions. The aim of this study was to determine how many wrong paternity
      inclusions could be detected in a rather small geographical area comparing
      empirical results from 336 children and 348 men (13-15 STRs were investigated per
      person). This comparison between each child and all unrelated men (i.e. all
      putative fathers from the other cases) with an especially designed computer
      program resulted in 116,004 man/child pairs. Less than three excluding STRs were
      found in 1666 child/unrelated man pairs (1.44% of the comparisons). At least one
      unrelated man with only two or less STR mismatches could be determined for 322
      children (95.8% of all investigated children). In 26 comparisons no STR
      mismatches between a child and an unrelated man were detected, thus at least one
      and up to three "second father(s)" under 350 men could be found for 23 children,
      if the mother is excluded. Paternity probabilities between 95.475% and 99.996%
      were calculated. Our results underline the difficulties in motherless paternity
      cases using only STR analysis and advise great precaution in assigning verbal
      predicates such as "paternity proven" in those investigations.

PMID- 16105726
TI  - Dietary galactose inhibits GDF-9 mediated follicular development in the rat
      ovary.
AB  - Clinical evidence suggests an association between galactosemia and premature
      ovarian failure, but the mechanism is still not fully understood. Growth
      differentiation factor-9 (GDF-9) is thought to be an obligatory growth factor
      during the gonadotropin-independent phase of folliculogenesis. The objective of
      this study was to examine the effects of galactose on initiation of
      folliculogenesis in the peripubertal interval and the connection between
      galactose toxicity and GDF-9 expression in the ovary. After immature Long-Evans
      rats (n = 10) were fed a diet consisting of 20% galactose for 19 days, whole
      body, ovary and uterine weights were measured. Serum estradiol and progesterone
      concentrations were measured by radioimmunoassay. Ovarian follicles were counted
      by morphometric analysis and GDF-9 expression was investigated by
      immunohistochemistry and immunoblot assay. Galactose treatment did not affect the
      onset of puberty as marked by the time of vaginal opening. The galactose diet
      significantly decreased the number of healthy growing follicles. The results of
      immunoblot assay showed that both bands corresponding to propeptide and mature
      forms of GDF-9 decreased with the galactose diet about 90 and 70%, respectively.
      The results of immunohistochemical staining showed that the GDF-9 positive
      follicle number and the ratio of GDF-9 positive to GDF negative (primordial/non
      growing) follicles significantly decreased with this high galactose diet. The
      present study suggests that a high galactose diet inhibits follicular
      development, possibly through down-regulation of GDF-9 in the rat ovary, implying
      that GDF-9 may be involved in galactose-related ovarian toxicity.

PMID- 16105727
TI  - Complications associated with segmentation of the maxilla: a retrospective
      radiographic follow up of 82 patients.
AB  - The aim of the present study was to retrospectively examine the clinical and
      radiographic incidence and frequency of injuries to teeth and their surrounding
      tissues adjacent to interdental osteotomies in conjunction with segmentation of
      the maxilla. Vertical interdental osteotomies have been performed in combination
      with Le Fort I osteotomy for correction of various dento-facial deformities. All
      our orthognathic patients are followed prospectively in a standardized manner.
      Eighty-two consecutive patients who underwent dento-facial correction by
      segmented maxillary osteotomy alone or in combination with simultaneous
      mandibular surgery between 1992 and 1998 were included in the study. They were
      followed for up to 30 months postoperatively. A total of 158 interdental
      osteotomies were performed, involving a total of 316 teeth. Only a small number
      of complications such as osteolytic processes, marginal bone destruction, root
      resorption or mechanical injuries to the teeth were seen.

PMID- 16105728
TI  - Lack of association between variations in the brain-derived neurotrophic factor
      (BDNF) gene and temporal lobe epilepsy.
AB  - Recently, an association between the C240T polymorphism in the brain-derived
      neurotrophic factor (BDNF) gene and partial epilepsy was demonstrated in a
      Japanese population. In this study we attempted to replicate the initial finding
      in a patient-control population of European ancestry and in addition tested
      whether the functional Val66Met polymorphism is associated with temporal lobe
      epilepsy (TLE). Genotypes of 151 TLE patients and 189 controls did not differ
      significantly for either of the variations. Results suggest that neither of the
      studied polymorphisms are strong susceptibility factors for TLE in this sample of
      individuals of European ancestry.

PMID- 16105729
TI  - Caspofungin treatment failure in a patient with invasive candidiasis and
      concomitant rifampicin treatment.

PMID- 16105730
TI  - Reorganization of lipid nanocapsules at air-water interface 3. Action of
      hydrolytic enzymes HLL and pancreatic PLA2.
AB  - The action of the hydrolytic enzymes humicola lanuginosa lipase (HLL) and
      pancreatic phospholipase A2 (PLA2) on monolayers formed from lipid nanocapsules
      (LNC) and model monolayers containing their components, Labrafac, Solutol and
      Lipoid, is studied by simultaneous measuring the changes in the film area and the
      surface potential in the "zero order" trough at constant surface pressure (pi).
      The kinetic models describing the hydrolysis by HLL of the Labrafac, Solutol and
      their mixtures have been proposed. By using the developed theoretical approach
      together with the experimental results the surface concentrations of the
      substrates, hydrolysis products and values of the global kinetic constants were
      obtained. The comparison between the global kinetic constants in the case of HLL
      hydrolysis of pure Labrafac, Solutol monolayers and those of the model mixed
      Labrafac/Solutol monolayers, shows that the rates of hydrolysis are of the same
      order of magnitude, i.e. an additively of the HLL enzyme action is observed. The
      composition of the mixed Labrafac/Solutol monolayer, formed after the interfacial
      LNC destabilization, was estimated.

PMID- 16105731
TI  - Inhaled corticosteroids and survival in COPD patients receiving long-term home
      oxygen therapy.
AB  - BACKGROUND: Several observational studies suggest that therapy with inhaled
      corticosteroids (ICS) is associated with reduced mortality in patients with
      chronic obstructive pulmonary disease (COPD). However, none of these has reported
      survival data in COPD patients with respiratory insufficiency who require
      domiciliary oxygen therapy. The present study was conducted to examine the
      association between ICS and all-cause mortality in patients with severe COPD and
      chronic hypoxemia. PATIENTS AND METHODS: From a tertiary referral clinic, we
      identified 145 consecutive COPD patients who met the criteria for long-term
      oxygen therapy between 1996 and 2002. We compared the hazard ratio (HR) for all
      cause mortality over 1 year between patients who were (n=55) and were not treated
      with ICS (n=90). RESULTS: In a crude analysis, the use of ICS was associated with
      a HR of 0.38 (95% confidence interval (CI)=0.18-0.79). After adjustments for age,
      sex, use of oral steroids, and beta2-agonists, PaO2 and PaCO2, the HR was 0.46
      (95% CI=0.21-0.98). CONCLUSIONS: Our findings indicate that ICS may reduce all
      cause mortality in patients with severe COPD and chronic hypoxemia, who require
      long-term domiciliary oxygen therapy. These data suggest that ICS may play an
      important role in improving clinical outcomes in patients with advanced COPD.

PMID- 16105732
TI  - Anatomy of a successful imprint: analysing the recognition mechanisms of a
      molecularly imprinted polymer for quercetin.
AB  - This study comprises a retrospective analysis of a successful molecular imprint
      for quercetin with the main aim of deriving rational design strategies for more
      effective molecularly imprinted polymers. Hence, polymers of varying composition
      were synthesised and chromatographically characterised to examine the effects of
      monomer-template ratios. (1)H NMR analysis of the pre-polymerisation mixture
      yielded further information on the nature of the complexes formed prior to the
      polymerisation step. A direct correlation between the optimum monomer-template
      ratio derived from the chromatographic studies and the monomer-template ratio
      providing the most stable pre-polymerisation complexes observed via (1)H NMR T(1)
      relaxation time measurements, suggests that the formation of particularly stable
      pre-polymerisation complexes is responsible for an increased formation of
      selective binding sites during the polymerisation step. Furthermore, physical
      aspects of the polymerisation, such as the MIP surface area and macroscopic phase
      partitioning of the mixture during the polymerisation are investigated. The
      observed effects and their analytical assessment offer insight into the
      mechanisms governing MIP selectivity at a molecular level.

PMID- 16105733
TI  - Indole-5-phenylcarbamate derivatives as human non-pancreatic secretory
      phospholipase A2 inhibitor.
AB  - The synthesis of the human non-pancreatic secretory phospholipase A2 inhibitor
      (IC(50)=1.81+/-0.59 microM) is reported.

PMID- 16105734
TI  - Optimization of piperazinebenzylamines with a N-(1-methoxy-2-propyl) side chain
      as potent and selective antagonists of the human melanocortin-4 receptor.
AB  - Piperazinebenzylamines bearing a small N-(1-methoxy-2-propyl) side chain were
      found to be potent and selective antagonists of the human melanocortin-4 (MC4)
      receptor. Compound 7b, having K(i) values of 6.9 and 2800 nM at the human MC4 and
      MC3 receptors, respectively, has moderate oral bioavailability in mice, which is
      improved relative to the arylethyl analogues.

PMID- 16105735
TI  - Anthraquinone derivatives as a new family of protein photocleavers.
AB  - Certain anthraquinones, which are present in many biologically important natural
      products, effectively and randomly cleaved proteins (BSA or Lyso) during
      photoirradiation using a long wavelength UV light without any further additives.
      It was also found that this ability could be improved by the attachment of a
      suitable substituent into the anthraquinone core skeleton.

PMID- 16105736
TI  - Synthesis and antibacterial activity of N-(5-benzylthio-1,3,4-thiadiazol-2-yl)
      and N-(5-benzylsulfonyl-1,3,4-thiadiazol-2-yl)piperazinyl quinolone derivatives.
AB  - A series of N-(5-benzylthio-1,3,4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1,3,4
      thiadiazol-2-yl) derivatives of piperazinyl quinolones was synthesized and
      evaluated for antibacterial activity against Gram-positive and Gram-negative
      microorganisms. Some of these derivatives exhibit high activity against Gram
      positive bacteria; Staphylococcus aureus and Staphylococcus epidermidis,
      comparable or more potent than their parent N-piperazinyl quinolones norfloxacin
      and ciprofloxacin as reference drugs. The SAR of this series indicates that both
      the structure of the benzyl unit and the S or SO(2) linker dramatically impact
      antibacterial activity.

PMID- 16105737
TI  - New orally active spiro 1,2,4-trioxanes with high antimalarial potency.
AB  - A new series of functionalized 1,2,4-trioxanes 10-21 have been prepared and
      assessed for antimalarial activity in mice. Several of these trioxanes show
      significant activity. Trioxane 16, the most active compound of the series, has
      shown activity by oral route which is comparable with that of the clinically used
      drug, beta-arteether.

PMID- 16105738
TI  - Potent and selective MC-4 receptor agonists based on a novel disulfide scaffold.
AB  - Extensive structure-activity relationship studies utilizing a beta-MSH-derived
      cyclic nonapeptide, Ac-Tyr-Arg-[Cys-Glu-His-D-Phe-Arg-Trp-Cys]-NH(2) (3), led to
      identification of a series of novel MC-4R selective disulfide-constrained
      hexapeptide analogs including Ac-[hCys-His-D-Phe-Arg-Trp-Cys]-NH(2) (12). The
      structural modifications associated with profound influence on MC-4R potency and
      selectivity were ring size, ring conformation, and the aromatic substitution of
      the D-Phe7. These cyclic peptide analogs provide novel and enhanced reagents for
      use in the elucidation of melanocortin-4 receptor-related physiology, and may
      additionally find application in the treatment of obesity and related metabolic
      disorders.

PMID- 16105739
TI  - A synthetic approach to the generation of quercetin sulfates and the detection of
      quercetin 3'-O-sulfate as a urinary metabolite in the rat.
AB  - To study the biological effects of quercetin, authentic products of quercetin
      metabolism are required as standards. The synthesis of quercetin sulfate
      standards is thus described. Quercetin was reacted with a 10-fold molar excess of
      sulfur trioxide-N-triethylamine, and the products were analyzed by HPLC and mass
      spectrometry. Four monosulfates and three disulfates were identified, and
      structural inferences were drawn by 1H NMR spectrometry of HPLC peak isolates.
      Analysis of the urine of rats that had received quercetin (1.9 g/kg po) yielded a
      single peak, which by comparison with the products of the reaction between
      quercetin and sulfur trioxide-N-triethylamine was identified as quercetin 3'-O
      sulfate.

PMID- 16105740
TI  - Weak energy dependence of EBT gafchromic film dose response in the 50 kVp-10 MVp
      X-ray range.
AB  - The energy dependence of the dose response of EBT Gafchromic film is assessed
      over a broad energy range, from superficial to megavoltage X-rays. The film is
      auto-developing and sensitive, it provides accurate dose assessment of low doses
      (about 1-2 Gy) used in radiotherapy. The energy dependence of the response of EBT
      film was found to be very weak: the variations do not exceed 10% over the range
      from 50 kVp to 10 MVp X-rays. By contrast, variations of the response of
      Gafchromic HS film are as big as 30% over the same range, and variations of the
      response of Radiographic film exceed one order of magnitude. This weak dependence
      provides significantly higher accuracy of dose measurements under conditions of
      varying spectral quality of X-ray beams, which are common in radiation therapy.

PMID- 16105741
TI  - Inhibitory effects of interferon-gamma on myocardial hypertrophy.
AB  - Prostaglandin F(2alpha) (PGF(2alpha)) plays an important role in pathologic
      cardiac growth. After testing several immune cytokines, we found that interferon
      gamma (IFN-gamma) inhibited responsiveness of adult myocytes to PGF(2alpha). The
      present study was designed to test the hypothesis that IFN-gamma inhibits cardiac
      hypertrophy induced by PGF(2alpha). Incubation of cultured adult rat cardiac
      myocytes with PGF(2alpha) caused cell spreading, which was inhibited by IFN
      gamma. The inhibitory effect was not affected by nitric oxide (NO) synthase
      inhibitors. In addition, administration of fluprostenol, a more selective agonist
      at the PGF(2alpha) receptor, induced cardiac hypertrophy in rats. Chronic
      treatment with IFN-gamma inhibited this myocardial growth, and the inhibitory
      effect of IFN-gamma was not accompanied by an increase in myocardial NO synthase
      gene expression. Further, abdominal aortic constriction resulted in a substantial
      increase in heart, ventricular and left ventricular weights to BW ratio that was
      significantly attenuated by treatment with IFN-gamma. The results demonstrate
      that IFN-gamma inhibits the in vitro and in vivo effects of PGF(2alpha) on
      cardiac hypertrophy, and that the mechanism of action is likely independent of NO
      production. IFN-gamma also attenuated cardiac hypertrophy induced by pressure
      overload, suggesting that PGF(2alpha) plays a role in the pathogeneses of this
      severe type of cardiac hypertrophy.

PMID- 16105742
TI  - MCP-1-stimulated chemotaxis of monocytic and endothelial cells is dependent on
      activation of different signaling cascades.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is important in attracting monocytes
      to sites of inflammation. Besides induction of monocyte recruitment, MCP-1 can
      also affect chemotactic response of endothelial cells. The molecular mechanisms
      involved in MCP-1-induced cell migration are poorly understood. In the current
      investigation, we demonstrate activation of p42/44(ERK1/2) and p38 mitogen
      activated protein kinases (MAPKs), phosphatydilinositol-3-kinase (PI3K) and Src
      kinases in both monocytes and endothelial cells stimulated with MCP-1 in vitro.
      The response was rapid and time-dependent, detectable within 3 min of MCP-1
      stimulation. MCP-1-induced phosphorylation of p42/44(ERK1/2) MAPKs was partially
      blocked by inhibitor of PI3K LY294002, while phosphorylation of p38 MAPK was
      diminished to a greater extent in presence of Src-kinase inhibitor PP2. There was
      a substantial inhibition of monocyte migration upon treatment with inhibitors of
      p38 MAPK, at the same time inhibition of p42/44(ERK1/2) MAPK activation had no
      effect. On the contrary, the MCP-1-stimulated chemotaxis of endothelial cells was
      completely abolished by inhibitors of PI3K and p42/44(ERK1/2), but not by p38
      MAPK inhibitors. These results suggest that parallel signal transduction pathways
      are activated by MCP-1, and that depending on the cell type these pathways
      differentially contribute to cell chemotactic activity.

PMID- 16105743
TI  - Ultrastructural characterization of whole hydrosalpinx from infertile Chinese
      women.
AB  - Hydrosalpinx (HSP) has been shown to be detrimental to the outcome of assisted
      reproduction, but little is known of its pathology. This prospective study
      examined and detailed ultrastructural characterization of HSP of infertile women
      presenting for assisted reproductive treatments. Both light and electron
      microscopies were used to characterize HSP. Hematoxylin and eosin staining of HSP
      showed areas without epithelial cell lining or with abnormalities such as
      flattening of the epithelial layer and exfoliation of epithelial cells with
      occasional normal columnar epithelial lining. HSP muscle fibers were atrophic and
      occasionally replaced by fibrous tissues, or separated by areas of severe edema.
      Inflammatory cells could be found in hydrosalpinx fluid (HF) in the lumen in
      areas with flattened to no epithelial cells, without epithelial lining, as well
      as in dilated blood vessels and/or lymph vessels. Scanning electron microscopy of
      the epithelial surface revealed epithelial denudation-severe loss of both cilia
      and microvilli and stomata exuding globular bodies on eroded ampulla surfaces.
      Severe chronic inflammation and damage to the epithelial lining and musculature
      of Fallopian tubes and the presence of inflammatory cells provides an explanation
      for HF formation, and thus for the detrimental effects of HF on reproductive
      processes and IVF outcome.

PMID- 16105744
TI  - A multifrequency EPR approach to travertine characterisation.
AB  - The understanding of processes that give rise to travertine deposits is
      important. This is so because of its widespread use as decorative material, but
      more so in environmental studies due to the significance, by proxy, of travertine
      in climatology. In this paper, a multifrequency EPR spectroscopy study of the
      behaviour of an ubiquitary vicariant of Ca in calcite, Mn(II), is presented. EPR
      spectra were obtained from a natural sample at 9.5 (X-band), 95, 190, and 285GHz,
      and interpreted through numerical simulation. An analysis of the distribution of
      the zero-field splitting interaction revealed the source of some unexpected
      spectral features in the width of the lines in the X-band. By contrast, the
      homogeneous broadening plays only a minor role. Moreover, field-dependent
      anisotropies of the Zeeman and hyperfine tensors were observed at higher
      frequency. On the basis of results garnered in this study, the ZFS interaction of
      Mn(II) has been ascribed to the microstructural anomalies of the Mn(II)
      distribution in calcite. This may be considered as the fingerprint of the
      physical-chemical conditions at the time of travertine deposition. As a
      consequence, X-band EPR spectroscopy represents a specific tool to investigate
      the genesis, and to check the homogeneity of Mn(II) distribution in travertines
      as well as in other calcite-based materials.

PMID- 16105745
TI  - Perceptions of effort during handgrip and tongue elevation in Parkinson's
      disease.
AB  - BACKGROUND: Fatigue and the accompanying perception of effort are often
      heightened in Parkinson's disease. OBJECTIVES: To compare performance on three
      sense-of-effort tasks between patients with PD and matched neurologically normal
      control subjects. METHODS: Sixteen PD subjects and 16 normal subjects performed
      three tasks to assess sense of effort: self-ratings of effort using direct
      magnitude estimation, generating pressures at various levels of effort, and
      sustaining a submaximal level of effort. The latter two tasks were done with
      handgrip and tongue elevation. RESULTS: Two of the three tasks successfully
      differentiated the groups. Subjects with PD provided significantly higher ratings
      of effort for general daily activities and for speech. During the constant-effort
      task, pressure curves decayed more rapidly for the PD subjects. CONCLUSIONS:
      Performance by PD subjects on the constant-effort task resembled that by normal
      adults who were pre-fatigued in previous experiments. Results support greater
      than normal sense-of-effort related to fatigue in PD, and provide preliminary
      validation of a performance-based physiologic task to assess abnormal sense of
      effort in this population.

PMID- 16105746
TI  - The pivotal role of cytokines in muscle wasting during cancer.
AB  - The cachectic syndrome, characterized by a marked weight loss, anorexia, asthenia
      and anemia, is invariably associated with the presence and growth of the tumour
      and leads to a malnutrition status due to the induction of anorexia or decreased
      food intake. In addition, the competition for nutrients between the tumour and
      the host leads to an accelerated catabolic state, which promotes severe metabolic
      disturbances in the host, including hypermetabolism, which leads to an increased
      energetic inefficiency. Although the search for the cachectic factor(s) started a
      long time ago, and although many scientific and economic efforts have been
      devoted to its discovery, we are still a long way from knowing the whole truth.
      Present investigation is devoted to unrevealing the different signaling pathways
      (particulary transcriptional factors) involved in muscle wasting. The main aim of
      the present review is to summarize and evaluate the different molecular
      mechanisms and catabolic mediators involved in cancer cachexia since they may
      represent targets for future promising clinical investigations.

PMID- 16105747
TI  - GSTM1 [corrected] deletion modifies the levels of polycyclic aromatic hydrocarbon
      DNA adducts in human sperm.
AB  - DNA adducts measured in tissues are promising markers for identifying damage in
      organs that could be a target for carcinogens. Polymorphisms in genes involved in
      polycyclic aromatic hydrocarbons (PAHs) metabolism have been shown to modify the
      levels of PAH-DNA adducts in target tissues. In order to study the role of
      metabolic gene polymorphisms on DNA-adduct formation in sperm, we determined the
      GSTM1 genotype in a group of men in whom PAH-DNA adducts in sperm had been
      previously measured by immunofluorescence. The mean level of adducts in sperm was
      significantly higher in subjects carrying the homozygous deletion variant of
      GSTM1 than in subjects with a functional GSTM1 (mean fluorescence staining
      intensity: 1.62+/-0.62 versus 1.33+/-0.55; p=0.02). With respect to environmental
      factors, subjects who reported occupational exposure to PAHs and who carried the
      GSTM1 deletion had a significant increase in PAH-DNA adducts in sperm in
      comparison with subjects who were not exposed and had a functional GSTM1 (mean
      staining intensity: 1.83+/-0.67 versus 1.30+/-0.53; p=0.05), although among GSTM1
      null subjects there was no significant difference with or without occupational
      exposure. This study presents for the first time the effect of a common
      polymorphism in a gene that metabolizes PAHs on DNA-adduct levels in sperm.

PMID- 16105748
TI  - Chinese version of the parent-proxy health-related quality of life measure for
      children with epilepsy: translation, cross-cultural adaptation, and reliability
      studies.
AB  - PURPOSE: The goal of this article is to report on the translation and reliability
      studies of the Parent-Proxy Response Scale of Quality of Life Measure for
      Children with Epilepsy for Hong Kong Chinese children. METHODS: In phase 1,
      forward and backward translations, expert panel review, and a series of pilot
      testing, cognitive interviewing, and pretesting with parents produced a Chinese
      translation. Content validity of the translated instrument was assessed. In phase
      2, internal consistency was evaluated in 40 parents of children with epilepsy
      aged 8 to 18. Test-retest reliability was studied in 33 parents. RESULTS: The
      translation was judged to have good content validity by experts and was
      acceptable to parents. Internal consistency was good (Cronbach alpha=0.71-0.92).
      Test-retest reliability, determined with the intraclass correlation coefficient,
      ranged between 0.51 and 0.84. CONCLUSIONS: Our data suggest acceptable content
      validity, internal consistency, and reliability of the Chinese version of the
      Parent-Proxy Response Scale of the Quality of Life Measure for Children with
      Epilepsy. Studies with larger samples should be performed to further confirm
      other psychometric properties of the translated instrument.

PMID- 16105749
TI  - Computer simulation of epilepsy: implications for seizure spread and behavioral
      dysfunction.
AB  - Hippocampal area CA3 has been one of the most intensively studied brain regions
      for computer models of epileptiform activity. As physiological studies begin to
      extend outward to other hippocampal and parahippocampal areas, we must extend
      these models to understand more complex circuitry containing diverse elements.
      Study of subiculum is of particular interest in this context, as it is a
      structure of intermediate complexity, with an inchoate columnar and laminar
      organization. In addition to helping us understand seizures, modeling of these
      structures will also help us understand the genesis of physiological activity
      patterns that are below threshold for seizure generation. Such modeling can also
      serve as a basis for speculation regarding the nonictal behavioral consequences
      of epilepsy.

PMID- 16105750
TI  - Recurrent autonomic status epilepticus in Panayiotopoulos syndrome: video/EEG
      studies.
AB  - We describe a neurologically and developmentally normal child with infrequent
      seizures characterized by emetic symptoms and other autonomic phenomena and
      interictal spikes that satisfy the diagnostic criteria of Panayiotopoulos
      syndrome (PS). Two video/EEG recordings, taken a year apart, revealed prolonged
      autonomic seizures and other subtle behavioral changes, suggesting that episodes
      of nonconvulsive status epilepticus in PS may be more frequent than appreciated.

PMID- 16105753
TI  - Runx1/AML1 in normal and abnormal hematopoiesis.
AB  - Runx1/AML1 (also known as CBFA2 and PEBP23B) is a Runt family transcription
      factor critical for normal hematopoiesis. Runx1 forms a heterodimer with CBF3 and
      binds to the consensus PEBP2 sequence through the Runt domain. Runx1 enhances
      gene transcription by interacting with transcriptional coactivators such as p300
      and CREB-binding protein. However, Runx1 can also suppress gene transcription by
      interacting with transcriptional corepressors, including mSin3A, TLE (mammalian
      homolog of Groucho), and histone deacetylases. Runx1 not only is critical for
      definitive hematopoiesis in the fetus but also is required for normal
      megakaryocytic maturation and T-lymphocyte and B-lymphocyte development in adult
      mice. Runx1 has been identified in leukemia-associated chromosomal
      translocations, including t(8;21) (Runx1-ETO/MTG8), t(16;21) (Runx1-MTG16),
      t(3;21) (Runx1-Evi1), t(12;21) (TEL-Runx1), and t(X;21) (Runx1-Fog2). The
      molecular mechanism of leukemogenesis by these fusion proteins is discussed.
      Various mutant mice expressing these fusion proteins have been created. However,
      expression of the fusion protein is not sufficient by itself to cause leukemia
      and likely requires additional events for leukemogenesis. Point mutations in a
      Runx1 allele cause haploinsufficiency and a biallelic null for Runx1, which are
      associated with familial platelet disorder with a propensity for acute myeloid
      leukemia (FPD/AML) and AML-M0, respectively. Thus, the correct protein structure
      and the precise dosage of Runx1 are essential for the maintenance of normal
      hematopoiesis.

PMID- 16105754
TI  - Molecular pathogenesis of MLL-associated leukemias.
AB  - Chromosome translocations disrupting the MLL gene are associated with various
      hematologic malignancies but are particularly common in infant and secondary
      therapy-related acute leukemias. The normal MLL-encoded protein is an essential
      component of a supercomplex with chromatin-modulating activity conferred by
      histone acetylase and methyltransferase activities, and the protein plays a key
      role in the developmental regulation of gene expression, including Hox gene
      expression. In leukemia, this function is subverted by breakage, recombination,
      and the formation of chimeric fusion with one of many alternative partners. Such
      MLL translocations result in the replacement of the C-terminal functional domains
      of MLL with those of a fusion partner, yielding a newly formed MLL chimeric
      protein with an altered function that endows hematopoietic progenitors with self
      renewing and leukemogenic activity. This potent impact of the MLL chimera can be
      attributed to one of 2 kinds of activity of the fusion partner: direct
      transcriptional transactivation or dimerization/oligomerization. Key unresolved
      issues currently being addressed include the set of target genes for MLL fusions,
      the stem cell of origin for the leukemias, the role of additional secondary
      mutations, and the origins or etiology of the MLL gene fusions themselves.
      Further elaboration of the biology of MLL gene-associated leukemia should lead to
      novel and specific therapeutic strategies.

PMID- 16105755
TI  - NUP98 fusion in human leukemia: dysregulation of the nuclear pore and homeodomain
      proteins.
AB  - NUP98 is fused to a variety of partner genes, including abdominal B-like HOX, in
      human myeloid and T-cell malignancies via chromosomal translocation involving
      11p15. NUP98 encodes a 98-kd nucleoporin that is a component of the nuclear pore
      complex and functions in nucleocytoplasmic transport, with its N-terminal GLFG
      repeats used as a docking site for karyopherins. Disruption of NUP98 may affect
      the nuclear pore function, and the abnormal expression and altered function of
      fusion partners may also be critical for leukemia development. Recent studies
      using mouse models expressing NUP98-HOX have confirmed its leukemogenic
      potential, and cooperative genes for NUP98-HOXA9 in leukemogenesis have been
      identified in these studies.Thus, the NUP98 chimera is a unique molecule that
      provides valuable information regarding nuclear pore function and the role of the
      homeobox protein in leukemogenesis/carcinogenesis.

PMID- 16105756
TI  - Intensive immunosuppression therapy for aplastic anemia associated with
      dyskeratosis congenita: report of a case.
AB  - Dyskeratosis congenita (DC) is a very rare inherited disorder characterized by
      skin pigmentation, nail dystrophy, and mucosal leukoplakia. It is also associated
      with a variety of noncutaneous abnormalities, such as fatal pulmonary
      complications, malignancy, and bone marrow failure. We report the case of a 32
      year-old man with DC associated with severe aplastic anemia (SAA). The
      traditional treatment of DC-associated SAA is allogeneic hematopoietic stem cell
      transplantation (HSCT). However, in this case, an HLA-matched donor was not
      available. Therefore our patient was given intensive immunosuppressive therapy
      with antilymphocyte globulin (ALG) and cyclosporine A (CsA). The hemogram
      findings improved after the treatment, but the patient died of pulmonary
      complications after being in stable condition for 6 months. The results support
      the possible use of intensive immunosuppression with ALG and CsA for DC
      associated SAA as an alternative treatment for patients who are not eligible for
      HSCT.

PMID- 16105757
TI  - Identification of a chromosomal breakpoint and detection of a novel form of an
      MLL-AF17 fusion transcript in acute monocytic leukemia with t(11;17)(q23;q21).
AB  - More than 40 genes have been reported as translocation partners of the mixed
      lineage leukemia gene (MLL) in hematologic malignancies. AF17 was identified
      earlier than most other MLL translocation partners. On the other hand, there is
      only 1 report of an MLL-AF17 fusion transcript in acute myeloid leukemia (AML).
      Here we describe a 40-year-old man with a diagnosis of AML involving
      t(11;17)(q23;q21). We identified a chromosomal breakpoint for t(11;17)(q23;q21)
      at MLL intron 6 and AF17 intron 8. Although the previously reported form of the
      MLL-AF17 fusion transcript was not detected by reverse transcriptase-polymerase
      chain reaction (PCR) analysis, a novel form of an MLL-AF17 fusion transcript
      joining MLL exon 6 to AF17 exon 9 was detected by complementary DNA panhandle
      PCR. The fact that 2 forms of MLL-AF17 retain the leucine zipper domain of AF17
      suggests that the dimerization domain of AF17 is critical for leukemogenesis by
      the MLL-AF17 fusion gene.

PMID- 16105758
TI  - BMI-1 is highly expressed in M0-subtype acute myeloid leukemia.
AB  - Recent studies have suggested that one of the polycomb group genes, BMI-1, has an
      important role in the maintenance of normal and leukemic stem cells by repressing
      the INK4a/ARF locus. Here, we quantitatively examined BMI-1 expression level in
      samples from patients with acute myeloid leukemia (AML) and other hematologic
      malignancies. Moderate to high BMI-1 expression was detected in AML patients, and
      the BMI-1 expression levels in AML samples were significantly higher than in
      normal bone marrow controls (P = .0011). Specimens of French-American-British
      classification subtype M0 showed higher relative expression of the BMI-1
      transcript (median, 390.2 3 10(-3)) than the other subtypes (median, 139.0 3 10(
      3)) (P < .0001). Leukemia other than AML showed low to moderate expression. INK4a
      ARF transcript expression tended to be inverse proportion to that of BMI-1. In an
      M0 patient with a high BMI-1 transcript level, the INK4a-ARF transcript level
      fell promptly and maintained a low value after the patient achieved complete
      remission. These results indicated that a subgroup of M0 patients has a high
      expression level of polycomb group gene BMI-1, which may contribute to
      leukemogenesis.

PMID- 16105759
TI  - Aclarubicin and low-dose Cytosine arabinoside in combination with granulocyte
      colony-stimulating factor in treating acute myeloid leukemia patients with
      relapsed or refractory disease and myelodysplastic syndrome: a multicenter study
      of 112 Chinese patients.
AB  - One hundred twelve patients with geriatric acute myeloid leukemia (AML),
      refractory or relapsed AML, or myelodysplastic syndrome and refractory anemia
      with excess of blasts in transformation (MDS-RAEBt) were entered into this study
      to receive CAG (aclarubicin and low-dose cytosine arabinoside [Ara-C]in
      combination with granulocyte colony-stimulating factor [G-CSF]) with the
      objective of evaluating the efficacy and tolerance of this regimen. Low-dose Ara
      C was given subcutaneously at a dosage of 10 mg/m2 every 12 hours on days 1 to
      14. Aclarubicin was administered intravenously at a dosage of 14 mg/m2 per day on
      days 1 to 4 (CAG regimen A) or 7 mg/m2 on days 1 to 8 (CAG regimen B).
      Recombinant G-CSF was given subcutaneously at a dosage of 200 3g/m2 per day on
      days 1 to 14. We demonstrated comparable overall complete remission rates for the
      4 groups of patients: 30.8% (8/26) in the elderly patients, 48.4% (30/62) in the
      refractory AML patients, 44.4% (8/18) in the relapsed AML patients, and 38.5%
      (5/13) in the MDS-RAEBt patients. Of the 52 patients followed up, the 12-month
      progression-free survival (PFS) and overall survival (OS) rates estimated by the
      Kaplan-Meier method were 40.73% 3 8.15% and 42.85% 3 8.23%, respectively. The
      median PFS and OS times were 9.0 3 2.2 months and 11.0 3 1.6 months,
      respectively. Toxic effects were very rare and mainly consisted of neutropenia
      and thrombocytopenia due to myelosuppression; approximately 70% to 80% of
      patients had neutropenia or thrombocytopenia that exceeded National Cancer
      Institute grade II. Nonhematologic toxicities were not observed in this study.
      The CAG regimen seems promising, with acceptable toxicity, for the treatment of
      various categories of poor-prognosis AML and MDS-RAEBt.

PMID- 16105760
TI  - X-linked lymphoproliferative disease in an adult.
AB  - X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency
      characterized by an extreme susceptibility to Epstein-Barr virus (EBV) infection.
      Patients with XLP mainly present with the 3 clinical manifestations of fulminant
      infectious mononucleosis, lymphoproliferative disorder, and dysgammaglobulinemia
      and in rare cases have aplastic anemia and lymphocytic vasculitis. The causative
      gene for XLP was identified as SH2D1A/DSHP/SLAM-associated protein (SAP) in 1998,
      and genetic analysis has been used for the definite diagnosis of XLP. Diagnosis
      for most patients occurs at ages younger than 10 years, and there are few adult
      patients. Here we describe a 23-year-old man with hypogammaglobulinemia and EBV
      associated hemophagocytic lymphohistiocytosis and a diagnosis of XLP. In
      addition, the patient showed type 1 helper T-cell (Th1) skewing, as has been
      described in Sap knock-out mice. Th1/Th2 imbalance in humans, as well as in mice,
      may play an important role in the pathogenesis of XLP.

PMID- 16105761
TI  - Detection of API2-MALT1 fusion transcripts in cytologic specimens of patients
      with pulmonary mucosa-associated lymphoid tissue lymphoma.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma constitutes up to 90% of
      primary pulmonary lymphomas, but its diagnosis is often difficult. API2-MALT1
      fusion is specific to MALT lymphoma and is detected in nearly half of the
      pulmonary cases. Cytologic examinations have played a pivotal role in the
      diagnosis of pulmonary tumors; however, cytologic specimens have only
      infrequently been used for molecular studies. In this study, we performed a
      multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay to
      detect the API2-MALT1 fusion transcript in archival cytologic specimens used as
      RNA sources. We studied 3 pulmonary MALT lymphoma cases that were positive for
      the fusion gene as detected with RNA extracted from diagnostic histologic
      specimens. In 1 case, a conventional PCR clonality assay for the immunoglobulin
      heavy chain gene rearrangement failed to detect the monoclonality. In all 3
      cases, the fusion transcript was successfully detected in the cytologic specimens
      of sputum, bronchoalveolar lavage fluid, bone marrow smears, and pleural
      effusions. This finding suggests that such specimens can be used as RNA sources
      in multiplex RT-PCR assays for the API2-MALT1 fusion transcript. The detection of
      API2-MALT1 fusion as carried out with these specimens would be useful as an
      ancillary assay for the diagnosis, staging, and follow-up of pulmonary MALT
      lymphoma.

PMID- 16105762
TI  - Meningeal lymphomatosis as the first manifestation of splenic marginal zone
      lymphoma.
AB  - Meningeal lymphomatosis (ML) as the first manifestation of a splenic marginal
      zone lymphoma (SMZL) is rare. The descriptions of only 2 cases with this
      complication, one of which had ML as the first manifestation, have been published
      to date. We describe a 53-year-old man, an ex-smoker, who presented with
      transitory episodes of bilateral loss of visual acuity. On examination, only
      papilledema and splenomegalia were observed. The hemogram showed a predominance
      of lymphocytes with a villous morphology. Cytochemical staining and an
      immunophenotypic analysis revealed a positive reaction to tartrate-sensitive acid
      phosphatase and B-lineage markers (CD19+, CD20+, CD79b+, surface immunoglobulin 3
      expression, immunoglobulin D+, CD5-, CD23-, CD10-, CD25-, CD103-, and CD11c-).
      Magnetic resonance imaging of the brain showed tumoral infiltration in both optic
      nerves and in the cervicodorsal meninges. The cerebrospinal fluid examination
      revealed significant pleocytosis, and all lymphocytes had a phenotype identical
      to that of the peripheral blood, confirming the presence of ML. The bone marrow
      section also showed lymphocytes with an immunophenotype identical to that of the
      peripheral blood.A splenectomy confirmed the SMZL diagnosis. Treatment with
      corticosteroids and intrathecal chemotherapy was administrated; however, the
      response was not good, and the patient died. In this report, we discuss the other
      2 cases and ML in B-cell chronic lymphoproliferative disorders.

PMID- 16105763
TI  - Comparison of 2 preparative regimens for stem cell transplantation from HLA
      matched sibling donors in patients with advanced myelodysplastic syndrome.
AB  - The objective of this study was to compare how cyclophosphamide (CY) and oral
      busulfan (BU) therapies, each in combination with total body irradiation (TBI),
      affect the outcome of stem cell transplantation in patients with advanced
      myelodysplastic syndrome. This study was conducted with 31 patients who received
      bone marrow from an HLA-matched sibling and underwent treatment with BU-TBI (n =
      18) or CY-TBI (n = 13). The incidence of acute graft-versus-host disease (GVHD)
      grades II to IV was higher, but not significantly, in the BU-TBI group (58.8%)
      than in the CY-TBI group (30.8%). However, the incidences of chronic extensive
      GVHD were significantly different (41.7% [CY-TBI] versus 80.0% [BU-TBI], P =
      .04). Trends after BU-TBI conditioning indicated a lower 3-year probability of
      disease-free survival (DFS) (38.1% versus 53.9%, P = .4), lower relapse rates
      (28.5% versus 36.4%, P = .8), and higher nonrelapse mortality rates (46.7% versus
      15.4%, P = .2). After adjusting for the International Prognostic Scoring System
      risk group and the cytogenetic risk group, DFS in the CY-TBI group (relative
      risk, 9.0; 95% confidence interval, 1.5-52.5; P = .015) was found to be
      significantly increased compared with the BU-TBI group. Approaches to minimize
      transplantation-related toxicity should be pursued, and efforts other than the
      potentiation of the conditioning regimen should be made to reduce the likelihood
      of posttransplantation relapse.

PMID- 16105764
TI  - A novel chromosomal abnormality, t(6;10)(q27;q22), found in a polycythemic
      potential donor for allogeneic hematopoietic stem cell transplantation.
AB  - A 59-year-old man was a potential donor for allogeneic hematopoietic stem cell
      transplantation and was found to be healthy but slightly polycythemic. The bone
      marrow was morphologically normal, but karyotyping of bone marrow cells showed
      t(6;10)(q27;q22) in 7 of 20 metaphases analyzed by G-banding and only the t(6;10)
      abnormality in 3 of 5 metaphases analyzed by the spectral karyotyping method. G
      banding analysis of peripheral blood mononuclear cells cultured with
      phytohemagglutinin for 72 hours showed a normal karyotype in all 20 metaphases
      analyzed.These findings suggest clonal expansion with t(6;10)(q27;q22) in the
      bone marrow of this individual. He was determined to be ineligible for donation.
      A coordinated nationwide work-up for older donors is necessary to ensure high
      quality standards.

PMID- 16105766
TI  - New developments and applications in rapid fluid flows. Proceedings of a
      workshop. July 14-18, 2003. Durham University, United Kingdom.

PMID- 16105765
TI  - Granulocyte colony-stimulating factor-primed donor lymphocyte infusion after
      salvage chemotherapy for treatment of relapsed acute leukemia after allogeneic
      stem cell transplantation.

PMID- 16105767
TI  - Multi-branching flows from one mother tube to many daughters or to a network.
AB  - Multiply branching fluid flows are modelled in two contexts. The first (type I)
      is for one-to-many branching. Computations are described for flow through a
      channel, with fully developed motion upstream, which branches abruptly into a
      number of subchannels downstream. The differences in pressure between the
      upstream end of the channel and the downstream ends of the subchannels are
      substantial. Comparisons with recent analytical predictions show fair agreement
      for Reynolds numbers in the low tens and above. The second context (type II) has
      successive generations of bifurcation in a network. Modelling, computations and
      analysis include the effects of many bifurcations.

PMID- 16105768
TI  - Blow-up and control of marginally separated boundary layers.
AB  - Interactive solutions for steady two-dimensional laminar marginally separated
      boundary layers are known to exist up to a critical value Gamma(c) of the
      controlling parameter (e.g. the angle of attack of a slender airfoil) Gamma only.
      Here, we investigate three-dimensional unsteady perturbations of such boundary
      layers, assuming that the basic flow is almost critical, i.e. in the limit
      Gamma(c)-Gamma-->0. It is then shown that the interactive equations governing
      such perturbations simplify significantly, allowing, among others, a systematic
      study of the blow-up phenomenon observed in earlier investigations and the
      optimization of devices used in boundary-layer control.

PMID- 16105769
TI  - Modelling the calmed region behind a spot.
AB  - A theoretical model of the laminar 'calmed region' following a three-dimensional
      turbulent spot within a transitioning two-dimensional boundary layer is
      formulated and discussed. The flow is taken to be inviscid, and the perturbation
      mean flow surface streamlines calculated represent disturbances to the basic slip
      velocity. Available experimental evidence shows a fuller, more stable, streamwise
      profile in a considerable region trailing the spot, with cross-flow 'inwash'
      towards the line of symmetry. Present results are in qualitative agreement with
      this evidence.

PMID- 16105770
TI  - Towards transition modelling for supersonic laminar flow control based on
      spanwise periodic roughness elements.
AB  - Laminar flow control (LFC) is one of the key enabling technologies for quiet and
      efficient supersonic aircraft. Recent work at Arizona State University (ASU) has
      led to a novel concept for passive LFC, which employs distributed leading edge
      roughness to limit the growth of naturally dominant crossflow instabilities in a
      swept-wing boundary layer. Predicated on nonlinear modification of the mean
      boundary-layer flow via controlled receptivity, the ASU concept requires a
      holistic prediction approach that accounts for all major stages within transition
      in an integrated manner. As a first step in developing an engineering methodology
      for the design and optimization of roughness-based supersonic LFC, this paper
      reports on canonical findings related to receptivity plus linear and nonlinear
      development of stationary crossflow instabilities on a Mach 2.4, 73 degrees swept
      airfoil with a chord Reynolds number of 16.3 million.

PMID- 16105771
TI  - Streaks and vortices in near-wall turbulence.
AB  - This paper presents evidence that organization of wall-normal motions plays
      almost no role in the creation of streaks. This evidence consists of the theory
      of streak generation not requiring the existence of organized vortices, extensive
      quantitative comparisons between the theory and direct numerical simulations,
      including examples of large variation in average spacing of the streaks of
      different scalars simultaneously present in the flow, and an example of the
      scalar streaks in an artificially created purely random flow.

PMID- 16105772
TI  - Numerical simulation of boundary-layer disturbance evolution.
AB  - The use of numerical simulations to study the development of boundary-layer
      disturbances is illustrated for a number of different incompressible flow
      configurations. These include cases where the disturbances are generated by, or
      interact with, flow-control devices in the form of compliant panels, suction
      slots and microelectromechanical systems actuators. The velocity-vorticity system
      of governing equations used for the simulations is reviewed, along with the
      numerical discretization.

PMID- 16105773
TI  - Long-wave theory for a new convective instability with exponential growth normal
      to the wall.
AB  - A linear stability theory is presented for the boundary-layer flow produced by an
      infinite disc rotating at constant angular velocity in otherwise undisturbed
      fluid. The theory is developed in the limit of long waves and when the effects of
      viscosity on the waves can be neglected. This is the parameter regime recently
      identified by the author in a numerical stability investigation where a curious
      new type of instability was found in which disturbances propagate and grow
      exponentially in the direction normal to the disc, (i.e. the growth takes place
      in a region of zero mean shear). The theory describes the mechanisms controlling
      the instability, the role and location of critical points, and presents a saddle
      point analysis describing the large-time evolution of a wave packet in frames of
      reference moving normal to the disc. The theory also shows that the previously
      obtained numerical solutions for numerically large wavelengths do indeed lie in
      the asymptotic long-wave regime, and so the behaviour and mechanisms described
      here may apply to a number of cross-flow instability problems.

PMID- 16105774
TI  - Absolute instability of the von Karman, Bodewadt and Ekman flows between a
      rotating disc and a stationary lid.
AB  - The stability of a family of boundary-layer flows, which includes the von Karman,
      Bodewadt and Ekman flows for a rotating incompressible fluid between a rotating
      disc and a stationary lid, is investigated. Numerical computations with the use
      of a spectral method are carried out to analyse absolute and convective
      instability. It is shown that the stability of the system is enhanced with a
      decrease in distance between the disc and the lid.

PMID- 16105775
TI  - Receptivity of boundary layers to distributed wall vibrations.
AB  - Linear three-dimensional receptivity of boundary layers to distributed wall
      vibrations in the large Reynolds number limit (Re-->infinity) is studied in this
      paper. The fluid motion is analysed by means of the multiscale asymptotic
      technique combined with the method of matched asymptotic expansions. The body
      surface is assumed to be perturbed by small-amplitude oscillations being tuned in
      resonance with the neutral Tollmien-Schlichting wave at a certain point on the
      wall. The characteristic length of the resonance region is found to be O(Re
      3/16), which follows from the condition that the boundary-layer non-parallelism
      and the wave amplitude growth have the same order of magnitude. The amplitude
      equation is derived as a solvability condition for the inhomogeneous boundary
      value problem. Investigating detuning effects, we consider perturbations in the
      form of a wave packet with a narrow O(Re-3/16) discrete or continuous spectrum
      concentrated near the resonant wavenumber and frequency. The boundary-layer
      laminarization based on neutralizing the oncoming Tollmien-Schlichting waves (or
      wave packets) is also discussed.

PMID- 16105776
TI  - An effective numerical method for solving viscous-inviscid interaction problems.
AB  - This paper presents a new numerical method to solve the equations of the
      asymptotic theory of separated flows. A number of measures was taken to ensure
      fast convergence of the iteration procedure, which is employed to treat the
      nonlinear terms in the governing equations. Firstly, we selected carefully the
      set of variables for which the nonlinear finite difference equations were
      formulated. Secondly, a Newton-Raphson strategy was applied to these equations.
      Thirdly, the calculations were facilitated by utilizing linear approximation of
      the boundary-layer equations when calculating the corresponding Jacobi matrix.
      The performance of the method is illustrated, using as an example, the problem of
      laminar two-dimensional boundary-layer separation in the flow of an
      incompressible fluid near a corner point of a rigid body contour. The solution of
      this problem is non-unique in a certain parameter range where two solution
      branches are possible.

PMID- 16105777
TI  - Some models of viscous-inviscid interaction.
AB  - Some hydrodynamical problems in which viscous-inviscid interaction is important
      are analysed. These problems are: disturbances propagation in channels, three
      dimensional nonlinearly disturbed flows and the blow-off phenomenon.

PMID- 16105778
TI  - Stability of Bodewadt flow.
AB  - The stability of the flow produced over an infinite stationary plane in a fluid
      rotating with uniform angular velocity at an infinite distance from the plane is
      considered. The basic flow is an exact solution of the Navier-Stokes equations
      making it amenable to theoretical study. An asymptotic investigation is presented
      in the limit of large Reynolds number. It is shown that the stationary spiral
      instabilities observed experimentally can be described by a linear inviscid
      stability analysis. The prediction obtained for the wave angle of the
      disturbances is found to agree well with the available experimental and numerical
      results.

PMID- 16105779
TI  - On the ejection-induced instability in Navier-Stokes solutions of unsteady
      separation.
AB  - Numerical solutions of the flow induced by a thick-core vortex have been obtained
      using the unsteady, two-dimensional Navier-Stokes equations. The presence of the
      vortex causes an adverse pressure gradient along the surface, which leads to
      unsteady separation. The calculations by Brinckman and Walker for a similar flow
      identify a possible instability, purported to be an inviscid Rayleigh
      instability, in the region where ejection of near-wall vorticity occurs during
      the unsteady separation process. In results for a range of Reynolds numbers in
      the present investigation, the oscillations are also found to occur. However,
      they can be eliminated with increased grid resolution. Despite this behaviour,
      the instability may be physical but requires a sufficient amplitude of
      disturbances to be realized.

PMID- 16105780
TI  - Vortices and flow reversal due to suction slots.
AB  - Suction into small two- or three-dimensional surface slots inside an otherwise
      planar boundary-layer is examined theoretically through a combined analytical and
      computational approach. Increasing suction strength leads to enhanced nonlinear
      structures with flow reversals or trailing vortices.

PMID- 16105781
TI  - Droplet impact on water layers: post-impact analysis and computations.
AB  - An inviscid model of droplet impact into a water layer is examined analytically
      for small times just after impact and computationally for order-one distortion
      times. Various layer depths are considered, as are surface-tension effects. Good
      correspondence is found between analysis, computation and experiments.

PMID- 16105782
TI  - The linear and nonlinear stability of thread-annular flow.
AB  - The surgical technique of thread injection of medical implants is modelled by the
      axial pressure-gradient-driven flow between concentric cylinders with a moving
      core. The linear stability of the flow to both axisymmetric and asymmetric
      perturbations is analysed asymptotically at large Reynolds number, and
      computationally at finite Reynolds number. The existence of multiple regions of
      instability is predicted and their dependence upon radius ratio and thread
      velocity is determined. A discrepancy in critical Reynolds numbers and cut-off
      velocity is found to exist between experimental results and the predictions of
      the linear theory. In order to account for this discrepancy, the high Reynolds
      number, nonlinear stability properties of the flow are analysed and a nonlinear,
      equilibrium critical layer structure is found, which leads to an enhanced
      correction to the basic flow. The predictions of the nonlinear theory are found
      to be in good agreement with the experimental data.

PMID- 16105783
TI  - Transient feedback and global instability in non-homogeneous systems.
AB  - Model examples of linear wave systems are considered to illustrate the origin of
      feedback instability in situations involving strong transients. Two mechanisms of
      transient growth are addressed. The first is a spatial amplification of resonant
      waves propagating in the same direction. The second form of transient growth is
      purely temporal. It is found that under certain conditions, both forms of
      transients can trigger global instability in a non-homogeneous system.

PMID- 16105784
TI  - Asymptotic approach to combustion instability.
AB  - This paper presents an asymptotic approach to combustion instability in premixed
      flames under the assumptions of large activation energy and small Mach number.
      The entire flow consists of four distinct yet fully interactive sub-regions,
      which accommodate the chemical reaction, heat transport, hydrodynamics and
      acoustics, respectively. A reduced system was derived to describe the intricate
      coupling between the flame and acoustics that underlies the combustion
      instability. The asymptotically reduced system was employed to study the weakly
      nonlinear interaction between the Darrieus-Landau instability and the
      longitudinal acoustic mode of the combustion chamber. The general asymptotic
      formulation includes the influence of enthalpy fluctuation in the oncoming
      mixture. It is shown that one-dimensional enthalpy fluctuation, through its
      interaction with flame, produces sound waves, and may cause parametric
      instability of the flame. The mutual coupling between the sound wave and
      parametric instability is analysed at the instability thresholds.

PMID- 16105785
TI  - Transplacental effects of allopurinol on suppression of oxygen free radical
      production in chronically instrumented fetal lamb brains during intermittent
      umbilical cord occlusion.
AB  - OBJECTIVE: To evaluate the transplacental effect of allopurinol, which acts as a
      xanthine oxidase inhibitor and free radical scavenger, on inhibiting the
      production of superoxides during intermittent partial umbilical cord occlusion.
      METHODS: Using four chronically instrumented fetal lambs, ewes received 400 mg
      allopurinol over a period of two hours. Concentrations of allopurinol and
      oxypurinol in blood samples from mothers and fetuses and fetal brain
      microdialysis perfusate were measured by HPLC. In another three cases the
      production of superoxide during intermittent umbilical cord occlusion was studied
      by measurement of chemiluminescence in perfusate before and after administration
      of Allopurinol. RESULTS: (i) Allopurinol concentration in mothers had reached
      equilibrium by 30 min after starting administration and maintained a
      concentration about 6 mug/ml. Allopurinol concentration in fetuses increased
      gradually and reached 2.25 +/- 0.54 microg/ml at 120 min; (ii) Oxypurinol
      concentration in both mothers and fetuses increased during administration of
      allopurinol; (iii) Concentrations of allopurinol and oxypurinol in the perfusates
      reached 0.32 +/- 0.12 microg/ml, 0.53 +/- 0.22 microg/ml at 120 min respectively;
      and (iv) Administration of allopurinol significantly suppressed superoxide
      production during intermittent partial umbilical cord occlusion. CONCLUSION:
      These results demonstrated a good transfer of allopurinol from mother to fetus
      and suggested the possibility of intrauterine treatment to inhibit fetal brain
      damage resulting from increased oxygen free radicals.

PMID- 16105786
TI  - Evidence supporting that the excess of the sVEGFR-1 concentration in maternal
      plasma in preeclampsia has a uterine origin.
AB  - BACKGROUND: Preeclampsia has been considered an anti-angiogenic state. Two
      factors have been implicated in the genesis of this state: soluble vascular
      endothelial growth factor receptor-1 (sVEGFR-1) and placental growth factor
      (PlGF). Indeed, the concentrations of PlGF, an angiogenic factor, are lower in
      preeclampsia than in normal pregnancy, while the opposite is the case for the
      anti-angiogenic factor, sVEGFR-1. The source of the excess sVEGFR-1 has not yet
      been determined. Since the placenta could be a source of sVEGFR-1, we conducted a
      study to determine whether there is a gradient in the plasma concentration of
      sVEGFR-1 and PlGF between the uterine vein and the antecubital vein in both
      patients with preeclampsia and normal pregnant women. METHODS: A cross-sectional
      study was performed to determine the plasma concentrations of sVEGFR-1 and PlGF
      in the uterine and antecubital vein of patients with preeclampsia (n = 9) and
      normal pregnant women at term (n = 9). Plasma samples were collected from
      antecubital and uterine veins at the time of cesarean section. The concentrations
      of sVEGFR-1 and PlGF were determined using specific enzyme-linked immunoassays.
      The differences of plasma concentrations of sVEGFR-1 and PlGF between uterine and
      antecubital veins in both groups were compared by paired t-tests. RESULTS:
      Patients with preeclampsia had a significantly higher mean plasma concentration
      of sVEGFR-1 in the uterine vein than in the antecubital vein (uterine vein: mean
      13,675 +/- 5,684 pg/ml vs. antecubital vein: mean 10,234 +/- 4,700 pg/ml; paired
      t-tests, p = 0.04). In contrast, among normal pregnant women at term, there was
      no significant difference in plasma concentrations of sVEGFR-1 between the
      uterine and antecubital veins (uterine vein: mean 1,918 +/- 665 pg/ml vs.
      antecubital vein: mean 1,750 +/- 475 pg/ml; paired t-tests, p = 0.1). The mean
      plasma concentration of sVEGFR-1, either in the antecubital or uterine vein, was
      significantly higher in preeclampsia than in normal pregnancy (unpaired t-tests;
      both p < 0.001). There was no significant difference in the mean plasma
      concentration of PlGF between the uterine and the antecubital veins in both the
      preeclamptic (uterine vein, mean +/- SD: 129 +/- 106 pg/ml vs. antecubital vein,
      mean +/- SD: 82 +/- 43 pg/ml; paired t-tests, p = 0.2) and normal pregnancy
      groups (uterine vein, mean +/- SD: 331 +/- 254 pg/ml vs. antecubital vein, mean
      +/- SD: 319 +/- 259 pg/ml; paired t-tests, p = 0.4). The mean plasma
      concentration of PlGF, either in the uterine or antecubital vein, was lower in
      preeclampsia than in normal pregnancy (unpaired t-tests; p = 0.008 and 0.02
      respectively). CONCLUSIONS: Plasma concentration of sVEGFR-1 was higher in the
      uterine vein than in the antecubital vein in women with preeclampsia. This
      provides evidence supporting the concept that the uterus is a potential source of
      the excess circulating sVEGFR-1 concentration in preeclamptic women.

PMID- 16105788
TI  - Risk factors for intrauterine growth restriction in a socio-economically
      disadvantaged region.
AB  - BACKGROUND: Risk factors for pregnancies being complicated by the birth of a
      small-for-gestational age (SGA) infant were analysed in a socio-economically
      disadvantaged area, with separate analysis for population-based and customized
      based birth weight percentiles. METHODS: A retrospective case-controlled study of
      all singleton pregnancies resulting in the birth of an infant with a birth weight
      < 10 population-based centile, born in the Northern suburbs of metropolitan
      Adelaide, between 1998 and 2003. Significant risk factors in the univariate
      analysis were subsequently checked with multivariate analysis. RESULTS: The
      analyses confirm marked differences between population-based and customized-birth
      weight centiles. Patterns of risk factors show clear differences in risk factors
      for these two different SGA groups. Univariate analyses of all (nulliparous and
      multiparous women) customized SGA infants shows us the following odds ratio's
      (OR); unemployment OR 2.06, 95% confidence interval (CI) 1.46-2.92, being a
      single mother OR 1.90, CI 1.76-2.05, smoking OR 3.24, CI 2.32 - 4.54,
      recreational drug use OR 2.40, CI 1.55-3.70, mental health problems OR 1.52, CI
      1.04-2.23, domestic violence OR 3.42, CI 1.26-9.29, being healthy OR 0.43, CI
      0.30-0.61, preeclampsia OR 1.73, CI 1.01-2.97, and BMI < 30 OR 0.63 CI 0.43-0.93.
      Length of pregnancy interval had no relationship whatsoever with the risk of
      being delivered of an SGA infant. Multivariate analyses for customized SGA showed
      five factors with an OR > 2 (95% CI not crossing 1), including unemployment,
      smoking, maternal age > 34 years, not being healthy and preeclampsia, while
      different paternity, age 25-34 compared to age < 25 were also found to be
      significant risk factors. Higher systolic blood pressure was found to convey
      significant protection. CONCLUSION: When studying risk factors for pregnancies
      complicated by the birth of an SGA infant, both population-derived and customized
      growth centiles should be utilized. This study confirms the importance of smoking
      as a major risk factor, our data also show major protection being conveyed by
      having a regular job and being generally healthy. Pregnancy interval did not have
      any relationship with the birth of SGA infants, while paternity change was
      identified as a clear risk factor. Although genuine preeclampsia persists as a
      clear risk factor, higher systolic blood pressure appears to convey protection.

PMID- 16105787
TI  - Thrombin-dependent regulation of matrix metalloproteinase (MMP)-9 levels in human
      fetal membranes.
AB  - OBJECTIVE: Amniochorion matrix metalloproteinase (MMP)-9 levels increase during
      labor, reaching a maximum in patients with preterm premature rupture of membranes
      (PPROM). Bleeding is a major risk factor for PPROM. Since such hemorrhage into
      the tissue factor-enriched decidua induces intense thrombin formation, we
      determined whether thrombin stimulates MMP levels in amniochorionic membranes.
      STUDY DESIGN: Fetal membrane (amniochorion) cultures were maintained in media
      with and without thrombin, lipopolysaccharide (LPS), thrombin receptor agonist
      peptide (TRAP)-14, and the anti-inflammatory steroid, dexamethasone (DEX).
      Concentrations of MMP-9, MMP-1, and tissue inhibitor of metalloproteinase (TIMP)
      1 in culture media were measured by ELISA and normalized to total cell protein.
      RESULTS: The presence of thrombin induced MMP-9 levels. TRAP-14, a thrombin
      receptor agonist, also significantly increased MMP-9 levels, suggesting that
      thrombin-induced changes in MMP-9 expression were mediated through the thrombin
      receptor. Conversely, levels of MMP-1 and TIMP-1 were not affected by thrombin
      treatment, indicative of specificity of its action. The presence of LPS increased
      the concentration of MMP-9 and MMP-1. In contrast, DEX treatment significantly
      reduced MMP-9 levels. CONCLUSION: Our findings clearly demonstrated that thrombin
      treatment selectively increased the concentration of MMP-9 in culture media of
      amniochorionic membranes. Our results provide a potential mechanism through which
      alterations in hemostasis promote PPROM through thrombin-dependent stimulation of
      MMP-9.

PMID- 16105789
TI  - Idiopathic vaginal bleeding during pregnancy as the only clinical manifestation
      of intrauterine infection.
AB  - OBJECTIVE: To determine the frequency and clinical significance of microbial
      invasion of the amniotic cavity (MIAC) in patients with vaginal bleeding in the
      absence of placenta previa, preterm labor or preterm premature rupture of
      membranes (PROM). STUDY DESIGN: This retrospective cohort study included patients
      who presented with vaginal bleeding between 18 and 35 weeks, and underwent an
      amniocentesis shortly after admission for the assessment of the microbiologic
      status of the amniotic cavity and/or fetal lung maturity. Amniotic fluid was
      cultured for aerobic and anaerobic bacteria, as well as genital mycoplasmas.
      Patients presenting with preterm labor, preterm PROM, placenta previa, overt
      placental abruption, and an intrauterine device in situ were excluded, as well as
      those with local cervical bleeding. MIAC was defined as a positive amniotic fluid
      culture. Analysis was conducted with non-parametric statistics. RESULTS: One
      hundred and fourteen patients met the entry criteria. MIAC was detected in 14% of
      cases (16/114). Patients with vaginal bleeding and a gestational age < 28 weeks
      at the time of amniocentesis had a significantly higher frequency of MIAC than
      those with a gestational age 28 weeks [25% (13/52) vs. 4.8% (3/62), respectively;
      p < 0.01]. Ureaplasma urealyticum was the microorganism most frequently isolated
      from the amniotic fluid. Except for one case admitted at 33 weeks, all patients
      with MIAC had an early preterm delivery 32 weeks. Patients with vaginal bleeding
      and MIAC had a shorter procedure-to-delivery interval than those without MIAC
      [MIAC, median survival 19 days (95% CI 10-27 days) vs. no MIAC, median survival
      50 days (95% CI 37-62 days); p < 0.0001]. Patients with vaginal bleeding and MIAC
      had a significantly lower gestational age at delivery and lower birth weight than
      those with vaginal bleeding and negative amniotic fluid cultures (for gestational
      age, median 25 weeks, range 21-33 weeks vs. median 37 weeks, range 19-42 weeks,
      respectively; p < 0.01, and for birth weight, median 750 grams, range 520-1820
      grams vs. 2800 grams, range 520-4880 grams, respectively; p < 0.01), as well as a
      higher frequency of subsequent preterm PROM [81.3% (13/16) vs. 9.2% (9/98); p <
      0.01]. CONCLUSIONS: MIAC was detected in 14% of patients with 'idiopathic'
      vaginal bleeding and was associated with subsequent preterm PROM and early
      preterm delivery. Vaginal bleeding may be the only clinical manifestation of
      MIAC, and it predisposes to adverse outcome.

PMID- 16105790
TI  - Physical well-being in women with a history of severe preeclampsia.
AB  - OBJECTIVE: To evaluate the physical and mental health of women with a history of
      severe preeclampsia. METHODS: In a historical cohort study 131 former patients
      with a history of severe preeclampsia and 127 control patients received
      questionnaires about experienced physical and mental complaints after delivery.
      At a follow-up visit blood pressure, body mass index, and proteinuria were
      measured and venous blood was drawn. RESULTS: Former patients experienced
      significantly (p < 0.001) more frequent problems of headache (31% vs. 2%), right
      upper quadrant pain (16% vs. 1%), visual disturbances (21% vs. 1%), tiredness
      (66% vs. 27%), subjective loss of concentration (37% vs. 16%), and mental health
      (37% vs. 6%) compared with controls. When present, these health problems, except
      for tiredness, lasted significantly more often beyond six months postpartum
      compared to controls. Admittance to the intensive care unit was associated with
      headache, and subjective loss of memory and concentration over a longer period of
      time. The risk of recurrence of severe preeclampsia was a subject of concern in
      20% of former patients. At follow-up, systolic and diastolic blood pressures were
      significantly higher (p < 0.001) among former patients. CONCLUSION: Patients with
      a history of severe preeclampsia more frequently reported physical and mental
      complaints, also during a longer period of time.

PMID- 16105791
TI  - Efficacy of aggressive tocolysis for preterm labor with advanced cervical
      dilatation.
AB  - OBJECTIVE: Study the effectiveness of tocolysis for preterm labor with advanced
      cervical dilatation ( > or = 3 cm) to achieve sufficient latency for the effect
      of steroids to occur, and delivery of more mature neonates. STUDY DESIGN: We
      studied 249 singleton pregnancies, 23-36 weeks gestation in preterm labor,
      stratified by weeks of gestation and degree of cervical dilatation (Group A: 117,
      < 3 cm; Group B: 132, 3 cm) who were given tocolysis and compared for the length
      of latency and neonatal outcome. RESULTS: Maternal characteristics were similar
      between groups except African-American women were admitted with more advanced
      cervical dilatation. Latency 72 hours was achieved in Group A: > 75% at all
      gestational ages, and Group B: > 50%. Latency > or = 72 hours, according to the
      degree of cervical dilatation, was for Group A: 90%, for Group B: 50-75% from > 3
      5 cm dilatation, and 40% at 5.1-6 cm dilatation. Neonatal morbidity was mild with
      a decreased risk of long-term disability. CONCLUSIONS: Aggressive tocolytic
      therapy for preterm labor with advanced cervical dilatation is efficacious,
      allows for steroid therapy, and allows delivery of more mature neonates.

PMID- 16105792
TI  - The relationship between practice setting and management of preterm premature
      rupture of membranes.
AB  - OBJECTIVE: To compare preterm premature rupture of membranes (PPROM) management
      between maternal-fetal medicine (MFM) providers practicing in an academic
      university (AU) versus other settings (NAU). METHODS: Secondary analysis of a
      national survey of 1375 MFM providers of whom 504 (37%) responded and answered
      queries on demographic and practice characteristics and various PPROM management
      issues. RESULTS: Fifty-three percent of the respondents were in an AU practice
      setting. Providers in AU and NAU settings reported a similar prevalence of
      corticosteroid (99% vs. 100%), antibiotic (99% vs. 100%), and tocolytic (74% vs.
      76%) use. There was significant variability between NAU and AU providers in
      issues related to the evaluation and expectant management of PPROM. NAU
      providers, as compared to AU providers, more commonly reported performing
      diagnostic amniocentesis in the acute evaluation of PPROM (72% vs. 61%, p =
      0.02). There was a higher prevalence of fetal lung maturity assessment among NAU
      providers (84%) as compared to AU providers (73%, p = 0.005) and significant
      variability was noted with respect to the fetal lung maturity tests used (p <
      0.0001). NAU providers continued expectant management later into gestation than
      AU providers (p = 0.002). Significant variability was also noted in the use of
      antepartum surveillance techniques (p = 0.01). CONCLUSION: MFM practitioners from
      academic universities and non-academic settings utilize similar management
      strategies for PPROM in regard to corticosteroid, tocolytic, and antibiotic use.
      However, differences are evident in issues related to the evaluation and
      expectant management of patients with PPROM.

PMID- 16105793
TI  - Comparison of elective induction of labor with favorable Bishop scores versus
      expectant management: a randomized clinical trial.
AB  - OBJECTIVE: To determine if elective induction (IND) increases the risk of
      cesarean delivery compared to expectant management (EM). METHODS: A randomized
      clinical trial involving women 39 weeks' gestation, according to strict dating
      criteria, with a Bishop score of 5 or more in nulliparous patients and 4 or more
      in multiparous patients. The control group was expectantly managed and delivered
      for obstetric indications, but not later than 42 weeks' gestation. The study had
      80% power to detect a three-fold increase in cesarean delivery. RESULTS: One
      hundred-and-sixteen patients (45 nulliparous) were randomized to IND and 110 (58
      nulliparous) to EM. Demographic characteristics were no different between the
      groups. The cesarean delivery rate in the IND group was 6.9% (8/116) compared to
      7.3% (8/110) in the EM group (p = NS). Rates of cesarean delivery for nulliparous
      patients randomized to IND compared to EM were also not significantly different:
      13.3% (6/45) versus 10.3% (6/58) respectively (p = NS). Neonates delivered of IND
      patients weighed less than those of the EM group (3459 +/- 347 versus 3604 +/-
      438, p = 0.006). CONCLUSION: In women with favorable Bishop scores, elective
      induction of labor resulted in no increase in cesarean delivery compared to
      expectant management.

PMID- 16105794
TI  - Frequency of echogenic intracardiac focus by race/ethnicity in euploid fetuses.
AB  - OBJECTIVE: To determine the frequency of echogenic intracardiac focus (EIF) by
      race/ethnicity. METHODS: We performed a retrospective analysis from January 1996
      through June 2003. We reviewed all initial sonograms from 14 to 23 weeks
      gestation in singleton pregnancies. Mothers on admission for delivery provided
      race/ethnicity. RESULTS: There were 8207 ultrasounds and deliveries that met
      study criteria. There were 4636 (56.5%) Caucasian, 2087 (25.4%) African-American,
      1261 (15.4%) Hispanic and 223 (2.7 %) Asian subjects. There were 347 (4.2%) EIF
      detected. The frequency by race/ethnicity varied significantly (p < 0.0001).
      CONCLUSIONS: This large, population-based study showed that fetuses born to Asian
      mothers were significantly more likely to have an EIF. This racial difference
      should be taken into account when counseling patients about the potential for
      Down syndrome.

PMID- 16105795
TI  - Strategies for prevention of feed intolerance in preterm neonates: a systematic
      review.
AB  - Postnatal growth restriction and failure to thrive have been recently identified
      as a major issue in preterm, especially extremely-low-birth-weight neonates. An
      increased length of time to reach full enteral feedings is also significantly
      associated with a poorer mental outcome in preterm neonates at 24 months
      corrected age. Optimization of enteral nutrition without increasing the risk of
      necrotizing enterocolitis (NEC) has thus become a priority in preterm neonates. A
      range of feeding strategies currently exists for preventing/minimizing feed
      intolerance in preterm neonates reflecting the dilemma surrounding the definition
      and significance of signs of feed intolerance due to ileus of prematurity and the
      fear of NEC. The results of a systematic review of current strategies for
      preventing/minimizing feed intolerance in preterm neonates are discussed. The
      need for clinical research in the area of signs of feed intolerance is emphasized
      to develop a scientific basis to feeding strategies. Only large pragmatic trials
      based on such strategies will reveal whether the benefits (improved growth and
      long term neurodevelopmental outcomes) of aggressive enteral nutrition can
      outweigh the risks of a potentially devastating illness like NEC, and of
      prolonged parenteral nutrition in preterm neonates.

PMID- 16105796
TI  - Hyponatremia and preeclampsia.
AB  - A 33-year-old healthy woman, gravida 1 with twins pregnancy was admitted with
      mild preeclampsia and unusual hyponatremia which resolved promptly postpartum.
      This is the seventh reported case of hyponatremia complicating preeclampsia, four
      of the patients carried twins and four had nephrotic syndrome.

PMID- 16105798
TI  - A field study to assess the long-term sampling feasibility of evacuated canisters
      and the development of a mathematical model to analyze potential sampling bias.
AB  - Small, evacuated canisters (300 mL) equipped with a unique capillary flow
      controller were used to evaluate airborne concentrations of Stoddard solvent. The
      physical characteristics of the flow controller permitted the collection of air
      samples for a time period of 40 hours (5 consecutive work days). Long-term
      sampling (greater than 8 hours) is rarely performed in industrial hygiene due to
      limitations in current air sampling technology but may provide valuable
      information in characterizing worker cumulative exposures for some processes. A
      field study was performed to evaluate the feasibility of collecting a 40-hour
      area sample using the small canisters. Six canister samplers were used as area
      monitors to evaluate a cleaning operation for an entire workweek. For comparison,
      30 diffusive badges (6 per day) were simultaneously used to monitor the same
      process. No statistical difference was found between the time-weighted average
      for the two sampling methods (p > 0.05). In addition, the canister samples
      integrate airborne concentrations for an entire workweek and therefore peak
      concentrations are not explicitly observed. Thus, an examination of peak
      exposures using simulated concentrations was conducted. A mathematical model was
      developed to determine whether a significant sampling bias was associated with
      long-term canister sampling when peak concentrations are present. The maximum
      possible bias was determined to be less than 9% for peak amplitudes having 10
      times the background concentration and well below that for smaller amplitudes.
      Long-term sampling with the small, evacuated canisters was found to provide
      results comparable to sorbent sampling methods but with the added benefit of a
      significantly increased sampling time.

PMID- 16105799
TI  - Early pathophysiological features in canine renal papillary necrosis induced by
      nefiracetam.
AB  - To ascertain the early pathophysiological features in canine renal papillary
      necrosis (RPN) caused by the neurotransmission enhancer nefiracetam, male beagle
      dogs were orally administered nefiracetam at 300 mg/kg/day for 4 to 7 weeks in
      comparison with ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), at 50
      mg/kg/day for 5 weeks. During the dosing period, the animals were periodically
      subjected to laboratory tests, light-microscopic, immunohistochemical, and
      electron-microscopic examinations and/or cyclooxygenase (COX)-2 mRNA analysis. In
      laboratory tests, a decrease in urinary osmotic pressure and increases in urine
      volume and urinary lactate dehydrogenase (LDH) level were early biomarkers for
      detecting RPN. Light-microscopically, nefiracetam revealed epithelial swelling
      and degeneration in the papillary ducts in week 7, while ibuprofen displayed
      degeneration and necrosis in the papillary interstitium in week 5. In
      immunohistochemical staining with COX-2 antibody, nefiracetam elicited a positive
      reaction within interstitial cells around the affected epithelial cells in the
      papillary ducts (upper papilla) in week 7, and ibuprofen positively reacted
      within interstitial cells adjacent to the degenerative and/or necrotic lesions in
      week 5. Ultrastructurally, nefiracetam exhibited reductions of intracellular
      interdigitation and infoldings of epithelial cells in the papillary ducts,
      whereas ibuprofen showed no changes in the identical portions. Thus, the early
      morphological change in the papilla brought about by nefiracetam was quite
      different from that elicited by ibuprofen. By the renal papillary COX-2 mRNA
      expression analysis, nefiracetam exceedingly decreased its expression in week 4,
      but markedly increased it in week 7, suggesting an induction of COX-2 mRNA by
      renal papillary lesions. These results demonstrate that the epithelial cell in
      the papillary ducts is the primary target site for the onset of RPN evoked by
      nefiracetam.

PMID- 16105800
TI  - Brainstem axonal degeneration in mice with deletion of selenoprotein p.
AB  - Selenoprotein P is an abundant extracellular protein that is expressed in liver,
      brain, and other tissues. Studies in mice with the selenoprotein P gene deleted
      (Sepp-/- mice) have implicated the protein in maintaining brain selenium. Sepp-/-
      mice fed a normal or low selenium diet develop severe motor impairment and die,
      but Sepp-/- mice fed a high selenium diet remain clinically unimpaired. As an
      initial step to evaluate the effect of selenoprotein P deletion on central
      nervous system architecture, the brains and cervical spinal cords of Sepp-/- and
      Sepp+/+ mice fed low or high selenium diets were examined by light and electron
      microscopy. Brains of Sepp-/- mice demonstrated no gross abnormalities. At the
      light microscopic level, however, Sepp-/- mice fed either the selenium deficient
      diet or the high selenium diet had enlarged dystrophic axons and degenerated
      axons in their brainstems and cervical spinal cords. No axonal lesions were
      observed in the Sepp+/+ mice fed either diet. Electron microscopy demonstrated
      that the enlarged axons in the Sepp-/- mice were packed with organelles,
      suggesting a deficit in fast axonal transport. The similar severity of axonal
      lesions observed in Sepp-/- mice fed the 2 diets suggests that axonal dystrophy
      is a common phenotype for deletion of selenoprotein P regardless of selenium
      intake and that additional studies will be required to determine the pathogenesis
      of the neurological signs and mortality observed in Sepp-/- mice fed a low
      selenium diet.

PMID- 16105801
TI  - Selected extraskeletal effects of systemic treatment with basic fibroblast growth
      factor in ovariectomized rats.
AB  - Basic fibroblast growth factor (bFGF) is a pleiotropic mitogen with a potent bone
      forming effect, rendering it a potential osteoporosis therapy. This study
      examined selected extraskeletal effects of bFGF in ovariectomized rats, a well
      established model of human postmenopausal osteopenia, to more fully characterize
      side effects associated with bFGF treatment. Five-month-old, osteopenic,
      ovariectomized rats were injected subcutaneously with vehicle or bFGF (1 mg/kg)
      daily for 3 weeks. Hematologic and biochemical analyses were performed; and
      kidneys, livers, and proximal tibiae were examined histologically and
      histomorphometrically. bFGF administration resulted in anemia that was due to a
      shift toward granulocyte production in the bone marrow. Increased granulocyte
      production was also observed in the liver of bFGF-treated rats, which exhibited a
      markedly increased number and area of hematopoietic foci. bFGF administration
      also caused mild glomerular hypertrophy that was not attended by significant
      biochemical evidence of glomerular dysfunction. The bone anabolic effect of
      subcutaneous bFGF administration was confirmed in the proximal tibia, and was
      associated with a significant decrease in urine fractional excretion of calcium
      in bFGF-treated rats. Though bFGF strongly stimulates bone formation at
      osteopenic skeletal sites, its extraskeletal effects may restrict the long-term
      use of bFGF in its current form as an osteoporosis therapy.

PMID- 16105802
TI  - Estimating leaf-level parameters for ecosystem process models: a study in mixed
      conifer canopies on complex terrain.
AB  - Ecosystem process models are often used to predict carbon flux on a landscape or
      on a global scale. Such models must be aggregate and canopies are often treated
      as a uniform unit of foliage. Parameters that are known to vary within the
      canopy, e.g., nitrogen content and leaf mass per area, are often estimated by a
      mean value for the canopy. Estimating appropriate means is complicated,
      especially in mixed-species stands and in complex terrain. We analyzed sources of
      variation in specific parameters with the goal of testing various simplifying
      assumptions. The measurements came from mixed-species forests in the northern
      Rocky Mountains. We found that, for three important parameters (nitrogen
      concentration and content, and leaf mass per area), a sample taken near the
      vertical center of the crown provided a good estimate of the mean values for the
      crown. Altitude (700-1700 m), solar insolation (4200-5400 MJ m(-2) year(-1)) and
      leaf area index (1-11) had negligible effects on the parameters; only species
      differences were consistently detected. The correlation between mass-based
      photosynthetic rates and mass-based nitrogen concentrations was much weaker than
      the correlation between area-based photosynthetic rates and area-based nitrogen
      concentration. Comparison of photosynthesis-nitrogen relationships for a wide
      variety of conifer species and sites revealed a broad general trend that can be
      used in models. These results suggest important potential simplifications in
      model parameterization, most notably that canopy means can be estimated with
      ease, that complex terrain is a minor source of variation in these parameters and
      that use of one photosynthesis-nitrogen relationship for conifer species does not
      result in large errors. Species-to-species variation, however, was large and
      needs to be accounted for when parameterizing process models.

PMID- 16105803
TI  - Induction and differential expression of beta-1,3-glucanase mRNAs in tolerant and
      susceptible Hevea clones in response to infection by Phytophthora meadii.
AB  - Most cultivated rubber tree (Hevea brasiliensis Willd. ex A. Juss.) clones in
      India are susceptible to abnormal leaf fall disease (ALF), which is caused by
      various Phytophthora species and results in yield losses of up to 40%. Because
      the conventional breeding programs for this perennial tree crop are complex and
      time consuming, we attempted to find a molecular solution to increase the
      tolerance of rubber trees to ALF. The expression patterns of the gene coding for
      the pathogenesis-related beta-1,3-glucanase (beta-glu) enzyme in a tolerant (RRII
      105) and a highly susceptible (RRIM 600) clone of rubber tree were examined,
      following infection with ALF-causing Phytophthora meadii McRae. Infected leaf
      samples were collected at different times after inoculation, and RNA was
      extracted and subjected to Northern blot hybridization and reverse transcriptase
      polymerase chain reaction (RT-PCR). On hybridization with a 1.25 kb beta-glu
      probe, Northern blots showed a marked increase in beta-glu transcript levels in
      both clones 48 h after inoculation. However, compared with the susceptible RRIM
      600 clone, the tolerant RRII 105 clone had a higher rate of increase and a more
      prolonged induction, with beta-glu transcript levels remaining high for 4 days
      after inoculation. In RRIM 600, the mRNA levels decreased significantly 48 h
      after inoculation. On re-hybridization with an 18S rRNA probe, uniform signals
      were detected in all the lanes, indicating that an equal amount of total RNA was
      present in all samples. Similar results were obtained in relative quantitative RT
      PCR experiments with the housekeeping actin gene as an internal control. Thus,
      although induction of the beta-glu gene occurred in both tolerant and susceptible
      clones, the predominant difference between clones was in the intensity and
      duration of the response. The tolerance of clone RRII 105 may be associated with
      the prolonged expression of the gene following infection. The antifungal activity
      of these hydrolase enzymes makes them rational candidates for overexpression by
      genetic transformation to produce disease resistant crops.

PMID- 16105804
TI  - Does rainfall explain variation in leaf morphology and physiology among
      populations of red ironbark (Eucalyptus sideroxylon subsp. tricarpa) grown in a
      common garden?
AB  - We investigated adaptation of leaf morphology and physiology of red ironbark
      (Eucalyptus sideroxylon Cunn. Ex. Wools subsp. tricarpa L.A.S. Johnson) in a
      common garden experiment. Fifteen populations, representing a rainfall range of
      500 to 1055 mm per annum at the sites of seed collection, were grown at the same
      site. Because environmental variables other than rainfall did not vary
      significantly among populations, we were able to test if leaf morphology and
      physiology were related to seed-source rainfall. There were large differences
      among and within populations in all measured variables. Most univariate
      relationships with seed-source rainfall were not significant. Notable exceptions
      were the weak positive correlation of specific leaf area with seed-source
      rainfall-consistent with expectations-and the weak negative correlation of
      photosynthesis and stomatal conductance with seed-source rainfall-the opposite of
      what we predicted. In many cases, populations collected from sites of similar
      rainfall differed greatly in leaf morphology and physiology. Principal component
      analysis (PCA) reduced the 13 input variables to five principal components (PC)
      explaining 73.0% of the total variance in the original data. Some of the PC axes
      could be interpreted in terms of adaptation to drought (i.e., to seed-source
      rainfall), but relationships of accumulated variables (the PC axes) with seed
      source rainfall were significant for only one PC axis. Hence, among red ironbark
      populations grown in a common garden, there was significant genetic variation in
      leaf morphology and physiology, but for most traits, this variation was unrelated
      to rainfall at the site of seed collection. This study adds to a growing body of
      common garden literature showing weak within-species relationships of leaf
      morphology and physiology with seed-source rainfall, in contrast to the
      consistently stronger relationships among species growing at different points
      along broad environmental gradients.

PMID- 16105805
TI  - Refugial forests of the southern Appalachians: photosynthesis and survival in
      current-year Abies fraseri seedlings.
AB  - Fraser fir (Abies fraseri (Pursh) Poiret) is an endemic, high-elevation conifer
      confined to six relict mountaintop communities in the southern Appalachian
      Mountains, USA. High adult mortality has occurred over the past 50 years,
      possibly the result of an introduced insect (Adelges piceae Ratzeburg), air
      pollution, or both. Knowledge of the mechanisms of and limitations to seedling
      establishment may allow reestablisment and perpetuation of this unique community
      type, notwithstanding global climate change. We monitored seedling emergence and
      mortality in relation to photosynthetic performance and water relations in
      microsites differing in canopy openness (sunlight exposure) over the summer of
      2004. Abundance of cotyledonous seedlings in early summer was 2.3 times greater
      (849 versus 366 seedlings m(-2)) in microsites with lower sky exposure (greater
      canopy closure) than in microsites with greater sky exposure (greater canopy
      openness). In contrast, late-season abundance and survival were greater in areas
      beneath more open canopies than in areas beneath less open canopies (3.3 times
      and 11.7 times greater, respectively). However, newly emerged seedling survival
      in a completely open site (no overhead canopy) was zero, despite an initial
      density of 124 seedlings m(-2). Seedling water status was similar in open- and
      closed-canopy sites (-0.52 and -0.74 MPa, respectively). Photosynthetic carbon
      gain was higher in newly emerged seedlings at open canopy than at closed canopy
      sites, especially during early morning. Based on photosynthetic light response
      curves and measured sunlight regimes, seedlings in open canopy sites were
      estimated to assimilate 3.3-4.5 times more carbon than seedlings at closed sites.
      Reductions in carbon gain of closed-site seedlings, primarily a result of limited
      sunlight, corresponded to substantial increases in seedling mortality (98 versus
      79% in open canopy sites). Thus, sunlight exposure, which reflects overstory
      canopy structure, appears to be an important factor influencing newly emerged
      seedling survival and distribution.

PMID- 16105806
TI  - Low temperature responses of Nothofagus dombeyi and Nothofagus nitida, two
      evergreen species from south central Chile.
AB  - Nothofagus dombeyi (Mirb.) Blume and Nothofagus nitida (Phil.) Krasser are
      closely related evergreen trees native to south central Chile. Nothofagus dombeyi
      is a pioneer in habitats subject to high daytime irradiances and nighttime
      freezing temperatures and has a wider altitudinal and latitudinal distribution
      than N. nitida, which is restricted to more oceanic climates. We postulated that
      N. dombeyi has a greater cold-acclimation capacity, expressed as a greater
      capacity to maintain a functional photosynthetic apparatus at low temperatures,
      than N. nitida. Because cold-acclimation may be related to the accumulation of
      cryoprotective substances, we investigated relationships between ice nucleation
      temperature (IN), freezing temperature (FT), and the temperature causing injury
      to 50% of the leaf tissues (LT(50)) on the one hand, and concentrations of total
      soluble carbohydrates (TSC), starch and proline on the other hand. Observations
      were made throughout a seasonal cycle in adults and seedlings in the field and in
      seedlings in the laboratory under cold-acclimation inductive and non-inductive
      conditions. In adults, LT(50) values were lower in N. dombeyi than in N. nitida,
      suggesting that N. dombeyi is the more frost tolerant species. Adults of both
      species tolerated freezing in autumn and winter but not in spring and summer. In
      the fall and winter, seedlings of N. dombeyi had a much lower LT(50) than those
      of N. nitida. Nothofagus nitida seedlings, in autumn and winter, exhibited
      freezing avoidance mechanisms. Although elevated TSC and proline concentrations
      may contribute to freezing tolerance in adults of both species, an increase in
      proline concentration is unlikely to be the dominant frost tolerance response in
      adults because proline concentrations were higher in N. nitida than in N.
      dombeyi. In seedlings, however, there were large differences in proline
      accumulation between species that may account for the difference between them in
      freezing tolerance. Starch concentration in both species decreased during winter.
      Chlorophyll fluorescence indicated that maximal photochemical efficiency
      (F(v)/F(m)) remained at optimal values (~0.8) throughout the year. The effective
      photochemical efficiency of PSII (PhiPSII) and relative electron transport rates
      (ETR(r)) decreased in winter in both species. In seedlings, fluorescence
      parameters were more affected in winter in N. nitida than in N. dombeyi. We
      concluded that adults and seedlings of N. dombeyi are hardier than adults and
      seedlings of N. nitida, which is consistent with its wider latitudinal and
      altitudinal distribution.

PMID- 16105807
TI  - Net carbon storage in a poplar plantation (POPFACE) after three years of free-air
      CO2 enrichment.
AB  - A high-density plantation of three genotypes of Populus was exposed to an
      elevated concentration of carbon dioxide ([CO(2)]; 550 micromol mol(-1)) from
      planting through canopy closure using a free-air CO(2) enrichment (FACE)
      technique. The FACE treatment stimulated gross primary productivity by 22 and 11%
      in the second and third years, respectively. Partitioning of extra carbon (C)
      among C pools of different turnover rates is of critical interest; thus, we
      calculated net ecosystem productivity (NEP) to determine whether elevated
      atmospheric [CO(2)] will enhance net plantation C storage capacity. Free-air
      CO(2) enrichment increased net primary productivity (NPP) of all genotypes by 21%
      in the second year and by 26% in the third year, mainly because of an increase in
      the size of C pools with relatively slow turnover rates (i.e., wood). In all
      genotypes in the FACE treatment, more new soil C was added to the total soil C
      pool compared with the control treatment. However, more old soil C loss was
      observed in the FACE treatment compared with the control treatment, possibly due
      to a priming effect from newly incorporated root litter. FACE did not
      significantly increase NEP, probably as a result of this priming effect.

PMID- 16105808
TI  - Leaf hydraulic conductance in relation to anatomical and functional traits during
      Populus tremula leaf ontogeny.
AB  - Leaf hydraulic conductance (K(leaf)) and several characteristics of hydraulic
      architecture and physiology were measured during the first 10 weeks of leaf
      ontogeny in Populus tremula L. saplings growing under control, mild water deficit
      or elevated temperature conditions. During the initial 3 weeks of leaf ontogeny,
      most measured characteristics rapidly increased. Thereafter, a gradual decrease
      in K(leaf) was correlated with a decrease in leaf osmotic potential under all
      conditions, and with increases in leaf dry mass per area and bulk modulus of
      elasticity under mild water deficit and control conditions. From about Week 3
      onward, K(leaf) was 33% lower in trees subjected to mild water deficit and 33%
      higher in trees held at an elevated temperature relative to control trees. Mild
      water deficit and elevated temperature treatment had significant and opposite
      effects on most of the other characteristics measured. The ontogenetic maximum in
      K(leaf) was correlated positively with the width of xylem conduits in the midrib,
      but negatively with the overall width of the midrib xylem, number of lateral
      ribs, leaf dry mass per area and bulk modulus of elasticity. The ontogenetic
      maximum in K(leaf) was also correlated positively with the proportion of
      intercellular spaces and leaf osmotic potential, but negatively with leaf
      thickness, volume of mesophyll cells and epidermis and number of cells per total
      mesophyll cell volume, the closest relationships being between leaf osmotic
      potential and number of cells per total mesophyll cell volume. It was concluded
      that differences in protoplast traits are more important than differences in
      xylem or parenchymal cell wall traits in determining the variability in K(leaf)
      among leaves growing under different environmental conditions.

PMID- 16105809
TI  - Differentiation and functional connection of vascular elements in compatible and
      incompatible pear/quince internode micrografts.
AB  - Micrografts of internodes excised from in vitro grown pear plants (Pyrus communis
      L. cv. 'Bosc' (B) and cv. 'Butirra Hardy' (BH)) and quince (Cydonia oblonga Mill.
      East Malling clone C (EMC)), were cultured aseptically to test the effectiveness
      of their functional vascular reconnection in relation to incompatibility
      compatibility relationships that these genotypes exhibit in the field. The
      incompatible heterograft (B/EMC) showed a marked delay in internode cohesion
      compared with the autografts (both B/B and BH/BH) and the compatible heterograft
      (BH/EMC). Even when fused, the translocation of [14C]-sorbitol from upper to
      lower internode was lower in B/EMC micrografts than in the other combinations.
      Epifluorescence studies performed with carboxyfluorescin, a specific phloem
      probe, indicated that the limited translocation was caused by a delay in the
      establishment of functional phloem continuity between the two internodes. In the
      B/EMC combination, new differentiated tracheary elements (TE) in the parenchyma
      tissue at the graft interface between the two internodes were not detected until
      30 days after grafting, whereas in the BH/EMC heterograft and both autografts,
      new xylem connections appeared to cross the interface 20 days after grafting.
      Immunohistochemical detection (terminal nick-end labeling assay) of the number of
      cells undergoing nuclear DNA fragmentation at the graft interface confirmed that
      the limited and delayed TE differentiation in B/EMC heterografts was associated
      with a decrease in the activity of programmed cell death processes involved in
      the differentiation of TE.

PMID- 16105810
TI  - Spatial and temporal variations in soil respiration in relation to stand
      structure and soil parameters in an unmanaged beech forest.
AB  - Soil CO2 efflux (soil respiration) plays a crucial role in the global carbon
      cycle and efflux rates may be strongly altered by climate change. We investigated
      the spatial patterns of soil respiration rates in 144 measurement locations in a
      0.5-ha plot and the temporal patterns along a 300-m transect in the 0.5-ha plot.
      Measurements were made in an unmanaged, highly heterogeneous beech forest during
      2000 and 2001. We investigated the effects of soil, roots and forest stand
      structure on soil respiration, and we also assessed the stability of these
      spatial patterns over time. Soil temperature alone explained between 68 and 95%
      of the temporal variation in soil respiration; however, pronounced spatial
      scatter of respiration rates was not explained by soil temperature. The observed
      spatial patterns stayed remarkably stable throughout the growing season and over
      2 years. The most important structural parameter of the stand was the mean
      diameter at breast height of trees within a distance of 4 m of the measurement
      locations (m-dbh4), which explained 10-19% of the variation in soil respiration
      throughout the growing season. Among the soil chemical parameters, carbon content
      (bulk as well as dissolved) and magnesium content explained 62% of the spatial
      variation in soil respiration. The final best model combining soil, root and
      stand structural parameters (fine root biomass, soil carbon content, m-dbh4 and
      soil water content) explained 79% of the variation in soil respiration,
      illustrating the importance of both biotic and abiotic factors.

PMID- 16105811
TI  - Impact of fertilization on tree-ring delta15N and delta13C in beech stands: a
      retrospective analysis.
AB  - We studied the effects of two fertilization treatments (N and NPKCa) on wood
      nitrogen (N) isotope composition (delta(15)N), water-use efficiency (WUE)
      estimated by carbon isotope composition (delta(13)C) analyses, and ring width of
      trees in 80-year-old beech (Fagus sylvatica L.) stands in the forest of Fougeres,
      western France. Four replicates were fertilized in two successive years (1973 and
      1974), 20 years before core sampling. Unfertilized control trees displayed a
      decreasing delta(15)N trend with time. The N and NPKCa treatments both increased
      delta(15)N compared with the control treatment. Wood extraction by organic
      solvents enhanced the delta(15)N signal. Thus, N addition to the beech ecosystem,
      even in moderate amounts, could be traced back in tree-ring delta(15)N,
      suggesting that wood N isotope analysis is a promising tool for studying the long
      term effects of N deposition on forests. Although WUE decreased for about 6 years
      after N fertilization, WUE in NPKCa-treated trees did not differ significantly
      from that in control trees. Results were similar whether based on cellulose or
      total wood delta(13)C analysis, suggesting that extraction of cellulose is not
      necessary when studying fertilization impacts on WUE. The NPKCa treatment had a
      large impact on radial growth, causing a significant long-lasting increase of 29%
      compared with the control treatment. Nitrogen alone did not change radial growth
      significantly.

PMID- 16105812
TI  - Root temperature drives winter acclimation of shoot water relations in
      Cryptomeria japonica seedlings.
AB  - In many temperate evergreen plant species, reductions in turgor loss point of
      leaves (Psi(tlp)) and leaf osmotic potential at full turgor (pi(sat)) occur from
      late summer to winter. To test the hypothesis that this seasonal change in leaf
      water relations is driven by root temperature, we manipulated the temperature of
      the roots and shoots of Cryptomeria japonica D. Don seedlings separately. Whole
      plant warming diminished the seasonal changes in shoot water relations observed
      in the control plants, whereas shoot warming did not. Compared with the controls,
      root warming diminished the change in Psi(tlp) but not in pi(sat), whereas
      cooling accelerated the seasonal changes in shoot water relations. These results
      indicate that: (1) temperature responses of roots are involved in the seasonal
      changes in Psi(tlp) from late summer to winter; and (2) root temperature is
      partly responsible for the simultaneous changes in pi(sat). Whole-plant cooling
      caused increased root hydraulic resistance, suggesting that seasonal changes in
      shoot water relations represent adaptive responses to increased root hydraulic
      resistance at low root temperatures.

PMID- 16105813
TI  - Selection strategy for a seedling seed orchard design based on trait selection
      index and genomic analysis by molecular markers: a case study for Eucalyptus
      dunnii.
AB  - Molecular genetic analysis was applied to 162 individuals of 37 half-sib selected
      families belonging to six provenances of Eucalyptus dunnii Maiden in a
      provenance/family trial. The individuals were selected by a trait selection index
      and genetic diversity criteria were later applied for designing seedling seed
      orchards. Genetic diversity and its distribution, as well as relationships among
      individuals, were assessed on the basis of nine microsatellite loci and 243
      amplified fragment length polymorphism markers. High diversity was found with
      both kinds of markers. Clear-cut genomic patterns of identification
      (fingerprinting) were obtained for each individual. Genetic differentiation
      estimates consistently showed low differentiation among provenances (R(ST1) =
      0.069, theta(P) = 0.026 and F(CT) = 0.035) and great differentiation among
      families (R(ST2) = 0.223, theta(S) = 0.174 and F(SC) = 0.164). A high proportion
      of the total variation was observed within families (around 80% by both marker
      analyses), suggesting that orchard design should be based on individual or family
      selection rather than on provenance selection, and that individual ranking by
      both trait selection index and molecular genetic diversity criteria should be
      considered. A selection procedure for a seedling seed orchard design is proposed.

PMID- 16105814
TI  - Daily transpiration rates of woody species on drying soil.
AB  - Among annual plants, daily transpiration rates, expressed as a fraction of
      volumetric soil water content available for transpiration, show a common pattern
      in response to soil drying. Initially, as soil dries, there is little decrease in
      transpiration rate until water availability has fallen to about one third that at
      field capacity. With further soil drying, relative transpiration rate decreases
      in a more-or-less linear fashion until all available water has been used. Data
      previously obtained for perennial woody species have often been confounded by
      different methods for determining available soil water. In this study, we
      investigated the daily transpiration response to soil drying in five woody
      perennial species: Thuja plicata Donn ex D. Don, Acer rubrum L., Robinia
      pseudoacacia L., Hibiscus sp. and Ibex aquifolium L. Transpiration was unaffected
      by soil drying until the initial estimated transpirable soil water fraction had
      decreased to between 0.23 and 0.32 of that at field capacity. Beyond this point,
      transpiration rate declined linearly with available soil water fraction until
      reaching one fifth the rate observed in well-watered plants. With further soil
      drying, the relative transpiration rates remained between 10 and 20% of that
      observed in well-watered plants. Maintenance of transpiration at these rates with
      further soil drying was hypothesized to result from contributions to
      transpiration of water stored in plant tissues. After taking tissue water storage
      into account, it was estimated that transpiration was curtailed as the available
      soil water fraction fell to between 0.26 and 0.37 of that at field capacity,
      which is comparable to values reported for annual crop plants.

PMID- 16105815
TI  - Propofol ensures a more stable A-line ARX index than thiopental during
      intubation.
AB  - BACKGROUND: The A-line autoregressive modelling with exogenous input index (AAI)
      is a new method of assessing depth of anesthesia. We examined the effects of
      tracheal intubation on the AAI and hemodynamics during induction of anesthesia
      with propofol compared with thiopental in patients aged over 50 yr. METHODS: 40
      patients scheduled for a laminectomy, posterior spinal fusion, vertebroplasty, or
      total hip replacement, ASA physical status I or II and aged over 50 yr, were
      randomly divided into two groups. Thiopental 5 mg.kg(-1) iv, fentanyl 2.5
      microg.kg(-1) iv, and rocuronium 0.7 mg.kg(-1) iv were used in the thiopental
      group (n = 20) for anesthetic induction; the same protocol was used in the
      propofol group (n = 20) except that 2 mg.kg(-1) propofol iv was given instead of
      thiopental. The AAI, non-invasive blood pressure, and heart rate were measured
      every minute before induction for three minutes, at 1.5 min post-induction, and
      then each minute post-intubation for eight minutes. RESULTS: The AAI increased
      significantly at one and two minutes after intubation in the thiopental group (to
      56.5 +/- 18.6 at 1 min and 44.7 +/- 18.7 at 2 min after intubation vs 19.9 +/-
      7.5 at 1.5 min after induction; P < 0.05). Thereafter, AAI values gradually
      decreased three minutes after intubation. The AAI was inhibited continuously
      after intubation in the propofol group, and no significant elevation was seen.
      CONCLUSION: Our results, using the AAI to monitor anesthetic depth during
      induction and tracheal intubation, suggest that at equipotent doses propofol
      provided a more stable level of anesthesia than did thiopental.

PMID- 16105816
TI  - Genetic heterogeneity of the epidermal growth factor receptor in non-small cell
      lung cancer cell lines revealed by a rapid and sensitive detection system, the
      peptide nucleic acid-locked nucleic acid PCR clamp.
AB  - Lung cancer is one of the leading causes of the cancer death worldwide. Gefitinib
      is an inhibitor of the tyrosine kinase activity of the epidermal growth factor
      receptor (EGFR) and has been introduced in the treatment of advanced lung
      cancers. The responsiveness to gefitinib has been linked to the presence of EGFR
      mutations. Clinical samples contain many normal cells in addition to cancer
      cells. A method capable of detecting EGFR mutations in a large background of wild
      type EGFR genes could provide a superior clinical test. We developed a rapid and
      sensitive detection system for EGFR mutations named the peptide nucleic acid
      locked nucleic acid (PNA-LNA) PCR clamp that can detect EGFR mutations in the
      presence of 100-to 1,000-fold background of wild-type EGFR. We used this method
      to screen 30 non-small cell lung cancer cell lines established from Japanese
      patients. In addition to 11 cell lines that have mutations, we found 12 cell
      lines in which specific mutations are observed only in the subpopulation(s) of
      the cells. Genetic heterogeneity of EGFR suggests that the EGFR gene is unstable
      in established cancers and the heterogeneity may explain variable clinical
      responses of lung cancers to gefitinib.

PMID- 16105817
TI  - MDs call for socially responsible investments.

PMID- 16105818
TI  - Physiology in perspective: The Wisdom of the Body. Neural control of the kidney.
AB  - Cannon equated the fluid matrix of the body with Bernard's concept of the
      internal environment and emphasized the importance of "the safe-guarding of an
      effective fluid matrix." He further emphasized the important role of the
      autonomic nervous system in the establishment and maintenance of homeostasis in
      the internal environment. This year's Cannon Lecture discusses the important role
      of the renal sympathetic nerves to regulate various aspects of overall renal
      function and to serve as one of the major "self-regulatory agencies which operate
      to preserve the constancy of the fluid matrix."

PMID- 16105819
TI  - Genetic manipulation of 11beta-hydroxysteroid dehydrogenases in mice.
AB  - 11beta-hydroxysteroid dehydrogenases (HSDs) interconvert active 11-hydroxy
      glucocorticoids (cortisol, corticosterone) and their inert 11-keto derivatives
      (cortisone, 11-dehydrocorticosterone). 11beta-HSD type 1 is a predominant
      reductase that regenerates active glucocorticoids in expressing cells, thus
      amplifying local glucocorticoid action, whereas 11beta-HSD type 2 catalyzes rapid
      dehydrogenation, potently inactivating intracellular glucocorticoids. Both
      isozymes thus regulate receptor activation by substrate availability. Spatial and
      temporal regulation of expression are important determinants of the physiological
      roles of 11beta-HSDs, with each isozyme exhibiting a distinct, tissue-restricted
      pattern together with dynamic regulation during development and in response to
      environmental challenges, including diet and stress. Transgenic approaches in the
      mouse have contributed significantly toward an understanding of the importance of
      these prereceptor regulatory mechanisms on corticosteroid receptor activity and
      have highlighted its potential relevance to human health and disease. Here we
      discuss current ideas of the physiological roles of 11beta-HSDs, with emphasis on
      the key contributions made by studies of 11beta-HSD gene manipulation in vivo.

PMID- 16105820
TI  - Integration in the PVN: another piece of the puzzle.

PMID- 16105821
TI  - Antihypertensive and cognitive effects of grape polyphenols in estrogen-depleted,
      female, spontaneously hypertensive rats.
AB  - Both endogenous and dietary estrogens reduce hypertension and enhance cognitive
      abilities in estrogen-depleted female spontaneously hypertensive rats (SHR). Many
      of the beneficial effects of estrogens/phytoestrogens also appear to be provided
      by other polyphenols (e.g., proanthocyanidins) in grape seed, which lack
      appreciable estrogenic receptor binding. The present study tested the hypothesis
      that similar to phytoestrogens, proanthrocyanidins in grape seed polyphenols
      reduce salt-sensitive hypertension in young, estrogen-depleted SHR. SHR were
      ovariectomized at 4 wk of age and placed on phytoestrogen-free diets with or
      without 0.5% grape seed extract added and with high (8.0%) or basal (0.6%) NaCl.
      After 10 wk on the diets, grape proanthrocyanidin supplementation significantly
      reduced arterial pressure in the rats fed the basal (10 mmHg) and high (26 mmHg)
      NaCl diet, compared with the nonsupplemented controls. In vitro superoxide
      production was significantly reduced (23%) by the grape seed polyphenols. Spatial
      learning (8-arm-radial maze) in the SHR on the basal NaCl diets was improved by
      dietary grape seed polyphenols. These results indicate that grape seed
      polyphenols decrease arterial pressure in SHR, probably via an antioxidant
      mechanism.

PMID- 16105822
TI  - Possible neural mediation of the central effects of oxytocin on uterine motility.
AB  - The central nervous system contains the nuclei at the origin of autonomic and
      neuroendocrine pathways to the uterus. Although the anatomical basis of these
      pathways is known, the conditions of their recruitment and their interactions in
      the context of copulation remain to be explored. We tested the hypothesis that
      some central mechanisms could simultaneously recruit both pathways to the uterus.
      In this aim, we recorded intrauterine pressure changes in anesthetized female
      rats at the estrus stage after intracerebroventricular (ICV) administration of
      oxytocin (OT). Doses of 0.3-300 ng elicited increases of frequency and amplitude
      of uterine contractions. These effects were partly mimicked by the OT agonist
      [Thr(4),Gly(7)]OT but not by arginine vasopressin. They were blocked by the OT
      receptor antagonist atosiban delivered either ICV or intravenously. The latter
      suggests that ICV OT activated the systemic release of OT. The effects of OT were
      also blocked by hexamethonium, a ganglionic blocking agent, by atropine, a
      muscarinic receptor antagonist, and by N(omega)-nitro-L-arginine methyl ester, an
      inhibitor of nitric oxide synthesis. The results reveal that ICV OT recruits
      autonomic efferent pathways to the uterus. These results support our hypothesis
      that the activation of central nuclei can promote uterine contractility, and that
      OT may be a central coordinator of autonomic and neuroendocrine pathways. The
      hypothalamus, the source of direct OT-ergic projections to the pituitary, the
      brain stem, and the spinal cord, may be a target of central OT.

PMID- 16105823
TI  - Applying physicochemical principles to skeletal muscle acid-base status.

PMID- 16105824
TI  - Lactate accumulation, proton buffering, and pH change in ischemically exercising
      muscle.

PMID- 16105825
TI  - Lactic acid still remains the real cause of exercise-induced metabolic acidosis.

PMID- 16105827
TI  - Hypothalamic KiSS-1: the missing link in gonadotropin feedback control?

PMID- 16105828
TI  - Tweaking the glucose sensor: adjusting glucokinase activity with activator
      compounds.

PMID- 16105829
TI  - Possible contribution of neonatal ligand-independent activation of estradiol
      receptors to male-typical sexual differentiation of brain and behavior.

PMID- 16105831
TI  - The translational efficiencies of the two Leishmania infantum HSP70 mRNAs,
      differing in their 3'-untranslated regions, are affected by shifts in the
      temperature of growth through different mechanisms.
AB  - Exposure of Leishmania promastigotes to the temperature of their mammalian hosts
      induces a typical heat-shock response. In Leishmania infantum, HSP70 is encoded
      by two types of genes that differ in their 3'-untranslated regions (3'-UTRs).
      Previously, we have shown that specific transcripts for each gene are present in
      promastigotes growing at normal temperature (26 degrees C), but only transcripts
      with 3'-UTR-type I (3'-UTRI) accumulate in a temperature-dependent manner. Here,
      we have investigated the translational efficiencies of both types of HSP70
      transcripts at the different temperatures that the parasite encounters in the
      insect (26 degrees C, normal temperature) or in the mammalian host (heat-shock
      temperatures). Interestingly, 3'-UTRI-bearing transcripts (HSP70-I) were found
      associated with ribosomes in promastigotes at normal and heat-shock temperatures,
      whereas the HSP70-II transcripts appear to be preferentially translated at heat
      shock temperatures but not at 26 degrees C. We have analyzed the function of
      these UTRs in the translational control by use of plasmid constructs in which the
      CAT reporter gene was flanked by UTRs of the HSP70 genes. Unexpectedly, it was
      found that CAT transcripts with 3'-UTRII bind to ribosomes at 26 degrees C, and,
      indeed, the CAT protein is synthesized. A valid conclusion of these experiments
      was that both types of 3'-UTRs are essential for translation of HSP70 mRNAs at
      heat shock temperatures, although the 3'-UTRII is more efficient during severe
      heat shock (39 degrees C). In addition, these results suggest that sequence
      region other than the 3'-UTR of HSP70-II gene is involved in the translational
      silent state of HSP70-II transcripts at 26 degrees C. Finally, a null mutant has
      been created by targeted disruption of both HSP70-II alleles. Remarkably, the
      deltaHSP70 mutant synthesizes HSP70 at a lower rate than the wild-type parasites.
      Overall, our data suggest that the biological function of the HSP70-II gene is to
      top up HSP70 levels under conditions of stress.

PMID- 16105832
TI  - Processing of m1 RNA at the 3' end protects its primary transcript from
      degradation.
AB  - M1 RNA, the catalytic subunit of Escherichia coli RNase P, is an essential
      ribozyme that processes the 5' leader sequence of precursor tRNAs. It is
      generated by the removal of 36 nucleotides from the 3' end of the primary rnpB
      transcript (pM1 RNA), but the biological significance of this reaction in
      bacterial metabolism remains obscure. In this study, we constructed and analyzed
      bacterial strains carrying mutations in the rne-dependent site of their rnpB
      genes, showing that the 3' processing of M1 RNA is essential for cell viability.
      Furthermore, we demonstrate that pM1 RNA can undergo not only 3' processing but
      also poly(A)-dependent degradation. Therefore, our results suggest that the 3'
      processing of M1 RNA provides a functional mechanism for the protection of its
      primary transcript against degradation.

PMID- 16105833
TI  - The long terminal repeat (LTR) of ERV-9 human endogenous retrovirus binds to NF-Y
      in the assembly of an active LTR enhancer complex NF-Y/MZF1/GATA-2.
AB  - The solitary ERV-9 long terminal repeat (LTR) located upstream of the HS5 site in
      the human beta-globin locus control region exhibits prominent enhancer activity
      in embryonic and erythroid cells. The LTR enhancer contains 14 tandemly repeated
      subunits with recurrent CCAAT, GTGGGGA, and GATA motifs. Here we showed that in
      erythroid K562 cells these DNA motifs bound the following three transcription
      factors: ubiquitous NF-Y and hematopoietic MZF1 and GATA-2. These factors and
      their target DNA motifs exhibited a hierarchy of DNA/protein and protein/protein
      binding affinities: NF-Y/CCAAT > NF-Y/GATA-2 > NF-Y/MZF1 > MZF1/GTGGGGA; GATA
      2/GATA. Through protein/protein interactions, NF-Y bound at the CCAAT motif
      recruited MZF1 and GATA-2, but not Sp1 and GATA-1, and stabilized their binding
      to the neighboring GTGGGGA and GATA sites to assemble a novel LTR enhancer
      complex, NF-Y/MZF1/GATA-2. In the LTR-HS5-epsilonp-GFP plasmid integrated into
      K562 cells, mutation of the CCAAT motif in the LTR enhancer to abolish NF-Y
      binding inactivated the enhancer, closed down the chromatin structure of the
      epsilon-globin promoter, and silenced transcription of the green fluorescent
      protein gene. The results indicated that NF-Y bound at the CCAAT motifs assembled
      a robust LTR enhancer complex, which could act over the intervening DNA to
      remodel the chromatin structure and to stimulate the transcription of the
      downstream gene locus.

PMID- 16105834
TI  - The synthetic cannabinoid R(+)WIN 55,212-2 inhibits the interleukin-1 signaling
      pathway in human astrocytes in a cannabinoid receptor-independent manner.
AB  - R(+)WIN 55,212-2 is a synthetic cannabinoid that controls disease progression in
      models of multiple sclerosis. This is associated with its ability to reduce
      migration of leukocytes into the central nervous system. Because leukocyte
      migration is dependent on induction of adhesion molecules and chemokines by pro
      inflammatory cytokines, we examined the effects of R(+)WIN 55,212-2 on their
      expression. Using 1321N1 astrocytoma and A-172 glioblastoma as cell models we
      show that R(+)WIN 55,212-2, but not its inactive chiral form S(-)WIN 55,212-2,
      strongly inhibits the interleukin-1 (IL-1) induction of the adhesion molecules
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) and the chemokine IL-8. This inhibition is not mediated via the CB1 or
      CB2 cannabinoid receptors, because their selective antagonists and pertussis
      toxin failed to affect the inhibitory effects of R(+)WIN 55,212-2. Furthermore
      reverse transcription-PCR analysis did not detect the expression of either
      receptor in 1321N1 cells. R(+)WIN 55,212-2 was shown to inhibit adhesion molecule
      and chemokine expression at the level of transcription, because it strongly
      inhibited the IL-1 induction of ICAM-1, VCAM-1, and IL-8 mRNAs and blocked the IL
      1 activation of their promoters. The NFkappaB pathway was then assessed as a lead
      target for R(+)WIN 55,212-2. NFkappaB was measured by expression of a transfected
      NFkappaB-regulated reporter gene. Using this assay, R(+)WIN 55,212-2 strongly
      inhibited IL-1 activation of NFkappaB. Furthermore R(+)WIN 55,212-2 inhibited the
      ability of overexpressed Myd88, Tak-1, and IKK-2 to induce the reporter gene
      suggesting that R(+)WIN 55,212-2 acts at or downstream of IKK-2 in the IL-1
      pathway. However R(+)WIN 55,212-2 failed to inhibit IL-1-induced degradation of
      IkappaBalpha, excluding IKK-2 as a direct target. In addition electrophoretic
      mobility shift and chromatin immunoprecipitation assays showed that R(+)WIN
      55,212-2 does not regulate the IL-1-induced nuclear translocation of NFkappaB or
      the ability of the latter to bind to promoters regulating expression of ICAM-1
      and IL-8. These data suggest that R(+)WIN 55,212-2 blocks IL-1 signaling by
      inhibiting the transactivation potential of NFkappaB.

PMID- 16105835
TI  - NAP1 modulates binding of linker histone H1 to chromatin and induces an extended
      chromatin fiber conformation.
AB  - NAP1 (nucleosome assembly protein 1) is a histone chaperone that has been
      described to bind predominantly to the histone H2A.H2B dimer in the cell during
      shuttling of histones into the nucleus, nucleosome assembly/remodeling, and
      transcription. Here it was examined how NAP1 interacts with chromatin fibers
      isolated from HeLa cells. NAP1 induced a reversible change toward an extended
      fiber conformation as demonstrated by sedimentation velocity ultracentrifugation
      experiments. This transition was due to the removal of the linker histone H1. The
      H2A.H2B dimer remained stably bound to the native fiber fragments and to fibers
      devoid of linker histone H1. This was in contrast to mononucleosome substrates,
      which displayed a NAP1-induced removal of a single H2A.H2B dimer from the core
      particle. The effect of NAP1 on the chromatin fiber structure was examined by
      scanning/atomic force microscopy. A quantitative image analysis of approximately
      36,000 nucleosomes revealed an increase of the average internucleosomal distance
      from 22.3 +/- 0.4 to 27.6 +/- 0.6 nm, whereas the overall fiber structure was
      preserved. This change reflects the disintegration of the chromatosome due to
      binding of H1 to NAP1 as chromatin fibers stripped from H1 showed an average
      nucleosome distance of 27.4 +/- 0.8 nm. The findings suggest a possible role of
      NAP1 in chromatin remodeling processes involved in transcription and replication
      by modulating the local linker histone content.

PMID- 16105836
TI  - Fully metallated S134N Cu,Zn-superoxide dismutase displays abnormal mobility and
      intermolecular contacts in solution.
AB  - S134N copper-zinc superoxide dismutase (SOD1) is one of the many mutant SOD1
      proteins known to cause familial amyotrophic lateral sclerosis. Earlier studies
      demonstrated that partially metal-deficient S134N SOD1 crystallized in filament
      like arrays with abnormal contacts between the individual protein molecules.
      Because protein aggregation is implicated in SOD1-linked familial amyotrophic
      lateral sclerosis, abnormal intermolecular interactions between mutant SOD1
      proteins could be relevant to the mechanism of pathogenesis in the disease. We
      have therefore applied NMR methods to ascertain whether abnormal contacts also
      form between S134N SOD1 molecules in solution and whether Cys-6 or Cys-111 plays
      any role in the aggregation. Our studies demonstrate that the behavior of fully
      metallated S134N SOD1 is dramatically different from that of fully metallated
      wild type SOD1 with a region of subnanosecond mobility located close to the site
      of the mutation. Such a high degree of mobility is usually seen only in the apo
      form of wild type SOD1, because binding of zinc to the zinc site normally
      immobilizes that region. In addition, concentration-dependent chemical shift
      differences were observed for S134N SOD1 that were not observed for wild type
      SOD1, indicative of abnormal intermolecular contacts in solution. We have here
      also established that the two free cysteines (6 and 111) do not play a role in
      this behavior.

PMID- 16105837
TI  - Multiple conformations in the ligand-binding site of the yeast nuclear pore
      targeting domain of Nup116p.
AB  - The yeast nucleoporin Nup116p plays an important role in mRNA export and protein
      transport. We have determined the solution structure of the C-terminal 147
      residues of this protein, the region responsible for targeting the protein to the
      nuclear pore complex (NPC). The structure of Nup116p-C consists of a large beta
      sheet sandwiched against a smaller one, flanked on both sides by alpha-helical
      stretches, similar to the structure of its human homolog, NUP98. In unliganded
      form, Nup116p-C exhibits evidence of exchange among multiple conformations,
      raising the intriguing possibility that it may adopt distinct conformations when
      bound to different partners in the NPC. We have additionally shown that a peptide
      from the N terminus of the nucleoporin Nup145p-C binds Nup116p-C. This previously
      unknown interaction may explain the unusual asymmetric localization pattern of
      Nup116p in the NPC. Strikingly, the exchange phenomenon observed in the unbound
      state is greatly reduced in the corresponding spectra of peptide-bound Nup116p-C,
      suggesting that the binding interaction stabilizes the domain conformation. This
      study offers a high resolution view of a yeast nucleoporin structural domain and
      may provide insights into NPC architecture and function.

PMID- 16105838
TI  - TLR3 and TLR7 are targeted to the same intracellular compartments by distinct
      regulatory elements.
AB  - Toll-like receptor (TLR) 3 and TLR7 are indispensable for host defense against
      viral infection by recognizing virus-derived RNAs and are localized to
      intracellular membranes via an unknown mechanism. We recently reported
      experiments with chimeric Toll-like receptors that suggested that the subcellular
      distribution of TLRs may be defined by their transmembrane and/or cytoplasmic
      domains. Here we demonstrate that the intracellular localization of TLR3 is
      achieved by a 23-amino acid sequence (Glu(727) to Asp(749)) present in the linker
      region between the transmembrane domain and Toll-interleukin 1 receptor
      resistance (TIR) domain. In contrast, the intracellular localization of TLR7 is
      achieved by its transmembrane domain. These elements also targeted a heterologous
      type I transmembrane protein CD25 to the intracellular compartment that contained
      TLR3 and TLR7. Despite their using distinct regulatory elements for intracellular
      localization, TLR3 was found to co-localize with TLR7. In addition, TLR3 and TLR7
      were preferentially localized near phagosomes containing apoptotic cell
      particles. These findings reveal that TLR3 and TLR7 contain unique targeting
      sequences, which differentially lead them to the same intracellular compartments
      and adjacent to phagosomes containing apoptotic cell particles, where these
      receptors may access their ligands for the induction of immune responses against
      viral infection.

PMID- 16105839
TI  - Mutational analysis of the catalytic domain of O-linked N-acetylglucosaminyl
      transferase.
AB  - O-Linked N-acetylglucosaminyltransferase (OGT) catalyzes the transfer of O-linked
      GlcNAc to serine/threonine residues of a variety of target proteins, many of
      which have been implicated in such diseases as diabetes and neurodegeneration.
      The addition of O-GlcNAc to proteins occurs in response to fluctuations in
      cellular concentrations of UDP-GlcNAc, which result from nutrients entering the
      hexosamine biosynthetic pathway. However, the molecular mechanisms involved in
      sugar nucleotide recognition and transfer to protein are poorly understood. We
      employed site-directed mutagenesis to target potentially important amino acid
      residues within the two conserved catalytic domains of OGT (CD I and CD II),
      followed by an in vitro glycosylation assay to evaluate N
      acetylglucosaminyltransferase activity after bacterial expression. Although many
      of the amino acid substitutions caused inactivation of the enzyme, we identified
      three amino acid residues (two in CD I and one in CD II) that produced viable
      enzymes when mutated. Structure-based homology modeling revealed that these
      permissive mutants may be either in or near the sugar nucleotide-binding site.
      Our findings suggest a model in which the two conserved regions of the catalytic
      domain, CD I and CD II, contribute to the formation of a UDP-GlcNAc-binding
      pocket that catalyzes the transfer of O-GlcNAc to substrate proteins.
      Identification of viable OGT mutants may facilitate examination of its role in
      nutrient sensing and signal transduction cascades.

PMID- 16105840
TI  - Phosphorylation of RelA/p65 on serine 536 defines an I{kappa}B{alpha}-independent
      NF-{kappa}B pathway.
AB  - The association of the NF-kappaB p65/p50 dimer with IkappaBalpha plays a pivotal
      role in regulating its nuclear translocation and gene transcription. In addition,
      serine phosphorylation at various sites of the p65 subunit has been shown to be
      important in initiating transcription. Here we demonstrate that the regulation of
      nuclear translocation of p65 phosphorylated at serine 536 is not dependent on
      IkappaBalpha. Stimulation of either Jurkat or normal human T cells resulted in
      the nuclear translocation of phospho-p65 (Ser(536)). In addition, the phospho-p65
      (Ser(536)) was not associated with either IkappaBalpha or p50, and the nuclear
      translocation of phospho-p65 (Ser(536)), but not total p65, was unaffected by the
      proteosome inhibitor MG-132, which blocks IkappaB protein degradation and
      prevents p65/p50 dimer nuclear translocation. Accordingly, the co-expression of a
      dominant negative mutant of IkappaBalpha blocked the transcriptional activity
      mediated by wild type but not the dominant positive p65 mutant (S536D).
      Furthermore, the transfection of the S536D form of p65 led to the induction of
      interleukin-8 transcription following stimulation, whereas the S536A form, which
      cannot be phosphorylated at this site, did not. Together, the findings suggest
      that p65 phosphorylated on serine 536 is not associated with or regulated by
      IkappaBalpha, that it has a distinct set of target genes, and that it may
      represent a noncanonical NF-kappaB pathway that is independent of IkappaBalpha
      regulation.

PMID- 16105841
TI  - Lethal cutaneous disease in transgenic mice conditionally expressing type I human
      T cell leukemia virus Tax.
AB  - Type I human T cell leukemia virus (HTLV-I) is etiologically linked with adult T
      cell leukemia, an aggressive and usually fatal expansion of activated CD4+ T
      lymphocytes that frequently traffic to skin. T cell transformation induced by
      HTLV-I involves the action of the 40-kDa viral Tax transactivator protein. Tax
      both stimulates the HTLV-I long terminal repeat and deregulates the expression of
      select cellular genes by altering the activity of specific host transcription
      factors, including cyclic AMP-responsive element-binding protein
      (CREB)/activating transcription factor, NF-kappaB/Rel, and serum response factor.
      To study initiating events involved in HTLV-I Tax-induced T cell transformation,
      we generated "Tet-off" transgenic mice conditionally expressing in a lymphocyte
      restricted manner (EmuSR alpha promoter-enhancer) either wild-type Tax or mutant
      forms of Tax that selectively compromise the NF-kappaB (M22) or CREB/activating
      transcription factor (M47) activation pathways. Wild-type Tax and M47 Tax
      expressing mice, but not M22-Tax expressing mice, developed progressive alopecia,
      hyperkeratosis, and skin lesions containing profuse activated CD4 T cell
      infiltrates with evidence of deregulated inflammatory cytokine production. In
      addition, these animals displayed systemic lymphadenopathy and splenomegaly.
      These findings suggest that Tax-mediated activation of NF-kappaB plays a key role
      in the development of this aggressive skin disease that shares several features
      in common with the skin disease occurring during the preleukemic stage in HTLV-I
      infected patients. Of note, this skin disease completely resolved when Tax
      transgene expression was suppressed by administration of doxycycline, emphasizing
      the key role played by this viral oncoprotein in the observed pathology.

PMID- 16105842
TI  - Galectin-1 interacts with the {alpha}5{beta}1 fibronectin receptor to restrict
      carcinoma cell growth via induction of p21 and p27.
AB  - Surface binding of galectin family members has the potential to link distinct
      glycan structures to growth regulation. Therefore, we addressed the
      antiproliferative potential of galectin-1 (Gal-1) in a panel of carcinoma cell
      lines. We discovered growth inhibition by Gal-1 in epithelial tumor cell lines
      from different origins and provide evidence that this effect requires functional
      interaction with the alpha5beta1 integrin. Antiproliferative effects result from
      inhibition of the Ras-MEK-ERK pathway and consecutive transcriptional induction
      of p27. We have further identified two Sp1-binding sites in the p27 promoter as
      crucial for Gal-1 responsiveness. Inhibition of the Ras-MEK-ERK cascade by Gal-1
      increased Sp1 transactivation and DNA binding due to reduced threonine
      phosphorylation of Sp1. Furthermore, Gal-1 induced p21 transcription and
      selectively increased p27 protein stability. Gal-1-mediated accumulation of p27
      and p21 inhibited cyclin-dependent kinase 2 activity and ultimately resulted in
      G(1) cell cycle arrest and growth inhibition. These data define a novel mechanism
      whereby Gal-1 regulates epithelial tumor cell homeostasis via carbohydrate
      dependent interaction with the alpha5beta1 integrin.

PMID- 16105843
TI  - Self-association of IQGAP1: characterization and functional sequelae.
AB  - The scaffolding protein IQGAP1 participates in numerous cellular functions by
      binding to target proteins such as actin, calmodulin, E-cadherin, beta-catenin,
      Cdc42, Rac1, and CLIP-170. IQGAP1 regulates the cytoskeleton, promotes cell
      motility, and modulates E-cadherin-mediated cell-cell adhesion. However, how
      IQGAP1 exerts its functions in vivo is still unclear. In this study we
      investigate the self-association of IQGAP1 and its role in IQGAP1 function.
      Endogenous IQGAP1 co-immunoprecipitated from MCF-7 cells with IQGAP1 tagged with
      enhanced green fluorescent protein, indicating that IQGAP1 self-associates in
      cells. In vitro assays confirmed that IQGAP1 can self-associate and that this
      effect is mediated by the N-terminal half of the protein. Gel filtration analysis
      suggested that full-length IQGAP1 exists as a combination of monomers, dimers,
      and larger oligomers. Analysis performed with multiple fragments of IQGAP1
      narrowed the self-association region to amino acids 763-863. In support of this
      observation, a peptide comprising residues 763-863 disrupted self-association of
      full-length IQGAP1 in a dose-dependent manner. Similarly, deleting this sequence
      from IQGAP1 abolished binding to full-length IQGAP1. In addition, the ability of
      IQGAP1 to increase the amount of active Cdc42 in cells is abrogated upon removal
      of this region. Consistent with these findings, transfection into cells of a
      peptide containing the self-association domain significantly reduced the amount
      of active Cdc42 in cell lysates. These observations define a sequence of IQGAP1
      that is necessary for its oligomerization and demonstrate that self-association
      is required for the normal cellular function of IQGAP1.

PMID- 16105844
TI  - Phosphorylation of Numb family proteins. Possible involvement of Ca2+/calmodulin
      dependent protein kinases.
AB  - To search for the substrates of Ca2+/calmodulin-dependent protein kinase I (CaM
      KI), we performed affinity chromatography purification using either the
      unphosphorylated or phosphorylated (at Thr177) GST-fused CaM-KI catalytic domain
      (residues 1-293, K49E) as the affinity ligand. Proteomic analysis was then
      carried out to identify the interacting proteins. In addition to the detection of
      two known CaM-KI substrates (CREB and synapsin I), we identified two Numb family
      proteins (Numb and Numbl) from rat tissues. These proteins were unphosphorylated
      and were bound only to the Thr177-phosphorylated CaM-KI catalytic domain. This
      finding is consistent with the results demonstrating that Numb and Numbl were
      efficiently and stoichiometrically phosphorylated in vitro at equivalent Ser
      residues (Ser264 in Numb and Ser304 in Numbl) by activated CaM-KI and also by two
      other CaM-Ks (CaM-KII and CaM-KIV). Using anti-phospho-Numb/Numbl antibody, we
      observed the phosphorylation of Numb family proteins in various rat tissue
      extracts, and we also detected the ionomycin-induced phosphorylation of
      endogenous Numb at Ser264 in COS-7 cells. The present results revealed that the
      Numb family proteins are phosphorylated in vivo as well as in vitro. Furthermore,
      we found that the recruitment of 14-3-3 proteins was the functional consequence
      of the phosphorylation of the Numb family proteins. Interaction of 14-3-3 protein
      with phosphorylated Numbl-blocked dephosphorylation of Ser304. Taken together,
      these results indicate that the Numb family proteins may be intracellular targets
      for CaM-Ks, and they may also be regulated by phosphorylation-dependent
      interaction with 14-3-3 protein.

PMID- 16105845
TI  - Provocation of sudden heart rate oscillation with adenosine exposes abnormal QT
      responses in patients with long QT syndrome: a bedside test for diagnosing long
      QT syndrome.
AB  - AIMS: As arrhythmias in the long QT syndrome (LQTS) are triggered by heart rate
      deceleration or acceleration, we speculated that the sudden bradycardia and
      subsequent tachycardia that follow adenosine injection would unravel QT changes
      of diagnostic value in patients with LQTS. METHODS AND RESULTS: Patients (18 LQTS
      and 20 controls) received intravenous adenosine during sinus rhythm. Adenosine
      was injected at incremental doses until atrioventricular block or sinus pauses
      lasting 3 s occurred. The QT duration and morphology were studied at baseline and
      at the time of maximal bradycardia and subsequent tachycardia. Despite similar
      degree of adenosine-induced bradycardia (longest R-R 1.7+/-0.7 vs. 2.2+/-1.3 s
      for LQTS and controls, P=NS), the QT interval of LQT patients increased by 15.8+/
      13.1%, whereas the QT of controls increased by only 1.5+/-6.7% (P<0.001).
      Similarly, despite similar reflex tachycardia (shortest R-R 0.58+/-0.07 vs.
      0.55+/-0.07 s for LQT patients and controls, P=NS), LQTS patients developed
      greater QT prolongation (QTc=569+/-53 vs. 458+/-58 ms for LQT patients and
      controls, P<0.001). The best discriminator was the QTc during maximal
      bradycardia. Notched T-waves were observed in 72% of LQT patients but in only 5%
      of controls during adenosine-induced bradycardia (P<0.001). CONCLUSION: By
      provoking transient bradycardia followed by sinus tachycardia, this adenosine
      challenge test triggers QT changes that appear to be useful in distinguishing
      patients with LQTS from healthy controls.

PMID- 16105846
TI  - Addition of an angiotensin receptor blocker to full-dose ACE-inhibition:
      controversial or common sense?
AB  - Both angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor
      blockers (ARBs) interfere with the activity of the renin-angiotensin system (RAS)
      in a different way. Theoretically, one might expect beneficial effects when they
      are used in combination, as a more complete suppression of the RAS can be
      achieved. But can this additional effect still be seen in patients on full-dose
      ACE-inhibition? Several controlled trials demonstrated that combination therapy
      can have additional benefits in hypertensive patients, in chronic heart failure
      patients, and in both diabetic and non-diabetic nephropathy patients. However,
      the clinical benefit was not always as pronounced as expected and not every
      patient will benefit from dual blockade of the RAS. There is some evidence of a
      less pronounced effect of combination therapy when a full dose of the ACE
      inhibitor is given. However, it is well known that ACE-inhibitors cannot
      completely suppress the formation of angiotensin II, in particular, when the RAS
      is activated. Indeed, clinical trials indicated that add-on therapy with an ARB
      was especially of use when the RAS remained activated despite full-dose ACE
      inhibitor treatment. In summary, combination of a full-dose ACE-inhibitor and an
      ARB can be a rational choice in selected patients.

PMID- 16105847
TI  - Six minute walk test.

PMID- 16105848
TI  - End-systolic pressure/volume relationship during dobutamine stress echo: a
      prognostically useful non-invasive index of left ventricular contractility.
AB  - AIMS: Left ventricular end-systolic pressure-volume relationship (PVR) provides a
      robust, relatively load-insensitive evaluation of contractility and can be
      assessed non-invasively during exercise echo. Dobutamine might provide an
      exercise-independent alternative approach to assess inotropic reserve. The
      feasibility of a non-invasive estimation of PVR during dobutamine stress in the
      echo lab and its relationship with subsequent clinical events was assessed.
      METHODS AND RESULTS: We enrolled 137 consecutive patients referred for dobutamine
      stress echo. To build the PVR, the force was determined at different heart rate
      increments during stepwise dobutamine infusion as the ratio of the systolic
      pressure/end-systolic volume index. The PVR at increasing heart rate was flat
      biphasic in 65 and up-sloping in 72 patients: 42 patients underwent surgery and
      95 patients were treated medically (median follow-up, 18 months; interquartile
      range, 12-24). Events occurred in 18 patients (death in eight, acute heart
      failure in 10); a flat-biphasic PVR was independent predictor of events
      (RR=10.16, P<0.01). CONCLUSION: PVR is feasible during dobutamine stress. This
      index of global contractility is reasonably simple, does not affect the imaging
      time, and only minimally prolongs the off-line analysis time. It allows unmasking
      quite different, and heterogeneous, contractility reserve patterns underlying a
      given ejection fraction at rest. The best survival is observed in patients with
      up-sloping PVR, whereas flat-biphasic pattern is a strong predictor of cardiac
      events.

PMID- 16105849
TI  - Serum hepatocyte growth factor levels predict long-term clinical outcome after
      percutaneous coronary revascularization.
AB  - AIMS: To evaluate, in patients referred for elective percutaneous coronary
      revascularization (PCR) without heparin pre-treatment, the relationship between
      baseline serum levels of the angiogenic growth factors, vascular endothelial
      growth factor (VEGF) and hepatocyte growth factor (HGF), and clinical outcome.
      METHODS AND RESULTS: In 488 consecutive patients undergoing elective coronary
      angioplasty, hsC-reactive protein, HGF, and VEGF levels were measured before
      heparin administration. The primary endpoint, a composite of death and myocardial
      infarction, occurred in 44 patients at a median follow-up of 14.9 months. At
      baseline, VEGF levels were related to C-reactive protein levels and inversely
      related to age; HGF levels were related to C-reactive protein levels, diabetes,
      and recent clinical instability. In the univariate analysis, HGF had a
      significant positive relationship (P=0.003) with the primary endpoint. A similar
      trend was observed for VEGF (P=0.11). The only three variables significantly
      associated with the primary endpoint in the multivariable Cox model were HGF
      (P=0.004), C-reactive protein (P=0.007), and diabetes (P=0.04). CONCLUSION: Our
      results demonstrate that in patients, without heparin pre-treatment, referred for
      PCR, a high serum level of HGF is an independent predictor of clinical events
      during follow-up and is correlated with other surrogate measures of the activity
      of atherosclerosis.

PMID- 16105850
TI  - How many patients with heart failure are eligible for cardiac resynchronization?
      Insights from two prospective cohorts.
AB  - AIMS: To determine what proportion of patients with heart failure are eligible
      for cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Eligibility
      criteria from the trials establishing the efficacy of CRT were applied to two
      prospective cohorts: the first enrolled patients with newly diagnosed heart
      failure discharged from 103 hospitals between April 1999 and March 2001 ('the
      hospital discharge cohort'); the second enrolled patients seen in a specialized
      clinic between August 2003 and January 2004 ('the specialty clinic cohort'). In
      the hospital discharge cohort, 73 patients (3% of the 2640 patients with
      ischaemic or dilated cardiomyopathy and 1% of all 9096 patients with heart
      failure discharged alive) met trial eligibility criteria: LVEF< or =0.35, QRS >
      or =120 ms, sinus rhythm, and NYHA class III or IV symptoms despite the treatment
      with ACE-inhibitor/angiotensin receptor blocker and beta-blocker. In the
      specialty clinic cohort, 54 patients (21% of the 263 patients with ischaemic or
      dilated cardiomyopathy and 17% of all 309 patients with heart failure) met these
      criteria. If persistent symptoms despite taking spironolactone were required for
      CRT eligibility, then the proportions qualifying dropped to 1% in the hospital
      discharge cohort and 18% in the specialty clinic cohort. CONCLUSION: Few heart
      failure patients meet trial eligibility criteria for CRT.

PMID- 16105851
TI  - Oxidative stress in obstructive sleep apnoea.
AB  - AIMS: Any sustained elevation of oxidative stress in patients with obstructive
      sleep apnoea (OSA) might help explain their increased risk for cardiovascular
      diseases. We tested the hypothesis that measures of oxidative stress are
      increased in otherwise healthy subjects with OSA when compared to closely matched
      OSA-free control subjects. METHODS AND RESULTS: Plasma indices of oxidative
      stress and lipid peroxidation [thiobarbituric acid-reactive substances (TBARS),
      oxidized LDL (oxLDL), isoprostanes] were measured in 41 moderate-severe OSA males
      without other diseases and in 35 matched controls first before sleep, then after
      4 h of untreated OSA, and again in the morning after 4 h of effective treatment
      with continuous positive airway pressure (CPAP). Plasma levels of oxLDL, TBARS,
      and isoprostanes in OSA patients (n=34, 26, 17, respectively) were comparable to
      the controls (n=28, 27, 15 for the three markers, respectively). Neither
      untreated OSA nor CPAP treatment nor normal sleep affected levels of any of the
      three measures of oxidative stress. There was no association between the severity
      of sleep apnoea and any measure of oxidative stress. CONCLUSION: Otherwise
      healthy OSA patients, without any other co-morbidities, do not manifest evidence
      for higher oxidative stress and lipid peroxidation. Thus, oxidative stress and
      lipid peroxidation do not appear to be key mediators of increased cardiovascular
      disease in OSA patients.

PMID- 16105852
TI  - Discrepancy between viable counts and light output as viability measurements,
      following ciprofloxacin challenge of self-bioluminescent Pseudomonas aeruginosa
      biofilms.
AB  - OBJECTIVES: To utilize bioluminescence to follow the effect of ciprofloxacin
      challenge on Pseudomonas aeruginosa biofilms. METHODS: The Sorbarod continuous
      perfusion culture system was used for the cultivation of biofilms of a self
      bioluminescent strain of P. aeruginosa PAO1. Biofilms were challenged with
      ciprofloxacin (5 mg/L) in the perfusing medium for 3 h and allowed to recover to
      pre-challenge population levels before initiation of a second 3 h challenge. In
      addition to determining eluate and biofilm cell survival by conventional viable
      plate counts, light output was monitored via a luminometer and a low-light-level
      ICCD camera, to give an indication of metabolism. The effect of drug challenge on
      biofilm structure was investigated using an environmental scanning electron
      microscope, which allowed discernment of changes to the three-dimensional biofilm
      architecture. RESULTS: On challenge with ciprofloxacin, eluate light output
      measurements declined to a lesser extent than viable counts for the same samples
      and also indicated that post-challenge recovery of the biofilm metabolism did not
      occur as rapidly as suggested by viable count data. Photon detection by ICCD
      camera allowed real-time, non-invasive imaging of metabolic activity within
      intact biofilms. CONCLUSIONS: The application of a bioluminescent reporter strain
      to biofilm research provides valuable real-time positional data on the efficacy
      of anti-biofilm treatment strategies.

PMID- 16105853
TI  - Three years of state fiscal struggles: how did Medicaid and SCHIP fare?
AB  - During 2003-05, states faced some of the largest budget shortfalls since World
      War II. With a focus on Medicaid and SCHIP, we examine budget decisions in eight
      states during this period. Increasing Medicaid enrollment because of the economic
      down-turn and rising health care costs compounded state budget shortfalls as
      state revenues dropped; problems peaked in 2004. States, however, were reluctant
      to confront their budget deficits as long-term problems and implemented a variety
      of one-time revenue strategies and spending reductions that push fiscal problems
      into the future. The arrival of federal fiscal relief in late 2003 helped states
      avoid deeper cuts but did not eliminate cutbacks.

PMID- 16105854
TI  - Overexpression in transgenic tobacco reveals different roles for the rice
      homeodomain gene OsBIHD1 in biotic and abiotic stress responses.
AB  - The rice OsBIHD1 gene encodes a transcriptional factor belonging to the
      homeodomain class. It had previously been shown to be activated by treatment with
      benzothiadiazole, a chemical inducer of disease resistance, and in an
      incompatible interaction between rice and the blast fungus. To allow a better
      understanding of the function of OsBIHD1 in plant disease resistance response,
      the OsBIHD1 gene in tobacco was overexpressed by Agrobacterium-mediated leaf disc
      transformation with a construct containing the OsBIHD1 ORF under control of the
      35S promoter. Overexpression of the rice OsBIHD1 gene in some of the transgenic
      tobacco lines led to some morphological abnormalities in the top buds and roots.
      The transgenic tobacco plants showed an elevated level of defence-related PR-1
      gene expression and enhanced disease resistance against infection by tomato
      mosaic virus, tobacco mosaic virus, and Phytophthora parasitica var. nicotianae.
      However, the transgenic tobacco plants overexpressing OsBIHD1 showed enhanced
      sensitivity to salt and oxidative stress as compared with the wild-type plants.
      The results suggested that the OsBIHD1 protein may be positively involved in
      activating expression of the defence-related genes in disease resistance
      responses, and is also important in rice development and abiotic stress
      tolerance.

PMID- 16105855
TI  - Functional role of red (retro)-carotenoids as passive light filters in the leaves
      of Buxus sempervirens L.: increased protection of photosynthetic tissues?
AB  - Red (retro)-carotenoids accumulate in chloroplasts of Buxus sempervirens leaves
      during the process of winter leaf acclimation. As a result of their irregular
      presence, different leaf colour phenotypes can be found simultaneously in the
      same location. Five different colour phenotypes (green, brown, red, orange, and
      yellow), with a distinct pattern of pigment distribution and concentration, have
      been characterized. Leaf reddening due to the presence of anthocyanins or
      carotenoids, is a process frequently observed in plant species under
      photoinhibitory situations. Two main hypotheses have been proposed to explain the
      function of such colour change: antioxidative protection exerted by red-coloured
      molecules, and green light filtering. The potential photoprotective role of red
      (retro-) carotenoids as light filters was tested in Buxus sempervirens leaves. In
      shade leaves of this species the upper (adaxial) mesophyll of the lamina was
      replaced by the equivalent upper part of a different colour phenotype. These
      hybrid leaves were exposed to a photoinhibitory treatment in order to compare the
      photoprotective effect exerted by adaxial parts of phenotypes with a different
      proportion of red (retro)-carotenoids in the lower mesophyll of a shade leaf. The
      results indicated that the presence of red (retro)-carotenoids in the upper
      mesophyll did not increase photoprotection of the lower mesophyll when compared
      with chlorophyll, and the best protection was achieved by an upper green layer.
      This was due to the fact that the extent of photoinhibition was proportional to
      the amount of red light transmitted by the upper mesophyll and/or to the
      chlorophyll pool located above. These results do not exclude a protective
      function of carotenoids in the upper leaf layer, but imply that, at least under
      the conditions of this experiment, the accumulation of red pigments in the outer
      leaf layers does not increase photoprotection in the lower mesophyll.

PMID- 16105856
TI  - Enhanced secretion of tropane alkaloids in Nicotiana tabacum hairy roots
      expressing heterologous hyoscyamine-6beta-hydroxylase.
AB  - Hyoscyamine-6beta-hydroxylase (H6H; EC 1.14.11.11) catalyses oxidative reactions
      in the biosynthetic pathway leading from hyoscyamine to the more pharmaceutically
      valuable tropane alkaloid scopolamine. The h6h gene encoding H6H from Hyoscyamus
      niger was introduced, under the control of the CaMV 35S promoter, into non
      hyoscyamine-producing Nicotiana tabacum and hyoscyamine-producing Hyoscyamus
      muticus. The transformation was performed using a binary vector system based on
      Agrobacterium rhizogenes. Production of scopolamine in hairy roots was clearly
      correlated with the 35S-h6h transcript expression. The engineered N. tabacum and
      H. muticus hairy roots were studied for the production of scopolamine and other
      tropane and nicotine alkaloids after feeding the cultures with exogenous
      hyoscyamine. N. tabacum hairy roots carrying the 35S-h6h transgene showed a more
      efficient uptake of hyoscyamine from the culture medium and a higher rate of
      bioconversion of hyoscyamine to scopolamine than those of H. muticus. In
      particular, the secretion of scopolamine in N. tabacum hairy roots was remarkably
      high, up to 85% of the total scopolamine being released to the culture medium.
      Exogenous hyoscyamine also caused changes in nicotine alkaloid accumulation in N.
      tabacum hairy roots.

PMID- 16105857
TI  - Regulation of muscle GLUT4 enhancer factor and myocyte enhancer factor 2 by AMP
      activated protein kinase.
AB  - As the primary glucose transporter in skeletal muscle, GLUT4 is an important
      factor in the regulation of blood glucose. We previously reported that
      stimulation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4
      carboxamide-1-beta-d-ribofuranoside (AICAR) increased GLUT4 expression in muscle.
      GLUT4 enhancer factor (GEF) and myocyte enhancer factor 2 (MEF2) have been shown
      to be important for normal GLUT4 expression because deletion or truncation of the
      consensus sequences on the promoter causes depressed GLUT4 mRNA expression. This
      led to the current study to investigate possible roles for GEF and MEF2 in
      mediating the activation of GLUT4 gene transcription in response to AMPK. Here we
      show that, although AMPK does not appear to phosphorylate MEF2A, AMPK directly
      phosphorylates the GEF protein in vitro. MEF2 and GEF are activated in response
      to AMPK as we observed translocation of both to the nucleus after AICAR
      treatment. Nuclear MEF2 protein content was increased after 2 h, and GEF protein
      was increased in the nucleus 1 and 2 h post-AICAR treatment. Last, GEF and MEF2
      increase in binding to the GLUT4 promoter within 2 h after AICAR treatment. Thus
      we conclude that GEF and MEF2 mediate the AMPK-induced increase in transcription
      of skeletal muscle GLUT4. AMPK can phosphorylate GEF and in response to AICAR,
      GEF, and MEF2 translocate to the nucleus and have increased binding to the GLUT4
      promoter.

PMID- 16105858
TI  - Coordinated alteration of hepatic gene expression in fatty acid and triglyceride
      synthesis in LCAT-null mice is associated with altered PUFA metabolism.
AB  - Complete lecithin:cholesterol acyltransferase (LCAT) deficiency is associated
      with fasting hypertriglyceridemia (HTG). We recently reported that, in ldlr(-/
      )xlcat(-/-) mice, fasting HTG is associated with hepatic triglyceride
      overproduction in association with an upregulation of the hepatic srebp1 gene and
      altered expression of its target genes in lipogenesis and gluconeogenesis. We
      further investigated the role of hepatic polyunsaturated fatty acid (PUFA)
      metabolism in the modulation of the lipid phenotypes. In the ldlr(-/-)xlcat(-/-)
      mice, using the ldlr(-/-)xlcat(+/+) littermate as controls, the hepatic level of
      cholesterol esters (CE) were reduced by 61.0% whereas the 20:4-CE and 22:6-CE
      contents were each reduced by >80%. In contrast, the hepatic levels of 20:4- and
      22:6-containing phospholipid (PL) species were either unchanged or mildly
      elevated. Similar alterations of the hepatic PUFA in CE and in PL were also
      observed in the lcat(-/-) mice compared with their wild-type controls. In ldlr(-/
      )xlcat(-/-) mice, hepatic mRNA level was markedly reduced for Delta-6 desaturase
      (fads2) (70.2%) and acyl-CoA:cholesterol acyltransferase-2 (soat2) (57.0%). A
      similar pattern of gene expression change was also observed in the lcat(-/-)
      single-knockout mice. In contrast, the acyl-CoA:diacylglycerol acyltransferase-2
      (dgat2) mRNA level was 1.7-fold upregulated in the double-knockout mice. In
      summary, we observed coordinated alterations in hepatic expression of the gene
      for fads2, soat2, and dgat2, resulting in a reduction in total hepatic PUFA pool
      and differentially in the PUFA-CE pool, in association with an increase in dgat2
      gene expression for promoting triglyceride synthesis and secretion. Some of the
      phenotypes are not readily explained by known mechanisms and may represent novel
      regulatory pathways.

PMID- 16105859
TI  - Mechanisms for abnormal postprandial glucose metabolism in type 2 diabetes.
AB  - To assess mechanisms for postprandial hyperglycemia, we used a triple-isotope
      technique ([?3-(3)H]glucose and [(14)C]bicarbonate and oral [6,6
      dideutero]glucose iv) and indirect calorimetry to compare components of glucose
      release and pathways for glucose disposal in 26 subjects with type 2 diabetes and
      15 age-, weight-, and sex-matched normal volunteers after a standard meal. The
      results were as follows: 1) diabetic subjects had greater postprandial glucose
      release (P<0.001) because of both increased endogenous and meal-glucose release;
      2) the greater endogenous glucose release (P<0.001) was due to increased
      gluconeogenesis (P<0.001) and glycogenolysis (P=0.01); 3) overall tissue glucose
      uptake, glycolysis, and storage were comparable in both groups (P>0.3); 4)
      glucose clearance (P<0.001) and oxidation (P=0.004) were reduced, whereas
      nonoxidative glycolysis was increased (P=0.04); and 5) net splanchnic glucose
      storage was reduced by approximately 45% (P=0.008) because of increased glycogen
      cycling (P=0.03). Thus in type 2 diabetes, postprandial hyperglycemia is
      primarily due to increased glucose release; hyperglycemia overcomes the effects
      of impaired insulin secretion and sensitivity on glucose transport, but
      intracellular defects persist so that pathways of glucose metabolism are abnormal
      and glucose is shunted away from normal sites of storage (e.g., liver and muscle)
      into other tissues.

PMID- 16105860
TI  - Steroidogenesis in human aldosterone-secreting adenomas and adrenal hyperplasias:
      effects of hypoxia in vitro.
AB  - The synthesis of adrenal steroids requires molecular oxygen. Because arterial
      hypoxemia is a common clinical condition, the purpose of the present study was to
      examine steroidogenesis in vitro under physiological changes in O(2) tension
      (Po(2)) in cells from human adrenal glands with aldosterone-secreting adenomas
      (ASA; n=3) or with bilateral adrenal hyperplasia causing Cushing's syndrome
      (n=4). A decrease in Po(2) from 150 mmHg (mild hyperoxia) to 80 mmHg had minimal
      effect on steroid production. A reduction to 40 mmHg (still well within the
      physiological range) significantly inhibited cAMP- and ACTH-stimulated
      aldosterone, cortisol, and dehydroepiandrosterone (DHEA) production from ASA.
      Furthermore, cortisol and DHEA production in cells from histologically normal
      tissue, adjacent to ASA and from bilateral adrenal hyperplasias, was also
      inhibited under a Po(2) of 40 mmHg. We conclude that physiological decreases in
      Po(2) to levels typical for adrenal venous Po(2) under mild hypoxia inhibit
      steroidogenesis. These studies may have implications for oxygen therapy in
      critically ill patients with functional adrenal insufficiency, as well as for
      therapeutic options in patients with adrenal neoplasms.

PMID- 16105861
TI  - Decreased insulin-dependent glucose transport by chronic ethanol feeding is
      associated with dysregulation of the Cbl/TC10 pathway in rat adipocytes.
AB  - Heavy alcohol consumption is an independent risk factor for type 2 diabetes.
      Although the exact mechanism by which alcohol contributes to the increased risk
      is unknown, impaired glucose disposal is a likely target. Insulin-stimulated
      glucose disposal in adipocytes is regulated by two separate and independent
      pathways, the PI3K pathway and the Cbl/TC10 pathway. Previous studies suggest
      that chronic ethanol feeding impairs insulin-stimulated glucose transport in
      adipocytes in a PI3K-independent manner. In search of potential targets of
      ethanol that would affect insulin-stimulated glucose transport, we investigated
      the effects of 4-wk ethanol feeding to male Wistar rats on the Cbl/TC10 pathway
      in isolated adipocytes. Chronic ethanol feeding inhibited insulin-stimulated cCbl
      phosphorylation compared with pair feeding. Insulin receptor and Akt/PKB
      phosphorylation were not affected by ethanol feeding. Chronic ethanol exposure
      also impaired cCbl and TC10 recruitment to a lipid raft fraction isolated from
      adipocytes by detergent extraction. Furthermore, chronic ethanol feeding
      increased the amount of activated TC10 and filamentous actin in adipocytes at
      baseline and abrogated the ability of insulin to further activate TC10 or
      polymerize actin. These results demonstrate that the impairment in insulin
      stimulated glucose transport observed in adipocytes after chronic ethanol feeding
      to rats is associated with a disruption of insulin-mediated Cbl/TC10 signaling
      and actin polymerization.

PMID- 16105862
TI  - L-Arginine infusion increases glucose clearance during prolonged exercise in
      humans.
AB  - Nitric oxide synthase (NOS) inhibition has been shown in humans to attenuate
      exercise-induced increases in muscle glucose uptake. We examined the effect of
      infusing the NO precursor L-arginine (L-Arg) on glucose kinetics during exercise
      in humans. Nine endurance-trained males cycled for 120 min at 72+/-1% Vo(2 peak)
      followed immediately by a 15-min "all-out" cycling performance bout. A [6,6
      (2)H]glucose tracer was infused throughout exercise, and either saline alone
      (Control, CON) or saline containing L-Arg HCL (L-Arg, 30 g at 0.5 g/min) was
      confused in a double-blind, randomized order during the last 60 min of exercise.
      L-Arg augmented the increases in glucose rate of appearance, glucose rate of
      disappearance, and glucose clearance rate (L-Arg: 16.1+/-1.8 ml.min(-1).kg(-1);
      CON: 11.9+/- 0.7 ml.min(-1).kg(-1) at 120 min, P<0.05) during exercise, with a
      net effect of reducing plasma glucose concentration during exercise. L-Arg
      infusion had no significant effect on plasma insulin concentration but attenuated
      the increase in nonesterified fatty acid and glycerol concentrations during
      exercise. L-Arg infusion had no effect on cycling exercise performance. In
      conclusion, L-Arg infusion during exercise significantly increases skeletal
      muscle glucose clearance in humans. Because plasma insulin concentration was
      unaffected by L-Arg infusion, greater NO production may have been responsible for
      this effect.

PMID- 16105863
TI  - Role of the hepatic sympathetic nerves in the regulation of net hepatic glucose
      uptake and the mediation of the portal glucose signal.
AB  - Portal glucose delivery enhances net hepatic glucose uptake (NHGU) relative to
      peripheral glucose delivery. We hypothesize that the sympathetic nervous system
      normally restrains NHGU, and portal glucose delivery relieves the inhibition. Two
      groups of 42-h-fasted conscious dogs were studied using arteriovenous difference
      techniques. Denervated dogs (DEN; n=10) underwent selective sympathetic
      denervation by cutting the nerves at the celiac nerve bundle near the common
      hepatic artery; control dogs (CON; n=10) underwent a sham procedure. After a 140
      min basal period, somatostatin was given along with basal intraportal infusions
      of insulin and glucagon. Glucose was infused peripherally to double the hepatic
      glucose load (HGL) for 90 min (P1). In P2, glucose was infused intraportally (3-4
      mg.kg(-1).min(-1)), and the peripheral glucose infusion was reduced to maintain
      the HGL for 90 min. This was followed by 90 min (P3) in which portal glucose
      infusion was terminated and peripheral glucose infusion was increased to maintain
      the HGL. P1 and P3 were averaged as the peripheral glucose infusion period (PE).
      The average HGLs (mg.kg(-1).min(-1)) in CON and DEN were 55+/-3 and 54+/-4 in the
      peripheral periods and 55+/-3 and 55+/-4 in P2, respectively. The arterial
      insulin and glucagon levels remained basal in both groups. NHGU (mg.kg(-1).min(
      1)) in CON averaged 1.7+/-0.3 during PE and increased to 2.9+/-0.3 during P2.
      NHGU (mg.kg(-1).min(-1)) was greater in DEN than CON (P<0.05) during PE (2.9+/
      0.4) and failed to increase significantly (3.2+/-0.2) during P2 (not significant
      vs. CON). Selective sympathetic denervation increased NHGU during hyperglycemia
      but significantly blunted the response to portal glucose delivery.

PMID- 16105864
TI  - Acute and chronic effects of glucose and carbachol on insulin secretion and
      phospholipase C activation: studies with diazoxide and atropine.
AB  - The acute and chronic effects of 20 mM glucose and 10 microM carbachol on beta
      cell responses were investigated. Acute exposure of rat islets to 20 mM glucose
      increased glucose usage rates and resulted in a large insulin-secretory response
      during a dynamic perifusion. The secretory, but not the metabolic, effect of 20
      mM glucose was abolished by simultaneous exposure to 100 microM diazoxide.
      Glucose (20 mM) significantly increased inositol phosphate (IP) accumulation, an
      index of phospholipase C (PLC) activation, from [(3)H]inositol-prelabeled islets.
      Diazoxide, but not atropine, abolished this effect as well. Unlike 20 mM glucose,
      10 microM carbachol (in the presence of 5 mM glucose) increased IP accumulation
      but had no effect on insulin secretion or glucose (5 mM) metabolism. The IP
      effect was abolished by 50 microM atropine but not by diazoxide. Chronic 3-h
      exposure of islets to 20 mM glucose or 10 microM carbachol profoundly reduced
      both the insulin-secretory and PLC responses to a subsequent 20 mM glucose
      stimulus. The adverse effects of chronic glucose exposure were abolished by
      diazoxide but not by atropine. In contrast, the adverse effects of carbachol were
      abolished by atropine but not by diazoxide. Prior 3 h of exposure to 20 mM
      glucose or carbachol had no inhibitory effect on glucose metabolism. Significant
      secretory responses could be evoked from 20 mM glucose- or carbachol-pretreated
      islets by the inclusion of forskolin. These findings support the concept that an
      early event in the evolution of beta-cell desensitization is the impaired
      activation of islet PLC.

PMID- 16105865
TI  - Evaluation of tests for microalbuminuria screening in patients with diabetes.
AB  - BACKGROUND: The first step in the diagnosis of diabetic nephropathy is to measure
      albumin in a spot urine sample. The aim of this study was to assess the accuracy
      of urinary albumin concentration (UAC), urinary albumin-to-creatinine ratio
      (UACR), and the Micral-Test II in a random urine specimen (RUS) for
      microalbuminuria screening in diabetes mellitus. METHODS: Two hundred and seventy
      eight patients collected 24 h timed urine specimens followed by RUS. Albumin
      (immunoturbidimetry) and creatinine were measured in protein-negative (Combur
      Test) urine samples. Samples were classified as normoalbuminuric [24 h urinary
      albumin excretion rate (UAER) <20 microg/min; n = 189] and microalbuminuric (UAER
      =20-199 microg/min; n = 89). Micral-Test II readings were performed in 130 RUS.
      Receiver operating characteristics (ROC) curves were constructed using UAER as
      the reference standard. RESULTS: The areas under the ROC curves were similar for
      UAC (0.934+/-0.032) and UACR (0.920+/-0.035; P = 0.626), but the Micral-Test II
      had lower accuracy to diagnose microalbuminuria (area = 0.846+/-0.047) than UAC
      (P = 0.014). The first cutoff point with 100% sensitivity for UAC was 14.4 mg/l
      (specificity =77.2%), and 15.7 mg/g for UACR (specificity =73.0%). Concerning the
      Micral-Test II, sensitivity and specificity for the 20 mg/l cutoff point were
      90.0 and 46.0%, respectively. The agreement between UAER and the Micral-Test II
      for microalbuminuria diagnosis was 55.8% (kappa = 0.22; P < 0.001). The cost of
      diagnosing microalbuminuria was 1.74 dollars(UAC), 2.00 dollars (UACR) and 4.09
      dollars (Micral-Test II) per patient. CONCLUSIONS: Measurement of UAC in a RUS
      was the best choice for the diagnosis screening of microalbuminuria in diabetic
      patients, considering cost and accuracy.

PMID- 16105866
TI  - Dialysis encephalopathy secondary to aluminum toxicity, diagnosed by bone biopsy.

PMID- 16105867
TI  - Measurement of relative blood volume changes during haemodialysis: merits and
      limitations.

PMID- 16105868
TI  - Beneficial haemodynamic and renal sodium handling effects of combined midodrine
      and octreotide treatment in a cirrhotic patient with large hepatic hydrothorax
      and mild ascites.

PMID- 16105869
TI  - The effects of highly active antiretroviral therapy on albuminuria in HIV
      infected persons: results from a randomized trial.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected patients receiving highly
      active antiretroviral therapy (HAART) regimens, especially those containing
      protease inhibitors (PIs), are at increased risk for cardiovascular events.
      Albuminuria is a known independent predictor for the development of
      cardiovascular disease and may potentially increase in patients receiving PIs.
      Alternatively, albuminuria may improve with HAART as a result of treating renal
      parenchymal HIV infection. Longitudinal studies have not been performed
      previously addressing the effects of HAART on albuminuria. METHODS: We evaluated
      the effects of HAART on albumin to creatinine ratios (ACRs) during the initial 64
      weeks of therapy in 68 previously untreated HIV-infected subjects, without pre
      existing diagnosed diabetes or hypertension, enrolled in a randomized trial
      comparing PI-based (n = 32) with non-PI-based (n = 36) HAART regimens. We also
      estimated the prevalence of albuminuria, defined as an ACR > or =3.4 mg/mmol, in
      these subjects prior to initiation of HAART. RESULTS: The changes in ACR over the
      initial 64 weeks of therapy in those receiving PIs [0.0 mg/mmol (-0.4, 0.3)] and
      in those not receiving PIs [0.0 mg/mmol (-0.5, 0.3)] were not significantly
      different. There was also no significant difference in the change in the ACR in
      the group as a whole. However, albuminuria at baseline was found in seven (10%)
      subjects. Five of these seven subjects had substantial improvements in ACR,
      ranging from 45 to 95%, with HAART use; three subjects had resolution of
      albuminuria. ACR at baseline significantly correlated with the baseline HIV-1 RNA
      level (r = 0.25; P = 0.04) and negatively with CD4 cell count (r = -0.25; P =
      0.04). CONCLUSION: Albuminuria in HIV-infected, treatment-naive patients was
      found more frequently than expected and may be influenced by baseline immune
      status. Although we did not observe an effect of HAART on ACR during the first 64
      weeks of therapy, we cannot exclude the possibility that HAART may be beneficial
      in those patients with significant albuminuria prior to treatment. Research in
      larger cohorts is required to investigate more definitively the associations
      between immune status, antiretroviral therapies and renal function in HIV
      infected patients.

PMID- 16105870
TI  - Using an anomalous brachial artery as an alternative choice of arteriovenous
      shunt feeding artery.

PMID- 16105871
TI  - Steroid sparing strategies in renal transplantation.

PMID- 16105872
TI  - Outcomes and costs of abciximab versus eptifibatide for percutaneous coronary
      intervention.
AB  - BACKGROUND: Patients undergoing percutaneous coronary intervention (PCI) with
      stent placement are often prescribed glycoprotein IIb/IIIa inhibitors. However,
      drug selection is often based on clinicians' preference and cost because few
      studies have directly compared abciximab and eptifibatide. OBJECTIVE: To compare
      clinical outcomes and total hospital costs of abciximab and eptifibatide in
      patients undergoing stent placement during PCI in a real-world setting. METHODS:
      A retrospective cohort analysis was conducted of 960 patients administered
      abciximab or eptifibatide for intracoronary stent placement between 1999 and 2001
      at a tertiary care hospital. The primary outcome was bleeding, defined as major,
      moderate, or minor according to published criteria. Secondary outcomes included
      in-hospital death, myocardial infarction, revascularization, and the triple
      composite endpoint of those outcomes, thrombocytopenia, length-of-stay, and total
      hospital costs. Pearson's chi(2) analysis, Fisher's exact test, and ANOVA were
      used for statistical analysis. RESULTS: The frequency of bleeding complications
      based on severity was similar between abciximab and eptifibatide: major (2.4% vs
      2.8%), moderate (12.4% vs 10.5%), and minor (4.0% vs 3.9%), respectively (p =
      0.86). Secondary clinical outcomes were also similar between groups (p > 0.05).
      Total costs for hospitalization were significantly greater for abciximab compared
      with eptifibatide ($16,383 +/- 6799 vs $14,115 +/- 6285; p < 0.001). Drug
      acquisition costs were also significantly greater for abciximab compared with
      eptifibatide ($508 +/- 159 vs $465 +/- 263; p = 0.003). CONCLUSIONS: In patients
      undergoing stent placement during PCI, abciximab and eptifibatide are comparable
      in terms of safety and effectiveness despite significant differences in
      hospitalization and acquisition costs.

PMID- 16105873
TI  - Levofloxacin-induced acute fulminant hepatic failure in a patient with chronic
      hepatitis B infection.
AB  - OBJECTIVE: To report a case of possible levofloxacin-induced acute fulminant
      hepatic failure. CASE SUMMARY: An unconscious 55-year-old woman was hospitalized
      with the diagnosis of hepatic encephalopathy. The patient had received
      levofloxacin 500 mg daily for 10 days because of an upper respiratory infection.
      Her past medical history revealed hepatitis B surface antigen positivity as an
      asymptomatic hepatitis B virus carrier for 10 years. After hospitalization,
      treatment included plasmapheresis and supportive care. The patient's
      consciousness improved on the second day of treatment. Other etiologies of
      fulminant hepatic failure were ruled out, suggesting levofloxacin-induced
      fulminant hepatic failure. Although the patient received supportive treatment,
      her condition gradually deteriorated and she died 12 weeks after admission to our
      hospital. An objective causality assessment revealed that the adverse event was
      possibly related to levofloxacin. DISCUSSION: Levofloxacin is widely used because
      of its broad spectrum of antimicrobial activity. As of August 9, 2005, to our
      knowledge, only one case of fulminant hepatic failure in relation to levofloxacin
      has previously been published. We believe that, in our patient, the relationship
      between levofloxacin and her illness is clear because of the negative results in
      the etiological studies, the short time between the drug's administration and the
      development of disease, and the pathologic findings suggestive of drug-induced
      hepatitis. CONCLUSIONS: Clinicians should be aware of the possibility of severe
      hepatic injury associated with levofloxacin when prescribing this drug.

PMID- 16105874
TI  - A novel dileucine lysosomal-sorting-signal mediates intracellular EGF-receptor
      retention independently of protein ubiquitylation.
AB  - One of the main goals of this study was to understand the relationship between an
      epidermal growth factor (EGF) receptor dileucine (LL)-motif (679-LL) required for
      lysosomal sorting and the protein ubiquitin ligase CBL. We show that receptors
      containing 679-AA (di-alanine) substitutions that are defective for ligand
      induced degradation nevertheless bind CBL and undergo reversible protein
      ubiquitylation similar to wild-type receptors. We also demonstrate that 679-LL
      but not CBL is required for EGF receptor downregulation by an endosomal membrane
      protein encoded by human adenoviruses that uncouples internalization from post
      endocytic sorting to lysosomes. 679-LL is necessary for endosomal retention as
      well as degradation by the adenovirus protein, and is also transferable to
      reporter molecules. Using NMR spectroscopy, we show that peptides with wild-type
      679-LL or mutant 679-AA sequences both exhibit alpha-helical structural
      propensities but that this structure is not stable in water. A similar analysis
      carried out in hydrophobic media showed that the alpha-helical structure of the
      wild-type peptide is stabilized by specific interactions mediated by side-chains
      in both leucine residues. This structure distinguishes 679-LL from other
      dileucine-based sorting-signals with obligatory amino-terminal acidic residues
      that are recognized in the form of an extended beta or beta-like conformation.
      Taken together, these data show that 679-LL is an alpha-helical stabilizing motif
      that regulates a predominant step during lysosomal sorting, involving
      intracellular retention under both sub-saturating and saturating conditions.

PMID- 16105875
TI  - Evidence for the presence of a low-mass beta1 integrin on the cell surface.
AB  - Although the cell line K562 reportedly expresses a single species of beta1
      integrin, alpha5beta1, surface staining with monoclonal antibodies JB1A, 12G10
      and B3B11 to the beta1 chain clearly demonstrated differences in the expression
      levels of the epitopes detected by these antibodies. The present studies were
      initiated to determine the basis for this molecular heterogeneity in the
      integrins. Cross-linking of surface integrins with B3B11 caused their selective
      aggregation. This distribution was similar to that observed for the alpha5 chain.
      In contrast, cross-linking the beta1 chains with 12G10 did not cause
      codistribution of alpha5, suggesting that these two species were not associated
      on the cell surface. Immunoprecipitates of the surface integrins of K562 cells
      indicated the presence of 120 and 140 kDa forms of the beta1 chain which were
      detected by 12G10 and B3B11, respectively. Immunological, biochemical and mass
      spectrometric analysis of K562 surface integrins also failed to demonstrate the
      presence of any alpha chain in association with the 120 kDa species of beta1 of
      K562 cells. Treatment of the two forms of beta1 with PGNase reduced their masses
      to approximately 90 kDa, suggesting that N-glycosylation was responsible for the
      mass differences. Collectively, these results provide evidence for a novel
      species of beta1 on the cell surface, which does not appear to be associated with
      any alpha chain. The data also suggest that differences in glycosylation may be
      involved in defining the association between the integrin alpha and beta chains
      and the functional properties of these integrins.

PMID- 16105876
TI  - alpha(v)beta3-integrin-dependent activation of focal adhesion kinase mediates NF
      kappaB activation and motogenic activity by HIV-1 Tat in endothelial cells.
AB  - Once in the extracellular environment, the transactivator protein HIV-1 Tat
      exerts several pleiotropic effects by interacting with different cellular
      receptors, including integrin alpha(v)beta3. Real-time surface plasmon resonance
      analysis reveals that Tat/alpha(V)beta3 interaction occurs with rapid kinetics
      (association and dissociation rates equal to 1.16 x 10(7) M(-1) s(-1) and 3.78 x
      10(-1) s(-1), respectively) and high affinity (dissociation constant = 32 nM).
      Through this interaction, substratum-immobilized Tat promotes adhesion and
      motogenic activity in endothelial cells. Also, alpha(v)beta(3)/Tat interaction
      triggers the activation of focal adhesion kinase, RhoA and pp60src.
      Overexpression of the dominant negative form of focal adhesion kinase, but not of
      an inactive Leu1034Ser substitution mutant isoform, impairs the activation of
      focal adhesion kinase and RhoA, but not that of pp60src, without affecting
      endothelial cell adhesion and spreading. alpha(v)beta3/Tat interaction triggers
      the activation of NF-kappaB in endothelial cells in a focal adhesion kinase-,
      RhoA- and pp60src-dependent manner, as shown in dominant negative focal adhesion
      kinase transfectants or using specific pharmacological inhibitors. Finally, the
      activation of focal adhesion kinase, RhoA, NF-kappaB and pp60src are required to
      mediate the motogenic activity of Tat in endothelial cells. Since Tat accumulates
      in an immobilized form in the extracellular matrix, these results provide new
      biochemical and biological insights about alpha(v)beta3/Tat interaction
      exploitable for the design of anti-Tat strategies.

PMID- 16105877
TI  - Contribution of sequence variation in Drosophila actins to their incorporation
      into actin-based structures in vivo.
AB  - Actin is a highly conserved protein important for many cellular functions
      including motility, contraction in muscles and intracellular transport. Many
      eukaryotic genomes encode multiple actin protein isoforms that differ from each
      other by only a few residues. We addressed whether the sequence differences
      between actin paralogues in one species affect their ability to integrate into
      the large variety of structures generated by filamentous actin. We thus
      ectopically expressed all six Drosophila actins as fusion proteins with green
      fluorescent protein (GFP) in a variety of embryonic, larval and adult fly
      tissues. We found that each actin was able to integrate into most actin
      structures analysed. For example, in contrast to studies in mammalian cells, the
      two Drosophila cytoplasmic actins were incorporated into muscle sarcomeres.
      However, there were differences in the efficiency with which each actin was
      incorporated into specific actin structures. The most striking difference was
      observed within the Z-lines of the sarcomeres: one actin was specifically
      excluded and we mapped this feature to one or both of two residues within the C
      terminal half of the protein. Thus, in Drosophila, the primary sequence of
      different actins does affect their ability to incorporate into actin structures,
      and so specific GFPactins may be used to label certain actin structures
      particularly well.

PMID- 16105878
TI  - Quantitative analysis of changes in spatial distribution and plus-end geometry of
      microtubules involved in plant-cell cytokinesis.
AB  - The cell plate of higher plants is formed within a ribosome-excluding cell plate
      assembly matrix. Phragmoplast microtubules facilitate cell-plate formation by
      forming a scaffold that directs Golgi-derived vesicles to the forming cell plate.
      Here, we analyse the effects of the cell-plate assembly matrix on phragmoplast
      microtubule plus-end geometry by electron tomography of cryogenically fixed
      Arabidopsis meristem cells. Five distinct microtubules plus-end geometries are
      seen--blunt, extended, horned, flared and hybrid extended/horned. We have
      quantified and mapped these types of plus-end morphology during the different
      stages of cell-plate formation and analysed the effects of cell-plate assembly
      matrix association on microtubule plus-end morphologies. Our results show that
      somatic-type phragmoplast microtubules do not interdigitate at the cell plate mid
      line. The cell-plate assembly matrix is shown to stabilize microtubule plus ends,
      as evidenced by the fact that of these microtubules that do not terminate in such
      a matrix, 40-80% are horn-shaped (shrinking), whereas of those that end in such a
      matrix, 50-70% are blunt (metastable). Also, a third of the blunt-ended
      microtubules within the cell-plate assembly matrix end at a distance of
      approximately 30 nm from the cell plate.

PMID- 16105879
TI  - Distinctive nuclear organisation of centromeres and regions involved in
      pluripotency in human embryonic stem cells.
AB  - Nuclear organisation is thought to be important in regulating gene expression.
      Here we investigate whether human embryonic stem cells (hES) have a particular
      nuclear organisation, which could be important for maintaining their pluripotent
      state. We found that whereas the nuclei of hES cells have a general gene-density
      related radial organisation of chromosomes, as is seen in differentiated cells,
      there are also distinctive localisations for chromosome regions and gene loci
      with a role in pluripotency. Chromosome 12p, a region of the human genome that
      contains clustered pluripotency genes including NANOG, has a more central nuclear
      localisation in ES cells than in differentiated cells. On chromosome 6p we find
      no overall change in nuclear chromosome position, but instead we detect a
      relocalisation of the OCT4 locus, to a position outside its chromosome territory.
      There is also a smaller proportion of centromeres located close to the nuclear
      periphery in hES cells compared to differentiated cells. We conclude that hES
      cell nuclei have a distinct nuclear architecture, especially at loci involved in
      maintaining pluripotency. Understanding this level of hES cell biology provides a
      framework within which other large-scale chromatin changes that may accompany
      differentiation can be considered.

PMID- 16105880
TI  - MAP kinase pathways.

PMID- 16105881
TI  - Non-Smad TGF-beta signals.
AB  - During the past 10 years, it has been firmly established that Smad pathways are
      central mediators of signals from the receptors for transforming growth factor
      beta (TGF-beta) superfamily members to the nucleus. However, growing biochemical
      and developmental evidence supports the notion that alternative, non-Smad
      pathways also participate in TGF-beta signalling. Non-Smad signalling proteins
      have three general mechanisms by which they contribute to physiological responses
      to TGF-beta: (1) non-Smad signalling pathways directly modify (e.g.
      phosphorylate) the Smads and thus modulate the activity of the central effectors;
      (2) Smads directly interact and modulate the activity of other signalling
      proteins (e.g. kinases), thus transmitting signals to other pathways; and (3) the
      TGF-beta receptors directly interact with or phosphorylate non-Smad proteins,
      thus initiating parallel signalling that cooperates with the Smad pathway in
      eliciting physiological responses. Thus, non-Smad signal transducers under the
      control of TGF-beta provide quantitative regulation of the signalling pathway,
      and serve as nodes for crosstalk with other major signalling pathways, such as
      tyrosine kinase, G-protein-coupled or cytokine receptors.

PMID- 16105882
TI  - On mammary stem cells.
AB  - Mammary gland stem cells are a quiescent and self-renewing population within the
      mammary gland that are capable of giving rise to the differentiated ductal,
      alveolar and myoepithelial cells. To identify mammary gland stem cells, several
      investigators have employed a variety of methods including: non-adherent
      mammosphere cultures; 5-bromo-2-deoxy-uridine (BrdU) label-retention studies;
      cell-surface markers, such as Sca1 and CD49f; and Hoechst dye efflux. These
      methods have helped identify and further characterize signal transduction
      pathways such as the Notch, Wnt and Hedgehog pathways that may be important for
      the self-renewal and fate determination of mammary gland stem cells. Stem cells
      within the mammary gland have been proposed to underpin many types of breast
      cancer. A better understanding of the signal transduction pathways and the
      molecules that are responsible for the self-renewal and survival of these cells
      will be essential in the design of more effective therapies aimed at the
      eradication of both cancer-initiating cells and breast cancer stem cells.

PMID- 16105883
TI  - Role of the spindle-pole-body protein ApsB and the cortex protein ApsA in
      microtubule organization and nuclear migration in Aspergillus nidulans.
AB  - Nuclear migration and positioning in Aspergillus nidulans depend on microtubules,
      the microtubule-dependent motor protein dynein, and auxiliary proteins, two of
      which are ApsA and ApsB. In apsA and apsB mutants nuclei are clustered and show
      various kinds of nuclear navigation defects, although nuclear migration itself is
      still possible. We studied the role of several components involved in nuclear
      migration through in vivo fluorescence microscopy using fluorescent-protein
      tagging. Because ApsA localizes to the cell cortex and mitotic spindles were
      immobile in apsA mutants, we suggest that astral microtubule-cortex interactions
      are necessary for oscillation and movement of mitotic spindles along hyphae, but
      not for post-mitotic nuclear migration. Mutation of apsA resulted in longer and
      curved microtubules and displayed synthetic lethality in combination with the
      conventional kinesin mutation DeltakinA. By contrast, ApsB localized to spindle
      pole bodies (the fungal centrosome), to septa and to spots moving rapidly along
      microtubules. The number of cytoplasmic microtubules was reduced in apsB mutants
      in comparison to the wild type, indicating that cytoplasmic microtubule
      nucleation was affected, whereas mitotic spindle formation appeared normal.
      Mutation of apsB suppressed dynein null mutants, whereas apsA mutation had no
      effect. We suggest that nuclear positioning defects in the apsA and apsB mutants
      are due to different effects on microtbule organisation. A model of spindle-pole
      body led nuclear migration and the roles of dynein and microtubules are
      discussed.

PMID- 16105884
TI  - VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of
      endogenous PDGF-B-PDGFRbeta signaling.
AB  - Combined stimulation with VEGF-A, FGF-2, or PDGF-BB has emerged as a potent
      strategy for therapeutic angiogenesis, although the mechanisms underlying the
      synergism of these factors are not well understood. In the present study, we
      investigated the mechanism of synergism between VEGF-A and FGF-2 by using
      Matrigel plug assay in vivo and embryonic stem cell (ESC)-derived VEGF receptor 2
      (VEGFR2)-positive cells in vitro. Experiments in vitro revealed that, in addition
      to having direct mitogenic effects, these molecules enhance intercellular PDGF-B
      signaling in a cell-type specific manner: VEGF-A enhances endothelial PDGF-B
      expression, whereas FGF-2 enhances mural PDGF receptor beta (PDGFRbeta)
      expression. Co-stimulation with VEGF-A and FGF-2 caused significant mural cell
      recruitment in vitro and formation of functional neovasculature in vivo, compared
      with single-agent stimulation. These effects were abrogated not only by anti
      PDGFRbeta neutralizing antibody, but also by exogenous PDGF-BB, which could
      overwhelm the endogenous PDGF-BB distribution. These findings indicated the
      importance of preservation of the periendothelial PDGF-BB gradient. Thus, we
      demonstrated that the directional enhancement of endogenous PDGF-B-PDGFRbeta
      signaling is indispensable for the synergistic effect of VEGF-A and FGF-2 on
      neoangiogenesis in adults. The findings provide insights into the mechanisms
      underlying the effects of co-stimulation by growth factors, which could lead to
      rational design of therapeutic angiogenic strategies.

PMID- 16105885
TI  - Ubiquitously expressed secretory carrier membrane proteins (SCAMPs) 1-4 mark
      different pathways and exhibit limited constitutive trafficking to and from the
      cell surface.
AB  - Secretory carrier membrane proteins (SCAMPs) 1-4 are ubiquitously expressed and
      are major components of the eukaryotic cell surface recycling system. We
      investigated whether different SCAMPs function along distinct pathways and
      whether they behave like itinerant cargoes or less mobile trafficking machinery.
      In NRK cells, we show by immunofluorescence microscopy that different SCAMPs are
      concentrated mostly adjacent to one another in the trans-Golgi network and
      endosomal recycling compartment. By immunoelectron microscopy, they were shown to
      be close neighbors on individual transferrin-containing endosomal elements and on
      the plasma membrane. Within the internal endosomal network, SCAMPs are located
      distal to rab5-containing endosomes, and the individual isoforms appear to mark
      pathways that diverge from the constitutive recycling route and that may be
      distinguished by different adaptors, especially AP-1 and AP-3. Based on
      comparisons of SCAMP localization with endocytosed transferrin as well as live
      imaging of GFP-SCAMP1, we show that SCAMPs are concentrated within the motile
      population of early and recycling endosomes; however, they are not detected in
      newly formed transferrin-containing endocytic vesicles or in vesicles recycling
      transferrin to the surface. Also, they are not detected in constitutive secretory
      carriers marked by VSV-G. Their minimal recycling to the surface is reflected by
      their inability to relocate to the plasma membrane upon inhibition of
      endocytosis. Thus SCAMPs exhibit limited exchange between the cell surface and
      internal recycling systems, but within each of these sites, they form a mosaic
      with individual isoforms marking distinct pathways and potentially functioning as
      trafficking machinery at sites of vesicle formation and fusion. A corollary of
      these findings is that early endosomes exist as a distinct SCAMP-containing
      compartment and are not formed de novo by fusion of endocytic vesicles.

PMID- 16105886
TI  - Distinct mechanisms govern the localisation of Drosophila CLIP-190 to unattached
      kinetochores and microtubule plus-ends.
AB  - CLIP-170 was the first microtubule plus-end-tracking protein to be described, and
      is implicated in the regulation of microtubule plus-ends and their interaction
      with other cellular structures. Here, we have studied the cell-cycle-dependent
      mechanisms which localise the sole Drosophila melanogaster homologue CLIP-190.
      During mitosis, CLIP-190 localises to unattached kinetochores independently of
      spindle-checkpoint activation. This localisation depends on the dynein-dynactin
      complex and Lis1 which also localise to unattached kinetochores. Further analysis
      revealed a hierarchical dependency between the proteins with respect to their
      kinetochore localisation. An inhibitor study also suggested that the motor
      activity of dynein is required for the removal of CLIP-190 from attached
      kinetochores. In addition, we found that CLIP-190 association to microtubule plus
      ends is regulated during the cell cycle. Microtubule plus-end association is
      strong in interphase and greatly attenuated during mitosis. Another microtubule
      plus-end tracking protein, EB1, directly interacts with the CAP-Gly domain of
      CLIP-190 and is required to localise CLIP-190 at microtubule plus-ends. These
      results indicate distinct molecular requirements for CLIP-190 localisation to
      unattached kinetochores in mitosis and microtubule ends in interphase.

PMID- 16105887
TI  - Relation between viral fitness and immune escape within the hepatitis C virus
      protease.
AB  - BACKGROUND: The hepatitis C virus (HCV) mutates within human leucocyte antigen
      (HLA) class I restricted immunodominant epitopes of the non-structural (NS) 3/4A
      protease to escape cytotoxic T lymphocyte (CTL) recognition and promote viral
      persistence. However, variability is not unlimited, and sometimes almost absent,
      and factors that restrict viral variability have not been defined experimentally.
      AIMS: We wished to explore whether the variability of the immunodominant CTL
      epitope at residues 1073-1081 of the NS3 protease was limited by viral fitness.
      PATIENTS: Venous blood was obtained from six patients (four HLA-A2+) with chronic
      HCV infection and from one HLA-A2+ patient with acute HCV infection. METHODS:
      NS3/4A genes were amplified from serum, cloned in a eukaryotic expression
      plasmid, sequenced, and expressed. CTL recognition of naturally occurring and
      artificially introduced escape mutations in HLA-A2-restricted NS3 epitopes were
      determined using CTLs from human blood and genetically immunised HLA-A2
      transgenic mice. HCV replicons were used to test the effect of escape mutations
      on HCV protease activity and RNA replication. RESULTS: Sequence analysis of
      NS3/4A confirmed low genetic variability. The major viral species had functional
      proteases with 1073-1081 epitopes that were generally recognised by cross
      reactive human and murine HLA-A2 restricted CTLs. Introduction of mutations at
      five positions of the 1073-1081 epitope prevented CTL recognition but three of
      these reduced protease activity and RNA replication. CONCLUSIONS: Viral fitness
      can indeed limit the variability of HCV within immunological epitopes. This helps
      to explain why certain immunological escape variants never appear as a major
      viral species in infected humans.

PMID- 16105888
TI  - Serum from achalasia patients alters neurochemical coding in the myenteric plexus
      and nitric oxide mediated motor response in normal human fundus.
AB  - BACKGROUND AND AIMS: Achalasia is a disease of unknown aetiology. An immune
      mechanism has been suggested on the basis of previous morphological observations.
      The objective of this study was to test whether the serum of achalasia patients
      could reproduce the phenotype and functional changes that occur with disease
      progression in an ex vivo human model. METHODS: Specimens of normal human fundus
      were maintained in culture in the presence of serum from patients with achalasia,
      gastro-oesophageal reflux disease (GORD), or healthy subjects (controls).
      Immunohistochemical detection of choline acetyltransferase (ChAT), neurone
      specific enolase (NSE), vasoactive intestinal polypeptide (VIP), nitric oxide
      synthase (NOS), and substance P was carried out in whole mounts of gastric fundus
      myenteric plexus. In addition, the effects of achalasia serum on electrical field
      stimulation (EFS) induced contractions were measured in circular muscle
      preparations. RESULTS: Serum from achalasia patients did not affect the number of
      myenteric neurones. Tissues incubated with serum from achalasia patients showed a
      decrease in the proportion of NOS (-26% of NSE positive neurones; p=0.016) and
      VIP (-54%; p=0.09) neurones, and a concomitant increase in ChAT neurones (+16%;
      p<0.001) compared with controls. In contrast, GORD serum did not modify the
      phenotype of myenteric neurones. Area under the curve of EFS induced relaxations
      (abolished by N-nitro-L-arginine methyl ester) was significantly decreased
      following incubation with serum from achalasia patients compared with controls (
      7.6 (2.6) v -14.5 (5.0); p=0.036). CONCLUSIONS: Serum from achalasia patients can
      induce phenotypic and functional changes which reproduce the characteristics of
      the disease. Further identification of putative seric factors and mechanisms
      involved could lead to the development of novel diagnostic and/or therapeutic
      strategies in achalasia.

PMID- 16105889
TI  - Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1
      cytokine production, cytotoxicity, and survival in coeliac disease.
AB  - BACKGROUND AND AIMS: Epithelium derived interleukin (IL)-15 signalling via IL
      15Ralpha is critical for the development, activation, and survival of
      intraepithelial lymphocytes (IEL). We aimed to better understand the IL-15 driven
      effects on IEL underlying mucosal damage and lymphomagenesis in coeliac disease
      (CD). METHODS: Enterocytes, IEL, and lamina propria mononuclear cells (LPMC) were
      isolated from 46 patients with uncomplicated CD (25 untreated and 21 treated) and
      22 controls. IL-15 and IL-15Ralpha expression were determined by immunoblotting.
      Secretion of IL-15, interferon gamma (IFN-gamma), tumour necrosis factor alpha
      (TNF-alpha), and granzyme B into cell culture supernatants was assessed by ELISA.
      The ability of IL-15 to regulate IEL proliferation, perforin/granzyme dependent
      cytotoxicity, and apoptosis was tested by adding different combinations of IL-15,
      IL-15 blocking antibody, or chloroquine to IEL cultured alone or with Caco-2
      cells as target. IL-15 mucosal levels were also determined by ELISA in five
      patients with complicated CD (two ulcerative jejunoileites, one refractory sprue,
      and two enteropathy associated T cell lymphomas) tested for T cell receptor gamma
      chain clonality. RESULTS: IL-15 was overexpressed in untreated CD enterocytes and
      LPMC, and in the mucosa of complicated CD patients and uncomplicated untreated CD
      patients, where its levels correlated with the degree of mucosal damage.
      Enterocytes from untreated, but not treated, CD patients and controls secreted IL
      15. Untreated CD IEL, characterised by higher IL-15Ralpha expression, showed
      increased proliferation, production of IFN-gamma and TNF-alpha, and
      perforin/granzyme dependent cytotoxicity, and a decreased propensity to apoptosis
      in response to IL-15. CONCLUSIONS: Our findings suggest that IL-15 plays a
      crucial role in the generation of epithelial damage in active CD. Its promotion
      of IEL survival in CD may predispose to the emergence of T cell clonal
      proliferations. Blocking IL-15, by suppressing uncontrolled IEL activation and
      survival, has the potential to provide new therapeutic tools to prevent tissue
      damage and lymphomagenesis in CD.

PMID- 16105890
TI  - Specific probiotic therapy attenuates antibiotic induced visceral
      hypersensitivity in mice.
AB  - BACKGROUND AND AIMS: Abdominal pain and discomfort are common symptoms in
      functional disorders and are attributed to visceral hypersensitivity. These
      symptoms fluctuate over time but the basis for this is unknown. Here we examine
      the impact of changes in gut flora and gut inflammatory cell activity on visceral
      sensitivity. METHODS: Visceral sensitivity to colorectal distension (CRD) was
      assessed at intervals in healthy mice for up to 12 weeks, and in mice before and
      after administration of dexamethasone or non-absorbable antibiotics with or
      without supplementation with Lactobacillus paracasei (NCC2461). Tissue was
      obtained for measurement of myeloperoxidase activity (MPO), histology, microbiota
      analysis, and substance P (SP) immunolabelling. RESULTS: Visceral
      hypersensitivity developed over time in healthy mice maintained without sterile
      precautions. This was accompanied by a small increase in MPO activity.
      Dexamethasone treatment normalised MPO and CRD responses. Antibiotic treatment
      perturbed gut flora, increased MPO and SP immunoreactivity in the colon, and
      produced visceral hypersensitivity. Administration of Lactobacillus paracasei in
      spent culture medium normalised visceral sensitivity and SP immunolabelling, but
      not intestinal microbiota counts. CONCLUSION: Perturbations in gut flora and in
      inflammatory cell activity alter sensory neurotransmitter content in the colon,
      and result in altered visceral perception. Changes in gut flora may be a basis
      for the variability of abdominal symptoms observed in functional gastrointestinal
      disorders and may be prevented by specific probiotic administration.

PMID- 16105891
TI  - Cholera toxin subunit B inhibits IL-12 and IFN-{gamma} production and signaling
      in experimental colitis and Crohn's disease.
AB  - BACKGROUND AND AIMS: Cholera toxin B subunit (CT-B) is a powerful modulator of
      immune responses. The authors have previously demonstrated that oral
      administration of recombinant CT-B (rCT-B) is able to prevent and cure the
      Crohn's disease (CD)-like trinitrobenzene sulfonic acid (TNBS) mediated colitis.
      In this study they extended their observations and examined if rCT-B interferes
      with the molecular signaling underlying the Th1 type response both in TNBS
      colitis and in ex vivo human CD explants. METHODS: TNBS treated mice were fed
      with rCT-B, and IFN-gamma and IL-12 production by colonic lamina propria
      mononuclear cells (LPMC) was examined by ELISA. In vitro culture of mucosal
      explants from CD patients and non-inflammatory bowel disease controls, pre
      incubated with rCT-B, were examined for IFN-gamma and IL-12 production by ELISA
      and semiquantitative reverse transcription polymerase chain reactions. STAT-1, 
      4, -6 activation and T-bet expression were examined following rCT-B treatment by
      western blotting both in TNBS treated mice and in human mucosal explants.
      RESULTS: rCT-B significantly reduced IL-12 and IFN-gamma secretion by LPMC from
      TNBS treated mice. Consistent with this, rCT-B inhibited both STAT-4 and STAT-1
      activation and downregulated T-bet expression. Inhibition of Th1 signaling by CT
      B associated with no change in IL-4 synthesis and expression of active STAT-6
      indicating that rCT-B does not enhance Th2 cell responses. Moreover, in vitro
      treatment of CD mucosal explants with rCT-B resulted in reduced secretion of IL
      12/IFN-gamma and inhibition of STAT-4/STAT-1 activation and T-bet expression.
      CONCLUSIONS: These studies indicate that CT-B inhibits mucosal Th1 cell signaling
      and suggest that rCT-B may be a promising candidate for CD therapy.

PMID- 16105892
TI  - Radiation dose to family members of hyperthyroidism and thyroid cancer patients
      treated with 131I.
AB  - The thermoluminescence dosemeter (TLD) was used for measuring radiation dose to
      family members of thyrotoxicosis and thyroid cancer patients treated with (131)I
      using CaSO(4):Dy discs. There were 45 family members of thyrotoxicosis patients,
      who were divided into two groups with 22 in the first and 23 in the second group.
      Radiation safety instructions were the same for both the groups except in the
      second group where the patients were advised to use a separate bed at home for
      the first 3 d of dose administration. An activity ranging from 185 to 500 MBq was
      administered to these patients. The whole-body dose to family members ranged from
      0.4 to 2.4 mSv (mean 1.1 mSv) in the first group and 0-1.9 mSv (mean 0.6 mSv) in
      the second group. A total of 297 family members of thyroid cancer patients were
      studied for whole-body dose estimation. An activity ranging from 0.925 to 7.4 GBq
      was administered to the thyroid cancer patients. The family members were divided
      into three groups depending upon the mode of transport and facilities available
      at home to avoid close proximity with the patient. Group A with 25 family members
      received a dose ranging from 0 to 0.9 mSv (mean 0.4 mSv), group B with 96 family
      members received a dose ranging from 0 to 8.5 mSv (mean 0.8 mSv) and group C with
      176 family members received a dose ranging from 0 to 5.0 mSv (mean 0.8 mSv). The
      thyroid monitoring was also done in 103 family members who attended the patients
      in isolation wards for >2 d. Thyroid dose in them ranged from 0 to 2.5 mGy (mean
      0.1 mGy).

PMID- 16105893
TI  - Dose estimation by EPR spectroscopy of tooth enamel in Chinese medical diagnostic
      X-ray workers.
AB  - Individual accumulated doses were determined by electron paramagnetic resonance
      spectroscopy of tooth enamel in Chinese medical diagnostic X-ray workers. Dose
      determination was performed using a specially developed automatic spectrum
      processing procedure. The determined dose values owing to X rays for the three
      workers with entry year (the year they began their career as medical diagnostic X
      ray workers) in the 1950s ranged from 435 to 903 mGy, the converted effective
      doses ranged from 91 to 190 mSv.

PMID- 16105894
TI  - Distribution of naturally occurring radionuclides in soils of the southern
      districts of Bangladesh.
AB  - The activity concentrations of naturally occurring radioactive materials in soil
      samples of an elevated radiation background area of nine southern districts of
      Bangladesh were determined using gamma-ray spectrometry with an aim of evaluating
      the environmental radioactivity. The outdoor and indoor external effective dose
      rates and the radiation hazard indices from the soil activity were evaluated with
      an aim of minimising the harmful effects of ionising radiation to the population
      of the area concerned. The activity of (137)Cs was measured and observed in some
      of the locations.

PMID- 16105895
TI  - The impact of the draft 2005 recommendations of ICRP on secondary derived
      regulatory values being considered by the US Department of Energy.
AB  - The US Department of Energy, Office of Environment, Safety and Health, Office of
      Health is responsible for maintaining the Department of Energy's occupational
      radiation protection rule, Title 10 Code of Federal Regulations, Part 835,
      Occupational Radiation Protection. The Department of Energy is evaluating
      amending its rule to include the dose assessment methodology recommended in
      International Commission on Radiological Protection (ICRP) Publications 60 and
      68. On 21 June 2004 the ICRP posted their draft, Recommendations of the
      International Commission on Radiological Protection 2005, which included
      revisions to the recommended dose assessment methodology. The Department of
      Energy compared the draft recommendations to determine their effect on the
      changes the Department of Energy is currently considering.

PMID- 16105896
TI  - Oligonucleotide properties determination and primer designing: a critical
      examination of predictions.
AB  - MOTIVATION: Precise prediction of melting temperature (T(m)), secondary
      structures and design of oligonucleotides determine the efficiency and success of
      experimentation in molecular biology. Availability of a plethora of software and
      the users unawareness about their limitations compromises the accuracy and
      reliability of the predictions. RESULTS: Comparative analysis of 56 modules was
      done for T(m) prediction using a large set of oligonucleotide sequences spanning
      the whole range of GC-content and length. Allawi module of the calculator
      'MELTING', Nearest Neighbor (NN) of oligo calculator (McLab), NN of T(m)
      Calculation for Oligos (Biomath Calculator, Promega) and HYTHER provided the most
      precise T(m) predictions. A model has also been proposed to calculate the optimum
      annealing temperature integrating the already reported formulations. Secondary
      structure predictions of oligonucleotides reveal a large number of structures in
      contrast to the experimental observations. Of the 11 primer designing tools
      evaluated, Primer 3 and WebPrimer performed the best for the AT-rich templates,
      Exon Primer for AT = GC templates, and Primer Design Assistant, Primer3 and
      Primer Quest for GC-rich templates. This study provides optimal choice for
      application to the user, increasing the success of a variety of experimentations,
      especially those that have high-throughput and complex assay designs. CONTACT:
      db@igib.res.in SUPPLEMENTARY INFORMATION: The details of the oligonucleotides and
      of the different modules of T(m) prediction considered for the study are provided
      as Supplementary Information, available at Bioinformatics online.

PMID- 16105897
TI  - Simple decision rules for classifying human cancers from gene expression
      profiles.
AB  - MOTIVATION: Various studies have shown that cancer tissue samples can be
      successfully detected and classified by their gene expression patterns using
      machine learning approaches. One of the challenges in applying these techniques
      for classifying gene expression data is to extract accurate, readily
      interpretable rules providing biological insight as to how classification is
      performed. Current methods generate classifiers that are accurate but difficult
      to interpret. This is the trade-off between credibility and comprehensibility of
      the classifiers. Here, we introduce a new classifier in order to address these
      problems. It is referred to as k-TSP (k-Top Scoring Pairs) and is based on the
      concept of 'relative expression reversals'. This method generates simple and
      accurate decision rules that only involve a small number of gene-to-gene
      expression comparisons, thereby facilitating follow-up studies. RESULTS: In this
      study, we have compared our approach to other machine learning techniques for
      class prediction in 19 binary and multi-class gene expression datasets involving
      human cancers. The k-TSP classifier performs as efficiently as Prediction
      Analysis of Microarray and support vector machine, and outperforms other learning
      methods (decision trees, k-nearest neighbour and naive Bayes). Our approach is
      easy to interpret as the classifier involves only a small number of informative
      genes. For these reasons, we consider the k-TSP method to be a useful tool for
      cancer classification from microarray gene expression data. AVAILABILITY: The
      software and datasets are available at http://www.ccbm.jhu.edu CONTACT:
      actan@jhu.edu.

PMID- 16105898
TI  - MESHI: a new library of Java classes for molecular modeling.
AB  - Adapting a modular and object-oriented approach in the design of molecular
      modeling packages may reduce the software development barrier between ideas and
      their programed applications. Towards this goal we developed MESHI, a new,
      strictly object-oriented, molecular modeling suite written in Java. MESHI
      provides a comprehensive library of extendable classes for all the essential
      components of molecular modeling: molecular and geometry elements, energy
      functions and optimization methods. AVAILABILITY: MESHI and its related
      documentation are freely available at http://www.cs.bgu.ac.il/~meshi; the MESHI
      API is available at http://www.cs.bgu.ac.il/~meshi/API CONTACT:
      keasar@cs.bgu.ac.il SUPPLEMENTARY INFORMATION: The Supplementary information
      includes (1) a detailed description of several key packages and classes, and (2)
      a brief presentation of results achieved by using the MESHI application--Beautify
      -in the CASP6 experiment.

PMID- 16105899
TI  - Combining phylogenetic motif discovery and motif clustering to predict co
      regulated genes.
AB  - MOTIVATION: We present a sequence-based framework and algorithm PHYLOCLUS for
      predicting co-regulated genes. In our approach, de novo discovery methods are
      used to find motifs conserved by evolution and then a Bayesian hierarchical
      clustering model is used to cluster these motifs, thereby grouping together genes
      that are putatively co-regulated. Our clustering procedure allows both the number
      of clusters and the motif width within each cluster to be unknown. RESULTS: We
      use our framework to predict co-regulated genes in the bacterium Bacillus
      subtilis using six other closely related bacterial species. Our predicted motifs
      and gene clusters are validated using several external sources and significant
      clusters are examined in detail. An extension to the discovery and clustering of
      two-block motifs can be used for inference about synergistic binding
      relationships between transcription factors. AVAILABILITY: Software and
      Supplementary Materials can be downloaded at
      http://stat.wharton.upenn.edu/~stjensen/research/phyloclus.html or
      http://www.fas.harvard.edu/~junliu/phyloclus.html CONTACT:
      stjensen@wharton.upenn.edu.

PMID- 16105900
TI  - Statistical evaluation of pairwise protein sequence comparison with the Bayesian
      bootstrap.
AB  - MOTIVATION: Protein sequence comparison methods are routinely used to infer the
      intricate network of evolutionary relationships found within the rapidly growing
      library of protein sequences, and thereby to predict the structure and function
      of uncharacterized proteins. In the present study, we detail an improved
      statistical benchmark of pairwise protein sequence comparison algorithms. We use
      bootstrap resampling techniques to determine standard statistical errors and to
      estimate the confidence of our conclusions. We show that the underlying structure
      within benchmark databases causes Efron's standard, non-parametric bootstrap to
      be biased. Consequently, the standard bootstrap underpredicts average performance
      when used in the context of evaluating sequence comparison methods. We have
      developed, as an alternative, an unbiased statistical evaluation based on the
      Bayesian bootstrap, a resampling method operationally similar to the standard
      bootstrap. RESULTS: We apply our analysis to the comparative study of amino acid
      substitution matrix families and find that using modern matrices results in a
      small, but statistically significant improvement in remote homology detection
      compared with the classic PAM and BLOSUM matrices. AVAILABILITY: The sequence
      sets and code for performing these analyses are available from
      http://compbio.berkeley.edu/. CONTACT: brenner@compbio.berkeley.edu.

PMID- 16105901
TI  - Bias in the estimation of false discovery rate in microarray studies.
AB  - MOTIVATION: The false discovery rate (FDR) provides a key statistical assessment
      for microarray studies. Its value depends on the proportion pi(0) of non
      differentially expressed (non-DE) genes. In most microarray studies, many genes
      have small effects not easily separable from non-DE genes. As a result, current
      methods often overestimate pi(0) and FDR, leading to unnecessary loss of power in
      the overall analysis. METHODS: For the common two-sample comparison we derive a
      natural mixture model of the test statistic and an explicit bias formula in the
      standard estimation of pi(0). We suggest an improved estimation of pi(0) based on
      the mixture model and describe a practical likelihood-based procedure for this
      purpose. RESULTS: The analysis shows that a large bias occurs when pi(0) is far
      from 1 and when the non-centrality parameters of the distribution of the test
      statistic are near zero. The theoretical result also explains substantial
      discrepancies between non-parametric and model-based estimates of pi(0).
      Simulation studies indicate mixture-model estimates are less biased than standard
      estimates. The method is applied to breast cancer and lymphoma data examples.
      AVAILABILITY: An R-package OCplus containing functions to compute pi(0) based on
      the mixture model, the resulting FDR and other operating characteristics of
      microarray data, is freely available at http://www.meb.ki.se/~yudpaw CONTACT:
      yudi.pawitan@meb.ki.se and alexander.ploner@meb.ki.se.

PMID- 16105902
TI  - Complex networks approach to gene expression driven phenotype imaging.
AB  - MOTIVATION: The need is to visualize and quantify gene expression spatial
      patterns. Because of their generality for representation of interaction among
      several elements, complex networks are used to measure the spatial interactions
      and adjacencies defined by gene expression patterns. RESULTS: Enhanced
      visualization of spatial interactions between elements where genes are expressed
      is possible, allowing the identification of structures which would go unnoticed
      by using conventional imaging. The quantification of the expression intensity in
      terms of the node degree and clustering coefficient allows the identification of
      different types of interactions, yielding insights about cell signaling and
      differentiation, and providing the basis for comparison and discrimination of the
      patterns along the developmental stages. AVAILABILITY: Supplementary Material,
      including visualizations as well as the basic routines for translating gene
      expression images into complex networks and obtaining node degree and clustering
      coefficient measurements, are provided. CONTACT: luciano@if.sc.usp.br;
      diambra@univap.br.

PMID- 16105903
TI  - Robust accurate identification of peptides (RAId): deciphering MS2 data using a
      structured library search with de novo based statistics.
AB  - MOTIVATION: The key to MS -based proteomics is peptide sequencing. The major
      challenge in peptide sequencing, whether library search or de novo, is to better
      infer statistical significance and better attain noise reduction. Since the noise
      in a spectrum depends on experimental conditions, the instrument used and many
      other factors, it cannot be predicted even if the peptide sequence is known. The
      characteristics of the noise can only be uncovered once a spectrum is given. We
      wish to overcome such issues. RESULTS: We designed RAId to identify peptides from
      their associated tandem mass spectrometry data. RAId performs a novel de novo
      sequencing followed by a search in a peptide library that we created. Through de
      novo sequencing, we establish the spectrum-specific background score statistics
      for the library search. When the database search fails to return significant
      hits, the top-ranking de novo sequences become potential candidates for new
      peptides that are not yet in the database. The use of spectrum-specific
      background statistics seems to enable RAId to perform well even when the spectral
      quality is marginal. Other important features of RAId include its potential in de
      novo sequencing alone and the ease of incorporating post-translational
      modifications.

PMID- 16105904
TI  - NdPASA: a pairwise sequence alignment server for distantly related proteins.
AB  - SUMMARY: NdPASA is a web server specifically designed to optimize sequence
      alignment between distantly related proteins. The program integrates structure
      information of the template sequence into a global alignment algorithm by
      employing neighbor-dependent propensities of amino acids as a unique parameter
      for alignment. NdPASA optimizes alignment by evaluating the likelihood of a
      residue pair in the query sequence matching against a corresponding residue pair
      adopting a particular secondary structure in the template sequence. NdPASA is
      most effective in aligning homologous proteins sharing low percentage of sequence
      identity. The server is designed to aid homologous protein structure modeling. A
      PSI-BLAST search engine was implemented to help users identify template
      candidates that are most appropriate for modeling the query sequences.

PMID- 16105905
TI  - Screening of TP53 mutations by DHPLC and sequencing in brain tumours from
      patients with an occupational exposure to pesticides or organic solvents.
AB  - The aetiology of brain tumours remains unclear. Occupational exposures to
      pesticides and organic solvents are suspected risk factors. The case-control
      study CEREPHY (221 cases, 442 controls) carried in the Departement de la Gironde
      in France revealed a significantly increased risk of brain tumours for subjects
      most exposed to pesticides. In some cancers, TP53 mutations could reflect
      exposure to specific carcinogens. These mutations are present in approximately
      30% of astrocytic brain tumours. In a pilot study, we explored the hypothesis
      that pesticide or solvent exposure could raise the frequency of TP53 mutations in
      brain tumour cells. We investigated TP53 mutations in exons 2-11 by denaturing
      high performance liquid chromatography (DHPLC) and sequencing, and p53
      accumulation by immunohistochemistry in brain tumour of the 30 patients from
      CEREPHY study with a history of occupational exposure to pesticides (n = 21)
      and/or organic solvents (n = 14) for whom tumoral tissue was available. Included
      cases concerned 27% of CEREPHY cases exposed to pesticides and, based on the
      cumulative index of occupational exposure, they were more exposed to pesticides.
      There were 12 gliomas, 6 meningiomas, 7 neurinomas, 2 central nervous system
      lymphomas and 3 tumours of other histological types. We detected TP53 mutations
      in three tumours, which is similar to the expected number (3.3) calculated from
      46 published studies referenced in the IARC TP53 mutations database, taking into
      account histological types. Considering TP53 mutations previously detected in the
      laboratory by DHPLC and the frequency of TP53 polymorphisms detected in this
      sample (similar to published data), the TP53 mutations rate is probably not
      underestimated. These preliminary results, even if it was on a limited number of
      tumours, are not in favour of the role of pesticide or organic solvent exposure
      in the occurrence of TP53 mutations in brain tumours.

PMID- 16105906
TI  - Mutagen sensitivity of patients with cancer at different sites of the head and
      neck.
AB  - In the aetiology of head and neck squamous cell carcinoma (HNSCC), smoking and
      heavy alcohol consumption are the main environmental risk factors. The bleomycin
      (BLM) sensitivity assay is believed to measure environment-related cancer risks,
      mainly of HNSCC. Previously, we have shown that this method is only moderately
      sensitive to identify individuals at high risk for developing HNSCC, due to broad
      overlap of BLM-induced chromatid breaks per cell (b/c) between cancer patients
      and controls, and alcoholics with liver diseases. In the present study, we
      evaluated whether the differences between patients and controls are more
      manifested when the risks according to localization of HNSCC are examined. BLM
      sensitivity in lymphocytes of 278 patients with HNSCC at four different
      anatomical sites, and that of 356 frequency-matched controls was studied. There
      was a significant difference in BLM-induced b/c values between patients (1.11
      b/c) and controls (0.97 b/c); however, considering all HNSCC cases, only 58.3% of
      patients and 43.3% of controls were mutagen sensitive. When the patients were
      distributed according to tumour sites, mutagen sensitivity of those with cancer
      of oral cavity, oropharynx and hypopharynx was significantly higher than that of
      the frequency-matched controls (1.12-1.14 b/c versus 1.00 b/c), while laryngeal
      tumour patients (1.05 b/c) did not differ from controls (1.00 b/c). When the
      associations between BLM sensitivity and the risk of HNSCC sites were examined,
      it was expressed mostly in patients with tumours of the oral cavity and
      oropharynx (OR = 1.97 and OR = 1.90), and not in patients with tumours of the
      hypopharynx and larynx. Though the mutagen sensitivity decreased from the oral
      cavity down to the larynx, indicating that the site-specific risks may differ,
      the BLM assay shows weak and controversial associations between mutagen
      sensitivity and cancer risk of patients even at specific HNSCC sites.

PMID- 16105907
TI  - Spontaneous pneumothorax associated with ankylosing spondylitis.
AB  - OBJECTIVE: To review the incidence and clinical characteristics of spontaneous
      pneumothorax in patients with ankylosing spondylitis (AS). METHODS: This is a
      retrospective observational cohort study. Chest radiographs and medical records
      of patients with a diagnosis of AS from 1993 to 2003 in a tertiary referral
      centre were reviewed. RESULTS: A total of 1028 patients with a diagnosis of AS
      were identified from July 1993 to July 2003. Twenty-two patients had typical
      apical lung fibrotic changes in the chest radiographs (22/1028, 2.1%). Three of
      these patients (3/22, 13.6%) with lung disease had pneumothorax. Two patients had
      recurrences and received video-assisted thoracoscopic surgery (VATS) on the
      second attack. The third patient received talc pleurodesis on the first attack
      and did not have a recurrence. The incidence of spontaneous pneumothorax in
      patients with AS was 0.29% (3/1028) with an incidence density of 64.85/100,000
      patient-yr (95% confidence interval: 66.17-63.57/100,000). CONCLUSION:
      Spontaneous pneumothorax appears to be exceedingly rare in AS unless there is an
      underlying fibrocystic lung disease, in which case its occurrence is not
      uncommon. Cigarette smoking may be an important co-factor. Once developed,
      recurrences are common even after treatment. Prophylactic procedures should thus
      be considered for the first attack of spontaneous pneumothorax.

PMID- 16105908
TI  - Extremely high titer of anti-human chimeric antibody following re-treatment with
      rituximab in a patient with active systemic lupus erythematosus.

PMID- 16105909
TI  - Potential failure of contraceptive efficacy in a patient taking methotrexate.

PMID- 16105910
TI  - Beneficial effects of steroid therapy for Mikulicz's disease.

PMID- 16105911
TI  - Citrullination of fibronectin in rheumatoid arthritis synovial tissue.
AB  - OBJECTIVES: Citrullination, catalysed by peptidylarginine deiminase (PAD), is the
      post-translational modification of peptidylarginine to citrulline, which is
      intimately involved in the pathogenesis of rheumatoid arthritis (RA). Fibronectin
      (Fn), a large glycoprotein, is expressed at high levels in arthritic joints and
      it mediates various physiological processes through interactions with cell
      surface integrin receptors and growth factors. We investigated the citrullination
      of Fn and its potential contribution to the pathogenesis of RA. METHODS: We
      localized Fn expression and citrullination in RA synovial tissue by
      immunohistochemistry, immunoprecipitation and western blotting. We also
      determined levels of citrullinated Fn in plasma from RA patients using sandwich
      enzyme-linked immunosorbent assay (ELISA). After incubating Fn with rabbit
      skeletal muscle PAD, we examined the binding ability of citrullinated Fn to
      vascular endothelial growth factor (VEGF) and integrin beta1 using a solid-phase
      receptor binding assay as well as the effect of the citrullinated Fn on apoptosis
      using cultured HL-60 cells. RESULTS: Immunohistochemistry and western blotting
      analysis indicated that Fn formed extracellular aggregates that were specifically
      citrullinated in RA synovial tissue. No Fn deposits were observed in synovial
      tissues of osteoarthritis (OA). Sandwich ELISA detected higher levels of
      citrullinated Fn in plasma from patients with RA than from healthy controls or
      those with systemic lupus erythematosus. Following citrullination in vitro, the
      affinity of Fn for VEGF increased, but binding activity to integrin beta1
      decreased and Fn no longer stimulated the apoptosis of monocytes induced from
      cultured HL-60 cells. CONCLUSIONS: Our results suggest that the citrullination of
      Fn is a specific event for RA synovium, although others have detected
      citrullinated total proteins in inflamed synovial tissue of RA and non-RA
      patients. Citrullination of Fn could alter interactions between Fn and its
      receptors and growth factors, consequently contributing to mechanisms of RA
      pathogenesis such as perturbed angiogenesis and apoptosis.

PMID- 16105912
TI  - Hepatomegaly as a rare presentation of Churg-Strauss syndrome.

PMID- 16105913
TI  - The unmet need for anti-tumour necrosis factor (anti-TNF) therapy in ankylosing
      spondylitis.
AB  - OBJECTIVES: Anti-tumour necrosis factor (anti-TNF) therapy is effective in the
      treatment of ankylosing spondylitis (AS), but guidelines are needed because of
      the cost. The primary aim of this study was to evaluate the proportion of
      patients with AS who meet the criteria for anti-TNF therapy as well as to explore
      the relationship between disease activity, health status and quality of life in
      patients with AS who would potentially meet the criteria compared with those who
      would not. METHODS: All patients with a confirmed diagnosis of AS were identified
      via a search through the clinic correspondence database and sent postal
      questionnaires. Data captured included demographics, disease activity, aspects of
      functional impairment, activity limitation and quality of life using the Bath
      Ankylosing Spondylitis Disease Activity Index (BASDAI), pain scores (using a
      visual analogue scale), the Bath Ankylosing Spondylitis Functional Index (BASFI),
      Health Assessment Questionnaire (HAQ), short-form 36 (SF-36) and the Ankylosing
      Spondylitis Quality of Life (ASQoL) questionnaire. The unpaired Student's t-test,
      chi(2) test and Mann-Whitney U-test were performed for comparisons of groups
      where appropriate. RESULTS: Out of 325 mailed questionnaires, 246 (76%) were
      returned. The mean age of the patients who replied to the questionnaire was 52 yr
      (+/-12 yr) and 25% (62) were females. Mean BASDAI was 49 (+/-24) and 64% had a
      BASDAI > or = 40. There were significant differences between the groups with a
      BASDAI above and below 40 in pain by VAS, functional ability (BASFI, HAQ), health
      status (SF-36) and quality of life (ASQoL). Almost two-thirds (64%) of patients
      would meet the criteria for anti-TNF therapy under recommended guidelines.
      CONCLUSION: Patients with AS demonstrated poor functional status and poor quality
      of life. There is a large unmet need for effective therapy in AS, with almost two
      thirds of patients meeting the proposed criteria for biological therapy. Patients
      with a BASDAI > or = 40 had a worse functional status and quality of life than
      those who have a BASDAI of <40. These results indicate that the need for
      effective intervention for AS is a priority area.

PMID- 16105914
TI  - Management of rheumatoid arthritis in primary care--an educational need?

PMID- 16105915
TI  - Cryoplasty for the treatment of femoropopliteal arterial disease: will freezing
      solve the problem of cold feet?

PMID- 16105916
TI  - SIR 2005 film panel case: heterotaxia with polysplenia.

PMID- 16105917
TI  - SIR 2005 film panel case: peripheral embolization from cardiac myxoma.

PMID- 16105918
TI  - Cryoplasty for the treatment of femoropopliteal arterial disease: results of a
      prospective, multicenter registry.
AB  - PURPOSE: Despite suboptimal results, angioplasty of femoropopliteal arterial
      lesions has been a mainstay of endovascular therapy for many years. The recent
      introduction of cryoplasty marks a potential advance in the ability to
      effectively treat peripheral arterial atherosclerotic stenoses. This article
      presents the results of a prospective, multicenter trial that evaluated the
      efficacy of cryoplasty for femoropopliteal disease. MATERIALS AND METHODS: One
      hundred two patients with claudication and lesions of the superficial femoral and
      popliteal arteries of no greater than 10 cm were studied. All patients were
      treated with a primary strategy of stand-alone cryoplasty with use of the
      PolarCath cryoplasty system. The primary endpoints of the study were acute
      technical success and clinical patency at 9 months. Technical success was defined
      as the ability to achieve residual angiographic stenosis no greater than 30% and
      residual stenosis less than 50% by duplex ultrasound (US) imaging. Clinical
      patency was defined as freedom from target lesion revascularization within 9
      months. Primary patency was defined by a duplex US systolic velocity ratio no
      greater than 2.0. RESULTS: A total of 102 patients were enrolled at 16 centers.
      Of those treated, 31% had diabetes and 31% were active cigarette smokers. The
      majority of the lesions were confined to the superficial femoral artery (84.3%)
      and 14.7% presented with total occlusions. The mean vessel diameter treated was
      5.5 mm +/- 0.5, the mean stenosis diameter was 87% +/- 10%, and the mean lesion
      length was 4.7 cm +/- 2.6. The technical success rate was 85.3% with a mean
      residual stenosis after cryoplasty of 11.2% +/- 11.2% (P < .05 vs baseline).
      Clinical patency in this group was 82.2%, as only 16 patients required target
      lesion revascularization during the 9-month surveillance period. Primary patency
      determined by duplex US was 70.1%. CONCLUSIONS: Cryoplasty demonstrated a high
      degree of acute angiographic success and a low frequency of target lesion
      revascularization. The patency rate observed compares favorably to that
      previously documented with conventional angioplasty.

PMID- 16105919
TI  - A phase I trial of alfimeprase for peripheral arterial thrombolysis.
AB  - PURPOSE: To evaluate the safety profile, pharmacokinetics, and thrombolytic
      activity of alfimeprase, a novel direct-acting thrombolytic agent, in patients
      with chronic peripheral arterial occlusion (PAO). MATERIALS AND METHODS: In this
      multicenter, open-label, single-dose, dose-escalation study, 20 patients with
      worsening symptoms of lower extremity ischemia within 6 months of enrollment were
      treated with alfimeprase in five escalating dose cohorts (0.025 mg/kg, 0.05
      mg/kg, 0.1 mg/kg, 0.3 mg/kg, and 0.5 mg/kg) by means of intraarterial and
      sometimes intrathrombic pulsed infusion. The primary endpoint was safety assessed
      by adverse event rates. Additional safety assessments included vital sign
      monitoring, serum chemistry testing, hematologic testing, and coagulation testing
      for 28 days after the procedure, as well as alpha2-macroglobulin and
      antialfimeprase antibody testing for as long as 3 months after treatment.
      Pharmacokinetic parameters were evaluated with use of an assay that measures free
      and alpha2-macroglobulin-bound (ie, total) alfimeprase. RESULTS: No patient
      experienced a hemorrhagic adverse event. Mean plasminogen and fibrinogen
      concentrations were not substantially altered by treatment. Three transient
      treatment-related adverse events were reported in the same patient: one incidence
      each of increased blood fibrinogen level, skin rash, and headache. All three
      adverse events were graded as mild. The pharmacokinetic profile of alfimeprase
      suggested that the half-life for total alfimeprase ranges from 11 to 54 minutes
      (median, 25 min) in patients with PAO. The serum alpha2-macroglobulin
      concentrations decreased transiently in a dose response-like manner between 12
      and 24 hours and returned to within normal limits approximately 14 days after
      alfimeprase exposure. CONCLUSIONS: Alfimeprase in doses as high as 0.5 mg/kg was
      generally well-tolerated in patients with chronic PAO. No bleeding complications
      were noted. The stable fibrinogen concentrations suggest that the activity of
      alfimeprase may be limited to the target thrombus. Alfimeprase holds the
      potential to achieve dissolution of thrombus with a diminished risk of
      hemorrhage.

PMID- 16105920
TI  - The effect of catheter-directed CT angiography on yttrium-90 radioembolization
      treatment of hepatocellular carcinoma.
AB  - PURPOSE: Yttrium 90 radioembolization is a transcatheter therapy for unresectable
      hepatocellular carcinoma (HCC) that delivers internal radiation to tumors. In
      contrast to the usual method of lobar regional delivery, catheter-directed
      computed tomographic (CT) angiography was investigated as a potentially useful
      technique to evaluate the administration of segmental 90Y tumor radiation doses
      superselectively without significantly altering liver function or Child-Pugh
      classification. MATERIALS AND METHODS: Fourteen patients underwent 90Y therapy
      for unresectable HCC. After standard angiographic placement of a 3-F
      microcatheter in a segmental hepatic artery supplying the tumor, each patient
      underwent CT angiography with use of segmental hepatic artery injection of
      iodinated contrast agent to confirm segmental perfusion and delineate segmental
      liver volume. 90Y was later injected into the same segmental artery. Target dose
      was calculated according to infused 90Y activity and targeted hepatic volume with
      standard lobar volume (before CT angiography) versus segmental liver volume
      (after CT angiography). The Wilcoxon signed-rank test (alpha = 0.05) was used to
      compare the estimated 90Y dose before CT angiography with the actual 90Y dose
      after CT angiography, as well as changes in serum bilirubin level and Child-Pugh
      classification as a result of treatment. RESULTS: The mean estimated tumor dose
      before CT angiography (SD) was 100 Gy +/- 43 (range, 35-169 Gy). The mean actual
      tumor dose after CT angiography was 348 Gy +/- 204 (range, 105-857 Gy), which was
      significantly greater (P < .001). The mean bilirubin level before treatment was
      1.0 mg/dL +/- 0.97 (range, 0.2-4.0 mg/dL), whereas the mean bilirubin level after
      treatment was 1.3 mg/dL +/- 0.85 (range, 0.5-3.8 mg/dL). This difference,
      although statistically significant (P = .03), was not clinically important.
      Thirteen of 14 patients had no change in Child-Pugh class. CONCLUSION: CT
      angiography can be used to delineate the blood supply and volume to a targeted
      hepatic segment, allowing superselective 90Y radioembolization. This approach
      significantly increases effective 90Y tumor radiation dose without clinically
      altering liver function or Child-Pugh class.

PMID- 16105921
TI  - Pain and quality of life assessment after endovascular versus open repair of
      abdominal aortic aneurysms in patients at low risk.
AB  - PURPOSE: To compare functional autonomy, quality of life (QOL), and pain control
      after endovascular and open repair (OR) of abdominal aortic aneurysms. MATERIALS
      AND METHODS: Forty patients with a low surgical risk profile and anatomic
      compatibility for stent-graft therapy were randomized to receive OR or
      endovascular aneurysm repair (EVAR). Technical and clinical success as well as
      mortality were assessed in both groups and compared by Kaplan-Meier analysis.
      Functional autonomy and QOL were assessed by Karnofsky score and Short Form 36
      (SF-36) questionnaire. Pain control was assessed by a numeric rating scale and
      Brief Pain Inventory questionnaire. QOL outcomes by means of the SF-36 and pain
      questionnaires were compared with use of mixed-effects models for repeated
      measures analysis. RESULTS: All procedures were technically successful in both
      groups. Three late clinical failures requiring surgical conversion or repeated
      intervention were observed in the EVAR group and one was observed in the OR
      group. There was no significant difference between groups in terms of functional
      autonomy or QOL. No difference in pain level was evident during the early
      postoperative period, whereas the pain level was lower in the OR group after 1
      month. Opioid analgesic drug consumption was significantly greater in the OR
      group during the postoperative period. Mean hospitalization duration was shorter
      in the EVAR group than in the OR group (4.5 days +/- 2.4 vs 11.5 days +/- 8.1; P=
      .001). CONCLUSION: EVAR has no advantage over OR in patients at low risk in terms
      of functional autonomy, QOL, and pain control. However, EVAR was associated with
      shorter hospitalization durations compared with OR.

PMID- 16105922
TI  - Reduction of metastatic load to liver after intraarterial hepatic yttrium-90
      radioembolization as evaluated by [18F]fluorodeoxyglucose positron emission
      tomographic imaging.
AB  - PURPOSE: To assess the response of hepatic metastases after treatment with
      intraarterial yttrium 90 radioembolization (ie, use of SIR-Spheres) with use of
      [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). MATERIALS AND
      METHODS: Nineteen patients with metastatic cancer to the liver from various solid
      tumors with progression despite polychemotherapy were included. All patients
      underwent baseline computed tomography, FDG PET, hepatic angiography, and
      intraarterial technetium 99 m macroaggregated albumin scan for assessment of lung
      shunting fraction. Patients were treated with 90Y resin microspheres on a lobar
      basis and were monitored for 3 months with use of dedicated attenuation-corrected
      PET. For each patient, regions of interest were drawn along the liver edge to
      measure total liver standard uptake value (SUV) on axial images, covering the
      entire liver. Visual estimates were also performed and graded as +1, 0, -1, -2,
      or -3 for progression, no change, and mild, moderate, and dramatic improvement by
      posttreatment PET. RESULTS: The median absorbed dose for the tumor was 76 Gy.
      There was a significant overall decrease in total liver SUV after treatment
      (baseline, 71,134 +/- 38,055; after SIR-Sphere treatment, 59,941 +/- 26,509; P =
      .028) for the entire group. Visual estimates placed 15 patients (79%) in response
      categories (-3 to -1) and four patients (21%) in nonresponse categories (0 to +1)
      for the liver. The percentage change of total liver SUV after treatment in the
      response group (-19%) was significantly greater and different in direction than
      that in the nonresponse group (+27%; P = .03). This percentage change was also
      correlated significantly with the respective visual estimates (r = 0.72; P <
      .0005) for each individual patient. Three patients had major complications
      related to hyperbilirubinemia (transient, n = 1; permanent, n= 2). CONCLUSIONS:
      The results suggest that there is significant reduction of hepatic metastatic
      load as evaluated objectively by PET after 90Y radioembolization for the
      treatment of unresectable metastatic disease to the liver. 90Y radioembolization
      provides encouraging results by arresting progression of metastatic cancer to the
      liver.

PMID- 16105923
TI  - The value of serial arteriography in osteosarcoma: delivery of chemotherapy,
      determination of therapy duration, and prediction of necrosis.
AB  - PURPOSE: To investigate the value of serial arteriography to assess tumor
      response, predict necrosis, and individualize the duration of a combined
      intravenous (IV) and intraarterial (IA) neoadjuvant chemotherapy protocol in
      patients with biopsy-proven high-grade osteosarcoma or malignant
      fibrohistiocytoma of bone. MATERIALS AND METHODS: Between July 1987 and March
      2003, 109 patients completed a chemotherapy protocol of neoadjuvant IV
      doxorubicin and IA cisplatin. Patients were eligible regardless of age, disease
      stage, or disease site. A minimum of three IA cycles followed by definitive
      surgery was required for inclusion in the final analysis. IA dose and duration
      were increased for tumors larger than 10 cm. Initial arteriograms were scored as
      indicating mild, moderate, or marked tumor neovascularity (TNV). Subsequent
      arteriograms were prospectively compared with the baseline image for percent
      change in TNV. Treatment continued until a maximum of five cycles were
      administered or one of three criteria were met: (i) at least 90% decrease in TNV,
      (ii) plateau of effect, or (iii) no response. RESULTS: Of 408 IA procedures, 42
      patients underwent three cycles, 53 underwent four, and 14 required five cycles
      of neoadjuvant therapy. There was a 2.5% minor complication rate. Eighty-six
      percent of patients exhibited at least 90% decrease in TNV and 82% exhibited good
      histologic response (> or =90% tumor necrosis). Serial arteriography predicted a
      good histologic response with an accuracy of 90% and a sensitivity of 97%.
      CONCLUSIONS: Serial arteriography was highly sensitive and accurately predicted
      good responses. This individually modified, dose-intensified neoadjuvant protocol
      yielded an excellent histologic response rate with minimal complications. Future
      endeavors should involve a multiinstitutional study of this unique approach.

PMID- 16105924
TI  - Ultrasound-guided adult hip injections.
AB  - PURPOSE: The authors believe that ultrasound as a primary method of image
      guidance for performing hip aspirations is underutilized, and the authors report
      their experience in performing ultrasound-guided hip injections in 358 patients,
      using a free-hand technique. MATERIALS AND METHODS: A retrospective review of all
      adult ultrasound-guided hip injections performed at the authors' institution over
      a four-year period was performed. RESULTS: Retrospective review of an ultrasound
      database revealed 358 adult hip aspirations/injections were performed at the
      authors' institution from October 2000-October 2004. All procedures were
      performed using a longitudinal, anterior approach and without the use of a needle
      guide. There were no reported cases of inadvertent vascular or femoral nerve
      puncture. CONCLUSIONS: To the authors' knowledge, this is the largest reported
      series of sonographically-guided adult hip aspirations/injections without the use
      of a needle guide. The authors believe that ultrasound as a primary method of
      image guidance for performing hip aspirations is underutilized. The absence of
      radiation and relatively short procedure time of ultrasound-guided hip injections
      are favorable factors to both the authors' referring clinician population as well
      as the patients.

PMID- 16105925
TI  - Management of central venous stent migration in a patient with a permanent
      inferior vena cava filter.
AB  - Stent embolization is a rare complication in the treatment of central venous
      stenoses in patients receiving long-term hemodialysis. The authors report a case
      of nitinol stent embolization into the right atrium in which the stent could not
      be repositioned across an indwelling permanent inferior vena cava (IVC) filter.
      The migrated stent was managed by advancing the stent to the superior margin of
      the IVC filter and then deploying a second suprarenal IVC filter to prevent
      repeat embolization.

PMID- 16105926
TI  - Dialysis needle puncture of Wallgrafts placed in polytetrafluoroethylene
      hemodialysis grafts.
AB  - This study evaluates the effect of routine venipuncture at hemodialysis on the
      durability of Wallgraft covered stents. Thirteen covered stents were placed in
      six aging, failing polytetrafluoroethylene grafts for treatment of
      pseudoaneurysms and recurrent stenoses. Four patients did not experience
      significant graft complications. One graft was ligated for an infected overlying
      skin ulcer. After surgical revision, the graft remains functional. Another
      patient experienced fraying of the stent edges and recurrence of a small
      pseudoaneurysm. Our experience suggests that the Wallgraft covered stent can
      withstand routine venipuncture at dialysis without flow-limiting stent
      distortion.

PMID- 16105927
TI  - Endovascular treatment of splenomesenteric-portal vein thromboses during
      orthotopic liver transplantation.
AB  - Extensive splanchnic venous thrombosis in patients undergoing orthotopic liver
      transplantation (OLT) continues to have a substantial impact on surgical
      complexity and perioperative morbidity and mortality rates. This report presents
      an experience in eight patients with splanchnic venous thrombosis treated by
      means of splanchnic vessel recanalization, primary stent placement, and closure
      of spontaneous competitive shunts during OLT. In all cases, portal perfusion in
      the allograft was adequate, portal hypertension was solved, and no complications
      were observed. None of the patients died during surgery or follow-up. The results
      reported here need to be confirmed in future studies.

PMID- 16105928
TI  - Primary failure of uterine artery embolization: use of magnetic resonance imaging
      to select patients for repeated embolization.
AB  - The purpose of this study was to determine if contrast material-enhanced magnetic
      resonance (MR) imaging could be used to stratify patients who have undergone
      failed primary uterine artery embolization (UAE) for repeated embolization. One
      hundred one consecutive patients who underwent UAE at a single center were
      followed prospectively and assessed for the presence of persistent contrast
      enhancement of leiomyomas on follow-up MR imaging. Among 11 of the 111 patients
      with primary clinical failure (10%), MR imaging showed persistent enhancement in
      eight. Of the eight cases of failure with continued tumor enhancement on MR
      imaging, six were treated with repeated embolization. All six patients showed
      complete symptomatic relief at 12-month follow-up. In women who have been treated
      with failed primary UAE, continued enhancement of leiomyomas on MR imaging can be
      used to identify candidates for successful repeated UAE.

PMID- 16105929
TI  - Caval perforation with bronchial communication: a rare complication of long-term
      venous access.
AB  - Superior vena cava (SVC) perforation with bronchial communication is a very rare
      complication of long-term venous access. A patient recently presented with
      erosion of a venous port catheter into a bronchus, with infusion of medications
      into the bronchus and associated SVC syndrome. A high position of the catheter
      tip against the wall of the SVC and the beveled style of cut on the catheter tip
      contributed to this complication. A unique combination of percutaneous techniques
      was helpful in managing this complication, and surgery was avoided.

PMID- 16105930
TI  - Re: Renal angiomyolipoma--long-term results after arterial embolization.

PMID- 16105931
TI  - Re: Displacement of endoscopically placed plastic biliary endoprostheses into the
      duodenum with a simple transhepatic technique.

PMID- 16105934
TI  - Inferior vena cava filter removal after 475-day implantation.

PMID- 16105936
TI  - The neurobiology of human obesity.
AB  - Earlier ideas that sympathetic nervous system activity is low in human obesity,
      contributing to weight gain through absence of sympathetically mediated
      thermogenesis, can now be discounted. The application of sympathetic nerve
      recording techniques and isotope dilution methodology quantifying
      neurotransmitter release from sympathetic nerves has established that the
      sympathetic outflows to the kidneys and skeletal muscle vasculature are activated
      in obese humans. The cause remains unclear. The adipocyte hormone, leptin,
      stimulates the sympathetic nervous system in rodents, but whether this applies in
      humans is uncertain. Cross-sectional studies suggest a quantitative link exists
      between regional sympathetic nervous tone (most notably in the kidneys) and rates
      of leptin release, but definitive studies documenting that leptin administration
      activates the human sympathetic nervous system have not been done. What might be
      the clinical implications of these new findings? The demonstration that the
      suppressed sympathetic tone characterizing many experimental models of obesity
      does not exist in human obesity weakens the case for the use of beta3-adrenergic
      agonists as thermogenic agents to facilitate weight loss. Although the neurogenic
      character of obesity-related hypertension is now established, whether
      antiadrenergic antihypertensive drugs are the preferred agents for blood pressure
      reduction has not been adequately tested. Multiple site central venous sampling,
      disclosing release of leptin into the internal jugular veins, led to the
      demonstration that the leptin gene is also expressed in the brain, in addition to
      adipocytes. Brain resistance to leptin has been inferred in human obesity, given
      that overweight is accompanied by high plasma leptin levels. The fact that the
      genes for leptin and its receptors are normally expressed in the brain in human
      obesity, and that release of leptin from the brain is actually increased, argues
      against this. Brain leptin release has the potential to override the peripheral,
      adipocyte leptin system.

PMID- 16105937
TI  - Role of leptin in obesity-related hypertension.
AB  - Obesity in humans causes hypertension, myocardial hypertrophy and coronary
      atherosclerosis, and increased cardiovascular morbidity and mortality that is
      thought to be related to sympathetic overactivity. Leptin is an adipocyte-derived
      hormone that acts in the hypothalamus to regulate appetite, energy expenditure
      and sympathetic nervous system outflow. One of the major mechanisms leading to
      the development of obesity-induced hypertension appears to be leptin-mediated
      sympatho-activation. Leptin adversely shifts the renal pressure-natriuresis
      curve, leading to relative sodium retention. Although obesity is generally
      associated with resistance to the anorexic and weight-reducing actions of leptin,
      our work has shown preservation of its sympatho-excitatory and pressor actions.
      This selective leptin resistance of obesity, coupled with hyperleptinaemia, may
      play a critical role in the cardiovascular complications of obesity. Increased
      information about leptin and its mechanisms of actions should help the
      development of safe and effective pharmacological treatments of obesity and
      obesity-related hypertension.

PMID- 16105938
TI  - Central and peripheral contributions to obesity-associated hypertension: impact
      of early overnourishment.
AB  - Obesity induced by a high-fat diet was associated with increased tail-cuff blood
      pressure in adult rats. The mechanisms underlying obesity-related hypertension
      are unclear, but increased sympathetic activation most probably plays a role.
      Neuroendocrine alterations observed in obesity may influence both feeding
      patterns and blood pressure. Work from our laboratory has shown that chronic
      overfeeding in rats leads to changes in neuropeptide Y (NPY) and alpha-melanocyte
      stimulating hormone (alphaMSH) in the hypothalamus. These peptides have central
      effects on blood pressure, indicating that obesity-related changes in the CNS may
      impact on cardiovascular function. Population studies suggest that nutrition in
      early life can influence the subsequent risk of obesity and high blood pressure.
      To examine the impact of early postnatal overnutrition on blood pressure and
      adipose-derived mediators, we adjusted rat litters to 3 or 12 pups (overnutrition
      and control, respectively). Pups raised in small litters were 15% heavier at
      weaning, and this intervention was associated with a modest elevation of blood
      pressure and body weight as adults (16 weeks). Animals raised in small litters
      had increased 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) mRNA in
      white adipose tissue as adults, which may impact on cardiovascular function.
      Adjustment of diet after weaning, to 30% fat diet or standard chow, allowed
      comparison of the impact of different periods of overnourishment. Implementation
      of a high-fat diet at weaning overcame the effect of litter size on body weight
      from 10 weeks of age. Blood pressure rose progressively with high-fat feeding and
      was positively correlated with leptin and body weight. Chronic consumption of a
      high-fat diet led to marked increases in leptin and insulin and modest increases
      in blood pressure, and impacts on brain transmitters implicated in the regulation
      of both appetite and blood pressure. Overnourishment during early postnatal
      development led to profound changes in body weight at weaning, which tended to
      abate with maturation. It also led to long-term changes in some adipose-derived
      mediators, possibly increasing cardiovascular risk.

PMID- 16105939
TI  - Structural and functional evidence supporting a role for leptin in central neural
      pathways influencing blood pressure in rats.
AB  - Leptin, a peptide hormone normally associated with body weight homeostasis, is
      implicated in the generation of obesity-induced hypertension. Administration of
      leptin increases sympathetic nerve activity and blood pressure; however, the
      neural circuity involved in this pressor effect is not clearly defined. In this
      review we describe experiments in which pseudorabies virus was injected into the
      heart, kidney and the vasculature within skeletal muscle to reveal the
      distribution of neurones in the hypothalamus that project to these cardiovascular
      tissues. This distribution is compared to the well-documented distribution of
      leptin receptors. Finally we discuss microinjection studies designed to examine
      the effect of leptin, in these regions, on sympathetic nerve discharge and
      arterial blood pressure. Leptin injected directly into the ventromedial
      hypothalamus, arcuate nucleus and lateral hypothalamic area (particularly the
      perifornical area) increased lumbar sympathetic nerve activity. In addition,
      microinjection into the ventromedial hypothalamus and parvocellular
      paraventricular nucleus increased blood pressure. Our results demonstrate a
      discrete set of hypothalamic pathways that may underlie the involvement of leptin
      in obesity-induced hypertension.

PMID- 16105940
TI  - Role of Pam16's degenerate J domain in protein import across the mitochondrial
      inner membrane.
AB  - Translocation of proteins across the mitochondrial inner membrane is an essential
      process requiring an import motor having mitochondrial Hsp70 (mtHsp70) at its
      core. The J protein partner of mtHsp70, Pam18, is an integral part of this motor,
      serving to stimulate the ATPase activity of mtHsp70. Pam16, an essential protein
      having an inactive J domain that is unable to stimulate mtHsp70's ATPase
      activity, forms a heterodimer with Pam18, but its function is unknown. We set out
      to test the importance of three properties of Pam16: (i) a stable interaction
      between Pam16 and Pam18, (ii) the inability of Pam16's degenerate J domain to
      stimulate Ssc1's ATPase domain, and (iii) the innately lower stimulatory activity
      of the Pam16:Pam18 heterodimer, compared to Pam18 alone. Neither substantial
      reduction in the ability of Pam18 to stimulate Ssc1's ATPase activity, nor the
      presence of an active J domain in Pam16, had deleterious effects on cell growth,
      indicating the lack of importance of two of these biochemical properties.
      However, a stable interaction between Pam16's degenerate J domain and Pam18's J
      domain was found to be critical for function. Alterations that destabilized the
      Pam16:Pam18 heterodimer had deleterious effects on cell growth and mitochondrial
      protein import; intragenic suppressors that restored robust growth also restored
      heterodimer stability. Our results support the idea that Pam16's J-like domain
      strongly interacts with Pam18's J domain, leading to a productive interaction of
      Pam18 with mtHsp70 at the import channel.

PMID- 16105941
TI  - Genomes on the shrink.

PMID- 16105942
TI  - Regulation of a Bacillus subtilis mobile genetic element by intercellular
      signaling and the global DNA damage response.
AB  - Horizontal gene transfer contributes to the evolution of bacterial species.
      Mobile genetic elements play an important role in horizontal gene transfer, and
      characterization of the regulation of these elements should provide insight into
      conditions that influence bacterial evolution. We characterized a mobile genetic
      element, ICEBs1, in the Gram-positive bacterium Bacillus subtilis and found that
      it is a functional integrative and conjugative element (ICE) capable of
      transferring to Bacillus and Listeria species. We identified two conditions that
      promote ICEBs1 transfer: conditions that induce the global DNA damage response
      and crowding by potential recipients that lack ICEBs1. Transfer of ICEBs1 into
      cells that already contain the element is inhibited by an intercellular signaling
      peptide encoded by ICEBs1. The dual regulation of ICEBs1 allows for passive
      propagation in the host cell until either the potential mating partners lacking
      ICEBs1 are present or the host cell is in distress.

PMID- 16105943
TI  - Wild chimpanzees show population-level handedness for tool use.
AB  - Whether nonhuman primates exhibit population-level handedness remains a topic of
      considerable theoretical and empirical debate. One continued subject of
      discussion is whether evidence of population-level handedness in primates is
      confined to studies in captive animals or whether it is in both captive and wild
      subjects. Here, we report evidence of population-level handedness in wild
      chimpanzees for a tool-use task known as "termite-fishing." We subsequently
      compared the handedness for termite-fishing with other published reports on
      handedness for nut-cracking and wadge-dipping and found task-specific differences
      in handedness. Last, when combing all of the published data on tool use in wild
      chimpanzees, we show that hand preferences are heritable. Contrary to previous
      claims, our results demonstrate that population-level handedness is evident in
      wild chimpanzees and suggest that the antecedents of lateralization of function
      associated with hand use were present at least 5 million years ago, before the
      Pan-Homo split.

PMID- 16105944
TI  - Green light for gene targeting in plants.

PMID- 16105945
TI  - Synergistic induction of tissue factor by coagulation factor Xa and TNF: evidence
      for involvement of negative regulatory signaling cascades.
AB  - Enzymes of the blood coagulation pathway enhance the inflammatory response
      leading to endothelial dysfunction, accounting, in part, for the vascular
      complications occurring in sepsis and cardiovascular disease. The responses of
      endothelial cell activation include induction of the expression of tissue factor
      (TF), a membrane glycoprotein that promotes thrombosis, and of E-selectin, a cell
      adhesion molecule that promotes inflammation. In this report, we demonstrate
      synergistic interactions between the coagulation factor Xa (fXa) and the
      proinflammatory cytokines TNF, IL-1beta, and CD40L, leading to enhanced
      expression of TF and E-selectin in endothelial cells. A detailed analysis of the
      molecular pathways that could account for this activity of fXa showed that fXa
      inhibited the cytokine-induced expression of dual specificity phosphatases, MAP
      kinase phosphatase-L, -4, -5, and -7, blocking a negative regulatory effect on c
      Jun N-terminal kinase. The synergistic interaction between fXa and TNF was also
      involved in the inhibition of A20 and IkappaBalpha expression in the IkappaB
      kinase-NF-kappaB pathway. The data indicate that inhibition of negative
      regulatory signaling accounts for the amplification of cytokine-induced
      endothelial cell activation by fXa.

PMID- 16105946
TI  - Tuning in to musical rhythms: infants learn more readily than adults.
AB  - Domain-general tuning processes may guide the acquisition of perceptual knowledge
      in infancy. Here, we demonstrate that 12-month-old infants show an adult-like,
      culture-specific pattern of responding to musical rhythms, in contrast to the
      culture-general responding that is evident at 6 months of age. Nevertheless,
      brief exposure to foreign music enables 12-month-olds, but not adults, to
      perceive rhythmic distinctions in foreign musical contexts. These findings may
      indicate a sensitive period early in life for acquiring rhythm in particular or
      socially and biologically important structures more generally.

PMID- 16105947
TI  - Structure of dimeric mitochondrial ATP synthase: novel F0 bridging features and
      the structural basis of mitochondrial cristae biogenesis.
AB  - The F1F0-ATP synthase exists as a dimer in mitochondria, where it is essential
      for the biogenesis of the inner membrane cristae. How two ATP synthase complexes
      dimerize to promote cristae formation is unknown. Here we resolved the structure
      of the dimeric F1F0 ATP synthase complex isolated from bovine heart mitochondria
      by transmission electron microscopy. The structure of the ATP synthase dimer has
      an overall conic appearance that is consistent with the proposed role of the
      dimeric enzyme in mitochondrial cristae biogenesis. The ATP synthase dimer
      interface is formed by contacts on both the F0 and F1 domains. A cross-bridging
      protein density was resolved which connects the two F0 domains on the
      intermembrane space side of the membrane. On the matrix side of the complex, the
      two F1 moieties are connected by a protein bridge, which is attributable to the
      IF1 inhibitor protein.

PMID- 16105948
TI  - Enhancing the anticancer properties of cardiac glycosides by
      neoglycorandomization.
AB  - Glycosylated natural products are reliable platforms for the development of many
      front-line drugs, yet our understanding of the relationship between attached
      sugars and biological activity is limited by the availability of convenient
      glycosylation methods. When a universal chemical glycosylation method that
      employs reducing sugars and requires no protection or activation is used, the
      glycorandomization of digitoxin leads to analogs that display significantly
      enhanced potency and tumor specificity and suggests a divergent mechanistic
      relationship between cardiac glycoside-induced cytotoxicity and Na+/K+-ATPase
      inhibition. This report highlights the remarkable advantages of
      glycorandomization as a powerful tool in glycobiology and drug discovery.

PMID- 16105949
TI  - Geologic constraints on the macroevolutionary history of marine animals.
AB  - The causes of mass extinctions and the nature of taxonomic radiations are central
      questions in paleobiology. Several episodes of taxonomic turnover in the fossil
      record, particularly the major mass extinctions, are generally thought to
      transcend known biases in the geologic record and are widely interpreted as
      distinct macroevolutionary phenomena that require unique forcing mechanisms.
      Here, by using a previously undescribed compilation of the durations of
      sedimentary rock sequences, I compare the rates of expansion and truncation of
      preserved marine sedimentary basins to rates of origination and extinction among
      Phanerozoic marine animal genera. Many features of the highly variable record of
      taxonomic first and last occurrences in the marine animal fossil record,
      including the major mass extinctions, the frequency distribution of genus
      longevities, and short- and long-term patterns of genus diversity, can be
      predicted on the basis of the temporal continuity and quantity of preserved
      sedimentary rock. Although these results suggest that geologically mediated
      sampling biases have distorted macroevolutionary patterns in the fossil record,
      preservation biases alone cannot easily explain the extent to which the
      sedimentary record duplicates paleobiological patterns. Instead, these results
      suggest that the processes responsible for producing variability in the
      sedimentary rock record, such as plate tectonics and sea-level change, may have
      been dominant and consistent macroevolutionary forces throughout the Phanerozoic.

PMID- 16105950
TI  - Molecular basis of listeriolysin O pH dependence.
AB  - Listeriolysin O (LLO) is a cholesterol-dependent cytolysin that is an essential
      virulence factor of Listeria monocytogenes. LLO pore-forming activity is pH
      dependent; it is active at acidic pH (<6), but not at neutral pH. In contrast to
      other pH-dependent toxins, we have determined that LLO pore-forming activity is
      controlled by a rapid and irreversible denaturation of its structure at neutral
      pH at temperatures >30 degrees C. Rapid denaturation is triggered at neutral pH
      by the premature unfolding of the domain 3 transmembrane beta-hairpins;
      structures that normally form the transmembrane beta-barrel. A triad of acidic
      residues within domain 3 function as the pH sensor and initiate the denaturation
      of LLO by destabilizing the structure of domain 3. These studies provide a view
      of a molecular mechanism by which the activity of a bacterial toxin is regulated
      by pH.

PMID- 16105951
TI  - Deconstructing endogenous pain modulations.
AB  - A pathway from the midbrain periaqueductal gray (PAG) through the ventromedial
      medulla (VMM) to the dorsal horn constitutes a putative endogenous nociceptive
      modulatory system. Yet activation of neurons in both PAG and VMM changes the
      responses of dorsal horn cells to non-noxious stimuli and elicits motor and
      autonomic reactions that are not directly related to nociception. Activation of
      mu-opioid receptors in VMM and PAG also modifies processes in addition to
      nociceptive transmission. The descending projections of VMM neurons are not
      specific to nociception as VMM projects to the spinal superficial dorsal horn
      where thermoreceptors as well as nociceptors terminate. In addition, experiments
      with pseudorabies virus demonstrate multi-synaptic pathways from VMM to
      sympathetic and parasympathetic target organs. VMM neurons respond to both
      noxious and unexpected innocuous stimuli of multiple modalities, and change their
      discharge during behaviors unrelated to pain such as micturition/continence and
      sleep/wake. In conclusion, all available evidence argues against the idea that
      PAG and VMM target nociception alone. Instead these brain stem sites may effect
      homeostatic adjustments made necessary by salient situations including but not
      limited to injury.

PMID- 16105952
TI  - High level bilateral talks. Focus on "effect of low-frequency repetitive
      transcranial magnetic stimulation on interhemispheric inhibition".

PMID- 16105953
TI  - Should one hand (paw) really not know what the other is doing? Focus on "reducing
      contralateral SI activity reveals hindlimb receptive fields in the SI forelimb
      stump representation of neonatally amputated rats".

PMID- 16105954
TI  - Commissural excitation and inhibition by the superior colliculus in
      tectoreticular neurons projecting to omnipause neuron and inhibitory burst neuron
      regions.
AB  - Previous electrophysiological studies have shown that the commissural connections
      between the two superior colliculi are mainly inhibitory with fewer excitatory
      connections. However, the functional roles of the commissural connections are not
      well understood, so we sought to clarify the physiology of tectal commissural
      excitation and inhibition of tectoreticular neurons (TRNs) in the "fixation " and
      "saccade " zones of the superior colliculus (SC). By recording intracellular
      potentials, we identified TRNs by their antidromic responses to stimulation of
      the omnipause neuron (OPN) and inhibitory burst neuron (IBN) regions and analyzed
      the effects of stimulation of the contralateral SC on these TRNs in anesthetized
      cats. TRNs in the caudal SC (saccade neurons) projected to the IBN region, and
      received mono- or disynaptic inhibition from the entire rostrocaudal extent of
      the contralateral SC. In contrast, TRNs in the rostral SC projected to the OPN or
      IBN region and received monosynaptic excitation from the most rostral level of
      the contralateral SC, and mono- or disynaptic inhibition from its entire
      rostrocaudal extent. Among the rostral TRNs with commissural excitation, IBN
      projecting TRNs also projected to Forel's field H (vertical gaze center),
      suggesting that they were most likely saccade neurons related to vertical
      saccades. In contrast, TRNs projecting only to the OPN region were most likely
      fixation neurons. Most putative inhibitory neurons in the rostral SC had multiple
      axon branches throughout the rostrocaudal extent of the contralateral SC, whereas
      excitatory commissural neurons, most of which were rostral TRNs, distributed
      terminals to a discrete region in the rostral SC.

PMID- 16105955
TI  - Comparison of anterior cingulate and primary somatosensory neuronal responses to
      noxious laser-heat stimuli in conscious, behaving rats.
AB  - In this study, we investigated single-unit responses of the primary sensorimotor
      cortex (SmI) and anterior cingulate cortex (ACC) to noxious stimulation of the
      tail of the rat. The influences of morphine on these nociceptive responses were
      also compared. Multiple single-unit activities were recorded from two eight
      channel microwire arrays chronically implanted in the tail region of the SmI and
      ACC, respectively. CO2 laser-heat irradiation of the middle part of the tail at
      an intensity slightly higher than that causing a maximal tail flick response was
      used as a specific noxious stimulus. Examined individually, ACC neurons were less
      responsive than SmI neurons to laser-heat stimulus, in that only 51% of the ACC
      units (n = 125) responded compared with 88% of the SmI units (n = 74). Among
      these responsive ACC units, many had a very long latency and long-lasting
      excitatory type of response that was seldom found in the SmI. When ensemble
      activities were examined, laser heat evoked both short- (60 approximately 150 ms)
      and long-latency (151 approximately 600 ms) responses in the SmI and ACC.
      Latencies of both responses were longer in the ACC. Furthermore, a single dose of
      2.5-10 mg/kg morphine intraperitoneally suppressed only the long latency response
      in the SmI, but significantly attenuated both responses in the ACC. These effects
      of morphine were completely blocked by prior treatment with the opiate receptor
      blocker, naloxone. These results provide further evidence suggesting that the SmI
      and ACC may play different roles in processing noxious information.

PMID- 16105956
TI  - Interaction between amygdala and neocortical inputs in the perirhinal cortex.
AB  - The rhinal cortices play a critical role in high-order perceptual/mnemonic
      functions and constitute the main route for impulse traffic to and from the
      hippocampus. However, previous work has revealed that neocortical stimuli that
      activate a large proportion of perirhinal neurons are unable to discharge
      entorhinal cells. In search of mechanisms that might facilitate impulse transfer
      from the neocortex to the entorhinal cortex, we have examined changes in
      excitability produced by activation of the lateral amygdala (LA) in isoflurane
      anesthetized animals. LA stimulation activated a large proportion of peri- and
      entorhinal neurons. However, conditioning LA stimuli did not increase the ability
      of neocortical inputs to activate entorhinal cells even though such pairing
      produced marked increases in neocortically evoked field potentials and
      orthodromic firing in the perirhinal cortex. Moreover, increased neocortically
      evoked perirhinal field potentials and unit responses persisted when the
      conditioning LA shock was replaced by another neocortical stimulus at the same or
      at a different site as the testing shock. This perirhinal paired-pulse
      facilitation (PPF) was maximal with interstimulus intervals of approximately 100
      ms. Intracellular recordings of perirhinal neurons revealed that the PPF was
      generally associated with a rapid shift in the balance between inhibition and
      excitation, leading to an overall increase in perirhinal responsiveness. The
      significance of these findings for the role of the perirhinal cortex is
      discussed.

PMID- 16105957
TI  - Repetitive light stimulation inducing glycine receptor plasticity in the retinal
      neurons.
AB  - Neurotransmitter receptor plasticity is a mechanism that can regulate the
      temporal and intensity encoding of a synapse. While this has been extensively
      studied as a mechanism of learning, less is known about such processes in sensory
      systems. This study examines modulation of glycine receptor function at the first
      synapse in the retina. It was found that horizontal cells, which are postsynaptic
      to photoreceptors, have glycine receptor currents that are enhanced when internal
      calcium is elevated. This can be achieved by glutamatergic synaptic input or by
      activation of voltage-gated calcium channels. When the retina was maintained in a
      dark-adapted state, the calcium levels in horizontal cells were relatively low.
      After a series of brief light stimuli, the internal calcium concentration in
      horizontal cells was elevated, and the glycine currents were faster and greater
      in amplitude. The increase of internal calcium levels was caused by increased
      transmitter release from photoreceptors. Thus glycine receptor function is state
      dependent and can be rapidly altered by synaptic input from photoreceptors. Light
      stimulation drives glycine receptor plasticity in the retinal neural network.

PMID- 16105959
TI  - Motor unit firing statistics and the Fuglevand model.

PMID- 16105958
TI  - Experience-dependent plasticity in S1 caused by noncoincident inputs.
AB  - Prior work has shown that coincident inputs became co-represented in somatic
      sensory cortex. In this study, the hypothesis that the co-representation of
      digits required synchronous inputs was tested, and the daily development of two
      digit receptive fields was observed with cortical implants. Two adult primates
      detected temporal differences in tap pairs delivered to two adjacent digits. With
      stimulus onset asynchronies of > or = 100 ms, representations changed to include
      two-digit receptive fields across the first 4 wk of training. In addition,
      receptive fields at sites responsive to the taps enlarged more than twofold, and
      receptive fields at sites not responsive to the taps had no significant areal
      change. Further training did not increase the expression of two-digit receptive
      fields. Cortical responses to the taps were not dependent on the interval length.
      Stimuli preceding a hit, miss, false positives, and true negatives differed in
      the ongoing cortical rate from 50 to 100 ms after the stimulus but did not differ
      in the initial, principal, response to the taps. Response latencies to the
      emergent responses averaged 4.3 ms longer than old responses, which occurs if
      plasticity is cortical in origin. New response correlations developed in parallel
      with the new receptive fields. These data show co-representation can be caused by
      presentation of stimuli across a longer time window than predicted by spike
      timing-dependent plasticity and suggest that increased cortical excitability
      accompanies new task learning.

PMID- 16105961
TI  - Absence of adrenocorticotropin (ACTH) neurosecretory dysfunction but increased
      cortisol concentrations and production rates in ACTH-replete adult cancer
      survivors after cranial irradiation for nonpituitary brain tumors.
AB  - CONTEXT: For the first time, physiological cortisol secretion has been studied in
      ACTH-replete adult cancer survivors to explore any discrepancy between stimulated
      (during insulin-induced hypoglycemia) and spontaneous cortisol secretion and, in
      particular, the possible existence of ACTH neurosecretory dysfunction that might
      explain the excessive fatigue suffered by some cancer survivors. STUDY SUBJECTS:
      Cortisol profiling at 20-min intervals over 24 h during the fed state was
      undertaken in 34 patients (10 females), aged 17-53.7 yr (median, 21.5 yr), 2-29
      yr (median, 11.5 yr) after receiving conventional cranial irradiation for
      nonpituitary brain tumors or leukemia (n = 5) and in 33 age-, gender-, and body
      mass index-matched normal controls, of whom 23 patients and 17 controls were also
      profiled in the last 24 h of a 33-h fast. RESULTS: The fed profile mean cortisol
      concentration (mean +/- sem) was significantly increased (by 14%) in the patients
      compared with that in normal subjects (213 +/- 6.9 vs. 187 +/- 6.7 nmol/liter; P
      = 0.009), with all individual values above the lowest seen in normal subjects.
      Multiparameter deconvolution analysis revealed a parallel increase (by 20%) in
      cortisol secretion rates (1.8 +/- 0.09 vs. 1.5 +/- 0.08 nmol/liter.min; P = 0.03)
      due to selective augmentation of the cortisol mass released per burst with no
      changes in burst frequency (12/24 h) or half-life. No significant differences
      were observed between males and females, after short-term fasting, or between
      female patients and normal females. Thus, in the light of total group
      comparisons, male patients had even higher values than normal males, and more so
      during fasting (mean cortisol and cortisol secretion increased by 20 and 29% in
      the fed state and by 41 and 32% in the fasting state, respectively; P < 0.05).
      CONCLUSIONS: This study has demonstrated that radiation-induced ACTH
      neurosecretory dysfunction does not exist and, thus, resolved the clinical
      dilemma as to whether cortisol replacement should be considered in those patients
      with excessive fatigue and normal stimulated cortisol responses. On the contrary,
      cranial irradiation causes activation of the corticotrope-adrenal axis, and in
      the absence of ACTH deficiency, this activation is manifested by parallel
      increases in circulating cortisol levels and cortisol production rates without
      any change in cortisol half-life. The lack of cortisol increase in female
      patients may be attributed to the adverse effect of their higher body mass index
      on cortisol secretion or may reflect a genuine gender dichotomy.

PMID- 16105962
TI  - Galectin-9: a new endometrial epithelial marker for the mid- and late-secretory
      and decidual phases in humans.
AB  - CONTEXT: The galectin family has been reported to play a role in the regulation
      of cell growth, cell adhesion, apoptosis, inflammation, and immunomodulation, all
      of which are important for endometrial function, as well as implantation.
      OBJECTIVE: The objective of the study was to investigate the expression and
      regulation of galectin-9, a beta-galactoside-binding lectin in the human
      endometrium. DESIGN: Galectin-9 mRNA and protein were analyzed in dated
      endometrial biopsies throughout the menstrual cycle and in human early-pregnancy
      decidua, as well as in the different endometrial cell compartments. Regulation of
      galectin-9 by estradiol, progesterone, epidermal growth factor, and interferon
      gamma in endometrial epithelial cells in vitro was studied. RESULTS: Galectin-9
      mRNA analyzed by RNase protection assay is expressed in the human endometrium,
      specifically in the human endometrial epithelial cells but not in stromal or
      immune cells. It is expressed at very low concentrations during the proliferative
      phase and the early-secretory phase and shows a sharp and significant increase in
      the mid- and late-secretory phases, the window of implantation, as well as in the
      decidua. Accordingly, galectin-9 protein is also exclusively increased in human
      endometrial epithelial cells during the mid- and late-secretory phases and in the
      decidua, however, not in endometrial stromal cells or decidualized cells in vivo
      or in vitro. A regulation in vitro by estradiol, progesterone, epidermal growth
      factor, and interferon-gamma could not be detected. CONCLUSIONS: Based on these
      findings and on the functional studies of other galectins, we suggest galectin-9
      as a novel endometrial marker for the mid- and late-secretory and decidual
      phases.

PMID- 16105963
TI  - High frequency of skewed X-chromosome inactivation in females with autoimmune
      thyroid disease: a possible explanation for the female predisposition to thyroid
      autoimmunity.
AB  - CONTEXT: Autoimmune thyroid diseases (AITD) comprise Graves' disease (GD) and
      Hashimoto's thyroiditis (HT). They are characterized by loss of immunological
      self-tolerance and female preponderance. Theoretically, X chromosome inactivation
      (XCI) and resultant tissue chimerism could offer an explanation for the female
      predisposition to AITD. AIM: Our aim was to examine whether skewed XCI is
      associated with AITD. DESIGNS: We first conducted a classical case-control study
      of twin individuals with and without AITD, and then a case-control study of twin
      pairs discordant for AITD. PARTICIPANTS: Participants included 32 female twins
      with AITD and a control group of 96 healthy female twin individuals. METHODS: XCI
      analysis was performed by enzymatic predigestion of DNA with a methylation
      sensitive enzyme followed by PCR of the polymorphic CAG repeat of the androgen
      receptor gene. The XCI pattern was classified as skewed when 80% or more of the
      cells preferentially inactivated the same X chromosome. MAIN OUTCOME MEASURES: We
      assessed the prevalence of skewed XCI. RESULTS: The frequency of skewed XCI in
      female twins with AITD, GD, and HT was 34, 37, and 31%, respectively, which was
      higher than the prevalence in the corresponding control populations, 11% (P =
      0.003), 14% (P = 0.045), and 8% (P = 0.057), respectively. Similar results were
      found in twin pairs discordant for AITD. Overall, skewed XCI was associated with
      an increased risk of developing AITD, with an odds ratio of 9.0 (95% confidence
      interval, 1.64-49.4) (P = 0.022). CONCLUSION: These observations suggest a
      possible role of XCI in the etiology of AITD and may in part explain the female
      preponderance of AITD.

PMID- 16105964
TI  - Serum thyroid hormones in preterm infants: associations with postnatal illnesses
      and drug usage.
AB  - CONTEXT: Transient hypothyroxinemia is common in infants less than 30 wk
      gestation and is associated with neurodevelopmental deficits. Reductions in T4
      and T3 levels with TSH unchanged are the key features of severe illness using
      surrogate indices of overall severity of illness, but these do not inform the
      impact of individual disease conditions or drug use. OBJECTIVE: Our objective was
      to investigate the contribution of postnatal factors to the variations in serum
      levels of iodothyronines, thyroid-binding globulin, and TSH. DESIGN: We recruited
      a cohort of infants (23-34 wk gestation; n = 780) between January 1998 and
      September 2001. SETTING AND PATIENTS: The study involved 11 level III Scottish
      neonatal intensive care units and included cohorts of infants delivered at 23-34
      wk gestation. MAIN OUTCOME: We assessed serum levels of iodothyronines, thyroid
      binding globulin, and TSH at 7, 14, and 28 d adjusted for the potentially
      significant postnatal influences (n = 31). RESULTS: Serum levels of TSH, free T4,
      T3, and T4 are variably but significantly associated with bacteremia,
      endotracheal bacterial cultures, persistent ductus arteriosus, necrotizing
      enterocolitis, cerebral ultrasonography changes, oxygen dependence at 28 d, and
      the use of aminophylline, caffeine, dexamethasone, diamorphine, and dopamine.
      CONCLUSIONS: There are many more associations of postnatal factors with transient
      hypothyroxinemia than had previously been considered in preterm infants.
      Alternative strategies should be considered for correction of hypothyroxinemia
      rather than sole reliance on the direct therapy of hormone replacement. A more
      oblique preventative approach may be necessary through reduction in the incidence
      or severity of individual illness(es). Similarly, alternatives to those drugs
      that interfere with the hypothalamic-pituitary-thyroid axis should be evaluated
      (e.g. other inotropics instead of dopamine).

PMID- 16105965
TI  - Central fat excess in polycystic ovary syndrome: relation to low-grade
      inflammation and insulin resistance.
AB  - BACKGROUND: It is controversial whether the polycystic ovary syndrome (PCOS) per
      se increases low-grade chronic inflammation and whether this relates to central
      fat excess. In addition, the association between circulating sex hormones and
      body fat distribution in premenopausal women is debated. METHODS: Blood was drawn
      from 20 patients with PCOS and compared with 15 controls, matched for body mass
      index and age. Regional fat distribution was assessed using dual x-ray
      absorptiometry. RESULTS: Compared with controls, patients with PCOS had a higher
      trunk to extremity fat ratio (T/E fat), were more insulin resistant (higher
      homeostasis model assessment of insulin resistance and lower SHBG
      concentrations), and had higher levels of highly sensitive C-reactive protein,
      TNF-alpha, procalcitonin, and white blood cell count (all P < or = 0.04), even
      after adjusting for total body fat. However, additional adjusting for T/E fat
      eliminated or attenuated the effect of PCOS status on estimates of insulin
      resistance, on inflammatory mediators, and on white blood cell count but not on
      circulating sex hormones. Independently of each other, total body fat as well as
      T/E fat correlated with estimates of insulin resistance and most inflammatory
      mediators (P < or = 0.04). However, the correlations between T/E fat and
      circulating sex hormones (P < or = 0.02) were greatly reduced after adjustment
      for the presence of PCOS. CONCLUSION: The increase in low-grade chronic
      inflammation and in insulin resistance in women with PCOS is primarily associated
      with increased central fat excess rather than PCOS status per se. Procalcitonin
      represents a novel marker of the inflammatory activity of body fat and of PCOS.

PMID- 16105966
TI  - Cell surface targeting accounts for the difference in iodide uptake activity
      between human Na+/I- symporter and rat Na+/I- symporter.
AB  - CONTEXT: The Na+/I- symporter (NIS) has been proposed to serve as an imaging
      reporter gene to optimize vector delivery, monitor therapeutic gene expression,
      and map the tissue/organ sites of repopulated progenitor cells in vivo. In
      addition, NIS can serve as a therapeutic gene to facilitate targeted radionuclide
      therapy for various cancers. OBJECTIVE: It was reported that rat NIS (rNIS)
      confers higher radioactive iodide uptake (RAIU) activity than human NIS (hNIS).
      We aim to investigate the mechanism underlying this difference. RESULTS: We
      showed that the open reading frames (ORF) of hNIS and rNIS, although encoding for
      proteins with 83% amino acid identity, exhibit a significant difference in RAIU
      activity in transfected cells. The ORF rNIS confers four to five times higher
      RAIU activity as well as cell surface NIS accumulation than ORF hNIS despite
      similar total NIS protein levels. Multiple regions appear to play roles in the
      difference in NIS cell surface levels between ORF hNIS and ORF rNIS, indicating
      that proper folding of NIS in tertiary structure is critical for NIS cell surface
      targeting. We also showed that the kinetics of Na+ binding are different between
      ORF hNIS and ORF rNIS, and that site-directed mutation changing Ser200 to other
      uncharged amino acid significantly increased RAIU activity in ORF hNIS.
      CONCLUSIONS: NIS transgene could be optimized for cell surface trafficking and
      RAIU activity to improve its clinical applications.

PMID- 16105967
TI  - Circulating osteoprotegerin and receptor activator for nuclear factor kappaB
      ligand: clinical utility in metabolic bone disease assessment.
AB  - CONTEXT: The discovery of the receptor activator for nuclear factor kappaB (RANK)
      ligand (RANKL)/RANK signaling pathway has marked a major advance in our
      understanding of the mechanisms controlling osteoclastogenesis. RANKL, expressed
      by preosteoblasts and stromal cells, binds to RANK, expressed by cells of the
      osteoclast lineage, inducing a signaling cascade leading to the differentiation
      and fusion of osteoclast precursor cells and stimulating the activity of the
      mature osteoclast. The effects of RANKL are counteracted by osteoprotegerin
      (OPG), a soluble neutralizing decoy receptor. EVIDENCE: This paper reviews the
      literature surrounding the use of circulating OPG and soluble RANKL (sRANKL)
      measurements and assesses their potential as markers of bone disease. Original
      clinical and basic research articles and reviews were identified using a Pubmed
      search strategy (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) and cover the
      time period up until January 2005. Search terms osteoprotegerin, OPG, RANK,
      RANKL, and RANK ligand were used alone and in combination with bone,
      osteoporosis, and disease. EVIDENCE SYNTHESIS: Assays for detecting OPG and
      sRANKL in the circulation in humans have been developed, and differences in the
      circulating concentrations of OPG and sRANKL have been observed in different
      disease states. There are, however, some inconsistencies in study outcome. These
      may relate to differences in study design, methodology, and other unknown factors
      influencing the variability of these measurements. CONCLUSIONS: The clinical
      utility of serum OPG and sRANKL measurements as markers of disease activity
      requires additional investigation. In particular, rigorous testing of assays and
      identification of the sources of measurement variability are required.

PMID- 16105968
TI  - Hemostatic factors and estrogen during the menopausal transition.
AB  - BACKGROUND: It has been speculated that gender differences in cardiovascular
      disease (CVD) mortality can be attributed to the effects of estrogens on
      inflammation and hemostatic marker profiles. Therefore, we evaluated endogenous
      hormone concentrations, menopause transition stages, and adoption of exogenous
      hormone use in relation to hemostatic and inflammation marker concentrations in
      women. METHODS: Longitudinally, we studied 3302 participants from the Study of
      Women's Health Across the Nation, aged 42-52 yr at baseline and self-identified
      as African-American (28%), Caucasian (47%), Chinese (8%), Hispanic (8%), or
      Japanese (9%). Serum samples from baseline and years 2001, 2003, and 2005 were
      assayed for estradiol and FSH. Hormone concentrations were related to CVD
      markers, including fibrinogen, factor VII-c, plasminogen activator inhibitor-1
      (PAI-1), tissue plasminogen activator, and human serum C-reactive protein
      (hsCRP). RESULTS: Lower estradiol levels were associated with higher levels of
      PAI-1 and tissue plasminogen activator, but there were no significant
      relationships with fibrinogen, factor VII-c, or hsCRP. Higher FSH concentrations
      were associated with higher PAI-1 and factor VII levels, but lower fibrinogen and
      hsCRP levels. Transitions from premenopause and early perimenopause to
      postmenopause were not associated with significant differences in levels of
      hemostatic factors. The hsCRP concentrations were approximately 25% higher, and
      the PAI-1 concentrations approximately 20% lower among women who initiated
      hormone therapy, compared with nonusers. SUMMARY: Endogenous estrogens may reduce
      CVD risk via modulation of fibrinolytic factors, but not coagulation or
      inflammatory markers. Notably, conclusions derived from studies of exogenous
      hormones and CVD risk may not parallel or explain the effects of endogenous
      hormones or perimenopausal hormone changes on CVD risk.

PMID- 16105969
TI  - Immunohistochemical localization of CCK1 cholecystokinin receptors in normal and
      neoplastic human tissues.
AB  - BACKGROUND: The biological effects of cholecystokinin (CCK) are mediated by two
      distinct G protein-coupled receptors, CCK1 and CCK2. Although it is well
      established that CCK receptors are widely distributed throughout the normal
      gastrointestinal tract, little is known about their cellular and subcellular
      localization in human normal and neoplastic tissues. METHODS: We developed and
      characterized a novel antipeptide antibody to the carboxyl-terminal region of the
      human CCK1 receptor. Specificity of the antiserum was demonstrated by 1)
      detection of a broad band migrating at a relative molecular mass of 85,000-95,000
      in Western blots of membranes from CCK1-expressing tumors and CCK1-transfected
      cells, 2) cell surface staining of CCK1-transfected cells, 3) translocation of
      CCK1 receptor immunostaining after agonist exposure, and 4) abolition of tissue
      immunostaining by preadsorption of the antibody with its immunizing peptide. The
      distribution of CCK1 receptors was investigated in 74 human tumors and their
      tissues of origin. RESULTS: The presence of CCK1 receptors was rarely detected in
      human tumors except for carcinoids, insulinomas, pituitary adenomas, and
      meningiomas. CCK1 receptors were clearly located at the plasma membrane and
      uniformly present on nearly all tumor cells. In the gastrointestinal tract, CCK1
      receptor immunoreactivity was highly abundant in chief cells of the gastric
      mucosa, in myenteric ganglion cells, and in myenteric nerve fibers. CONCLUSION:
      This is the first localization of CCK1 receptors in human formalin-fixed,
      paraffin-embedded tissues at the cellular level. The overexpression of CCK1
      receptors in a subset of human neuroendocrine tumors may provide a molecular
      basis for efficient targeting of these tumors with radiolabeled CCK analogs.

PMID- 16105970
TI  - Contractile activity of human decidual stromal cells. II. Effect of interleukin
      10.
AB  - CONTEXT: Human decidual stromal cells (DSC) are myofibroblast-like cells that
      express alpha-smooth muscle (alpha-SM) actin, a protein associated with cell
      contractility. Several lines of experimental evidence in humans and mice show
      that antiinflammatory cytokines favor normal pregnancy, whereas Th1 and
      inflammatory cytokines play a role in abortion. We previously demonstrated that
      IL-2, a Th1 cytokine, increased the contractility of human DSC. OBJECTIVE: We
      studied the effect of the antiinflammatory cytokines IL-10 and IL-4 on the
      contractility of DSC from first-trimester pregnancy. SETTING AND PATIENTS: We
      studied 10 healthy women who underwent elective vaginal termination of first
      trimester pregnancy at Clinica El Sur, Malaga, and Clinica Ginegranada, Granada.
      MAIN OUTCOME MEASURE(S): After isolation of DSC, cell contractility was measured
      with the collagen gel contraction assay. alpha-SM actin was detected with Western
      blotting and immunofluorescence. RESULTS: We found that IL-10, but not IL-4,
      increased the volume of the collagen gel matrixes in which the cytokine-treated
      DSC were cultured, showing that IL-10 decreased DSC contractility. By Western
      blotting we demonstrated that this effect was not related to an alteration in the
      synthesis of alpha-SM actin. Nevertheless, we observed by immunofluorescence
      microscopy that DSC treated with IL-10 exhibited stress fibers with a lower
      content of alpha-SM actin than untreated control DSC. CONCLUSIONS: IL-10 relaxes
      DSC by reducing the incorporation of alpha-SM actin into their stress fibers.
      This relaxing activity may be of relevance for the maintenance of pregnancy.

PMID- 16105971
TI  - Duodenal somatostatinoma associated with diabetic ketoacidosis presumably caused
      by somatostatin-28 hypersecretion.
AB  - CONTEXT: Extrapancreatic somatostatinoma is very rare and clinically
      distinguished from its pancreatic counterpart because somatostatinoma syndrome
      with mild diabetes is rare in extrapancreatic somatostatinoma because of poor
      secretion of somatostatin. Moreover, because somatostatin inhibits the secretion
      of insulin and glucagon simultaneously, true diabetic ketoacidosis (DKA) seldom
      ensues. PATIENT: A 23-yr-old woman presented with DKA and an abdominal mass. A
      computed tomography scan showed a huge, encapsulated mass in a duodenal submucous
      portion. A high circulating level of somatostatin was detected (67.2 pmol/liter;
      reference range, 0.6-7.3 pmol/liter). INTERVENTION: The tumor mass was
      successfully removed with Whipple's procedure, and the patient gradually
      recovered both clinically and biochemically. RESULTS: Immunohistochemical
      staining of the tumor tissue exhibited diffusely positive for somatostatin and
      somatostatin-28 but negative for insulin, glucagon, calcitonin, serotonin, and S
      100. CONCLUSION: As far as we know, this is the first case report of
      gastrointestinal somatostatinoma associated with DKA.

PMID- 16105972
TI  - L-selectin and beta7 integrin on donor CD4 T cells are required for the early
      migration to host mesenteric lymph nodes and acute colitis of graft-versus-host
      disease.
AB  - The homing receptors L-selectin and alpha4beta7 integrin facilitate entry of T
      cells into the gut-associated organized lymphoid tissues such as the mesenteric
      lymph nodes and Peyer patches. We studied the impact of inactivation of genes
      encoding these receptors on the ability of purified donor CD4+ T cells to induce
      acute lethal graft-versus-host disease (GVHD) associated with severe colitis in
      irradiated major histocompatibility complex (MHC)-mismatched mice. Whereas lack
      of expression of a single receptor had no significant impact on the severity of
      colitis and GVHD, the lack of expression of both receptors markedly ameliorated
      colitis and early deaths observed with wild-type (WT) T cells. The changes in
      colitis and GVHD were reflected in a marked reduction in the early accumulation
      of donor T cells in the mesenteric lymph nodes and subsequently in the colon. The
      purified WT donor CD4+ T cells did not accumulate early in the Peyer patches and
      failed to induce acute injury to the small intestine. In conclusion, the
      combination of CD62L and beta7 integrin is required to induce acute colitis and
      facilitate entry of CD4+ donor T cells in the mesenteric nodes associated with
      lethal GVHD in allogeneic hosts.

PMID- 16105973
TI  - Shear stress affects the intracellular distribution of eNOS: direct demonstration
      by a novel in vivo technique.
AB  - The focal location of atherosclerosis in the vascular tree is correlated with
      local variations in shear stress. We developed a method to induce defined
      variations in shear stress in a straight vessel segment of a mouse. To this end,
      a cylinder with a tapered lumen was placed around the carotid artery, inducing a
      high shear stress field. Concomitantly, regions of low shear stress and
      oscillatory shear stress were created upstream and down-stream of the device,
      respectively. This device was used in mice transgenic for an eNOS3GFP fusion
      gene. We observed a strong induction of endothelial nitric oxide synthase-green
      fluorescent protein (eNOS-GFP) mRNA expression in the high shear stress region
      compared with the other regions (P < .05). Quantification of eNOS-GFP
      fluorescence or of immunoreactivity to the Golgi complex or to platelet
      endothelial cell adhesion molecule 1 (PECAM-1) showed an increase in the high
      shear stress region (P < .05) compared with nontreated carotid arteries.
      Colocalization of eNOS-GFP with either the Golgi complex or PECAM-1 also
      responded to alterations of shear stress. In conclusion, we showed a direct
      response of mRNA and protein expression in vivo to induced variations of shear
      stress. This model provides the opportunity to study the relationship between
      shear stress alterations, gene expression, and atherosclerosis.

PMID- 16105974
TI  - NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a
      novel agent for imatinib-resistant leukemia.
AB  - Although the Abelson (Abl) tyrosine kinase inhibitor imatinib mesylate has
      improved the treatment of breakpoint cluster region-Abl (Bcr-Abl)-positive
      leukemia, resistance is often reported in patients with advanced-stage disease.
      Although several Src inhibitors are more effective than imatinib and
      simultaneously inhibit Lyn, whose overexpression is associated with imatinib
      resistance, these inhibitors are less specific than imatinib. We have identified
      a specific dual Abl-Lyn inhibitor, NS-187 (elsewhere described as CNS-9), which
      is 25 to 55 times more potent than imatinib in vitro. NS-187 is also at least 10
      times as effective as imatinib in suppressing the growth of Bcr-Abl-bearing
      tumors and markedly extends the survival of mice bearing such tumors. The
      inhibitory effect of NS-187 extends to 12 of 13 Bcr-Abl proteins with mutations
      in their kinase domain but not to T315I. NS-187 also inhibits Lyn without
      affecting the phosphorylation of Src, Blk, or Yes. These results suggest that NS
      187 may be a potentially valuable novel agent to combat imatinib-resistant
      Philadelphia-positive (Ph+) leukemia.

PMID- 16105975
TI  - High-dose therapy intensification compared with continued standard chemotherapy
      in multiple myeloma patients responding to the initial chemotherapy: long-term
      results from a prospective randomized trial from the Spanish cooperative group
      PETHEMA.
AB  - The aim of the present randomized trial was to compare high-dose therapy (HDT)
      with continued conventional chemotherapy in patients with multiple myeloma (MM)
      who responded to the initial treatment. From May 1994 to October 1999, 216
      patients (122 men/94 women; stage II or III; Eastern Cooperative Oncology Group
      [ECOG] score less than 3) entered the study. Initial chemotherapy consisted of 4
      cycles of alternating vincristine, BCNU, melphalan, cyclophosphamide,
      prednisone/vincristine, BCNU, Adriamycin, dexamethasone (VBMCP/VBAD). Responding
      patients were randomly assigned to receive 8 additional cycles of VBMCP/VBAD,
      intensification with melphalan 200 mg/m2, or melphalan 140 mg/m2 plus 12 Gy
      fractionated total body irradiation (TBI). One-hundred sixty-four patients were
      randomly assigned, 83 to continued chemotherapy and 81 to HDT. The complete
      remission (CR) rate was significantly higher with HDT (30% vs 11%; P = .002).
      However, progression-free survival (PFS) was not significantly different between
      HDT and conventional therapy (median, 42 vs 33 months; P = not significant [NS]),
      and overall survival (OS) was similar in both groups (median, 61 vs 66 months).
      Finally, survival after relapse was identical in the 2 arms (15.9 vs 16.4
      months). In conclusion, these results show that HDT intensification, when given
      to myeloma patients who have responded to the initial chemotherapy, significantly
      increases the CR rate but has no significant impact on PFS or OS.

PMID- 16105976
TI  - PPAR-gamma agonists inhibit toll-like receptor-mediated activation of dendritic
      cells via the MAP kinase and NF-kappaB pathways.
AB  - Dendritic cells (DCs) play an important role in initiating and maintaining
      primary immune responses. However, mechanisms involved in the resolution of these
      responses are elusive. We analyzed the effects of 15d-PGJ2 and the synthetic
      peroxisome proliferator-activated receptor (PPAR)-gamma ligand troglitazone (TGZ)
      on the immunogenicity of human monocyte-derived DCs upon stimulation with toll
      like receptor (TLR) ligands. Activation of PPAR-gamma resulted in a reduced
      stimulation of DCs via the TLR ligands 2, 3, 4, and 7, characterized by down
      regulation of costimulatory and adhesion molecules and reduced secretion of
      cytokines and chemokines involved in T-lymphocyte activation and recruitment. MCP
      1 (monocyte chemotactic protein-1) production was increased due to PPAR-gamma
      activation. Furthermore, TGZ-treated DCs showed a significantly reduced capacity
      to stimulate T-cell proliferation, emphasizing the inhibitory effect of PPAR
      gamma activation on TLR-induced DC maturation. Western blot analyses revealed
      that these inhibitory effects on TLR-induced DC activation were mediated via
      inhibition of the NF-kappaB and mitogen-activated protein (MAP) kinase pathways
      while not affecting the PI3 kinase/Akt signaling. Our data demonstrate that
      inhibition of the MAP kinase and NF-kappaB pathways is critically involved in the
      regulation of TLR and PPAR-gamma-mediated signaling in DCs.

PMID- 16105977
TI  - Durable engraftment of AMD3100-mobilized autologous and allogeneic peripheral
      blood mononuclear cells in a canine transplantation model.
AB  - Peripheral-blood mononuclear cells (PBMCs) mobilized with AMD3100, a CXCR4
      antagonist, combined with granulocyte colony-stimulating factor (G-CSF) have
      reconstituted autologous hematopoiesis in cancer patients following myeloablative
      conditioning. The engraftment potential of PBMCs mobilized with AMD3100 alone,
      however, has remained unproven. We therefore studied AMD3100-mobilized PBMCs in a
      canine model. Four dogs received 920 cGy total body irradiation (TBI) before
      infusion of autologous AMD3100-mobilized PBMCs (median CD34 cell count, 3.9 x
      10(6)/kg). Neutrophil (> 0.5 x 10(9)/L [500/microL]) and platelet (> 20 x 10(9)/L
      [> 20 000/microL]) recoveries occurred at medians of 9 (range, 7-10) days and 25
      (range, 23-38) days, respectively, after TBI, and all dogs had normal marrow
      function at 1 year after transplantation. To evaluate the long-term engraftment
      potential of AMD3100-mobilized PBMCs, 5 dogs were given 920 cGy TBI followed by
      infusion of AMD3100-mobilized PBMCs (median CD34 cell dose, 4.7 x 10(6)/kg) from
      their dog leukocyte antigen (DLA)-identical littermates. Neutrophil and platelet
      recoveries occurred at medians of 8 (range, 8-10) days and 26 (range, 26-37)
      days, respectively, after TBI. With a median follow-up of 53 (range, 33-61)
      weeks, recipients' marrow function was normal, and blood-donor chimerism levels
      were 97% to 100%. In summary, both autologous and allogeneic AMD3100-mobilized
      PBMCs led to prompt and durable engraftment in dogs after 920 cGy TBI.

PMID- 16105978
TI  - Relationship between FLT3 mutation status, biologic characteristics, and response
      to targeted therapy in acute promyelocytic leukemia.
AB  - The prognostic significance of FLT3 mutations in acute promyelocytic leukemia
      (APL) is not firmly established and is of particular interest given the
      opportunities for targeted therapies using FLT3 inhibitors. We studied 203
      patients with PML-RARA-positive APL; 43% of the patients had an FLT3 mutation (65
      internal tandem duplications [ITDs], 19 D835/I836, 4 ITD+D835/I836). Both
      mutations were associated with higher white blood cell (WBC) count at
      presentation; 75% of the patients with WBC counts of 10 x 10(9)/L or greater had
      mutant FLT3. FLT3/ITDs were correlated with M3v subtype (P < .001), bcr3 PML
      breakpoint (P < .001), and expression of reciprocal RARA-PML transcripts (P =
      .01). Microarray analysis revealed differences in expression profiles among
      patients with FLT3/ITD, D835/I836, and wild-type FLT3. Patients with mutant FLT3
      had a higher rate of induction death (19% vs 9%; P = .04, but no significant
      difference in relapse risk (28% vs 23%; P = .5) or overall survival (59% vs 67%;
      P = .2) at 5 years. In in vitro differentiation assays using primary APL blasts
      (n = 6), the FLT3 inhibitor CEP-701 had a greater effect on cell
      survival/proliferation in FLT3/ITD+ cells, but this inhibition was reduced in the
      presence of ATRA. Furthermore, in the presence of CEP-701, ATRA-induced
      differentiation was reduced in FLT3/ITD+ cells. These data carry implications for
      the use of FLT3 inhibitors as frontline therapy for APL.

PMID- 16105979
TI  - Conditional MN1-TEL knock-in mice develop acute myeloid leukemia in conjunction
      with overexpression of HOXA9.
AB  - The chromosomal translocation t(12; 22)(p13;q11) in human myeloid leukemia
      generates an MN1-TEL (meningioma 1-translocation-ETS-leukemia) fusion
      oncoprotein. This protein consists of N-terminal MN1 sequences, a transcriptional
      coactivator fused to C-terminal TEL sequences, an ETS (E26 transformation
      specific) transcription factor. Enforced expression of MN1-TEL in multipotent
      hematopoietic progenitors in knock-in mice perturbed growth and differentiation
      of myeloid as well as lymphoid cells. Depending on obligatory secondary
      mutations, these mice developed T-cell lympholeukemia. Here we addressed the role
      of MN1-TEL in myeloid leukemogenesis using the same mouse model. Expression of
      MN1-TEL enhanced the growth of myeloid progenitors in an interleukin 3/stem cell
      factor (IL-3/SCF)-dependent manner in vitro whereas 10% of MN1-TEL-expressing
      mice developed altered myelopoiesis with severe anemia after long latency.
      Coexpression of MN1-TEL and IL-3, but not SCF, rapidly caused a fatal
      myeloproliferative disease rather than acute myeloid leukemia (AML). Because MN1
      TEL+ AML patient cells overexpress HOXA9 (homeobox A9), we tested the effect of
      coexpression of MN1-TEL and HOXA9 in mice and found that 90% of MN1-TEL+/HOXA9+
      mice developed AML much more rapidly than control HOXA9+ mice. Thus, the
      leukemogenic effect of MN1-TEL in our knock-in mice is pleiotropic, and the type
      of secondary mutation determines disease outcome.

PMID- 16105980
TI  - The extracellular matrix protein mindin serves as an integrin ligand and is
      critical for inflammatory cell recruitment.
AB  - Leukocyte recruitment to inflammation sites depends on interactions between
      integrins and extracellular matrix (ECM). In this report we show that mice
      lacking the ECM protein mindin exhibit severely impaired recruitment of
      neutrophils and macrophages in 4 different inflammation models. Furthermore,
      neutrophils directly bind to immobilized mindin, and mindin matrix mediates
      neutrophil migration in vitro. The adhesion of neutrophils to mindin is blocked
      by anti-integrin alpha4, anti-integrin alpha(M), and anti-integrin beta2
      antibodies. We also show that HEK-293 cells transfected with cDNA encoding these
      integrins exhibit enhanced binding to immobilized mindin matrix and the increased
      binding can be blocked by anti-integrin antibodies. Our results suggest that
      mindin serves as a novel ligand for integrins and mindin-integrin interactions
      are critical for inflammatory cell recruitment in vivo.

PMID- 16105981
TI  - Induction therapy for adults with acute lymphoblastic leukemia: results of more
      than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993.
AB  - The international acute lymphoblastic leukemia (ALL) study was designed to
      prospectively define the optimal therapy for adults 60 years of age or younger
      with newly diagnosed ALL. All patients received identical induction therapy, and
      91% achieved complete remission (CR). Patients 50 years of age or younger with a
      compatible sibling were assigned to undergo allogeneic transplantation; the
      others were randomly assigned to autologous transplantation or to
      consolidation/maintenance therapy for 2.5 years. Patients who did not achieve CR
      after induction had an overall survival rate of 5% compared with 45% for patients
      who achieved CR. Factors at diagnosis predictive of overall survival and disease
      free survival were age (P = .001), white blood cell count less than 30 x 10(9)/L
      for B lineage or less than 100 x 10(9)/L for T lineage (P = .001) and
      immunophenotype, T lineage versus B lineage (P = .001). The data demonstrate that
      achieving CR with induction therapy is indispensable for long-term survival in
      adult patients with ALL. Furthermore, with a response rate greater than 90%, the
      induction regimen was highly efficacious as remission-inducing therapy. This
      large database has validated several previously identified independent prognostic
      factors in ALL, such as age, white blood cell count at presentation,
      cytogenetics, and immunophenotype. However, the achievement of CR within 4 weeks
      does not appear to be an independent prognostic factor.

PMID- 16105982
TI  - NF-kappaB and FLIP in arsenic trioxide (ATO)-induced apoptosis in myelodysplastic
      syndromes (MDSs).
AB  - Tumor necrosis factor (TNF)-alpha, a potent stimulus of nuclear factor-kappaB (NF
      kappaB), is up-regulated in myelodysplastic syndrome (MDS). Here, we show that
      bone marrow mononuclear cells (BMMCs) and purified CD34+ cells from patients with
      low-grade/early-stage MDS (refractory anemia/refractory anemia with ring
      sideroblasts [RA/RARS]) have low levels of NF-kappaB activity in nuclear extracts
      comparable with normal marrow, while patients with RA with excess blasts (RAEB)
      show significantly increased levels of activity (P = .008). Exogenous TNF-alpha
      enhanced NF-kappaB nuclear translocation in MDS BMMCs above baseline levels.
      Treatment with arsenic trioxide (ATO; 2-200 microM) inhibited NF-kappaB activity
      in normal marrow, primary MDS, and ML1 cells, even in the presence of exogenous
      TNF-alpha (20 ng/mL), and down-regulated NF-kappaB-dependent antiapoptotic
      proteins, B-cell leukemia XL (Bcl-XL), Bcl-2, X-linked inhibitor of apoptosis
      (XIAP), and Fas-associated death domain (FADD)-like interleukin-1beta-converting
      enzyme (FLICE) inhibitory protein (FLIP), leading to apoptosis. However,
      overexpression of FLIP resulted in increased NF-kappaB activity and rendered ML1
      cells resistant to ATO-induced apoptosis. These data are consistent with the
      observed up-regulation of FLIP and resistance to apoptosis with advanced MDS,
      where ATO as a single agent may show only limited efficacy. However, the data
      also suggest that combinations of ATO with agents that interfere with other
      pathways, such as FLIP autoamplification via NF-kappaB, may have considerable
      therapeutic activity.

PMID- 16105983
TI  - Role of FcRgamma and factor XIIIA in coated platelet formation.
AB  - Platelet activation in response to dual stimulation with collagen and thrombin
      results in the formation of a subpopulation of activated platelets known as
      coated platelets. Coated platelets are characterized by high surface levels of
      alpha-granule proteins and phosphatidylserine, which support the assembly of
      procoagulant protein complexes. Using murine models, we tested the hypothesis
      that the collagen receptor-associated molecule FcRgamma and the transglutaminase
      factor XIIIA are required for the formation of coated platelets. Following dual
      stimulation with the collagen receptor agonist convulxin and thrombin, 68% of
      platelets from C57BL/6 mice acquired the coated platelet phenotype, defined by
      high surface levels of fibrinogen and von Willebrand factor and decreased binding
      of the alphaIIbbeta3 activation-dependent antibody PE-JON/A. In FcRgamma-/- mice,
      only 10% of platelets became "coated" after dual stimulation with convulxin plus
      thrombin (P < .05 vs C57BL/6 platelets). Decreased coated platelet formation in
      FcRgamma-/- platelets was accompanied by decreased annexin V binding (P < .01)
      and decreased platelet procoagulant activity (P < .05). Platelets from FXIIIA-/-
      mice did not differ from control platelets in coated platelet formation or
      annexin V binding. We conclude that FcRgamma, but not factor XIIIA, is essential
      for formation of highly procoagulant coated platelets following dual stimulation
      with collagen and thrombin.

PMID- 16105984
TI  - p130Cas mediates the transforming properties of the anaplastic lymphoma kinase.
AB  - Translocations of the anaplastic lymphoma kinase (ALK) gene have been described
      in anaplastic large-cell lymphomas (ALCLs) and in stromal tumors. The most
      frequent translocation, t(2;5), generates the fusion protein nucleophosmin (NPM)
      ALK with intrinsic tyrosine kinase activity. Along with transformation, NPM-ALK
      induces morphologic changes in fibroblasts and lymphoid cells, suggesting a
      direct role of ALK in cell shaping. In this study, we used a mass-spectrometry
      based proteomic approach to search for proteins involved in cytoskeleton
      remodeling and identified p130Cas (p130 Crk-associated substrate) as a novel
      interactor of NPM-ALK. In 293 cells and in fibroblasts as well as in human ALK
      positive lymphoma cell lines, NPM-ALK was able to bind p130Cas and to induce its
      phosphorylation. Both of the effects were dependent on ALK kinase activity and on
      the adaptor protein growth factor receptor-bound protein 2 (Grb2), since no
      binding or phosphorylation was found with the kinase-dead mutant NPM-ALK(K210R)
      or in the presence of a Grb2 dominant-negative protein. Phosphorylation of
      p130Cas by NPM-ALK was partially independent from Src (tyrosine kinase pp60c-src)
      kinase activity, as it was still detectable in Syf-/- cells. Finally, p130Cas-/-
      (also known as Bcar1-/-) fibroblasts expressing NPM-ALK showed impaired actin
      filament depolymerization and were no longer transformed compared with wild-type
      cells, indicating an essential role of p130Cas activation in ALK-mediated
      transformation.

PMID- 16105985
TI  - Timely triggering of homeostatic mechanisms involved in the regulation of T-cell
      levels in SIVsm-infected sooty mangabeys.
AB  - Sooty mangabeys, the natural host of simian immunodeficiency virus (SIVsm),
      generally avoid progressive depletion of CD4+ T cells and opportunistic
      infections associated with infection of humans (HIV) and macaques (SIVmac). The
      means by which the SIVsm-infected mangabeys maintain CD4+ T-cell levels despite
      high rates of viral replication is unknown. One cytokine that has a key role in
      the regulation of T-cell levels is interleukin-7 (IL-7). Here, the longitudinal
      assessment of 6 SIVsm-infected mangabeys identified an early increase in plasma
      IL-7 levels at weeks 1 to 5 after infection. This IL-7 increase correlated with
      an early decline in CD4+ T-cell levels (decline of 492-1171 cells/microL)
      accompanying acute viremia. Elevated IL-7 levels were followed by increased T
      cell proliferation (Ki67) and maintenance of lower but stable (more than 500
      cells/microL) CD4+ T-cell levels in each mangabey through 37 weeks of infection.
      These data contrast with our earlier studies in SIVmac-infected macaques, in
      which the IL-7 increase was delayed until 20 to 40 weeks after infection, just
      before the onset of simian AIDS. Taken together, these data suggest that timely
      triggering of IL-7 is important for stabilizing healthy T-cell levels in
      mangabeys and that timely administration of exogenous IL-7 may show benefit
      during pathogenic SIVmac and HIV infection.

PMID- 16105986
TI  - Gametes alter the oviductal secretory proteome.
AB  - The mammalian oviduct provides an optimal environment for the maturation of
      gametes, fertilization, and early embryonic development. Secretory cells lining
      the lumen of the mammalian oviduct synthesize and secrete proteins that have been
      shown to interact with and influence the activities of gametes and embryos. We
      hypothesized that the presence of gametes in the oviduct alters the oviductal
      secretory proteomic profile. We used a combination of two-dimensional gel
      electrophoresis and liquid chromatography-tandem mass spectrometry to identify
      oviductal protein secretions that were altered in response to the presence of
      gametes in the oviduct. The oviductal response to spermatozoa was different from
      its response to oocytes as verified by Western blotting. The presence of
      spermatozoa or oocytes in the oviduct altered the secretion of specific proteins.
      Most of these proteins are known to have an influence on gamete maturation,
      viability, and function, and there is evidence to suggest these proteins may
      prepare the oviductal environment for arrival of the zygote. Our findings suggest
      the presence of a gamete recognition system within the oviduct capable of
      distinguishing between spermatozoa and oocytes.

PMID- 16105987
TI  - Analysis of human multidrug resistance protein 1 (ABCC1) by matrix-assisted laser
      desorption ionization/time of flight mass spectrometry: toward identification of
      leukotriene C4 binding sites.
AB  - Multidrug resistance in tumor cells may be caused by reduced drug accumulation
      resulting from expression of one or more proteins belonging to the ATP-binding
      cassette (ABC) transporter superfamily. In addition to their drug efflux
      properties, certain ABC proteins such as multidrug resistance protein 1 (MRP1)
      (ABCC1) mediate the ATP-dependent transport of a broad array of organic anions.
      The intrinsically photoreactive glutathione-conjugated cysteinyl leukotriene C4
      (LTC4) is a high-affinity physiological substrate of MRP1 and is widely regarded
      as a model compound for evaluating the substrate binding and transport properties
      of wild-type and mutant forms of the transporter. In the present study, we have
      optimized high-level expression of recombinant human MRP1 in Pichia pastoris and
      developed a two-step purification scheme that results in purification of the
      transporter to >90% homogeneity. Peptide mapping by matrix-assisted laser
      desorption ionization/time of flight mass spectrometry of the peptides generated
      by in-gel protease digestions of purified underglycosylated MRP1 identified 96.7%
      of the MRP1 sequence with >98% coverage of its 17 transmembrane helices.
      Subsequent comparisons with mass spectra of MRP1 photolabeled with LTC4
      identified six candidate LTC4-modified peptide fragments that are consistent with
      the conclusion that the intracellular juxtamembrane positions of transmembrane
      helices 6, 7, 10, 17, and a COOH-proximal portion of the cytoplasmic loop that
      links the first and second membrane spanning domains are part of the LTC4 binding
      site of the transporter. Our studies confirm the usefulness of mass spectrometry
      for analysis of mammalian polytopic membrane proteins and for identification of
      substrate binding sites of human MRP1.

PMID- 16105988
TI  - Scavenger receptors on sinusoidal liver endothelial cells are involved in the
      uptake of aldehyde-modified proteins.
AB  - Scavenger receptors on sinusoidal liver endothelial cells (SECs) eliminate
      potentially harmful modified proteins circulating through the liver. It was shown
      recently that aldehyde-modified proteins bind to scavenger receptors and are
      associated with the development/progression of alcoholic liver diseases. For
      these studies, rat livers were perfused in situ with 125I-formaldehyde-bovine
      serum albumin (f-Alb) or 125I-malondialdehyde-acetaldehyde-bovine serum albumin
      (MAA-Alb) in the presence of known scavenger receptor ligands as inhibitors.
      Reverse transcription-polymerase chain reaction (RT-PCR) analysis and scavenger
      receptor Type A (SRA) knock-out mice were used to assess the role of these
      receptors in mediating immune responses. The degradation of 125I-f-Alb or 125I
      MAA-Alb in whole livers and isolated SECs can be inhibited by known scavenger
      receptor ligands, including f-Alb, maleylated bovine albumin, and fucoidan. 125I
      f-Alb could not be completely inhibited by MAA-Alb. In contrast, 125I-MAA-Alb was
      only partially inhibited with advanced glycosylated endproduct albumin. RT-PCR
      data show the presence of a number of scavenger receptors on SECs that may be
      responsible for the binding of MAA-modified proteins. SRA seems to be one of
      these receptors involved in the effects mediated by MAA-modified proteins. In a
      study using SRA knockout mice, it was shown that a decreased antibody response to
      MAA-Alb resulted. By RT-PCR, CD36, LOX-1, and SR-AI are the scavenger receptors
      most likely involved in the degradation of MAA-Alb.

PMID- 16105989
TI  - Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization.
AB  - BACKGROUND: Sirolimus-eluting stents and paclitaxel-eluting stents, as compared
      with bare-metal stents, reduce the risk of restenosis. It is unclear whether
      there are differences in safety and efficacy between the two types of drug
      eluting stents. METHODS: We conducted a randomized, controlled, single-blind
      trial comparing sirolimus-eluting stents with paclitaxel-eluting stents in 1012
      patients undergoing percutaneous coronary intervention. The primary end point was
      a composite of major adverse cardiac events (death from cardiac causes,
      myocardial infarction, and ischemia-driven revascularization of the target
      lesion) by nine months. Follow-up angiography was completed in 540 of 1012
      patients (53.4 percent). RESULTS: The two groups had similar baseline clinical
      and angiographic characteristics. The rate of major adverse cardiac events at
      nine months was 6.2 percent in the sirolimus-stent group and 10.8 percent in the
      paclitaxel-stent group (hazard ratio, 0.56; 95 percent confidence interval, 0.36
      to 0.86; P=0.009). The difference was driven by a lower rate of target-lesion
      revascularization in the sirolimus-stent group than in the paclitaxel-stent group
      (4.8 percent vs. 8.3 percent; hazard ratio, 0.56; 95 percent confidence interval,
      0.34 to 0.93; P=0.03). Rates of death from cardiac causes were 0.6 percent in the
      sirolimus-stent group and 1.6 percent in the paclitaxel-stent group (P=0.15); the
      rates of myocardial infarction were 2.8 percent and 3.5 percent, respectively
      (P=0.49); and the rates of angiographic restenosis were 6.6 percent and 11.7
      percent, respectively (P=0.02). CONCLUSIONS: As compared with paclitaxel-eluting
      stents, the use of sirolimus-eluting stents results in fewer major adverse
      cardiac events, primarily by decreasing the rates of clinical and angiographic
      restenosis.

PMID- 16105990
TI  - Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic
      patients.
AB  - BACKGROUND: Drug-eluting stents are highly effective in reducing the rate of in
      stent restenosis. It is not known whether there are differences in the
      effectiveness of currently approved drug-eluting stents in the high-risk subgroup
      of patients with diabetes mellitus. METHODS: We enrolled 250 patients with
      diabetes and coronary artery disease: 125 were randomly assigned to receive
      paclitaxel-eluting stents, and 125 to receive sirolimus-eluting stents. The
      primary end point was in-segment late luminal loss. Secondary end points were
      angiographic restenosis (defined as in-segment stenosis of at least 50 percent at
      follow-up angiography) and the need for revascularization of the target lesion
      during a nine-month follow-up period. The study was designed to show
      noninferiority of the paclitaxel stent as compared with the sirolimus stent,
      defined as a difference in the extent of in-segment late luminal loss of no more
      than 0.16 mm. RESULTS: The extent of in-segment late luminal loss was 0.24 mm (95
      percent confidence interval, 0.09 to 0.39) greater in the paclitaxel-stent group
      than in the sirolimus-stent group (P=0.002). In-segment restenosis was identified
      on follow-up angiography in 16.5 percent of the patients in the paclitaxel-stent
      group and 6.9 percent of the patients in the sirolimus-stent group (P=0.03).
      Target-lesion revascularization was performed in 12.0 percent of the patients in
      the paclitaxel-stent group and 6.4 percent of the patients in the sirolimus-stent
      group (P=0.13). CONCLUSIONS: In patients with diabetes mellitus and coronary
      artery disease, use of the sirolimus-eluting stent is associated with a decrease
      in the extent of late luminal loss, as compared with use of the paclitaxel
      eluting stent, suggesting a reduced risk of restenosis.

PMID- 16105991
TI  - Healing Achilles--sirolimus versus paclitaxel.

PMID- 16105992
TI  - The cover. La Manne-Porte, Etretat.

PMID- 16105993
TI  - Neuroscience becomes image conscious as brain scans raise ethical issues.

PMID- 16105994
TI  - Scientists confront cloning challenges.

PMID- 16105995
TI  - Office-based treatment for opioid addiction achieving goals.

PMID- 16106000
TI  - Chronic kidney disease and cardiovascular risk.

PMID- 16106001
TI  - Folate and vitamin B12 for hip fracture prevention after stroke.

PMID- 16106002
TI  - Controlling for patient case mix at the end of life: issues in identifying cause
      of death.

PMID- 16106003
TI  - Family physicians and options for childbirth care.

PMID- 16106004
TI  - Impact of varicella vaccination on health care utilization.
AB  - CONTEXT: Since varicella vaccine was first recommended for routine immunization
      in the United States in 1995, the incidence of disease has dropped substantially.
      However, national surveillance data are incomplete, and comprehensive data
      regarding outpatient as well as hospital utilization have not been reported.
      OBJECTIVE: To examine the impact of the varicella vaccination program on medical
      visits and associated expenditures. DESIGN, SETTING, AND PATIENTS: Retrospective
      population-based study examining the trends in varicella health care utilization,
      based on data from the MarketScan databases, which include enrollees (children
      and adults) of more than 100 health insurance plans of approximately 40 large US
      employers, from 1994 to 2002. MAIN OUTCOME MEASURES: Trends in rates of varicella
      related hospitalizations and ambulatory visits and direct medical expenditures
      for hospitalizations and ambulatory visits, analyzed using 1994 and 1995 as the
      prevaccination baseline. RESULTS: From the prevaccination period to 2002,
      hospitalizations due to varicella declined by 88% (from 2.3 to 0.3 per 100,000
      population) and ambulatory visits declined by 59% (from 215 to 89 per 100,000
      population). Hospitalizations and ambulatory visits declined in all age groups,
      with the greatest declines among infants younger than 1 year. Total estimated
      direct medical expenditures for varicella hospitalizations and ambulatory visits
      declined by 74%, from an average of 84.9 million dollars in 1994 and 1995 to 22.1
      million dollars in 2002. CONCLUSION: Since the introduction of the varicella
      vaccination program, varicella hospitalizations, ambulatory visits, and their
      associated expenditures have declined dramatically among all age groups in the
      United States.

PMID- 16106005
TI  - Relationship between time of day, day of week, timeliness of reperfusion, and in
      hospital mortality for patients with acute ST-segment elevation myocardial
      infarction.
AB  - CONTEXT: Understanding how door-to-drug and door-to-balloon times vary by time of
      day and day of week can inform the design of interventions to improve the
      timeliness of reperfusion therapy. OBJECTIVE: To determine the pattern of door-to
      drug and door-to-balloon times by time of day and day of week and whether this
      pattern may affect mortality. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of
      68,439 patients with ST-segment elevation myocardial infarction (STEMI) treated
      with fibrinolytic therapy and 33,647 treated with percutaneous coronary
      intervention (PCI) from 1999 through 2002. We classified patient hospital arrival
      period into regular hours (weekdays, 7 am-5 pm) and off-hours (weekdays 5 pm-7 am
      and weekends). MAIN OUTCOME MEASURES: Geometric mean door-to-drug time for
      fibrinolytic therapy and door-to-balloon time for PCI and all-cause in-hospital
      mortality. All outcomes were adjusted for patient and hospital characteristics.
      RESULTS: Most fibrinolytic therapy (67.9%) and PCI patients (54.2%) were treated
      during off-hours. Door-to-drug times were slightly longer during off-hours (34.3
      minutes) than regular hours (33.2 minutes; difference, 1.0 minute; 95% confidence
      interval [CI], 0.7-1.4; P<.001). In contrast, door-to-balloon times were
      substantially longer during off-hours (116.1 minutes) than regular hours (94.8
      minutes; difference, 21.3 minutes; 95% CI, 20.5-22.2; P<.001). A lower percentage
      of patients met guideline recommended times for door-to-balloon during off-hours
      (25.7%) than regular hours (47%; P<.001). Door-to-balloon times exceeding 120
      minutes occurred much more commonly during off-hours (41.5%) than regular hours
      (27.7%; P<.001). Longer off-hours door-to-balloon times were primarily due to a
      longer interval between obtaining the electrocardiogram and patient arrival at
      the catheterization laboratory (off-hours, 69.8 minutes vs regular hours, 49.1
      minutes; P<.001). This pattern was consistent across all hospital subgroups
      examined. Furthermore, patients presenting during off-hours had significantly
      higher adjusted in-hospital mortality than patients presenting during regular
      hours (odds ratio, 1.07; 95% CI, 1.01-1.14; P = .02). CONCLUSIONS: Presentation
      during off-hours was common and was associated with substantially longer times to
      treatment for PCI but not for fibrinolytic therapy. To achieve the best outcomes,
      hospitals providing PCI during off-hours should commit to doing so in a timely
      manner.

PMID- 16106006
TI  - Acute renal failure in critically ill patients: a multinational, multicenter
      study.
AB  - CONTEXT: Although acute renal failure (ARF) is believed to be common in the
      setting of critical illness and is associated with a high risk of death, little
      is known about its epidemiology and outcome or how these vary in different
      regions of the world. OBJECTIVES: To determine the period prevalence of ARF in
      intensive care unit (ICU) patients in multiple countries; to characterize
      differences in etiology, illness severity, and clinical practice; and to
      determine the impact of these differences on patient outcomes. DESIGN, SETTING,
      AND PATIENTS: Prospective observational study of ICU patients who either were
      treated with renal replacement therapy (RRT) or fulfilled at least 1 of the
      predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals
      in 23 countries. MAIN OUTCOME MEASURES: Occurrence of ARF, factors contributing
      to etiology, illness severity, treatment, need for renal support after hospital
      discharge, and hospital mortality. RESULTS: Of 29 269 critically ill patients
      admitted during the study period, 1738 (5.7%; 95% confidence interval [CI], 5.5%
      6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT.
      The most common contributing factor to ARF was septic shock (47.5%; 95% CI, 45.2%
      49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall
      hospital mortality was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at
      hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent
      risk factors for hospital mortality included use of vasopressors (odds ratio
      [OR], 1.95; 95% CI, 1.50-2.55; P<.001), mechanical ventilation (OR, 2.11; 95% CI,
      1.58-2.82; P<.001), septic shock (OR, 1.36; 95% CI, 1.03-1.79; P = .03),
      cardiogenic shock (OR, 1.41; 95% CI, 1.05-1.90; P = .02), and hepatorenal
      syndrome (OR, 1.87; 95% CI, 1.07-3.28; P = .03). CONCLUSION: In this
      multinational study, the period prevalence of ARF requiring RRT in the ICU was
      between 5% and 6% and was associated with a high hospital mortality rate.

PMID- 16106007
TI  - Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with coronary
      artery disease: meta-analysis of randomized trials.
AB  - CONTEXT: Placement of sirolimus-eluting stents or paclitaxel-eluting stents has
      emerged as the predominant percutaneous treatment strategy in patients with
      coronary artery disease (CAD). Whether there are any differences in efficacy and
      safety between these 2 drug-eluting stents is unclear. OBJECTIVE: To compare
      outcomes of sirolimus-eluting and paclitaxel-eluting coronary stents on the basis
      of data generated by randomized head-to-head clinical trials. DATA SOURCES:
      PubMed and the Cochrane Central Register of Controlled Trials, conference
      proceedings from major cardiology meetings, and Internet-based sources of
      information on clinical trials in cardiology from January 2003 to April 2005.
      STUDY SELECTION: Randomized trials comparing the sirolimus-eluting stent with the
      paclitaxel-eluting stent in patients with CAD reporting the outcomes of interest
      (target lesion revascularization, angiographic restenosis, stent thrombosis,
      myocardial infarction [MI], death, and the composite of death or MI) during a
      follow-up of at least 6 months. DATA EXTRACTION: Two reviewers independently
      identified studies and abstracted data on sample size, baseline characteristics,
      and outcomes of interest. DATA SYNTHESIS: Six trials, including 3669 patients,
      met the selection criteria. No significant heterogeneity was found across trials.
      Target lesion revascularization, the primary outcome of interest, was less
      frequently performed in patients who were treated with the sirolimus-eluting
      stent (5.1%) vs the paclitaxel-eluting stent (7.8%) (odds ratio [OR], 0.64; 95%
      confidence interval [CI], 0.49-0.84; P = .001). Similarly, angiographic
      restenosis was less frequently observed among patients assigned to the sirolimus
      eluting stent (9.3%) vs the paclitaxel-eluting stent (13.1%) (OR, 0.68; 95% CI,
      0.55-0.86; P = .001). Event rates for sirolimus-eluting vs paclitaxel-eluting
      stents were 0.9% and 1.1%, respectively, for stent thrombosis (P = .62); 1.4% and
      1.6%, respectively, for death (P = .56); and 4.9% and 5.8%, respectively, for the
      composite of death or MI (P = .23). CONCLUSIONS: Patients receiving sirolimus
      eluting stents had a significantly lower risk of restenosis and target vessel
      revascularization compared with those receiving paclitaxel-eluting stents. Rates
      of death, death or MI, and stent thrombosis were similar.

PMID- 16106008
TI  - Quantifying the federal minimal risk standard: implications for pediatric
      research without a prospect of direct benefit.
AB  - United States federal regulations allow institutional review boards (IRBs) to
      approve pediatric research that does not offer participants a "prospect of
      direct" benefit only when the risks are minimal or a "minor" increase over
      minimal. The federal regulations define minimal risks based on the risks
      "ordinarily encountered in daily life or during routine physical or psychological
      examinations or tests." In the absence of empirical data, IRB members may assume
      they are familiar with the risks of daily life and with the risks of routine
      examinations and tests and rely on their own intuitive judgment to make these
      assessments. Yet intuitive judgment of risk is subject to systematic errors,
      highlighting the need for empirical data to guide IRB review and approval of
      pediatric research. Current data reveal that car trips pose the highest risk of
      mortality ordinarily encountered by healthy children. On average, these risks are
      approximately 0.06 per million for children aged 14 years and younger, and
      approximately 0.4 per million for children aged 15 through 19 years. Riskier, but
      still ordinary, car trips pose an approximately 0.6 per million chance of death
      for children aged 14 years and younger and an approximately 4 per million chance
      of death for children aged 15 through 19 years. Participation in sports
      represents the upper end of the range of morbidity risks for healthy children.
      For every million instances of playing basketball, approximately 1900 individuals
      will sustain injuries, including 180 broken bones and 58 permanent disabilities.
      These findings suggest IRBs are implementing the federal minimal risk standard
      too cautiously in many cases. These data also raise the question of whether the
      federal minimal risk standard may sometimes fail to provide sufficient protection
      for children, prompting the need to consider alternative standards.

PMID- 16106009
TI  - A 38-year-old woman with fetal loss and hysterectomy.

PMID- 16106010
TI  - A 43-year-old woman with end-stage renal disease, 2 years 6 months later.

PMID- 16106011
TI  - Medical marijuana, American federalism, and the Supreme Court.

PMID- 16106012
TI  - Varicella vaccine, cost-effectiveness analyses, and vaccination policy.

PMID- 16106013
TI  - JAMA patient page. Chickenpox.

PMID- 16106014
TI  - Third biannual report of the Cochrane Haematological Malignancies Group.

PMID- 16106016
TI  - Should screen-detected breast cancers be managed differently?

PMID- 16106015
TI  - Gefitinib versus cetuximab in lung cancer: round one.

PMID- 16106017
TI  - Following positive epidemiologic studies, statins to enter clinical trials for
      cancer prevention.

PMID- 16106018
TI  - Efforts aimed at reducing noise, data overload in microarrays.

PMID- 16106019
TI  - Researchers attempting to define role of cytokines in cancer risk.

PMID- 16106020
TI  - Near-final word on adjuvant chemotherapy for breast cancer is good news.

PMID- 16106021
TI  - Stat bite: Average length of hospital stay by diagnostic category, 2003.

PMID- 16106022
TI  - Reporting recommendations for tumor marker prognostic studies (REMARK).
AB  - Despite years of research and hundreds of reports on tumor markers in oncology,
      the number of markers that have emerged as clinically useful is pitifully small.
      Often, initially reported studies of a marker show great promise, but subsequent
      studies on the same or related markers yield inconsistent conclusions or stand in
      direct contradiction to the promising results. It is imperative that we attempt
      to understand the reasons that multiple studies of the same marker lead to
      differing conclusions. A variety of methodologic problems have been cited to
      explain these discrepancies. Unfortunately, many tumor marker studies have not
      been reported in a rigorous fashion, and published articles often lack sufficient
      information to allow adequate assessment of the quality of the study or the
      generalizability of study results. The development of guidelines for the
      reporting of tumor marker studies was a major recommendation of the National
      Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI
      EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the
      successful CONSORT initiative for randomized trials and for the STARD statement
      for diagnostic studies, we suggest guidelines to provide relevant information
      about the study design, preplanned hypotheses, patient and specimen
      characteristics, assay methods, and statistical analysis methods. In addition,
      the guidelines suggest helpful presentations of data and important elements to
      include in discussions. The goal of these guidelines is to encourage transparent
      and complete reporting so that the relevant information will be available to
      others to help them to judge the usefulness of the data and understand the
      context in which the conclusions apply.

PMID- 16106023
TI  - Differential effects of gefitinib and cetuximab on non-small-cell lung cancers
      bearing epidermal growth factor receptor mutations.
AB  - BACKGROUND: Many patients with non-small-cell lung cancer (NSCLC) who achieve
      radiographic responses to treatment with the epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib have somatic mutations
      in the EGFR tyrosine kinase domain. However, little is known about the efficacy
      of cetuximab, an antibody against the EGFR extracellular domain, in EGFR mutant
      NSCLC. METHODS: NSCLC cell lines carrying wild-type EGFR (A549, H441, and H1666)
      or mutant EGFR (H3255, DFCILU-011, PC-9, and HCC827) were treated with various
      dilutions of gefitinib or cetuximab relative to maximal achievable serum
      concentration. Cell growth was analyzed by the MTS assay, with differences
      between dose-response curves analyzed nonparametrically. Apoptosis was analyzed
      by propidium iodide staining and immunoblotting for PARP. Phosphorylation of EGFR
      and the downstream signaling components ERK1/2 and Akt were analyzed by
      immunoblotting. Statistical tests were two-sided. RESULTS: Growth of NSCLC lines
      with wild-type EGFR was slightly (A549 and H441) or moderately (H1666) inhibited
      by gefitinib and cetuximab, and the effects of the two agents were similar. Both
      agents also induced no (H441) or moderate (H1666) apoptosis in NSCLC cells with
      wild-type EGFR. By contrast, gefitinib was statistically significantly more
      effective than cetuximab at inhibiting growth of EGFR mutant cells (H3255: P =
      .003, DFCILU-011: P = .011, and PC-9: P = .003), and gefitinib-treated EGFR
      mutant cells had higher levels of apoptosis than cetuximab-treated cells (mean
      fold increase in apoptosis by 1 microM of gefitinib and 10 microg/mL of cetuximab
      relative to control, H3255: 8.3 [95% confidence interval {CI} = 4.8 to 11.8] and
      2.1 [95% CI = 2.0 to 2.2], respectively, P = .025; DFCILU-011: 5.7 [95% CI = 5.1
      to 6.3] and. 0.9 [95% CI = 0.3 to 1.5], respectively, P < .001). Gefitinib
      treatment decreased EGFR, ERK1/2, and Akt phosphorylation in EGFR mutant cell
      lines whereas cetuximab had relatively little effect. Both gefitinib and
      cetuximab inhibited the growth of HCC827 cells, but gefitinib inhibited growth to
      a greater extent (P = .003). CONCLUSIONS: EGFR mutations in NSCLC cells are
      associated with sensitivity to gefitinib but not to cetuximab.

PMID- 16106024
TI  - Role of detection method in predicting breast cancer survival: analysis of
      randomized screening trials.
AB  - BACKGROUND: Screening mammography detects breast cancers earlier than those
      detected symptomatically, and so mammographically detected breast cancers tend to
      have better prognoses. The so-called stage shift that results from screen
      detection is subject to lead-time and length biases, and so earlier detection may
      not translate into longer survival. We used data from three large breast cancer
      screening trials--Health Insurance Plan (HIP) of New York and two Canadian
      National Breast Cancer Screening Studies (CNBSS)--to investigate survival
      benefits of breast cancer screening beyond stage shift. We also address whether
      method of detection is an independent prognostic factor in breast cancer.
      METHODS: The HIP trial randomly assigned approximately 62,000 women to screening
      and control groups. The two CNBSS trial cohorts CNBSS-1 and CNBSS-2 included a
      total of 44,970 women in the screening group and 44,961 in the control group.
      After adjusting for stage and other tumor characteristics in a Cox proportional
      hazards model, survival distributions were compared by method of breast cancer
      detection with both univariate and multivariable analyses. All P values are two
      sided. RESULTS: Breast cancers detected by screening mammography had a shift in
      stage distribution to earlier stages (for HIP, P < .001; for CNBSS-1, P = .03;
      and for CNBSS-2, P < .001). After adjusting for tumor size, lymph node status,
      and disease stage in a Cox proportional hazards model, method of detection was a
      statistically significant independent predictor of disease-specific survival.
      Patients with interval cancers had a 53% (95% confidence interval [CI] = 17% to
      100%) greater hazard of death from breast cancer than patients with screen
      detected cancers, and patients with cancer in the control groups had a 36% (95%
      CI = 10% to 68%) greater hazard of death than patients with screen-detected
      cancer. CONCLUSION: There was an apparent survival benefit beyond stage shift for
      patients with screen-detected breast cancers compared with patients with breast
      cancers detected otherwise. Method of detection appears to be an important
      prognostic factor, even after adjusting for known tumor characteristics. This
      finding suggests that clinical trialists should routinely collect information
      about method of detection.

PMID- 16106025
TI  - Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study.
AB  - BACKGROUND: Men with Klinefelter syndrome have one or more extra X chromosomes
      and have endocrine abnormalities. Case reports have led to suggestions that men
      with Klinefelter syndrome have elevated risks of several cancers, but published
      cohort studies have been relatively small. We conducted a nationwide cohort study
      to examine these risks. METHODS: We followed a cohort of 3518 men who had been
      cytogenetically diagnosed with Klinefelter syndrome in Britain from 1959 through
      2002 and compared their cancer incidence and mortality with that of men in the
      national population. All statistical tests were two-sided. RESULTS: The
      standardized mortality ratio (SMR) for all cancers was 1.2 (95% confidence
      interval [CI] = 1.0 to 1.4). Compared with the general population, men with
      Klinefelter syndrome had higher mortality from lung cancer (SMR = 1.5, 95% CI =
      1.0 to 2.0), breast cancer (SMR = 57.8, 95% CI = 18.8 to 135.0), and non-Hodgkin
      lymphoma (SMR = 3.5, 95% CI = 1.6 to 6.6) and lower mortality from prostate
      cancer (SMR = 0, 95% CI = 0 to 0.7). The standardized mortality ratios were
      particularly high for breast cancer among men with 47,XXY mosaicism (SMR = 222.8,
      95% CI = 45.9 to 651.0) and for non-Hodgkin lymphoma among men with a 48,XXYY
      constitution (SMR = 36.7, 95% CI = 4.4 to 132.5). The cancer incidence data
      corroborated these associations. CONCLUSIONS: These results support a hormonal
      etiology for breast cancer in men and for prostate cancer and suggest that men
      with Klinefelter syndrome may be at substantially elevated risks for non-Hodgkin
      lymphoma, breast cancer, and, perhaps, lung cancer.

PMID- 16106026
TI  - Explaining black-white differences in receipt of recommended colon cancer
      treatment.
AB  - BACKGROUND: Black-white disparities exist in receipt of recommended medical care,
      including colorectal cancer treatment. This retrospective cohort study examines
      the degree to which health systems (e.g., physician, hospital) factors explain
      black-white disparities in colon cancer care. METHODS: Data from the
      Surveillance, Epidemiology, and End Results program; Medicare claims; the
      American Medical Association Masterfile; and hospital surveys were linked to
      examine chemotherapy receipt after stage III colon cancer resection among 5294
      elderly (> or = 66 years of age) black and white Medicare-insured patients.
      Logistic regression analysis was used to identify factors associated with black
      white differences in chemotherapy use. All statistical tests were two-sided.
      RESULTS: Black and white patients were equally likely to consult with a medical
      oncologist, but among patients who had such a consultation, black patients were
      less likely than white patients (59.3% versus 70.4%, difference = 10.9%, 95%
      confidence interval [CI] = 5.1% to 16.4%, P < .001) to receive chemotherapy. This
      black-white disparity was highest among patients aged 66-70 years (black patients
      65.7%, white patients 86.3%, difference = 20.6%, 95% CI = 10.7% to 30.4%, P <
      .001) and decreased with age. The disparity among patients aged 66-70 years also
      remained statistically significant in the regression analysis. Overall, patient,
      physician, hospital, and environmental factors accounted for approximately 50% of
      the disparity in chemotherapy receipt among patients aged 66-70 years; surgical
      length of stay and neighborhood socioeconomic status accounted for approximately
      27% of the disparity in this age group, and health systems factors accounted for
      12%. CONCLUSIONS: Black and white Medicare-insured colon cancer patients have an
      equal opportunity to learn about adjuvant chemotherapy from a medical oncologist
      but do not receive chemotherapy equally. Little disparity was explained by health
      systems; more was explained by illness severity, social support, and environment.
      Further qualitative research is needed to understand the factors that influence
      the lower receipt of chemotherapy by black patients.

PMID- 16106027
TI  - Cetuximab therapy and symptomatic hypomagnesemia.
AB  - We report that patients treated with cetuximab, a monoclonal antibody against the
      epithelial growth factor receptor (EGFR), occasionally develop a magnesium
      wasting syndrome with inappropriate urinary excretion. We first observed this
      phenomenon in a 34-year-old male patient with metastatic colorectal cancer who
      developed profound fatigue and symptomatic hypocalcemia and hypomagnesemia while
      on cetuximab plus irinotecan therapy. Other medications with the potential to
      cause magnesium wasting had not been administered. Intravenous magnesium
      supplementation was required for the duration of cetuximab therapy, but
      electrolyte abnormalities resolved after discontinuation of treatment. This case
      prompted review of serum chemistry reports for a consecutive case series of 154
      colorectal cancer patients treated with cetuximab. Thirty-four patients (22%) had
      at least one serum magnesium measurement during cetuximab treatment, and six had
      grade 3 (< 0.9 mg/dL) and two had grade 4 (< 0.7 mg/dL) hypomagnesemia. Because
      EGFR is strongly expressed in the kidney, particularly in the ascending limb of
      the loop of Henle where 70% of filtered magnesium is reabsorbed, EGFR blockade
      may interfere with magnesium transport. Because symptoms may be rapidly
      ameliorated with supplementation, we suggest that, when fatigue or hypocalcemia
      is encountered during cetuximab therapy, serum magnesium level be measured and
      repleted as necessary.

PMID- 16106028
TI  - Re: Medroxyprogesterone acetate and metastases: of mice and (wo)men.

PMID- 16106029
TI  - Re: Lessons from controversy: Ovarian cancer screening and serum proteomics.

PMID- 16106031
TI  - Tools and strategies for physiological genomics: the Rat Genome Database.
AB  - The broad goal of physiological genomics research is to link genes to their
      functions using appropriate experimental and computational techniques. Modern
      genomics experiments enable the generation of vast quantities of data, and
      interpretation of this data requires the integration of information derived from
      many diverse sources. Computational biology and bioinformatics offer the ability
      to manage and channel this information torrent. The Rat Genome Database (RGD;
      http://rgd.mcw.edu) has developed computational tools and strategies specifically
      supporting the goal of linking genes to their functional roles in rat and, using
      comparative genomics, to human and mouse. We present an overview of the database
      with a focus on these unique computational tools and describe strategies for the
      use of these resources in the area of physiological genomics.

PMID- 16106032
TI  - Gene expression analysis suggests that EBF-1 and PPARgamma2 induce adipogenesis
      of NIH-3T3 cells with similar efficiency and kinetics.
AB  - Differentiation of multipotent mesenchymal stem cells into lipid-accumulating
      adipocytes is a physiological process induced by transcription factors in
      combination with hormonal stimulation. We have used Affymetrix microarrays to
      compare the adipogenic differentiation pathways of NIH-3T3 fibroblasts induced to
      undergo in vitro differentiation by ectopic expression of early B cell factor
      (EBF)-1 or peroxisome proliferator-activated receptor (PPAR)gamma2. These
      experiments revealed that commitment to the adipogenic pathway in the NIH-3T3
      cells was not reflected in gene expression until 4 days after induction of
      differentiation. Furthermore, gene expression patterns at the earlier time points
      after stimulation indicated that EBF-1 and PPARgamma2 induced different sets of
      genes, while the similarities increased upon differentiation, and that several
      genes linked to adipocyte differentiation were also transiently induced in the
      vector-transduced cells. These data suggest that the initial activation of genes
      associated with adipocyte development is independent of commitment to the
      adipogenic pathway and that EBF-1 and PPARgamma2 induce adipocyte differentiation
      with comparable kinetics and efficiency.

PMID- 16106033
TI  - Late restenosis in patients receiving a polymer-coated sirolimus-eluting stent.

PMID- 16106034
TI  - Contribution of the basolateral isoform of the Na-K-2Cl- cotransporter
      (NKCC1/BSC2) to renin secretion.
AB  - Acute administration of loop diuretics like furosemide leads to a stimulation of
      renin secretion, an effect thought to result from inhibition of Na-K-2Cl
      cotransporter (NKCC2)-mediated salt transport at the luminal surface of the
      macula densa (MD). However, loop diuretics also inhibit NKCC1, the second isoform
      of the Na-K-2Cl cotransporter, with similar potency. In the present study, we
      examined the influence of furosemide on renin secretion in NKCC1-deficient mice
      to distinguish between effects of the loop diuretic involving NKCC2 and, by
      implication, the MD pathway, and effects that might occur via inhibition of
      NKCC1. Baseline plasma renin concentration (PRC) was 1,212 +/- 211 in NKCC1+/+ (n
      = 13) and 3,851 +/- 579 ng ANG I.ml(-1).h(-1) in NKCC1-/- mice (n = 14; P =
      0.00024). Acute administration of furosemide (50 mg/kg i.p.) increased PRC
      significantly to 9,324 +/- 1,018 ng ANG I.ml(-1).h(-1) in NKCC1+/+ (n = 13; P <
      0.0001 compared with basal) and to 14,188 +/- 2,274 ng ANG I.ml(-1).h(-1) in
      NKCC1-/- mice [n = 14; P = 0.0002 compared with basal; P = 0.034 compared with
      wild-type (WT) plus furosemide]. Renin mRNA expression was about threefold higher
      in NKCC1-/- compared with WT mice. There was considerable recruitment of granular
      cells to upstream regions of afferent arterioles in NKCC1-/- mice. Patch-clamp
      studies in single juxtaglomerular granular (JG) cells from WT mice showed an
      approximately 10% increase in membrane capacitance during incubation with
      furosemide (10(-4) M), indicating a direct effect of the loop diuretic on renin
      secretion. No effect of furosemide on membrane capacitance was observed in JG
      cells from NKCC1-deficient mice. Furosemide (10(-3) M) significantly stimulated
      renin release from primary cultures of JG cells from WT mice, whereas no response
      was observed in NKCC1-/- mice. Our data suggest that a functional NKCC1
      suppresses basal renin release, at least in part, through a direct effect on JG
      cells.

PMID- 16106035
TI  - Role of integrin alpha1beta1 in the regulation of renal medullary osmolyte
      concentration.
AB  - The mechanism by which cells sense extracellular tonicity and trigger the
      accumulation of protective organic osmolytes is poorly understood. It has been
      proposed that changes in cell volume following alteration of extracellular
      toncity are important initiators of signaling events that lead to osmolyte
      accumulation. Because the extracellular matrix receptors integrins are linked to
      the cytoskeleton and can transduce signals that alter cell behavior, we
      investigated the role of these receptors in the modulation of osmolyte
      accumulation in the kidney medulla under different osmotic conditions. We show
      that integrin alpha1-null mice have impaired ability to accumulate organic
      osmolytes in the inner medulla due to altered signaling and decreased induction
      of osmolyte transporters or aldose reductase gene transcription. Utilizing inner
      medullary collecting duct cells, we demonstrate that the lack of integrin
      alpha1beta1 results in an impaired ability to induce the tonicity enhancer
      binding protein TonEBP under hypertonic conditions. Furthermore, under the same
      conditions, integrin alpha1-null cells show prolonged ERK1/2 phosphorylation and
      decreased inositol uptake compared with control cells. The reduction of inositol
      uptake is significantly reversed by treatment with the MEK inhibitor PD-98059.
      Finally, integrin alpha1-null mice develop morphological changes of early tubular
      necrosis and increased apoptosis of renal medullary cells following dehydration.
      Together, these results show that integrin alpha1beta1 is an important mediator
      of the compatible osmolyte response in the medulla of the mammalian kidney.

PMID- 16106036
TI  - Cyclic arginine-glycine-aspartic acid peptide inhibits macrophage infiltration of
      the kidney and carotid artery lesions in apo-E-deficient mice.
AB  - Interactions of leukocytes with the vascular endothelium culminating in their
      diapedesis represent not only a crucial event in immune surveillance and defense
      but are also critically involved in the pathogenesis of many inflammatory
      diseases, including atherosclerosis. Our previous in vitro studies using atomic
      force microscopy measurement of monocyte-endothelial cell interaction have
      demonstrated that a cyclic arginine-glycine-aspartic acid peptide (cRGD)
      inhibited their adhesion through very late antigen (alpha4beta1-integrin; VLA4)
      vascular cell adhesion molecule-1 by 60% with the IC50 = 100 nM. To elucidate the
      potential efficacy of this peptide in vivo in preventing atherogenesis,
      experiments were performed in apolipoprotein E (ApoE)-deficient (-/-) mice fed a
      Western diet and receiving chronic treatment with cRGD peptide for 2-4 wk. In
      addition, some animals were subjected to a temporary carotid artery ligation
      while receiving the above treatment. Formation of fatty streaks and infiltration
      of the vascular wall with macrophages were not affected by cRGD treatment.
      Infiltration of the carotid artery postligation was significantly reduced in the
      cRGD-treated animals, as was the lipid accumulation. Furthermore, cRGD-treated
      ApoE-/- mice exhibited significantly lesser macrophage infiltration and lipid
      accumulation in the kidneys, the site of the highest expression of VLA4. These
      data demonstrated that cRGD peptide is a potent inhibitor of monocyte/macrophage
      infiltration of the injured macrovasculature and of the renal microvasculature,
      where it results in the attenuation of lipid accumulation. Formation of fatty
      streaks in the aortic root was not inhibitable by this treatment.

PMID- 16106037
TI  - Bid deficiency ameliorates ischemic renal failure and delays animal death in
      C57BL/6 mice.
AB  - Tubular cell apoptosis is involved in ischemic renal failure, but the underlying
      mechanism is unclear. Bid, a proapoptotic Bcl-2 family protein, may regulate the
      intrinsic as well as the extrinsic pathway of apoptosis. In vivo, Bid is most
      abundantly expressed in the kidneys. However, the role played by Bid in renal
      pathophysiology is unknown. Our recent work demonstrated Bid activation during
      renal ischemia-reperfusion. The current study has determined the role of Bid in
      ischemic renal injury and renal failure using Bid-deficient mice. In wild-type
      C57BL/6 mice, Bid was proteolytically processed into active forms during renal
      ischemia-reperfusion, which subsequently targeted mitochondria. This was
      accompanied by the development of tissue damage and severe renal failure, showing
      serum creatinine of 3.0 mg/dl after 48 h of reperfusion. The same ischemic insult
      induced acute renal failure in Bid-deficient mice, which was nonetheless less
      severe than the wild-type, showing 1.3 mg/dl serum creatinine. In addition, Bid
      deficiency attenuated tubular disruption, tubular cell apoptosis, and caspase-3
      activation during 48 h of reperfusion. Compared with wild-type, animal death
      following renal ischemia was delayed in Bid-deficient mice. Collectively, the
      results suggest a role for Bid in ischemic renal injury and renal failure.

PMID- 16106038
TI  - Expression and localization of N-domain ANG I-converting enzymes in mesangial
      cells in culture from spontaneously hypertensive rats.
AB  - The angiotensin-converting enzyme (ACE) profile in urine of hypertensive patients
      and spontaneously hypertensive rats (SHR; 90- and 65-kDa N-domain ACEs) is
      different from that of healthy subjects and Wistar rats (190 and 65 kDa). In
      addition, four ACE isoforms were purified from mesangial cells (MC) of Wistar
      rats in the intracellular compartment (130 and 68 kDa) and as secreted forms (130
      and 60 kDa). We decided to characterize ACE forms from SHR MC in culture.
      Analysis of the ACE gene showed that SHR MC are able to express ACE mRNA. The
      concentrated medium and cell homogenate were separately purified by gel
      filtration and then subjected to lisinopril-Sepharose chromatography. The
      molecular masses of purified enzymes, 90 kDa for ACEm1A and 65 kDa for ACEm2A
      (secreted enzymes) and 90 kDa for ACEInth1A and 65 kDa for ACEInth2A
      (intracellular), were different from those of Wistar MC. The purified enzymes are
      Cl- dependent, inhibited by enalaprilat and captopril, and able to hydrolyze
      AcSDKP. Immunofluorescence and cell fractionation followed by Western blotting
      showed predominant immunoreaction of the 9B9 antiserum for N-domain ACE in the
      nuclei. The N-domain ACE was localized in the glomerulus from Wistar rats and
      SHR. ANG II and ANG-(1-7) were localized in the cell cytoplasm and nuclei. The 90
      kDa N-domain ACE, described recently as a possible genetic marker of
      hypertension, was found inside the cell nuclei of SHR MC colocalized with ANG II
      and ANG-(1-7). The presence of ANG II in the cell nuclei could suggest an
      important role for this peptide in the transcription of new genes.

PMID- 16106039
TI  - Enhanced superoxide generation modulates renal function in ANG II-induced
      hypertensive rats.
AB  - This study was performed to examine the role of superoxide formation in the
      regulation of renal hemodynamic and excretory function and to assess its
      contribution in the pathogenesis of ANG II-dependent hypertension. Renal
      responses to acute intra-arterial infusion of the O2(-) scavenger tempol (50
      microg x min(-1) x 100 g body wt(-1)) with or without catalase (1,500 U x min(-1)
      x 100 g(-1); both native and polyethylene glycol-catalase), which reduces H2O2,
      were evaluated in anesthetized male Sprague-Dawley rats treated chronically with
      ANG II (65 ng/min) for 2 wk and compared with nontreated control rats. In ANG II
      treated hypertensive rats, tempol caused increases in medullary (13 +/- 2%),
      cortical (5 +/- 2%), and total renal blood flow (9 +/- 2%) without altering
      systemic arterial pressure. There were also increases in glomerular filtration
      rate (9 +/- 2%), urine flow (17 +/- 4%), and sodium excretion (26 +/- 5%).
      However, tempol infusion in nontreated normotensive rats did not cause
      significant changes in any of these renal parameters. Coinfusion of catalase with
      tempol did not alter the responses observed with tempol alone, indicating that
      the observed renal responses to tempol in ANG II-treated rats were attributed to
      its O2(-) scavenging effects without the involvement of H2O2. Tempol infusion
      also significantly decreased 8-isoprostane excretion in ANG II-treated rats (39
      +/- 6%) without changes in H2O2 excretion. However, coinfusion of catalase
      reduced H2O2 excretion in both ANG II-treated (41 +/- 6%) and nontreated rats (28
      +/- 5%). These data demonstrate that enhanced generation of O2(-) modulates renal
      hemodynamic and tubular reabsorptive function, possibly leading to sodium
      retention and thus contributing to the pathogenesis of ANG II-induced
      hypertension.

PMID- 16106040
TI  - Branching ducts similar to mesonephric ducts or ureteric buds in teratomas
      originating from mouse embryonic stem cells.
AB  - Ureteric bud epithelial cells and metanephric mesenchymal cells that comprise the
      metanephric kidney primordium are capable of producing nephrons and collecting
      ducts through reciprocal inductive interaction. Once these cells are induced from
      pluripotent embryonic stem (ES) cells, they have the potential to become powerful
      tools in the regeneration of kidney tissues. In this study, we investigated these
      renal primordial cells and structures in mouse ES cell outgrowths and their
      transplants. Gene expression essential for early kidney development was examined
      by RT-PCR in embryoid body (EB) outgrowths and their transplants in adult mice.
      Histochemical detection of kidney primordial structures and gene expression
      analysis coupled with laser microdissection were performed in transplant tissues.
      RT-PCR analysis detected gene expression of Pax-2, Lim-1, c-Ret, Emx2, Sall1, WT
      1, Eya-1, GDNF, and Wnt-4 in the EB outgrowths from days 6-9 of expansion onward,
      and also in the teratoma tissues 14 and 28 days after transplantation.
      Histochemical analysis 14 days after transplantation showed that some ducts were
      positive for Pax-2, endo A cytokeratin, kidney-specific cadherin, and Dolichos
      biflorus agglutinin and that dichotomous branching of these ducts had occurred.
      These staining patterns and morphological features are intrinsic for mesonephric
      ducts and ureteric buds. In long-term survival of 28 days, Pax-2-immunoreactivity
      disappeared in some renal primordia-like structures, indicating their
      differentiation. Some ducts were accompanied by mesonephric nephron-like
      convoluted tubules. RT-PCR analysis of those structures collected by
      microdissection confirmed that they expressed kidney development-related genes.
      In conclusion, these data suggest the potential of ES cells to produce renal
      primordial duct structures and provides an insight into the regeneration of
      kidney tissues.

PMID- 16106041
TI  - Methylation-specific MLPA (MS-MLPA): simultaneous detection of CpG methylation
      and copy number changes of up to 40 sequences.
AB  - Copy number changes and CpG methylation of various genes are hallmarks of tumor
      development but are not yet widely used in diagnostic settings. The recently
      developed multiplex ligation-dependent probe amplification (MLPA) method has
      increased the possibilities for multiplex detection of gene copy number
      aberrations in a routine laboratory. Here we describe a novel robust method: the
      methylation-specific MLPA (MS-MLPA) that can detect changes in both CpG
      methylation as well as copy number of up to 40 chromosomal sequences in a simple
      reaction. In MS-MLPA, the ligation of MLPA probe oligonucleotides is combined
      with digestion of the genomic DNA-probe hybrid complexes with methylation
      sensitive endonucleases. Digestion of the genomic DNA-probe complex, rather than
      double-stranded genomic DNA, allowed the use of DNA derived from the formalin
      treated paraffin-embedded tissue samples, enabling retrospective studies. To
      validate this novel method, we used MS-MLPA to detect aberrant methylation in DNA
      samples of patients with Prader-Willy syndrome, Angelman syndrome or acute
      myeloid leukemia.

PMID- 16106042
TI  - Ancestral paralogs and pseudoparalogs and their role in the emergence of the
      eukaryotic cell.
AB  - Gene duplication is a crucial mechanism of evolutionary innovation. A substantial
      fraction of eukaryotic genomes consists of paralogous gene families. We assess
      the extent of ancestral paralogy, which dates back to the last common ancestor of
      all eukaryotes, and examine the origins of the ancestral paralogs and their
      potential roles in the emergence of the eukaryotic cell complexity. A
      parsimonious reconstruction of ancestral gene repertoires shows that 4137
      orthologous gene sets in the last eukaryotic common ancestor (LECA) map back to
      2150 orthologous sets in the hypothetical first eukaryotic common ancestor (FECA)
      [paralogy quotient (PQ) of 1.92]. Analogous reconstructions show significantly
      lower levels of paralogy in prokaryotes, 1.19 for archaea and 1.25 for bacteria.
      The only functional class of eukaryotic proteins with a significant excess of
      paralogous clusters over the mean includes molecular chaperones and proteins with
      related functions. Almost all genes in this category underwent multiple
      duplications during early eukaryotic evolution. In structural terms, the most
      prominent sets of paralogs are superstructure-forming proteins with repetitive
      domains, such as WD-40 and TPR. In addition to the true ancestral paralogs which
      evolved via duplication at the onset of eukaryotic evolution, numerous
      pseudoparalogs were detected, i.e. homologous genes that apparently were acquired
      by early eukaryotes via different routes, including horizontal gene transfer
      (HGT) from diverse bacteria. The results of this study demonstrate a major
      increase in the level of gene paralogy as a hallmark of the early evolution of
      eukaryotes.

PMID- 16106043
TI  - Potentiation of gene targeting in human cells by expression of Saccharomyces
      cerevisiae Rad52.
AB  - When exogenous DNA is stably introduced in mammalian cells, it is typically
      integrated in random positions, and only a minor fraction enters a pathway of
      homologous recombination (HR). The complex Rad51/Rad52 is a major player in the
      management of exogenous DNA in eukaryotic organisms and plays a critical role in
      the choice of repair system. In Saccharomyces cerevisiae, the pathway of choice
      is HR, mediated by Rad52 (ScRad52), which differs slightly from its human
      homologue. Here, we present an approach that utilizes ScRad52 to enhance HR in
      human cells containing a specific substrate for recombination. Clones of HeLa
      cells were produced expressing functional ScRad52. These cells showed enhanced
      resistance to DNA damaging treatments and revealed a different distribution of
      Rad51 foci (a marker of recombination complex formation). More significantly,
      ScRad52 expression resulted in an up to 37-fold increase in gene targeting by HR.
      In the same cells, random integration of exogenous DNA was significantly reduced,
      consistent with the view that HR and non-homologous end joining are alternative
      competing pathways. Expression of ScRad52 could offer a major improvement for
      experiments requiring gene targeting by HR, both in basic research and in gene
      therapy studies.

PMID- 16106044
TI  - Not so crystal clear: the structure of the human telomere G-quadruplex in
      solution differs from that present in a crystal.
AB  - The structure of human telomere DNA is of intense interest because of its role in
      the biology of both cancer and aging. The sequence [5'-AGGG(TTAGGG)3] has been
      used as a model for telomere DNA in both NMR and X-ray crystallographic studies,
      the results of which show dramatically different structures. In Na+ solution, NMR
      revealed an antiparallel G-quadruplex structure that featured both diagonal and
      lateral TTA loops. Crystallographic studies in the presence of K+ revealed a
      flattened, propeller-shaped structure featuring a parallel-stranded G-quadruplex
      with symmetrical external TTA loops. We report the results of biophysical
      experiments in solution and computational studies that are inconsistent with the
      reported crystal structure, indicating that a different structure exists in K+
      solutions. Sedimentation coefficients were determined experimentally in both Na+
      and K+ solutions and were compared with values calculated using bead models for
      the reported NMR and crystal structures. Although the solution NMR structure
      accurately predicted the observed S-value in Na+ solution, the crystal structure
      predicted an S-value that differed dramatically from that experimentally observed
      in K+ solution. The environments of loop adenines were probed by quantitative
      fluorescence studies using strategic and systematic single-substitutions of 2
      aminopurine for adenine bases. Both fluorescence intensity and quenching
      experiments in K+ yielded results at odds with quantitative predictions from the
      reported crystal structure. Circular dichroism and fluorescence quenching studies
      in the presence of the crowding agent polyethylene glycol showed dramatic changes
      in the quadruplex structure in K+ solutions, but not in Na+ solutions, suggesting
      that the crystal environment may have selected for a particular conformational
      form. Molecular dynamics simulations were performed to yield model structures for
      the K+ quadruplex form that are consistent with our biophysical results and with
      previously reported chemical modification studies. These models suggest that the
      biologically relevant structure of the human telomere quadruplex in K+ solution
      is not the one determined in the published crystalline state.

PMID- 16106045
TI  - Ceramide- and ERK-dependent pathway for the activation of CCAAT/enhancer binding
      protein by interleukin-1beta in hepatocytes.
AB  - Interleukin-1beta (IL-1beta) is a major inducer of liver acute-phase protein
      expression in response to infection. Several transcription factors, including
      CCAAT/enhancer binding protein (C/EBP), are known mediators in this process,
      although the mechanisms by which they modulate IL-1beta's action are not
      completely understood. Activation of sphingomyelinase (SMase) and the subsequent
      generation of ceramide are early steps in the IL-1beta signaling cascade. In this
      study, we investigate the role of ceramide in the IL-1beta regulation of C/EBP in
      primary hepatocytes. The C/EBP DNA binding activity was found to increase in a
      dose-dependent manner after stimulation with IL-1beta and exogenous addition of
      C2-ceramide or treatment with SMase. These changes were accompanied by an
      increase in the nuclear content of C/EBPbeta. Both IL-1beta and ceramide led to
      extracellular signal-regulated kinase 1/2 (ERK1/2) activation as early as 15 min
      after treatment. Furthermore, the increase of cellular ceramide content resulted
      in increased phosphorylation of C/EBPbeta at serine 105 at later time points.
      Concurrently, the cytosolic levels of C/EBPbeta decreased, suggesting that IL
      1beta and ceramide induced nuclear translocation of C/EBPbeta. Ceramide-induced
      C/EBPbeta phosphorylation, translocation, and DNA binding were suppressed by the
      addition of PD98059, an inhibitor of ERK1/2 phosphorylation. These results
      suggest that ceramide and ERK mediate a pathway in the IL-1beta signaling
      cascade, which results in rapid posttranslational activation of C/EBPbeta.

PMID- 16106046
TI  - Structure and function of lysosomal phospholipase A2: identification of the
      catalytic triad and the role of cysteine residues.
AB  - Lysosomal phospholipase A2 (LPLA2) is an acidic phospholipase that is highly
      expressed in alveolar macrophages and that may play a role in the catabolism of
      pulmonary surfactant. The primary structure found in LCAT is conserved in LPLA2,
      including three amino acid residues potentially required for catalytic activity
      and four cysteine residues. LPLA2 activity was measured in COS-7 cells
      transfected with c-myc-conjugated mouse LPLA2 (mLPLA2) or mutated LPLA2. Single
      alanine substitutions in the catalytic triad resulted in the elimination of LPLA2
      activity. Four cysteine residues (C65, C89, C330, and C371), conserved between
      LPLA2 and LCAT, were replaced with alanine. Quadruple mutations at C65, C89,
      C330, and C371, double mutations at C65 and C89, and a single mutation at C65 or
      C89 resulted in the elimination of activity. Double mutations at C330 and C371
      and a single mutation at C330 or C371 resulted in a partial reduction of
      activity. Thus, the presence of a disulfide bond between C330 and C371 is not
      required for LPLA2 activity. We propose that one disulfide bond between C65 and
      C89 and free cysteine residues at C330 and C371 and the triad, serine-198,
      aspartic acid-360, and histidine-392, are required for the full expression of
      mLPLA2 activity.

PMID- 16106047
TI  - Peroxisome proliferator-activated receptor alpha is required for feedback
      regulation of highly unsaturated fatty acid synthesis.
AB  - Delta6 desaturase (D6D), the rate-limiting enzyme for highly unsaturated fatty
      acid (HUFA) synthesis, is induced by essential fatty acid-deficient diets. Sterol
      regulatory element-binding protein-1c (SREBP-1c) in part mediates this induction.
      Paradoxically, D6D is also induced by ligands of peroxisome proliferator
      activated receptor alpha (PPARalpha). Here, we report a novel physiological role
      of PPARalpha in the induction of genes specific for HUFA synthesis by essential
      fatty acid-deficient diets. D6D mRNA induction by essential fatty acid-deficient
      diets in wild-type mice was diminished in PPARalpha-null mice. This impaired D6D
      induction in PPARalpha-null mice was not attributable to feedback suppression by
      tissue HUFAs because PPARalpha-null mice had lower HUFAs in liver phospholipids
      than did wild-type mice. Furthermore, PPARalpha-responsive genes were induced in
      wild-type mice under essential fatty acid deficiency, suggesting the generation
      of endogenous PPARalpha ligand(s). Contrary to genes for HUFA synthesis, the
      induction of other lipogenic genes under essential fatty acid deficiency was
      higher in PPARalpha-null mice than in wild-type mice even though mature SREBP-1c
      protein did not differ between the genotypes. The expression of PPARgamma was
      markedly increased in PPARalpha-null mice and might have contributed to the
      induction of genes for de novo lipogenesis. Our study suggests that PPARalpha,
      together with SREBP-1c, senses HUFA status and confers pathway-specific induction
      of HUFA synthesis by essential fatty acid-deficient diets.

PMID- 16106048
TI  - Lipoprotein metabolism of pregnant women is associated with both their genetic
      polymorphisms and those of their newborn children.
AB  - To explore whether the placenta contributes to the lipoprotein metabolism of
      pregnant women, we took advantage of the fact that placental proteins are encoded
      from the fetal genome and examined the associations between lipids of 525
      pregnant women and the presence, in their newborns, of genetic polymorphisms of
      LPL and apolipoprotein E (APOE), two genes expressed in placenta. After
      adjustment for maternal polymorphisms, newborn LPL*S447X was associated with
      lower triglycerides (-21 +/- 9 mg/dl), lower LDL-cholesterol (LDL-C; -12 +/- 5
      mg/dl), lower apoB (-14 +/- 4 mg/dl), higher HDL-C (5 +/- 2 mg/dl), and higher
      apoA-I (9 +/- 4 mg/dl) in their mothers; newborn LPL*N291S was associated with
      higher maternal triglycerides (114 +/- 31 mg/dl); and newborn APOE*E2 (compared
      to E3E3) was associated with higher maternal LDL-C (14 +/- 6 mg/dl) and higher
      maternal apoB (14 +/- 5 mg/dl). These associations (all P < 0.05) were
      independent of polymorphisms carried by the mothers and of lipid concentrations
      in newborns and were similar in amplitude to the associations between maternal
      polymorphisms and maternal lipids. Such findings support the active role of
      placental LPL and APOE in the metabolism of maternal lipoproteins and suggest
      that fetal genes may modulate the risk for problems related to maternal
      dyslipidemia (preeclampsia, pancreatitis, and future cardiovascular disease).

PMID- 16106049
TI  - Decreased adiponectin levels in familial combined hyperlipidemia patients
      contribute to the atherogenic lipid profile.
AB  - Familial combined hyperlipidemia (FCH) is characterized by increased levels of
      total cholesterol, triglycerides, and/or apolipoprotein B. Other features of FCH
      are obesity and insulin resistance. Adiponectin is a secretory product of the
      adipose tissue. Low levels of adiponectin are associated with insulin resistance
      and accelerated atherosclerosis. The aim of this study was to determine whether
      decreased adiponectin levels are associated with FCH and its phenotypes. The
      study population comprised 644 subjects, including 158 patients with FCH. Serum
      adiponectin levels were determined using a commercially available ELISA. For both
      males and females, the mean adiponectin level (microg/ml) was significantly lower
      in FCH patients [2.0 (1.8-2.2) and 2.5 (2.3-2.8), respectively] compared with
      normolipidemic relatives [2.3 (2.2-2.5) and 3.1 (2.8-3.3), respectively] and
      spouses [2.4 (2.1-2.7) and 3.2 (2.8-3.6), respectively]. These differences remain
      significant after adjusting for waist circumference and insulin resistance. Low
      adiponectin level in FCH patients was a superior independent predictor of the
      atherogenic lipid profile, including high triglyceride levels, low HDL
      cholesterol levels, and the amount of small, dense LDL present, compared with
      both obesity and insulin resistance. Low adiponectin levels may contribute to the
      atherogenic lipid profile in FCH, independent of insulin resistance and obesity,
      as measured by waist circumference. This finding implies a role of adipose tissue
      metabolism in the pathophysiology of FCH.

PMID- 16106050
TI  - A human skin multifunctional O-acyltransferase that catalyzes the synthesis of
      acylglycerols, waxes, and retinyl esters.
AB  - Acyl-CoA-dependent O-acyltransferases catalyze reactions in which fatty acyl-CoAs
      are joined to acyl acceptors containing free hydroxyl groups to produce neutral
      lipids. In this report, we characterize a human multifunctional O-acyltransferase
      (designated MFAT) that belongs to the acyl-CoA:diacylglycerol acyltransferase
      2/acyl-CoA:monoacylglycerol acyltransferase (MGAT) gene family and is highly
      expressed in the skin. Membranes of insect cells and homogenates of mammalian
      cells overexpressing MFAT exhibited significantly increased MGAT, acyl-CoA:fatty
      acyl alcohol acyltransferase (wax synthase), and acyl-CoA:retinol acyltransferase
      (ARAT) activities, which catalyze the synthesis of diacylglycerols, wax
      monoesters, and retinyl esters, respectively. Furthermore, when provided with the
      appropriate substrates, intact mammalian cells overexpressing MFAT accumulated
      more waxes and retinyl esters than control cells. We conclude that MFAT is a
      multifunctional acyltransferase that likely plays an important role in lipid
      metabolism in human skin.

PMID- 16106051
TI  - Downregulation of liver X receptor-alpha in mouse kidney and HK-2 proximal
      tubular cells by LPS and cytokines.
AB  - The acute-phase response (APR) suppresses type II nuclear hormone receptors and
      alters the expression of their target genes involved in lipid metabolism in the
      liver and heart. Therefore, we examined the expression of liver X
      receptor/retinoid X receptor (LXR/RXR) and their target genes in kidney from mice
      treated with lipopolysaccharide (LPS) and in human proximal tubular HK-2 cells
      treated with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF
      alpha). We found that LXRalpha and RXRalpha expression was suppressed by LPS in
      kidney and by IL-1beta or TNF-alpha in HK-2 cells. The decrease in
      LXRalpha/RXRalpha expression was associated with a decrease in the expression of
      several LXRalpha target genes [apolipoprotein E (apoE), ABCA1, ABCG1, and sterol
      regulatory element binding protein-1c (SREBP-1c)] and a decrease in ligand
      induced apoE expression. Moreover, IL-1beta and TNF-alpha significantly reduced
      liver X receptor response element (LXRE)-driven transcription as measured by LXRE
      linked luciferase activity. However, overexpression of LXRalpha/RXRalpha only
      partially restored the cytokine-mediated reduction in LXRE-linked luciferase
      activity. Additionally, expression of the LXR coactivators peroxisome
      proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha) and steroid
      receptor coactivator-2 (SRC-2) was decreased by IL-1beta or TNF-alpha. We
      conclude that the APR suppresses the expression of both nuclear receptors
      LXRalpha/RXRalpha and several LXRalpha coactivators in kidney, which could be a
      mechanism for coordinately regulating the expression of multiple LXR target genes
      that play important roles in lipid metabolism in kidney during the APR.

PMID- 16106053
TI  - Quantification of lipid alkyl radicals trapped with nitroxyl radical via HPLC
      with postcolumn thermal decomposition.
AB  - Lipid alkyl radicals generated from polyunsaturated fatty acids via chemical or
      enzymatic H-abstraction have been a pathologically important target to quantify.
      In the present study, we established a novel method for the quantification of
      lipid alkyl radicals via nitroxyl radical spin-trapping. These labile lipid alkyl
      radicals were converted into nitroxyl radical-lipid alkyl radical adducts using 3
      carbamoyl-2,2,5,5-tetramethyl-3-pyrroline-N-oxyl (CmdeltaP) (a partition
      coefficient between octanol and water is approximately 3) as a spin-trapping
      agent. The resulting CmdeltaP-lipid alkyl radical adducts were determined by HPLC
      with postcolumn online thermal decomposition, in which the adducts were degraded
      into nitroxyl radicals by heating at 100 degrees C for 2 min. The resulting
      nitroxyl radicals were selectively and sensitively detected by electrochemical
      detection. With the present method, we, for the first time, determined the lipid
      alkyl radicals generated from linoleic acid, linolenic acid, and arachidonic acid
      via soybean lipoxygenase-1 or the radical initiator 2,2'-azobis(2,4-dimethyl
      valeronitrile).

PMID- 16106054
TI  - The continuing evolution of immunology at Washington University.

PMID- 16106052
TI  - Lack of stimulation of cholesteryl ester transfer protein by cholesterol in the
      presence of a high-fat diet.
AB  - Cholesteryl ester transfer protein (CETP) is a key protein involved in the
      reverse cholesterol transport pathway. The regulation of CETP by dietary fats is
      not clearly understood. Transgenic mice expressing human CETP under the control
      of its natural flanking region were fed low- or high-fat diets enriched in
      monounsaturated fatty acids (MUFAs) or saturated fatty acids in the presence or
      absence of cholesterol. Addition of cholesterol to the low-fat MUFA diet
      increased CETP activity and mRNA expression, whereas addition of cholesterol to
      the high-fat MUFA diet led to a decrease in CETP activity and mRNA expression. In
      SW 872 cells, oleic acid and cholesterol stimulated CETP gene expression when
      given alone. However, addition of fatty acids along with cholesterol interfered
      with the stimulatory effect of cholesterol on CETP gene regulation. Cholesterol
      mediated stimulation of CETP involves the transcription factor liver X receptor
      alpha (LXRalpha). High-fat MUFA diets inhibited the expression of LXRalpha, and
      addition of cholesterol to the high-fat MUFA diet did not rescue LXRalpha
      expression. Therefore, we present evidence for the first time that inhibition of
      LXRalpha expression by a high-fat MUFA diet leads to inhibition of CETP
      stimulation by cholesterol.

PMID- 16106055
TI  - Initiation of an autoimmune response: insights from a transgenic model of
      rheumatoid arthritis.
AB  - K/BxN mice develop an inflammatory joint disease with many features
      characteristic of rheumatoid arthritis. This model is based on a T-cell receptor
      transgene, KRN, that has been shown to recognize both the foreign antigen bovine
      RNase, and the ubiquitously expressed self antigen, glucose-6-phosphate isomerase
      (GPI). We have used this model to investigate the initial events that occur
      during the autoimmune response to GPI. We and others have identified key
      mediators in the inflammatory response: Fc receptors (FcRs) (in particular
      FcRIII), the alternative pathway of complement, neutrophils, and mast cells.
      Using micro position emission tomography, we demonstrated that anti-GPI
      Immunoglobulin G (IgG) localizes specifically to the joints where arthritis
      occurs and that this localization is dependent on mast cells, neutrophils, FcRs,
      and immune complexes. The trigger of arthritis in this model is the KRN T-cell
      inducing the production of anti-GPI Ig. By overexpressing the ligand for the KRN
      T-cells in major histocompatibility complex class II-expressing cells, we
      demonstrated that KRN T-cells were able to escape tolerance induction in the
      thymus owing to insufficient levels of antigen in the thymus antigen-presenting
      cells. This allows the KRN T-cells to exit to the periphery, where they provide
      help to anti-GPI B-cells, inducing the production of arthritogenic Ig. To
      understand the joint specificity of the disease, we followed the anti-GPI B-cell
      response that naturally arises in K/BxN mice and showed that, although the GPI
      antigen is ubiquitously expressed, the anti-GPI B-cell response is focused on the
      lymph nodes draining the affected joints. Together, these studies have given us a
      greater understanding of how an autoimmune response is initiated at the level of
      both the adaptive and innate immune systems and demonstrate the versatility of
      the K/BxN arthritis model for studying human disease.

PMID- 16106056
TI  - Function of tumor necrosis factor receptor family members on regulatory T-cells.
AB  - Effector cells play a crucial role in the immune system of higher vertebrates in
      eliminating invading pathogens and transformed cells that could cause disease or
      death of the individual. To be effective and specific, immune responses have to
      distinguish between self and nonself. Mechanisms of central and peripheral
      tolerance have evolved to control effector cells that could respond to
      autoantigens. Regulatory T-cells (Treg cells) are critical modulators of effector
      cells in the periphery that suppress autoreactive T-cells but are also involved
      in modulating immune responses against invading pathogens. Identification of
      surface markers of Treg cells and the development of in vitro systems to study
      the suppressive function of Treg cells have revealed distinct phenotypic and
      functional subsets of Treg cells. Several tumor necrosis factor receptor (TNFR)
      family members have been shown to play a role in the development, homeostasis,
      and suppressor function of Treg cells. Recent findings suggest that TNFRs and
      other cell-surface molecules of Treg cells can be explored for therapeutic
      strategies targeting autoimmune disorders, cancer, and immune responses against
      pathogens.

PMID- 16106057
TI  - T-cell stimulation and regulation: with complements from CD46.
AB  - Crosslinking of CD46 and CD3 on naive human CD4+ T-lymphocytes induces
      interleukin-10 secretion and granzyme B expression. These highly proliferative T
      regulatory type 1-like T-regulatory T-cells (Tregs) can suppress an immune
      response. We propose that this process is important in the prevention of chronic
      inflammation such as at epithelial borders and in deactivation of a successful
      immune response. Relative to the latter, once a complement-fixing polyclonal
      antibody response has been mounted, in most cases, the pathogen will be rapidly
      destroyed. At this time, the C3b/C4b-bearing immune complexes could initiate the
      deactivation arm of an immune response by shutting down immunocompetent cells
      through CD46-generated T-cells. Herein, we review this pathway for the induction
      of Tregs, focusing on a role for the complement system and especially signaling
      through CD46 on human T-cells.

PMID- 16106058
TI  - Understanding the pathogenesis of psoriasis, psoriatic arthritis, and
      autoimmunity via a fusion of molecular genetics and immunology.
AB  - The goal of my laboratory is to understand the molecular genetics basis of the
      inflammatory skin disease psoriasis and associated psoriatic arthritis. In
      performing these studies my colleagues and I have begun to identify common
      pathways leading to autoimmunity as well, because some of the defective pathways
      leading to autoimmunity are the same in different autoimmune diseases. Some of
      these pathways are involved in determining the activation status of inflammatory
      cells in the resting state. Other pathways are likely to determine target organ
      specificity and will be unique to a particular disease. Our approaches rely on
      genetic studies with cases and families to identify the causative variants, and
      then functional studies to identify the role of these variants in the
      predisposition to psoriasis and autoimmunity. The advantage of genetics
      approaches to understanding diseases such as those of the immune system is that
      one can identify novel genes and pathways that were not previously suspected as
      being involved in either the immune system or tolerance.

PMID- 16106059
TI  - Developmental relationship between hematopoietic and endothelial cells.
AB  - Blood (hematopoietic cells) and blood vessels (endothelial cells) develop from
      mesoderm via a transitional progenitor known as the hemangioblast. Flk-1, a
      receptor tyrosine kinase, and Scl, a basic helix-loop-helix transcription factor,
      are two critical molecules functioning in this process. Recent studies have shown
      that Flk-1 expressing mesoderm contributes to the circulatory system, including
      hematopoietic, endothelial, smooth muscle, skeletal muscle, and cardiac muscle
      cells. Our studies suggest that hemangioblast specification within Flk-1
      expressing mesoderm is regulated by Scl expression. Herein, we review studies
      that have utilized transgenic mouse models as well as an in vitro model of
      embryonic stem cell differentiation, both of which have greatly contributed to
      the current understanding of the cellular and molecular pathways regulating
      hemangioblast development and differentiation.

PMID- 16106060
TI  - Plasmacytoid dendritic cells: in search of their niche in immune responses.
AB  - Plasmacytoid dendritic cells (pDCs) have been associated with several names and
      functions over time, reflecting the limited availability of specific markers and
      their ability to produce large amounts of type I interferons, present antigens,
      as well as prime disparate T-cell helper responses. Yet, there is increasing
      evidence that pDCs are a distinct cell type in the innate immune system. This
      review highlights aspects in which pDCs are unique in comparison to other antigen
      presenting cells in regulating innate and adaptive immune responses.

PMID- 16106061
TI  - Humoral immunity in multiple sclerosis and its animal model, experimental
      autoimmune encephalomyelitis.
AB  - Abnormal immunoglobulin synthesis within the central nervous system is a common
      finding in patients with multiple sclerosis (MS) that is often used for
      diagnosis. However, it is not clear whether antibodies, or the B-cells and plasma
      cells that make them, are critical to the pathogenesis of MS. Here we review the
      descriptive data that suggest a role for antibody in the pathogenesis of MS. The
      results of B-cell and antibody depletion studies in the animal model for MS,
      experimental autoimmune encephalomyelitis, are summarized, as well as early data
      using a chimeric monoclonal antibody to deplete B-cells in patients with MS.

PMID- 16106062
TI  - Signals from dying cells: tolerance induction by the dendritic cell.
AB  - Uncontrolled immune responses are central to the pathogenesis of sustained viral
      infection, tumor growth, autoimmune diseases, and organ rejection. Dendritic
      cells (DCs) are critical to determining the outcome of immune responses by
      directing the function of T-cells. When DCs encounter antigen together with
      maturation signals immunity results; however, when they encounter apoptotic cells
      immune tolerance can be induced. It is thought that this is a mechanism to help
      prevent responses to self antigens because apoptotic cells can enter antigen
      processing pathways. Our interest is the mechanisms by which DCs induce tolerance
      to the antigens associated with apoptotic cells. Here, we examine evidence
      showing a pivotal role for interleukin-10 (IL-10) in regulating the response of
      DCs to apoptotic cells. We show that although tolerogenic DCs are CD11c+ and
      CD8alpha+, the important DCs reside in a subpopulation of these cells that also
      express IL-10R. Current studies are designed to isolate and characterize this
      extremely small, but potent, subpopulation of tolerance-inducing DCs.

PMID- 16106063
TI  - Applications of major histocompatibility complex class I molecules expressed as
      single chains.
AB  - Generation of CD8 T-cell responses to pathogens and tumors requires optimal
      expression of class I major histocompatibility complex/peptide complexes, which,
      in turn, is dependent on host cellular processing events and subject to
      interference by pathogens. To create a stable structure that is more immunogenic
      and resistant to immune evasion pathways, we have engineered class I molecules as
      single-chain trimers (SCTs), with flexible linkers connecting peptide, beta2m,
      and heavy chain. Herein we extend our earlier studies with SCTs to the K(b)
      ligand derived from vesicular stomatitis virus (VSV) to characterize further SCTs
      as probes of immune function as well as their potential in immunotherapy. The
      VSVp-beta2m-K(b) SCTs were remarkably stable at the cell surface, and
      immunization with DNA encoding SCTs elicited complex-specific antibody. In
      addition, SCTs were detected by cytotoxic T-lymphocytes specific for the native
      molecule, and the covalently bound peptide was highly resistant to displacement
      by exogenous peptide. SCTs can also prime CD8 T-cells in vivo that recognize the
      native molecule. Furthermore, SCTs were resistant to downregulation by the immune
      evasion protein mK3 of gamma herpesvirus 68. Moreover, owing to their
      preassembled nature, SCTs should be resistant to other immune evasion proteins
      that restrict peptide supply. Thus, SCTs possess therapeutic potential both for
      prophylactic treatment and for the treatment of ongoing infection.

PMID- 16106064
TI  - Defining and adjusting divergent host responses to viral infection.
AB  - Our laboratory focuses on the signal-transduction basis for mucosal immunity,
      inflammation, and remodeling, especially in relation to respiratory viral
      infection. Our approach aims to answer two major questions: (1) What are the
      mechanisms that control common viral infections? and (2) How can these transient
      infections cause long-term diseases, such as asthma? Our studies show that
      antiviral defense depends critically on a specialized network of mucosal
      epithelial cells and macrophages. When this network is compromised, the host is
      highly susceptible to infection, but when it is engineered to be broadly
      hyperresponsive to interferon, the host is markedly resistant to otherwise lethal
      viral infections. Similar but less effective hyperresponsiveness appears in
      asthma, suggesting that evolving attempts to improve antiviral defense may
      instead cause inflammatory disease. Indeed, in susceptible genetic backgrounds,
      respiratory viruses can also cause a hit-and-run phenomenon that is manifest by
      the development of a permanent asthmatic phenotype long after the infection has
      been cleared. This complex phenotype can be segregated into individual traits
      using pharmacologic, immunologic, and genetic strategies to achieve more precise
      definition of just how viruses can reprogram host behavior. Evidence of
      reprogramming is manifest by persistent abnormalities in epithelial cell survival
      and macrophage activation that when corrected can prevent the development of
      disease phenotypes. Our results led us to pursue the hypothesis that specific
      components of the innate immune system may manifest an aberrant antiviral
      response as a basis for chronic inflammatory diseases and that adjusting this
      response can improve short- and long-term outcomes after viral infection.

PMID- 16106065
TI  - Use of protease proteomics to discover granzyme B substrates.
AB  - A wide variety of proteases play important roles in immunity, including the
      destruction of microbes, induction of apoptosis, antigen processing, and
      regulation of the immune response. Characterization of these proteases requires
      not only an understanding of substrate specificity, but also the identification
      of specific protein substrates. Recent advances in proteomics technology have
      introduced new techniques for the study of protease function. Here, we highlight
      a proteomic approach used in our laboratory that employs two-dimensional gel
      electrophoresis coupled with mass spectrometry to identify native protease
      substrates. With this technique, we have successfully detected both known and
      novel granzyme B substrates, characterized cleavage products, and identified a
      granzyme B cleavage site. This approach may serve as an important discovery tool
      for other immunologic proteases.

PMID- 16106066
TI  - CD25+ CD4+ regulatory T-cells in cancer.
AB  - Regulatory T-cells (Treg) protect the host from autoimmune disease by suppressing
      self-reactive immune cells. As such, Treg may also block antitumor immune
      responses. Recent observations by us and others showed that the prevalence of
      Treg is increased in cancer patients, particularly in the tumor environment. Our
      studies in a mouse pancreas cancer model suggest that the tumor actively promotes
      the accrual of Treg through several mechanisms involving activation of naturally
      occurring Treg as well as conversion of non-Treg into Treg. Our studies focus on
      further defining these mechanisms with the ultimate goal of designing strategies
      that block Treg-mediated suppression in cancer patients.

PMID- 16106067
TI  - Neutrophil homeostasis: a new role for stromal cell-derived factor-1.
AB  - Neutrophils are a key component of the innate immune response and a major
      contributor to inflammation. Accordingly, their number in the blood is tightly
      controlled. Neutrophils are normally produced exclusively in the bone marrow, and
      their release into the blood is tightly regulated to maintain homeostatic levels
      in the blood. Herein, recent evidence is reviewed showing that stromal cell
      derived factor-1 (SDF-1, CXCL12) plays a key role in regulating neutrophil
      trafficking in the bone marrow. Moreover, studies are discussed showing that
      granulocyte colony-stimulating factor, primarily through regulation of SDF-1
      expression in the bone marrow, plays an essential role in maintaining neutrophil
      homeostasis in the blood.

PMID- 16106068
TI  - Molecular mechanisms of chronic rejection following transplantation.
AB  - Although significant advances have been made in the field of organ
      transplantation, chronic rejection remains a major limiting factor for prolonged
      graft survival. The long-term survival and function of transplanted lungs are
      limited by the development of bronchiolitis obliterans syndrome (BOS). The 10-yr
      lung graft survival rate is only 18.6%. Aside from results of several clinical
      studies that strongly support the concept that BOS results from alloimmune
      mediated injury, little is known regarding specific immune effectors or target
      molecules involved in the pathogenesis of BOS. Studies from our laboratory have
      provided evidence for the seminal role of CD4+ T-cells in the pathogenesis of
      obliterative airway disease (OAD) seen in BOS. Prior to any clinically detectable
      lesions, there is indirect antigen presentation of mismatched major
      histocompatibility complex (MHC) class I antigen and production of antibodies to
      these MHC antigens. Both MHC and minor histocompatibility antigen disparities can
      result in the development of OAD in animal models and preliminary results
      strongly suggest that peptide vaccination strategies may prevent OAD following
      heterotopic tracheal transplants. Using a newly developed orthotopic tracheal
      transplant model, we have obtained evidence for an important and probably
      exclusive role for airway epithelial cell injury as a primary mechanism for the
      immunopathogenesis of the development of OAD.

PMID- 16106069
TI  - Complement regulation during pregnancy.
AB  - Complement has an important role in innate immunity and inflammation. Complement
      also has the capacity to attack self tissues. Cells are protected from the
      deleterious effects of complement. The Crry protein belongs to a family of
      molecules that regulates complement activation, protecting tissues from
      complement-mediated damage. To investigate the role of these molecules in vivo,
      Crry-/- mice were generated. Crry-/- mice did not survive pregnancy owing to
      abnormal complement deposition in the placenta through the alternative pathway.
      Tissue damage related to C5 (production of C5a and C5b-9) was not required.
      Removal of inflammatory cells did not affect the phenotype. This suggests new
      noninflammatory mechanisms of pregnancy failure that are dependent solely on C3.
      The major abnormality was a failure of blood vessel formation in the placenta,
      revealing an unsuspected C3 effect in the vascular development of this organ.

PMID- 16106070
TI  - Fate vs choice: the immune system reloaded.
AB  - Development can occur by either instructive or stochastic processes. My
      colleagues and I have studied the contributions of these processes to
      differentiation of naive CD4+ T-cells to either a Th1 or Th2 phenotype. Our
      initial discovery that pathogens in our in vitro priming system led to the
      development of Th1 cells through the action of interleukin-12 was important
      evidence of a link between innate and adaptive immunity. Subsequent studies in
      our laboratory revealed an important role for GATA-3 autoactivation in Th2
      development. Other interesting projects that have emerged as a result of our Th
      cell differentiation studies include understanding the role of the inhibitory
      immunoreceptor B- and T-lymphocyte attenuator in the immune response, as well as
      the role of the transcription factor ERM in both T-cells and spermatogenesis. We
      currently maintain our interests in the Th differentiation field by trying to
      understand the role of type 1 interferons in Th1 development and the role of
      alternate promoters for the GATA-3 gene, among other things, but are also
      actively embarking on studies related to the choice between divergent cell types
      during embryonic stem cell differentiation.

PMID- 16106071
TI  - Target identification and validation in systemic autoimmunity.
AB  - In systemic, humoral autoimmune diseases such as systemic lupus erythematosus, a
      pathogenic hyperactivation of T- and B-lymphocytes results in the elaboration of
      high-titer, high-affinity autoantibodies that mediate end organ damage. Although
      several T-dependent and -independent cell-surface molecules and cytokines, such
      as CD154 and the interferons, have been proposed to play key roles in disease,
      they have remained insufficient to explain fully the pathophysiology of these
      syndromes and have so far failed to yield premium therapeutic targets. Recent
      genome-based approaches to autoimmunity, however, have revealed novel pathogenic
      targets, including genes that negatively regulate T- and/or B-cell effector
      differentiation, as well as genes that specifically regulate T-cell-B-cell
      collaboration. It is hoped that continued investigation of such pathogenic
      targets will yield novel and specific therapeutic agents for the treatment of
      human autoimmune conditions.

PMID- 16106072
TI  - Neutrophil-derived serine proteases in immune complex-mediated diseases.
AB  - Neutrophil-derived serine proteases play an important role in fighting
      infections. However, emerging data suggest that these proteases also regulate
      noninfectious inflammatory responses. Loss-of-function mutations in serine
      proteases have provided critical insights into the significance of these serine
      proteases in initiating and amplifying immune complex-mediated diseases.

PMID- 16106073
TI  - Pathogenesis and treatment of human T-cell leukemia virus infection.
AB  - The pathogenesis of human T-cell leukemia virus (HTLV)-induced adult T-cell
      leukemia-lymphoma (ATLL) was explored using an infectious molecular viral clone
      and a transgenic mouse model. Activation of nuclear factor-kappaB by the HTLV
      transcriptional transactivator protein Tax was found to be important for
      lymphocyte immortalization and tumorigenesis. Interferon-gamma regulates tumor
      development owing primarily to angiostatic effects. Translational clinical
      studies of chemotherapy, interferon-alpha, and nucleoside reverse transcriptase
      inhibitors have also assisted in identifying the pathogenic features of ATLL.

PMID- 16106074
TI  - Interaction between the immune and central nervous systems.
AB  - Much of the understanding of tolerance has focused on the requirements for
      antigen-specific lymphocyte activation and function. However, there is increasing
      evidence for anatomic regulation of effector access to self antigens. Recently, a
      number of studies have provided evidence for tissue-specific "addressins" in
      chemokine/chemokine receptor pairs. The central nervous system (CNS) provides
      special anatomic barriers to the movement of cells from the vascular compartment
      to the parenchyma. Herein I raise the possibility that antigen, perhaps through
      specialized antigen-presenting cells, may play a role in regulating access of
      activated lymphocytes into the CNS parenchyma. The results suggest that a
      reexamination of the widely held dogma that all activated lymphocytes have access
      to the CNS parenchyma is necessary to understand the relationship between the
      immune and central nervous systems.

PMID- 16106075
TI  - Interferon-gamma and cancer immunoediting.
AB  - Over the last 12 yr, we have shown that interferon-gamma and lymphocytes
      collaborate to regulate tumor development in mice. Specifically, we found that
      the immune system not only prevents the growth of primary (carcinogen-induced and
      spontaneous) and transplanted tumors but also sculpts the immunogenicity of
      tumors that form. These observations led us to refine the old and controversial
      "cancer immunosurveillance" hypothesis of Burnet and Thomas into one that we
      termed cancer immunoediting that better emphasizes the paradoxical host
      protective and tumor-sculpting roles of immunity on developing tumors. Our
      current work focuses on defining the molecular mechanisms that underlie cancer
      immunoediting and exploring the implications of this process for cancer
      immunotherapy.

PMID- 16106076
TI  - T-cell activation and immunologic synapse.
AB  - The focus of my laboratory is in three areas. The first area is our long-standing
      interest in the mechanics of T-cell activation. In addition to our interest in
      protein phosphorylation mediated by T-cell receptor engagement, we have been
      interested in defining the function of the immunologic synapse. The second area
      of focus is on the pathogenesis of glomerular disease. Here we are interested in
      the function of the podocyte and trying to understand how genetic deficiency of
      CD2AP in podocytes leads to kidney failure. The third area is the effect of
      modifiers of protein kinase cascades. Here we are focused on scaffold proteins,
      namely KSR and its role in controlling the activation of mitogen-activated
      protein kinase.

PMID- 16106077
TI  - Lymphocyte antigen receptor gene assembly: multiple layers of regulation.
AB  - Lymphocyte antigen receptor genes are assembled through the cutting and joining
      of segments of DNA in developing lymphocytes. The basic features of the
      biochemical steps of this assembly process, referred to as the V(D)J
      recombination, are similar for the assembly of all lymphocyte antigen receptor
      genes, yet this assembly is precisely regulated in several important contexts
      during lymphocyte development. It has long been appreciated that this occurs
      through modulation of accessibility of antigen receptor loci to the enzymatic
      complex that assembles antigen receptor genes. However, recent studies have
      suggested that some regulatory constraints may be enforced at the level of the
      V(D)J recombination reaction itself. This review focuses on recent advances in
      the understanding of the regulation of antigen receptor gene assembly, with
      particular attention paid to the assembly of T-cell receptor beta-chain genes
      during T-cell development.

PMID- 16106078
TI  - The Vav family: at the crossroads of signaling pathways.
AB  - The Vav family of Rho-guanine nucleotide exchange factors (GEFs) is thought to
      control a diverse array of signaling pathways emanating from antigen receptors in
      lymphocytes, although the exact mechanism by which Vav exerts its function is
      only beginning to emerge. Vav proteins are modular and contain the Dbl-homology
      domain, typical of all known Rho-GEFs, in addition to several other structural
      domains characteristic of proteins involved in signal transduction. Recently, our
      laboratory generated mice congenitally lacking all three Vav isoforms, providing
      genetic evidence that the Vav family is critical and nonredundant in T- and B
      lymphocyte development and function and is essential in the formation of the
      adaptive immune system. These experiments also demonstrated that Vav proteins are
      indispensable for both T-cell receptor- and B-cell receptor-induced Ca++ fluxes.
      However, detailed analyses of Vav-deficient mice revealed unexpected complexity
      of Vav involvement in cellular activation. Notably, we observed lineage-specific
      Vav regulation of mitogen-activated protein kinase signaling, in which Vav was
      required in T-cells, but not in B-cells. Moreover, the three Vav proteins appear
      to function specifically in distinct signaling pathways emanating from activating
      receptors of natural killer cells that trigger natural cytotoxicity.

PMID- 16106079
TI  - Antigen presentation: lysoyme, autoimmune diabetes, and Listeria--what do they
      have in common?
AB  - We discuss three areas of antigen presentation and macrophage biology being
      investigated in the laboratory. Using hen egg-white lysozyme as a protein
      antigen, all the segments of the molecules selected by the class II
      histocompatibility molecule I-A(k) were identified and characterized. The display
      of each family of peptides was explained biochemically and quantitated.
      Conformational isomers of a peptide-major histocompatibility complex (MHC)
      complex were identified. The relationship between the amounts of peptide-MHC
      displayed by the antigen-presenting cells and two biologic responses, central
      thymic selection and T-cell responses after immunization in adjuvant, were
      examined. The class II MHC molecule of the nonobese diabetic I-Ag7 is being
      examined for its properties of peptide selection. The objective is to identify
      the diabetogenic peptides, as well as the repertoire of protein antigens from
      beta-cells that trigger autoantibodies. The I-Ag7 molecule selects peptides that
      show very distinctive sequence motifs: one or more acidic residues at the carboxy
      terminus that interact at the P9 pocket of the binding groove. Finally, the
      investigations in listeriosis examined the early events in immune induction. More
      important, we found that Listeria causes marked apoptosis of lymphocytes around
      infective foci resulting from the apoptogenic properties of the pore-forming
      molecule Listeriolysin O.

PMID- 16106080
TI  - Immune regulation of viral infection and vice versa.
AB  - In our laboratory we study the mechanisms by which the immune system controls
      viral infection and by which viruses evade immune control. To study issues at
      this interface between virology and immunology, we work from the hypothesis that
      viruses manipulate the immune response as the immune response attempts to
      eradicate the virus. Analysis of these issues is key to understanding acute and
      chronic diseases caused by viruses. Two concepts drive our approach: (1) the
      simultaneous analysis of immune and viral mechanisms allows novel insights, and
      (2) genetic tests in vivo are necessary to establish mechanisms.

PMID- 16106082
TI  - Making the best of what we have: a plea for wider use of anthelmintics.

PMID- 16106081
TI  - Natural killer cell immune responses.
AB  - Natural killer (NK) cells play a vital role in innate immune responses to
      infection; they express activation receptors that recognize virus-infected cells.
      Highly related to receptors recognizing tumor cells, the activation receptors
      trigger cytotoxicity and cytokine production. NK cells also express inhibitory
      receptors for major histocompatibility complex (MHC) class I molecules that block
      the action of the activation receptors. Although many ligands for NK cell
      receptors have MHC class I folds, recent studies also indicate ligands resembling
      the NK cell receptors themselves. A combination of immunologic, genetic,
      biophysical, and in vivo approaches is being employed to understand fully how
      these receptors contribute to NK cell activities in innate immunity to pathogens
      and tumors.

PMID- 16106083
TI  - Rabies: an ancient disease that still prevails.

PMID- 16106084
TI  - TT viruses: how much do we know?

PMID- 16106085
TI  - Chromosomal abnormalities & male infertility.

PMID- 16106086
TI  - Nephrotic syndrome in children.
AB  - Nephrotic syndrome is an important chronic disease in children, characterized by
      minimal change disease in the majority. Research on pathogenesis has emphasized
      the importance of T lymphocyte dysregulation and vascular permeability factors
      that might alter podocyte function and permselectivity. While mutations in genes
      that encode important podocyte proteins have also been identified, a hypothesis
      unifying available evidence on pathogenesis is yet to be proposed. Patients with
      nephrotic syndrome are at risk for life threatening infections and thromboembolic
      episodes. Long-term effects of persistent hyperlipidaemia and prolonged steroid
      therapy are increasingly recognized. Remission of proteinuria following
      corticosteroid therapy has greater prognostic value, in relation to long-term
      outcome, than the precise renal histology. Prospective studies show that
      prolonged duration of therapy for the initial episode results in sustained
      remission and reduced frequency of relapses. Treatment with levamisole,
      cyclophosphamide, cyclosporine and mycophenolate mofetil is beneficial in a
      variable proportion of patients with frequent relapses or steroid dependence. The
      management of steroid-resistant nephrotic syndrome is difficult; most patients
      failing to achieve remission show progressive renal damage. Calcineurin
      inhibitors (cyclosporine, tacrolimus) are capable of inducing remission in a
      significant proportion of patients, but at risk of nephrotoxicity. Reduction of
      proteinuria is also possible, in children, using angiotensin converting enzyme
      inhibitors and/or angiotensin receptor blockers. Prospective trials are necessary
      to identify effective and safe therapies for patients with frequent relapses,
      steroid dependence and resistance.

PMID- 16106087
TI  - Presence of TT virus infection in chronic hepatitis patients from a hospital in
      New Delhi, India.
AB  - BACKGROUND & OBJECTIVE: The recent discovery of a novel parenterally transmitted,
      unenveloped, single-stranded DNA virus called TT virus (TTV) in chronic hepatitis
      patients with unclear pathogenesis throughout the world led us to investigate,
      its presence in chronic hepatitis patients attending a hospital in New Delhi,
      India, and to evaluate its role in liver disease. METHODS: TT virus DNA was
      investigated in serum samples of 70 patients with various types of chronic
      hepatitis, and 100 healthy subjects from New Delhi, India by nested PCR using the
      primers that belonged to UTR (A) region of the genome. RESULTS: TTV DNA was
      detected in 6 of 23 patients (26%) with type B chronic hepatitis, 3 of 20
      patients (15%) with type C chronic hepatitis, and 12 of 100 subjects (12%) from
      healthy control group with normal liver function profile tests. None of the 27
      non-B, non-C chronic hepatitis patients had TTV DNA positivity. The prevalence of
      TTV was significantly higher in type-B chronic hepatitis patients as compared to
      normal subjects (P< 0.05) but comparable to type C chronic hepatitis patients.
      The clinical course and biochemical profiles of type B, or type C chronic
      hepatitis patients co-infected with TTV did not differ significantly from those
      without TTV infection. INTERPRETATION & CONCLUSION: Interestingly, in chronic
      hepatitis patients, TTV was always associated with either hepatitis B or C virus
      indicating a likely parenteral route of transmission. All TTV-positive subjects
      in healthy control group showed normal clinical and biochemical profiles. Thus,
      the presence of TTV infection is unlikely to influence the course of chronic
      hepatitis related to hepatitis B virus (HBV) or hepatitis C virus (HCV) or cause
      liver diseases in healthy subjects.

PMID- 16106088
TI  - Chromosomal studies in infertile men with oligozoospermia & non-obstructive
      azoospermia.
AB  - BACKGROUND & OBJECTIVE: Chromosomal anomalies have been postulated to be as one
      of the principal genetic factors in male infertility. Cytogenetic evaluation of
      men with severely compromised semen parameters reveals an increased incidence of
      chromosomal aberrations when compared with the normal population. The objective
      of this study was to determine the chromosomal constitution and sperm
      characteristics among Indian males with severe male factor infertility. METHODS:
      In this prospective study we investigated 88 infertile men (42 men with
      azoospermia and 46 men with sperm count <5 x 10(6) million/ml) prior to
      intracytoplasmic sperm injection (ICSI) treatment. Karyoptying was performed on
      peripheral blood lymphocytes according to standard methods. Polymerase chain
      reaction (PCR) was performed to screen the microdeletions in the AZF region of
      the Y chromosome. RESULTS: Constitutional chromosome abnormalities were
      identified in 14.3 per cent of azoospermic and 6.5 per cent of oligozoospermic
      men, with an overall rate of 10.2 per cent. Chromosomal abnormalities included
      gonosomal aberrations in 5 cases. Robertsonian translocation in one, trisomy 7
      mosaicism in one case, deletion in chromosome 16 in one, and a marker chromosome
      in one case. Chromosome variants were observed in 33 (37.5%) subjects. Yqh- was
      the most frequent variant in sex chromosomes and increased length in
      heterochromatin and satellites were observed in autosomal chromosomes.
      INTERPRETATION & CONCLUSION: The high rate of chromosomal anomalies among
      infertile men strongly suggests the need for routine cytogenetic analysis prior
      to employment of assisted reproduction techniques. In addition, meticulous follow
      up of babies born after ICSI, especially male offsprings, is necessary.

PMID- 16106089
TI  - Undernutrition & childhood morbidities among tribal preschool children.
AB  - BACKGROUND & OBJECTIVE: Undernutrition and various morbidities go hand in hand,
      particularly in children. Nutritional status is a sensitive indicator of
      community health and nutrition. The present study is an attempt to assess the
      nutritional status of pre-school children of Gond tribal community in Madhya
      Pradesh. METHODS: The study was a community-based, cross- sectional survey
      carried out in tribal preschool children. Anthropometric measurements were taken.
      Various indices of nutritional status were expressed in standard deviation units
      (z scores) from the reference median. The children were examined for nutritional
      deficiencies and other morbidities. The haemoglobin concentration was measured
      and the children were classified into various grades of nutritional anaemias.
      Data on socio-cultural and hygienic practices were also collected. RESULTS: More
      than 60 per cent children were underweight. Micronutrient deficiency disorders
      such as anaemia and vitamin A deficiency were common among them. Unhygienic
      personal habits and adverse cultural practices relating to child rearing, breast
      feeding and weaning were also prevalent among them. INTERPRETATION & CONCLUSION:
      The findings of the present study revealed the widespread prevalence of
      undernutrition among pre-school tribal children and highlight a need for an
      integrated approach towards improving the child health as well as nutritional
      status in this area.

PMID- 16106090
TI  - Comparison of disc diffusion results with minimum inhibitory concentration (MIC)
      values for antimicrobial susceptibility testing of Neisseria gonorrhoeae.
AB  - BACKGROUND & OBJECTIVE: objectives: As antimicrobial susceptibility testing of
      Neisseria gonorrhoeae provides guidance for appropriate treatment, there is a
      need for simple, reliable and cost-effective method for susceptibility testing.
      The present study was aimed to compare the results of two methods of
      susceptibility testing, minimum inhibitory concentration (MIC) values by E test
      with disc diffusion results by Australian Gonococcal Surveillance Programme
      (AGSP) method in N. gonorrhoeae isolates. METHODS: Susceptibility testing for
      ciprofloxacin, penicillin and ceftriaxone using AGSP method was carried out for
      301 confirmed consecutive isolates of N. gonorrhoeae. MIC of ciprofloxacin,
      penicillin and ceftriaxone was determined by E test in 301, 198 and 128 isolates
      respectively. The results of the two methods were compared by using Kappa
      statistics. RESULTS: Moderate levels of agreement for ciprofloxacin (kappa=0.44)
      and penicillin (kappa=0.54) were observed between the two methods. For
      ceftriaxone, 96.1 and 0.8 per cent isolates were found to be susceptible and less
      sensitive respectively by both the methods and per cent agreement between the two
      methods was 96.9 per cent. INTERPRETATION & CONCLUSION: Both the methods were
      easy to perform and gave reproducible results. However, disc diffusion method was
      cost-effective and more feasible in routine diagnostic laboratories in developing
      countries like India.

PMID- 16106091
TI  - Clostridium perfringens type A & antibiotic associated diarrhoea.
AB  - BACKGROUND & OBJECTIVE: Clostridium perfringens type A (CPA) isolates produce
      lethal necrotizing antigens and the heat resistant forms of the organism are
      associated with pathogenic outcome in humans. CPA has also been implicated in
      antibiotic associated diarrhoea (AAD). We therefore undertook this study to
      investigate the presence of CPA in stool samples of patients with AAD in a
      tertiary care setting in north India. METHODS: A total of 285 stool samples
      obtained from patients suspected for Clostridium difficile aetiology were
      examined for the presence of CPA antigens. Four sets of reagents (CP-I, CP-II, CP
      III and CP- IV) comprising latex beads coated with polyvalent immune sera to 17
      serotypes of heat resistant CPA were used in the study. Agglutination reaction
      was carried out using the reagents with the stool supernatants. RESULTS: Of the
      285 stool samples tested, 25 (8.77%) were positive for at least one or more of
      the four polyvalent sets. Briefly, 48 per cent were positive for all the four
      sets, 12 per cent for 3 sets, 28 per cent for 2 sets and 12 per cent for only one
      set, indicating the prevalence of multiple serotypes of CPA. Twenty three (92%)
      of the 25 positive samples came from patients who were on antibiotics. C.
      difficile toxin was also present in 9 of 25 (36%) of the samples positive for CPA
      antigens. INTERPRETATION & CONCLUSION: In our setting, CPA could thus be
      associated with AAD either by itself or in synergy with C. difficile infection.
      Assessment of true burden of CPA associated AAD would be required to take
      appropriate steps for its control in our country.

PMID- 16106092
TI  - Laboratory evaluation of fipronil against Periplaneta americana & Blattella
      germanica.
AB  - BACKGROUND & OBJECTIVE: In cockroach control, bait formulations are extensively
      used. Fipronil is one of the broad spectrum insecticides from phenyl pyrazole
      family available in bait formulation. The compound has been tested under field
      conditions. However, information on its effectiveness on different surfaces and
      at various density levels is not known. Therefore, the efficacy of a new
      formulation of fipronil 0.03 per cent (Goliath gel) was tested under laboratory
      conditions. METHODS: The bait formulation was tested against Periplaneta
      americana at the dosages of 0.025, 0.05, 0.1, 0.15 and 0.2 g/m(2), and Blatella
      germanica at 0.025, 0.05, 0.075, 0.1 and 0.125 g/m(2) on wood, cement, mud and
      thatch surface with three density levels of cockroaches viz., 5, 10 and 20
      numbers/m(2). Mortality after 24 h of exposure was observed daily for five days.
      RESULTS: Rate of mortality varied between 16.0 and 96.0 per cent in P. americana
      and 51.0 and 100.0 per cent in B. germanica on different surfaces tested. The
      mortality rate of P. americana increased line rarly from the dosage 0.025g to
      0.15 g/m(2) and at 0.2 g/m(2), it was independent. The LD(80) values of the gel
      against P. americana at high density were 0.208, 0.246, 0.361 and 0.466 g/m(2) on
      wood, cement, mud and thatch surfaces, whereas against B. germanica the values
      were 0.079, 0.081, 0.089 and 0.055 g/m(2) respectively, indicating a
      significantly (P<0.001) higher efficacy of Goliath gel against B. germanica than
      P. americana. The results of fitting logistic regression model to the observed
      percentage mortality with log dose and cockroach density as explanatory variables
      satisfactorily described the observations at all densities on each surface. The
      pattern of response to increasing dosages was similar for all the three density
      levels on each of the surfaces in P. americana and B. germanica. INTERPRETATION &
      CONCLUSION: The effectiveness assessed against P. americana and B. germanica
      using logistic regression model suggested that the gel when applied at the
      appropriate dosages on wood, cement, mud and thatch surfaces could cause >80 per
      cent mortality of these species in dwellings having these types of surfaces.

PMID- 16106093
TI  - Epidemiological study of child & adolescent psychiatric disorders in urban &
      rural areas of Bangalore, India.
AB  - BACKGROUND & OBJECTIVE: There are limited data on child mental health needs in
      our country. Therefore, an epidemiological study to determine the prevalence
      rates of child and adolescent psychiatric disorders was initiated as a two-centre
      (Bangalore and Lucknow) study by the Indian Council of Medical Research. It also
      aimed to study the psychosocial correlates of the psychiatric disorders. We
      present here the findings of Bangalore Centre. METHODS: In Bangalore, 2064
      children aged 0-16 yr, were selected by stratified random sampling from urban
      middle-class, urban slum and rural areas. The screening stage was followed by a
      detailed evaluation stage. The ICD-10 DCR criteria were used to reach a penta
      axial diagnosis. RESULTS: The results indicated a prevalence rate of 12.5 per
      cent among children aged 0-16 yr. There were no significant differences among
      prevalence rates in urban middle class, slum and rural areas. The psychiatric
      morbidity among 0-3 yr old children was 13.8 per cent with the most common
      diagnoses being breath holding spells, pica, behaviour disorder NOS, expressive
      language disorder and mental retardation. The prevalence rate in the 4-16 yr old
      children was 12.0 per cent. Enuresis, specific phobia, hyperkinetic disorders,
      stuttering and oppositional defiant disorder were the most frequent diagnoses.
      When impairment associated with the disorder was assessed, significant disability
      was found in 5.3 per cent of the 4-16 yr group. Assessment of felt treatment
      needs indicated that only 37.5 per cent of the families perceived that their
      children had any problem. Physical abuse and parental mental disorder were
      significantly associated with psychiatric disorders. INTERPRETATION & CONCLUSION:
      Prevalence rates of psychiatric morbidity in 0-16 yr old children in India were
      found to be lower than Western figures. Middle class urban areas had highest and
      urban slum areas had lowest prevalence rates. The implications for clinical
      training, practice and policy initiatives are discussed.

PMID- 16106094
TI  - Synergistic antimicrobial activity of tea & antibiotics.
AB  - Tea leaves are known for its antibacterial activity against many microorganisms.
      In this study we attempted to describe the synergistic antimicrobial activity of
      tea and antibiotics against enteropathogens. Antimicrobial activity of boiled
      water tea extract and organic solvent extract were studied against Salmonella
      typhimurium 1402/84, S. typhi, S. typhi Ty2a, Shigella dysenteriae, Yersinia
      enterocolitica C770, and Escherichia coli (EPEC P2 1265) determining minimum
      inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and
      death rate kinetics at MBC of tea extract in presence of subinhibitory
      concentration of antibiotic. Both green tea or black tea extracts effectively
      inhibited the growth of S. typhimurium 1402/84, S. typhi, S. typhi Ty2a, S.
      dysenteriae, Y. enterocolitica C770, and E.coli (EPEC P2 1265). However, the
      growth inhibitory concentration of tea extract was lower for green tea as
      compared to black tea extract. Antimicrobial activity of green tea tea methanol:
      water extract tea was better as compared to boiled water tea extract of green
      tea. Based on death rate kinetics results, S.typhi Ty2a appeared to be highly
      sensitive and Y. enterocolitica C770 the most resistant. Chloramphenicol and tea
      extract in combination inhibited the growth of S.dysenteriae at 2.5 microg/ml
      chloramphenicol (MIC 5 microg/ml) and 5.094 mg/ml black tea extract (MIC 9.089
      mg/ml). Tea extract showed synergistic activity with chloramphenicol and other
      antibiotics like gentamycin, methicillin and nalidixic acid against test strains.

PMID- 16106095
TI  - Retrieving Indian records from Medline database.

PMID- 16106097
TI  - On the role of sIL-2R measurements in rheumatoid arthritis and cancers.
AB  - A soluble IL-2 receptor (sIL-2R) is a circulating form of a membrane receptor
      localized on lymphoid and some cancer cells. The biological function of sIL-2R
      has not been completely understood. Substantially, it seems to reflect T
      lymphocyte activation in diseases of different pathology. Moreover, the soluble
      receptor has been considered, at least in part, responsible for unsuccessful
      immunotherapy with IL-2 in cancers. Several lines of evidence indicate sIL-2R
      measurements to be useful in determining disease progress and prognosis. This
      review summarizes current knowledge on the sIL-2R behavior in RA and solid
      cancers of varied etiology.

PMID- 16106098
TI  - Release of IL-1beta via IL-1beta-converting enzyme in a skin dendritic cell line
      exposed to 2,4-dinitrofluorobenzene.
AB  - We used a mouse fetal skin dendritic cell line (FSDC) to study the effect of the
      strong allergen 2,4-dinitrofluorobenzene (DNFB) on interleukin (IL)-1beta release
      and IL-1beta receptor immunoreactivity. Stimulation with DNFB (30 minutes)
      increased IL-1 release without changing the mRNA levels of the protein.
      Furthermore, DNFB increased transiently the interleukin-1beta-converting enzyme
      (ICE) activity, as measured with its fluorogenic substrate Z-Tyr-Val-Ala-Asp-AFC.
      The ICE inhibitor Z-YVAD-FMK prevented the release of IL-1beta evoked by DNFB.
      Incubation of the cells with DNFB (30 minutes) strongly increased IL-1beta
      receptor immunoreactivity. The rapid effect of DNFB on the release of mature IL
      1beta, without inducing an increase of IL-1beta mRNA in FSDC, suggests a
      posttranslational modification of pro-IL-1beta by ICE activity.

PMID- 16106099
TI  - Lipid peroxides and antioxidant enzymes in cisplatin-induced chronic
      nephrotoxicity in rats.
AB  - Cisplatin (CDDP), an anticancer drug, induces remarkable toxicity in the kidneys
      of animals and humans and it has been well documented that reactive oxygen
      species and the renal antioxidant system are strongly involved in acute renal
      damage induced by CDDP. The aim of the present study was to investigate whether
      or not the renal antioxidant system plays also an important role in chronic renal
      damage induced by repeated doses of CDDP (1 mg/kg intraperitoneally twice weekly
      during 10 weeks in rats). In order to elucidate it, serum creatinine and urea
      levels, renal glutathione and thiobarbituric acid-reactive substances (TBARS)
      content, as well as renal superoxide dismutase and glutathione peroxidase
      activities were measured in the kidney homogenates of chronically CDDP-treated
      rats and additionally histological studies were performed in the rat kidneys. The
      chronic treatment with CDDP induced a significant increase in creatinine and urea
      levels in serum, but the other parameters mentioned above were not significantly
      modified as compared to the values in nontreated rats. Taking into account these
      results, we conclude that chronic CDDP administration induces also severe
      nephrotoxicity, in contrast to CDDP acute application, without any significant
      modification in the activity of relevant antioxidant enzymes such as superoxide
      dismutase and glutathione peroxidase, renal glutathione and lipid peroxides, by
      which the role of the antioxidant system in chronic nephrotoxicity induced by
      CDDP in rats is uncertain.

PMID- 16106100
TI  - Correlation of endostatin and tissue inhibitor of metalloproteinases 2 (TIMP2)
      serum levels with cardiovascular involvement in systemic sclerosis patients.
AB  - Fibrosis of oesophagus, lungs, heart, and kidney in the course of systemic
      sclerosis (SSc) may lead to dysfunction of the above organs or even patients
      death. Recent studies point out the role of angiogenesis and fibrosis
      disturbances in the pathogenesis of SSc. Heart fibrosis is one of the most
      important prognostic factors in SSc patients. So, the aim of our study was to
      examine cardiovascular dysfunction in SSc patients and its correlation with serum
      levels of vascular endothelial growth factor (VEGF), endostatin, and tissue
      inhibitor of metalloproteinase 2 (TIMP2). The study group comprised 34 patients
      (19 with limited scleroderma (lSSc) and 15 with diffuse scleroderma (dSSc)). The
      control group consisted of 20 healthy persons, age and sex matched. Internal
      organ involvement was assessed on the basis of specialist procedures. Serum VEGF,
      endostatin, and TIMP2 levels were evaluated by ELISA. We found cardiovascular
      changes in 15 patients with SSc (8 with lSSc and 7 with dSSc). The observed
      symptoms were of different characters and also coexisted with each other. Higher
      endostatin serum levels in all systemic sclerosis patients in comparison to the
      control group were demonstrated (P < .05). Also higher serum levels of endostatin
      and TIMP2 were observed in patients with cardiovascular changes in comparison to
      the patients without such changes (P < .05). The obtained results support the
      notion that angiogenesis and fibrosis disturbances may play an important role in
      SSc. Evaluation of endostatin and TIMP2 serum levels seems to be one of the
      noninvasive, helpful examinations of heart involvement in the course of systemic
      sclerosis.

PMID- 16106101
TI  - Suppression of matrix metalloproteinase production in nasal fibroblasts by
      tranilast, an antiallergic agent, in vitro.
AB  - Allergic rhinitis is an inflammatory disease characterized by nasal wall
      remodeling with intense infiltration of eosinophils and mast cells/basophils.
      Matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are the major proteolytic
      enzymes that induce airway remodeling. These enzymes are also important in the
      migration of inflammatory cells through basement membrane components. We
      evaluated whether tranilast (TR) could inhibit MMP production from nasal
      fibroblasts in response to tumor necrosis factor-alpha (TNF-alpha) stimulation in
      vitro. Nasal fibroblasts (NF) were established from nasal polyp tissues taken
      from patients with allergic rhinitis. NF (2 x 10(5) cells/mL) were stimulated
      with TNF-alpha in the presence of various concentrations of TR. After 24 hours,
      the culture supernatants were obtained and assayed for MMP-2, MMP-9, TIMP-1, and
      TIMP-2 levels by ELISA. The influence of TR on mRNA expression of MMPs and TIMPs
      in cells cultured for 12 hours was also evaluated by RT-PCR. TR at more than 5 x
      10(-5) M inhibited the production of MMP-2 and MMP-9 from NF in response to TNF
      alpha stimulation, whereas TIMP-1 and TIMP-2 production was scarcely affected. TR
      also inhibited MMP mRNA expression in NF after TNF-alpha stimulation. The present
      data suggest that the attenuating effect of TR on MMP-2 and MMP-9 production from
      NF induced by inflammatory stimulation may underlie the therapeutic mode of
      action of the agent in patients with allergic diseases, including allergic
      rhinitis.

PMID- 16106102
TI  - Inflammatory process of CD8+ CD28- T cells in induced sputum from asthmatic
      patients.
AB  - Previously unreported CD8(+) CD28(-) and CD8(+) CD28(+) T-cell subsets occur in
      healthy individuals and expand in patients suffering from autoimmune disease.
      Here we studied, for the first time, the expression of CD8(+) CD28(+) , CD8(+)
      CD28(-) , and CD8(+) CD56(+) subpopulations in induced sputum from asthmatics.
      Using sputum samples, purified CD8(+) T cells were stained for surface antigen
      CD28, CD56, FITC-conjugated anti-perforin, and anti-IFN-gamma. Cytotoxic activity
      was evaluated in a chromium releasing test. Induced sputum CD8(+) CD28(-) T cells
      were found to be more expanded and expressed low levels of IFN-gamma in severe
      asthmatics than mild asthma and age-matched healthy controls. The predominance of
      CD8(+) CD28(-) T cells can be in part explained by the expansion of CD8(+)
      CD56(+). CD8(+) CD28(-) T cells from severe asthmatics produced high
      intracytoplasmic perforin and exerted a potent cytotoxic activity. Considering
      their phenotyping and functional properties, the CD8(+) CD28(-) T-cell subset may
      constitute an intermediate phenotype in the process of CD8(+) T-cell
      differentiation of effector-type cells in severe asthmatics. Functional studies
      showed that CD8(+) CD28(-) T cells had cytotoxic function.

PMID- 16106103
TI  - Domestic exposure to fungi and total serum IgE levels in asthmatic children.
AB  - We measured the number of airborne, viable fungi and house dust mite (HDM)
      allergen levels in the homes of a group of asthmatic children. Blood samples were
      drawn and the amounts of total and specific serum IgE were determined. The
      association between the number of fungal colonies, dust mite allergen exposure,
      and specific and total IgE was evaluated. The number of viable airborne fungi was
      high (20,543 CFU/m(3)) in those investigated houses. Der p1 concentrations on
      child's mattress exceeding 2 microg/g were found in 78.6% of the houses. A
      quantitative dose-response relationship was demonstrated between the exposure to
      viable, airborne molds and the amount of total IgE (r = 0.4399 and P = .0249) and
      the level was further increased in children with coexposure to viable fungi and
      HDM.

PMID- 16106104
TI  - Serum proinflammatory mediators at different periods of therapy in patients with
      multiple myeloma.
AB  - Multiple myeloma (MM) is a malignant disease characterized by the clonal
      proliferation of plasma cells within the bone marrow. Several cytokines have been
      demonstrated to be involved in the control of growth, progression, and
      dissemination of MM. We determined serum levels of interleukin-1beta (IL-1beta),
      soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), interleukin-8 (IL
      8), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) in 14
      newly diagnosed MM patients. The median age of the patients was 63.4 +/- 10.8
      years and all of the patients were stage III (classified according to the Durie
      Salmon classification). The same parameters were measured in 15 healthy controls.
      In addition, we also examined the effects of vincristine-adriamycin-dexamethasone
      (VAD) therapy on the same parameters and mediators as well as the relationship
      among the parameters in the same patient groups. The serum concentrations of TNF
      alpha, IL-1beta, sIL-2R, IL-6, IL-8, and CRP (18.6 +/- 3.7 pg/mL, 10.1 +/- 2.8
      pg/mL, 730 +/- 220 U/mL, 11.4 +/- 3.3 pg/mL, 23.9 +/- 8.3 pg/mL, and 49.9 +/-
      19.5 mg/dL, resp) were significantly higher in newly diagnosed MM patients than
      in healthy controls (P < .0001). All of the parameters were found to be
      significantly reduced after chemotherapy. In conclusion, we found that after the
      VAD therapy, the level of these cytokines which are thought to play an important
      role in the pathogenesis of MM was significantly suppressed. This is the first
      study demonstrating strong impact of VAD treatment on circulating mediators of
      sIL-2R and IL-8 levels parameters.

PMID- 16106105
TI  - Serum levels of the MCP-1 chemokine in patients with ischemic stroke and
      myocardial infarction.
AB  - Chemokine-driven migration of inflammatory cells has been implicated in
      pathogenesis of atherosclerosis-associated conditions such as ischemic stroke and
      myocardial infarction. In this study, a candidate chemokine, monocyte
      chemoattractant protein (MCP)-1, was investigated in patients with both
      aforementioned manifestations of atheroslerotic inflammation. MCP-1 levels in
      serum were determined by ELISA in 40 healthy, control subjects (C), 40 patients
      with ischemic stroke (IS), and in 64 patients with myocardial infarction (MI).
      Statistical analysis utilised Mann-Whitney test, Fisher's exact test, and
      Spearman's rank correlation (P < .05). In comparison to control subjects (C;
      median/interquartile range: 239/126 pg/mL), MCP-1 serum levels were increased in
      both investigated patient cohorts (IS: 384/370, P < .001; MI: 360/200, P < .002).
      There was a substantial variability of MCP-1 serum levels, especially in the IS
      group. No relationship was observed between chemokine levels and atherosclerosis
      risk factors (hypertension, diabetes, smoking, and alcohol consumption), and MCP
      1 was also not related to age or gender. Elevation of MCP-1 in circulation of
      patients with atherosclerosis-associated complications implicates this CC
      chemokine ligand (CCL)2 in inflammatory processes, which contribute to
      pathogenesis of myocardial infarction and ischemic stroke. Further
      investigations, including patient stratification, are however necessary to
      evaluate if MCP-1 can be utilised for clinical management of patients with these
      diseases.

PMID- 16106106
TI  - Proinflammatory cytokines and leptin are increased in serum of prepubertal obese
      children.
AB  - It has not yet been shown in prepubertal children how cytokines, leptin, and body
      mass, as well as parameters of obesity are interrelated. The aim of this study
      was to explore the relation between circulating levels of some cytokines with
      leptin and body mass index. A case control study was carried out in obese
      children of both sexes. An obese group was carried out with 63 school prepubertal
      children and a control group comprised the same number of nonobese children
      paired by age and by sex. Mean serum leptin concentration was significantly
      higher in the obese children at 19.9 +/- 7.4 ng/mL, than the control group (7.9
      +/- 5.1 ng/mL). Serum IL-1beta, IL-6, and TNF-alpha levels were also
      significantly higher in the obese group than controls (33.0 +/- 8.9, 45.2 +/-
      11.8, and 9.2 +/- 2.3 pg/mL, versus 3.6 +/- 1.0, 13.1 +/- 3.9, and 3.9 +/- 1.0
      pg/mL, resp). In controversy, serum IL-2 level was diminished in the obese group
      as 0.4 +/- 0.1 versus 0.9 +/- 0.1 U/L. Obesity may be a low-grade systemic
      inflammatory disease. Obese prepubertal children have elevated serum levels of IL
      1beta , IL-6, and TNF-alpha which are known as markers of inflammation.

PMID- 16106107
TI  - Venobronchial fistula: an unusual complication of long-term central venous
      access.
AB  - A venobronchial fistula developed between the azygous vein and the upper aspect
      of the right main bronchus 12 months after completion of the treatment of a stage
      IIIB non-small-cell lung cancer in a 54-year-old man. The fistula contained the
      tip of the catheter placed for chemotherapy perfusion. The reported case
      presented risk factors previously identified for such a complication. In
      addition, some clinical particularities were present, suggesting new potent risk
      factors and some preventive means for safe long-term central venous
      catheterization.

PMID- 16106108
TI  - Tweezers in the right bronchial system.

PMID- 16106109
TI  - Nitric acid-induced bronchiolitis in rats mimics childhood Bronchiolitis
      obliterans.
AB  - BACKGROUND: Childhood bronchiolitis obliterans (CBO) is an infrequent but severe
      disease, characterized by persistent obstructive respiratory symptoms after an
      acute episode of bronchiolitis. Its etiology is mostly postviral, especially in
      developing countries. Pathologically, CBO is characterized as constrictive-type
      BO. The pathogenesis of this disease is poorly understood and there is no
      specific treatment. Animal models could help to better understand the sequence of
      events culminating in bronchiolar obliteration and serve as basis for
      experimental therapeutic research. OBJECTIVES: In this study, we adapted the
      nitric acid (NA) technique to develop a suitable model to study CBO in rats.
      METHODS: We have intratracheally instilled 0.5% NA or saline and studied the
      histological lesions on days 2, 7, 14 and 30. NA-instilled animals developed a
      sequence of bronchiolar lesions that included necrotizing bronchiolitis,
      proliferative (PROL) bronchiolar lesions and constrictive (CONS) bronchiolar
      lesions with bronchiectasis, mucostasis and macrophagic accumulation. RESULTS:
      The frequency of PROL lesions decreased and that of the CONS lesions increased,
      with a statistically significant difference at the sacrifice days, except for day
      7 (PROL vs. CONS lesions day 2: p = 0.001; PROL vs. CONS lesions day 7: p = 0.38;
      PROL vs. CONS lesions day 14: p < 0.001; PROL vs. CONS lesions day 30: p <
      0.001). CONCLUSIONS: We conclude that this model presents histological
      similarities with the histological picture of CBO, being suitable for further
      developmental and therapeutic experimental research in this field.

PMID- 16106111
TI  - Factors influencing length of hospital stay in patients with bacterial pleural
      effusion.
AB  - BACKGROUND: Factors influencing length of hospital stay have been poorly analyzed
      in parapneumonic pleural effusions (PPE). OBJECTIVES: The aim of this work is to
      identify the variables that determine increased hospital stay in patients with
      infectious pleural effusion (PE). PATIENTS AND METHODS: We analyzed 112 patients
      with PE: empyema, complicated parapneumonic and non-complicated parapneumonic.
      Epidemiologic, biochemical, therapeutic and radiological variables were analyzed.
      Correlations with hospital stay were studied using the Student's t test, analysis
      of variance, Mann-Whitney U-test and linear regression model. RESULTS: Among the
      112 patients studied, there were 32 empyema, 50 complicated and 30 non
      complicated parapneumonic cases. The median of length stay for all patients was
      17 days. Longer hospitalization was required in patients with empyemic PE (p =
      0.015), patients with underlying diseases (p = 0.003), those needing pleural
      drainage (p = 0.005) or decortication (p = 0.043) and those presenting
      unfavorable radiological outcome after treatment (p = 0.02). Biochemical
      parameters associated with longer hospital stay were elevated pleural fluid
      polymorphonuclear elastase (p = 0.001, r = 0.307) and lactate dehydrogenase (p =
      0.001, r = 0.312). After linear regression analysis, only underlying disease,
      pleural drainage and pleural fluid polymorphonuclear elastase values remained in
      the model, explaining 23.1% of the variability of days of hospitalization.
      CONCLUSIONS: The patients with PPE and empyema who required longer
      hospitalization were those with purulent fluid, underlying disease, surgical
      drainage and/or decortication, with unfavorable radiological outcome and higher
      pleural fluid levels of lactate dehydrogenase and polymorphonuclear elastase.

PMID- 16106112
TI  - Diffuse pulmonary arteriovenous malformations in a teenager with corrected total
      anomalous pulmonary venous drainage.
AB  - This case report describes a 13-year-old boy with diffuse microvascular pulmonary
      arteriovenous malformations, in whom total anomalous pulmonary venous drainage
      had been corrected surgically in the newborn period. Contrast transesophageal
      echocardiography, cardiac catheterization and a lung perfusion scan suggested,
      and lung biopsy confirmed the diagnosis in our patient. Treatment with nifedipin
      was commenced. CONCLUSION: This case illustrates the diagnostic difficulties with
      this rare malformation.

PMID- 16106113
TI  - Breathing movements and breathing patterns among healthy men and women 20-69
      years of age. Reference values.
AB  - BACKGROUND: Measurements in absolute terms of the whole respiratory movement
      pattern (range, type, symmetry, rhythm and frequency of breathing movements) of
      healthy individuals are valuable for reference, when assessing patients with
      conditions affecting respiration. OBJECTIVE: To establish reference data for
      breathing movements and patterns for healthy men and women. METHODS: Fifty men
      (mean age 47.8 years) and 50 women (mean age 43.4 years) aged between 20 and 69
      years participated in the study. Anterior-posterior breathing movements of the
      upper and lower thorax and abdomen were measured bilaterally during quiet
      breathing and deep breathing using the respiratory movement measuring instrument.
      Descriptive statistics, paired-sample statistics and Kendall's correlation test
      were used for analysis. RESULTS: Breathing movements were symmetrical and did not
      change significantly with increasing age. The average breathing type for men and
      women was abdominal during quiet breathing. During deep breathing the abdominal
      movements were significantly less amongst the women than the men (p < 0.05). The
      average respiratory rate was 14 during quiet and 7.4 during deep breathing for
      both sexes. The rhythm (inspiration/expiration ratio) was 1:1.21 for men and
      1:1.14 for women during quiet breathing and 1:1.23 for men and 1:1.40 for women
      during deep breathing. CONCLUSIONS: As men and women have similar breathing
      movements during quiet breathing their reference values can be combined. On the
      other hand, separate reference values are needed for men and women for deep
      breathing.

PMID- 16106114
TI  - Increased expression of CD86 and reduced production of IL-12 and IL-10 by
      monocyte-derived dendritic cells from allergic asthmatics and their effects on
      Th1- and Th2-type cytokine balance.
AB  - BACKGROUND: In allergic asthma, allergen-specific T cells have a Th2-biased
      phenotype, and it is thought that dendritic cells (DCs) contribute to the
      induction of allergic immune responses. Therefore, we hypothesized that DCs from
      allergic asthmatics and healthy donors differ with regard to their preference to
      induce Th1 or Th2 immune responses. OBJECTIVES: To investigate differences in DC
      expressed costimulatory molecules and DC-secreted cytokines between allergic
      asthmatics and healthy donors, and their influence on the Th1- and Th2-type
      cytokine balance. METHODS: Circulating monocytes from patients with allergic
      asthma and healthy donors were cultured with GM-CSF and IL-4, respectively, for 5
      days and subsequently with lipopolysaccharide for 2 days to create mature DCs
      (mDCs). CD1a, CD83, CD40 and CD86 expression on mDCs was examined using a
      fluorescence-activated cell sorter. IL-12 and IL-10 secreted by mDCs were
      measured by ELISA. Naive cord blood T cells were primed by mDCs from two groups,
      and IL-4 and IFN-gamma production by polarized T-helper cells (Th) was measured
      by ELISA. RESULTS: (1) CD86 expression on mDCs from allergic asthmatics was
      higher than that from healthy donors. (2) IL-12, IL-12p40 and IL-10 production by
      mDCs from allergic asthmatics was significantly lower than that from healthy
      donors, respectively. (3) IL-4 production by Th cells primed by mDCs from
      allergic asthmatics was increased compared with that from healthy donors.
      CONCLUSIONS: mDCs from allergic asthmatics preferentially priming naive T cells
      towards Th2-cell development might be due to increased expression of CD86 and
      reduced production of IL-12 and IL-10.

PMID- 16106115
TI  - Burden and coping strategies in families of patients under noninvasive home
      mechanical ventilation.
AB  - BACKGROUND: It is well documented that caregivers of patients with chronic
      respiratory failure under noninvasive mechanical ventilation (NIMV) are at high
      risk to develop depression, burden, overload and declining health over time.
      OBJECTIVES: The purpose of the study was to investigate the subjective and
      objective burden imposed on families of patients under NIMV at home and explore
      the coping strategies they adopt. METHODS: The study population consisted of 50
      informal caregivers of patients with chronic respiratory failure under NIMV at
      home for at least 6 months. The burden of the families, as well as the adaptation
      strategies, were estimated by a modified version of the Family Burden
      Questionnaire validated in Greek. RESULTS: Profound objective burden was reported
      in the field of social relations in 49%, in household management in 43.2%, in
      financial issues in 31.3% and in employment issues in 29.4% of the families. The
      subjective burden which the families experienced was usually lower and it was
      reported in household management in 33.4%, in employment issues in 29.4%, in
      social relations in 21.6% and in financial issues in 21.5% of the families. The
      strategies adopted by the families in order to cope with the imposed burden
      included reorientation of goals in 92.2%, resignation in 88.2%, passivity in
      62.7%, hopefulness in 45.3%, ambivalence in 19.6% and guilt in 13.7% of the
      families. CONCLUSIONS: The families of patients under NIMV seem to face major
      problems (severe burden) in household management and their social relations.
      Families do not seem to subjectively experience the burden that is objectively
      recorded and, in the vast majority, they adopt healthy coping strategies.

PMID- 16106116
TI  - Pulmonary infection with Cryptococcus neoformans in the face of underlying
      sarcoidosis.
AB  - We present a case of limited pulmonary cryptococcal infection following exposure
      to pigeon excreta in a patient with sarcoidosis. The pathogenicity of
      Cryptococcus neoformans depends on the interplay between the immune status of the
      host and the virulence of the infecting strain. It can range from asymptomatic
      lung colonization in the immunocompetent host to rapidly progressive meningitis
      in immunocompromised patients. Immunological models of respiratory disease
      emphasize a distinction between infections associated with immune suppression on
      the one hand and diseases such as sarcoidosis believed to involve an excessive
      Th1-mediated immune response on the other. This case exemplifies the complex
      nature of immunological responses in the lung and highlights the importance of
      considering the possibility of co-existent fungal infection in individuals with
      sarcoidosis. Novel immunotherapeutic options for cryptococcal infection are
      discussed.

PMID- 16106118
TI  - Intrathoracic impedance to monitor heart failure status: a comparison of two
      methods in a chronic heart failure dog model.
AB  - In patients with heart failure (HF), a convenient and accurate assessment of HF
      status could enhance titration of medications and possibly reduce
      hospitalizations for fluid overload. This study examined the feasibility of
      monitoring HF status by measuring intrathoracic impedance with either an
      implantable cardioverter-defibrillator or a pacemaker. Six canines were each
      instrumented with four devices: two capable of measuring intrathoracic impedance
      between a right ventricular coil electrode and the device case, one custom
      pacemaker for inducing HF, and an implantable hemodynamic monitor to measure left
      ventricular end-diastolic pressure as an assessment of HF status. High-rate
      ventricular pacing for 3-7 weeks induced HF, followed by a 4-week recovery
      period. During high-rate pacing, left ventricular end-diastolic pressure was
      inversely correlated with impedance measurements from both systems (median r=
      0.66; range r=-0.38 to -0.81). During recovery, the inverse correlation between
      left ventricular end-diastolic pressure and impedance was enhanced (median r=
      0.88; range r=-0.58 to -0.95). The two types of impedance measurements were
      highly correlated (median r=-0.68 during pacing and r=-0.91 during recovery).
      These results suggest that various methods of measurement of intrathoracic
      impedance over time could be used to monitor HF status.

PMID- 16106119
TI  - Vascular thrombosis during support with continuous flow ventricular assist
      devices: correlation with computerized flow simulations.
AB  - Continuous flow pumps are increasingly used to treat severe heart failure. These
      pumps alter flow physiology by lowering pulsatility in the arterial circulation.
      In patients with peripheral stenosis, continuous flow pumps may lead to
      thrombosis of peripheral vessels, possibly predisposing to vascular thrombosis in
      areas of non-flow-limiting stenosis. The authors performed a computerized flow
      modeling simulation to analyze the effects of altered hemodynamics in a stenotic
      area. Drawing on previous clinical experience, we modeled a stenotic area in the
      common carotid artery. Computerized flow modeling revealed blood stagnation zones
      with low shear stress and velocity adjacent to the stenotic area during
      nonpulsatile flow. Such stagnation was not present during pulsatile flow. These
      results indicate a mechanism by which altered physiologic flow may accelerate
      occlusion of arterial conduits in patients with preexisting stenosis. This
      finding may be important for patients with continuous flow devices who have
      peripheral vascular disease; therefore, further study is warranted.

PMID- 16106120
TI  - Left ventricular assist device therapy for end-stage congestive heart failure:
      from REMATCH to the future.
AB  - Therapy for patients with end-stage cardiomyopathy continues to evolve, but
      clearly it must now involve left ventricular assist device therapy as either
      bridge-to-transplantation or destination therapy. Patients who are selected for
      left ventricular assist device support must be able to undergo the surgical
      implantation procedure safely and avoid common complications such as right heart
      failure. Adequate patient selection is essential and can typically be
      accomplished using simple hemodynamic measures. As left ventricular assist device
      technology evolves, pulsatile devices will likely be replaced by their newer
      axial flow counterparts, which offer decided advantages. In the future, therapy
      for end-stage heart failure will involve aggressive use of mechanical assist
      device therapy and, as more patients are supported with these devices and the
      technology improves, this will become a burgeoning field for cardiologists and
      cardiovascular surgeons.

PMID- 16106121
TI  - Cost-effective strategies to screen for left ventricular systolic dysfunction in
      the community--a concept.
AB  - Early detection of heart failure caused by left ventricular systolic dysfunction
      (LVSD) is important, since early treatment has been shown to retard the
      progression of heart failure. While traditional echocardiography remains the
      standard for the detection of LVSD, electrocardiography and serum brain
      natriuretic peptide have also been shown to predict LVSD. Recently, hand-held
      echocardiography systems have been shown to have high predictive accuracy for
      assessment of LVSD. With the availability of the above bedside and relatively
      less-costly techniques, compared with traditional echocardiography, the major
      question now is what is the most cost-effective strategy for screening subjects
      for LVSD. To date, no studies have systematically addressed this issue, but
      preliminary data are becoming available. This review article discusses the pros
      and cons of various investigative strategies and likely cost-effectiveness of
      each strategy to screen for LVSD.

PMID- 16106122
TI  - Cardiac resynchronization therapy and tools to identify responders.
AB  - Heart failure is a major epidemic. Many people with heart failure struggle with
      refractory symptoms despite optimal medical therapy. Those with severe left
      ventricular dysfunction and ventricular conduction delay are at significant risk
      from either dying suddenly or dying from progression of their heart failure.
      Cardiac resynchronization therapy (CRT) improves hemodynamics and symptoms of
      heart failure and has recently been shown to improve survival. One problem facing
      the use of CRT is that 30% of patients fail to respond. The dominant theory is
      that QRS duration (electrical dyssynchrony) does not accurately reflect
      mechanical dyssynchrony. Echocardiographic tools have recently been developed
      that enable clinicians to assess the degree of mechanical dyssynchrony in
      patients being considered for CRT. These tools are able to predict with a
      significant amount of accuracy whether a patient will respond to CRT. This allows
      for a more refined approach to evaluating patients for CRT and optimizing the
      treatment of congestive heart failure.

PMID- 16106123
TI  - A US Food and Drug Administration perspective on cardiac resynchronization and
      ventricular assist device trials.
AB  - Cardiac resynchronization therapy and ventricular assist devices are two of the
      many US Food and Drug Administration-regulated medical device technologies that
      are intended for patients with heart failure. Cardiac resynchronization therapy
      devices have been shown to significantly improve the quality and potentially the
      duration of life for patients with moderate-to-severe congestive heart failure
      and electrical dyssynchrony. Likewise, ventricular assist devices have benefited
      patients with end-stage heart failure through both bridge-to-transplant and
      destination therapy. The pivotal trials that supported the first approvals for
      these devices, as well as subsequent trials, were shaped by unique technologic
      and patient-related concerns. The US Food and Drug Administration has worked to
      understand these evolving concerns and the role each should play in the design of
      trials intended to demonstrate the safety and effectiveness of these critical
      devices.

PMID- 16106124
TI  - Current and emerging issues with B-type natriuretic peptide. Roundtable
      discussion.
AB  - A brief panel discussion was held on March 23, 2005, in New York City following a
      live symposium for primary care physicians discussing the roles of B-type
      natriuretic peptide in a variety of cardiovascular diseases. The participants
      were Dr. Marc A. Silver, Advocate Christ Medical Center, Oak Lawn, IL; Dr. Clive
      Rosendorff, Mount Sinai School of Medicine, New York, NY and VA Medical Center,
      Bronx, NY; Dr. Robert Berkowitz, Hackensack University Medical Center,
      Hackensack, NJ; and Dr. W. Franklin Peacock IV, The Cleveland Clinic Department
      of Emergency Medicine, Cleveland, OH. Dr. Silver moderated the discussion. The
      panel gathered to review some of the questions that emerged from the symposium
      and the questions raised by the attendees. These are of interest and importance
      to all interested in heart failure and B-type natriuretic peptide.

PMID- 16106125
TI  - Heart failure advances... going to the dogs.

PMID- 16106128
TI  - Historical vignettes in heart failure. History of heart failure.

PMID- 16106129
TI  - Cardiac unilateral pulmonary edema: is it really a rare presentation?
AB  - Unilateral pulmonary edema is a distinctly unusual clinical entity that presents
      interesting and confusing diagnostic challenges. It is usually described as
      occurring with re-expansion of a collapsed lung after rapid thoracocentesis of
      pleural air or pleural fluid. Unilateral pulmonary edema as an initial presenting
      manifestation for heart failure is uncommon and can be confused with other more
      common causes of alveolar or interstitial infiltrate, which can lead to a
      significant delay in treatment.

PMID- 16106130
TI  - Cardiovascular events in hypertension trials of Angiotensin-converting enzyme
      inhibitors.
AB  - Angiotensin-converting enzyme inhibitors are widely-prescribed drugs for
      hypertension and are supported by clinical trials in which they reduce
      cardiovascular events. In the high-risk patients in the Heart Outcomes Prevention
      Evaluation, the Perindopril Protection Against Recurrent Stroke Study, and
      European Trial of Reduction of Cardiac Events With Perindopril in Stable Coronary
      Artery Disease, ramipril and perindopril showed impressive benefits. One reason
      trandolapril did somewhat less well in the Prevention of Events With Angiotensin
      Converting Enzyme Inhibition trial may be that its patients were very well
      treated with other effective modalities. In the Antihypertensive and Lipid
      Lowering to Prevent Heart Attack Trial, lisinopril-treated patients had a
      slightly lower incidence of myocardial infarction, despite much poorer control of
      blood pressure, perhaps because a second-line diuretic was prohibited by
      protocol. Although angiotensin-converting enzyme inhibitors can cause cough and
      angioedema (more common among blacks), angiotensin receptor blockers are
      currently more expensive and have fewer outcome trials to support their use.

PMID- 16106131
TI  - Your drug, my drug, or our drugs: how aggressive should we be with
      antihypertensive therapy?
AB  - In the prevention of hypertensive complications, especially stroke and kidney
      disease, "lower is better" because for each decrease of 20 mm Hg systolic or 10
      mm Hg diastolic pressure in the population, cardiovascular risk is halved.
      Ideally, the goal for each patient should be to reach the lowest blood pressure
      that is well tolerated, a value that may be well below the arbitrary threshold
      value of 140/90 mm Hg. For the majority of "uncomplicated hypertensives," the
      question of single-drug therapy is essentially moot, because more than one agent
      is almost always required to optimally control blood pressure. In individuals who
      already have heart or kidney disease, there are compelling indications for the
      use of drugs that block the renin-angiotensin system, but the large outcome
      studies that spawned these recommendations are themselves combination trials.
      Thus, in virtually all patients, more than one drug is indicated. The best
      combinations take advantage of long durations of action and complementary
      mechanisms of action of the component and are not only able to effectively lower
      blood pressure, but also to favorably affect the natural history of hypertensive
      complications. Regimens-including fixed-dose combination products-that combine a
      thiazide diuretic or calcium antagonist with an angiotensin-converting enzyme
      inhibitor or angiotensin receptor blocker are most efficient. In summary, why
      would an astute clinician (or informed patient) be satisfied with the relatively
      limited effects of any single class of antihypertensive agents when better
      overall protection is possible?

PMID- 16106132
TI  - Angiotensin-converting enzyme inhibitor use in the year 2005.
AB  - The angiotensin-converting enzyme (ACE) inhibitor drug class is one with
      considerable staying power. ACE inhibitors are not only well established
      antihypertensive agents but also are compounds that fairly regularly provide end
      organ protection. Several of the ACE inhibitors are entangled in an active debate
      regarding class effect. Class effect for ACE inhibitors is a hopelessly confused
      term because its definition is not standardized and is subject to interpretation
      that in many cases is self-serving. For the most part, ACE inhibitor side effects
      are readily identifiable, and management strategies put in place can be logical
      and sequential. The future of this drug class remains bright. Other drug classes,
      such as angiotensin receptor blockers, have narrowed-but not entirely closed-the
      outcomes gap that exists between these two drug classes.

PMID- 16106134
TI  - An overview of myoblast transplantation for myocardial regeneration.
AB  - Regenerative medicine represents a new frontier in treatment of disease,
      particularly cardiovascular disease. The contractile elements of the heart,
      cardiomyocytes, lack the capacity for any postnatal proliferation or
      regeneration. Therefore, repair of heart damage can be achieved only by
      manipulating cardiomyocytes to regrow or by introducing exogenous cells with the
      capacity to restore function to the myocardium. Many attempts have been made with
      various cell types to repair the damaged myocardium. We will present here a
      summary of some of those studies and also present in detail studies utilizing a
      promising, near-term, and practical source of cells for treatment of heart
      disease: autologous skeletal myoblasts.

PMID- 16106135
TI  - Management of acute and chronic heart failure with left ventricular assist
      devices.
AB  - The prevalence and incidence of heart failure is on the rise. Due to the lack of
      donor organs, cardiac transplantation can have only a minimal epidemiologic
      impact. Advances in left ventricular assist device development and experience
      with management and surgical implantation techniques have slowly improved the
      field, and the use of these devices to treat severe heart failure is gaining
      acceptance. The Texas Heart Institute has remained at the forefront of artificial
      heart research, currently utilizing both short- and long-term devices as bridge
      to-transplant, bridge-to-recovery, or destination therapy. These devices provide
      varying degrees of support and, depending on their design, are implanted either
      surgically in the operating room or percutaneously in the cardiac catheterization
      laboratory. Despite the remarkable progress in left ventricular assist device
      development, there are several improvements to be made that may potentially
      increase their acceptance by patients and referring doctors.

PMID- 16106136
TI  - Potential indications for coronary angiography by computed tomography.
AB  - Recent advances in computed tomography technology have made possible angiographic
      images of relatively small, moving vascular structures such as the coronary
      arteries. Computed tomographic coronary angiography is an exciting modality which
      has several obvious advantages over invasive catheterization, such as its
      relatively noninvasive nature and rapid speed of acquisition. However,
      significant drawbacks still exist, including limitations of spatial and temporal
      resolution and radiation exposure. Computed tomographic coronary angiography
      appears best suited as a diagnostic modality for the patient population with a
      low-to-moderate pretest probability of coronary artery disease, and for specific
      indications such as the imaging of coronary anomalies and bypass grafts and
      before biventricular pacemaker placement and atrial fibrillation ablation.

PMID- 16106137
TI  - Novel developments in cardiac computed tomography.
AB  - Recent advances in computed tomography have the potential to change the way
      imaging is performed in the detection of coronary artery disease. The current
      generation of scanners offers the ability to rapidly acquire thin sections in
      conjunction with the electrocardiogram, allowing for both anatomic and
      physiologic data to be obtained. These advancements hold the promise for a
      noninvasive means of directly evaluating the coronary arteries that can be
      applied in every day practice. This article reviews the advances in technology
      and their implications for imaging the heart.

PMID- 16106138
TI  - What is the evidence for percutaneous coronary intervention or coronary artery
      bypass graft in ischemic cardiomyopathy?
AB  - Coronary artery disease has supplanted hypertension as the leading cause of
      congestive heart failure in the United States. The recognition that contraction
      abnormalities could accrue from gradual stunning, or longer-term 'hibernation,'
      raised the possibility that revascularization of viable but hypocontractile
      elements could improve myocardial performance. This review focuses on the data
      from randomized trials and registries regarding the potential benefits and risks
      of either coronary artery bypass grafting (CABG) or percutaneous coronary
      intervention for patients with severe left ventricular dysfunction secondary to
      coronary artery disease. For patients with medically refractory angina and
      ischemic cardiomyopathy, revascularization with CABG or percutaneous coronary
      intervention is recommended. The ongoing National Institutes of Health-sponsored
      Surgical Treatment for Ischemic Heart Failure (STICH) trial, a multicenter,
      prospective, randomized trial comparing contemporary medical therapy with CABG
      for patients with ischemic cardiomyopathy, should provide important information
      regarding patients who do not have angina. The conclusion of this review is that
      a trial of medical therapy vs. percutaneous coronary intervention could be of
      additional value, especially for patients at particularly high risk, when
      undergoing CABG.

PMID- 16106139
TI  - Direct stenting with sirolimus-eluting stents.
AB  - The sirolimus-eluting stent has been studied extensively in randomized controlled
      trials of patients with native de novo coronary lesions. Lesion predilation
      before stent placement has been the predominant implantation strategy in these
      trials. Direct implantation of the sirolimus-eluting stent without lesion
      predilation has been undertaken at the investigators' discretion in certain
      trials as well as in patients enrolled in a post-marketing surveillance registry,
      and was the intended implantation strategy in the DIRECT trial. Comparisons with
      patients receiving sirolimus-eluting stents after lesion predilation in the
      trials and the registry were all confounded by imbalances in patient, lesion,
      and/or procedural characteristics and point to the highly selective nature of the
      direct-stenting strategy. At present, direct implantation of the sirolimus
      eluting stent appears to be safe and as effective as conventional (predilated)
      stenting, provided that the targeted coronary lesion is amenable to the direct
      approach. Since a randomized trial of implantation strategies is lacking, there
      is no conclusive evidence as to the hypothesized superiority of direct over
      predilated stenting in suitable coronary lesions.

PMID- 16106140
TI  - Evaluating cardiovascular pathophysiology and anatomy in atherosclerosis.
AB  - The process of atherosclerosis begins with endothelial dysfunction from impaired
      bioavailability of NO and progresses through multiple stages of plaque
      development. Impaired endothelial function decreases NO and increases oxidized
      macromolecules such as low-density lipoprotein cholesterol. Oxidized low-density
      lipoprotein cholesterol accumulates in subendothelial space, forming plaques that
      may eventually compromise the lumen. Acute coronary events result from plaque
      rupture and consequent thrombus formation and abrupt occlusion of the vessel
      lumen. New diagnostic methods such as flow-mediated dilation of the brachial
      artery can detect endothelial dysfunction, and intravascular ultrasound can
      detect early plaque formation in the arterial wall. These techniques may provide
      a means to identify patients at risk for adverse cardiovascular outcomes, thereby
      enabling physicians to potentially prevent adverse events by early initiation of
      lipid-lowering therapy.

PMID- 16106141
TI  - The electronic health record--the time is now.
AB  - Health care is changing because of the need to effectively manage both acute and
      chronic illness in the delivery of quality patient-centered care. This will force
      a change from the physician-centric model to one that uses a care team approach
      in both the hospital and ambulatory settings. The electronic health record
      promotes communication among team members, knowledge management, and the need to
      more rapidly translate evidence-based guidelines and performance criteria to the
      bedside and office. Electronic health records with embedded clinical decision
      support systems hold great promise. Multiple parties are pushing this agenda
      forward, which will lead to more comprehensive, efficient quality care. Use of
      the quality improvement tool as described shows how effective these methods are
      in managing coronary artery disease. Physicians and all members of the care team
      need to embrace this evolution.

PMID- 16106142
TI  - Pretty pictures: CT angiography and collaboration among specialties.

PMID- 16106143
TI  - Late thrombosis associated with drug-eluting stents.

PMID- 16106144
TI  - Primary prevention implantable cardioverter-defibrillators: economics and ethics.

PMID- 16106145
TI  - The dawn of open heart surgery: an overview of the symposium that celebrated the
      50th anniversary of controlled cross circulation.
AB  - At the 50th Anniversary of Open Heart Surgery symposium sponsored by the Lillehei
      Heart Institute of the University of Minnesota in October 2004, the following
      pioneers in open heart surgery development presented papers of historical
      interest: Drs. Peter Agre, Robert W. Anderson, William Baumgartner, Alain
      Carpentier, Aldo Casteneda, Randolph Chitwood, Jr., Denton Cooley, Fred Crawford,
      Michael DeBakey, Richard DeWall, Vincent Gott, Claude Lenfant, Floyd Loop, James
      Holler, Glen Nelson, Norman Shumway, Manny Villafana, Richard Weisel, and Sir
      Magdi Yacoub.

PMID- 16106146
TI  - Prosthetic valve malfunction: a sticky situation.

PMID- 16106147
TI  - Wolff-Parkinson-White ECG with false infarct.

PMID- 16106149
TI  - Examining the margins: a concept analysis of marginalization.
AB  - The aim of this analysis is to explore the concept of social marginalization for
      the purpose of concept development. Specifically, the article intends to clarify
      the relationship between health disparities and marginalization and generate
      knowledge about working with people who are socially marginalized. Concept
      development evolved from the critical analysis of relevant literature generated
      through searches of nursing and social science databases. Literature was
      organized thematically and themes related to marginalization as a social process
      were included and analyzed. The article explores the challenges of using
      marginalization as an independent concept and suggests areas for future inquiry
      and research.

PMID- 16106150
TI  - Health disparities in the context of mixed race: challenging the ideology of
      race.
AB  - Debates are occurring about the relative contribution of genetic versus social
      factors to racial health disparities. An ideology of race is manifested in
      genetic arguments for the etiology of racial health disparities. There is also
      growing attention to people of mixed race since the 2000 US Census enabled them
      to be counted. Consideration of the complex issues raised by the existence of
      people of mixed race may bring clarity to the debates about racial health
      disparities, offer a challenge to the ideology of race, and afford important
      insights for the practice of research involving race.

PMID- 16106151
TI  - Speaking truth to power: nursing's legacy and moral imperative.
AB  - Critical caring has been proposed as a mid-range theory to guide public health
      nursing. One of its carative health promoting processes, contributing to the
      creation of supportive and sustainable physical, social, political, and economic
      environments, is particularly suited to enacting Nightingale's legacy of
      political action as an expression of caring. Increasing evidence supports the
      link between broad societal influences on health inequities. Relative and
      absolute poverty are significant influences on health and contribute
      significantly to differential health statuses of populations within and between
      countries. Nurses, who practice at the intersection of public policy and personal
      lives, are, therefore, ideally situated and morally obligated to include
      political advocacy and efforts to influence health public policy in their
      practice. The health of the public and the future of the profession may depend on
      it.

PMID- 16106152
TI  - A theoretical model of social consciousness.
AB  - The article presents a theoretical model of social consciousness developed from
      nurses' life histories. A 3-position dialectical framework--acquired, awakened,
      and expanded social consciousness--makes visible the way people respond to social
      injustice in their lives and in the lives of others. The positions coexist, are
      not hierarchical, and are contextually situated. A person's location influences
      her or his availability for social action. Nurses who could most contribute to
      challenging social injustices that underpin health disparities are relegated to
      the margins of mainstream nursing by internal processes of discrimination. More
      inclusive definitions of "a nurse" would open up possibilities for social change.

PMID- 16106153
TI  - Mental health of undocumented Mexican immigrants: a review of the literature.
AB  - The Latino population in the United States, the majority of whom are Mexican, is
      one of the fastest growing. Similarly, the number of undocumented Mexican
      immigrants (UMIs) continues to swell. However, little is known about UMIs living
      in the United States, and much less is known about their mental health status.
      This interdisciplinary review of the literature aims to outline the current state
      of knowledge regarding the mental health of UMIs in the United States. Themes
      isolated from the literature include failure to succeed in the country of origin;
      dangerous border crossings; limited resources; restricted mobility;
      marginalization/isolation; blame/stigmatization and guilt/shame;
      vulnerability/exploitability; fear/fear-based behaviors; and stress, depression,
      and health implications.

PMID- 16106154
TI  - Health disparity and the nurse advocate: reaching out to alleviate suffering.
AB  - This article reviews current research in health disparity in the delivery of care
      to African Americans. These studies provide powerful evidence that, even when
      controlling for differences related to access, insurance, and socioeconomic
      status, our healthcare system is deeply racist. While it is difficult to estimate
      the cost of racial bias in healthcare delivery, this article advances the notion
      that human suffering is the most significant consequence of racial disparity.
      Solutions include a renewed commitment to increasing cultural knowledge, a
      concerted effort to recognizing and studying racism, and creating a role for the
      community nurse advocate in correcting disparity.

PMID- 16106155
TI  - Maintaining normalcy: a grounded theory of engaging in HIV-oriented primary
      medical care.
AB  - Despite advances in the medical treatment of HIV disease, marginalized
      populations continue to shoulder a disproportionate burden of HIV/AIDS-related
      morbidity and mortality. This study explored the process by which clients at HIV
      oriented primary care clinics transition from being sporadic users of care to
      engaging as regular users of care. A model illustrating how participants were
      striving to maintain normalcy, manage perceptions, and develop life mastery
      skills contributes to an understanding of living with HIV disease in a social
      context. Elements of the model are sensitive to nursing interventions aimed at
      improving health outcomes and reducing health disparities among persons at
      highest risk.

PMID- 16106156
TI  - Using marginalization theory to examine pedestrian injury: a case study.
AB  - Hall, Stevens, and Meleis' critical feminist theory of marginalization provides a
      useful lens through which to examine both the role of the automobile in Western
      society and the related phenomenon of automobile-pedestrian injury. This article
      draws on a specific case of automobile-pedestrian fatality in San Francisco's
      Mission District to show how the marginalization of neighborhoods, groups, and
      individuals occurs in an autocentric environment. Nurses can use concepts of
      marginalization to inform and dialogue with communities about healthier, safer
      transportation options and ways to achieve them.

PMID- 16106157
TI  - Quality of life after breast reduction.
AB  - The purpose of this study is to compare health-related quality of life in women
      with symptomatic macromastia before and after breast reduction. Two comparable
      groups of women were enrolled in the study, those waiting for breast reduction
      (group 1) and those who underwent surgery approximately 2 years before (group 2).
      To evaluate the specific beneficial effects of breast reduction, we used a unique
      combination of general and specific questionnaires: the Short Form 36 Health
      Survey Questionnaire (SF-36), the European Quality of Life-5 Dimensions (EQ-5D),
      the Rosenberg Self-Esteem Scale (RSE), the Self-Consciousness Scale (SCS), and
      the Derriford Appearance Scale 59 (DAS-59). The esthetic appearance of the breast
      was also evaluated using a visual analog scale (VAS). In both groups,
      preoperative back pain was present in more than 50% of patients. Complaints were
      significantly reduced after surgery. SF-36 showed significant higher quality of
      life in group 2 with regard to 7 of 8 investigated domains. Increased self-esteem
      after surgery, increased personal and public self-consciousness were observed.
      Moreover, the condition-specific DAS-59 showed that insecurity, pain, shame, and
      unattractiveness were significantly scored higher in the nonoperated group.
      Subjective esthetic score was significantly higher in the operated group (2.5 vs.
      7.1). The data of this study provide further evidence that women who have been
      operated for breast hypertrophy have a significant improvement in quality of life
      compared with those who are not yet operated. These data are further evidence
      that breast hypertrophy is not solely an esthetic problem.

PMID- 16106158
TI  - Immediate bilateral breast reconstruction with implants and inferolateral
      AlloDerm slings.
AB  - To shorten the reconstructive process, improve results, and provide additional
      options for women seeking mastectomy, we used an acellular cryopreserved dermal
      matrix (AlloDerm) sling to reestablish the lower pole of the pectoralis major
      muscle. This technique creates a subpectoral-sub-AlloDerm pocket that completely
      encloses the breast implant. By tailoring the width of the AlloDerm, we can
      precisely control the degree of lower-pole fullness. This technique shortens or
      eliminates the need for tissue expansion and provides an additional option for
      single-stage breast reconstruction with implants. We have selectively used this
      technique as a reconstructive option for 10 women undergoing bilateral mastectomy
      (20 breasts).

PMID- 16106159
TI  - Nipple-areola complex preservation: predictive factors of neoplastic nipple
      areola complex invasion.
AB  - Recently, skin-sparing mastectomy (SSM) with nipple-areola complex (NAC)
      preservation has been promoted as an oncologically safe procedure in practice for
      selected patients. The criteria of selection have not been yet defined precisely.
      The focus of this study was to investigate predictive factors of NAC-base
      neoplastic involvement to define the indications for NAC preservation. A
      prospective clinical study was conducted of 108 randomly selected female patients
      with invasive breast cancer. Analyzed markers of NAC involvement were tumor
      nipple distance (TND), tumor size, localization, histologic type, grade,
      lymphovascular invasion (LVI), site, and axillary lymph-node status. The
      definitive histologic findings of the NAC base were compared with analyzed
      markers and the frozen section results. NAC base was positive in 23.15% patients
      at definitive histology with false-negative results in 4.63% patients at
      intraoperative frozen section. Significant differences were found in TND, tumor
      size, axillary lymph-node status, and LVI. There were no significant differences
      in tumor grade and site and not enough cases for statistical evaluation in
      histologic type and localization. Clinical indications for NAC preservation,
      according to this study, include tumors < or =2.5 cm, TND >4 cm, negative
      axillary lymph node status, and no LVI. Considering the possibility of pre- or
      intraoperative measurement, tumor size, and TND evaluation will result in the
      lowest possible mistakes in NAC preservation. Frozen section analyses of the NAC
      base, because of the "false-negative" possibility, could be deemed as a relative
      prognostic factor until definitive histologic findings. The presence of an
      extensive intraductal component (EIC) in the "borderline" cases of these criteria
      could be an additional argument for NAC removal.

PMID- 16106160
TI  - Avoiding free nipple grafting with the inferior pedicle technique.
AB  - In cases of severe macromastia, the free nipple graft technique has been the
      traditional alternative to pedicle transposition. Distress over nipple survival
      in large reduction mammaplasty and long pedicle transposition is largely
      responsible for this.A retrospective investigation of the records of 142
      reduction mammaplasty patients was carried out to determine whether nipple
      survival or overall complication rates were significantly different in patients
      undergoing larger (>1500 g per side) as compared with smaller reductions (< 1500
      g per side). The 2 patient groups were compared with respect to mild or severe
      complications. Data were analyzed using Fisher exact test and 2-sample t tests. A
      P value of < 0.05 was considered statistically significant. No patient in either
      group had total nipple loss. There were no statistically significant differences
      in major or minor complications between the 2 groups. In our experience, the
      inferior pedicle, Wise pattern reduction is a reliable and predictable method of
      reduction, appropriate for all breast sizes and pedicle lengths.

PMID- 16106161
TI  - Immediate breast reconstruction and high-dose chemotherapy.
AB  - BACKGROUND: Immediate breast reconstruction (IBR) is considered as a safe
      procedure nowadays, and it can be proposed in the majority of patients requiring
      a mastectomy. In fact, recent studies have demonstrated that immediate breast
      reconstruction is not detrimental also to patients with locally advanced breast
      cancers. However, IBR should be reevaluated in case of locally advanced breast
      cancer requiring high-dose chemotherapy (HDCT). The aim of this study is to
      evaluate both the risk of chemotherapy delay due to surgical complications and
      the risk of late surgical complications related to the association with HDCT. We
      considered 3 series of 23, 67, and 15 patients requiring a mastectomy at the
      European Institute of Oncology in Milan. After mastectomy, these groups
      respectively received an IBR and HDCT, an IBR and conventional chemotherapy, and
      only HDCT with no IBR. METHODS: Files of 105 patients who were admitted to our
      department from October 1999 to January 2002 were reviewed. Twenty-three patients
      underwent a mastectomy, followed by IBR and HDCT; 67 underwent a mastectomy plus
      IBR plus conventional CT; and, finally, 15 underwent a mastectomy alone followed
      by HDCT. The reconstructive techniques performed were 72 permanent prosthesis and
      18 temporary expanders. We excluded all patients with IBR by flap (latissimus
      dorsi or pedicled rectus abdominis) to improve the homogeneity of the sample.
      RESULTS: All patients who underwent IBR started high-dose chemotherapy without
      any delay; the time elapsed between surgery and HDCT is not significantly
      different for patients with and without IBR (54 versus 60 days, P = 0.13). The
      early complication rate (before CT) was 2.9% (2 patients with infection). The
      late complication rate (after CT) was higher for the group that underwent IBR
      followed by HDCT (39% versus 20%). CONCLUSION: We did not observe any delay for
      the administration of high-dose chemotherapy after mastectomy with IBR surgery.
      The complication rate before HDCT is similar to the complication rates published
      in the literature. On the contrary, we observed a higher rate of infections (13%
      versus 0%, P = 0,014) after HDCT than after conventional CT, which can be related
      to the association with high-dose chemotherapy, inducing a decrease of the immune
      defenses. These results seems to demonstrate that the association of IBR with
      HDCT is not detrimental to patients from the oncological point of view, but the
      impact of HDCT on the reconstruction is more negative. Further studies are needed
      to verify if this risk exists, although lower, in the association with
      conventional CT. However, a careful evaluation of the risk of infections should
      be considered preoperatively, and perioperative contaminations should be
      carefully prevented.

PMID- 16106162
TI  - On the neglected entity of unilateral gynecomastia.
AB  - Although there are many articles in the literature on the etiology,
      classification, and management of gynecomastia, the entity of unilateral
      gynecomastia has not received much attention. In this article, 15 consecutive
      males (seen over a 10-year period) with unilateral gynecomastia were
      retrospectively reviewed. The study showed the unique presentation in this group
      of patients. One third of the patients (n = 5) had "cancer phobia" and were
      worried either because of the presence of a mass (n = 2) or because of the
      unilaterality of their disease (n = 3). The study also showed the predominance of
      true (glandular) gynecomastia, and this has also been observed in other cases of
      unilateral involvement in the literature. All patients underwent preoperative
      mammography. Mammographic findings were consistent with gynecomastia in all
      patients, including the 2 patients with concurrent breast masses. All patients
      underwent subcutaneous mastectomy, and histologic examination confirmed the
      diagnosis. Finally, the literature on unilateral gynecomastia was reviewed.

PMID- 16106163
TI  - Levobupivacaine versus ropivacaine infiltration analgesia for mastopexy: a
      comparative study of 2 long-acting anesthetic drugs in infiltrative anesthesia
      for mastopexy.
AB  - A prospective double-blind study was conducted to compare the analgesic
      properties of levobupivacaine and ropivacaine in a bilaterally symmetrical
      mastopexy model. Both of these 2 long-acting local anesthetic amides are
      associated with lower cardiac and central nervous system toxicity than racemic
      bupivacaine, a widely used agent for long-lasting perioperative analgesia in
      esthetic procedures. In this study, each of the 18 patients undergoing bilateral
      mastopexy under conscious sedation received preoperative infiltration with
      levobupivacaine in 1 breast and equal volume of ropivacaine in the other.
      Patients were requested to assess their pain separately in each side every 2
      hours and for 12 hours postoperatively on a visual analog scale. Overall
      analgesia achieved up to 12 hours postoperatively was found to be statistically
      different between the 2 local anesthetic factors in favor of levobupivacaine. At
      2 hours postoperatively, no difference was found between the 2 local anesthetic
      agents in terms of analgesic efficacy (P = 0.298). However, postoperative pain
      scores recorded after infiltration with levobupivacaine were significantly lower
      than pain scores for the ropivacaine-infiltrated sides (P<0.001) at all other
      timeframes. Both anesthetics provided satisfactory analgesia for at least 10
      hours, but constantly low pain scores were recorded for levobupivacaine for 10
      hours postoperatively, whereas for ropivacaine only for 6 hours. At 12 hours, 66%
      of patients needed oral analgesia for pain in the ropivacaine-infiltrated breast.
      It is concluded that levobupivacaine is more effective for local infiltrative
      analgesia in mastopexy than ropivacaine, providing longer-lasting postoperative
      analgesia.

PMID- 16106164
TI  - Common risk factors seen in secondary carpal tunnel surgery.
AB  - BACKGROUND: We hypothesized that there are several common risk factors associated
      with secondary carpal tunnel releases. Therefore, we chose to investigate these
      common factors by analyzing the charts of those patients requiring a second
      carpal tunnel release (CTR) procedure. METHODS: A retrospective chart review was
      performed, and patients were identified by searching hospital medical record
      databases using the Common Procedural Terminology. RESULTS: Between January 1,
      2000, and March 31, 2004, 2357 patients had a primary CTR, and 48 of them were
      found to have had a secondary CTR (of these 48, 9 had diabetes mellitus, 11 had
      hypertension, and 6 had gastrointestinal-related illnesses). Seven percent of
      those who had an open release primarily required a second CTR, while only 0.2% of
      those who had an endoscopic release primarily required a second CTR. CONCLUSION:
      A greater number of secondary CTR procedures were required for those patients
      with symptoms of carpal tunnel syndrome in the group that had an open release
      primarily versus those that had an endoscopic release primarily. Diabetes
      mellitus and hypertension may also contribute to the need for secondary surgery.

PMID- 16106165
TI  - Tenolysis after combined digital injuries in zone II.
AB  - A retrospective review of 23 patients with restricted motion after 32 combined
      digital injuries or amputations in zone II treated with tenolysis was conducted
      at an average follow-up of 5 years. Significant functional improvement was
      achieved in 28 out of 32 digits (88%). Total active motion improved on average 51
      degrees after dorsal tenolysis, 55 degrees after palmar tenolysis, and 63 degrees
      after combined dorsopalmar tenolysis. Using the Buck-Gramcko scoring system, 15
      digits reached excellent results, 8 showed a good result, 4 had a fair result,
      and 5 were rated as poor. No digits were lost. All patients returned to a full
      time job. Complications consisted of 16% flexor tendon ruptures after palmar or
      combined tenolyses. In contrast, dorsal tenolysis proved to be a safe procedure.
      Prerequisites for success are compliant patients who are willing to undergo
      therapy for at least 3 months postoperatively. Despite the demanding
      postoperative therapy, the individual patient satisfaction is high following
      tenolysis.

PMID- 16106166
TI  - Subungual exostosis: a review of 16 cases focusing on postoperative deformity of
      the nail.
AB  - We reviewed the clinical features of 16 patients who underwent surgery for
      subungual exostosis, focusing on postoperative deformity of the nail. In 7
      patients, the lesion did not destroy the nail bed and was excised with a fish
      mouth-type incision. In 9 patients, the lesion destroyed the nail bed and was
      excised with a direct approach. In 5 of the 9 patients, artificial skin was
      applied after excision of the tumor because the defect of the nail bed was large.
      Good postoperative appearance of the nail was obtained by a fish-mouth-type
      incision when the tumor did not destroy the nail bed, although 2 patients had
      local recurrence. Onycholysis occurred postoperatively when the tumor destroyed
      the nail bed and the defect of the nail bed was large after excision of the
      tumor. Secondary nail bed reconstruction may be indicated in such cases with
      postoperative deformity of the nail.

PMID- 16106167
TI  - Treatment of congenital melanocytic naevi with CO2 laser.
AB  - This study assesses the effectiveness of CO2 laser in treating congenital
      melanocytic naevi (CMN). A retrospective review of 12 patients with CMN treated
      with CO2 laser was carried out. In all cases, there was minimal visible naevus
      after treatment. Six patients developed hypertrophic scarring; this was
      significantly more likely following CO2 laser treatment on the anterior torso,
      flanks, or arms than on the back or buttocks (P = 0.01, 1-tailed Fisher exact
      test). We conclude that CO2 laser is an effective treatment for reducing visible
      pigmentation of CMN. However, it can cause hypertrophic scarring, which has not
      been reported before. This risk can be reduced by limited use in areas of the
      body where the dermis is thinner or there is a known risk of hypertrophic
      scarring. In addition, the cautious use of paint mode and prophylactic use of
      pressure or silicon dressings may also reduce the risk of hypertrophic scarring.

PMID- 16106168
TI  - End-to-side nerve coaptation: is an additional proximal coaptation useful when
      available?
AB  - The aim of this experimental study was to evaluate the effects of end-to-side
      coaptation of the proximal end of a severed nerve to the same intact nerve, in
      addition to traditional end-to-side coaptation of the distal end, with an aim to
      use the intact nerve as a nerve conduit in a rat model and to compare the
      functional and histologic results of this modality to those obtained after nerve
      grafting and traditional end-to-side nerve coaptation. In group A, a peroneal
      nerve defect measuring 1 cm was created in the left hind limb, and a nerve graft
      1 cm long was used to bridge the defect. In group B, only the distal stump of the
      peroneal nerve was coapted to the intact tibial nerve. In group C, both ends of
      the peroneal nerve defect were coapted to the intact tibial nerve in an end-to
      side fashion 1.5 cm apart from each other, and in group D, the peroneal nerve
      defect was left unrepaired. Group E was consisted of nonoperated peroneal nerves
      that were used to obtain normative data. Although significantly higher myelinated
      axon densities were observed in groups B and C compared with group A and group E,
      total number of the myelinated axons was significantly higher only in group C.
      Peroneal functional index assessments demonstrated that nerve recovery in the
      peroneal nerve was similar in groups A and C, and both were better than those
      observed in groups B and D. Collectively, these results suggest that end-to-side
      coaptation of both ends of a severed nerve to an intact nerve, in case of a nerve
      defect in this length, may serve as an alternative for nerve grafting.

PMID- 16106169
TI  - Open guide suture technique for safe microvascular anastomosis.
AB  - Despite the evident advances in microsurgery, anastomosis of small vessels or
      anastomosis of vessels having size discrepancy, remains one of the most precise
      and technically demanding issues in replantation surgery and free tissue transfer
      procedure. The patency of the vascular anastomosis is critical and essential for
      a successful outcome. In this study, a microvascular anastomosing technique
      called open guide suture technique is introduced. The technique starts with a
      conventional whole-layer stitch and continues under the control of a guided
      suture that is inserted but not completed to a knot 180 degrees distant from the
      initial suture. Recently, we used this technique in 30 free flap transfers and 4
      replantation procedures. A total of 103 anastomoses were performed. Only 1 flap,
      which had both arterial and venous problems, and 1 finger replantation case that
      had arterial problems required revision. Both the revised cases were salvaged,
      giving a revision rate of 2.91% for the total number of anastomoses (3 of 103),
      and a 100% success rate for final flap and replanted part survival. In
      conclusion, this technique provides a safe anastomosis performed under completely
      clear visualization at each step with well-arranged knot intervals.

PMID- 16106170
TI  - Improved flap viability with site-specific delivery of sildenafil citrate using
      fibrin glue.
AB  - Sildenafil is a cyclic guanosine-specific phosphodiesterase type 5 (PD-5)
      inhibitor that is widely used for erectile dysfunction. Potent and competitive
      inhibition of PD-5 enhances levels of cyclic guanosine monophosphate (cGMP).
      Fibrin glue-apart from tissue fixation-has been used for slow release of drugs.
      In this study, local delivery of Sildenafil citrate with fibrin glue was
      accomplished to improve random flap survival. Fifty Wistar rats were randomized
      into 5 groups, and a standardized dorsal random-pattern skin flap was elevated in
      each rat. In Group I (n = 10), the base of the flap was divided, making it a
      "graft" control to study the graft effect. In Group II (n = 10), a thin Silastic
      sheet was used to separate the flap from the underlying vascular bed, and no
      pharmacologic treatment was given. In Group III (n = 10), only 0.5 mL of fibrin
      glue was applied to the flap donor site. In Group IV (n = 10), 2.5 mg of
      sildenafil citrate mixed in 0.5 mL of fibrin glue was applied to donor site of
      the flap, whereas 10 mg of sildenafil citrate mixed in 0.5 mL of fibrin glue was
      applied in Group V (n = 10). Area of flap survival was evaluated on postoperative
      seventh day. Total necrosis of all of the flaps was observed in "graft" control
      group (Group I). Sildenafil and fibrin glue groups (Group IV and V) resulted in a
      statistically significant decrease in flap necrosis compared with Groups II and
      III (P < 0.0001). A statistically significant difference could not be documented
      between Group II and Group III (P > 0.0001). The decrease in skin necrosis was
      statistically significant in Group V compared with Group IV (P < 0.0001).
      Histologic examination revealed significantly increased vascular density in
      Groups IV and V compared with Groups II and III (P < 0.0001), whereas a
      significant difference could not be documented between Groups IV and V (P >
      0.0001) and between Groups II and III (P > 0.0001). In view of these results,
      topical sildenafil application seems to improve flap survival in random-pattern
      skin flaps in dose-dependent manner.

PMID- 16106171
TI  - New surgical approach in facial transplantation extends survival of allograft
      recipients.
AB  - We have previously developed a composite total face-scalp allotransplantation
      model based on bilateral common carotid arteries (CCA) and external jugular
      veins. To decrease the mortality rates, different modifications of arterial
      anastomoses in the facial allograft recipients are presented. Eighteen full face
      scalp allograft transplantations were performed across major histocompatibility
      (MHC) barriers between ACI (RT1) donors and Lewis (RT1) recipients. Bilateral CCA
      and bilateral external carotid arteries of the recipients were used as recipient
      vessels to vascularize the flap in 5 and 4 transplants, respectively. In 9
      transplants, unilateral CCA of the recipients were used to vascularize the
      face/scalp flap. All the animals received CsA 16 mg/kg/d Sc, which was tapered
      over 4 weeks to 2 mg/kg/d. In transplants utilizing bilateral CCA, the survival
      rate of the animals was very short. Transplants in which unilateral CCA were used
      yielded 100% survivals over 200 days posttransplant. These modifications of
      arterial anastomoses have significantly improved survival of facial allograft
      recipients.

PMID- 16106172
TI  - Improving long-term projection in nipple reconstruction using human acellular
      dermal matrix: an animal model.
AB  - Reconstructed nipples rapidly lose projection. We describe the use of human
      acellular dermal matrix (ADM) to improve long-term projection of nipple flaps.
      Athymic rats were randomized to 3 groups; each received 2 nipples: bell flap
      (control, n = 16 nipples), bell flap with a cylinder of implanted ADM (n = 24),
      or bell flap with intraflap injection of micronized ADM (MADM) (n = 10). Seven of
      24 ADM nipples extruded (30%). By 12 weeks, the control nipples maintained 44% of
      initial projection compared with 70% for ADM nipples (P = 0.000025). The MADM
      nipples maintained 49% of initial projection after 12 weeks (P = 0.55 compared
      with control). No MADM nipples extruded. ADM grafts maintain long-term projection
      better than local tissue flaps alone. We hypothesize that MADM may limit
      extrusion and allow for serial injection of nipples. Based on the promising
      results of this study, clinical trials are warranted using human ADM and/or human
      MADM for nipple reconstruction.

PMID- 16106173
TI  - Combined semimembranosus muscle and epigastric skin flap: a new model of
      composite-free flap in the rat.
AB  - We present a new model of combined semimembranosus muscle and epigastric skin
      free flap based on a single pedicle consisting of the muscular branch of
      semimembranosus muscle and superficial epigastric vessels in continuity with
      femoral vessels. In 10 rats, the anatomy of the semimembranosus muscle was
      studied in detail. The mean length of the muscle was 38 mm and width was 11 mm.
      The mean weight of the muscle was 1.03 g. The mean external diameter of the
      femoral artery was 1 mm and vein was 1.2 mm. Eight combined
      semimembranosus/epigastric skin flaps were dissected and transferred into the
      neck and contralateral groin regions with 100% success rate. This model of
      combined muscle and skin flap has several advantages. It is reliable, versatile,
      easy to dissect with long vascular pedicle and adequate vessel diameter for the
      anastomoses. It can be used for different applicability, including
      microcirculatory, pharmacologic, physiological, biochemical, and immunologic
      studies.

PMID- 16106174
TI  - Identification of P-cadherin in primary melanoma using a tissue microarrayer:
      prognostic implications in a patient cohort with long-term follow up.
AB  - Sentinel lymph node biopsy is the most accurate technique for establishing
      melanoma patient prognosis but is associated with morbidity and is of little
      value in those tumors that first metastasize to sites other than the regional
      nodal basin. Noninvasive methods of establishing prognosis are therefore
      desirable. We have used the novel technology of tissue microarray to study a
      cohort of 120 patients with melanoma with long-term follow-up data for the
      expression of P-cadherin. The tissue microarray was successfully constructed and
      stained. Loss of P-cadherin expression was found to be significantly correlated
      with outcome (log rank chi2 = 10.1336, P = 0.0015). The results suggest a
      fundamental role for P-cadherin in melanoma progression and identify it as a
      potential prognostic marker and a possible target for therapeutic manipulation.

PMID- 16106175
TI  - The true triplication of the thumb: a case of unclassified thumb polydactyly.
AB  - A child with true triplication of the thumb is reported. Each thumb has a well
      developed metacarpal, and one of them is biphalangeal; the remaining 2 are
      triphalangeal. Satisfactory result was obtained from a functional and esthetic
      point of view. Our surgical approach to this interesting anomaly and the
      necessity of a new group under the Wassel classification for the categorization
      of different forms of thumb triplications is discussed.

PMID- 16106176
TI  - Invited discussion: the true triplication of the thumb: a case of unclassified
      thumb polydactyly.

PMID- 16106177
TI  - Intussusception of a transferred jejunal flap in cervical esophagus
      reconstruction.
AB  - Although jejunal flaps have been used frequently for esophageal reconstruction,
      and the techniques for transfer, as well as subsequent modification, have been
      well described, a variety of complications still poses problems for both
      physicians and patients. The challenge exists in avoidance and management of
      complications. The purpose of this report is to present an unusual but severe
      complication involving a jejunal flap that was transferred to the neck for
      esophageal reconstruction. Intussusception of the jejunal flap occurred 1 year
      after flap transfer due to redundancy of the transferred segment. The patient was
      a child who had esophageal reconstruction for severe dysphagia that was due to a
      previous history of radiation injury. The disorder was successfully treated
      surgically with manual reduction of the intussuscepted segment, followed by
      shortening of the jejunal flap to prevent future recurrence. One should keep in
      mind that redundancy of the reconstructed esophagus may cause dysphagia due to
      kinking or, in this case, intussusception, which may result in necrosis of a
      segment of the transferred jejunum. One of the measures that should be taken
      during the initial reconstruction to prevent these serious complications is to
      perform the final inset of the jejunal flap after revascularization. This allows
      for proper assessment of jejunal length, which undergoes a significant change
      after restoration of the vascular supply.

PMID- 16106178
TI  - Abdominal wall neuroma pain after breast reconstruction with a transverse
      abdominal musculocutaneous flap: cause and treatment.
AB  - Breast reconstruction with either a pedicled or microvascular transfer of the
      transverse rectus abdominus musculocutaneous flap, whether with or without the
      muscle, is now the standard of care when patients choose an autologous form of
      reconstruction. Complications related to flap loss and abdominal wall weakness
      have been well described. Complications related to painful neuromas of the
      intercostal nerves, ilioinguinal and iliohypogastric nerves have not been
      described previously. The diagnosis and treatment of pain related to neuromas of
      the abdominal wall is discussed in this paper.

PMID- 16106179
TI  - Condylar positioning in sagittal split ramus osteotomy by the triangle method.
AB  - BACKGROUND: Several methods for maintaining the preoperative condyle position
      after mandibular ramus surgery have been suggested. But when applied, those have
      been proven to be uncomfortable and less practical; hence, maintaining
      preoperative condyle position has mainly relied on the operator's personal
      experience. PATIENTS AND METHOD: We developed a new technique on the basis of the
      triangle's principle (namely the triangle method) for positioning of the condyle
      and applied it to 72 patients with sagittal split ramus osteotomy. We followed
      them for an average of 24.4 months. RESULTS: None of the patients who were
      operated on using the triangle method had postoperative temporomandibular joint
      problems or relapses related to inappropriate temporomandibular joint position.
      CONCLUSION: The triangle method for condylar positioning in the mandibular ramus
      osteotomy is a simple, reliable, cheap, and easy-to-learn tool for condylar
      positioning.

PMID- 16106180
TI  - Extended deepithelialization to secure double-breasted closure of the skin.
AB  - Double-breasted closure of the skin is achieved by deepithelialization of 1 edge
      of a wound and advancement of the opposite edge over this deepithelialized area.
      Such closure may prevent contamination or exposure of the implant in cases where
      immediate breast reconstruction with prosthetic material is obtained after skin
      sparing mastectomy. The deepithelialization routinely extends as far as the
      incision to be closed and, consequently, the skin suture at the end of the
      incision immediately overlies thedeep suture or implant in cases where the
      implant is not fully covered by muscle. To prevent contamination or exposure of
      the implant when suture infection or wound dehiscence occurs in these cases, we
      extend the deepithelialization beyond and around the limit of the skin incision.
      This allows for complete and secured double-breasted closure of the entire wound
      and lessens the risk of implant contamination or exposure.

PMID- 16106181
TI  - Sandra's day.

PMID- 16106182
TI  - Anomalous origin of the left main coronary artery from the right sinus of
      Valsalva with an intramural course identified by transesophageal echocardiography
      in a 14 year old with acute myocardial infarction.
AB  - Coronary artery anomalies have an incidence of 0.6% to 1.3% in angiographic
      studies and 0.3% in an autopsy series. Anomalous origin of the left main coronary
      artery (LMCA) from the right sinus of Valsalva (RSOV) represents a small fraction
      (1.3%) of these anomalies, with an overall prevalence of 0.017% to 0.03% in
      angiographic studies. The high incidence of sudden cardiac death associated with
      this specific anomaly during or immediately after vigorous physical exercise
      makes identification and appropriate surgical intervention critical. We present a
      case report of a 14-year-old patient with an LMCA arising from the RSOV with an
      initial intramural course, presenting with acute myocardial infarction (AMI) as
      the first indication of the anomaly. Transthoracic echocardiogram suggested this
      anomaly, which was confirmed by cardiac catheterization and transesophageal
      echocardiogram.

PMID- 16106183
TI  - Diabetes and stress hyperglycemia associated with myocardial infarctions at an
      urban municipal hospital: prevalence and effect on mortality.
AB  - Municipal hospitals in large cities provide care for patients from immigrant and
      mixed ethnic communities that are at high risk for diabetes. Both diabetes and
      stress hyperglycemia increase the risk of adverse outcome after myocardial
      infarctions, and the impact of stress hyperglycemia on the outcome of myocardial
      infarctions in this particular setting has not been previously studied. We
      therefore undertook a retrospective cohort study to determine the prevalence of
      diabetes and stress hyperglycemia in patients presenting to a university
      affiliated Bronx municipal hospital with myocardial infarction, and the
      relationship of these conditions to the extent of coronary disease and mortality.
      We obtained data on 106 consecutive patients from July 1998 to April 1999 with a
      diagnosis-related group diagnosis of either myocardial infarction or acute
      coronary syndrome, in which myocardial infarction was confirmed by serum enzymes
      or characteristic electrocardiographic changes. Patients were followed until
      March 30, 2001. Measurements of clinical parameters and results of
      catheterization were obtained for all patients. Death rates were determined by
      laboratory database, direct patient contact, or data from National Death Index.
      Eighty percent of the cohort had either a diagnosis of diabetes (n = 45, 42% of
      cohort) or evidence of stress hyperglycemia (defined as serum glucose greater
      than 126 mg/dL at the time of admission without prior diagnosis of diabetes, n =
      40, 38%). In-hospital mortality for patients with diabetes, stress hyperglycemia,
      or normal glucose was 20%, 15%, and 14%, respectively. Eighty-three percent of
      the cohort received beta blockers, and 61% of hospital survivors had
      catheterization. Left main or triple vessel disease was common in both patients
      with diabetes (52%) and patients with stress hyperglycemia (32%). Mortality at
      follow up (maximum follow up 3 years; mean follow up 19.6 months) was much higher
      in patients with either diabetes (42%) or stress hyperglycemia (52%) than normal
      subjects (24%). Kaplan-Meier analysis of the difference in mortality between
      patients with high glucose on admission and normal subjects was borderline
      significant (P = 0.06). Multivariate regression demonstrated that age (P =
      0.020), increase in admission serum creatinine (P = 0.001), and reduction in
      either ejection fraction (P = 0.016) or admission systolic blood pressure (P =
      0.005) were significant predictors of mortality. Glycemic status and sex were not
      independently associated with death after controlling for these other factors.
      These results show that the prevalence of both diabetes and stress hyperglycemia
      on presentation with myocardial infarction is strikingly high in this immigrant,
      mixed ethnic, urban population. Patients with diabetes and stress hyperglycemia
      had advanced disease on presentation and much higher mortality at 2 to 3 years
      than those with normal blood glucose. The mortality difference is the result of
      older age and more advanced disease rather than hyperglycemia per se.

PMID- 16106184
TI  - Heart failure disease management: implementation and outcomes.
AB  - Millions of dollars are being spent to identify new therapies to improve
      mortality and morbidity for the growing epidemic of patients sustaining heart
      failure. However, in clinical practice, these therapies are currently underused.
      To bridge the gap between proven therapies and clinical practice, the medical
      community has turned to disease management. Heart failure disease management
      interventions vary from vital-sign monitoring to multidisciplinary approaches
      involving a pharmacist, nutritionist, nurse practitioner, and physician. This
      review attempts to categorize these inventions based on location. We compared the
      published results from randomized, controlled trials of the following types of
      heart failure disease management interventions: inpatient, clinic visits, home
      visits, and telephone follow up. Although research shows an improvement in the
      quality of care and a decrease in hospitalizations for patients sustaining heart
      failure, the economic impact of disease management is still unclear. The current
      reimbursement structure is a disincentive to providers wanting to offer disease
      management services to patients sustaining heart failure. Additionally, the cost
      of providing disease management services such as additional clinical visits,
      patient education materials, or additional personnel time has not been well
      documented. Most heart failure disease management studies do confirm the concept
      that providing increased access to healthcare providers for an at-risk group of
      patients sustaining heart failure does improve outcomes. However, a large-scale
      randomized, controlled clinical trial based in the United States is needed to
      prove that this concept can be implemented beyond a single center and to
      determine how much it will cost patients, providers, healthcare systems, and
      payers.

PMID- 16106185
TI  - Peroxisome proliferator-activated receptor-alpha and atherosclerosis: from basic
      mechanisms to clinical implications.
AB  - Atherosclerosis is an inflammatory process, triggered by the presence of lipids
      in the vascular wall, and encompasses a complex interaction among inflammatory
      cells, vascular elements, and lipoproteins through expression of several adhesion
      molecules and cytokines. Activation of the nuclear receptor, peroxisome
      proliferator-activated receptor-alpha (PPAR-alpha), has been demonstrated to
      modulate many aspects of lipoprotein metabolism and inflammation in vitro as well
      as in animal and human studies. The tissue distribution of PPAR-alpha is
      extensive, and it is abundantly present in the vascular wall where it may mediate
      many of antiinflammatory and antiatherogenic effects. Major clinical trials such
      as the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT), the
      Helsinki Heart Study, and the Diabetes Atherosclerosis Intervention Study (DAIS)
      have demonstrated the beneficial effects of synthetic agonists of PPAR-alpha,
      specifically fibric acid derivatives, on cardiovascular disease outcome. Although
      fibric acid trials have reported cardiovascular risk reduction in patients with
      dyslipidemia, the favorable alterations in plasma lipids can only partially
      explain the reduction in cardiovascular events in these studies. One common link
      among these trials was a cohort with a high prevalence of insulin resistance or
      diabetes, conditions associated with heightened systemic inflammation and
      increased risk for development and progression of atherosclerosis. We review the
      many antiatherogenic effects of PPAR-alpha ligands and evidence from fibric acid
      trials that individuals with insulin resistance or diabetes benefit the most from
      these drugs, consistent with their antiinflammatory and antithrombotic
      properties.

PMID- 16106186
TI  - Nonpharmacologic approaches for the treatment of hyperlipidemia.
AB  - Coronary heart disease (CHD) is the leading cause of death in the United States.
      Dyslipidemias, like decreased high-density lipoprotein (HDL) and increased low
      density lipoprotein (LDL), have been linked through epidemiologic and
      experimental studies with the development of atherosclerosis and an increased
      risk of CHD. The introduction of various classes of lipid-lowering drugs,
      especially the hydroxymethylglutaryl-coenzyme-A-reductase inhibitors (statins),
      has allowed for effective treatment of hyperlipidemia. This article reviews the
      following nonpharmacologic approaches to hyperlipidemia: LDL apheresis, surgery,
      the emergence of HDL as a therapeutic target, gene therapy, and finally, the
      possibility of developing a vaccine against atherosclerosis.

PMID- 16106187
TI  - Sarcoidosis masquerading as an acute coronary syndrome.
AB  - Sarcoidosis is a common multisystem granulomatous disease that affects 20 per
      100,000 people in the world. Although primarily a pulmonary disease, sarcoidosis
      can affect multiple organ systems. Cardiac involvement of sarcoidosis is most
      commonly manifested as ventricular ectopy and arrhythmias; atrioventricular
      conduction disturbances, including complete heart block; congestive heart
      failure; and even may result in sudden death. Although myocardial infarction is
      most commonly the result of epicardial coronary artery disease, an infiltrative
      process such as sarcoidosis may simulate an acute coronary syndrome. Given the
      high prevalence of sarcoidosis, it is important to be aware of the myriad of
      cardiac manifestations of this infiltrative process.

PMID- 16106188
TI  - Left main dissection and thrombosis in a young athlete.
AB  - Spontaneous coronary artery dissection is a rare but morbid event. We present the
      case of a previously healthy 38-year-old man who experienced severe chest
      discomfort while vigorously exercising. An acute anterolateral myocardial
      infarction was diagnosed. The patient underwent coronary angiography,
      demonstrating acute thrombosis of the left main coronary artery. The patient was
      referred for immediate bypass surgery. Examination of the left main coronary
      artery in the operating room revealed a dissection flap with thrombosis. With
      successful surgical intervention, the patient made an uneventful recovery. This
      case is discussed and the literature reviewed.

PMID- 16106189
TI  - Single coronary artery, ventricular tachycardia, and a family history of sudden
      death.
AB  - A single coronary artery was found in a 55-year-old woman undergoing coronary
      angiography. The left coronary had a normal distribution, with the right coronary
      originating as a continuation of the distal left circumflex (L-I subtype). The
      patient had a 5-month history of chest pains of short duration accompanied by a
      feeling of tachycardia. During childhood, the patient experienced frequent
      episodes of syncope. The patient's brother died suddenly of an unknown cause,
      presumably cardiac, at the age of 42. Because of an episode of nonsustained
      ventricular tachycardia during an ergometer exercise test, the patient underwent
      a comprehensive program of diagnostic procedures but no other abnormalities were
      demonstrated. A cardioverter defibrillator was implanted.

PMID- 16106190
TI  - Glucose-insulin-potassium therapy in the era of coronary revascularization.
AB  - Glucose-insulin-potassium (GIK) utilization in the treatment of acute myocardial
      infarction (AMI) has been studied since the early 1960s with varying results. It
      is well established that ischemic myocardial cells convert from aerobic
      metabolism of glucose to toxic anaerobic free fatty acid (FFA) metabolism for the
      production of energy. It has been hypothesized that administration of GIK during
      coronary revascularization would decrease the degree of myocardial damage.
      Earlier clinical trials, before the revascularization era, demonstrated a
      potential role for GIK therapy to reduce the mortality and morbidity associated
      with AMI. In recent years, GIK therapy has been incorporated into current
      revascularization methods without clear evidence as to its efficacy. Based on the
      most current studies, it has been determined that GIK therapy is not beneficial
      in patients with AMI, regardless of revascularization status, and therefore
      should not be used.

PMID- 16106191
TI  - Tissue processing re-visited: a shifting paradigm in surgical pathology.

PMID- 16106192
TI  - Methodology for preservation of high molecular-weight RNA in paraffin-embedded
      tissue: application for laser-capture microdissection.
AB  - Laser-capture microdissection techniques have enhanced the ability to perform
      molecular studies of pure-cell populations. Although many technical factors
      affect the outcome of the procedure, none is more critical than the appropriate
      handling of the tissue. Because extraction of intact RNA from paraffin-embedded
      tissue is a difficult and inconsistent process, frozen sections with their
      attendant problems are used for this purpose. The major limitation of frozen
      section is its inferior morphologic quality compared with paraffin-embedded
      sections that may complicate accurate identification of cells during
      microdissection. We have developed a procedure that provides both high-quality
      histomorphology and RNA preservation in paraffin-embedded tissue. It is based on
      the use of a methanol-based fixative coupled with microwave-assisted rapid tissue
      processing. This technology in conjunction with a modified hematoxylin-eosin
      stain and a RNA extraction method allows isolation of high molecular-weight RNA
      from laser-capture microdissected, hematoxylin and eosin-stained paraffin
      sections. The high quality of the extracted RNA was confirmed by capillary
      electrophoresis and RT-PCR. The combination of a methanol-based fixative, rapid
      microwave tissue processing, and a modified hematoxylin and eosin stain produces
      paraffin sections that yield high molecular-weight RNA upon microdissection. This
      methodology opens the door for a wide range of gene expression analyses using
      paraffin-embedded tissue.

PMID- 16106193
TI  - Mutational analysis of the c-KIT AND PDGFRalpha in a series of molecularly well
      characterized synovial sarcomas.
AB  - The c-KIT and the platelet-derived growth factor receptor alpha (PDGFRalpha) have
      been shown to be important for tumor growth and progression in several soft
      tissue sarcomas, including synovial sarcomas (SSs). It has been suggested that
      these c-KIT-positive cases might benefit from a tyrosine kinase inhibitor
      therapy. In this study, we analyze a series of SSs to investigate the presence of
      c-KIT and PDGFRalpha mutations with the aim of selecting those for a more
      adequate and appropriate therapy. We analyzed fresh-frozen tissues from 12 SSs (8
      primary tumors and 4 nude mice xenotransplants from primary tumors). RNA was
      extracted to identify the presence of the SYT-SSX gene fusion to confirm the SS
      diagnosis. Mutational analysis of exons 9, 11, 13, and 17 of c-KIT and exons 12
      and 18 of PDGFRalpha was performed by direct sequencing. Immunohistochemical
      analysis of c-KIT, PDGFRalpha, and p-PDGFRalpha was also performed. All analyzed
      cases showed the presence of SYT-SSX gene fusion transcripts confirming the
      diagnosis of SS, 10 carried the SYT-SSX1 fusion, and 2 the SYT-SSX2.
      Immunohistochemical analysis showed expression of c-KIT in 3 cases in which no
      molecular alterations were detected. For the PDGFRalpha, we observed an in-frame
      deletion of codons 554 and 555 in a case which also showed a strong
      immunopositivity for the phosphorylated form of PDGFRalpha. PDGFRalpha expression
      was observed in 8 cases. We suggest that a more exhaustive mutational analysis of
      the c-KIT and PDGFRalpha genes should be performed to ascertain which cases would
      really benefit from a tyrosine kinase inhibitor therapy in SS.

PMID- 16106194
TI  - Recurrent sarcoidosis in lung transplant allografts: granulomas are of recipient
      origin.
AB  - INTRODUCTION: Sarcoidosis accounts for only 2.8% of lung transplants in the
      United States. It is, however, the most commonly reported disease to recur after
      lung transplantation. In most cases, recurrence is diagnosed as an incidental
      finding in transbronchial lung allograft biopsy (TBLAB) and is unrelated to
      clinical or radiologic abnormalities. The origin of the histiocytes composing the
      noncaseating granulomas in the allograft lung in patients with recurrent
      sarcoidosis (RS) was analyzed using DNA identity testing in 4 cases. MATERIAL AND
      METHODS: Native lung resections and corresponding transbronchial biopsies from
      patients who underwent lung transplantation for sarcoidosis between 1990 and 2004
      and who developed RS were gathered from the paraffin block archives of University
      of Pittsburgh Medical Center. Clinical parameters including age, sex, grade of
      rejection, number of episodes of RS, and follow-up were recorded. Native lungs
      and corresponding TBLAB showing granulomas consistent with RS were microdissected
      in cases where adequate material was available. DNA was extracted, and an ABI
      AmpflSTR commercial kit was used to simultaneously amplify 15 short tandem repeat
      (STR) loci as well as 1 marker for the XY chromosomes. The informative STR loci
      in native lung (pure recipient), nongranulomatous donor lung, and granulomas in
      donor lung were analyzed in 4 patients. The relative proportion of donor and
      recipient cells in the chimera was quantified using the fluorescence intensity of
      each peak on an electropherogram. FISH analysis using probes targeted to X and Y
      chromosomes was performed in a case of sex-mismatched lung transplantation.
      RESULTS: Eight patients with RS were identified. Two had bilateral lung
      transplantation, and the remaining 6 had single-lung transplantation. The age at
      transplantation ranged between 39 and 53. Five were females and 3 were men.
      Recurrent disease was diagnosed in 1 to 11 biopsies per patient and occurred
      first in the first 6 months following transplantation in 2 cases (25%), between 6
      months and 1 year in 2 other cases (25%), and between 1 and 2 years in 4 cases
      (50%). In 4 patients, sufficient material allowed for DNA analysis. Amplification
      failed in 1 of the 4 cases, while the other 3 were successful. Patient 1 showed
      no ACR and granulomatous inflammation of RS in TBLAB. Donor (D) to recipient (R)
      profile changed from "normal" donor lung (37% D, 63% R) to 15% D and 85% R DNA in
      the granuloma. In patient 2, the TBLAB showed minimal ACR and granulomatous
      inflammation. D to R profile changed from 75% D and 25% R in the "normal" D lung
      to 54% D and 46% R in the granuloma. Patient 3 showed no ACR and RS in TBLAB. D
      to R profile changed from 85% D and 15% R in the "normal" D lung to 71% D and 29%
      R in the granuloma. FISH analysis showed a predominance of male cells of
      recipient origin. CONCLUSIONS: DNA analysis of 3 cases of RS suggests that the
      presence of recurrent granulomas in the graft is associated with an increase in
      the percentage of recipient DNA in the epithelioid cell clusters, as confirmed by
      the FISH analysis of 1 case.

PMID- 16106195
TI  - Diagnosis of cat scratch disease with Bartonella henselae infection in formalin
      fixed paraffin-embedded tissues by two different PCR assays.
AB  - Cat scratch disease (CSD) is commonly caused by Bartonella henselae infection.
      Clinical history and histologic findings are often insufficient to establish a
      definitive diagnosis of CSD. We retrospectively studied formalin-fixed, paraffin
      embedded (FFPE) lymph nodes from 35 patients with histologically suspected CSD by
      2 different PCR assays and immunohistochemistry (IHC). The first primer pair
      amplified a 163-bp fragment of the 16S rRNA gene in 19 of the 35 cases (54%). The
      second primer pair amplified a 191-bp fragment of the henselae citrate synthase
      (gltA) gene in 17 of the 35 cases (49%). IHC identified the organisms in 8 of 33
      cases (24%). Fresh cultures of various Bartonella species showed a specific PCR
      product with an analytical sensitivity of 0.5 to 5 pg bacterial DNA. Bartonella
      species were identified by the unique size of the amplified PCR product. Twenty
      two lymph nodes without morphologic evidence or a history of CSD were negative by
      PCR and immunostaining. Tissues from a patient with Legionella pneumophila were
      also negative by PCR and immunostaining for CSD supporting the specificity of the
      PCR reaction. The specific PCR products of the B. henselae were confirmed by
      sequencing. Human beta-actin for each case was amplified to check the integrity
      of the DNA. Our data indicate that detection of Bartonella DNA by PCR is useful
      to confirm the diagnosis of CSD.

PMID- 16106196
TI  - Histologic, infectious, and molecular correlates of idiopathic spontaneous
      abortion and perinatal mortality.
AB  - The purpose of this study was to analyze the placental and neonatal tissues in
      fatal cases for a wide variety of infectious agents and cytokine expression.
      Placentas and corresponding neonatal tissues in 21 consecutive cases of
      idiopathic spontaneous abortion or perinatal death, before or within 2 days of
      birth, were tested for an infectious agent. The controls included 10 consecutive
      cases of fetal and placental tissues from therapeutic abortions, 5 placentas from
      unremarkable childbirths, and 11 placentas from cases of spontaneous abortion or
      perinatal death of known cause (ruptured uterus, placenta abruption, prolapsed
      cord). An intrauterine infection was noted in 16 of 21 (76%) of the placentas
      associated with neonatal mortality; in each case, the same infectious agent was
      found in the neonatal tissues, primarily the spleen. The most common infectious
      agent was enterovirus/coxsackie virus (10 cases); the histologic findings in the
      placenta were nonspecific. There was strong expression of TNF-alpha in the
      placenta and spleen of each of the cases of intrauterine infection and in none of
      the 26 controls. It is concluded that in utero infection and the associated
      cytokine up-regulation are responsible for many cases of unexplained fetal and
      neonatal loss.

PMID- 16106197
TI  - A novel frame shift mutation in the HMG box of the SRY gene in a patient with
      complete 46,XY pure gonadal dysgenesis.
AB  - Pure gonadal dysgenesis or Swyer syndrome is a sex-reversal disorder resulting
      from embryonic testicular regression sequences especially during the first few
      weeks of fetal life and is induced by mutations in the SRY gene. In the present
      report, we describe a nonmosaic XY sex-reversed female with pure gonadal
      dysgenesis. Molecular analysis using sequential PCR to detect Y chromosomal
      microdeletions showed the presence of SRY, ZFY and AZFa, b and c regions.
      Automated sequencing of the SRY region revealed a new mutation (deletion of A
      (adenine) in codon 82 at position +244), leading to a frame shift mutation within
      the helix I of the HMG-box domain. This mutation generates a truncated protein
      and is very likely to produce an impairment of SRY DNA binding activity. The
      present findings further support the functional importance of the putative DNA
      binding activity of the SRY HMG-box domain.

PMID- 16106198
TI  - Differential diagnosis between complete and partial mole by TSSC3 antibody
      completely correlates to DNA diagnosis.
AB  - Complete hydatidiform moles (CHMs) are a type of androgenetic fertilization
      without an ovum. Cases of CHM exhibit a generalized swelling of the villi and are
      known to be highly associated with persistent disease or carcinoma. In contrast,
      partial hydatidiform moles (PHMs) also show characteristic hydropic changes among
      the villi, but the incidence of secondary disease is relatively low. Because PHMs
      are fertilized by one ovum and two sperm and CHMs are fertilized by one or two
      sperm alone, we considered whether or not maternally imprinted genes might be
      useful for achieving a differential diagnosis. The validity of the imprinted
      genes in CHMs was assessed by implementation of a microarray technique. Among the
      genes examined, TSSC3, SLC22A1L, KCNQ1, and Decorin were shown to be down
      regulated, and TSSC3 was the most markedly suppressed of these genes. In this
      study, 20 cases of CHM, the diagnosis of which was confirmed by DNA polymorphism,
      were investigated. In all of these cases, the expression of TSSC3 was completely
      absent, as determined by Western blot analysis. Conversely, 12 cases of PHM, also
      diagnosed by DNA polymorphism, were examined here; in all of these 12 cases,
      TSSC3 was found to be expressed normally. Immunohistochemical (IHC) analysis also
      produced the same results. The complete silencing of TSSC3 in cases of CHM will
      provide a novel, convenient strategy for the diagnosis of molar lesions in the
      placenta.

PMID- 16106199
TI  - Application of a fluorescent PCR method for molecular diagnosis of posttransplant
      lymphoproliferative disorders on routine tissue sections.
AB  - Molecular detection of monoclonality can play an important role in the diagnosis
      of posttransplantation lymphoproliferative disorders (PTLD). To permit accurate
      molecular diagnosis of PTLD even on very small amounts of DNA extracted from
      routinely embedded histologic material, we adapted a commercially available PCR
      protocol (for FR-1, -2 and -3 regions), originally designed for use on
      fresh/frozen samples. We applied this approach on routine biopsy/surgical
      material of 10 PTLD (from nine patients). All three FR regions were always
      amplified, indicating that the extracted DNA was of medium quality. All five PTLD
      morphologically classified as lymphomas were monoclonal in at least one FR
      region. Thus, using the WHO histologic, immunohistochemical, and clinical
      criteria as the reference standard, the approach provided 100% sensitivity for
      detection of monoclonal malignancies, supporting the validity of the method. Of
      five specimens classified morphologically as polymorphic PTLD, three displayed a
      solitary IgH gene rearrangement peak, consistent with the presence of a
      monoclonal B-cell population (ie, monoclonal polymorphic PTLD). This rapid and
      straightforward procedure, which allows identification of a wide range of IgH
      rearrangements, could facilitate molecular analysis of PTLD in routine practice,
      while limiting consumption of valuable diagnostic material.

PMID- 16106200
TI  - Quantitative real-time PCR for quick simultaneous determination of therapy
      stratifying markers MYCN amplification, deletion 1p and 11q.
AB  - Amplification of the oncogene MYCN as well as deletions in 1p and 11q are
      important prognostic and in part therapy-stratifying factors in human
      neuroblastoma. Due to the increasing clinical relevance of these molecular
      markers, accurate and fast assessment of the status of MYCN, 1p, and 11q is
      essential. As 2 techniques are recommended to avoid artefacts and to circumvent
      technical limitations, we developed a real-time q-PCR assay using genomic DNA
      from frozen and paraffin-embedded tissue as template as an alternative to LOH
      analyses and Southern blot (SB) and in addition to fluorescence in situ
      hybridization (FISH). Determination of deletion or amplification was achieved by
      comparing the copy number of a target gene (TG from the region of interest) to an
      unaffected reference gene (RG) within the same chromosome. PCR raw data were
      normalized to a serial dilution standard curve and a ratio TG/RG was created. The
      ratio to define a deletion was set as 0.5 (= expected ratio 1 TG copy/2 RG
      copies), the amplification threshold was set as >10.0. Data were compared to
      results obtained by FISH and were consistent in 10 of 13 (77%) tumors with
      deletion 1p, 18 of 20 (90%) with deletion 11q, 12 of 12 (100%) with MYCN
      amplification, and 146 of 151 (97%) samples without any aberration. Three tumors
      with aberrations in 1p and 2 tumors with aberrations in 11q were detectable by
      FISH but not by PCR. Three cases indicated a deletion 11q, 1 tumor a deletion 1p
      by PCR only. Specificity was 98% for 1p and MYCN each and 92% for 11q.
      Sensitivity was 77% for 1p, 90% for 11q, and 100% for MYCN. The discrepant
      results were mostly caused by heterogeneous cell populations of the investigated
      tissue; the use of real-time q-PCR for the detection of chromosomal aberrances in
      NB enables a fast and reliable assessment of the 3 most relevant chromosomal
      aberrations simultaneously. As the assay does not require reference tissue, can
      be performed with small amounts of DNA, and allows the investigation of paraffin
      embedded material for the MYCN-status, it can be regarded alternative to LOH or
      SB analyses and in addition to FISH.

PMID- 16106201
TI  - DNA stabilization is critical for maximizing performance of fecal DNA-based
      colorectal cancer tests.
AB  - We have developed a multitarget, fecal DNA screening assay that detects the
      presence of gene-specific mutations and long DNA fragments associated with
      colorectal cancer (CRC). We continue to investigate methods that may be used to
      optimize clinical sensitivity. The goals of this investigation are to establish
      how sample handling conditions affect the stability of DNA in stool, thereby
      potentially limiting clinical sensitivity, and to determine conditions to
      ameliorate DNA degradation. A study was run comparing paired sample aliquots.
      Quantitative PCR data for matched aliquots was used to determine first the effect
      of sample incubation on total recovery and integrity of DNA, then the effect of
      stabilization buffer addition to stool on recoverable DNA, and finally the impact
      of buffer addition on assay sensitivity. Comparison of quantitative PCR data for
      paired aliquots shows that the amount of recoverable human DNA is negatively
      affected by storing stool samples (N = 43) at room temperature for > or =36 hours
      (P = 0.0018). However, the addition of stabilization buffer leads to a
      significant increase in recovery of DNA (P = 0.010), compared with samples
      incubated without buffer. Whereas the DNA Integrity Assay (DIA) is found to be
      sensitive to DNA degradation (sensitivity was reduced by 82%; P = 0.0002), point
      mutation marker sensitivity is more refractory. Overall, DNA can be stabilized by
      addition of buffer to the sample, leading to increased assay sensitivity.

PMID- 16106207
TI  - Presidential address.

PMID- 16106208
TI  - The use and misuse of electronic patient data.
AB  - This article highlights patient privacy rights, briefly discusses a few of the
      many federal, state, and local regulatory laws protecting patient confidentiality
      and privacy electronically, and briefly reviews several case decisions in this
      area. Implications for infusion nurses also are presented.

PMID- 16106209
TI  - Proteasome inhibition in cancer therapy.
AB  - Multiple myeloma is an incurable malignancy diagnosed for approximately 15,000
      individuals in the United States each year. The advances in high-dose
      chemotherapy and transplantation have improved the overall survival rates and
      allowed individuals to remain off therapy for longer periods, but relapses are
      inevitable. The novel proteasome inhibitor, bortezomib, is the first in its class
      to be approved for patients with relapsed multiple myeloma. This article
      discusses the proteasome pathway and its role in the regulation of cell growth
      and survival. During clinical trials, most side effects were manageable with
      appropriate interventions. The common toxicities are outlined in this article,
      along with symptom management guidelines for the infusion nurse. The role of the
      infusion-oncology nurse is vital to ensuring the safe and appropriate
      administration of bortezomib, and the nurse plays a key role in the ongoing care
      of these patients.

PMID- 16106210
TI  - Developing practice guidelines for the administration of intravenous
      immunoglobulin.
AB  - As the use of intravenous immunoglobulin (IGIV) continues to expand, infusion
      nurses have a greater need for a comprehensive understanding of the product,
      patient risk factors, and comorbidities when developing guidelines for
      administering IGIV. Because immunoglobulin therapy is a blood derivative product,
      many nurses may not have as much experience administering this type of infusion.
      This article provides an in-depth overview of immunoglobulin therapy and helps to
      define the infusion nurse's major role in coordinating, assessing, and ensuring
      patient safety during IGIV administration.

PMID- 16106211
TI  - Universal leukocyte reduction: Is it appropriate medical practice or not?
AB  - This article discusses the evidence for the generally accepted uses of leukocyte
      reduced blood and the controversy over leukocyte reduction and transfusion
      related immunomodulation. A perspective is provided on the continued need for
      leukocyte reduction on the part of all patients in the United States.

PMID- 16106213
TI  - The pathobiology of amyotrophic lateral sclerosis: a proteinopathy?
AB  - Amyotrophic lateral sclerosis (ALS) is increasingly considered to be a disorder
      of multiple etiologies that have in common progressive degeneration of both upper
      and lower motor neurons, ultimately giving rise to a relentless loss of muscle
      function. This progressive degeneration is associated with heightened levels of
      oxidative injury, excitotoxicity, and mitochondrial dysfunction--all occurring
      concurrently. In this article, we review the evidence that suggests, in common
      with other age-dependent neurodegenerative disorders, that ALS can be considered
      a disorder of protein aggregation. Morphologically, this is evident as Bunina
      bodies, ubiquitin-immunoreactive fibrils or aggregates, neurofilamentous
      aggregates, mutant copper/zinc superoxide dismutase (SOD1) aggregates in familial
      ALS variants harboring mutations in SOD1, peripherin-immunoreactive aggregates
      within spinal motor neurons and as neuroaxonal spheroids, and in an increasingly
      greater population of patients with ALS with cognitive impairment, both intra-
      and extraneuronal tau aggregates. We review the evidence that somatotopically
      specific patterns of altered kinase and phosphatase activity are associated with
      alterations in the phosphorylation state of these proteins, altering either
      solubility or assembly characteristics. The role of nonneuronal cells in
      mediating motor neuronal injury is discussed in the context of alterations in
      tyrosine kinase activity and enhanced protein phosphorylation.

PMID- 16106214
TI  - Visualization of newly deposited tau in neurofibrillary tangles and neuropil
      threads.
AB  - Neurofibrillary tangles (NFTs) and neuropil threads (NTs), the major hallmark of
      Alzheimer disease (AD), are composed of the microtubule-associated protein tau
      that has undergone posttranslational modifications, including deamidation and
      isomerization on asparaginyl or aspartyl residues. Because such modifications
      represent protein aging, we generated 2 antibodies, TM4, specific for Asp-387 of
      tau, and iD387, specific for isoAsp-387 of tau, to investigate the evolution of
      NFTs and NTs. On Western blots of Sarkosyl-insoluble fractions, TM4 strongly
      labeled paired helical filament-tau (PHF-tau), whereas iD387 preferentially
      labeled PHF smear. Thus, it is reasonable to postulate that TM4-labeled tau
      (unmodified tau species) represents more recent deposition, and iD387-labeled tau
      (modified tau species) represents earlier deposition. Unexpectedly, TM4
      immunostained even highly evolved NFTs, suggesting that deposition of newly
      produced tau continues until neuronal death. iD387 labeled the whole profile of
      NFTs up to distal dendritic branches, whereas TM4 staining was localized to
      particular portions of NFTs in proximal dendrites and neuronal perikarya. In NTs,
      TM4 preferentially labeled the outer portion, whereas iD387 intensely labeled the
      core portion. Based on TM4-positive NFT counts and total NFT counts, we speculate
      that NFTs in the human hippocampus are produced at a constant rate irrespective
      of the disease stage.

PMID- 16106215
TI  - Ectopic expression of Musashi-1 in Alzheimer disease and Pick disease.
AB  - Abnormal accumulation of proteins in filamentous cytoplasmic inclusions is a
      hallmark of several neurodegenerative disorders, including Alzheimer disease (AD)
      and Pick disease (PD). Musashi-1 (Msi-1), an RNA-binding protein associated with
      neural progenitor cells, has been shown by others to increase the accumulation of
      tau isoforms in intracellular inclusions in frontotemporal dementia and
      parkinsonism linked to chromosome 17. We investigated the expression of Msi-1 in
      the hippocampus of AD, PD, and aged normal control subjects using
      immunohistochemistry. Comparison of immediately adjacent serial sections stained
      using the modified Bielschowsky method and immunostained for Msi-1 showed that
      Msi-1 was present in 83 +/- 6% of neurofibrillary tangle bearing neurons in AD
      and 94 +/- 14% of Pick bodies in PD specimens. Aged control hippocampus
      demonstrated virtually no Msi-1 immunostaining. The presence of Msi-1 in a
      significant percentage of neurons containing cytoplasmic inclusions in 2
      different neurodegenerative diseases suggests that it may play a role in the
      pathogenesis of these lesions.

PMID- 16106216
TI  - Transplantation of human umbilical cord blood-derived adherent progenitors into
      the developing rodent brain.
AB  - The results of several recent studies suggest that human umbilical cord blood
      (HUCB)-derived cells have the potential to undergo neural differentiation both in
      vitro and in vivo. Transplantation into the embryonic ventricular zone provides a
      unique opportunity to study the migration and differentiation of nonneural
      somatic progenitor cells in response to instructive cues within the developing
      neuroepithelium. We isolated an adherently growing population of HUCB-derived
      cells expressing CD13, CD29, CD49e, CD71, CD73, CD166, Flk-1, and vimentin but
      lacking CD34 and CD45. On transplantation into the ventricles of embryonic day
      16.5 rat embryos, these cells formed subventricular clusters that extended into a
      variety of host brain regions, including striatum, cortex, hippocampus, thalamus,
      hypothalamus, tectum, pons, and cerebellum. Donor cells identified with an
      antibody to human nuclei or human-specific DNA in situ hybridization maintained
      expression of their original marker antigens and showed no expression of the
      neural markers MAP2 and NeuN (neurons), GFAP (astrocytes), and CNP
      (oligodendrocytes). In contrast to grafted primary neural cells, they remained
      largely confined to subventricular clusters with little evidence for
      intraparenchymal integration. Thus, the neurogenic environment of the embryonic
      ventricular zone does not promote the elaboration of a neural phenotype in HUCB
      derived cells.

PMID- 16106217
TI  - Subtle autonomic and respiratory dysfunction in sudden infant death syndrome
      associated with serotonergic brainstem abnormalities: a case report.
AB  - Sudden infant death syndrome (SIDS) is characterized by a sleep-related death in
      a seemingly healthy infant. Previously, we reported abnormalities in the
      serotonergic (5-HT) system of the medulla in SIDS cases in 2 independent
      datasets, including in the Northern Plains American Indians. The medullary 5-HT
      system is composed of 5-HT neurons in the raphe, extra-raphe, and arcuate nucleus
      at the ventral surface. This system is thought to modulate respiratory and
      autonomic function, and thus abnormalities within it could potentially lead to
      imbalances in sympathetic and parasympathetic tone. We report the case of a full
      term American Indian boy who died of SIDS at 2 postnatal weeks, and who had
      subtle respiratory and autonomic dysfunction measured prospectively on the second
      postnatal day. Cardiorespiratory assessment of heart rate variability suggested
      that the ratio of parasympathetic to sympathetic tone was higher than normal in
      active sleep and lower than normal in quiet sleep in this case. At autopsy,
      arcuate nucleus hypoplasia and 5-HT receptor-binding abnormalities in the arcuate
      nucleus and other components of the medullary 5-HT system were found. This case
      suggests that medullary 5-HT system abnormalities may be able to be identified by
      such physiological tests before death. Replication of these findings in a large
      population may lead to the development of predictive cardiorespiratory assessment
      tools for future screening to identify infants with medullary 5-HT abnormalities
      and SIDS risk.

PMID- 16106218
TI  - Sphingosine kinase-1 expression correlates with poor survival of patients with
      glioblastoma multiforme: roles of sphingosine kinase isoforms in growth of
      glioblastoma cell lines.
AB  - Sphingosine-1-phosphate is a bioactive lipid that is mitogenic for human glioma
      cell lines by signaling through its G protein-coupled receptors. We investigated
      the role of sphingosine-1-phosphate receptors and the enzymes that form
      sphingosine-1-phosphate, sphingosine kinase (SphK)-1, and -2 in human
      astrocytomas. Astrocytomas of various histologic grades expressed three types of
      sphingosine-1-phosphate receptors, S1P1, S1P2, and S1P3; however, no significant
      correlation with histologic grade or patient survival was detected. Expression of
      SphK1, but not SphK2, in human astrocytoma grade 4 (glioblastoma multiforme)
      tissue correlated with short patient survival. Patients whose tumors had low
      SphK1 expression survived a median 357 days, whereas those with high levels of
      SphK1 survived a median 102 days. Decreasing SphK1 expression using RNA
      interference or pharmacologic inhibition of SphK significantly decreased the rate
      of proliferation of U-1242 MG and U-87 MG glioblastoma cell lines. Surprisingly,
      RNA interference to knockdown SphK2 expression inhibited glioblastoma cell
      proliferation more potently than did SphK1 knockdown. SphK knockdown also
      prevented cells from exiting G1 phase of the cell cycle and marginally increased
      apoptosis. Thus, SphK isoforms may be major contributors to growth of
      glioblastoma cells in vitro and to aggressive behavior of glioblastoma
      multiforme.

PMID- 16106219
TI  - Astrocytes produce dendritic cell-attracting chemokines in vitro and in multiple
      sclerosis lesions.
AB  - As a result of their close association with the blood-brain barrier, astrocytes
      play an important role in regulating the homing of different leukocyte subsets to
      the inflamed central nervous system (CNS). In this study, we investigated whether
      human astrocytes produce chemokines that promote the migration of myeloid
      dendritic cells (DCs). By reverse transcriptase-polymerase chain reaction and
      enzyme-linked immunosorbent assay, we show that cultured human astrocytes
      stimulated with interleukin-1beta and tumor necrosis factor produce CCL2, CCL3,
      CCL4, CCL5, CCL20, and CXCL12 that act on immature DCs, but not CCL19 and CCL21,
      2 chemokines specific for mature DCs. Compared with controls, supernatants of
      cytokine-stimulated astrocytes are more effective in promoting the migration of
      immature monocyte-derived DCs (iMDDCs). Desensitization of CXCR4 (receptor for
      CXCL12), CCR1-3-5 (shared receptors for CCL3-4-5), and CCR6 (receptor for CCL20)
      on iMDDC reduces cell migration toward astrocyte supernatants, indicating that
      astrocytes release biologically relevant amounts of iMDDC-attracting chemokines.
      By immunohistochemistry, we show that CXCL12 and, to a lesser extent, CCL20 are
      expressed by reactive astrocytes in multiple sclerosis lesions. These data lend
      support to the idea that astrocyte-derived chemokines may contribute to immature
      DC recruitment to the inflamed CNS.

PMID- 16106220
TI  - Accumulation of prion protein in the peripheral nervous system in human prion
      diseases.
AB  - After the finding that anti-prion antibodies stain sensory and sympathetic
      ganglia in variant Creutzfeldt-Jakob disease (vCJD), it was suggested that this
      localization supported the oral route of entry. However, prion accumulation
      subsequently also appeared in the peripheral nervous system (PNS) in sporadic
      cases. This study aims at evaluating the extent of prion protein accumulation in
      the PNS in all clinicopathologic subgroups of the disorder, with the exception of
      the familial and sporadic forms of fatal insomnia. Patients included 2 vCJD
      cases, 2 Gerstmann-Straussler-Scheinker (GSS), 2 iatrogenic (iCJD), and 16
      sporadic CJD (sCJD) cases. Gasserian (17) and spinal (9), celiac (2) and thoracic
      sympathetic (one) ganglia, spinal cord and medulla of one vCJD, 2 GSS, one iCJD,
      and 5 sCJD cases were examined. Immunostained sensory ganglia were seen in both
      vCJD, both iCJD, one GSS, and 10 sCJD cases; the celiac ganglion was positive in
      one of two sCJD cases, and the spinal dorsal horn and the medullary sensory
      nuclei were positive in one patient with vCJD, one with iCJD, and 3 with sCJD.
      Western blot demonstrated presence of PrP in the gasserian ganglion of one
      patient with sCJD. Accumulation of prion in ganglia (including autonomic) of the
      PNS, shared by all subgroups of spongiform encephalopathy, and in the dorsal
      horns and medullary sensory nuclei, shows that the sensory route is involved in
      the trafficking of this protein.

PMID- 16106221
TI  - Basement membrane proteins in multiple sclerosis-associated inflammatory cuffs:
      potential role in influx and transport of leukocytes.
AB  - Perivascular accumulation of macrophages and lymphocytes is a prominent feature
      of multiple sclerosis (MS) pathology. To enter the brain parenchyma, immune cells
      need to migrate across the blood-brain barrier through a number of well-defined
      processes. So far, little attention has been given to the role of the basement
      membrane (BM) in leukocyte recruitment into the central nervous system (CNS).
      Here, we characterized the molecular composition of the vascular and astroglial
      BMs in chronic active and active MS lesions with large perivascular infiltrates
      using antibodies directed against several extracellular matrix (ECM) proteins. A
      differential expression of specific laminin chains in vascular and astroglial BMs
      was observed. Interestingly, we found fiber-like depositions of ECM within
      inflammatory cuffs. These structures were immunopositive for several laminin
      isoforms, fibronectin, collagen IV, and heparan sulfate proteoglycans.
      Strikingly, we observed myelin-laden macrophages in the Virchow-Robin space.
      Because BM molecules are in close contact with these cells, we postulate that BM
      proteins within inflammatory cuffs may serve as a conduit network and therefore
      facilitate the transport of myelin-containing phagocytes out of the CNS toward
      peripheral lymph nodes.

PMID- 16106222
TI  - Ubiquitin immunohistochemistry suggests classic motor neuron disease, motor
      neuron disease with dementia, and frontotemporal dementia of the motor neuron
      disease type represent a clinicopathologic spectrum.
AB  - One of the characteristic pathologic changes in classic motor neuron disease
      (MND) is the presence of ubiquitin-immunoreactive (ub-ir) inclusions in the
      cytoplasm of lower motor neurons. In addition, cases of MND with dementia (MND-d)
      also have ub-ir neuronal cytoplasmic inclusions and dystrophic neurites in
      extramotor neocortex and hippocampus. Although this extramotor pathology is a
      highly sensitive marker for dementia in MND, similar changes are found in a
      subset of patients with frontotemporal dementia (FTD) with no motor symptoms (FTD
      MND type). The purpose of this study is to more fully describe and compare the
      pattern of ub-ir pathology in these 3 conditions. We performed ubiquitin
      immunohistochemistry on postmortem tissue, representing a wide range of
      neuroanatomic structures, in cases of classic MND (n = 20), MND-d (n = 15), and
      FTD-MND type (n = 15). We found the variety of morphologies and the anatomic
      distribution of ub-ir pathology to be greater than previously documented.
      Moreover, the degree of overlap suggests that MND, MND-d, and FTD-MND type
      represent a spectrum of clinical disease with a common pathologic substrate. The
      only finding restricted to a specific subgroup of patients was the presence of ub
      ir neuronal intranuclear inclusions in some cases of familial FTD.

PMID- 16106223
TI  - Complement as a biomarker in multiple sclerosis.

PMID- 16106225
TI  - Epidural anesthesia: a resource to use judiciously.

PMID- 16106226
TI  - Single-room design in the NICU: making it work for you.

PMID- 16106227
TI  - Couplet care after cesarean delivery: creating a safe environment for mother and
      baby.

PMID- 16106228
TI  - Educational resources from the March of Dimes resources for nurses and families.

PMID- 16106229
TI  - Cholestasis of pregnancy: a review of the evidence.
AB  - Intrahepatic cholestasis of pregnancy is a rare disorder, predominately occurring
      during the third trimester of pregnancy and characterized by pruritus, jaundice,
      and biochemical disturbances in liver enzymes. While intrahepatic cholestasis of
      pregnancy poses little maternal risk, there is significant risk to the fetus such
      as preterm delivery, non-reassuring fetal status, meconium staining, and
      perinatal mortality. Current evidence proposes susceptibility to derangements in
      the sulfation of steroid compounds, affecting the metabolism of progesterone and
      bile acids in the fetal/placental compartment. Treatment with ursodeoxycholic
      acid is suggested, coupled with close maternal-fetal surveillance and delivery as
      close to term as possible.

PMID- 16106230
TI  - Terrorism and the pregnant woman.
AB  - Pregnant women and their infants are vulnerable, during and following a terrorist
      event. The threat poses a dual challenge: assessment and treatment of the trauma
      patient, and assessment and treatment of the pregnant woman. Some injuries in the
      pregnant woman are obvious; some injuries may not be easily observable. Obtaining
      an obstetric history coupled with careful nursing assessments ensure prompt and
      appropriate emergency treatment. Obstetricians, certified nurse midwives, nurse
      practitioners, and perinatal nurses are uniquely qualified to perform these
      assessments because of their understanding of the changes in maternal physiology
      and anatomy during pregnancy. The pregnant woman can sustain injuries owing to
      trauma or exposure to biological, chemical, or radiological agents. Following
      trauma, assessment of the gravid uterus is needed, as well as the use of
      traditional diagnostic, pharmacologic, or resuscitative procedures. The perinatal
      care provider must be familiar with the hematological changes that normally
      suppress any immune response to the fetus and how these protective changes
      increase the risk from biological agents, such as anthrax and smallpox.

PMID- 16106232
TI  - Attitudes of nurses toward perinatal bereavement: findings from a study in Hong
      Kong.
AB  - AIM: Nurses' attitudes toward perinatal bereavement care are explored by
      identifying profiles of nurses working in 2 obstetrics and gynecology units in
      Hong Kong. Relationships between nurses' attitudes toward bereavement supports,
      need for bereavement education, and hospital policy are explored. RESEARCH
      METHOD: A descriptive, correlational survey design was used, and 169 nurses
      recruited from an obstetric and gynecology (ob-gyn) unit at 2 local public
      hospitals in Hong Kong completed a structured questionnaire. OUTCOME MEASURES:
      Attitudes toward perinatal bereavement support; required support and education
      needs for nurses on bereavement care. FINDINGS: Two-step cluster analysis yielded
      2 clusters. Cluster 1 consisted of 55.6% (n = 94) and cluster 2 consisted of
      44.3% (n = 75) of nurses. Cluster 2 nurses were younger and had less ob-gyn
      experience, more junior ranking, and less education than cluster 1 nurses.
      Cluster 1 nurses had additional midwifery and bereavement care education,
      personal grieving experiences, and experience handling grieving clients. The
      majority held positive bereavement care attitudes, but only 29.6% (n = 50) had
      bereavement-related education. Attitudes toward bereavement care were positively
      correlated with educational needs (r(s) = 0.52) and hospital policy support (r(s)
      = 0.56). CONCLUSIONS: Hong Kong nurses emphasized the need for increased
      bereavement care knowledge and experience, improved communication skills, and
      greater hospital and team members' support. Findings may be used to improve
      support of nurses, to ensure sensitive bereavement care in perinatal settings,
      and to enhance nursing curricula. The desire of Hong Kong nurses for bereavement
      education highlights the universality of grief for a lost infant, regardless of
      cultural differences in approaching emotional topics. This study may help nurses
      in the United States and elsewhere gain a broader perspective in this area.

PMID- 16106233
TI  - The legal landscape at the threshold of viability for extremely premature
      infants: a nursing perspective, part II.
AB  - This is the second of a 2-part article exploring the legal landscape overlying
      the difficult decisions that can confront a family with an extremely premature
      infant at the threshold of viability. In Part I, recent legal regulations and
      litigation were analyzed to show that the baby doe regulations are largely inert
      and that recent litigation arises out of state laws and regulations. Part II
      takes up the analysis to show that the common thread through all these conflicts,
      and the subsequent litigation, is a failure to obtain parental consent for the
      course of treatment at issue. The author argues that the central focus of all
      parties seeking to minimize legal risks in these situations must be on creating a
      transparent decision-making process that includes the parents from the onset.
      Nurses play a pivotal role in that process and are supported broadly by the
      professional guidelines of the American Nurses Association, the Association of
      Women's Health Obstetric and Neonatal Nurses, the National Association of
      Neonatal Nurses, the American Academy of Pediatrics, and the Principles of Family
      Centered Neonatal Care.

PMID- 16106235
TI  - Nutritive sucking research: from clinical questions to research answers.
AB  - Nutritive sucking and feeding behaviors have the potential to predict
      developmental outcomes. Research is beginning to connect nutritive sucking
      behaviors and neurodevelopmental outcomes, providing an important understanding
      of how infants develop during the first year of life. A program of research has
      evolved using sucking behaviors as the primary indices of both maturation and
      development in preterm infants. Clinical questions were the guiding force behind
      5 funded grants from the National Institutes of Health and many small grants from
      foundations and professional organizations. Three of the National Institutes of
      Health studies were research based and 2 were for development of the feeding
      instrumentation. These cumulative grants have generated a significant volume of
      data; highlights and clinical implications of this work are presented in this
      article.

PMID- 16106236
TI  - Milk volume on day 4 and income predictive of lactation adequacy at 6 weeks of
      mothers of nonnursing preterm infants.
AB  - Lactating mothers of preterm infants who are pump-dependent are at high risk for
      difficulty maintaining an adequate milk supply. This article reports the
      naturally occurring volume of milk removed from the breast by mechanical
      expression over time for 81 mothers of nonnursing preterm infants from 4 tertiary
      care centers in the Midwest. Baseline variables (infant gestation in weeks;
      intended length in weeks to breastfeed; number of hours post-delivery to first
      breast stimulation; infant weight in grams; timing of decision to provide
      mother's milk; income; maternal education, kangaroo care during week 1; previous
      breastfeeding experience; white, non-Hispanic) and day 4 variables (milk volume,
      frequency of pumping) were explored for predicting milk adequacy at week 6. Using
      the significant predictive variables of milk levels at day 4 and income, the
      logistic regression accurately classified 85% of the 40 mothers with inadequate
      milk production (<500 mL/d) and 85.5% of the 41 mothers with adequate milk
      production (> or = 500 mL/d). While controlling for income, the 27 mothers with
      lowest milk production at 4 days were 9.5 times more likely to have an inadequate
      milk supply at 6 weeks than the 54 mothers with higher milk production. While
      controlling for day 4 milk production, lower annual income mothers (< dollar
      50,000) were 5 times more at risk of inadequate milk production than those with
      high income (> or = dollar 50,000) at week 6. This study emphasizes the
      importance of the amount of milk volume expressed in the early postpartum period
      during lactogenesis. In addition, neonatal nurses need to be cognizant that
      income levels may make a difference in milk production.

PMID- 16106237
TI  - [CD4+CD25+ T regulatory cells: their physiology and role in modulating immune
      response].
AB  - Understanding the role of immune system homeostatic balance is crucial for a
      better understanding of the pathogenesis of many diseases. The efficient
      regulation of immune response has been recently investigated in numerous studies
      that emphasize the important role of CD4+CD25+ regulatory T cells. These
      regulatory cells suppress the proliferation and cytokine secretion of effector
      cells directly via cell-cell contact and probably indirectly via TGF-beta. This
      makes T regulatory cells responsible for the control and suppression of
      inappropriate immune response to self antigens. Moreover, CD4+CD25+ regulatory T
      cells have an important function in the immunopathology of cancer,
      allotransplantion, and allergy. Based on murine and human studies, this review
      presents a characterization of the origin, phenotype, and function of CD4+CD25+
      regulatory T cells. In addition, we show a hypothetical mode of the in vivo
      action of regulatory T cells, which play a central role in maintaining immune
      homeostasis.

PMID- 16106238
TI  - [CD4+CD25+ T regulatory cells in pathophysiology and therapy of immunologic
      diseases].
AB  - Naturally arising CD4+CD25+ T regulatory cells actively maintain immunological
      tolerance to self and non-self antigens. Treg cells inhibit proliferative
      response and cytokine production by effector cells, basically via cell-cell
      contact. Deficiency or dysfunction in these cells may result in autoimmune
      diseases. Treg cells may also influence the outcome of infection, cancer,
      transplantation, allergy, and even some forms of infertility. Enhancement or
      blockade of natural Treg cells may represent a therapeutic approach to many
      immunopathologies. However, Treg cells act like a 'double-edged sword', which is
      why all therapeutic manipulation of these cells on humans should be done with
      great caution.

PMID- 16106239
TI  - [Kidney transplantation in highly sensitized patients].
AB  - The broad alloreactivity of antibodies in patients awaiting renal graft is a
      barrier to access to transplantation and may be the cause of acute or chronic
      graft dysfunction. Proper management of highly sensitized patients allows safe
      graft transplant and reduced wait-ing time. First, serum profiles from the
      patients should be distributed to all transplant centers for typing to every well
      HLA-matched donor. Secondly, a precise profiling of antibodies must be made,
      including differentiation of autoantibodies and alloantibodies, and determining
      the levels and specificities of alloantibodies. Thirdly, only well-matched
      kidneys are to be transplanted, particularly important with regard to HLA-DR and
      HLA-B antigens. The identification of acceptable mismatches in HLA class I and
      class II antigens and defining the probability of a negative cross-match can help
      finding a donor. Fourthly, pretransplant cross-matching should be performed by a
      complement-dependent cytotoxicity method (CDC) with T and B lymphocytes and
      antihuman globulin augmentation (AHG-CDC), flow cytometry (FC), or
      immunoenzymatic assay (ELISA) with current and historical sera. The desensitizing
      protocols should be kept in reserve for highly sensitized patients who are
      unlikely to receive a graft. Two of these protocols are
      plasmapheresis/immunoadsorption with low doses of intravenous immune globulin
      anti-CMV (100 mg/kg b.w.) or high doses of immune globulin (2 g/kg b.w.).
      Immunosuppressive treatment should consist of decisive induction and maintenance
      of immunosuppression, e.g. with ATG, tacrolimus, and mycophenolate mofetil. The
      monitoring of anti-donor antibodies after transplantation is obligatory. The
      symptoms of antibody-mediated rejection are graft dysfunction, and characteristic
      pathologies including C4d staining, vasculitis, neutrophil infiltration, and
      circulating donor-specific antibody.

PMID- 16106240
TI  - [Tau-pathies: neurodegenerative diseases with pathology involving tau protein].
AB  - Microtubule-associated protein tau (MAP-tau) plays an important role in
      stabilizing neuronal structure, in axonal transport, regulating cellular
      division, and apoptotic processes. In recent years the structure and functions of
      MAP-tau, as well as its physiological changes and pathology, have been
      extensively studied. Degenerative diseases of the central nervous system having
      MAP-tau involved in their pathogenesis are called tau-pathies. This group
      includes Alzheimer's disease, frontotemporal dementia, progressive supranuclear
      palsy, and corticobasal degeneration. The authors present the clinical pictures
      of these diseases (with the dominant features of dementia), and current
      possibilities in their diagnosis and treatment. MAP-tau as a marker for
      neurodegenerative process is already used in the diagnosis of tau-pathies.
      Further studies on its pathology may also give rise to some new therapeutic
      strategies.

PMID- 16106241
TI  - Protein homocysteinylation: a new mechanism of atherogenesis?
AB  - An increased concentration of homocysteine is an important risk factor of
      atherosclerosis; however, the mechanism of the proatherogenic effect of this
      amino acid is not yet known. Studies performed during the last two decades
      suggest that the atherogenic effect of homocysteine may be accounted for by
      homocysteine thiolactone (HCTL). Homocysteine is nonspecifically activated by
      methionyl-tRNA synthetase; however, it is not transferred to tRNA and
      incorporated into proteins, but is transformed to a cyclic thioester,
      homocysteine thiolactone. HCTL is highly reactive and acylates free amino groups
      of protein lysine residues, the process referred to as protein N
      homocysteinylation. Various plasma proteins are homocysteinylated in vitro and in
      vivo. Homocysteinylation results in the incorporation of additional thiol groups
      which may alter the physicochemical properties and biological activity of
      proteins. In particular, homocysteinylation of low-density lipoproteins (LDLs)
      increases their susceptibility to oxidation and accelerates their uptake by
      macrophages. In addition, homocysteinylated LDL elicit humoral immune response.
      Anti-homocysteinyllysine antibodies are detected in plasma of healthy humans and
      their titer is elevated in patients with ischemic heart disease or ischemic
      cerebral stroke. Homocysteine thiolactone is hydrolyzed to homocysteine by
      paraoxonase (PON), a calcium-dependent esterase synthesized in the liver and
      contained in plasma high-density lipoproteins (HDLs). Protein homocysteinylation
      may contribute to accelerated atherogenesis in individuals with
      hyperhomocysteinemia.

PMID- 16106242
TI  - [Dopamine: not just a neurotransmitter].
AB  - Dopamine is an important endogenous catecholamine which exerts widespread effects
      both in neuronal (as a neurotransmitter) and non-neuronal tissues (as an
      autocrine or paracrine agent). Within the central nervous system, dopamine binds
      to specific membrane receptors presented by neurons and it plays the key role in
      the control of locomotion, learning, working memory, cognition, and emotion. The
      brain dopamine system is involved in various neurological and psychiatric
      disturbances such as Parkinson's Disease, schizophrenia, and amphetamine and
      cocaine addiction. Thus, this system is the major target of powerful drugs
      applied in the treatment of neuropsychiatric diseases. Physiological functions of
      the brain dopamine system are well recognized. However, dopamine biosynthesis
      does not only occur in neurons, but also in peripheral tissues. Dopamine
      receptors have been described in the kidney, pancreas, lungs, and in numerous
      blood vessels outside the central nervous system. Renal dopamine is now
      recognized as an important regulator of sodium extraction and electrolyte
      balance, while defective renal dopamine production and/or dopamine receptor
      function may contribute to the development of various forms of human and animal
      hypertension. This article gives a brief overview of the importance of dopamine
      acting as a neurotransmitter and peripheral hormone. Special consideration is
      given to: (i) biochemical disturbances occurring in both brain and kidneys in
      various diseases and (ii) current therapy correcting disturbances in dopamine
      systems.

PMID- 16106243
TI  - [The role of lactoferrin in the proper development of newborns].
AB  - Colostrum and milk contain, in addition to nutritional constituents, also
      proteins crucial for the normal development of the offspring. Lactoferrin (LF)
      belongs to the family of iron-binding proteins and exhibits a wide spectrum of
      antimicrobial and immunotropic properties. LF is particularly resistant to
      proteolytic degradation in alimentary tract, in contrast to other milk proteins,
      e.g. casein. In any case, LF-derived peptides also possess potent antibacterial
      activities. LF is absorbed from the intestine by means of specific receptors
      located on brush border cells. Administered orally, LF stimulates both local and
      systemic immune response. LF plays a role in the absorption of nutrients. The
      protein can deliver such metal ions as iron, manganese, and zinc and facilitate
      the absorption of sugars. LF stimulates the proliferation of gut endothelial
      cells and the growth of gut-associated lymphatic follicles. This property
      suggests the possibility of applying LF in premature infants and patients with
      damaged intestinal mucus. LF controls the proper composition of the gut
      microflora. It suppresses the growth of pathogenic bacteria while promoting the
      multiplication of nonpathogenic Lactobacillus and Bifidobacterium. Newborns fed
      an artificial diet develop harmful microflora (Enterococcus, Enterobacter,
      Bacteroides, Escherichia). The non-pathogenic microflora ensures low pH, produces
      some vitamins, increases the activity of NK cells, T lymphocytes, and
      macrophages, promotes the production of protective immunoglobulins, and lowers
      the risk of allergies. In studies on mice, LF was found to be protective in
      bacteremia and endotoxemia. The protein stimulates the activity of reticulo
      endothelial system cells and elicits myelopoiesis, thus increasing the killing
      and clearance of bacteria. In the model of experimental endotoxemia, LF inhibits
      the activity of pro-inflammatory cytokines, nitric oxide, and reactive forms of
      oxygen. LF can also promote the differentiation of T and B cells from their
      immature precursors and increases the activity of NK and LAK cells. It also
      protects against the toxicity of reactive oxygen radicals. This property may be
      particularly relevant when baby food, based on modified cow's milk, contains
      mineral iron, which may be a source of harmful free radicals. In summary, it is
      obvious that natural human milk has the best value for newborns. Supplementation
      of artificial baby food with LF seems essential to improve the protective and
      immunoenhancing property of this kind of diet. It is clear that cow's milk is not
      appropriate for human newborns. Cow's milk contains 50 times less LF, only traces
      of lysozyme, and lower concentrations of other whey proteins and immunologically
      relevant immunoglobulins. Therefore commercially available baby foods (United
      States, Japan) are supplemented with LF.

PMID- 16106244
TI  - REporting recommendations for tumour MARKer prognostic studies (REMARK).

PMID- 16106245
TI  - REporting recommendations for tumour MARKer prognostic studies (REMARK).
AB  - Despite years of research and hundreds of reports on tumour markers in oncology,
      the number of markers that have emerged as clinically useful is pitifully small.
      Often initially reported studies of a marker show great promise, but subsequent
      studies on the same or related markers yield inconsistent conclusions or stand in
      direct contradiction to the promising results. It is imperative that we attempt
      to understand the reasons that multiple studies of the same marker lead to
      differing conclusions. A variety of methodological problems have been cited to
      explain these discrepancies. Unfortunately, many tumour marker studies have not
      been reported in a rigorous fashion, and published articles often lack sufficient
      information to allow adequate assessment of the quality of the study or the
      generalisability of the study results. The development of guidelines for the
      reporting of tumour marker studies was a major recommendation of the US National
      Cancer Institute and the European Organisation for Research and Treatment of
      Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000.
      Similar to the successful CONSORT initiative for randomised trials and the STARD
      statement for diagnostic studies, we suggest guidelines to provide relevant
      information about the study design, preplanned hypotheses, patient and specimen
      characteristics, assay methods, and statistical analysis methods. In addition,
      the guidelines suggest helpful presentations of data and important elements to
      include in discussions. The goal of these guidelines is to encourage transparent
      and complete reporting so that the relevant information will be available to
      others to help them to judge the usefulness of the data and understand the
      context in which the conclusions apply.

PMID- 16106246
TI  - Mortality following development of breast cancer while using oestrogen or
      oestrogen plus progestin: a computer record-linkage study.
AB  - The literature on the relationship between breast cancer mortality and
      postmenopausal oestrogen and combined oestrogen/progestin therapy is seemingly
      contradictory. This study explored survival after exposure to oestrogen or
      oestrogen plus progestin at or in the year prior to breast cancer diagnosis.
      Information on patients first diagnosed with invasive breast cancer between 1993
      and 1998 was linked with outpatient pharmacy data from 1992 to 2000. Patients
      were classified according to use of oestrogen alone or oestrogen plus progestin
      at or in the year prior to diagnosis. Compared to nonusers, and adjusting for age
      at diagnosis, race/ethnicity, tumour size and grade, oestrogen receptor status,
      surgery status, and chemotherapy and hormone therapy for breast cancer treatment,
      oestrogen plus progestin users had lower all-cause mortality (stage I hazard
      ratio (HR) = 0.69, 95% confidence interval (CI)= 0.48-0.99; stage II HR = 0.53,
      95% CI = 0.39-0.72) and breast cancer mortality (stage I HR = 0.52, 95% CI = 0.26
      1.04; stage II HR = 0.69, 95% CI = 0.48-0.98). Oestrogen users experienced little
      or no survival benefit for all-cause mortality (stage I HR = 1.04, 95% CI = 0.77
      1.42; stage II HR = 0.86, 95% CI = 0.65-1.14) or breast cancer mortality (stage I
      HR = 1.23, 95% CI 0.72-2.10; stage II HR = 1.01, 95% CI 0.72-1.41). Our findings
      suggest, relative to nonusers, a lower risk of death from all causes and from
      breast cancer in patients who were diagnosed with breast cancer while exposed to
      oestrogen plus progestin, but not in patients exposed to oestrogen only.

PMID- 16106247
TI  - Clinical features of colorectal cancer before diagnosis: a population-based case
      control study.
AB  - Most colorectal cancers are diagnosed after the onset of symptoms. However, the
      risk of colorectal cancer posed by particular symptoms is largely unknown,
      especially in unselected populations like primary care. This was a population
      based case-control study in all 21 general practices in Exeter, Devon, UK, aiming
      to identify and quantify the prediagnostic features of colorectal cancer. In
      total, 349 patients with colorectal cancer, aged 40 years or more, and 1744
      controls, matched by age, sex and general practice, were studied. The full
      medical record for 2 years before diagnosis was coded using the International
      Classification of Primary Care-2. We calculated odds ratios for variables
      independently associated with cancer, using multivariable conditional logistic
      regressions, and then calculated the positive predictive values of these
      variables, both individually and in combination. In total, 10 features were
      associated with colorectal cancer before diagnosis. The positive predictive
      values (95% confidence interval) of these were rectal bleeding 2.4% (1.9, 3.2);
      weight loss 1.2% (0.91, 1.6); abdominal pain 1.1% (0.86, 1.3); diarrhoea 0.94%
      (0.73, 1.1); constipation 0.42% (0.34, 0.52); abnormal rectal examination 4.0%
      (2.4, 7.4); abdominal tenderness 1.1% (0.77, 1.5); haemoglobin <10.0 g dl(-1)
      2.3% (1.6, 3.1); positive faecal occult bloods 7.1% (5.1, 10); blood glucose >10
      mmol l(-1) 0.78% (0.51, 1.1): all P < 0.001. Earlier diagnosis of colorectal
      cancer may be possible using the predictive values for single or multiple
      symptoms, physical signs or test results.

PMID- 16106248
TI  - Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours.
AB  - We reviewed the European Group for Blood and Marrow Transplantation (EBMT)
      experience with salvage high-dose chemotherapy (HDC) in paediatric patients with
      extragonadal germ-cell tumour (GCT). A total of 23 children with extragonadal
      GCT, median age 12 years (range 1-20), were treated with salvage HDC with
      haematopoietic progenitor cell support. The GCT primary location was intracranial
      site in nine cases, sacrococcyx in eight, retroperitoneum in four, and
      mediastinum in two. In all, 22 patients had a nongerminomatous GCT and one
      germinoma. Nine patients received HDC in first- and 14 in second- or third
      relapse situation. No toxic deaths occurred. Overall, 16 of 23 patients (70%)
      achieved a complete remission. With a median follow-up of 66 months (range 31-173
      months), 10 (43%) are continuously disease-free. Of six patients who had a
      disease recurrence after HDC, one achieved a disease-free status with surgical
      resection followed by chemotherapy and radiotherapy. In total, 11 patients (48%)
      are currently disease-free. Eight of 14 patients (57%) with extracranial primary
      and three of nine patients (33%) with intracranial primary GCT are currently
      disease-free. HDC induced impressive long-term remissions as salvage treatment in
      children with extragonadal extracranial GCTs. Salvage HDC should be investigated
      in prospective trials in these patients.

PMID- 16106249
TI  - Second primary malignancies after treatment for malignant lymphoma.
AB  - To determine the incidence and possible causes of second primary malignancies
      after treatment for Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL). A cohort
      of 3764 consecutive patients diagnosed with HL or NHL between January 1970 and
      July 2001 was identified using the Sheffield Lymphoma Group database. A search
      was undertaken for all patients diagnosed with a subsequent primary malignancy.
      Two matched controls were identified for each case. Odds ratios were calculated
      to detect and quantify any risk factors in the cases compared to their matched
      controls. Mean follow-up for the cohort was 5.2 years. A total of 68 patients who
      developed second cancers at least 6 months after their primary diagnosis were
      identified, giving a crude incidence of 1.89% overall: 3.21% among the patients
      treated for HL, 1.32% in those treated for NHL. Most common were bronchial,
      breast, colorectal and haematological malignancies. High stage at diagnosis
      almost reached statistical significance in the analysis of just the NHL patients
      (odds ratio = 3.48; P = 0.068) after adjustment for other factors. Treatment
      modality was not statistically significant in any analysis. High stage at
      diagnosis of NHL may be a risk factor for developing a second primary cancer.

PMID- 16106250
TI  - Adenovirus-mediated interferon alpha gene transfer induces regional direct
      cytotoxicity and possible systemic immunity against pancreatic cancer.
AB  - We previously demonstrated a characteristically high sensitivity of pancreatic
      cancer cells to interferon alpha (IFN-alpha) gene transfer, which induced a more
      prominent growth suppression and cell death in pancreatic cancer cells than in
      other types of cancers and normal cells. The IFN-alpha protein can exhibit both
      direct cytotoxicity and indirect immunological antitumour activity. Here, we
      dissected and examined the two mechanisms, taking advantage of the fact that IFN
      alpha did not show any cross-species activity in its in vivo effect. When a human
      IFN-alpha adenovirus was injected into subcutaneous xenografts of human
      pancreatic cancer cells in nude mice, tumour growth was significantly suppressed
      due to cell death in an adenoviral dose-dependent manner. The IFN-alpha protein
      concentration was markedly increased in the injected subcutaneous tumour, but
      leakage of the potent cytokine into the systemic blood circulation was minimal.
      When a mouse IFN-alpha adenovirus was injected into the same subcutaneous tumour
      system, all mice showed significant tumour inhibition, an effect that was
      dependent on the indirect antitumour activities of IFN-alpha, notably a
      stimulation of natural killer cells. Moreover, in this case, tumour regression
      was observed not only for the injected subcutaneous tumours but also for the
      untreated tumours at distant sites. This study suggested that a local IFN-alpha
      gene therapy is a promising therapeutic strategy for pancreatic cancer, due to
      its dual mechanisms of antitumour activities and lack of significant toxicity.

PMID- 16106251
TI  - TSPY is a cancer testis antigen expressed in human hepatocellular carcinoma.
AB  - In search for genes associated with hepatocellular carcinoma (HCC) by cDNA
      microarray, we found that the transcription of TSPY, 'testis-specific protein Y
      encoded', was upregulated in HCC. Investigation of a broad spectrum of normal and
      malignant tissues by RT-PCR revealed the TSPY transcript selectively expressed in
      normal testis, different histological types of human neoplastic tissues, and
      tumour cell lines. The expression of TSPY in cancer cells was further confirmed
      by in situ hybridisation. Indirect immunofluorescence microscopy analysis showed
      that TSPY was localised mainly in the cytoplasm of transiently transfected cells.
      Testis-specific protein Y-encoded was detected in 50% (16 of 32) of well- and
      moderately differentiated HCC patients, in 16% (four of 25) of poorly
      differentiated HCC patients, and in 5% (one of 19) of renal cell cancer patients.
      A serological survey revealed that 6.6% (seven of 106) HCC patients had anti-TSPY
      antibody response, demonstrating the immunogenicity of TSPY in humans. In
      conclusion, these data suggest that TSPY is a novel cancer/testis (CT) antigen
      and may be a potential candidate in vaccine strategy for immunotherapy in HCC
      patients.

PMID- 16106252
TI  - UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas.
AB  - The hybridisation of an Affymetrix HG_U95Av2 oligonucleotide array with RNAs
      extracted from six human thyroid carcinoma cell lines and a normal human thyroid
      primary cell culture led us to the identification of the UbcH10 gene that was
      upregulated by 150-fold in all of the carcinoma cell lines in comparison to the
      primary culture cells of human normal thyroid origin. Immunohistochemical studies
      performed on paraffin-embedded tissue sections showed abundant UbcH10 levels in
      thyroid anaplastic carcinoma samples, whereas no detectable UbcH10 expression was
      observed in normal thyroid tissues, in adenomas and goiters. Papillary and
      follicular carcinomas were only weakly positive. These results were further
      confirmed by RT-PCR and Western blot analyses. The block of UbcH10 protein
      synthesis induced by RNA interference significantly reduced the growth rate of
      thyroid carcinoma cell lines. Taken together, these results would indicate that
      UbcH10 overexpression is involved in thyroid cell proliferation, and may
      represent a marker of thyroid anaplastic carcinomas.

PMID- 16106253
TI  - The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal
      cancers.
AB  - There is increased incidence of microsatellite instability (MSI) in patients who
      develop multiple primary colorectal cancers (CRC), although the association with
      hereditary nonpolyposis colon cancer (HNPCC) is unclear. This study aims to
      evaluate the underlying genetic cause of MSI in these patients. Microsatellite
      instability was investigated in 111 paraffin-embedded CRCs obtained from 78
      patients with metachronous and synchronous cancers, and a control group
      consisting of 74 cancers from patients with a single CRC. Tumours were classified
      as high level (MSI-H), low level (MSI-L) or stable (MSS). MLH1, MSH2 and MSH6
      gene expression was measured by immunohistochemistry. Methylation of the MLH1
      promoter region was evaluated in MSI-H cancers that failed to express MLH1, and
      mutational analysis performed in MSI-H samples that expressed MLH1, MSH2 and MSH6
      proteins. The frequency of MSI-H was significantly greater in the multiple, 58
      out of 111 (52%), compared to the single cancers, 10 out of 74 (13.5%), P < 0.01.
      Of the 32 patients from whom two or more cancers were analysed, eight (25%)
      demonstrated MSI-H in both cancers, 13 (41%) demonstrated MSI-H in one cancer and
      11 (34%) failed to demonstrate any MSI-H. MSI-H single cancers failed to express
      MLH1 or MSH2 in seven out of nine (78%) cases and MSI-L/MSS cancers failed to
      express MLH1 or MSH2 in one out of 45 (2.2%) cases, all cancers expressed MSH6.
      MSI-H multiple cancers failed to express MLH1 or MSH2 in 21 out of 43 (48%) cases
      and MSI-L/MSS cancers failed to express MLH1 or MSH2 in four out of 32 (12.5%)
      cases. MSH6 expression was lost in five MSI-H multiple cancers, four of which
      also failed to express MLH1 or MSH2. Loss of expression of the same mismatch
      repair (MMR) gene was identified in both cancers from six out of 19 (31%)
      patients. Methylation was identified in 11 out of 17 (65%) multiple and three out
      of six (50%) single MSI-H cancers that failed to express MLH1. Mutational
      analysis of 10 MSI-H multiple cancers that expressed MLH1, MSH2 and MSH6 failed
      to demonstrate mutations in the MLH1 or MSH2 genes. We suggest that, although MSI
      H is more commonly identified in those with multiple colorectal cancers, this
      does not commonly arise from a classical HNPCC pathway.

PMID- 16106254
TI  - Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk.
AB  - IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation
      response by binding to IL1 receptors, and as a consequence inhibits the action of
      proinflammatory cytokines IL1alpha and IL1beta. In this study, we hypothesise
      that sequence variants in the IL1-RN gene are associated with prostate cancer
      risk. The study population, a population-based case-control study in Sweden,
      consisted of 1383 prostate cancer case patients and 779 control subjects. We
      first selected 18 sequence variants covering the IL1-RN gene and genotyped these
      single-nucleotide polymorphisms (SNPs) in 96 control subjects. Gene-specific
      haplotypes of IL1-RN were constructed and four haplotype-tagging single
      nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263
      and rs315951) that could uniquely describe >95% of the haplotypes. All study
      subjects were genotyped for the four htSNPs. No significant difference in
      genotype frequencies between cases and controls were observed for any of the four
      SNPs based on a multiplicative genetic model. Overall there was no significant
      difference in haplotype frequencies between cases and controls; however, the
      prevalence of the most common haplotype (ATGC) was significantly higher among
      cases (38.7%) compared to controls (33.5%) (haplotype-specific P = 0.009).
      Evaluation of the prostate cancer risk associated with carrying the 'ATGC'
      haplotype revealed that homozygous carriers were at significantly increased risk
      (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2-2.2), compared to
      noncarriers, while no significant association was found among subjects
      heterozygous for the haplotype (OR = 1.0, 95% CI = 0.8-1.2). Restricting analyses
      to advanced prostate cancer strengthened the association between the 'ATGC'
      haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95% CI
      = 1.3-2.5). In conclusion, the results from this study support the hypothesis
      that inflammation has a role of in the development of prostate cancer, but
      further studies are needed to identify the causal variants in this region and to
      elucidate the biological mechanism for this association.

PMID- 16106256
TI  - Association of the TSHR gene with Graves' disease: the first disease specific
      locus.
AB  - The development of autoimmune thyroid disease (AITD) is associated with
      autoantibodies directed against the thyroid stimulating hormone receptor (TSHR).
      Previous studies have failed to demonstrate a consistent association between the
      TSHR and AITD, or any of its sub-phenotypes. In the present study, we analysed
      the linkage disequilibrium (LD) structure encompassing the TSHR, to identify LD
      'blocks' and SNPs, which capture the majority of intra-block haplotype diversity.
      The haplotype tagging SNPs, plus all common SNPs reported in previous studies
      were genotyped in 1,059 AITD Caucasian cases and 971 Caucasian controls. A
      haplotype, across two LD blocks, showed association (P<1 x 10(-6), OR 1.7) with
      Graves' disease (GD) but not autoimmune hypothyroidism (AIH). We replicated these
      findings by genotyping the most associated GD SNP, rs2268458, in a separate UK
      Caucasian cohort of 1,366 AITD cases and 1,061 controls (GD, P=2 x 10(-6), OR
      1.3; AIH, P=NS). These results in two independent Caucasian data sets suggest
      that the TSHR is the first replicated GD-specific locus meriting further fine
      mapping and functional analysis to identify the aetiological variants.

PMID- 16106257
TI  - Bootstrap model averaging in time series studies of particulate matter air
      pollution and mortality.
AB  - The consensus from time series studies that have investigated the mortality
      effects of particulate matter air pollution (PM) is that increases in PM are
      associated with increases in daily mortality. However, recently concerns have
      been raised that the observed positive association between PM and mortality may
      be an artefact of model selection due to multiple hypothesis testing. This
      problem arises when a number of models are investigated, but only the "best"
      model is reported and all subsequent inference is based on this model, ignoring
      the model selection process. In this paper, we introduce the use of the bootstrap
      as a means of addressing the problems of model selection in PM mortality time
      series studies. Using the bootstrap to perform inference about the effect of PM
      on mortality is a process based on a set of models rather than on a single model.
      It is shown that using the bootstrap to overcome the problems of model selection
      is competitive with the existing methodology of Bayesian model averaging.

PMID- 16106258
TI  - Biomonitoring of chromium for residents of areas with a high density of
      electroplating factories.
AB  - The high density of electroplating factories in the geographic middle of Taiwan
      has prompted concern over the potential for exposure to harmful metals. The
      present study aimed to determine the levels of chromium in whole blood (B-Cr) of
      residents living in the high vs. low factory-density areas, and to examine the
      relations to gender and age. A total of 660 residents who had not moved within
      the 5 years preceding the study were sampled according to the stratified random
      sampling approach, at ages 35-44, 45-54, and 55-64 years, for both genders.
      Chromium determinations (n=641) were made using a graphite furnace atomic
      absorption spectrometer. The geometric mean (95% C.I.) of B-Cr was 0.357 (0.34
      0.38) microg/l. The International Federation of Clinical Chemistry (IFCC)
      nonparametric 0.95 reference limits of B-Cr was estimated to be <0.905 microg/l.
      B-Cr levels decreased with increasing age. Subjects in the areas with a high
      density (0.38 microg/l, 95% C.I.: 0.36-0.40) of electroplating factories had
      significantly higher B-Cr levels, compared to residents of the low-density (0.27,
      0.25-0.30) areas and to the general population from western countries. The health
      significance of the elevated B-Cr remains to be determined.

PMID- 16106259
TI  - Monitoring genetic diversity in tropical trees with multilocus dominant markers.
AB  - Since no universal codominant markers are currently available, dominant genetic
      markers, such as amplified fragment length polymorphism (AFLP), are valuable
      tools for assessing genetic diversity in tropical trees. However, the measurement
      of genetic diversity (H) with dominant markers depends on the frequency of null
      homozygotes (Q) and the fixation index (F) of populations. While Q can be
      estimated for AFLP loci, F is less accessible. Through a modelling approach, we
      show that the monolocus estimation of genetic diversity is strongly dependent on
      the value of F, but that the multilocus diversity estimate is surprisingly robust
      to variations in F. The robustness of the estimate is due to a mechanistic effect
      of compensation between negative and positive biases of H by different AFLP loci
      exhibiting contrasting frequency profiles of Q. The robustness was tested across
      contrasting theoretical frequency profiles of Q and verified for 10 neotropical
      species. Practical recommendations for the implementation of this analytical
      method are given for genetic surveys in tropical trees, where such markers are
      widely applied.

PMID- 16106260
TI  - Wolbachia variant that induces two distinct reproductive phenotypes in different
      hosts.
AB  - Wolbachia is an intracellular endosymbiont that induces a variety of reproductive
      alterations in diverse arthropods. The almond moth, Cadra cautella, is double
      infected with two Wolbachia variants, wCauA and wCauB, and expresses complete
      cytoplasmic incompatibility (CI). The individual contribution of wCauA and wCauB
      to the expression of CI are unclear, however, because the two variants have not
      been separated in this host. The effect of wCauA is of particular interest
      because it induces male killing when transferred into the Mediterranean flour
      moth, Ephestia kuehniella. In the present study, we generated C. cautella
      infected with only wCauA by treating double-infected insects with tetracycline.
      Single-infected C. cautella exhibited strong CI, demonstrating that wCauA induces
      two distinct reproductive phenotypes in different hosts: CI in C. cautella and
      male killing in E. kuehniella. CI was also observed in the cross of double
      infected males and single-infected females. Comparison of the single- and double
      infected insects by real-time quantitative polymerase chain reaction suggested
      that the wCauA density is not affected much by the presence or absence of wCauB.

PMID- 16106261
TI  - Conservation genetics of amphibians.
AB  - Amphibians are good models for investigating the genetics of wild animal
      populations because they are: (1) widely distributed in most ecosystems; (2) easy
      to sample in breeding assemblages; (3) often philopatric to breeding sites,
      generating high levels of population genetic structure; (4) amenable to
      controlled crossings in the laboratory; and (5) of major conservation concern.
      Neutral genetic markers, mostly microsatellites, have been used successfully in
      studies of amphibian effective population sizes and structures, and in assessing
      the consequences of hybridisation. Phylogeography has provided important insights
      into population histories and the fates of introductions. Quantitative genetic
      methods have demonstrated adaptive variation in life history traits of importance
      to fitness and therefore to population viability.

PMID- 16106262
TI  - Recent radiation in West African Taterillus (Rodentia, Gerbillinae): the
      concerted role of chromosome and climatic changes.
AB  - West African gerbils of the genus Taterillus constitute a complex of seven
      sibling species distributed from sudano-guinean to saharo-sahelian regions. They
      display radically rearranged karyotypes despite low genic divergence and a very
      recent differentiation, that is, within the last 0.4 Myr for the six most derived
      species. We here provide a comparison of the seven specific karyotypes and
      perform a cladistic analysis using chromosomal rearrangements character states.
      When a posteriori polarized mutations were mapped onto the phylogenetic tree, 38
      rearrangements were identified as fixed during the evolution of these rodents.
      This makes Taterillus one of the most striking examples of accelerated
      chromosomal evolution within placental mammals. Taking into account the types of
      chromosomal changes involved, divergence times between lineages, genetic
      distances, as well as reassessed geographic distributions, we suggest that (1)
      speciation in West African Taterillus was driven by chromosomal changes, and (2)
      the paleoclimatic oscillations of the Sahara desert have played a major role in
      their evolution. In particular, elevated plasticity of the Taterillus genome, as
      suggested by the patterns observed for some repetitive elements, would have led
      to a higher probability of mutation. We hypothesize that the process underpinning
      cladogenesis most probably involved highly underdominant genomic rearrangements
      that were fixed following pronounced populational bottlenecks resulting from
      drastic climatic and subsequent environmental changes. Major African rivers
      formed significant barriers to dispersal, limiting expansion during the more
      moist and so favorable periods. This scenario would explain the current
      parapatric species distributions and their relationship to the West African
      hydrographic features.

PMID- 16106263
TI  - Plasma coagulation factor VII activity and its correlates in healthy men.
AB  - OBJECTIVE: The aim of this study was to investigate the plasma coagulation factor
      VII activity and its correlates in healthy Australian men. DESIGN: Cross
      sectional study. SETTING: Free living subjects. SUBJECTS: A total of 139 healthy
      Australian males aged 20-55 y with widely varying intakes of individual fatty
      acids. OUTCOME MEASURES: The concentration of phospholipid fatty acids and the
      parameters of biochemistry were analysed by standard methods. Citrated plasma
      factor VII activity was measured by using the ACL 200 system with commercially
      available kits. RESULTS: In the stepwise multiple regression, controlled for age,
      body mass index and dietary groups, the two most important variables of factor
      VII activity were selected in the forward entry model with R (2) = 0.474 and P <
      0.0001 from 19 independent variables, which were significantly correlated with
      plasma factor VII activity in age-adjusted bivariate analysis where significance
      was considered at P < 0.01. Plasma factor VII activity was strongly negatively
      correlated with prothrombin time (PT) (Std. Coeff. -0.550), and significantly
      positively correlated with plasma phospholipid (PL) stearic acid (Std. Coeff.
      0.285). CONCLUSIONS: Increased factor VII activity was associated with shortening
      of PT. All types of fatty-acid concentrations of PLs were significantly
      positively correlated with factor VII activity; however, stearic acid was more
      potent than other fatty acids in healthy Australian men. SPONSORSHIP: Meat
      Research Corporation of Australia.

PMID- 16106264
TI  - Relations between high ponderal index at birth, feeding practices and body mass
      index in infancy.
AB  - OBJECTIVE: We compared feeding practices between infants of high ponderal index
      (PI) at birth (PI above the 90th percentile) and normal PI at birth (PI between
      10th and 90th percentiles), and examined how birth size and infant feeding
      practices were related to body mass index (BMI) at 12 months. DESIGN: In a cohort
      of 3000 infants invited to participate in a national Norwegian dietary survey,
      1825 participated both at 6 and 12 months of age, and the present study included
      those born full term and with a PI (weight/length3) at birth > or =10th
      percentile (n=1441). Data on feeding practices were collected by food-frequency
      questionnaires, and anthropometrical data were measured by health-care personnel.
      RESULTS: A lower proportion of infants born with high PI were exclusively
      breastfed for at least 4 months compared with infants born with normal PI (37 and
      47%, respectively; P=0.03). Earlier introduction of solid foods and higher
      consumption of some foods were also observed among infants of high PI. In a
      multivariate analysis, adjusted mean BMI (kg/m2) at 12 months was higher for
      infants of high PI at birth than for infants of normal PI (17.6 and 17.0,
      respectively; P<0.001) and higher for infants exclusively breastfed <3 months
      than for infants exclusively breastfed > or =3 months (17.5 and 17.2,
      respectively; P=0.001). CONCLUSIONS: High PI at birth was associated with a
      shorter duration of exclusive breastfeeding. Furthermore, high PI at birth and
      short-term exclusive breastfeeding were both associated with higher BMI at 12
      months.

PMID- 16106265
TI  - Site-specific occurrence of nonmelanoma skin cancers in patients with cutaneous
      melanoma.
AB  - In a registry-based case-control study, we compared the site-specific occurrence
      of nonmelanoma (keratinocytic) skin cancers among patients with cutaneous
      melanoma cases (cases, n = 3774) and solid tumours (controls, n = 349,923),
      respectively. Overall, patients with melanoma were almost five-fold more likely
      to develop keratinocytic cancers compared with solid tumour controls (adjusted OR
      4.7, 95% CI 4.1-5.3), but the risks varied depending upon the site of melanoma.
      Whereas patients with melanoma of the head and neck had similarly increased risks
      of keratinocytic cancers across all body sites, patients with melanoma of the
      trunk were significantly more likely to develop keratinocyte cancer diagnosed on
      the trunk (adjusted OR 12.5, 95% CI 7.2-20.2) than on the head and neck (adjusted
      OR 3.0, 95% CI 2.2-4.3). Similar colocalisation of skin tumours was observed for
      patients with melanomas of the lower limb. These findings provide support for the
      hypothesis that skin cancers at different anatomical sites may arise through
      different causal pathways.

PMID- 16106266
TI  - Treatment of hepatocellular carcinoma with major portal vein thrombosis by
      combined therapy with subcutaneous interferon-alpha and intra-arterial 5
      fluorouracil; role of type 1 interferon receptor expression.
AB  - We previously reported the beneficial effects of combination therapy of
      interferon (IFN)-alpha/5-fluorouracil (FU) for advanced hepatocellular carcinoma
      (HCC) with tumour thrombi in the major portal branches. This report describes the
      results of longer follow-up and includes more than double the number of patients
      relative to the original report, and evaluates the role of IFN-alpha/type 2
      interferon receptor (IFNAR2) expression on the response to the combination
      therapy. The study subjects were 55 patients with advanced HCC and tumour thrombi
      in the major branches of the portal vein (Vp3 or 4). They were treated with at
      least two courses of IFN-alpha/5-FU without major complication. In the 55
      patients, 24 (43.6%) showed objective response (eight (14.5%) showed complete
      response, 16 (29.1%) partial response), four (7.3%) showed no response, and 27
      (49.1%) showed progressive disease. Immunohistochemically, IFNAR2 expression was
      detected in nine out of 13 (69.2%) patients. There was significant difference in
      the time-to-progression survival (P = 0.0002) and the overall survival (P <
      0.0001) between IFNAR2-positive and -negative cases. There was a significant
      correlation between IFNAR2 expression and response to IFN-alpha/5-FU combination
      therapy in univariate analysis (P = 0.0070). IFN-alpha/5-FU combination therapy
      is a promising modality for advanced HCC with tumour thrombi in the major portal
      branches and could significantly depend on IFNAR2 expression.

PMID- 16106267
TI  - Comparison of HER-2 overexpression in primary breast cancer and metastatic sites
      and its effect on biological targeting therapy of metastatic disease.
AB  - HER-2 overexpression, a predictive marker of tumour aggressiveness and
      responsiveness to therapy, occurs in 20-30% of breast cancer. Although breast
      cancer is a heterogeneous disease, HER-2 measurement is carried out in primary
      tumour. This study aims to evaluate HER-2 overexpression in primary and
      metastases and its effect on treatment decisions. Biopsies from primary breast
      cancer and corresponding metastases from 58 patients were studied. HER-2
      overexpression was evaluated immunohistochemically in all primary and metastatic
      sites. Positive overexpression in primary and/or metastases was confirmed by
      fluorescence in situ hybridisation (FISH). Discordance in HER-2 overexpression
      between primary and metastatic sites was 14% (eight of 58 patients). Concordance
      was found in 50 (86%) of patients (95% CI: 77-95). In one patient (2%), HER-2 was
      negative in metastasis but positive in primary. In seven (12%) patients, HER-2
      was positive in metastases and negative in primary (95% CI: 3.7-20), and three of
      them responded to trastuzumab. Gene amplification by FISH was found in all cases
      with HER-2 positive (+2 and +3) by immunohistochemistry. Our data suggest that a
      possible discordance of HER-2 overexpression between primary and metastases
      should be considered when making treatment decisions in patients with primary HER
      2-negative tumours.

PMID- 16106269
TI  - Guest editorial: Breastfeeding and the public's health.

PMID- 16106268
TI  - Cervical human papillomavirus infection and squamous intraepithelial lesions in
      rural Gambia, West Africa: viral sequence analysis and epidemiology.
AB  - The development of effective strategies against cervical cancer in Africa
      requires accurate type specific data on human papillomavirus (HPV) prevalence,
      including determination of DNA sequences in order to maximise local vaccine
      efficacy. We have investigated cervical HPV infection and squamous
      intraepithelial lesions (SIL) in an unselected cohort of 1061 women in a rural
      Gambian community. Squamous intraepithelial lesions was diagnosed using cytology
      and histology, HPV was typed by PCR-ELISA of DNA extracts, which were also DNA
      sequenced. The prevalence of cervical HPV infection was 13% and SIL were observed
      in 7% of subjects. Human papillomavirus-16 was most prevalent and most strongly
      associated with SIL. Also common were HPV-18, -33, -58 and, notably, -35. Human
      papillomavirus DNA sequencing revealed HPV-16 samples to be exclusively African
      type 1 (Af1). Subjects of the Wolof ethnic group had a lower prevalence of HPV
      infection while subjects aged 25-44 years had a higher prevalence of cervical
      precancer than older or younger subjects. This first report of HPV prevalence in
      an unselected, unscreened rural population confirms high rates of SIL and HPV
      infection in West Africa. This study has implications for the vaccination of
      Gambian and other African populations in the prevention of cervical cancer.

PMID- 16106270
TI  - National Health and Medical Research Council Infant Feeding Guidelines for Health
      Workers, 2003.

PMID- 16106271
TI  - Benefits of breastfeeding.

PMID- 16106272
TI  - Describing breastfeeding practices in New South Wales using data from the NSW
      Child Health Survey, 2001.

PMID- 16106273
TI  - Factors affecting breastfeeding practices: applying a conceptual framework.
AB  - Knowledge about factors affecting breastfeeding can be developed by further
      research on underlying factors and by drawing out the implications and lessons
      from intervention research. The use of a conceptual framework to guide this
      research and the interpretation of results can help us to understand the relative
      importance of different factors, and how they interact, in turn, helping us to
      design effective interventions.

PMID- 16106274
TI  - Interventions to encourage and support breastfeeding.

PMID- 16106275
TI  - The NSW Health Breastfeeding Project.

PMID- 16106276
TI  - The Baby Friendly Hospital Initiative: a case study from NSW.

PMID- 16106277
TI  - The World Health Organization Code of Marketing of Breastmilk Substitutes and
      subsequent resolutions (The WHO Code).

PMID- 16106278
TI  - Communicable diseases report, NSW, for January and February 2005.

PMID- 16106279
TI  - The biggest yet: The 2004 report of the NSW Chief Health Officer.

PMID- 16106280
TI  - The National Public Health Performance Project: how do we know whether Australian
      public health services are performing?

PMID- 16106281
TI  - Development of a standardised regional report from the NSW Health Survey Program.

PMID- 16106282
TI  - Monitoring health behaviours and health status in NSW: release of the Adult
      Health Survey 2003.

PMID- 16106283
TI  - Delivering smoking cessation information in the workplace using Quit Online.

PMID- 16106284
TI  - Tobacco and health fact sheet: nicotine and other poisons.

PMID- 16106285
TI  - EpiReview: invasive pneumococcal disease, NSW, 2002.

PMID- 16106286
TI  - Communicable diseases report, NSW, for November and December 2004.

PMID- 16106287
TI  - Selective targeting of DNA for cleavage within DNA-histone assemblies by a
      spermine-[CpW(CO)3Ph]2 conjugate.
AB  - In contrast to the histone-modifying action of other complexes of the type
      CpML(n)R, the compound obtained by linking the phenyl rings of two CpW(CO)(3)Ph
      moieties to the DNA-binding agent spermine selectively cleaves DNA in DNA-histone
      assemblies.

PMID- 16106288
TI  - A new reactivity pattern for vinyl bromides: cine-substitution via palladium
      catalysed C-N coupling/Michael addition reactions.
AB  - Palladium catalysed C-N bond formation can be used to convert vinyl bromides to
      the corresponding enamines, which are reacted in situ with alkylidene malonates
      to provide Michael adducts. The overall transformation results in cine
      substitution of the starting vinyl bromide.

PMID- 16106289
TI  - Spin-labelled cyclodextrins as hosts for large supramolecular assemblies.
AB  - EPR spectroscopy was used to study formation of inclusion complexes of
      monofunctionalised spin-labelled beta-cyclodextrins; this method is very
      sensitive to the interactions of cyclodextrins with large guest molecules.

PMID- 16106290
TI  - First total synthesis of the biologically active 2,7-dioxygenated tricyclic
      carbazole alkaloids 7-methoxy-O-methylmukonal, clausine H (clauszoline-C),
      clausine K (clauszoline-J) and clausine O.
AB  - Using the iron-mediated arylamine cyclization as the key step we have achieved a
      short and highly efficient access to the biologically active 2,7-dioxygenated
      tricyclic carbazole alkaloids 7-methoxy-O-methylmukonal, clausine H (clauszoline
      C), clausine K (clauszoline-J) and clausine O.

PMID- 16106291
TI  - Rational design of new bifunctional inhibitors of type II dehydroquinase.
AB  - Selective inhibitors of type II dehydroquinase were rationally designed to
      explore a second binding-pocket in the active-site. The molecular modelling,
      synthesis, inhibition studies and crystal structure determination are described.

PMID- 16106292
TI  - Synthesis of achiral and racemic catenanes based on terpyridine and a
      directionalized terpyridine mimic, pyridyl-phenanthroline.
AB  - Concatenated macrocycles containing manisyl-substituted tridentate ligands
      2,2':6',2''-terpyridine and 2-pyridin-2-yl-1,10-phenanthroline (simply referred
      to as terpyridine and pyridyl-phenanthroline herein) have been prepared via dual
      cyclization procedures. The manisyl derivative (manisyl = 4-methoxy-2,6
      dimethylphenyl) was chosen for its ability to improve solubility while
      simultaneously incorporating functionality. Deprotection of the methoxy groups
      provided a soluble ligand that was re-alkylated with an array of terminal alkyne
      and alkene linkers. The tridentate coordinating ability of these ligands enabled
      complexation with Ru(ii) and Fe(ii), generating achiral and racemic octahedral
      complexes for terpyridine and pyridyl-phenanthroline, respectively. Subsequent
      macrocyclization via olefin metathesis or copper-mediated alkyne coupling
      afforded the corresponding catenanes, and in some cases a figure-eight
      macrocycle. The difference in symmetry and the presence of the manisyl group
      allowed the distinction between the catenane and the undesired figure-eight to be
      made directly by (1)H NMR. Metal-free achiral and racemic catenanes were obtained
      by liberating Fe(ii) from the octahedral bound title ligands by treatment with
      hydrogen peroxide.

PMID- 16106293
TI  - Structural and mechanistic studies on anthocyanidin synthase catalysed oxidation
      of flavanone substrates: the effect of C-2 stereochemistry on product selectivity
      and mechanism.
AB  - During the biosynthesis of the tricyclic flavonoid natural products in plants,
      oxidative modifications to the central C-ring are catalysed by Fe(ii) and 2
      oxoglutarate dependent oxygenases. The reactions catalysed by three of these
      enzymes; flavone synthase I, flavonol synthase and anthocyanidin synthase (ANS),
      are formally desaturations. In comparison, flavanone 3beta-hydroxylase catalyses
      hydroxylation at the C-3 pro-R position of 2S-naringenin. Incubation of ANS with
      the unnatural substrate (+/-)-naringenin results in predominantly C-3
      hydroxylation to give cis-dihydrokaempferol as the major product; trans
      dihydrokaempferol and the desaturation product, apigenin are also observed.
      Labelling studies have demonstrated that some of the formal desaturation
      reactions catalysed by ANS proceed via initial C-3 hydroxylation followed by
      dehydration at the active site. We describe analyses of the reaction of ANS with
      2S- and 2R-naringenin substrates, including the anaerobic crystal structure of an
      ANS-Fe-2-oxoglutarate-naringenin complex. Together the results reveal that for
      the 'natural' C-2 stereochemistry of 2S-naringenin, C-3 hydroxylation
      predominates (>9 : 1) over desaturation, probably due to the inaccessibility of
      the C-2 hydrogen to the iron centre. For the 2R-naringenin substrate,
      desaturation is significantly increased relative to C-3 hydroxylation (ca. 1 :
      1); this is probably a result of both the C-3 pro-S and C-2 hydrogen atoms being
      accessible to the reactive oxidising intermediate in this substrate. In contrast
      to the hydroxylation-elimination desaturation mechanism for some ANS substrates,
      the results imply that the ANS catalysed desaturation of 2R-naringenin to form
      apigenin proceeds with a syn-arrangement of eliminated hydrogen atoms and not via
      an oxygenated (gem-diol) flavonoid intermediate. Thus, by utilising flavonoid
      substrates with different C-2 stereochemistries, the balance between C-3
      hydroxylation or C-2, C-3 desaturation mechanisms can be altered.

PMID- 16106294
TI  - Enzymatic cyclizations of squalene analogs with threo- and erythro-diols at the
      6,7- or 10,11-positions by recombinant squalene cyclase. Trapping of carbocation
      intermediates and mechanistic insights into the product and substrate
      specificities.
AB  - In order to trap the carbocation intermediates formed during the squalene
      cyclization cascade, squalene analogs with threo- and erythro-diols at the 6,7-
      and 10,11-positions were incubated with the recombinant squalene cyclase from
      Alicyclobacillus acidocaldarius, leading to the construction of the triterpenes
      with tetrahydropyran, octahydrochromene, decahydronaphthalene with a carbonyl
      group, dodecahydrobenzo[f]chromene, tetradecahydronaphtho[2,1-b]oxepine and
      malabaricane skeletons, almost of which are novel compounds. These products
      indicate that 6-membered monocyclic, 6/6-fused bicyclic and 6/6/5-fused tricyclic
      cations were involved in the cyclization reaction in addition to acyclic cation.
      All the trapped cations were the stable tertiary cation, but not the secondary
      one, indicating that the polycyclization reaction proceeds with a Markovnikov
      closure. The product profiles revealed that the cyclization reactions proceeded
      with the product and substrate specificities in addition to enantioselectivity.
      Mechanistic insight into the observed stereochemical specificities indicated that
      the pre-organized chair-conformation of squalene-diols is tightly constricted by
      the cyclase and a free motion or a conformational change is not allowed in the
      reaction cavity, thus, the substrate and product specificities are dominantly
      directed by the least motion of the nucleophilic hydroxyl group toward the
      intermediary carbocation; a small rotation of the hydroxyl group afforded the
      cyclization products in a good yield, but a large rotation of the hydroxyl group
      gave a marginal or no detectable amount of products.

PMID- 16106295
TI  - A phase-switch purification approach for the expedient removal of tagged reagents
      and scavengers following their application in organic synthesis.
AB  - In this paper we wish to report on a variety of expedient chemical
      transformations and purifications achieved via a generic "catch and release"
      methodology, based on a synthetically inert bipyridyl chelating tag that can be
      selectively captured with a resin-bound copper(II) species. Utilising this
      approach we are able to derive many of the same benefits associated with both
      solid phase synthesis and supported reagent methods.

PMID- 16106296
TI  - New 2+2, 3+3 and 4+4 macrocycles derived from 1,2-diaminocyclohexane and 2,6
      diformylpyridine.
AB  - Two new Schiff base macrocycles - a 4+4 condensation product and a meso-type 2+2
      condensation product - were obtained in a reaction of trans-1,2
      diaminocyclohexane and 2,6-diformylpyridine. Reduction of these compounds led to
      the corresponding 4+4 and 2+2 macrocyclic amines. The macrocycles were
      characterised by NMR spectroscopy and electrospray mass spectrometry. The
      symmetry and stereochemistry of these macrocycles, as well as of new 3+3 and 4+4
      diastereomers identified in solution, has been established. X-Ray structures of
      the 2+2 and 4+4 Schiff base macrocycles confirm the configurations determined on
      the basis of spectroscopic investigations. The crystal structures reveal that the
      centres of the square-shaped 4+4 macrocycles form channels as a result of
      columnar stacking.

PMID- 16106297
TI  - A stereoselective synthesis of 1,6-diphenyl-1,3,5-hexatrienes utilising 4,4,6
      trimethyl-2-vinyl-1,3,2-dioxaborinane as a two-carbon alkenyl building block.
AB  - A number of 1,6-diphenyl-1,3,5-hexatrienes of varying alkene geometries were
      stereoselectively prepared from just two starting materials: iodobenzene and
      4,4,6-trimethyl-2-vinyl-1,3,2-dioxaborinane via a series of Heck, Suzuki-Miyaura
      and stereocontrolled iododeboronation reactions. These results demonstrate how
      4,4,6-trimethyl-2-vinyl-1,3,2-dioxaborinane can be used as a genuine two-carbon
      vinyl-dianion building block in stereocontrolled polyene synthesis.

PMID- 16106298
TI  - Slow interconversion of enantiomeric conformers or atropisomers of anilide and
      urea derivatives of 2-substituted anilines.
AB  - N-Acylated 2-substituted anilines undergo slow Ar-N bond rotation, allowing in
      some cases isolation of enantiomeric or diastereoisomeric atropisomers and in
      others the determination of the rate of Ar-N bond rotation by NMR. 2-Iodoanilides
      bearing a branched N-substituent demonstrate sufficient enantiomeric stability to
      be resolvable, either by HPLC or by formation of diastereoisomeric lactanilide
      derivatives. For the first time, the rates of Ar-N rotation in 2-substituted N,N'
      diarylureas have been established: they mainly fall in the region of 50-70 kJ
      mol(-1) with a relatively weak dependence on substituent size.

PMID- 16106299
TI  - A straightforward approach towards thiazoles and endothiopeptides via Ugi
      reaction.
AB  - Endothiopeptides can easily be obtained via Ugi reaction using thio acids as acid
      components. If isonitriles with an acetal group are applied, the endothiopeptides
      can directly be converted into thiazoles using TMSCl-NaI under microwave
      irradiation.

PMID- 16106300
TI  - Wang-aldehyde resin as a recyclable support for the synthesis of alpha,alpha
      disubstituted amino acid derivatives.
AB  - Merrifield resin was functionalised with hydroxybenzaldehyde under microwave
      irradiation. The resultant resin was used as a means for immobilisation and
      activation of alpha-amino acid esters for alkylation reactions. Alpha,alpha
      disubstituted and cyclic amino acid esters were prepared in good yields.

PMID- 16106301
TI  - Amino acid-derived hydroxamic acids as chiral ligands in the vanadium catalysed
      epoxidation.
AB  - New sulfonamide-derived hydroxamic acids have been developed as chiral ligands
      for the V-catalysed asymmetric epoxidation, showing high reactivity at subzero
      temperatures and moderate to good enantioselectivity. The strong accelerating
      effect exhibited by the ligands of this type can be attributed to the sulfonamide
      functionality. A range of cinnamyl type allylic alcohols were epoxidised with up
      to 74% ee.

PMID- 16106302
TI  - Efficient synthesis of methyl lycotetraoside, the tetrasaccharide constituent of
      the tomato defence glycoalkaloid alpha-tomatine.
AB  - Branched oligosaccharide lycotetraose, beta-D-glucopyranosyl-(1-->2)-[beta-D
      xylopyranosyl-(1-->3)]-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranose, is a
      key constituent of many steroidal saponins, including glycoalkaloid alpha
      tomatine, which is involved in protection of plants from invading pathogens. A
      new synthesis of the methyl beta-lycotetraoside () is described. Key steps of the
      synthesis include two successive glycosylation reactions of disaccharide acceptor
      methyl (4,6-O-benzylidene-3-O-p-methoxybenzyl-beta-D-glucopyranosyl)-(1-->4)
      2,3,6-tri-O-benzyl-beta-D-galactopyranoside with readily available benzoylated
      trichloroacetimidates of alpha-D-glucopyranose and alpha,beta-D-xylopyranose.
      This scheme allows sequential glycosylation in one-pot on account of the
      convenient in situ removal of a p-methoxybenzyl protecting group under the acid
      conditions of the first glycosylation step. Following deprotection,
      tetrasaccharide was obtained in 19% yield over eight steps.

PMID- 16106303
TI  - Synthesis of 3,4-dihydro-2H-pyrans by hetero-Diels-Alder reactions of
      functionalized alpha,beta-unsaturated carbonyl compounds with N-vinyl-2
      oxazolidinone.
AB  - Cycloadditions of 3-aryl-2-benzoyl-2-propenenitriles and 3-phenylsulfonyl-3-buten
      2-one to N-vinyl-2-oxazolidinone proceed regio- and diastereoselectively yielding
      cis and trans diastereoisomers of 4-aryl-3,4-dihydro-2-(2-oxo-3-oxazolidinyl)-2H
      pyrans in 37-65% yield. Cycloadducts cis- were the major products. Reaction of 5
      arylidene-1,3-dimethylbarbituric acids with dienophile afforded mixtures of 2H
      pyrano[2,3-d]pyrimidine-2,4(3H)-diones trans and products resulted from an
      elimination of 2-oxazolidinone, in 50-52% yield. To confirm the experimental
      results, semiempirical AM1 and PM3 calculations of frontier orbital energies have
      been performed.

PMID- 16106304
TI  - Synthesis and spectroscopy of an oligophenyl based cruciform with remarkable pi
      pi assisted folding.
AB  - A facile route has been developed for the preparation of a new family of
      oligophenyls based on a 2,5,2',5'-tetra-aryl substituted biphenyl structural
      motif. The cruciform terphenyl dimer 2,5,2',5'-tetra(4-tert-butylphenyl)-1,1'
      biphenyl () has been prepared in a two step protocol as a representative of this
      interesting class of materials. The thermal behaviour of the cruciform was
      analysed by DSC and shows that forms an amorphous glass when cooled from the
      isotropic melt. Subsequent heating reveals a glass transition temperature at 130
      degrees C. X-Ray single crystal structure analysis of 2,2'-bis(4-tert
      butylphenyl)-1,1'-biphenyl () and shows that both these molecules with a quater
      phenyl substructure adopt a folded solid-state structure. Examining the (1)H NMR
      spectra of and reveals that the interactions that induce this folding in the
      solid-state are sufficiently strong to bias foldamer formation also in solution.
      Consequently, it is reasonable to assume that the folded conformation within the
      lattice is due to intramolecular pi-pi interaction rather than being imposed by
      crystal packing. The optical properties of the cruciform terphenyl dimer are
      discussed relative to the linear analogue 1,4-bis(4-tert-butylterphenyl)benzene
      ().

PMID- 16106305
TI  - Nitric oxide release from the unimolecular decomposition of the superoxide
      radical anion adduct of cyclic nitrones in aqueous medium.
AB  - Nitrones such as 5,5-dimethyl-1-pyrroline N-oxide (DMPO), 5-diethoxyphosphoryl-5
      methyl-1-pyrroline N-oxide (DEPMPO) and 5-ethoxycarbonyl-5-methyl-1-pyrroline N
      oxide (EMPO) have become the spin-traps of choice for the detection of transient
      radical species in chemical and biological systems using electron paramagnetic
      resonance (EPR) spectroscopy. The mechanism of decomposition of the superoxide
      radical anion (O2(.-)) adducts of DMPO, DEPMPO and EMPO in aqueous solutions was
      investigated. Our findings suggest that nitric oxide (NO) was formed during the
      decomposition of the O2(.-) adduct as detected by EPR spin trapping using Fe(II)N
      methyl-d-glucamine dithiocarbamate (MGD). Nitric oxide release was observed from
      the O2(.-) adduct formed from hypoxanthine-xanthine oxidase, PMA-activated human
      neutrophils, and DMSO solution of KO2. Nitric oxide formation was not observed
      from the independently generated hydroxyl radical adduct. Formation of nitric
      oxide was also indirectly detected as nitrite (NO2(.-)) utilizing the Griess
      assay. Nitrite concentration increases with increasing O2(.-) concentration at
      constant DMPO concentration, while NO2(.-) formation is suppressed at anaerobic
      conditions. Moreover, large excess of DMPO also inhibits NO2(.-) formation which
      can be attributed to the oxidation of DMPO to hydroxamic acid nitroxide (DMPO-X)
      by nitrogen dioxide (NO2), a precursor to NO2(.-). Product analysis was also
      conducted to further elucidate the mechanism of adduct decay using gas
      chromatography-mass spectrometry (GC-MS) technique.

PMID- 16106306
TI  - Synthesis and derivatisation of a novel spiro[1-benzofuran-2,4'-piperidin]-3-one
      scaffold.
AB  - The synthesis of a novel spiro[1-benzofuran-2,4'-piperidin]-3-one scaffold has
      been achieved in five steps with an overall yield of 47%. The versatility of the
      spiropiperidine scaffold in the context of library synthesis is exemplified by
      selective and sequential derivatisation of the amino and aryl bromide functional
      groups, including the development of multi-step telescope reaction matrices.

PMID- 16106307
TI  - A cytotoxic triketone-phloroglucinol-bullatenone hybrid from Lophomyrtus bullata.
AB  - Cytotoxic activity against the P388 cell line was seen in a crude extract of the
      New Zealand shrub Lophomyrtus bullata(Myrtaceae). Bioactivity-guided isolation
      led to a compound with NMR spectra complicated by the presence of two isomers.
      These crystallised together and an X-ray structure showed them to be
      stereoisomeric hybrids of triketone, phloroglucinol and bullatenone units. NMR
      measurements on the mixed isomers, as well as a cyclic ether produced from them
      by acid catalysed dehydration, were consistent with these structures. The natural
      products, named bullataketals A and B, have cytotoxic activity against the P388
      cell line (IC(50) 1 microg ml(-1)), and antimicrobial activity against Bacillus
      subtilis.

PMID- 16106308
TI  - [Blood lactate as prognostic marker in critically ill children: a problem related
      to production or clearance?].

PMID- 16106309
TI  - [Continuous glucose monitoring: a practice that should be explored].

PMID- 16106310
TI  - [Aerosols and spacers for acute asthma in children. Evolution and time to change
      the routine].

PMID- 16106311
TI  - [Clinical evaluation and treatment of insomnia in childhood].
AB  - OBJECTIVES: The aim of this article is to review and update the knowledge about
      insomnia in childhood. SOURCE OF DATA: The text was based on a MEDLINE search
      (publications from 1999 to 2004) using the keywords sleep disorders, insomnia,
      and childhood. Classic articles and textbooks about the subject were also
      included. The authors proposed a practical schedule to evaluate and treat
      insomnia in childhood. SUMMARY OF THE FINDINGS: The article was structured on
      descriptive topics containing the definition of insomnia, age-related clinical
      characteristics and therapeutics. CONCLUSIONS: Insomnia is a prevalent sleep
      disorder in pediatric outpatient clinics and is often misdiagnosed. Defining its
      etiology is the main goal to establish therapeutic procedures. In most cases,
      clinical history is sufficient to establish the diagnosis and reassure parents of
      the benign nature of this condition.

PMID- 16106312
TI  - [Blood lactate concentration as prognostic marker in critically ill children].
AB  - OBJECTIVE: To assess the use of lactate as a marker of tissue hypoperfusion and
      as a prognostic index in critically ill patients. METHODS: Prospective,
      longitudinal, observational study of 75 patients admitted to the pediatric ICU of
      Hospital de Clinicas of Universidade Federal do Parana, between November 1998 and
      May 1999. According to the lactate level on admission, patients were divided into
      group A (lactate > or = 18 mg/dl) and group B (lactate < 18 mg/dl). In terms of
      outcome, patients were classified into survivors and nonsurvivors. In group A,
      the clinical evaluation and the collection of arterial blood samples were
      performed on admission, at 6, 12, 24, 48 hours, and every 24 hours after that. In
      group B, they were carried out in the same way, but interrupted 48 hours after
      admission. RESULTS: Groups A and B consisted of 50 and 25 patients, respectively.
      Group A presented more clinical signs of hypoperfusion (24/50). There was a
      statistically significant difference regarding the mean lactate levels on
      admission between those patients who died within 24 hours of admission (95 mg/dl)
      and those who died 24 hours after admission (28 mg/dl). The lactate level at 24
      hours of admission revealed better sensitivity (55.6%) and specificity (97.2%) as
      a predictor of death. CONCLUSIONS: Most patients with lactate levels > or = 18
      mg/dl showed clinical signs of hypoperfusion on admission. The normalization or
      reduction of lactate levels at and after 24 hours of admission was significantly
      related with higher chances of survival.

PMID- 16106313
TI  - [Accuracy, utility and complications of continuous glucose monitoring system
      (CGMS) in pediatric patients with type 1 diabetes].
AB  - OBJECTIVE: To evaluate the accuracy, utility and complications of continuous
      glucose monitoring system in children and adolescents with type 1 diabetes.
      METHODS: This retrospective study assessed 16 type 1 diabetic patients (16.12+/
      4.41 years) submitted to continuous glucose monitoring system (Medtronic;
      Northridge, CA) for 72 hours. The following parameters were analyzed: mean
      capillary glucose level and mean glucose value measured by the continuous glucose
      monitoring system; glucose excursions (continuous glucose monitoring system vs.
      capillary glucose measurement), postprandial hyperglycemia (NR < 140 mg/dl),
      nocturnal hypoglycemia, complications (trauma, local infection, disconnection)
      and therapeutic management after continuous glucose monitoring. A1c levels were
      measured at the beginning and after 3 months of the study. RESULTS: The mean
      capillary glucose values were 214.3+/-66.5 mg/dl vs. 207.6+/-54.6 mg/dl by
      continuous glucose monitoring system, with a significant correlation (p = 0.001).
      The correlation coefficient and mean absolute error were 0.86+/-0.21 and 12.6% of
      the median, respectively. The continuous glucose monitoring system was
      significantly more efficient in detecting glucose excursion than fingerstick
      capillary blood sampling (p = 0.04; W = 74), and postprandial hyperglycemia was
      identified in 60% of type 1 diabetic patients with a median value of 157 mg/dl (<
      140 mg/dl). Nocturnal hypoglycemia was detected in 46.7% of these patients. The
      evaluation of A1c levels in eight (50%) patients before continuous glucose
      monitoring and after 3 months showed a significantly lower level of A1c in this
      population (8.18+/-1.5 vs. 7.28+/-1.3; p = 0.034). The therapeutic management of
      type 1 diabetes was changed in 100% of patients. No complications were detected
      in 93.7% of patients. CONCLUSIONS: The continuous glucose monitoring system
      showed to be a very safe, well-tolerated and highly accurate method, with a low
      complication rate. It is a good method to identify glucose excursion and
      postprandial hyperglycemia, and to improve metabolic changes in therapeutic
      strategies, with a significant impact on the A1c levels of pediatric diabetic
      patients. The efficacy of the continuous glucose monitoring system in detecting
      hypoglycemia is still unclear in the medical literature.

PMID- 16106314
TI  - [Different inhaler devices in acute asthma attacks: a randomized, double-blind,
      placebo-controlled study].
AB  - OBJECTIVE: To verify the efficacy, side effects, and cost of treatment of acute
      asthma attacks, using different inhaler devices. METHODS: This is a randomized,
      double-blind, placebo-controlled study. Salbutamol was administered via a
      nebulizer, a metered-dose inhaler (attached to a commercially available spacer
      device), a homemade non-valved spacer device, or a dry powder inhaler.
      Assessments were made at zero, 20, 40 and 60 minutes, followed by the application
      of salbutamol and placebo with another device. Forty children (mean age of 11+/
      3.5 years) with acute asthma attacks, were evaluated. Clinical score, forced
      expiratory volume in one second and side effects were analyzed. The costs for
      medication and spacer devices were calculated. RESULTS: There is no difference
      between groups regarding clinical score and variation of forced expiratory volume
      in one second. There was a major variation in the heart rate response to the
      nebulizer (35%) compared to the commercially available spacer and dry powder
      inhaler (15 and 17%) and between the homemade spacer and the commercially
      available spacer (28 and 15%) (p = 0.004). The nebulizer and homemade spacer
      caused more tremor (p = 0.02). The cost of treatment was higher for the nebulizer
      and commercially available spacer (p = 0.0001). CONCLUSIONS: The nebulizer was
      more expensive and used more medicine, showing the same efficiency. The homemade
      spacer was cheaper, but presented more side effects. The commercially available
      spacer was as expensive as the nebulizer, although safer. The dry powder inhaler
      was cheaper, but, just as the homemade spacer, it also caused tachycardia.

PMID- 16106315
TI  - [Prevalence and severity of asthma among adolescents and their relationship with
      the body mass index].
AB  - OBJECTIVE: To investigate the relationship between the increase of body mass
      index and the prevalence and severity of asthma in adolescents from Santa Maria,
      in southern Brazil, and surrounding regions. METHOD: A cross-sectional,
      observational, population-based study was carried out with 4,010 schoolchildren
      aged 13 and 14 years, without any gender restrictions, who answered the written
      questionnaire of the International Study of Asthma and Allergies in Childhood
      (ISAAC) phase III. Body mass index was used (kg/m2) as recommended by the World
      Health Organization for the assessment of nutritional status: below the fifth
      percentile (underweight), at or above the fifth percentile and below the 85th
      percentile (normal weight), at or above the 85th percentile and below the 95th
      percentile (overweight), and at or above the 95th percentile (obesity). The
      relationship between body mass index and the prevalence and severity of asthma
      was analyzed using the chi-square test for trend (statistical significance: p <
      or = 0.05). RESULTS: There was a significant statistical association between the
      increase in body mass index and the prevalence of "wheezing ever" (p = 0.036),
      and "wheezing with exercise" (p = 0.008). When stratified by sex, there was a
      positive association just for "wheezing ever" (p = 0.028) for boys and "wheezing
      with exercise" (p = 0.03) for girls. CONCLUSION: The increase in body mass index
      was associated with the increase in the prevalence of wheezing ever, but not with
      the increase in the prevalence and severity of asthma among adolescents.

PMID- 16106316
TI  - [The influence of breastfeeding technique on the frequencies of exclusive
      breastfeeding and nipple trauma in the first month of lactation].
AB  - OBJECTIVE: To investigate the influence of breastfeeding technique on the
      frequencies of exclusive breastfeeding and nipple trauma in the first month of
      lactation. METHODS: We searched for unfavorable parameters of breastfeeding (five
      related to mother/baby positioning and three related to baby's latch on) in 211
      mother-baby pairs in the maternity ward and at day 30, at home. We compared the
      frequencies of these parameters between mothers practicing or not exclusive
      breastfeeding at days 7 and 30, and between mothers with or without nipple trauma
      at the hospital. RESULTS: The number of unfavorable parameters in the maternity
      ward was similar for mother-baby pairs practicing or not exclusive breastfeeding
      at day 7 and 30. However, at day 30, it was, on average, lower among those under
      exclusive breastfeeding, regarding positioning (1.7+/-1.2 vs 2.2+/-1.1; p =
      0.009) as well as latch on (1.0+/-0.6 vs 1.4+/-0.6; p < 0.001). The number of
      unfavorable parameters related to latch on in the maternity ward was similar for
      women with or without nipple trauma, but women without trauma presented a higher
      number of unfavorable parameters related to positioning. (2.0+/-1.4 vs 1.4+/-1.2;
      p = 0.04). CONCLUSIONS: The frequencies of exclusive breastfeeding in the first
      month and of nipple trauma were not influenced by the breastfeeding technique in
      the maternity ward, but there was an association between a better technique at
      day 30 and the practice of exclusive breastfeeding. New studies may help to
      elucidate whether an improvement in breastfeeding practices over time helps the
      maintenance of exclusive breastfeeding or whether the introduction of bottle
      feeding determines a negative effect on breastfeeding.

PMID- 16106317
TI  - [Nutritional status and intestinal iron absorption in children with chronic
      hepatic disease with and without cholestasis].
AB  - OBJECTIVE: To evaluate food intake, occurrence of energy-protein malnutrition and
      anemia, and intestinal iron absorption in children with chronic liver disease.
      METHODS: The study included 25 children with chronic liver disease, 14 with
      cholestasis and 11 without cholestasis. The age varied between 6.5 months and
      12.1 years. Intestinal iron absorption was evaluated by the increment of serum
      iron one hour after the ingestion of 1 mg/kg of elemental iron and by the
      response to oral iron therapy. Iron intestinal absorption was compared to a group
      with iron deficiency anemia (without liver disease). RESULTS: The mean intake of
      energy and protein in the cholestatic group was higher than in patients without
      cholestasis. The nutritional deficit was more severe in cholestatic patients,
      especially with regard to height-for-age and weight-for-age indices. Anemia was
      found in both cholestatic group (11/14; 78.6%) and noncholestatic group (7/11;
      63.6%). The cholestatic group presented lower (p < 0.05) intestinal iron
      absorption (90.6+/-42.1 microg/dl) than the iron deficiency anemia group (159.6+/
      69.9 microg/dl). However, cholestatic patients responded to oral iron therapy.
      The noncholestatic group showed intestinal iron absorption similar to the iron
      deficiency anemia group. CONCLUSION: The cholestatic group showed more severe
      nutritional deficits. Despite the evidence of lower iron intestinal absorption,
      cholestatic patients responded to oral iron therapy, probably, due to the
      coexistence of iron deficiency.

PMID- 16106318
TI  - [Nutritional status surveillance of children in a health district in southern
      Brazil].
AB  - OBJECTIVE: To investigate the nutritional status of children referred by a
      primary care center to the Nutritional Surveillance Program (Pra-Crescer), and to
      follow up children at risk in a health district of Porto Alegre. METHODS: A
      retrospective cohort study was conducted with 674 children, aged between 6 and 59
      months, referred to the Pra-Crescer Program. Height-for-age, weight-for-height
      and weight-for-age indices were used to evaluate nutritional status. The cutoff
      points were the 3rd and 10th percentiles of the NCHS standards. The nutritional
      status of 391 children at nutritional risk was followed up for 12 months. The chi
      square test was used to analyze associations between variables. RESULTS: Fifty
      eight percent of the children had nutritional deficit. Of these, 38.1% were
      undernourished (< P3), and 61.9% were at nutritional risk (between P3 and P10).
      Height-for-age deficit was the most frequent, and the age group mostly affected
      was 12 to 24 months. Among those at nutritional risk, 50.1% completed the follow
      up, 33.5% did not start follow-up, and 16.4% were lost to follow-up. 41.3 %
      recovered nutritional health, 10.2% showed some improvement, without correcting
      their anthropometric deficits. 39.8% did not show any improvement, and 8.7% had
      worsening of their deficits. Recovery of nutritional health occurred, on average,
      within 7.5 months. CONCLUSIONS: This study showed the importance of following up
      children at nutritional risk and indicates that some aspects should be improved
      in surveillance programs. Such improvements may reduce the number of children
      lost to follow-up.

PMID- 16106319
TI  - [Bone mineral density, milk intake and physical activity in boys who suffered
      forearm fractures].
AB  - OBJECTIVE: To compare boys with and without forearm fracture in terms of their
      bone mineral density, intake of milk and dairy products, and physical activity.
      METHODS: There were 23 boys in each group (aged between 7 and 13 years). They
      were submitted to bone densitometry with dual-energy x-ray absorptiometry (DEXA)
      of the forearm (opposite side of the fracture). Participants answered
      questionnaires about their intake of milk and dairy products, and about their
      physical activity. RESULTS: The mean+/-SD of the bone mineral density of the
      radial and ulnar distal diaphysis in the case group (0.430+/-0.038 g.cm(-2)) was
      significantly lower (p = 0.018) than that of the control group (0.458+/-0.039
      g.cm(-2)). Likewise, the mean of the distal metaphysis of the forearm was 0.309+/
      0.033 g.cm(-2) in the case group and 0.349+/-0.054 g.cm(-2) in the control group
      (p = 0.004). Milk intake (1.5+/-1.2 cups a day) was significantly lower in the
      case group (p = 0.001) than in the control group (2.7+/-1.2 cups a day). The
      number of boys who practiced after-school physical activity was significantly
      lower (p = 0.017) in the case group (six boys = 26%) than in the control group
      (15 boys = 53%). CONCLUSION: Boys who suffered forearm fracture showed lower bone
      mineral density compared with the control group. In the case group, milk intake
      and physical activity were lower than in the control group.

PMID- 16106320
TI  - [Bone mineral density in overweight and obese adolescents].
AB  - OBJECTIVE: To study bone density as a concomitant factor for obesity in post
      pubertal adolescents, controlling for other variables that may interfere in such
      a relation. METHODS: Study comprising 83 overweight and obese adolescents (BMI >
      or = P85) and 89 non obese ones (P5 < or = BMI < or = P85). Cases and controls
      were selected out of 1,420 students (aged 14-19) from a public school in the city
      of Sao Paulo. The bone mineral density of the lumbar spine (L2-L4 in g/cm2) was
      assessed by dual-energy x-ray absorptiometry (LUNARtrade mark DPX-L). The
      variable bone density was dichotomized using 1.194 g/cm2 as cutoff point.
      Bivariate analyses were conducted considering the prevalence of overweight and
      obesity followed by multivariate analysis (logistic regression) according to a
      hierarchical conceptual model. RESULTS: The prevalence of bone density above the
      median was twice more frequent among cases (69.3%) than among controls (32.1%).
      In the bivariate analysis such prevalence resulted in an odds ratio (OR) of 4.78.
      The logistic regression model showed that the association between obesity and
      mineral density is yet more intense with an OR of 6.65 after the control of
      variables related to sedentary lifestyle and intake of milk and dairy products.
      CONCLUSION: Obese and overweight adolescents in the final stages of sexual
      maturity presented higher bone mineral density in relation to their normal-weight
      counterparts; however, cohort studies will be necessary to evaluate the influence
      of such characteristic on bone resistance in adulthood and, consequently, on the
      incidence of osteopenia and osteoporosis at older ages.

PMID- 16106321
TI  - [Type 1 autoimmune hepatitis in children and adolescents: assessment of
      immunosuppressive treatment withdrawal].
AB  - OBJECTIVE: To assess treatment withdrawal in children and adolescents with
      autoimmune hepatitis, with clinical and laboratory remission for a minimum period
      of 24 months, determining the relapse rate after treatment withdrawal. METHODS:
      This is a descriptive, retrospective and partially prospective study of 21
      children and adolescents with type 1 autoimmune hepatitis treated at the
      Outpatient Division of Pediatric Hepatology, Teaching Hospital of Universidade
      Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil, between January 1986 and
      December 2001. RESULTS: We assessed 54 patients and selected 21, of whom 19 were
      female subjects (90.5%), aged between 5.7 and 17.6 years (median = 13.8 years),
      with a mean follow-up of 5.1+/-2.4 years (median = 4.4 years) and an average
      clinical and laboratory remission of 4.1+/-1.5 years (median = 4.1 years). Out of
      the 21 patients studied, 10 (47.6%) manifested some inflammatory activity that
      prevented the discontinuation of treatment, which was withdrawn in 11 patients
      (52.4%). Out of these, six patients (54.5%) presented reactivation of the disease
      and five maintained clinical and laboratory remission with a mean follow-up of
      4+/-1 years (median = 3.9 years). The time interval between discontinuation of
      treatment and reactivation of the disease ranged from 29 days to 40.3 months
      (median = 2.2 months). CONCLUSIONS: We observed a high relapse rate (54.5%) in
      this group of patients with autoimmune hepatitis, which was more frequent within
      the first 12 months after treatment withdrawal, in addition to a high number of
      patients that presented some degree of inflammatory activity despite the long
      period of clinical and laboratory remission.

PMID- 16106322
TI  - [Hypercalcemia and multiple osteolytic lesions in a child with disseminated
      paracoccidioidomycosis and pulmonary tuberculosis].
AB  - OBJECTIVE: To describe the case of a child with paracoccidioidomycosis who
      presented hypercalcemia with multiple osteolytic lesions. DESCRIPTION: A 6-year
      old boy was admitted with a one-month history of fever and hepatosplenomegaly. On
      admission, he looked sick, pale, and had disseminated lymphadenopathy and
      hepatosplenomegaly. The laboratory findings included anemia (hemoglobin = 6.8
      g/dl), eosinophilia (1,222/mm3), thrombocytopenia (102,000/mm3), and
      hypoalbuminemia (serum albumin = 2.2 g/dl). Paracoccidioides brasiliensis was
      identified in bone marrow examination. In the second week after admission, the
      patient presented joint pain, poor activity and difficulty in walking. He
      presented hypercalcemia (maximum value = 14.9 mg%) and reduction in renal
      function, which lasted for two weeks. On the 42nd day after admission, his chest
      X-ray showed lytic lesions in clavicle, scapula, ribs, and humerus, with
      bilateral slipped capital humeral epiphysis. The patient presented
      nephrocalcinosis and nephrolithiasis, reduction in creatinine clearance and
      evidence of tubular lesions. At the end of the second month after admission,
      Mycobacterium tuberculosis was isolated in gastric washing. The child received
      treatment for paracoccidioidomycosis and tuberculosis and has not had any
      sequelae for 3 years. COMMENTS: The development of symptomatic hypercalcemia
      leading to renal lesion, associated with multiple osteolytic lesions, had never
      been described in paracoccidioidomycosis. Although pulmonary tuberculosis was
      diagnosed and could be related to hypercalcemia, the sudden onset of
      hypercalcemia and its normalization without specific treatment for tuberculosis
      suggests that bone lysis was the most important factor in the genesis of
      hypercalcemia.

PMID- 16106324
TI  - [Is adrenaline inhalation safe?].

PMID- 16106325
TI  - Myocarditis: the immunologist's view on pathogenesis and treatment.
AB  - Viral myocarditis is a frequent and often unrecognised cause of post-inflammatory
      cardiomyopathy. The role of viral persistence and heart-specific autoimmunity in
      the development of myocarditis and heart failure is still controversial. This
      review updates the current view on the immunological mechanisms of disease
      development and addresses the current and future role of immunomodulation and
      immunosuppression as treatment options for defined subgroups of patients with
      myocarditis or dilated cardiomyopathy.

PMID- 16106326
TI  - What are disease perceptions and subjective treatment goals of insulin treated
      diabetic patients?
AB  - BACKGROUND: Despite increasing importance of patient self-management, little is
      known about their own perceptions and treatment goals. OBJECTIVES: The aim of
      this explorative study was to examine what diabetic patients perceive as most
      concerning and what their own treatment goals are. METHODS: A 23-item anonymous
      questionnaire was distributed among type 1 diabetic patients treated with and
      without an insulin pump and insulin treated type 2 diabetic patients in the
      outpatient clinic of a University Hospital. 86% of the questionnaires were
      returned (n = 124). RESULTS: In open-ended questions, patients in all three
      groups together felt mostly restricted by their loss of freedom (24%), the
      dietary restrictions (17%) and the need to measure blood glucose (17%). Patients
      treated with an insulin pump worried more about hypoglycaemia and less about
      dietary restrictions. In closed-ended questions, patients were mostly concerned
      about hypoglycaemia and developing complications. However, the main treatment
      goal of both groups together was long-term good blood glucose control (63%).
      Further patient goals were the prevention of complications (27%) and the
      preservation of a good quality of life. Quality of life was a more important goal
      for type 1 diabetic patients (29%) than for type 2 diabetic patients (0%).
      Patients thought that blood glucose control was more important for their
      physicians (main treatment goal for 86%) than for themselves. CONCLUSION: Insulin
      treated patients with diabetes spontaneously express concerns about their actual
      quality of life and daily hassles and mention long-term worries after explicit
      questioning. For their main treatment goals they choose mainly long-term goals.
      According to the patients, physicians tend to overestimate blood glucose control.

PMID- 16106327
TI  - Portal vein thrombosis (PVT): a study of 20 non-cirrhotic cases.
AB  - BACKGROUND: Portal and mesenteric venous thrombosis (PVT) is an uncommon disease
      with serious consequences if not discovered early in order to prevent
      complications such as variceal bleeding and intestinal ischaemia. The objective
      of this study was to describe the clinical presentation and outcome of patients
      with PVT with a view to early diagnosis and treatment of this disease. The study
      was restricted to patients with PVT not caused by underlying liver cirrhosis.
      PATIENTS AND METHODS: To analyse important clinical characteristics of this
      entity we performed a retrospective study of 20 non-cirrhotic patients seen in
      our hospital from February 1998 to March 2003. RESULTS: The main clinical symptom
      was abdominal pain (13 patients, 86%), sometimes in combination with diarrhoea
      and vomiting (5 patients, 33%), nausea and anorexia (3 patients). Laboratory
      signs were non-specific and diagnosis was usually by computed tomography (19
      patients, 95%). Causative factors included prothrombotic states (9 patients, 45%)
      and/or local factors (5 patients, 25%). Complications must be expected from
      portal hypertension (15 patients, 75%), which was associated with variceal
      bleeding in 6 patients (30%). Bowel ischaemia (5 patients, 25%) and bowel
      infarction (2 patients) were less frequent. Treatment consisted of immediate
      anticoagulation in almost all cases (18 patients, 90%), while invasive approaches
      were followed in selected patients. The prognosis of PVT was good in patients
      without a severe underlying disease (median followup 21 months). CONCLUSIONS: In
      agreement with other studies our results suggest that early diagnosis and
      treatment by immediate anticoagulation are important in preventing the serious
      consequences of portal and mesenteric vein occlusion. The role of more invasive
      approaches is less well defined. Since in 18 patients (90%) of the non-cirrhotic
      cases in the present series causative factors were found which may have
      therapeutic implications, aetiological screening seems worthwhile in every case
      with PVT.

PMID- 16106328
TI  - Cytologically malignant lymphoid pericardial effusion with benign clinical
      outcome.
AB  - BACKGROUND: Isolated malignant pericardial effusion is a manifestation of primary
      cardiac lymphoma (PCL) and primary effusion lymphoma (PEL), rare types of non
      Hodgkin's lymphoma (NHL). The diagnosis is based on different cytological methods
      and analyses including DNA-image cytometry (ICM-DNA). DNA-aneuploidy has been
      reported to be highly specific for malignancy. CASE DESCRIPTIONS AND RESULTS: A
      75-year-old man and a 66-year-old woman underwent urgent pericardiocentesis for
      cardiac tamponade due to large pericardial effusion. In both patients pericardial
      fluid analysis showed highly atypical blastic lymphoid cells expressing CD45
      (both patients) and CD20 (assessed only in one patient), and ICM-DNA revealed
      significant DNA-aneuploidy (2c deviation index 9.22 and 10.73 respectively, 75%
      and 60% respectively of the target nuclei in aneuploid areas). Extensive staging
      examinations did not identify any other tumour manifestation. Although in neither
      of the two patients systemic chemotherapy was administered, both were free of
      cancer after a follow-up of ten and nine years respectively. CONCLUSIONS: Despite
      the highly atypical cytomorphology including unequivocal DNA aneuploidy, long
      term survival in both patients strongly suggests that pronounced reactive
      lymphocytic changes are probably due to viral pericarditis rather than PCL or PEL
      as underlying conditions. It seems that DNA-aneuploidy may be not absolutely
      specific for the detection of malignant lymphoid cells in pericardial fluid.

PMID- 16106330
TI  - Nurse staffing levels and quality of care in Northeastern Pennsylvania nursing
      homes.
AB  - This study evaluated current nurse staffing levels in 90 licensed nursing homes
      in Northeastern Pennsylvania to determine whether they are significantly
      different from state and national averages. It further examined the association
      between nurse staffing and quality of patient care provided to nursing home
      residents. Findings indicate that although nurse staffing levels appear to be
      comparable with state and national averages, quality of care might be negatively
      affected when nurse staffing levels are reduced. Practical recommendations for
      solutions to the current nurse recruitment and retention crises are presented to
      ensure adequate nurse staffing and quality of care to elderly citizens.

PMID- 16106331
TI  - The role of education in managing fatigue, anxiety, and sleep disorders in women
      undergoing chemotherapy for breast cancer.
AB  - This study examined the effect of informational audiotapes on patients' self-care
      behaviors (SCBs) to manage chemotherapy side effects of fatigue, anxiety, and
      sleep disturbance. Seventy-one women with breast cancer participated. Thirty
      three received audiotapes on SCBs to manage side effects. Three telephone
      interviews were conducted. Overall, women who received education demonstrated
      more SCBs, a wider range of SCBs, increased use of SCBs over time, and less
      anxiety. Nursing time for education in busy clinics is minimal. Patient anxiety
      in the clinic environment interferes with learning. Audiotapes are an effective
      tool for use at home, providing for teaching and reinforcement of patient
      education.

PMID- 16106332
TI  - The quality of pressure ulcer prediction and prevention in home health care.
AB  - The purpose of this study was to assess the quality of pressure ulcer prediction
      and prevention in home health care. Randomly selected Medicare-certified home
      care agencies in four midwestern states were surveyed. The overall response rate
      was 44% (n = 128). Approximately half (57.8%) of the responding agencies assessed
      all patients for pressure ulcer risk upon admission; another 4.7% assessed only
      chair or bed-bound patients. Clinical nursing judgment was the most commonly
      (72%) used method for assessing risk; only 21% of the agencies used a validated
      tool such as the Braden Scale or the Norton Scale to identify those at risk.
      Approximately one third of the reporting agencies had prediction and/or
      prevention policies. Only 18.0% of home health care agencies identified
      recommended interventions in a pressure ulcer prevention protocol. Findings
      suggest opportunities for improvement in pressure ulcer prediction and prevention
      practice in home health care.

PMID- 16106333
TI  - Acquiring medical services for individuals with mental retardation in community
      based housing facilities.
AB  - As a result of deinstitutionalization, individuals with mental retardation (MR)
      were moved into the community and primary care practices. Residential agency
      directors now routinely determine health care decisions. Understanding of issues
      involved in acquiring services and the clinical decision-making experiences of 13
      service agency directors representing 1,400 individuals with MR were
      investigated. This descriptive study with a qualitative exploratory design
      included structured interviews that were content analyzed. Four themes describe
      the barriers encountered, which resulted in the delay or denial of appropriate
      health services. These themes include effects of stigma, knowledge limitations,
      resource deficits, and inconsistent decision making. Knowledge of these
      experiences will assist nurses in problem solving and advocating for the holistic
      competent care of individuals with MR.

PMID- 16106334
TI  - The effect of cognitive-behavioral group therapy on the self-esteem, depression,
      and self-efficacy of runaway adolescents in a shelter in South Korea.
AB  - This study examined the effects of cognitive-behavioral group therapy (CBT) on
      the self-esteem, depression, and self-efficacy of runaway adolescents residing in
      a shelter in Seoul, South Korea. The study used a control group pretest-posttest
      design. The experimental group and the control group consisted of 14 and 13 male
      subjects, respectively, with subjects having been randomly assigned to these
      groups. The experimental group participated in a CBT that consisted of eight
      sessions over an 8-week period; the control group did not participate in the
      program. To examine the effects of the CBT on dependent variables, the Wilcoxon
      signed rank test was used. The scores on depression decreased significantly (z = 
      2.325, p = .02) and those on self-efficacy increased significantly (z = -2.098, p
      = .03) after the intervention in the experimental group. There was no significant
      change on self-esteem (z = -1.19, p = .23). In the control group, the scores on
      depression, self-esteem, and self-efficacy did not change significantly after the
      intervention period. The CBT developed in this study consisted of structured and
      specific content that could be usefully applied to runaway adolescents residing
      in a shelter.

PMID- 16106335
TI  - Recruitment and retention in a longitudinal palliative care study.
AB  - A longitudinal feasibility study regarding quality of life and interventions for
      patients with advanced cancer or AIDS and their family caregivers was conducted
      to determine issues related to their recruitment and retention and to obtain
      pilot data relevant to the development of a larger study. At the completion of
      the study, a focus group consisting of the members of the palliative care
      research team was convened to identify barriers to and facilitators of the
      research process based on their research experience. The purpose of this article
      is to (1) describe recruitment, mortality rates, attrition rates, and compliance
      with data collection of patients and family caregivers experiencing an advanced
      illness and to (2) examine the researchers' perspectives regarding barriers to
      and facilitators of the research process that relate to patients and family
      caregivers, institutions, the data collection process, and their personal
      experiences. Implications for palliative care research are discussed.

PMID- 16106336
TI  - A randomized controlled trial of an individualized motivational intervention on
      smoking cessation for parents of sick children: a pilot study.
AB  - This is a pilot study of a randomized controlled trial of an individualized
      motivational intervention (IMI) provided by nurses to help smoking parents of
      sick children quit smoking. Eighty parents who brought their sick children to the
      hospital were entered into the study. The intervention group received an IMI from
      a trained nurse counselor and telephone reminders were given 1 week after the
      intervention. The quit rate at 1 month was 7.5% (95% CI, 0-21) in the
      intervention group and 2.5% (95% CI, 0-7) in the control group. Preliminary
      results indicated that the IMI provided by nurses seemed to be effective in
      helping resistant parents of sick children stop smoking. They also suggested that
      it was acceptable and feasible to implement such intervention in a pediatric
      outpatient clinic/ward in Hong Kong.

PMID- 16106337
TI  - A comparison study: paper-based versus web-based data collection and management.
AB  - The purpose of this pilot study was to compare the cost, accuracy, and efficiency
      of a web-enhanced handheld computer data collection system with those of the
      traditional paper-based data collection and management system and to increase
      awareness/knowledge of researchers on these two data collection and management
      methods. This is an important topic because funding resources are diminishing and
      high startup costs associated with automated data collection systems may give
      researchers pause when faced with these financial expenditures. Hence, this
      information will position grant writers and funders to make intelligent decisions
      regarding the feasibility and advantage of web-enhanced electronic data
      collection strategies.

PMID- 16106338
TI  - Return-on-investment models.

PMID- 16106339
TI  - Current literature in mass spectrometry.

PMID- 16106340
TI  - Biological tissue imaging with time-of-flight secondary ion mass spectrometry and
      cluster ion sources.
AB  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) using liquid metal ion
      guns (LMIGs) is now sensitive enough to produce molecular-ion images directly
      from biological tissue samples. Primary cluster ions strike a spot on the sample
      to produce a mass spectrum. An image of this sample is achieved by rastering the
      irradiated point over the sample surface. The use of secondary ion mass
      spectrometry for mapping biological tissue surfaces provides unique analytical
      capabilities; in particular, it enables in a single acquisition a large variety
      of biological compounds to be localised on a micrometer scale and scrutinised for
      colocalisations. Without any treatment of the sample, this method is fully
      compatible with subsequent and complementary analyses like fluorescence
      microscopy, histochemical staining, or even matrix-assisted laser
      desorption/ionisation imaging. Basic physical concepts, required instrumentation
      (ion source and mass analyzer), sample preparation methods, image acquisition,
      image processing, and emerging biological applications will be described and
      discussed.

PMID- 16106341
TI  - Enhancement of matrix-assisted laser desorption/ionization photodissociation
      tandem time-of-flight mass spectra; spectral reduction and cleanup of
      isotopomeric contamination.
AB  - Weak signal intensity and poor precursor ion selection are the major difficulties
      in tandem time-of-flight (TOF) mass spectrometry of ions generated by matrix
      assisted laser desorption/ionization (MALDI). Even though the latter can be
      overcome in photodissociation (PD) tandem TOF mass spectrometry via ion pulse-PD
      laser pulse synchronization, clean monoisotopic selection of precursor ions of
      high m/z can often be difficult for various reasons. A considerable enhancement
      of post-source decay (PSD) and PD tandem mass spectra has been achieved in this
      work via single-ion detection and post-acquisition reduction of the spectra.
      Also, an algorithm has been developed to clean up isotopomeric contamination when
      the resolution for precursor ion selection is less than adequate. A high-quality
      tandem TOF mass spectrum which results from PD of virtually monoisotopic
      precursor ions has been obtained.

PMID- 16106342
TI  - Nitrogen balance and delta15N: why you're not what you eat during nutritional
      stress.
AB  - While past experiments on animals, birds, fish, and insects have shown changes in
      stable isotope ratios due to nutritional stress, there has been little research
      on this topic in humans. To address this issue, a small pilot study was
      conducted. Hair samples from eight pregnant women who experienced nutritional
      stress associated with the nausea and vomiting of morning sickness (hyperemesis
      gravidarum) were measured for carbon (delta13C) and nitrogen (delta15N) stable
      isotope ratios. The delta13C results showed no change during morning sickness or
      pregnancy when compared with pre-pregnancy values. In contrast, the delta15N
      values generally increased during periods of weight loss and/or restricted weight
      gain associated with morning sickness. With weight gain and recovery from
      nutritional stress, the hair delta15N values displayed a decreasing trend over
      the course of gestation towards birth. This study illustrates how delta15N values
      are not only affected by diet, but also by the nitrogen balance of an individual.
      Potential applications of this research include the development of diagnostic
      techniques for tracking eating disorders, disease states, and nitrogen balance in
      archaeological, medical, and forensic cases.

PMID- 16106343
TI  - Determination of agrochemical compounds in soya plants by imaging matrix-assisted
      laser desorption/ionisation mass spectrometry.
AB  - Detection and imaging of the herbicide mesotrione (2-(4-mesyl-2
      nitrobenzoyl)cyclohexane-1,3-dione) and the fungicide azoxystrobin (methyl (E)-2
      {2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate), on the
      surface of the soya leaf, and the detection and imaging of azoxystrobin inside
      the stem of the soya plant, have been achieved using matrix-assisted laser
      desorption/ionisation quadrupole time-of-flight mass spectrometry. In leaf
      analysis experiments, the two pesticides were deposited onto the surface of
      individual soya leaves on growing plants. The soya leaves were removed and
      prepared for direct and indirect (following blotting onto matrix-coated cellulose
      membranes) imaging analysis at different periods after initial pesticide
      application. In stem analysis experiments, azoxystrobin was added to the nutrient
      solution of a soya plant growing in a hydroponics system. The plant was left for
      48 h, and then horizontal and vertical stem sections were prepared for direct
      imaging analysis. The images obtained demonstrate the applicability of MALDI
      imaging to the detection and imaging of small organic compounds in plant tissue
      and further extend the analytical repertoire of the versatile MALDI technique.

PMID- 16106344
TI  - Assembly of the hexameric Escherichia coli arginine repressor investigated by
      nano-electrospray ionization time-of-flight mass spectrometry.
AB  - The arginine repressor (ArgR) from Escherichia coli regulates genes for L
      arginine metabolism and is a required recombination factor for colE1 plasmid
      replication. Both functions require binding of L-arginine to the protein. In this
      work, nano-electrospray ionization time-of-flight mass spectrometry (nano-ESI
      TOFMS) is used to study conformational and oligomeric states of intact ArgR and
      its isolated structural domains. In agreement with X-ray diffraction studies, it
      is shown that ArgR oligomerizes to form hexamers in both the presence and absence
      of L-arginine, and the basic unit of oligomerization appears to be the trimer.
      Higher-order assembly into dodecamers is also detected. The isolated C-terminal
      domain is found to associate into trimers and hexamers whereas the N-terminal
      domain is detected in its monomeric form. The observed species distributions
      suggest a role for the N-terminal domain in hexamer stabilization.

PMID- 16106345
TI  - Use of monoatomic and polyatomic projectiles for the characterisation of
      polylactic acid by static secondary ion mass spectrometry.
AB  - The application of polyatomic primary ions is a strongly developing branch of
      static secondary ion mass spectrometry (S-SIMS), since these projectiles allow a
      significant increase in the secondary ion yields to be achieved. However, the
      different limitations and possibilities of certain polyatomic primary ions for
      use on specific functional classes of samples are still not completely known.
      This paper compares the use of monoatomic and polyatomic primary ions in S-SIMS
      for thin layers of polylactic acid (PLA), obtained by spin-coating solutions on
      silicon wafers. Bombardment with Ga+, Xe+ and SF5+ primary ions allowed the
      contribution of the projectile mass and number of atoms in the gain in ion yield
      and molecular specificity (relative importance of high m/z and low m/z signals)
      to be assessed. Samples obtained by spin-coating solutions with increasing
      concentration showed that optimal layer thickness depended on the primary ion
      used. In comparison with the use of Ga+ projectiles, the yield of structural ions
      increased by a factor of about 1.5 to 2 and by about 7 to 12 when Xe+ and SF5+
      primary ion bombardment were applied, respectively. A detailed fragmentation
      pattern was elaborated to interpret ion signal intensity changes for different
      projectiles in terms of energy deposition and collective processes in the
      subsurface, and the internal energy of radical and even-electron precursor ions.

PMID- 16106347
TI  - Identification of heat-induced degradation products from purified betanin,
      phyllocactin and hylocerenin by high-performance liquid
      chromatography/electrospray ionization mass spectrometry.
AB  - Betanin, phyllocactin (malonylbetanin) and hylocerenin (3-hydroxy-3
      methylglutarylbetanin) were isolated from purple pitaya (Hylocereus polyrhizus
      [Weber] Britton and Rose) juice, and their degradation products generated by
      heating at 85 degrees C were subsequently monitored by high-performance liquid
      chromatography/electrospray ionization tandem mass spectrometry. Thermal
      degradation of phyllocactin and hylocerenin in purified solution excluding the
      alleged protective effects by the juice matrix is reported for the first time.
      Betanin was predominantly degraded by hydrolytic cleavage, while decarboxylation
      and dehydrogenation were of minor relevance. In contrast, hylocerenin showed a
      strong tendency to decarboxylation and dehydrogenation, hydrolytic cleavage of
      the aldimine bond occurring secondarily. Phyllocactin degradation was most
      complex because of additional decarboxylation of the malonic acid moiety as well
      as generation and subsequent degradation of betanin due to phyllocactin
      demalonylation. Upon prolonged heating, all betacyanins under observation formed
      degradation products characterized by an additional double bond at C2-C3.
      Hydrolytic cleavage of the aldimine bond of phyllocactin and hylocerenin yielded
      previously unknown acylated cyclo-dopa derivatives traceable by positive
      ionization, while application of ESI(-) facilitated the detection of a
      glycosylated aminopropanal derivative and dopamine, which have never been
      described before as betanin degradation products.

PMID- 16106348
TI  - 'All-in-one' analysis for metabolite identification using liquid
      chromatography/hybrid quadrupole time-of-flight mass spectrometry with collision
      energy switching.
AB  - The removal of bottlenecks in discovery stage metabolite identification studies
      is an ongoing challenge for the pharmaceutical industry. We describe the use of
      an 'All-in-One' approach to metabolite characterization that leverages the fast
      scanning and high mass accuracy of hybrid quadrupole time-of-flight mass
      spectrometry (QqToFMS) instruments. Full-scan MS and MS/MS data is acquired using
      collision energy switching without the preselection, either manually or in a data
      dependent manner, of precursor ions. The acquisition of 'clean' MS/MS data is
      assisted by the use of ultrahigh-performance chromatography. Data acquired using
      this method can then be mined post-acquisition in a number of ways. These include
      using narrow window extracted ion chromatograms (nwXICs) for expected
      biotransformations, XICs for the product ions of the parent compound and/or
      expected modification of these product ions, and neutral loss chromatograms. This
      approach has the potential to be truly comprehensive for the determination of in
      vitro biotransformations in a drug discovery environment.

PMID- 16106349
TI  - Assessment of acute and chronic pain symptoms in children with cystic fibrosis.
AB  - Pain is important to assess and treat in children with cystic fibrosis (CF),
      because pain symptoms may limit children's ability to participate in their CF
      related care and may reduce their overall well-being and quality of life. The
      aims of this study were to: 1) assess acute and chronic pain symptoms as reported
      by children with CF, and 2) examine the relationship between pain symptoms and
      disease severity as measured by percentage of forced expired volume in 1 sec
      (FEV1%). Forty-six children completed a self-report questionnaire assessing
      characteristics of chronic disease-related pain (frequency, intensity, duration,
      associated emotional upset, and location of pain). Children also rated their pain
      intensity associated with common CF-related procedures. The primary locations of
      pain reported were the abdominal/pelvic region, chest, and head/neck. Forty-six
      percent of the sample described pain occurring at least once per week. Most
      children reported their pain intensity as mild and of short duration. However, a
      small subgroup of children reported longer-lasting and moderately intense pain.
      Children with chest pain were found to be particularly at risk for experiencing
      more functional limitations and a significantly lower FEV1% compared to children
      without chest pain. The majority of children reported that nonpharmacological
      therapies (e.g., medication, rest, or distracting activities) provided some pain
      relief. Disease-related pain is common for children and adolescents with CF,
      suggesting that pain assessment should be a routine part of their clinical care.
      Further research is clearly needed to better understand the sources of pain and
      how best to provide relief.

PMID- 16106350
TI  - A structural study of model peptides derived from HIV-1 integrase central domain.
AB  - The HIV-1 integrase (IN) catalyzes the integration of viral DNA in the human
      genome. In vitro the enzyme displays an equilibrium of monomers, dimers,
      tetramers and larger oligomers. However, its functional oligomeric form in vivo
      is not known. We report a study of the auto-associative properties of three
      peptides denoted K156, E156 and E159. These derive from the alpha4 helix of the
      IN catalytic core. The alpha4 helix is an amphipatic helix exposed at the surface
      of the protein and could be involved in the oligomerization process through its
      hydrophobic face. The peptides were obtained from the replacement of several
      amino acid residues by more helicogenic ones in the alpha4 helix peptide. K156
      carries the basic residues Lys156 and Lys159, which have been shown important for
      the binding of IN to viral DNA. In E156 and E159 they are replaced with the
      acidic residue Glu. A fourth peptide K(E)156 obtained from the replacement of
      hydrophobic residues with Glu in K156 in order to abolish the auto-associative
      properties is used as a negative control. The capacity shown by peptides for
      alpha-helical formation is demonstrated by circular dichroism (CD) analysis
      performed in aqueous solution and in aqueous trifluoroethanol (TFE) mixtures.
      Both electrospray ionization mass spectrometry (ESI-MS) and glutaraldehyde
      chemical cross-linking show that peptides adopt different solvent-dependent
      equilibriums of monomers, dimers, trimers and tetramers. Oligomerization of
      peptides in aqueous solution is related to their ability to form helical
      structures. Addition of a small amount of TFE (<10%) stimulates helix
      stabilization and the interhelical hydrophobic contacts. Higher amounts of TFE
      alter the hydrophobic contacts and disrupt the oligomeric species. In addition to
      hydrophobic interactions, the patterns indicate that the biologically important
      Lys156 and Lys159 residues also participate in helix association. K(E)156 despite
      its ability to adopt a helical structure is unable to associate into oligomers,
      demonstrating the importance of hydrophobic contacts for oligomerization. Thus,
      the designed peptides provide us information on the functional properties of the
      alpha4 IN that seems to hold a dual role in DNA recognition and protein
      oligomerization.

PMID- 16106351
TI  - Electronic substituent effects in the electron impact mass spectrometry of 2
      (arylazo)-4-phenylphenols.
AB  - A mass spectrometric study of a set of six novel 2-(arylazo)-4-phenylphenols 1-6
      was performed. The electron impact spectra were acquired and analyzed for five of
      the compounds in order to establish a fragmentation pattern. The suggested
      pathways were investigated and confirmed by means of tandem mass spectrometry
      (MS/MS) experiments together with high-resolution accurate mass data. However,
      the sixth molecule, a sodium sulfonate salt, was studied using fast atom
      bombardment (FAB) ionization in positive and negative modes. In addition, some
      electronic substituent effects were investigated by analyzing Hammett-McLafferty
      linear free energy correlations for some peaks derived from the corresponding
      molecular ions. Also, the role of the O-H...N hydrogen bond present in the target
      compounds was analyzed. The roles of these H-bonds were consistent with the
      corresponding acidity constant values obtained experimentally as well as by
      theoretical quantum chemistry calculations using HF/6-31 + G(d,p) and B3LYP/6
      31G(d,p). Some spectrometric data were correlated with topological properties
      derived from the atoms-in-molecules (AIM) theory.

PMID- 16106352
TI  - Tandem mass spectrometric analysis of cyclophosphamide, ifosfamide and their
      metabolites.
AB  - A detailed multi-stage (MSn) fragmentation study of cyclophosphamide (CP),
      ifosfamide (IF) and their major metabolites, using an ion-trap mass spectrometer
      and a Q-TOF mass spectrometer, was performed with the aid of specifically
      deuterium-labeled analogs. The analytes showed good responses in positive-ion
      electrospray mass spectrometry as [MH]+ ions. Tandem mass spectra revealed a
      wealth of structurally specific ions, allowing characterization of the
      fragmentation pathways of these analytes. The major fragmentation pathways of the
      protonated CP and IF are elimination of ethylene from C5 and C6 of 1,3,2
      oxazaphosphorine-2-oxide via a McLafferty rearrangement, and cleavage of the P-N
      bond. However, their activated 4-OOH and 4-OH metabolites primarily underwent
      hydrogen peroxide elimination and dehydration, respectively, followed by
      fragmentation pathways similar to those of CP and IF. These results should prove
      useful in structural elucidation of future analogs of CP and IF, and/or of their
      metabolites.

PMID- 16106353
TI  - Characterization of adducts formed between human serum albumin and the butadiene
      metabolite epoxybutanediol.
AB  - 1,3-Butadiene (BD) has been classified as a potential human carcinogen. It occurs
      in the environment as well as in industrial settings. In humans, BD is readily
      metabolized to reactive epoxides (e.g. 1,2-epoxy-3,4-butanediol). In this study,
      conjugates between human serum albumin (HSA) and EBD were synthesized (molar
      ratios of 1:600, 1:1 and 1:0.1; HSA/EBD) under physiological conditions. The
      1:600 conjugate and a blank HSA sample were digested with trypsin to obtain
      specific peptides that were fractionated by preparative liquid chromatography
      (LC). The fractions were analyzed using nanoelectrospray quadrupole time-of
      flight mass spectrometry (nanoES-QqTOFMS). Adducted HSA tryptic peptides were
      identified and the adducted amino acid residues were identified by sequence
      analysis based on tandem mass spectrometry (MS/MS). A total of 26 2,3,4
      trihydroxybutyl (THB) adducts were identified on 23 tryptic peptides in the
      HSA/EBD conjugate. The adducted amino acids were the N-terminal aspartic acid
      residue, six glutamic acid residues, five histidine residues and 14 lysine
      residues. Results from the nanoES-QqTOFMS experiments were used to set up a more
      sensitive liquid chromatographic/mass spectrometric (LC/MS) analysis using
      selected reaction monitoring. Eight of the adducted peptides could be detected in
      tryptic digests of the 1:0.1 HSA/EBD conjugate.

PMID- 16106354
TI  - Expression of the whey acidic protein (Wap) is necessary for adequate nourishment
      of the offspring but not functional differentiation of mammary epithelial cells.
AB  - Whey acidic protein (WAP) is the principal whey protein found in rodent milk,
      which contains a cysteine-rich motif identified in some protease inhibitors and
      proteins involved in tissue modeling. The expression of the Wap gene, which is
      principally restricted to the mammary gland, increases more than 1,000-fold
      around mid-pregnancy. To determine whether the expression of this major milk
      protein gene is a prerequisite for functional differentiation of mammary
      epithelial cells, we generated conventional knockout mice lacking two alleles of
      the Wap gene. Wap-deficient females gave birth to normal litter sizes and,
      initially, produced enough milk to sustain the offspring. The histological
      analysis of postpartum mammary glands from knockout dams does not reveal striking
      phenotypic abnormalities. This suggests that the expression of the Wap gene is
      not required for alveolar specification and functional differentiation. In
      addition, we found that Wap is dispensable as a protease inhibitor to maintain
      the stability of secretory proteins in the milk. Nevertheless, a significant
      number of litters thrived poorly on Wap-deficient dams, in particular during the
      second half of lactation. This observation suggests that Wap may be essential for
      the adequate nourishment of the growing young, which triple in size within the
      first 10 days of lactation. Important implications of these findings for the use
      of Wap as a marker for advanced differentiation of mammary epithelial cells and
      the biology of pluripotent progenitors are discussed in the final section.

PMID- 16106355
TI  - Transgenic expression of Cre recombinase in mitral/tufted cells of the olfactory
      bulb.
AB  - Olfactory information is conveyed from the periphery to the olfactory cortices
      through mitral and tufted (M/T) cells in the olfactory bulb. A mouse with a
      specific expression of Cre recombinase in M/T cells is essential for genetic
      marking of M/T cells and manipulating their properties. Protocadherin 21 (Pcdh21)
      expression is highly restricted to M/T cells. Here we report a transgenic mouse
      line, Pcdh21-Cre, in which 10-kb mouse Pcdh21 promoter drives the expression of
      Cre recombinase. In Pcdh21-Cre mice, Cre recombinase activity is predominantly
      detected in M/T cells, visualized with the anti-CFP immunostaining in offspring
      of a cross between Pcdh21-Cre and the reporter Rosa26-loxP-stop-loxP-CFP strain.
      These results demonstrate that the 10-kb Pcdh21 promoter can drive transcription
      in M/T cells and Pcdh21-Cre mice can be used to excise floxed DNA fragments in
      M/T cells, which provides a valuable tool to reveal the structure and function of
      the central olfactory circuits.

PMID- 16106356
TI  - Leukotriene synthesis during respiratory syncytial virus bronchiolitis: influence
      of age and atopy.
AB  - Respiratory syncytial virus (RSV) infection is the most common cause of
      bronchiolitis in infants and an important risk factor for the development of
      recurrent wheezing and asthma. Cysteinyl leukotrienes were implicated in the
      pathophysiology of these diseases, and are being targeted for their diagnosis and
      therapy. We measured urinary leukotriene E4 (LTE4) in infants with RSV
      bronchiolitis in comparison with controls without respiratory infection, and
      investigated whether medical and family history, age, and passive exposure to
      tobacco smoke are related to urinary leukotriene excretion. We studied 33 infants
      with bronchiolitis and 25 controls, 1-12 months of age. Demographic and
      historical data were obtained from informed-consent forms and questionnaires
      completed by the parents. RSV was detected in nasal secretions by enzyme-linked
      immunoassay. Urine samples were collected on day of admission and were analyzed
      for LTE4 with an enzyme-linked immunoassay. Urinary LTE4 was 8-fold higher in
      infants with bronchiolitis than in controls. Leukotriene excretion was
      significantly higher in infected infants <6 months of age with a medical history
      of eczema or dry cough and/or family history of asthma. Multivariate analysis
      revealed that eczema and dry cough are independently associated with high LTE4
      excretion during bronchiolitis. Exposure to tobacco smoke did not affect urinary
      LTE4. Our study shows that leukotriene synthesis during bronchiolitis is
      particularly elevated in younger infants with an atopic/asthmatic background.
      Urinary LTE4 may become a valuable, noninvasive marker for the identification of
      patients who will benefit most from therapy with leukotriene modifiers for
      management of bronchiolitis.

PMID- 16106357
TI  - Clinical validation of high-resolution fast spin-echo MR colonography after colon
      distention with air.
AB  - To evaluate the feasibility of MR colonography (MRC) with air using two
      dimensional (2D) T1-weighted fast spin-echo (T1wFSE) in patients scheduled for
      conventional colonoscopy (CC) after classic bowel preparation, and assess the
      ability of the technique to detect colonic lesions. The distention was sufficient
      for diagnosis, and the technique provided adequate delineation of the wall in the
      majority of segments. Residual fluid obscured the wall in different segments,
      especially in the ascending and descending colon (supine position) and in the
      cecum, transverse, and sigmoid colon (prone position). These findings were
      consistent with CT colonography. MRC visualized three lesions, missed one lesion
      >10 mm, visualized none of four lesions <5 mm, and yielded one false-positive
      lesion (5-10 mm). Missed lesions can be due to inconsistency in the slice
      positions between consecutive breath-holds, which is inherent to the multishot
      technique. Residual fluid may have obscured the smaller lesions. The shortcomings
      of the technique are limited coverage and signal drop-off at the borders of the
      field of view (FOV). Before multishot 2D T1wFSE colonography can become a valid
      screening method, improved patient preparation and a more practical technique are
      needed.

PMID- 16106358
TI  - Glomerular filtration rate measured using the Patlak plot technique and contrast
      enhanced dynamic MRI with different amounts of gadolinium-DTPA.
AB  - We determined the optimum gadolinium (Gd)-DTPA dose and time window for
      calculating the glomerular filtration rate (GFR) using contrast-enhanced (CE)
      dynamic MRI and the Patlak plot technique. Twelve adult volunteers with healthy
      kidneys were included in the study. As a reference method the GFR was measured by
      iopromide plasma clearance. A three-dimensional gradient-echo (GRE) sequence with
      a flip angle of 50 degrees was used for MRI. Signal was measured using a body
      surface coil with four elements. Each volunteer was examined on four days using 2
      mL, 4 mL, 8 mL, or 16 mL of Gd-DTPA 0.5 mmol/mL dissolved with sodium chloride
      (NaCl) 0.9% to a total of 60 mL. The injection rate was 1 mL/second. A Patlak
      plot was calculated from the kidney and aorta signals. The mean reference GFR was
      133 mL/min (min-max, 116-153 mL/min). The best correlation of GFR calculated from
      MRI data compared to the reference method was found in a time window 30-90
      seconds after aortic signal rise using 16 mL Gd-DTPA. Pearson's correlation
      coefficient was r = 0.83, and the standard deviation (SD) from the line of
      regression was 10.5 mL/minute. We found a significantly lower average GFR(MR)
      using 16 mL Gd-DTPA compared to 4 mL and 2 mL in the late time window 60-120
      seconds post aortic rise. A dose of 16 mL Gd-DTPA was optimal for measuring GFR
      using dynamic MRI and the Patlak plot technique. The slope should be measured in
      a time window of 30-90 seconds post aortic rise.

PMID- 16106359
TI  - A liquid chromatography/tandem mass spectrometry method for the simultaneous
      quantification of isoniazid and ethambutol in human plasma.
AB  - Isoniazid and ethambutol are commonly used in various combination treatments for
      tuberculosis, and for this reason a rapid and sensitive liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and
      validated for simultaneous quantification of these two drugs in human plasma.
      After a simple protein precipitation using methanol, the analytes and the
      internal standard metformin were chromatographed on a C18 column and detected by
      MS/MS. An atmospheric pressure chemical ionization interface was chosen to reduce
      ion suppression from sample matrix components and provide high sensitivity. The
      LC retention times for isoniazid and ethambutol were 2.46 and 2.27 min,
      respectively. The method was linear in the concentration range of 10.0-5000 ng/mL
      for each analyte using 100 microL plasma. The intra- and inter-day precisions,
      expressed as the relative standard deviation (RSD), were less than 5.7 and 6.4%,
      determined from QC samples for isoniazid and ethambutol, and the accuracies were
      within +/-2.1% and +/-4.5% in terms of relative error, respectively. The method
      was successfully employed in a pharmacokinetic study after oral administration of
      a multicomponent formulation containing 150 mg isoniazid, 500 mg ethambutol, 150
      mg rifampicin and 250 mg pyrazinamide.

PMID- 16106360
TI  - The Drosophila ACP65A cuticle gene: deletion scanning analysis of cis-regulatory
      sequences and regulation by DHR38.
AB  - The regulatory sequences of the Drosophila ACP65A cuticle gene were analyzed in
      vivo in transgenic flies, using both fusion genes constructs and transposase
      mediated deletions within a P element containing ACP65A regulatory sequences
      fused to the lacZ gene (deletion scanning). The sequences located between -594
      and +161 are sufficient to confer both temporal and spatial expression
      specificities, indicating the presence of tissue-specific enhancers and response
      elements to hormone-induced factors. In addition, timing of expression and tissue
      specificity appear to be controlled by distinct cis-regulatory elements, which
      suggests the existence of independent hormonal and tissue-specific signaling
      pathways. Gain and loss of function studies also implicate DHR38, the Drosophila
      homolog of the vertebrate NGFI-B-type nuclear receptors, as an important
      activator of the ACP65A gene.

PMID- 16106361
TI  - Generation and characterization of the PKC gamma-Cre mouse line.
AB  - PKCgamma is a protein kinase C (PKC) isoform that is expressed in the central
      nervous system (CNS). We generated a PKCgamma-Cre mouse line and characterized
      the expression and activity of the Cre protein. Our studies show that Cre
      expression largely recapitulates the endogenous expression of PKCgamma. Several
      major sites of Cre expression are the cerebral cortex, hippocampus, thalamus,
      amygdala, and spinal cord. Examination of PKCgamma-Cre/ROSA26 mice reveals a
      similar X-gal staining pattern in the CNS, indicating that Cre recombinase is
      capable of removing LoxP sites in vivo. These data indicate that the PKCgamma-Cre
      mouse line could be a useful reagent for generating Cre-mediated tissue-specific
      knockouts in the CNS.

PMID- 16106362
TI  - Generation of progeny from embryonic stem cells by microinsemination of male germ
      cells from chimeric mice.
AB  - Mice chimeric for embryonic stem (ES) cells have not always successfully produced
      ES-derived offspring. Here we show that the male gametes from ES cells could be
      selected in male chimeric mice testes by labeling donor ES cells or host
      blastocytes with GFP. Male GFP-expressing ES-derived germ cells occurred as
      colonies in the chimeric testes, where the seminiferous tubules were separated
      into green and non-green regions. When mature spermatozoa from green tubules were
      used for microinsemination, GFP-expressing offspring were efficiently obtained.
      Using a reverse study, we also obtained ES-derived progeny from GFP-negative ES
      cells in GFP-labeled host chimeras. Furthermore, we showed this approach could be
      accelerated by using round spermatids from the testes of 20-day-old chimeric
      mice. Thus, this technique allowed us to generate the ES cell-derived progeny
      even from the low contributed chimeric mice, which cannot produce ES-origin
      offspring by natural mating.

PMID- 16106363
TI  - Generation of conditional Mef2cloxP/loxP mice for temporal- and tissue-specific
      analyses.
AB  - Mef2c belongs to the myocyte enhancer factor 2 (MEF2) family of MADS-box
      containing transcription factors, which have been shown to be important for
      various processes involved in cell differentiation, cell survival, and apoptosis.
      Previous gene-targeting studies have demonstrated a role for mef2c in early heart
      development since mice lacking mef2c die at embryonic day 9.5 due to cardiac and
      vascular defects. Since the early embryonic lethality of mef2c prevents an
      examination of its role in the later stages of heart development, conditional
      mef2c(loxP/loxP) mice were generated to allow for temporal- and tissue-specific
      analyses. We report here that general Cre recombinase-mediated removal of the
      second coding exon of mef2c phenocopied the original mef2c null. Additionally,
      myocardial-specific removal of mef2c resulted in viable offspring, demonstrating
      that while mef2c is required for the early development of the heart, it is not
      necessary for the formation of the heart after looping morphogenesis.

PMID- 16106364
TI  - Combined T1-T2 mapping of human femoro-tibial cartilage with turbo-mixed imaging
      at 1.5T.
AB  - PURPOSE: To evaluate the influence of Gd-DTPA on cartilage T2 mapping using turbo
      mixed (tMIX) imaging, and to show the possible usefulness of the tMIX technique
      for simultaneously acquiring T1 and T2 information in cartilage. MATERIALS AND
      METHODS: Twenty volunteers underwent MRI of the knee using the tMIX sequence
      before and after gadolinium administration. T1 and T2 maps were calculated. The
      mean T1 was determined on the pre- and postcontrast T1 maps. T2 relaxation values
      before and after gadolinium administration were statistically analyzed. RESULTS:
      The obtained relaxation values are in correspondence with previously published
      data. The mean T1 before gadolinium administration was 449 msec +/- 34.2 msec
      (SD), and after gadolinium administration it was 357 msec +/- 55.8 msec (SD). The
      postcontrast T1 relaxation range was 221.5-572.8 msec. The mean T2 of the
      precontrast T2 maps was 34.2 msec +/- 3.1 msec (SD), and the mean T2 of the
      postcontrast T2 maps was 32.5 msec +/- 3.1 msec (SD). These are statistically
      significant different values. A correction for the postcontrast T2 values, using
      a back-calculation algorithm, yielded a 98% correlation with the precontrast T2
      values. CONCLUSION: The absolute difference of pre- and postcontrast T2 is very
      small and is ruled out using the back-calculation algorithm. Combined T1-T2 tMIX
      cartilage mapping is a valuable alternative for separate T1 and T2 cartilage
      mapping.

PMID- 16106365
TI  - Comparison of Gd [DTPA-bis (2-aminoethoxy) ethane] polymeric contrast agent with
      gadodiamide injection for interstitial MR lymphography: experimental study with
      rabbits.
AB  - PURPOSE: To compare the differences between macromolecular and small molecular
      contrast agents in interstitial magnetic resonance (MR) lymphography. MATERIALS
      AND METHODS: In two groups of rabbits (N = 12 each), 0.5-mL volumes of 0.5 M and
      0.1 M gadodiamide, respectively, were injected subcutaneously into the dorsal
      feet of both hind legs. After a 24-hour interval, 0.5 mL of Gd [DTPA-bis (2
      aminoethoxy) ethane] polymeric contrast agent (Gd-poly-DTPA-EOEA) injection (0.1
      M) was injected into the same sites in each rabbit. T1-weighted three-dimensional
      gradient-echo and maximum intensity projection (MIP) images were obtained before
      and after the administration of each agent. The nodal maximum short-axis diameter
      (MSAD) and signal-to-noise ratio (SNR) at each time point were measured.
      Postmortem measurements of nodal MSADs were also performed. The nodal MSAD
      measurements obtained by MR lymphography were compared with the postmortem
      measurements. As an additional control experiment, six rabbits received a
      subcutaneous injection of 0.5 mL of 0.1 M gadodiamide at the same sites as those
      described above. This procedure was repeated after a 24-hour interval to
      determine whether the first injected gadodiamide had any effect on the
      performance of the subsequently injected agent, by comparing the differences in
      nodal MSADs obtained by MR lymphography after each injection. RESULTS: Gd-poly
      DTPA-EOEA showed a significantly longer enhancement plateau compared to
      gadodiamide. In comparison with postmortem measurements, nodal measurements by MR
      lymphography with Gd-poly-DTPA-EOEA at the peak-enhancement phase revealed no
      significantly different MSADs (P > 0.05), whereas nodal measurements by MR
      lymphography with gadodiamide showed significantly smaller MSADs (P < 0.05). A
      comparison of the nodal MSADs measured in two gadodiamide-enhanced MR
      examinations after the 24-hour interval showed no significant difference (P >
      0.05). CONCLUSION: Interstitial MR lymphography with polymeric Gd-poly-DTPA-EOEA
      enhancer enables more sufficient and reliable visualization of lymph nodes
      compared to small molecular gadodiamide.

PMID- 16106366
TI  - Initial experience with balanced turbo field echo in depicting carotid artery
      stenosis: comparison with multiple overlapping thin slab acquisition and 3D
      contrast-enhanced magnetic resonance angiography.
AB  - PURPOSE: To compare balanced turbo field echo (bTFE) with multiple overlapping
      thin slice acquisition (MOTSA) and contrast-enhanced MR angiography (CE-MRA) in
      depicting carotid artery stenosis. MATERIALS AND METHODS: In this study 86
      patients with cerebrovascular disease, who had been referred for a carotid
      examination, were imaged. All of the patients underwent MOTSA and one of four
      bTFE sequences followed by CE-MRA. Formatted maximum intensity projections (MIPs)
      and source images were read in a blinded fashion by a radiologist. Inter- and
      intrasequence statistical analyses were performed. RESULTS: We first compared
      image quality (IQ) and fat, background, and venous suppression using four
      distinct bTFE protocols in 118 carotid arteries, and found that bTFE4 performed
      the best. We then compared IQ, grades of stenosis, and background and venous
      suppression among bTFE4, MOTSA, and CE-MRA. bTFE produced significantly better IQ
      and venous suppression (P < 0.001), and higher SNR and CNR (P < 0.05) when
      compared to MOTSA. CONCLUSION: The bTFE sequence is robust and provides high
      quality images in patients with mild to moderate carotid artery stenosis. Even
      though there is a tendency to overestimate stenosis with bTFE compared to CE-MRA,
      the shorter scan time of bTFE coupled with enhanced SNR and CNR measurements
      validates it as a clinically useful adjunct to MOTSA, if not a replacement.

PMID- 16106367
TI  - Cellular disorders induced by high magnetic fields.
AB  - PURPOSE: To evaluate whether static high magnetic fields (HMFs), in the range of
      10-17 T, affect the cytoskeleton and cell organization in different types of
      mammalian cells, including fibroblasts, epithelial cells, and differentiating
      neurons. MATERIALS AND METHODS: Cells were exposed to HMF for 30 or 60 minutes
      and subsequently assessed for viability. Cytoskeleton arrays and focal adhesions
      were visualized using immunofluorescence microscopy. RESULTS: Cell exposure to
      HMF over 10 T in the case of cycling cells, and over 15 T in the case of neurons,
      affected cell viability, apparently because of cell detachment from culture
      dishes. In the remaining adherent cells, the organization of actin assemblies was
      perturbed, and both cell adhesion and spreading were impaired. Moreover, in the
      case of neurons, exposure to HMF induced growth cone retraction and delayed cell
      differentiation. CONCLUSION: Cell exposure to HMF (over 10T and 15 T in the case
      of cycling cells and neurons, respectively) affects the cell cytoskeleton, with
      deleterious effects on cell viability, organization, and differentiation. Further
      studies are needed to determine whether such perturbations, as observed here in
      cultured cells, have consequences in whole animals.

PMID- 16106368
TI  - Interleukin-10 inhibits lipopolysaccharide-induced survival and extracellular
      signal-regulated kinase activation in human neutrophils.
AB  - Lipopolysaccharide (LPS) induces a marked delay in human neutrophil apoptosis
      that is reversed by the anti-inflammatory cytokine IL-10. The effect of IL-10 is
      specific since other agents that delay neutrophil apoptosis are not affected. To
      investigate mechanisms underlying the actions of IL-10, we examined signaling
      pathways activated by LPS per se and in response to IL-10. The MAPK kinase (MEK)
      1 inhibitor PD098059, the protein kinase C (PKC) inhibitor Ro31,8220, and the
      phosphatidylinositol-3 kinase (PI3-K) inhibitor LY294002 all partially reversed
      LPS-mediated retardation of neutrophil apoptosis, but the p38 MAPK inhibitor
      SB203850 did not. LPS activates the transcription factor NF-kappaB, however, IL
      10 did not affect the ability of LPS to activate NF-kappaB as assessed by IkappaB
      alpha proteolysis. Although IL-10 did not alter activation of ERK by GM-CSF or
      TNF-alpha, it did inhibit activation induced by LPS. Thus our data illustrate
      that LPS-induced neutrophil survival is regulated by the MAPK, PKC and PI3-K
      pathways as well as NF-kappaB, and can be reversed by IL-10, through a mechanism
      involving inhibition of ERK activation. Because of the specific nature of this
      inhibition, we conclude that IL-10 interferes with an ERK activation pathway,
      which is not involved in GM-CSF or TNF-alpha signaling.

PMID- 16106369
TI  - Characterization of antibodies that inhibit HIV gp120 antigen processing and
      presentation.
AB  - Antibodies to the CD4-binding site (CD4bs) of HIV-1 envelope gp120 have been
      shown to inhibit MHC class II presentation of this antigen, but the mechanism is
      not fully understood. To define the key determinants contributing to the
      inhibitory activity of these antibodies, a panel of anti-CD4bs monoclonal
      antibodies with different affinities was studied and compared to antibodies
      specific for the chemokine receptor-binding site or other gp120 regions. Anti
      CD4bs antibodies that completely obstruct gp120 presentation exhibit three common
      properties: relatively high affinity for gp120, acid-stable interaction with
      gp120, and the capacity to slow the kinetics of gp120 proteolytic processing.
      None of these antibodies prevents gp120 internalization into APC. Notably, the
      broadly virus-neutralizing anti-CD4bs IgG1b12 does not block gp120 presentation
      as strongly, because although IgG1b12 has a relatively high affinity, it
      dissociates from gp120 more readily at acidic pH and only moderately retards
      gp120 proteolysis. Other anti-gp120 antibodies, regardless of their affinities,
      do not affect gp120 presentation. Hence, high-affinity anti-CD4bs antibodies that
      do not dissociate from gp120 at endolysosomal pH obstruct gp120 processing and
      prevent MHC class II presentation of this antigen. The presence of such
      antibodies could contribute to the dearth of anti-gp120 T helper responses in
      chronically HIV-1-infected patients.

PMID- 16106370
TI  - Differential expression of human granzymes A, B, and K in natural killer cells
      and during CD8+ T cell differentiation in peripheral blood.
AB  - NK cells and cytotoxic T lymphocytes can induce apoptosis in virus-infected and
      transformed target cells via the granule exocytosis pathway. The key components
      of the cytolytic granules are perforin and several serine esterases, termed
      granzymes. While the cellular distribution of human granzymes A (GrA) and B (GrB)
      has been well characterized much less is known about the expression pattern of
      human granzyme K (GrK). In this study GrA, GrB, and GrK expression was analyzed
      in human peripheral blood lymphocytes using flow cytometry. There was a distinct
      population of GrK expressing CD8+ T cells with a CD27+/CD28+/CCR5high/CCR7
      /perforin-/low/IFN-gamma+ memory-like phenotype, while all CD56bright NK cells
      were also positive for GrK. In addition, GrK was also expressed in subpopulations
      of CD56+ T cells, CD4+ T cells, and TCRgammadelta+ T cells. In contrast, GrB was
      primarily expressed in CD56dim NK cells and differentiated memory CD8+ T cells
      with the CD27-/low/CD28-/low/CCR5-/low/CCR7-/CD11b+/perforinhigh phenotype. Only
      few CD8+ T cells expressed both GrB and GrK. GrA was found to be co-expressed in
      all GrB- and GrK-expressing T cells. Our findings suggest that granzyme
      expression during the differentiation process of memory CD8+ T cells might be as
      follows: GrA+/GrB-/GrK+ --> GrA+/GrB+/GrK+ --> GrA+/GrB+/GrK-.

PMID- 16106371
TI  - Soluble, dimeric HLA DR4-peptide chimeras: an approach for detection and
      immunoregulation of human type-1 diabetes.
AB  - Still there are no effective methods to predict or cure type 1 diabetes (T1D) in
      humans. Soluble, dimeric MHC class II-peptide (DEF) chimeras have potential for
      both early diagnosis and immunospecific therapy. DEF chimeras prevent and reverse
      diabetes in mice by stimulating antigen-specific type 1 T regulatory cell (Tr1)
      like cells. We also showed that diabetes could be predicted by changes in the
      phenotype of autoreactive CD4 T cells in peripheral blood. Herein, we
      demonstrated that human DEF (HLA-DR*0401/Fcgamma1) chimeras expressing peptides
      of beta-cell antigens stimulate Tr1-like cells in blood of patients with T1D, non
      diabetic relatives, and controls. Furthermore, the specific and stable binding of
      DEF chimeras to cognate TCR and CD4 coreceptor allowed quantification and
      phenotyping of autoreactive CD4 T cells in non-stimulated blood by FACS. Our
      results indicate that (1) autoreactive CD4 T cells to GAD65 autoantigen are
      commonly present in humans expressing diabetes-susceptible HLA-DR*0401 molecules;
      (2) these autoreactive T cells undergo avidity maturation upon encountering the
      self antigen early in life; (3) the disease is associated with an imbalance
      between autoreactive CD4+CD25+ and CD4+CD69+ T cells specific for GAD65. Based on
      this, we propose a model to explain the kinetics of autoreactive CD4 T cells in
      blood during the natural history of T1D.

PMID- 16106372
TI  - Expansion of CD4 T cells expressing a highly restricted TCR structure specific
      for a single parasite epitope correlates with high pathology in murine
      schistosomiasis.
AB  - The hepatic immunopathology in schistosomiasis mansoni is mediated by CD4 T cells
      specific for egg antigens and varies considerably among mouse strains. Previous
      studies in high pathology C3H mice suggested that a strong T cell response was
      due to the recognition of an immunodominant epitope within the major egg antigen
      Sm-p40 (Sm-p40(234-246)). Using a panel of T cell hybridomas, we have now
      examined the egg antigen-specific TCR repertoire in two high pathology strains,
      C3H and CBA. We found that nearly half of the hybridomas responded to the Sm
      p40(234-246 )epitope and, of these, nearly all expressed Valpha11.3 associated
      with Vbeta8. Furthermore, in response to egg antigen stimulation, transcript
      levels of Valpha11.3J36 (the most prevalent rearrangement expressed by Sm-p40(234
      246)-specific hybridomas), increased in high pathology (CBA) but not in low
      pathology BALB/c strains. Our findings suggest that exacerbated schistosome egg
      induced immunopathology can be driven by T cells expressing a highly restricted
      TCR structure specific for a single parasite epitope.

PMID- 16106373
TI  - Understanding what makes a good versus a bad vaccine.
AB  - The majority of the HIV vaccines under development are aimed at stimulating T
      cell responses. Therefore, it is critical to delineate the factors regulating the
      generation of the T cell responses and to develop strategies maximizing vaccine
      induced T cell responses. The identification of these factors and the delineation
      of the kinetics of the generation of vaccine-induced immune responses have been
      hard to investigate, due to the limited number of precursor naive antigen
      specific T cells. To overcome these obstacles, Estcourt and collaborators have
      developed an elegant strategy that consists of an in vivo mouse model employing
      transfer of naive CFSE-labeled TCR-transgenic T lymphocytes into syngeneic
      nontransgenic recipients prior to vaccination. Using this model, the authors
      demonstrate that the dose, the route of administration and the type of vaccine
      determine the magnitude, the dissemination and the kinetics of vaccine-induced T
      cell responses. Furthermore, the mouse model of Estcourt and collaborators may
      represent the basis for the development of powerful in vivo experimental
      strategies to evaluate vaccine candidates.

PMID- 16106374
TI  - Evaluation of normal fatty replacement of the thymus with chemical-shift MR
      imaging for identification of the normal thymus.
AB  - PURPOSE: To clarify the influences of age and gender on normal fatty replacement
      of the thymus in childhood, adolescence, and early adulthood using chemical-shift
      MRI. MATERIALS AND METHODS: A total of 95 normal subjects (52 males and 43
      females, mean age = 15.6 years, range = 7-25 years) who underwent chemical-shift
      MRI of the thymus were assessed prospectively. Signal intensity loss (SIL) of the
      thymus was determined by dividing the thymus/muscle ratio on the opposed-phase
      image by that on the in-phase image. We evaluated SIL for its correlation with
      age and gender, and assessed SIL of the thymus with uncommon morphological
      features. RESULTS: A significant correlation was found between SIL and age (r =
      0.750, P < 0.001). There was no significant difference in SIL between the
      genders. No significant SIL was identified in any of the subjects aged 10 years
      or less. However, significant SIL was found in 70.8% of those aged 11-20 years,
      100% of those aged 21 years or more, and 46.2% of subjects with uncommon
      morphological features of the thymus. CONCLUSION: Chemical-shift MRI can depict
      physiologic fatty infiltration within the normal thymus in subjects over 11 years
      of age. It is crucial to correlate these normal age-related findings with
      clinical cases in order to avoid misinterpretation.

PMID- 16106375
TI  - Examining the collision-induced decomposition spectra of ammoniated triglycerides
      as a function of fatty acid chain length and degree of unsaturation. I. The
      OXO/YOY series.
AB  - A series of positionally pure triglycerides (TAGs) of the form OXO and YOY, where
      O is the oleate moiety and X and Y are large arrays of different fatty acid
      moieties, was synthesized and analyzed by reversed-phase high-performance liquid
      chromatography/tandem mass spectrometry. The intensities of the collision-induced
      decomposition (CID) products of ammoniated TAGs (ammonium ion adducts) were
      examined as a function of chain length, degree of unsaturation, double-bond
      position, and cis/trans configuration of X and Y. The major CID products, the
      diglyceride fragment ions and the MH+ ion, were plotted as functions of chain
      length for the saturated and mono-unsaturated series of X and Y. Different trends
      for each of these series were observed. Trends in the abundances of these
      fragment ions were also characterized as a function of degree of unsaturation in
      the TAGs. In general, the fractional abundances of the MH+ ions vary linearly
      with degree of unsaturation. However, the presence of double bonds positioned
      close to the carbonyl carbon of the fatty acid chain promotes the formation of
      the diglyceride fragment ion corresponding to loss of that fatty acid. Mechanisms
      of the formation and decomposition of ammoniated TAGs are proposed that fit the
      trends observed in the data. Extensions of this work are described, and a vision
      of a derived library of CID spectra is discussed as a platform for comprehensive
      analysis of complex TAG mixtures.

PMID- 16106376
TI  - Electrospray tandem mass spectrometry of new porphyrin amino acid conjugates.
AB  - Porphyrin amino acid conjugates with one or two porphyrin units were analyzed by
      electrospray ionization tandem mass spectrometry (ESI-MS/MS). The ESI-MS spectra
      of all the porphyrins studied, obtained in positive ion mode, show the presence
      of the corresponding protonated molecule [M+H]+; ESI-MS spectra of diporphyrinyl
      compounds also show the doubly charged ions [M+2H]2+. The fragmentations of these
      ions induced by collision with argon were studied (ESI-MS/MS). ESI-MS/MS gives
      detailed structural information about the amino acids associated with the
      porphyrin. Cleavage of the bonds in the vicinity of the porphyrin moiety and
      those involving the side chain of amino acid residues gives structural
      information about this type of association. A fragmentation common to all
      derivatives corresponds to the cleavage of the phenyl-CO bond. The expected
      cleavage of the amide bond, that links the porphyrin to the amino acid moiety, is
      a minor fragmentation, which in some cases is even absent. The MS/MS spectra of
      the monoporphyrinyl derivatives show product ions characteristic of the amino
      acid linked to the porphyrin; the fragmentation also indicates when the amino
      acids has a terminal carboxylic group or a terminal ester group. The
      fragmentations of the diporphyrinyl compounds occur mainly by the cleavage of the
      spacer, leading, in the case of the doubly charged ions, to predominantly mono
      charged ions, indicating a preferential location of the two protons in separated
      porphyrinic units.

PMID- 16106377
TI  - Real value prediction of solvent accessibility in proteins using multiple
      sequence alignment and secondary structure.
AB  - The present study is an attempt to develop a neural network-based method for
      predicting the real value of solvent accessibility from the sequence using
      evolutionary information in the form of multiple sequence alignment. In this
      method, two feed-forward networks with a single hidden layer have been trained
      with standard back-propagation as a learning algorithm. The Pearson's correlation
      coefficient increases from 0.53 to 0.63, and mean absolute error decreases from
      18.2 to 16% when multiple-sequence alignment obtained from PSI-BLAST is used as
      input instead of a single sequence. The performance of the method further
      improves from a correlation coefficient of 0.63 to 0.67 when secondary structure
      information predicted by PSIPRED is incorporated in the prediction. The final
      network yields a mean absolute error value of 15.2% between the experimental and
      predicted values, when tested on two different nonhomologous and nonredundant
      datasets of varying sizes. The method consists of two steps: (1) in the first
      step, a sequence-to-structure network is trained with the multiple alignment
      profiles in the form of PSI-BLAST-generated position-specific scoring matrices,
      and (2) in the second step, the output obtained from the first network and
      PSIPRED-predicted secondary structure information is used as an input to the
      second structure-to-structure network. Based on the present study, a server
      SARpred (http://www.imtech.res.in/raghava/sarpred/) has been developed that
      predicts the real value of solvent accessibility of residues for a given protein
      sequence. We have also evaluated the performance of SARpred on 47 proteins used
      in CASP6 and achieved a correlation coefficient of 0.68 and a MAE of 15.9%
      between predicted and observed values.

PMID- 16106378
TI  - Proton transfer in a Thr200His mutant of human carbonic anhydrase II.
AB  - Human carbonic anhydrase II (HCA II) has a histidine at position 64 (His64) that
      donates a proton to the zinc-bound hydroxide in catalysis of the dehydration of
      bicarbonate. To examine the effect of the histidine location on proton shuttling,
      His64 was replaced with Ala and Thr200 replaced with histidine (H64A-T200H
      HCAII), effectively relocating the proton shuttle residue 2 A closer to the zinc
      bound hydroxide compared to wild type HCA II. The crystal structure of H64A-T200H
      HCA II at 1.8 A resolution shows the side chain of His200 directly hydrogen
      bonded with the zinc-bound solvent. Different proton transfer processes were
      observed at pH 6 and at pH 8 during the catalytic hydration-dehydration cycle,
      measured by mass spectrometry as the depletion of 18O from C18O2 by H64A-T200H
      HCA II. The process at pH 6.0 is attributed to proton transfer between the side
      chain of His200 and the zinc-bound hydroxide, in analogy with proton transfer
      involving His64 in wild-type HCA II. At pH 8.0 it is attributed to proton
      transfer between bicarbonate and the zinc-bound hydroxide, as supported by the
      dependence of the rate of proton transfer on bicarbonate concentration and on
      solvent hydrogen isotope effects. This study establishes that a histidine
      directly hydrogen-bonded to the zinc-bound hydroxide, can adopt the correct
      distance geometry to support proton transfer

PMID- 16106379
TI  - General and targeted statistical potentials for protein-ligand interactions.
AB  - We present a novel atom-atom potential derived from a database of protein-ligand
      complexes. First, we clarify the similarities and differences between two
      statistical potentials described in the literature, PMF and Drugscore. We
      highlight shortcomings caused by an important factor unaccounted for in their
      reference states, and describe a new potential, which we name the Astex
      Statistical Potential (ASP). ASP's reference state considers the difference in
      exposure of protein atom types towards ligand binding sites. We show that this
      new potential predicts binding affinities with an accuracy similar to that of
      Goldscore and Chemscore. We investigate the influence of the choice of reference
      state by constructing two additional statistical potentials that differ from ASP
      only in this respect. The reference states in these two potentials are defined
      along the lines of Drugscore and PMF. In docking experiments, the potential using
      the new reference state proposed for ASP gives better success rates than when
      these literature reference states were used; a success rate similar to the
      established scoring functions Goldscore and Chemscore is achieved with ASP. This
      is the case both for a large, general validation set of protein-ligand structures
      and for small test sets of actives against four pharmaceutically relevant
      targets. Virtual screening experiments for these targets show less discrimination
      between the different reference states in terms of enrichment. In addition, we
      describe how statistical potentials can be used in the construction of targeted
      scoring functions. Examples are given for cdk2, using four different targeted
      scoring functions, biased towards increasingly large target-specific databases.
      Using these targeted scoring functions, docking success rates as well as
      enrichments are significantly better than for the general ASP scoring function.
      Results improve with the number of structures used in the construction of the
      target scoring functions, thus illustrating that these targeted ASP potentials
      can be continuously improved as new structural data become available.

PMID- 16106381
TI  - Radioprotection of Swiss albino mice by Emblica officinalis.
AB  - The fruit pulp of Emblica officinalis (EO) is an important drug used in Indian
      systems of medicine for several diseases and as a tonic. In view of its
      multifarious uses, the plant extract (aqueous) was tested for its radioprotective
      properties against sublethal gamma radiation (9 Gy) in Swiss albino mice. Animals
      were divided into two groups and irradiated with gamma radiation externally, with
      or without EO extract, which was given orally at different doses before
      irradiation. The dose of fruit pulp extract found to be most effective against
      radiation was 100 mg/kg b.wt. This dose increased the survival time and reduced
      the mortality rate of mice significantly. Furthermore, body weight loss in EO
      administered irradiated animals was significantly less in comparison with animals
      who were given radiation only.

PMID- 16106382
TI  - Protective effect of Toki-shakuyaku-san on amyloid beta25-35-induced neuronal
      damage in cultured rat cortical neurons.
AB  - Amyloid beta protein (Abeta) is the major component of senile plaques, the
      pathological hallmark of the neurodegeneration associated with Alzheimer's
      disease (AD). This study investigated the effect of Toki-shakuyaku-san (TSS), a
      traditional medicine, on Abeta25-35-induced neuronal death and lipid peroxidation
      assessed by measuring lactate dehydrogenase (LDH) and malondialdehyde (MDA),
      respectively. Abeta25-35 at 10 microM induced neuronal damage and increased the
      LDH and MDA. TSS at concentrations of 100 and 300 microg/mL significantly reduced
      the Abeta25-35-induced neuronal death and the lipid peroxidation. These results
      suggest that TSS has a protective effect against Abeta25-35-induced neuronal
      damage. TSS may be beneficial for the treatment of AD.

PMID- 16106383
TI  - Antipyretic and analgesic activities of Caesalpinia bonducella seed kernel
      extract.
AB  - Ethanolic extract (70%) of Caesalpinia bonducella seed kernel has been subjected
      for its antipyretic and antinociceptive activities in adult albino rats or mice
      of either sex at 30, 100 and 300 mg/kg orally. The extract demonstrated marked
      antipyretic activity against Brewer's yeast-induced pyrexia in rats. The extract
      had significant central analgesic activity in hot plate and tail flick methods.
      It also exhibited marked peripheral analgesic effect in both acetic acid-induced
      writhing test in mice and Randall-Selitto assay in rats. It also significantly
      inhibited the formalin-induced hind paw licking in mice. In conclusion, the
      present study suggests that the ethanolic extract of Caesalpinia bonducella seed
      kernel possesses potent antipyretic and antinociceptive activities and thus,
      validates its use in the treatment of pain and pyretic disorders.

PMID- 16106384
TI  - Radiation protection of DNA and membrane in vitro by extract of Hemidesmus
      indicus.
AB  - Radioprotective effect of H. indicus root extract on lipid peroxidation in rat
      liver microsomes and plasmid DNA was examined. Hemidesmus indicus (HI) root
      extract was found to protect microsomal membranes as evident from reduction in
      lipid peroxidation values. The extract could also protect DNA from radiation
      induced strand breaks.

PMID- 16106385
TI  - Oregano and clove essential oils induce surface alteration of Saccharomyces
      cerevisiae.
AB  - The antimicrobial properties of volatile aromatic oils have been recognized since
      antiquity. Oregano and clove oils have been shown to possess a broad spectrum of
      antimicrobial activity. In this paper, the fungicidal action of these two
      essential oils was studied on the yeast model Saccharomyces cerevisiae. Yeast
      cell lysis was shown by the release of substances absorbing at 260 nm. In
      addition, scanning electron microscopy analyses revealed that the surface of
      treated cells by oregano and clove oils was significantly damaged.

PMID- 16106386
TI  - Cytotoxicity of some Russian ethnomedicinal plants and plant compounds.
AB  - The cytotoxic action of crude ethanol extracts from 61 plant species used in
      Russian ethnomedicine for alleviating symptoms of diseases in cancer patients was
      studied on cultured human lymphoblastoid Raji cells. Extracts from Chelidonium
      majus, Potentilla erecta, Chamaenerium angustfolium, Filipendula ulmaria and
      Inula helenium possessed marked cytotoxicity, suppressing the growth of the cells
      at concentrations of 10 and 50 microg/mL. The cytotoxicity of purified active
      compounds from selected plant species was evaluated along with pharmaceutical
      antineoplastic drugs methotrexate, fluorouracil, cyclophosphamide and
      vinblastine. Sesquiterpene lactones helenin, telekin and artemisinin, aromatic
      polyacetylene capillin, and alkaloid preparation sanguirythrine suppressed cell
      growth at concentrations of 1-2 microg/mL, which exceeds the cytotoxicity of
      cyclophosphamide and fluorouracil.

PMID- 16106387
TI  - The effect of annatto on insulin binding properties in the dog.
AB  - Various plants are used in Caribbean folklore for the treatment of a variety of
      illnesses including diabetes mellitus. Preliminary investigations of several
      crude plant extracts have indicated that the annatto (Bixa orellana), among
      others, does in fact exhibit hypoglycaemic properties. This present investigation
      sought to isolate the hypoglycaemic principle(s) from the crude extract and to
      determine the mechanism of action. Purification experiments employing thin layer
      chromatography (TLC) and high performance liquid chromatography (HPLC) resulted
      in an oil-soluble, partially purified annatto extract. The latter caused a
      decrease in blood glucose level of 5.62+/-0.13 (n=34) mmol/dL versus 6.31+/-0.12
      (n=34) for the control (p<0.01) 1 h after administration. This hypoglycaemia
      persisted for an additional hour when the oral glucose tolerance test (OGTT) was
      performed on dogs treated with annatto and compared with the control. Plasma
      insulin levels measured at 1.0 h showed that there was an increase in plasma
      insulin levels of 59.57+/-8.3 microIU/mL for the annatto treated dogs versus
      40.95+/-5.46 microIU/mL for the control (p<0.05), this elevation persisted
      throughout the duration of the OGTT which followed. Insulin receptor studies,
      using a modification of the method of Gambhir et al. done on mononuclear
      leucocytes and erythrocytes obtained from blood taken 1 h after administration
      showed that there was an increase in the percentage receptor binding when
      compared with the control. Insulin affinity results showed that there was an
      increase of 1.8+/-0.2x10(8) m-1 (n=12) in mononuclear leucocytes for the annatto
      treated dogs versus 1.2+/-0.2x10(8) m-1 for the control (p<0.05). In the
      enythrocytes, there was also an increase in affinity from 1.2+/-0.2x10(8) m-1 to
      2.3+/-0.2x10(8) m-1 for the control and treated animals, respectively. In
      conclusion, it can be stated that annatto is responsible for the hypoglycaemic
      episodes seen in the dogs which was mediated by an increase in plasma insulin
      concentration as well as an increase in insulin binding on the insulin receptor
      due to elevated affinity of the ligand for the receptor.

PMID- 16106388
TI  - Cardamom extract as inhibitor of human platelet aggregation.
AB  - The inhibitory activity of cardamom extract was studied on human platelets.
      Platelet aggregation and lipid peroxidation were evaluated with platelet rich
      plasma (PRP) and platelet membranes, respectively, obtained from blood of healthy
      volunteers. Human platelets were subjected to stimulation with a variety of
      agonists including ADP (2.5 mM), epinephrine (2.5 mM), collagen (10 mM), calcium
      ionophore A 23187 (6 microM) and ristocetin (1.25 microg/mL). The IC50 were 0.49,
      0.21, 0.55 and 0.59 mg with ADP, epinephrine, collagen and calcium ionophore A
      23187, respectively, and no inhibition with ristocetin. The inhibitory effect was
      dose dependent with concentrations varying between 0.14 and 0.70 mg and time
      dependent at IC50. Lipid peroxidation induced by iron--ascorbic acid system in
      platelet membranes was analysed with malondialdehyde (MDA) as an index. An
      increase in concentration of cardamom has decreased the MDA formation
      significantly. Hence, it may be said that aqueous extract of cardamom may have
      component(s), which protect platelets from aggregation and lipid peroxidation.

PMID- 16106389
TI  - Antifungal activity of tuberose absolute and some of its constituents.
AB  - The antifungal activity of the absolute of tuberose (Polianthes tuberosa ) and
      some of its constituents were evaluated against the mycelial growth of
      Colletotrichum gloeosporioides on potato-dextrose-agar medium. Tuberose absolute
      showed only mild activity at a concentration of 500 mg/L. However, three
      constituents present in the absolute, namely geraniol, indole and methyl
      anthranilate exhibited significant activity showing total inhibition of the
      mycelial growth at this concentration.

PMID- 16106390
TI  - Evaluation of antipyretic activity of Calotropis gigantea (Asclepiadaceae) in
      experimental animals.
AB  - The roots of Calotropis gigantea have been used in leprosy, eczema, syphilis,
      elephantiasis, ulceration and cough in the Indian system of traditional medicine.
      The present communication evaluated its antipyretic activity by using yeast
      induced and TAB (Typhoid) vaccine-induced pyrexia in rats and rabbits. In both
      yeast-induced and TAB vaccine-induced fever, the fever was significantly reduced
      and the body temperature was normalized by administration of 200 and 400 mg/kg
      dose intraperitoneally. Based on the results of the present study it can be
      concluded that the extract of C. gigantea has potential antipyretic activity
      against both yeast-induced and TAB vaccine-induced fever, indicating the
      possibility of developing C. gigantea as a cheaper and potent antipyretic agent.

PMID- 16106391
TI  - Phytochemical, pharmacological and toxicological aspects of Hibiscus sabdariffa
      L.: a review.
AB  - This article reviews the reported phytochemical, pharmacological and
      toxicological properties of Hibiscus sabdariffa L. (English: roselle, red sorrel;
      Arabic: karkade), the calyces of which are used in many parts of the world to
      make cold and hot drinks. Nutritionally, these contain ascorbic acid (vitamin C).
      In folk medicine, the calyx extracts are used for the treatment of several
      complaints, including high blood pressure, liver diseases and fever. The
      pharmacological actions of the calyx extracts include strong in vitro and in vivo
      antioxidant activity. In rats and rabbits, the extract showed
      antihypercholesterolaemic, antinociceptive and antipyretic, but not
      antiinflammatory activities. In rat and man a strong antihypertensive action has
      been demonstrated. The effects of the calyx extracts on smooth muscles in vitro
      are variable, but they mostly inhibit the tone of the isolated muscles. In
      healthy men, consumption of H. sabdariffa has resulted in significant decreases
      in the urinary concentrations of creatinine, uric acid, citrate, tartrate,
      calcium, sodium, potassium and phosphate, but not oxalate. Oil extracted from the
      plant's seeds has been shown to have an inhibitory effect on some bacteria and
      fungi in vitro. The plant extracts are characterized by a very low degree of
      toxicity. The LD50 of H. sabdariffa calyx extract in rats was found to be above
      5000 mg/kg. A single report has suggested that excessive doses for relatively
      long periods could have a deleterious effect on the testes of rats. In view of
      its reported nutritional and pharmacological properties and relative safety, H.
      sabdariffa and compounds isolated from it (for example, anthocyanins and Hibiscus
      protocatechuic acid) could be a source of therapeutically useful products.

PMID- 16106392
TI  - Effect of some medicinal plants on plasma antioxidant system and lipid levels in
      rats.
AB  - Several inflammatory diseases are thought to be related to oxidative injury and
      free oxygen radicals have been proposed as important causative agents of heart
      disease and aging. To investigate the effects of daily intake of medicinal plants
      on antioxidant enzymes, lipid peroxidation and lipid profiles in rat, 28 rats
      were randomly divided into four groups and administered with three plant extracts
      (0.2 g/kg body weight): Piper cubeba (fruit), Physalis angulata (flower), Rosa
      hybrida (flower) and with saline as a control. After 3 weeks, superoxide
      dismutase (SOD), catalase, thiobarbituric acid reactive substance (TBARS),
      triglyceride (TG) and cholesterol levels in plasma were measured. The SOD
      activity of the Piper cubeba group and the catalase activity of the Piper cubeba
      and Rosa hybrida groups were significantly increased compared with the control
      group, while the SOD and catalase activities of the Physalis angulata group were
      not significantly changed (p<0.05). TBARS, a marker of lipid peroxidation, was
      significantly lower in all experimental groups compeered with the control group.
      No significant changes occurred in the TG, total- and LDL-cholesterol of all
      groups, but the HDL-cholesterol of the Physalis angulata group was significantly
      increased. This study showed that the intake of medicinal plants in rats results
      in an increase in antioxidant enzyme activity and HDL-cholesterol, and a decrease
      in malondialdehyde, which may reduce the risk of inflammatory and heart disease.

PMID- 16106393
TI  - Chemistry and hepatoprotective activity of an active fraction from Barleria
      prionitis Linn. in experimental animals.
AB  - Iridoid enriched fraction IF from the ethanol-water extract of aerial parts
      (leaves and stems) of Barleria prionitis Linn. was evaluated for hepatoprotective
      activity in various acute and chronic animal test models of hepatotoxicity. It
      afforded significant hepatoprotection against carbon tetrachloride, galactosamine
      and paracetamol induced hepatotoxicity. Silymarin, was used as reference
      hepatoprotective. In the safety evaluation study the oral LD50 was found to be
      more than 3000 mg/kg, with no signs of abnormalities or any mortality observed
      for 15 days period under observation after single dose of drug administration
      whereas intraperitoneal LD50 was found to be 2530 mg/kg+/-87 mg/kg. SE (n=10) in
      mice. The studies revealed significant and concentration dependent
      hepatoprotective potential of 'IF' as it reversed the majority of the altered
      hepatic parameters in experimental liver damage in rodents.

PMID- 16106394
TI  - Effect of Dianex, a herbal formulation on experimentally induced diabetes
      mellitus.
AB  - Dianex, a polyherbal formulation consisting of the aqueous extracts of Gymnema
      sylvestre, Eugenia jambolana, Momordica charantia Azadirachta indica, Cassia
      auriculata, Aegle marmelose, Withania somnifera and Curcuma longa was screened
      for hypoglycemic activity in normal and streptozotocin induced diabetic mice.
      Dianex was administered in different doses of 100-500 mg/kg/day orally in acute
      (6 h) and long-term (6 weeks) studies. Blood glucose levels were checked 2-6 h
      after treatment in acute studies and every 2 weeks in long-term studies. Body
      weight was recorded on the first and final day of the treatment in the long-term
      studies with diabetic mice. After 6 weeks, high-density lipoprotein,
      triglycerides, total cholesterol, alanine transaminase (ALT), aspertate
      transaminase (AST), urea and creatinine were estimated in serum of the diabetic
      mice. Glycogen and total protein levels were estimated in the liver. Also, the
      liver and pancreas was subjected to histological examination. Oral glucose
      tolerance and in vitro free radical scavenging activity was also studied. Dianex
      produced significant (p<0.05) hypoglycemic activity at 250-500 mg/kg doses in
      both normal and diabetic mice in acute and long-term studies. The body weight of
      diabetic mice significantly (p<0.05) increased with all tested doses of Dianex.
      The elevated triglycerides, cholesterol, ALT, AST, urea and creatinine levels in
      diabetic mice were significantly (p<0.05) reduced at the doses of 250 and 500
      mg/kg. The liver glycogen and protein levels were both significantly (p<0.05)
      increased in diabetic mice at 250 and 500 mg/kg doses. Dianex increased the
      glucose tolerance significantly (p<0.05) in both normal and diabetic mice at all
      the doses tested. Histopathological examination showed that the formulation
      decreased streptozotocin induced injury to the tissues at all the doses tested.
      It produced significant (p<0.05) free radical scavenging activity against ABTS+,
      DPPH and hydroxyl free radicals at the concentrations ranging between 10-1000
      microg/ml.Thus, in the present study, Dianex produced significant hypoglycemic
      activity in both normal and diabetic animals. It also reversed other diabetic
      complications in diabetic mice at 250 and 500 mg/kg doses. In our earlier study,
      Dianex was well tolerated in laboratory animals at higher doses (upto 10 g/kg in
      mice, acute toxicity; up to 2.5 g/kg in rats, subacute toxicity studies for 30
      days) without exhibiting any toxic manifestation. Hence, Dianex may be useful in
      the treatment of diabetes mellitus.

PMID- 16106395
TI  - Therapeutic role of Cuminum cyminum on ethanol and thermally oxidized sunflower
      oil induced toxicity.
AB  - Ethanol is one of the most widely used and abused drugs, increasing lipid levels
      in humans and experimental animals. Heating of oil rich in polyunsaturated fatty
      acids (PUFA) produces various lipid peroxidative end products that can aggravate
      the pathological changes produced by ethanol. In the present communication, the
      effect of Cuminum cyminum was investigated on alcohol and thermally oxidized oil
      induced hyperlipidaemia. The results showed increased activity of aspartate
      transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase
      (GGT) and increased levels of cholesterol, triglycerides and phospholipids in the
      plasma of rats given alcohol, thermally oxidized oil and alcohol+thermally
      oxidized oil when compared with the normal control group. The levels of tissue
      (liver and kidney) cholesterol and triglycerides were increased significantly in
      rats groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized
      oil when compared with the normal control rats. The levels were decreased when
      cumin was given along with alcohol and thermally oxidized oil. The level of
      phospholipids decreased significantly in the liver and kidney of groups given
      alcohol, thermally oxidized oil and alcohol+thermally oridized oil when compared
      with the normal control rats. The level increased when cumin was administered
      along with alcohol and thermally oxidized oil. The activity of phospholipase A
      and C increased significantly in the liver of groups given alcohol, thermally
      oxidized oil and alcohol+thermally oxidized oil when compared with the normal
      control rats, whereas the activity was decreased with the cumin treatment. The
      results obtained indicate that cumin can decrease the lipid levels in alcohol and
      thermally oxidized oil induced hepatotoxicity.

PMID- 16106396
TI  - Flavonoid of Drynaria fortunei protects against acute renal failure.
AB  - The flavonoid fraction (FF) from Drynaria fortunei was investigated to determine
      its biological activity expression in three acute renal failure animal models.
      Guinea pigs received 100 mg/kg of gentamicin (GM group), 100 mg/kg of GM plus 10
      mg/kg of FF (GMFF group), 10 mg/kg of FF (FF group) or saline (saline group)
      intramuscularly for 14 days. The blood urea nitrogen (BUN) and creatinine levels
      were found to be significantly higher in the GM group (22.70+/-3.84 mg/dL, 0.68+/
      0.05 mg/dL) than in the GMFF group (17.10+/-1.04 mg/dL, 0.58+/-0.09 mg/dL), the
      FF group (17.40+/-1.01 mg/dL, 0.49+/-0.20 mg/dL) and the saline group (17.50+/
      1.22 mg/dL, 0.50+/-0.02 mg/dL). Mice were treated once with 6 mg/kg of mercuric
      chloride, followed by 10 mg/kg of FF or saline. On days 3, 4 and 5, BUN and
      creatinine levels were found to be significantly higher in the HgCl2-saline group
      (74.00+/-39.20 mg/dL, 59.30+/-31.20 mg/dL, 74.00+/-37.30 mg/dL and 0.53+/-0.17
      mg/dL, 0.48+/-0.15 mg/dL 0.33+/-0.15 mg/dL) than in the HgCl2-FF group (19.50+/
      4.90 mg/dL, 43.00+/-26.30 mg/dL, 38.50+/-13.80 mg/dL and 0.23+/-0.05 mg/dL,
      0.30+/-0.12 mg/dL, 0.15+/-0.06 mg/dL).After surgery for 5/6-nephrectomy, ten mice
      received FF at a dose of 10 mg/kg/day and eight received saline for 42 days. The
      saline group survived for 12-62 days and the FF group survived for 20-320 days.
      The FF group had a significantly longer survival time than the saline group
      (p<0.05). Regeneration of kidney tubular cells and significantly enlarged
      convoluted tubules were noted in the pathology study of the FF group. In
      conclusion, the present study suggests that FF prevents nephrotoxicity, improves
      kidney function and promotes kidney primary epithelial tubular cell regeneration.

PMID- 16106397
TI  - Acute effects of guarana (Paullinia cupana Mart.) on mouse behaviour in forced
      swimming and open field tests.
AB  - Guarana, a herbal extract from the seeds of Paullinia cupana Mart. has been
      evaluated in comparison with caffeine on mouse behaviour in forced swimming and
      open field tests. Guarana (25 and 50 mg/kg, p.o.) and caffeine (10 and 20 mg/kg,
      p.o.) each significantly reduced the duration of immobility in the forced
      swimming test suggesting an antidepressant-like effect in mice. At these doses,
      neither substance affected ambulation in the open field test. However, a high
      dose of guarana (100 mg/kg) and caffeine (30 mg/kg) significantly enhanced the
      locomotor activity in the open field test. Caffeine, but not guarana, could
      effectively block an adenosine agonist, cyclopentyl adenosine (CPA)-induced
      increase in swimming immobility suggesting that mechanism(s) other than the
      adenosinergic mechanism are involved in the antidepressant-like activity of
      guarana.

PMID- 16106398
TI  - Curcumin (diferuloylmethane) inhibits constitutive active NF-kappaB, leading to
      suppression of cell growth of human T-cell leukemia virus type I-infected T-cell
      lines and primary adult T-cell leukemia cells.
AB  - Adult T-cell leukemia (ATL) is a fatal malignancy of T lymphocytes caused by
      infection with human T-cell leukemia virus type I (HTLV-I) and remains incurable.
      Curcumin (diferuloylmethane), the major pigment of the spice turmeric, can be
      potentially effective by promoting cell apoptosis. Here we examined whether
      curcumin is effective in the treatment of ATL. Curcumin prevented cell growth of
      HTLV-I-infected T-cell lines and primary ATL cells but not of normal peripheral
      blood mononuclear cells. Curcumin induced cell cycle arrest by reducing the
      expression of cyclin D1, Cdk1 and Cdc25C and apoptosis by reducing the expression
      of XIAP and survivin. Most of these genes are known to be regulated by NF-kappaB,
      which plays a critical role in oncogenesis by HTLV-I. Curcumin suppressed
      constitutive active NF-kappaB of HTLV-I-infected T-cell lines and primary ATL
      cells by inhibiting phosphorylation of IkappaBalpha. Curcumin also inhibited Tax
      induced NF-kappaB transcriptional activity. However, curcumin-induced suppression
      of cell growth did not correlate with Tax expression level. Curcumin inhibited
      the growth of HTLV-I-infected T-cell tumors implanted subcutaneously in SCID
      mice. Our results indicate that curcumin has tumor-suppressive activity against
      ATL.

PMID- 16106399
TI  - Macrophage migration and gene expression in response to tumor hypoxia.
AB  - Monocytes are recruited into tumors from the circulation along defined
      chemotactic gradients and they then differentiate into tumor-associated
      macrophages (TAMs). Recent evidence has shown that large numbers of TAMs are
      attracted to and retained in avascular and necrotic areas, where they are exposed
      to tumor hypoxia. At these sites, TAMs appear to undergo marked phenotypic
      changes with activation of hypoxia-inducible transcription factors, dramatically
      upregulating the expression of a large number of genes encoding mitogenic,
      proangiogenic and prometastatic cytokines and enzymes. As a consequence, high
      TAMs density has been correlated with increased tumor growth and angiogenesis in
      various tumor types. Since hypoxia is a hallmark feature of malignant tumors and
      hypoxic tumor cells are relatively resistant to radio- and chemotherapy, these
      areas have become a target for novel forms of anticancer therapy. These include
      hypoxia-targeted gene therapy in which macrophages are armed with therapeutic
      genes that are activated by hypoxia-responsive promoter elements. This restricts
      transgene expression to hypoxic areas, where the gene product is then released
      and acts on neighboring hypoxic tumor cells or proliferating blood vessels. In
      this way, the responses of macrophages to tumor hypoxia can be exploited to
      deliver potent antitumor agents to these poorly vascularized, and thus largely
      inaccessible, areas of tumors.

PMID- 16106400
TI  - Distribution of Epstein-Barr viral load in serum of individuals from
      nasopharyngeal carcinoma high-risk families in Taiwan.
AB  - The utility of EBV load as a tumor marker in nasopharyngeal carcinoma (NPC)
      patients suggests that it might also serve as a screening test for individuals
      who are at high risk for developing NPC. We previously demonstrated that
      unaffected individuals from high-risk families had elevated anti-EBV antibody
      levels compared to community controls. In this study, we measured EBV load using
      2 different real-time PCR assays (targeting BamH1W and polymerase gene sequences,
      respectively) carried out in 2 independent research labs in serum samples from 19
      untreated NPC cases, 11 healthy community controls and 100 unaffected individuals
      from families in which 2 or more individuals were affected with NPC. EBV genomes
      were detectable in 68% of NPC cases by the EBV BamH1W assay and in 74% by the EBV
      polymerase assay (kappa = 0.64). Patients with stage III or IV disease had
      significantly higher EBV load compared to those with stage I or II disease (p =
      0.008). EBV DNA was detected in a single community control sample by the EBV
      BamH1W assay and in none of the samples by the EBV polymerase assay. Only one of
      100 unaffected family members tested positive by both assays. An additional 14
      were positive by only one of the 2 EBV load assays used and usually in only one
      of the duplicate wells tested, all with very low viral loads (3-50 copies/ml). In
      addition, EBV load did not correlate with EBV serology results (anti-VCA, anti
      DNase, anti-EBNA-1) among these unaffected family members. In conclusion, our
      study suggests limited clinical utility of the EBV load test, in its current
      configuration, to screen individuals from high-risk families. Should a more
      sensitive or specific molecular assay be developed that is capable of detecting
      and distinguishing tumor-derived EBV genomes or gene products from true
      negatives, it could be evaluated as a possible screening tool for asymptomatic
      and early-stage NPC.

PMID- 16106401
TI  - Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal
      cancer cells.
AB  - The effect of conjugated linoleic acid (CLA) on peritoneal metastasis was
      examined by in vitro treatment of cancer cells and mouse peritoneal metastasis
      models. First, cell growth of MKN28 human gastric cancer cells and Colo320 human
      colon cancer cells was suppressed by CLA in a dose-dependent manner with an
      increment in apoptosis. CLA significantly inhibited invasion into type IV
      collagen-coated membrane of MKN28 and Colo320 cells (p < 0.05). CLA-induced
      growth inhibition was recovered by the exposure to antisense S
      oligodeoxynucleotide for peroxisome proliferator-activated receptor (PPAR)-gamma
      in both cell lines. BALB/c nu-nu mice were inoculated with MKN28 and Colo320
      cells into their peritoneal cavity, and administrated with CLA intraperitoneally
      (weekly, 4 times). CLA treatment did not affect food intake or weight gain of
      mice. CLA treatment significantly decreased metastatic foci of both cells in the
      peritoneal cavity (p < 0.005). Survival rate in mice inoculated with MKN28 or
      Colo320 cells was significantly recovered by CLA treatment (p = 0.0025 and
      0.0052, respectively). Protein production in MKN28 and Colo320 cells treated with
      CLA showed a decrease in epidermal growth factor receptor and transforming growth
      factor-alpha and an increase in Bax. These findings suggest that CLA inhibits
      metastasis of human gastric and colon cancer cells.

PMID- 16106402
TI  - Ursodeoxycholic acid inhibits interleukin 1 beta [corrected] and deoxycholic acid
      induced activation of NF-kappaB and AP-1 in human colon cancer cells.
AB  - Deoxycholic acid (DCA) has been implicated in colorectal carcinogenesis in humans
      with effects on proliferation and apoptosis, mediated at least in part by
      activation of transcription factors nuclear factor kappa B (NF-kappaB), activator
      protein 1 (AP-1) and protein kinase C (PKC) enzymes. Ursodeoxycholic acid (UDCA)
      is reported to reduce the frequency of colonic carcinogenesis in ulcerative
      colitis patients. Hence, we postulated that it might differ from DCA in its
      regulation of these transcription factors. The aim of the study was to determine
      effects of DCA and UDCA on NF-kappaB and AP-1 activation and explore its
      relationship to PKC. Human colonic tumour cell lines HCT116 were treated with
      DCA, UDCA, alone or pretreated with UDCA followed by DCA or IL-1beta. In other
      experiments, cells were pretreated with PKC inhibitors and then stimulated with
      DCA and IL-1beta or PMA. Gel shift assays were performed on nuclear extracts of
      the cells for NF-kappaB and AP-1 analysis. Western blot analyses and
      immunofluorescence were performed for Rel A (p65) and IkappaB-alpha levels on the
      treated cells. DCA increased NF-kappaB and AP-1 DNA binding. UDCA did not
      increase DNA binding of NF-kappaB and AP-1 and UDCA pretreatment inhibited DCA
      induced NF-kappaB and AP-1 DNA binding. PKC inhibitors blocked DCA-induced NF
      kappaB and AP-1 activation. These results were validated by Western blot analysis
      for RelA and IkappaB-alpha. In conclusion, UDCA did not induce NF-kappaB and AP-1
      DNA binding but also blocked DCA-induced NF-kappaB and AP-1 activation. These
      findings suggest a possible mechanistic role for UDCA in blocking pathways
      thought to be involved in colon carcinogenesis.

PMID- 16106403
TI  - Role of hepatocyte growth factor activator (HGF activator) in invasive growth of
      human glioblastoma cells in vivo.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional growth
      factor that is involved in invasive growth of tumor cells via its receptor MET, a
      protein product of c-met proto-oncogene. HGF activator (HGFA) is a serine
      proteinase responsible for the activation of proform of HGF/SF (proHGF/SF). In
      our study, we examined the effects of engineered expression of HGFA on 2 human
      glioblastoma cell lines (YKG-1 and U251). Both cells expressed MET, while only
      YKG-1 expressed endogenous proHGF/SF. Enhanced MET phosphorylation and increased
      migratory activity were induced by the expression of HGFA in YKG-1 cells in vitro
      in the presence of thrombin, which is a known activator of proHGFA. In contrast,
      MET phosphorylation was consistently observed in U251 that lacked endogenous
      HGF/SF, suggesting ligand-independent activation of MET in this cell line.
      Consequently, the expression of HGFA in U251 did not enhance the MET
      phosphorylation and following cellular response even with the thrombin treatment.
      However, addition of exogenous proHGF/SF resulted in enhanced migratory activity
      of HGFA-expressing U251 cells in the presence of thrombin in vitro. The
      engineered HGFA expression resulted in significantly enhanced tumor growth with
      increased vascular density in vivo when YKG-1 cells were implanted in nude mouse
      brain. This effect was not observed in U251 lacking endogenous proHGF/SF. These
      results indicate the possible existence of multiple mechanisms of MET activation
      in glioblastomas and that the activation system of proHGF/SF is important in
      progression of glioblastomas that express endogenous proHGF/SF and require ligand
      dependent MET activation.

PMID- 16106404
TI  - Interactive effects of high stocking density and food deprivation on carbohydrate
      metabolism in several tissues of gilthead sea bream Sparus auratus.
AB  - The influence of high stocking density (HSD) and food deprivation was assessed on
      carbohydrate metabolism of several tissues of gilthead sea bream Sparus auratus
      for 14 days. Fish were randomly assigned to one of four treatments: (1) fed fish
      under normal stocking density (NSD) (4 kg m(-3)); (2) fed fish under HSD (70 kg
      m(-3)); (3) food-deprived fish under NSD; and (4) food-deprived fish under HSD.
      After 14 days, samples were taken from the plasma, liver, gills, kidney and brain
      for the assessment of plasma cortisol, levels of metabolites and the activity of
      several enzymes involved in carbohydrate metabolism. HSD conditions alone
      elicited important changes in energy metabolism of several tissues that in some
      cases were confirmatory (5-fold increase in plama cortisol, 20% increase in
      plasma glucose, 60% decrease in liver glycogen and 20% increase in gluconeogenic
      potential in the liver) whereas in others provided new information regarding
      metabolic adjustments to cope with HSD in the liver (100% increase in glucose
      phosphorylating capacity), gills (30% decrease in capacity for phosphorylating
      glucose), kidney (80% increase in the capacity of phosphorylating glucose) and
      brain (2.5-fold increase in ATP levels). On the other hand, food deprivation
      alone resulted in increased plasma cortisol, and metabolic changes in the liver
      (enhanced gluconeogenic and glycogenolytic potential of 13% and 18%,
      respectively) and brain (10% increase in glycolytic capacity), confirmatory of
      previous studies, whereas new information regarding metabolic adjustments during
      food deprivation was obtained in the gills and kidney (decreased lactate levels
      in both tissues of 45% and 55%, respectively). Furthermore, the results obtained
      provided, for the first time in fish, information indicating that food
      deprivation increased the sensitivity of gilthead sea bream to the stress induced
      by HSD compared with the fed controls, as demonstrated by increased plasma
      cortisol levels (50% increase vs. fed fish) and a further increase in the
      capacity to export glucose mobilized from liver glycogen stores (70% decrease vs.
      fed fish). These results lend support for a cumulative effect of both stressors
      on plasma cortisol and parameters assessed on carbohydrate metabolism in the
      present experiments, and provide information regarding reallocation of metabolic
      energy to cope with simultaneous stressors in fish.

PMID- 16106405
TI  - Effects of temperature on maximum clinging ability in a diurnal gecko: evidence
      for a passive clinging mechanism?
AB  - The thermal dependence of performance of ectotherms, and particularly locomotor
      performance in lizards, has received much attention. However, only a single study
      has examined the effects of temperature on adhesive clinging ability in geckos,
      despite the importance of adhesion for many pad-bearing lizards and
      invertebrates. We set out to characterize the thermal response of clinging
      ability in the diurnal gecko, Phelsuma dubia in the temperature range of 15-35
      degrees C. Our findings indicate that there is no significant trend in clinging
      ability for P. dubia with temperature and that there is high variation about the
      mean at all temperatures. These findings differ from other whole-organism studies
      of clinging performance and are suggestive of a passive clinging mechanism that
      is dominated by intermolecular van der Waals forces. These findings also suggest
      that clinging ability in this species is not under selective pressures resulting
      from thermal variation, and that P. dubia does not need to regulate body
      temperature closely to maximize clinging ability.

PMID- 16106406
TI  - ACTH-induced stress response during pregnancy in a viviparous gecko: no observed
      effect on offspring quality.
AB  - The typical stress response in reptiles involves the release of corticosterone
      from the adrenal glands. Elevated maternal concentrations of corticosterone in
      mammals during pregnancy may have deleterious effects on offspring fitness, and
      recent work has shown a suppression of the hormonal response to stress during
      pregnancy in rats. Little is known about the influence of reproductive state on
      the secretion of corticosterone in viviparous reptiles or on the effects of high
      levels of corticosterone during reproduction on the developing embryos. We
      examined whether New Zealand common geckos (Hoplodactylus maculatus), pregnant
      with embryos at stages 34-35 of development, secrete corticosterone in response
      to adrenocorticotrophic hormone (ACTH) and whether an ACTH-induced increase in
      maternal corticosterone affects the outcome of pregnancy. Corticosterone
      concentrations in pregnant lizards increased more than seven-fold over basal
      levels following injection of ACTH. However, there were no significant effects of
      elevated corticosterone on the duration or success of pregnancy, or on various
      morphological measures, growth, or sprint speed of the offspring. This may
      reflect a lack of sensitivity of relevant embryonic tissues to corticosterone
      under the conditions of the present experiment or an ability of the embryos to
      bind, degrade, or restrict placental transport of corticosterone. Future studies
      should investigate the possibility of corticosteroid effects on other offspring
      tissues, including effects in adult life.

PMID- 16106407
TI  - Cultivation of the rhabditid Poikilolaimus oxycercus as a laboratory nematode for
      genetic analyses.
AB  - Vulva formation is a paradigm for evolutionary developmental biology in
      nematodes. Not only do the number of vulval precursor cells (VPCs) differ between
      members in the Rhabditidae and Diplogastridae, they are also sculpted via
      different developmental mechanisms, either by cell fusion in most Rhabditidae or
      by programmed cell death in the Diplogastridae. In this context, the species
      Poikilolaimus oxycercus is the only known species in the family Rhabditidae to
      have a subset of the Pn.p cells commit programmed cell death during the
      patterning of the VPCs. Our current study introduces P. oxycercus as a new
      laboratory organism. There are discrete laboratory strains that are genetically
      polymorphic from each other as well as heterogeneous within each strain. In order
      to cultivate this gonochoristic nematode into an experimental model with a
      tractable genetic system, we produced two inbreeding tolerant, near-isogenic
      strains capable of producing viable progeny with each other. We also described P.
      oxycera's morphology by scanning electron microscopy (SEM), basic life history
      traits, hybrid viability, and mating behavior. P. oxycercus females have no
      preference for inter- or intra-strain matings, and can mate with multiple males
      in a relatively short time period, suggesting a propensity for maintaining
      heterozygosity through promiscuity. Interestingly, all sexes from three species
      in the genus Poikilolaimus show five 4',6-diamidino-2-phenylindole (DAPI)
      staining bodies in their germ line cells. This could indicate that Poikilolaimus
      species possess five bivalent chromosomes in their germ lines, in contrast to the
      hermaphroditic Caenorhabditis elegans or Pristionchus pacificus, which have six
      chromosomes.

PMID- 16106408
TI  - Thermoregulatory adaptations of the overwintering captive raccoon dog
      (Nyctereutes procyonoides) in boreal climate.
AB  - The raccoon dog (Nyctereutes procyonoides) is a nocturnal canid thought to
      utilise passive wintering strategy in the boreal climate. To record the deep body
      temperature (T(b)), 12 farmed raccoon dogs were implanted with intra-abdominal
      T(b) loggers on November 26, 2003. Between December 3, 2003 and January 27, 2004
      half of the animals were fasted for 8 weeks. The amplitude of the diurnal T(b)
      oscillations increased due to fasting. However, the mean diurnal T(b) was lower
      in the fasted animals only during two occasions. Unlike observed previously in
      other species, not only did the raccoon dogs experience hypothermia between 0600
      and 1000 hr but also hyperthermia between noon and 1800 hr. The fasted animals
      were as active as the fed animals measured after 42-43 days of fasting and there
      was a significant cross-correlation between physical activity and T(b). The
      nocturnal period of hypothermia is probably an adaptation to save energy during
      food deprivation. The diurnal hyperthermia could be explained by the
      opportunistic foraging behaviour of the species. Opposite to the established
      assumptions, the raccoon dog does not seem to enter winter sleep on fur farms. In
      the future it is important to determine if true winter sleep occurs in nature in
      the species.

PMID- 16106409
TI  - Structure and stability of a model three-helix-bundle protein on tailored
      surfaces.
AB  - The interaction of protein molecules with surfaces is important in numerous
      applications. Theoretical work on protein adsorption has been limited. In
      particular, it is difficult to obtain quantitative predictions about the
      structure and stability of proteins on surfaces. In this study, density-of-states
      based simulations were performed on a Go-like model of a three-helix-bundle
      fragment from protein A (PDB ID: 1bdd). Both mechanical and thermal stability
      were investigated on neutral and attractive surfaces and compared to that in the
      absence of a surface. It was found that attaching the peptide to any type of
      surface decreases its melting temperature by as much as 9 K, depending upon
      orientation. Calorimetric cooperativity, as measured by van't Hoff to
      calorimetric enthalpy ratios, similarly decreased. It was also found that the
      mechanical strength of the peptide attached to surfaces is degraded to varying
      extents, depending upon the surface type and protein orientation. A comparison of
      mechanical and thermal stability showed that the two are not synonymous, but
      occur through different pathways, and that system configurations that are more
      thermally stable are not always so mechanically.

PMID- 16106410
TI  - Paraspermatogenesis in Ceratostoma foliatum (Neogastropoda): confirmation of
      programmed nuclear death.
AB  - Sperm dimorphism, where ejaculates contain both fertile "eusperm" and sterile
      "parasperm", has been implicated in sperm competition in animals. Most parasperm
      lack an acrosome, eliminate the nucleus and develop a complex cytoplasm, swollen
      with secretory vesicles. This study of parasperm in the foliate whelk Ceratostoma
      foliatum, focuses on characterizing the process of nuclear breakdown and the
      nature of cytoplasmic secretions. Testis squash preparations were treated with a
      Promega apoptosis detection [terminal deoxynucleotidyl transferase (TdT)-mediated
      dUTP nick-end labeling-TUNEL] assay (Cedar Lane) to detect nuclear apoptosis;
      acridine orange was used to localize lysosomes. Parasperm were isolated on
      Percoll gradients and their proteins characterized by running electrophoresis of
      lysed, purified fractions on polyacrylamide gels. Results show that the process
      of nuclear breakdown follows the hallmarks of apoptosis in ultrastructure, which
      is confirmed by the presence of 3'-OH overhangs of DNA fragments. This research
      implicates snail parasperm as models for elucidating the nuclear events of
      apoptosis.

PMID- 16106411
TI  - Mothering during early development influences subsequent emotional and social
      behaviour in Japanese quail.
AB  - The aim of the present study was to investigate the influence of mothers on the
      emotional reactivity and social behaviour in young precocial Japanese quail. We
      used a classical method of maternal deprivation. Ethological tests and
      observations analysed and compared the behaviour of young artificially raised
      quail to that of young raised by adoptive maternal quail. After separation from
      mothers, brooded young were more fearful (frightened easily) in the presence of
      humans (human-observer tests) and more neophobic in novel environments (open
      field and hole-in-the-wall tests) than young raised artificially. As chicks
      rarely expressed fear during the brooding period, no differences related to
      mothering could be observed at that time. In separation tests, brooded chicks
      jumped significantly more frequently than non-brooded chicks and later,
      observations of groups revealed that brooded chicks remained closer to one
      another than non-brooded chicks. Social motivation of brooded chicks appeared to
      be higher. These results indicate that, during their first days of life, mothers
      influence the emotional and social behaviour of their young.

PMID- 16106412
TI  - Differential expression of neural and gonadal aromatase enzymatic activities in
      relation to gonadal development in Japanese eel, Anguilla japonica.
AB  - The objectives of the present study were to investigate the enzymatic
      characteristics of brain aromatase in Japanese eel, Anguilla japonica, as well as
      the correlations between aromatase activities in various tissues (brain regions,
      pituitary, and gonads) and ovarian development. Eel brain aromatase exhibited a
      K(m) of 75 nM and a V(max) of 1.14 fmol/min mg protein (91.5 fmol/h mg protein),
      indicating an enzymatic activity much lower than in other teleosts but similar to
      that in mammals. This supports the hypothesis of the occurrence of a single
      aromatase gene in eels (representative of an ancient group of teleosts,
      Elopomorphs), as in mammals, but unlike what is observed in more recent teleosts.
      Aromatase inhibitors could significantly suppress brain and pituitary aromatase
      activity. There was no significant sex difference in aromatase activity in the
      forebrain, midbrain, hindbrain, or pituitary, but there was in the gonads, where
      aromatase could be detected in the ovaries but not in the testes, in accordance
      with the role of this enzyme in ovarian differentiation. Comparison with another
      teleost, black porgy (Percomorph), under the same experimental conditions,
      further confirmed the low activity of aromatase in the eel. We investigated
      variations in brain, pituitary, and gonad aromatase activity in relation to
      ovarian development in control female eels (gonadosomatic index, GSI, 0.1-1.6%)
      as well as in eels treated with pituitary extract (experimental ovarian
      maturation; GSI up to 25%). Differential expression of neural and gonadal
      aromatase was observed in relation to the course of gonadal development.
      Pituitary aromatase activity increased with GSI at all stages. Brain (specially
      forebrain) aromatase activity significantly increased in early vitellogenic
      control eels (GSI>0.8%) and in treated eels. The low activity of eel aromatase
      may be related to the characteristic life cycle of the eel, in which there is a
      long delay of the onset of puberty before oceanic reproductive migration.

PMID- 16106413
TI  - Effect of meiotic maturation on yolk platelet lipids from Bufo arenarum oocytes.
AB  - Progesterone induces the resumption of meiosis in Bufo arenarum full-grown
      arrested oocytes through a nongenomic mechanism called meiotic maturation.
      Growing evidence indicates that lipids are involved in the maturation process.
      They are mainly located in yolk platelets, the principal organelles of amphibian
      oocytes. The aim of the present study was to analyze the effect of progesterone
      induced maturation on lipids from B. arenarum yolk platelets. Ovarian oocytes,
      manually obtained, were incubated with progesterone to induce maturation. Yolk
      platelets were isolated by centrifugation at low velocity. Lipids were separated
      by thin-layer chromatography. For compositional analysis, they were derivatized
      by methanolysis, and were identified and quantified in a gas-liquid
      chromatograph. Phospholipid content decreased in progesterone-treated oocytes,
      mainly as a result of a decrease at the level of phosphatidylcholine (PC). The
      turnover of this lipid is considered crucial for the completion of meiosis.
      Sphingomyelin also underwent a decrease that could be related to the important
      role of ceramide as an inducer of germinal vesicle breakdown. Maturation effect
      on fatty acid composition registered significant changes in PC whose saturated
      fatty acids increased. A net increase in arachidonic acid was observed in
      phosphatidylserine after progesterone treatment. The contents of total
      triacylglycerols and diacylglycerols were not significantly modified by hormone
      effect while free fatty acids underwent a significant increase as a result of
      polyunsaturated fatty acids increase. Altogether, our results demonstrate that
      yolk platelet lipids are involved in the resumption of the meiotic cell cycle,
      thus suggesting that these organelles participate in a dynamic role during
      amphibian development.

PMID- 16106415
TI  - Spectrum of cancers among HIV-infected persons in Africa: the Uganda AIDS-Cancer
      Registry Match Study.
AB  - Although more than 25 million people in sub-Saharan Africa have human
      immunodeficiency virus (HIV) infection, little is known regarding their cancer
      risk. We investigated cancer risk among persons with HIV/AIDS in Uganda using
      record-linkage. We linked records of 12,607 HIV-infected persons attending The
      AIDS Support Organization (TASO) in Kyadondo County from October 1988 through
      December 2002 to the Kampala Cancer Registry. We calculated standardized
      incidence ratios (SIRs) to identify increased cancer risks in the early (4-27
      months after TASO registration), late (28-60 months), or combined (4-60 months)
      incidence periods. We identified 378 cancers (181 prevalent, 197 incident) among
      TASO participants. Of incident cancers, 137 (70%) were AIDS-defining cancers.
      Risk was increased in the early-incident period, compared to the general
      population, for the AIDS-defining cancers: Kaposi sarcoma (SIR 6.4, 95%CI 4.8
      8.4), non-Hodgkin lymphoma (6.7, 1.8-17), and cervical carcinoma (2.4, 1.1-4.4).
      These three cancers were also increased in the combined periods. Risks of five
      non-AIDS-defining cancers were increased in the combined periods: Hodgkin
      lymphoma (5.7, 1.2-17) and cancers of the conjunctiva (SIR 4.0; 1.5-8.7), kidney
      (16, 1.8-58), thyroid (5.7, 1.1-16), and uterus (5.5, 1.5-14). Cancers of the
      breast, nasopharynx, and lung were increased either in the early or late incident
      periods only. Among 407 children, seven cancers were observed, of which five were
      Kaposi sarcoma. The application of a record-linkage design in Africa broadens the
      repertoire of epidemiological tools for studying HIV-infected populations. We
      confirm the increased risks of AIDS-defining cancers and report increased risks
      of a few non-AIDS-defining cancers.

PMID- 16106416
TI  - Performance of the computer algorithm COMPLX for the detection of protein
      complexes in the mass spectra of simulated biological mixtures.
AB  - The performance of the algorithm COMPLX for detecting protein-ligand or other
      macromolecular complexes has been tested for highly complex data sets. These data
      contain m/z values for ions of proteins of the SWISS-PROT database within
      simulated biological mixtures where each component shares a similar molecular
      weight and/or isoelectric point (pI). As many as 1600 ion signals were entered to
      challenge the algorithm to identify ion signals associated with a single protein
      complex that has been ionised and detected within a mass spectrometer. Despite
      the complexity of such data sets, the algorithm is shown to be able to identify
      the presence of individual bimolecular complexes. The output data can be re
      evaluated by the user as necessary in light of any additional information that is
      known concerning the nature of predicted associations, as well as the quality of
      the data-set in terms of errors in m/z values as a direct consequence of the mass
      calibration or resolution achieved. The data presented illustrates that the best
      results are obtained when output results are ranked according to the largest
      continuous series of ion pairs detected for a protein or macromolecule and its
      complex for which the ligand mass is assigned the lowest mass error.

PMID- 16106417
TI  - Radiation-induced gene expression profile of human cells deficient in 8-hydroxy
      2'-deoxyguanine glycosylase.
AB  - The human OGG1 gene encodes a DNA glycosylase that is involved in the base
      excision repair of 8-hydroxy-2'-deoxyguanine (8-OH-dG) from oxidatively damaged
      DNA. Cellular 8-OH-dG levels accumulate in the absence of this activity and could
      be deleterious for the cell. To assess the role of 8-oxoguanine glycosylase
      (OGG1) in the cellular defense mechanism in a specific DNA repair defect
      background, we set out to determine the expression pattern of base excision
      repair genes and other cellular genes not involved in the base excision pathway
      in OGG1-deficient human KG-1 cells after ionizing radiation exposure. KG-1 cells
      have lost OGG1 activity due to a homozygous mutation of Arg229Gln. Gene
      expression alterations were monitored at 4, 8, 12 and 24 hr in 2 Gy irradiated
      cells. Large-scale gene expression profiling was assessed with DNA microarray
      technology. Gene expression analysis identified a number of ionizing radiation
      responsive genes, including several novel genes. There were 2 peaks of radiation
      induced gene induction or repression: one at 8 hr and the other at 24 hr. Overall
      the number of downregulated genes was higher than the number of upregulated
      genes. The highest number of downregulated genes was at 8 hr postirradiation.
      Genes corresponding to cellular, physiologic, developmental and extracellular
      processes were identified. The highest number of radiation-induced genes belonged
      to the signal transduction category, followed by genes involved in transcription
      and response to stress. Microarray gene expression data were independently
      validated by relative quantitative RT-PCR. Surprisingly, none of the genes
      involved in the base excision repair of radiation-induced DNA damage showed
      altered expression.

PMID- 16106418
TI  - Vitamin antioxidants, lipid peroxidation and the systemic inflammatory response
      in patients with prostate cancer.
AB  - The relationship between lipid soluble antioxidant vitamins, lipid peroxidation,
      disease stage and the systemic inflammatory response were examined in healthy
      subjects (n = 14), patients with benign prostate hyperplasia BPH (n = 20),
      localized (n = 40) and metastatic (n = 38) prostate cancer. Prostate cancer
      patients had higher concentrations of malondialdehyde (p < 0.05) and lower
      circulating concentrations of lutein (p < 0.05), lycopene (p < 0.001) and beta
      carotene (p < 0.05). Patients with metastatic prostate cancer, when compared with
      patients having localized disease, had a higher Gleason score (p < 0.01) and had
      more hormonal treatment, but lower concentrations of PSA (p < 0.05), alpha
      tocopherol (p < or = 0.05), retinol (p < 0.01), lutein (p < 0.05) and lycopene (p
      < 0.01). In the prostate cancer patients, PSA was correlated with the
      concentrations of the lipid peroxidation product, malondialdehyde (rs= 0.353, p =
      0.002). C-reactive protein was not correlated with the vitamin antioxidants nor
      malondialdehyde. In contrast, there was a negative correlation between
      malondialdehyde concentrations and both lutein (rs= -0.263, p = 0.020) and
      lycopene (rs= -0.269, p = 0.017). These results indicate that lower
      concentrations of carotenoids, in particular, lycopene reflect disease
      progression rather than the systemic inflammatory response in patients with
      prostate cancer.

PMID- 16106419
TI  - U-2940, a human B-cell line derived from a diffuse large cell lymphoma sequential
      to Hodgkin lymphoma.
AB  - Several patterns of association between Hodgkin and non-Hodgkin lymphomas are
      recognized, some of which support a common cellular origin or shared
      transformation events for both malignancies. We describe the U-2940 cell line
      derived from a diffuse large B-cell lymphoma with some features consistent with
      mediastinal large B-cell lymphoma, clinically apparent 1 month after the initial
      course of chemotherapy for Hodgkin's disease, fulfilling the criteria for
      composite malignancies. U-2940 cells display a mature B phenotype with
      hypermutated IgH rearrangement typical of germinal/postgerminal center origin.
      The cell line is negative for Epstein-Barr virus and no evidence of t(14;18) was
      found. U-2940 cells display multiple chromosomal rearrangements similar to
      recurrent aberrations described in both Hodgkin and non-Hodgkin lymphomas, also
      partially shared by U-2932 derived from a B-cell lymphoma sequential to Hodgkin's
      disease. The original large B-cell lymphoma and the U-2940 cell line bear
      microsatellite instability, an abnormality associated with particular subtypes of
      non-Hodgkin lymphomas and found in tissues involved by Hodgkin lymphoma.
      Therefore, U-2940 cells bear several features known to occur in Hodgkin and in
      non-Hodgkin lymphomas, leading to the assumption that this cell line may
      constitute a useful tool to address elective pathways of lymphomagenesis and
      eventually the Hodgkin and non-Hodgkin lymphoma association.

PMID- 16106420
TI  - MRI and cardiac catheterization: seeing the heart in a new way.

PMID- 16106421
TI  - MRI-guided congenital cardiac catheterization and intervention: the future?
AB  - Over the last 10 years, a number of technological advances have allowed real-time
      magnetic resonance imaging to guide cardiac catheterization, including improved
      image quality, faster scanning times, and open magnets allowing access to the
      patient. Potential advantages include better soft tissue imaging to improve
      catheter manipulation and additional functional information to assist with
      interventional decision-making, all without exposure to ionizing radiation. MRI
      guided diagnostic catheterization, balloon dilation, stent placement, valvar
      replacement, atrial septal defect closure, and radiofrequency ablation all have
      been shown feasible in animal models. MRI-guided catheterization has the
      potential to replace the current X-ray-based diagnostic and interventional
      procedures for children with congenital heart disease, avoiding all radiation
      exposure while improving soft tissue imaging.

PMID- 16106422
TI  - Training and certification for carotid stenting: is the fox guarding the hen
      house?

PMID- 16106423
TI  - Society planning and consensus-building in 2005: where have we been? Where should
      we go next?

PMID- 16106424
TI  - Differential expression of TGFbeta-stimulated clone 22 in normal prostate and
      prostate cancer.
AB  - The transforming growth factor-beta (TGFbeta) superfamily and its downstream
      effector genes are key regulators of epithelial homeostasis. Altered expression
      of these genes may be associated with malignant transformation of the prostate
      gland. The cDNA array analysis of differential expression of the TGFbeta
      superfamily and functionally related genes between patient-matched noncancerous
      prostate (NP) and prostate cancer (PC) bulk tissue specimens highlighted two
      genes, namely TGFbeta-stimulated clone-22 (TSC-22) and Id4. Verification of their
      mRNA expression by real-time PCR in patient-matched NP and PC bulk tissue, in
      laser-captured pure epithelial and cancer cells and in NP and PC cell lines
      confirmed TSC-22 underexpression, but not Id4 overexpression, in PC and in human
      PC cell lines. Immunohistochemical analysis showed that TSC-22 protein expression
      in NP is restricted to the basal cells and colocalizes with the basal cell marker
      cytokeratin 5. In contrast, all matched PC samples lack TSC-22 immunoreactivity.
      Likewise, PC cell lines do not show detectable TSC-22 protein expression as shown
      by immunoblotting. TSC-22 should be considered as a novel basal cell marker,
      potentially useful for studying lineage determination within the epithelial
      compartment of the prostate. Conversely, lack of TSC-22 seems to be a hallmark of
      malignant transformation of the prostate epithelium. Accordingly, TSC-22
      immunohistochemistry may prove to be a diagnostic tool for discriminating benign
      lesions from malignant ones of the prostate. The suggested tumour suppressor
      function of TSC-22 warrants further investigation on its role in prostate
      carcinogenesis and on the TSC-22 pathway as a candidate therapeutic target in PC.

PMID- 16106425
TI  - P53 pathway alterations are uncommon in childhood ependymomas.

PMID- 16106426
TI  - Decrease in LDL receptor-related protein expression and function correlates with
      advanced stages of Wilms tumors.
AB  - BACKGROUND: The molecular processes responsible for the invasive phenotype of
      pediatric Wilms tumors (WT) are poorly understood. A candidate WT suppressor gene
      (WT1) has been found mutated in a number of these pediatric kidney tumors.
      However, the disruption of normal WT1 protein function cannot solely explain WT
      growth. The aim of the present study is to identify new molecular players that
      regulate the invasive character of WT. PROCEDURE: Fresh frozen samples from 45
      renal tumors of Wilms were obtained from the National Wilms Tumor Study Group's
      Biological Samples Bank. Gelatin zymography, Western blotting, and
      immunodetection were used to compare tissue biopsies originating from the
      infiltrating (stage III), metastatic (stage IV), and anaplastic phenotype of
      Wilms tumors (WT). RESULTS: The expression of the low-density lipoprotein
      receptor-related protein (LRP) diminished in stage IV and anaplastic WT.
      Moreover, the expression of RAP, an LRP intracellular chaperone, was also
      decreased. The diminished expression of LRP and RAP correlated with increased
      levels of several known extracellular ligands that LRP usually recycles from the
      extracellular matrix (ECM) environment, including PAI-1, MMP-9, and TIMP-1. The
      proteolytic processing of MT1-MMP, a functional regulator of LRP, also correlated
      with the WT invasive phenotype. CONCLUSIONS: The low expression of LRP, whose
      function is regulated by MT1-MMP and whose activity in recycling ECM-associated
      proteolytic enzymes becomes drastically diminished in advanced stages of WT, may
      in part explain the acquired invasive potential of the developing WT pediatric
      cancer.

PMID- 16106427
TI  - Clinical aspects and treatment of pain in children and adolescents with cancer.
AB  - BACKGROUND: The aim of this study was to characterize the clinical aspects and
      the treatment of mild to severe pain in Brazilian children and adolescents with
      cancer. We evaluated the importance of classifying patients according to the
      phase of cancer treatment (diagnosis, treatment, recurrence, and end-of-life
      palliative care) and the opioid-related side effects. METHODS: An institutional
      prospective study of 184 episodes of pain in children and adolescents with cancer
      was conducted. Pain was classified according to its cause, physiopathology and
      intensity. Treatment was based on the WHO guidelines for cancer pain relief.
      RESULTS: Pain scales were completed by 77% of the patients. Numerical scales were
      used by 49% of them. Morphine was given in 111 episodes for 2,758 patient days.
      Morphine doses had to be escalated when it was given to patients during end-of
      life palliative care. Opioids were well tolerated with no severe side effects.
      Psychological dependence on morphine was found in 2% (2/111) of the cases. Pain
      control was satisfactory in 97% of the episodes. CONCLUSIONS: The WHO guidelines
      for cancer pain relief were effective in controlling pain in children and
      adolescents with cancer. Despite their low socioeconomic level, patients were
      able to quantify their pain using rating scales.

PMID- 16106428
TI  - Painful procedures in children with cancer: comparison of moderate sedation and
      general anesthesia for lumbar puncture and bone marrow aspiration.
AB  - BACKGROUND: The study was conducted to compare moderate sedation (MS) with
      general anesthesia (GA) in the management of frequently performed lumbar puncture
      or bone marrow aspiration (BMA) during the treatment of childhood cancer.
      PROCEDURE: The MS (14 patients for 30 procedures) was managed by non
      anesthesiologists (combined nitrous oxide-midazolam +/- non-pharmacological
      techniques). The GA was managed by anesthesiologists (17 patients for 30
      procedures). A neutral observer recorded side effects, use of sedative
      antagonists, recovery time, oncologist's evaluation, procedure behaviors check
      list (PBCL); subjective perceptions during the procedure with a questionnaire
      administered to children (>6 years) and their parents; drugs costs and
      professional resources. P-values <0.05 were considered significant. RESULTS: We
      had two inadequate sedations in MS (6.6%) versus 0 in GA. We had no significant
      differences in side effects (7.10% MS vs. 8.6% in GA), use of antagonists (2.90%
      GA vs. 0 MS), PBCL, oncologist evaluation and questionnaire data or drugs costs.
      We observed significant differences in recovery times (MS, mean 43 +/- SD min vs.
      GA, mean 117 +/- SD min) and professional resources costs. The effects of non
      pharmacological techniques on anxiety were perceived very positively by both
      children and parents (on 0-4 scale, mean scores 3.57 for the children; 3.53 for
      the parents). CONCLUSIONS: Our study suggests that MS compared favorably to GA
      with respect to both safety and efficacy. When performed by non
      anesthesiologists, MS may be associated with better compliance and cost
      effectiveness as it relies on the contribution of non-pharmacological techniques.

PMID- 16106429
TI  - Familial adenomatous polyposis in two brothers with hepatoblastoma: implications
      for diagnosis and screening.
AB  - Two brothers with hepatoblastoma were noted to have a family history of early
      onset colon cancer. Genetic testing of the younger brother revealed a deletion in
      exon 15 of the adenomatous polyposis coli (APC) gene (2710-2711delAG), consistent
      with a diagnosis of familial adenomatous polyposis (FAP). We review the clinical
      and molecular aspects of the relationship between hepatoblastoma and FAP, and the
      implications for diagnostic testing and cancer screening in affected patients.

PMID- 16106430
TI  - Changes in bone mineral density in survivors of childhood acute lymphoblastic
      leukemia.
AB  - BACKGROUND: There is little information about factors modulating bone mineral
      density (BMD) in survivors of childhood acute lymphoblastic leukemia (ALL).
      PROCEDURE: We analyzed data from 57 survivors (26 male, 52 Caucasian) who
      underwent two serial quantitative computed tomography (QCT) studies of BMD. Using
      multiple linear regression, we evaluated the association of BMD change with
      demographic variables, treatment history, hormone therapy, exercise, and tobacco
      and alcohol use. RESULTS: The median age was 3.4 years (range, 0.9-17.4 years) at
      diagnosis of ALL; the median age at the first QCT (Study I) was 15.0 years
      (range, 10.6-31.0 years) and at the second QCT (Study II) was 18.2 years (range,
      14.2-35.3 years). Mean height increased 4.7 cm and mean weight increased 8.8 kg
      between Studies I and II. While the mean BMD increased 9.33 mg/cc (P = 0.003),
      the BMD Z-score increased only slightly (0.21 SD, P = 0.035). Cortical bone
      density increased significantly (approximately 25.3 mg/cc; P = 0.001), but the
      ratio of trabecular to cortical BMD decreased significantly (P = 0.045). Factors
      independently associated with unfavorable BMD changes included older age at
      diagnosis (P = 0.001), female sex (P = 0.018), and nutritional supplementation
      (0.032). Alcohol (P = 0.009) was an unfavorable factor in a univariable analysis.
      CONCLUSIONS: Bone mineral accretion during adolescence is attenuated in childhood
      ALL survivors by a comparative deficit in trabecular versus cortical bone
      deposition. BMD is influenced favorably by exercise in early adolescence and
      unfavorably by the use of nutritional supplements and alcohol. These results
      provide new information about behavioral factors that affect bone accrual in
      survivors of childhood ALL and warrant definitive evaluation in a larger cohort.

PMID- 16106431
TI  - Papilledema, presenting as reversible loss of vision, in a child with acute
      lymphoblastic leukemia--comment.

PMID- 16106432
TI  - Acute lymphoblastic leukemia presenting in fulminant hepatic failure.
AB  - A previously healthy 4-year-old boy was admitted because of acute liver failure.
      He was icteric, lethargic, had elevated ammonia and abnormal liver function
      tests. Serology was negative for viral hepatitis. There was no history of
      hepatotoxic drugs. Family history was unremarkable. The child was taken to the
      operating room for a living-related hepatic transplant. Frozen section showed
      massive hepatic leukemic infiltration and hepatocellular necrosis. Bone marrow
      aspiration confirmed the diagnosis of acute lymphoblastic leukemia (ALL).
      Transplant was withheld and chemotherapy was attempted. He died the following day
      due to systemic leukemic infiltration, cerebral edema, and severe anoxic ischemic
      encephalopathy.

PMID- 16106433
TI  - Nanoscale topography modulates corneal epithelial cell migration.
AB  - The purpose of this study was to evaluate the effect of surface topographic
      features that mimic the corneal epithelial basement membrane on cell migration.
      We used electron-beam and X-ray lithography and reactive ion etching to pattern
      silicon wafers with pitches (groove width plus ridge width) of nano- and
      microscale dimensions (pitches ranged from 400 to 4000 nm). Additionally,
      polyurethane patterned surfaces were created by replication molding techniques to
      allow for real-time imaging of migrating cells. Individual SV40-transformed human
      corneal epithelial cells frequently aligned with respect to the underlying
      surface patterns and migrated almost exclusively along grooves and ridges of all
      pitches. Direction of migration of individual cells on smooth surfaces was
      random. In cell dispersion assays, colonies of cells migrated out from initially
      circular zones predominantly along grooves and ridges, although there was some
      migration perpendicular to the ridges. On smooth surfaces, cells migrated
      radially, equally in all directions, maintaining circular colony shapes. We
      conclude that substratum features resembling the native basement membrane
      modulate corneal epithelial cell migration. These findings have relevance to the
      maintenance of corneal homeostasis and wound healing, as well as to the evolution
      of strategies in tissue engineering, corneal prosthesis development, and cell
      culture material fabrication.

PMID- 16106434
TI  - The effect of limited lateral resolution in the measurement of implant surface
      roughness: a computer simulation.
AB  - The surface roughness of dental implants affects the bone response elicited.
      Surface roughness is generally described by a range of surface texture
      parameters. The aim of the present study was to use computerized simulation to
      investigate the extent to which the lateral resolution of an instrument/method
      limits the accuracy of certain surface roughness parameters. The lateral
      resolution was defined as the pixel size of a profiling system. A surface
      roughness was simulated by a trigonometric function with random periodicity and
      amplitude. The function was divided into an array of pixels simulating the pixels
      of the profiling system. The mean height value for each pixel was used to
      calculate the surface roughness parameters. It was found that the accuracy of all
      the surface roughness parameters investigated decreased with increasing pixel
      size. This tendency was most pronounced for mean slope and developed length
      ratio; amounting to about 80% of their true values for a pixel size of 20% of the
      true mean high-spot spacing. It was concluded that the lateral resolution of an
      instrument/method severely compromises the precision of surface roughness
      parameters measured for roughness features with a mean high-spot spacing less
      than five times the lateral resolution.

PMID- 16106435
TI  - Interaction of human osteoblasts with bioinert and bioactive ceramic substrates.
AB  - The objective of this study was to compare adhesion, replication, and
      differentiation of human osteoblasts (OPC1 cell line) on two different ceramic
      substrates: a bioinert alumina (A1(2)O(3)), and a bioactive hydroxyapatite (HAp).
      Scanning electron microscopy (SEM) and confocal scanning microscopy were used to
      assess production and distribution of specific osteoblast proteins. Cells grew
      readily on HAp and alumina. On alumina and HAp, OPC1 cells produced distinctive
      cell-to-cell and cell-to-scaffold filopodia and microextensions. OPC1 cells
      proliferated faster on HAp than on alumina substrates. Adhesion was further
      assessed by observing production of the protein vinculin. On alumina, vinculin
      was detected throughout the cytoplasm, with some peripheral punctate regions. On
      HAp, OPC1 cells developed few punctate peripheral regions of vinculin; rather,
      the protein was strongly localized within the cytoplasm. Finally, we measured
      accumulation of the marker osteopontin (OPN). OPN was first detectable on day 5
      and increased through day 11 of culture on alumina. OPC1 cells on HAp produced
      substantial amounts of OPN beginning at day 5, with apparent secretion from the
      cells by culture day 11. These results suggest that the function of osteoblasts
      is strongly affected by the properties of ceramic surfaces, and rapid attachment
      of osteoblasts may result in earlier differentiation on HAp than on alumina.

PMID- 16106436
TI  - Photochemical crosslinking improves the physicochemical properties of collagen
      scaffolds.
AB  - Collagen is a natural biomaterial with excellent biocompatibility. However,
      unprocessed collagen has low stability and weak mechanical strength, which limits
      its application in tissue engineering. The current study aimed to improve the
      physicochemical properties of collagen scaffolds by using photochemical
      crosslinking. Collagen gel was reconstituted and photochemically crosslinked by
      using laser irradiation in the presence of a photosensitizer. Scanning electron
      microscope was used to characterize the surface and cross-sectional morphology.
      Stress-strain relationship and other mechanical properties were determined by
      uniaxial tensile tests. Thermostability and water-binding capacities also were
      analyzed by using differential scanning calorimetry and swelling ratio
      measurements, respectively. Photochemically crosslinked porous structures showed
      fine microstructure with interconnected micron-sized pores, whereas uncrosslinked
      controls only showed macrosheet-like structures. The stabilizing effect of
      photochemical crosslinking also was revealed by retaining the three-dimensional
      lamellae-like structures after thermal analysis in crosslinked membranes but not
      in the controls. Photochemical crosslinking also significantly reduced the
      swelling ratio, improved the stress-strain relationship, peak load, ultimate
      stress, rupture strain, and tangent modulus of collagen membranes. The current
      study showed that an innovative photochemical crosslinking process was able to
      produce collagen scaffolds with fine microstructures; to strengthen, stiffen, and
      stabilize collagen membranes; and to modify their swelling ratio. This may
      broaden the use of collagen-based scaffolds in tissue engineering, particularly
      for weight-bearing tissues.

PMID- 16106437
TI  - Assimilating cell sheets and hybrid scaffolds for dermal tissue engineering.
AB  - Cell sheets can be used to produce neo-tissue with mature extracellular matrix.
      However, extensive contraction of cell sheets remains a problem. We devised a
      technique to overcome this problem and applied it to tissue engineer a dermal
      construct. Human dermal fibroblasts were cultured with poly(lactic-co-glycolic
      acid)-collagen meshes and collagen-hyaluronic acid foams. Resulting cell sheets
      were folded over the scaffolds to form dermal constructs. Human keratinocytes
      were cultured on these dermal constructs to assess their ability to support
      bilayered skin regeneration. Dermal constructs produced with collagen-hyaluronic
      acid foams showed minimal contraction, while those with poly(lactic-co-glycolic
      acid)-collagen meshes curled up. Cell proliferation and metabolic activity
      profiles were characterized with PicoGreen and AlamarBlue assays, respectively.
      Fluorescent labeling showed high cell viability and F-actin expression within the
      constructs. Collagen deposition was detected by immunocytochemistry and electron
      microscopy. Transforming Growth Factor-alpha and beta1, Keratinocyte Growth
      Factor and Vascular Endothelial Growth Factor were produced at various stages of
      culture, measured by RT-PCR and ELISA. These results indicated that assimilating
      cell sheets with mechanically stable scaffolds could produce viable dermal-like
      constructs that do not contract. Repeated enzymatic treatment cycles for cell
      expansion is unnecessary, while the issue of poor cell seeding efficiency in
      scaffolds is eliminated.

PMID- 16106438
TI  - In vivo effects of RGD-coated titanium implants inserted in two bone-gap models.
AB  - RGD (Arg-Gly-Asp) coating has been suggested to enhance implant fixation by
      facilitating the adhesion of osteogenic cells to implant surfaces. Orthopedic
      implants are unavoidably surrounded partly by gaps, and these regions represent a
      challenging environment for osseointegration. We examined the effects of cyclic
      RGD-coated implants on tissue integration and implant fixation in two cancellous
      bone-gap models. In canines, we inserted loaded RGD-coated implants with 0.75-mm
      gap (n = 8) and unloaded RGD-coated implants with 1.5-mm gap (n = 8) into the
      distal femur and proximal tibia, respectively. Control gap implants without RGD
      were inserted contralaterally. The titanium alloy (Ti-6Al-4V) implants were
      plasma sprayed and cylindrical. The observation period was 4 weeks and the
      fixation was evaluated by push-out test and histomorphometry. Mechanical implant
      fixation was improved for RGD-coated implants. Unloaded RGD-coated implants
      showed a significant increase in bone whereas both loaded and unloaded implants
      showed a significant reduction in fibrous tissue anchorage. The results are
      encouraging, because RGD had an overall positive effect on the fixation of
      titanium implants in regions where gaps exist with the surrounding bone. RGD
      peptide coatings can potentially be used to enhance tissue integration in these
      challenging environments.

PMID- 16106439
TI  - Fibrillar assembly and stability of collagen coating on titanium for improved
      osteoblast responses.
AB  - Collagen, as a major constituent of human connective tissues, has been regarded
      as one of the most important biomaterials. As a coating moiety on Ti hard-tissue
      implants, the collagen has recently attracted a great deal of attention. This
      article reports the effects of fibrillar assembly and crosslinking of collagen on
      its chemical stability and the subsequent osteoblastic responses. The fibrillar
      self-assembly of collagen was carried out by incubating acid-dissolved collagen
      in an ionic-buffered medium at 37 degrees C. The degree of assembly was varied
      with the incubation time and monitored by the turbidity change. The differently
      assembled collagen was coated on the Ti and crosslinked with a carbodiimide
      derivative. The partially assembled collagen contained fibrils with varying
      diameters as well as nonfibrillar aggregates. On the other hand, the fully
      assembled collagen showed the complete formation of fibrils with uniform
      diameters of approximately 100-200 nm with periodic stain patterns within the
      fibrils, which are typical of native collagen fibers. Through this fibrillar
      assembly, the collagen coating had significantly improved chemical stability in
      both the saline and collagenase media. The subsequent crosslinking step also
      improved the stability of the collagen coating, particularly in the unassembled
      collagen. The fibrillar assembly and the crosslinking of collagen significantly
      influenced the osteoblastic cell responses. Without the assembly, the collagen
      layer on Ti adversely affected the cell attachment and proliferation. However,
      those cellular responses were improved significantly when the collagen was
      assembled to fibrils and the assembly degree was increased. After crosslinking
      the collagen coating, these cellular responses were significantly enhanced in the
      case of the unassembled collagen but were not altered much in the assembled
      collagen. Based on these observations, it is suggested that the fibrillar
      assembly and the crosslinking of collagen require careful considerations in the
      collagen administration as a coating moiety.

PMID- 16106440
TI  - Fabrication and characteristics of bioactive sodium titanate/titania graded film
      on NiTi shape memory alloy.
AB  - A bioactive sodium titanate/titania graded film was formed in situ on NiTi shape
      memory alloy (SMA) by oxidizing in H(2)O(2) solution and subsequent NaOH
      treatment and characterized by scanning electron microscopy, Raman spectroscopy,
      X-ray diffraction, Fourier transform infrared spectroscopy, and X-ray
      photoelectron spectroscopy (XPS). The bioactivity of the film was investigated
      using a simulated body fluid (SBF) soaking test. A titania (TiO(2)) layer was
      first found on NiTi substrate after oxidized in H(2)O(2) solution, and then a
      porous sodium titanate (Na(2)TiO(3))/titania film with many Ti--OH groups and a
      trace of Ni(2)O(3) was formed by the reaction of partial TiO(2) phase with NaOH
      solution. After immersion in SBF for 12 h, apatite was observed to nucleate and
      grow on the film. With longer soaking time, more apatite appeared on its surface
      but our control experiments didn't reveal any apatite formation on the chemically
      polished NiTi SMA, which indicates the bioactivity of NiTi implants could be
      improved by the formation of the bioactive film. Moreover, XPS depth profiles of
      O, Ni, Ti, and Na show the bioactive film possesses a smooth graded interface
      structure to NiTi substrate, which is in favor of sufficient mechanical stability
      of apatite layer by subsequent deposition in SBF.

PMID- 16106441
TI  - Synergistic DNA damage and lipid peroxidation in cultured human white blood cells
      exposed to 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone and ultraviolet A.
AB  - 4-(Methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen
      in cigarette smoke, while ultraviolet (UV) irradiation from sunlight is a major
      factor for causing skin aging and skin cancer. However, little is known about the
      effects of the interaction between NNK and UV light on the induction of DNA
      damage and oxidative stress. In this study, we incubated human white blood cells
      (WBCs) with NNK, followed by irradiating the cells with ultraviolet A (UVA) (320
      380 nm), and we measured DNA strand breaks (by the Comet or single-cell gel
      electrophoresis assay), lipid peroxidation (as thiobarbituric acid-reactive
      substances, TABRS), and the levels of intracellular reactive oxygen species
      (ROS). We found that preincubation with 1.0 mM NNK, followed by UVA irradiation
      (7.6 kJ/m2) synergistically increased DNA damage, lipid peroxidation, and the
      level of intracellular ROS in WBCs, while NNK or UVA alone had little or no
      effect. Electron spin resonance spectroscopic analyses showed that NNK plus UVA
      enhanced the UVA-induced generation of singlet oxygen but not hydroxyl radicals.
      In addition to ROS, bioactivation of NNK by cytochromes P450 (CYP) to form
      reactive NNK intermediates may also be involved in the synergistic damage to WBCs
      by NNK plus UVA. This is evidenced by the synergistic increase in N7
      methylguanine (7-mGua), a major DNA adduct produced by NNK. Overall, the present
      study demonstrates that exposure of WBCs to both NNK and UVA synergistically
      increases DNA damage and lipid peroxidation and that such effects involve
      enhanced generation of ROS, especially singlet oxygen, and activation of NNK to 7
      mGua by CYP. The results imply that NNK is a phototoxic agent.

PMID- 16106442
TI  - MX, a by-product of water chlorination, lacks in vivo genotoxicity in gpt delta
      mice but inhibits gap junctional intercellular communication in rat WB cells.
AB  - 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a by-product of water
      chlorination, is a potent bacterial mutagen and rat carcinogen. In the present
      study, the in vivo mutagenicity, cell proliferative activity, and carcinogenicity
      of MX were investigated in gpt delta mice. Groups of 5 male and female 7-week-old
      gpt delta C57BL/6J transgenic mice were given MX at doses of 0, 10, 30, or 100
      ppm in their drinking water for 12 weeks, and then killed to assess in vivo
      mutagenicity using 6-thioguanine and Spi- selection, and cell proliferative
      activity using immunohistochemistry for proliferating cell nuclear antigen
      (PCNA). Further groups of 10 male and female gpt delta mice were given 0 or 100
      ppm MX for 78 weeks, and a full necropsy with histopathological examination of
      all organs was conducted to detect neoplastic lesions. The 12-week MX treatment
      did not result in mutagenicity in the livers or lungs or cell proliferative
      activity in several organs of the mice, and the 78-week treatment did not cause
      carcinogenicity. Additional investigations were conducted to evaluate the
      potential of MX to inhibit gap junctional intercellular communication (GJIC) in
      rat liver epithelial cells (WB cells) by the scrape loading/dye transfer method.
      Inhibition of GJIC was detected within 2 hr with a noncytotoxic dose of MX (4
      microg/ml), followed by partial restoration after 5 hr. A second phase of
      inhibition occurred after 10 hr and then the lowered level persisted for the 24
      hr-incubation period. Dose-dependent inhibition was evident at both 2 hr and 24
      hr, with much stronger effects at the former time. These findings indicate that
      MX is not mutagenic, mitogenic or carcinogenic in mice, and suggest that the
      compound exerts epigenetic actions leading to GJIC inhibition.

PMID- 16106443
TI  - A sensitive biochemical assay for the detection of uracil.
AB  - We have developed a sensitive new assay for the detection of uracil in DNA. The
      assay described here is an adaptation to the highly sensitive aldehydic slot blot
      (ASB) assay developed by Nakamura et al. (Nakamura et al. 1998: Cancer Res 58:222
      225) in which aldehydic DNA lesions (ADLs) are detected through binding of a
      biotinylated aldehydic reactive probe to DNA. The uracil DNA glycosylase (UDG)
      coupled ASB assay uses uracil-DNA glycosylase to generate an abasic site, which
      is subsequently detected by the ASB methodology. The ability to modify this
      technique for the detection of uracil has these advantages: small quantities of
      DNA are required (4 microg of DNA); the assay is adaptable to DNA from both cells
      and tissues; sensitivity is as good as that achieved by less accessible
      methodologies, like gas chromatography-mass spectroscopy (GC-MS); DNA strand
      breaks are not a confounding variable; preexisting aldehydic lesions are blocked
      through the use of methoxyamine; variation is very low (<3%); radioactive
      isotopes are not required; and the assay is easy to establish and involves only
      equipment and reagents that are inexpensive and readily available. This assay is
      conceivably adaptable to the detection of other DNA base lesions through the use
      of a variety of DNA glycosylases.

PMID- 16106444
TI  - Maternal diseases and isolated orofacial clefts in Hungary.
AB  - BACKGROUND: Isolated orofacial clefts (OFCs) are likely to be caused by gene
      environment interaction; therefore, the objective of the current study was to
      evaluate the possible association between all maternal diseases during pregnancy
      and isolated cleft lip with or without cleft palate (CL+/-CP) and posterior cleft
      palate (PCP) in the offspring. METHODS: The database of the large population
      based Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996,
      was evaluated. The database includes 1374 cases with isolated CL+/- CP and 601
      with PCP, plus 38,151 matched population controls (without defects) and 20,868
      patient controls with other defects. Data collection was based on prospective
      medical records, retrospective maternal data via a self-reported questionnaire,
      and home visits of nonresponding families. RESULTS: An increased risk for
      isolated CL+/- CP was found for children born to mothers with influenza, common
      cold, orofacial herpes, and gastroenteritis during pregnancy. Risk for isolated
      PCP was increased in children of mothers with influenza, sinusitis, and
      bronchitis. Among chronic maternal diseases, epilepsy and angina pectoris showed
      a higher prevalence in the mothers of children born with isolated OFCs (cases).
      CONCLUSIONS: Some maternal diseases are risk factors for the pathogenesis of
      isolated OFCs. It is worth considering the prevention of possible harmful effects
      of influenza by vaccination during the expected epidemic period.

PMID- 16106445
TI  - Temperature-dependent structural and functional features of a hyperthermostable
      enzyme using elastic neutron scattering.
AB  - The dynamic behavior of an endoglucanase from the hyperthermophilic microorganism
      Pyrococcus furiosus was investigated using elastic neutron scattering. The
      temperature dependence of the atomic motions was correlated with conformational
      and functional characteristics of the enzyme. The onset of biological function at
      temperatures higher than approximately 25 degrees C (the hyperthermostable enzyme
      is essentially inactive at room temperature) was associated with a dynamical
      transition in the anharmonic motions domain. This transition from the nonactive
      to the enzymatically active conformation involved structurally similar
      conformational substates in the energy landscape. From the mean-square
      displacement of the protein atoms, the molecular flexibility and the effective
      force constants were calculated at different temperature zones. The results
      showed that the activity increases at higher temperatures where the
      intramolecular bonds are weakened and the overall rigidity of the protein is
      decreased. Further temperature increase resulted in significantly increased
      atomic fluctuations featuring heat denaturation of the protein.

PMID- 16106446
TI  - The number of CD34(+) cells in peripheral blood as a predictor of the CD34(+)
      yield in patients going to autologous stem cell transplantation.
AB  - The number of CD34(+) cells in peripheral blood (PB) is a guide to the optimal
      timing to harvest peripheral blood progenitor cells (PBPC). The objective was to
      determine the number of CD34(+) cells in PB that allows achieving a final
      apheresis product containing > or =1.5 x 10(6) CD34(+) cells/kg, performing up to
      three aphereses. Between March 1999 and August 2003, patients with hematological
      and solid malignancies who underwent leukapheresis for autologous bone marrow
      transplantation were prospectively evaluated. Seventy-two aphereses in 48
      patients were performed (mean 1.45 per patient; range 1-3). PBPC were mobilized
      with cyclophosphamide plus recombinant human granulocyte-colony stimulating
      factor (G-CSF) (n = 40), other chemotherapy drugs plus G-CSF (n = 7), or G-CSF
      alone (n = 1). We found a strong correlation between the CD34(+) cells count in
      peripheral blood and the CD34(+) cells yielded (r = 0.903; P < 0.0001). Using
      receiver-operating characteristic (ROC) curves, the minimum number of CD34(+)
      cells in PB to obtain > or =1.5 x 10(6)/kg in the first apheresis was 16.48
      cells/microL (sensitivity 100%; specificity 95%). The best cut-off point
      necessary to obtain the same target in the final harvest was 15.48 cells/microL,
      performing up to three aphereses (sensitivity 89%; specificity 100%). In our
      experience, > or =15 CD34(+) cells/microL is the best predictor to begin the
      apheresis procedure. Based on this threshold level, it is possible to achieve at
      least 1.5 x 10(6)/kg CD34(+) cells in the graft with < or =3 collections.

PMID- 16106447
TI  - LIGHTing up dendritic cell activation: Immune regulation and viral exploitation.
AB  - The maturation state of dendritic cells (DC) is regulated by a variety of
      factors. These include ligands expressed by T cells, such as members of the TNF
      superfamily. Recent studies have highlighted the role of one such molecule,
      LIGHT, as a positive regulator of DC biology, promoting the maturation of these
      cells through the activation of NF-kappaB pathways. In addition, HSV-1 envelope
      glycoproteins can also bind the LIGHT receptor, herpes virus entry mediator
      (HVEM), and activate similar downstream signalling pathways in DC. The
      consequence of this host-viral interaction may be a novel pathway of viral immune
      evasion.

PMID- 16106448
TI  - Assembly of MYPT1 with protein phosphatase-1 in fibroblasts redirects
      localization and reorganizes the actin cytoskeleton.
AB  - Dephosphorylation of actin-binding proteins by a specialized form of protein
      Ser/Thr phosphatase type-1 (PP1) regulates smooth muscle contraction and
      morphology and motility of nonmuscle cells. This myosin and ezrin/radixin/moesin
      (ERM)-targeted phosphatase comprises the delta isoform PP1 catalytic subunit plus
      a primary regulatory subunit called myosin phosphatase targeting (MYPT1). We
      reconstructed myosin/ERM phosphatase in living rat embryo fibroblasts (REF52
      cells) by transient expression of epitope-tagged MYPT1 (myc-MYPT1) plus HA-tagged
      PP1. Unexpectedly, wild-type myc-MYPT1 expressed alone accumulated predominantly
      in the nucleus, as visualized by immunofluorescent microscopy, whereas if
      coexpressed with HA-PP1, it was localized in the cytosol and deposited on
      cytoskeleton myofilaments. The F38A mutation of MYPT1 that eliminates PP1 binding
      gave nuclear localization of myc-MYPT1, even when coexpressed with HA-PP1. Thus,
      expression of both subunits was necessary to form myosin/ERM phosphatase in situ
      and mediate myofilament localization. The results indicate there is little
      endogenous PP1 available for interaction or interchange with ectopic regulatory
      subunits in living cells. We concluded that myosin binding by the C-terminal
      domain of MYPT1 is not sufficient to override nuclear import in fibroblasts, but
      the binding of PP1 to myc-MYPT1 neutralizes nuclear import. Full-length myc-MYPT1
      plus HA-PP1 induced only subtle changes in organization of the actin
      cytoskeleton, however coexpression of myc-MYPT1(1-300) with HA-PP1 dispersed
      stress fibers without major alteration in morphology and myc-MYPT1(1-498)
      disrupted the cytoskeleton and produced radically extended cells that appeared
      like neurons. Based on these responses, we conclude that the MYPT1 C-terminus
      functions as an auto-inhibitory domain, and a central domain in MYPT1 can mediate
      extensive reorganization of the actin cytoskeleton.

PMID- 16106449
TI  - Differences in morphology of phagosomes and kinetics of acidification and
      degradation in phagosomes between the pathogenic Entamoeba histolytica and the
      non-pathogenic Entamoeba dispar.
AB  - Phagocytosis plays an important role in the pathogenicity of the intestinal
      protozoan parasite Entamoeba histolytica. We compared the morphology of
      phagosomes and the kinetics of phagosome maturation using conventional light and
      electron microscopy and live imaging with video microscopy between the virulent
      E. histolytica and the closely-related, but non-virulent E. dispar species.
      Electron micrographs showed that axenically cultivated trophozoites of the two
      Entamoeba species revealed morphological differences in the number of bacteria
      contained in a single phagosome and the size of phagosomes. Video microscopy
      using pH-sensitive fluorescein isothiocynate-conjugated yeasts showed that
      phagosome acidification occurs within 2 min and persists for >12 h in both
      species. The acidity of phagosomes significantly differed between two species
      (4.58 +/- 0.36 or 5.83 +/- 0.38 in E. histolytica or E. dispar, respectively),
      which correlated well with the differences in the kinetics of degradation of
      promastigotes of GFP-expressing Leishmania amazonensis. The acidification of
      phagosomes was significantly inhibited by a myosin inhibitor, whereas it was only
      marginally inhibited by microtubules or actin inhibitors. A specific inhibitor of
      vacuolar ATPase, concanamycin A, interrupted both the acidification and
      degradation in phagosomes in both species, suggesting the ubiquitous role of
      vacuolar ATPase in the acidification and degradation in Entamoeba. In contrast,
      inhibitors against microtubules or cysteine proteases (CP) showed distinct
      effects on degradation in phagosomes between these two species. Although
      depolymerization of microtubules severely inhibited degradation in phagosomes of
      E. histolytica, it did not affect degradation in E. dispar. Similarly, the
      inhibition of CP significantly reduced degradation in phagosomes of E.
      histolytica, but not in E. dispar. These data suggest the presence of biochemical
      or functional differences in the involvement of microtubules and proteases in
      phagosome maturation and degradation between the two species.

PMID- 16106450
TI  - Three-dimensional reconstruction of axonemal outer dynein arms in situ by
      electron tomography.
AB  - We present here for the first time a 3D reconstruction of in situ axonemal outer
      dynein arms. This reconstruction has been obtained by electron tomography applied
      to a series of tilted images collected from metal replicas of rapidly frozen,
      cryofractured, and metal-replicated sperm axonemes of the cecidomid dipteran
      Monarthropalpus flavus. This peculiar axonemal model consists of several
      microtubular laminae that proved to be particularly suitable for this type of
      analysis. These laminae are sufficiently planar to allow the visualization of
      many dynein molecules within the same fracture face, allowing us to recover a
      significant number of equivalent objects and to improve the signal-to-noise ratio
      of the reconstruction by applying advanced averaging protocols. The 3D model we
      obtained showed the following interesting structural features: First, each dynein
      arm has two head domains that are almost parallel and are obliquely oriented with
      respect to the longitudinal axis of microtubules. The two heads are therefore
      positioned at different distances from the surface of the A-tubule. Second, each
      head domain consists of a series of globular subdomains that are positioned on
      the same plane. Third, a stalk domain originates as a conical region from the
      proximal head and ends with a small globular domain that contacts the B-tubule.
      Fourth, the stem region comprises several globular subdomains and presents two
      distinct points of anchorage to the surface of the A-tubule. Finally, and most
      importantly, contrary to what has been observed in isolated dynein molecules
      adsorbed to flat surfaces, the stalk and the stem domains are not in the same
      plane as the head.

PMID- 16106451
TI  - Evidence-based apheresis.

PMID- 16106452
TI  - Rheopheresis for macular degeneration: the data is not there yet to justify it.

PMID- 16106453
TI  - Rheopheresis for dry AMD: controversy requiring mutual respect.

PMID- 16106454
TI  - 2005 A.J. Ladman AAA/Wiley Exemplary service award: Dr. Stephen Carmichael.

PMID- 16106455
TI  - Ge2 trapped by triple bonds between two metal centers: the germylidyne complexes
      trans,trans-[Cl(depe)2M[triple chemical bond]Ge--Ge[triple chemical
      bond]M(depe)2Cl] (M=Mo, W) and bonding analyses of the M[triple chemical bond]Ge-
      Ge[triple chemical bond]M chain.

PMID- 16106456
TI  - Camouflaged carborarods derived from B-permethyl-1,12-diethynyl-para- and B
      octamethyl-1,7-diethylnyl-meta-carborane modules.
AB  - Rigid camouflaged carborarods constructed from the corresponding C,C'-diethynyl
      derivatives of B-decamethyl-1,12-dicarbadodecaborane(12) (6) and B-octamethyl-1,7
      dicarbadodecaborane(12) (48) have been synthesized by largely conventional
      organic transformations. These carborarods are the longest discrete rod species
      available by this method in which B-methylated p-carborane and m-carborane cages
      are linked through their carbon vertices by using butadiynylene moieties. They
      exhibit enhanced solubility in common organic solvents relative to all other
      presently known carborane-based rigid-rod molecules. The oxidative coupling of
      bis(ethynyl) derivatives of 6 generates oligomers containing, on average, 16
      carborane modules. The structural characterization of the corresponding dimeric
      species revealed that the carborarods possess a sinusoidal chain distortion in
      the solid state. The stereoelectronic properties of these and related model
      carborarods were evaluated by using molecular dimensions as a monitor for the
      comparison of computational and experimental methods. In addition, the effect of
      exhaustive B-methylation of 12- and 10-vertex para-carborane cages in a series of
      model C,C'-diethynyl derivatives was similarly investigated by computational and
      structural studies. As expected, a correlation of intercage C--C bond lengths
      with cage size was observed and was attributed to hybridization effects. B
      Permethylation had no significant structural effect with either 10- or 12-vertex
      cage derivatives. Relative to unsubstituted compounds, thermal and chemical
      stabilities of B-permethylated derivatives were increased through the operation
      of a steric "bumper-car" process, and solubilities in organic solvents were
      enhanced. The formation of linear, sterically encumbered platina-carborarods
      using ethynyl derivatives of 6 as precursors is described.

PMID- 16106457
TI  - On the formation of aliphatic polycarbonates from epoxides with chromium(III) and
      aluminum(III) metal-salen complexes.
AB  - A DFT-based description is given of the CO2/epoxide copolymerization with a
      catalyst system consisting of metal (chromium, iron, titanium, aluminum)-salen
      complexes (salen = N,N'-bis(3,5-di-tert-butylsalicyliden-1,6-diaminophenyl) in
      combination with either chloride, acetate, or dimethylamino pyridine (DMAP) as
      external nucleophile. Calculations indicate that initiation proceeds through
      nucleophilic attack at a metal-coordinated epoxide, and the most likely
      propagation reaction is a bimolecular process in which a metal-bound nucleophile
      attacks a metal-bound epoxide. Carbon dioxide insertion occurs at a single metal
      center and is most likely the rate-determining step at low pressure. The
      prevalent chain terminating/degradation-the so-called backbiting, a reaction
      leading to formation of cyclic carbonate from the polymer chain-would involve
      attack of a carbonate nucleophile rather than an alkoxide at the last unit of the
      growing chain. The backbiting of a free carbonato chain end is particularly
      efficient. Anion dissociation from six-coordinate aluminum is appreciably easier
      than from chromium-salen complexes, indicating the reason why in the former case
      cyclic carbonate is the sole product. Experimental data were gathered for a
      series of chromium-, aluminum-, iron-, and zinc-salen complexes, which were used
      in combination with external nucleophiles like DMAP and mainly (tetraalkyl
      ammonium) chloride/acetate. Aluminum complexes transform PO (propylene oxide) and
      CO2 to give exclusively propylene carbonate. This is explained by rapid carbonate
      anion dissociation from a six-coordinate complex and cyclic formation. CO2
      insertion or nucleophilic attack of an external nucleophile at a coordinated
      epoxide (at higher CO2 pressure) are the rate-determining steps. Catalysis with
      [Cr(salen)(acetate/chloride)] complexes leads to the formation of both cyclic
      carbonate and polypropylene carbonate with various quantities of ether linkages.
      The dependence of the activity and selectivity on the CO2 pressure, added
      nucleophile, reaction temperature, and catalyst concentration is complex. A
      mechanistic description for the chromium-salen catalysis is proposed comprising a
      multistep and multicenter reaction cycle. PO and CO2 were also treated with
      mixtures of aluminum- and chromium-salen complexes to yield unexpected ratios of
      polypropylene carbonate and cyclic propylene carbonate.

PMID- 16106458
TI  - Theoretical study of the remote control of hydrogen bond strengths in donor
      bridge-acceptor systems: principles for designing effective bridges with
      substituent tuning.
AB  - Remote control of hydrogen bond strengths has been studied based on conjugated
      donor-bridge-acceptor (pyrrole-bridge-imine) systems. The neutral and protonated
      states of the imine can change the hydrogen bonding ability of the pyrrole
      because, in the protonated state, significant partial intramolecular charge
      transfer (ICT) is induced that causes partial delocalization of the positive
      charge onto the pyrrole moiety. An efficient bridge, regardless of its length,
      should help electrons to flow out of pyrrole. A previously developed design
      strategy for the bridge (low bridge HOMO/LUMO) leads to the study of cyano- and
      fluoro-substituted conjugated systems. Substitution positions are found to be of
      key importance for maximizing the protonation-induced response from the donor
      bridge-acceptor systems. Our results not only help to identify useful bridge
      substitution patterns, but also highlight interesting issues regarding the bridge
      conformation and the fluorine lone-pair effect.

PMID- 16106459
TI  - Self-assembled peptide tubelets with 7 A pores.
AB  - Here we report the preparation and structural characteristics of self-assembling
      peptide tubelets composed of 32-membered rings formed of alternating alpha-amino
      acids and cis-3-aminocyclohexanecarboxylic acids. The tubelets possess a partial
      hydrophobic core environment, provided by the projection of the cyclohexane C2
      methylene moiety into the lumen, and a Van der Waals pore diameter of about 7 A.

PMID- 16106460
TI  - Ion-triggered multistate molecular switching device based on regioselective
      coordination-controlled ion binding.
AB  - Molecular devices capable of accessing different controlled conformational
      states, while optically signaling the occupied state, are attractive tools for
      nanotechnology since they relate to both areas of molecular mechanical devices
      and logic gates. We report here a simple molecular system that allows access to
      four distinct conformational and optical states. It is based on the
      regioselective complexation of metal ions to a heterocyclic ligand triad, which
      is dictated by the accessible coordination geometry and electrostatic properties
      of two distinct binding subunits. Thus, local conformational switching is brought
      about by tetrahedral coordination (of Cu(I)) or octahedral coordination (of M(2+)
      ions) to bidentate and tridentate binding subunits, respectively. The shape
      modifications undergone represent an ion-controlled nanomechanical device. They
      give controlled access to four different states that display different physico
      chemical (e.g. optical) properties and provide a basis for logic gate operations.

PMID- 16106461
TI  - First generation and trapping of a dehydrometallophthalocyanine starting from
      triazole-functionalized zinc phthalocyanine.
AB  - Direct 1N-amination of the triazole-fused zinc phthalocyanine 2 and oxidation of
      the formed amino derivative 3 resulted in the generation of the very reactive
      intermediate, the dehydrometallophthalocyanine 4, which was not known previously.
      The latter was trapped in situ with different dienes, for example, furan,
      tetraphenylcyclopentadienone, and anthracene to form the corresponding Diels
      Alder adducts. The products were characterized by 1H and 13C-dept135 NMR, and
      UV/Vis spectroscopy, MALDI-TOF mass spectrometry, and elemental analysis, which
      are fully in agreement with their structure. The developed synthetic procedure
      opens a simple and versatile pathway towards unsymmetrical peripheral
      modification of phthalocyanines, which is readily applicable to the micromol
      scale and is important for the design of new interesting Pc-based systems.

PMID- 16106462
TI  - Crystal engineering: toward intersecting channels from a neutral network with a
      bcu-type topology.

PMID- 16106463
TI  - Synthesis of stable aragonite superstructures by a biomimetic crystallization
      pathway.

PMID- 16106464
TI  - A dendron based on natural amino acids: synthesis and behavior as an
      organogelator and lyotropic liquid crystal.

PMID- 16106465
TI  - Reversible conversion of conducting polymer films from superhydrophobic to
      superhydrophilic.

PMID- 16106466
TI  - Preparation of heterobimetallic oxide-hydroxide-hydrogensulfides [LAl(OH)(mu
      O)MCp2(SH)] (M=Ti, Zr).

PMID- 16106467
TI  - Tautomers of one-electron-oxidized guanosine.

PMID- 16106468
TI  - Gastric cancer in the East: same disease, different patient.

PMID- 16106469
TI  - Colonoscopic surveillance and clinical genetics services.

PMID- 16106470
TI  - Human T helper (Th) cell lineage commitment is not directly linked to the
      secretion of IFN-gamma or IL-4: characterization of Th cells isolated by FACS
      based on IFN-gamma and IL-4 secretion.
AB  - Upon activation in vitro, only a fraction of the bulk human T helper cell
      cultures secret the hallmark Th1/2 cytokines (IFN-gamma for Th1 and IL-4 for Th2,
      respectively). It is uncertain whether these IFN-gamma-/IL-4- cells are
      differentiated Th1 or Th2 cells. Here, we have characterized live IFN-gamma+, IL
      4+ and IFN-gamma-/IL-4- cells isolated from Th cell cultures treated under Th1 or
      Th2 polarizing conditions by employing affinity matrix capture technology. RNA
      samples from the sorted cells were analyzed by real time RT-PCR and microarrays.
      The double negative cells from either Th1 or Th2 cultures expressed lower levels
      of Th1/Th2 marker cytokine genes (IFNgamma, IL4, and IL5). However, they were
      comparable with the IFN-gamma+ or IL-4+ cells in the expression levels of other
      Th1/Th2 marker genes (GATA3, Tbet, and IL12Rbeta2). Most importantly, these
      double negative cells were already committed in their Th1/Th2 lineages. Gene
      expression profiling analysis showed that very few previously identified Th1/Th2
      marker genes were differentially expressed between the IFN-gamma or IL-4
      producers and the non-producers, further underscoring the similarity between
      these two groups.

PMID- 16106471
TI  - Diagnostic peritoneal lavage--an obituary (Br J Surg 2005; 92: 517-518).

PMID- 16106472
TI  - How do patients who participate in cancer support groups differ from those who do
      not?
AB  - Research has shown that cancer patients in general benefit from support group
      participation. However, few patients attend such groups. This study investigated
      differences between participants of a community cancer support group and a random
      selection of non-participants from the Cancer Registry. Data were collected
      through mail survey, and included variables identified through past research and
      variables derived from Leventhal's self-regulatory model of illness
      representations and the theory of planned behaviour. Sixty-three support group
      participants and 44 comparison sample respondents were recruited. Support group
      participants were more likely to be female, without a partner, younger, and to
      have more education and formal support than non-participants. They held more
      favourable views of support groups, believed that significant others were
      favourable towards participation, and perceived less difficulty in joining a
      group. They furthermore used more active, adaptive coping strategies and felt
      more control over their cancer, but were more distressed and anxious. Non
      participants reported more support from a special person. A multivariate logistic
      regression analysis showed only psychosocial variables to be independent
      predictors of participation. As psychological variables are amenable to change,
      increase of appropriate support group participation should be possible, for
      instance by addressing patients' beliefs about support groups.

PMID- 16106473
TI  - Diagnostic peritoneal lavage--an obituary (Br J Surg 2005; 92: 517-518).

PMID- 16106474
TI  - Diagnostic peritoneal lavage--an obituary (Br J Surg 2005; 92: 517-518).

PMID- 16106475
TI  - Diagnostic peritoneal lavage--an obituary (Br J Surg 2005; 92: 517-518).

PMID- 16106476
TI  - 1H and 13C NMR signal assignment of synthetic (-)-methyl thyrsiflorin B acetate,
      (-)-thyrsiflorin C and several scopadulane derivatives.
AB  - The (1)H and (13)C NMR signal assignment of the data of 13 scopadulane-type
      diterpenes is reported. It was based on one- and two- dimensional NMR techniques
      which included (1)H, (13)C, DEPT, HMQC and 1D NOE difference spectroscopy.

PMID- 16106477
TI  - Onset of antidepressant action: a pharmacological question?
AB  - OBJECTIVE: This study was conducted to analyse the onset of action of
      antidepressants in naturalistic conditions. METHOD: Multicenter, prospective,
      open-label, non-comparative naturalistic study among 582 depressed outpatients
      treated with mirtazapine. The patients were assessed at screening, and after 1, 2
      and 4 weeks by the 17-item Hamilton depression rating scale (17-HAM-D) and
      clinical global impression (CGI). Onset of action was measured by traditional
      analyses based on the time to a persistent reduction of more than 50% from
      baseline on the 17-HAM-D. Patients were grouped into four groups: very fast
      responders, fast responders, traditional responders and partial or non
      responders. The non-parametric Kruskall-Wallis test was used to assess
      differences between the groups and logistic regression to predict response after
      1 week of treatment. RESULTS: 16% of patients had a very fast response, 42.1% a
      fast response, 26.5% a traditional response and 15.5% a partial or non-response.
      There were no significant differences between these groups with regard to dose of
      mirtazapine or sociodemographic characteristics. The baseline total 17-HAM-D was
      lower in the faster groups than in the slower groups. The evolution of 17-HAM-D
      items was similar in each responder group. CONCLUSION: Time to response varied
      from early faster response to late slower response. The evolution of 17-HAM-D for
      each type of response was similar, but occurred at a different time in each
      group.

PMID- 16106478
TI  - Assessment of sexual functioning in depressed patients treated with mirtazapine:
      a naturalistic 6-month study.
AB  - Antidepressant-induced sexual dysfunction is a frequent side effect which may
      greatly contribute to treatment non compliance. Mirtazapine has a pharmacological
      profile expected to result in a lack of sexual dysfunction. The main purpose of
      this 6-month open-label study was to evaluate the effects of mirtazapine on
      sexual function of a sample of depressed patients. METHODS: Seventy-eight
      patients meeting DSM-IV criteria for major depression or adjustment disorder with
      depressed mood or with mixed anxiety and depressed mood, sexually active prior to
      the episode, were treated with mirtazapine (15-60 mg/day). Effectiveness was
      assessed using the 17-item Hamilton rating scale for depression (HAM-D-17), the
      Hamilton rating scale for anxiety (HAM-A) and the clinical global impression
      (severity and improvement) scales (CGI). Sexual function was evaluated with the
      psychotropic-related sexual dysfunction questionnaire (PRSexDQ) which detects
      clinical changes in sexual dysfunction. RESULTS: Forty-eight patients (61.5%)
      were experiencing sexual dysfunction at baseline. A return to normal sexual
      functioning was observed in 27 of 38 (71.1%) patients completing the study.
      Significant reductions in mean total PRSexDQ scores were detected at day 90 and
      endpoint and only four patients withdrew or required dose reduction due to
      mirtazapine-induced sexual dysfunction. A total of 37 patients (47.4%) achieved
      complete remission of depression (HAM-D-17 score <or= 7) at endpoint. Only seven
      patients (9.0%) withdrew the study because of adverse events. CONCLUSION:
      Mirtazapine showed in this study that it is an effective and well-tolerated
      antidepressant treatment with a possibly lower incidence of sexual side effects
      than other antidepressants.

PMID- 16106479
TI  - Meta-analysis of sentinel node imprint cytology in breast cancer.
AB  - BACKGROUND: Intraoperative diagnosis of breast cancer metastases in axillary
      sentinel nodes is desirable to avoid a second operation for lymphadenectomy.
      Imprint or touch-preparation cytology is a popular technique that has high
      specificity and a wide range of sensitivity. METHODS: A systematic search of
      electronic databases was performed. Included articles were assessed for
      methodological and reporting quality. Random-effects model pooled estimates of
      sensitivity and specificity were calculated. Single-variable and multivariable
      meta-regression analyses were performed for predictors of sensitivity. RESULTS:
      Thirty-one studies were included; all were of good methodological quality but
      reporting quality varied. Pooled sensitivity of imprint cytology was 63 (95 per
      cent confidence interval (c.i.) 57 to 69) per cent and specificity was 99 (95 per
      cent c.i. 98 to 99) per cent. Pooled sensitivity for macrometastases was 81 per
      cent and that for micrometastases 22 per cent. Mean or median primary tumour size
      (P = 0.004), the prevalence of metastases (P = 0.103) and the proportion of
      micrometastases (P = 0.022) were significant risk factors in single-variable meta
      regression analysis. Only the proportion of micrometastases remained significant
      in multivariable analysis. Frozen sectioning had better sensitivity than imprint
      cytology in three of four direct comparisons. CONCLUSION: Imprint cytology is
      simple and rapid, and has good sensitivity for macrometastases. The significance
      of poor sensitivity for micrometastases will be determined by trials
      investigating their natural history.

PMID- 16106480
TI  - Randomized clinical trial comparing 5-year recurrence rate after laparoscopic
      versus Shouldice repair of primary inguinal hernia.
AB  - BACKGROUND: The Shouldice technique is the 'gold standard' of open non-mesh
      hernia repair. The aim of this study was to compare 5-year recurrence rates after
      Shouldice and laparoscopic transabdominal preperitoneal patch (TAPP) repair for
      primary inguinal hernia. METHOD: Men with a primary unilateral inguinal hernia
      were randomized to either Shouldice or TAPP operation. An independent observer
      scored the surgeons' performance. Follow-up comprised clinical examination after
      1 year, a questionnaire after 2 and 3 years, and a clinical examination after 5
      years. RESULTS: Between February 1993 and March 1996, 1183 patients were
      included. Nine hundred and twenty patients were followed for 5 years, 454 in the
      TAPP group and 466 in the Shouldice group. Recurrences were evenly distributed
      between groups throughout the follow-up period. The cumulative recurrence rate
      after 5 years was 6.6 per cent in the TAPP group and 6.7 per cent in the
      Shouldice group. Postoperative pain was a risk factor for recurrence after
      Shouldice operation but not after TAPP repair. There was a correlation between a
      low surgeon's performance score and recurrence. CONCLUSION: The 5-year recurrence
      rate is acceptable, with no difference between TAPP and Shouldice repair. Poor
      operative performance resulted in a higher recurrence rate. The TAPP operation
      represents an excellent alternative for primary inguinal hernia repair.

PMID- 16106481
TI  - Diagnostic peritoneal lavage--an obituary (Br J Surg 2005; 92: 517-518).

PMID- 16106482
TI  - Validity of the Glasgow Aneurysm Score and the Hardman Index in predicting
      outcome after ruptured abdominal aortic aneurysm repair (Br J Surg 2005; 92: 570
      573).

PMID- 16106483
TI  - Validity of the Glasgow Aneurysm Score and the Hardman Index in predicting
      outcome after ruptured abdominal aortic aneurysm repair (Br J Surg 2005; 92: 570
      573).

PMID- 16106484
TI  - Randomized trial of traditional dissection with electrocautery versus ultrasonic
      fundus-first dissection in patients undergoing laparoscopic cholecystectomy (Br J
      Surg 2005; 92: 810-813).

PMID- 16106485
TI  - Caffeine at work.
AB  - RATIONALE: There is a large literature on the effects of caffeine on performance.
      Most of the studies have been conducted in the laboratory and further information
      is required on the effects of caffeine consumption on performance and safety at
      work. OBJECTIVES: The present studies aimed to determine whether the level of
      caffeine consumption influenced changes in alertness and performance over the
      working day. Secondary analyses of a large epidemiological database were also
      conducted to examine associations between caffeine consumption and cognitive
      failures and accidents at work. METHODS: In the first study 110 volunteers, all
      of whom were regular caffeine consumers, rated their alertness and carried out a
      simple reaction time task before and after work on a Monday and Friday. Caffeine
      consumption during the day was recorded and volunteers were sub-divided into low
      and high consumers on the basis of a median split (220 mg/day). The second study
      involved secondary analyses of a database formed by combining the Bristol Stress
      and Health at Work and Cardiff Health and Safety at Work studies. In the first
      analyses associations between caffeine consumption and frequency of cognitive
      failures were examined in a sample of 1253 white-collar workers. The second set
      of analyses examined associations between caffeine consumption and accidents at
      work in a sample of 1555 workers who were especially at risk of having an
      accident. RESULTS: The results from the first study showed that those who
      consumed higher levels of caffeine reported significantly greater increases in
      alertness over the working day and a significantly smaller slowing of reaction
      time. The results from the second study demonstrated significant associations
      between caffeine consumption and fewer cognitive failures and accidents at work.
      After controlling for possible confounding factors it was found that higher
      caffeine consumption was associated with about half the risk of frequent/very
      frequent cognitive failures and a similar reduction in risk for accidents at
      work. CONCLUSIONS: Overall, the results from the three analyses show that
      caffeine consumption may have benefits for performance and safety at work.

PMID- 16106486
TI  - Evaluation of a behavioural weight management programme for patients with severe
      mental illness: 3 year results.
AB  - Excess weight is a common problem in the general population and in those with
      severe mental illness and is associated with a range of adverse consequences. The
      evidence base for managing excess weight in those with severe psychiatric illness
      is small. We report the outcome of a weight management programme provided in a
      community mental health centre. The programme consisted of group sessions, held
      weekly and lasting one hour. Participants self-referred and attended as many
      sessions as they wished. Sessions included weighing, feedback from participants
      and education on a range of issues including healthy eating and exercise. Over a
      3-year period 70 patients, predominantly with schizophrenia, attended the
      programme. Length of follow-up ranged from 2 weeks to 3 years. Data for all 70
      patients was evaluated. The mean BMI at entry to the programme was 32.5 kg/m2.
      The mean number of sessions attended was 34. Patients achieved a mean weight loss
      of 4.97 kg. The mean BMI at last attendance was 30.7 kg/m2. Weight loss
      correlated with number of sessions attended (p = 0.0001). This study demonstrates
      the long-term value of a weight management programme at 3 years and supports the
      hypothesis that weight loss can be achieved using a simple behavioural
      intervention in motivated psychiatric patients.

PMID- 16106487
TI  - Psychotropic medication use and accidents, injuries and cognitive failures.
AB  - BACKGROUND: Psychotropic medication has the potential to impair psychomotor and
      cognitive function, and several medications have well documented links to
      increased accident and injury susceptibility. Those developed more recently have
      many fewer side effects. However, there is little work examining any association
      between psychotropic medication use and safety within the context of other
      demographic, health and lifestyle factors. AIMS: To examine and compare any
      associations between psychotropic medication use (including benzodiazepines,
      tricyclics and SSRIs) and accidents, injuries and cognitive failures in a
      community sample. METHODS: A postal questionnaire survey was conducted among
      people selected at random from the electoral registers of Cardiff and Merthyr
      Tydfil. RESULTS: Psychotropic medication use was associated with accidents,
      injuries and cognitive failures, particularly among those who already had higher
      levels of other risk factors and/or continuing mental health problems.
      CONCLUSIONS: The well established associations between accidents and injuries and
      older psychotropic medications were replicated. SSRIs, however, were relatively
      safer. The study also highlighted the need to consider any effect of psychotropic
      medication within the context of both mental health status and other factors.

PMID- 16106488
TI  - Differential effects of chronic lithium and valproate on brain activation in
      healthy volunteers.
AB  - RATIONALE: Previous functional imaging studies have shown altered brain activity
      during cognitive task performance in bipolar patients. However, the fact that
      these patients are often on medication makes it unclear to what extent these
      changes reflect treatment effects. OBJECTIVES: This study aims to identify
      regional brain activity changes occurring following lithium and valproate
      treatment in healthy volunteers. METHODS: This was a double-blind, placebo
      controlled, study in which volunteers received either 1000 mg sodium valproate (n
      = 12), 900 mg lithium (n = 9), or placebo (n = 12). Functional images were
      acquired using functional magnetic resonance imaging (fMRI) while subjects
      performed three cognitive tasks, a word generation paradigm, a spatial attention
      task and a working memory task. fMRI was carried out both before and after 14
      days of treatment with valproate, lithium or placebo. The changes in the
      magnitude of the blood-oxygen-level-dependent (BOLD) signal after treatment were
      compared between the groups using a one-way ANOVA for each task followed by a
      post-hoc multiple comparisons correction. RESULTS: A significant group effect was
      noted in the change in BOLD signal magnitude from baseline to post-treatment, in
      all three tasks (working memory p< 0.000; spatial attention task p = 0.003; word
      generation paradigm p = 0.030). In the working memory task, the lithium group had
      a significant decrease in BOLD signal change, compared with the control group (p<
      0.000). A decrease in BOLD signal change was also noted in the valproate group,
      in the spatial attention task (p = 0.004). Both lithium and valproate groups had
      a decreased BOLD signal in the verbal task, following treatment, compared with
      the placebo group (p = 0.061 (lithium approached significance); p = 0.050
      (valproate)). CONCLUSIONS: These findings suggest that lithium and valproate have
      independent effects on brain activation that vary in a task and region-dependent
      manner.

PMID- 16106489
TI  - Comparison of experimental nerve injury caused by ultrasonically activated
      scalpel and electrosurgery (Br J Surg 2005; 92: 772-777).

PMID- 16106491
TI  - Support-seeking, perceived support, and anxiety in mothers and fathers after
      children's cancer treatment.
AB  - The objective was to examine the relationships between anxiety, the seeking of
      social support as a coping strategy, and perceived social support among mothers
      (n=103) and fathers (n=81) of children with successfully completed treatment for
      cancer. Assessments were done using self-report instruments. The mediating effect
      of perceived support on the relationship between social support-seeking and
      anxiety was evaluated through path analysis, and comparisons were done in order
      to evaluate effects of gender. For mothers and fathers alike, a positive
      relationship of moderate strength between support-seeking and perceived support
      was found. Anxiety was negatively related to support-seeking (mothers r=-0.22,
      p=0.025; fathers r=-0.21, p=0.063) as well as perceived support (mothers r=-0.55,
      p<0.001; fathers r=-0.41, p<0.001), although the relationship for support-seeking
      was weak. The path analysis showed that perceived support only to a minor extent
      could strengthen this association. The significance of support-seeking and
      perceived support was stronger for mothers than for fathers, as regards their
      association with anxiety. However, the patterns of interrelations were similar
      for mothers and fathers. In conclusion, parents' subjectively perceived support
      appears to be more important for anxiety regulation than their support-seeking
      coping. In clinical practice, individual variation should be acknowledged, and
      presumptions of general gender differences avoided.

PMID- 16106492
TI  - The complex antigenicity of a small external region of the C-terminal tail of the
      HIV-1 gp41 envelope protein: a lesson in epitope analysis.
AB  - The newly discovered external tail loop within the C-terminal tail of the gp41
      transmembrane subunit of the HIV-1 envelope protein comprises approximately 40
      residues, and within this are 18-residues ((734)PDRPEGIEEEGGERDRDR(751)) that
      include three antibody-reactive regions. The antigenicity is complex, and changes
      according to the biological context of the gp41. It is thus of interest both to
      the HIV specialist and protein immunologists. The antibody-reactive region,
      centred on the sequence ERDRD, encompasses three distinct epitopes which are
      expressed in different combinations on infected cells, wt virions, prefusion
      virion-cell complexes, and a neutralising antibody escape mutant virion. In
      addition ERDRD-specific antibodies have one or more antiviral activities, and
      variously neutralise the infectivity of free virions, neutralise virions already
      attached to the target cell, reduce the production of infectious progeny, and
      inhibit the ability of infected cells to fuse with non-infected cells. Antibodies
      to PDRPEG and IEEE have no apparent antiviral activity even though the footprints
      of the IEEE- and ERDRD-specific antibodies overlap. This review marshals the
      available experimental data with the aim of understanding the significance of the
      gp41 tail loop to the HIV-1 life cycle, and its relevance to potential anti-viral
      measures. There are lessons here, too, that are relevant to the comprehension of
      the antigenicity of short protein segments in general.

PMID- 16106493
TI  - Identification of risk factors for the development of complications following
      extended and superextended lymphadenectomies for gastric cancer.
AB  - BACKGROUND: Extended lymphadenectomy for gastric carcinoma has been associated
      with high mortality and morbidity rates in several multicentre randomized trials.
      METHODS: Using data from 523 patients registered for a prospective randomized
      trial comparing extended (D2) and superextended (D3) lymphadenectomies, risk
      factors for overall complications and major surgical complications (anastomotic
      leakage, intra-abdominal abscess and pancreatic fistula) were identified by
      multivariate logistic regression analysis. RESULTS: Mortality and morbidity rates
      were 0.8 per cent (four of 523) and 24.5 per cent (128 of 523) respectively.
      Pancreatectomy (relative risk 5.62 (95 per cent confidence interval (c.i.) 1.94
      to 16.27)) and prolonged operating time (relative risk 2.65 (95 per cent
      confidence interval 1.34 to 5.23)) were the most important risk factors for
      overall complications. A body mass index of 25 kg/m2 or above, pancreatectomy and
      age greater than 65 years were significant predictors of major surgical
      complications. CONCLUSION: Pancreatectomy should be reserved for patients with
      stage T4 disease. Age and obesity should be considered when planning surgery.

PMID- 16106494
TI  - Is symptomatology useful in distinguishing between carpal tunnel syndrome and
      cervical spondylosis?
AB  - Hand paraesthesia is a common symptom found in patients either with carpal tunnel
      syndrome or cervical spondylosis. To differentiate between the two conditions, it
      is important to identify additional diagnostic symptoms. Ninety-two patients with
      operated carpal tunnel syndrome and 138 patients with spinal surgery for cervical
      spondylosis were reviewed. After exclusion of cases co-morbid with both cervical
      spondylosis and carpal tunnel syndrome or other neurological disorders, 44
      patients with carpal tunnel syndrome and 41 patients with cervical spondylosis
      were compared. There were significant differences in the symptomatology between
      the two groups. In carpal tunnel syndrome, 84% had nocturnal paraesthesia, 82%
      hand paraesthesia were aggravated by hand activity, and hand pain occurred in
      64%. The incidences were only 10%, 7% and 10%, respectively in cervical
      spondylosis. Neck pain was present in 76% of cervical spondylosis but only in 14%
      of carpal tunnel syndrome, and lower limb symptoms were present in 44% of
      cervical spondylosis and only 9% in carpal tunnel syndrome.

PMID- 16106495
TI  - Gradual nerve elongation affects nerve cell bodies and neuro-muscular junctions.
AB  - The purpose of this study is to clarify the reactions of the neuro-muscular
      junction and nerve cell body to gradual nerve elongation. The sciatic nerves of
      Japanese white rabbits were lengthened by 30 mm in increments of 0.8 mm/day, 2.0
      mm/day and 4.0 mm/day. A scanning electron microscopic examination showed no
      degenerative change at the neuro-muscular junction, even eight weeks after
      elongation in the 4-mm group. Hence, neuro-muscular junction is not critical for
      predicting damage from gradual nerve elongation. There were no axon reaction
      cells in the 0.8-mm group, a small amount in the 2-mm group, and a large amount
      in the 4-mm group. The rate of growth associated protein-43 positive nerve cells
      was significant in the 4-mm group. Hence, the safe speed for nerve cells appeared
      to be 0.8-mm/day, critical speed to be 2.0-mm/day, and dangerous speed to be 4.0
      mm/day in this elongation model.

PMID- 16106496
TI  - The effects of forearm rotation on three wrist measurements: radial inclination,
      radial height and palmar tilt.
AB  - The purpose of this study was to evaluate and quantify the effects of forearm
      rotation on radial inclination, radial height and palmar tilt. Seventeen arms,
      nine cadaveric and eight volunteer, were examined using a radiolucent device that
      allowed for the controlled rotation of each arm. Lateral and posterior-anterior X
      rays were taken at 5 degrees increments which were then measured by two
      physicians using standardised protocol. The results revealed that all three
      measurements were significantly affected by forearm rotation with forearm
      supination increasing the apparent measurements and forearm pronation decreasing
      the apparent measurements. This relationship was well characterised by linear
      trend modelling such that forearm pronation of 10 degrees decreased the apparent
      radial inclination, radial height and palmar tilt by 2.8 degrees , 1.6 mm and 4.4
      degrees , respectively. This study demonstrates that forearm rotation is an
      important factor in the accurate evaluation of wrist measurements, and that
      slight rotation of the wrist during radiographic imaging may significantly alter
      management decisions given established surgical criteria.

PMID- 16106497
TI  - Ulnocarpal impaction syndrome restricts even midcarpal range of motion.
AB  - Ulnocarpal impaction syndrome is believed to be caused by abutment between the
      ulna and the ulnar carpus. We measured radiocarpal and midcarpal ranges of motion
      in 40 patients with ulnocarpal impaction syndrome by radiographic motion studies.
      The results showed that the radiocarpal and midcarpal ranges of motion were
      equally restricted in the affected wrist compared with the unaffected wrist.
      Therefore, motion of the radiocarpal joint and midcarpal joint contributed
      equally to total wrist motion bilaterally. No correlation between ulnar variance
      and the contribution of radiocarpal motion to overall wrist motion was found.
      Restriction of wrist motion in ulnocarpal impaction syndrome is not caused
      directly by abutment between the ulna and ulnar carpus, but a satisfactory
      explanation for restricted motion is still lacking.

PMID- 16106498
TI  - Carpal tunnel release with a limited palmar incision: clinical results and pillar
      pain at 18 months follow-up.
AB  - Limited open carpal tunnel release was performed in 58 hands (44 patients) using
      a single 1.5 cm palmar incision according to the technique described by Lee and
      Strickland. The patients were assessed at regular intervals after surgery for
      hand functions and subjective symptoms, in particular pillar pain. There was
      rapid wound recovery with minimal post-operative pain and scarring, and return to
      functional activities within four weeks. At an average follow-up of 18 months
      (range 14-24 months), 91% of patients had complete or significant resolution of
      hand paraesthesia. No patient required further surgery. However, pillar pain was
      found in 48% of hands at four weeks, 21% at 12 weeks, 12% at six months, 9% at 12
      months and 7% at the last follow-up. The significance of the incidence of pillar
      pain is discussed.

PMID- 16106499
TI  - Intrasheath triamcinolone injection for the treatment of trigger digits in adult.
AB  - The purpose of this study is to describe our technique of intrasheath
      triamcinolone injection for trigger digit and to evaluate the treatment outcome.
      Seventy-two patients of 81 digits treated with intrasheath triamcinolone
      injection were followed up for at least one year and interviewed in our clinic.
      The injection was performed in all patients by one of the authors at two-week
      intervals. The amount used was 1 ml (10 mg) of triamcinolone and was mixed with 1
      ml of 1% lidocaine and tried precise injection into the tendon sheath. According
      to the evaluation method developed by Patel and Moradia, they were excellent in
      67 digits, good in ten digits, fair in three digits, and poor in one digit.
      Satisfactory results were obtained in 95% of the digits, and the effectiveness
      rate was higher than previously reported. But it should also be noted that
      triamcinolone easily induces local side effects such as dermatitis.

PMID- 16106500
TI  - Classification of benign fatty tumours of the upper limb.
AB  - In this paper, the authors offer a classification of benign fatty tumours of the
      upper limb. There are three histologically distinct types of fat cells: immature
      fat cells which give rise to lipoblastomas, mature brown fat cells which give
      rise to hibernomas and mature white fat cells which give rise to lipomas. Lipomas
      are the most common and they are sub-classified according to the anatomic site of
      fat cells into dermal, subcutaneous and sub-fascial lipomas; or tumours directly
      related to muscle, bone, synovium or nerve. Finally, the authors review 67
      patients with benign fatty tumours of the upper limb and provide clinical
      examples of these tumours including their characteristic histological and
      radiological features.

PMID- 16106501
TI  - Ideas and innovations: radial approach to carpal tunnel release in conjunction
      with thumb carpometacarpal arthroplasty.
AB  - Several authors have written about the co-existence of thumb carpometacarpal
      arthritis and carpal tunnel syndrome, and 4% to 43% of patients undergoing thumb
      carpometacarpal arthroplasty also have a carpal tunnel release. Some authors
      advocate that carpal tunnel release and thumb carpometacarpal arthroplasty should
      be performed at the same time. We perform a combined thumb carpometacarpal
      arthroplasty and radial approach carpal tunnel release through a single incision.
      The purposes of this study are to (1) determine the safety of this approach and
      (2) evaluate the effectiveness of this approach in decreasing the pain and
      numbness observed prior to surgery. Eight patients had combined thumb
      carpometacarpal arthroplasty and radial approach carpal tunnel release. With an
      average follow up of 14 weeks, all patients reported an improvement in pain and
      numbness. No nerve injuries occurred, and no difficulty in wrist flexion was
      observed. One patient had pillar pain persisting at 19 weeks follow-up. One
      patient had basilar thumb pain at 19 weeks, though this was improved over pre
      operative levels.

PMID- 16106502
TI  - Prevalence of carpal tunnel syndrome in workers from a fishnet factory in
      Thailand.
AB  - We determined the prevalence of carpal tunnel syndrome (CTS) at a fishnet factory
      in order to discern the possible associated risk factors at this type of
      workplace. The 662 workers were interviewed then physically examined. The
      prevalence of CTS was 14.5%, which is significantly higher than in the general
      population. Workers directly involved in the production of fishnets had a
      significantly higher risk of CTS than the factory's office workers or housemaids
      (odds ratio = 1.84; range, 1.03-3.29; 95% CI, p = 0.049). There was no
      association between the length of employment in the factory with CTS (odds ratio
      = 1.13; range, 0.77-1.66; 95% CI, p = 0.591). Our results confirm that factory
      jobs with repetitive hyperflexing and twisting of the wrists are at risk of CTS.

PMID- 16106503
TI  - Palmar plating for AO/ASIF C3.2 fractures of the distal radius with
      arthroscopically assisted reduction.
AB  - We performed a retrospective study of 15 patients with AO/ASIF C3.2 fracture of
      the distal radius. All patients were treated with arthroscopically assisted
      reduction of the radiocarpal joint followed by palmar plating with autologous
      bone graft, with a follow-up evaluation of 24 months. According to the demerit
      point system of Gartland and Werley, five patients had excellent results and 10
      had good results. Grade 1 arthritic changes were found in 10 patients even though
      with no step-off on radiographs. In the current study, this combined treatment
      was challenging and useful for AO/ASIF C3.2 fractures.

PMID- 16106504
TI  - A long-term follow-up of silicone-rubber interposition arthroplasty for
      osteoarthritis of the thumb carpometacarpal joint.
AB  - There are several surgical options for osteoarthritis (OA) of the thumb
      carpometacarpal (CMC) joint. This paper presents our long-term clinical and
      radiographic review of 12 thumbs in ten patients treated by partial trapezial
      excision and silicone-rubber interposition arthroplasty. The follow-up period
      averaged 15; three years with a ten-year minimum. Although the procedure provided
      early pain relief in most thumbs, all but two had mild to severe pain at follow
      up. The average range of post-operative palmar abduction was 23 degrees. The
      average post-operative grip strength was 9.5 kg. Both tip and key pinch between
      thumb and index finger averaged about 50% that of normal subjects. Dislocation of
      the implant occurred in two joints and breakages in five. Bony erosions around
      the implant, which we attributed silicone synovitis, were found in four thumbs.
      The indications for silicone-rubber interposition arthroplasty for OA of the
      thumb CMC joint should be severely restricted as these produced unsatisfactory
      long-term results.

PMID- 16106505
TI  - Comparison of the surgical outcomes for trigger finger and trigger thumb:
      preliminary results.
AB  - We reviewed 110 trigger digits, treated surgically, to compare the outcomes of
      trigger finger and trigger thumb in terms of peri-operative characteristics and
      complications. The patients with trigger thumb complained mainly of pain on
      motion, while those with trigger finger complained of triggering or limited range
      of motion. Trigger fingers had a significantly longer duration before surgery
      than did trigger thumbs. Trigger fingers took significantly longer for the
      symptoms to subside. In our series, 64% of trigger fingers had a flexion
      contracture of the PIP joint more than three weeks after surgery. Our results
      suggest that the peri-operative characteristics and outcomes differ between
      trigger finger and thumb, and that the surgical outcome for trigger finger was
      poorer than that for trigger thumb, partly due to flexion contracture of the PIP
      joint.

PMID- 16106506
TI  - Ulnar dislocation of fifth carpometacarpal joint.
AB  - Carpometacarpal dislocations may be dorsal, volar or divergent type but most are
      dorsal with involvement of 4th and 5th metacarpal. We are reporting first case of
      ulnar type of unilateral dislocation of 5th carpometacarpal joint.

PMID- 16106507
TI  - Avascular necrosis of the triquetrum: a case report.
AB  - A case of total ischemia of the triquetrum after a crushing injury to the right
      wrist by a dumbbell is reported. He was treated conservatively with splinting and
      analgesia. There was complete clinical and radiological recovery after a follow
      up of one year.

PMID- 16106508
TI  - Use of a hollow needle for drilling holes in small bones to guide intraosseous
      wires.
AB  - Holes are frequently drilled across small bones to achieve fixation with
      intraosseous wires. We describe an effective, simple and cheap alternative to the
      use of K-wires for this purpose in this article.

PMID- 16106509
TI  - Giant cell tumour of tendon sheath in a child: a case report.
AB  - Giant cell tumour of the tendon sheath is uncommon in children. We describe this
      tumour arising from the right ring finger in an eight-year-old girl. Plane
      radiographs showed a soft tissue mass with erosion of the distal phalanx. The
      tumour was treated by surgical excision with good outcome.

PMID- 16106510
TI  - Pisiform and hamate coalition: case report and review of literature.
AB  - Pisiform and hamate coalition is a rare anomaly of the carpal bones; a
      symptomatic case is an especially rare condition. We report a case of symptomatic
      pisiform and hamate coalition in a 15-year-old Japanese male. The literature of
      pisiform and hamate coalition is reviewed.

PMID- 16106511
TI  - Trigger finger caused by an old partial flexor tendon laceration: a case report.
AB  - We report a rare case of trigger finger caused by an old partial laceration of
      the flexor digitorum superficialis. The triggering occurred five months after
      injury. This case was the latest presentation of triggering in the literature.
      The patient was managed by incising the A1 pulley and suturing the flexor tendon
      flap after trimming. He was relieved of triggering and there was no recurrence.

PMID- 16106512
TI  - Rupture of the flexor digitorum profundus tendon to the small finger within the
      carpal tunnel.
AB  - We report three patients who sustained a rupture of the flexor digitorum
      profundus tendon to the small finger within the carpal tunnel. There was a common
      mechanism of injury, each rupture occurred during resisted flexion of the digit
      with the metacarpophalangeal joint in extension. All the patients were male, one
      patient had an asymptomatic undiagnosed fracture of the hook of hamate, one
      patient had radiological evidence of piso-triquetral osteoarthritis. In each
      case, an attrition rupture was confirmed at surgery.

PMID- 16106513
TI  - Aseptic necrosis of the hamate: a case report.
AB  - The case of a 25-year-old man with osteonecrosis of the hamate is reported. He
      had pain and swelling in his right wrist. The diagnosis was accomplished with
      plain radiographs as well as with MRI. The case was treated surgically that
      included resection of the necrotic bone. The occured cavity was filled with
      autogenous cancellous bone graft. In addition, capito-hamate arthrodesis was
      performed. Histopathological examination following the operation demonstrated
      avascular necrosis of the hamate. The arthrodesis was obtained four months after
      the operation.

PMID- 16106514
TI  - An improvised depth gauge using a hypodermic needle.
AB  - A simple solution to the problem of a broken depth gauge is suggested. A
      hypodermic needle is bent to simulate the shape of a depth gauge and used in a
      similar way. This allows measurement of the screw length against the scale on the
      set. We would advocate this method only when there is no suitable alternative
      depth gauge available.

PMID- 16106515
TI  - T-condylar fracture of the distal humerus in a three-year-old child.
AB  - A three-year-old girl suffered a T-condylar fracture of the distal humerus. Open
      reduction and pinning were performed. Three years after injury, there was no
      functional disturbance or radiographic evidence of avascular necrosis or
      epiphyseal growth arrest.

PMID- 16106516
TI  - Congenital metacarpal synostosis treated by double bone blocks technique: a case
      report from Thailand.
AB  - Congenital metacarpal synostosis is a rare congenital anomaly in the hand,
      especially in our area. There were several reports of surgical techniques for
      correction deformities. We report this rare condition in our hospital and
      treatment with the metacarpal osteotomy and double bone blocks technique of
      grafting.

PMID- 16106517
TI  - Report of an unusual case of trigger finger secondary to phalangeal exostosis.
AB  - Trigger finger is commonly secondary to stenosing tenosynovitis. Space occupying
      lesions in the tendon bed, although uncommon, may prevent smooth tendon gliding.
      These include lipoma, anomalous muscle insertions, tumours of the tendon sheath
      and haemangiomas. We describe a patient who had triggering of the left middle
      finger at the proximal interphalangeal joint due to an exostosis blocking the
      flexor tendons gliding. Removal of the exostosis relieved the problem. The
      clinician must be aware that there are other causes for triggering. These may be
      identified with pertinent findings in the history and physical examination.

PMID- 16106518
TI  - Historical case: Aenictinae: the arthropodic suture.

PMID- 16106519
TI  - Using ethics to fight bioterrorism.

PMID- 16106520
TI  - Using ethics to fight bioterrorism.

PMID- 16106521
TI  - Using ethics to fight bioterrorism.

PMID- 16106522
TI  - Using ethics to fight bioterrorism.

PMID- 16106523
TI  - Using ethics to fight bioterrorism.

PMID- 16106524
TI  - KR-62436, 6-{2-[2-(5-cyano-4,5-dihydropyrazol-1-yl)-2
      oxoethylamino]ethylamino}nicotinonitrile, is a novel dipeptidyl peptidase-IV (DPP
      IV) inhibitor with anti-hyperglycemic activity.
AB  - Dipeptidyl peptidase-IV (DPP-IV) is involved in the inactivation of glucagon-like
      peptide-1 (GLP-1), a potent insulinotropic peptide. Thus, DPP-IV inhibition can
      be an effective approach to treat type 2 diabetes mellitus by potentiating
      insulin secretion. This study describes the biological effects of a new DPP-IV
      inhibitor, KR-62436 (6-{2-[2-(5-cyano-4,5-dihydropyrazol-1-yl)-2
      oxoethylamino]ethylamino}nicotinonitrile) in vitro and in vivo. KR-62436
      inhibited rat plasma DPP-IV, porcine kidney DPP-IV as well as human DPP-IV (Caco
      2) with IC50 values of 0.78, 0.49, 0.14 microM, respectively. In addition, the
      compound (10 microM) almost completely inhibited DPP-IV-mediated degradation of
      GLP-1 in vitro. KR-62436 inhibited the enzyme in a competitive manner, and
      exhibited selectivity against several proteases including proline-specific
      proteases. In vivo efficacy of the compound was examined by using normal C57BL/6J
      mice and ob/ob mice, a type 2 diabetes animal model. Administration of KR-62436
      to C57BL/6J mice either orally or subcutaneously resulted in the suppression of
      plasma DPP-IV activity, increase in intact GLP-1 and insulin levels in plasma.
      Furthermore, the plasma glucose concentrations during oral glucose tolerance test
      (OGTT) were reduced upon oral administration of KR-62436. This study demonstrates
      that KR-62436 could be a good lead compound for further development as a new anti
      diabetic agent.

PMID- 16106526
TI  - Bibliography. Current world literature. Facial plastic surgery.

PMID- 16106525
TI  - Addressing the limitations of structured abstracts.

PMID- 16106527
TI  - Biozzi mice: of mice and human neurological diseases.
AB  - In 1972 Guido Biozzi selectively bred mice to study the immunopathological
      mechanisms underlying polygenic diseases. One line, the Biozzi antibody high
      (AB/H) mouse (now designated the ABH strain) was later found to be highly
      susceptible to many experimentally induced diseases such as autoimmune
      encephalomyelitis, autoimmune neuritis, autoimmune uveitis, as well as virus
      induced demyelination and has thus been a key mouse strain to study human
      inflammatory neurological diseases. In this paper we discuss the background of
      the Biozzi ABH mouse and review how studies with these mice have shed light on
      the pathogenic mechanisms operating in chronic neurological disease.

PMID- 16106528
TI  - A motor function measure for neuromuscular diseases. Construction and validation
      study.
AB  - A new scale for motor function measurement has been developed for neuromuscular
      diseases. The validation study included 303 patients, aged 6-62 years. Seventy
      two patients had Duchenne muscular dystrophy, 32 Becker muscular dystrophy, 30
      limb-girdle muscular dystrophy, 39 facio-scapulo-humeral dystrophy, 29 myotonic
      dystrophy, 21 congenital myopathy, 10 congenital muscular dystrophy, 35 spinal
      muscular atrophy and 35 hereditary neuropathy. The scale comprised 32 items, in
      three dimensions: standing position and transfers, axial and proximal motor
      function, distal motor function. Agreement coefficients for inter-rater
      reliability were excellent (kappa=0.81-0.94) for nine items, good (kappa=0.61
      0.80) for 20 items and moderate (kappa=0.51-0.60) for three items. High
      correlations were found between the total score and other scores: Vignos (r=0.91)
      and Brooke (r=0.85) grades, Functional Independence Measure (r=0.91), the global
      severity of disability evaluated with visual analog scales by physicians (r=0.88)
      and physiotherapists (r=0.91). This scale is reliable, does not require any
      special equipment and is well-accepted by patients. Its sensitivity to change is
      being assessed to permit its use in clinical trials of neuromuscular diseases.

PMID- 16106529
TI  - The criteria for malleus removal in ossicular chain reconstruction.

PMID- 16106530
TI  - Acting Governor Codey signs Alternative to Discipline Bill into law.

PMID- 16106531
TI  - John Maynard Smith and recombination.

PMID- 16106532
TI  - John Maynard Smith and evolutionary game theory.

PMID- 16106533
TI  - Asymmetric population games and the legacy of Maynard Smith: From evolution to
      game theory and back?

PMID- 16106534
TI  - Fifty important papers in the history of muscle contraction and myosin motility.

PMID- 16106535
TI  - Seniors want Medicare savings accounts, early enrollment.

PMID- 16106536
TI  - Feridex-labeled mesenchymal stem cells: cellular differentiation and MR
      assessment in a canine myocardial infarction model.

PMID- 16106537
TI  - Subchronic toxicity of the gadolinium chelates.

PMID- 16106538
TI  - Molecular imaging of human thrombus with computed tomography.

PMID- 16106539
TI  - Drug delivery by angiographic contrast media: inhibition of restenosis.

PMID- 16106540
TI  - Detection of liver metastases from gastrointestinal cancer: comparision of high
      resolution MnDPDP enhanced MRI and FDG-PET.

PMID- 16106541
TI  - Oral manganese for liver and bile imaging.

PMID- 16106542
TI  - Gadobenate dimeglumine (MultiHance) in MR imaging of the CNS: studies to assess
      the benefits of a high relaxivity contrast agent.
AB  - The use of Gd-BOPTA as a contrast agent for morphological and functional MR
      imaging allows improved detection and delineation of CNS lesions compared to
      conventional gadolinium agents. This results not only to more confident
      diagnosis, but also to a substantially improved differential diagnosis process.
      The higher relaxivity of Gd-BOPTA also helps to optimize functional MR imaging
      studies e.g. perfusion MRI and dynamic MR angiographic protocols.

PMID- 16106543
TI  - Assessment of microvascular perfusion changes in a rat breast tumor model using
      SonoVue to monitor the effects of different anti-angiogenic therapies.

PMID- 16106544
TI  - Technical and practical considerations for permeability modeling of dynamic
      contrast enhanced MRI.

PMID- 16106545
TI  - [Enlarging one's professional horizons].

PMID- 16106546
TI  - Medicare drug benefit may do more harm than good.

PMID- 16106547
TI  - HIV disclosure and risk reduction research: practical implications.

PMID- 16106548
TI  - Eliciting risk narratives to explore ambivalence about disclosure.

PMID- 16106549
TI  - Coverage changes are coming: get the facts now.

PMID- 16106550
TI  - News from the 12th annual CROI.

PMID- 16106551
TI  - Introducing the linkages to care program.

PMID- 16106552
TI  - Healthy choices. Creating from nothingness.

PMID- 16106553
TI  - Healthy choices. Meditation techniques.

PMID- 16106554
TI  - Dropping acid: antacids and HIV medications.

PMID- 16106555
TI  - Testing positive: to panic, or not to panic?

PMID- 16106556
TI  - Metabolic disturbances in the absence of HAART.

PMID- 16106557
TI  - [Research on slit lamp bio-microscope image analysis system].
AB  - Slit lamp bio-microscope image analysis system can provide objective and
      quantitative diagnosis evidences for ophthalmologists and make available
      efficient storing, management and intercourse of sufferer information and
      diagnosis results. In this paper, the system is discussed on its devices,
      software structure, analysis process and algorithm.

PMID- 16106558
TI  - [Fetal/maternal multi-parameter monitor].
AB  - A fetal/maternal multi-parameter monitor is introduced here in the paper. It can
      monitor the vital signs of a fetus and his/her mother in a same screen
      synchronously. It is more useful in obstetric clinics. Its other functions
      include management of patient file, computer-assistant analyses.

PMID- 16106559
TI  - Identification and differentiation of Staphylococcus carnosus and Staphylococcus
      simulans by species-specific PCR assays of sodA genes.
AB  - The aim of this study was to design species-specific PCR assays for rapid and
      reliable identification and differentiation of Staphylococcus (S.) carnosus and
      S. simulans strains. Two different sets of primers, targeting the manganese
      dependent superoxide dismutase (sodA) gene of S. carnosus and S. simulans,
      respectively, were designed. Species-specificity of both sets of primers was
      evaluated by using 93 strains, representing 26 different species of the genus
      Staphylococcus, 3 species of the genus Kocuria (K.), 1 species of the genus
      Micrococcus (Mic.) and 1 species of the genus Macrococcus (Mac.) as reference. By
      using primers simF and simR the expected PCR fragment was obtained only when
      purified DNA from S. simulans strains was used. Amplification performed by using
      primers carF and carR produced a PCR fragment of the expected length, when DNA
      from strains of S. carnosus and S. condimenti were used as template.
      Nevertheless, DraI digestion of the carF/carR PCR fragment allowed a clear
      differentiation of strains of these two species. Species-specific PCR assays
      designed during this study, overcoming many of the limitations of the traditional
      identification procedures, can be considered a valid strategy for detection and
      identification of S. carnosus and S. simulans strains. The rapidity (about 4h
      from DNA isolation to results), the reliability and low cost of the PCR
      procedures established suggests that the methods may be profitably applied for
      specific detection and identification of S. carnosus, S. condimenti and S.
      simulans strains in starter cultures and meat products.

PMID- 16106560
TI  - Torsional stability of cross-link configurations: a biomechanical analysis.
AB  - BACKGROUND CONTEXT: Cross-link systems have been used to augment segmental spinal
      instrumentation since the earliest introduction of these fixation systems.
      Although transverse cross-links have little impact on sagittal motion of spinal
      constructs, cross-linkage does affect torsional rigidity. Despite the wide
      variety of cross-link designs, almost all have been configured as transverse
      devices. The relative mechanical benefit of different cross-link configurations
      is not known. PURPOSE: The purpose of this study was to compare the torsional
      stability of three different cross-link configurations. STUDY DESIGN:
      Biomechanical analysis of segmental instrumentation constructs using porcine
      spines. METHODS: Thoracic porcine spines (T4 to T10) were instrumented with 6.5
      mm conical pedicle screws and 7.0-mm connecting rods from T5 to T9. Terminal
      vertebrae were embedded in polymethylmethacrylate (PMMA) after a T7 corpectomy.
      Four cross-link configurations were tested in a randomized manner: Un-cross
      linked Control (CONT); Transverse Rod-Rod (RR); Transverse Screw-Screw (SS); and
      Diagonal Screw-Screw (DX) Cross-links. The specimens were rotated to 3 Nm at a
      rate of 0.2 degrees/s and cycled six times with data acquisition over the final
      two cycles. Stiffness, rotation, and energy data were normalized to each control.
      A Newman-Keuls repeated measures analysis of variance was used to infer
      significant differences. RESULTS: Diagonal cross-link configurations provided the
      most rigid construct. Transverse cross-links did not significantly change
      torsional behavior compared with the unlinked control. Rotation and energy
      expended were not significantly greater torsional stiffness compared with other
      constructs tested (p<.01). CONCLUSIONS: The diagonal cross-link configuration
      provided increased torsional stiffness as compared with unlinked or transverse
      configurations. This observation should be considered in future cross-link
      designs.

PMID- 16106561
TI  - When an unusual lesion occurs in an odd place.

PMID- 16106562
TI  - From advanced imaging...when a broken pencil is more than just a broken pencil.

PMID- 16106563
TI  - ISEH 2005. Abstracts of the 34th Annual Meeting of the International Society for
      Experimental Hematology, Glasgow, Scotland, July 30-August 2, 2005.

PMID- 16106564
TI  - Abstracts of the 15th European Meeting on Hypertension, Milan, Italy, June 2005.

PMID- 16106565
TI  - Abstracts of the 1st Osteoarthritis Research Society Congress, Paris, France, 10
      12 December 1992.

PMID- 16106566
TI  - E = MC2: effective multicultural competence.

PMID- 16106567
TI  - Multiple choices for certification.

PMID- 16106568
TI  - Growth spurt for EDC recognition.

PMID- 16106569
TI  - On: Dogville: a parable on perversion.

PMID- 16106570
TI  - On: projective identification and consciousness alteration.

PMID- 16106571
TI  - On: a boycott by passport.

PMID- 16106572
TI  - Science-Based Solutions to Obesity: What are the Roles of Academia, Government,
      Industry, and Health Care? Proceedings of a symposium, Boston, Massachusetts,
      USA, March 10-11, 2004 and Anaheim, California, USA, October 2, 2004.

PMID- 16106574
TI  - Upon changing to a low bleed version of my column, some of the separations got
      worse. What happened? Is there anything I can do to restore the separations?

PMID- 16106573
TI  - [Recommendations of good practice: drug therapy for fibroma of uterus (October
      2004)].

PMID- 16106575
TI  - I have an analyte that exists in two conformational states in solution.
      Unfortunately, I have been trying to separate them but have not been successful.
      I am pretty sure that I should be able to separate them because I have seen a few
      examples where other investigators have separated conformers. Do you have any
      suggestions that I might try?

PMID- 16106576
TI  - Teaching teens by setting the scene.

PMID- 16106577
TI  - The illusion of common ground and mythical pluralism.

PMID- 16106578
TI  - [Management of wounds across Europe].

PMID- 16106579
TI  - Surgery in developing countries: essential training in residency.
AB  - HYPOTHESIS: A surgical elective in a developing country setting is an essential
      new component in academic residency training. DESIGN: A survey of residents and
      faculty within the Department of Surgery at the University of California-San
      Francisco, and a collaborative program piloted between the Department of Surgery
      at the University of California-San Francisco and Makerere University in Kampala,
      Uganda, including a 6-week clinical elective. SETTING: Mulago and Nsambya
      hospitals in Kampala, Uganda. PARTICIPANTS: Two residents and three faculty
      advisors at the University of California-San Francisco. INTERVENTION: Development
      of a 6-week pilot clinical surgical elective. MAIN OUTCOME MEASURES: Assessment
      of the level of interest in international health in an academic surgery program;
      pathology and case variety, diagnostic methods, and surgical and anesthetic
      resources and techniques in a pilot developing country. RESULTS: Forty percent of
      residents enter residency with prior international health experience whereas 90%
      express interest in a developing country elective. Twenty-five percent of faculty
      participate in voluntary international surgical service and research projects. As
      a result of the survey and the level of interest in our program, two visits to
      Uganda were made and a residency elective rotation was successfully created. This
      resulted in exposure of residents to the educational benefits of learning in a
      resource-constrained setting: a broader scope of surgical conditions and
      pathology, greater reliance on history-taking and physical examination skills in
      a low-technology environment, and sociocultural aspects of care provision.
      Greater questions about global health equity, access to information, and the role
      of surgery in public health are raised along with potential challenges in
      international collaboration. CONCLUSIONS: A developing country surgical
      experience complements the academic mission of service, training, and research,
      and should be an essential component of surgical training programs. There is
      interest among residents and faculty in such a program as well as a need for
      greater commitment to north-south collaborations among academic surgical
      institutions and societies, as has been successfully implemented abroad. More
      generally, surgery is an integral part of public health and health systems
      development worldwide.

PMID- 16106580
TI  - The time is now.

PMID- 16106581
TI  - BiDil raises questions about race as a marker.

PMID- 16106582
TI  - Neuroimaging heats up.

PMID- 16106583
TI  - Indian generics companies go on spending spree.

PMID- 16106584
TI  - Career path. David T. Wong.

PMID- 16106585
TI  - Therapeutic cancer vaccines.

PMID- 16106586
TI  - Rasagiline.

PMID- 16106587
TI  - [III--Relationship care at the family level. 2. Helping the family during family
      dynamic perturbations].

PMID- 16106588
TI  - Edgeworth approximation of multivariate differential entropy.
AB  - We develop the general, multivariate case of the Edgeworth approximation of
      differential entropy and show that it can be more accurate than the nearest
      neighbor method in the multivariate case and that it scales better with sample
      size. Furthermore, we introduce mutual information estimation as an application.

PMID- 16106589
TI  - Perfect fault tolerance of the n-k-n network.
AB  - It was shown in Phatak, Choi, and Koren (1993) that the neural network
      implementation of the n-k-n encoder-decoder has a minimal size of k = 2, and it
      was shown how to construct the network. A proof was given in Phatak and Koren
      (1995) that in order to achieve perfect fault tolerance by replicating the hidden
      layer, the required number of replications is at least three. In this note, exact
      lower bounds are derived for the number of replications as a function of n, for
      the n-2-n network and for the n- log2n-n network.

PMID- 16106590
TI  - On the slow convergence of EM and VBEM in low-noise linear models.
AB  - We analyze convergence of the expectation maximization (EM) and variational Bayes
      EM (VBEM) schemes for parameter estimation in noisy linear models. The analysis
      shows that both schemes are inefficient in the low-noise limit. The linear model
      with additive noise includes as special cases independent component analysis,
      probabilistic principal component analysis, factor analysis, and Kalman
      filtering. Hence, the results are relevant for many practical applications.

PMID- 16106591
TI  - Medicare program; inpatient rehabilitation facility prospective payment system
      for FY 2006. Final rule.
AB  - This final rule will update the prospective payment rates for inpatient
      rehabilitation facilities for Federal fiscal year 2006 as required under section
      1886(j)(3)(C) of the Social Security Act (the Act). Section 1886(j)(5) of the Act
      requires the Secretary to publish the classification and weighting factors for
      the inpatient rehabilitation facilities case-mix groups and a description of the
      methodology and data used in computing the prospective payment rates for that
      fiscal year. In addition, we are implementing new policies and are changing
      existing policies regarding the prospective payment system within the authority
      granted under section 1886(j) of the Act.

PMID- 16106592
TI  - Current awareness on yeast.

PMID- 16106593
TI  - Leflunomide: new indication. In psoriatic rheumatism: too many risks, too little
      efficacy.
AB  - (1) The severity of joint involvement in psoriatic rheumatism varies greatly and
      its outcome is difficult to predict; some patients have long-term spontaneous
      remissions. The best-evaluated slow-acting treatments are sulfasalazine and
      methotrexate; adding etanercept can help some patients who do not respond to
      these drugs. (2) Leflunomide, an immunosuppressant drug, is already marketed for
      the treatment of rheumatoid arthritis, a condition for which it shows a less
      favourable risk-benefit balance than methotrexate. (3) Leflunomide is now
      licensed in France for "active psoriatic rheumatism". (4) The only available
      clinical data come from a double-blind placebo-controlled trial in 190 patients.
      On the basis of a combined outcome measure, significantly more patients responded
      to leflunomide than to placebo (59% versus 29.7%). However, the patients' global
      assessment was less positive: 15.8% of patients felt their condition had
      deteriorated during leflunomide therapy, compared to 24.2% of patients in the
      placebo group. The study population was too heterogeneous to show which types of
      patients might benefit most from leflunomide therapy. (5) Pharmacovigilance
      studies have confirmed some severe adverse effects (hepatic, cutaneous and
      haematological) and have uncovered other previously unrecognised effects such as
      interstitial pneumonia, hypertension, weight loss, and peripheral neuropathies.
      (6) In France, leflunomide treatment costs nearly 10 times more than
      methotrexate. (7) We conclude that leflunomide should not be used to treat
      psoriatic rheumatism.

PMID- 16106594
TI  - Melagatran and ximelagatran: new drug. No real simplification of anticoagulant
      therapy.
AB  - (1) The reference drug for prophylaxis against venous thromboembolism after hip
      or knee replacement surgery is a low-molecular-weight heparin (LMWH), given
      subcutaneously for 1 to 5 weeks. Vitamin K antagonists, including warfarin, have
      similar risk-benefit balances. (2) Subcutaneous melagatran and its oral metabolic
      precursor ximelagatran have recently been granted marketing authorisation in
      France for use as prophylaxis after hip or knee replacement surgery. Melagatran,
      unlike LMWH, is a specific thrombin inhibitor. (3) There are four randomised
      double-blind trials in more than 9000 patients comparing these agents with a LMWH
      (enoxaparin in three trials, dalteparin in one). Melagatran was given
      subcutaneously for one or two days before being replaced with ximelagatran (as
      soon as oral feeding was possible) for 6 to 9 days. These trials showed no
      advantage of melagatran-ximelagatran in terms of clinical endpoints such as
      symptomatic deep venous thrombosis, pulmonary embolism, and death from all
      causes. (4) Three randomised double-blind trials have compared ximelagatran with
      warfarin in more than 5000 patients. Treatment lasted 7 to 12 days. Ximelagatran
      was no better than warfarin when assessed using clinical endpoints. (5) In these
      trials melagatran-ximelagatran did not increase the risk of bleeding compared
      with LMWH or warfarin. (6) Melagatran-ximelagatran can cause an increase in serum
      transaminase activity, and is contraindicated if pretreatment serum transaminase
      activity is more than twice the upper limit of normal. (7) Trials versus warfarin
      showed a higher risk of myocardial infarction in patients taking ximelagatran
      (0.7% versus 0.16%). (8) There are few data on the patient subgroups most likely
      to receive melagatran-ximelagatran, namely patients over 75, underweight and
      overweight patients, and patients with renal failure. (9) There is currently no
      clotting test that allows the melagatran-ximelagatran dose regimen to be adjusted
      in patients who have an increased risk of adverse effects due to overdosing.
      There is no available antidote if overdose occurs. (10) Erythromycin increases
      melagatran bioavailability, thereby increasing the bleeding risk. Melagatran and
      ximelagatran must not be combined with other anticoagulants, thrombolytic agents
      or antiplatelet drugs because of a increased bleeding risk. (11) In practice, low
      molecular-weight heparin remains the reference prophylactic treatment for venous
      thromboembolism after hip or knee replacement surgery.

PMID- 16106595
TI  - Pioglitazone, rosiglitazone, and rosiglitazone + metformin: new drugs. Glitazone
      + oral antidiabetic combination: inadequately evaluated.
AB  - (1) When single-agent therapy provides inadequate glycaemic control for patients
      with type 2 diabetes, most guidelines recommend metformin in combination with a
      glucose-lowering sulphonylurea as standard treatment, despite the lack of any
      proven impact on morbidity or mortality. Other options include switching to
      insulin or abandoning the target of strict glycaemic control. (2) Pioglitazone
      and rosiglitazone are approved for use in combination with a glucose-lowering
      sulphonylurea when metformin is poorly tolerated or contraindicated, and in
      combination with metformin in overweight patients. (3) A fixed-dose combination
      containing 1 or 2 mg of rosiglitazone plus 500 mg of metformin (hydrochloride)
      was launched onto the French market in October 2004. (4) The indication for
      rosiglitazone was extended to include its use as triple-agent therapy in
      combination with metformin and a glucose-lowering sulphonylurea. (5) No clinical
      trials assessing effects on mortality or morbidity have evaluated rosiglitazone
      or pioglitazone in combination with other oral antidiabetic drugs. (6) Several
      trials have compared the glucose-lowering effects of dual-agent therapy using
      rosiglitazone or pioglitazone plus a glucose-lowering sulphonylurea or metformin
      versus dual-agent therapy with metformin and a glucose-lowering sulphonylurea.
      (7) These clinical trials indicate that in terms of HbA1c level, dual-agent
      therapy based on rosiglitazone or pioglitazone is about as effective as
      combination therapy with metformin plus a glucose-lowering sulphonylurea. (8) The
      main known adverse effect of pioglitazone and rosiglitazone is water-sodium
      retention, which can provoke oedema and haemodilution anaemia, and can aggravate
      or reveal heart failure. (9) Pioglitazone has a positive effect on the lipid
      profile, whereas rosiglitazone increases the LDL-cholesterol level. (10) Dual
      agent therapy with pioglitazone and a sulphonylurea causes more weight gain than
      metformin plus a sulphonylurea. (11) Several trials have assessed triple-agent
      regimens containing a glitazone. Three placebo-controlled double-blind trials
      have tested pioglitazone (one trial, nearly 300 patients) or rosiglitazone (two
      trials, about 1200 patients) for 12 to 26 weeks in patients whose glycaemia was
      poorly controlled by dual-agent therapy with a sulphonylurea plus metformin. The
      glycated haemoglobin level fell by 0.3% to 1.1% (in absolute values), depending
      on the trial and the dosage, but at a cost of the usual adverse effects such as
      weight gain, anaemia and oedema. Three unblinded trials have compared oral triple
      agent regimens containing glitazone versus insulin plus metformin, alone or in
      combination with a glucose-lowering sulphonylurea; the treatment including
      glitazone was no more effective in terms of the glycated haemoglobin level, but
      was associated with an increase in adverse effects and dropouts. (12) Given the
      limited clinical data available in early 2005, pioglitazone and rosiglitazone
      have no place in the management of type 2 diabetes.

PMID- 16106596
TI  - Olanzapine: new indication. Prevention of bipolar disorder: unconvincing trials.
AB  - (1) Lithium, the standard preventive treatment for patients with bipolar
      disorder, reduces the number of relapses and suicide attempts. (2) Olanzapine is
      the first neuroleptic to be approved in France for prevention of relapse in
      patients with bipolar disorder. Many neuroleptics are already used for this
      indication but their efficacy has not been established in comparative clinical
      trials. (3) One placebo-controlled double-blind trial involved 361 patients who
      were treated just after recovering from a manic episode. The trial was supposed
      to last 48 weeks, but only 146 patients were treated for more than 8 weeks.
      Therefore, the trial results, including an observed effect on mania, cannot be
      interpreted to imply long-term prevention. (4) One double-blind trial compared
      olanzapine plus a mood stabiliser with placebo plus a mood stabiliser in 344
      patients who had recovered from an acute episode. Only 21 patients completed the
      12-month trial, and the percentage of patients who had relapses (manic or
      depressive) did not differ significantly between the groups. (5) In a third
      double-blind trial, 431 patients in remission from a manic episode after
      treatment with olanzapine + lithium were treated for 12 months with lithium or
      olanzapine. This trial suggested that olanzapine was more effective in preventing
      depressive and manic relapses (30% of patients, compared to 38.8% with lithium),
      but only 171 patients completed the trial. Most dropouts were due to adverse
      events (19% with olanzapine, 26% with lithium). The impact of treatment on
      suicide risk was not studied. (6) In a fourth study, 101 patients in remission
      from a mixed or manic episode continued their initial treatment with olanzapine
      or sodium divalproate in double-blind manner for 11 months. The risk of relapse
      was not significantly different between the groups, but the study sample size was
      too small to tell whether or not the treatments were equally effective. (7)
      Trials focusing on prevention of relapse in patients with bipolar disorder
      confirmed the known adverse effects of olanzapine, including weight gain and QTc
      prolongation. Olanzapine was associated with more weight gain and sedation than
      lithium. Hyperglycaemia occurring on olanzapine can cause life-threatening
      ketoacidosis. (8) Lithium remains the standard treatment for preventing recurrent
      bipolar disorder. There is no firm evidence that olanzapine is more effective
      than a mood stabiliser after lithium failure, or that it boosts the efficacy of
      lithium.

PMID- 16106597
TI  - Hasty approval, more withdrawals.
AB  - Two studies have shown that in the 1990s the number of market withdrawals due to
      adverse effects increased while the time regulatory agencies have taken to
      approve new drugs decreased. More recent examples confirm that hasty approvals
      place patients at an increased risk of serious adverse effects.

PMID- 16106598
TI  - Venlafaxine and cardiac effects.

PMID- 16106599
TI  - Ischaemic stroke: acute-phase drug therapy. Mostly aspirin and heparin.
AB  - (1) In the acute phase of ischaemic stroke, antiplatelet or anticoagulant
      treatments reduce the risk of recurrence and pulmonary embolism, but carry a risk
      of haemorrhagic transformation. (2) Aspirin has been tested in several placebo
      controlled trials and has a positive risk-benefit balance, preventing about 5
      deaths per 1000 patients with ischaemic stroke. Aspirin must be given as soon as
      computed tomography has ruled out intracerebral haemorrhage, unless thrombolytic
      treatment is planned. (3) Heparin has as many potential benefits as risks: it
      tends to be beneficial at low doses but harmful at high doses. Low-dose heparin
      therapy appears to be justified, especially for patients with emboligenic heart
      disease, tight carotid stenosis, or at risk of pulmonary embolism. Higher-dose
      heparin is only warranted for the rare patient with a high thrombotic risk. (4)
      Some thrombolytic drugs can reduce the frequency and severity of complications,
      but their use carries a high immediate risk of aggravation or death by
      haemorrhagic transformation. Alteplase has a somewhat positive risk-benefit
      balance in certain highly specific situations: for example, in some patients with
      persistent ischaemic stroke who are treated within three hours of onset, and
      without signs of severe stroke or risk factors for bleeding (high blood pressure,
      aspirin use). (5) Clinical trials have shown that routine use of
      "neuroprotective" treatments (calcium channel blockers, haemodilution, parenteral
      magnesium, oxygen therapy) does not reduce the risk of death or disability. (6)
      Arterial hypertension frequently occurs in the immediate aftermath of stroke, and
      then generally subsides. Few clinical trials have evaluated the use of
      antihypertensive drugs in this setting and there is little evidence of benefit.
      One trial showed that a sudden drop in blood pressure led to neurological
      aggravation. Antihypertensive drugs should only be used in stroke patients with
      severe hypertension or cardiac complications. (7) Cerebral oedema is an important
      cause of death after stroke: treatments (especially mannitol, mechanical
      ventilation and neurosurgery) have been poorly evaluated. (8) Other treatments
      recommended only for patients with persistent complications include oxygen
      therapy, antibiotics, paracetamol, insulin, and anticonvulsants. (9) A
      controversial meta-analysis suggested that management by a specialised
      multidisciplinary team reduced the mid-term risk of death and disability in
      comparison with management in a non specialised unit.

PMID- 16106600
TI  - The neurobiology of persistent pain and its clinical implications.
AB  - Descending modulation of nociception is enhanced following tissue injury. These
      changes include suppression and facilitation of nocifensive behavior and spinal
      dorsal horn hyperexcitability originating at brain stem sites. Evidence has been
      presented that such descending modulation undergoes time-dependent changes
      following persistent inflammation. There is an initial decrease and a subsequent
      increase in the excitability of neurons in the RVM involving facilitation and
      inhibition. The enhanced descending modulation includes changes in the activation
      and gene expression of the NMDA and AMPA excitatory amino acid receptors. In vivo
      electrophysiological recordings further reveal a change in the response profile
      of RVM neurons during the development of inflammation: cells previously
      unresponsive to nociceptive stimuli, exhibit response profiles characteristic of
      pain-modulating neurons. These findings demonstrate activity-dependent plasticity
      in brain stem circuits that includes changes in excitatory amino acid receptor
      activation and sensitivity and a phenotypic switch of some RVM neurons.

PMID- 16106601
TI  - Unmyelinated nerves, challenges, and opportunities: skin biopsy and beyond.

PMID- 16106602
TI  - The irritable human nociceptor under microneurography: from skin to brain.

PMID- 16106603
TI  - Reflex sympathetic dystrophy and causalgia.

PMID- 16106604
TI  - Central mechanisms of pain perception.
AB  - Mechanisms of human nociception can be studied by the use of CO2 laser
      stimulation, which selectively activates nociceptive receptors, and by the use of
      various noninvasive techniques. In addition to the contralateral thalamus, at
      least several cortical areas including the contralateral SI, bilateral SII,
      anterior cingulated cortex, and insular cortices are involved in the pain
      sensation/perception. Pain perception (Fig. 8) is unique because these cortical
      structures seem to be activated in parallel at nearly the same latency after the
      stimulus presentation. SI seems to play a role in basic pain processing while SII
      and insula are involved in higher functions of pain perception. Emotional aspects
      of pain perception are mediated by anterior cingulate cortex and posterior
      insula/parietal operculum.

PMID- 16106605
TI  - The role of the thalamus in pain.

PMID- 16106606
TI  - The role of secondary somatosensory cortex and insula in pain.

PMID- 16106607
TI  - Neuroimaging of pain.

PMID- 16106608
TI  - Therapeutic approaches to low back pain.
AB  - There has been a great deal of intelligent, insightful, and useful work conducted
      on understanding how individuals perceive pain; however, there remains a great
      deal more to be learned about how the complex interplay between pain and an
      individual's psychological and social experience affects the degree of suffering
      and disability associated with injury. Clinicians treating low back pain have an
      obligation to their patients to maintain an understanding of the ever-increasing
      amount of information available on spinal mechanics, pathophysiology, and
      diagnostic and treatment strategies. Clinicians have an equally important
      obligation in understanding the true role that pain is playing in their patients'
      lives. Clinical care of patients with spinal disorders needs to be directed
      towards optimizing function. In order to do this, it is essential to obtain the
      information needed to identify and overcome barriers to improvement, and to
      provide treatment in a compassionate, coordinated fashion that addresses the
      multidimensional needs of the individual.

PMID- 16106609
TI  - Nerve excitability studies: past, present, future?

PMID- 16106610
TI  - Quantitation of EMG, what and why.

PMID- 16106611
TI  - Clinical utility of pain--laser evoked potentials.

PMID- 16106612
TI  - Surface EMG: how far can you go?

PMID- 16106613
TI  - Motor unit number estimation: new techniques and new uses.
AB  - MUNE is a unique neurophysiologic tool because it can quantitatively estimate the
      number of motor neurons innervating a muscle or group of muscles. All other
      neurophysiologic techniques are influenced by collateral reinnervation and
      provide only a qualitative estimate of motor unit loss. Further, the S-MUPs
      obtained with MUNE provide quantitative information about the whole motor unit.
      Other routine neurophysiologic techniques provide information restricted to a
      portion of the motor unit. These unique features of MUNE have been applied to
      neurogenic disorders to yield a better understanding of disease processes.
      Various modifications are being developed that will provide more data and ease of
      use. It is anticipated that the availability of MUNE on EMG machines will grow
      and it use will expand from a research tool to a routine neurophysiologic test.

PMID- 16106614
TI  - Techniques in pediatric neurophysiology.

PMID- 16106615
TI  - Antibody-mediated disorders of neuromuscular transmission.

PMID- 16106616
TI  - Botulinum toxin mechanisms of action.

PMID- 16106617
TI  - Electrophysiologic tests of neuromuscular transmission.

PMID- 16106618
TI  - Recent considerations in the etiopathogenesis of ALS.

PMID- 16106619
TI  - Conduction block in demyelinated axons precipitated by normally innocuous
      physiological processes.

PMID- 16106620
TI  - Peripheral neuropathies in human immunodeficiency virus infection.

PMID- 16106621
TI  - The genetics of amyotrophic lateral sclerosis (ALS).

PMID- 16106622
TI  - Genetic evaluation of inherited motor/sensory neuropathy.
AB  - Inherited disorders of peripheral nerves represent a common group of neurologic
      diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically
      heterogeneous group of chronic demyelinating polyneuropathies with loci mapping
      to chromosome 17 (CMT1A), chromosome 1 (CMT1B), chromosome 16 (CMT1C) and
      chromosome 10 (CMT1D). CMT1A is most often associated with a tandem 1.5-megabase
      (Mb) duplication in chromosome 17p11.2-p12. In rare patients it may result from a
      point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is
      associated with point mutations in the myelin protein zero (Po or MPZ) gene.
      Mutations in the SIMPLE gene cause CMT1C, and CMT1D is the result of mutations in
      the early response 2 (ERG2 or Krox-20) gene. An X-linked form of CMT1 (CMT1X)
      maps to Xq13 and is associated with mutations in the connexin32 (Cx32) gene.
      Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy that maps to
      chromosome 1p35-p36 (CMT2A), chromosome 3q13-q22 (CMT2B), chromosome 7p14
      (CMT2D), chromosome 8p21 (CMT2E), chromosome 1q22-q23 (CMT2F) or chromosome 3q13
      (CMT2G). Two X-linked forms of CMT2 have been reported (CMT2XA and CMT2XB), but
      the genes remain unidentified. An area that has recently expanded is the
      identification of autosomal recessive forms of CMT type 1 and 2. Of the eight
      recessive forms of CMT1 that have been identified to date, only two have been
      fully characterized at the molecular level (CMT1 AR B 1 and CMT1 AR D). Point
      mutations were found in the myotubularin-related protein-2 (MTM2) gene for CMT1
      AR B1. CMT1 AR D is the result of point mutations in the N-myc downstream
      regulated gene 1 (NDRG1). Dejerine-Sottas disease (DSD), also called hereditary
      motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset
      demyelinating polyneuropathy syndrome that may be associated with point mutations
      in either the PMP22 gene, PO gene, EGR2 gene or the PRX gene (for the recessive
      form). It shares considerable clinical and pathological features with CMT1.
      Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal
      dominant disorder that results in a recurrent, episodic demyelinating neuropathy.
      HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-p12 that results
      in reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal
      duplication/deletion syndromes that originate from unequal crossover during germ
      cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to
      chromosome 8q, 10q and 11q.

PMID- 16106623
TI  - Imaging nerve and muscle with ultrasound.
AB  - Over the last two decades significant advances in ultrasound have made it
      possible for investigators to image and interpret pathologic changes in muscle
      and nerve. In addition to being able to assess the pathologic changes in these
      structures themselves, ultrasound also provides the unique ability to identify
      anatomic lesions responsible for nerve or muscle injury. They can be correlated
      with changes in neural structures or affected muscles. Like electrodiagnostic
      studies, ultrasound is portable and inexpensive, but it is even less invasive,
      and surprisingly sensitive in detecting a variety of unusual and common causes of
      neuromuscular dysfunction. Given recent developments in the field, ultrasound
      shows promise as the technique most suitable for clinical neurophysiologists and
      neuromuscular clinicians in the growing field of imaging. Such involvement is
      required to best adopt and exploit the potential of imaging for the research and
      clinical evaluation of neuromuscular disorders.

PMID- 16106624
TI  - Update on diagnosis and treatment of hereditary and acquired polyneuropathies in
      childhood.

PMID- 16106625
TI  - The role of electromyography in the management of obstetric brachial plexus
      palsies.

PMID- 16106626
TI  - Clinical electrophysiologic tests and genotype correlations in muscle
      channelopathies.

PMID- 16106627
TI  - Molecular pathogenesis of inflammatory myopathies and future therapeutic
      strategies.

PMID- 16106628
TI  - Mitochondrial disorders.
AB  - Although mitochondrial disorders have been known for more than thirty years, a
      major breakthrough in their understanding came much later with the discovery of
      an impressive number of mutations in mitochondrial DNA (mtDNA). Partial
      deletions, duplications, or maternally inherited point mutations of mtDNA have
      been associated with well-defined clinical syndromes. Given the complexity of
      mitochondrial genetics and biochemistry, the clinical manifestations of
      mitochondrial disorders are extremely heterogeneous. They range from lesions of
      single tissues or structures, such as the optic nerve in Leber's hereditary optic
      neuropathy, or the cochlea in maternally-inherited non-syndromic deafness, to
      more widespread lesions including myopathies, encephalomyopathies,
      cardiomyopathies, or complex multisystem syndromes. An increasing number of
      nuclear disease genes have been discovered in association with syndromes caused
      by oxidative phosphorylation failure. These advances provide both diagnostic
      tools and new pathogenetic insights in a rapidly expanding area of neurogenetics.

PMID- 16106629
TI  - Immunopathology and molecular genetics of dystrophinopathies.

PMID- 16106630
TI  - Genotype-phenotype correlations in hereditary muscle diseases. Implications for
      diagnosis and treatment.

PMID- 16106631
TI  - The utility of MRI in the evaluation of myopathy.

PMID- 16106632
TI  - Microneurographic assessment of sympathetic nerve traffic.

PMID- 16106633
TI  - Waveform of sympathetic skin response.

PMID- 16106634
TI  - Laboratory evaluation of autonomic function.

PMID- 16106635
TI  - Assessment of cardiovascular autonomic function.

PMID- 16106636
TI  - Brain stimulation and epilepsy: novel approaches for seizure control.

PMID- 16106637
TI  - Current role of EEG in the presurgical evaluation of temporal lobe epilepsy
      patients.
AB  - Despite all new developments in methodologies to investigate epileptic patients,
      EEG continues to play a central and irreplaceable role in clinical epileptology,
      especially in the presurgical evaluation of medically intractable epilepsies.
      Temporal lobe epilepsy is the most prevalent type of epileptic syndrome, and also
      the most frequent type of surgically treatable epilepsy. Non-invasive and
      invasive EEG methodologies are essential in the selection of surgical candidates.
      More recently there has been a trend towards the use of exclusively noninvasive
      methodologies. In this chapter we describe our current view on the role of
      diverse EEG methodologies in the presurgical evaluation of mesial temporal lobe
      epilepsies, addressing, in particular, the role of foramen ovale electrodes
      which, probably, needs to be reassessed in view of the unprecedented evolution of
      MRI.

PMID- 16106638
TI  - Models of focal epilepsy.
AB  - Focal symptomatic epilepsy is the most common and most refractory form of human
      epilepsy and is an important subject of basic research. Although advanced
      diagnostic technologies and epilepsy surgery facilities are providing increasing
      opportunities to carry out investigations directly on patients with focal
      epilepsy, inherent limitations make research with animal models essential to
      elucidate basic mechanisms, improve diagnosis, and test potential therapies.
      Numerous animal models are available, but proper use requires that they be
      validated for specific investigative purposes and, preferably, studied along with
      patients, employing reiterative parellel experimental paradigms. Clinical
      research establishes the critical questions that cannot be completely answered
      with human investigation, while results of animal research carried out to resolve
      these questions must be reexamined clinically to confirm their relevance to the
      human condition. Better and cheaper animal models are necessary for optimum cost
      effective parallel research activities, which includes not only models of
      specific types of acute epileptic seizures, and chronic epilepsy, but models of
      component parts of seizures and epilepsy that can be used as surrogate, or
      biological, markers of epileptogenesis and epileptogenicity. Appropriate use of
      markers such as FR could greatly reduce the expense, and time required, to
      produce the necessary research results.

PMID- 16106639
TI  - Physiology of frontal lobe seizures: pre-ictal, ictal and inter-ictal
      relationships.

PMID- 16106640
TI  - The idiopathic generalized epilepsies across life.

PMID- 16106641
TI  - Models for generalized seizures.
AB  - It is clear that a variety of gene defects can result in absence seizures. In
      addition, the problem is complicated by observation that the behavioral and EEG
      phenotype in some of the models is highly dependent on pedigree. Despite these
      difficulties, advances in molecular-genetic techniques coupled with
      electrophysiological studies are likely to be highly revealing. While the
      relationship between the rat and mice models and the human condition thus far
      remains tenuous, insights from the animal models have already been very helpful
      in choosing antiepileptic drugs and providing insights into the pathophysiology
      of the seizures.

PMID- 16106642
TI  - Myoclonic epilepsies: syndromes and their treatment.

PMID- 16106643
TI  - The reflex epilepsies with emphasis on photosensitive epilepsy.

PMID- 16106644
TI  - The genetics of oscillations in the human brain.

PMID- 16106645
TI  - Solving the neuroimaging puzzle: the multimodal integration of
      neuroelectromagnetic and functional magnetic resonance recordings.
AB  - In this chapter, advanced methods for the modeling of human cortical activity
      from combined high-resolution electroencephalography (EEG) and functional
      magnetic resonance imaging (fMRI) data are reviewed. These methods include a
      subject's multicompartment head model (scalp, skull, dura mater, cortex)
      constructed from magnetic resonance images, multidipole source model, and
      regularized linear inverse source estimates. Determination of the priors in the
      resolution of the linear inverse problem was performed with the use of
      information from the hemodynamic responses of the cortical areas as revealed by
      block-designed (strength of activated voxels) and event-related (coupling of
      activated voxels) fMRI. As an example, these methods were applied to EEG (128
      electrodes) and fMRI data, which were recorded in separate sessions while normal
      subjects executed voluntary right one-digit movements.

PMID- 16106646
TI  - Functional MR imaging: from the BOLD effect to higher motor cognition.
AB  - The key contributions of functional imaging to our understanding of the human
      motor system and higher motor disorders are reviewed in this chapter. Following a
      short introduction into the method of functional magnetic resonance imaging
      (fMRI), some core aspects of the human motor system (multiple nonprimary motor
      areas, the mirror neuron system, intraparietal multimodal cortex) are
      highlighted. Finally, the convergence (and divergence) of functional imaging and
      neurological data from patients with lesions of the motor system is discussed
      with special emphasis to how this informs our current knowledge of the
      pathophysiology of higher motor disorders.

PMID- 16106647
TI  - Alternative EEG monitoring for temporal lobe epilepsy.

PMID- 16106648
TI  - Advances in EEG telemetry.

PMID- 16106649
TI  - Intracranial monitoring.

PMID- 16106650
TI  - Aids to telemetry in the presurgical evaluation of epilepsy patients: MRI, MEG
      and other non-invasive imaging techniques.

PMID- 16106651
TI  - The development of sleep in neonates.

PMID- 16106652
TI  - Sleep in aging and neurodegenerative diseases.

PMID- 16106653
TI  - The microstructure of sleep.

PMID- 16106654
TI  - Adult sleep disorders.

PMID- 16106655
TI  - The cortical control of movement: a clinical perspective.

PMID- 16106656
TI  - Contribution of subcortical motor pathways to the execution of ballistic
      movements.
AB  - Preparation for a voluntary ballistic movement in the context of a simple
      reaction time task (SRT) involves enhancement of excitability in subcortical
      motor tracts. However, little is known about the characteristics of that
      preparation, how long the excitability enhancement takes place, and whether it is
      present not only in SRT but also in more attention requiring tasks as those
      involved in choice reaction time (CRT) paradigms. In the study presented here, we
      used the effects induced by a startling auditory stimulus (SAS) on reaction time
      (the StartReact effect) as a probe for assessing motor preparation of subcortical
      tracts. Subjects were requested to make a ballistic wrist extension movement to
      the presentation of a visual imperative signal. A SAS was randomly introduced in
      25% of trials at 0, -50, -100, -200, -300, -400, and -500 ms. We measured
      reaction time at the onset of the first burst of EMG activity in the agonist
      muscle, the configuration of the EMG activity in agonist and antagonist muscles,
      and whether the responses were congruent with the side of the stimulus. At the
      interval of 0 ms, the SAS induced a shortening of the reaction time similarly in
      CRT and SRT. The duration of the preparation time was significantly longer for
      SRT (421 +/- 71 ms) than for CRT (138 +/- 63 ms). Some degree of co-activation
      was present in all subjects in CRT trials without SAS, and increased considerably
      in trials with SAS. Isolated or significantly predominant preparation of the
      wrong hand was observed in 32% of the trials at an interval of 0 ms, and in 44%
      of trials in the remaining intervals. Preparation errors consisting of the
      presence of a well defined triphasic pattern were very variable, although more
      frequently seen in the dominant hand (64%) than in the non-dominant hand (36%).
      Our results indicate that preparation of subcortical motor pathways occurs before
      the execution of ballistic movements in the context of a CRT paradigm, but its
      duration is shorter than in SRT tasks. Preparation for CRT may be biased towards
      the dominant hand but factors other than laterality have also to be taken into
      account.

PMID- 16106657
TI  - Paired associative stimulation.
AB  - Paired associative stimulation (PAS) refers to a paradigm consisting of slow-rate
      repetitive low-frequency median nerve stimulation combined with transcranial
      magnetic stimulation (TMS) over the contralateral motor cortex. This protocol has
      been shown to induce plastic changes of excitability in the human motor cortex.
      Its principles of design were shaped after associative long-term potentiation
      (LTP) in experimental animals, a cellular mechanism likely to be relevant for
      learning and memory. PAS-induced changes of cortical excitability share a number
      of physiological properties with LTP. Of particular importance is the fact that
      the sign of PAS-induced changes of the size of amplitudes of the motor evoked
      potentials (MEPs) depends on the exact interval between the afferent and the
      magnetic pulse during the intervention. A number of observations suggest that PAS
      induced excitability changes may have functional significance. PAS-induced
      plasticity may contribute to elucidating the pathogenesis of neurological
      disorders where neuroplasticity is thought to have a pathogenetic role. Finally,
      PAS-induced plasticity may itself have therapeutic potential.

PMID- 16106658
TI  - Corticomuscular and intermuscular frequency analysis.

PMID- 16106659
TI  - Cortico-cortical coherence.

PMID- 16106660
TI  - Brain-computer communication based on the dynamics of brain oscillations.
AB  - This chapter presents a review of brain-computer communication based on motor
      imagery and the dynamics of brain oscillations. The concept of motor imagery as
      experimental strategy and the two different modes of operation a brain-computer
      interface can have are explained. An EEG based brain switch that can control a
      FES-induced hand grasp of a tetraplegic and an approach towards an ECoG based
      brain switch are presented.

PMID- 16106661
TI  - Development of neuromotor prostheses for humans.

PMID- 16106662
TI  - Brain-computer interfaces (BCIs) for communication and control: a mini-review.

PMID- 16106663
TI  - The speed of visual cognition.
AB  - Intracranial electrophysiological recordings in primates showed repeatedly that
      neurons in several cortical areas are activated very early after visual stimulus
      presentation, practically at the same time (or even before) the activation of
      primary sensory neurons. Even neurons at the highest hierarchical levels of the
      visual system are activated in less than 100 ms. These findings challenge the
      classical interpretation of human evoked potential (EP) data that assume that the
      first, "exogenous", EP components from 50 to 150 ms reflect the initial volley of
      sensory activation in the striate and extrastriate visual cortex and are not yet
      influenced by cognitive task demands. Indeed, several recent EP studies using
      analysis methods that go beyond the classical approach of defining "components"
      at certain scalp positions indicate that highly complex stimulus features can
      influence EP responses within the first 100 ms. This indicates that sophisticated
      cognitive processing is much faster than previously thought and opens new
      perspectives with respect to the role of both, bottom-up as well as top-down
      mechanisms in visual processing.

PMID- 16106664
TI  - Speech-sound encoding: physiological manifestations and behavioral ramifications.

PMID- 16106665
TI  - Neural network for novelty processing.

PMID- 16106666
TI  - Contribution to a neurophysiology of consciousness.

PMID- 16106667
TI  - Sensory and cognitive evoked potentials in the prognosis of coma.

PMID- 16106668
TI  - EEG monitoring of comatose patients in the intensive care unit.

PMID- 16106669
TI  - Stupor and coma: metabolic encephalopathies.

PMID- 16106670
TI  - Stupor and coma: pathophysiology of hypoxia--ontogenetic aspects.
AB  - There are several levels of O2 deprivation with different possibilities of
      adaptation and compensation. All of them appear to be highly conservative in
      phylogenesis and are active early in ontogenetic development. The coordinated
      structural and functional responses to systemic and/or local hypoxia form the
      basis for individual adaptation to environmental requirements and pathological
      threat.

PMID- 16106671
TI  - Measures of cortical inhibition in health and disease.

PMID- 16106672
TI  - LTP-like plasticity in human motor cortex.

PMID- 16106673
TI  - Outlasting excitability shifts induced by direct current stimulation of the human
      brain.
AB  - tDCS appears to be a promising tool in neuroplasticity research with some
      perspectives in clinical neurophysiology. It is closely related to modulation of
      cortical excitability and activity which are key mechanisms for modulating
      neuroplasticity. Long-term potentiation and long-term depression-like effects
      have been shown to be involved in learning processes in animal studies so far.
      Stimulation with weak direct currents is capable of inducing stimulation-polarity
      dependent, prolonged, diminutions or elevations of cortical activity and
      excitability, most probably elicited by a hyper- or depolarisation of resting
      membrane potentials. Moreover, these modulations are functionally important,
      since they affect learning processes and epileptic activity. Here excitability
      changes have been accomplished in the human by non-invasive transcranial direct
      current stimulation (tDCS). They share some important features with these well
      known neuroplastic changes: The duration of the effects depends on stimulation
      duration and intensity, they are of intracortical origin, and the prolonged
      effects depend on NMDA-receptor activity. Thus, this technique is a promising
      method in the field of neuroplastic research in animals and humans and could
      evolve as a therapeutic tool in some neuro-psychiatric disorders which benefit
      from modulation of cortical excitability.

PMID- 16106674
TI  - rCBF changes elicited by rTMS over DLPFC in humans.
AB  - Recently, repetitive TMS (rTMS) has been used as a potential treatment for
      depression. Several studies have shown antidepressant effects of rapid rTMS over
      the left dorsolateral prefrontal cortex (DLPFC), whereas some studies suggested
      the effectiveness of slow rTMS over the right DLPFC. Despite the growing interest
      in therapeutic application of rTMS, the precise mechanisms for rTMS over the
      DLPFC are still unknown. To clarify these mechanisms for slow rTMS over the right
      prefrontal cortex, we measured regional cerebral blood flow (rCBF) during real or
      sham rTMS and after stimulation using repeated l5O-labeled H2O PET scanning in
      seven healthy subjects. We found that slow rTMS over the right DLPFC could
      produce significant rCBF increase in the ipsilateral anterior cingulate cortex
      (ACC) during stimulation as compared with sham stimulation. The lasting
      activation occurred in the ipsilateral medial prefrontal cortex, contralateral
      ventrolateral PFC, and the contralateral ventral striatum. These data indicate
      that slow rTMS is able to produce rCBF changes in the paralimbic system and
      frontal cortex. We conclude that the lasting effect on the ventral striatum
      should reflect modulatory effects of rTMS over the DLPFC on the meso-limbic
      dopaminergic system that must play critical roles in antidepressant effects.

PMID- 16106675
TI  - Brain stimulation: current clinical indications and future prospects.

PMID- 16106676
TI  - How does DBS work?
AB  - Deep brain stimulation (DBS) produces striking effects in patients with various
      disorders including Parkinson's disease and dystonia, yet its precise mechanism
      of action is not clear. Because the clinical benefits of lesioning target
      structures such as the thalamus, globus pallidus and subthalamic nucleus appear
      to be similar to those achieved by chronic application of stimulation at these
      structures, it has been surmized that deep brain stimulation produces a
      functional inactivation or block of the target. This simplistic proposal has
      supporting and detracting evidence. In the present work we consider the mechanism
      of action of DBS and provide arguments for and against the stimulation or
      inhibition of target neural structures.

PMID- 16106677
TI  - Transcranial magnetic stimulation in the management of pain.
AB  - Drug-resistant, neurogenic pain can be treated by chronic motor cortex
      stimulation using surgically-implanted epidural electrodes. High-frequency,
      subthreshold repetitive transcranial magnetic stimulation (rTMS) of the motor
      cortex was shown to be able to produce antalgic effects, at least transiently, in
      patients with chronic pain. Nevertheless, other cortical targets than the primary
      motor cortex are tempting (parietal or prefrontal areas for instance) for the
      management of pain and need to be studied. Motor cortex TMS was also found to
      modulate non-nociceptive sensory perception as well as acutely provoked pain in
      healthy subjects by means of a single conditioning pulse or repeated trains. On
      the contrary, spontaneous or provoked pain was shown to modify motor cortex
      excitability, as assessed by TMS technique. Taking into account all these
      observations, it appears that motor cortex function and pain process are closely
      related and that TMS is a potent tool to explore and to understand this
      relationship. Beyond this physiological purpose, rTMS could be useful to control
      episodes of neurogenic pain of limited duration or to select patients for the
      surgical implantation of a cortical stimulator.

PMID- 16106684
TI  - [Relationships in all the states].

PMID- 16106685
TI  - [Contractual relationships from now on in institutions].

PMID- 16106686
TI  - [Favoring a tripartite participative relationship between
      residents/families/nurses].

PMID- 16106687
TI  - [Mediation of conflicts between families and nurses].

PMID- 16106688
TI  - [The nurse, a key actor in geriatric institutions].

PMID- 16106689
TI  - [The nurse's aide, a confidant privileged by proximity].

PMID- 16106690
TI  - [Council of Social Life, a new place for families and residents].

PMID- 16106691
TI  - [Helping students to have another view of aging].

PMID- 16106692
TI  - [Sleep and sleep disorders during aging].

PMID- 16106693
TI  - [Quality of sleep and management of nocturnal continence in the elderly in the
      hospital or institution].

PMID- 16106694
TI  - [What legal protection for dementia patients?].

PMID- 16106695
TI  - [Oral hygiene in institutions].

PMID- 16106696
TI  - [Managing simple deglutition disorders in gerontology].

PMID- 16106697
TI  - Extraction and determination of sulfonamides, macrolides, and trimethoprim in
      sewage sludge.
AB  - Pressurized liquid extraction (PLE) was optimized and validated for the
      determination of sulfonamide and macrolide antimicrobials and trimethoprim in
      sewage sludge samples. A mixture of water/methanol (50:50, v/v) was found as the
      most efficient extraction solvent. A temperature of 100 degrees C and a pressure
      of 100 bar were chosen for extraction. Two cycles of 5 min each efficiently
      extracted at least 97% of the total extractable amount of all studied analytes
      from activated sludge. The limits of quantification (S/N= 10) varied between 3
      and 41 microg/kg dry weight (dw) and the relative recoveries ranged between 78
      and 142%. Additionally, the influence of pH and different LC/MS/MS systems on the
      absolute recoveries was assessed. Of the investigated antimicrobials
      sulfapyridin, sulfamethoxazole, trimethoprim, azithromycin, clarithromycin and
      roxithromycin were detected in municipal sewage sludge samples. Concentrations in
      activated sludge ranged up to 197 microg/kgdw. In comparison, results obtained by
      ultrasonic solvent extraction were significantly lower for sulfonamides and in
      tendency lower for macrolides.

PMID- 16106698
TI  - Usefulness of D-optimal designs and multicriteria optimization in laborious
      analytical procedures. Application to the extraction of quinolones from eggs.
AB  - An analytical method has been developed to extract ciprofloxacin and enrofloxacin
      from eggs. The aim of this work is to determine the experimental conditions of
      extraction providing high recoveries with small standard deviations. An
      experimental design based on the D-optimality criterion and replicated three
      times was built to evaluate the effect of five factors related to the extraction
      which is the most inaccurate stage of the procedure. This non-classical design is
      needed because there are several practical constraints: (i) the extraction
      procedure is time-consuming, quinolones are not stable and the design must be
      performed in a single working session. (ii) The tube capacity of the centrifuge
      is 6, so the number of experiments will be 6 or a multiple of 6. In the optimal
      experimental conditions, the extraction is performed once with 5 ml of methanol.
      Then, fatty acids are removed with a mixture of hexane/ether. Analytes are
      finally separated and detected by HPLC-fluorescence without the additional step
      of purification by solid-phase extraction (SPE). Under these conditions, the mean
      recovery is 64% and 70% and the standard deviation 5% and 4% for ciprofloxacin
      and enrofloxacin, respectively. The capability of decision, CCalpha, is 3.1 and
      2.8 microg kg(-1) of ciprofloxacin and enrofloxacin, respectively. The capability
      of detection, CCbeta, is 7.8 and 7.0 microg kg(-1) of ciprofloxacin and
      enrofloxacin, respectively. In both cases the probabilities of false positive,
      alpha, and of false negative, beta, were fixed at 0.05.

PMID- 16106699
TI  - Determination of triazines and dealkylated and hydroxylated metabolites in river
      water using a propazine-imprinted polymer.
AB  - A molecularly imprinted polymer (MIP) obtained by precipitation polymerisation
      using propazine as template has been employed as sorbent for the solid phase
      extraction of triazines and some of their hydroxylated and dealkylated
      metabolites from river water. Three configurations were studied: (a) use of the
      propazine-MIP as a selective sorbent for the extraction of triazines directly
      from water; (b) use of mixtures of LiChrolut EN (a polymeric sorbent of styrene
      divinylbenzene) and propazine-MIP as sorbent, and (c) use of propazine-MIP as a
      clean-up sorbent for organic extracts obtained in a prior SPE procedure with
      LiChrolut EN. The former two configurations imply that the analytes pass through
      the propazine-MIP in aqueous medium, whereas in the latter case the analytes
      percolate through the propazine-MIP in an organic medium coming from the previous
      SPE step. Different types of water were tested to assess matrix effects. The
      analytical characteristics of the three configurations were evaluated.

PMID- 16106700
TI  - Determination of priority pesticides in baby foods by gas chromatography tandem
      quadrupole mass spectrometry.
AB  - A gas chromatography-tandem quadrupole mass spectrometry (GC-MS/MS) method for
      the determination of twelve priority pesticides, and transformation products
      (e.g. metabolites) specified in the EU Baby Food Directive 2003/13/EC is
      described. Prior to GC-MS/MS analysis, co-extractives were removed from
      acetonitrile extracts using dispersive solid phase extraction with octadecyl (200
      mg) and primary secondary amine (50 mg) sorbents. The clean up proved essential
      for the satisfactory long-term chromatographic performance during the analysis of
      a range of representative commercially pre-prepared baby food samples. Extracts
      spiked with pesticides at 1-8 microg kg(-1), yielded average recoveries in the
      range 60-113% with relative standard deviations less than 28%.

PMID- 16106701
TI  - Identification and quantitative determination of diphenylarsenic compounds in
      abandoned toxic smoke canisters.
AB  - Knowledge of the exact nature of the constituents of abandoned chemical weapons
      (ACW) is a prerequisite for their orderly destruction. Here we report the
      development of analytical procedures to identify diphenylchloroarsine (DA/Clark
      I), diphenylcyanoarsine (DC/Clark II) and related substances employed in one of
      the munitions known as "Red canister". Both DA and DC are relatively unstable
      under conventional analytical procedures without thiol derivatization.
      Unfortunately however, thiol drivatization affords the same volatile organo
      arsenic derivative from several different diphenylarsenic compounds, making it
      impossible to identify and quantify the original compounds. Further, diminishing
      the analytical interference caused by the celluloid powder used as a stacking
      material in the weapons, is also essential for accurate analysis. In this study,
      extraction and instrumental conditions have been evaluated and an optimal
      protocol was determined. The analysis of Red canister samples following this
      protocol showed that most of the DA and DC associated with pumice had degraded to
      bis(diphenylarsine)oxide (BDPAO), while those associated with celluloid were
      dominantly degraded to diphenylarsinic acid (DPAA).

PMID- 16106702
TI  - Simple and rapid method for cis- and trans-resveratrol and piceid isomers
      determination in wine by high-performance liquid chromatography using chromolith
      columns.
AB  - A simple and rapid HPLC method has been developed for simultaneous determination
      of the four resveratrol forms (aglycon and glycosidic) in a Grenache wine from
      Chateauneuf du Pape (Vaucluse). These analyses were achieved by using two
      commercial monolith HPLC columns and diode array detection. The method provided
      reliable separations at low pressure with a short analysis time. The limit of
      detection (LD) and limit of quantification (LQ) were calculated for each
      standard. The molecules were separated and quantified in a single run without any
      purification of the sample.

PMID- 16106703
TI  - Development of a ginkgo biloba fingerprint chromatogram with UV and evaporative
      light scattering detection and optimization of the evaporative light scattering
      detector operating conditions.
AB  - A fingerprint chromatogram of a standardized Ginkgo biloba extract is developed
      on a monolithic silica column using a ternary gradient containing water, iso
      propanol and tetrahydrofuran. For the detection, UV and evaporative light
      scattering (ELS) detectors are used, the latter allowing detection of the poor UV
      absorbing compounds as ginkgolides (A-C and J) and bilobalide in the extract. The
      complementary information between the UV and ELS fingerprint is evaluated. The
      ELS detector used in this study can operate in an impactor 'on' or 'off' mode.
      For each mode, the operating conditions such as the nebulizing gas flow rate, the
      drift tube temperature and the gain are optimized by use of three-level screening
      designs to obtain the best signal-to-noise (S/N) ratio in the final ELS
      fingerprint chromatogram. In both impactor modes, very similar S/N ratios are
      obtained for the nominal levels of the design. However, optimization of the
      operating conditions resulted, for both impactor modes, in a significant increase
      in S/N ratios compared to the initial evaluated conditions, obtained from the
      detector software.

PMID- 16106704
TI  - Determination of synthetic chelating agents in surface and waste water by ion
      chromatography-mass spectrometry.
AB  - Coupling of ion chromatography with electrospray mass spectrometry (IC-MS) is a
      simple, sensitive and quick method for the determination of polar organic traces
      in water samples without derivatization. Analysis of the chelating agents
      ethylenediamino tetraacetate (EDTA) and diethylenetriamino pentaacetate (DTPA) in
      aqueous samples was done by IC-MS on an anion exchange column after simple sample
      preparation steps. Quantification down to a concentration level of 1 microg L(-1)
      even in wastewater influents and effluents was achieved utilizing 13C marked
      internal standards and measuring the individual [M - H+]- and stable [M - 4H+ +
      Fe3+]- cluster ions. The method was validated against certified, but more time
      consuming routine methods. Applying this method a series of several European
      water samples were analyzed for EDTA and DTPA indicating their nature as polar
      persistent pollutants.

PMID- 16106705
TI  - Multi-residue method for the determination of thyreostats in urine samples using
      liquid chromatography coupled to tandem mass spectrometry after derivatisation
      with 3-iodobenzylbromide.
AB  - Thyreostats are banned compounds in Europe since 1981 (directive 81/602/EC)
      because of their carcinogenic and teratogenic properties. The control of their
      illegal use in breeding animals is amongst the most difficult because of their
      low molecular weight, high polarity and the existence of tautomeric forms. The
      analytical procedure described in this paper involves, after a derivatisation
      step with 3-iodobenzylbromide, the detection and identification at low level
      (microg/L) by LC-ESI(-)-MS/MS of eight thyreostats in various biological matrices
      (urine, muscle, liver, thyroid, animal feed, faeces and hair). The urine method
      has been validated according to the EU criteria (2002/657/EC decision): CCalpha
      and CCbeta were found in the range (0.1-5.2 microg/L) and (2.6-23.2 microg/L),
      respectively. The performances fulfil the requirements of the EU regarding the
      provisional minimum required performance limit (MRPL) fixed at 100 microg/L in
      urine.

PMID- 16106706
TI  - Liquid chromatography of polyoxyethylenes under critical conditions: a
      thermodynamic study.
AB  - Polyethylene glycols (PEG), fatty alcohol ethoxylates (FAE) and fatty acid
      polyglycol esters were analyzed by liquid chromatography under critical
      conditions (LCCC) on typical reversed phase columns in mobile phases consisting
      of methanol-water and acetone-water in the region of the critical adsorption
      point (CAP) for the oxyethylene unit. Critical conditions can be adjusted by
      varying the mobile phase composition or temperature. In methanol-water the
      temperature dependence is almost negligible, while it is much more pronounced in
      acetone-water. Critical conditions for the oxyethylene unit were realized on
      octadecyl phases in methanol-water containing 85.8 wt.% methanol and in acetone
      water at 89.6 wt.% acetone. In the van't Hoff plots the logarithm of the
      distribution coefficient was plotted versus the reciprocal temperature. In all
      plots straight lines were found, from slope and intercept of which the entropy
      and enthalpy changes were calculated. The relation of the thermodynamic
      parameters -deltaG/RT, -deltaH/RT, and deltaS/R to the numbers of A and B chain
      units in block copolymers AB and BAB at the CAP for A is studied both
      theoretically and experimentally. Various approaches for obtaining the critical
      temperature are discussed.

PMID- 16106707
TI  - Analysis of the nitrogen mustard mechlorethamine in topical pharmaceutical
      preparations by high-performance liquid chromatography.
AB  - Mechlorethamine in topical pharmaceutical formulations was derivatized with
      benzenethiol to form the disubstitution product and analyzed by normal-phase HPLC
      on silica gel using dibutyl phthalate as an internal standard. The derivatization
      reaction, purification, and isolation were conveniently performed in a single
      test tube. Analyses were successfully performed on three types of ointment
      formulations: anhydrous hydrophobic petrolatum-based ointments, anhydrous
      hydrophilic ointments, and hydrous hydrophilic ointments. Precision for the
      analysis of mechlorethamine standard or mechlorethamine in ointments ranged from
      0.08 to 0.52% RSD (n = 6). Recoveries from ointments spiked with 0.02%
      mechlorethamine hydrochloride were 98.4-100.4%. The chromatograms were clean,
      showing minimal or no interference from ointment excipients or reagents.

PMID- 16106708
TI  - Isolation and structure elucidation of phenolic compounds from longan (Dimocarpus
      longan Lour.) seed by high-performance liquid chromatography-electrospray
      ionization mass spectrometry.
AB  - High-performance liquid chromatography coupled with electrospray ionization mass
      spectrometry (HPLC-ESI-MS) analysis revealed the phenolics profile of longan
      (Dimocarpus longan Lour.) seed. Gallic acid, ellagic acid, monogalloyl-glucose,
      monogalloyl-diglucose, digalloyl-diglucose, penta- to heptagalloyl-glucose,
      ellagic acid-pentose conjugate, galloyl-HHDP (Hexahydroxydiphenoyl)
      glucopyranose, pentagalloy-HHDP-glucopyranose, procyanidin A-type dimer,
      procyanidin B2 and quercetin-3-O-rhamnoside were found to be present in longan
      seed along with a number of, as yet, unknown compounds. The results illustrate
      the rich array of phenolic compounds in longan seeds which could be utilized as
      health-beneficial bioactive compounds rather than just discarded as waste.

PMID- 16106709
TI  - Determination of mono- to octachlorobiphenyls in fish oil using florisil
      adsorption followed by headspace solid-phase microextraction and gas
      chromatography with time-of-flight mass spectrometric detection.
AB  - A simple and reliable method for the determination of polychlorinated biphenyls
      (PCBs) from mono- to octachlorobiphenyls in fish oil for dietary supplement is
      described. The method combines Florisil clean up and headspace solid-phase
      microextraction on 65 microm polydimethylsiloxane-divinylbenzene (PDMS-DVB).
      Analyte detection was carried out using GC-time-of-flight mass spectrometry (GC
      TOF-MS). Fifty three PCB congeners including the seven indicator PCBs (IUPAC Nos.
      28, 52, 101, 118, 138, 153 and 180) were analyzed. Under optimal conditions, the
      method detection limit (MDL) of each congener in the range from 0.8 to 31 ng/g
      was found. A certified reference material (BCR-349) was analyzed and it showed
      good agreement with the certified data.

PMID- 16106710
TI  - Comparison of shikimic acid determination by capillary zone electrophoresis with
      direct and indirect detection with liquid chromatography for varietal
      differentiation of red wines.
AB  - Two capillary zone electrophoretic (CZE) methods for determination of shikimic
      acid in Chilean red wine were developed and compared with a HPLC method. Both
      electrophoretic methods were carried out by using a reversed electroosmotic flow
      induced by trimethyl(tetradecyl)ammoniumbromide (TTAB) with indirect detection at
      260 nm using p-aminobenzoic acid as a UV-absorbing co-ion or by direct detection
      at 213 nm. In both cases, the separation was carried out in a 50 microm I.D.
      uncoated capillary with an effective length of 48 cm, a negative power supply of
      30 kV, using a buffer based on bis[2-hydroxyethyl]imino
      tris[hydroxymethyl]methane (Bis-Tris), pH 7.0 or 7.5 and hydrodynamic injection.
      The chromatographic separations were carried out on a C-18 reversed phase column
      followed by a sulfonyl-styrene-divinylbenzene (S-DVB) ion exclusion column at 70
      degrees C with H2SO4 0.02 M as isocratic mobile phase and a flow rate of 0.5 mL
      min(-1). The three methods allowed the quantification of shikimic acid with
      quantification limits between 1.0 and 12.0 mg L(-1) and precision between 7.3 and
      10.1%, however, only the concentrations obtained by CZE with direct detection
      were statistically similar to those of HPLC. This parameter was evaluated as
      analytical tool to verify varietal authenticity of red wines. In all cases, the
      Cabernet Sauvignon wines presented higher concentrations of shikimic acid,
      compared with Merlot or Carmenere wines.

PMID- 16106711
TI  - Use of non-aqueous capillary electrophoresis for the quality control of
      commercial saffron samples.
AB  - A non-aqueous capillary electrophoresis (NACE) method for quantifying the seven
      crocin metabolites that are the major biologically active ingredients of saffron
      was developed. Separation is done by using a fused silica capillary filled with a
      12.5 mM H3BO3/37.5 mM sodium tetraborate methanolic solution as background
      electrolyte. The results obtained were compared with the total index "safranal
      value", widely used as a quality measure of saffron products. The comparison
      revealed that the proposed NACE method provides useful information not obtained
      in the safranal value. Infact, samples with a similar safranal value can contain
      crocin metabolites in different concentrations and relative proportions. This new
      method is very useful for quality control in commercial saffron samples.

PMID- 16106712
TI  - Musculoskeletal orofacial pain and other signs and symptoms of temporomandibular
      disorders during pregnancy: a prospective study.
AB  - AIMS: To describe the course of reported musculoskeletal pain in the
      temporomandibular region and other signs and symptoms of temporomandibular
      disorders (TMD) as well as psychological distress over the course of pregnancy
      and 1 year postpartum. METHODS: Women with musculoskeletal orofacial pain (n =
      19) and pain-free comparison subjects (n = 16) in the first trimester of
      pregnancy were selected through records review from the population of a large
      health maintenance organization. Subjects completed a self-administered
      questionnaire assessing pain, depression, and somatic symptoms; provided a sample
      of whole unstimulated saliva; and underwent a standardized clinical examination
      during the third, sixth, and ninth months of pregnancy and 1 year postpartum.
      RESULTS: At baseline (third month of pregnancy), 16 of the 19 patients with
      musculoskeletal orofacial pain met criteria for an RDC/TMD diagnosis. Reported
      musculoskeletal orofacial pain diminished significantly during the second or
      third trimester of pregnancy and increased again postpartum. Measures of
      mandibular opening increased over pregnancy in both cases and comparison subjects
      and remained high postpartum. Depression and somatic symptoms changed little over
      the course of pregnancy but were substantially lowered at 1 year postpartum for
      both groups. As expected, subjects with pain had higher levels of palpation pain,
      diminished mandibular range of motion, and higher levels of psychological
      distress compared to subjects without orofacial pain. CONCLUSION: Musculoskeletal
      orofacial pain and related symptoms appear to improve over the course of
      pregnancy. This improvement occurs in the presence of increased joint laxity and
      is not paralleled by improvements in psychological distress. Thus, it was
      concluded that the improvement in pain is most likely associated with the
      dramatic hormonal changes occurring during pregnancy.

PMID- 16106713
TI  - Neuroendocrine responses to psychological stress in patients with myofascial
      pain.
AB  - AIMS: To investigate the responses of the hypothalamus-pituitary-adrenocortical
      and sympathetic-adrenal-medullary systems to experimentally induced psychological
      stress in patients with myofascial pain. METHODS: To characterize the features of
      these systems, temporal variations in plasma cortisol, adrenaline, and
      noradrenaline concentrations in response to psychological stress were measured in
      20 patients with myofascial pain and in 20 healthy controls. RESULTS: The
      concentrations of plasma cortisol, adrenaline, and noradrenaline in response to
      psychological stress were significantly higher in the pain patients than in the
      healthy controls. Furthermore, although the plasma cortisol, adrenaline, and
      noradrenaline concentrations were significantly increased from the basal levels
      in both groups, the rate of recovery from these levels was significantly slower
      in patients than in healthy controls. CONCLUSION: These results suggest that both
      the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenocortical
      systems are more highly activated in response to psychological stress in patients
      with myofascial pain than in healthy individuals.

PMID- 16106714
TI  - Temporomandibular disorders among smokers and nonsmokers: a longitudinal cohort
      study.
AB  - AIMS: To evaluate whether smoking influences the presence and/or development of
      signs and symptoms of temporomandibular disorders (TMD) among adults. METHODS: A
      random sample of subjects 35, 50, and 65 years of age was drawn from the general
      population and examined with the aid of a questionnaire and a clinical
      examination. Within the sample, smokers were identified based on reported current
      smoking and nonsmokers were matched to the smokers based on age, gender,
      educational level, area of residence, and number of teeth. In total, 268 subjects
      were matched (134 pairs). Six years after the baseline examination, 122 matched
      pairs were re-examined. RESULTS: Mild symptoms of TMD were reported by
      approximately 30% of the sample both at baseline and at the follow-up examination
      6 years later. Pain in the jaws and/or more severe symptoms of TMD were reported
      by approximately 15% on both occasions. No significant differences between
      smokers and nonsmokers were found regarding symptoms of TMD. In both
      examinations, mild signs (dysfunction index I) were found in approximately 40% of
      the sample and moderate to severe signs (dysfunction index II to III) in
      approximately 20%; no statistically significant differences were found between
      smokers and nonsmokers. No significant differences were found between smokers and
      nonsmokers regarding the course of symptoms or signs of TMD during the study
      period. CONCLUSION: Smoking is not a factor related to the presence or
      development of signs and symptoms of TMD.

PMID- 16106715
TI  - Relationship between overbite/overjet and clicking or crepitus of the
      temporomandibular joint.
AB  - AIMS: Since occlusal variables such as overbite and overjet have been thought to
      be associated with temporomandibular disorders (TMD), and joint sounds are some
      of the most prevalent signs of TMD, the aim of this study was to determine
      whether overbite and overjet are risk factors for temporomandibular joint (TMJ)
      sounds. METHODS: A population-based cross-sectional study of 3,033 subjects (age
      range, 10 to 75 years; 53% female) was conducted in Germany. Overbite/overjet,
      reproducible reciprocal clicking (RRC) during open-close jaw movements that did
      not occur in the protrusive jaw position, and joint crepitus were assessed
      according to the Research Diagnostic Criteria for Temporomandibular Disorders
      (RDC/TMD). RESULTS: When age and gender were controlled for, high or low values
      of overbite and overjet were not associated with a greater risk of RRC and
      crepitus as compared to a reference category of a normal overbite and overjet of
      2 to 3 mm (multiple logistic regression; odds ratios 0.7 to 1.3; P > .05 for
      all). CONCLUSION: This study showed that higher or lower overbite or overjet jaw
      relationships, even extreme values, are not risk factors for TMJ sounds as
      assessed by clinical examination.

PMID- 16106716
TI  - Association between masseter muscle activity levels recorded during sleep and
      signs and symptoms of temporomandibular disorders in healthy young adults.
AB  - AIMS: To examine whether any signs and symptoms of temporomandibular disorders
      were significantly associated with masseter muscle activity levels during sleep.
      METHODS: One hundred three healthy adult subjects (age range, 22 to 32 years)
      participated in the study. They were asked to fill out questionnaires, undergo a
      calibrated clinical examination of their jaws and teeth, and perform 6
      consecutive nightly masseter electromyographic (EMG) recordings with a portable
      EMG recording system in their home. The EMG data were considered dependent
      variables, while the questionnaire and examination data were considered
      independent variables. Multiple stepwise linear regression analysis was utilized
      to assess possible associations between these variables. RESULTS: Both gender and
      joint sound scores were significantly related to the duration of EMG activity.
      None of the other independent variables were found to be related to any of the
      muscle activity variables. CONCLUSION: The results suggest that both gender and
      clicking are significantly related to duration of masseter EMG activity during
      sleep.

PMID- 16106717
TI  - A new analyzing method for quantification of abrasion on the Bruxcore device for
      sleep bruxism diagnosis.
AB  - AIMS: To evaluate a newly developed semi-automatic computer-based method to
      analyze the objectivity of the Bruxcore Bruxism-Monitoring Device (BBMD) by
      assessing the interrater reliability. The capability of the BBMD to differentiate
      between sleep bruxers (SB) and healthy controls was also verified by estimating
      the sensitivity, specificity, and predictive values. METHODS: Forty-eight SB and
      21 controls took part in this investigation. After a detailed clinical dental
      examination, each participant received a BBMD to be worn for 5 consecutive
      nights. The BBMDs were then scanned and rated by 2 independent examiners using
      the new method, which counted the abraded area in pixels. Interrater reliability
      was assessed by intraclass correlation coefficient (ICC) analyses. RESULTS: The
      analyses showed a very high interrater reliability of ICC = 0.99, and comparison
      of the mean pixel scores revealed values that were approximately 8 times higher
      for the SB than for the controls. With a selected pixel score cutoff point of
      2900, a sensitivity of 79.2% and a specificity of 95.2% were found. The clinical
      diagnosis was correctly predicted in 97.4% of the SB and 66.7% of the controls.
      CONCLUSION: The results support the assumption that the newly developed analyzing
      method for the assessment of the BBMD is a clinically suitable, objective, and
      applicable method that seems to be able to differentiate between SB and a healthy
      control sample. These data, however, need to be confirmed in further
      investigations using polysomnographic recordings.

PMID- 16106718
TI  - Blink reflexes in patients with atypical odontalgia.
AB  - AIMS: To use the human blink reflex (BR) to explore possible neuropathic pain
      mechanisms in patients with atypical odontalgia (AO). METHODS: In 13 AO patients,
      the BR was elicited using a concentric electrode and recorded bilaterally with
      surface electromyographic (EMG) electrodes on both orbicularis oculi muscles.
      Electrical stimuli were applied to the skin above branches of the V1, V2, and V3
      nerves and to the V branch contralateral to the painful branch. Sensory and pain
      thresholds were determined. The BR examination of the painful V branch was
      repeated during a capsaicin pain-provocation test. The data were analyzed with
      nonparametric statistics. RESULTS: The BR responses (R2 and R3) evoked by
      stimulation of V3 were significantly smaller than the BR responses evoked by
      stimulation of V1 and V2 (P < .004). There were no differences in BR (R2 or R3)
      between the painful and nonpainful sides (P > .569), and the BR (R2 and R3) was
      not significantly modulated by experimental pain (P > .080). The sensory
      thresholds were significantly lower on the painful side compared to the
      nonpainful side (P = .014). The pain thresholds were not different between sides
      (P > .910). CONCLUSION: No major differences between the V nociceptive pathways
      on the right and left sides were found in a relatively small group of AO
      patients. Future studies that compare BRs in AO patients and healthy volunteers
      are needed to provide further knowledge on the pain mechanisms in AO.

PMID- 16106719
TI  - Vanilloid receptor 1 expression in human tooth pulp in relation to caries and
      pain.
AB  - AIMS: To investigate the presence of vanilloid receptor 1 (TRPV1) in human dental
      pulp and to correlate any expression with caries and pain. METHODS: Permanent
      mandibular first molars were collected and categorized as intact or grossly
      carious. Grossly carious teeth were further categorized as carious asymptomatic
      or carious painful samples. Coronal pulps were removed and processed for indirect
      immunofluorescence using antibodies raised against TRPV1 and a neuronal marker,
      either protein gene product 9.5 or alpha-smooth muscle actin, in conjunction with
      Ulex europaeus agglutinin 1 lectin to fully label the pulp vasculature. RESULTS:
      Analysis revealed that TRPV1 labeling was not confined to pulpal nerve fibers.
      TRPV1 was also consistently expressed within pulp microvasculature. Expression of
      neuronal TRPV1 was significantly increased throughout the pulp in grossly carious
      samples (P < .05). No significant differences were found between carious
      asymptomatic and carious painful samples. A significant increase in vascular
      TRPV1 expression was observed in arterioles present in the midcoronal pulp in
      carious painful compared with carious asymptomatic samples (mean area +/- SEM [%]
      of TRPV1 to vascular labeling; 6.48% +/- 4.5% for carious asymptomatic teeth, n =
      9; 31.21% +/- 9.6% for carious painful teeth, n = 9; P = .02). CONCLUSION:
      Expression of TRPV1 in pulpal nerve fibers undergoes marked changes with caries.
      This may be of relevance in the development of pulpal inflammation, but its
      relationship to dental pain is still unclear. However, vascular TRPV1 expression
      does appear to be positively correlated with dental pain, thus providing new
      insights into symptomatic pulpitis.

PMID- 16106720
TI  - Occipital neuralgia secondary to respiratory tract infection.
AB  - Occipital neuralgia is an extracranial pain that may be confused with other
      headaches. It can be attributed to multiple causes. The authors report the case
      of a 55-year-old woman suffering from right occipital neuralgia secondary to
      respiratory tract infection that began 6 days before the pain started. The
      patient suffered from a sharp and burning pain with paroxysms in the right
      occipital region and at the top of the right ear. Sensation was decreased in the
      affected area, and hypersensitivity to touch and cold water was also noted.
      Tinel's sign was present, and local anesthetic block produced pain relief. The
      combination of gabapentin and amitriptyline did not provide significant pain
      relief but led to marked adverse effects. Carbamazepine (300 mg/d) was required
      for pain control. A month later the patient appeared totally pain-free. The
      treatment was continued for 3 months, and the patient remained pain-free over a
      subsequent follow-up period of more than 6 months. Thus, in the case of occipital
      pain, a careful assessment of symptoms and a thorough history are necessary to
      obtain the correct diagnosis and to choose the appropriate treatment plan.

PMID- 16106721
TI  - [Treatment of pulmonary hypertension in COPD: is there hope for the better?].
AB  - The aim of this study is to prove for a well tolerated medication (clinical and
      financial) a supplementary effect in improvement prognosis of patients with
      pulmonary hypertension secondary to COPD, already treated with classical
      pneumology drugs. Three pts. groups were selected: the first received only
      classical pneumology treatment, the second with supplementary therapy by IECA and
      Ca-blockers, the third with supplementary therapy with IECA and nebivolol; the
      follow-up protocol included clinical and paraclinical status (blood gases,
      spirometry, ECG, echocardiography, 6 minute walk test) over 3 months. Clinical
      and paraclinical evolution of the pts. in group 2 and group 3 was significantly
      better that in pts from group 1. We conclude that addition of IECA + Ca
      blocker/IECA + nebivolol therapy at classical pneumology therapy result in a
      better evolution in pts. with pulmonary hypertension secondary to COPD.

PMID- 16106722
TI  - [Left cardiac dysfunction in COPD].
AB  - The study of evaluation and rehabilitation of COPD patient (SERBOC) started in
      January 2004 in the 6th Medical Clinic of the Iasi Rehabilitation Hospital. One
      of its goals is to evaluate the left cardiac morphology and function in the
      chronic obstructive pulmonary disease. The inn-patients have been complexly
      approached by physical examination, chest X-ray, rest electrocardiogram,
      echocardiography and Holter monitoring. The stage result is that physical
      examination, chest X-ray and rest electrocardiogram fails in offering
      satisfactory information regarding left cardiac dysfunction; it is necessary to
      add Holter monitoring and especially echocardiography. The conventional and
      Doppler echocardiography performed in our clinic allowed the possibility to
      identify diastolic dysfunction in all 9 patients and systolic dysfunction in 7 of
      them.

PMID- 16106723
TI  - [Cost analysis in patients admitted with COPD in 2002].
AB  - The aim of the study was to assess the costs of hospital admission for COPD
      patients in a high level unit ("Marius Nasta" Institute of Pulmonology) in order
      to appreciate the financial burden of the disease. We analyzed retrospectively
      the medical charts of patients admitted between January and September 2002. 181
      charts were included. We extracted data regarding the patient (age, sex, smoking
      habits, income), disease (duration, severity) and hospital admittance (number of
      days, tests performed, medication received). Data were processed in EpiInfo 6.
      RESULTS: mean duration of admittance was 17, 18 days. Mean cost of admittance was
      25,448,348 lei (727 Euro), divided in: mean costs of the lab tests - 5,936,812
      lei (170 Euro), mean cost of medication--4,428,000 lei (126 Euro), with obvious
      dominance of COPD medication: 4,310,022 lei; mean cost of hospital stay
      (including hotel, food and personnel expenses) was 15,120,094 lei (432 Euro).
      COPD severity was judged on the spirometry at discharge. Mean FEV1 was 45.66% of
      predicted value. According to GOLD, 10 pts (5.52%) were in stage I, 44 pts
      (24.3%) in stage II, 69 (38.12%) in stage III and 58 pts (32.03%) in stage IV.
      Costs per patient were similar for stages I, II and III and significantly higher
      for stage IV CONCLUSIONS: admitted COPD patients are in severe stages, with a
      long duration of admittance. Overall costs are much smaller than in Europe, more
      than half of these costs are due to hospital stay.

PMID- 16106724
TI  - [Community acquired pneumonia--management and therapeutic approach].
AB  - Risk factors and patient stratification are important parameters in the
      assessment and management of patients with community-acquired pneumonia. In
      accordance to several guidelines, stratification of patients by various factors
      (severity of disease, presence of co-morbidities, modifying factors) are helpful
      in specific management decision such as site of care, extent of diagnostic
      testing and empirical antimicrobial therapy.

PMID- 16106725
TI  - [Ultrasound guided diagnostic procedures in the thorax].
AB  - Fluid in the pleural cavity, parenchyma masses and consolidation provide
      excellent sonographic windows for scanning. Ultrasound has proven extremely
      useful in directing interventional procedures in the pleural space, pulmonary
      parenchyma and mediastinum. Ultrasound offers a number of advantages over other
      imaging methods, the most important being the capability to monitor continuously
      the interventional procedures, thus assuring maximum safety and benefit. We will
      discuss the indications, technique, performances and complications of ultrasound
      guided thoracic puncture in the pleural space, pulmonary parenchyma and
      mediastinum.

PMID- 16106726
TI  - [Non-invasive markers in evaluating inflammation and remodeling in lung diseases.
      1. Induced sputum].
AB  - Development of non-invasive markers of airway inflammation and remodelling is
      needed for diagnosis and monitoring of respiratory diseases, like asthma, COPD
      and interstitial lung diseases. This review is the first in a series evaluating
      the actual status of this process and is dedicated to induced sputum. We describe
      the methods of sputum induction, with special reference to efficiency and safety,
      especially in asthma patient. Methods of sputum processing are reviewed according
      to the end result: differential cell count, soluble markers assays, and also
      immunocytochemistry and in situ hybridisation. Finally we review the use of
      induced sputum in the evaluation of inflammation and remodelling in asthma and
      COPD and also in the evaluation of inflammation in chronic cough and interstitial
      lung diseases.

PMID- 16106727
TI  - [Tiotropium--the "surgical" drug].

PMID- 16106728
TI  - [Thromboembolic chronic pulmonary hypertension--a fake primary pulmonary
      hypertension--case report].
AB  - Chronic pulmonary hypertension (CPHT) is on the third place of causes leading to
      cardiovascular morbidity and mortality in patients over fifty. Two of the rare
      causes of CPHT (< or = 7%) are: chronic thromboembolic hypertension and primary
      one; these two diseases resemble in many situations and, consequently, the
      diagnosis is frequently difficult (especially when risk factors for recurrent
      pulmonary thromboembolism are not present). Our case presentation is just such a
      situation; only pulmonary perfusion scintigraphy allowed us to make the right
      diagnosis--chronic thromboembolic pulmonary hypertension--in an "apparently
      clear" primary pulmonary hypertension.

PMID- 16106729
TI  - [Invasive procedures in positive diagnosis of solitary pulmonary nodule].

PMID- 16106730
TI  - [Air-liquid thoracic image].

PMID- 16106731
TI  - [November 18, 2004--National Non-smoking Day].

PMID- 16106732
TI  - [The first public accord of world health has been achieved. Convention on tobacco
      control becomes an international law against lobbying by the giants of the
      tobacco industry].

PMID- 16106733
TI  - [Effectiveness of antireflux therapy in asthmatic children with gastroesophageal
      reflux disease].
AB  - There is an increased interest within literature regarding the relationship
      between gastro-esophageal reflux disease and asthma. The study was performed to
      assess the efficiency of antireflux therapy in asthmatic children. In a group of
      asthmatic children (n = 34, 22 male, age range: 2, 5-17 years) the pulmonary
      function tests were made by means of spirometry in those patients in which reflux
      disease was diagnosed by means of 24h esophageal pH-monitoring and upper
      digestive endoscopy. All these patients were reevaluated by means of spirometry 3
      months after the antireflux therapy with ranitidine and cisapride added to
      antiasthmatic therapy. Three months later the results showed a significant
      decrease in frequency of asthma exacerbations from 3.18 +/- 4.86 to 0.45 +/- 0.80
      (p = 0.016). There is also a significant increase of FEV1 (p = 0.04) and of
      FEV1/FVC (p = 0.018) in asthmatic patients with reflux disease and a positive
      symptomatic index, and of FEV1/FVC (p = 0.002) in all asthmatic children with
      abnormal gastro-esophageal reflux respectively. In conclusion, by adding
      antireflux therapy in asthmatic children there is a significant improvement in
      clinical and some of functional parameters.

PMID- 16106734
TI  - [Proliferation and differentiation of neural stem cells within the subependymal
      layer of lateral brain ventricles in response to the neurodegenerative process in
      the striatum].
AB  - It is known that the subependymal layer (SEL) of the lateral brain ventricles'
      wall is a source of neural stem cells (NSCs) of adult mammalian brain including
      the human brain. The NSCs in relation to the striatum differentiate only into
      glial phenotype. Therefore we focused on proliferative activity of NSCs and
      precursors in the SEL and on the course of their differentiation into the
      astrocytes in reaction to the neurodegenerative process in the striatum like in
      Huntington's disease. Increased gliogenesis, differentiation of newly generated
      cells and their ability to migrate into the striatum were evaluated in two groups
      of the rats surviving 1 and 3 months after the application of the neurotoxic
      (ibotenic) acid into the striatum. For evaluation of the proliferative activity
      we compared the results obtained using two proliferative markers-
      Bromodeoxyuridine (BrdU) and Ki-67. Characterization of newly generated cells and
      of their differentiation was based on the detection using the following
      antibodies: Nestin (a marker for NSCs and precursors), GFAP (detection of
      astrocytes), also the double-staining method with BrdU and GFAP.

PMID- 16106735
TI  - [Method of polymerase chain reaction in toxoplasmosis diagnosis].
AB  - Since introduction of polymerase chain reaction for the detection of DNA
      Toxoplasma gondii 398 biological samples from 301 patients were examined from
      2000 to 2003. Positive finding of toxoplasmosis DNA we noted in 23 cases.
      Polymerase chain reaction enables exact and fast diagnosis of the actual
      parasitemia Toxoplasma gondii, which is important especially in the pregnant
      patients, new-born with suspicion on congenital toxoplasmosis and in the patients
      with immunosupression.

PMID- 16106736
TI  - [The effect of polycyclic aromatic hydrocarbons to bone marrow].
AB  - Polycyclic aromatic hydrocarbons (PAH) represent a group of ubiquitous
      environmental pollutants. Their toxic effects are demonstrated mainly in tissues
      with high proliferation. The direct distribution of PAH in non-metabolized form
      to bone marrow and their biotransformation at this site to the toxic metabolites
      is necessary for demonstration of their toxic effect here. CYP1B1 that is
      constitutive expressed by stromal cells plays probably the main role in
      biotransformation of PAH in bone marrow. Reactions of toxic metabolites,
      development of oxidative stress and interference with intracellular calcium are
      ranged between the most important mechanisms of structural and functional changes
      of bone marrow after exposure to PAH. Pathological induction of apoptosis and
      malignant transformation of stem cells represent the concrete forms of bone
      marrow damage, caused by exposure to PAH. The bone marrow constitutes the central
      organ of hematopoiesis and the sites of production of cells of immune system. Its
      damage can bring therefore crucial health consequences for the whole organism.

PMID- 16106737
TI  - [Genetic aspects of idiopatic inflammatory bowel disease].
AB  - Idiopatic bowel disease, Crohn' s disease and ulcerative colitis, are grave
      illneses of gastrointestinal tract. Mechanisms that lead to the development of
      inflammatory bowel disease are not well understood, but genetic play an important
      role. The main arguments gathered are ethnic/racial difference in disease
      frequency, positive family history, increased concordance rate in monozygotic
      twins relative to dizygotic and genes associated with Crohn's disease and
      ulcerative colitis. The enviromental factors play also an important role.

PMID- 16106738
TI  - [The influence of fertility and idiopatic bowel disease: a summary].
AB  - Idiopatic bowel diseases parallels the female reproductive period, therefore it's
      been examined the influence of Crohn's disease and ulcerative colitis on
      pregnancy and of pregnancy on disease itself. There are many questions about the
      effects of the disease on fertility, course of pregnancy, influence of fetus and
      other factors related to puerperium. Many factors of the disease, pharmacological
      therapy and surgical interventions are associated with the disease. Psychological
      aspects are also included.

PMID- 16106739
TI  - [Occupational asthma: current state of the problem].
AB  - Occupational asthma is a disease with serious medical, social and economical
      consequences. Most patients have to change their jobs and very often they lose
      their professional qualification. This article gives a current review of the
      problems of occupational bronchial asthma and allergic rhinitis in the region of
      Eastern Bohemia. The results obtained are compared with the situation in the
      whole Czech Republic and in the world. The number of new cases of occupational
      asthma and allergic rhinitis discovered in the contact area of the Department of
      Occupational Medicine at the University Hospital in Hradec Kralove fluctuates
      around 15-20 cases per year, and 80-100 new cases are reported in the whole
      republic. The rate of occupational asthma and occupational allergic rhinitis of
      the total asthma and rhinitis incidence in the Czech population fluctuates
      between 5-15%. Regarding the number of affected employees, flour is considered
      the most important allergen. Other important noxas include agricultural
      allergens, textile dust, diisocyanates and disinfectious preparations. The
      importance of the alergogenius effect of natural rubber latex and diisocyanates
      has increased in occupational medicine mainly in the last 20 years. Regarding
      latex, its harmful effect has been especially demonstrated in health providers
      who wear protective latex gloves, which results not only in contact eczema
      dermatitis, but also in bronchial asthma and allergic rhinitis. Diisocyanates,
      highly reactive and aggressive substances, originate during polyurethane
      production which has a wide industrial application (production of polyurethane
      foam and rubber, paints, adhesives, injected substances, glues, varnishes etc.).
      The incidence of occupational asthma diseases in workers exposed to diisocyanates
      is high. Typically, a development of the disease begins after a short time
      exposure. In this thesis, a diagnostic method in suspected occupational allergic
      disease of the airways is suggested and possibilities for the application of
      particular diagnostic methods are given with emphasis on their advantages and
      limitations and the necessity to determine a proper diagnostic method for the
      individual patient. In searching for a particular cause of the occupational
      disease a significant benefit is the determination of a wide range of specific Ig
      E class serum antigens, in case IgG and standardization of the method provoke
      tests for its practical application.

PMID- 16106740
TI  - [Diseases caused by asbestos dust and the trend of their development in exposed
      workers in 1951-2003].
AB  - The paper summarizes the principal information on the properties and effects of
      asbestos and a survey of diseases which can be recognized in the Czech Republic
      as occupational diseases according to the List of Occupational Diseases
      (Government Order 290/1995 Coll.). The paper lists possible diagnostic means and
      criteria for evaluation and presents a survey of developmental trends of the
      disease in exposed workers of the plant under study. In the period of years 1951
      2003, 87 cases of occupational diseases were reported. The first asbestosis
      occurred in 1955, the first lung cancer in a patient with a previously reported
      asbestosis in 1962, the first pleural mesothelioma in 1976, the first asbestosis
      of the lung with concurrent lung cancer in 1981, and the first pleural hyalinosis
      in 1999. A very serious fact is that 56, i.e. 64.4% of diseases, particularly
      lung cancer and mesothelioma, were diagnosed after the termination of working in
      risk and many years of latency. A long-term folow-up of workers, even of those
      with a short exposure, is therefore necessary.

PMID- 16106741
TI  - [Our statistical programs in Excel].
AB  - We prefer to use a spreadsheet program when teaching statistics. We have written
      several programs to cover the methods students use. The input data are typed in
      the spreadsheet MS Excel, we mark the data, and the program creates an output
      table. The outputs are both in Czech and English, they contain the basic results
      useful for students, various alternatives, test criteria, acceptance regions, and
      p-values. Since the programs are user-friendly, they make it easier on students.

PMID- 16106742
TI  - [Assessment of autonomous reactivity at stuttering treated in bronchodilatation
      therapy].
AB  - By the measurement of autonomous reactivity according to the variability of heart
      frequency we get a picture that describes the activity of autonomous nervous
      system and stuttering at bronchodilatal therapy.

PMID- 16106743
TI  - [Multimedia teaching software in university education].
AB  - This article is aimed at developing of multimedia teaching programs. Authoring
      tool Authorware Professional for Windows is briefly described as a suited system
      for the developing of didactic applications. Author presents own application
      based on Authorware--Biophysics of perception of sound and light. At the end are
      also disscused benefits of multimedia teaching tools.

PMID- 16106744
TI  - [MIAPS--programme system for order estimation of mutual similarity/dissimilarity
      of proteins behavior in time].
AB  - Statistical order estimation of mutual similarity/dissimilarity of proteins'
      behavior in time is the main purpose of the programme system MIAPS. Comparing
      with Correspondence Analysis (CA) method, mostly used so far, is simultaneously
      performed. Time series of 2-DE maps are requested as the data. MIAPS is available
      on http://www.lfhk.cuni.cz/knizekj/ and
      http://www.utia.cas.cz/user_data/sindelar/miaps.htm.

PMID- 16106745
TI  - [Free sources for medical informatics teaching].
AB  - Important worldwide websites offering medical informatics have been searched
      through to find freely available web-based sources for teaching of medical
      informatics at faculties of medicine. The conclusion suggests that a complex
      system for teaching of the whole field of study does not exist. However, a
      sufficient offer of specialized articles, model programmes and presentations is
      available, which can be used for teaching. The author lists a brief
      characterization of the found sources and the programmes he uses. This computer
      aided research is only rough. A more precisely defined searching strategy can
      help find other sources of specialized subjects useful for medical informatics.

PMID- 16106746
TI  - [Application of electronic signature for electronic medical documents].
AB  - This work deals with analysis of technical and legal aspects of qualified
      electronic signature implementation in the area of electronic medical information
      systems with respect to real usability of such a signature as an equivalent to a
      manual signature on paper medical documents.

PMID- 16106747
TI  - [Intensity-modulated radiotherapy in the treatment of thyroid cancer].
AB  - The main problem of the conventional radiotherapy in postoperative or curative
      irradiation in thyroid cancer is to achieve a sufficient dose in the planning
      target volume with acceptable dose distribution homogeneity and at the same time
      not to exceed tolerance doses in the organs of risk. Our study presents the
      advantages of intensity-modulated radiotherapy over conventional radiotherapy on
      an example of dosimetric comparisons of isodose plans of three patients treated
      at our department. The intensity-modulated radiotherapy in thyroid cancer offers
      an improvement of dose homogeneity and better sparing of organs at risk (spinal
      cord and lungs). Furthermore, dose escalation is feasible in the whole initial
      planning target volume up to 60 Gy with a simultaneous sparing of healthy tissues
      and organs at risk.

PMID- 16106748
TI  - Detection and normalization of biases present in spotted cDNA microarray data: a
      composite method addressing dye, intensity-dependent, spatially-dependent, and
      print-order biases.
AB  - Microarrays are often used to identify target genes that trigger specific
      diseases, to elucidate the mechanisms of drug effects, and to check SNPs.
      However, data from microarray experiments are well known to contain biases
      resulting from the experimental protocols. Therefore, in order to elucidate
      biological knowledge from the data, systematic biases arising from their
      protocols must be removed prior to any data analysis. To remove these biases,
      many normalization methods are used by researchers. However, not all biases are
      eliminated from the microarray data because not all types of errors from
      experimental protocols are known. In this paper, we report an effective way of
      removing various types of biases by treating each microarray dataset
      independently to detect biases present in the dataset. After the biases contained
      in each dataset were identified, a combination of normalization methods
      specifically made for each dataset was applied to remove biases one at a time.

PMID- 16106749
TI  - The WRKY family of transcription factors in rice and Arabidopsis and their
      origins.
AB  - WRKY transcription factors, originally isolated from plants contain one or two
      conserved WRKY domains, about 60 amino acid residues with the WRKYGQK sequence
      followed by a C2H2 or C2HC zinc finger motif. Evidence is accumulating to suggest
      that the WRKY proteins play significant roles in responses to biotic and abiotic
      stresses, and in development. In this research, we identified 102 putative WRKY
      genes from the rice genome and compared them with those from Arabidopsis. The
      WRKY genes from rice and Arabidopsis were divided into three groups with several
      subgroups on the basis of phylogenies and the basic structure of the WRKY domains
      (WDs). The phylogenetic trees generated from the WDs and the genes indicate that
      the WRKY gene family arose during evolution through duplication and that the
      dramatic amplification of rice WRKY genes in group III is due to tandem and
      segmental gene duplication compared with those of Arabidopsis. The result
      suggests that some of the rice WRKY genes in group III are evolutionarily more
      active than those in Arabidopsis, and may have specific roles in monocotyledonous
      plants. Further, it was possible to identify the presence of WRKY-like genes in
      protists (Giardia lamblia and Dictyostelium discoideum) and green algae
      Chlamydomonas reinhardtii through database research, demonstrating the ancient
      origin of the gene family. The results obtained by alignments of the WDs from
      different species and other analysis imply that domain gain and loss is a
      divergent force for expansion of the WRKY gene family, and that a rapid
      amplification of the WRKY genes predate the divergence of monocots and dicots. On
      the basis of these results, we believe that genes encoding a single WD may have
      been derived from the C-terminal WD of the genes harboring two WDs. The conserved
      intron splicing positions in the WDs of higher plants offer clues about WRKY gene
      evolution, annotation, and classification.

PMID- 16106750
TI  - Transcription profiling of signal transduction-related genes in sugarcane
      tissues.
AB  - A collection of 237,954 sugarcane ESTs was examined in search of signal
      transduction genes. Over 3500 components involved in several aspects of signal
      transduction, transcription, development, cell cycle, stress responses and
      pathogen interaction were compiled into the Sugarcane Signal Transduction
      (SUCAST) Catalogue. Sequence comparisons and protein domain analysis revealed 477
      receptors, 510 protein kinases, 107 protein phosphatases, 75 small GTPases, 17 G
      proteins, 114 calcium and inositol metabolism proteins, and over 600
      transcription factors. The elements were distributed into 29 main categories
      subdivided into 409 sub-categories. Genes with no matches in the public databases
      and of unknown function were also catalogued. A cDNA microarray was constructed
      to profile individual variation of plants cultivated in the field and transcript
      abundance in six plant organs (flowers, roots, leaves, lateral buds, and 1st and
      4th internodes). From 1280 distinct elements analyzed, 217 (17%) presented
      differential expression in two biological samples of at least one of the tissues
      tested. A total of 153 genes (12%) presented highly similar expression levels in
      all tissues. A virtual profile matrix was constructed and the expression profiles
      were validated by real-time PCR. The expression data presented can aid in
      assigning function for the sugarcane genes and be useful for promoter
      characterization of this and other economically important grasses.

PMID- 16106751
TI  - Characterization of the structure and expression of mouse Itpa gene and its
      related sequences in the mouse genome.
AB  - In the mouse genome, we found one processed Itpa gene-like sequence and two
      processed Itpa pseudogenes as well as the Itpa gene itself with introns, located
      on chromosome 2F3, which was isolated by a retro-recombination method. We also
      identified three types (A, B, C) of Itpa transcripts in mouse tissues. The
      processed Itpa gene-like sequence located on chromosome 2E1 has a complete open
      reading frame for exactly the same polypeptide as ITPA encoded by the type A
      transcript, with a polyadenylation signal. However, no transcribed sequence
      derived from the Itpa gene-like sequence was detectable in any of the mouse
      tissues examined, thus naming the sequence as Itpa processed pseudogene alpha.
      The type A Itpa mRNA, which was expressed in all mouse tissues examined, only
      encodes mouse ITPA polypeptide consisting of 198 amino acid residues with a
      capacity to hydrolyze dITP into dIMP. Itpa mRNA was detected in all tissues
      examined, and its expression is especially high in the testis, brain, and thymus.
      ITPA protein was mostly detected in the cytoplasm, to a lesser extent in the
      nuclei of neurons in the brain, and also those of hepatocytes, epithelial cells
      lining the bile duct, and endothelial cells lining the portal vein in the liver.

PMID- 16106752
TI  - Vector-capping: a simple method for preparing a high-quality full-length cDNA
      library.
AB  - Full-length cDNAs play an essential role in identifying genes and determining
      their promoter regions. Here we describe a simple method for constructing a full
      length cDNA library, which has the following advantages: (i) it consists of only
      three steps including direct ligation between a vector and a cDNA strand using T4
      RNA ligase, (ii) it contains neither a PCR process generating mutations nor
      restriction enzyme treatment causing truncation of cDNA, (iii) the intactness of
      cDNA is assured due to the presence of an additional dGMP at its 5' end, (iv)
      approximately 95% of cDNA clones are full-length when cultured cells or fresh
      tissues are used, (v) several micrograms of total RNA without mRNA purification
      is sufficient for preparation of a library containing >10(5) independent clones,
      and (vi) a long-sized full-length cDNA up to 9.5 kbp can be cloned. This method
      will accelerate comprehensive gene analysis in a variety of eukaryotes.

PMID- 16106753
TI  - A complete set of Escherichia coli open reading frames in mobile plasmids
      facilitating genetic studies.
AB  - To facilitate genetic studies of Escherichia coli, we constructed a complete set
      of mobile plasmid clones of intact open reading frames (ORFs). Their expression
      is strictly controlled by Ptac / lacI(q). The plasmids carrying each ORF were
      introduced into an F+ recA strain and stored in 96-well microtiter plates. In
      this way, 96 clones can be transferred simultaneously to F- bacteria using the
      conjugative system. This provides a convenient procedure for systematic
      identification of ORFs that suppress or complement mutations. We created two
      types of clone sets: the original set contained individual clones in 45
      microtiter plates, and a second set contained pools of 48 clones stored in a
      single microtiter plate. Using these clone sets, we have identified 403 genes
      that can correct in trans the temperature-sensitive defect of cell division
      mutants, which would suggest multiple global regulators for bacterial cell
      division.

PMID- 16106754
TI  - Lotus burttii takes a position of the third corner in the lotus molecular
      genetics triangle.
AB  - In order to consolidate molecular genetic system in Lotus japonicus and to
      further access the biological diversity in Lotea, we introduce here Lotus burttii
      B-303 derived from West Pakistan as the third crossing partner of the Gifu
      ecotype (B-129-S9) for a genetic analysis. L. burttii is a relatively small and
      early flowering plant with non-shattering behavior. The general chromosome
      morphology is very similar to Gifu, and fluorescence in situ hybridization (FISH)
      analysis revealed that the short arm of chromosome 1 in L. burttii is comparable
      to that of Gifu, indicating that the translocation event involving chromosomes 1
      and 2, which was observed in L. japonicus Miyakojima MG-20, is not present in L.
      burttii. In addition L. burttii has a higher level of DNA polymorphism compared
      to Gifu and MG-20 enabling design of codominant markers such as SSR, CAPS and
      dCAPS. Using an F2 population from a cross between Gifu and L. burttii,
      codominant makers that co-segregated at the translocation site could be expanded.
      In order to normalize the genetic background, L. burttii was inbred for nine
      generations and the germplasm L. burttii B-303-S9 was established.

PMID- 16106755
TI  - [Isolation and therapeutic use of human stem cells].
AB  - Nowadays, adult stem cells are the main target of biological research. Stem cell
      specific markers allow the extraction in enough quantity and high purity of
      multipotent cells from organic tissues, and their usage instead of the ethically
      reprehensible embryonal stem cells in experimental therapeutic purposes is also
      possible. The key point in the development of a new, stem-cell based therapeutic
      methodology is the determination of stem cell specific cell surface or
      cytoplasmatic antigens that makes reliable stem cell identification possible.
      Bone marrow derived multipotent stem cells can already be suitably identified,
      and other, more or less organic tissue-derived stem cell specific markers are
      also available. The first therapeutic interventions have been already done in
      diseases such as myocardial infarction or diabetes mellitus, and led to promising
      results.

PMID- 16106756
TI  - [Diabetes mellitus in children].
AB  - The review is covering different forms of diabetes mellitus occurring in children
      and adolescents. Main characteristics of childhood diabetes are based on the
      continuous changes in growth and development of children. The review is focusing
      on the diagnostics, epidemiology, etiopathogenesis and natural course of type 1
      diabetes, the dominant form in the pediatric age group. Insulin treatment,
      nutritional management and education, including age related special problems are
      covered. Due to space limitations, acute and late complications, as well as
      possible prevention of type 1 diabetes are shortly mentioned. Beside type 1
      diabetes, other forms of carbohydrate intolerance occurring in children are also
      also included. Among those, special emphasis is put on type 2 diabetes, due to
      its increasing incidence in children and adolescents parallel to the increased
      prevalence of childhood obesity.

PMID- 16106757
TI  - [Ghrelin--a hormone with multiple functions].
AB  - The growth hormone secretagogue ghrelin is in the centre of interest since its
      discovery in 1999. It stimulates growth hormone, corticotropic hormone and
      prolactin secretion, but also plays an important role in the regulation of
      appetite, carbohydrate- and lipid metabolism and possibly on gastric acid
      secretion, gastric motility, heart function and as well as immune functions and
      cell proliferation. Ghrelin was originally identified from the stomach but it is
      also present in all tissue among others in: hypothalamus, pituitary, pancreas,
      lung, immune cells, placenta, ovary, testis, kidney and in different tumours
      including pituitary adenoma, neuroendocrine tumours, thyroid carcinomas,
      endocrine tumours of the pancreas and lung. The gene structure and its receptor
      are similar to motilin, they are both synthesized in the upper gastrointestinal
      tract and both have prokinetic activity on gut motility. The ghrelin receptor
      (growth hormone secretagogue receptor) is a member of G protein-coupled seven
      transmembrane domain receptor. The receptor is localised in the central nervous
      system, kidney, thyroid, pancreas, myocardium and spleen. Starvation and low body
      mass index decrease, while food intake, hyperglycaemia, elevated insulin levels
      and high body mass index increase the endogenous ghrelin levels. Although we know
      much about the ghrelin, number of questions remain unanswered, such as the
      effects of the locally-produced ghrelin or its role in the cell metabolism.

PMID- 16106758
TI  - [Thoughts about philosophy of medicine--today].

PMID- 16106759
TI  - [Nephrotic syndrome in Hodgkin's disease].
AB  - The authors are presenting a rare paraneoplastic syndrome in Hodgkin's disease.
      Young female patient presented with symptoms of nephrotic syndrome. Renal biopsy
      showed mesangiocapillary glomerulonephritis. Remission was achieved with combined
      therapy. Four months later, when the nephrosis syndrome relapsed, Hodgkin's
      disease was diagnosed (nodular sclerosing subtype). Hodgkin's disease was staged
      as III/BS. Polychemotherapy resulted complete remission of both Hodgkin's disease
      and nephrotic syndrome. Causes of nephrotic syndrome in Hodgkin's disease can
      include renal vein thrombosis, amyloidosis or paraneoplastic syndrome. Nephrotic
      syndrome in Hodgkin's disease may relate to dysfunction of T-cells or altered
      cytokine balance, but the exact pathogenesis is not known. This case attracts
      attention that a rare cause of nephrotic syndrome can be Hodgkin's disease.

PMID- 16106760
TI  - Why are they boxing us in like this?

PMID- 16106761
TI  - Do elderly persons' concerns for family burden influence their preferences for
      future participation in dementia research?

PMID- 16106762
TI  - The politics of care: dementia and accounting versus caring for mortification.

PMID- 16106763
TI  - Deciding for others at the end of life: storytelling and moral agency.

PMID- 16106764
TI  - Emancipation, capacity, and the difference between law and ethics.

PMID- 16106765
TI  - Proactive bioethics screening: a prelude to bioethics consultation.

PMID- 16106766
TI  - Readability level of HIPAA notices of privacy practices used by physical
      rehabilitation centers.

PMID- 16106767
TI  - Physicians, medical ethics, and capital punishment.

PMID- 16106768
TI  - Saying "good-bye": ethical issues in the stewardship of bed spaces.

PMID- 16106769
TI  - A response to Shalowitz and Emanuel.

PMID- 16106770
TI  - The Western Galilee experience: reducing infant mortality in the Arab population.
AB  - Until the end of the 1980s almost no intensive intervention plan was applied to
      narrow the vast gap (over 100%) in infant mortality between Jews and Arabs in the
      Western Galilee region of Israel. A special committee appointed by the Ministry
      of Health instituted measures to reduce the gap, including monitoring mortality
      rates by establishing an online and real-time computerized information system to
      analyze the information without delay. Based on the epidemiologic findings, an
      intervention program was implemented, using health education to reduce mortality
      due to seasonal infections--gastroenteritis in summer and upper respiratory and
      hyperthermia in winter. Within 1 year these infections had abated, resulting in
      significantly reduced mortality. The next step was the development of an
      ultrasound preventive campaign using sophisticated sonography to screen pregnant
      women in risk groups for lethal congenital defects and convincing them to
      discontinue the pregnancy. These two measures reduced infant mortality
      dramatically. The campaign has been widened to the entire northern district and
      is presently addressing, as a primary prevention, the traditionally difficult
      problem of consanguineous marriages--the major cause of congenital defects in the
      Arab population.

PMID- 16106771
TI  - Teledermatology: quality assessment by user satisfaction and clinical efficiency.
AB  - BACKGROUND: The Israel Defense Forces implemented a pilot teledermatology service
      in primary clinics. OBJECTIVES: To assess user satisfaction and clinical short
      term effectiveness of a computerized store and forward teledermatology service in
      urban and rural units. METHODS: A multi-center prospective uncontrolled cohort
      pilot trial was conducted for a period of 6 months. Primary care physicians
      referred patients to a board-certified dermatologist using text email accompanied
      by digital photographs. Diagnosis, therapy and management were sent back to the
      referring PCP. Patients were asked to evaluate the level of the CSAFTD service,
      effect of the service on accessibility to dermatologists, respect for privacy,
      availability of drugs, health improvement and overall satisfaction. PCPs assessed
      the quality of the teledermatology consultations they received, the contribution
      to their knowledge, and their overall satisfaction. RESULTS: Tele-diagnosis alone
      was possible for 95% (n=413) of 435 CSAFTD referrals; 22% (n=95) of referrals
      also required face-to-face consultation, Satisfaction with CSAFTD was high among
      patients in both rural and urban clinics, with significantly higher scores in
      rural units. Rural patients rated the level of service, accessibility and overall
      satisfaction higher than did urban patients. PCPs were satisfied with the quality
      of the service and its contribution to their knowledge. Rural physicians rated
      level of service and overall satisfaction higher than did urban physicians. Tele
      referrals were completed more efficiently than referral for face-to-face
      appointments. CONCLUSIONS: CSAFTD provided efficient, high quality medical
      service to rural and urban military clinics in the IDF.

PMID- 16106772
TI  - Ureteral stents: morbidity and impact on quality of life.
AB  - BACKGROUND: Stents offer a simple and effective drainage method for the upper
      urinary tract. However, ureteral stents are associated with frequent side
      effects, including irritative voiding symptoms and hematuria. OBJECTIVES: To
      determine the side effects associated with ureteral stents and their impact on
      sexual function and quality of life. METHODS: Symptom questionnaires were
      administered to 135 consecutive patients with unilateral ureteral stents. The
      questionnaire addressed irritative voiding symptoms, flank pain, hematuria,
      fever, loss of labor days, anxiety, sleep impairment, decreased libido, erectile
      dysfunction, dyspareunia, painful ejaculation, and a subjective overall impact on
      quality of life. The items were graded from 1 (minimal or no symptoms) to 5
      (maximal symptoms). The patients were seen and questionnaires filled at 2 weekly
      intervals following stent insertion until stent extraction. Following removal of
      the stent, stent patency, impaction and migration rates were determined.
      Admissions to hospital and ancillary procedures to retreive stents were noted.
      RESULTS: The findings presented refer to questionnaire items scoring 3 or more.
      Dysuria, urinary frequency and urgency were reported by 40%, 50% and 55% of the
      patients, respectively. Flank pain, gross hematuria or fever was reported by 32%,
      42% and 15% respectively. Among working patients, 45% lost at least 2 labor days
      during the first 14 days, and 32% were still absent from work by day 30. A total
      of 435 labor days were lost in the first month. Anxiety and sleep disturbance
      were reported by 24% and 20% respectively, and 45% of patients reported
      impairment in their quality of life. Decreased libido was reported by 45%, and
      sexual dysfunction by 42% of men and 86% of women. Stent removal necessitated
      ureteroscpoy in 14 patients (10.5%), due to upward migration in 11 (8.2%) and
      incrustration and impaction in 3. Spontaneous stent expulsion occurred in one
      patient. Forty-six stents (34%) were obstructed at the time of removal.
      Obstructed stents were associated with a longer mean dwell time as compared to
      the whole population, 75 versus 62 days respectively (P = 0.04). CONCLUSIONS:
      Ureteral stents are associated with frequent side effects and significant impact
      on patient quality of life. Our findings should be considered when deciding on
      ureteral stent insertion and dwell time.

PMID- 16106773
TI  - Visibility of normal thoracic anatomic landmarks on storage phosphor digital
      radiography versus conventional radiography.
AB  - BACKGROUND: Chest radiography is still the most frequently performed radiologic
      imaging study. Digital radiography is gradually replacing the conventional
      systems. OBJECTIVES: To compare the subjective visibility of normal anatomic
      landmarks in the chest on storage phosphor-based digital radiographs versus
      conventional screen-film radiographs. METHODS: Digital phosphor-based and screen
      film posteroanterior chest radiographs were obtained during 1 year in 140
      asymptomatic patients without any known pulmonary disease (119 men, 21 women;
      mean age 52.1 years, range 23-86). Both sets of films were independently compared
      by two experienced radiologists in different sessions. The visibility of each of
      the following anatomic landmarks was graded from 1 to 3: pulmonary fissures,
      carina, bronchi to left upper lobe, right upper lobe and left lower lobe,
      bronchus intermedius, anterior and posterior junctional lines, and vessels behind
      the heart and diaphragm. Additionally, subjective general quality impression of
      each radiograph was graded similarly. Statistical analyses were performed using
      the chi-square test. A P value less than 0.05 was considered significant.
      RESULTS: Visibility with the digital images was statistically significantly
      higher for the carina, left lower lobe bronchus, bronchus intermedius, and
      vessels behind the heart and diaphragm. Subjective general quality impression of
      digital radiographs was also higher (P < 0.001). No significant visibility
      differences were found for pulmonary fissures or junctional lines. CONCLUSION:
      Subjective visibility of anatomic structures behind the heart and diaphragm and
      at the hilae is significantly improved with phosphor-based digital radiography
      compared with conventional screen-film radiography. This suggests that pathologic
      processes such as pulmonary nodules, masses or consolidations projected over
      those structures may be more easily and reliably depicted on digital than on
      conventional chest X-rays.

PMID- 16106774
TI  - Fatal traumatic heart wounds: review of 160 autopsy cases.
AB  - BACKGROUND: Despite many published retrospective analyses on cardiac injuries in
      treated patients, there is a striking scarcity of population-based studies that
      include autopsies. OBJECTIVES: To provide data on fatal traumatic heart wounds in
      autopsied cases. METHODS: We reviewed 2,487 medico-legal autopsy records from the
      morgue of the Bursa branch of the Turkish Council of Forensic Medicine for the
      period 1997-2001. RESULTS: Of these cases, 160 (6.4%) had cardiac injury; 13.8%
      were females and 86.2% males, and the mean age was 35.9 years (range 4-65). The
      most common cause of heart wounds was penetrating trauma (87.5%), namely sharp
      injuries (48.1%) and firearm injuries (39.4%). The two most common causes of
      blunt heart wounds were traffic accidents (5.6%) and falls from a height (5%).
      Rupture was present in 96.9% of the cases, and isolated left ventricle and
      isolated right ventricle were ruptured in 31.3% and 23.8%, respectively. In
      penetrating injury the risk of ventricle rupture was higher than of atrium
      rupture. Alcohol was detected in 16.3% of cases. Only 3.5% of the penetrating
      cardiac injury cases and 5% of the blunt cardiac injury cases were admitted to
      hospital. CONCLUSIONS: Given that only a very low percentage of the patients who
      sustain cardiac injury reach hospital alive, population-based studies, especially
      autopsy results, should be conducted to define the characteristics of cardiac
      injuries.

PMID- 16106775
TI  - Utility of routine coagulation studies in emergency department patients with
      suspected acute coronary syndromes.
AB  - BACKGROUND: Many emergency departments use coagulation studies in the evaluation
      of patients with suspected acute coronary syndromes. OBJECTIVES: To determine the
      prevalence of abnormal coagulation studies in ED patients evaluated for suspected
      ACS, and to investigate whether abnormal international normalized ratio/partial
      thromboplastin time testing resulted in changes in patient management and whether
      abnormal results could be predicted by history and physical examination. METHODS:
      In this retrospective observational study, hospital and ED records were obtained
      for all patients with a diagnosis of ACS seen in the ED during a 3 month period.
      ED records were reviewed to identify patients in whom the cardiac laboratory
      panel was performed. Other data included demographics, diagnosis and disposition,
      historical risk factors for abnormalities of coagulation, ED and inpatient
      management, INR/PTT, platelet count and cardiac enzymes. Descriptive statistical
      analyses were performed. RESULTS: Complete data were available for 223 of the 227
      patients (98.7%). Of these, 175 (78.5%) were admitted. The mean age was 64.2
      years. Thirteen patients (5.8%) were diagnosed with acute myocardial infarction.
      Of the 223 patients, 29 (13%) and 23 (10%) had INR and PTT results respectively
      beyond the reference range. Seventy percent of patients with abnormal coagulation
      test results had risk factors for coagulation disorders. The abnormal results of
      the remaining patients included only a mild elevation and therefore no change in
      management was initiated. CONCLUSIONS: Abnormal coagulation test results in
      patients presenting with suspected ACS are rare, they can usually be predicted by
      history, and they rarely affect management. Routine coagulation studies are not
      indicated in these patients.

PMID- 16106776
TI  - Removable fiberglass de-loading cast for the management of neuropathic plantar
      ulceration of the foot.
AB  - BACKGROUND: Neuropathic plantar ulceration of the foot is treated by de-loading
      the ulcer. The total contact cast is considered to be the gold standard, but it
      is a labor-intensive procedure and frequent cast changes are needed. OBJECTIVES:
      To describe an alternative de-loading method using a fiberglass removable walking
      cast. METHODS: This prospective uncontrolled study comprised 24 diabetic and non
      diabetic patients with a single planter neuropathic ulcer. Exclusion criteria
      included the presence of osteomyelitis or cellulites, peripheral vascular
      disease, severe foot or leg edema, more than one ulcer on the treated foot,
      ulcers on the other foot, visual problems, gait instability, and personality or
      psychiatric problems. All patients were treated with the removable fiberglass de
      loading cast. At each weekly follow-up visit the cast was removed. Data were
      collected using a clinical report form. RESULTS: The ulcer healed completely in
      21 of the 24 patients treated (87.5%). The mean time for healing was 6.8 weeks
      (range 3-20 weeks, SD = 4.2). New ulcers developed in six patients (25% of the
      group). CONCLUSIONS: The effectiveness and safety of the method is comparable to
      that of the total contact cast, but is less labor intensive because the cast is
      manufactured only once and serves for the whole length of treatment. Improving
      the technique is expected to lower the complication rate.

PMID- 16106777
TI  - Risk for motorcyclists in a busy metropolitan city: the example of Tel Aviv.
AB  - BACKGROUND: The proportion of motorcyclists injured in road accidents in Israel
      is larger than their proportion among road users. OBJECTIVES: To identify factors
      contributing to the risk of injury motorcyclists as compared to drivers of other
      motor vehicles. METHODS: We retrieved and analyzed National Trauma Registry data
      on drivers, aged 16 and above, who were involved in traffic accidents and
      hospitalized between 1 January 1997 and 30 June 2003. RESULTS: The study group
      comprised 10,967 patients: 3,055 (28%) were motorcyclists and 7,912 (72%) were
      drivers of other motor vehicles. A multiple logistic regression revealed that Tel
      Aviv, the busiest metropolitan city in Israel, is a risk for motorcycle injury as
      compared to other regions; males have an increased risk compared to females; and
      age is a protecting factor since the risk of injury as a motorcyclist decreases
      as age increases. Nevertheless, the population of injured motorcyclists in Tel
      Aviv was significantly older (mean age 32.5 years vs. 28.6 elsewhere; t-test P <
      0.0001). Twenty percent (n = 156) of the injured motorcyclists in Tel Aviv were
      injured while working, compared to 9.5% (n = 217) in other regions (chi-square P
      < 0.0001). Motorcycle injuries in Tel Aviv were of lower severity (7.7% vs. 16.4%
      according to the Injury Severity Scale 16+, chi2 P < 0.0001), and had lower
      inpatient death rates (1.2% vs. 2.5%, chi2 P = 0.001). CONCLUSIONS: Tel Aviv is a
      risk for motorcycle injury compared to other regions, males have an increased
      risk compared to females, and age is a protecting factor. The proportion of
      motorcyclists in Tel Aviv injured while working is double that in other regions.

PMID- 16106778
TI  - Breast-feeding patterns in Central Israel.
AB  - BACKGROUND: The rate of breast-feeding in Israel has increased over the last two
      decades but is still lower than rates in other developed countries that have
      taken an active role in promoting breast-feeding. OBJECTIVE: To determine breast
      feeding patterns and the association between sociodemographic characteristics and
      breast-feeding in the Tel Aviv district. METHODS: The mothers of infants aged 2,
      4, 6 and 12 months, attending 59 well-baby clinics in the Tel Aviv district, were
      interviewed by telephone. Singleton infants who weighed less than 2,000 g and
      multiple-gestation infants were excluded from the study. The questions covered
      background data, sociodemographic characteristics of the family, and breast
      feeding practices. Stepwise logistic regression was used to analyze the
      association between breast-feeding and various sociodemographic characteristics.
      RESULTS: Altogether, 78.5% of the mothers (1,307/1,665) initiated breast-feeding.
      The rate of breast-feeding at 2, 4, 6 and 12 months was 55.8, 36.8, 29.9 and
      11.8%, respectively. Only 35.8% of the infants at 2 months and 11.2% at 6 months
      were exclusively breast-fed. The mean duration of breast-feeding was 5.2 +/- 0.2
      months. Grand multiparas (> or = 5 children) had a significantly higher rate of
      breast-feeding than women with one to four children (P < 0.001). More likely to
      breast-feed for 2 weeks or longer were women married to Yeshiva students (odds
      ratio = 5.3), women with > or = 13 years education (OR = 2.1), and women on
      maternity leave (OR = 1.6). The predictors for breast-feeding for 6 months or
      longer were similar. CONCLUSIONS: Although the rate of breast-feeding initiation
      in central Israel was 78.5%, only 29.9% of the mothers continue to breast-feed
      for 6 months. Already at a young age, an appreciable number of breast-fed infants
      receive infant formula. Breast-feeding promotion should focus on less educated
      women, homemakers, and families with one to four children.

PMID- 16106779
TI  - Biologic behavior of microsatellite-unstable colorectal cancer and treatment with
      5-fluorouracil.
AB  - Colorectal cancers develop as a consequence of genomic instability.
      Microsatellite instability is involved in the genesis of about 15% of sporadic
      colorectal cancers and in most hereditary non-polyposis cancers. High frequency
      MSI has been associated with a favorable prognosis, however it is not clear
      whether this is because MSI-H tumors are inherently less aggressive or because
      they are more sensitive to chemotherapy. Chemotherapy with a combination of 5
      fluorouracil and leukovorin or levamizole has been the standard of care for high
      risk stage II and stage III CRC; it is also used in stage IV CRC. Several in
      vitro studies have shown that colon cancer cell lines displaying MSI-H are less
      responsive to fluorouracil than microsatellite-stable cell lines. Human studies,
      all of them retrospective, yielded conflicting results. The selection of patients
      with CRC for 5-FU treatment has been based so far on the stage of the tumor
      rather than the biology of the tumor. Although surgical staging is highly
      predictive of survival, there are indications that the form of genomic
      instability within a patient's colorectal tumor has clinical implications, with
      and without 5-FU treatment. This review suggests that patients with MSI-H
      colorectal tumors may not benefit from 5-FU-based chemotherapy and can avoid its
      potential side effects (nausea, diarrhea, stomatitis, dermatitis, alopecia, and
      neurologic symptoms) that occur in half the treated patients. If confirmed by
      future prospective randomized controlled studies, these findings would indicate
      that microsatellite-instability testing should be conducted routinely and the
      results used to direct rational adjuvant chemotherapy in colon cancer.

PMID- 16106780
TI  - Telemedicine: why the delay?

PMID- 16106781
TI  - More Q's than A's in chronic Q fever hepatitis.

PMID- 16106782
TI  - Chronic Q fever hepatitis.

PMID- 16106783
TI  - Ischemic finger ulcer as a presenting symptom of systemic sclerosis.

PMID- 16106784
TI  - Schistosomiasis and acute appendicitis.

PMID- 16106785
TI  - Phencyclidine-induced multi-organ failure.

PMID- 16106786
TI  - Birth weight and gestational age.

PMID- 16106787
TI  - Inflammatory abdominal aortic aneurysm.

PMID- 16106788
TI  - [The new Asklepios Glykon].
AB  - In the Roman Empire a close relationship between religion and medicine existed
      within everyday medical cultures. This can be particularly demonstrated for the
      Asklepios medicine of the Imperial age: religion and medicine were equal and
      interwoven components which characterized this independent form of medical
      practice. Lucian of Samosata reported on the Asklepios of Abonuteichos in his
      "Alexandros or the False Prophet". Contrary to most interpretations, in this
      study Lucian's text is evaluated and used as a historical source, and the
      following points are made: the "Alexandros" is fruitful for understanding
      Imperial religious history; and for the cult of Asklepios in Abonuteichos it is a
      key source. However, in contrast to earlier research on this topic, it is shown
      that only a few rudimentary statements concerning the medical practice of
      Asklepios in Abonuteichos can be gained from this source. While a historical
      analysis of the "Alexandros" leads to a better understanding of the healing cult
      aspects of the worship of Asklepios, the precise relationship between religion
      and medicine in Abonuteichos, and thus the actual character of Asklepios
      medicine, remains unclear.

PMID- 16106789
TI  - [The health policy of the "Council of the People's Representatives": the German
      revolution 1918/1919 in medical historical perspective II: health policy as a
      factor of continuity and stability].
AB  - Most important for the events at the turn of 1918/19 was the coincidence of the
      revolution and the end of the war. This meant that in a very short time the
      troops had to be withdrawn from the front, the size of the army had to be
      reduced, and the wartime economy had to be transformed into a peace economy.
      Apart from the resulting economical and social problems, military demobilisation
      was closely linked with medical and health political difficulties. The
      revolutionary government saw itself as a provisional arrangement to ensure the
      unity of the state and the functioning of the German Reich. The maintenance of
      medical care and provision of a minimum of foodstuffs made health policy
      important during the months of revolution. Despite a positive balance of payments
      and a "health policy of continuity", the revolutionary government was unable to
      win the medical profession for its aims, because it failed to dispel suspicions
      that the medical profession was going to be socialised.

PMID- 16106790
TI  - [Risking more freedom? Cyproterone acetate, sexual offenders and the German "Law
      on voluntary castration and other methods of treatment", 1960-1975].
AB  - Shortly after the fall of the National Socialist regime efforts were made in the
      Federal Republic of Germany to legislate anew on sterilisation and castration.
      For some experts, in particular sexologists and forensic psychiatrists in
      Hamburg, the question of the "treatment" of sexual offenders soon played a major
      role. In another research context an endocrinological substance showing anti
      androgenic effects was synthesised in 1961 at the Schering AG in Berlin. In 1966
      this substance, cyproterone acetate, was used for the first time to subdue the
      sexual drive. During parliamentary debates on a reintroduction of castration as a
      method of treatment for sexual deviations the advocates of cyproterone acetate
      succeeded in "inserting" their expertise into the "law on voluntary castration
      and other methods of treatment", which was adopted by the German Bundestag in
      January 1969. This paper discusses the interface between applied pharmacology,
      forensic psychiatry and sexology, and the politics leading to this law.

PMID- 16106791
TI  - Cholera, 2004.

PMID- 16106792
TI  - [Imaging of iatrogenic diseases].

PMID- 16106793
TI  - [Imaging features of drug-induced lung diseases].
AB  - Drug-induced lung diseases are an increasingly frequent cause of morbidity. Over
      350 drugs are now recognized as being implicated in drug-induced lung diseases.
      Early diagnosis is critical. Discontinuing the drug may result in regression of
      the adverse effect. Diagnosis is based on a history of drug exposure with a
      temporal relationship between the introduction of the drug and the onset of
      symptoms, histologic evidence of lung damage and exclusion of other causes of
      lung injury. Unfortunately there is no specific test available. Histologic and
      radiologic findings are often non specific and diagnosis can be difficult. Drugs
      can cause a constellation of distinct patterns of respiratory involvement and all
      anatomic compartments of the lungs may be involved. The most common patterns are:
      non specific interstitial pneumonia and fibrosis, pulmonary eosinophilia,
      hypersensitivity pneumonitis, pulmonary edema with or without diffuse alveolar
      damage, bronchiolitis obliterans organizing pneumonia, pulmonary hemorrhage and
      vasculitis. It is important to be familiar with their common radiologic
      appearances.

PMID- 16106794
TI  - [Imaging features of iatrogenic drug disorders].
AB  - Iatrogenic drug disorders should be considered when presented with a number of
      imaging findings mainly involving the nervous, musculoskeletal, gastrointestinal
      or genitourinary system. Care should be used when differentiating between imaging
      findings related to the underlying pathology and imaging findings related to drug
      related complications: examples include the impact of steroid therapy on bones
      and the impact of triple-drug anti-HIV therapy and its impact of fatty tissue.
      Knowledge of the necessary imaging surveillance protocol is implied.

PMID- 16106795
TI  - [Iatrogenic complications from contrast materials].
AB  - Iodinated or gadolinium-based contrast agents are usually well tolerated, but
      some adverse events can happen due to a direct toxicity of the injected molecule
      (contrast-induced nephropathy, abnormal thyroid function), or to an indirect
      effect like in true allergic reactions. Radiologists must be familiar with the
      possibility of adverse events from contrast agents or injection procedures, and
      should be able to treat the patient. Also, they should take all necessary actions
      to minimize the occurrence of possible reactions in the presence of risk factors.

PMID- 16106796
TI  - [Risks associated with MRI: safety rules, incidents, and accidents].
AB  - It is now accepted that MR imaging does not present any biological risk for
      humans, even in cases of repeated exposure. However, several of the MR components
      (magnetic field, gradients, RF pulses, electrodes...) may cause some
      inconveniences to patients, most of them being reversible. However, severe
      accidents have been reported. Even though screening of patients for MR imaging
      eligibility is performed to identify patients with contra-indications to MRI, the
      lack of vigilance or the ignorance of certain basic safety requirements could
      lead to serious adverse effects, including death. The goal of this article is to
      review the various accidents reported with MRI, to explain their mechanism, and
      to describe means of prevention.

PMID- 16106797
TI  - [Risks and responsibilities in diagnostic and interventional radiology. Ethical
      and medicolegal considerations].
AB  - Medical risk management has one main purpose: to ensure the safety of care. The
      law of March 2002 has generated a true cultural revolution. The radiologist is
      involved with new and difficult areas of medical liability due to technical
      advances, the increasing number of imaging techniques, the increasing complexity
      of imaging techniques, their efficiency and the need for multidisciplinary
      approach. Imaging recommendations requiring increasing levels of technical and
      clinical skills. The radiologist is liable with regards to the indications of
      imaging studies, and also with regards to informed consent. The prevention of
      medicolegal problems is achieved by competency, which must be combined to good
      liability insurance and ongoing vigilance supported by appropriate continuous
      medical education.

PMID- 16106798
TI  - [Complications of fluoroscopy-, ultrasound-, and CT-guided percutaneous
      interventional procedures].
AB  - The purpose of this article is to describe potential complications following the
      most common image-guided (fluoroscopy, ultrasound or CT) percutaneous
      interventional procedures, both diagnostic and therapeutic, thoraco-abdominal and
      musculoskeletal, as well as to review risk factors and the best practice
      recommendations. Prior to any interventional procedure, it is necessary to
      ascertain the absence of any abnormality in coagulation, to secure enough time to
      explain the procedure to the patient, and to adhere to strict sterile technique.
      Indeed, infections and hemorrhagic complications are the principal causes of
      mortality and morbidity for all procedures. Following lung biopsy, CT scan
      detects an immediate pneumothorax in 30% of patients. Major complications
      following percutaneous liver biopsy occur within 3 to 6 hours. Following a
      percutaneous drainage, complications occur in less than 10% of cases. Following a
      radiofrequency thermal ablation of malignant tumors, the mortality rate is low
      (0,5 to 1,4%), infection and hemorrhage are the most frequent complications.
      While rare, septic arthritis is the main complication that can follow
      musculoskeletal procedures and is a cause of medical malpractice lawsuits brought
      by patients.

PMID- 16106799
TI  - [Complications of fluoroscopy-, ultrasound-, and CT-guided percutaneous
      interventional procedures].

PMID- 16106800
TI  - [Risk from prenatal exposure to ionizing radiation].
AB  - Exposure to ionizing radiation during pregnancy always is a worrisome event.
      Knowledge of teratogenic and carcinogenic mechanisms based on reliable scientific
      data (ICRP 84) allows appropriate management of patients following exposure to
      ionizing radiation. Radiation exposure in the setting of diagnostic imaging
      studies is not associated with an increased risk of fetal malformation; however,
      the risk of childhood malignancy is minimally increased. This information must be
      provided to parents so they may reach an informed decision with regards to the
      outcome of the pregnancy. The analysis of the quality and quantity of exposure
      should be limited to imaging examinations where the abdomen was exposed.
      Management will be based on the type of exposure. Guidelines are provided for
      various exposure situations and all radiologists must be able to manage such
      situations.

PMID- 16106801
TI  - [Risk from prenatal exposure to ionizing radiation].

PMID- 16106802
TI  - [A new method of visual exploration analysis].
AB  - The term visual field corresponds to the angular field of view that is seen by
      the eyes when they are fixed on a point straight-ahead. In neurological patients-
      e.g. stroke, trauma, or tumour patients--visual field function can be restricted,
      depending on lesion site and size. In contrast, the term "functional visual
      field" describes the area of visual field responsiveness under more ordinary
      viewing conditions. The visual exploration, i.e. the capacity to explore and
      analyze our visual world, is dependent on the integrity of the visual system and
      the oculomotor system which has to move the fovea from one object of interest to
      the next. In this paper, we present a new method to assess the functional visual
      field, conceptualized as the area that a patient actively scans with eye
      movements to detect predefined targets placed on everyday scenes. This method
      allows us to compare three levels of visual field function: (a) the spatial
      distribution of successful search (hits, i.e. which targets did the patient
      find?), (b) the spatial distribution of fixations (i.e. where did the patient
      preferentially search for targets?), and (c) the retinotopic level (i.e. the
      visual field assessed by perimetry). By integrating these three levels, one can
      evaluate functional outcomes of visual field disorders. Of particular importance
      is the question of how a patient compensates for a visual field loss with
      appropriate eye movements. A further clinical application of this method is the
      comparison of pre- with post-treatment data. Patients with visual field disorders
      usually undergo specific exploration trainings, aimed at enhancing the number and
      amplitude of saccades towards the region of the visual field deficit. The first
      experiences and clinical application with this method are presented here.

PMID- 16106803
TI  - [The optic neuropathies].
AB  - Clinical diagnosis of optic neuropathies is based on the association of visual
      loss, altered color vision, relative afferent pupillary defect (if the optic
      neuropathy is unilateral), and changes in optic nerve appearance. Clinical
      characteristics often allow an etiologic diagnosis. This article emphasizes the
      two most common causes of optic neuropathies: inflammatory optic neuritis in
      younger people and anterior ischemic optic neuropathy in older people.

PMID- 16106804
TI  - [Painful oculomotor palsy: a diagnostic approach].
AB  - We review the question of diagnosis of painful and relatively isolated
      ophthalmoplegia due to diseases affecting the ocular motor nerves. For each
      clinical setting, we provide an overview of the main causes and a practical way
      to approach the diagnosis. As vascular malformations should always be kept in
      mind in patients with painful ophthalmoplegia, emergency neuroradiological
      investigations may be needed. However, the etiological scope is wide and the
      rationale for choosing the more appropriate examination and its optimal timing
      depends exclusively on the clinical evaluation. Despite advances in investigation
      techniques, diagnosis may remain difficult or even unresolved in a certain number
      of patients. We discuss successively paralysis of the third, sixth and fourth
      nerve, paralysis of several ocular motor nerves, recurrent ophthalmoplegia and
      ischaemic ocular motor palsies, which are the most frequent cause.

PMID- 16106805
TI  - [Atypical ocular myasthenia gravis].
AB  - The diagnosis of ocular myasthenia gravis is rarely in doubt in patients with a
      proper history and typical clinical findings. However, myasthenia gravis can
      mimick any pupil-sparing eye movement disorder and several diseases may
      masquerade myasthenia gravis. We review the atypical presentations and
      differential diagnoses in ocular myasthenia gravis, describing four patients with
      some of these conditions (4th nerve palsy, near spasm reflex, one-and-a-half
      syndrome, orbital meningioma). The correct interpretation of the clinical
      findings associated with appropriate neuro-imaging studies allowed the
      appropriate diagnosis in these cases.

PMID- 16106806
TI  - [From the abducens nucleus to spatial memory: an ocular motor journey].
AB  - Advances in our knowledge on eye movements over the last 25 years are reviewed,
      focusing on the author's experience. First, the advantages of binocular frontal
      vision, which is a common characteristic of all predator mammals, are compared to
      those of lateral vision, characterizing their preys. Binocular frontal vision
      implies a perfect parallelism of both eyes, which is ensured in the pons by means
      of the abducens nucleus, controlling abduction as well as adduction. The
      pathological example of the "one-and-a-half" syndrome, in which the abducens
      nucleus and the adjacent medial longitudinal fasciculus are simultaneously
      impaired, is described. The main brainstem syndromes involving vertical eye
      movements are also reviewed: in particular, the third nerve nucleus syndrome, in
      which both ipsilateral third nerve paralysis and contralateral superior rectus
      paralysis (with hypotropia) result from a unilateral third nerve nucleus lesion.
      A case of upbeat nystagmus (in the primary position of gaze) due to a small upper
      pontine lesion, probably affecting the ventral tegmental tract (VTT) is also
      reported. This is an opportunity to emphasize that, although a number of cases of
      upbeat nystagmus due to focal brainstem lesions affecting the upward vestibular
      pathway (UVP)--either at the upper pontine (VTT) or caudal medullary level--exist
      in the literature, no convincing cases with downbeat nystagmus (in the primary
      position of gaze) due to a focal brainstem lesion have been reported. Downbeat
      nystagmus could result from a UVP hyperactivity (secondary to a floccular lesion)
      and the notion that this pathway is physiologically predominant compared to the
      downward pathway, maybe due to gravity, is developed. A new hypothesis about the
      role of the caudal medulla in UVP is also proposed. Next, the cortical control of
      saccadic eye movements is reviewed, with a reminder that reflexive saccades are
      mainly triggered by the parietal eye field whereas intentional saccades depend
      upon the frontal eye field. The inhibition of reflexive saccades is mainly
      controlled by the dorsolateral frontal cortex (DLPFC), i.e. area 46 of Brodmann.
      A few examples of the use of saccades as a research tool and model in cognitive
      neurosciences are given. The use of memory-guided saccades allowed us to study
      spatial memory and led us to propose a relatively original conception of the
      cortical control of spatial memory in which the DLPFC, the parahippocampal cortex
      and the hippocampal formation could be involved successively according to
      specific periods of time. An experiment using functional magnetic resonance
      imaging in a paradigm studying decision is described, again with the involvement
      of the DLPFC in the decisional process. Lastly, the usefulness of eye movements
      in clinical neuro-ophthalmology at the bedside as well as in neurophysiological
      or even neuropsychological research in the laboratory is emphasized.

PMID- 16106807
TI  - [Transient trochlear nerve palsy as the presenting neurological sign of
      panarteritis nodosa].
AB  - INTRODUCTION: Panarteritis nodosa (PAN) is a systemic vasculitis affecting small
      and medium-sized arteries. Neuro-ophthalmological complications of PAN are rare
      but numerous, and may affect the eye, the visual and the oculomotor pathways.
      Such complications occur mainly in patients previously diagnosed with PAN.
      OBSERVATION: A 51-year-old woman presented with an isolated right trochlear (IV)
      palsy, in the setting of headaches and fluctuating fever of unknown etiology.
      Erythrocyte sedimentation rate was 13 mm and full blood cell count was normal.
      Previous chest X-ray and blood studies were negative for an infection or
      inflammation. Orbital and cerebral CT scan was normal. Spontaneous recovery of
      diplopia ensued over four days. Two days later, paresthesia and sensory paresis
      of the dorsal portion of the left foot were present. Lumbar puncture revealed 14
      leucocytes (76 percent lymphocytes) with elevated proteins, but blood studies and
      serologies were negative. A diagnosis of undetermined meningo-myelo
      radiculoneuritis was made. Because of a possible tick bite six weeks previously
      the patient was empirically treated with 2 g intravenous ceftriaxone for 3 weeks.
      Fever rapidly dropped. Six weeks after the onset of diplopia, acute onset of
      blindness in her right eye, diffuse arthralgias and fever motivated a new
      hospitalization. There was a central retinal artery occlusion of the right eye.
      Blood studies now revealed signs of systemic inflammation (ESR 30 mm, CRP 12
      mg/L, ANA 1/80, pANCA 1/40, leucocytosis 12.4 G/L, Hb 111 g/L, Ht 33 percent).
      Biopsy of the left sural nerve revealed arterial fibrinoid necrosis. A diagnosis
      of PAN was made. CONCLUSIONS: Transient diplopia can be the heralding symptom of
      a systemic vasculitis such as PAN, giant cell arteritis and Wegener
      granulomatosis. In this patient the presence of accompanying systemic symptoms
      raised a suspicion of systemic inflammation, but the absence of serologic and
      imaging abnormalities precluded a specific diagnosis initially. A few weeks
      later, the presence of a second ischemic event (retinal) and positive blood
      studies led to a further diagnostic procedure. Oculomotor and abducens palsies
      have rarely been reported in association with PAN. We report the first case of
      trochlear nerve paresis as the inaugural neurological sign of PAN. This case
      highlights the importance of considering inflammatory systemic disorders in
      patients with acute diplopia particularly when they are young, lack vascular risk
      factors or cause, and complain of associated systemic symptoms.

PMID- 16106808
TI  - [Optic neuritis in cat scratch disease].
AB  - Ocular and neuro-ophthalmic manifestations of cat scratch disease are not
      uncommon. The association of anterior optic neuritis with retinal lesions
      suggests neuroretinitis, which is highly suggestive of cat scratch disease. A new
      case is described.

PMID- 16106809
TI  - [Intermittent diplopia after prolonged downward gaze to the right: what is the
      differential diagnosis?].
AB  - In general, intermittent diplopia evokes suspicion of ocular myasthenia gravis.
      However, other etiologies such as Brown syndrome or myokymia of the superior
      oblique may provoke intermittent diplopia. We present a case of intermittent
      diplopia due to a tumor in the cavernous sinus. A 59-year-old patient reported
      intermittent diplopia after prolonged downward gaze to the right. All other gaze
      directions failed to provoke symptoms. In 1992, the diagnosis of inactive
      macroadenoma of the pituitary gland was established and the patient underwent
      surgery and radiation therapy. At physical examination, prolonged downward gaze
      to the right of about 2 minutes provoked paresis of abduction, slight ptosis, and
      restriction of elevation on the left side, corresponding to sixth nerve palsy and
      palsy of the superior branch of the third nerve on the left side. MRI showed a
      relapse of the macroadenoma with infiltration of the cavernous sinus on the left
      side. The patient underwent surgery then focal radiation (gamma-knife). The
      clinical course was favourable and at the follow-up examination six months later,
      no diplopia was reported.

PMID- 16106810
TI  - [Heidenhain's variant of Creutzfeldt-Jakob's disease].
AB  - INTRODUCTION: Creutzfeldt-Jakob's disease has various anatomoclinical
      presentations including a rare form with preponderant visual signs described by
      Heidenhain. In this form, the visual symptoms may be isolated for a few weeks,
      leading to multiple ophthalmological examinations. OBSERVATION: We report the
      case of a 75-year-old woman who developed isolated visual disorders which rapidly
      increased over a period of two months. Addition of neurological symptoms,
      abnormalities of EEG and positivity of 14-3-3 protein led to the diagnosis of
      Creutzfeldt-Jakob's disease. The patient died 14 months after the first
      neuroophthalmologic signs. The diagnosis was established by post-mortem
      examination and immuno-electrophoretic demonstration of type 1 prion protein.
      CONCLUSION: Heidenhain's form of Creutzfeldt-Jakob's disease highlights the
      importance of general rules for prevention of iatrogenic hazard during
      ophthalmological examinations.

PMID- 16106811
TI  - [Bilateral third cranial nerve palsy triggered by an acute relapse of multiple
      sclerosis].
AB  - INTRODUCTION: We report a case of bilateral third cranial nerve palsy in a
      patient with a secondary progressive multiple sclerosis. OBSERVATION: MRI
      revealed a large hyperintense lesion in T2-weighted images in the mesencephalic
      area. The clinical and radiological outcome was good after intravenous
      methylprednisolone. The oculomotor signs were probably caused by this
      mesencephalic lesion. CONCLUSION: This case of bilateral third cranial nerve
      palsy is, to our knowledge, the first one occurring in a patient with multiple
      sclerosis.

PMID- 16106812
TI  - [Pituitary apoplexy].
AB  - Pituitary apoplexy is a life threatening condition caused by sudden hemorrhage or
      infarction of the pituitary gland. Most patients present with headaches and neuro
      ophthalmologic symptoms and signs, often associated with altered mental status.

PMID- 16106813
TI  - [Complete ophthalmoplegia complicating ophthalmic herpes zoster].
AB  - We report a case of a 73-year-old patient with complete ophthalmoplegia following
      an episode of ophthalmic herpes zoster. MRI showed an associated ipsilateral
      temporal meningioma with cavernous sinus extension. We discuss the possible
      responsibility of these two conditions in the ocular motor signs.

PMID- 16106814
TI  - [Convergence nystagmus and vertical gaze palsy of vascular origin].
AB  - A case of convergence-retraction nystagmus with upward vertical gaze paralysis
      and skew deviation (right hypotropia), without any other neurological signs, is
      reported. The probably vascular lesion was located at the mesodiencephalic
      junction, lying between the right border of the posterior commissure, the right
      interstitial nucleus of Cajal and the periaqueductal grey matter, accounting for
      the three ocular motor signs. The particular interest of this case is due to the
      relative smallness of the lesion.

PMID- 16106815
TI  - [Isolated ptosis in a 58-year-old woman].
AB  - A 60-year-old woman who had experienced isolated ptosis for two years was seen
      when it had been fixed for one year. She had a personal and familial history of
      stromal corneal dystrophy. The diagnosis of mitochondrial cytopathy was made on
      the basis of clinical, electrophysiological, biological and histological
      findings. Surgical repair of the ptosis allowed visual recovery. The relationship
      between ptosis, corneal dystrophy and mitochondrial cytopathy is discussed.

PMID- 16106816
TI  - [Rapid onset of visual recovery following acute visual loss due to leber's
      hereditary optic neuropathy].
AB  - INTRODUCTION: Leber's hereditary optic neuropathy (LHON) is a maternally
      inherited disorder affecting the optic nerves in which the typical clinical
      presentation is subacute, painless, sequential visual loss in young adult males.
      Patients with LHON who have atypical clinical features may be initially
      misdiagnosed. OBSERVATION: An 8-year-old boy developed an acute severe bilateral
      optic neuropathy associated with pain and mild optic disc edema. Molecular
      genetic testing of his mitochondrial DNA revealed two point mutations, T14484C
      and G15257A. His vision began to improve within one month of onset of visual loss
      and eventually recovered to 20/15 in both eyes. Four years previously, his oldest
      sister had acutely lost vision in both eyes at age 12 years. Her young age,
      female gender, the bilateral visual loss associated with pain, optic disc edema,
      absent family history of visual loss and negative workup were felt to be most
      consistent with a clinical diagnosis of idiopathic optic neuritis of childhood.
      Her visual recovery which began within two months of visual loss further
      supported the diagnosis. She was retrospectively re-diagnosed with LHON after her
      younger brother was genetically confirmed. CONCLUSION: We describe two siblings
      with LHON whose time course from onset of visual loss to onset of visual recovery
      was unusually rapid. Because of other atypical features for LHON such as their
      young age at presentation, bilateral simultaneous visual loss and associated
      periorbital pain, their clinical profile appeared more typical of a demyelinating
      disease such as childhood optic neuritis. The first affected sibling (sister) was
      initially misdiagnosed. This report emphasizes that the clinical spectrum of LHON
      is variable and thus, LHON should be considered in any patient with an acute
      bilateral optic neuropathy, even in the absence of a positive family history.
      Correct diagnosis of this maternally inherited disorder is important for
      assessment of visual prognosis and appropriate genetic counseling.

PMID- 16106817
TI  - [Persistent visual problems thirty years after severe head trauma].
AB  - INTRODUCTION: Visual disturbances are common after severe head trauma. Some
      authors report 50 percent of these patients having damage to the visual system,
      ocular motor nerve palsies, or central eye movement disturbances. Visual
      disturbances influence prognosis and outcome of neurological rehabilitation, and,
      in most cases, diagnosis and treatment require interdisciplinary care. CASE
      REPORT: We report here a 50-year-old patient who suffered from severe head trauma
      at age 20. After coming out of a 4-week coma, he suffered visual disturbances
      such as blurred vision and diplopia. Visual acuity was 1.0 and the visual fields
      were intact. The symptoms remained unexplained for a long time. One year after
      the trauma, right trochlear palsy was diagnosed and surgical treatment was
      performed. However, the symptoms persisted, and one year later, a second
      operation was performed without changing the symptoms. During many years, prisms
      or refractive corrections were used to improve the visual disturbances, and
      finally, a psychiatric treatment was started. At age 40, the patient became
      presbyopic and his visual problems increased, especially for reading. When he was
      examined for the first time in our consultation, corrected visual acuity was 1.0
      with a small hyperphoria of the right eye. During careful examination of the eye
      downgaze, a conjugate pure torsional nystagmus was observed, which disappeared in
      primary gaze position. CONCLUSION: Pure torsional nystagmus is difficult to
      diagnose, especially when it is provoked only by one gaze direction such as in
      our patient. As a sequel of the severe head trauma with brainstem contusion, this
      type of nystagmus is a rare form of central vestibular nystagmus, and may by
      modified by head rotation or suppressed by convergence. The "treatment" of the
      patient's blurred vision when reading was easy by ordering goggles with a near
      part placed near the primary gaze position and a 6 base down prismatic
      correction. Reading was then possible without provoking torsional nystagmus.

PMID- 16106818
TI  - [Optochiasmal cavernoma: a rare cause of unilateral visual loss].
AB  - INTRODUCTION: Optic pathways cavernomas are rare vascular hamartomas that can
      present either with an acute chiasmal syndrome or slowly progressive visual loss.
      OBSERVATION: A 29-year-old patient presented with mild unilateral visual loss of
      rapid onset and monocular left temporal hemianopia. MRI disclosed a heterogenous
      enhancing optochiasmal lesion. Work-up found no evidence for an inflammatory,
      infectious or tumoral disease and therefore a neurosurgical approach of the
      lesion allowed diagnosis of cavernoma, confirmed by pathological examination.
      Successful resection resulted in partial recovery of the visual field.
      CONCLUSION: Optochiasmal cavernomas are rare, removal can improve visual outcome.

PMID- 16106819
TI  - [Report from the 57th Annual Meeting of the American Academy of Neurology].

PMID- 16106820
TI  - A hierarchical approach to coding chemical, biological and pharmaceutical
      substances.
AB  - This hierarchical coding system is designed to classify substances into
      successively subordinate categories on the basis of chemical, physical and
      biological properties. Although initially developed for occupational cancer
      epidemiological studies, it is general in nature and can be used for other
      purposes where a systematic approach is needed to catalogue or analyze large
      numbers of substances and/or physical properties. The coding system incorporates
      a multi level approach, where substances can be coded both on the basis of
      function and composition. On the first level, a three digit code is assigned to
      each substance to indicate its primary use in the occupational environment (e.g.
      pesticide, catalyst, adhesive). Substances can then be coded using a ten digit
      code to indicate structure and composition (e.g. organic molecule, biomolecule,
      pharmaceutical). Depending on the complexity required, analysis can incorporate
      the three digit code, ten digit code, or a combination of both. The approach to
      coding both chemical and biological agents is modeled in part after conventional
      approaches used by the International Union of Pure and Applied Chemists (IUPAC)
      and the International Union of Biochemists (IUB). Development of the coding
      system was initiated in the 1980's in response to a need for a system allowing
      analysis of individual agents as well classes or groups of substances. The
      project was undertaken as a collaborative venture between the BC Cancer Agency,
      Cancer Control Research program (then Division of Epidemiology) and the
      Department of Chemical and Biological Engineering at the University of British
      Columbia.

PMID- 16106821
TI  - [Not only one summer].

PMID- 16106822
TI  - [Finding the right approach].

PMID- 16106823
TI  - [A career in nursing has progressed].

PMID- 16106824
TI  - [Illness stories of women with cancer: life history and sick role are
      correllated].

PMID- 16106825
TI  - [Sex specific health care: are women ill in a different manner than men].

PMID- 16106826
TI  - [Nursing and physician communication exemplified by incontinence: sex plays a
      dual role].

PMID- 16106827
TI  - [Hormone replacement therapy in menopause: (not) a cure all medication].

PMID- 16106828
TI  - [Use of homeopathy in climacteric: it need not be only hormones].

PMID- 16106829
TI  - [Counseling and guidance exemplified by kinesthetic mobilization: knowledge
      fosters safety].

PMID- 16106830
TI  - [Hygiene in nursing-- 1: Hands can transmit invisible dangers] ].

PMID- 16106831
TI  - [Pain management in the elderly--3: complementary methods can improve pain
      control].

PMID- 16106832
TI  - [Hot summer in the nursing home: some do not like it hot].

PMID- 16106833
TI  - [From national prevention standard to internal "decubitus ulcer" guideline--2:
      Standardizing wounds and still treating them individually].

PMID- 16106834
TI  - [Discharge planning of patients with secondarily healing wounds].

PMID- 16106835
TI  - [Case management at the Burgau Therapy Center--2: Collaborative search for
      solutions and implementing plans].

PMID- 16106836
TI  - [Women in a nursing career: engaged--curious--competent].

PMID- 16106837
TI  - [From case to case: all beginnings are difficult].

PMID- 16106838
TI  - [Excursions to Scotland: where prevention is the program].

PMID- 16106839
TI  - [Position statement of the National Nursing Assessment Group of Germany:
      regarding the basic "nutrition and fluid requirements" policy of the elderly by
      the MDS (Medical Service of the Central Associations of the Health Insurance
      Companies), July 2003].
AB  - Assessing the nutritional state of old and dependent people demands a distinctive
      consideration of all aspects which might influence the individual's nutritional
      habits. An isolated consideration of the body mass index (BMI) does not serve the
      needs of elderly, because the BMI seems not to be a valid indicator for their
      nutrtional state. In order to prove the risk of malnutrition, also the individual
      life conditions as well as social, religious, cultural and economic circumstances
      besides the amount of energy and nu triments are to be taken into account.

PMID- 16106840
TI  - Local structures of ions at ion-exchange resin/solution interface.
AB  - The local structures of Cl- and Br- in anion-exchange resins have been studied by
      X-ray absorption fine structure (XAFS), and separation selectivity is discussed
      on the basis of results. When two different anion-exchange resins having
      trimethylammonium and dimethylammonium groups as anion-exchange groups are
      employed for ion-exchange experiments, slightly higher Br- selectivity has been
      obtained with the former. XAFS has indicated that the average hydration numbers
      for a given anion is not affected by the structure of the ion-exchange group, but
      that the extent of ion-association between the anion and the ion-exchange groups
      depends on the type of the ion-exchange group. Shorter interaction distance (and
      in turn stronger ion-association) has been confirmed for the dimethylammonium
      type resin, and is consistent with lower Br- selectivity of this resin.

PMID- 16106841
TI  - Factors affecting selectivity in ion chromatography.
AB  - Methods for separation of ions by ion-exchange, ion-pair, and zwitterion ion
      chromatography share at least one common thread--the induced formation of a
      cation-anion pair in the stationary phase. Selectivity can be defined as the
      relative ability of sample ions to form such a pair. Examples are given in anion
      exchange chromatography to show the effect of variations in the geometry,
      bulkiness and polarity of the resin cation on selectivity. The type of resin
      matrix, the hydrophobic nature of the resin surface and the degree of solvation
      also affect chromatographic behavior. The selectivity series observed in ion
      chromatography seems to be best explained by the interplay of two components:
      electrostatic attraction (ES) and the enforced-pairing (EP) that is brought about
      by hydrophobic attraction and by water-enforced ion pairing. Selectivity in ion
      pair chromatography (IPC) and in zwitterion ion chromatography (ZIC) is affected
      by both the mobile phase cation and anion. This leads to elution orders for
      anions that are different from conventional ion-exchange chromatography (IC) of
      anions where cations are excluded from the stationary phase and have little
      effect on a separation. The elution order of anions in ZIC is similar to that in
      IC except for small anions of 2-charge, which are retained more weakly in ZIC. A
      unique advantage of ZIC is that sample ions can be eluted as ion pairs with pure
      water as the eluent and a conductivity detector. The mechanism for separation of
      anions on a zwitterionic stationary phase has been a subject for considerable
      debate. The available facts point strongly to a partitioning mechanism or a mixed
      mechanism in which partitioning is dominant with a weaker ion-exchange component.

PMID- 16106842
TI  - Preparation and applications of weak acid cation exchanger based on monodisperse
      poly(ethylvinylbenzene-co-divinylbezene) beads.
AB  - New technology is reported here for the synthesis of an effective weak acid
      cation exchanger for ion chromatography. Monodisperse macroporous
      poly(ethylvinylbenzene-co-divinylbezene) (PEVB-DVB) beads of 5 microm diameter
      were prepared by a two-step swelling and polymerization method. Then carboxyl
      groups were introduced by polymerization of maleic anhydride with unreacted vinyl
      groups on the resin beads, followed by hydrolysis of the maleic anhydride groups.
      A column packed with the carboxylate beads was used to separate alkali and
      alkaline earth metal ions in a single isocratic run. Separations were found to be
      better than those with similar resin particles that are simply coated with maleic
      acid. The columns containing the new particles were 100% compatible with solvents
      commonly used for HPLC. Additionally, the prepared column was stable and could be
      used for a long time in a wide range of pH. The column gave good resolution, low
      detection limits and good repeatability for the separation of common cations.
      Satisfactory results were also obtained for separations of organic amines and of
      common cations in rainwater.

PMID- 16106843
TI  - Determination of trace concentrations of bromate in municipal and bottled
      drinking waters using a hydroxide-selective column with ion chromatography.
AB  - The International Agency for Research on Cancer determined that bromate is a
      potential human carcinogen, even at low micro/l levels in drinking water. Bromate
      is commonly produced from the ozonation of source water containing naturally
      occurring bromide. Traditionally, trace concentrations of bromate and other
      oxyhalides in environmental waters have been determined by anion exchange
      chromatography with an IonPac AS9-HC column using a carbonate eluent and
      suppressed conductivity detection, as described in EPA Method 300.1 B. However, a
      hydroxide eluent has lower suppressed background conductivity and lower noise
      compared to a carbonate eluent and this can reduce the detection limit and
      practical quantitation limit for bromate. In this paper, we examine the effect of
      using an electrolytically generated hydroxide eluent combined with a novel
      hydroxide-selective anion exchange column for the determination of disinfection
      byproduct anions and bromide in municipal and bottled drinking water samples. EPA
      Methods 300.1 B and 317.0 were used as test criteria to evaluate the new anion
      exchange column. The combination of a hydroxide eluent with a high capacity
      hydroxide-selective column allowed sub-microg/l detection limits for chlorite,
      bromate, chlorate, and bromide with a practical quantitation limit of 1 microg/l
      bromate using suppressed conductivity detection and 0.5 microg/l using postcolumn
      addition of o-dianisidine followed by visible detection. The linearity, method
      detection limits, robustness, and accuracy of the methods for spiked municipal
      and bottled water samples will be discussed.

PMID- 16106844
TI  - Comparison of two cryptand separator columns for the determination of trace
      chloride in semiconductor-grade nitric acid.
AB  - Improved ion-chromatographic approaches for measuring trace chloride in nitric
      acid are presented. Two columns, the IonPac Cryptand A1 and a higher-capacity
      Cryptand prototype, were tested and compared. Also, the use of a Continuously
      Regenerated Anion Trap Column (CR-ATC) was evaluated for its ability to purify
      electrolytically generated eluent. Nitric acid (70%) was used as the test matrix
      and chloride was used as the test analyte; prior to injection, the nitric acid
      was diluted to 0.7% for the A1 column and to 2.8% for the prototype column.
      Chloride could be quantified in only 20 min on either column; detection limits
      computed for 70% HNO3 (at 95% confidence, alpha = beta = 2.5%) were 1.8 and 1.5
      ppm for the A1 and prototype columns, respectively. Results also showed that the
      CR-ATC was necessary for obtaining acceptable acid blanks.

PMID- 16106845
TI  - Comparisons of disposable and conventional silver working electrode for the
      determination of iodide using high-performance anion-exchange chromatography with
      pulsed amperometric detection.
AB  - The paper compared the performance of two kinds of silver working electrode in
      electrochemical detector-the disposable and conventional electrode for the
      determination of iodide using high-performance anion-exchange chromatography
      (HPAEC) hyphenated with pulsed amperometric detection (PAD). The comparisons were
      carried out on the time of equilibration, long and short-term reproducibility,
      limits of detection and linearity of calibration. Results showed that disposable
      working electrode manifested equal or better results than conventional working
      electrode and could be used for iodide analysis. Besides, the disposable
      electrode could work for consecutive 2660 min (about 44 h, 10 min needed for each
      run) with no degradation. Due to its "disposable" property, disposable working
      electrode could be discarded if the detection sensitivity decreased to 80% so the
      time for polishing and reconditioning was spared and good reproducible results
      could be obtained. At last, the disposable electrode was applied for the
      determination of iodide in soil and sea water samples with the spiked recovery
      ranging from 96-104% and the detection limit of 0.5 microg/L (10 microL
      injection, three times of the baseline noise).

PMID- 16106846
TI  - Chloride interference in the determination of bromate in drinking water by
      reagent free ion chromatography with mass spectrometry detection.
AB  - Bromate, a well known by-product of the ozonation of drinking water, has been
      included among the substances which have to be monitored in the drinking water
      according to the last EC Directive 251/98 on potable water with a regulated limit
      of 10 microg l(-1). The need of performing routine analysis at this limit is a
      driving force for the developing of new simple and sensitive methods of
      detection, which should be also able to overcome the effect of matrix
      composition. This work explored the use of mass spectrometry detection with
      electrospray ionisation hyphenated to a reagent free ion chromatograph with
      hydroxide gradient elution for the determination of bromate in drinking water.
      The use of a high capacity hydroxide selective column operated in gradient mode
      allowed to avoid the interference by carbonate peak, which moved to longer
      retention times. The effect of increasing chloride concentrations from 0 to 250
      mg l(-1), which is the guideline limit for drinking water in Directive 251/98/EC,
      was to decrease absolute mass spectrometric response and chromatographic
      efficiency and, on the consequence, to increase the effective detection limits.
      The effect of the chloride concentration on the detection of bromate is
      discussed.

PMID- 16106847
TI  - Stabilization of sulfide and sulfite and ion-pair chromatography of mixtures of
      sulfide, sulfite, sulfate and thiosulfate.
AB  - Ion chromatography of sulfide, sulfite, sulfate and thiosulfate in a mixture is
      often difficult because of instability of sulfide and sulfite, poor separation of
      sulfide from common anions such as bromide or nitrate and similar elution-times
      for sulfite and sulfate. An ion-pair chromatographic method for the determination
      of these sulfur anions has been established by stoichiometric conversion of
      sulfide and sulfite into stable thiocyanate and sulfate, respectively, prior to
      the chromatographic run. Sulfate, thiosulfate and thiocyanate were resolved on an
      octadecylsilica column with an acetonitrile-water mobile phase containing
      tetrapropylammonium salt (TPA) as an ion-paring reagent, and thiosulfate and
      thiocyanate in the effluent could be measured with a photometric detector (220
      nm) and sulfate with a suppressed conductivity detector. When an acetonitrile
      water (6:94, v/v) mobile phase (pH 5.0) containing 15 mM TPA and small amounts of
      acetic acid was used at a flow-rate of 0.6 ml min(-1), the three anions could be
      eluted within 32 min. Calibration plots of peak height versus concentration for
      sulfide (detected as thiocyanate) and thiosulfate gave straight lines up to 35
      and 60 microM, respectively. The calibration plot for sulfide coincided with that
      obtained by using thiocyanate. A calibration plot for sulfite, measured as
      sulfate, was also linear up to 135 microM and was in accord with that of sulfate.
      Each calibration plot gave a correlation coefficient greater than 0.999. For six
      replicates obtained for a mixture of 30.0 microM sulfide, 50.0 microM sulfite,
      50.0 microM sulfate and 20.0 microM thiosulfate, the proposed method gave a mean
      value of 30.1 microM with a standard deviation (SD) of 0.77 microM and a relative
      standard deviation (RSD) of 2.6% for sulfide, 101 microM (SD = 3.5 microM, RSD =
      3.5%) for the total of sulfite and sulfate and 20.1 microM (SD = 0.44 microM, RSD
      = 2.2%) for thiosulfate. Recoveries for sulfide, sulfite plus sulfate, and
      thiosulfate in hot-spring water samples using the proposed method were found to
      be quantitative.

PMID- 16106848
TI  - Trace level perchlorate analysis by ion chromatography-mass spectrometry.
AB  - Perchlorate is commonly used as an oxidant in solid fuel propellant for rockets
      and missiles. Recently perchlorate contamination was found in many aquifers
      associated with Colorado River and other sites. Perchlorate was also found at
      elevated level in crops that use contaminated water for irrigation. Ion
      chromatography with conductivity detection could be used to measure perchlorate
      levels in drinking and wastewaters as per United States Environmental Protection
      Agency method 314, but at lower levels and with complexity of the matrix there
      could be false positive and/or false negative. This study was done to demonstrate
      the detection of perchlorate with lower detection limit with high ionic matrix by
      ion chromatography-mass spectrometry.

PMID- 16106849
TI  - Trace anion determination in concentrated hydrofluoric acid solutions by two
      dimensional ion chromatography I. Matrix elimination by ion-exclusion
      chromatography.
AB  - Since years, ion exclusion chromatography (ICE) has been the standard method to
      separate strong acid analyte anions from concentrated weak acid matrices such as
      hydrofluoric acid (HF). In this work, the commercially available IonPac ICE-AS 1
      column was used to separate trace levels of chloride, nitrate, sulfate and
      phosphate from HF solutions at 20% (w/w). The efficiency of the separation was
      studied in more detail using techniques such as ion chromatography (IC),
      inductively coupled plasma optical emission spectrometry (ICP-OES) and ICP-mass
      spectrometry (ICP-MS). For 20% (w/w) HF solutions and at a water carrier flow
      rate of 0.50 ml/min, the cut window was set from 8.5 to 14.5 min. Under these
      conditions, analyte recoveries of better than 90% were obtained for chloride,
      nitrate and sulfate, but only about 75% for phosphate. The HF rejection
      efficiency was better than 99.9%. It was found that the ICP techniques, measuring
      total element levels and not species, yielded significantly higher recoveries for
      phosphorus and sulfur compared to IC. Evidence will be given that part of the
      added phosphorus (approximately 15% for an addition of 10 mg PO4/kg) is present
      as mono-fluorophosphoric acid (H2FPO3). In the case of sulfate, the difference
      between IC and ICP-MS could be attributed to an important matrix effect from the
      residual HF concentration.

PMID- 16106850
TI  - Trace anion determination in concentrated hydrofluoric acid solutions by two
      dimensional ion chromatography II. Method performance study with a hydroxide
      eluent and a low noise suppressor.
AB  - The two-dimensional ion exclusion chromatography/ion chromatography (ICE-IC)
      approach is considered to be the method of choice for the determination of trace
      anions in concentrated hydrofluoric acid (48-50%, w/w). In order to achieve lower
      detection limits, this method was for the first time used with electrolytically
      generated and purified hydroxide eluents in combination with a low noise
      electrochemical suppressor. Compared to carbonate based eluents, the achieved
      gain in peak height sensitivity for chloride, sulfate, nitrate and phosphate is a
      factor of 6, 7, 16 and 13, respectively. The instrumental detection limits, based
      on the background noise, are 2, 0.2, 0.4 and 1.4 microg/kg HF 50% (w/w) for the
      same anions. Their method detection limits, calculated according to SEMI, are all
      within the 6-10microg/kg HF 50% (w/w) range and thus at least 10 times lower than
      the current Tier C grade requirements. The chromatographic run time could be
      shortened with some 10 min by the use of a relatively fast high-capacity
      hydroxide selective anion exchange column.

PMID- 16106851
TI  - Development of an inorganic cations retention model in ion chromatography by
      means of artificial neural networks with different two-phase training algorithms.
AB  - This paper describes development of artificial neural network (ANN) retention
      model, which can be used for method development in variety of ion chromatographic
      applications. By using developed retention model it is possible both to improve
      performance characteristic of developed method and to speed up new method
      development by reducing unnecessary experimentation. Multilayered feed forward
      neural network has been used to model retention behaviour of void peak, lithium,
      sodium, ammonium, potassium, magnesium, calcium, strontium and barium in relation
      with the eluent flow rate and concentration of methasulphonic acid (MSA) in
      eluent. The probability of finding the global minimum and fast convergence at the
      same time were enhanced by applying a two-phase training procedure. The developed
      two-phase training procedure consists of both first and second order training.
      Several training algorithms were applied and compared, namely: back propagation
      (BP), delta-bar-delta, quick propagation, conjugate gradient, quasi Newton and
      Levenberg-Marquardt. It is shown that the optimized two-phase training procedure
      enables fast convergence and avoids problems arisen from the fact that every new
      weight initialization can be regarded as a new starting position and yield
      irreproducible neural network if only second order training is applied.
      Activation function, number of hidden layer neurons and number of experimental
      data points used for training set were optimized in order to insure good
      predictive ability with respect to speeding up retention modelling procedure by
      reducing unnecessary experimental work. The predictive ability of optimized
      neural networks retention model was tested by using several statistical tests.
      This study shows that developed artificial neural network are very accurate and
      fast retention modelling tool applied to model varied inherent non-linear
      relationship of retention behaviour with respect to mobile phase parameters.

PMID- 16106852
TI  - Aliphatic long chain quaternary ammonium compounds analysis by ion-pair
      chromatography coupled with suppressed conductivity and UV detection in lysing
      reagents for blood cell analysers.
AB  - A method has been developed which allows simultaneous determination of three
      linear alkyl trimethylammonium salts. Dodecyltrimethylammonium chloride,
      tetradecyltrimethylammonium bromide and hexadecyltrimethylammonium chloride are
      widely used as main active ingredients of lysing reagents for blood cell
      analyzers which perform white blood cells differential determination into two or
      more sub-populations by impedance analysis. The ion-pair on styrene-divinyl
      benzene chromatographic phase looks like a suitable, reliable and long term
      stable tool for separation of such quaternary compounds. The detection based on
      suppressed conductivity was chosen because of the lack of significance
      chromophores. A micromembrane suppressor device compatible with high solvent
      concentration (up to 80%) was used in order to minimize the conductivity
      background before the detection. In the present work we show how the chemical
      post column derivatization makes the alkyl chain detectable also by UV direct
      detection at 210 nm.

PMID- 16106853
TI  - Fluorometric determination of ammonium ion by ion chromatography using postcolumn
      derivatization with o-phthaldialdehyde.
AB  - A postcolumn fluorometric derivatization method for the determination of trace
      amounts of ammonium ion (microg/L level) under matrices with high concentrations
      of sodium and amino acids has been developed. In this method, ammonium ion was
      determined by ion chromatography combined with fluorometric detection (IC-FL) in
      less than 16 min. IC was performed in a high-capacity cation-exchange Dionex
      IonPac CS16 analytical column (250 mm x 5 mm) under isocratic conditions with 30
      mM methanesulfonic acid (MSA) as mobile phase at flow-rate 1.0 mL/min. To remove
      amino acid interference, the postcolumn derivatization based on the reaction of
      ammonia with o-phthaldialdehyde (OPA) and sulfite was applied. The excitation and
      emission wavelengths were 364 and 425 nm, respectively. The effects of pH,
      reaction temperature and time, OPA-reagent composition and concentration, and
      sample matrix were studied. The linear range and detection limit of this method
      were similar to the standard method. The IC-FL method with a postcolumn
      fluorometric derivatization allows the routine determination of ammonium ion in
      extreme matrices where the ratios of sodium and amino acids to ammonium are up to
      2,800,000:1 and 28,000:1, respectively.

PMID- 16106854
TI  - Determination of several sugars in serum by high-performance anion-exchange
      chromatography with pulsed amperometric detection.
AB  - In this paper, a sensitive, simple and direct method for simultaneous
      determination of glucose, ribose, isomaltose and maltose in serum sample by high
      performance anion-exchange chromatography coupled with integrated pulsed
      amperometric detection was developed. The four target analytes were easily and
      completely separated on an anion-exchange column at a flow-rate of 0.25 mL/min by
      binary step gradient elution in about 16 min and the two eluents were deionized
      water and 500 mM sodium hydroxide, respectively. The separated four analytes were
      detected directly by using a gold electrode and quadruple-potential waveform
      integrated pulsed amperometry without derivatization. Under the optimized
      conditions, when the injection volume was 25 microL, the detection limits (signal
      to-noise ratio equal to 3) for glucose, ribose, isomaltose and maltose were 0.92,
      7.50, 12.9 and 10.3 ng/mL, respectively. The calibration graphs of peak area for
      the four analytes were linear over two to three orders of magnitude with
      correlation coefficients greater than 0.998. R.S.D. of peak areas of the four
      analytes for five determinations were no more than 5.6%. The analytical method
      had been applied to the determination of glucose, ribose, isomaltose and maltose
      in real serum samples and good results with low relative standard deviation not
      more than 5.3% were obtained. The accuracy of the proposed method was tested by
      recovery measurements on spiked samples and good recovery results (98.1-107.9%)
      were obtained.

PMID- 16106855
TI  - Analysis of carbohydrates by anion exchange chromatography and mass spectrometry.
AB  - A versatile liquid chromatographic platform has been developed for analysing
      underivatized carbohydrates using high performance anion exchange chromatography
      (HPAEC) followed by an inert PEEK splitter that splits the effluent to the
      integrated pulsed amperometric detector (IPAD) and to an on-line single
      quadrupole mass spectrometer (MS). Common eluents for HPAEC such as sodium
      hydroxide and sodium acetate are beneficial for the amperometric detection but
      not compatible with electrospray ionisation (ESI). Therefore a membrane-desalting
      device was installed after the splitter and prior to the ESI interface converting
      sodium hydroxide into water and sodium acetate into acetic acid. To enhance the
      sensitivity for the MS detection, 0.5 mmol/l lithium chloride was added after the
      membrane desalter to form lithium adducts of the carbohydrates. To compare
      sensitivity of IPAD and MS detection glucose, fructose, and sucrose were used as
      analytes. A calibration with external standards from 2.5 to 1000 pmole was
      performed showing a linear range over three orders of magnitude. Minimum
      detection limits (MDL) with IPAD were determined at 5 pmole levels for glucose to
      be 0.12 pmole, fructose 0.22 pmole and sucrose 0.11 pmole. With MS detection in
      the selected ion mode (SIM) the lithium adducts of the carbohydrates were
      detected obtaining MDL's for glucose of 1.49 pmole, fructose 1.19 pmole, and
      sucrose 0.36 pmole showing that under these conditions IPAD is 3-10 times more
      sensitive for those carbohydrates. The applicability of the method was
      demonstrated analysing carbohydrates in real world samples such as chicory inulin
      where polyfructans up to a molecular mass of 7000 g/mol were detected as
      quadrupoly charged lithium adducts. Furthermore mono-, di-, tri-, and
      oligosaccharides were detected in chicory coffee, honey and beer samples.

PMID- 16106856
TI  - Simultaneous determination of creatinine, creatine, and UV-absorbing amino acids
      using dual-mode gradient low-capacity cation-exchange chromatography.
AB  - A simple and versatile cation-exchange chromatography technique for the
      simultaneous determination of urinary creatinine (Cre), creatine (Crn),
      methionine (Met), tyrosine (Tyr), phenylalanine (Phe), histidine (His), and
      tryptophan (Trp) was developed. A novel low-capacity cation-exchange column
      packed with a newly developed sulfoacylated hypercross-linked macroreticular
      polystyrene-divinylbenzene resin, referred to as TMR-A/75 (capacity: 75
      microequiv/column), was successfully used with a binary dual-mode gradient
      eluting system. Two solvents, (A) 25 mM phosphoric acid-methanol (30:70, v/v) and
      (B) 25 mM disodium hydrogenphosphate-methanol (30:70, v/v) were pumped through
      the column by programming solvent delivery ratios as 0 to 5 min: A-B (55:45, pH
      3.6); 5-21 min: A-B (49:51, pH 5.3); and 21-35 min: A-B (55:45, pH 3.6). The flow
      rate was simultaneously time-programmed to be 0.6 mL/min from 0 to 19 min and to
      be 1.0 mL/min from 19 to 35 min. This eluting system could permit the use of the
      UV detection at 210 nm. The analytes, Crn, Met, Tyr, His, Cre, Phe, and Trp, were
      well separated in this order in 27 min with minimum resolution of approximately
      2, and the cycle time was about 35 min. Retention time of each analyte was very
      reproducible with relative standard deviations (RSDs) between 0.05 and 0.38% (n =
      5). The peak area responses were also reproducible with RSDs between 0.74 and
      2.24% (n = 5). Calibration lines based on area data were linear from 1 to 1000
      microM with r2 values of 0.9998 (Crn), 0.9998 (Met), 0.9999 (Tyr), 0.9999 (His),
      1.0000 (Cre), 1.0000 (Phe), and 0.9999 (Trp). The method was applicable to the
      screening and/or chemical diagnosis of inherited metabolic disorders such as
      phenylketonuria (PKU), tyrosinemia, and Lowe syndrome. The creatinine ratios of
      diagnostic markers (microM/microM Cre) were easily determined. The Phe/Cre ratios
      for five urines from patients with PKU ranged from 0.162 to 0.521, and the
      Tyr/Cre ratio for tyrosinemia was 0.147. The ratios of Tyr/Cre, Phe/Cre, and
      Trp/Cre for Lowe syndrome were 0.497, 0.321, and 0.495, respectively. In
      contrast, the creatinine ratios for healthy newborns showed one digit lower than
      those for patients did. The developed method is very practical and can provide
      useful information and results for the clinical or biomedical researches with low
      analytical run costs.

PMID- 16106857
TI  - Analysis of iodinated X-ray contrast agents in water samples by ion
      chromatography and inductively-coupled plasma mass spectrometry.
AB  - In this paper, an analytical method for the determination of six iodinated X-ray
      contrast agents (amidotrizoic acid, iohexol, iomeprol, iopamidol, iopromide, and
      ioxitalamic acid), iodide, and iodate in water samples is presented. The method
      is based on a separation of the analytes by ion chromatography (IC) and a
      subsequent detection by inductively-coupled plasma mass spectrometry (ICP-MS).
      The method was optimised with respect to separation conditions (column type and
      eluent composition) and extensively validated. Without pre-concentration of the
      samples, limits of detection below 0.2 microg/l could be achieved whereby
      reproducibility was below 6% for all compounds under investigation.

PMID- 16106858
TI  - Comparative study on the analytical performance of three waveforms for the
      determination of several aminoglycoside antibiotics with high performance liquid
      chromatography using amperometric detection.
AB  - A preliminary comparative study was carried out on the analytical performances of
      a new six-potential waveform and other two detection waveforms, triple-potential
      waveform and quadruple-potential waveform. The analytical performances compared
      included signal response, background noise, signal/noise ratio and signal
      stability. Compared with triple-potential waveform and quadruple-potential
      waveform, the new six-potential waveform had higher signal response, signal/noise
      ratio, and sensitivity. As for determination reproducibility, the six-potential
      waveform also exhibited a slightly better performance than the other two
      waveforms. Under the selected experimental conditions based on the six-potential
      waveform, there is a linear correlation between peak area and concentration over
      two to three orders of magnitude for nine aminoglycoside antibiotics with a
      correlation coefficients better than 0.998 and the detection limits measured as
      three times the peak height signal-to-noise ratio for the nine aminoglycoside
      antibiotics were in the range of 0.0198-0.889 microg/mL. The proposed method had
      been used to analyze real gentamicin sulphate drug sample.

PMID- 16106859
TI  - Development of a comprehensive analytical method for phosphate metabolites in
      plants by ion chromatography coupled with tandem mass spectrometry.
AB  - This paper describes the development of a practical method for the analysis of
      phosphorus compounds with a focus on sugar phosphates from the model higher plant
      Arabidopsis thaliana by ion chromatography coupled to electrospray ionization
      tandem mass spectrometry (IC-ESI-MS-MS). After the analytical separation, the
      potassium hydroxide eluent was converted to water with an anion suppressor
      allowing the effluent from the IC to be connected to the mass spectrometer
      directly. In the optimized method, 17 phosphorous compounds (adenosine
      diphosphate (ADP), fructose 1,6-bisphosphate, fructose 2,6-bisphosphate, fructose
      6-phosphate, galactose 1-phosphate, glucose 1-phosphate, glucose 1,6
      bisphosphate, glucose 6-phosphate, mannose 6-phosphate, phosphoenol pyrvate, 3
      phosphoglyceric acid, ribulose 1,5-bisphosphate, ribulose 5-phosphate, ribose 5
      phosphate, sucrose 6-phosophate and uridine 5'-diphosphate-glucose (UDPG)) were
      determined. The linearity of response for these phosphorous compounds over the
      concentration range of 0 and 10 microM was better than 0.9993 in all cases. The
      minimum detection limit was between 0.01 and 2.50 microM for a 25 microL
      injection, and recovery rates for standard addition to the sample were within the
      range from 93% to 110%.

PMID- 16106860
TI  - Analysis of carbohydrates in plants by high-performance anion-exchange
      chromatography coupled with electrospray mass spectrometry.
AB  - A mass spectrometer was coupled to high-performance anion-exchange chromatography
      (HPAEC) with the help of electrochemical neutralization of the eluent and post
      column addition of lithium chloride for carbohydrate analysis. Parallel selective
      channels (single ion monitoring) were used to decrease the detection limits and
      separate unresolved peaks. The mass specific detection allowed the simultaneous
      analysis of a wide range of sugar alcohols, mono-, di- and oligosaccharides.
      Carbohydrates extracted from leaves of poplar submitted to drought stress were
      analyzed using pulsed amperometric detection (PAD), then mass spectrometry. It
      allowed the confirmation of peak attribution and the identification of salicin as
      a major compound in the extracts. Different responses to water deficit and re
      hydration were obtained for several carbohydrates, suggesting different roles in
      osmoprotection processes.

PMID- 16106861
TI  - Separation and simultaneous determination of four artificial sweeteners in food
      and beverages by ion chromatography.
AB  - In this paper, the separation and determination of four artificial sweeteners
      (aspartame, sodium cyclamate, acesulfame-K and sodium saccharin) by ion
      chromatography coupled with suppressed conductivity detector is reported. The
      four artificial sweeteners were separated using KOH eluent generator. Due to the
      use of eluent generator, very low conductance background conductivity can be
      obtained and sensitivity of sweeteners has been greatly improved. Under the
      experimental condition, several inorganic anions, such as F-, Cl-, NO3-, NO2-, Br
      , SO4(2)-, PO4(3)- and some organic acid such as formate, acetate, benzoate, and
      citrate did not interfere with the determination. With this method, good linear
      relationship, sensitivity and reproducibility were obtained. Detection limits of
      aspartame, sodium cyclamate, acesulfame-K, sodium saccharin were 0.87, 0.032,
      0.019, 0.045 mg/L, respectively. Rate of recovery were between 98.23 and 105.42%,
      99.48 and 103.57%, 97.96 and 103.23%, 98.46 and 102.40%, respectively. The method
      has successfully applied to the determination of the four sweeteners in drinks
      and preserved fruits.

PMID- 16106862
TI  - Ion-pair chromatography of bis (sodium-sulfopropyl) disulfide brightener in
      acidic copper plating baths.
AB  - Quantitative analysis of the brightener component bis (sodium-sulfopropyl)
      disulfide (SPS) in acidic copper plating baths poses a real challenge due to the
      complex chemical matrix containing large amounts of Cu(II) ion and sulfuric acid
      together with other organic additives and additive decomposition products. We
      developed a new ion-pair chromatography method to analyze micro-molar amounts of
      SPS directly in plating bath samples without the need for sample pre-treatment.
      Addition of tetra-N-methylammonium cation as ion-pairing agent to a methanol
      sulfuric acid-water eluent increases the retention time of the anionic SPS2- on a
      C18 column sufficiently to separate this compound from Cu(II) ion and additive by
      products.

PMID- 16106863
TI  - Study of the selectivity of inorganic anions in hydro-organic solvents using
      indirect capillary electrophoresis.
AB  - In capillary electrophoresis (CE) analysis of small inorganic anions, the ability
      to control the electroosmotic flow (EOF) and the ability to alter the
      electrophoretic mobility of the ions are essential to improve resolution and
      separation speed. In this work, a CE method for separation of small inorganic
      anions using indirect detection in mixed methanol/water buffers is presented. The
      suitability of different UV absorbing probes commonly used for indirect detection
      including chromate, iodide, phthalate, benzoate, trimellitate, and pyromellitate,
      in mixed methanol/water buffers is examined. The effect of the electrolyte buffer
      system, including the pH, buffer concentration and the organic solvent on the
      electrophoretic mobility of the probes and analytes are also investigated. The
      EOF was reversed using cationic surfactant, cetyltrimethylammonium bromide (CTAB)
      so ions were separated under co-EOF mode. The organic solvent alters the
      electrophoretic mobility of the probes and the analytes differently and hence
      choice of the appropriate probe is essential to achieve high degree of detection
      sensitivity. Separations of six anions in less than 2.5 min were accomplished in
      buffers containing up to 30% MeOH. Adjustment of the methanol content helps to
      improve the selectivity and resolution of inorganic anions. Limit of detection,
      reproducibility and application of the method for quantification of anions in
      water samples will also be discussed.

PMID- 16106864
TI  - Utilisation of crown ethers in microemulsion electrokinetic chromatography for
      the separation of inorganic cations.
AB  - A new method to influence the separation selectivity of inorganic cations in
      capillary electrophoresis is presented. This method combines the use of certain
      crown ethers to form complexes with a specific cation (changing its ionic
      radius/charge ratio and thereby its electrophoretic mobility) with partitioning
      of the crown ether/analyte complex between an aqueous phase and a pseudo
      stationary phase, such as the oil droplet of a microemulsion. Several
      microemulsions, including uncharged oil droplets and oil droplets with different
      degrees of surface charge were tested to evaluate their ability to improve the
      separation of the selected analytes.

PMID- 16106865
TI  - Ion association with alkylammonium cations for separation of anions by capillary
      electrophoresis.
AB  - A background electrolyte (BGE) containing a 100 mM concentration of an
      alkylammonium cation with ethyl, propyl or butyl groups provides an excellent
      medium for separation of anions by capillary electrophoresis (CE). Two major
      effects were noted. Use of one of a series of alkylammonium cations in the BGE at
      a selected pH provides a simple and effective way to vary and control
      electroosmotic flow (EOF) over a broad range. It is believed that the
      alkylammonium cations are coated onto the capillary surface through a reversible
      dynamic equilibrium. Secondly, alkylammonium cations modify the electrophoretic
      migration of sample anions and the electroosmotic migration of neutral organic
      analytes by association interaction. This selective interaction results in
      improved anion separations and permits the simultaneous separation of neutral
      analytes. The degree of association interaction varies with the bulk and
      hydrophobicity of the alkylammonium cations. Incorporation of an aliphatic amine
      salt of moderate molecular weight in the running electrolyte provides a valuable
      new way to vary the migration times of sample anions and to optimize their
      resolution. The interactions between alkylammonium cations and sample anions or
      neutral organics appear to take place entirely within the liquid phase and do not
      require a polymeric or micellar pseudo phase.

PMID- 16106866
TI  - [Accidental ingestion of caustic in childhood].

PMID- 16106867
TI  - [Weight, height and cranial circumference in children from "Ille-et-Vilaine":
      immaturity and hypotrophy].

PMID- 16106868
TI  - [Rotavirus gastro-enteritis in infants].

PMID- 16106869
TI  - [Dehydratation secondary to infantile acute diarrhea. Physiologic basis and
      management of parenteral rehydration].

PMID- 16106870
TI  - [Familial translocation t (16;19) (q24;q11) and birth of a girl with a trisomy
      18].

PMID- 16106871
TI  - [Hereditary chronic pancreatitis: an autosomal dominant disease].

PMID- 16106872
TI  - [Observation of an early ante and neo-natal hematuria].

PMID- 16106873
TI  - [Duhring's and coeliac's diseases].

PMID- 16106874
TI  - [A clinical study of the megallic ester of phenylbutazone in infections in
      children].

PMID- 16106875
TI  - [Diffuse intestinal lymphangiectasia].

PMID- 16106876
TI  - [Pseudo-tracheomalacia and unusual aortic arch].

PMID- 16106878
TI  - [Prevention and treatment of neonatal hypoglycemia by continuous enteral
      feeding].

PMID- 16106877
TI  - [Therapeutic failure of ampicillin during meningococcal meningitis].

PMID- 16106879
TI  - [Trisomy 22. A new case].

PMID- 16106880
TI  - [Anaylsis of 29 cases of severe Rhesus isoimmunization requiring artificial
      ventilation (1971-1973)].

PMID- 16106881
TI  - [Septicemia and meningitis in the newborn. Circumstances of onset and
      bacteriological results in 214 cases].

PMID- 16106882
TI  - [Clinical and ultrastructural study of a case of congenital myopathy with
      multiple foci].

PMID- 16106883
TI  - [Anencephaly. Epidemiological study].

PMID- 16106884
TI  - [Purulent meningitis in children with sickle cell anemia. Report of 47 cases].

PMID- 16106885
TI  - [Audio-visual method in speech therapy].

PMID- 16106886
TI  - [Transfer of high-risk neonates. Analysis of 749 cases].

PMID- 16106887
TI  - [Hemostasis disturbances in premature infants with respiratory distress.
      Influence of the severity of the distress].

PMID- 16106888
TI  - [Modification of coagulation factors during neonatal exchange transfusions].

PMID- 16106889
TI  - [Value of respiratory physiotherapy in the treatment of hyaline membrane disease
      in the newborn].

PMID- 16106890
TI  - [Urinary excretion of ampicillin in premature and small-for-gestational-age full
      term neonates].

PMID- 16106891
TI  - [Thanatophoric dwarfism. A anatomo-clinical case].

PMID- 16106892
TI  - [A case of complete triploidy (69,XXY) in a premature infant. Presence of a
      clinical syndrome characteristic of this chromosome abnormality].

PMID- 16106893
TI  - [Two cases of cyclopia].

PMID- 16106894
TI  - [Acute hemorrhagic edema of the skin in an infant. Clinical and nosological study
      . Report of three cases].

PMID- 16106895
TI  - [Nosological study of true hermaphroditism and mixed and asymmetric gonadal
      dysgenesis].

PMID- 16106896
TI  - [Association of chronic tubulointerstitial nephropathy and Saethre-Chotzen
      syndrome. A family case].

PMID- 16106897
TI  - [Posterior and bilateral congenital dislocation of the radial head. A family
      case].

PMID- 16106898
TI  - [Acute encephalopathy during treatment of lymphoblastosis in children].

PMID- 16106899
TI  - [Rickets. A rare complication of anti-epileptic treatments. Report of two cases
      in children].

PMID- 16106900
TI  - [Summer treatment at the seaside center in Roscoff for children with cystic
      fibrosis].

PMID- 16106901
TI  - [Feminising adrenal cortex tumour in children. Study of a case and review of
      literature].

PMID- 16106902
TI  - [Posttraumatic stress disorder (PTSD)].
AB  - The diagnosis of posttraumatic stress disorder (PTSD) has been introduced in
      1980. The diagnosis, as construct raises several political, moral, legal, and
      compensation issues. PTSD is considered as a multisystemic dysregulation,
      involving the hypothalamic- pituitary - adrenal axis, adrenergic
      hypersensibility, and serotonergic dysfunction. The prevalence of PTSD is 1-9% in
      the general population, but substantially higher among victims of traumatic
      events: 19-70%. Placebo controlled studies provide a body of evidence concerning
      efficacy of selective serotonin reuptake inhibitors in the treatment of PTSD both
      in the acute and maintenance treatments. Studies with balanced male-female ratio
      suggest no gender-related differences in the clinical response, furthermore both
      civilians and veterans improved significantly for selective serotonin reuptake
      inhibitor treatment.

PMID- 16106903
TI  - [Nitroglycerin-induced headaches].
AB  - INTRODUCTION: Headache is the most prominent side effect of nitrate therapy. Lack
      of compliance is usually associated with headache which has a detrimental effect
      on quality of life. In spite of the high frequency of this adverse effect, the
      headache characteristics, timing and risk factors are less known. On the other
      hand, intravenously administered nitroglycerin-induced migraine attack is a
      common human research model in migraine. AIM OF THE PRESENT STUDY: to evaluate
      the headaches occurring after administration of therapeutic dose of sublingual
      nitroglycerin, in migraineurs and controls. METHOD: Twenty-eight female migraine
      patients without aura and 14 healthy controls received 0.5 mg nitroglycerin.
      Headache intensity and characteristics have been investigated for 24 hours.
      RESULTS: two types of headache developed after the nitroglycerin administration:
      (1) an immediate headache that does not fulfil the criteria for migraine, mild
      and disappears spontaneously within 1 hour; (2) a typical migraine attack without
      aura develops several hours after the nitroglycerin administration (mean latency:
      250 min), moderate or severe, and warrants antimigraine therapy. The two types of
      headache developed independently. The nitroglycerin-induced headaches have not
      been determined solely by the previous migraine diagnosis, although both
      immediate (p = 0.0045) and typical migraine headache (p = 0.00047) were
      significantly more frequent among migraineurs compared to controls. Moreover,
      those control subjects who experienced migraine attacks had predispositions to
      migraine. Previous results of the authors supported that lower platelet serotonin
      concentration and higher plasma CGRP concentration, during the headache free
      period, are risk factors that express greater susceptibility to develop both
      spontaneous and nitroglycerin-induced migraine attack. CONCLUSION: Authors
      suggest an accurate exploration of the headache case-history before nitroglycerin
      treatment. This makes it possible to give proper information to migraine patients
      and possible migraine patients, and thus suitable treatment can be offered if
      needed.

PMID- 16106904
TI  - [Molecular mechanisms of cancer cachexia].
AB  - Molecular mechanisms of cancer cachexia. Cancer cachexia is a complex,
      multifactorial syndrome characterised by a critical weight loss, anorexia,
      asthenia and anaemia. Most of the patients with advanced cancer suffer from
      cancer cachexia. The cachectic state is closely associated with progressive
      expansion of the tumour and leads to a malnutrition status due to the induction
      of anorexia and decreased food intake. In addition, the competition for nutrients
      between the tumour and the host leads to malnutrition state, too, which promotes
      severe metabolic disturbances in the host, including hypermetabolism which leads
      to an increased energetic inefficiency. Although, the search for the cachectic
      factors has a long history, we are still far away from knowing the complete
      answer. The main aim of the present paper is to summarise the different catabolic
      mediators involved in cancer cachexia. Better understanding of the pathomechanism
      of cancer cachexia can lead to the discovery of new, effective strategies of the
      therapy for the future.

PMID- 16106905
TI  - [Successful surgical correction of tetralogy of Fallot and pulmonary atresia in
      adulthood after reconsidering inoperability].
AB  - A 36 year old male with tetralogy of Fallot and pulmonary atresia was corrected
      successfully. Previous palliative operation (Cooley shunt) was performed 35 years
      before. He was in NYHA functional class III. because of chronic hypoxia,
      polyglobulia, cerebral accident, pulmonary complications, myocardial
      (ventricular) dysfunction and syncopes. After an uneventful surgical
      reconstruction, the postoperative period was complicated with haemostasis
      complication and pulmonary distress syndrome. He left the hospital in NYHA
      functional class I on the 20th postoperative day in very good condition.
      CONCLUSION: Complete cardiac recovery will be possible after successful
      surgically reconstruction of tetralogy of Fallot and pulmonary atresia even in
      adulthood. The reconsideration of operability of such cases is recommended. As
      the patient may have different extracardiac complications in every case new
      complete reconsideration is necessary for the indication of surgical
      reconstruction.

PMID- 16106906
TI  - [Pathogenesis, symptoms and therapy of type-1 diabetes mellitus].

PMID- 16106907
TI  - [The first book on rheumatology written in Hungarian, by Ede Weisz, is hundred
      years old].

PMID- 16106908
TI  - [Thoughts regarding the Hungarian medical language and terminology].

PMID- 16106909
TI  - Dynamic properties of germ line-specific lamin B3: the role of the shortened rod
      domain.
AB  - The mammalian lamin B2 gene codes for two proteins, the somatic lamin B2 and the
      germ line-specific lamin B3. Lamin B3 lacks the N-terminus and a part of the
      alpha-helical rod domain present in lamin B2. These domains are substituted by 84
      amino acids unique for lamin B3. When ectopically expressed in somatic cells,
      lamin B3 causes severe deformation of nuclei which adopt a hook-like
      configuration. Accordingly, it was proposed that lamin B3 provides the germ line
      cells with a more flexible nuclear periphery that facilitates spermatogenesis
      specific nuclear reorganization events. Here we investigated which protein
      domains of lamin B3 are responsible for nuclear deformation in transfected cells,
      and how stable is the nuclear periphery of these cells. Expression of wild-type
      and mutant lamins evidenced that nuclear deformations are due to the shortened
      rod domain of lamin B3. Cell fractionation experiments revealed that lamin B3 can
      be solubilized more easily than lamin B2. Fluorescence recovery after
      photobleaching (FRAP) and fluorescence loss in photobleaching (FLIP) analyses of
      transfected cells showed that lamin B3 has an increased mobility compared to B2.
      Our results lead to the conclusion that lamin B3 reduces the stability of the
      nuclear periphery. They are also consistent with the notion that lamin B3 is
      relevant to specific properties of the nuclear envelope during spermiogenesis.

PMID- 16106910
TI  - Multicellular structures developing during maize microspore culture express
      endosperm and embryo-specific genes and show different embryogenic
      potentialities.
AB  - During maize pollen embryogenesis, a range of multicellular structures are
      formed. Using different approaches, the "nature" of these structures has been
      determined in terms of their embryogenic potential. In situ molecular
      identification techniques for gene transcripts and products, and a novel cell
      tracking system indicated the presence of embryogenic (embryo-like structures,
      ELS) and non-embryogenic (callus-like structures, CLS) structures that occurred
      for short periods within the cultures. Some multicellular structures with a
      compact appearance generated embryos. RT-PCR and fluorescence in situ
      hybridization (FISH) with confocal microscopy techniques using specific gene
      markers of the endosperm (ZmESR2, ZmAE3) and embryo (LTP2 and ZmOCL1, ZmOCL3)
      revealed "embryo" and "endosperm" potentialities in these various multicellular
      structures present in the cultures. The results presented here showed distinct
      and specific patterns of gene expression. Altogether, the results demonstrate the
      presence of different molecules on both embryonic and non-embryonic structures.
      Their possible roles are discussed in the context of a parallel between
      embryo/endosperm interactions in planta and embryonic and non-embryonic structure
      interrelations under in vitro conditions.

PMID- 16106911
TI  - Endogenous expression of liver-specific drug transporters for organic anions in
      the rat hepatocytoma fusion cell line HPCT-1E3.
AB  - HPCT-1E3 cells, a fusion cell line between primary rat hepatocytes and Fao Reuber
      hepatoma cells H35, are immortalized hybrid cells with many phenotypic properties
      of liver parenchyma including phase I and II metabolism and bile acid secretion.
      Selective elimination of endogenous compounds and drugs by the liver involves
      transport proteins that complementarily mediate uptake and efflux in co-operation
      with metabolism, but the study of this function is limited by the unavailability
      of an integrated in vitro model. Therefore, we investigated the expression of
      some important liver-specific import and export carrier proteins for organic
      anions in this cell line. RT-PCR analysis indicated gene expression of Oat2,
      Oatplal, Oatpla4, Oatplb2, Rfc-1/MTX-1, FOLR, Mrp1-6, mdr1, and Lrp. Uptake and
      efflux as well as inhibition studies confirmed the functional activity of Oat,
      Oatp, Rfc-1, Mrp, and Mdr carriers. In conclusion, the hepatocyte-like HPCT-1E3
      cell line shows endogenous expression of all liver-specific carrier proteins for
      organic anions and may hence represent a valuable in vitro model for the study of
      transport phenomena and their regulation in hepatocytes.

PMID- 16106912
TI  - H2O2 induces paracellular permeability of porcine brain-derived microvascular
      endothelial cells by activation of the p44/42 MAP kinase pathway.
AB  - In vivo, pathological conditions such as ischemia and ischemia/reperfusion are
      known to damage the blood-brain barrier (BBB) leading to the development of
      vasogenic brain edema. Using an in vitro model of the BBB, consisting of brain
      derived microvascular endothelial cells (BMEC), it was demonstrated that hypoxia
      induced paracellular permeability was strongly aggravated by reoxygenation (H/R),
      which was prevented by catalase suggesting that H2O2 is the main mediator of the
      reoxygenation effect. Therefore, mechanisms leading to H2O2-induced
      hyperpermeability were investigated. N-acetylcysteine and suramin and furthermore
      usage of a G protein antagonist inhibited H202 effects suggesting that activation
      of cell surface receptors coupled to G proteins may mediate signal initiation by
      H2O2. Further, H2O2 activated phospholipase C (PLC) and increased the
      intracellular Ca2+ release because U73122, TMB-8, and the calmodulin antagonist
      W7 inhibited H2O2-induced hyperpermeability. H2O2 did not activate protein kinase
      C (PKC), nitric-oxide synthase (NOS), and phosphatidyl-inositol-3 kinase (PI3
      K/Akt). Inhibition of the extracellular signal-regulated kinase (ERK1/ERK2 or
      p44/42 MAPK), but not of the p38 and of the c-jun NH2-terminal kinase (JNK),
      inhibited hyperpermeability by H2O2 and H/R completely. Corresponding to H2O2-
      and H/R-induced permeability changes the phosphorylation of the p44/42 MAP kinase
      was inhibited by the specific MAP kinase inhibitor PD98059 and by TMB-8 and W7.
      Paracellular permeability changes by H2O2 correlated to changes of the
      localization of the tight junction (TJ) proteins occludin, zonula occludens 1 (ZO
      1), and zonula occludens 2 (ZO-2) which were prevented by blocking the p44/p42
      MAP kinase activation. Results suggest that H2O2 is the main inducer of H/R
      induced permeability changes. The hyperpermeability is caused by activation of
      PLC via receptor activation leading to the intracellular release of Ca2+ followed
      by activation of the p44/42 MAP kinase and paracellular permeability changes
      mediated by changes of the localization of TJ proteins.

PMID- 16106913
TI  - How to work up hematuria of unknown origin?

PMID- 16106914
TI  - Osteomyelitis in diabetic foot ulcers. Prompt diagnosis can avert amputation.
AB  - Osteomyelitis is a prevalent sequela of diabetic foot ulcers. The timing of its
      diagnosis and treatment is crucial if the diabetic patient is to avoid amputation
      later. However, detection of this condition can be difficult in the primary care
      setting. Information gained by physical examination and sequential imaging
      methods is central to identification of osteomyelitis in its beginning stages.
      Here, Drs Schinabeck and Johnson review the clinical, laboratory, and radiologic
      findings critical to making an early diagnosis of osteomyelitis.

PMID- 16106915
TI  - Taking a proactive approach to physician impairment.

PMID- 16106916
TI  - Prescription drug use and abuse. Risk factors, red flags, and prevention
      strategies.
AB  - When a patient is in physical or emotional pain, prescribing controlled
      substances often appears to be the simplest and most efficient way to relieve
      suffering and distress. However, in a minority of cases, this approach leads to
      prescription drug abuse and patient harm. In this article, the authors review the
      epidemiologic factors of prescription drug abuse, legal policies designed to
      safeguard against it, risk factors and red flags, and practical ways to minimize
      the chances of misuse.

PMID- 16106917
TI  - Pathologic gambling disorder. How to help patients curb risky behavior when the
      future is at stake.
AB  - Pathologic gambling disorder and problem gambling are becoming increasingly
      common in the United States as more states legalize gambling. Although gambling
      related disorders can cause devastating consequences, well-studied treatments are
      few. Fortunately, clinical experience suggests that pathologic gambling disorder
      is highly treatable. In this article, Drs Sumitra and Miller briefly summarize
      gambling-related disorders and discuss available, effective treatments.

PMID- 16106918
TI  - Managing insect sting allergy. The ins and outs of venom immunotherapy.
AB  - Insect sting allergy can lead to severe, even fatal, reactions in susceptible
      persons. Although self-injection epinephrine often terminates the reaction, it is
      not always effective. In this article, Dr Graft explores the use of venom
      immunotherapy (VIT) in selected patients in whom successful treatment can produce
      psychosocial as well as physiologic benefits.

PMID- 16106919
TI  - Visual disturbance after traumatic femur fracture.

PMID- 16106920
TI  - Patient notes. Heel spur.

PMID- 16106921
TI  - Testosterone supplementation in the aging male: which questions have been
      answered?
AB  - PURPOSE: There is no consensus on possible benefits and risks of testosterone
      supplementation. Here we review various controlled studies of testosterone
      supplementation in aging males. METHODS: We performed a PubMed search using the
      terms "testosterone/therapeutic use" with the limits " > 65 years of age",
      "randomized controlled clinical trials", and "male gender", starting in 1999.
      RESULTS: Forty-three articles have been published since 1999. Some of these
      studies also included patients in middle-age or younger. Findings reported in
      these articles were not entirely consistent. After weighting studies by the
      number of patients, hints are found that testosterone supplementation increases
      bone mass, lean body mass, muscle mass and hematopoiesis, and improves sexual
      functioning and perhaps mood, but does not affect serum lipids, cardiovascular
      parameters, prostate-specific antigen level, or cognition. Considering studies
      including only men older than 65 years, and in which testosterone supplements
      were compared with placebo treatment, slightly different results are obtained. In
      these patient groups, testosterone does not improve sexual function or mood.
      CONCLUSION: The overall benefit of testosterone supplementation for the aging
      male remains unclear. Any supplementation in men with age-normal testosterone
      levels only on grounds of subjective symptoms is not advisable.

PMID- 16106922
TI  - The epidemic of obesity: obesity and health of the aging male.

PMID- 16106923
TI  - The aging male in African ethnic cultures.

PMID- 16106924
TI  - The lexicon of the "old age" in the classical languages: between history and
      etymology.

PMID- 16106925
TI  - [Ernest Juvara (1870-1933)].

PMID- 16106926
TI  - [Centenary--Theodor Burghele].

PMID- 16106927
TI  - [Thoracoscopic thymectomy in the treatment of myasthenia gravis].
AB  - A series of 151 thoracoscopic thymectomy performed in the Department of General
      Surgery and Liver Transplantation of the Fundeni Clinical Institute between April
      1999 and April 2004 is analyzed. These were 89.34% from all the thymectomies
      performed in our department in this period. Thoracoscopic thymectomies were
      performed on 131 female patients (86.75%) and 20 male patients (23.25%), aged
      between 8 and 60 years. All patients were previously treated in the Neurological
      Department of the Fundeni Clinical Institute for at least 3 months. The
      thoracoscopic thymectomy was indicated for: myasthenia gravis without thymic
      neoplasia (141 cases), stage I Masaoka thymoma (8 cases), remnant postoperative
      thymic tissue (3 cases). We have used a left thoracoscopic approach in 73 cases
      and a right thoracoscopic approach in 76 cases. In 2 cases a mixed cervical and
      thoracoscopic approach was needed.. No mortality and morbidity 6.62% (10 cases).
      From this 151 patients 100 have been constantly followed for more then one year.
      From the other 51, 32 are in the first postoperative year, and the other 19,
      12.58% have been lost in surveillance. The one year evaluation regarding the
      Research Standards of Myasthenia Gravis Task Force Foundation shows: improvement-
      90% (complete stable remission--14%; pharmacological remission--20%; minimal
      manifestation--56%), unchanged--8%, worsened--2%. Our results with a complete
      stable remission of 14% at the end of the first year and 50% at 5 years are at
      least comparable with literature results with other open or thoracoscopic
      approaches.

PMID- 16106928
TI  - [Long-term prognostic value of positive peritoneal washing in colon cancer].
AB  - We examined the prognostic value of free malignant cells in the peritoneal cavity
      of patients with colon adenocarcinoma. In 1996-1999, 88 patients underwent
      peritoneal washing with cytologic analysis immediately before elective colon
      resection for adenocarcinoma with no evidence of peritoneal metastases.
      Peritoneal washing fluid was collected before abdominal exploration centrifuged
      immediately and stained with the May-Grunwald-Giemsa and Harris-Shorr methods.
      Malignancy was defined as recommended by Papanicolaou. Free malignant cells in
      peritoneal fluid were found in 25 of 88 (28%) patients (Dukes A 0, of 11, Dukes B
      10 of 31, Dukes C 11 of 37, Dukes D 4 of 9). The positive rate was 24 of 75 (32%)
      among patients with tumors involving the serous layer and 1 of 13 (8%) among the
      others (p = 0.00989). Positive peritoneal washing was not significantly
      associated with survival in multivariate analysis. CONCLUSION: The presence of
      free malignant cells in the peritoneal cavity of patients with colon cancer
      provided no further prognostic information relative to the Dukes classification
      in this study. The 5 years survival rates were 48% among patients with positive
      and negative peritoneal washing respectively (p = 0.09).

PMID- 16106929
TI  - [Surgical strategy in laparoscopic repair of hiatal hernia and procedures for
      gastroesophageal reflux].
AB  - The authors discuss about 68 celioscopy antireflux procedures, carried out for
      transhiatal hernia accompanied by gastroesophageal reflux, during a period of 8
      years, between 1996 and 2003. The aim of this research is a clinical and
      technical comparative study, in fact between the posterior total or partial
      fundoplication and the anatomical procedures. In order to have a complete
      evaluation of the risks and results, the authors discuss the indications of each
      procedure, a series of specific intra and postoperative complications, including
      conversions and reinterventions, for each procedure. The authors also refer to
      the difficulty degree, the time required for each procedure, to find out the ways
      of improving these parameters. Although the number of patients is quite small, in
      this experience, posterior fundoplication seems easier and safer, whenever
      possible. The Nissen procedure, which technique is more laborious, seems to offer
      a better postoperative evolution and more long - lasting results in time.

PMID- 16106930
TI  - [A possible protocol for postoperative management in laparoscopic
      cholecystectomy].
AB  - The goal of the "Prospect" programme (sponsored by Pfizer) is to create possible
      evidence-based protocols related to the management of postoperative pain after
      certain type of surgical intervention (e.g. hernia repairs, hysterectomies,
      etc.). This article is introducing the protocol for laparoscopic cholecystectomy
      for both day-case and longer hospital admission cases. The protocol is designed
      for preoperative, intra and postoperative period, choosing only those measures
      which were effective for postoperative pain, published in the literature. We are
      also presenting an analyze of our 13,000 laparoscopic cholecystectomies, from
      "Prospect" protocol point of view, and what we should do to improve the
      management of postoperative pain.

PMID- 16106931
TI  - [Surgical strategy in the management of benign obstructive jaundice].
AB  - 623 patients with benign biliary obstructions of extrahepatic biliary ducts were
      treated in surgical clinic number 2 during the period of 1990-2002 years.
      Surgical treatment included 3 stages: (1) diagnosis of benign biliary
      obstructions; (2) preoperative biliary tree decompression; (3) definitive
      surgical resolve. Definitive diagnosis was established in 90% of cases after
      cholangiopancreatography retrograde endoscopic (CPGRE), in 7% of cases was used
      cholangiography transhepatic percutaneous with using ultrasonography, which was
      the method of choice in cases with high obstructions, and with gastric resections
      in anamnesis. In 22 cases with negative results of applied methods was used MRI
      of biliary tract, with permitted positive solution of problem. Surgical tactics
      was in direct dependency from pathology, level of obstruction, grade of clinical
      manifestation of the disease. In all cases was applied staged treatment, with
      permitted in pre-operative period to resolve the jaundice, biliary infection and
      correction of hepatic function with following surgical definitive correction with
      minimal risk of postoperative complications. The total lethality was 9 (1.44 %)
      patients.

PMID- 16106932
TI  - [Lower limb varicosity in patients, with indication for total knee arthroplasty].
AB  - Preoperative treatment of the peripheral venous pathology in patients with
      indication for total knee arthroplasty (TKA) would reduce the risk of
      postoperative deep venous thrombosis (DVT). Between 1997 and 2004, 110 patients
      were evaluated for TKA. 35 had also varicose veins in the lower limbs. 4 patients
      were excluded because of absolute contraindications for surgery. 31 patients
      presented varicose disease, in different stages according with CEAP. The patients
      were treated surgically (Babcock or Muller technique), phlebotomy drugs and
      mechanical contention. In a single case the TKA was done without any preoperative
      treatment of the varicosities. TKA was done after 8-12 weeks. DVT prophylactic
      measures were undertaken in all 95 cases. Results were good except 2 cases of DVT
      and 1 case or pulmonary embolism in patients with preoperative treatment of the
      venous disease. The patient with no preoperative treatment of its varicose veins
      developed DVT with chronic, persistent oedema. Preoperative treatment of the
      varicose veins in the lower limb is mandatory for a successful TKA.

PMID- 16106933
TI  - [Treatment of cardiac stab wounds. A thirty-one-year experience].
AB  - Penetrating cardiac wounds represent a dramatically pathology of the general
      surgery because of their clinical presentation and outcome. The cardiorrhaphy
      with the three successive times, carried out with maximum rapidity is the only
      safe and efficient surgical technique which leads to hemostasis and healing. The
      aim of this study was to evaluate our results and experience of penetrating
      cardiac injuries treated at the Clinic of Surgical Emergencies from Iasi. 20
      patients, 17 men and 3 women, of mean age 34 years (range 18-51), with stab
      wounds, underwent cardiorrhaphy between 1974 and 2004. The clinical aspects were:
      "white injured" (hemorrhagic shock) in 3 patients, "blue injured" (cardiac
      tamponade) in 8 patients, both being implied with some patients, one of the
      aspects being predominant. 9 patients (45%) had only cardiac injuries and 11
      (55%) had other associated injuries. There were 7 intraoperative cardiac arrests
      and 2 postoperative pulmonary complications. In 16 cases the outcome of patients
      with cardiac stab wounds was favourable. We recorded 4 deaths. Mortality results
      from the wounds of the right auricle. The high rate of survival (80%) proves that
      a penetrating cardiac injury with a heavy prognosis may be turned into a relative
      traumatism harmless for those patients who will remain alive until they arrive in
      hospital.

PMID- 16106934
TI  - [The reconstruction of the oral and maxillofacial defects with free vascularized
      flaps and microsurgical anastomoses].
AB  - The reconstruction of the oral and maxillofacial defects is difficult, because of
      the high specialisation of the tissues. In cancer resection, the post-operatory
      defects are quite important, because of the oncological principle of assuring
      free margins. The free flap is a modem and nowadays very used method in oral and
      maxillofacial reconstruction, after the removal of the malignant tumors with this
      localisation. These flaps are indicated for large defects, when the
      reconstruction with local or regional flaps is not possible. The wide variety of
      the raised tissues allows better results, making them the flaps of choice for
      large defects of the lip and cheek. The main advantages are related to the tri
      dimensional extension of the free margins, assuring the quality of life and
      allowing early initiation of the radiotherapy in oncological patients.

PMID- 16106935
TI  - [Dupuytren disease. Experience at the Clinic of Plastic Surgery, Clinical
      Emergency Hospital "Bagdasar-Arseni"].
AB  - This work is studying the pathogenic concepts about Dupuytren disease. A lot of
      theories and assumptions have been put forward around this disease, but none of
      them could explain the real etiopathogenic conditions. Doctor Chiotan (1999) was
      saying that if we don't have an objective, integrated concept, it doesn't mean
      that we don't have ideas, theories. We call this ideology. We want to present, by
      turn, the tumoral theories about Dupuytren disease, the healing and inflammatory
      theories, the neurovascular theory, the intrinsic and extrinsic theories.

PMID- 16106936
TI  - [Left hepatic lobectomy].

PMID- 16106937
TI  - [Severe nosocomial infection of soft tissue in general surgery].
AB  - This paper aim is to emphasize the severity of soft tissue nosocomial infections,
      determined by anaerobic bacteria associated with Gram-negative aerobic bacteria:
      50% mortality, higher economic costs, disabling morphologic and functional
      sequels. We present the pathogenic, clinical and therapeutically problems which
      characterize this type of postoperative infections.

PMID- 16106938
TI  - [Pulmonary embolism--complication of proximal deep venous thrombosis in
      colorectal cancer. Diagnosis and management].
AB  - We present the case of a 57 years old male, without cardiovascular history, with
      colorectal cancer and proximal deep venous thrombosis, who develops a massive
      pulmonary embolism. The surgical treatment consists in embolectomy of right
      ventricle, pulmonary trunk, left and right pulmonary artery. The specifics of the
      case is discussed: etiology and prevention of pulmonary embolism (caval filter)
      and treatment: the contraindications of thrombolytic therapy and the indications
      and perspectives of surgical treatment.

PMID- 16106939
TI  - [Emphysematous necrotizing pancreatitis].
AB  - The authors present an additional case of emphysematous necrotizing pancreatitis
      caused by Escherichia coli. Emphysematous necrotizing pancreatitis represents a
      rare and potentially life-threatening infection and is characterized by gas
      formation within or around the pancreas. A 26-year-old man presented with severe
      upper abdominal pain and vomiting, 7 hours from onset. Acute pancreatitis was
      initially diagnosed based on high amylase level, abdominal ultrasonography and
      primary CT scan. On the 7th day he developed fever, increasing abdominal pain and
      shortness of breath. On the second abdominal CT scan, the pancreatic bed was
      filled with gas. The diagnosis of emphysematous necrotizing pancreatitis was
      confirmed at laparotomy. The patient was treated successfully by extensive
      pancreatic necrosectomy, open packing and scheduled repeated debridements.
      Culture from the lesser sac, and retroperitoneal space, examined for aerobes and
      anaerobes, revealed growth of Escherichia coli. The authors analyze and discuss
      pathogenesis, diagnosis and treatment of emphysematous necrotizing pancreatitis.
      Based on the available data and this case, early surgical debridement and
      appropriate antibiotics appear to be the preferred treatment.

PMID- 16106940
TI  - [Endosalpingiosis of the axillary lymph nodes--primary or metastatic tumour?].
AB  - The involvement of extra-abdominal sites by serous ovarian tumours of low
      malignant potential is extremely rare. In this paper we present the case of a 33
      years old woman, diagnosed with atypical endosalpingiosis in the axillary lymph
      nodes before the diagnosis of a bilaterally ovarian serous tumour of low
      malignant potential. The occurrence of axillary lymph nodes involvement
      associated with serous tumours of the ovary could be explained by the presence of
      circulating serous cells that remained dormant for a period of time or by the
      development of an independent primary tumour from glandular inclusions in
      axillary lymph nodes. The recognition of the occurrence of axillary atypical
      endosalpingiosis in association with serous tumours of the ovary is important to
      avoid misdiagnosis. It is better to define these lesions as secondary serous
      papillary involvement.

PMID- 16106941
TI  - [7th Symposium and post-university course of the Romanian Section of the
      International Association of Surgeons and Gastroenterologists].

PMID- 16106942
TI  - Unannounced survey takes its toll on ED--will you be ready when it's your turn?
AB  - The new era of Joint Commission on Accreditation of Healthcare Organizations
      surveys requires an extra measure of preparation, as well as a refresher course
      on how to respond if surveyors find violations in your ED. Participate in
      periodic performance reviews, and make an effort to get on your hospital's Joint
      Commission committee. If violations are found, meet with your staff. Be honest,
      and solicit their involvement in finding solutions. Overcrowding, medication
      management, and privacy will be the Joint Commission's major areas or emphasis
      during surveys.

PMID- 16106943
TI  - Tracers: they're not just for accreditation surveys.
AB  - Conducting periodic tracers will help your staff improve their performance,
      enhance communications with other hospital departments, and become more familiar
      with Joint Commission on Accreditation of Healthcare Organizations standards and
      terminology. Address specific service lines (i.e., pneumonia, stroke) to identify
      more targeted opportunities for improvement. Pay particular attention to handoffs
      and documentation when conducting your own internal tracers. Mock surveys,
      including tracers, can be valuable tools for ensuring ongoing readiness for Joint
      Commission visits.

PMID- 16106944
TI  - Do your staff know how to handle organ donations?
AB  - Make sure your staff know whom to contact and when concerning organ donation. The
      right action at the right time can avoid potential liability and ensure optimal
      communications with family members at a time of heightened emotional sensitivity.
      Staff members should be aware of clinical triggers and the different donation
      options indicated by manner of death. Develop ongoing relationships with organ
      procurement agencies, and make sure your staff know the appropriate contact at
      each agency. Having an individual other than the caregiver approach the family
      will reduce risk of legal exposure.

PMID- 16106945
TI  - Hospitals' preparation for surge of patients helps with new Joint Commission
      standards.
AB  - To meet new surge capacity accreditation standards, hospitals are looking at
      their current plans to handle a sudden influx of patients and determining what
      works well for infectious patients. Consider putting two stretchers in a room.
      Determine how to establish room numbers for the second patient's record; you can
      start numbering after the last room number on the floor. Also, the second patient
      will need a call light, room divider, and meal trays. Consider twice-a-day bed
      meetings routinely for clinical directors. Notify physicians when you need beds,
      and have case managers to assist with transportation. Bring a phlebotomist to the
      ED, and have physicians help plan care at triage.

PMID- 16106946
TI  - JCAHO preparation in a fast-paced ED.

PMID- 16106947
TI  - New tracking systems improve patient flow.
AB  - Wireless or infrared tracking systems can help you keep a handle on patient
      whereabouts, the status of tests that have been ordered, and locate important
      equipment in a more timely manner. Managers can track activities in admissions,
      lab, and pharmacy from a single location. Staff no longer has to spend time
      looking for patients, equipment, or each other. Key information is not only
      visible on a central monitor, but on every desktop computer in the ED.

PMID- 16106948
TI  - A 'Nod' to patient needs boosts satisfaction rates.
AB  - Little things like kind words, propped pillows, afternoon snacks, and follow-up
      calls can make a world of difference in how patients perceive you and your staff.
      Make sure your staff members introduce themselves to patients and explain what
      they are about to do. Make your best effort to minimize times that patients are
      hungry, angry, lonely, or tired. Seek input from patients who left without being
      seen to help avoid similar problems in the future.

PMID- 16106949
TI  - Staff, patients prefer ED-based interpreters.
AB  - Having interpreters in your ED can save time in moments of crisis, while at the
      same time, facilitating more accurate communications among staff, patients, and
      family members. Make sure interpreters are familiar with basic anatomy, major
      illnesses, and medications. Human beings can interpret glances or the touch of a
      hand, which gives them an advantage over telephonic services. Arrange for at
      least two vehicles for paging interpreters when they are needed.

PMID- 16106950
TI  - [Estimation of local fraction of cardiac output in the view of the active
      diastole theory].
AB  - Is shown, that as against single-phase model of pulse hemodynamics (the theory of
      passive diastole), the expression of pulse component in formula of definition of
      stroke volume on chest rheography explains satisfactorily in the view of two
      phase model (the theory of active diastole). The new original rheographic index
      of blood supply of a studied vascular zone--local fraction of cardiac output is
      offered. Calculation of the given parameter has much in common with calculation
      of quantitative definition with pulse component of stroke volume, but is
      calculated under more simple formula and can practically be used for any site of
      cardiovascular system.

PMID- 16106951
TI  - [On the method of express-diagnostics of thyroid gland dysfunctions].
AB  - The method of express-diagnostics of thyroid diseases on a degree of moisture of
      the skin integument which is one of clinical attributes of hypothyroidism (a skin
      is dry, shelled, with sites of keratinization) and hyperthyroidism at which the
      return picture is observed, i.e. the (increased humidity of a skin is offered. At
      the same time as a parameter describing a degree of moisture of skin is a
      relative humidity of the air environment which are taking place above the skin
      integument in conditions of thermodynamic equilibrium. The instrument is a
      hermetic glass in which the sensor of humidity is mounted. Studies on the
      definition of threshold levels of parameter for several groups of patients with
      clinically confirmed diagnoses of diseases of a thyroid are carried out.

PMID- 16106952
TI  - [Effective radiation doses of the personnel at rentgenosurgical studies].
AB  - In the paper versatile study of radiation dose of the medical personnel is
      carried out at rentgenosurgery with application of tissue-equivalent phantoms.
      For the first time spectrometric study of dissipated radiation by object is
      carried out, normalized to unit of exposition dose fields around of the object
      are constructed.

PMID- 16106953
TI  - [Automated system for study of mechanical properties of the organs and tissues on
      the basis of the apparatus for resonance vibrotherapy "Landysh"].
AB  - The measuring-calculating system uniting the system for resonant vibrotherapy
      "Landysh", the analog-digital converter and computer is submitted. The system
      allows not only to carry out therapeutic action on a body tissues by vibration,
      but also to register the response of organism to this action, to supervise
      efficiency depend upon change of parameters of self-oscillations and mechanical
      characteristics of tissue. Results of study of influence of resonant vibrotherapy
      on posttraumatic hypostases of soft tissues in patients with consequences adnate
      fractures are presented. The system can be used in urology and andrology for
      study of erection function in men, and also for biological tests of various
      chemical compounds in pharmacology, toxicology, dermatology and cosmetology.

PMID- 16106954
TI  - [Evolution of the automated system for preventive examination of children an
      automated unit for mass screening examinations].
AB  - The complicated situation in pediatric healthcare and long-term negative trends
      observed in the health of children predetermined the necessity of introducing
      automated units built on the principles of preventive medicine and screening
      diagnostics into the practice of healthcare. AKDO units belong to such equipment
      designed for early diversified diagnostics of chronic diseases made within
      comprehensive examinations of children, i.e. a state program of regular medical
      check-ups of children. The paper presents objective trends taking place in the
      modern practical healthcare that necessitated principle changes in and promotion
      of functional potentialities of the existing ASPON systems developed in 1983
      1988.

PMID- 16106955
TI  - [Structural analysis of diagnostic efficiency of bodyplethysmography indexes in
      patients with bronchial asthma].
AB  - In the paper the probabilistic assessment of diagnostic efficiency of
      bodyplethysmography indexes in patients with bronchial asthma instead of the
      prevailing method of comparison of mean-value is carried out. It is shown, that
      the estimation of diagnostic efficiency of body-plethysmography indexes by
      probabilistic methods in patients with bronchial asthma has advantages in
      comparison with a traditional estimation of mean-value as allows to determine the
      information density of each size from a position of probability and to improve
      functional diagnostics of this disease.

PMID- 16106956
TI  - [Instrument for biomechanical studies of soft tissues].
AB  - The instrument for study of mechanical properties of tissue, in particular for
      definition of strengthening and elastoplastic properties of stomach mucous,
      umbilical artery, skin cicatrix is offered. The instrument can find application
      for multi-purpose biomedical studies in morphology, surgery, etc.

PMID- 16106957
TI  - [Synthesis of radiological models and radiological invariants (constants). Part
      1].
AB  - Work is devoted to synthesis of mathematical models (MM) which describe
      probability of appearance of radiation complication (ARC) in a tissue at the
      Klepper's fixed scheme of dose fractionation (FD) and Ellis's MM, which describes
      equivalent schemes FD for fixed value ARC. Creation of synthesized mathematical
      models(S) appears possible at some assumptions which require a check on the basis
      of the clinical information are necessary for definition of optimum dynamic
      conditions of an radiation of cancerous growths which include the optimum
      physical radiation plan and the optimum scheme its realization in time. The
      synthesis of MM leads to natural appearance of radiological invariants
      (constants) which can become a basis for construction of a new scientific
      direction of quantitative radiology.

PMID- 16106958
TI  - [Information technologies for scanning X-ray radiography].
AB  - Digital technologies have been widely used in X-rays diagnostics, including
      computer tomography, magnetic-resonance tomography, digital radiography etc.
      Digital technologies for image analysis essentially change all arrangements and
      procedures of preventive examinations made at patient-care facilities. As for
      digital fluorography, the basic principles of fluorography diagnostic room are
      standard but for one arrangement-the unit is controlled via a computer-assisted
      working place (CAWP) by the radiologist assistant; the room of radiologist is
      also equipped with CAWP. Admittedly, a key issue in general fluorographic
      examinations is registration of patients and preparation of them for the
      procedure. Contemplated in the paper are new potentialities of digital
      fluorography of big number of patients by low-dose fluorography (LDF, equipment
      manufacturer/Orel, Russia) which enhance the rate and quality of diagnostics.

PMID- 16106959
TI  - [Hilbert transform-based modelling of EKG].
AB  - Recent developments in modeling methods on the non-linear and non-stationary
      data, such as electrocardiograms (ECG), have received large attention by the time
      frequency analysts. The technique presented in this paper is based on
      parametrical modeling of the instantaneous module as well as instantaneous phase,
      estimated directly from each ECG beat. The estimation is adaptive since, the
      parameters related to a specific ECG beat are calculated from a given reference
      signal. In order to evaluate the performance of our technique, data recorded from
      the MIT-BIH arrhythmia database are used.

PMID- 16106960
TI  - [ECG compression method by using multiple polynomial modelling: comparison with
      wavelet-changing technique].
AB  - The proposed ECG compression combined two approaches, ECG beat alignment and
      polynomial modeling. QRS complexes are firstly detected then aligned in order to
      reduce high frequency changes from beat to beat. These changes are modeled by
      means a polynomial projection. ECG from MIT-BIH database are used to evaluate the
      performances of the proposed technique. A comparison with the wavelet approach is
      performed by means the compression ratio (CR) versus the RRD curve.

PMID- 16106961
TI  - [ The experience of using the monitoring system of somatic health in students].
AB  - In the paper results of long-term exploitation of apparatuses complex of before
      doctor examination of patients for monitoring a condition of somatic health of
      students are presented. Influence of physical preparation on a state of health is
      discussed. Recommendations are given and the monitoring technique is offered on
      the basis of the received experience.

PMID- 16106962
TI  - Early developments in muscle research and the role of new structural
      technologies.

PMID- 16106963
TI  - The molecular basis of cross-bridge function.

PMID- 16106964
TI  - Molecular synchronization in actomyosin motors --from single molecule to muscle
      fiber via nanomuscle.

PMID- 16106965
TI  - Distribution of crossbridge states in contracting muscle.

PMID- 16106966
TI  - X-ray diffraction studies of striated muscles.

PMID- 16106967
TI  - Conformational change and regulation of myosin molecules.

PMID- 16106968
TI  - Driving filament sliding: weak binding cross-bridge states, strong binding cross
      bridge states, and the power stroke.

PMID- 16106969
TI  - Mysteries about amplitude and efficiency of cross-bridge powerstroke.

PMID- 16106970
TI  - Sarcomere dynamics, stepwise shortening and the nature of contraction.

PMID- 16106971
TI  - Crossbridge formation detected by stiffness measurements in single muscle fibres.

PMID- 16106972
TI  - Non cross-bridge stiffness in skeletal muscle fibres at rest and during activity.

PMID- 16106973
TI  - Nature's strategy for optimizing power generation in insect flight muscle.
AB  - Table 1 summarizes the primary mechanisms most likely responsible for modifying
      wing beat frequency (WBF) and muscle power in the Drosophila mutants discussed
      above. The different outcomes reflect different mechanisms that come into play,
      depending on the protein and site of the mutation. For example, the reduced
      muscle power and WBF of the RLC phosphorylation site mutant Mlc2(S6sA,S67A)
      reflect the reduced number of myosin heads available to form working cross
      bridges and the concomitant reduction in muscle stiffness. The mixed results of
      the other mutants are more difficult to explain. For example, while the reduced
      muscle stiffness of the paramyosin rod mutant pm(S18A) and the projectin mutant
      bent(D)/+ may in part reflect mutation-related increases in compliance of the
      thick filaments (pm(S18A)) or connecting filaments (bent(D)/+), the elevated WBF
      is unexpected because one would expect reduced muscle stiffness to lower WBF
      rather than raise it. Other aspects of the results are equally baffling. In the
      case of pm(S18A), e.g., myofilament kinetics are enhanced, opposite to what one
      would predict from reduced myofilament stiffness (Wang et al. 1999), but
      consistent with a direct effect of the mutation on cross-bridge kinetics. It is
      tempting to speculate that the fly increases the resonance frequency of its
      flight system, perhaps even over-compensating, as a mechanism for bringing the
      optimum frequency of power output of the flight system in line with the optimum
      frequency of power output of the myofilaments in order to achieve flight. The fly
      might accomplish this by voluntarily activating flight control muscles that
      change the stiffness and shape of the thoracic box (Tu and Dickinson, 1996),
      thereby significantly changing the basal stiffness of the resonance system. This
      effective strategy would serve to tune flight system kinetics to that of the
      actomyosin motor for optimum power transmission. Notably, of the four thick
      filament mutations listed in Table 1 produce no significant changes in wing beat
      frequency, three exhibit reduced muscle power, so these flies must make other
      adjustments to maintain flight competency. These may be additional cases in which
      the effects of marked changes in cross-bridge kinetics (MHC IFI-EC), cross-bridge
      deployment (Mlc2(delta2-46), or sarcomere (thick filament) stiffness (pm(S-A4)
      and Df(3L) fln(1)/+) are ameliorated by the intervention of direct flight
      muscles. In summary, it may well be that the fly's general response to mutations
      that alter one component of the flight system is to alter another in order to
      maintain optimum transmission of power and flight competency. That is, nature's
      strategy for optimizing power generation throughout the flight system is probably
      the same as that at the level of the myofibril: that is, strengthen weak links,
      orient parts for optimum power production, and modify power train proteins
      through isoform switches or post-translational modifications to assure all
      components are in tune with one another.

PMID- 16106974
TI  - From crossbridges to metabolism: system biology for energetics.

PMID- 16106975
TI  - Energetics, mechanics and molecular engineering of calcium cycling in skeletal
      muscle.
AB  - During muscle contraction and relaxation, Ca2+ moves through a cycle. About 20 to
      40% of the ATP utilized in a twitch or a tetanus is utilized by the SR Ca2+ pump
      to sequester Ca2+. Parvalbumin is a soluble Ca2+ binding protein that functions
      in parallel with the SR Ca2+ pump to promote relaxation in rapidly contracting
      and relaxing skeletal muscles, especially at low temperatures. The rate of Ca2+
      dissociation from troponin C, once thought to be much more rapid than the rate of
      relaxation, is likely to be similar to the rate of cross-bridge detachment and to
      the rate of muscle relaxation under some conditions. During the past fifty years,
      great progress has been made in understanding the Ca2+ cycle during skeletal
      muscle contraction and relaxation. Nonetheless, there are still mysteries waiting
      to be unraveled.

PMID- 16106976
TI  - Heat, phosphorus NMR and microcalorimetry in relation to the mechanism of
      filament sliding.
AB  - For muscle heat measurements the methods available are sensitive and rapid, and
      the heat is related to the chemical changes in a manner that provides a firm
      outline for understanding the mechanism of contraction. For example linear
      dependence of the shortening heat on the sarcomere length has shown that the rate
      of turnover of cross-bridges increases during shortening. However, heat is bound
      to lack specificity. In order to cope with this problem, various methods such as
      rigorous chemical analyses, phosphorus NMR and microcalorimetry have been
      introduced. As a result of ultra-rapid freezing and chemical analysis by D. R.
      Wilkie (Gilbert, Kretzchmar, Wilkie and Woledge, 1971), the energy balance
      discrepancy between (heat + work) and the amount of phosphocreatine (PCr) split
      emerged, i.e. the unexplained enthalpy. Calcium ions move from the sarcoplasmic
      reticulum to the calcium-receptive proteins in the sarcoplasm during contraction.
      In an attempt to find the cause of the unexplained enthalpy, microcalorimetry of
      calcium binding to calcium-receptive proteins has been performed. The results
      have shown that calcium ions dislocated between sites within the sarcoplasm on
      activation may produce about 1/3 of the unexplained heat. In addition calcium
      pump should operate by consuming PCr to relocate the calcium after the
      contraction. Time-resolved phosphorus NMR has also shown that a certain amount of
      PCr splitting continues during early minute of recovery period after the
      contraction without Pi released. This delayed splitting of PCr is most likely
      caused by the kinetic properties of the contractile proteins and can explain
      another 1/3 of the unexplained enthalpy. The mechanism of how muscle is regulated
      is another important question. Studies of calcium binding to calcium-receptive
      proteins in the sarcoplasm by using titration microcalorimetry has shown that
      troponin C has a characteristic single calcium-binding site that is most likely
      to be involved in the regulation of contraction.

PMID- 16106977
TI  - How two-foot molecular motors may walk.

PMID- 16106978
TI  - Molecular basis of calcium regulation of striated muscle contraction.

PMID- 16106979
TI  - Mechanisms of calcium release from the sarcoplasmic reticulum in skeletal muscle.

PMID- 16106980
TI  - From inward spread of activation, active elongation to the effect of organic
      calcium channel blockers in muscle excitation-contraction coupling.

PMID- 16106981
TI  - Cardiac myosin binding protein C: modulator of contractility.

PMID- 16106982
TI  - Human atrial myosin light chain 1 expression attenuates heart failure.
AB  - Most patients with hypertrophic cardiomyopathy and congenital heart diseases
      express the atrial essential myosin light chains (ALC-1) in their ventricles,
      replacing the ventricular essential light chains (VLC-1). VLC-1/ALC-1 isoform
      shift is correlated with increases in cardiac contractile parameters of a
      transgenic rat model overexpressing hALC-1 in the heart (TGR/hALC-1) compared to
      normal WKY rats. To investigate, whether the benefical effects of the hALC-1 on
      cardiac contractility could attenuate contractile failure of the overloaded
      heart, aortocaval shunt operations of 9-10 weeks old WKY and TGR/hALC-1 were
      performed. 5 weeks later, both animals groups were sacrificed for analysis of
      cardiac contraction and transgene expression. Control animals were operated but
      remained normal body and heart weights. The whole heart contractility parameters
      were evaluated using the Langendorff heart preparation. Shunt-operated TGR/hALC-1
      and WKY rats developed comparable levels of cardiac hypertrophy which was
      associated with significant reduction of contractile parameters of the
      Langendorff hearts. However, the decline of cardiac contractility was less
      pronounced in shunt-operated TGR/hALC-1 compared to shunt-operated WKY. In fact,
      developed left ventricular pressure as well as maximal velocity of pressure
      development and relaxation were significantly higher in shunt-operated TGR/hALC-1
      as compared to shunt-operated WKY. Expression of hALC-1 was 17 microg/mg whole
      SDS-protein in control (sham-operated) controls and declined significantly to 14
      microg/mg whole SDS-protein in hypertrophied TGR/hALC-1. These results
      demonstrate that the expression of hALC-1 could have a beneficial effect on the
      overloaded hypertrophied heart.

PMID- 16106983
TI  - Cytoplasmic free concentrations of Ca2+ in skeletal muscle cells.

PMID- 16106984
TI  - Mysterious beauty of beating heart: cardiac mechano-energetico-informatics.

PMID- 16106985
TI  - Is myosin phosphorylation sufficient to regulate smooth muscle contraction?

PMID- 16106986
TI  - Comparative aspects of crossbridge function--skinned fibre studies.

PMID- 16106987
TI  - Dynamic structures of myosin, kinesin and troponin as detected by SDSL-ESR.

PMID- 16106988
TI  - Mutations of transcription factors in human with heart disease for understanding
      the development and mechanisms of congenital cardiovascular heart disease.

PMID- 16106989
TI  - Using biosensors to detect the release of serotonin from taste buds during taste
      stimulation.
AB  - CHO cells transfected with high-affinity 5HT receptors were used to detect and
      identify the release of serotonin from taste buds. Taste cells release 5HT when
      depolarized or when stimulated with bitter, sweet, or sour tastants. Sour- and
      depolarization-evoked release of 5HT from taste buds is triggered by Ca2+ influx
      from the extracellular fluid. In contrast, bitter- and sweet-evoked release of
      5HT is triggered by Ca2+ derived from intracellular stores.

PMID- 16106990
TI  - The basic importance of the physiological approach in clinical medicine: the
      experience in the area of hypertension.
AB  - Since Claude Bernard the physiological approach has dramatically contributed to
      the unprecedented progress that clinical medicine has seen during the second half
      of the 19th and throughout the 20th century. If I go back to about fifty years
      ago, when I started as a medical student and investigator under the guidance of
      Giuseppe Moruzzi and Cesare Bartorelli our understanding of arterial hypertension
      was very small and our therapeutic abilities close to nothing, but progressive
      knowledge of the physiology of the sympathetic nervous system, of the kidney, of
      the renin-angiotensin system, etc, led to a progressive understanding of the
      mechanisms of elevated blood pressure and to the development of an array of
      effective blood pressure lowering drugs, thanks to which hypertension is now a
      controllable disease. The supremacy of the physiological approach to clinical
      medicine has been recently endangered by the rising of two new approaches, whose
      worshippers consider the ultimate ones promising solid conclusions and unforeseen
      progress. These are the large randomized therapeutics trials, that are often
      arrogantly defined as evidence-based medicine (as if they were to provide the
      only real "evidence") and molecular and genetic medicine. Needless to say, both
      are important new tools in medicine, but neither can make the physiological
      method obsolete. The risk of the pretended superiority of the new approaches (and
      the new fashions) is that these claims are unbalancing research activity and its
      financial support, thus weakening the very basis upon which these new
      methodologies are founded and have developed.

PMID- 16106991
TI  - Modulation of sensory input to the spinal cord by presynaptic ionotropic
      glutamate receptors.
AB  - Sensory input from peripheral nerves to the dorsal horn of the spinal cord is
      mediated by a variety of agents released by the central terminals of dorsal root
      ganglion (DRG) neurons. These include, but are not limited to, amino acids,
      especially glutamate, peptides and purines. The unraveling of the mechanisms of
      synaptic transmission by central terminals of DRG neurons has to take into
      account various ways in which the message from the periphery can be modulated at
      the level of the first central synapse. These include postsynaptic and
      presynaptic mechanisms. Homomeric and heteromeric complexes of receptor subunits
      for the different transmitters released by DRG neurons and interneurons,
      clustered at the postsynaptic site of central synapses, can be expressed in
      different combinations and their rate of insertion into the postsynaptic membrane
      is activity-regulated. Inhibitory mechanisms are an important part of central
      modulation, especially via presynaptic inhibition, currently believed to involve
      GABA released by inhibitory intrinsic neurons. Recent work has established the
      occurrence of another way by which sensory input can be modulated, i.e. the
      expression of presynaptic ionotropic and metabotropic receptors in central
      terminals of DRG neurons. Microscopic evidence for the expression, in these
      terminals, of various subunits of ionotropic glutamate receptors documents the
      selective expression of glutamate receptors in functionally different DRG
      afferents. Electrophysiological and pharmacological data suggest that activation
      of presynaptic ionotropic glutamate receptors in central terminals of DRG neurons
      may result in inhibition of release of glutamate by the same terminals. Glutamate
      activating presynaptic receptors may spill over from the same or adjacent
      synapses, or may be released by processes of astroglial cells surrounding
      synaptic terminals. The wide expression of presynaptic ionotropic glutamate
      receptors, especially in superficial laminae of the dorsal horn, where Adelta-
      and C fibers terminate, provides an additional or alternative mechanism, besides
      GABA-mediated presynaptic inhibition, for the modulation of glutamate release by
      these fibers. Since, however, presynaptic ionotropic glutamate receptors are also
      expressed in terminals of GABAergic intrinsic interneurons, a decrease of GABA
      release resulting from activation of these receptors in the same laminae, may
      also play a role in central sensitization and hyperalgesia.

PMID- 16106992
TI  - Synapsins and neuroexocytosis: recent views from functional studies on synapsin
      null mutant mice.

PMID- 16106993
TI  - Heterogeneity of axon terminals expressing VGLUT1 in the cerebral neocortex.
AB  - Using immunocytochemical techniques and confocal microscopy we have studied the
      localization of the vesicular glutamate transporters (VGLUTs) 1 and 2 in the
      mammalian cerebral cortex. The cardinal observations gathered to date can be
      summarized as follows: 1) Many VGLUT1-positive puncta coexpressing synaptophysin
      1 outline pyramidal cell somata and proximal dendrites; of these, a sizeable
      fraction coexpress VGAT, the vesicular transporter for GABA; 2) VGLUT2-positive
      puncta are also present in layers II-III and some of them coexpress VGLUTI. These
      findings suggest that in the cerebral cortex of adult rats axon terminals
      expressing VGLUT1 are heterogeneous.

PMID- 16106994
TI  - Dynamics of secretion.
AB  - In this short review, kinetic aspects of exocytosis are discussed. A special
      emphasis is put on recent data that highlight dynamic differences between
      neurotransmission and other forms of secretion.

PMID- 16106995
TI  - Synaptic plasticity at the cerebellum input stage: mechanisms and functional
      implications.
AB  - The mf-GrC relay provides the case of a synapse at which elementary
      neurotransmission mechanisms are particularly well understood allowing a precise
      investigation of synaptic plasticity. An interesting consequence is that a
      presynaptic mechanism of LTP could be precisely documented on the basis of
      quantal analysis. By being presynaptically expressed, LTP becomes instrumental to
      regulation of short-term synaptic dynamics thereby controlling time-dependent
      transformations of the incoming mossy fiber input. It is unknown to what extent
      these considerations could be generalized, but early observations were provided
      for comparable concepts and mechanisms in neocortical synapses (Tsodyks and
      Markram, 1997). Although several aspects remain to be investigated, mf-GrC LTP
      provides a wide substrate for information storage in the cerebellum. In the rat
      cerebellum, there are 10(11) GrCs and 4 times as many mf-GrC synapses.
      Mathematical models have suggested that mf-GrC LTP improves mutual information
      transfer, and that the combination of synaptic and non-synaptic changes improves
      sparse representation of the mf input (Schweighofer et al., 2000; Philipona et
      al., 2003). Moreover, mf-GrC LTP could play a key role in regulating
      neurotransmission dynamics, implementing adaptability in delay lines early
      envisioned by Breitenberg (1967) and then revisited by Medina and Mauk (2002).
      These observations challenge the simple view of spatial pattern separation
      proposed by Marr (1969). The potential consequences of mf-GrC LTP need to be
      further investigated and confronted with computational models of the cerebellar
      network.

PMID- 16106996
TI  - Advanced tracer techniques to monitor synaptic activity.
AB  - The two approaches presented here bypass postsynaptic receptors as indicators of
      quantal release, and thus they can provide information which is clearly distinct
      from that obtained with standard electrophysiological techniques. Indeed, the
      inherently variable responsiveness of the postsynaptic membrane makes it an
      unreliable indicator of presynaptic activity and this has fueled a lot of
      controversy, particularly in the area of synaptic plasticity. A major advantage
      of these two methods is their ability to detect changes at the single bouton
      level. This offers a lot of advantages including the possibility to study the
      functional role for exo-endocytosis but also plasticity against a background of
      great variability among a large number of synapses. The spatial resolving power
      of FM1-43 and anti-synaptotagmin antibodies may be valuable in future studies of
      spread of LTP between neighboring synapses and in the mapping the pattern of
      neuronal activity in complex networks of neurons.

PMID- 16106997
TI  - Pesticides and the environment.
AB  - In the period 1981-2000, an investigation was conducted on organochlorine
      insecticide (OCI) residues in the environment and their effects on human health.
      The analyses encompassed drinking and surface waters, air, foodstuffs, ready-made
      meals, human serum and human autopsy material. OCI residues were not detected in
      drinking water originating from great distributive systems in Vojvodina (purified
      and conditioned water) but in some sub-artesian wells there were HCH and aldrin
      residues. OCI residues were quantified in surface water of the river Danube which
      is in the required group, except for HCH in 1990/91, when it was in the III-IV
      group. Air was analyzed in Novi Sad, Zrenjanin, Kikinda, Beojin and Apatin. OCI
      residues are regularly tested in Zrenjanin (1996-2000): the most frequently
      detected are: HCH residues (37.83% samples), lindane (21.72% samples), heptachlor
      (17.60% samples) and rarely DTD and aldrin; aldrin (in traces), heptachlor and
      HCH were detected in Novi Sad. Heptachlor, lindane and HCH were also rarely
      determined in Kikinda. OCI have an affinity for fat tissues and their residues
      can be found particularly in foodstuffs originating from animals. They are not
      eliminated by thermal processing and it was established in pre-school
      institutions, student restaurants and homes for the aging; most frequently
      detected was p,p 'DDE isomer, rarely p,p 'DDT as well as HCH and rarely lindane.
      Although use of OCI is forbidden, due to their long persistence in the
      environment, they can be found in human tissues, which was proved by human serum
      analyses. Analyses of human autopsy material indicated presence of DDT metabolite
      -p,p 'DDE as well as lindane in all analyzed samples (brain, liver, fat and
      tumorous tissues).

PMID- 16106998
TI  - [Frequency of occupational injuries and the health status of workers].
AB  - INTRODUCTION: Occupational injuries are the leading cause of morbidity and
      mortality among workers. The aim of this study was to analyze the frequency of
      occupational injuries and health status of workers. MATERIAL AND METHODS: The
      examined group consisted of 3,750 workers with health disorders. The control
      group included 1,800 healthy workers. Both groups were similar in terms of many
      factors that could contribute to the occurrence of occupational injuries. The
      injury rates were calculated in both groups. RESULTS: Workers with psychomotor
      and sensorimotor disorders, neuroses, obstructive sleep apnea, arterial
      hypertension, diabetes mellitus, hearing, vascular and sight impairments have
      been frequently injured compared to workers with other diseases. DISCUSSION: Due
      to the belief that accidents and occupational injuries are preventable, it is an
      imperative to study those factors which are likely to contribute to occurrence of
      accidents. The contributing factors could be the physical and mental state of
      workers. CONCLUSION: Occupational injuries are significantly more common in the
      examined group than in controls.

PMID- 16106999
TI  - [Effects of ginkgo biloba extract on an experimental model of epilepsy].
AB  - INTRODUCTION: The active ingredients of ginkgo biloba extracts were determined by
      biochemical analyses in the last ten years and they are widely used in classical
      medicine. The active substances of ginkgo biloba extract, mostly affect
      muscarinic receptors and adrenergic receptors to a lesser degree. Recently,
      potential effects of ginkgo biloba on NMDA receptors and on epileptogenic
      seizures have been considered. The main goal of this research was to investigate
      effects of ginkgo biloba extracts on the experimantal model of epilepsy. MATERIAL
      AND METHODS: The research was carried out on chinchilla rabbits. GINGIUM solution
      was used with 40 mg in 1 ml of dry extract of ginkgo biloba leaves. The
      epileptogenic area was formed by stimulating hippocampus. Bioelectrical activity
      was registered 60 minutes before the epileptogenic area was formed as well as 90
      minutes later. Ginkgo biloba extract was given via i.m, in a single daily dose of
      1 ml/kg/BW. RESULTS: A statistically significantly higher frequency of paroxysmal
      seizures was established after usage of ginkgo biloba. CONCLUSION: According to
      the results obtained in this research, we can conclude that ginkgo biloba
      extracts have a proconvulsive activity.

PMID- 16107000
TI  - [Cyclic intravenous pamidronate in treatment of osteoporosis].
AB  - OBJECTIVE: To assess the efficacy and tolerability of cyclic intravenous
      pamidronate therapy in women with severe osteoporosis. MATERIAL AND METHODS: Bone
      mineral density (BMD) measurement was performed by dual-energy X-ray
      absorptiometry using LUNAR DPX-L device. Slow intravenous infusion regimens of
      pamidronate (30 mg) every three months were used in treatment of 240 women, in
      addition to supplemental Ca and vitamin D. Bone mineral density was measured from
      lumbar spine 1 year later (120 mg of pamidronate) in 195 women and 2 years later
      (240 mg of pamidronate) in 29 women. The placebo group included 63 women treated
      only with calcium and vitamin D. RESULTS: The average age of 240 women with
      severe osteoporosis was 61.2 +/- 9.5. All were postmenopausal, except for two of
      them. Their mean age at the onset of menopause was 46.2 +/- 5.6. Mean duration of
      menopause was 15.7 +/- 8.1. After 1 year of therapy, bone mineral density
      increased from 0.781 g/cm2 to 0.83 7 g/cm2 (p < 0.001), the mean increase bone
      mass was 7.2% (p < 0.0001). After 2 years, bone mineral density increased to
      0.844 g/cm2, the improvement was 8.1% from baseline (p < 0.001). Bone mineral
      density in the placebo group, after one year, significantly increased (p = 0.046)
      from 0.966 g/cm2 to 1.004 g/cm2, the improvement was 3.9%. However, after two
      years, bone mineral density decreased to 0.973 g/cm2, and compared with baseline
      this change was 0.7% and not significant (p > 0.05). CONCLUSION: Pamidronate
      prevented further decrease of BMD in our patients with severe osteoporosis and
      also increased BMD in these patients. This safe and efficient drug is well
      tolerated.

PMID- 16107001
TI  - [The value of ultrasound in diagnosis of male infertility].
AB  - INTRODUCTION: The number of male patients with clinical presentation of
      infertility, especially secondary infertility after infections, is increasing
      every day. Contemporary urological standards in defining male infertility include
      ultrasound examination. Ultrasound examination of the scrotum using color doppler
      is of great importance. DIAGNOSIS OF MALE INFERTILITY: Testicular atrophy,
      microlithiasis and varicocele are the most common causes of male infertility.
      Microlithiasis and classical testicular microlithiasis are not directly
      associated with infertility. Gray scale sonography is used in evaluation of the
      dilatation of the testicular veins, but color Doppler made a real contribution in
      revealing subclinical varicocele. Transrectal ultrasound is used in a number of
      pathological conditions of prostate, seminal vesicles and ducts. In cases of
      obstructive azoospermia it is important to find out the cause, such as focal
      prostatitis, cysts, ejaculatory ducts obstruction or absence of vas deferens.
      CONCLUSION: Ulltrasound is a noninvasive method easy to perform, which provides
      information without postexamination consequences such as strictures or
      obstructions, which are possible after invasive deferentography. Ultrasound
      guided biopsy, provides a new minimally invasive diagnostic tool in current
      urology.

PMID- 16107002
TI  - [Light induced polymerization of resin composite restorative materials].
AB  - INTRODUCTION: Dimensional stability of polymer-based dental materials is
      compromised by polymerization reaction of the monomer. The conversion into a
      polymer is accompanied by a closer packing of molecules, which leads to volume
      reduction called curing contraction or polymerization shrinkage. Curing
      contraction may break the adhesion between the adhesive system and hard tooth
      tissues forming microgaps which may result in marginal deterioration, recurrent
      caries and pulp injury. POLYMERIZATION SHRINKAGE OF RESIN-BASED RESTORATIVE
      DENTAL MATERIALS: Polymerization of the organic phase (nonomer molecules) of
      resin-based dental materials causes shrinkage. The space occupied by filler
      particles is not associated with polymerization shrinkage. However, high filler
      loading within certain limits, can contribute to a lesser curing contraction.
      POLYMERIZATION SHRINKAGE STRESS AND STRESS REDUCTION POSSIBILITIES:
      Polymerization shrinkage stress of polymer-based dental resins can be controlled
      in various ways. The adhesive bond in tooth-restoration interface guides the
      contraction forces to cavity walls. If leakage occurs, complications like
      secondary caries and pulpal irritation may jeopardize the longevity of a
      restoration. Stress relieve can be obtained by modifications of the monomer and
      photoinitiator, or by specially designed tooth preparation and application of
      bases and liners of low modulus of elasticity. The polymerization contraction can
      be compensated by water absorption due to oral cavity surrounding. The newest
      approach to stress relief is based on modulation of polymerization initiation.
      CONCLUSION: This work deals with polymerization contraction and how to achieve
      leak-proof restoration. Restorative techniques that may reduce the negative
      effect of polymerization shrinkage stress need further research in order to
      confirm up-to-date findings.

PMID- 16107003
TI  - [New insights into transmission of tuberculosis].
AB  - INTRODUCTION: Considering the fact that tuberculosis is a global problem, that
      one third of the world population is infected with tuberculosis and that 8-10
      million of newly recognized cases are detected per year, the need for acquiring
      new knowledge on pathogenesis and transmission of tuberculosis becomes obvious.
      Application of molecular biology methods in clinico-epidemiology practice has
      identified transmission chain of tuberculous bacilli in numerous intrahospital
      outbreaks of tuberculosis. CONDITIONS FAVORING TRANSMITION OF TUBERCULOUS: The
      possibility of transmission primarily depends on the following conditions:
      contagiousness of the patient who is a source of infection, conditions in which
      the exposure takes place, length of exposure, as well as the immune status of the
      exposed individual. RISK FACTORS FOR TRANSSMITION OF TUBERCULOSIS: Unrecognized,
      i.e., untreated tuberculosis represents a major risk factor for environmental
      spread of the bacillus. Therefore, early diagnosis and initiation of adequate
      therapy are priority tasks. High risk of tuberculous bacilli transmission is
      associated with all diagnostic and therapeutic procedures inducing cough, such as
      bronchoscopy, endotracheal intubation, induction of sputum, inhalation therapy as
      well as work in microbiological laboratories dealing with identification of M
      tuberculosis. DISCUSSION: Results of numerous studies indicate that there is
      significant risk for transmission and infection of individuals exposed to the
      source of infection in family settings, work environment or other close contacts.
      The problem of exposure of health workers at their workplaces represents a
      problem in institutions dealing with diagnosis and treatment of tuberculosis.
      CONCLUSION: A more comprehensive insight into significance of the problem and
      application of measures aimed at preventing transmission of tuberculosis should
      lead to practical application of preventive measures proposed by the
      International Union Against Tuberculosis and Lung Disease, in both hospital and
      non-hospital environments.

PMID- 16107004
TI  - [Dilemmas in the surgical treatment of cervical cancer].
AB  - INTRODUCTION: Cervical cancer is the second most common cancer of the female
      genital tract. There are 2200 newly registered cases of cervical cancer each year
      in Serbia, out of which 650 women die. The incidence of invasive, advanced
      cervical cancer has been on decrease, whereas the incidence of "in situ" stage
      carcinoma increases by 2% per year with tendency of increase in the younger age
      groups. HISTORICAL DATA: The first radical abdominal hysterectomy was performed
      by Ernst Wertheim from Wienna in 1898, whereas Schauta performed the first
      vaginal hysterectomy in 1902. It was in 1995 when Daniel Dargent introduced
      radical vaginal trachelectomy combined with laparoscopic lymphadenectomy in order
      to preserve fertility in cases of initial-invasive stages of cervical cancer
      (FIGO I A2, I B1). CHOICE OF SURGICAL PROCEDURE: Before choosing the surgical
      procedure, it is necessary to make a correct preoperative estimation of the stage
      of disease according to FIGO classification. Apart from gynecologic and
      rectovaginal examinations, in some cases it is necessary to perform additional
      examinations such as: cystoscopy, rectoscopy, CT or MRI examination of the
      pelvis, IVU, chest X-ray etc. The decision can be made only by an experienced
      gynecologist-surgeon who is able to solve all complications of treatment by
      himself. CONCLUSION: There are different surgical procedures for cervical cancer:
      abdominal, vaginal and combined. Introduction of laparoscopic lymphadenectomy
      combined with vaginal radical operations, to decrease surgical trauma and
      preserve fertility, has been of great significance.

PMID- 16107005
TI  - Associated congenital anomalies: vestibular fistula, duodenal atresia and
      obstructive refluxing megaureter.
AB  - Congenital gastrointestinal anomalies include spectrum of malformations, simple
      ones as well as complex, which are associated with anomalies of other organs and
      systems of organs. Most infants (50-60%) with imperlbrate anus also have
      genitourinary, cardiovascular, gastrointestinal and vertebral anomalies. This
      case report is of a female newborn with prenatally diagnosed duodenal atresia and
      right hydronephrosis. Clinical investigation revealed an imperforate anus with
      vestibular fistula. A plain abdominal X-ray showed a "double-bubble" sign,
      characteristic for duodenal atresia. Intraluminal membrane was excised and
      sigmoid colostomy was performed in general anesthesia on the first day of life.
      Ultrasound and intravenous pyelography confirmed a hydronephrotic right kidney
      and obstructive megaureter after Pena. In the fifth month of life, the ureter was
      tapered and reimplanted. Six months later, posterior sagittal anorectoplasty was
      performed. In the seventeenth month of life the colostomy was closed This child
      attained normal growth and development, normal bowel control, fecal continence
      without soiling, obstipation and urinary infections.

PMID- 16107006
TI  - [Amnioreduction in treatment of increased amniotic fluid volume].
AB  - INTRODUCTION: Increased amniotic fluid volume may significantly increase the risk
      for preterm delivery. Amniodrainage is a symptomatic treatment by which excess
      amniotic fluid is reduced to provide fetal lung maturation. The aim of this
      stuldy is to estimate the efficacy and safety of this procedure, our results and
      give a literature review. MATERIAL AND METHODS: Sonografic criteria were used
      (AFI >400 ml, or the biggest amniotic fluid pocket >150 mm) to choose patients in
      whom 18G needle was used to allow leaking of excessive amniotic fluid. RESULTS:
      10 patients underwent 26 procedures. The procedures were performed at 28.6 th
      week gestation, on average and 6.25 weeks average gain or 1000 g. We had two sets
      of monochorionic twins with twin-to-twin transfusion syndronme (TTTS), where one
      child survived. One procedure was followed by premature placental abruption, and
      premature delivery in 28th week. The rest of procedures were uneventful.
      CONCLUSION: In our series of 10 women, 26 procedures were performed to prolong
      pregnancies, enable fetal maturation and weight gain. In majority of cases
      amnioreduction was done without complications, so we could repeat the
      intervention and prolong the pregnancy. Survival of one child in two TTTS
      pregnancies should not be regarded unsulccessful in our conditions.

PMID- 16107007
TI  - [Health status of adolescents deprived of parental care].
AB  - INTRODUCTION: Children deprived of parental care are a vulnerahle population with
      complex needs and health problems. The aim of our study was to assess health
      status of this population and compare it with children living in their biological
      families. MATERIAL AND METHODS: Our study included 41 adolescents living in
      foster families (22 boys and 19 girls, mean age 14.66 + 1.39 and 43 adolescents
      living in child foster homes (16 boys and 27 girls, mean age 14.99 +/- 1.3). The
      control group consisted of their classmates living with their biological families
      (45 adolescents, 20 boys and 25 girls, mean age 14.69 +/- 1.43). Health status
      was assessed by analyzing their medical records. Results There were no
      differences in regard to anthropometric characteristics (body weight, body
      height, body mass index) and prevalence of body deformities in studied groups.
      Acute bronchitis was significantly more fequent in children living in foster
      families (41.5%) than in other two groups (16.3%--foster homes: 17.8%--biological
      families). Headaches were significantly more common in groups living in foster
      families (31.70%) and foster homes (25.6%) than in children living with their
      biological families. The same was established for myopia (46.3% foster families:
      32.6%--foster homes; 1 7.8%--biological families). CONCLUSION: Even though there
      were no differences in regard to characteristics which are indicators of general
      health, it is apparent that children deprived of parental care present with
      particularities of health status. Additional researches are necessary in order to
      get insight into the causality of these phenomena.

PMID- 16107008
TI  - [Characteristics of sexual behavior among teenagers in Belgrade].
AB  - INTRODUCTION: The risks associated with teenage sex include pregnancy and a high
      rate of sexually transmitted diseases (STDs). MATERIAL AND METHODS: The study
      compared female teenagers. 32 with STDs and 90 with fungal skin infections who
      were treated in the City Center for Skin and Venereal Diseases in Belgrade from
      January 2000 to June 2001. An anonymous questionnaire was used to collect data
      and an univariate logistic regression analysis was performed RESULTS: Thle mean
      age of participants was 18.2 years. About 40% of respondents reported to have
      their first sexual intercourse at the age of 14-16 years. The majority of cases
      and controls had one or two partners, but a greater percentage of cases had six
      or more partners compared to controls (12.5% vs. 3.3%). Adolescents with STDs
      frequently had sexual intercourse on the first date (p < 0.05), and more
      frequently reported previous STDs in their personal history (p < 0.05).
      Consistent use of condoms was less frequent among cases than among controls, both
      with steady (9.4% vs. 27.8%) and irregular partners (30.0% vs. 70.6%). The
      majority of teenagers (95%) thinks that sexual education at schools should be
      better. DISCUSSION: According to the results obtained, which are in agreement
      with literature data, teenagers should change their behavior, especially with
      respect to condom use both during vaginal and anal sex. Health education at
      schools could probably influence future sexual behavior, and counseling for STDs
      should be offered to all teenagers attending STD clinics. CONCLUSION: The best
      way to avoid unwanted pregnancy and STDs is to delay the first sexual experience,
      reduce the number of sexual partners and increase the protection by condom use.

PMID- 16107009
TI  - [The use of rigid ureteroscope in the treatment of ureteral steinstrasse after
      extra corporeal shockwave lithotripsy of renal calculi--case report].
AB  - INTRODUCTION: Exracorporeal shockwave lithotripsy (ESWL) is the first choice for
      patients with urolithiasis. Increased use of endoscopic techniques provided
      increased use of ureteroscopic lithotripsy in the treatment of stones located in
      distal ureter, as well as ESWL. Rigid ureteroscope is usually used in the
      management of distal ureter stones, while middle and upper ureter stones should
      be treated by flexible ureteroscope or ESWL. At Urology Clinic in Novi Sad,
      ureteroscopy has been used since 1986, and more than 1000 procedures have been
      performed with success rate of over 95% (100% when we were able to reach the
      stone). The aim of this report is to show the destruction of stone along the
      ureter, using a rigid ureteroscope, shortly after the ESWL treatment of kidney
      stones. CASE REPORT: A 46-year-old woman was admitted to the Clinic with
      "steinstrasse" along the ureter, two weeks following ESWL of kidney stones.
      Primarily, she underwent ESWL without J-J stenting, at another urologic
      department. On admission to our Clinic, she complained of pain, nausea, mild
      temperature. An urgent diagnosis was carried out and left sided "steinstrasse"
      with hydronephrosis was confirmed by ultrasound, plain X-ray, laboratory
      findings. Ureteroscopy was performed under spinal anesthesia by rigid
      ureteroscope and the stone was destroyed along the ureter, even the pyelon was
      explored at the end of the procedure. The patient was advised to take a lot of
      fluids with diuretics and 80% of stones were eliminated in the first week after
      the procedure. At the first control, a month later, the patient was stone free.
      CONCLUSION: Rigid ureteroscope is a therapeutic option for distal ureteral
      stones, just as ESWL with comparable and reproducible results. This case confirms
      the fact that in strictly selected cases, and careful work of skilled urologists,
      rigid ureteroscope can be used for successful stone destruction in the middle and
      upper ureter.

PMID- 16107010
TI  - [In situ pedicle graft and coronary-coronary bypass grafting using internal
      thoracic artery in management of multiple lesions of the left anterior descending
      coronary artery].
AB  - INTRODUCTION: Nowadays, coronary-coronary bypass grafting (CCBG) has been applied
      in patients with heavily calcified ascending aorta or due to lack of graft
      material. CASE REPORT: We describe a case in which the patient's large left
      anterior descending (LAD) coronary artery, running well over the cardiac apex,
      presented with proximal and distal stenosis. Although the pedicled left internal
      thoracic artery (ITA) graft is sometimes too short for sequential bypass in cases
      of distal stenosis of the LAD coronary artery, we used a free, short segment of
      the pedicled left ITA for coronary-coronary bypass grafting. The in situ remnant
      of the left pedicled ITA was used to bypass the proximal LAD stenosis. The
      patient's postoperative course was uneventful. Predischarge angiogram (on the 9th
      postoperative day) showed an in situ left ITA graft as well as afree
      coronarycoronary ITA graft. The patient had a regularfollow-up after 3 months,
      and was classified as New York Heart Association (NYHA) class I. DISCUSSION:
      Primarily used in aorto-coronary bypass surgery (termino-terminal interposition
      of the saphenous vein between two parts of a resected coronary artery), CCBG was
      revised latter on, and from hemodynamic point of view the physiologic restoration
      of coronary blood flow has been confirmed CCBG might be an attractive approach
      for bypassing distal lesions of large coronary arteries (combined with arterial
      or venous grafting of targeted arteries, if proximal stenoses are also present).
      The proximal remnant of ITA can be used as an in situ or free graft.

PMID- 16107011
TI  - [New aspects of normolipidemic dyslipoproteinemias].
AB  - INTRODUCTION: Normolipidemic dislipoproteinemias include various disorders of
      different lipoproteins, of their subfractions or some apolipo-proteins, of
      primary or secondary origin, which are widespread among general population and,
      like hyperlipoproteinemias, they are associated with the risk for premature
      atherosclerosis. DECREASED LEVEL OF HDL CHOLESTEROL: It is a primary, familial
      hypoalphalipoproteinemia, which is commonly associated with obesity, diet rich in
      carbohydrates, decreased physical activity and excessive use of coffee and some
      drugs. HYPERAPOBETALIPOPROTEINEMIA: It is characterized by increase of apo B-100
      in LDL particles, most probably as a consequence of increased hepatic synthesis.
      Apolipoprotein E isoforms ApoE4 isoform is associated with elevated LDL
      cholesterol concentration due to rapid IDL to LDL conversion. ELECTROPHORETIC
      DISORDERS: The most important is the latent type IV (pre-beta) or IVb (pre-beta1)
      with decreased VLDL clearance. PROLONGED POSTPRANDIAL LIPEMIA: It is common in
      obesity, NIDDM and coronary heart disease, as an independent risk factor for
      premature atherosclerosis. INCREASED OXIDATIVE MODIFICATION OF THE LDL AND HDL
      PARTICLES: Oxidatively modified LDL may have a key role in the pathogenesis of
      atherosclerosis and oxidative modification of HDL reduces its transport capacity
      and its inhibition of LDL oxidation. INCREASED LEVEL OF LP(A) Lp(a) is an
      independent risk factor for premature atherosclerosis, primarily in young and
      middle-aged men, in persons with elevated global cardiovascular risk factor
      profile, decreased HDL-cholesterol, and hypertension. The risk is smaller in
      persons taking hypocholesterolemic drugs. Also, it is elevated in NIDDM,
      hypothyroidism and kidney disease.

PMID- 16107012
TI  - [The history of audiology].
AB  - INTRODUCTION: The paper presents historical data on development of audiology as a
      medical speciality. It gives the chronological overview of the most significant
      discoveries which have contributed to the progress and constant development of
      the science of hearing. The insights and discoveries encompass the ancient,
      medieval and contemporary medical science. THE TERM "AUDIOLOGY" AND FIRST
      ASSOCIATIONS OF AUDIOLOGISTS: The paper reviews the origin of the term
      "audiology" and the time of its occurrence. The First World Congress of
      Audiologists was held in 1948, and the Conference of Audiologists and
      Phoniatrists of Yugoslavia was established in 1974. HISTORICAL OVERVIEW: The
      ancient scientists and philosophers mentioned in the paper are as follows:
      Democritus, Hippocrates, Empedocles, Plato, Aristotle, and Galenus. Discoveries
      of Vesalius, Fallopio, Eustachio, Duverney, Schelhammer, Catugno and Helmholtz
      marked their epochs and made a great contribution to the development of the
      entire medical science, including audiology. A significant contribution to
      audiology was made by Schwartz in 1920 and Fletcher in 1926, constructors of
      audiometers. Fowler, Weigel and Fletcher promoted an audiogram in 1922. Wever and
      Bray first introduced the cochlear microphonic potentials. The first modern
      audiometer with a flat zero line for all pitches was constructed in 1937. In
      1947, Bekesy constructed the automatic audiometer, and the theory of mobile waves
      was introduced in 1928. Fletcher and Steinberg promoted speech audiometries in
      1929. Mendel and Goldstein described medium latency responses in 1969. The first
      hearing aids worn within the ear appeared in the same year. William House
      pioneered the cochlear implantation in adults in 1969, and the program of infant
      cochlear implants. Jewett described the evoked auditory potentials in 1970. James
      Jerger classified tympanometric curves into three tympanogram types (A, B, C).
      Portmann and Arran introduced transtympanic electrocochleography in 1971. Kemp
      introduced otoacoustic emission in 1978. INSTEAD OF CONCLUSION: finally, the
      paper lists the titles of available dissertations and sub-specialisations in the
      field of audiology defended in Novi Sad and Belgrade.

PMID- 16107013
TI  - [Origin and distribution of brain metastases].
AB  - INTRODUCTION: Malignant neoplasmas account for 20% of overall mortality in
      developed countries, and are the second leading cause of death. According to the
      World Health Organization central nervous system tumors account for 4% of all
      tumors and brain tumors cause 0.2-2.4% of all hospital deaths. By their origin,
      brain tumors are classified into primary and secondary tumors or metastases. The
      aims of this study were to examine the number of metastases, their origin and
      distribution and to compare the prevalence of primary and secondary brain tumors
      during the same period. MATERIAL AND METHODS: A retrospective cohort study
      included 63 adults (40 males and 23 females) with diagnosed brain tumors treated
      during 2001 and 2002 at the Department of Neurology in Novi Sad. Tumors were
      diagnosed by computed tomography and magnetic resonance imaging. RESULTS:
      Secondary tumors were also diagnosed, but without statistical significance (2 =
      0.38; p > 0.05) and metastases were significantly more frequent among men (2 =
      14.22; p < 0.01). Supratentorial metastases were significantly more frequent than
      tumors in other localizations (2 = 23.6; p < 0.01). Multiple metastases were
      estimated in 56% of patients and solitary tumors in 44%, without statistical
      significance (2 = 0.48; p > 0.05). In most cases metastases originated from
      primary lung cancers and tumors of unknown origin. CONCLUSIONS: During the
      studied period more secondary than primary tumors have been diagnosed and more
      multiple than solitary metastases. They were more frequent in men with
      supratentorial distribution as most frequent. Lung cancer proved to be their most
      common source.

PMID- 16107014
TI  - [70 years of the English-Yugoslav Children's Hospital for treatment of
      osteoarticular tuberculosis in Sremska Kamenica].

PMID- 16107015
TI  - [Interleukin-1 signal transduction in interaction between the nervous and immune
      systems].
AB  - Ligand-receptor interactions of the cytokine Interleukin-1 (IL-1) with its target
      cells, and further intercellular signal transduction play the key role in
      manifestation of its biological effects. Peculiarities of IL-1 signaling are
      determined by its unique structure and the composition of its receptors. The
      sphingomyelin pathway of IL-1beta signal transduction is one of the principle
      signal mechanisms providing realization of most, if not all, biological effects
      of cytokine. This signaling pathway is initiated by activation of the membrane
      enzyme neutral sphingomyelinase (nSMase), which catalyses the hydrolysis of
      membrane shingomyelin to the secondary cellular messenger ceramide. It has been
      established that IL-1beta operation in the CNS involves mechanisms mediated by IL
      1 type beta1 receptor and the shingomyeline pathway of cytokine signal
      transduction into the cell. Type 1 IL-1 receptor is necessary for IL-1-induced
      activation of nSMase, the key enzyme of the sphingomyelin cascade. Change in
      nSMase activity in membranes of nerve and immunocompetent cells is the common
      link in the stress reaction of neuroendocrinal and immune system cells. nSMase
      activity seems to be a potential target for testing effects of various
      pharmaceuticals and interventions, while planning strategy of correction of
      immune system dysfunctions and neuro-immune interaction disturbances.

PMID- 16107016
TI  - [Immunological interactions in different forms of coronary heart disease].
AB  - The study included measurement of serum levels of IL-1beta, IL-2, IL-6, IL-8, and
      TNF-alpha, as well as the expression of mRNA IL-1beta, IL-2, IL-6, and TGfb1 in
      the vascular wall of patients with coronary atherosclerosis (angina, myocardial
      infarction). IL-1beta, IL-2, IL-6, IL-8, and TNF-alpha serum levels in patients
      with coronary atherosclerosis were found to significantly higher than those in
      healthy individuals (control group). Detection of IL-1beta, IL-2, IL-6, and TGFb1
      in tissues revealed mRNA of the cytokines under study in radial artery wall. The
      main aortic cytokine was found to be IL-2 (7 samples out of 8); the main
      cytokines in peripheral arteries were IL-1beta and IL-6 (5 samples out of 8). The
      results show that elevation of IL-1beta, IL-2, and IL-8 in patients with coronary
      atherosclerosis demonstrates an immunoinflammatory nature of the disease; the
      detection of dissimilar cytokines in tissue samples reflects not only different
      degree of vessel involvement, but also a phase character of the process.

PMID- 16107017
TI  - [Influence of cultivation conditions on bacterial DNA content and bacterial
      membrane permeability].
AB  - The study included measurement of intracellular and extracellular DNA content and
      evaluation of bacterial membrane condition during plankton growth and in isolated
      communities. This was performed at different stages of bacterial development and
      after heating at the temperature of heat shock system activation. The content of
      intracellular bacterial DNA in the community decreased after 72 hours of
      cultivation growth more prominently than during plankton growth. Change of
      intracellular bacterial DNA content in the community overtook the increase of
      membrane permeability, which may indicate the onset of apoptosis. Heating at 420'
      decreased the permeability of bacterial membranes in the community, but did not
      affect this parameter in the bacteria during plankton growth. Extracellular DNA
      was found in the matrix of the communities after 24 hours of growth. Appearance
      of this DNA after 48-74 hours of cultivation may be associated with apoptotic
      process.

PMID- 16107018
TI  - [Genomic variability of vibrio cholerae El Tor biovariant strains].
AB  - The authors performed comparative analysis of the genomes of 145 clinical and
      environmental isolates of Vibrio cholerae El Tor biovariants using single locus
      and multiplex PCR. The study found that clinical strains isolated from patients
      with cholera formed a genetically homogenous group, where bacterial chromosome
      contained all the tested virulence genes, situated on mobile genetic elements
      that had been acquired by the pathogen at various stages of its evolution.
      Strains isolated from water ecosystems during interepidemic period were
      heterogeneous and formed three groups: a small number of virulent strains; non
      toxigenic vibrio strains that, in the process of reductional variation in their
      new econiche, had only managed to maintain individual virulence genes; non
      pathogenic "water" vibrios, whose chromosome contained only the genes from its
      core part, mobile genetic elements being optionally represented only by the
      persistence island. Molecular typing established genetic relations among V.
      cholerae strains under study.

PMID- 16107019
TI  - [Molecular and genetic characterization of rifampicin- and/or izoniazid-resistent
      strains of M. tuberculosis, isolated in Novosibirsk and Tomsk regions].
AB  - The purpose of the work was to study rifampicin- and izoniazid-resistent strains
      of M. tuberculosis, circulating in Western Siberia, by VNTR and IS6110 typing.
      The authors also studied genetic causes of resistance to these antibiotics and
      undertook a search of new VNTR loci, displaying polymorphism in genomes of
      closely related clonally-disseminated variants of Mycobacterium tuberculosis in W
      Beijing family model analysis.

PMID- 16107020
TI  - [Melanoma cell lines as the basis for antitumor vaccine preparation].
AB  - The aim of the study was to obtain cell lines from tumor samples, and to
      determine phenotypic cell characteristics in order to choose the optimal line for
      vaccine preparation. 15 cell lines with stable growth, varying in cultural growth
      character and cytomorphology, were obtained from samples taken from patients with
      metastatic skin melanoma. Immunofluorescense method was used to determine the
      expression of T- and B-lymphocyte markers, antigens of major histocompatibility
      complex (MHC) class I and II, and CD86 co-stimulating molecule in the cell lines.
      The expression of melanocyte differentiation antigens and cancer/testicular
      antigens was evaluated using immunocytochemical assay. The results allowed the
      authors to distinguish three types of melanoma cell lines according to the
      expression of MHC molecules: MHC-negative; MHC class I positive; MHC classes I
      and II positive.

PMID- 16107021
TI  - [Stress proteins in Alzheimer's disease].
AB  - Alzheimer's disease (AD) progression can be restricted by brain self-defense
      systems for a long time since the onset. Among these an exclusive role is played
      by the system of stress proteins, or heat shock proteins. In AD, stress proteins
      play primarily a neuroprotective role, which is realized through at least 7
      mechanisms: 1) restriction of apoptosis; 2) restriction of NO overproduction; 3)
      disaggregation of extracellular Abeta aggregates; 4) acceleration of Abeta
      elimination from intercellular space; 5) restriction of tau-protein
      hyperphosphorylation; 6) protection of neurons from glutamate toxicity; 7)
      restriction of intracellular Abeta cytotoxicity. Results of studies on protective
      effects of heat shock proteins in AD allow creation of a new trend in the field
      of the treatment, related with developing methods of activation of stress protein
      self-defense system in order to restrict neurodegenerative disorders. The given
      review presents theoretical and experimental prerequisites for such an approach,
      and substantiates its possible efficiency.

PMID- 16107022
TI  - [Cultures of transgenic crown gall from Panax quinquefolium and its total
      ginsenosides content].
AB  - It was clearly demonstrated that the T-DNA of Agrobacterium tumefaciens Ti
      plastid was integrated into the crown gall of Panax quinquefolium L. by the
      experiments of paper electrophoresis. The influences of cultural factors on the
      growth of the crown gall and the ginesnosides accumulation were reported. The
      results showed that MS medium was the best one for the growth of the crown gall.
      The growth and total ginsenoside content reached their maximum at 24th and 28th
      day, respectively.

PMID- 16107023
TI  - [Karyotype analysis of Lonicera japonica and L. maackii].
AB  - OBJECTIVE: To study Lonicera japonica Thunb. and Lonicera maackii (Rupr. ) Maxim.
      chromosome number, karyotype, volume. METHODS: Sections combined with micrograph
      were used to analyse chromosome. RESULTS: Lonicera japonica Thunb. normal diploid
      2n = 18; the relative length was 2n = 18 = 2L +8M, + 6M1 + 2S; karyotpye formula
      was K(2n) = 2X = 18 = 10 sm + 6 m + 2st, which belong to "2A" type; the AS. K%
      was 66.65%. Lonicera maackii (Rupr.) Maxim. normal diploid 2n = 18; the relative
      length was 2n = 18 = 4L + 4M, + 10M1; karyotype formula was K(2n) = 2X = 18 = 10
      sm + 8m, which belong to"2A" type; the AS. K% was 63.28%. CONCLUSION: The
      chromosome number, karyotype, and chromosome volume of Lonicera japonica Thunb.
      and Lonicera maackii (Rupr.) Maxim. were showed clear.

PMID- 16107024
TI  - [Determination of the artificial bezoar powder in the bezoar powder by near
      infrared diffuse reflectance spectrometry].
AB  - OBJECTIVE: To establish a method determinating the artificial bezoar powder in
      the bezoar powder by near-infrared diffuse reflectance spectrometry. METHODS: The
      calibration set and the test set were set up by adding unequal artificial bezoar
      powder to the bezoar powder (content range: 0% - 100%), collecting the NIR
      spectrum of the samples. A mathematical model with partial least squares (PLS)
      was established to predict the test set. RESULTS: The coefficients of
      determination (R2) is 99.42 and the relative mean prediction error (RMSECV) is
      1.93 respectively for the internal cross-validation set obtained. The
      coefficients of determination (R2) is 99. 9 and the relative mean standard error
      prediction (RMSEP) is 0.797, respectively for the test set obtained. The
      correlation coefficient between true and prediction is 0. 9972. CONCLUSION: This
      method is reliable and can be used to control the quality of preparations of
      bezoar powder.

PMID- 16107025
TI  - [Studies on Niuxi with the method of FT-IR spectroscopy and analyze technology
      auxiliary].
AB  - OBJECTIVE: To study the genuine of 32 samples of Niuxi from 14 provinces, and
      compare some samples stored for different time to check the change in the coures
      of store. METHOD: IR spectroscopy and Analyze Technology Auxiliary softeare.
      RESULT: The coefficient correlations had certain difference among these Niuxi
      from different places. They were divided into two parts if r = 0.9840 the
      standerd: trueborn crude drugs (r > 0.9840) and non-trueborn (r < 0.9840). And we
      can know the change in medicinal materials according r. CONCLUSION: The method is
      operated simple and determined fast; the result is reliable; repetitiveness is
      good.

PMID- 16107026
TI  - [Study on three aristololatams from Piper wallichii].
AB  - OBJECTIVE: To study the chemical constituents from Piper wallichii. METHODS:
      Three aristololatams were isolated and purified by chromatography with silica gel
      column and Sephadex LH-20 gel column, and the structures of the compounds were
      identified by spectral analysis. RESULT: Three aristololatams were identified as
      cepharanone B, aristolactam A II and aristololatam A III a. CONCLUSION: Three
      aristololatams were isolated from Piper wallichii for the first time.

PMID- 16107027
TI  - [Isolation and identification of taxane from Taxus chinensis cell cultures].
AB  - OBJECTIVE: To study taxanes of the cell cultures of Taxus chinensis. METHODS: The
      cell cultures were extracted with 95% alcohol, distributed by different solvents,
      isolated via column chromatogaphy on silica gel by eluting with various
      proportions of petroleum ether-ethyl acetate and purified by crystallization with
      ethanol. RESULT: A taxane was isolated from the cell cultures of Taxus chinensis
      and its structure was identified as 2alpha,5alpha, 10beta, 14beta-tetraacetoxy
      taxa-4 (20), 11-diene (Taxuyunnanine C) on the base of spectrum data. CONCLUSION:
      The compound was isolated from the cell cultures of Taxus chinensis for the first
      time.

PMID- 16107028
TI  - [Study on purification of total peony glycoside with D140 macroporous resin].
AB  - OBJECTIVE: To study the extraction process of total peony glycoside from Paeonia
      veitchii Lynvh. METHODS: The extraction process of total peony glycoside with
      D140 macroporous resin adsorbent was selected with different condence of ethanol
      for gradient elution. RESULTS: The optimum condence was 35% ethanol. CONCLUSION:
      The extraction ratio of paeoniflorin was >50%, and the extraction process is
      simple and convenient. The regenaration of resin is easy, this method is
      advisible.

PMID- 16107029
TI  - [Research on the protein C-activating property and influencial factors of protein
      C activator isolated from the venom of Agkistrodon halys].
AB  - OBJECTIVE: To investigate the protein C-activating property and experimental
      conditions that may affect the activities of protein C activator (PCA-SV).
      METHODS: PCA-SV's functional characteristic, possible anticoagulant and amidase
      activities were measured by method of APTT and that of specific chromogenic
      substrate respectively in various experimental conditions. RESULTS: PCA-SV can
      specifically act on protein C. The pH-optimum and temperature-optimum for the
      action of PCA-SV were 6.0 - 7.0 and 37 - 40 degrees C respectively. The
      anticoagulants (heparin, sodium citrate) had no effect on the activities.
      CONCLUSION: PCA-SV is a new protein C-activating reagent that has high potency
      and specificity.

PMID- 16107030
TI  - [Experimental studies of anti-proliferative effects of marinesponge extracts S1 -
      S3 on human lung adenocarcinoma and hepatocarcinoma cells].
AB  - OBJECTIVE: To study the anti-proliferative effects of marinesponge extract-S1 -
      S3 on human lung adenocarcinoma GLC-82, hepatocarcinoma 7402 and gastric
      carcinoma MCG-803 cells in vitro. METHODS: The parameters were got by MTT assay.
      RESULTS: After human lung adenocarcinoma GLC-82, hepatocarcinoma 7402 and gastric
      carcinoma MCG-803 cells were treated by marinesponge extract-S1 - S3 for 48h, the
      growth of lung adenocarcinoma GLC-82 and hepatocarcinoma 7402 cells were
      inhibited significantly by the S3 and the IC50 were 2. 714 microg/ml and 2. 598
      microg/ml respectively; but no significant effect on the gastric carcinoma MCG
      803 cells. The marinesponge extracts S1 and S2 don't show inhibitive effect on
      the proliferation of those three tumor cells. CONCLUSION: Marine-sponge extract
      S3 can inhibit the proliferation of lung adenocarcinoma GLC-82 and
      hepatocarcinoma 7402 cells significantly.

PMID- 16107031
TI  - [Experimental study on the antitumor effects of extracts from roots of Actinidia
      indochinensis in carcinoma cell lines].
AB  - OBJECTIVE: To observe rhe effects of extracts from roots of Actinidia
      indochinensis on the growth inhibition in carcinoma cell lines. METHODS: The
      growth inhibition was analyzed by MTT, cell colony and cell growth curve
      measurement in the stomach carcinoma SGC7901, lymphocytic leukemia L1210,
      lymphoid neoplasm P338D1, tumor of cervix uteri Hela, hepar carcinoma hele 7404,
      melanoma B16 and mouse neuroblastoma x rat glioma hybrid NG108-15 cells lines.
      RESULTS: The growth of all tumor cells were inhibited by extracts from roots of
      Actinidia indochinensis in all cell lines. CONCLUSION: The results showed that
      extracts from roots of Actinidia indochinensis possessed the role of antitumors
      in cell culture.

PMID- 16107032
TI  - [Studies on the extraction and purification of total saponins from Parched Semen
      Ziziphi Spinosae].
AB  - OBJECTIVE: To study the extraction and purification process of the total saponin
      from Parched Semen Ziziphi Spinosae with ethanol and macroporous resin. METHOD:
      The total saponins were extracted with ethanol and purified with macroporous
      resin by orthogonal design, taking content and purity of jujuboside A as
      guideline. RESULTS: The optimum extraction condition was adding 6 times amount of
      80% ethanol and refluxing 3 times, for 30 minutes each time. The purification
      process with macroporous resin HPD-100 was using 0.5% NaOH (150ml), 30% ethanol
      (150ml) to wash out impurity, and 70% ethanol 50 ml to wash out saponin. The
      purity of jujuboside A was up to 17.9% and the eluted ratio 72.8%.

PMID- 16107033
TI  - [Study on extracting oil of radix Angelica sinensis with supercritical CO2].
AB  - OBJECTIVE: To study the extraction of angelica oil by SFE-CO2 (CO2 Supercritical
      Fluid Extraction). METHODS: Investigating the influence of the granule size of
      medical material, extraction temperature, extraction pressure, extraction time,
      releasing and separating condition on the extraction of angelica oil by the
      orthogonal design and other methods. RESULTS: The optimum extraction is as
      follows: the granule size of medical material, 40 mu; extraction temperature, 40
      degrees C; extraction pressure, 25Mpa; extraction time, 2 hours; flow of CO2, 20
      L/h; pressure of separation pot I, 8Mpa; temperature of separation pot I, 50
      degrees C; pressure of separation pot II, 6Mpa; temperature of separation pot II,
      50 degrees C. CONCLUSION: The optimum extraction has high extraction ratio of
      angelica oil. The optimum extraction is reasonable and practicable.

PMID- 16107034
TI  - [Quantitative analysis of Danshensu in Tongmai Oral Solution by HPLC].
AB  - OBJECTIVE: To establish a method by RP-HPLC for determination of content of
      Danshensu (3,4-hydroxybenzyl lacticacid) in Tongmai Oral Solution. METHODS: The
      samples were separated on an ODS column Hypersil C18 (10 microm, 4.6 mm x 200 mm)
      with the mobile phase 0. 5% acetic acid-methanol-dimethyl formamide (99:0.5:0.5).
      The flow rate was 1.2 ml/min, and the detection wavelength was set at 335nm.
      RESULTS: The average recovery of Danshensu was 98.31%, and RSD was 2. 11%.
      CONCLUSION: The method is efficient and accurate with a good repeatability and
      can be used for the quality control of Tongmai Oral Solution.

PMID- 16107035
TI  - [The effect of Bu Yang Huan Wu soup and Tong Mai soup on D-Di, PLC and Pagt of
      traumatic fracture].
AB  - OBJECTIVE: To research the effect of Bu Yang Huan Wu Soup (BYHWS) and Tong Mai
      Soup (TMS) within varieties on D-Di, PLC, Pagt of traumatic fracture. METHOD: 48
      cases are choosen, those are femoral-fractured, age between 18 to 45-year-old and
      in level I - II of ASA. The cases were randomly arranged into 3 groups, 16 cases
      are in each group. Group I is the controlled one, it isn't used any medicine
      which affects cruor. Group II is used BYHWS. Group III is used TMS. Group II and
      III are used medicine for 7 days from the first day in hospital. All patients in
      3 groups are checked D-Di, PLC, Pagt in blood in the first day and the seventh
      day,and their results are compared with the healthy adult's. RESULTS: (1)
      Comparing the D-Di of all 3 groups with the healthy adult's on the second day, P
      <0.01. The D-Di value of group I and group III grows up in 7 days, group I's is
      higher than group III's, but both of them P > 0.01. Value of group II is
      decreased in 7 days, P < 0.05. (2)PLC of all 3 groups is compared with healthy
      adult's, P > 0.01. On the seventh day, PLC of group I and group III increase
      obviously, P < 0.01. Group II's increases to P <0.05. (3) Pagt of 1st day of 3
      groups is compared with the healthy adult's, P <0.05. On the 7th day, Pagt
      increases,in group I P < 0.01, in group II P < 0. 05. in group III P > 0.01.
      CONCLUSION: Pagt rises after traumatic fracture, the blood is in high-agglomerate
      situation. Chinese traditional medicine BYHWS and TMS can decrease the blood
      platelet assemble after trauma a certain extent.

PMID- 16107036
TI  - E. coli O157 and Salmonella spp. in white-tailed deer and livestock.
AB  - Escherichia coli O157 and Salmonella spp. are among the leading causes of food
      borne illness in the United Sates and bacteria have been isolated from numerous
      ruminant animal sources. The objective of this study was to assess the incidence
      of E. coli O157 and Salmonella spp. in white-tailed deer (Odocoileus virginianus)
      and livestock simultaneously grazing the same rangeland. Escherichia coli O157
      was found in 1.25% of cattle, 1.22% of sheep, and 5.00% of water all from samples
      taken in September; however, no E. coli O157 was found in other sampled months or
      any species. Salmonella spp. were found in the highest quantities in deer and
      sheep, 7.69% and 7.32%, respectively. Salmonella spp. were also found in sampled
      water troughs, goats, and cattle (5.00%, 3.70%, and 1.25%, respectively). Further
      research examining pathogen distribution is needed to determine if white-tailed
      deer are a natural reservoir for these bacteria.

PMID- 16107037
TI  - Physiological Achilles' heels of enteropathogenic bacteria in livestock.
AB  - An elaborate feeding regimen of animals, which takes advantage of the Achilles'
      heels of enteropathogenic bacteria, can possibly enable prophylaxis in the
      intestinal tract, attenuate actual disease symptoms, accelerate recovery from a
      bacterial gastroenteritis or ensure food safety. There is a wide spectrum of
      conceivable weak spots in bacteria. Some pathogenic bacteria cannot use certain
      compounds, or use them less efficient than beneficial bacteria. By addition of
      such substances to animal feed, non-pathogenic bacteria can grow better than
      pathogens and competitively exclude the latter ones. Other compounds even have an
      inhibitory effect on pathogens. Calcium phosphate for example protects against
      Salmonella, Zn2+ has a prophylactic effect against Brachyspira, and Fe2+ has an
      inhibiting effect on the enterotoxin synthesis of Yersinia enterocolitica.
      Besides, there are antimicrobial substances as plant extracts, essential oils,
      organic acids and other compounds, which inhibit pathogens more than other
      bacteria. A simultaneous application of several anti-pathogen agents suggest an
      enhanced effect. Some countermeasures aim at a distinct group of bacteria, while
      others are more universal. General strategies to repel different pathogenic
      bacteria are the supply of health-stimulating milk components, antagonistic
      bacteria for competitive exclusion, and mucus-related attractants for misguidance
      of adhering and invasive bacteria. This paper gives an overview of Achilles'
      heels of enteropathogenic bacteria that can be exploited to develop strategies
      for keeping control over these pathogens in the gastrointestinal tract of
      livestock.

PMID- 16107038
TI  - Selected topics in probiotics and prebiotics: meeting report for the 2004
      international scientific association for probiotics and prebiotics.
AB  - On August 29-31, 2004, 84 academic and industry scientists from 16 countries
      gathered in Copper Mountain, Colorado USA to discuss certain issues at the
      forefront of the science of probiotics and prebiotics. The format for this
      invitation only meeting included six featured lectures: engineering human vaginal
      lactobacilli to express HIV-inhibitory molecules (Peter Lee, Stanford
      University), programming the gut for health (Thaddeus Stappenbeck, Washington
      University School of Medicine), immune modulation by intestinal helminthes (Joel
      Weinstock, University of Iowa Hospitals and Clinics), hygiene as a cause of
      autoimmune disorders (G. A. Rook, University College London), prebiotics and bone
      health (Connie Weaver, Purdue University) and prebiotics and colorectal cancer
      risk (Ian Rowland, Northern Ireland Centre for Food and Health). In addition, all
      participants were included in one of eight discussion groups on the topics of
      engineered probiotics, host-commensal bacteria communication, 'omics'
      technologies, hygiene and immune regulation, biomarkers for healthy people,
      prebiotic and probiotic applications to companion animals, development of a
      probiotic dossier, and physiological relevance of prebiotic activity. Brief
      conclusions from these discussion groups are summarized in this paper.

PMID- 16107039
TI  - Human flora-associated (HFA) animals as a model for studying the role of
      intestinal flora in human health and disease.
AB  - Although the intestinal flora in animals plays an important role in health and
      disease, there is little direct information regarding the role of the human
      intestinal flora. By inoculating germfree animals with human faeces, the major
      components of the human flora can be transferred into the ex-germfree animals,
      i.e. human flora-associated (HFA) animals. HFA animals therefore provide a stable
      model for studying the ecosystem and metabolism of the human intestinal flora.
      Results with HFA animals suggest the role of the human intestinal flora is
      somewhat different from the role of the animal flora in conventional experimental
      animals. Studies using HFA animals, therefore, will provide much needed
      information on the precise role of the intestinal flora in relation to humans.
      HFA animals also can be used as models to investigate the interactions between
      the human intestinal flora, host factors, dietary manipulations, and
      therapeutics, such as probiotics, prebiotics, and antibiotics.

PMID- 16107040
TI  - Cell death and human intestinal protozoa: a brief overview.
AB  - Protozoan programmed cell death or apoptosis is an important factor in the
      survival of the parasite and its pathogenicity. The most amazing aspect of
      protozoan cell death is in its molecular architecture. To date, protozoa lack
      most of the components of the highly complex cell death machinery studied in
      multicellular organisms. Hence the unique apoptotic machinery in protozoa can be
      exploited for the development of therapeutic drugs and diagnostic markers. This
      review focuses on human intestinal protozoa undergoing cell death and inducing or
      inhibiting host cell apoptosis. The first part of this review focuses on
      intestinal protozoa that undergo PCD under various stress conditions. The second
      part focuses on protozoa that induce or inhibit PCD in their host cell. Although
      these intestinal parasites differ in their mechanism of infection and
      intracellular localization, they may activate conserved cell death pathways
      within themselves and in the host cell. Understanding conserved cell death
      pathways in the intestinal protozoa and their host-parasite PCD relationship may
      lead to drug targets which can be used for a broad range of parasitic diseases.

PMID- 16107041
TI  - Predictors of treatment utilization in world trade center attack disaster
      workers: role of race/ethnicity and symptom severity.
AB  - This study examined treatment utilization in disaster workers deployed to the
      World Trade Center (WTC) during or after the terrorist attacks of September 11,
      2001. Among 174 workers who accepted psychotherapy referrals following
      psychiatric screening for WTC-related symptoms, 74 (42.5%) attended at least one
      session, while 100 (57.5%) chose not to attend at all. The study assessed whether
      treatment utilization was associated with sociodemographic background, trauma
      history, psychiatric history, WTC attack exposure, diagnoses, or symptom
      severity. Analyses indicated that, of study variables, race/ethnicity and
      clinician-rated Post Traumatic Stress Disorder (PTSD) symptom severity
      distinguished workers who utilized treatment from those who did not. Implications
      for outreach and referral are discussed.

PMID- 16107042
TI  - Police officer suicide: causes, prevention, and practical intervention
      strategies.
AB  - More police officers die by their own hand than are killed in the line of duty.
      This article outlines the facts and statistics about police officer suicide and
      discusses the range of possible contributory factors to officer burnout,
      depression, and suicide. It then describes the range of prevention strategies
      that police agencies can employ to minimize this tragedy, including
      identification of risk factors, sensitivity to overt and subtle cues of officer
      distress, and proper utilization of counseling and referral services. Next, the
      article offers practical guidelines for dealing with officers in states of
      impending or acute suicidal crises. Finally, the importance of suicide prevention
      and intervention in the context of comprehensive mental health services for all
      public safety workers is highlighted.

PMID- 16107043
TI  - Attachment and compassion fatigue among American and Israeli mental health
      clinicians working with traumatized victims of terrorism.
AB  - This study compared the construct of compassion fatigue with the role of
      attachment as a potential mediator among mental health clinicians working with
      victims of terrorism in the New York metropolitan region of the United States and
      Israel. Differences between clinicians practicing within Israel (n = 31) and New
      York (n = 35), in terms of their symptoms of compassion fatigue, compassion
      satisfaction, and "burnout," were not significant, as measured by multivariate
      analyses of variance. Based upon nonsignificant differences, mediational
      statistical tests could not be run; thus, mediation did not hold. The data failed
      to support a significant difference between compassion fatigue and attachment
      avoidance or anxiety. However, data collection resulted in attenuated scores for
      compassion fatigue and compassion satisfaction within both study groups of
      clinicians and moderate to average scores for burnout. Israeli clinicians had
      significantly more avoidant attachment dimensions than their New York cohorts.
      The strongest predictors of compassion satisfaction were (a) low attachment
      anxiety and (b) sufficient clinical experience related to treating victims of
      trauma. The strongest predictors of burnout were (a) minimal clinical experience,
      (b) minimal experience working with trauma victims, and (c) greater avoidant
      attachment dimensions.

PMID- 16107044
TI  - Family support and victim identification in mass casualty terrorist attacks: an
      integrative approach.
AB  - Terrorist bombing attacks in Israel between 2000 and 2004 caused mass casualties.
      After each attack in the north of Israel, Rambam Medical Center, the largest
      hospital in the region, absorbs the majority of injured, especially the more
      severely injured and unidentified victims. Immediately with the media reports of
      a terrorist attack, tens of relatives come to the hospital, looking for missing
      family members. This paper describes an assistance unit for families of
      unidentified victims. It is staffed by the hospital's social work department, and
      its tasks are to identify the unidentified victims, help relatives find and be
      united with them, and assist other relatives in the identification of bodies of
      deceased family members. The process involves gathering information from
      relatives and cross-checking it with data and pictures from the hospitals'
      emergency and operating rooms; and providing crisis intervention and
      psychological first aid to victims' relatives. The family assistance unit works
      with several other professional units in the hospital and in the community, and
      always adjusts its operations to the features of each event. Clearer guidelines
      for dynamic training of social workers and research-based interventions to
      prevent compassion fatigue among the workers must be further developed.

PMID- 16107045
TI  - Enhancing the crisis management briefing.
AB  - The Crisis Management Briefing (CMB) is a powerful and versatile crisis
      intervention tool, effective within a wide variety of populations, settings, and
      critical incidents. Initially proposed by Everly (2000), the CMB uniquely fills
      the factual information void following a critical incident. Additionally, a CMB
      provides essential information on effective coping strategies and available
      helping resources, tailored to the specific incident(s). The authors expand on
      the original CMB construct using their combined field experience, offering
      recommendations on team composition, strategic planning factors, using CISDs vs.
      CMBs, and specific enhancements for the four phases. They conclude with examples
      of specific interventions across a variety of events to illustrate their
      recommendations.

PMID- 16107046
TI  - [Analysis of risk factors for deficits in the quality of life in allergic
      rhinitis patients].
AB  - To assess the possible negative aspects in the quality of life (QOL) of patients
      with allergic rhinitis based on the factors such as the symptoms and examination
      of the nasal cavity, we examined QOL deficits using the Japanese Rhino
      conjunctivitis Quality of Life Questionnaire (JRQLQ No1). Thirteen hundred
      seventy eight allergic rhinitis patients who visited clinics or hospitals between
      April and July 2003 were assessed for clinical symptoms, had the examination of
      their nasal cavity graded and answered QOL questionnaires. Gender, period of the
      disease, antigen, clinical symptoms and the results of the nasal cavity
      examination were evaluated and analyzed to reveal risk factors associated with
      negative QOL factors. These negative QOL factors tended to be more severe in
      women than in men, and more severe in pollen allergy than in house dust mite
      allergy. There was no association of the period of the disease with negative QOL
      factors. It was revealed that nasal discharge was the strongest risk factor for
      problems in usual daily activities, outdoor activities and social functioning in
      six QOL domains, and nasal congestion was the major factor associated with sleep
      problems, general physical problems and emotional function. Nasal congestion was
      also the strongest risk factor in the total score of the QOL questionnaire and
      the overall face scale of the patients. In the nasal cavity examination, the
      amount of aqueous secretion was the strongest risk factor for all items
      associated with negative QOL factors. According to the risk factors we
      identified, we can treat allergic rhinitis patients taking their QOL into
      consideration.

PMID- 16107047
TI  - [Endoscopic resection of benign and malignant tumors in the nasal cavity and
      paranasal sinus].
AB  - Endoscopic resection of nasal and paranasal sinus tumors is more aesthetic and
      less invasive than conventional resection, such as Luc's operation and lateral
      rhinotomy. We clarified the effect of radical endoscopic tumor excision and the
      control of local bleeding hazardous in endoscopic surgery. Subjects were patients
      with benign lesions in the nasal cavity, medial wall of the maxillary sinus,
      ethmoid sinus, and/or sphenoid sinus without concurrent malignant lesions.
      Although patients selection for malignant tumor excision was based on (1)
      possible en bloc resection, (2) low-grade malignant tumors, and (3) tumors in the
      nasal cavity and adjoining paranasal sinus, the final decision was made
      individual. Subjects were 23 patients with benign tumor (10 inverted papilloma, 9
      hemangioma, 2 juvenile angiofibroma, and 2 other tumors) and 4 with malignant
      tumor (olfactory neuroblastoma, acinic cell carcinoma, squamous cell carcinoma,
      and chondroid chordoma) in the nasal and paranasal sinus. The tumor was resected
      en bloc except for patients with inverted papilloma (2 cases) and chondroid
      chordoma. Recurrence in benign tumors was zero during a mean observation of 21
      months. One with chondroid chordoma, however, suffered a recurrent lesion 7
      months after the initial operation. The lesion was successfully salvaged by a
      similar endoscopic procedure and subsequently treated with electron beam
      irradiation. Preoperative arterial embolization, laser coagulation, and ligation
      of the sphenopalatine artery were very useful in reducing blood loss during
      surgery and maintaining a clear endoscopic view. In intraoperative bleeding
      volume, less than 100 ml of bleeding occurred during surgery in 23 of 27
      patients. The endoscopic excision of benign lesions in the nasal and paranasal
      sinus is thus as effective as conventional radical surgery. Endoscopic removal of
      malignant lesions remains controversial because of the small number of patients
      and short postoperative observation.

PMID- 16107048
TI  - [Association between laryngeal findings and vocal qualities in muscle tension
      dysphonia with supraglottic contraction].
AB  - Muscle tension dysphonia (MTD) is a voice disorder associated with abnormal
      laryngeal posture or glottic configuration induced by excessive contraction of
      the laryngeal muscles, and supraglottic contraction is one of the characteristic
      findings in MTD. In recent study we investigated the changes in laryngeal
      findings and voice quality and the association between them in the course of
      voice therapy for MTD with supraglottic contraction. The effects of voice therapy
      on the laryngeal and the vocal findings were assessed by two rating methods: the
      MTD score and the conventional GRBAS scores and both scores were gradually
      improved. Of the two components of supraglottic contraction, false vocal cord
      compression was more curable than anterior-posterior compression at the
      aryepiglottic level. Little correlation was found between the scores at the first
      examination, but significant associations (p < 0.05) were found between the
      differences of MTD score and G/R/S scores but not B/A scores before and after the
      series of voice therapy. These results suggest that supraglottic contraction is a
      crucial factor worsening voice quality and that MTD score is useful to assess the
      efficacy of voice therapy for MTD.

PMID- 16107049
TI  - [Problems in the evaluation of hearing of infants].
AB  - Infant hearing loss should be identified early to prevent delays in the
      development of speech and language. However, evaluation of hearing of infants is
      not so easy, because training is required to estimate auidiometric thresholds
      from behavioral testing such as conditioned orientation response audiometry
      (COR). Most ENT physicians who are not capable of behavioral testing tend to
      evaluate hearing of infants only from testing auditory brainstem response (ABR).
      Information about the infant's auditory response to the environmental sounds
      could be obtained easily and might be a substitute for a behavioral testing. We
      administered a questionnaire to the parents to obtain accurate information about
      the infant's auditory response. Tanaka-Shindo's developmental battery test of
      auditory function is an established questionnaire with various questions about
      auditory response and development of speech according to the age of infants from
      0-15 month. We administered Tanaka-Shindo's questionnaire to the parents of
      infants before 8 months, and administered the following questionnaire to the
      parents of infants over 8 months. (1) If you call out the child's name from
      behind, does the child turn his/her head? (2) Does the child turn his/her head to
      any sounds on television, to any small sounds (for example: listened when someone
      opens the door or opens wrapping paper), or to beeping sounds from electric
      devices? To investigate the clinical usefulness of the questionnaire to estimate
      hearing in infants, 79 children (under 4 y.o.) evaluated their hearing at the
      Tottori University Hospital were studied. Forty-three out of 45 (95.6%) who had
      normal hearing had yes in the questionnaire, but the 18 who had moderate to
      severe (60 dB) hearing loss did not have yes in the questionnaire. For the
      mentally retarded 33 children, 27 out of 29 (93%) who had normal hearing had yes
      in the questionnaire, but the 4 who had moderate to severe hearing loss did not
      have yes in the questionnaire. Questionnaire about the infant's auditory response
      is useful to differentiate between normal hearing and moderate to severe hearing
      loss. We recommend our questionnaire as screening procedure to most ENT
      physicians to identify hearing loss in infants. It is important refer patients
      not evaluated as normal to an ENT physician who is capable of diagnosing the
      hearing of infants by behavioral testing.

PMID- 16107050
TI  - [Potentiation of the effects of radiotherapy combined with Th1 cell therapy for
      the treatment of lung cancer in mice].

PMID- 16107051
TI  - [Preparation of SYT gene knockout mice and their analysis].

PMID- 16107052
TI  - [Establishment of SCID mouse models for transplantation of cancerous human
      urinary epithelial tissue and their usefulness in cancer research].

PMID- 16107053
TI  - [Cytokine production control and tumor rejection effect of NKT cells activated by
      dendritic cells].

PMID- 16107054
TI  - [Basic study on establishing a new diagnostic method for superior mesenteric
      artery syndrome by using MDCT].

PMID- 16107055
TI  - [Analysis of the host factors necessary for HIV-1 replication--an evaluation
      through experimental fusion of HIV-1-infected rat cells and human cells].

PMID- 16107056
TI  - [Ultrastructural changes and proliferative capacity of Helicobacter pylori in the
      natural water deep in the ground].

PMID- 16107057
TI  - [Evaluation of the urinary phosphorus content in the early stage following
      remission induction as a prognostic factor in acute lymphocytic leukemia in
      children].

PMID- 16107058
TI  - [Effects of local administration of cyclophosphamide on mandibular condyle growth
      in growing rats].
AB  - The purpose of this study was to identify the effects of the local administration
      of cyclophosphamide (CP) on mandibular condyle growth in growing rats. Sixty
      three 4-week old male Sprague Dawley rats were used in this study. In the
      experimental group, CP (50 mg/ml) 0.02 ml was injected into both articular
      capsules of the condyle, while the control group was injected with physiological
      saline (Experiment I). Histological observation: The animals were sacrificed
      either at 3, 5, or 7 days after injection of CP or physiological saline. The
      condyles were extracted and the sections were prepared for histological and
      histomorphometric observations. The number of BrdU positive cells, the number of
      osteoclasts, the thickness of the cartilage layer and the amount of endochondral
      bone growth in the condyle were measured (Experiment II). Morphological
      observation : 4-week-old male Sprague-Dawley rats were grouped into control
      group, CP (25 mg/ml) treated group, and CP (50 mg/ml) treated group. These
      injections were performed one time at 7-day intervals, and then all rats were
      killed on the 7 th day after the last injection. The effects of CP local
      administration on the mandible were investigated morphologically using
      cephalometric analysis. In experiment I, there was a significant decrease in the
      BrdU positive cells, the thickness of the cartilage layer, and the amount of
      endochondral bone growth in the experimental group. In experiment II, the condyle
      of the CP (50 mg/ml) treated group was significantly shorter than that of the
      control group. These results demonstrate that local administration of CP into
      growing condyle inhibited mandibular condyle growth.

PMID- 16107059
TI  - [Immunological studies on the peripheral blood mononuclear cells in metal allergy
      patients].
AB  - Recently, the number of patients with dental metal allergy has risen
      significantly. The aim of this study was to evaluate the clinical availability of
      the lymphocyte stimulation test (LST) using metal reagents as a method for
      diagnosing metal allergy. In vitro, peripheral blood mononuclear cells (PBMC)
      from 18 patients with metal allergy and five healthy volunteers were examined by
      LST using 12 metal reagents (HAuCl4, PdCl2, NiSO4, CoCl2, CuSO4, SnCl4, K2Cr2O7,
      MoCl5, H2PtCl6, IrCl4, AgBr, FeCl3). To define metal allergy, a patch test (PT)
      was performed with metal reagents, and then the components of dental alloys in
      their mouth were analyzed. The expressions of CD 4, CD 8, CD 25, and CLA of metal
      specific T cells were determined by flow cytometric analysis (FACS). PBMC from
      patients with positive PT showed LST positive for nickel sulfate (Ni), gold
      chloride (Au), palladium chloride (Pd) and cobalt chloride (Co). The results of
      LST in other metals indicated negative in spite of the positive result by PT.
      FACS results indicated the increase of CD 4 + T/CD 8 + alpha 4 + T cells, CD 4 +
      T/CD 8 + CLA+ T cells by stimulation with metal reagent. Thus, metal-specific T
      cells were stimulated in PT positive patients, so LST could be a more specific
      test for diagnosing dental metal allergy.

PMID- 16107060
TI  - [Changes of general and oral health status of elderly patients receiving home
      visit dental services].
AB  - This study investigated the changes of general and oral health status of elderly
      patients who received home-visit dental services. The subjects were 51 patients
      (male: 19, female: 32, age: 83.0+/-9.1). The results of initial and re
      examination (5.4 months later) by questionnaire survey, oral status and oral
      microbes were compared. The following results were obtained. 1. More than half of
      the subjects were bedridden and about 70% were affected by dementia. Three
      quarters needed special care for daily activities. 2. The general health
      condition of the subjects became worse after 5.4 months. Moreover, 11 subjects
      died within 6 months after re-examination. However, oral health status, such as
      status of oral hygiene (p < 0.01), inflammation of gingiva (p < 0.01), tongue
      coating (p < 0.05) and oral malodor (p < 0.01) improved significantly. 3. There
      was a significant difference in the rate of people with dysphagic problems
      between the living and dead groups (p < 0.05). 4. The initial general and oral
      health status of the people with dysphagic problems was significantly worse than
      that of those without it. After receiving home-visit dental services, general
      condition became worse. However oral status, such as status of oral hygiene,
      inflammation of gingiva, oral malodor, and lactobacillus count significantly
      improved in both groups. These results suggest that dysphagic problems of elderly
      patients may affect their general health condition and might increase the risk of
      death. It is recommended to judge dysphagic problems accurately when performing
      certification of need for long-term care and to provide professional oral care
      periodically for the dependent elderly needing care.

PMID- 16107061
TI  - [Lidocaine transportation through a cellophane membrane by wide range AC
      frequencies].
AB  - This study examined whether lidocaine molecules can be transported through an
      artificial membrane by the application of AC. A cellophane membrane was placed
      between donor and receptor compartments. The donor compartment was filled with
      lidocaine hydrochloride (40 and 60 mmol/l) and the receptor compartment with pure
      water. A sine wave at 5 voltage levels and 5 frequencies was applied between the
      parallel plate electrodes. The impedance of the solution in the receptor
      compartment was measured to determine the concentration of the lidocaine. The
      transportation efficiency in the condition of high concentration was markedly
      enhanced with the application of 15 and 20 V at every frequency. Although no
      frequency dependence was observed in the 500 Hz to 100 kHz range, the
      transportation efficiency was markedly enhanced at 1 MHz. It is considered that
      lidocaine ions are transported by vibration or rotation energy induced by AC. The
      formation of electrode polarization is decreased in the high-frequency range
      resulting in attenuation of the voltage drop in the solution and increase of the
      transportation efficiency with the passage of AC.

PMID- 16107062
TI  - Emerging infections and children: influenza and acute necrotizing encephalopathy.

PMID- 16107063
TI  - Chickenpox party or varicella vaccine?
AB  - The most compelling rationale for introducing universal vaccination against
      varicella was the predicted benefits to healthy children. Current evidence from
      the US experience indicates that these benefits are being realized. As is true
      for any new vaccine, implementation of such a program necessitates disease
      surveillance and modifications of the vaccine regimen as needed. In the case of
      VZV, the epidemiology of herpes zoster must be tracked as well as varicella
      disease trends. The prevention of herpes zoster may be another use of live
      attenuated or inactivated varicella vaccines.

PMID- 16107064
TI  - The ABC of Epstein-Barr virus infections.
AB  - The EBV has evolved mechanisms that allow it to take advantages of different
      aspects of the human immune system, resulting in evasion of the defense
      mechanisms of the host. The virus is capable of resting calmly in a "sea of
      tranquility". The virus has the unique ability among herpesviruses to transform
      infected B lymphocytes, thereby creating the potential for uncontrolled
      lymphoproliferation. Such lymphoproliferation occurs when the immune system is
      deregulated as a result of inborn defects or acquired defects (e.g., XLP syndrome
      and organ transplantation, respectively). Otherwise, EBV is kept in check by the
      surveillance activity of cytotoxic T lymphocytes and NK cells.

PMID- 16107065
TI  - The immune response to viral lower respiratory tract infection.

PMID- 16107066
TI  - Chronic granulomatous disease: from genetic defect to clinical presentation.

PMID- 16107067
TI  - Novel primary immunodeficiencies.

PMID- 16107068
TI  - Periodic fever.

PMID- 16107069
TI  - BCG vaccine.

PMID- 16107070
TI  - Rabies on the doorstep.

PMID- 16107071
TI  - Prevention of typhoid fever.

PMID- 16107072
TI  - Dexamethasone in the treatment of pediatric bacterial meningitis in developing
      countries: is it beneficial?

PMID- 16107073
TI  - Should dexamethasone be part of routine therapy of bacterial meningitis in
      industrialised countries?
AB  - Two issues are clear from the data available regarding the current place of
      dexamethasone in routine management of suspected bacterial meningitis in
      industrialised countries. First, there is now good evidence of benefit from
      adjunctive dexamethasone therapy which is not confined to Hib meningitis, but in
      the case of pneumococcal meningitis probably requires that dexamethasone is given
      with or before, rather than after, parenteral antibiotics. In meningococcal
      meningitis, statistically significant benefit has not been demonstrated for any
      outcome, even in meta-analyses, but the point estimate is in the direction of
      benefit and failure to demonstrate an effect is more likely to be due to limited
      power from low event rates rather than no benefit; certainly there is no evidence
      of a detrimental effect. Most culture-negative cases of presumptive bacterial
      meningitis outside the neonatal period are likely to be due to one of the above 3
      organisms. In the neonatal period or in some settings in developing countries,
      the spectrum of organisms is very different and extrapolation of these findings
      cannot be assumed. Second, the suggestion that dexamethasone is not applicable to
      certain subgroups in industrialised countries (such as cases not treated with
      cefuroxime, or some other sub-optimal therapy, or cases treated with vancomycin)
      (5) or that benefit only applies to hearing loss or Hib cases, either do not
      stand up to scrutiny or are not answerable from available data. What does this
      mean for clinical practice? The results of randomised controlled trials may not
      readily translate to clinical practice, particularly with respect to early
      commencement of steroids. The Sydney data show that in a representative developed
      country population with good access to services, after controlling for other
      prognostic variables, early corticosteroid therapy is associated with improved
      outcome. These data also show that deferred lumbar puncture is frequent and so
      criteria requiring presumptive identification of an organism are not practical to
      guide dexamethasone use, indeed those patients in whom lumbar puncture is
      deferred are more likely to have severe disease. This experience is an important
      addition to the findings from clinical trials of dexamethasone in pneumococcal
      meningitis in industrialised countries (5,6) as it demonstrates that adjunctive
      steroid therapy is beneficial in a 'real world' situation. In addition, the
      prospect of clinical trials in children, already limited by small case numbers,
      will be further reduced when the use of the conjugate pneumococcal vaccines is
      widespread. In Canada, a trend to decreasing use of corticosteroids was noted
      between 1991 and 1999, probably reflecting conflicting evidence. (16). Unless
      clear protocols are in place, the commencement of steroids before or with
      antibiotics will be difficult to implement in emergency situations, as
      illustrated by the data from Sydney.

PMID- 16107074
TI  - How to interpret a CSF--the art and the science.

PMID- 16107075
TI  - Reverse vaccinology and vaccines for serogroup B Neisseria meningitidis.
AB  - Whole genome sequence data are increasingly available for a wide range of human
      pathogens. The use of bioinformatic tools allows the comprehensive in silico
      screening of genome data for surface-expressed proteins, in order to identify
      candidate vaccine antigens. In vitro confirmation of surface location and the use
      of animal models to test immunogenicity further refine the list of proteins
      likely to be of use as vaccine antigens. This process, first applied to serogroup
      B Neisseria meningitidis, has been termed as reverse vaccinology. Reverse
      vaccinology offers the ability to undertake a rapid and comprehensive assessment
      of a micro-organism's surface protein repertoire, and has advantages over
      conventional approaches to identifying candidate antigens. Despite the advantages
      of the approach, development in conventional areas of vaccinology remains
      important to support the process of producing vaccines from genome-derived
      antigens.

PMID- 16107076
TI  - Trading for a high.

PMID- 16107077
TI  - Life after death.

PMID- 16107079
TI  - When gambling becomes obsessive.

PMID- 16107078
TI  - Crossing the moral threshold.

PMID- 16107080
TI  - Mmm, chocolate bars.

PMID- 16107081
TI  - Bill's crusade.

PMID- 16107082
TI  - [Extra-hippocampal temporal lesions inducing symptomatic drug-resistant
      epilepsies. Which surgical procedure?].
AB  - In partial symptomatic epilepsy due to discrete brain lesion, total removal of
      the epileptogenic lesion generally yields major reduction of seizures, achieved
      in 85% of the patients. However, prognosis is worse in patients with symptomatic
      temporal lobe epilepsy. Implication of the temporo-mesial structures in the
      seizures genesis is generally considered. Careful electroclinical and
      radiological analysis can provide useful but insufficient information. In order
      to evaluate the criteria we used to guide our surgical strategy, we analyzed
      retrospectively a series of 47 patients with drug-resistant symptomatic extra
      hipocampic temporal epilepsy surgically treated either by isolated lesionectomy
      (group 1, n=17) or by resection of temporo-mesial structures and associated
      lesionectomy (group 2, n=30). Patients with extrahippocampal lesions and
      hippocampal sclerosis (dual pathology) were excluded from this study. With a mean
      follow-up of 72 months, overall results showed that 84% of group 2 patients
      (Engel's grade Ia) were seizure-free compared with only 47% of group 1 patients.
      Statistical analysis showed that the type of surgical procedure was the main
      prognostic factor. In conclusion, the optimal surgical procedure cannot be
      defined only with the criteria usually retained for temporo-mesial involvement in
      seizure genesis. Taking into account the prognostic value of such implication,
      although complex, is of paramount importance. Our results could be explained by
      the presence of an acquired dual functional pathology.

PMID- 16107083
TI  - [Use of telepathology to provide rapid diagnosis of neurosurgical specimens].
AB  - To determine whether still digital images of neurosurgical specimens sent by e
      mail are an effective and safe way of obtaining an emergency pathological
      diagnosis, representative images from 48 neurosurgical smear specimens were
      digitized, compressed and sent by electronic mail to our consultant
      neuropathologist with relevant clinical and radiological information. The time to
      select, digitize, compress and send the images for each case was recorded.
      Comparison was made between diagnosis made from digital images (DI) and
      historical smear (HS) using the original permanent section (PS) diagnosis as the
      gold standard. A diagnosis of normal vs. abnormal, neoplastic vs. non-neoplastic,
      primary vs. secondary and tumor grade was made in each case. The mean time for
      selection and digitalization of each case was 9.51 minutes. The number of correct
      pathological diagnosis was 41/48 using DI and 48/48 using HS, giving an accuracy
      rate of 85.4% and 100% respectively. DI was 100% sensitive in recognizing
      neoplastic tissue but only 98% specific. Most inaccuracies were in grading and
      caused by problems with field selection and familiarity with the technique. We
      conclude that static digital images are reliable and safe method of interpreting
      tissue during neurosurgical procedures. This corresponds with the findings of
      previous studies.

PMID- 16107084
TI  - Cross-neurotization of the caudal brachial plexus with the contralateral C-8
      ventral nerve branch in the cat. Potential surgical applications, effects of
      graft collection on the healthy donor limb and results.
AB  - Contralateral transfer of the right, eighth ventral nerve branch (C8) (C8 cross
      transfer - C8CT) was performed in 6 adult cats, in which the caudal part of the
      left brachial plexus (C8 and T1) had been severed, in order to mimic nerve root
      avulsion. Clinical and electrophysiological parameters, muscle contraction force
      measurements and histology were used to evaluate the effects of the surgery in a
      14- to 36-month follow-up. The right forelimb (donor side) was clinically normal
      (no lameness) in all the cats at the end of the study. Electromyography performed
      14 days after surgery revealed denervation fibrillation potentials in both
      forelimbs. Fibrillation potentials disappeared in all the cats at the end of the
      study. Direct stimulation of the right C8 ventral branch induced motor and
      sensory evoked potentials in the left limb muscles in all the cats. The left to
      right contraction ratio of the extensor carpi radialis muscle was approximately
      1. This experimental study demonstrates that C8CT enables re-innervation of the
      contralateral brachial plexus and allows the establishment of new functional
      neuromuscular units. This can in turn enable the restoration of function, and
      could potentially lead to partial recovery after caudal brachial plexus avulsion
      in the cat.

PMID- 16107085
TI  - [Idiopathic subarachnoid hemorrhage: is the perimesencephalic distribution that
      benign?].
AB  - INTRODUCTION: Idiopathic subarachnoid hemorrhage (iSAH) is generally recognized
      as benign especially if its distribution is perimesencephalic. In this study we
      assessed the complications following an iSAH and analyzed them in relation to the
      perimesencephalic or diffuse distribution of the hemorrhage. METHOD:
      Retrospective study of 1,148 consecutive patients evaluated between January 1990
      and April 2001 for iSAH documented by cerebral CT-scan with normal cerebral
      angiographic work-up. RESULTS: Of the eighty-seven patients (7.6%) presenting
      with iSAH, 52 presented with a perimesencephalic distribution, and 35 with a
      diffuse distribution. No statistically significant difference was observed
      between the two distributions with regards to complications following the
      hemorrhage, such as hydrocephalus, neurological deficits due to vasospasm,
      systemic effects and mortality. Fisher grade III was associated with an increased
      risk of complications. CONCLUSION: Perimesencephalic iSAH is not exempt from
      complications. Morbidity and mortality in this group are comparable to those
      observed in diffuse iSAH. The Fisher grade is a predicting factor of
      complications for any given hemorrhage distribution.

PMID- 16107086
TI  - [Endovascular treatment of benign intracranial hypertension by stent placement in
      the transverse sinus. Therapeutic and pathophysiological considerations
      illustrated by a case report].
AB  - We report a case of benign intracranial hypertension in a 31-year-old man treated
      by endovascular stent placement in the right transverse sinus. The patient
      presented with a typical benign intracranial hypertension syndrome.
      Ophthalmologic findings showed bilateral papilledema with a 7/10 loss visual
      acuity loss in the right eye and 2/10 in the left eye. At lumbar puncture,
      cerebrospinal fluid (CSF) pressure was 40 mmHg. Magnetic resonance imaging (MRI)
      showed slit ventricles and dilatation of optic nerve sheaths. optiques. After
      failure of medical treatment, the patient was referred to our neurosurgical
      department for therapeutic decision. Direct retrograde cerebral venography showed
      predominant cerebral venous drainage via the right transverse sinus which
      exhibited stenosis in its proximal third. Mamometry revealed a 25 mmHg pressure
      gradient across the point of stenosis. Due to possible venogenic benign
      intracranial hypertension, endovascular stent placement was proposed and accepted
      by the patient. At 3 months follow-up, the patient was symptoms free, papilledema
      had disappeared and visual acuity was 10/10 on both eyes. CSF pressure on lumbar
      puncture was 11 mmHg. The pathophysiological aspects and therapeutic management
      of this pathology illustrated by this are discussed along with a careful and
      exhaustive review of the literature.

PMID- 16107087
TI  - [Emergency surgery of a large ruptured arteriovenous malformation previously
      treated by several embolization procedures].
AB  - A 56-year-old patient with a giant parieto-occipital left-sided arteriovenous
      malformation (AVM) revealed by seizure was treated by four embolization
      procedures. Stereotactic radiosurgery was scheduled for the residual nidus but
      significant intracranial hemorrhage occurred and surgical excision had to be
      performed. The immediate post-operative status was precarious, but the final
      outcome was successful. Therapeutic indications are discussed. A
      multidisciplinary approach for judicious patient selection is surely the key to
      safe overall management of AVMs.

PMID- 16107088
TI  - [Recurrent multiple meningioma and generalized seizure].

PMID- 16107089
TI  - [French neurosurgical practice in neurooncology (national survey--part II).
      Census of current research protocols on brain tumors in France].
AB  - OBJECTIVE: This second part of the inquiry of the NeuroOncolgy Group of the
      French Neurosurgical Society was undertaken to evaluate the involvement of French
      neurosurgeons in brain tumor research. METHODS: In December 2003, A questionnaire
      called "Census of current and future research studies about brain tumors in your
      center" has been mailed to every French neurosurgical department. For each
      protocol, responders were asked to mention: the title of the protocol, its mono-
      or multi-centric design, the name of the principal investigator, the name of the
      neurosurgeon(s) involved in the study, the topic of the study (epidemiology,
      imaging, biology, genetics, therapy), tumor histology, financial support, and
      partners. RESULTS: Twenty-three centers responded. Sixty-three studies were
      described. There were 6 epidemiological studies, 7 imaging studies, 27 biological
      or genetic studies and 15 clinical trials concerning glial tumors, and 8
      biological studies concerning non glial tumors. Each study is described in the
      text with the data previously mentioned. CONCLUSION: Despite the fact that
      several centers did not answer, this inquiry confirmed the strong involvement of
      French neurosurgeons in brain tumor research.

PMID- 16107090
TI  - [Perspectives for aortic endoprostheses].

PMID- 16107091
TI  - [Optimization of carotid endarteriectomy results].

PMID- 16107092
TI  - [Does antiaggregant therapy have a place in type II heparin-induced
      thrombocytopenia?].
AB  - We report a case of type II heparin-induced thrombocytopenia, which occurred
      after heart surgery in a 71-year-old female patient with several cardiovascular
      risk factors. The diagnosis of heparin-induced thrombopenia was suspected because
      association of multifocal arterial and venous thrombosis and detection of
      antiplatelet-factor 4 antibodies with a drop of more than 50% in the platelet
      count. Until diagnostic of heparin-induced thrombocytopenia was made, clopidogrel
      was introduced because of well-documented ischemia in middle-cerebral artery
      territory. The platelets subsequently increased by near 30%. The diagnosis of
      heparin-induced thrombocytopenia was finally confirmed a few days later by
      detection of antiplatelet-factor 4 antibodies associated with a positive platelet
      aggregation test for unfractionated heparin. Heparin was replaced by sodium
      danaparoid. These measures did not change the unfavorable outcome and death of
      the patient. The increase in the platelet count after fortuitous clopidogrel
      introduction raises the question of the role of antiaggregant agents in
      association with anticoagulants for the treatment of type II heparin-induced
      thrombocytopenia.

PMID- 16107093
TI  - [Effects of elastic stockings on venous flow during simple movements and muscular
      contractions of lower limb in healthy volunteers. Pilot study].
AB  - AIM: To study common femoral vein flow during simple movements and voluntary
      contractions of muscles of lower limbs in healthy volunteers and to evaluate the
      effects of elastic stocking on venous flow. METHODOLOGY: Experimental study. Ten
      subjects, aged 21 to 25 years, underwent duplex ultrasound to examine venous
      flow, the lower limb being fitted with sensors to characterize kinematics and of
      muscle activity. MOVEMENTS STUDIED: In supine position: thigh muscles
      contraction. forefoot dorsal flexion. Standing on both feet: thigh muscles
      contraction, tip-toe, front load transfer, extension of the leg on the knee,
      loading on one limb, forefoot back flexion. Data were recorded with a
      computerised system for secondary analysis. A mean venous velocity was calculated
      after elimination of parasite signals. Venous velocity was correlated with muscle
      signals. The procedure was repeated with the patient wearing a thigh-length class
      II elastic stockings (Varisma Innothera Ltd). RESULTS, CONCLUSION: All movements
      increased venous flow. Wearing elastic stockings increased the venous flush due
      to movements or muscle contractions. The level of muscle activity during the same
      movement or the same muscle contraction varied from one subject to the other.

PMID- 16107094
TI  - [Revision of the CEAP classification for venous disorders: consensus statement].

PMID- 16107095
TI  - [Early diagnosis and treatment of transient ischemic events in adults--May 2004].

PMID- 16107096
TI  - [Natural history of intermittent arterial claudication. Bouley-Charcot syndrome].

PMID- 16107097
TI  - [Stiffened triple axial catheterization of tortuous cervivoencephalic vessels].
AB  - Tortuous anatomy of the cervicoencephalic vessels can cause failure in 4 to 6% of
      interventional procedures by slippage of the material back in the aorta, kinking
      or difficulty to move forward a balloon. stent or microcatheter. We report on an
      old patient with high vascular tortuosity, referred for embolization of a
      ruptured aneurysm of the left inferior cerebellar artery. Access wasn't possible
      until we used a "triple axial system" with a long 7F sheath, positioned in the
      left subclavian artery and strongly supported by a super stiff guidewire with its
      distal end floating freely in the vascular lumen. Inside the sheath and parallel
      to the guidewire, we pushed a 4F catheter till the mid-vertebral artery. The
      microcatheter-microguide system tracked through it, towards the aneurysm, with
      the backward tendency being neutralized by the increased stiffness. Our technique
      presents the advantage of a strong back-up support, without increased risks such
      as vasospasm, clotting or dissection, since the guidewire serving as a stiff
      rail, lies exteriorly to the navigated vessel. Efficiency of this elegant and
      relatively low risk solution has yet to be proved in larger series.

PMID- 16107098
TI  - How long will the heart still beat?

PMID- 16107100
TI  - Total arterial coronary bypass: long-term results.
AB  - Three groups of consecutive patients who had undergone primary elective coronary
      artery bypass operations were compared at 10 to 20 years of follow-up (mean, 13.6
      years), in order to test the supposition that arterial conduits provide better
      long-term outcome than do the "standard" left internal mammary-to-left anterior
      descending coronary artery plus saphenous vein bypasses. The arterial group was
      split into groups A (all arterial) and B (2 or more arterial grafts, plus
      saphenous vein grafts). Control group C comprised the standard operations. The
      absence of saphenous vein conduit in group A was associated with fewer angiograms
      for symptoms, fewer reinterventions, and fewer cardiac deaths than those
      experienced in groups B and C. We conclude that the survival and cardiac quality
      of-life advantage found in group A is attributable to the exclusive use of
      arterial conduits.

PMID- 16107099
TI  - Milestones in the treatment of aortic aneurysm: Denton A. Cooley, MD, and the
      Texas Heart Institute.

PMID- 16107101
TI  - Robert DeWitt Leachman: March 18, 1927-April 1, 1996.

PMID- 16107102
TI  - Robotic mitral valve repair: a community hospital experience.
AB  - Robotically assisted cardiac surgery has been presented as less invasive than
      conventional surgery, with shortened hospital stays and faster return to daily
      activities. We evaluated our experience with the da Vinci robot to determine
      whether we could in fact demonstrate those findings. All mitral and tricuspid
      valve repairs were performed by the same surgeon. Cardiopulmonary bypass was
      performed with femoral cannulation, antegrade cardioplegia, and transthoracic
      aortic cross-clamping. Multiple valve repair techniques were used, including
      quadrant resection, cord replacement, Alfieri leaflet coaptation, and ring
      annuloplasty. Access was by 2 ports and a 5-cm right anterolateral thoracotomy.
      All annuloplasty rings were secured using surgical clips. From October 2003
      through September 2004, 32 patients underwent robotically assisted mitral valve
      repair. The mean age of our population was 676 years (range, 43-82 years). Four
      patients also underwent the 1st tricuspid valve repair using the da Vinci robot
      in the United States. There were 3 conversions for irreparable valves, 1 stroke,
      and 2 deaths. The average procedure time, cardiopulmonary bypass time, and aortic
      cross-clamp time were all reduced, when the first 20 patients were compared with
      the last 12. Length-of-stay also improved. One patient required early mitral
      valve replacement for recurrent regurgitation. Two patients required late (> 3
      month) mitral valve replacement for recurrent regurgitation. We have shown that a
      dedicated nonacademic institute can develop a robotic cardiac surgery program and
      perform mitral and tricuspid valve repairs successfully. There is a several-case
      learning curve, and patient selection is paramount.

PMID- 16107103
TI  - Interruption of aortic arch in adults: surgical experience with extra-anatomic
      bypass.
AB  - We reviewed our 3-year experience in treating interruption of the aorta in adult
      patients. Clinical profiles, surgical management, and results of early and mid
      term follow-up are presented. From August 2001 through June 2003, 7 adult
      patients underwent an extra-anatomic bypass procedure to repair interruption of
      the aortic arch. Five patients underwent ventral aortic repair through a mid
      sternotomy and an upper midline laparotomy, and 2 patients underwent repair
      through a left posterolateral thoracotomy. A bovine collagen-impregnated
      polyester fiber graft was used in 6 patients, and a Gore-Tex graft was interposed
      in 1 patient. All repairs were performed without cardiopulmonary bypass. Follow
      up was complete in all patients. The mean follow-up was 1728 +/- 1 months (range,
      9-31 months). No neurologic, renal, or gastrointestinal complications were noted
      in any patient. There was no in-hospital or late mortality or need for re
      intervention. All patients were asymptomatic; however, 5 patients had mild
      residual hypertension. Graft patency in all the patients was confirmed by
      computed tomographic angiography. Interruption of the aorta is rare in adults.
      Ventral aortic repair through a midline approach is our preferred technique for
      surgical repair of this entity, because it avoids the extensive network of
      collateral vessels on the chest wall, enables simultaneous treatment of
      associated lesions, and in all likelihood reduces morbidity and mortality.

PMID- 16107104
TI  - Arch-first technique via clamshell incision: successful surgical reoperation for
      aortic arch dissection.
AB  - We report a case of successful reoperation for aortic arch dissection with use of
      the "arch-first" technique in a patient who had Marfan syndrome. Extracorporeal
      circulation was initiated via right subclavian artery cannulation, and the chest
      was entered through a clamshell incision for the best exposure. When the patient
      was cooled to 18 degrees C, the perfusion was stopped. After the 1st aortic arch
      anastomosis to a 30-mm Dacron graft, cerebral perfusion was reestablished via the
      right subclavian artery. The aortic repair was then completed. The cerebral
      ischemic time was 18 minutes, the aortic cross-clamp time was 69 minutes, and the
      total extracorporeal circulation time was 334 minutes. The patient was discharged
      from the hospital on postoperative day 10 with no neurologic impairment. The arch
      first technique shortens the duration of brain ischemia. When combined with a
      clamshell incision, the technique is particularly helpful for reoperation of the
      aortic arch and thoracic aorta.

PMID- 16107105
TI  - Tracheal stenosis aftertracheostomy or intubation: review with special regard to
      cause and management.
AB  - To investigate the management outcomes of patients who developed tracheal
      stenosis after tracheostomy or intubation, we reviewed the courses of 45 patients
      who had experienced tracheal stenosis at a single institution, over 19 years from
      February 1985 through January 2004. There were 38 tracheal and 7 infraglottic
      stenoses. Twenty-nine stenoses were associated with the stoma, 12 with the cuff,
      and 2 with the endotracheal tube resulting in infraglottic lesions; the remaining
      2 were double stenoses. Eleven patients were treated by bronchoscopic surgery,
      and 34 patients were treated by tracheal or laryngotracheal resection. The
      overall success rate was 93%. The complication rate was 18%. A 2nd operation was
      required in 3 patients, and 1 of the 3 died of sepsis. Our management strategy of
      treating tracheal stenosis with resection and end-to-end anastomosis has been
      associated with good outcomes. Management of infraglottic stenosis is difficult,
      particularly when there is a large laryngeal defect or when there have been
      previous surgical attempts at the same site.

PMID- 16107106
TI  - A new algorithm for preoperative cardiac assessment in patients undergoing
      pulmonary resection.
AB  - From January 2001 through June 2002, 128 consecutive patients undergoing lung
      resection for various diseases were evaluated preoperatively by a cardiologist at
      our institution in order to predict postoperative cardiac complications in
      pulmonary surgery. Our assessment algorithm consisted of the following: Smoking,
      hypertension, hyperlipidemia, advanced age, diabetes mellitus, and history of
      cardiac disease or angina pectoris were considered as risk factors. A stress test
      was performed when at least 2 of the first 3 risk factors or at least 1 of the
      last 3 risk factors was present. Coronary angiography was performed in the case
      of a positive stress test. Patients were classified as low-risk when there was no
      need for a stress test. Patients were considered as intermediate-risk when a
      stress test revealed no ischemia or if there was a history of congestive heart
      failure or valvular disease. Patients in whom coronary artery disease was
      detected on angiography were classified as high-risk. Ninety-five of our patients
      were in the low-risk group, and 29 were in the intermediate-risk group. After
      lung resection, cardiac complications developed in 4 patients in the low-risk
      group (atrial fibrillation) and in 8 patients in the intermediate-risk group (5
      atrial fibrillation and 3 paroxysmal atrial tachycardia). The overall cardiac
      complication rate was 9.7%. No death occurred due to cardiac events. The
      difference in the incidence of arrhythmias between the low- and the intermediate
      risk groups was significant (P < 0.05). We present this simple algorithm for
      preoperative cardiac evaluation in patients scheduled to undergo lung resection,
      and we suggest that it may be possible to predict postoperative cardiac
      complications with this method.

PMID- 16107107
TI  - The relationship between P wave dispersion and diastolic dysfunction.
AB  - We investigated the relationship between P wave dispersion, which is easily
      measured on the surface electrocardiogram and may be used in evaluating the risk
      of atrial fibrillation, and left ventricular diastolic function. There were 133
      patients: 73 with diastolic dysfunction and 60 without. P wave dispersions were
      calculated by measuring minimum and maximum P wave duration values on the surface
      electrocardiogram. The relationships between P wave dispersion and the presence,
      cause, severity, and echocardiographic measurements of diastolic dysfunction were
      investigated. P wave dispersion was 53 +/- 9 ms in patients with diastolic
      dysfunction and 43 +/- 9 ms in the control group (P < 0.01). When patients were
      grouped according to stage of diastolic dysfunction, P wave dispersion was 48 +/-
      7 ms in stage 1, 54 +/- 8 ms in stage 2, and 58 +/- 9 ms in stage 3. As the
      severity of diastolic dysfunction increased, P wave dispersion increased but the
      difference did not reach statistical significance (P < 0.05). When the cause of
      diastolic dysfunction was considered, P wave dispersion was 53 +/- 8 ms in
      patients with ischemic heart disease and 52 +/- 9 ms in patients with left
      ventricular hypertrophy (P > 0.05). We conclude that P wave dispersion increases
      in diastolic dysfunction, but that this increase is not related to the severity
      or cause of diastolic dysfunction. When clinical and echocardiographic variables
      are taken into account, there is a weak but significant correlation only between
      P wave dispersion and left ventricular ejection fraction.

PMID- 16107108
TI  - Thirty-five years of mechanical circulatory support at the Texas Heart Institute:
      an updated overview.
AB  - Since the 1960s, the Texas Heart Institute has been intimately involved in the
      development of mechanical circulatory support devices (for example, ventricular
      assist devices, aortic counterpulsation pumps, and total artificial hearts) for
      both short- and long-term use. Here, we review the varied clinical experience
      with these technologies at the Texas Heart Institute over the last 35 years.

PMID- 16107109
TI  - Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis,
      and management.
AB  - Amyloidosis comprises a unique group of diseases that share in common the
      extracellular deposition of insoluble fibrillar proteins in organs and tissues.
      Cardiovascular amyloidosis can be primary, a part of systemic amyloidosis, or a
      result of chronic systemic diseases elsewhere in the body. The most common
      presentations are congestive heart failure-mainly a restrictive infiltrative
      pattern--and conduction system disturbances. Recent developments in imaging
      techniques and extracardiac tissue sampling have minimized the need for invasive
      endomyocardial biopsy for amyloidosis. Despite advances in treatment, the
      prognosis for patients with amyloidosis is still poor and depends on the
      underlying disease type. Herein, we present new insights and recent advances in
      cardiovascular amyloidosis.

PMID- 16107110
TI  - Surgical treatment of axillary artery aneurysm.
AB  - Aneurysms of the axillary artery are rare and dangerous lesions that threaten the
      upper extremities with vascular and neurologic compromise. Most can be treated
      effectively with surgical excision and vascular grafting. We retrospectively
      assessed 4 axillary artery aneurysms upon which we operated from February 1998
      through March 2004. Three patients were admitted to our clinic for symptomatic
      axillary masses. The remaining patient was transported to our clinic emergently
      due to massive hemorrhage of an enlarging axillary mass that occurred during
      biopsy of the mass at another hospital. In this patient, the ruptured axillary
      artery aneurysm was diagnosed by means of emergent upper-extremity selective
      angiography. All patients were treated surgically by means of aneurysmectomy and
      graft interpositioning--with polytetrafluoroethylene grafts in 2 patients and
      saphenous vein grafts in the other 2. Surgical treatment of axillary artery
      aneurysms is of importance in avoiding thromboembolism and ischemia, which in
      turn can lead to gangrene and amputation of the affected extremity. For this
      reason, operative management of such cases should not be delayed.

PMID- 16107111
TI  - Right axillary artery cannulation for surgical management of the hostile
      ascending aorta.
AB  - Extensive aortic disease, such as atherosclerosis with aneurysms or dissections
      that involve the ascending aorta, can complicate the choice of a cannulation site
      for cardiopulmonary bypass. To date, the standard peripheral arterial cannulation
      site has been the common femoral artery; however, this approach carries the risk
      of atheroembolism due to retrograde aortic perfusion, or it is undesirable
      because of severe iliofemoral disease. Arterial perfusion through the axillary
      artery provides sufficient antegrade aortic flow, is more likely to perfuse the
      true lumen in the event of dissection, and is associated with fewer atheroembolic
      complications. From September 2000 through March 2004, 27 patients underwent
      right axillary artery cannulation for acute ascending aortic dissection (n = 16),
      ascending aortic aneurysm (n = 9), or coronary artery bypass grafting (n = 2).
      Direct artery cannulation was performed in the first 4 patients, and the last 23
      patients were cannulated through a longitudinal arteriotomy via an 8-mm woven
      Dacron graft. Seventeen patients underwent hypothermic circulatory arrest and
      antegrade cerebral perfusion. Two patients died intraoperatively: one due to low
      cardiac output and one due to diffuse bleeding. One patient suffered mild right
      arm paresthesia postoperatively, but recovered completely. Axillary artery
      cannulation was successful in all patients; it provided sufficient arterial flow,
      and there were no intraoperative problems with perfusion. In the presence of
      extensive aortic or iliofemoral disease, arterial perfusion through the axillary
      artery is a safe and effective means of providing sufficient arterial inflow
      during cardiopulmonary bypass. In this regard, it is an excellent alternative to
      standard femoral artery cannulation.

PMID- 16107112
TI  - Recannulation of the right axillary artery for complex aortic surgeries.
AB  - Owing to the increased use of the axillary artery for arterial inflow during
      cardiopulmonary bypass, patients with previous cannulation at this site who
      require reoperation will be encountered more and more frequently. We describe the
      cases of 2 patients who required recannulation of the axillary artery for complex
      reoperations of the thoracic aorta. The technique and pitfalls are described. The
      decision was made to reuse the previous cannulation site at the right axillary
      artery due to the presence of large pseudoaneurysms in proximity to the sternum.
      The old 8-mm Dacron stump was found and excised, and a new 8-mm Dacron graft was
      sutured to the right axillary artery for arterial inflow. In the 1st patient, the
      Dacron side-graft enabled insertion and subsequent inflation of an EndoClamp
      within the Dacron graft of the ascending aorta, which obviated profound
      hypothermia. In the 2nd patient, recannulation of the right axillary artery
      enabled us to open the sternum at low flow using moderate hypothermia, given that
      antegrade cerebral perfusion was easily accessible in the event of a more
      prolonged arrest time. Both patients recovered fully, without neurovascular
      complications secondary to the recannulation of the right axillary. Recannulation
      of the right axillary artery is safe during complex reoperation of the thoracic
      aorta. It avoids retrograde perfusion in the often-diseased descending thoracic
      aorta. Furthermore, sternal reentry may be performed under moderate hypothermia,
      because antegrade cerebral perfusion can be initiated with ease.

PMID- 16107113
TI  - Mechanisms and catheter ablation therapy of atrial fibrillation.

PMID- 16107114
TI  - Mechanisms and catheter ablation of ventricular tachycardia.
AB  - In summary, in patients who have structural heart disease, VT usually originates
      from the left ventricle, is frequently life threatening, and a defibrillator is
      usually required. Ablation can be successful regardless of the hemodynamic
      stability of the tachycardia and usually depends on whether or not one can
      identify the diseased substrate. In the absence of structural heart disease, VT
      usually originates from the right ventricle and oftentimes the outflow tract.
      It's typically not life threatening, and first-line therapy can be either drugs
      or ablation.

PMID- 16107115
TI  - Syncope evaluation and management.

PMID- 16107116
TI  - Patient selection for cardiac resynchronization therapy: how to identify
      responders and non-responders.

PMID- 16107117
TI  - Safe and effective pharmacologic management of arrhythmias.

PMID- 16107118
TI  - Electrical therapy for heart failure: evolving indications and choices.

PMID- 16107119
TI  - Medical management of atrial fibrillation.

PMID- 16107120
TI  - Anticoagulants and atrial fibrillation.

PMID- 16107121
TI  - Intravenous milrinone infusion improves congestive heart failure caused by
      diastolic dysfunction: a brief case series.
AB  - Although there have been significant advances in the medical treatment of heart
      failure patients with impaired systolic function, very little is known about the
      diagnosis and treatment of diastolic dysfunction. We report the cases of 3
      patients in New York Heart Association functional class IV who had
      echocardiographically documented diastolic dysfunction as the main cause of heart
      failure. All 3 patients received medical therapy with long-term milrinone
      infusion.

PMID- 16107122
TI  - Substernal goiter: an unusual cause of respiratory failure after coronary artery
      bypass grafting.
AB  - Substernal goiter can cause extrathoracic upper airway obstruction. Since
      cardiopulmonary bypass results in a systemic inflammatory response syndrome
      characterized by an increase in capillary permeability and edematous changes in
      many tissues including the thyroid gland, an existing nonobstructive substernal
      goiter may become obstructive postoperatively. We describe the case of a patient
      with an asymptomatic substernal goiter who required urgent thyroidectomy for
      tracheal obstruction after elective coronary artery bypass grafting. To the best
      of our knowledge, ours is the 1st such case reported in the English-language
      medical literature. This case illustrates that, in cases of acute postoperative
      respiratory failure after open heart surgery, tracheal obstruction caused by
      enlarged substernal goiter should be considered in the differential diagnosis.

PMID- 16107123
TI  - Pulmonary microthrombi during left ventricular assist device implantation.
AB  - Critically ill heart failure patients undergoing left ventricular assist device
      implantation have alterations in their coagulation profiles; as a result,
      hemorrhagic complications during the postoperative period are the most common and
      serious problems during device support of these patients. The use of aprotinin
      therapy is generally accepted for reducing bleeding after coronary artery bypass
      grafting procedures, heart transplantation, and insertion of a left ventricular
      assist device. We describe the case of a patient who had a suprasystemic increase
      in pulmonary artery pressure, caused by thromboembolic occlusion of the pulmonary
      arterioles after urgent implantation of a left ventricular assist device. The
      complications developed after the patient was weaned from cardiopulmonary bypass
      and heparinization was reversed with protamine. Although the thrombosis was
      successfully reversed with intraoperative administration of tissue plasminogen
      activator directly to the pulmonary artery, the patient died of massive
      hemorrhage 6 hours later. To our knowledge, the direct application of tissue
      plasminogen activator into the pulmonary artery in such a catastrophic situation
      has not been used elsewhere.

PMID- 16107124
TI  - Intracardiac extension of intravenous leiomyoma.
AB  - Intravenous leiomyoma with intracaval and intracardiac extension is a rare benign
      neoplasm affecting women. We report a case in which an intravenous leiomyoma
      originated from the right iliac vein and extended through the inferior vena cava
      into the right atrium. The correct diagnosis was made intraoperatively, after
      resection of the intracardiac extension of the tumor, which was 28 cm in length.
      At the 2nd stage of the operation, a right common iliac venotomy enabled the
      removal of all residual tumor from the inferior vena cava.

PMID- 16107125
TI  - Aortic pseudoaneurysm.
AB  - Reoperative aortic surgery is a therapeutic challenge. We examine a case of
      reoperative aortic surgery involving a pseudoaneurysm that occurred after
      surgical treatment of an abdominal aneurysm. A systematic approach to diagnosis,
      followed by treatment tailored to diagnostic findings, can minimize morbidity.

PMID- 16107126
TI  - Complete embolization of a left atrial myxoma resulting in acute lower extremity
      ischemia.
AB  - Atrial myxoma is the most common benign tumor of the heart. Patients who have
      atrial myoxmas usually present with cardiac obstruction, arrhythmias, or
      peripheral embolization. A tumor originating in the left atrium most often
      embolizes to the cerebrovascular system. Complete myxoma embolization to the
      peripheral vessels is rare and usually occurs with tragic consequences. We
      present an unusual case of acute lower extremity ischemia due to the complete
      embolization of a left atrial myxoma.

PMID- 16107127
TI  - Complete left-sided absence of the pericardium in association with ruptured type
      A aortic dissection complicated by severe left hemothorax.
AB  - We report an unusual clinical presentation of an acute type A aortic dissection
      as a left hemothorax in a patient with a congenital pericardial defect. Although
      the pericardial defect was diagnosed preoperatively, we could not exclude the
      possibility of a ruptured descending aorta until we discovered the site of the
      rupture during operation. The presence of a pericardial defect would at first
      appear to be a fatal disadvantage in such a situation as this, due to massive
      bleeding into the pleural space; but we believe that in our patient spontaneous
      drainage of blood into the pleural cavity prevented severe cardiac tamponade. The
      only reason for his deteriorating hemodynamic status was hypovolemia, which was
      corrected with volume replacement.

PMID- 16107128
TI  - Hyperthyroidism presenting as isolated tricuspid regurgitation and right heart
      failure.
AB  - Although hyperthyroidism has many signs and symptoms, right heart failure can
      occasionally be the main presenting symptom. We describe the case of a previously
      healthy 42-year-old woman whose chief complaint was progressive bilateral lower
      extremity edema. The echocardiogram revealed right atrial dilatation and moderate
      to-severe tricuspid regurgitation. Results of laboratory studies were consistent
      with hyperthyroidism. Thyroid ablation resulted in permanent resolution of
      symptoms and resolution of tricuspid incompetence on echocardiography. In a case
      of isolated, unexplained tricuspid regurgitation, it is important to consider
      indolent hyperthyroidism in the differential diagnosis.

PMID- 16107129
TI  - Use of CT angiography for evaluation of 3 coronary ostia originating from the
      right sinus of Valsalva in a patient with hypertrophic obstructive
      cardiomyopathy.

PMID- 16107130
TI  - Suitability of the internal mammary artery in an adult patient with coarctation
      of the aorta.

PMID- 16107131
TI  - Drawbacks and limitations of computed tomography.

PMID- 16107132
TI  - Peptide hormones and histamine in plasma and synovial fluid of patients with
      rheumatoid arthritis and osteoarthrosis.
AB  - OBJECTIVES: Hormones other than adrenal and gonadal steroids may play also a
      significant role in the pathogenesis of rheumatoid arthritis. The aim of this
      study was to investigate the levels of selected peptide hormones and histamine in
      synovial fluid of knee joints and in plasma of patients with rheumatoid arthritis
      and with osteoarthrosis. METHODS: The concentrations of insulin, C-peptide,
      prolactin, growth hormone, free triiodothyronine (FT3), thyrotropin (TSH), and
      histamine were determined in synovial fluid and plasma of 27 patients with
      rheumatoid arthritis (RA) and in 12 patients with osteoarthrosis (OA). RESULTS:
      The presence of peptide hormones in synovial fluid was demonstrated. The levels
      of TSH and growth hormone were lower in synovial fluid than in plasma in both
      groups, while those of prolactin were comparable in synovial fluid and in plasma.
      The levels of C-peptide (p < 0.05), insulin and FT3 were higher in synovial fluid
      than in plasma of OA patients, but lower in synovial fluid of RA patients as
      compared to their levels in plasma. Significant positive correlations between the
      levels in plasma and synovial fluid were observed in prolactin (p < 0.001, r =
      0.741) and TSH (p < 0.05, r = 0.88) only. After age adjustment, no significant
      differences in synovial fluid and in plasma levels of all hormones were found
      between OA and RA patients. The levels of histamine in plasma were similar in RA
      and OA patients, in synovial fluid of both groups histamine was found in almost
      undetectable amounts. CONCLUSIONS: The selected peptide hormones, e.g. insulin, C
      peptide, prolactin, growth hormone, FT3 and TSH, are present in synovial fluid of
      RA and OA patients, some of them in the concentrations comparable to these in
      plasma. The role of the locally present hormones in pathogenesis of RA has to be
      investigated in further studies and analyses.

PMID- 16107133
TI  - Effect of the growth hormone-releasing hormone [GHRH(1-44)NH2] on IL-6 and IL-8
      secretion from human peripheral blood mononuclear cells in vitro.
AB  - OBJECTIVE: Bidirectional communication between the neuroendocrine and immune
      systems is now a subject of an intensive investigation. Growth hormone-releasing
      hormone (GHRH) is synthesized by the hypothalamus, but is present also in the
      immune cells. Some recent data indicate also an immunomodulatory role of the
      neuropeptide. The aim of the study was to examine the influence of GHRH(1-44)NH2
      on interleukin-6 and interleukin-8 secretion from human peripheral blood
      mononuclear cells cultured in vitro. METHODS: Peripheral blood mononuclear cells
      (PBMC) were isolated by centrifugation using Boyum technique and cultured in a
      humidified atmosphere of 5 % CO2 and 95 % O2 at 37 degrees C for 24 hours in the
      presence of lipopolysaccharide (LPS) at the concentration of 2 microg/ml and
      GHRH(1-44)NH2 (the final neuropeptide concentrations to be tested were 10(-12) to
      10(-6) M). ELISA methods were used to measure IL-6 and IL-8 concentrations in the
      supernatants of cultured cells RESULTS: GHRH(1-44)NH2 influenced IL-6 secretion
      from cultured cells, but significant inhibition of IL-6 release was observed at
      10-6 M (p < 0.001). The negative correlation between the GHRH concentration
      studied and the IL-6 level in the supernatants was found (r = -0.759; p < 0.001).
      GHRH had no influence on the secretion of IL-8 from activated PBMC. CONCLUSIONS:
      Our results demonstrate that GHRH in vitro modulates IL-6 secretion from the
      human peripheral blood mononuclear cells, without any significant effect on IL-8
      secretion.

PMID- 16107134
TI  - Human thyroid in the population exposed to high environmental pollution by
      organochlorinated pollutants for several decades.
AB  - OBJECTIVE: To study possible effects of long-time exposure of chemical factory
      employees and population of surrounding polluted area to polychlorinated
      biphenyls and pesticides on the thyroid volume and function as compared to the
      population from the area of background pollution. METHODS: A total of 461 adults
      consisting of 239 men and 222 women was examined and divided into four groups
      according to their permanent domicile as related to the level of environmental
      pollution, e.g. SR (area of background pollution, n = 207), SI (slightly polluted
      area, n = 59), MI (polluted city of Michalovce, n = 94) and CH (employees of
      chemical factory subjected to high PCB exposure, n = 101), combined first three
      groups being also called LPA (less polluted areas, n = 360). Thyroid volume (ThV)
      and echogenicity were measured by real time sonography. The level of
      polychlorinated biphenyls (PCB) and pesticides (hexachlorbenzene--HCB, DDE (2,2'
      2-bis(4-chlorobiphenyl)- 1,1-dichloroethylene), p,p'-DDT (2,2'-bis(4
      chlorophenyl)- 1,1,1-trichloroethane) and alpha-, beta- and gamma
      hexachlorcyclohexane--HCH) was estimated by congener specific analysis using HP
      5890 gas chromatograph with a 63Ni electron capture detector. Serum levels of
      thyrotropin (TSH) and thyroid peroxidase antibodies (anti-TPO) were measured by
      specific sensitive immunoassays. RESULTS: The association of very high PCB level
      (e.g. 7300 +/- 871 ng/g lipid; mean +/- S.E.) with increased ThV (e.g. 16.3 +/-
      0.73 ml) in CH has been found, the values being significantly higher than these
      of 360 subjects in LPA (e.g. 2045 +/- 147 ng/g, p < 0.001 for PCB and 14.0 +/-
      0.32 ml, p < 0.001 for ThV). In 23 subjects from CH with PCB level > 10000 ng/g
      the ThV was 18.7 +/- 2.32 ml, while that in 251 subjects from LPA with PCB level
      of < 2000 ng/g was 13.8 +/- 0.35 ml (p < 0.05). In addition, ThV as well as PCB
      levels were strikingly increasing with age. In parallel with PCB levels, also the
      levels of other organochlorines estimated (namely these of DDE) were increasing.
      Although the participation of these substances in the development of adverse
      effects cannot yet be defined, it cannot be excluded. The association of
      increased levels of episodic congener PCB 101 with increased ThV appeared to be
      more pronounced than that of stable congeners PCB 153 and 180. Finally,
      significant increase in the frequency of thyroid hypoechogenicity by ultrasound,
      ThV > 20.0 ml and thyroperoxidase antibodies in CH area was observed as compared
      to LPA. CONCLUSIONS: Several associations of high PCB and pesticides level with
      characteristics of thyroid disorders (e.g. increased thyroid volume, frequency of
      hypoechogenicity and frequency of positive thyroperoxidase antibodies level in
      blood) were observed in the area with heavy industrial pollution by PCB.

PMID- 16107135
TI  - Ovarian intrafollicular processes as a target for cigarette smoke components and
      selected environmental reproductive disruptors.
AB  - Steroidogenesis, expansion of oocyte-cumulus complex, and meiotic maturation of
      the oocyte represent intrafollicular processes taking important part in the
      background of successful fertilisation. The reproductive health of female could
      be affected by a number of endogenous as well as exogenous factors, such as
      exposure to agents from specific lifestyle habits, environmental pollutants with
      endocrine disrupting properties, or heavy metals. Published data indicate that
      exposure to chemicals may cause alterations in reproductive behavior and
      contribute to sub-fecundity, infertility, or ovarian failure. Female reproductive
      functions can be compromised by exposure to toxic chemicals at a variety of
      sites, including ovary or reproductive tract. Substantial harmful effects of
      cigarette smoke on fecundity and reproduction have become apparent but are not
      generally appreciated. The effects of cigarette smoke components (cadmium,
      nicotine, cotinine) absorbed into the organism on intrafollicular processes may
      thus in part explain the negative impact of smoking on female fertility.
      Moreover, it is now evident that a variety of man-made pollutants present in the
      environment are capable to disrupt normal endocrine function in many species.
      Examples of these "endocrine disrupters" include plasticizers, such as phthalates
      and bisphenol A. The effects of selected environmental chemicals on the processes
      of steroidogenesis, expansion of oocyte-cumulus complex, and meiotic maturation
      of the oocyte are summarized in the present paper and possible mechanisms of
      action of these agents are suggested. However, for complete understanding the
      mechanisms by which chemical agents from the environment can affect the
      intrafollicular processes, a lot of further investigation is needed.

PMID- 16107136
TI  - Farnesoid X receptor: from structure to potential clinical applications.

PMID- 16107137
TI  - Synthesis and characterization of a small, membrane-permeant, caspase-activatable
      far-red fluorescent peptide for imaging apoptosis.
AB  - To image apoptosis in vivo with a small, membrane-permeant probe, TcapQ(647) was
      synthesized comprising a Tat-peptide-based permeation peptide sequence, an
      effector caspase recognition sequence, DEVD, and a flanking optically activatable
      pair comprising a far-red quencher, QSY 21, and a fluorophore, Alexa Fluor 647.
      Under baseline conditions, high quenching efficiencies were observed resulting in
      low background fluorescence. Upon exposure to executioner caspases, TcapQ(647)
      was specifically cleaved, thereby releasing the fluorophore from the quencher and
      enabling imaging of apoptosis.

PMID- 16107138
TI  - A molecular target for suppression of the evolution of antibiotic resistance:
      inhibition of the Escherichia coli RecA protein by N(6)-(1-naphthyl)-ADP.
AB  - We report that N(6)-(1-naphthyl)-ADP inhibits the Escherichia coli RecA protein
      in vitro. A novel rapid screen identified it as a potent inhibitor of RecA
      nucleoprotein filament formation, and further characterization established it as
      an ATP-competitive inhibitor of RecA-catalyzed ATP hydrolysis. This and other
      inhibitors of RecA activities represent a new approach for understanding the
      molecular targets and pathways involved in the evolution of antibiotic resistance
      in bacteria.

PMID- 16107139
TI  - Indolin-2-ones with high in vivo efficacy in a model for multiple sclerosis.
AB  - The known KDR inhibitor SU5416 and several analogues of the indolin-2-one family
      were surprisingly found to be highly efficacious in the EAE model, an established
      model for multiple sclerosis. The high in vivo effect could be correlated to in
      vitro inhibition of the pro-inflammatory cytokine IL-2. Activity following po
      administration was obtained with several analogues and via the use of prodrugs.

PMID- 16107140
TI  - The protein farnesyltransferase inhibitor Tipifarnib as a new lead for the
      development of drugs against Chagas disease.
AB  - Tipifarnib (R115777), an inhibitor of human protein farnesyltransferase (PFT), is
      shown to be a highly potent inhibitor of Trypanosoma cruzi growth (ED(50) = 4
      nM). Surprisingly, this is due to the inhibition of cytochrome P450 sterol 14
      demethylase (CYP51, EC 1.14.13.70). Homology models of the T. cruzi CYP51 were
      used for the prediction of the binding modes of the substrate lanosterol and of
      Tipifarnib, providing a basis for the design of derivatives with selectivity for
      TcCYP51 over human PFT.

PMID- 16107141
TI  - Discovery of substituted maleimides as liver X receptor agonists and
      determination of a ligand-bound crystal structure.
AB  - Substituted 3-(phenylamino)-1H-pyrrole-2,5-diones were identified from a high
      throughput screen as inducers of human ATP binding cassette transporter A1
      expression. Mechanism of action studies led to the identification of GSK3987 as
      an LXR ligand. GSK3987 recruits the steroid receptor coactivator-1 to human
      LXRalpha and LXRbeta with EC(50)s of 40 nM, profiles as an LXR agonist in
      functional assays, and activates LXR though a mechanism that is similar to first
      generation LXR agonists.

PMID- 16107142
TI  - Mapping antimalarial pharmacophores as a useful tool for the rapid discovery of
      drugs effective in vivo: design, construction, characterization, and pharmacology
      of metaquine.
AB  - Resistant strains of Plasmodium falciparum and the unavailability of useful
      antimalarial vaccines reinforce the need to develop new efficacious
      antimalarials. This study details a pharmacophore model that has been used to
      identify a potent, soluble, orally bioavailable antimalarial bisquinoline,
      metaquine (N,N'-bis(7-chloroquinolin-4-yl)benzene-1,3-diamine) (dihydrochloride),
      which is active against Plasmodium berghei in vivo (oral ID(50) of 25
      micromol/kg) and multidrug-resistant Plasmodium falciparum K1 in vitro (0.17
      microM). Metaquine shows strong affinity for the putative antimalarial receptor,
      heme at pH 7.4 in aqueous DMSO. Both crystallographic analyses and quantum
      mechanical calculations (HF/6-31+G) reveal important regions of protonation and
      bonding thought to persist at parasitic vacuolar pH concordant with our receptor
      model. Formation of drug-heme adduct in solution was confirmed using high
      resolution positive ion electrospray mass spectrometry. Metaquine showed strong
      binding with the receptor in a 1:1 ratio (log K = 5.7 +/- 0.1) that was predicted
      by molecular mechanics calculations. This study illustrates a rational
      multidisciplinary approach for the development of new 4-aminoquinoline
      antimalarials, with efficacy superior to chloroquine, based on the use of a
      pharmacophore model.

PMID- 16107143
TI  - A combination of docking, QM/MM methods, and MD simulation for binding affinity
      estimation of metalloprotein ligands.
AB  - To alleviate the problems in the receptor-based design of metalloprotein ligands
      due to inadequacies in the force-field description of coordination bonds, a four
      tier approach was devised. Representative ligand-metalloprotein interaction
      energies are obtained by subsequent application of (1) docking with metal-binding
      guided selection of modes, (2) optimization of the ligand-metalloprotein complex
      geometry by combined quantum mechanics and molecular mechanics (QM/MM) methods,
      (3) conformational sampling of the complex with constrained metal bonds by force
      field-based molecular dynamics (MD), and (4) a single point QM/MM energy
      calculation for the time-averaged structures. The QM/MM interaction energies are,
      in a linear combination with the desolvation-characterizing changes in the
      solvent-accessible surface areas, correlated with experimental data. The approach
      was applied to structural correlation of published binding free energies of a
      diverse set of 28 hydroxamate inhibitors to zinc-dependent matrix
      metalloproteinase 9 (MMP-9). Inclusion of steps 3 and 4 significantly improved
      both correlation and prediction. The two descriptors explained 90% of variance in
      inhibition constants of all 28 inhibitors, ranging from 0.08 to 349 nM, with the
      average unassigned error of 0.318 log units. The structural and energetic
      information obtained from the time-averaged MD simulation results helped
      understand the differences in binding modes of related compounds.

PMID- 16107144
TI  - Virtual screening of biogenic amine-binding G-protein coupled receptors:
      comparative evaluation of protein- and ligand-based virtual screening protocols.
AB  - In this paper, we compare protein- and ligand-based virtual screening techniques
      for identifying the ligands of four biogenic amine-binding G-protein coupled
      receptors (GPCRs). For the screening of the virtual compound libraries, we used
      (1) molecular docking into GPCR homology models, (2) ligand-based pharmacophore
      and Feature Tree models, (3) three-dimensional (3D)-similarity searches, and (4)
      statistical methods [partial least squares (PLS) and partial least squares
      discriminant analysis (PLS-DA) models] based on two-dimensional (2D) molecular
      descriptors. The comparison of the different methods in retrieving known
      antagonists from virtual libraries shows that in our study the ligand-based
      pharmacophore-, Feature Tree-, and 2D quantitative structure-activity
      relationship (QSAR)-based screening techniques provide enrichment factors that
      are higher than those provided by molecular docking into the GPCR homology
      models. Nevertheless, the hit rates achieved when docking with GOLD and ranking
      the ligands with GoldScore (up to 60% among the top-ranked 1% of the screened
      databases) are still satisfying. These results suggest that docking into GPCR
      homology models can be a useful approach for lead finding by virtual screening
      when either little or no information about the active ligands is available.

PMID- 16107145
TI  - Improving binding mode predictions by docking into protein-specifically adapted
      potential fields.
AB  - The development of a protein-specifically adapted objective function for docking
      is described. Structural and energetic information about known protein-ligand
      complexes is exploited to tailor knowledge-based potentials using a "reverse",
      protein-based CoMFA-type (=AFMoC) approach. That way, effects due to protein
      flexibility and information about multiple solvation schemes can be implicitly
      incorporated. Compared to the application of AFMoC for binding affinity
      predictions, a Shannon entropy based column filtering of the descriptor matrix
      and the capping of adapted repulsive potentials within the binding site have
      turned out to be crucial for the success of this method. The new developed
      approach (AFMoC(obj)) was validated on a data set of 66 HIV-1 protease
      inhibitors, for which experimental structural information was available.
      Convincingly, for ligands with up to 20 rotatable bonds, in more than 75% of all
      cases a binding mode below 2 A rmsd has been identified on the first scoring rank
      when AFMoC(obj)-based potentials were used as the objective function in AutoDock.
      With respect to nonadapted DrugScore or AutoDock fields, the binding mode
      prediction accuracy was significantly improved by 14%. Noteworthy, very similar
      results were obtained for training and test set compounds, demonstrating the
      strength and robustness of this method. Implications of our findings for binding
      affinity predictions and its usage in virtual screening are further discussed.

PMID- 16107146
TI  - Synthesis, DNA affinity, and antiprotozoal activity of fused ring dicationic
      compounds and their prodrugs.
AB  - Dicationic guanidine, N-alkylguanidine, and reversed amidine derivatives of fused
      ring systems have been synthesized from their corresponding bis-amines. DNA
      binding studies suggest that the diguanidines and the N-alkyl diguanidines
      fluorenes bind in the minor groove in a manner similar to that of the previously
      reported dicationic carbazole derivatives. The diguanidines and the N-alkyl
      diguanidines showed promising in vitro activity against both Trypanosoma brucei
      rhodesiense and Plasmodium falciparum. Promising in vivo biological results were
      obtained for the dicationic N-isopropylguanidino-9H-fluorene, giving 4/4 cures of
      the treated animals in the STIB900 animal model for African trypanosomiasis. The
      N-methyl analogue showed high activity as well. In addition, with the goal of
      enhancing the oral bioavailability, two novel classes of potential guanidine
      prodrugs were prepared. The N-alkoxyguanidine derivatives were not effective as
      prodrugs. In contrast, a number of the carbamates showed promising activity. The
      value of the carbamate prodrugs was clearly demonstrated by the results, which
      gave 4/4 cures on oral administration in the STIB900 mouse model.

PMID- 16107147
TI  - Development of a three-dimensional model for the N-methyl-D-aspartate NR2A
      subunit.
AB  - NR2 subunits of N-methyl-d-aspartic acid (NMDA) receptors are known to bind the
      neurotransmitter glutamate, competitive agonists, and antagonists. Since
      crystallographic data of these proteins are not available, we built a homology
      model of the ligand binding domain of the NR2A subunit. A consensus binding mode
      of selected AP5-like NMDA antagonists has been ascertained using molecular
      docking. The present 3D model gives insights for the design of new NMDA subtype
      selective compounds.

PMID- 16107148
TI  - New 5-hydroxytryptamine(1A) receptor ligands containing a norbornene nucleus:
      synthesis and in vitro pharmacological evaluation.
AB  - New arylpiperazine derivatives were prepared to identify highly selective and
      potent ligands for the 5-hydroxytryptamine 1A (5-HT(1A)) receptor as potential
      pharmacological tools in studies of central nervous system (CNS) disorders. The
      combination of structural elements (heterocyclic nucleus, oxyalkyl chain, and
      arylpiperazine) known to introduce 5-HT(1A) receptor affinity and the proper
      selection of substituents led to compounds with higher receptor specificity and
      affinity. In binding studies, several molecules showed affinity in the nanomolar
      and subnanomolar ranges at 5-HT(1A) and moderate to no affinity for other
      relevant receptors (5-HT(2A), 5-HT(2C), D(1), D(2), alpha(1), and alpha(2)). The
      4-[3-[4-(o-methoxyphenyl)piperazin-1-yl]propoxy]-4-aza-tricyclo[5.2.1.02,6]dec-8
      ene-3,5-dione, with K(i) = 0.021 nM, was the most active and selective derivative
      for the 5-HT(1A) receptor with respect to other serotonin receptors, whereas the
      most selective derivative for dopaminergic and adrenergic receptors was a CF(3)
      substituted arylpiperazine. As a general trend, compounds with a
      piperazinylpropoxy chain showed a preferential affinity for the 5-HT(1A)
      receptor, suggesting that the alkyl chain length represents a critical structural
      feature in determining 5-HT(1A) receptor affinity and selectivity, as confirmed
      by the molecular modeling invoked for explaining the differential binding
      affinities of the new arylpiperazines.

PMID- 16107149
TI  - Design, synthesis, and antiviral activity of 2'-deoxy-2'-fluoro-2'-C
      methylcytidine, a potent inhibitor of hepatitis C virus replication.
AB  - The pyrimidine nucleoside beta-d-2'-deoxy-2'-fluoro-2'-C-methylcytidine (1) was
      designed as a hepatitis C virus RNA-dependent RNA polymerase (HCV RdRp)
      inhibitor. The title compound was obtained by a DAST fluorination of N(4)-benzoyl
      1-(2-methyl-3,5-di-O-benzoyl-beta-d-arabinofuranosyl]cytosine to provide N(4)
      benzoyl-1-[2-fluoro-2-methyl-3,5-di-O-benzoyl-beta-d-ribofuranosyl]cytosine. The
      protected 2'-C-methylcytidine was obtained as a byproduct from the DAST
      fluorination and allowed for the preparation of two biologically active compounds
      from a common precursor. Compound 1 and 2'-C-methylcytidine were assayed in a
      subgenomic HCV replicon assay system and found to be potent and selective
      inhibitors of HCV replication. Compound 1 shows increased inhibitory activity in
      the HCV replicon assay compared to 2'-C-methylcytidine and low cellular toxicity.

PMID- 16107150
TI  - Synthesis, biological evaluation, and molecular modeling investigation of new
      chiral fibrates with PPARalpha and PPARgamma agonist activity.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors that govern lipid and glucose homeostasis playing a central
      role in cardiovascular diseases, obesity, and diabetes. Medications targeted to
      PPARs have been established to treat hyperlipidemia (fibrates) and insulin
      resistance (glitazones). Thus, there is significant interest in developing new
      and specific ligands for these receptors. Here, we present the results of the
      screening of new ligands of PPARalpha and PPARgamma. Optical isomers of new
      chiral fibrates were synthesized and tested in cell-based assays. Compound (S)-7
      showed a dual PPARalpha/gamma activity, and its stereochemistry was crucial in
      receptor activation. Protease protection experiments suggested that this compound
      binds directly to PPAR. Moreover, computational studies showed that it properly
      docks to PPARalpha and gamma ligand binding pockets. Interestingly, (S)-7
      exhibited only a modest capacity to induce the differentiation of murine
      fibroblasts 3T3-L1 into adipocytes compared to rosiglitazone, a well-known
      PPARgamma agonist.

PMID- 16107151
TI  - From small sweeteners to sweet proteins: anatomy of the binding sites of the
      human T1R2_T1R3 receptor.
AB  - The sweet taste receptor, a heterodimeric G protein coupled receptor (GPCR)
      protein, formed by the T1R2 and T1R3 subunits, recognizes several sweet compounds
      including carbohydrates, amino acids, peptides, proteins, and synthetic
      sweeteners. Its similarity with the metabotropic glutamate mGluR1 receptor
      allowed us to build homology models. All possible dimers formed by combinations
      of the human T1R2 and T1R3 subunits, modeled on the A (closed) or B (open) chains
      of the extracellular ligand binding domain of the mGluR1 template, yield four
      ligand binding sites for low-molecular-weight sweeteners. These sites were probed
      by docking a set of molecules representative of all classes of sweet compounds
      and calculating the free energy of ligand binding. These sites are not easily
      accessible to sweet proteins, but docking experiments in silico showed that sweet
      proteins can bind to a secondary site without entering the deep cleft. Our models
      account for many experimental observations on the tastes of sweeteners, including
      sweetness synergy, and can help to design new sweeteners.

PMID- 16107152
TI  - Structure-based optimization of phenylbutyrate-derived histone deacetylase
      inhibitors.
AB  - Previously, we developed a strategy to develop a novel class of histone
      deacetylase (HDAC) inhibitors by tethering short-chain fatty acids with Zn(2+)
      chelating motifs, which led to N-hydroxy-4-(4-phenylbutyryl-amino)benzamide
      (HTPB), a hydroxamate-tethered phenylbutyrate derivative with sub-micromolar
      potency in inhibiting HDAC activity and cancer cell proliferation. In this study,
      we carried out structure-based optimization of HTPB by using the framework
      generated by the structure of histone deacetylase-like protein (HDLP)
      trichostatin A (TSA) complexes. Docking of HTPB into the HDLP binding domain
      suggested that the hydrophobic microenvironment encompassed by Phe-198 and Phe
      200 could be exploited for structural optimization. This premise was corroborated
      by the greater potency of (S)-(+)-N-hydroxy-4-(3-methyl-2-phenylbutyrylamino)
      benzamide [(S)-11] (IC(50) in HDAC inhibition, 16 nM), of which the isopropyl
      moiety was favorable in interacting with this hydrophobic motif. (S)-11 at
      concentrations as low as 0.1 microM was effective in causing histone
      hyperacetylation and p21(WAF/CIP1) overexpression and suppressing proliferation
      in cancer cells.

PMID- 16107153
TI  - Structure of aldehyde reductase holoenzyme in complex with the potent aldose
      reductase inhibitor fidarestat: implications for inhibitor binding and
      selectivity.
AB  - Structure determination of porcine aldehyde reductase holoenzyme in complex with
      the potent aldose reductase inhibitor fidarestat was carried out to explain the
      difference in the potency of the inhibitor for aldose and aldehyde reductases.
      The hydrogen bonds between the active-site residues Tyr50, His113, and Trp114 and
      fidarestat are conserved in the two enzymes. In aldose reductase, Leu300 forms a
      hydrogen bond through its main-chain nitrogen atom with the exocyclic amide group
      of the inhibitor, which when replaced with a Pro in aldehyde reductase, cannot
      form a hydrogen bond, thus causing a loss in binding energy. Furthermore, in
      aldehyde reductase, the side chain of Trp220 occupies a disordered split
      conformation that is not observed in aldose reductase. Molecular modeling and
      inhibitory activity measurements suggest that the difference in the interaction
      between the side chain of Trp220 and fidarestat may contribute to the difference
      in the binding of the inhibitor to the enzymes.

PMID- 16107154
TI  - Inhibition of carboxylesterases by benzil (diphenylethane-1,2-dione) and
      heterocyclic analogues is dependent upon the aromaticity of the ring and the
      flexibility of the dione moiety.
AB  - Benzil has been identified as a potent selective inhibitor of carboxylesterases
      (CEs). Essential components of the molecule required for inhibitory activity
      include the dione moiety and the benzene rings, and substitution within the rings
      affords increased selectivity toward CEs from different species. Replacement of
      the benzene rings with heterocyclic substituents increased the K(i) values for
      the compounds toward three mammalian CEs when using o-nitrophenyl acetate as a
      substrate. Logarithmic plots of the K(i) values versus the empirical resonance
      energy, the heat of union of formation energy, or the aromatic stabilization
      energy determined from molecular orbital calculations for the ring structures
      yielded linear relationships that allowed prediction of the efficacy of the
      diones toward CE inhibition. Using these data, we predicted that 2,2'-naphthil
      would be an excellent inhibitor of mammalian CEs. This was demonstrated to be
      correct with a K(i) value of 1 nM being observed for a rabbit liver CE. In
      addition, molecular simulations of the movement of the ring structures around the
      dione dihedral indicated that the ability of the compounds to inhibit CEs was
      due, in part, to rotational constraints enforced by the dione moiety. Overall,
      these studies identify subdomains within the aromatic ethane-1,2-diones, that are
      responsible for CE inhibition.

PMID- 16107155
TI  - Defunctionalized lobeline analogues: structure-activity of novel ligands for the
      vesicular monoamine transporter.
AB  - (-)-Lobeline (2R,6S,10S), an antagonist at nicotinic acetylcholine receptors
      (nAChRs), inhibits the neurochemical and behavioral effects of methamphetamine
      and inhibits dopamine transporter (DAT) and vesicular monoamine transporter
      (VMAT2) function. VMAT2 is a target for the development of treatments for
      methamphetamine abuse. Structural modification of lobeline affords the
      defunctionalized analogues meso-transdiene (MTD) and lobelane, which have high
      potency and selectivity for VMAT2. To establish the structure-activity
      relationships within this novel class of VMAT2 ligands, specific stereochemical
      forms of MTD, lobelane, and other structurally related analogues have been
      synthesized. These compounds have been evaluated for inhibition of [(3)H]nicotine
      ([(3)H]NIC) binding (alpha4beta2 nAChR), [(3)H]methyllycaconitine ([(3)H]MLA)
      binding (alpha7 nAChR), and [(3)H]dihydrotetrabenazine ([(3)H]DTBZ) binding
      (VMAT2). Generally, all of these analogues had lower affinities at alpha4beta2
      and alpha7 nAChRs compared to lobeline, thereby increasing selectivity for VMAT2.
      The following structural modifications resulted in only modest changes in
      affinity for VMAT2, affording analogues that were less potent than the lead
      compound, lobelane: (1) altering the stereochemistry at the C-2 and C-6 positions
      of the piperidino ring, (2) varying unsaturation in the piperidino C-2 and C-6
      substituents, (3) introducing unsaturation into the piperidine ring, (4) ring
      opening or eliminating the piperidine ring, and (5) removing the piperidino N
      methyl group. Furthermore, incorporating a quaternary ammonium group into
      defunctionalized lobeline molecules in the cis-series resulted in significant
      loss of affinity for VMAT2, whereas only a modest change in affinity was obtained
      in the trans-series. The most potent (K(i) = 630 nM) and VMAT2-selective compound
      evaluated was the N-methyl-2,6-cis-bis(naphthaleneethyl)piperidine analogue (1
      NAP-lobelane), in which the phenyl groups of lobelane were replaced with 1
      naphthyl moieties. Thus, initial structure-activity relationship studies reveal
      that the most promising structural changes to the lobeline molecule that lead to
      enhancement of VMAT2 affinity and selectivity are defunctionalization, affording
      lobelane and MTD, and replacement of the phenyl rings of lobelane with other
      aromatic moieties that have a pi-extended structure.

PMID- 16107156
TI  - QSAR studies of copper azamacrocycles and thiosemicarbazones: MM3 parameter
      development and prediction of biological properties.
AB  - Genetic algorithms (GA) were used to develop specific copper metal-ligand force
      field parameters for the MM3 force field, from a combination of crystallographic
      structures and ab initio calculations. These new parameters produced results in
      good agreement with experiment and previously reported copper metal-ligand
      parameters for the AMBER force field. The MM3 parameters were then used to
      develop several quantitative structure-activity relationship (QSAR) models. A
      successful QSAR for predicting the lipophilicity (log P(ow)) of several classes
      of Cu(II)-chelating ligands was built using a training set of 32 Cu(II)
      radiometal complexes and 6 simple molecular descriptors. The QSAR exhibited a
      correlation between the predicted and experimental log P(ow) with an r(2) = 0.95,
      q(2) = 0.92. When applied to an external test set of 11 Cu(II) complexes, the
      QSAR preformed with great accuracy; r(2) = 0.93 and a q(2) = 0.91 utilizing a
      leave-one-out cross-validation analysis. Additional QSAR models were developed to
      predict the biodistribution of a smaller set of Cu(II) bis(thiosemicarbazone)
      complexes.

PMID- 16107157
TI  - Design and synthesis of a series of melamine-based nitroheterocycles with
      activity against Trypanosomatid parasites.
AB  - The parasites that give rise to human African trypanosomiasis (HAT) are
      auxotrophs for various nutrients from the human host, including purines. They
      have specialist nucleoside transporters to import these metabolites. In addition
      to uptake of purine nucleobases and purine nucleosides, one of these
      transporters, the P2 transporter, can carry melamine derivatives; these
      derivatives are not substrates for the corresponding mammalian transporters. In
      this paper, we report the coupling of the melamine moiety to selected nitro
      heterocycles with the aim of selectively delivering these compounds to the
      parasites. Some compounds prepared have similar in vitro trypanocidal activities
      as melarsoprol, the principal drug used against late-stage HAT, with 50% growth
      inhibitory concentrations in the submicromolar range. Selected compounds were
      also evaluated in vivo in rodent models infected with Trypanosoma brucei brucei
      and T. brucei rhodesiense and showed pronounced activity and in two cases were
      curative without overt signs of toxicity. Compounds were also tested against
      other trypanosomatid pathogens, Leishmania donovani and Trypanosoma cruzi, and
      significant activity in vitro was noted for T. cruzi against which various nitro
      heterocycles are already registered for use.

PMID- 16107158
TI  - Novel 8-substituted dipyridodiazepinone inhibitors with a broad-spectrum of
      activity against HIV-1 strains resistant to non-nucleoside reverse transcriptase
      inhibitors.
AB  - A series of novel 8-substituted dipyridodiazepinone-based inhibitors were
      investigated for their antiviral activity against wild type human
      immunodeficiency virus (HIV-1) and the clinically prevalent K103N/Y181C mutant
      virus. Our efforts have resulted in a series of benzoic acid analogues that are
      potent inhibitors of HIV-1 replication against a panel of HIV-1 strains resistant
      to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Furthermore, the
      combination of good antiviral potency, a broad spectrum of activity, and an
      excellent pharmacokinetic profile provides strong justification for the further
      development of compound (7) as a potential treatment for wild type and NNRTI
      resistant HIV-1 infection.

PMID- 16107159
TI  - Novel 2,3-dihydrobenzofuran-2-carboxylic acids: highly potent and subtype
      selective PPARalpha agonists with potent hypolipidemic activity.
AB  - The design and synthesis of a novel class of 2,3-dihydrobenzofuran-2-carboxylic
      acids as highly potent and subtype-selective PPARalpha agonists are reported.
      Systematic study of structure-activity relationships has identified several key
      structural elements within this class for maintaining the potency and subtype
      selectivity. Select compounds were evaluated in animal models of dyslipidemia
      using Syrian hamsters and male Beagle dogs, and all these compounds displayed
      excellent cholesterol- and triglyceride-lowering activity at dose levels that
      were much lower than the marketed weak PPARalpha agonist fenofibrate.

PMID- 16107160
TI  - 2-[(Carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids selectively suppressed
      proliferation of neoplastic human HeLa cells. A SAR/QSAR study.
AB  - A series of twenty alkyl-, halo-, and methoxy-aryl-substituted 2
      [(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids were synthesized. The new
      compounds, called CSAB, suppressed proliferation of human cervix carcinoma, HeLa
      cells, in vitro in a concentration range of 0.644 to 29.48 microM/L. Two
      compounds exhibit antiproliferative activity in sub-micromolar concentrations.
      Five compounds act in low micromolar concentrations (<2 microM/L). The most
      active compounds exert lower cytotoxicity toward healthy human peripheral blood
      mononuclear cells (PBMC and PBMC+PHA) (selectivity indexes > 10). A strong
      structure-activity relationship, using estimated log P values and BCUT
      descriptors, was observed.

PMID- 16107161
TI  - Antitumor activity of new substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2
      indolinones and study of their effect on the cell cycle.
AB  - This paper reports the synthesis of a new series of 3-(5-imidazo[2,1
      b]thiazolylmethylene)-2-indolinones which were tested as potential antitumor
      agents at the National Cancer Institute. Two derivatives are now under review by
      BEC (Biological Evaluation Committee of NCI). To investigate the mechanism of
      action, the effect on cell cycle progression was studied by monitoring them in
      colon adenocarcinoma HT-29: both were able to block HT-29 in mitosis. 3-[(2,6
      Dimethylimidazo[2,1-b]thiazol-5-yl)methylene]-5-chloro-2-indolinone was the most
      active compound.

PMID- 16107162
TI  - From the potent and selective mu opioid receptor agonist H-Dmt-d-Arg-Phe-Lys
      NH(2) to the potent delta antagonist H-Dmt-Tic-Phe-Lys(Z)-OH.
AB  - H-Dmt-d-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA) binds with high affinity and
      selectivity to the mu opioid receptor and is a potent and long-acting analgesic.
      Substitution of d-Arg in position 2 with Tic and masking of the lysine amine side
      chain by Z protection and of the C-terminal carboxylic function instead of the
      amide function transform a potent and selective mu agonist into a potent and
      selective delta antagonist H-Dmt-Tic-Phe-Lys(Z)-OH. Such a delta antagonist could
      be used as a pharmacological tool.

PMID- 16107163
TI  - [Clinical cases in medical mycology. Case No. 17].

PMID- 16107164
TI  - [Lichens as rapid bioindicators of pollution and habitat disturbances in the
      tropics].
AB  - Lichens have value as bioindicators of environmental pollution, climate change,
      and ecological continuity. Extensive work has been undertaken in temperate areas,
      but in only few cases have the techniques been applied in the tropics. Most
      tropical studies to date are in relation to air pollution and forest disturbance,
      but these are scattered geographically and remain to be undertaken in most
      tropical regions. The potential of lichens as rapid bioindicators in the tropics
      can start to be realized even where the species described are not fully
      identified as they are perennial and separable by eye or hand lens, and a lack of
      training is identified as the main constraint. An extensive bibliography is
      included.

PMID- 16107165
TI  - Point prevalence, microbiology and antifungal susceptibility patterns of oral
      Candida isolates colonizing or infecting Mexican HIV/AIDS patients and healthy
      persons.
AB  - We have conducted a longitudinal study over a 3-year period to address the point
      prevalence, microbiological characteristics and antifungal susceptibility
      patterns of yeast isolates colonizing or infecting the oral cavities of 111 HIV
      infected (51 adults, 60 children) and 201 non HIV-infected (109 adults, 92
      children) Mexican persons. Regarding the epidemiology of oral candidiasis,
      Candida albicans was the most frequent species isolated. Seventy-one out of 85
      isolates from colonized persons were C. albicans (83.5%), 27 isolates of them
      were from HIV-infected children and 44 from non HIV-infected patients. Sixty-two
      isolates belonged to serotype A which was the most prevalent serotype of C.
      albicans. Non-albicans species (Candida glabrata, Candida tropicalis and Candida
      parapsilosis, and Saccharomyces cerevisiae) were isolated from 16.5% of colonized
      patients and from 38.5% patients with candidiasis or Candida-related lesions.
      There were nine episodes of infection or colonization by at least 2 different
      yeast species. In the case of HIV/AIDS patients, it was determined that yeast
      carriage was not associated with the number of CD4+ cells or the viral load, but
      HAART reduced the prevalence of oral candidiasis. Overall, most patients harbored
      strains in vitro susceptible to fluconazole, however 10.8% of the yeasts were
      resistant to one or more azole antifungal agents and 29% were intermediate
      susceptible to them. On the contrary, 5-fluorocytosine was very active against
      all isolates tested, and amphotericin B was active against 97.9% of them.

PMID- 16107166
TI  - [Environmental distribution of Cryptococcus neoformans in the department of
      Cundinamarca-Colombia].
AB  - Cryptococcus neoformans is an opportunistic fungal pathogen that could cause
      infection in patients with immunodeficiency and healthy patients. The AIDS
      epidemic has shown the importance of studying the ecology and epidemiology of
      this fungus. The aim of this investigation was to determine if there was a
      relationship between the environmental distribution of the different varieties of
      C. neoformans and the climate zones in two transects located in department of
      Cundinamarca, in Colombia. For the isolation and identification of the yeast,
      conventional phenotypic methods were used and it was determined the population
      density (CFU/g of sample) and which was the variety of greater prevalence in each
      altitudinal rank. A total of 765 samples, from 26 municipalities were collected;
      of these 146 corresponded to pigeon droppings (Columba livia), 437 to Eucalyptus
      detritus (Eucalyptus camaldulensis and related species) and 182 to detritus of
      almond trees (Terminalia cattapa). C. neoformans was isolated from 46% of the
      studied municipalities, in both transects and the climate zones: warm, temperate
      and cold. The results indicated that the greater frequency of positive isolations
      came from the last climate zone (cold). The population density in pigeon
      excrements oscillated between 50 and 9.2 x 1,000,000, in eucalyptus between 500
      and 10 x 1,000,000 and in almond trees was 50 CFU/g. Of 100,000 positive
      isolations 31% were serotype A, 59% serotype B and 10% serotype C; 96% of the
      isolates grew to 37 degrees C and all showed capsule. In conclusion, C.
      neoformans prevails in the three habitats studied but it showed a predilection
      for the cold thermal floor; the population densities did not allow defining a
      standard pattern of occurrence.

PMID- 16107167
TI  - [Endophytic fungi in rose (Rosa hybrida) in Bogota, Colombia].
AB  - We have investigated the presence of endophytic fungi associated with rose plants
      (Rosa hybrida) in Colombia. Endophytic fungi were isolated from healthy leaves of
      ten ornamental roses plants from gardens cultured in malt extract, peptone, yeast
      extract agar plates (MPY). We sampled 560 leaves fragments, 56 per sample.
      Endophytic fungi comprised 92 isolates (16.4%); of these isolates, 41 were
      classified as sterile mycelium (without reproductive structures that allowed
      their identification), 31 isolates were identified to genus or to species, and 20
      isolates could not be identified at all. The identified endophytic fungi were as
      follow: Nigrospora oryzae, Aureobasidium spp, Acremonium spp. The fungi
      Nodulisporium sp, Gliocladium virens, Cladosporium sp, Alternaria sp, Phoma sp
      and Chaetomium globosum were represented by one isolate each. Since the
      endophytic fungi are known for their capacity to produce metabolites with
      biological activity, it is possible that the microorganisms found in this study
      have potential as antagonist of rose pathogens.

PMID- 16107168
TI  - [Direct fluorescent and indirect immunofluorescent assay in buffy coat for
      candidemia diagnosis in pediatric patients: a comparative study].
AB  - The diagnosis of candidemia by blood culture has poor sensitivity; therefore,
      immunossupresed patients and those with risk factors may receive empirical
      antifungal therapy, wich is potentially toxic. Fluorescent tests have been
      developed to obtain an early and more sensitive diagnosis than blood culture. The
      aim of this study was to compare indirect immunofluorescence vs direct calcofluor
      white fluorescence in buffy coat for candidemia diagnosis. Sensitivity,
      specificity, predictive values, of positive and negative samples were 60%, 86%,
      33%, 95% and 90%, 80%, 35%, 99%, for indirect immunofluorescence and calcofluor
      white, respectively.

PMID- 16107169
TI  - [In vitro susceptibility of fungal and yeast clinical isolates to itraconazole
      and voriconazole].
AB  - The interest on the in vitro susceptibility to itraconazole has recently
      increased due the availability of the intravenous formulation. In this study,
      comparative MICs of this antifungal with voriconazole were carried out in 62
      clinical isolates of filamentous fungi and 100 yeasts isolates using the NCCLS
      microbroth methods described in M38-A and M27-A2 documents. A MIC90 of 0.125
      micrograms per ml was observed for itraconazole and voriconazole against
      Aspergillus fumigatus. Higher susceptibility to itraconazole was found for the
      filamentous form of Sporotrhix schenckii (p = 0.001). Voriconazole was more
      effective against Scedosporium apiospermium while Scedosporium prolificans
      isolates were resistant to both azoles. Some isolates of Rhizopus stolonifer were
      susceptible to itraconazole and resistant to voriconazole, but without
      statistical significance. Susceptibility of nine species of Candida was similar
      for both triazoles used in this study. However, Candida glabrata was more
      susceptible to voriconazole. Some fluconazole-resistant Candida albicans isolates
      were susceptible to itraconazole and / or voriconazole. Cryptococcus neoformans
      was more susceptible to itraconazole than to voriconazole. Itraconazole and
      voriconazole showed very close in vitro activity against the tested fungal
      isolated, except against S. schenckii. In spite of this, there were some
      differences in susceptibility among isolates within the same fungal species.

PMID- 16107170
TI  - [In vitro antifungal activity of voriconazole against dermatophytes and
      superficial isolates of Scopulariopsis brevicaulis].
AB  - We have studied the in vitro antifungal activity of voriconazole, fluconazole and
      itraconazole against 252 clinical isolates of dermatophytes and Scopulariopsis
      brevicaulis by a standardized agar diffusion method (NeoSensitabs). Several
      important factors such as temperature (28 degrees C vs. 35 degrees C) and
      incubation time (2-10 days vs. 18-74 h) were adapted to dermatophytes and
      Scopulariopsis requirements. Voriconazole showed an excellent activity against
      most species of dermatophytes, higher than itraconazole and fluconazole. However,
      S. brevicaulis isolates were highly resistant to all azoles used in this study.
      Voriconazole might be an interesting antifungal alternative to refractory
      superficial mycoses.

PMID- 16107171
TI  - [Detection of extracellular protease in Mucor species].
AB  - The fungi are characterized by their abilities to produce and secrete enzymes to
      the external environment. The species of genus Mucor are a group of fungal
      microbes with important biotechnological potential, which are responsible for
      production of industrial enzymes. This work evaluated the ability of protease
      production in twelve species of genus Mucor. The strains were kept for 120 h
      under the incubation temperature of 28 degrees C on a shaker at 120 rpm. The
      detection of proteolytic activity was evaluated in all species, the higher
      activity was detected in Mucor racemosus Fres. f. chibinensis (Neophytova)
      Schipper.

PMID- 16107172
TI  - [Primary cutaneous mucormycosis. Report of a case in a HIV patient].
AB  - Primary cutaneous mucormycosis is an unusual mycotic infection associated to
      immunosupression. We present a 34 year-old woman with HIV infection with a
      necrotic primary mucormycosis of the skin associated to a venous catheter. She
      was treated with amphotericin B and surgical debridement.

PMID- 16107173
TI  - [Abdominal zygomycosis in a bitch due to Absidia corymbifera].
AB  - We report a case of abdominal zygomicosis in a Doberman bitch. Clinical signs
      consisted of urinary incontinence and hard abdominal masses detected by
      palpation. The masses were surgically removed by exploratory laparatomy and had a
      tumoral-like appearance. A granulomatous reaction containing coarse and non
      septate hyphae was the main histological finding. Direct microscopic examination
      revealed the presence of fungal structures. On Sabouraud honey agar the fungus
      developed fluffy, greyish white colonies that were identified as Absidia
      corymbifera on the basis of their macro and microscopic morphology.

PMID- 16107174
TI  - [Clinical cases in medical mycology. Case No. 16].

PMID- 16107175
TI  - Pathogenicity of environmental strains of Cryptococcus neoformans var neoformans
      in murine model.

PMID- 16107177
TI  - An overview of common medical comorbidities in patients with schizophrenia.

PMID- 16107178
TI  - Schizophrenia, antipsychotic drugs, and cardiovascular disease.
AB  - Since the early 1980s, concern within the psychiatric community about whether
      antipsychotics are associated with adverse cardiovascular events has grown. In
      the early 1990s, it became clear that mesoridazine could cause torsades de
      pointes. More recently, concern has focused on the propensity that some atypical
      antipsychotics have to prolong corrected QT (QTc) interval and whether this can
      result in torsades de pointes and sudden death. Unfortunately, it has been
      difficult to accurately determine what role, if any, that atypical antipsychotics
      may have in contributing to these events, in part because of the rarity of the
      events and the lack of a sound, predictable marker. The best currently available
      markers, QTc interval and binding to the rapid delayed rectifier potassium
      current, are imprecise and cannot be relied upon to accurately predict torsades
      de pointes. Current evidence suggests that although atypical antipsychotics may
      increase the QTc interval, prolongation does not result in torsades de pointes,
      as observed with many conventional antipsychotics. Among the marketed atypical
      drugs, there was considerable concern about QTc prolongation with ziprasidone,
      but currently available data do not support the occurrence of torsades de pointes
      with any of the available atypical antipsychotic drugs. However, identifying when
      QTc prolongation carries a risk of torsades de pointes remains a problem in
      developing new drugs. Psychiatric populations are at high risk for cardiovascular
      disease, and emerging data indicate that some atypical antipsychotics may be
      associated with cardiovascular adverse events unrelated to QT prolongation. Thus,
      it is prudent for the psychiatric community to be aware of psychiatric patients'
      baseline medical condition and their risk status for cardiovascular disease.

PMID- 16107179
TI  - Schizophrenia and comorbid metabolic disorders.
AB  - Comorbid metabolic disorders in patients with schizophrenia are underrecognized
      by many health care professionals and patients. That lack of awareness can
      contribute to serious morbidity and mortality in patients with schizophrenia.
      Patients with schizophrenia may be at greater risk for metabolic disorders such
      as insulin resistance, lipid abnormalities, and weight gain. In addition,
      although the use of atypical antipsychotics in the treatment of schizophrenia
      offers many positive benefits and may reduce some of the factors related to the
      morbidity and mortality of the disorder, these drugs appear to be associated with
      varying degrees of comorbid metabolic disorders, such as metabolic syndrome, and
      more serious consequences, such as cardiovascular disease. Recent consensus
      guidelines recommend that metabolic risks be considered when initiating therapy
      with atypical antipsychotics. Thus, baseline screening and routine monitoring of
      patient weight, fasting lipid profile, and fasting plasma glucose are essential.
      In addition, optimal treatment for patients with schizophrenia and comorbid
      metabolic disorders is best achieved when all parties involved with patient care
      (mental health and medical community, caregiver/family, and patient) communicate
      and work together. With proper awareness and cooperation on the part of the
      medical community, caregivers, and patients, the detrimental consequences that
      may result from the metabolic disorders addressed in this article can be at least
      partially offset.

PMID- 16107180
TI  - Schizophrenia and comorbid substance use disorder: effects of antipsychotics.
AB  - The rate of comorbid substance use disorder in patients with schizophrenia is 3
      times higher than that in the general population. Men with schizophrenia appear
      to be particularly vulnerable to substance use disorders. Substances commonly
      abused in patients with schizophrenia include alcohol, cannabis, and cocaine.
      Although the basis of comorbidity is unclear, a number of theories have been
      proposed, including the possibility of a deficiency in the dopamine-mediated
      mesocorticolimbic brain reward circuit. Data suggest that substance abuse may
      complicate and worsen the course of schizophrenia. Early intervention with
      appropriate pharmacotherapy may prove beneficial and potentially improve the long
      term course of the disorder. Conventional antipsychotics have not been overly
      useful in this patient population, but some atypical antipsychotics have been
      shown to reduce the use of alcohol, cannabis, cocaine, and tobacco in patients
      with schizophrenia. Further research is required, but early evidence suggests
      that at least some atypical antipsychotics may prove to be therapeutically
      effective in the treatment of patients with schizophrenia and comorbid substance
      use disorder.

PMID- 16107181
TI  - Schizophrenia and comorbid human immunodeficiency virus or hepatitis C virus.
AB  - Patients with schizophrenia are at significantly increased risk for infection
      with human immunodeficiency virus (HIV), hepatitis C virus, or both. Several
      factors underlie this increased risk, including substance abuse and high-risk
      sexual behavior. Although being sexually active tends to be less common among
      patients with schizophrenia than among nonpsychotic individuals, patients with
      schizophrenia who are sexually active are more likely than nonpsychotic
      individuals to engage in high-risk behavior. Many patients with schizophrenia
      have inadequate knowledge about the risks of HIV, but delivering factual
      information is not likely, by itself, to bring about behavioral changes that
      reduce the risk of exposure and transmission. Comorbidity of schizophrenia and
      life-threatening viral illnesses incurs a worse prognosis for both conditions.
      Nevertheless, effective pharmacotherapy exists, and antipsychotics and highly
      active antiretroviral treatments for HIV can be used together successfully. The
      clinical challenge is to encourage adherence to treatment and to coordinate the
      clinical services needed to address the diverse psychiatric and medical problems
      that coexist in this population.

PMID- 16107182
TI  - Neurologic comorbidities in schizophrenia.
AB  - Brain abnormalities have long been assumed to be involved in the pathophysiology
      of schizophrenia. Magnetic resonance imaging studies have identified numerous
      structural and functional imaging abnormalities, such as reduced brain volume,
      frontal lobe volume, and hippocampal volume, in patients with schizophrenia.
      Neurologic disorders, such as movement disorders, neurologic abnormalities, and
      cognitive deficits, are often seen years before the onset of schizophrenia. Many
      of these abnormalities may be predictive of the development of schizophrenia, but
      unfortunately, they are usually overlooked. In addition, treatment with
      antipsychotics may affect brain structure, further complicating the ability to
      detect changes due to the neuropathology of psychosis. This article reviews the
      structural and functional imaging abnormalities found in patients with
      schizophrenia and the neurologic disorders that commonly coexist with the
      disorder. The role that treatment with atypical antipsychotics may or may not
      have in contributing to neurologic abnormalities is also discussed. Through
      increased awareness of these abnormalities, the importance of obtaining a
      complete neurologic history and examination of patients with schizophrenia at the
      onset of their illness and before initiating pharmacotherapy will become evident.
      Such recognition may permit earlier identification and treatment of
      schizophrenia, thus potentially improving long-term outcome.

PMID- 16107183
TI  - Ratiometric singlet oxygen nano-optodes and their use for monitoring photodynamic
      therapy nanoplatforms.
AB  - Ratiometric photonic explorers for bioanalysis with biologically localized
      embedding (PEBBLE) nanoprobes have been developed for singlet oxygen, using
      organically modified silicate (ORMOSIL) nanoparticles as the matrix. A crucial
      aspect of these ratiometric singlet-oxygen fluorescent probes is their minute
      size. The ORMOSIL nanoparticles are prepared via a sol-gel-based process and the
      average diameter of the resultant particles is about 160 nm. These sensors
      incorporate the singlet-oxygen-sensitive 9,10-dimethyl anthracene as an indicator
      dye and a singlet-oxygen-insensitive dye, octaethylporphine, as a reference dye
      for ratiometric fluorescence-based analysis. We have found experimentally that
      these nanoprobes have much better sensitivity than does the conventional singlet
      oxygen-free dye probe, anthracene-9,10-dipropionic acid disodium salt. The much
      longer lifetime of singlet oxygen in the ORMOSIL matrix, compared to aqueous
      solutions, in addition to the relatively high singlet oxygen solubility because
      of the highly permeable structure and the hydrophobic nature of the outer shell
      of the ORMOSIL nanoparticles, results in an excellent overall response to singlet
      oxygen. These nanoprobes have been used to monitor the singlet oxygen produced by
      "dynamic nanoplatforms" that were developed for photodynamic therapy. The singlet
      oxygen nanoprobes could potentially be used to quantify the singlet oxygen
      produced by macrophages.

PMID- 16107185
TI  - Spectral properties of selected UV-blocking and UV-transmitting covering
      materials with application for production of high-value crops in high tunnels.
AB  - The spectral properties of selected UV-blocking and UV-transmitting covering
      materials were characterized by means of a UV-VIS spectroradiometer or a UV-VIS
      spectrometer to provide researchers and growers with guidelines for selecting
      suitable materials for use in studying the effects of ambient solar UV radiation
      on the production of tomatoes and other high-value crops in high tunnels. A
      survey was made of a wide range of plastic covering materials to identify
      commercially available products that had the desired characteristics of
      transmitting high levels of photosynthetically active radiation and of being
      stable under ambient solar UV radiation. The study was focused on evaluating
      films that either blocked or transmitted UV wavelengths below 380 nm to determine
      comparative growth, yield and market quality and to provide a tool for integrated
      pest management. Based on this survey, two contrasting covering materials of
      similar thickness (0.152 mm) and durability (4-year polyethylene), one a UV
      blocking film and the other a UV-transmitting film, were selected and used to
      cover two high tunnels at Beltsville, MD. Spectroradiometric measurements were
      made to determine comparative spectral irradiance in these two high tunnels
      covered with these materials and under ambient solar UV radiation. Comparative
      measurements were also made of selected glass and plastic materials that have
      been used in UV exclusion studies.

PMID- 16107187
TI  - Photophysics and photochemistry of nalidixic acid.
AB  - The photophysics and photochemistry of nalidixic acid (NA) were studied as
      function of pH and solvent properties. The ground state of NA exhibits different
      protonated forms in the range of pH 1.8-10.0. Fluorescence studies showed that
      the same species exist at the lowest singlet excited state. Absorption
      experiments were carried out with NA and with the methylated analog of nalidixic
      acid (MNE) in different organic solvents and water pH 3, where the main species
      corresponds to that protonated at the carboxylic group. These studies and the DFT
      calculation of torsional potential energy profiles suggest that the most stable
      conformation of the NA in nonprotic solvents corresponds to a closed structure
      caused by the existence of intramolecular hydrogen bond. Absorption and
      fluorescence spectra were studied in sulfuric acid solution. The pK value (Ho 
      1.0) found in these conditions was attributed to the protonation of the 4' keto
      oxygen atom of the heterocyclic ring. Theoretical calculations (DFT/B3LYP/6
      311G*) of the energies of the different monoprotonated forms of the NA and Fukui
      indexes (f(x)-) showed that the species with the proton attached to 4' keto
      oxygen atom is the most stable of all the cationic forms. MNE and enoxacin also
      showed the protonation of the 4' keto oxygen atom with similar pK values. The
      photodecomposition of NA is dependent on the medium properties. Faster
      decomposition rates were obtained in strong acid solution. In nonprotic solvents,
      a very slow decomposition rate was observed.

PMID- 16107186
TI  - Dissection of the inflammatory bowel disease transcriptome using genome-wide cDNA
      microarrays.
AB  - BACKGROUND: The differential pathophysiologic mechanisms that trigger and
      maintain the two forms of inflammatory bowel disease (IBD), Crohn disease (CD),
      and ulcerative colitis (UC) are only partially understood. cDNA microarrays can
      be used to decipher gene regulation events at a genome-wide level and to identify
      novel unknown genes that might be involved in perpetuating inflammatory disease
      progression. METHODS AND FINDINGS: High-density cDNA microarrays representing
      33,792 UniGene clusters were prepared. Biopsies were taken from the sigmoid colon
      of normal controls (n = 11), CD patients (n = 10) and UC patients (n = 10). 33P
      radiolabeled cDNA from purified poly(A)+ RNA extracted from biopsies (unpooled)
      was hybridized to the arrays. We identified 500 and 272 transcripts
      differentially regulated in CD and UC, respectively. Interesting hits were
      independently verified by real-time PCR in a second sample of 100 individuals,
      and immunohistochemistry was used for exemplary localization. The main findings
      point to novel molecules important in abnormal immune regulation and the highly
      disturbed cell biology of colonic epithelial cells in IBD pathogenesis, e.g.,
      CYLD (cylindromatosis, turban tumor syndrome) and CDH11 (cadherin 11, type 2). By
      the nature of the array setup, many of the genes identified were to our knowledge
      previously uncharacterized, and prediction of the putative function of a
      subsection of these genes indicate that some could be involved in early events in
      disease pathophysiology. CONCLUSION: A comprehensive set of candidate genes not
      previously associated with IBD was revealed, which underlines the polygenic and
      complex nature of the disease. It points out substantial differences in
      pathophysiology between CD and UC. The multiple unknown genes identified may
      stimulate new research in the fields of barrier mechanisms and cell signalling in
      the context of IBD, and ultimately new therapeutic approaches.

PMID- 16107188
TI  - Spectroscopic and photochemical properties of the lichen compound lobaric acid.
AB  - Lichens synthesize and accumulate photoprotective compounds against possible
      damage induced by UV radiation in the photobiont. A biological model has been
      recently formulated that allows the use of lichens to evaluate changes at
      different UV radiation levels. The thermodynamics, photophysical and
      photochemical properties of lobaric acid were studied in acetonitrile, ethanol
      and Brij 35(3%) micelles at different pH values. Also the sun protector factor
      (SPF) was determined by in vitro methods. Lobaric acid was extracted from
      Stereoculon alpinum Laur. and characterized by means of standard procedures.
      Solutions were irradiated in oxygen and under nitrogen conditions with a UV
      medium pressure lamp. Lobaric acid absorbs at 287, 303 nm, and no fluorescence
      emission was observed. The maximum value of the molar extinction coefficient
      (5479.6 M(-1) cm(-1)) was obtained in Brij 35 at pH 12. Solubility is pH
      dependant and is highest in Brij 35 at pH 12 (4.45 x 10(-4) M). Photoconsumption
      quantum yields ranged between 10(-4) and 10(-5) in aerobic and anaerobic
      experimental conditions. Lobaric acid SPF was very low (0.5) compared with
      homosalate (4.0), (reference solar filter). Two pKa values, 5.05 (carboxylic acid
      group deprotonation) and 9.75 (phenolic OH deprotonation), were determined.

PMID- 16107190
TI  - Community-acquired methicillin-resistant Staphylococcus aureus: time to address
      the problem.

PMID- 16107193
TI  - Posaconazole: clinical pharmacology and potential for management of fungal
      infections.
AB  - Posaconazole is a novel lipophilic antifungal triazole that inhibits cytochrome
      P450-dependent 14-alpha demethylase in the biosynthetic pathway of ergosterol.
      Inhibition of this enzyme leads to an accumulation of toxic 14-alpha
      methylsterols and a depletion of ergosterol, resulting in a perturbation of the
      function of the fungal cell membrane and blockage of cell growth and division. In
      vitro, posaconazole has potent and broad-spectrum activity against opportunistic,
      endemic and dermatophytic fungi. This activity extends to organisms that are
      often refractory to existing triazoles, amphotericin B or echinocandins, such as
      Candida glabrata, Candida krusei, Aspergillus terreus, Fusarium spp. and the
      Zygomycetes. A large variety of animal models of invasive fungal infections have
      provided consistent evidence of efficacy against these organisms in vivo, both in
      normal and immunocompromised animals. Posaconazole is available as an oral
      suspension and optimal exposure is achieved when the drug is administered in two
      to four divided doses along with food or a nutritional supplement. The compound
      has a large volume of distribution, in the order of 5 l/kg, and a half-life of
      approximately 20 h. Posaconazole is not metabolized to a significant extent
      through the cytochrome P450 enzyme system and is primarily excreted in an
      unchanged form in the feces. Although it is inhibitory, cytochrome P3A4 has no
      effect on 1A2, 2C8, 2C9, 2D6 and 2E1 isoenzymes, and therefore, a limited
      spectrum of drug-drug interactions can be expected. Pharmacokinetic studies in
      special populations revealed no necessity for dosage adjustment based on
      differences in age, gender, race, renal or hepatic function. Posaconazole has
      demonstrated strong antifungal efficacy in Phase II and III clinical trials in
      immunocompromised patients with oropharyngeal and esophageal candidiasis.
      Posaconazole also showed promising efficacy as salvage therapy in a large Phase
      II study including 330 patients with invasive fungal infections intolerant to or
      refractory to standard therapies. Posaconazole appears to be well tolerated in a
      manner comparable with that of fluconazole and it is currently under regulatory
      review in the USA and Europe for the treatment of refractory invasive fungal
      infections. This drug profile reviews the preclinical and clinical pharmacology
      of posaconazole and its potential role for prevention and treatment of invasive
      fungal infections.

PMID- 16107194
TI  - Telbivudine: an upcoming agent for chronic hepatitis B.
AB  - Telbivudine, the prototype member of beta-L-2 -deoxynucleosides, has proven to be
      safe in in vitro animal and human studies. Telbivudine given for 4 weeks resulted
      in an 8-log reduction of woodchuck hepatitis virus DNA, and a 3.8-log reduction
      of hepatitis B virus DNA in human. After 52 weeks of telbivudine treatment there
      was an approximate 6-log reduction of hepatitis B virus DNA levels, hepatitis B
      virus DNA became undetectable by PCR assay in 61% of patients. Its antiviral
      efficacy is significantly better than lamivudine. The probability of tyrosine
      methionine-aspartate-aspartate mutations at 52 weeks of telbivudine therapy is
      low, although still occurring in 4.5% of patients. After 96 weeks of therapy, the
      proportion of patients with undetectable hepatitis B virus DNA by PCR assay
      increased to 71%, but genotypic resistance also increased to 18.2%, with only
      4.5% showing alanine aminotransferase flares. Telbivudine is probably one of the
      most potent antiviral agents for hepatitis B virus that will become available in
      the near future.

PMID- 16107195
TI  - Peginterferon-alpha2a (40 kDa) (Pegasys) for hepatitis B.
AB  - Chronic hepatitis B virus is a serious and life threatening disease afflicting
      350 million people worldwide, despite the availability of effective vaccines.
      Thus far, current monotherapy with conventional interferon-alpha, lamivudine and
      adefovir dipivoxil remains unsatisfactory. In addition, the use of conventional
      interferon-alpha needs to be administered subcutaneously three-times weekly and
      is associated with frequent adverse events. Although nucleoside/nucleotide
      analogs such as lamivudine and adefovir dipivoxil are well tolerated and can
      normalize serum alanine aminotransaminase rapidly, 1-year therapy with either
      lamivudine or adefovir dipivoxil results in low hepatitis B e antigen
      seroconversion rates. In hepatitis B e antigen-negative patients, most would
      relapse after lamivudine has been discontinued. Peginterferon-alpha2a, an
      immunomodulatory agent, is a new drug that has just completed Phase III clinical
      trials for the treatment of both hepatitis B e antigen-positive and -negative
      chronic hepatitis B virus infection. The advantage of peginterferon-alpha2a in
      achieving sustained virologic response over nucleoside/nucleotide analogs is
      particularly obvious in the hepatitis B e antigen-negative group. In both
      studies, sustained off-treatment response is superior to the use of monotherapy
      with lamivudine, and concomitant use of lamivudine and pegnterferon-alpha2a does
      not have advantages over the use of peginterferon-alpha2a alone. These recent
      data put peginterferon-alpha2a as the antihepatitis B virus therapy of choice,
      especially in young and motivated patients with chronic hepatitis B virus
      infection. However, despite the superiority of peginterferon-alpha2a over
      currently licensed nucleoside/nucleotide analogs, more research needs to be
      conducted in order to find the most optimal treatment regimen in our fight
      against chronic hepatitis B virus infection.

PMID- 16107196
TI  - Anti-MRSA agents: under investigation, in the exploratory phase and clinically
      available.
AB  - Staphylococcal infections are difficult to treat due to the rapid emergence of
      methicillin-resistant staphylococci and, unfortunately, vancomycin-intermediate
      or -resistant staphylococci. Numerous alternative treatments are urgently
      required. In this special report, intensive research of new molecules is
      highlighted--in known antibacterial families and new medicinal chemical entities.

PMID- 16107197
TI  - Current use of anti-infectives in dermatology.
AB  - Dermatologic diseases encompass a broad category of pathologic situations.
      Infection remains a significant aspect of the pathology faced in patient
      encounters, and it is natural to expect that anti-infectives play a major element
      in the armamentarium utilized by dermatologists. Aside from the treatment of the
      classic bacterial and fungal infections, there are now new uses for antiviral
      agents to help suppress recurrent disease, such as herpes simplex. There is also
      the novel approach of using anti-infectives, or agents that have been thought to
      have antimicrobial activity, to treat inflammatory diseases. This review
      describes anti-infectives, beginning with common antibiotics used to treat
      bacterial infections. The discussion will then cover the current use of
      antivirals. Finally, the description of antifungals will be separated, starting
      with the oral agents and ending with the topical antimycotics. The use of anti
      infectives in tropical dermatology has been purposefully left out, and perhaps
      should be the subject of a separate review. Cutaneous bacterial infections
      consist chiefly of those microorganisms that colonize the skin, such as species
      of staphylococcus and streptococcus. Propionibacterium acnes and certain other
      anaerobes can be involved in folliculitis, pyodermas and in chronic conditions
      such as hidradenitis suppurativa.

PMID- 16107198
TI  - Management of severe bacterial infections.
AB  - Defining the severity of an infection can play a central role for a correct
      therapeutic choice, avoiding inadequate antimicrobial treatments. Severe
      bacterial infections are, in fact, characterized by high morbidity and mortality
      rates so that the appropriateness of therapy can have a profound clinical impact.
      Indeed, initial inappropriate empirical therapies, and the further need to modify
      them, substantially increase the mortality risk. Several strategies have been
      suggested to improve the clinical outcome of patients affected by severe
      bacterial infections, such as the use of guidelines, use of antibiotics in
      combination, de-escalation therapy, cycling therapy and the use of infectious
      disease specialist consultation. A closer collaboration between the medical staff
      in the wards and infectious disease specialists can possibly bridge the gap
      between different strategies and individual needs of the patient, thereby
      improving the decision-making process.

PMID- 16107199
TI  - Therapy of infections caused by dematiaceous fungi.
AB  - Dematiaceous fungi are responsible for a wide variety of clinical syndromes, from
      local infections due to trauma, to disseminated infection in immunocompromised
      patients. These fungi are unique owing to the presence of melanin in their cell
      walls, which imparts the characteristic dark color to their spores and hyphae.
      Melanin may also be a virulence factor in these fungi. Therapy depends upon the
      clinical syndrome. Local infection may be cured with excision alone, while
      systemic disease is often refractory to therapy. Azoles such as itraconazole and
      voriconazole have the most consistent in vitro activity, although newer agents
      may also play a role in therapy in the future.

PMID- 16107200
TI  - Invasive pulmonary aspergillosis.
AB  - In susceptible patients, invasive aspergillosis has a high incidence and a
      mortality of up to 80%. The diagnosis of this condition is difficult, especially
      in the early stages of the disease and, as a consequence, antifungal therapy,
      despite its expense and toxicity, is often initiated empirically. Until recently,
      there were very few effective antifungal agents for established invasive
      aspergillosis, but the introduction of two new drugs, voriconazole and
      caspofungin, has increased the treatment options. These newer antifungal
      therapies, combined with improved early diagnosis due to the introduction of
      newer microbiologic techniques, offer the hope that there will be a significant
      improvement in the substantial morbidity and mortality associated with invasive
      aspergillosis over the next 5 years.

PMID- 16107201
TI  - Management of infections by the human polyomavirus JC: past, present and future.
AB  - Progressive multifocal leukoencephalopathy is a fatal demyelinating disease
      caused by infection of oligodendrocytes by the human polyomavirus known as JC
      virus. Over the past 10 years, the disease has been documented almost exclusively
      in AIDS patients, who constitute a rapidly growing population of immunosuppressed
      individuals. More recently, progressive multifocal leukoencephalopathy has also
      been described in patients undergoing solid organ or cell transplant, as a result
      of immunosuppressive therapy to avoid graft rejection. Although there are several
      reports of successful treatment of progressive multifocal leukoencephalopathy,
      large-scale prospective trials have been few, and with mixed results. As more is
      discovered about the biology of JC virus infection and advances are made in
      targeted parenchymal delivery of therapeutic agents, there is hope for the
      development of an effective therapy for progressive multifocal
      leukoencephalopathy.

PMID- 16107202
TI  - Coxsackievirus-induced myocarditis: new trends in treatment.
AB  - Myocarditis is a common inflammatory heart disease in children and young adults
      that may result in chronically dilated cardiomyopathy. Coxsackievirus B3 is the
      major etiologic agent of this disease. Current treatments for patients with viral
      myocarditis are almost entirely supportive. In recent years, some promising
      therapeutic candidates have emerged, including novel treatments and improvements
      of existing drugs. Among these are molecules that specially target virus entry,
      such as pleconaril, WIN 54954 and CAR-Fc; nucleic acid-based antiviral agents
      that inhibit viral translation and/or transcription, such as antisense
      oligodeoxynucleotide and short interfering RNA; and immunomodulatory agents that
      augment the host-protective immune responses to effectively clear viruses from
      target tissues, including interferons and immunoglobulins. In addition, certain
      new antiviral strategies, still in the early stages, include modulation of signal
      transduction pathways responsible for viral replication using enzyme inhibitors,
      which have revealed potential therapeutic targets for viral myocarditis. Finally,
      the progress in cellular cardiomyoplasty for end-stage therapy, in particular the
      preliminary clinical trials, is also discussed with respect to its potential
      future application.

PMID- 16107203
TI  - Intrauterine infection with parvovirus B19 and CMV: implications in early and
      late gestation fetal demise.
AB  - In utero viral infections have been associated with an adverse pregnancy outcome
      and may have a causative role in the unexplained fetal death file. Parvovirus B19
      and cytomegalovirus are among the most common pathogens implicated in fetal loss
      cases. Parvovirus B19 has been reported to account for cases of spontaneous
      abortions, intrauterine fetal death and nonimmune hydrops fetalis, whereas
      cytomegalovirus accounts for nonimmune hydrops fetalis, intrauterine growth
      retardation and congenital anomalies. This review aims to summarize the current
      literature in an attempt to underline the need for routine screening, close
      follow-up and prevention. A better understanding of the pathogenetic mechanisms
      of viral infections during the crucial time of organogenesis, along with early
      detection, may contribute to the reduction in stillbirth rate.

PMID- 16107204
TI  - Main adult herpes virus infections of the CNS.
AB  - Herpes viruses are widely involved in human infectious diseases, and some are
      life threatening, such as CNS infections. These manifestations vary according to
      the type of virus involved and the immune status of the patient. This article
      will review the clinical manifestations (encephalitis, myelitis, meningitis and
      postinfectious encephalomyelitis), the diagnostic strategies and the presently
      used drugs (acyclovir, valacyclovir, ganciclovir, valgancyclovir, foscarnet and
      cidofovir). The review will also discuss drugs that are currently in the pipeline
      and that could be used in the future.

PMID- 16107205
TI  - Physical and biochemical properties of mammalian DNase X proteins: non-AUG
      translation initiation of porcine and bovine mRNAs for DNase X.
AB  - DNase X is the first human DNase protein identified as being homologous with
      DNase I. In the present study we describe the isolation of several mammalian
      DNase X cDNAs and the molecular characterization of their coding proteins. A
      sequence comparison reveals some conserved characteristics: all the mammalian
      DNase X proteins have an N-terminal signal peptide, a potential N-linked
      glycosylation site and a C-terminal hydrophobic domain. Human DNase X,
      ectopically expressed in HeLa S3 cells, is located in the ER (endoplasmic
      reticulum) and is modified by an N-linked glycosylation at Asn-243. Gene
      expression analyses show that the high expression level in muscular tissues, a
      known feature of human DNASE X, is also observed in mouse DNase X. Interestingly,
      the translation of porcine and bovine DNase X proteins occurs in the absence of
      an in-frame AUG initiation codon. We show that their mRNAs utilize a conserved
      CUG triplet for translation initiation.

PMID- 16107206
TI  - Molecular cloning and characterization of PLC-eta2.
AB  - PLC (phospholipase C) isoenzymes catalyse the conversion of PtdIns(4,5)P2 into
      the Ca2+-mobilizing second messenger, Ins(1,4,5)P3, and the protein kinase C
      activating second messenger, diacylglycerol. With the goal of identifying
      additional mammalian PLC isoenzymes, we screened the NCBI non-redundant database
      using a BLAST algorithm for novel sequences with homology with the conserved PLC
      catalytic core. Two unique sequences corresponding to two unknown PLC isoenzymes
      were identified, and one of these, designated PLC-eta2, was cloned and
      characterized. Most of the coding sequence of PLC-eta2 was constructed from two
      ESTs (expressed sequence tags), which included an overlapping sequence that was
      confirmed by multiple ESTs and mRNAs. 5'-RACE (rapid amplification of cDNA ends)
      also identified an upstream exon not deduced from available EST or mRNA
      sequences. Sequence analysis of PLC-eta2 revealed the canonical domains of a PLC
      isoenzyme with an additional long C-terminus that contains a class II PDZ-binding
      motif. Genomic analyses indicated that PLC-eta2 is encoded by 23 exons. RT-PCR
      (reverse transcriptase-PCR) analyses illustrated expression of PLC-eta2 in human
      retina and kidney, as well as in mouse brain, eye and lung. RT-PCR with exon
      specific primers also revealed tissue-specific expression of four splice variants
      in mouse that represent alternative use of sequences in exons 21, 22 and 23. PLC
      eta2-specific antisera recognized one of these splice variants as an approx. 155
      kDa species when expressed in COS-7 cells; PLC-eta2 natively expressed in 1321N1
      human astrocytoma cells also migrated as an approx. 155 kDa species. PLC activity
      was observed in vitro and in vivo for three different constructs of PLC-eta2,
      each containing possible alternatively spliced first exons. Co-expression of PLC
      eta2 with Gbeta1gamma2 dimers of heterotrimeric G-proteins resulted in marked
      stimulation of inositol lipid hydrolysis. Thus PLC-eta2 may in part function
      downstream of G-protein-coupled receptors.

PMID- 16107207
TI  - Trafficking defects of the Southeast Asian ovalocytosis deletion mutant of anion
      exchanger 1 membrane proteins.
AB  - Human AE1 (anion exchanger 1) is a membrane glycoprotein found in erythrocytes
      and as a truncated form (kAE1) in the BLM (basolateral membrane) of a
      intercalated cells of the distal nephron, where they carry out electroneutral
      chloride/bicarbonate exchange. SAO (Southeast Asian ovalocytosis) is a dominant
      inherited haematological condition arising from deletion of Ala400-Ala408 in AE1,
      resulting in a misfolded and transport-inactive protein present in the ovalocyte
      membrane. Heterozygotes with SAO are able to acidify their urine, without
      symptoms of dRTA (distal renal tubular acidosis) that can be associated with
      mutations in kAE1. We examined the effect of the SAO deletion on stability and
      trafficking of AE1 and kAE1 in transfected HEK-293 (human embryonic kidney) cells
      and kAE1 in MDCK (Madin-Darby canine kidney) epithelial cells. In HEK-293 cells,
      expression levels and stabilities of SAO proteins were significantly reduced, and
      no mutant protein was detected at the cell surface. The intracellular retention
      of AE1 SAO in transfected HEK-293 cells suggests that erythroid-specific factors
      lacking in HEK-293 cells may be required for cell-surface expression. Although
      misfolded, SAO proteins could form heterodimers with the normal proteins, as well
      as homodimers. In MDCK cells, kAE1 was localized to the cell surface or the BLM
      after polarization, while kAE1 SAO was retained intracellularly. When kAE1 SAO
      was co-expressed with kAE1 in MDCK cells, kAE1 SAO was largely retained
      intracellularly; however, it also co-localized with kAE1 at the cell surface. We
      propose that, in the kidney of heterozygous SAO patients, dimers of kAE1 and
      heterodimers of kAE1 SAO and kAE1 traffic to the BLM of a-intercalated cells,
      while homodimers of kAE1 SAO are retained in the endoplasmic reticulum and are
      rapidly degraded. This results in sufficient cell-surface expression of kAE1 to
      maintain adequate bicarbonate reabsorption and proton secretion without dRTA.

PMID- 16107208
TI  - The type III inositol 1,4,5-trisphosphate receptor is phosphorylated by cAMP
      dependent protein kinase at three sites.
AB  - IP3 (inositol 1,4,5-trisphosphate) receptors form tetrameric, IP3-gated Ca2+
      channels in endoplasmic reticulum membranes, and are substrates for several
      kinases, including PKA (cAMP-dependent protein kinase). Activation of PKA has
      been reported to either enhance or inhibit type III IP3 receptor Ca2+-channel
      activity, but, as yet, the sites of phosphorylation remain unknown. Here, we
      reveal that PKA phosphorylates the type III IP3 receptor at Ser916, Ser934 and
      Ser1832, and that, intriguingly, each site is located close to a putative surface
      exposed peptide loop. Furthermore, we demonstrate that Ser934 is considerably
      more susceptible to PKA-dependent phoshorylation than either Ser916 or Ser1832.
      These findings define the sites at which the type III IP3 receptor is
      phosphorylated by PKA, and provide the basis for exploring the functional
      consequences of this regulatory event.

PMID- 16107209
TI  - Does contrast echocardiography induce increases in markers of myocardial
      necrosis, inflammation and oxidative stress suggesting myocardial injury?
AB  - BACKGROUND: Contrast echocardiography is a precise tool for the non-invasive
      assessment of myocardial function and perfusion. Side effects of contrast
      echocardiography resulting from contrast-agent induced myocardial micro-lesions
      have been found in animals. The goal of this study is to measure markers of
      myocardial necrosis, inflammation and oxidative stress in humans to evaluate
      potential side-effects of contrast echocardiography. METHODS: 20 patients who
      underwent contrast echocardiography with Optison as the contrast medium were
      investigated. To evaluate myocardial micro-necrosis, inflammation and oxidative
      stress, cardiac troponin I (cTnI), tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-6, -8 and thiobarbituric acid reactive substances (TBARS) were
      measured at baseline and at 2, 4, 8 and 24 hours after contrast echocardiography.
      RESULTS: At baseline, 50% of the patients had cTnI and TBARS values outside the
      reference range. TNF-alpha, IL-6, IL-8 levels were within the reference range.
      Patients with cTnI above the RR clustered to significantly higher levels of TNF
      alpha and IL-6. After contrast echocardiography, no statistically significant
      increase of cTnI, cytokines and TBARS was found. However, for nearly 50% of the
      patients, the intra-individual cTnI kinetics crossed the critical difference
      (threefold of methodical variation) which indicates a marker increase. This was
      neither predicted by the baseline levels of the cytokines nor the markers of
      oxidative stress. CONCLUSION: There are no clinically relevant increases in serum
      markers for micro-necrosis, inflammation and oxidative stress in humans after
      contrast echocardiography. Future studies have to address whether cTnI increase
      in some patients represent a subset with increased risk for side effects after
      contrast echocardiography.

PMID- 16107210
TI  - Dual activation of pathways regulated by steroid receptors and peptide growth
      factors in primary prostate cancer revealed by Factor Analysis of microarray
      data.
AB  - BACKGROUND: We use an approach based on Factor Analysis to analyze datasets
      generated for transcriptional profiling. The method groups samples into
      biologically relevant categories, and enables the identification of genes and
      pathways most significantly associated to each phenotypic group, while allowing
      for the participation of a given gene in more than one cluster. Genes assigned to
      each cluster are used for the detection of pathways predominantly activated in
      that cluster by finding statistically significant associated GO terms. We tested
      the approach with a published dataset of microarray experiments in yeast. Upon
      validation with the yeast dataset, we applied the technique to a prostate cancer
      dataset. RESULTS: Two major pathways are shown to be activated in organ-confined,
      non-metastatic prostate cancer: those regulated by the androgen receptor and by
      receptor tyrosine kinases. A number of gene markers (HER3, IQGAP2 and POR1)
      highlighted by the software and related to the later pathway have been validated
      experimentally a posteriori on independent samples. CONCLUSION: Using a new
      microarray analysis tool followed by a posteriori experimental validation of the
      results, we have confirmed several putative markers of malignancy associated with
      peptide growth factor signalling in prostate cancer and revealed others, most
      notably ERRB3 (HER3). Our study suggest that, in primary prostate cancer, HER3,
      together or not with HER4, rather than in receptor complexes involving HER2,
      could play an important role in the biology of these tumors. These results
      provide new evidence for the role of receptor tyrosine kinases in the
      establishment and progression of prostate cancer.

PMID- 16107211
TI  - Molecular cloning and characterization of a nuclear androgen receptor activated
      by 11-ketotestosterone.
AB  - Although 11-ketotestosterone is a potent androgen and induces male secondary sex
      characteristics in many teleosts, androgen receptors with high binding affinity
      for 11-ketotestosterone or preferential activation by 11-ketotestosterone have
      not been identified. So, the mechanism by which 11-ketotestosterone exhibits such
      high potency remains unclear. Recently we cloned the cDNA of an 11
      ketotestosterone regulated protein, spiggin, from three-spined stickleback renal
      tissue. As spiggin is the only identified gene product regulated by 11
      ketotestosterone, the stickleback kidney is ideal for determination of the
      mechanism of 11-ketotestosterone gene regulation. A single androgen receptor gene
      with two splicing variants, belonging to the androgen receptor-beta subfamily was
      cloned from stickleback kidney. A high affinity, saturable, single class of
      androgen specific binding sites, with the characteristics of an androgen
      receptor, was identified in renal cytosolic and nuclear fractions. Measurement of
      ligand binding moieties in the cytosolic and nuclear fractions as well as to the
      recombinant receptor revealed lower affinity for 11-ketotestosterone than for
      dihydrotestosterone. Treatment with different androgens did not up-regulate
      androgen receptor mRNA level or increase receptor abundance, suggesting that auto
      regulation is not involved in differential ligand activation. However, comparison
      of the trans-activation potential of the stickleback androgen receptor with the
      human androgen receptor, in both human HepG2 cells and zebrafish ZFL cells,
      revealed preferential activation by 11-ketotestosterone of the stickleback
      receptor, but not of the human receptor. These findings demonstrate the presence
      of a receptor preferentially activated by 11-ketotestosterone in the three-spined
      stickleback, so far the only one known in any animal.

PMID- 16107212
TI  - Development of ESTs from chickpea roots and their use in diversity analysis of
      the Cicer genus.
AB  - BACKGROUND: Chickpea is a major crop in many drier regions of the world where it
      is an important protein-rich food and an increasingly valuable traded commodity.
      The wild annual Cicer species are known to possess unique sources of resistance
      to pests and diseases, and tolerance to environmental stresses. However, there
      has been limited utilization of these wild species by chickpea breeding programs
      due to interspecific crossing barriers and deleterious linkage drag. Molecular
      genetic diversity analysis may help predict which accessions are most likely to
      produce fertile progeny when crossed with chickpea cultivars. While, trait
      markers may provide an effective tool for breaking linkage drag. Although SSR
      markers are the assay of choice for marker-assisted selection of specific traits
      in conventional breeding populations, they may not provide reliable estimates of
      interspecific diversity, and may lose selective power in backcross programs based
      on interspecific introgressions. Thus, we have pursued the development of gene
      based markers to resolve these problems and to provide candidate gene markers for
      QTL mapping of important agronomic traits. RESULTS: An EST library was
      constructed after subtractive suppressive hybridization (SSH) of root tissue from
      two very closely related chickpea genotypes (Cicer arietinum). A total of 106 EST
      based markers were designed from 477 sequences with functional annotations and
      these were tested on C. arietinum. Forty-four EST markers were polymorphic when
      screened across nine Cicer species (including the cultigen). Parsimony and PCoA
      analysis of the resultant EST-marker dataset indicated that most accessions
      cluster in accordance with the previously defined classification of primary (C.
      arietinum, C. echinospermum and C. reticulatum), secondary (C. pinnatifidum, C.
      bijugum and C. judaicum), and tertiary (C. yamashitae, C. chrossanicum and C.
      cuneatum) gene-pools. A large proportion of EST alleles (45%) were only present
      in one or two of the accessions tested whilst the others were represented in up
      to twelve of the accessions tested. CONCLUSION: Gene-based markers have proven to
      be effective tools for diversity analysis in Cicer and EST diversity analysis may
      be useful in identifying promising candidates for interspecific hybridization
      programs. The EST markers generated in this study have detected high levels of
      polymorphism amongst both common and rare alleles. This suggests that they would
      be useful for allele-mining of germplasm collections for identification of
      candidate accessions in the search for new sources of resistance to pests /
      diseases, and tolerance to abiotic stresses.

PMID- 16107213
TI  - BMP4 signaling is involved in the generation of inner ear sensory epithelia.
AB  - BACKGROUND: The robust expression of BMP4 in the incipient sensory organs of the
      inner ear suggests possible roles for this signaling protein during induction and
      development of auditory and vestibular sensory epithelia. Homozygous BMP4-/-
      animals die before the inner ear's sensory organs develop, which precludes
      determining the role of BMP4 in these organs with simple gene knockout
      experiments. RESULTS: Here we use a chicken otocyst culture system to perform
      quantitative studies on the development of inner ear cell types and show that
      hair cell and supporting cell generation is remarkably reduced when BMP signaling
      is blocked, either with its antagonist noggin or by using soluble BMP receptors.
      Conversely, we observed an increase in the number of hair cells when cultured
      otocysts were treated with exogenous BMP4. BMP4 treatment additionally prompted
      down-regulation of Pax-2 protein in proliferating sensory epithelial progenitors,
      leading to reduced progenitor cell proliferation. CONCLUSION: Our results
      implicate BMP4 in two events during chicken inner ear sensory epithelium
      formation: first, in inducing the switch from proliferative sensory epithelium
      progenitors to differentiating epithelial cells and secondly, in promoting the
      differentiation of hair cells within the developing sensory epithelia.

PMID- 16107214
TI  - Quasispecies theory in the context of population genetics.
AB  - BACKGROUND: A number of recent papers have cast doubt on the applicability of the
      quasispecies concept to virus evolution, and have argued that population genetics
      is a more appropriate framework to describe virus evolution than quasispecies
      theory. RESULTS: I review the pertinent literature, and demonstrate for a number
      of cases that the quasispecies concept is equivalent to the concept of mutation
      selection balance developed in population genetics, and that there is no
      disagreement between the population genetics of haploid, asexually-replicating
      organisms and quasispecies theory. CONCLUSION: Since quasispecies theory and
      mutation-selection balance are two sides of the same medal, the discussion about
      which is more appropriate to describe virus evolution is moot. In future work on
      virus evolution, we would do good to focus on the important questions, such as
      whether we can develop accurate, quantitative models of virus evolution, and to
      leave aside discussions about the relative merits of perfectly equivalent
      concepts.

PMID- 16107215
TI  - Functional, radiological and biological markers of alveolitis and infections of
      the lower respiratory tract in patients with systemic sclerosis.
AB  - BACKGROUND: A progressive lung disease and a worse survival have been observed in
      patients with systemic sclerosis and alveolitis. The objective of this study was
      to define the functional, radiological and biological markers of alveolitis in
      SSc patients. METHODS: 100 SSc patients (76 with limited and 24 with diffuse
      disease) underwent a multistep assessment of cardiopulmonary system: pulmonary
      function tests (PFTs) every 6-12 months, echocardiography, high resolution
      computed tomography (HRCT) and bronchoalveolar lavage (BAL), if clinically
      advisable. Alveolar and interstitial scores on HRCT and IL-6 plasma levels were
      also assessed as lung disease activity indices. RESULTS: 90 SSc patients with
      abnormal PFTs and 3 with signs and/or symptoms of lung involvement and normal
      PFTs underwent HRCT and echocardiography. HRCT revealed evidence of fibrosis in
      87 (93.5%) patients, with 55 (59.1%) showing both ground glass attenuation and
      fibrosis. In 42 patients who had exhibited ground glass on HRCT and consented to
      undergo BAL, 16 (38.1%) revealed alveolitis. 12 (75%) of these patients had
      restrictive lung disease (p < 0.0001) and presented diffuse skin involvement (p =
      0.0009). IL-6 plasma levels were higher in patients with alveolitis than in
      patients without (p = 0.041). On logistic regression model the best independent
      predictors of alveolitis were diffuse skin involvement (OR(95%CIs):12.80(2.54
      64.37)) and skin score > 14 (OR(95%CIs):7.03(1.40-34.33)). The alveolar score
      showed a significant correlation with IL-6 plasma levels (r = 0.36, p = 0.001)
      and with the skin score (r = 0.33, p = 0.001). Cultures of BAL fluid resulted
      positive in 10 (23.8%) of the 42 patients that underwent BAL and after one year a
      deterioration in PFTs occurred in 8 (80%) of these patients (p = 0.01). Pulmonary
      artery systolic pressure > or = 40 mmHg was found in 6 (37.5%) patients with
      alveolitis. CONCLUSION: We found alveolitis only in 38.1% of the patients who had
      exhibited ground glass on HRCT and then underwent BAL, probably because the
      concomitant fibrosis influenced results. A diffuse skin involvement and a
      restrictive pattern on PFTs together with ground glass on HRCT were judged
      possible markers of alveolitis, a BAL examination being indicated as the next
      step. Nevertheless BAL would be necessary to detect any infections of the lower
      respiratory tract that may cause further deterioration in lung function.

PMID- 16107216
TI  - Fatigue resistance of rat extraocular muscles does not depend on creatine kinase
      activity.
AB  - BACKGROUND: Creatine kinase (CK) links phosphocreatine, an energy storage system,
      to cellular ATPases. CK activity serves as a temporal and spatial buffer for ATP
      content, particularly in fast-twitch skeletal muscles. The extraocular muscles
      are notoriously fast and active, suggesting the need for efficient ATP buffering.
      This study tested the hypotheses that (1) CK isoform expression and activity in
      rat extraocular muscles would be higher, and (2) the resistance of these muscles
      to fatigue would depend on CK activity. RESULTS: We found that mRNA and protein
      levels for cytosolic and mitochondrial CK isoforms were lower in the extraocular
      muscles than in extensor digitorum longus (EDL). Total CK activity was
      correspondingly decreased in the extraocular muscles. Moreover, cytoskeletal
      components of the sarcomeric M line, where a fraction of CK activity is found,
      were downregulated in the extraocular muscles as was shown by immunocytochemistry
      and western blotting. CK inhibition significantly accelerated the development of
      fatigue in EDL muscle bundles, but had no major effect on the extraocular
      muscles. Searching for alternative ATP buffers that could compensate for the
      relative lack of CK in extraocular muscles, we determined that mRNAs for two
      adenylate kinase (AK) isoforms were expressed at higher levels in these muscles.
      Total AK activity was similar in EDL and extraocular muscles. CONCLUSION: These
      data indicate that the characteristic fatigue resistance of the extraocular
      muscles does not depend on CK activity.

PMID- 16107217
TI  - Evidence of HIV exposure and transient seroreactivity in archived HIV-negative
      severe hemophiliac sera.
AB  - BACKGROUND: Approximately 25% of hemophiliacs that were frequently exposed to
      blood clotting factor concentrates (CFCs) contaminated with human
      immunodeficiency virus (HIV) are presently HIV seronegative. In this study, we
      sought to determine if some of these individuals were at any time transiently HIV
      seropositive. In the early to mid-1980s the majority of severe hemophilia
      patients were exposed to CFCs contaminated with HIV. Although many of these
      hemophiliacs became HIV-positive, a small percentage did not become infected. To
      determine if some of these individuals successfully resisted viral infection, we
      attempted to document the presence of transient HIV reactive antibodies in
      archived plasma samples (1980-1992) from currently HIV-negative severe
      hemophiliacs who had a high probability of repeated exposure to HIV contaminated
      CFC. Archived plasma samples were retrospectively tested using an FDA approved
      HIV-1Ab HIV-1/HIV-2 (rDNA) enzyme immunoassay (EIA) and a HIV-1 Western blot
      assay (Wb), neither of which were commercially available until the late 1980s,
      which was after many of these samples had been drawn. RESULTS: We found that
      during the high risk years of exposure to HIV contaminated CFC (1980-1987), low
      levels of plasma antibodies reactive with HIV proteins were detectable in 87%
      (13/15) of the haemophiliacs tested. None of these individuals are presently
      positive for HIV proviral DNA as assessed by polymerase chain reaction (PCR).
      CONCLUSION: Our data suggest that some severe hemophiliacs with heavy exposure to
      infectious HIV contaminated CFC had only transient low-level humoral immune
      responses reactive with HIV antigens yet remained HIV-negative and apparently
      uninfected. Our data supports the possibility of HIV exposure without sustained
      infection and the existence of HIV-natural resistance in some individuals.

PMID- 16107218
TI  - G0/G1 arrest and apoptosis induced by SARS-CoV 3b protein in transfected cells.
AB  - Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), cause of the life
      threatening atypical pneumonia, infects many organs, such as lung, liver and
      immune organ, and induces parenchyma cells apoptosis and necrosis. The genome of
      SARS-CoV, not closely related to any of the previously characterized coronavirus,
      encodes replicase and four major structural proteins and a number of non
      structural proteins. Published studies suggest that some non-structural proteins
      may play important roles in the replication, virulence and pathogenesis of
      viruses. Among the potential SARS-CoV non-structural proteins, 3b protein (ORF4)
      is predicted encoding 154 amino acids, lacking significant similarities to any
      known proteins. Till now, there is no report about the function of 3b protein. In
      this study, 3b gene was linked with the EGFP tag at the C- terminus. Through cell
      cycle analysis, it was found that over-expression of 3b-EGFP protein in Vero, 293
      and COS-7 cells could induce cell cycle arrest at G0/G1 phase, and that
      especially in COS-7 cells, expression of 3b-EGFP was able to induce the increase
      of sub-G1 phase from 24 h after transfection, which was most obvious at 48 h. The
      apoptosis induction of 3b fusion protein in COS-7 cells was further confirmed by
      double cell labeling with 7-AAD and Annexin V, the function of 3b protein
      inducing cell G0/G1 arrest and apoptosis may provide a new insight for further
      study on the mechanism of SARS pathogenesis.

PMID- 16107219
TI  - Protective action of a hexane crude extract of Pterodon emarginatus fruits
      against oxidative and nitrosative stress induced by acute exercise in rats.
AB  - BACKGROUND: The aim of the present work was to evaluate the effect of a hexane
      crude extract (HCE) of Pterodon emarginatus on the oxidative and nitrosative
      stress induced in skeletal muscle, liver and brain of acutely exercised rats.
      METHODS: Adult male rats were subjected to acute exercise by standardized
      contractions of the tibialis anterior (TA) muscle (100 Hz, 15 min) and treated
      orally with the HCE (once or three times with a fixed dose of 498 mg/kg), before
      and after acute exercise. Serum creatine kinase activity was determined by a
      kinetic method and macrophage infiltration by histological analyses of TA muscle.
      Lipid peroxidation was measured as malondialdehyde (MDA) levels. Nitric oxide
      production was evaluated by measuring nitrite formation, using Griess reagent,
      and nitrotyrosine was assessed by western blotting. RESULTS: Serum creatine
      kinase activities in the controls (111 U/L) increased 1 h after acute exercise
      (443 U/L). Acute exercise also increased the infiltration of macrophages into TA
      muscle; lipid peroxidation levels in TA muscle (967%), liver (55.5%) and brain
      (108.9%), as well as the nitrite levels by 90.5%, 30.7% and 60%, respectively.
      The pattern of nitrotyrosine formation was also affected by acute exercise.
      Treatment with HCE decreased macrophage infiltration, lipid peroxidation, nitrite
      production and nitrotyrosine levels to control values. CONCLUSION: Acute exercise
      induced by functional electrical stimulation in rats resulted in increase in
      lipid peroxidation, nitrite and nitrotyrosine levels in brain, liver and skeletal
      muscle. The exercise protocol, that involved eccentric muscle contraction, also
      caused some muscle trauma, associated with over-exertion, leading to
      inflammation. The extract of P. emarginatus abolished most of these oxidative
      processes, thus confirming the high antioxidant activity of this oil which
      infusions are used in folk medicine against inflammatory processes.

PMID- 16107220
TI  - Reverse transcriptional profiling: non-correspondence of transcript level
      variation and proximal promoter polymorphism.
AB  - BACKGROUND: Variation in gene expression between two Drosophila melanogaster
      strains, as revealed by transcriptional profiling, seldom corresponded to
      variation in proximal promoter sequence for 34 genes analyzed. Two sets of
      protein-coding genes were selected from pre-existing microarray data: (1) those
      whose expression varied significantly and reproducibly between strains, and (2)
      those whose transcript levels did not vary. Only genes whose regulation of
      expression was uncharacterized were chosen. At least one kB of the proximal
      promoters of 15-19 genes in each set was sequenced and compared between strains
      (Oregon R and Russian 2b). RESULTS: Of the many promoter polymorphisms, 89.6%
      were SNPs and 10.4% were indels, including homopolymer tracts, microsatellite
      repeats, and putative transposable element footprints. More than half of the SNPs
      were changes within a nucleotide class. Hypothetically, genes differing in
      expression between the two strains should have more proximal promoter
      polymorphisms than those whose expression is similar. The number, frequency, and
      type of polymorphism, however, were the same in both sets of genes. In fact, the
      promoters of six genes with significantly different mRNA expression were
      identical in sequence. CONCLUSION: For these genes, sequences external to the
      proximal promoter, such as enhancers or in trans, must play a greater role than
      the proximal promoter in transcriptomic variation between D. melanogaster
      strains.

PMID- 16107221
TI  - Quantitative assessment of harmonic power doppler myocardial perfusion imaging
      with intravenous Levovist in patients with myocardial infarction: comparison with
      myocardial viability evaluated by coronary flow reserve and coronary flow pattern
      of infarct-related artery.
AB  - BACKGROUND: Myocardial contrast echocardiography and coronary flow velocity
      pattern with a rapid diastolic deceleration time after percutaneous coronary
      intervention has been reported to be useful in assessing microvascular damage in
      patients with acute myocardial infarction. AIM: To evaluate myocardial contrast
      echocardiography with harmonic power Doppler imaging, coronary flow velocity
      reserve and coronary artery flow pattern in predicting functional recovery by
      using transthoracic echocardiography. METHODS: Thirty patients with anterior
      acute myocardial infarction underwent myocardial contrast echocardiography at
      rest and during hyperemia and were quantitatively analyzed by the peak color
      pixel intensity ratio of the risk area to the control area (PIR). Coronary flow
      pattern was measured using transthoracic echocardiography in the distal portion
      of left anterior descending artery within 24 hours after recanalization and we
      assessed deceleration time of diastolic flow velocity. Coronary flow velocity
      reserve was calculated two weeks after acute myocardial infarction. Left
      ventricular end-diastolic volumes and ejection fraction by angiography were
      computed. RESULTS: Pts were divided into 2 groups according to the deceleration
      time of coronary artery flow pattern (Group A; 20 pts with deceleration time > or
      = 600 msec, Group B; 10 pts with deceleration time < 600 msec). In acute phase,
      there were no significant differences in left ventricular end-diastolic volume
      and ejection fraction (Left ventricular end-diastolic volume 112 +/- 33 vs. 146
      +/- 38 ml, ejection fraction 50 +/- 7 vs. 45 +/- 9 %; group A vs. B). However,
      left ventricular end-diastolic volume in Group B was significantly larger than
      that in Group A (192 +/- 39 vs. 114 +/- 30 ml, p < 0.01), and ejection fraction
      in Group B was significantly lower than that in Group A (39 +/- 9 vs. 52 +/- 7%,
      p < 0.01) at 6 months. PIR and coronary flow velocity reserve of Group A were
      higher than Group B (PIR, at rest: 0.668 +/- 0.178 vs. 0.248 +/- 0.015, p <
      0.0001: during hyperemia 0.725 +/- 0.194 vs. 0.295 +/- 0.107, p < 0.0001;
      coronary flow velocity reserve, 2.60 +/- 0.80 vs. 1.31 +/- 0.29, p = 0.0002,
      respectively). CONCLUSION: The preserved microvasculature detecting by myocardial
      contrast echocardiography and coronary flow velocity reserve is related to
      functional recovery after acute myocardial infarction.

PMID- 16107222
TI  - Procalcitonin-guided antibiotic use versus a standard approach for acute
      respiratory tract infections in primary care: study protocol for a randomised
      controlled trial and baseline characteristics of participating general
      practitioners [ISRCTN73182671].
AB  - BACKGROUND: Acute respiratory tract infections (ARTI) are among the most frequent
      reasons for consultations in primary care. Although predominantly viral in
      origin, ARTI often lead to the prescription of antibiotics for ambulatory
      patients, mainly because it is difficult to distinguish between viral and
      bacterial infections. Unnecessary antibiotic use, however, is associated with
      increased drug expenditure, side effects and antibiotic resistance. A novel
      approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum
      levels of ProCT are elevated in bacterial infections but remain lower in viral
      infections and inflammatory diseases. The aim of this trial is to compare a ProCT
      guided antibiotic therapy with a standard approach based on evidence-based
      guidelines for patients with ARTI in primary care. METHODS/DESIGN: This is a
      randomised controlled trial in primary care with an open intervention. Adult
      patients judged by their general practitioner (GP) to need antibiotics for ARTI
      are randomised in equal numbers either to standard antibiotic therapy or to ProCT
      guided antibiotic therapy. Patients are followed-up after 1 week by their GP and
      after 2 and 4 weeks by phone interviews carried out by medical students blinded
      to the goal of the trial. Exclusion criteria for patients are antibiotic use in
      the previous 28 days, psychiatric disorders or inability to give written informed
      consent, not being fluent in German, severe immunosuppression, intravenous drug
      use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation.
      The primary endpoint is days with restrictions from ARTI within 14 days after
      randomisation. Secondary outcomes are antibiotic use in terms of antibiotic
      prescription rate and duration of antibiotic treatment in days, days off work and
      days with side-effects from medication within 14 days, and relapse rate from the
      infection within 28 days after randomisation. DISCUSSION: We aim to include 600
      patients from 50 general practices in the Northwest of Switzerland. Data from the
      registry of the Swiss Medical Association suggests that our recruited GPs are
      representative of all eligible GPs with respect to age, proportion of female
      physicians, specialisation, years of postgraduate training and years in private
      practice.

PMID- 16107224
TI  - Closed chamber globe stabilization and needle capsulorhexis using irrigation hand
      piece of bimanual irrigation and aspiration system.
AB  - BACKGROUND: The prerequisites for a good capsulorhexis include a deep, well
      maintained anterior chamber, globe stabilization and globe manipulation. This
      helps to achieve a capsulorhexis of optimal size, shape and obtain the best
      possible position for a red glow under retroillumination. We report the use of
      irrigation handpiece of bimanual irrigation aspiration system to stabilize the
      globe, maintain a deep anterior chamber and manipulate the globe to a position of
      optimal red reflex during needle capsulorhexis in phacoemulsification. METHODS:
      Two side ports are made with 20 G MVR 'V' lance knife (Alcon, USA). The
      irrigation handpiece with irrigation on is introduced into the anterior chamber
      through one side port and the 26-G cystitome (made from 26-G needle) is
      introduced through the other. The capsolurhexis is completed with the needle.
      RESULTS: Needle capsulorhexis with this technique was used in 30 cases of
      uncomplicated immature senile cataracts. 10 cases were done under peribulbar
      anaesthesia and 20 under topical anaesthesia. A complete capsulorhexis was
      achieved in all cases. CONCLUSION: The irrigating handpiece maintains deep
      anterior chamber, stabilizes the globe, facilitates pupillary dilatation, and
      helps in maintaining the eye in the position with optimal red reflex during
      needle capsulorhexis. This technique is a safe and effective way to perform
      needle capsulorhexis.

PMID- 16107225
TI  - Biologic insights from the sequenced genome of Entamoeba histolytica.

PMID- 16107223
TI  - Retroviral superinfection resistance.
AB  - The retroviral phenomenon of superinfection resistance (SIR) defines an
      interference mechanism that is established after primary infection, preventing
      the infected cell from being superinfected by a similar type of virus. This
      review describes our present understanding of the underlying mechanisms of SIR
      established by three characteristic retroviruses: Murine Leukaemia Virus (MuLV),
      Foamy Virus (FV), and Human Immunodeficiency Virus (HIV). In addition, SIR is
      discussed with respect to HIV superinfection of humans. MuLV resistant mice
      exhibit two genetic resistance traits related to SIR. The cellular Fv4 gene
      expresses an Env related protein that establishes resistance against MuLV
      infection. Another mouse gene (Fv1) mediates MuLV resistance by expression of a
      sequence that is distantly related to Gag and that blocks the viral infection
      after the reverse transcription step. FVs induce two distinct mechanisms of
      superinfection resistance. First, expression of the Env protein results in SIR,
      probably by occupancy of the cellular receptors for FV entry. Second, an increase
      in the concentration of the viral Bet (Between-env-and-LTR-1-and-2) protein
      reduces proviral FV gene expression by inhibition of the transcriptional
      activator protein Tas (Transactivator of spumaviruses). In contrast to SIR in FV
      and MuLV infection, the underlying mechanism of SIR in HIV-infected cells is
      poorly understood. CD4 receptor down-modulation, a major characteristic of HIV
      infected cells, has been proposed to be the main mechanism of SIR against HIV,
      but data have been contradictory. Several recent studies report the occurrence of
      HIV superinfection in humans; an event associated with the generation of
      recombinant HIV strains and possibly with increased disease progression. The role
      of SIR in protecting patients from HIV superinfection has not been studied so
      far. The phenomenon of SIR may also be important in the protection of primates
      that are vaccinated with live attenuated simian immunodeficiency virus (SIV)
      against pathogenic SIV variants. As primate models of SIV infection closely
      resemble HIV infection, a better knowledge of SIR-induced mechanisms could
      contribute to the development of an HIV vaccine or other antiviral strategies.

PMID- 16107226
TI  - Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: emerging
      insights for vascular integrity.

PMID- 16107227
TI  - Lower tidal volume ventilation and plasma cytokine markers of inflammation in
      patients with acute lung injury.

PMID- 16107228
TI  - Epidemiology of sepsis: recent advances.
AB  - Sepsis, as defined by an expert consensus definition, is the development of the
      systemic inflammatory response syndrome in the presence of infection. Using this
      clinically applicable definition, several studies have evaluated the epidemiology
      of sepsis over the past decade. The current incidence of sepsis is at least 240
      patients per 100,000 people in the United States population, whereas for severe
      sepsis it is between 51 and 95 patients per 100,000 people. The incidence rate
      for sepsis has been increasing over the past two decades, driving an increase in
      the number of deaths despite a decline in case-fatality rates. Sepsis is the
      tenth leading cause of death in the United States and accounts for more than 17
      billion dollars in direct healthcare expenditures.

PMID- 16107229
TI  - The multiple organ dysfunction syndrome and late-phase mortality in sepsis.
AB  - Sepsis is a devastating and common syndrome characterized by systemic
      inflammation. Sepsis accounts for considerable morbidity and mortality among
      intensive care unit patients. Although the inflammatory response generated by the
      immune system represents the body's attempt to clear invading pathogens, it is
      the failure to modulate this response that leads to dysregulated inflammation and
      the injury of healthy tissue. A great deal of research has characterized many of
      the early events and mediators that lead to systemic inflammation and sepsis.
      However, substantially less is known about the pathogenesis of the late phase of
      sepsis, which accounts for the vast majority of sepsis-related mortality (ie, the
      dysfunction and subsequent failure of the major parenchymal organs).

PMID- 16107230
TI  - Ventilatory strategies in patients with sepsis and respiratory failure.
AB  - Patients with sepsis may require mechanical ventilation due to the acute
      respiratory distress syndrome (ARDS). It has become increasingly accepted that
      mechanical ventilation can contribute to lung injury in these patients. The
      modern concept of ventilator-induced lung injury is described in the context of
      alveolar over-distention (volutrauma), alveolar de-recruitment (atelectrauma),
      and biochemical injury and inflammation to the lung parenchyma (biotrauma). To
      avoid over-distention lung injury, the tidal volume should be set at 6 mL/kg
      predicted body weight and plateau pressure should be limited to 30 cm H2O. This
      has been shown to afford a survival benefit. Although setting positive end
      expiratory pressure (PEEP) to zero is likely harmful during mechanical
      ventilation of patients with ARDS, evidence is lacking for a survival benefit if
      a high PEEP level is set compared with a modest level of PEEP. Although
      adjunctive measures such as recruitment maneuvers, prone position, and inhaled
      nitric oxide may improve oxygenation, evidence is lacking that these measures
      improve survival.

PMID- 16107231
TI  - Complement-induced Impairment of the Innate Immune System During Sepsis.
AB  - The complement system is an integral part of innate immunity and is chiefly
      responsible for controlling bacterial infections, especially those involving gram
      negative organisms. To accomplish this task, serum proteins engage in a series
      of enzymatic cascades. The cleaved proteins assemble pores on membranous
      structures, which lead to cell lysis. During this process, powerful inflammatory
      mediators are produced, including the anaphylatoxins, C5a, C3a, and the membrane
      attack complex (MAC). Under systemic inflammatory conditions, an overactive
      complement system may compromise the effectiveness of innate immunity. We review
      the detrimental effects that are caused by uncontrolled complement activation
      during sepsis.

PMID- 16107232
TI  - New Antimicrobial Agents Active against Staphylococcus aureus.

PMID- 16107233
TI  - Skin manifestations of herpesvirus infections.
AB  - Currently there are eight human herpesviruses identified that cause disease in
      both adults and children. Although the manifestations of disease differ with each
      herpesvirus, cutaneous presentations are common among almost all of them. These
      skin manifestations may be visually similar among several of these viruses,
      occasionally making it challenging to diagnose the patient's illness. Laboratory
      diagnostic testing is commercially available for most of these viruses. Because
      many herpesvirus infections are self-limiting in immunocompetent hosts, patients
      require only supportive care. Effective antiviral therapy is available for the
      more severe cases of infection caused by herpes simplex virus (HSV), varicella
      zoster virus (VZV), or cytomegalovirus (CMV). Healthcare practitioners should
      become familiar with the different cutaneous manifestations these viruses may
      exhibit.

PMID- 16107234
TI  - Musculoskeletal infection imaging: past, present, and future.
AB  - Imaging plays a key role in the evaluation of patients with known or suspected
      musculoskeletal infection. Although conventional radiograph still remains as the
      initial imaging approach, it has low sensitivity and specificity in the setting
      of acute infection. Magnetic resonance is highly sensitive for the detection of
      acute osteomyelitis and septic arthritis. Computed tomography is usually reserved
      for guided interventional procedures (eg, aspiration or drainage) and for
      evaluation of sinus tracts in chronic infections. Ultrasound is useful for fluid
      detection in joints and soft tissues but limited in bone assessment. Nuclear
      medicine, with the different radiotracers currently available, is highly
      sensitive for the diagnosis of acute osteomyelitis. Newer radiotracers are being
      developed that promise high sensitivity and specificity for the detection of
      these pathologies.

PMID- 16107235
TI  - Ectoparasitic infestations.
AB  - Ectoparasitic infestations are highly prevalent in resource-poor populations
      throughout the world and are associated with considerable morbidity. Reliable
      data on the epidemiology, immunology, and therapy of ectoparasitic infestations
      and on the biology of the parasites remain scarce. The control of parasitic skin
      diseases, such as scabies, pediculosis, tungiasis, myiasis, and cutaneous larva
      migrans in endemic areas remains a challenge. Using appropriate study designs, it
      is imperative to increase further the knowledge on the various aspects of the
      parasites and the infestations they cause.

PMID- 16107236
TI  - Impact of community-associated, methicillin-resistant Staphylococcus aureus on
      management of the skin and soft tissue infections in children.
AB  - Skin and soft tissue infections (SSTIs) are common illnesses that have a
      significant impact on health care management. Community-associated, methicillin
      resistant Staphylococcus aureus (CA-MRSA) infections have been documented among
      healthy individuals without predisposing risk factors. The appearance and spread
      of CA-MRSA represent a new challenge in pediatric medicine and have important
      clinical implications for therapy of infections caused by S. aureus. This article
      provides a review of recent changes in the epidemiology of CA-MRSA, pathogenic
      potential, and therapeutic considerations in the management of SSTIs in children.

PMID- 16107237
TI  - Progress and Emerging Challenges in Preventing Mother-to-Child Transmission.
AB  - There is a widening gulf between the effectiveness of interventions for
      preventing mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa and
      other regions of the world. Compared with long-course, triple antiretroviral
      regimens used in Brazil, Europe, and the United States, most countries in sub
      Saharan Africa use a less effective regimen consisting of single-dose nevirapine
      (NVP). Furthermore, the documentation of unacceptable levels of resistance
      following this regimen makes it prudent to review current PMTCT strategies. Not
      only is it necessary to review the use of single-dose NVP for PMTCT, but efforts
      to minimize breast milk transmission of HIV should be enhanced. This review
      summarizes the programmatic and evidence-based reasons for adopting a
      standardized approach to long-course, triple-drug MTCT prophylaxis in sub-Saharan
      Africa. Antiretroviral treatment programs in resource-constrained settings have
      achieved similar levels of effectiveness as high-income countries, despite
      adopting standardized approaches to antiretroviral treatment. Similarly, in
      resource-constrained settings with adequate infrastructure and programmatic
      capacity, use of standardized, long-course, triple-drug regimens for MTCT
      prevention are likely to achieve levels of effectiveness seen in Brazil, Europe,
      and the United States.

PMID- 16107238
TI  - HIV in Adolescents.
AB  - Adolescence is a time of dramatic physical, emotional, cognitive, and social
      change that brings new vulnerabilities. Youth represent half of all new HIV
      infections in the United States and the rest of the world. The number of newly
      infected adolescents who acquire the disease behaviorally and the number of
      perinatally infected children surviving into adolescence have both contributed to
      this growth. This article reviews the most recent epidemiology of HIV/AIDS in
      adolescents, gives guidance on clinical practice, including medical and
      psychosocial care, and examines prevention issues, including counseling and
      testing, which are needed to make programs effective for youth.

PMID- 16107239
TI  - Promising systemic therapy for renal cell carcinoma.
AB  - In the United States, advanced kidney cancer accounts for over 12,000 deaths each
      year. Immunotherapy with either interferon or interleukin-2 (IL-2) has been the
      standard of care for over two decades. High-dose IL-2 can apparently cure 10% to
      15% of patients treated, but due to the required inpatient care and the attendant
      toxicities, it is only administered to less than 1,000 patients per year in the
      United States (Chiron, personal communication). Interferon is a less active agent
      than IL-2 but it has still been shown to be superior to therapy with either
      megesterol or vinblastine. Interferon typically results in very few long-term
      responses and is given to most patients with metastatic kidney cancer. Median
      survival after interferon therapy is dependent on risk group but is typically 12
      to 15 months. Thus, new therapies are urgently needed in this refractory disease.
      Novel compounds currently being tested in clinical trials are showing promise in
      advanced kidney cancer. The molecular targets of these drugs include interfering
      with the vascular endothelial growth factor receptors or the raf kinase pathway,
      angiogenesis inhibition, and antimicrotubule agents. A review of the preclinical
      and early clinical development of some of these novel compounds will be
      discussed.

PMID- 16107240
TI  - Management of patients with low-stage nonseminomatous germ cell testicular
      cancer.
AB  - Management options for patients with clinical stage (CS) I nonseminomatous germ
      cell testicular cancer (NSGCT) include surveillance, retroperitoneal lymph node
      dissection (RPLND), or two cycles of bleomycin-etoposide-cisplatin (BEP x 2)
      chemotherapy. The optimal management of these patients is controversial, as cure
      rates of 97% or greater are reported with each of these treatment modalities.
      Patients without evidence of lymphovascular invasion, a predominant component of
      embryonal carcinoma, or advanced pathologic (p) T stage (pT 2 or greater) are at
      low risk for occult metastases and are optimal candidates for surveillance.
      Compliance with diagnostic testing and imaging is essential for a successful
      surveillance strategy to detect and treat metastases at an early stage. For
      patients who are not candidates for surveillance, RPLND offers several advantages
      over chemotherapy. RPLND alone is curative in 50% to 80% of CS I patients with
      pathologic stage (PS) II, and an estimated 75% of CS I patients avoid
      chemotherapy (as adjuvant therapy or for treatment of relapse). Virtually all
      patients are cured following two cycles of adjuvant chemotherapy for PS II
      disease, which is reserved for patients with high-volume (PN2-3) retroperitoneal
      disease. The poor outcome of patients with late retroperitoneal recurrence from
      unresected, chemorefractory germ cell testicular cancer indicates that RPLND is a
      vital component to the long-term cure of patients with NSGCT. Approximately 20%
      to 30% of patients with PS II disease have retroperitoneal teratoma (which is
      chemoresistant), and an estimated 5% of PS II patients have chemoresistant viable
      cancer following BEP x 2 as primary therapy. When RPLND is omitted, these
      patients are at risk for late recurrence with potentially lethal consequences.
      Patients who relapse after RPLND are "chemotherapy-naive" and cured in virtually
      all cases with good-risk chemotherapy regimens. When nerve-sparing techniques are
      employed to preserve ejaculation, RPLND is also associated with a more favorable
      long-term toxicity profile compared with chemotherapy. In the absence of
      conclusive evidence from a randomized trial, we believe RPLND is the treatment of
      choice for patients with CS I NSGCT who are not candidates for surveillance, as
      it offers the greatest likelihood of long-term cure with considerably less
      morbidity than primary chemotherapy.

PMID- 16107241
TI  - Thermal-based treatment options for localized prostate cancer.
AB  - It seems clear that thermal-based therapies of prostate cancer have the potential
      to completely eradicate the prostate gland. Technical modifications continue to
      improve our ability to use these modalities more effectively, which can be seen
      in the ever decreasing morbidity from damage to adjacent structures. These
      treatments offer potential major advantages over surgery and radiation-based
      treatment modalities.

PMID- 16107242
TI  - Prostate brachytherapy for localized prostate cancer.
AB  - After skin cancer, prostate cancer (CaP) is the most common cancer diagnosed in
      men. As a result of screening with prostate-specific antigen, CaP is being caught
      earlier than it was in the past. This has led to an increase in cure rates across
      all treatment modalities. There are no firm, reproducible data that demonstrate
      the superiority of one modality over another. The expectations for cure should be
      approximately 90% for low-risk patients and approximately 80% for intermediate
      risk patients, regardless of treatment modality. The toxicity of available
      treatment modalities discriminates among them. All modalities have acute toxicity
      of similar severity; however, prostate brachytherapy (PI) has the least amount of
      long-term toxicity when compared with external beam radiotherapy and radical
      prostatectomy. Therefore, a patient who is confronted with the diagnosis of CaP
      is counseled to choose among the modalities based on the toxicity rather than the
      efficacy of the treatment options available. Adopting this evidence-based
      algorithm has led to the increased application of PI.

PMID- 16107243
TI  - Advances in the treatment of neuroendocrine tumors.
AB  - Gastrointestinal neuroendocrine tumors are characterized by generally slow growth
      rates and the ability to secrete a variety of hormones and biogenic amines. For
      patients with localized disease, surgical resection alone is often curative;
      however, patients with metastatic disease often present a therapeutic challenge.
      Although somatostatin analogs are highly effective in controlling symptoms of
      hormonal secretion, they are rarely associated with tumor regression. Selected
      patients with hepatic metastases may benefit from surgical debulking,
      embolization, or other ablative therapies. The clinical benefit associated with
      the administration of systemic agents such as alpha interferon or cytotoxic
      chemotherapy is less clear, and the widespread use of such regimens has been
      limited by their relatively modest antitumor activity as well as by concerns
      regarding their potential toxicity. The highly vascular nature of neuroendocrine
      tumors has led to interest in angiogenesis inhibition as a potentially novel
      treatment strategy. In addition, several small molecule tyrosine kinase
      inhibitors are currently being evaluated in a Phase II setting. The naturally
      indolent growth of neuroendocrine tumors presents a challenge in interpreting
      efficacy endpoints from small Phase II studies. Larger, randomized trials, along
      with the evaluation of surrogate endpoints of biologic activity, may be necessary
      to establish the potential clinical benefit of these novel agents.

PMID- 16107244
TI  - Anti-angiogenic strategies in gastrointestinal malignancies.
AB  - Advances in our understanding of the mechanisms underlying tumor progression
      suggest that angiogenesis plays a key role in gastrointestinal malignancies.
      Vascular endothelial growth factor (VEGF) has emerged as an important therapeutic
      target, and a variety of strategies to inhibit VEGF are under investigation. The
      approval of bevacizumab for use in patients with previously untreated metastatic
      colorectal cancer was based on clinical data suggesting that VEGF is a valid
      therapeutic target in this disease. As the data mature from ongoing trials, the
      role of angiogenesis inhibitors in the treatment of colon cancer and other
      gastrointestinal malignancies will be more clearly defined. Additional
      information is needed to identify the diseases and stages most likely to benefit
      from anti-angiogenic agents and the optimal sequences and therapeutic
      combinations that should be studied.

PMID- 16107245
TI  - Management of hepatocellular cancer.
AB  - The nearly ubiquitous association of hepatocellular cancer (HCC) with underlying
      liver dysfunction portends a dismal prognosis. At the time of presentation with
      HCC, many patients have advanced cirrhosis that precludes effective therapy.
      Important prognostic factors include characteristics of the tumor (size,
      location, involvement of major blood vessels) and the functional state of the
      liver (quantified by synthetic function and portal hypertension). Localized
      tumors in a noncirrhotic liver may be treated successfully with surgical
      resection. In the setting of mild to moderate cirrhosis, localized therapy such
      as radiofrequency ablation, percutaneous ethanol ablation, chemoembolization, or
      Yttrium 90 microsphere infusion may be options, depending on the liver reserve
      and resources available. In the setting of advanced cirrhosis, treatment of the
      tumor may exacerbate liver decompensation, resulting in a shortened survival. In
      all of these instances, regardless of the therapy pursued, the underlying field
      defect with malignant potential remains in place. Liver transplantation has been
      employed to resolve both life-threatening problems, but it is fraught with many
      barriers. Appropriate patient selection and the use of adjuvant therapies are
      being pursued to improve the outcome of transplantation for HCC. Patients may
      have limited therapy options if they have poor performance status, are not
      surgical candidates, have a tumor that extends into the main portal vein, or have
      metastases to distant lymph nodes or organs. Chemotherapy is of marginal
      efficacy. Emerging therapies exploiting molecular targets are being explored with
      some promise.

PMID- 16107246
TI  - Management strategies for patients with hereditary pancreatic cancer.
AB  - It is likely that hereditary factors play a role in 17% or more of pancreatic
      cancers. Ten percent of patients have a familial history that causes disease.
      Another 7% have a history of apparently "sporadic" pancreatic cancer patients
      carry a genetic mutation that causes the disease. Kindreds, with two or more
      family members who have been diagnosed with pancreatic cancer and who are first
      degree relatives, are considered to have familial pancreatic cancer (FPC). The
      inheritance pattern for FPC is usually autosomal dominant; however, the
      penetrance (whether a gene carrier gets the disease) is variable. The lifetime
      cancer risk for a gene-carrying individual from a FPC kindred can range from 5%
      to 100%, depending upon the gene inherited and environment-gene interactions.
      Smoking is the chief environmental risk factor that influences penetrance of
      pancreatic cancer in these kindreds. Smoking increases the risk of cancer by more
      than threefold and decreases the age of onset by approximately 10 years. The
      precursor lesion to pancreatic cancer is pancreatic intraepithelial neoplasia
      (PanIN), which is graded I to III depending upon the severity of the neoplastic
      change. Surveillance for the early detection of cancer or intraepithelial
      neoplasia is possible in high-risk individuals and should be performed in centers
      with expertise. Endoscopic ultrasound and endoscopic retrograde
      cholangiopancreatography can help identify those patients who have
      intraepithelial neoplasia and thus may warrant a tissue diagnosis. Patients who
      have PanIN III (carcinoma in situ) can consider the option of pancreatectomy. The
      widespread and multifocal nature of PanIN changes throughout the entire pancreas
      in high-risk patients would make a total pancreatectomy preferable over a partial
      surgery. Careful selection of patients, the timing of the operation, and an
      experienced team of gastroenterologists, pancreatic surgeons, pathologists, and
      diabetologists are the keys to a good surveillance program and good outcomes for
      the patient.

PMID- 16107247
TI  - Effect of chronic ethanol ingestion on Purkinje and Golgi cell firing in vivo and
      on motor coordination in mice.
AB  - As motor coordination impairment is a common symptom of acute and chronic alcohol
      intoxication, different studies have been conducted on cerebellar Purkinje cell
      sensitivity to ethanol since Purkinje cell firing constitutes the final
      integrative output of the cerebellar cortex. However, the effects of chronic
      ethanol ingestion on Purkinje firing and other cerebellar neurons such as Golgi
      cells remain unknown. Here, we studied the extracellular discharge of Purkinje
      and Golgi cells in four groups of non-anesthetized mice drinking ad libitum
      either 0%, 6%, 12% or 18% ethanol isocallorically compensated with sucrose 25%
      during a 3-month period. No difference in Golgi cell firing was found with
      respect to ethanol consumption. The only group that presented significant
      differences in Purkinje cell firing compared to the other groups was the 18%
      ethanol-drinking group. These mice presented decreased simple spike and complex
      spike firing and increased complex spike duration and pause. The 18% ethanol
      drinking group was also the only one to present a slight but significant motor
      coordination impairment (evaluated by rotarod and runway) in naive task. No motor
      coordination impairment was noticed in task learned before ethanol consumption.
      These results suggest that chronic high doses of ethanol are necessary to produce
      Purkinje cell firing alterations and measurable motor coordination impairment in
      naive task. These alterations in Purkinje cell firing did not affect the ability
      to learn or to recall a motor coordination task.

PMID- 16107248
TI  - The complex pattern of SMAD signaling in the cardiovascular system.
AB  - The SMAD (small mother against decapentaplegic) family comprises transcription
      factors that function as signal transducers of TGFbeta (transforming growth
      factor) superfamily members. The number of studies showing expression, activation
      or involvement of both SMAD and TGFbeta family members in cardiovascular diseases
      is constantly rising. In this context, the position of SMADs in the diseased
      heart is particularly interesting because, besides their well-known fibrotic
      effects, increasing evidence demonstrates direct action of SMADs on
      cardiomyocytes as well as on the vascular system. In these systems, SMAD proteins
      are described to have effects on heart development, cell proliferation, cell
      growth, and apoptosis. As will be discussed in this review, these different
      consequences of SMAD activation are dependent on different SMAD isoforms,
      interaction of SMAD with other transcription factors in the particular situation,
      and modulation of SMAD activity by various kinases. As a result of all these
      influences, it turns out that activation of SMAD by members of the BMP (bone
      morphogenetic protein) family, which is a subfamily of the TGFbeta superfamily,
      is necessary for correct heart development. On the other hand, activation of
      SMADs by TGFbeta family members results in fibrotic, apoptotic, and anti
      hypertrophic processes that are related to a detrimental cardiac remodeling and
      progression to heart failure.

PMID- 16107249
TI  - Low tolerance and dependence liabilities of etizolam: molecular, functional, and
      pharmacological correlates.
AB  - The effects of prolonged exposure to and subsequent withdrawal of the
      thienotriazolobenzodiazepine etizolam on gamma-aminobutyric acid (GABA) type A
      receptor gene expression and function were compared with those of the
      benzodiazepine lorazepam. Exposure of rat hippocampal neurons in culture to 10
      microM etizolam for 5 days reduced the amounts of alpha5 and gamma2S receptor
      subunit mRNAs, whereas etizolam withdrawal was associated with a persistent
      reduction in gamma2S mRNA and an increase in alpha2 and alpha3 mRNAs. Neither
      chronic exposure to nor withdrawal of etizolam affected the acute modulatory
      effects of etizolam or lorazepam on GABA-evoked Cl- current. Treatment with 10
      microM lorazepam for 5 days reduced the amounts of alpha1 and gamma2S subunit
      mRNAs and increased that of alpha3 mRNA, whereas lorazepam withdrawal was
      associated with persistence of the changes in alpha3 and gamma2S mRNAs and an
      increase in alpha2 and alpha4 mRNAs. Parallel changes in the abundance of alpha1
      and alpha4 subunit proteins induced by chronic exposure to and withdrawal of
      lorazepam, but not etizolam, were detected by immunocytofluorescence analysis.
      Chronic lorazepam treatment resulted in a reversible reduction in the modulatory
      efficacy of this drug and conferred on flumazenil the ability to potentiate GABA
      evoked Cl- current. The anticonvulsant action of etizolam was not altered in mice
      chronically treated with this drug, whereas lorazepam-treated animals became
      tolerant to the acute anticonvulsant effect of this benzodiazepine. These data
      suggest that etizolam is endowed with a reduced liability to induce tolerance and
      dependence compared with classical benzodiazepines.

PMID- 16107250
TI  - Structural domains in RNAi.
AB  - Structural and biochemical studies have begun to elucidate the pathway of RNA
      silencing that leads to the formation of the RISC complex. The outstanding
      feature of this pathway is the precise recognition and processing of double
      stranded RNA. We present a review of recent structures that illustrate the
      molecular mechanisms contributing to these two related functions, highlighting
      models of Drosha, Dicer, and RISC function.

PMID- 16107251
TI  - A novel strong competitive inhibitor of complex I.
AB  - Alkaline incubation of NADH results in the formation of a very potent inhibitor
      of complex I (NADH:ubiquinone oxidoreductase). Mass spectroscopy (molecular mass
      equal to 696) and absorption spectroscopy suggest that the inhibitor is derived
      from attachment of two oxygen atoms to the nicotinamide moiety of NADH. The
      inhibitor is competitive with respect to NADH with a K(i) of about 10(-8)M. The
      inhibitor efficiently suppresses NADH-oxidase, NADH-artificial acceptor
      reductase, and NADH-quinone reductase reactions catalyzed by submitochondrial
      particles, as well as the reactions catalyzed by either isolated complex I or the
      three subunit flavoprotein fragment of complex I.

PMID- 16107252
TI  - Requirements of myocyte-specific enhancer factor 2A in zebrafish cardiac
      contractility.
AB  - Myocyte-specific enhancer factor 2A (MEF2A) regulates a broad range of
      fundamental cellular processes including cell division, differentiation and
      death. Here, we tested the hypothesis that MEF2A is required in cardiac
      contractility employing zebrafish as a model organism. MEF2A is highly expressed
      in heart as well as somites during zebrafish embryogenesis. Knock-down of MEF2A
      in zebrafish impaires the cardiac contractility and results in sarcomere assembly
      defects. Dysregulation of cardiac genes in MEF2A morphants suggests that
      sarcomere assembly disturbances account for the cardiac contractile deficiency.
      Our studies suggested that MEF2A is essential in cardiac contractility.

PMID- 16107253
TI  - 2.45 GHz radiofrequency fields alter gene expression in cultured human cells.
AB  - The biological effect of radiofrequency (RF) fields remains controversial. We
      address this issue by examining whether RF fields can cause changes in gene
      expression. We used the pulsed RF fields at a frequency of 2.45 GHz that is
      commonly used in telecommunication to expose cultured human HL-60 cells. We used
      the serial analysis of gene expression (SAGE) method to measure the RF effect on
      gene expression at the genome level. We observed that 221 genes altered their
      expression after a 2-h exposure. The number of affected genes increased to 759
      after a 6-h exposure. Functional classification of the affected genes reveals
      that apoptosis-related genes were among the upregulated ones and the cell cycle
      genes among the downregulated ones. We observed no significant increase in the
      expression of heat shock genes. These results indicate that the RF fields at 2.45
      GHz can alter gene expression in cultured human cells through non-thermal
      mechanism.

PMID- 16107254
TI  - The dinuclear iron-oxo ferroxidase center of Pyrococcus furiosus ferritin is a
      stable prosthetic group with unexpectedly high reduction potentials.
AB  - Recombinant ferritin from Pyrococcus furiosus expressed in Escherichia coli
      exhibits in EPR monitored redox titrations a mixed valence (Fe(3+)-Fe2+) S=1/2
      signal at intermediate potentials that is a high-resolution homolog of the
      ferroxidase signal previously described for reconstituted horse spleen apo
      ferritin. P. furiosus reconstituted apo-ferritin reduced to intermediate
      potentials exhibits the same mixed-valence signal, which integrates to close to
      one spin per subunit. The reduction potentials of +210 and +50 mV imply that the
      iron dimer is a stable prosthetic group with three redox states.

PMID- 16107255
TI  - Histidine inhibits oxidative stress- and TNF-alpha-induced interleukin-8
      secretion in intestinal epithelial cells.
AB  - We investigated the effect of several amino acids on the secretion of such
      inflammatory cytokines as interleukin-8 (IL-8) induced by hydrogen peroxide or
      tumor necrosis factor-alpha (TNF-alpha) in intestinal epithelial-like Caco-2 and
      HT-29 cells. We found that histidine, one of the conditionally essential amino
      acids, significantly inhibited both hydrogen peroxide- and TNF-alpha-induced IL-8
      secretion and mRNA expression in Caco-2 cells and HT-29 cells. These inhibitions
      were dose dependent and the inhibition rate of hydrogen peroxide-induced IL-8
      secretion reached more than 50% at a concentration of 25mM, with over 95%
      inhibition at a concentration of 50mM. TNF-alpha increased the transcriptional
      activity of the IL-8 promoter which was significantly inhibited by treating Caco
      2 cells with histidine. Histidine also abolished the NF-kappaB-dependent
      activation of the IL-8 promoter induced by TNF-alpha. These results indicate that
      histidine inhibited the hydrogen peroxide- and TNF-alpha-induced IL-8 secretion
      at the transcriptional level in intestinal epithelial cells, suggesting that
      histidine has the potential to attenuate intestinal inflammation.

PMID- 16107256
TI  - LEAFY COTYLEDON 2 activation is sufficient to trigger the accumulation of oil and
      seed specific mRNAs in Arabidopsis leaves.
AB  - LEAFY COTYLEDON 2 (LEC2) is a key regulator of seed maturation in Arabidopsis. To
      unravel some of its complex pleiotropic functions, analyses were performed with
      transgenic plants expressing an inducible LEC2:GR protein. The chimeric protein
      is functional and can complement lec2 mutation. Interestingly, the induction of
      LEC2 leads to the accumulation of storage oil in leaves. In addition, short-term
      induction and use of translation inhibitors allowed to demonstrate that LEC2 can
      directly trigger the accumulation of seed specific mRNAs. Consistent with these
      results, the expression of three other major seed regulators namely, LEC1, FUS3,
      and ABI3 were also induced by LEC2 activation.

PMID- 16107257
TI  - Why a clinic fails to reach basic EmOC status: an editorial comment on three
      papers in this issue.

PMID- 16107258
TI  - An acid dissociation bridging ELISA for detection of antibodies directed against
      therapeutic proteins in the presence of antigen.
AB  - Bridging Enzyme-Linked Immunosorbent Assay (ELISA) is commonly used in detection
      of antibodies directed against therapeutic proteins. Advantages of the bridging
      ELISA include the capability to detect antibodies regardless of their isotype or
      the species of origin. However, detection of antibodies can be difficult, if not
      impossible, in the presence of high levels of the antigen in the sample matrix.
      This protocol describes a bridging ELISA that uses a covalently coupled high
      density antigen surface combined with an acid dissociation step to allow for
      antibody detection in the presence of antigen in human serum.

PMID- 16107259
TI  - Antihyperalgesic, but not antiallodynic, effect of melatonin in nerve-injured
      neuropathic mice: Possible involvements of the L-arginine-NO pathway and opioid
      system.
AB  - The present study was undertaken to determine the effects of
      intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) melatonin on
      mechanical allodynia and thermal hyperalgesia in mice with partial tight ligation
      of the sciatic nerve, and how the nitric oxide (NO) precursor l-arginine and the
      opiate antagonist naloxone influence this effect. A plantar analgesic meter was
      used to assess thermal hyperalgesia, and nerve injury-induced mechanical
      hyperalgesia was assessed with von Frey filaments. 1-5 weeks following the
      surgery, marked mechanical allodynia and thermal hyperalgesia developed in
      neuropathic mice. Intracerebroventricular and intraperitoneal melatonin, with its
      higher doses, produced a blockade of thermal hyperalgesia, but not mechanical
      allodynia. Administration of both l-arginine and naloxone, at doses which
      produced no effect on their own, partially reversed antihyperalgesic effect of
      melatonin. These results suggest that although it has different effects on
      neuropathic pain-related behaviors, melatonin may have clinical utility in
      neuropathic pain therapy in the future. It is also concluded that l-arginine-NO
      pathway and opioidergic system are involved in the antihyperalgesic effect of
      melatonin in nerve-injured mice.

PMID- 16107260
TI  - Comparison of growth and exploratory behavior in mice fed an exclusively milk
      formula diet and mice fed a food-pellet diet post weaning.
AB  - An exclusively milk formula diet stunted the growth of mice immediately following
      weaning. Milk-fed mice displayed a low-frequency profile of exploratory behavior,
      while pellet-fed mice showed high-frequency exploration. In contrast to
      exploratory behavior, feeding behavior did not differ significantly between milk-
      and pellet-fed mice. Despite showing low-frequency exploratory behavior, mice on
      an exclusively milk formula diet showed no difference in behavioral activities
      analyzed by an automatic hole-board apparatus compared to pellet-fed mice. These
      results suggest that the growth stunt caused by an exclusively milk formula diet
      retards the acquisition of active exploratory behavior without affecting the
      emotional state of mice.

PMID- 16107261
TI  - Opposite changes in imidazoline I2 receptors and alpha2-adrenoceptors density in
      rat frontal cortex after induced gliosis.
AB  - Opposite age-dependent changes in alpha2-adrenoceptor and imidazoline I2 receptor
      (I2-IRs) density have been related to brain gliosis development with aging. To
      check this hypothesis we applied in rats a model of reactive gliosis induced by
      heat. The specific binding of [3H]idazoxan (0.5-20 nM) in the presence of (
      )adrenaline (5 x 10(-6) M) to membranes from rat brain cortex showed that the
      density of I(2)-IRs was significantly higher in membranes of injured cortex
      (Bmax=60+/-6 fmol/mg protein; n=9) than in control (Bmax=38+/-3 fmol/mg protein;
      n=9; p=0.0053). Conversely, the density of alpha2-adrenoceptors, measured by
      [3H]clonidine (0.25-16 nM), in the injured cortex (Bmax=75+/-4 fmol/mg protein;
      n=9) was significantly lower than in sham membranes (Bmax=103+/-7 fmol/mg
      protein; n=9; p=0.0035). No significant differences in receptor's affinity were
      observed between both groups. These results support the hypothesis that gliosis
      induces opposite changes in alpha2-adrenoceptor and I2-IR density.

PMID- 16107262
TI  - Effects of progesterone on apneic events during behaviorally defined sleep in
      male rats.
AB  - Drug therapy with progesterone has been applied to the patients with sleep apnea
      syndrome, but its clinical efficacy is equivocal. In the present study, we
      examined the effects of progesterone (1 and 30 mg/kg, i.p.) on the apneic events
      during behaviorally defined sleep in male rats at 4, 14 and 26 weeks of age by
      using a whole body plethysmographic measurement. The number of events of
      spontaneous apnea (SA) and post-sigh apnea (PSA) increased with aging. The
      duration of SA or PSA was also prolonged in old rats. A low dose (1 mg/kg) of
      progesterone significantly decreased the number of both SA and PSA, and this
      effect increased in an age-dependent manner. However, progesterone had no effect
      on the duration of SA and PSA. Neither the basal respiratory rate nor the total
      sleep time was changed. On the other hand, a higher dose (30 mg/kg) of
      progesterone had no effect on the number of SA and PSA, while it prolonged the
      duration of PSA. It also prolonged the total sleep time without affecting the
      basal respiratory rate. Pretreatment with mifepristone (5 mg /kg, i.p.), an
      antagonist of progesterone receptors, inhibited the effects of the low dose of
      progesterone, but did not show any antagonistic effect on the high dose-induced
      changes. These results suggest that the progesterone-mediated mechanisms are
      involved, at least partly, in respiratory function during sleep and the
      progesterone therapy is possibly effective within an appropriate dose range for
      the sleep apnea syndrome.

PMID- 16107263
TI  - Endobain E, a brain endogenous factor, is present and modulates NMDA receptor in
      ischemic conditions.
AB  - We have isolated from rat cerebral cortex an endogenous Na(+), K(+)-ATPase
      inhibitor, termed endobain E, which modulates glutamatergic N-methyl-d-aspartate
      (NMDA) receptor. This endogenous factor allosterically decreases
      [(3)H]dizocilpine binding to NMDA receptor, most likely acting as a weak channel
      blocker. In the present study we investigated whether endobain E is present in
      the cerebral cortex of rats subjected to ischemia and modulates NMDA receptor
      exposed to the same conditions. Ischemia-reperfusion was carried out by bilateral
      occlusion of common carotid arteries followed by a 15-min reperfusion period.
      Elution profile of brain soluble fraction showed that endobain E is present in
      cerebral cortex of ischemia-reperfusion rats. On assaying its effect on
      synaptosomal membrane Na(+), K(+)-ATPase activity and [(3)H]dizocilpine binding
      to cerebral cortex membranes prepared from animals without treatment, it was
      found that the endogenous modulator isolated from ischemia-reperfusion rats was
      able to inhibit both enzyme activity and ligand binding. On the other hand,
      endobain E prepared from rats without treatment also decreased binding to
      cerebral cortex or hippocampal membranes obtained from animals exposed to
      ischemia-reperfusion. Since ischemia decreases tissue pH and NMDA receptor
      activity varies according to proton concentration, pH influence on endobain E
      effect was tested. Endobain E ( approximately 80 mg original tissue) decreased
      [(3)H]dizocilpine binding 25% at pH 7.4 or 8.0 but 90% at pH 6.5. These results
      demonstrate that endobain E is present and also able to modulate NMDA receptor in
      the short-term period that follows cerebral ischemia and that its effect depends
      on proton concentration, suggesting greater NMDA receptor modulation by endobain
      E at low pH, typical of ischemic tissues.

PMID- 16107264
TI  - Reactive oxygen species scavenging capacity of different cooked garlic
      preparations.
AB  - It was studied if the ability of aqueous garlic extracts to scavenge superoxide
      anion (O(2)(*-)), hydrogen peroxide (H(2)O(2)), and hydroxyl radical (OH(*)) is
      altered in the following aqueous preparations: (a) extracts of boiled garlic
      cloves (BG), (b) extracts of microwave-treated garlic cloves (MG), and (c)
      extracts of pickled garlic (PG), and heated extracts of (a) garlic powder (HGP)
      and (b) raw garlic (HRG). The data were compared with the unheated raw garlic
      (RG) or with the unheated garlic powder (GP). Extracts of GP and RG scavenged
      O(2)(*-), H(2)O(2), and OH(*) in a concentration-dependent way. The reactive
      oxygen species scavenging capacity was not decreased in the aqueous garlic
      extracts except in MG and HRG (for O(2)(*-)) and in HGP and PG (for H(2)O(2)).
      The heating before or after garlic cutting was unable to eliminate the capacity
      of the extracts to scavenge H(2)O(2), O(2)(*-), and OH(*).

PMID- 16107265
TI  - Inhibitory effect of Curcuma comosa on NO production and cytokine expression in
      LPS-activated microglia.
AB  - Curcuma comosa is an indigenous plant of Thailand, which has been traditionally
      and widely used as an anti-inflammatory agent for the treatment of postpartum
      uterine bleeding and uterine inflammation. However, the scientific investigation
      on its anti-inflammatory activity has not been reported. In the present study, we
      investigated the anti-inflammatory effect of the extract from C. comosa on the
      responses in microglia stimulated with lipopolysaccharide (LPS). Pretreatment of
      highly aggressively proliferating immortalized (HAPI) cells, a rat microglial
      cell line, with the hexane extract of C. comosa rhizome at 10(-9) to 10(-5) g/ml
      significantly suppressed the levels of NO released from these cells. The
      attenuation in iNOS protein and mRNA expression was also observed suggesting an
      interference at transcriptional level. In addition, C. comosa extract inhibited
      interferon regulatory factor-1 expression which is an essential transcription
      factor governing the iNOS expression. Moreover, the levels of mRNA expressions of
      MCP-1 and IL-6 induced by LPS were also prominently decreased in the presence of
      C. comosa extract. These results suggest that C. comosa extract possesses a
      strong anti-inflammatory activity and has a potential to be developed as a
      therapeutic compound for diverse neurological disorders associated with
      inflammation.

PMID- 16107266
TI  - Absorption and enterohepatic circulation of baicalin in rats.
AB  - Pharmacokinetics of baicalin, in form of its parent drug (BG) and conjugated
      metabolites (BGM), were studied following intravenous and oral administration of
      baicalin to intact rats. The enterohepatic circulation of BG and BGM was also
      assessed in a linked-rat model. Multiple plasma and urine samples were collected,
      and concentrations of BG and BGM were determined using a liquid
      chromatography/tandem mass spectrometry method. The concentration of BGM was
      assayed in the form of baicalein after treatment with beta
      glucuronidase/sulfatase. After i.v. administration, plasma concentration of BG
      rapidly declined with the elimination half-life (T1/2) of 0.1 till 4 h post dose,
      followed by slight increase from 4-8 h in plasma concentrations after drug
      administration. These plasma concentrations resulted in a significant
      prolongation of the terminal elimination half-life of BG (T1/2 TER, 9.7 h). BG
      also displayed slight increase in plasma concentrations (12-24 h) after oral
      administration, with T1/2 TER of 12.1 h. Based on the AUC of BG and BGM, the
      absolute bioavailability of baicalin was 2.2+/-0.2% and 27.8+/-5.6%,
      respectively. The exposure of baicalin to the systemic circulation was
      approximately 118-fold lower than that of BGM after oral administration (AUC0-t,
      4.43 versus 523.97 nmol.h/mL). The high extent of glucuronidation suggested the
      possible presence of enterohepatic circulation, which was confirmed in the linked
      rat model since plasma concentrations of BG and BGM were observed in bile
      recipient rats at 4 to 36 h. The extent of enterohepatic circulation after
      intravenous administration of baicalin was 4.8% and 13.3% for BG and BGM,
      respectively. It was determined that 18.7% and 19.3% of the administered baicalin
      were subjected to enterohepatic circulation for BG and BGM, respectively, after
      oral administration. These results confirm that BG undergoes extensive first-pass
      glucuronidation and that enterohepatic circulation contributes significantly to
      the exposure of BG and BGM in rats.

PMID- 16107267
TI  - Inhibition of cyclooxygenase-2 enhances myocardial damage in a mouse model of
      viral myocarditis.
AB  - To determine critical role of cyclooxygenase-2 (COX-2) for development of viral
      myocarditis, a mouse model of encephalomyocarditis virus-induced myocarditis was
      used. The virus was intraperitoneally given to COX-2 gene-deficient heterozygote
      mice (COX-2+/-) and wild-type mice (WT). We examined differences in heart
      weights, cardiac histological scores, numbers of infiltrating or apoptotic cells
      in myocardium, cardiac expression levels of COX-2, tumor necrosis factor-alpha
      (TNF-alpha), and adiponectin mRNA, immunoreactivity of COX-2, TNF-alpha, and
      adiponectin in myocytes, cardiac concentrations of TNF-alpha and adiponectin,
      prostaglandin E2 (PGE2) levels in hearts, and viral titers in tissues between COX
      2+/- and WT. We observed significantly decreased expression of COX-2 mRNA and
      reactivity in hearts from COX-2+/- on day 8 after viral inoculation as compared
      with that from WT, together with elevated cardiac weights and severe inflammatory
      myocardial damage in COX-2+/-. Cardiac expression of TNF-alpha mRNA, reactivity,
      and protein on day 8 was significantly higher in COX-2+/- than in WT, together
      with reciprocal expression of adiponectin mRNA, reactivity, and protein in
      hearts. Significantly reduced cardiac PGE2 levels on day 8 were found in COX-2+/-
      compared with those in WT. There was no difference in local viral titers between
      both groups on day 4. Infected WT treated with a selective COX-2 inhibitor, NS
      398, also showed the augmented myocardial damage on day 8. These results suggest
      that inhibition of COX-2 may enhance myocardial damage through reciprocal cardiac
      expression of TNF-alpha and adiponectin in a mouse model of viral myocarditis.

PMID- 16107268
TI  - Immunomodulatory compounds from Pestalotiopsis leucothes, an endophytic fungus
      from Tripterygium wilfordii.
AB  - The immunomodulatory effects of three compounds designated BS, GS, and YS
      produced by Pestalotiopsis leucothes, an endophytic fungus isolated from
      Tripterygium wilfordii, were evaluated. The 50% inhibition concentration (IC50)
      value of BS in the proliferative assay with various stimulating agents such as
      phytohemagglutinin-M (PHA-M), phorbol myristate acetate (PMA)/ionomycin, mixed
      lymphocyte reaction (MLR) and poke weed mitogen (PWM) was 0.35, 1.6, 0.8 and 5.4
      microg/ml, respectively. In addition, BS significantly inhibited the production
      of cytokines such as interleukin (IL)-1beta, IL-2, interferon (IFN)-gamma and
      tumor necrosis factor (TNF)-alpha, by peripheral blood mononuclear cells (PBMNC)
      and soluble IL-2 receptor expression at concentrations greater than 1 microg/ml.
      Inhibition of PHA stimulated PBMNC proliferation and IL-2 and sIL-2R production
      by BS indicates that it is a T-cell specific immunosuppressant. However, BS also
      moderately inhibited immunoglobulin (Ig) G and M at concentrations greater than 1
      mug/ml suggesting that it also has B cell immunosuppressive effects. YS was 10%
      less active than BS in all assay systems. In contrast, GS exhibited both
      suppression and enhancement of PBMNC proliferation in the presence of various
      stimulants. However, GS inhibited PWM stimulated PBMNC proliferation and IL-4 and
      IgG and IgM production at concentrations above 1 mug/ml. All three fungal
      compounds altered the percentage of T-lymphocyte subpopulations only at high
      concentrations. Cell viability was not affected at the immunosuppressive
      concentrations of these compounds. In conclusion, work from our laboratory has
      identified three potentially potent immunomodulatory compounds from P. leucothes.
      These compounds have variable effects on T- and B-cells and monocytes. They may
      partially explain the immunosuppressive activity of T. wilfordii. In addition,
      they may represent a new source of immunomodulatory compounds for the treatment
      of human immune mediated diseases.

PMID- 16107269
TI  - Inhibitory effect of mitragynine, an analgesic alkaloid from Thai herbal
      medicine, on neurogenic contraction of the vas deferens.
AB  - The effect of an indole-alkaloid mitragynine isolated from the Thai medicinal
      herb kratom (Mitragyna speciosa) on neurogenic contraction of smooth muscle was
      studied in guinea-pig vas deferens. Mitragynine inhibited the contraction of the
      vas deferens produced by electrical transmural stimulation. On the other hand,
      mitragynine failed to affect the responses to norepinephrine and ATP. Mitragynine
      did not reduce KCl-induced contraction in the presence of tetrodotoxin, prazosin
      and alpha,beta-methylene ATP. Mitragynine inhibited nicotine- or tyramine-induced
      contraction. By using the patch-clamp technique, mitragynine was found to block T
      and L-type Ca2+ channel currents in N1E-115 neuroblastoma cells. In the Ca2+
      measurement by a fluorescent dye method, mitragynine reduced KCl-induced Ca2+
      influx in neuroblastoma cells. The present results suggest that mitragynine
      inhibits the vas deferens contraction elicited by nerve stimulation, probably
      through its blockade of neuronal Ca2+ channels.

PMID- 16107270
TI  - Overview of mechanisms of cancer chemopreventive agents.
AB  - Epidemiological data provide evidence that it is possible to prevent cancer and
      other chronic diseases, some of which share common pathogenetic mechanisms, such
      as DNA damage, oxidative stress, and chronic inflammation. An obvious approach is
      avoidance of exposure to recognized risk factors. As complementary strategies, it
      is possible to render the organism more resistant to mutagens/carcinogens and/or
      to inhibit progression of the disease by administering chemopreventive agents. In
      a primary prevention setting, addressed to apparently healthy individuals, it is
      possible to inhibit mutation and cancer initiation by triggering protective
      mechanisms either in the extracellular environment or inside cells, e.g., by
      modifying transmembrane transport, modulating metabolism, blocking reactive
      species, inhibiting cell replication, maintaining DNA structure, modulating DNA
      metabolism and repair, and controlling gene expression. Tumor promotion can be
      counteracted by inhibiting genotoxic effects, favoring antioxidant and anti
      inflammatory activity, inhibiting proteases and cell proliferation, inducing cell
      differentiation, modulating apoptosis and signal transduction pathways, and
      protecting intercellular communications. In a secondary prevention setting, when
      a premalignant lesion has been detected, it is possible to inhibit tumor
      progression via the same mechanisms, and in addition by affecting the hormonal
      status and the immune system in various ways, and by inhibiting tumor
      angiogenesis. Although tertiary prevention, addressed to cancer patients after
      therapy, is outside the classical definition of chemoprevention, it exploits
      similar mechanisms. It is also possible to affect cell-adhesion molecules, to
      activate antimetastasis genes, and to inhibit proteases involved in basement
      membrane degradation.

PMID- 16107271
TI  - Lymphocyte Hprt mutant frequency and sperm toxicity in C57BL/6 mice treated
      chronically with Azathioprine.
AB  - Many patients undergoing chronic therapy with the purine analogue Azathioprine
      (Aza) have highly elevated HPRT lymphocyte mutant frequencies (MFs), and it is
      likely that these increases are due to selection of pre-existing HPRT mutant
      lymphocytes. A similar selection in germ cells might result in an increased
      frequency of the Lesch-Nyhan syndrome. In this study, a mouse model for Aza
      mutant selection was developed and Aza toxicity was evaluated in the germ cells
      of treated mice. Groups of 20 male C57BL/6 mice were treated by gavage three
      times/week with 0, 5, 10, 25, 50, or 100mg/kg Aza, and three to eight mice from
      each group were sacrificed at various times for up to 23 weeks. Mice treated with
      25-100mg/kg Aza were all dead by 14 weeks of treatment. Hprt lymphocyte MF assays
      indicated that the treated mice had reduced numbers of spleen lymphocytes. Most
      treated mice had Hprt MFs similar to those of control mice (2.1+/-1.6 x 10(-6)),
      however, highly elevated MFs were detected in one out of three mice given 5mg/kg
      for 10 weeks, one out of three mice given 10mg/kg for 10 weeks, and one out of
      eight mice given 10mg/kg for 23 weeks (e.g., 233 x 10(-6) after 10 weeks of
      5mg/kg). Sequence analysis of Hprt cDNA indicated that all mutant clones from one
      of these mice had a T-->A transversion in the initiation codon. Multiplex-PCR on
      mutant clones from the other two mice indicated that all the clones from one had
      a deletion of Hprt exons 2 and 3, while most of the mutants from the other had
      lost all of the Hprt exons. Measurements of testicular weight, and of sperm
      count, viability, morphology, and motility found that Aza produced low levels of
      toxicity in sperm, with the most consistent effect being a reduction in the
      testicular weight. The data suggest that mice chronically treated with 5 and
      10mg/kg Aza (doses similar to those used in humans) have elevated Hprt MFs due to
      clonal amplification of selected Hprt mutants. The results also suggest that mice
      treated with these doses of Aza retain reasonable fertility, and will be useful
      for breeding experiments to examine the possibility of increasing the germ-line
      transmission of Hprt mutations.

PMID- 16107272
TI  - Cross state-dependent retrieval between histamine and lithium.
AB  - Histamine and lithium state-dependent (StD) retrieval of passive avoidance task
      and their interactions was examined in mice. The pre-training or pre-test
      intracerebroventricular (i.c.v.) injection of histamine (20 microg/mouse)
      impaired retrieval when it was tested 24 h later. In the animals, in which
      retrieval was impaired due to histamine pre-training administration, pre-test
      administration of histamine, with the same dose, restored retrieval. The H1
      blocker, pyrilamine (20 microg/mouse, i.c.v.), but not the H(2) blocker;
      ranitidine prevented the restoration of retrieval by pre-test histamine. The pre
      training (5 and 10 mg/kg) or pre-test (5 mg/kg) injection of lithium also
      impaired retrieval, when it was tested 24 h later. In the animals that received
      lithium (5 mg/kg) or histamine (20 microg/mouse) as pre-training treatment,
      administration of histamine, clobenpropit or lithium, respectively, resulted in
      restoration of memory retrieval. Neither pyrilamine nor ranitidine prevented the
      restoration of retrieval by pre-test lithium. In conclusion, histamine or lithium
      can induce state-dependent retrieval and a cross-StD exists between these drugs,
      which may be mediated through the inositol pathway.

PMID- 16107273
TI  - Active trachoma in children in central Ethiopia: association with altitude.
AB  - A cross-sectional study was conducted in the dry month of February 2000 in the
      Gurage Zone of Ethiopia (population over 1.5 million) to determine the magnitude
      of trachoma and blindness. A multistage cluster sampling was applied to identify
      the study subjects. Pre-school children (1-6 years) were examined for active
      trachoma by trained ophthalmic nurses. The prevalence of active trachoma in the 1
      6-year-old age group was 56.5%, ranging from 5.7% (altitude > 3000 m) to 73.4%
      (altitude less than 2000 m) (P < 0.001). Active trachoma was more common in male
      children than in female children and peaked in the 3-year-old age group (63.2%),
      declining with age. The distance to a source of water for 45% of these households
      was only 15 min. Only 6% of the households had latrines. Confirmation of the
      association between active disease and altitude may assist with mapping of
      trachoma in Ethiopia and elsewhere. It is possible that fly density, higher in
      villages at low altitudes, contributed to the differences seen.

PMID- 16107274
TI  - Microelectronics mounted on a piezoelectric transducer: method, simulations, and
      measurements.
AB  - This paper describes the design of a highly integrated ultrasound sensor where
      the piezoelectric ceramic transducer is used as the carrier for the driver
      electronics. Intended as one part in a complete portable, battery operated
      ultrasound sensor system, focus has been to achieve small size and low power
      consumption. An optimized ASIC driver stage is mounted directly on the
      piezoelectric transducer and connected using wire bond technology. The absence of
      wiring between driver and transducer provides excellent pulse control
      possibilities and eliminates the need for broad band matching networks. Estimates
      of the sensor power consumption are made based on the capacitive behavior of the
      piezoelectric transducer. System behavior and power consumption are simulated
      using SPICE models of the ultrasound transducer together with transistor level
      modelling of the driver stage. Measurements and simulations are presented of
      system power consumption and echo energy in a pulse echo setup. It is shown that
      the power consumption varies with the excitation pulse width, which also affects
      the received ultrasound energy in a pulse echo setup. The measured power
      consumption for a 16 mm diameter 4.4 MHz piezoelectric transducer varies between
      95 microW and 130 microW at a repetition frequency of 1 kHz. As a lower
      repetition frequency gives a linearly lower power consumption, very long battery
      operating times can be achieved. The measured results come very close to
      simulations as well as estimated ideal minimum power consumption.

PMID- 16107275
TI  - Ca2+ signalling and Ca2+-activated ion channels in exocrine acinar cells.
AB  - The development of the calcium signalling field, from its early beginnings some
      40 years ago to the present, is described. Calcium signalling in exocrine gland
      acinar cells and the effects of neurotransmitter- or hormone-elicited rises in
      the cytosolic calcium ion concentration on ion channel gating are reviewed. The
      highly polarized arrangement of the organelle systems in living acinar cells is
      described as well as its importance for the physiologically relevant local and
      polarized calcium signalling events.

PMID- 16107276
TI  - Distribution of pesticides, PAHs and heavy metals in prawn ponds near Kolleru
      lake wetland, India.
AB  - This paper discussed the distribution of pesticides, polycyclic aromatic
      hydrocarbons (PAHs) and heavy metals in water, sediment and prawn from intensive
      prawn ponds (n=8) near the Kolleru lake wetland, India and assessed the quality
      of prawn for human consumption and also discussed the possible effects of these
      pollutants on pond environment and aquatic environment. The chemicals and other
      products used in prawn ponds near the Kolleru lake wetland were documented. The
      sediment, prawn and water samples were collected six times from selected prawn
      ponds during the production period of 3 months. Water samples were analyzed for
      selected physico-chemical parameters. The levels of pesticides, PAHs and heavy
      metals were found to decrease in the order sediment followed by prawn and water.
      The maximum concentrations of pesticides in sediment, prawn and water were alpha
      BHC (174.2 microg g(-)(1)), gamma-BHC (234 microg g(-)(1)), malathion (256 microg
      g(-)(1)), chloripyrifos (198.5 microg g(-)(1)), endosulfan (238 microg g(-)(1)),
      dieldrin (19.6 microg g(-)(1)) and p,p'-DDT (128.6 microg g(-)(1)). Isodrin was
      found below detectable limit. The maximum concentrations of PAHs in sediment,
      prawn and water are anthracene (0.901 microg kg(-)(1)), fluranthene (0.601 microg
      kg(-)(1)), pyrene (0.786 microg kg(-)(1)), chrysene (0.192 microg kg(-)(1)),
      benzo(a)pyrene (0.181 microg kg(-)(1)) and benzo(ghi)perylene (227 microg kg(
      )(1)). Benzo(e)pyrene, perylene, isomers of dibenzoanthracene and coronene were
      found below detectable limits. The maximum concentrations of heavy metals in
      sediment, prawn and water and also in prawn feed are Cu (791 microg g(-)(1)), Pb
      (270 microg g(-)(1)), Cd (1.07 microg g(-)(1)), Mn (4417 microg g(-)(1)), Ni (8.1
      microg g(-)(1)), Co (5.8 microg g(-)(1)), Zn (1076 microg g(-)(1)), Cr (36.4
      microg g(-)(1)), As (2.9 microg g(-)(1)), Se (6.3 microg g(-)(1)), Th (2.1 microg
      g(-)(1)) and Mo (0.762 microg g(-)(1)).

PMID- 16107277
TI  - Trafficking of peripheral blood CD56(bright) cells to the decidualizing uterus-
      new tricks for old dogmas?
AB  - CD56(bright) lymphocytes become abundant in the human uterus during every
      menstrual cycle, following the surge in pituitary-derived luteinizing hormone
      (LH), which initiates final oocyte maturation. While the uterus is host to some
      CD56(bright) cells prior to ovulation, the rapid increase is thought to be due to
      proliferation of the resident population, accompanied by recruitment of
      CD56(bright) lymphocytes from the circulation. The rapid increase in CD56(bright)
      cells is concurrent with the onset of decidualization, the transformation of
      uterine stromal cells into secretory decidual cells. Uterine CD56(bright) cells
      proliferate and differentiate to become the predominant lymphocytes of the post
      ovulatory uterus. These distinct, tissue-specific natural killer (NK) cells
      either die prior to menses or increase in number during early pregnancy, and then
      decline toward the end of the first trimester. Since lymphocytes home to tissues
      from the circulation, we investigated mechanisms of NK cell traffic over the
      course of natural menstrual cycles by measuring functional interactions between
      CD56+ cells from blood and endothelial cells using the Stamper-Woodruff assay of
      lymphocyte adhesion to frozen tissue sections. While a baseline level of adhesion
      was maintained throughout the cycle, elevated l-selectin-dependent adhesion of
      peripheral blood CD56(bright) cells occurred during a peri-ovulatory window.
      However, there were no significant menstrual cycle-induced changes in the
      transcription of l-selectin, alpha 4 integrin or LFA-1, or in expression of these
      proteins by NK cells, suggesting that the enhanced adhesion was due to post
      translational modifications of these molecules. Quantitative RT-PCR failed to
      amplify the message for LH receptor or the alpha or beta forms of progesterone or
      estrogen receptors from blood NK cell subsets. Thus, we conclude that the actions
      of LH, E(2,) and P(4) on NK cells that promote interactions with endothelium and
      potential uterine homing are indirectly mediated through the responsiveness of
      other cell types.

PMID- 16107278
TI  - Antigenic epitope for sperm-immobilizing antibody detected in infertile women.
AB  - CD52 is a glycosylphosphatidylinositol (GPI) anchor protein occurring in
      lymphocytes, the epididymis, seminal plasma and on ejaculated sperm surface. The
      molecular structure of male reproductive tract CD52 (mrtCD52) is quite different
      from that of lymphocyte CD52 except for a peptide sequence comprising 12 amino
      acids. The carbohydrate molecule may thus provide antigenic epitopes to females.
      The repeated N-acetyllactosamine units of the N-linked carbohydrate present in
      the mrtCD52 were identified as a pathogenic antigen for infertility using a
      monoclonal antibody (MAb H6-3C4) generated from an infertile patient's peripheral
      blood lymphocyte. We suggested also the possible presence of O-linked
      carbohydrate in human mrtCD52, although it is not known whether this carbohydrate
      is immunogenic or not. This article gives an overview of the structure and
      function of mrtCD52 as well as the fertilization-blocking mechanism of the
      antibody against this molecule.

PMID- 16107279
TI  - Activation of CD1d-independent NK1.1+ T cells in the large intestine by
      Lactobacilli.
AB  - Among digestive organs, the liver and the large intestine are abundant in T cells
      expressing NK1.1. NK1.1+ T cells in the liver are mostly CD1d-dependent whereas
      those in the large intestine are CD1d-independent. In this study, we investigated
      the effects of Lactobacilli on NK1.1+ T cells in the digestive organs of mice.
      C57BL/6 mice were orally given a dietary supplement prepared from mixed cultures
      of eight strains of Lactobacilli. Oral administration of Lactobacilli to mice
      resulted in the selective expansion of NK1.1+ T cells in the large intestine.
      These colon NK1.1+ T cells activated by Lactobacilli were found to express IFN
      gamma mRNA. The level of IFN-gamma in the serum was also elevated by the
      administration of Lactobacilli. Our results suggest that Lactobacilli selectively
      activate CD1d-independent NK1.1+ T cells in the large intestine to produce IFN
      gamma and therefore modulate Th1 immune responses.

PMID- 16107281
TI  - Glucocorticoid receptor antagonism in the basolateral amygdala and ventral
      hippocampus interferes with long-term memory of contextual fear.
AB  - The binding of glucocorticoids to the type II or glucocorticoid receptor (GR) is
      known to play a role in memory consolidation and long-term memory. The present
      series of studies investigated the locus for GR effects on learning and memory of
      contextual fear conditioning. The GR antagonist RU 38486 was administered
      peripherally (10, 20, or 30 mg/kg/ml), as well as centrally into the lateral
      ventricle (75 or 150 ng/2 microL), basolateral amygdala (BLA; 0.3, 3, or 30
      ng/0.2 microL), dorsal hippocampus (DH; 30 ng/microL) or ventral hippocampus (VH;
      30 ng/microL) prior to contextual fear conditioning. Peripheral administration of
      RU 38486 did not affect fear-related levels of freezing immediately following a
      footshock or in a long-term memory test 24 h later. However, administration into
      the lateral ventricle, BLA, or VH decreased freezing in a 24 h retention test,
      while leaving post-shock levels of freezing intact. Both post-shock and retention
      levels of freezing were unaffected in rats that received RU 38486 in the DH
      compared to vehicle controls; however, vehicle rats also displayed low levels of
      freezing during retention. The data indicate that GR activation within the BLA
      and VH is important for the establishment of long-term memory for contextual fear
      conditioning.

PMID- 16107282
TI  - Hyperphagia of hyperthyroidism: is neuropeptide Y involved?
AB  - The possible role of neuropeptide Y (NPY) was studied in rats with
      hypermetabolism and hyperphagia induced by thyroxine (50-100-200 microg/day s.c.
      for 3-4 weeks). Both metabolic rate and body temperature increased quickly with
      thyroxine treatment, while hyperphagia started to develop only after 2 weeks of
      treatment. The weight gain rate progressively decreased or stopped. The NPY
      induced hyperphagia was not altered significantly during thyroxine treatment (in
      severe thyrotoxicosis it was rather suppressed); the fasting-induced hyperphagia
      was smaller than in controls following 1 week of treatment, and it became
      enhanced only after 3 weeks, when the deficit in body weight indicated a certain
      level of starvation already prior to the food deprivation. The NPY-antagonist D
      Tyr27,36,D-Thr32-NPY27,36 suppressed this fasting-induced hyperphagia, suggesting
      that endogenous NPY is involved in this late phase. In conclusion,
      hyperthyroidism per se does not increase the NPY activity, instead the quickly
      developing hyperthermia may inhibit the NPY actions; NPY may, however, be
      activated by a concurrent hypermetabolism-induced starvation.

PMID- 16107283
TI  - Bayesian spatio-temporal modelling of national milk-recording data of seasonal
      calving New Zealand dairy herds.
AB  - A spatio-temporal analysis was undertaken with the aim of identifying the
      dynamics of herd mean individual cow SCCs (MICSCC) in seasonally calving New
      Zealand dairy herds. Two datasets were extracted from the Livestock Improvement
      Corporation's extensive national dairy recording database: (1) milk-recording
      data aggregated at the herd-level and (2) sales questionnaire data containing
      information on the size, location and infrastructure of each farm. A Bayesian
      spatio-temporal modelling approach was applied to the analysis. The data were
      aggregated by 10 km(2) grid cells and linear regression models were developed
      with spatially structured and unstructured random effects, a linear temporal
      trend random effect and spatial-temporal interactions for log-transformed median
      MISCC (ln(median MISCC)). Significant associations were found between ln(median
      MISCC) and milk yield, milk fat, milk protein, farm area and number of cups in
      the dairy. This led us to suggest that SCCs should be adjusted for volume and
      constituents prior to determining a threshold MISCC for identification of
      subclinical mastitis (SCM) problem herds. Part, or all, of the temporal trend in
      MISCC in the spatio-temporal model was accounted for by inclusion of yield and
      milk constituents as independent variables. This supports the hypothesis of a
      dilution effect with potential consequences for misdiagnosis of SCM, particularly
      in late lactation. Unmeasured covariates were similarly likely to be spatially
      structured and unstructured.

PMID- 16107284
TI  - Information and consumer choice: the value of publicized health plan ratings.
AB  - We use data on the enrollment decisions of federal annuitants to estimate the
      influence of publicized ratings on health plan choice. We focus on the impact of
      ratings disseminated by the National Committee for Quality Assurance (NCQA), and
      use our estimates to calculate the value of the information. Our approach
      exploits a novel feature of the data-the availability of non-public plan ratings
      to correct for a source of bias that is inherent in studies of consumer
      responsiveness to information on product quality: since publicized ratings are
      correlated with other quality signals known to consumers (but unobserved by
      researchers), the estimated influence of ratings is likely to be overstated. We
      control for this bias by comparing the estimated impact of publicized ratings to
      the estimated impact of ratings that were never disclosed. The results indicate
      that NCQA's plan ratings had a meaningful influence on individuals' choices,
      particularly for individuals choosing a plan for the first time. Although we
      estimate that a very small fraction of individual decisions were materially
      affected by the information, for those that were affected the implied utility
      gains are substantial.

PMID- 16107285
TI  - Agrobacterium-mediated transformation of Sclerotinia sclerotiorum.
AB  - Ascospores from the phytopathogenic fungus Sclerotinia sclerotiorum were
      transformed to hygromycin B resistance by co-cultivation with Agrobacterium
      tumefaciens. Transformed spores germinated and grew on PDA supplemented with 100
      ug/ml hygromycin B. The presence of mitotically stable hph gene integration at
      random sites in the genome was confirmed by PCR and Southern blot analysis. A
      transformation frequency of 8 x 10(-5) was achieved in five separate experiments.
      This study is the first report of success co-cultivating A. tumefaciens with S.
      sclerotiorum. This report of a reproducible Agrobacterium-mediated transformation
      method should allow the development of T-DNA tagging as a system for insertional
      mutagenesis in S. sclerotiorum and provide a simple and reliable method for
      genetic manipulation.

PMID- 16107286
TI  - Construction of random transposition mutagenesis system in
      Rhodococcuserythropolis using IS1415.
AB  - Recent studies on the metabolic activities of genus Rhodococcus have shown
      rhodococci to be of important use in industrial, pharmaceutical and environmental
      biotechnology. The increasing economic significance of Rhodococcus encourages
      renewed efforts to characterize their genetic systems, as Rhodococcus genetics
      are still poorly understood. The goal of this study is to adapt a transposon
      system for use in creating random mutagenesis in Rhodococcus erythropolis. A
      plasmid carrying IS1415, a member of IS21 family identified from Rerythropolis,
      has been constructed and designated as pTNR. pTNR is a non-replicating transposon
      tool introduced into target cells by electroporation. During its transposition,
      the transposable-marker gene is separated from the open reading frames (istAB) of
      IS1415, which should avoid secondary transposition. Transposition of pTNR into
      wild-type R. erythropolis created mutagenesis with a high efficiency of
      1.23x10(6)mutants per microgram plasmid DNA. However, it could also be transposed
      into other Rhodococcus spp. at lower frequencies in comparison with that of R.
      erythropolis. It has been indicated by Southern hybridization that the generated
      kanamycin-resistant mutants were resulted from single transposition event of
      pTNR. The results also revealed that the transposable-marker gene of pTNR was
      randomly inserted into the chromosomal DNA of R. erythropolis. The affected DNA
      regions carrying the transposed DNA element could be conveniently recovered for
      further characterization using a plasmid rescue procedure. Sequence data of the
      insertion sites of 40 random mutants analyzed indicated that transposition of
      pTNR generated 6-bp direct target duplications in 36 cases, while in the
      remaining four mutants; it generated 5- or 7-bp target duplications (two cases
      each). This study concluded that pTNR could be served as an efficient genetic
      tool for construction of random mutagenesis system in Rhodococcus species.

PMID- 16107287
TI  - Minimization of aggregation of secreted bivalent anti-human T cell immunotoxin in
      Pichia pastoris bioreactor culture by optimizing culture conditions for protein
      secretion.
AB  - In a bioreactor culture of genetically engineered Pichia pastoris secreting a
      bivalent immunotoxin, 64% of the secreted immunotoxin was present in aggregate
      forms and this resulted in a loss of bioactivity. Biochemical analyses of the
      secreted immunotoxin and an in vitro aggregation study using purified monomeric
      immunotoxin suggested that aggregation was primarily an extracellular event. By
      employing limited methanol feeding at 0.75 mlmin(-1) per 10l initial medium,
      oxygen consumption was reduced, permitting a lowering of the bioreactor agitation
      speed from 800 to 400 rpm. By increasing the anti-foam reagent to 0.6 mll(-1),
      the thickness of the air/liquid interfacial foam layer was reduced by 80%. These
      steps reduced the immunotoxin aggregates from 64% to 5%. Consequently immunotoxin
      purification yield was increased from 53.0% to 73.8%. Simultaneously this
      methodology enhanced immunotoxin secretion to 120 mgl(-1) at 163 h of methanol
      induction in a toxin resistant production strain. We conclude that minimizing
      shearing force and reducing the air/liquid interfacial foam area are crucial
      factors in reducing hydrophobic protein aggregation upon secretory expression in
      yeast bioreactor cultures.

PMID- 16107288
TI  - Incorporation and release of cloxacillin sodium in micelles of poly(styrene-b-2
      vinyl pyridine-b-ethylene oxide).
AB  - A novel drug carrier system was constructed from anionic drug cloxacillin sodium
      (CLX) and micelle of poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) (PS-PVP
      PEO) by incorporating the former into the micelle of the latter. The
      incorporation of CLX into the micelle of PS-PVP-PEO was confirmed by zeta
      potential measurements, dynamic light scattering (DLS), and fluorescence
      spectroscopy. In the absence of the anionic drug, CLX, the zeta-potential of neat
      PS-PVP-PEO micelle was +13 mV under aqueous acidic condition due to the presence
      of positive charges in the PVP unit. The addition of CLX into the micelle of PS
      PVP-PEO decreased the zeta-potential of the micelle smoothly and finally led to a
      minimum zeta-potential around 0 mV. This fact shows that the added CLX is
      effectively incorporated into the PS-PVP-PEO micelle by electrostatic attraction.
      In concomitant with the decrease in zeta-potential, a decrease in hydrodynamic
      diameter from 94 to 69 nm was observed on addition of CLX to the PS-PVP-PEO
      micellar solution. This fact also indicates the incorporation of CLX into the PS
      PVP-PEO micelles because the binding of CLX to the PVP block of the micelles
      induces a conformational change from an extended to a shrunken form due to the
      cancellation of the repulsive force in the PVP blocks by CLX. Fluorescence
      quenching of pyrene by CLX gave additional evidence for the effective bindings of
      CLX to the PS-PVP-PEO micelles. Further, release of CLX from the nanoaggregates
      of CLX/PS-PVP-PEO was investigated in vitro. It was found that the release
      kinetics of the CLX is conformed to a model based on the consecutive chemical
      kinetics.

PMID- 16107289
TI  - Late pregnancy blood pressure in nulliparas and subsequent abnormal glucose
      tolerance.
AB  - A growing body of evidence indicates that pregnancy-induced hypertension can be
      associated with features of insulin resistance. However, the impact of lower than
      hypertension-levels of blood pressure in pregnancy on the subsequent risk of
      developing abnormal glucose tolerance (AGT), has not been examined. We
      investigated women born in the years 1933-1956 and living in the municipality of
      Savitaipale, Finland, in May 1996. Prevalence of AGT was assessed by using oral
      glucose tolerance tests (OGTT). A retrospective chart review was carried out with
      regard to 216 nulliparas to obtain late pregnancy blood pressures. Logistic
      regression analyses showed that, after adjusting for body mass index (BMI) and
      age at OGTT, as well as for the number of subsequent pregnancies and the use of
      antihypertensive medication for PIH, 1 mmHg increase in systolic and diastolic
      blood pressure at late pregnancy in nulliparas increased the probability for AGT
      later in life 1.04-fold (OR, 1.04; 95% confidence interval, 1.00-1.09) and 1.06
      fold (OR, 1.06; 95% confidence interval, 1.02-1.11), respectively. The results of
      this study suggest that not only hypertension but also less elevated levels of
      blood pressure during late pregnancy in nulliparas may be used as a predictor of
      subsequent AGT.

PMID- 16107290
TI  - Prevalence of diabetes in Murcia (Spain): a Mediterranean area characterised by
      obesity.
AB  - The aim of this cross-sectional study was to describe the prevalence of total,
      known and unknown diabetes mellitus and impaired fasting glucose (IFG) in the
      population of Murcia (SE Spain), a Mediterranean area with a high prevalence of
      obesity. Therefore, 2562 subjects (>or=20 years) were selected by stratified
      random sampling and a survey was carried out by telephone, together with a
      physical examination and biochemical determinations. The ADA-1997 diagnostic
      criteria were used. The crude prevalence of total diabetes was 11% (9.5-12.6%),
      known diabetes 7.8% (6.5-9.2%), unknown diabetes 3.2% (2.4-4.2%) and IFG 4.9%
      (3.9-6.1%). Both total diabetes and IFG were higher in men than in women, with
      prevalence rates increasing with age. People with diabetes and IFG had higher
      BMI, blood pressure, total cholesterol, LDL-cholesterol and triglyceride values
      than the rest of the population. No difference in the prevalence of diabetes was
      observed between the rural and urban populations. The prevalence of diabetes in
      Murcia is high compared to the rest of Spain and the world, suggesting that the
      possible benefits attributed to some characteristics of the diet of this
      Mediterranean population are not sufficient to counteract the risk factors
      associated with the disease.

PMID- 16107291
TI  - A baseline survey of the Primary Healthcare system in south eastern Nigeria.
AB  - A baseline survey to audit the PHC operations and determine community perception
      and expectations of PHC service delivery was conducted in 72 communities in Enugu
      state, southeastern Nigeria. The study was intended to facilitate the development
      of intermediate performance indicators for monitoring the progress of an ongoing
      health sector reform and to gather baseline data for planning and policy
      formulation. The tools used for the operations audit assessed indicators for
      evaluating: (a) Stewardship, (b) Service Provision and (c) Administrative and
      financial management; while the community survey was assessed by, (a) utilization
      of health services, (b) perception of service delivery and (c) health care
      financing. One hundred and sixteen respondents from each of the facilities in the
      sample frame were interviewed using a structured self-assessment questionnaire
      and a qualitative assessment was undertaken in 53 of the facilities using an
      audit guide. Focus group discussions (FGD) were conducted with the policy makers
      and planners in each of the 17 LGAs in the state. A total of 832 respondents were
      interviewed in the communities (using a structured questionnaire) and 42
      community FGDs were conducted. The results indicate a lack of operational
      efficiency in the majority of the facilities audited. It was also observed that
      majority of the facilities do not provide all services required of it, are poorly
      maintained, do not have enough skilled health workers and operate without a
      budget. There appears to be no formal financial management system in place and no
      policy on financial resource generation. The community survey identified two
      major problems; low utilization of PHCs and poor service provision. The key
      indicator identified by the community for evaluating performance of the PHCs
      remains "access to essential drugs". The major prospect was the willingness of an
      appreciable number of respondents to invest in health financing through insurance
      schemes and payment of health tax among others. It was evident that poor funding,
      bad management practices and infrastructural decay is the bane of efficient PHC
      delivery. Consequently, we propose that cost determination studies, to establish
      the financial implication of the minimum package for provision of primary
      healthcare services, should be an essential prerequisite to the reform process.
      Some critical cross-cutting issues identified from the data obtained which could
      form the basis for major policy thrust include, development of strategies for
      sustainable promotion of public-private-partnership for enhanced community
      involvement in healthcare management, ensuring that interventional investment is
      proportional to the felt health needs of the populace and funding of healthcare
      through equitable integration of user fees/charges.

PMID- 16107292
TI  - Steroid-induced alterations in mRNA expression of the long form of the prolactin
      receptor in the medial preoptic area of female rats: Effects of exposure to a
      pregnancy-like regimen of progesterone and estradiol.
AB  - It is firmly established that the onset of maternal behavior in the female rat is
      stimulated by a combination of hormones that include prolactin (PRL), estradiol
      (E2), and progesterone (P(4)). Specifically, nulliparous rats display short
      latencies to respond to foster young when primed with Silastic capsules filled
      with P4 and E2 and then administered PRL centrally to the medial preoptic area
      (MPOA), an area integrally involved in the expression of maternal behavior in
      this species. PRL or P4 treatments alone are ineffective in stimulating the
      expression of maternal care. Since the actions of PRL in the MPOA appear to be
      mediated by PRL receptors, it was of interest to determine whether and how
      treatment with P4 and E2 together or separately might alter mRNA expression of
      the long form of the PRL receptor (PRL-R(L)) in the MPOA. Using in situ
      hybridization histochemistry (ISHH), mRNA expression of the PRL-R(L) was measured
      in the MPOA of ovariectomized, nulliparous rats treated with various combinations
      of P4 and E2. Treatment of animals with P4 alone for 10 days or with P4 followed
      by E2 for 1 or 4 days resulted in reductions in PRL receptor mRNA expression in
      the MPOA when compared with the expression in animals treated with E2 alone or
      blank capsules. The actions of P4 on mRNA expression of the PRL-R(L) were more
      pronounced in the dorsal MPOA. Circulating PRL levels collected at the time of
      sacrifice were elevated in all groups treated with E2, but no association between
      PRL levels and receptor mRNA expression within the MPOA was evident. These
      findings indicate that the dorsal MPOA may be one site of progesterone's action
      in facilitating prolactin-mediated maternal behavior.

PMID- 16107293
TI  - Poor antibody response to pneumococcal polysaccharide vaccination suggests
      increased susceptibility to pneumococcal infection in splenectomized patients
      with hematological diseases.
AB  - Patients with hematological diseases undergoing diagnostic or therapeutic
      splenectomy are at increased risk of pneumococcal infections. Vaccination is a
      straightforward option in preventing these infections. A well-defined cohort of
      splenectomized patients with hematological disorders was followed according to
      response to 23-valent pneumococcal capsular polysaccharide (Pneumovax N)
      vaccination. A total of 76 splenectomized patients (Hodgkin lymphoma, HL 26, non
      Hodgkin lymphoma, NHL 19, immune-mediated cytopenias 28, and others 3) with a
      median age of 52 years (range 18-82 years) were included. Pneumococcal
      polysaccharide (PS) antibodies were determined using an enzyme-linked
      immunosorbent assay before vaccination, at peak, and follow-up. A poor response
      to vaccination was observed in 21 (28%) patients and a good response in 55 (72%),
      respectively. During the follow-up period of 7.5 years (range 3.5-10.5 years)
      after vaccination, and despite repeated revaccination in many cases, a total of
      five episodes (in three patients) of pneumococcal infections were reported, all
      confined to the poor responder group. Revaccination did not improve antibody
      levels in this group. The median age at vaccination was significantly higher in
      the group of poor responders (p=0.0006). None of the following factors could
      predict a poor antibody response: gender, disease activity or aggressiveness in
      hematological malignancies, previous radiotherapy and/or chemotherapy, time
      between splenectomy and pneumococcal vaccination, time between
      chemotherapy/radiotherapy and study pneumococcal vaccination (1 year), or the
      presence of hypogammaglobulinemia. In conclusion, a substantial proportion of
      splenectomized patients with hematological diseases mounted a poor PS antibody
      response and remained at risk for pneumococcal infections despite vaccination. In
      the absence of apt indirect clinical predictors of antibody response, with the
      exception of age, measurement of antibody levels seems to be a feasible method
      for early identification of this patient subgroup. Poor responders do not benefit
      from revaccination, and should be offered other prophylactic measures.

PMID- 16107294
TI  - Immunogenicity and effectiveness of Haemophilus influenzae type b conjugate
      vaccine in HIV infected and uninfected African children.
AB  - The quantitative (anti-Hib capsular polysaccharide antibody concentrations; anti
      HibPS) and qualitative (bactericidal activity and avidity) aspects in immune
      responses to Haemophilus influenzae type b polyribosyl ribitol phospshate
      CRM(197) conjugate vaccine (HibCV; HibTiter) were evaluated in 66 HIV infected
      children not receiving anti-retroviral therapy and 127 HIV uninfected children.
      Surveillance was conducted for invasive Hib disease in a cohort of 39,865
      (approximately 6.4% of whom were HIV infected) children from March 1998 to June
      2004. HIV infected children had lower anti-HibPS geometric mean antibody
      concentrations 1 month post-immunisation than HIV uninfected children (P<0.00001)
      and were less likely to have anti-HibPS antibody concentrations of >or=1.0
      microg/ml (RR 0.54; 95% CI 0.43-0.69). A lower proportion of HIV infected
      children than HIV uninfected children (RR 0.78; 95% CI 0.66-0.93) had measurable
      anti-Hib serum bactericidal activity (SBA) and the HibPS antibody concentration
      required for 50% killing of Hib bacteria was greater among HIV infected than HIV
      uninfected children (P=0.001). The estimated risk of HibCV failure was 35.1-fold
      greater (95% CI 14.6-84.6) amongst HIV infected than HIV uninfected children.

PMID- 16107295
TI  - Lower border reducer for symphyseal and parasymphyseal fractures of mandible: a
      new device.

PMID- 16107296
TI  - Verruciform xanthoma coexisting with oral discoid lupus erythematosus.
AB  - We describe an unusual case of verruciform xanthoma on the lingual surface of the
      gum that coexisted with oral discoid lupus erythematosus.

PMID- 16107297
TI  - Feasibility study of the retrospective use of the Adult Comorbidity Evaluation
      index (ACE-27) in patients with cancer of the head and neck who had radiotherapy.
AB  - The Adult Comorbidity Evaluation index (ACE-27) is a relatively new measure of
      comorbidity and the aim of this study was to assess the feasibility of
      retrospective examination of casenotes to estimate this index in patients who
      were given radiotherapy for head and neck cancer. We examined the casenotes of
      157 of 168 consecutive patients diagnosed with an index primary tumour of the
      head and neck at the Clatterbridge Centre of Oncology in 1992 and 1993. Three
      comorbidity measures, the ACE-27, Charlson comorbidity index (CL) and Washington
      University Head Neck Cancer Index (WUHNCI) were calculated. In the grading of the
      ACE-27, 5 patients (3%) were grade 3, 21 (13%) were grade 2, 57 (36%) were grade
      1 and 74 (47%) were grade zero. There was a trend in survival by ACE-27 grading
      with little difference between mild and moderate severity (p=0.08). There were no
      significant correlations between survival and either the Charlson index (p=0.80)
      or the WUHNCI (p=0.68). There were no significant correlations of any of the
      indices or of clinico-demographic factors with recurrence rates.

PMID- 16107298
TI  - Long-term outcome of secondary alveolar bone grafting in patients with various
      types of cleft.
AB  - OBJECTIVE: To evaluate the results of secondary alveolar bone grafting in
      patients with various types of cleft. DESIGN: One hundred and seventy patients
      were classified as cleft lip and alveolar process alone (CLAP), complete
      unilateral cleft lip and palate (UCLP), and complete bilateral cleft lip and
      palate (BCLP). The Bergland criteria were used to assess the long-term outcome of
      alveolar bone grafting. RESULTS: In the UCLP and BCLP groups, the success rate
      was significantly better (P<0.05) when the cleft was grafted before the eruption
      of canines. When the operation was done after the eruption of canines, there was
      a significant difference in the success rate between CLAP and BCLP (P<0.05).
      CONCLUSION: The timing of the operation was the critical variable that affected
      the outcome in patients with complete cleft lip and palate. The severity of the
      deformity influenced the success rate when alveolar bone grafting was done after
      the eruption of canines.

PMID- 16107299
TI  - Haemangiomas and vascular malformations of the maxillofacial region--a review.
AB  - Congenital vascular anomalies have been and remain poorly understood. Since 1982
      haemangiomas and vascular malformations have been recognised as distinct entities
      that exhibit unique characteristics and demand appropriately tailored treatment
      plans. However, "haemangioma" still continues to be used as a clinical and
      pathological description of many different types of vascular anomalies, which
      complicates both the care of patients and the interpretation of reports in
      journals. In this review we summarise the current classification, terminology,
      and the pathological basis of these lesions and discuss their management. The
      various therapeutic options available and their outcome will be discussed in
      addition to the recent advances in the psychosocial aspects of care,
      interventional radiology, laser and pharmacological therapy.

PMID- 16107300
TI  - Quantifying the influence of safety management on the reliability of safety
      barriers.
AB  - A methodology is described that enables to use safety management audit
      assessments and safety culture questionnaire results for estimating the
      reductions in the reliability of safety barriers in major hazard plants. The
      critical issue is the establishment of weight factors in combination with the
      anchoring of "good" safety management. A method is proposed to derive weight
      factors from statistical accident analysis in combination with a statistical
      analysis of safety management assessments at a representative sample of major
      hazard industries. A preliminary set of weight factors is presented with some
      examples of resulting reductions in reliability--this demonstration confirms that
      the set of weight factors needs further development.

PMID- 16107301
TI  - ARAMIS project: a more explicit demonstration of risk control through the use of
      bow-tie diagrams and the evaluation of safety barrier performance.
AB  - Over the last two decades a growing interest for risk analysis has been noted in
      the industries. The ARAMIS project has defined a methodology for risk assessment.
      This methodology has been built to help the industrialist to demonstrate that
      they have a sufficient risk control on their site. Risk analysis consists first
      in the identification of all the major accidents, assuming that safety functions
      in place are inefficient. This step of identification of the major accidents uses
      bow-tie diagrams. Secondly, the safety barriers really implemented on the site
      are taken into account. The barriers are identified on the bow-ties. An
      evaluation of their performance (response time, efficiency, and level of
      confidence) is performed to validate that they are relevant for the expected
      safety function. At last, the evaluation of their probability of failure enables
      to assess the frequency of occurrence of the accident. The demonstration of the
      risk control based on a couple gravity/frequency of occurrence is also possible
      for all the accident scenarios. During the risk analysis, a practical tool called
      risk graph is used to assess if the number and the reliability of the safety
      functions for a given cause are sufficient to reach a good risk control.

PMID- 16107302
TI  - A computational model to predict aortic wall stresses in patients with systolic
      arterial hypertension.
AB  - Computational cardiovascular mechanics has allowed scientists to create complex
      3D models for the simulation of cardiovascular problems. Mechanical stress plays
      a crucial role in the function of the cardiovascular system; stress analysis is a
      useful tool for the understanding of vascular pathophysiology. By using the
      spiral CT imaging and computational structural analysis, we present a noninvasive
      method of wall stress analysis in the normal aorta. The aortic segment was
      extended from the origin of the inferior mesenteric artery to the aortic
      bifurcation. The length of this segment was 12 cm, while the maximum transverse
      diameter was 2.075+/-0.129 cm. A 3D aortic model was constructed based on the CT
      scan images. The aorta was assumed to have a uniform wall thickness of 1.5mm. The
      generated unstructured grid, which was used for the structural analysis,
      consisted of 14,440 hexahedral elements. The wall material was assumed to be
      hyperelastic, homogeneous, isotropic and nearly incompressible (Poisson
      ratio=0.45). According to experimental studies, the Young modulus of aortic wall
      was set equal to 4.66 MPa. The shear stress induced by the blood flow was
      neglected. A finite-element static structural analysis was performed. Three
      different cases were examined applying constant intraluminal systolic blood
      pressures of 120, 180 and 240 mmHg, respectively. The von Mises stress
      distribution and the displacements of the aortic wall were calculated. Peak wall
      stress for the normal load case of 120 mmHg was 22.5 N/cm2, while the max
      displacement was 0.44 mm. The case with the intraluminal pressure of 180 mmHg
      resulted into peak wall stress of 32 N/cm2 with max displacement 0.59 mm, while
      for 240 mmHg was 40.6N/cm2, max displacement 0.72 mm. The rise in blood pressure
      caused all stresses to increase. The pattern of stress distribution and the
      orientation of the stress were similar for all test cases. A quantitative
      evaluation of the aortic wall stresses under systolic hypertension is presented.
      The calculated values of peak wall stress are far lower to those of failure
      strength of healthy aortic wall specimens estimated by ex vivo mechanical testing
      (121.0 N/cm2). Our values are consistent with prior stress values predicted by
      experimental studies. The described methodology offers a significant advancement
      in incorporating biomechanical principles in the clinical assessment of
      hypertensive patients with normal or aneurysmatic aortas and can be applied in a
      patient-specific basis in both conditions in order to detect the vulnerable high
      stressed regions and the resultant risk of aortic dissection or rupture. We
      hypothesize that this could assist in deciding the timing of surgical
      intervention, especially in high-risk patients with abdominal aortic aneurysms.

PMID- 16107303
TI  - A rare mRNA variant of the human lymphocyte-specific protein tyrosine kinase LCK
      gene with intron B retention and exon 7 skipping encodes a putative protein with
      altered SH3-dependent molecular interactions.
AB  - A rare mRNA variant of the human lymphocyte-specific protein tyrosine kinase LCK
      gene that retains intron B and excludes exon 7 (B+7-) due to alternative splicing
      of the canonical LCK transcripts was identified and characterized. LCK B+7- mRNA
      is detected in all tested peripheral blood T lymphocytes total RNA samples but is
      apparently sequestered in the nucleus. The presence of intron B sequence does not
      disrupt the reading frame and results in the insertion of 58 aminoacids,
      containing a proline-rich region just upstream of p56lck SH3 domain. This
      putative isoform encodes an unstable 516 aminoacids protein (LckB+7-) which can
      be expressed in transfected COS-7 cells. Furthermore in Jurkat T cell extracts, a
      recombinant intron B plus SH3 p56lck domain fails to interact with some TCR
      induced tyrosine phosphorylated polypeptides and known p56lck partners such as
      Sam68 and c-Cbl. The biological function of this rare messenger remains to be
      elucidated.

PMID- 16107304
TI  - Fetal and neonatal origins of altered brain development.
AB  - Abnormal development of the brain during fetal life is now thought to contribute
      to the aetiology of many neurological disorders that manifest throughout life.
      Many factors are likely to underlie such abnormal development including genetic
      makeup and an adverse intrauterine environment. This review will focus on
      prenatal hypoxic/ischaemic injury, inflammatory/infective insults and preterm
      birth. A range of experimental models have been used to characterize lesions
      formed in response to these insults and to determine mechanisms of damage
      resulting from such events. Relatively brief periods of fetal hypoxia result in
      neuronal death (cerebellum, hippocampus, and cerebral cortex), white matter
      damage and reduced growth of neural processes. These effects are more profound at
      mid than late gestation. Chronic mild placental insufficiency can result in fetal
      growth restriction and deficits in neural connectivity and myelination. Exposure
      of the preterm fetus to inflammatory agents causes brain damage particularly in
      the white matter and this is exacerbated by hypoxia. Premature birth without
      potentiating factors can result in subtle neuropathologies including cerebral
      white matter gliosis, hippocampal sclerosis and subarachnoid haemorrhage; the
      extent of the damage appears to be related to the regimen of ventilatory support.
      These studies show that the timing, severity and nature of specific insults are
      critical in determining the pattern of injury and thus the extent to which
      neurological function will be affected postnatally. Defining the causes, patterns
      and mechanisms of brain injury is crucial if we are to develop rational
      neuroprotective strategies to reduce the burden of altered brain growth and poor
      functional and behavioural outcomes.

PMID- 16107305
TI  - Subjective sleep disturbance and its correlates in middle-aged Hong Kong Chinese
      women.
AB  - OBJECTIVES: To examine the factors associated with subjective sleep disturbance
      in middle-aged Hong Kong Chinese women. METHODS: A total of 305 women aged 45-55
      years were recruited at community-based women's clubs. Eligible subjects were of
      Chinese ethnicity and not taking oral contraceptives, hormone therapy or had
      received surgical removal of ovary. Standardized questionnaires, including
      sociodemographic, health and life-style variables, Pittsburgh Sleep Quality Index
      (PSQI), Greene Climacteric Scale (GCS) and Perceived Stress Scale were
      administered. RESULTS: About 18% of the sample complained of difficulty
      initiating sleep, difficulty maintaining sleep or early morning awakening at
      least three times per week in the past month. About 26% of the women were poor
      sleepers as defined by a global PSQI score >5. Sleep difficulty was one of the
      five most commonly reported climacteric symptoms. Cross-sectional analysis found
      that significantly more peri- and postmenopausal women had subjective sleep
      disturbance than premenopausal women. Multiple logistic regression analysis
      showed that women who had high levels of somatic complaints, psychological
      symptoms and perceived stress had a four to sixfold increased risk of reporting
      disturbed sleep. Menopausal status was not an independent predictor. CONCLUSIONS:
      Comparison of our findings with recent literatures suggested a lower prevalence
      of insomnia in Hong Kong Chinese middle-aged females than Caucasian women.
      Somatic complaints, psychological symptoms and perceived stress were independent
      risk factors for sleep disturbance. Clinicians should screen for sleep problems
      in middle-aged Chinese women with prominent somatic and psychological symptoms
      and perceived stress.

PMID- 16107306
TI  - Trials of clear aceclofenac-loaded soft capsules with accelerated oral absorption
      in human subjects.
AB  - To develop an effective oral drug delivery system with accelerated absorption in
      human subjects for a poorly water-soluble acelofenac, five aceclofenac-loaded
      soft capsule preparations containing various ratios of different solubilizers
      were prepared and their dissolution tests were carried out. Among five
      preparations tested, a preparation with ethanolamine was selected as a formula of
      aceclofenac soft capsule (Korea United Pharm. Co. Ltd., Clanza S, since it was
      clear in appearance and showed the fastest dissolution rate due to the solubility
      enhancing effect of aceclofenac. To evaluate and compare the pharmacokinetics of
      acelofenac-loaded soft capsules with the conventional aceclofenac tablets (Dae
      Woong Pharm. Co. Ltd., Airtal) in human subjects; 14 normal healthy male
      volunteers (age 20-25 years old) were divided into two groups and a randomized 2
      x 2 cross-over study was performed. Following oral administration of one tablet
      or capsule, each containing 100mg of aceclofenac, blood samples were collected at
      the predetermined time intervals and the concentration of aceclofenac in plasma
      was determined by HPLC method using UV detector. The AUC, Cmax, MRT, t1/2 and Kel
      of aceclofenac delivered from soft capsule were not significantly different from
      those from aceclofenac-loaded conventional tablet. However, soft capsule gave
      significantly higher initial concentration and significantly faster Tmax of
      aceclofenac than did conventional tablet, suggesting that the soft capsule with
      ethanolamine showed the faster absorption of aceclofenac in human subjects. Thus,
      the clear aceclofenac-loaded soft capsule with ethanolamine was a more effective
      oral dosage form with fast absorption for poorly water-soluble aceclofenac.

PMID- 16107307
TI  - Biotinidase reveals the morphogenetic sequence in cochlea and cochlear nucleus of
      mice.
AB  - Hearing loss affects children with biotinidase deficiency, an inherited metabolic
      disorder in the recycling of biotin. The deficit appears shortly after birth
      during development of the auditory system. Using a mouse model, we sought to
      discover where and when biotinidase is expressed in the normal development of the
      cochlea and cochlear nucleus. In the process, we reconstructed the normal
      morphogenetic sequences of the constituent cells. Immunolabeling for biotinidase
      was localized to neurons and other cells of the adult and immature mouse,
      including the embryonic precursors of these regions dating from the stage of the
      otocyst. Its distribution was compared to the particular morphological changes
      occurring at each developmental stage. Biotinidase was localized in cells and
      their processes at the critical stages in their proliferation, migration,
      structural differentiation, and innervation, covering the entire span of their
      development. The prevalence of immunostaining peaked in the adult animal,
      including hair cells and ganglion cells of the cochlea and neurons of the
      cochlear nucleus. The findings suggest that biotinidase plays a role in the
      normal development of the auditory system. Besides the pattern of localization of
      biotinidase, this study provides the first systematic account of each
      developmental stage in a mammalian auditory system.

PMID- 16107308
TI  - Lower birth weight and attenuated adrenocortical response to ACTH in offspring
      from sows that orally received cortisol during gestation.
AB  - Prenatal stress is known to affect several offspring characteristics, but its
      effects depend among other factors on the period of gestation in which it is
      applied. In the present study, oral administration of hydrocortisone-acetate
      (HCA) was used to elevate cortisol concentrations in pregnant sows to levels also
      observed after psychological stress. HCA was administered during three different
      periods of gestation (115 days in pigs): period 1: 21-50 (P1, n = 10), period 2:
      51-80 (P2, n = 10) and period 3: 81-110 (P3, n = 10) days after insemination.
      Control sows (n = 11) received vehicle from 21-110 days after insemination. When
      P1-, P2- and P3-sows did not receive HCA, they also received vehicle. During
      gestation, weekly saliva samples were taken from the sows to determine salivary
      cortisol concentrations. Treatment effects on sow, litter and piglet
      characteristics were determined. In addition, two female piglets per litter were
      subjected to an ACTH-challenge test at 6 weeks of age to determine the
      adrenocortical response to ACTH. Pigs were slaughtered at 6 months of age and
      slaughter weight, back fat thickness and percentage of lean meat were analysed.
      During the period of treatment with HCA, salivary cortisol concentrations were
      increased in P1-, P2- and P3-sows compared to control sows (P < 0.01). The total
      number of piglets born per litter did not differ among treatment groups (P >
      0.30), but pooled HCA-litters had a higher percentage of live born piglets (P <
      0.05) and fewer mummies than control litters (P < 0.05). Gestation length did not
      differ among treatment groups (P = 0.21), but did affect treatment effects on
      birth weight. Overall, HCA-piglets weighed less at birth, and remained lighter
      until weaning (P < 0.05). The salivary cortisol concentrations after i.m.
      injection of ACTH (2.5 IU/kg) were lower in P1- and P3-piglets compared to
      control piglets. At slaughter, HCA-treatment indirectly decreased lean meat
      percentage and increased back fat thickness. In conclusion, elevated peripheral
      cortisol concentrations in pregnant sows affect both litter characteristics and
      piglet physiology, the latter depending on the period of gestation during which
      concentrations were elevated. Underlying mechanisms require further
      investigation.

PMID- 16107309
TI  - Sustained attention in young people at high risk of psychosis does not predict
      transition to psychosis.
AB  - Early detection of imminent psychosis allows for the possibility of interventions
      to prevent onset, or to minimise severity and disability. It also has potential
      to enhance knowledge of the factors important in the etiology of psychotic
      illnesses. Neurocognitive deficits are well documented in psychotic illnesses and
      there is evidence to suggest that such deficits are present in individuals long
      before they develop the illness. Further, it has been proposed that such
      impairments may indicate an underlying predisposition to develop psychosis and
      may thus be described as 'vulnerability indicators'. This study aimed to
      investigate the proposed vulnerability indicator of impaired sustained attention
      in young people thought to be at ultra high-risk of developing psychosis
      imminently to see whether it would improve the prediction of psychosis in this
      group. The Continuous Performance Test - Identical Pairs (CPT-IP) version
      performance of an ultra high-risk group (UHR, N=70) was compared with that of a
      healthy comparison group (NC, N=51) and a first-episode psychosis group (FEP,
      N=32). The UHR group exhibited performance deficits compared to the NC group and
      performed at a level similar to that of the FEP group. However, within the UHR
      group, those who developed psychosis within the timeframe of the study did not
      differ from those who did not develop psychosis on their CPT-IP performance.
      These results support sustained attention as an indicator of vulnerability to
      psychosis, but suggest that CPT-IP performance does not help to predict
      transition to psychosis in an ultra high-risk group.

PMID- 16107310
TI  - Effects of chronic treatment with fluvoxamine and paroxetine during adolescence
      on serotonin-related behavior in adult male rats.
AB  - Selective Serotonin Reuptake Inhibitors (SSRIs) are designed to treat adults, but
      are increasingly prescribed for adolescents. SSRIs might cause permanent changes
      in serotonin-related behavior in adolescents, since their serotonergic system is
      still developing. Male Wistar rats were treated with paroxetine (15 mg/kg p.o.)
      or fluvoxamine (30 mg/kg p.o.) throughout adolescence. After a washout period
      their behavior in the elevated plus-maze, prepulse inhibition test, Forced
      swimming test and elevated T-maze were studied. In addition, the effects of the 5
      HT(1A) receptor agonist 8-OH-DPAT on sexual behavior and lower lip retraction
      were measured. Paroxetine mildly inhibited weight gain during treatment. Both
      SSRIs caused a reduction in ejaculation frequency and in time spent on the open
      arm of the elevated plus-maze in adult rats. Fluvoxamine slightly increased
      avoidance latency in the elevated T-maze compared to paroxetine. No differences
      between the groups were found in the other tests. Apparently, chronic treatment
      with SSRIs during adolescence may cause mild changes in adult behavior.

PMID- 16107311
TI  - Colloidal stability of aqueous polymeric dispersions: effect of water insoluble
      excipients.
AB  - An important issue in the aqueous coating process is dispersion stability. An
      unstable dispersion results in aggregation of the colloidal particles, thereby
      affecting the film coating process. In the coating suspension containing pigment,
      a latex for aqueous film coating might interact with pigment, resulting in
      unstable dispersion. We therefore conducted a stability investigation in a mixed
      dispersion including latexes, EudragitL30D-55 (A-latex), EudragitRL30D (C-latex)
      and EudragitNE30D (N-latex) and pigments, titanium dioxide and iron oxide yellow.
      An aggregation of the dispersion containing A-latex was observed at pH 2.
      Regarding the dispersions with C-latex and N-latex, no aggregation was observed
      in the range pH 2-11. We calculated total interaction energy between latex-latex
      particles, pigment-pigment particles and latex-pigment particles based on DLVO
      theory. The calculated results explained two mechanisms of the stable mixed
      dispersion. The first was that the individual latex particle and the pigment
      particle dispersed without aggregation in the mixed dispersion because of the
      electrostatic interaction. The next was that the latexes adsorbed onto the
      surface of the pigments, making electrostatically stable heterocoaggregates. We
      also calculated the binding constant of iron oxide yellow for C-latex at pH 10.
      The value of the constant was determined to be 1.1 x 10(-2).

PMID- 16107313
TI  - Cadherins and catenins in breast cancer.
AB  - Recent studies show that cadherins and catenins are hormonally regulated and
      carry out physiological roles during mammary development but have pathological
      effects when deregulated. E-cadherin expression is irreversibly lost in invasive
      lobular breast cancer (ILC). Animal models of ILC provide mechanistic insight,
      confirming that E-cadherin serves as both a tumor suppressor and an invasion
      suppressor in ILC. Ductal breast cancer involves complex, reversible, epigenetic
      modulation of multiple cadherins. Transcriptional regulators of E-cadherin have
      been identified that induce epithelial-to-mesenchymal transitions. Catenins are
      lost or mislocalized in tumors lacking cadherins. However, beta-catenin signaling
      is upregulated by numerous pathways in >50% of breast tumors and animal models
      suggest its oncogenic function in breast relates to its role in mammary
      progenitor cell expansion.

PMID- 16107314
TI  - Delving into the diversity of facultative heterochromatin: the epigenetics of the
      inactive X chromosome.
AB  - X chromosome inactivation represents one of the most dramatic examples of mono
      allelic gene expression and long-term gene-silencing in mammals. The key
      regulatory molecule that triggers silencing is the Xist transcript, but little is
      known about its repressive action. Some progress has been made in deciphering the
      epigenetics of the inactive state that it triggers, however. During pre
      implantation development, the inactive state is relatively labile. Later on, in
      the soma, the inactive state is highly stable and clonally heritable. This is
      ensured by the panoply of epigenetic modifications that characterize the inactive
      X and, presumably, is also a result of its spatio-temporal segregation. The
      inactive X chromosome has been associated with an increasing number of histone
      modifications, and several recent studies have implicated Polycomb group proteins
      in laying down some of these marks. Thanks to genetic and biochemical approaches
      to analyse these proteins, the epigenetic tapestry of the inactive X is just
      beginning to be unravelled. Lineage-specific differences provide a glimpse into
      the developmental complexity of the epigenetic marks that ensure the inactive
      state.

PMID- 16107315
TI  - Impact of heavy metals on enzymatic activity of substrate and on composting worms
      Eisenia fetida.
AB  - The effect of heavy metals Cu and Zn on dehydrogenase and protease activity of
      the substrate during vermicomposting was investigated. Three dosages of Cu and Zn
      were tested in mesocosm experiments to investigate their bioaccumulation and
      impact on the reproduction of Eisenia fetida. Cu accumulated within the worm
      tissues in dosage concentrations up to a maximum level of 213 mg Cu kg(-1). The
      number of juveniles decreased from the lowest to highest dosages of Cu and Zn
      after 10 weeks of the experiment. Dehydrogenase showed a strong negative
      correlation (P < 0.01) with increased dosage of Cu, while protease remained
      unaffected. An overall reduction on dehydrogenase activity with increasing
      dosages of Cu and Zn indicated that these metals would impact detrimentally on
      the soil microbiology and consequently the stabilisation of the dosed media.

PMID- 16107316
TI  - Modification of the intrinsic fluorescence and the biochemical behavior of ATP
      after irradiation with visible and near-infrared laser light.
AB  - In this work, the effects of visible (655 nm) and near-infrared (830 nm) light on
      ATP in solution were examined. The addition of irradiated ATP to the hexokinase
      reaction caused significant differences in the reaction rates and in the
      Michaelis-Menten kinetic parameters, k(m) and v(max). Irradiated ATP cleavage by
      hexokinase occurred in less time. Changes were wavelength and dose dependent.
      Excitation of ATP with a 260 nm wavelength ultraviolet light induced a
      fluorescence emission that was decreased when Mg2+ was added due to ion binding
      of the phosphates, which are the structures that modify the fluorescence produced
      by the adenine dipoles. The irradiation of this ATP.Mg2+ solution using 655 and
      830 nm light increased the fluorescence by a possible displacement of Mg2+ from
      the phosphates. In conclusion, visible and near-infrared light modifies the
      biochemical behavior of ATP in the hexokinase reaction and the fluorescence
      intensity of the molecule thus altering the Mg2+ binding strength to the oxygen
      atoms in the phosphate group.

PMID- 16107317
TI  - N2 laser excited autofluorescence spectroscopy of formalin-fixed human breast
      tissue.
AB  - The paper reports results of an in vitro study on autofluorescence spectroscopy
      of fresh and formalin-fixed human breast tissue samples to investigate the effect
      of formalin fixation on the measured autofluorescence spectra. It also explores
      the applicability of the approach in discriminating cancerous from the uninvolved
      sites of the formalin-fixed breast tissues based on their autofluorescence
      spectra. A probability-based diagnostic algorithm, making use of the theory of
      relevance vector machine (RVM), a powerful recent approach for statistical
      pattern recognition, was developed for that purpose. The algorithm provided
      sensitivity values of up to 97% and specificity values of up to 100% towards
      cancer for both the independent validation data set as well as for the training
      data set based on leave-one-out cross-validation. These results suggest that
      autofluorescence spectroscopy may prove to be a valuable additional in vitro
      diagnostic modality in clinical pathology setting for discriminating cancerous
      tissue sites from normal sites.

PMID- 16107318
TI  - Early changes in Abeta levels in the brain of APPswe transgenic mice--implication
      on synaptic density, alpha7 neuronal nicotinic acetylcholine- and N-methyl-D
      aspartate receptor levels.
AB  - Tg 2576 (APPswe) mice develop age-related amyloid deposition as well as
      behavioural- and electrophysiological changes in the brain. In this study, APPswe
      mice were investigated from 7 to 90 days of age. We observed high Abeta levels in
      the cortex of APPswe mice at 7 days of age, suggesting that these mice produce
      Abeta from birth. A positive correlation between Abeta and synaptophysin levels,
      followed by changes in ERK MAPK activity, indicated that Abeta causes altered
      synaptic function and an increase in the number of synaptic terminals. In
      addition, alterations in [(125)I]alphabungarotoxin- and [(3)H]MK-801 binding
      sites were also observed in APPswe mice compared to controls. In conclusion, over
      expression of Abeta early in life causes changes in synaptophysin levels and
      number of [(125)I]alphabungarotoxin- and [(3)H]MK-801 binding sites. The results
      may provide important information about the onset and consequences of Abeta
      pathology in this transgenic mouse model.

PMID- 16107319
TI  - Automatic detection of spiking events in EMFi sheet during sleep.
AB  - In this paper we present a new method for detection of spiking events caused by
      the increased respiratory resistance (IRR) from ballistocardiographic (BCG) data
      recorded with EMFi sheet. Spiking is a phenomenon where BCG wave complexes
      increase in amplitude during IRR. In this study data from six patients with a
      total of 1503 visually scored spiking events were studied. The algorithm monitors
      amplitude levels of BCG complexes and detects large relative increases. In this
      work 10 different variations of the algorithm were compared in order to find the
      best variation, which can cope with different recordings. The best variation of
      the algorithm was able to detect spiking events with 80% true positive and 19%
      false positive rates. The detection is not dependent on absolute waveform
      amplitudes and therefore does not require any recording-specific tuning prior to
      application. It is important to recognize spiking events in order to evaluate the
      severity of respiratory disturbance during sleep.

PMID- 16107320
TI  - Anti-oxidant activity of spermine and spermidine re-evaluated with oxidizing
      systems involving iron and copper ions.
AB  - This study was designed to investigate the direction of redox reactions of
      spermine and spermidine in the presence of iron and copper. The redox activity of
      spermine and spermidine was assessed using a variety of methods, including their
      ability to: (1) reduce Fe(3+) to Fe(2+) ions; (2) protect deoxyribose from
      oxidation by Fe(2+)-ethylene diaminetetraacetic acid, Fe(3+)-ethylene
      diaminetetraacetic acid systems with and without H(2)O(2); (3) protect DNA from
      damage caused by Cu(2+)-H(2)O(2), and Fe(2+)-H(2)O(2) with and without ascorbic
      acid; (4) inhibit H(2)O(2)-peroxidase-induced luminol dependent
      chemiluminescence; (5) scavenge diphenyl-picryl-hydrazyl radical. Spermine and
      spermidine at concentration 1mM reduced 1.8+/-0.3 and 2.5+/-0.1 nmol of Fe(3+)
      ions during 20 min incubation. Both polyamines enhanced deoxyribose oxidation.
      The highest enhancement of 7.6-fold in deoxyribose degradation was found for
      combination of spermine with Fe(3+)-ethylene diaminetetraacetic acid. An 10mM
      spermine and spermidine decreased CuSO(4)-H(2)O(2)-ascorbic acid- and FeSO(4)
      H(2)O(2)-ascorbic-induced DNA damage by 73+/-6, 69+/-4% and 90+/-5, 53+/-4%,
      respectively. They did not protect DNA from CuSO(4)-H(2)O(2) and FeSO(4)
      H(2)O(2). Spermine apparently increased the CuSO(4)-H(2)O(2)-dependent injury to
      DNA. Polyamines attenuated H(2)O(2)-peroxidase-induced luminol dependent
      chemiluminescence. Total light emission from specimens containing 10mM spermine
      or spermidine was attenuated by 85.3+/-1.5 and 87+/-3.6%. During 20 min
      incubation 1mM spermine or spermidine decomposed 8.1+/-1.4 and 9.2+/-1.8% of
      diphenyl-picryl-hydrazyl radical. These results demonstrate that polyamines of
      well known anti-oxidant properties may act as pro-oxidants and enhance oxidative
      damage to DNA components in the presence of free iron ions and H(2)O(2).

PMID- 16107321
TI  - Formation of novel secondary metabolites by bacterial multimodular assembly
      lines: deviations from textbook biosynthetic logic.
AB  - Microorganisms produce an immense variety of natural products with useful
      biological activities. These compounds are often biosynthesized by
      multifunctional megasynthetases known as polyketide synthases and nonribosomal
      peptide synthetases. Recent literature on these natural product assembly lines
      suggests that they have a much greater mechanistic diversity than originally
      anticipated.

PMID- 16107322
TI  - Hepatoprotective mechanisms of Yan-gan-wan.
AB  - BACKGROUND AND AIMS: : A herbal prescription, Yan-gan-wan (YGW), has been known
      to offer hepatoprotective effects in Asian countries for years. This study
      investigated its mechanisms of action. METHODS: : The effects of YGW on CCl(4)
      induced liver damage were tested in mice and cultured hepatocytes. Microarray
      analysis screened genes affected by YGW. YGWs effects on the expression of
      cytochrome P450 (CYP) 2E1 and other isozymes were determined. YGWs effects on
      TNFalpha expression and NF-kappaB activation in Kupffer cells (KC), and TNFalpha
      promoter activity in RAW264.7 cells, were also assessed. RESULTS: :
      Administration of YGW reduced the plasma ALT, centrilobular necrosis,
      neutrophilic infiltration, and TNFalpha mRNA in the livers of mice acutely given
      CCl(4). The in vivo herb treatment reduced ALT release and necrosis of isolated
      hepatocytes directly exposed to CCl(4). Microarray analysis demonstrated marked
      reductions in CYP4A10 and 4A14 by YGW but no changes in other CYP isozymes as
      confirmed by immunoblot analysis. The herb treatment suppressed LPS-stimulated
      TNFalpha release in vivo and by cultured KC. Direct addition of the aqueous herb
      extract suppressed NF-kappaB activation by KC and TNFalpha promoter activity in
      RAW cells under LPS stimulation. This activity to suppress TNFalpha expression
      was largely separated into gel filtration fractions with the molecular size of
      102-107Da. YGW also attenuated liver fibrosis induced by chronic treatment of
      CCl(4) or porcine serum. CONCLUSIONS: : The protective effects of YGW on CCl(4)
      hepatotoxicity are due in part to inhibition of KC NF-kappaB activation and
      TNFalpha expression by small water soluble molecules, and may also be related to
      suppressed hepatic expression of CYP4A10 and 4A14 that are considered as
      alternative prooxidant cytochromes.

PMID- 16107323
TI  - An isoform shift in the cardiac adenine nucleotide translocase expression alters
      the kinetic properties of the carrier in dilated cardiomyopathy.
AB  - BACKGROUND: Impaired mitochondrial ADP/ATP transport and altered adenine
      nucleotide translocase (ANT) isoform expression characterized by enhanced ANT1
      and decreased ANT2 expression have been implicated in the pathophysiology of
      dilated cardiomyopathy (DCM). It is still unknown whether restricted ANT function
      results from exogenous factors, or mutations in the ANT genes, or whether the
      imbalance in the isoform composition causes the reduced ADP/ATP transport. We
      performed DNA mutation screening of ANT genes and analyzed the kinetic properties
      of ANT protein isolated from DCM hearts and controls in a reconstituted system
      excluding natural environmental influences. RESULTS: A G1409T polymorphism in
      ANT2 leads to an exchange from Arg111 to Leu111 in healthy blood donors (n = 60)
      with allele frequencies of 76% and 24%. This polymorphism was neither associated
      with DCM (74%, 26%; n = 93) nor with altered myocardial ANT isoform expression or
      restricted ANT function (89%, 11%; n = 8). However, there was a remarkable
      reduction in the maximum transport activity (v(max)) of reconstituted ANT from
      DCM hearts with altered ANT isoform expression (498 +/- 113 micromol min(-1) g(
      1) incorporated protein vs. 1112 +/- 178 micromol min(-1) g(-1) incorporated
      protein, p < 0.01). Moreover, the substrate affinity of DCM myocardial ANT to ATP
      was slightly reduced with an increased K(m) value of 104.3 +/- 2.4 microM vs.
      90.4 +/- 2.9 microM in controls (p < 0.03). CONCLUSION: The altered isoform
      expression in DCM hearts entails changes in the kinetic properties of total ANT
      protein restricting ANT function and contributing to disturbed energy metabolism
      in DCM.

PMID- 16107324
TI  - In vitro and in vivo enhancement of ganciclovir-mediated bystander cytotoxicity
      with gemcitabine.
AB  - To improve bystander cell killing with HSV-TK/GCV, we have utilized dFdCyd to
      reduce endogenous dGTP, which competes with GCVTP for incorporation into DNA. In
      this study we demonstrate the ability of dFdCyd to enhance GCV-mediated bystander
      cytotoxicity in cultured SW620 human colon carcinoma cells as well as in a murine
      xenograft model. In vitro, dFdCyd reduced cellular dGTP levels and produced a
      fourfold increase in the GCVTP:dGTP ratio. This elevated GCVTP:dGTP ratio
      resulted in a twofold increase in GCVMP incorporation into DNA in bystander cells
      cocultured with HSV-TK-expressing cells. The combination of GCV and dFdCyd was
      determined to be synergistic by isobologram analysis of bystander cytotoxicity.
      Tumors in mice treated with GCV and dFdCyd exhibited a significant growth delay
      requiring 40 days to obtain approximately 10 times their initial size compared to
      tumors in PBS- or single-drug-treated animals, which grew rapidly, increasing to
      a similar size in just 19 to 24 days. In addition, complete tumor regression was
      observed only in animals treated with both drugs. Furthermore, dFdCyd alone or in
      combination with GCV produced no evidence of toxicity or significant weight loss.
      These data suggest that dFdCyd may improve the clinical efficacy of HSV-TK/GCV
      gene therapies.

PMID- 16107325
TI  - mRNA expression of antioxidant enzymes (SOD, CAT and GSH-Px) and lipid
      peroxidative stress in liver of Atlantic salmon (Salmo salar) exposed to
      hyperoxic water during smoltification.
AB  - The mRNA levels of three antioxidant genes, Cu/Zn superoxide dismutase (SOD),
      catalase (CAT) and phospholipid hydroperoxide glutathione peroxidase (GSH-Px),
      were quantified with real-time qRT-PCR in liver of Atlantic salmon Salmo salar
      exposed to 80% (normoxia), 105% and 130% O2 saturation for 54 days. The salmon
      were then translocated and exposed to 90% and 130% O2 saturation for additional
      72 days during smoltification. TBARS and vitamin E levels in liver and the levels
      of oxidized glutathione (GSSG), total glutathione (GSH) and the resulting
      oxidative stress index (OSI) in blood were quantified as traditional oxidative
      stress markers. No significant mean normalized expression (MNE) differences of
      SOD, CAT or GSH-Px were found in liver after hyperoxia exposure at the two
      sampling times. Significantly decreased OSI was found in smolt exposed to 130% O2
      saturation after 126 days (n = 18, P < 0.0001), indicating hyperoxia-induced
      oxidative stress. No effects were seen on growth, or on the levels of
      thiobarbituric reactive substances (TBARS) and vitamin E in liver after the
      exposure experiment. Overall, the mRNA expression of SOD, CAT and GSH-Px in liver
      related poorly with the hyperoxic exposure regimes, and more knowledge are needed
      before the expressed levels of these antioxidant genes can be applied as
      biomarkers of hyperoxia in Atlantic salmon.

PMID- 16107326
TI  - Fibril modelling by sequence and structure conservation analysis combined with
      protein docking techniques: beta(2)-microglobulin amyloidosis.
AB  - Obtaining atomic resolution structural models of amyloid fibrils is currently
      impossible, yet crucial for our understanding of the amyloid mechanism. Different
      pathways in the transformation of a native globular domain to an amyloid fibril
      invariably involve domain destabilization. Hence, locating the unstable segments
      of a domain is important for understanding its amyloidogenic transformation and
      possibly control it. Since relative conservation is suggested to relate to local
      stability, we performed an extensive, sequence and structure conservation
      analysis of the beta(2)-microglobulin (beta(2)-m) domain. Our dataset include 51
      high resolution structures belonging to the "C1 set domain" family and 132
      clustered PSI-BLAST search results. Segments of the beta(2)-m domain
      corresponding to strands A (residues 12-18), D (45-55) and G (91-95) were found
      to be less conserved and stable, while the central strands B (residues 22-28), C
      (36-41), E (62-70) and F (78-83) were found conserved and stable. Our findings
      are supported by accumulating observations from various experimental methods,
      including urea denaturation, limited proteolysis, H/D exchange and structure
      determination by both NMR and X-ray crystallography. We used our conservation
      findings together with experimental literature information to suggest a
      structural model for the polymerized unit of beta(2)-m. Pairwise protein docking
      and subsequent monomer stacking in the same manner suggest a fibril model
      consistent with the cross-beta structure.

PMID- 16107327
TI  - Slowing down the Ras lane: miRNAs as tumor suppressors?
AB  - MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression
      by promoting the degradation of transcribed messages or by inhibiting
      translation. Although bioinformatic approaches suggest that miRNAs may regulate
      the expression of a large fraction of the genome, the determination of miRNA gene
      targets and biological functions has been comparatively limited. Emerging studies
      suggest that many miRNAs may participate in human disease, including oncogenesis;
      but for the most part, the observations have been correlative. A recent study by
      Johnson and colleagues indicates that the let-7 miRNA negatively regulates the
      oncogenic family of Ras guanosine triphosphatases in both Caenorhabditis elegans
      and human tumor cell lines, suggesting that let-7 may act as a tumor suppressor.
      This work raises several important questions: Can other miRNAs act as tumor
      suppressors or oncogenes? Is miRNA deregulation a critical aspect of tumor
      development and maintenance? A number of recent studies have begun to address
      some of these functional questions, providing the field with a greater
      understanding of the role of miRNAs in cancer.

PMID- 16107328
TI  - Teaching resources. Regulation of ion channels by G proteins.
AB  - This Teaching Resource provides lecture notes and slides for a class covering
      regulation of ion channels by G proteins and is part of the course "Cell
      Signaling Systems: A Course for Graduate Students." The lecture begins with an
      overview of calcium channels and then proceeds to describe the interaction of
      signaling molecules with calcium channels.

PMID- 16107329
TI  - The enigmatic acyl carrier protein phosphodiesterase of Escherichia coli: genetic
      and enzymological characterization.
AB  - The acyl carrier proteins (ACPs) of fatty acid synthesis are functional only when
      modified by attachment of the prosthetic group, 4'-phosphopantetheine (4'-PP),
      which is transferred from CoA to the hydroxyl group of a specific serine residue.
      Almost 40 years ago Vagelos and Larrabee reported an enzyme from Escherichia coli
      that removed the prosthetic group. We report that this enzyme, called ACP
      hydrolyase or ACP phosphodiesterase, is encoded by a gene (yajB) of previously
      unknown function that we have renamed acpH. A mutant E. coli strain having a
      total deletion of the acpH gene has been constructed that grows normally, showing
      that phosphodiesterase activity is not essential for growth, although it is
      required for turnover of the ACP prosthetic group in vivo. ACP phosphodiesterase
      (AcpH) has been purified to homogeneity for the first time and is a soluble
      protein that very readily aggregates upon overexpression in vivo or concentration
      in vitro. The purified enzyme has been shown to cleave acyl-ACP species with acyl
      chains of 6-16 carbon atoms and is active on some, but not all, non-native ACP
      species tested. Possible physiological roles for AcpH are discussed.

PMID- 16107330
TI  - Histidine-rich glycoprotein specifically binds to necrotic cells via its amino
      terminal domain and facilitates necrotic cell phagocytosis.
AB  - Cells that become necrotic or apoptotic through tissue damage or during normal
      cellular turnover are usually rapidly cleared from the circulation and tissues by
      phagocytic cells. A number of soluble proteins have been identified that
      facilitate the phagocytosis of apoptotic cells, but few proteins have been
      defined that selectively opsonize necrotic cells. Previous studies have shown
      that histidine-rich glycoprotein (HRG), an abundant (approximately 100 microg/ml)
      75-kDa plasma glycoprotein, binds to cell surface heparan sulfate on viable cells
      and cross-links other ligands, such as plasminogen, to the cell surface. In this
      study we have demonstrated that HRG also binds very strongly, in a heparan
      sulfate-independent manner, to cytoplasmic ligand(s) exposed in necrotic cells.
      This interaction is mediated by the amino-terminal domain of HRG and results in
      enhanced phagocytosis of the necrotic cells by a monocytic cell line. In
      contrast, it was found that HRG binds poorly to and does not opsonize early stage
      apoptotic cells. Thus, HRG has the unique property of selectively recognizing
      necrotic cells and may play an important physiological role in vivo by
      facilitating the uptake and clearance of necrotic, but not apoptotic, cells by
      phagocytes.

PMID- 16107331
TI  - Yeast Pex14p possesses two functionally distinct Pex5p and one Pex7p binding
      sites.
AB  - Current evidence favors a cycling receptor model for the import of peroxisomal
      matrix proteins. The yeast Pex14 protein together with Pex13p and Pex17p form the
      docking subcomplex at the peroxisomal membrane and interact in this cycle with
      both soluble import receptors Pex5p and Pex7p. In a first step of a structure
      function analysis of Saccharomyces cerevisiae Pex14p, we mapped its binding sites
      with both receptors. Using the yeast two-hybrid system and pull-down assays, we
      showed that Pex5p directly interacts with two separate regions of ScPex14p, amino
      acid residues 1-58 and 235-308. The latter binding site at the C terminus of
      ScPex14p overlaps with a binding site of Pex7p at amino acid residues 235-325.
      The functional assessment of these two binding sites of ScPex14p with the
      peroxisomal targeting signal receptors indicates that they have distinct roles.
      Deletion of the N-terminal 58 amino acids caused a partial defect of matrix
      protein import in pex14delta cells expressing the Pex14-(59-341)-p fragment;
      however, it did not lead to a pex phenotype. In contrast, truncation of the C
      terminal 106 amino acids of ScPex14p completely blocked this process. On the
      basis of these and other published data, we propose that the C terminus of Pex14p
      contains the actual docking site and discuss the possibility that the N terminus
      could be involved in a Pex5p-Pex14p association inside the peroxisomal membrane.

PMID- 16107332
TI  - Inactivation of organellar glutamyl- and seryl-tRNA synthetases leads to
      developmental arrest of chloroplasts and mitochondria in higher plants.
AB  - Aminoacyl-tRNA synthetases (ARSs) are key enzymes involved in protein
      translation, and both cytosolic and organellar forms are present in the genomes
      of eukaryotes. In this study, we investigated cellular effects of depletion of
      organellar forms of ARS using virus-induced gene silencing (VIGS) in Nicotiana
      benthamiana. VIGS of NbERS and NbSRS, which encode organellar GluRS and SerRS,
      respectively, resulted in a severe leaf-yellowing phenotype. The NbERS and NbSRS
      genes were ubiquitously expressed in plant tissues, and induced in response to
      light. Green fluorescent protein (GFP) fusion proteins of the full-length
      glutamyl-tRNA synthetase (ERS) and seryl-tRNA synthetase (SRS) of Arabidopsis and
      GFP fusions to the N-terminal extension of these proteins were all dualtargeted
      to chloroplasts and mitochondria. At the cell level, depletion of NbERS and NbSRS
      resulted in dramatically reduced numbers of chloroplasts with reduced sizes and
      chlorophyll content. The numbers and/or physiology of mitochondria were also
      severely affected. The abnormal chloroplasts lacked most of the thylakoid
      membranes and appeared to be degenerating, whereas some of them showed doublet
      morphology, indicating defective chloroplast division. Pulse-field gel
      electrophoresis analyses demonstrated that chloroplast DNA in subgenomic sizes is
      the predominant form in the abnormal chloroplasts. Interestingly, despite severe
      abnormalities in chloroplasts and mitochondria, expression of many nuclear genes
      encoding chloroplastor mitochondria-targeted proteins, and chlorophyll
      biosynthesis genes remained unchanged in the ERS and SRS VIGS lines. This is the
      first report to analyze the effect of ARS disruption on organelle development in
      plants.

PMID- 16107333
TI  - The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1
      in T lymphocytes.
AB  - Combined phylogenetic and chromosomal location studies suggest that the orphan
      receptor RDC1 is related to CXC chemokine receptors. RDC1 provides a co-receptor
      function for a restricted number of human immunodeficiency virus (HIV) isolates,
      in particular for the CXCR4-using HIV-2 ROD strain. Here we show that CXCL12, the
      only known natural ligand for CXCR4, binds to and signals through RDC1. We
      demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12-promoted
      chemotaxis is inhibited by an anti-RDC1 monoclonal antibody. Concomitant blockade
      of RDC1 and CXCR4 produced additive inhibitory effects in CXCL12-induced T cell
      migration. Furthermore, we provide evidence that interaction of CXCL12 with RDC1
      is specific, saturable, and of high affinity (apparent KD approximately 0.4 nM).
      In CXCR4-negative cells expressing RDC1, CXCL12 promotes internalization of the
      receptor and chemotactic signals through RDC1. Collectively, our data indicate
      that RDC1, which we propose to rename as CXCR7, is a receptor for CXCL12.

PMID- 16107334
TI  - Synthesis of anticoagulantly active heparan sulfate proteoglycans by glomerular
      epithelial cells involves multiple 3-O-sulfotransferase isoforms and a limiting
      precursor pool.
AB  - Endothelial and other select cell types synthesize a subpopulation of heparan
      sulfate (HS) proteoglycans (HSPGs), anticoagulant HSPGs (aHSPGs) that bear aHS-HS
      chains with the cognate 3-O-sulfated pentasaccharide motif that can bind and
      activate anti-thrombin (AT). Endothelial cells regulate aHSPG production by
      limiting levels of HS 3-O-sulfotransferase-1 (3-OST-1), which modifies a non
      limiting pool of aHS-precursors. By probing kidney cryosections with (125)I-AT
      and fluorescently tagged AT we found that the glomerular basement membrane
      contains aHSPGs, with the staining pattern implicating synthesis by glomerular
      epithelial cells (GECs). Indeed, cultured GECs synthesized aHS with high AT
      affinity that was comparable with the endothelial product. Disaccharide analyses
      of human GEC (hGEC) HS in conjunction with transcript analyses revealed that
      hGECs express predominantly 3-OST-1 and 3-OST-3(A). aHS production has not been
      previously examined in cells expressing multiple 3-OST isoforms. This unusual
      situation appears to involve novel mechanisms to regulate aHS production, as HS
      structural analyses suggest hGECs exhibit excess levels of 3-OST-1 and an
      extremely limiting pool of aHS-precursor. A limiting aHS-precursor pool may serve
      to minimize aHS synthesis by non-3-OST-1 isoforms. Indeed, we show that high in
      vitro levels of 3-OST-3(A) can efficiently generate aHS. Non-3-OST-1 isoforms can
      generate aHS in vivo, as the probing of kidney sections from 3-OST-1-deficient
      mice revealed GEC synthesis of aHSPGs. Surprisingly, Hs3st1(-/-) kidney only
      expresses 3-OST isoforms having a low specificity for aHS synthesis. Thus, our
      analyses reveal a cell type that expresses multiple 3-OST isoforms and produces
      minimal amounts of aHS-precursor. In part, this mechanism should prevent aHS
      overproduction by non-3-OST-1 isoforms. Such a role may be essential, as 3-OST
      isoforms that have a low specificity for aHS synthesis can generate substantial
      levels of aHSPGs in vivo.

PMID- 16107335
TI  - Development of zinc finger domains for recognition of the 5'-CNN-3' family DNA
      sequences and their use in the construction of artificial transcription factors.
AB  - Considerable progress has been made in recent years in the design of
      transcription factors for the directed regulation of endogenous genes. Although
      many strategies involve selection methods that must be applied for each new
      target sequence, we have developed an approach based on linkage of predefined
      zinc finger domains that each recognize a three-base pair DNA sequence to
      construct artificial transcription factors that bind to a desired sequence. These
      domains can be assembled to recognize unique 18-base pair DNA sequences with high
      specificity. Here we report the development and characterization of zinc finger
      domains that bind to 15 of the 16 5'-CNN-3' subsites. These domains were created
      through a combination of phage display selection, site-directed mutagenesis, and
      de novo design. Furthermore, these domains were used to generate a highly
      specific six-finger protein targeting the ERBB-2 promoter. When fused to
      regulatory domains, this protein was capable of up- and down-regulating the
      expression of the endogenous ERBB-2 gene. With the addition of this collection of
      predefined zinc finger domains, most 5'-CNN-3'-, 5'-GNN-3'-, and 5'-ANN-3'
      containing sequences can now be rapidly targeted for directed gene regulation and
      nuclease cleavage.

PMID- 16107336
TI  - Tumor necrosis factor alpha (TNFalpha) induces the unfolded protein response
      (UPR) in a reactive oxygen species (ROS)-dependent fashion, and the UPR
      counteracts ROS accumulation by TNFalpha.
AB  - Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes ER
      overload, resulting in ER stress. To cope with ER stress, mammalian cells trigger
      a specific response known as the unfolded protein response (UPR). Although recent
      studies have indicated cross-talk between ER stress and oxidative stress, the
      mechanistic link is not fully understood. By using murine fibrosarcoma L929
      cells, in which tumor necrosis factor (TNF) alpha induces accumulation of
      reactive oxygen species (ROS) and cell death, we show that TNFalpha induces the
      UPR in a ROS-dependent fashion. In contrast to TNFalpha, oxidative stresses by
      H2O2 or arsenite only induce eukaroytic initiation factor 2alpha phosphorylation,
      but not activation of PERK- or IRE1-dependent pathways, indicating the
      specificity of downstream signaling induced by various oxidative stresses.
      Conversely, the UPR induced by tunicamycin substantially suppresses TNFalpha
      induced ROS accumulation and cell death by inhibiting reduction of cellular
      glutathione levels. Collectively, some, but not all, oxidative stresses induce
      the UPR, and pre-emptive UPR counteracts TNFalpha-induced ROS accumulation.

PMID- 16107337
TI  - Post-translational regulation of mercaptopyruvate sulfurtransferase via a low
      redox potential cysteine-sulfenate in the maintenance of redox homeostasis.
AB  - 3-Mercaptopyruvate sulfurtransferase (MST) (EC 2.8.1.2), a multifunctional
      enzyme, catalyzes a transsulfuration from mercaptopyruvate to pyruvate in the
      degradation process of cysteine. A stoichiometric concentration of hydrogen
      peroxide and of tetrathionate (S(4)O(6)(2-)) inhibited rat MST (k(i) = 3.3 min(
      1), K(i) = 120.5 microM and k(i) = 2.5 min(-1), K(i) = 178.6 microM,
      respectively). The activity was completely restored by dithiothreitol or
      thioredoxin with a reducing system containing thioredoxin reductase and NADPH,
      but glutathione did not restore the activity. On the other hand, an excess molar
      ratio dose of hydrogen peroxide inactivated MST. Oxidation with a stoichiometric
      concentration of hydrogen peroxide protected the enzyme against reaction by
      iodoacetate, which modifies a catalytic Cys(247), suggesting that Cys(247) is a
      target of the oxidants. A matrix-assisted laser desorption/ionization-time-of
      flight mass spectrometric analysis revealed that hydrogen peroxide- and
      tetrathionate-inhibited MSTs were increased in molecular mass consistent with the
      addition of atomic oxygen and with a thiosulfate (S(2)O(3)(-)), respectively.
      Treatment with dithiothreitol restored modified MST to the original mass. These
      findings suggested that there was no nearby cysteine with which to form a
      disulfide, and mild oxidation of MST resulted in formation of a sulfenate (SO(-))
      at Cys(247), which exhibited exceptional stability and a lower redox potential
      than that of glutathione. Oxidative stress decreases MST activity so as to
      increase the amount of cysteine, a precursor of thioredoxin or glutathione, and
      furthermore, these cellular reductants restore the activity. Thus the redox state
      regulates MST activity at the enzymatic level, and on the other hand, MST
      controls redox to maintain cellular redox homeostasis.

PMID- 16107338
TI  - Anthocyanins induce cholesterol efflux from mouse peritoneal macrophages: the
      role of the peroxisome proliferator-activated receptor {gamma}-liver X receptor
      {alpha}-ABCA1 pathway.
AB  - It is widely accepted that stimulation of reverse cholesterol transport, the
      efflux of excess cholesterol from peripheral tissues and transferring it to the
      liver for biliary excretion, is becoming an important component in reducing
      excess cholesterol deposition in atherosclerotic plaques. The ATP-binding
      cassette transporter has been identified as a key regulator of macrophage
      cholesterol efflux and apoAI-mediated reverse cholesterol transport. In vivo
      studies have documented anthocyanins, a large group of naturally phenolic
      compounds rich in plants, possess substantial capacities in improving plasma
      cholesterol levels. In this study, we investigated the potential role of
      anthocyanins in modulating cholesterol efflux from mouse peritoneal macrophages
      and macrophage-derived foam cells and the possible molecular mechanism linking
      ABCA1 to cholesterol efflux. Incubation of the mouse peritoneal macrophages and
      macrophage-derived foam cells with cyanidin-3-O-beta-glucoside and peonidin-3-O
      beta-glucoside led to dose-dependent (1-100 microM) induction in cholesterol
      efflux and ABCA1 mRNA expression, and this effect could be blocked by the ABCA1
      inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, disodium salt, and
      a general inhibitor of gene transcription actinomycin D. Treatment of the
      macrophages with anthocyanins also activated peroxisome proliferator-activated
      receptor gamma, liver X receptor alpha mRNA expression, and their mediated gene
      expression. Addition of geranylgeranyl pyrophosphate ammonium salt or GW9662
      markedly inhibited the anthocyanin-induced increase of ABCA1 gene expression and
      apoAI-mediated cholesterol efflux. These data demonstrated that anthocyanin
      induces cholesterol efflux from mouse peritoneal macrophages and macrophage
      derived foam cells and that stimulation of cholesterol efflux by anthocyanin is
      mediated, at least in part, by peroxisome proliferator-activated receptor gamma
      liver X receptor alpha-ABCA1 signaling pathway activation.

PMID- 16107339
TI  - Elucidating the role of H/ACA-like RNAs in trans-splicing and rRNA processing via
      RNA interference silencing of the Trypanosoma brucei CBF5 pseudouridine synthase.
AB  - Most pseudouridinylation in eukaryotic rRNA and small nuclear RNAs is guided by
      H/ACA small nucleolar RNAs. In this study, the Trypanosoma brucei pseudouridine
      synthase, Cbf5p, a snoRNP protein, was identified and silenced by RNAi. Depletion
      of this protein destabilized all small nucleolar RNAs of the H/ACA-like family.
      Following silencing, defects in rRNA processing, such as accumulation of
      precursors and inhibition of cleavages to generate the mature rRNA, were
      observed. snR30, an H/ACA RNA involved in rRNA maturation, was identified based
      on prototypical conserved domains characteristic of this RNA in other eukaryotes.
      The silencing of CBF5 also eliminated the spliced leader-associated (SLA1) RNA
      that directs pseudouridylation on the spliced leader RNA (SL RNA), which is the
      substrate for the trans-splicing reaction. Surprisingly, the depletion of Cbf5p
      not only eliminated the pseudouridine on the SL RNA but also abolished capping at
      the fourth cap-4 nucleotide. As a result of defects in the SL RNA and decreased
      modification on the U small nuclear RNA, trans-splicing was inhibited at the
      first step of the reaction, providing evidence for the essential role of H/ACA
      RNAs and the modifications they guide on trans-splicing.

PMID- 16107340
TI  - The Q-loop disengages from the first intracellular loop during the catalytic
      cycle of the multidrug ABC transporter BmrA.
AB  - The ATP-binding cassette is the most abundant family of transporters including
      many medically relevant members and gathers both importers and exporters involved
      in the transport of a wide variety of substrates. Although three high resolution
      three-dimensional structures have been obtained for a prototypic exporter, MsbA,
      two have been subjected to much criticism. Here, conformational changes of BmrA,
      a multidrug bacterial transporter structurally related to MsbA, have been
      studied. A three-dimensional model of BmrA, based on the "open" conformation of
      Escherichia coli MsbA, was probed by simultaneously introducing two cysteine
      residues, one in the first intracellular loop of the transmembrane domain and the
      other in the Q-loop of the nucleotide-binding domain (NBD). Intramolecular
      disulfide bonds could be created in the absence of any effectors, which prevented
      both drug transport and ATPase activity. Interestingly, addition of ATP/Mg plus
      vanadate strongly prevented this bond formation in a cysteine double mutant,
      whereas ATP/Mg alone was sufficient when the ATPase-inactive E504Q mutation was
      also introduced, in agreement with additional BmrA models where the ATP-binding
      sites are positioned at the NBD/NBD interface. Furthermore, cross-linking between
      the two cysteine residues could still be achieved in the presence of ATP/Mg plus
      vanadate when homobifunctional cross-linkers separated by more than 13 Angstrom
      were added. Altogether, these results give support to the existence, in the
      resting state, of a monomeric conformation of BmrA similar to that found within
      the open MsbA dimer and show that a large motion is required between
      intracellular loop 1 and the nucleotide-binding domain for the proper functioning
      of a multidrug ATP-binding cassette transporter.

PMID- 16107341
TI  - Modification of the Stat1 SH2 domain broadly improves interferon efficacy in
      proportion to p300/CREB-binding protein coactivator recruitment.
AB  - A normal level of interferon (IFN) responsiveness via the Stat1 transcription
      factor is critical to the host, since decreased Stat1 signaling causes immune
      compromise and increased signaling is associated with inflammatory and neoplastic
      disease. Here we report how this balance may be influenced by novel alterations
      in the efficiency of Stat1 signaling. To enable disulfide-dependent and
      spontaneous formation of active Stat1 homodimer (as was done previously for
      Stat3), we engineered Stat1-CC with double-cysteine substitutions in the Src
      homology 2 (SH2)-homodimerization domain (at Ala-656 and Asn-658). In this case,
      however, mutant and wild-type Stat1 exhibited no difference
      inspontaneousdimerization. Moreover, Stat1-CC still required ligand-dependent Tyr
      701 phosphorylation for function and exhibited hyperresponsiveness to IFN-beta
      (that depends on Stat1/Stat2 heterodimerization) as well as IFN-gamma (that
      depends on Stat1/Stat1 homodimerization). Hyperresponsivenss of Stat1-CC was
      accompanied by increased capacities for Tyr-701 phosphorylation and DNA binding,
      but these features were also found in a similarly substituted serine mutant
      (Stat1-SS) that showed no hyperresponsiveness to IFN-gamma. This finding raised
      the possibility that SH2 domain mutations also influence downstream
      transcriptional efficiency. Indeed, each of these mutations also enhanced
      recruitment of the normally rate-limiting p300/CREB-binding Protein (CBP)
      coactivator to the transcriptional complex in proportion to the level of IFN
      driven transactivation and gene expression. Additional modifications indicated
      that the mutant residues in the SH2 domain appeared to cooperate with Ser-727 in
      the C-terminal domain to regulate p300/CBP interaction with Stat1. The profile of
      IFN responsiveness translated into the same progressive increase in the level of
      viral clearance from Stat1- to Stat1-SS- to Stat1-CC-expressing cells. Thus, SH2
      domain determinants may be modified to direct better Stat1 phosphorylation, DNA
      binding, and coactivator recruitment to fully improve IFN efficacy.

PMID- 16107342
TI  - Cooperative phosphorylation of the tumor suppressor phosphatase and tensin
      homologue (PTEN) by casein kinases and glycogen synthase kinase 3beta.
AB  - The phosphatase and tensin homologue (PTEN) tumor suppressor is a
      phosphatidylinositol D3-phosphatase that counteracts the effects of
      phosphatidylinositol 3-kinase and negatively regulates cell growth and survival.
      PTEN is itself regulated by phosphorylation on multiple serine and threonine
      residues in its C terminus. Previous work has implicated casein kinase 2 (CK2) as
      the kinase responsible for this phosphorylation. Here we showed that CK2 does not
      phosphorylate all sites in PTEN and that glycogen synthase kinase 3beta
      (GSK3beta) also participates in PTEN phosphorylation. Although CK2 mainly
      phosphorylated PTEN at Ser-370 and Ser-385, GSK3beta phosphorylated Ser-362 and
      Thr-366. More importantly, prior phosphorylation of PTEN at Ser-370 by CK2
      strongly increased its phosphorylation at Thr-366 by GSK3beta, suggesting that
      the two may synergize. Using RNA interference, we showed that GSK3 phosphorylates
      PTEN in intact cells. Finally, PTEN phosphorylation was affected by insulin-like
      growth factor in intact cells. We concluded that multiple kinases, including CK2
      and GSK3beta, participate in PTEN phosphorylation and that GSK3beta may provide
      feedback regulation of PTEN.

PMID- 16107343
TI  - Identification of intra- and intermolecular disulfide bridges in the multidrug
      resistance transporter ABCG2.
AB  - ABCG2 is an ATP binding cassette (ABC) half-transporter that plays a key role in
      multidrug resistance to chemotherapy. ABCG2 is believed to be a functional
      homodimer that has been proposed to be linked by disulfide bridges. We have
      investigated the structural and functional role of the only three cysteines
      predicted to be on the extracellular face of ABCG2. Upon mutation of Cys-592 or
      Cys-608 to alanine (C592A and C608A), ABCG2 migrated as a dimer in SDS-PAGE under
      non-reducing conditions; however, mutation of Cys-603 to Ala (C603A) caused the
      transporter to migrate as a single monomeric band. Despite this change, C603A
      displayed efficient membrane targeting and preserved transport function. Because
      the transporter migrated as a dimer in SDS-PAGE, when only Cys-603 was present
      (C592A-C608A), the data suggest that Cys-603 forms a symmetrical intermolecular
      disulfide bridge in the ABCG2 homodimer that is not essential for protein
      expression and function. In contrast to C603A, both C592A and C608A displayed
      impaired membrane targeting and function. Moreover, when only Cys-592 or Cys-608
      were present (C592A/C603A and C603A/C608A), the transporter displayed impaired
      plasma membrane expression and function. The combined mutation (C592A/C608A)
      partially restored plasma membrane expression; however, although transport of
      mitoxantrone was almost normal, we observed impairment of BODIPY-prazosin
      transport. This supports the conclusion that Cys-592 and Cys-608 form an
      intramolecular disulfide bridge in ABCG2 that is critical for substrate
      specificity. Finally, mutation of all three cysteines simultaneously resulted in
      low expression and no measurable function. Altogether, our data are consistent
      with a scenario in which an inter- and an intramolecular disulfide bridge
      together are of fundamental importance for the structural and functional
      integrity of ABCG2.

PMID- 16107344
TI  - White matter hyperintensities: a target for the prevention of cognitive decline?

PMID- 16107345
TI  - "Patients' choice".

PMID- 16107346
TI  - STN stimulation and neuroprotection in Parkinson's disease--when beautiful
      theories meet ugly facts.

PMID- 16107347
TI  - DWI and acute stroke prognosis: a simple approach.

PMID- 16107348
TI  - The effect of deep brain stimulation on quality of life in movement disorders.
AB  - Deep brain stimulation (DBS) is a viable treatment alternative for patients with
      Parkinson's disease (PD), essential tremor (ET), dystonia, and cerebellar outflow
      tremors. When poorly controlled, these disorders have detrimental effects on the
      patient's health related quality of life (HRQoL). Instruments that measure HRQoL
      are useful tools to assess burden of disease and the impact of therapeutic
      interventions on activities of daily living, employment, and other functions. We
      systematically and critically reviewed the literature on the effects of DBS on
      HRQoL in PD, ET, dystonia, and cerebellar outflow tremor related to multiple
      sclerosis.

PMID- 16107349
TI  - Amyloid mediates the association of apolipoprotein E e4 allele to cognitive
      function in older people.
AB  - BACKGROUND: The neurobiological changes underlying the association of the
      apolipoprotein E (APOE) e4 allele with level of cognition are poorly understood.
      OBJECTIVE: To test the hypothesis that amyloid load can account for (mediate) the
      association of the APOE e4 allele with level of cognition assessed proximate to
      death. METHODS: There were 44 subjects with clinically diagnosed Alzheimer's
      disease and 50 without dementia, who had participated in the Religious Orders
      Study. They underwent determination of APOE allele status, had comprehensive
      cognitive testing in the last year of life, and brain autopsy at death. The
      percentage area of cortex occupied by amyloid beta and the density of tau
      positive neurofibrillary tangles were quantified from six brain regions and
      averaged to yield summary measures of amyloid load and neurofibrillary tangles.
      Multiple regression analyses were used to examine whether amyloid load could
      account for the effect of allele status on level of cognition, controlling for
      age, sex, and education. RESULTS: Possession of at least one APOE e4 allele was
      associated with lower level of cognitive function proximate to death (p = 0.04).
      The effect of the e4 allele was reduced by nearly 60% and was no longer
      significant after controlling for the effect of amyloid load, whereas there was a
      robust inverse association between amyloid and cognition (p = 0.001). Because
      prior work had suggested that neurofibrillary tangles could account for the
      association of amyloid on cognition, we next examined whether amyloid could
      account for the effect of allele status on tangles. In a series of regression
      analyses, e4 was associated with density of tangles (p = 0.002), but the effect
      of the e4 allele was reduced by more than 50% and was no longer significant after
      controlling for the effect of amyloid load. CONCLUSION: These findings are
      consistent with a sequence of events whereby the e4 allele works through amyloid
      deposition and subsequent tangle formation to cause cognitive impairment.

PMID- 16107350
TI  - Thrombus in transit through a patent foramen ovale: paradoxical embolism.

PMID- 16107351
TI  - The role of levodopa in the management of dementia with Lewy bodies.
AB  - BACKGROUND: One of the core clinical features of dementia with Lewy bodies (DLB)
      is extrapyramidal syndrome (EPS). Levodopa is currently the gold standard oral
      therapy for Parkinson's disease (PD), but its use in DLB has been tempered by
      concerns of exacerbating neuropsychiatric symptoms. AIM: To assess the efficacy
      and tolerability of L-dopa in managing EPS in DLB and to compare the motor
      response with that seen in PD and PD with dementia (PDD). METHOD: EPS assessment
      consisted of the Unified Parkinson's Disease Rating Scale, motor subsection
      (UPDRS III), and finger tapping and walking tests. Patients with DLB were
      commenced on L-dopa. After 6 months, patients were examined in the "off" state,
      given L-dopa and assessed for motor responses. Identical assessments were
      performed in patients with PD and PDD also receiving L-dopa. RESULTS: Acute L
      dopa challenge in 14 DLB patients yielded a mean 13.8% (p = 0.02) improvement in
      UPDRS III score, compared with 20.5% in PD (n = 28, p < 0.0001) and 23% in PDD (n
      = 30, p<0.0001) respectively. Finger tapping scores increased (12.3% v 20% and
      23%), while walking test scores decreased (32% v 41% and 67%). Of the DLB
      patients, 36% were classified as "responders" on L-dopa challenge, compared with
      70% of the PDD and 57% of the PD patients. Nineteen DLB patients were treated for
      6 months with L-dopa (mean daily dose 323 mg). Two withdrew prematurely with
      gastrointestinal symptoms and two with worsening confusion. CONCLUSION: L-dopa
      was generally well tolerated in DLB but produced a significant motor response in
      only about one third of patients. Younger DLB cases were more likely to respond
      to dopaminergic treatment.

PMID- 16107352
TI  - Lateralisation of striatal function: evidence from 18F-dopa PET in Parkinson's
      disease.
AB  - OBJECTIVES: The aetiology of the cognitive changes seen in Parkinson's disease
      (PD) is multifactorial but it is likely that a significant contribution arises
      from the disruption of dopaminergic pathways. This study aimed to investigate the
      contribution of the dopaminergic system to performance on two executive tasks
      using (18)F-6-fluorodopa positron emission tomography ((18)F-dopa PET) in PD
      subjects with early cognitive changes. METHODS: 16 non-demented, non-depressed PD
      subjects were evaluated with the Tower of London (TOL) spatial planning task, a
      verbal working memory task (VWMT) and (18)F-dopa PET, all known to be affected in
      early PD. Statistical parametric mapping (SPM) localised brain regions in which
      (18)F-dopa uptake covaried with performance scores. Frontal cortical resting
      glucose metabolism was assessed with (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG)
      PET. RESULTS: SPM localised significant covariation between right caudate (18)F
      dopa uptake (Ki) and TOL scores and between left anterior putamen Ki and VWMT
      performance. No significant covariation was found between task scores and (18)F
      dopa Ki values in either limbic or cortical regions. Frontal cortical glucose
      metabolism was preserved in all cases. CONCLUSIONS: These findings support a
      causative role of striatal dopaminergic depletion in the early impairment of
      executive functions seen in PD. They suggest that spatial and verbal executive
      tasks require integrity of the right and left striatum, respectively, and imply
      that the pattern of cognitive changes manifest by a patient with PD may reflect
      differential dopamine loss in the two striatal complexes.

PMID- 16107353
TI  - How useful is [123I]beta-CIT SPECT in clinical practice?
AB  - OBJECTIVE: To assess the accuracy and clinical usefulness of [(123)I]beta-CIT
      (2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) SPECT in the differential
      diagnosis of Parkinson's disease. SUBJECTS: 185 consecutive patients with
      symptoms of movement disorder were studied. The diagnoses were Parkinson's
      disease (92), essential tremor (16), vascular parkinsonism (15), various
      Parkinson plus syndromes (P+) (12), dementia with Lewy bodies (DLB) (5), dystonia
      (5), drug induced movement disorder (12), and other diagnoses (8). A reference
      group (psychogenic parkinsonism) comprised 20 subjects with complaints suggesting
      extrapyramidal disease but with no unequivocal signs on clinical examination and
      no abnormalities on brain imaging. RESULTS: beta-CIT uptake was significantly
      lower in the whole striatum as well as separately in the putamen and in the
      caudate nucleus in Parkinson's disease than in the reference group or in drug
      induced movement disorder, essential tremor, or dystonia. The uptake of beta-CIT
      in the vascular parkinsonism group was heterogeneous and mean beta-CIT uptake
      fell between the reference group and the Parkinson's disease group. In the P+ and
      DLB groups the striatal uptake ratios overlapped those of the Parkinson's disease
      group. CONCLUSIONS: [(123)I]beta-CIT SPECT may not be as useful a tool in the
      clinical differential diagnosis of Parkinson's disease as was previously
      believed, but it was 100% sensitive and specific for the diagnosis in younger
      patients (age <55 years). In older patients (age >55 years) specificity was
      substantially lower (68.5%). This differential specificity reflected the
      different distribution of differential diagnostic disorders (P+, DLB, vascular
      parkinsonism) in the older and younger age groups.

PMID- 16107354
TI  - Disease progression continues in patients with advanced Parkinson's disease and
      effective subthalamic nucleus stimulation.
AB  - OBJECTIVES: Glutamate mediated excitotoxicity of the hyperactive subthalamic
      nucleus (STN) has been reported to contribute to nigral degeneration in
      Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its
      role as a highly effective treatment of severe PD motor complications, has been
      thought to inhibit STN hyperactivity and therefore decrease progression of PD.
      METHODS: In a prospective two centre study, disease progression was determined by
      means of serial (18)F-fluorodopa (F-dopa) positron emission tomography (PET) in
      30 patients with successful STN DBS over the first 16 (SD 6) months after
      surgery. RESULTS: Depending on the method of PET data analysis used in the two
      centres, annual progression rates relative to baseline were 9.5-12.4% in the
      caudate and 10.7-12.9% in the putamen. CONCLUSIONS: This functional imaging study
      is the first to demonstrate a continuous decline of dopaminergic function in
      patients with advanced PD under clinically effective bilateral STN stimulation.
      The rates of progression in patients with STN DBS were within the range of
      previously reported data from longitudinal imaging studies in PD. Therefore this
      study could not confirm the neuroprotective properties of DBS in the STN target.

PMID- 16107355
TI  - Specific DWI lesion patterns predict prognosis after acute ischaemic stroke
      within the MCA territory.
AB  - BACKGROUND: Apart from diffusion-weighted imaging (DWI) lesion volume and
      diffusion-perfusion mismatching, there is limited information about
      neuroradiological predictors of early prognosis after an ischaemic stroke. This
      study sought to identify specific DWI lesion patterns that would help prediction
      of early prognosis of three different endpoints: unstable hospital course,
      recurrence of stroke, and poor neurological outcome at 90 days after ischaemic
      stroke. METHODS: A total of 426 patients with acute cerebral infarcts within the
      middle cerebral artery territory were prospectively studied. Using the DWI data
      the patients were divided into six groups (territorial, other cortical, small
      superficial, internal border zone, small deep, and other deep infarcts), and any
      recurrent strokes and prognosis over the following 90 days were recorded.
      RESULTS: DWI lesion pattern was a stronger and more consistent independent
      outcome predictor than DWI lesion volume. The specific DWI lesion patterns
      associated with each endpoint differed. An unstable hospital course was
      frequently observed in patients with internal border zone infarcts, whereas
      recurrent strokes after the index stroke were commoner in those who had small
      superficial infarcts (p<0.05 in both cases). Similarly, poor outcome after stroke
      was associated with older age, severe neurological deficits at admission, and a
      DWI lesion pattern showing internal border zone infarcts. CONCLUSIONS: The
      results of the present study indicate that the DWI lesion pattern may help in
      recognition of the likely differences in the early prognostic endpoints after
      ischaemic stroke, and DWI analysis may guide targeted interventions to prevent
      negative outcomes.

PMID- 16107356
TI  - White matter hyperintensities as a predictor of neuropsychological deficits post
      stroke.
AB  - OBJECTIVES: Cerebral white matter hyperintensities (WMHs) on magnetic resonance
      imaging (MRI) are a recognised risk factor for post-stroke dementia. Their
      specific relations to cognitive impairment are still not well known. The purpose
      of this study was to explore how the severity and location of WMHs predict
      neuropsychological test performance in the context of other brain lesions in
      elderly stroke patients. METHODS: In the Helsinki Stroke Aging Memory Study, 323
      patients, aged from 55 to 85 years, completed a detailed neuropsychological test
      battery and MRI 3 months after an ischaemic stroke. The demographic and MRI
      predictors of cognition were studied with sequential linear regression analyses.
      RESULTS: After age, education and total infarct volume were controlled for, the
      overall degree of WMHs predicted poor performance in tests of mental speed,
      executive functions, memory, and visuospatial functions, but not in those of
      short term memory storage or verbal conceptualisation. However, the contribution
      of separate white matter regions was relatively low. Only the lesions along the
      bodies of lateral ventricles were independently associated with speed and
      executive measures. Additionally, general cortical atrophy clearly predicted a
      wide range of cognitive deficits while infarct volume had less relevance. Further
      analyses revealed that executive functions act as a strong mediator between the
      relationship of WMHs to memory and visuospatial functions. CONCLUSIONS: The
      degree of WMHs is independently related to post-stroke cognitive decline. The
      most affected cognitive domains seem to be executive functions and speed of
      mental processing, which may lead to secondary deficits of memory and
      visuospatial functions.

PMID- 16107357
TI  - Intravenous rt-PA for acute stroke: comparing its effectiveness in younger and
      older patients.
AB  - OBJECTIVE: To study the short and long term differences in outcome between
      patients > or =80 years of age and those < or =79 years of age who received
      intravenous recombinant tissue plasminogen activator (iv rt-PA) for acute stroke
      within the first 3 hours of symptom onset. METHODS: We studied consecutive
      patients treated with iv rt-PA for acute stroke, with prospective follow up of up
      to 3 years. Outcome measures included National Institutes of Health Stroke Scale
      (NIHSS) score, Barthel Index (BI), modified Rankin score (MRS), and stroke
      mortality. Patients were split into two groups: younger (< or =79 years) and
      older (> or =80 years). RESULTS: There were 65 patients in the younger cohort and
      31 patients in the older. Older patients were more likely to present with more
      severe baseline stroke (p = 0.04; odds ratio (OR) 3.04; 95% confidence interval
      (CI) 1.03 to 8.98). Stroke mortality at 90 days was 10.8% in the younger and
      32.3% in the older cohort (p = 0.01). At 90 days' follow up, patients in the
      older cohort with more severe stroke (NIHSS score > or =11) were nearly 10 times
      more likely to have poor outcome compared with their younger counterparts
      presenting with severe stroke (p = 0.001; OR = 10.36; 95% CI 2.16 to 49.20).
      Baseline stroke severity and age were the only independent and equal predictors
      for stroke outcome. No threshold was found for age or baseline stroke severity
      predicting outcome. CONCLUSION: Older patients presenting with more severe
      baseline stroke are much less likely to benefit from iv rt-PA as compared with
      their younger counterparts.

PMID- 16107358
TI  - Outcome in patients with basilar artery occlusion treated conventionally.
AB  - BACKGROUND: Most data on the outcome of basilar artery occlusion are from recent
      case series of patients treated with intra-arterial thrombolysis. The limited
      knowledge on the outcome after a conventional treatment approach comes from a few
      small case series of highly selected patients. OBJECTIVE: To provide more data on
      the outcome of conventional treatment. METHODS: Data were analysed on patients
      from three centres with symptomatic basilar artery occlusion treated
      conventionally. Conventional therapy was defined as treatment with antiplatelets,
      anticoagulation, or both. RESULTS: Data were available on 82 patients. The case
      fatality was 40%. Among survivors, 65% remained dependent (Rankin score 4-5).
      Patients younger than 60 years (odds ratio = 3.1 (95% confidence interval, 1.0 to
      9.5)) and those with a minor stroke (OR = 3.1 (1.0 to 9.6)) were more likely to
      have a good outcome (Rankin score 0-3). Patients with a progressive stroke were
      less likely to have a good outcome (OR = 0.3 (0.08 to 1.2)) than patients with a
      maximum deficit at onset or fluctuating symptoms at presentation. CONCLUSIONS:
      Conventional treatment of symptomatic basilar artery occlusion is associated with
      a poor outcome in almost 80% of patients, which emphasises the importance of the
      search for a more effective treatment approach.

PMID- 16107359
TI  - Marshall Hall and "Romberg's sign".

PMID- 16107360
TI  - Functional analysis of a recurrent missense mutation in Notch3 in CADASIL.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is an inherited vascular dementia characterised
      by recurrent ischemic strokes in the deep white matter. Mutations in the gene
      encoding the cell surface receptor, Notch3, have been identified in CADASIL
      patients, and accumulation of the extracellular domain of Notch3 has been
      demonstrated in affected vessels. Almost all CADASIL mutations alter the number
      of cysteine residues in the epidermal growth factor (EGF)-like repeats in the
      extracellular domain of the protein. OBJECTIVES: To understand the functional
      consequences of a recurrent CADASIL mutation on furin processing, cell surface
      expression, ligand binding, and activation of a downstream effector CBF1 by the
      Notch3 receptor. METHODS: We expressed wild type and mutant Notch3 receptors in
      cultured cells and examined cell surface expression of the proteins. We also
      applied a new flow cytometry based approach to semi-quantitatively measure
      binding to three Notch ligands. Additionally, we used a well characterised co
      culture system to examine ligand dependent activation of transcription from a
      CBF1-luciferase reporter construct. RESULTS: These studies revealed subtle
      abnormalities in furin processing of the mutant receptor, although both
      heterodimeric and full length receptors are present on the cell surface, are
      capable of interacting with soluble forms of three ligands, Delta1, Delta4, and
      Jagged1, and retain the ability to activate CBF1 in a ligand dependent manner.
      CONCLUSIONS: By comparison with other mutant forms of Notch3, these data indicate
      that individual CADASIL mutations can have disparate effects on Notch3 expression
      and function.

PMID- 16107361
TI  - Increased platelet count and leucocyte-platelet complex formation in acute
      symptomatic compared with asymptomatic severe carotid stenosis.
AB  - OBJECTIVE: The risk of stroke in patients with recently symptomatic carotid
      stenosis is considerably higher than in patients with asymptomatic stenosis. In
      the present study it was hypothesised that excessive platelet activation might
      partly contribute to this difference. METHODS: A full blood count was done and
      whole blood flow cytometry used to measure platelet surface expression of CD62P,
      CD63, and PAC1 binding and the percentage of leucocyte-platelet complexes in
      patients with acute (0-21 days, n = 19) and convalescent (79-365 days)
      symptomatic (n = 16) and asymptomatic (n = 16) severe (> or =70%) carotid
      stenosis. Most patients were treated with aspirin (37.5-300 mg daily) although
      alternative antithrombotic regimens were more commonly used in the symptomatic
      group. RESULTS: The mean platelet count was higher in patients with acute and
      convalescent symptomatic compared with asymptomatic carotid stenosis. There were
      no significant differences in the median percentage expression of CD62P and CD63,
      or PAC1 binding between the acute or convalescent symptomatic and asymptomatic
      patients. The median percentages of neutrophil-platelet (p = 0.004), monocyte
      platelet (p = 0.046), and lymphocyte-platelet complexes (p = 0.02) were higher in
      acute symptomatic than in asymptomatic patients. In patients on aspirin
      monotherapy, the percentages of neutrophil-platelet and monocyte-platelet
      complexes (p = 0.03) were higher in acute symptomatic (n = 11) than asymptomatic
      patients (n = 14). In the convalescent phase, the median percentages of all
      leucocyte-platelet complexes in the symptomatic group dropped to levels similar
      to those found in the asymptomatic group. CONCLUSION: Increased platelet count
      and leucocyte-platelet complex formation may contribute to the early excess risk
      of stroke in patients with recently symptomatic carotid stenosis.

PMID- 16107362
TI  - Is inflammation important in early PPMS? a longitudinal MRI study.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) studies in primary progressive
      multiple sclerosis (PPMS) have shown a reduced frequency of enhancement with the
      contrast agent gadolinium-DTPA (Gd-DTPA), in comparison with relapsing-remitting
      multiple sclerosis (RRMS), and it has been suggested that there may be a less
      important role for inflammation in its pathogenesis. However, the earliest
      clinical stages of PPMS have not been studied and thus it has not been possible
      to exclude the existence of an early inflammatory phase. OBJECTIVE: To study the
      presence, characteristics, and implications of inflammation in early PPMS.
      METHODS: 45 patients with a mean disease duration of 3.3 years had triple dose Gd
      enhanced MRI, expanded disability status scale (EDSS), and multiple sclerosis
      functional composite (MSFC) assessments at baseline. Repeat MRI was done at 1 and
      2 months in 24 patients, and at 6 months in 38. RESULTS: Enhancing brain lesions
      were present in 42% of patients at baseline but enhancing cord lesions were
      uncommon (7%); 85% of enhancing lesions enhanced for one month or less. Patients
      with enhancing lesions had greater disability (EDSS, p = 0.027; MSFC, p = 0.026)
      and more MRI abnormalities (greater T2 load, p = 0.008; greater T1 hypointensity
      load, p = 0.001; and reduced partial brain volume, p = 0.012) than those without
      enhancement. Enhancement at 6 months was seen in 32% of patients and was
      restricted to a subset of patients who enhanced at baseline. CONCLUSIONS:
      Enhancement is present in some cases of early PPMS and is associated with greater
      disease impact in terms of both clinical and MRI measures.

PMID- 16107363
TI  - Motor neurone excitability in back muscles assessed using mechanically evoked
      reflexes in spinal cord injured patients.
AB  - OBJECTIVE: The clinical and functional assessment of back muscles in human spinal
      cord injury (SCI) has received little attention. The aim of this study was to
      develop a method to assess the level of a thoracic spinal cord lesion based on
      the reflex activation of back muscles. METHODS: In 11 control subjects and in 12
      subjects with clinically complete thoracic SCI (T2-T12), either a spinous process
      or an erector spinae muscle was prodded to elicit short latency reflexes recorded
      electromyographically at the spinal level of stimulation. An electromagnetic
      servo, attached to a blunt probe, applied stimuli at a frequency of 1 Hz and
      amplitude of 3 mm. Two trials of 50 mechanical prods were conducted at each site.
      RESULTS: Reflexes were evoked in control subjects in 82% of trials when the
      spinous process was prodded, and in 80% of trials when the muscle was prodded. In
      contrast, reflexes in SCI subjects could be elicited in 90-100% of trials two
      segments either above or below the lesion. Reflex responses in control subjects
      had a mean (SEM) latency of 5.72 (0.53) ms when the spinous process was prodded,
      and 5.42 (0.42) ms when the muscle was prodded. In the SCI subjects, responses
      had slightly (but insignificantly) longer latencies both above and below the
      lesion to either stimulus. The amplitude of reflex responses, expressed as a
      percentage of the background EMG, was on average 2-3 times larger at the three
      vertebral levels spanning the lesion in SCI subjects than at sites above or below
      the lesion or at any level in control subjects. CONCLUSION: We propose that the
      size of these mechanically evoked reflexes may be useful in determining the level
      of thoracic SCI. Furthermore, the reflexes might provide a valuable tool with
      which to monitor recovery after an intervention to repair or improve function of
      a damaged spinal cord.

PMID- 16107364
TI  - A practical definition of conduction block in IvIg responsive multifocal motor
      neuropathy.
AB  - BACKGROUND: Multifocal motor neuropathy with conduction block (MMN) can be
      mistaken for motor neurone disease or other lower motor neurone syndromes, but is
      treatable with intravenous immunoglobulin (IvIg). Formal electrophysiological
      criteria for conduction block (CB) are so stringent that substantial numbers of
      patients may miss out on appropriate treatment. METHODS: Electrophysiological
      data were collected from 10 healthy volunteers and compared to data from 10
      patients who satisfied the clinical criteria for MMN and who responded to IvIg.
      This produced a definition of CB in MMN patients which was compared with existing
      definitions to assess "miss rates". RESULTS: Mean values for compound muscle
      action potential area, amplitude, and duration were calculated in normal
      subjects. Results beyond 3 SD of their respective means were considered abnormal.
      Using these criteria, CB in the context of MMN was defined as a reduction in
      negative peak area >23% along a distal nerve segment or >29% across a proximal
      segment; or a reduction in amplitude >32% across a distal segment or >33% across
      a proximal segment. All IvIg responsive patients had at least one nerve segment
      showing such CB. Employing some criteria from the literature would have denied
      treatment to over 30% of responsive patients. CONCLUSION: In the clinical setting
      of suspected MMN, less stringent criteria for CB can improve the diagnosis of
      this treatable disorder. Exclusions on grounds of temporal dispersion may be over
      restrictive. A little over one third of CBs occur proximally.

PMID- 16107365
TI  - Delayed recovery of ulnar neuropathy due to elbow warming.

PMID- 16107366
TI  - The effect of treatment upon temporal dispersion in IvIg responsive multifocal
      motor neuropathy.
AB  - BACKGROUND: Multifocal motor neuropathy with conduction block (MMN) is a
      treatable disorder that can be mistaken for other lower motor neurone syndromes.
      Existing electrophysiological diagnostic criteria for MMN are restrictive. In
      particular, many are cautious about diagnosing conduction block (CB) in the
      presence of abnormal temporal dispersion (TD). OBJECTIVE: To study the
      significance of TD in MMN, its relationship to CB in intravenous immunoglobulin
      (IvIg) responsive patients, and its utility in detecting a treatment response.
      METHODS: We compared pre- and post-treatment changes in CB and TD in nine
      patients who satisfied clinical and electrophysiological criteria for MMN and
      responded to IvIg. RESULTS: TD improved in one or more nerve segments in eight of
      nine patients tested. There was marked improvement in 65% of all nerve segments,
      and 60% of those segments with CB. By comparison, significant improvement in CB
      occurred in only 33% of segments. Of segments with significantly better CB after
      treatment, all but one showed similar improvements in TD. Such changes were not
      related to the degree of TD before treatment, being seen in segments with
      abnormal as well as normal TD. There was no correlation between improvements seen
      in TD and CB. CONCLUSION: We believe that TD should be considered an inherent
      feature of MMN. Improvement in TD is an independent marker of
      electrophysiological improvement in this disorder and is likely to be more useful
      than CB. When MMN is clinically suspected, the use of stringent criteria for CB
      in the presence of TD should be avoided.

PMID- 16107367
TI  - The Depression Intensity Scale Circles (DISCs): a first evaluation of a simple
      assessment tool for depression in the context of brain injury.
AB  - OBJECTIVE: To assess the validity, responsiveness, and test-retest reliability of
      DISCs (Depression Intensity Scale Circles) as a simple screening tool for
      depression in patients with cognitive or communicative deficits following
      acquired brain injury. DESIGN: Cohort analysis of consecutive patients entered
      into an integrated care pathway for screening and management of depression in the
      context of rehabilitation. SETTING: Regional neurological rehabilitation service
      in the UK. PARTICIPANTS: 114 patients with complex disabilities caused by
      acquired brain injury (mean (SD) age, 42.8 (14.5) years). MAIN OUTCOME MEASURES:
      DISCs (a graphic rating scale depicting six circles with increasing proportion of
      dark shading), Numbered Graphic Rating Scale (NGRS), Yale single question ("Do
      you often feel sad or depressed"), Beck Depression Inventory-II (BDI-II), DSM-IV
      criteria for depression. RESULTS: At initial assessment the DISCs correlated with
      total BDI-II scores (Spearman rho = 0.66, p < 0.001), NGRS (rho = 0.87, p<0.001),
      and DSM-IV (rho = 0.59, p<0.001). A DISCs score > or =2 identified depression
      (major or minor) according to DSM-IV criteria with 60% sensitivity, 87%
      specificity, 75% positive predictive value, and 77% negative predictive value.
      Test-retest reliability after 24 hours (n = 66) showed "excellent" level of
      agreement (weighted kappa = 0.84). In 45 patients who received intervention for
      depression, the DISCs showed a significant change in response to treatment
      (Wilcoxon; p<0.001). CONCLUSIONS: DISCs had acceptable convergent validity,
      reliability, and responsiveness as a simple graded tool for screening and
      assessment of depression in patients with complex disabilities following acquired
      brain injury. It warrants further investigation in patients with more profound
      language and cognitive deficits for which it is primarily intended.

PMID- 16107368
TI  - Abnormal cortical excitability in sporadic but not homozygous D90A SOD1 ALS.
AB  - BACKGROUND: Excitotoxicity is one pathogenic mechanism proposed in amyotrophic
      lateral sclerosis (ALS), and loss of cortical inhibitory influence may be
      contributory. Patients with ALS who are homozygous for the D90A superoxide
      dismutase-1 (SOD1) gene mutation (homD90A) have a unique phenotype, associated
      with prolonged survival compared with patients with sporadic ALS (sALS). In this
      study, transcranial magnetic stimulation (TMS) was used to explore cortical
      excitation and inhibition. Flumazenil binds to the benzodiazepine subunit of the
      GABA(A) receptor, and (11)C-flumazenil positron emission tomography (PET) was
      used as a marker of cortical neuronal loss and/or dysfunction, which might in
      turn reflect changes in cortical inhibitory GABAergic mechanisms. METHODS:
      Cortical responses to single and paired stimulus TMS were compared in 28 patients
      with sALS and 11 homD90A patients versus 24 controls. TMS measures included
      resting motor threshold, central motor conduction time, silent period,
      intracortical inhibition (ICI), and facilitation. (11)C-flumazenil PET of the
      brain was performed on 20 patients with sALS and nine with homD90A. Statistical
      parametric mapping was used to directly compare PET images from the two patient
      groups to identify those areas of relatively reduced cortical (11)C-flumazenil
      binding that might explain differences in cortical excitability seen using TMS.
      RESULTS: Increased cortical excitability, demonstrated by reduction in ICI, was
      seen in the patients with sALS but not the homD90A patients. A relative reduction
      in cortical (11)C-flumazenil binding was found in the motor and motor association
      regions of the superior parietal cortices of the patients with sALS. CONCLUSIONS:
      A cortical inhibitory deficit in sALS was not demonstrable in a homogeneous
      genetic ALS population of similar disability, suggesting a distinct cortical
      vulnerability. (11)C-flumazenil PET demonstrated that neuronal loss/dysfunction
      in motor and motor association areas may underlie this difference. The corollary,
      that there may be relative preservation of neuronal function in these areas in
      the homD90A group, has implications for understanding the slower progression of
      disease in these patients.

PMID- 16107369
TI  - Progression of cerebral white matter lesions in Alzheimer's disease: a new window
      for therapy?
AB  - BACKGROUND: White matter lesions (WML) are a risk factor for Alzheimer's disease.
      Progression of WML is associated with vascular factors and cognitive decline in
      population based studies but the course of WML is unknown in Alzheimer's disease.
      OBJECTIVE: To investigate the prevalence and risk factors for progression of WML
      in Alzheimer's disease. SUBJECTS: 38 patients with Alzheimer's disease for whom
      blood pressure measurements and sequential brain MRIs were available. METHODS:
      The proportion of patients with progression of WML was calculated, stratified on
      baseline absence or presence of WML by analysis of variance. Odds ratios (OR)
      were calculated by age and sex adjusted logistic regression to quantify the
      relation between blood pressure and progression of WML. RESULTS: About 25% of the
      patients showed progression of WML. Patients with WML at baseline had
      significantly more progression than those without WML at baseline (adjusted mean
      difference = 1.2; 95% confidence interval (CI), 0.6 to 1.8). Diastolic blood
      pressure (DBP) was particularly related to progression of WML (OR = 5.9 (95% CI,
      1.0 to 37.6) per 10 mm Hg DBP, p = 0.05). CONCLUSIONS: Alzheimer's disease
      patients with WML at baseline are at risk for rapid progression of WML. WML may
      offer a potential treatment target in this disease to ameliorate the rate of
      cognitive decline.

PMID- 16107370
TI  - Decline in intelligence is associated with progression in white matter
      hyperintensity volume.
AB  - OBJECTIVES: To quantify the time course of white matter hyperintensities (WMH)
      and assess the association between progression and cognitive decline in non
      demented octogenarians. METHODS: From a Danish cohort of 698 people born in 1914,
      26 participated in neuropsychological assessment (Wechsler adult intelligence
      scale) initiated at age 50, including cognitive testing and cerebral magnetic
      resonance imaging at the 80 and 85 year studies. WMH volumes were quantified and
      partial correlations were calculated between WMH volume change and decline in
      WAIS scores from 80 to 85. RESULTS: Progression in WMH volume ranged from 0 ml to
      20.7 ml, providing a median increase of 2.6 ml (range 0.1 to 20.7, p<0.001) and,
      with a mean time interval between scans of 3.8 years, a rate of progression of
      0.63 (0 to 6.8) ml/year. WMH volume measures for the two hemispheres were highly
      correlated (r = 0.95) and did not differ significantly. Increase in WMH volume
      was correlated with a simultaneous decline in verbal IQ (r = -0.65, p = 0.001),
      while baseline WMH was associated with subsequent decline in performance subtests
      (digit symbol, r = -0.57, p = 0.02). CONCLUSIONS: The association between WMH and
      decline in essential cognitive abilities even in well preserved elderly people
      suggests that WMH should be regarded as a risk factor for cognitive impairment
      and dementia.

PMID- 16107371
TI  - Contralateral pharyngeal paralysis caused by medial medullary infarction.
AB  - A patient with unilateral upper medial medullary infarction presented with
      contralateral paralysis of the pharyngeal constrictor muscle in association with
      lemniscal sensory loss, pyramidal insufficiency, and central facial palsy on the
      same side. Individual differences in supranuclear control of the pharyngeal
      muscles may explain this rare occurrence. The combination of these signs is
      described as a syndrome of upper medial medullary lesion.

PMID- 16107372
TI  - A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing
      remitting multiple sclerosis.
AB  - BACKGROUND: Epidemiological and ecological studies suggest links between vitamin
      D deficiency and increased multiple sclerosis (MS) prevalence. OBJECTIVE: To
      evaluate the safety and tolerability of oral calcitriol therapy in an open label
      pilot study. METHODS: 15 ambulatory patients with relapsing-remitting MS and at
      least one clinical relapse within the previous 12 months received oral calcitriol
      (target dose: 2.5 microg/d) for 48 weeks. Dietary calcium was restricted to 800
      mg/d. Patients were monitored using frequent clinical and laboratory
      examinations, the expanded disability status scale (EDSS), and brain magnetic
      resonance imaging (MRI). RESULTS: Two patients withdrew because of symptomatic
      hypercalcaemia (serum calcium >3.35 mmol/l in each case) resulting from
      persistent dietary indiscretion. Two diet compliant patients required temporary
      dose adjustments for mild asymptomatic hypercalcaemia. Diet compliant patients
      experienced mild adverse effects. The on-study exacerbation rate (27%) was less
      than baseline. Four patients experienced five clinical relapses but only one
      patient worsened by >1 EDSS point. Brain MRI revealed enhancing lesions in five
      patients at baseline (33%) and in four (29%) at both 24 and 48 weeks.
      CONCLUSIONS: Oral calcitriol is safe and well tolerated for up to one year by
      diet compliant relapsing-remitting MS patients. Further study of vitamin D
      related mechanisms is warranted in MS.

PMID- 16107373
TI  - Dysphagia as the sole manifestation of myasthenia gravis.
AB  - Three patients are described who had dysphagia as the sole manifestation of
      myasthenia gravis. Severity ranged from the need to be fed by nasogastric tube to
      moderate dysphagia requiring only diet change. Oesophageal manometry was carried
      out in two patients and showed generalised weakness of peristaltic contractions
      which included the smooth muscle part of the oesophagus. These disturbances
      worsened with repeated swallows. They were partly reversed by intravenous
      edrophonium and by rest. Repetitive nerve stimulation was normal in all three
      patients, but stimulated single fibre EMG of the frontalis muscle showed that all
      had impairment of neuromuscular transmission. Anti-AChR antibodies were found in
      only one patient. The most affected patient was treated with pyridostigmine,
      plasmapheresis, and high dose prednisone. The remaining two patients received
      only oral anticholinesterases.

PMID- 16107374
TI  - Syncope associated with pain as the presenting feature of neck malignancy:
      failure of cardiac pacemaker to prevent attacks in two cases.
AB  - Two patients are described in whom syncope was the presenting clinical feature of
      an undiagnosed neck malignancy. Both patients also had attacks associated with
      paroxysms of severe neck pain. Neither patient responded to cardiac pacing.

PMID- 16107375
TI  - Remission of progressive multifocal leucoencephalopathy in SLE after treatment
      with cidofovir: a 4 year follow up.

PMID- 16107376
TI  - Dramatic improvement in non-AIDS related progressive multifocal
      leucoencephalopathy.

PMID- 16107377
TI  - Diaphragmatic paralysis and respiratory failure as a complication of Lyme
      disease.

PMID- 16107378
TI  - Benign paroxysmal positional vertigo (BPPV) predominantly affects the right
      labyrinth.

PMID- 16107379
TI  - Aciclovir induced posterior leucoencephalopathy.

PMID- 16107380
TI  - Normal memory and no confabulation after extensive damage to the orbitofrontal
      cortex.

PMID- 16107381
TI  - Adult onset SSPE: experiences in West Yorkshire over a 12 month period.

PMID- 16107382
TI  - Laterality of symptoms in patients admitted to a stroke unit who had a discharge
      diagnosis of a psychiatric condition.

PMID- 16107384
TI  - Neuroradiology.

PMID- 16107385
TI  - Imaging in multiple sclerosis.

PMID- 16107386
TI  - Imaging of acute stroke and transient ischaemic attack.

PMID- 16107387
TI  - Imaging in epilepsy.

PMID- 16107388
TI  - Syndromes of the orbital fissure, cavernous sinus, cerebello- pontine angle, and
      skull base.

PMID- 16107389
TI  - The neurologist in the DGH: how to survive without on site neuroradiolgy.

PMID- 16107390
TI  - Interventional neuroradiology.

PMID- 16107391
TI  - Effect of vacuum-condensed or ultrafiltered milk on pasteurized process cheese.
AB  - Milk was concentrated by ultrafiltration (UF) or vacuum condensing (CM) and milks
      with 2 levels of protein: 4.5% (UF1 and CM1) and 6.0% (UF2 and CM2) for
      concentrates and a control with 3.2% protein were used for manufacturing 6
      replicates of Cheddar cheese. For manufacturing pasteurized process cheese, a 1:1
      blend of shredded 18- and 30-wk Cheddar cheese, butter oil, and disodium
      phosphate (3%) was heated and pasteurized at 74 degrees C for 2 min with direct
      steam injection. The moisture content of the resulting process cheeses was 39.4
      (control), 39.3 (UF1), 39.4 (UF2), 39.4 (CM1), and 40.2% (CM2). Fat and protein
      contents were influenced by level and method of concentration of cheese milk. Fat
      content was the highest in control (35.0%) and the lowest in UF2 (31.6%), whereas
      protein content was the lowest in control (19.6%) and the highest in UF2
      (22.46%). Ash content increased with increase in level of concentration of cheese
      milk with no effect of method of concentration. Meltability of process cheeses
      decreased with increase in level of concentration and was higher in control than
      in the cheeses made with concentrated milk. Hardness was highest in UF cheeses
      (8.45 and 9.90 kg for UF1 and UF2) followed by CM cheeses (6.27 and 9.13 kg, for
      CM1 and CM2) and controls (3.94 kg). Apparent viscosity of molten cheese at 80
      degrees C was higher in the 6.0% protein treatments (1043 and 1208 cp, UF2 and
      CM2) than in 4.5% protein treatments (855 and 867 cp, UF1 and CM1) and in control
      (557 cp). Free oil in process cheeses was influenced by both level and method of
      concentration with control (14.3%) being the lowest and CM2 (18.9%) the highest.
      Overall flavor, body and texture, and acceptability were higher for process
      cheeses made with the concentrates compared with control. This study demonstrated
      that the application of concentrated milks (UF or CM) for Cheddar cheese making
      has an impact on pasteurized process cheese characteristics.

PMID- 16107392
TI  - Shelf life of Crescenza cheese as measured by electronic nose.
AB  - The shelf life of Crescenza, a traditional Italian soft cheese, was measured
      using classical analysis and a commercial electronic nose. Two lots of samples
      directly supplied by a manufacturer at the beginning of their commercial life
      were stored at 2 constant temperatures (8 and 15 degrees C) and analyzed until
      their respective expiration dates. Among the physicochemical parameters, pH,
      acidity, hue, and apparent yield rheological index appeared to be the best
      predictors of the quality decay. Changes in these indices were described with a
      sigmoidal transition function allowing definition of a loose and a severe shelf
      life protocol, based on the trend of first and second time derivatives. A time
      range of 1 to 3 d at 15 degrees C and 4 to 8 d at 8 degrees C was accordingly
      assessed to maintain the freshness of Crescenza cheese. The quality decay of
      cheese aroma was evaluated by inspecting the headspace fingerprint of the same
      set of samples using the electronic nose. Sample classification through the aroma
      fingerprint confirmed the predicted shelf-life time ranges. A clear
      discrimination between "fresh," "aged," and "very aged" samples was obtained
      using principal components analysis, cluster analysis, and linear discriminant
      analysis statistical techniques. The predictive ability of the linear
      discriminant analysis classification model was confirmed by considering a new set
      of cheese samples purchased at the beginning of their commercial life from a
      local market and analyzed until their expiration date.

PMID- 16107393
TI  - Rheology, microstructure, and functionality of low-fat Iranian white cheese made
      with different concentrations of rennet.
AB  - A batch of full-fat (23% target fat) and 3 batches of low-fat (6% target fat)
      Iranian white cheese with different rennet concentrations (1-, 2-, and 3-fold the
      normal usage) were produced to study the effect of fat content reduction and
      promoted proteolysis on the textural and functional properties of the product.
      Cheese samples were analyzed with respect to their rheological parameters
      (uniaxial compression and small amplitude oscillatory shear), meltability,
      microstructure, and sensory characteristics. Reduction of fat content from 23 to
      6% had adverse effects on the texture, functionality, cheese-making yield, and
      sensory characteristics of Iranian white cheese. Fat reduction increased the
      instrumental hardness parameters (storage modulus, stress at fracture, and
      Young's modulus of elasticity), decreased the cheese meltability and yield, and
      made the microstructure more compact. Doubling the rennet concentration reduced
      values of instrumental hardness parameters, increased the meltability, and
      improved the sensory impression of texture. Although increasing the rennet
      concentration to 2-fold the normal usage resembled somewhat the low-fat cheese to
      its full-fat counterpart, it appeared to cause more reduction in yield.
      Increasing the rennet concentration 3-fold the normal usage produced a product
      slightly more elastic than the low-fat cheese with normal concentration of
      rennet. Increasing the rennet concentration to 2-fold the normal usage was useful
      for improving the textural, functional, and sensory properties of low-fat Iranian
      white cheese.

PMID- 16107394
TI  - Transfer of aflatoxin B1 from feed to milk and from milk to curd and whey in
      dairy sheep fed artificially contaminated concentrates.
AB  - An experiment was carried out using dairy ewes to study the transfer of aflatoxin
      B1 (AFB1) from feed to milk and from milk to cheese. The effects of AFB1 on liver
      function and hematological parameters were also investigated. Fifteen ewes were
      assigned to treatments in replicated 3 x 3 Latin squares. The experimental groups
      received 32, 64, or 128 microg/d of pure AFB1 for 7 d followed by 5 d of
      clearance. On the sixth day of the first period, the total daily milk produced by
      each ewe was collected separately and processed into cheese. The results indicate
      that the level of AFB1 used did not adversely affect animal health and milk
      production traits. The aflatoxin M1 (AFM1) concentrations in milk approached a
      steady-state condition in all treated groups between 2 and 7 d after the start of
      treatment. The mean AFM1 concentrations of treated groups in steady-state
      condition (184.4, 324.7, and 596.9 ng/kg in ewes fed 32, 64, or 128 microg of
      AFB1, respectively) were significantly affected by the AFB1 doses. The AFM1
      concentration was linearly related to the AFB1 intake/kg of BW. The carry-over
      values of AFB1 from feed into AFM1 in milk (0.26 to 0.33%) were not influenced by
      the AFB1 doses. The AFM1 concentrations in curd and whey were linearly related to
      the AFM1 concentrations in the unprocessed milk.

PMID- 16107395
TI  - Effects of emulsifying salts on the turbidity and calcium-phosphate-protein
      interactions in casein micelles.
AB  - Influence of emulsifying salts (ES) on some physical properties of casein
      micelles was investigated. A reconstituted milk protein concentrate (MPC)
      solution (5% wt/wt) was used as the protein source and the effects of ES [0 to
      2.0% (wt/wt)] were estimated by measuring turbidity, acid-base titration curves
      and amount of casein-bound Ca and inorganic P (P(i)). Various ES, trisodium
      citrate (TSC), or sodium phosphates (ortho-, pyro-, or hexameta-) were added to
      MPC solution, and all samples were adjusted to pH 5.8. Acid-base buffering curves
      were used to observe changes in the amount and type of insoluble Ca phosphates.
      An increase in the concentration of TSC added to MPC solution decreased
      turbidity, buffering at pH approximately 5 (contributed by colloidal Ca
      phosphate), and amount of casein-bound Ca and P(i). Addition of up to 0.7%
      disodium orthophosphate (DSP) did not significantly influence turbidity,
      buffering curves, or amount of casein-bound Ca and P(i). When higher
      concentrations (i.e., > or =1.0%) of DSP were added, there was a slow decrease in
      turbidity. With increasing concentration of added tetrasodium pyrophosphate
      (TSPP), turbidity and buffering at pH approximately 5 decreased, and amount of
      casein-bound Ca and P(i) increased. When small concentrations (i.e., 0.1%) of
      sodium hexameta-phosphate were added, effects were similar to those when TSPP
      were added but when higher concentrations (i.e., > or =0.5%) were added, the
      buffering peak shifted to a higher pH value, and amount of casein-bound Ca and
      P(i) decreased. These results suggested that each type of ES influenced casein
      micelles by different mechanisms.

PMID- 16107396
TI  - Short communication: Pasteurization of milk abolishes bovine herpesvirus 4
      infectivity.
AB  - Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus highly prevalent in the
      cattle population that has been isolated from the milk and the serum of healthy
      infected cows. Several studies reported the sensitivity and the permissiveness of
      some human cells to BoHV-4 infection. Moreover, our recent study demonstrated
      that some human cells sensitive but not permissive to BoHV-4 support a persistent
      infection protecting them from tumor necrosis factor-alpha-induced apoptosis.
      Together, these observations suggested that BoHV-4 could represent a danger for
      public health. To evaluate the risk of human infection by BoHV-4 through milk or
      serum derivatives, we investigated the resistance of BoHV-4 to the mildest
      thermal treatments usually applied to these products. The results demonstrated
      that milk pasteurization and thermal decomplementation of serum abolish BoHV-4
      infectivity by inactivation of its property to enter permissive cells.
      Consequently, our results demonstrate that these treatments drastically reduce
      the risk of human infection by BoHV-4 through treated milk or serum derivatives.

PMID- 16107397
TI  - Altering the fatty acids in milk fat by including canola seed in dairy cattle
      diets.
AB  - The objective was to evaluate the effects of feeding ground canola seed on the
      fatty acid profile, yield, and composition of milk from dairy cows. Twenty-four
      multiparous Holstein cows (548.3 +/- 11.9 kg body weight and 28 +/- 9 d in
      lactation) were randomly assigned to 1 of 2 treatments: Control (CON) or ground
      canola seed treatment (GCS) with 14% [of diet dry matter (DM)] of the total
      ration as ground canola seed containing 34% lipid. Diets contained 20% crude
      protein, but varied in net energy as a result of fat content differences of 2.5%
      and 6.4% (DM) for CON and GCS, respectively. Diets were composed of corn, corn
      silage, alfalfa (50:50 ground hay and haylage, DM basis), soybean and blood meal,
      and vitamins and minerals. Mechanically extruded canola meal was used in the CON
      diet to adjust for the protein from canola seed in the GCS diet. Cows were housed
      in tie-stalls and fed and milked twice daily for 10 wk. The inclusion of ground
      canola seed did not alter DM intake, weight gain, or body condition score of
      cows. Milk fat from GCS cows had greater proportions of long-chain fatty acids (>
      or = 18 carbons) and a lower ratio of n-6 to n-3 fatty acids. Feeding GCS reduced
      the proportion of short- and medium-chain fatty acids. Milk fat from cows fed GCS
      had a greater proportion of vaccenic acid and tended to have a higher proportion
      of cis-9,trans-11 conjugated linoleic acid. Actual and 3.5% fat-corrected milk
      yields were similar between treatments. The milk fat and protein percentages were
      lower for GCS cows, but total yield of these components was similar between
      treatments. Milk urea nitrogen was lower and serum urea nitrogen tended to be
      lower in cows fed canola seed. Serum glucose, insulin, and nonesterified fatty
      acids were not altered, but serum triglycerides were higher in GCS cows. Ammonia
      and total volatile fatty acids tended to be lower in ruminal fluid from GCS cows;
      rumen pH was unchanged. Feeding canola seed to lactating dairy cows resulted in
      milk fat with higher proportions of healthful fatty acids without affecting milk
      yield or composition of milk.

PMID- 16107398
TI  - Influence of storage and preservation on fossomatic cell count and composition of
      goat milk.
AB  - This study was designed to evaluate the effects of different test conditions on
      the somatic cell count (SCC) and composition of goat milk. To this end, 3600
      tests were performed on 1800 aliquots taken from 40 goat milk samples using a
      combined instrument set-up based on flow cytometry for SCC and Fourier transform
      infrared analysis for fat, total protein, lactose, total solids, and freezing
      point determinations. The conditions tested were storage temperature
      (refrigeration and freezing), use of a preservative [no preservative (NP),
      azidiol (AZ), and bronopol (BR)], and age of the milk samples at each storage
      temperature (24 h to 42 d at refrigeration temperature and 21 to 105 d at
      freezing temperature). Significant effects on logSCC variation were shown by the
      storage temperature, the preservation treatment, the interaction of storage
      temperature x preservation treatment, and milk age within the interaction of
      storage temperature x preservative. Highest counts were recorded in the BR
      preserved milk samples (logSCC = 5.877), and lowest counts were recorded in milk
      samples preserved using AZ (logSCC = 5.803). The use of frozen/thawed samples led
      to a significantly decreased logSCC for the treatments AZ and NP; the logSCC was
      not modified when BR-preserved frozen/thawed samples were analyzed. During
      storage, variations in the SCC observed for BR-preserved samples stored at
      refrigeration temperature for up to 25 d and at freezing temperature for all
      times tested were always < 10%. The preservation treatment was the main factor
      affecting the milk composition variables examined. Highest values of most
      variables were obtained in the BR-preserved samples, and the lowest values were
      obtained in the AZ-preserved samples. The freezing point was lower in the
      preserved samples than in the NP samples. The levels of milk constituents
      recorded in the BR-preserved samples were independent of both the storage
      temperature and age of milk sample. Our findings indicate that the freezing point
      of goat milk must be interpreted according to the preservative used.

PMID- 16107399
TI  - Chymosin-mediated proteolysis, calcium solubilization, and texture development
      during the ripening of cheddar cheese.
AB  - Full fat, milled-curd Cheddar cheeses (2 kg) were manufactured with 0.0
      (control), 0.1, 1.0, or 10.0 micromol of pepstatin (a potent competitive
      inhibitor of chymosin) added per liter of curds/whey mixture at the start of
      cooking to obtain residual chymosin levels that were 100, 89, 55, and 16% of the
      activity in the control cheese, respectively. The cheeses were ripened at 8
      degrees C for 180 d. There were no significant differences in the pH values of
      the cheeses; however, the moisture content of the cheeses decreased with
      increasing level of pepstatin addition. The levels of pH 4.6-soluble nitrogen in
      the 3 cheeses with added pepstatin were significantly lower than that of the
      control cheese at 1 d and throughout ripening. Densitometric analysis of urea
      PAGE electro-phoretograms of the pH 4.6-insoluble fractions of the cheese made
      with 10.0 micromol/L of pepstatin showed complete inhibition of hydrolysis of
      alpha(S1)-casein (CN) at Phe23-Phe24 at all stages of ripening. The level of
      insoluble calcium in each of 4 cheeses decreased significantly during the first
      21 d of ripening, irrespective of the level of pepstatin addition. Concurrently,
      there was a significant reduction in hardness in each of the 4 cheeses during the
      first 21 d of ripening. The softening of texture was more highly correlated with
      the level of insoluble calcium than with the level of intact alpha(S1)-CN in each
      of the 4 cheeses early in ripening. It is concluded that hydrolysis of alpha(S1)
      CN at Phe23-Phe24 is not a prerequisite for softening of Cheddar cheese during
      the early stages of ripening. We propose that this softening of texture is
      principally due to the partial solubilization of colloidal calcium phosphate
      associated with the para-CN matrix of the curd.

PMID- 16107400
TI  - Application of polymerase chain reaction to detect adulteration of sheep's milk
      with goats' milk.
AB  - The polymerase chain reaction has been applied for the specific detection of
      goats' milk in sheep's milk using primers targeting the mitochondrial 12S
      ribosomal RNA gene. The use of goat-specific primers yielded a 122-bp fragment
      from goats' milk DNA, whereas no amplification signal was obtained in sheep's,
      cows', and water buffaloes' milk DNA. Polymerase chain reaction analysis of raw
      and heat-treated milk binary mixtures of sheep/goat enabled the specific
      detection of goats' milk with a sensitivity threshold of 0.1%. This study
      demonstrates the usefulness of the proposed polymerase chain reaction assay for
      authentication of milk products in routine analysis.

PMID- 16107401
TI  - Determination of the heat stability profiles of concentrated milk and milk
      ingredients using high resolution ultrasonic spectroscopy.
AB  - In the present work, we used high resolution ultrasonic spectroscopy for the
      analysis of heat coagulation process in milks. Two skim milks recombined from
      powder samples differing by their preheating treatments as well as dairy
      ingredients (phosphocasein, whey protein isolate, and a milk model) were
      monitored while submitted to a temperature of 120 degrees C. Three stages in the
      precoagulation and coagulation processes can be distinguished in the ultrasonic
      velocity and attenuation profiles. The first stage shows a very sharp decrease in
      ultrasonic velocity and increase in ultrasonic attenuation. This could be
      attributed to fast denaturation and aggregation of whey proteins and
      precipitation of calcium phosphate. In the second stage, small changes in
      ultrasonic velocity are observed, the rate of which depends on the nature and pH
      of the samples. In the third stage, a sharp decrease in ultrasonic velocity and
      attenuation is recorded for all samples, which corresponds to the coagulation and
      formation of the gel network. After coagulation, a very small change in
      ultrasonic velocity and attenuation was observed. From the ultrasonic
      measurements, we determined the heat stability vs. pH profiles of the different
      samples studied. The observed ultrasonic attenuation profiles were also
      interpreted in terms of changes in the size of casein micelles and coagulation
      processes.

PMID- 16107402
TI  - Low pressure CO2 storage of raw milk: microbiological effects.
AB  - The effects of holding raw milk under carbon dioxide pressures of 68 to 689 kPa
      at temperatures of 5, 6.1, 10, and 20 degrees C on the indigenous microbiota were
      investigated. These pressure-temperature combinations did not cause precipitation
      of proteins from the milk. Standard plate counts from treated milks demonstrated
      significantly lower growth rate compared with untreated controls at all
      temperatures, and in some cases, the treatment was microcidal. Raw milk treated
      with CO2 and held at 6.1 degrees C for 4 d exhibited reduced bacterial growth
      rates at pressures of 68, 172, 344, and 516 kPa; and at 689 kPa, demonstrated a
      significant loss of viability in standard plate count assays. The 689-kPa
      treatment also reduced gram-negative bacteria and total Lactobacillus spp. The
      time required for raw milk treated at 689 kPa and held at 4 degrees C to reach
      4.30 log10 cfu/mL increased by 4 d compared with untreated controls. Total
      coliform counts in the treated milk were maintained at 1.95 log10 cfu/mL by d 9
      of treatment, whereas counts in the control significantly increased to 2.61 log10
      cfu/mL by d 4 and 2.89 log10 cfu/mL by d 9. At d 8, Escherichia coli counts had
      not significantly changed in treated milk, but significantly increased in the
      control milk. Thermoduric bacteria counts after 8 d were 1.32 log10 cfu/mL in
      treated milk and 1.98 log10 cfu/mL in control milk. These data indicated that
      holding raw milk at low CO2 pressure reduces bacterial growth rates without
      causing milk protein precipitation. Combining low CO2 pressure and refrigeration
      would improve the microbiological quality and safety of raw milk and may be an
      effective strategy for shipping raw single strength or concentrated milk over
      long distances.

PMID- 16107403
TI  - Effect of anticoagulant and storage conditions on bovine nonesterified fatty acid
      and beta-hydroxybutyrate concentrations in blood.
AB  - The objective of this study was to determine if nonesterified fatty acid (NEFA)
      and beta-hydroxybutyrate (BHBA) concentrations were affected by anticoagulants or
      gel and clot activator tubes (serum separator tubes, SST), storage of samples as
      whole blood, separated plasma or serum at 24 degrees C or 4 degrees C for 24 to
      72 h, or storage as serum at -40 degrees C for 1 mo. Blood was collected from
      dairy cows into EDTA, heparin, nonanticoagulant tubes, and SST, and analyzed
      immediately to obtain baseline NEFA and BHBA concentrations. Portions were stored
      as whole blood or separated plasma or serum at 4 or 24 degrees C and assayed
      daily for 24 (whole blood) and 72 (separated samples) h. Serum samples were
      frozen at -40 degrees C and assayed at 24 h or weekly for 1 mo. Baseline NEFA
      concentrations were unaffected by anticoagulants; however, they were
      significantly higher in SST compared with nonanticoagulant tubes. Concentrations
      of NEFA were stable in all samples at 4 degrees C, whereas they sequentially
      increased from 24 to 48 h at 24 degrees C. Changes were more dramatic in
      heparinized samples. Serum could be stored frozen for up to 1 mo with minimal
      changes in NEFA concentrations. Concentrations of BHBA were stable under all
      conditions evaluated. Our results indicated that blood for NEFA testing should be
      collected into EDTA or nonanticoagulant tubes (but not SST), separated promptly
      from cells, and maintained at 4 degrees C until analysis.

PMID- 16107404
TI  - Short communication: Short-day photoperiod during the dry period decreases
      expression of suppressors of cytokine signaling in mammary gland of dairy cows.
AB  - Suppressors of cytokine signaling (SOCS) are induced by prolactin and act through
      negative feedback to inhibit cytokine signaling. We hypothesized that lower
      prolactin concentrations in cows exposed to short-day photoperiod (SD; 8 h
      light:16 h dark) lead to decreased expression of SOCS, which mediate the effects
      of SD on mammary proliferation during the dry period. Multiparous Holstein cows
      were dried off 60 d before expected calving and were assigned to long-day
      photoperiod (LD; 16 h light:8 h dark) or SD during the dry period. Mammary
      biopsies were obtained at -40, -20, -10, and +10 d relative to expected calving,
      and expression of SOCS-1, SOCS-2, SOCS-3, and cytokine-inducible SH2-containing
      protein (CIS) mRNA was assessed by real-time, quantitative, reverse transcription
      PCR. Expression of all SOCS increased over time and expression of SOCS-3, SOCS-2,
      and CIS mRNA was lower in mammary gland of SD cows. These data suggest that lower
      SOCS expression in cows exposed to SD during the dry period may enhance prolactin
      signaling to the mammary gland, thereby augmenting mammary development during
      pregnancy and milk production in the subsequent lactation. Changes in SOCS
      expression during pregnancy and lactation imply that SOCS may regulate mammary
      gland development and function in dairy cows.

PMID- 16107405
TI  - Antimicrobial susceptibility and coagulase gene typing of Staphylococcus aureus
      isolated from bovine clinical mastitis cases in Turkey.
AB  - The objectives of this study were to determine antimicrobial resistance patterns
      of Staphylococcus aureus strains isolated from bovine clinical mastitis cases and
      to subtype the strains by polymerase chain reaction (PCR) technique based on
      coagulase gene polymorphism. Two hundred sixty-five S. aureus isolates collected
      from individual animals in different herds (n = 235) from 1995 to 2004 were
      tested for susceptibility to penicillin, ampicillin, amoxicillin-clavulanate,
      oxacillin, oxytetracycline, enrofloxacin, kanamycin-cephalexin, and trimethoprim
      sulfamethoxazole using the agar disc diffusion test. Strains were also tested for
      beta-lactamase production. A total of 29.8% of the strains were susceptible to
      all antimicrobial agents tested. The highest resistance was observed in 63.3% of
      the strains against beta-lactam antibiotics, penicillin and ampicillin.
      Oxytetracycline resistance was observed in 27.9% of the strains, either alone or
      in combination with beta-lactams. No resistance was detected for amoxicillin
      clavulanate, oxacillin, enrofloxacin and kanamycin-cephalexin. beta-Lactamase
      production and resistance to beta-lactam antibiotics were usually correlated.
      Resistance against beta-lactams increased from 43.5% in 1995 to 58 to 77% from
      1999 to 2004. One hundred twenty-five strains were examined for coagulase gene
      polymorphism. The isolates were subtyped into 4 types by coagulase gene-based
      PCR. A predominant 1000-bp PCR product was observed in 60.8% of the isolates
      typed. The results indicate that a few coagulase gene types of S. aureus are
      responsible for the majority of bovine clinical mastitis cases in one province of
      Central Anatolia region, Turkey.

PMID- 16107406
TI  - Trends and seasonality of reproductive performance in Florida and Georgia dairy
      herds from 1976 to 2002.
AB  - Trends in reproductive performance from 1976 to 2002 were studied for dairy farms
      located in Florida and Georgia using 2,897,517 Dairy Herd Improvement Association
      lactation records of Holstein cows. One-half of the 1552 herds in the final
      edited records had measures for at least 8 yr. Measures of reproductive
      performance changed significantly over time. Days to first service increased from
      a low of 84 d in 1983 to 104 d in 2001. Cows that calved during spring had 9.2
      (1983) to 33.2 (1999) more days to first service than cows that calved during
      fall. Annual pregnancy rates (PR) for 71 to 364 d since last calving (DSC; PR(71
      364)) decreased from 21.6% in 1977 to 1979, to 12% in 2000 to 2002. The greatest
      PR(71-364) was observed during winter and the lowest during summer (15.8 vs. 5.6%
      in 2002, respectively). The absolute difference between PR(71-364) during winter
      and summer remained similar over time at 11 percentage units. Pregnancy rates in
      the early stages since calving (71 to 133 d) showed greater decreases over time
      than PR in the later stages since calving. From 1998 to 2002, PR in the later
      stages since calving (134 to 364 d) was on average 11.5%. Pregnancy rate from 71
      to 133 DSC remained greater (13.4%). In the winter, the decrease in PR(71-364)
      was primarily due to a large decrease in PR(71-91). Average days to conception
      increased from a low of 121 in 1982 to a high of 167 in 1998. The average
      difference between cows that calved during spring and fall increased from 22 d in
      1976 to 47.5 d in 1986, but remained constant at 39.1 d from 1985. Average
      calving interval increased from 399 d in 1976 to 429 d in 2000. Average days dry
      between 1976 and 2001 remained similar at 69 d. Days to culling of nonpregnant
      cows after 182 DSC increased from 341 in 1983 to 415 in 1998. Season of calving
      had no clear association with average days to culling. The last milk yield
      recorded less than 1 mo before culling of nonpregnant cows after 182 DSC
      decreased by DSC to approximately 1 yr since calving, after which it remained
      constant at an average of 12.3 kg/d. The last known milk yield of cows culled
      during spring was 1.6 kg/d greater than those culled during fall. This difference
      did not significantly change over time. Increases in actual 305-d herd milk
      production were associated with increased days to first service, days to
      conception, and calving interval, but also with increased PR(71-364). Herd size
      did not have a clear association with reproductive efficiency.

PMID- 16107407
TI  - Hoof pathologies influence kinematic measures of dairy cow gait.
AB  - To explore how hoof pathologies affect the gait of dairy cattle, we studied gait
      profiles of cows with no visible injuries (n = 17), sole lesions (n = 14), and
      sole ulcers (n = 7). Video recordings of dairy cows were digitized using motion
      analysis software to calculate 6 stride variables for each hoof. Compared with
      cows with sole ulcers, healthy cows walked faster (1.11 +/- 0.03 vs. 0.90 +/-
      0.05 m/s, mean +/- SEM), had shorter stride durations (1.26 +/- 0.03 vs. 1.48 +/-
      0.05 s), and longer strides (139.5 +/- 2.1 vs. 130.0 +/- 3.2 cm). Percentage of
      triple support in the gait cycle (time when cattle were supported by 3 legs) more
      than doubled for cows with sole ulcers compared with healthy cows (42 vs. 18%).
      Gait differences were likely due to cows reducing the load on an affected leg.
      Few differences were detected between healthy cows and those with sole lesions,
      perhaps because of variation in number, severity, and location of injuries.
      Kinematic gait analysis is a promising approach in understanding how hoof
      pathologies affect dairy cow gait.

PMID- 16107408
TI  - Changes in freezing point of blood and milk during dehydration and rehydration in
      lactating cows.
AB  - We studied the influence of short-term changes in water intake in 4 lactating
      Holstein cows on diurnal fluctuation of packed cell volume (PCV), freezing point
      of blood (FPblood), freezing point of milk (FPmilk), and the relationship between
      changes in FPblood and FPmilk. The experiment lasted 108 h and was divided into 3
      periods: 1) control (38 h); 2) dehydration/rehydration with 4 consecutive 12-h
      sequences: 8 h without water, 0.5-h access to water, 1.5 h without water, and 2-h
      access to water; and (3) 22 h for reconstitution. Cows were milked at 12-h
      intervals. Blood was sampled from the jugular vein hourly throughout the
      experiment, and at 0, 15, 30, 60, 90, 120, 150, 180, 210, and 240 min after
      initiated rehydration following the 8-h dehydration sequences. Intakes of free
      water and water in feed were recorded every hour. The PCV was negatively affected
      by water intake within the hour before sampling. Dehydration lowered FPblood
      steadily, whereas FPblood increased by 0.024 degrees C within 30 min following a
      large water intake in the rehydration period. The FPblood was not significantly
      influenced by actual water intake, but was highly correlated with the available
      water pool at time of blood sampling. The FPmilk correlated positively with the
      FPblood collected 1 h before milk sampling, indicating a delay in the transfer of
      water from plasma to milk. In summary, FPblood and FPmilk decrease during
      dehydration and increase during rehydration. Rehydration following a long
      dehydration period caused an increase in FPmilk within 1 h, but not above the
      initial level for FPmilk of the cow.

PMID- 16107409
TI  - Quarter health, milking interval, and sampling time during milking affect the
      concentration of milk constituents.
AB  - Eleven Danish Holstein cows were used to examine the effects of quarter health
      (healthy vs. unhealthy), milking interval (12 vs. 6 h), and sampling time during
      milking on the concentration of 8 milk constituents [acetone, beta
      hydroxybutyrate (BHBA), N-acetyl-beta-D-glucosaminidase (NAGase), somatic cell
      count (SCC), urea, fat, protein, and lactose]. The selection criterion was that
      each cow should have 2 or 3 healthy and 1 or 2 unhealthy quarters. Foremilk was
      collected before attaching the teat cups of the milking machinery, and
      thereafter, milk samples were collected automatically from each quarter every 45
      s during milking. Compared with milk from healthy quarters, milk from unhealthy
      quarters had a higher concentration of BHBA, NAGase, SCC, and protein during the
      entire milking, whereas urea was higher in the last part of the milking process.
      Healthy quarters had a higher content of acetone and lactose during the whole
      milking, whereas fat was higher in the first part of the milking process. When
      the cows were milked at the 6-h interval, all milk constituents except lactose
      and protein were higher during the whole (NAGase, SCC, and urea) or part of the
      milking (acetone, BHBA, and fat) compared with when cows were milked at the 12-h
      interval. Lactose was higher in the first part of the milking at the 12-h
      compared with the 6-h interval, whereas protein was not affected by milking
      interval. beta-Hydroxybutyrate, NAGase, SCC, and fat increased during the milking
      process, whereas acetone, urea, protein, and lactose decreased. Foremilk was
      remarkably different for all constituents, except acetone, and should not be used
      as a representative milk sample to achieve the true level of a milk constituent.
      If these milk constituents are to be used in an inline management system, these
      effects should be taken into account.

PMID- 16107410
TI  - Tie-stall design and its relationship to lameness, injury, and cleanliness on 317
      Ontario dairy farms.
AB  - The objective of this study was to identify relationships between tie-stall
      design and selected cow-based injury, lameness, and cleanliness measurements. All
      lactating dairy cows (n = 17,893) from 317 Ontario tie-stall dairy farms were
      evaluated once between March and September 2003. Stall dimensions were recorded
      and cows were scored for neck and hock lesions, broken tails, back arch, hind
      claw rotation, and udder and hind limb cleanliness. Neck lesions were
      significantly associated with tie-rail height. Hock lesions were positively
      associated with presence of an electric trainer and hind limb and udder
      cleanliness and negatively associated with tie-chain length. A negative
      association was found between broken tails and tie-rail height and a positive
      association between broken tails and udder and hind limb cleanliness. As mean
      stall length increased, fewer cows had hind-claw rotation. Having more dirty cows
      was associated negatively with stall length and chain length, and positively
      associated with the presence of an electric trainer. Proportion of cows with
      clean udders increased with the percentage of cows with clean hind limbs and with
      tie-rail height. As the prevalence of clean udders increased the prevalence of
      broken tails decreased. This study provides insight into how tie-stall dimensions
      may influence aspects of dairy cow welfare. Application of these principles could
      improve tie-stall design.

PMID- 16107411
TI  - Characterization of Staphylococcus aureus isolates recovered from bovine mastitis
      in Rio de Janeiro, Brazil.
AB  - Phenotypic characteristics, antimicrobial susceptibility, and genetic
      relationships were analyzed in 107 Staphylococcus aureus isolates recovered from
      cows with subclinical mastitis in Southeastern Brazil. Thirteen different
      biochemical patterns were detected among isolates. A predominant pattern
      represented by about 54% of the isolates was distributed among several herds.
      Isolates of distinct phenotypic profiles were also detected within a herd.
      Susceptibility to ampicillin, cefotaxime, cephalotin, chloramphenicol,
      erythromycin, gentamycin, kanamycin, nitrofurantoin, norfloxacin, ofloxacin,
      oxacillin, penicillin, rifampin, sulfamethoxazole-trimethoprim, tetracycline,
      trimethoprim, and vancomycin, determined by the disk diffusion method, was
      observed in 44.9% of isolates. On the other hand, 55.1, 7.4, and 2.8% of the
      strains were resistant to ampicillin/penicillin, tetracycline, and erythromycin,
      respectively. Genetic diversity was analyzed by pulsed-field gel electrophoresis
      using SmaI as the restriction enzyme. All isolates could be typed by pulsed-field
      gel electrophoresis, which identified 16 types and 24 subtypes. Type A and its
      subtypes comprised 54.2% of all isolates and were recovered from 6 of the 9 herds
      analyzed. Other types and subtypes were also found in multiple herds. Although
      multiple types and subtypes were found within a specific herd, a predominant type
      was frequently observed.

PMID- 16107412
TI  - Fatty acid profiles associated with microbial colonization of freshly ingested
      grass and rumen biohydrogenation.
AB  - Two in situ studies were conducted to examine the use of odd-chain fatty acid
      profiles to study microbial colonization of freshly ingested herbage in the rumen
      as well as fatty acid biohydrogenation. In the first study, fresh perennial
      ryegrass was subjected to a range of sample preparation methods before incubation
      in the rumen for 2 or 7 h. In the second study, fresh perennial ryegrass was
      chopped into 1-cm lengths and incubated in polyester bags in the rumen for 2, 8,
      and 24 h. After removal of bags from the rumen, 4 different washing methods,
      ranging from manual squeezing to machine washing, were applied. Fatty acids were
      extracted from washed residues and determined, as methyl esters, by gas
      chromatography. The main odd-chain fatty acids (with the exception of anteiso
      C(15:0)) were not found in fresh grass and were useful markers of the effects of
      incubation time, sample preparation method, and washing method on microbial
      colonization/contamination. The concentration of these and other odd-chain fatty
      acids increased with incubation time in both studies. The results indicate rapid
      and continued microbial colonization of freshly ingested forages, although
      patterns of odd-chain fatty acids did not reveal any further information about
      the types of bacteria-colonizing herbage. Principal component, biplot analysis
      provided a useful overall description of the processes of microbial colonization
      and degradation of plant fatty acids on fresh herbage incubated in the rumen.
      Bolus formation during mastication and ingestion results in extensive damage to
      herbage; none of the techniques (cutting, crushing, and drying/grinding)
      investigated in this work was able to replicate the effects of bolus formation in
      the animal. The study provided further evidence of loss of unfermented feed
      particles through polyester bag pores, especially when feeds are dried and
      ground. Biohydrogenation of the polyunsaturated fatty acids of fresh herbage was
      used principally by solid-associated bacteria to enable them to take up high
      levels of trans-11 C(18:1) and C(18:0) fatty acids. Although trans-11 C(18:1) was
      strongly associated with bacterial markers (odd- and branched-chain fatty acids),
      its precursor (cis-9, trans-11 C(18:2)) was not associated with bacterial
      variation, suggesting that its production in the rumen under these conditions was
      mainly extracellular.

PMID- 16107413
TI  - Analysis of alpha-linolenic acid biohydrogenation intermediates in milk fat with
      emphasis on conjugated linolenic acids.
AB  - Ruminal biohydrogenation of alpha-linolenic acid is not fully understood compared
      with that of linoleic acid. Some hypothetical intermediates, that is, conjugated
      isomers of alpha-linolenic acid (cis-9,trans-11,cis-15 and cis-9,trans-13,cis-15
      18:3) have never been reported to occur in ruminant fat. Therefore, milk fat was
      analyzed using a combination of techniques to characterize alpha-linolenic acid
      biohydrogenation intermediates. Tandem off-line argentation thin-layer
      chromatography and high-resolution gas-liquid chromatography using a 120-m highly
      polar, open tubular capillary column coated with 70% cyanoalkyl polysiloxane
      equivalent material was used for quantification. Structural characterization of
      fatty acids was achieved by gas-chromatography mass-spectrometry after synthesis
      of specific azo-derivatives. This study confirmed that minute amounts of alpha
      linolenic acid biohydrogenation intermediates are present in milk fat. Routes
      involved in biohydrogenation of linoleic and alpha-linolenic acids in the rumen
      and subsequent endogenous metabolism of related biohydrogenation products are
      discussed.

PMID- 16107414
TI  - Effects of perennial ryegrass cultivars on intake, digestibility, and milk yield
      in dairy cows.
AB  - The effects of 8 diploid perennial ryegrass (Lolium perenne L.) cultivars on dry
      matter (DM) intake, DM digestibility, and milk yield (MY) of dairy cows were
      evaluated in the summer of 2000 and 2001. Each summer, herbage was harvested
      daily and stall-fed to 12 dairy cows during six 2-wk periods. Six cultivars were
      fed in 3 periods (1, 3, and 5) according to a double 3 x 3 Latin square design.
      In the other periods (2, 4, and 6), 2 cultivars were fed in a repeated
      measurement design. Herbage mass and leaf blades in the sward canopy varied among
      cultivars, but differences were not consistent between years. The largest
      differences in herbage composition were found in water-soluble carbohydrate
      content, followed by crude protein content. only small differences were found in
      the neutral detergent fiber (NDF) content. A higher water-soluble carbohydrate
      content was found in 2 cultivars in both years, whereas ranking of cultivars in
      crude protein and NDF content was not consistent with years. Dry matter intake
      and MY were not affected by cultivar. In both years, DM digestiblity was high
      (>77%), with very small differences among cultivars in 2000 (<0.5%) and larger
      differences in 2001 (up to 4%). This was associated with a delayed heading date
      in 2001, resulting in larger differences in leaf blades and NDF content among
      cultivars. It may be concluded that the 8 cultivars used in our experiments do
      not provide grass breeders with encouraging evidence to include selection
      criteria for an increased DM intake, DM digestibility, and MY in their grass
      breeding schemes.

PMID- 16107415
TI  - Prepartum intake, postpartum induction of ketosis, and periparturient disorders
      affect the metabolic status of dairy cows.
AB  - Nutritional management during the dry period may affect susceptibility of cows to
      metabolic and infectious diseases during the periparturient period. Thirty-five
      multiparous Holstein cows were used to determine the effect of prepartum intake,
      postpartum induction of ketosis, and periparturient disorders on metabolic
      status. Cows were fed a diet from dry-off to parturition at either ad libitum
      intake or restricted intake [RI; 80% of calculated net energy for lactation (NEL)
      requirement]. After parturition, all cows were fed a lactation diet. At 4 d in
      milk (DIM), cows underwent a physical examination and were classified as healthy
      or having at least one periparturient disorder (PD). Healthy cows were assigned
      to the control (n = 6) group or the ketosis induction (KI; n = 9) group. Cows
      with PD were assigned to the PD control (PDC; n = 17) group. Cows in the control
      and PDC groups were fed for ad libitum intake. Cows in the KI group were fed at
      50% of their intake on 4 DIM from 5 to 14 DIM or until signs of clinical ketosis
      were observed; then, cows were returned to ad libitum intake. During the dry
      period, ad libitum cows ate more than RI cows; the difference in intake resulted
      in ad libitum cows that were in positive energy balance (142% of NEL requirement)
      and RI cows that were in negative energy balance (85% of NEL requirement).
      Prepartum intake resulted in changes in serum metabolites consistent with plane
      of nutrition and energy balance. Prepartum intake had no effect on postpartum
      intake, serum metabolites, or milk yield, but total lipid content of liver at 1 d
      postpartum was greater for ad libitum cows than for RI cows. The PD cows had
      lower intake and milk yield during the first 4 DIM than did healthy cows. During
      the ketosis induction period, KI cows had lower intake, milk yield, and serum
      glucose concentration but higher concentrations of nonesterified fatty acids and
      beta-hydroxybutyrate in serum as well as total lipid and triacylglycerol in liver
      than did control cows. Cows with PD had only modest alterations in metabolic
      variables in blood and liver compared with healthy cows. The negative effects of
      PD and KI on metabolic status and milk yield were negligible by 42 DIM, although
      cows with PD had lower body condition score and BW. Prepartum intake did not
      affect postpartum metabolic status or milk yield. Periparturient disorders and
      induction of ketosis negatively affected metabolic status and milk yield during
      the first 14 DIM.

PMID- 16107416
TI  - Genetic and phenotypic parameter estimates of total and partial lifetime traits
      for dairy ewes.
AB  - A data file with 11,547 lactations for 2602 Spanish Churra ewes, daughters of 100
      sires and 2179 dams, was used to estimate genetic and phenotypic parameters of
      total and partial lifetime traits with a multiple-trait animal model using REML.
      These ewes first lambed between 1992 and 1998 and belonged to 27 flocks enrolled
      in the nucleus scheme of the breed. The study took into account 4 life span
      traits, 2 productive traits, and 2 reproductive traits. Lifetime revenues from
      milk and lambs were calculated. Daily traits for both milk and revenues of
      lifetime, productive life, and useful life were also calculated. Partial lifetime
      traits were considered for the first 3 parities. The model included flock and
      birth year within flock as fixed effects and animal as a random effect. Both
      fixed effects contributed significantly to variation of all total lifetime
      traits. Milk production level was included in the model as a covariable to adjust
      life span traits. Heritability estimates for life span traits were low (0.02 to
      0.06), indicating few possibilities for direct genetic selection. Genetic and
      phenotypic correlations among life span traits averaged 0.90 and 0.87,
      respectively. Heritabilities for daily milk and revenue traits were always higher
      than those for their corresponding lifetime traits. Heritability for milk yield
      per day of useful life was 0.25 (+/-0.04). Heritability estimates for partial
      lifetime performance traits increased notably when more parities were included
      (from the first parity to the first 3 parities). Their genetic and phenotypic
      correlations with total lifetime traits also increased gradually when more
      information was considered. These results indicate that possibilities for early
      genetic selection for some lifetime traits are not totally excluded.

PMID- 16107417
TI  - Genetic analysis of clinical mastitis, milk fever, ketosis, and retained placenta
      in three lactations of Norwegian red cows.
AB  - The objectives were to infer heritability and genetic correlations between
      clinical mastitis (CM), milk fever (MF), ketosis (KET), and retained placenta
      (RP) within and between the first 3 lactations and to estimate genetic change
      over time for these traits. Records of 372,227 daughters of 2411 Norwegian Red
      (NRF) sires were analyzed with a 12-variate (4 diseases x 3 lactations) threshold
      model. Within each lactation, absence or presence of each of the 4 diseases was
      scored based on the cow's health recordings. Each disease was assumed to be a
      different trait in each of the 3 lactations. The model for liability had trait
      specific effects of year-season of calving and age of calving (first lactation)
      or month-year of calving and calving interval (second and third lactations), herd
      5-yr, sire of the cow, and a residual. Posterior means of heritability of
      liability in first, second, and third lactations were 0.08, 0.07, and 0.07,
      respectively, for CM; 0.09, 0.11, and 0.13 for MF; 0.14, 0.16, and 0.15 for KET,
      and 0.08 in all 3 lactations for RP. Posterior means of genetic correlations
      between liability to CM, MF, KET, and RP, within disease between lactations,
      ranged from 0.19 to 0.86, and were highest between KET in different lactations.
      Correlations involving first lactation MF were low and had higher standard
      deviations. Genetic correlations between diseases were low or moderate (from 
      0.10 to 0.40), within as well as between lactations; the largest estimates were
      for MF and KET, and the lowest involved MF or KET and RP. Positive genetic
      correlations between diseases suggest that some general disease resistance factor
      with a genetic component exists. Trends of average sire posterior means by birth
      year of daughters were used to assess genetic change, and the results indicated
      genetic improvement of resistance to CM and KET and no genetic change for MF and
      RP in the NRF population.

PMID- 16107418
TI  - Genetic parameters for female fertility traits and a fertility index in Spanish
      dairy cattle.
AB  - Genetic correlations among female fertility traits (linear and binary) were
      estimated using 225,085 artificial insemination records from 120,713 lactations
      on 63,160 Holstein cows. Fertility traits were: calving interval, days open, a
      linear transformation of days open, days to first insemination, interval between
      first and last insemination, number of inseminations per service period,
      pregnancy within 56 and 90 d after first insemination, and success in first
      insemination. A bivariate animal model was implemented using Bayesian methods in
      the case of binary traits. Low heritabilities (0.02 to 0.06) were estimated for
      these fertility traits. Strong genetic correlations (0.89 to 0.99) were found
      among traits, except for days to first service, where the genetic correlation
      with other fertility traits ranged from -0.52 to -0.18 for binary traits, and
      from 0.50 to 0.82 for days to first service, calving interval, and days open.
      Four fertility indices were proposed utilizing information from insemination
      records; these indices combined one indicator of the beginning of the service
      period and one indicator of conception rate. Two additional indices used
      information from the milk-recording scheme, including calving interval and a
      linear transformation of days open. The fertility index composed of days to first
      service and pregnancy within 56 d achieved the highest genetic gain for reducing
      fertility cost, reducing days to first service, and reducing the number of
      inseminations per lactation ($8.60, -1.31 d, and -0.03 AI, respectively). This
      index achieved at least 15% higher genetic gain than obtained from indices with
      information from the milk recording scheme only (calving interval and days open).

PMID- 16107419
TI  - Prior (co)variances can improve multiple-trait across-country evaluations of
      weakly linked bull populations.
AB  - National genetic evaluation results for fore udder attachment from 9 Ayrshire
      populations were used to assess the impact of different uses of prior genetic
      correlations in multiple-trait across-country evaluations (MACE) on predicted
      international genetic merit. These Ayrshire populations were poorly connected;
      that is, 2% of the bulls had evaluations in 2 or more countries. Genetic
      correlations from the Holstein populations in the same countries were used as
      prior information to improve inferences of location parameters and international
      genetic merits. Fully Bayesian analyses using Gibbs sampling and computationally
      less demanding traditional MACE assuming a weighted average of prior and
      estimated Ayrshire genetic correlations were compared for 3 different prior
      degrees of belief and for different groups of bulls. Posterior means of genetic
      correlations estimated by Gibbs sampling were on average higher (+0.2) than those
      estimated by REML. Posterior heritabilities differed up to 0.2 units from those
      assumed in national genetic evaluations. Predicted genetic merit and
      international sire rankings of bulls with daughter information in the country of
      interest were not affected substantially by method of analysis and even less by
      varying prior degree of belief. Method of analysis had a larger impact on
      predicted genetic merit for bulls without daughter information in the country of
      interest. Here the average correlation between predicted genetic merit in
      different analyses ranged from 0.62 to 0.99. The predictive ability for young and
      randomly chosen bulls favored Bayesian MACE. The prior degree of belief did not
      have much impact on sire rankings and predictive ability, but intermediate prior
      degree of belief tended to perform best. All MACE analyses yielded nearly
      unbiased predictions. Traditional MACE assuming a simple weighted average of
      prior and estimated Ayrshire genetic correlations has been implemented by
      Interbull for routine international genetic evaluations.

PMID- 16107420
TI  - Short communication: Difficulties in estimating across-country genetic
      correlations for weakly linked bull populations.
AB  - Genetic correlations across 9 weakly linked bull populations were estimated with
      various models, methods, and data sets. Estimates of the same genetic correlation
      differed noticeably depending on estimation strategy (up to 1.03 units) for
      country-pairs with no or few direct genetic links. Differences in estimated
      genetic correlations decreased with an increasing number of genetic ties between
      countries, and, essentially, no differences were found between estimated genetic
      correlations based on 61 common bulls, regardless of the estimation strategy
      used.

PMID- 16107421
TI  - Principal components and factorial approaches for estimating genetic correlations
      in international sire evaluation.
AB  - The increasing number of participating countries and the lack of genetic links
      among some of them lead to statistical and computational difficulties in
      estimating the genetic (co)variance matrix needed for international sire
      evaluation of milk yield. Reparameterization using principal components or
      factorial approaches is proposed to exploit patterns in the genetic correlation
      matrix in order to reduce the number of parameters to be estimated without much
      loss of information. A 2-step approach was used. First, the genetic matrix
      between 8 or 9 "base" countries was used to determine a reduced number of
      principal components or factors. Then, the contributions of the remaining
      countries to these principal components or factors were computed. The resulting
      genetic correlations for the 18 countries were compared with the "reference"
      genetic correlations obtained with a classical model. The impact of using
      reparameterized genetic correlation matrices on breeding value prediction was
      investigated for both approaches. A better agreement between predicted breeding
      values and stability of their rankings was found when an approximate factor
      analysis was used, whatever the number of factors considered. The estimation of
      genetic correlations among 18 countries using an approximate factorial approach
      with 5 factors taken into account led to a reduction of the number of parameters
      to estimate from 171 to 80. The average absolute deviation of the correlations
      estimated with an approximate factorial approach from the "reference" genetic
      correlations was 0.014, which is considered very satisfactory in light of the
      computational ease.

PMID- 16107422
TI  - Genetic parameters of claw and foot disorders estimated with logistic models.
AB  - The primary aim of this study was to estimate heritabilities for different types
      of claw and foot disorders and the genetic relationship of disorders with milk
      yield and selected conformation traits by applying logistic models in Holstein
      dairy cattle. The study included data from 5634 Holstein cows kept on large-scale
      dairy farms in Eastern Germany. Dichotomous response variables were the presence
      or absence of the disorder in 2003. Cows that were present in herds for <6 wk in
      2003 were excluded from the analysis. Incidences, disregarding repeated
      measurements, for digital dermatitis (DD), sole ulceration (SU), wall disorder
      (WD), and interdigital hyperplasia (IH) in rear legs were 13.2, 16.1, 9.6, and
      6.3%, respectively. The herd effect was highly significant for all disorders.
      Incidences increased with increasing parities for SU and WD, but were highest
      among heifers for DD. High milk yield at the first 2 test d after calving was
      associated with a greater risk for claw and foot disorders in the same lactation.
      Estimates of heritability were 0.073 for DD, 0.086 for SU, 0.104 for WD, and
      0.115 for IH. Genetically, health problems appear to occur in clusters (i.e., a
      cow showing one disease has an increased genetic risk of showing another claw
      disease). This phenomenon was also observed between claw and foot disorders and
      the somatic cell score. Genetic correlations between milk yield in early
      lactation and disorders were 0.240 for DD, 0.057 for SU, 0.270 for WD, and 0.336
      for IH, indicating a physiological antagonism. Correlations between breeding
      values for claw and foot disorders of bulls and official breeding values for
      functional type traits were mostly favorable. Routine recording of claw data will
      offer a new chance to improve claw health within the population as was elaborated
      by different scenarios applying selection index procedures.

PMID- 16107423
TI  - Joint international evaluation of Milking Shorthorn dairy cattle for production
      traits.
AB  - Pedigree information and test-day records for the first 3 parities of Milking
      Shorthorn dairy cattle from 5 countries were analyzed. After editing, the data
      included 1,018,528 test-day records from 68,653 cows. A multiple-lactation random
      regression test-day model with Legendre polynomials of order 4 and a Bayesian
      method were used to estimate variance components for both single and multiple
      countries. Fixed effects included herd-test-day class and regressions on DIM
      within age at calving-parity-season of calving. Random effects included animal
      genetic, permanent environmental, and residual effects. Average daily
      heritabilities from single country analyses ranged from 0.33 to 0.47 for milk
      yield and from 0.37 to 0.45 for protein yield across lactations and countries.
      Common sires (66) and their daughters were identified for creating a connected
      data set for simultaneous (co)variance component estimation of milk yield across
      all 5 countries. Between-country genetic correlations were low, with values from
      0.08 to 0.46 and standard deviations from 0.08 to 0.12. Estimated breeding values
      for milk were generated for each animal using the same test-day animal model.
      Correlations among country estimated breeding values were higher than genetic
      correlations. Top 100 bull lists were generated on the scale of each country, and
      genetic progress was assessed. Future evaluation with increased genetic ties
      among countries may facilitate international comparison of Milking Shorthorns.

PMID- 16107424
TI  - Impact of maturity rate of daughters on genetic ranking of Holstein bulls.
AB  - If genetic evaluations are calculated with a single-trait repeatability model,
      evaluation changes may be attributed in part to bulls that have daughters that
      deviate considerably from the typical response to aging. Differences in maturity
      rate of bull daughters were examined to determine whether they influence change
      in bull evaluations. Standardized milk records for Holsteins that first calved
      between 1960 and 1998 were used to calculate 12 tailored predicted transmitting
      abilities (PTA) for each bull. Predicted transmitting abilities were tailored
      from combinations of 4 annual cut-off dates and 3 parities. Date screening
      selected cows first calving before January of 1996, 1997, 1998, or 1999. Parity
      screening selected milk records from the first 1, 2, or 3 parities. Therefore, 4
      evaluations (PTA1) included only first-parity records available for daughters and
      contemporaries prior to the respective years designated. Four more evaluations
      (PTA(1,2)) included the records from the first 2 parities for cows first calving
      prior to those same year cutoffs; likewise, the last 4 evaluations (PTA(1,2,3))
      included records from the first 3 parities. Stability of bull evaluations
      (standard deviations of differences as well as correlations between bull
      evaluations) across time was compared. Bulls born after 1984 with > or =500
      daughters were of interest because of the high precision of evaluations and
      recent activity. Tailored PTA of those bulls had more uniformity across years in
      mean records per daughter than did official USDA PTA. Standard deviation of
      differences in PTA1, PTA(1,2), and PTA(1,2,3) for milk between evaluation years
      1996 and 1997 were 28, 28, and 27 kg compared with 63 kg for official
      evaluations; similarly, between 1996 and 1999, SD were 36, 32, and 32 kg compared
      with 80 kg. Results suggested that a modification to the current evaluation model
      to account for maturity rate should reduce fluctuations in individual bull PTA
      across time and may improve accuracy of evaluations.

PMID- 16107425
TI  - Genetic evaluation of dairy cattle with test-day models with autoregressive
      covariance structures and with a 305-d model.
AB  - This study compared genetic evaluations from 3 test-day (TD) models with
      different assumptions about the environmental covariance structure for TD records
      and genetic evaluations from 305-d lactation records for dairy cows. Estimates of
      genetic values of 12,071 first-lactation Holstein cows were obtained with the 3
      TD models using 106,472 TD records. The compound symmetry (CS) model was a simple
      test-day repeatability animal model with compound symmetry covariance structure
      for TD environmental effects. The ARs and ARe models also used TD records but
      with a first-order autoregressive covariance structure among short-term
      environmental effects or residuals, respectively. Estimates of genetic values
      with the TD models were also compared with those from a model using 305-d
      lactation records. Animals were genetically evaluated for milk, fat, and protein
      yields, and somatic cell score (SCS). The largest average estimates of accuracy
      of predicted breeding values were obtained with the ARs model and the smallest
      were with the 305-d model. The 305-d model resulted in smaller estimates of
      correlations between average predicted breeding values of the parents and
      lactation records of their daughters for milk and protein yields and SCS than did
      the CS and ARe models. Predicted breeding values with the 3 TD models were highly
      correlated (0.98 to 1.00). Predicted breeding values with 305-d lactation records
      were moderately correlated with those with TD models (0.71 to 0.87 for sires and
      0.80 to 0.87 for cows). More genetic improvement can be achieved by using TD
      models to select for animals for higher milk, fat, and protein yields, and lower
      SCS than by using models with 305-d lactation records.

PMID- 16107426
TI  - Visual detection of technical success and effectiveness of teat cleaning in two
      automatic milking systems.
AB  - Technical success and effectiveness of teat cleaning and the management factors
      associated with them were evaluated in 9 automatic milking herds. In total, 616
      teats cleaned with a cleaning cup and 716 teats cleaned with rotating brushes
      were included. Technical success and the effectiveness of teat cleaning,
      including the location and nature of the dirt, were evaluated visually. On
      average, 79.9% of teat cleanings with a cleaning cup, and 85.0% of those cleaned
      with brushes succeeded technically; that is, the teat was correctly positioned in
      the cleaning device throughout the whole cleaning process. The difference between
      use of teat cups and brushes was significant. However, because technical success
      of teat cleaning is strongly dependent on herd characteristics, these results
      should be interpreted with caution. Factors associated with the technical success
      of teat cleaning with a cleaning cup were herd, days in milk, behavior of the
      cow, teat color, and teat location. For rotating brushes, behavior of the cow,
      teat location, udder and teat structure, and days in milk were associated with
      technical success. Excessive udder hair and technical failure of the automatic
      milking machine also caused a few technically unsuccessful teat cleanings with a
      cleaning cup. Teats with technically successful teat cleanings were evaluated for
      the effectiveness of teat cleaning. From originally dirty teats, the cleaning cup
      had a significant advantage over the brushes in the percentage of teats that
      became clean or almost clean during the cleaning process (79.8 vs. 72.9%). Teat
      orifices were least effectively cleaned compared with the teat barrel and apex.
      Bedding material (peat, sawdust, or straw) on the teat was cleaned almost
      completely. Factors associated with the effectiveness of teat cleaning were teat
      cleanliness before cleaning, herd, teat cleaning method, and teat condition. The
      variation among herds indicates the likelihood that herd management factors can
      be adjusted to improve milking hygiene. There is also a need to improve the
      precision and effectiveness of the teat cleaning mechanisms of automatic milking
      systems.

PMID- 16107427
TI  - Effect of feeding level pre- and post-puberty and body weight at first calving on
      growth, milk production, and fertility in grazing dairy cows.
AB  - The effect of feeding to achieve differential growth rates in Holstein-Friesian
      (HF; n = 259) and Jersey (n = 430) heifers on time to puberty and first lactation
      milk production was investigated in a 3 x 2 factorial design. Holstein-Friesian
      and Jersey calves were reared to achieve a BW of 100 and 80 kg, respectively, at
      100 d. At target weight, all calves were randomly allocated to one of 3 feeding
      treatments to achieve different growth rates. Holstein-Friesian and Jersey calves
      were fed fresh pasture to achieve average daily growth rates of 0.77, 0.53, or
      0.37 kg of BW/d (HF) and 0.61, 0.48, or 0.30 kg of BW/d (Jersey), respectively.
      Period 1 (prepubertal) was imposed until HF and Jersey treatment groups averaged
      200 and 165 kg of BW, respectively. Following period 1, HF and Jersey calves from
      each treatment group were randomly allocated to one of 2 feeding treatments to
      achieve average daily growth rates of 0.69 or 0.49 kg of BW/d (HF) and 0.58 and
      0.43 kg of BW/d (Jersey), respectively. Period 2 (postpubertal) was imposed until
      22 mo, when heifers were returned to their farms of origin. Body weight, body
      condition score, height, heart girth circumference (HGC), milk production, and
      fertility-related data were collected until the end of the third lactation. Time
      to reach puberty was negatively associated with level of feeding, and heifers
      attained puberty at the same BW (251 +/- 25.4 and 180 +/- 24.0 kg for HF and
      Jersey heifers, respectively). Heifers on high feed allowances during periods 1
      and 2 were heavier, taller, and had greater HGC than their slower grown
      counterparts until 39 mo of age when height and HGC measurements stopped. Body
      weight differences remained until 51 mo, when measurements ceased. High feed
      allowance during period 1 (prepubertal) did not affect milk production during the
      first 2 lactations, but did reduce milk production in lactation 3. It is possible
      that the expected negative effect of accelerated pre-pubertal growth was masked
      by greater calving BW, as BW-corrected milk yield declined in both breeds with
      increasing prepubertal feed allowance. Growth rate during period 2 was positively
      correlated with first lactation milk production. Milk yield increased 7% in first
      lactation heifers on the high feed allowance, which resulted in higher growth
      rate during period 2. Milk production during subsequent lactations was not
      affected. Results suggest that accelerated prepubertal growth may reduce mammary
      development in grazing dairy cows, but this does not affect milk production in
      early lactations because of superior size. Body weight at calving and
      postpubertal growth rate management are important in first lactation milk
      production, but do not affect milk production in subsequent lactations.

PMID- 16107428
TI  - Loss of genetic variation in geographically marginal populations of Atriplex
      tatarica (Chenopodiaceae).
AB  - BACKGROUND AND AIMS: Genetic variability was estimated for Atriplex tatarica from
      25 populations in the Czech Republic. Since its north-western range margin is in
      central Europe, a relationship between marginality and low within-population
      genetic diversity was tested in accordance with the Central-Marginal Model.
      METHODS: Population genetic diversity was expressed by assessing patterns of
      variation at 13 putatively neutral allozyme loci (comprising 30 putative alleles)
      within and between 25 natural populations of A. tatarica along a north-west-south
      east transect in the Czech Republic. KEY RESULTS: Atriplex tatarica is a species
      of human-made habitats with a mixed mating system and wide geographic
      distribution. Overall, A. tatarica displayed moderate levels of genetic diversity
      in comparison with other herbaceous plants. The percentage of loci that were
      polymorphic was 47.1%, with average values of 1.55, 0.151 and 0.155 for the
      average number of alleles per polymorphic locus (A), observed heterozygosity (Ho)
      and expected heterozygosity (He), respectively. There was only weak evidence of
      inbreeding within populations (FIS=0.031) and significant population
      differentiation (FST=0.214). Analysis of the data provides no evidence for
      isolation-by-distance for the whole study area. However, Mantel tests were highly
      significant for the marginal Bohemian region and non-significant for the central
      Moravian region. While northern populations of A. tatarica showed significantly
      lower allelic richness (A=1.462) than populations from the southern part of the
      study area (A=1.615), they did not differ in observed heterozygosity (Ho), gene
      diversity (HS), inbreeding within populations (FIS) or population differentiation
      (FST), despite generally lower values of particular genetic measurements in the
      marginal region. CONCLUSIONS: Genetic diversity, with the exception of allelic
      richness, was not significantly lower at the margins of the species' range. This,
      therefore, provides only weak support for the predictions of the Central-Marginal
      Model.

PMID- 16107429
TI  - Influence of growth hormone on the craniofacial complex of transgenic mice.
AB  - Growth hormone (GH) secretion affects bone and cartilage physiology. This study
      investigated the effect of GH on the size of the craniofacial structures and
      their angular relationship. Three different models of mice with a genetically
      altered GH axis were used: GH excess (giant), dwarf GH antagonist (dwarf-Ant),
      and dwarf GH receptor knockout (dwarf-KO) mice. Each model was compared with the
      corresponding wild type (Wt). Five craniofacial distances were analysed:
      craniofacial length, upper face height, mandibular anterior height, mandibular
      ramus length, and mandibular corpus length. In addition, upper and lower incisor
      lengths and four angular relationships, nasal bone with cranial base, maxillary
      plane with cranial base, mandibular plane with cranial base, and the angle of the
      mandible, were determined. Data were analysed by one-way ANOVA. Craniofacial
      length, upper face height and mandibular corpus length were significantly
      increased in the giant mice and significantly reduced in the dwarf mice.
      Mandibular anterior height and mandibular ramus length were significantly
      affected in the dwarf-KO mice but not in the giant mice. The length of both the
      upper and lower incisors was significantly increased and reduced in the giant and
      dwarf-KO mice, respectively. In addition, the angle of the mandible was
      significantly increased in the giant mice and significantly reduced in the dwarf
      mice. It is concluded that GH plays a major role in the growth and development of
      the craniofacial complex by directly and indirectly modulating the size and the
      angular relationships of the craniofacial structures, including the incisor
      teeth.

PMID- 16107430
TI  - The broader impact of walking to school among adolescents: seven day
      accelerometry based study.

PMID- 16107431
TI  - Modelling the decline in coronary heart disease deaths in England and Wales, 1981
      2000: comparing contributions from primary prevention and secondary prevention.
AB  - OBJECTIVE: To investigate whether population based primary prevention (risk
      factor reduction in apparently healthy people) might be more powerful than
      current government initiatives favouring risk factor reduction in patients with
      coronary heart disease (CHD) (secondary prevention). DESIGN, SETTING, AND
      PARTICIPANTS: The IMPACT model was used to synthesise data for England and Wales
      describing CHD patient numbers, uptake of specific treatments, trends in major
      cardiovascular risk factors, and the mortality benefits of these specific risk
      factor changes in healthy people and in CHD patients. RESULTS: Between 1981 and
      2000, CHD mortality rates fell by 54%, resulting in 68,230 fewer deaths in 2000.
      Overall smoking prevalence declined by 35% between 1981 and 2000, resulting in
      approximately 29,715 (minimum estimate 20 035, maximum estimate 44,675) fewer
      deaths attributable to smoking cessation: approximately 5035 in known CHD
      patients and approximately 24,680 in healthy people. Population total cholesterol
      concentrations fell by 4.2%, resulting in approximately 5770 fewer deaths
      attributable to dietary changes (1205 in CHD patients and 4565 in healthy people)
      plus 2135 fewer deaths attributable to statin treatment (1990 in CHD patients,
      145 in people without CHD). Mean population blood pressure fell by 7.7%,
      resulting in approximately 5870 fewer deaths attributable to secular falls in
      blood pressure (520 in CHD patients and 5345 in healthy people) plus
      approximately 1890 fewer deaths attributable to antihypertensive treatments in
      people without CHD. Approximately 45,370 fewer deaths were thus attributable to
      reductions in the three major risk factors in the population: some 36 625 (81%)
      in people without recognised CHD and 8745 (19%) in CHD patients. CONCLUSIONS:
      Compared with secondary prevention, primary prevention achieved a fourfold larger
      reduction in deaths. Future CHD policies should prioritise population-wide
      tobacco control and healthier diets.

PMID- 16107433
TI  - Marginalized and socially integrated groups of IDUs in Hungary: potential bridges
      of HIV infection.
AB  - The discrepancy in HIV rates among Eastern and central European injecting drug
      users (IDUs) suggests that, in addition to risk behaviors, social contact
      patterns also play an important role. We identify two groups of IDUs in Budapest,
      Hungary, marginalized IDUs (M-IDUs) and socially integrated IDUs (SI-IDUs) and
      compare their HIV/hepatitis B virus (HBV)/hepatitis C virus (HCV) social and risk
      network characteristics, risk behaviors, and travel patterns. Between May 2003
      and January 2004, 29 nontreatment-recruited young IDUs in Budapest participated
      in ethnographic interviews and focus groups. The mean age was 23.6 years
      (SD=3.6); eight were female and two Roma/Gypsy. Most injected heroin (n=23)
      and/or amphetamines (n=10) in the past 30 days. M-IDUs had no legal employment,
      injected heroin and sniffed glue, and stopped using drugs in treatment/prison. SI
      IDUs had regular jobs or were students, injected heroin and sniffed cocaine, and
      stopped using drugs before exams/tests. Both M-IDUs and SI-IDUs shared injecting
      equipment on occasion and used condoms rarely. M-IDUs had a large social network
      of "buddies" and a small risk network of "friends". SI-IDUs had two separate
      large social networks of "buddies": a M-IDU and a non-IDU network; and a small
      risk network of "friends". Both groups reported monogamous sexual relationships.
      M-IDUs traveled within Hungary, whereas SI-IDUs traveled to Western Europe. If an
      HIV epidemic among IDUs in Hungary is not prevented, SI-IDUs may form a potential
      "bridge" of HIV infection between high-risk IDU populations and the low-risk
      general population, whereas M-IDUs may become cores of infection. Different
      approaches may be appropriate for M-IDUs and SI-IDUs to prevent HIV.

PMID- 16107434
TI  - Drug use, street survival, and risk behaviors among street children in Lahore,
      Pakistan.
AB  - There are an estimated 3,500-5,000 street children living on the streets of
      Lahore, Pakistan. A disproportionate number of these children use drugs and
      engage in survival sex as coping mechanisms. Since August, 2003, Project Smile
      provides mobile social and health services to street children 6 days a week in
      selected neighborhoods. This study utilizes data from Project Smile registration
      data on the program's initial clients (n=347). The study aimed to compare
      current, former, and nondrug users regarding their reasons for living on the
      streets, survival and coping mechanisms, and reasons for drug initiation. Of the
      total sample, 17.0% reported never having used drugs, 15.9% reported being former
      drug users, and 67.1% reported having used drugs in the month before
      registration. Participants were 96% boys with a median age of 13 years. The
      median length of living on the streets was 18 months, and 52.7% had ever been
      arrested by the police. Odd jobs, begging, and pickpocketing were the primary
      sources of reported income. Forty-eight percent reported ever having engaging in
      transactional sex, and 40% reported cutting themselves, primarily to cope with
      their anger. Variables that were significantly correlated with being a current
      drug user (vs. never) in the presence of other variables included: being 13 years
      or older [adjusted odds ratio (AOR)=3.0; 95% confidence interval (95% CI)=1.3
      7.0]; reporting a daily income > or =Rs 60 (AOR=2.7; 95% CI=1.1-6.4); having a
      history of arrest (AOR=3.3; 95% CI=1.3-8.3); wanting to return home (AOR=0.3; 95%
      CI=0.1-0.8); feeling hatred from the public (AOR=5.1; 95% CI=2.0-12.9); ever
      exchanging sex for food, shelter, drugs, or money (AOR=3.4; 95% CI=1.3-8.9); and
      ever having cut themselves (AOR=15.4; 95% CI=3.4-70.7). Drug use is a major
      coping mechanism among street children in Lahore and is associated with many
      behaviors. Targeted programs are needed to meet their special needs.

PMID- 16107435
TI  - International research and local authorities: interplay between research and
      police agendas in the field of drug abuse and AIDS.
AB  - International study of drug use and HIV derives much of its value from affording
      investigators opportunities to compare similar behaviors in contrasting cultural
      contexts. In these contrasting cultural contexts, people entrusted with
      conducting police work and minimizing crime have ways of conducting their
      business that may or may not interfere with research on illegal or socially
      disapproved behaviors. Two cases illustrate interactions between well-meaning
      researchers and local authorities. In both, investigations benefited from having
      laid groundwork for local endorsement of study activities. Research on marijuana
      smoking in Costa Rica enjoyed strong cooperation from the Ministry of Health, but
      not so strong from the Ministry of Security because of a fledgling office of
      Narcotics. Studies of HIV risk among injecting drug users (IDUs) in Valencia,
      Spain, encountered no problems with police but noted dangers of low drug
      enforcement. Five principles of preparing for international research may help
      investigators to anticipate some varieties of contextual obstructions to research
      outside the United States.

PMID- 16107436
TI  - HIV research within the global context. Proceedings of an international research
      conference, Miami Beach, Florida, USA, August 2004.

PMID- 16107437
TI  - CDC international HIV prevention research activities among injection drug users
      in Thailand and Russia.
AB  - The Centers for Disease Control and Prevention (CDC) has participated in
      collaborative HIV prevention research activities in injection drug users (IDUs)
      with the Bangkok Metropolitan Administration (BMA) in Bangkok, Thailand, from
      1995 to the present and with the Orel AIDS Center in Orel Oblast, Russia, from
      2001 to 2003. Studies in Bangkok have included an HIV prevention trial
      preparatory cohort from 1995 to 1998, a seroconverter cohort from 1998 to the
      present, a phase III trial of the AIDSVAX B/E gp120 HIV vaccine from 1999 to
      2003, and a phase II/III HIV prophylaxis trial with tenofovir scheduled to begin
      in 2005. Activities in Orel included a review of HIV surveillance data in 2001,
      focus group discussions and a case-control study with HIV-infected and 
      uninfected IDUs in 2001, a cross-sectional study with the female sex partners of
      male IDUs in 2002, and a community outreach intervention in 2002-2003. In
      Bangkok, 1,209 IDUs were enrolled in the preparatory cohort which revealed an HIV
      incidence of 5.8% per 100 person-years; 133 HIV-infected IDUs have been followed
      in the seroconverter cohort with >85% follow-up and HIV and tuberculosis care
      provided; 2,546 IDUs were enrolled in the HIV vaccine efficacy trial which was
      successfully completed with a follow-up rate of >95%, although the vaccine was
      not shown to be effective at reducing HIV incidence; and 1,600 IDUs will be
      enrolled in the daily tenofovir HIV prophylaxis trial in 2005. In Orel, initial
      focus group discussions and epidemiologic studies revealed low HIV knowledge and
      high rates of unsafe injecting and sexual practices among IDUs and their female
      sex partners; and educational campaigns and the community outreach intervention
      were developed and implemented. A steady decline in new HIV infections in IDUs
      was then observed in Orel in 2002-2003. CDC has participated in the conduct of
      successful collaborative HIV prevention research activities in Thailand and
      Russia over the past decade. The establishment of long-term relationships with in
      country public health and community partners has been instrumental in the success
      of these efforts.

PMID- 16107438
TI  - Community attitudes toward HIV prevention for injection drug users: findings from
      a cross-border project in southern China and northern Vietnam.
AB  - Success of HIV prevention projects for injection drug users (IDUs) depends on the
      support of the communities in which they are implemented. This article presents
      data from cross-sectional community surveys of HIV knowledge and attitudes toward
      peer-based HIV prevention interventions for injection drug users in a border area
      of Lang Son Province, Vietnam and Ning Ming County, Guangxi Province, China.
      Analysis of these surveys at baseline and 18 months reveals generally high or
      improving levels of HIV knowledge and positive attitudes toward the interventions
      in both Vietnam and China. Levels of knowledge and positive attitudes tended to
      be higher in Vietnam than in China. Interviews with staff and peer educators
      suggest that the project's community education efforts have increased support for
      the interventions and contributed to their smooth implementation. However, the
      community surveys also reveal some continuing deficits in HIV knowledge and
      understanding of the interventions, including perceptions that provision of new
      needles/syringes will result in increased drug use. Additional education,
      including dissemination of countervailing project data, is necessary to address
      these deficits and further increase community support for the interventions.

PMID- 16107439
TI  - HIV knowledge and risk behaviors among women in law enforcement in Bogota,
      Colombia: potential role as community educators.
AB  - As HIV infection is increasing among women, evaluation, prevention, and education
      campaigns need to target this vulnerable population. Because of their frequent
      and accepted contact with members of the community, female law officers, if
      knowledgeable, could be well suited to provide information/education related to
      HIV/STD transmission. A survey of HIV/AIDS knowledge and risk behaviors was
      administered to 120 law enforcement women (LEW) and 60 women from the general
      population (GPW) in Bogota, Colombia. LEW indicated a very high (90%)
      understanding of basic HIV knowledge. Although most (52%) of the LEW did not
      report high-risk behaviors, 29% indicated having unprotected sex during menses,
      and 17% had unprotected anal sex. This contrasts, however, with GPW, who were of
      similar age, but had a significantly higher prevalence (73%) of risky behaviors
      (P=.004). Moreover, 52% of the GPW reported having unprotected anal sex, and
      approximately half of this group (55%) indicated having unprotected sex during
      menses. Alcohol and drug users were also more prevalent in the GPW: 14%
      frequently used alcohol and 3% inhaled drugs during sexual encounters, contrasted
      to 2% of LEW reporting alcohol use. GPW were four times more likely than LEW, to
      engage in high-risk sexual practices [95% confidence interval (CI)=1.9-10.4,
      P=0.034]. Multivariate analyses indicated that alcohol and/or drug use were
      significantly associated with high-risk sexual practices [odds ratio (OR)=4.7,
      95% confidence intervals (CI)=1.3-18.4, P=.02). Improved educational HIV/AIDS
      programs are needed, particularly for women in the general population, who use
      alcohol/drugs during sexual encounters, which account, at least in part, for
      their high-risk behaviors. Women in law enforcement, who appear knowledgeable and
      exhibit safer behaviors, could be useful educators for GPW. Because of their
      professional role in the community, training for LEW in HIV/AIDS
      education/prevention programs should be considered.

PMID- 16107440
TI  - The CDRC principles of international health research.
AB  - The Comprehensive Drug Research Center (CDRC) at the University of Miami was
      established in the early 1970s. Through the decades, investigators from the CDRC
      have worked with investigators from several countries to establish joint research
      efforts. Countries often do not have the infrastructure or monetary resources to
      carry out research on their own. Collaborating with institutions in these
      countries to build a sustainable capacity for research is a worthwhile and
      satisfying endeavor, and it presents a method for initiating research and
      building the necessary research structures. However, working with other countries
      presents a unique set of challenges and ethical dilemmas. This article presents
      some of the specific challenges encountered in these research efforts and
      describes what we have done to resolve the problems and work more effectively and
      efficiently with foreign investigators.

PMID- 16107441
TI  - "Vivo para consumirla y la consumo para vivir" ["I live to inject and inject to
      live"]: high-risk injection behaviors in Tijuana, Mexico.
AB  - Injection drug use is a growing problem on the US-Mexico border, where Tijuana is
      situated. We studied the context of injection drug use among injection drug users
      (IDUs) in Tijuana to help guide future research and interventions. Guided in
      depth interviews were conducted with 10 male and 10 female current IDUs in
      Tijuana. Topics included types of drug used, injection settings, access to
      sterile needles, and environmental influences. Interviews were taped, transcribed
      verbatim, and translated. Content analysis was conducted to identify themes. Of
      the 20 IDUs, median age and age at first injection were 30 and 18. Most reported
      injecting at least daily: heroin ("carga", "chiva", "negra"), methamphetamine
      ("crico", "cri-cri"), or both drugs combined. In sharp contrast to Western US
      cities, almost all regularly attended shooting galleries ("yongos" or
      "picaderos") because of the difficulties obtaining syringes and police
      oppression. Almost all shared needles/paraphernalia ["cuete" (syringe),
      "cacharros" (cookers), cotton from sweaters/socks (filters)]. Some reported
      obtaining syringes from the United States. Key themes included (1) pharmacies
      refusing to sell or charging higher prices to IDUs, (2) ample availability of
      used/rented syringes from "picaderos" (e.g., charging approximately 5 pesos or
      "10 drops" of drug), and (3) poor HIV/AIDS knowledge, such as beliefs that
      exposing syringes to air "kills germs." This qualitative study suggests that IDUs
      in Tijuana are at high risk of HIV and other blood-borne infections.
      Interventions are urgently needed to expand access to sterile injection equipment
      and offset the potential for a widespread HIV epidemic.

PMID- 16107442
TI  - Developing an HIV intervention for indigent women substance abusers in the United
      States Virgin Islands.
AB  - As the HIV/AIDS epidemic continues to expand and penetrate new communities around
      the globe, risk reduction intervention initiatives must continue to evolve and
      adapt to new challenges and populations. This is especially true in the Caribbean
      Basin, where the feminization of the HIV epidemic is tied to a cultural milieu
      characterized by pervasive gender inequality. HIV intervention programs in the
      Caribbean must treat women's risks as a function of the social context,
      standards, and meanings of sexual behaviors and practices in the local community.
      As such, this article describes an initiative to develop an HIV prevention
      intervention protocol for the cultural context of substance abusing women in the
      US Virgin Islands. Through street-based survey research combined with focus
      groups and in-depth interviews with such "cultural insiders" as members of the
      substance-abusing target population, members of the local public health and
      social services system, and community leaders, a culturally sensitive HIV/AIDS
      protocol was developed which addresses the supports and barriers to risk
      reduction faced by substance abusing women in the Virgin Islands.

PMID- 16107443
TI  - Risk behaviors and HIV/AIDS prevention education among IDUs in drug treatment in
      Shanghai.
AB  - We estimated seroincidence of HIV, hepatitis B virus (HBV) and hepatitis C virus
      (HCV), and the prevalence of risk behaviors among injection drug users (IDUs) who
      accepted inpatient detoxification by 14-day methadone tapering treatment in the
      Shanghai Drug Abuse Treatment Center. We also evaluated the effect of an HIV/AIDS
      prevention education intervention on those IDUs. Data including demographic
      characteristics, HIV, HBV and HCV seroincidence, sexual and injection-related
      risk behaviors were collected from 101 IDUs. All subjects received HIV/AIDS
      prevention education during inpatient detoxification treatment. An HIV-knowledge
      questionnaire was used to evaluate the effects of this intervention. We found
      that risk behaviors, including unsafe sex and unclean injection practices, were
      common among the subjects. The seroincidence of HBV and HCV infection rates was
      56.4% and 46.5%, respectively, but no HIV-infected case was found among the
      subjects. After participating in the HIV/AIDS prevention intervention, subjects'
      scores (M+/-SD) on the HIV-knowledge questionnaire were significantly improved
      from baseline (97.29+/-7.42 vs. 31.1+/-12.1). Our study confirmed that IDUs in
      Shanghai are a high-risk population for blood borne diseases such as hepatitis B
      and hepatitis C and HIV. HIV/AIDS prevention education increased HIV knowledge,
      improved understanding of HIV prevention methods and changed attitudes toward
      HIV/AIDS. Therefore, HIV/AIDS prevention education should to be an important
      component of drug treatment.

PMID- 16107444
TI  - The process of research in international settings: from risk assessment to
      program development and intervention.
AB  - Although there are many challenges, international HIV prevention research and
      program evaluation are critical to advances in the health and welfare of people
      around the globe. While there is an increasing amount of literature describing
      outcomes of international prevention programs, there is sparse information
      regarding the process of developing and implementing international research. This
      brief report describes key elements in the development of collaborative
      international prevention research and programmatic implementation.

PMID- 16107445
TI  - Influence of partner participation on sexual risk behavior reduction among HIV
      positive Zambian women.
AB  - Sexual risk behavior interventions in sub-Saharan Africa focus predominantly on
      individual and couples counseling. This cognitive-behavioral group intervention
      was adapted from an urban US context to urban Zambia. Preliminary data analyses
      assessed the influence of partner participation on sexual risk behavior among HIV
      positive Zambian women. Female participants (n=180) attended four group
      intervention sessions and received sexual behavior skill training and male and
      female condoms; male partners (n=152) were randomly assigned to high- or low
      intensity gender-concordant group intervention sessions. Sexual risk behavior,
      strategies, attitudes, and knowledge were assessed at baseline, 6, and 12 months.
      At baseline, 19% of males reported using alcohol before sex, 10% reported using
      alcohol to cope, and negative coping was associated with sexual risk behavior. In
      contrast, 1% of women reported using alcohol before sex, and 15% used alcohol as
      an HIV-coping strategy. Consistent barrier use was reported by 48% of women and
      74% of men. After intervention, female high intensity participants reported
      higher rates of condom use (F=5.68, P=.02), more positive condom attitudes, safer
      sex intentions, and less alcohol use. These findings highlight the influence of
      male partners in implementation of effective risk reduction interventions.

PMID- 16107446
TI  - Electronic support for 21st century care.

PMID- 16107447
TI  - Classifying older patients in hospital.

PMID- 16107448
TI  - Vitamin D for older people: how much, for whom and--above all--why?

PMID- 16107449
TI  - The geriatric day hospital.

PMID- 16107450
TI  - What would make a definition of frailty successful?
AB  - At present, frailty is defined variably. Some consensus on a definition is likely
      to emerge, but the basis for a successful definition needs to be explored. Here,
      a classic approach to validation is proposed: a successful definition of frailty
      should be multifactorial but must also manage the many factors in a way that
      takes their interactions into account. It is likely to be correlated with
      disability, co-morbidity and self-rated health, and should identify a group that
      is vulnerable to adverse outcomes. Ideally, it should also be susceptible to
      animal modelling. In that frailty and age are so bound together, it is also
      likely that there will be some age at which virtually all people will be frail,
      by any definition. Apart from being valid, the success of any definition of
      frailty will depend on it being useful to researchers and clinicians. The need
      for progress on our understanding of frailty is evident, but for now, there is
      insufficient evidence to accept a single definition of frailty.

PMID- 16107451
TI  - Good practice in the assessment and management of nocturnal Parkinson's disease
      symptoms.

PMID- 16107452
TI  - Predictors of 1-year mortality in patients discharged from hospital following
      acute exacerbation of chronic obstructive pulmonary disease.
AB  - INTRODUCTION: acute exacerbation of COPD (AECOPD) is a major cause of hospital
      admission, and predicts subsequent medium-term mortality. We aimed to examine
      mortality predictors in patients discharged from hospital after AECOPD. METHODS:
      we obtained baseline demographic and clinical data from 100 patients (mean age
      (range)=73 (60-98) years; 48 males) admitted with AECOPD. All completed the
      following validated questionnaires: a quality of life questionnaire (Breathing
      Problems Questionnaire; BPQ); a screening questionnaire for depression (Brief
      Assessment Schedule Depression Cards; BASDEC); a disability questionnaire
      (Manchester Respiratory Activities of Daily Living questionnaire; MRADL).
      Following discharge all were prospectively followed and survival/mortality at 12
      months confirmed from hospital notes and by contacting general practitioners.
      RESULTS: the prevalence of depression at recruitment was 56%. One-year mortality
      in the whole group was 36%. Odds ratios (95% confidence intervals) for mortality
      predictors (univariate logistic regression analysis) were: use of long-term
      oxygen therapy=2.72 (1.06-6.97); subsequent readmission=2.57 (1.08-6.12); MRADL
      score=0.87 (0.80-0.94) (disability predicting death); BASDEC score=1.13 (1.02
      1.26) (depression predicting death); BPQ score=1.08 (1.04-1.12) (low quality of
      life predicting death); length of original hospital stay=1.03 (1.00-1.07). On
      multivariate logistic regression analysis the only mortality predictor was BPQ
      with an odds ratio (95% confidence limits) of 1.13 (1.04-1.22). In terms of
      mortality prediction for individuals, a threshold MRADL score of <12 gave a
      sensitivity of 86%, specificity of 55%, positive predictive value of 88% and
      negative predictive value of 52%, with similar predictive values using BPQ as an
      independent variable. CONCLUSIONS: 1-year mortality after AECOPD admission is
      high. The presence of depressive illness (which is extremely common), and levels
      of both disability and impairment of quality of life are univariate predictors of
      1-year mortality in this patient group. This model may be useful in predicting
      prognosis for individuals and thus in guiding treatment decisions.

PMID- 16107453
TI  - Electronic tracking of patients with dementia and wandering using mobile phone
      technology.

PMID- 16107454
TI  - NHS Direct and older people.

PMID- 16107455
TI  - Screening for undiagnosed parkinsonism among older people in general practice.

PMID- 16107456
TI  - Diuretic use and bone mineral density in older USA men: the osteoporotic
      fractures in men (MrOS) study.

PMID- 16107457
TI  - Second hip fracture in elderly hip fracture patients: cost and effectiveness of
      fracture prevention treatment.

PMID- 16107458
TI  - Colonoscopy in the very elderly is safe and worthwhile.

PMID- 16107459
TI  - Outcomes of safe, simple colonoscopy in older adults.

PMID- 16107460
TI  - Resident and facility characteristics associated with the site of death among
      Japanese nursing home residents.

PMID- 16107461
TI  - Kyphosis, a rare cause of dysphagia.
AB  - Degenerative kyphosis is mostly asymptomatic. When symptomatic, pain and humping
      of the back are the commonest features. Dysphagia associated with kyphosis is a
      rare presentation, though it is otherwise common in older people due to various
      reasons. We report the case of an 81-year-old kyphotic woman who presented with
      dysphagia. On barium swallow examination, she was found to have an acute bend in
      the mid-oesophagus leading to narrowing, secondary to the kyphosis.

PMID- 16107462
TI  - Non-fatal haemophagocytic syndrome in an elderly patient.
AB  - A frail 78-year-old man presented with lethargy, fever, splenomegaly and
      pancytopenia. Bone marrow aspirate showed marked haemophagocytosis. A diagnosis
      of haemophagocytic syndrome secondary to diffuse splenic large B-cell lymphoma
      was eventually made. Treatment with laparascopic splenectomy was successful.
      Secondary haemophagocytic syndrome is a rare complication of many common
      conditions, and is fatal if untreated. A brief literature review is included.

PMID- 16107463
TI  - Tolterodine-induced hyponatraemia.
AB  - Management of electrolyte abnormalities is challenging in older people as the
      sensation of thirst, renal function and hormonal modulators of the milieu
      interior are often impaired. Furthermore, the complex effects of ageing upon
      these homeostatic mechanisms are often superimposed upon a background of chronic
      disease, malnutrition and co-existent medications. Hyponatraemia is one of the
      commonest electrolyte abnormalities, occurring in approximately 7% of healthy
      elderly persons. Hyponatraemia may only come to light when some other ailment
      prompts investigations or hospital admission. Drug-induced hyponatraemia is
      common in older people and is most commonly associated with diuretics and
      SSRI/SNRI antidepressants, but has also been reported with a wide range of other
      drugs. We believe this is the first case report of hyponatraemia due to
      tolterodine.

PMID- 16107464
TI  - Zopiclone withdrawal: an unusual cause of delirium in the elderly.
AB  - We report a case of an elderly lady who was admitted for congestive heart
      failure. She developed delirium during the course of her hospital stay. Multiple
      investigations were performed but were unremarkable. Finally, a diagnosis of
      abrupt zopiclone withdrawal causing delirium was made. Zopiclone was resumed at a
      lower dose and delirium resolved completely.

PMID- 16107465
TI  - Amoebic liver abscess imitating metastatic caecal carcinoma.
AB  - This case discusses a patient whose initial investigations suggested an incurable
      carcinoma with a poor prognosis, but which later transpired to be an unusual but
      treatable infection.

PMID- 16107466
TI  - Lord Amulree: an appreciation.
AB  - Lord Amulree was unique amongst UK geriatricians in having a 'wide angled' view
      of the care of elderly people. This resulted from his work at the Ministry of
      Health, his clinical commitments and his position in the House of Lords, which
      enabled him to bring the problems of old age, elderly people and infirmity before
      a much wider audience. It can be argued that his joint Parliamentary Presentation
      in 1946 stimulated a surge in publications relating to the care of older people.
      He will be remembered for his maxim 'Adding Life to Years'

PMID- 16107467
TI  - Predictors of delirium during in-hospital rehabilitation in elderly patients
      after hip arthroplasty.

PMID- 16107468
TI  - Re: Prevention of falls--a time to translate evidence into practice.

PMID- 16107470
TI  - Liaison psychiatry for older people--an overlooked opportunity.

PMID- 16107472
TI  - Genetic and epigenetic properties of mouse male germline stem cells during long
      term culture.
AB  - Although stem cells are believed to divide infinitely by self-renewal division,
      there is little evidence that demonstrates their infinite replicative potential.
      Spermatogonial stem cells are the founder cell population for spermatogenesis.
      Recently, in vitro culture of spermatogonial stem cells was described.
      Spermatogonial stem cells can be expanded in vitro in the presence of glial cell
      line-derived neurotrophic factor (GDNF), maintaining the capacity to produce
      spermatogenesis after transplantation into testis. Here, we examined the
      stability and proliferative capacity of spermatogonial stem cells using cultured
      cells. Spermatogonial stem cells were cultured over 2 years and achieved
      approximately 10(85)-fold expansion. Unlike other germline cells that often
      acquire genetic and epigenetic changes in vitro, spermatogonial stem cells
      retained the euploid karyotype and androgenetic imprint during the 2-year
      experimental period, and produced normal spermatogenesis and fertile offspring.
      However, the telomeres in spermatogonial stem cells gradually shortened during
      culture, suggesting that they are not immortal. Nevertheless, the remarkable
      stability and proliferative potential of spermatogonial stem cells suggest that
      they have a unique machinery to prevent transmission of genetic and epigenetic
      damages to the offspring, and these characteristics make them an attractive
      target for germline modification.

PMID- 16107473
TI  - Proximodistal identity during vertebrate limb regeneration is regulated by Meis
      homeodomain proteins.
AB  - The mechanisms by which cells obtain instructions to precisely re-create the
      missing parts of an organ remain an unresolved question in regenerative biology.
      Urodele limb regeneration is a powerful model in which to study these mechanisms.
      Following limb amputation, blastema cells interpret the proximal-most positional
      identity in the stump to reproduce missing parts faithfully. Classical
      experiments showed the ability of retinoic acid (RA) to proximalize blastema
      positional values. Meis homeobox genes are involved in RA-dependent specification
      of proximal cell identity during limb development. To understand the molecular
      basis for specifying proximal positional identities during regeneration, we
      isolated the axolotl Meis homeobox family. Axolotl Meis genes are RA-regulated
      during both regeneration and embryonic limb development. During limb
      regeneration, Meis overexpression relocates distal blastema cells to more
      proximal locations, whereas Meis knockdown inhibits RA proximalization of limb
      blastemas. Meis genes are thus crucial targets of RA proximalizing activity on
      blastema cells.

PMID- 16107474
TI  - Hair follicle renewal: organization of stem cells in the matrix and the role of
      stereotyped lineages and behaviors.
AB  - Hair follicles (HFs) are renewed via multipotent stem cells located in a
      reservoir (the bulge); however, little is known about how they generate multi
      tissue HFs from a proliferative zone (the matrix). To address this issue, we
      temporally induced clonal labeling during HF growth. Challenging the prevailing
      hypothesis, we found that the matrix contains restricted self-renewing stem cells
      for each inner structure. These cells are located around the dermal papilla
      forming a germinative layer. They occupy different proximodistal sectors and
      produce differentiated cells along the matrix radial axis via stereotyped
      lineages and cell behavior. By contrast, the outer layer of HFs displays a mode
      of growth involving apoptosis that coordinates the development of outer and inner
      structures. HF morphology is therefore determined by the organization of cell
      fates along the proximodistal axis and by cell behavior along the radial
      (lateral) axis in the matrix. Thus, our studies suggest that fate and behavior
      are organized by two systems (uncoupled), and this uncoupling may represent a
      fundamental way to simplify morphogenesis.

PMID- 16107475
TI  - Progressive divergence of definitive haematopoietic stem cells from the
      endothelial compartment does not depend on contact with the foetal liver.
AB  - The yolk sac and the para-aortic splanchnopleura/aorta-genital ridges-mesonephros
      (P-Sp/AGM) region are the main sites of haematopoietic activity in the mouse
      embryo at the pre-liver stage of development. By day 11.5 of gestation, the AGM
      region is capable of autonomous initiation and expansion of definitive
      haematopoietic stem cells (HSCs). By day 12.5, HSC activity in the AGM region is
      reduced whilst a second wave of HSCs begins to emerge in the yolk sac. We show
      here that HSCs emerging in both locations are marked by co-expression of the
      endothelial-specific marker VE-cadherin and the pan-leukocyte antigen CD45.
      Phenotypic characterisation using CD31, TIE2, FLK1, Ac-LDL receptors, and CD34
      markers demonstrated significant similarities between this VE-cadherin+CD45+
      ;double-positive' population and endothelial cells suggesting a common origin for
      these cells. The double-positive fraction also expressed the stem cell markers
      Kit, Sca1 and AA4.1. Long-term transplantation experiments demonstrated that the
      double-positive population, which constituted less than 0.05% of the day 11.5 AGM
      region and the day 12.5 yolk sac, is highly enriched for HSCs. In vitro assays
      showed that this population is also enriched for myeloid progenitors. During
      foetal liver colonization, circulating HSCs remained within the VE-cadherin+ cell
      fraction, although their phenotypic similarity with endothelial cells became less
      prominent. Upon liver colonisation the majority of HSCs downregulated VE
      cadherin, expression of which was completely lost in the adult bone marrow.
      Partial loss of VE-cadherin expression in HSCs can be observed extra hepatically
      in the advanced AGM region by E12.5. Similarly, the CD34+KIT+ population in the
      placenta, recently identified as a reservoir of HSCs, partly lose VE-cadherin
      expression by E12.5. By culturing isolated E11.5 AGM region and E12.5 yolk sac we
      show that the developmental switch from a ;primary' VE-cadherin+CD45+ to a more
      ;advanced' VE-cadherin-CD45+ phenotype does not require contact of HSCs with the
      liver and is probably a function of developmental time.

PMID- 16107476
TI  - EPHB4 regulates chemokine-evoked trophoblast responses: a mechanism for
      incorporating the human placenta into the maternal circulation.
AB  - In humans, fetal cytotrophoblasts leave the placenta and enter the uterine wall,
      where they preferentially remodel arterioles. The fundamental mechanisms that
      govern these processes are largely unknown. Previously, we have shown that
      invasive cytotrophoblasts express several chemokines, as well as the receptors
      with which they interact. Here, we report that these ligand-receptor interactions
      stimulate cytotrophoblast migration to approximately the same level as a growth
      factor cocktail that includes serum. Additionally, cytotrophoblast commitment to
      uterine invasion was accompanied by rapid downregulation of EPHB4, a
      transmembrane receptor associated with venous identity, and upregulation of
      ephrin B1. Within the uterine wall, the cells also upregulated expression of
      ephrin B2, an EPH transmembrane ligand that is associated with arterial identity.
      In vitro cytotrophoblasts avoided EPHB4-coated substrates; upon co-culture with
      3T3 cells expressing this molecule, their migration was significantly inhibited.
      As to the mechanisms involved, cytotrophoblast interactions with EPHB4
      downregulated chemokine-induced but not growth factor-stimulated migration. We
      propose that EPHB4/ephrin B1 interactions generate repulsive signals that direct
      cytotrophoblast invasion toward the uterus, where chemokines stimulate
      cytotrophoblast migration through the decidua. When cytotrophoblasts encounter
      EPHB4 expressed by venous endothelium, ephrin B-generated repulsive signals and a
      reduction in chemokine-mediated responses limit their interaction with veins.
      When they encounter ephrin B2 ligands expressed in uterine arterioles, migration
      is permitted. The net effect is preferential cytotrophoblast remodeling of
      arterioles, a hallmark of human placentation.

PMID- 16107477
TI  - Genetic and cellular analyses of zebrafish atrioventricular cushion and valve
      development.
AB  - Defects in cardiac valve morphogenesis and septation of the heart chambers
      constitute some of the most common human congenital abnormalities. Some of these
      defects originate from errors in atrioventricular (AV) endocardial cushion
      development. Although this process is being extensively studied in mouse and
      chick, the zebrafish system presents several advantages over these models,
      including the ability to carry out forward genetic screens and study vertebrate
      gene function at the single cell level. In this paper, we analyze the cellular
      and subcellular architecture of the zebrafish heart during stages of AV cushion
      and valve development and gain an unprecedented level of resolution into this
      process. We find that endocardial cells in the AV canal differentiate
      morphologically before the onset of epithelial to mesenchymal transformation,
      thereby defining a previously unappreciated step during AV valve formation. We
      use a combination of novel transgenic lines and fluorescent immunohistochemistry
      to analyze further the role of various genetic (Notch and Calcineurin signaling)
      and epigenetic (heart function) pathways in this process. In addition, from a
      large-scale forward genetic screen we identified 55 mutants, defining 48
      different genes, that exhibit defects in discrete stages of AV cushion
      development. This collection of mutants provides a unique set of tools to further
      our understanding of the genetic basis of cell behavior and differentiation
      during AV valve development.

PMID- 16107478
TI  - The gene ENHANCER OF PINOID controls cotyledon development in the Arabidopsis
      embryo.
AB  - During Arabidopsis embryo development, cotyledon primordia are generated at
      transition stage from precursor cells that are not derived from the embryonic
      shoot apical meristem (SAM). To date, it is not known which genes specifically
      instruct these precursor cells to elaborate cotyledons, nor is the role of auxin
      in cotyledon development clear. In laterne mutants, the cotyledons are precisely
      deleted, yet the hypocotyl and root are unaffected. The laterne phenotype is
      caused by a combination of two mutations: one in the PINOID (PID) gene and
      another mutation in a novel locus designated ENHANCER OF PINOID (ENP). The
      expression domains of shoot apex organising genes such as SHOOT MERISTEMLESS
      (STM) extend along the entire apical region of laterne embryos. However, analysis
      of pid enp stm triple mutants shows that ectopic activity of STM does not appear
      to cause cotyledon obliteration. This is exclusively caused by enp in concert
      with pid. In pinoid embryos, reversal of polarity of the PIN1 auxin transport
      facilitator in the apex is only occasional, explaining irregular auxin maxima in
      the cotyledon tips. By contrast, polarity of PIN1:GFP is completely reversed to
      basal position in the epidermal layer of the laterne embryo. Consequently auxin,
      which is believed to be essential for organ formation, fails to accumulate in the
      apex. This strongly suggests that ENP specifically regulates cotyledon
      development through control of PIN1 polarity in concert with PID.

PMID- 16107479
TI  - The HMX homeodomain protein MLS-2 regulates cleavage orientation, cell
      proliferation and cell fate specification in the C. elegans postembryonic
      mesoderm.
AB  - The proper formation of a complex multicellular organism requires the precise
      coordination of many cellular events, including cell proliferation, cell fate
      specification and differentiation. The C. elegans postembryonic mesodermal
      lineage, the M lineage, allows us to study mechanisms coordinating these events
      at single cell resolution. We have identified an HMX homeodomain protein MLS-2 in
      a screen for factors required for M lineage patterning. The MLS-2 protein is
      present in nuclei of undifferentiated cells in the early M lineage and in a
      subset of head neurons. In the M lineage, MLS-2 activity appears to be tightly
      regulated at the fourth round of cell division, coincident with the transition
      from proliferation to differentiation. A predicted null allele of mls-2, cc615,
      causes reduced cell proliferation in the M lineage, whereas a semi-dominant, gain
      of-function allele, tm252, results in increased cell proliferation. Loss or
      overexpression of mls-2 also affects cleavage orientation and cell fate
      specification in the M lineage. We show that the increased cell proliferation in
      mls-2(tm252) mutants requires CYE-1, a G1 cell cycle regulator. Furthermore, the
      C. elegans Myod homolog HLH-1 acts downstream of mls-2 to specify M-derived
      coelomocyte cell fates. Thus MLS-2 functions in a cell type-specific manner to
      regulate both cell proliferation and cell fate specification.

PMID- 16107480
TI  - Drosophila Myt1 is a Cdk1 inhibitory kinase that regulates multiple aspects of
      cell cycle behavior during gametogenesis.
AB  - The metazoan Wee1-like kinases Wee1 and Myt1 regulate the essential mitotic
      regulator Cdk1 by inhibitory phosphorylation. This regulatory mechanism, which
      prevents Cdk1 from triggering premature mitotic events, is also induced during
      the DNA damage response and used to coordinate cell proliferation with crucial
      developmental events. Despite the previously demonstrated role for Myt1
      regulation of Cdk1 during meiosis, relatively little is known of how Myt1
      functions at other developmental stages. To address this issue, we have
      undertaken a functional analysis of Drosophila Myt1 that has revealed novel
      developmental roles for this conserved cell cycle regulator during gametogenesis.
      Notably, more proliferating cells were observed in myt1 mutant testes and ovaries
      than controls. This can partly be attributed to ectopic division of germline
      associated somatic cells in myt1 mutants, suggesting that Myt1 serves a role in
      regulating exit from the cell cycle. Moreover, mitotic index measurements
      suggested that germline stem cells proliferate more rapidly, in myt1 mutant
      females. In addition, male myt1 germline cells occasionally undergo an extra
      mitotic division, resulting in meiotic cysts with twice the normal numbers of
      cells. Based on these observations, we propose that Myt1 serves unique Cdk1
      regulatory functions required for efficient coupling of cell differentiation with
      cell cycle progression.

PMID- 16107481
TI  - Auxin response factors ARF6 and ARF8 promote jasmonic acid production and flower
      maturation.
AB  - Pollination in flowering plants requires that anthers release pollen when the
      gynoecium is competent to support fertilization. We show that in Arabidopsis
      thaliana, two paralogous auxin response transcription factors, ARF6 and ARF8,
      regulate both stamen and gynoecium maturation. arf6 arf8 double-null mutant
      flowers arrested as infertile closed buds with short petals, short stamen
      filaments, undehisced anthers that did not release pollen and immature gynoecia.
      Numerous developmentally regulated genes failed to be induced. ARF6 and ARF8 thus
      coordinate the transition from immature to mature fertile flowers. Jasmonic acid
      (JA) measurements and JA feeding experiments showed that decreased jasmonate
      production caused the block in pollen release, but not the gynoecium arrest. The
      double mutant had altered auxin responsive gene expression. However, whole flower
      auxin levels did not change during flower maturation, suggesting that auxin might
      regulate flower maturation only under specific environmental conditions, or in
      localized organs or tissues of flowers. arf6 and arf8 single mutants and
      sesquimutants (homozygous for one mutation and heterozygous for the other) had
      delayed stamen development and decreased fecundity, indicating that ARF6 and ARF8
      gene dosage affects timing of flower maturation quantitatively.

PMID- 16107483
TI  - Social capital and the history of mortality in Britain.

PMID- 16107484
TI  - The clinical role of 'non-invasive' coronary angiography by multidetector spiral
      computed tomography: yet to be defined.

PMID- 16107485
TI  - Mortality at 1 year for the direct comparison of tirofiban and abciximab during
      percutaneous coronary revascularization: do tirofiban and ReoPro give similar
      efficacy outcomes at trial 1-year follow-up.
AB  - AIMS: Compared with placebo, abciximab has been associated with mortality
      reduction at late follow-up. The TARGET trial was performed to test whether
      tirofiban and abciximab provide similar efficacy outcomes among patients
      undergoing non-emergent, stent-based percutaneous coronary intervention. We
      report here the 1-year mortality of the study population. METHODS AND RESULTS: In
      18 countries at 149 hospitals, 4,809 patients undergoing elective or urgent stent
      implantation were randomly assigned a bolus and infusion of tirofiban or
      abciximab. Ischaemic events were assessed at 30 days and 6 months and mortality
      was assessed at 1 year. We previously reported that abciximab was superior to
      tirofiban considering the composite rate of death or myocardial infarction at 30
      days among all patients and at 6 months among those with an acute coronary
      syndrome (ACS). At 1-year follow-up death occurred in 46 (1.9%) patients who
      received tirofiban and 42 (1.7%) patients who received abciximab (hazard ratio
      1.10, 95% CI 0.72-1.67; P=0.660). Mortality rates for patients with ACS were 2.3%
      with tirofiban vs. 2.2% with abciximab (hazard ratio 1.03, 95% CI 0.64-1.67;
      P=0.897) and those without ACS were 1.4 vs. 1.0% (hazard ratio 1.32, 95% CI 0.56
      3.13; P=0.530). CONCLUSION: At 1 year, tirofiban provided a similar level of
      survival benefit compared with abciximab.

PMID- 16107486
TI  - Cardiac complications relating to pregnancy and recurrence of disease in the
      offspring of women with atrioventricular septal defects.
AB  - AIMS: In most pregnancy reports, atrioventricular septal defects (AVSD) are not
      differentiated from more simple septal defects, thus underestimating the risks of
      pregnancy. To investigate the magnitude and determinants of risk during pregnancy
      in female patients with balanced AVSD. METHODS AND RESULTS: Using a nation-wide
      registry (CONCOR), 79 female patients with balanced/isolated AVSD were
      identified. A total of 29 patients had 62 pregnancies, including 12 miscarriages
      (19%) and two elective abortions. Detailed recordings of each completed (>20
      weeks gestation) pregnancy (n=48, 26 women) were obtained. Cardiovascular events
      complicated almost 40% of the completed pregnancies. In particular, post-partum
      persistence of pregnancy-related New York Heart Association (NYHA) class
      deterioration [23% mainly patients with residual atrial septal defects (ASD)] and
      deterioration of pre-existing left AV-valvular regurgitation (17%) were
      frequently recorded. Additional cardiac complications were arrhythmias (19%) and
      symptomatic heart failure (2%). Congenital heart disease (CHD) recurred in six
      children (12%): AVSD (n=4, three with left-sided hypoplasia), patent ductus
      arteriosus (n=1), and ASD (n=1). Three children died including two children with
      left-sided hypoplasia. CONCLUSION: Pregnancy is not always well tolerated in
      women with AVSD, predominantly due to NYHA class deterioration and worsening of
      pre-existing AV-valvular regurgitation. Offspring mortality is high (6.3%),
      primarily due to recurrence of complex CHD.

PMID- 16107487
TI  - Novel mutations in three families confirm a major role of COL4A1 in hereditary
      porencephaly.
AB  - BACKGROUND: Porencephaly (cystic cavities of the brain) is caused by perinatal
      vascular accidents from various causes. Several familial cases have been
      described and autosomal dominant inheritance linked to chromosome 13q has been
      suggested. COL4A1 is an essential component in basal membrane stability. Mouse
      mutants bearing an in-frame deletion of exon 40 of Col4a1 either die from
      haemorrhage in the perinatal period or have porencephaly in survivors. A report
      of inherited mutations in COL4A1 in two families has shown that familial
      porencephaly may have the same cause in humans. OBJECTIVE: To describe three
      novel COL4A1 mutations. RESULTS: The three mutations occurred in three unrelated
      Dutch families. There were two missense mutations of glycine residues predicted
      to result in abnormal collagen IV assembly, and one mutation predicted to abolish
      the traditional COL4A1 start codon. The last mutation was also present in an
      asymptomatic obligate carrier with white matter abnormalities on brain magnetic
      resonance imaging. CONCLUSIONS: This observation confirms COL4A1 as a major locus
      for genetic predisposition to perinatal cerebral haemorrhage and porencephaly and
      suggests variable expression of COL4A1 mutations.

PMID- 16107488
TI  - Ambivalence and uncertainty: experiences of and attitudes towards addiction and
      smoking cessation in the mid-to-late teens.
AB  - The late teens is an important transitional period as adolescents move into new
      social worlds which support or challenge their smoking. This paper draws on
      research with 99 Scottish 16- to 19-year olds which explored their understanding
      of their smoking and attitudes towards quitting and cessation support. The study
      involved qualitative interviews mostly with friendship pairs. Interviewees also
      completed a brief smoking questionnaire. Most regarded themselves as smokers but
      few thought they were addicted. Many were interested in quitting but this was not
      a priority. Perceived barriers to quitting related primarily to habitual and
      social aspects of dependence including friends' smoking, the smoking culture at
      work or college, stress and boredom. Few were interested in nicotine replacement
      therapy or cessation services, which they felt belonged to the world of older
      addicted smokers. The most effective quitting strategy was thought to be will
      power. Traditional cessation services are therefore in their current form
      unlikely to appeal to older adolescents. Services aimed at this age group need to
      be grounded in their understandings of smoking and the social factors which
      support smoking. Young smokers should also be helped to understand how support
      may increase quitting success and how encourage quitting before smoking becomes
      entrenched in their daily routines.

PMID- 16107489
TI  - Unquoted, unchallenged, general practice research will be casting pearls before
      swine.

PMID- 16107490
TI  - Long-term prognosis of acute otitis media in infancy: determinants of recurrent
      acute otitis media and persistent middle ear effusion.
AB  - OBJECTIVES: Children under 2 years of age with acute otitis media are known to
      have a relatively poor prognosis. The objective of this study was to assess
      whether known determinants for recurrent acute otitis media and persistent middle
      ear effusion after an episode of acute otitis media during childhood also apply
      to children under 2 years. METHODS:  STUDY DESIGN: prospective study of 210
      children under 2, with identification of potential prognostic determinants.
      Univariate and multivariate logistic regression analyses were applied to evaluate
      which parameters independently contributed to the prediction of both outcome
      measures (recurrent acute otitis media and persistent middle ear effusion). A
      prognostic function was developed, and the area under the receiving operating
      characteristic (ROC) was used to estimate the predictive ability of the
      prognostic models. POPULATION: children under 2 years of age with an episode of
      acute otitis media in family practice. OUTCOMES MEASURED: recurrent acute otitis
      media and persistent middle ear effusion. RESULTS: For the outcome recurrent
      acute otitis media data from 210 children were used and winter season, male sex,
      passive smoking and persistent symptoms for more than 10 days at presentation
      were independent prognostic determinants. For the outcome persistent middle ear
      effusion data from 190 children were used and winter season, bilateral disease at
      entry, a sibling history of recurrent acute otitis media, and a previous episode
      of acute otitis media independently predicted the outcome. No sufficiently
      discriminatory prognostic model could be constructed for either outcome measure.
      CONCLUSION: Prediction of recurrent acute otitis media or persistent middle ear
      effusion in individual young children remains poor.

PMID- 16107491
TI  - What effects do patients feel from their antihypertensive tablets and how do they
      react to them? Qualitative analysis of interviews with patients.
AB  - BACKGROUND: Patients commonly experience palpable effects from antihypertensives.
      Few studies have examined patients' experiences of these effects and how they
      influence patients' behaviour and medicine-taking. OBJECTIVES: To describe the
      palpable effects that patients attribute to their antihypertensive tablets and
      the ways that they react to them. METHODS: In depth interviews with a maximum
      variety sample of 38 patients taking antihypertensive medication in 2 mainly
      urban UK general practices. Qualitative analysis based upon the study's
      objectives. RESULTS: Most patients attributed palpable effects to their
      antihypertensives. Some effects were welcome, attributed to lowered blood
      pressure or a calming effect of tablets, but others were unwelcome. As a result
      of these, some patients stopped their tablets, but more continued taking tablets
      as usual, took their tablets in a different way, or countered unwelcome effects
      by some other means. Although patients discussed stopping tablets with their
      doctor, they commonly did not discuss other reactions. Patients who accepted
      persistent unwelcome effects balanced them against reasons to take medication:
      positive experiences with doctors; perceived benefits of medication; or pragmatic
      considerations. These reasons overlap with those described previously as
      balancing patients' reservations about medicines. CONCLUSION: The term 'side
      effect' fails to distinguish between palpable effects that are welcome or
      unwelcome, or to recognise that some unwelcome effects may nevertheless be
      acceptable. If clinicians explore the range of palpable effects that patients
      attribute to antihypertensives and patients' possible preparedness to tolerate
      unwelcome effects, they will be better able to identify patients' preferences in
      this area.

PMID- 16107492
TI  - Is a computer questionnaire of childhood asthma acceptable in general practice?
AB  - OBJECTIVES: To determine whether a previously-validated touch screen computer
      program of symptoms and management of childhood asthma is acceptable to parents
      who accompany their children to consult a GP, and to examine whether any parent
      characteristics are associated with acceptability. METHODS: Conducted in general
      practice in Newcastle, NSW, Australia. A cross sectional pen and paper survey was
      given to parents of children consulting a GP after completing the computer
      questionnaire on childhood asthma in the waiting room. Measurements were
      frequencies of Likert scale responses to statements concerning the computer
      questionnaire, compared with demographic and personal characteristics. RESULTS:
      High levels of acceptability of the asthma computer questionnaire were reported
      by the 198 respondents, with most being willing to do the same program once or
      twice a year (87%), or to do similar programs on other topics (91%). Most
      respondents (81%) agreed that the computer program was enjoyable, and very few
      (8%) would have preferred to answer the asthma questions by pen and paper rather
      than by computer. Two or more children accompanying the parent was the
      characteristic most associated with less positive responses. CONCLUSIONS: Overall
      the high acceptability of this questionnaire suggests that this computerised
      format is an appropriate method of screening children for asthma and determining
      their current management. As a large component of underdiagnosis of asthma is
      lack of reporting to the doctor, this valid and acceptable diagnostic aid has the
      potential to improve detection of unreported asthma, and also to identify high
      risk individuals.

PMID- 16107493
TI  - Making sense of aches and pains.
AB  - BACKGROUND: The uncertainty about the status of upper limb disorders (ULDs),
      particularly the non-specific conditions, is believed to have consequences for
      clinical management and patient care. OBJECTIVE: This paper presents evidence
      about how sufferers with ULDs respond to their pain, how their pain is managed,
      when and who they go to for formal help and how sufferers evaluate the care they
      receive. METHODS: The data analysis is derived from face-to-face, informal
      interviews with sufferers with a broad spectrum of upper limb disorders (n = 47).
      These informants were selected according to strict criteria from a 'screening'
      postal survey of the working population (25-64 years) in south-west England (n =
      2781). RESULTS: Ideas about causation were crucial to understanding patterns of
      illness action and help seeking behaviour. The common strategy was to wait and
      see what happens as the pain was believed to be a natural part of the ageing
      process. Explanations invoking psychosocial and work related causes were less
      common and tended to be used when biomechanical explanations were no longer
      appropriate. Self-management was the preferred strategy but orthodox
      practitioners were usually the first choice for formal care. Complementary and
      alternative medicines (CAM) were popular but were used to complement orthodox
      care. Practitioners were evaluated mainly in terms of their ability to alleviate
      pain. CONCLUSION: There is a need for orthodox and non-orthodox care to be
      closely integrated in primary care and GPs should not depend on orthodox
      medications alone when caring for patients with upper limb pain.

PMID- 16107494
TI  - The use of medication for chronic pain in primary care, and the potential for
      intervention by a practice-based pharmacist.
AB  - BACKGROUND AND OBJECTIVES: The majority of people with chronic pain use
      analgesics regularly. Ensuring their safe and appropriate use is important. This
      study aimed to describe patterns of analgesic prescribing in one general
      practice, devise a method of identifying chronic pain patients from prescribing
      records, and assess prescribing recommendations made after a pharmacist-led
      review of analgesic prescribing and identify the proportion of these acted on by
      GPs. METHODS: Prescribing records in a practice of 6720 patients were searched
      and 678 patients were identified as receiving prescriptions for analgesics. 230
      were invited to participate and sent a questionnaire, including questions about
      chronic pain severity, general health and medications used. This was repeated
      after six months. The pharmacist completed a detailed medication review using
      information from medical records, questionnaires and personal interviews.
      Prescribing recommendations were made to GPs. RESULTS: 192 recommendations about
      safe or appropriate prescribing were made for 86% of participants after records
      review, 56% being directly related to analgesic use. After 6 months all
      recommendations had been implemented in 77% of the patients. Few additional
      recommendations were made after interview. There was little or no relationship
      with changes in chronic pain severity or general or psychological health.
      CONCLUSIONS: We have demonstrated a method of identifying patients with chronic
      pain in primary care, and the feasibility and acceptability of a pharmacist-led
      intervention. This is of potential value in primary care, as relevant prescribing
      recommendations were made for most patients although further research is required
      to assess these.

PMID- 16107495
TI  - Predictors of discontinuation of benzodiazepine prescription after sending a
      letter to long-term benzodiazepine users in family practice.
AB  - BACKGROUND: Predictors of benzodiazepine discontinuation after sending a
      discontinuation letter by the family practitioner have not been established
      sufficiently. OBJECTIVE: To identify predictors of short- and long-term
      discontinuation of benzodiazepine use and relapse in use after a minimal
      intervention with a discontinuation letter followed by an offer for an evaluation
      consultation. METHODS: Predictors of benzodiazepine discontinuation and relapse
      in use were studied by logistic regression analysis and survival analysis within
      a family practice population of long-term benzodiazepine users (n = 1707)
      addressed by a discontinuation letter and followed for 21 months. RESULTS: A
      lower baseline prescription, a shorter duration of use, male gender and use of an
      agent with a half-life time <24 hours were predictive of complete discontinuation
      in the short (6 months) and long term (21 months). Multiple agent use at
      baseline, use of antidepressants at 6 months and benzodiazepine type
      (anxiolytic/hypnotic) at baseline predicted relapse. Attendance at an evaluation
      consultation 3 months after the letter was sent was not predictive of
      discontinuation or relapse. CONCLUSIONS: Amount of baseline use and duration of
      use are the main determinative characteristics of successful discontinuation. The
      discontinuation letter intervention is suitable for use with a broad group of
      long-term benzodiazepine users in family practice and can be used as a first step
      within a stepped care approach to decrease long-term benzodiazepine use.

PMID- 16107496
TI  - Gefitinib (ZD1839) combined with weekly epirubicin in patients with metastatic
      breast cancer: a phase I study with biological correlate.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) is overexpressed in
      approximately 50% of invasive breast carcinomas and it is correlated with hormone
      resistance and poor prognosis. EGFR suppression by gefitinib, a quinazoline
      derivative that inhibits phosphorylation of the specific receptor, represents a
      novel therapeutic strategy. A dose-finding study was performed to evaluate the
      combination of gefitinib with weekly epirubicin in patients with pretreated
      metastatic breast cancer. METHODS: Fifteen patients were enrolled at four
      sequential dose levels. Gefitinib was administered orally, at the fixed daily
      dose of 250 mg. The starting dose of epirubicin was 20 mg/m2. Escalating dose
      levels of epirubicin were planned by increments of 5 mg/m2 per level, up to the
      maximum tolerated dose (MTD). Pharmacodynamic studies were performed by
      determining serum and tissue ERBB2 and EGFR. RESULTS: At the first three dose
      levels tested no patient experienced a dose-limiting toxicity (DLT). In cohort 4,
      two patients experienced DLTs (grade 4 dyspnea and asthenia, grade 3 diarrhea and
      thrombocytopenia) identifying the MTD of epirubicin as 35 mg/m2. Of the 14 cases
      assessable for response, partial response was documented in two patients, and
      stable disease in seven, giving an overall disease control rate of 64.2%. The
      comparison of pre- and post-therapy ERBB2 and EGFR values was not statistically
      significant between the subgroups of patients regarding responsiveness to
      treatment. CONCLUSIONS: The recommended dose of epirubicin for phase II studies
      is 30 mg/m2 in combination with gefitinib at the daily dose of 250 mg.
      Pharmacodynamic studies did not identify any biomarker predictive of response.

PMID- 16107497
TI  - Molecular staging of the sentinel lymph node in melanoma patients: correlation
      with clinical outcome.
AB  - BACKGROUND: This study was designed to determine the debated prognostic
      significance of reverse transcriptase-polymerase chain reaction (RT-PCR)
      positivity in melanoma patients' sentinel lymph node (SLN) negative by
      conventional histopathology (PATH). PATIENTS AND METHODS: Patients with primary
      stage I-II cutaneous melanoma underwent radioguided sentinel lymphadenectomy.
      Their SLNs were assessed for tyrosinase (Tyr) and melanoma antigens recognized by
      T-cells (MART-1) mRNA expression using RT-PCR, in parallel with hematoxylin and
      eosin staining and immunohistochemistry. Tyr and MART-1 expression in the SLNs
      were correlated with PATH assay results, standard prognostic factors, time to
      progression and overall survival. RESULTS: Twenty-three of the 124 patients
      (18.5%) had positive SLNs by both PATH and RT-PCR (PATH+/PCR+). Sixteen patients
      (13%) were negative by PATH and positive by RT-PCR (PATH-/PCR+). Eighty-five
      patients (68.5%) had SLNs that were negative by both PATH and RT-PCR (PATH-/PCR
      ). At a median follow-up of 30 months, recurrence rates among the three cohorts
      were statistically different (PATH+/PCR+, 60%; PATH-/PCR+, 31%; PATH-/PCR-,
      9.4%). Seven of 23 (30%) and two of 16 (12.5%) patients died in the PATH+/PCR+
      and PATH-/PCR+ SLN groups, respectively, whereas no patient died in the PATH-/PCR
      SLN group. CONCLUSIONS: RT-PCR is more sensitive than PATH to detect SLN
      metastases and it is a reliable predictor of disease relapse in stage I-II
      melanoma patients.

PMID- 16107498
TI  - Activating E2Fs mediate transcriptional regulation of human E2F6 repressor.
AB  - E2F6 is believed to repress E2F-responsive genes and therefore serve a role in
      cell cycle regulation. Analysis of the human E2F6 promoter region revealed the
      presence of two putative E2F binding sites, both of which were found to be
      functionally critical because deletion or mutations of these sites abolished
      promoter activity. Ectopic expression of E2F1 protein was found to increase E2F6
      mRNA levels and significantly upregulate E2F6 promoter activity. Deletion or
      mutation of the putative E2F binding sites nullified the effects of E2F1 on the
      E2F6 promoter activity. Studies on the temporal induction of E2F family members
      demonstrated that the activating E2Fs, and most notably E2F1, were upregulated
      before E2F6 during cell cycle progression at the G1/S phase, and this coincided
      with the time course of induction experienced by the E2F6 promoter during the
      course of the cell cycle. EMSAs indicated the specific binding of nuclear
      complexes to the E2F6 promoter that contained E2F1-related species whose binding
      was specifically competed by the consensus E2F binding site. Chromatin
      immunoprecipitation assays with anti-E2Fs demonstrated the association of E2F
      family members with the E2F6 promoter in vivo. These data indicate that the
      expression of the E2F6 repressor is influenced at the transcriptional level by
      E2F family members and suggest that interplay among these transcriptional
      regulators, especially E2F1, may be critical for cell cycle regulation.

PMID- 16107499
TI  - Augmented extracellular ATP signaling in bladder urothelial cells from patients
      with interstitial cystitis.
AB  - Interstitial cystitis (IC) is an idiopathic hypersensory condition of the bladder
      associated with increased urinary ATP and increased stretch-activated ATP release
      by bladder urothelial cells (BUCs), suggesting augmented purinergic signaling in
      the bladder. To test this theory further, monolayers of cultured BUCs derived
      from bladder biopsies obtained from patients with IC and control patients were
      stimulated with 10-30 microM ATP with subsequent measurement of extracellular ATP
      levels using the luciferin-luciferase assay. Stimulation with 30 microM ATP
      resulted in IC supernatant containing several-fold more ATP than control BUCs
      initially, followed by a slower decrease in ATP levels. This difference in ATP
      levels was not completely due to activity of cellular ecto-ATPase, because
      blockade with ARL67156 did not normalize the difference. Exposure to hypotonic
      solutions resulted in similar extracellular ATP concentrations in IC and control
      BUCs, but there was a slower decrease in ATP levels in IC supernatants. Treatment
      of IC BUCs with 10-40 microM suramin, a nonspecific P2 receptor antagonist,
      significantly attenuated the IC BUC response to extracellular ATP, restoring IC
      BUCs to a control phenotype. Pretreatment of IC BUCs with 20 ng/ml of heparin
      binding EGF-like growth factor (HB-EGF), which previously has been shown to be
      decreased in IC urine specimens, also restored IC BUCs to a control phenotype
      with respect to response to ATP stimulation. In conclusion, IC BUCs have
      augmented extracellular ATP signaling that could be blocked by suramin and HB
      EGF. These findings suggest the possible development of future novel therapeutic
      techniques.

PMID- 16107500
TI  - Cytosolic COOH terminus of the peptide transporter PEPT2 is involved in apical
      membrane localization of the protein.
AB  - The peptide transporter PEPT2 is a polytopic transmembrane protein that mediates
      the cellular uptake of di- and tripeptides and a variety of peptidomimetics. It
      is widely expressed in mammalian tissues, including kidney, lung, mammary gland,
      choroid plexus, and glia cells. In renal tubular cells, PEPT2 is exclusively
      found at the apical membrane. The molecular mechanisms underlying this polarized
      expression and targeting to the brush-border membrane are not known. We have
      explored the role of the 36 COOH-terminal amino acid residues in PEPT2
      trafficking and apical expression. EGFP-tagged PEPT2 wild-type transporter and
      various truncated and mutant proteins were expressed in the polarized proximal
      tubule cell lines SKPT and OK, and the cellular distribution of the fusion
      proteins was assessed using confocal microscopy. Whereas deletion of the last
      seven amino acids (delC7) did not alter PEPT2 surface expression, deletion of the
      next residue (delC8) or up to 30 terminal amino acids resulted in impaired apical
      expression and distinct accumulation of mutant proteins in endosomal and
      lysosomal vesicles. Truncation of more amino acids (delC36) containing tyrosine
      based motifs led to a rather diffuse intracellular distribution pattern.
      Mutations introduced at isoleucine-720 (I720A) and leucine-722 (I722A) also
      caused an impaired surface appearance. Internalization assays revealed a higher
      endocytotic rate of the PEPT2 mutants I720A, L722A, and delC36. Our data suggest
      that a three-amino acid stretch (INL) and tyrosine-based motifs within the COOH
      tail of PEPT2 are involved in PEPT2's apical membrane localization and membrane
      steady-state level.

PMID- 16107501
TI  - Activation of large-conductance, Ca2+-activated K+ channels by cannabinoids.
AB  - We have examined the effects of the cannabinoid anandamide (AEA) and its stable
      analog, methanandamide (methAEA), on large-conductance, Ca2+-activated K+ (BK)
      channels using human embryonic kidney (HEK)-293 cells, in which the alpha-subunit
      of the BK channel (BK-alpha), both alpha- and beta1-subunits (BK-alphabeta1), or
      both alpha- and beta4-subunits (BK-alphabeta4) were heterologously expressed. In
      a whole cell voltage-clamp configuration, each cannabinoid activated BK
      alphabeta1 within a similar concentration range. Because methAEA could potentiate
      BK-alpha, BK-alphabeta1, and BK-alphabeta4 with similar efficacy, the beta
      subunits may not be involved at the site of action for cannabinoids. Under cell
      attached patch-clamp conditions, application of methAEA to the bathing solution
      increased BK channel activity; however, methAEA did not alter channel activity in
      the excised inside-out patch mode even when ATP was present on the cytoplasmic
      side of the membrane. Application of methAEA to HEK-BK-alpha and HEK-BK
      alphabeta1 did not change intracellular Ca2+ concentration. Moreover, methAEA
      induced potentiation of BK channel currents was not affected by pretreatment with
      a CB1 antagonist (AM251), modulators of G proteins (cholera and pertussis toxins)
      or by application of a selective CB2 agonist (JWH133). Inhibitors of CaM, PKG,
      and MAPKs (W7, KT5823, and PD-98059) did not affect the potentiation. Application
      of methAEA to mouse aortic myocytes significantly increased BK channel currents.
      This study provides the first direct evidence that unknown factors in the
      cytoplasm mediate the ability of endogenous cannabinoids to activate BK channel
      currents. Cannabinoids may be hyperpolarizing factors in cells, such as arterial
      myocytes, in which BK channels are highly expressed.

PMID- 16107502
TI  - Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal
      collecting duct cells.
AB  - Aldosterone classically modulates Na transport in tight epithelia such as the
      renal collecting duct (CD) through the transcellular route, but it is not known
      whether the hormone could also affect paracellular permeability. Such
      permeability is controlled by tight junctions (TJ) that form a size- and charge
      selective barrier. Among TJ proteins, claudin-4 has been highlighted as a key
      element to control paracellular charge selectivity. In RCCD2 CD cells grown on
      filters, we have identified novel early aldosterone effects on TJ. Endogenous
      claudin-4 abundance and cellular localization were unaltered by aldosterone.
      However, the hormone promoted rapid (within 15-20 min) and transient
      phosphorylation of endogenous claudin-4 on threonine residues, without affecting
      tyrosine or serine; this event was fully developed at 10 nM aldosterone and
      appeared specific for aldosterone (because it is not observed after dexamethasone
      treatment and it depends on mineralocorticoid receptor occupancy). Within the
      same delay, aldosterone also promoted an increased apical-to-basal passage of
      125I (a substitute for 36Cl), whereas 22Na passage was unaffected; paracellular
      permeability to [3H]mannitol was also reduced. Later on (45 min), a fall in
      transepithelial resistance was observed. These data indicate that aldosterone
      modulates TJ properties in renal epithelial cells.

PMID- 16107503
TI  - mu-Calpain and calpain-3 are not autolyzed with exhaustive exercise in humans.
AB  - mu-Calpain and calpain-3 are Ca2+-dependent proteases found in skeletal muscle.
      Autolysis of calpains is observed using Western blot analysis as the cleaving of
      the full-length proteins to shorter products. Biochemical assays suggest that mu
      calpain becomes proteolytically active in the presence of 2-200 microM Ca2+.
      Although calpain-3 is poorly understood, autolysis is thought to result in its
      activation, which is widely thought to occur at lower intracellular Ca2+
      concentration levels ([Ca2+]i; approximately 1 microM) than the levels at which
      mu-calpain activation occurs. We have demonstrated the Ca2+-dependent autolysis
      of the calpains in human muscle samples and rat extensor digitorum longus (EDL)
      muscles homogenized in solutions mimicking the intracellular environment at
      various [Ca2+] levels (0, 2.5, 10, and 25 microM). Autolysis of calpain-3 was
      found to occur across a [Ca2+] range similar to that for mu-calpain, and both
      calpains displayed a seemingly higher Ca2+ sensitivity in human than in rat
      muscle homogenates, with approximately 15% autolysis observed after 1-min
      exposure to 2.5 microM Ca2+ in human muscle and almost none after 1- to 2-min
      exposure to the same [Ca2+]i level in rat muscle. During muscle activity, [Ca2+]i
      may transiently peak in the range found to autolyze mu-calpain and calpain-3, so
      we examined the effect of two types of exhaustive cycling exercise (30-s "all
      out" cycling, n = 8; and 70% VO2 peak until fatigue, n = 3) on the amount of
      autolyzed mu-calpain or calpain-3 in human muscle. No significant autolysis of mu
      calpain or calpain-3 occurred as a result of the exercise. These findings have
      shown that the time- and concentration-dependent changes in [Ca2+]i that occurred
      during concentric exercise fall near but below the level necessary to cause
      autolysis of calpains in vivo.

PMID- 16107504
TI  - Mitochondrial density determines the cellular sensitivity to cisplatin-induced
      cell death.
AB  - We studied the relationship between the mitochondrial density in the cells and
      the cellular sensitivity to the toxicity of cis-diaminedichloroplatinum II
      (cisplatin), a potent anticancer agent. Biochemical analyses revealed that the
      density of mitochondria in the intestinal epithelium changed markedly along its
      entire length. The density was the highest at the duodenum, medium at the
      jejunum, and the lowest at the ileum. The sensitivity of epithelial cells to
      cisplatin toxicity was the highest at the duodenum, medium at the jejunum, and
      the lowest at the ileum as judged from the occurrence of apoptosis. Similar
      correlation between the cisplatin sensitivity and mitochondrial density was also
      observed with in vitro experiments, in which intestinal epithelial cells (IEC-6)
      and their rho0 cells with reduced number of mitochondria were used. The rho0
      cells had a strong resistance to cisplatin compared with the control cells.
      Cisplatin markedly increased mitochondrial generation of reactive oxygen species
      in IEC-6 but not in rho0 cells. We analyzed the sensitivity of eight cell lines
      with different density of mitochondria to cisplatin and found the same positive
      correlation. These observations clearly show that cellular density of
      mitochondria is the key factor for the determination of the anticancer activity
      and side effects of cisplatin.

PMID- 16107505
TI  - Glucosamine inhibits angiotensin II-induced cytoplasmic Ca2+ elevation in
      neonatal cardiomyocytes via protein-associated O-linked N-acetylglucosamine.
AB  - We previously reported that glucosamine and hyperglycemia attenuate the response
      of cardiomyocytes to inositol 1,4,5-trisphosphate-generating agonists such as ANG
      II. This appears to be related to an increase in flux through the hexosamine
      biosynthesis pathway (HBP) and decreased Ca2+ entry into the cells; however, a
      direct link between HBP and intracellular Ca2+ homeostasis has not been
      established. Therefore, using neonatal rat ventricular myocytes, we investigated
      the relationship between glucosamine treatment; the concentration of UDP-N
      acetylglucosamine (UDP-GlcNAc), an end product of the HBP; and the level of
      protein O-linked N-acetylglucosamine (O-GlcNAc) on ANG II-mediated changes in
      intracellular free Ca2+ concentration ([Ca2+]i). We found that glucosamine
      blocked ANG II-induced [Ca2+]i increase and that this phenomenon was associated
      with a significant increase in UDP-GlcNAc and O-GlcNAc levels. O-(2-acetamido-2
      deoxy-D-glucopyranosylidene)-amino-N-phenylcarbamate, an inhibitor of O-GlcNAcase
      that increased O-GlcNAc levels without changing UDP-GlcNAc concentrations,
      mimicked the effect of glucosamine on the ANG II-induced increase in [Ca2+]i. An
      inhibitor of O-GlcNAc-transferase, alloxan, prevented the glucosamine-induced
      increase in O-GlcNAc but not the increase in UDP-GlcNAc; however, alloxan
      abrogated the inhibition of the ANG II-induced increase in [Ca2+]i. These data
      support the notion that changes in O-GlcNAc levels mediated via increased HBP
      flux may be involved in the regulation of [Ca2+]i homeostasis in the heart.

PMID- 16107506
TI  - Identification of AQP5 in lipid rafts and its translocation to apical membranes
      by activation of M3 mAChRs in interlobular ducts of rat parotid gland.
AB  - Aquaporin-5 (AQP5), an apical plasma membrane (APM) water channel in salivary
      glands, lacrimal glands, and airway epithelium, has an important role in fluid
      secretion. M(3) muscarinic acetylcholine receptor (mAChR)-induced changes in AQP5
      localization in rat parotid glands were investigated with immunofluorescence or
      immunoelectron microscopy, detergent solubility, and gradient density floatation
      assays. Confocal microscopy revealed AQP5 localization in intracellular vesicles
      of interlobular duct cells in rat parotid glands and AQP5 trafficking to the APM
      10 min after injection of the mAChR agonist cevimeline. Conversely, 60 min after
      injection, there was a diffuse pattern of AQP5 staining in the cell cytoplasm.
      The calcium ionophore A-23187 mimicked the effects of cevimeline. Immunoelectron
      microscopic studies confirmed that cevimeline induced AQP5 trafficking from
      intracellular structures to APMs in the interlobular duct cells of rat parotid
      glands. Lipid raft markers flotillin-2 and GM1 colocalized with AQP5 and moved
      with AQP5 in response to cevimeline. Under control conditions, the majority of
      AQP5 localized in the Triton X-100-insoluble fraction and floated to the light
      density fraction on discontinuous density gradients. After 10-min incubation of
      parotid tissue slices with cevimeline or A-23187, AQP5 levels decreased in the
      Triton X-100-insoluble fraction and increased in the Triton X-100-soluble
      fraction. Thus AQP5 localizes in the intracellular lipid rafts, and M(3) mAChR
      activation induces AQP5 trafficking to the APM with lipid rafts via intracellular
      Ca(2+) signaling and induces AQP5 dissociation from lipid rafts to nonrafts on
      the APM in the interlobular duct cells of rat parotid glands.

PMID- 16107507
TI  - Membrane cholesterol extraction decreases Na+ transport in A6 renal epithelia.
AB  - In this study, we have investigated the dependence of Na+ transport regulation on
      membrane cholesterol content in A6 renal epithelia. We continuously monitored
      short-circuit current (Isc), transepithelial conductance (GT), and
      transepithelial capacitance (CT) to evaluate the effects of cholesterol
      extraction from the apical and basolateral membranes in steady-state conditions
      and during activation with hyposmotic shock, oxytocin, and adenosine. Cholesterol
      extraction was achieved by perfusing the epithelia with methyl-beta-cyclodextrin
      (mbetaCD) for 1 h. In steady-state conditions, apical membrane cholesterol
      extraction did not significantly affect the electrophysiological parameters; in
      contrast, marked reductions were observed during basolateral mbetaCD treatment.
      However, apical mbetaCD application hampered the responses of Isc and GT to
      hypotonicity, oxytocin, and adenosine. Analysis of the blocker-induced
      fluctuation in Isc demonstrated that apical mbetaCD treatment decreased the
      epithelial Na+ channel (ENaC) open probability (Po) in the steady state as well
      as after activation of Na+ transport by adenosine, whereas the density of
      conducting channels was not significantly changed as confirmed by CT
      measurements. Na+ transport activation by hypotonicity was abolished during
      basolateral mbetaCD treatment as a result of reduced Na+/K+ pump activity. On the
      basis of the findings in this study, we conclude that basolateral membrane
      cholesterol extraction reduces Na+/K+ pump activity, whereas the reduced
      cholesterol content of the apical membranes affects the activation of Na+
      transport by reducing ENaC Po.

PMID- 16107508
TI  - EGF stimulates proliferation of mouse embryonic stem cells: involvement of Ca2+
      influx and p44/42 MAPKs.
AB  - We examined the effect of EGF on the proliferation of mouse embryonic stem (ES)
      cells and their related signal pathways. EGF increased [3H]thymidine and 5-bromo
      2'-deoxyuridine incorporation in a time- and dose-dependent manner. EGF
      stimulated the phosphorylation of EGF receptor (EGFR). Inhibition of EGFR
      tyrosine kinase with AG-1478 or herbimycin A, inhibition of PLC with neomycin or
      U-73122, inhibition of PKC with bisindolylmaleimide I or staurosporine, and
      inhibition of L-type Ca2+ channels with nifedipine or methoxyverapamil prevented
      EGF-induced [3H]thymidine incorporation. PKC-alpha, -betaI, -gamma, -delta, and 
      zeta were translocated to the membrane and intracellular Ca2+ concentration
      ([Ca2+]i) was increased in response to EGF. Moreover, inhibition of EGFR tyrosine
      kinase, PLC, and PKC completely prevented EGF-induced increases in [Ca2+]i. EGF
      also increased inositol phosphate levels, which were blocked by EGFR tyrosine
      kinase inhibitors. Furthermore, EGF rapidly increased formation of H2O2, and
      pretreatment with antioxidant (N-acetyl-L-cysteine) inhibited EGF-induced
      increase of [Ca2+]i. In addition, we observed that p44/42 MAPK phosphorylation by
      EGF and inhibition of EGFR tyrosine kinase, PLC, PKC, or Ca2+ channels blocked
      EGF-induced phosphorylation of p44/42 MAPKs. Inhibition of p44/42 MAPKs with PD
      98059 (MEK inhibitor) attenuated EGF-induced increase of [3H]thymidine
      incorporation. Finally, inhibition of EGFR tyrosine kinase, PKC, Ca2+ channels,
      or p44/42 MAPKs attenuated EGF-stimulated cyclin D1, cyclin E, cyclin-dependent
      kinase (CDK)2, and CDK4, respectively. In conclusion, EGF partially stimulates
      proliferation of mouse ES cells via PLC/PKC, Ca2+ influx, and p44/42 MAPK signal
      pathways through EGFR tyrosine kinase phosphorylation.

PMID- 16107509
TI  - Lung endothelial cell proliferation with decreased shear stress is mediated by
      reactive oxygen species.
AB  - Acute cessation of flow (ischemia) leads to depolarization of the endothelial
      cell (EC) membrane mediated by K(ATP) channels and followed by production of
      reactive oxygen species (ROS) from NADPH oxidase. We postulated that ROS are a
      signal for initiating EC proliferation associated with the loss of shear stress.
      Flow cytometry was used to identify proliferating CD31-positive pulmonary
      microvascular endothelial cells (mPMVECs) from wild-type, Kir6.2-/-, and gp91phox
      /- mice. mPMVECs were labeled with PKH26 and cultured in artificial capillaries
      for 72 h at 5 dyn/cm2 (flow adaptation), followed by 24 h of stop flow or
      continued flow. ROS production during the first hour of ischemia was markedly
      diminished compared with wild-type mice in both types of gene-targeted mPMVECs.
      Cell proliferation was defined as the proliferation index (PI). After 72 h of
      flow, >98% of PKH26-labeled wild-type mPMVECs were at a single peak (PI 1.0) and
      the proportion of cells in the S+G2/M phases were at 5.8% on the basis of cell
      cycle analysis. With ischemia (24 h), PI increased to 2.5 and the ratio of cells
      in S+G2/M phases were at 35%. Catalase, diphenyleneiodonium, and cromakalim
      markedly inhibited ROS production and cell proliferation in flow-adapted wild
      type mPMVECs. Significant effects of ischemia were not observed in Kir6.2-/- and
      gp91phox-/- cells. ANG II activation of NADPH oxidase was unaffected by KATP gene
      deletion. Thus loss of shear stress in flow-adapted mPMVECs results in cell
      division associated with ROS generated by NADPH oxidase. This effect requires a
      functioning cell membrane KATP channel.

PMID- 16107510
TI  - Evoked potential studies in the antiphospholipid syndrome: differential diagnosis
      from multiple sclerosis.
AB  - BACKGROUND: The CNS manifestations of the antiphospholipid syndrome (APS) can
      mimic multiple sclerosis both clinically and radiologically. OBJECTIVE: To
      compare evoked potential studies in APS patients and patients with multiple
      sclerosis with similar neurological disability. METHODS: 30 APS patients with CNS
      manifestations and 33 patients with definite multiple sclerosis and similar
      neurological disability underwent studies of visual evoked potentials (VEP),
      somatosensory evoked potentials (SSEP) in the upper and lower limbs (UL, LL), and
      sympathetic skin responses (SSR) in the upper and lower limbs. RESULTS: The
      neurological manifestations in the APS patients included stroke (n = 17),
      transient ischaemic attacks (n = 10), and severe headache with multiple white
      matter lesions on brain MRI (n = 3). Abnormal SSEP (LL), and SSR (UL; LL) were
      seen in APS patients (37%, 27%, and 30%, respectively) but VEP and UL SSEP were
      rarely abnormal (10% and 6%, respectively in APS v 58% and 33% in multiple
      sclerosis; p = 0.0005, p = 0.008). Mean VEP latencies were more prolonged in
      multiple sclerosis (116 ms v 101 ms, p<0.001). Only one APS patient had abnormal
      findings in all three evoked potential studies, compared with seven patients in
      the multiple sclerosis group (p = 0.04) CONCLUSIONS: Abnormal VEPs are uncommon
      in APS in contrast to multiple sclerosis. Coexisting abnormalities in all other
      evoked potentials were similarly rare in APS. In patients with brain MRI findings
      compatible either with multiple sclerosis or APS, normal evoked potential tests,
      and especially a normal VEP, may support the diagnosis of APS.

PMID- 16107511
TI  - MHC class II, tumour necrosis factor alpha, and lymphotoxin alpha gene haplotype
      associations with serological subsets of systemic lupus erythematosus.
AB  - OBJECTIVE: To conduct a case-control study to investigate whether there are
      independent tumour necrosis factor alpha (TNFalpha) or lymphotoxin alpha
      (LTalpha) haplotype associations with SLE or with any of the major serological
      subsets of SLE. METHODS: 157 patients with SLE were genotyped for HLA-DRB1, HLA
      DQB1, TNFalpha, and LTalpha alleles by polymerase chain reaction and compared
      with 245 normal white controls. For TNFalpha, six single nucleotide polymorphisms
      (SNPs) at positions -1031, -863, -857, -308, -238, and +488 and for LTalpha three
      SNPs at positions +720, +365, and +249 were studied to assign six TNFalpha
      haplotypes (TNF1-6) and four LTalpha haplotypes (LTA1-4). All SLE patients had
      full serological profiles on serial samples. RESULTS: The most significant
      association with SLE overall was with HLA-DR3 (p<0.001; odds ratio (OR) = 2.5
      (95% confidence interval, 1.6 to 3.8)) and the extended haplotype HLA
      DQB1*0201;DRB1*0301;TNF2;LTA2 (p<0.001; OR = 2.3 (1.4 to 3.7)). Associations were
      strongest in the anti-La positive group (13%) of SLE patients (HLA-DR3, OR = 71
      (9 to 539); HLA-DQB1*0201, OR = 35 (5 to 267); TNF2, OR = 10 (2.8 to 36), and
      LTA2, OR = 4.9 (1.1 to 21)). There was an increase in the HLA-DR2 associated
      extended haplotype (HLA-DQB1*0602;DRB1*1501;TNF1;LTA1) in patients with anti-Ro
      in the absence of anti-La (p<0.005; OR = 3.9 (1.5 to 10)). The HLA-DR7 extended
      haplotype (HLA-DQB1*0303;DRB1*0701/2;TNF5;LTA3) was decreased in SLE overall
      (p<0.02; OR = 0.2 (0.05 to 0.8)). CONCLUSIONS: The strongest association in this
      predominantly white population with SLE was between HLA-DR3 and anti-La, which
      seemed to account for any associations with TNFalpha alleles on an extended DR3
      haplotype.

PMID- 16107512
TI  - Is progressive osteoarthritis an atheromatous vascular disease?
AB  - Growing evidence from epidemiological studies suggests that osteoarthritis (OA)
      is linked to atheromatous vascular disease. This hypothesis article proposes that
      OA, or at least OA structural progression, may be an atheromatous vascular
      disease of subchondral bone. Further epidemiological studies, imaging
      investigations of relevant blood vessels, and trials of the effects of statins on
      the prevention and treatment of OA are needed to examine this hypothesis.

PMID- 16107514
TI  - Chemokine and chemokine receptor expression in paired peripheral blood
      mononuclear cells and synovial tissue of patients with rheumatoid arthritis,
      osteoarthritis, and reactive arthritis.
AB  - BACKGROUND: Chemokine receptors and chemokines have a crucial role in leucocyte
      recruitment into inflamed tissue. OBJECTIVE: To examine the expression of an
      extensive number of chemokines and receptors in a unique bank of paired samples
      of synovial tissue (ST) and peripheral blood (PB) from patients with different
      forms of arthritis to assist in identifying suitable targets for therapeutic
      intervention. METHODS: Synovial biopsy specimens were obtained from 23 patients
      with rheumatoid arthritis (RA), 16 with osteoarthritis, and 8 with reactive
      arthritis. ST chemokine (CCL2/MCP-1, CCL5/RANTES, CCL7/MCP-3, CCL8/MCP-2,
      CCL14/HCC-1, CCL15/HCC-2, CCL16/HCC-4), chemokine receptor (CCR1, CCR2b, CCR5,
      CXCR4), and CD13 expression was analysed by immunohistochemistry and two colour
      immunofluorescence. Chemokine receptor expression (CCR1, CCR3, CCR5, CCR6, CCR7)
      on PB cells was studied by flow cytometry. Non-parametric tests were used for
      statistical analysis. RESULTS: Abundant expression of CCR1, CXCR4, and CCR5 was
      found in all forms of arthritis, with a specific increase of CCL5 and CCL15 in
      RA. CCL7, CCL8, CCL14, CCL15, and CCL16 were detected for the first time in ST.
      The results for PB analysis were comparable among different arthritides.
      Interestingly, compared with healthy controls, significantly lower expression of
      CCR1 (p<0.005) and CCR5 (p<0.05) by PB monocytes in the patient groups was seen.
      DISCUSSION: A variety of chemokines and receptors might have an important role in
      several inflammatory joint disorders. Although other receptors are involved as
      well, migration of CCR1(+) and CCR5(+) cells towards the synovial compartment may
      play a part in the effector phase of various forms of arthritis.

PMID- 16107513
TI  - Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published
      evidence and prospective trial data.
AB  - Adverse effects of glucocorticoids have been abundantly reported. Published
      reports on low dose glucocorticoid treatment show that few of the commonly held
      beliefs about their incidence, prevalence, and impact are supported by clear
      scientific evidence. Safety data from recent randomised controlled clinical
      trials of low dose glucocorticoid treatment in RA suggest that adverse effects
      associated with this drug are modest, and often not statistically different from
      those of placebo.

PMID- 16107515
TI  - Aberrant TNF secretion by whole blood in healthy subjects with a history of
      reactive arthritis: time course in adherent and non-adherent cultures.
AB  - BACKGROUND: The pathogenesis of reactive arthritis (ReA) apparently involves
      aberrations in innate immune functions such as monocyte tumour necrosis factor
      (TNF) generation. OBJECTIVE: To investigate TNF production in healthy subjects
      with previous yersinia triggered reactive arthritis. METHODS: The study comprised
      HLA-B27 positive subjects with previous reactive arthritis (B27+ReA+), and
      B27+ReA- and B27-ReA- subjects (n = 15 each). Whole blood TNF production was
      induced by lipopolysaccharide (LPS), which binds to CD14/TLR4 on the monocyte
      surface, or by a combination of phorbol 12-myristate 13-acetate (PMA) and Ca(2+)
      ionophore A23187, which activates monocytes independently of cell surface
      receptors. To further evaluate the possible role of adhesion mediated signalling
      on TNF production, blood samples were incubated in adherent or non-adherent
      conditions. TNF levels in culture supernatants were measured using an automated
      immunoassay analyser. The CD14(-159)C/T genotype was determined by a cycle
      minisequencing method. RESULTS: B27+ReA+ supernatants had higher TNF levels than
      B27+ReA- supernatants in PMA/A23187 wells in two hour (p = 0.004) and four hour
      cultures (p = 0.001). Rapid initial TNF release took place in adherent but not in
      non-adherent conditions. This adhesion associated difference was greater in the
      B27+ReA+ group than in the B27+ReA- or B27-ReA- group in response to PMA/A23187
      (p values <0.001), and greater in the B27+ReA+ group than in the B27-ReA- group
      in response to LPS (p = 0.021). CD14(-159)T was associated allele dose
      dependently with an increase in the LPS induced TNF secretion allele (p = 0.030).
      CONCLUSIONS:  SUBJECTS: who have recovered from yersinia arthritis show enhanced
      TNF production, which may be regulated at the level of monocyte adhesion.

PMID- 16107516
TI  - Evans blue is a specific antagonist of the human epithelial Na+ channel delta
      subunit.
AB  - The epithelial Na(+) channel (ENaC) regulates Na(+) homeostasis in cells and
      across epithelia. Four homologous ENaC subunits (alpha, beta, gamma, and delta)
      have been isolated in mammals. Combination of alpha-, beta-, and gamma-subunits
      or delta-, beta-, and gamma-subunits forms fully functional channels. Amiloride
      is a well known blocker of the ENaC family that inhibits both channel complexes.
      However, no specific antagonists are currently known that distinguish them. Here,
      we show that Evans blue, a diagnostic aid for the measurement of blood volume and
      vascular permeability, inhibits the activity of the delta-subunit expressed in
      Xenopus oocytes. The inward currents at a holding potential of -60 mV in human
      ENaCdeltabetagamma-expressing oocytes were inhibited by the application of Evans
      blue in a concentration-dependent manner with an IC(50) value of 143 muM. Evans
      blue markedly inhibited the delta-subunit current but did not block the alpha
      subunit current. In conclusion, Evans blue is the first known delta-subunit
      specific antagonist of ENaC. This finding provides us with a key compound for
      elucidating the physiological and pathological functions of ENaCdelta in humans
      and for drug development in the ENaC family.

PMID- 16107517
TI  - PEPT2 (Slc15a2)-mediated unidirectional transport of cefadroxil from
      cerebrospinal fluid into choroid plexus.
AB  - Cefadroxil is a cephalosporin antibiotic used in the treatment of infection.
      However, cerebrospinal fluid (CSF) concentrations of cefadroxil and other
      aminocephalosporins are not adequate for the treatment of bacterial meningitis.
      To evaluate the relevance of PEPT2 in affecting the exposure of
      aminocephalosporins in brain, we investigated the transport properties of
      cefadroxil at the blood-CSF interface using primary-cultured epithelial cells and
      isolated whole tissues of choroid plexus. Our results indicated that cefadroxil
      was preferentially taken up from the apical as opposed to basal side of the
      monolayer (5-fold), and its apical uptake was stimulated by an inwardly directed
      proton gradient. The concentration-dependent apical uptake of cefadroxil was
      characterized by a high-affinity/low-capacity transport system (Km = 39.0 +/-
      22.7 microM; Vmax = 22.9 +/- 6.6 pmol/mg/min) and a nonsaturable component (Kd =
      0.15 +/- 0.01 microl/mg/min); in contrast, only a nonsaturable component was
      found for the basal uptake of cefadroxil (Kd = 0.14 +/- 0.01 microl/mg/min). The
      apical-to-basal transepithelial transport of 2 microM cefadroxil was greater than
      its basal-to-apical transport, but no differences were observed in directionality
      when 5 mM concentrations of cefadroxil were studied. Moreover, the cellular
      efflux of cefadroxil was not saturable in either direction (i.e., to apical or
      basal side). Finally, no differences were observed in the choroid plexus tissue
      efflux of 2 microM cefadroxil from wild-type and PEPT2 null mice. These findings
      demonstrate that PEPT2 has an important role in limiting the exposure of
      cefadroxil in CSF. Located at the apical membrane of choroid plexus epithelium,
      PEPT2 acts in a unidirectional (as opposed to bidirectional) manner in
      transporting cefadroxil from CSF into the cell.

PMID- 16107518
TI  - An odorant-binding protein facilitates odorant transfer from air to hydrophilic
      surroundings in the blowfly.
AB  - Chemical sense-related lipophilic ligand-binding protein (CRLBP) is an insect
      odorant-binding protein (OBP) found abundantly in the taste and olfactory organs
      of the blowfly, Phormia regina. Through computational construction, a three
      dimensional molecular model of a CRLBP indicated good fitting to a fluorescent
      ligand, 7-hydroxycoumarin (7-HC), in its ligand-binding pocket. By showing that
      the fluorescence of 7-HC bound to CRLBP migrated in a native electrophoresis gel,
      we confirmed that CRLBP formed a stable complex with 7-HC. In an odorant-binding
      experiment, 7-HC vapor odor was introduced by aeration to the aquatic solution
      containing CRLBP and its binding to CRLBP fluorospectrometrically quantified.
      Because olfactory organs as well as taste organs of flies respond to vapors, we
      suggest that CRLBP effectively transfers odorants from the air into aquatic
      surroundings by forming stable complexes with airborne molecules in both
      chemosensory organs.

PMID- 16107519
TI  - Gaze orienting in dynamic visual double steps.
AB  - Visual stimuli are initially represented in a retinotopic reference frame. To
      maintain spatial accuracy of gaze (i.e., eye in space) despite intervening eye
      and head movements, the visual input could be combined with dynamic feedback
      about ongoing gaze shifts. Alternatively, target coordinates could be updated in
      advance by using the preprogrammed gaze-motor command ("predictive remapping").
      So far, previous experiments have not dissociated these possibilities. Here we
      study whether the visuomotor system accounts for saccadic eye-head movements that
      occur during target presentation. In this case, the system has to deal with fast
      dynamic changes of the retinal input and with highly variable changes in relative
      eye and head movements that cannot be preprogrammed by the gaze control system.
      We performed visual-visual double-step experiments in which a brief (50-ms)
      stimulus was presented during a saccadic eye-head gaze shift toward a previously
      flashed visual target. Our results show that gaze shifts remain accurate under
      these dynamic conditions, even for stimuli presented near saccade onset, and that
      eyes and head are driven in oculocentric and craniocentric coordinates,
      respectively. These results cannot be explained by a predictive remapping scheme.
      We propose that the visuomotor system adequately processes dynamic changes in
      visual input that result from self-initiated gaze shifts, to construct a stable
      representation of visual targets in an absolute, supraretinal (e.g., world)
      reference frame. Predictive remapping may subserve transsaccadic integration,
      thus enabling perception of a stable visual scene despite eye movements, whereas
      dynamic feedback ensures accurate actions (e.g., eye-head orienting) to a
      selected goal.

PMID- 16107520
TI  - Self-triggered functional electrical stimulation during swallowing.
AB  - Hyolaryngeal elevation is essential for airway protection during swallowing and
      is mainly a reflexive response to oropharyngeal sensory stimulation. Targeted
      intramuscular electrical stimulation can elevate the resting larynx and, if
      applied during swallowing, may improve airway protection in dysphagic patients
      with inadequate hyolaryngeal motion. To be beneficial, patients must synchronize
      functional electrical stimulation (FES) with their reflexive swallowing and not
      adapt to FES by reducing the amplitude or duration of their own muscle activity.
      We evaluated the ability of nine healthy adults to manually synchronize FES with
      hyolaryngeal muscle activity during discrete swallows, and tested for motor
      adaptation. Hooked-wire electrodes were placed into the mylo- and thyrohyoid
      muscles to record electromyographic activity from one side of the neck and
      deliver monopolar FES for hyolaryngeal elevation to the other side. After
      performing baseline swallows, volunteers were instructed to trigger FES with a
      thumb switch in synchrony with their swallows for a series of trials. An
      experimenter surreptitiously disabled the thumb switch during the final attempt,
      creating a foil. From the outset, volunteers synchronized FES with the onset of
      swallow-related thyrohyoid activity (approximately 225 ms after mylohyoid
      activity onset), preserving the normal sequence of muscle activation. A
      comparison between average baseline and foil swallows failed to show significant
      adaptive changes in the amplitude, duration, or relative timing of activity for
      either muscle, indicating that the central pattern generator for hyolaryngeal
      elevation is immutable with short term stimulation that augments laryngeal
      elevation during the reflexive, pharyngeal phase of swallowing.

PMID- 16107521
TI  - Background changes delay the perceptual availability of form information.
AB  - In natural visual situations, unlike most psychophysical experiments, when a new
      stimulus appears in a portion of the visual field, the surrounding background
      changes simultaneously. In recordings from macaque V1, we found that a visual
      stimulus presented simultaneously with a background change evokes a response that
      is qualitatively different from the response to the same stimulus flashed on a
      static background. With the changing background, information about stimulus
      orientation and contrast is significantly delayed compared with the static
      background situation. Our physiological results make several predictions that we
      test in the present paper with human psychophysical experiments. In a backward
      masking paradigm, a bar stimulus was either flashed onto a static background or
      presented simultaneously with a change in background luminance or pattern.
      Subjects discriminated bar orientation or detected that the scene changed before
      the mask. To achieve an equivalent contrast threshold for orientation
      discrimination, a longer stimulus-mask onset asynchrony (SOA) was needed in the
      changing than in the static-background condition; to match the orientation
      discrimination performance in the static and changing-background conditions at a
      fixed SOA, a higher bar contrast was needed when the background changed.
      Moreover, in the changing-background condition, a longer SOA was needed to
      discriminate bar orientation than to detect the scene change. These results
      suggest that orientation information is available more slowly when the background
      changes; orientation information is available earlier as stimulus contrast
      increases. The psychophysical findings are consistent with our physiological
      predictions. Compared with the common technique of flashing stimuli onto a static
      background, the changing-background paradigm may be more similar to natural
      vision in which saccades bring new stimuli and backgrounds into the visual field.

PMID- 16107522
TI  - Background changes delay information represented in macaque V1 neurons.
AB  - In natural behavioral situations, saccadic eye movements not only introduce new
      stimuli into V1 receptive fields, they also cause changes in the background. We
      recorded in awake macaque V1 using a fixation paradigm and compared evoked
      activity to small stimuli when the background was either static or changing as
      with a saccade. When a stimulus was shown on a static background, as in most
      previous experiments, the initial response was orientation selective and contrast
      was inversely correlated with response latency. When a stimulus was introduced
      with a background change, V1 neurons showed a qualitatively different temporal
      response pattern in which information about stimulus orientation and contrast was
      delayed. The delay in the representation of visual information was found with
      three different types of background change-luminance increment, luminance
      decrement, and a pattern change with fixed mean luminance. We also found that
      with a background change, V1 off responses were suppressed and had a shorter time
      course compared with the static-background situation. Our results suggest that
      the distribution of temporal changes across the visual field plays a fundamental
      role in determining V1 responses. In the static-background condition, temporal
      change in the visual input occurs only in a small portion of the visual field. In
      the changing-background condition, and presumably in natural vision, temporal
      changes are widely distributed. Thus a delayed representation of visual
      information may be more representative of natural visual situations.

PMID- 16107523
TI  - Effects of delta-conotoxins PVIA and SVIE on sodium channels in the amphibian
      sympathetic nervous system.
AB  - delta-Conotoxins are a family of small, disulfide-rich peptides found in the
      venoms of predatory cone snails (Conus). We examined in detail the effects of
      delta-conotoxin PVIA from the fish hunting cone snail Conus purpurascens on
      sodium currents in dissociated sympathetic neurons from the leopard frog Rana
      pipiens. We also compared this toxin's effects with those of delta-conotoxin SVIE
      from Conus striatus, another piscivorous cone snail. d-PVIA slowed the time
      course of inactivation of delta sodium currents and shifted the voltage
      dependence of activation and steady-state inactivation to more hyperpolarized
      potentials. Similar, albeit more pronounced, effects were seen with d-SVIE. While
      the effects of d-PVIA were reversed by washing, those of d-SVIE were largely
      irreversible over the time-course of these experiments. The effects of d-PVIA
      could be suppressed by conditioning depolarizations in a voltage- and time
      dependent manner, whereas the effects of d-SVIE were largely resistant to
      conditioning depolarizations. Last, in intact sympathetic nervous system
      preparations, d-PVIA inhibited evoked trains of compound action potentials. Many
      of these effects of d-PVIA and d-SVIE are remarkably similar to those of toxins
      that bind to site 3 on voltage-gated sodium channels.

PMID- 16107524
TI  - Proportion of N-type calcium current activated by action potential stimuli.
AB  - N-type calcium currents are important in many neuronal functions, including
      cellular signaling, regulation of gene expression, and triggering of
      neurotransmitter release. Often the control of these diverse cellular functions
      is governed by the spatial and temporal patterns of calcium entry in subcellular
      compartments. Underlying this issue is the effectiveness of action potentials at
      triggering calcium channel opening. Chick ciliary ganglion neurons were used as
      model cells to study the activation of N-type calcium current during action
      potential depolarization. Several different action potential shapes were
      recorded, used as voltage command templates, and altered such that control action
      potential-evoked currents could be compared with those elicited by broadened
      action potential commands. Depending on the action potential shape used to
      activate calcium currents in chick ciliary ganglion neurons, and the temperature
      at which recordings were performed, varying proportions (I/I(max)) of N-type
      calcium current could be activated. The largest proportion measured occurred
      using a broad ciliary ganglion cell soma action potential to activate calcium
      current at 37 degrees C (100%). The smallest proportion measured occurred using a
      fast, high-temperature-adjusted frog motoneuron nerve terminal action potential
      to activate calcium current at room temperature (10%). These data are discussed
      with respect to the impact on cellular signaling and the regulation of
      transmitter release.

PMID- 16107525
TI  - Imaging of Ca2+ dynamics within the presynaptic terminals of salamander rod
      photoreceptors.
AB  - Although the overall importance of Ca(2+) as a mediator of cell signaling and
      neurotransmitter release has long been appreciated, the details of Ca(2+)
      dynamics within the inner segments of vertebrate rod photoreceptors are just
      beginning to be elucidated. Even less is known regarding Ca(2+) dynamics within
      the rod presynaptic terminal compartment. Using fura-2 to report changes in
      intracellular Ca(2+), we imaged the responses of enzymatically dissociated
      salamander rod photoreceptors retaining intact axons and presynaptic terminals
      stimulated with a brief depolarizing puff of KCl (30 mM pipette concentration).
      In the vast majority of cells, the response was a large increase in Ca(2+) levels
      in the terminal compartment, but not in the soma. In contrast, rods exhibited a
      substantial elevation in somatic Ca(2+) levels when depolarized with a brief puff
      of 100 mM KCl (pipette concentration). These data are consistent with previously
      reported differences in Ca(2+) buffering mechanisms within the somatic and
      terminal compartments. Additionally, they may reflect the presence of Ca(2+)
      channels having distinct properties within the membranes of the two compartments.
      Consistent with this hypothesis, fluorescent immunocytochemistry using an
      antibody against the L-type Ca(2+) channel Ca(v)1.2 (alpha1C) subunit and
      semiquantitative confocal microscopy revealed a high concentration of
      immunoreactivity in the membranes of terminals of intact rods compared with the
      somata. Further investigations using enzymatically dissociated preparations of
      intact rod photoreceptors retaining their presynaptic terminals will allow
      further testing of these and other hypotheses regarding the compartmentalized
      regulation of Ca(2+) dynamics within rod photoreceptors.

PMID- 16107526
TI  - SK channel regulation of dendritic excitability and dendrodendritic inhibition in
      the olfactory bulb.
AB  - Small-conductance calcium-activated potassium channels (SK) regulate dendritic
      excitability in many neurons. In the olfactory bulb, regulation of
      backpropagating action potentials and dendrodendritic inhibition depend on the
      dendritic excitability of mitral cells. We report here that SK channel currents
      are present in mitral cells but are not detectable in granule cells in the
      olfactory bulb. In brain slices from PND 14-21 mice, long step depolarizations
      (100 ms) in the mitral cell soma evoked a cadmium- and apamin-sensitive outward
      SK current lasting several hundred milliseconds. Block of the SK current unmasked
      an inward N-methyl-D-aspartate (NMDA) autoreceptor current due to glutamate
      released from mitral cell dendrites. In low extracellular Mg(2+) (100 microM),
      brief step depolarizations (2 ms) evoked an apamin-sensitive current that was
      reduced by D,L-2-amino-5-phosphonopentanoic acid. In current- clamp, block of SK
      channels increased action potential firing in mitral cells as well as
      dendrodendritic inhibition. Our results indicate that SK channels can be
      activated either by calcium channels or NMDA channels in mitral cell dendrites,
      providing a mechanism for local control of dendritic excitability.

PMID- 16107527
TI  - Neural representation of bitter taste in the nucleus of the solitary tract.
AB  - Based on the molecular findings that many bitter taste receptors (T2Rs) are
      expressed within the same receptor cells, it has been proposed that bitter taste
      is encoded by the activation of discrete neural elements. Here we examined how a
      variety of bitter stimuli are represented by neural activity in central gustatory
      neurons. Taste responses (spikes/s) evoked by bathing the tongue and palate with
      intensity-matched concentrations (in M) of 2 sugars (0.32 sucrose and 0.5 D
      fructose), ethanol (40%), 4 salts (0.01 NaCl, 0.008 NaNO(3), 0.01 MgCl(2), and
      0.05 KCl), 2 acids (0.003 HCl and 0.005 citric acid), and 10 bitter ligands
      (0.007 quinine-HCl, 0.015 denatonium benzoate, 0.003 l-cysteine, 0.001 nicotine,
      0.005 strychnine-HCl, 0.04 tetraethylammonium chloride, 0.03 atropine-SO(4),
      0.005 brucine-SO(4), 0.03 papaverine-HCl, and 0.009 sparteine) were recorded from
      51 neurons in the nucleus of the solitary tract of anesthetized rats. Cluster
      analysis was used to categorize neurons into types based on responses to sucrose,
      NaCl, HCl, and quinine-HCl. Three groupings emerged: type S (responded optimally
      to sweets), type N (sodium-optimal), and type H/Q (responded robustly to bitters,
      acids, and salts). Multivariate analyses revealed that across-neuron patterns of
      response among bitter stimuli were strongly correlated. However, neural type H/Q,
      which was most responsive to bitter tastants, was not differentially sensitive to
      bitter stimuli and Na(+) salts, which rats perceive as distinct. Thus central
      neurons most responsive to bitter substances receive significant input from
      receptors that mediate other tastes, indicating that bitter stimuli are not
      represented by activity in specifically tuned neurons.

PMID- 16107528
TI  - Implied motion from form in the human visual cortex.
AB  - When cartoonists use speed lines--also called motion streaks--to suggest the
      speed of a stationary object, they use form to imply motion. The goal of this
      study was to investigate the mechanisms that mediate the percept of implied
      motion in the human visual cortex. In an adaptation functional imaging paradigm
      we presented Glass patterns that, just like speed lines, imply motion but do not
      on average contain coherent motion energy. We found selective adaptation to these
      patterns in the human motion complex, the lateral occipital complex (LOC), and
      earlier visual areas. Glass patterns contain both local orientation features and
      global structure. To disentangle these aspects we performed a control experiment
      using Glass patterns with minimal local orientation differences but large global
      structure differences. This experiment showed that selectivity for Glass patterns
      arises in part in areas beyond V1 and V2. Interestingly, the selective adaptation
      transferred from implied motion stimuli to similar real motion patterns in dorsal
      but not ventral areas. This suggests that the same subpopulations of cells in
      dorsal areas that are selective for implied motion are also selective for real
      motion. In other words, these cells are invariant with respect to the cue
      (implied or real) that generates the motion. We conclude that the human motion
      complex responds to Glass patterns as if they contain coherent motion. This,
      presumably, is the reason why these patterns appear to move coherently. The LOC,
      however, has different cells that respond to the structure of real motion
      patterns versus implied motion patterns. Such a differential response may allow
      ventral areas to further analyze the structure of global patterns.

PMID- 16107529
TI  - Excitatory actions of dopamine via D1-like receptors in the rat lateral
      geniculate nucleus.
AB  - The excitability of relay neurons in the dorsal geniculate nucleus (dLGN) can be
      altered by a variety of neuromodulators. The dLGN receives substantial
      dopaminergic input from the brain stem, and this innervation may play a crucial
      role in the gating of visual information from the retina to visual neocortex. In
      this study, we investigated the action of dopamine on identified dLGN neurons
      using whole cell recording techniques. Dopamine (2-200 microM) produced a
      membrane depolarization in >95% of relay neurons tested but did not alter
      excitability of dLGN interneurons. The D1-like dopamine receptor agonist SKF38393
      (2-50 microM) produced a similar depolarization in dLGN relay neurons. However,
      the D2-like receptor agonists, bromocriptine (25-50 microM) and PPHT (1-50
      microM), did not alter the membrane potential of relay neurons. SCH23390 (5-10
      microM), a D1-like receptor antagonist, attenuated the depolarizing actions of
      both dopamine and SKF38393. Furthermore, the excitatory actions of dopamine and
      SKF38393 were attenuated by ZD7288, a specific antagonist for the
      hyperpolarization activated mixed cation current, I(h). Our data suggest that
      dopamine, acting via D1-like receptors, activates I(h) leading to a membrane
      depolarization. Through the modulation of dLGN neuronal excitability, ascending
      and descending activating systems may not only control the state of the thalamus
      such as the transition from slow-wave sleep to waking but also regulate the
      efficacy of information transfer during waking states.

PMID- 16107530
TI  - Stimulus induced desynchronization of human auditory 40-Hz steady-state
      responses.
AB  - The hypothesis that gamma-band oscillations are related to the representation of
      an environmental scene in the cerebral cortex after binding of corresponding
      perceptual elements is currently under discussion. One question is how the
      sensory system reacts to a fast change in the scene if perceptual elements are
      rigidly bound together. A reset of the gamma-band oscillation forced by a change
      in sensory input may dissolve the binding, which then would be re-established for
      the new sensation. We studied the reset of gamma-band oscillations on the 40-Hz
      auditory steady-state responses (ASSR) by means of whole-head
      magnetoencephalography (MEG). The rhythm of 40-Hz AM of a 500-Hz tone evoked the
      ASSR, and a short noise burst served as a concurrent stimulus. Possible direct
      interactions of the auditory stimuli were excluded by presenting the noise
      impulse in a different frequency channel (2,000-3,000 Hz) to the contralateral
      ear. The concurrent stimulus induced a considerable decrement in the amplitude of
      ASSR, which was localized in primary auditory cortices. This decrement lasted 250
      ms and was significantly longer than the duration of the transient gamma-band
      response evoked by the noise burst. Thus it could not be explained by any linear
      superimposition of the responses. The time courses of ASSR amplitude and phase
      during recovery from the decrement resembled those after stimulus onset,
      indicating that a new ASSR was built up after the resetting stimulus. The results
      are discussed as reset of oscillations in human thalamocortical networks.

PMID- 16107531
TI  - Silent synapses in a thalamo-cortical circuit necessary for song learning in
      zebra finches.
AB  - Developmental changes in synaptic properties may act to limit neural and
      behavioral plasticity associated with sensitive periods. This study characterized
      synaptic maturation in a glutamatergic thalamo-cortical pathway that is necessary
      for vocal learning in songbirds. Lesions of the projection from medial
      dorsolateral nucleus of the thalamus (DLM) to the cortical nucleus lateral
      magnocellular nucleus of the anterior nidopallium (LMAN) greatly disrupt song
      behavior in juvenile birds during early stages of vocal learning. However, such
      lesions lose the ability to disrupt vocal behavior in normal birds at 60-70 days
      of age, around the time that selective auditory tuning for each bird's own song
      (BOS) emerges in LMAN neurons. This pattern has suggested that LMAN is involved
      in processing song-related information and evaluating the degree to which vocal
      motor output matches the tutor song to be learned. Analysis of reversed
      excitatory postsynaptic currents at DLM-->LMAN synapses in in vitro slice
      preparations revealed a pronounced N-methyl-D-aspartate receptor (NMDAR)-mediated
      component in both juvenile and adult cells with no developmental decrease in the
      relative contribution of NMDARs to synaptic transmission. However, the synaptic
      failure rate at DLM-->LMAN synapses in juvenile males during the sensitive period
      for song learning was significantly lower at depolarized potentials than at
      hyperpolarized potentials. In contrast, the failure rate at DLM-->LMAN synapses
      did not differ at hyper- versus depolarized holding potentials in adult males
      that had completed the acquisition of a stereotyped song. This pattern indicates
      that juvenile cells have a higher incidence of silent (NMDAR-only) synapses,
      which are postsynaptically silent at hyperpolarized potentials due to the voltage
      dependent gating of NMDARs. Thus the decreased involvement of the LMAN pathway in
      vocal behavior is mirrored by a decline in the incidence of silent synapses but
      not by changes in the relative number of NMDA and AMPA receptors at DLM-->LMAN
      synapses. These findings suggest that a developmental decrease in silent synapses
      within LMAN may represent a neural correlate of behavioral plasticity during song
      learning.

PMID- 16107532
TI  - Nicotinic acetylcholine receptor subtypes involved in facilitation of GABAergic
      inhibition in mouse superficial superior colliculus.
AB  - The superficial superior colliculus (sSC) is a key station in the sensory
      processing related to visual salience. The sSC receives cholinergic projections
      from the parabigeminal nucleus, and previous studies have revealed the presence
      of several different nicotinic acetylcholine receptor (nAChR) subunits in the
      sSC. In this study, to clarify the role of the cholinergic inputs to the sSC, we
      examined current responses induced by ACh in GABAergic and non-GABAergic sSC
      neurons using in vitro slice preparations obtained from glutamate decarboxylase
      67-green fluorescent protein (GFP) knock-in mice in which GFP is specifically
      expressed in GABAergic neurons. Brief air pressure application of acetylcholine
      (ACh) elicited nicotinic inward current responses in both GABAergic and non
      GABAergic neurons. The inward current responses in the GABAergic neurons were
      highly sensitive to a selective antagonist for alpha3beta2- and alpha6beta2
      containing receptors, alpha-conotoxin MII (alphaCtxMII). A subset of these
      neurons exhibited a faster alpha-bungarotoxin-sensitive inward current component,
      indicating the expression of alpha7-containing nAChRs. We also found that the
      activation of presynaptic nAChRs induced release of GABA, which elicited a burst
      of miniature inhibitory postsynaptic currents mediated by GABA(A) receptors in
      non-GABAergic neurons. This ACh-induced GABA release was mediated mainly by
      alphaCtxMII-sensitive nAChRs and resulted from the activation of voltage
      dependent calcium channels. Morphological analysis revealed that recorded GFP
      positive neurons are interneurons and GFP-negative neurons include projection
      neurons. These findings suggest that nAChRs are involved in the regulation of
      GABAergic inhibition and modulate visual processing in the sSC.

PMID- 16107533
TI  - Role of AMPA receptor desensitization and the side effects of a DMSO vehicle on
      reticulospinal EPSPs and locomotor activity.
AB  - Activation of the vertebrate locomotor network is mediated by glutamatergic
      synaptic drive, normally initiated by the brain stem. Previous investigations
      have studied the role of glutamate receptors, especially NMDA receptors, in
      generating and regulating locomotor pattern generation. Few studies, however,
      have focused on the role of AMPA receptors in shaping network activity,
      especially with regard to their rapid desensitization. It is important to
      determine whether AMPA receptor desensitization plays a role in regulating
      neuronal network activity. We examined this question on both the network and
      synaptic levels in the lamprey (Lampetra fluviatilis) spinal cord using a
      selective and potent inhibitor of AMPA receptor desensitization, cyclothiazide
      (CTZ). The solvent dimethyl sulfoxide (DMSO) is commonly used to dissolve this
      drug, as well as many others. Unexpectedly, the vehicle alone already at 0.02%,
      but not at 0.01%, caused significant increases in excitatory postsynaptic
      potential (EPSP) amplitudes and NMDA-induced locomotor frequency. The results
      indicate that DMSO may have a profound influence when used > or = 0.02%, a
      concentration 10-50 times less than that most commonly used. Subsequently we
      applied CTZ concentrations < or =10 microM (DMSO < or =0.01%). CTZ (1.25-5
      microM) caused an appreciable and significant increase in EPSPs mediated by non
      NMDA receptors and in both AMPA- and NMDA-induced locomotor frequency, but no
      effects on EPSPs mediated by NMDA receptors. From the effects of CTZ it is
      apparent that AMPA receptor desensitization plays an important role in
      determining locomotor frequency and that this is likely a result of its limiting
      function on AMPA receptor-mediated EPSPs.

PMID- 16107534
TI  - Ca2+-activated K+-current density is correlated with soma size in rat vestibular
      afferent neurons in culture.
AB  - Vestibular-afferent neurons (VANs) transmit information about linear and angular
      accelerations during head movements from vestibular end organs to vestibular
      nuclei. In situ, these neurons show heterogeneous discharge patterns that may be
      produced by differences in their intrinsic properties. However, little is known
      about the ionic currents underlying their different firing patterns. Using the
      whole cell patch-clamp technique, we analyzed the expression of Ca(2+) and Ca(2+)
      activated K(+) currents (I(KCa)) in primary cultured neurons isolated from young
      rats (p7-p10). We found two overlapping subpopulations of VANs classified
      according to low-threshold Ca(2+)-current [low-voltage-activated (LVA)]
      expression; LVA (-) neurons, formed by small cells, and LVA (+) neurons composed
      of medium to large cells. The I(KCa) in both cell-groups was carried through
      channels of high (BK), intermediate (IK), and low conductance (SK), besides a
      resistant channel to classical blockers (IR). BK was expressed preferentially in
      LVA (+) cells, whereas IR expression was preferentially in LVA (-) cells. No
      correlation between SK and IK expression with the soma size was found. Current
      clamp experiments showed that BK participates in the adaptation of discharge and
      in the duration of the action potential, whereas SK and IK did not show a
      significant contribution to electrical discharge of cultured VANs. However,
      because of the low number of VANs in culture with repetitive firing it is
      difficult to interpret our results in terms of discharge patterns. Our results
      demonstrate that vestibular-afferent neurons possess different Ca(2+)-activated
      K(+) (K(Ca)) channels and that their expression, heterogeneous among the cells,
      would contribute to explain some of the differences in the electrical-firing
      properties of these neurons.

PMID- 16107535
TI  - Dietary soy isoflavone induced increases in antioxidant and eNOS gene expression
      lead to improved endothelial function and reduced blood pressure in vivo.
AB  - Epidemiological evidence suggests that populations consuming large amounts of soy
      protein have a reduced incidence of coronary heart disease (1-5). The
      cardiovascular risks associated with conventional hormone replacement therapy in
      postmenopausal women (5-7) have precipitated a search for alternative estrogen
      receptor modulators. Here we report that long-term feeding of rats with a soy
      protein-rich (SP) diet during gestation and adult life results in decreased
      oxidative stress, improved endothelial function, and reduced blood pressure in
      vivo measured by radiotelemetry in aged male offspring. Improved vascular
      reactivity in animals fed an SP diet was paralleled by increased mitochondrial
      glutathione and mRNA levels for endothelial nitric oxide synthase (eNOS) and the
      antioxidant enzymes manganese superoxide dismutase and cytochrome c oxidase.
      Reduced eNOS and antioxidant gene expression, impaired endothelial function, and
      elevated blood pressure in animals fed a soy-deficient diet was reversed after
      refeeding them an SP diet for 6 months. Our findings suggest that an SP diet
      increases eNOS and antioxidant gene expression in the vasculature and other
      tissues, resulting in reduced oxidative stress and increased NO bioavailability.
      The improvement in endothelial function, increased gene expression, and reduced
      blood pressure by soy isoflavones have implications for alternative therapy for
      postmenopausal women and patients at risk of coronary heart disease.

PMID- 16107536
TI  - Reconstruction of 3D stacked-up structures by rat small hepatocytes on
      microporous membranes.
AB  - The three-dimensional (3D) culture of hepatocytes is essential for the
      reconstruction of functional hepatic tissues in vitro. In the present experiment,
      we developed a 3D-culture method in order to reconstruct hepatic cordlike
      structures by stacking up two-dimensional (2D) tissues composed of rat small
      hepatocytes (SHs), which are hepatic progenitor cells. Pairs of membranes were
      prepared and the cells were separately cultured on each membrane. After the SH
      colonies had developed, one membrane was inverted on top of the other to form an
      SH bilayer. Thereafter, we investigated whether the stacked cells were organized
      into differentiated tissues. In the 3D stacked-up structures, bile canaliculi
      (BC) started to form and gradually developed into anastomosing networks.
      Transmission electron microscopy revealed that the SHs of the upper and lower
      layers adhered to one another, and that BC formed between them. Bile canalicular
      proteins localized on the lumina of the tubular structures. Furthermore, the
      cells within the structures exhibited mRNA transcription of the hepatic
      differentiation markers and maintained a relatively high level of albumin
      secretion. We conclude that highly differentiated 3D tissues, including
      functional BC, can be reconstructed by stacking up layers of SHs. This 3D stacked
      up culture is useful for the reconstruction of tissue-engineered livers.

PMID- 16107537
TI  - Direct regulation of intestinal fate by Notch.
AB  - The signals that maintain the proper balance between adult intestinal cell types
      are poorly understood. Loss-of-function studies have implicated the Notch pathway
      in the regulation of intestinal fate during development. However, it is unknown
      whether Notch has a role in maintaining the balance of different cell types in
      the adult intestine and whether it acts reversibly. To determine whether Notch
      has a direct effect on intestinal development and adult intestinal cell turnover,
      we have used a gain-of-function approach to activate Notch. Ectopic Notch
      signaling in adult intestinal progenitor cells leads to a bias against secretory
      fates, whereas ectopic Notch activation in the embryonic foregut results in
      reversible defects in villus morphogenesis and loss of the proliferative
      progenitor compartment. We conclude that Notch regulates adult intestinal
      development by controlling the balance between secretory and absorptive cell
      types. In the embryo, Notch activation perturbs morphogenesis, possibly through
      effects on stem or progenitor cells.

PMID- 16107538
TI  - Generation of phytate-free seeds in Arabidopsis through disruption of inositol
      polyphosphate kinases.
AB  - Phytate (inositol hexakisphosphate, IP6) is a regulator of intracellular
      signaling, a highly abundant animal antinutrient, and a phosphate store in plant
      seeds. Here, we report a requirement for inositol polyphosphate kinases, AtIPK1
      and AtIPK2beta, for the later steps of phytate synthesis in Arabidopsis thaliana.
      Coincident disruption of these kinases nearly ablates seed phytate without
      accumulation of phytate precursors, increases seed-free phosphate by 10-fold, and
      has normal seed yield. Additionally, we find a requirement for inositol
      tetrakisphosphate (IP4)/inositol pentakisphosphate (IP5) 2-kinase activity in
      phosphate sensing and root hair elongation. Our results define a commercially
      viable strategy for the genetic engineering of phytate-free grain and provide
      insights into the role of inositol polyphosphate kinases in phosphate signaling
      biology.

PMID- 16107539
TI  - Real-time imaging of type III secretion: Salmonella SipA injection into host
      cells.
AB  - Many pathogenic and symbiotic Gram-negative bacteria employ type III secretion
      systems to inject "effector" proteins into eukaryotic host cells. These effectors
      manipulate signaling pathways to initiate symbiosis or disease. By using time
      lapse microscopy, we have imaged delivery of the Salmonella type III effector
      protein SipA/SspA into animal cells in real time. SipA delivery mostly began 10
      90 sec after docking and proceeded for 100-600 sec until the bacterial SipA pool
      (6 +/- 3 x 10(3) molecules) was exhausted. Similar observations were made for the
      effector protein SopE. This visualization of type III secretion in real time
      explains the efficiency of host cell manipulation by means of this virulence
      system.

PMID- 16107540
TI  - Distinct basal ganglia territories are engaged in early and advanced motor
      sequence learning.
AB  - In this study, we used functional MRI (fMRI) at high field (3T) to track the time
      course of activation in the entire basal ganglia circuitry, as well as other
      motor-related structures, during the explicit learning of a sequence of finger
      movements over a month of training. Fourteen right-handed healthy volunteers had
      to practice 15 min daily a sequence of eight moves using the left hand. MRI
      sessions were performed on days 1, 14 and 28. In both putamen, activation
      decreased with practice in rostrodorsal (associative) regions. In contrast, there
      was a significant signal increase in more caudoventral (sensorimotor) regions of
      the putamen. Subsequent correlation analyses between signal variations and
      behavioral variables showed that the error rate (movement accuracy) was
      positively correlated with signal changes in areas activated during early
      learning, whereas reaction time (movement speed) was negatively correlated with
      signal changes in areas activated during advanced learning stages, including the
      sensorimotor putamen and globus pallidus. These results suggest the possibility
      that motor representations shift from the associative to the sensorimotor
      territories of the striato-pallidal complex during the explicit learning of motor
      sequences, suggesting that motor skills are stored in the sensorimotor territory
      of the basal ganglia that supports a speedy performance.

PMID- 16107541
TI  - Conformable, flexible, large-area networks of pressure and thermal sensors with
      organic transistor active matrixes.
AB  - Skin-like sensitivity, or the capability to recognize tactile information, will
      be an essential feature of future generations of robots, enabling them to operate
      in unstructured environments. Recently developed large-area pressure sensors made
      with organic transistors have been proposed for electronic artificial skin (E
      skin) applications. These sensors are bendable down to a 2-mm radius, a size that
      is sufficiently small for the fabrication of human-sized robot fingers. Natural
      human skin, however, is far more complex than the transistor-based imitations
      demonstrated so far. It performs other functions, including thermal sensing.
      Furthermore, without conformability, the application of E-skin on three
      dimensional surfaces is impossible. In this work, we have successfully developed
      conformable, flexible, large-area networks of thermal and pressure sensors based
      on an organic semiconductor. A plastic film with organic transistor-based
      electronic circuits is processed to form a net-shaped structure, which allows the
      E-skin films to be extended by 25%. The net-shaped pressure sensor matrix was
      attached to the surface of an egg, and pressure images were successfully obtained
      in this configuration. Then, a similar network of thermal sensors was developed
      with organic semiconductors. Next, the possible implementation of both pressure
      and thermal sensors on the surfaces is presented, and, by means of laminated
      sensor networks, the distributions of pressure and temperature are simultaneously
      obtained.

PMID- 16107542
TI  - Structure of a bacterial BLUF photoreceptor: insights into blue light-mediated
      signal transduction.
AB  - Light is an essential environmental factor, and many species have evolved the
      capability to respond to it. Blue light is perceived through three flavin
      containing photoreceptor families: cryptochromes, light-oxygen-voltage, and BLUF
      (sensor of blue light using flavin adenine dinucleotide, FAD) domain proteins.
      BLUF domains are present in various proteins from Bacteria and lower Eukarya.
      They are fully modular and can relay signals to structurally and functionally
      diverse output units, most of which are implicated in nucleotide metabolism. We
      present the high resolution crystal structure of the dark resting state of BlrB,
      a short BLUF domain-containing protein from Rhodobacter sphaeroides. The
      structure reveals a previously uncharacterized FAD-binding fold. Along with other
      lines of evidence, it suggests mechanistic aspects for the photocycle that is
      characterized by a red-shifted absorbance of the flavin. The isoalloxazine ring
      of FAD binds in a cleft between two helices, whereas the adenine ring points into
      the solvent. We propose that the adenine ring serves as a hook mediating the
      interaction with its effector/output domain. The structure suggests a unique
      photochemical signaling switch in which the absorption of light induces a
      structural change in the rim surrounding the hook, thereby changing the protein
      interface between BLUF and the output domain.

PMID- 16107543
TI  - Neural mechanism in anterior prefrontal cortex for inhibition of prolonged set
      interference.
AB  - Once one cognitive set dominates our behavior, it continues to influence
      subsequent behavior for a while even after a task to be performed is changed to
      another. Despite abundant knowledge of the inhibitory mechanisms that are
      recruited at the first trial after the change (the first inhibition trial),
      little is known about the inhibition of prolonged proactive interference from a
      previous set that lingers for several trials after the first inhibition trial.
      The present functional MRI study explored the neural mechanisms for inhibition of
      a previous set that were recruited after the first inhibition trial. A modified
      Wisconsin Card Sorting Test was used where "dual-match stimuli" were
      intermittently presented and allowed subjects to perform correctly based on
      previously appropriate, now inappropriate, responses. In response to the dual
      match stimulus at "release" trials presented after the first inhibition trials,
      the subjects were transiently exempted from inhibiting the prolonged previous
      set. As expected from the exempted inhibitory demands, significant reaction time
      decrease was revealed in the release trials. Consistent with the behavioral
      results, transient signal decrease time-locked to the release trials was revealed
      in the left anterior part of the superior frontal sulcus. Moreover, the anterior
      prefrontal region was not sensitive to the task change, which exhibited a marked
      contrast to the left posterior inferior prefrontal region that showed significant
      signal changes in both events. These results revealed multiple inhibitory
      mechanisms in the lateral prefrontal cortex that are recruited in different
      temporal contexts of the interference from a previous cognitive set.

PMID- 16107544
TI  - Assessing health-related quality of life in children with recurrent headache:
      reliability and validity of the PedsQLTM 4.0 in a pediatric headache sample.
AB  - OBJECTIVE: To evaluate the reliability and validity of a commonly used measure of
      health-related quality of life (HRQOL), the Pediatric Quality of Life Inventory
      (PedsQL 4.0), in a sample of children with a recurrent headache syndrome.
      METHODS: Participants were 40 children aged 7-12 who completed measures of HRQOL,
      headache-related disability, and headache activity during a baseline period and
      following a self-directed cognitive-behavioral intervention. RESULTS: The data
      are supportive of the reliability (internal consistency and test-retest) and
      validity (criterion related, convergent, known-groups, and responsiveness to
      intervention) of the PedsQL 4.0 within a pediatric headache sample. CONCLUSIONS:
      We conclude that the PedsQL 4.0 is a reliable and valid measure of HRQOL in
      children with recurrent headache and captures important information not routinely
      evaluated in chronic pain populations.

PMID- 16107546
TI  - Photomutagenicity of retinyl palmitate by ultraviolet a irradiation in mouse
      lymphoma cells.
AB  - Retinyl palmitate (RP), a storage form of vitamin A, is frequently used as a
      cosmetic ingredient, with more than 700 RP-containing cosmetic products on the
      U.S. market in 2004. There are concerns for the possible genotoxicity and
      carcinogenicity of RP when it is exposed to sunlight. To evaluate the
      photomutagenicity of RP in cells when exposed to ultraviolet A (UVA) light,
      L5178Y/Tk+/- mouse lymphoma cells were treated with different doses of RP
      alone/or in the presence of UVA light. Treatment of the cells with RP alone at
      the dose range of 25-100 microg/ml did not increase mutant frequencies (MFs) over
      the negative control, whereas treatment of cells with 1-25 microg/ml RP under UVA
      light (82.8 mJ/cm2/min for 30 min) produced a dose-dependent mutation induction.
      The mean induced MF (392 x 10(-6)) for treatment with 25 microg/ml RP under UVA
      exposure was about threefold higher than that for UVA alone (122 x 10(-6)), a
      synergistic effect. To elucidate the underlying mechanism of action, we examined
      the mutants for loss of heterozygosity (LOH) at four microsatellite loci spanning
      the entire chromosome 11, on which the Tk gene is located. The mutational
      spectrum for the RP + UVA treatment was significantly different from the negative
      control, but not significantly different from UVA exposure alone. Ninety four
      percent of the mutants from RP + UVA treatment lost the Tk+ allele, and 91% of
      the deleted sequences extended more than 6 cM in chromosome length, indicating
      clastogenic events affecting a large segment of the chromosome. These results
      suggest that RP is photomutagenic in combination with UVA exposure in mouse
      lymphoma cells, with a clastogenic mode-of-action.

PMID- 16107547
TI  - Lipids versus proteins as major targets of pro-oxidant, direct-acting hemolytic
      agents.
AB  - Lipid peroxidation and the accompanying translocation of phosphatidylserine (PS)
      from the inner to the outer leaflet of the lipid bilayer have recently been
      identified as key components of a signaling pathway for phagocytosis of apoptotic
      cells by macrophages. Drug-induced hemolytic anemia has long been known to be
      caused by an accelerated uptake of damaged (but intact) erythrocytes by
      macrophages in the spleen, and this process has been associated with enhanced
      formation of reactive oxygen species (ROS). However, the role of lipid
      peroxidation in hemolytic injury has remained unclear, and the effect of
      hemolytic agents on the distribution of PS in the erythrocyte membrane is
      unknown. The present studies were undertaken to determine whether lipid
      peroxidation and PS translocation could be detected in rat and human erythrocytes
      by three types of direct-acting hemolytic agents--dapsone hydroxylamine, divicine
      hydroquinone, and phenylhydrazine. 2',7'-Dichlorodihydrofluorescein diacetate was
      employed as a probe for intracellular ROS formation; lipid peroxidation was
      assessed by GC/MS analysis of F2-isoprostanes; and PS externalization was
      measured by annexin V labeling and the prothrombinase assay. The data confirmed
      that all three hemolytic agents generate ROS within erythrocytes under hemolytic
      conditions; however, no evidence for lipid peroxidation or PS translocation was
      detected. Instead, ROS production by these hemolytic agents was associated with
      extensive binding of oxidized and denatured hemoglobin to the membrane
      cytoskeleton. The data suggest that the transmembrane signal for macrophage
      recognition of hemolytic injury may be derived from oxidative alterations to
      erythrocyte proteins rather than to membrane lipids.

PMID- 16107548
TI  - Polybrominated diphenyl ether (PBDE) effects in rat neuronal cultures: 14C-PBDE
      accumulation, biological effects, and structure-activity relationships.
AB  - Polybrominated diphenyl ethers (PBDEs), widely used as flame-retardants, are now
      recognized as globally distributed pollutants, and are detected in most
      environmental and biological samples, including human blood, adipose tissue, and
      breast milk. Due to their wide use in commercial products and their persistent
      nature, long-term exposure to PBDEs may pose a human health risk, especially to
      children. Our previous reports showed that the commercial PBDE mixture, DE-71,
      affected protein kinase C (PKC) and calcium homeostasis in a similar way to those
      of a structurally-related polychlorinated biphenyl (PCB) mixture. These
      intracellular signaling events are associated with neuronal development and
      learning and memory function. The objectives of the present study were to test
      whether environmentally relevant PBDE congeners, with different position and
      number of bromines, affected PKC translocation in cerebellar granule neuronal
      cultures and compare the potency and efficacy of PBDE congeners with their 14C
      accumulation. All the tested PBDE congeners increased 3H-phorbol ester (PDBu)
      binding, and a significant effect was seen as low as 10 microM. Among the
      congeners tested, 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47) increased 3H-PDBu
      binding in a concentration-dependent manner and to a greater extent than other
      congeners. These effects were seen at concentrations and exposure times where no
      cytotoxicity was observed. The efficacy of PBDE congeners varied with their
      structural composition, and the effects seen on 3H-PDBu binding with some PBDE
      congeners are similar to those of PCB congeners. Cerebellar granule neurons
      accumulated all three PBDE congeners (PBDEs 47, 99, and 153) following exposure.
      At the lowest concentration (0.67 microM), about 13-18% of the total dose of 14C
      PBDE congeners was accumulated by these neurons. There were distinct differences
      in the pattern of 14C-PBDE accumulation among the PBDE congeners. The 14C-PBDE
      accumulation, either represented as percent basis or nanomole basis, was much
      lower for the 30.69 microM PBDE 99 and 10.69-30.69 microM PBDE 153 than at the
      lower concentrations, which may be due to low solubility of these congeners. The
      accumulation pattern with PBDE 47 did not vary with concentration. On a nanomole
      accumulation basis, PBDEs 47, 99, and 153 accumulation was linear with time.
      While the nanomole accumulation was linear with concentration for PBDE 47, it is
      nonlinear for PBDEs 99 and 153. The pattern of PBDE accumulation seems to
      correlate with the effects on PKC translocation, with regression values of 0.773
      0.991. These results indicate that PBDEs affected PKC translocation in neurons in
      a similar way to those of other organohalogens, some PBDE congeners are equally
      efficacious as the respective PCB congeners, and PBDE accumulation correlated
      well with PKC translocation, suggesting a common mode of action for this group of
      chemicals.

PMID- 16107549
TI  - Differential expression of CYP1A, 2B, and 3A genes in the F344 rat following
      exposure to a polybrominated diphenyl ether mixture or individual components.
AB  - Polybrominated diphenyl ethers (PBDEs), used as flame retardants, have been
      detected in the environment and in mammalian tissues and fluids. Evidence
      indicates that PBDE mixtures induce CYPs through aryl hydrocarbon receptor (AhR)
      dependent and -independent pathways. The present work has investigated the
      effects of individual components of a commercial PBDE mixture (DE71) on
      expression of CYP1A1, a biomarker for activation of the AhR (dioxin-like), and
      CYP2B and CYP3A, biomarkers for activation of the constitutive androstane and
      pregnanexreceptors (CAR and PXR), respectively, in the rat. Male F344 rats were
      dosed orally on three consecutive days with either DE71, PBDE components,
      2,2',4,4'-tetraBDE (BDE47), 2,2',4,4',5-pentaBDE (BDE99), 2,2',4,4',5,5'-hexaBDE
      (BDE153), representative polybrominated dibenzofurans (PBDFs) present in DE71, or
      reference PCBs. Differential expression of target genes was determined in liver
      24 h after the last dose. Quantitative PCR analysis indicated up-regulation of
      CYP1A1 by DE71; however, the response was weak compared to that for dioxin-like
      PCB126. Individual PBDE components of DE71 up-regulated CYP1A1 only at the
      highest administered dose (100 micromol/kg/day). Representative PBDFs efficiently
      up-regulated CYP1A1; therefore, they, along with other PBDFs and polybrominated
      dibenzodioxins detected in DE71 and individual PBDE components, may be
      responsible for most, if not all, dioxin-like properties previously observed for
      PBDEs. Conversely, PBDEs appear capable of up-regulating CYP2B and CYP3A in rats
      at doses similar to that for non-dioxin-like PCB153. These results indicate that
      in vivo PBDE-mediated toxicity would be better categorized by AhR-independent
      mechanisms, rather than the well-characterized AhR-dependent mechanism associated
      with exposure to dioxin-like chemicals.

PMID- 16107550
TI  - Effects of 2,4-D and DCP on the DHT-induced androgenic action in human prostate
      cancer cells.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D) and its metabolite 2,4-dichlorophenol
      (DCP) are used extensively in agriculture as herbicides, and are suspected of
      potential endocrine disruptor activity. In a previous study, we showed that these
      compounds exhibited synergistic androgenic effects by co-treatment with
      testosterone in the Hershberger assay. To elucidate the mechanisms of the
      synergistic effects of these compounds on the androgenicity of testosterone, the
      androgenic action of 2,4-D and DCP was characterized using a mammalian detection
      system in prostate cancer cell lines. In in vitro assay systems, while 2,4-D or
      DCP alone did not show androgenic activity, 2,4-D or DCP with 5alpha
      dihydroxytestosterone (DHT) exhibited synergistic androgenic activities. Co
      treatment of 10 nM 2,4-D or DCP with 10 nM DHT was shown to stimulate the cell
      proliferation by 1.6-fold, compared to 10 nM DHT alone. In addition, in transient
      transfection assays, androgen-induced transactivation was also increased to a
      maximum of 32-fold or 1.28-fold by co-treatment of 2,4-D or DCP with DHT,
      respectively. However, 2,4-D and DCP exerted no effects on either mRNA or protein
      levels of AR. In a competitive AR binding assay, 2,4-D and DCP inhibited androgen
      binding to AR, up to 50% at concentrations of approximately 0.5 microM for both
      compounds. The nuclear translocation of green fluorescent protein-AR fusion
      protein in the presence of DHT was promoted as the result of the addition of 2,4
      D and DCP. Collectively, these results that 2,4-D and DCP enhanced DHT-induced AR
      transcriptional activity might be attributable, at least in part, to the
      promotion of AR nuclear translocation.

PMID- 16107551
TI  - Brief postnatal PBDE exposure alters learning and the cholinergic modulation of
      attention in rats.
AB  - Polybrominated diphenyl ethers (PBDEs), chemicals commonly used as flame
      retardants, are ubiquitous in the environment and bioaccumulate in humans and
      wildlife. However, little is known about their potential toxicological
      properties. In the present study, male Long-Evans rats orally administered the
      commercial PBDE mixture DE-71 or corn oil for 1 week, beginning at postnatal day
      (PND) 6, were tested on a visual discrimination task and two sustained attention
      tasks. After completion of these tasks, the rats were administered a drug
      challenge with the muscarinic antagonist scopolamine (0, 0.01, 0.03, 0.05 mg/kg),
      which was injected subcutaneously 30 min prior to testing on the second sustained
      attention task. The DE-71-exposed rats demonstrated deficits in learning but not
      in sustained attention when compared to controls. Scopolamine impaired the
      animals' ability to detect the brief visual cues in controls, as evidenced by
      decreases in accuracy and increases in omission errors. However, the DE-71
      exposed rats were subsensitive to the effects of scopolamine on omission errors,
      particularly on trials in which a long delay preceded the cue, suggesting
      alterations in the cholinergic modulation of sustained attention. For the DE-71
      exposed rats, the lack of sustained attention deficits in the absence of the
      drug, coupled with the subsensitivity to scopolamine's effects on sustained
      attention, suggest that although this PBDE mixture produced lasting alterations
      in cholinergic functioning, either (1) these alterations were not of sufficient
      magnitude to be behaviorally relevant, or (2) behavioral deficits resulting from
      these alterations were overcome by the development of compensatory neural
      mechanisms or response strategies in adulthood.

PMID- 16107552
TI  - Endothelin-1-mediated increase in reactive oxygen species and NADPH Oxidase
      activity in hearts of aryl hydrocarbon receptor (AhR) null mice.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      characterized to play a role in detection and adaptation to environmental
      stimuli. Genetic deletion of the AhR results in cardiac hypertrophy that is
      mediated primarily by endothelin-1 (ET-1); ET-1 has been implicated in the
      elevation of reactive oxygen species (ROS) in the heart, which are thought to
      contribute to several cardiovascular disorders, including cardiac hypertrophy.
      Thus, we tested the novel hypothesis that ET-1 induces ROS in AhR null mice via
      ET(A) receptor activation. We first confirmed the presence of ROS in the hearts
      of AhR null mice by measuring superoxide (O2*-)-dependent oxidation of
      dihydroethidium. Ethidium fluorescence was increased 10-fold in the hearts of AhR
      null mice, compared to the wild type. Then, to elucidate whether ET-1 mediated
      the increase in ROS, mice were chronically treated with 100 ng/kg/day of the
      ET(A) receptor antagonist BQ-123. In AhR null mice, BQ-123 significantly reduced
      elevated plasma 8-isoprostane, a systemic end product of phospholipid oxidation
      by ROS, and cardiac thiobarbituric acid reactive substances (TBARS), a
      nonspecific assessment of ROS production. Furthermore, BQ-123 reduced both
      cardiac lucigenin chemiluminescence and cardiac mRNA expression of NAD(P)H
      oxidase subunits gp91phox, p47phox, and p67phox in AhR null mice below the levels
      observed in wild-type mice. These findings demonstrate that ET-1 activation of
      ET(A) receptors mediates an increase in ROS that is associated with cardiac
      hypertrophy in AhR null mice. In addition, the ET-1-mediated increase in ROS
      appears to be initiated via increased NAD(P)H oxidase activity.

PMID- 16107553
TI  - Effect of diesel exhaust particles on allergic reactions and airway
      responsiveness in ovalbumin-sensitized brown Norway rats.
AB  - We have previously demonstrated that exposure to diesel exhaust particles (DEP)
      prior to ovalbumin (OVA) sensitization in rats reduced OVA-induced airway
      inflammation. In the present study, Brown Norway rats were first sensitized to
      OVA (42.3 +/- 5.7 mg/m3) for 30 min on days 1, 8, and 15, then exposed to
      filtered air or DEP (22.7 +/- 2.5 mg/m3) for 4 h/day on days 24-28, and
      challenged with OVA on day 29. Airway responsiveness was examined on day 30, and
      animals were sacrificed on day 31. Ovalbumin sensitization and challenge resulted
      in a significant infiltration of neutrophils, lymphocytes, and eosinophils into
      the lung, elevated presence of CD4+ and CD8+ T lymphocytes in lung draining lymph
      nodes, and increased production of serum OVA-specific immunoglobulin (Ig)E and
      IgG. Diesel exhaust particles pre-exposure augmented OVA-induced production of
      allergen-specific IgE and IgG and pulmonary inflammation characterized by marked
      increases in T lymphocytes and infiltration of eosinophils after OVA challenge,
      whereas DEP alone did not have these effects. Although OVA-sensitized rats showed
      modest response to methacholine challenge, it was the combined DEP and OVA
      exposure that produced significant airway hyperresponsiveness in this animal
      model. The effect of DEP pre-exposure on OVA-induced immune responses correlated
      with an interactive effect of DEP with OVA on increased production of reactive
      oxygen species (ROS) and nitric oxide (NO) by alveolar macrophages (AM) and
      alveolar type II (ATII) cells, NO levels in bronchoalveolar lavage fluid, the
      induction of inducible NO synthase expression in AM and ATII cells, and a
      depletion of total intracellular glutathione (GSH) in AM and lymphocytes. These
      results show that DEP pre-exposure exacerbates the allergic responses to the
      subsequent challenge with OVA in OVA-sensitized rats. This DEP effect may be, at
      least partially, attributed to the elevated generation of ROS in AM and ATII
      cells, a depletion of GSH in AM and lymphocytes, and an increase in AM and ATII
      cell production of NO.

PMID- 16107554
TI  - Sustained effect of inhaled diesel exhaust particles on T-lymphocyte-mediated
      immune responses against Listeria monocytogenes.
AB  - Studies have shown that exposure to diesel exhaust particles (DEP) suppresses
      pulmonary host defense against bacterial infection. The present study was carried
      out to characterize whether DEP exposure exerts a sustained effect in which
      inhaled DEP increase the susceptibility of the lung to bacterial infection
      occurring at a later time. Brown Norway rats were exposed to filtered air or DEP
      by inhalation at a dose of 21.2 +/- 2.3 mg/m3, 4 h/day for 5 days, and
      intratracheally instilled with saline or 100,000 Listeria monocytogenes
      (Listeria) 7 days after the final DEP exposure. Bacterial growth and cellular
      responses to DEP and Listeria exposures were examined at 3 and 7 days post
      infection. The results showed that inhaled DEP prolonged the growth of bacteria,
      administered 7 days post DEP exposure, in the lung as compared to the air-exposed
      controls. Pulmonary responses to Listeria infection were characterized by
      increased production of interleukin (IL)-1beta, tumor necrosis factor (TNF)
      alpha, IL-12, and IL-10 by alveolar macrophages (AM) and increased presence of T
      lymphocytes and their CD4+ and CD8+ subsets in lung draining lymph nodes that
      secreted elevated levels of IL-2, IL-6, IL-10, and interferon (IFN)-gamma. Diesel
      exhaust particles were found to inhibit Listeria-induced production of IL-1beta
      and TNF-alpha, which are responsible for the innate immunity, and IL-12, which
      initiates the development of T helper (Th)1 responses, but enhance Listeria
      induced AM production of IL-10, which prolongs Listeria survival in these
      phagocytes. The dual action of DEP on AM production of IL-12 and IL-10 correlated
      with an inhibition of the development of bacteria-specific T lymphocytes by DEP.
      Cytokine production by lymphocytes from DEP- and Listeria-exposed rats showed a
      marked decrease in the production of IL-2, IL-10, and IFN-gamma compared to
      Listeria infection alone, suggesting either that DEP inhibit the production of
      cytokines by lymphocytes or that these lymphocytes contained T-cell subsets that
      are different from those of Listeria infection alone and less effective in
      mediating Th1 immune responses. This study demonstrates that inhaled DEP, after a
      7-day resting period, increase the susceptibility of the lung to bacterial
      infection occurring at a later time by inhibiting macrophage immune function and
      suppressing the development of T-cell-mediated immune responses. The results
      support the epidemiological observations that exposure to DEP may be responsible
      for the pulmonary health effects on humans.

PMID- 16107555
TI  - In silico methods for evaluating human allergenicity to novel proteins:
      International Bioinformatics Workshop Meeting Report, 23-24 February 2005.
AB  - The ILSI Health and Environmental Sciences Institute (HESI) hosted an expert
      workshop 22-24 February 2005 in Mallorca, Spain, to review the state-of-the
      science for conducting a sequence homology/bioinformatics evaluation in the
      context of a comprehensive allergenicity assessment for novel proteins, to obtain
      consensus on the value and role of bioinformatics in evaluating novel proteins,
      and to discuss the utility and methods of allergen-specific IgE testing in the
      diagnosis of food allergy. The workshop participants included over forty
      international experts from academia, industry, and government. The workshop was
      hosted by the HESI Protein Allergenicity Technical committee, which has
      established a long-term program whose mission is to advance the scientific
      understanding of the relevant parameters for characterizing the allergenic
      potential of novel proteins.

PMID- 16107556
TI  - Oxidative stress-induced apoptosis in neurons correlates with mitochondrial DNA
      base excision repair pathway imbalance.
AB  - Neurodegeneration can occur as a result of endogenous oxidative stress. Primary
      cerebellar granule cells were used in this study to determine if mitochondrial
      DNA (mtDNA) repair deficiencies correlate with oxidative stress-induced apoptosis
      in neuronal cells. Granule cells exhibited a significantly higher intracellular
      oxidative state compared with primary astrocytes as well as increases in
      reductants, such as glutathione, and redox sensitive signaling molecules, such as
      AP endonuclease/redox effector factor-1. Cerebellar granule cultures also
      exhibited an increased susceptibility to exogenous oxidative stress. Menadione
      (50 muM) produced twice as many lesions in granule cell mtDNA compared with
      astrocytes, and granule cell mtDNA repair was significantly less efficient. A
      decreased capacity to repair oxidative mtDNA damage correlates strongly with
      mitochondrial initiated apoptosis in these neuronal cultures. Interestingly, the
      mitochondrial activities of initiators for base excision repair (BER), the
      bifunctional glycosylase/AP lyases as well as AP endonuclease, were significantly
      higher in cerebellar granule cells compared with astrocytes. The increased
      mitochondrial AP endonuclease activity in combination with decreased polymerase
      gamma activity may cause an imbalance in oxidative BER leading to an increased
      production and persistence of mtDNA damage in neurons when treated with
      menadione. This study provides evidence linking neuronal mtDNA repair capacity
      with oxidative stress-related neurodegeneration.

PMID- 16107557
TI  - Distant sequences determine 5' end formation of cox3 transcripts in Arabidopsis
      thaliana ecotype C24.
AB  - The genomic environments and the transcripts of the mitochondrial cox3 gene are
      investigated in three Arabidopsis thaliana ecotypes. While the proximate 5'
      sequences up to nucleotide position -584, the coding regions and the 3' flanking
      regions are identical in Columbia (Col), C24 and Landsberg erecta (Ler), genomic
      variation is detected in regions further upstream. In the mitochondrial DNA of
      Col, a 1790 bp fragment flanked by a nonanucleotide direct repeat is present
      beyond position -584 with respect to the ATG. While in Ler only part of this
      insertion is conserved, this sequence is completely absent in C24, except for a
      single copy of the nonanucleotide direct repeat. Northern hybridization reveals
      identical major transcripts in the three ecotypes, but identifies an additional
      abundant 60 nt larger mRNA species in C24. The extremities of the most abundant
      mRNA species are identical in the three ecotypes. In C24, an extra major 5' end
      is abundant. This terminus and the other major 5' ends are located in identical
      sequence regions. Inspection of Atcox3 transcripts in C24/Col hybrids revealed a
      female inheritance of the mRNA species with the extra 5' terminus. Thus, a
      mitochondrially encoded factor determines the generation of an extra 5' mRNA end.

PMID- 16107558
TI  - A role for Jsn1p in recruiting the Arp2/3 complex to mitochondria in budding
      yeast.
AB  - Although the Arp2/3 complex localizes to the leading edge of motile cells,
      endocytic structures, and mitochondria in budding yeast, the mechanism for
      targeting the Arp2/3 complex to different regions in the cell is not well
      understood. We find that Jsn1p, a member of the PUF family of proteins,
      facilitates association of Arp2/3 complex to yeast mitochondria. Jsn1p localizes
      to punctate structures that align along mitochondria, cofractionates with a
      mitochondrial marker protein during subcellular fractionation, and is both
      protease sensitive and carbonate extractable in isolated mitochondria. Thus,
      Jsn1p is a peripheral membrane protein that is associated with the outer leaflet
      of the mitochondrial outer membrane. Jsn1p colocalized and coimmunoprecipitated
      with mitochondria-associated Arc18p-GFP, and purified Arp2/3 complex bound to
      isolated TAP-tagged Jsn1p. Moreover, deletion of JSN1 reduces the amount of
      Arc18p-GFP that colocalizes and is recovered with mitochondria twofold, and
      jsn1Delta cells exhibited defects in mitochondrial morphology and motility
      similar to those observed in Arp2/3 complex mutants. Thus, Jsn1p has physical
      interactions with mitochondria-associated Arp2/3 complex and contributes to
      physical and functional association of the Arp2/3 complex with mitochondria.

PMID- 16107559
TI  - Live imaging of Drosophila brain neuroblasts reveals a role for Lis1/dynactin in
      spindle assembly and mitotic checkpoint control.
AB  - Lis1 is required for nuclear migration in fungi, cell cycle progression in
      mammals, and the formation of a folded cerebral cortex in humans. Lis1 binds
      dynactin and the dynein motor complex, but the role of Lis1 in many
      dynein/dynactin-dependent processes is not clearly understood. Here we generate
      and/or characterize mutants for Drosophila Lis1 and a dynactin subunit, Glued, to
      investigate the role of Lis1/dynactin in mitotic checkpoint function. In
      addition, we develop an improved time-lapse video microscopy technique that
      allows live imaging of GFP-Lis1, GFP-Rod checkpoint protein, green fluorescent
      protein (GFP)-labeled chromosomes, or GFP-labeled mitotic spindle dynamics in
      neuroblasts within whole larval brain explants. Our mutant analyses show that
      Lis1/dynactin have at least two independent functions during mitosis: first
      promoting centrosome separation and bipolar spindle assembly during
      prophase/prometaphase, and subsequently generating interkinetochore tension and
      transporting checkpoint proteins off kinetochores during metaphase, thus
      promoting timely anaphase onset. Furthermore, we show that Lis1/dynactin/dynein
      physically associate and colocalize on centrosomes, spindle MTs, and
      kinetochores, and that regulation of Lis1/dynactin kinetochore localization in
      Drosophila differs from both Caenorhabditis elegans and mammals. We conclude that
      Lis1/dynactin act together to regulate multiple, independent functions in mitotic
      cells, including spindle formation and cell cycle checkpoint release.

PMID- 16107560
TI  - CD74 is a member of the regulated intramembrane proteolysis-processed protein
      family.
AB  - Quite a few regulatory proteins, including transcription factors, are normally
      maintained in a dormant state to be activated after internal or environmental
      cues. Recently, a novel strategy, requiring proteolytic cleavage, was described
      for the mobilization of dormant transcription factors. These transcription
      factors are initially synthesized in an inactive form, whereas "nesting" in
      integral membrane precursor proteins. After a cleavage event, these new active
      factors are released from the membrane and can migrate into the nucleus to drive
      regulated gene transcription. This mechanism, regulated intramembrane proteolysis
      (RIP), controls diverse biological processes in prokaryotes and eukaryotes in
      response to a variety of signals. The MHC class II chaperone, CD74 (invariant
      chain, Ii), was previously shown to function as a signaling molecule in several
      pathways. Recently, we demonstrated that after intramembranal cleavage, the CD74
      cytosolic fragment (CD74-ICD) is released and induces activation of transcription
      mediated by the NF-kappaB p65/RelA homodimer and the B-cell-enriched coactivator,
      TAF(II)105. Here, we add CD74 to the growing family of RIP-processed proteins.
      Our studies show that CD74 ectodomain must be processed in the endocytic
      compartments to allow its intramembrane cleavage that liberates CD74
      intracellular domain (CD74-ICD). We demonstrate that CD74-ICD translocates to the
      nucleus and induces the activation of the p65 member of NF-kappaB in this
      compartment.

PMID- 16107561
TI  - The C-terminal tail of the polycystin-1 protein interacts with the Na,K-ATPase
      alpha-subunit.
AB  - Polycystin-1 (PC-1) is the product of the PKD1 gene, which is mutated in
      autosomal dominant polycystic kidney disease. We show that the Na,K-ATPase alpha
      subunit interacts in vitro and in vivo with the final 200 amino acids of the
      polycystin-1 protein, which constitute its cytoplasmic C-terminal tail.
      Functional studies suggest that this association may play a role in the
      regulation of the Na,K-ATPase activity. Chinese hamster ovary cells stably
      expressing the entire PC-1 protein exhibit a dramatic increase in Na,K-ATPase
      activity, although the kinetic properties of the enzyme remain unchanged. These
      data indicate that polycystin-1 may contribute to the regulation of Na,K-ATPase
      activity in kidneys in situ, thus modulating renal tubular fluid and electrolyte
      transport.

PMID- 16107562
TI  - A role for Fis1 in both mitochondrial and peroxisomal fission in mammalian cells.
AB  - The mammalian dynamin-like protein DLP1/Drp1 has been shown to mediate both
      mitochondrial and peroxisomal fission. In this study, we have examined whether
      hFis1, a mammalian homologue of yeast Fis1, which has been shown to participate
      in mitochondrial fission by an interaction with DLP1/Drp1, is also involved in
      peroxisomal growth and division. We show that hFis1 localizes to peroxisomes in
      addition to mitochondria. Through differential tagging and deletion experiments,
      we demonstrate that the transmembrane domain and the short C-terminal tail of
      hFis1 is both necessary and sufficient for its targeting to peroxisomes and
      mitochondria, whereas the N-terminal region is required for organelle fission.
      hFis1 promotes peroxisome division upon ectopic expression, whereas silencing of
      Fis1 by small interfering RNA inhibited fission and caused tubulation of
      peroxisomes. These findings provide the first evidence for a role of Fis1 in
      peroxisomal fission and suggest that the fission machinery of mitochondria and
      peroxisomes shares common components.

PMID- 16107563
TI  - Cell-matrix entanglement and mechanical anchorage of fibroblasts in three
      dimensional collagen matrices.
AB  - Fibroblast-3D collagen matrix culture provides a physiologically relevant model
      to study cell-matrix interactions. In tissues, fibroblasts are phagocytic cells,
      and in culture, they have been shown to ingest both fibronectin and collagen
      coated latex particles. Compared with cells on collagen-coated coverslips,
      phagocytosis of fibronectin-coated beads by fibroblasts in collagen matrices was
      found to be reduced. This decrease could not be explained by integrin
      reorganization, tight binding of fibronectin beads to the collagen matrix, or
      differences in overall bead binding to the cells. Rather, entanglement of
      cellular dendritic extensions with collagen fibrils seemed to interfere with the
      ability of the extensions to interact with the beads. Moreover, once these
      extensions became entangled in the matrix, cells developed an integrin
      independent component of adhesion. We suggest that cell-matrix entanglement
      represents a novel mechanism of cell anchorage that uniquely depends on the three
      dimensional character of the matrix.

PMID- 16107564
TI  - Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.
AB  - The aim of this study was to characterize the role of the efflux transporter Mrp2
      (Abcc2) in the pharmacokinetics of orally and intravenously administered
      pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were
      given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type
      animals were studied after intravenous administration of pravastatin (5 mg/kg).
      The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration
      time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7
      fold higher AUC (p < 0.01) after intravenous administration of pravastatin as
      compared with the wild-type animals. The mean systemic (total) clearance of
      pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean
      V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The
      mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as
      compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The
      increased systemic exposure to oral pravastatin in the TR- rats was associated
      with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as
      shown by smaller lathosterol to cholesterol concentration ratios. These results
      suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR-
      rats is partly compensated for by increased urinary excretion of pravastatin.
      Furthermore, intestinal Mrp2 does not appear to play a major role in the oral
      absorption of pravastatin in normal rats.

PMID- 16107565
TI  - Questions raised about private insurance.

PMID- 16107566
TI  - Age at menarche in relation to adult height: the EPIC study.
AB  - In the last two centuries, age at menarche has decreased in several European
      populations, whereas adult height has increased. It is unclear whether these
      trends have ceased in recent years or how age at menarche and height are related
      in individuals. In this study, the authors first investigated trends in age at
      menarche and adult height among 286,205 women from nine European countries by
      computing the mean age at menarche and height in 5-year birth cohorts, adjusted
      for differences in socioeconomic status. Second, the relation between age at
      menarche and height was estimated by linear regression models, adjusted for age
      at enrollment between 1992 and 1998 and socioeconomic status. Mean age at
      menarche decreased by 44 days per 5-year birth cohort (beta = -0.12, standard
      error = 0.002), varying from 18 days in the United Kingdom to 58 days in Spain
      and Germany. Women grew 0.29 cm taller per 5-year birth cohort (standard error =
      0.007), varying from 0.42 cm in Italy to 0.98 cm in Denmark. Furthermore, women
      grew approximately 0.31 cm taller when menarche occurred 1 year later (range by
      country: 0.13-0.50 cm). Based on time trends, more recent birth cohorts have
      their menarche earlier and grow taller. However, women with earlier menarche
      reach a shorter adult height compared with women who have menarche at a later
      age.

PMID- 16107567
TI  - Homocysteine and cognitive performance in the Framingham offspring study: age is
      important.
AB  - Plasma total homocysteine (tHcy) concentrations are associated with deficits in
      cognitive performance in persons free from dementia. The extent to which age
      modifies these associations is in need of further investigation in large,
      community-based, prospective studies combining the following elements: 1)
      multiple cognitive tests; 2) statistical adjustment for the role of the vitamin
      cofactors folate, vitamin B6, and vitamin B12; and 3) adjustment for the presence
      of risk factors for cardiovascular disease and stroke. Using data collected
      between 1991 and 2002, the authors investigated the associations between tHcy and
      multiple measures of cognitive performance in 2,096 dementia- and stroke-free
      participants of the Framingham Offspring Study, who were stratified into three
      age groups (40-49 years, 50-59 years, 60-82 years), after findings of
      statistically significant tHcy-by-age interactions for multiple cognitive
      measures. Regardless of statistical adjustment for age, sex, gender, the vitamin
      cofactors, and cardiovascular risk factors, statistically significant inverse
      associations between tHcy and multiple cognitive domains were observed for
      individuals aged 60 or more years; no such associations were observed for
      participants aged less than 60 years. Early preventive interventions may be
      important, because the inverse association between tHcy and cognitive performance
      is observed beyond middle age.

PMID- 16107568
TI  - Identifying pediatric age groups for influenza vaccination using a real-time
      regional surveillance system.
AB  - Evidence is accumulating that universal vaccination of schoolchildren would
      reduce the transmission of influenza. The authors sought to identify target age
      groups within the pediatric population that develop influenza the earliest and
      are most strongly linked with mortality in the population. Patient visits for
      respiratory illness were monitored, using real-time syndromic surveillance
      systems, in six Massachusetts health-care settings, including ambulatory care
      sites and emergency departments at tertiary-care and community hospitals. Visits
      from January 1, 2000, to September 30, 2004, were segmented into age group
      subpopulations. Timeliness and prediction of each subpopulation were measured
      against pneumonia and influenza mortality in New England with time-series
      analyses and regression models. Study results show that patient age significantly
      influences timeliness (p = 0.026), with pediatric age groups arriving first (p <
      0.001); children aged 3-4 years are consistently the earliest (p = 0.0058). Age
      also influences the degree of prediction of mortality (p = 0.036), with illness
      among children under age 5 years, compared with all other patients, most strongly
      associated with mortality (p < 0.001). Study findings add to a growing body of
      support for a strategy to vaccinate children older than the currently targeted
      age of 6-23 months and specifically suggest that there may be value in
      vaccinating preschool-age children.

PMID- 16107569
TI  - Re: "Long-term mobile phone use and brain tumor risk".

PMID- 16107570
TI  - Re: "Long-term mobile phone use and brain tumor risk".

PMID- 16107571
TI  - Re: "Long-term mobile phone use and brain tumor risk".

PMID- 16107572
TI  - Upper respiratory symptoms and other health effects among residents living near
      the World Trade Center site after September 11, 2001.
AB  - The authors investigated changes in respiratory health after September 11, 2001
      ("9/11") among residents of the area near the World Trade Center (WTC) site in
      New York City as compared with residents of a control area. In 2002, self
      administered questionnaires requesting information on the presence and
      persistence of respiratory symptoms, unplanned medical visits, and medication use
      were sent to 9,200 households (22.3% responded) within 1.5 km of the WTC site
      (affected area) and approximately 1,000 residences (23.3% responded) in Upper
      Manhattan, more than 9 km from the site (control area). Residents of the affected
      area reported higher rates of new-onset upper respiratory symptoms after 9/11
      (cumulative incidence ratio = 2.22, 95% confidence interval (CI): 1.88, 2.63).
      Most of these symptoms persisted 1 year after 9/11 in the affected area.
      Previously healthy residents of the affected area had more respiratory-related
      unplanned medical visits (prevalence ratio = 1.73, 95% CI: 1.13, 2.64) and more
      new medication use (prevalence ratio = 2.89, 95% CI: 1.75, 4.76) after 9/11.
      Greater impacts on respiratory functional limitations were also found in the
      affected area. Although bias may have contributed to these increases, other
      analyses of WTC-related pollutants support their biologic plausibility. Further
      analyses are needed to examine whether these increases were related to
      environmental exposures and to monitor long-term health effects.

PMID- 16107573
TI  - No bit PARt for PAR-1.

PMID- 16107574
TI  - Pathogenesis of lung cancer: 100 year report.
AB  - Over the past 100 years, our understanding of the pathogenesis of lung cancer has
      advanced impressively. Environmental carcinogens and a gene locus determining
      susceptibility have been identified. The pathology of lung cancer has been
      classified into categories with major clinical implications. The cellular and
      molecular genetic changes underlying lung cancer have become better understood
      over the past 25 years, but the stepwise progression of respiratory epithelium
      from normal to neoplastic is not yet well demarcated, limiting abilities to
      advance early detection and chemoprevention. The translation of improved
      understanding of dominant signal transduction pathways in lung cancer to
      rationally designed therapeutic strategies has had recent successes,
      demonstrating a proof of principle for targeted therapy in lung cancer.
      Improvement in overall patient outcomes has been stubbornly slow and will require
      concerted efforts.

PMID- 16107575
TI  - The role of prostaglandin D receptor gene in asthma pathogenesis.

PMID- 16107576
TI  - Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte
      depletion in rats expressing human diphtheria toxin receptor transgene.
AB  - Glomerular injury and proteinuria in diabetes (types 1 and 2) and IgA nephropathy
      is related to the degree of podocyte depletion in humans. For determining the
      causal relationship between podocyte depletion and glomerulosclerosis, a
      transgenic rat strain in which the human diphtheria toxin receptor is
      specifically expressed in podocytes was developed. The rodent homologue does not
      act as a diphtheria toxin (DT) receptor, thereby making rodents resistant to DT.
      Injection of DT into transgenic rats but not wild-type rats resulted in dose
      dependent podocyte depletion from glomeruli. Three stages of glomerular injury
      caused by podocyte depletion were identified: Stage 1, 0 to 20% depletion showed
      mesangial expansion, transient proteinuria and normal renal function; stage 2, 21
      to 40% depletion showed mesangial expansion, capsular adhesions (synechiae),
      focal segmental glomerulosclerosis, mild persistent proteinuria, and normal renal
      function; and stage 3, >40% podocyte depletion showed segmental to global
      glomerulosclerosis with sustained high-grade proteinuria and reduced renal
      function. These pathophysiologic consequences of podocyte depletion parallel
      similar degrees of podocyte depletion, glomerulosclerosis, and proteinuria seen
      in diabetic glomerulosclerosis. This model system provides strong support for the
      concept that podocyte depletion could be a major mechanism driving
      glomerulosclerosis and progressive loss of renal function in human glomerular
      diseases.

PMID- 16107577
TI  - Interactions between renin angiotensin system and advanced glycation in the
      kidney.
AB  - Although hemodynamic and metabolic factors are individually implicated in the
      development of diabetic nephropathy, their interaction has not been defined
      clearly. In this study, the effects of angiotensin II (Ang II) and advanced
      glycation end products (AGE) both individually on each other are explored and
      compared. In the first study arm, Sprague-Dawley rats received a continuous
      infusion of AGE-modified rat serum albumin (RSA) or unmodified RSA for 4 wk with
      or without the angiotensin receptor type 1 antagonist valsartan. In the second
      arm, animals received a continuous infusion of Ang II (58.3 ng/kg per min) with
      or without the AGE inhibitor pyridoxamine. Components of the intrarenal renin
      angiotensin system were measured using real time reverse transcription-PCR,
      immunohistochemistry, and standard angiotensin-converting enzyme (ACE) activity
      assays. Renal and serum AGE were quantified by immunohistochemistry, ELISA, and
      AGE-fluorescence. After an infusion of AGE-RSA, renal expression of
      angiotensinogen, ACE, renin, and angiotensin receptor type 1 were increased
      significantly (all P < 0.01), and ACE activity was elevated. This was associated
      with tubular and glomerular hypertrophy and AGE accumulation, which could be
      antagonized by valsartan. However, valsartan had no effect on increased
      filtration fraction associated with an AGE-RSA infusion. At the same time, an
      infusion of Ang II increased the serum and renal accumulation of AGE and advanced
      oxidation protein products and induced renal hypertrophy and salt retention that
      could be antagonized by pyridoxamine. However, pyridoxamine had no effect on
      renal vasoconstriction manifested by reduced renal blood flow. AGE and Ang II
      have overlapping activities in the kidney. The beneficial effects of blockade of
      either pathway underline the importance of this interaction in diabetic renal
      disease and the aging kidney.

PMID- 16107578
TI  - Novel TRPM6 mutations in 21 families with primary hypomagnesemia and secondary
      hypocalcemia.
AB  - Primary hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive
      disorder characterized by profound hypomagnesemia associated with hypocalcemia.
      Pathophysiology is related to impaired intestinal absorption of magnesium
      accompanied by renal magnesium wasting as a result of a reabsorption defect in
      the distal convoluted tubule. Recently, mutations in the TRPM6 gene coding for
      TRPM6, a member of the transient receptor potential (TRP) family of cation
      channels, were identified as the underlying genetic defect. Here, the results of
      a TRPM6 mutational analysis of 21 families with 28 affected individuals are
      presented. In this large patient cohort, a retrospective clinical evaluation
      based on a standardized questionnaire was also performed. Genotype analysis
      revealed TRPM6 mutations in 37 of 42 expected mutant alleles. Sixteen new TRPM6
      mutations were identified, including stop mutations, frame-shift mutations,
      splice-site mutations, and deletions of exons. Electrophysiologic analysis of
      mutated ion channels after heterologous expression in Xenopus oocytes proved
      complete loss of function of TRPM6. Clinical evaluation revealed a homogeneous
      clinical picture at manifestation with onset in early infancy with generalized
      cerebral convulsions. Initial laboratory evaluation yielded extremely low serum
      magnesium levels, low serum calcium levels, and inadequately low parathyroid
      hormone levels. Treatment usually consisted of acute intravenous magnesium
      supplementation leading to relief of clinical symptoms and normocalcemia,
      followed by lifelong oral magnesium supplementation. Serum magnesium levels
      remained in the subnormal range despite adequate therapy. This is best explained
      by a disturbed magnesium conservation in the distal convoluted tubule, which
      emerged in all patients upon magnesium supplementation. Delay of diagnosis
      resulted in permanent neurologic damage in three patients.

PMID- 16107579
TI  - Molecular mechanisms of impaired urinary concentrating ability in glucocorticoid
      deficient rats.
AB  - The purpose of this study was to examine urinary concentrating ability and
      protein expression of renal aquaporins and ion transporters in glucocorticoid
      deficient (GD) rats in response to water deprivation as compared with control
      rats. Rats underwent bilateral adrenalectomies, followed only by aldosterone
      replacement (GD) or both aldosterone and dexamethasone replacement (control). As
      compared with control rats, the GD rats demonstrated a decrease in cardiac output
      and mean arterial pressure. In response to 36-h water deprivation, GD rats
      demonstrated significantly greater urine flow rate and decreased urine osmolality
      as compared with control rats at comparable serum osmolality and plasma
      vasopressin concentrations. The initiator of the countercurrent concentrating
      mechanism, the sodium-potassium-2 chloride co-transporter, was significantly
      decreased, as was the medullary osmolality in the GD rats versus control rats.
      There was also a decrease in inner medulla aquaporin-2 (AQP2) and urea
      transporter A1 (UT-A1) in GD rats as compared with control rats. There was a
      decrease in outer medulla Gsalpha protein, an important factor in vasopressin
      mediated regulation of AQP2. Immunohistochemistry studies confirmed the decreased
      expression of AQP2 and UT-A1 in kidneys of GD rats as compared with control. In
      summary, impairment in the urinary concentrating mechanism was documented in GD
      rats in association with impaired countercurrent multiplication, diminished
      osmotic equilibration via AQP2, and diminished urea equilibration via UT-A1.
      These events occurred primarily in the relatively oxygen-deficient medulla and
      may have been initiated, at least in part, by the decrease in mean arterial
      pressure and thus renal perfusion pressure in this area of the kidney.

PMID- 16107580
TI  - Glucose metabolism in renal transplant recipients: effect of calcineurin
      inhibitor withdrawal and conversion to sirolimus.
AB  - Cyclosporine A (CsA) and tacrolimus have been associated with an increased risk
      for diabetes after transplantation, whereas sirolimus is deemed to be devoid of
      any effect on glucose metabolism. This study was performed to investigate the
      effect of the withdrawal of calcineurin inhibitors and the switch to sirolimus on
      peripheral insulin resistance and pancreatic beta cell response. Twenty-six
      patients who received a kidney transplant and discontinued CsA and were converted
      to sirolimus and 15 recipients of suboptimal kidneys who were treated with
      tacrolimus plus sirolimus for the first 3 mo after grafting and thereafter with
      sirolimus alone were enrolled. All patients underwent an oral glucose tolerance
      test and intravenous insulin tolerance test before and 6 mo after the conversion
      to sirolimus-alone therapy. The withdrawal of CsA or tacrolimus was associated
      with a significant fall of insulin sensitivity (both P = 0.01) and with a defect
      in the compensatory beta cell response, as measured by the disposition index (P =
      0.004 and P = 0.02, respectively). The increase of insulin resistance and the
      decrease of disposition index significantly correlated with the change of serum
      triglyceride concentration after the conversion to sirolimus-based therapy (R(2)
      = 0.30, P = 0.0002; and R(2) = 0.19, P = 0.004, respectively). Clinically, the
      switch to sirolimus was associated with a 30% increase of incidence of impaired
      glucose tolerance and with four patients' developing new-onset diabetes. In
      conclusion, the discontinuation of calcineurin inhibitors and their replacement
      by sirolimus fail to ameliorate the glycometabolic profile of kidney transplant
      recipients. Rather, it is associated with a worsening of insulin resistance and
      an inappropriately low insulin response.

PMID- 16107581
TI  - Redistribution of myosin VI from top to base of proximal tubule microvilli during
      acute hypertension.
AB  - During acute hypertension, Na(+)/H(+) exchangers (NHE3) retract from top to base
      of proximal tubule microvilli (MV) and Na(+) reabsorption decreases in proximal
      tubule. This study aimed to determine whether the actin-based motor myosin VI
      coordinately retracts with NHE3 in response to acute hypertension. BP was raised
      approximately 50 mmHg in rats for 20 to 30 min or sham treated, and kidneys were
      analyzed by subcellular fractionation or microscopy. During acute hypertension,
      myosin VI redistributed from low density apical MV-enriched membranes (from 23 +/
      2.4 to 11.4 +/- 2.2%) into higher density membranes (from 23.2 +/- 0.7 to 36.9
      +/- 2.6%). By confocal microscopy, myosin VI was detected over the whole length
      of the MV in controls, then became completely focused at the base of MV during
      acute hypertension. For electron microscopic analysis using immunogold labeling,
      MV were divided into five zones from top (z1) to base (z5). In controls, myosin
      VI was evenly distributed through the five MV zones. In acute hypertension,
      myosin VI decreased in z1 (from 20.6 +/- 1.9 to 10.5 +/- 2.3%) and z2 (from 21.0
      +/- 2.0 to 13.2 +/- 1.4%) and increased in z5 (from 21.1 +/- 3.3 to 38.6 +/-
      3.0%). These results provide the first observation that acute hypertension causes
      myosin VI redistribution and support the idea that myosin VI may serve as the
      molecular motor for NHE3 retraction from top to base of MV during acute
      hypertension.

PMID- 16107582
TI  - Circulating inflammatory endothelial cells contribute to endothelial progenitor
      cell dysfunction in patients with vasculitis and kidney involvement.
AB  - Impaired angiogenic function has been reported in patients with kidney failure.
      During vascular damage, endothelial cells may detach from the site of
      inflammation and be released into the peripheral blood. With the use of Wegener's
      granulomatosis as a study model, whether circulating inflammatory endothelial
      cells (IEC) can (1) be used as a disease activity marker and (2) contribute to
      sustained vascular damage by inducing endothelial progenitor cell (EPC)
      dysfunction were examined. IEC-defined as endothelial cells that express the two
      inflammatory-associated markers vascular-adhesion protein-1 (VAP-1) and MHC class
      I-related chain A (MICA)-were increased significantly in patients with active
      disease as compared with those in remission. IEC expressed high levels of
      inducible nitric oxide synthase and neutrophil-activating chemokines, such as
      macrophage inflammatory protein-1alpha, growth-related oncogene-alpha, epithelial
      neutrophil activating peptide-78, and IL-8, and induced increased neutrophil
      migration. IEC levels significantly correlated with C-reactive protein and extent
      of organ involvement. Patients with active disease had decreased numbers of EPC
      colony-forming units and a high expression of VAP-1 and MICA in kidney
      endothelium. EPC did not express VAP-1 or MICA. IEC significantly inhibited
      proliferation, migration, and endothelial nitric oxide synthase expression in
      EPC. Thus, apart from being a new disease activity marker, IEC may contribute to
      vascular damage by impairing the functional capacity for repair by EPC. IEC may
      provide a unique in vitro system to study pathogenesis of kidney and vascular
      diseases.

PMID- 16107583
TI  - Determinants of glomerular volume in different cortical zones of the human
      kidney.
AB  - Enlarged glomerular size is a feature of focal segmental glomerulosclerosis,
      obesity-related glomerulopathy, diabetic nephropathy, and hypertension. The
      distribution of glomerular volumes within different cortical zones and glomerular
      volume alterations with age and obesity may contribute to understanding the
      evolution of these diseases. We analyzed the distributions of volumes of
      individual glomeruli in the superficial, middle, and juxtamedullary cortex of
      normal human kidneys using the disector/Cavalieri method. Volumes (V(glom)) of
      720 nonsclerotic glomeruli (30 per kidney, 10 per zone) were estimated in autopsy
      kidneys of 24 American men, 12 aged 20 to 30 yr and 12 aged 51 to 69 yr. Black
      and white individuals were represented equally. The range of individual V(glom)
      within subjects varied from two- to eight-fold. There were no significant zonal
      differences in V(glom) in the young or those with body surface area (BSA) < or =
      2.11 m(2). In contrast, superficial glomeruli in the older age group, in those
      with BSA > 2.11 m(2), and in white subjects were significantly larger than
      juxtamedullary glomeruli. Black subjects tended toward larger V(glom) than white
      subjects, and this difference was significant and most marked in the
      juxtamedullary zone and independent of age, BSA, and glomerular number. There is
      a wide range in individual V(glom) in adults. BSA, race, and age independently
      influence V(glom) in different zones of the renal cortex. These findings might
      reflect processes of aging and susceptibility factors to renal disease.

PMID- 16107584
TI  - Applying new approaches from cognitive neuroscience to enhance drug development
      for the treatment of impaired cognition in schizophrenia.
AB  - New approaches to the measurement of cognition in schizophrenia include the use
      of tasks from experimental cognitive psychology to examine the integrity of
      specific cognitive systems and the application of these tasks in noninvasive
      neuroimaging (e.g., functional magnetic resonance imaging [fMRI]) studies that
      directly measure the effects of drugs on cognition-related brain activity. These
      approaches offer many advantages, including the isolation of specific cognitive
      systems that may be conserved across species; controlling for the confounding
      effects of generalized performance deficits such as poor motivation, sedation,
      and so on; and providing a direct translational bridge from studies using animal
      models of cognition to patient-based research using fMRI. These developments have
      the potential to transform the early human phases of drug development and
      streamline the decision making at this critical point in the process. As was the
      case for the Measurement and Treatment Research to Improve Cognition in
      Schizophrenia initiative, optimizing the application of cognitive neuroscience to
      new drug development will require a major commitment by multiple investigators to
      task development and a thorough psychometric evaluation of both behavioral and
      neuroimaging measures.

PMID- 16107585
TI  - Synthesizing schizophrenia: a bottom-up, symptomatic approach.
AB  - The cognitive deficits in schizophrenia are discussed in terms of the other
      symptoms of the disorder, as well as according to a translational approach that
      involves using similar or analogous tests for humans and experimental animals.
      This approach, it is argued, will enable the testing of novel drugs and the
      development of adequate etiological models of schizophrenia.

PMID- 16107586
TI  - Cortical intrinsic circuits can support activity propagation through an
      isofrequency strip of the guinea pig primary auditory cortex.
AB  - A pure tone evokes propagating activities in a strip of the primary auditory
      cortex (AI), an isofrequency strip (IS). A fundamental issue concerns the roles
      that thalamocortical input and intracortical connectivity play in generating the
      activities. Here we addressed this issue in guinea pigs using in vivo and in
      vitro real-time optical imaging techniques. As reported previously, tone-evoked
      activity propagated dorsoventrally along a strip (an IS) in AI. We found that an
      electrical pulse applied focally within the strip, triggered activity propagation
      with a spatiotemporal pattern highly similar to tone-evoked activation. The
      propagation velocity of electrically evoked activity was significantly slower
      than that of tone-evoked activity, but was comparable to the velocity of lateral
      activity propagation in cortical slices, suggesting that the electrically evoked
      activity propagation in vivo is mediated by intracortical circuits. To test this
      notion, we lesioned the auditory thalamus chemically; in such animals,
      electrically evoked activity in AI was not affected, although tone-evoked
      activity was abolished. Further, in slices of the AI, the extent of electrically
      evoked activity propagation in layer II/III was significantly larger in coronal
      slices than in horizontal slices. Together, our results suggest that
      intracortical connectivity in AI enables a focally evoked activity to propagate
      throughout an IS.

PMID- 16107587
TI  - MEG phase follows conscious perception during binocular rivalry induced by visual
      stream segregation.
AB  - We have investigated an unusual form of binocular rivalry between two images that
      are flickered one to each eye, but are never presented simultaneously to the
      observer. The images were presented in alternation, with a brief dark period
      between the images. When the flicker frequency was < 5 Hz, the subjects primarily
      experienced a unitary flicker that alternated between the two images. When the
      flicker frequency was > 5 Hz, the subjects primarily experienced two single-image
      flickers that rival. We investigated magnetoencephalography (MEG) responses at
      the flicker frequency of the rival stimuli. We found that at some recording
      locations responses are phase-locked to the flicker that is consciously being
      perceived. At each flicker rate that induced rivalry, phase shifts following the
      conscious percept were found consistently at MEG sensors over midline frontal
      lobe. Most of these sensors show higher magnitude responses when two rivaling
      flickers are perceived than when a unitary alternating color flicker is
      perceived. At sensors over occipital lobe, the sensor locations that phase-locked
      to the perceived flicker depended on the color, orientation, and frequency of
      flicker. By contrast, sensors over parietal cortex respond preferentially to one
      flicker, even as the conscious percept changes. Apparently, a large-scale network
      of cell assemblies in occipital and frontal cortex, responds preferentially to
      the perceived stimulus during rivalry, and is sensitive to the timing of the
      flicker driving the conscious percept.

PMID- 16107588
TI  - Dendritic branch typing and spine expression patterns in cortical nonpyramidal
      cells.
AB  - To understand the dendritic differentiation in various types of cortical
      nonpyramidal cells, we analyzed quantitatively their dendritic branching and
      spine expression. The dendritic internode and interspine interval obeyed
      exponential distributions with type-specific decay constants. The initial
      branching pattern, internode interval and spine density at the light microscopic
      level divided nonpyramidal cells into three dendritic types, correlated with
      axonal, neurochemical and firing types. The initial branching pattern determined
      the overall vertical spread of dendrites. Basket cell subtypes with different
      firing and chemical expression patterns were distinct in the vertical and
      horizontal spatial spread, providing diverse input territories. Internode
      densities of dendritic spines, as well as those of axonal synaptic boutons, did
      not correlate with the tortuosities and intervals, suggesting a tendency to
      distribute synapses homogeneously over the arbor. Dendritic spines identified at
      the electron microscopic level were different in length and shape among subtypes.
      Although the density was lower than that of pyramidal cells, spines themselves
      were also composed of several morphological types such as mushroom and multihead
      ones, which were expressed differentially among subtypes. Correlation of
      dendritic branching characteristics with differences in spine structure suggests
      distinct ways to receive specific inputs among the subtypes.

PMID- 16107589
TI  - Impact of cortical network activity on short-term synaptic depression.
AB  - Repetitive stimulation of synaptic connections in the cerebral cortex often
      induces short-term synaptic depression (STD), a property directly related to the
      probability of transmitter release and critical for the computational properties
      of the network. In order to explore how spontaneous activity in the network
      affects this property, we first studied STD in cortical slices that were either
      silent or that displayed spontaneous rhythmic slow oscillations resembling those
      recorded during slow wave sleep in vivo. STD was considerably reduced by the
      occurrence of spontaneous rhythmic activity in the cortical network. Once the
      rhythmic activity started, depression decreased over time in parallel with the
      duration and intensity of the ongoing activity until a plateau was reached.
      Thalamocortical and intracortical synaptic potentials studied in vivo also showed
      stronger depression in a silent than in an active cortical network, and the
      depression values in the active cortical network in vivo were indistinguishable
      from those found in active slices in vitro. We suggest that this phenomenon is
      due to the different steady states of the synapses in active and in silent
      networks.

PMID- 16107590
TI  - Human SNPs reveal no evidence of frequent positive selection.
AB  - We compared the single-nucleotide polymorphisms (SNPs) in humans in 182
      housekeeping and 148 tissue-specific genes. SNPs were divided into rare and
      common polymorphisms based on their frequencies. We found that housekeeping genes
      tend to be less polymorphic than tissue-specific genes for both rare and common
      SNPs. Using mouse as a second species for computing sequence divergences, we
      found no evidence of positive selection: for both housekeeping and tissue
      specific genes, the ratio of nonsynonymous to synonymous common SNPs per site
      showed no significant difference from that of divergence. Similarly, we observed
      no evidence of positive selection for the 289 and 149 genes that have orthologs
      available for divergence calculation between humans and chimpanzees and between
      humans and Old World monkeys, respectively. A comparison with previous SNP
      studies suggests that approximately 20% of the nonsynonymous SNPs in the human
      population are nearly neutral and that positive selection in the human genome
      might not be as frequent as previously thought.

PMID- 16107591
TI  - Statistical alignment of retropseudogenes and their functional paralogs.
AB  - We describe a model for the sequence evolution of a processed pseudogene and its
      paralog from a common protein-coding ancestor. The model accounts for
      substitutions, insertions, and deletions and combines nucleotide- and codon-level
      mutation models. We give a dynamic programming method for calculating the
      likelihood of homology between two sequences in the model and describe the
      accompanying alignment algorithm. We also describe how ancestral codons can be
      computed when the same gene produced multiple pseudogene homologs. We apply our
      methods to the evolution of human cytochrome c.

PMID- 16107592
TI  - Evaluation of an improved branch-site likelihood method for detecting positive
      selection at the molecular level.
AB  - Detecting positive Darwinian selection at the DNA sequence level has been a
      subject of considerable interest. However, positive selection is difficult to
      detect because it often operates episodically on a few amino acid sites, and the
      signal may be masked by negative selection. Several methods have been developed
      to test positive selection that acts on given branches (branch methods) or on a
      subset of sites (site methods). Recently, Yang, Z., and R. Nielsen (2002. Codon
      substitution models for detecting molecular adaptation at individual sites along
      specific lineages. Mol. Biol. Evol. 19:908-917) developed likelihood ratio tests
      (LRTs) based on branch-site models to detect positive selection that affects a
      small number of sites along prespecified lineages. However, computer simulations
      suggested that the tests were sensitive to the model assumptions and were unable
      to distinguish between relaxation of selective constraint and positive selection
      (Zhang, J. 2004. Frequent false detection of positive selection by the likelihood
      method with branch-site models. Mol. Biol. Evol. 21:1332-1339). Here, we describe
      a modified branch-site model and use it to construct two LRTs, called branch-site
      tests 1 and 2. We applied the new tests to reanalyze several real data sets and
      used computer simulation to examine the performance of the two tests by examining
      their false-positive rate, power, and robustness. We found that test 1 was unable
      to distinguish relaxed constraint from positive selection affecting the lineages
      of interest, while test 2 had acceptable false-positive rates and appeared robust
      against violations of model assumptions. As test 2 is a direct test of positive
      selection on the lineages of interest, it is referred to as the branch-site test
      of positive selection and is recommended for use in real data analysis. The test
      appeared conservative overall, but exhibited better power in detecting positive
      selection than the branch-based test. Bayes empirical Bayes identification of
      amino acid sites under positive selection along the foreground branches was found
      to be reliable, but lacked power.

PMID- 16107593
TI  - Site-to-site variation of synonymous substitution rates.
AB  - We develop a new model for studying the molecular evolution of protein-coding DNA
      sequences. In contrast to existing models, we incorporate the potential for site
      to-site heterogeneity of both synonymous and nonsynonymous substitution rates. We
      demonstrate that within-gene heterogeneity of synonymous substitution rates
      appears to be common. Using the new family of models, we investigate the utility
      of a variety of new statistical inference procedures, and we pay particular
      attention to issues surrounding the detection of sites undergoing positive
      selection. We discuss how failure to model synonymous rate variation in the model
      can lead to misidentification of sites as positively selected.

PMID- 16107594
TI  - Dietary supplementation with orotate and uracil increases adaptive growth of
      jejunal mucosa after massive small bowel resection in rats.
AB  - BACKGROUND: Massive small-bowel resection (SBR) increases adaptive growth of
      residual intestine in animal models of short-bowel syndrome (SBS). Pyrimidine
      nucleotides are critical for DNA and RNA synthesis, but no previous study has
      evaluated whether supplementation of pyrimidines or their precursors in the diet
      enhances adaptive gut growth after SBR. This study determined growth responses in
      jejunal mucosa after 7 days of dietary supplementation with uracil, or its
      precursor, orotate, after massive SBR in rats. METHODS: Sprague-Dawley rats (
      approximately 200 g) underwent 80% jejunoileal resection (RX) or ileal
      transection (TX; control). Rats were pair-fed a purified (AIN-93G) powdered diet
      supplemented with or without 1% (wt/wt) orotate or uracil until killing at 7 days
      postsurgery. Defined jejunal segments were obtained for analysis of mucosal
      villus height (VH), crypt depth (CD), total mucosal height, bromodeoxyuridine
      (BrdU) incorporation, an index of cell proliferation, and full-thickness DNA and
      protein content as measures of intestinal adaptive growth. RESULTS: Jejunal VH
      increased significantly with SBR, as expected, and orotate further stimulated
      this response. Jejunal CD and total mucosal height increased significantly with
      both orotate and uracil supplementation compared with resected animals receiving
      standard diet. Orotate administration also increased jejunal DNA content compared
      with the increase observed with SBR alone. Finally, orotate, but not uracil,
      supplementation increased BrdU incorporation compared with resected rats fed
      standard or uracil-supplemented diet after SBR. CONCLUSIONS: Supplementation of
      oral diet with the pyrimidine precursor orotate and uracil stimulated adaptive
      jejunal growth after massive SBR in rats. Dietary orotate had more potent growth
      stimulatory effects than uracil in this animal model. Dietary supplementation
      with orotate and uracil represents a novel nutrition approach to enhance small
      bowel mucosal adaptive growth and absorptive capacity in SBS.

PMID- 16107595
TI  - Epidermal growth factor and/or growth hormone induce differential, side-specific
      signal transduction protein phosphorylation in enterocytes.
AB  - BACKGROUND: Epidermal growth factor (EGF) plus growth hormone (GH) enhances
      luminal glutamine transport into rabbit and human intestinal cells. Our objective
      was to screen for activation status of signal proteins in C2(BBe)1 cells
      (enterocyte-like cell line) in response to side-specific EGF or GH treatment and
      to investigate the dependence of EGF receptor (EGFR) phosphorylation status on
      its tyrosine kinase. METHODS: C2(BBe)1 cells on Transwells were treated for 15
      minutes on either the basolateral or apical-side with EGF or GH. Lysates
      underwent Kinetworks phospho site-screen-2.1 analysis (duplicate experiments). In
      addition, lysates from cells treated as above with or without tyrphostin AG1478
      (a specific EGFR tyrosine kinase inhibitor) underwent Western blot analysis for
      total EGFR and EGFR phosphorylated on tyrosine 1173, 1086 or 1068 (4-7
      experiments). RESULTS: Kinetworks phospho-screening demonstrated a broad range of
      interactions dependent on both side of exposure and protein studied. From this
      screen, it appears that ErbB2, Met, and insulin receptor (R)/insulin-like growth
      factor 1 R are not involved in the growth factors signals. For EGFR
      phosphorylation, basolateral, but not apical, EGF was a strong activator.
      Synergism was seen, but only with apical EGF plus basolateral GH. All EGFR
      phosphorylations were EGFR tyrosine kinase dependent. In contradistinction,
      apical EGF phosphorylated FAK and MAPKs. CONCLUSIONS: Kinetworks phosphoprotein
      screens can suggest pathways involved in side-specific and synergistic
      interaction between EGF and GH. For EGFR, synergism by EGF + GH was noticed only
      with Ap EGF plus Bl GH and was EGFR tyrosine kinase dependent. Adaptive
      intestinal responses due to enterally administrated EGF might be accelerated by
      the availability of parenteral GH.

PMID- 16107596
TI  - Parenteral nutrition-associated cholestasis in neonates: multivariate analysis of
      the potential protective effect of taurine.
AB  - BACKGROUND: Neonates receiving parenteral nutrition (PN) are at risk for PN
      associated cholestasis (PNAC); however, no preventive factors for PNAC have been
      clearly identified. Despite reports suggesting that taurine may prevent PNAC in
      neonates, such an effect of taurine has not yet been definitively demonstrated.
      We determined whether taurine supplementation reduces the incidence of PNAC in
      premature or critically ill neonates. METHODS: This study was part of a
      prospective, randomized, multi-institutional trial designed to assess
      cholecystokinin vs placebo as a potential preventive therapy of PNAC. Taurine
      supplementation of PN varied between institutions. The presence or absence of
      taurine in PN was analyzed by multivariate analysis, with a primary outcome
      measure of serum conjugated bilirubin (CB) as a measure of PNAC. RESULTS: Taurine
      reduced PNAC in premature infants (estimated maximum CB [95% confidence interval]
      0.50 mg/dL [-0.17 to 1.18] for those receiving taurine, vs 3.45 mg/dL [1.79-5.11]
      for neonates not receiving taurine, approaching significance, p = .07). Taurine
      significantly reduced PNAC in infants with necrotizing enterocolitis (NEC;
      estimated maximum CB 4.04 mg/dL [2.85-5.23], NEC infants receiving taurine, vs
      8.29 mg/dL [5.61-10.96], NEC infants not receiving taurine, p < .01). There were
      too few neonates with surgical anomalies to evaluate the effect of taurine in
      this group. CONCLUSIONS: Within specific subgroups of neonatal patients, taurine
      supplementation does offer a very significant degree of protection against PNAC.
      Patients with NEC or severe prematurity are most likely to benefit substantially
      from taurine supplementation.

PMID- 16107597
TI  - Dietary restriction compromises resistance to gut ischemia-reperfusion, despite
      reduction in circulating leukocyte activation.
AB  - BACKGROUND: Gut ischemia-reperfusion (gut I/R) accompanying severe surgical
      insults leads to neutrophil-mediated injury and is regarded as a triggering event
      in early multiple-organ failure. Our previous study demonstrated dietary
      restriction to down-regulate leukocyte activation. Therefore, we hypothesized
      dietary restriction might be beneficial in terms of surviving I/R. We also
      evaluated leukocyte activation and the level of organ glutathione, an
      antioxidative substance. METHODS: Institute of Cancer Research mice received
      chow, 170 (ad libitum), 119 (MR: mild restriction) or 68 (SR: severe restriction)
      g/kg per day for 7 days. Exp. 1: The mice (n = 59) underwent 15 or 45 minutes of
      gut ischemia and survival was observed. Exp. 2: The mice (n = 73) were killed
      before or 60 or 120 minutes after 15-minute ischemia. Reactive oxygen
      intermediate (ROI) production by circulating myeloid cells and CD11b expression
      was determined. Some mice were assessed for nuclear factor kappa B (NFkappaB)
      activation. Glutathione levels were measured in some of the small intestine and
      liver samples from each group. RESULTS: Dietary restriction decreased survival.
      Circulating myeloid cell priming and activation, in terms of ROI production and
      CD11b expression, were enhanced in the ad libitum group but not in the restricted
      groups. NFkappaB was activated only in the ad libitum group. Gut and hepatic
      glutathione levels were lower in the SR than in the ad libitum group. Dietary
      restriction caused histologic damages in gut, liver, and lung 120 minutes after
      reperfusion. CONCLUSIONS: Dietary restriction blunts leukocyte priming and
      activation after gut ischemic insult but worsens the outcome by, at least in
      part, decreasing antioxidative activities. Clinically, nutrition replenishment
      may be required to improve the outcome of gut hypoperfusion.

PMID- 16107598
TI  - The impact of a normoglycemic management protocol on clinical outcomes in the
      trauma intensive care unit.
AB  - BACKGROUND: The purpose of this study was to determine if protocol-driven
      normoglycemic management in trauma patients affected glucose control, ventilator
      associated pneumonia, surgical-site infection, and inpatient mortality. METHODS:
      A prospective, consecutive-series, historically controlled study design evaluated
      protocol-driven normoglycemic management among trauma patients at Vanderbilt
      University Medical Center. Those mechanically ventilated > or =24 hours and > or
      =15 years of age were included. A glycemic-control protocol required insulin
      infusion therapy for glucose >110 mg/dL. Control patients included those who met
      criteria, were admitted the year preceding protocol implementation, and had
      hyperglycemia treated at the physician's discretion. RESULTS: Eight hundred
      eighteen patients met study criteria; 383 were managed without protocol; 435
      underwent protocol. The protocol group had lower glucose levels 7 of 14 days
      measured. After admission, both groups had mean daily glucose levels <150 mg/dL.
      No difference in pneumonia (31.6% vs 34.5%; p = .413), surgical infection (5.0%
      vs 5.7%; p = .645) or mortality (12.3% vs 13.1%; p = .722) occurred between
      groups. If one episode of blood glucose level was > or =150 mg/dL (n = 638;
      78.0%), outcomes were worse: higher daily glucose levels for 14 days after
      admission (p < .001), pneumonia rates (35.9% vs 23.3%; p = .002), and mortality
      (14.6% vs 6.1%; p = .002). One or more days of glucose > or =150 mg/dL had a 2-
      to 3-fold increase in the odds of death. Protocol use in these patients was not
      associated with outcome improvement. CONCLUSIONS: Protocol-driven management
      decreased glucose levels 7 of 14 days after admission without outcome change. One
      or more glucose levels > or =150 mg/dL were associated with worse outcome.

PMID- 16107599
TI  - Latent copper deficiency in patients receiving low-copper enteral nutrition for a
      prolonged period.
AB  - BACKGROUND: Copper deficiency has been reported in patients supported with long
      term enteral nutrition. Occasionally, this leads to anemia and leukopenia. There
      is no detailed report relating to the onset time of copper deficiency and how the
      symptoms develop. This report describes the relation between copper deficiency
      symptoms and duration of enteral nutrition. METHODS: The study included 55
      patients, with 82 measurements, at the neurologic ward of Nagoya Daini Red Cross
      Hospital. The mean age was 71 +/- 11 years. The daily average dosage of energy
      was 938 kcal/d. A commercial nutrient for enteral administration that contains
      0.13 mg/1000 mL copper was used. Baseline measures on individual patients were
      taken every month. Blood was collected at 8 am before and after the start of
      enteral nutrition. Levels of copper, zinc, ceruloplasmin, hemoglobin, and white
      blood cells were measured. RESULTS: The serum level of copper in the patients was
      94.0-181.0 microg/dL before the start of enteral nutrition. The level of serum
      copper remained within the normal range for about 3 months. The level of serum
      copper in the patients decreased gradually and was less than the normal level
      after 3 months, with the exception of 1 patient. The serum level of copper in the
      patients was 3.0-123.0 microg/dL 3 months after the start of enteral nutrition.
      The levels of serum copper were below normal in 25 cases out of 82 measurements.
      However, the number of patients with symptoms of copper deficiency was only 2.
      Copper deficiency symptoms appeared at 41 and 77 months, the average being 59
      months. CONCLUSIONS: Almost all patients showed a latent copper deficiency about
      3 months after the start of enteral nutrition. However, only a few patients
      developed overt symptoms of copper deficiency.

PMID- 16107600
TI  - Parenteral nutrition as a risk factor for central venous catheter-related
      infection.
AB  - BACKGROUND: The role of parenteral nutrition (PN) therapy as an independent risk
      factor for central venous catheter (CVC)-related infection in nonselected adult
      patients is not well established. The aim of this study was to evaluate PN as a
      risk factor for central venous catheter-related infection in nonselected adult
      patients in a general university hospital. METHODS: Patients using central venous
      catheters, exposed or nonexposed to PN, were prospectively followed for
      development of central venous catheter-related infection. RESULTS: One hundred
      fifty-three patients were studied; 28 developed central venous catheter-related
      infection. Patients with central venous catheter-related infection presented
      higher frequency of PN use than patients without infection (60.7 vs 34.4%; p =
      .010). Multivariate Cox analysis showed that PN (relative risk (RR) = 3.30; 95%
      confidence interval [CI], 1.30-8.34; p = .012) was the only risk factor for
      central venous catheter-related infection. Malnutrition (RR = 0.45; 95% CI, 0.15
      1.34; p = .152), days of hospitalization before central venous catheter insertion
      (RR = 1.00; 95% CI, 0.98-1.02; p = .801), and sustained hyperglycemia (RR = 0.49;
      95% CI, 0.98-1.21; p = .091) were not significant in the model. Multiple logistic
      regression revealed that mal-nutrition (odds ratio [OR] = 8.05; 95% CI, 1.85
      35.03; p = .005), central venous catheter indication for surgical-related
      pathology (OR = 7.26; 95% CI, 2.51-21.04; p < .001), sustained hyperglycemia (OR
      = 4.34; 95% CI, 1.79-10.52; p = .001), and days of hospitalization before central
      venous catheter insertion (OR = 1.04; 95% CI, 1.01-1.07; p = .004) were
      associated with PN use after adjustment for Assessment Score Intervention System
      score (OR = 0.33; 95% CI, 0.14-0.80; p = .014). CONCLUSIONS: PN therapy is an
      independent risk factor for central venous catheter-related infection in
      nonselected hospitalized adult patients.

PMID- 16107601
TI  - Improved care and reduced costs for patients requiring peripherally inserted
      central catheters: the role of bedside ultrasound and a dedicated team.
AB  - BACKGROUND: We conducted a prospective quality assurance (QA) study to determine
      if a team dedicated to placing peripherally inserted central catheters (PICCs)
      would improve patient care and reduce costs. METHODS: In April 2000, a dedicated
      team of physicians, physician assistants, nurses, and interventional radiologists
      (IR) was established to coordinate and approve all PICC placements at our
      hospital. Ultrasound (US) became available in November 2000 to assist with
      bedside PICC placement. A QA database was created allowing data from 3 time
      periods reflecting initiation of the PICC service (April-June 2000), initial
      implementation of bedside US-guided PICC placement (October-December 2000), and
      the current service (October-December 2002) to be analyzed and compared. RESULTS:
      For all time periods analyzed, the PICC team found that one-third of PICC
      requests was inappropriate and, therefore, disapproved placement. With addition
      of US, the bedside PICC placement rate increased to 94% compared with 73% at
      service initiation. This was associated with an overall 80% decrease in average
      patient waiting time for a PICC, facilitating more timely discharges from the
      hospital. Finally, placement costs were reduced by 9% six months after initiation
      of our service and by 24% after US became available. CONCLUSIONS: A dedicated
      PICC team improves patient care by preventing inappropriate PICC placements and
      decreasing patient waiting times. A PICC team with US capability also reduces
      costs by minimizing expensive use of IR facilities and reducing hospital lengths
      of stay. A dedicated PICC service should become the standard of care for all
      hospitals with high-volume PICC use.

PMID- 16107602
TI  - Effects of hypercaloric feeding on nutrition status and carbon dioxide production
      in patients with long-term mechanical ventilation.
AB  - BACKGROUND: To clarify clinical arguments regarding nutrition support in patients
      with long-term mechanical ventilation, we investigated the effects of
      hypercaloric feeding on nutrition status and carbon dioxide production. METHODS:
      Twenty-eight mechanically ventilated, clinically stable patients with nasogastric
      tube feeding were recruited and randomly divided into the control and
      hypercaloric groups, which were provided with 1.2- and 1.8-fold of resting energy
      expenditure (REE), respectively. The arterial and venous blood samples were
      collected, the anthropometric measurements were determined, the serum
      concentrations of nutrition-related proteins were measured, and the parameters on
      the ventilator and indirect calorimeter were recorded on weeks 0, 2, and 4.
      RESULTS: There were no significant changes in anthropometric measurements, blood
      gas tensions, and REE between the control and hypercaloric groups during the
      experimental period (mixed model with repeated measures analysis, p < .05). After
      adjusted for values on week 0 and time, patients with hypercaloric feeding had
      significantly increased levels in white blood cells, hemoglobin, and hematocrit.
      However, the control group had significantly decreased and the hypercaloric group
      had significantly increased serum concentrations of prealbumin and transferrin,
      rate of carbon dioxide production, and respiratory quotient (RQ) from week 0 to
      week 4. CONCLUSION: Our results suggest that 4 weeks of hypercaloric feeding may
      significantly increase the production of carbon dioxide but may not significantly
      alter the clinical outcomes in patients with long-term mechanical ventilation.
      The adverse effects of hypercaloric feeding may easily be overlooked, and the
      appropriateness of nutrition support should be carefully monitored in patients
      with mechanical ventilation.

PMID- 16107603
TI  - Do pH and temperature play a role in gastrostomy tube deterioration?
AB  - The effects of pH and temperature over time on percutaneous endoscopic
      gastrostomy (PEG) tube longevity were examined in an in vitro model. Two sets of
      tubes were obtained from 7 major US PEG manufacturers. Using scissors, each PEG
      tube was cut cross-sectionally 8 cm from the bumper end of the tube. Both
      qualitative (photographs) and quantitative (mass) measurements were taken at
      baseline. Median physiologic gastric acidity was approximated by completely
      submerging 1 set of each cut PEG tube in a 250-mL glass jar containing a 0.050-N
      (pH 1.3) solution of hydrochloric acid. As a control, another set of each PEG
      tube was completely submerged in a 250-mL glass jar containing a buffer solution
      of pH 6. Each jar was then submerged in the waterbath so that the water
      completely covered the tube but did not enter the jar. The waterbath was covered
      and maintained at a constant temperature of 37 degrees C. Measurements taken at
      baseline were repeated at 168 days and again at 375 days. On qualitative
      examination, no dilations, brittleness, obstruction, nodularity, tears, loss of
      elasticity, color changes, tube fracturing, kinking, loss of resilience, or
      variation in external diameter was observed. Quantitative examination showed no
      change in mass. Tubes removed from the pH 1.3 solution appeared identical to the
      tubes removed from the pH 6 solution. In all cases, there were no apparent
      changes from baseline. These findings suggest that temperature and pH can be
      excluded as predominant factors in tube deterioration and lend further support to
      a microbial hypothesis of PEG tube deterioration.

PMID- 16107604
TI  - Do individual nutrients affect gene expression?

PMID- 16107605
TI  - Is there cognitive decline 1 year after CABG? Comparison with surgical and
      nonsurgical controls.
AB  - BACKGROUND: It is widely assumed that decline in cognition after coronary artery
      bypass grafting (CABG) is related to use of the cardiopulmonary bypass pump.
      Because most studies have not included comparable control groups, it remains
      unclear whether postoperative cognitive changes are specific to cardiopulmonary
      bypass, general aspects of surgery, or vascular pathologies of the aging brain.
      METHODS: This nonrandomized study included four groups: CABG patients (n = 140);
      off-pump coronary surgery (n = 72); nonsurgical cardiac controls (NSCC) with
      diagnosed coronary artery disease but no surgery (n = 99); and heart healthy
      controls (HHC) with no cardiac risk factors (n = 69). Subjects were evaluated at
      baseline (preoperatively), 3 months, and 12 months. Eight cognitive domains and a
      global cognitive score, as well as depressive and subjective symptoms were
      analyzed. RESULTS: At baseline, patients with coronary artery disease (CABG, off
      pump, and NSCC) had lower performance than the HHC group in several cognitive
      domains. By 3 months, all groups had improved. From 3 to 12 months, there were
      minimal intrasubject changes for all groups. No consistent differences between
      the CABG and off-pump patients were observed. CONCLUSIONS: Compared with heart
      healthy controls (HHC), the groups with coronary artery disease had lower
      cognitive test scores at baseline. There was no evidence that the cognitive test
      performance of coronary artery bypass grafting (CABG) patients differed from that
      of control groups with coronary artery disease over a 1-year period. This study
      emphasizes the need for appropriate control groups for interpreting longitudinal
      changes in cognitive performance after CABG.

PMID- 16107606
TI  - Seminal DNase frees spermatozoa entangled in neutrophil extracellular traps.
AB  - Insemination always stimulates neutrophil migration into the female reproductive
      tract (FRT), which eliminates excess spermatozoa and bacterial contaminants
      introduced by the breeding process. However, the presence of neutrophils in the
      FRT at the time of semen deposition has been shown to result in sperm-neutrophil
      binding that reduces motility and fertility. Although the binding and trapping
      mechanism has not been determined, seminal plasma (SP) was found to include a
      protein factor or factors that reduced sperm-neutrophil binding and improved
      fertility of sperm inseminated in the presence of neutrophils. Although DNase has
      been shown to be present in the SP of different species and has been associated
      with improved fertility in bulls, the mechanism(s) explaining this association
      and the paradox of DNA-packed cells being associated with DNase have remained
      unresolved. We demonstrate that sperm-activated neutrophils extrude their DNA,
      which in turn traps sperm cells and hinders their motility (and ultimately may
      hinder sperm transport to the fertilization site). DNase activity present in the
      SP digests the extruded DNA and frees entangled spermatozoa, which in turn may
      allow more spermatozoa to reach the oviduct, and explains at least one mechanism
      by which SP increases the rate of fertility. The ability of SP proteins to
      suppress neutrophil activation in the presence of spermatozoa did not render
      neutrophils incapable of combating bacteria, demonstrating that SP proteins are
      highly selective for suppressing neutrophils activated by spermatozoa, but not by
      bacteria.

PMID- 16107607
TI  - Catsper3 and catsper4 encode two cation channel-like proteins exclusively
      expressed in the testis.
AB  - CATSPER1 and CATSPER2 are two cation channel-like proteins exclusively expressed
      in the testis and essential for normal sperm motility and male fertility. Using
      in silico subtraction and database mining, we identified expressed sequence tags
      encoding two previously uncharacterized cation channel-like proteins structurally
      homologous to CATSPER1 and CATSPER2. Similar to CATSPER1 and CATSPER2, these two
      proteins contain a single-ion transport domain comprised of six transmembrane
      spanning regions, in which the fourth transmembrane region resembles a voltage
      sensor and a pore-forming region lies between transmembrane regions 5 and 6. The
      pore contains the consensus sequence T x D x W, which is indicative of a
      potential calcium-selective channel. The mRNAs for Catsper3 and Catsper4 were
      detected exclusively in the testis using multitissue Northern blot and RT-PCR
      analyses. The onsets of both genes coincide with the first appearance of
      spermatids during testicular development. In situ hybridization analyses revealed
      that Catsper3 and Catsper4 mRNAs displayed identical localization patterns and
      were confined to spermatids of steps 1-8. Immunofluorescence and
      immunohistochemistry analyses demonstrated that these two proteins were expressed
      within the acrosome of late spermatids and spermatozoa. Our data suggest that
      CATSPER3 and CATSPER4 are two cation-channel proteins and have roles in acrosome
      reaction and male fertility.

PMID- 16107608
TI  - Whole-cell electrophysiology of gonadotropin-releasing hormone neurons that
      express green fluorescent protein in the terminal nerve of transgenic medaka
      (Oryzias latipes).
AB  - Gonadotropin-releasing hormone (GnRH) controls reproduction in vertebrates. Most
      studies have focused on the population of GnRH neurons in the hypothalamus that
      ultimately controls gonadal function. However, all vertebrates studied to date
      have two to three anatomically distinct populations of GnRH neurons that express
      different forms of this hormone. The purpose of the present study was to develop
      a new model for studying the population of GnRH neurons in the terminal nerve
      (TN) associated with the olfactory bulb and then to characterize their pattern of
      action potential firing to provide a foundation for understanding the role of
      these neurons in regulating reproduction. A stable line of transgenic medaka
      (Oryzias latipes) was generated in which a DNA construct containing the salmon
      GnRH (Gnrh3) promoter linked to green fluorescent protein (GFP) was expressed in
      TN-GnRH3 neurons. This population of GnRH neurons is located at or near the
      ventral surface of the brain, making them ideally situated for
      electrophysiological analysis. Whole-cell and loose-patch recordings in current
      clamp mode were performed on these neurons from excised, intact brains of adult
      males in which afferent and efferent neural connections remained intact. All TN
      GnRH3-GFP neurons that we recorded showed a beating pattern of spontaneous action
      potential firing. Action potentials were blocked by tetrodotoxin, indicating they
      are generated by a voltage-sensitive Na+ current; however, an oscillation in
      subthreshold membrane potential persisted. The present results indicate that this
      transgenic fish will provide an excellent model for studying the cell physiology
      of an extrahypothalamic population of GnRH neurons.

PMID- 16107609
TI  - Analysis of flagellar bending in hamster spermatozoa: characterization of an
      effective stroke.
AB  - The mechanism by which flagella generate the propulsive force for movement of
      hamster spermatozoa was analyzed quantitatively. Tracing points positioned 30,
      60, 90, and 120 microm from the head-midpiece junction on the flagellum revealed
      that they all had zigzag trajectories. These points departed from and returned to
      the line that crossed the direction of progression. They moved along the concave
      side (but not the convex side) of the flagellar envelope that was drawn by
      tracing the trajectory of the entire flagellum. To clarify this asymmetry, the
      bending rate was analyzed by measuring the curvatures of points 30, 60, 90, and
      120 microm from the head-midpiece junction. The bending rate was not constant
      through the cycle of flagellar bending. The rate was higher when bending was in
      the direction described by the curve of the hook-shaped head (defined as a
      principal bend [P-bend]) to the opposite side (R-bend). We measured a lower
      bending rate in the principal direction (R-bend to P-bend). To identify the point
      at which the propulsive force is generated efficiently within the cycle of
      flagellar bending, we calculated the propulsive force generated at each point on
      the flagellum. The value of the propulsive force was positive whenever the
      flagellum bent from an R-bend to a P-bend (when the bending rate was lowest). By
      contrast, the propulsive force value was zero or negative when the flagellum bent
      in the other direction (when the bending rate was higher). These results indicate
      that flagellar bending in hamster spermatozoa produces alternate effective and
      ineffective strokes during propulsion.

PMID- 16107610
TI  - Impairment of decidualization in SRC-deficient mice.
AB  - Many signaling events induced by ovarian steroid hormones, cytokines, and growth
      factors are involved in the process of decidualization of human and rodent
      endometrium. We have reported previously that tyrosine kinase activation of SRC
      functionally participates in decidualization of human endometrial stromal cells.
      To address its essential role in decidualization, we examined, using wild-type
      and Src knockout mice, whether the process of decidualization was impaired in the
      absence of SRC. Immunohistochemistry using an antibody specific for the active
      form of SRC revealed that the active SRC was expressed prominently in the
      decidualizing stromal cells of the pregnant wild-type mouse. Moreover, the active
      SRC was upregulated in the uterine horn with artificially stimulated decidual
      reaction. In comparison with wild-type and Src heterozygous mice, the uterus of
      Src null mice showed no apparent decidual response following artificial
      stimulation. Ovarian steroid-induced decidualization in vitro, as determined by
      morphological changes and expression of decidual/trophoblast prolactin-related
      protein and prostaglandin-endoperoxide synthase 2 (also known as Cox2), both of
      which are decidualization markers, did not occur in a timely fashion in
      endometrial stromal cells isolated from the uteri of SRC-deficient mice compared
      to those from wild-type and Src heterozygous mice. Our results collectively
      suggest that SRC is an indispensable signaling component for maximal
      decidualization in mice.

PMID- 16107611
TI  - The beneficial effects of insulin and metformin on in vitro developmental
      potential of porcine oocytes and embryos.
AB  - To investigate whether insulin and/or metformin improve the developmental
      competence of porcine oocytes and embryos, insulin (100 ng/ml) and/or metformin
      (10(-5) M) were supplemented during in vitro maturation (IVM) and/or in vitro
      culture (IVC) periods. Insulin (33 to 34% vs. 21%) or insulin plus metformin (27
      to 39% vs. 21%) significantly (P < 0.01) increased the rates of blastocyst
      formation, whereas metformin alone had no effect when added during the first half
      (0-22 h), the latter half (22-44 h), or the entire (0-44 h) maturation period. No
      additional effect of insulin plus metformin on increasing blastocyst formation
      was observed compared to insulin alone. When supplemented during IVC, insulin
      (34% vs. 23%) or insulin plus metformin (35% vs. 23%) significantly (P < 0.05)
      increased the rates of blastocyst formation, whereas metformin alone had no
      effect. Compared to insulin alone, no additional effect of insulin plus metformin
      on increasing blastocyst formation was observed. When added during the entire IVM
      and IVC, insulin (40% vs. 24%) or insulin plus metformin (52% vs. 21%)
      significantly increased the rates of blastocyst formation, whereas metformin
      alone had no effect. In addition, the effect of insulin was enhanced when
      supplemented with metformin compared to insulin alone (52% vs. 40%). After IVM,
      oocyte glutathione (GSH) content and tyrosine kinase activity were measured.
      Insulin significantly (P < 0.01) increased oocyte GSH content (6.2 pmol vs. 4.3
      pmol) and metformin significantly (P < 0.01) enhanced the action of insulin on
      GSH content (7.3 pmol vs. 6.2 pmol) and tyrosine kinase activity (1.9 arbitrary
      units [AU] vs. 1.5 AU) when compared to insulin alone. In conclusion, insulin
      increased the developmental potential of porcine oocytes and embryos, and
      metformin enhanced the action of insulin when supplemented during the entire IVM
      and IVC. The effects of insulin and metformin were associated with oocyte GSH
      content and tyrosine kinase activity.

PMID- 16107612
TI  - The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis.
AB  - PTEN is an important tumor suppressor gene. Hereditary mutation of PTEN causes
      tumor-susceptibility diseases such as Cowden disease. We used the Cre-loxP system
      to generate an endothelial cell-specific mutation of Pten (Tie2CrePten) in mice.
      Tie2CrePten(flox/+) mice displayed enhanced tumorigenesis due to an increase in
      angiogenesis driven by vascular growth factors. This effect was partially
      dependent on the PI3K subunits p85alpha and p110gamma. In vitro,
      Tie2CrePten(flox/+) endothelial cells showed enhanced proliferation/migration.
      Tie2CrePten(flox/flox) mice died before embryonic day 11.5 (E11.5) due to
      bleeding and cardiac failure caused by impaired recruitment of pericytes and
      vascular smooth muscle cells to blood vessels, and of cardiomyocytes to the
      endocardium. These phenotypes depend strongly on p110gamma rather than on
      p85alpha and were associated with decreased expression of Ang-1, VCAM-1, connexin
      40, and ephrinB2 but increased expression of Ang-2, VEGF-A, VEGFR1, and VEGFR2.
      Pten is thus indispensable for normal cardiovascular morphogenesis and post-natal
      angiogenesis, including tumor angiogenesis.

PMID- 16107613
TI  - RhoC is dispensable for embryogenesis and tumor initiation but essential for
      metastasis.
AB  - The Rho proteins are Ras-related guanosine triphosphatases (GTPases) that
      function in cytoskeletal reorganization, cell migration, and stress fiber and
      focal adhesion formation. Overexpression of RhoC enhances the ability of melanoma
      cells to exit the blood and colonize the lungs. However, in vivo confirmation of
      RhoC's role in metastasis has awaited a RhoC-deficient mouse model. Here we
      report the generation of RhoC-deficient mice and show that RhoC is dispensable
      for embryonic and post-natal development. We demonstrate that loss of RhoC does
      not affect tumor development but decreases tumor cell motility and metastatic
      cell survival leading to a drastic inhibition of metastasis.

PMID- 16107614
TI  - State-dependent Ras signaling and AMPA receptor trafficking.
AB  - Synaptic trafficking of AMPA-Rs, controlled by small GTPase Ras signaling, plays
      a key role in synaptic plasticity. However, how Ras signals synaptic AMPA-R
      trafficking is unknown. Here we show that low levels of Ras activity stimulate
      extracellular signal-regulated kinase kinase (MEK)-p42/44 MAPK (extracellular
      signal-regulated kinase [ERK]) signaling, whereas high levels of Ras activity
      stimulate additional Pi3 kinase (Pi3K)-protein kinase B (PKB) signaling, each
      accounting for approximately 50% of the potentiation during long-term
      potentiation (LTP). Spontaneous neural activity stimulates the Ras-MEK-ERK
      pathway that drives GluR2L into synapses. In the presence of neuromodulator
      agonists, neural activity also stimulates the Ras-Pi3K-PKB pathway that drives
      GluR1 into synapses. Neuromodulator release increases with increases of
      vigilance. Correspondingly, Ras-MEK-ERK activity in sleeping animals is
      sufficient to deliver GluR2L into synapses, while additional increased Ras-Pi3K
      PKB activity in awake animals delivers GluR1 into synapses. Thus, state-dependent
      Ras signaling, which specifies downstream MEK-ERK and Pi3K-PKB pathways,
      differentially control GluR2L- and GluR1-dependent synaptic plasticity.

PMID- 16107615
TI  - p63 deficiency activates a program of cellular senescence and leads to
      accelerated aging.
AB  - The p53 tumor suppressor plays a key role in organismal aging. A cellular
      mechanism postulated to drive the aging process is cellular senescence, mediated
      in part by p53. Although senescent cells accumulate in elderly individuals, most
      studies have relied on correlating in vitro senescence assays with in vivo
      phenotypes of aging. Here, using two different mouse models in which the p53
      related protein p63 is compromised, we demonstrate that cellular senescence and
      organismal aging are intimately linked and that these processes are mediated by
      p63 loss. We found that p63(+/-) mice have a shortened life span and display
      features of accelerated aging. Both germline and somatically induced p63
      deficiency activates widespread cellular senescence with enhanced expression of
      senescent markers SA-beta-gal, PML, and p16(INK4a). Using an inducible tissue
      specific p63 conditional model, we further show that p63 deficiency induces
      cellular senescence and causes accelerated aging phenotypes in the adult. Our
      results thus suggest a causative link between cellular senescence and aging in
      vivo, and demonstrate that p63 deficiency accelerates this process.

PMID- 16107616
TI  - Molecular mechanism of temperature sensing by the circadian clock of Neurospora
      crassa.
AB  - Expression levels and ratios of the long (l) and short (s) isoforms of the
      Neurospora circadian clock protein FREQUENCY (FRQ) are crucial for temperature
      compensation of circadian rhythms. We show that the ratio of l-FRQ versus s-FRQ
      is regulated by thermosensitive splicing of intron 6 of frq, a process removing
      the translation initiation site of l-FRQ. Thermosensitivity is due to inefficient
      recognition of nonconsensus splice sites at elevated temperature. The temperature
      dependent accumulation of FRQ relative to bulk protein is controlled at the level
      of translation. The 5'-UTR of frq RNA contains six upstream open reading frames
      (uORFs) that are in nonconsensus context for translation initiation.
      Thermosensitive trapping of scanning ribosomes at the uORFs leads to reduced
      translation of the main ORF and allows adjustment of FRQ levels according to
      ambient temperature.

PMID- 16107617
TI  - Images in clinical medicine. Central serous chorioretinopathy in pregnancy.

PMID- 16107618
TI  - Naked.

PMID- 16107619
TI  - Medical marijuana and the Supreme Court.

PMID- 16107620
TI  - Sex and racial differences in the management of acute myocardial infarction, 1994
      through 2002.
AB  - BACKGROUND: Although increased attention has been paid to sex and racial
      differences in the management of myocardial infarction, it is unknown whether
      these differences have narrowed over time. METHODS: With the use of data from the
      National Registry of Myocardial Infarction, we examined sex and racial
      differences in the treatment of patients who were deemed to be "ideal candidates"
      for particular treatments and in deaths among 598,911 patients hospitalized with
      myocardial infarction between 1994 and 2002. RESULTS: In the unadjusted analysis,
      sex and racial differences were observed for rates of reperfusion therapy (for
      white men, white women, black men, and black women: 86.5, 83.3, 80.4, and 77.8
      percent, respectively; P<0.001), use of aspirin (84.4, 78.7, 83.7, and 78.4
      percent, respectively; P<0.001), use of beta-blockers (66.6, 62.9, 67.8, and 64.5
      percent; P<0.001), and coronary angiography (69.1, 55.9, 64.0, and 55.0 percent;
      P<0.001). After multivariable adjustment, racial and sex differences persisted
      for rates of reperfusion therapy (risk ratio for white women, black men, and
      black women: 0.97, 0.91, and 0.89, respectively, as compared with white men) and
      coronary angiography (relative risk, 0.91, 0.82, and 0.76) but were attenuated
      for the use of aspirin (risk ratio, 0.97, 0.98, and 0.94) and beta-blockers (risk
      ratio, 0.98, 1.00, and 0.96); all risks were unchanged over time. Adjusted in
      hospital mortality was similar among white women (risk ratio, 1.05; 95 percent
      confidence interval, 1.03 to 1.07) and black men (risk ratio, 0.95; 95 percent
      confidence interval, 0.89 to 1.00), as compared with white men, but was higher
      among black women (risk ratio, 1.11; 95 percent confidence interval, 1.06 to
      1.16) and was unchanged over time. CONCLUSIONS: Rates of reperfusion therapy,
      coronary angiography, and in-hospital death after myocardial infarction, but not
      the use of aspirin and beta-blockers, vary according to race and sex, with no
      evidence that the differences have narrowed in recent years.

PMID- 16107621
TI  - Racial trends in the use of major procedures among the elderly.
AB  - BACKGROUND: Differences in the use of major procedures according to patients'
      race are well known. Whether national and local initiatives to reduce these
      differences have been successful is unknown. METHODS: We examined data for men
      and women enrolled in Medicare from 1992 through 2001 on annual age-standardized
      rates of receipt of nine surgical procedures previously shown to have disparities
      in the rates at which they were performed in black patients and in white
      patients. We also examined data according to hospital-referral region for three
      of the nine procedures: coronary-artery bypass grafting (CABG), carotid
      endarterectomy, and total hip replacement. RESULTS: Nationally, in 1992, the
      rates of receipt for all the procedures examined were higher among white patients
      than among black patients. The difference between the rates among whites and
      blacks increased significantly between 1992 and 2001 for five of the nine
      procedures, remained unchanged for three procedures, and narrowed significantly
      for one procedure. We examined rates of CABG, carotid endarterectomy, and total
      hip replacement in 158 hospital-referral regions (79 hospital-referral regions
      for black men and white men and 79 for black women and white women) with an
      adequate number of persons for each procedure. We found that in the early 1990s,
      whites had higher rates for these procedures than blacks in every hospital
      referral region. By 2001, the difference between whites and blacks (both men and
      women) in the rates of these procedures narrowed significantly in 22 hospital
      referral regions, widened significantly in 42, and were not significantly changed
      in the remaining hospital-referral regions. At the end of the study period, we
      found no hospital-referral region in which the difference in rates between whites
      and blacks was eliminated for men or women with regard to any of these three
      procedures. CONCLUSIONS: For the decade of the 1990s, we found no evidence,
      either nationally or locally, that efforts to eliminate racial disparities in the
      use of high-cost surgical procedures were successful.

PMID- 16107622
TI  - Trends in the quality of care and racial disparities in Medicare managed care.
AB  - BACKGROUND: Since 1997, all managed-care plans administered by Medicare have
      reported on quality-of-care measures from the Health Plan Employer Data and
      Information Set (HEDIS). Studies of early data found that blacks received care
      that was of lower quality than that received by whites. In this study, we
      assessed changes over time in the overall quality of care and in the magnitude of
      racial disparities in nine measures of clinical performance. METHODS: In order to
      compare the quality of care for elderly white and black beneficiaries enrolled in
      Medicare managed-care plans who were eligible for at least one of nine HEDIS
      measures, we analyzed 1.8 million individual-level observations from 183 health
      plans from 1997 to 2003. For each measure, we assessed whether the magnitude of
      the racial disparity had changed over time with the use of multivariable models
      that adjusted for the age, sex, health plan, Medicaid eligibility, and
      socioeconomic position of beneficiaries on the basis of their area of residence.
      RESULTS: During the seven-year study period, clinical performance improved on all
      measures for both white enrollees and black enrollees (P<0.001). The gap between
      white beneficiaries and black beneficiaries narrowed for seven HEDIS measures
      (P<0.01). However, racial disparities did not decrease for glucose control among
      patients with diabetes (increasing from 4 percent to 7 percent, P<0.001) or for
      cholesterol control among patients with cardiovascular disorders (increasing from
      14 percent to 17 percent; change not significant, P=0.72). CONCLUSIONS: The
      measured quality of care for elderly Medicare beneficiaries in managed-care plans
      improved substantially from 1997 to 2003. Racial disparities declined for most,
      but not all, HEDIS measures we studied. Future research should examine factors
      that contributed to the narrowing of racial disparities on some measures and
      focus on interventions to eliminate persistent disparities in the quality of
      care.

PMID- 16107623
TI  - Soft-tissue sarcomas in adults.

PMID- 16107624
TI  - Images in clinical medicine. Four artificial heart valves.

PMID- 16107625
TI  - Case records of the Massachusetts General Hospital. Case 25-2005. A 40-year-old
      man with prolonged fever and weight loss.

PMID- 16107626
TI  - Health disparities--less talk, more action.

PMID- 16107627
TI  - Nitric oxide-eluting polyurethanes--vascular grafts of the future?

PMID- 16107628
TI  - Exhaled nitric oxide and asthma.

PMID- 16107629
TI  - Heart-rate profile during exercise as a predictor of sudden death.

PMID- 16107630
TI  - Coronary-artery bypass grafting versus stent implantation.

PMID- 16107631
TI  - Circulating osteoblast-lineage cells.

PMID- 16107632
TI  - Asthma and invasive pneumococcal disease.

PMID- 16107633
TI  - Response of a nonmalignant pleural effusion to bevacizumab.

PMID- 16107634
TI  - Cerebral folate deficiency syndrome.

PMID- 16107635
TI  - Strong effects of subphysiological temperature on the function and plasticity of
      mammalian presynaptic terminals.
AB  - Most cellular processes are known to be strongly temperature dependent.
      Nevertheless, a large fraction of studies of mammalian synaptic function have
      been and are performed near room temperature (i.e., at least 10 degrees C below
      physiological temperature). Here, we examined the effects of temperature on
      presynaptic function in primary cultures of rat hippocampal neurons. FM dyes,
      VAMP (vesicle-associated membrane protein)-GFP (green fluorescent protein)
      transfection, and HRP uptake were used to quantify various aspects of synaptic
      vesicle recycling. Our results show that there are very substantial differences
      in synaptic vesicle recycling at physiological temperature as opposed to the
      common, lower experimental temperatures. At 37 degrees C, compared with 23
      degrees C, the speed of both exocytosis and endocytosis was higher. The size of
      the recycling vesicle pool (in both number of vesicles and spatial extent) was
      twofold larger at 37 degrees C. In addition, although repeated 10 Hz electrical
      stimulation caused an NMDA receptor-dependent enlargement (averaging 170%) of the
      measurable recycling vesicle pool at 23 degrees C, the same stimulus repetition
      had no effect at 37 degrees C. These results show that it is potentially
      misleading to extend conclusions drawn about vesicle function or presynaptic
      plasticity at lowered experimental temperature to physiological conditions and
      that much new experimental work at the higher physiological temperature range
      will be needed to understand the true parameters of presynaptic functions.

PMID- 16107636
TI  - Feedforward inhibitory control of sensory information in higher-order thalamic
      nuclei.
AB  - Sensory stimuli evoke strong responses in thalamic relay cells, which ensure a
      faithful relay of information to the neocortex. However, relay cells of the
      posterior thalamic nuclear group in rodents, despite receiving significant
      trigeminal input, respond poorly to vibrissa deflection. Here we show that
      sensory transmission in this nucleus is impeded by fast feedforward inhibition
      mediated by GABAergic neurons of the zona incerta. Intracellular recordings of
      posterior group neurons revealed that the first synaptic event after whisker
      deflection is a prominent inhibition. Whisker-evoked EPSPs with fast rise time
      and longer onset latency are unveiled only after lesioning the zona incerta.
      Excitation survives barrel cortex lesion, demonstrating its peripheral origin.
      Electron microscopic data confirm that trigeminal axons make large synaptic
      terminals on the proximal dendrites of posterior group cells and on the somata of
      incertal neurons. Thus, the connectivity of the system allows an unusual
      situation in which inhibition precedes ascending excitation resulting in
      efficient shunting of the responses. The dominance of inhibition over excitation
      strongly suggests that the paralemniscal pathway is not designed to relay inputs
      triggered by passive whisker deflection. Instead, we propose that this pathway
      operates through disinhibition, and that the posterior group forwards to the
      cerebral cortex sensory information that is contingent on motor instructions.

PMID- 16107637
TI  - Glycine receptors in CNS neurons as a target for nonretrograde action of
      cannabinoids.
AB  - At many central synapses, endocannabinoids released by postsynaptic cells act
      retrogradely on presynaptic G-protein-coupled cannabinoid receptors to inhibit
      neurotransmitter release. Here, we demonstrate that cannabinoids may directly
      affect the functioning of inhibitory glycine receptor (GlyR) channels. In
      isolated hippocampal pyramidal and Purkinje cerebellar neurons, endogenous
      cannabinoids anandamide and 2-arachidonylglycerol, applied at physiological
      concentrations, inhibited the amplitude and altered the kinetics of rise time,
      desensitization, and deactivation of the glycine-activated current (I(Gly)) in a
      concentration-dependent manner. These effects of cannabinoids were observed in
      the presence of cannabinoid CB1/CB3, vanilloid receptor 1 antagonists, and the G
      protein inhibitor GDPbetaS, suggesting a direct action of cannabinoids on GlyRs.
      The effect of cannabinoids on I(Gly) desensitization was strongly voltage
      dependent. We also demonstrate that, in the presence of a GABA(A) receptor
      antagonist, GlyRs may contribute to the generation of seizure-like activity
      induced by short bursts (seven stimuli) of high-frequency stimulation of inputs
      to hippocampal CA1 region, because this activity was diminished by selective GlyR
      antagonists (strychnine and ginkgolides B and J). The GlyR-mediated rhythmic
      activity was also reduced by cannabinoids (anandamide) in the presence of a CB1
      receptor antagonist. These results suggest that the direct inhibition of GlyRs by
      endocannabinoids can modulate the hippocampal network activity.

PMID- 16107638
TI  - Experiential effects of appetitive and nonappetitive odors on feeding behavior in
      the blowfly, Phormia regina: a putative role for tyramine in appetite regulation.
AB  - In humans, appetite is affected by food experiences and food flavors. In the
      blowfly Phormia regina, we found that feeding threshold to sugar increased in the
      presence of the odor of D-limonene and decreased in the presence of the odor of
      dithiothreitol (DTT). Using these odors as representative nonappetitive and
      appetitive flavors, we demonstrated the role played by tyramine (TA) in appetite
      regulation by experiences of food flavors. When fed with sucrose flavored with D
      limonene for 5 d after emergence, flies showed subsequent decreased appetite to
      plain sucrose, whereas when they were fed with sucrose flavored by DTT they
      showed increased appetite. However, mushroom body (MB)-ablated flies did not show
      these patterns. This suggests that MB, one of the primary memory centers of the
      insect brain, is necessary for the flies to apply previous experiences of food
      flavors to appetitive learning behaviors. In addition, flies' previously acquired
      decreased or increased appetites showed parallel changes with both octopamine
      (OA) and tyramine levels in the brain. However, injection experiments with OA,
      TA, or their agonist and antagonist indicated that TA more directly mediates
      feeding threshold determination, which was affected by acquired memories of food
      flavors.

PMID- 16107639
TI  - The two isoforms of the Caenorhabditis elegans leukocyte-common antigen related
      receptor tyrosine phosphatase PTP-3 function independently in axon guidance and
      synapse formation.
AB  - Leukocyte-common antigen related (LAR)-like phosphatase receptors are conserved
      cell adhesion molecules that function in multiple developmental processes. The
      Caenorhabditis elegans ptp-3 gene encodes two LAR family isoforms that differ in
      the extracellular domain. We show here that the long isoform, PTP-3A, localizes
      specifically at synapses and that the short isoform, PTP-3B, is extrasynaptic.
      Mutations in ptp-3 cause defects in axon guidance that can be rescued by PTP-3B
      but not by PTP-3A. Mutations that specifically affect ptp-3A do not affect axon
      guidance but instead cause alterations in synapse morphology. Genetic double
      mutant analysis is consistent with ptp-3A acting with the extracellular matrix
      component nidogen, nid-1, and the intracellular adaptor alpha-liprin, syd-2. nid
      1 and syd-2 are required for the recruitment and stability of PTP-3A at synapses,
      and mutations in ptp-3 or nid-1 result in aberrant localization of SYD-2.
      Overexpression of PTP-3A is able to bypass the requirement for nid-1 for the
      localization of SYD-2 and RIM. We propose that PTP-3A acts as a molecular link
      between the extracellular matrix and alpha-liprin during synaptogenesis.

PMID- 16107640
TI  - Reliability of signal transfer at a tonically transmitting, graded potential
      synapse of the locust ocellar pathway.
AB  - We assessed the performance of a synapse that transmits small, sustained, graded
      potentials between two classes of second-order ocellar "L-neurons" of the locust.
      We characterized the transmission of both fixed levels of membrane potential and
      fluctuating signals by recording postsynaptic responses to changes in presynaptic
      potential. To ensure repeatability between stimuli, we controlled presynaptic
      signals with a voltage clamp. We found that the synapse introduces noise above
      the level of background activity in the postsynaptic neuron. By driving the
      presynaptic neuron with slow-ramp changes in potential, we found that the number
      of discrete signal levels the synapse transmits is approximately 20. It can also
      transmit approximately 20 discrete levels when the presynaptic signal is a graded
      rebound spike. Synaptic noise level is constant over the operating range of the
      synapse, which would not be expected if presynaptic potential set the probability
      for the release of individual quanta of neurotransmitter according to Poisson
      statistics. Responses to individual quanta of neurotransmission could not be
      resolved, which is consistent with a synapse that operates with large numbers of
      vesicles evoking small responses. When challenged with white noise stimuli, the
      synapse can transmit information at rates up to 450 bits/s, a performance that is
      sufficient to transmit natural signals about changes in illumination.

PMID- 16107641
TI  - High-concentration rapid transients of glutamate mediate neural-glial
      communication via ectopic release.
AB  - Until recently, communication from neurons to astrocytes was thought to be
      mediated by low-concentration transients of glutamate caused by spillover from
      the synaptic cleft. However, quantal events recorded in rat cerebellar Bergmann
      glial cells (BGs) have fast kinetics, comparable with those recorded in neurons.
      By combining outside-out patch recordings of BG AMPA receptors and quantitative
      electron microscopic analysis of glutamate receptor subunit 1 (GluR1) and GluR4
      immunogold labeling measurements, at both the soma and membranes surrounding
      synapses, we estimate the absolute density of functional AMPA receptors. Using a
      kinetic model of BG AMPA receptors, we find that quantal events recorded in BGs
      are produced by high-concentration (approximately 1-1.5 mM), fast transients
      (approximately 0.5 ms decay) of glutamate, similar to transients within the
      synaptic cleft. Our results indicate that neural signaling to BGs is mediated by
      ectopic release of transmitter from presynaptic elements directly facing the BG
      membrane.

PMID- 16107642
TI  - Vesicle-mediated transport and release of CCL21 in endangered neurons: a possible
      explanation for microglia activation remote from a primary lesion.
AB  - Whenever neurons in the CNS are injured, microglia become activated. In addition
      to local activation, microglia remote from the primary lesion site are
      stimulated. Because this so-called secondary activation of microglia is
      instrumental for long-term changes after neuronal injury, it is important to
      understand how microglia activity is controlled. The remote activation of
      microglia implies that the activating signals are transported along neuronal
      projections. However, the identity of these signals has not yet been identified.
      It is shown here that glutamate-treated neurons rapidly express and release the
      chemokine CCL21. We also provide evidence that neuronal CCL21 is packed in
      vesicles and transported throughout neuronal processes to reach presynaptic
      structures. Chemotaxis assays show that functional CCL21 is released from
      endangered neurons and activate microglia via the chemokine receptor CXCR3. Based
      on these findings, we suggest that neuronal CCL21 is important in directed neuron
      microglia signaling and that this communication could account for the remote
      activation of microglia, far distant from a primary lesion.

PMID- 16107643
TI  - Complex regulation of spiral ganglion neuron firing patterns by neurotrophin-3.
AB  - Auditory information is conveyed into the CNS via the spiral ganglion neurons,
      cells that possess distinctive electrophysiological properties that vary
      according to their cochlear innervation. Neurons from the base of the cochlea
      fire action potentials with shorter latencies and durations with more rapid
      accommodation than apical neurons (Adamson et al., 2002b). Interestingly, these
      features are altered by exposure to brain-derived neurotrophic factor and
      neurotrophin-3 (NT-3), suggesting that the electrophysiological diversity is not
      preprogrammed into the neurons but instead results from extrinsic regulation. In
      support of this, gradients of neurotrophins exist in the cochlea that could
      account for the apex- base differences in firing. To understand the determinants
      of spiral ganglion function, we characterized the NT-3 concentration dependence
      and mode of action on spiral ganglion neurons. Whole-cell current-clamp
      recordings were made from mouse basal spiral ganglion neurons (postnatal day 5)
      exposed to different concentrations of NT-3 for 3 d in vitro. Measurements of
      accommodation, latency, onset time course, and action potential latency revealed
      a nonmonotonic dependence on NT-3 concentration, with a peak effect occurring at
      10 ng/ml. Addition of NT-3 at different time points showed that neurotrophin
      exposure altered the firing features of existing neurons rather than supporting
      differential survival. These experiments establish that the electrophysiological
      phenotype of spiral ganglion neurons depends critically on the precise
      concentration of NT-3 and that the functional organization of this component of
      the peripheral auditory system results from a complex interplay between multiple
      kinds of neurotrophins and their cognate receptors.

PMID- 16107644
TI  - Loss of ALS2 function is insufficient to trigger motor neuron degeneration in
      knock-out mice but predisposes neurons to oxidative stress.
AB  - Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, is
      caused by a selective loss of motor neurons in the CNS. Mutations in the ALS2
      gene have been linked to one form of autosomal recessive juvenile onset ALS
      (ALS2). To investigate the pathogenic mechanisms of ALS2, we generated ALS2 knock
      out (ALS2(-/-)) mice. Although ALS2(-/-) mice lacked obvious developmental
      abnormalities, they exhibited age-dependent deficits in motor coordination and
      motor learning. Moreover, ALS2(-/-) mice showed a higher anxiety response in the
      open-field and elevated plus-maze tasks. Although they failed to recapitulate
      clinical or neuropathological phenotypes consistent with motor neuron disease by
      20 months of age, ALS2(-/-) mice or primary cultured neurons derived from these
      mice were more susceptible to oxidative stress compared with wild-type controls.
      These observations suggest that loss of ALS2 function is insufficient to cause
      major motor deficits or motor neuron degeneration in a mouse model but
      predisposes neurons to oxidative stress.

PMID- 16107645
TI  - Limited segregation of different types of sound localization information among
      classes of units in the inferior colliculus.
AB  - The auditory system uses three cues to decode sound location: interaural time
      differences (ITDs), interaural level differences (ILDs), and spectral notches
      (SNs). Initial processing of these cues is done in separate brainstem nuclei,
      with ITDs in the medial superior olive, ILDs in the lateral superior olive, and
      SNs in the dorsal cochlear nucleus. This work addresses the nature of the
      convergence of localization information in the central nucleus of the inferior
      colliculus (ICC). Ramachandran et al. (1999) argued that ICC neurons of types V,
      I, and O, respectively, receive their predominant inputs from ITD-, ILD-, and SN
      sensitive brainstem nuclei, suggesting that these ICC response types should be
      differentially sensitive to localization cues. Here, single-unit responses to
      simultaneous manipulation of pairs of localization cues were recorded, and the
      mutual information between discharge rate and individual cues was quantified.
      Although rate responses to cue variation were generally consistent with those
      expected from the hypothesized anatomical connections, the differences in
      information were not as large as expected. Type I units provide the most
      information, especially about SNs in the physiologically useful range. Type I and
      O units provide information about ILDs, even at low frequencies at which actual
      ILDs are very small. ITD information is provided by a subset of all low-frequency
      neurons. Type V neurons provide information mainly about ITDs and the average
      binaural intensity. These results are the first to quantify the relative
      representation of cues in terms of information and suggest a variety of degrees
      of cue integration in the ICC.

PMID- 16107646
TI  - Telencephalic embryonic subtractive sequences: a unique collection of
      neurodevelopmental genes.
AB  - The vertebrate telencephalon is composed of many architectonically and
      functionally distinct areas and structures, with billions of neurons that are
      precisely connected. This complexity is fine-tuned during development by numerous
      genes. To identify genes involved in the regulation of telencephalic development,
      a specific subset of differentially expressed genes was characterized. Here, we
      describe a set of cDNAs encoded by genes preferentially expressed during
      development of the mouse telencephalon that was identified through a functional
      genomics approach. Of 832 distinct transcripts found, 223 (27%) are known genes.
      Of the remaining, 228 (27%) correspond to expressed sequence tags of unknown
      function, 58 (7%) are homologs or orthologs of known genes, and 323 (39%)
      correspond to novel rare transcripts, including 48 (14%) new putative noncoding
      RNAs. As an example of this latter group of novel precursor transcripts of micro
      RNAs, telencephalic embryonic subtractive sequence (TESS) 24.E3 was functionally
      characterized, and one of its targets was identified: the zinc finger
      transcription factor ZFP9. The TESS transcriptome has been annotated, mapped for
      chromosome loci, and arrayed for its gene expression profiles during neural
      development and differentiation (in Neuro2a and neural stem cells). Within this
      collection, 188 genes were also characterized on embryonic and postnatal tissue
      by in situ hybridization, demonstrating that most are specifically expressed in
      the embryonic CNS. The full information has been organized into a searchable
      database linked to other genomic resources, allowing easy access to those who are
      interested in the dissection of the molecular basis of telencephalic development.

PMID- 16107647
TI  - Differential vesicular targeting and time course of synaptic secretion of the
      mammalian neurotrophins.
AB  - Neurotrophins are a family of secreted neuronal survival and plasticity factors
      comprising NGF, BDNF, neurotrophin-3 (NT-3), and NT-4. Whereas synaptic secretion
      of BDNF has been described, the routes of intracellular targeting and secretion
      of NGF, NT-3, and NT-4 in neurons are poorly understood. To allow for a direct
      comparison of intracellular targeting and release properties, all four mammalian
      neurotrophins were expressed as green fluorescent protein fusion proteins in
      cultured rat hippocampal neurons. We show that BDNF and NT-3 are targeted more
      efficiently to dendritic secretory granules of the regulated pathway of secretion
      (BDNF, in 98% of cells; NT-3, 85%) than NGF (46%) and NT-4 (23%). For all NTs,
      the remaining cells showed targeting to the constitutive secretory pathway.
      Fusing the BDNF pre-pro sequence to NT-4 directed NT-4 more efficiently to the
      regulated pathway of secretion. All neurotrophins, once directed to the regulated
      secretion pathway, were detected near synapsin I-positive presynaptic terminals
      and colocalized with PSD-95-DsRed (postsynaptic density-95-Discosoma red),
      suggesting postsynaptic targeting of the neurotrophins to glutamatergic synapses.
      Depolarization-induced release of all neurotrophins from synaptic secretory
      granules was slow (delay in onset, 10-30 s; tau = 120-307 s) compared with
      transmitter release kinetics monitored with FM4-64 [N-(3-triethylammoniumpropyl)
      4-(6-(4-diethylamino)phenyl)hexatrienyl)pyridinium dibromide] destaining (onset,
      <5 s; tau = 13 +/- 2 s). Among the neurotrophins, NT-4 secretion was most rapid
      but still proceeded 10 times more slowly than transmitter secretion.
      Preincubation of neurons with monensin (neutralizing intragranular pH, thus
      solubilizing the peptide core) increased the speed of secretion of BDNF, NGF, and
      NT-3 to the value of NT-4. These data suggest that peptide core dissolution in
      secretory granules is the critical determinant of the speed of synaptic secretion
      of all mammalian NTs and that the speed of release is not compatible with fast
      transmitter-like actions of neurotrophins.

PMID- 16107648
TI  - Regular exercise prolongs survival in a type 2 spinal muscular atrophy model
      mouse.
AB  - Several studies indicate that physical exercise is likely to be neuroprotective,
      even in the case of neuromuscular disease. In the present work, we evaluated the
      efficiency of running-based training on type 2 spinal muscular atrophy (SMA)-like
      mice. The model used in this study is an SMN (survival motor neuron)-null mouse
      carrying one copy of a transgene of human SMN2. The running-induced benefits
      sustained the motor function and the life span of the type 2 SMA-like mice by
      57.3%. We showed that the extent of neuronal death is reduced in the lumbar
      anterior horn of the spinal cord of running-trained mice in comparison with
      untrained animals. Notably, exercise enhanced motoneuron survival. We showed that
      the running-mediated neuroprotection is related to a change of the alternative
      splicing pattern of exon 7 in the SMN2 gene, leading to increased amounts of exon
      7-containing transcripts in the spinal cord of trained mice. In addition,
      analysis at the level of two muscles from the calf, the slow-twitch soleus and
      the fast-twitch plantaris, showed an overall conserved muscle phenotype in
      running-trained animals. These data provide the first evidence for the beneficial
      effect of exercise in SMA and might lead to important therapeutic developments
      for human SMA patients.

PMID- 16107649
TI  - Differential dynamic plasticity of A1 receptive fields during multiple spectral
      tasks.
AB  - Auditory experience leads to myriad changes in processing in the central auditory
      system. We recently described task-related plasticity characterized by rapid
      modulation of spectro-temporal receptive fields (STRFs) in ferret primary
      auditory cortex (A1) during tone detection. We conjectured that each acoustic
      task may have its own "signature" STRF changes, dependent on the salient cues
      that the animal must attend to perform the task. To discover whether other
      acoustic tasks could elicit changes in STRF shape, we recorded from A1 in ferrets
      also trained on a frequency discrimination task. Overall, we found a distinct
      pattern of STRF change, characterized by an expected selective enhancement at
      target tone frequency but also by an equally selective depression at reference
      tone frequency. When single-tone detection and frequency discrimination tasks
      were performed sequentially, neurons responded differentially to identical tones,
      reflecting distinct predictive values of stimuli in the two behavioral contexts.
      All results were observed in multiunit as well as single-unit recordings. Our
      findings provide additional evidence for the presence of adaptive neuronal
      responses in A1 that can swiftly change to reflect both sensory content and the
      changing behavioral meaning of incoming acoustic stimuli.

PMID- 16107650
TI  - Retinoic acid signaling identifies a distinct precursor population in the
      developing and adult forebrain.
AB  - We asked whether retinoic acid (RA), an established transcriptional regulator in
      regenerating and developing tissues, acts directly on distinct cell classes in
      the mature or embryonic forebrain. We identified a subset of slowly dividing
      precursors in the adult subventricular zone (SVZ) that is transcriptionally
      activated by RA. Most of these cells express glial fibrillary acidic protein, a
      smaller subset expresses the epidermal growth factor receptor, a few are terminal
      deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling
      positive, and they can be mitotically labeled by sustained rather than acute
      bromodeoxyuridine exposure. RA activation in similar cells in SVZ-derived
      neurospheres depends on retinoid synthesis from the premetabolite retinol. The
      apparent influence of RA on precursors in vitro is consistent with key properties
      of RA activation in the SVZ; in neurospheres, altered retinoid signaling elicits
      neither cell death nor an acute increase in cell proliferation. There is apparent
      continuity of RA signaling in the forebrain throughout life. RA-activated,
      proliferative precursors with radial glial characteristics are found in the
      dorsal lateral ganglionic eminence and ventrolateral palliumembryonic rudiments
      of the SVZ. Thus, endogenous RA signaling distinguishes subsets of neural
      precursors with glial characteristics in a consistent region of the adult and
      developing forebrain.

PMID- 16107651
TI  - Optical imaging of SI topography in anesthetized and awake squirrel monkeys.
AB  - Orderly topographic maps in the primary somatosensory cortex (SI) serve as an
      anchor for our understanding of somatosensory cortical organization. However,
      this view is mostly based on data collected in the anesthetized animal. Less is
      known about these topographies in the awake primate. Even less is known about the
      relative activations of different subdivisions of SI (areas 3a, 3b, 1, and 2).
      Toward the goal of understanding the functional activation of SI, we conducted
      intrinsic signal optical imaging of areas 3b and 1 in awake squirrel monkeys.
      Monkeys were imaged repeatedly for a period of >2 years in awake and anesthetized
      states in response to vibrotactile and electrocutaneous stimuli presented to
      individual fingerpads. During this period, we found stable somatotopic maps in
      both the anesthetized and awake states, consistent with electrophysiologically
      recorded maps in areas 3b and 1 in the anesthetized state. In the awake animal,
      signal sizes were larger, but variability was greater, leading to decreased
      signal-to-noise ratios. Topographic activations were larger (in both area and
      amplitude) in the awake animal, suggesting either a less precise topography
      and/or more complex integration. This brings into question the role of a precise
      topographic map during behavior. In addition, whereas in the anesthetized animal
      strongest imaging signals were obtained from area 3b, in the awake animal, area 1
      activation dominated over that in area 3b. Differences in relative dominance of
      area 3b versus area 1 suggest that inter-areal interactions in the alert animal
      differ substantially from that in the anesthetized animal.

PMID- 16107652
TI  - Large-conductance calcium-activated potassium channels facilitate transmitter
      release in salamander rod synapse.
AB  - Large-conductance calcium-activated potassium (BK) channels are colocalized with
      calcium channels at sites of exocytosis at the presynaptic terminals throughout
      the nervous system. It is expected that their activation would provide negative
      feedback to transmitter release, but the opposite is sometimes observed. Attempts
      to resolve this apparent paradox based on alterations in action potential
      waveform have been ambiguous. In an alternative approach, we investigated the
      influence of this channel on neurotransmitter release in a nonspiking neuron, the
      salamander rod photoreceptors. Surprisingly, the BK channel facilitates calcium
      mediated transmitter release from rods. The two presynaptic channels form a
      positive coupled loop. Calcium influx activates the BK channel current, leading
      to potassium efflux that increases the calcium current. The normal physiological
      voltage range of the rod is well matched to the dynamics of this positive loop.
      When the rod is further depolarized, then the hyperpolarizing BK channel current
      exceeds its facilitatory effect, causing truncation of transmitter release. Thus,
      the calcium channel-BK channel linkage performs two functions at the synapse:
      nonlinear potentiator and safety brake.

PMID- 16107653
TI  - Src-dependent tyrosine phosphorylation at the tips of growth cone filopodia
      promotes extension.
AB  - Extracellular cues guide axon outgrowth by activating intracellular signaling
      cascades that control the growth cone cytoskeleton. However, the spatial and
      temporal coordination of signaling intermediates remains essentially unknown.
      Live imaging of tyrosine phosphorylation in growth cones revealed dynamic phospho
      tyrosine (PY) signals in filopodia that directly correlate with filopodial
      behavior. Local PY signals are generated at distal tips of filopodia during
      extension and are lost during retraction. Active Src family kinases localize to
      the tips of filopodia, and Src activity regulates both filopodial dynamics and
      local PY signaling. Positive guidance cues stimulate filopodial motility by
      locally increasing tyrosine phosphorylation in a cell division cycle 42 (Cdc42)
      dependent manner. Locally reduced Src activity on one side of the growth cone
      generates an asymmetry in filopodial motility and PY signaling that promotes
      repulsive turning, suggesting that local changes in filopodial PY levels may
      underlie growth cone pathfinding decisions. p21-activated kinase (PAK), a Cdc42
      effector whose activity is regulated by Src phosphorylation, also localizes to
      the tips of extending filopodia and controls filopodial motility. Coordinated
      activation of cytoskeletal effector proteins by GTPase binding and Src-mediated
      tyrosine phosphorylation may function to produce specific growth cone behaviors
      in response to guidance cues.

PMID- 16107654
TI  - A calcium flux is required for circadian rhythm generation in mammalian pacemaker
      neurons.
AB  - Generation of mammalian circadian rhythms involves molecular transcriptional and
      translational feedback loops. It is not clear how membrane events interact with
      the intracellular molecular clock or whether membrane activities are involved in
      the actual generation of the circadian rhythm. We examined the role of membrane
      potential and calcium (Ca2+) influx in the expression of the circadian rhythm of
      the clock gene Period 1 (Per1) within the rat suprachiasmatic nucleus (SCN), the
      master pacemaker controlling circadian rhythmicity. Membrane hyperpolarization,
      caused by lowering the extracellular concentration of potassium or blocking Ca2+
      influx in SCN cultures by lowering [Ca2+], reversibly abolished the rhythmic
      expression of Per1. In addition, the amplitude of Per1 expression was markedly
      decreased by voltage-gated Ca2+ channel antagonists. A similar result was
      observed for mouse Per1 and PER2. Together, these results strongly suggest that a
      transmembrane Ca2+ flux is necessary for sustained molecular rhythmicity in the
      SCN. We propose that periodic Ca2+ influx, resulting from circadian variations in
      membrane potential, is a critical process for circadian pacemaker function.

PMID- 16107655
TI  - Neuroleptic-induced catalepsy: electrophysiological mechanisms of functional
      recovery induced by high-frequency stimulation of the subthalamic nucleus.
AB  - High-frequency stimulation (HFS) of the subthalamic nucleus (STN) remarkably
      alleviates motor disorders in parkinsonian patients. The mechanisms by which STN
      HFS exerts its beneficial effects were investigated in anesthetized rats, using a
      model of acute interruption of dopaminergic transmission. Combined systemic
      injections of SCH-23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5,
      tetrahydro-1H-3-benzazepine] and raclopride, antagonists of the D1 and D2 classes
      of dopaminergic receptors, respectively, were performed, and the parameters of
      STN HFS that reversed the neuroleptic-induced catalepsy were determined in freely
      moving animals. The effects of neuroleptics and the impact of STN HFS applied at
      parameters alleviating neuroleptic-induced catalepsy were analyzed in the
      substantia nigra pars reticulata (SNR), a major basal ganglia output structure,
      by recording the neuronal firing pattern and the responses evoked by cortical
      stimulation. Neuroleptic injection altered the tonic and regular mode of
      discharge of SNR neurons, most of them becoming irregular with bursts of spikes
      and pauses. The inhibitory component of the cortically evoked response, which is
      attributable to the activation of the direct striatonigral circuit, was
      decreased, whereas the late excitatory response resulting from the indirect
      striato-pallido-subthalamo-nigral circuit was reinforced. During STN HFS, the
      spontaneous firing of SNR cells was either increased or decreased with a global
      enhancement of the firing rate in the overall population of SNR cells recorded.
      However, in all of the cases, SNR firing pattern was regularized, and the bias
      between the trans-striatal and trans-subthalamic circuits was reversed. By these
      effects, STN HFS restores the functional properties of the circuits by which
      basal ganglia contribute to motor activity.

PMID- 16107656
TI  - Hippocampal synaptic metaplasticity requires inhibitory autophosphorylation of
      Ca2+/calmodulin-dependent kinase II.
AB  - Virtually all CNS synapses display the potential for activity-dependent long-term
      potentiation (LTP) and/or long-term depression (LTD). Intriguingly, the potential
      to exhibit LTP or LTD at many central synapses itself is powerfully modulated by
      previous synaptic activity. This higher-order form of plasticity has been termed
      metaplasticity. Here, we show that inhibitory autophosphorylation of
      Ca2+/calmodulin-dependent kinase II (CaMKII) is required for hippocampal
      metaplasticity at the lateral perforant path-dentate granule cell synapse. Brief
      10 Hz priming, which does not affect basal synaptic transmission, caused a
      dramatic, pathway-specific and long-lasting (up to 18 h) reduction in
      subsequently evoked LTP at lateral perforant path synapses. In contrast, LTD was
      unaffected by priming. The induction of lateral perforant path metaplasticity
      required the activation of NMDA receptors during priming. In addition,
      metaplasticity was absent in knock-in mice expressing alphaCaMKII that cannot
      undergo inhibitory phosphorylation, indicating that inhibitory
      autophosphorylation of alphaCaMKII at threonines 305/306 is required for
      metaplasticity. Metaplasticity was not observed in the medial perforant pathway,
      consistent with the observation that CaMKII activity was not required for the
      induction of LTP at this synapse. Thus, modulation of alphaCaMKII activity via
      autophosphorylation at Thr305/Thr306 is a key mechanism for metaplasticity that
      may be of importance in the integration of temporally separated episodes of
      activity.

PMID- 16107658
TI  - Beta testing.

PMID- 16107659
TI  - Hairy breakup.

PMID- 16107660
TI  - Making young tumors old: a new weapon against cancer?
AB  - As the population of industrial nations ages, the incidence of cancer and cancer
      mortality is increasing. Intuitively, older organisms may be less able to cope
      with accumulated damage and thus be more prone to develop cancer. However, so
      far, the links between aging and cancer have been only partially explored.
      Strikingly, four recent studies now indicate that premature senescence
      accompanied by cell cycle arrest occurs in tumors initiated by an oncogenic
      mutation. Thus, senescence may act as a key tumor suppressor mechanism in young
      tumors in vivo.

PMID- 16107661
TI  - Epidemiology of chronic wasting disease in free-ranging mule deer: spatial,
      temporal, and demographic influences on observed prevalence patterns.
AB  - We analyzed chronic wasting disease (CWD) prevalence data from mule deer
      populations in northcentral Colorado, USA, to discern the likely influences of
      temporal, spatial, and demographic factors on patterns observed in naturally
      infected populations. In addition to reaffirming spatial heterogeneity among
      wintering mule deer subpopulations, we report marked differences in CWD
      prevalence by sex and age groups as well as clear local trends of increasing
      prevalence over a 7-yr period. Prevalence of CWD differed by age (yearling vs.
      adult), sex, and geographic area at two different spatial scales (game management
      unit or population unit winter range) and increased over time at both geographic
      scales. Disease status (positive or negative) was not independent of age for
      males (n=285, df=6, chi2=18.4, P=0.005) or females (n=387, df=8, chi2=17.2,
      P=0.028). Among males, prevalence increased and then declined across age classes,
      peaking in 5- to 6-yr-old individuals; among females, prevalence showed no
      definite age-related pattern. Demographic, spatial, and temporal factors all
      appear to contribute to the marked heterogeneity in CWD prevalence in endemic
      portions of northcentral Colorado, USA. These factors likely combine in various
      ways to influence epidemic dynamics on both local and broad geographic scales.

PMID- 16107662
TI  - Associations between water quality, Pasteurella multocida, and avian cholera at
      Sacramento National Wildlife Refuge.
AB  - We studied patterns in avian cholera mortality, the presence of Pasteurella
      multocida in the water or sediment, and water chemistry characteristics in 10
      wetlands at the Sacramento National Wildlife Refuge Complex (California, USA), an
      area of recurrent avian cholera epizootics, during the winters of 1997 and 1998.
      Avian cholera outbreaks (>or=50 dead birds) occurred on two wetlands during the
      winter of 1997, but no P. multocida were recovered from 390 water and 390
      sediment samples from any of the 10 wetlands. No mortality events were observed
      on study wetlands during the winter of 1998; however, P. multocida was recovered
      from water and sediment samples in six of the 10 study wetlands. The pH levels
      were higher for wetlands experiencing outbreaks during the winter of 1997 than
      for nonoutbreak wetlands, and aluminum concentrations were higher in wetlands
      from which P. multocida were recovered during the winter of 1998. Water chemistry
      parameters (calcium, magnesium, sodium, and dissolved protein) previously linked
      with P. multocida and avian cholera mortality were not associated with the
      occurrence of avian cholera outbreaks or the presence of P. multocida in our
      study wetlands. Overall, we found no evidence to support the hypothesis that
      wetland characteristics facilitate the presence of P. multocida and, thereby,
      allow some wetlands to serve as long-term sources (reservoirs) for P. multocida.

PMID- 16107663
TI  - Diseases and mortality in free-ranging brown bear (Ursus arctos), gray wolf
      (Canis lupus), and wolverine (Gulo gulo) in Sweden.
AB  - Ninety-eight brown bears (Ursus arctos), 20 gray wolves (Canis lupus), and 27
      wolverines (Gulo gulo), all free-ranging, were submitted to the National
      Veterinary Institute, Uppsala, Sweden, during 1987-2001 for investigation of
      diseases and causes of mortality. The most common cause of natural death in brown
      bears was infanticide. Infanticide also was observed in wolverines but not in
      wolves. Traumatic injuries, originating from road or railway accidents, were the
      most common cause of death in wolves and occurred occasionally in brown bears.
      Most wolverines were submitted as forensic cases in which illegal
      hunting/poaching was suspected. Sarcoptic mange was observed in several wolves
      but not in brown bears or wolverines. Sarcoptic mange most likely was acquired
      from infected red foxes (Vulpes vulpes) that were killed by wolves. Other
      parasites and infectious diseases were only found sporadically.

PMID- 16107664
TI  - Prevalence of Trichomonas gallinae in northern goshawks from the Berlin area of
      northeastern Germany.
AB  - In recent years, the northern goshawk (Accipiter gentilis) has colonized suburban
      and urban areas in Berlin, Germany, and elsewhere in Europe. Because of the high
      proportion of feral pigeons (Columba livia f. domestica) in their diet, urban
      goshawks are suspected to have a high infection rate with Trichomonas gallinae.
      Therefore, from 1998 to 2001, we examined 269 nestlings from 90 nests for
      infection with T. gallinae by culture of swabs taken from the oropharynx and
      checked their oropharynx for the presence of caseous lesions indicative of
      trichomonosis. In 80% of the nest sites (n=90), at least one nestling was
      infected. The nestling infection rate with T. gallinae was 69.7% (n=33) in 1998,
      73.0% (n=89) in 1999, 55.8% (n=77) in 2000, and 62.9% (n=70) in 2001. In total,
      65.1% of the northern goshawk nestlings were culture positive for T. gallinae.
      Prevalence increased with the age of nestlings (chi2=12.4, n=269, df=5, P=0.03)
      and tended to increase with brood size (chi2=9.345, n=269, df=4, P=0.053).
      Caseous lesions were present in 12 nestlings (4.5%), but only 10 of these were
      culture positive for T. gallinae. Two nestlings (0.7%) had large caseous lesions
      (diameter>1 cm) characteristic of late-stage trichomonosis and died shortly after
      examination. It is suggested that the combination of a high prevalence of T.
      gallinae with a low rate of pathologicic changes is the result of an evolutionary
      adapted parasite-host relationship.

PMID- 16107665
TI  - Serologic survey for selected virus infections in polar bears at Svalbard.
AB  - Polar bears (Ursus maritimus) were chemically immobilized and sampled at
      Svalbard, Norway, and on the pack ice in the Barents Sea from late March to mid
      May between 1990 and 1998. Plasma samples were tested for the presence of
      antibodies to canine distemper virus (CDV), calicivirus, phocid herpesvirus type
      1 (PhHV-1), and rabies virus. A seroprevalence of 8% to CDV and 2% to calicivirus
      were found, whereas no antibodies were detected against PhHV-1 or rabies virus.
      This serologic survey indicates that polar bears in this region are exposed to
      morbillivirus and calicivirus, although the nature of these viruses and
      infections are unknown. Morbillivirus and calicivirus are potential pathogens in
      seals, but it is unknown whether they may cause health problems in polar bears.

PMID- 16107666
TI  - Susceptibility of wild songbirds to the house finch strain of Mycoplasma
      gallisepticum.
AB  - Conjunctivitis in house finches (Carpodacus mexicanus), caused by Mycoplasma
      gallisepticum (MG), was first reported in 1994 and, since this time, has become
      endemic in house finch populations throughout eastern North America. Although the
      house finch is most commonly associated with MG-related conjunctivitis, MG has
      been reported from other wild bird species, and conjunctivitis (not confirmed as
      MG related) has been reported in over 30 species. To help define the host range
      of the house finch strain of MG and to better understand the effect of MG on
      other host species, we monitored a community of wild birds for exposure to MG and
      conducted experimental infections on nine avian species. For the field portion of
      our study, we conducted a 9-mo survey (August 2001 to April 2002) of wild avian
      species in a peri-urban environment on the campus of Auburn University. During
      this time 358 birds, representing 13 different families, were sampled. No
      clinical signs of mycoplasmosis were observed in any bird. Thirteen species from
      nine families had positive agglutination reactions for antibodies to MG, but all
      birds tested negative by polymerase chain reaction (PCR). Three mourning doves
      were PCR-positive for MG, but antibodies to MG were not detected. In the
      experimental infections, we exposed seven native avian species and two cage-bird
      species to MG (May 2000 to June 2002). After exposure, clinical disease was seen
      in all four species from the family Fringillidae and in eastern tufted titmice
      (Baeolophus bicolor). In addition, three other species were infected without
      clinical signs, suggesting that they may represent potential MG reservoirs.

PMID- 16107667
TI  - Re-exposure of captive house finches that recovered from Mycoplasma gallisepticum
      infection.
AB  - Fourteen house finches were reinoculated (re-exposed) with 0.05 ml (3.24x10(5)
      colony forming units/ml) of Mycoplasma gallisepticum (MG) in the conjunctival sac
      of each eye. All birds used in this reinoculation study had recovered from
      previous infection between 27 and 83 days after inoculation. Recovery was based
      on the absence of clinical signs of conjunctivitis and/ or the inability to
      detect MG in conjunctival or choanal samples. Birds were maintained in individual
      cages under controlled environmental conditions at temperature 21-24 C, relative
      humidity 70%, and a light cycle adjusted to ambient values. They were divided
      into three groups, (A, B, and C). Five birds each were reinoculated 219 days (7.3
      mo, group A) and 314 days (10.47 mo, group B) after the original infection. The
      final group of four birds was reinoculated at 425 days after experimental
      infection (14.17 mo, group C). Although the birds were randomly assigned to the
      three groups, the duration of the disease state (number of days until clinical
      signs last observed) during initial infection differed: group A mean=37.0+/-SE
      4.549, group B mean=63.6+/-SE 6.306, group C mean=42.75+/-SE 2.750; analysis of
      variance F2,11=8.17, P=0.007. Within 24 hr after reinoculation six of the 14
      experimental birds had developed some clinical signs of MG-induced
      conjunctivitis. At 3 days after reinoculation, 12 of the 14 birds had unilateral
      or bilateral conjunctivitis. The duration of clinical signs in the reinoculated
      individuals was significantly shorter than with their previous infection. These
      results suggest that the birds were able to mount a rapid and strong immune
      response following re-exposure. However, they were susceptible to reinfection and
      developed disease, suggesting that reinfection or perhaps even recurrence of
      infection and disease could occur in the free-ranging population. This may
      represent an important component in the epidemiology of this disease in house
      finches.

PMID- 16107668
TI  - Enumeration and antibiotic resistance patterns of fecal indicator organisms
      isolated from migratory Canada geese (Branta canadensis).
AB  - Thermotolerant fecal indicator organisms carried by migratory waterfowl may serve
      as reservoirs of antibiotic resistance. To determine the extent to which such
      antibiotic resistance markers were present in migratory Canada geese (Branta
      canadensis) on the Maryland Eastern Shore, we isolated Enterococcus spp. and
      Escherichia coli from fresh feces and examined the antibiotic resistance profiles
      of these bacteria. Samples were obtained in October 2002, January 2003, and March
      2003. Thermotolerant E. coli counts ranged from 0 to 1.0x10(7) colony forming
      units (CFU)/0.1g (g-1) wet weight of feces, whereas Enterococcus spp. counts
      ranged from 1.0x10(2)-1.0x10(7) CFU g-1 wet weight of feces. Primary isolates of
      each indicator organism were tested against a panel of 10 antibiotics. Greater
      than 95% of E. coli isolates were resistant to penicillin G, ampicillin,
      cephalothin, and sulfathiazole; no E. coli were resistant to ciprofloxacin.
      Enterococcal isolates showed highest resistance to cephalothin, streptomycin, and
      sulfathiazole; no enterococci were resistant to chloramphenicol. The
      tetracyclines, streptomycin, and gentamycin provided the greatest discrimination
      among E. coli isolates; chlortetracycline, cephalothin, and gentamycin resistance
      patterns provided the greatest discrimination between enterococcal strains.
      Multiple antibiotic resistance (MAR) profiles were calculated: fall (E.
      coli=0.499; enterococci=0.234), winter (E. coli=0.487; enterococci=0.389), and
      spring (E. coli=0.489; enterococci=0.348). E. faecalis and E. faecium, which are
      recognized human nosocomial pathogens, were cultured from winter (44 and 56%,
      respectively) and spring (13 and 31%, respectively) fecal samples.

PMID- 16107669
TI  - Characterization of canarypox-like viruses infecting endemic birds in the
      Galapagos Islands.
AB  - The presence of avian pox in endemic birds in the Galapagos Islands has led to
      concern that the health of these birds may be threatened by avipoxvirus
      introduction by domestic birds. We describe here a simple polymerase chain
      reaction-based method for identification and discrimination of avipoxvirus
      strains similar to the fowlpox or canarypox viruses. This method, in conjunction
      with DNA sequencing of two polymerase chain reaction-amplified loci totaling
      about 800 bp, was used to identify two avipoxvirus strains, Gal1 and Gal2, in pox
      lesions from yellow warblers (Dendroica petechia), finches (Geospiza spp.), and
      Galapagos mockingbirds (Nesomimus parvulus) from the inhabited islands of Santa
      Cruz and Isabela. Both strains were found in all three passerine taxa, and
      sequences from both strains were less than 5% different from each other and from
      canarypox virus. In contrast, chickens in Galapagos were infected with a virus
      that appears to be identical in sequence to the characterized fowlpox virus and
      about 30% different from the canarypox/Galapagos group viruses in the regions
      sequenced. These results indicate the presence of canarypox-like viruses in
      endemic passerine birds that are distinct from the fowlpox virus infecting
      chickens on Galapagos. Alignment of the sequence of a 5.9-kb region of the genome
      revealed that sequence identities among Gal1, Gal2, and canarypox viruses were
      clustered in discrete regions. This indicates that recombination between poxvirus
      strains in combination with mutation led to the canarypox-like viruses that are
      now prevalent in the Galapagos.

PMID- 16107670
TI  - West Nile virus detection in the organs of naturally infected blue jays
      (Cyanocitta cristata).
AB  - Blue jays (Cyanocitta cristata) are an effective indicator species for West Nile
      virus (WNV) and may be regionally important in surveillance efforts. The sites of
      WNV replication and sensitivity of virus detection techniques are undefined for
      blue jays. The objectives of this study were to describe the gross and
      microscopic pathology associated with natural WNV infection in blue jays, as well
      as determine the most appropriate tissues to be used for virus isolation, reverse
      transcription-nested polymerase chain reaction, and immunohistochemistry (IHC)
      techniques. Blue jays were collected in Georgia, USA, between May and September
      2001. Initial screening by virus isolation indicated that 36 of 59 blue jays
      chosen for evaluation were WNV positive. From this group, 20 positive and five
      negative birds were chosen to compare virus detection techniques. Six positive
      and five negative birds were selected for histopathology examination.
      Splenomegaly and poor body condition were the most consistent gross findings
      among positive birds. The most consistent histopathologic findings in the tissues
      of WNV-positive blue jays were mononuclear leukocytosis and
      epicarditis/myocarditis. Brain, heart, and lung had the highest viral titers, and
      WNV antigen was most often detected by IHC in heart, kidney, liver, and lung.
      Reverse transcription-nested polymerase chain reaction proved to be the most
      sensitive diagnostic test applied in this study irrespective of the tissue type.
      Brain tissue could be used effectively for both virus isolation and RT-nPCR, and
      this tissue is simple to remove and process. The success of IHC is highly
      dependent on tissue selection, and the use of multiple tissues including heart,
      kidney, liver, or lung is recommended.

PMID- 16107671
TI  - Toxicity of sodium chloride to house sparrows (Passer domesticus).
AB  - Sodium chloride (NaCl) is widely used as a deicing agent on roadways. There are
      numerous anecdotal reports of poisoning of passerine birds by road salt in the
      United States and Canada, but little is known about the toxicity of NaCl to
      songbirds. The objectives of this study were to determine the lethal dose range
      for NaCl in a representative passerine species (house sparrow [Passer
      domesticus]); to determine the clinical, physiologic, and pathologic effects of
      sublethal and lethal oral NaCl exposure; and to assess the potential for recovery
      after exposure to granular salt or highly concentrated salt solutions. The up-and
      down method was used in a pilot study to estimate the lethal oral dose of
      granular NaCl in wild caught house sparrows. The toxicity of highly concentrated
      NaCl solution also was investigated. This was followed by an acute dose response
      study in which house sparrows were dosed orally with granular NaCl at 0, 500,
      1,500, 2,500, or 3,500 mg/kg. Sparrows were deprived of water for 6 hr
      postexposure (PE) in an attempt to mimic specific winter conditions. Groups of
      three birds at each dose were euthanized at 1, 3, 6, and 12 hr PE, and samples
      were collected for histopathology and brain and plasma electrolyte analyses.
      Results indicated an approximate mean lethal dose (LD50) of 3,000-3,500 mg/kg in
      water-deprived birds, which is similar to mammalian values. House sparrows dosed
      with a concentrated solution of NaCl generally died at doses of 8,000 mg/kg.
      Clinical signs observed at >or=1,500 mg/kg included rapid onset (<30 min) of
      depression (indicated by reduced activity and reduced response to visual and
      auditory stimuli), ataxia, inability to fly or perch, and death in as little as
      45 min. Birds that survived for 6 hr usually recovered. Plasma Na concentrations
      >200 mmol/l were consistently associated with clinical signs. Pathologic lesions
      consisted of edema and distension of the caudoventral thin muscled region of the
      gizzard and were observed 1 hr PE in most birds dosed with >or=500 mg/kg. Brain
      Na concentrations in clinically ill sparrows and those that died of NaCl toxicity
      ranged from 1,297 to 1,615 (mean=1,450; SD=115) ppm wet weight or 5,603 to 6,958
      (mean=6,367; SD=454) ppm dry weight, which differed significantly from control
      birds. No histologic lesions were observed in brain sections of exposed birds,
      likely reflecting the acute nature of the exposure. However, fluid accumulation
      beneath the koilin layer of the gizzard was observed in the majority of birds at
      high dosage levels. These results indicate that passerines ingesting relatively
      small numbers of road salt granules or small quantities of highly concentrated
      NaCl solutions are at risk of sodium poisoning.

PMID- 16107672
TI  - Pathological features in marine birds affected by the prestige's oil spill in the
      north of Spain.
AB  - A total of 2,465 seabirds, mainly common murres (Uria aalge), razorbills (Alca
      torda), and puffins (Fratercula arctica) that beached in the northwestern part of
      Spain after the "Prestige" oil spill on 19 November 2002 were examined by
      pathological methods. Birds were divided into three groups: dead birds with the
      body covered (group 1) or uncovered (group 2) by oil and birds recovered alive
      but which died after being treated at a rescue center (group 3). The main gross
      lesions were severe dehydration and emaciation. Microscopically, hemosiderin
      deposits, related to cachexia and/or hemolytic anemia, were observed in those
      birds harboring oil in the intestine. Severe aspergillosis and ulcers in the
      ventriculus were found only in group 3 birds, probably because of stress
      associated with attempted rehabilitation at the rescue center. The mild character
      of the pathological changes suggests that petroleum oil toxicosis causes multiple
      sublethal changes that have an effect on the ability of the birds to survive at
      sea, especially weak and young, inexperienced animals. Dehydration and exhaustion
      seem to be the most likely cause of death.

PMID- 16107673
TI  - Hematologic, protein electrophoresis, biochemistry, and cholinesterase values of
      free-living black stork nestlings (Ciconia nigra).
AB  - Hematologic, protein electrophoresis, serum biochemistry, and cholinesterase
      values were determined in 36 free-living black stork nestlings (Ciconia nigra)
      between 25 and 53 days of age in order to establish normal reference values for
      this population. The following values were evaluated: white blood cell counts,
      red blood cell counts, packed cell volume, hemoglobin, heterophils, lymphocytes,
      monocytes, eosinophils, prealbumin, albumin, alpha-globulin, beta-globulin, gamma
      globulin, total protein, aspartate aminotransferase, alkaline phosphatase,
      lactate dehydrogenase, creatine kinase, calcium, phosphorus, iron, cholesterol,
      glucose, triglycerides, uric acid, urea, creatinine, total solids, bile acids,
      and butyrylcholinesterase. Sex-dependent differences were observed in hemoglobin,
      prealbumin, albumin, gamma-globulin, total protein, alkaline phosphatase, and
      triglycerides. Packed cell volume, butyrylcholinesterase, aspartate
      aminotransferase, creatine kinase, and creatinine increased with age, whereas
      albumin, mean cell volume, calcium, phosphorus, cholesterol, and total solids
      decreased with age. These hematologic and serum biochemistry values can be used
      as reference ranges in free-living black stork nestlings.

PMID- 16107674
TI  - Hematologic responses in captive white-winged doves (Zenaida asiatica), induced
      by various radiotransmitter attachments.
AB  - White blood cell counts, heterophil-lymphocyte ratios, and leukocyte
      differentials of captive white-winged doves (Zenaida asiatica) from Texas
      equipped with different radiotransmitter attachment packages were monitored.
      Doves were segregated by gender and age by males, females, and hatching year;
      individuals housed in 30 large outdoor pens in groups of seven. Treatments
      consisted of controls, glue-on transmitters, body loop harnesses, surgically
      implanted intracoelomic transmitters, surgically implanted subcutaneous
      transmitters, intracoelomic surgery without implants, and subcutaneous surgery
      without implants. We used multivariate analysis of variance with pen as a
      blocking variable and gender nested and repeated measures analysis of variance to
      identify differences among any of the transmitter attachment techniques and the
      control for dependent variables. We found no difference in blood parameters
      between transmitter attachment technique versus a control.

PMID- 16107675
TI  - Efficacy of immobilizing free-ranging elk with Telazol and xylazine hydrochloride
      using transmitter-equipped darts.
AB  - From January 1999 to April 2002, 14 free-ranging elk were darted with a mixture
      of Telazol reconstituted with xylazine hydrochloride (HCl) in a forested habitat
      in southwestern Oklahoma and north-central Arkansas. Elk were darted from ground
      blinds, tree stands, or a vehicle at distances of 14-46 m and were recovered 37
      274 m from the dart site. Elk were located using radiotelemetry with 3-cc
      disposable Pneu-dart transmitter darts. Mean+/-SD dose of Telazol and xylazine
      HCl was 590+/-192 mg/ml and 276+/-153 mg/ml, respectively, and mean time to
      standing after injection of reversal agent was 27 min (range: 1-65 min). The
      combination of Telazol and xylazine HCl successfully immobilized free-ranging
      elk, and transmitter-equipped darts permitted successful location of sedated elk
      by two people in areas of dense forest cover. The dose required to sedate elk
      appeared to vary depending on physiology and behavior, but no drug-induced
      mortality occurred despite the wide variance in the doses administered. We
      recommend 500 mg Telazol reconstituted with 300 mg xylazine HCl as an initial
      dose for a >or=200 kg elk. If needed to achieve full sedation, up to 3 additional
      ml of the mixture may be administered without adverse effects.

PMID- 16107676
TI  - Naturally occurring secondary nutritional hyperparathyroidism in cattle egrets
      (Bubulcus ibis) from central Texas.
AB  - Naturally occurring secondary nutritional hyperparathyroidism is described in the
      nestlings of two colonies of cattle egrets (Bubulcus ibis) from Central Texas
      (Bryan and San Antonio, Texas, USA). Nestlings from a third colony (Waco, Texas,
      USA) were collected in a subsequent year for comparison. Birds from the first two
      colonies consistently had severe osteopenia and associated curving deformities
      and folding fractures of their long bones. These birds also had reduced bone ash,
      increased osteoclasia, a marked decrease in osteoblast activity, variable
      lengthening and shortening of the hypertrophic zone of the epiphyseal cartilage,
      decreased and disorganized formation of new bone, and a marked hypertrophy and
      hyperplasia of the parathyroid glands as compared to birds collected from the
      third colony. Fibrous osteodystrophy was found in all of the birds from San
      Antonio and Bryan. Evidence of moderate to severe calcium deficiency was also
      identified in 33% of the cattle egrets collected from Waco. Gut contents of
      affected chicks contained predominately grasshoppers and crickets; vertebrate
      prey items were absent from the Bryan birds. Grasshoppers and crickets collected
      from fields frequented by the adult egrets in 1994 had 0.12-0.28% calcium and
      0.76-0.81% phosphorus. Pooled grasshoppers and crickets collected during a
      subsequent wet early spring averaged 0.24% calcium and 0.65% phosphorus. Although
      the phosphorus content of the insect prey was adequate for growth, calcium was
      approximately one-third the minimum calcium requirement needed for growth for
      other species of birds. It was postulated that cattle egrets breeding in Central
      Texas have expanded their range into habitat that contains less vertebrate prey,
      and as a result, many nestling egrets are being fed diets that contain suboptimal
      calcium. Therefore, in years where vertebrate prey is scarce and forage for
      insect prey is reduced in calcium, nestling egrets are at risk for developing
      secondary nutritional hyperparathyroidism.

PMID- 16107677
TI  - Relationships among fecal lungworm loads, fecal glucocorticoid metabolites, and
      lamb recruitment in free-ranging Rocky Mountain bighorn sheep.
AB  - Most wild Rocky Mountain big-horn sheep (Ovis canadensis canadensis) in northern
      latitudes are infected with lungworms. Indirect effects of lungworms on bighorn
      sheep are unknown, but high pulmonary burdens might increase stress (i.e.,
      elevated glucocorticoid levels), and chronic stress could in turn decrease
      fitness. We hypothesized that high lungworm burdens in Rocky Mountain bighorn
      ewes increase stress, thereby increasing lamb mortality. To test our hypothesis,
      one subherd of bighorn sheep in Custer State Park, South Dakota was provided a
      free-choice loose mineral mix containing the anthelmintic fenbendazole every six
      weeks from March 1999 to August 2000 to eliminate lungworms; another subherd
      served as the control. Daily, individually marked ewes were located
      telemetrically from the ground and uniquely marked animals were observed until
      they defecated. After the herd moved from the area, fecal samples were collected
      and stored at -23 C. A consistent number of samples per season per herd (x
      =16.56+/-3.99 samples) were collected. Fecal larval lungworm levels (LPG) in the
      treatment subherd were lower than levels in the control subherd; however, there
      was no difference in fecal glucocorticoid metabolite (FGM) levels between the two
      subherds. Fecal glucocorticoid metabolite levels varied by season in both
      subherds, with levels in winter lower than during the other three seasons.
      Lamb:ewe ratios were not different between the control and treatment subherds at
      the end of summer 1999. In contrast, the treatment group had a lower lamb:ewe
      ratio at the end of summer 2000 despite having lower LPG. However, this result
      was attributed to lower ewe production, not lower lamb survival. The LPG levels
      were not correlated with FGM concentrations; instead, FGM levels might reflect
      normal seasonal patterns. Other factors, including contagious ecthyma, were more
      important for determining lamb mortality than LPG and FGM levels during our
      study. We suggest further experimental work over a longer duration to address
      these relationships.

PMID- 16107678
TI  - Leptospirosis in northern elephant seals (Mirounga angustirostris) stranded along
      the California coast.
AB  - Leptospirosis was identified in six northern elephant seals (Mirounga
      angustirostris) that were stranded in 1995 along the coast of California (USA).
      Histologic lesions in all seals included tubulointerstitial nephritis with
      tubular degeneration and necrosis. Infection was confirmed through identification
      of spirochetes using an immunohistochemical stain for Leptospira sp. antigens.
      One affected seal had an elevated titer to Leptospira interrogans serovar pomona.
      Four of the six seals developed leptospirosis during rehabilitation, and two
      seals had evidence of exposure in the wild. Potential sources of infection during
      rehabilitation include other elephant seals, California sea lions (Zalophus
      californianus), Pacific harbor seals (Phoca vitulina richardsii), or free-ranging
      wildlife. These results indicate that northern elephant seals are susceptible to
      leptospirosis and can develop disease both in the natural environment and in a
      rehabilitation setting.

PMID- 16107679
TI  - Kurloff cells in peripheral blood and organs of wild capybaras.
AB  - Peripheral blood and tissue from twenty-two free-ranging, hunter-killed capybaras
      (Hydrochaeris hydrochaeris) collected between December 1996 and April 1997 in
      Casanare, Colombia (5 degrees 58'N and 71 degrees 33'W), were examined by light
      microscopy for Kurloff cells (KCs). Kurloff cells were observed in the blood of
      one pregnant adult female, and in organs from all the animals, including spleen
      (21 of 22 animals), liver (18 of 21), lungs (13 of 21), ovary (8 of 11), uterus
      (7 of 10), bone marrow (13 of 20), kidney (8 of 22), adrenal gland (6 of 20), and
      lymph node (4 of 14). The anatomic distribution of the KC in the wild capybaras
      was similar to that of the guinea pig.

PMID- 16107680
TI  - Bovine tuberculosis in a free ranging red fox (Vulpes vulpes) from Donana
      National Park (Spain).
AB  - During 1997 and 1998, a survey of Iberian carnivores was conducted to study the
      epidemiology of bovine tuberculosis in the Donana National Park and surrounding
      areas in southwestern Spain. Post-mortem examinations were done on seven red
      foxes (Vulpes vulpes), two Egyptian mongoose (Herpestes ichneumon), one weasel
      (Mustela nivalis), two genets (Genetta genetta), one Iberian lynx (Lynx
      pardinus), one Eurasian badger (Meles meles), and two polecats (Mustela
      putorius). Lesions suggestive of bovine tuberculosis were not detected but, in
      culture, Mycobacterium bovis was isolated from the retropharyngeal lymph nodes of
      one adult male red fox. This is the first report of M. bovis infection in red fox
      in Spain.

PMID- 16107681
TI  - Molecular identification of a papilloma virus from cutaneous lesions of captive
      and free-ranging Florida manatees.
AB  - Cutaneous papillomatous lesions were biopsied from three captive Florida manatees
      (Trichechus manatus latirostris) at Homosassa Springs State Wildlife Park
      (HSSWP), Homosassa, Florida, USA, and from six free-ranging Florida manatees from
      Crystal and Homosassa rivers, Florida. Total DNA extracted from these lesions was
      assayed for the presence of papilloma virus genomes using the polymerase chain
      reaction (PCR) with primers that target the L1 capsid protein gene. The
      amplification generated DNA fragments 458 base pairs in length that encompassed a
      highly conserved domain within the L1 capsid protein and translated into
      identical polypeptides of 152 amino acids, suggesting the involvement of a single
      papilloma virus genotype. Multiple amino acid sequence and phylogenetic analyses
      of the L1 fragment indicated that the Florida manatee papilloma virus is a unique
      and quite distinct papillomavirus from other known papilloma viruses. The
      emergence of this new pathogen raises concerns about its potential impact on the
      already endangered Florida manatee.

PMID- 16107682
TI  - Eimeria species (Apicomplexa: Eimeriidae) infecting Eliomys quercinus in an
      Alpine habitat.
AB  - Coccidian parasites were detected in an Alpine population of the garden dormouse
      (Eliomys quercinus), and 55-82% of the fecal samples collected during a two-year
      study (2000 and 2002) contained one or two eimerian species. We report the
      presence of Eimeria myoxi and confirm for the first time the presence of Eimeria
      melanuri in the garden dormouse. These Eimeria species can be considered common
      parasites of the garden dormouse and the Asian garden dormouse. The high
      prevalence might be due to group hibernation by the dormice.

PMID- 16107683
TI  - Tuberculosis in Tanzanian wildlife.
AB  - Bovine tuberculosis, caused by Mycobacterium bovis, is a pathogen of growing
      concern in free-ranging wildlife in Africa, but little is known about the disease
      in Tanzanian wildlife. Here, we report the infection status of Mycobacterium
      bovis in a range of wildlife species sampled from protected areas in northern
      Tanzania. M. bovis was isolated from 11.1% (2/18) migratory wildebeest
      (Connochaetes taurinus) and 11.1% (1/9) topi (Damaliscus lunatus) sampled
      systematically in 2000 during a meat cropping program in the Serengeti ecosystem,
      and from one wildebeest and one lesser kudu (Tragelaphus imberbis) killed by
      sport hunters adjacent to Tarangire National Park. A tuberculosis antibody enzyme
      immunoassay (EIA) was used to screen serum samples collected from 184 Serengeti
      lions (Panthera leo) and 19 lions from Ngorongoro Crater sampled between 1985 and
      2000. Samples from 212 ungulates collected throughout the protected area network
      between 1998 and 2001 also were tested by EIA. Serological assays detected
      antibodies to M. bovis in 4% of Serengeti lions; one positive lion was sampled in
      1984. Antibodies were detected in one of 17 (6%) buffalo (Syncerus caffer) in
      Tarangire and one of 41 (2%) wildebeest in the Serengeti. This study confirms for
      the first time the presence of bovine tuberculosis in wildlife of northern
      Tanzania, but further investigation is required to assess the impact on wildlife
      populations and the role of different wildlife species in maintenance and
      transmission.

PMID- 16107684
TI  - Prevalence of Toxoplasma gondii and Neospora caninum in sika deer from eastern
      Hokkaido, Japan.
AB  - Brain and serum were collected from 120 and 12 free-ranging sika deer (Cervus
      nippon yesoensis), respectively, from six regions in eastern Hokkaido during
      controlled hunts in the autumn of 2003. Brains were tested for Neospora caninum
      and Toxoplasma gondii DNA by polymerase chain reaction (PCR) assays. Antibodies
      to Toxoplasma gondii were measured by means of a latex agglutination test. No
      brain tested positive for either type of DNA, and no antibody to Toxoplasma
      gondii was detected in serum, suggesting a low prevalence of infection with these
      organisms in free-ranging sika deer from eastern Hokkaido. Further examination of
      multiple tissues by PCR and serologic surveys will be necessary to confirm this.

PMID- 16107685
TI  - Cilia-associated respiratory (CAR) bacillus infection in adult red deer, chamois,
      and roe deer.
AB  - Cilia-associated respiratory (CAR) bacillus is an unclassified bacterium that
      colonizes the ciliated epithelium of airways in laboratory rats, laboratory mice,
      and laboratory and conventionally reared rabbits, cattle, goats, and pigs. Data
      on the prevalence of CAR bacillus infection in wild animals are lacking. The
      present study demonstrated the occurrence of the organism in wild red deer
      (Cervus elaphus hippelaphus), chamois (Rupicapra rupicapra), and roe deer
      (Capreolus capreolus) from the Val Fontana in northern Italy. Prevalence ranged
      from 26% for red deer to 56% for chamois, with a statistically significant
      negative correlation between CAR bacilli infection and the presence of lymphoid
      follicles.

PMID- 16107686
TI  - Mortality of geese as a result of collision with the ground.
AB  - Two incidents are reported in which groups of migrating wild geese were found
      dead in agricultural fields in southern Manitoba during spring. In each case, the
      birds died overnight and poisoning was suspected; however, the birds had lesions
      of severe traumatic injury. The first incident, in 1985, involved about 150
      lesser snow geese (Anser caerulescens caerulescens); the second, in 2003,
      involved 62 Canada geese (Branta canadensis). Both incidents occurred on dark,
      moonless nights. One possible explanation is that the birds became disoriented in
      a manner analogous to spatial disorientation described in aircraft pilots and
      flew as a flock directly into the earth. In the first incident, geese might have
      been frightened by sonic booms from aircraft; in the second, there was a
      thunderstorm with strong gusty winds in the area.

PMID- 16107687
TI  - Use of medetomidine-ketamine and atipamezole for reversible immobilization of
      free-ranging hog deer (Axis porcinus) captured in drive nets.
AB  - A combination of 0.05 mg/kg medetomidine and 1.5 mg/kg ketamine was used to
      immobilize nine adult free-ranging hog deer (Axis porcinus) captured in drive
      nets in the Royal Bardia National Park, Nepal, 22-23 February 2000. The drugs
      were administered intramuscularly from separate syringes and the mean time (+/
      SD) to complete immobilization was 4.6+/-1.0 min. Muscle relaxation was good and
      no major clinical side effects were seen. Mean values for physiologic parameters,
      recorded at 10-12 and 18-20 min after drug administration, were 40.6+/-0.5 and
      41.1+/-0.6 C, 87+/-5 and 84+/-4%, 107+/-16 and 113+/-16 beats/ min, and 46+/-9
      and 40+/-8 breaths/min for rectal temperature, SpO2, pulse rate, and respiratory
      rate, respectively. All animals received 0.25 mg/ kg atipamezole intramuscularly
      20-22 min after administration of medetomidine-ketamine and the mean time to
      coordinated running was 4.8+/-0.8 min. All animals survived for at least 5 mo
      post-capture. To reduce stress and to facilitate handling, medetomidine-ketamine
      and atipamezole are recommended for reversible immobilization of free-ranging hog
      deer captured in drive nets.

PMID- 16107689
TI  - Molecular genetic analysis of the yeast repressor Rfx1/Crt1 reveals a novel two
      step regulatory mechanism.
AB  - In Saccharomyces cerevisiae, the repressor Crt1 and the global corepressor Ssn6
      Tup1 repress the DNA damage-inducible ribonucleotide reductase (RNR) genes.
      Initiation of DNA damage signals causes the release of Crt1 and Ssn6-Tup1 from
      the promoter, coactivator recruitment, and derepression of transcription,
      indicating that Crt1 plays a crucial role in the switch between gene repression
      and activation. Here we have mapped the functional domains of Crt1 and identified
      two independent repression domains and a region required for gene activation. The
      N terminus of Crt1 is the major repression domain, it directly binds to the Ssn6
      Tup1 complex, and its repression activities are dependent upon Ssn6-Tup1 and
      histone deacetylases (HDACs). In addition, we identified a C-terminal repression
      domain, which is independent of Ssn6-Tup1 and HDACs and functions at native genes
      in vivo. Furthermore, we show that TFIID and SWI/SNF bind to a region within the
      N terminus of Crt1, overlapping with but distinct from the Ssn6-Tup1 binding and
      repression domain, suggesting that Crt1 may have activator functions. Crt1
      mutants were constructed to dissect its activator and repressor functions. All of
      the mutants were competent for repression of the DNA damage-inducible genes, but
      a majority were "derepression-defective" mutants. Further characterization of
      these mutants indicated that they are capable of receiving DNA damage signals and
      releasing the Ssn6-Tup1 complex from the promoter but are selectively impaired
      for TFIID and SWI/SNF recruitment. These results imply a two-step activation
      model of the DNA damage-inducible genes and that Crt1 functions as a signal
      dependent dual-transcription activator and repressor that acts in a transient
      manner.

PMID- 16107690
TI  - Phosphatidylinositol 3-kinase/Akt induced by erythropoietin renders the erythroid
      differentiation factor GATA-1 competent for TIMP-1 gene transactivation.
AB  - The contribution of erythropoietin to the differentiation of the red blood cell
      lineage remains elusive, and the demonstration of a molecular link between
      erythropoietin and the transcription of genes associated with erythroid
      differentiation is lacking. In erythroid cells, expression of the tissue
      inhibitor of matrix metalloproteinase (TIMP-1) is strictly dependent on
      erythropoietin. We report here that erythropoietin regulates the transcription of
      the TIMP-1 gene upon binding to its receptor in erythroid cells by triggering the
      activation of phosphatidylinositol 3-kinase (PI3K)/Akt. We found that Akt
      directly phosphorylates the transcription factor GATA-1 at serine 310 and that
      this site-specific phosphorylation is required for the transcriptional activation
      of the TIMP-1 promoter. This chain of events can be recapitulated in nonerythroid
      cells by transfection of the implicated molecular partners, resulting in the
      expression of the normally silent endogenous TIMP-1 gene. Conversely, TIMP-1
      secretion is profoundly decreased in erythroid cells from fetal livers of
      transgenic knock-in mice homozygous for a GATA(S310A) gene, which encodes a GATA
      1 mutant that cannot be phosphorylated at Ser(310). Furthermore, retrovirus
      mediated expression of GATA(S310A) into GATA-1(null)-derived embryonic stem cells
      decreases the rate of hemoglobinization by more than 50% compared to expressed
      wild-type GATA-1. These findings provide the first example of a chain of coupling
      mechanisms between the binding of erythropoietin to its receptor and GATA-1
      dependent gene expression.

PMID- 16107691
TI  - p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle
      arrest.
AB  - The ability of p53 to promote apoptosis and cell cycle arrest is believed to be
      important for its tumor suppression function. Besides activating the expression
      of cell cycle arrest and proapoptotic genes, p53 also represses a number of
      genes. Previous studies have shown an association between p53 activation and down
      regulation of c-myc expression. However, the mechanism and physiological
      significance of p53-mediated c-myc repression remain unclear. Here, we show that
      c-myc is repressed in a p53-dependent manner in various mouse and human cell
      lines and mouse tissues. Furthermore, c-myc repression is not dependent on the
      expression of p21(WAF1). Abrogating the repression of c-myc by ectopic c-myc
      expression interferes with the ability of p53 to induce G(1) cell cycle arrest
      and differentiation but enhances the ability of p53 to promote apoptosis. We
      propose that p53-dependent cell cycle arrest is dependent not only on the
      transactivation of cell cycle arrest genes but also on the transrepression of c
      myc. Chromatin immunoprecipitation assays indicate that p53 is bound to the c-myc
      promoter in vivo. We report that trichostatin A, an inhibitor of histone
      deacetylases, abrogates the ability of p53 to repress c-myc transcription. We
      also show that p53-mediated transcriptional repression of c-myc is accompanied by
      a decrease in the level of acetylated histone H4 at the c-myc promoter and by
      recruitment of the corepressor mSin3a. These data suggest that p53 represses c
      myc transcription through a mechanism that involves histone deacetylation.

PMID- 16107692
TI  - Role of Stat3 in regulating p53 expression and function.
AB  - Loss of p53 function by mutation is common in cancer. However, most natural p53
      mutations occur at a late stage in tumor development, and many clinically
      detectable cancers have reduced p53 expression but no p53 mutations. It remains
      to be fully determined what mechanisms disable p53 during malignant initiation
      and in cancers without mutations that directly affect p53. We show here that
      oncogenic signaling pathways inhibit the p53 gene transcription rate through a
      mechanism involving Stat3, which binds to the p53 promoter in vitro and in vivo.
      Site-specific mutation of a Stat3 DNA-binding site in the p53 promoter partially
      abrogates Stat3-induced inhibition. Stat3 activity also influences p53 response
      genes and affects UV-induced cell growth arrest in normal cells. Furthermore,
      blocking Stat3 in cancer cells up-regulates expression of p53, leading to p53
      mediated tumor cell apoptosis. As a point of convergence for many oncogenic
      signaling pathways, Stat3 is constitutively activated at high frequency in a wide
      diversity of cancers and is a promising molecular target for cancer therapy.
      Thus, repression of p53 expression by Stat3 is likely to have an important role
      in development of tumors, and targeting Stat3 represents a novel therapeutic
      approach for p53 reactivation in many cancers lacking p53 mutations.

PMID- 16107693
TI  - Vascular endothelial growth factor induces branching morphogenesis/tubulogenesis
      in renal epithelial cells in a neuropilin-dependent fashion.
AB  - Vascular endothelial growth factor (VEGF) is well characterized for its role in
      endothelial cell differentiation and vascular tube formation. Alternate splicing
      of the VEGF gene in mice results in various VEGF-A isoforms, including VEGF-121
      and VEGF-165. VEGF-165 is the most abundant isoform in the kidney and has been
      implicated in glomerulogenesis. However, its role in the tubular epithelium is
      not known. We demonstrate that VEGF-165 but not VEGF-121 induces single-cell
      branching morphogenesis and multicellular tubulogenesis in mouse renal tubular
      epithelial cells and that these morphogenic effects require activation of the
      phosphatidylinositol 3-kinase (PI 3-K) and, to a lesser degree, the extracellular
      signal-regulated kinase and protein kinase C signaling pathways. Further, VEGF
      165-stimulated sheet migration is dependent only on PI 3-K signaling. These
      morphogenic effects of VEGF-165 require activation of both VEGF receptor 2 (VEGFR
      2) and neuropilin-1 (Nrp-1), since neutralizing antibodies to either of these
      receptors or the addition of semaphorin 3A (which blocks VEGF-165 binding to Nrp
      1) prevents the morphogenic response and the phosphorylation of VEGFR-2 along
      with the downstream signaling. We thus conclude that in addition to endothelial
      vasculogenesis, VEGF can induce renal epithelial cell morphogenesis in a Nrp-1
      dependent fashion.

PMID- 16107694
TI  - Pam17 is required for architecture and translocation activity of the
      mitochondrial protein import motor.
AB  - Import of mitochondrial matrix proteins involves the general translocase of the
      outer membrane and the presequence translocase of the inner membrane. The
      presequence translocase-associated motor (PAM) drives the completion of
      preprotein translocation into the matrix. Five subunits of PAM are known: the
      preprotein-binding matrix heat shock protein 70 (mtHsp70), the nucleotide
      exchange factor Mge1, Tim44 that directs mtHsp70 to the inner membrane, and the
      membrane-bound complex of Pam16-Pam18 that regulates the ATPase activity of
      mtHsp70. We have identified a sixth motor subunit. Pam17 (encoded by the open
      reading frame YKR065c) is anchored in the inner membrane and exposed to the
      matrix. Mitochondria lacking Pam17 are selectively impaired in the import of
      matrix proteins and the generation of an import-driving activity of PAM. Pam17 is
      required for formation of a stable complex between the cochaperones Pam16 and
      Pam18 and promotes the association of Pam16-Pam18 with the presequence
      translocase. Our findings suggest that Pam17 is required for the correct
      organization of the Pam16-Pam18 complex and thus contributes to regulation of
      mtHsp70 activity at the inner membrane translocation site.

PMID- 16107695
TI  - Severe adenine starvation activates Ty1 transcription and retrotransposition in
      Saccharomyces cerevisiae.
AB  - Ty1 retrotransposons of the yeast Saccharomyces cerevisiae are activated by
      different kinds of stress. Here we show that Ty1 transcription is stimulated
      under severe adenine starvation conditions. The Bas1 transcriptional activator,
      responsible for the induction of genes of the de novo AMP biosynthesis pathway
      (ADE) in the absence of adenine, is not involved in this response. Activation
      occurs mainly on Ty1 elements, whose expression is normally repressed by
      chromatin and is suppressed in a hta1-htb1Delta mutant that alters chromatin
      structure. Activation is also abolished in a snf2Delta mutant. Several regions of
      the Ty1 promoter are necessary to achieve full activation, suggesting that full
      integrity of the promoter sequences might be important for activation. Together,
      these observations are consistent with a model in which the activation mechanism
      involves chromatin remodeling at Ty1 promoters. The consequence of Ty1
      transcriptional activation in response to adenine starvation is an increase in
      Ty1 cDNA levels and a relief of Ty1 dormancy. The retrotransposition of four
      native Ty1 elements increases in proportion to their increase in transcription.
      Implications for the regulation of Ty1 mobility by changes in Ty1 mRNA levels are
      discussed.

PMID- 16107696
TI  - NF-kappaB-repressing factor inhibits elongation of human immunodeficiency virus
      type 1 transcription by DRB sensitivity-inducing factor.
AB  - Human immunodeficiency virus type 1 (HIV-1) is able to establish a latent
      infection during which the integrated provirus remains transcriptionally silent.
      In response to specific stimuli, the HIV-1 long terminal repeat (LTR) is highly
      activated, enhancing both transcriptional initiation and elongation. Here, we
      have identified a specific binding sequence of the nuclear NF-kappaB-repressing
      factor (NRF) within the HIV-1 LTR. The aim of this work was to define the role of
      NRF in regulating the LTR. Our data show that the endogenous NRF is required for
      transcriptional activation of the HIV-1 LTR in stimulated cells. In unstimulated
      cells, however, NRF inhibits HIV-1 LTR activity at the level of transcription
      elongation. Binding of NRF to the LTR in unstimulated cells prevents recruitment
      of elongation factor DRB sensitivity-inducing factor and formation of processive
      elongation complexes by hyperphosphorylated RNA polymerase II. Our data suggest
      that NRF interrupts the regulatory coupling of LTR binding factors and
      transcription elongation events. This inhibitory mechanism might contribute to
      transcriptional quiescence of integrated HIV-1 provirus.

PMID- 16107697
TI  - ATPase/helicase activities of p68 RNA helicase are required for pre-mRNA splicing
      but not for assembly of the spliceosome.
AB  - We have previously demonstrated that p68 RNA helicase, as an essential human
      splicing factor, acts at the U1 snRNA and 5' splice site (5'ss) duplex in the pre
      mRNA splicing process. To further analyze the function of p68 in the spliceosome,
      we generated two p68 mutants (motif V, RGLD to LGLD, and motif VI, HRIGR to
      HLIGR). ATPase and RNA unwinding assays demonstrated that the mutations abolished
      the RNA-dependent ATPase activity and RNA unwinding activity. The function of p68
      in the spliceosome was abolished by the mutations, and the mutations also
      inhibited the dissociation of U1 from the 5'ss, while the mutants still
      interacted with the U1-5'ss duplex. Interestingly, the nonactive p68 mutants did
      not prevent the transition from prespliceosome to the spliceosome. The data
      suggested that p68 RNA helicase might actively unwind the U1-5'ss duplex. The
      protein might also play a role in the U4.U6/U5 addition, which did not require
      the ATPase and RNA unwinding activities of p68. In addition, we present evidence
      here to demonstrate the functional role of p68 RNA helicase in the pre-mRNA
      splicing process in vivo. Our experiments also showed that p68 interacted with
      unspliced but not spliced mRNA in vivo.

PMID- 16107698
TI  - A mutation in Dbf4 motif M impairs interactions with DNA replication factors and
      confers increased resistance to genotoxic agents.
AB  - Dbf4/Cdc7 is required for DNA replication in Saccharomyces cerevisiae and appears
      to be a target in the S-phase checkpoint. Previously, a 186-amino-acid Dbf4
      region that mediates interactions with both the origin recognition complex and
      Rad53 was identified. We now show this domain also mediates the association
      between Dbf4 and Mcm2, a key Dbf4/Cdc7 phosphorylation target. Two conserved
      sequences, the N and M motifs, have been identified within this Dbf4 region.
      Removing motif M (Dbf4DeltaM) impairs the ability of Dbf4 to support normal cell
      cycle progression and abrogates the Dbf4-Mcm2 association but has no effect on
      the Dbf4-Rad53 interaction. In contrast, deleting motif N (Dbf4DeltaN) does not
      affect the essential function of Dbf4, disrupts the Dbf4-Rad53 interaction,
      largely preserves the Dbf4-Mcm2 association, and renders the cells hypersensitive
      to genotoxic agents. Surprisingly, Dbf4DeltaM interacts strongly with Orc2, while
      Dbf4DeltaN does not. The DBF4 allele dna52-1 was cloned and sequenced, revealing
      a single point mutation within the M motif. This mutant is unable to maintain
      interactions with either Mcm2 or Orc2 at the semipermissive temperature of 30
      degrees C, while the interaction with Rad53 is preserved. Furthermore, this
      mutation confers increased resistance to genotoxic agents, which we propose is
      more likely due to a role for Dbf4 in the resumption of fork progression
      following checkpoint-induced arrest than prevention of late origin firing. Thus,
      the alteration of the M motif may facilitate the role of Dbf4 as a checkpoint
      target.

PMID- 16107699
TI  - Mammalian peptidylglycine alpha-amidating monooxygenase mRNA expression can be
      modulated by the La autoantigen.
AB  - Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the
      COOH-terminal alpha-amidation of peptidylglycine substrates, yielding amidated
      products. We have previously reported a putative regulatory RNA binding protein
      (PAM mRNA-BP) that binds specifically to the 3' untranslated region (UTR) of PAM
      mRNA. Here, the PAM mRNA-BP was isolated and revealed to be La protein using
      affinity purification onto a 3' UTR PAM RNA, followed by tandem mass spectrometry
      identification. We determined that the core binding sequence is approximately 15
      nucleotides (nt) long and is located 471 nt downstream of the stop codon.
      Moreover, we identified the La autoantigen as a protein that specifically binds
      the 3' UTR of PAM mRNA in vivo and in vitro. Furthermore, La protein
      overexpression caused a nuclear retention of PAM mRNAs and resulted in the down
      regulation of endogenous PAM activity. Most interestingly, the nuclear retention
      of PAM mRNA is lost upon expressing the La proteins that lack a conserved nuclear
      retention element, suggesting a direct association between PAM mRNA and La
      protein in vivo. Reporter assays using a chimeric mRNA that combined luciferase
      and the 3' UTR of PAM mRNA demonstrated a decrease of the reporter activity due
      to an increase in the nuclear localization of reporter mRNAs, while the deletion
      of the 15-nt La binding site led to their clear-cut cytoplasmic relocalization.
      The results suggest an important role for the La protein in the modulation of PAM
      expression, possibly by mechanisms that involve a nuclear retention and perhaps a
      processing of pre-PAM mRNA molecules.

PMID- 16107700
TI  - Activation of hepatitis B virus S promoter by a cell type-restricted IRE1
      dependent pathway induced by endoplasmic reticulum stress.
AB  - IRE1-alpha is an integral membrane protein of the endoplasmic reticulum (ER) that
      is a key sensor in the cellular transcriptional response to stress in the ER.
      Upon induction of ER stress, IRE1-alpha is activated, resulting in the synthesis
      of the active form of the transcription factor XBP1 via IRE1-mediated splicing of
      its mRNA. In this report, we have examined the role of IRE1-alpha and XBP1 in
      activation of the hepatitis B virus S promoter by ER stress. Cotransfection
      experiments revealed that overexpression of either IRE1-alpha or XBP1 activated
      this promoter. Conversely, cotransfected dominant-negative IRE1-alpha or small
      interfering RNA directed against XBP1 decreased the activation of the S promoter
      by ER stress, confirming an important role for the IRE1-alpha/XBP1 signaling
      pathway in activation of the S promoter. However, XBP1 does not bind directly to
      the S promoter; rather, a novel S promoter-binding complex that does not contain
      XBP1 is induced in cells undergoing ER stress in an XBP1-dependent manner. This
      complex, as well as transcriptional activation of the S promoter, is induced by
      ER stress in hepatocytes but not in fibroblasts, despite the presence of active
      XBP1 in the latter. Thus, the hepatitis B virus S promoter responds to a novel,
      cell type-restricted transcriptional pathway downstream of IRE1-alpha and XBP1.

PMID- 16107701
TI  - Human histone chaperone nucleophosmin enhances acetylation-dependent chromatin
      transcription.
AB  - Histone chaperones are a group of proteins that aid in the dynamic chromatin
      organization during different cellular processes. Here, we report that the human
      histone chaperone nucleophosmin interacts with the core histones H3, H2B, and H4
      but that this histone interaction is not sufficient to confer the chaperone
      activity. Significantly, nucleophosmin enhances the acetylation-dependent
      chromatin transcription and it becomes acetylated both in vitro and in vivo.
      Acetylation of nucleophosmin and the core histones was found to be essential for
      the enhancement of chromatin transcription. The acetylated NPM1 not only shows an
      increased affinity toward acetylated histones but also shows enhanced histone
      transfer ability. Presumably, nucleophosmin disrupts the nucleosomal structure in
      an acetylation-dependent manner, resulting in the transcriptional activation.
      These results establish nucleophosmin (NPM1) as a human histone chaperone that
      becomes acetylated, resulting in the enhancement of chromatin transcription.

PMID- 16107702
TI  - Mechanism of von Hippel-Lindau protein-mediated suppression of nuclear factor
      kappa B activity.
AB  - Biallelic inactivating mutations of the von Hippel-Lindau tumor suppressor gene
      (VHL) are a hallmark of clear cell renal cell carcinoma (CCRCC), the most common
      histologic subtype of RCC. Biallelic VHL loss results in accumulation of hypoxia
      inducible factor alpha (HIFalpha). Restoring expression of the wild-type protein
      encoded by VHL (pVHL) in tumors with biallelic VHL inactivation (VHL(-)(/)(-))
      suppresses tumorigenesis, and pVHL-mediated degradation of HIFalpha is necessary
      and sufficient for VHL-mediated tumor suppression. The downstream targets of
      HIFalpha that promote renal carcinogenesis have not been completely elucidated.
      Recently, VHL loss was shown to activate nuclear factor kappa B (NF-kappaB), a
      family of transcription factors that promotes tumor growth. Here we show that VHL
      loss drives NF-kappaB activation by resulting in HIFalpha accumulation, which
      induces expression of transforming growth factor alpha, with consequent
      activation of an epidermal growth factor receptor/phosphatidylinositol-3-OH
      kinase/protein kinase B (AKT)/IkappaB-kinase alpha/NF-kappaB signaling cascade.
      We also show that components of this signaling pathway promote the growth of VHL(
      )(/)(-) tumor cells. Members of this pathway represent viable drug targets in
      VHL(-)(/)(-) tumors, such as those associated with CCRCC.

PMID- 16107703
TI  - The transmembrane adapter protein SIT regulates thymic development and peripheral
      T-cell functions.
AB  - SIT is a transmembrane adapter protein that modulates signals emanating from the
      T-cell receptor (TCR). Here, we have used gene-targeted mice to assess the role
      of SIT for T-cell development and peripheral T-cell functions. SIT(-/-) double
      positive thymocytes show an upregulation of the activation markers CD5 and CD69,
      suggesting that SIT negatively regulates TCR-mediated signals at the CD4(+)
      CD8(+) stage of thymic development. This assumption is further supported by the
      observation that in female H-Y TCR transgenic mice, positive selection is
      enhanced and even converted to negative selection. Similarly, mature peripheral T
      cells are hyperresponsive towards TCR-mediated stimuli and produce larger amounts
      of T-helper 1 (TH1) cytokines, and SIT-deficient mice show an increased
      susceptibility to develop experimental autoimmune encephalomyelitis, a mouse
      model of multiple sclerosis. These results demonstrate that SIT is a critical
      negative regulator of TCR-mediated signaling and finely tunes the signals
      required for thymic selection and peripheral T-cell activation.

PMID- 16107704
TI  - Disruption of murine Mus81 increases genomic instability and DNA damage
      sensitivity but does not promote tumorigenesis.
AB  - The Mus81-Eme1 endonuclease is implicated in the efficient rescue of broken
      replication forks in Saccharomyces cerevisiae and Schizosaccharomyces pombe. We
      have used gene targeting to study the function of the Mus81-Eme1 endonuclease in
      mammalian cells. Mus81-deficient mice develop normally and are fertile.
      Surprisingly, embryonic fibroblasts from Mus81(-/-) animals fail to proliferate
      in vitro. This proliferation defect can be rescued by expression of the
      papillomavirus E6 protein that promotes degradation of p53. When grown in
      culture, Mus81(-/-) cells have elevated levels of DNA damage, acquire chromosomal
      aberrations, and are hypersensitive to agents that generate DNA cross-links. In
      contrast to the situation in yeast, murine Mus81 is not required for replication
      restart following camptothecin treatment. Mus81(-/-) mice and cells are
      hypersensitive to DNA cross-linking agents. Cross-link-induced double-strand
      break formation is normal in Mus81(-/-) cells, but the resolution of repair
      intermediates is not. The persistence of Rad51 foci in Mus81(-/-) cells suggests
      that Mus81 acts at a late step in the repair of cross-link-induced lesions.
      Despite these defects, Mus81(-/-) mice do not show increased predisposition to
      lymphoma or any other malignancy in the first year of life.

PMID- 16107705
TI  - ELAV multimerizes on conserved AU4-6 motifs important for ewg splicing
      regulation.
AB  - ELAV is a gene-specific regulator of alternative pre-mRNA processing in
      Drosophila neurons. Since ELAV/Hu proteins preferentially bind to AU-rich regions
      that are generally abundant in introns and untranslated regions, it has not been
      clear how gene specificity is achieved. Here we used a combination of in vitro
      biochemical experiments together with phylogenetic comparisons and in vivo
      analysis of Drosophila transgenes to study ELAV binding to the last ewg intron
      and splicing regulation. In vitro binding studies of ELAV show that ELAV
      multimerizes on the ewg binding site and forms a defined and saturable complex.
      Further, sizing of the ELAV-RNA complex and a series of titration experiments
      indicate that ELAV forms a dodecameric complex on 135 nucleotides in the last ewg
      intron. Analysis of the substrate RNA requirements for ELAV binding and complex
      formation indicates that a series of AU(4-6) motifs spread over the entire
      binding site are important, but not a strictly defined sequence element. The
      importance of AU(4-6) motifs, but not spacing between them, is further supported
      by evolutionary conservation in several melanogaster species subgroups. Finally,
      using transgenes we demonstrate in fly neurons that ELAV-mediated regulation of
      ewg intron 6 splicing requires several AU(4-6) motifs and that introduction of
      spacer sequence between conserved AU(4-6) motifs has a minimal effect on
      splicing. Collectively, our results suggest that ELAV multimerization and binding
      to multiple AU(4-6) motifs contribute to target RNA recognition and processing in
      a complex cellular environment.

PMID- 16107706
TI  - The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates adipogenesis.
AB  - Mitogen-activated protein kinase pathways are implicated in the regulation of
      cell differentiation, although their precise roles in many differentiation
      programs remain elusive. The Raf/MEK/extracellular signal-regulated kinase (ERK)
      kinase cascade has been proposed to both promote and inhibit adipogenesis. Here,
      we titrate expression of the molecular scaffold kinase suppressor of Ras 1 (KSR1)
      to regulate signaling through the Raf/MEK/ERK/p90 ribosomal S6 kinase (RSK)
      kinase cascade and show how it determines adipogenic potential. Deletion of KSR1
      prevents adipogenesis in vitro, which can be rescued by introduction of low
      levels of KSR1. Appropriate levels of KSR1 coordinate ERK and RSK activation with
      C/EBPbeta synthesis leading to the phosphorylation and stabilization of C/EBPbeta
      at the precise moment it is required within the adipogenic program. Elevated
      levels of KSR1 expression, previously shown to enhance cell proliferation,
      promote high, sustained ERK activation that phosphorylates and inhibits
      peroxisome proliferator-activated receptor gamma, inhibiting adipogenesis.
      Titration of KSR1 expression reveals how a molecular scaffold can modulate the
      intensity and duration of signaling emanating from a single pathway to dictate
      cell fate.

PMID- 16107708
TI  - Structural characterization of the histone variant macroH2A.
AB  - macroH2A is an H2A variant with a highly unusual structural organization. It has
      a C-terminal domain connected to the N-terminal histone domain by a linker.
      Crystallographic and biochemical studies show that changes in the L1 loop in the
      histone fold region of macroH2A impact the structure and potentially the function
      of nucleosomes. The 1.6-A X-ray structure of the nonhistone region reveals an
      alpha/beta fold which has previously been found in a functionally diverse group
      of proteins. This region associates with histone deacetylases and affects the
      acetylation status of nucleosomes containing macroH2A. Thus, the unusual domain
      structure of macroH2A integrates independent functions that are instrumental in
      establishing a structurally and functionally unique chromatin domain.

PMID- 16107707
TI  - Differential phosphorylation controls Maskin association with eukaryotic
      translation initiation factor 4E and localization on the mitotic apparatus.
AB  - Several cytoplasmic polyadenylation element (CPE)-containing mRNAs that are
      repressed in Xenopus oocytes become active during meiotic maturation. A group of
      factors that are anchored to the CPE are responsible for this repression and
      activation. Two of the most important are CPEB, which binds directly to the CPE,
      and Maskin, which associates with CPEB. In oocytes, Maskin also binds eukaryotic
      translation initiation factor 4E (eIF4E), an interaction that excludes eIF4G and
      prevents formation of the eIF4F initiation complex. When the oocytes are
      stimulated to reenter the meiotic divisions (maturation), CPEB promotes
      cytoplasmic polyadenylation. The newly elongated poly(A) tail becomes bound by
      poly(A) binding protein (PABP), which in turn binds eIF4G and helps it displace
      Maskin from eIF4E, thereby inducing translation. Here we show that Maskin
      undergoes several phosphorylation events during oocyte maturation, some of which
      are important for its dissociation from eIF4E and translational activation of CPE
      containing mRNA. These sites are T58, S152, S311, S343, S453, and S638 and are
      phosphorylated by cdk1. Mutation of these sites to alanine alleviates the cdk1
      induced dissociation of Maskin from eIF4E. Prior to maturation, Maskin is
      phosphorylated on S626 by protein kinase A. While this modification has no
      detectable effect on translation during oocyte maturation, it is critical for
      this protein to localize on the mitotic apparatus in somatic cells. These results
      show that Maskin activity and localization is controlled by differential
      phosphorylation.

PMID- 16107709
TI  - Cooperation of the Cockayne syndrome group B protein and poly(ADP-ribose)
      polymerase 1 in the response to oxidative stress.
AB  - Cockayne syndrome (CS) is a rare genetic disorder characterized as a segmental
      premature-aging syndrome. The CS group B (CSB) protein has previously been
      implicated in transcription-coupled repair, transcriptional elongation, and
      restoration of RNA synthesis after DNA damage. Recently, evidence for a role of
      CSB in base excision repair of oxidative DNA lesions has accumulated. In our
      search to understand the molecular function of CSB in this process, we identify a
      physical and functional interaction between CSB and poly(ADP-ribose) polymerase-1
      (PARP-1). PARP-1 is a nuclear enzyme that protects the integrity of the genome by
      responding to oxidative DNA damage and facilitating DNA repair. PARP-1 binds to
      single-strand DNA breaks which activate the catalytic ability of PARP-1 to add
      polymers of ADP-ribose to various proteins. We find that CSB is present at sites
      of activated PARP-1 after oxidative stress, identify CSB as a new substrate of
      PARP-1, and demonstrate that poly(ADP-ribosyl)ation of CSB inhibits its DNA
      dependent ATPase activity. Furthermore, we find that CSB-deficient cell lines are
      hypersensitive to inhibition of PARP. Our results implicate CSB in the PARP-1
      poly(ADP-ribosyl)ation response after oxidative stress and thus suggest a novel
      role of CSB in the cellular response to oxidative damage.

PMID- 16107710
TI  - The nuclear form of phospholipid hydroperoxide glutathione peroxidase is a
      protein thiol peroxidase contributing to sperm chromatin stability.
AB  - The selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) is
      regarded as the major molecular target of selenodeficiency in rodents, accounting
      for most of the histopathological and structural abnormalities of testicular
      tissue and male germ cells. PHGPx exists as a cytosolic form, mitochondrial form,
      and nuclear form (nPHGPx) predominantly expressed in late spermatids and
      spermatozoa. Here, we demonstrate that mice with a targeted deletion of the
      nPHGPx gene were, unlike mice with the full knockout (KO) of PHGPx, not only
      viable but also, surprisingly, fully fertile. While both morphological analysis
      of testis and epididymis and sperm parameter measurements did not show any
      apparent abnormality, toluidine blue and acridine orange stainings of spermatozoa
      indicated defective chromatin condensation in the KO sperm isolated from the
      caput epididymis. Furthermore, upon drying and hydrating, KO sperm exhibited a
      significant proportion of morphologically abnormal heads. Monobromobimane
      labeling and protein-free thiol titration revealed significantly less extensive
      oxidation in the cauda epididymis when compared to that in the wild type. We
      conclude that nPHGPx, by acting as a protein thiol peroxidase in vivo,
      contributes to the structural stability of sperm chromatin.

PMID- 16107711
TI  - FoxO1a-cyclic GMP-dependent kinase I interactions orchestrate myoblast fusion.
AB  - The regulatory circuits that orchestrate mammalian myoblast cell fusion during
      myogenesis are poorly understood. The transcriptional activity of FoxO1a directly
      regulates this process, yet the molecular mechanisms governing FoxO1a activity
      during muscle cell differentiation remain unknown. Here we show an autoregulatory
      loop in which FoxO1a directly activates transcription of the cyclic GMP-dependent
      protein kinase I (cGKI) gene and where the ensuing cGKI activity phosphorylates
      FoxO1a and abolishes its DNA binding activity. These findings establish the
      FoxO1a-to-cGKI pathway as a novel feedback loop that allows the precise tuning of
      myoblast fusion. Interestingly, this pathway appears to operate independently of
      muscle cell differentiation programs directed by myogenic transcription factors.

PMID- 16107712
TI  - Reduction of spermatogenesis but not fertility in Creb3l4-deficient mice.
AB  - Creb3l4 belongs to the CREB/ATF family of transcription factors that are involved
      in mediating transcription in response to intracellular signaling. This study
      shows that Creb3l4 is expressed at low levels in all organs and in different
      stages of embryogenesis but is present at very high levels in the testis,
      particularly in postmeiotic male germ cells. In contrast to CREB3L4 in the human
      prostate, of which specific expression was detected, Creb3l4 transcripts in the
      mouse prostate could be detected only by RT-PCR. To identify the physiological
      function of Creb3l4, the murine gene was inactivated by replacement with the gene
      encoding green fluorescent protein. Surprisingly, Creb3l4-deficient mice were
      born at expected ratios, were healthy, and displayed normal long-term survival
      rates. Despite a significant reduction in the number of spermatozoa in the
      epididymis of Creb3l4(-)(/)(-) mice, the breeding of mutant males with wild-type
      females was productive and the average litter size was not significantly altered
      in comparison to wild-type littermates. Further analyses revealed that the
      seminiferous tubules of Creb3l4(-)(/)(-) mice contained all of the developmental
      stages, though there was evidence for increased apoptosis of meiotic/postmeiotic
      germ cells. These results suggest that Creb3l4 plays a role in male germ cell
      development, but its loss is insufficient to completely compromise the production
      of spermatozoa.

PMID- 16107713
TI  - Role of the mammalian RNA polymerase II C-terminal domain (CTD) nonconsensus
      repeats in CTD stability and cell proliferation.
AB  - The C-terminal domain (CTD) of mammalian RNA polymerase II (Pol II) consists of
      52 repeats of the consensus heptapeptide YSPTSPS and links transcription to the
      processing of pre-mRNA. The length of the CTD and the number of repeats diverging
      from the consensus sequence have increased through evolution, but their
      functional importance remains unknown. Here, we show that the deletion of repeats
      1 to 3 or 52 leads to cleavage and degradation of the CTD from Pol II in vivo.
      Including these repeats, however, allowed the construction of stable, synthetic
      CTDs. To our surprise, polymerases consisting of just consensus repeats could
      support normal growth and viability of cells. We conclude that all other
      nonconsensus CTD repeats are dispensable for the transcription and pre-mRNA
      processing of genes essential for proliferation.

PMID- 16107714
TI  - Eukaryotic translational coupling in UAAUG stop-start codons for the bicistronic
      RNA translation of the non-long terminal repeat retrotransposon SART1.
AB  - Most eukaryotic cellular mRNAs are monocistronic; however, many retroviruses and
      long terminal repeat (LTR) retrotransposons encode multiple proteins on a single
      RNA transcript using ribosomal frameshifting. Non-long terminal repeat (non-LTR)
      retrotransposons are considered the ancestor of LTR retrotransposons and
      retroviruses, but their translational mechanism of bicistronic RNA remains
      unknown. We used a baculovirus expression system to produce a large amount of the
      bicistronic RNA of SART1, a non-LTR retrotransposon of the silkworm, and were
      able to detect the second open reading frame protein (ORF2) by Western blotting.
      The ORF2 protein was translated as an independent protein, not as an ORF1-ORF2
      fusion protein. We revealed by mutagenesis that the UAAUG overlapping stop-start
      codon and the downstream RNA secondary structure are necessary for efficient ORF2
      translation. Increasing the distance between the ORF1 stop codon and the ORF2
      start codon decreased translation efficiency. These results are different from
      the eukaryotic translation reinitiation mechanism represented by the yeast GCN4
      gene, in which the probability of reinitiation increases as the distance between
      the two ORFs increases. The translational mechanism of SART1 ORF2 is analogous to
      translational coupling observed in prokaryotes and viruses. Our results indicate
      that translational coupling is a general mechanism for bicistronic RNA
      translation.

PMID- 16107715
TI  - Dual functions of the steroid hormone receptor coactivator 3 in modulating
      resistance to thyroid hormone.
AB  - Mutations of the thyroid hormone receptor beta (TRbeta) gene cause resistance to
      thyroid hormone (RTH). RTH is characterized by increased serum thyroid hormone
      associated with nonsuppressible thyroid-stimulating hormone (TSH) and impaired
      growth. It is unclear how the actions of TRbeta mutants are modulated in vivo to
      affect the manifestation of RTH. Using a mouse model of RTH that harbors a
      knockin mutation of the TRbeta gene (TRbetaPV mouse), we investigated the effect
      of the steroid hormone receptor coactivator 3 (SRC-3) on RTH. In TRbetaPV mice
      deficient in SRC-3, dysfunction of the pituitary-thyroid axis and
      hypercholesterolemia was lessened, but growth impairment of RTH was worsened. The
      lessened dysfunction of the pituitary-thyroid axis was attributed to a
      significant decrease in growth of the thyroid and pituitary. Serum insulin-like
      growth factor 1 (IGF-1) was further reduced in TRbetaPV mice deficient in SRC-3.
      This effect led to reduced signaling of the IGF-1/phosphatidylinositol 3-kinase
      (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway that is known to mediate
      cell growth and proliferation. Thus, SRC-3 modulates RTH by at least two
      mechanisms, one via its role as a receptor coregulator and the other via its
      growth regulatory role through the IGF-1/PI3K/AKT/mTOR signaling.

PMID- 16107716
TI  - Immunoisolaton of the yeast Golgi subcompartments and characterization of a novel
      membrane protein, Svp26, discovered in the Sed5-containing compartments.
AB  - The Golgi apparatus consists of a set of vesicular compartments which are
      distinguished by their marker proteins. These compartments are physically
      separated in the Saccharomyces cerevisiae cell. To characterize them extensively,
      we immunoisolated vesicles carrying either of the SNAREs Sed5 or Tlg2, the
      markers of the early and late Golgi compartments, respectively, and analyzed the
      membrane proteins. The composition of proteins was mostly consistent with the
      position of each compartment in the traffic. We found six uncharacterized but
      evolutionarily conserved proteins and named them Svp26 (Sed5 compartment vesicle
      protein of 26 kDa), Tvp38, Tvp23, Tvp18, Tvp15 (Tlg2 compartment vesicle proteins
      of 38, 23, 18, and 15 kDa), and Gvp36 (Golgi vesicle protein of 36 kDa). The
      localization of Svp26 in the early Golgi compartment was confirmed by microscopic
      and biochemical means. Immunoprecipitation indicated that Svp26 binds to itself
      and a Golgi mannosyltransferase, Ktr3. In the absence of Svp26, a considerable
      portion of Ktr3 was mislocalized in the endoplasmic reticulum. Our data suggest
      that Svp26 has a novel role in retention of a subset of membrane proteins in the
      early Golgi compartments.

PMID- 16107717
TI  - NRAGE mediates p38 activation and neural progenitor apoptosis via the bone
      morphogenetic protein signaling cascade.
AB  - Understanding the molecular events that govern neural progenitor lineage
      commitment, mitotic arrest, and differentiation into functional progeny are
      germane to our understanding of neocortical development. Members of the family of
      bone morphogenetic proteins (BMPs) play pivotal roles in regulating neural
      differentiation and apoptosis during neurogenesis through combined actions
      involving Smad and TAK1 activation. We demonstrate that BMP signaling is required
      for the induction of apoptosis of neural progenitors and that NRAGE is a
      mandatory component of the signaling cascade. NRAGE possesses the ability to bind
      and function with the TAK1-TAB1-XIAP complex facilitating the activation of p38.
      Disruption of NRAGE or any other member of the noncanonical signaling cascaded is
      sufficient to block p38 activation and thus the proapoptotic signals generated
      through BMP exposure. The function of NRAGE is independent of Smad signaling, but
      the introduction of a dominant-negative Smad5 also rescues neural progenitor
      apoptosis, suggesting that both canonical and noncanonical pathways can converge
      and regulate BMP-mediated apoptosis. Collectively, these results establish NRAGE
      as an integral component in BMP signaling and clarify its role during neural
      progenitor development.

PMID- 16107718
TI  - The Arabidopsis Pot1 and Pot2 proteins function in telomere length homeostasis
      and chromosome end protection.
AB  - Pot1 (protection of telomeres 1) is a single-stranded telomere binding protein
      that is essential for chromosome end protection and telomere length homeostasis.
      Arabidopsis encodes two Pot1-like proteins, dubbed AtPot1 and AtPot2. Here we
      show that telomeres in transgenic plants expressing a truncated AtPot1 allele
      lacking the N-terminal oligonucleotide/oligosaccharide binding fold (P1DeltaN)
      are 1 to 1.5 kb shorter than in the wild type, suggesting that AtPot1 contributes
      to the positive regulation of telomere length control. In contrast, telomere
      length is unperturbed in plants expressing the analogous region of AtPot2. A
      strikingly different phenotype is observed in plants overexpressing the AtPot2 N
      terminus (P2DeltaC) but not the corresponding region in AtPot1. Although bulk
      telomeres in P2DeltaC mutants are 1 to 2 kb shorter than in the wild type, these
      plants resemble late-generation telomerase-deficient mutants with severe growth
      defects, sterility, and massive genome instability, including bridged chromosomes
      and aneuploidy. The genome instability associated with P2DeltaC mutants implies
      that AtPot2 contributes to chromosome end protection. Thus, Arabidopsis has
      evolved two Pot genes that function differently in telomere biology. These
      findings provide unanticipated information about the evolution of single-stranded
      telomere binding proteins.

PMID- 16107719
TI  - Epidermal growth factor receptor dimerization and activation require ligand
      induced conformational changes in the dimer interface.
AB  - Structural studies have shown that ligand-induced epidermal growth factor
      receptor (EGFR) dimerization involves major domain rearrangements that expose a
      critical dimerization arm. However, simply exposing this arm is not sufficient
      for receptor dimerization, suggesting that additional ligand-induced dimer
      contacts are required. To map these contributions to the dimer interface, we
      individually mutated each contact suggested by crystallographic studies and
      analyzed the effects on receptor dimerization, activation, and ligand binding. We
      find that domain II contributes >90% of the driving energy for dimerization of
      the extracellular region, with domain IV adding little. Within domain II, the
      dimerization arm forms much of the dimer interface, as expected. However, a loop
      from the sixth disulfide-bonded module (immediately C-terminal to the
      dimerization arm) also makes a critical contribution. Specific ligand-induced
      conformational changes in domain II are required for this loop to contribute to
      receptor dimerization, and we identify a set of ligand-induced intramolecular
      interactions that appear to be important in driving these changes, effectively
      "buttressing" the dimer interface. Our data also suggest that similar
      conformational changes may determine the specificity of ErbB receptor homo-
      versus heterodimerization.

PMID- 16107720
TI  - CD26 mediates dissociation of Tollip and IRAK-1 from caveolin-1 and induces
      upregulation of CD86 on antigen-presenting cells.
AB  - CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV enzyme
      activity in its extracellular region. We have previously reported that the
      addition of recombinant soluble CD26 resulted in enhanced proliferation of human
      T lymphocytes induced by the recall antigen tetanus toxoid (TT) via upregulation
      of CD86 on monocytes and that caveolin-1 was a binding protein of CD26, and the
      CD26-caveolin-1 interaction resulted in caveolin-1 phosphorylation (p-cav-1) as
      well as TT-mediated T-cell proliferation. However, the mechanism involved in this
      immune enhancement has not yet been elucidated. In the present work, we perform
      experiments to identify the molecular mechanisms by which p-cav-1 leads directly
      to the upregulation of CD86. Through proteomic analysis, we identify Tollip (Toll
      interacting protein) and IRAK-1 (interleukin-1 receptor-associated
      serine/threonine kinase 1) as caveolin-1-interacting proteins in monocytes. We
      also demonstrate that following stimulation by exogenous CD26, Tollip and IRAK-1
      dissociate from caveolin-1, and IRAK-1 is then phosphorylated in the cytosol,
      leading to the upregulation of CD86 via activation of NF-kappaB. Binding of CD26
      to caveolin-1 therefore regulates signaling pathways in antigen-presenting cells
      to induce antigen-specific T-cell proliferation.

PMID- 16107721
TI  - Manganese superoxide dismutase induces p53-dependent senescence in colorectal
      cancer cells.
AB  - The mitochondrial enzyme manganese superoxide dismutase (MnSOD) is known to
      suppress cell growth in different tumor cell lines. However, the molecular
      mechanism of this growth-retarding effect is not fully understood. Here we show
      that overexpression of MnSOD slows down growth of HCT116 human colorectal cancer
      cells by induction of cellular senescence. MnSOD overexpression causes up
      regulation of p53 and its transcriptional target, the cyclin-dependent kinase
      inhibitor p21. Adenovirus-mediated knockdown of p53 by RNA interference rescues
      MnSOD-overexpressing clones from growth retardation. Accordingly, the
      overexpression of MnSOD in HCTp53(-/-) cells does not lead to senescence, whereas
      in HCTp21(-/-) cells we found induction of senescence by forced expression of
      MnSOD. These results indicate a pivotal role of p53, but not p21, in the observed
      effects. Analysis of the mitochondrial membrane potential revealed reduced
      polarization in MnSOD-overexpressing cells. In addition, depolarization of the
      mitochondrial membrane by mitochondrial inhibitors such as rotenone or antimycin
      A led colorectal cancer cells into p53-dependent senescence. Our data indicate
      that uncoupling of the electrochemical gradient by increased MnSOD activity gives
      rise to p53 up-regulation and induction of senescence. This novel mitochondrially
      mediated mechanism of tumor suppression might enable strategies that allow
      reactivation of cellular aging in tumor cells.

PMID- 16107722
TI  - Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of
      the proximal tubule.
AB  - Aquaporin-11 (AQP11) has been identified with unusual pore-forming NPA
      (asparagine-proline-alanine) boxes, but its function is unknown. We investigated
      its potential contribution to the kidney. Immunohistochemistry revealed that
      AQP11 was localized intracellularly in the proximal tubule. When AQP11 was
      transfected in CHO-K1 cells, it was localized in intracellular organelles. AQP11
      null mice were generated; these mice exhibited vacuolization and cyst formation
      of the proximal tubule. AQP11-null mice were born normally but died before
      weaning due to advanced renal failure with polycystic kidneys, in which cysts
      occupied the whole cortex. Remarkably, cyst epithelia contained vacuoles. These
      vacuoles were present in the proximal tubules of newborn mice. In 3-week-old
      mice, these tubules contained multiple cysts. Primary cultured cells of the
      proximal tubule revealed an endosomal acidification defect in AQP11-null mice.
      These data demonstrate that AQP11 is essential for the proximal tubular function.
      AQP11-null mice are a novel model for polycystic kidney diseases and will provide
      a new mechanism for cystogenesis.

PMID- 16107723
TI  - Multiple fates of L1 retrotransposition intermediates in cultured human cells.
AB  - LINE-1 (L1) retrotransposons comprise approximately 17% of human DNA, yet little
      is known about L1 integration. Here, we characterized 100 retrotransposition
      events in HeLa cells and show that distinct DNA repair pathways can resolve L1
      cDNA retrotransposition intermediates. L1 cDNA resolution can lead to various
      forms of genetic instability including the generation of chimeric L1s,
      intrachromosomal deletions, intrachromosomal duplications, and intra-L1
      rearrangements as well as a possible interchromosomal translocation. The L1
      retrotransposition machinery also can mobilize U6 snRNA to new genomic locations,
      increasing the repertoire of noncoding RNAs that are mobilized by L1s. Finally,
      we have determined that the L1 reverse transcriptase can faithfully replicate its
      own transcript and has a base misincorporation error rate of approximately
      1/7,000 bases. These data indicate that L1 retrotransposition in transformed
      human cells can lead to a variety of genomic rearrangements and suggest that host
      processes act to restrict L1 integration in cultured human cells. Indeed, the
      initial steps in L1 retrotransposition may define a host/parasite battleground
      that serves to limit the number of active L1s in the genome.

PMID- 16107724
TI  - A dominant interfering Bub1 mutant is insufficient to induce or alter thymic
      tumorigenesis in vivo, even in a sensitized genetic background.
AB  - Aneuploidy is a common feature of human tumors, often correlating with poor
      prognosis. The mitotic spindle checkpoint is thought to play a major role in
      aneuploidy suppression. To investigate the role of the spindle checkpoint in
      tumor suppression in vivo, we developed transgenic mice in which thymocytes
      express a dominant interfering fragment of Bub1, a kinase regulator of the
      spindle checkpoint. We report that, despite high-level expression of dominant
      negative Bub1 (Bub1DN), a protein known to inhibit spindle checkpoint activity in
      cultured cells, thymocytes show no evidence of spindle checkpoint impairment.
      Transgenic animals also failed to show an increased predisposition to spontaneous
      tumors. Moreover, the Bub1DN transgene failed to alter the timing or
      characteristics of thymic lymphoma development in p53 heterozygous or homozygous
      null backgrounds, indicating that the lack of tumorigenesis is not due to
      suppression by p53-dependent checkpoints. These results indicate that
      overexpression of a Bub1 N-terminal fragment is insufficient to impair the
      spindle checkpoint in vivo or to drive tumorigenesis in the highly susceptible
      murine thymocyte system, either alone or in combination with G(1) checkpoint
      disruption.

PMID- 16107725
TI  - Mutational analysis of an RNA polymerase II elongation factor in Drosophila
      melanogaster.
AB  - The ELL family of proteins function in vitro as elongation factors for RNA
      polymerase II. Deletion studies have defined domains in mammalian ELL required
      for transcription elongation activity and RNA polymerase binding in vitro, for
      transformation of cultured cells when overexpressed, and for leukemogenesis and
      cell proliferation as part of a leukemic fusion protein. The goal of this study
      was to identify domains required for chromosome targeting and viability in the
      unique Drosophila ELL (dELL) protein. Here, we show that an N-terminal domain of
      dELL is necessary and sufficient for targeting to transcriptionally active puff
      sites in chromatin, supporting a role for this domain in recruiting dELL to
      elongating RNA polymerase II. We demonstrate that a central domain of dELL is
      required for rapid mobilization of ELL during the heat shock response, suggesting
      a regulatory function for this domain. Unexpectedly, transgenic dELL in which the
      N-terminal chromosome binding domain is deleted can complement the recessive
      lethality of mutations in ELL, suggesting that Drosophila ELL has an essential
      activity in development distinct from its role as an RNA polymerase II elongation
      factor.

PMID- 16107726
TI  - Complete loss of Ndel1 results in neuronal migration defects and early embryonic
      lethality.
AB  - Regulation of cytoplasmic dynein and microtubule dynamics is crucial for both
      mitotic cell division and neuronal migration. NDEL1 was identified as a protein
      interacting with LIS1, the protein product of a gene mutated in the
      lissencephaly. To elucidate NDEL1 function in vivo, we generated null and
      hypomorphic alleles of Ndel1 in mice by targeted gene disruption. Ndel1(-/-) mice
      were embryonic lethal at the peri-implantation stage like null mutants of Lis1
      and cytoplasmic dynein heavy chain. In addition, Ndel1(-/-) blastocysts failed to
      grow in culture and exhibited a cell proliferation defect in inner cell mass.
      Although Ndel1(+/-) mice displayed no obvious phenotypes, further reduction of
      NDEL1 by making null/hypomorph compound heterozygotes (Ndel1(cko/-)) resulted in
      histological defects consistent with mild neuronal migration defects. Double
      Lis1(cko/+)-Ndel1(+/-) mice or Lis1(+/-)-Ndel1(+/-) mice displayed more severe
      neuronal migration defects than Lis1(cko/+)-Ndel1(+/)(+) mice or Lis1(+/-)
      Ndel1(+/+) mice, respectively. We demonstrated distinct abnormalities in
      microtubule organization and similar defects in the distribution of beta-COP
      positive vesicles (to assess dynein function) between Ndel1 or Lis1-null MEFs, as
      well as similar neuronal migration defects in Ndel1- or Lis1-null granule cells.
      Rescue of these defects in mouse embryonic fibroblasts and granule cells by
      overexpressing LIS1, NDEL1, or NDE1 suggest that NDEL1, LIS1, and NDE1 act in a
      common pathway to regulate dynein but each has distinct roles in the regulation
      of microtubule organization and neuronal migration.

PMID- 16107727
TI  - Abnormalities caused by carbohydrate alterations in Ibeta6-N
      acetylglucosaminyltransferase-deficient mice.
AB  - Ibeta6-N-acetylglucosaminyltransferase (IGnT) catalyzes the branching of poly-N
      acetyllactosamine carbohydrate chains. In both humans and mice, three spliced
      forms of IGnT have been identified, and a common exon is present in all of them.
      We generated mice deficient in the common exon to understand the physiological
      function of poly-N-acetyllactosamine branching. IGnT activity was abolished in
      the stomach, kidney, bone marrow, and cerebellum of the deficient mice, while a
      low level of the activity persisted in the small intestine. Immunohistochemical
      analysis confirmed the loss of I antigen from the lung, stomach, and kidney. The
      deficient mice had reduced spontaneous locomotive activity. The number of
      peripheral blood lymphocytes was also reduced and renal function decreased in the
      deficient mice. Furthermore, in aged mice, vacuolization occurred in the kidney,
      and epidermoid cysts were frequently formed. However, cataracts did not develop
      earlier in the deficient mice. Decreased levels of lysosomal proteins, LAMP-2 and
      synaptotagmin VII, were found in the kidney of the deficient mice and correlated
      with renal abnormalities.

PMID- 16107728
TI  - Loss of SMEK, a novel, conserved protein, suppresses MEK1 null cell polarity,
      chemotaxis, and gene expression defects.
AB  - MEK/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase
      signaling is imperative for proper chemotaxis. Dictyostelium mek1(-) (MEK1 null)
      and erk1(-) cells exhibit severe defects in cell polarization and directional
      movement, but the molecules responsible for the mek1(-) and erk1(-) chemotaxis
      defects are unknown. Here, we describe a novel, evolutionarily conserved gene and
      protein (smkA and SMEK, respectively), whose loss partially suppresses the mek1(
      ) chemotaxis phenotypes. SMEK also has MEK1-independent functions: SMEK, but not
      MEK1, is required for proper cytokinesis during vegetative growth, timely exit
      from the mound stage during development, and myosin II assembly. SMEK localizes
      to the cell cortex through an EVH1 domain at its N terminus during vegetative
      growth. At the onset of development, SMEK translocates to the nucleus via a
      nuclear localization signal (NLS) at its C terminus. The importance of SMEK's
      nuclear localization is demonstrated by our findings that a mutant lacking the
      EVH1 domain complements SMEK deficiency, whereas a mutant lacking the NLS does
      not. Microarray analysis reveals that some genes are precociously expressed in
      mek1(-) and erk1(-) cells. The misexpression of some of these genes is suppressed
      in the smkA deletion. These data suggest that loss of MEK1/ERK1 signaling
      compromises gene expression and chemotaxis in a SMEK-dependent manner.

PMID- 16107729
TI  - Cationic sites on granzyme B contribute to cytotoxicity by promoting its uptake
      into target cells.
AB  - Granzyme B (GrB) is a key effector of cytotoxic lymphocyte-mediated cell death.
      It is delivered to target cells bound to the proteoglycan serglycin, but how it
      crosses the plasma membrane and accesses substrates in the cytoplasm is poorly
      understood. Here we identify two cationic sequences on GrB that facilitate its
      binding and uptake. Mutation of cationic sequence 1 (cs1) prevents accumulation
      of GrB in a distinctive intracellular compartment and reduces cytotoxicity 20
      fold. Mutation of cs2 reduces accumulation in this intracellular compartment and
      cytotoxicity two- to threefold. We also show that GrB-mediated cytotoxicity is
      abrogated by heparin and that target cells deficient in cell surface sulfate or
      glycosaminoglycans resist GrB. However, heparin does not completely prevent GrB
      internalization and chondroitin 4-sulfate does not inhibit cytotoxicity,
      suggesting that glycosaminoglycans are not essential GrB receptors. We propose
      that GrB enters cells by nonselective adsorptive pinocytosis, exchanging from
      chondroitin sulfate on serglycin to anionic components of the cell surface. In
      this electrostatic "exchange-adsorption" model, cs1 and cs2 participate in
      binding of GrB to the cell surface, thereby promoting its uptake and eventual
      release into the cytoplasm.

PMID- 16107730
TI  - c-Myc is required for the formation of intestinal crypts but dispensable for
      homeostasis of the adult intestinal epithelium.
AB  - In self-renewing tissues such as the skin epidermis and the bone marrow, Myc
      proteins control differentiation of stem cells and proliferation of progenitor
      cell types. In the epithelium of the small intestine, we show that c-Myc and N
      Myc are expressed in a differential manner. Whereas c-Myc is expressed in the
      proliferating transient-amplifying compartment of the crypts, N-Myc is restricted
      to the differentiated villus epithelium and a single cell located near the crypt
      base. c-Myc has been implicated as a critical target of the canonical Wnt
      pathway, which is essential for formation and maintenance of the intestinal
      mucosa. To genetically assess the role of c-Myc during development and
      homeostasis of the mammalian intestine we induced deletion of the c-myc(flox)
      allele in the villi and intestinal stem cell-bearing crypts of juvenile and adult
      mice, via tamoxifen-induced activation of the CreER(T2) recombinase, driven by
      the villin promoter. Absence of c-Myc activity in the juvenile mucosa at the
      onset of crypt morphogenesis leads to a failure to form normal numbers of crypts
      in the small intestine. However, all mice recover from this insult to form and
      maintain a normal epithelium in the absence of c-Myc activity and without
      apparent compensation by N-Myc or L-Myc. This study provides genetic and
      molecular evidence that proliferation and expansion of progenitors necessary to
      maintain the adult intestinal epithelium can unexpectedly occur in a Myc
      independent manner.

PMID- 16107731
TI  - A cross-kingdom internal ribosome entry site reveals a simplified mode of
      internal ribosome entry.
AB  - Rhopalosiphum padi virus (RhPV) is an insect virus of the Dicistroviridae family.
      Recently, the 579-nucleotide-long 5' untranslated region (UTR) of RhPV has been
      shown to contain an internal ribosome entry site (IRES) that functions
      efficiently in mammalian, plant, and insect in vitro translation systems. Here,
      the mechanism of action of the RhPV IRES has been characterized by reconstitution
      of mammalian 48S initiation complexes on the IRES from purified components
      combined with the toeprint assay. There is an absolute requirement for the
      initiation factors eIF2 and eIF3 and the scanning factor eIF1 to form 48S
      complexes on the IRES. In addition, eIF1A, eIF4F (or the C-terminal fragment of
      eIF4G), and eIF4A strongly stimulated the assembly of this complex, whereas eIF4B
      had no effect. Although the eIF4-dependent pathway is dominant in the RhPV IRES
      directed cell-free translation, omission of either eIF4G or eIF4A or both still
      allowed the assembly of 48S complexes from purified components with approximately
      23% of maximum efficiency. Deletions of up to 100 nucleotides throughout the 5'
      UTR sequence produced at most a marginal effect on the IRES activity, suggesting
      the absence of specific binding sites for initiation factors. Only deletion of
      the U-rich unstructured 380-nucleotide region proximal to the initiation codon
      resulted in a complete loss of the IRES activity. We suggest that the single
      stranded nature of the RhPV IRES accounts for its strong but less selective
      potential to bind key mRNA recruiting components of the translation initiation
      apparatus from diverse origins.

PMID- 16107732
TI  - The fission yeast Crb2/Chk1 pathway coordinates the DNA damage and spindle
      checkpoint in response to replication stress induced by topoisomerase I
      inhibitor.
AB  - Living organisms experience constant threats that challenge their genome
      stability. The DNA damage checkpoint pathway coordinates cell cycle progression
      with DNA repair when DNA is damaged, thus ensuring faithful transmission of the
      genome. The spindle assembly checkpoint inhibits chromosome segregation until all
      chromosomes are properly attached to the spindle, ensuring accurate partition of
      the genetic material. Both the DNA damage and spindle checkpoint pathways
      participate in genome integrity. However, no clear connection between these two
      pathways has been described. Here, we analyze mutants in the BRCT domains of
      fission yeast Crb2, which mediates Chk1 activation, and provide evidence for a
      novel function of the Chk1 pathway. When the Crb2 mutants experience damaged
      replication forks upon inhibition of the religation activity of topoisomerase I,
      the Chk1 DNA damage pathway induces sustained activation of the spindle
      checkpoint, which in turn delays metaphase-to-anaphase transition in a Mad2
      dependent fashion. This new pathway enhances cell survival and genome stability
      when cells undergo replicative stress in the absence of a proficient G(2)/M DNA
      damage checkpoint.

PMID- 16107733
TI  - Regulation of RelB expression during the initiation of dendritic cell
      differentiation.
AB  - The transcription factor RelB is required for proper development and function of
      dendritic cells (DCs), and its expression is upregulated early during
      differentiation from a variety of progenitors. We explored this mechanism of
      upregulation in the KG1 cell line model of a DC progenitor and in the
      differentiation-resistant KG1a subline. RelB expression is relatively higher in
      untreated KG1a cells but is upregulated only during differentiation of KG1 by an
      early enhancement of transcriptional elongation, followed by an increase in
      transcription initiation. Restoration of protein kinase CbetaII (PKCbetaII)
      expression in KG1a cells allows them to differentiate into DCs. We show that
      PKCbetaII also downregulated constitutive expression of NF-kappaB in KG1a
      transfected cells and restores the upregulation of RelB during differentiation by
      increased transcriptional initiation and elongation. The two mechanisms are
      independent and sensitive to PKC signaling levels. Conversely, RelB upregulation
      was inhibited in primary human monocytes where PKCbetaII expression was knocked
      down by small interfering RNA targeting. Altogether, the data show that RelB
      expression during DC differentiation is controlled by PKCbetaII-mediated
      regulation of transcriptional initiation and elongation.

PMID- 16107734
TI  - Survival signals generated by estrogen and phospholipase D in MCF-7 breast cancer
      cells are dependent on Myc.
AB  - Estrogens, which have been strongly implicated in the development of breast
      cancer, enhance proliferation of mammary epithelial cells and, importantly,
      estrogen receptor (ER)-positive breast cancer cells. In the absence of serum
      growth factors, the ER-positive MCF-7 breast cancer cell line undergoes
      apoptosis. Estrogens, most commonly 17-beta-estradiol (E2), can suppress
      apoptosis in MCF-7 cells deprived of serum. While E2 stimulated a short-term
      transient increase in Myc expression, E2 stimulated a sustained increase in Myc
      expression that was detectable at 48 h and pronounced at 5 days, the point where
      increased proliferation of MCF-7 cells in the absence of serum could be detected.
      The delayed increase in Myc expression was not dependent upon transcription of
      the Myc gene. Suppression of Myc expression reversed the survival effects of E2.
      The Myc-dependent survival signal generated by E2 was dependent upon basal levels
      of mTOR (mammalian target of rapamycin) and two upstream regulators of mTOR,
      phosphatidylinositol 3-kinase and phospholipase D (PLD). Stable elevated
      expression of PLD2 also increased Myc expression and provided a Myc-dependent
      survival signal in the absence of E2. These data provide evidence that E2
      promotes survival signals in breast cancer cells through an mTOR-dependent
      increase in Myc expression. The data also suggest that elevated PLD expression,
      which is common in breast cancer, confers E2 independence.

PMID- 16107739
TI  - Multiply charged ions in matrix-assisted laser desorption/ionization generated
      from electrosprayed sample layers.

PMID- 16107740
TI  - High-resolution time-of-flight spectra obtained using the MULTUM II multi-turn
      type time-of-flight mass spectrometer with an electron ionization ion source.
AB  - This paper describes experiments demonstrating the high mass-resolving power of
      the MULTUM II multi-turn type time-of-flight (ToF) mass spectrometer with a 1.308
      meter circuit controlled by four toroidal electric sector fields(1) and an
      electron ionization (EI) ion source. A mass resolution of 250,000 [full-width at
      half maximum: (FWHM)] was obtained for N(2)(+) after a flight time of 9.0 ms
      (flight cycles: 1,200, flight length: 1,500 M). A doublet of (12)C(5)H(5)(14)N
      and (13)C(12)C(5)H(6) (m/Deltam = 9,746; Deltam: mass difference of doublet, m:
      mass of lighter ion of doublet) was separated and a mass resolution of 91,000
      (FWHM) was obtained. A doublet of CDCl(2) and CH(2)Cl(2) (m/Deltam = 54,162) was
      also separated. A mass resolution of 115,000 (FWHM) was then achieved. When one
      peak of these doublets was used as a calibrant, the mass of the other peak was
      determined within a few ppm by mass difference. The ToF depending on the square
      of m/z was significantly larger than the systematic errors in the ToF, so that
      good mass accuracy was obtained by one-point mass determination.

PMID- 16107741
TI  - The generation of neutral derivatives of low-valence iron, RFe(I), by
      netralization-reionization mass spectrometry.
AB  - Neutralization-reionization mass spectrometry is applied for the generation of
      low-valence iron derivatives. Neutralization of Rfe(+) (R=H, F, Cl, Br, I, CN,
      OH, NH(2), acac, C(6)H(5)) ions resulted in the corresponding neutrals having
      lifetimes of at least 5 micros. Atom connectivities in RFe ions and neutrals were
      elucidated by a variety of tandem mass spectrometry techniques. The present study
      provides the first experimental evidence of the intrinsic stability of neutral
      IFe, NCFe, acacFe and C(6)H(5)Fe.

PMID- 16107742
TI  - Origin differentiation of heroin sample and its acetylating agent with (13)C
      isotope ratio mass spectrometry.
AB  - A novel method for deducing the origins of heroin and the reagent used for
      acetylation was established based on delta(13)C determinations of heroin and its
      hydrolysate, morphine, using gas chromatography (13)C isotope ratio mass
      spectrometry (GC-C-IRMS). The alkaline and acid hydrolysis conditions of heroin
      were optimized. Both yield and purity of morphine produced could meet the
      requirement for a GC-C-IRMS analysis. Using (2-diethylaminoethyl-2,2-
      diphenylvalerate) as internal standard the determinations of heroin and morphine
      contents were performed with a GC method in a linear range of 0.2 to 2.0 mg ml(1)
      that was required to gain the isotope ratio results. The hydrolysis and synthesis
      of heroin did not change the delta(13)C value of morphine. The precision for
      delta(13)C detection of both heroin and morphine was sufficient for origin
      differentiation of heroin samples. The information about the origins of
      acetylation reagents could be deduced from the difference of delta(13)C values
      between heroin and morphine. The results for origin differentiation of 10 heroin
      samples grouped into different regions and their acetylating agents were
      satisfactory.

PMID- 16107743
TI  - Soft deposition of organic macromolecules with fast atom bombardment mass
      spectrometry.
AB  - In order to investigate the requirements for soft deposition of intact positively
      charged organic macromolecules, an homogenous series of modal compounds such as
      polyphenylene dendronized perylenes (PDPs), C(80)H(52), C(200)H(132) and
      C(320)H(212) and a series of derivatives involving perylene derivative,
      C(98)H(104)N(8)O(4), terrylene derivative, C(78)H(82)N(6)O(4) and quaterrylene
      derivative, C(140)H(138)N(10)O(8), were used for soft-landing experiments on a
      metallic or matrix coated surface using fast atom bombardment mass spectrometry.
      Soft-landing can be achieved at impact energies below 180 eV with no production
      of fragments. The deposition rate shows strong energy dependence with similar
      behavior of the different organic compounds. A single isotope of the molecule was
      selected and soft-landed at increased resolution.

PMID- 16107744
TI  - Formation and reactions of clusters in the gas phase: small peptides and
      carboxylic acids.
AB  - The cluster formation of seventeen small dipeptides with different primary
      structures and vanillic acid was investigated by means of a neutral laser
      desorption and supersonic beam expansion followed by multi photon ionization time
      of flight mass spectrometry. The structures of these clusters have been
      characterized by mass spectrometric methods as well as by DFT calculations. It is
      shown that the structure of the cluster from a dipeptide and vanillic acid is
      described by a hydrogen bond between the phenolic group of the vanillic acid and
      the N-terminal amino function of the dipeptide. The intensity of the cluster ion
      and the main fragmentation product, the protonated peptide ion, can be linked to
      the proton affinity of the peptide. Furthermore the fragmentation reactions of
      the protonated peptide are accompanied by extensive hydrogen rearrangements
      yielding both a and y fragments. The intensities of these fragments follow the
      proton affinity of the dipeptide.

PMID- 16107745
TI  - Micro-synthesis and electron ionization mass spectral analysis of O-alkyl N,N
      dialkylphosphoramidocyanidates.
AB  - This communication describes microsynthesis and GC/MS analysis of O-alkyl N,N
      dialkylphosphoramidocyanidates (ADAPCs), which are analogues of chemical warfare
      agent, Tabun. The study was undertaken with a view to develop spectral data base
      of ADAPCs for verification purpose of Chemical Weapons Convention (CWC). Reported
      microsynthetic approach has advantages over traditional synthesis in terms of
      efficiency, synthetic waste, and exposure to toxic chemicals. GC/MS analysis of
      variety of these compounds (ADAPCs) was performed. Based on the obtained mass
      spectra of structurally diverse ADAPCs, the fragmentation routes are proposed,
      which explains most of the characteristic ions.

PMID- 16107746
TI  - Electrospray ionization-tandem mass spectrometry investigation of polymerization
      of tetrahydrofuran initiated by phosphorus oxychloride.
AB  - Phosphorus oxychloride was found to induce ring opening of tetrahydrofuran (THF)
      to synthesise THF oligomer incorporated phosphate. ESI multi-stage tandem mass
      spectrometry was used to study the products and confirm the structures.

PMID- 16107747
TI  - Analysis of benzylisoquinoline-type alkaloids by electrospray tandem mass
      spectrometry and atmospheric pressure photoionization.
AB  - Benzylisoquinoline alkaloids found in the Papaveraceae family play a major role
      in pharmaceutical biology. This is the first systematic study dealing with
      electrospray tandem mass spectrometry (ESI-MS/MS) of all benzylisoquinolines
      found as biogenetic precursors of morphinan alkaloids. Tandem mass spectral data
      are presented for norlaudanosoline, laudanosoline, 4'-O-methyl-norlaudanosoline,
      6-O-methyl-norlaudanosoline, norcoclaurine, coclaurine, N-methylcoclaurine, N
      methyl-3'-hydroxycoclaurine, N-methyl-3'-O-methylcoclaurine, norreticuline and
      reticuline. This study compares results obtained using an ion trap mass
      spectrometer with those obtained using a triple quadrupole one. The results
      highlight the differences of the tandem-in-time versus the tandem-in-space
      principle, often hampering the development of ESI-MS/MS libraries. Additionally,
      the use of the atmospheric pressure photoionisation technique for the analysis of
      such substances is discussed.

PMID- 16107748
TI  - Identification of phosphorylcholine substituted peptides by their characteristic
      mass spectrometric fragmentation.
AB  - Phosphorylcholine (PC) substituted biomolecules are wide-spread, highly relevant
      antigens of parasites, since this small hapten has been found to be a potent
      immunomodulatory component which allows the establishment of long lasting
      infections of the host. Structural data, especially of protein bound PC
      substituents, are still rare due to the observation that mass spectrometric
      analyses are mostly hampered by this zwitterionic substituent resulting in low
      sensitivities and unusual but characteristic fragmentation patterns. Here we
      investigated the fragmentation behaviour of synthetic PC-substituted peptides by
      matrix-assisted laser desorption/ionization mass spectrometry and electrospray
      ionization ion trap mass spectrometry. We could show that the predominant neutral
      loss of a trimethylamine unit (Hoffmann elimination) leads to cyclic phosphate
      derivatives which prevent further fragmentation of the peptide backbone by
      stabilizing the positive charge at this particular side chain. Knowledge of this
      PC-specific fragmentation might help to identify PC-substituted biomolecules and
      facilitate their structural analysis.

PMID- 16107749
TI  - Tandem mass spectrometric approach for determining the structure of molecular
      species of ceramide in the marine sponge Haliclona cribricutis.
AB  - Ceramides are important intracellular second messengers that play a role in the
      regulation of cell growth, differentiation and programmed cell death. Analysis of
      these second messengers requires sensitive and specific analytical method to
      detect individual ceramide species and to differentiate between them. Eight
      molecular species of ceramide were identified from the marine sponge Haliclona
      cribricutis using electrospray ionization tandem mass spectrometry (ESI-MS/MS).
      From this marine sponge N-hencicosanoyl (N21:0) to N-hexasanoyl (N26:0)
      Octadecasphing-4 (E)-enine have been reported for the first time. The ESI-MS
      spectra gave several strong protonated molecular ion [M+H](+) with the
      corresponding bis (2-ethyl hexyl) phthalate adduct [M+H+DHEP](+). The collision
      induced dissociation (CID) on ceramides at m/z 622.7337, 636.7645, 650.7789,
      664.7925 and 678.8130 conducted at low-collision energy produced well
      characteristic product ions at m/z 252.31, 264.32, 278.33, 282.33 and 296 .35 for
      d18:1 sphingosine regardless of the length of the fatty chain. The MS/MS of the
      Phthalate adduct [M+H+DHEP](+) at m/z 1013.1820, 1027.1971, 1041.2176, 1055.2394
      and 1069.2573 also yielded characterizing product ions for sphingosine and
      confirmed the molecular ion at m/z 391 for bis (2-ethyl hexyl) phthalate. The
      major ions in the [M+H](+) and [M+H+DHEP](+) were due to neutral loss of [M+H
      H(2)O](+) and [M+H(H(2)O)(2)](+).

PMID- 16107750
TI  - Search for melanoma markers in plasma and serum samples.
AB  - Fourteen blood samples from patients with melanoma and eleven blood samples from
      healthy subjects were analyzed by matrix-assisted laser desorption/ionization
      (MALDI) mass spectrometry. The study was focussed on species of low molecular
      weight, in the range 800-5000 Da, present in plasma and sera. While for healthy
      subjects plasma samples lead to the production of a higher number of ionic
      species, for melanoma patients a high number of diagnostic ions, present with
      high frequency and with quite high relative abundance, are present in particular
      in serum samples and to a lesser extent also in plasma. Since plasma samples are
      obtained more easily in comparison to sera, it is possible to suggest that also
      plasma can be used for these studies.

PMID- 16107751
TI  - Studies on the application of immobilization technique for the production of
      cyclosporin A by a local strain of Aspergillus terreus.
AB  - The formation of cyclosporin A (Cy A) by immobilized spores and mycelia of
      Aspergillus terreus was investigated. Different carriers were tested as
      immobilizing carriers, whereby Ca-alginate was selected for further
      experimentation. The role of alginate concentration, biomass weight, pH value of
      the cultivation medium, repeated utilization of the immobilized fungus as well as
      the supplementation of different amino acid precursors were studied. Best Cy A
      outputs were attained with Ca-alginate 3% (w/v), mycelial weight 15% (w/v), pH
      4.5 and four repeated cycles. Similarly, the Cy A productivity was markedly
      accelerated in the presence of L-valine and L-valine and L-leucine mixture.

PMID- 16107752
TI  - Degradation of polyesters by a novel marine Nocardiopsis aegyptia sp. nov.:
      application of Plackett-Burman experimental design for the improvement of PHB
      depolymerase activity.
AB  - This is the first report on the degradation of poly(3-hydroxybutyrate) (PHB), and
      its copolymers poly(3-hydroxyvalerate) P(3HB-co-10-20% HV) by Nocardiopsis
      aegyptia, a new species isolated from marine seashore sediments. The strain
      excreted an extracellular PHB depolymerase and grew efficiently on PHB or its
      copolymers as the sole carbon sources. The degradation activity was detectable by
      the formation of a transparent clearing zone around the colony on an agar Petri
      plate after 25 days, or a clearing depth under the colony in test tubes within 3
      weeks. The previous techniques proved that the bacterium was able to assimilate
      the monomeric components of the shorter alkyl groups of the polymers.
      Nocardiopsis aegyptia hydrolyzed copolymers 10-20% PHBV more rapidly than the
      homopolymer PHB. The bacterial degradation of the naturally occurring sheets of
      poly(3-hydroxybutyrate), and its copolymer poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) was observed by scanning electron microscopy (SEM). The samples
      were degraded at the surface and proceeded to the inner part of the materials.
      Clear morphological alterations of the polymers were noticed, indicating the
      degradative capability of the bacterium. Plackett-Burman statistical experimental
      design has been employed to optimize culture conditions for maximal enzyme
      activity. The main factors that had significant positive effects on PHB
      depolymerase activity of Nocardiopsis aegyptia were sodium gluconate, volume of
      medium/flask and age of inoculum. On the other hand, MgSO4.7H2O, KH2PO4, K2HPO4
      and NH4NO3 exhibited negative effects. Under optimized culture conditions, the
      highest activity (0.664 U/mg protein) was achieved in a medium predicted to be
      near optimum containing (in g/L): PHB, 0.5; C6H11O7Na, 7.5; MgSO4.7H2O, 0.35;
      K2HPO4, 0.35; NH4NO3, 0.5; KH2PO4, 0.35; malt extract, 0.5 and prepared with 50%
      seawater. The medium was inoculated with 1% (v/v) spore suspension of 7 days old
      culture. Complete clarity of the medium was achieved after 3 days at 30 degrees
      C.

PMID- 16107753
TI  - Bacteriophage Esc-A is an efficient therapy for Escherichia coli 3-1 caused
      diarrhea in chickens.
AB  - The bacteriophage Esc-A was isolated from sewage by using the intestinal
      pathogenic Escherichia coli 3-1 as the host. Toxicity in chickens showed its
      safety as a bio-product. Phage therapy against diarrhea in chickens indicated
      that Esc-A could decrease the death rate more efficiently compared with
      antibiotic treatments.

PMID- 16107754
TI  - Maltose adaptive mutant of heterotrophic marine bacterium, Alteromonas espejiana
      Bal-31: changes in the growth and the induction of extracellular alpha-amylase.
AB  - Growth of the heterotrophic marine bacterium, Alteromonas espejiana Bal-31 was
      inhibited in the presence of sucrose, maltose and even glucose, but not with
      starch. Extracellular alpha-amylase was induced with a lag phase of 2 h in the
      presence of starch. In contrast, cell growth of the S2a mutant was not affected
      by the addition of maltose, and starch was ineffective in the induction of
      extracellular alpha-amylase in this mutant. Activity of extracellular alpha
      amylase was induced from the S2a mutant with a 4-h lag phase in the presence of
      maltose, and the high level of enzyme activity was maintained for at least 24 h.
      Activity of alpha-amylase induced by both wild type starch and S2a mutant maltose
      cultures were mainly observed in extracellular locations. This activity could be
      stopped by tetracycline treatment, indicating that enzyme induction was dependant
      on gene expression and not on enzyme protein secretory mechanisms. Our results
      showed that the mutation in S2a changed the growth and the modulation of the
      specific alpha-amylase in response to carbon nutrients.

PMID- 16107755
TI  - Purification and characterization of a thermostable glucoamylase from Chaetomium
      thermophilum.
AB  - Thermostable amylolytic enzymes are currently being investigated to improve
      industrial processes of starch degradation. A thermostable extracellular
      glucoamylase (exo-1, 4-alpha-D-glucanohydrolase, E.C.3.2.1.3) from the culture
      supernatant of a thermophilic fungus Chaetomium thermophilum was purified to
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) homogeneity
      by using ammonium sulfate fraction, DEAE-Sepharose Fast Flow chromatography, and
      Phenyl-Sepharose Fast Flow chromatography. SDS-PAGE of the purified enzyme showed
      a single protein band of molecular weight 64 kDa. The glucoamylase exhibited
      optimum catalytic activity at pH 4.0 and 65 degrees C. It was thermostable at 50
      degrees C and 60 degrees C, and retained 50% activity after 60 min at 65 degrees
      C. The half-life of the enzyme at 70 degrees C was 20 min. N-terminal amino acid
      sequencing (15 residues) was AVDSYIERETPIAWN. Different metal ions showed
      different effects on the glucoamylase activity. Ca2+, Mg2+, Na+, and K+ enhanced
      the enzyme activity, whereas Fe2+, Ag+, and Hg2+ cause obvious inhibition. These
      properties make it applicable to other biotechnological purposes.

PMID- 16107756
TI  - Geobacillus thermoleovorans subsp. stromboliensis subsp. nov., isolated from the
      geothermal volcanic environment.
AB  - A novel thermophilic, aerobic, endospore-forming bacterium, designated strain
      PizzoT, was isolated from geothermal volcanic environment. Samples were collected
      from the Pizzo sopra la Fossa site at Stromboli Island (Eolian Islands, south of
      Italy) at the high altitude of 918 m. Cells of strain PizzoT were rod-shaped and
      stained Gram-positive. Growth was observed between 50 and 75 degrees C (optimum
      70 degrees C) and at pH 5.0-8.0 (optimum pH 7.0). NaCl (0.4%, w/v) supported
      growth and among the hydrocarbons tested none induced growth. The G+C content of
      the DNA was 54.1 mol% and the sequence analysis of the 16S rRNA gene showed that
      the new isolate was phylogenetically closely related to the members of the
      Bacillus rRNA Group 5. DNA-DNA hybridization studies revealed a borderline
      similarity between the new isolate and Geobacillus thermoleovorans DSM 5366T
      (69.8%) and Geobacillus kaustophilus DSM 7263T (63.4%). On the basis of
      phylogenetic analysis and physiological traits of the isolate, it should be
      described as a new member of the Geobacillus thermoleovorans species and it is
      proposed that strain PizzoT can be classified as Geobacillus thermoleovorans
      subsp. stromboliensis, subsp. nov. (ATCC BAA-979T; DSM 15393T).

PMID- 16107757
TI  - Identification of genes required for decolorization of crystal violet in
      Citrobacter sp. MY-5.

PMID- 16107758
TI  - Characterization of bacterial communities of a constructed wetland in cold
      conditions.

PMID- 16107759
TI  - Regulation of mast cell development.
AB  - Human mast cells originated from multipotential hematopoietic progenitors in bone
      marrow (BM). A large proportion of these progenitors were CD34+CD38-c-kit+ cells
      and CD34+CD38+c-kit+ cells. Cloning of stem cell factor (SCF) contributed to the
      development of culture systems of human mast cells from different sources
      including BM mononuclear cells, CD34+ cord blood (CB) cells, and fetal liver
      cells. SCF could support mast cell development from CD34+ CB cells in the serum
      deprived culture system. The cumulative mast cell number reached 10(10)-fold the
      input quantity at 50 weeks of SCF-containing serumdeprived culture. CB-derived
      mast cells expressed tryptase, chymase, and histamine similar to mast cells
      residing in tissues. The surface expression of FcepsilonRI, however, was very low
      on fetal liver- or CB-derived mast cells. Factors that had effects on SCF
      dependent human mast cell development were divided into four types: (1) factors
      that stimulated both proliferation and maturation: SCF; (2) factors that
      stimulated only proliferation: thrombopoietin, interleukin (IL)-9; (3) factors
      that inhibited proliferation, but stimulated maturation: IL-4, IL-6, and (4)
      factors that inhibited proliferation and maturation: retinoids.

PMID- 16107760
TI  - Regulation of mast cell activation through FcepsilonRI.
AB  - The cross-linking of FcepsilonRI on mast cells by IgE and antigen (Ag) initiates
      activation cascades that lead to allergic responses. FcepsilonRI is composed of
      an alpha and a Beta monomer, and a gamma homodimer, and the Beta and gamma chains
      possess immunoreceptor tyrosine-based activation motifs (ITAMs). Through the
      phosphorylation of ITAMs, activation signals are transmitted intracellularly.
      Mast cells are also activated through FcgammaR-FcRgamma by an immune complex,
      which often results in hypersensitivity. We defined FcRgamma-signal-dependent and
      -independent mast cell responses by analyzing FcRgamma-/- mice reconstituted with
      mutant FcRepsilon-ITAM. Most of the FcepsilonRI-mediated activations by IgE(+Ag),
      such as induction of degranulation, arachidonic acid metabolism, cytokine
      production and systemic anaphylaxis, are dependent on signaling through FcRgamma
      ITAM. On the other hand, IgE without Ag induces the upregulation of surface
      FcepsilonRI expression and mast cell survival. The former is independent of and
      the latter is dependent on FcRgamma-ITAM. As a molecular mechanism for the
      generation of diverse responses through FcepsilonRI, we found that the quantity
      and the duration of the FcRgamma signal determine the degranulation and the
      survival of mast cells, respectively. Furthermore, such a sustained FcRgamma
      signal-induced survival is mediated by autocrine cytokine production. In this
      review, the in vivo function of FcRgamma and the signal regulation for the
      distinct responses of mast cells through FcepsilonRI are discussed.

PMID- 16107761
TI  - Role of oxidants in mast cell activation.
AB  - Reactive oxygen species (ROS), such as superoxide, hydrogen peroxide (H2O2), and
      hydroxyl radical, have for a long time been considered as accidental by-products
      of respiratory energy production in mitochondria and as being useless and rather
      deleterious to biological systems. Contrary to such a classical view,
      accumulating evidence indicates that upon stimulation of divergent receptor
      systems, ROS are intentionally produced and even required for appropriate signal
      transduction and biological responses. Work by our group and that of others have
      shown that stimulation of mast cells through the high-affinity IgE receptor
      (FcepsilonRI) induces the production of ROS such as superoxide and H2O2 possibly
      by the phagocyte NADPH oxidase homologue and that these endogenously produced
      oxidants have important functions in regulation of various mast cell responses,
      including degranulation, leukotriene secretion, and cytokine production.
      Subsequent studies have defined particular biochemical pathways that can be
      targeted by ROS and/or cellular redox balance. More recent research reveals that
      ROS may also play an important role in mast cell activation by divergent allergy
      relevant environmental substances, for instance heavy metals and polycyclic
      aromatic hydrocarbons. This review summarizes current knowledge on the role of
      endogenous oxidants in mast cell activation.

PMID- 16107762
TI  - Roles of adaptor molecules in mast cell activation.
AB  - The release of pro-inflammatory mediators from mast cells generally occurs
      following antigen-dependent aggregation of the high-affinity receptors for IgE
      (FcepsilonRI) expressed on the cell surface. Under the appropriate conditions,
      however, other receptors including the high-affinity receptor for IgG
      (FcgammaRI), Kit, the C3a complement component receptor, and adenosine receptors,
      can also induce or potentiate mast cell activation. In contrast, receptors such
      as the FcgammaRIIb low-affinity IgG receptor, and gp49b, when co-ligated with
      FcepsilonRI, down-regulate mast cell activation. The driving force by which the
      FcepsilonRI, the FcgammaRI, Kit, and potentially other receptors, lead to mast
      cell degranulation, arachidonic acid metabolism and cytokine gene expression, is
      a series of tyrosine kinase-mediated protein phosphorylation events which result
      in recruitment and subsequent activation of signaling enzymes. Similar processes
      are required by gp49b and FcgammaRIIb for the down-regulation of mast cell
      activation. The cellular localization and sequence of these events, the
      subsequent amplification and diversification of the signaling cascade, and
      potentially, the termination of these events, are regulated by an important group
      of signaling proteins termed adaptor molecules. In this chapter, we discuss the
      structure and properties of these molecules and how these proteins regulate the
      cellular processes associated with receptor-mediated mast cell activation.

PMID- 16107763
TI  - Eicosanoid mediators of mast cells: receptors, regulation of synthesis, and
      pathobiologic implications.
AB  - When activated by diverse stimuli, mast cells mobilize arachidonic acid through
      cytosolic phospholipase A2, and rapidly generate both prostaglandin D2 and
      leukotriene C4, the parent molecule of the cysteinyl LTs. While initially
      recognized for their bronchoconstricting and vasoactive properties, these two
      eicosanoids are now known to serve diverse and pivotal functions in effector cell
      trafficking, antigen presentation, immune cell activation, matrix deposition, and
      fibrosis. This chapter reviews the biological functions for each eicosanoid and
      their respective receptor classes, discusses the mechanisms by which the
      generation of eicosanoids by mast cells is regulated, and considers the potential
      pathobiologic and therapeutic ramifications in host defense, inflammation, and
      allergic diseases.

PMID- 16107764
TI  - Role of mast cell proteases in tissue remodeling.
AB  - Mast cells specifically localize within the bronchial smooth muscle bundles in
      patients with asthma but not in normal individuals. Tryptase and other proteases
      such as chymase are abundant in mast cell granules and have recently been
      reported to be involved in the proliferation of airway smooth muscle cells. In
      this chapter, therefore, the role of proteases other than fibrolytic activity is
      reviewed.

PMID- 16107765
TI  - Mast cell mediators in airway remodeling.
AB  - Increasing evidence indicates that airway remodeling plays an important part in
      asthma pathogenesis. However, mechanisms underlying airway remodeling are not yet
      fully elucidated. Plasminogen activator inhibitor (PAI)-1 is the main inhibitor
      of the fibrinolytic system and is known to play an essential role in tissue
      remodeling. Recent evidence indicates that chronic asthma may lead to tissue
      remodeling such as subepithelial fibrosis and extracellular matrix (ECM)
      deposition in the airways. Recently, the mast cell (MC), which plays a major role
      in asthma, is found as a novel source of PAI-1 and a large number of MCs
      expressing PAI-1 are infiltrated in the airways of patients with severe asthma.
      Furthermore, PAI-1-deficient mice show reduced ECM deposition in the airways of a
      murine model of chronic asthma. In a human study, the 4G allele frequency was
      significantly higher in the asthmatic patients than in the control group. In view
      of the findings that the 4G allele is associated with elevated plasma PAI-1
      level, elevated PAI-1 level in the lung may contribute to the development of
      airway remodeling. In summary, MCs may play an important role in the pathogenesis
      of asthma in part by producing PAI-1. Further studies evaluating the mechanisms
      of PAI-1 action may provide a new paradigm in airway remodeling and lead to the
      development of a novel therapeutic target.

PMID- 16107766
TI  - Mast cell-derived cytokine expression induced via Fc receptors and Toll-like
      receptors.
AB  - It is now well established that human mast cells (MCs) are a source of several
      multifunctional cytokines. Preformed immunoreactive tumor necrosis factor-alpha
      (TNF-alpha) has been observed within human skin, and pulmonary MC granules are
      released after IgE-dependent activation. Recent studies in animal models indicate
      that mouse MCs may play a protective role in host defense against bacteria
      through production of TNF-alpha, mainly as a result of Toll-like receptor 4
      (TLR4)- or CD48-mediated activation. Moreover, several recent observations in
      animal models have indicated that MCs may also play a pivotal role in
      coordinating the early phases of autoimmune diseases through production of TNF
      alpha, particularly as a result of FcgammaRIII-mediated activation by
      autoantibodies. The questions now concern how MCs modulate immune responses and
      what cytokines MCs release through activation of each receptor. Since we recently
      identified functional TLR4 and FcgammaRI on human MCs, in this study we used high
      density oligonucleotide probe arrays (GeneChip) to compare each of the receptor
      mediated gene expression profiles with the FcepsilonRI-mediated gene expression
      profile. The results indicated that human MCs might modulate the immune system in
      a receptor-specific manner by releasing cytokines in quantitatively and
      qualitatively different ways.

PMID- 16107767
TI  - Mast cells in allergic airway disease and chronic rhinosinusitis.
AB  - Conventional knowledge tells us that mast cells are only important in the acute
      IgE-mediated reactions as seen in anaphylaxis, asthma and rhinitis. Yet, in
      recent years, much evidence has accumulated on the versatile role of mast cells
      in allergic inflammation. Here, we describe the novel and potential roles of mast
      cells in the late phase allergic reaction as well as in chronic allergic
      inflammation. Mast cells in patients with allergic rhinitis and asthma produce
      Th2 type cytokines, induce IgE synthesis in B cells and can autoactivate itself
      via the mast cell-IgE-FcepsilonRI cascade. In addition, mast cells upregulate the
      production of a variety of cytokines/chemokines in epithelial cells and
      fibroblasts and induce the recruitment of basophils, T cells and eosinophils into
      sites of allergic inflammation as well as their own intraepithelial accumulation.
      Furthermore, mast cells express MMPs and interact with extracellular matrix
      proteins and ASM and may play a role in nasal and bronchial hyperresponsiveness
      as well as tissue remodelling. In chronic rhinosinusitis with nasal polyps, the
      potential role of mast cells not only in orchestrating eosinophilic inflammation
      but also in the genesis and perpetuation of nasal polyp formation via FcepsilonRI
      and TLR mediated activation is also of growing interest.

PMID- 16107768
TI  - Chemokine receptor expression by mast cells.
AB  - There is a growing interest in the role of chemokines and their receptors in the
      determination of mast cell tissue localization and how chemokines regulate mast
      cell function. At least nine chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4,
      CX3CR1, CCR1, CCR3, CCR4 and CCR5) have been described to be expressed by human
      mast cells of different origins. Seven chemokines (CXCL1, CXCL5, CXCL8, CXCL14,
      CX3CL1, CCL5 and CCL11) have been shown to act on some of these receptors and to
      induce mast cell migration. Mast cells have a unique expression pattern of CCR3,
      CXCR1 and CXCR2. These receptors are mainly expressed intracellularly on
      cytoplasmic membranes. Upon an allergic activation, CCR3 expression is increased
      on the cell surface and the cell becomes vulnerable for CCL11 treatment.
      Chemokines do not induce mast cell degranulation but CXCL14 causes secretion of
      de novo synthesized CXCL8. Because of the expression of CCR3, CCR5 and CXCR4 on
      mast cell progenitors, these cells are susceptible to HIV infection and mast
      cells might therefore be a persistent HIV reservoir in AIDS. In this review, we
      summarize the knowledge about chemokine receptor expression and function on mast
      cells.

PMID- 16107769
TI  - Mast cell beta2-adrenoceptors.
AB  - The human lung mast cell is a crucial effector cell in the mediation of asthma.
      Activation of mast cells by allergens, and other insults, leads to the
      elaboration of a wide variety of autacoids that cause bronchoconstriction and
      promote inflammation. Of the drugs that are used to treat asthma, only
      bronchodilator beta2-adrenoceptor agonists are effective at inhibiting the
      elaboration of mediators from mast cells. Both short- and long-acting beta2
      adrenoceptor agonists are effective inhibitors of mast cells although there are
      differences in the degree of inhibitory activity attained with a given agonist.
      Human lung mast cells express a homogeneous population of beta2-adrenoceptors.
      However, the density of beta2-adrenoceptors differs from preparation to
      preparation and this may influence the extent to which agonists stabilise mast
      cell activity. Tolerance to the mast cell-stabilising activity of beta2
      adrenoceptor agonists can be readily demonstrated. As a generalisation, agonists
      that are more effective inhibitors of mediator release also induce greater levels
      of tolerance although weaker agonists induce greater levels of tolerance than
      might be expected. However, the extent of tolerance does not correlate with the
      degree of beta2-adrenoceptor loss. The inhibitory activity of agonists and the
      extent of tolerance observed may be influenced by genetic polymorphisms in the
      gene for the beta2-adrenoceptor.

PMID- 16107770
TI  - Potential role of stem cell factor in the asthma control by glucocorticoids.
AB  - Asthma is an allergic disease characterized by inflammation that includes an
      increase in the number and activation of mast cells in the airways.
      Glucocorticoids, on the other hand, diminish inflammation as well as the number
      of mast cells in this disease. Stem cell factor (SCF) is a major growth factor
      for human mast cells, inducing chemotaxis as well as survival of the mast cells.
      SCF induces proliferation and differentiation of immature mast cells from CD34+
      progenitors. It also potentiates the IgE-dependent activation of mast cells.
      Furthermore, SCF expression is reduced in the airways of asthmatic patients
      treated with glucocorticoids. Thus, SCF could be involved in mast cell-associated
      diseases such as asthma. We here review the main effects of glucocorticoids in
      asthma and on mast cells, with a special interest on SCF, as a potential
      therapeutic target in asthma.

PMID- 16107771
TI  - Mast cell ion channels.
AB  - IgE-dependent activation of human mast cells is a central feature of allergy.
      However, alternative non-IgE-mediated signals derived from the complex
      inflammatory milieu are also important in driving chronic mast cell activation in
      many tissues. Irrespective of the point from where pathological secretion is
      sustained, all mechanisms will change the activity of the final 'effector' ion
      channels involved in normal stimulus-secretion coupling. IgE-dependent activation
      of human mast cells is characterised by an influx of extracellular Ca2+, which is
      essential for subsequent release of both preformed (granule-derived) mediators
      and newly generated autacoids and cytokines. In addition, flow of ions such as K+
      and Cl- are likely to play an important role in mast cell activation through
      their effect on cell membrane potential and thus Ca2+ influx. Emerging evidence
      suggests that mast cells express a number of channels carrying K+, Cl- and Ca2+.
      With current techniques it will be possible to identify the molecular origin of
      these channels and define precisely their role in mast cell function. Mast cell
      ion channels offer a novel target for the attenuation of allergic disease.

PMID- 16107772
TI  - Using mast cell knock-in mice to analyze the roles of mast cells in allergic
      responses in vivo.
AB  - It is well established that mast cells are important effector cells mediating the
      acute phase of IgE-associated allergic disorders, but their roles in late phase
      reactions and chronic allergic inflammation are not well defined. Here we
      describe an experimental approach for analyzing mast cell functions in vivo by
      comparing the biological responses in wild-type mice, genetically mast cell
      deficient mice, and 'mast cell knock-in mice' (mast cell-deficient mice
      selectively repaired of their mast cell deficiency). Studies using 'mast cell
      knock-in mice' have indicated that mast cells can contribute importantly to IgE
      associated late phase reactions and to chronic allergic inflammation. Moreover,
      'mast cell knock-in mice' containing adoptive-transferred mast cell populations
      with defined alterations in the expression of specific mast cell products can be
      used to characterize the mechanisms by which mast cells contribute to the
      expression of the response of interest.

PMID- 16107773
TI  - Mast cell-specific genes--new drug targets/pathogenesis.
AB  - It has become possible to see all the expressed genes present in a cell
      (transcriptome) at once using microarray. We have applied microarray technology
      in various studies involving allergic diseases. Although we and others have
      discovered various novel molecules crucially involved in the pathogenesis of the
      disease, transcriptome assay is now expected as a tool for understanding the
      whole molecule balancing, i.e., system biology. Here I introduce examples of our
      trials for understanding the whole functional roles of mast cells as has been
      published in the web database for transcriptomes expressed by several mast cell
      types and various cell types. In the near future, we will be able to construct
      human mast cell models in silico (in a computer) by analyzing integrative
      information regarding the genome, transcriptome and proteome of mast cells, and
      will be able to test our hypotheses without having to perform in vitro tests.

PMID- 16107774
TI  - Comparison of anterior instrumentation systems and the results of minimum 5 years
      follow-up in the treatment of tuberculosis spondylitis.
AB  - Anterior debridement, strut grafting and instrumentation have an increasing
      popularity in the treatment of tuberculosis of spine. Anterior fixation can be
      done either by a plate or a rod system. This study reports on the surgical
      results of 59 patients with Pott's disease that had anterior radical debridement
      and anterior fusion and anterior instrumentation with 5 years follow-up. Average
      age at the time of operation was 46.3+/-13.5 years. Average follow-up was 84.6+/
      11.3 months. Local kyphosis was measured as the angle between the upper and lower
      end plates of the collapsed vertebrae preoperatively, postoperatively and at the
      last follow-up visit. Vertebral collapse, destruction, cold abscess, and canal
      compromise were assessed in MR images. The indication for surgery was either one
      of the deformity, instability or neurological compromise. Surgical treatment
      included anterior radical debridement followed by grafting with tricortical auto
      graft and anterior instrumentation at levels just above and below the diseased
      segment(s) with either plate (Sofamor-Danek, Z plate, Group A) or rod (Sofamor
      Danek, CDH, Group B) systems. There were 23 patients in group A and 36 patients
      in group B. All patients had similar anti tuberculosis chemotherapy. Patients had
      similar rehabilitation program after the surgery. The deformity in the sagittal
      and the coronal plane was measured and presence of significant consolidation,
      along with the absence of implant failure or correction loss was considered as
      signs of fusion. The two groups were similar according to age (46.9+/-14.2 vs.
      45.8+/-13.1), gender, average number of involved levels (1.8+/-0.5 vs. 1.6+/
      0.5), location of involved levels, severity of deformity (21.5 degrees+/-9.9
      masculine vs. 24.8 degrees+/-11.9 masculine) and type of autografts (p>0.05 for
      all parameters). 39.1 % of patients in group A and 41.6 % of patients in group B
      had neurological compromise with improvement in majority at the end of follow-up.
      Deformities were corrected to 5.2 degrees+/-5.7 masculine in group A and 6.1
      degrees+/-6.8 masculine in group B with no significant difference. At the time of
      latest follow-up there were 1.7 degrees+/-2.0 masculine correction loss in group
      A and 1.4 degrees+/-1.9 masculine in group B with no significant difference in
      between two groups (p>0.05). Overall, it was observed that, the addition of
      anterior instrumentation increased the rate of correction of the kyphotic
      deformity (78.5+/-20.5%), and was effective in maintaining it with an average
      loss of 1.5 degrees+/-1.9 degrees. Of the 24 (44.1%) patients with neurological
      symptoms, 20 (83.3%) had full and 4 (16.7%) partial recoveries. There was no
      apparent pseudoarthrosis and implant failure in both groups and all patients
      demonstrated clinical improvement in tuberculosis infection without recurrences
      and reactivation. Four major complications occurred in the group A (major vessel
      complication: 3.4%, secondary non-specific infection: 3.4%). Disease reactivation
      was not seen with the employment of an aggressive chemotherapy regimen. It was
      concluded that anterior instrumentation is a safe and effective method in the
      treatment of tuberculosis spondylitis. There were no significant differences
      between the two instrumentation systems in terms of sagittal alignment
      reconstruction and fusion rate. In rod-screw systems, the disadvantages of
      scoliotic deformity correction through frontal plan in plate performing did not
      occur and it is though to have the advantage of long instrumentation in multiple
      level deformities.

PMID- 16107775
TI  - MDR1, MRP1 and MRP2 genotypes and in vitro chemosensitivity in Japanese patients
      with colorectal adenocarcinomas.
AB  - In our previous paper, the chemosensitivity of human colorectal adenocarcinoma
      was evaluated against 12 anticancer drugs including 5-fluorouracil (5-FU), 7
      ethyl-10-hydroxycamptothecin (SN-38), mitomycin C (MMC) and cisplatin (CDDP), and
      it was found that the anticancer drugs were effective against those with a
      relatively high growth rate. MMC was effective for those with a relatively high
      mRNA expression of the multidrug resistance-associated protein 2 (MRP2), whereas
      no correlation was found for the multidrug resistant transporter MDR1 and MRP1.
      In this study, 3 genotypes of MDR1, 4 genotypes of MRP1, and 6 genotypes of MRP2
      were additionally evaluated, and it was suggested that MDR1 C3435T and MRP2
      G1249A were related with the susceptibility to colorectal adenocarcinoma. The
      chemosensitivity against 5-FU, SN-38, MMC and CDDP was independent of MDR1
      C3435T, MRP1 G2168A, and MRP2 C-24T (C3972T), possibly due to no association with
      the growth rate of and mRNA expression levels of MDR1, MRP1 and MRP2 in the
      adenocarcinoma, however, MDR1 C3435T tended to be accompanied with a higher
      expression of MDR1 mRNA.

PMID- 16107776
TI  - Lack of survival advantage in patients with advanced, resectable squamous cell
      carcinoma of the oral cavity receiving induction chemotherapy with cisplatin
      (CDDP), docetaxel (TXT) and 5-fluorouracil (5FU).
AB  - Cisplatin-based neoadjuvant chemotherapy (NAC) has been reported to increase
      survival of patients with nasopharyngeal carcinoma, and organ preservation in
      those with laryngeal carcinoma, but its efficacy for other head and neck
      carcinomas is still controversial. We examined the effects of NAC for patients
      with stage III-IV squamous cell carcinoma of the oral cavity. The patients were
      divided into two groups; 9 patients who underwent NAC consisting of one course of
      cisplatin (CDDP), docetaxel (TXT) and 5-fluorouracil (5FU) followed by surgery
      (NAC group), and 18 patients who underwent surgery alone (control group).
      Complete response (CR) was not observed, but partial response (PR) was obtained
      in 6 of 9 patients (33%) of the NAC group. The 3-year survival rate was 29.6% in
      the NAC group and 81.5% in the control group. Although any valid conclusions
      could not be drawn because of the small number of patients examined here, NAC
      with CDDP, TXT and 5FU offered no advantages over standard treatment for advanced
      oral cancer in terms of survival.

PMID- 16107777
TI  - International Dyslexia Association's official journal 'Annals of dyslexia'.

PMID- 16107778
TI  - Poor readers of Chinese respond slower than good readers in phonological, rapid
      naming, and interval timing tasks.
AB  - The role of information processing deficits in poor readers of nonalphabetic
      scripts such as Chinese is not well documented. Here, we examined perceptual
      processing in good and poor readers of Chinese. Specifically, two groups of third
      grade children comprising 20 "good readers" and 19 "poor readers," drawn from a
      larger pool of 254 students, were tested using an auditory version of the Stop
      Reaction Time (Stop-RT) interval timing task, a phoneme perception task, and
      several measures of phonological awareness and orthographic processing. Mean Stop
      RTs for good readers were significantly faster than those for poor readers, and
      good readers were also faster in a test of rapid digit naming, but good and poor
      readers did not differ on measures of phoneme onset awareness or orthographic
      processing. Although good and poor readers did not differ in overall categorical
      perception of /pa5/ and /pha5/ stimuli, the good readers responded significantly
      faster than the poor readers. Taken together, the group differences obtained here
      are consistent with a slowing of information processing and behavioral output in
      poor readers of Chinese, rather than a loss of temporal resolution of perceptual
      processing.

PMID- 16107779
TI  - Does a visual-orthographic deficit contribute to reading disability?
AB  - In this study, visual-orthographic skills were defined as the ability to
      recognize whether letters and numerals are correctly oriented. Aims were to
      investigate whether visual-orthographic skills would contribute independent
      variance to reading, and whether children with a visual-orthographic deficit
      would be more impaired readers than similar children without this deficit.
      Participants were 207 children, aged 8 to 10 years, who attended school in a
      small suburban community. Because of the evidence that phonological awareness and
      naming speed are strongly related to reading, visual-orthographic skills were
      entered into hierarchical regression analyses following these variables. With
      age, verbal IQ, and verbal short-term memory also controlled, visual-orthographic
      skills accounted for significant independent variance in all reading measures.
      When children with a visual- orthographic deficit (29% of the sample) were
      compared with those without this deficit, they were significantly lower on all
      reading variables. At 8 to 10 years of age, reading progress of some children
      continues to be hampered by a problem in orthographic memory for the orientation
      of letters and numerals. Such children will require special attention, but their
      problems may be overlooked. As recommended by Willows and Terepocki (1993), there
      is need for further research on the phenomenon of letter reversals when they
      occur among children beyond first grade.

PMID- 16107780
TI  - The inadequacy of Individual Educational Program (IEP) goals for high school
      students with word-level reading difficulties.
AB  - This investigation analyzed goals from the Individual Educational Programs (IEPs)
      of 54 high school students with diagnosed reading disabilities in basic skills
      (decoding and/or word identification). Results showed that for 73% of the
      students, the IEPs written when they were in high school failed to specify any
      objectives regarding their acute difficulties with basic skills. IEPs from
      earlier points in the students' educations were also reviewed, as available. For
      23 of the students, IEPs were present in the students' files for three time
      points: elementary school (ES), middle school (MS), and high school (HS). Another
      20 students from the sample of 54 had IEPs available for two time points (HS and
      either MS or ES). Comparisons with the IEPs from younger years showed a pattern
      of decline from ES to MS to HS in the percentage of IEPs that commented on or set
      goals pertaining to weaknesses in decoding. These findings suggest that basic
      skills deficits that persist into the upper grade levels are not being
      sufficiently targeted for remediation, and help explain why older students
      frequently fail to resolve their reading problems.

PMID- 16107781
TI  - Acquired dyslexia in a Turkish-English speaker.
AB  - The Turkish script is characterised by completely transparent bidirectional
      mappings between orthography and phonology. To date, there has been no reported
      evidence of acquired dyslexia in Turkish speakers leading to the naive view that
      reading and writing problems in Turkish are probably rare. We examined the extent
      to which phonological impairment and orthographic transparency influence reading
      disorders in a native Turkish speaker. BRB is a bilingual Turkish-English speaker
      with deep dysphasia accompanied by acquired dyslexia in both languages. The main
      findings are an effect of imageability on reading in Turkish coincident with
      surface dyslexia in English and preserved nonword reading. BRB's acquired
      dyslexia suggests that damage to phonological representations might have a
      consequence for learning to read in Turkish. We argue that BRB's acquired
      dyslexia has a common locus in chronic underactivation of phonological
      representations in Turkish and English. Despite a common locus, reading problems
      manifest themselves differently according to properties of the script and the
      type of task.

PMID- 16107782
TI  - Effects of mora deletion, nonword repetition, rapid naming, and visual search
      performance on beginning reading in Japanese.
AB  - This study examined the extent to which mora deletion (phonological analysis),
      nonword repetition (phonological memory), rapid automatized naming (RAN), and
      visual search abilities predict reading in Japanese kindergartners and first
      graders. Analogous abilities have been identified as important predictors of
      reading skills in alphabetic languages like English. In contrast to English,
      which is based on grapheme-phoneme relationships, the primary components of
      Japanese orthography are two syllabaries-hiragana and katakana (collectively
      termed "kana")-and a system of morphosyllabic symbols (kanji). Three RAN tasks
      (numbers, objects, syllabary symbols [hiragana]) were used with kindergartners,
      with an additional kanji RAN task included for first graders. Reading measures
      included accuracy and speed of passage reading for kindergartners and first
      graders, and reading comprehension for first graders. In kindergartners, hiragana
      RAN and number RAN were the only significant predictors of reading accuracy and
      speed. In first graders, kanji RAN and hiragana RAN predicted reading speed,
      whereas accuracy was predicted by mora deletion. Reading comprehension was
      predicted by kanji RAN, mora deletion, and nonword repetition. Although number
      RAN did not contribute unique variance to any reading measure, it correlated
      highly with kanji RAN. Implications of these findings for research and practice
      are discussed.

PMID- 16107783
TI  - Atypical reactions associated with heroin use--five states, January-April 2005.
AB  - Heroin use typically produces a well-recognized syndrome of euphoria, miosis, and
      respiratory and central nervous system depression; cardiovascular effects are not
      a common finding. In January 2005, a man aged 21 years in New Jersey was
      hospitalized with an atypical reaction (e.g., tachycardia and palpitations) after
      reported heroin use. During the next 3 months, 25 additional persons in five
      states were reported to poison control centers (PCCs) and local public health
      agencies with a similar reaction after reported heroin use; in all, 24 of 26
      patients were hospitalized. Analysis of drug specimens or testing of urine was
      performed in certain cases; in eight patients, the veterinary pharmaceutical
      clenbuterol was detected. This report describes four representative cases and
      summarizes the investigation by state and local health and law enforcement
      authorities and CDC into the 26 cases of atypical reactions after heroin use
      reported in five states (Connecticut, New Jersey, New York, North Carolina, and
      South Carolina) during January 28-April 17, 2005. Unintentional or intentional
      adulteration of illicit drugs such as cocaine or heroin is an additional
      potential hazard associated with their use.

PMID- 16107784
TI  - Mercury exposure--Kentucky, 2004.
AB  - In November 2004, a student aged 15 years brought a small vial of liquid mercury
      onto a school bus and into a high school in Kentucky. A subsequent investigation
      revealed that mercury had been in the student's possession for more than a year
      and that substantial amounts had been spilled in multiple locations. This report
      describes the results of that investigation, which indicated that 1) duration of
      exposure was associated with the amount of mercury absorbed by exposed persons
      and 2) extensive multiagency collaboration facilitated an efficient response. The
      investigation further revealed that, although mercury exposure is common,
      clinicians might not be aware of how to evaluate and treat patients with mercury
      exposure. State and federal health agencies should provide schools, clinicians,
      and local health department staff with readily accessible guidelines for use in
      mercury spills and exposures.

PMID- 16107785
TI  - Update: interim guidance for minimizing risk for human lymphocytic
      choriomeningitis virus infection associated with pet rodents.
AB  - In May 2005, CDC received reports of illness in four solid-organ transplant
      recipients who were later determined to have been infected with lymphocytic
      choriomeningitis virus (LCMV) from a common organ donor. Three of the four organ
      recipients died, 23-27 days after transplantation. This report updates
      information about the ongoing investigation and provides interim measures for
      reducing the risk for LCMV infection from pet rodents associated with this
      outbreak.

PMID- 16107786
TI  - Memantine reduces hematoma expansion in experimental intracerebral hemorrhage,
      resulting in functional improvement.
AB  - Glutamate is accumulated in abundance during the early period of experimental
      hematoma, and the activation of N-methyl-D-aspartate (NMDA) receptors by
      glutamate can result in an influx of calcium and neuronal death in cases of
      intracerebral hemorrhage (ICH). Memantine, which is known to be a moderate
      affinity, uncompetitive, NMDA receptor antagonist, was investigated with regard
      to its ability to block the glutamate overstimulation and tissue plasminogen
      activator (tPA)/urokinase plasminogen activator (uPA)/matrix metalloproteinase
      (MMP)-9 modulation in experimental ICH. Intracerebral hemorrhage was induced via
      the infusion of collagenase into the left basal ganglia of adult rats. Either
      memantine (20 mg/kg/day) or PBS was intraperitoneally administered 30 min after
      the induction of ICH, and, at daily intervals afterwards, for either 3 or 14
      days. Hemorrhage volume decreased by 47% in the memantine group, as compared with
      the ICH-only group. In the memantine group, the numbers of TUNEL+,
      myeloperoxidase (MPO)+, and OX42+ cells decreased in the periphery of the
      hematoma. Memantine resulted in an upregulation of bcl-2 expression and an
      inhibition of caspase-3 activation. Memantine also exerted a profound inhibitory
      effect on the upregulation of tPA/uPA mRNA, and finally decreased the MMP-9 level
      in the hemorrhagic brain. In modified limb-placing test, the memantine-treated
      rats exhibited lower scores initially, and recovered more quickly and thoroughly
      throughout the 35 days of the study. Here, we show that memantine causes a
      reduction of hematoma expansion, coupled with an inhibitory effect on the tPA/uPA
      and MMP-9 level. Subsequently, memantine was found to reduce inflammatory
      infiltration and apoptosis, and was also determined to induce functional recovery
      after ICH.

PMID- 16107787
TI  - Permanent focal brain ischemia induces isoform-dependent changes in the pattern
      of Na+/Ca2+ exchanger gene expression in the ischemic core, periinfarct area, and
      intact brain regions.
AB  - Dysregulation of sodium [Na+]i and calcium [Ca2+]i homeostasis plays a pivotal
      role in the pathophysiology of cerebral ischemia. Three gene products of the
      sodium-calcium exchanger family NCX1, NCX2, and NCX3 couple, in a bidirectional
      way, the movement of these ions across the cell membrane during cerebral
      ischemia. Each isoform displays a selective distribution in the rat brain. To
      determine whether NCX gene expression can be regulated after cerebral ischemia,
      we used NCX isoform-specific antisense radiolabeled probes to analyze, by
      radioactive in situ hybridization histochemistry, the pattern of NCX1, NCX2, and
      NCX3 transcripts in the ischemic core, periinfarct area, as well as in
      nonischemic brain regions, after 6 and 24 h of permanent middle cerebral artery
      occlusion (pMCAO) in rats. We found that in the focal region, comprising
      divisions of the prefrontal, somatosensory, and insular cortices, all three NCX
      transcripts were downregulated. In the periinfarct area, comprising part of the
      motor cortex and the lateral compartments of the caudate-putamen, NCX2 messenger
      ribonucleic acid (mRNA) was downregulated, whereas NCX3 mRNA was significantly
      upregulated. In remote nonischemic brain regions such as the prelimbic and
      infralimbic cortices, and tenia tecta, both NCX1 and NCX3 transcripts were
      upregulated, whereas in the medial caudate-putamen only NCX3 transcripts
      increased. In all these intact regions, NCX2 signal strongly decreased. These
      results indicate that NCX gene expression is regulated after pMCAO in a
      differential manner, depending on the exchanger isoform and region involved in
      the insult. These data may provide a better understanding of each NCX subtype's
      pathophysiologic role and may allow researchers to design appropriate
      pharmacological strategies to treat brain ischemia.

PMID- 16107790
TI  - Plasma leptin and antipsychotic-induced body weight gain.

PMID- 16107794
TI  - Ratings games.

PMID- 16107793
TI  - WntD is a feedback inhibitor of Dorsal/NF-kappaB in Drosophila development and
      immunity.
AB  - Regulating the nuclear factor-kappaB (NF-kappaB) family of transcription factors
      is of critical importance to animals, with consequences of misregulation that
      include cancer, chronic inflammatory diseases and developmental defects. Studies
      in Drosophila melanogaster have proved fruitful in determining the signals used
      to control NF-kappaB proteins, beginning with the discovery that the Toll/NF
      kappaB pathway, in addition to patterning the dorsal-ventral axis of the fly
      embryo, defines a major component of the innate immune response in both
      Drosophila and mammals. Here, we characterize the Drosophila wntD (Wnt inhibitor
      of Dorsal) gene. We show that WntD acts as a feedback inhibitor of the NF-kappaB
      homologue Dorsal during both embryonic patterning and the innate immune response
      to infection. wntD expression is under the control of Toll/Dorsal signalling, and
      increased levels of WntD block Dorsal nuclear accumulation, even in the absence
      of the IkappaB homologue Cactus. The WntD signal is independent of the common Wnt
      signalling component Armadillo (beta-catenin). By engineering a gene knockout, we
      show that wntD loss-of-function mutants have immune defects and exhibit increased
      levels of Toll/Dorsal signalling. Furthermore, the wntD mutant phenotype is
      suppressed by loss of zygotic dorsal. These results describe the first secreted
      feedback antagonist of Toll signalling, and demonstrate a novel Wnt activity in
      the fly.

PMID- 16107796
TI  - Climate for progress.

PMID- 16107795
TI  - Science and religion in harmony.

PMID- 16107798
TI  - Synthetic biologists face up to security issues.

PMID- 16107799
TI  - NASA draws up blueprint for craft to reach Moon and Mars.

PMID- 16107801
TI  - Climate sceptics place bets on world cooling down.

PMID- 16107800
TI  - Warming debate highlights poor data.

PMID- 16107802
TI  - Survey questions safety of alternative medicine.

PMID- 16107804
TI  - Kansas backs lessons critical of evolution.

PMID- 16107805
TI  - WHO urges regional offices to stockpile flu drug for staff.

PMID- 16107806
TI  - Index aims for fair ranking of scientists.

PMID- 16107808
TI  - International Space Station: testing times.

PMID- 16107809
TI  - Complex systems: order out of chaos.

PMID- 16107810
TI  - Deep-sea biology: the life aquatic.

PMID- 16107811
TI  - Drug firms back-pedal on direct advertising.

PMID- 16107814
TI  - Answering the critics of Japanese whale research.

PMID- 16107815
TI  - Power-plant design should prepare for carbon capture.

PMID- 16107816
TI  - Buddhism is no bar to an open mind. Is science?

PMID- 16107817
TI  - Re-wilding North America.

PMID- 16107822
TI  - Cosmology: original questions.

PMID- 16107821
TI  - Biodiversity: turning up the heat on hotspots.

PMID- 16107823
TI  - Atmospheric chemistry: natural bleach under scrutiny.

PMID- 16107825
TI  - Astrophysics: swift progress.

PMID- 16107824
TI  - Cell biology: Shaggy mouse tales.

PMID- 16107827
TI  - Cardiology: rips repaired.

PMID- 16107828
TI  - Conservation biology: lion attacks on humans in Tanzania.
AB  - Large carnivores inspire opposition to conservation efforts owing to their impact
      on livestock and human safety. Here we analyse the pattern of lion attacks over
      the past 15 years on humans in Tanzania, which has the largest population of
      lions in Africa, and find that they have killed more than 563 Tanzanians since
      1990 and injured at least 308. Attacks have increased dramatically during this
      time: they peak at harvest time each year and are most frequent in areas with few
      prey apart from bush pigs (Potamochoerus larvatus), the most common nocturnal
      crop pest. Our findings provide an important starting point for devising
      strategies to reduce the risk to rural Tanzanians of lion attacks.

PMID- 16107829
TI  - Brownian motion: absolute negative particle mobility.
AB  - Noise effects in technological applications, far from being a nuisance, can be
      exploited with advantage - for example, unavoidable thermal fluctuations have
      found application in the transport and sorting of colloidal particles and
      biomolecules. Here we use a microfluidic system to demonstrate a paradoxical
      migration mechanism in which particles always move in a direction opposite to the
      net acting force ('absolute negative mobility') as a result of an interplay
      between thermal noise, a periodic and symmetric microstructure, and a biased
      alternating-current electric field. This counterintuitive phenomenon could be
      used for bioanalytical purposes, for example in the separation and fractionation
      of colloids, biological molecules and cells.

PMID- 16107831
TI  - Unscrambling hepatitis C virus-host interactions.
AB  - The human suffering exacted by the hepatitis C virus is enormous. Hundreds of
      thousands of people die each year from liver failure and cancer caused by this
      infection. There is no vaccine, and the available antiviral drugs are toxic,
      expensive and only partly effective. Progress has been hindered by the absence of
      cell culture and small-animal models of the infection. Nonetheless, recent
      advances have yielded several promising new antiviral drugs and enhanced the
      prospects of developing a vaccine. The recent development of a robust in vitro
      hepatitis C virus infection system will aid this search.

PMID- 16107832
TI  - Unravelling hepatitis C virus replication from genome to function.
AB  - Since the discovery of the hepatitis C virus over 15 years ago, scientists have
      raced to develop diagnostics, study the virus and find new therapies. Yet
      virtually every attempt to dissect this pathogen has met with roadblocks that
      impeded progress. Its replication was restricted to humans or experimentally
      infected chimpanzees, and efficient growth of the virus in cell culture failed
      until very recently. Nevertheless hard-fought progress has been made and the
      first wave of antiviral drugs is entering clinical trials.

PMID- 16107833
TI  - Evasion of intracellular host defence by hepatitis C virus.
AB  - Viral infection of mammalian cells rapidly triggers intracellular signalling
      events leading to interferon alpha/beta production and a cellular antiviral
      state. This 'host response' is our first line of immune defence against infection
      as it imposes several barriers to viral replication and spread. Hepatitis C virus
      (HCV) evades the host response through a complex combination of processes that
      include signalling interference, effector modulation and continual viral genetic
      variation. These evasion strategies support persistent infection and the spread
      of HCV. Defining the molecular mechanisms by which HCV regulates the host
      response is of crucial importance and may reveal targets for novel therapeutic
      strategies.

PMID- 16107834
TI  - Adaptive immune responses in acute and chronic hepatitis C virus infection.
AB  - The hepatitis C virus (HCV) persists in the majority of infected individuals and
      is a significant cause of human illness and death globally. Recent studies have
      yielded important insights into immunity to HCV, in particular revealing the
      central role of T cells in viral control and clearance. Other key features of
      adaptive immune responses remain obscure, including mechanisms by which T cells
      control HCV replication, the role of antibodies in conferring protection and how
      cellular and humoral immunity are subverted in persistent infection.

PMID- 16107835
TI  - Challenges and successes in developing new therapies for hepatitis C.
AB  - Hepatitis C virus (HCV) will continue to be a serious global health threat for
      many years to come because of the chronic nature of the infection, its high
      prevalence and the significant morbidity of the resulting disease. Recently, a
      small number of molecules have produced encouraging results in proof-of-concept
      clinical trials. At the same time, preclinical evidence is accumulating that
      development of resistance will eventually limit the efficacy of new drugs. Thus,
      combinations of multiple agents will be required to treat chronic HCV infection.

PMID- 16107836
TI  - Prospects for a vaccine against the hepatitis C virus.
AB  - The recent discovery of natural immunity to the hepatitis C virus and vaccine
      efficacy in the chimpanzee challenge model has allowed optimism about the
      development of at least a partly effective vaccine against this heterogeneous
      pathogen that is responsible for much of the chronic liver disease around the
      world. The immune systems of some infected individuals can spontaneously clear
      the virus, whereas other people need treatment with antivirals that work partly
      by stimulating humoral and cellular immune responses. Therefore, therapeutic
      vaccine strategies are also being pursued to improve treatment outcome.

PMID- 16107837
TI  - Mechanism of action of interferon and ribavirin in treatment of hepatitis C.
AB  - Since the identification of the hepatitis C virus, great strides have been made
      in the development of an antiviral therapy. As a crucial mediator of the innate
      antiviral immune response, interferon-alpha (IFN-alpha) was a natural choice for
      treatment. Whereas treatment with IFN-alpha alone achieved only modest success,
      the addition of the broad-spectrum antiviral agent ribavirin greatly improved
      responses. However, half of the infected individuals with chronic disease do not
      achieve sustained clearance of hepatitis C virus. To optimize current therapeutic
      strategies and to develop new therapies, a better understanding of the mechanism
      of action of IFN and ribavirin will be essential.

PMID- 16107838
TI  - Hepatitis C and liver transplantation.
AB  - Liver transplantation is a life-saving therapy to correct liver failure, portal
      hypertension and hepatocellular carcinoma arising from hepatitis C infection. But
      despite the successful use of living donors and improvements in immunosuppression
      and antiviral therapy, organ demand continues to outstrip supply and recurrent
      hepatitis C with accelerated progression to cirrhosis of the graft is a frequent
      cause of graft loss and the need for retransplantation. Appropriate selection of
      candidates and timing of transplantation, coupled with better pre- and post
      transplant antiviral therapy, are needed to improve outcomes.

PMID- 16107839
TI  - Exotoxin A-eEF2 complex structure indicates ADP ribosylation by ribosome mimicry.
AB  - The bacteria causing diphtheria, whooping cough, cholera and other diseases
      secrete mono-ADP-ribosylating toxins that modify intracellular proteins. Here, we
      describe four structures of a catalytically active complex between a fragment of
      Pseudomonas aeruginosa exotoxin A (ETA) and its protein substrate, translation
      elongation factor 2 (eEF2). The target residue in eEF2, diphthamide (a modified
      histidine), spans across a cleft and faces the two phosphates and a ribose of the
      non-hydrolysable NAD+ analogue, betaTAD. This suggests that the diphthamide is
      involved in triggering NAD+ cleavage and interacting with the proposed
      oxacarbenium intermediate during the nucleophilic substitution reaction,
      explaining the requirement of diphthamide for ADP ribosylation. Diphtheria toxin
      may recognize eEF2 in a manner similar to ETA. Notably, the toxin-bound betaTAD
      phosphates mimic the phosphate backbone of two nucleotides in a conformational
      switch of 18S rRNA, thereby achieving universal recognition of eEF2 by ETA.

PMID- 16107840
TI  - An unexpectedly rapid decline in the X-ray afterglow emission of long gamma-ray
      bursts.
AB  - 'Long' gamma-ray bursts (GRBs) are commonly accepted to originate in the
      explosion of particularly massive stars, which give rise to highly relativistic
      jets. Inhomogeneities in the expanding flow result in internal shock waves that
      are believed to produce the gamma-rays we see. As the jet travels further outward
      into the surrounding circumstellar medium, 'external' shocks create the afterglow
      emission seen in the X-ray, optical and radio bands. Here we report observations
      of the early phases of the X-ray emission of five GRBs. Their X-ray light curves
      are characterised by a surprisingly rapid fall-off for the first few hundred
      seconds, followed by a less rapid decline lasting several hours. This steep
      decline, together with detailed spectral properties of two particular bursts,
      shows that violent shock interactions take place in the early jet outflows.

PMID- 16107841
TI  - Young chondrules in CB chondrites from a giant impact in the early Solar System.
AB  - Chondrules, which are the major constituent of chondritic meteorites, are
      believed to have formed during brief, localized, repetitive melting of dust
      (probably caused by shock waves) in the protoplanetary disk around the early Sun.
      The ages of primitive chondrules in chondritic meteorites indicate that their
      formation started shortly after that of the calcium-aluminium-rich inclusions
      (4,567.2 +/- 0.7 Myr ago) and lasted for about 3 Myr, which is consistent with
      the dissipation timescale for protoplanetary disks around young solar-mass stars.
      Here we report the 207Pb-206Pb ages of chondrules in the metal-rich CB (Bencubbin
      like) carbonaceous chondrites Gujba (4,562.7 +/- 0.5 Myr) and Hammadah al Hamra
      237 (4,562.8 +/- 0.9 Myr), which formed during a single-stage, highly energetic
      event. Both the relatively young ages and the single-stage formation of the CB
      chondrules are inconsistent with formation during a nebular shock wave. We
      conclude that chondrules and metal grains in the CB chondrites formed from a
      vapour-melt plume produced by a giant impact between planetary embryos after dust
      in the protoplanetary disk had largely dissipated. These findings therefore
      provide evidence for planet-sized objects in the earliest asteroid belt, as
      required by current numerical simulations of planet formation in the inner Solar
      System.

PMID- 16107842
TI  - Experimental measurement of the photonic properties of icosahedral quasicrystals.
AB  - Quasicrystalline structures may have optical bandgap properties-frequency ranges
      in which the propagation of light is forbidden-that make them well-suited to the
      scientific and technological applications for which photonic crystals are
      normally considered. Such quasicrystals can be constructed from two or more types
      of dielectric material arranged in a quasiperiodic pattern whose rotational
      symmetry is forbidden for periodic crystals (such as five-fold symmetry in the
      plane and icosahedral symmetry in three dimensions). Because quasicrystals have
      higher point group symmetry than ordinary crystals, their gap centre frequencies
      are closer and the gaps widths are more uniform-optimal conditions for forming a
      complete bandgap that is more closely spherically symmetric. Although previous
      studies have focused on one-dimensional and two-dimensional quasicrystals, where
      exact (one-dimensional) or approximate (two-dimensional) band structures can be
      calculated numerically, analogous calculations for the three-dimensional case are
      computationally challenging and have not yet been performed. Here we circumvent
      the computational problem by doing an experiment. Using stereolithography, we
      construct a photonic quasicrystal with centimetre-scale cells and perform
      microwave transmission measurements. We show that three-dimensional icosahedral
      quasicrystals exhibit sizeable stop gaps and, despite their quasiperiodicity,
      yield uncomplicated spectra that allow us to experimentally determine the faces
      of their effective Brillouin zones. Our studies confirm that they are excellent
      candidates for photonic bandgap materials.

PMID- 16107843
TI  - Liquid crystal 'blue phases' with a wide temperature range.
AB  - Liquid crystal 'blue phases' are highly fluid self-assembled three-dimensional
      cubic defect structures that exist over narrow temperature ranges in highly
      chiral liquid crystals. The characteristic period of these defects is of the
      order of the wavelength of visible light, and they give rise to vivid specular
      reflections that are controllable with external fields. Blue phases may be
      considered as examples of tuneable photonic crystals with many potential
      applications. The disadvantage of these materials, as predicted theoretically and
      proved experimentally, is that they have limited thermal stability: they exist
      over a small temperature range (0.5-2 degrees C) between isotropic and chiral
      nematic (N*) thermotropic phases, which limits their practical applicability.
      Here we report a generic family of liquid crystals that demonstrate an unusually
      broad body-centred cubic phase (BP I*) from 60 degrees C down to 16 degrees C. We
      prove this with optical texture analysis, selective reflection spectroscopy,
      Kossel diagrams and differential scanning calorimetry, and show, using a simple
      polarizer-free electro-optic cell, that the reflected colour is switched
      reversibly in applied electric fields over a wide colour range in typically 10
      ms. We propose that the unusual behaviour of these blue phase materials is due to
      their dimeric molecular structure and their very high flexoelectric coefficients.
      This in turn sets out new theoretical challenges and potentially opens up new
      photonic applications.

PMID- 16107844
TI  - Short-term variations in the oxidizing power of the atmosphere.
AB  - The hydroxyl radical is the predominant atmospheric oxidant, responsible for
      removing a wide range of trace gases, including greenhouse gases, from the
      atmosphere. Determination of trends and variability in hydroxyl radical
      concentrations is critical to understanding whether the 'cleansing' properties of
      the atmosphere are changing. The variability in hydroxyl radical concentrations
      on annual to monthly timescales, however, is difficult to quantify. Here we show
      records of carbon monoxide containing radiocarbon (14CO), which is oxidized by
      hydroxyl radicals, from clean-air sites at Baring Head, New Zealand, and Scott
      Base, Antarctica, spanning 13 years. Using a model study, we correct for known
      variations in production of 14CO (refs 6, 7), allowing us to exploit this species
      as a diagnostic for short term changes in hydroxyl radical concentrations. We
      find no significant long-term trend in hydroxyl radical concentrations but
      provide evidence for recurring short-term variations of around ten per cent
      persisting for a few months. We also find decreases in hydroxyl radical
      concentrations of up to 20 per cent, apparently triggered by the eruption of Mt
      Pinatubo in 1991 and by the occurrence of extensive fires in Indonesia in 1997.

PMID- 16107845
TI  - In situ Os isotopes in abyssal peridotites bridge the isotopic gap between MORBs
      and their source mantle.
AB  - Abyssal peridotites are assumed to represent the mantle residue of mid-ocean
      ridge basalts (MORBs). However, the osmium isotopic compositions of abyssal
      peridotites and MORB do not appear to be in equilibrium, raising questions about
      the cogenetic relationship between those two reservoirs. However, the cause of
      this isotopic mismatch is mainly due to a drastic filtering of the data based on
      the possibility of osmium contamination by sea water. Here we present a detailed
      study of magmatic sulphides (the main carrier of osmium) in abyssal peridotites
      and show that the 187Os/188Os ratio of these sulphides is of primary mantle
      origin and can reach radiogenic values suggesting equilibrium with MORB. Thus,
      the effect of sea water on the osmium systematics of abyssal peridotites has been
      overestimated and consequently there is no true osmium isotopic gap between MORBs
      and abyssal peridotites.

PMID- 16107846
TI  - Earthquake rupture dynamics frozen in exhumed ancient faults.
AB  - Most of our knowledge about co-seismic rupture propagation is derived from
      inversion and interpretation of strong-ground-motion seismograms, laboratory
      experiments on rock and rock-analogue material, or inferred from theoretical and
      numerical elastodynamic models. However, additional information on dynamic
      rupture processes can be provided by direct observation of faults exhumed at the
      Earth's surface. Pseudotachylytes (solidified friction-induced melts) are the
      most certain fault-rock indicator of seismicity on ancient faults. Here we show
      how the asymmetry in distribution and the orientation of pseudotachylyte-filled
      secondary fractures around an exhumed fault can be used to reconstruct the
      earthquake rupture directivity, rupture velocity and fracture energy, by
      comparison with the theoretical dynamic stress field computed around propagating
      fractures. In particular, the studied natural network of pseudotachylytes is
      consistent with a dominant propagation direction during repeated seismic events
      and subsonic rupture propagation close to the Rayleigh wave velocity.

PMID- 16107847
TI  - Silurian brachiopods with soft-tissue preservation.
AB  - 'Articulated' rhynchonelliformean brachiopods are abundant shelly fossils, but
      the direct fossil record of their soft parts was hitherto confined to a single
      pyritized trace possibly representing a lophophore. Anatomical knowledge of
      extinct rhynchonelliformeans relies heavily on analogies to extant species; these
      analogies are untested for stem-group clades. The Silurian Herefordshire (UK)
      Konservat-Lagerstatte (about 425 Myr bp) yields exceptionally preserved three
      dimensional fossils that provide unrivalled insights into the palaeobiology of a
      variety of invertebrates. The fossils are preserved as calcitic void in-fills in
      carbonate concretions within a volcaniclastic horizon, and are reconstructed
      digitally. Here we describe a stem-group rhynchonelliformean specimen from this
      deposit; it most probably belongs in the order Orthida. A robust ridged pedicle
      with distal rootlets is preserved, together with a lophophore and other soft
      tissue structures. The pedicle morphology is novel, urging caution in inferring
      stem-group rhynchonelliformean anatomy from that of crown-group species. Smaller
      brachiopods are attached to the specimen; these include a probable atrypide, with
      pedicle and marginal setae preserved.

PMID- 16107848
TI  - Global hotspots of species richness are not congruent with endemism or threat.
AB  - Biodiversity hotspots have a prominent role in conservation biology, but it
      remains controversial to what extent different types of hotspot are congruent.
      Previous studies were unable to provide a general answer because they used a
      single biodiversity index, were geographically restricted, compared areas of
      unequal size or did not quantitatively compare hotspot types. Here we use a new
      global database on the breeding distribution of all known extant bird species to
      test for congruence across three types of hotspot. We demonstrate that hotspots
      of species richness, threat and endemism do not show the same geographical
      distribution. Only 2.5% of hotspot areas are common to all three aspects of
      diversity, with over 80% of hotspots being idiosyncratic. More generally, there
      is a surprisingly low overall congruence of biodiversity indices, with any one
      index explaining less than 24% of variation in the other indices. These results
      suggest that, even within a single taxonomic class, different mechanisms are
      responsible for the origin and maintenance of different aspects of diversity.
      Consequently, the different types of hotspots also vary greatly in their utility
      as conservation tools.

PMID- 16107849
TI  - Local translation of RhoA regulates growth cone collapse.
AB  - Neuronal development requires highly coordinated regulation of the cytoskeleton
      within the developing axon. This dynamic regulation manifests itself in axonal
      branching, turning and pathfinding, presynaptic differentiation, and growth cone
      collapse and extension. Semaphorin 3A (Sema3A), a secreted guidance cue that
      primarily functions to repel axons from inappropriate targets, induces
      cytoskeletal rearrangements that result in growth cone collapse. These effects
      require intra-axonal messenger RNA translation. Here we show that transcripts for
      RhoA, a small guanosine triphosphatase (GTPase) that regulates the actin
      cytoskeleton, are localized to developing axons and growth cones, and this
      localization is mediated by an axonal targeting element located in the RhoA 3'
      untranslated region (UTR). Sema3A induces intra-axonal translation of RhoA mRNA,
      and this local translation of RhoA is necessary and sufficient for Sema3A
      mediated growth cone collapse. These studies indicate that local RhoA translation
      regulates the neuronal cytoskeleton and identify a new mechanism for the
      regulation of RhoA signalling.

PMID- 16107850
TI  - ERM is required for transcriptional control of the spermatogonial stem cell
      niche.
AB  - Division of spermatogonial stem cells produces daughter cells that either
      maintain their stem cell identity or undergo differentiation to form mature
      sperm. The Sertoli cell, the only somatic cell within seminiferous tubules,
      provides the stem cell niche through physical support and expression of surface
      proteins and soluble factors. Here we show that the Ets related molecule (ERM) is
      expressed exclusively within Sertoli cells in the testis and is required for
      spermatogonial stem cell self-renewal. Mice with targeted disruption of ERM have
      a loss of maintenance of spermatogonial stem cell self-renewal without a block in
      normal spermatogenic differentiation and thus have progressive germ-cell
      depletion and a Sertoli-cell-only syndrome. Microarray analysis of primary
      Sertoli cells from ERM-deficient mice showed alterations in secreted factors
      known to regulate the haematopoietic stem cell niche. These results identify a
      new function for the Ets family transcription factors in spermatogenesis and
      provide an example of transcriptional control of a vertebrate stem cell niche.

PMID- 16107851
TI  - Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis
      elegans.
AB  - The worm Caenorhabditis elegans is a model system for studying many aspects of
      biology, including host responses to bacterial pathogens, but it is not known to
      support replication of any virus. Plants and insects encode multiple Dicer
      enzymes that recognize distinct precursors of small RNAs and may act
      cooperatively. However, it is not known whether the single Dicer of worms and
      mammals is able to initiate the small RNA-guided RNA interference (RNAi)
      antiviral immunity as occurs in plants and insects. Here we show complete
      replication of the Flock house virus (FHV) bipartite, plus-strand RNA genome in
      C. elegans. We show that FHV replication in C. elegans triggers potent antiviral
      silencing that requires RDE-1, an Argonaute protein essential for RNAi mediated
      by small interfering RNAs (siRNAs) but not by microRNAs. This immunity system is
      capable of rapid virus clearance in the absence of FHV B2 protein, which acts as
      a broad-spectrum RNAi inhibitor upstream of rde-1 by targeting the siRNA
      precursor. This work establishes a C. elegans model for genetic studies of animal
      virus-host interactions and indicates that mammals might use a siRNA pathway as
      an antiviral response.

PMID- 16107852
TI  - RNA interference is an antiviral defence mechanism in Caenorhabditis elegans.
AB  - RNA interference (RNAi) is an evolutionarily conserved sequence-specific post
      transcriptional gene silencing mechanism that is well defined genetically in
      Caenorhabditis elegans. RNAi has been postulated to function as an adaptive
      antiviral immune mechanism in the worm, but there is no experimental evidence for
      this. Part of the limitation is that there are no known natural viral pathogens
      of C. elegans. Here we describe an infection model in C. elegans using the
      mammalian pathogen vesicular stomatitis virus (VSV) to study the role of RNAi in
      antiviral immunity. VSV infection is potentiated in cells derived from RNAi
      defective worm mutants (rde-1; rde-4), leading to the production of infectious
      progeny virus, and is inhibited in mutants with an enhanced RNAi response (rrf-3;
      eri-1). Because the RNAi response occurs in the absence of exogenously added VSV
      small interfering RNAs, these results show that RNAi is activated during VSV
      infection and that RNAi is a genuine antiviral immune defence mechanism in the
      worm.

PMID- 16107853
TI  - Conditional telomerase induction causes proliferation of hair follicle stem
      cells.
AB  - TERT, the protein component of telomerase, serves to maintain telomere function
      through the de novo addition of telomere repeats to chromosome ends, and is
      reactivated in 90% of human cancers. In normal tissues, TERT is expressed in stem
      cells and in progenitor cells, but its role in these compartments is not fully
      understood. Here we show that conditional transgenic induction of TERT in mouse
      skin epithelium causes a rapid transition from telogen (the resting phase of the
      hair follicle cycle) to anagen (the active phase), thereby facilitating robust
      hair growth. TERT overexpression promotes this developmental transition by
      causing proliferation of quiescent, multipotent stem cells in the hair follicle
      bulge region. This new function for TERT does not require the telomerase RNA
      component, which encodes the template for telomere addition, and therefore
      operates through a mechanism independent of its activity in synthesizing telomere
      repeats. These data indicate that, in addition to its established role in
      extending telomeres, TERT can promote proliferation of resting stem cells through
      a non-canonical pathway.

PMID- 16107854
TI  - Endonucleolytic processing of covalent protein-linked DNA double-strand breaks.
AB  - DNA double-strand breaks (DSBs) with protein covalently attached to 5' strand
      termini are formed by Spo11 to initiate meiotic recombination. The Spo11 protein
      must be removed for the DSB to be repaired, but the mechanism for removal is
      unclear. Here we show that meiotic DSBs in budding yeast are processed by
      endonucleolytic cleavage that releases Spo11 attached to an oligonucleotide with
      a free 3'-OH. Two discrete Spo11-oligonucleotide complexes were found in equal
      amounts, differing with respect to the length of the bound DNA. We propose that
      these forms arise from different spacings of strand cleavages flanking the DSB,
      with every DSB processed asymmetrically. Thus, the ends of a single DSB may be
      biochemically distinct at or before the initial processing step-much earlier than
      previously thought. SPO11-oligonucleotide complexes were identified in extracts
      of mouse testis, indicating that this mechanism is evolutionarily conserved.
      Oligonucleotide-topoisomerase II complexes were also present in extracts of
      vegetative yeast, although not subject to the same genetic control as for
      generating Spo11-oligonucleotide complexes. Our findings suggest a general
      mechanism for repair of protein-linked DSBs.

PMID- 16107856
TI  - High blood pressure is inversely related with the presence and extent of coronary
      collaterals.
AB  - Patients with hypertension have an increased case fatality during acute
      myocardial infarction (MI). Coronary collateral (CC) circulation has been
      proposed to reduce the risk of death during acute ischaemia. We determined
      whether and to which degree high blood pressure (BP) affects the presence and
      extent of CC circulation. A cross-sectional study in 237 patients (84% males),
      admitted for elective coronary angioplasty between January 1998 and July 2002,
      was conducted. Collaterals were graded with Rentrop's classification (grade 0-3).
      CC presence was defined as Rentrop-grade > or =1. BP was measured twice with an
      inflatable cuff manometer in seated position. Pulse pressure was calculated by
      systolic blood pressure (SBP)-diastolic blood pressure (DBP). Mean arterial
      pressure was calculated by DBP+1/3 x (SBP-DBP). Systolic hypertension was defined
      by a reading > or =140 mmHg. We used logistic regression with adjustment for
      putative confounders. SBP (odds ratio (OR) 0.86 per 10 mmHg; 95% confidence
      interval (CI) 0.73-1.00), DBP (OR 0.67 per 10 mmHg; 95% CI 0.49-0.93), mean
      arterial pressure (OR 0.73 per 10 mmHg; 95% CI 0.56-0.94), systolic hypertension
      (OR 0.49; 95% CI 0.26-0.94), and antihypertensive treatment (OR 0.53; 95% CI 0.27
      1.02), each were inversely associated with the presence of CCs. Also, among
      patients with CCs, there was a graded, significant inverse relation between
      levels of SBP, levels of pulse pressure, and collateral extent. There is an
      inverse relationship between BP and the presence and extent of CC circulation in
      patients with ischaemic heart disease.

PMID- 16107857
TI  - Dendritic cell therapy with interferon-alpha synergistically suppresses outgrowth
      of established tumors in a murine colorectal cancer model.
AB  - Both dendritic cell (DC)-based immunotherapy and interferon (IFN)-alpha therapy
      have been proved to have potent long-lasting antitumor effects. In anticipation
      of synergistic antitumor effects, we performed combination therapy with DCs and
      IFN-alpha gene-transduced murine colorectal cancer MC38 cells (MC38-IFN-alpha).
      DCs incubated with MC38-IFN-alpha, but not neomycin-resistance gene-transduced
      MC38 cells (MC38-Neo), effectively enhanced proliferation of allogeneic
      splenocytes in vitro. In 12 of 17 mice, DCs in combination with MC38-IFN-alpha
      prevented the development of a parental tumor, while DCs and MC38-Neo did in only
      three of 17 mice (P=0.008). In a therapeutic model of an established parental
      tumor, inoculation of DCs and MC38-IFN-alpha suppressed the growth of the
      established parental tumors significantly compared with the administration of DCs
      with MC38-Neo or naive splenocytes with MC38-IFN-alpha (P=0.016 and 0.024,
      respectively). Analyses of immunohistochemistry and tumor-infiltrating
      mononuclear cells showed that CD8(+), CD11c(+), and NK1.1(+) cells markedly
      infiltrated the established tumors of mice treated with DCs and MC38-IFN-alpha.
      From the results of observation of parental tumor outgrowth in immune cell
      depleted mice, CD8(+) cells, and asialo-GM-1(+) cells were thought to contribute
      to the antitumor effects induced by the combination therapy. Furthermore, MC38
      specific cytolysis was detected when splenocytes of mice inoculated with DCs and
      MC38-IFN-alpha cells were stimulated with MC38-IFN-alpha cells in vitro. Since DC
      based immunotherapy in combination with IFN-alpha-expressing tumor cells induces
      potent antitumor cellular immune responses, it should be considered for clinical
      application.

PMID- 16107858
TI  - Characterization of HLA-A2-restricted HPV-16 E7-specific CD8(+) T-cell immune
      responses induced by DNA vaccines in HLA-A2 transgenic mice.
AB  - We have recently demonstrated that linkage of DNA-encoding calreticulin to DNA
      encoding human papillomavirus-16 E7 antigen strongly enhances the efficacy of DNA
      vaccines against E7-expressing tumors in animal models. In this study, as a
      prelude to clinical translation, we characterized the ability of DNA-encoding
      calreticulin linked to DNA-encoding E7 antigen to generate HLA-A2-restricted E7
      specific CD8(+) T-cell responses in HLA-A2 (AAD) transgenic mice, as well as
      antitumor effects against an E7(+) HLA-A2(+) tumor cell line, TC-1/A2. Our
      results show that while vaccination with CRT/E7 DNA generates strong H-2D(b)
      restricted E7 (amino acid (aa)49-57)-specific CD8(+) T-cell immune responses in
      both C57BL/6 and HLA-A2 (AAD) transgenic mice, no such responses were generated
      to HLA-A2-restricted epitopes in either type of mouse. In contrast, vaccination
      with DNA-encoding calreticulin linked to DNA encoding a mutant version of E7 with
      a deleted aa49-57 epitope leads to the generation of an HLA-A2-restricted E7
      (aa11-20)-specific CTL response in HLA-A2 (AAD) transgenic mice. More
      importantly, vaccination with CRT/mtE7 (del aa49-57) DNA protects against a
      lethal challenge with TC-1/A2 tumor cells in HLA-A2 (AAD) transgenic mice.
      Furthermore, our in vitro studies demonstrate that the presence of the E7 (aa49
      57) epitope does not suppress presentation of the HLA-A2-restricted E7 (aa11-20)
      epitope through MHC class I molecules. Thus, the predominant E7 aa49-57-specific
      CD8+ T-cell immune response in HLA-A2 transgenic mice vaccinated with CRT/E7 is
      likely due to preferred expansion of E7 aa49-57-specific CD8(+) T cells in
      vaccinated mice. These results highlight the importance of epitope
      immunodominance in the evaluation of immune responses in HLA-A2 (AAD) transgenic
      mice.

PMID- 16107860
TI  - An adenovirus vector with a chimeric fiber incorporating stabilized single chain
      antibody achieves targeted gene delivery.
AB  - Adenovirus (Ad) vectors are of utility for many therapeutic applications.
      Strategies have been developed to alter adenoviral tropism to achieve a cell
      specific gene delivery capacity employing fiber modifications allowing genetic
      incorporation of targeting motifs. In this regard, single chain antibodies (scFv)
      represent potentially useful agents to achieve targeted gene transfer. However,
      the distinct biosynthetic pathways that scFv and Ad capsid proteins are normally
      routed through have thus far been problematic with respect to scFv incorporation
      into the Ad capsid. Utilization of stable scFv, which also maintain correct
      folding and thus functionality under intracellular reducing conditions, could
      overcome this restriction. We genetically incorporated a stable scFv into a de
      knobbed, fibritin-foldon trimerized Ad fiber and demonstrated selective targeting
      to the cognate epitope expressed on the membrane surface of cells. We have shown
      that the scFv employed in this study retains functionality and that stabilizing
      the targeting molecule, per se, is critical to allow retention of antigen
      recognition in the adenovirus capsid-incorporated context.

PMID- 16107861
TI  - Efficient infection of tumor endothelial cells by a capsid-modified adenovirus.
AB  - Targeted antiangiogenic gene therapy is an attractive approach to treat
      metastatic cancer. However, the relative paucity of the receptors of the commonly
      used adenovirus serotype 5 in endothelial cells as compared with liver cells
      undermines the use of this vector for targeting the endothelial cells in tumors.
      To overcome this problem, we analyzed the ability of a hybrid Ad5/35 virus, where
      the serotype 5 fiber has been replaced with the fiber from serotype 35, to target
      tumor vasculature. Infection of human umbilical vein endothelial cells (HUVECs)
      with Ad5/35 at MOI 120 infected 100% of cells. In contrast, infection with Ad5 at
      the same MOI infected only 10% HUVECs. Ad5/35 was even more effective in
      transducing human aortic endothelial cells (HAECs), as infection with Ad5/35 at
      MOI 3.6 was sufficient to transduce 95% of cells. Gene expression analyses
      demonstrated that infection of HUVECs and HAECs with Ad5/35 resulted in between 1
      and 3 orders of magnitude higher gene expression than infection with Ad5.
      Furthermore, various liver-derived cells were less infectable with Ad5/35 than
      Ad5, indicating a favorable toxicity profile for this virus. In a rat colon
      carcinoma tumor model, Ad5 was located mainly in the liver parenchyma after
      hepatic artery administration. In contrast, Ad5/35 was found only in the
      angiogenesis-rich border region of the tumor. Double immunostaining revealed that
      Ad5/35 colocalized with CD31 and Flk-1 positive endothelial cells. These results
      indicate that Ad5/35 may be useful in anticancer strategies targeting tumor
      endothelial cells.

PMID- 16107863
TI  - Noninvasive monitoring of therapeutic gene transfer in animal models of muscular
      dystrophies.
AB  - Muscular dystrophies are a genetically and phenotypically heterogeneous group of
      degenerative muscle diseases. A subset of them are due to genetic deficiencies in
      proteins which form the dystrophin-associated complex at the membrane of the
      myofibers. In this report, we utilized recombinant adeno-associated virus
      containing a U7 cassette carrying an antisense sequence aimed at inducing exon
      skipping of the dystrophin gene or containing the alpha-sarcoglycan gene to
      alleviate the dystrophic phenotype of the mdx and Sgca-null mice, respectively.
      As these diseases are characterized by cycle of degeneration/regeneration, we
      postulated that a reporter gene coadministered at the time of the treatment would
      make it possible to follow the extent of muscle repair. We observed that the
      murine secreted alkaline phosphatase (muSeAP) level was very much lower in these
      animal models than in normal mice. Upon treatment of the dystrophic muscle by
      gene transfer, the level of muSeAP was restored and correlated with the
      expression of the therapeutic transgene and with the level of muscle improvement.
      The system described here provides a simple and noninvasive procedure for
      monitoring the outcome of a therapeutic strategy involving cell survival.

PMID- 16107864
TI  - DNA vaccination with an insulin construct and a chimeric protein binding to both
      CTLA4 and CD40 ameliorates type 1 diabetes in NOD mice.
AB  - Type 1 diabetes (T1D), a T-cell-mediated autoimmune disease, could be attributed
      to many defects in nonobese diabetic (NOD) mice, including deficient expressions
      of costimulatory molecules that impair antigen presentation. Thus, this deficient
      antigen presentation may result in a reduced ability to induce a tolerogenic
      response through negative selection/regulation of autoreactive T cells.
      Improperly activated T cells seem to be able to induce autoimmune responses
      causing diabetes. To re-establish tolerance to autoantigens by modulating
      costimulation, we constructed and tested a new type of DNA vaccine encoding a
      membrane-bound preproinsulin (mbPPI) and a chimeric gene vector encoding mutant
      B7.1/CD40L (mB7.1/CD40L) fusion protein. This mutant B7.1 binds CTLA4 but not
      CD28. We report that young NOD mice immunized with mbPPI along with mB7.1/CD40L
      DNA vectors significantly reduced diabetes incidence while treatment with
      CTLA4/IgG1 exacerbated diabetes. In conclusion, the combination of mbPPI and
      mB7.1/CD40L was able to protect against autoimmunity and diabetes in NOD mice
      possibly by promoting a more efficient presentation of autoantigen PPI and
      inducing specific tolerance to PPI by negatively regulating autoreactive T cells.

PMID- 16107865
TI  - Optimization of adenovirus-mediated endothelial nitric oxide synthase delivery in
      rat hindlimb ischemia.
AB  - Adenovirus-mediated overexpression of endothelial nitric oxide synthase (eNOS)
      induces collateral artery development and substantially increases blood flow
      after induction of experimental acute hindlimb ischemia. However, the optimal
      technique of gene delivery for this or any other form of gene therapy in limb
      ischemia is still unknown. The purpose of this study was to determine the effect
      of the two most commonly used techniques, intra-arterial and intramuscular
      injection, on blood flow recovery, collateral artery development, and
      preservation of muscle mass. We compared intra-arterial injection under vascular
      isolation, intra-arterial injection under transient vascular occlusion, and
      intramuscular injection of phosphate buffered saline (PBS) or adenovirus encoding
      either the eNOS (AdeNOS) or LacZ (AdlacZ) gene after induction of acute hindlimb
      ischemia. Delivery of AdeNOS by both intra-arterial injection techniques
      increased eNOS activity (22.30 versus 10.56, P<0.01), blood flow (0.90+/-0.02
      versus 0.69+/-0.07, P<0.001) and collateral artery development (17.56484 versus
      13.74259, P<0.05) more than by intramuscular delivery. Intra-arterial injection
      under transient vascular occlusion led to better preservation of muscle mass,
      muscle architecture, and clinical ischemic index, but led to greater transgene
      expression in distant organs and contralateral limb muscles. Intra-arterial
      injection of AdeNOS under transient vascular occlusion is the optimal technique
      to reverse severe hindlimb ischemia in the rat. This is the first systematic
      comparison of different delivery techniques used in gene therapy of experimental
      hindlimb ischemia.

PMID- 16107866
TI  - Safety and efficacy of citalopram in the treatment of premature ejaculation: a
      double-blind placebo-controlled, fixed dose, randomized study.
AB  - We evaluate the efficacy and safety of citalopram, a potent and highly selective
      serotonin reuptake inhibitor (SSRI) antidepressant, in patients with premature
      ejaculation (PE). In total, 58 potent men with PE were included in the study.
      Patients were randomly assigned to receive 20 mg oral daily citalopram (group 1,
      n = 29) or placebo (group 2, n = 29), during a 12-week period for each agent.
      Pretreatment evaluation included history and physical examination, intravaginal
      ejaculatory latency time (IVELT) evaluation, International Index of Erectile
      Function (IIEF) and Meares-Stamey test. The efficacy of two treatments was
      assessed every 2 weeks during treatment, at the end of study and in 3- and 6
      month follow-up after cessation of treatment, using responses to IIEF, IVELT
      evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and
      adverse drug effects. The trial was completed by 51 (88%) men. Analysis revealed
      a difference in the evolution of IVELT delay over time (P < 0.001). The IVELT
      after citalopram and placebo gradually increased from 32 and 28 s to
      approximately 268 and 38 s, respectively. The mean weekly intercourse episodes
      increased from pretreatment values of 1.3 and 1.2 to 2.4 and 1.4, for citalopram
      and placebo, respectively (P < 0.05). Baseline mean intercourse satisfaction
      domain values of IIEF 10 and 11 reached to 16 and 10 at 12-week treatment in
      groups 1 and 2, respectively (P < 0.05). Mean IVELT in group 1 was 210 and 198 s
      at 3- and 6-month follow-up, while in group 2 it was 27 and 25 s (P < 0.001),
      respectively. At 3- and six-month intercourse satisfaction domain values of IIEF
      were 15 and 14 in group 1 and 10 and 10 (P < 0.05) in group 2, respectively.
      Group 1 patients reported a significantly higher number of intercourse episodes
      per week (P < 0.05). Mean number of adverse events was 12 for citalopram and 4
      for placebo (P < 0.05). In conclusion, these results indicate that citalopram has
      significantly better results in terms of IVELT and intercourse satisfaction
      versus placebo. Further studies with different dosages and treatment regimens are
      necessary to draw final conclusions on the efficacy of this drug in PE and to
      prolong the efficacy.

PMID- 16107867
TI  - Epistaxis after PDE-5 inhibitors misuse.
AB  - A 32-year-old male presented to our department for recurrent epistaxis during
      sexual intercourses. The patient controlled the bleeding each time with sponge
      packs and gauzes. During the consultation, he volunteered that the trigger for
      the epistaxis appeared to have been misuse of phosphodiesterase (PDE)-5
      inhibitors, Viagra and Cialis. This first report of epistaxis after PDE-5
      inhibitors in a young patient underline the possibility that in the next years
      the number of similar cases might increase due to the diffusion of PDE-5
      inhibitor misuse in recreational settings.

PMID- 16107868
TI  - Early use of vacuum constriction device following radical prostatectomy
      facilitates early sexual activity and potentially earlier return of erectile
      function.
AB  - To assess the efficacy of vacuum constriction devices (VCD) following radical
      prostatectomy (RP) and determine whether early use of VCD facilitates early
      sexual activity and potentially earlier return of erectile function. This
      prospective study consisted of 109 patients who underwent nerve-sparing (NS) or
      non-nerve-sparing (NNS) RP between August 1999 and October 2001 and developed
      erectile dysfunction following surgery. The patients were randomized to VCD use
      daily for 9 months (Group 1, N=74) or observation without any erectogenic
      treatment (Group 2, N=35). Treatment efficacy was analyzed by responses to the
      Sexual Health Inventory of Men (SHIM) (abridged 5-item International Index of
      Erectile Function (IIEF-5)), which were stratified by the NS status. Patient
      outcome regarding compliance, change in penile length, return of natural
      erection, and ability for vaginal intercourse were also assessed. The mean
      patient age was 58.2 years, and the minimum follow-up was 9 months. Use of VCD
      began at an average of 3.9 weeks after RP. In Group 1, 80% (60/74) successfully
      used their VCD with a constriction ring for vaginal intercourse at a frequency of
      twice/week with an overall spousal satisfaction rate of 55% (33/60). In all, 19
      of these 60 patients (32%) reported return of natural erections at 9 months, with
      10/60 (17%) having erections sufficient for vaginal intercourse. The abridged
      IIEF-5 score significantly increased after VCD use in both the NS and NNS groups.
      After a mean use of 3 months, 14/74 (18%) discontinued treatment. In Group 2, 37%
      (13/35) of patients regained spontaneous erections at a minimum follow-up of 9
      months after surgery. However, only four of these patients (29%) had erections
      sufficient for successful vaginal intercourse and rest of patients (71%) sought
      adjuvant treatment. Of the 60 successful users, 14 (23%) reported a decrease in
      penile length and circumference at 9 months (range, 4-8 months) compared to 12/14
      (85%) among the nonresponders. However, in control group 22/35 reported decrease
      in penile length and circumference. Early use of VCD following RP facilitates
      early sexual intercourse, early patient/spousal sexual satisfaction, and
      potentially an earlier return of natural erections sufficient for vaginal
      penetration.

PMID- 16107869
TI  - Current status of genetics research in inflammatory bowel disease.
AB  - The research on genetic susceptibility of inflammatory bowel diseases (IBD) has
      been tremendous and over 10 chromosomal regions have been identified by genome
      wide scanning. Further fine mapping as well as candidate gene studies have
      already led to the identification of a number of susceptibility genes including
      CARD15, DLG5, OCTN1 and 2, NOD1, HLA, and TLR4. The CARD15 gene is undoubtedly
      replicated most widely and most understood at present. CARD15 is involved in the
      recognition of bacterial peptidoglycan-derived muramyl dipeptide (MDP) and will
      stimulate secretion of antimicrobial peptides including alpha-defensins (also
      called cryptdins) to protect the host from invasion. Genetic research in IBD has
      advanced our understanding of the clinical heterogeneity of the disease and has
      started to tackle the complex interactions between genetic risk factors and
      environmental risk factors in IBD. Genes also interfere with the metabolization
      of drugs and may influence the clinical response and the drug-related toxicity.
      Interesting pharmacogenetic data with respect to steroids, azathioprine, and
      infliximab have been generated in IBD. Overall, it is anticipated that genetic
      markers in the future will be implemented in an integrated molecular diagnostic
      and prognostic approach of our patients.

PMID- 16107870
TI  - Finnish case-control and family studies support PTPN22 R620W polymorphism as a
      risk factor in rheumatoid arthritis, but suggest only minimal or no effect in
      juvenile idiopathic arthritis.
AB  - Several studies have identified the PTPN22 allelic variant 1858 C/T that encodes
      the R620W amino-acid change as a putative susceptibility factor in autoimmune
      diseases. The current study was undertaken to examine a large cohort of Finnish
      rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) subjects using
      both population control and, importantly, family-based association methods. The
      latter is particularly important when, as is the case for the 1858 C/T
      polymorphism, the frequency of the variant allele (T) differs in both major
      ancestral populations and in subpopulations. The analysis of rheumatoid factor
      positive 1030 RA probands from Finland provides strong support for association of
      this variant in both population studies (allele specific odds ratio (OR)=1.47,
      95% confidence interval (CI)=1.27-1.70, P=3 x 10(-7)) and in family studies
      (P<10(-6)). In contrast, no allelic association was seen with JIA (230 probands)
      and only weak evidence for a genotypic effect of 1858T homozygotes was observed
      in this population.

PMID- 16107871
TI  - Characterization of the human CD5 endogenous retrovirus-E in B lymphocytes.
AB  - All T lymphocytes and some B lymphocytes express CD5. This coreceptor is encoded
      by one gene that consists of 11 exons. We have previously described a B cell
      specific alternative exon 1, leading to the synthesis of a protein, devoid of
      leader peptide, and, therefore, retained in the cytoplasm. The novel exon 1
      originates from a human endogenous retrovirus (HERV) at a time interval between
      the divergence of New World monkeys from Old World monkeys, and prior to the
      divergence of humans from Old World monkeys. Based on sequence similarity to
      gamma-retroviruses, it was categorized as class I: based on the specificity of
      its primer binding site, it was allotted to the subclass E, and based on its
      location within the cd5 gene, named HERV-E.CD5. Alternative transcripts were
      detected in lymphoid organs including fetal liver (not adult liver), more
      particularly in CD5-negative cell surface B-1b than in CD5-positive cell surface
      B-1a, and not at all in B-2 cells. By alignment of 5' long terminal repeats, HERV
      E.CD5 was distinguished from similar proviruses. This could be central to the
      regulation of membrane expression of CD5 in human B lymphocytes, and, thereby, to
      the strength of the B-cell antigen receptor signaling.

PMID- 16107872
TI  - Low birth weight and preterm births: etiologic fraction attributable to prenatal
      drug exposure.
AB  - OBJECTIVES: To determine the factors that would increase the likelihood of
      outcomes: low birth weight (LBW), preterm births and intrauterine growth
      restriction (IUGR). STUDY DESIGN: Secondary data analysis from a multi-center
      study. Risk factors for each outcome were derived from logistic regression
      models. Odds ratios (OR), 95% confidence intervals, and population-attributable
      risk proportions (PAR%) were estimated. RESULTS: Prenatal cocaine exposure
      increased the likelihood of LBW (OR: 3.59), prematurity (OR: 1.25), and IUGR (OR:
      2.24). Tobacco, but not marijuana, significantly influenced these outcomes.
      Alcohol had an effect on LBW and IUGR. Etiologic fractions (PAR%) attributable to
      tobacco for LBW, prematurity, and IUGR were 5.57, 3.66, and 13.79%, respectively.
      With additional drug exposure including cocaine, estimated summary PAR% increased
      to 7.20% (LBW), 5.68% (prematurity), and 17.96% (IUGR). CONCLUSION: Disease
      burden for each outcome increases with each added drug exposure; however,
      etiologic fraction attributable to tobacco is greater than for cocaine.

PMID- 16107873
TI  - Rehospitalization of extremely low birth weight (ELBW) infants: are there
      racial/ethnic disparities?
AB  - BACKGROUND: Premature infants are at increased risk for rehospitalization after
      discharge from the hospital. Racial disparities are known to exist in pediatric
      health care. OBJECTIVE: To evaluate whether racial disparities exist in the
      proportion of extremely low birth weight (ELBW) infants rehospitalized prior to
      18 months corrected age and the causes of rehospitalization. METHODS: The
      National Institute of Child Health and Human Development Neonatal Research
      Network database was used to identify all ELBW infants (n=2446) who were born
      between November 1, 1998 and May 31, 2000 at the 14 participating centers and
      discharged alive (n=1591). Infants were seen at 18-22 months corrected age for
      followup. Data related to maternal variables, race, socioeconomic status, medical
      morbidities, insurance, and rehospitalizations were recorded from the medical
      record and parent interview. Logistic regression analyses were used to examine
      the relationship of race/ethnicity and rehospitalization while controlling for
      gestational age, gender, center, maternal education, family income,
      bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, ventriculoperitoneal
      (VP) shunt, respiratory syncytial virus (RSV) prophylaxis, and insurance type.
      RESULTS: In all, 1405 (88%) infants were evaluated at followup. The racial
      distribution of infants admitted, discharged, seen at followup, and
      rehospitalized were similar. Rehospitalization occurred at least once in 49% of
      the infants. In the logistic regression analyses, race was not a significant
      predictor for rehospitalization. The odds of rehospitalization were related to
      low family income, type of insurance, BPD, VP shunt, RSV prophylaxis, and center.
      CONCLUSION: Race was not a predominant variable in the risk of rehospitalization
      in this cohort of ELBW infants. Medical morbidities and low family income appear
      to be the major risk factors for rehospitalization.

PMID- 16107874
TI  - A randomized multicenter study to determine the efficacy of activity restriction
      for preterm labor management in patients testing negative for fetal fibronectin.
AB  - OBJECTIVE: To assess the impact of activity restriction (AR) on the incidence of
      preterm birth in women treated for preterm labor testing negative for fetal
      fibronectin (fFN). STUDY DESIGN: Women who were diagnosed with preterm labor and
      tocolyzed with magnesium sulfate were concurrently screened with fFN for the
      purpose of subsequent management. Included were consenting patients with negative
      fFN, gestational age 23 0/7-33 6/7 weeks, cervical dilation < or =3 cm, and
      minimal vaginal bleeding. Patients were randomized to AR or no AR. Primary study
      outcome was incidence of preterm delivery and interval from randomization to
      delivery. RESULTS: A total of 73 women with negative fFN were randomized (36 with
      AR, 37 without AR). The overall preterm birth rate was 40%, with 44.4% of
      patients with AR and 35.1% of patients without AR delivering preterm, p=0.478.
      CONCLUSION: Maternal AR did not impact pregnancy outcome. The incidence of
      preterm birth in symptomatic women testing fFN negative was higher than
      previously reported.

PMID- 16107875
TI  - CTCF binding and higher order chromatin structure of the H19 locus are maintained
      in mitotic chromatin.
AB  - Most of the transcription factors, RNA polymerases and enhancer binding factors
      are absent from condensed mitotic chromosomes. In contrast, epigenetic marks of
      active and inactive genes somehow survive mitosis, since the activity status from
      one cell generation to the next is maintained. For the zinc-finger protein CTCF,
      a role in interpreting and propagating epigenetic states and in separating
      expression domains has been documented. To test whether such a domain structure
      is preserved during mitosis, we examined whether CTCF is bound to mitotic
      chromatin. Here we show that in contrast to other zinc-finger proteins, CTCF
      indeed is bound to mitotic chromosomes. Mitotic binding is mediated by a portion
      of the zinc-finger DNA binding domain and involves sequence specific binding to
      target sites. Furthermore, the chromatin loop organized by the CTCF-bound,
      differentially methylated region at the Igf2/H19 locus can be detected in
      mitosis. In contrast, the enhancer/promoter loop of the same locus is lost in
      mitosis. This may provide a novel form of epigenetic memory during cell division.

PMID- 16107876
TI  - MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation.
AB  - MDM2 is a RING domain ubiquitin E3 ligase and a major regulator of the p53 tumor
      suppressor. MDM2 binds to p53, inactivates p53 transcription function, inhibits
      p53 acetylation, and promotes p53 degradation. Here, we present evidence that
      MDM2 interacts with the nuclear corepressor KAP1. The binding is mediated by the
      N-terminal coiled-coil domain of KAP1 and the central acidic domain of MDM2. KAP1
      stimulates formation of p53-HDAC1 complex and inhibits p53 acetylation by
      interacting with MDM2. Expression of KAP1 cooperates with MDM2 to promote p53
      ubiquitination and degradation. The tumor suppressor ARF competes with KAP1 in
      MDM2 binding; oncogene induction of ARF expression reduces MDM2-KAP1 interaction.
      Depletion of endogenous KAP1 expression by RNAi stimulates p53 transcriptional
      activity, sensitizes p53 response to DNA damage, and increases apoptosis.
      Therefore, MDM2 interaction with KAP1 contributes to p53 functional regulation.
      ARF may regulate p53 acetylation and stability in part by inhibiting KAP1-MDM2
      binding.

PMID- 16107877
TI  - Kar3 interaction with Cik1 alters motor structure and function.
AB  - Kar3, a kinesin-14 motor of Saccharomyces cerevisiae required for mitosis and
      karyogamy, reportedly interacts with Cik1, a nonmotor protein, via its central,
      predicted coiled coil. Despite this, neither Kar3 nor Cik1 homodimers have been
      observed in vivo. Here we show that Kar3 is a dimer in vitro by analytical
      ultracentrifugation. The motor domains appear as paired particles by rotary
      shadow electron microscopy (EM) and circular dichroism (CD) spectroscopy of the
      nonmotor region shows characteristics of helical structure, typical of coiled
      coils. Remarkably, the Kar3/Cik1 nonmotor region shows greater helicity by CD
      analysis and rotary-shadow EM reveals a stalk joined to one large or two smaller
      particles. The highly helical Kar3/Cik1 nonmotor region and visible stalk
      indicate that dimerization with Cik1 causes structural changes in Kar3. The Cik1
      and Kar3 stalk regions preferentially associate with one another rather than
      forming homodimers. Kar3/Cik1 moves on microtubules at 2-2.4 microm min(-1), 2-5
      fold faster than Kar3, and destabilizes microtubules at the lagging ends. Thus,
      structural changes in Kar3 upon dimerization with Cik1 alter the motor velocity
      and likely regulate Kar3 activity in vivo.

PMID- 16107878
TI  - C/EBPbeta cooperates with RB:E2F to implement Ras(V12)-induced cellular
      senescence.
AB  - In primary cells, overexpression of oncogenes such as Ras(V12) induces premature
      senescence rather than transformation. Senescence is an irreversible form of G1
      arrest that requires the p19ARF/p53 and p16INK4a/pRB pathways and may suppress
      tumorigenesis in vivo. Here we show that the transcription factor C/EBPbeta is
      required for Ras(V12)-induced senescence. C/EBPbeta-/- mouse embryo fibroblasts
      (MEFs) expressing Ras(V12) continued to proliferate despite unimpaired induction
      of p19ARF and p53, and lacked morphological features of senescent fibroblasts.
      Enforced C/EBPbeta expression inhibited proliferation of wild-type MEFs and also
      slowed proliferation of p19Arf-/- and p53-/- cells, indicating that C/EBPbeta
      acts downstream or independently of p19ARF/p53 to suppress growth. C/EBPbeta was
      unable to inhibit proliferation of MEFs lacking all three RB family proteins or
      wild-type cells expressing dominant negative E2F-1 and, instead, stimulated their
      growth. C/EBPbeta decreased expression of several E2F target genes and was
      associated with their promoters in chromatin immunoprecipitation assays,
      suggesting that C/EBPbeta functions by repressing genes required for cell cycle
      progression. C/EBPbeta is therefore a novel component of the RB:E2F-dependent
      senescence program activated by oncogenic stress in primary cells.

PMID- 16107879
TI  - Translocation of a long amino-terminal domain through ER membrane by following
      signal-anchor sequence.
AB  - Type I signal-anchor sequences mediate translocation of the N-terminal domain (N
      domain) across the endoplasmic reticulum (ER) membrane. To examine the
      translocation in detail, dihydrofolate reductase (DHFR) was fused to the N
      terminus of synaptotagmin II as a long N-domain. Translocation was arrested by
      the DHFR ligand methotrexate, which stabilizes the folding of the DHFR domain,
      and resumed after depletion of methotrexate. The targeting of the ribosome
      nascent chain complex to the ER requires GTP, whereas N-domain translocation does
      not require any nucleotide triphosphates. Significant translocation was observed
      even in the absence of a lumenal hsp70 (BiP). When the nascent polypeptide was
      released from the ribosomes after the membrane targeting, the N-domain
      translocation was suppressed and the nascent chain was released from the
      translocon. Ribosomes have a crucial role in maintaining the translocation
      intermediate state. The translocation of the DHFR domain was greatly impaired
      when it was separated from the signal-anchor sequence. Unfolding and
      translocation of the DHFR domain must be driven by the stroke of the signal
      anchor sequence into translocon.

PMID- 16107880
TI  - Fidelity of Dpo4: effect of metal ions, nucleotide selection and
      pyrophosphorolysis.
AB  - We report the crystal structures of a translesion DNA polymerase, Dpo4, complexed
      with a matched or mismatched incoming nucleotide and with a pyrophosphate product
      after misincorporation. These structures suggest two mechanisms by which Dpo4 may
      reject a wrong incoming nucleotide with its preformed and open active site.
      First, a mismatched replicating base pair leads to poor base stacking and
      alignment of the metal ions and as a consequence, inhibits incorporation. By
      replacing Mg2+ with Mn2+, which has a relaxed coordination requirement and
      tolerates misalignment, the catalytic efficiency of misincorporation increases
      dramatically. Mn2+ also enhances translesion synthesis by Dpo4. Subtle
      conformational changes that lead to the proper metal ion coordination may,
      therefore, be a key step in catalysis. Second, the slow release of pyrophosphate
      may increase the fidelity of Dpo4 by stalling mispaired primer extension and
      promoting pyrophosphorolysis that reverses the polymerization reaction. Indeed,
      Dpo4 has robust pyrophosphorolysis activity and degrades the primer strand in the
      presence of pyrophosphate. The correct incoming nucleotide allows DNA synthesis
      to overcome pyrophosphorolysis, but an incorrect incoming nucleotide does not.

PMID- 16107881
TI  - Anandamide acts as an intracellular messenger amplifying Ca2+ influx via TRPV1
      channels.
AB  - The endocannabinoid anandamide is able to interact with the transient receptor
      potential vanilloid 1 (TRPV1) channels at a molecular level. As yet, endogenously
      produced anandamide has not been shown to activate TRPV1, but this is of
      importance to understand the physiological function of this interaction. Here, we
      show that intracellular Ca2+ mobilization via the purinergic receptor agonist
      ATP, the muscarinic receptor agonist carbachol or the Ca(2+)-ATPase inhibitor
      thapsigargin leads to formation of anandamide, and subsequent TRPV1-dependent
      Ca2+ influx in transfected cells and sensory neurons of rat dorsal root ganglia
      (DRG). Anandamide metabolism and efflux from the cell tonically limit TRPV1
      mediated Ca2+ entry. In DRG neurons, this mechanism was found to lead to TRPV1
      mediated currents that were enhanced by selective blockade of anandamide cellular
      efflux. Thus, endogenous anandamide is formed on stimulation of metabotropic
      receptors coupled to the phospholipase C/inositol 1,4,5-triphosphate pathway and
      then signals to TRPV1 channels. This novel intracellular function of anandamide
      may precede its action at cannabinoid receptors, and might be relevant to its
      control over neurotransmitter release.

PMID- 16107882
TI  - The Bud14p-Glc7p complex functions as a cortical regulator of dynein in budding
      yeast.
AB  - Regulated interactions between microtubules (MTs) and the cell cortex control MT
      dynamics and position the mitotic spindle. In eukaryotic cells, the adenomatous
      polyposis coli/Kar9p and dynein/dynactin pathways are involved in guiding MT plus
      ends and MT sliding along the cortex, respectively. Here we identify Bud14p as a
      novel cortical activator of the dynein/dynactin complex in budding yeast. Bud14p
      accumulates at sites of polarized growth and the mother-bud neck during
      cytokinesis. The localization to bud and shmoo tips requires an intact actin
      cytoskeleton and the kelch-domain-containing proteins Kel1p and Kel2p. While
      cells lacking Bud14p function fail to stabilize the pre-anaphase spindle at the
      mother-bud neck, overexpression of Bud14p is toxic and leads to elongated astral
      MTs and increased dynein-dependent sliding along the cell cortex. Bud14p
      physically interacts with the type-I phosphatase Glc7p, and localizes Glc7p to
      the bud cortex. Importantly, the formation of Bud14p-Glc7p complexes is necessary
      to regulate MT dynamics at the cortex. Taken together, our results suggest that
      Bud14p functions as a regulatory subunit of the Glc7p type-I phosphatase to
      stabilize MT interactions specifically at sites of polarized growth.

PMID- 16107884
TI  - Myeloproliferative disorders: the centrosome connection.
AB  - Some myeloproliferative disorders (MPD) result from a reciprocal translocation
      that involves the FGFR1 gene and a partner gene. The event creates a chimeric
      gene that encodes a fusion protein with constitutive FGFR1 tyrosine kinase
      activity. FGFR1-MPD is a rare disease, but its study may provide interesting
      clues on different processes such as cell signalling, oncogenesis and stem cell
      renewal. Some partners of FGFR1 are centrosomal proteins. The corresponding
      oncogenic fusion kinases are targeted to the centrosome. Constitutive
      phosphorylation at this site may perturbate centrosome function and the cell
      cycle. Direct attack at this small organelle may be an efficient way for
      oncogenes to alter regulation of signalling for proliferation and survival and
      get rid of checkpoints in cell cycle progression. The same effect might be
      triggered by other fusion kinases in other MPD and non-MPD malignancies.

PMID- 16107885
TI  - Retinoid/arsenic combination therapy of promyelocytic leukemia: induction of
      telomerase-dependent cell death.
AB  - Acute promyelocytic leukemia (APL) is efficiently treated with a cell
      differentiation inducer, all-trans retinoic acid (ATRA). However, a significant
      percentage of patients still develop resistance to this treatment. Recently,
      arsenic trioxide (As2O3), alone or in combination with ATRA, has been identified
      as an alternative therapy in patients with both ATRA-sensitive and ATRA-resistant
      APL. Previous investigations restricted the mechanism of this synergism to the
      modulation and/or degradation of PML-RARalpha oncoprotein through distinct
      pathways. In this study, using several ATRA maturation-resistant APL cell lines,
      we demonstrate in vitro that the success of ATRA/As2O3 treatment in APL pathology
      can be explained, at least in part, by a synergistic effect of these two drugs in
      triggering downregulation of telomerase efficient enough to cause telomere
      shortening and subsequent cell death. Such long-term low-dose combinatorial
      therapy strategies, developed also to avoid acute side effects, reinforce the
      notion that the antitelomerase strategy, based on a combination of active agents,
      should now be considered and evaluated not only in APL but also in other
      malignancies.

PMID- 16107883
TI  - G1 checkpoint failure and increased tumor susceptibility in mice lacking the
      novel p53 target Ptprv.
AB  - In response to DNA damage, p53 activates a G1 cell cycle checkpoint, in part
      through induction of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). Here
      we report the identification of a new direct p53 target, Ptprv (or ESP), encoding
      a transmembrane tyrosine phosphatase. Ptprv transcription is dramatically and
      preferentially increased in cultured cells undergoing p53-dependent cell cycle
      arrest, but not in cells undergoing p53-mediated apoptosis. This observation was
      further confirmed in vivo using a Ptprv null-reporter mouse line. A p53
      responsive element is present in the Ptprv promoter and p53 is recruited to this
      site in vivo. Importantly, while p53-dependent apoptosis is intact in mice
      lacking Ptprv, Ptprv-null fibroblasts and epithelial cells of the small intestine
      are defective in G1 checkpoint control. Thus, Ptprv is a new direct p53 target
      and a key mediator of p53-induced cell cycle arrest. Finally, Ptprv loss enhances
      the formation of epidermal papillomas after exposure to chemical carcinogens,
      suggesting that Ptprv acts to suppress tumor formation in vivo.

PMID- 16107886
TI  - Common genetic variants in the interleukin-6 and chitotriosidase genes are
      associated with the risk for serious infection in children undergoing therapy for
      acute myeloid leukemia.
AB  - Infectious complications represent a substantial cause of morbidity and mortality
      in children undergoing therapy for acute myeloid leukemia (AML). Since it has
      been shown that alterations in innate immune pathways contribute to the risk for
      serious infections, we analyzed well-characterized variants in innate immune
      genes (TNF, IL6, IL8, MPO, CHIT, FCGR2A, TLR2, and TLR4) to determine their
      possible contribution to infectious complications during therapy for pediatric
      AML. The study population consisted of 168 North European Caucasian children
      enrolled on the clinical trial AML-BFM 93. We found an association between Gram
      negative bacterial infection and common, functional variants in two genes, IL6
      and CHIT. The risk for infection was significantly higher in children with the G
      allele in the IL6 promoter at -174 bp (P=0.026) and in patients with the H allele
      of CHIT (P=0.033). The promoter variant in IL6 has been shown to increase
      expression while the H allele disrupts both function and circulating levels. Our
      data suggest that variant alleles of both IL6 and CHIT could influence
      susceptibility to infection with Gram-negative bacteria in children undergoing
      therapy for AML. Follow-up studies, namely replication association studies and in
      vitro investigation of these common polymorphisms, are warranted to confirm these
      observations.

PMID- 16107887
TI  - ALK-positive diffuse large B-cell lymphoma with ALK-Clathrin fusion belongs to
      the spectrum of pediatric lymphomas.

PMID- 16107888
TI  - Chronic myeloid leukemia CD34+ cells have elevated levels of phosphatidylinositol
      3,4,5 trisphosphate (PtdIns(3,4,5)P3) and lack a PtdIns(3,4,5)P3 response to
      cytokines and chemotactic factors; effects reversed by imatinib.

PMID- 16107889
TI  - Translational study of vitamin D differentiation therapy of myeloid leukemia:
      effects of the combination with a p38 MAPK inhibitor and an antioxidant.
AB  - Human myeloid leukemia cell lines are induced to terminal differentiation into
      monocyte lineage by 1,25-dihydroxyvitamin D3 (1,25D3) or its analogs
      (deltanoids). However, translation of these findings to the clinic is limited by
      calcemic effects of deltanoids. Strategies to overcome this problem include
      combination of deltanoids with other compounds to induce differentiation at
      lower, noncalcemic, deltanoid concentrations. We previously showed that either
      carnosic acid, an antioxidant, or SB202190, a p38 MAPK inhibitor, increase the
      potency of 1,25D3 in the HL60 cell line. Here, we report that simultaneous
      addition of both these agents further increases differentiation potency of
      deltanoids in this cell line and in freshly obtained leukemic cells ex vivo.
      Activity of MAPK pathways showed that increased differentiation was associated
      with enhanced activity of JNK pathway in all responding cell subtypes. Our
      studies suggest that patients with CML or AML subtypes M2 and M4, but not M1, M3
      or M4eo, are particularly suitable for this combination therapy. We conclude that
      the established cell line HL60 presents a good model for some, but not all,
      subtypes of myeloid leukemia, and that the JNK pathway plays an important role in
      monocytic differentiation of human leukemic cells ex vivo, as well as in vitro.

PMID- 16107890
TI  - Reply to Gaipa et Al.

PMID- 16107891
TI  - Immunophenotypic modulation in childhood precursor-B-ALL can be mimicked in vitro
      and is related to the induction of cell death.

PMID- 16107892
TI  - CDK2 catalytic activity and loss of nuclear tethering of retinoblastoma protein
      in childhood acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. During
      cell cycle progression from the mid- to late G1 phase, mammalian cells traverse
      the restriction point, a transition from mitogen dependence to mitogen
      independence, regulated by retinoblastoma protein (Rb). Different cyclin
      dependent kinases (CDKs) sequentially phosphorylate and inactivate Rb, which is
      associated by a change in Rb's nuclear affinity and activation of E2F
      transcription. Here, we show by in vitro kinase assays that ALL extracts
      contained CDK2 catalytic activity. When liberation of Rb from cell nuclei was
      tested by immune precipitation of differential cell extractions and Western blot
      analysis, little Rb was associated with the nuclear compartment. Together with
      the immunocytochemical analysis at a single cell level that Rb was phosphorylated
      at serine 612 and threonine 821, sites known to be phosphorylated by CDK2, the
      data indicated the presence of CDK2 catalytic activity and loss of Rb's nuclear
      affinity in ALL cells. We conclude that most ALL cells reside at or beyond the
      restriction point. This could explain the resistance of ALL cells to
      differentiation induction.

PMID- 16107893
TI  - Gatekeeper pathways and cellular background in the pathogenesis and therapy of
      AML.
AB  - Acute myelogenous leukemia (AML) is characterized by the accumulation of immature
      cells due to disturbed differentiation and proliferation of the myeloid lineage.
      Genetic alterations affecting transcription factors and receptor tyrosine kinases
      have been identified in AML and causally linked to the disease. The goal of this
      review is to address the role of the different genetic alterations in self
      renewal and proliferation and to discuss the cellular background in which these
      events occur during the pathogenesis of AML. Data from AML samples, clinical
      studies and mouse models for AML will be used to support the different theories
      regarding the leukemogenesis of AML. Finally, this review wants to highlight the
      implication of these findings for the therapy of AML.

PMID- 16107894
TI  - Twenty years of Polish experience with three consecutive protocols for treatment
      of childhood acute myelogenous leukemia.
AB  - Until 1983, results of treatment of acute myelogenous leukemia (AML) in Poland
      with different regimens were very poor. In 1983, the Polish Pediatric
      Leukemia/Lymphoma Study Group introduced a unified treatment protocol--a modified
      version of BFM-83 protocol. This led to an increase in the curability of AML from
      15% to approximately 32%. In 1994, a modification was made: the high-risk
      patients (>5% blasts in bone marrow on day 15 of therapy and all M5 cases)
      received two additional cycles with intermediate-dose cytarabine (ID-ARAC). This
      led to a nonsignificant improvement in the 5-year event-free survival (EFS) rate
      from 32 to 36%. A new treatment protocol employing idarubicin in place of
      daunorubicin was introduced in 1998 and produced better initial responses,
      increase in the number of patients attaining remission after induction therapy
      and proportional increase of standard-risk patients. The probability of 5-year
      EFS (pEFS) for the whole group of patients increased from 36 to 47%. In standard-
      and high-risk groups, the 5-year pEFS was 62 and 33%, respectively. The
      probability of 5-year disease-free survival was 58% in the whole group, and there
      were no differences between risk groups. Unsatisfactory treatment results in
      children classified into the high-risk group are principally due to the low
      remission rate.

PMID- 16107895
TI  - CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA
      and BMI1 oncogenes.
AB  - The t(10;11)(p13;q14-21) is found in T-ALL and acute myeloid leukemia and fuses
      CALM (Clathrin-Assembly protein-like Lymphoid-Myeloid leukaemia gene) to AF10. In
      order to gain insight into the transcriptional consequences of this fusion,
      microarray-based comparison of CALM-AF10+ vs CALM-AF10- T-ALL was performed. This
      analysis showed upregulation of HOXA5, HOXA9, HOXA10 and BMI1 in the CALM-AF10+
      cases. Microarray results were validated by quantitative RT-PCR on an independent
      group of T-ALL and compared to mixed lineage leukemia-translocated acute
      leukemias (MLL-t AL). The overexpression of HOXA genes was associated with
      overexpression of its cofactor MEIS1 in CALM-AF10+ T-ALL, reaching levels of
      expression similar to those observed in MLL-t AL. Consequently, CALM-AF10+ T-ALL
      and MLL-t AL share a specific HOXA overexpression, indicating they activate
      common oncogenic pathways. In addition, BMI1, located close to AF10 breakpoint,
      was overexpressed only in CALM-AF10+ T-ALL and not in MLL-t AL. BMI1 controls
      cellular proliferation through suppression of the tumor suppressors encoded by
      the CDKN2A locus. This locus, often deleted in T-ALL, was conserved in CALM-AF10+
      T-ALL. This suggests that decreased CDKN2A activity, as a result of BMI1
      overexpression, contributes to leukemogenesis in CALM-AF10+ T-ALL. We propose to
      define a HOXA+ leukemia group composed of at least MLL-t, CALM-AF10 and HOXA-t
      AL, which may benefit from adapted management.

PMID- 16107896
TI  - Treatment strategy and results in children treated on three Dutch Childhood
      Oncology Group acute myeloid leukemia trials.
AB  - This report describes the long-term follow-up data of three consecutive Dutch
      Childhood Oncology Group acute myeloid leukemia (AML) protocols. A total of 303
      children were diagnosed with AML, of whom 209 were eligible for this report. The
      first study was the AML-82 protocol. Results were inferior (5-year probability of
      overall survival (pOS) 31%) to other available regimes. Study AML-87 was based on
      the BFM-87 protocol, with prophylactic cranial irradiation in high-risk patients
      only, and without maintenance therapy. This led to a higher cumulative incidence
      of relapse than that reported by the Berlin-Frankfurt-Munster (BFM), but survival
      was similar (5-year pOS 47%), suggesting successful retrieval at relapse. The
      subsequent study AML-92/94 consisted of a modified BFM-93 protocol, that is,
      without maintenance therapy and prophylactic cranial irradiation. However, all
      patients were to be transplanted (auto- or allogeneic), although compliance was
      poor. Antileukemic efficacy was offset by an increase in the cumulative incidence
      of nonrelapse mortality, especially in remission patients, and survival did not
      improve (5-year pOS 44%). Our results demonstrate that outcome in childhood AML
      is still unsatisfactory, and that further intensification of therapy carries the
      risk of enhanced toxicity. Our patients are currently included in the MRC AML
      studies, based on the results of their AML 10 trial.

PMID- 16107897
TI  - Treatment and long-term results in children with acute myeloid leukaemia treated
      according to the AIEOP AML protocols.
AB  - Since 1982, four consecutive studies on childhood acute myeloid leukaemia (AML)
      (namely LAM-82, -87, -87M and -92) have been conducted in Italy by the
      Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The
      induction therapy of the first three studies consisted of daunorubicin and
      cytarabine structured in a 3+7 backbone. In the most recent protocol (LAM92),
      patients received two induction courses including idarubicin, cytarabine and
      etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were
      included in LAM-87 and 87M studies. Postremissional therapy significantly changed
      over time, with an ever-increasing role given to stem cell transplantation (SCT).
      The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was
      comparable, whereas that of children treated according to LAM-92 study was
      significantly better (P<0.005). Either allogeneic or autologous SCT was employed
      as consolidation therapy in more than 75% of cases enrolled in this latter study.
      Patients enrolled in the LAM-92 study were stratified in standard and high-risk
      groups with different outcome (67 vs 47%, respectively, P=0.04). Altogether, the
      results obtained in these four studies have permitted a progressive refinement of
      treatment, contributing to the structure of the ongoing LAM-2002 protocol that
      stratifies patients according to the presence of definite genetic anomalies and
      response to induction therapy.

PMID- 16107898
TI  - Removing a polyp.

PMID- 16107899
TI  - Interferon-alpha-induced changes in metallothionein expression in liver biopsies
      from patients with chronic hepatitis C.
AB  - An association between reactive oxygen species and liver damage has been
      postulated in the course of hepatitis C virus (HCV) infection. Metallothionein
      (MT), induced by HCV core protein and interferon (IFN), plays a role in
      scavenging free radicals. MT expression in liver biopsies obtained from 21
      patients with chronic HCV infection before and after IFN-alpha therapy was
      investigated. Changes in Knodell histological activity index (HAI) scores, MT
      protein levels (immunohistochemistry), MT-I and MT-II messenger (m)RNA expression
      levels (in situ hybridization) and proliferating cell nuclear antigen (PCNA)
      labelling index were determined and compared in serial liver specimens. MT
      staining was clustered around the portal tracts with inflammatory cells and
      fibrosis. The pattern of MT protein before IFN-alpha therapy was similar in all
      patients, but was higher in IFN-sustained responders than in nonresponders after
      IFN-alpha therapy. HAI scores and PCNA labelling indexes were significantly
      reduced after IFN-alpha therapy. MT-II mRNA expression correlated positively with
      PCNA index before therapy and with HAI scores after therapy (P<0.05). No
      correlation was found between MT-I mRNA and HAI scores or PCNA index. The
      findings indicate that IFN-alpha-induced hepatic MT may participate in the
      therapeutic effects of IFN-alpha for HCV. In addition, MT-II mRNA expression may
      be involved in cell proliferation in the livers of patients with chronic HCV
      infection.

PMID- 16107900
TI  - A sampling of Canadian practice in managing nonvariceal upper gastrointestinal
      bleeding before recent guideline publication: is there room for improvement?
AB  - BACKGROUND: There are few recent published consensus guidelines regarding
      nonvariceal upper gastrointestinal bleeding. In 2003, the Canadian Association of
      Gastroenterology sponsored a set of 20 recommendations. AIM: To compare current
      Canadian clinical practice patterns with these most recent guidelines. METHODS:
      Data obtained from the Canadian Registry of patients with Upper Gastrointestinal
      Bleeding and Endoscopy (RUGBE), complemented by a questionnaire sent out to the
      18 participating RUGBE sites, were used to compare present practice with all 20
      guidelines. RESULTS: Only three RUGBE sites had an explicit written protocol for
      nonvariceal upper gastrointestinal bleeding, and only 40% of the sites had
      support staff available after hours. The Blatchford prognostic scale was not used
      routinely, and only one site used the Rockall score for risk stratification. Most
      patients classified as low-risk according to the literature had endoscopy within
      24 h and a median length of stay of two days compared with high-risk patients who
      underwent endoscopy approximately 4 h earlier, had a median length of stay of 4.3
      days and displayed a higher mortality. Nineteen per cent of all patients had a
      routine second-look endoscopy. Proton pump inhibitors were frequently used in the
      acute setting. Thirteen per cent of all patients rebled and only 34% of these
      received a second endoscopy. One-half of all patients were tested for
      Helicobacter pylori while in hospital, mostly by histology, and one-third of
      those who tested positive received H pylori eradication during their
      hospitalization. CONCLUSION: Compared with recommendations put forward in the new
      guidelines, clinical practice before guideline publication was variable. The
      future level of guideline adherence and patient outcome data should be quantified
      and monitored as the guidelines are disseminated.

PMID- 16107901
TI  - Clostridium difficile-associated diarrhea in 200 Canadian children.
AB  - OBJECTIVE: Clostridium difficile-associated diarrhea is a major problem in
      adults. The present study was conducted to assess risk factors and outcomes in
      children with C difficile-associated diarrhea. METHODS: Laboratory records at a
      university-affiliated pediatric hospital were reviewed for all C difficile toxin
      positive stools (cell culture cytotoxin assay) between 2000 and 2003. Charts on
      identified patients were reviewed. RESULTS: Two hundred patients with a diagnosis
      of C difficile-associated diarrhea were identified between February 2000 and
      November 2003. There were 107 males and 93 females (mean age 5.4 years; median
      age 2.6 years). Underlying factors were identified in 19% (12 patients underwent
      chemotherapy; seven patients had Crohn's disease; six were transplantation
      recipients; seven an immunodeficiency; four with Hirschsprung disease; two
      diagnoses of 'other'). Of the 200 identified patients, 149 (74.5%) had
      documentation of antibiotics in the previous two months (32 penicillins; 38
      cephalosporins; three clindamycin, nine other single-agent, 59 multiple; eight
      not specified), and 111 (55.5%) had been hospitalized in the previous month. The
      symptoms of C difficile-associated diarrhea included bloody stools in 12.5% and
      frequent watery stools in 79%. Hospitalization was required in 27 of 116
      outpatients; stay was prolonged in seven of the 84 patients already hospitalized.
      Fifty-five per cent received metronidazole, 34% were not treated, and treatment
      data were not available for the remainder. Recurrence occurred in 31% of those
      treated and retreatment consisted of vancomycin (15%), probiotics (15%) and
      cholestyramine (6%). No colectomies were required but two deaths occurred.
      CONCLUSIONS: The majority of pediatric patients developing symptomatic C
      difficile-associated diarrhea had antibiotic exposure or hospitalization within
      the previous one to two months. This is higher than previously reported. One
      third had spontaneous symptom resolution. For those treated, recurrence rates
      were high. Mortality was significantly lower than described in adults, in
      agreement with prior literature.

PMID- 16107902
TI  - Use of prebiotics for inflammatory bowel disease.
AB  - The relevance of diet in both the pathogenesis and the therapy of inflammatory
      bowel disease is an evolving science. Disturbance of intestinal microflora
      (dysbiosis) is putatively a key element in the environmental component causing
      inflammatory bowel disease. Prebiotics are among the dietary components used in
      an attempt to counteract dysbiosis. Such predominantly carbohydrate dietary
      components exert effects on the luminal environment by physicochemical changes
      through pH alteration, by production of short chain fatty acids and by
      selectively promoting putatively 'health-beneficial' bacteria. The present review
      elaborates on some of the background rationale and mechanisms on the use of
      prebiotics. Additionally, published animal and human trials are discussed.

PMID- 16107903
TI  - Percutaneous valve replacement: Fact or fiction?
AB  - Percutaneous catheter-based interventions are an emerging area in the treatment
      of valvular heart disease. Despite many limitations related to device technology,
      valve durability and stability, and anatomical obstacles, the early results of
      percutaneous catheter-based valve repair and replacement are promising. The
      procedures are currently aimed at high-risk patients who cannot undergo
      conventional surgical management. The first percutaneous heart valve replacement
      occurred in 2002 in the pulmonary position. Subsequently, the early experience in
      the literature has reported over 50 human cases. The anatomical complexities of
      the aortic root have made success more elusive for percutaneous aortic valve
      replacement. Only a few cases have been reported, with variable success
      described. Percutaneous mitral valve replacement has not been reported to date;
      however, clinical trials are underway evaluating catheter-based techniques of
      mitral valve repair. Present enthusiasm should be tempered because scarcely more
      than 100 patients worldwide have undergone percutaneous valve interventions.
      Nonetheless, it is inevitable that as technology develops to overcome the present
      limitations and develop safe and effective techniques, percutaneous heart valve
      repair and replacement will undoubtedly increase in frequency. Scrupulously
      designed clinical trials must be performed to definitively determine the short-
      and long-term results of these procedures as compared with the gold standard of
      open surgical repair, as well as to define the appropriate patient population
      that will benefit the most.

PMID- 16107904
TI  - Improving the care of Canadian adults with congenital heart disease.
AB  - Canadian children with congenital heart disease (CHD) have been well cared for in
      the past half-century. These childhood success stories have resulted in there now
      being approximately 100,000 Canadian adults with CHD. Few of these patients have
      been cured or have normal hearts, and most were left with problems that will need
      to be addressed later in life. Approximately 55,000 such patients need expert
      care because their conditions are so rare or complicated that cardiologists and
      other caregivers have not been trained to look after them. Moreover, these 55,000
      Canadians face premature mortality, the need for further surgery or the prospect
      of major complications. They need expert care to optimize the quality of their
      lives and to help them to avoid premature death. There is no plan for the care of
      these patients. When they reached 18 years of age, they were moved into an adult
      care system that does not understand them, does not care about them and has not
      provided for their care. Provincial and federal Ministries of Health have not yet
      taken an interest in these patients. Canadian professionals have taken important
      steps in support of adults with CHD. They established the Canadian Adult
      Congenital Heart Network, and they developed a National Care Plan and management
      guidelines for their care. They have also made important contributions to the
      scientific literature, advancing the care of these patients. Waiting lists are
      much too long for adult patients with CHD. There are serious local and regional
      obstacles to the care of these patients because there are no provincial or
      regional plans for their care. Cardiologists who treat adult patients with CHD
      cannot earn enough in a fee-for-service system. There are serious human resource
      problems in Canadian Adult Congenital Heart Network centres that need to be
      addressed. There also needs to be greater coordination and integration between
      the pediatric and adult systems that care for these patients. Adults with CHD
      desperately need the help of the Heart and Stroke Foundations, leaders in the
      Canadian health care community and, ultimately, the Ministries of Health to help
      them protect their health and access expert care when needed in a timely way. The
      promises offered to them as children must also be honoured in their adult years.

PMID- 16107905
TI  - A rare case of pulmonary vein sarcoma.
AB  - Pulmonary vein tumours are rare. They can cause significant morbidity and
      mortality. The present report discusses a rare case of pulmonary vein sarcoma in
      an elderly male patient.

PMID- 16107906
TI  - Temporal analysis of acute myocardial infarction in Ontario, Canada.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is a substantial cause of morbidity
      and mortality in Canada. Evidence suggests that the incidence and mortality of
      AMI increase in the winter. Determining the strength and nature of seasonality
      patterns in relation to age and sex may be helpful in health care planning.
      OBJECTIVES: To examine the seasonal patterns of AMI hospital admissions by age
      and sex, to assess the strength of the seasonal patterns and to examine the
      overall trends in admissions. METHODS: A retrospective population-based study was
      conducted to assess temporal patterns in 14 years of hospital admissions for AMI
      (from April 1, 1988, to March 31, 2002) in Ontario. Seasonality was assessed
      using the autoregression coefficient (R2Autoreg), and Fisher's Kappa and
      Bartlett's Kolmogorov-Smirnov tests. RESULTS: There were 271,321 people in the
      cohort, of whom 63% (n = 171,546) were male and 37% (n = 99,775) were female.
      There was an increase in AMI admissions since 1988 that reached a plateau in
      1992, which was attributable mostly to the increased rate in the oldest age
      groups (70 years and older), where admission rates more than doubled. An
      association between seasonality and AMI admissions was found in most age and sex
      groups, with men consistently exhibiting a stronger seasonality pattern. The
      greatest difference in the cohort, 2.5 per 100,000 per month (134 admissions),
      occurred between December and September (13.64 per 100,000 in September versus
      16.14 per 100,000 in December). CONCLUSIONS: AMI admissions show seasonality
      patterns, which are more pronounced in men. Although statistically significant,
      the seasonal differences are small in terms of absolute numbers, and are likely
      irrelevant in health care planning.

PMID- 16107907
TI  - Effect of hyperlipidemia on QT dispersion in patients without ischemic heart
      disease.
AB  - BACKGROUND: Lipoproteins are known to exert direct and indirect effects on
      cardiovascular function, but their effects on ventricular repolarization have not
      yet been clearly elucidated. OBJECTIVES: To assess the effect of hyperlipidemia
      on the longest QT interval (QTmax) of the 12-lead surface electrocardiogram (ECG)
      and on QT dispersion (QTd) in type IIb hyperlipidemic patients without myocardial
      ischemia, and to compare these patients with healthy control subjects. METHODS:
      Ninety-six hyperlipidemic patients (44 men and 52 women; mean age 53+/-13 years)
      and 101 healthy control subjects (43 men and 58 women; mean age 46+/-16 years)
      were examined. Total cholesterol, high density lipoprotein cholesterol, low
      density lipoprotein cholesterol (LDL-C), triglyceride, apolipoprotein (apo) A1,
      apo B, lipoprotein(a), QTmax and QTd were measured. According to heart rate,
      corrected QTmax and corrected QTd were also determined. RESULTS: A significant
      difference was observed between the two groups of subjects with respect to serum
      cholesterol, LDL-C, triglyceride, apo B, QTmax, corrected QTmax, QTd and
      corrected QTd. A positive significant correlation was found between cholesterol,
      triglyceride, LDL-C and all of the studied ECG parameters, between high density
      lipoprotein cholesterol and QTmax, apo B and QTd, and between body mass index and
      all of the studied ECG markers. CONCLUSIONS: Hyperlipidemia may have a direct
      effect on the studied ECG markers.

PMID- 16107908
TI  - The relationship between potency of oxidative stress and severity of dilated
      cardiomyopathy.
AB  - BACKGROUND: It has been suggested that oxidative stress may have a role in the
      etiopathogenesis of congestive heart failure. OBJECTIVES: To investigate and
      compare the oxidative-antioxidative status and oxidative stress index (OSI) of
      patients with idiopathic dilated cardiomyopathy (IDC) with those of healthy
      volunteers, and to determine the relationship between total antioxidant capacity
      (TAC) and ejection fraction (EF). METHODS: Twenty-eight patients with IDC and 24
      control subjects were enrolled in the study. Antioxidative status was evaluated
      by measuring the TAC and the vitamin C and thiol levels in the plasma. Oxidative
      status was evaluated by measuring the total peroxide level. The per cent ratio of
      TAC to total peroxide level was accepted as the OSI. EF was measured using
      Simpson's method. RESULTS: TAC and vitamin C and thiol levels of plasma were
      found to be significantly lower in patients with IDC than in control subjects (P
      < 0.001). In contrast, total peroxide levels and OSIs were significantly higher
      in patients with IDC than in control subjects (P = 0.002 and P = 0.002,
      respectively). An important positive correlation was found between TAC and EF (r
      = 0.772; P < 0.001). On the other hand, significant negative correlations were
      found between EF and OSI and between EF and total peroxide levels in patients.
      CONCLUSIONS: Oxidants are increased and antioxidants are decreased in patients
      with IDC; as a result, the oxidative-antioxidative balance is shifted to the
      oxidative side. There is a significant correlation between the potency of
      oxidative stress and the severity of IDC. It is believed that supplementation of
      antioxidants in the treatment of IDC may be helpful to these patients.

PMID- 16107909
TI  - Drug-induced long QT syndrome and torsade de pointes.
AB  - Several medications, including drugs prescribed for noncardiac indications, have
      been associated with a prolongation of the QT interval on the surface
      electrocardiogram. Under certain circumstances, this clinical manifestation may
      reflect an increased risk for patients presenting with a polymorphic ventricular
      tachycardia known as torsade de pointes. Drugs that prolong the QT interval
      belong to several pharmacological classes, but most of them share one
      pharmacological effect: they lengthen cardiac repolarization mostly by blocking
      specific cardiac K+ channels. The potent blocking of cardiac K+ channels and
      excessive lengthening of cardiac repolarization favour the development of
      membrane oscillations (early afterdepolarizations) due to Ca2+/Na+ re-entry.
      Early afterdepolarizations, when propagated, may trigger torsade de pointes. In
      addition to excessive lengthening of the QT interval, other predisposing factors
      to drug-induced torsade de pointes include bradycardia, electrolyte imbalance,
      female sex and genetic polymorphisms in various ion channel constituents. In
      brief, drug-induced torsade de pointes is a relatively rare event in the entire
      population, which nonetheless carries the risk of lethal consequences.
      Consequently, drug surveillance programs are very active in identifying drugs
      that induce the prolongation of the QT interval. Recent data have allowed us to
      better understand the underlying electrophysiological mechanisms of the syndrome
      and better identify predisposing factors.

PMID- 16107910
TI  - [French-Canadian validation of the MOS Social Support Survey].
AB  - BACKGROUND: The MOS Social Support Survey was developed for patients who
      participated in the Medical Outcomes Study (MOS), a two-year study on persons who
      suffered from chronic illness. There are a number of advantages to using the MOS
      Social Support Survey, especially with those persons who suffer from chronic
      illness: it is easy to understand, is relatively short, is multidimensional, can
      be completed by the patient without assistance and has good psychometric
      properties. OBJECTIVE: The goal of this study was to establish a French-Canadian
      version of the MOS Social Support Survey and to verify its psychometric
      properties following the cross-cultural translation and validation procedures
      proposed by Vallerand. METHODS: A first draft of the MOS Social Support Survey
      was achieved by following the back-to-back translation technique. Next, a
      committee of four bilingual people reviewed and evaluated the preliminary
      versions of the questionnaire (English and French) to establish a French
      experimental version. A pre-test was done with 10 francophone persons. The
      Haccoun method was used to evaluate the construct validity and test-retest
      reliability, as well as the internal consistency of the questionnaire. The test
      retest was performed with 20 students from the School of Languages from Laval
      University, Sainte-Foy, Quebec. The present research was approved by the ethics
      committee of the institution. RESULTS: The results showed acceptable internal
      consistency and good reliability. The psychometric properties were found to be
      acceptable and comparable with those obtained by Sherbourne and Stewart with the
      English version. CONCLUSION: The French-Canadian version of the MOS Social
      Support Survey should be useful in evaluating social support among patients to
      allow medical staff to plan rehabilitation programs that would include the
      necessary consultations and interventions needed to establish a better quality of
      life for the patient.

PMID- 16107911
TI  - Exercise-induced ST segment elevation in leads V1 to V3 due to proximal right
      coronary artery stenosis.

PMID- 16107912
TI  - Does sex influence the impact that smoking, treatment interruption and impaired
      pulmonary function have on outcomes in limited stage small cell lung cancer
      treatment?
AB  - PURPOSE: To look for survival differences between men and women with limited
      stage small cell lung cancer (LS-SCLC) by examining stratified variables that
      impair treatment efficacy. METHODS: A retrospective review of 215 LS-SCLC
      patients treated from 1989 to 1999 with concurrent chemotherapy-radiotherapy
      modelled on the 'early-start' thoracic radiotherapy arm of a National Cancer
      Institute of Canada randomized trial. RESULTS: Of 215 LS-SCLC patients, 126
      (58.6%) were men and 89 (41.4%) were women. Smoking status during treatment for
      186 patients (86.5%) was: 107 (58%) nonsmoking (NS) (76 [71%] male [M]; 31 [29%]
      female [F]) and 79 (42%) smoking (S) (36 M [46%]; 43 F [54%]) (continuing-to
      smoke F versus M, P=0.001). Fifty-six patients (26%) had radiotherapy
      interruptions (RTI) during chemotherapy-radiotherapy because of toxicity.
      Radiotherapy breaks were not associated with sex (P=0.95). Survival by sex and
      smoking status at two years was: F + NS = 38.7%; F + S = 21.6%; M + NS = 22.9%;
      and M + S = 9.1% (P=0.0046). Survival by sex and RTI status at two years was: F +
      no RTI = 32.4%; F + RTI = 23.6%; M + no RTI = 23.0%; and M + RTI = 3.8%
      (P=0.0025). Diffusion capacity for carbon monoxide (DLCO) was recorded for 86
      patients (40%) and median survival by sex and DLCO was F = 16.7 months and M =
      12.1 months for a DLCO less than 60%; and for a DLCO 60% or more, F = 15.1 months
      and M = 15.3 months. First relapses were recorded in 132 cases (61%), with chest
      failure in men (45%) greater than for women (35%) and cranial failure rates
      similar between sexes (48%). Upon multivariable analysis, continued smoking was
      the strongest negative factor affecting survival. CONCLUSIONS: In LS-SCLC, women
      overall do better than men, with or without a negative variable. The largest
      quantifiable improvement in survival for women came from smoking cessation, and
      for men from avoidance of breaks during treatment.

PMID- 16107913
TI  - The validity of diagnosing chronic obstructive pulmonary disease from a large
      administrative database.
AB  - BACKGROUND: Health authorities create and maintain administrative databases.
      Despite the potential advantages of these databases, the validity of the
      information they include must be considered. OBJECTIVE: To examine the validity
      of diagnosing chronic obstructive pulmonary disease (COPD) from a large
      administrative database. METHODS: Physician services and prescription claims data
      related to COPD and asthma were extracted from the Quebec universal medical
      insurance register (Regie de l'assurance-maladie du Quebec; RAMQ) from the period
      of April 1, 1994 to March 31, 1999. Before obtaining the data, criteria for the
      validity of the COPD diagnosis in the database were formulated based on the
      epidemiology of COPD in the province. The extent to which the database satisfied
      these criteria are described within the present paper. RESULTS: For patients aged
      65 years or older, COPD was two times more prevalent in the RAMQ database than in
      the 1994/1995 National Population Health Survey. One in three patients with a
      RAMQ-diagnosis of COPD also had a RAMQ-diagnosis of asthma, and 47% of patients
      aged 65 years or older with a RAMQ-diagnosis of COPD did not fill any
      prescription for beta-2-agonists. In addition, 42% of patients with a RAMQ
      diagnosis of COPD who never had a RAMQ-diagnosis of asthma appeared only once
      with that diagnosis in the database. Of all patients aged 65 years or older with
      a RAMQ-diagnosis of COPD, 37% and 23% met the operational definitions of
      'possible COPD' and 'probable COPD', respectively. CONCLUSIONS: Most RAMQ
      diagnoses of COPD lack validity; therefore, the validity of database diagnoses
      should be routinely ascertained before using administrative databases in clinical
      and health services research.

PMID- 16107914
TI  - Lung function measured by impulse oscillometry and spirometry following eucapnic
      voluntary hyperventilation.
AB  - BACKGROUND: The efficacy of impulse oscillometry (IOS) to measure airway calibre
      change is not fully established. OBJECTIVES: To evaluate lung function change
      after eucapnic voluntary hyperventilation (EVH), and to compare IOS indices with
      spirometric maximal expiratory flow measurements. METHODS: Twenty subjects (10
      airway hyperresponsive [AHR+] and 10 normal [AHR--]) underwent IOS and spirometry
      before and for 15 min after 6 min EVH (inhaling 5% CO2, 21% O2, balance N2) at a
      target ventilation of 30 times the baseline value of the forced expiratory volume
      in 1 s (FEV1) at 20 degrees C. AHR+ was defined by a fall in FEV1 of 10% or
      greater from baseline after a provoking challenge. Airway resistance at 5 Hz
      (R5), reactance at 5 Hz, resonant frequency (Fres), area of reactance integrated
      from 5 Hz to Fres (AX), and FEV1 were determined. RESULTS: No baseline spirometry
      values correlated with falls in FEV1. Baseline R5 and AX values correlated with
      peak falls in FEV1 (r= -0.51 and -0.46, respectively; P< 0.05). AHR+ subjects
      demonstrated greater per cent peak falls in FEV1 than did AHR- subjects following
      EVH (30.6 +/- 14.0% versus 7.5 +/- 2.6%, respectively; P<0.05). Changes in R5,
      Fres, reactance and AX were greater for AHR+ subjects than for AHR- subjects and
      correlated with a fall in FEV1 (r= -0.74, -0.70, 0.69 and -0.73, respectively;
      P<0.05). At a designated specificity of 80%, the per cent change in R5 (50% or
      greater) and post-EVH AX (12 cm H2O/L or greater) yielded sensitivities to a 10%
      fall in FEV1 of 90%. CONCLUSION: IOS is an acceptable measure to determine AHR
      and can supplement spirometry in lung function evaluation.

PMID- 16107915
TI  - A systematic review of risk factors associated with near-fatal and fatal asthma.
AB  - BACKGROUND: Asthma mortality and morbidity continue to be a serious global
      problem. Systematic reviews provide an opportunity to review risk factors in
      detail. OBJECTIVE: To review all of the literature for risk factors associated
      with near-fatal asthma (NFA) and fatal asthma (FA). METHODS: A literature search
      from 1960 to January 2004 in MEDLINE and EMBASE was conducted. Studies were
      included based on the following criteria: NFA was defined as an asthma
      exacerbation resulting in respiratory arrest requiring mechanical ventilation or
      a partial pressure of CO2 of at least 45 mmHg or asthma resulting in death (FA);
      the study reported the number of cases (NFA and/or FA) and asthmatic controls;
      there was explicit reporting of risk factors; cases that were adult and pediatric
      in nature; and all study types. Studies that included patients with chronic
      obstructive pulmonary disease were excluded. RESULTS: Four hundred and three
      articles were identified, of which 27 met the inclusion criteria. Increased use
      of medications such as beta-agonists via metered dose inhalers (OR=1.67, 95% CI
      0.99 to 2.84, P=0.057) and nebulizers (OR=2.45, 95% CI 1.52 to 3.93, P=0.0002),
      oral steroids (OR=2.71, 95% CI 1.34 to 5.51, P=0.006) and oral theophylline
      (OR=2.02, 95% CI 1.03 to 3.98, P=0.04) and a history of hospital (OR=2.62, 95% CI
      1.04 to 6.58, P=0.04) and/or intensive care unit (OR=5.14, 95% CI 1.91 to 13.86,
      P=0.001) admissions and mechanical ventilation (OR=6.69, 95% CI 2.80 to 15.97,
      P=0.0001) due to asthma were predictors of NFA and FA. Prior emergency department
      assessment did not confer a greater risk of NFA and FA (OR=1.13, 95% CI 0.43 to
      2.92, P=0.810). The use of inhaled corticosteroids (ICS) measured in a dose
      independent fashion (did the patient take ICS previously; yes or no) inferred
      equivocal risk of NFA and FA (OR=1.31, 95% CI 0.83 to 2.05, P=0.25). However, two
      studies measured the use of ICS in a dose-dependent fashion (ie, measured the
      number of prescriptions filled within the previous six to 12 months). Both
      studies showed a trend toward a protective effect against FA. One study showed
      that the premature cessation of ICS can hasten death. CONCLUSIONS: In the present
      study, risk factors of NFA and FA have been more accurately defined. Clinicians
      should identify patients with these characteristics to reduce their risk of NFA
      and FA. Further research should focus on quantifying the impact of risk factors
      on asthma deaths.

PMID- 16107916
TI  - The current status of autotitrating continuous positive airway pressure systems
      in the management of obstructive sleep apnea.
AB  - BACKGROUND: Autotitrating continuous positive airway pressure (APAP) devices have
      the potential to address some of the disadvantages of titration and treatment
      with conventional continuous positive airway pressure (CPAP). Information on the
      performance of APAP in clinical use is still comparatively limited. OBJECTIVE: To
      assess the status of APAP devices in the management of obstructive sleep apnea
      (OSA) by reviewing evidence of their efficacy, effectiveness and costs. METHODS:
      A systematic search of electronic databases and a review of selected comparative
      studies on the use of APAP in the diagnosis, titration and treatment of OSA was
      undertaken. Cost analysis using data applicable to the management of OSA in
      Edmonton, Alberta was performed. RESULTS: Thirty-three studies met the selection
      criteria: three on the use of APAP in diagnosing OSA; six on APAP for titration;
      14 that considered short-term treatment outcomes; and 10 that addressed longer
      term treatment of OSA. In most studies, patients suffering from cardiac,
      pulmonary and other medical conditions were excluded. Available data suggested
      some potential for the use of APAP in the diagnosis of OSA, but further
      validation is needed. In titration, estimated treatment pressures tended to be
      lower with APAP than with the manual titration of CPAP. Although lower treatment
      pressures were achieved with APAP, there was no significant difference in
      clinical outcome measures between APAP and CPAP. Estimates of costs suggested
      that APAP may provide savings in some scenarios. CONCLUSIONS: APAP shows promise
      in the management of OSA; however, given the exclusion of some categories of
      patients from trials of this technology, caution is still required in its use.

PMID- 16107917
TI  - Hemothorax complicating bronchial artery aneurysm.
AB  - An elderly patient presented with spontaneous hemothorax. Workup identified a
      right-sided bronchial aneurysm as the source, which was successfully embolized.
      Bronchial aneurysms can be managed by interventional techniques, although the
      choice of approach depends upon the clinical and anatomical settings.

PMID- 16107918
TI  - Genomics research: where are the drugs?

PMID- 16107919
TI  - American Society Of Hematology--41st annual meeting. Corporate Friday. 3-7
      December 1999, New Orleans, LA, USA.

PMID- 16107920
TI  - Gene therapy and anticancer therapies I. 3-7 December 1999, New Orleans, LA, USA.

PMID- 16107921
TI  - Breaking news. 3-7 December 1999, New Orleans, LA, USA.

PMID- 16107922
TI  - Gene therapy and anticancer therapies II. 3-7 December 1999, New Orleans, LA,
      USA.

PMID- 16107923
TI  - Biological Therapy of Cancer--fifth symposium. From basic research to clinical
      application. 27-30 October 1999, Munich, Germany.
AB  - This meeting highlighted the exciting progress being made in biological therapies
      for cancer. There are now antibodies licensed for therapy, with cytokines
      available for therapy and growth factors in routine use. Understanding the immune
      system and tumor biology, are vital components of developing novel therapies.
      Cell-mediated immunity is clearly important, not only for vaccine therapies and
      dendritic cell approaches, but also for antibody therapies. The main areas of
      biological therapy covered by the meeting were tumor immunology, vaccine therapy,
      dendritic cell approaches, gene therapy and antibody therapies. Many of these
      biological therapies have now entered phase I trials and appear to be well
      tolerated with minimal side effects. Trial design must be modified, as with these
      therapies standard phase I objectives of establishing the maximum tolerated dose
      (MTD), assessing toxicity and pharmacokinetics must be combined with biological
      'end-points', such as measurement of immune activation or downstream effects. As
      these agents enter phase II efficacy trials, their role will become further
      established. They may provide new alternatives for therapy either alone or in
      combination with current chemotherapeutic agents.

PMID- 16107924
TI  - American Association of Pharmaceutical Scientists--annual meeting and exposition.
      14-18 November 1999, New Orleans, LA, USA.

PMID- 16107925
TI  - Drug efflux pumps: challenges and opportunities. 14-18 November 1999, New
      Orleans, LA, USA.
AB  - A symposium entitled 'Drug efflux pumps: challenges and opportunities' addressed
      the detection and functional characterization of drug efflux pumps, their
      influence on the cytochrome P450 (CYP450) system and their role in blood-brain
      barrier (BBB) permeability. Drug efflux pumps utilize ATP as the energy source in
      exporting solutes, and belong to the family of ATP-binding cassette transporters
      (ABC transporters). P-glycoprotein (Pgp) and multidrug resistance-associated
      protein (MRP) are members of this family of transporters. These transporters are
      overexpressed in cancer cells leading to decreased drug accumulation and hence
      drug resistance. Another causative factor for drug resistance is increased
      elimination mechanisms, metabolism by CYP450 enzymes being the most important.
      The multidrug resistance gene (mdr) is a key determinant in the expression of
      CYP3A enzymes, the most predominant subclass of CYP450. New techniques are being
      developed to identify and characterize drug efflux pumps, the latest being gamma
      scintigraphy and hypertonic saline (HTS). Efflux pumps play a major role in
      restricting the drug transport across the BBB. Currently, structural domains that
      are responsible for the functional activity of the efflux proteins are being
      investigated to design better inhibitors for drug efflux pumps.

PMID- 16107926
TI  - Plenary session. 14-18 November 1999, New Orleans, LA, USA.

PMID- 16107927
TI  - New medicines from heterocycles--Royal Society of Chemistry meeting. 11 November
      1999, London, UK.

PMID- 16107928
TI  - Multiple risk factors in cardiovascular disease--fifth international symposium.
      28-31 October 1999, Venice, Italy.
AB  - This meeting primarily dealt with the assessment of global risk for the
      development of cardiovascular disease. There was also a discussion of the ongoing
      trials with hypolipidemic drugs, especially statins. Particular emphasis was
      given to the management of dyslipidemia observed in diabetic patients.

PMID- 16107929
TI  - American College of Rheumatology--63rd annual meeting. 13-17 November 1999,
      Boston, MA, USA.
AB  - The 63rd National Scientific Meeting of the American College of Rheumatology was
      quite general in scope, with clinical and animal model studies forming the basis
      for this report. Arthritis-suppressive medications were further analyzed as to
      morbidity and effect on disease progression. Biological therapy was an important
      topic. Intervention for gastroprotection, osteoarthritis, spondyloarthropathy,
      lupus, osteoporosis and antiphospholipid antibodies, was especially explored.

PMID- 16107930
TI  - North American Society for the Study of Obesity--annual meeting. Emerging
      perspectives on obesity. 14-18 November 1999, Charleston, SC, USA.
AB  - This meeting focused on the latest research and clinical developments in the
      field of obesity. Record high attendance emphasized the recognition of obesity as
      an emerging and exciting area of study, both from the basic science aspects as
      well as from a clinical standpoint. While presentations at the meeting emphasized
      the importance of retaining our current public health message of low-fat diets
      and exercise for obesity prevention and management, several novel approaches
      (both behavioral and pharmaceutical) were also presented. In animal models, the
      presentation of data on a novel obesity-related gene, beacon, was one of the
      highlights.

PMID- 16107931
TI  - Molecular targets and cancer therapeutics: discovery, development & clinical
      validation--AACR-NCI-EORTC international conference.
AB  - This meeting covered a wide area of cancer research including the latest
      developments in drug discovery, new targets and translational research into the
      clinic. A flavor of this meeting is reported here.

PMID- 16107932
TI  - PDE inhibitors--Second William Harvey Research Conference. Drugs with an
      expanding range of therapeutic uses. 1-3 December 1999, Nice, France.
AB  - This meeting underscored advances in the exploitation of cyclic nucleotide
      phosphodiesterases (PDEs) as drug targets. One highlight of the meeting was the
      disclosure of a new PDE isozyme, bringing to 11 the total number of genetically
      distinct isozyme families thus far identified. Also reported was the phenotypic
      characterization of a PDE4D murine genetic knockout. With respect to drug
      discovery and development, the most encouraging information presented centered on
      advances in targeting PDE4 with therapeutically useful inhibitors. Historically,
      the therapeutic utility of isozyme-selective PDE4 inhibitors has been limited by
      class-associated side effects, namely nausea and dyspepsia. New PDE4 inhibitors
      are being designed with the specific intent of improving upon the therapeutic
      ratio of first-generation agents. The profiles of two second-generation PDE4
      inhibitors, SB-207499 (Ariflo; Smithkline Beecham plc) and PD-189659, were
      presented. SB-207499 demonstrated marked efficacy in phase II clinical trials in
      patients with moderate-to-severe chronic obstructive pulmonary disease (COPD), a
      disease of very high unmet medical need. PD-189659 has yet to enter clinical
      trials, but its preclinical profile indicates that this agent can produce
      substantial anti-inflammatory effects without producing class-associated side
      effects in animal models. A number of presentations were also given on the
      utility of PDE5 inhibitors in the treatment of male erectile dysfunction (MED).
      The widespread use of Viagra (sildenafil; Pfizer Inc) over the last year has
      reinforced the perception that PDE5 inhibitors are safe and effective agents for
      the treatment of MED. The overall tenor of the meeting was distinctly upbeat,
      with most participants believing that PDE isozymes are becoming ever more
      accessible as targets for drug discovery in a variety of therapeutic areas.

PMID- 16107933
TI  - BPS epilepsy joint symposium. 18 November 1999, London, UK.
AB  - This symposium, jointly organized by the British Pharmacological Society, the
      Pharmaceutical Sciences Group of the Royal Pharmaceutical Society and the
      National Society for Epilepsy, provided comprehensive information on anti
      epileptic therapy and drug development issues. The spectrum of medical imaging
      techniques was evaluated for application in patient classification and diagnosis,
      therapeutic or surgical options, and for studying sites and mechanisms of drug
      action. The value of established therapeutics, as opposed to recent new drug
      interactions and therapeutics awaiting registration, were discussed in view of
      their clinical pharmacology, therapeutic use and drug-drug interaction
      properties. There were discussions on clinical drug testing problems in relation
      to trial design, and drug screening strategies from the perspective of perceived
      unmet clinical needs, such as refractory epilepsy and epileptogenesis. New
      developments, especially in the field of glutamate modulation, were reviewed for
      anti-epileptic drug potential. The conclusion was that in spite of progress,
      rational drug development of anti-epileptic drugs is still far away. Possible
      reasons for this could be that during drug screening, the focus is on drug
      properties in isolated rather than integrated neuronal circuits. In addition,
      there is a poor translation of drug effects in models for seizures and
      convulsions compared with epilepsy and epileptogenesis in man, and also the
      obstacle of rigidity in drug registration trials. It was a very valuable meeting
      for those who wanted to be informed about the frontiers and challenges in the
      development of anti-epileptic drugs.

PMID- 16107934
TI  - Japanese Society for Retinoid Research--tenth symposium. 17-19 November 1999,
      Tokyo, Japan.

PMID- 16107935
TI  - Predictive toxicology in drug discovery--second international conference. New
      technologies for predicting toxic responses at an early stage. 10-11 November
      1999, New Orleans, LA, USA.
AB  - This meeting focused on the problems facing the pharmaceutical industry, given
      the need for faster and higher throughput toxicity testing, and how emerging
      technologies are being applied to address this need. Inevitably, the emphasis was
      on in vitro approaches, in particular, genomics-based technology such as
      transcript profiling, but due attention was paid to the necessity of relating in
      vitro-derived data to toxic endpoints in vivo. A number of technology-providing
      companies were given the opportunity to draw attention to their proprietary
      systems and explain how they might be applied to drug safety assessment. Finally,
      a session was devoted to a discussion of available 'in silico' systems and how
      these are being developed and refined as the need for computer-based screening
      increases.

PMID- 16107936
TI  - IUPHAR Southeast Asian-Western Pacific Region--eighth Meeting. Pharmacology in
      the Next Millennium. 1-5 November 1999, Taipei, Taiwan.
AB  - This conference focused on some areas of particular interest to pharmacologists
      in the Asia-Pacific region, including prostanoids, drug metabolism and drugs from
      traditional Chinese herbs. Areas covered in the prostanoid sessions included
      reviews of the development of selective COX-2 inhibitors, the use of knockout
      mice to study the role of prostanoid receptors in various disease states, the
      interactions of G-protein-coupled receptor pathways, and the effects of
      prostanoid mimetics on autonomic neurons. Sessions on drug metabolism reviewed
      the use of transgenic mouse models for toxicological screening of new drugs, the
      use of a combination of probe drugs given together to identify the activity of a
      range of drug metabolizing enzymes in vivo, and the interaction of drug
      metabolizing enzymes and nitric oxide. In the presentations on herbal medicines,
      there were discussions about the regulatory status and the problems involved in
      conducting clinical trials with these preparations. There were a number of
      seminars on details of the basic or clinical pharmacology of some active
      principles derived from herbs, thus recognizing the intense effort by local
      pharmacologists to improve the scientific study of this important resource.

PMID- 16107937
TI  - AstraZeneca plc's first pharmaceuticals R&D presentation. 6 December 1999,
      London, UK.

PMID- 16107938
TI  - Discovery of endothelin receptor antagonists from natural products.

PMID- 16107939
TI  - Hyaluronan--a review of the recent patent literature.
AB  - A review of patent literature surrounding the use of hyaluronan (HA) and its
      derivatives, or agents capable of modulating endogenous levels, is presented.
      Indications are many and varied and include arthritis, abnormal wound healing,
      neoplasia, prevention of surgical adhesions and dermatological disorders. In many
      cases, it is the physicochemical and biological properties of HA itself that have
      been exploited. For example, HA and/or its derivatives have been suggested as a
      synovial fluid replacement, a vehicle for topical application of drugs, a matrix
      for sustained drug release and a putative drug delivery system (targeting HA
      receptors at sites of pathology). In each of these examples, the lack of toxicity
      of HA and its biocompatability are important considerations.

PMID- 16107940
TI  - Alkaloid lead molecules for cholinergic drug development.

PMID- 16107941
TI  - ONO-5046 (Ono Pharmaceutical).
AB  - ONO-5046 (sivelestat) is a competitive inhibitor of human neutrophil elastase
      from Ono Pharmaceutical, which is awaiting FDA approval for the treatment of
      pulmonary fibrosis and idiopathic interstitial pneumonia [349488]. An NDA was
      filed in Japan in September 1998 [299667]. It is in phase II trials for the
      treatment of acute circulatory failure [171678]. It is also being investigated as
      a potential treatment of arthritis [230100]. In animal models of asthma,
      sivelestat decreased the level of hemorrhage and protein extravasation into the
      bronchoalveolar lavage fluid after the administration of a 40 mg/kg injection of
      phorbol myristate acetate [188186]. The compound also inhibited the growth of
      human lung cancer cell lines in SCID mice [269736]. Sivelestat inhibits gastric
      lesion formation in rats subjected to water immersion restraint stress. Low oral
      bioavailability in vivo is due to extensive hepatic first-pass metabolism.
      Endotoxin-induced lung injury in rabbits was attenuated by pretreatment with
      sivelestat [276401]. In 1996, analysts at Yamaichi estimated sivelestat would be
      launched in Japan between 1998/9 and peak annual sales would be less than 5
      billion yen [216018].

PMID- 16107942
TI  - PD-140248 (Parke-Davis & Co).
AB  - PD-140248 is an isomerase inhibitor and topoisomerase II inhibitor under
      development by Parke-Davis and Co as a potential treatment for bacterial
      infection. Although no details of active development have been published in the
      scientific literature since 1996, in September 1999, the company confirmed that
      PD-140248 is still in active development [338530]. The compound is one of two new
      pyrrolidinyl naphthyridines (the other compound being PD-131628) with a broad
      spectrum of antibacterial activity, including activity against quinolone
      resistant bacteria. PD-140248 demonstrates strong in vitro activity, particularly
      against Gram-positive bacteria, such as quinolone-susceptible Staphylococcus
      aureus (S aureus), Staphylococcus epidermidis (S epidermidis), Staphylococcus
      haemolyticus (S haemolyticus), methicillin- and ciprofloxacin-resistant S aureus,
      Streptococcus species, Streptococcus pneumoniae (S pneumoniae) and Enterococcus
      faecalis (E faecalis). An MIC90 value of 0.015 microg/ml was obtained against
      Haemophilus influenzae (H influenzae) and Moraxella catarrhalis [160129]. The
      (3R,1S) enantiomer, PD-140248, demonstrated a 1- to 10-fold enhanced activity
      against Gram-positive and Gram-negative organisms in vitro and in vivo compared
      to its stereoisomers, and has thus been targeted for further preclinical studies
      [133377].

PMID- 16107943
TI  - Belaperidone (Knoll AG).
AB  - Knoll is developing belaperidone, an antipsychotic agent, as a potential new
      treatment for schizophrenia. Phase II trials have commenced in Germany
      [200089,333710]. The compound is regarded as an atypical antipsychotic, similar
      in profile to clozapine, with potential to help patients whose illness has become
      difficult or impossible to treat. In rats, cumulative doses of belaperidone
      (0.128 to 32.768 mg/kg) reversed inhibition of the firing rate in the substantia
      nigra dopaminergic neurons induced by iv quinpirole. The ED50 value for the
      inhibition was 1.66 mg/kg, which is twice as potent as clozapine and 40-fold less
      potent than haloperidol. The drug did not produce catalepsy [346021]. In addition
      to possessing high affinity for 5-HT2 receptors (Ki = 3.3 nM), belaperidone
      selectively antagonizes the dopamine D4 (Ki = 3.1 nM) receptor, in preference to
      the D2 (Ki = 105 nM) subtype [247874]. It also has very low muscarinic affinity
      (Ki > 200 nM) [289024], [333710].

PMID- 16107944
TI  - CD4 lymphocyte percentage versus absolute CD4 lymphocyte count in predicting HIV
      disease progression: an old debate revisited.

PMID- 16107945
TI  - Posttreatment chronic Lyme disease--what it is not.

PMID- 16107946
TI  - CD4 lymphocyte percentage predicts disease progression in HIV-infected patients
      initiating highly active antiretroviral therapy with CD4 lymphocyte counts >350
      lymphocytes/mm3.
AB  - BACKGROUND: The optimal timing of highly active antiretroviral therapy (HAART) in
      human immunodeficiency virus (HIV)-infected patients with > or = 200 absolute CD4
      lymphocytes/mm3 is unknown. CD4 lymphocyte percentage could add prognostic
      information. METHODS: Persons who initiated HAART between 1 January 1998 and 1
      January 2003, received > or = 30 days of therapy, and had baseline CD4 lymphocyte
      data available were included in the study. The log-rank test for time to event
      and Cox proportional hazards models were used to determine predictors of a new
      acquired immunodeficiency syndrome-defining illness or death. RESULTS: A total of
      788 patients met the inclusion criteria. At baseline, subjects had a median of
      225 CD4 lymphocytes/mm3 and 17% CD4 lymphocytes. Subjects with < 17% CD4
      lymphocytes had earlier disease progression, compared with subjects with > or =
      17%, both in the entire cohort (P<.0001) and of those subjects with > 350
      absolute CD4 lymphocytes/mm3 at baseline (P=.03). CD4 lymphocyte percentage < 17%
      was the strongest predictor of disease progression among subjects in this latter
      group (hazard ratio, 3.57; P=.045). CONCLUSIONS: In this cohort, CD4 lymphocyte
      percentage predicted disease progression in HIV-infected subjects who initiated
      therapy with > 350 CD4 lymphocytes/mm3. This information may help identify
      persons who will derive the greatest benefit from initiation of HAART.

PMID- 16107947
TI  - Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe:
      implications for clinical management.
AB  - BACKGROUND: Infection with drug-resistant human immunodeficiency virus type 1
      (HIV-1) can impair the response to combination therapy. Widespread transmission
      of drug-resistant variants has the disturbing potential of limiting future
      therapy options and affecting the efficacy of postexposure prophylaxis. METHODS:
      We determined the baseline rate of drug resistance in 2208 therapy-naive patients
      recently and chronically infected with HIV-1 from 19 European countries during
      1996-2002. RESULTS: In Europe, 1 of 10 antiretroviral-naive patients carried
      viruses with > or = 1 drug-resistance mutation. Recently infected patients
      harbored resistant variants more often than did chronically infected patients
      (13.5% vs. 8.7%; P=.006). Non-B viruses (30%) less frequently carried resistance
      mutations than did subtype B viruses (4.8% vs. 12.9%; P<.01). Baseline resistance
      increased over time in newly diagnosed cases of non-B infection: from 2.0% (1/49)
      in 1996-1998 to 8.2% (16/194) in 2000-2001. CONCLUSIONS: Drug-resistant variants
      are frequently present in both recently and chronically infected therapy-naive
      patients. Drug-resistant variants are most commonly seen in patients infected
      with subtype B virus, probably because of longer exposure of these viruses to
      drugs. However, an increase in baseline resistance in non-B viruses is observed.
      These data argue for testing all drug-naive patients and are of relevance when
      guidelines for management of postexposure prophylaxis and first-line therapy are
      updated.

PMID- 16107948
TI  - Estimating HIV-1 drug resistance in antiretroviral-treated individuals in the
      United Kingdom.
AB  - Good estimates of the prevalence of human immunodeficiency virus drug resistance
      are important for assessing requirements for new drug classes and modeling the
      spread of resistance. However, little consensus exists on optimal methodologies
      to generate such data. To compare methodologies, we used the national data set of
      resistance tests from >4000 patients in the United Kingdom performed between 1998
      and 2002. When single-time-point analysis (method 1) was used, the proportion of
      tests with any form of resistance was approximately 80%, with little time trend.
      When a cumulative model of resistance (method 2) was used and placed in the
      context of all treated patients, the prevalence of any resistance increased by
      year, reaching 17% of treated patients in 2002. Method 2 also nearly doubles
      estimates of numbers of individuals infected with multiclass drug-resistant
      virus. Our results identify an urgent need for new drugs within existing classes
      and new classes of antiretroviral therapy.

PMID- 16107949
TI  - HIV-1 virologic and immunologic progression and initiation of antiretroviral
      therapy among HIV-1-infected subjects in a trial of the efficacy of recombinant
      glycoprotein 120 vaccine.
AB  - The first trial of the efficacy of a human immunodeficiency virus (HIV)-1 vaccine
      was conducted in North America and The Netherlands between 1998 and 2003. This
      multicenter, randomized, placebo-controlled trial of a recombinant glycoprotein
      120 vaccine included 5403 initially HIV-negative volunteers who were monitored
      for 3 years. The 368 subjects who acquired HIV-1 infection were monitored for 2
      years by use of the following postinfection end points: plasma HIV-1 RNA level
      (viral load), CD4+ lymphocyte count, initiation of antiretroviral therapy (ART),
      and HIV-1-related clinical outcomes. This article reports the study results that
      pertain to the effect of vaccination on the postinfection end points. The time
      until initiation of ART and the time until virologic failure or initiation of ART
      were similar in the vaccine arm and the placebo arm. The pre-ART viral load and
      CD4+ lymphocyte count trajectories were also comparable between the groups.
      Evidently, the vaccine did not affect HIV-1 disease progression.

PMID- 16107950
TI  - Effects of HIV-1 serostatus, HIV-1 RNA concentration, and CD4 cell count on the
      incidence of malaria infection in a cohort of adults in rural Malawi.
AB  - BACKGROUND: To assess the effects of human immunodeficiency virus (HIV) infection
      on susceptibility to malaria, we compared the incidence rates of malaria by HIV
      type 1 (HIV-1) serostatus, baseline blood HIV-1 RNA concentration, and baseline
      CD4 cell count, over the course of a malaria season. METHODS: We followed a
      cohort of 349 adults in Malawi. For the 224 HIV-1-seropositive adults (64% of the
      cohort), we measured HIV-1 RNA concentration (n=187) and CD4 cell count (n=184)
      at baseline. Parasitemia was defined as presence of asexual parasites on a thick
      film of blood and was treated with sulfadoxine/pyrimethamine (SP), in accordance
      with national policy. Hazard ratios (HRs) of parasitemia were estimated using Cox
      regression. Demographics were adjusted for. RESULTS: HIV-1 seropositivity was
      associated with parasitemia (adjusted HR, 1.8 [95% confidence interval {CI}, 1.2
      2.7] for a first parasitemia episode; adjusted HR, 2.5 [95% CI, 1.5-4.2] for a
      second parasitemia episode [> 14 days after the first episode]; adjusted HR, 1.9
      [95% CI, 1.4-2.6] for parasitemia overall). Treatment failure (parasitemia < or =
      14 days after SP treatment) did not differ by HIV-1 serostatus (risk ratio, 1.3
      [95% CI, 0.5-3.2]). HIV-1 RNA concentrations and CD4 cell counts were moderately
      but inconsistently associated with parasitemia. A high parasite density with
      fever was associated with HIV-1 seropositivity and low CD4 cell count.
      CONCLUSION: HIV-infected adults in malaria-endemic areas are at increased risk
      for malaria. Where possible, additional malaria prevention efforts should be
      targeted at this population.

PMID- 16107951
TI  - Influence of hepatitis C virus infection on HIV-1 disease progression and
      response to highly active antiretroviral therapy.
AB  - OBJECTIVE: To assess hepatitis C virus (HCV) antibody prevalence in the EuroSIDA
      cohort, along with survival, human immunodeficiency virus (HIV)-1 disease
      progression, virologic response (plasma HIV-1 RNA load of < 500 copies/mL), and
      CD4 cell count recovery by HCV serostatus in patients initiating highly active
      antiretroviral therapy (HAART). RESULTS: HCV serostatus at or before enrollment
      was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive
      and seronegative, respectively. No association between an increased incidence of
      acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus
      was seen after adjustment for other prognostic risk factors known at baseline
      (adjusted incidence rate ratio [IRR], 0.97 [95% confidence interval {CI}, 0.81
      1.16]). However, there was a large increase in the incidence of liver disease
      related deaths in HCV-seropositive patients in adjusted models (IRR, 11.71 [95%
      CI, 6.42-21.34]). Among 2260 patients of known HCV serostatus initiating HAART,
      after adjustment, there was no significant difference between HCV-seropositive
      and -seronegative patients with respect to virologic response (relative hazard
      [RH], 1.13 [95% CI, 0.84-1.51]) and immunologic response, whether measured as a >
      or = 50% increase (RH, 0.94 [95% CI, 0.77-1.16]) or a > or = 50 cells/microL
      increase (RH, 0.92 [95% CI, 0.77-1.11]) in CD4 cell count after HAART initiation.
      CONCLUSIONS: HCV serostatus did not affect the risk of HIV-1 disease progression,
      but the risk of liver disease-related deaths was markedly increased in HCV
      seropositive patients. The overall virologic and immunologic responses to HAART
      were not affected by HCV serostatus.

PMID- 16107952
TI  - Attenuation of HIV-1 infection by other microbial agents.
AB  - Although potentiation of human immunodeficiency virus (HIV) type 1 (HIV-1)
      infection has been known to occur in coinfection with a variety of pathogens and
      types of vaccination, there are emerging data on specific infectious agents that
      may attenuate HIV-1 infection. New literature suggests that certain pathogens are
      capable of inhibiting HIV-1 replication. These include GB virus C, measles virus,
      Orientia tsutsugamushi, and human T lymphotropic virus types 1 and 2. In
      addition, there are conflicting data on the effects of Mycobacterium tuberculosis
      on the replication of HIV-1, with some suggesting that this organism may inhibit
      HIV-1 replication. Also remaining controversial are the possible protective
      effects of HIV type 2 against HIV-1 infection. In this review, we summarize and
      critically discuss the body of emerging literature concerning infections that may
      have the ability to attenuate HIV-1 infection.

PMID- 16107953
TI  - A case-control study to examine HLA haplotype associations in patients with
      posttreatment chronic Lyme disease.
AB  - In a comparison of 95 patients with systemic symptoms that persisted after
      antibiotic treatment for acute Lyme disease (posttreatment chronic Lyme disease)
      and 104 control subjects without such symptoms after antibiotic treatment, we
      sought associations between human leukocyte antigen class II (DRB1 and DQB1)
      markers and posttreatment chronic Lyme disease. No strong association between
      posttreatment chronic Lyme disease and any class II allele or genotype was found.

PMID- 16107954
TI  - Vascular dysfunction and ischemic destruction of tissue in Streptococcus pyogenes
      infection: the role of streptolysin O-induced platelet/neutrophil complexes.
AB  - Rapid tissue destruction in group A streptococcal (GAS) necrotizing
      fasciitis/myonecrosis often necessitates extensive debridement to ensure
      survival. The mechanisms responsible for this fulminant process remain unknown;
      we hypothesized that toxin-induced ischemia contributes to necrosis. In a rat
      model, Doppler flowmetry was used to measure local blood flow at the site of the
      intramuscular injection of exotoxins from an invasive M-type 1 GAS, which caused
      a rapid, dose-dependent decrease in perfusion that was irreversible at the
      highest toxin concentration tested. Videomicroscopic results revealed that blood
      flow was impeded by occlusive intravascular cellular aggregates. Flow-cytometric
      results confirmed that GAS toxins induced the coaggregation of platelets and
      neutrophils, that this activity was attributable to streptolysin O, and that
      platelet/neutrophil complex formation was largely mediated by platelet P-selectin
      (CD62P). Strategies that target platelet adherence molecules may prevent vascular
      occlusion, maintain tissue viability, and reduce the need for amputation in
      necrotizing GAS infections.

PMID- 16107955
TI  - Evidence of an intracellular reservoir in the nasal mucosa of patients with
      recurrent Staphylococcus aureus rhinosinusitis.
AB  - Severe infections due to Staphylococcus aureus require prolonged therapy for
      cure, and relapse may occur even years after the first episode. Persistence of S.
      aureus may be explained, in part, by nasal carriage of S. aureus, which occurs in
      a large percentage of healthy humans and represents a major source of systemic
      infection. However, the persistence of internalized S. aureus within mucosal
      cells has not been evaluated in humans. Here, we provide the first in vivo
      evidence of intracellular reservoirs of S. aureus in humans, which were assessed
      in endonasal mucosa specimens from patients suffering from recurrent S. aureus
      rhinosinusitis due to unique, patient-specific bacterial clonotypes. Heavily
      infected foci of intracellular bacteria located in nasal epithelium, glandular,
      and myofibroblastic cells were revealed by inverted confocal laser scan
      fluorescence and electron microscopic examination of posttherapy intranasal
      biopsy specimens from symptom-free patients undergoing surgery on the sinuses.
      Intracellular residence may provide a sanctuary for pathogenic bacteria by
      protecting them from host defense mechanisms and antibiotic treatment during
      acute, recurrent S. aureus rhinosinusitis.

PMID- 16107956
TI  - The respiratory pathogen Moraxella catarrhalis adheres to epithelial cells by
      interacting with fibronectin through ubiquitous surface proteins A1 and A2.
AB  - Moraxella catarrhalis ubiquitous surface protein (Usp) A1 has been reported to
      bind fibronectin and is involved in adherence. In this study, using M.
      catarrhalis mutants derived from clinical isolates, we show that both UspA1 and
      UspA2 bind fibronectin. Recombinant truncated UspA1/A2 proteins, together with
      smaller fragments spanning the entire molecule, were tested for binding to
      fibronectin. Both UspA1 and UspA2 bound fibronectin, and the fibronectin-binding
      domains were located within UspA1(299-452) and UspA2(165-318). These 2 truncated
      proteins inhibited binding of M. catarrhalis to Chang conjunctival epithelial
      cells to an extent similar to that by anti-human fibronectin antibodies. Our
      observations show that both UspA1 and UspA2 are involved in adherence to
      epithelial cells via cell-associated fibronectin. The biologically active sites
      within UspA1(299-452) and UspA2(165-318) have therefore been suggested to be
      potential candidates to be included in a future vaccine against M. catarrhalis.

PMID- 16107957
TI  - Suppressor alphabeta T lymphocytes control innate resistance to endotoxic shock.
AB  - A considerable amount of research has focused on elucidating the mechanisms by
      which cytokines synthesized by cells of the innate immune system participate in
      the life-threatening multiple-organ failure of endotoxic shock. We show here that
      alphabeta T cells, which are archetypes of the adaptive cellular immune response,
      suppress the proinflammatory cascade triggered during the early stages of
      lipopolysaccharide (LPS)-induced endotoxemia. The absence of alphabeta T cells
      led to the fulminant death of LPS-challenged mice, coinciding with a massive
      release of the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and
      interferon (IFN)-gamma and a marked reduction in the synthesis of the
      immunosuppressive cytokine transforming growth factor (TGF)-beta. Cytotoxic T
      lymphocyte antigen (CTLA)-positive alphabeta T cells emerging shortly after LPS
      challenge appear to control TGF-beta synthesis. The neutralization of either TGF
      beta or CTLA4 resulted in similar increases in IFN-gamma and TNF-alpha serum
      concentrations in LPS-challenged mice. These observations suggest that suppressor
      alphabeta T lymphocytes protect against the proinflammatory cascade unleashed
      during the innate stages of endotoxemia.

PMID- 16107958
TI  - A soluble receptor decoy protects rats against anthrax lethal toxin challenge.
AB  - Successful postexposure treatment for inhalation anthrax is thought to include
      neutralization of anthrax toxin. The soluble anthrax toxin receptor/tumor
      endothelial marker 8 and capillary morphogenesis protein 2 (sATR/TEM8 and sCMG2,
      respectively) receptor decoys bind to anthrax toxin protective antigen (PA) and
      compete with cellular receptors for binding. Here, we show that, in a tissue
      culture model of intoxication, sCMG2 is a 11.4-fold more potent antitoxin than
      sATR/TEM8 and that this increased activity corresponds to an approximately 1000
      fold higher PA-binding affinity. Stoichiometric concentrations of sCMG2 protect
      rats against lethal toxin challenge, making sCMG2 one of the most effective
      anthrax antitoxins described to date.

PMID- 16107959
TI  - Detection of severe human metapneumovirus infection by real-time polymerase chain
      reaction and histopathological assessment.
AB  - BACKGROUND: Infections with common respiratory tract viruses can cause high
      mortality, especially in immunocompromised hosts, but the impact of human
      metapneumovirus (hMPV) in this setting was previously unknown. METHODS: We
      evaluated consecutive bronchoalveolar lavage and bronchial wash fluid samples
      from 688 patients--72% were immunocompromised and were predominantly lung
      transplant recipients--for hMPV by use of quantitative real-time polymerase chain
      reaction (PCR), and positive results were correlated with clinical outcome and
      results of viral cultures, in situ hybridization, and lung histopathological
      assessment. RESULTS: Six cases of hMPV infection were identified, and they had a
      similar frequency and occurred in a similar age range as other paramyxoviral
      infections. Four of 6 infections occurred in immunocompromised patients.
      Infection was confirmed by in situ hybridization for the viral nucleocapsid gene.
      Histopathological assessment of lung tissue samples showed acute and organizing
      injury, and smudge cell formation was distinct from findings in infections with
      other paramyxoviruses. Each patient with high titers of hMPV exhibited a
      complicated clinical course requiring prolonged hospitalization. CONCLUSIONS: Our
      results provide in situ evidence of hMPV infection in humans and suggest that
      hMPV is a cause of clinically severe lower respiratory tract infection that can
      be detected during bronchoscopy by use of real-time PCR and routine
      histopathological assessment.

PMID- 16107960
TI  - A prospective study comparing human metapneumovirus with other respiratory
      viruses in adults with hematologic malignancies and respiratory tract infections.
AB  - Human metapneumovirus (hMPV) is a recently described paramyxovirus associated
      with upper and lower respiratory-tract infection (URI and LRI, respectively). We
      conducted a prospective study of URI and LRI in adults with hematologic
      malignancies during a 4-year period. We retrospectively tested samples by reverse
      transcription polymerase chain reaction for hMPV and analyzed clinical data.
      Twenty-two (9%) of 251 episodes of respiratory infection tested positive for
      hMPV. Sixteen (73%) of the illnesses occurred in hematopoietic stem-cell
      transplant recipients. Nine patients with hMPV developed LRI; 3 of these patients
      died. hMPV is a common cause of respiratory infections in adults with hematologic
      malignancies, with associated morbidity and mortality.

PMID- 16107961
TI  - Clinical responses to smallpox vaccine in vaccinia-naive and previously
      vaccinated populations: undiluted and diluted Lancy-Vaxina vaccine in a single
      blind, randomized, prospective trial.
AB  - We conducted a single-blind, randomized trial of 2 dilutions (1:1 or 1:10) of
      Lancy-Vaxina vaccine (Berna Biotech) in vaccinia-naive persons (n=36) and persons
      previously vaccinated >25 years ago (n=76). All vaccinees responded successfully
      to the vaccination. There were no significant differences in the size of the skin
      lesions, the number of adverse events, the amount of viral shedding, or the level
      of antibody responses between the undiluted (n=56) and diluted (n = 56) vaccine
      groups. Compared with vaccinia-naive persons, previously vaccinated persons
      exhibited significantly smaller and more rapidly evolving skin lesions and fewer
      adverse events. Previously vaccinated persons had significantly higher
      neutralizing antibody levels before the administration of the study vaccine than
      vaccinia-naive persons, and viral shedding from lesions in previously vaccinated
      persons was lower and diminished more rapidly than from lesions in vaccinia-naive
      persons.

PMID- 16107962
TI  - Influence of the combined ABO, FUT2, and FUT3 polymorphism on susceptibility to
      Norwalk virus attachment.
AB  - The binding of Norwalk virus (NV) recombinant capsids was tested in a panel of
      saliva samples collected from 96 donors with different ABO, secretor, and Lewis
      phenotypes. As previously reported, binding occurred specifically to saliva from
      secretors, regardless of their Lewis phenotype status. Blood group B saliva was
      poorly recognized, whereas binding to blood group O saliva was higher and binding
      to blood group A saliva was highest. Transfection of either blood group A or B
      enzyme into H epitope-expressing cells showed that masking of H epitopes by the A
      and B antigens blocked the attachment of NV capsids. The high level of binding to
      blood group A secretor saliva could be explained by an optimal H type 1 ligand
      density, which was lower than that in blood group O saliva and much higher than
      that in blood group B saliva. Indeed, despite a higher ligand density, saliva
      from homozygotes with 2 functional FUT2 alleles was less strongly recognized than
      saliva from heterozygotes with 1 functional and 1 inactivated FUT2 allele.
      Partial fucosidase treatment of duodenal tissue sections and binding to a
      synthetic probe with varying densities of H type 1 trisaccharide indicated that
      optimal attachment occurred at medium ligand density.

PMID- 16107963
TI  - Hepatitis C virus genotype 1a NS5A pretreatment sequence variation and viral
      kinetics in African American and white patients.
AB  - In hepatitis C virus (HCV) infection, race is a determinant of treatment response
      and interferon (IFN) effectiveness. Here, we investigated whether there were
      differences in the pretreatment viral strains between African American patients
      and white patients and whether these differences correlated with viral kinetics.
      IFN effectiveness was calculated using a viral kinetic model. The HCV NS5A region
      from 21 treated patients with HCV genotype 1a was sequenced and analyzed. White
      patients displayed more mutations in the V3 region (mean+/-SD, 4.5+/-1.4 vs.
      2.9+/-1.6; P=.016), and treatment responders tended to have more mutations in
      this region than did nonresponders. There was a significant positive correlation
      between IFN effectiveness and the number of mutations in the V3 region (P=.03).
      There was no clustering of strains by race, treatment response, or IFN
      effectiveness in phylogenetic analyses. The results of this study, in conjunction
      with those of a previous study illustrating the impaired IFN effectiveness in
      African Americans, suggest a role for host-related factors.

PMID- 16107964
TI  - Reemergence of hepatitis C virus after 8.5 years in a patient with
      hypogammaglobulinemia: evidence for an occult viral reservoir.
AB  - The question of whether viruses persist after apparent clearance of infection
      remains unanswered. Here, we describe a patient with hypogammaglobulinemia whose
      acute hepatitis C virus (HCV) infection appeared to resolve after receipt of
      interferon therapy, relapse immediately, and then clear spontaneously--only to
      relapse after receipt of corticosteroid therapy, and clear again, 8.5 years
      later. Sequencing indicated that the viruses detected during each relapse were
      virtually identical, with the hypervariable region 1 of E2 appearing to be
      monoclonal, which is typical of patients with hypogammaglobulinemia.
      Nonstructural 5A sequences exhibited quasispecies diversity initially but, after
      8.5 years, had become monoclonal. The prolonged period of negativity for HCV RNA
      followed by relapse suggests that HCV may persist in apparent sustained viral
      responders.

PMID- 16107965
TI  - CD8+ T cell depletion amplifies hepatitis C virus replication in peripheral blood
      mononuclear cells.
AB  - We investigated the ability of CD8+ T cells to inhibit hepatitis C virus (HCV)
      replication in peripheral blood mononuclear cells (PBMCs). PBMCs isolated from 11
      of 20 HCV-infected subjects had no detectable HCV RNA. Removal of CD8+ T cells
      from these PBMCs resulted in detection of HCV RNA, and depletion of CD8+ T cells
      from PBMCs that had detectable HCV RNA amplified HCV replication. Reconstitution
      of CD8- PBMCs with autologous CD8+ T cells led to inhibition of HCV replication.
      Interferon-gamma produced by CD8+ T cells was partially responsible for CD8+ T
      cell-mediated noncytotoxic anti-HCV activity in PBMCs. This noncytotoxic anti-HCV
      activity was confirmed in HCV replicon cells. Supernatants from CD8+ T cell
      cultures inhibited HCV RNA expression in the replicon cells. These findings may
      have important implications for the immunopathogenesis of HCV in both immune and
      hepatic cells and are relevant to the development of host innate immunity-based
      anti-HCV interventions.

PMID- 16107966
TI  - Acyclovir sensitivity of sequential herpes simplex virus type 2 isolates from the
      genital mucosa of immunocompetent women.
AB  - BACKGROUND: Despite widespread use of acyclovir, infection with acyclovir
      resistant herpes simplex virus type 2 (HSV-2) remains uncommon. To understand the
      frequency and clinical significance of acyclovir-resistant isolates, we evaluated
      the in vitro acyclovir sensitivities of sequential isolates from 34
      immunocompetent women. METHODS: HSV-2-seropositive women collected daily samples
      of genital secretions while receiving acyclovir or placebo, each for 10 weeks. In
      vitro acyclovir sensitivity testing was performed using the dye uptake assay;
      isolates for which the concentration of acyclovir that inhibited cytopathic
      effect by 50% (EC50) was > or = 3 microg/mL were defined as resistant. RESULTS: A
      total of 351 isolates from 26 women were tested (median, 10 isolates/woman
      [range, 3-45 isolates/woman]). The median EC50 was 0.91 microg/mL. Overall, 7
      isolates (1.7%) from 6 women had EC50 values > or = 3 microg/mL. None of the
      women was receiving acyclovir when the acyclovir-resistant isolates were
      detected. Acyclovir-sensitive and acyclovir-resistant isolates were detected in
      samples collected on the same day from separate anatomic sites in 3 women. The
      acyclovir-resistant isolates were transient, because acyclovir-sensitive isolates
      were obtained before and after the acyclovir-resistant isolates from 5 women were
      detected. CONCLUSIONS: Among immunocompetent women, the finding of acyclovir
      resistant HSV-2 isolates likely represents transient mucosal variants and does
      not predict treatment failure.

PMID- 16107967
TI  - Praziquantel treatment of individuals exposed to Schistosoma haematobium enhances
      serological recognition of defined parasite antigens.
AB  - BACKGROUND: Schistosomiasis is a major parasitic disease affecting >200 million
      people in the developing world, and 400 million people are at risk for infection.
      This study aimed to identify and compare proteins recognized by serum samples
      from schistosome-exposed individuals before and after curative praziquantel
      treatment. METHODS: Proteins recognized by pooled serum samples from Schistosoma
      haematobium-exposed Zimbabweans were determined by 2-dimensional Western blotting
      and identified by mass spectrometry. RESULTS: Serum samples recognized 71 spots,
      which resolved to 26 different characterized proteins. Eleven of these proteins
      have not previously been shown to be immunogenic in natural human infection or in
      experimental models of schistosomiasis, making them novel antigens in the
      parasite. Pretreatment serum samples recognized 59 spots, which resolved to 21
      different identified proteins. Posttreatment serum samples recognized an
      additional 12 spots, which resolved to 8 different identified proteins. Of these
      8 proteins, 3 had putative isoforms recognized before treatment, and 5
      (calreticulin, tropomyosin 1, tropomyosin 2, paramyosin, and triose phosphate
      isomerase) did not. CONCLUSIONS: This study is the most comprehensive
      characterization of S. haematobium antigens to date and describes novel antigens
      in all schistosome species. Posttreatment results are consistent with
      praziquantel treatment inducing quantitative and qualitative changes in
      schistosome-specific antibody responses.

PMID- 16107968
TI  - Plasmodium falciparum antigenic variation: relationships between in vivo
      selection, acquired antibody response, and disease severity.
AB  - BACKGROUND: Variant surface antigens (VSA) on Plasmodium falciparum-infected
      erythrocytes are potentially important targets of immunity to malaria. We
      previously identified a VSA phenotype--VSA with a high frequency of antibody
      recognition (VSA(FoRH))--that is associated with young host age and severe
      malaria. We hypothesized that VSA(FoRH) are positively selected by host molecules
      such as intercellular adhesion molecule 1 (ICAM1) and CD36 and dominate in the
      absence of an effective immune response. Here, we assessed, in 115 Kenyan
      children, the potential role played by in vivo selection pressures in either
      favoring or selecting against VSA(FoRH) among parasites that cause malaria.
      METHODS: We tested for associations between VSA(FoRH) and (1) the repertoire of
      VSA antibodies carried by children at the time of acute malaria and (2)
      polymorphisms in ICAM1 (K29M) and CD36 (T188G) that could potentially reduce the
      positive selection of VSA(FoRH). RESULTS: An expected negative association
      between VSA antibody repertoire and VSA(FoRH) was observed in children with
      nonsevere malaria. However, this association did not extend to children with
      severe malaria, many of whom apparently had well-developed VSA antibody responses
      despite being infected by parasites expressing VSA(FoRH). There was no evidence
      for involvement of CD36 or ICAM1 in positive selection of VSA(FoRH). On the
      contrary, a weak positive association between carriage of the CD36 (T188G) allele
      and VSA(FoRH) was observed in children with severe malaria. CONCLUSION: The
      association between the VSA(FoRH) parasite phenotype and severe malaria cannot be
      explained simply in terms of the total repertoire of VSA antibodies carried at
      the time of acute disease.

PMID- 16107969
TI  - Turnover of neutrophils mediated by Fas ligand drives Leishmania major infection.
AB  - Apoptosis mediated by Fas ligand (FasL) initiates inflammation characterized by
      neutrophilic infiltration. Neutrophils undergo apoptosis and are ingested by
      macrophages. Clearance of dead neutrophils leads to prostaglandin- and
      transforming growth factor-beta-dependent replication of Leishmania major in
      macrophages from susceptible mice. How L. major induces neutrophil turnover in a
      physiological setting is unknown. We show that BALB/c FasL-sufficient mice are
      more susceptible to L. major infection than are FasL-deficient mice. FasL
      promotes the apoptosis of infected resident macrophages and attracts neutrophils.
      Furthermore, FasL-sufficient neutrophils exacerbate L. major replication in
      macrophages, whereas FasL-deficient neutrophils induce parasite killing. These
      contrasting effects are due to delaying apoptosis and the clearance of FasL
      deficient neutrophils. The transfer of neutrophils exacerbates infection in FasL
      sufficient mice but reduces infection in FasL-deficient mice. Depletion of
      neutrophils abolishes the susceptibility of FasL-sufficient mice. These data
      illustrate a deleterious role of the FasL-mediated turnover of neutrophils on L.
      major infection.

PMID- 16107970
TI  - Tropical spastic paraparesis/human T leukemia virus type 1-associated myelopathy
      in HIV type 1-coinfected patients.
AB  - BACKGROUND: Tropical spastic paraparesis/human T leukemia virus type 1 (HTLV-1)
      associated myelopathy (TSP/HAM) is rarely reported in the United States. The
      causative agents of TSP/HAM are HTLV-1 and, possibly, its cosmopolitan variant,
      human T leukemia virus type 2 (HTLV-2). Among HTLV-1- or HTLV-2-monoinfected
      individuals, the estimated lifetime risk for development of TSP/HAM is <2%.
      However, it has been suggested that HIV/HTLV coinfection may increase the risk
      for development of TSP/HAM. METHODS: A total of 2239 human immunodeficiency virus
      (HIV)-infected patients were tested for HTLV-1 and HTLV-2 infection at the New
      Orleans Outpatient Clinic (Louisiana) during the period 1991-1998. HTLV-1
      infected patients with suspected myelopathy were referred for additional
      evaluation. RESULTS: Four cases of TSP/HAM (9.7%) were identified among 41
      individuals with Western blot-confirmed HTLV-1 infection. The diagnosis was
      confirmed with use of molecular diagnostic assays and viral isolation. No TSP/HAM
      cases were identified among 65 patients with HIV-HTLV-2 coinfection. An
      additional patient with HIV-HTLV-1 coinfection also received a diagnosis of
      TSP/HAM at the New Orleans Veteran's Affairs HIV Outpatient Clinic (Louisiana).
      All patients had normal CD4+ T cell counts at the time of diagnosis. CONCLUSIONS:
      Given the high rates of HIV-HTLV coinfection in the United States, a heightened
      suspicion for TSP/HAM should be considered in HIV-infected patients who present
      with normal CD4+ T cell counts and myelopathy in the absence of other acquired
      immunodeficiency syndrome-defining conditions.

PMID- 16107971
TI  - Dropped gallstone as a nidus of intra-abdominal abscess complicated by empyema.
AB  - We describe a patient who developed an intra-abdominal abscess and empyema from a
      dropped gallstone at the time of laparoscopic cholecystectomy 1.5 years ago. As
      minimally invasive surgeries become conventional, clinicians should be aware of
      this increasingly common complication.

PMID- 16107972
TI  - Comparative prevalence of superantigen genes in Staphylococcus aureus isolates
      causing sepsis with and without septic shock.
AB  - BACKGROUND: Staphylococcus aureus superantigens are associated with the
      pathogenesis of toxic shock syndrome, but their involvement in septic shock is
      unknown. METHODS: We compared the distribution of 11 superantigen genes in S.
      aureus blood culture isolates obtained from patients with sepsis who did and did
      not have septic shock (19 and 61 patients, respectively), as well as from
      patients with suppurative infections (101 patients) and patients with
      colonization (25 patients). RESULTS: The prevalence of the enterotoxin A gene
      (sea) increased significantly with the severity of infection (P<.001), whereas
      the prevalence of the enterotoxin gene cluster (egc) decreased significantly
      (P=.009). CONCLUSION: Enterotoxin A (SEA) might play a key role in sea-positive
      S. aureus sepsis by triggering over-expression of inflammatory mediators
      associated with shock. Novel treatments targeting superantigens, especially the
      sea gene, might be beneficial in the treatment of S. aureus sepsis.

PMID- 16107973
TI  - Does sporadic Listeria gastroenteritis exist? A 2-year population-based survey in
      Nova Scotia, Canada.
AB  - BACKGROUND: Febrile gastroenteritis due to Listeria monocytogenes (LM) has been
      primarily described in foodborne outbreaks. We decided to determine the incidence
      of sporadic, febrile gastroenteritis due to LM in a large, well-defined North
      American population over a 2-year period and to compare these cases to sporadic
      cases of Campylobacter and Salmonella infections occurring concurrently in the
      community. METHODS: From 1 September 2002 through 31 August 2004, all stool
      specimens submitted for evaluation of diarrheal illness to a public health
      laboratory and to a children's hospital serving a population of approximately
      350,000 were examined for the presence of Listeria species. Patients identified
      as having LM in their stool samples were matched with 2 temporally-matched
      patients with cultures positive for Campylobacter and Salmonella species.
      Patients with LM and control patients were contacted by telephone, and they
      answered a questionnaire that examined clinical features and risk factors for
      diarrheal illness. RESULTS: A total of 7775 stool specimens were submitted during
      the period 1 September 2002-31 August 2004. Thirty-nine Listeria species were
      recovered. Seventeen of the species were LM, 13 were Listeria innocua, 3 were
      Listeria welshimeri, 1 was Listeria grayi, and 4 were other species. Pulsed-field
      gel electrophoresis results demonstrated no temporal or other clusters, and no
      seasonality was noted for isolates of LM. Preexisting gastrointestinal problems
      were much more common in patients with LM (P=.001) than in patients with
      Campylobacter or Salmonella infections. CONCLUSIONS: Sporadic gastroenteritis due
      to LM appears to be an uncommon illness, and routine screening of stool samples
      for LM remains unwarranted. Preexisting gastrointestinal disease may be a risk
      factor for infection of the gastrointestinal tract with LM.

PMID- 16107974
TI  - Enterohemorrhagic Escherichia coli in human infection: in vivo evolution of a
      bacterial pathogen.
AB  - BACKGROUND: Enterohemorrhagic Escherichia coli (EHEC) cause most cases of the
      hemolytic uremic syndrome (HUS) worldwide. To investigate genetic changes in EHEC
      during the course of human infection, we analyzed consecutive stool samples and
      shed isolates from patients with HUS, focusing on the genes encoding Shiga toxin
      (stx) and intimin (eae). METHODS: Sequential stool samples from 210 patients with
      HUS were investigated for the persistence of E. coli strains harboring stx and/or
      eae. Initial stool samples were collected during the acute phase of HUS, and
      subsequent stool samples were collected 3-16 days later (median interval, 8
      days). RESULTS: Organisms that were stx and eae positive (stx+/eae+ strains;
      n=137) or stx negative and eae positive (stx-/eae+ strains; n=5) were detected in
      the initial stool samples from 142 patients. Subsequently, the proportion of
      those who shed stx+/eae+ strains decreased to 13 of 210 patients, whereas the
      proportion of those who shed strains that were stx-/eae+ increased to 12 of 210
      patients. Seven patients who initially excreted strains that were stx+/eae+ shed,
      at second analysis, stx-/eae+ strains of the same serotypes; they had no free
      fecal Shiga toxin at follow-up. Comparison of the initial and follow-up isolates
      from these patients with use of molecular-epidemiological methods revealed loss
      of stx genes and genomic rearrangement. CONCLUSIONS: We demonstrate the loss of a
      critical bacterial virulence factor from pathogens during very brief intervals in
      the human host. These genetic changes have evolutionary, diagnostic, and clinical
      implications. Generation of stx- mutants might contribute to subclonal evolution
      and evolutionary success.

PMID- 16107975
TI  - The relentless evolution of pathogenic Escherichia coli.

PMID- 16107976
TI  - Prevalence of and associated risk factors for fluoroquinolone-resistant Neisseria
      gonorrhoeae in California, 2000-2003.
AB  - BACKGROUND: Rates of fluoroquinolone-resistant Neisseria gonorrhoeae (QRNG) are
      increasing worldwide and in California. METHODS: As a supplement to established
      surveillance, the investigation of QRNG in California included expanded
      surveillance in southern California, with in-depth interviews of patients (who
      had QRNG during the period of January 2001-June 2002) and a cross-sectional study
      of patients at 4 sexually transmitted diseases clinics with gonococcal isolates
      that underwent susceptibility testing (for the period of July 2001-June 2002).
      RESULTS: The rate of QRNG increased from <1% in 1999 to 20.2% in the second half
      of 2003. The 2001-2002 expanded surveillance demonstrated that 66 (4.9%) of 1355
      isolates were resistant to fluoroquinolones; the majority of these infections
      occurred after August 2001. Cross-sectional analysis of 952 patients with
      gonorrhea revealed that the prevalence of QRNG varied geographically during 2001
      2002, with the highest rate being in southern California (8.9%) and the lowest
      being in San Francisco (3.6%). The QRNG prevalence was 8.6% among men who have
      sex with men (MSM), 5.1% among heterosexual men, and 4.3% among women. Although
      risk factors for QRNG varied by clinic, multivariate analysis demonstrated
      independent associations with race/ethnicity, recent antibiotic use, and MSM.
      CONCLUSIONS: The emergence and spread of QRNG in California appeared to evolve
      from sporadic importation to endemic transmission among both MSM and
      heterosexuals. Monitoring of both the prevalence of and risk factors for QRNG
      infections is critical for making treatment recommendations and for developing
      interventions to interrupt transmission.

PMID- 16107977
TI  - Challenges of sexually transmitted disease prevention and control: no magic
      bullet, but some bullets would still be appreciated.

PMID- 16107978
TI  - Evaluation of imiquimod 5% cream to modify the natural history of herpes
      labialis: a pilot study.
AB  - BACKGROUND: Imiquimod is currently approved for the treatment of genital warts
      and has been shown to decrease recurrences of genital herpes in the guinea pig
      model of genital herpes. Therefore, we evaluated the safety and potential of
      topical imiquimod to decrease the rate of recurrence in humans with a history of
      recurrent herpes labialis. METHODS: Forty-seven subjects with recurrent herpes
      labialis applied imiquimod 5% (n=30) or vehicle cream (n=17) to recurrent
      lesion(s) on days 1, 3, and 5 of the study (day 1 of observation occurred within
      48 h after recurrence of lesion). Subjects were seen at the study centers between
      each dose and 3 days after application of the final dose or until resolution of
      the lesion. RESULTS: After application to recurrent lesions, local erythema,
      edema, scabbing and/or flaking, pain, burning, and maximal lesion size were
      significantly greater in the imiquimod group than in the vehicle group. The study
      was terminated early because of severe local adverse events that occurred in 5
      recipients of imiquimod. The median time until the next recurrence was, however,
      increased from 50 days in the vehicle group to 91 days in the imiquimod group
      (P=.018). CONCLUSIONS: Application of imiquimod 5% cream to herpes labialis
      lesions was associated with a delay in the time to the first recurrence after
      treatment, but severe local inflammation occurred in some individuals.

PMID- 16107979
TI  - Biosafety level 3 laboratory for autopsies of patients with severe acute
      respiratory syndrome: principles, practices, and prospects.
AB  - BACKGROUND: During the outbreak of the emergent severe acute respiratory syndrome
      (SARS) infection, >30% of the approximately 8000 infected persons were health
      care workers. The highly infectious nature of SARS coronavirus (SARS-CoV)
      compelled our pathologists to consider biosafety issues in the autopsy room and
      for tissue processing procedures. METHODS: A specially designed biosafety level 3
      (BSL-3) autopsy laboratory was constructed and divided into a clean area, a
      semicontaminated area, a contaminated area, and 2 buffer zones. High-efficiency
      particulate air filters were placed in the air supply and exhaust systems.
      Laminar air flow was from the clean areas to the less clean areas. The negative
      pressures of the contaminated, semicontaminated, and clean areas were
      approximately -50 pa, -25 pa, and -5 pa, respectively. Personal protective
      equipment, including gas mask, impermeable protective clothing, and 3 layers of
      gloves worn during autopsies; the equipment was decontaminated before it was
      allowed to exit the facility. Strict BSL-3 practices were followed. RESULTS: When
      a given concentration of particulate sarin simulant was introduced into the
      contaminated area, it could not be detected in either the semicontaminated area
      or clean area, and particles >0.3 microm in size were not detected in the exhaust
      air. A total of 16 complete postmortem examinations for probable and suspected
      SARS were performed during a 2-month period. Of these, 7 reported confirmed cases
      of SARS. None of the 23 pathologists and technicians who participated in these
      autopsies was infected with SARS-CoV. CONCLUSIONS: Our experience suggests that
      BSL-3 laboratory operating principles should be among the special requirements
      for performing autopsies of contaminated bodies and that they can safeguard the
      clinicians and the environment involved in these procedures.

PMID- 16107980
TI  - Characterization of viral agents causing acute respiratory infection in a San
      Francisco University Medical Center Clinic during the influenza season.
AB  - BACKGROUND: With use of polymerase chain reaction (PCR) and a centrifugation
      enhanced viral culture method, we characterized the viruses causing acute
      respiratory infection in adults during an influenza season. METHODS: During
      January-March 2002, nasopharyngeal wash specimens from previously healthy adults
      presenting with respiratory symptoms were evaluated for viral pathogens with
      centrifugation-enhanced viral culture and PCR. RESULTS: The diagnoses in 266
      cases included unspecified upper respiratory infection (in 142 [54%] of the
      cases), acute bronchitis (42 [16%]), sinusitis (23 [9%]), pharyngitis (22 [8%]),
      and pneumonia (17 [6%]). The use of a shell vial assay and PCR identified a
      pathogen in 103 (39%) of the patients, including influenza A or B in 54,
      picornavirus in 28 (including rhinovirus in 24), respiratory syncytial virus
      (RSV) in 12, human metapneumovirus in 4, human coronavirus OC43 in 2, adenovirus
      in 2, parainfluenza virus type 1 in 1, and coinfection with influenza and
      parainfluenza virus type 1 in 2. CONCLUSION: Our findings demonstrate that, even
      during the influenza season, rhinovirus and RSV are prevalent and must be
      considered in the differential diagnosis of adult acute respiratory infection
      before prescribing antiviral medication. Human coronavirus and human
      metapneumovirus did not play a substantial role. PCR was an especially useful
      tool in the identification of influenza and other viral pathogens not easily
      detected by traditional testing methods.

PMID- 16107981
TI  - Diagnostic evaluation for Creutzfeldt-Jakob disease in Massachusetts, 1991-2001.
AB  - BACKGROUND: Surveillance for Creutzfeldt-Jakob disease (CJD) in the United States
      has become a focus of public health attention due to concerns about disease
      acquired through exposure to transmissible spongiform encephalopathy in other
      species. A definitive diagnosis requires neuropathologic examination, yet
      concerns about the invasiveness of procedures and infection control may be
      barriers to brain biopsy or autopsy in patients with suspected CJD. METHODS: We
      reviewed medical records of 50 of the 97 patients identified through the
      Massachusetts Department of Public Health CJD surveillance system for 1991-2001
      and of an additional 21 patients in whom CJD was suspected but later ruled out.
      RESULTS: Of the 50 patients, brain biopsy was performed on 14 (28%), brain biopsy
      or autopsy was performed on 27 (54%), and brain biopsy and autopsy were performed
      on 4 (8%). Brain biopsy or autopsy was declined for an additional 7 patients
      (14%) by family or health care proxy. The proportion of patients on whom brain
      biopsy was performed was inversely correlated with age, with only 9 (21%) of the
      43 patients >60 years old having brain tissue diagnosis. Brain biopsy was
      performed on patients in whom CJD was suspected but ruled out somewhat less often
      than it was for patients with confirmed CJD (4 [19%] of 21 patients vs. 7 [23%]
      of 30 patients, respectively; P=.71). CONCLUSION: The majority of patients with
      CJD-related death whose medical records were available had a brain biopsy or
      autopsy performed or requested (34 [68%] of 50 patients).

PMID- 16107982
TI  - Creutzfeldt-Jakob disease surveillance and diagnosis.

PMID- 16107983
TI  - "Thank you".

PMID- 16107984
TI  - Group B streptococcal infections in elderly adults.
AB  - Elderly adults account for >40% of persons with invasive group B streptococcal
      (GBS) disease and for >50% of GBS-associated deaths in the United States. The
      prevalence of colonization among healthy elderly adults (approximately 25%) is
      similar to that among women of childbearing age. Delineating contributions of
      comorbid conditions, altered integrity of anatomical barriers, and abnormalities
      in immune responses caused by immune senescence to pathogenesis require further
      investigation. Delayed clinical recognition of illness may contribute to poor
      outcome. Skin and soft-tissue infections and bacteremia with no identified focus
      are common manifestations of infection in elderly adults and younger nonpregnant
      adults. Urinary tract infection and pneumonia are presentations more often
      encountered in elderly persons than in younger adults. The safety and
      immunogenicity of GBS serotype V-tetanus toxoid conjugate vaccine in healthy
      elderly persons suggest the potential for vaccination as an approach to
      prevention of invasive GBS infections in elderly persons.

PMID- 16107985
TI  - Overview of nosocomial infections caused by gram-negative bacilli.
AB  - We analyzed data from the National Nosocomial Infections Surveillance (NNIS)
      System from 1986-2003 to determine the epidemiology of gram-negative bacilli in
      intensive care units (ICUs) for the most frequent types of hospital-acquired
      infection: pneumonia, surgical site infection (SSI), urinary tract infection
      (UTI), and bloodstream infection (BSI). We analyzed >410,000 bacterial isolates
      associated with hospital-acquired infections in ICUs during 1986-2003. In 2003,
      gram-negative bacilli were associated with 23.8% of BSIs, 65.2% of pneumonia
      episodes, 33.8% of SSIs, and 71.1% of UTIs. The percentage of BSIs associated
      with gram-negative bacilli decreased from 33.2% in 1986 to 23.8% in 2003. The
      percentage of SSIs associated with gram-negative bacilli decreased from 56.5% in
      1986 to 33.8% in 2003. The percentages pneumonia episodes and UTIs associated
      with gram-negative bacilli remained constant during the study period. The
      proportion of ICU pneumonia episodes associated with Acinetobacter species
      increased from 4% in 1986 to 7.0% in 2003 (P<.001, by the Cochran-Armitage chi2
      test for trend). Significant increases in resistance rates were uniformly seen
      for selected antimicrobial-pathogen combinations. Gram-negative bacilli are
      commonly associated with hospital-acquired infections in ICUs. The proportion of
      Acinetobacter species associated with ICU pneumonia increased from 4% in 1986 to
      7.0% in 2003.

PMID- 16107986
TI  - Perspective on HIV infection and aging: emerging research on the horizon.
AB  - A greater prevalence of human immunodeficiency virus (HIV)-infected individuals
      aged >50 years is projected. This epidemiologic trend will continue to increase
      as a result of not only greater survival rates among HIV-infected patients who
      receive treatment, but also of delayed recognition of older individuals with
      occult HIV disease. Historically, it was thought that, despite viral responses to
      highly active antiretroviral therapy (HAART) among older individuals that
      approximate those of younger individuals, older persons infected with HIV could
      not mount as vigorous an immune response as do younger HIV-infected individuals.
      However, recent evidence suggests that older HIV-infected individuals may do just
      as well, because they may be more compliant with their antiretroviral regimens.
      Limited data are available on the safety and tolerability of HAART in this
      population. Emerging evidence suggests that metabolic, neuropsychiatric, and
      cardiovascular morbidities could be exacerbated by use of antiretrovirals or by
      HIV infection itself. Additional research is needed to optimize the care of older
      HIV-infected patients.

PMID- 16107987
TI  - Mortality in an urban cohort of HIV-infected and at-risk drug users in the era of
      highly active antiretroviral therapy.
AB  - BACKGROUND: Mortality trends among drug users in the era of highly active
      antiretroviral therapy (HAART) remain unclear. METHODS: We examined mortality
      rates, causes of death, and predictors of mortality in 398 human immunodeficiency
      virus (HIV)-infected and 656 at-risk drug users for the period of 1996-2001.
      National death index reports were used to confirm deaths, and causes of death
      were derived from medical records. Cox proportional hazards models were used to
      determine factors associated with mortality. RESULTS: During 1996-2001, mortality
      rates in HIV-infected and HIV-uninfected participants were 7.3 and 1.5 deaths per
      100 person-years, respectively (P<.001). The mean age at the time of death was
      43.6 years for HIV-infected subjects and 47.7 years in HIV-uninfected subjects
      (P<.001). For 398 HIV-infected participants who were observed for 1443 person
      years, death rates decreased from 11.4 to 5.4 deaths per 100 person-years over
      the 6-year period (P=.04). Among all participants, causes of death were as
      follows: HIV/AIDS, 27% of subjects; substance abuse, 31%; bacterial infection,
      25%; other medical illness, 14%; and violence, 3%. Persons who initiated HAART at
      a CD4+ lymphocyte count of 201-350 cells/mm3 experienced improved survival,
      compared with those who initiated it at a CD4+ lymphocyte count of < or =200
      cells/mm3 (P=.01). In a multivariate Cox model of HIV-infected subjects, factors
      independently associated with mortality included receipt of HAART (adjusted
      hazard ratio [HR(adj)], 0.44; 95% confidence interval [CI], 0.28-0.68) and CD4+
      lymphocyte count of < or =200 cells/mm3 (HR(adj), 4.23; 95% CI, 2.24-7.60). Use
      of methadone or illicit drugs did not predict mortality. CONCLUSIONS: To further
      reduce mortality among drug users, interventions aimed at improving HAART use are
      warranted. Preventive health and timely management of treatable conditions, such
      as bacterial infections, also needs emphasis.

PMID- 16107988
TI  - Mortality among urban drug users and the impact of highly active antiretroviral
      therapy.

PMID- 16107989
TI  - A programmable prompting device improves adherence to highly active
      antiretroviral therapy in HIV-infected subjects with memory impairment.
AB  - Background. Patients cite "forgetting" as a reason for nonadherence to highly
      active antiretroviral therapy (HAART). We measured the effect of a memory
      prompting device on adherence to HAART in memory-intact and memory-impaired human
      immunodeficiency virus (HIV)-infected subjects.Methods. The study was a
      prospective, randomized, controlled trial involving 64 HIV-infected adults. The
      intervention was the Disease Management Assistance System (DMAS) device, combined
      with monthly adherence counseling. Control subjects received only adherence
      counseling. The DMAS was programmed with HAART regimen data to provide verbal
      reminders at dosing times. Adherence was measured for 24 weeks using electronic
      drug exposure monitor (eDEM) caps.Results. A total of 58 subjects completed the
      24-week study period; 28 were HAART naive (12 DMAS users and 16 control
      subjects). Mean adherence scores did not differ significantly between DMAS users
      (80%) and control subjects (65%). Post hoc analysis of 31 memory-impaired
      subjects (14 DMAS users and 17 control subjects) revealed significantly higher
      adherence rates among DMAS users (77%), compared with control subjects (57%)
      (P=.001). However, analysis of memory-intact subjects showed that adherence was
      not significantly improved for DMAS users (83%), compared with control subjects
      (77%) (P=.25). At week twelve, 38% of the DMAS users and 14% of the control
      subjects had an undetectable plasma HIV RNA load (P=.014), and at week 24, the
      plasma HIV RNA load was undetectable for 34% of the DMAS users and 38% of the
      control subjects (P=.49). CD4(+) cell counts did not differ between the study
      arms. Virological and immunological responses were not related to DMAS use in
      memory-impaired subjects.Conclusion. The DMAS prompting device improved adherence
      for memory-impaired subjects but not for memory-intact subjects.

PMID- 16107990
TI  - Risk of selecting de novo drug-resistance mutations during structured treatment
      interruptions in patients with chronic HIV infection.
AB  - BACKGROUND: Structured treatment interruption (STI) may allow viral replication
      in the presence of decreased plasma drug levels, with risk of selection of
      resistance mutations. METHODS: For patients recruited for an STI study, genotypic
      resistance testing was performed at baseline (before receipt of any treatment),
      immediately before the STI, and 2 weeks after each interuption of therapy.
      RESULTS: During 20 (18%) of 112 STI cycles (95% CI, 11%-26%), resistance
      mutations were selected; 6% of the mutations were de novo (i.e., not detected
      before the start of STI), and 12% were archived mutations (i.e., mutations
      already detected before the STI). Overall, resistance mutations during STI were
      selected in 9 (26%) of 35 patients; 5 (14%) of the mutations were de novo, and 4
      (12%) were archived mutations. Mutations conferring resistance to nonnucleoside
      reverse-transcriptase inhibitors (NNRTIs) were selected in 3 (23%) of 13 patients
      receiving NNRTI-based regimens (all mutations were de novo). Mutations conferring
      resistance to lamivudine were selected in 9 (50%) of 18 patients receiving
      lamivudine-containing regimens (4 [22%] were de novo, and 5 [28%] were archived
      mutations). Mutations conferring resistance to nucleoside reverse-transcriptase
      inhibitors (NRTIs), excluding the M184V mutation, were selected in 2 (6%) of 35
      recipients of NRTIs (1 [3%] of these mutations was de novo, and 1 [3%] was an
      archived mutation. Finally, mutations conferring resistance to protease
      inhibitors were selected in none of the 22 patients receiving protease
      inhibitors. In most cases, de novo and archived mutations were selected during
      the first STI cycle, and their number did not increase during successive cycles.
      Plasma viral load decreased to undetectable levels in all the patients when the
      earlier drug regimen was reintroduced. CONCLUSIONS: Genotypic mutations are
      selected during STI in a high proportion of patients (especially in patients
      receiving NNRTIs or lamivudine). Approximately one-half of selected mutations
      were archived mutations. Patients who had archived mutations did not have a
      higher risk of accumulating new mutations than did patients who were infected
      with wild-type virus before the STI.

PMID- 16107991
TI  - Buprenorphine: its role in preventing HIV transmission and improving the care of
      HIV-infected patients with opioid dependence.
AB  - In the United States, approximately 25% of the 40,000 new human immunodeficiency
      virus (HIV) infections each year are secondary to injection drug use. Worldwide,
      there are an estimated 12.6 million injection drug users, and 10% of HIV
      infections (420,000 infections in 2003) are associated with this practice.
      Buprenorphine is a new medication used to treat opioid dependence that shows
      promise for reducing the rate of HIV transmission and improving the care of
      opioid-dependent patients with HIV infection. Although buprenorphine faces fewer
      clinical and regulatory barriers than does methadone, the optimal strategy for
      integration of office-based treatment of opioid dependence and HIV disease is an
      area of ongoing research. This review addresses the introduction of
      buprenorphine, in terms of public health, policy, and clinical implications for
      HIV-infected patients and for HIV care providers.

PMID- 16107992
TI  - Superiority of protease inhibitors over nonnucleoside reverse-transcriptase
      inhibitors when highly active antiretroviral therapy is resumed after treatment
      interruption.
AB  - Forty-five human immunodeficiency virus (HIV)-infected patients stopped taking
      treatment but resumed taking it thereafter. All 11 who resumed treatment with
      their prior protease inhibitor (PI)-based regimen reattained an undetectable
      virus load, whereas this occurred for only 15 (44%) of 34 patients who resumed
      nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based treatment (P<.001).
      Distinct pharmacokinetics and resistance barriers may result in different
      performances for PIs and NNRTIs after treatment interruptions.

PMID- 16107993
TI  - Compromised immunologic recovery in treatment-experienced patients with HIV
      infection receiving both tenofovir disoproxil fumarate and didanosine in the TORO
      studies.
AB  - The effect of therapy with a combination of tenofovir and full-dose didanosine on
      increases in CD4+ cell count was examined in 2 large trials of treatment
      experienced patients with human immunodeficiency virus (HIV) infection (the T-20
      versus Optimized Regimen Only [TORO] 1 and 2 clinical trials). Individuals
      receiving both agents showed little additional increase in CD4+ cell count after
      week 8 of therapy, whereas those receiving 1 or neither of the agents had
      continuous increases over a 48-week period.

PMID- 16107994
TI  - Hepatitis C virus infection in HIV type 1-infected individuals does not
      accelerate a decrease in the CD4+ cell count but does increase the likelihood of
      AIDS-defining events.
AB  - Human immunodeficiency virus type 1 (HIV-1) appears to adversely affect hepatitis
      C, but whether hepatitis C virus (HCV) has a reciprocal effect on HIV-1 infection
      remains a point of controversy. In a multivariate analysis of a cohort of 5832
      individuals, we found that individuals coinfected with HCV and HIV-1 (prevalence
      of coinfection, 5.8%) had a CD4+ cell count that decreased at a rate similar to
      that for individuals infected with HIV-1 alone. However, coinfection was
      associated with a statistically significant increased likelihood of onset of an
      acquired immunodeficiency syndromedefining illness or developing a CD4+ cell
      count of <200 cells/mm3, compared with infection with HIV-1 alone (hazard ratio,
      1.52; 95% confidence interval, 1.072.17). Patients who were naive to highly
      active antiretroviral therapy were significantly less likely to progress to
      either end point, because of their higher CD4+ cell counts. In conclusion, there
      was an increased number of adverse events in coinfected individuals, compared
      with individuals infected with HIV-1 alone.

PMID- 16107995
TI  - HIV testing and privacy laws.

PMID- 16107996
TI  - Pinta: specific disease or anomalous skin reaction?

PMID- 16107998
TI  - Systemic steroid treatment of paradoxical upgrading reaction in patients with
      lymph node tuberculosis.

PMID- 16108000
TI  - John E. Bennett Forum on Deep Mycoses Study Design 2004: Candidiasis and salvage
      therapy for aspergillosis.

PMID- 16108001
TI  - Candiduria.
AB  - Candiduria is a common finding. Yeasts can be detected in urine that is
      contaminated during collection, in patients who have bladder colonization, and in
      patients who have upper urinary tract infection that developed either from
      retrograde spread from the bladder or hematogenous spread from a distant source.
      Most patients with candiduria are asymptomatic. The rate of development of
      complications is not known but appears to be low; candidemia rarely results from
      asymptomatic candiduria unless obstruction is present or instrumentation of the
      urinary tract is done. Unfortunately, there are no established diagnostic tests
      that reliably distinguish infection from colonization. Guidelines for the
      treatment of candiduria, based almost entirely on anecdotal reports and expert
      opinions, rather than controlled clinical trials, have been suggested by the
      Infectious Diseases Society of America. Until reliable methods to distinguish
      infection from colonization are developed, further treatment trials are unlikely
      to provide information to guide the clinician in the treatment of candiduria.

PMID- 16108002
TI  - Should the consensus guidelines' specific criteria for the diagnosis of invasive
      fungal infection be changed?
AB  - The introduction of a standardized set of criteria to define invasive fungal
      infections has fulfilled a need. The criteria make comparisons between various
      clinical studies more easy and facilitate discussions of trial designs. However,
      application of the criteria in practice has indicated that some criteria for
      possible disease (in particular, antibiotic-resistant fever during neutropenia)
      are rather unspecific and allow the inclusion of patients who are unlikely to
      have an invasive fungal infection in trials. On the other hand, new diagnostic
      tools have been validated sufficiently to consolidate the effect of the criteria
      on the diagnosis of invasive fungal infections. Finally, it has become evident
      that changing medical practices with deleterious consequences for the innate
      immune system extend the population at risk for invasive fungal infections. This
      combination of factors has urged researchers to reconsider the continuing
      appropriateness of the current definitions.

PMID- 16108003
TI  - Design issues in studies evaluating diagnostic tests for aspergillosis.
AB  - Although invasive aspergillosis is recognized as an increased concern for
      immunosuppressed patients, establishing an early diagnosis remains a challenge.
      Current methods for diagnosis, including sensitive radiography and invasive
      procedures to identify organisms in affected tissues, provide an early diagnosis
      for only a small proportion of patients infected with Aspergillus species. The
      availability of a standardized assay to detect circulating Aspergillus
      galactomannan, the BioRad Platelia Aspergillus galactomannan enzyme immunoassay,
      should be considered as a valuable tool. However, at present, clinical utility is
      hampered by controversies surrounding the performance of the test and an apparent
      lack of definitive data. These controversies emphasize the complexity inherent in
      analyzing diagnostic tests for aspergillosis. The widespread availability of a
      standardized assay may now allow us to address the multiple sources of
      variability and bias via large, cooperative studies.

PMID- 16108004
TI  - Salvage therapy for aspergillosis.
AB  - Participants at the John E. Bennett Forum on Design of Clinical Trials for Fungal
      Infections suggested guidelines for the regulatory approval of drugs solely on
      the basis of salvage therapy--that is, the use of an unlicensed drug to treat
      patients who have experienced failure with or who have been intolerant of an
      approved drug. The topics covered included requirements for study design (i.e.,
      the design allows the comparison of comparable items), entry criteria (in
      particular, the duration of therapy before salvage therapy is introduced), and
      outcome criteria that determine whether or not the treatment was successful.

PMID- 16108005
TI  - Bloodstream infections due to Candida species in the intensive care unit:
      identifying especially high-risk patients to determine prevention strategies.
AB  - Nosocomial bloodstream infections due to Candida species are associated with a
      40% crude (total) mortality rate in the United States. The attributable mortality
      rate defines the number of deaths due directly to the infection and represents
      the proportion of the total number of deaths influenced by the use of anti
      infectives. We used 4 defined risk factors to create a conditional logistic
      regression model of individual patients' risk of candidemia and then examined the
      possibility of using a calculated risk threshold to begin treatment with anti
      Candida antibiotics. We subsequently examined the number needed to treat (NNT) to
      prevent a single death related to bloodstream infection due to Candida species.
      By use of our model and assuming a 33% threshold for treating with an antibiotic,
      which is assumed to prevent 65% of candidal bloodstream infections, we show that
      the NNT would be 7 patients. Use of defined risk factors to select patients who
      are at high risk for candidemia and treatment with effective antibiotics would be
      an efficient way to reduce infection-related deaths.

PMID- 16108006
TI  - Optical imaging of pancreatic beta cells in living mice expressing a mouse
      insulin I promoter-firefly luciferase transgene.
AB  - We generated transgenic mice expressing firefly (Photinus pyralis) luciferase
      (luc) under the control of the mouse insulin I promoter (MIP). The mice have
      normal glucose tolerance and pancreatic islet architecture. The luciferase
      expressing beta cells can be readily visualized in living mice using whole-body
      bioluminescent imaging. The MIP-luc transgenic mice may be useful for monitoring
      changes in beta cell function or mass in living animals with normal or altered
      metabolic states.

PMID- 16108007
TI  - The electrophysiological effects of neurotensin on spontaneously active neurons
      in the nucleus accumbens: an in vivo study.
AB  - Considerable evidence obtained from neuroanatomical and neurochemical studies
      suggests an interaction between the endogenous tridecapeptide neurotensin (NT)
      and central nervous system dopamine (DA) neurons. Centrally administered NT
      blocks many of the actions of synaptic DA in limbic brain areas; the specific
      mechanism and receptors involved remain under investigation. The
      electrophysiological effects of NT were studied using extracellular recording
      techniques and iontophoretic application in 243 spontaneously active neurons in
      the nucleus accumbens (NAc), with a positive/negative waveform. NT was directly
      applied to 208 neurons in a pulsatile fashion by iontophoresis (21+/-1 nA). NT
      had no effect on the firing rate of 120 neurons ((0.31+/-0.72)%), decreased the
      firing rate in 51 neurons ((-27.87+/-1.52)%), and increased the firing rates of
      37 neurons ((33.38+/-2.6)%). One hundred ninety nine (81.9%) of the neurons
      studied were sensitive to iontophoretically applied DA (>15% decrease in firing
      rate). The effects of continuous NT application on DA-induced inhibitions were
      studied in 169 neurons. NT attenuated neuronal responses to directly applied DA
      by (49.95+/-4.52)%, with antagonism in the "core" subregion (n=96) of (33.41+/
      7.75)% when compared with antagonism in the "shell" subregion (n=71) of (61.39+/
      5.2)%. The effects of NT on DA were consistent and independent of the effects of
      NT alone. These data provide further evidence that NT functions as a true
      neuromodulator in the NAc, exerting minimal direct effects, but blocking the
      actions of DA.

PMID- 16108008
TI  - Characterization of medial septal glutamatergic neurons and their projection to
      the hippocampus.
AB  - The two neuronal populations that have been typically investigated in the septum
      use acetylcholine and GABA as neurotransmitters. The existence of noncholinergic,
      non-GABAergic, most likely glutamatergic septal neurons has recently been
      reported. However, their morphological characteristics, numbers, distribution,
      and connectivity have not been determined. Furthermore, the projection of septal
      glutamatergic neurons to the hippocampus has not been characterized. To address
      these issues, subpopulations of cholinergic and GABAergic neurons were identified
      by immunohistochemistry. In addition, the retrograde tracer fluorogold was
      injected into the hippocampus to determine the characteristics of a glutamatergic
      septo-hippocampal projection. Our work revealed that although glutamatergic
      neurons are found throughout the septum, they concentrate in medial septal
      regions. Using stereological probes, approximately 16,000 glutamatergic neurons
      were estimated in the medial septal region. Triple immunostaining showed that
      most glutamatergic neurons do not immunoreact with cholinergic or GABAergic
      neuronal markers (anti-ChAT or anti-GAD67 antibodies, respectively). Fluorogold
      injections into CA1, CA3, and dentate gyrus of the hippocampus showed that septal
      glutamatergic neurons project to each of these hippocampal regions, forming
      approximately 23% of the septo-hippocampal projection. Most cell bodies of septo
      hippocampal glutamatergic neurons were located in the medial septum. The
      remaining cell bodies were found in the diagonal band. This data shows that
      glutamatergic neurons constitute a significant neuronal population in the septum
      and that a subpopulation of these neurons projects to hippocampal regions. Thus,
      the septo-hippocampal projection needs to be reconsidered as a three
      neurotransmitter pathway.

PMID- 16108009
TI  - Aberrant promoter methylation of multiple genes during multistep pathogenesis of
      colorectal cancers.
AB  - Aberrant methylation of 5'gene promoter regions associated with gene silencing is
      an epigenetic phenomenon responsible for silencing of tumor suppressor genes in
      many cancer types. The aims of our study were to study the role of methylation of
      a large panel of genes during multistage pathogenesis and to correlate our
      findings with patient age and other clinico-pathological features. We
      investigated the aberrant promoter methylation profile of 19 genes in 92
      colorectal cancers (CRCs) and corresponding nonmalignant epithelia (NME) (n =
      57), and selected 15 genes for studying 26 colorectal adenomas (CAs). On the
      Basis of our results, the genes could be divided into 3 groups. Group 1 consisted
      of 13 genes whose methylation was tumor-specific. For 8 of these genes, the
      methylation frequencies in CAs were similar to those of CRCs, but significantly
      different from the frequencies in NME. Group 2, consisting of 2 genes
      demonstrating little or no methylation, were present in any sample type. In Group
      3, consisting of 4 genes, relatively frequent methylation was present in both
      CRCs and NME, and the differences between these specimen types were not
      significant. Methylation of Group 1 genes were tightly correlated with each
      other, and these genes demonstrated increased methylation frequencies in CRCs
      with increasing age. Methylation was not correlated with other clinico
      pathological features. In general, methylation frequencies of CAs were
      intermediate between CRCs and NME. Our study constitutes the most comprehensive
      methylation profile of CRCs, demonstrates that methylation commences early during
      CRC pathogenesis and is an age-related phenomenon.

PMID- 16108010
TI  - Theta oscillation-coupled dendritic spiking integrates inputs on a long time
      scale.
AB  - Persistent neural activity lasting for seconds after transient stimulation has
      been observed in several brain areas. This activity has been taken to be
      indicative of the integration of inputs on long time scales. Passive membrane
      properties render neural time constants to be on the order of milliseconds.
      Intense synaptic bombardment, characteristic of in vivo states, was previously
      shown to further reduce the time scale of effective integration. We explored how
      long-term integration in single cells could be supported by dendritic spikes
      coupled with the theta oscillation, a prominent brain rhythm often observed
      during working memory tasks. We used a two-compartmental conductance-based model
      of a hippocampal pyramidal cell to study the interplay of intrinsic dynamics with
      periodic inputs in the theta frequency band. We show that periodic dendritic
      spiking integrates inputs by shifting the phase relative to an external
      oscillation, since spiking frequency is quasi-linearly modulated by current
      injection. The time-constant of this integration process is practically infinite
      for input intensities above a threshold (the integration threshold) and can be
      still several hundred milliseconds long below the integration threshold. The
      somatic compartment received theta frequency stimulation in antiphase with the
      dendritic oscillation. Consequently, dendritic spikes could only elicit somatic
      action potentials when they were sufficiently phase-shifted and thus coincided
      with somatic depolarization. Somatic depolarization modulated the frequency but
      not the phase of firing, endowing the cell with the capability to code for two
      different variables at the same time. Inputs to the dendrite shifted the phase of
      dendritic spiking, while somatic input was modulating its firing rate. This
      mechanism resulted in firing patterns that closely matched experimental data from
      hippocampal place cells of freely behaving rats. We discuss the plausibility of
      our proposed mechanism and its potential to account for the firing pattern of
      cells outside the hippocampus during working memory tasks.

PMID- 16108011
TI  - Osteoporosis in Parkinson's disease.
AB  - There are few studies of osteoporosis in Parkinson's disease (PD). We assessed
      the prevalence of osteoporosis in a PD clinic cohort. All subjects with a
      confirmed diagnosis of PD attending a clinic were invited to participate. All
      consenting subjects had bone density measured by dual energy X-ray absorptiometry
      scanning. Further data, including demography, disease duration, and disease
      severity, were collected. One hundred five subjects participated; median age was
      75 (54-92) years. Fifty-one (49%) patients were men. Of the men: median T score, 
      1.3 (range, -4.7 to 3.8); median Z score, 0.0 (-3.2 to 4.7); diagnostic
      categories: osteoporosis, 20%; osteopenia, 41%; normal, 39%. Of the women: median
      T score -2.7 (-4.7 to 1.4); median Z score, -0.25 (-2.6 to 4.2); diagnostic
      categories: osteoporosis, 63%; osteopenia, 28%; and normal, 9%. Whole sample:
      osteoporosis, 42%; osteopenia, 34%; and normal, 24%. There were associations
      between age, depression, disease duration, and osteoporosis but not with disease
      severity. Female gender was an independent predictor of osteoporosis. The
      prevalence of osteoporosis/osteopenia is considerable in PD patients but does not
      exceed that of other people of similar age. Osteoporosis/osteopenia was present
      in almost all women of this age group with PD.

PMID- 16108012
TI  - Brisk deep-tendon reflexes as a distinctive phenotype in an Argentinean
      spinocerebellar ataxia type 2 pedigree.
AB  - Slow saccades, postural/intention tremor, peripheral neuropathy, and decreased
      deep-tendon reflexes are valuable neurological signs for clinical suspicion of
      spinocerebellar ataxia type 2 (SCA2). We report the presence of abnormally brisk
      deep-tendon reflexes in nonsymptomatic carriers and mildly and severely affected
      subjects of a large Argentinean SCA2 pedigree. The identification of this
      distinctive SCA2 phenotype in an entire pedigree reinforces the current concept
      that clinical algorithms are of limited value as indicators for genetic testing
      in SCA. Combined with published pedigrees of SCA2 manifesting as levodopa
      responsive parkinsonism, this finding suggests that modifier genes could
      influence the clinical phenotype of SCA2.

PMID- 16108013
TI  - Small interfering RNA targeting survivin sensitizes lung cancer cell with mutant
      p53 to adriamycin.
AB  - Survivin is a member of the inhibitor of apoptosis protein (IAP) family that is
      specifically overexpressed in cancer tissues. p53 is one of the tumor suppressor
      genes; its induction in response to DNA damage causes apoptosis and correlates
      with drug sensitivity. To investigate the possible regulation of survivin by p53,
      we examined the level of survivin expression in lung cancer cell lines in
      response to adriamycin. Levels of survivin mRNA and protein in cell lines with
      wild-type p53 decreased dramatically after p53 induction, but no such reduction
      of survivin was observed in cell lines with mutated or null p53. Inhibition of
      wild-type p53 in A549 cells by small interfering (si) RNA significantly
      upregulated the expression of survivin. Survivin inhibition by siRNA in PC9 cells
      with mutated p53 significantly depressed cell proliferation. To investigate the
      sensitivity of cancer cells to adriamycin after inhibition of survivin, we
      depressed survivin expression using siRNA, and then added adriamycin at an IC50
      dose. After a further 48 hr incubation with adriamycin, proliferation was
      significantly depressed in the cells treated with siRNA targeting survivin, in
      comparison with siRNA targeting scramble. Furthermore, both TUNEL and pro
      caspase3 expression assay showed a significant increase in apoptosis after
      combined treatment with adriamycin and siRNA targeting survivin. Our results
      demonstrate that survivin is downregulated by p53, and that siRNA targeting of
      survivin increases cell sensitivity to adriamycin and promotes apoptosis. siRNA
      targeting of survivin could be potentially useful for increasing sensitivity to
      anticancer drugs, especially in drug-resistant cells with mutated p53.

PMID- 16108014
TI  - Nucleophile selectivity in the acyl transfer reaction of a designed enzyme.
AB  - The acyl transfer reaction of S-glutathionyl benzoate (GSB) is catalyzed by a
      rationally designed mutant of human glutathione transferase A1-1, A216H. The
      catalyzed reaction proceeds via the formation of an acyl intermediate and has
      been studied in the presence of nitrogen, oxygen, and sulfur nucleophiles to
      determine the selectivity with regards to nucleophile structure. Methanol was
      previously shown to react with the acyl intermediate and form the corresponding
      ester, methylbenzoate, under a significant rate enhancement. In the present
      investigation, the dependence on nucleophile structure and reactivity has been
      investigated. Ethane thiol gave rise to a larger rate enhancement in the enzyme
      catalyzed reaction than ethanol, whereas ethylamine did not increase the reaction
      rate. The reactivities toward the acyl intermediate of primary and secondary
      alcohols with similar pKa values depended on the structure of the aliphatic
      chain, and 1-propanol was the most efficient alcohol. The reactivity of the
      oxygen nucleophiles was also found to depend strongly on pKa as 2,2,2
      trifluoroethanol, with a pKa of 12.4, was the most efficient nucleophile of all
      that were tested. Saturation kinetics was observed in the case of 1-propanol,
      indicating a second binding site in the active site of A216H. The nucleophile
      selectivity of A216H provides the knowledge base needed for the further
      reengineering of A216H towards alternative substrate specificities.

PMID- 16108015
TI  - A tumor vaccine containing anti-CD3 and anti-CD28 bispecific antibodies triggers
      strong and durable antitumor activity in human lymphocytes.
AB  - We recently reported on newly designed virus-targeted bispecific CD3- and CD28
      binding molecules for human T-cell activation. When bound via one arm to a human
      virus-modified tumor cell vaccine, these reagents caused a polyclonal T-cell
      response and overcame the potential various T-cell evasion mechanisms of tumor
      cells. In our current study, we demonstrated the induction of strong antitumor
      activity in human lymphocytes upon coincubation with a virus-modified tumor
      vaccine containing anti-CD3 and anti-CD28 bispecific antibodies. Blood
      mononuclear cells or purified T cells that were coincubated with such a tumor
      vaccine for 3 days were able to destroy monolayers of human breast carcinoma and
      other carcinoma cells. Serial transfer to new tumor cell monolayers revealed
      antitumor cytotoxic activity in such effector cells that lasted for about 10
      days. Nontumor target cells appeared to be much less sensitive to the activated
      effector cells. Although the bispecific molecules alone did not activate effector
      cells, their binding to virus-infected tumor cells was important and more
      effective than their binding to free virus. Antitumor activity of the activated
      effector cells was mediated through soluble factors as well as through direct
      cell contact of effector cells with the nontargeted bystander tumor cells. Since
      the virus-modified tumor vaccine is well tolerated and already exhibits a certain
      effectiveness in cancer patients, the combination with new bispecific molecules
      has the potential to introduce additional antitumor effects. The reagents can
      also be combined with Newcastle Disease Virus (NDV)-based oncolytic virotherapy.

PMID- 16108016
TI  - Cytotoxic effects induced by a combination of cyclopamine and gefitinib, the
      selective hedgehog and epidermal growth factor receptor signaling inhibitors, in
      prostate cancer cells.
AB  - Although the blockade of the hedgehog cascade by using cyclopamine has been
      reported to inhibit the growth of some cancer cell types, few studies on the
      mechanism by which this drug alone or in combination with other cytotoxic agents
      induces its cytotoxic effect have been reported. In our study, we evaluate, for
      the first time, the antiproliferative and cytotoxic effects induced by a
      combination of selective SMO inhibitor, cyclopamine and epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitor, gefitinib on metastatic prostate
      cancer (PC) cells. The results revealed that cyclopamine, alone or at a lower
      concentration in combination with gefitinib, inhibited the growth of sonic
      hedgehog- (SHH), epidermal growth factor- (EGF) and serum-stimulated androgen
      sensitive LNCaP-C33 and LNCaP-LN3 and androgen-independent LNCaP-C81, DU145 and
      PC3 cells. The antiproliferative effect of cyclopamine and gefitinib, alone or in
      combination, was mediated via a blockade of the PC3 cells in the G1 phase of the
      cell cycle. Importantly, the combined cyclopamine and gefitinib also caused a
      higher rate of apoptotic death of PC cells compared to single agents. The
      cytotoxic effect induced by these drugs in PC3 cells appears to be mediated at
      least, in part, via the mitochondrial pathway through the depolarization of the
      mitochondrial membrane and the release of cytochrome c and reactive oxygen
      species into the cytosol. This was also accompanied by the activation of caspase
      cascades, PARP cleavage and DNA fragmentation. Additionally, the combined
      cyclopamine and gefitinib were more effective at suppressing the invasiveness of
      PC3 cells through matrigel in vitro as the drugs alone. These findings indicate
      that the simultaneous blockade of SHH-GLI-1 and EGF-EGFR signaling, which results
      in the growth arrest and massive rate of apoptotic cell death, represents a
      promising strategy for a more effective treatment of metastatic PC forms.

PMID- 16108017
TI  - Method for multimodal analysis of independent source differences in
      schizophrenia: combining gray matter structural and auditory oddball functional
      data.
AB  - The acquisition of both structural MRI (sMRI) and functional MRI (fMRI) data for
      a given study is a very common practice. However, these data are typically
      examined in separate analyses, rather than in a combined model. We propose a
      novel methodology to perform independent component analysis across image
      modalities, specifically, gray matter images and fMRI activation images as well
      as a joint histogram visualization technique. Joint independent component
      analysis (jICA) is used to decompose a matrix with a given row consisting of an
      fMRI activation image resulting from auditory oddball target stimuli and an sMRI
      gray matter segmentation image, collected from the same individual. We analyzed
      data collected on a group of schizophrenia patients and healthy controls using
      the jICA approach. Spatially independent joint-components are estimated and
      resulting components were further analyzed only if they showed a significant
      difference between patients and controls. The main finding was that group
      differences in bilateral parietal and frontal as well as posterior temporal
      regions in gray matter were associated with bilateral temporal regions activated
      by the auditory oddball target stimuli. A finding of less patient gray matter and
      less hemodynamic activity for target detection in these bilateral anterior
      temporal lobe regions was consistent with previous work. An unexpected corollary
      to this finding was that, in the regions showing the largest group differences,
      gray matter concentrations were larger in patients vs. controls, suggesting that
      more gray matter may be related to less functional connectivity in the auditory
      oddball fMRI task.

PMID- 16108018
TI  - Sources of cortical rhythms in adults during physiological aging: a multicentric
      EEG study.
AB  - This electroencephalographic (EEG) study tested whether cortical EEG rhythms
      (especially delta and alpha) show a progressive increasing or decreasing trend
      across physiological aging. To this aim, we analyzed the type of correlation
      (linear and nonlinear) between cortical EEG rhythms and age. Resting eyes-closed
      EEG data were recorded in 108 young (Nyoung; age range: 18-50 years, mean age
      27.3+/-7.3 SD) and 107 elderly (Nold; age range: 51-85 years, mean age 67.3+/-9.2
      SD) subjects. The EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz),
      alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30
      Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic
      tomography (LORETA). Statistical results showed that delta sources in the
      occipital area had significantly less magnitude in Nold compared to Nyoung
      subjects. Similarly, alpha 1 and alpha 2 sources in the parietal, occipital,
      temporal, and limbic areas had significantly less magnitude in Nold compared to
      Nyoung subjects. These nine EEG sources were given as input for evaluating the
      type (linear, exponential, logarithmic, and power) of correlation with age. When
      subjects were considered as a single group there was a significant linear
      correlation of age with the magnitude of delta sources in the occipital area and
      of alpha 1 sources in occipital and limbic areas. The same was true for alpha 2
      sources in the parietal, occipital, temporal, and limbic areas. In general, the
      EEG sources showing significant linear correlation with age also supported a
      nonlinear correlation with age. These results suggest that the occipital delta
      and posterior cortical alpha rhythms decrease in magnitude during physiological
      aging with both linear and nonlinear trends. In conclusion, this new
      methodological approach holds promise for the prediction of dementia in mild
      cognitive impairment by regional source rather than surface EEG data and by both
      linear and nonlinear predictors.

PMID- 16108019
TI  - Motion standstill leads to activation of inferior parietal lobe.
AB  - Previous studies on motion perception revealed motion-processing brain areas
      sensitive to changes in luminance and texture (low-level) and changes in salience
      (high-level). The present functional magnetic resonance imaging (fMRI) study
      focused on motion standstill. This phenomenon, occurring at fast presentation
      frequencies of visual moving objects that are perceived as static, has not been
      previously explored by neuroimaging techniques. Thirteen subjects were
      investigated while perceiving apparent motion at 4 Hz, at 30 Hz (motion
      standstill), isoluminant static and flickering stimuli, fixation cross, and blank
      screen, presented randomly and balanced for rapid event-related fMRI design.
      Blood oxygenation level-dependent (BOLD) signal in the occipito-temporal brain
      region MT/V5 increased during apparent motion perception. Here we could
      demonstrate that brain areas like the posterior part of the right inferior
      parietal lobule (IPL) demonstrated higher BOLD-signal during motion standstill.
      These findings suggest that the activation of higher-order motion areas is
      elicited by apparent motion at high presentation rates (motion standstill). We
      interpret this observation as a manifestation of an orienting reaction in IPL
      towards stimulus motion that might be detected but not resolved by other motion
      processing areas (i.e., MT/V5).

PMID- 16108020
TI  - Homocysteine and serum markers of immune activation in primary dystonia.
AB  - The cause of primary dystonia remains unknown. Several reports point to immune
      system disturbances in primary dystonia and a recent study demonstrated
      hyperhomocysteinemia in cervical dystonia. Homocysteine (HCY) is an amino acid
      and elevated HCY concentrations were shown to be associated with immune system
      activation and increased neopterin serum concentrations. We examined HCY serum
      concentrations together with serum markers of immune activation in patients with
      different types of primary dystonia. Eighty-three patients with different types
      of primary dystonia were included and investigated at least 3 months following
      botulinum toxin treatment. Thirty-six healthy volunteers with similar age and sex
      distribution served as controls. Total serum HCY, kynurenine, and tryptophan
      concentrations were determined by high-performance liquid chromatography;
      neopterin, folate, and vitamin B12 concentrations were measured by immunoassays.
      Routine blood analysis, including C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), and white blood count (WBC), was performed. Patients
      with primary dystonia had significantly higher HCY concentrations compared to
      controls. Among the dystonia subtypes, no significant difference of HCY serum
      concentrations was observed. CRP and ESR were within the normal range in >90% of
      the patients and all had normal WBC. Neopterin, kynurenine, and tryptophan serum
      concentrations were similar in patients and controls and not correlated with HCY
      serum concentrations. The results provide evidence against enhanced cellular
      immune activation in patients with primary dystonia. However,
      hyperhomocysteinemia was present in all dystonia subtypes and unrelated to immune
      activation in this study. HCY is a neuronal excitotoxic amino acid and
      hyperhomocysteinemia is considered an independent vascular risk factor. Further
      studies are required to define the background of hyperhomocysteinemia in primary
      dystonia.

PMID- 16108021
TI  - In vivo imaging of microglial activation with [11C](R)-PK11195 PET in progressive
      supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a neurodegenerative disease presenting
      with voluntary gaze difficulties, early falls, and Parkinsonism. Neuronal loss,
      associated with intracellular neurofibrillary tangles and activated microglia, is
      found targeting the basal ganglia, brainstem nuclei, and frontal cortex. [11C](R)
      PK11195 PET is a marker of peripheral benzodiazepine binding sites (PBBS)
      expressed by activated microglia. We have used [11C](R)-PK11195 PET to
      demonstrate in vivo the degree and distribution of the glial response to the
      degenerative process in four patients with PSP. Compared to normal age-matched
      controls, the PSP patient group showed significantly increased mean [11C](R)
      PK11195 binding in the basal ganglia, midbrain, the frontal lobe, and the
      cerebellum. Two of the patients were rescanned after 6 to 10 months and during
      that time the level of microglial activation remained stable. [11C](R)-PK11195
      PET reveals a pattern of increased microglial activation in PSP patients
      involving cortical and subcortical regions that corresponds well with the known
      distribution of neuropathological changes. [11C](R)-PK11195 PET, therefore, may
      help in characterizing in vivo the underlying disease activity in PSP.

PMID- 16108022
TI  - Staged bilateral stereotactic pallidothalamotomy for life-threatening dystonia in
      a child with Hallervorden-Spatz disease.
AB  - Hallervorden-Spatz disease (HSD) is a rare disorder characterized by progressive
      motor dysfunction and dementia. Dystonia is the most prominent and disabling
      symptom, responding only to a modest extent to pharmacological therapy. At the
      moment, only a few cases have been reported to improve dystonia and even fewer to
      resolve status dystonicus for a longer period in children. The authors present
      the case of a 10-year-old boy who had progressive generalized dystonia, resulting
      in spontaneous femur fracture and life-threatening swallowing and respiratory
      disability. As a rescue solution, staged bilateral pallidothalamotomy was
      performed. Postoperatively, Burke-Fahn-Marsden Dystonia Rating Scale and Dystonia
      Disability Rating Scale improved (from 116 and 30 points to 41 and 18 points,
      respectively) and painful dystonia was resolved, which was still continuous 4
      years later (47 and 20 points). Stereotactic staged bilateral pallidothalamotomy
      should be considered as a potential treatment in the management of life
      threatening generalized dystonia related to HSD.

PMID- 16108023
TI  - Alteration of central motor excitability in a patient with hemimasticatory spasm
      after treatment with botulinum toxin injections.
AB  - Hemimasticatory spasm (HMS) is a condition characterized by paroxysmal
      involuntary contraction of masticatory muscles. We performed an
      electrophysiological investigation of a single patient with HMS to identify any
      pathophysiological changes associated with the condition. We identified a delayed
      M wave and jaw jerk on the affected side and an absent masseteric silent period
      during spasm. Botulinum toxin injections successfully treated the clinical
      symptoms and resulted in a significant reduction in the excitability of the blink
      reflex recovery cycle. These data suggest that HMS may be due to ectopic activity
      in the motor portion of the trigeminal nerve that is capable of inducing changes
      in the excitability of central reflex pathways. These changes can be altered by
      successful treatment with botulinum toxin.

PMID- 16108024
TI  - Dystonia gravidarum: a new entity?
AB  - We describe cervical dystonia occurring in a 31-year-old, previously well,
      primigravid, primiparous Chinese woman at 4 weeks' amenorrhea, which was
      ameliorated with low-dose clonazepam and disappeared completely by the end of the
      second trimester without recurring despite her being tapered off benzodiazepine
      therapy. Investigations were unremarkable for structural and biochemical causes
      of dystonia. Chorea, paraballismus, and restless legs syndrome are known to occur
      during pregnancy, attributable to high estrogen levels. Dystonia, on the other
      hand, has not been described to occur de novo in pregnancy. This association
      should be considered in women of reproductive age who present with cervical
      dystonia.

PMID- 16108025
TI  - Rating scale for psychogenic movement disorders: scale development and
      clinimetric testing.
AB  - We developed and tested the clinimetric properties of a scale for psychogenic
      movement disorders (PMDs). PMDs are disabling but lack any generally accepted
      treatment strategies. To develop treatments, means of assessing disease severity
      must be provided. No scale to assess PMDs existed. The PMD scale developed here
      rates 10 phenomena (rest tremor, action tremor, dystonia, chorea, bradykinesia,
      myoclonus, tics, athetosis, ballism, cerebellar incoordination), 2 functions
      (gait, speech), and 14 body regions. To study interrater agreement, three
      movement disorder neurologists independently rated 88 videotapes of PMD patients.
      Data analysis was performed using a kappa coefficient of agreement, Kendall's
      coefficient of concordance, Spearman correlations, and intraclass correlation
      coefficients. Validity and scale responsiveness were tested as well. All
      phenomena and speech and gait dysfunction occurred in the patient sample. A wide
      range of affected body regions, severity, and incapacitation was captured.
      Ratings showed excellent interrater reliability for presence or absence of each
      phenomenon (kappa range, 0.63 to 0.86). Kendall's concordance coefficients for
      phenomenology, function, and total PMD scores were 0.92, 0.93, and 0.91. Spearman
      correlations between raters ranged from 0.86 to 0.90. The scale was responsive to
      changes that occurred as a result of a neuropsychiatric intervention. The PMD
      scale adequately captures the complex movements of PMDs and can be used to assess
      PMDs and test the efficacy of intervention strategies.

PMID- 16108026
TI  - Myoclonus of the scapula after acute long thoracic nerve lesion: a case report.
AB  - We describe a patient who presented myoclonus in the left scapula 3 months after
      a traumatic lesion of the left long thoracic nerve. Myoclonic activity was
      recorded as pseudorhythmic electromyographic bursts repeated at a frequency of 2
      to 4 Hz, each lasting between 100 and 200 msec, in the left serratus-dorsalis
      muscle region, trapezius, and deltoid muscles. A combination of peripheral and
      central mechanisms may have induced the myoclonus in this case.

PMID- 16108027
TI  - A GPIIb/IIIa bioreactor for specific treatment of immune thrombocytopenic
      purpura, an autoimmune disease. Preparation, in vitro characterization, and
      preliminary proof-of-concept animal studies.
AB  - Immune thrombocytopenic purpura (ITP) is an autoimmune disease that affects
      thousands of Americans each year. The resulting thrombocytopenia, which develops
      from destruction of platelets (PLT) by anti-PLT autoantibodies (APAb), is often
      associated with hemorrhagic complications. Existing therapies are not effective
      and are associated with significant morbidity. Recently, a new treatment modality
      using plasmapheresis with a Protein-A column has shown some clinical promise.
      Yet, although this method would remove the pathogenic APAb, it would also deplete
      protective antibodies, thereby weakening the body's self-defense system. Because
      about 80% of patients with ITP develop APAb against the GPIIb/IIIa antigens on
      PLT, a novel approach of attaching a GPIIb/IIIa-linked bioreactor with an
      extracorporeal circuit is suggested herein to achieve highly effective/specific
      APAb removal and overcome shortcomings of plasmapheresis in treating ITP. A
      hollow fiber-based bioreactor device was fabricated, and GPIIb/IIIa antigens were
      immobilized onto the inner lumens of the hollow fibers by using the
      epichlorohydrin activation method. An optimized bioreactor containing a loading
      of 1.63 mg GPIIb/IIIa/g fibers and adsorption capacity of 1.9 mg 7E3/g fibers was
      developed. Preliminary proof-of-concept investigation using a 7E3-induced
      thrombocytopenic rat model (which mimicked clinical ITP) was carried out. A
      complete (100%) return of PLT counts to their initial levels was observed in rats
      within 6 h after the GPIIb/IIIa bioreactor treatment. In addition, a rapid
      restoration of WBC counts in the treated rats was also found. These preliminary
      findings shed light of promise of using the GPIIb/IIIa bioreactor approach in
      achieving highly improved ITP therapy.

PMID- 16108028
TI  - Place-related neural responses in the monkey hippocampal formation in a virtual
      space.
AB  - Place cells in the rodent hippocampal formation (HF) are suggested to be the
      neural substrate for a spatial cognitive map. This specific spatial property of
      the place cells are regulated by both allothetic cues (i.e., intramaze local and
      distal cues) as well as idiothetic sensory inputs; the context signaled by the
      distal cues allows local and idiothetic cues to be employed for spatial tuning
      within the maze. To investigate the effects of distal cues on place-related
      activity of primate HF neurons, 228 neurons were recorded from the monkey HF
      during virtual navigation in a similar situation to a rodent water maze, in which
      distal cues were important to locate the animal's position. A subset of 72
      neurons displayed place-related activity in one or more virtual spaces. Most
      place-related responses disappeared or changed their spatial tuning (i.e.,
      remapping) when the arrangements of the distal cues were altered/moved in the
      virtual spaces. These specific features of the monkey HF might underlie
      neurophysiological bases of human episodic memory.

PMID- 16108029
TI  - Deep brain stimulation to treat hyperkinetic symptoms of Cockayne syndrome.
AB  - Cockayne syndrome manifests a spectrum of neurological dysfunction that includes
      medically intractable movement disorders. Deep brain stimulation has not been
      well studied in such rare neurodegenerative conditions. In this case, stimulation
      of the ventral intermediate nucleus of the thalamus was used to manage severe
      motor symptoms in a young man with Cockayne syndrome. There was a marked and
      progressive response to thalamic stimulation within weeks of surgery. These
      results suggest that patients with Cockayne syndrome should be considered for
      deep brain stimulation to treat refractory movement disorders.

PMID- 16108030
TI  - Use of complementary therapies in patients with Parkinson's disease in Singapore.
AB  - To determine the frequency and spectrum of complementary therapy (CT) use and its
      association with sociodemographic or disease-specific characteristics among Asian
      patients with Parkinson's disease (PD) in Singapore, we interviewed 159 patients
      using a structured questionnaire. Sixty-one percent (95% CI=55-67) of
      participants used at least one type of CT for PD, of which the most common were
      traditional medicine, acupuncture, and vitamins/health supplements. Among CT
      users, 40% (95% CI=32-48) subjectively reported some improvement of their
      symptoms. However, only 16% informed their physicians of their use of CT. Due to
      unequal follow-up times, a survival analysis approach was adopted for statistical
      analysis. The rate of starting CT use was 1.2/100 person months. At 3 years after
      PD diagnosis, 48% had started using CT. Among a subgroup of participants, those
      with a baseline Unified Parkinson's Disease Rating Scale motor score of more than
      16 were 2.5 times more likely to use CT compared to those with a baseline score
      of 16 or less (P=0.031; 95% CI=1.1-5.8). CT use was not associated with age of
      onset of PD or other sociodemographic factors. The use of CT is high among Asian
      PD patients. Patients with more severe motor dysfunction at onset are more likely
      to use CT.

PMID- 16108031
TI  - Transplantation of chondrocytes seeded on collagen-based scaffold in cartilage
      defects in rabbits.
AB  - Recent success in tissue engineering by restoring cartilage defects by
      transplanting autologous chondrocyte cells on a three-dimensional scaffold has
      prompted the improvement of this therapeutic strategy. Here we describe a new
      approach investigating the healing of rabbit cartilage by means of autologous
      chondrocytes seeded on a biomaterial made of an equine collagen type I-based
      scaffold. Full-thickness defects were created bilaterally in the weight-bearing
      surface of the medial femoral condyle of both femora of New Zealand male rabbits.
      The wounds were then repaired by using both chondrocytes seeded on the
      biomaterial and biomaterial alone. Controls were similarly treated but received
      either no treatment or implants of the delivery substance. Histological
      examination of the reconstructed tissues at 1, 3, 6, and 12 months after
      transplantation showed that at 1 and 3 months there was no formation of
      reconstructed tissue in any of the groups evaluated; after 6 months there was
      evidence of a newly regenerated tissue with some fibrocartilaginous features only
      in the group treated with biomaterial-seeded cells, and at 12 months a more
      organized tissue was evident in the same group. With regards to the group
      transplanted with biomaterial alone and the untreated control group, there was no
      evidence of new tissue production. These results advocate the use of this
      collagen-based scaffold for further in vivo studies on large size animals and,
      finally, in human clinical trials for the treatment of knee cartilage defects.

PMID- 16108032
TI  - Inefficient proteasomal-degradation pathway stabilizes AP-2alpha and activates
      HER-2/neu gene in breast cancer.
AB  - HER-2/neu proto-oncogene is overexpressed in about one fourth of human breast
      cancers. AP-2 transcription factors bind to the HER-2/neu gene promoter and
      activate its expression. In a striking concurrence, anomalous abundance of AP
      2alpha protein or its homolog AP-2gamma is also detected with HER-2/neu protein
      in mammary tumor-derived cell lines. This suggests that the deregulation of AP-2
      is the preceding pathogenic event and probably the pivotal one in this type of
      mammary carcinogenesis. We examined the process of AP-2alpha gene expression in
      mammary carcinoma cell lines to identify where the aberration had occurred. We
      found no amplification of the AP-2alpha gene. Its promoter was marginally
      upregulated; however, it did not significantly increase the mRNA levels. When the
      AP-2alpha protein was examined, a remarkable stability was seen in breast cancer
      cell lines MDA-MB-453 and SK-BR-3, with a half-life of over 30 hr. This is
      sharply higher than the approximate 1 hr observed in mammary epithelial cell line
      MCF-10A and murine cell line NIH 3T3. Treatment of MCF-10A and NIH 3T3 cells with
      the proteasome inhibitor MG-132 showed that AP-2alpha was ubiquitinated and its
      level significantly increased. Moreover, this increase was accompanied by
      elevated levels HER-2/neu protein. In contrast, weaker ubiquitination of AP
      2alpha was seen in MDA-MB-453 and SK-BR-3 cancer cells, and MG-132 treatment did
      not raise the AP-2alpha level any further. These results uncover that unusual
      stability is the main mechanism that raises the levels of AP-2 proteins, and in
      addition, provide the first clue that defective ubiquitin-dependent proteasomal
      degradation pathway is possibly the prime cause that affects the HER-2/neu gene
      and culminates in breast cancer.

PMID- 16108033
TI  - Role of interleukin-18 and its receptor in hepatocellular carcinoma associated
      with hepatitis C virus infection.
AB  - Interleukin (IL)-18 is a proinflammatory cytokine that is up-regulated in
      patients with hepatitis C virus (HCV) infection, which is the most common
      underlying disease in hepatocellular carcinoma (HCC). The purpose of our study
      was to investigate the role of IL-18 in HCC associated with HCV infection. Sixty
      five patients with HCC and HCV infections who received curative surgical
      resections were examined in our study. The expression of the IL-18 receptor was
      investigated in HCC tissues obtained from these patients and in 2 HCC cell lines.
      Nuclear factor (NF)-kappaB activity and the expression of Bcl-xL and xIAP mRNA
      were tested in the cell lines using recombinant human (rh) IL-18. The IL-18
      receptor was expressed in both the HCC tissues and the cell lines. NF-kappaB
      activation and the expression of Bcl-xL and xIAP mRNA were increased by rhIL-18.
      Moreover, rhIL-18 suppressed the apoptosis of HCC cells which was induced by
      etoposide in vitro. The overall survival rate (55.4%) was significantly worse in
      the IL-18 receptor-positive patients than in the IL-18 receptor-negative patients
      (p = 0.015). In a Cox multivariate analysis, the expression of the IL-18 receptor
      was found to be a significant predictor of a poor outcome in HCC patients. The
      expression of the IL-18 receptor and an antiapoptotic mechanism involving NF
      kappaB activation in HCC cells may be implicated in a poor patient outcome.

PMID- 16108034
TI  - Human fibroblast reactions to standard and electropolished titanium and Ti-6Al
      7Nb, and electropolished stainless steel.
AB  - Stainless steel (SS), titanium (cpTi), and Ti-6Al-7Nb (TAN) are frequently used
      metals in orthopedic internal fracture fixation. Although reactivity to SS and
      cpTi are noted in reference, the soft tissue compatibility of TAN has not been
      comprehensively studied. This study focuses on the in vitro soft tissue
      compatibility of TAN in comparison to SS and cpTi using a human fibroblast model.
      The industrial standard surface finishes of these three materials vary
      considerably in view of their use in similar applications. To distinguish between
      material parameters of topography and chemistry, we have included electropolished
      (e.p) counterparts of the standard preparations of cpTi and TAN in the study
      (standard SS is e.p). All materials were characterized using atomic force
      microscopy, profilometry, and scanning electron microscopy. Our findings
      demonstrate that cell morphology and growth rate was similar for SS, and e.p.
      cpTi and TAN, with cells well spread and forming a confluent monolayer by 10
      days. Cell growth on standard cpTi was similar to the electropolished samples;
      however, they showed a less spread morphology with more filopodia and surface
      ruffling present. Cell morphology on standard TAN was rounded or elongated and
      proliferation was inhibited at all time points, with possible cell necrosis by
      day 10. We found evidence of endocytosis of beta-phase particles originating from
      the standard TAN surface. We believe that the particle uptake coupled with the
      characteristic surface topography contribute to the noncytocompatibility of
      fibroblasts on standard TAN.

PMID- 16108035
TI  - Wnt pathway is involved in pleomorphic adenomas induced by overexpression of
      PLAG1 in transgenic mice.
AB  - Pleomorphic adenoma gene 1 (PLAG1) was found frequently rearranged and activated
      in human salivary gland pleomorphic adenomas. It encodes a developmentally
      regulated transcription factor. Ectopic overexpression of PLAG1 has been proposed
      to play a crucial role in tumorigenesis of salivary gland pleomorphic adenomas.
      It was reported that PLAG1 can activate the transcription of insulin-like growth
      factor 2 (IGF2), functioning as a protooncogene. In this report, we show that the
      salivary gland tumors developed in PLAG1 transgenic mice share major
      histopathologic features with human pleomorphic adenomas. It was found that beta
      catenin, the key component of Wnt signaling pathway, was upregulated at
      transcriptional level in tumors developed in 3 independent transgenic mouse
      lines. Immunohistochemical staining revealed that expression of beta-catenin as
      well as c-myc, downstream of beta-catenin in Wnt signaling pathway, was highly
      upregulated with overexpression of PLAG1 transgene in tumor and normal transgenic
      salivary gland tissues. Moreover, we found that PLAG1 can activate the
      transcription of mouse but not human beta-catenin in the 3T3 cells cotransfected
      with reporter constructs. Sequence analysis shows there are 4 PLAG1 consensus
      binding sites in mouse beta-catenin promoter region but not in human. Our
      findings provide the first in vivo evidence for the oncogenic activity of PLAG1
      in pleomorphic adenoma tumorigenesis, reveal a valued animal model for human
      salivary gland tumors and suggest that Wnt signaling pathway may also contribute
      to the development of pleomorphic adenomas in transgenic mice.

PMID- 16108036
TI  - A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch
      in spontaneous bacterial peritonitis.
AB  - The administration of albumin improves circulatory function, prevents hepatorenal
      syndrome, and reduces hospital mortality in patients with cirrhosis and
      spontaneous bacterial peritonitis. This randomized unblinded pilot study compared
      the effect of albumin (10 patients) and the synthetic plasma expander
      hydroxyethyl starch 200/0.5 (10 patients) on the systemic hemodynamics of
      patients with spontaneous bacterial peritonitis. Baseline measurements were
      performed within 12 hours after diagnosis of infection. Patients then received 2
      doses of the volume expander (1.5 g/kg body weight after baseline measurements
      and 1 g/kg body weight on day 3). Measurements were repeated after infection
      resolution. Treatment with albumin was associated with a significant increase in
      arterial pressure and a suppression of plasma renin activity, indicating an
      improvement in circulatory function. This occurred in the setting of a
      significant expansion of central blood volume (increase in cardiopulmonary
      pressures and atrial natriuretic factor) and an increase in systolic volume and
      systemic vascular resistance. In contrast, no significant changes were observed
      in these parameters in patients treated with hydroxyethyl starch. Von Willebrand
      related antigen plasma levels significantly decreased in patients treated with
      albumin but not in those treated with hydroxyethyl starch. Serum nitrates and
      nitrites increased in patients treated with hydroxyethyl starch but not in those
      treated with albumin. These data suggest an effect of albumin on endothelial
      function. In conclusion, albumin but not hydroxyethyl starch improves systemic
      hemodynamics in patients with spontaneous bacterial peritonitis. This effect is
      due not only to volume expansion but also to an action on the peripheral arterial
      circulation.

PMID- 16108038
TI  - Expression of dentin sialophosphoprotein in human prostate cancer and its
      correlation with tumor aggressiveness.
AB  - Recent studies have demonstrated that two SIBLING family members, bone
      sialoprotein (BSP) and osteopontin (OPN), are overexpressed in human prostate
      cancer. The expression of these proteins is associated with the acquisition of a
      metastatic phenotype by cancer cells and a poor prognosis for the patient. Dentin
      sialophosphoprotein (DSPP) shares several structural and genetic features with
      OPN and BSP. The presence of DSPP has been recently established in salivary
      glands, indicating that its expression is not restricted to mineralized tissues.
      However, its potential expression in human tumors has not been addressed yet. In
      this study, we sought to evaluate the expression of DSPP in human prostate
      cancer. Immunohistochemistry was performed on 69 prostate cancer specimens using
      LFMb-21 anti-DSPP monoclonal antibody. All of the prostate cancer lesions
      examined expressed detectable levels of DSPP, as compared with no or low level of
      expression in adjacent normal glands (p < 0.0001). High grade prostatic
      intraepithelial neoplasia (HGPIN) glands generally displayed DSPP expression
      levels that were similar to those found in neighboring cancer glands. DSPP
      expression was significantly associated with the pathological stage (p = 0.0087)
      and the Gleason score (p = 0.0176) of the tumors. Western Blot was performed on 5
      representative prostate tumor extracts and 3 prostatic tumor cell lines (PC3,
      LNCaP and DU145). All tumor extracts and cell lines analyzed have been found to
      express DSPP. In addition, in situ hybridization was used to assess the presence
      of DSPP mRNA. DSPP was detected at the RNA level in both HGPIN and tumoral
      glands. This study shows for the first time that DSPP is ectopically expressed in
      human prostate cancer. The expression of this SIBLING protein strongly correlates
      with conventional histopathological prognostic indicators of prostate cancer
      progression.

PMID- 16108039
TI  - Tissue transglutaminase (TG2) acting as G protein protects hepatocytes against
      Fas-mediated cell death in mice.
AB  - Tissue transglutaminase (TG2) is a protein cross-linking enzyme known to be
      expressed by hepatocytes and to be induced during the in vivo hepatic apoptosis
      program. TG2 is also a G protein that mediates intracellular signaling by the
      alpha-1b-adrenergic receptor (AR) in liver cells. Fas/Fas ligand interaction
      plays a crucial role in various liver diseases, and administration of agonistic
      anti-Fas antibodies to mice causes both disseminated endothelial cell apoptosis
      and fulminant hepatic failure. Here we report that an intraperitoneal dose of
      anti-Fas antibodies, which is sublethal for wild-type mice, kills all the TG2
      knock-out mice within 20 hours. Although TG2-/- thymocytes exposed to anti-Fas
      antibodies die at the same rate as wild-type mice, TG2-/- hepatocytes show
      increased sensitivity toward anti-Fas treatment both in vivo and in vitro, with
      no change in their cell surface expression of Fas, levels of FLIP(L) (FLICE
      inhibitory protein), or the rate of I-kappaBalpha degradation, but a decrease in
      the Bcl-xL expression. We provide evidence that this is the consequence of the
      impaired AR signaling that normally regulates the levels of Bcl-xL in the liver.
      In conclusion, our data suggest the involvement of adrenergic signaling pathways
      in the hepatic regeneration program, in which Fas ligand-induced hepatocyte
      proliferation with a simultaneous inhibition of the Fas-death pathway plays a
      determinant role.

PMID- 16108040
TI  - Small gallstones and pancreatitis.

PMID- 16108041
TI  - Effects of an infrared pulsed laser device (IPLD) over apoptosis in cancer cells.

PMID- 16108042
TI  - Effects of neck exposure to 5.5 mT static magnetic field on pharmacologically
      modulated blood pressure in conscious rabbits.
AB  - Static magnetic fields (SMF) in the millitesla (mT) range have been reported to
      modulate microcirculatory hemodynamics and/or blood pressure (BP) under
      pharmacologically modified state in mammals. This study was designed to
      investigate the acute effects of local application of a SMF to neck or pelvic
      region under pharmacologically modulated BP; norepinephrine (NE)-induced
      hypertension as well as an L-type voltage-gated Ca(2+) channel blocker,
      nicardipine (NIC)-induced hypotension in conscious rabbits. Magnetic flux
      densities were up to 5.5 mT and the spatial magnetic gradient peaked in neck
      (carotid sinus baroreceptor) region at the level of approximately 0.06 mT/mm. The
      duration of exposure was 30 min (including 10 min of pretreatment) and the
      effects on BP were investigated up to 100 min postexposure. Baroreflex
      sensitivity (BRS) was estimated from invasive recordings of systolic BP and pulse
      interval. Neck exposure to 5.5 mT significantly attenuated the pharmacologically
      induced vasoconstriction or vasodilation, and subsequently suppressed the
      increase or decrease in BP compared with sham exposure. In contrast, pelvic
      exposure to 5.5 mT did not significantly antagonized NE-elevated BP or NIC
      reduced BP. The neck exposure to 5.5 mT has a biphasic and restorative effect on
      vascular tone and BP acting to normalize the tone and BP. The neck exposure to
      5.5 mT caused a significant increase in BRS in NE-elevated BP compared with sham
      exposure. The buffering effects of the SMF on increased hemodynamic variability
      under NE-induced high vascular tone and NIC-induced low vascular tone might be,
      in part, dependent on baroreflex pathways, which could modulate NE-mediated
      response in conjunction with Ca(2+) dynamics.

PMID- 16108043
TI  - Study of subgridding in SAR computation for the cochlea.
AB  - A 3D subgridding technique is used to model the specific absorption rate (SAR)
      distribution in the isolated cochlea exposed to mobile phone radiation at 1750
      MHz using the FDTD method. The cochlea is modeled using an increasing spatial
      resolutions of 1, 1/3, 1/5, and 1/7 mm. First simulations were performed at 1 mm
      spatial resolution. The numerical resolution was then increased to 1/3, 1/5, and
      1/7 using subgridding without changing the spatial resolution. A second set of
      simulations was then performed when both the spatial and numerical resolution
      were increased together. From the obtained results, we conclude that subgridding
      is important only when both the numerical resolution of the computational grid
      and the spatial resolution of the model are increased together.

PMID- 16108044
TI  - Characterization of polymeric poly(epsilon-caprolactone) injectable implant
      delivery system for the controlled delivery of contraceptive steroids.
AB  - Contraceptive steroids levonorgestrel (LNG) and ethinyl estradiol (EE) have been
      encapsulated with poly(epsilon-caprolactone) (PCL) microspheres using a w / o /w
      double emulsion method. The microspheres prepared were smooth and spherical, with
      a mean size from 8-25 microm. In vitro release profiles of microspheres showed a
      trend of increasing initially at the first week, and thereafter the release was
      sustained. At the end of the seventh week LNG/EE from 1:5 and 1:10 PCL
      microspheres were 60 and 48%, 52 and 46%, respectively. An in vitro degradation
      study shows that at the 20th week the microspheres maintained the surface
      integrity. The PCL microspheres showed a triphasic in vivo release profile with
      an initial burst effect due to the release of the steroid adsorbed on the
      microsphere surface, a second sustained release phase due to the steroid
      diffusion through the pores or channels formed in the polymer matrix, and third
      phase due to polymer bioerodible. Histological examination of PCL microspheres
      injected intramuscularly into thigh muscle of a rat showed a minimal inflammatory
      reaction demonstrating that contraceptive steroid-loaded microspheres were
      biocompatible. The level of inflammatory cytokines determined by immunostaining
      for IL-1alpha, the tissue response to formulations at the first week was
      considered mild, whereas at the end of the 20th week the inflammatory response
      ceased. Thus, this study helped us to evaluate the feasibility of using these
      microspheres as a long-acting biodegradable drug delivery system for
      contraceptive steroids.

PMID- 16108045
TI  - Supramolecular assemblies of adsorbed collagen affect the adhesion of endothelial
      cells.
AB  - The behavior of endothelial cells (HUVECs) in contact with thin collagen films
      presenting different supramolecular organizations was investigated. Collagen was
      adsorbed on polystyrene (PS) and plasma-oxidized PS (PSox) in conditions ensuring
      the formation of continuous layers presenting an increasing density of fibrillar
      structures. Discontinuous collagen layers were also prepared on PS by adsorption
      followed by dewetting. The morphology of the obtained collagen films was checked
      by using atomic force microscopy. HUVECs adhesion was evaluated in terms of cell
      number, cell area, cell shape, and actin structure after 4 h of contact with the
      prepared collagen layers. In the presence of serum, no adhesion was observed on
      PS, whereas a substantial adhesion was found on PSox. This is explained by the
      competition for adsorption, which turns in favor of adhesive proteins secreted by
      the cells on the hydrophilic PSox, but turns in favor of serum albumin on the
      hydrophobic PS. The progressive coating of PS by smooth collagen films increased
      cell adhesion and spreading. However, cell spreading and cytoskeleton
      organization were adversely affected by the appearance of a high density of
      collagen fibrillar structures. This latter trend was similarly observed on PSox.
      On the other hand, HUVECs spreading and cytoskeleton organization were clearly
      enhanced on discontinuous collagen layers compared with continuous ones. A
      possible explanation for these observations lies in the modification of exposure
      and/or spatial distribution of recognition sequences due to spontaneous collagen
      self-assembly on fibril formation or to collagen aggregation on dewetting.

PMID- 16108046
TI  - The third gas: H2S regulates perfusion pressure in both the isolated and perfused
      normal rat liver and in cirrhosis.
AB  - The regulation of sinusoidal resistance is dependent on the contraction of
      hepatic stellate cells (HSC) around sinusoidal endothelial cell (SEC) through
      paracrine cross-talk of vasoconstrictor and vasodilator agents. Hydrogen sulfide
      (H2S), a recently discovered gas neurotransmitter, is a putative vasodilator
      whose role in hepatic vascular regulation and portal hypertension is unexplored.
      Four-week bile duct-ligated (BDL) rats with cirrhosis and control rats were
      treated daily with NaHS (56 micromol/kg) for 5 days. Isolated livers were
      perfused first with NaHS for 20 minutes and then with norepinephrine (NE) and the
      intrahepatic resistance studied. In normal rats and animals with cirrhosis,
      administration of NE resulted in a dose-dependent increase of portal pressure.
      This effect was attenuated by H2S treatment (P < .05). The H2S-induced relaxation
      of hepatic microcirculation was attenuated by glibenclamide, an adenosine
      triphosphate (ATP)-sensitive K+ channel inhibitor. L-Cysteine, a substrate of
      cystathionine-gamma-lyase (CSE), decreased vasoconstriction in normal rat livers
      (P < .05) but failed to do so in livers with cirrhosis. BDL resulted in a
      downregulation of CSE mRNA/protein levels and activity (P < .05). Our in vitro
      data demonstrate that CSE is expressed in hepatocytes, HSCs, but not in
      sinusoidal endothelial cells (SEC). HSC activation downregulates CSE mRNA
      expression, resulting in a defective production of H2S and abrogation of
      relaxation induced by L-cysteine. In conclusion, CSE-derived H2S is involved in
      the maintenance of portal venous pressure. The reduction of CSE expression in the
      liver with cirrhosis contributes to the development of increased intrahepatic
      resistance and portal hypertension.

PMID- 16108047
TI  - Crosslinking of collagen with dendrimers.
AB  - Polypropyleneimine octaamine dendrimers were studied as an alternative means of
      generating highly crosslinked collagen. Crosslinking was effected by using the
      water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide
      hydrochloride (EDC). The multifunctional dendrimers were introduced as novel
      crosslinkers after the activation of the carboxylic acid groups of glutamic and
      aspartic acid residues in collagen. The conventional crosslinker glutaraldehyde
      was used as a control. EDC, itself an alternative crosslinker, which forms zero
      length crosslinks by directly covalently binding collagen molecules, as well as a
      low molecular weight diamine and a low molecular weight triamine, were also
      studied. All of the resultant gels were freeze-dried to obtain sponges for
      characterization. Water uptake of the gels decreased from 90% to 60% after
      dendrimer crosslinking compared with EDC crosslinking. DSC results showed an
      increase of denaturation temperature of collagen after crosslinking with the
      various methods. The generation 2 and 3 dendrimer-crosslinked collagen samples
      had the highest denaturation temperature, at up to 90 degrees C compared with 50
      degrees C in the uncrosslinked collagen control. The dendrimer-crosslinked
      collagen also showed unique thermal characteristics, with multiple denaturation
      temperature peaks in contrast to the single peak noted with the other crosslinked
      collagens. This is thought to be due to the heterogeneous nature of dendrimer
      crosslinking. Collagenase results revealed that the dendrimer-crosslinked
      collagen had a comparative resistance to proteolysis to glutaraldehyde
      crosslinked collagen. Measurement of activated carboxylic acid groups before and
      after crosslinking indicated that 40-70% of the activated carboxylic acid was
      consumed during crosslinking with dendrimers. The results suggest that dendrimer
      crosslinking of collagen produces stable gels. The presence of a large number of
      excess amine groups in the dendrimers may also be useful for subsequent
      modification with biologically relevant groups.

PMID- 16108048
TI  - Detailed considerations for a balanced and broadly applicable force field: a
      study of substituted benzenes modeled with OPLS-AA.
AB  - Modern classical force fields have been traditionally parameterized by attempting
      to maximize agreement to any number of experimental and/or quantum mechanical
      target properties. As these force fields are pushed towards obtaining
      quantitative estimates of often subtle energetic differences, stringent and
      consistent parameterization criteria, particularly in regard to charge
      distributions, are required to ensure that systematic errors cancel, that
      parameters are transferable between molecules, and that performance does not
      significantly deteriorate when using more approximate methods, such as with
      continuum solvent models. Relative free energies of hydration are presented here
      for 40 mono- and disubstituted benzenes modeled with the OPLS-AA force field;
      heats of vaporization and pure liquid densities at standard conditions are
      presented when experimental data is available. Overall agreement between OPLS-AA
      and experiment is remarkable (average error = 0.5 kcal/mol for
      DeltaDeltaG(hydration), 1.0 kcal/mol for DeltaH(vap) (0), 0.02 g/mL for
      densities), yet several functional groups are identified as having consistent and
      correctable errors (alkyl-, nitro-, and thiobenzenes). Relative free energies of
      hydration obtained with rigorous free energy perturbations using explicit solvent
      are also compared with energies from minimizations using a generalized Born model
      (GB). There is high correlation between these estimates (R = 0.99), and as
      demonstrated here, reparameterization of the aforementioned groups can be guided
      with rapid GB calculations.

PMID- 16108049
TI  - Graphical approach to analyzing DNA sequences.
AB  - Recently, we proposed a 2D graphical representation of DNA sequence [J Comput
      Chem 25(2004) 1364-1368]. Based on this representation, we outline one approach
      to search optimal alignment. We also can judge the mutations between bases and an
      unknown sequence based on its graph and a known sequence's graph.

PMID- 16108050
TI  - On the feasibility of phosphate glass and hydroxyapatite engineered coating on
      titanium.
AB  - In this report, bioactive calcium phosphate (CaP) coatings were produced on
      titanium (Ti) by using phosphate-based glass (P-glass) and hydroxyapatite (HA),
      and their feasibility for hard tissue applications was addressed in vitro. P
      glass and HA composite slurries were coated on Ti under mild heat treatment
      conditions to form a porous thick layer, and then the micropores were filled in
      with an HA sol-gel precursor to produce a dense layer. The resultant coating
      product was composed of HA and calcium phosphate glass ceramics, such as
      tricalcium phosphate (TCP) and calcium pyrophosphate (CPP). The coating layer had
      a thickness of approximately 30-40 microm and adhered to the Ti substrate
      tightly. The adhesion strength of the coating layer on Ti was as high as 30-33
      MPa. The human osteoblastic cells cultured on the coatings produced by the
      combined method attached and proliferated favorably. Moreover, the cells on the
      coatings expressed significantly higher alkaline phosphatase activity than those
      on pure Ti, suggesting the stimulation of the osteoblastic activity on the
      coatings. On the basis of these observations, the engineered CaP coating layer is
      considered to be potentially applicable as a hard tissue-coating system on Ti
      based implants.

PMID- 16108051
TI  - Role of adiponectin in the protective action of dietary saturated fat against
      alcoholic fatty liver in mice.
AB  - The protective effect of dietary saturated fatty acids against the development of
      alcoholic liver disease has long been known, but the underlying mechanism is not
      completely understood. We examined the involvement of the adipocyte hormone
      adiponectin. Circulating adiponectin levels were significantly elevated by
      chronic ethanol administration to mice consuming a diet high in saturated fat.
      The increase in circulating adiponectin was associated with the activation a set
      of hepatic signaling pathways mediated through AMP-activated protein kinase, PPAR
      alpha, and PPAR-gamma coactivator alpha, which in turn led to markedly increased
      rates of fatty acid oxidation, prevention of hepatic steatosis, and alleviation
      of liver enzyme changes. Furthermore, treatment of rat 3T3-L1 adipocytes with
      saturated fatty acids (palmitic or stearic acids) in the presence of ethanol
      increased secretion of adiponectin and enhanced activity of a mouse adiponectin
      promoter. In conclusion, the protective action of saturated fat against the
      development of alcoholic fatty liver in mice is partially mediated through
      induction of adiponectin. The present findings suggest a novel paradigm for
      dietary fatty acids in the pathogenesis of alcoholic liver disease and provide a
      promising therapeutic strategy-nutritional modulation of adiponectin-in treating
      human alcoholic fatty liver disease.

PMID- 16108052
TI  - Occupational factors and risk of adult bone sarcomas: a multicentric case-control
      study in Europe.
AB  - We investigated the association between occupational factors and risk of bone
      sarcoma, a rare tumor with a largely unknown aetiology. A multicentric case
      control study was conducted in 7 European countries in 1995-97. Ninety-six cases
      aged 35-69 years with a centrally reviewed diagnosis of bone sarcoma (68
      chondrosarcomas and 28 osteosarcomas) were compared to 2,632 population (68%) or
      colon cancer (32%) controls. Subjects were interviewed to obtain information on
      occupational, medical and reproductive history, smoking and alcohol consumption
      and selected exposures including use of pesticides. Response proportions were 90%
      among cases and 66% among controls. Odds ratios (OR) and 95% confidence intervals
      (CI) were estimated for selected categories of job titles and branches of
      industry and for use of pesticides. We found an increased OR for bone sarcoma
      among blacksmiths, toolmakers, machine-tool operators (OR = 2.14, 95% CI 1.08
      4.26), woodworkers (OR = 2.68, 95% CI 1.36-5.29) and construction workers (OR =
      1.62, 95% CI 0.92-2.87). Ever users of pesticide had an OR of 2.33 (95% CI 1.31
      4.13), with similar risks for exposure to insecticides and exposure to
      herbicides. Neither duration of employment in any of the analyzed occupational
      categories nor duration of use of pesticides showed an increasing trend in the
      risk of bone sarcoma. ORs of bone sarcoma were 1.03 (95% CI 0.23-4.57), 3.13 (95%
      CI 1.26-7.76) and 1.44 (95% CI 0.43-4.85) for the first, second and third tertile
      of days of use of pesticides. Our study suggests that novel and previously
      reported (woodworking) occupational factors play a role in the aetiology of bone
      sarcomas.

PMID- 16108053
TI  - The phase state of NiTi implant material affects osteoclastic attachment.
AB  - In the present work, the responses of mature osteoclasts cultured on austenite
      and martensite phases of NiTi shape memory implant material were studied. We used
      the sensitivity of osteoclasts to the underlying substrate and actin ring
      formation as an indicator of the adequacy of the implant surface. The results
      showed osteoclasts with actin ring on both NiTi phases. However, significantly
      more osteoclasts were present on the austenitic NiTi than on the martensitic
      NiTi. We also analyzed the surface free energy of the samples but found no
      significant difference between austenite and martensite phases. The results
      revealed that osteoclasts tolerated well the austenite phase of NiTi. The
      chemically identical martensitic NiTi was not as well tolerated by osteoclasts
      (e.g., indicated by diminished actin ring formation). This leads to the
      conclusion that certain physical properties specific to the martensitic NiTi have
      an adverse effect to the surviving of osteoclasts on this NiTi phase. These
      results confirm that mature, authentic osteoclasts can act as cell probes in
      experiments concerning aspects of biocompatibility of bone implant materials.

PMID- 16108054
TI  - Benchmarking approximate density functional theory. I. s/d excitation energies in
      3d transition metal cations.
AB  - The performance of a number of different implementations of density functional
      theory (DFT) for predicting the s/d interconfigurational energies of the 3d
      transition metal cations is investigated. Systematic comparisons of computed
      results with experimental data indicate that gradient corrected correlation
      functionals, like the LYP GGA, efficiently correct the flaws of the LDA, but
      reveal shortcomings in the treatment of exchange by currently available GGAs. The
      admixture of exact exchange in hybrid functionals eventually leads to largely
      reduced errors. Several basis sets available for the 3d elements are tested in
      combination with the B3LYP functional. Finally, the influence of variations of
      the admixture of exact exchange is systematically tested. The results reveal that
      computed s/d excitation energies obtained for the individual ions depend in
      markedly different ways on the amount of exact exchange admixture and that there
      is no single optimal and transferable exchange parameter to create a hybrid
      functional that yields improved results for all ions alike. Several of the
      recently devised functionals perform as good as or slightly better than the B3LYP
      functional in the present study. But given the fact that the B3LYP functional has
      been identified as the most successful DFT method in an overwhelming number of
      systematic investigations in very many areas of chemical research, there is no
      persuasive motivation to recommend its replacement by one of the other
      functionals, as much less is known about their robustness.

PMID- 16108055
TI  - Modeling lanthanide complexes: sparkle/AM1 parameters for ytterbium (III).
AB  - The Sparkle/AM1 model is extended to ytterbium (III) complexes. Thus, a set of 15
      complexes, with various representative ligands, chosen to be representative of
      all complexes of high crystallographic quality (R-factor <0.05 A) in the
      Cambridge Crystallographic Database, and which possess oxygen and/or nitrogen as
      coordinating atoms, was used as the training set. In the validation procedure we
      added 32 more high quality crystallographic structures. For the 47 complexes, the
      Sparkle/AM1 unsigned mean error for all interatomic distances between the Yb(III)
      ion and the ligand atoms of the first sphere of coordination is 0.07 A, similar
      to present-day ab initio/ECP geometry prediction accuracies, and potentially
      useful for luminescent complex design while being hundreds of times faster.

PMID- 16108056
TI  - Proliferation and Cdk4 expression in microsatellite unstable colon cancers with
      TGFBR2 mutations.
AB  - Approximately 15% of human colon cancers have microsatellite instability (MSI)
      and carry frameshift mutations in a polyadenine tract (BAT-RII) in the type II
      transforming growth factor beta (TGF-beta) receptor (TGFBR2), a required
      component of the TGF-beta receptor. The BAT-RII mutations in MSI colon cancers
      make the tumors resistant to the effects of TGF-beta. In cultured epithelial
      cells, TGF-beta can inhibit cell proliferation and induce apoptosis, and in vitro
      it can regulate the expression of a variety of cyclins, cyclin-dependent kinases
      (cdks) and cdk inhibitors. These effects are context- and tissue type-dependent,
      raising questions about which of these in vitro effects of TGF-beta signaling
      inactivation contribute to the formation of primary colon cancer. Thus, this
      study sought to determine the pathogenetically relevant effects of TGFBR2
      inactivation in primary MSI colon cancers with mutant BAT-RII. Colon cancers with
      mutant BAT-RII were found to have increased proliferation compared to cancers
      with wild-type BAT-RII. Assessment of cdk4, cyclin D1 and p27(kip1) expression
      revealed that only cdk4 expression was increased in the cancers with mutant BAT
      RII. In order to determine if TGFBR2 inactivation was the cause of these changes,
      TGFBR2 was reconstituted in an MSI colon cancer cell line, resulting in decreased
      proliferation and decreased cdk4 expression and kinase activity. These results
      suggest that TGFBR2 mutations in primary colon cancers may be responsible for the
      increased proliferation and cdk4 expression in these tumors and provide evidence
      that deregulation of cdk4 is a pathogenic in vivo consequence of TGFBR2
      inactivation in primary colon cancer.

PMID- 16108057
TI  - Distinct regulation and impact of type 1 T-cell immunity against HPV16 L1, E2 and
      E6 antigens during HPV16-induced cervical infection and neoplasia.
AB  - Cervical cancer is the possible outcome of a genital infection with high-risk
      human papillomavirus type 16 (HPV16) and is preceded by a phase of persistent HPV
      infection during which the host immune system fails to eliminate the virus. Our
      previous work showed that failure is reflected by the absence of type 1 T-cell
      immunity against HPV16 early antigens E2 and E6 in patients with HPV16+ cervical
      lesions. We now show that a majority of both patients with cervical lesions and
      healthy subjects display HPV16 L1 peptide-specific type 1 T-cell responses with
      similar magnitude. The T-cell response in patients was directed at a broad range
      of peptides within L1, suggesting that during persistent or repeated exposure to
      HPV16 L1, the immune system maximizes its efforts to counter the viral challenge.
      Unlike the type 1 T-cell responses against HPV16 early antigens E2 and E6, type 1
      T-cell immunity against L1 does not correlate with health or disease. This argues
      that T-cell responses against early and late HPV16 antigens essentially differ in
      the manner in which they are induced and regulated, as well as in their impact on
      the subsequent stages of HPV16-induced cervical disease.

PMID- 16108058
TI  - Novel approach for quantification of porosity for biomaterial implants using
      microcomputed tomography (microCT).
AB  - Porous bioceramics have been widely investigated in orthopaedic tissue
      engineering. Attention has been given to manufacturing of a porous bioceramic
      that mimics the trabecular bone structure for proper bone regeneration. With the
      advance of biomedical imaging through microcomputed tomography (microCT), this
      study attempted to quantify the pore structure of different bioceramics. Two
      bioceramic blocks (BSC and ChronOS) were synthesized by two methods. The
      specification claimed the porosity of the bioceramic ranged from 40% to 70%. Six
      blocks of each bioceramic were evaluated by conventional water immersion method
      and microCT. The pore size and connectivity were evaluated with standardized
      protocols. By the water immersion method, the porosity of BSC and ChronOS was
      60.4% and 74.7%, respectively. The three-dimensional results of microCT showed
      that BSC porosity was 26.2% and ChronOS was 60.0%. The pore connectivity was
      evaluated to be 2.6 for BSC and 39.7 for ChronOS. ChronOS had functional pores
      with 200 microm to 400 microm in diameter (87.8%+/-0.5%), which is significantly
      more than 52.8%+/-11.5% of pores in BSC (p<0.05). Providing information on the
      functional pores objectively, the microCT evaluation serves as a good standard
      for specification of the bioceramic-related implants.

PMID- 16108059
TI  - Analysis of ISG expression in chronic hepatitis C identifies viperin as a
      potential antiviral effector.
AB  - Interferon (IFN) alpha inhibits hepatitis C virus (HCV) replication both
      clinically and in vitro; however, the complete spectrum of interferon-stimulated
      genes (ISGs) expressed in the HCV-infected liver or the genes responsible for
      control of HCV replication have not been defined. To better define ISG expression
      in the chronically infected HCV liver, DNA microarray analysis was performed on 9
      individuals with chronic hepatitis C (CHC). A total of 232 messenger RNAs were
      differentially regulated in CHC compared with nondiseased liver controls. A
      significant proportion of these were potential ISGs that were transcriptionally
      elevated, suggesting an ongoing response to endogenous IFN and/or double-stranded
      RNA. One ISG significantly elevated in all patients was viperin, an evolutionary
      conserved ISG that has antiviral activity against human cytomegalovirus.
      Stimulation of Huh-7 and HepG2 cells with IFN-alpha or -gamma revealed viperin is
      predominantly a type I ISG. Furthermore, viperin expression could also be induced
      following transfection of Huh-7 cells with either poly(I:C) or HCV RNA. Transient
      expression of viperin in cells harboring the HCV genomic replicon resulted in a
      significant decrease in HCV replication, suggesting that viperin has anti-HCV
      activity. In conclusion, even in the face of a persistent HCV infection, there is
      an active ISG antiviral cellular response, highlighting the complexity of the
      host viral relationship. Furthermore, ISG viperin has anti-HCV activity in vitro;
      we postulate that viperin, along with other ISGs, acts to limit HCV replication.

PMID- 16108060
TI  - Paralogs and mutational robustness linked through transcriptional reprogramming.
AB  - A recent analysis of genome-wide expression patterns and regulatory motif content
      of paralogous yeast genes strongly suggests that mutational robustness (backup)
      between paralogous genes is achieved via transcriptional reprogramming of one
      paralog to compensate for the loss or silencing of the other.

PMID- 16108061
TI  - Peptides of love and fear: vasopressin and oxytocin modulate the integration of
      information in the amygdala.
AB  - Neuropeptides vasopressin and oxytocin regulate a variety of behaviors ranging
      from maternal and pair bonding to aggression and fear. Their role in modulating
      fear responses has been widely recognized, but not yet well understood. Animal
      and human studies indicate the major role of the amygdala in controlling fear and
      anxiety. The amygdala is involved in detecting threat stimuli and linking them to
      defensive behaviors. This is accomplished by projections connecting the central
      nucleus of the amygdala (CeA) to the brain stem and to hypothalamic structures,
      which organize fear responses. A recent study by Huber et al demonstrates that
      vasopressin and oxytocin modulate the excitatory inputs into the CeA in opposite
      manners. Therefore this finding elucidates the mechanisms through which these
      neuropeptides may control the expression of fear.

PMID- 16108062
TI  - Evolution of early development of the nervous system: a comparison between
      arthropods.
AB  - Large numbers of cells with unique neuronal specificity are generated during
      development of the central nervous system of animals. Here we discuss the events
      that generate cell diversity during early development of the ventral nerve cord
      of different arthropod groups. Neural precursors are generated in a spatial array
      in the epithelium of each hemisegment over a period of time. Spatial cues within
      the epithelium are thought to evolve as embryogenesis proceeds. This
      spatiotemporal information might generate diversity among the neural precursors
      in all arthropod groups, although the mechanisms regulating the positioning of
      individual precursors have diverged. However, distinct strategies for the
      generation of neuronal diversity have evolved in the different arthropod lineages
      that appear to correlate with specific modes of ontogenesis. We hypothesize that
      an evolutionary trend towards reduced cell numbers and possibly rapid
      embryogenesis in insects has culminated in the appearance of stereotyped
      neuroblast lineages.

PMID- 16108063
TI  - Regulation of BRCA1, BRCA2 and BARD1 intracellular trafficking.
AB  - The subcellular location and function of many proteins are regulated by nuclear
      cytoplasmic shuttling. BRCA1 and BARD1 provide an interesting model system for
      understanding the influence of protein dimerization on nuclear transport and
      localization. These proteins function predominantly in the nucleus to regulate
      cell cycle progression, DNA repair/recombination and gene transcription, and
      their export to the cytoplasm has been linked to apoptosis. Germ-line mutations
      in the BRCA1/BRCA2 and BARD1 genes predispose to risk of breast/ovarian cancer,
      and certain mutations impair protein function and nuclear accumulation. BRCA1 and
      BARD1 shuttle between the nucleus and cytoplasm; however heterodimerization masks
      the nuclear export signals located within each protein, causing nuclear retention
      of the BRCA1-BARD1 complex and potentially influencing its role in DNA repair,
      cell survival and regulation of centrosome duplication. This review discusses
      BRCA1, BRCA2 and BARD1 subcellular localization with emphasis on regulation of
      transport by protein dimerization and its functional implications.

PMID- 16108064
TI  - ECM degrading proteases and tissue remodelling in the mammary gland.
AB  - Matrix degradation and tissue remodelling directed by matrix-degrading proteases
      are activated in physiological situations such as wound healing and involution of
      the prostate, ovaries and uterus. Recently, other activities, in addition to the
      cleavage of matrix proteins, have been attributed to matrix proteases including
      the release of growth factors from the extracellular matrix and roles in the
      maturation of adipocytes. This review describes extracellular proteases,
      including MMPs, plasminogen and cathepsins involved in the tissue remodelling
      processes that occur in the breast during pubertal mammary development and the
      mammary cycle of pregnancy, lactation and weaning. It particularly focuses on
      development and weaning, termed mammary gland involution, when the majority of
      remodelling occurs. It also brings together recent findings on the exciting new
      functions of matrix-degrading proteases.

PMID- 16108065
TI  - How to get ahead: the origin, evolution and function of bicoid.
AB  - In Drosophila, a Bcd protein gradient orchestrates patterning along the
      anteroposterior embryonic axis. However, studies of basal flies and other insects
      have revealed that bcd is a derived Hox3 gene found only in higher dipterans. To
      understand how bcd acquired its role in flies and how anteroposterior patterning
      mechanisms have evolved, I first review key features of bcd function in
      Drosophila: anterior localization and transcriptional and translation control of
      gene expression. I then discuss investigations of bcd in other higher dipterans
      that have provided insight into the evolution of regulatory interactions and the
      Bcd gradient. Finally, I review studies of Drosophila and other insects that
      address the evolution of bcd function and integration of bcd into ancestral
      regulatory mechanisms. I suggest further comparative studies may allow us to
      identify the intermediate steps in bcd evolution. This will make bcd a paradigm
      for the origin and evolution of genes and regulatory networks.

PMID- 16108066
TI  - The structure of photosystem I and evolution of photosynthesis.
AB  - Oxygenic photosynthesis is the principal producer of both oxygen and organic
      matter on earth. The primary step in this process--the conversion of sunlight
      into chemical energy--is driven by four multi-subunit membrane protein complexes
      named photosystem I, photosystem II, cytochrome b(6)f complex and F-ATPase.
      Photosystem I generates the most negative redox potential in nature and thus
      largely determines the global amount of enthalpy in living systems. The recent
      structural determination of PSI complexes from cyanobacteria and plants sheds
      light on the evolutionary forces that shaped oxygenic photosynthesis. The
      fortuitous formation of our solar system in a space plentiful of elements, our
      distance from the sun and the long time of uninterrupted evolution enabled the
      perfection of photosynthesis and the evolution of advanced organisms. The
      available structural information complements the knowledge gained from genomic
      and proteomic data to illustrate a more precise scenario for the evolution of
      life systems on earth.

PMID- 16108067
TI  - Evolution of the neural basis of consciousness: a bird-mammal comparison.
AB  - The main objective of this essay is to validate some of the principal, currently
      competing, mammalian consciousness-brain theories by comparing these theories
      with data on both cognitive abilities and brain organization in birds. Our
      argument is that, given that multiple complex cognitive functions are correlated
      with presumed consciousness in mammals, this correlation holds for birds as well.
      Thus, the neuroanatomical features of the forebrain common to both birds and
      mammals may be those that are crucial to the generation of both complex cognition
      and consciousness. The general conclusion is that most of the consciousness-brain
      theories appear to be valid for the avian brain. Even though some specific
      homologies are unresolved, most of the critical structures presumed necessary for
      consciousness in mammalian brains have clear homologues in avian brains.
      Furthermore, considering the fact that the reptile-bird brain transition shows
      more structural continuity than the stem amniote-mammalian transition, the line
      drawn at the origin of mammals for consciousness by several of the theorists
      seems questionable. An equally important point is that consciousness cannot be
      ruled out in the absence of complex cognition; it may in fact be the case that
      consciousness is a necessary prerequisite for complex cognition.

PMID- 16108068
TI  - From 2R to 3R: evidence for a fish-specific genome duplication (FSGD).
AB  - An important mechanism for the evolution of phenotypic complexity, diversity and
      innovation, and the origin of novel gene functions is the duplication of genes
      and entire genomes. Recent phylogenomic studies suggest that, during the
      evolution of vertebrates, the entire genome was duplicated in two rounds (2R) of
      duplication. Later, approximately 350 mya, in the stem lineage of ray-finned
      (actinopterygian) fishes, but not in that of the land vertebrates, a third genome
      duplication occurred-the fish-specific genome duplication (FSGD or 3R), leading,
      at least initially, to up to eight copies of the ancestral deuterostome genome.
      Therefore, the sarcopterygian (lobe-finned fishes and tetrapods) genome possessed
      originally only half as many genes compared to the derived fishes, just like the
      most-basal and species-poor lineages of extant fishes that diverged from the fish
      stem lineage before the 3R duplication. Most duplicated genes were secondarily
      lost, yet some evolved new functions. The genomic complexity of the teleosts
      might be the reason for their evolutionary success and astounding biological
      diversity.

PMID- 16108069
TI  - Significance and therapeutic potential of prostaglandin E2 receptor in hepatic
      ischemia/reperfusion injury in mice.
AB  - Prostaglandin E2 (PGE2) mediates a variety of innate and adaptive immunity
      through four distinct receptors: EP1-EP4. It has been suggested that each EP
      plays a unique and pivotal role in various disease conditions. We investigated
      the pathophysiological role of EP receptors in hepatic ischemia/reperfusion (I/R)
      injury. In this study, a 70% hepatic ischemic model was used in male C57BL/6
      mice. Selective EP agonists were used to clarify the function of each PGE2
      receptor in I/R injury. Although all four receptors were expressed in the naive
      liver, EP4 expression was significantly upregulated after hepatic I/R. Although
      EP1, 2, or 3 agonists did not show any protective effect on liver function, the
      EP4 agonist significantly inhibited hepatic I/R injury as determined by
      serological and histological analyses. Furthermore, the EP4 agonist downregulated
      the local expressions of several proinflammatory cytokines, chemokines, and
      adhesion molecules in the early phase of reperfusion. In contrast, it augmented
      the local expression of an anti-inflammatory cytokine, interleukin 10.
      Additionally, the neutrophil accumulation was also inhibited by EP4 agonist
      treatment. Finally, to confirm the therapeutic efficacy of the EP4 agonist in
      hepatic I/R injury, the nonischemic shunt liver was removed after 120 minutes of
      ischemia, resulting in the death of 86% of control mice within 48 hours. In sharp
      contrast, 80% of mice treated with the EP4 agonist survived. In conclusion, the
      PGE2-EP4 signaling pathway has an inhibitory role in hepatic I/R injury. An EP4
      agonist effectively protects against ischemic injury.

PMID- 16108070
TI  - Lung cancer risks in relation to vegetable and fruit consumption and smoking.
AB  - In a case-control study on lung cancer, risk was analysed in relation to smoking
      habits and frequency of vegetable and fruit consumption. Lung cancer cases in
      West Sweden and population controls were interviewed using a questionnaire where
      the frequency of consumption of dietary items and smoking habits were assessed.
      The material presented comprises 177 female and 359 male confirmed cases of lung
      cancer and 916 population controls. There was a dose-response relationship in
      regard to the number of cigarettes smoked and the number of years smoked, the
      latter factor being more important. After adjustment for number of cigarettes
      smoked/day and number of years smoked, the risk for those who seldom consumed
      vegetables was about twice of that among those who consumed vegetables
      frequently, both among nonsmokers, smokers and former smokers. This risk increase
      in relation to vegetable consumption also was present for different smoking
      categories. A similar tendency, although less pronounced, was found for fruit
      consumption. The results demonstrate that dietary factors are related to the risk
      for lung cancer, although smoking is the dominant risk factor.

PMID- 16108071
TI  - Iron accelerates the conversion of dopamine-oxidized intermediates into melanin
      and provides protection in SH-SY5Y cells.
AB  - Parkinson's disease (PD) is characterized by the selective loss of dopaminergic
      neurons in the substantia nigra (SN), and it has been suggested that dopamine is
      one of the main endogenous toxins in the genesis of PD. We demonstrated that
      thiol antioxidants (the reduced form of glutathione, N-acetyl-L-cysteine, and L
      cysteine), which conjugate with one dopamine oxidation intermediate, o-quinone,
      provided almost complete protection from dopamine-mediated toxicity in SH-SY5Y, a
      human neuroblastoma cell line. In contrast, catalase partially provided
      protection against cell death caused by dopamine. These data suggest that the
      generation of dopamine oxidation intermediates, rather than hydrogen peroxide,
      plays a pivotal role in dopamine-induced toxicity. Iron accumulated in the SN of
      patients with PD can cause dopaminergic neuronal degeneration by enhancing
      oxidative stress. However, we found that iron reduced the total amounts of
      dopamine oxidation intermediates and enhanced the formation of melanin, a final
      product of dopamine oxidation. Also, addition of iron inhibited dopamine-induced
      cytotoxicity. These results suggest that iron can provide protection when it
      accelerates the conversion of dopamine oxidation intermediates.

PMID- 16108072
TI  - Motoneuron degeneration after facial nerve avulsion is exacerbated in
      presymptomatic transgenic rats expressing human mutant Cu/Zn superoxide
      dismutase.
AB  - We investigated motoneuron degeneration after proximal nerve injury in
      presymptomatic transgenic (tg) rats expressing human mutant Cu/Zn superoxide
      dismutase (SOD1). The right facial nerves of presymptomatic tg rats expressing
      human H46R or G93A SOD1 and their non-tg littermates were avulsed, and facial
      nuclei were examined at 2 weeks postoperation. Nissl-stained cell counts revealed
      that facial motoneuron loss after avulsion was exacerbated in H46R- and G93A-tg
      rats compared with their non-tg littermates. The loss of motoneurons in G93A-tg
      rats after avulsion was significantly greater than that in H46R-tg rats. Intense
      cytoplasmic immunolabeling for SOD1 in injured motoneurons after avulsion was
      demonstrated in H46R- and G93A-tg rats but not in their littermates. Facial
      axotomy did not induce significant motoneuron loss nor enhance SOD1
      immunoreactivity in these tg rats and non-tg littermates at 2 weeks
      postoperation, although both axotomy and avulsion elicited intense immunolabeling
      for activating transcription factor-3, phosphorylated c-Jun, and phosphorylated
      heat shock protein 27 in injured motoneurons of all these animals. The present
      data indicate the increased vulnerability of injured motoneurons after avulsion
      in the presymptomatic mutant SOD1-tg rats.

PMID- 16108073
TI  - Quality of life in refractory ascites: transjugular intrahepatic portal-systemic
      shunting versus medical therapy.
AB  - Uncontrolled studies suggest that transjugular intrahepatic portal-systemic
      shunting (TIPS) may improve quality of life in patients with refractory ascites.
      We hypothesized that any improvement of quality of life in patients with TIPS
      would be matched in controls due to the competing effects of improved ascites and
      worsened hepatic encephalopathy. Thus, an analysis of quality of life was
      performed using original data from the North American Study for the Treatment of
      Refractory Ascites, a multicenter trial of 109 patients randomized to TIPS or
      repeated large volume paracentesis (LVP) for refractory ascites. Short form 36
      (SF-36) surveys were completed at baseline and at 6- and 12-month follow-up.
      Variables analyzed were: randomization group, number of LVP performed, cumulative
      volume from LVP, shortness of breath, abdominal distention, abdominal pain,
      diuretic usage, confusion, hospitalizations, and emergency room visits. Outcomes
      were changes in physical component scale (PCS) and mental component scale (MCS)
      of SF-36 results. We constructed multivariable, mixed effects models, including
      randomization group and baseline MCS and PCS. Changes in PCS and MCS from
      baseline were similar between the two randomization groups. In multivariate
      analysis, PCS improvement was associated with lack of confusion, improved
      ascites, and lack of hospitalizations, but not directly with randomization group.
      Improvement in MCS was associated with randomization to TIPS and lack of
      confusion. In conclusion, patients with refractory ascites randomized to TIPS or
      repeated LVP had similar changes in quality of life. Competing effects of hepatic
      encephalopathy, requirement for repeated LVP, and need for hospitalizations
      explain similar changes in quality of life between the two groups.

PMID- 16108074
TI  - Is spinal muscular atrophy the result of defects in motor neuron processes?
AB  - The hereditary neurodegenerative disease spinal muscular atrophy (SMA) with
      childhood onset is one of the most common genetic causes of infant mortality. The
      disease is characterized by selective loss of spinal cord motor neurons leading
      to muscle atrophy and is the result of mutations in the survival motor neuron
      (SMN) gene. The SMN protein has been implicated in diverse nuclear processes
      including splicing, ribosome formation and gene transcription. Even though the
      genetic basis of SMA is well understood, it is not clear how defects in these
      ubiquitous processes result in motor neuron degeneration leaving other tissues
      unaffected. Recent evidence from animal and cell culture models of SMA points to
      roles for SMN in neurite outgrowth and axonal transport. Disruption of these
      functions might be particularly detrimental to motor neurons given their high
      metabolic demands and precise connectivity requirements, thus providing a
      possible explanation for the specificity of motor neuron susceptibility in SMA.
      Understanding the molecular mechanisms of SMN activity in neuronal processes may
      generate new targets for future therapeutic strategies.

PMID- 16108075
TI  - Darwin in the genome.

PMID- 16108076
TI  - Protein-interaction mapping in search of effective drug targets.
AB  - Signaling complexes and networks are being intensely studied in an attempt to
      discover pathways that are amenable to therapeutic intervention. A challenge in
      this search is to understand the effect that the modulation of a target will have
      on the overall function of a cell and its surrounding neighbors. Protein
      interaction mapping reveals relationships between proteins and their impact on
      cellular processes and is being used more widely in our understanding of disease
      mechanisms and their treatment. The review discusses challenges and breakthroughs
      in this new and evolving area and its impact on medicine.

PMID- 16108077
TI  - Boris Balinsky: transition from embryology to developmental biology.
AB  - This is the story of a textbook that students of developmental biology have used
      for 45 years. "An Introduction to Embryology" was released soon after a role for
      genes in the control of development became finally recognized but not yet well
      documented. Thus this book manifested the transition from embryology to
      developmental biology. The story of its author, Boris Balinsky, who against all
      odds survived to write this book, is remarkable on its own. He started his
      scientific career in the USSR, but due to 20th century social and political
      upheavals, ended it in South Africa. This article will shed light on the life of
      Boris Balinsky, a scientist and writer and will explore the origins of his book.

PMID- 16108078
TI  - Aging in Esherichia coli: signals in the noise.

PMID- 16108079
TI  - Mechanism of the initial conformational transition of a photomodulable peptide.

PMID- 16108080
TI  - Hydrogen sponge? A heteronuclear cluster that absorbs large quantities of
      hydrogen.

PMID- 16108081
TI  - Towards a fully synthetic carbohydrate-based anticancer vaccine: synthesis and
      immunological evaluation of a lipidated glycopeptide containing the tumor
      associated tn antigen.

PMID- 16108082
TI  - Efficient total syntheses of (-)-colombiasin A and (-)-elisapterosin B:
      application of the Cr-catalyzed asymmetric quinone Diels-Alder reaction.

PMID- 16108083
TI  - Profile-based string kernels for remote homology detection and motif extraction.
AB  - We introduce novel profile-based string kernels for use with support vector
      machines (SVMs) for the problems of protein classification and remote homology
      detection. These kernels use probabilistic profiles, such as those produced by
      the PSI-BLAST algorithm, to define position-dependent mutation neighborhoods
      along protein sequences for inexact matching of k-length subsequences ("k-mers")
      in the data. By use of an efficient data structure, the kernels are fast to
      compute once the profiles have been obtained. For example, the time needed to run
      PSI-BLAST in order to build the profiles is significantly longer than both the
      kernel computation time and the SVM training time. We present remote homology
      detection experiments based on the SCOP database where we show that profile-based
      string kernels used with SVM classifiers strongly outperform all recently
      presented supervised SVM methods. We further examine how to incorporate predicted
      secondary structure information into the profile kernel to obtain a small but
      significant performance improvement. We also show how we can use the learned SVM
      classifier to extract "discriminative sequence motifs"--short regions of the
      original profile that contribute almost all the weight of the SVM classification
      score--and show that these discriminative motifs correspond to meaningful
      structural features in the protein data. The use of PSI-BLAST profiles can be
      seen as a semi-supervised learning technique, since PSI-BLAST leverages unlabeled
      data from a large sequence database to build more informative profiles. Recently
      presented "cluster kernels" give general semi-supervised methods for improving
      SVM protein classification performance. We show that our profile kernel results
      also outperform cluster kernels while providing much better scalability to large
      datasets.

PMID- 16108084
TI  - PoPS: a computational tool for modeling and predicting protease specificity.
AB  - Proteases play a fundamental role in the control of intra- and extra-cellular
      processes by binding and cleaving specific amino acid sequences. Identifying
      these targets is extremely challenging. Current computational attempts to predict
      cleavage sites are limited, representing these amino acid sequences as patterns
      or frequency matrices. Here we present PoPS, a publicly accessible bioinformatics
      tool (http://pops.csse.monash.edu.au/) that provides a novel method for building
      computational models of protease specificity, which while still being based on
      these amino acid sequences, can be built from any experimental data or expert
      knowledge available to the user. PoPS specificity models can be used to predict
      and rank likely cleavages within a single substrate, and within entire proteomes.
      Other factors, such as the secondary or tertiary structure of the substrate, can
      be used to screen unlikely sites. Furthermore, the tool also provides facilities
      to infer, compare and test models, and to store them in a publicly accessible
      database.

PMID- 16108085
TI  - Shannon information in complete genomes.
AB  - Shannon information in the genomes of all completely sequenced prokaryotes and
      eukaryotes are measured in word lengths of two to ten letters. It is found that
      in a scale-dependent way, the Shannon information in complete genomes are much
      greater than that in matching random sequences--thousands of times greater in the
      case of short words. Furthermore, with the exception of the 14 chromosomes of
      Plasmodium falciparum, the Shannon information in all available complete genomes
      belong to a universality class given by an extremely simple formula. The data are
      consistent with a model for genome growth composed of two main ingredients:
      random segmental duplications that increase the Shannon information in a scale
      independent way, and random point mutations that preferentially reduces the
      larger-scale Shannon information. The inference drawn from the present study is
      that the large-scale and coarse-grained growth of genomes was selectively neutral
      and this suggests an independent corroboration of Kimura's neutral theory of
      evolution.

PMID- 16108086
TI  - Multiple RNA structure alignment.
AB  - Ribonucleic Acid (RNA) structures can be viewed as a special kind of strings
      where characters in a string can bond with each other. The question of aligning
      two RNA structures has been studied for a while, and there are several successful
      algorithms that are based upon different models. In this paper, by adopting the
      model introduced in Wang and Zhang,(19) we propose two algorithms to attack the
      question of aligning multiple RNA structures. Our methods are to reduce the
      multiple RNA structure alignment problem to the problem of aligning two RNA
      structure alignments. Meanwhile, we will show that the framework of sequence
      center star alignment algorithm can be applied to the problem of multiple RNA
      structure alignment, and if the triangle inequality is met in the scoring matrix,
      the approximation ratio of the algorithm remains to be 2-2(over)n, where n is the
      total number of structures.

PMID- 16108087
TI  - A theoretical analysis of the selection of differentially expressed genes.
AB  - A great deal of recent research has focused on the challenging task of selecting
      differentially expressed genes from microarray data ("gene selection"). Numerous
      gene selection algorithms have been proposed in the literature, but it is often
      unclear exactly how these algorithms respond to conditions like small sample
      sizes or differing variances. Choosing an appropriate algorithm can therefore be
      difficult in many cases. In this paper we propose a theoretical analysis of gene
      selection, in which the probability of successfully selecting differentially
      expressed genes, using a given ranking function, is explicitly calculated in
      terms of population parameters. The theory developed is applicable to any ranking
      function which has a known sampling distribution, or one which can be
      approximated analytically. In contrast to methods based on simulation, the
      approach presented here is computationally efficient and can be used to examine
      the behavior of gene selection algorithms under a wide variety of conditions,
      even when the number of genes involved runs into the tens of thousands. The
      utility of our approach is illustrated by comparing three widely-used gene
      selection methods.

PMID- 16108088
TI  - Determining relevant features to recognize electron density patterns in x-ray
      protein crystallography.
AB  - High-throughput computational methods in X-ray protein crystallography are
      indispensable to meet the goals of structural genomics. In particular, automated
      interpretation of electron density maps, especially those at mediocre resolution,
      can significantly speed up the protein structure determination process.
      TEXTAL(TM) is a software application that uses pattern recognition, case-based
      reasoning and nearest neighbor learning to produce reasonably refined molecular
      models, even with average quality data. In this work, we discuss a key issue to
      enable fast and accurate interpretation of typically noisy electron density data:
      what features should be used to characterize the density patterns, and how
      relevant are they? We discuss the challenges of constructing features in this
      domain, and describe SLIDER, an algorithm to determine the weights of these
      features. SLIDER searches a space of weights using ranking of matching patterns
      (relative to mismatching ones) as its evaluation function. Exhaustive search
      being intractable, SLIDER adopts a greedy approach that judiciously restricts the
      search space only to weight values that cause the ranking of good matches to
      change. We show that SLIDER contributes significantly in finding the similarity
      between density patterns, and discuss the sensitivity of feature relevance to the
      underlying similarity metric.

PMID- 16108089
TI  - Recurrence time statistics: versatile tools for genomic DNA sequence analysis.
AB  - With the completion of the human and a few model organisms' genomes, and with the
      genomes of many other organisms waiting to be sequenced, it has become
      increasingly important to develop faster computational tools which are capable of
      easily identifying the structures and extracting features from DNA sequences. One
      of the more important structures in a DNA sequence is repeat-related. Often they
      have to be masked before protein coding regions along a DNA sequence are to be
      identified or redundant expressed sequence tags (ESTs) are to be sequenced. Here
      we report a novel recurrence time-based method for sequence analysis. The method
      can conveniently study all kinds of periodicity and exhaustively find all repeat
      related features from a genomic DNA sequence. An efficient codon index is also
      derived from the recurrence time statistics, which has the salient features of
      being largely species-independent and working well on very short sequences.
      Efficient codon indices are key elements of successful gene finding algorithms,
      and are particularly useful for determining whether a suspected EST belongs to a
      coding or non-coding region. We illustrate the power of the method by studying
      the genomes of E. coli, the yeast S. cervisivae, the nematode worm C. elegans,
      and the human, Homo sapiens. Our method requires approximately 6 . N byte memory
      and a computational time of N log N to extract all the repeat-related and
      periodic or quasi-periodic features from a sequence of length N without any prior
      knowledge on the consensus sequence of those features, hence enables us to carry
      out sequence analysis on the whole genomic scale by a PC.

PMID- 16108090
TI  - SPIDER: software for protein identification from sequence tags with de novo
      sequencing error.
AB  - For the identification of novel proteins using MS/MS, de novo sequencing software
      computes one or several possible amino acid sequences (called sequence tags) for
      each MS/MS spectrum. Those tags are then used to match, accounting amino acid
      mutations, the sequences in a protein database. If the de novo sequencing gives
      correct tags, the homologs of the proteins can be identified by this approach and
      software such as MS-BLAST is available for the matching. However, de novo
      sequencing very often gives only partially correct tags. The most common error is
      that a segment of amino acids is replaced by another segment with approximately
      the same masses. We developed a new efficient algorithm to match sequence tags
      with errors to database sequences for the purpose of protein and peptide
      identification. A software package, SPIDER, was developed and made available on
      Internet for free public use. This paper describes the algorithms and features of
      the SPIDER software.

PMID- 16108091
TI  - Decision tree based information integration for automated protein classification.
AB  - We propose a novel technique for automatically generating the SCOP classification
      of a protein structure with high accuracy. We achieve accurate classification by
      combining the decisions of multiple methods using the consensus of a committee
      (or an ensemble) classifier. Our technique, based on decision trees, is rooted in
      machine learning which shows that by judicially employing component classifiers,
      an ensemble classifier can be constructed to outperform its components. We use
      two sequence- and three structure-comparison tools as component classifiers.
      Given a protein structure and using the joint hypothesis, we first determine if
      the protein belongs to an existing category (family, superfamily, fold) in the
      SCOP hierarchy. For the proteins that are predicted as members of the existing
      categories, we compute their family-, superfamily-, and fold-level
      classifications using the consensus classifier. We show that we can significantly
      improve the classification accuracy compared to the individual component
      classifiers. In particular, we achieve error rates that are 3-12 times less than
      the individual classifiers' error rates at the family level, 1.5-4.5 times less
      at the superfamily level, and 1.1-2.4 times less at the fold level.

PMID- 16108092
TI  - Suregene, a scalable system for automated term disambiguation of gene and protein
      names.
AB  - Researchers, hindered by a lack of standard gene and protein-naming conventions,
      endure long, sometimes fruitless, literature searches. A system that is able to
      automatically assign gene names to their LocusLink ID (LLID) in previously unseen
      MEDLINE abstracts is described. The system is based on supervised learning and
      builds a model for each LLID. The training sets for all LLIDs are extracted
      automatically from MEDLINE references in the LocusLink and SwissProt databases. A
      validation was done of the performance for all 20,546 human genes with LLIDs. Of
      these, 7344 produced good quality models (F-measure >0.7, nearly 60% of which
      were >0.9) and 13,202 did not, mainly due to insufficient numbers of known
      document references. A hand validation of MEDLINE documents for a set of 66 genes
      agreed well with the system's internal accuracy assessment. It is concluded that
      it is possible to achieve high quality gene disambiguation using scaleable
      automated techniques.

PMID- 16108093
TI  - Identification of cell surface marker candidates on SV-T2 cells using DNA
      microarray on DLC-coated glass.
AB  - We analyzed gene expression profiles of normal mouse fibroblast BALB/c 3T3 cells
      and its SV40 transformant SV-T2 cells using our originally developed cell surface
      marker DNA microarray, which is prepared on a diamond-like carbon-coated glass.
      As a result, CD62L and IL-6 receptor alpha gene expressions were upregulated in
      SV-T2 and were thought to be candidates for call surface markers of the cells.
      The result of microarray analysis was validated by real-time quantitative PCR
      immunohistochemistry and biological assays. These data show that our cell surface
      marker DNA microarray should be useful in finding the candidates of cell type
      specific surface markers.

PMID- 16108094
TI  - Withanolides, a new class of natural cholinesterase inhibitors with calcium
      antagonistic properties.
AB  - The withanolides 1-3 and 4-5 isolated from Ajuga bracteosa and Withania
      somnifera, respectively, inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and
      butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent
      fashion with IC50 values ranging between 20.5 and 49,2 microm and 29.0 and 85.2
      microm for AChE and BChE, respectively. Lineweaver-Burk as well as Dixon plots
      and their secondary replots indicated that compounds 1, 3, and 5 are the linear
      mixed-type inhibitors of AChE, while 2 and 4 are non-competitive inhibitors of
      AChE with K(i) values ranging between 20.0 and 45.0 microm. All compounds were
      found to be non-competitive inhibitors of BChE with K(i) values ranging between
      27.7 and 90.6 microm. Molecular docking study revealed that all the ligands are
      completely buried inside the aromatic gorge of AChE, while compounds 1, 3, and 5
      extend up to the catalytic triad. A comparison of the docking results showed that
      all ligands generally adopt the same binding mode and lie parallel to the surface
      of the gorge. The superposition of the docked structures demonstrated that the
      non-flexible skeleton of the ligands always penetrates the aromatic gorge through
      the six-membered ring A, allowing their simultaneous interaction with more than
      one subsite of the active center. The affinity of ligands with AChE was found to
      be the cumulative effects of number of hydrophobic contacts and hydrogen bonding.
      Furthermore, all compounds also displayed dose-dependent (0.005-1.0 mg/mL)
      spasmolytic and Ca2+ antagonistic potentials in isolated rabbit jejunum
      preparations, compound 4 being the most active with an ED50 value of 0.09 +/-
      0.001 mg/mL and 0.22 +/- 0.01 microg/mL on spontaneous and K+ -induced
      contractions, respectively. The cholinesterase inhibitory potential along with
      calcium antagonistic ability and safe profile in human neutrophil viability assay
      could make compounds 1-5 possible drug candidates for further study to treat
      Alzheimer's disease and associated problems.

PMID- 16108095
TI  - A cross-sectional study of human craniofacial growth.
AB  - It is generally accepted that different cranial regions do not follow the same
      growth pattern. In this study, size changes of the functional cranial components
      (FCCs) in 228 human skulls of age at death between 0 and 20 years were evaluated.
      The skull is considered as divided into anteroneural, midneural, posteroneural,
      otic, optic, respiratory, masticatory and alveolar FCCs. Age-related changes of
      FCCs were assessed by fitting curves with the smoothing spline method, and
      quantifying the proportional increments at different stages. All FCCs show a high
      growth rate in the first 3-5 years of life. Two groups of growth trajectories can
      be distinguished. The anteroneural, midneural, posteroneural and optic FCCs are
      more advanced at all stages; they show a high growth rate before 3-5-years-old
      and a low rate later. This difference is less pronounced in the group comprising
      the respiratory, masticatory and otic FCCs. The alveolar FCC shows an independent
      pattern. The similarities among FCCs of the two groups are best explained by
      their common embryological origin. In contrast, the participation in a common
      function cannot be associated with the co-ordinated variation, given that the
      masticatory and alveolar FCCs show independent trajectories.

PMID- 16108096
TI  - The use of DREEM as curriculum need analysis tool.

PMID- 16108097
TI  - Bibliography. Current world literature. Renal pathophysiology.

PMID- 16108098
TI  - Bibliography. Current world literature. Nutrition in wasting disease.

PMID- 16108099
TI  - Bibliography. Current world literature. Carbohydrates.

PMID- 16108100
TI  - A histochemical and immunohistochemical analysis of the subependymal layer in the
      normal and Huntington's disease brain.
AB  - Previous studies in the rodent brain have characterised the cell types present in
      the subependymal layer, however the general organisation and cellular morphology
      of the adult human subependymal layer has not been demonstrated previously. In
      this study, we have demonstrated that the normal human brain subependymal layer
      contains three morphologically distinct types of cells, A, B and C type cells.
      The type A cells resembling migrating neuroblasts were located in the superficial
      part of the subependymal layer, type B cells resembling glial cells were evenly
      distributed throughout the subependymal layer and caudate nucleus, and type C
      cells that resembled progenitor cells were located in the deeper regions of the
      subependymal layer close to the caudate nucleus. We also examined the
      subependymal layer in the Huntington's disease brain to determine whether
      neurodegenerative pathology of the caudate nucleus (adjacent to the subependymal
      layer) altered the cellular composition of the subependymal layer. In the
      Huntington's disease subependymal layer there was a significant increase in the
      thickness of the subependymal layer compared with the normal subependymal layer
      (p < 0.01) and there was a 2.8-fold increase in the number of cells present in
      the Huntington's disease subependymal layer compared with the normal subependymal
      layer but the density of cells remained unchanged. As the grade of Huntington's
      disease increased, so did the overall number of cells in the subependymal layer.
      An increase in the number of type B cells was responsible for most of the
      increase demonstrated, however there was also an increase in the numbers of type
      A and C cells. To further characterise the human normal and Huntington's disease
      subependymal layer we used immunohistochemistry and antibodies against a range of
      projection neuron markers, interneuron markers, glial cell markers and GABAA
      receptor subunits. The results demonstrated the presence of increased numbers of
      neuropeptide Y positive cells in the Huntington's disease subependymal layer
      compared with the normal subependymal layer, suggesting that neuropeptide Y
      neurons may play a role in progenitor cell proliferation. Also there was an
      increased level of the developmentally active GABAA receptor subunit gamma 2 that
      indicates that the adult subependymal layer still retains the ability to
      proliferate. Taken together our results give a detailed description of the adult
      human subependymal layer and also demonstrate the plasticity of the human
      subependymal layer in response to Huntington's disease.

PMID- 16108101
TI  - Bupropion: seizures in an infant exposed through breast-feeding.
AB  - Bupropion (amfebutamone) enters maternal milk, with a potential risk of seizures
      in breast-feeding infants. Breast-feeding mothers should avoid the use of
      bupropion

PMID- 16108102
TI  - Paracetamol + dextropropoxyphene: planned withdrawal from the British market.

PMID- 16108103
TI  - Neuropsychiatric disorders on ibuprofen.

PMID- 16108104
TI  - Drotrecogin alfa: excess mortality in the least severely ill patients.

PMID- 16108106
TI  - [Urogynecology: Paris international in August].

PMID- 16108105
TI  - [Will publication of the French study E3N change prescription practices for
      hormone replacement therapy in menopausal women?].

PMID- 16108107
TI  - [Maternal obesity: effects on labor and delivery: Excluding other diseases that
      might modify obstetrical management].
AB  - AIMS: The aim of this survey was to analyze the effects on labor, delivery,
      afterbirth, and neonatal status of maternal obesity, independently of other
      diseases that might modify obstetrical management. POPULATION AND METHODS: Cross
      sectional survey of cases during one year in the obstetrics department of a
      university hospital center. The inclusion criterion was obesity, defined as BMI >
      30. The exclusion criteria were hypertension, pregnancy-related hypoxemia,
      diabetes (pre-existing or pregnancy-related), maternal cardio-pulmonary disease,
      uterine scar, multiple pregnancy, and non-cephalic presentation. Two groups, one
      obese and the other not, were matched for age and parity. RESULTS: The rate of
      post-term deliveries was higher among obese women (p = 0.04), induction of labor
      more frequent (p = 0.05), and the duration of its first phase longer (p = 0.003);
      the cesarean rate was seven times higher (14.6% versus 2.1%) and the mean weight
      of the newborns significantly higher (p = 0.01). Multivariate analysis found the
      following factors to be significantly associated with maternal obesity: longer
      duration of the first phase of labor, less frequent spontaneous vaginal delivery,
      higher cesarean rate, and higher rate of lack of progress in dilatation.
      CONCLUSION: This study shows that maternal obesity is a risk factor for
      complications during pregnancy, independently of its standard complications-
      pregnancy-related diabetes and hypertension. It compromises the smooth
      progression of labor and delivery. Pregnancy in obese women must be considered to
      be "at risk", regardless of any complications of obesity. It is thus important to
      help obese women become more aware of the importance of a balanced diet for
      themselves and their children. The presence of an obese adult in the household
      quadruples the risk of obesity in children.

PMID- 16108108
TI  - [Group B streptococcus in the antenatal clinic and in the delivery room: a matter
      of systematic attitude].
AB  - OBJECTIVES: We wanted to evaluate the compliance to the local recommendations,
      similar to the CDC (Centers for Disease Control and prevention) recommendations
      launched in 1996, for the prevention of perinatal group B streptococcal (GBS)
      disease in the clinical practice of a academic maternity and to identify the
      causes of missed screening and antibiotic prophylaxis. MATERIALS AND METHODS:
      Retrospective study of 1249 consecutive pregnancies between 1st January and 31th
      August 2002. The screening methods for GBS colonisation were the culture of
      rectovaginal swabs collected between 35 and 37 weeks and/or a rapid antigenic
      screening performed on a vaginal swab collected at the patient's admission for
      labor. RESULTS: Rate of global screening was very high (97.8%): 28.8% of
      antenatal screening versus 90.3% during labor. An appropriate antibiotic
      prophylaxis was administered to only one-third of positive women when the
      screening was performed at admission to the labor room, whereas two-thirds of GBS
      positive women screened between 35 and 37 weeks received their antibiotic
      prophylaxis. 2.4%o of the newborns were infected and 2.9% were colonized. Among
      the different risk factors, intrapartum fever was more often associated with
      maternal GBS colonisation. The observed sensitivity of the rapide antigenic test
      was 20.4%. CONCLUSION: Compliance to guidelines is sometimes difficult in the
      clinical practice of an academic maternity. In our hands the rapid test for GBS
      screening had low sensitivity. The analysis of these data led to introducing a
      computerized algorithm in our maternity to improve the prevention of perinatal
      group B streptococcal disease.

PMID- 16108109
TI  - [Changing medical practices and nosocomial infection rates in French maternity
      units from 1997 to 2000].
AB  - OBJECTIVES: In this study we describe the changes in medical practices and
      nosocomial infection rates in obstetrics observed through a surveillance network
      in the South East of France. MATERIAL AND METHOD: The maternity units which
      belong to this network participated in voluntary surveillance using the network's
      methodology. The criteria for the diagnosis of nosocomial infections were in
      accordance with the methods described by the Centers for Disease Control and
      Prevention. RESULTS: 101240 pregnancies including 18503 caesareans (18.3%) were
      included in the network from 1997 to 2000. During the study period, nosocomial
      infection rates following caesarean section and vaginal delivery decreased
      respectively from 7.8% to 4.3% (p < 0.001) and from 2.2% to 0.9% (p < 0.001).
      This evolution was compared with the evolution of collected risk factors.
      CONCLUSION: In spite of the methodology limits, general value of surveillance and
      infection control programs in maternity units has been confirmed by the results
      of this surveillance network. During the study period, both obstetrics-related
      risk factors for nosocomial infection and observed hospital-acquired infection
      rates were dramatically reduced, what prove an improvement of quality of care in
      maternity units.

PMID- 16108110
TI  - [Management of 103 limb reduction defects: a French-speaking fetal medicine club
      enquiry].
AB  - OBJECTIVES: Prenatal diagnosis of a limb reduction defect poses difficult medical
      and ethical problems. Prenatal diagnosis can be at the origin of two opposing
      medical attitudes, either a medical termination of pregnancy, or the specific
      management of the child at birth. The objective is to carry out an enquiry of
      practices and to determine whether there is a threshold in the gravity of the
      malformation from which the medical termination of pregnancy is accepted.
      MATERIAL AND METHOD: The study was carried out by a questionnaire addressed to
      the members of the French-speaking Club of Fetal Medicine. RESULTS: Outcome of
      103 fetuses with limb reduction defect was described. Prenatal diagnosis and
      management of observed malformations were explained. CONCLUSION: Decisions
      concerning the outcome of the pregnancy are very variable from one couple to
      another and from one medical team to another. Parents making a request must be
      given complete information and accompanying psychological support. Collegial with
      a multidisciplinary team is necessary. For the parents, it is the physician's
      duty to avoid judgement errors related to anxiety and ignorance of the medical
      consequences. The physician should guide the parents towards the continuation of
      the pregnancy or its interruption. The proper decision proceeds from the reunion
      of the confidence of the couple and the conscience of the physician.

PMID- 16108111
TI  - [Gestational trophoblastic diseases: a retrospective study from 1997 to 2003].
AB  - BACKGROUND: Trophoblastic diseases correspond to a very heterogeneous group of
      rare pathology in young women which fertility should be preserved. PATIENT AND
      METHODS: We conducted a retrospective study from 1997 to 2003, including all
      patients with molar pregnancy or trophoblatic tumor in our department of
      Obstetrics and Gynecology. RESULTS: Fifteen patients were identified with 9 molar
      pregnancies, 5 trophoblastic tumors and 1 placental tumor of implantation site.
      The outcome was favorable for 14, and one patient died from her metastatic
      disease. For 4 patients we asked our university colleague for the optimal
      approach. DISCUSSION: Management of molar pregnancies is well established.
      Persistent gestational disease is more rare and problematic with potential
      metastatic dissemination. Multidisciplinary care is often needed. CONCLUSION:
      Persistent gestational disease should be managed in a highly specialized centre,
      as developed in the Lyon University Hospital.

PMID- 16108112
TI  - [Ovarian cancer: incidence and mortality in France].
AB  - OBJECTIVES: To describe the ovarian cancer incidence and mortality trends in
      France from 1980 to 2000. MATERIALS AND METHODS: Incidence data were obtained
      from 9 French departments covered by cancer registries which systematically
      record all cancers, of which those of the ovary. Mortality data has been provided
      by INSERM bureau in charge of the analysis of death certificates. RESULTS: With
      4500 incident cases and 3500 deaths for the year 2000 in France, ovarian cancer
      still shows a poor prognosis. Age adjusted incidence and mortality rates are
      almost stable over the study period at an annual rate of 9 by 100000 for
      incidence and 5.5 by 100000 for mortality. However the risk of developing this
      cancer and the risk of dying from it, steadily decreased for the cohort born in
      1930 to 1950, and the beginning of this reduction corresponds exactly to the
      beginning of oral contraception. We present comparisons between departments and
      analyze the border-line tumors in parallel with invasive cancers. CONCLUSION: The
      cancer of the ovary represents only a small part of female cancers (3.8%) in
      France and its incidence is stable over time, but its prognosis is very bad.

PMID- 16108113
TI  - [Enterobiasis of the female pelvi-genital tract: a report of three cases].
AB  - Ectopic localization of oxyuriasis is rare and frequently does not cause clinical
      problems. It has been reported in the vagina, endometrium, fallopian tube,
      peritoneal surface and ovary; In these localizations it often causes pseudo
      tumoral granulomas. The aim of our study was to describe etiopathogenic and
      clinical criteria of this rare pathology. We report one case of endometrial
      enterobiasis which developed in a 28-year-old women and two cases of tubo-ovarian
      pseudotumoral abscesses containing the ova of enterobius which appeared as a
      latero-uterin mass in women aged 28 and 38 years. Enterobius vermicularis may
      cause tubo-ovarian abscess formation with necrotizing epitheloid granulomas
      mimicking tumors. Antihelminth therapies are successful.

PMID- 16108114
TI  - [Evaluation of search for human papillomavirus (HPV) during cervical precancer
      and cancer screening: synopsis and perspectives (May 2004)].

PMID- 16108115
TI  - [Evaluation of cytomegalovirus infection screening in pregnant women in France:
      synopsis and perspectives (September 2004)].

PMID- 16108116
TI  - [Red flag and Republic? Correspondence between P. Von Theobald, M. Cosson and J.
      Lansac following the editorials in the n 7-2004 issue of Journal de Gynecologie
      Obstetrique et Biologie de la Reproduction].

PMID- 16108117
TI  - [Evidence based medicine and secondary information sources].

PMID- 16108118
TI  - [Ovulation inducing drugs].

PMID- 16108119
TI  - Funding. Panel's HIV funding disappoints activists.

PMID- 16108121
TI  - Bias. Jury award reinstated in HIV discrimination case.

PMID- 16108120
TI  - NIAID funds center for HIV/AIDS vaccine immunology.

PMID- 16108122
TI  - Drug pricing. High price of Fuzeon, other recent drugs sets tough pricing
      precedent.

PMID- 16108123
TI  - Researchers explore cost-effective HIV preventions.

PMID- 16108124
TI  - Navy's testing order for civilians under review.

PMID- 16108125
TI  - Negligence claims fail in HIV-tainted transfusion case.

PMID- 16108126
TI  - Prisons. HIV-positive inmates in danger of treatment resistance.

PMID- 16108127
TI  - Global. Spouses' HIV status to be disclosed in Singapore.

PMID- 16108128
TI  - [Side effects of cellular and acellular DPT vaccine in children aged from 3
      months to 5 years].
AB  - INTRODUCTION: Both mild and severe local and systemic postvaccination reactions
      are seen more rarely in infants immunized with DTPa than in those immunized with
      DTPw vaccine. MATERIAL AND METHODS: By analysis of medical records and follow-up
      of patients, the authors serched for sings of adverse effects of DPT vaccines,
      comparing cellular and acelhular vaccines in children aged from three months to
      five years. The results of investigation were analyzed using X2. RESULTS: Out of
      the total number of 940 applied vaccines, 329 were cellular and 611 were
      acellular. Body temperature over 38.5 degrees C occurred in 3% of children
      immunized with cellular DTPw, and vomitting occurred in 0.8% of those immunized
      with acellular DTPa vaccine. Vomiting occurred (more than five times) in 0.9% of
      children immunized with DPTw and in 0.32% of children immunnized with DPTa. Other
      undesirable symptoms like swelling, redness and pain in the arm were found in
      0.6% of children immunized with DPTw, and in 0.32% of children immunized with
      DPTa; prolonged crying (three hours or longer) was registered in 0.3% of cases
      inzmmt- nized with DPTw, and in 0.16% of immunized with DPTa vaccine. Convulsions
      and collapse appeared only in 0.3% of children immunized with DPTw. DISCUSSION:
      Our investigation shows that local and generalized undesirable postvaccination
      reactions occurred in 5.4% of children immunized with DPTw and in 1.64 of
      children immunized with DPTa. The latest clinical investigations show that
      acellular pertussis vaccines are successful in prevention of pertussis and that
      they are quite safe for infants: in our investigations, local and generalized
      reactions were markedly rare in children immunized with DPTa. CONCLUSION:
      Undesirable postvaccinaition reactions after application of acellular DPT
      vaccines are less frequent than it is described in relevant references. The most
      frequent postvaccination reactions was raised body temperature (38.5 degrees C).
      Convulsions and collapses were not registered in children immnunized with DPTa
      vaccine. This investigation points to significantly rarer unwanted
      postvcaccinationl reactions of acellular DPT vaccine in comparison with DPTGw (p
      < 0.01).

PMID- 16108129
TI  - Helminth infections of children: prospects for control.

PMID- 16108131
TI  - [Outcome of psychotherapy].

PMID- 16108130
TI  - National cholesterol education program (NCEP) guidelines too complex.

PMID- 16108132
TI  - [Psychotherapy from the viewpoint of resources and affordance].

PMID- 16108133
TI  - [Description of psychoanalytic therapy in a manual form].

PMID- 16108134
TI  - [Relationship between psychoanalysis and Morita therapy--future trend in
      psychotherapy].

PMID- 16108135
TI  - [Essence of psychotherapy in respect to introspective therapy].

PMID- 16108136
TI  - [Re-evaluation of supportive psychotherapy].

PMID- 16108137
TI  - [Psychotherapy and drug therapy--drug therapy within the framework of
      psychotherapy and psychotherapy conducted during drug therapy].

PMID- 16108138
TI  - Drosophila bristles and the nature of quantitative genetic variation.
AB  - Numbers of Drosophila sensory bristles present an ideal model system to elucidate
      the genetic basis of variation for quantitative traits. Here, we review recent
      evidence that the genetic architecture of variation for bristle numbers is
      surprisingly complex. A substantial fraction of the Drosophila genome affects
      bristle number, indicating pervasive pleiotropy of genes that affect quantitative
      traits. Further, a large number of loci, often with sex- and environment-specific
      effects that are also conditional on background genotype, affect natural
      variation in bristle number. Despite this complexity, an understanding of the
      molecular basis of natural variation in bristle number is emerging from linkage
      disequilibrium mapping studies of individual candidate genes that affect the
      development of sensory bristles. We show that there is naturally segregating
      genetic variance for environmental plasticity of abdominal and sternopleural
      bristle number. For abdominal bristle number this variance can be attributed in
      part to an abnormal abdomen-like phenotype that resembles the phenotype of
      mutants defective in catecholamine biosynthesis. Dopa decarboxylase (Ddc) encodes
      the enzyme that catalyses the final step in the synthesis of dopamine, a major
      Drosophila catecholamine and neurotransmitter. We found that molecular
      polymorphisms at Ddc are indeed associated with variation in environmental
      plasticity of abdominal bristle number.

PMID- 16108139
TI  - Exhaled nitric oxide and asthma.

PMID- 16108140
TI  - Exhaled nitric oxide and asthma.

PMID- 16108141
TI  - Heart-rate profile during exercise as a predictor of sudden death.

PMID- 16108142
TI  - Coronary-artery bypass grafting versus stent implantation.

PMID- 16108143
TI  - Coronary-artery bypass grafting versus stent implantation.

PMID- 16108144
TI  - Asthma and invasive pneumococcal disease.

PMID- 16108145
TI  - Comparison of test devices for skin prick testing.
AB  - BACKGROUND: Allergy skin testing guides developing avoidance plans and writing an
      immunotherapy prescription. The goal for the allergist is to apply allergen skin
      testing to the appropriate patient population by using a device that minimizes
      both false-negative and false-positive findings while minimizing patient
      discomfort. New skin testing devices continue to be developed with a trend toward
      production of multiheaded devices. Data on the performance of these devices in a
      head-to-head prospective fashion are limited. OBJECTIVE: Our goal was to study 8
      commonly used devices to compare their performance in a head-to-head fashion.
      METHODS: In a prospective, double-blind fashion, the performance of 8 skin test
      devices was evaluated. Devices were tested with histamine and saline on both the
      arms and back of each subject. Devices were rotated over 4 testing sessions, at
      least a week apart, so each device was tested in each anatomic testing location.
      Performance elements examined included wheal, flare, pain, sensitivity,
      specificity, and intradevice variability. RESULTS: We found significant
      differences in all areas of device performance among all devices examined.
      Multiheaded devices also demonstrated significant intradevice variability and
      were more painful than single devices. Furthermore, multiheaded devices had
      larger reactions on the back, whereas single devices had larger reactions on the
      arms. CONCLUSION: Statistically significant differences exist among all devices
      tested. Providers should consider this data when choosing a device that suits
      their practice setting and ensure that technicians are sufficiently trained on
      the correct use of that device.

PMID- 16108146
TI  - [Kartagener].

PMID- 16108147
TI  - Asbestos and the future of mass torts.

PMID- 16108148
TI  - Evolutionary dynamics of altruism and cheating among social amoebas.
AB  - Dictyostelium discoideum is a eukaryotic amoeba, which, when starvation is
      imminent, aggregates to form fruiting bodies consisting of a stalk of
      reproductively dead cells that supports spores. Because different clones may be
      involved in such aggregations, cheater strategies may emerge that allocate a
      smaller fraction of cells to stalk formation, thus gaining a reproductive
      advantage. In this paper, we model the evolutionary dynamics of allocation
      strategies in Dictyostelium under the realistic assumption that the number of
      clones involved in aggregations follows a random distribution. By determining the
      full course of evolutionary dynamics, we show that evolutionary branching in
      allocation strategies may occur, resulting in dimorphic populations that produce
      stalkless and stalked fruiting bodies. We also demonstrate that such dimorphisms
      are more likely to emerge when the variation in the number of clones involved in
      aggregations is large.

PMID- 16108150
TI  - [WHO histological classification of ovarian tumors. Geneva, 1999 (R.E.Scully,
      L.H.Sobin].

PMID- 16108151
TI  - Adding RFID layer to blood safety loop.

PMID- 16108152
TI  - IMA lines up for place in cardiac triage.

PMID- 16108153
TI  - [Marketing and mortality with tobacco in front line].
AB  - Tobacco is an economical force. To make some people rich, by mankind paying the
      price, which--for years--count hundreds and hundreds of billions of dollars and
      millions of human lives. After 1990, in Romania tobacco plantation was not
      profitable anymore and as a consequence, we registered a diminution of tobacco
      cultivated surfaces, that reached 0.1% of total arable surface (in 1997 the
      lowest among similar surfaces in South-Eastern European countries). The original
      production of fermented tobacco decreased at the same rate. Cigarette consumption
      at the country level remains the same, the "supply" of cigarettes being assured
      by massive imports, under licensed production and smuggling. The mortality by
      different diseases due to smoking, is increasing progressively in the interval
      1997-2002. The increase rate of mortality by broncho-pulmonary neoplasm was 127%
      in men and 95.7% in women. In cerebrovascular diseases case the same indicator
      between 1998-2002 has values of 2.1% in men and 3.9% in women. The presentation
      of those gravity elements base the purpose of touching all the factors who
      complete in present to the application of individual and global strategies of
      smoking control in our country.

PMID- 16108154
TI  - [Induced sputum--means for detecting bronchial inflammation in children with
      atopic bronchial asthma and treatment monitoring].
AB  - Induced sputum is a very recent technique for exploration of bronchial
      inflammation in asthma. Since 1992, it has significantly improved as a method and
      as clinical and fundamental research tool for asthma. It is currently recognized
      that this method is well tolerated and can be used in all asthma patients, except
      those with FEV1 less than 11. Eosinophilic activation in asthma can be very well
      highlighted by cellular and biochemical analysis of expectoration. Thus, biologic
      arguments can be added to clinical signs in asthma exacerbations. Clinical
      evolution under corticosteroids can be biologically proved by this technique.
      Sputum analysis is useful also for differential diagnosis, sometimes difficult,
      between asthma and COPD.

PMID- 16108155
TI  - [Evolution of pulmonary metastasis in osteosarcoma].
AB  - Osteosarcomas are tumors with a high aggressivity which gives early and frequent
      pulmonary metastasis. These patients have a poor prognosis. The reveal of
      prognosis factors and early detection of pulmonary relapse would influence the
      outcome of these patients. We performed a retrospective study at Oncology
      Institute from Cluj, observing 35 patients with osteosarcomas and pulmonary
      metastasis at the onset or in evolution. We tried to quantify some prognosis
      factors. We observed the predominance of male sex (20), from urban area (25),
      with age between 11-20 years (16 cases), with primary tumors localized more
      frequently at the limbs. Pulmonary metastasis were shown without free interval
      from the onset (12 patients), or in the first years (17 cases), more frequently
      with multiples locations (26 cases). 28 patients were submitted to surgical
      treatment for cure of primary tumor, 18 chemotherapy, and pulmonary metastasis
      resection in 5 cases only. The outcome under treatment was favorable in 4 cases
      only, compared with other studies. Early detection of pulmonary metastasis and
      aggressive therapy with augmentation of resection criteria for pulmonary
      metastasis would improve the prognosis of this patients.

PMID- 16108156
TI  - [Etiology, diagnosis and therapeutic considerations in malignant pleural
      effusions].
AB  - Although its real incidence is not clearly established, malignant pleural
      effusions is one of the more common problems that internists, pneumologists and
      oncologists face in their daily practice. Because the patients are already
      terminally ill, it is important to obtain a diagnosis expeditiously and formulate
      a treatment plan that optimizes quality of life.

PMID- 16108157
TI  - [New therapeutic uses of the macrolides].

PMID- 16108158
TI  - [Controversy in the treatment of non-small cell lung cancer. Timing of
      chemotherapy in relation to surgery: before or after?].

PMID- 16108159
TI  - [Elemental mercury embolism in the lung].
AB  - Elemental mercury embolism to the lung - a case report A case of deliberate
      parenteral self-injection of elemental mercury in a drug-addict 18 years old man
      is presented. Chest x-ray films showed mercury deposits in the lungs, as well as
      around the injection site. At follow-up at 2 years, he was well, with none of the
      renal, gastrointestinal, or neurologic effects that can result from the oxidation
      of mercury. The clinical and radiological course of the patient is described.

PMID- 16108160
TI  - [Oxygen inhalation therapy in COPD exacerbations].

PMID- 16108161
TI  - [Multiple bilateral nodular opacities and bilateral pleural effusion].

PMID- 16108162
TI  - [Smoking and its relation to poverty].

PMID- 16108163
TI  - [Gastroesophageal reflux in asthmatic children: prevalence and pathogenic role].
AB  - The relationship of gastroesophageal reflux disease and asthma is controversial.
      This study was performed to assess the prevalence of pathologic gastroesophageal
      reflux and its effect on pulmonary function tests in asthmatic children. The
      following study protocol was performed in a group of asthmatic children (n = 34,
      22 male, age range: 2, 5-17 years): diagnosis of pathologic gastroesophageal
      reflux by means of 24h esophageal pH-monitoring; diagnosis of reflux esophagitis
      by means of upper digestive endoscopy and pulmonary function tests by means of
      spirometry. The results show a high prevalence (87%) of pathologic
      gastroesophageal reflux in asthmatic children. Additionally, there is an inverse
      correlation (r = -0.67) between the severity of pathologic gastroesophageal
      reflux and FEV1/FVC. In conclusion, there is a high prevalence of pathologic
      gastro-esophageal reflux in asthmatic children, contributing to asthma severity.

PMID- 16108164
TI  - Liver transplantation in the Asia Pacific region--trials and tribulations.

PMID- 16108165
TI  - Advances in portal hypertension.

PMID- 16108166
TI  - Spontaneous bacterial peritonitis [SBP].

PMID- 16108167
TI  - Infections in patient with decompensated cirrhosis.

PMID- 16108168
TI  - Hepatorenal syndrome.

PMID- 16108169
TI  - Chronic hepatitis B--treatment with nucleoside analogues.
AB  - Nucleot(s)ide analogues are making milestones in the treatment of chronic
      hepatitis B (CHB) as safe oral therapy. FDA approved lamivudine in adult patients
      in 1998, adefovir dipivoxil in 2002, and entecavir in March 2005. Lamivudine is
      effective in viral suppression, ALT normalization, and improvement in histology
      in both HBeAg positive and HBeAg negative / HBV DNA positive patients. HBeAg
      seroconversion rates correlate directly with pretreatment ALT levels at 18-30%
      after one year of therapy. Hepatitis flares may occur if lamivudine is stopped
      before HBeAg seroconversion. Lamivudine resistant YMDD mutants emerge at a rate
      of 15-20% per year of therapy; often associated with the rebound viraemia,
      relapse of hepatitis or even hepatic decompensation. Durability of response off
      lamivudine therapy is not satisfactory and may be dependent on duration of
      therapy post-seroconversion. Lamivudine is well tolerated with few serious
      adverse events, even in patients with decompensated cirrhosis. Long term therapy
      in viraemic patients with advanced fibrosis or cirrhosis delays clinical
      progression. Adefovir dipivoxil is an oral prodrug of adefovir. 10 mg daily is
      effective in suppressing both wild-type HBV and YMDD mutants, normalising ALT and
      improving histology. Adefovir dipivoxil has been shown to be well tolerated in
      longterm therapy. Renal toxicity reported in higher dosages is rarely seen except
      among patients with creatinine clearance less than 50 ml/min. Adefovir resistance
      may emerge and the overall rate is much lower than lamivudine, reaching 18% after
      4 years of therapy. Adefovir-resistant mutants (rt N236T) are susceptible to
      lamivudine and entecavir. Little data is available for durability of response off
      therapy. Entecavir is an oral nucleoside analogue with a recommended dosage of
      0.5 mg daily for nucleoside-naive patients, and 1 mg daily for lamivudine
      refractory patients. It is a potent antiviral and may also reduced intrahepatitic
      cccDNA. Entecavir resistance so far has only been detected in lamivudine
      resistant patients in the one-year studies. Patient counseling is very important
      to decide on the choice among available therapeutic options. The assessment of
      the risks/benefits of each option should be carefully explained to individual
      patient.

PMID- 16108170
TI  - Treatment of chronic hepatitis B infection using interferon.
AB  - Four to 6 months of conventional interferon alpha (IFN-alpha) (5MU daily or 10MU
      three times weekly) resulted in HBeAg loss in approximately 33% of HBeAg positive
      patients (controls: 12%). Longer treatment duration improved HBeAg
      seroconversion. Children with chronic HBV infection and high ALT respond to IFN-a
      at similar rates. Good end-of-treatment (ET) biochemical and virological response
      were also achieved with IFN-alpha in HBeAg negative, HBV-DNA positive hepatitis
      patients. Sustained response (SR) however, was disappointing, but improved with
      longer duration of treatment: (10-15% SR with 4/6 months treatment: 30% SR with
      24 months treatment). Weekly pegylated IFN-alpha2a (PegIFN-alpha2a) for 24 weeks
      gave a significantly higher HBeAg conversion rate (33%) than conventional IFN
      alpha2a (25%). Fifty-two weeks of PegIFN-alpha2b gave a sustained HBeAg loss in
      35% patients and HBeAg seroconversion in 29% patients. Similar results were
      obtained with 48 weeks of weekly PegIFN-alpha2a. PegIFN-alpha2a monotherapy was
      found to be superior to lamivudine monotherapy in affecting a 6-month SR (normal
      ALTs and HBV DNA < 20,000 copies/mL) in HBeAg negative/anti-HBe positive chronic
      hepatitis B patients. There is a tendency for IFN-a and lamivudine combination to
      result in better sustained response than lamivudine monotherapy. This tendency is
      also observed with PegIFN-a and lamivudine combination although the combination
      did not appear to be better than PegIFN-alpha monotherapy. IFN induced HBeAg
      seroconversion is durable, could increase over time and resulted in better
      overall survival and survival free of hepatic decompensation or hepatocellular
      cancer. The main advantage of IFN-a therapy is that a course of finite duration
      may achieve sustained off-therapy response in a proportion of both HBeAg positive
      and HBeAg negative chronic hepatitis B patients. However, IFN treatment is
      usually associated with side-effects, especially flu-like symptoms, fatigue,
      neutropenia, thrombocytopenia and depression. These are usually tolerable but may
      require dose modification and premature cessation of treatment (5%). Interferon
      therapy induced hepatitis flares may lead to decompensation in patients with
      cirrhosis and can be dangerous in patients with decompensated liver function
      despite dose reduction.

PMID- 16108171
TI  - Chronic hepatitis B and herbal therapy.

PMID- 16108172
TI  - Surrogate markers for liver fibrosis.

PMID- 16108173
TI  - Interpretation and application of virological testing including resistance in
      chronic hepatitis B.

PMID- 16108174
TI  - Treatment of chronic hepatitis B in HIV co-infected patients.
AB  - In the Asia Pacific region Human Immunodeficiency virus (HIV) is often acquired
      in individuals already infected with hepatitis B virus (HBV). The immune
      suppression caused by HIV infection reduces cellular immune response against HBV
      and liver inflammation may improve, but the risk of developing cirrhosis is not.
      HBV infection does not affect the progression of HIV disease. Anti-retroviral
      agents may be directly hepatotoxic and cause ALT elevations in patients with
      chronic hepatitis. Highly active anti-retroviral therapy (HAART) improves
      immunity and as cytotoxic lymphocyte responses improve, hepatitis flares can
      occur, usually r within 3 months of initiation of HAART. These hepatitis flares
      may be followed by normalization of ALT and clearance of HBVDNA. If lamivudine is
      included in the HAART regime, hepatitis flares may not occur till late and these
      late flares signal the development of lamivudine resistant HBV strains (90% of
      HBV/HIV co-infection). Treatment options for chronic HBV infection include
      interferon (IFN), and nucleoside analogues. Lamivudine, adefovir dipivoxil,
      tenofovir disoproxil fumarate (DF) are nucleoside analogues with activity against
      both HBVDNA polymerase and HIV reverse transcriptase. The latter two compounds
      have added activity against lamivudine resistant HBVDNA. Lamivudine should be
      avoided in the initial treatment of both hepatitis B as well as HIV because of
      the high incidence of resistance. Interferon should be considered first for
      treatment of HBV in HIV co-infected individuals and is usually unsuccessful in
      the later stages of HIV infection when immune suppression is extreme. As new and
      improved agents in HAART continue to prolong survival, the use of liver
      transplantation for cirrhotic patients co-infected with HIV and HBV may increase.

PMID- 16108175
TI  - Treatment of immunosuppressed chronic hepatitis B patients.

PMID- 16108176
TI  - HBV and liver cancer.
AB  - The association of hepatitis B virus (HBV) infection and liver cancer is well
      documented in epidemiological study. Patients with chronic hepatitis B have
      increased risk of hepatocelluar carcinoma (HCC), in particular those with active
      liver disease and cirrhosis. The incidence of HCC increases with age and is more
      common among male patients. The introduction of universal HBV vaccination program
      for the newborn in endemic regions has started to show beneficial impact. Taiwan
      introduced this program two decades ago and the incidence of liver cancer among
      infants and young children have declined significantly. The carcinogenic events
      leading to HCC are under intense research. A number of hypotheses have been
      proposed. HBV is not directly hepatotoxic but its interaction with the host
      immune system creates opportunity for HBV DNA integration into the host genome.
      One of the main foci of research is the HBX-encoded X protein. Its integration
      and protein expression impose alteration in cell proliferation cycle and
      apoptosis process. Many other factors may be involved including viral-induced
      alterations in p53 and telemerase, HBV genotypes, co-infection with HCV or delta
      agents, patient's lifestyle such as smoking, alcohol excesses, and genetic
      factors of the host patient. The processes of necroinflammation, cell
      proliferation and fibrosis facilitate the initial carcinogenic development. HCC
      surveillance with tumor markers such as alpha-foetal protein, decarboxylated
      prothrombin, in conjunction with imaging techniques has identified early small
      HCC that is amenable to curative therapy. Viral load has been correlated with
      increase risk of HCC. The available anti-viral agents have demonstrated clinical
      benefit among those with maintained and sustained response. Interferon and
      lamivudine therapy have demonstrated reduction of HCC among responders. However,
      they only constitute a minority proportion of treated patients. The mainstay of
      prevention should lie in prevention of HBV infection and early effective therapy
      of chronic hepatitis B infection.

PMID- 16108177
TI  - Managing liver metastases: myth or reality?

PMID- 16108178
TI  - Management of patients coinfected by HCV and HIV.

PMID- 16108179
TI  - Treatment of chronic hepatitis C in patients with renal disease.

PMID- 16108180
TI  - Management of treatment non responders in chronic hepatitis C.

PMID- 16108181
TI  - EUS and hepatobiliary disease.

PMID- 16108182
TI  - Liver transplantation--patient selection and timing.
AB  - Liver transplantation has been successfully used in the treatment of a large
      number of liver diseases. The largest patient group comprises patients with end
      stage decompensated liver disease. Decompensation is defined as the presence of
      cirrhosis and one or more of the following: jaundice, ascites, hepatic
      encephalopathy, hepatorenal syndrome or bleeding oesophageal varices. In general
      patients in this category should be considered for liver transplantation, if
      available. Guidelines for liver transplant assessment have been published by both
      the British Society of Gastroenterology and the American Association for the
      Study of Liver Disease. These guidelines provide a good basis for patient
      selection. As new information becomes available the indications for individual
      diseases may change somewhat. One of the most important changes in recent years
      was the introduction of the MELD/PELD scoring system. This is the model for end
      stage liver disease which provides a reasonably robust estimate of prognosis for
      individual patients. Prior to this patient waiting time on the transplant list
      was one of the principal determinants of priority for liver allocation. The MELD
      scoring system has been widely adopted with the aim of allocating the available
      livers to patients in the greatest clinical need.

PMID- 16108183
TI  - Liver transplantation in chronic hepatitis B.

PMID- 16108184
TI  - Liver transplantation in children.

PMID- 16108185
TI  - Chronic pancreatitis: aetiology, epidemiology and clinical presentation.
AB  - Chronic pancreatitis is a difficult disease to treat. Worldwide, alcohol is the
      most common aetiology but based on recent studies it is clear that genetic
      susceptibility plays an important role in determining disease. Several important
      genetic mutations have been identified. The prevalence of chronic pancreatitis
      appears to be lower in Asia although very high rates have been reported in parts
      of India. Severe intractable pain is the predominant presenting complaint of
      patients. The natural history of the disease and the onset of exocrine and
      endocrine insufficiency depend on the classification of disease as early onset,
      late-onset or alcohol associated. Complications of chronic pancreatitis are
      important and include pseudocyst formation, bile duct and duodenal strictures.

PMID- 16108186
TI  - Calcific pancreatitis: the Indian plague.

PMID- 16108187
TI  - Pseudocyst and cystic lesions of the pancreas--a diagnostic dilemma.

PMID- 16108188
TI  - Approach to the treatment of primary liver cancer.

PMID- 16108189
TI  - Non-surgical options in the management of hepatocellular carcinoma.

PMID- 16108190
TI  - Hepatitis A vaccines.
AB  - Hepatitis A, an acute usually self limiting infection of the liver is one of the
      most common vaccine-preventable infectious disease in the world. Effective
      vaccines which provide long term immunity against hepatitis A have been available
      since 1992. They are of known good quality, well tolerated with no serious
      adverse events and have been successfully used to protect different populations
      from infection as well as interrupt outbreak in closed communities. Mathematical
      models estimate the long term persistence of antiHAV antibodies to be more than
      25 years. Vaccination efforts should be supplemented by health education and
      improved sanitation. Planning for large scale immunization programmes against
      hepatitis A should take into consideration epidemiological and cost benefit
      studies.

PMID- 16108191
TI  - Hepatitis C and hepatitis E vaccines: research update.

PMID- 16108192
TI  - Aetiology and classification of acute liver failure.

PMID- 16108193
TI  - Acute liver failure--current approach to treatment.

PMID- 16108194
TI  - Extracorporeal liver support and the role of liver transplantation.

PMID- 16108195
TI  - Autoimmune hepatitis.

PMID- 16108196
TI  - Gall bladder cancer.

PMID- 16108197
TI  - ERCP induced complications.

PMID- 16108198
TI  - Bile duct injury.

PMID- 16108199
TI  - Hepatobiliary practical: how to get the best out of a liver biopsy.
AB  - The liver biopsy has a unique place in the investigation of liver disease because
      the concepts and classification of liver disease are rooted in morphology. Today,
      the use of the liver biopsy has extended beyond that of diagnosis, to the
      assessment of disease progression, response to therapy and transplant rejection.
      To get the best out of the liver biopsy, it is necessary to appreciate the
      usefulness and limitations of the biopsy specimen. Aspects to consider include:
      (1) minimizing sampling errors, and appreciating that the changes in the biopsy
      may not be representative of the primary pathology, (2) good laboratory quality
      practices to avoid processing artifacts, which may render a biopsy undiagnosable,
      (3) the appropriate use of special stains and other laboratory techniques, (4)
      adoption of a systematic and algorithmic approach in the microscopic examination
      of the biopsy, and (5) good clinicopathological correlation.

PMID- 16108200
TI  - Passing the torch.

PMID- 16108201
TI  - Tainted blood and vengeful spirits: the legacy of Japan's yakugai eizu (AIDS)
      trial.
AB  - Medical anthropologists often point to the importance of "illness narratives" as
      emergent or incipient forms in which patients attempt to make sense of the moral
      dimensions of illness and suffering (Kleinman 1988; Mattingly 1998). In this
      article I draw upon published accounts, newspapers, and legal documents,
      supplemented by ethnographic interviews carried out from 1999 to 2001, to show
      how plaintiffs in the yakugai AIDS trials brought by HIV-infected hemophiliacs
      against the Japanese government and the pharmaceutical industries that sold them
      tainted blood products appropriated powerful cultural themes in producing
      narrative accounts of their suffering. These narratives resonate with themes of
      lost trust, filial piety, and the desire for a "good death." In contrast, I show
      how the neat and tidy narrative that emerged in the course of the yakugai AIDS
      trial served to impose meaning upon the plaintiffs' unruly experiences such that,
      when it was over, the Japanese public was convinced that the "AIDS problem" had
      been "solved."

PMID- 16108202
TI  - Accusations of genital theft: a case from northern Ghana.
AB  - Occurrences of panic attacks associated with belief in genital retraction have
      been described in the anthropological and psychological literature in terms of
      culture bound reactive syndromes. Similar phenomena occur widely in West Africa,
      where they are reported as cases of penis snatching. Explanations for these
      phenomena range from the biomedical emphasis on pathology to the social
      psychological emphasis on altered perceptual sets. This paper provides a
      narrative of an accusation of genital theft in a rural West African settlement.
      Drawing from ethnographic information, it will be argued that the case is best
      explained in light of social relations, definitions for in-groups and out-groups,
      and local knowledge concerning witchcraft and divination. Local explanations for
      the case conform to both biomedical and social psychological models.

PMID- 16108203
TI  - Understanding genital-shrinking epidemics in West Africa: koro, juju, or mass
      psychogenic illness?
AB  - A small-scale epidemic of genital shrinking occurred in six West African nations
      between January 1997 and October 2003. This article presents a summary and
      analysis of 56 media reports of these cases. A clinical formulation of these
      cases considers a variety of explanations from theory and research in social and
      cultural psychology, psychopathology, and anthropology. Of particular interest is
      a comparison of genital-shrinking distress in West African settings with koro, a
      culture-bound syndrome involving fears of genital retraction that is prominent in
      Southeast Asian settings. The paper concludes with a brief discussion of the role
      of culture in both the experience of genital-shrinking distress and conceptions
      of psychopathology.

PMID- 16108204
TI  - Scoring men: vasectomies and the totemic illusion of male sexuality in Oaxaca.
AB  - This paper discusses research on men's reproductive health and sexuality in
      Oaxaca, Mexico, and specifically why some men there choose to be sterilized. Men
      who opt for vasectomies do so after considering numerous cultural, historical,
      physiological, commercial, and other concerns. Men and women in Oaxaca negotiate
      certain cultural folk beliefs about supposed male sexual desires and practices
      before arriving at the decision to get the operation. Vasectomy as a method of
      birth control is chosen despite folk beliefs that take the form of a totemic
      illusion which treats male sexuality as naturalized, something fixed, and as
      entirely distinct from female sexuality. Among its many consequences, this
      totemic illusion serves to conceal inequalities in the sphere of reproductive
      health and sexuality in relation to contraception.

PMID- 16108205
TI  - Family perceptions of prognosis, silence, and the "suddenness" of death.
AB  - Studies of end-of-life communication and care have emphasized physician-patient
      conversations, often to the exclusion of family members' discussions and
      interactions with providers, or with patients themselves. Relatively little is
      known therefore about families' experiences of end-of-life care in the hospital,
      or the concrete meanings and practices through which families conceive and define
      communication. Yet increasingly, family members are asked to serve as surrogates
      and thereby to participate in the facilitation of decisions for medical
      procedures and the withdrawal of treatments. It is thus worthwhile to consider
      their perceptions and involvement in hospitalization at the end of life. This
      paper offers a descriptive account of families' assessments of communication at
      life's end in the hospital--focusing in particular on their understandings of and
      conversations about prognosis and its implications. It reflects on the burdens of
      responsibility and regret posed to families by the ways communication is both
      conceived and evaded by different players in the hospital setting.

PMID- 16108206
TI  - Weak kidney and panic attacks in a traumatized Vietnamese male.

PMID- 16108207
TI  - Pregnancy rates in repeat-breeder heifers following multiple artificial
      inseminations during spontaneous oestrus.
AB  - Hormonal asynchronies during oestrus, related to the presence of suprabasal
      plasma-progesterone (P4) concentrations and a delayed ovulation, interfere with
      the fertility of repeat-breeder heifers (RBH). Since tubal dysfunction can occur
      in connection with hormonal asynchronies and constrained availability of fertile
      spermatozoa at the time of ovulation, the present study tested the hypothesis
      that frequent sperm deposition from onset of oestrus to ovulation may improve
      pregnancy rates in RBH. Five RBH and five virgin heifers (VH; controls) were
      repeatedly artificially inseminated (AI) at 6 h intervals from onset of oestrus
      to spontaneous ovulation. Hormone analyses revealed suprabasal P4 concentrations
      and a delay in the occurrence of the luteinising hormone (LH) surge, but a normal
      cortisol profile in RBH. Compared with controls, RBH presented longer interval
      from onset of oestrus to ovulation, and therefore, received more AIs. Pregnancy
      rates in RBH reached control levels (60%; NS), indicating that the hypothesis
      might be correct. Pregnancy rates in VH were below the expected range, presumably
      attributed to a deleterious influence of the frequent handling. The study
      suggests that pregnancy rates can be improved in RBH by frequent AI in relation
      to spontaneous ovulation. However, this practice of repeated manipulations, while
      seeming not to show adverse effects, lacks practicality for routine use.

PMID- 16108208
TI  - IS900 restriction fragment length polymorphism (RFLP) analysis of Mycobacterium
      avium subsp. paratuberculosis isolates from goats and cattle in Norway.
AB  - In Norway, paratuberculosis has been frequently diagnosed in goats, while cattle
      have been almost free of the infection. This difference in prevalence between
      goats and cattle has led to speculations about the existence of a Mycobacterium
      avium subsp. paratuberculosis (M. a. paratuberculosis) isolate that is non
      pathogenic for cattle. There is little information available on genotypic
      variation of M. a. paratuberculosis isolated from animals in Norway. In the
      present study, genotypic information on 51 isolates from goats and four isolates
      from cattle in Norway was obtained by use of IS900 restriction fragment length
      polymorphism (RFLP) analysis. All isolates from cattle and 84% of the isolates
      from goats had the same RFLP pattern (B-C1). Five RFLP patterns not previously
      detected were found. No genotypic variation that could explain a difference in
      host origin was found between the isolates from cattle and the majority of the
      Norwegian goat isolates. This lack of difference indicates that the most common
      M. a. paratuberculosis isolates in Norway may infect both cattle and goats.

PMID- 16108209
TI  - Is snow a sufficient source of water for horses kept outdoors in winter? A case
      report.
AB  - Due to extreme weather conditions, a flock of outwintered Icelandic horses had to
      manage for several days on snow as the source of free water. They were fed grass
      silage ad lib, and any change in feed consumption was not observed. After nine
      days, blood samples were taken and analysed for plasma osmolality, they were
      subjected to a simple clinical examination, and offered drinking water.
      Osmolality levels were within normal limits and mean value did not differ
      significantly from samples which previously were taken of the same individuals.
      The general condition of the horses was normal, with no signs of clinical
      dehydration or disease. The horses showed very little interest for the offered
      drinking water. This suggests that in cold winter weather, horses being fed grass
      silage and adjusted to eat snow, can manage for several days with snow
      substituting liquid water without their physiology and welfare being challenged.

PMID- 16108210
TI  - Campylobacter spp., Salmonella spp., verocytotoxic Escherichia coli, and
      antibiotic resistance in indicator organisms in wild cervids.
AB  - Faecal samples were collected, as part of the National Health Surveillance
      Program for Cervids (HOP) in Norway, from wild red deer, roe deer, moose and
      reindeer during ordinary hunting seasons from 2001 to 2003. Samples from a total
      of 618 animals were examined for verocytotoxic E. coli (VTEC); 611 animals for
      Salmonella and 324 animals for Campylobacter. A total of 50 samples were
      cultivated from each cervid species in order to isolate the indicator bacterial
      species E. coli and Enterococcus faecalis / E. faecium for antibiotic resistance
      pattern studies. Salmonella and the potentially human pathogenic verocytotoxic E.
      coli were not isolated, while Campylobacter jejuni jejuni was found in one roe
      deer sample only. Antibiotic resistance was found in 13 (7.3%) of the 179 E. coli
      isolates tested, eight of these being resistant against one type of antibiotic
      only. The proportion of resistant E. coli isolates was higher in wild reindeer
      (24%) than in the other cervids (2.2%). E. faecalis or E. faecium were isolated
      from 19 of the samples, none of these being reindeer. All the strains isolated
      were resistant against one (84%) or more (16%) antibiotics. A total of 14 E.
      faecalis-strains were resistant to virginiamycin only. The results indicate that
      the cervid species studied do not constitute an important infectious reservoir
      for either the human pathogens or the antibiotic resistant microorganisms
      included in the study.

PMID- 16108211
TI  - Endocrine and ovarian changes in response to the ram effect in
      medroxyprogesterone acetate-primed Corriedale ewes during the breeding and
      nonbreeding season.
AB  - Two experiments were performed to determine the endocrine and ovarian changes in
      medroxyprogesterone acetate (MAP)-primed ewes after ram introduction. Experiment
      1 was performed during the mid-breeding season with 71 ewes primed with an
      intravaginal MAP sponge for 12 days. While the control (C) ewes (n = 35) were in
      permanent contact with rams, the ram effect (RE) ewes (n = 36) were isolated for
      34 days prior to contact with rams. At sponge withdrawal, all ewes were joined
      with eight sexually experienced marking Corriedale rams and estrus was recorded
      over the next 4 days. The ovaries were observed by laparoscopy 4-6 days after
      estrus. Four weeks later, pregnancy was determined by transrectal
      ultrasonography. In eight ewes from each group, ovaries were ultrasonographically
      scanned; FSH, LH, and estradiol-17beta were measured every 12 hours until
      ovulation or 96 hours after estrus. The response to the rams was not affected by
      the fact that ewes had been kept or not in close contact with males before
      teasing. No differences were found in FSH, LH, estradiol-17beta concentrations,
      growth of the ovulatory follicle, onset of estrus, ovulation rate, or pregnancy
      rate. Experiment 2 was performed with 14 ewes during the nonbreeding season. Ewes
      were isolated from rams for 1 month, and received a 6-day MAP priming. Ovaries
      were ultrasonographically scanned every 12 hours, and FSH, LH, estradiol-17beta,
      and progesterone were measured. Ewes that ovulated and came into estrus had
      higher FSH and estradiol-17beta levels before introduction of the rams than did
      ewes that had a silent ovulation. The endocrine pattern of the induced follicular
      phase of ewes that came into estrus was more similar to a normal follicular
      phase, than in ewes that had a silent ovulation. The follicle that finally
      ovulated tended to emerge earlier and in a more synchronized fashion in those
      ewes that did come into estrus. All ewes that ovulated had an LH surge and
      reached higher maximum FSH levels than ewes that did not ovulate, none of which
      had an LH surge. We conclude that (a) the effect of ram introduction in cyclic
      ewes treated with MAP may vary depending on the time of the breeding season at
      which teasing is performed; (b) patterns of FSH, and estradiol-17beta
      concentrations, as indicators of activity of the reproductive axis, may be used
      to classify depth of anestrus; and (c) the endocrine pattern of the induced
      follicular phase, which is related to the depth of anestrus, may be reflected in
      the behavioral responses to MAP priming and the ram effect.

PMID- 16108212
TI  - Description of the infection status in a Norwegian cattle herd naturally infected
      by Mycobacterium avium subsp. paratuberculosis.
AB  - The Norwegian surveillance and control programme for paratuberculosis revealed 8
      seroreactors in a single dairy cattle herd that had no clinical signs of
      Mycobacterium avium subsp. paratuberculosis (M. a. paratuberculosis) infection.
      Paratuberculosis had been a clinical problem in goats several years previously in
      this herd. All 45 cattle were culled and a thorough investigation of the
      infection status was conducted by the use of interferon-gamma (IFN-gamma)
      immunoassay, measurement of antibodies, and pathological and bacteriological
      examination. In the IFN-gamma immunoassay, 9 animals gave positive results, and
      13 were weakly positive, while 19 animals were negative. In the serological test,
      10 animals showed positive reactions, and 5 were doubtful, while 30 animals gave
      negative reactions. There appeared to be a weak trend toward younger animals
      having raised IFN-gamma and older animals having raised serological tests.
      Histopathological lesions compatible with paratuberculosis were diagnosed in 4
      animals aged between 4 and 9 years. Three of these animals had positive
      serological reaction and one animal gave also positive results in the IFN-gamma
      immunoassay. Infection was confirmed by isolation of M. a. paratuberculosis from
      2 of these 4 animals. One single bacterial isolate examined by restriction
      fragment length polymorphism (RFLP) had the same profile, B-C1, as a strain that
      had been isolated from a goat at the same farm several years previously. Despite
      many animals being positive in one or both of the immunological tests, indicative
      of a heavily infected herd, none of the animals showed clinical signs and only
      one cow was shown to be shedding bacteria. A cross-reaction with other
      mycobacteria might have caused some of the immunoreactions in these animals. It
      is also possible that the Norwegian red cattle breed is resistant to clinical
      infection with M. a. paratuberculosis.

PMID- 16108213
TI  - Stratification, blinding and placebo effect in a randomized, double blind placebo
      controlled clinical trial of gold bead implantation in dogs with hip dysplasia.
AB  - The purpose of this study was to investigate the need for and choice of
      stratification factors, and the effects of blinding and placebo in a clinical
      experiment. Eighty dogs with canine hip dysplasia (CHD) were included in a
      randomized, placebo-controlled and double blind clinical trial with stratified
      parallel group design, in which body weight and degree of CHD were used as
      stratification factors. Thirty-eight dogs were allocated to gold bead
      implantation and 42 to placebo. After six months, 33 of the 42 placebo-treated
      dogs received gold bead implantation in an open study lasting a further 18
      months. The main outcome variable in the study was change in pain signs of CHD as
      assessed by the owner. No significant difference in the main outcome variable,
      regardless of the treatment given, could be detected in the two chosen
      stratification factors. The only factor to influence the main outcome variable
      significantly was age. The blinding procedure used in the study, in which 60% of
      the owners correctly guessed the treatment given, was found sufficient. Of those
      who guessed the treatment erroneously, 88% believed the treatment given was gold
      bead implantation. The treatment efficacy after six months in the blinded
      treatment group was found to be significantly larger compared to the efficacy
      obtained in the open study. A significant placebo effect was therefore detected.
      CONCLUSION AND CLINICAL RELEVANCE: The age of the dogs influenced the outcome of
      the CHD treatment, and is recommended as a stratification factor. A significant
      placebo effect has to be expected and an optimal blinding procedure is necessary
      in similar clinical studies.

PMID- 16108214
TI  - An investigation of the ability of the glutaraldehyde test to distinguish between
      acute and chronic inflammatory disease in horses.
AB  - The glutaraldehyde test (GT), a rapid and inexpensive test, has been utilized
      empirically for many years in bovine practice for diagnosing inflammatory
      diseases. GT is used primarily to demonstrate increased serum concentrations of
      fibrinogen and globulin. Glutaraldehyde binds with free amino groups in
      fibrinogen and immunoglobulin to create a clot in a first degree chemical
      reaction. The clotting time of the GT estimates the content of proteins produced
      in response to inflammation. The applicability of GT for diagnosing inflammation
      in the horse has never been investigated. The objective of this study was to
      determine the ability of GT to distinguish between acute and chronic inflammatory
      disease in horses. Thirty-seven horses with suspected inflammatory diseases were
      evaluated using the GT, history, complete clinical examination and routine blood
      analysis. GT-times, laboratory results and clinical outcome were compared
      statistically. Horses that were determined to be acutely affected (based on
      history, clinical examination and routine blood analysis) tended to have a
      negative GT (75%). Results of the GT did not correlate with blood fibrinogen
      concentration. Positive GT also predicted a fatal outcome in 69% of the clinical
      cases. The results of this trial indicate that GT can be a useful screening test
      to distinguish between acute and chronic inflammatory disease in horses.

PMID- 16108215
TI  - Surgical decompression in dogs with thoracolumbar intervertebral disc disease and
      loss of deep pain perception: A retrospective study of 46 cases.
AB  - The case details and outcome after surgical decompression of 46 dogs with
      thoracolumbar intervertebral disc disease with loss of deep pain perception prior
      to surgery were reviewed. Nineteen dogs (41.3%) recovered with a median follow-up
      period of 12.5 months. Recovery was defined as an ambulatory paraparesis, or
      better, with urinary and fecal continence. There was a better outcome in dogs
      with loss of deep pain for less than 24 hours prior to surgery (19/41; 46.3%
      recovered) than in dogs without deep pain perception for more than 24 hours (0/5;
      0% recovered). Dogs with deep pain perception present at two weeks
      postoperatively had significantly higher success rate (8/12; 66.7% recovered)
      than dogs without deep pain perception at this time period (1/10; 10.0%
      recovered). The return of deep pain perception by two weeks postoperatively can
      be a useful positive prognostic indicator.

PMID- 16108217
TI  - An investigation of salmonella bacteria in waterfowls and migratory birds in
      Norway.

PMID- 16108216
TI  - Prescribing antimicrobial agents for dogs and cats via university pharmacies in
      Finland--patterns and quality of information.
AB  - The aim of our study was to evaluate antimicrobial use in dogs and cats in
      Finland. Information on veterinary prescriptions was gathered from University
      Pharmacies (n=17) over a one-month period, April 2001. A total of 2719
      prescriptions for veterinary use were delivered, of which the majority were for
      dogs (70%, n=1898) and cats (14%, n=384). The most prescribed therapy group was
      per-oral antimicrobial agents (53%, n=1449), of which 16% (n=237) were medicines
      approved for humans. The most commonly used substances for dogs and cats were
      betalactams, 66% and 78%, respectively. The proportion of fluoroquinolones was 3
      5%. The average duration of the treatment periods was 10 days with the exception
      of treatment of cats with macrolide-lincosamides, where the mean period was 20
      days. Indication was mentioned only in 37% of the prescriptions.

PMID- 16108218
TI  - Reindeer warble fly larvae (Hypoderma tarandi) in a moose (Alces alces) in
      Sweden.

PMID- 16108219
TI  - [Nitric oxide suppresses permeability transition pore opening and enhances
      calcium uptake in mitochondria in vivo].
AB  - The influence of an NO donor, nitroglycerine (NG) on Ca2+ accumulation in rat
      heart and liver mitochondria was studied. A rapid dose-dependent increase in
      Ca(2+)-uptake was observed within 5 min after NG injection in vivo, with a peak
      in NG concentration of 0.5-1.0 mg/kg body weight. There is a correlation between
      a dose-dependent increase in Ca(2+)-accumulating capacity of mitochondria and
      sharp dose-dependent rise in stable NO metabolites level (NO2-, NO3- and
      nitrosothiols) and reactive oxygen species (H2O2 and hydroxyl radical, *OH) as
      well as lipid oxidation products (diene conjugates), the markers of the oxidative
      damage of the organelles in mitochondria in comparison to a whole tissue (liver)
      where only moderate increase of ROS and NO metabolites was detected. A 20-30-fold
      increase of NO3- level from 32. +/- 2.6 to 736.4 +/- 96.5 nmol/mg protein (p <
      0.05) and from 45.4 +/- 6.2 to 1395.0 +/- 121.1 nmol/mg protein (p < 0.05) in
      liver and heart mitochondria respectively also provide a strong evidence for
      nitrosative stress. The results obtained suggest that calcium elimination from
      cytosol and its increased accumulation in mitochondria (likely dependent on
      permeability transition pore blockade by NO) could account for the
      cardioprotective action of NG although resulted in the development of oxidative
      stress with following long-term alterations of the energy supply and metabolism
      of subcellular structures.

PMID- 16108220
TI  - Postconditioning prevents apoptotic necrotic and autophagic cardiomyocyte cell
      death in culture.
AB  - In the paper the data concerning the possibility of the reproduction of the
      postconditioning phenomena in the cardyomicyte culture are presented. Primary
      cultures of cardiomyocytes from neonatal rats underwent 30 minutes of anoxia
      followed by 60 minutes of reoxygenation. Three different models of
      postconditioning were used: 3 cycles of 1, 3, or 5 minutes of reoxygenation
      followed by 1, 3, or 5 minutes of anoxia, respectively. The percentage of living,
      necrotic, and apoptotic cells were determined by staining with Hoechst 33342 and
      propidium iodide. Autophagy was demonstrated by the staining of vacuolar
      structures in vivo by monodansyl cadaverine. After anoxia and reoxygenation the
      amount of living, necrotic and apoptotic cells were 79 +/- 1.5, 7.8 +/- 0.9 and
      13 +/- 1.5 %, respectively (in unstimulated cell culture 90 +/- 0.8, 3.3 +/- 0.3,
      and 5.5 +/- 0.7, P < 0.0001 for all). Postconditioning with 1 min anoxia 3-fold
      increased the amount of living cells and decreased the number of necrotic and
      apoptotic cells (P = 0.002, P = 0.02 and P = 0.043 respectively).
      Postconditioning with cycles of 3 and 5 minutes had a gradually reduced effect
      compared to cycles of 1 minute. The percentage of autophagic cells in control
      cell culture was 4.3 +/- 0.3%. This number increased after anoxia-reoxygenation
      to 14 +/- 0.8%, and was reduced by postconditioning (P < 0.001). The data
      obtained indicate that postconditioning is one of the effective methods of
      cardioprotection and could effectively decrease the amount of cardiomyocytes with
      traits of programmed or non-programmed cell death.

PMID- 16108221
TI  - [Study of mithochondrial permeability transition pore in the development of
      myocardial and vascular contractility disfunctions].
AB  - In experiments on the isolated myocardial and vascular preparations the role of
      the mithochondrial permiability transition pore (mPTP) in the development of
      reperfusion injury was investigated. Co-perfusion of the previously activated
      myocardial trabecula (MT) and arterial rings (AR) by solution collected during
      the first 5 min of isolated heart reperfusion, caused a sharp and significant
      decrease of tonic tension of both isolated preparations. Besides the significant
      inhibition of the MT and AR reactions after electrical stimulation, modulation of
      AR reaction by the influence of MT is also registered. The solution collected at
      first minutes of heart reperfusion, preserve a dilation property within 24 hours
      of storage at room temperature. Preliminary perfusion of MT and AR with methylen
      blue (MB, 10(-4) M/l) or the addition to the solution dithiothreitol (DTT, 2 x
      10(-5) M/l) and diethyl maleate (DEM, 2 x 10(-5) M/l) resulted in an almost
      complete inhibition of this dilatation influence on the isolated preparations.
      The data received testify that the solution comprise a NO-containing substance,
      possible nitrosoglutation. Pre-incubation (2 min) MT in a solution with mPTP
      activator phenylarsine oxide (PAO, 10(-5) M/l) and subsequent reperfusion with a
      control solution resulted in deep and irreversible decrease of tonic tension and
      inhibition of contractility of both isolated preparations. The received data are
      qualitatively similar to results described above. Our data and results received
      in additional experiments on isolated mitochondria allow us to assert that
      solution flowing from the ischemized heart contains the stable mitochondrial
      factor (SMF) with a significant dilatation property. An addition of MB and DEM in
      the reperfusion solution abrogated its dilation influence. Co-perfusion (10 min)
      of the injured MT and AR by the solution with nitrosoglutation (10 (-5) M/l)
      restored normal contractility of the isolated preparations and modulation of the
      AR reaction by the influence of MT. It once again confirms the presence of an NO
      containing substance in the SMF content. Thus, the mPTP activation plays the key
      role in the development ofmyocardial reperfusion injury and results in release of
      SMF, which can be the basic agent of paracrine regulation of myocardial
      contractility, coronary and peripheral vessels tone.

PMID- 16108222
TI  - [Characteristics of changes in respiratory function of humans after a long stay
      in Antarctic region].
AB  - Fifteen participants of the Antarctic expedition (men, 27-51 years old) have been
      investigated after their return from a one-year stay there. All subjects have
      signs of latent hypoxia. Compensation of hypoxic reactions depended on the
      initial state of organism oxygen regimen as well as on the features of a
      genotype. It was supposed that, after a long stay by a person in the coastal
      Antarctic conditions, the latent form of hypoxia could develop. The latter was
      accompanied by reorganizations of oxygen regimen and determined by specific
      features of a genotype.

PMID- 16108223
TI  - [Age-related characteristics of contractile vascular reactions and the content of
      oxygen free radicals and nitric oxide metabolites in BALB/c mice in conditions of
      alienation zone].
AB  - Peculiarities of changes of the endothelium-dependent and endothelium-independent
      vascular reactions of relaxation, and the content of oxygen free radicals and
      stable metabolites of nitric oxide (NO) were studied in the aorta preparations of
      BALB/c mice of the two age groups (6 and 18 months), which were born and lived in
      the Chernobyl alienation zone. The results obtained showed no endothelium
      dependent reactions of aortal smooth muscles relaxation to acetylcholine and only
      partially impaired endothelium-independent reactions to sodium nitroprusside in
      animals of both age groups. There was a significant decrease in the content of
      high-molecular nitrosothiols (HMNT) in old animals, which may signify a depletion
      of NO depot in the aorta. A decrease of HMNT levels induced an increase of the
      shares of anion nitrite and low-molecular nitrosothiols (LMNT) in the total
      amount of endogenous donors of NO in the aorta of old animals. Exposure of old
      animals to low doses of radiation resulted in an over 3-fold increase of LMNT. In
      old mice the levels of oxygen active forms, superoxide and hydroxyl radicals
      increase, while the level of H2O2 remained unchanged.

PMID- 16108224
TI  - [Inhibition of nitric oxide synthesis during bacterial shock does not prevent
      development of resistant hypotension and death in rats].
AB  - The study subject was the white rat-males Wistar after intra-peritoneal injection
      of the mixture of St. aureus and B. pyocyaneus daily cultures in the dose
      calculated as 1 milliard microbial organisms of each species per 100 g b.w., as
      well as the vascular preparations isolated from aortas of those rats. The aim is
      to study nitric oxide role in the development of resistant hypotension under
      generalization of the purulent infection. Infection of the animals with a mixture
      of gram-positive and gram-negative cultures led to the development of the
      pathological process, which can be considered as a septic (bacterial) shock. A
      primary lowering of the vascular tone caused by depression of the myocardial pump
      and contractile functions was observed. Injection of methylene blue or NOS
      blockers (L-NAME, S-methyl-thiourea) to the infected animals in the moment of
      hypotension development caused only a short-term rise in blood pressure. Survival
      rate in such animals was significantly lower compared to the control infected
      animals. Repeated injections of those agents hastened death of the experimental
      animals. The experiments in vitro revealed no dilatory effect of acetylcholine
      with preserved sensitivity of the vascular preparations to adrenomimetics and
      exogenous nitric oxide in both control infected animals and animals injected with
      methylene blue or NOS blockers. The data obtained suggested that resistant
      hypertension in terminal stages of septic shock is nitric oxide-independent.

PMID- 16108225
TI  - [Effect of oxygen and nitrogen active compounds on pH value in myometrium
      myocytes].
AB  - In suspension from a rat uterus using fluorescent pH1 probe BCECF-AM was
      established that the "apparent" pH1 value for this object was 6.72 +/- 0.02 at
      pHo = 7,4 (t = 25 degrees C, n = 5). Cell activation by 0.1 mM carbachol was
      accompanied by a rise in cytosolic pH up to 6.81 +/- 0.01. This process with
      different efficiency was inhibited by blockers of K(+)- and H(+)-channels: 0.1 mM
      4-amidopyridine, tetraethilamonium and cadmium. The blockers of passive H(+)
      transport do not inhibit completely alkalization of myoplasm that can testify in
      the favor of the non-channel way of passive transport H+ through plasmalemma. It
      was established that NO (0.1 mM sodium nitroprusside) and NO2- (10 nM)
      significantly enhanced the carbochol-induced rise of myoplasm pH in the cells
      from myometrium. It also was shown that carbachol-induced pH. in myocytes was
      increased by the addition of 10 nM H2O2. It was suggested that the studied
      compounds could influence Ca2+ transport systems by changing pH in myocytes.

PMID- 16108226
TI  - [Alterations in ATP-dependence of swelling-activated Cl- current associated with
      neuroendocrine differentiation of LNCaP human prostate cancer epithelial cells].
AB  - Increasing population of malignant, apoptosis resistant neuroendocrine (NE) cells
      due to differentiation of prostate epithelial/basal cells is a hallmark of
      advanced, androgen-independent prostate cancer, for which there is no successful
      therapy. Acquisition of apoptosis resistance involves alterations in the
      mechanisms of cell volume homeostasis, of which volume-regulate anion channels
      (VRAC) that carry swelling-activated Cl- current (I(Cl,swell)) represent one of
      the key determinants. Given that VRAC function is generally known to be ATP
      dependent, here we investigated how such dependence may evolve during NE
      differentiation of LNCaP prostate cancer epithelial cells. In the whole-cell
      patch-clamp recording mode I(Cl,swell) could be activated in response to
      hypotonicity-induced cell swelling in control and NE-differentiated (by
      incubation in membrane-permeable cAMP analogs) LNCaP cells even following total
      depletion of intracellular ATP using a cocktail of metabolic inhibitors. However,
      this basal I(Cl,swell) had about 30% higher density and was less inactivating in
      NE-differentiated cells. Inclusion of 5 mM Mg-ATP in the patch pipette caused
      I(Cl,swell) augmentation in both cell types. The augmentation in the control
      cells was more prominent and occurred mostly at the expense of a non-inactivating
      current component. We conclude that I(Cl,swell) in LNCaP cells consists of a non
      inactivating, ATP-dependent and inactivating, ATP-independent components. NE
      differentiation promotes the increase of non-inactivating component and partial
      loss of its ATP sensitivity making the whole I(Cl,swell) less ATP-sensitive as
      well. By largely avoiding the ATP metabolic control I(Cl,swell) may contribute to
      better control of cell volume under metabolic stress and thus enhance the
      survival rates of apoptosis-resistant NE cells.

PMID- 16108227
TI  - [Fatty-acidic content in the brain structures of hypothyroid rats of different
      age groups].
AB  - The content of fatty acids in the cerebral cortex and hippocampus was studied in
      an experiment on Wistar rats of the three age groups (5-weeks, puberal and old-
      20-22 weeks) with an induced hypothyroidism (simulation was achieved by a 2 week
      prior supplement of L-thyroxin and final monitoring of thyroxin levels in serum).
      It was determined that the major variations of free fatty acids were noticed in
      the cerebral cortex and hippocampus among puberal rats, and somewhat lower shifts
      in premature (5 weeks) and old animals. The increase of free fatty acids in
      premature rats was registered in spectrum C17-C22. The increase of linoleic and
      linolenic acids were registered five times higher in hippocampus. In old rats
      hyperthyroidism was characterized by more apparent shifts in fatty-acidic content
      of lipids of neocortex and less apparent in hippocampus.

PMID- 16108228
TI  - [Morphological changes of human erythrocytes during cold storage].
AB  - The work illustrates the sensitivity of microscopy method for intravital analysis
      of quantitative ratio of peripheric blood erythrocyte forms in patients with
      vibration disease when elucidating the role of morphological state of these cells
      in the formation of the pathological clinical manifestations. We have examined 61
      patients with vibration disease due to the effect of local vibration. It was
      demonstrated that vibration disease development is accompanied by a progressive
      increase of erythrocyte invaginated forms: stomatocytes in patient blood. It was
      established, that a loss of hypothermic resistance of erythrocyte form could
      serve as a diagnostic test of the pathological process manifestation degree.
      Therefore, if the accumulation rate (C, % per day) of prehemolytic erythrocyte
      forms under conditions of blood hypothermic storage (4 degrees C) is within 3.5 <
      C < 5.0 interval, the 1st stage of the disease is detected while the IInd stage
      of disease is detected when C > 5.

PMID- 16108229
TI  - [Characteristics of sciatic nerve regeneration in limb blood supply disturbance].
AB  - The submitted work is devoted to a problem of influence of the regional
      hemodynamic disturbances on nerve regeneration following its full anatomic
      breakdown and neuroraphy. In a chronic experiment on 30 white rats, an arterial
      ischemia was reproduced by ligation of the main femoral arteries: common and deep
      femoral (12 animals), while venous hypertension was reproduced by ligation of the
      main veins: common, deep femoral and big hypodermic veins (12 animals). In the
      second stage of the operation a sciatic nerve of the same limb was dissected and
      its pieces were connected by perineural seam. In the control group 6 animals were
      subjected to the operation with the subsequent imposition of the perineural seam
      on the sciatic nerve. In 7, 14, 30, 60, 90 days after operation the tissue block
      from a zone of neural anastomosis was deleted. Proximal and distal stumps of the
      operated nerve, reclaiming neuroma and hematomicrocirculating channels of the
      nerve were investigated by perfusion, histologic and electron-microscopic
      methods. It is established that the regional ischemia caused by trauma of the
      main arteries of the limb resulted in inhibition of regenerative processes in the
      operated nerve, and restoration of arterial blood circulation is essential for
      stimulation of these processes. Regional venous hypertension is not the critical
      factor for regeneration of a peripheral nerve after its anatomic breakdown and
      microsurgical neuroraphy.

PMID- 16108230
TI  - [Effect of bioactive water Naftussya with different microflora content on
      choleresis, enteroabsorbition and diuresis in rats].
AB  - Drinking of original mineral water "Naftussya" from Truskavets spa by the healthy
      adult rats during 3 weeks led to increase the urinary, biliary, cholates and
      cholesterol extraction by 54%, 72%, 69% and 83%, respectively with no influence
      on the enteric water absorption. The integral activity index was 2.55 +/- 0.21.
      Ultrafiltration of mineral water in order to eliminate microflora did not affect
      significantly tested properties (2.29 +/- 0.21) while ultra-violet irradiation of
      water increased the integral activity index to 2.67 +/- 0.47 due to enhancement
      of water absorption on 48% in the small intestine and increase of diuresis on 88%
      as well as biliary, cholesterol and cholates extraction on 74%.

PMID- 16108231
TI  - [The comparative study of the effect of new fluorine-containing guanidine
      derivate compounds and pinacidil on contractile function of the urinary bladder
      in vitro].
AB  - The effects of the new fluorine-containing guanidine-derivate compounds on
      bladder contractile functionwere examined on isolated bladder strips in vitro.
      Female rats (250-350 g) were used. The bladder was removed and placed in the room
      temperaturePSS of the following composition (mM): NaCl (118.4), KCl (4.7),CaCl2
      (2.5), MgSO4 (1.2), KH2PO4 (1.2), NaHCO3 (24.9), and D-glucose (11.1) gassed with
      O2-CO2. 95%-5%. The base of the bladder was then cut into strips 4-to 5-mm wide
      and 10-mm long. Then strips were pretensioned (0.25-0.5 g) and after 30 min of
      equilibration were contracted with an additional 60 mM KCl and again were allowed
      to equilibrate. Compounds were administered directly into the tissue bath. All
      compounds produced a concentration-dependent relaxation of isolated rat bladder
      strips.

PMID- 16108232
TI  - [Analysis of the heart rhythm variability using median spectrogram method].
AB  - The analysis of the heart rhythm variability (HRV) with the methods of median
      (built according to some realizations) and traditional spectrogram was carried
      out in groups of people with different physical conditions and with tilt test. It
      was shown that median spectrogram characterize the changes of the HRV wave
      structure more precise than the traditional one with spectrum division into three
      standard windows.

PMID- 16108233
TI  - Hypoglycemia--an enigmatic dilemma.

PMID- 16108234
TI  - Cutaneous carcinoma with mixed histology.

PMID- 16108235
TI  - Postpartum hemorrhage after cesarean delivery: an analysis of risk factors.
AB  - OBJECTIVE: To determine the incidence and risk factors for postpartum hemorrhage
      (PPH) associated with cesarean delivery. METHODS: Blood loss at cesarean delivery
      was measured and defined as 1,000 to 1,499 mL or greater than 1,500 mL and/or the
      need for a blood transfusion. Variables were identified and evaluated to
      determine the factors associated with PPH. RESULTS: There were 1,844 elective and
      2,993 nonelective cesarean deliveries over 4 years. The PPH rate in nonelective
      cesarean (6.75%) was greater than after elective cesarean (4.84%, P = 0.007).
      Risk factors for PPH after an elective operation included leiomyomata, blood
      disorders, placenta previa, antepartum bleeding, preterm birth, and general
      anesthesia. Nonelective cesarean PPH risk factors included blood disorders,
      retained placenta, antepartum transfusion, antepartum/intrapartum hemorrhage,
      placenta previa, general anesthesia, and macrosomia (odds ratio > 1.5, confidence
      interval > 1.5). CONCLUSIONS: Nonelective cesarean deliveries have a higher risk
      of PPH than women delivered electively. Risk factor identification and prevention
      should be a priority.

PMID- 16108236
TI  - Association of type 2 diabetes mellitus and seroprevalence for cytomegalovirus.
AB  - BACKGROUND: Infection is known to play a role in type 1 diabetes, but there is a
      paucity of information on its role in diabetes mellitus type 2. We examined the
      seroprevalence of selected viruses in a group of predominantly Hispanic patients
      with type 2 diabetes and control subjects without diabetes. METHODS: One hundred
      thirteen patients, 83 with type 2 diabetes and 30 control subjects, all
      undergoing hemodialysis at the same facility in San Antonio, Texas, were tested
      for antibodies against coxsackie B viruses, cytomegalovirus (CMV), and
      parvovirus. Sixty-six of these patients and 25 control subjects were tested
      bimonthly for 6 months. RESULTS: We observed a greater seroprevalence of anti-CMV
      IgG antibodies among patients with diabetes (97.6%), compared with control
      subjects (86.7%), and the difference was statistically significant [OR = 6.2, 95%
      CI: 1.1 to 36.0, P < 0.05]. Three draws on a subset of 91 patients produced still
      greater odds [OR = 12.4, 95% CI: 1.3 to 117, P < 0.05]. There were significantly
      more (P < or = 0.001) vascular complications among patients with diabetes. There
      was a colinearity of trends between diabetes, seropositivity to CMV, and age.
      CONCLUSIONS: Our findings indicated an up to 12 times greater odds of having type
      2 diabetes for persons previously exposed to CMV. Since accelerated
      atherosclerosis is also associated with diabetes and CMV, past CMV infection may
      be a common factor that links atherosclerosis and diabetes. No other viruses
      tested in this study, either coxsackie B viruses or parvovirus, showed a
      significant association with type 2 diabetes.

PMID- 16108237
TI  - Pilot study on gastric electrical stimulation on surgery-associated
      gastroparesis: long-term outcome.
AB  - OBJECTIVES: Patients with postgastric surgery gastroparesis are often
      unresponsive to conventional medical therapy. Gastric electrical stimulation
      (GES) with the use of high-frequency and low-energy neural stimulation is an
      approved technique for patients with idiopathic and diabetic gastroparesis.
      METHODS: We hypothesized that GES would improve symptoms, health resource
      utilization, and gastric emptying in six patients with postsurgical gastroparesis
      from a variety of surgical procedures. Patients were evaluated by means of the
      following criteria: symptoms, health-related quality of life, and gastric
      emptying tests at baseline over time. RESULTS: All patients noted improvements
      after device implantation for up to 46 months: the frequency score for weekly
      vomiting went from a baseline of 3.2 down to 0.4 immediately after treatment
      before settling at 1.4 by the long-term follow up. Total gastrointestinal symptom
      score went from 36.5 at baseline down to 12.3 before settling at 20.5 at long
      term follow up. Improvements were also seen in health-related quality of life and
      solid and liquid gastric emptying. CONCLUSIONS: We conclude that GES is
      associated with clinical improvements in this group of patients with either
      postsurgical or surgery-associated gastroparesis. This pilot study with long-term
      outcomes offers evidence for a new therapy for otherwise refractory patients with
      gastroparesis associated with previous surgery.

PMID- 16108238
TI  - Measurement of central venous pressure from a peripheral intravenous catheter in
      the lower extremity.
AB  - OBJECTIVES: The measurement of central venous pressure (CVP) is used to assess
      intravascular status. Although this is usually accomplished by placement of a
      central venous catheter (CVC), there are circumstances when placement of a CVC
      may be technically difficult or impossible. The current study investigates the
      feasibility of measuring CVP from a peripheral intravenous catheter. METHODS: CVP
      was simultaneously measured from a CVC and from a peripheral intravenous site.
      The continuity of the peripheral intravenous catheter with the central venous
      system was evaluated by noting the change in the pressure measured from the
      peripheral catheter during a sustained inspiratory effort and during occlusion of
      the extremity (arm or leg) above the catheter. RESULTS: The cohort for the study
      included 37 adult patients. In 8 of the 37 patients (22%), there was no increase
      in the peripheral venous pressure (PVP) in response to a Valsalva maneuver or
      occlusion of the extremity above the intravenous site. For the upper extremity
      intravenous sites without a PVP increase, the PVP-CVP difference was 11.2 +/- 6.2
      mm Hg versus 2.7 +/- 2.2 mm Hg in the patients in whom the PVP increased with
      these maneuvers (P < 0.0001). For the lower extremity intravenous sites without a
      PVP increase, the PVP-CVP difference was 7.6 +/- 4.0 mm Hg versus 2.6 +/- 1.9 mm
      Hg in the patients in whom the PVP increased (P < 0.0001). No variation in the
      accuracy of the technique was noted, depending on the size of the intravenous
      cannula, its location (upper versus lower extremity), CVP value, or patient
      positioning (supine, prone, lateral). CONCLUSIONS: Provided that the PVP
      increases to a sustained inspiratory breath and occlusion above the intravenous
      site, there is a clinically useful correlation between the PVP and the CVP.

PMID- 16108239
TI  - Diagnostic tests for rheumatic disease: clinical utility revisited.
AB  - Establishing a diagnosis of systemic rheumatic disease requires an integration of
      a patient's symptoms, physical examination findings, and the results of
      diagnostic testing. There is often a temptation by clinicians to rely heavily on
      objective measures such as the presence or absence of an autoantibody. Medical
      textbooks and the medical literature may overestimate the diagnostic utility of
      many commonly ordered tests for rheumatic disease because the tests are usually
      analyzed among patients with established rheumatic disease rather than among
      patients with an uncertain cause of symptoms as is common in practice. Few
      diagnostic tests are highly sensitive, though the antinuclear antibody in
      systemic lupus erythematosus (SLE) and the erythrocyte sedimentation rate in
      temporal arteritis are notable exceptions. Conversely, few diagnostic tests are
      highly specific; anti-proteinase-3 and antimyeloperoxidase antibodies (types of
      antineutrophilic cytoplasmic antibodies) among patients with Wegener
      granulomatosis (and related vasculitides) and anti-double-stranded and anti-Smith
      antibodies among patients with SLE may be particularly helpful in the proper
      clinical settings due to their high specificity. Anticitrullinated cyclic protein
      (anti-CCP), a newly described autoantibody that may be highly specific for
      rheumatoid arthritis, requires additional study as its utility in clinical
      practice is uncertain.

PMID- 16108240
TI  - Metabolic issues in patients with severe mental illness.
AB  - This article reviews the epidemiology of weight gain and diabetes mellitus in
      general and in patients with severe mental illness in particular. Body mass index
      is defined, and possible predictors for weight gain in patients receiving
      antipsychotic medications are also enumerated. Information on risk of association
      with type 2 diabetes mellitus is described, as well as information on
      dyslipidemias within the rubric of the metabolic syndrome. Recent consensus panel
      reports and their recommendations for ongoing patient monitoring are reviewed.
      The issue of switching antipsychotic medication in the context of a developing
      metabolic disorder is discussed with regard to appropriately balancing risk and
      benefits. Collaborative treatment between a psychiatrist and an endocrinologist
      is encouraged. The primary care physician may be required to fulfill both roles.

PMID- 16108241
TI  - Acute hepatitis E infection in a visitor to Louisiana.
AB  - A man from Africa had been visiting Mississippi and Louisiana when he had
      development of acute hepatitis. Although hepatitis E is endemic to many parts of
      the world and has been associated with large outbreaks, it has remained
      relatively uncommon in this country. With growing foreign travel and an ever
      increasing number of cases reported nationally, hepatitis E infection should be
      considered more frequently in the differential diagnosis of acute hepatitis.

PMID- 16108242
TI  - Reversible encephalopathy secondary to paratyphoid infection and concomitant
      acute Hepatitis A.
AB  - Reversible encephalopathy has been described in association with typhoid fever as
      well as nontyphoidal salmonella infections. A diagnostic dilemma as to the cause
      of encephalopathy may arise when there is coexistent acute viral hepatitis and
      suspicion of fulminant liver failure. The authors report a patient who presented
      with acute icteric hepatitis A infection and a concomitant febrile illness due to
      Salmonella paratyphi associated with progressive encephalopathy and coma. The
      young man developed high-grade fever and coma. Concomitant infection with S.
      paratyphi was diagnosed and the patient's encephalopathy resolved rapidly with
      antibiotic therapy. This is the first report of a putative association of S.
      paratyphi infection and reversible encephalopathy. Salmonella and hepatitis A
      virus infection are both transmitted via the fecal-oral route, and awareness of
      this association is important in the management of such patients.

PMID- 16108243
TI  - Hyperinsulinemic hypoglycemia precipitated by weight loss.
AB  - OBJECTIVE: To describe a case of hyperinsulinemic hypoglycemia precipitated by
      weight loss. METHODS: We present a detailed case report and results of a related
      literature search on hyperinsulinemic hypoglycemia precipitated by weight loss.
      RESULTS: The presence of an insulinoma was unveiled by voluntary weight loss and
      reduction of insulin resistance. Hypoglycemia occurred during the postprandial
      period and not at night. The diagnostic workup was accomplished without hospital
      admission. CONCLUSION: Classically, insulinomas present with weight gain and
      fasting hypoglycemia but may present with postprandial hypoglycemia and weight
      loss. Voluntary weight loss, by lowering insulin resistance, accelerates the time
      to clinical presentation of an asymptomatic insulinoma.

PMID- 16108244
TI  - Extreme hyperkalemia.
AB  - Hyperkalemia is a potentially fatal condition and is defined by a serum potassium
      level (K+) of greater than 5.5 mmol/L. The associated prevalence of cardiac
      arrhythmia increases directly with the degree of hyperkalemia. The danger in the
      majority of hyperkalemia cases is cardiac dysrhythmia, and often ventricular
      fibrillation or asystole is the terminating event. Although there are many
      previous reports addressing this threatening problem and associated therapeutic
      maneuvers, there have not been many previous reports citing the fatal
      concentration of hyperkalemia irrespective of the causes. However, it is
      uniformly accepted that a K+ concentration greater than 10.0 mmol/L is fatal
      unless urgent treatment is instituted. This report describes a case of nonfatal
      hyperkalemia of 14 mmol/L with intact survival and complete recovery. Potassium
      homeostasis is revisited, and some explanations are proffered regarding the
      protective mechanism against hyperkalemia, including transcellular flux, renal
      tubular function, and endocrine responses.

PMID- 16108245
TI  - Bisphosphonate-associated scleritis: a case report and review.
AB  - An 86-year-old female was treated for osteoporosis with alendronate, an
      aminobisphosphonate. Six weeks after alendronate therapy began, scleritis
      developed in the patient's right eye. The alendronate was discontinued, and, with
      the administration of prednisone, the symptoms of scleritis fully resolved.
      Rechallenge resulted in recurrence of the symptoms. Bisphosphonates are commonly
      used in the management of osteoporosis and are generally safe agents. Rarely,
      they have been linked with ocular inflammation. This case report reviews the
      literature on the ocular effects of bisphosphonates and discusses a possible
      mechanism for the association.

PMID- 16108246
TI  - Calciphylaxis: a rare association with alcoholic cirrhosis. Are deficiencies in
      protein C and S the cause?
AB  - Calciphylaxis is a rare condition of induced systemic hypersensitivity in which
      tissues respond to appropriate challenging agents with a sudden local
      calcification. It is characterized by acute calcium deposition in the medial
      layer of small and intermediate dermal vasculature that can lead to epidermal
      ischemia, ulceration, and necrosis. Calciphylaxis typically occurs in patients
      with end-stage renal disease who are undergoing dialysis and who have secondary
      hyperparathyroidism. Even in this population the incidence is less than 1%. The
      cause of calciphylaxis is unknown. However, it has been suggested that
      deficiencies of protein C and protein S may play a role in the pathophysiology of
      this disorder. Our patient is the fourth with cirrhosis to be reported to have
      developed calciphylaxis and adds further evidence that low levels of these
      anticoagulant factors may be an important etiologic factor for development of
      calciphylaxis. This report should alert the clinician that calciphylaxis occurs
      in patients with cirrhosis and should stimulate further research concerning the
      possible role of protein C and protein S deficiency in calciphylaxis.

PMID- 16108247
TI  - Cutaneous carcinoma with mixed histology: a potential etiology for skin cancer
      recurrence and an indication for Mohs microscopically controlled surgical
      excision.
AB  - Cutaneous carcinomas with mixed histology describe nonmelanoma skin cancers which
      have more than one histologic subtype. These include basal cell carcinomas with
      concurrent aggressive growth patterns (such as sclerosing, infiltrating,
      micronodular, keratinizing, and tumors with perineural involvement) and
      nonaggressive growth patterns (such as superficial, nodular, and follicular) and
      squamous cell carcinomas with concurrent poorly differentiated and well
      differentiated components. One mechanism of recurrence of nonmelanoma skin cancer
      may very well result from the inadequate initial treatment of cutaneous tumors
      with mixed histology. If the aggressive histologic subtype of the original tumor
      is initially not suspected based upon the pathology observed from a superficial
      biopsy specimen, the clinician may initiate therapy that would be appropriate for
      the less aggressive variant that was diagnosed. Subsequently, the more aggressive
      tumor may persist and eventually manifest as a clinical recurrence of the cancer.
      This is particularly important when there is perineural tumor involvement. We
      describe two patients whose skin cancers had more than one histologic subtype to
      demonstrate the histologic features of cutaneous malignancies with more than one
      pathologic pattern and to emphasize how inaccurate a single diagnostic biopsy can
      be. We also suggest that clinicians consider Mohs surgical excision of
      nonmelanoma skin cancers since this technique incorporates microscopically
      controlled removal of the tumor with complete pathologic evaluation of all
      surgical margins for any residual cancer.

PMID- 16108248
TI  - Herbal interaction with warfarin.

PMID- 16108249
TI  - Hypertensive disease management community outreach program in Hispanics.

PMID- 16108250
TI  - Complete resolution of fibrosing mediastinitis with corticosteroid therapy.

PMID- 16108251
TI  - Ulnar nerve deficit after catfish sting.

PMID- 16108252
TI  - [Antiparasitic drugs in pediatrics].

PMID- 16108253
TI  - [Ultrasonography and computer tomography in children].

PMID- 16108254
TI  - [Generalized reaction to BCG vaccine with fatal outcome].

PMID- 16108255
TI  - [Testicular and paratesticular tumors in infants and children].

PMID- 16108256
TI  - [Double outlet right ventricles: 19 cases].

PMID- 16108257
TI  - [Sensibility to insulin in obese children].

PMID- 16108258
TI  - [Rolandic paroxysmal epilepsy. Prognostic, electric, clinical limits. Study of 28
      cases].

PMID- 16108259
TI  - [A rare accident of parenteral nutrition by central catheter: hypertonic state
      coma].

PMID- 16108260
TI  - [Computerized axial tomography in diagnosis of multiple brain abscess].

PMID- 16108262
TI  - [A case of generalized reaction to BCG vaccine without apparent immunodeficiency
      and a fatal outcome].

PMID- 16108261
TI  - [Bronze baby syndrome and cholestatic icterus following neonatal listeriosis].

PMID- 16108263
TI  - [Autonomous thyroid nodule spontaneously cured by cystic degeneration on age
      thirteen girl].

PMID- 16108264
TI  - [A study of the effects of Bacillus strain IP 5832 on the intestinal flora of
      infants treated with antibiotics].

PMID- 16108265
TI  - [Charles-Michel Billard: a forgotten one hundred and fiftieth anniversary].

PMID- 16108266
TI  - [The treatment of neonatal hyperbilirubinemia].

PMID- 16108267
TI  - [The diagnosis and investigation of delayed puberty].

PMID- 16108268
TI  - [Statistical analysis of the variations in various biological parameters during
      phototherapy for hyperbilirubinemia in premature babies].

PMID- 16108269
TI  - [Evaluation of the results of LH-RH test in delayed puberty and hypogonadotropic
      hypogonadism].

PMID- 16108270
TI  - [Plasma androgens in boys from birth to adolescence].

PMID- 16108271
TI  - [Facial dysmorphia and arthrogryposis secondary to oligohydramnios due to
      continuous loss of amniotic fluid].

PMID- 16108272
TI  - [Changes in serum 25-hydroxyvitamin D levels in premature babies as a function of
      their environment].

PMID- 16108273
TI  - [A rapid semi-quantitative test for measuring IgM levels for the early diagnosis
      of neonatal infections].

PMID- 16108274
TI  - [Principles underlying the use of antituberculosis medication in children].

PMID- 16108275
TI  - [Epiphyseal dislocation in the new born].

PMID- 16108277
TI  - [Acute tuberculous meningitis in children. A report on 4 cases].

PMID- 16108276
TI  - [Epidemiological, clinical and evolutive aspects of haemophilus influenzae type B
      meningitis in Africa].

PMID- 16108278
TI  - [Ultrastructural studies of a secretory granulosa cell tumor of the ovary in a 12
      month old girl].

PMID- 16108279
TI  - [Chronic neurogenic hypernatremia with arhinencephaly].

PMID- 16108280
TI  - [Extensive scabies in a baby].

PMID- 16108281
TI  - [Screening of deafness at birth].

PMID- 16108282
TI  - [Bourneville's tuberose sclerosis in children].

PMID- 16108283
TI  - [Neonatal diagnosis of hypothyroidism by measurement of TSH levels: results in a
      series of 1880 cases from the University Hospital Center in Caen].

PMID- 16108284
TI  - [Cellular immunity changes in babies recovering form malnutrition].

PMID- 16108285
TI  - [Two cases of gluten intolerance presenting as dwarfism].

PMID- 16108286
TI  - [Gluten enteropathy and IgA deficiency (Crabbe-Hereman's syndrome)].

PMID- 16108287
TI  - [About 2 cases of "dry syndrome" associating xerophthalmy, xerostomy and
      cutaneous dryness].

PMID- 16108288
TI  - [A case of pulmonary hemosiderosis associated with rhumatoid arthritis with LE
      cells].

PMID- 16108289
TI  - [Hypoplasic thrombopenia with radial hypoplasia and Darler's disease].

PMID- 16108290
TI  - [Pulmonary agenesia with facial asymmetry].

PMID- 16108291
TI  - [Calcification and hernia of an intervertebral disc in a child].

PMID- 16108292
TI  - [Neonatal evidence of Cogan's syndrome].

PMID- 16108293
TI  - Translational research: moving scientific advances into the real-world setting.

PMID- 16108294
TI  - "I'm going to die of something anyway": women's perceptions of tamoxifen for
      breast cancer risk reduction.
AB  - OBJECTIVE: To investigate how ethnically diverse women who are eligible for
      tamoxifen prophylaxis because of their breast cancer risk decide about tamoxifen
      use for risk reduction. DESIGN: A qualitative intervention pilot study used focus
      groups to discuss the use of tamoxifen and to identify the concerns of ethnically
      diverse women about the preventive use of this drug. Focus group discussion
      involved exploration of the benefits and risks of tamoxifen prophylaxis,
      presentation of a standardized educational intervention, and focused discussion
      on attitudes about tamoxifen for prevention. Prominent themes emerged from
      iterative review of focus group transcripts. RESULTS: Fear of breast cancer was
      not prominent, and participants were less inclined to take tamoxifen as
      preventive therapy after receiving information. Decisions were based on
      participants' understandings of competing risks and benefits. Specifically,
      participants expressed limited willingness to take medication with potential
      serious side effects for risk reduction and were unwilling to discontinue hormone
      replacement therapy. Uneasiness about the reliability of scientific studies
      surfaced in the focus groups comprised of White and Latina women. African
      American women described faith as important to prevention. CONCLUSIONS: Women
      were wary of taking a drug for a disease they might not develop. Women felt they
      had options other than tamoxifen to reduce their risk of breast cancer, including
      early detection, diet, faith, and complementary and alternative therapies.

PMID- 16108295
TI  - A pilot church-based weight loss program for African-American adults using church
      members as health educators: a comparison of individual and group intervention.
AB  - OBJECTIVE: The purpose of this study was to examine a church-based intervention
      employing a 6-month pilot weight loss program as a strategy to improve health of
      African-American adults. DESIGN: A randomized trial design was used without a
      control group. Eligible church members were randomized into two groups: an
      intervention delivered in the group setting and an intervention delivered in the
      individual setting. SETTING: The study was conducted at an African-American
      church in Baton Rouge, Louisiana. PARTICIPANTS: Forty church members were
      enrolled in the study. Two trained church members without specialization in
      obesity treatment conducted the study. MAIN OUTCOME MEASURES: The primary outcome
      measure was weight loss. RESULTS: The program retention rate was 90%. After six
      months, a modest but significant mean weight loss was seen in all participants of
      3.3 kg. The mean weight losses in the individual and group interventions were 3.4
      kg and 3.1 kg, respectively. The mean body fat loss was 2.1 kg and 1.9 kg,
      respectively. The difference in weight loss and fat loss between the individual
      and group interventions was not statistically significant. An improvement in the
      quality of life and an increase in physical activity were reported by the program
      participants. CONCLUSIONS: A church setting may provide an effective delivery
      mechanism for a health and nutrition program. Church members may be trained to
      conduct a weight control program. Both interventions (individual and group) were
      effective in inducing weight loss.

PMID- 16108296
TI  - Perceived competence of rural South-African and rural African-American families:
      a cross-cultural assessment of structural validity.
AB  - The present study explores psychometric differences in baseline data from rural
      African-American (AA) and rural South-African (SA) adolescents to establish the
      cross-cultural validity of the Harter Perceived Competence Scale (PCSC). Two
      versions of the PCSC (one English and one Sepedi) were collected from 223 rural
      AA families and 157 rural SA families. A multinational research team was
      assembled to establish content validity of the translated versions of the PCSC.
      Principle components analysis and multiple group confirmatory factor analysis
      were used to investigate structural validity. The results have implications for
      intercontinental research and the theoretical construct of perceived competence.

PMID- 16108297
TI  - Empowering factors for regular mammography screening in under-served populations:
      pilot survey results in Tennessee.
AB  - BACKGROUND: Mammography screening can reduce breast cancer burden, however it
      continues to be underutilized by low-income women even though their health
      insurance provides free mammograms. While a vast majority of eligible women in
      Tennessee do not receive the free mammograms available to them, 25% of women with
      comparable backgrounds do. OBJECTIVE: To describe the influences that may have
      led these women to adhere to mammography screening guidelines in order to develop
      a case-control study for further research. DESIGN: Healthcare workers conducted
      personal interviews on mammography knowledge, attitudes, and behaviors. SETTING:
      In-home. PARTICIPANTS: All were members of the Managed Care Organization Access
      MedPlus with incomes <200% above poverty. All were adherent to mammography
      guidelines per medical records. Fifty-eight respondents were Black, 27 were
      White, and all were at least 40 years old. RESULTS: Participants recognized
      breast cancer risk factors, warning signs, and the importance of early detection
      to survival. 75% reported a family history of any cancer type, 77% knew someone
      who had breast cancer, and 52% knew someone who had died from it. These women
      expressed that screening strongly reassured them. Willing to work with their
      doctors, they trust the health system's ability to treat breast cancer and are
      generally satisfied with their health care. CONCLUSIONS: Repeat regular
      mammography screening is positively associated with higher knowledge about risk
      factors, warning signs, screening, and treatment. Trust in the healthcare system,
      ability to work with physicians, and support by family and friends lead low
      income, adhering women to be proactive in seeking mammography screenings.

PMID- 16108298
TI  - Recruitment strategies for minority participation: challenges and cost lessons
      from the POWER interview.
AB  - BACKGROUND: The importance of recruiting and retaining women from diverse
      populations is well recognized; however, the recruitment process often presents
      greater challenges at higher costs than initially anticipated. OBJECTIVES: To
      describe recruitment strategies and costs from a study evaluating women's
      preferences regarding tamoxifen use for primary prevention of breast cancer.
      DESIGN: Description and analysis of recruitment strategies, outcomes, and costs
      for a cross-sectional interview study. SETTING: University hospital and community
      sites. PARTICIPANTS: 932 racially and ethnically diverse women respondents, of
      whom 771 completed the screening process (aged 27-87). INTERVENTION: Women were
      recruited and screened by using the Breast Cancer Risk Assessment Program (BCRA
      version 1, National Cancer Institute). Eligibility required an estimated five
      year breast cancer risk of at least 1.7%. Recruitment goals targeted a high
      percentage of ethnic minorities. METHODS: Recruitment strategies included direct
      mail, flyers, newspapers, media advertising, and community outreach. RESULTS: Of
      the 771 screened women, 341 (44%) met eligibility criteria and 255 (33%)
      completed interviews (76.9% White, 10.6% Latina, 7.0% Asian, 3.9% African
      American, 1.6% Native American). Recruitment costs averaged US $113/screened
      participant. Direct mail and community contact yielded the largest number of
      participants (312 screened, 205 eligible). Radio advertising provided few
      participants (one screened, one eligible) at high cost. CONCLUSIONS: Recruiting
      an ethnically diverse sample presented multiple challenges. We recommend that
      future studies budget adequately for recruitment time and costs, develop ongoing
      relationships with key community leaders, evaluate recruitment strategies
      closely, and report detailed recruitment findings to the research community.

PMID- 16108299
TI  - Activity of 11beta-hydroxysteroid dehydrogenase type 2 in normotensive blacks and
      whites.
AB  - BACKGROUND: Salt-sensitive hypertension occurs more commonly in Blacks than in
      Whites. A decrease in activity of the enzyme 11betaHSD2 that results in
      overstimulation of the mineralocorticoid receptor by cortisol could contribute to
      greater retention of sodium in Blacks. We tested the hypothesis that less
      activity of the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) is
      present in Blacks than in Whites. METHODS: Eighty-nine subjects (42 Whites and 47
      Blacks), ages 12 to 24 years were recruited from a young cohort that was followed
      longitudinally in a study of blood pressure regulation. For purposes of study,
      they were admitted to the General Clinical Research Center. Excretion of
      tetrahydrocortisol (THF), 5alpha-THF, and tetrahydrocortisone (THE) was measured
      in 12-hour overnight urine collections. In vivo 11betaHSD2 activity was estimated
      from the urinary (THF + 5alpha-THF)/THE) ratio. RESULTS: Blacks appeared to
      retain more sodium as evidenced by a lower level of 2-hour upright plasma
      aldosterone (P<.001) and marginally lower plasma renin activity (P=.06). The (THF
      + 5alpha-THF)/THE ratio in Blacks and Whites was similar: 0.91 +/- 0.41 (standard
      deviation), 0.86 +/- 0.52, 1.13 +/- 0.36, and 0.66 +/- 0.26, in White males,
      White females, Black males, and Black females, respectively; P=.35 for an overall
      effect of race. CONDUSION: 11betaHSD2 activity appears to be similar in Blacks
      and Whites and probably contributes minimally, if at all, to race differences in
      sodium retention.

PMID- 16108300
TI  - Acculturation and cardiovascular disease screening practices among Mexican
      Americans living in Chicago.
AB  - OBJECTIVE: To examine acculturation as a correlate of cardiovascular disease
      screening practices among Mexican Americans. METHODS: A modified Behavioral Risk
      Factor Surveillance System (BRFSS) survey was administered to adults age 18 and
      older in four Chicago neighborhoods during the winter of 2000 (N=435). RESULTS:
      Regression analyses that accounted for complex sampling design found that Mexican
      Americans who were acculturated, were female, and had healthcare coverage were
      more likely to have been screened after controlling for age, healthcare coverage,
      education, and marital status. Acculturated Mexican Americans were 4.97 times
      more likely to have had blood cholesterol screening, 3.4 times more likely to
      have had blood pressure screening, and 7.99 times more likely to have had a
      routine checkup in the preceding two years when compared to unacculturated
      Mexican Americans. Mexican Americans with healthcare coverage were more likely to
      have had their blood pressure checked and to have obtained a routine check-up
      than did those without coverage. Women were more likely to have had a blood
      pressure screening and have obtained a routine check-up in the past two years.
      CONCLUSIONS: The results suggest that more acculturated Mexican Americans, as
      well as those who are female and who have healthcare coverage, are more likely to
      obtain cardiovascular disease (CVD)-related screenings. The findings indicate a
      need for promoting CVD-related screenings among Mexican Americans and underscores
      the need for Spanish-speaking health professionals.

PMID- 16108301
TI  - The global burden of chronic kidney disease and the way forward.
AB  - BACKGROUND: Chronic kidney disease (CKD) is increasing worldwide at an annual
      growth rate of 8%. Regional differences exist in the epidemiology of the
      condition, and non-Whites are more affected. METHODS: An English-language
      literature search using Medline (January 1984-October 2003) was done to assess
      research/review articles on burden and prevention of CKD. Particular attention
      was paid to epidemiology and prevention of chronic kidney diseases. RESULTS: The
      prevalence of CKD is higher in developing countries than in the developed world.
      The most common causes of CKD in the developing countries are chronic
      glomerulonephritis and systemic hypertension, diabetic nephropathy being the most
      common cause in Europe, the United States, and Japan. Factors contributing to the
      regional differences in the etiology and prevalence of CKD are race and
      ethnicity, genetic predisposition, increasing prevalence of type 2 diabetes,
      mortality caused by other disease, obesity, and possibly cigarette smoking. The
      control of hypertension, dyslipidemia, proteinuria, obesity, avoidance of low
      birth weight, smoking, and preventing ingesting of heavy metals such as lead are
      intervention strategies that retard or prevent progression of renal diseases. The
      magnitude of the existing burden of illness caused by renal failure, the
      projections for increasing incidence of CKD, and the limitations of our existing
      treatments for renal insufficiency all point to the need for clinical and
      population-based interventions aimed at prevention of CKD. CONCLUSIONS: A
      comprehensive health education campaign and screening of the general populace are
      needed in order to detect chronic kidney disease early. These measures will
      ensure appropriate and timely institution of proven measures to halt or reduce
      progression of CKD.

PMID- 16108302
TI  - A family history of diabetes is related to abnormal insulin sensitivity in
      African-Caribbean girls of low birth weight: is catch-up weight important?
AB  - This retrospective cohort study examined the relationship of birth weight, family
      history of diabetes (FamHx), and current weight to insulin resistance in Black
      girls and boys on the Caribbean island of Barbados. A cohort of 56 low birth
      weight (LBW) and 120 normal birth weight (NBW) adolescents born between January
      1, 1986, and December 31, 1988, were recruited for study participation in 2002.
      FamHx was ascertained by questionnaire. Body mass index (BMI) and waist
      circumference (WC) were used to assess fat distribution. Fasting blood glucose
      and insulin were measured from blood samples drawn from each adolescent
      participant. Insulin resistance was estimated by the homeostasis model assessment
      (HOMA) technique. These data show that only among LBW girls was a positive (+)
      FamHx associated with higher HOMA (FamHx "Yes"=1.22 +/- 0.298 vs "No"=0.811 +/-
      0.452; P=.032). No significant relationships were observed among boys. Further
      analyses revealed that compared to their NBW counterparts, LBW girls without
      FamHx, had a smaller WC (69.70 +/- 9.88cm vs 76.70 +/- 15.64cm, respectively;
      P=.055). In contrast, LBW girls with a (+) FamHx had similar mean WC (77.71 +/-
      16.46cm) to those of NBW girls with (+) FamHx (WC=71.50 +/- 10.38cm; P=.405).
      These data indicate that along with a family history of diabetes, catch-up weight
      may be important in assessing diabetes risk in Black Caribbean LBW adolescent
      girls.

PMID- 16108303
TI  - Distribution and determinants of coronary artery disease in an urban Pakistani
      setting.
AB  - OBJECTIVE: We assessed the distribution of coronary artery disease (CAD) and its
      association with the major biological risk factors and behaviors among Pakistanis
      presenting at a tertiary care hospital in Karachi, Pakistan. METHOD: An
      epidemiologic cross-sectional study was conducted at the Aga Khan University
      Hospital (a teaching hospital) in Karachi, Pakistan. A total of 600 adult (> or
      =18 years of age) patients visiting family practice clinics for general check-up
      were included. The association of biological risk factors with CAD (smoking,
      obesity [body mass index (BMI)], hypertension, family history of ischemic heart
      diseases [IHD], sedentary lifestyle, diabetes mellitus, total cholesterol, low
      density lipoprotein [LDL] levels, high density lipoprotein [HDL] levels, and
      triglycerides) were assessed. RESULTS: On univariate analysis, age > or =40
      years, early menopause, BMI > or =29.9 kg/m2, diabetes, high cholesterol, and
      positive family history of IHD were independently associated with CAD. We found
      age > or =40 years, diabetes, and positive family history of IHD strongly related
      with CAD on multivariate analysis. CONCLUSION: Looking at the strong association
      of major risk factors with CAD, the unique characteristics of Pakistanis must be
      studied in depth, with focus on high-risk groups.

PMID- 16108304
TI  - Familial roles of older African-American women with type 2 diabetes: testing of a
      new multiple caregiving measure.
AB  - OBJECTIVE: This study describes the development and validation of a new multiple
      caregiving (MC) measure and examines how familial caregiving relates to family
      composition and psychosocial factors among older African-American women with type
      2 diabetes. RESEARCH DESIGN AND METHODS: The study sample included 345 African
      American women with type 2 diabetes who participated in two lifestyle behavior
      interventions. A new 12-item survey of caregiving perceptions was tested for
      internal reliability and construct validity of two empirically defined scales (MC
      role and MC-barriers). Multiple caregiving (MC) constructs were validated by
      using baseline measures of diabetes quality of life, social support, stress,
      diabetes competence, and self-care barriers. Correlational, analysis of variance,
      and multivariate analyses were used to examine the associations among familial MC
      variables and psychosocial and household factors. RESULTS: Surveys were completed
      by 299 (87%) participants who were an average of 60 years of age, with 10 years
      of diagnosed diabetes and 11 years of education. Both MC-role and MC-barriers
      scores were positively associated with putting the family's needs first,
      difficulty saying "no" to family, and the number of adults living in the
      household. MC-barriers were associated negatively with quality of life, and
      positively with stress, barriers to diabetes self-care, and negative perceptions
      of diabetes competence. In a multivariate model, age and difficulty saying "no"
      to family seeking help were significant independent predictors of MC-barriers.
      CONCLUSIONS: Findings suggest that a better understanding of African-American
      women with diabetes in the context of family and caregiving roles may be
      important to identifying culturally meaningful strategies to improve self-care
      behaviors.

PMID- 16108305
TI  - Health belief model factors in mammography screening: testing for interactions
      among subpopulations of Caribbean women.
AB  - OBJECTIVES: To explore the implementation of health belief models in breast
      cancer screening and elucidate its potential to offer avenues for intervention
      among variables that may be easily amenable to change. DESIGN: The relations
      between three major cognitive factors-cancer knowledge, perceived personal risk,
      and beliefs about treatment efficacy-and mammography utilization were examined by
      using analysis of variance (ANOVA) and regression analyses. PARTICIPANTS: A large
      sample of women (N=1364) between 50 and 70 years of age. The women were of six
      ethnicities: US-born European Americans, US-born African Americans, Dominicans,
      Haitians, English-speaking Caribbeans, and Eastern Europeans. RESULTS: All three
      variables were significantly associated with screening behavior in zero-order
      correlations. However, only perceived risk and treatment efficacy remained
      significant in multiple regressions controlling for background variables. Perhaps
      most importantly, while there were mean-level differences in the cognitive
      variables across the six groups, only one of the 15 interaction terms was
      significant, attesting to the generalizable effect of these health belief
      variables upon screening behavior in understudied groups of minority women.
      CONCLUSIONS: The results are discussed in the context of health belief models and
      implications for interventions tailored to the health belief profiles
      characterizing women from each group are presented.

PMID- 16108306
TI  - Ethnicity and breast cancer in Hawaii: increased survival but continued
      disparity.
AB  - OBJECTIVES: To examine ethnic variation in survival among 7722 women diagnosed
      with invasive breast cancer in Hawaii between 1990 and 2002 and to extend
      previous multivariate analyses by adding a new prognostic variable: estrogen
      receptor/progesterone receptor (ER/PR) status. DESIGN: Cox regression analysis of
      retrospective data. SETTING: Population-based data from the Hawaii Tumor
      Registry, which is part of the National Cancer Institute's Surveillance,
      Epidemiology, and End Results Program. PARTICIPANTS: 7722 women in 5 ethnic
      groups--Caucasian, Chinese, Japanese, Filipino, and Native Hawaiian--diagnosed
      with invasive breast cancer between 1990 and 2002. MAIN OUTCOME MEASURE:
      Survival, examining death from breast cancer and death from a cause other than
      breast cancer. RESULTS: Compared to Caucasians, significantly smaller proportions
      of Japanese and Chinese women and larger proportions of Native Hawaiian and
      Filipino women were diagnosed in later stages of disease and at earlier ages. The
      four minority ethnic groups had higher rates of ER+PR+ tumors than Caucasians.
      For both causes of death, ethnic disparities in survival were reduced, but still
      existed, after controlling for age, stage, and ER/PR status. Japanese had the
      highest rates of survival for either cause of death. Native Hawaiians and
      Filipinos had the lowest rates of survival for breast cancer, and Native
      Hawaiians and Caucasians had the lowest rates of survival for other causes of
      death. CONCLUSIONS: Future studies should examine other reasons for continued
      ethnic differences in breast cancer survival in Hawaii, including socioeconomic
      status, access to insurance, adequacy of recommended screening frequency,
      comorbid conditions, treatment appropriateness and compliance, and genetic
      markers of tumor aggressiveness.

PMID- 16108307
TI  - Ethnic variation in health-related quality of life among low-income men with
      prostate cancer.
AB  - OBJECTIVE: To describe and compare health-related quality of life (HRQOL) among
      Hispanic, African-American, and Caucasian men with localized prostate cancer.
      DESIGN: Observational study of low-income, ethnically diverse men with non
      metastatic prostate cancer. SETTING: Statewide public assistance program in
      California. PARTICIPANTS: 208 men (51 Caucasian, 115 Hispanic, and 42 African
      American men) with non-metastatic disease. INTERVENTIONS: Radical retropubic
      prostatectomy, radiation therapy, and hormonal therapy. MAIN OUTCOME MEASURES:
      Validated instruments measured general and disease-specific HRQOL, anxiety and
      fear of recurrence, spirituality, symptom distress, and self-efficacy. RESULTS:
      Hispanic men with prostate cancer were less educated, more often in significant
      relationships, and had more variable incomes compared with men of other
      ethnic/racial backgrounds. In univariate analyses, Caucasian men reported better
      physical function but less spirituality, while Hispanic men reported worse sexual
      function. Multivariate analysis revealed that Hispanic men had significantly
      worse physical function, bowel function, and bowel bother. African-American men
      experienced greater anxiety over recurrence. African-American and Hispanic men
      were more spiritual than Caucasian men. CONCLUSIONS: Greater attention to
      demographic variations in HRQOL may allow physicians to improve outcomes across
      ethnicities in low-income men with prostate cancer by offering more specialized
      counseling and providing referral to social support systems.

PMID- 16108308
TI  - Religion, sociodemographic and personal characteristics, and self-reported health
      in whites, blacks, and Hispanics living in low-socioeconomic status
      neighborhoods.
AB  - OBJECTIVE: This study examines the multifaceted role of race/ethnicity in the
      relationship between religiosity and health. METHODS: Analysis of variance
      (ANOVA) and pairwise comparisons were used to compare the means for health,
      religiosity, and personal characteristics in Blacks, Whites, and Hispanics. A
      simultaneous-equation model with five equations modeled the relationship between
      physical health, mental health, self-rated health, organizational religiosity,
      and non-organizational religiosity. Qualitative data were used to help interpret
      quantitative results. RESULTS: Health outcomes, religiosity, reasons cited for
      being a member of a religious organization, and personal factors differed by
      race/ethnicity. Overall, individuals with more social resources tend to have
      higher organizational religiosity and better health, while individuals with fewer
      social resources tend to have higher non-organizational religiosity and poorer
      health. The model indicates the complexity of the relationships between
      race/ethnicity, religiosity, and health. Blacks reported higher organizational
      and non-organizational religiosity than Whites, while Hispanics reported higher
      non-organizational religiosity, after controlling for sociodemographic and
      personal factors and reasons cited for belonging to a religious organization.
      Being Black was directly associated with lower mental health and self-rated
      health; however, being Black was indirectly positively associated with mental
      health through organized religiosity and indirectly negatively associated with
      physical and mental health through non-organizational religiosity. Being Hispanic
      was directly associated with worse self-rated health but was indirectly
      positively associated with mental health through organizational religiosity.
      CONCLUSION: The role of race/ethnicity in the relationship between religiosity
      and health is complex, but the findings presented in this paper offer insights
      into the nature of these associations.

PMID- 16108309
TI  - Ethnicity as manifest in drug-specific vocabulary and subsequent risk of starting
      cannabis use in early adolescence.
AB  - Working knowledge or vocabulary of drug slang, as a manifestation of learned
      behavior, might help predict or explain risk of starting to use cannabis in early
      adolescence. To study this issue, an epidemiologic sample of 1,255 11- to 12-year
      olds was assessed for knowledge of cannabis slang terms in 1992, with follow-up
      in 1993 and 1994. The basic design is that of a prospective and longitudinal
      study, with recruitment of an epidemiologic sample of children as they entered
      primary school in a single metropolitan area, also with baseline assessments and
      randomization to intervention conditions, and subsequent multiple waves of follow
      up assessment. Youths assessed in 1992 and who were familiar with terms such as
      blunts, Mary Jane, roach, and herb were more likely to start using cannabis
      within the subsequent two years of the follow-up interval, as compared to other
      youths (estimated relative risk, RR=11.0; 95% CI 3.6-33.7; P<.001). A youth's
      working vocabulary may signal important variations in health- and disease-related
      behavior, such as illegal drug use.

PMID- 16108310
TI  - Disparities in maternal outcomes among four ethnic populations.
AB  - OBJECTIVE: To examine racial disparities in adverse maternal outcomes among four
      ethnic groups in the United States. DESIGN, SETTING, AND PARTICIPANTS: A total of
      1,030,350 women aged 13 to 55 who delivered in 1998 and 1999. Data were
      abstracted from the National Inpatient Sample. MAIN OUTCOME MEASURES: Race was
      categorized as White, African-American, Hispanic, and Asian/Pacific Islander.
      Maternal outcome measures included preterm labor, hypertensive disorders of
      pregnancy, gestational diabetes, antepartum hemorrhage, membrane disorders,
      cesarean section, and postpartum hemorrhage. RESULTS: African Americans were more
      likely to have preterm labor (odds ratio [OR] 1.71), preeclampsia (OR 1.59),
      transient hypertension of pregnancy (THP) (OR 1.13), pregnancy-induced
      hypertension (PIH) (OR 1.38), diabetes (OR 1.26), placenta previa (OR 1.78),
      placental abruption (OR 1.52), premature rupture of membranes (PRM) (OR 1.19),
      infection of the amniotic cavity (IAC) (OR 1.95), and cesarean section (risk
      ratio [RR] 1.08); Hispanics were more likely to have diabetes (OR 1.44), placenta
      previa (OR 1.20), IAC (OR 1.15), and cesarean section (RR 1.06); and
      Asian/Pacific Islanders were more likely to have diabetes (OR 2.05), placenta
      previa (OR 1.57), PRM (OR 1.26), IAC (1.79), and postpartum hemorrhage (OR 1.19).
      CONCLUSIONS: African Americans had the worst outcomes when adjusted for
      sociodemographic characteristics and comorbidities. Infection, gestational
      diabetes, and control of hypertension, especially among African Americans, are
      the most significant preventable risk factors contributing to disparities. By
      increasing access to health services, health education, and appropriate perinatal
      care in minority populations, improvements are likely to occur across multiple
      measures including frequencies of preterm labor, cesarean section, and
      gestational diabetes.

PMID- 16108311
TI  - Preventive care in the United States: are blacks finally catching up?
AB  - OBJECTIVE: To evaluate rates of preventive care among Blacks in specific
      demographic categories, such as age, income, gender, and Caribbean descent.
      DESIGN, SETTING, AND PARTICIPANTS: Data from the Commonwealth Fund 2001 Health
      Care Quality Survey, conducted from April through November 2001, which involved
      telephone interviews with a nationally representative sample of 6,722 adults age
      18 and older living in the continental United States. Analysis focuses on the
      subset of Black respondents in comparison to Whites and Hispanics (n=5678). MAIN
      OUTCOME MEASURES: Rates of preventive care including primary care visits,
      cholesterol and blood pressure screening, diabetes care, and cancer screening.
      RESULTS: Blacks have rates of preventive care comparable to those of Whites, with
      higher rates for some services. Overall, Blacks did better than Hispanics for
      most of the preventive measures studied. An evaluation of specific demographic
      subgroups of Blacks shows that certain populations, such as men and the
      uninsured, have lower rates of some preventive care measures. For example, Black
      men are less likely to report having a physical exam than Black women (odds ratio
      [OR] 0.53, 95% confidence interval [CI] 0.37-0.77) as well as less likely to
      report blood pressure screening in the prior year (OR 0.58, 95% CI 0.34-0.98).
      CONCLUSIONS: While high levels of mortality persist, Blacks fare relatively well
      in terms of selected preventive care services. Although focus on prevention is
      still a key concern, evaluating other causes of increased mortality, including
      differences in follow-up, referral, and quality of care, is also important.

PMID- 16108312
TI  - Why does adult African-American smoking prevalence in California remain higher
      than for non-Hispanic whites?
AB  - OBJECTIVES: To explain why, contrary to national trends, adult California African
      American (AA) smoking prevalence remains higher than for non-Hispanic Whites (W)
      and to explore how future rates might change. METHODS: Data from the random-digit
      dialed California Tobacco Surveys from 1990 to 2002 (N=16,000-21,000) allowed for
      the examination of differences in current smoking prevalence, ever smoking
      (uptake), and successful smoking cessation over time by race/ethnicity and age
      group. RESULTS: African-American (AA) adolescent (12-17 years) smoking prevalence
      was lower than Ws through 1996, but similar thereafter because of marked declines
      for Ws. After 1990, AA young adult (18-29 years) smoking prevalence was
      consistently 25% lower than Ws', and no evidence of delayed AA smoking initiation
      was seen. However, among older age groups (30-44 years and 45+ years), AA smoking
      prevalence was much higher, yielding higher overall adult (18+ years) prevalence.
      While ever smoking (uptake) was generally lower among AAs, successful cessation
      (5+ years) was much lower among AA adults, especially older age groups.
      CONCLUSIONS: Continued higher adult California AA smoking prevalence results from
      less successful quitting in older age groups. Increased successful cessation is
      critical for reducing near-term prevalence. Long-term forecasting is difficult
      because both AA and W adolescents now smoke at comparably low rates.

PMID- 16108313
TI  - For the patient. Screening for breast cancer: it's not that black and white.

PMID- 16108314
TI  - For the patient. Regular mammography screening: making it matter.

PMID- 16108315
TI  - For the patient. Is better care meaning better health for blacks?

PMID- 16108316
TI  - [The significance of the interaural latency difference of VEMP].
AB  - OBJECTIVE: To investigate the significance of the interaural latency (IAL)
      difference of the latency of VEMP and to raise the sensitivity of the test.
      METHOD: Vestibular evoked myogenic potentials (VEMP) were tested in 20 healthy
      subjects; 13 patients with acoustic neuromaor cerebellopontile angle occupying
      lesions and 1 patient with multiple sclerosis. IAL differences of the wave
      p13,n23 and p13-n23 (abbreviatd as /delta p13/, /delta n23/ and /delta p13-n23/,
      respectively) were analysed to determine the normal range and the upper limit of
      the norm data. Four illustrative cases with the abnormality of the IAL difference
      were given as examples. RESULT: The upper limit of the IAL of /delta p13/ was
      1.13 ms; that of the /delta n23/ was 1.38 ms and that of /delta p13-n23/ was 1.54
      ms. The /p13-n23/ latency between the right and left side had no significant
      difference (P > 0.05). CONCLUSION: /delta p13/, /delta n23/ and /delta p13-n23/,
      especially /delta p13/ of VEMP can suggest abnormality in the neural pathway and
      it may be applicable in practice.

PMID- 16108317
TI  - [Korner's septum and congenital aural atresia].
AB  - OBJECTIVE: To discuss the anatomic characters and clinical importance of aural
      atresia coexisted with Korner's septum. METHOD: Fifty patients with aural atresia
      coexisted with Korner's septum were analyzed retrospectively, in which the
      reconstruction surgery was performed, and high resolution temporal bone CT scan
      in the coronal and axial plane were taken preoperatively. RESULT: Among 50
      patients, 39 had well-developed Korner's septum. The others (11/50) had
      incomplete Korner's septum, which were porotic continued with antrums, under
      powerful microscopic inspection. The ossicular reconstruction was performed
      successfully in 41 patients, while that of the other 9 had to suspend because of
      displacement such as low tegmen and backward processus condylaris of mandible.
      CONCLUSION: The high resolution temporal bone CT is indispensable to the
      operation of aural atresia coexisted with Korner's septum.

PMID- 16108318
TI  - [Tympanoplasty and mastoidectomy in patients with large perforation of tympanic
      membrane in pars tensa].
AB  - OBJECTIVE: To present the experiences of tympanoplasty in patients with large
      perforation of tympanic membrane in pars tensa. METHOD: Of 147 patients who
      underwent surgery for chronic otitis media with large perforation of tympanic
      membrane in pars tensa,101 patients without mastoid problem underwent
      tympanoplasty, 46 patients who had evidence of middle ear, antral/epitympanic, or
      mastoid disease underwent tympanoplasty with mastoidectomy. RESULT: The tympanic
      membrane graft take rate for the entire group of 147 patients was 96.6% (142
      grafts succeed). The average postoperative pure tone air-bone gap was (16.6 +/-
      10.9) dBHL after 3 months of the operation. CONCLUSION: To patients with chronic
      supperative otitis media and large perforation of tympanic membrane, the CT scan
      before operation and detailed exploration of tympanum are necessary. The drainage
      of Eustachian tube, attic and antrum must be enough. The cartilage-perichondrium
      composite is an ideal material for reconstruction of the drum, the attic and the
      posterior tympanum.

PMID- 16108319
TI  - [The development of auditory capability for infants after cochlear implantation].
AB  - OBJECTIVE: The purpose of this study is to analyze the auditory capability of
      infants before and after cochlear implantation by using IT-MAIS questionnaire.
      METHOD: Eighty-six prelingually deaf patients participated in this study. They
      received a cochlear implant at the age of 1 to 3 yr. The audiologists who were
      trained for the research used the IT-MAIS questionnaire. Audiologists asked for
      the parents' answers face to face and recorded all the information about the
      patient's spontaneous auditory behavioural responses including vocalization,
      behaviour, spontaneous alerting to sound and deriving meaning from sound. The
      evaluation was performed before operation and 1 month, 3 months, 6 months, 1 year
      after switch-on. RESULT: The scores of question 1 were significantly different
      between pre-operation and 1, 3, 6, 12 months after switch-on (P = 0.000, 0.000,
      0.000, 0.000). The scores of question 2 were significantly different between pre
      operation and 6, 12 months after switch-on (P = 0.000, 0.000). The scores of
      question 3 were significantly different between pre-operation and 3, 6, 12 months
      after switch-on (P = 0.001, 0.000, 0.000). The scores of question 4 were
      significantly different between pre-operation and 3, 6, 12 months after switch-on
      (P = 0.002, 0.000, 0.000). The scores of question 5 were significantly different
      between pre-operation and 1, 3, 6, 12 months after switch-on (P = 0.046, 0.00,
      0.000, 0.000, 0.000). The scores of question 6 were significantly different
      between pre-operation and 3, 6, 12 months after switch-on (P = 0.037, 0.000,
      0.000). The scores of question 7 were significantly different between pre
      operation and 3, 6, 12 months after switch-on ( P = 0.000, 0.000, 0.000). The
      scores of question 8 were significantly different between pre-operation and 6, 12
      months after switch-on (P = 0.001, 0.001). The scores of question 9 were
      significantly different between pre-operation and 3, 6, 12 months after switch-on
      ( P = 0.023, 0.000, 0.000). The scores of question 10 were significantly
      different between pre-operation and 12 months after switch-on (P = 0.048).
      CONCLUSION: Most of the patients showed no consistent response to sound in
      everyday life before implantation. After cochlear implantation, a significant
      increase in auditory capability occurred. The children demonstrated faster
      development of vocalization behaviour and spontaneous alerting to sound than
      deriving meaning from sound.

PMID- 16108320
TI  - [Remov ing the tumor of the cerebellopontile angle with microsurgery to treat the
      secondary trigeminal neuralgia].
AB  - OBJECTIVE: In order to explore the relationship between the tumor of
      cerebellopontile angle(CPA) and trigeminal neuralgia and to select the surgical
      treatment. METHOD: With retrosigmoidal approach, the tumors of CPA were removed
      in 56 patients with the tumor of CPA and coexisting trigeminal neuralgia. The
      trigeminal nerves were decompressed with microsurgery. RESULT: All tumors were
      totally removed except one meningcoma which was removed by only 2/3 parts. Post
      operatively, trigeninal neuralgia disappeared with no cases of severe
      complications or death. CONCLUSION: The pressure to the root of trigeminal nerve
      which comes from the tumor of CPA may be one of the etiologies of trigeminal
      neuralgia, which could be treated with the removal of the tumor of CPA. The
      micrurgy of removing the tumor with retrosigmoidal approach is an ideal
      functional operation. The application of endoscope could increase the rate of
      total removement and reduce the complications.

PMID- 16108321
TI  - [Relationship between fibrinogen content and the protracted inflammation of
      secretory otitis media].
AB  - OBJECTIVE: To study the relationship between fibrinogen content and the
      protracted inflammation of secretory otitis media(SOM). METHOD: The fibrinogen
      content of 98 patients with SOM was monitored with von-clauss technique at
      different stages. RESULT: Sixty-two patients of 98 patients with SOM experiences
      were not cured after the treatment by myringopuncture. The positive rate and the
      concentration of fibrinogen in the protracted group were 72.58% and (0.568 +/-
      0.206) g/L respectively, higher than those in the cured group, 30. 56% and (0.350
      +/- 0.124) g/L ( P < 0.05 in all ); fifty-two of sixty-two patients in protracted
      group were not cured after the second treatment of myringopuncture, the
      concentration of fibrinogen in the second protracted group were (1.241 +/- 0.146)
      g/L, higher than that in the first protracted group,(0.685 +/- 0.251) g/L (P <
      0.01). CONCLUSION: Fibrinogen content has significant relationship with the
      protracted inflammation of SOM. It might play an important role in the
      pathological course of middle ear adhesions.

PMID- 16108322
TI  - [Research on the high-frequency domain of transiently evoked otoacoustic
      emissions].
AB  - OBJECTIVE: To evaluate the clinical use of transiently evoked otoacoustic
      emissions (TEOAE) in patients with high-frequency sensorineural hearing loss,
      comparing the result of TEOAE with audiometry to find the correlation between
      them. METHOD: Fourteen normal adults and 25 patients with high-frequency hearing
      loss were measured with TEOAE25 analyzer system and OB822 audiometer
      respectively, to compare the changing trend of the two examinations. RESULT: In
      the domain of 1.5 to approximately 4.5 kHz, there was significant difference of
      TEOAE between normal cases and hearing-loss cases. The results of TEOAE and
      audiometry had correlation with each other. The changing trend of the two
      examinations was accordant. CONCLUSION: Combined with pure tone audiometry, TEOAE
      could discover the degree and range of high-frequency hearing loss more
      correctly.

PMID- 16108323
TI  - [The effect of high-rate electrical stimulation on excitability of auditory nerve
      in Guinea pigs].
AB  - OBJECTIVE: To assess the effect of high-rate electrical stimulation on
      excitability of the auditory nerve by recording the change of amplitude of the
      electrically evoked auditory brainstem responses (EABR). METHOD: After guinea
      pigs were in the anesthetic state, both bullae were exposed and the round window
      membranes incised. A standard electrode array was carefully inserted a distance
      of approximately 4 mm into the scala tympani of the both experimental cochlea and
      the control cochlea. The most apical electrodes were used as stimulating
      electrodes. The round window was then sealed with crushed temporal muscle. The
      electrode arrays were maintained in the same position throughout the experiment.
      While the stimulus intensities were kept constantly in the normal clinical level
      (6 dB above EABR threshold), four stimulus rates of 200 (n=14), 400 (n=10), 1000
      (n=11), 2000 (n=10) pulses/s(PPS) were each delivered to bipolar electrodes in
      scala tympani of 45 guinea pigs for 2 h of acute electrical stimulation.
      Thresholds and wave I amplitudes of EABR were recorded for periods of 3 h
      following 2 h of acute stimulation. By comparing the pre-stimulus amplitudes of
      wave I in EABR with the post-stimulus ones(t test), the effect of high-rate
      electrical stimulation on excitability of the auditory nerve was assessed.
      RESULT: While the acute stimulus intensity was kept constantly in the normal
      clinical level (6 dB above EABR threshold), with comparison of pre-stimulus
      response with post-stimulus response of wave I, the latter increased by 20%, 30%,
      9%, 7% at each of the four different stimulus rates of 200, 2000, 400, 1000 PPS.
      CONCLUSION: Within the 3 h post-stimulus monitoring period after 2 h acute
      stimulation, no reduction but increase in EABR amplitude was observed using
      stimulus intensity of 6 dB above EABR threshold at four stimulus rates (200, 400,
      1000, 2000 PPS). Electrical stimulation presented at high rates of 1000 to
      approximately 2000 PPS with clinical intensity (6 dB above EABR threshold) did
      not result in the reduction of excitability of auditory nerve. These results
      supported to provide data for the envisaged introduction of a speech-processing
      strategy based on high stimulus rates.

PMID- 16108324
TI  - [Carboplatin-induced injury patterns of inner hair cells missing in chinchilla
      cochlea].
AB  - OBJECTIVE: To explore carboplatin-induced injury patterns of inner hair cells
      (IHCs) in cochlea of chinchilla, namely, when injury of IHCs occurs, what
      extension injury of IHCs exists at different time after drug administration,
      where maximal injury of IHCs locates on basal membrane and how long most IHCs
      lose after drug administration. METHOD: Carboplatin of moderate concentration
      (100 mg/kg) was used to inject peritoneally one time and animals were decapitated
      on schedule, surface preparations were made and cochleograms were obtained to
      observe injury of IHCs in the cochleae of chinchillas. RESULT: Loss of outer hair
      cells was not observed on basal membrane from 24 hours to 3 months after drug
      administration except one ear. The characteristic of IHCs injury patterns was
      found to be: (1) IHCs were intact at 24 hours after drug administration. IHCs
      injury was firstly observed within 3 days. (2) The maximal rate of IHCs injury
      located around boundary of turn one and turn two on basal membrane from 24 hours
      to 3 months. (3) IHCs injury began from boundary of turn one and turn two and
      extended to basal turn and apical turn gradually. Compared to apical turn, IHCs
      injury on basal turn occurred earlier and more severely. (4) Most IHCs lost in 3
      months. CONCLUSION: Carboplatin of 100 mg/kg unequally destroyed IHCs from
      different turns. Temporal variance of injury of IHCs from given turn is most
      likely due to their discrepant sensitivity to carboplatin.

PMID- 16108325
TI  - [Alteration of the auditory function and auditory nerve pathology in Guinea pigs
      with peripheral nerve demyelination].
AB  - OBJECTIVE: To study the auditory function and auditory nerve pathological changes
      of the experimental allergic neuritis (EAN) animal model in Guinea pigs. METHOD:
      To establish the animal model of EAN, heterologous myelin basic protein (MBP) of
      peripheral nerve was used to the immunize Guinea pigs. Serum anti-MBP-IgG levels,
      sciatic nerve conduction velocity (NCV), hearing thresholds and wave latencies,
      and pathological changes in auditory nerve, sciatic nerve and cochlea were
      observed. The immune lesions in inner ear were examined with
      immunohistochemistry. Auditory brainstem response (ABR) and compound action
      potential (CAP) were assayed weekly before and after immunization for a period of
      seven weeks. In the control group, antigen was replaced by the 0.9% saline.
      RESULT: Serum anti-MBP-IgG levels increased significantly in experimental group
      comparing with the control group (P < 0.01). Seiatic nerve conduction velocity
      decreased after immunization, as comparing with the control group (P < 0.01).
      Sciatic nerve and auditory nerve showed the existence of demyelination. There was
      significant increase of ABR and CAP thresholds and the latencies of wave I, III,
      V and N1 in experimental group when compared to the controls (P < 0.01), but no
      significant changes in inter-peak latencies of I-III, III-V were found( P >
      0.05). In addition, there were 4 Guinea pigs (8 ears) in which only appeared
      lengthened wave latencies with normal hearing thresholds. Immunohistochemistry
      indicated that antibodies to inner ear from the MBP-sensitized animals
      distributed in cochlear nerve, neurofiber of inner ear and spiral ganglion cells.
      Cochlear scanning electron microscopy showed the pathology of inner hair cell
      with stereociliary disorder and cytoplasmic protrusions. CONCLUSION: The results
      suggest that auditory nerve demyelination are involved in this experimental
      allergic neuritis animal model and sciatic nerve demyelination as well, and the
      auditory abnormalities are elicited. This animal model seems to be a promising
      one of auditory dysfunction due to demyelination disorders.

PMID- 16108326
TI  - [Applied anatomy of the perforating branches artery and its distally-based flap
      of sural nerve nutrient vessels].
AB  - OBJECTIVE: To investigate the distribution of the perforating branches artery of
      distally-based flap of sural nerve nutrient vessels and its clinical application.
      METHODS: The origins and distribution of perforating branches artery of distally
      based flap were observed on specimens of 30 adult cadaveric low limbs by
      perfusing red gelatin to dissect the artery. Among the 36 cases, there were 21
      males, 15 females. Their ages ranged from 6 to 66, 35. 2 in average. The defect
      area was 3.5 cm x 2.5 cm to 17.0 cm x 11.0 cm. The flap taken ranged from 4 cm x
      3 cm to 18 cm x 12 cm. RESULTS: The perforating branches artery of distally-based
      flap had 2 to 5 branches and originated from the heel lateral artery, the
      terminal perforating branches of peroneal artery (diameters were 0.6+/-0.2 mm and
      0.8+/-0.2 mm, 1.0 +/- 1.3 cm and 2.8 +/- 1.0 cm to the level of cusp lateral
      malleolus cusp). The intermuscular septum perforating branches of peroneal artery
      had 0 to 3 branches. Their rate of presence was 96.7%, 66.7% and 20.0%
      respectively (the diameters were 0.9 +/- 0.3, 1.0 +/- 0.2 and 0.8 +/- 0.4 mm, and
      their distances to the level of cusp of lateral malleolus were 5.3 +/- 2.1, 6.8
      +/- 2.8 and 7.0 +/- 4.0 cm). Those perforating branches included fascia branches,
      cutaneous branches, nerve and vein nutrient branches. Those nutrient vessels
      formed longitudinal vessel chain of sural nerve shaft, vessel chain of vein side
      and vessel network of deep superficial fascia. The distally-based superficial
      sural artery island flap was used in 18 cases, all flaps survived. CONCLUSION:
      Distally-based sural nerve, small saphenous vein, and nutrient vessels of fascia
      skin have the same origin. Rotation point of flap is 3.0 cm to the cusp of
      lateral malleolus, when the distally-based flap is pedicled with the terminal
      branch of peroneal artery. Rotation point of flap is close to the cusp of lateral
      malleolus, when the distally-based flap is pedicled with the heel lateral artery.

PMID- 16108327
TI  - [Applied anatomy of small saphenous vein and its distally-based sural nerve
      nutrient].
AB  - OBJECTIVE: To investigate the origin of small saphenous vein of distally-based of
      sural nerve nutrient vessels flap and its clinical application. METHODS: The
      origins of nutrient vessels of small saphenous vein and communicating branches of
      superficial-deep vein were observed on specimens of 30 adult cadaveric low limbs
      by perfusing red gelatin to dissect the artery. RESULTS: The nutrient vessels of
      small saphenous vein originated from the heel lateral artery, the terminal
      perforator branches of peroneal artery and intermuscular septum perforating
      branches of peroneal artery. There were 2 to 5 branches of such distally-based
      perforating branches whose diameters ranged from 0.6 to 1.0 mm. Those perforating
      branches included fascia branches, cutaneous branches nerve and vein nutrient
      branches. Those nutrient vessels formed a longitudinal vessel chain of clinical
      nerve shaft, vessel chain of vein side and vessel network of deep superficial
      fascia. The small saphenous vein had 1 to 2 communicating branches of superficial
      deep vein whose diameter was 1.7+/-0.5 mm, 3.4+/-0.9 cm to the level of cusp of
      lateral malleolus, and converged into the fibular vein. CONCLUSION: Distally
      based sural nerve, small saphenous vein, and nutrient vessels of fascia skin have
      the same region. The communicating branches of superficial-deep vein is 3 to 4 cm
      to the level of cusp lateral malleolus. These communicating branches could
      improve the venous drainage of the flap.

PMID- 16108328
TI  - [Application of free flaps in combined transplantation].
AB  - OBJECTIVE: To investigate the application of free flaps in combined
      transplantation and its clinical outcome. METHODS: From January 1991 to December
      2003, 56 cases of combined transplantation involving cutaneous or myocutaneous
      flaps were performed to repair extremely large soft tissue defects, large-sized
      skin and segmental bone defects and to simultaneously reconstruct the missing
      thumb and repair the associated skin defects in the first web space. Of the 56
      patients, 37 were males, 19 were females. Their ages ranged from 5 to 41, 27.6 in
      average. The transplants included latissimus dorsi myocutaneous flap, scapular
      flap, lateral femoral flap, big toe skin-nail flap, and fibula. To establish
      blood circulation in the transplants, the common vascular pedicle was anastomosed
      directly to the vessels in the recipient site in 35 cases but to the selected
      vessels in the healthy limb in 21 through a cross-bridge procedure. Results With
      failure in 2 cases of combined transplantation of latissimus dorsi myocutaneous
      flap and vascularized fibula, all the transplants survived well. In the 32 cases
      of long bone defects with successful repair, the transplanted fibula united with
      host bones 14.5 weeks after operation on the average. A mean follow-up of 28 (10
      128) months revealed that function in all cases was recovered, while one patient,
      who underwent a successful combined transplantation of latissimus dorsi
      myocutaneous flap and vascularized fibula, required amputation of the involved
      leg 3 years after repair because of the repeated ulcers in the toes. CONCLUSION:
      The application of free flaps in combined transplantation can lead to an
      effective repair of complicated tissue defects of the limb and to a successful
      reconstruction of the associated missing thumb.

PMID- 16108329
TI  - [Clinical experience of flap appliance in soft tissue defects of upper
      extremity].
AB  - OBJECTIVE: To discuss the advantages and disadvantages of flaps in the repair of
      soft tissue defects in upper extremity. METHODS: Based on the 2609 cases of flaps
      in 2512 patients from 1995 to 2004, the advantages and disadvantages of different
      sort of flaps, outcomes of treatment and indications of different soft of flaps
      were analyzed retrospectively. In the series, 2 089 pieces of the traditional
      flaps of different sorts were applied in 1992 patients, 474 pieces of the axial
      flaps of different sorts were applied in 474 patients, different sorts of free
      flaps were used in 46 patients. RESULTS: Follow-ups were done for 1 month to 9
      years (2.7 months in average). 2 531 flaps survived (97.01%); complete necrosis
      occurred in 10 flaps (0.38%); partial necrosis occurred in 68 flaps (2.61%). Of
      the 2089 traditional flaps, 46 had partial necrosis (2.2%); 687 needed flap
      revisions (32.9%). Of the 474 axial flaps, 28 had complete or partial necrosis
      (5.9%); 82 needed revisions (17.3%). Of the 46 free flaps, 4 had complete or
      partial necrosis (8.7%) and nearly all the anterolateral flaps of thighs needed
      revisions. CONCLUSION: Traditional flaps had the advantages of easy manipulation
      and the highest survival rate, however, also had the disadvantages of poor
      texture and many times of operations. The flap with a pedicle had the advantage
      of good texture, consistent artery, free-range arc, however, the venous
      congestion was its disadvantage, which impaired the survival of the reverse flap.
      Free flap had the advantage of good texture and abundant donor site, but
      complicate manipulation was its shortage. Axial Flap with a pedicle is the
      optional choice for repairing soft tissue defects in upper extremity.

PMID- 16108330
TI  - [Combined tissue transplantation for complicated hand injury].
AB  - OBJECTIVE: To investigate the effect of combined types in treating cases with 2
      to 5 tissues transplantation. METHODS: 305 cases treated from December 1989 to
      December 2002 were analyzed and summarized. 214 cases were constructed with 2
      combined tissues transplantation, the combined types were:toe combined flap,the
      second toe at both sides transplanted, 2 flaps combined transferred; 75 cases
      were constructed with 3 combined tissues transplantation, the combined types
      were: the second toe at both sides combined flap, 2 flaps combined toe, 3 flaps
      combined transferred; 11 cases were constructed with 4 combined tissues
      transplantation, the combined types were: 2 flaps combined 2 toes,1 toes combined
      3 flaps, 4 flaps combined transferred; 5 cases were constructed with 5 combined
      tissues transplantation, the combined type was: the wrap flap and the second toe
      with 1 vascular pedicle and another second toe combined bilateral femoris
      anterior flaps were transferred. The principles of repair were: the thumb was
      reconstructed first,the wrap round flap was used for the thumb's skin, the second
      toe transplantation was used for the thumb defect. The opposite toe was
      transferred to finger to reconstruct the pinch function. 1 or 2 flaps were
      selected for repair according to the area of damage. The anterolateral thigh
      flaps were used for the large areas and the lateral arm flaps were used for the
      small areas in selecting the donor area. RESULTS: Of the 722 tissues in 305
      cases, 14 of them were necrosis, in which the toe were 6 and the flap were 8,and
      other transferred tissues all survived, the survival rate of tissue
      transplantation was 98.1%. 251 cases were followed up for 1 year to 7 years (2. 6
      years in average). All the patients could care themselves in daily life. The
      pinch and opposition functions of the constructed thumbs and fingers were
      recovered, the two-point discrimination was 6 to 14 mm, but 2 cases recovered
      adduction function only because the thumb was 6 degree defect without the thenar
      muscle and did not fix the reconstructed thumb in opposite side in operation. All
      transplanted flaps recovered protecting sensory with S2, 56 flaps required
      plastic operation because of their swelling appearance. The donor areas gained
      primary stage heal in 285 cases, 20 cases gained secondary stage heal, in which
      part grafted skin necrosis in donor of wrap round flap were 12 cases, the distal
      of donor big toe necrosis were 2 cases and grafted skin necrosis in donor of
      anterolateral thigh flap were 8 cases and skin grafted were successful.
      CONCLUSION: Different combined types can be used according to the traumatic
      situation. Surgical operation and early rehabilitation is conducive to the final
      function. Combined tissue transplantation is the best way to repair complicated
      hand injuries.

PMID- 16108331
TI  - [Tissue flap transferring for wound repair of the clavicle].
AB  - OBJECTIVE: To investigate the result of tissue flap transferring for wound repair
      of the clavicle. METHODS: From 1994 to 2000, 3 patients (1 with clavicle
      osteosynthesis, 1 with chronic clavicle osteomyelitis, and 1 with radioactive
      ulcer in clavicular region accompanied by chronic osteomyelitis of clavicle) were
      reconstructed with turnover adipofascial flap, myocutaneous flap of pectoris, and
      myocutaneous flap of latissimus dorsal respectively. The outcome was observed.
      The operation principles of tissue flaps transferring for wound repair of the
      clavicle were summarized. RESULTS: Follow-ups were done for 2 months to 7 years.
      All tissue flaps survived well and the wounds in clavicular region were healed
      well. There was no recurrence of chronic clavicle osteomyelitis. CONCLUSION:
      Turnover adipofascial flap, myocutaneous flap of pectoris and latissimus dorsal
      are often used for wound repair of the clavicle. Most of the wounds of the
      clavicle can be repaired by turnover adipofascial flap. Myocutaneous flap of
      pectoris and latissimus dorsal are more suitable for wound repair with chronic
      clavicle osteomyelitis. In the case of radioactive ulcer of the clavicular
      region, myocutaneous flap of latissimus dorsal transposition is a better
      alternative for wound repair.

PMID- 16108332
TI  - [Study on the application of arm medial fascio-cutaneous flap pedicled with
      cutaneous nerve and nutrient vessel].
AB  - OBJECTIVE: To investigate the application of arm medial fascio-cutaneous flap
      pedicled with cutaneous nerve and nutrient vessel. METHODS: From February 1999 to
      December 2004, 18 cases of skin and soft tissue defect in axillary region, elbow
      and forearm were treated with arm medial fascio-cutaneous flap pedicled with
      cutaneous nerve and nutrient vessel. Arm medial fascio-cutaneous flap was
      directly transferred in 3 cases, adversely transferred in 15 cases. The flap area
      was 4.5 cm x 8.5 cm. RESULTS: Vein circulation crisis was observed in 3 cases. Of
      the 3 cases, 1 was necrosis and the other 2 by decompressing small vein were
      saved. The rest 15 cases survived. The period of follow-up was 3 to 30 months.
      Flap was satisfactory in appearance and function. CONCLUSION: Arm medial
      fasciocutaneous flap pedicled with cutaneous nerve and nutrient vessels can be
      directly or adversely transferred to repair adjacent soft tissue defect.

PMID- 16108333
TI  - [Clinical application of second dorsal metacarpal artery flap in hand surgery].
AB  - OBJECTIVE: To summarize the clinical experiences of various types of the second
      dorsal metacarpal artery (SDMA) flap for hand reconstruction. METHODS: From 1988
      to 2003, 139 SDMA flaps were transferred for hand injuries. The flaps were used
      in 5 types according to vascularization and technique in
      transplantation:orthograde pedicled island SDMA flaps in 37 cases (cutaneous in
      24 and teno-cutaneous in 13), retrograde pedicled island SDMA flaps in 25 cases
      (cutaneous in 19 and teno-cutaneous in 6), double pivot SDMA flaps in 36 cases
      (cutaneous in 28 and tenocutaneous in 8), distal perforator branch pedicled flaps
      in 19 cases (cutaneous in 16 and composite in 3), free SDMA flaps in 22 cases
      (cutaneous in 15 and composite in 7). The skin islands were 3.0 cm x 1.5 cm to
      6.3 cm x 5.0 cm in size. RESULTS: Of the 139 flaps, 135 flaps survived
      completely, 3 survived partially, and 1 failed in the operation because of
      intractable vascular spasm. Follow-up was done in 116 cases for 12 to 57 months.
      The flap had good texture and color match. The two-point discrimination was 5 to
      9 mm in 78 sensate flaps, while it was 10 to 15 mm in 38 nonsensate flaps. In 21
      tenocutaneous flaps, the TAM score of range of motion was 60% to 70% of the
      healthy side. CONCLUSION: The SDMA flap has a constant and reliable vessel and a
      thin, pliable, and good-quality skin. It is versatile in creating composite
      flaps. It is a good flap resource for hand and finger reconstruction.

PMID- 16108334
TI  - [Bilateral three-toe transplantation with dorsalis pedis flap and first web space
      flap for damage injury in the hands].
AB  - OBJECTIVE: To discuss the surgical method and effect of repair of damage injury
      in the hands. METHODS: Of the 29 cases, 22 were males, 7 were females. Their ages
      ranged from 15 to 31. The size of defect areas ranged from 18 cm x 8 cm to 22 cm
      x 10 cm. Along with dorsalis pedis flap, lateral hemi-pulp flap was taken from
      great toe and first web space flap. The second toe was taken from one foot to
      reconstruct the thumb, second and third toe from another foot was used to
      reconstruct two fingers. The dorsalis pedis flaps were used to cover palm and
      dorsum of hand. The lateral hemi-pulp flaps from great toe and first web space
      flaps were used to reconstruct first web space of hand. RESULTS With the 58
      combined flaps, 29 thumbs and 58 fingers were reconstructed. Follow-ups was done
      for 1 to 8 years. All the thumbs and fingers of 29 hands were reconstructed.
      Their shape and function were well recovered. CONCLUSION: This new surgical
      method is effective in preserving the function of injured hand. The function of
      the injured hands can be preserved by this surgical method, therefore this method
      is optimal.

PMID- 16108335
TI  - [Study on the effect of pedicle skin flap of subdermal vascular plexus on
      repairing the hand injury].
AB  - OBJECTIVE: To summarize the operation opportunity and recovery effect of pedicle
      skin flap of subdermal vascular plexus on repairing the raw surface of hand
      injury. METHODS: From January 1999 to June 2004, the thoracic or abdominal
      pedicle skin flap of subdermal vascular plexus was used to repair the raw surface
      of hand with defect of skin and soft tissue in 22 patients with hand injury. 17
      cases were males, 5 cases were females, the ages ranged from 9 to 42. The causes
      of hand injury including avulsed wound in 12 cases, mangled injury in 2 cases,
      hot crush injury in 5 cases, electric burn in 3 cases; 13 cases needed emergency
      operation, 9 cases needed operation in 3 to 7 days. The thoracic or lower
      abdominal flap was selected depending on the raw surface of hand injury.
      Subcutaneous fat was trimmed and retained the thickness of 2 to 4 mm. The skin
      flap was designed into 2 to 3 leaves to form several pedicle skin flap of
      subdermal vascular plexus, which were used to repair defect of skin and soft
      tissue of several fingers. The defect site of skin and soft tissue of hand were
      put into flap. RESULTS: A little of skin flap in distal end became necrosis in 1
      case after operation, but recovered fully after changing dressing to the raw
      surface. The rest of the flaps all survived. Follow-up was conducted 3 months to
      2 years. The pedicle skin flap was living,the skin of the recipient site was
      smooth and integrated, color and luster was satisfactory and texture was soft.
      The disrupted pedicle skin flap needed no trimming. The hand function was
      significantly recovered. CONCLUSION: To repair the defect of skin and soft tissue
      in the hand injury by using thoracic or lower abdominal pedicle skin flap of
      subdermal vascular plexus has the forte of shorter course of treatment and better
      functional recovery and good outlook. It is one of the ideals for repairing the
      hand injury with defect of skin and soft tissue.

PMID- 16108336
TI  - [Turnover adipofascial flap for wound repair of the extremities].
AB  - OBJECTIVE: To introduce the clinical experience of local distally based turnover
      adipofascial flap for small to medium size wound of the extremities. METHODS:
      From 1994 to 2003, 33 cases of distally based longitudinal neuro-veno
      adipofascial turnover adipofascial flap (axial perforator pattern in 26, random
      pattern in 7) were transferred in the forearm (19) and lower leg (14). These
      flaps were all raised in the forearm or lower leg as local flaps. The length
      (pedicle plus flap) was 9 to 18 cm and the width was 3 to 4 cm, with L/W ratio of
      3 to 5 : 1. After transferring by 180 degrees turnover, a split-thickness skin
      graft was used to cover the fascia surface. RESULTS: All the 33 flaps survived.
      The donor sites were closed directly, and the recipient sites were covered with
      full- or split-thickness skin grafts. Both donor and recipient sites healed
      primarily. CONCLUSION: Turnover adipofascial flap is a simple and reliable method
      for small to medium size wound of the extremities.

PMID- 16108337
TI  - [The effect of fibula flap graft on the restoration of the extremities with
      traumatic compound tissue defects].
AB  - OBJECTIVE: To evaluate the clinical effects of fibula flap grafts on the repair
      of the extremities with traumatic compound tissue defects. METHODS: In 12 cases,
      the fibula flap grafts were employed to restore the extremities with traumatic
      compound tissue defects. Of the 12 patients, 9 were males, 3 were females; their
      ages ranged from 12 to 45. There were 2 cases of tibia defect combined with
      fibula fracture, 2 cases of tibia defect, 2 cases of radius defect, 3 cases of
      ulna defect, 1 case of calcaneus defect, and 2 cases of first-metatarsus defect.
      The bone defect length ranged from 4.2 to 10.6 cm, 7.8 cm in average. The skin
      defect area ranged from 10.0 cm x 4.5 cm to 27.0 cm x 15.0 cm. The free
      transplantation of fibular flaps were used in 9 cases, the lapse operation were
      used in 2 cases, retrograde shift were used in 1 case. RESULTS: Post-operational
      vein crisis and common peroneal nerve traction injury were observed in category
      mentioned above respectively. All the 12 fibula flaps survived after proper
      treatments such as removal of great saphenous vein. Follow-ups were done for 6 to
      24 months. Both the transferred fibula and the recipient broken end reflected
      bones were healed. Four patients underwent the second-phase reconstruction
      operation of tendon moving power. One wrist and 1 ankle underwent arthrodesis in
      3 to 6 months. All the effects were satisfactory. CONCLUSION: The fibula flap
      grafts provide a relatively better alternative to repair the extremities with
      long bone compound tissue defects. In addition, the sensory function
      reconstruction of fibula flaps should be given full attention.

PMID- 16108338
TI  - [Resection and reparation of heel with malignant melanoma].
AB  - OBJECTIVE: To investigate the surgical resection and reparation of heel with
      malignant melanoma. METHODS: Eight patients with malignant melanoma were treated
      from May 2001 to December 2003. The patients included 5 males and 3 females, and
      their ages ranged from 28 to 56 years. All lesions were located in the heel and
      were proved by pathological examination. According to Breslow classification,
      there were 2 cases of Grade I, 5 cases of Grade I, and 1 case of Grade II. Local
      extensive resection was performed in all cases. Lateral pedal skin flap, plantar
      medial artery island skin flap, and retrograde skin flap supplied by sural
      nutrition blood vessel were respectively applied in the reparation according to
      the size of heel soft tissue defect. The treatment with interferon was delivered
      before and after the operation. RESULTS: The surgical reparation was successful
      in all 8 cases. The postoperative follow-up was conducted from 18 months to 4
      years. All patients remained alive and no tumor recurrence was observed.
      Considering the recovery of the function and sense, the best result was acquired
      with plantar medial artery island skin flap and lateral pedal skin flap, good
      with retrograde skin flap supplied by sural nutrition blood vessel. CONCLUSION:
      Local extensive resection is essential for the heel with malignant melanoma.
      Reparative reconstruction should be made on negative operative margin.
      Satisfactory clinical outcome is achieved by using lateral pedal skin flap,
      plantar medial artery island skin flap, and retrograde skin flap supplied by
      sural nutrition blood vessel.

PMID- 16108339
TI  - [Perforator-based flap for repair of gluteal-sacral defects].
AB  - OBJECTIVE: To investigate the operative technique and clinical effect of
      perforator-based flap for repair of gluteal-sacral skin defects. METHODS: A new
      perforator-based flap derived from the gluteal, parasacral and the lumbar
      arteries was used to repair skin defects of gluteal-sacral region caused by
      trauma or pressure sore. The flap areas ranged from 6 cm x 5 cm to 19 cm x 11 cm,
      the diameter of perforating vessel ranged from 1.3 to 2.1 mm, the length of free
      perforating vessel pedicle ranged from 2.5 to 4.5 cm. RESULTS: All the flaps
      survived and the wound gained primary healing. All the patients were followed up
      for 6 to 24 months. The colour and texture of the flaps were excellent, the
      configuration was satisfactory and there was no ulcer recurrence. CONCLUSION:
      This new type of flap is characterized by delicate design, easy dissection,
      reliable blood supply, no sacrifice of the underlying muscle and no requirement
      skin graft for donor site closure. It is an optimal method in repairing soft
      tissue defects of the gluteal-sacral region.

PMID- 16108340
TI  - [Osteomyocutaneous latissimus dorsi scapular combined flap with vascularized rib
      to repair the large defect of tibia].
AB  - OBJECTIVE: To design a combined flap of subscapular axis including vascularized
      lateral scapular, rib and latissimus dorsi to repair the large defect of tibia.
      METHODS: The patient was a 39-year-old man who got a posttraumatic 12 cm defect
      of tibia after primary debridement and external fixation because of open fracture
      5 months ago. There was a 12 cm x 6 cm scar involved the proximal medial segment
      of tibia. After resection of scar and fibular tissue over the bone defect floor,
      a latissimus dorsi myocutaneous flap 14 cm x 5 cm pedicled with subscapular
      artery-thoracodorsal artery, a flap 12.5 cm on the outside of the scapular
      pedicled with thoracodorsal artery, and 6th rib flap 13 cm by serratus were
      prepared. The tibialis posterior and saphenous vein were used for anastomosis. A
      proximal anatomic plate was applied to the fixation of tibia. RESULTS: The
      compound flap survived the operation. The follow-up period was 2 years. Bone
      union occurred 6 months after operation. CONCLUSION: This combined flap is
      successful and can provide alternative to the resolution of large defect of
      tibia.

PMID- 16108341
TI  - [The optimization of the method of culturing neural stem cells in neonatal rat
      brain].
AB  - OBJECTIVE: To establish a better method of isolating and culturing of neural stem
      cells (NSCs) in neonatal rat brain. METHODS: Tissue of brain was isolated from
      neonatal rats. Different medium and culture concentration were used to culture
      NSCs of neonatal rat. The culture concentration used were 1 x 10(4), 1 x 10(5), 1
      x 10(6), and 1 x 10(7)/ml respectively. Ingredient of medium was classified into
      group 1 to 8 respectively according to whether to add 2% B27, epidermal growth
      factor (EGF) and basic fibroblast growth factor (bFGF) as well as the difference
      in culture concentration. The cells were induced to differentiate as to be
      confirmed as NSCs, and then were checked by phase contrast microscopy and
      identified by immunocytochemistry. RESULTS: The cells isolated and cultured
      gathered into neurospheres. The cells were capable of proliferating and
      maintaining long-term survival in vitro. The cells could be differentiated into
      neurons and glia. It was to the benefit of the survival of NSCs to add 5% fetal
      bovine serum(FBS) into the medium at the beginning of the culturing. When 10% FBS
      was added into the medium, the neurospheres differentiated quickly. When
      concentration 1 x 10(6)/ml was used, the growth rate of the cells was the highest
      of all the concentrations. Reasonably higher cell concentration promoted the
      proliferation of NSCs. It was necessary to add 2% B27, EGF, and bFGF into the
      medium. The cells had the best growth when 2% B27, 20 ng/ml bFGF and 20 ng/ml EGF
      were added into the culture medium. EGF and bFGF had cooperative effect.
      CONCLUSION: A better method of isolating and culturing of NSCs in neonatal rat
      brain is established and the foundation for future research is laid.

PMID- 16108342
TI  - [Correction of enophthalmos deformity caused by orbital blow-out fractures using
      medpor implantation].
AB  - OBJECTIVE: To study the surgical reconstruction for correction of enophthalmos
      deformity caused by orbital blow-out fractures. METHODS: From December 1996 to
      March 2004, 56 cases of enophthalmos deformity caused by orbital blow-out
      fracture were repaired. There were 37 cases diplopia, 35 cases with worsened
      visual acuity than pre-trauma. Typical sub-ciliary incision was employed to
      expose the fractured area. The dissection was done beneath the medial and
      inferior orbital periosteum. The fracture areas were exposed and the tissues
      protrusion to maxillary sinus were released through the space between fractured
      bones. After the medial and inferior orbital walls and orbital floors were
      exposed,the herniated orbital contents were released and reduced to the orbital
      cavity. The fractured orbital walls were repaired precisely with Medpor which
      were fixed to the area beneath the periosteum with 2 plates at least. RESULTS:
      All 56 cases of enophthalmos deformity caused by orbital blow-out fracture
      repaired with this technique recovered well and their facial appearance improved
      greatly. With a follow-up ranged from 2 months to 5 years, the degree of
      enophthalmos stabilized at within 2 mm, no relapse and other complications
      occurred. Of 34 patients with diplopia, 27 were improved. Of the 35 cases with
      worsened visual acuity, 9 were improved with different degree. No diplopia or
      visual acuity worsening occurred. CONCLUSION: It is safe and effective to correct
      the orbital blow-out fractures. The earlier it is repaired, the better the effect
      will be. Medpor with its advantages like better histocompatibility, easier
      sculpturing, moderate hardness, lower absorptivity, fewer complications and
      permanence effect is the preferable implantation material for correcting
      enophthalmos deformity.

PMID- 16108343
TI  - [Clinical study on double contrast CT diagnosis of traumatic anterior shoulder
      instability].
AB  - OBJECTIVE: To evaluate the clinical importance of double contrast CT diagnosis of
      traumatic anterior shoulder instability. METHODS: Forty-eight patients underwent
      double contrast CT scan. With the guide of CT scan, anterior arthrocentesis of
      the shoulder was performed and 4 ml of 76% urografin was injected into the joint
      and then 10 ml of filtrated air was injected. The patients were examined by
      SOMATOM CR Systematic CT. The results of double contrast CT of the 48 patients
      were divided into I, II and III degree according to the CT results related to
      their injury history, clinical symptoms, signs and operation findings. RESULTS:
      The patients had no complaint after the CT examination except for 3 patients, who
      had slight pain within 2 days after CT examination. The results of double
      contrast CT were as follow: I degree: 9 patients, II degree: 22 patients, and III
      degree: 17 patients. All patients with I degree injuries were treated with
      rehabilitation program. The patients with II degree injuries were mainly treated
      with rehabilitation program, but took much longer time. The patients with III
      degree injuries were suggested to be treated with surgery. CONCLUSION: To divide
      the results of double contrast CT into I, II and III degree not only reflects the
      severity of traumatic anterior shoulder instability but provides information for
      the treatment of the instability.

PMID- 16108344
TI  - [Reconstruction of the unstable pelvic fractures].
AB  - OBJECTIVE: To investigate the clinical characteristics of unstable pelvic
      fractures and to find out an alternative for the treatment. METHODS: From October
      2000 to June 2004, fifty-six patients with unstable pelvic fractures were treated
      by open reduction and pelvic-reconstructed plate fixation to recover the
      anatomical structure of pelvis and acetabulum. According to Tile classification,
      33 cases were type B (15 cases were Tile B1, 11 cases were Tile B2, 7 cases were
      Tile B3); 23 cases were type C (10 cases were Tile C1, 8 cases were Tile C2, 5
      cases were Tile C3). RESULTS: The 56 cases were followed up 12 to 68 months (26
      months in average). All cases with fractures got healed during 3 to 6 mouths.
      According to the Majeed evaluation, 40 cases were excellent, 11 cases were good,
      4 cases were fair, and only one case was a failure. The rate of excellence and
      goodness was 91.07%. The pelvic abnormality was rectified; partial patients felt
      light pain in iliac scar. CONCLUSION: The choice of the proper operative approach
      and pelvic-reconstructed plate fixation by allowing for fracture classification
      is a good and dependable means for treating unstable pelvic fractures.

PMID- 16108345
TI  - [Microsurgical repair of bone defect of the first carpometacarpal joint].
AB  - OBJECTIVE: To assess the clinical effect of microsurgical treatment for bone
      defect of the first carpometacarpal joint. METHODS: From February 2001 to August
      2004, the pedicled free graft of second tarsometatarsal joint was transplanted to
      repair bone defect of the first carpometacarpal joint according to the shape and
      area of tissue defect of hand in 3 patients. The dorsalis pedis flap was
      simultaneously used to repair soft tissue defect of carpometacarpal joint and the
      big thenar in 2 cases. The donor site was sutured directly or covered by
      intermediate thickness skin flap. RESULTS: The vessel of the bone flap had
      constant anatomical location, the operation procedure was easy. Moreover it had
      minimal effect on donor, the flap of dorsalis pedis could be used to repair soft
      tissue defect in this area. Three cases were followed up 1 to 2 years. The shape
      of the reconstituted thumb was normal. The healing time of clinical fracture of
      the first carpometacarpal joint was 2 to 3 months. The function recovery of the
      reconstituted thumb was satisfactory. CONCLUSION: It is an effective method to
      repair bone defect of the first carpometacarpal joint with the pedicled second
      tarsometatarsal joint graft.

PMID- 16108346
TI  - [Extendible replacement of the distal femur in the treatment of osteosarcoma in
      growing individuals].
AB  - OBJECTIVE: To investigate the possibility of using extendible distal femoral
      replacements in the treatment of osteosarcoma in growing individuals. METHODS:
      From December 1999 to March 2003, 3 cases (2 were type II B, 1 was type II A)
      with osteosarcoma were treated by extendible distal femoral replacements. Of the
      3 cases, 2 underwent prosthesis extention operation, 1 was not operated. RESULTS:
      After the removal of tumor, the extremities of 2 patients were shortened by 4 to
      5 cm within 2 to 3 years. After the lengthening procedure, the affected
      extremities were of equal length to the unaffected extremities and no drag
      symptoms of blood vessel and nerves were observed. Follow-up was done for 2
      months to 3 years. There was no aseptic loosening. The function of joints was
      fairly good. CONCLUSION: Extendible distal femoral replacements is an easy,
      convenient, and effective way to treat osteosarcoma.

PMID- 16108347
TI  - [The study of interaction between the osteoblast and bio-derived material by
      detecting the gene expression].
AB  - OBJECTIVE: To study the gene expressions of human osteoblasts during the
      construction of tissue engineered bone with the bio-derived material. METHODS:
      The fetal osteoblasts were used to construct tissue engineered bone with the bio
      derived material and then were cultured 2, 4, 6, 8 and 10 days in vitro. Real
      time PCR analysis indicated that Cbfa 1, Osterix, Collagen type I, osteocalcin
      (OC) and Integrin alpha5 and beta1 were present in osteoblasts with bio-derived
      materials. Results The change of Cbfa1 was consistent with the change of Osterix.
      On 2nd day and 8th day, the expression of Osterix in experimental group was
      higher than that in control group, P<0.05. Collagen type I's change was
      consistent with change of OC expression, and its expression was higher in
      experimental group than that in control group on 2nd, 4th, 6th and 8th day. The
      Integrin expression was high all along. Conclusion The important genes can be
      expressed normally by integrating osteoblasts with bio-derived scaffolds. As
      skeleton tissue engineering scaffold, the bio-derived bone is conducive to keep
      the osteoblast's phenotype and differentiation with osteo-conductive ability. The
      osteoblast can enter proliferation stage favorably and the scaffold materials
      exert no effects on it. Bio-derived bone can also supply more space for cells to
      proliferate. The bio-derived materials promote osteoblasts adhesion.

PMID- 16108348
TI  - [Experimental study of tissue engineered bone with cryopreservation on healing of
      bone defects].
AB  - OBJECTIVE: To investigate the effect of tissue engineered bone with
      cryopreservation on healing of bone defects and to explore feasibility of
      cryopreservation for tissue engineered bone. METHODS: Tissue engineered bones
      were constructed with osteoblasts being seeded onto bio-derived materials made
      from fresh human bones,and they were preserved at 4 degrees C and - 196 degrees C
      for 3 months and 6 months respectively. They were applied to repair segmental
      bone defects of rabbit's radius while the tissue engineered bone without
      cryopreservation and bio-derived materials were brought into control groups. The
      experiment was divided into groups A3, A6, B3, B6, C and D (group A3: tissue
      engineered bones were preserved at 4 degrees C for 3 months; group A6: tissue
      engineered bones were preserved at 4 degrees C for 6 months; group B3:tissue
      engineered bones were preserved at --196 degrees C for 3 months; group B6:tissue
      engineered bones were preserved at - 196 degrees C for 6 months; group C: tissue
      engineered bones without cryopreservation; group D: bio-derived materials).
      Macroscopical and histological examination were done at the 2nd, 4th, 6th, 12th
      weeks, X-ray examination was done at the 6th, 12th weeks and biomechanics were
      determined at 12th weeks after operation respectively. RESULTS: Macroscopical
      observation showed no significant differences among group A3, A6, B3, B6 and C,
      but less new bone formation and more obvious boundary in group D were observed.
      Histological observation showed more collagen and new bone around the edge of
      implant of group A3, A6, B3, B6 and C than group D, and histological evaluation
      showed significant differences between group D and other groups (P <0.05).
      Radiographic observation showed no absorbability of the implant cortex and less
      new bone formation in group D, but the unity between implant and host bone,
      medullary cavity reopened, disappearance of fracture line and fine bone modelling
      were observed in other groups at 12 weeks after operation. Biomechanics between
      group D and other groups showed significant differences (P< 0. 05). CONCLUSION:
      Cryopreservation (4 degrees C and - 196 degrees C) were capable of preserving
      tissue engineered bone for long time, and tissue engineered bone with
      cryopreservation has significant effect on healing of bone defects. The methods
      fit clinical application.

PMID- 16108349
TI  - [Elementary evaluation of small intestinal submucosa and polypropylene mesh used
      for repairing abdominal wall defect in rats].
AB  - OBJECTIVE: To compare the effect of small intestinal submucosa (SIS) and
      polypropylene mesh (PPM) on repairing abdominal wall defects in rats, and to
      probe into the feasibility of using SIS to repair the abdominal wall defects.
      METHODS: 100 SD rats (50 males and 50 females)were randomly divided into 2 groups
      (n = 50). Their weight ranged from 200 to 250 g. Full thickness abdominal wall
      defects (2 cmX 2 cm) were created by surgery and were repaired with SIS and PPM
      respectively. At different postoperative time (1st, 2nd, 4th, 8th and 12th week),
      animals were sacrificed to make histological observation. The tensile strength
      and the development of adhesions were measured and observed. RESULTS: 95 animals
      survived and were healthy after surgery. No inflammatory response and obvious
      immunoreaction were observed in both groups. One week after operation, the
      tensile strength of abdominal wall in SIS group (204.30+/-5.13 mmHg) was lower
      than that in PPM group(240.0+/-10.0 mmHg) at 1st week (P<0.05), and there were no
      difference at 4th, 8th, 12th week. Adhesions were more marked in PPM group than
      that in SIS group (P<0.05). CONCLUSION: Both SIS and PPM are histologically
      compatible when used in rats and can maintain sufficient tensile strength. SIS is
      superior to PPM in regards to tissue compatibility and adhesion formation.

PMID- 16108350
TI  - [Incipient establishment of human bone marrow mesenchymal stem cells bank].
AB  - OBJECTIVE: To investigate the possibility of establishing the human bone marrow
      mesenchymal stem cells (hMSCs) bank as to provide an alternative source for the
      seed cells of tissue engineering. METHODS: The cell surface antigens of the
      purified, expanded hMSCs and the ones following cryopreservation were detected by
      flow cytometry, cultured in a special medium to induce the osteogenic and
      chondrocytic differentiation. Morphology was studied by light and electronic
      microscopes. The detection of alkaline phosphatase, collagen type I, osteocalcin,
      and collagen type II were also performed by immunochemistry and molecular
      biology. RESULTS: The phenotype and expansion possibility of hMSCs after
      cryopreservation were remained. It could expand for 10 generations. The doubling
      time was 40 h. CONCLUSION: The bank of hMSCs is incipiently established and can
      provide eligible seed cells for tissue engineering.

PMID- 16108351
TI  - [Modification of Heron's technique for cervical heterotopic cardiac
      xenotransplantation].
AB  - OBJECTIVE: To improve the Heron's technique for heterotopic cardiac
      transplantation in rats by cuff vessel anastomosis in some aspects and
      successfully establish the simplified model of cervical cardiac
      xenotransplantation from guinea pigs donor to SD rats recipients. METHODS: The
      donors were 64 male guinea pigs, whose weight ranged from 250 to 350 g; the
      recipients were 64 male SD rats, whose weight ranged from 300 to 350 g. The
      guinea pigs donor's ascending aorta and pulmonary artery were anastomosed to SD
      rats recipient's right common carotid artery and external jugular vein
      respectively with a self-made "sleeve" anastomosis. The modified cuff technique
      of heterotopic grafting is described in detail. RESULTS: 64 consecutive
      successful transplantations have been performed by single surgeon were done with
      negligible operative risk. No anastomosis leakage nor vessel obstruction. The
      total time of surgical procedure were 45 to 60 minutes. The new technique allowed
      vascular anastomoses to be completed in 2 to 5 minutes. The total cold ischemia
      time for donor heart was 14 minutes in average. CONCLUSION: This modified Heron's
      technique was a simple, economical, practicable, reliable and high reproducible
      model can be operated by surgeons with minimal training in microvascular surgery,
      and be applied to various transplantation immunological studies.

PMID- 16108352
TI  - [Study on the methods of promoting the injectability of calcium phosphate
      cement].
AB  - OBJECTIVE: To study the methods of promoting the injectability of calcium
      phosphate cement. METHODS: Evaluation methods of bone cements, injectability and
      methods of promoting injectability were reviewed by extensive investigating of
      latest literatures. RESULTS: It was very important to improve the injectability
      of calcium phosphate cement. Commonly used methods to evaluate the injectability
      included testing injectability coefficient, pushing force and injection pressure.
      Injectability of calcium phosphate cement were promoted by increasing
      liquid/solid ratio, modulating the component of solid or liquid phase, and adding
      various additives. CONCLUSION: Promoting the injectability of calcium phosphate
      cement is the clinical requirement.

PMID- 16108353
TI  - [Artificial transcription factors as tools for gene expression manipulation].
AB  - In this new era of the genome, the complete sequences of various organisms (from
      the simplest to the most complex such as human) are now available, which provides
      new opportunities to study biology and to develop therapeutic strategies. But the
      paucity of research tools that manipulate specific genes in vivo represents a
      major limitation of functional genomic studies. In nature, the expression of
      genes is regulated at the transcriptional level primarily by proteins that bind
      to nucleic acids. Many of these proteins, which are termed transcription factors,
      are typically consist of two essential yet separable modules: DNA-binding domain
      (DBD) and effector domain (ED). Attempts to control the gene expression by
      artificial transcription factors are based on the application of this rule. Among
      the many naturally occurring DNA-binding domains, the Cys2-His2 zinc-finger
      domain has demonstrated the greatest potential for the design of novel sequence
      specific DNA-binding proteins. Each zinc finger domain, which comprises about 30
      amino acids that adopt a compact structure by chelating a zinc ion, typically
      functions by binding 3 base pairs of DNA sequence. Several zinc fingers linked
      together would bind proportionally longer DNA sequences. Ideally, these
      artificial DNA binding proteins could be designed to specifically target and
      regulate one single gene within a genome as complex as that found in human. Such
      proteins would be powerful tools in basic and applied research.

PMID- 16108354
TI  - [Recent advances on the structure and catalytic mechanism of hydrogenase].
AB  - Hydrogenases are enzymes that catalyse the oxidation of hydrogen and the
      reduction of protons. It plays an important role in the process of biohydrogen
      production. According to the metal atoms within hydrogenase, it can be classified
      as NiFe-hydrogenase, Fe-hydrogenase and metal-free hydrogenase. The overwhelming
      majority of hydrogenases are metalloenzymes. The metal atoms are involved in the
      forming of active site and [Fe-S] clusters. The active site directly catalyzes
      the reduction of protons and the oxidation of hydrogen. The [Fe-S] clusters are
      involved in the transport of electrons between the H2-activating site and the
      redox partners of hydrogenase. Presently, the crystal structures of NiFe
      hydrogenase and Fe-hydrogenase from a few kinds of microorganism have been
      revealed. The metal-free hydrogenase, characterized by the absence of [Fe-S]
      cluster and the presence of an iron-containing cofactor, shows a great diversity
      comparing with those of NiFe-hydrogenases and Fe-hydrogenases. Recent progress
      have also indicated the mechanisms of activation.

PMID- 16108355
TI  - [Soluble expression of recombinant human apoliprotein A-I-Milano in Escherichia
      coli].
AB  - Apolipoprotein A-I-Milano(AIM), a natural variant, not only inhibits the
      initiation and progression of atherosclerosis, but also makes the preexisting
      atherosclerotic lesions regress. AIM gene, at which N-terminal codens were
      optimized, was subcloned into the expression vector of pET22b. Recombiant
      plasmids were transformed into E. coli strain BL21 (DE3) and induced with IPTG.
      The expressed apoliprotein A-I-Milano was soluble in E. coli and was about 38% of
      total cell lysate. Purified by Butyl Sepharose 4F. F hydrophobic chromatography
      and Q Sepharose H.P. anion exchange chromatography, followed by ultrafiltration
      with Vivaspin 20 (30 000MW), AIM monomer was obtained in a purity of more than
      95%. Activity assay of binding of AIM monomer to lipid indicates that association
      of AIM monomer with DMPC is slower than normal apoA-I but DMPC number associated
      by AIM monomer is more than by apoA-I. This results will be important for
      studying structure, function of AIM, specially clinical application.

PMID- 16108356
TI  - [The construction of recombinant AAV vector expressing HSVtk gene controlled by
      Tet-On and the detection of its activity].
AB  - In order to investigate the application of recombinant adeno-associated virus
      (rAAV) vector containing Tet regulation system and HSVtk gene in cancer gene
      therapy, pAAV/TRE/HSVtk/Tet-On was constructed and identified with PCR and
      restriction enzyme digestion. Packaging cells HEK293 were cotransfected with
      plasmids pAAV/TRE/HSVtk/Tet-On, pAAV-RC and pAAV-helper to produce infectious
      rAAV, and CsCl2 densitygradient centrifugation method was performed for
      purification and concentration of rAAV. The viruses were then transduced into MCF
      7 cells. The results of dot blot hybridization indicate that the rAAV can
      transfer the target gene into MCF-7 cells. MTT assay showed that GCV could kill
      AAV-infected MCF-7 cells under the induction of Dox. The data demonstrated that
      rAAV containing Tet regulation system and HSVtk gene was successfully obtained,
      and could be used for further investigation of in vivo and in vitro experiments.

PMID- 16108357
TI  - [Subcellular localization and tissues expression profile of hGPCRc: an orphan G
      protein-coupled receptor].
AB  - As a member of orphan G protein-coupled receptors (oGPCRs), hGPCRc was cloned
      from human colon tissue and analyzed by bioinformatic softwares. It was showed
      that the corresponding amino acids of hGPCRc formed seven-transmembrane domains
      as the key characteristic of GPCRs. Then, the recombinant GFP-hGPCRc was
      constructed by fussing hGPCRc into pEGFP-N1 carrying green fluorescent protein
      (GFP) gene, and CHO-K1 cells were subsequently transfected with the GFP-hGPCRc or
      pEGFP-N1. The green fluorescence protein expression in the two different
      transfected cells was observed under the laser scanning confocal microscopy
      (LSCM). It was showed that green fluorescence protein was distributed in the
      whole bodies of the cells transfected with pEGFP-N1, but mainly distributed on
      the plasma membrane and cytoplasm membrane transfected with GFP-hGPCRc. Thus, the
      localization on the membrane of hGPCRc was accorded with the predication by
      bioinformatic analysis. The expression analysis of hGPCRc by RT-PCR indicated
      that hGPCRc was abundantly expressed in heart, kidney, cerebel and colon etc.,
      but absent in liver, cerebra, small intestine and muscle etc. The expressing
      profile of hGPCRc could provide some useful clues to understanding its effects on
      embryonic development and physiological functions.

PMID- 16108358
TI  - [Recombination and expression of ORF1 and ORF2 gene of porcine circovirus type 2
      and gene of pseudorabies virus].
AB  - ORF1 and ORF2 gene of porcine circovirus type 2 were cloned by PCR with the
      specific primers designed according to genome of PCV2 (AY035820). Following
      extraction and digestion, PCR products were subsequently inserted into universal
      transfer vector plECMV (deleted partial gE and gI of pseudorabies virus) to
      generate recombinant transfer plasmid pIEORF1-ORF2. The genomic DNA of PRV TK-/gE
      /LacZ+ strain and pIEORF1-ORF2 were co-transfected into IBRS-2 cells with
      lipofectin, and recombinant virus TK- /gE- /gI- /ORF1-ORF2+ was selected by PCR
      with ORF1 gene and ORF2 gene primers respectively. The recombinant virus was
      analyzed with Southern blotting and Western blotting. The results indicated that
      ORF1 and ORF2 gene of PCV2 had been inserted into the genome of TK- /gE- /LacZ+
      strain and the expressed ORF1-ORF2 fusion protein could react with PCV2 positive
      sera. Result of virus titers detection showed the insertion of ORF1 and ORF2 gene
      did not influence propagation of recombinant virus.

PMID- 16108359
TI  - [Sequencing and expression analysis of a novel HMW-glutenin gene Kx from
      Crithopsis delileana].
AB  - Using SDS-PAGE analysis, the High-molecular-weight (HMW) glutenin subunits of two
      Crithopsis delileana accessions were detected. It was found that the two
      accessions had the same HMW glutenin subunits. Only one HMW glutenin subunit with
      the similar electrophoresis mobility to the y-type HMW glutenin subunit of
      hexaploid wheat was observed in C. delileana. However, It was indicated that this
      glutenin subunit was an x-type glutenin subunit Kx by gene sequence analysis. The
      full coding region of Kx gene is 2052bp and could encodes a mature protein with
      661 amino acid residues. The Kx gene could be expressed in the bacterial
      expression system, and the expressed protein had the same electrophoresis
      mobility as that in the seed of C. delileana. The primary structure of Kx subunit
      was very similar to the x-type HMW glutenin subunits encoded by the A, B and D
      genomes of wheat, the C and U genomes of Aegilops, and the R genome of Secale
      cereale. In the phylogenetic analysis, Kx subunit was clustered together with Ax1
      subunit by an interior parallelled branch. In conclsion, Kx gene is a novel x
      type glutenin subunit gene from C. delileana.

PMID- 16108360
TI  - [Expression of the soluble human Fas ligand in Dictyostelium discoideum].
AB  - An expression system is described for high-yield production of recombinant
      soluble human FasL (shFasL) in Dictyostelium discoideum cells. DNA encoding amino
      acids 141 - 281 of hFasL was PCR amplified from cDNA derived from activated human
      neutrophils. The resulting product was fused with a DNA fragment encoding hCG
      beta signal peptide and cloned in the expression vector pMB12neo. Dictyostelium
      strain AX3 was transfected with this plasmid, yielding a recombinant strain
      called AX3-pCESFL95-H3. In order to improve the shFasL expression level, pMB12neo
      was optimized by replacing its transcriptional terminator/ polyadenylation
      segment of the 2H3 gene with an actin8 terminator/polyadenylation segment,
      yielding derived expression vector pMB74. The recombinant Dictyostelium strain
      called AX3-pLu8 was generated with this new plasmid. When the recombinant cells
      were cultivated in a complex HL-5C medium, a cell density of (1.5 - 2) x 10(7)/mL
      was reached, and the shFasL level expressed by strains AX3-pCESFL95-H3 and AX3
      pLu8 was 23.5 microg/L and 206 microg/L, respectively. By using a newly developed
      synthetic medium called SIH as culture medium, higher cell density of (4 - 5) x
      10(7)/mL was achieved. Correspondently, 111 microg/L and 420 microg/L shFasL were
      secreted by recombinant strains AX3-pCESFL95-H3 and AX3-pLu8, respectively.

PMID- 16108361
TI  - [Co-expression of gpd1 and hor2 from Saccharomyces cerevisiae in Escherichia
      coli].
AB  - Based on the principle of the pathway engineering, a novel pathway of producing
      glycerol was built in E. coli. The gpd1 gene encoding glycerol 3-phosphate
      dehydrogenase and the hor2 gene encoding glycerol 3-phosphatase were cloned from
      Saccharomyces cerevisiae, respectively. The two genes were inserted into
      expression vector pSE380 together. A recombinant plasmid pSE-gpd1-hor2 containing
      polycistron was constructed under the control of the strong trc promoter. Then it
      was transformed into E. coli BL21. The result showed the recombinant
      microorganism GxB-gh could convert glucose to glycerol directly. And the
      recombinant microorganism GxB-gh was incubated to produce glycerol from D-glucose
      in the fermentor. The maximal concentration of glycerol was 46.67g/L at 26h.
      Conversion rate of glucose was 42.87%. The study is about "green" producing
      glycerol by recombinant microorganism and is also useful for further working in
      recombining microorganism of producing 1,3-propanediol.

PMID- 16108362
TI  - [Cloning and expression of Fusarium moniliforme CGMCC 0536 D-lactonohydrolase
      gene in Escherichia coli].
AB  - The total cDNA obtained through reverse transcription of F. oxysporum CGMCC 0536
      mRNA used as template, a fragment about 1.5kb was amplied with oligo(dT)15 primer
      and a gene specific primer designed on the base of the sequence of both NH2
      terminus and the cDNA sequence encoding D-lactonohydrolase of Fusarium oxysporum
      reported on the NCBI, then the fragment was cloned to the pMD18-T vector and
      sequenced. The sequence encoding D-lactonohydrolase of F. moniliforme CGMCC 0536
      shows a high homology of 90.06% with that of F. oxysporum indicating that the
      gene encoding D-lactonohydrolase is highly conservative. Two specific primers
      were designed according to the sequence result, and a fragment, 1146bp, was
      amplied using hot start PCR with these two specific primers. Subsequently, the
      resulting products were digested with EcoR I and Sal I and ligated to the pTrc99a
      vector digested with the same enzymes using T4 DNA ligase. the recombinant
      plasmid, pTrc99a-LAC, was transformed into Escherichia coli JM109. The two
      positive clones were induced with IPTG, and enzymes expressed in Escherichia coli
      JM109, the enzyme activity was about 37U and 41U respectively. The expression
      products were analyzed by SDS-polyacrylamide gel electrophoresis indicating that
      about 40kD protein was obtained.

PMID- 16108363
TI  - [Flk1+ mesenchymal stem cells ameliorate carbon tetrachloride-induced liver
      fibrosis in mice].
AB  - Fibrosis is the common end stage of most liver diseases. Unfortunately, there is
      no effective treatment available currently. This study was designed to evaluate
      the effect of Flk1+ mesenchymal stem cells (MSC) from murine bone marrow (Flk1 +
      MSC) on fibrosis formation induced by carbon tetrachloride (CCl4). In this study
      Flk1+ MSC were isolated from bone marrow of male BALB/c mice. A CCl4 induced
      hepatic fibrosis model was used. Flk1+ MSC were systemically infused immediately
      or one week after the female mice were challenged with CCl4. Fibrosis index and
      donor cell engraftment were assessed two or five weeks after CCl4 challenge. We
      found that Flk1+ MSC transplantation immediately, but not one week after exposure
      to CCl4, significantly reduced CCl4-induced liver damage and collagen deposition.
      In addition, levels of hepatic hydroxyproline and serum fibrosis markers (HA, P
      III-P) in mice receiving immediate Flk1+ MSC transplantation after CCl4 challenge
      were significantly lower compared to those of control mice. More importantly,
      histological examination suggested that hepatic damage recovery was much better
      in these immediately Flk1+ MSC-treated mice. Immunofluorescence, PCR, and
      fluorescence in situ hybridization (FISH) analysis revealed that donor cells
      engrafted into host liver, had epithelium-like morphology and expressed albumin
      (ALB), although at low frequency. In conclusion Flk1+ MSC might initiate
      endogenous hepatic tissue regeneration, engraft into host liver in response to
      CCl4 injury, and ameliorate its fibrogenic effects.

PMID- 16108364
TI  - [Effects of methyl jasmonate and salicylic acid on phenylethanoid glycosides
      synthesis in suspension cultures of Cistanche deserticola].
AB  - The present study investigated the influence of the methyl jasmonate and
      salicylic acid elicitors on the formation of phenylethanoid glycosides (PeG) in
      the suspension cultures of Cistanche deserticola. The results showed that methyl
      jasmonate and salicylic acid enhanced greatly the accumulation of PeG and
      echinacoside (Echin), but their optimum elicitation dosage and addition time were
      different. The yields of PeG and Echin were significantly increased in the
      presence of 5 micromol/L methyl jasmonate on day 14 (up to 2.59-fold and 3.82
      fold, respectively), whereas treated with 50 micromol/L salicylic acid on day 28,
      the maximum content of them were, respectively, 2.71 and 3.16-fold higher than
      the untreated cell cultures.

PMID- 16108365
TI  - [Identification and mode of action of a xylanase A purified from the culture
      filtrate of Bacillus pumilus WL-11].
AB  - Microbial xylanases have received a great deal of attention in the last two
      decades for their potential applications in food, paper making and animal feed
      industries. Bacillus pumilus WL-11 was identified as a producer of alkane
      xylanase free of cellulase after screening soil samples of paper-making
      factories. The xylanase A (XylA) was purified to homogeneity from the culture
      filtrate of Bacillus pumilus WL-11 by (NH4) 2SO4 precipitation, CM-Sephadex and
      Sephadex G-75 chromatographies. The molecular mass of XylA is estimated to be
      26.0 kD by SDS-PAGE and its isoelectric point is 9.5. The apparent Km is 16.6
      mg/mL and V(max) is 1263 micromol/(min x mg) towards oat spelt xylan. XylA is
      optimally active between pH 7.2 and 8.0, and stable at pH 6.0 to 10.4. The enzyme
      is optimally active at 45 degrees C - 55 degrees C and stable at temperature
      below 45 degrees C, with its half time of activity of 35 min and 15 min at 55
      degrees C and 60 degrees C respectively. HPLC analysis revealed that hydrolysis
      patterns of xylans from oat spelt, birch wood and beech wood by purified XylA
      were different. The XylA is determined to be an endo-beta-1,4-xylanase, as it
      generated mainly xylotriose and no xylose was detected among the three
      hydrolysates. XylA has strong hydrolytic activity towards the pentose in the
      hydrolysates of beech wood and birch wood xylans, but was not active to the
      pentose in the hydrolysate of oat spelt xylan. The crude WL-11 enzyme can
      efficiently hydrolyze oat spelt xylan to a series of xylo-oligosaccharides,
      suggesting its potential application in nutraceutical industry.

PMID- 16108366
TI  - [Hydrophobic interaction between beta-sheet B1 and B2 in xylanase XYNB
      influencing the enzyme thermostability].
AB  - A homology modeling of xylanase XYNB from Streptomyces olivaceoviridis A1 was
      made by Swiss-Model. The hydrophobic Interaction between beta-sheet B1 and B2 in
      the tertiary structure model of XYNB was compared with other thermophilic
      xylanase. A T11Y mutation was introduced in XYNB by site-dirrected mutagenesis to
      improve the thermostability of the enzyme. The XYNB and mutant xylanase (XYNB')
      expressed in Pichia pastoris were purified and their enzymatic properties were
      determined. The result revealed that the thermostability of XYNB' was obviously
      higher than that of XYNB. The optimal temperature of XYNB' for its activity was
      60 degrees C, similar to XYNB. But, compare to XYNB, the optimal pH value, the Km
      value and the specific activity of XYNB' had also been changed. The research
      results suggested that the aromatic interaction between beta-sheet B1 and B2 in
      xylanase should increase enzyme thermostability. The mutant xylanase XYNB' is a
      good material for further research in the relationship between structure and
      function of xylanase.

PMID- 16108367
TI  - [Purification and characterization of a lysozyme from a marine microorganism].
AB  - A novel lysozyme was purified from a marine microorganism and its major
      characteristics were studied. Cell-free supernatant was prepared by
      centrifugation of culture broth, ultrafiltration using a hollow fiber (molecular
      weight cut off, 50kD) and concentration using a hollow fiber (molecular weight
      cut off, 10kD). The crude lysozyme was purified 34.7 fold to electrophoretic
      homogeneity with a recovery of 24.1% by CM-Sepharose FF cationic-exchange and
      Sephadex G-100 gel chromatography. The relative molecular weight of this lysozyme
      was determined as about 39 kD. The optimum pH and temperature towards Micrococcus
      lysodleikticus were pH 8.0 and 35 degrees C respectively, and the enzyme was
      stable at temperature below 50 degrees C and pH 5.0 - 10.0. The lysozyme activity
      was slightly enhanced by Zn2+ and Cu2+ and slightly inhibited by Mn2+ and Ag+.
      The lysozyme showed good compatibility to many common chemical agents such as
      EDTA (0.1%) and KH2 PO4 (1.0%). The lysozyme had broad-spectrum against many
      bacteria, including a number of pathogens, which were resistant to egg-white
      lysozyme.

PMID- 16108368
TI  - [Synthesis of diacylglycerol using immoblized regiospecific lipase in
      continuously operated fixed bed reactors].
AB  - Diacylglycerol, DAG, because of its multifunctional and nutritional properties,
      attracted considerable attention recently. Enzymatic synthesis of diacylglycerols
      from linoleic acid was investigated in a solvent-free reaction in a continuously
      operated fixed bed reactors containing Lipozyme RM IM. By appropriate
      manipulation of the fluid-residence time, the relative proportions of the various
      acylglycerols in the effluent stream can be controlled. In addition, the presence
      of excess glycerol is effective for the removal of water produced during the
      esterification reactions. Under the conditions of molar ratio of linoleic acid to
      glycerol of 0.5, the immoblized enzyme maintained high stability and allowed the
      reaction to continue for 10 days without significant deterioration in enzyme
      activity. It was determined that the conversion of fatty acid, content of 1,3-DAG
      and volume efficiency of reactor reached optima under the conditions: a packaged
      bed reactor(with a ratio of packed length to inner diameter of 7.8), reacting
      temperature at 65 degrees C, molar ratio of linoleic acid to glycerol of 0.5, and
      feeding flow rate of 1.2 mL/min.

PMID- 16108369
TI  - [Studies on fermentation conditions and purification of mutant human interleukin
      2 expressed in Pichia pastoris].
AB  - Interleukin-2 (IL-2) was initially isolated as a T cell growth factor and had
      been shown to direct the expansion and differentiation of several hematopoietic
      cell types. Clinical studies using IL-2 in the treatment of AIDS have been
      encouraging, due to its critical role as a proliferative signal for activated T
      lymphocytes. IL-2 has also undergone trials in the treatment of several types of
      cancer, based on its stimulation of cytotoxic, antitumor cells. Today, human IL-2
      is produced completely by genetically engineered method, and it has been proved
      that genetically engineered recombinant human IL-2 has almost the same function
      and clinical effect as wild IL-2. In the former study, recombinant human IL-2
      usually comes from E. coli, in this paper the mutant IL-2 was successfully
      expressed and purified in Pichia pastoris for the first time. As a eukaryote,
      Pichia pastoris has many of the advantages of higher eukaryotic expression
      systems such as protein processing, protein folding, and posttranslational
      modification, while being as easy to manipulate as E. coli or Saccharomyces
      cerevisiae. It is faster, easier, and less expensive to use than other eukaryotic
      expression systems such as baculovirus or mammalian tissue culture, and generally
      gives higher expression level. Expression conditions of human mutant interleukin
      2(the codon for cysteine-125 of human IL-2 with alanine; the codon for leucine-18
      with methionine; the codon for leucine-19 with serine) in the recombinant Pichia
      pastoris strain were optimized via test of some factors such as the rate of
      aeration, the inductive duration, the initial pH and the concentration of
      methanol. The results from tests showed that the most important parameter for
      efficient expression of interleukin-2 in recombinant Pichia pastoris strain is
      adequate aeration during methanol induction, and the optimum inductive condition
      for interleukin-2 expression was: more than 80% aeration, 2 days for induction,
      the initial pH of 6.0, the final methanol concentration of 1.0%. With this
      condition, the expressed IL-2 was secreted into fermentation broth and reached a
      yield of 30%, approximately 200 mg/L. Expressed interleutin-2 (MvIL-2) was
      isolated and purified by centrifugation, millipore filtration to concentration,
      Econo-PacS strongly acidic cation exchanger cartridge and molecular sieve
      chromatography and the yield of MvIL-2 was 27%. MvIL-2 was purified to
      electrophoretic purity by SDS-PAGE and only one peak being loaded on HPLC.
      Purified MvIL-2 protein had stimulating activity similar to the wild type of IL-2
      as assayed by IL-2-dependent CTLL-2 cells. However, the stability of MvIL-2 was
      superior than that of IL-2 at different temperatures. The activity of obtained
      MvIL-2 was 4 - 5 times of the wild type of IL-2, So MvIL-2 had an advantage over
      wild type of rhIL-2 in storage stability and activity.

PMID- 16108370
TI  - [Comparison of the proteome of the sporutated oocysts of Eimeria tenella
      diclazuril sensitive strain with diclazuril resistant strain].
AB  - Two-dimensional electrophoresis (2-DE) was employed to compare the proteome of
      Diclazuril-resistance Eimeria tenella with that of sensitive strains for
      identifying unique proteins of these stains. 5 protein spots were found to
      express differentially. Four spots which remarkably were measured by matrix
      assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF
      MS). The data obtained from peptide mass fingerprinting were used in NCBInr
      database search, two protein spots in gel were identified as Eimeria tenella
      sporulated oocyst TA4 antigen protein, Heat shock 70kD protein, two protein spots
      were functional proteins of Eukaryote. These proteins are potentially basic work
      for finding molecular mechanism about drug-resistance of Eimeria tenella and new
      marker in the detection of resistance of Eimeria tenella.

PMID- 16108371
TI  - [The periodic change of environment factors in solid state fermentation and
      effect on microorganism fermentation].
AB  - The periodic change of environment factors in air pressure oscillation solid
      state fermentation bioreactor was studied. Based this research the effect of the
      periodic environment stimulations on Penicillium decumbens JUA10 cultured in
      solid state substrate was researched too. The research results showed that in
      this bioreactor air temperature and relative humidity had large amplitude
      periodic change drived by air pressure oscillation. The changes had same
      frequency with the air pressure Oscillation and had amplitude that increased with
      the air pressure increased. When the press lower limit and upper limit were
      0.0MPa and 0.2MPa respectively, pulsating period was 20 min, contrast to the
      period gather breath solid state fermentation, the air press pulsating SSF had a
      2.29 times total CO2 production increase, 3.2 times enzyme activity increase and
      1.04 times biomass increase. The data suggested air press pulsating stimulation
      not only increased biomass but also the metabolic activity.

PMID- 16108372
TI  - [Purification and monosaccharide composition of saponin from Asparagus
      officianlis L].
AB  - The saponins extracted from the stem of Asparagus officinalis L., is a glucoside.
      In the mean time, it solved the problem of environment pollution about wastes of
      Asparagus officinalis L., and made the waste useful. The factors affected
      extractive efficiency of the saponin from Asparagus officinalis L. was
      investigated. The optimal conditions were 95% alcohol; V/W = 6:1; 90 degrees C;
      4h. The saponins average abstraction rate from fresh and dry wastes of Asparagus
      officinalis L. was 1.70% and 4.01% respectively. The saponins were dissociated
      with Al2O3 column. The eluent was 40% alcohol, the elute curves showed a
      symmetrical peak. The compound structure was determined by UV, IR and HPLC
      spectra et al. The results indicated that it belonged to the furostanol saponins
      and its glycosyl composed of xylose, fucose, arabinose, as well as the mole ratio
      was Xyl: Fuc : Ara = 1.0:0.13:19.42, Mw 18 500. In this paper, the saponins were
      extracted from wastes of Asparagus officinalis L. and analyzed glycosyl component
      in detail.

PMID- 16108373
TI  - [Separation of correctly refolded and mis-refolded consensus interferon by
      hydrophobic interaction chromatography].
AB  - Hydrophobic interaction chromatography was used to separate correctly refolded
      and mis-refolded consensus interferon. The effects of ligand types, salt
      concentration, pH and flow rate were investigated. The best result could be
      obtained by using Butyl Sepharose 4 Fast Flow, 0.8 mol/L of ammonium sulfate, pH
      8.3 and 90cm/h of linear flow rate. Reverse-phase HPLC analysis showed the purity
      of the pooled fraction was as high as 99.6%. The specific activity of purified
      consensus interferon was 2.3 x 10(9) IU/mg, The mass recovery of targeth protein
      was 36.7%.

PMID- 16108374
TI  - [Preparation and activity analysis of RGD-mSAK (K130T, K135R)].
AB  - In order to construct RGD-mSAK mutant with reduced immunogenicity, and identify
      its biological activity after purification, mSAK gene fragment was amplified by
      over-lapping extension PCR. Then the gene was inserted into the prokaryotic
      expression vector pBV220 with P(R)P(L) promoters after confirmed by DNA
      sequencing; the expression plasmid pBV220-RGD-mSAK was constructed, and then was
      transformed into E. coli. DH5alpha. After temperature induction, the mutant
      Staphylokinase was over-expressed and much of protein was in the supernate of
      lysate, which is over 50% of total protein in the host. The protein was isolated
      and purified in Q-Sepharose FF, Sephacryl S-200 and SP, high purity protein was
      obtained and its purity was over 98%. The thrombolysis activity of the RGD-mSAK
      protein is 1.68 x 10(5) u/mg by fibrin plate assay, which is slightly higher than
      that of the wild-type, and antiserum titers raised against this protein in guinea
      pigs were much lower than those of wild-type SAK, determined by ELISA. In anti
      platelets aggregation assay in vitro, the RGD-mSAK protein has obvious inhibition
      activity of platelet aggregation in low concentration comparing to the control
      group and wild-type SAK group. So the RGD-mSAK protein is a low immunogenicity,
      bi-function molecular with both thrombolysis activity and anti-embolism activity.
      It provided the basis for further research of RGD-SAK.

PMID- 16108375
TI  - [Extraction and purification of the Klebsiella pneumoniae capsular polysaccharide
      and the effection on the cell immunoactivity].
AB  - Klebsiella pneumoniae was cultured followed by the preparation and immunoactivity
      elucidating of its polysaccharide (CPS). The lysis of cell is the first key step
      in the preparation, under the co-action of trypsin, lysozyme and NP-40, the cell
      lysed within 2h, then the lysate was concentrated by ultrafiltration which serves
      as concentrating and partial purifying action simultaneously. Crude CPS was got
      by ethanol precipitation, then purified through the Ion-exchange and gel
      filtration, the purity of CPS was judged by the gel filtration and agarose gel
      electrophoresis. The effect of CPS on the cell immunoactivity was studied in
      detail, the results show that CPS possesses bidirectional immunoregulation on the
      spleen cells of mice, that is, low concentration of CPS can stimulate the immune
      response while the high concentration manifests the inhibition significantly. The
      investigation results will benefit on the exploitation of the CPS.

PMID- 16108376
TI  - [Simultaneous purification of superoxide dismutase, catalase and hemoglobin from
      bovine erythrocyte lysate with PEG 600 as chaperon].
AB  - Superoxide dismutase, catalase and hemoglobin were purified simultaneously from
      the same batch of bovine erythrocyte lysate. The process involves an initial
      anion exchange chromatography, followed by a hydrophobic interaction
      chromatography and gel filtration chromatography. 0.75% polyethylene glycol 600
      was added as a purification chaperon before the anion exchange chromatography.
      The hemoglobin fraction passed through the ion exchange column without being
      retained. The superoxide dismutase and catalase were adsorbed by the column and
      were eluted separately during elution. The two eluted fractions containing crude
      superboxide dismutase and catalase were further purified with hydrophobic
      interaction chromatography and gel filtration chromatography in sequence. The
      specific activities of superoxide dismutase and catalase were 15932u/mg and
      65918u/mg, respectively. SDS-polyacrylamide gel electrophoresis and gel
      filtration chromatography were used to analyze the purity of the proteins. The
      purity of superoxide dismutase, catalase and hemoglobin were 77.6%, 81.9% and
      99.9%, respectively. The total recoveries for superoxide dismutase, catalase and
      hemoglobin were 47.4%, 29.6% and 88.7%, respectively.

PMID- 16108377
TI  - [Expression and detection of recombinant directing toxin SL120 in Pichia
      pastoris].
AB  - Anti-HIV-1 gp120 single chain antibody(scFv) gene and staphylococcus extoxin
      A(SEA) gene were inserted into vector pPIC9K. The recombinant plasmid was
      integrated into Pichia pastoris by electroporation. High level expression was
      performed by determining the Muts phenotype and screening muti-copy integrants.
      The recombinant protein was about 57kD and the production was 50.1 mg/L. It was
      shown that the two kinds of protein affected the conformation of each other by
      antibody affinity assay, but the recombinant targeting toxins could highly
      mediate CTLs to kill HIV-1 target cells.

PMID- 16108378
TI  - [Cloning and expression of human manganese superoxide dismutase cDNA in Pichia
      pastoris].
AB  - Human manganese superoxide dismutase (hMn-SOD) cDNA was amplified by RT-PCR from
      total RNA of human liver cell (L02), and cloned into yeast expression vector
      pPIC9K containing AOX1 promoter and the alpha-factor signal peptide sequence. The
      resultant pPIC9K-MnSOD was transformed to P. pastoris GS115, screened for Mut+
      carrying multiple copies of hMn-SOD. The positive transformants were fermented in
      flasks and induced by 0.5% methanol. After 4 days of methanol induction, the
      expressed hMn-SOD was up to 32% of the total proteins in the supernatant by SDS
      PAGE with specific activity of 247.7 u/mg.

PMID- 16108379
TI  - [Effect of calcium on aggregation and growth of 293 cells].
AB  - The effect of calcium on the aggregation and growth of 293 cells grown in either
      serum-containing or serum-free medium was investigated in T-flask and spinner
      bottle, respectively. It was found that the concentration of calcium ion, in the
      range of 0.1 mmol/L to 1.0 mmol/L, affected adhesion and aggregation of 293 cells
      severely, but had no distinct effect on growth. The result indicated that the
      attachment of 293 cells was easier with higher calcium concentration in serum
      containing medium. And 293 cells formed aggregates readily in suspension culture.
      This effect was more profound in cultures with higher calcium concentration. The
      average diameter( D, mum) of 293 cell aggregates exhibited direct proportion to
      calcium concentration (c, mmol/L) in serum-free medium. It can be depicted by a
      simple equation in the range of 0.1 mmol/L to 0.5 mmol/L, i.e. D = 58.65c +
      16.96. The aggregation size of 293 cells is regulable in suspension culture,
      therefore, proper control allows for an easier cell retention, and thus a high
      cell concentration potentially can be achieved. However, similar growth of 293
      cells was observed in cultures with different calcium concentration.

PMID- 16108380
TI  - [Construction of mutant population of differential race of Xa23 resistant to rice
      bacterial blight and avirulence activity identification of mutants].
AB  - The mutant population of Xanthomonas oryzae pv oryzae strain differential to rice
      bacterial blight resistance gene Xa23 has been constructed mediated by transposon
      in vivo . The results of PCR amplification with specific primers and analysis of
      flanking sequence of mutants indicated that the foreign DNA has been integrated
      into X. oryzae pv oryzae genome. Four mutants with changed avirulent activity to
      Xa23 gene have been identified by artificial inoculation. It is possible to clone
      genes that are required for AvrXa23 avirulence activity using this new strategy.

PMID- 16108381
TI  - [The study of transformation of tobacco with the stress responsible gene BoRS1
      from Brassica oleracea var. acephala].
AB  - Transgenic tobacco plants expressing a stress responsive gene BoRS1, isolated
      from Brassica oleracea var. acephala, under the control of the 35S promoter of
      the Cauliflower mosaic virus were produced. Some plants were further used to test
      the effect of high level BoRS1 expression on drought stress resistance. The
      presence of transgene in putative transgenic plants was confirmed by PCR
      analysis. Thirty-six among 130 transformants showed amplification of predicted
      fragment of BoRS1 while no amplification was observed in the control. Some
      transgenic lines confirmed by PCR analysis were analyzed through semi
      quantitative one-step RT-PCR for the expression of BoRS1 gene. Amplification of
      1.4 kb cDNA product revealed transcription of BoRS1 gene. Meanwhile, differential
      intensity of the cDNA band indicated variable expression levels of the transgene
      among different transformed lines. The water loss of detached leaves from the
      transgenic plants was slower than that of the control. Transgenic tobaccos and
      the non-transgenic controls were used for further drought stress experiments by
      using different concentration of mannitol. The transformants showed higher
      tolerance to drought stress than non-transgenic plants and different transgenic
      lines exhibited different tolerance during drought stress. These results showed
      that the BoRS1 gene probably play role in enhancing the ability to drought
      stress.

PMID- 16108382
TI  - [Production of functional lipids by lipase-catalyzed acidolysis of lard in
      solvent free system].
AB  - China has richly and inexpensive fat and oils from animal and plants, but these
      resources could not get effectively utilization. In order to make the best of
      these resources, lipase-catalyzed acidolysis of lard with caprylic acid to
      produce functional lipid in solvent free system was investigated. Of the five
      lipases that were tested in the initial screening, immobilized lipase TL IM
      fromca T. languginosa resulted in the highest incorporation of capry lic acid
      into lard. This enzyme was further studied for the effect of enzyme load,
      substrate ratib, reaction time, reaction temperature and added water content on
      the incorporation of caprylic acid into lard. HPLC analyzed the products from the
      acidolysis reaction. The highest incorporation was attained at 20% enzyme load.
      Time course studied suggest that the incorporation of caprylic acid into lard was
      increased up to 38.77 mol% after 24h. Desirable mole ratio of substrates was 1:2
      (lard: caprylic acid), caprylic acid incorporation up to 30.95 mol%. In the range
      of 45 - 60 degrees C , temperature had no significant effect on enzyme activity
      and caprylic acid incorporation changed little. When temperature was above 60
      degrees C, incorporation of caprylic acid into lard was decreased. The highest
      incorporation of caprylic acid into lard 35.76 mol% was attained when added water
      content was 2.5%.

PMID- 16108383
TI  - [Progress in single-domain antibody derived from heavy-chain antibody].
AB  - Functional heavy-chain antibodies (HCAbs) lacking light chains occur naturally in
      camels. The variable domain of heavy chain of heavy-chain antibody is referred to
      VHH. The VHH gene family is homologous to human VH subgroup III. The single
      domain VHH antibodies are constructed by cloning the variable domains of HCAbs.
      Compared to human VHs, VHH germ-line sequences contain some hallmark
      substitutions in framework region 2, including V37F(Y), G44 E, L45 R, W47G. The
      substitutions at positions 44, 45, 47 are often used to camelise the human VHs.
      Being a small binders, VHH antibodies are well expressed, extremely stable and
      very soluble. Camelised human VHs are proved to exhibit the same qualities as
      those of VHH antibodies. The single-domain VHH antibodies will be useful in the
      drug development and basic research.

PMID- 16108384
TI  - [Red/ET recombination and its biomedical applications].
AB  - Red/ET recombination, a powerful homologous recombination system based on the Red
      operon of lambda phage or RecE/ RecT from Rac phage, provides an innovative
      approach for DNA engineering. Deletion, insertion and mutation can be quickly and
      precisely performed on the target gene mediated by Red/ET recombination with PCR
      derived DNA fragments or oligonucleotides. This technical platform has extensive
      applications in biomedical field including bacterial artificial chromosome
      modification, gene knock-out construction and genetic modification of E. coli
      strains as well as some other kinds of microorganisms. Recently, Red/ET
      recombination was improved in several aspects so that it becomes more powerful
      and maneuverable. The characteristic and development of Red/ET recombination and
      its biomedical applications were described in this review.

PMID- 16108385
TI  - [Progress of EBNA1/oriP-based plasmid applied in gene therapy].
AB  - The nonviral gene delivery systems are usually not very effective in transferring
      gene into target cells, and the intensity and duration of the gene expression is
      very poor. The EBNA1/oriP maintain EBNA1/oriP-based plasmids as episome,
      contribute to nuclear transport of the plasmid and transcriptional up-regulation
      of target gene. The EBNA1/oriP based plasmid enhances the transfection rate as
      well as magnitude and longevity of gene expression. This article reviews recent
      preclinical gene therapy studies with the EBV plasmid vectors conducted against
      various diseases. For gene therapy against malignancies, the EBNA1/ oriP based
      plasmid encoding the HSV1-TK suicide gene was combined with a cationic polymer to
      transfer into HCC cell line. The expression level of TK gene was 100- to 1000
      fold higher than the conventional plasmid. The sensitivity of HCC to ganciclovir
      (GCV) elevated several hundred-fold. The EBNA1/oriP based plasmid equipped with
      tumor specific promoter, such as CEA promoter, enabled targeted killing of CEA
      positive tumor cell. Transfection of EBNA1/oriP based plasmid carrying IL-12 and
      IL-18 gene either locally, or systemically, induced therapeufic antitumor immune
      responses including augmentation of the cytotoxic T lymphocyte and natural killer
      activities and growth retardation of tumors. For gene therapy of congenital
      diseases and chronic diseases, the EBNA1/oriP based plasmid encoding the
      adenosine deaminase gene was transfered into human hematopoietic progenitor
      cells. The ADA activity was elevated 1.5-to 2-fold. Intracardiomuscrlar transfer
      of the EBNA1/oriP based plasmid encoding the beta-AR gene may be useful for the
      treatment of severe heart failure. Human tumor necrosis factoralpha (hTNFalpha)
      is one of the most important inflammatory cytokines. It has been implicated in
      many autoimmune and inflammatory diseases. sTNFR can efficiently neutralize the
      bioactivities of hTNFalpha. In primary study we cloned the chimeric protein sTNFR
      II-IgG Fc and expect to use it in the gene therapy of the inflammatory disease
      relative to TNF. In summary, The EBNA1/oriP based plasmid shows advantage in gene
      therapy of cancer, congenital and inflammatory diseases. Moreover, the EBNA1/oriP
      element may greatly contribute to the engineering of a human artificial
      chromosome, the ultimate device for controllable gene therapy.

PMID- 16108386
TI  - Leukocyte immunotherapy improves live delivery rates following embryo transfer in
      women with at least two previous failures: a retrospective review.
AB  - PURPOSE: To determine whether leukocyte immunotherapy (LIT) could improve live
      delivery rate following embryo transfer (ET) in women who were not successful in
      prior attempts. METHODS: Paternal leukocytes were intradermally injected in some
      women who had failed to have a successful pregnancy following at least two prior
      ETs approximately two weeks prior to fresh or frozen ET and repeated at the time
      of the 3rd rising serum beta human chorionic gonadotropin level and at eight
      weeks if a pregnancy occurred. Clinical pregnancy and live pregnancy rates (PRs)
      were compared to those women having ETs during the same time period not receiving
      LIT. RESULTS: Thirty-six of 94 (38.3%) patients receiving LIT (group 1) conceived
      following fresh or frozen ET vs 98 of 341 (28.7%) for women not receiving LIT
      (group 2) (p = NS). The live delivery rate per ET cycle was 30.8% (39/94) vs
      19.7% for group 2 (p = .02). For the subset of women failing despite five
      previous ETs 17 of 37 (45.9%) group 1 women had a clinical pregnancy vs 18 of 64
      (28.1%) group 2 women (p = .07%) and live delivery rates were 35.1% (13/37) vs
      15.6% (10/64) (p = .024). CONCLUSIONS: These retrospective data encourage a
      prospective study of LIT combined with progesterone vs controls receiving
      progesterone only for recalcitrant patients having ETs.

PMID- 16108387
TI  - Preparation for childbirth in different cultures.
AB  - Anthropologically childbirth is an enigma because every woman experiences an
      identical physiological and biological process, wherever the event takes place:
      from a hut in the jungle to a modern hospital in the United States. Differences
      are due to the way that pregnancy, birth and the postnatal period are treated.
      For most women in developing countries, being a woman means being a mother: a
      female is not a woman until she has given birth to a child. Therefore during
      pregnancy she has to follow precise rules and regulations with ritual meanings
      for her protection and that help her get into the role of a mother. Medicine
      offers important technological resources for the prevention, diagnosis and
      treatment of pathology during pregnancy, but with a lack of attention to
      emotional support. Modern society must try to give pregnant women the trust in
      their bodies in order to reach the harmony necessary to give birth "willingly"
      and "with joy".

PMID- 16108388
TI  - A comparison of luteal phase support in graduated estradiol/progesterone
      replacement cycles using intramuscular progesterone alone versus combination with
      vaginal suppositories on outcome following frozen embryo transfer.
AB  - PURPOSE: To compare pregnancy outcome following frozen embryo transfer according
      to type of progesterone (P) support given in the luteal phase. METHODS:
      Retrospective cohort analysis of frozen embryo transfer (ET) cycles in which
      ovulation was suppressed by graduated estradiol in the follicular phase. Two P
      regimens in the luteal phase were compared: P vaginal suppositories and
      intramuscular P vs intramuscular alone. RESULTS: The clinical and viable
      pregnancy rates were significantly higher for the women receiving only
      intramuscular P (57.6% and 43.7%) vs those receiving combined therapy (45.9% and
      35.6%, respectively). The implantation rates were not significantly different
      (22.6% vs 19.5%). CONCLUSION: The increased pregnancy rates with intramuscular P
      may have been related to a higher number of embryos transferred (3.69 vs 3.26).
      Nevertheless, intramuscular P alone is at least as effective, if not more
      effective, than combined therapy for frozen embryo transfers.

PMID- 16108389
TI  - Ectopic pregnancy is not more likely following fresh vs frozen embryo transfer.
AB  - PURPOSE: To determine if the risk of ectopic pregnancy is greater following
      frozen vs fresh embryo transfer (ET). METHODS: Retrospective review of pregnancy
      outcome from January 1, 1997 to November 30, 2003. Cryopreservation was used as a
      simple freezing method and one-step removal of cryoprotectant. The cycles
      consisted mostly of graduated estradiol and progesterone supplementation.
      RESULTS: The ectopic pregnancy rate in 1,445 clinical pregnancies from fresh ET
      was 2.6% vs 2.0% of 975 clinical pregnancies resulting from frozen ET.
      CONCLUSION: In contrast to the conclusions of two previous studies, the present
      study evaluating twice as many clinical pregnancies than the two aforementioned
      studies combined failed to show any greater risk of ectopic pregnancy when
      transfers were performed on day 3.

PMID- 16108390
TI  - Successful pregnancy in a 45-year-old woman with elevated day 3 serum follicle
      stimulating hormone and a short follicular phase.
AB  - PURPOSE: To determine if a successful pregnancy is possible in a woman aged 45
      with elevated day 3 serum follicle stimulating hormone (FSH), a short follicular
      phase, and failure to attain a mature follicle before ovulating. METHODS:
      Ethinyl/estradiol (20 microg daily) was given from day 2 of the menstrual cycle
      until follicular maturation was attained. Progesterone support of 200 mg twice
      daily progesterone vaginal suppositories were given in the luteal phase. RESULTS:
      A mature follicle was attained on day 12 with a serum estradiol of 335 pg/ml.
      Successful pregnancy and delivery were attained. CONCLUSIONS: This is the third
      reported case of a successful pregnancy in a woman > or = 45 years old with
      hypergonadotropism, and the first one reported that was also complicated by a
      short follicular phase.

PMID- 16108391
TI  - A case report to influence therapeutic philosophy when presented with the
      findings on laparoscopy of a unilateral hydrosalpinx with a contralateral
      diseased but patent fallopian tube without hydrosalpinx.
AB  - PURPOSE: To determine if a patent fallopian tube associated with hydrosalpinx can
      be associated with unexplained implantation failure of morphological superior
      embryos. METHODS: Salpingectomy was performed on a woman with a patent fallopian
      tube who had failed to conceive despite the previous transfer of 27 superior
      quality embryos. A single embryo was transferred using minimal stimulation.
      RESULTS: Conception and normal delivery occurred. CONCLUSIONS: A patent tube with
      a hydrosalpinx may be associated with failure of embryos to implant.
      Salpingectomy can correct this defect.

PMID- 16108392
TI  - Placental umbilical cord blood transfusion in transfusion-dependent beta
      thalassemic patients: a preliminary communication.
AB  - The term blood substitute is actually a misnomer because only a part of the total
      functions of the blood is replaced by any available so-called substitute, i.e.,
      oxygen delivery and volume expansion only. Therefore, a more accurate term should
      be red cell substitute. Cord blood, because of its rich mix of fetal and adult
      hemoglobin, high platelet and WBC counts, and a plasma filled with cytokine and
      growth factors, as well as its hypoantigenic nature and altered metabolic
      profile, has all the potential of a real and safe alternative to adult blood
      during emergencies due to any etiology of blood loss and anemia. Our experience
      of 92 units of cord blood transfusion in patients with beta thalassemia with
      severe anemia (hemoglobin concentration varying from 3.5 to 5.9 g/dl with mean
      hemoglobin 4.6 g/dl) proved to be extremely effective in 14 patients as an
      emergency substitute of adult conc RBC transfusion (male: female ratio 1:1, age
      varying from 6 months to 38 years). In the present series, the collection of the
      blood varied from 57 ml-136 ml mean 84 ml +/- 7.2 ml SD, median 87 ml, mean
      packed cell volume 45 +/- 3.1 SD, mean hemoglobin concentration 16.4 g/dl +/- 1.6
      g/dl SD. After collection the blood was immediately preserved in the refrigerator
      and transfused within 72 hours of collection from the consenting mother
      undergoing lower uterine cesarean section. We did not encounter a single case of
      immunological or non immunological reaction. We suggest that the medical
      fraternity use this precious gift of nature, which is free from infection,
      hypoantigenic with an altered metabolic profile, filled with growth factor and
      cytokine filled plasma with potential higher oxygen carrying capacity than for
      adult blood, as an emergency source of blood for the management of transfusion
      dependent beta thalassemics.

PMID- 16108393
TI  - Clinical, ethical, and medical legal considerations on emergency contraception.
AB  - PURPOSE OF INVESTIGATION: To evaluate how many women required the so-called
      "emergency contraception" at our outpatient service and what the actual role is
      of this kind of pharmacological administration in interfering with ovulation and
      pregnancy, paying particular attention to the ethical and medico-legal aspects of
      this subject. METHODS: During the period from 1 December 1998 to 30 November
      2003, emergency contraception was prescribed to a total of 1,160 women. With
      regard to the contraceptives used, in most cases (1,132, 97.6%) a combined oral
      estrogen-progestogen pill (ethinyloestradiol 0.05 mg plus levonorgestrel 0.25 mg)
      was prescribed; in some cases (20 patients, 1.8%) danazol (400 mg), in four women
      (0.3%) a progestin-only pill (levonorgestrel 0.75 mg), and in four other women
      (0.3%) an intrauterine device. RESULTS: It does not come out that there were any
      pregnancies in our study patients since none of them, who were told to come back
      for follow-up, were seen at our termination of pregnancy service or delivery
      room. CONCLUSION: The "Yuzpe regimen" of a combined oral estrogen-progestogen
      pill has been the most commonly used method for emergency contraception. A new
      method recently proposed, a progestin-only pill with levonorgestrel 0.75 mg, is
      having better results than the previous one, with a lower incidence of side
      effects and higher efficacy. Moreover, the treatment with this method does not
      interfere in case of a pregnancy already being carried and cannot interrupt it.

PMID- 16108394
TI  - Local estrogen replacement therapy in postmenopausal atrophic vaginitis: efficacy
      and safety of low dose 17beta-estradiol vaginal tablets.
AB  - PURPOSE OF INVESTIGATION: To verify the effectiveness and safety of low-dose
      17beta-estradiol vaginal tablets in the treatment of the postmenopausal atrophic
      vaginitis. PATIENTS AND METHODS: 325 postmenopausal women with atrophic vaginitis
      in estrogenic replacement therapy with 0.025 mg 17beta-estradiol vaginal tablets,
      one application each day for two weeks, and a single application two times a week
      for the following 22 weeks (total treatment period: 24 weeks). RESULTS: Most of
      the women reported an improvement of symptoms just after two weeks and minimal
      incidence of adverse reactions. No patients showed abnormal endometrial thickness
      and no one had to interrupt the treatment for abnormal uterine bleeding because
      of systemic absorption. CONCLUSION: Low-dose 17beta-estradiol vaginal tablets in
      the treatment of the postmenopausal atrophic vaginitis constitutes an extremely
      valid approach in terms of effectiveness and safety.

PMID- 16108395
TI  - The significance of C-reactive protein in the diagnosis of fetal tachycardia and
      therapy of chorioamnionitis.
AB  - BACKGROUND: [corrected] Pregnant woman with fetal tachycardia have a risk of
      chorioamnionitis as cause of tachycardia. Different studies have supported or
      refuted the use of C-reactive protein (CRP) to diagnose chorioamnionitis. The
      goal of this study was to evaluate serial serum CRP levels for diagnosis of
      chorioamnionitis. METHODS: The study included 60 woman with chorioamnionitis
      confirmed after measuring the levels of CRP. Patients were monitored by CRP
      determination, white blood cell (WBC) count, maternal temperature, maternal and
      fetal heart rate. RESULTS: Elevated CRP level was present in 93.33% of cases.
      Fetal tachycardia was present in 91,67 cases, all associated with elevated CRP
      level. Increased WBC count was present in 63.33%. A statistically significant
      difference was found in the level of CRP in pregnant women with increased WBC
      count compared with those without (p < 0.01). CONCLUSION: Elevated C-reactive
      protein levels were more sensitive than other standard laboratory or clinical
      tests in predicting chorioamnionitis. Also, recent reports indicate that serial
      CRP levels during this interval may be useful for monitoring antibiotic
      treatment.

PMID- 16108396
TI  - The efficacy and tolerability of iron protein succinylate in the treatment of
      iron-deficiency anemia in pregnancy.
AB  - The aim of this study was to evaluate the efficacy and tolerability of iron
      protein succinylate in the treatment of iron-deficiency anemia in pregnancy. One
      hundred and thirty anemic pregnant women were studied. Inclusion criteria were
      iron-deficiency type of anemia, and hemoglobin levels below of 11.5, 10.9 and
      10.3 g/dl for the three trimesters of pregnancy, respectively. Twenty-five women
      who presented pregnancy-related complications were excluded during treatment. The
      remaining 105 were treated with 1600-mg iron protein succinylate per os daily for
      a period of four months. A group of anemia-related clinical signs and symptoms,
      and hematological parameters were recorded at the beginning of treatment, as well
      as two and four months later. They included epidermis and mucosal paleness, skin
      and nail lesions, glossitis, heart pulse, sickness, anorexia, apathy, ataxia,
      polypnea, insomnia, nervousness, paresthesias and other neurological symptoms;
      the hematological parameters included Hgb, hct, RBCs, WBCs, MCV, MCH, MCHC, PLTs,
      serum Fe and ferritin. Possible side or adverse effects were considered during
      treatment. The majority of symptoms and signs of anemia were gradually improved.
      There was a statistically significant increase in the means of Hgb, hct, WBCs,
      MCV, MCH, PLTs and serum ferritin (p < 0.05). Anemia was effectively treated in
      100/105 (95.2%) women, but not in five patients (4.8%) who displayed poor
      compliance to the therapeutic protocol. There were transient and mild side
      effects in seven (6.6%) treated women, namely diarrhea, epigastralgia, vomiting,
      and nausea, which however, did not necessitate discontinuation of the therapeutic
      protocol. Iron protein succinylate is an effective and well tolerated treatment
      of iron-deficiency anemia in pregnancy.

PMID- 16108397
TI  - Fetal and neonatal ovarian cysts: what's their real meaning?
AB  - PURPOSE OF INVESTIGATION: The management of fetal ovarian cysts is still
      controversial despite the improvement in prenatal diagnosis with ultrasonography.
      Some studies suggest an aggressive management, while others opt for a
      conservative one. The prognosis of the majority of congenital ovarian cysts is
      good since they have a benign origin. Sometimes, however, complications such as
      torsion or rupture can occur which often require surgical intervention after
      delivery. In this paper we report our experience and a brief review of the
      literature. METHODS: The authors report on 32 pregnant women in whom
      ultrasonography revealed the presence of an echo-rare or echo-free area in the
      fetal abdomen suggestive of an ovarian cyst. All women were followed-up during
      pregnancy with serial ultrasound examinations. Postnatal ultrasound controls
      confirmed the prenatal diagnosis in all cases. The diameters of the cysts ranged
      from 2.7 to 7.5 cm. RESULTS: In the 16 cases (50%) in which the cyst diameter was
      below 4 cm, periodic ultrasound examinations revealed a tendency towards
      spontaneous regression of the cysts. In the other 16 cases (50%) in which the
      cyst diameter exceeded 4 cm, cystectomy was necessary due to subsequent
      complications (torsion in 6 cases, 37.5%, and intracystic hemorrhage in the other
      10, 62.5%). CONCLUSION: The most appropriate clinical approach in the management
      of benign feto-neonatal ovarian cysts is to adopt a wait-and-see policy,
      assessing the course of the condition by means of periodic ultrasound monitoring.
      Only when tumefactions measure more than 4 cm in diameter with attendant
      complications is surgical therapy indicated. Without complications, however,
      aspiration of the cystic contents is possible even in ovarian cysts exceeding 4
      cm in diameter.

PMID- 16108398
TI  - Epidural anesthesia from an obstetrics point of view.
AB  - With the acceptance of new ideas in medicine and modernization of life styles, it
      is necessary to conduct delivery as a beautiful act of giving life with the least
      amount of pain possible using epidural anesthesia. Thus, not only is the physical
      aspect of delivery improved but also benefits from anesthesia are seen in
      obstetrics. To conduct epidural anesthesia successfully during delivery, certain
      conditions are necessary regarding the fetus and mother. Such conditions include
      an adequate Bishop score, fetal head presentation, the presence of amnion,
      adequate term of delivery and Doppler flows that do not compromise vaginal
      delivery. Primiparas in term pregnancies without pathological conditions related
      to mother or fetus were examined. The duration of delivery was observed in a
      group of primiparas that did not receive epidural anesthesia (group A) and a
      group of primiparas that received epidural anesthesia (group B). The study lasted
      one year.

PMID- 16108400
TI  - Uterine arteriovenous malformation: a case report diagnosed by sonohysterography.
AB  - PURPOSE OF INVESTIGATION: The aim of this report is to describe a case of uterine
      arteriovenous malformation that occurred in a 54-year-old postmenopausal woman
      referring recurrent postmenopausal bleeding, after two years of tamoxifen
      therapy. METHODS: Medical therapy with GnRh agonists was unsuccessful. Ultrasound
      and Doppler flow ultrasound scanning were normal and the following hysteroscopy
      was normal as well. RESULTS: Hysterosonography performed on the patient made us
      suspect the presence of an intracavitary vascular lesion which was confirmed
      histologically after hysterectomy. CONCLUSION: In our case hysterosonography
      allowed us--by creating optimal contrast between the uterine wall and the uterine
      cavity--to suspect and identify the lesion and to recognize the typical
      ultrasound findings of this pathology not visualized with standard transvaginal
      ultrasound.

PMID- 16108399
TI  - Administration of recombinant human erythropoietin in patients with gynecological
      cancer before radical surgery.
AB  - The purpose of this prospective study was to investigate the efficacy of
      preoperative administration of recombinant human erythropoietin in patients with
      gynecological cancer. METHODS: The study included 38 women with gynecological
      cancer who were divided randomly in two groups. Study group A included 20 women
      with gynecological cancer who received recombinant human erythropoietin (rHuEPO)
      plus iron supplementation for ten days before surgery and five days
      postoperatively. Group B (controls) included 18 patients who received only iron
      supplementation for the same time period. Blood samples were obtained on days 
      10, -3, 0, +3, +5, +10. RESULTS: The mean hemoglobin level was significantly
      higher in group A than in group B on the day of the operation and remained
      significantly higher postoperatively while an inverse relationship was observed
      for mean ferritin values in the two groups. CONCLUSION: Preoperative
      administration of rHuEPO in patients with gynecological cancer seems to be
      effective in the blood management of these patients.

PMID- 16108401
TI  - Correlates of age at menopause and osteoporosis in Saudi women.
AB  - OBJECTIVE: To evaluate the age of menopause among Saudi Arabian women and to
      predict the local trend in the prevalence of osteoporosis. MATERIAL & METHOD: All
      menopausal women who had bone mineral density studies at King Khaled University
      Hospital, Riyadh, Saudi Arabia, between 1999 to 2003. Correspondence and logistic
      regression analysis were conducted to identify variables that were positively
      associated with age of menopause. RESULTS: 935 postmenopausal females were
      included. The mean age of menopause was 48.1 +/- 5.9 years. Early and late onset
      of menopause were associated with osteoporosis, while normal onset of menopause
      was associated with osteopenia or remained normal. There was no association
      between age of menopause and parity or body mass index. CONCLUSION: The age of
      menopause among Saudi women is lower than in Western countries but similar to
      other Arabic countries. In addition to cultural differences genetics play a role
      in determining the age of menopause and the development of osteoporosis.

PMID- 16108402
TI  - Grade 3 vulvar and anal intraepithelial neoplasia in a HIV seropositive child-
      therapeutic result: case report.
AB  - A case report of a HIV seropositive 8-year-old child with vulvar and anal border
      neoplasia, both grade 3, and the adopted therapeutic management are presented.
      The mother reported the history of a progressively growing verrucous lesion in
      the vulva since the age of three and a half years. On physical examination a
      pigmented and elevated lesion was observed in the whole vulvar region extending
      to the anal region and intergluteal sulcus. After biopsies and anatomic
      pathological examination, antiretroviral therapy, adequate for age, and topical
      application of podophyllotoxin associated with Thuya officinalis extract was
      started. Three months afterwards vaporization and CO2 laser excision were
      performed in five sequential sessions, thereafter associated with topical
      imiquimod application. After the first two sessions of laser therapy early
      relapses occurred. After four weeks of imiquimod use, already a significant
      improvement of the lesions was observed, making the following laser therapy
      sessions easier. We conclude that antiretroviral therapy associated with
      podophyllotoxin and Thuya was not effective regarding regression of the lesions.
      Laser therapy alone led to early relapses. The local use of imiquimod associated
      with laser was effective in decreasing and controling the lesions.

PMID- 16108403
TI  - Monochorionic-diamniotic twins resulting from the transfer of a single embryo in
      a woman with decreased egg reserve: a case report.
AB  - PURPOSE: To report the first case of identical twins born to a woman with
      decreased oocyte reserve having a single embryo transfer (ET). METHODS: Minimal
      stimulation with gonadotropins (no more than 75 IU/day of human menopausal
      gonadotropins) for a few days followed by oocyte retrieval. RESULTS: The woman,
      aged 37, had seven in vitro fertilization (IVF) cycles with minimal or no
      gonadotropin stimulation. An embryo was formed in four of seven retrieval cycles
      (57.1%). She conceived on her seventh cycle and delivered monochorionic
      diamniotic twins. This pregnancy was achieved with the transfer of six embryos
      over eight cycles (counting a hyperstimulated cycle performed previously in
      another IVF center following traditional controlled ovarian hyperstimulation).
      CONCLUSIONS: This case demonstrates that successful pregnancies are possible with
      single embryo transfers in women with decreased egg reserve including identical
      twins.

PMID- 16108404
TI  - Recurrent congenital hydrocephalus: two case reports and counseling highlights.
AB  - Familial hydrocephalus presents a very considerable morphological and etiological
      heterogenecity. It can be a manifestation of several autosomal dominant or
      recessive syndromes. The non-syndromal forms include autosomal X-linked or
      recessive types and these tend to be recurrent. We report for the first time in
      the literature on two families with recurrent congenital hydrocephalus each for
      the fourth time. The first showed evidence of X-linked recessive form, while the
      second was an autosomal recessive form. The objective of these reports is to
      highlight the need for proper counseling of such families.

PMID- 16108405
TI  - The SLAM emergency flowchart: a new guide for advanced airway practitioners.

PMID- 16108406
TI  - The Doctrine of Corporate Liability.

PMID- 16108407
TI  - Nurse anesthesia students with disabilities: a legal and academic review of
      potential professional standards.
AB  - Establishing suitable and proper program admission criteria that protect both the
      rights of disabled applicants and professional needs to educate competent
      practitioners concern every nurse anesthesia educational program. Disabled
      Americans must be legally protected while ensuring that future nurse anesthetists
      meet expectations for professional competency To balance these demands, academic
      programs must establish criteria that define qualifying standards for practice.
      Such criteria serve the important function of providing notice to prospective
      applicants, as well as to established practitioners, about minimum professional
      competencies and behaviors. This paper, based on a presentation, "Special Needs
      Students--an Attorney's Perspective," to program faculty of the American
      Association of Nurse Anesthetists in Ft Lauderdale, Fla, in February 2005, posits
      specific language to aid in defining admission criteria that are both inclusive
      and exclusionary. It seeks to stimulate debate about developing some professional
      consensus on a matter of continuing importance.

PMID- 16108408
TI  - Haloperidol: an alternative butyrophenone for nausea and vomiting prophylaxis in
      anesthesia.
AB  - Droperidol has been an efficacious, inexpensive butyrophenone used since the
      early 1970s to prevent or treat postoperative nausea and vomiting. Because of
      reports of sudden cardiac death in patients receiving droperidol, the US Food and
      Drug Administration (FDA) recently placed significant restrictions on its
      administration. These restrictions have essentially removed droperidol from use.
      Haloperidol is another butyrophenone with antiemetic properties but without the
      FDA restrictions. This article reviews the literature regarding haloperidol and
      supports its use as a safe substitute for droperidol in the prevention and
      treatment of postoperative nausea and vomiting.

PMID- 16108409
TI  - Pressure-support ventilation and diaphragm shortening in the rat model.
AB  - Little is known about how pressure-support ventilation affects diaphragm
      performance because there is no direct measurement of diaphragm function in the
      clinical setting. An indicator of diaphragm performance or work is the product of
      diaphragm muscle shortening and intrathoracic pressure during inspiration. We
      studied the effect of pressure-support ventilation on diaphragm shortening,
      diaphragm work, and other cardiopulmonary parameters. In 15 anesthetized Sprague
      Dawley male rats, pressure support was increased from 0 to 10 cm H2O in 2 cm
      increments. Increasing pressure support from 0 to 10 cm H2O resulted in
      respiratory rate decreasing 25%, tidal volume increasing 148%, minute ventilation
      increasing 91%, end-tidal carbon dioxide decreasing 5%, and cardiac output
      decreasing 30%. Progressively increasing pressure support to 10 cm H2O was
      accompanied by decreases in the end-inspiratory pressure without significant
      increases in diaphragm shortening. Therefore, diaphragm work was decreased. The
      lack of an increase in diaphragm shortening in the presence of an increase in
      tidal volume indicated that there was an augmentation of thoracic volume in the
      coronal and/or horizontal axes instead of the cephalocaudal axes throughout
      inspiration. These findings may be useful to nurse anesthetists in the
      understanding of diaphragm work when patients are being ventilated with pressure
      support ventilation.

PMID- 16108410
TI  - Cardiac arrest under anesthesia in a pediatric patient with Williams syndrome: a
      case report.
AB  - Serial cardiac arrests occurred during the induction of a 3-year-old boy for
      elective 1-sided orchiopexy surgery and evaluation under anesthesia of previously
      placed ear tympanoplasty tubes. The child's history included Williams syndrome
      along with hypercalcemia and mild supravalvular aortic stenosis. The initial
      arrests included significant ST wave changes along with profound brodycardia,
      hypotension, and pulseless electrical activity requiring full resuscitation
      twice. The patient was transferred on an emergency basis to the intensive care
      unit (the surgery was cancelled), and a heart catheterization was scheduled for
      the following morning. The patient experienced several cardiac arrests during the
      cardiac catheterization procedure, necessitating emergency extracorporeal
      membrane oxygenation cannulation and immediate transfer to the operating room for
      emergency cardiac surgery. A thorough preoperative cardiac workup, including
      cardiac catheterization, electrocardiogram, and echocardiogram, may decrease
      mortality and morbidity in patients with Williams syndrome. However, cardiac
      catheterization has been associated with increased risk in this patient
      population.

PMID- 16108411
TI  - Neuroprotective effects of thiopental, propofol, and etomidate.
AB  - In selecting an anesthetic agent to be used for neurosurgical procedures, the
      anesthesia provider must consider the agent's effects on intracranial pressure
      (ICP), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen
      consumption (CMRO2). The anesthetic of choice for neurosurgical procedures for
      many decades has been thiopental. It meets the strict requirements for
      neurosurgical procedures because it protects the brain from ischemia and
      herniation by lowering ICP through decreases in CBF and CMRO However, new drugs,
      including etomidate and propofol, have been introduced that offer anesthesia
      providers comparable neuroprotective actions plus other positive attributes. The
      purpose of this course is to review current and benchmark literature on
      thiopental, propofol, and etomidate to compare researchers' reports of the
      effects on ICP, CMRO2, and CBF Literature was gathered using computer assistance
      to search PubMed, the Cumulative Index of Nursing and Allied Health Literature,
      and the World Wide Web. The literature showed that all 3 anesthetic agents
      provide favorable neurological protection. Each drug has some undesirable side
      effects. Knowledge of these side effects and the patient's medical and surgical
      history can help CRNAs determine the most suitable anesthetic in specific
      situations.

PMID- 16108412
TI  - [Selection from 20-th century Hungarian dental literature. Part II. 1901-1945].
AB  - In the first half of the 20th century Hungarian scientific literature accurately
      reflects the beginning of enormous developments in the field of contemporary
      stomatology. Members of the University Clinic, led by Professor Joseph Szabo, as
      well his former students, were the leading authors of scientific publications and
      textbooks. The specialization within the field of stomatology and its division
      into independent minor fields can be observed in the literature, too, mainly from
      the 1920-ies.

PMID- 16108413
TI  - [Caries and periodontal state of pregnant women. Part II. Periodontal state].
AB  - A great number of clinical studies focused on the periodontal health of the
      pregnant women in the last decades, since an association has been presumed
      between the pregnant women's periodontal disease and the adverse pregnancy
      outcome. Altogether 161 healthy women were examined soon after delivery in
      Szeged/Hungary. The periodontal status of the patients was recorded by the
      Silness-Loe Plaque index (0.67), frequency of calculus (21.07%), mean probing
      pocket depth (1.67 mm) and the frequency of bleeding on probing (37.8%). A
      significant correlation was found between the state of the periodontium and the
      educational level and the pregnant women's profession. The periodontal state of
      women with higher education and the intellectuals was much better, than of the
      less educated patients and the manual workers.

PMID- 16108414
TI  - [The use of aminopenicillin combined with a beta-lactamase inhibitor in
      outpatients of oral surgery and dentistry].
AB  - On the basis of the information gained from the literature the
      amoxicillin/clavulanic acid combination has attained the leading position in
      dentistry and outpatient oral surgery practices as regards the order of
      application of antibiotics. The explanation for this may be that in 60-70% of the
      cases of odontogenic inflammation, besides the pathogenic anaerobic bacteria
      there is an increasing necessity to eliminate beta-lactamase-producing bacteria
      as well. The authors applied the amoxicillin/clavulanic acid combination (Aktil
      Duo 625 mg) to support the--primarily surgical--treatment of 14 oral and dental
      surgery conditions on a total of 60 patients. After analysing the results and
      side effects they came to the conclusion that the application of the mentioned
      combination was very successful in dentistry and outpatient oral surgery
      practices.

PMID- 16108415
TI  - [Psychology and psychosomatics of the orthodontic treatment].
AB  - Psychosomatic problems related to orthodontic treatment are a special group of
      oral psychosomatic disorders. The most frequent complaints are related to
      aesthetics and occlusion. Most of the patients are children, adolescence or young
      adults, with special emotional problems. Authors reviewed the most important
      knowledge related to this specific field, but some general aspects of oral
      psychosomatics are also discussed.

PMID- 16108416
TI  - [In vitro comparison of root canal preparation with step-back technique and GT
      rotary file--a nickel-titanium engine driven rotary instrument system].
AB  - The aim of the authors' study was to compare the remaining root canal wall
      thickness and the preparation time of root canals, prepared either with step-back
      technique, or with GT Rotary File, an engine driven nickel-titanium rotary
      instrument system. Twenty extracted molars were decoronated. Teeth were divided
      in two groups. In Group 1 root canals were prepared with step-back technique. In
      Group 2 GT Rotary File System was utilized. Preoperative vestibulo-oral X-ray
      pictures were taken from all teeth with radiovisiograph (RVG). The final
      preparations at the mesiobuccal canals (MB) were performed with size #30 and
      palatinal/distal canals with size #40 instruments. Postoperative RVG pictures
      were taken ensuring the preoperative positioning. The working time was measured
      in seconds during each preparation. The authors also assessed the remaining root
      canal wall thickness at 3, 6 and 9 mm from the radiological apex, comparing the
      width of the canal walls of the vestibulo-oral projections on pre- and
      postoperative RVG pictures both mesially and buccally. The ratios of the residual
      and preoperative root canal wall thickness were calculated and compared. The
      largest difference was found at the MB canals of the coronal and middle third
      level of the root, measured on the distal canal wall. The ratio of the remaining
      dentin wall thickness at the coronal and the middle level in the case of step
      back preparation was 0.605 and 0.754, and 0.824 and 0.895 in the cases of GT
      files respectively. The preparation time needed for GT Rotary File System was
      altogether 68.7% (MB) and 52.5% (D/P canals) of corresponding step-back
      preparation times. The use of GT Rotary File with comparison of standard step
      back method resulted in a shortened preparation time and excessive damage of the
      coronal part of the root canal could be avoided.

PMID- 16108417
TI  - The emerging role of darbepoetin alfa in the management of patients with cancer.

PMID- 16108418
TI  - Improving the management of chemotherapy-induced neutropenia.

PMID- 16108419
TI  - The challenges of oral mucositis and its therapy.

PMID- 16108420
TI  - Nano-devitrification of glassy alloys.
AB  - This overview paper summarizes a large number of data connected with nano
      devitrification of metallic glassy and amorphous alloys on heating which form
      nanoscale crystalline or quasicrystalline particles. In some alloys this effect
      leads to formation of the nanocomposites with enhanced mechanical properties
      compared to fully glassy and crystalline alloys.

PMID- 16108421
TI  - Nanophononics: phonon engineering in nanostructures and nanodevices.
AB  - Phonons, i.e., quanta of lattice vibrations, manifest themselves practically in
      all electrical, thermal and optical phenomena in semiconductors and other
      material systems. Reduction of the size of electronic devices below the acoustic
      phonon mean free path creates a new situation for phonon propagation and
      interaction. From one side, it complicates heat removal from the downscaled
      devices. From the other side, it opens up an exciting opportunity for engineering
      phonon spectrum in nanostructured materials and achieving enhanced operation of
      nanodevices. This paper reviews the development of the phonon engineering concept
      and discusses its device applications. The review focuses on methods of tuning
      the phonon spectrum in acoustically mismatched nano- and heterostructures in
      order to change the phonon thermal conductivity and electron mobility. New
      approaches for the electron-phonon scattering rates suppression, formation of the
      phonon stopbands and phonon focusing are also discussed. The last section
      addresses the phonon engineering issues in biological and hybrid bio-inorganic
      nanostructures.

PMID- 16108422
TI  - Raman studies of new carbon nanotube sample types.
AB  - Generation of new carbon nanotube sample types, including individualized
      nanotubes suspended in surfactant solutions and recently synthesized ultralong
      nanotubes, has enabled new experimental studies that provide useful insight into
      nanotube structure and photophysical behavior. We present a review of Raman
      studies performed in our laboratory on these newly available sample types.
      Results from Raman excitation profile studies of individualized HiPco-produced
      nanotubes have confirmed fluorescence-based chirality assignments and have
      revealed chiral-dependences in the Raman scattering cross-sections. These studies
      have also enabled a direct evaluation of the effects of nanotube bundling on
      electronic and vibrational structure. Confocal Raman imaging is demonstrated as a
      useful technique for probing vibrational structure of ultralong nanotubes over
      large length scales and has resulted in the detection and imaging of a
      semiconductor-to-metallic nanotube intramolecular junction.

PMID- 16108423
TI  - A model for nucleation and growth of single wall carbon nanotubes via the HiPcO
      process: a catalyst concentration study.
AB  - Using the High Pressure carbon monoxide (HiPco) reactor we conducted an
      experiment on the effects of changing the catalyst concentration. With each
      catalyst concentration tested the resulting raw HiPco material was characterized
      for average SWNT lengths, SWNT diameters, residual iron particle size, and large
      fullerene content. We were able to determine trends in each of these
      characteristics as the catalyst concentration was changed. As the catalyst
      concentration was decreased SWNT lengths increased, SWNT diameters increased, the
      residual iron particle size increased, and the large fullerene content decreased.
      From these trends we have developed a Competitive Growth model for nucleation and
      growth of SWNTs via the HiPco process.

PMID- 16108424
TI  - Optical pH response of DNA wrapped HiPco carbon nanotubes.
AB  - Solubilization of single-walled carbon nanotubes in aqueous solution by surface
      functionalization is of great interest for biosensor applications and separation
      of individual nanotubes. Here we have observed that HiPco nanotubes can be stably
      dispersed into double-stranded DNA aqueous solutions. Interestingly, the first
      optical interband transitions of the DNA wrapped semiconducting HiPco nanotubes
      possess a unique pH dependence, a phenomenon observed in SDS-encased and
      carboxylic group functionalized single-walled carbon nanotubes. The unique
      optical pH dependence of surface modified semiconducting nanotubes may have
      promising applications in optical biosensors.

PMID- 16108425
TI  - Electrophoretic and dynamic light scattering in evaluating dispersion and size
      distribution of single-walled carbon nanotubes.
AB  - We have introduced both electrophoretic and dynamic light scattering to evaluate
      the polydispersity, nanodispersity, and stability of single-walled carbon
      nanotubes (SWNTs) in distilled water with surfactants. By controlling the sodium
      dodecyl sulfate composition and some pretreatment by sonication, we were able to
      achieve nanodispersion (dispersion into individual nanotubes). The polydispersity
      was well described by combining both methods. We further showed that the
      nanodispersion and length distribution observed in the dynamic light scattering
      spectra were clearly identified by atomic force microscopy. Although surfactants
      with aliphatic groups can nanodisperse SWNT bundles, the dispersivity and
      stability depended seriously on the sample preparation process. Our measurements
      showed that a combination of electrophoretic and dynamic light scattering can
      provide a convenient and robust means of measuring polydispersity,
      nanodispersity, and stability of SWNTs in various solutions.

PMID- 16108426
TI  - Poly(ethylene-co-vinyl alcohol) functionalized single-walled carbon nanotubes and
      related nanocomposites.
AB  - Single-walled carbon nanotubes (SWNTs) were functionalized by poly(ethylene-co
      vinyl alcohol) (EVOH) copolymer under carbodiimide-activated esterification
      reaction conditions. Similar to the parent EVOH copolymer, the EVOH
      functionalized carbon nanotubes are soluble in highly polar solvent systems such
      as DMSO and hot ethanol-water mixtures. The soluble EVOH-SWNT sample was
      characterized by various techniques, including optical absorption, Raman, NMR,
      electron microscopy, and thermogravimetric analysis. The common solubility of
      EVOH and EVOH-SWNT allowed their intimate mixing in solution, and thus the
      fabrication of nanocomposites in which the SWNTs are homogeneously dispersed in
      the polymer matrix.

PMID- 16108427
TI  - Nanodispersion of single-walled carbon nanotubes using dichloroethane.
AB  - In this paper we present a simple approach of nanodispersing single-walled carbon
      nanotubes (SWCNTs) in a non-polar 1,2-dichloroethane (DCE) solvent. After
      filtration with isopropanol and acetone, the purified SWCNTs were immersed in
      DCE, followed by sonication for about 15 hours. The samples were further
      centrifuged at 17,000 revolutions per minute for about 3 hours. Atomic force
      microscopy (AFM) demonstrated that the spin-coated nanotubes were mostly
      individual nanotubes with an average diameter of 1.6 nm and a length of about 250
      nm. We also found that the presence of water, and the dry process during DCE
      treatment, prevented nanotubes from being nanodispersed.

PMID- 16108428
TI  - A renewable electrochemical magnetic immunosensor based on gold nanoparticle
      labels.
AB  - A particle-based renewable electrochemical magnetic immunosensor was developed by
      using magnetic beads and gold nanoparticle labels. Anti-IgG antibody-modified
      magnetic beads were attached to a renewable carbon paste transducer surface by
      magnet that was fixed inside the sensor. Gold nanoparticle labels were capsulated
      to the surface of magnetic beads by sandwich immunoassay. Highly sensitive
      electrochemical stripping analysis offers a simple and fast method to quantify
      the capatured gold nanoparticle tracers and avoid the use of an enzyme label and
      substrate. The stripping signal of gold nanoparticles is related to the
      concentration of target IgG in the sample solution. A transmission electron
      microscopy image shows that the gold nanoparticles were successfully capsulated
      to the surface of magnetic beads through sandwich immunoreaction events. The
      parameters of immunoassay, including the loading of magnetic beads, the amount of
      gold nanoparticle conjugate, and the immunoreaction time, were optimized. The
      detection limit of 0.02 microg ml(-1) of IgG was obtained under optimum
      experimental conditions. Such particle-based electrochemical magnetic
      immunosensors could be readily used for simultaneous parallel detection of
      multiple proteins by using multiple inorganic metal nanoparticle tracers and are
      expected to open new opportunities for disease diagnostics and biosecurity.

PMID- 16108429
TI  - Preparation of dendrimer SAM on Au substrate and adsorption/desorption of poly-L
      glutamate on the SAM.
AB  - A self-assembled monolayer (SAM) of a dendrimer has been fabricated by covalent
      bonding of amine-terminated dendrimers to 3-mercaptopropionic acid SAM on an Au
      substrate, where an amide bond was formed between the amine and the carboxylic
      acid using amide-coupling reagents. Each reaction step was inspected by
      transmission surface-enhanced infrared absorption spectroscopy. Reaction was
      affected by solvents of the coupling reagents and concentrations of the coupling
      reagents and dendrimers. The pH-dependent adsorption/desorption behavior of
      sodium poly-L-glutamate (PGA) has been examined on the dendrimer SAM prepared.
      The adsorbed amount was abundant at acid pH below the pK(a) of carboxylate, while
      desorption from PGA-adsorbed dendrimer SAM prepared at acid pH proceeded as the
      pH was raised. The reaction was reversible and reproducible within 30 min under
      controlled pH, although the carboxylic acid species adsorbed at pH 4.2 was
      deprotonated to a carboxylate species after more than 30 min of desorption at pH
      9.4.

PMID- 16108430
TI  - Nanocrystalline metal/carbon composites produced by supersonic cluster beam
      deposition.
AB  - In this work we show that supersonic cluster beam deposition is a viable method
      for the synthesis of nanocrystalline metal/carbon composites. By assembling
      carbon and metallic clusters seeded in a supersonic beam, we have grown films
      consisting of metal nanoparticles embedded in a nano-structured carbon matrix.
      Samples containing 3d transition metals (Ti, Ni) and noble metals (Au, Pd, Pt)
      with different metal abundances, particle size and dilution have been
      characterized by transmission electron microscopy. The influence of different
      metals on the structure of the carbon matrix has been investigated. Spatially
      resolved ultraviolet photoemission electron spectroscopy showed substantial
      surface oxidation of 3d transition metal clusters. On a micrometric scale, the
      spatial distribution of the metallic nanoparticles appeared to be homogeneous.

PMID- 16108432
TI  - ZnO nanowires hydrothermally grown on PET polymer substrates and their
      characteristics.
AB  - Zinc oxide nanowires (ZnO NWs) were successfully synthesized on the ITO/PET
      polymer substrates by a hydrothermal method. X-ray diffraction, scanning electron
      microscopy, and transmission electron microscopy investigations were carried out
      to characterize the crystallinity, surface morphologies, and orientations of
      these NWs, respectively. The influence of NW surface morphologies on the optical
      and electrical properties of ZnO NWs was studied. The hydrothermally grown ZnO
      NWs with direct band gap of 3.21 eV emitted ultraviolet photoluminescence of 406
      nm at room temperature. Field emission measurements revealed that the threshold
      electric fields (Eth, current density of 1 mA/cm2) of ZnO NWs/ITO/PET and ZnO
      NWs/ZnO/ITO/PET are 1.6 and 2.2 V/microm with the enhancement factors, beta
      values, of 3275 and 4502, respectively. Furthermore, the field emission
      performance of ZnO NWs deposited on the ITO/PET substrate can be enhanced by
      illumination with Eth of 1.3 V/microm and displays a maximum emission current
      density of 18 mA/cm2. The ZnO NWs successfully grown on polymer substrate with
      high transmittance, low threshold electric field, and high emission current
      density may be applied to a flexible field emission display in the future.

PMID- 16108431
TI  - Layer-by-Layer assembly of TiO2 nanoparticles for stable hydrophilic
      biocompatible coatings.
AB  - Stable, super-hydrophilic (water contact angle approximately equal to 0 degrees)
      titanium dioxide nanoparticle thin films have been obtained on substrates with
      different initial wettability such as glass, poly(methyl methacrylate) and
      poly(dimethyl siloxane) using layer-by-layer nano-assembly method. Titanium
      dioxide nanoparticles were alternated with poly(styrene sulfonate) to form films
      of thickness ranging from 11 nm to 220 nm. The hydrophilicity of these thin films
      increases with increasing number of deposited PSS/TiO2 bilayers. It was found
      that 2, 5 and 20 layers were needed to form super-hydrophilic TiO2 coating on
      glass, PMMA and PDMS respectively. Oxygen plasma treatment of substrate surfaces
      enhanced the formation of homogeneous TiO2 films and accelerated the formation of
      hydrophilic layers. Super-hydrophilicity has been shown to be unique to PSS/TiO2
      films as compared with other polyelectrolyte/nanoparticle layers, and UV
      irradiation may restore hydrophilicity even after months of storing of the
      samples. Biocompatibility of TiO2 nanoparticle films has been demonstrated by the
      successful cell culture of human dermal fibroblast.

PMID- 16108433
TI  - Phase transfer identification of core-shell structures in Ag-Au bimetallic
      nanoparticles.
AB  - The difference between the transfer of poly(vinylpyrrolidone)-protected Au and Ag
      nanoparticles from an aqueous solution to toluene was used to develop a simple
      experimental procedure that can positively identify the formation of bimetallic
      Ag-Au nanoparticles with the core-shell structure. The method was validated by UV
      visible spectroscopy, EDX, and TEM measurements. Using this technique, we have
      found that core-shell nanoparticles of Ag-Au were formed by the seed-mediated
      growth method using Ag nanoparticles as the seeds. The reversed order of using Au
      nanoparticles as the seeds, on the contrary, could only produce a physical
      mixture of Ag-Au core-shell nanoparticles and isolated Ag nanoparticles.

PMID- 16108434
TI  - TEM/AFM investigation of size and surface properties of nanocrystalline ceria.
AB  - A series of ceria nanoparticles were synthesized by using a microemulsion method.
      The effect of relative concentration of surfactant/water on the size and the
      surface roughness of ceria nanoparticles was examined using transmission electron
      microscopy (TEM) and atomic force microscopy (AFM) respectively. The
      investigation confirmed a relationship between the size and the roughness
      properties of the nanoceria as a function of the water to surfactant ratio. With
      increasing dilution of the surfactant, the size distribution became narrow such
      that average particle size decreased linearly as the ratio increased without
      affecting lower size threshold of particles (approximately 10 nm). The surface
      roughness, on the other hand was found to increase with increasing water to
      surfactant ratio implying diluted surfactant would provide rougher surface of
      ceria nanoparticles. The information can be used to tailor the adhesion
      properties of nanoceria by optimizing the size distribution as well as surface
      roughness as a function of water to surfactant ratio.

PMID- 16108435
TI  - Characterization of a novel 1,3-bis(p-iminobenzoic acid)indane Langmuir-Blodgett
      film for organic vapor sensing.
AB  - In the present paper we report about the Langmuir-Blodgett thin film
      characterization and organic vapor sensing properties of a novel 1,3-bis(p
      iminobenzoic acid)indane (IBI) containing polar carboxylic acid groups. LB film
      properties of IBI material is characterized by UV-visible spectroscopy, atomic
      force microscopy, and quartz crystal microbalance. Our results show that high
      quality and uniform LB films can be prepared with the transfer ratio of over
      0.95. Organic vapor sensing properties are studied using quartz crystal
      microbalance measurement system. IBI film is found to be significantly more
      sensitive to benzene and the response of LB sample is fast, large, and
      reversible. The sensitivity of detection of toluene, ethyl alcohol, and isopropyl
      alcohol is much smaller than that of benzene. This newly synthesized IBI is a
      suitable molecule for the fabrication of an LB film and can be regarded as a
      promising sensing material in the development of a room temperature gas sensor
      for benzene vapor applications.

PMID- 16108436
TI  - Deposition feature of Ni nanoparticles on halloysite template and magnetic
      properties of the composite.
AB  - A novel cermet composite with Ni nanoparticles deposited on a hollow cylindrical
      halloysite template is fabricated by electroless plating. Ni nanoparticles have a
      uniform distribution on the template, and their average diameter is mainly in the
      range of 20-30 nm. The halloysite template will be beneficial to make the Ni
      nanoparticles achieve high stability and well-dispersed state. Different heat
      treatment temperatures have a great effect on the crystal structure of Ni
      nanoparticles and the magnetic properties of the composite. With the heat-treated
      temperature increase, Ni nanoparticles gradually become crystallized, and the
      composite values of inherent coercive force (iHc), saturated magnetization (Ms),
      and residual magnetization (Mr) increase respectively. After complete
      crystallization of Ni nanoparticles at 673 K, the composite has the maximum
      values of iHc (253.6 Oe), Ms (57.37 emu/g), and Mr (21.64 emu/g). The sum
      contribution of the magneto-crystalline anisotropy, single magnetic domain
      effect, and the pinning effect of multiple-twinned planar defects in Ni
      nanoparticles would result in the high value of iHc. The new nanosized cermet
      composite will be at such an advantage for its practicable fabrication method,
      higher coercive force, high stability, and low cost that it would have great
      potential to be utilized to design and prepare magnetic materials.

PMID- 16108437
TI  - Vapor phase growth of ZnO nanorod-nanobelt junction arrays.
AB  - By thermally evaporating a mixture of ZnO, SnO2, and graphite powders at 920
      degrees C, large quantities of ZnO nanorods with typical diameters of 20-30 nm
      are grown secondarily from the surfaces of the ZnO nanobelts to form a nanorod
      nanobelt junction array with interesting structural characteristics. A possible
      growth mechanism of the ZnO nanorod-nanobelt junction arrays with high surface-to
      volume ratio is discussed. The ZnO nanorod-nanobelt junction arrays appear an
      enhanced visible emission due to the high quantity of the surface defects related
      to oxygen vacancies. The results reported in this paper would lead to new
      approaches to control the surface structures of ZnO nanomaterials that are
      critical for their applications, such as chemical sensors.

PMID- 16108438
TI  - ZnO nanowires by pulsed laser vaporization: synthesis and properties.
AB  - We report a new pulsed-laser vaporization (PLV) technique to synthesize nanowires
      of single-crystal ZnO having a wurtzite structure by using colloidal gold
      nanoparticles as seeding catalysts. The average diameter of the nanowires is
      approximately 13 nm, with a very narrow range of 7 to 25 nm. The nanowires are
      straight for the most part, with the axes parallel to the [0001] growth
      direction. Raman and photoluminescence spectra from the nanowires and bulk ZnO
      are similar except for a approximately 510 nm band in the nanowires due to oxygen
      vacancies. The bulk-like vibrational and electronic properties of the nanowires
      is due to the diameter being larger than the threshold below which quantum
      confinement-induced effects are expected.

PMID- 16108439
TI  - Optical studies on chemical bath deposited nanocrystalline CdS thin films.
AB  - Nanocrystalline cadmium sulphide thin films were prepared by the chemical bath
      (CB) deposition using a mixed aqueous solution of cadmium chloride, thiourea, and
      ammonium chloride. The XRD patterns showed that the CdS films were of hexagonal
      phase with preferred (002) orientation. From ellipsometric measurements, the film
      thickness was found to be in order of 66 nm and the optical band gap was
      estimated to be 2.4 eV.

PMID- 16108440
TI  - Enhancement of ionic conductivity of PEO based polymer electrolyte by the
      addition of nanosize ceramic powders.
AB  - The ionic conductivity of polyethylene oxide (PEO) based solid polymer
      electrolytes (SPEs) has been improved by the addition of nanosize ceramic powders
      (TiO2 and AL2O3). The PEO based solid polymer electrolytes were prepared by the
      solution-casting method. Electrochemical measurement shows that the 10 wt% TiO2
      PEO-LiClO4 polymer electrolyte has the best ionic conductivity (about 10(-4) S
      cm(-1) at 40-60 degrees C). The lithium transference number of the 10 wt% TiO2
      PEO-LiClO4 polymer electrolyte was measured to be 0.47, which is much higher than
      that of bare PEO polymer electrolyte. Ac impedance testing shows that the
      interface resistance of ceramic-added PEO polymer electrolyte is stable. Linear
      sweep voltammetry measurement shows that the PEO polymer electrolytes are
      electrochemically stable in the voltage range of 2.0-5.0 V versus a Li/Li+
      reference electrode.

PMID- 16108441
TI  - Peptide-assisted synthesis of gold nanoparticles and their self-assembly.
AB  - A novel gold nanoparticle-tripeptide (GNP-tripeptide) conjugate was prepared by
      peptide in-situ redox technique at ambient temperatureusing a newly designed
      tripeptide. This new tripeptide was nso designed that it has a C-terminus
      tyrosine residue, which reduced Au+3 to Au, and the terminally located free amino
      group was bound to the gold nanoparticle (GNP) surface resulting in highly stable
      Au colloids. The average diameter of the tripeptide-stabilized GNP is 8.7 +/- 2.3
      nm. Tripeptide bound gold nanoparticles formed three-dimensional assemblies in
      the presence of an excess of similar or disimilar tripeptides. The aggregation of
      GNPs results in a red shift in the surface plasmon resonance from lambda max =
      527 to 556 nm. The effect of the solvent, concentration, and nature of the
      tripeptides on the assembly process were investigated by TEM and UV-visible
      spectroscopy.

PMID- 16108442
TI  - Effect of heterocyclic based organoclays on the properties of polyimide-clay
      nanocomposites.
AB  - Polyimide-clay nanocomposites were prepared from their precursor, namely,
      polyamic acid, by the solution-casting method. Organomodified montmorillonite
      (MMT) clay was prepared by treating Na+MMT (Kunipia F) with three different
      intercalating agents, namely, piperazine dihydrochloride, 1,3-bis(4
      piperidinylpropane) dihydrochloride and 4,4'-bipiperidine dihydrochloride at 80
      degrees C. Polyamic acid solutions containing various weight percentages of
      organomodified MMT were prepared by reacting 4,4'-(1,1'-biphenyl-4,4'
      diyldioxy)dianiline with bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxylic
      dianhydride in N-methyl-2-pyrrolidinone containing dispersed particles of
      organomodified MMT at 20 degrees C. Nanocomposite films were prepared from these
      solutions by solution casting and heated subsequently at a programmed heating
      rate. These films were transparent and brown in color. The extent of layer
      separation in nanocomposite films depends upon the chemical structure of the
      organoclay. These films were characterized by inherent viscosity, FT-IR, DSC,
      TMA, WAXD, TEM, UV, and TGA. The tensile behavior and surface energy studies were
      also investigated. The nanocomposite films had superior tensile properties,
      thermal behavior, and solvent resistance. Among the three organoclays, piperazine
      dihydrochloride was the best modifier.

PMID- 16108443
TI  - Water-photolysis properties of micron-length highly-ordered titania nanotube
      arrays.
AB  - We report the water photoelectrolysis and photoelectrochemical properties of the
      titania nanotube arrays as a function of nanotube crystallinity, length (up to
      6.4 microm), and pore size. Most noteworthy of our results, under 320-400 nm
      illumination (98 mW/cm2) the titania nanotube-array photoanodes (area 1 cm2),
      pore size 110 nm, wall thickness 20 nm, and 6 microm length, generate hydrogen by
      water photoelectrolysis at a rate of 7.6 mL/hr, with a photoconversion efficiency
      of 12.25%. The energy-time normalized hydrogen evolution rate is 80 mL/hrW, the
      largest reported hydrogen photoelectrolysis generation rate for any material
      system by a factor of four. The highly-ordered nanotubular architecture appears
      to allow for superior charge separation and charge transport, with a calculated
      quantum efficiency of over 80% for incident photons with energies larger than the
      titania bandgap.

PMID- 16108444
TI  - Frequency dependence of the dielectrophoretic separation of single-walled carbon
      nanotubes.
AB  - Dielectrophoresis on single-walled carbon nanotubes in surfactant suspensions has
      been demonstrated to separate metallic from semiconducting tubes by their
      different electric field-induced polarisabilities. Here we report that the
      interaction between SWNTs and the surfactant induces a nanotube surface
      conductance which gives rise to a unique electric field frequency dependence of
      the dielectrophoretic force acting on semiconducting SWNTs. We observe a
      surfactant concentration dependent crossover frequency enabling separation of
      metallic from semiconducting SWNTs at high frequency and deposition of metallic
      and semiconducting SWNTs at low frequency. Proof for the effectiveness of
      separation is given by a comparative Raman spectroscopy study on
      dielectrophoretically deposited tubes excited with two different wavelengths.

PMID- 16108445
TI  - HAADF imaging: an effective technique for the study of nonhomogeneous
      nanostructures.
AB  - Atomic number contrast (Z-contrast) imaging using high-angle annular dark field
      (HAADF) detector, along with high resolution electron microscopy (HREM), is used
      to study the nanostructured metal, semiconductor, mixed oxide, and soft matter
      composites of inhomogeneous nature. A comparison between the HREM and HAADF
      images for the analysis of crystal structure, defects, and compositional
      inhomogenity in those nanostructures has been made. While the HREM technique is
      efficient in determining bulk crystallinity and defect structures, the HAADF
      imaging technique is superior in determining the surface inhomogenity, defect
      structures in the interior of the nanostructures, even at atomic resolution. The
      efficiency of the HAADF imaging technique in determining the surface inhomogenity
      and defect structures is demonstrated for the Au-Pt bimetallic clusters, CdSe
      nanofibers and nanowires, Nb16W18O94 mixed oxide, and polystyrene-mormorillonite
      clay nanocomposites.

PMID- 16108446
TI  - Flow-induced planar assembly of parallel carbon nanotubes and crossed nanotube
      junctions.
AB  - We report the in-situ assembly of carbon nanotubes by chemical vapor deposition
      of hydrocarbon precursor (a solution of ferrocene dissolved in isopropyl
      alcohol). We utilized the vapor stream inside the reaction chamber to comb carbon
      nanotubes along the same direction and obtained two-dimensional (planar) assembly
      of nanotubes with tunable distributions. When the carbon source was flowing at a
      relatively higher rate of approximately 0.2 ml/min, most of nanotubes were driven
      along the vapor flow direction during their growth process and formed a thin
      freestanding mat featured with a parallel arrangement, whereas a lower flowing
      rate (approximately 0.05 ml/min) only resulted in random spider-web structures
      consisting of crossed nanotube junctions with a variety of configurations (e.g.,
      "+", "Y", "T" shapes and twists). The measured direction-dependent electrical
      resistance of these two assemblies was in agreement with respective structures,
      which was anisotropic for parallel nanotubes and nearly isotropic for random
      networks. Such large-area planar carbon nanotube arrays with controlled
      orientation and various junction configurations will facilitate the design and
      fabrication of electronic and mechanical devices.

PMID- 16108447
TI  - Design and performance of EUV resist containing photoacid generator for sub-100
      nm lithography.
AB  - To fulfill the SIA roadmap requirements for EUV resists, the development of
      entirely new polymer platforms is necessary. In order to address issues like Line
      Edge Roughness (LER) and photospeed, we have developed a novel chemically
      amplified photoresist containing a photoacid generator (PAG) in the main chain of
      the polymer. The incorporation of a cationic PAG unit, phenyl methacrylate
      dimethylsulfonium nonaflate (PAG), in the resist backbone showed increased
      sensitivity, when compared with analogous blend PAG resist samples. In addition,
      the overall lithographic performance improved by using the counter anion
      (nonaflate) in the PAG units. The newly synthesized polymer bound PAG resist,
      poly (4-hydroxystyrene-co-2-ethyl-2-adamantyl methacrylate-co-PAG) showed sub-50
      nm features using EUV Lithography.

PMID- 16108448
TI  - CP or not CP?

PMID- 16108449
TI  - Definition and classification of cerebral palsy.

PMID- 16108450
TI  - Education and employment prospects in cerebral palsy.
AB  - Parents and paediatric neurologists need information on the long-term social
      prognosis of children with cerebral palsy (CP). No large population-based study
      has been performed on this topic. On 31 December 1999, to find predictors in
      childhood of subsequent education and employment, 819 participants with CP born
      between 1965 and 1978 (471 males; mean age 28y 10 mo, SD 4y, range 21 to 35y) in
      the Danish Cerebral Palsy Registry were compared with 4406 controls without CP
      born between 1965 and 1978 (2546 males; mean age 28y 10 mo, SD 4y, range 21 to
      35y). Diagnostic subtypes of the 819 participants with CP were: 31% hemiplegia,
      43% diplegia, 18% tetraplegia, and 8% other types. Level of motor impairment with
      respect to walking ability was: 62% able to walk without assistance, 21% with
      assistance, and 16% not able to walk (for 1% of study children walking ability
      was not known). Relevant information was obtained from Denmark's unique
      registries. Of the participants with CP, 33% vs 77% of controls, had education
      beyond lower secondary school (i.e. after age 15-16y), 29% were competitively
      employed (vs 82% of controls), 5% were studying, and 5% had specially created
      jobs. Excluding participants with CP with an estimated developmental quotient
      (DQ) of less than 50 or inability to walk at age 5 to 6 years, the odds ratios
      (multivariate analysis) for not being competitively employed were 1.9 for
      diplegia versus hemiplegia, 22.5 for DQ 50 to 85 versus DQ greater than 85, and
      3.7 for those with epilepsy versus those without epilepsy. The severity of motor
      impairment among participants with CP able to walk had just a minor influence.
      Only half the participants with CP who had attended mainstream schooling were
      employed. In conclusion several childhood characteristics seemed to predict long
      term social prognosis.

PMID- 16108451
TI  - Investigation of the timed 'up & go' test in children.
AB  - The timed 'Up & Go' test (TUG) is a test of basic or functional mobility in
      adults which has rarely been used in children. Functional mobility was defined
      for this study as an individual's ability to manoeuvre his or her body capably
      and independently to accomplish everyday tasks. Reliability and validity of TUG
      scores were examined in 176 children without physical disabilities (94 males, 82
      females; mean age 5y 9mo [SD 1y 8mo]; range 3 to 9y) and in 41 young people with
      physical disabilities due to cerebral palsy or spina bifida (20 males, 21
      females; mean age 8y 11mo [SD 4y 3mo], range 3 to 19y). Mean TUG score for
      children without physical disability was 5.9s (SD 1.3). Reliability of the TUG
      test was high, with intraclass correlation coefficients (ICC) of 0.89 within
      session, and 0.83 for test-retest reliability. Mean score of the group aged 3 to
      5 years was significantly higher (6.7s SD 1.2) than that of the older group
      (5.1s, SD 0.8; p=0.001). Scores in the younger group reduced significantly over a
      5-month follow-up period (p=0.001), indicating that the TUG was responsive to
      change. Within-session reliability of the TUG in young people with disabilities
      was very high (ICC=0.99). There were significant differences in TUG scores
      between children classified at levels I, II, and III of the Gross Motor Function
      Classification System (p=0.001). TUG scores showed a moderate negative
      correlation with scores on the Standing and Walking dimensions of the Gross Motor
      Function Measure (n=22, rho=-0.52, p=0.012). There was no significant difference
      in TUG scores between typically developing male and female children. The TUG can
      be used reliably in children as young as 3 years using the protocol described in
      this paper. It is a meaningful, quick, and practical objective measure of
      functional mobility. With further investigation, the TUG is potentially useful as
      a screening test, an outcome measure in intervention studies for young people
      with disabilities, a measure of disability, and as a measure of change in
      functional mobility over time.

PMID- 16108452
TI  - Explicit memory performance in infants of diabetic mothers at 1 year of age.
AB  - The aim of the present research was to investigate the impact of abnormal fetal
      environment on explicit memory performance. Based on animal models, it was
      hypothesized that infants of diabetic mothers (IDMs) experience perturbations in
      memory performance due to exposure to multiple neurologic risk factors including:
      chronic hypoxia, hyperglycemia/reactive hypoglycemia, and iron deficiency. Memory
      performance, as measured by the elicited/deferred imitation paradigm, was
      compared between 13 IDMs (seven females, six males; mean age 365 days, SD 11) and
      16 typically developing children (seven females, nine males; mean age 379 days,
      SD 9). The IDM group was characterized by shorter gestational age (mean 38w, SD
      2), greater standardized birthweight scores (mean 3797g, SD 947), and lower iron
      stores (mean ferritin concentration 87C microg/L, SD 68) in comparison with the
      control group (mean gestational age: 40w, SD 1; mean birthweight: 3639g, SD 348;
      mean newborn ferritin concentration 140 microg/L, SD 46). After statistically
      controlling for both gestational age and global cognitive abilities, IDMs
      demonstrated a deficit in the ability to recall multi-step event sequences after
      a delay was imposed. These findings highlight the importance of the prenatal
      environment on subsequent mnemonic behavior and suggest a connection between
      metabolic abnormalities during the prenatal period, development of memory,
      circuitry, and behavioral mnemonic performance.

PMID- 16108453
TI  - Short-term memory and vocabulary development in children with Down syndrome and
      children with specific language impairment.
AB  - A longitudinal comparison was made between development of verbal and visuo
      spatial short-term memory and vocabulary in children with Down syndrome (DS),
      children with specific language impairment (SLI), and typically developing
      children as a control group. Participants were 12 children with DS (6 males, 6
      females; mean chronological age 9y 9mo [SD 2.8 mo], range 8y 6mo to 11y 4mo);
      nine children with SLI (4 males, 5 females; mean chronological age 3y 9mo [SD
      4.8mo], range 3y 3mo to 4y 5mo); and 12 typically developing children (5 males, 7
      females; mean chronological age 4y 4mo [SD 3.9mo], range 3y 3mo to 4y 3mo).
      Participants were matched on mental age (mean mental age 4y 3mo). All
      participants completed verbal short-term memory, visuo-spatial short-term memory,
      and expressive and receptive vocabulary tasks on three occasions over 1 year.
      Similarities were seen in the clinical groups for verbal short-term memory. There
      was some evidence of difficulty in visuo-spatial short-term memory in the
      children with SLI relative to the other groups, but all three groups showed
      overlap in visuo-spatial short-term memory performance. At the final time-point
      vocabulary performance in the clinical groups was similar; the typically
      developing children showed higher vocabulary abilities than both clinical groups.

PMID- 16108454
TI  - Effect of a social skills training group on everyday activities of children with
      attention-deficit-hyperactivity disorder.
AB  - This preliminary study compared the daily living skills of children with and
      without attention-deficit-hyperactivity disorder (ADHD), and the influence of a
      social skills training group on these skills. Twenty-seven children with ADHD (2
      females, 25 males; age range 5 to 8y, mean 6y 6mo, SD 10mo), and 24 children
      without ADHD (8 females, 16 males; age range 5 to 8y, mean 6y 11mo, SD 10mo)
      performed the Assessment of Motor and Process Skills (AMPS). Fourteen of the
      children with ADHD used medication daily. Nine of the total group with ADHD were
      randomly selected to attend group treatment which focused on social skills
      training, through meaningful occupations (e.g. art, games, cooking). Children
      were evaluated at the beginning of group treatment and after 10 sessions. Ten
      children without ADHD were evaluated at similar intervals. Children with ADHD
      initially achieved significantly lower scores on the AMPS in all process skills
      (p<0.001) and in the coordination motor subtest (p<0.005) than children without
      ADHD. Children with ADHD significantly improved from the first to the second
      evaluation and no longer differed from the children without ADHD after treatment
      (p<0.008). The results emphasize the need for a focus upon occupation in
      assessment and treatment of children with ADHD.

PMID- 16108455
TI  - Effect of epilepsy on psychomotor function in children with uncomplicated
      epilepsy.
AB  - This study assessed the impact of epilepsy on motor function in children. We
      aimed to analyze the effect in uncomplicated epilepsies (cryptogenic partial and
      idiopathic generalized epilepsy). A group of 87 children with epilepsy (47 males,
      40 females; mean age 8y, standard deviation [SD] ly 9mo, range 4y 11mo to 12y
      11mo), but without learning disability* or other neurological comorbid disorders,
      was compared with a control group of 107 children (76 males, 31 females; mean age
      8y 4mo, SD 2y 2mo, range 4y 7mo to 12y 2mo). The differences in main motor skills
      and psychomotor speed were analyzed using the Movement ABC and computerized
      measures for simple reaction times and finger tapping. No significant difference
      in motor function was found. The overall psychomotor development of children with
      epilepsy is comparable to controls. However, a significant slowing of psychomotor
      speed in the group with epilepsy was reported. No relation with antiepileptic
      drug treatment was demonstrated and no difference in psychomotor speed between
      different types of epilepsy was found. The existence of a condition leading to
      excessive neuronal discharge leads to a general cortical inhibition. The slowing
      of psychomotor speed in children with uncomplicated epilepsy may be the
      behavioural presentation of this inhibition.

PMID- 16108456
TI  - Characteristics of fetal anticonvulsant syndrome associated autistic disorder.
AB  - The aim of this study was to evaluate the clinical features and frequency of
      autistic disorder or Asperger syndrome (AS; according to Diagnostic and
      Statistical Manual of Mental Disorders, 4th edition [DSM-IV] criteria) in
      children exposed to anticonvulsant medication in utero. During a 20-year study
      period, 626 children were born in Aberdeen to mothers taking antiepileptic drugs
      (AEDs). The study examined long-term effects of prenatal exposure to AEDs in 260
      children (122 males, 138 females). Of these, 26 (16 males) were reported by
      parents to have social or behavioural difficulties. Eleven children (6 males, 5
      females) fulfilled the DSM-IV criteria for autistic disorder and one (female)
      fulfilled the DSM-IV criteria for AS. These children comprised 4.6% of the
      exposed children studied, and 1.9% of all exposed children born during the study
      period. Mean age of these children at diagnosis was 5 years 4 months (SD 2y 11mo)
      and 9 years 10 months (SD 3y 10mo) at the time of this study. Other children from
      the group of 26 had difficulties in areas of speech and language development and
      social communication but did not meet the criteria for an autism spectrum
      disorder (ASD). Sodium valproate was the drug most commonly associated with
      autistic disorder, five of 56 (8.9%) of the study children exposed to sodium
      valproate alone had either autistic disorder or AS. It was concluded that
      prenatal exposure to anticonvulsant medication is a risk factor for the
      development of an ASD. Fetal anticonvulsant syndrome associated autistic disorder
      is characterized by an even sex ratio, absence of regression or skill loss, and
      language delay in the absence of global delay.

PMID- 16108457
TI  - Pilot survey of Hashimoto's encephalopathy in children.
AB  - Hashimoto's encephalopathy (HE) is a steroid responsive, relapsing encephalopathy
      associated with thyroid autoantibodies. Paediatric literature mainly consists of
      case reports of the disease. A questionnaire survey of 68 consultant paediatric
      neurologists was undertaken through the British Paediatric Neurology Association
      in 2002 to gather preliminary data about this condition. The response rate was
      68% and a total of ten patients were identified: nine from the UK and one from
      Ireland. Complete clinical details were available on eight patients (seven
      females and one male). Age at presentation ranged from 10 to 15 years (mean 12y
      7mo, SD 1y 1mo). Presenting features included seizures (n=7/8), encephalopathy
      (n=7/8), cognitive decline (n=4/8), behavioural problems (n=3/8), psychosis
      (n=2/8), myoclonus (n=1/8), and tremors (n=1/8). All had thyroid autoantibodies
      and four were also hypothyroid at diagnosis. One patient became hypothyroid
      during follow-up. Electroencephalograms (EEGs) showed high amplitude slow
      background rhythms in all patients, and one patient also had focal spikes.
      Cognitive deficits were identified in four patients and persisted in one over 2
      years of follow-up. Six patients improved with steroids and two improved
      spontaneously. Two had relapsing courses during follow-up afer diagnosis (range
      12-48 months). HE may be currently under-recognized in children and increased
      awareness can result in prompt diagnosis and treatment. Steroid therapy appears
      to be beneficial. Neuropsychological assessment is required in all cases and may
      guide steroid therapy. Long-term prognosis for cognition remains guarded at this
      time.

PMID- 16108458
TI  - Stimulant medication in 47,XYY syndrome: a report of two cases.
AB  - In two males, 11 and 12 years of age, referred for attention-deficit
      hyperactivity disorder (ADHD), 47,XYY syndrome was diagnosed. A team that
      included a neuropsychologist, a physiotherapist, and a physician examined them.
      Stature (patients were above 97.5% height for age), muscle consistency, and
      tremor indicated chromosome analysis. Psychological tests results did not fully
      fit the ADHD diagnosis. On the basis of our clinical observation we felt that
      stimulant medication was indicated. Administration of methylphenidate led to
      improved motor and cognitive functions as well as social adaptation in both
      patients. We suggest that this treatment might well be considered in clinically
      similar patients with XYY sex chromosomes; we further suggest that learning
      problems in such individuals may be related to ADHD.

PMID- 16108459
TI  - Cognitive function in tetraplegic cerebral palsy with severe motor dysfunction.

PMID- 16108460
TI  - Conservative interventions for positional plagiocephaly: a systematic review.
AB  - This review aimed to synthesize current research evidence to determine the
      effectiveness of conservative interventions for infants with positional
      plagiocephaly. A systematic review was conducted, where papers were sourced from
      13 library and internet databases. Research was included if published in English
      between 1983 and 2003. Level of evidence and quality of each paper was assessed
      to determine studies' magnitude of inherent bias. Results were synthesized in a
      narrative format and were considered with respect to homogeneity of participants,
      response rate, and outcome measures. Sixteen papers met inclusion criteria: 12
      were case series and four were comparative studies. The methodological quality of
      the studies was moderate to poor, thus their results should be interpreted with
      caution. A consistent finding was that counterpositioning +/- physiotherapy or
      helmet therapy may reduce skull deformity; however, it was not possible to draw
      conclusions regarding the relative effectiveness of these interventions. Further
      investigation is required to compare the effect of helmet therapy with
      counterpositioning alone or when combined with physiotherapy. First, there is a
      need to develop an outcome measurement battery which incorporates
      psychometrically-sound measures from the perspectives of clinicians and patients.

PMID- 16108462
TI  - Disaster may be closer than you think. Are you ready?

PMID- 16108463
TI  - Good leadership requires good conflict management.

PMID- 16108461
TI  - Proposed definition and classification of cerebral palsy, April 2005.
AB  - Because of the availability of new knowledge about the neurobiology of
      developmental brain injury, information that epidemiology and modern brain
      imaging is providing, the availability of more precise measuring instruments of
      patient performance, and the increase in studies evaluating the efficacy of
      therapy for the consequences of injury, the need for reconsideration of the
      definition and classification of cerebral palsy (CP) has become evident.
      Pertinent material was reviewed at an international symposium participated in by
      selected leaders in the preclinical and clinical sciences. Suggestions were made
      about the content of a revised definition and classification of CP that would
      meet the needs of clinicians, investigators, and health officials, and provide a
      common language for improved communication. With leadership and direction from an
      Executive Committee, panels utilized this information and have generated a
      revised Definition and Classification of Cerebral Palsy. The Executive Committee
      presents this revision and welcomes substantive comments about it.

PMID- 16108464
TI  - Does technology pay? (Yes).

PMID- 16108465
TI  - E-mail ease. Case study: online portal for health care.

PMID- 16108466
TI  - All certification, all the time. ABMS moves from physician-certification renewal
      to maintenance of certification.

PMID- 16108467
TI  - Your people make the difference. Administrative, clinical staff key to success in
      rural practices.

PMID- 16108468
TI  - Goal-oriented. A strategic planning case study.

PMID- 16108469
TI  - The hereafter. Why IT security matters to your practice even after the HIPAA
      Security Rule deadline.
AB  - The days when taking care of security meant locking filing cabinets and
      installing a reliable burglar alarm are long gone. But just what is the role of a
      practice's administrator to ensure that its information technology is secure?
      This article helps administrators answer that question.

PMID- 16108470
TI  - It takes more than a smile to smooth rough edges. Manage risk by focusing on
      customer service.
AB  - Good customer service is much more than smiling and being friendly with your
      patients. Clinical operating risk can fluctuate with the demand for care and
      variations in staffing, resources and technology. By making patient safety part
      of your customer service training and business practices, you can mitigate risk
      and create happier patients.

PMID- 16108471
TI  - Reading the tea leaves. Making sense of new legal guidance on ancillary services.
AB  - Medical groups continue to explore ancillary service development to address
      patient care and generate revenue. However, the regulatory environment
      surrounding ancillary service arrangements changed as the Department of Health
      and Human Services Office of Inspector General rejected a "turn-key" pathology
      laboratory service arrangement in Advisory Opinion 04-17 (AO-04-17). This article
      considers how this and other recent guidance affects what medical groups can and
      cannot do regarding ancillary services.

PMID- 16108472
TI  - Key developments in endocrinology.

PMID- 16108473
TI  - The patient with polycystic ovary syndrome.

PMID- 16108474
TI  - Managing hypoglycaemia.

PMID- 16108475
TI  - Goitres and thyroid carcinoma.

PMID- 16108476
TI  - Urticaria.

PMID- 16108477
TI  - Casebook: psoriasis.

PMID- 16108479
TI  - [Progression and direction of humanized antibody research].
AB  - After its advent, monoclonal antibody has gone an uneven way to its present wide
      applications in clinical practices, during which the humanized antibody set an
      important milestone accompanying a series of technique renovations, such as PCR
      technique, phage display and transgenic animals. Humanized antibody has developed
      from chimeric antibody and reshaped antibody to the present fully human antibody.
      Humanization of murine antibodies has been the future direction of therapeutic
      antibodies and this can be reflected from the fact that humanized antibodies or
      even human antibodies have made up majority of the therapeutic antibodies both in
      clinical test and in the market. The present techniques have enabled the
      production of fully human antibodies and given chances to the arising of antibody
      derivatives. They not only overcome the deficiency in application of murine
      antibody with different strategies, but also provide more weapons for human
      therapeutics. However, modifications of monoclonal antibody aiming at clinical
      applications need more research work in the mechanisms of antibody effector
      system, as well as comprehensive understanding in regulation of human immune
      system.

PMID- 16108481
TI  - [Using green fluorescent protein as a reporter to monitor elimination of
      selectable marker genes from transgenic plants].
AB  - In genetic modification of plants, once the transformants are obtained, selection
      markers are no longer required in mature plants. At present, the Cre/lox site
      specific recombination system is most widely used to eliminate the selectable
      marker genes from the transgenic plants. In this study, attempt was made to
      favour the selection of marker-free plants in the re-transformation method. Green
      fluorescent protein (GFP) can be directly visualized in living cells, tissues or
      organisms under UV illumination. This advantage of GFP is exploited in the
      development of a practical approach in which GFP is used as a visual marker to
      monitor the removal of the selectable marker gene from transgenic plants. For
      that purpose, the pGNG binary vector was constructed, in which the GFP gene (gfp)
      was linked to the expression cassette Nos P-nptII-NosT and the two units were
      cloned between two directly-orientated lox sites. The CaMV 35S promoter was
      placed before the first lox site and used to drive GFP expression. The beta
      glucuronidase gene (gus) of Escherichia coli was cloned behind the second lox
      site without a promoter, thus would not be expressed in this position. Tobacco
      plants were first transformed with pGNG and selected on kanamycin (Kan)
      containing media. Regenerated transgenic shoots were readily singled out by GFP
      fluorescence. The GFP-expressing plants were then re-transformed with pCambia1300
      Cre containing hygromycin phosphotransferase gene (hpt) as a selectable marker
      gene. The Cre-mediated recombination resulted in the elimination of lox-flanked
      genes, herein gfp and nptII, from the plant genome and brought the GUS gene next
      to the 35S promoter. Our data demonstrated that transgenic plants free of nptII
      were easily selected by monitoring the loss of green fluorescence, and at the
      same time, GUS (here as a target protein) was expressed in the nptII-free plants.
      Finally, hpt and cre were removed from the progenies of the nptII-free plants by
      gene segregation.

PMID- 16108480
TI  - [The potential role of nuclear matrix attachment regions (MARs) in regulation of
      gene expression].
AB  - Gene transfer technology is being used to enhance agronomic performance or
      improve quality traits in a wide variety of crop species. However, it is
      sometimes severely handicapped by difficulty in obtaining material in which
      transgene expression is predictable and stable over many generations. Because
      integration seemed to occur randomly in the plant genome, it was thought that
      some transgenes would be integrated in a relatively uncondensed,
      transcriptionally active chromatin environment, while others in a condensed,
      transcriptionally inert chromatin structure. Nuclear matrix attachment regions
      (MARs) are defined as DNA sequences that bind preferentially to the proteins of
      the nuclear matrix. They typically are localized at the borders of gene domains,
      implicating them in the formation of individual loops of higher order chromatin
      structure and transcription regulation. When MARs are positioned on either side
      of a transgene their presence usually results in higher and more stable
      espression in transgenic plants, most likely by minimizing gene silencing. In
      this review, we focus mainly on novel findings and our observations concerning
      the function of MARs in transcription regulation. Our objective is not only to
      summarize the current data and present several possible models to explain MAR
      effects on the transcription regulation, but also to point out some open
      questions involving the utilization of MARs in constructing high efficient
      expression vectors.

PMID- 16108482
TI  - [Knockout of the ptsG gene in Escherichia coli and cultural characterization of
      the mutants].
AB  - Metabolic engineering provide powerful tools for the systematic manipulation of
      cellular metabolic activities. The ptsG gene for glucose-specific transporter
      Enzyme II CBGlc of the phosphotransferase system was knock-out so as to reduce
      the accumulation of acetic acid in the high cell-density culture of Escherichia
      coli on excess glucose. The chloramphenicol-resistant cassette with short shared
      sequences on both ends generated by PCR was electroporated into Escherichia coli
      DH5alpha and JM109. Recombination between linear DNA cassettes and Escherichia
      coli chromosomes took place by Red recombinase functions. Therefore, the ptsG
      gene was disrupted to construct the mutants called DH5alphaP and JM109P. There
      was no difference between the mutants and parent strains in LB media.However, in
      LB media supplemented with glucose, the mutants of Escherichia coli deficient in
      ptsG showed greater biomass, together with exploiting more glucose. The maximal
      cell density obtained with DH5alphaP was approximately 3 times more than that of
      DH5alpha, then the result of JM109P increased fourfold. The products of
      recombinant protein TNF respectively accounted for 24.3% of total cellular
      protein in DH5alphaP with A600 8.28 and 20.8% of total cellular protein in JM109P
      with A600 7.62. The specific volume expression amount of TNF was greater in the
      ptsG mutant than in its parent strain. These results demonstrate that the ptsG
      mutant strains will be available for high cell-density culture.

PMID- 16108483
TI  - [Expression of goat beta-casein gene targeting vector in mammary gland cell].
AB  - The study of mammary gland bioreactor is in the ascendant. In order to generate
      transgenic goats of well-controlled expression of exogenic genes, we constructed
      a human lactoferrin (hLF) gene targeting vector containing promoter, exon 1,
      intron1 and some of exon 2 (about 6.1 kb fragment) and exon 6 approximately 9
      (about 3.3 kb fragment) of the goat beta-casein gene as well as hLF minigene, neo
      gene inserted into them and tk gene ligated to the 3' end of the construct. The
      9.4 kb goat genomic sequences as homologous arms were initially amplified by PCR
      with local goat tissue DNA. The expression vector was named pBC-tk-neo-hlf. Then
      the recombinant plasmid pBC-tk-neo-hlf containing hLF minigene was transfected
      into mice mammary tumor cell line C127 by liposome, cell clones were selected
      with G418. After proliferating, the transfected cells were induced with insulin,
      luteotropic hormone and hydrocortisone. The result of Western-blotting analysis
      showed that the transfected cells can secrete hLF protein, and the recombinant
      protein expressed in cultured cell supernatant has the similar molecular weight
      as the native protein. The expression level detected by ELISA was 0.21 microg/mL.
      This result indicated that the targeting vector could efficiently direct the
      expression of hLF in mammary cells,and it confirmed the validity of the
      constructed vector. At the same time, C127 cell line proved to be useful for
      evaluating the regulation of a foreign gene expression in mammary gland specific
      expression vector.

PMID- 16108484
TI  - [Expression of TMP Fc in Pichia pastoris and identification of its biological
      activity].
AB  - The DNA coding for the fusion protein of thromobopoietin mimetic peptide (TMP)
      and human IgG1 Fc fragment was amplified from recombinant plasmid pET28a/TMPFc,
      inserted into pPICZalphaA and transformed into Pichia pastoris using
      electroporation. The recombinants of correct phenotype were identified after
      screening on MDH and MMH culture medium. The fusion gene was verified with PCR
      and western blot. MTT method was used to test the activity of TMPFc in promoting
      the growth of Ba/ F3-mpl cell. The TMPFc with a 64 000 molecular weight was a
      secretary protein in the system and its expression amounted to 65% of the total
      protein in the medium supernatant. The TMPFc showed a promotive effect on the
      growth of Ba/F3-mpl in vitro. A significant portion of the secretary protein
      existed as dimer, which provided material for studying the dimer in future.

PMID- 16108485
TI  - [Cloning and expression of hTRF1 in Escherichia coli and preparation of
      polyclonal antibody].
AB  - Human telomeric repeat binding factor 1(TRF1) contains one Myb-type DNA-binding
      repeat and an amino-terminal acidic domain. It can bind to the duplex array of
      TTAGGG repeats at chromosome ends and is shown to be important in preserving
      genomic stability, maintaining cell proliferative capacity, and blocking the
      activation of DNA-damage cell cycle checkpoints. Interestingly, the double strand
      DNA breaks sensor ATM interacts with and phosphorylates Pin2/TRF1 and inhibits
      its function after DNA damage. Are there some proteins else that can interact
      with TRF1 and influence its function? In order to analysis the interaction
      between TRF1 and other proteins, we must prepare the antiserum that can recognize
      the endogenous TRF1 of cell lysates. TRF1 cDNA was amplified using cDNA Library
      of HeLa cell by PCR and cloned into pUCm-T vector. Sequence analysis reveals
      identity to the GenBank report. The TRF1 cDNA was subcloned into expression
      vector pET-28c(+) and expressed in E. coli as a fusion protein of 65 kD. The
      recombinant TRF1 can express in the supernatant (about 12.3% in total protein) on
      the induction of 0.5 mmol/L IPTG at 37 degrees C for 3 hours. Western-blot
      analysis showed the recombinant protein can react with TRF1 polyclonal antibody
      sc-6165 (from Santa Cruz Company). His6-TRF1 was purified by Ni(2+) -NTA resin
      affinity chromatography made by ourselves and showed to be homogeneity in SDS
      PAGE. Rabbits were immunized for four times to prepare polyclonal antibody. The
      unpurified antiserum can recognize the overexpressed TRF1 with myc-tag and the
      endogenous Pin2/TRF1 of cell lysate by Western-blot at 1:1000 dilution. At 1:400
      dilution, the antiserum can interact with endogenous TRF1 by Immunofluorescence
      cell staining analysis. The endogenous TRF1 in different cell lines, such as
      HepG2, 803, MCF7 and HeLa, locates in the nucleus. The soluble expression TRF1
      and preparation of its antibody lay the foundation to study it further.

PMID- 16108486
TI  - [Expression of delta6-fatty acid desaturase gene from Mortierella alpina in
      Pichia pastoris].
AB  - Gamma-linolenic acid (GLA, C18:3delta6 ,9,12), an essential polyunsaturated fatty
      acid, plays an important role in hormone regulation and fatty acid
      metabolization. Delta6-fatty acid desaturase (D6D) is the rate-limiting enzyme of
      the desaturation of linoleic acid (C18:2delta9,12) in the production of gamma
      linolenic acid. A deficiency of GLA may have occurred when delta6-fatty acid
      desaturase activity decreases in aging, stress, diabetes, eczema, and some
      infections. To establish a new expression system for delta6-fatty acid desaturase
      gene in Pichia pastoris, which is an increasingly popular heterologous gene
      expression system, a gene encoding delta6-fatty acid desaturase from Mortieralla
      alpina was isolated by PCR amplification. The PCR product was then digested by
      EcoR I and Not I and subcloned into the intracellular expression vector pPIC3.5K
      to generate the recombinant vector pPIC3.5K-MA6. The resulting vector was
      linearized by Sac I and electroporated into P. pastoris SMD1168 (his- pep-) host
      cells. After electroporation, aliquots were spreaded on the MDS plates and
      incubated at 30 degrees C for three days until colonies appeared. Those
      transformants were subsequently screened for clones with high copy number by
      using the YPD plates containing G418. To identify the D6D constructs that were
      produced, chromosomal DNA of the transformants were prepared and used as template
      for PCR with the primer 5' AOX and 3' AOX. The PCR product of Mut+ recombinants
      was shown as a band of 1.38 kb of D6D gene and the product of 2.2 kb of AOX1
      gene, while the product of Mut(s) transformants only was shown as a band of 1.38
      kb of the D6D gene.To further confirm the transformants containing a functional
      D6D gene, the positive clones were selected and induced by methanol for
      expression. Those induced cultures were taken for analyses of the intracellular
      fatty acid composition by GC. The resultant chromatograms of fatty acid methyl
      esters showed that a novel peak was detected, which was not apparent in the case
      of control. Comparisons of the retention times of the newly yielded peaks with
      those of authentic standards have anticipated that the fatty acid is GLA. And
      this prospects was positively supported by definitive assignments of the
      compounds by GCMS analyses. Thus, the active delta6-fatty acid desaturase was
      expressed intracellularly in P. pastoris and gamma-linolenic acid reached 16.26%
      of the total fatty acid in recombinant P. pastoris strains. It was the first
      report about the expression of Mortieralla alpina D6D gene in P. pastoris.

PMID- 16108487
TI  - [Identification of genes that are specifically/preferentially expressed in
      developing cotton fibers by mRNA fluorescence differential display (FDD)].
AB  - Fluorescence differential display (FDD) technique was used to identify genes that
      are specifically or preferentially expressed in different developmental stages of
      cotton fiber cells. One hundred and nine differentially displayed cDNA fragments
      were isolated using 9, 21 and 27 DPA (days postanthesis) fibers as experimental
      materials. By a combination of two rounds of reverse Northern hybridization and
      Northern blot analyses, a number of such cDNA fragments were proved to represent
      fiber-specific/preferential genes. Sequencing determination and database
      searching indicated that most of these genes are novel. This work is an important
      step towards cloning the full-length cDNAs and characterizing the cellular
      functions of aforementioned genes in fiber development.

PMID- 16108488
TI  - [Construction of combined site-directed random mutation libraries of recombinant
      human lymphotoxin].
AB  - To construct the combined site-directed random mutation library of recombinant
      human Lymphotoxin (rhLT) for in vitro molecular evolution study, and to study the
      structure and function relationship. The random point mutations at the sites of
      46,106 and 130 were individually generated by overlap PCR amplification with the
      random nucleotide primers. The three point mutations were combined and cloned
      into pMD-18T vector to construct the combined mutation library. DNA sequencing
      was used to evaluate the diversity and randomness of the mutation sites. The
      combined mutation library was re-engineered, inserted in prokaryotic expression
      vector pBV220, transformed and expressed in Escherichia coli strain DH5alpha. The
      biological activity of some of the mutants was tested in 1929 mouse fibroblast
      cells. As much as 1.5 x 10(5) clones were obtained, which represents 4.5 times of
      the complete mutation libraries at 99% confidence. Sequencing 50 clones revealed
      no obvious bias in the nucleotide and amino acid mutations at the sites. Among
      the 30 expressed samples underwent for the bioassay, 70% (21 samples) were
      inactive, 23.3% (7 samples) had lower activity than rhLT, the remaining 6.7% (2
      samples) had higher activity than rhLT. The combined site-directed random
      mutation library of rhLT has been constructed successfully. In combination with
      phase display, the library is ready for in vitro molecular evolution study.

PMID- 16108489
TI  - [Expression and purification of three fusion proteins containing a single B-cell
      epitope (beta5, beta9 or beta8) of human chorionic gonadotropin beta subunit].
AB  - The possibility of using a subunit or fragment of human chorionic gonadotropin
      (hCG) as an immunogen for birth control has been actively explored for many
      years. This protein homone is produced by the fertilized egg and is required for
      implantation of the blastocyst into the maternal uterus and the maitenance of
      pregnancy. In previous studies, several bio-synthesized hCG chimeric peptides
      (CP) that contain three linear B-cell epitopes (beta5, beta9 and beta8) of beta
      hCG subunit together with various foreign 'promiscuous' T-cell epitopes were
      constructed and expressed as potential new hCG vaccine immunogens. In order to
      detect antibodies to each of the individual B-cell epitopes present in the animal
      antiserum raised against the hCG CPs, we decided to construct three recombinant
      proteins, each contains a single target B-cell epitope (betaE) of beta-hCG. Two
      sets of DNA fragments were chemically synthesized encoding the beta5, beta9 and
      beta8 epitopes (betaE) 45 approximately 52, 113 approximately 116 or 133
      approximately 144 of beta-hCG subunit and were inserted into the downstream of
      streptavidin (Stv) gene in pTSA18 separately, with or without an extra TAA codon
      at the 3'-terminals of the genes. SDS-PAGE analysis revealed that only Stv-betaE
      (-beta5, -beta9 or -beta8) fusion genes set with the TAA codon can be expressed
      in E. coli BL21 (DE3) pLysS strain at high level after 1mM IPTG induction for 4
      hours. Additionally, these fusion proteins can all be recognized by specific
      polyclonal antiserum (RS-4157) generated upon immunization with the loop peptide
      38 approximately 57 of beta-hCG, monoclonal antibody (mAb) FB12 to beta9 epitope
      and mAb OT3A that specially recognizes reporter sequence 133 approximately 139 of
      beta8 epitope 137 approximately 144. Each of the proteins can be purified to 95%
      relative homogeneity using an improved method of preparative gel polyacrylamide
      gel electrophoresis. The yields were 5 mg per 1 L culture. The three target Stv
      betaE fusion proteins will be useful in determining the immunogenicity of
      designed hCG CPs and hCG vaccines, including hCG DNA vaccines.

PMID- 16108490
TI  - [Construction of cDNA library from NPC tissue and screening of antigenic genes].
AB  - To obtain the NPC-associated antigens, a powerful new method, SEREX (serological
      identification of antigen by recombinant cDNA expression library), was used for
      identifying the antigens eliciting humoral immune response. Before performing
      serological analysis, a high quality cDNA library derived from human
      nasopharyngeal carcinoma (NPC) tissue was constructed. The primary library
      consisted of 3.64 x 10(6) recombinants and the recombinant rate was 94%. For
      better preserving the cDNA library, it was amplified. As a result, the titer of
      the amplified cDNA library was 3.8 x 10(9) pfu/mL. With SEREX method,
      immunoscreening for the detection of reactive clones in the human NPC tissue cDNA
      library was performed with autologous serum. As a result, 23 positive clones
      encoding antigenic genes were obtained after immunoscreening, and the nucleotide
      sequences of cDNA inserts were determined and analyzed with BLAST software in
      GenBank. Results showed that the 23 reactive clones were derived from 16
      different genes. 10 of 16 genes had high homologous to the genes known in
      GenBank, such as RPL31, S100 A2, MT2A, etc. However, there were also 6 genes with
      low homology to the genes known in GenBank. Furthermore, 3 of 6 genes may be
      novel genes. The associations of these genes to NPC and the roles that they
      played in the occurrence and development of NPC should be revealed by further
      research.

PMID- 16108491
TI  - [Identification of an auxin response factor-like protein cDNA from mango
      cotyledon section].
AB  - Auxin-responsive elements (AuxRE) interact with a new class of plant-specific
      transcription factors, auxin response factors (ARFs). Some of ARFs have been
      shown to repress or activate expression of genes with an AuxRE promotor element.
      In Arabidopsis, ARFs play important roles in early embryo development and
      vascular strand formation (ARF5), floral patterning (ARF3) and photo- and
      gravitropic responses (ARF7). Two cut surfaces (distal and proximal) of mango
      (Mangifera indica L. var. Zi-Hua) cotyledon showed different patterns of
      adventitious root formation, with only the proximal cut surface, but not the
      distal one, could be induced to form the roots. Thus, the mango cotyledon is a
      good system for studying adventitious root formation. A cDNA fragment homologous
      to the Arabidopsis auxin response factor-like protein and relates to adventitious
      root formation from the cut sections were isolated using suppressive subtractive
      hybridization (SSH). Two cDNA clones, designated as MiARF1 (mango auxin response
      factor 1 gene, GenBank accession number AY255705) and MiARF2 (mango auxin
      response factor 2 gene, GenBank accession number is AY300808), were identified by
      3'RACE. MiARF1, 3 272bp long, contains an open reading frame (ORF) of 2 523bp,
      5'UTR of 285bp and 3'UTR of 464bp, MiARF2, 1 474bp long, contains an ORF of
      981bp, 5' UTR of 285bp and 3'UTR of 208bp. The deduced MiARF1 and MiARF2 are
      homologues of auxin response factor (ARF) family of transcriptional regulators,
      and show high similarity to ARF of Arabidopsis in conserved domains. The motifs
      of MiARF1 EL-WHACAGPL in DBD (DNA binding domain) and GDDPW in IV domain are
      identical to that of ARF-like protein of Arabidopsis. MiARF2 is identical to
      MiARF1 in a large part of DBD, but lacks a carboxyl-terminal domain containing
      conserved motifs III and IV. Virtual Northern blot showed that the expression of
      MiARF2 was high in rooting tissue of cultured cotyledon sections but low in non
      rooting tissue, and the MiARF1 was expressed both in the rooting and non-rooting
      tissues. We suggest that the MiARF2 is related to adventitious root formation of
      mango cotyledon section.

PMID- 16108492
TI  - [Preparation of alpha-toxin's protective antigen of clostridium perfringens type
      A and research for its primary immunological protective function].
AB  - Induced by 42 degrees C, the recombinant engineering bacterial pBV/cpa408 was
      highly expressed. After having been pelleted by 80% (NH4)2 SO4 and dialysised,
      the expressed protein was isolated and purified by the gel filtration
      choromatography. Then according to an amount of 1.0 mg/kg, the Kunming Mice (body
      weighted 18g) were immuned with the purified protein by intraperitoneal
      inoculation. One week after the first enhanced immunization, the Kunming Mice
      were attacked with an amount of 1.0MLD alpha-toxin, in which the eight mice
      immuned all survive and the control group all died. During the period of
      immunization, the titre of the mouse's serum antibody was measured by ELISA. One
      week after the first immunization, the titre of the mice's serum antibody was
      1:800, but that of one week after the first enhanced immunization reached to
      1:6400.

PMID- 16108493
TI  - [Construction of two robust CHO cell lines resistant to apoptosis and adapted to
      protein-free medium by over-expression of Igf-1/bcl-2 or bcl-2/cyclin E genes].
AB  - Serum used widely in mammalian cell culture is also a potential source of
      bacterial, mycoplasmal and viral contaminations. In addition, the complex
      biological components in serum make harder the subsequent product recovery
      process. High cost, high batch variation and potential source limitation are
      among the other shortcomings. So serum-free or even protein-free medium are
      preferable for recombinant protein production. However, without serum to provide
      essential components such as hormones, growth factors and binding proteins, cells
      are easy to die. In this study, CHO-dhfr- cells were genetically engineered to
      make them adapted to IMEM, a protein-free medium, and resistant to apoptosis. The
      genes in choice are insulin-like factor (Igf-1), Bcl-2 and cyclin E. Bcl-2 is a
      mitochondrial membrane-integrated protein. It can block the release of cytochrome
      c by maintaining the integrity of mitochondrial membrane, and thus inhibit
      apoptosis. Igf-1 is similar both in structure and function to insulin, a growth
      factor added to serum-free medium to promote cell growth and is the only protein
      component in many currently used serum-free media. cyclin E is a cell cycle
      protein expressed continuously in G1 phase. When cyclin E accumulates to certain
      amount, cell cycle was driven to S phase. So cyclin E is a proliferation
      promoting protein. By co-express Igf-1/Bcl-2 or Bcl-2/ cyclin E in CHO-dhfr-
      cells with a dicistronic expression vector, we constructed two cell lines: CHO-IB
      and CHO-BC. The high expression of each protein was confirmed by Western blot and
      flow cytometry. Apoptosis was analyzed by flow cytometry and DNA ladder
      detection, and the two cell lines were both found much more resistant to
      apoptosis induced by withdrawal of serum or addition of actinomycin D than the
      CHO-dhfr- parent cell. Cell proliferation assay by MTT method showed that the two
      cell lines proliferated much faster than CHO-dhfr- in IMDM medium without serum.
      Continuously culture assay proved that the two cell lines grow very well in IMEM
      protein-free medium supplemented with fibronectin and vitronectin to ease
      adherence. When compared to CHO-dhfr-, the two cell lines exhibited much more
      viable cell numbers and faster growth rate.

PMID- 16108494
TI  - [Mammalian gene-transfer and expression efficiencies of baculovirus bacV-CMV
      EGFPA].
AB  - It has been reported that baculoviruses could serve as a new gene-transfer
      vehicle for mammalian cells. We have previously constructed recombinant
      baculovirus BacV-CMV-EGFPA and have proven that mammalian cells could be
      effectively infected by the recombinant baculovirus. In this report, we studied
      the efficiency of baculovirus to deliver exogenous gene into twenty mammalian
      cells, including twelve human cell lines (WI-38, Hela, HepG2, 293, PLC/PRF/5,
      143B, MCF-7, BGC-223, DMS 114, CNE, Raji, LCL-cm), seven murine cell lines (BNL
      1ME A.7R.1, CHO-K1, L-929, JC, PT67, NIH3T3, P815) and one monkey cell line
      (CV1). Results showed that most mammalian cell lines could be transduced by the
      recombinant baculovirus, the transduction efficiencies of the human and monkey
      cell lines were markedly higher than that of murine cell lines, and the
      transduction efficiencies in adherent culture cell lines higher than that of
      suspend culture cell lines, implying that the infection efficiency of the
      baculovirus may be correlative with the organism used and the growth properties
      of the cell lines. The plasmid pcDNA3. 1-EGFP, which contains the CMV promoter
      and EGFP reporter gene, was next transfected by LipofectAMINE into a number of
      mammalian cells, especially those cells that were low in the baculovirus
      transfection. Results showed that the CMV promoter could effectively direct the
      expression of the reporter gene in these mammalian cells. Therefore the gene
      expression efficiencies in different mammalian cell lines by the recombinant
      baculovirus which contains the same CMV promoter were dictated by the ability of
      the baculovirus to enter the cell lines. This study suggested that the
      recombinant baculovirus vector is more suitable for gene expression in primate
      adherent culture cells than in murine cells and suspend culture cells.

PMID- 16108495
TI  - [Overexpression of Escherchia coli phytase with high specific activity].
AB  - High-level expression of phytase with high specific activity is an effective way
      to improve phytase fermentation potency and reduce its production cost. The gene
      appA encoding Escherchia coli phytase AppA with high specific activity was
      modified and artificially synthesized according to the bias in codon choice of
      the high expression gene in Pichia pastoris without changing the amino acid
      sequence of the AppA. The modified gene, appA-m, was inserted in the Pichia
      pastoris expression vector pPIC9, then introduced into the host Pichia pastoris
      by electroporation. The Pichia pastoris recombinants for phytase overexpression
      were screened by enzyme activity analysis and SDS-PAGE. The result of Southern
      blotting analysis of the recombinant yeast indicated that only one copy of the
      appA-m gene was integrated into the genome of Pichia pastoris. The result of
      Northern analysis of the recombinant yeast showed that the modified gene was
      effectively transcribed. SDS-PAGE analysis of the phytase expressed in Pichia
      pastoris revealed that the phytase was overexpressed and secreted into the medium
      supernatant. There are three phytase proteins with apparent molecular weight in
      approximately 50kD, 52kD and 54kD respectively in the media, which are larger in
      the size than the native phytase from E. coli. The results of N-terminal
      sequecing and deglycosylation of the expressed phytase in Pichia pastoris proved
      that the expressed phytase were glycosylated protein with different glycosylation
      degree. The expressed phytase Pichia pastoris shared similar pH and temperature
      optima to those of the natural phytase from E. coli and had highly resistant to
      pepsin digestion. In 5-L fermentor, after induced by 0.5% methanol for 120 h, the
      expression level of phytase protein was 2.5 mg/mL, and the phytase activity
      (fermentation potency) exceeded 7.5 x 10(6) IU/mL, which was the highest among
      those of all kinds of recombinant strains reported now.

PMID- 16108496
TI  - [Physical and chemical characters of recombinant human nucleoside diphosphate
      kinase A].
AB  - To purify recombinant human nucleoside diphosphate kinase A (rhNDPK-A) and
      determine its physical and chemical characters, recombinant NDPK-A producing E.
      coli was cultured in 80L fermentor under high cell density culture (HCDC)
      conditions. The harvested cells were treated with high pressure to break the cell
      up, tangential-flow microfiltration to remove the bacteria debris and
      ultrafiltration to concentrate the filtered solution containing target protein.
      The crude NDPK-A was purified by ion exchange chromatography with DEAE Sepharose
      Fast Flow, affinity chromatography with Cibarcron Blue 3GA Sepharose CL-4B and
      gel filtration with Sephadex G-100. The purity of rhNDPK-A was analyzed with SDS
      PAGE and RP-HPLC. The Enzymatic activity was determined with RP-HPLC. The
      molecular weight (MW) was measured with matrix assisted laser desorption
      ionization time-of-flight MS (MALDI-TOF MS). The N-terminal residue was sequenced
      with Edman method. The apparent molecular weight of rhNDPK-A in solution was
      determined with multiangle laser light-scattering method (MALS). It was found
      that the purity of rhNDPK-A was 97.3% with SDS-PAGE method and 99.2% with RP-HPLC
      method. The specific enzymatic activity was (900 +/- 100) u/mg. The molecular
      weight was 17017, which was 132 less than the calculated value according to the
      amino acid sequence of NDPK-A. The sequencing result of rhNDPK-A revealed that
      its N-terminal residue was Ala, which was the second residue on N-terminal of
      native NDPK-A. The calculated MW of N-terminal deleted rhNDPK-A was 17017,
      exactly equal to the experimental value. The result of apparent MW determination
      revealed that rhNDPK-A formed homohexamer in solution with a MW of 102kD. These
      results suggested that rhNDPK-A possessed character identical to its native
      counterpart of assembling into hexamer. Confirming the identity of rhNDPK-A to
      its native counterpart provided a good foundation for drug development and
      mechanism study of NDPK-A.

PMID- 16108497
TI  - [Interface domain of hepatitis E virus capsid protein homodimer].
AB  - Hepatitis E is a main cause of acute viral hepatitis in developing countries
      where it occurs as sporadic cases and in epidemics form. The causative agent,
      hepatitis E virus, is transmitted primarily by the fecal-oral route. The
      approximately 7.5 kb positive-sense single-strand RNA genome includes three open
      reading frames (ORFs), one of which (ORF2) is postulated to encode the major
      viral capsid protein (pORF2) of 660 amino acid residues. We earlier showed that a
      bacterially expressed peptide, designated as NE2, located from amino acid
      residues 394 to 606 of ORF2, was found to aggregate into homodimer to at least
      hexamer. To understand the interface domains within this peptide vital for
      dimerization and formation of major neutralizing epitopes, NE2 protein underwent
      terminal-truncated and site-directed mutation. The hydrophobic region, ORF2 aa597
      aa602 (AVAVLA), played a key role in oligomerization. Any amino acid residue of
      this region replaced with glutamic acid residue, the peptide can not refold as
      homodimer and/or oligomer. The immunoreactivities of these mutant peptides,
      blotted with anti-HEV neutralizing monoclonal antibody (8C11) and convalescent
      human sera, show associated to the formation of homodimer. The intermolecular
      contact region on homodimer was investigated by chemical cross-linking of two
      site-directed cysteines. When the alanine on aa597 site mutated with cysteine,
      two different homodimers were found in SDS-PAGE analysis. One (42kD) can be
      disassociated with 8mol/L urea, which is postulated to form by virtue of
      hydrophobic interaction, and the other (60kD) falls apart with the reductant DTT
      present. The exact conformation, generating the cross-linking reaction of
      cysteines, was further investigated by induced-oxidation on monomer and
      hydrophobic homodimer of A597C protein with GSH/GSSG. And the results revealed,
      it is the conformation of hydrophobic homodimer that induces the disulfide bond
      come into being, instead of the one of monomer. So the aa597 site was verified to
      be located on interface domain of hydrophobically interacting homodimeric
      complex. To evaluate the biological significance of hydrophobicity of interface
      domain, we searched natural variations as to the region on all available
      databases with NCBI blast program. All variations on these amino acid residues
      kept higher hydrophobicity, which suggests that the hydrophobic domain is
      critical for the assemblage and propagation of HEV. NE2 N-terminal deletions up
      to aa458 had no effect on dimerization and took no exact part in formation of
      major neutralizing epitopes, but the fragment may act as helper for the formation
      of major neutralizing epitopes on NE2. Interestingly, the C-terminus aa605-aa660
      of ORF2 can also act as helper instead of the N-terminus of NE2. This study
      suggests an interface domain of NE2 might be vital for HEV capsomer assembly and
      formation of major neutralizing epitopes. These results may offer clues to the
      rational design of recombinant anti-HEV vaccine.

PMID- 16108498
TI  - [Cloning of human beta-microglobulin gene and its high expression in Escherichia
      coli].
AB  - Human beta2-microglobulin (beta2m) is the light chain of major histocompatibility
      complex (MHC) class I molecule. High-yield production of this protein is a
      prerequisite to the preparation of MHC I tetramer. The present study aims to
      obtain recombinant human beta2m expressed in Escherichia coli (E. coli), for the
      purpose of preparing MHC class I tetramers. For cloning of human beta2m gene, a
      pair of specific primers was designed based on the published sequence of this
      gene and the cDNA of full coding region for beta2m precursor was obtained by RT
      PCR from the total RNA of human leukocytes. The amplified cDNA was subsequently
      cloned and its sequence was confirmed by DNA sequencing analysis (the sequence
      has been deposited in GenBank with accession number of AY187687). The prokaryotic
      expression vector containing a gene encoding mature beta2m was constructed by
      inserting the DNA fragment, which was generated by PCR reaction with the cloned
      beta2m gene as template, into an IPTG-inducible expression vector pET-3c plasmid.
      The first eight codons for N terminal amino acid residues of beta2m were
      optimized for its expression in E. coli. The complete sequence of beta2 m gene in
      the expression vector was verified by DNA sequencing analysis. High-yield
      expression of beta2m was achieved in E. coli transformed with the expression
      vector, and most of the recombinant beta2m existed in the inclusion body after
      IPTG induction. The inclusion body was washed extensively and beta2m in the
      inclusion body was solublized with 8 mol/L urea. The beta2m was refolded by
      dialysis and purified by ion-exchange chromatography (Q-Sepharose). Western
      blotting assay indicated that the polyclonal antibody against human native beta2m
      could react specifically with the recombinant protein. The purified protein
      appeared as a single band on both SDS-PAGE and Western blotting, indicating that
      it was chemical and antigenic pure. This work establishes a convenient approach
      for renaturation and purification of large quantity of recombinant beta2m which
      is identical to the native protein without any tags fused except for a methionine
      residue at the amino terminus. This provides the basis for the preparation of MHC
      tetramers.

PMID- 16108499
TI  - [Participation of ions and solutes on the thermostability of alpha-amylase].
AB  - Supplement effects of ions, sugars, and amino acids on the thermostability of
      liquefying type alpha-amylase from Bacillus subtilis were examined. The addition
      of 1 mmol/L Ca2+ or about 50 mmol/L Na+ remarkably stimulated the thermostability
      of this enzyme among ions examined. The thermostability of the enzyme was
      enhanced and reduced by the extrinsic addition of 50 mmol/L acidic amino acid
      such as glutamic acid and alkaline amino acid of the concentrations of sugars
      from 0 to 1000 mmol/L the thermostability of alpha-amylase increased almost such
      as arginine, respectively. With the increases linearly. By the co-existence of
      Na+ or K+ with some amino acids or sugars the thermostability of this enzyme was
      fairly increased. The changes in the fluorescence intensity of alpha-amylase were
      examined as a function of the incubation temperature on the enzyme, which showed
      a good agreement with those of residual activities.

PMID- 16108500
TI  - [Oriented immobilization of human IgG by protein A on imaging ellipsometry
      biosensor].
AB  - The biosensor based on optical imaging ellipsometry, can be used to detect
      directly, without labeling, the surface concentration of biomolecules on solid
      surface. The feasibility of using protein A to immobilize antibody on the silicon
      surface of the imaging ellipsometry biosensor was investigated in this study. The
      results showed that the anti-IgG immobilized by the protein A on silicon surface
      could bind effectively human IgG, and the human IgG immobilized on silicon
      surface by protein A bound more polyclonal antibody molecules than that
      immobilized on silicon surface directly, suggesting that protein A might block
      the surface to prevent the absorption of human IgG on surface directly, which
      might compromise its native configuration. The silicon surface modified with
      protein A is expected to be used to immobilize a variety of antibodies, as
      protein A can bind selectively the Fc regions of many mammalian IgG. The
      combination of imaging ellipsometry and the protein A surface modification has
      the potential to be developed into immunoassays of high sensitivity.

PMID- 16108501
TI  - [Addition of TCA cycle intermediates enhances pyruvate production].
AB  - The capability of utilizing the intermediates of TCA-cycle as the sole carbon
      source by the multi-vitamin auxotrophic yeast Torulopsis glabrata CCTCC M202019
      under the conditions of vitamins limitation was demonstrated. Furthermore, the
      colony numbers grown on medium supplemented with glucose, acetate and one of the
      intermediates of TCA-cycle was higher than that of medium used glucose and
      acetate or medium used one of the intermediates of TCA-cycle carbon source. Among
      the intermediates of TCA-cycle used in this study, oxaloacetate was the best
      carbon source for the yeast and it was found that its presence stimulated the
      conversion of acetate to acetyl-CoA. In batch fermentation with glucose medium,
      the addition of 10 g/L of oxaloacetate improved the dry cell weight from 11.8 g/L
      to 13.6 g/L, and the productivity of pyruvate from 0.96 g x L(-1) x h(-1) to 1.19
      g x L(-1) x h(-1), a 24% increase after 56 h growth. The yield of pyruvate on
      glucose was also improved as well, from 0.63 g/g to 0.66 g/g.

PMID- 16108502
TI  - [Transgenic maize plants with low copy number of foreign genes were produced with
      maize Ubi-1 promoter].
AB  - Direct DNA delivery procedures (include biolistics method) often resulted in
      multiple copies of the transgenes in transformants and certain copies of them
      were rearranged. Integration of multiple copies of the introduced genes was the
      main reason of gene silencing which meant inhibition or loss of foreign gene
      expression in filial generations of transformants. In the present work, we
      compared the influences of maize Ubi-1 promoter and other promoters on copy
      number of transgenes in maize transgenic plants. Immature embryos from Zea mays
      L. plants of sib-pollinated of A188 x H99 genotype were used as initial
      materials. Type- I embryonic calluses derived from preculture of immature embryos
      were treated on N6 medium containing 0.6 mol/L sucrose for 3 approximately 5
      hours and transformed via particle bombardment with PDS1000/He delivery system
      (Bio-Rad). Bombarded calluses were treated with hyperosmotic N6 medium for 16
      approximately 20 hours continuously. Then the cultures were transferred onto
      normal N6 medium and incubated at 26 degrees C in dark for two weeks and
      subsequently selected on N6 medium supplemented with 2 or 5 mg/L phosphinothricin
      (PPT) but without casamino acid for another two weeks. The calluses after
      selective culture were transferred onto hormone-free MS medium containing 2 or 5
      mg/L PPT but without casamino acid, and incubated at 24 degrees C under 16 h
      illumination for plant regeneration. Regenerated plantlets over 2 cm in height
      were transferred to Magenta box containing 1/2 hormone-free MS medium. Plantlets
      over 8 cm in height were transplanted to soil. After growing for one week in
      greenhouse, the plants were sprayed with 250 mg/L PPT solution. Fertile
      transgenic maize plants were regenerated and confirmed by Southern blotting and
      histochemical localization of beta-glucuronidase (GUS) activity. Relations
      between promoter and copy number of transgenes in transformants were analyzed.
      Maize transgenic plants possessing an intact copy and another incomplete copy of
      beta-glucuronidase gene (gus) were obtained in case gus gene under the control of
      maize Ubi-1 promoter (pUbi:GUS). Simultaneously the co-transformed
      phosphinothricin acetyltransferase gene (bar) controlled by CaMV 35S promoter in
      another plasmid (p35S:BAR) also existed with only one copy. When pDB1 and
      (pUbi:in2) were cobombarded, the regenerated transgenic maize plant exhibited
      with only one copy of in2 gene too. It suggested that the copy number of
      transgenes in maize transformants was low if the transgenes controlled by maize
      Ubi-1 promoter. The possible reason might be that the foreign genes were
      integrated site-specifically via homologous recombination between Ubi-1 promoter
      and its endogenous sequences in maize genome, and two cotransformed plasmids had
      reconstructed as one intact molecule before integrating into maize chromosome. On
      the contrary, if p35S:BAR was cobom-barded with plasmid pAct:In1 containing rice
      Act-1 promoter (without maize Ubi-1 promoter), the transgenic maize plants had 4
      approximately 8 copies of bar gene. These results reflected that utilization of
      self gene promoter could reduce the copy number of the transgenes in transgenic
      plants of certain species itself and avoid the occurrence of gene silencing. T2
      seeds have been harvested.

PMID- 16108503
TI  - [Fermentation, purification and identification of recombinant RGD-Hirudin].
AB  - Recombinant RGD-Hirudin ( r-RGD-Hirudin ) has double functions: anti-thrombin
      activity and anti-platelet aggregation activity. To identify these functions, the
      expression plasmid, RGD-Hirudin-pPIC9K, was constructed by inserting cDNA of RGD
      hirudin in yeast expression vector pPIC9K. The high expression clone was gained
      after screening. This clone was fermented for 3 days. The r-RGD-hirudin was
      secreted into the culture. It was ultra-filtrated from culture supernatant, then
      after gel filtration chromatography and anion exchange chromatography, the
      purified r-RGD-hirudin was gained. Its purity was larger than 97% and its
      specific activity was 12 000 ATU/mg. The yield per liter culture of purified r
      RGD-hirudin was 1 g and overall recovery yield was more than 75% . The purified r
      RGD-hirudin was identified by reductive SDS-PAGE, anti-thrombin activity assay,
      anti-platelet aggregation assay, LC/MS and isoelectrofocusing assay. It is proved
      that r-RGD-Hirudin is ramification of wt-Hirudin and it has anti-thrombin
      activity and anti-platelet aggregation activity.

PMID- 16108504
TI  - [Expressing of N gene encoding nucleocapsid protein of vesicular stomatitis virus
      and elementary application in ELISA].
AB  - The gene encoding the nucleocapsid (N) protein of vesicular stomatitis virus (VSV
      NJ) was subcloned from pMD-VN5, and inserted into pBAD/Thio TOPO vector. The
      recombinant plasmid was identified by restriction analysis and PCR. It was
      sequenced to confirm the correct sequences and the correct junctional
      orientations of the inserted N gene. The results of SDS-PAGE and Western
      immunoblotting revealed that the N protein was expressed in Escherichia coli
      LGM194 in a high level and the recombinant fusion protein, which contained a N
      terminal HP-Thioredoxin and a C-terminal polyhistidine tag. It had a molecular
      mass of approximately 63.5 kD and immunologically reactive activity. The
      recombinant protein was characterized and tested in an enzyme-linked
      immunosorbent assay (ELISA) format for potential application in the serodiagnosis
      of vesicular stomatitis using 186 serum samples from experimentally infected
      goats and guinea-pigs with VSV-NJ and VSV-IN, and from field origin and reference
      serum samples. The sensitivity and specificity of the ELISA were compared with
      those of the standard microtiter serum neutralization (MTSN) tests. The ELISA and
      MTSN test results were highly correlated for detection of VSV antibodies. The
      ELISA was as sensitive as the SN assay in detecting positive serum to VSV. The
      correlation between SN titers and ELISA titers was statistically significant.
      These data suggest that the recombinant fusion N protein of VSV could be used as
      a recombinant test antigen for the serodiagnosis of vesicular stomatitis. The
      ELISA based on the reconmbinant nucleocapsid protein may offer the best
      combination of rapidity, sensitivity, simplicity, economy, and laboratory
      biosafety of any of the methods yet developed for VSV serodiagnosis. This study
      lay on foundation for the development of the diagnosis methods in serology for
      VSV.

PMID- 16108505
TI  - [Construction of recombinant fowlpox virus expressing chicken IL-2 and assay of
      biologic activity of the product in vitro].
AB  - In order to determine the adjuvant effects of the chicken IL-2 (ChIL-2) on new
      generation vaccines, ChIL-2 gene was amplified from ConA-stimulated chicken
      spleen cells by RT-PCR and was directionally inserted into fowlpox virus (FPV)
      transferring vector p1175 under the control of FPV early/late promoter (PE/L),
      resulting in recombinant transferring vector p1175IL2. Then the p1175IL2 plasmid
      was transfected into chicken embryo fibroblasts (CEF) pre-infected with wild type
      FPV to generate recombinant fowlpox virus expressing ChIL-2 (rFPV-IL2). By
      selection of blue plaques on the CEF, overlaid with agar containing X-gal, rFPV
      IL2 was obtained and purified. The supernatant from CEF monolayer infected with
      rFPV-IL2 (M.O.I2.0) after 72 hours was detected for the production of ChIL-2 by
      XTT/PMS colorimetric assay. About 3.6 x 10(5) u/mL of specific ChIL-2 activity
      was determined. The results show that rFPV-IL2 can express ChIL-2 effectively.
      rFPV-IL2 provides us with an effective tool for studying avian immunology as well
      as a potential vaccine-enhancing agent.

PMID- 16108506
TI  - Abortion: a major contributor to maternal ill health.

PMID- 16108507
TI  - Phloroglucinol for acceleration of labour: double blind, randomized controlled
      trial.
AB  - OBJECTIVES: To determine the effects of Phloroglucinol in acceleration of labour
      and its adverse effects on mother and foetus. METHODS: A double blind randomized,
      placebo controlled trial was conducted on 100 patients in active phase of
      uncomplicated labour selected by convenient sampling. Patients were given
      Phloroglucinol or Placebo (distilled water) intravenously. Progress of labour was
      plotted on Partogram. Any adverse effects of the drug on mother and fetus were
      noted. Student's t-test was applied for statistical analysis. RESULTS: In
      patients receiving Phloroglucinol there was a mean 34% reduction in duration of
      1st stage of labour and a mean 23% reduction in 2nd stage as compared to Placebo
      group respectively. Blood loss >500ml was observed in 2% patients. Otherwise
      there were no adverse effects on mother or foetus. CONCLUSION: Phloroglucinol
      shortens the duration of labour, is non toxic to both mother and fetus and does
      not cause primary post partum haemorrhage.

PMID- 16108508
TI  - Epidemic adenoviral conjunctivitis report of an outbreak in a military garrison
      and recommendations for its management and prevention.
AB  - OBJECTIVE: The study was conducted to document the cases of adenoviral
      conjunctivitis, evaluate its clinical patterns, prevent its transmission and
      reduce its severity and complications during an epidemic. METHODS: A total of
      2968 cases of adenoviral conjunctivitis were documented during the months of
      June, July and August 2003. By simple randomization, 200 Patients were selected
      and divided into two groups on the basis of treatment. Group 1 (Treatment group)
      40% patients were given topical anti-histamine/decongestant eye drops whereas
      Group 2 (Control group) 60% patients were managed conservatively by washing eyes
      with cold water and applying ice packs on the eyes. RESULTS: Highest incidence of
      the disease was seen in the month of July 2003. In most of cases (90%) both eyes
      of the respondents were affected. Acute illness lasted from 4.91 days in Group 1
      and 7.86 days in Group 2. Commonly observed symptoms included redness, watering,
      itching, burning, pain in the eyes and photophobia. Duration of the illness was
      less and severity was mild in Group 1 patients as compared with Group 2 patients
      this was found to be statistically significant using T test (P< 0.05). None of
      the cases reported any complication after complete recovery from adenoviral
      conjunctivitis. CONCLUSION: Adenoviral conjunctivitis is a highly contagious
      disease and often spreads in epidemics, particularly in crowded communities with
      poor hygiene. Prevention of transmission is the most important therapeutic
      measure particularly in the ophthalmic clinics of the hospitals. Although the
      disease is benign and self-limiting, cold compresses and topical anti
      histamine/decongestant eye drops reduce the discomfort and severity of the
      disease.

PMID- 16108509
TI  - Proportion of gastroesophageal reflux symptoms in patients with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: To determine the proportion of gastroesophageal reflux symptoms in
      patients with chronic obstructive pulmonary disease and its association with the
      severity and worsening of the symptoms of chronic obstructive pulmonary disease
      (COPD). METHODS: A prospective, questionnaire based, case control, analytical
      study was conducted in the Department of Pulmonology, Jinnah Postgraduate Medical
      Centre, Karachi during June 2002 to January 2005. Gastroesophageal reflux
      symptoms were compared between 100 chronic obstructive pulmonary disease patients
      who fulfilled the inclusion criteria and 150 control subjects. Both groups were
      interviewed according to modified version of Mayo clinic GER questionnaire.
      Chronic obstructive pulmonary disease patients were divided into two groups
      according to pulmonary function tests (PFTs) results into FEV1 <50% and FEV1
      >50%. RESULTS: Chronic obstructive pulmonary disease patients had more frequent
      gastroesophageal symptoms than controls (25% vs. 9.33% respectively; p=0.001),
      heartburn/acid regurgitation (70% vs. 43.33% and 56% vs. 30.66% respectively; p
      value=0.001), dysphagia (15% vs. 4%; p-value=0.002) and chronic cough (89% vs.
      29.33%; p-value=0.001). Twenty six COPD patients reported respiratory symptoms
      associated with reflux, whereas control subjects denied such association. Of the
      11 patients with frequent gastroesophageal symptoms, 10 patients increased their
      inhaler use (p=0.001). Frequent gastroesophageal symptoms had shown a significant
      association with decreased FEV1 (25 % vs. 0% p-value 0.001). In contrast
      Pulmonary function test results were similar among chronic obstructive pulmonary
      disease patients with and without gastroesophageal symptoms (48.13+20.81 vs.
      50.94+23.33). Anti-reflux medication proton pump inhibitor and H2-blockers were
      utilized more by COPD patients as compared to control subjects. CONCLUSION: A
      higher proportion of frequent gastroesophageal symptoms were noted by COPD
      patients than control subjects and higher proportion of gastroesophageal symptoms
      was present in severe COPD patients.

PMID- 16108510
TI  - Surgical management of genitourinary fistula.
AB  - OBJECTIVE: To determine the commonest cause of genitourinary fistulae and
      evaluate the experience of the surgical management. The study was carried out at
      the Urology Department, Jinnah Postgraduate Medical Centre (JPMC), Karachi.
      METHODS: Twenty two patients were operated including 14 of Vesicovaginal Fistula
      (WF), and 8 of Ureterovaginal Fistula (UVF). In one patient of WF fistula was
      extending up to proximal urethra. Out of 14 WF cases, 9 patients underwent
      transvaginal repairs, 1 extraperitoneal transvesical repair and 1 transperitoneal
      repair. Three urinary diversions including 1 Mitrofanoff and 2 ileal conduits
      were also made. Ureteroneocystostomy was done in cases of UVF with adjuvant
      procedures in 3 cases including Psoas Hitch in 1 and Boari's flap in 2 patients.
      RESULTS: The mean age was 35 (range 21-50) years. WF due to obstetric causes was
      seen in 71.4% patients while 28.6% developed WF secondary to gynaecological
      procedures. Majority of (91%) WF were repaired successfully in the first attempt
      in patients subjected to the procedure (78.6% cases of WF). There was only one
      recurrence in transvaginal repair, which was successfully treated with
      extraperitoneal transvesical approach in second attempt, thus augmenting the
      success rate to 100%. However 3 (21.4%) cases of WF required urinary diversion as
      there was complete loss of sphincter mechanism in one case, in which fistula was
      extending up to the urethra, and in two cases of complex WF with complete loss of
      posterior bladder wall surrounded by extensive scarring. All cases of UVF were
      successfully treated with ureteroneocystostomy alone or with adjuvant procedure
      in 37.5% cases. CONCLUSION: Uncomplicated WF can be successful repaired
      transvaginally by refreshing the fistulous edges without excising it.
      Transabdominal route should be reserved for complicated WF. Ureteroneocystostomy
      with antireflux mechanism with or without adjuvant procedure is the treatment of
      choice for UVF resulting from complete transaction or ligation of ureter.

PMID- 16108511
TI  - Knowledge of students regarding hepatitis and HIV/AIDS of a private medical
      university in Karachi.
AB  - OBJECTIVE: To determine and assess the level of awareness among students of a
      private medical college regarding HIV/AIDS, Hepatitis B and C. METHODS: A survey
      was conducted to assess the awareness of medical students on HIV/AIDS, hepatitis
      B and C. They were asked to fulfill a pre-tested structured questionnaire. The
      variables accessed were their knowledge of disease regarding etiology, mode of
      transmission, and prevention. RESULTS: A total of 267 students participated, with
      117 (43.8%) students from pre-clinical years and 150 (56.2%) from the clinical
      years. The male female ratio was 1:2, mean age of respondents was 21 +/- 1.5
      years. Majority of the students (98%) agreed that an infected person is a major
      source of transmitting these infections. Almost all (95%) students knew that
      blood transfusion was an important source of transmitting these infections.
      Wearing gloves (87%) and safe disposal of sharps waste (98%) were known by the
      students to be the ways to protect against these infections. A significant
      difference was noted on comparing the knowledge between preclinical and clinical
      students regarding medical / surgical procedures causing these infections
      (p<0.001) and also regarding the ways to protect against these diseases
      (p=0.001). CONCLUSION: There is a lack of awareness among the medical students
      entering into the profession. It is the need of the hour to emphasize on
      practicing universal precautions. In addition, some preventive measures should be
      taken by the management of the universities and medical students to avoid the
      occurrence of these problems.

PMID- 16108512
TI  - The quest for small family size among Pakistani women--is voluntary termination
      of pregnancy a matter of choice or necessity?
AB  - OBJECTIVE: To present the socio-biologic predictors of induced abortion among
      married women residing in low income squatter settlements of Karachi, Pakistan.
      METHODS: A cross-sectional survey was conducted in three squatter settlements of
      Karachi from June to August 1997. Interviews were conducted on 1,214 married
      women assessing past pregnancy history, literacy and employment status of self
      and spouse and specifically probing for past history of seeking an induced
      abortion. RESULTS: Fifty women reported an induced abortion during last three
      years prior to survey. Of these, forty percent (20/50) of abortion seekers were
      using some method of family planning before conceiving the index pregnancy. Post
      abortion family planning method use was adopted by 50% (25/50) of the abortion
      seekers. The most parsimonious multivariate logistic regression model included
      grand-multigravidity (OR 2.6 CI, 1.3 - 5.2), literate status of the woman (OR 1.9
      CI, 1.0 - 3.4) and the 26-35 age group (OR 3.0 CI, 1.4 - 6.6). CONCLUSIONS:
      Unplanned/mistimed pregnancies generally result from high unmet need and
      ineffective use of contraceptives and culminate through induced abortions. We
      propose that improvement in the quality of family planning counseling should be
      targeted to effective use of a method, back-up support in case of method failure
      and the health consequences of unsafe abortions.

PMID- 16108513
TI  - Trans-vaginal sonographic evaluation of vesicovaginal fistula.
AB  - OBJECTIVE: To determine the sensitivity of transvaginal ultrasound (TVUS) in the
      detection of vesicovaginal fistula (VVF). METHODS: The study included 15 patients
      with urinary incontinence suspected or diagnosed to be due to vesicovaginal
      fistula that were originally referred to the department for intravenous urography
      (IVU). Complimentary TVS was done with consent. Cases with stress incontinence
      and co-existent rectovaginal fistulae were excluded. Findings were compared
      against the cystogram, cystoscopy and surgical findings for determining the
      sensitivity, the last being taken as the gold standard. RESULTS: The fistula was
      visualized as a jet of echoes in real time from bladder to the vagina in all 15
      cases. The location number and size corresponded with the surgical findings. The
      sensitivity of trans-vaginal scanning in diagnosing WF was 100%, that of
      cystoscopy- 93% and of cystography- 60%. CONCLUSION: In this series, the trans
      vaginal scan findings correlated well with the surgical findings. It was less
      invasive and more tolerable than cystoscopy.

PMID- 16108514
TI  - Stalling HIV through social marketing: prospects in Pakistan.
AB  - Over the last two decades HIV/AIDS has evolved from a series of interesting case
      reports to a growing epidemic that threatens the entire world. It is feared to
      cause devastation among large pockets of populations and may roll back more than
      thirty years of public health achievements. This killer disease has been more
      amenable to behavioral change than by provision of curative services and attempts
      are being made to educate the public about this threat. Various techniques of
      promotion have been tried through out the world including television
      dramas/soaps, mass media and school curricula. Social marketing is an evolving
      strategy used to influence human behavior and choices. By using the principles of
      marketing and promoting behavior as a product, social marketers attempt to
      understand the dynamics of human behaviour and devise messages and products to
      change, modify, accept or reject unsafe behaviors or practices. Thus, social
      marketers provide an effective force to combat the spread of HIV and may serve to
      be invaluable allies in health promotion efforts. In a complex and diversified
      cultural milieu of Pakistan, social marketing can have a significant impact on
      health determinants and the conditions that will facilitate the adoption of
      health-oriented behaviors and practices. This paper gives an account of the
      elements needed for the success of a health promotion strategy adopted in a
      developing country and makes a case for social marketing to be adopted as the
      lead strategy for stalling HIV/AIDS in Pakistan.

PMID- 16108515
TI  - Ampullary ganglioneuroma: an unusual feature of neurofibromatosis type 1--a case
      report.
AB  - The case of a 65 year old man is presented. He had a history of dyspepsia and was
      diagnosed as neurofibromatosis clinically. Upper G.I. endoscopy showed thickened
      folds in duodenum. A polyp was seen at the junction of D1 and D2 adjacent to the
      ampulla. Duodenal biopsy results were suggestive of ganglioneuroma.

PMID- 16108516
TI  - Rapidly developing optic neuritis secondary to ethambutol: possible mechanism of
      injury.
AB  - Optic neuritis has been described among the toxic effects of Ethambutol. This
      side effect is dose related. The mean duration of Ethambutol induced optic
      neuritis (EON) is three months. We report a case of EON after few days of
      exposure to Ethambutol and the symptoms resolved after discontinuation of
      Ethambutol. This most likely represents an idiosyncratic reaction which is
      different as compared to dose related optic neuritis.

PMID- 16108518
TI  - Transfusion related acute lung injury.
AB  - TRALI (Transfusion related acute lung injury) is a devastating complication of
      Blood transfusions or its components irrespective of the blood grouping and cross
      match, We report a case of a Philipino house wife who had blood transfusion for
      her vaginal lacerations and developed acute pulmonary edema immediately
      afterwards. Antigranulocyte antibodies were not found in the donors. The patient
      recovered after supportive treatment. TRALI is not an uncommon complication of
      Blood transfusion that is under-reported and under-diagnosed.

PMID- 16108519
TI  - Pulmonary embolism in pemphigus vulgaris, the need for judicious immunotherapy.
AB  - Pemphigus vulgaris is a serious chronic mucocutaneous ailment. In recent decades
      advances in diagnostic and therapeutic measures have led to a significant decline
      in morbidity and mortality. However, with the advent of active and prolonged
      immunotherapy involving corticosteroids, there has been a rise in steroid
      associated complications. This has led to significant concern globally over the
      sensible use of treatment regimen in pemphigus patients. We present a patient who
      underwent a massive pulmonary embolism following over usage of corticosteroid
      therapy for pemphigus vulgaris. Whilst the patient survived owing to timely
      assessment and aggressive surgical intervention, the need for cautious and
      judicious immunotherapy in pemphigus is emphasized.

PMID- 16108520
TI  - Detection of acute Helicobacter pylori infection using serological antibody
      assay.

PMID- 16108517
TI  - Emergence of metallo-beta-lactamase producing Pseudomonas aeruginosa in Pakistan.
AB  - We report a case of urinary tract infection due to metallo-beta-lactamase
      producing Pseudomonas aeruginosa resistant to carbapenems. This report signals an
      ominous development. Unless curbed by judicious use of antibiotics and early
      detection by screening tests, spread of this plasmid-mediated resistance can
      render the carbapenems ineffective.

PMID- 16108521
TI  - Rationale for using Peltophorum africanum (Fabaceae) extracts in veterinary
      medicine.
AB  - Peltophorum africanum (Fabaceae) is a deciduous tree widespread in southern
      Africa. The plant has many ethnomedical and ethnoveterinary uses. Root and bark
      decoctions are used to treat diarrhoea, dysentery, sore throat, wounds, back and
      joint pains, HIV-AIDS, venereal diseases and infertility. Pastoralists and rural
      farmers use the root and bark extracts to treat diarrhoea, dysentery,
      infertility, and to promote well-being and resistance to diseases in cattle. To
      evaluate these ethnobotanical leads, dried leaves, stem bark and root bark were
      extracted with ethanol, acetone, dichloromethane and hexane. Polyphenols in the
      extract were determined by the Folin-Ciocalteu method with gallic acid as
      standard. Qualitative antioxidant activity was screened by spraying thin layer
      chromatograms (TLC) of the extracts with 0.2% 1,1-diphenyl-2-picryl hydrazyl
      (DPPH), and quantified with Trolox equivalent antioxidant capacity (TEAC) assay.
      Minimum inhibitory concentration (MIC) and total antibacterial activity (TAA)
      were determined by serial microplate dilution for Staphylococcus aureus,
      Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis, with
      gentamicin as standard and tetrazolium violet as growth indicator. Acetone and
      ethanol extracted the largest quantity of material. Polyphenols concentration was
      49.2% in acetone extract of the root and 3.8% in dichloromethane extract of the
      leaf. Antioxidant activity of at least 5 antioxidant compounds as measured by
      TEAC ranged from 1.34 (ethanol extract of the root) to 0.01 (hexane extract of
      the leaf). The total antibacterial activity (volume to which active compounds
      present in 1 g plant material can be diluted and still inhibit bacterial growth)
      was 1263 ml/g for ethanol extract of the root against S. aureus, and 800 ml/g for
      acetone extract of the root against P. aeruginosa. There was substantial activity
      against both Gram-positive and Gram-negative bacteria, with MIC values of 0.08
      mg/ml for S. aureus and 0.16 mg/ml for P. aeruginosa. There is therefore a
      rationale for the traditional use of root and bark of P. africanum in treating
      bacterial infection related diseases.

PMID- 16108522
TI  - Canine cutaneous neoplasms: prevalence and influence of age, sex and site on the
      presence and potential malignancy of cutaneous neoplasms in dogs from Zimbabwe.
AB  - Histopathological examination was performed on cutaneous biopsies from 900 dogs
      with skin lesions from Zimbabwe, collected from 1996 to 2000. Clinical data were
      collected from medical records. Sixty per cent (540/900) of the cases were
      tumours and 40% (360/900) were non-neoplastic inflammatory or degenerative
      diseases. Thirty different histological types of tumour were diagnosed. The
      prevalence of epithelial, mesenchymal, lymphohistiocytic and melanocytic tumours
      was 39.4%, 44.4%, 7.4% and 8.7%, respectively. The 10 most common tumours,
      comprising 73.7% of all cutaneous neoplasms, were mast cell tumours, squamous
      cell carcinomas, perianal gland adenomas, lymphomas, benign melanomas,
      haemangiosarcomas, sebaceous gland adenomas, fibrosarcomas, lipomas and malignant
      melanomas. The prevalence of various neoplasms, age of affected dogs and sites of
      occurrence were similar to surveys in other countries, except that in Zimbabwe
      there was a greater prevalence of lymphomas and of tumours associated with
      increased exposure to ultraviolet light (squamous cell carcinomas,
      haemangiosarcomas and melanomas). For all classes of tumours the sex of the dog
      did not have any significant influence on the likelihood of developing a tumour.
      For a dog diagnosed with a tumour located on the trunk, the tumour was
      significantly more likely to be an epithelial tumour than a non-epithelial tumour
      The occurrence of melanocytic tumours on the trunk was significantly lower than
      at other sites. Lymphohistiocytic tumours were 10 times more likely to occur at
      multiple locations as opposed to single locations.

PMID- 16108523
TI  - The possible role of Ostertagia circumcincta, coccidiosis and dietary protein
      level in the development of swelling disease in Angora goat kids.
AB  - A trial was carried out to investigate the possible role of Ostertagia
      circumcincta, coccidiosis and level of protein in the diet in the development of
      swelling disease in Angora goat kids. Eighty Angora goat kids were bought from 5
      producers whose flocks had a history of swelling disease. These kids were kept in
      enclosures at Grootfontein Agricultural Development Institute near Middelburg
      (Eastern Cape) for the duration of the experiment. The animals received a
      combination of the following treatments: (a) high protein vs normal protein diet;
      (b) Ostertagia circumcincta infection or no O. circumcincta infection; (c)
      coccidial infection or no coccidial infection. Data recorded included weekly body
      weight, weekly total plasma protein levels (TPP), weekly faecal egg counts,
      weekly coccidial oocyst counts and haematology at Weeks 1, 5, 9, 13 and 16. The
      goats were also monitored daily for any clinical symptoms. There was no specific
      trend in any of the parameters measured among the different treatment groups at
      any stage during the experimental period. The goats were shorn during Week 10 of
      the experiment. On Monday 6 September 2004 (Week 12 of the study), 19 of the
      goats developed some subcutaneous oedema. The Saturday (4 September 2004) was
      rather hot (30 degrees C), followed by very cold rainy conditions (11 degrees C)
      on Sunday (5 September 2004). Twelve of the goats developed what can be described
      as little oedema, while 7 developed moderate oedema. The number of goats that
      developed oedema was fairly evenly distributed among the various treatment
      groups. As far as the specific treatments are concerned, more goats on the normal
      protein diet developed moderate oedema than the goats on the high protein diet.
      Body weights of goats that developed moderate oedema were lower throughout the
      experimental period than body weights of goats that developed little or no
      oedema, while TPP of goats that developed moderate oedema were lower from Week 5
      of the study onwards. There were also no significant differences at any stage
      throughout the experimental period in faecal egg counts, faecal coccidial oocyst
      counts or any of the blood parameters between goats that developed moderate
      oedema, little oedema and those that did not develop any oedema. No goats
      developed full-blown swelling disease during the course of the experiment. It is
      possible that the treatments applied in this study are not inductive of the
      disease, or the effects of the treatments were not severe enough to induce
      swelling disease.

PMID- 16108524
TI  - Microbiological quality of goat's milk obtained under different production
      systems.
AB  - In order to determine the safety of milk produced by smallholder dairy goat
      farms, a farm-based research study was conducted on commercial dairy goat farms
      to compare the microbiological quality of milk produced using 3 different types
      of dairy goat production systems (intensive, semi-intensive and extensive). A
      survey of dairy goat farms in and around Pretoria carried out by means of a
      questionnaire revealed that most of the smallholder dairy goat farms surveyed
      used an extensive type of production system. The method of milking varied with
      the type of production system, i.e. machine milking; bucket system machine
      milking and hand-milking, respectively. Udder half milk samples (n=270) were
      analysed, of which 31.1% were infected with bacteria. The lowest intra-mammary
      infection was found amongst goats in the herd under the extensive system (13.3%),
      compared with 43.3% and 36.7% infection rates under the intensive and semi
      intensive production systems, respectively. Staphylococcus intermedius (coagulase
      positive), Staphylococcus epidermidis and Staphylococcus simulans (both coagulase
      negative), were the most common cause of intramammary infection with a prevalence
      of 85.7% of the infected udder halves. The remaining 14.3% of the infection was
      due to Staphylococcus aureus. Bacteriology of bulk milk samples on the other
      hand, showed that raw milk obtained by the bucket system milking machine had the
      lowest total bacterial count (16,450 colony forming units (CFU)/ml) compared to
      that by pipeline milking machine (36,300 CFU/ml) or hand-milking (48,000 CFU/ml).
      No significant relationship was found between the somatic cell counts (SCC) and
      presence of bacterial infection in goat milk In comparison with the herds under
      the other 2 production systems, it was shown that dairy goat farming under the
      extensive production system, where hand-milking was used, can be adequate for the
      production of safe raw goat milk.

PMID- 16108525
TI  - Seasonal occurrence and production effects of the biting louse Damalinia limbata
      on Angora goats and 2 treatment options.
AB  - Adult biting lice Damalinia limbata (Gervais 1844) were most numerous on Angora
      goats in southwestern Free State Province from November to May with the smallest
      numbers present during August. Nymphs were most numerous from January to March
      with the smallest numbers present during July. The largest proportion of adult
      lice was present on the ventral surface of goats during winter, when population
      numbers were lowest, and the largest proportion of nymphs during summer, when
      population numbers were highest. Infestation did not affect the body weight of
      goats, but adversely affected both the quantity and quality of mohair produced. A
      single treatment with deltamethrin, applied as a pour-on along the mid-line of
      the backs of the goats, effectively controlled infestation and resulted in a
      significant increase in mohair production compared with untreated goats.
      Deltamethrin sprayed along the sides of the animals was equally effective in
      controlling infestation.

PMID- 16108526
TI  - Analgesic and systemic effects of xylazine, lidocaine and their combination after
      subarachnoid administration in goats.
AB  - The objective of the study was to determine the analgesic and systemic effects of
      subarachnoid administration of xylazine hydrochloride (XY), lidocaine
      hydrochloride (LI) and their combination (XYLI) in goats. Six healthy goats were
      used in a prospective randomised study. Three treatments were administered to
      each goat, with 1-week intervals between each treatment. Treatments consisted of
      0.1 mg/kg xylazine, 2.5 mg/kg lidocaine and a combination of xylazine 0.05
      (mg/kg) and lidocaine (1.25 mg/kg). Analgesia, ataxic, sedative, cardiovascular
      and respiratory effects, and rectal temperature were evaluated before (baseline)
      and at 5, 10, 15, and 30 min after subarachnoid injection, and then at 30-min
      intervals until loss of analgesia occurred. Lidocaine induced analgesia in 3.1 +/
      1 min (mean +/- SD), which lasted for 66 +/- 31 min. Heart and respiratory rates
      and blood pressure remained unchanged after lidocaine-induced analgesia. Xylazine
      induced analgesia in 9.5 +/- 2.6 min and xylazine-lidocaine in 3.2 +/- 1.2 min.
      Xylazine-lidocaine-induced analgesia lasted longer (178.3 +/- 37 min) than that
      induced by xylazine (88.3 +/- 15 min). The XYLI treatment induced prolonged motor
      blocking (115 min), more than the XY (80 min) and LI (90 min) treatments. Both
      xylazine and xylazine-lidocaine caused significant decreases in the heart and
      respiratory rates, but not in blood pressure. The combination of xylazine (0.05
      mg/kg) and lidocaine (1.25 mg/kg) can be administered subarachnoidally (between
      last lumbar vertebra and 1st sacral vertebra) to produce prolonged (> 2.5 h)
      analgesia of the tail, perineum, hind limbs, flanks and caudodorsal rib areas in
      goats. Despite the prolonged analgesia, using this combination is desirable for
      relieving postoperative pain, but it may be a disadvantage due to a motor block
      when dealing with goats.

PMID- 16108527
TI  - Inhibition of bacterial growth by different mixtures of propofol and thiopentone.
AB  - Propofol is, as a result of its formulation, an ideal bacterial and yeast culture
      medium. An outbreak of sepsis in humans and an increase in wound infections in
      dogs has been ascribed to the use of propofol. It has been previously reported
      that a 1:1 mixture of propofol and thiopentone has bactericidal properties. This
      study was undertaken to determine if further serial mixtures of propofol and
      thiopentone maintained the bactericidal properties. Mixtures of 1:1 (solution A),
      5:1 (solution B), 10:1 (solution C), 50:1 (solution D) and 100:1 (solution E) of
      1% propofol to 2.5 % thiopentone, 2.5% thiopentone (solution T), 1% propofol
      (solution P) and saline (solution S) were prepared and inoculated with between
      10(5) and 10(6) colony-forming units of Staphylococcus aureus, Escherichia coli,
      Pseudomonas aeruginosa and Candida albicans. A sample was withdrawn from each
      solution at 0, 1, 6, 12, 48 and 120 hours after inoculation and a bacterial count
      was performed. This study showed that thiopentone and solution A behaved in
      similar fashion by inhibiting bacterial growth and was bactericidal after 48
      hours. Solution B was not bactericidal against S. aureus and C. albicans.
      Propofol and solutions D and E all supported growth of all the organisms tested.
      These data indicate that mixtures of propofol and thiopentone at a ratio less
      than 1:1 do not maintain the bactericidal properties.

PMID- 16108528
TI  - Renal medullary AA amyloidosis, hepatocyte dissociation and multinucleated
      hepatocytes in a 14-year-old free-ranging lioness (Panthera leo).
AB  - A 14-year-old lioness, originating from Etosha in Namibia, and a member of a
      pride in Pilanesberg National Park since translocation in 1994, was euthanased
      due to fight-related vertebral fracture and spinal injury, incurred approximately
      6-8 weeks previously. Blood specimens collected at the time of death showed mild
      anaemia and a leukogram reflecting stress and chronic infection. Necropsy
      conducted within 2 hours of death was on a dehydrated, emaciated animal with
      hindquarter wasting and chronic traumatic friction injuries from dragging her
      hindlegs. There was cellulitis in the region of bite-wounds adjacent to the
      thoraco-lumbar vertebral fracture, at which site there was spinal cord
      compression, and there was marked intestinal helminthiasis. The outer renal
      medullae appeared pale and waxy and the liver was macroscopically unremarkable.
      Histopathology and electron microscopy of the kidneys revealed multifocal to
      coalescing deposits of proximal medullary interstitial amyloid, which fluoresced
      strongly with thioflavine T, and was sensitive to potassium permanganate
      treatment prior to Congo Red staining, thus indicating inflammatory (AA) origin.
      There was diffuse hepatocyte dissociation, as well as numerous binucleated and
      scattered multinucleated (up to 8 nuclei/cell) hepatocytes, with swollen
      hepatocyte mitochondria, in liver examined light microscopically.
      Ultrastructurally, the mono-, bi- and multinucleated hepatocytes contained
      multifocal irregular membrane-bound accumulations of finely-granular, amorphous
      material both intra-cytoplasmically and intra-nuclearly, as well as evidence of
      irreversible mitochondrial injury. The incidence and relevance in cats and other
      species of amyloidosis, particularly with renal medullary distribution, as well
      as of hepatocyte dissociation and multinucleation, as reported in selected
      literature, is briefly overviewed and their occurrence in this lioness is
      discussed.

PMID- 16108529
TI  - In vitro investigation of the toxic effects of extracts of Allium sativum bulbs
      on adults of Hyalomma marginatum rufipes and Rhipicephalus pulchellus.
AB  - The toxic effects of the extracts of Allium sativum (Garlic) were evaluated
      against adults of Hyalomma marginatum rufipes and Rhipicephalus pulchellus using
      three types (Types A, B and C) of contact toxicity bioassays. A. sativum bulbs
      were extracted with acetone, ethanol and dichloromethane (DCM) solvents. Among
      these three solvents, it is the DCM extract of A. sativum that appears to have
      anti-tick activity. In the Type A contact toxicity bioassay, DCM extracts of A.
      sativum demonstrated a high acaricidal bioactivity against H. m. rufipes with
      100% of ticks killed in less than an hour, and toxicity persisted to the second
      day. A weak acaricidal activity of aqueous extracts of A. sativum was observed in
      the Type B contact toxicity bioassay. In the Type C contact toxicity bioassay, a
      concentration of 24% w/v of DCM extracts of garlic in sunflower oil (Helianthus
      annuus) had killed 100% of H. m. rufipes (LC50 = 5.9% w/v) and R. pulchellus
      (LC50 = 10.3% w/v) by 24 hours post-treatment of ticks. The results obtained from
      this study suggest that DCM extract of A. sativum is a potential source of novel
      acaricidal agents.

PMID- 16108530
TI  - Serosurvey for canine distemper virus exposure in dogs in communal lands in
      Zimbabwe.
AB  - Sera from 173 apparently healthy, unvaccinated dogs from 4 widely separated
      communal lands in Zimbabwe were tested by ELISA for antibodies against canine
      distemper virus. Overall, 82% were positive with high prevalences found in each
      communal land. The highest seroprevalence was in dogs between 1 and 2 years of
      age (91%; 49/54). These results show dogs in the communal lands of Zimbabwe are
      commonly exposed to canine distemper virus and that a substantial number survive
      infection. The role that the virus might play in the high mortality rate of the
      dog population on communal land warrants further investigation.

PMID- 16108531
TI  - Datura contamination of hay as the suspected cause of an extensive outbreak of
      impaction colic in horses.
AB  - Datura poisoning of horses is extensively reviewed. An outbreak of intractable
      impaction colic affecting 18 of 83 horses was stopped by withdrawing dried tef
      hay contaminated with young Datura plants. The dried, botanically identified
      Datura stramonium and D. ferox contained respectively 0.15% mass/mass (m/m)
      hyoscyamine as well as 0.16% m/m hyoscine (scopolamine) and only hyoscine at a
      concentration of 0.11% m/m. Immature, unidentifiable plants resembling D.
      stramonium, contained 0.14% m/m and 0.12% m/m of the 2 respective tropane
      alkaloids. The outbreak was characterised by protracted and repeated colic
      attacks due to impaction of the large colon and/or caecum without any other anti
      muscarinic signs. Comparative analyses of single specimens of dried seed of the 2
      species collected from both fertilised and waste areas revealed that young South
      African Datura spp. had levels of tropane alkaloids comparable to those in the
      well-known toxic seed and were, consequently, equally toxic. The inherent danger
      of tef hay being contaminated with Datura is emphasised. To our knowledge this is
      the 1st field case of poisoning in horses ascribed to the vegetative parts of
      Datura spp.

PMID- 16108532
TI  - Tracheal perforation managed by temporary tracheostomy in a horse.
AB  - Tracheal trauma with resultant rupture is uncommonly reported in veterinary
      literature. We report the case of a 16-year-old Thoroughbred gelding that
      sustained a 1 cm longitudinal perforation of the dorsal tracheal membrane in the
      proximal cervical region. The horse subsequently developed dyspnoea due to acute
      upper respiratory obstruction secondary to severe emphysema of the guttural
      pouches. A temporary tracheostomy caudal to the site of tracheal perforation was
      performed under local anaesthesia. This procedure helped relieve the upper airway
      obstruction and aided resolution of the injury by diverting air away from the
      site of tracheal perforation. After conservative management, the gelding
      recovered completely.

PMID- 16108533
TI  - First report of suspected ethylene glycol poisoning in 2 dogs in South Africa.
AB  - Ethylene glycol (anti-freeze) toxicity is a serious emergency in both veterinary
      and human medicine. Ethylene glycol (E/G) is the active anti-freeze principle in
      radiator water additives. It is odourless, colourless and has a sweet taste. As
      little as 5 ml or 20 ml is sufficient to kill a cat or a dog, respectively.
      Ethylene glycol is rapidly absorbed and metabolised in the liver to oxalate,
      which is deposited as calcium oxalate in the kidneys causing irreversible damage.
      This report describes 2 dogs that were suspected to have ingested ethylene
      glycol. The report contains a description of the 3 stages of ethylene glycol
      toxicity as well as a short discussion of the treatment. Public awareness about
      the dangers of anti-freeze will help in limiting exposure of pets and humans to
      this potentially fatal toxin. Veterinarians need to be aware of anti-freeze
      toxicity as delayed recognition and treatment will lead to the death of the
      patient.

PMID- 16108534
TI  - Spinal spondylosis and acute intervertebral disc prolapse in a European brown
      bear (Ursus arctos arctos).
AB  - A 22-year-old male European brown bear (Ursus arctos arctos) was presented to the
      Onderstepoort Veterinary Academic Hospital after an acute onset of hind limb
      paralysis 4 days earlier. Previous radiographs revealed marked degenerative joint
      disease of the stifles, tarsi and digits. The clinical findings were consistent
      with acute disc prolapse. Lateral radiographs of the entire vertebral column were
      made as well as ventrodorsal pelvic radiographs. The latter were within normal
      limits. The vertebral column revealed multiple lesions consistent with chronic
      and acute disc herniations. Lateral compression of the caudal lumbar nerve roots
      could not be ruled out. Owing to multiple significant findings of the vertebral
      column and the poor prognosis for full recovery after surgery, the bear was
      euthanased. The diagnosis of an acute disc prolapse and multiple chronic disc
      herniations was confirmed on necropsy.

PMID- 16108535
TI  - Human malaria parasites in continuous culture. 1976.

PMID- 16108536
TI  - Reflections on the continuous cultivation of Plasmodium falciparum.

PMID- 16108537
TI  - In vivo and in vitro encystment of Echinochasmus liliputanus cercariae and
      biological activity of the metacercariae.
AB  - In vivo and in vitro encystment of the cercariae of Echinochasmus liliputanus and
      biological activity of the metacercariae were studied. In vivo encystment of
      cercariae occurred in the gills of goldfish, the second intermediate host.
      However, the cercariae also encysted in vitro in Locke solution (0.6x to 1.2x
      strength), 0.7-1.2% NaCI, artificial gastric juice, and human gastric juice.
      Locke or NaCI solutions were shown to be appropriate for in vitro encystment to
      occur within 24 hr; however, full-strength Locke solution was shown to be
      optimal. The 1-day-old metacercariae formed in vivo and treated in 0.1% sodium
      deoxycholate excystation medium at 37 C for 1 hr showed 88.5% excystation. The
      metacercariae formed in vitro, however, showed 88.6% and 85.0% excystation for
      normal and abnormal ones, respectively. Abnormal cysts at room temperature
      usually die within 10 days. About 70% of the normal cysts, both in vivo and in
      vitro, can still excyst after being stored in Locke 0.5x solution at 4 C for 3
      mo. Cysts formed in vivo and in vitro were equally infective. The encystment of
      the cercariae in vitro could be inhibited when the cercariae were treated with 1
      micromol silver nitrate. Because silver nitrate binds to the papillae, especially
      to the ciliated papillae, on the cercaria surface, it is suggested that papillary
      chemoreceptors may be involved in encystment of the cercariae. The finding of E.
      liliputanus cercariae encysting in vitro, especially in human gastric juice,
      might be helpful in elucidating mechanisms of the definitive hosts that are
      directly infected by the cercariae.

PMID- 16108538
TI  - Ultrastructure of spermiogenesis and the spermatozoon of Macracanthorhynchus
      hirudinaceus (Pallas, 1781) (Acanthocephala: Archiacanthocephala), a parasite of
      the wild boar Sus scrofa.
AB  - The present paper describes the ultrastructure of spermiogenesis and the
      spermatozoon of Macracanthorhynchus hirudinaceus, an acanthocephalan parasite of
      the wild boar Sus scrofa. At the beginning of spermatogenesis, spermatocytes
      exhibit synaptonemal complexes and 2 centrioles. In the spermatid, only 1
      centriole remains, generating a flagellum with a 9+2 pattern. Another
      ultrastructural feature observed during the spermiogenesis of M. hirudinaceus is
      the condensation of the chromatin, forming a "honeycomb" structure in the old
      spermatid and a homogeneous, electron-dense structure in the spermatozoon. The
      mature spermatozoon of M. hirudinaceus presents a reversed anatomy, as has been
      described previously in other species of the Acanthocephala. The spermatozoon is
      divided into 2 parts: an axoneme, and a nucleocytoplasmic derivative. The
      spermatozoon flagellum exhibits a 9+2 or 9+0 pattern. The process of
      spermiogenesis and the ultrastructural organization of the spermatozoon of M.
      hirudinaceus are compared with available data regarding other acanthocephalan
      species.

PMID- 16108539
TI  - Adaptation of Neospora caninum isolates to cell-culture changes: an argument in
      favor of its clonal population structure.
AB  - Neospora caninum, a recently recognized protozoan parasite of animals, is
      considered to be a major cause of bovine abortion worldwide. Although its life
      cycle is not completely known, recent studies suggest that the sexual stage
      occurs in dogs. The prevalence of sexual reproduction in N. caninum, however, is
      unknown. We investigated the ability of 3 N. caninum isolates (NC-1, NC-SweB1,
      and NC-Liverpool) to propagate asexually for approximately 250 parasite
      generations in a cell line in which they had not been cultured previously. The
      malthusian parameter of fitness was estimated for each isolate from 10
      independent replicates of tachyzoites at the beginning as well as at the end of
      the experimental period. Derived and ancestral values for mean fitness were
      compared both within and among NC-1, NC-SweB1, and NC-Liverpool isolates. Results
      showed a significant increase in mean fitness for the 3 N. caninum isolates at
      the end of the experimental period. These findings indicate that N. caninum can
      adapt to new environmental conditions without the help of sexual recombination,
      supporting the idea that this parasite has, at least potentially, the capacity
      for maintaining clonal propagation in nature.

PMID- 16108540
TI  - Combining phylogenetic and ecological information into a new index of host
      specificity.
AB  - Host specificity has 2 independent facets: the extent to which different host
      species are used by a parasite, and the phylogenetic distances among these hosts.
      Although the number of host species exploited by a parasite commonly is used as a
      measure of host specificity, it fails to capture ecological and phylogenetic
      differences among hosts. Here, a new index of host specificity, S(TD)*, is
      developed and illustrated. This index measures the average taxonomic distinctness
      among the host species used by a parasite, weighted for the parasite's prevalence
      in the different hosts. For a given number of host species, the index approaches
      its minimum value when a parasite achieves high prevalence in a few closely
      related host species, and the index approaches its highest value when a parasite
      reaches its highest prevalence values in distantly related host species. Simple
      hypothetical examples are used to demonstrate the index's computation and some of
      its properties. The new index is influenced independently both by the taxonomic
      (or phylogenetic) affinities of a set of host species and by the distribution of
      prevalence values among these hosts. A single value cannot truly capture all the
      nuances of a phenomenon as complex as host specificity; nevertheless, the
      proposed index incorporates the features of specificity that are most relevant to
      parasitologists and will be a useful tool for comparative studies.

PMID- 16108541
TI  - An efficient strategy to estimate intensity and prevalence: sampling
      metacercariae in fishes.
AB  - Accurate estimates of population-level parameters of parasites, such as
      prevalence and mean intensity, require large sample sizes. The processing of such
      samples becomes an overwhelming task when parasites are abundant, as with
      trematode metacercariae in fishes. In the present study, a subsampling method
      reduced processing time while maintaining an accurate estimation of metacercariae
      prevalence and intensity across 3 trematode species and 2 fish species. By double
      sampling, we generated regression models to predict total intensity from a
      combination of subsamples. The key to this approach lies in choosing the best
      strategy from a large number of potential subsampling routines. We selected the
      most efficient routine by weighing the costs and benefits of each. This approach,
      however, could not provide an estimate of parasite abundance when no parasites
      occurred in the initial subsample. To estimate prevalence accurately, our
      subsampling algorithm prescribed an additional sampling sequence using a new,
      optimal regression model. In addition, we optimized the technique to measure
      three parasite species infecting a single host simultaneously. This efficient
      subsampling procedure decreased the overall processing time per host by up to 91%
      while obtaining accurate (R2 > 0.8) estimates for both prevalence and intensity.

PMID- 16108542
TI  - Empruthotrema stenophallus n. sp. (Monogenea: Monocotylidae) from the nasal
      tissue of Dasyatis kuhlii (Dasyatidae) from Sabah, Borneo, Malaysia.
AB  - Empruthotrema stenophallus n. sp. (Monogenea: Monocotylidae) is described from
      specimens from the nasal tissue of the blue-spotted maskray Dasyatis kuhlii
      (Muller and Henle, 1841) collected in shallow waters off Pulau Banggi and Pulau
      Mabul, Sabah, Borneo, Malaysia. This is the first monogenean species to be
      described from an elasmobranch collected from Sabah. E. stenophallus can be
      distinguished from the other 6 members of the genus by the morphology of the
      sclerotized male copulatory organ, which is narrow, short, and distally tapered.
      E. dasyatidis Whittington and Kearn, 1992, previously documented from the nasal
      tissue of several of elasmobranch species from Australia, is recorded from 8 host
      species distributed around Malaysian Borneo. These represent new host and
      locality records for this monocotylid. The difficulties in identifying species of
      Empruthotrema and the apparent lack of host specificity by some members of the
      genus are discussed.

PMID- 16108543
TI  - Amblyomma latepunctatum, a valid tick species (Acari: Ixodidae) long
      misidentified with both amblyomma incisum and Amblyomma scalpturatum.
AB  - In 2000, we initiated an investigation on the tick fauna of Rondonia State, where
      we collected many specimens of Amblyomma scalpturatum Neumann, 1906 and Amblyomma
      incisum Neumann, 1906. In addition, we also collected a third group of ticks that
      were morphologically closely related to those 2 species, but sufficiently
      different to be considered a distinct species; members of this group were
      subsequently identified as Amblyomma latepunctatum Tonelli-Rondelli, 1939,
      through comparison with the type specimens of this taxon. Herein, we redescribe
      both sexes of A. scalpturatum and A. incisum, the female of A. latepunctatum, and
      provide the first description of the male of this latter species. Molecular
      analysis of the second internal transcribed spacer (ITS2) from rDNA of specimens
      of the 3 species supports morphological results. Examination of both A.
      scalpturatum and A. incisum deposited in different tick collections revealed that
      A. latepunctatum appeared relatively frequently in the vials believed to contain
      specimens of A. incisum or A. scalpturatum. Before this study, A. latepunctatum
      was considered a synonym of A. scalpturatum. Herein, we provide morphological and
      molecular evidence to validate the species A. latepunctatum. The South American
      tapir (Tapirus terrestris) seems to be the primary host for the adult stage of A.
      latepunctatum, A. scalpturatum, and A. incisum.

PMID- 16108544
TI  - Serotonin-induced muscular activity in Schistosoma mansoni larval stages:
      importance of 5-HT transport and role in daughter sporocyst production.
AB  - Mother sporocysts of Schistosoma mansoni transport exogenously supplied serotonin
      (5-hydroxytrypamine; 5-HT), and respond to it with increases in motility. In the
      present study, we investigated the importance of 5-HT transporter activity in the
      manifestation of these 5-HT-induced motility changes, and further examined the
      role of 5-HT in the development of daughter sporocysts in vitro. Serotonin
      induced motility of in vitro-derived sporocysts is not inhibited by
      antidepressant compounds, e.g., fluoxetine, that block 5-HT transport, suggesting
      that the receptors responsible for motility responses to 5-HT are surface
      exposed. Using a sporocyst in vitro culture system, we show that depletion of
      larval stores of 5-HT reduces production of daughter sporocysts, the second
      intramolluscan larval stage. Moreover, we demonstrate a strong correlation
      between endogenous 5-HT levels and basal mother sporocyst muscle activity.
      Overall, these data suggest that larval stages of S. mansoni can detect exogenous
      5-HT via surface-exposed receptors, and they are consistent with the hypothesis
      that endogenous stores of 5-HT are important for the proper regulation of
      muscular contractions in mother sporocysts, and for the successful emergence of
      daughter sporocysts.

PMID- 16108545
TI  - Axenic promastigote forms of Leishmania (Viannia) lainsoni as an alternative
      source for Leishmania antigen production.
AB  - The present study demonstrates that axenic cultures of Leishmania (Viannia)
      lainsoni produce larger cell masses in NNN-LIT medium, as well as higher amounts
      of total proteins in cell extracts, than Leishmania (Leishmania) amazonensis.
      Antigenicity of L. (V.) lainsoni whole promastigotes is similar to that of L.
      (L.) amazonensis, as demonstrated by an indirect immunofluorescence diagnostic
      test using sera from human patients and dogs infected with visceral
      leishmaniasis. Infectivity of the L. (V.) lainsoni strain used in the present
      work was demonstrated by the detection by transmission-electron microscopy of
      tissue amastigotes in skin lesion samples from an experimentally infected
      hamster. Incubation of lesion fragments in NNN-LIT medium allowed us to obtain
      promastigote forms, which could be cultivated successfully in vitro. lsoenzyme
      analysis of such promastigotes confirmed the parasite strain as L. (V.) lainsoni,
      as compared to other Leishmania reference strains. Our data indicate that L. (V.)
      lainsoni is a useful alternative source for antigen production as well for use in
      assays that depend on large cell volumes of Leishmania spp. parasites.

PMID- 16108546
TI  - Isolation, tissue distribution, and molecular characterization of Toxoplasma
      gondii from chickens in Grenada, West Indies.
AB  - The prevalence of Toxoplasma gondii in free-range chickens is a good indicator of
      the prevalence of T. gondii oocysts in the soil because chickens feed from the
      ground. The prevalence of T. gondii in 102 free-range chickens (Gallus
      domesticus) from Grenada was determined. Antibodies to T. gondii were assayed by
      the modified agglutination test (MAT). Antibodies were found in 53 (52%) chickens
      with titers of 1:5 in 6, 1:10 in 4, 1:20 in 4, 1:40 in 4, 1:80 in 15, 1:160 in 9,
      1: 320 in 5, 1:640 in 4, and 1:1,280 or greater in 2. Hearts, pectoral muscles,
      and brains of 43 seropositive chickens with MAT titers of 1:20 or greater were
      bioassayed individually in mice. Tissues of each of 10 chickens with titers of
      1:5 and 1:10 were pooled and bioassayed in mice. Tissues from the remaining 49
      seronegative chickens were pooled and fed to 4 T. gondii-free cats. Feces of cats
      were examined for oocysts; they did not shed oocysts. T. gondii was isolated from
      35 of 43 chickens with MAT titers of 1:20 or greater; from the hearts, brains,
      and pectoral muscles of 2, hearts and brains of 20, from the hearts alone of 11,
      and brains alone of 2. T. gondii was isolated from 1 of 10 chickens with titers
      of 1:5 or 1:10. All 36 T. gondii isolates were avirulent for mice. Genotyping of
      these 36 isolates using polymorphisms at the SAG2 locus indicated that 29 were
      Type III, 5 were Type I, 1 was Type II, and 1 had both Type I and Type III.
      Genetically, the isolates from Grenada were different from those from the United
      States; Type II was the predominant type from the United States. Phenotypically,
      all isolates from Grenada were avirulent for mice, whereas those from Brazil were
      mouse-virulent. This is the first report of isolation of T. gondii from chickens
      from Grenada, West Indies.

PMID- 16108547
TI  - Performance of a Western immunoblot assay to detect specific anti-Toxoplasma
      gondii IgG antibodies in human saliva.
AB  - Toxoplasma gondii represents the most prominent infectious parasitic organism
      found in humans. While normally asymptomatic in healthy individuals,
      toxoplasmosis can cause abortion in patients during pregnancy, or can be fatal in
      immunosupressed individuals such as persons suffering from acquired
      immunodeficiency syndrom (AIDS). Toxoplasma gondii infection in humans is
      routinely assesssed by serological means. Here, we show that detection of anti-T.
      gondii IgG is also possible using a non-invasive methodology employing saliva.
      Sera and saliva of 201 healthy volunteers were investigated for the presence of
      anti-T. gondii-IgG antibodies by immunoblotting. The sera of 59 (29.4%)
      individuals showed IgG antibodies against T. gondii by ELISA, Vidas, and
      immunoblotting; 58 (98.3%) of these were also positive for anti-T. gondii IgG in
      the saliva immunoblot, with diagnostic relevant bands of Mr of 32-35 kDa and 40
      45 kDa. The saliva immunoblot test exhibits a specificity of 100% and a
      sensitivity of 98.5%. Thus, saliva could be used as an alternative, non-invasive
      means for the detection of specific anti-T. gondii IgG in humans.

PMID- 16108548
TI  - Neospora caninum antigens defined by antigen-dependent bovine CD4+ T cells.
AB  - Neosporosis is an important cause of pregnancy loss in cattle worldwide. The
      objective of the present study was to identify Neospora caninum antigens as
      vaccine candidates using antigen-specific, short-term CD4+ T cells established
      from N. caninum-immunized and -challenged cows. Whole N. caninum tachyzoite
      lysate was separated into 6 fractions by DEAE anion-exchange chromatography using
      high-pressure liquid chromatography (HPLC). The CD4+ T-cell proliferation assay
      results indicated that antigenic activity was associated with proteins from HPLC
      fractions 4-6, with fraction 5 exhibiting the highest antigenic activity. Also,
      SDS-PAGE analysis revealed a 16-kDa protein in fractions 4-6 that was recognized
      by anti-N. caninum antibodies. This 16-kDa protein was absent in other fractions,
      and it may be a target of a T-cell response in cattle. Further identification of
      immunogenic proteins of N. caninum may facilitate development of subunit vaccines
      against neosporosis.

PMID- 16108549
TI  - Gastrointestinal parasites of the colobus monkeys of Uganda.
AB  - From August 1997 to July 2003, we collected 2,103 fecal samples from free-ranging
      individuals of the 3 colobus monkey species of Uganda-the endangered red colobus
      (Piliocolobus tephrosceles), the eastern black-and-white colobus (Colobus
      guereza), and the Angolan black-and-white colobus (C. angolensis)--to identify
      and determine the prevalence of gastrointestinal parasites. Helminth eggs,
      larvae, and protozoan cysts were isolated by sodium nitrate flotation and fecal
      sedimentation. Coprocultures facilitated identification of helminths. Seven
      nematodes (Strongyloides fulleborni, S. stercoralis, Oesophagostomum sp., an
      unidentified strongyle, Trichuris sp., Ascaris sp., and Colobenterobius sp.), 1
      cestode (Bertiella sp.), 1 trematode (Dicrocoeliidae), and 3 protozoans
      (Entamoeba coli, E. histolytica, and Giardia lamblia) were detected. Seasonal
      patterns of infection were not apparent for any parasite species infecting
      colobus monkeys. Prevalence of S. fulleborni was higher in adult male compared to
      adult female red colobus, but prevalence did not differ for any other shared
      parasite species between age and sex classes.

PMID- 16108550
TI  - Geographic distribution of the muscle-dwelling nematode Parelaphostrongylus
      odocoilei in North America, using molecular identification of first-stage larvae.
AB  - Molecular identification of dorsal-spined larvae (DSL) from fecal samples
      indicates that the protostrongylid parasite Parelaphostrongylus odocoilei
      occupies a broader geographic range in western North America than has been
      previously reported. We analyzed 2,124 fecal samples at 29 locations from
      thinhorn sheep (Ovis dalli dalli and O. d. stonei), bighorn sheep (Ovis
      canadensis canadensis and O. c. californiana), mountain goats (Oreamnos
      americanus), woodland caribou (Rangifer tarandus caribou), mule deer (Odocoileus
      hemionus hemionus), and black-tailed deer (O. h. columbianus). The DSL were
      recovered from populations of thinhorn sheep south, but not north, of the Arctic
      Circle, and they were not recovered from any of the bighorn sheep populations
      that we examined. In total, DSL were recovered from 20 locations in the United
      States and Canada (Alaska, Yukon Territory, Northwest Territories, British
      Columbia, Alberta, and California). The DSL were identified as P. odocoilei by
      comparing sequences of the second internal transcribed spacer (ITS2) region of
      ribosomal RNA among 9 protostrongylid species validated by adult comparative
      morphology. The ITS2 sequences were markedly different between
      Parelaphostrongylus and other protostrongylid genera. Smaller fixed differences
      served as diagnostic markers for the 3 species of Parelaphostrongylus. The ITS2
      sequences (n = 60) of P. odocoilei were strongly conserved across its broad
      geographic range from California to Alaska. Polymorphism at 5 nucleotide
      positions was consistent with multiple copies of the ITS2 within individual
      specimens of P. odocoilei. This work combines extensive fecal surveys,
      comparative morphology, and molecular diagnostic techniques to describe
      comprehensively the host associations and geographic distribution of a parasitic
      helminth.

PMID- 16108551
TI  - Cloning and nucleotide sequence of a full-length cDNA encoding Ascaris suum
      phosphofructokinase.
AB  - The nucleotide sequence of a full-length cDNA encoding phosphofructokinase (PFK)
      enzyme from the parasitic nematode Ascaris suum was determined. The entire
      sequence of 2,653 bases comprises a single open reading frame of 2,452 bases and
      a noncoding region of 201 bases after the stop codon. The mature protein contains
      812 amino acids and has a molecular mass of 90,900 Da. The amino acid sequences
      of several peptides derived from the purified protein show excellent
      correspondence with the translated nucleotide sequence. Comparison of the amino
      acid sequence of the protein with those of 3 other worms as well as those of
      human, rabbit, and bacterial enzymes reveals highly conserved regions interrupted
      with stretches of lesser sequence similarity. Analyses of the subunit primary
      structure reveal, as in other eukaryotic PFKs, that the amino-terminal half is
      homologous to the carboxy-terminal half, supporting the hypothesis that the PFK
      gene evolved by duplication of the prokaryotic gene and that the allosteric sites
      arose by mutations at the catalytic site. The location of the phosphorylation
      site is unique and different compared with other PFKs and plays a key role in
      regulation of the enzyme activity. Structural motifs such as the putative
      substrate and effector binding domains and also the key amino acids involved
      therein are clearly identified by alignment of all the PFK protein sequences.

PMID- 16108552
TI  - Two new species of Pharyngodonidae (Nematoda: Oxyuroidea) and other nematodes in
      Agama caudospina (Squamata: Agamidae) from Kenya, Africa.
AB  - Parapharyngodon kenyaensis n. sp. and Thelandros samburuensis n. sp. (Nematoda:
      Pharyngodonidae) from the large intestine of the agamid lizard (Agama caudospina)
      are described and illustrated. Parapharyngodon kenyaensis n. sp. is the 41st
      species assigned to the genus, and it differs from other species in that genus by
      possessing 3 pairs of caudal papillae, cloacal lip adornment, and spicules of 112
      120 microm in length. Thelandros samburuensis n. sp. is the 31st species assigned
      to the genus, and it differs from other species in that genus by possessing
      swollen posterior annulations, 6 caudal papillae, a smooth anterior cloacal lip,
      and spicules of 43-52 microm in length. In addition to the 2 new nematode
      species, Abbreviata ortleppi (Nematoda: Physalopteridae) and Strongyluris ornata
      (Nematoda: Heterakidae) were found.

PMID- 16108553
TI  - New species of Oswaldocruzia (Nematoda: Molineoidae), new species of Rhabdias
      (Nematoda: Rhabdiasidae), and other helminths in Rana cf. forreri (Anura:
      Ranidae) from Costa Rica.
AB  - Oswaldocruzia costaricensis n. sp. (Strongylida: Molineidae) from the intestines
      and Rhabdias savagei n. sp. (Rhabditida: Rhabdiasidae) from the lungs of Rana cf.
      forreri (Anura: Ranidae) are described and illustrated. Oswaldocruzia
      costaricensis represents the 77th species assigned to the genus and differs from
      the other Neotropical species in the genus by possessing a Type II bursa and long
      cervical alae. Rhabdias savagei represents the 47th species assigned to the genus
      and differs from other Neotropical species in the genus by possession of 4 lips
      and a postequatorial vulva. Rana cf. forreri was also found to harbor the
      trematodes, Haematoloechus parcivitellarius and Megalodiscus temperatus, the
      nematodes, Aplectana incerta, Aplectana itzocanensis, Cosmocerca podicipinus,
      Foleyellides striatus, Subulascaris falcaustriformis, and a larva of the nematode
      Brevimulticaecum sp. Cosmocerca panamaensis is considered to be a synonym of
      Cosmocerca podicipinus.

PMID- 16108554
TI  - Further description of Procamallanus (Spirocamallanus) halitrophus comb. n.
      (Nematoda: Camallanidae) from flounder off the Brazilian coast by light and
      scanning electron microscopy.
AB  - Procamallanus (Spirocamallanus) halitrophus Fusco and Overstreet, 1978 from the
      intestines of flounders (Syacium papillosum and Citharichthys macrops) from the
      coast of the State of Rio de Janeiro, Brazil, is redescribed. This study, which
      is based on results obtained by light and scanning electron microscopy, clarifies
      many morphological aspects of this species. Some taxonomic features, such as the
      cephalic structures, the topography of the cuticle, the vulva, the localization
      of caudal papillae on males, and the excretory pore, are observed for the first
      time. C. macrops represents a new host record, and Rio de Janeiro is a new
      geographical record for this species.

PMID- 16108555
TI  - First report of parasites from pinnipeds in the Galapagos Islands, Ecuador, with
      a description of a new species of Philophthalmus (Digenea: Philophthalmidae).
AB  - A new species of digenetic trematode and 2 species of ectoparasites from Zalophus
      wollebaeki Silvertsen, 1953 (Carnivora: Otariidae) in the Galapagos Islands,
      Ecuador, are reported. These include an eye fluke of Philophthalmus Looss, 1899
      (Echinostomata: Philophthalmidae) as well as, to our knowledge, the first report
      of Antarctophthirus microchir (Trouessart and Neumann, 1888) Enderlein, 1906
      (Arthropoda: Anoplura) and Orthohalarachne diminuata (Doetschman, 1944) Newell,
      1947 (Arthropoda: Acarina) from this host and location. Philophthalmus zalophi n.
      sp. differs from the 4 other marine species of Philophthalmus (P. andersoni
      Dronen and Penner, 1975; P. burrili Howell and Bearup, 1967; P. hegeneri Penner
      and Fried, 1963; and P. larsoni Penner and Trimble, 1970) by its mammalian host,
      large body size, lack of tegumental spines, posterior length of seminal vesicle,
      placement of genital pore, size ratio of oral sucker to acetabulum, shape and
      size of testes, and size ratio of ovary to testis.

PMID- 16108556
TI  - A pathogenic new species of Eimeria from the pygmy rabbit, Brachylagus
      idahoensis, in Washington and Oregon, with description of the sporulated oocyst
      and intestinal endogenous stages.
AB  - In January 2003, fecal samples from 13 live pygmy rabbits, Brachylagus idahoensis
      (Merriam, 1891), were collected at the Oregon Zoo in Portland, Oregon, and sent
      to the University of New Mexico (UNM), Albuquerque, New Mexico, to be examined
      for coccidia. In July 2004, 14 more fecal samples were collected and sent to UNM,
      6 from some of the same rabbits and 8 from 16 other rabbits (4 were pooled
      samples from siblings). In addition, tissue sections from 3 dead rabbits (2 from
      the Oregon Zoo, 1 from Washington State University) also were examined. Two of 4
      (50%) pooled fecal samples and 8 of 17 (47%) 1-rabbit samples were positive for a
      single species of Eimeria, which we describe here as a new species. Sporulated
      oocysts were subspheroidal, 25.6 x 23.8 (22-28 x 21-27) microm, with a
      length:width (L:W) ratio of 1.1 (1.0-1.2). A micropyle (approximately 2 microm
      wide) and 0-1 polar granules were present, but an oocyst residuum was absent.
      Sporocysts were ellipsoidal, 13.4 x 8.1 (11-16.5 x 7.5-9) microm, with a L:W
      ratio of 1.7 (1.3-2.2), and they had a Stieda body and sporocyst residuum. Tissue
      sections showed a heavy infection of the villous epithelial cells of the proximal
      and mid-small intestine with coccidial endogenous stages, but no stages were
      found in liver hepatocytes. Meronts with approximately 46 (26-70) merozoites per
      infected cell appeared to be fully developed and were subspheroidal, 14.8 x 13.9
      (13-18 x 10.5-16.5) microm. Developing macro- and microgamonts were
      indistinguishable from each other and were spheroidal to subspheroidal, 10.4 x
      9.5 (9-11 x 7.5-10.5) microm. Mature macrogamonts were spheroidal to
      subspheroidal, 14.2 x 13.7 (12-17 x 11-16) microm, and mature microgamonts were
      smaller and subspheroidal, 11.9 x 10.8 (10.5-13 x 9-12) microm. This eimerian
      seems to be extremely pathogenic to young pygmy rabbits, and given the precarious
      nature of this unique genetic population, it appears to be an emerging pathogen
      that deserves immediate further study.

PMID- 16108557
TI  - Cryptosporidium bovis n. sp. (Apicomplexa: Cryptosporidiidae) in cattle (Bos
      taurus).
AB  - A new species of Cryptosporidium, C. bovis, is described. Oocysts of C. bovis,
      previously identified as Cryptosporidium genotype Bovine B (GenBank AY120911),
      are morphologically indistinguishable from those of C. parvum. They are excreted
      fully sporulated and contain 4 sporozoites, but lack sporocysts. Oocysts measure
      4.76-5.35 microm (mean = 4.89 microm) x 4.17-4.76 microm (mean = 4.63 microm),
      with a length-to-width ratio of 1.06 (n = 50). Oocysts were not infectious for
      neonatal BALB/ c mice, but were infectious for 2 calves that were previously
      infected with C. parvum. Oocysts were not infectious for 2 experimentally exposed
      lambs less than 1 wk of age and were not detected in 42 lambs 2-3 mo of age, but
      were detected in a 2-wk-old lamb. In an earlier study, 79 of 840 calves on 14
      dairy farms in 7 states were found infected with the new species. Most calves
      were 2-7 mo of age and none exhibited signs of diarrhea. This new species has
      been found in 10 of 162 calves aged 9 to 11 mo on a beef farm in Maryland.
      Fragments of the 18S rDNA, HSP-70, and actin genes were amplified by PCR, and
      purified PCR products were sequenced. Multilocus analysis of the 3 unlinked loci
      demonstrated the new species to be distinct from C. parvum and also demonstrated
      a lack of recombination, providing further evidence of species status. Based on
      these biological and molecular data, we consider this highly prevalent
      Cryptosporidium that infects primarily postweaned calves to be a new species and
      propose the name Cryptosporidium bovis n. sp. for this parasite.

PMID- 16108558
TI  - Chaulioleptos haywardi n. gen., n. sp. (Digenea: Sanguinicolidae) from Filimanus
      heptadactyla (Perciformes: Polynemidae) of Moreton Bay, Australia.
AB  - Here we describe the first species of sanguinicolid blood fluke (Trematoda:
      Digenea) from a polynemid fish. Chaulioleptos haywardi n. gen., n. sp. is
      described from Filimanus heptadactyla Cuvier, 1829 (Perciformes: Polynemidae),
      the sevenfinger threadfin from Sandgate, Moreton Bay (southeast Queensland,
      Australia). Chaulioleptos haywardi differs from existing sanguinicolid genera in
      the combined possession of the following 7 characters: 2 testes, an entirely
      postovarian uterus, a uterine chamber, separate genital pores, an H-shaped
      intestine with abbreviated anterior caeca, tegumental spines in incomplete ventro
      marginal transverse rows that are continuous along the length of the body, and
      vitelline follicles that are tightly compacted and subsequently appear to form a
      solid branching mass occupying the area anterior to intestinal bifurcation and
      extending posteriorly to the level of the posterior margin of the anterior
      testis. Chaulioleptos haywardi is most closely related to Paracardicola Martin,
      1960 and Adelomyllos Nolan and Cribb, 2004.

PMID- 16108559
TI  - Molecular characterization of isosporoid coccidia (Isospora and Atoxoplasma spp.)
      in passerine birds.
AB  - Prevalence and disease caused by isosporoid coccidia in passerine birds are well
      recognized, but confusion about the life cycles of the parasites has led to
      taxonomic inconsistencies. In this study, we characterized segments of the
      chromosomal small and large-subunit ribosomal RNA (rRNA) genes of coccidial
      parasites from 23 species of passerine birds, as well as heat shock protein 70,
      apicoplast rRNA, and chromosomal 5.8s rRNA genes from a subgroup of these
      animals, and we correlated genetic data with morphologic findings for different
      parasite developmental stages, host phylogeny, and overall taxonomic relations
      within the phylum Apicomplexa. Our findings indicate that isosporoid coccidia of
      passerine birds are monophyletic but exhibit substantial diversity, with most
      avian species having one or several unique parasite lineages that underwent
      synchronous speciation with their hosts, interrupted by sporadic episodes of
      lateral transmission across species and families. Molecular analyses support a
      homoxenous life cycle, with sexual forms occurring chiefly in the intestines and
      asexual merozoites present systemically. Rarely, extraintestinal sexual stages
      can occur. The passerine coccidia are genetically most closely related to species
      of Eimeria rather than Isospora. We suggest that these parasites, whether
      identified from blood merozoite stages or fecal oocysts, be provisionally grouped
      as a homogeneous clade of individual species in a single taxon and formally named
      when reliable criteria allowing reclassification of related genera in the
      suborder Eimeriina are clarified.

PMID- 16108560
TI  - Urotrema shirleyae n. sp. (Trematoda: Digenea: Urotrematidae) in Norops oxylophus
      and N. cupreus (Squamata: Iguania: Polychrotidae) from the Area de Conservacion
      Guanacaste, Costa Rica.
AB  - A new species of Urotrema inhabits Norops oxylophus and Norops cupreus from the
      Area de Conservacion Guanacaste, Costa Rica. The new species is most similar to
      Urotrema scabridum but differs by having a relatively longer esophagus, at least
      10% of the total body length versus 4-8% in U. scabridum; an oral sucker width:
      ventral sucker width ratio less than 1 : 1 (averaging 1 : 0.76) versus 1 : 1 or
      greater; an oral sucker width : pharyngeal width ratio less than 1 : 0.5
      (averaging 1 : 0.42) versus greater than 1 :0.5; and by having many transversely
      oriented posttesticular uterine loops versus a few vertically oriented
      posttesticular uterine loops.

PMID- 16108561
TI  - Trypanosoma saimirii Rodhain, a junior synonym of Trypanosoma rangeli Tejera.
AB  - In the present study, we used sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis to compare polypeptides of trypanosomes isolated by hemoculture
      of squirrel monkeys displaying Trypanosoma saimirii blood trypomastigotes, with
      other trypanosomes that infect primates to evaluate the validity of T. saimirii.
      The polypeptide profiles of trypanosomes isolated directly from squirrel monkeys
      or after their passage in mice were identical to those of 3 standard strains of
      T. rangeli, but they were distinct from those of T. cruzi, T. conorhini, and T.
      minasense. These results strengthen previous morphological and biological
      findings by Rodhain on trypanosomes of the squirrel monkey and lead to the
      conclusion that T. saimirii is indeed a junior synonym of T. rangeli.

PMID- 16108562
TI  - Reduced infection and protection from clinical signs of cerebral neosporosis in
      C57BL/6 mice vaccinated with recombinant microneme antigen NcMIC1.
AB  - NcMIC1 is a 460 amino acid Neospora caninum microneme protein implicated in host
      cell adhesion and invasion processes. In this study, we assessed the potential
      protectivity of NcMIC1-based vaccination against experimental N. caninum
      infection in mice, employing both recombinant antigen vaccines and DNA vaccines.
      Recombinant NcMIC1 (recNcMIC1) was expressed in Escherichia coli as gluthatione-S
      transferase-fusion protein. The corresponding NcMIC1 cDNA was cloned into the
      pcDNA3.1 expression plasmid (pcDNA-MIC1), and expression was checked in
      transfected Vero cells. Mice (10 animals/group) were vaccinated either with
      recNcMIC1 antigen suspended in Ribi-adjuvant (3 intraperitoneal injections),
      pcDNA-NcMIC1 (3 intramuscular injections), or pcDNA-NcMIC1 (twice
      intramuscularly), followed by 1 intraperitoneal recNcMIC1 antigen boost. Control
      groups included corresponding treatments with adjuvant, pcDNA3.1 without insert,
      and PBS (= infection control). All vaccinated and control groups were then
      challenged intraperitoneally with 2 x 10(6) N. caninum tachyzoites. Animals were
      inspected daily for a period of 3 wk postinfection (PI). At day 21, all animals
      were killed and assessed for infection. Before day 21 PI, clinical signs such as
      walking disorders, rounded back, apathy, and paralysis occurred in infection
      controls (50% of the mice), pcDNA and adjuvant controls (20% each), and the
      combined pcDNA-NcMIC1/recNcMIC1-treated group (30%). No clinical symptoms were
      observed in the recNcMIC1 and pcDNA-NcMIC1 vaccinated groups. All mice were
      positive for cerebral N. caninum infection as assessed by PCR of brain tissue.
      However, quantitative real-time PCR revealed that the infection intensity was
      significantly reduced in the group vaccinated with recNcMIC1 antigen.
      Immunohistochemistry confirmed these findings. In contrast, the infection
      intensity was highest in the group vaccinated with the pcDNA-NcMIC1/recNcMIC1
      combination, indicating that the sequential application of the DNA vaccine and
      recombinant antigen had a deleterious effect. Serological analysis showed that
      only recNcMIC1-immunized animals generated detectable antibody levels recognizing
      native NcMIC1. Thus, of all protocols applied here, only recNcMIC1 vaccination
      appears to be suited to reduce cerebral infection in mice challenged with N.
      caninum tachyzoites.

PMID- 16108563
TI  - Embryo vaccination against Eimeria tenella and E. acervulina infections using
      recombinant proteins and cytokine adjuvants.
AB  - Avian coccidiosis is an intestinal disease caused by protozoa of the genus
      Eimeria. To investigate the potential of recombinant protein vaccines to control
      coccidiosis, we cloned 2 Eimeria sp. genes (EtMIC2 and 3-1E), expressed and
      purified their encoded proteins, and determined the efficacy of in ovo
      immunization to protect against Eimeria infections. Immunogen-specific serum
      antibody titers, parasite fecal shedding, and body weight gains were measured as
      parameters of disease. When administered alone, the recombinant EtMIC2 gene
      product induced significantly higher antibody responses, lower oocyst fecal
      shedding, and increased weight gains compared with nonvaccinated controls
      following infection with E. tenella. Combined embryo immunization with the EtMIC2
      protein plus chicken cytokine or chemokine genes demonstrated that all 3
      parameters of vaccination were improved compared with those of EtMIC2 alone. In
      particular, covaccination with EtMIC2 plus interleukin (IL)-8, IL-16,
      transforming growth factor-beta4, or lymphotactin significantly decreased oocyst
      shedding and improved weight gains beyond those achieved by EtMIC2 alone.
      Finally, individual vaccination with either EtMIC2 or 3-1E stimulated protection
      against infection by the heterologous parasite E. acervulina. Taken together,
      these results indicate that in ovo vaccination with the EtMIC2 protein plus
      cytokine/chemokine genes may be an effective method to control coccidiosis.

PMID- 16108564
TI  - Oral administration of hyperimmune anti-Cryptosporidium parvum ovine colostral
      whey confers a high level of protection against cryptosporidiosis in newborn NMRI
      mice.
AB  - Hyperimmune anti-Cryptosporidium parvum ovine colostral whey (HOCW) was tested to
      determine whether it conferred passive immunity to newborn NMRI mice. Three HOCWs
      (groups IV-VI), 2 nonimmune colostral wheys (groups II and III), and PBS (group
      I) were administered once (experiment A) and 3 times (experiment B) daily from -1
      to 15 days postinfection (PI). Mice in groups I-VI were inoculated with 5 x 10(5)
      oocysts (day 0 PI), and group VII mice acted as controls. The percentage and
      intensity of infection were measured at 6, 9, 12, and 16 days PI. In experiment
      A, HOCW did not reduce significantly the percentage and intensity of infection
      except for mice in group VI treated with HOCW with the highest titers of anti-C.
      parvum antibodies. In contrast, no infection was detected in between 18.7 and
      62.5% of the mice in groups IV-VI in experiment B. Furthermore, in these groups,
      the intensity of the infection decreased significantly, ranging from 83.5 to
      97.4%. Thus, HOCW did not completely avoid infection, but a high level of
      protection was observed, being proportional to the titer of specific antibodies
      and the amount of whey administered orally. Finally, group VII showed no presence
      of oocysts.

PMID- 16108565
TI  - Effects of repeated anthelmintic treatment on Enterobius vermicularis infection
      in chimpanzees.
AB  - Effects of repeated treatment with pyrantel pamoate on Enterobius vermicularis
      infection in chimpanzees were assessed by observing worms discharged in the feces
      after administration of anthelmintic treatment. Three of 9 chimpanzees reared in
      a zoological garden in Japan were subjected to fecal worm count and morphometric
      observation, and all were given oral pyrantel pamoate 6 times at 10-day intervals
      simultaneously. Following the first and second treatments, more than 30,000
      pinworms were discharged from 1 chimpanzee. The number of discharged worms
      abruptly decreased after the third treatment, and only a few worms were recovered
      after the fifth treatment, indicating that repeated treatment at short intervals
      was very effective. Complete eradication was not achieved, however, presumably
      because of reinfection. The female proportion among discharged worms tended to
      increase as the treatment was repeated.

PMID- 16108566
TI  - A restriction enzyme-based assay to distinguish between avian hemosporidians.
AB  - We describe a reliable and relatively inexpensive method for detecting and
      differentiating between the commonly studied avian blood parasite genera
      Haemoproteus, Plasmodium, and Leucocytozoon. The assay takes advantage of a
      Haemoproteus-specific restriction site identified by sequencing full
      mitochondrial genomes from two Haemoproteus and three Plasmodium lineages and an
      adjacent, genus-specific restriction site identified in Leucocytozoon spp. The
      assay was sensitive to simulated parasitemias of approximately 8 x 10(-6) per
      erythrocyte and was 100% accurate in differentiating between parasite genera
      isolated from a broad geographical and taxonomic sampling of infected hosts.

PMID- 16108567
TI  - Glucocorticosteroid hormone treatment of larval treefrogs increases infection by
      Alaria sp. trematode cercariae.
AB  - In many amphibian species, an apparent increase has occurred in the prevalence of
      limb deformities caused by parasitic trematodes. We are interested in the role of
      environmental stressors in increasing these infections in amphibians. One
      mechanism by which environmental stressors could act to increase disease
      prevalence is to increase circulating levels of glucocorticosteroid hormones,
      which are released in response to stressors and can be immunosuppressive. In the
      present study, we treated gray treefroZg tadpoles (Hyla versicolor) with
      exogenous corticosterone, which is the main glucocorticosteroid "stress" hormone
      in amphibians. We then exposed treated tadpoles to Alaria sp. cercariae and
      scored the number of mesocercariae that successfully infected the tadpoles. In
      addition, we assayed one function of the immune response by counting the number
      of circulating eosinophilic granulocytes, which are thought to be important in
      immune responses to macroparasites. Tadpoles treated with exogenous
      corticosterone developed higher parasite loads than control tadpoles did, and
      they had lower numbers of circulating eosinophilic granulocytes. These results
      provide evidence of glucocorticosteroid-mediated immunosuppression in tadpoles
      that may help to explain apparent increases in the numbers of trematode-induced
      deformities in amphibian populations during recent decades.

PMID- 16108568
TI  - Potential novel epitopes in the extracellular products of oyster homogenate
      supplemented Perkinsus marinus cells are not detected by subtractive
      immunization.
AB  - The extracellular products (ECPs) of the oyster parasite Perkinsus marinus have
      been posed to contain virulence factors, including serine proteases.
      Supplementation of P. marinus cultures with oyster homogenates enhances
      infectivity and changes the ECP composition. Therefore, subtractive immunization
      was used to attempt creation of antibodies to proteins unique to ECPs produced
      following parasite exposure to oyster homogenates. While control mice remained
      competent to respond to an unrelated antigen, no serum titers against novel ECP
      epitopes were detected in experimental mice. Attempts to create discriminatory
      hybridomas resulted in no clones with anti-ECP specificity. These findings
      suggest that, because no unique epitopes can be found within ECPs generated
      following exposure of P. marinus to host homogenates, the changes to ECPs are
      greatly constrained.

PMID- 16108569
TI  - Protein interaction of nucleosome assembly protein 1 and casein kinase 2 during
      desiccation response in the insect-killing nematode Steinernema feltiae IS-6.
AB  - The change in gene expression induced by desiccation in the semiarid,
      entomopathogenic nematode Steinernema feltiae IS-6, includes induction of
      transcription of a nucleosome assembly protein, NAP1 homolog, and of casein
      kinase 2 (CK2) genes. Therefore, one of the events during the dehydration
      response of S. feltiae IS-6 may be transcriptional activation by S. feltiae IS-6
      NAP1 homolog (Sf-Nap1), which is regulated by S. feltiae IS-6 CK2 (Sf-CK2). This
      regulation necessitates physical interaction between the Sf-Nap1 and Sf-CK2
      proteins. In the present study we used yeast 2-hybrid analysis to demonstrate
      physical interaction between the 2 proteins, thus confirming the involvement of a
      protein interaction-based step in the desiccation response mechanism of S.
      feltiae IS-6.

PMID- 16108570
TI  - Prevalence of antibodies to Toxoplasma gondii in raccoons (Procyon lotor) from an
      urban area of Northern Virginia.
AB  - Raccoons (Procyon lotor) are intermediate hosts for Toxoplasma gondii, and
      clinical toxoplasmosis in raccoons has been reported. A 2-yr serological survey
      was conducted to determine the prevalence of antibodies to T. gondii in raccoons
      collected from Fairfax County, Virginia, a suburban/urban area outside
      Washington, D.C. Serum samples from 256 raccoons were examined for T. gondii
      antibodies at a 1:50 dilution using the modified direct agglutination test.
      Results indicated that 216 (84.4%) of the raccoons had been exposed to T. gondii.
      Our results indicate that raccoons in this area of Virginia are frequently
      exposed to T. gondii. Domestic cats were common in the study area and may have
      served as a source of oocysts for raccoons and the food items of raccoons.

PMID- 16108571
TI  - Toxoplasmosis in a Hawaiian monk seal (Monachus schauinslandi).
AB  - Toxoplasma gondii infection in marine mammals is intriguing and indicative of
      contamination of the ocean environment with oocysts. T. gondii was identified in
      a Hawaiian monk seal (Monachus schauinslandi) that had visceral and cerebral
      lesions. Tachyzoites were found in the lymph nodes, spleen, diaphragm, heart,
      adrenal glands, and brain. A few tissue cysts were found in sections of the
      cerebrum. The diagnosis was confirmed serologically, by immunohistochemical
      staining with T. gondii-specific polyclonal rabbit serum, and by the detection of
      T. gondii DNA. The genotype was determined to be type III by restriction fragment
      length polymorphisms of the SAG2 gene. This is the first report of T. gondii
      infection in a Hawaiian monk seal.

PMID- 16108572
TI  - Trematodes associated with mangrove habitat in Puerto Rican salt marshes.
AB  - Batillaria minima is a common snail in the coastal estuaries of Puerto Rico. This
      snail is host to a variety of trematodes, the most common being Cercaria caribbea
      XXXI, a microphallid species that uses crabs as second intermediate hosts. The
      prevalence of infection was higher (7.1%) near mangroves than on mudflats away
      from mangroves (1.4%). Similarly, there was a significant positive association
      between the proportion of a site covered with mangroves and the prevalence of the
      microphallid. The association between mangroves and higher trematode prevalence
      is most likely because birds use mangroves as perch sites and this results in
      local transmission to snails.

PMID- 16108573
TI  - Heat stress-induced modulation of host defense against Toxoplasma gondii
      infection in mice.
AB  - This study examined the effects of burn injury on murine immune response against
      Toxoplasma gondii infection. Male C57BL/6 mice were divided into 3 groups: T.
      gondii infection (group T), burn injury (group B), and burn injury followed by T.
      gondii infection (group BT). The survival of group BT was significantly lower
      than those of group B and group T. Parasite abundance in the tissues was
      determined by quantitative competitive-polymerase chain reaction. Group BT
      exhibited significantly higher numbers of T. gondii than group T. Antibody
      production against T.g.HSP30 in group BT was significantly lower than that in
      group T, whereas no significant difference was observed in SAG1-specific antibody
      production. Delayed-type hypersensitivity (DTH) specific for 2,4
      dinitrofluorobenzene (DNFB) of both group B and group BT was significantly lower
      than that of group T. One week after infection, serum interferon-gamma (IFN
      gamma) and interleukin (IL)-10 levels in group BT were significantly lower,
      whereas serum IL-6 levels were significantly higher than in group T Serum TNF
      alpha levels in both group T and group BT were elevated at 1 wk after infection,
      although there was no significant difference between them. Serum IFN-gamma, IL
      10, and TNF-alpha levels in group B were not elevated during the experimental
      term. In conclusion, the impaired antigen-specific antibody production and DTH
      response, together with the modulated patterns of cytokine responses, seemed to
      be strongly involved in the development of burn-induced immunosuppression and the
      consequent increased susceptibility to T. gondii infection in mice.

PMID- 16108574
TI  - Impact of a caged-trout farm on parasites of Galaxias maculatus in Lake Moreno,
      southern Argentina.
AB  - The present study was conducted to determine the impact of a caged-trout farm on
      the helminth parasites of the wild fish puyen chico (Galaxias maculatus) in Lake
      Moreno, southern Argentina. Samples of water, fish (G. maculatus), and snails
      (Heleobia hatcheri) were taken at 4 sampling stations in January 2001. Wild fish
      were parasitized by 8 helminth species, all of which are endemic in the region;
      therefore, the farm did not introduce any helminth parasite to G. maculatus. Fish
      captured near the farm were not infected by the digenean Steganoderma szidati,
      whereas the abundance of the digenean Acanthostomoides apophalliformis in these
      fish was significantly lower than that in fish captured away from the farm. This
      lower abundance may be explained by the absence in this area of the snail H.
      hatcheri, the parasite's first intermediate host, because of the effect of
      sediments and ammonium produced by the farm. To our knowledge, this is the first
      study in the Americas linking fish-farm pollution to helminth parasites in wild
      fish.

PMID- 16108575
TI  - Multi-species interactions among a commensal (Chaetogaster limnaei limnaei), a
      parasite (Schistosoma mansoni), and an aquatic snail host (Biomphalaria
      glabrata).
AB  - This study assessed the effects of a commensal, Chaetogaster limnaei limnaei, and
      a parasitic trematode, Schistosoma mansoni, on infection patterns and life
      history responses in the aquatic snail Biomphalaria glabrata. Prevalence of
      infection was significantly higher in snails that were devoid of C. limnaei
      limnaei relative to those that were colonized by the commensal, indicating that
      the oligochaete may protect the host from trematode infection. This finding
      appeared to be the direct result of the commensal as opposed to indirect
      stimulation of the immune system, as hemocyte numbers did not differ between C.
      limnaei limnaei-colonized and noncolonized snails. Snail growth and reproduction
      were affected by the presence of C. limnaei limnaei and exposure to S. mansoni.
      Two-way ANOVA revealed a significant effect of both C. limnaei limnaei presence
      and trematode exposure on B. glabrata growth over the 5-wk study with C. limnaei
      limnaei-colonized and parasite-infected snails demonstrating the greatest growth.
      Snails exposed, but uninfected, by S. mansoni demonstrated the lowest growth
      regardless of commensal colonization. Chaetogaster limnaei limnaei colonization
      had no effect on egg production, but S. mansoni-infected snails produced
      significantly more eggs than individuals from other treatment groups. Survival
      remained over 85% in all treatment groups. The ecological implications of these
      results are discussed.

PMID- 16108576
TI  - Genetic characterization of Cryptosporidium isolates from ringed seals (Phoca
      hispida) in Northern Quebec, Canada.
AB  - This study reports the molecular characterization of Cryptosporidium spp.
      isolates identified from intestinal contents of ringed seals (Phoca hispida) from
      Nunavik (Quebec, Canada). Cryptosporidium spp. fragments of 18S rRNA, HSP-70, and
      actin loci were amplified by PCR from seal intestinal contents. PCR-positive
      specimens were sequenced and compared with other Cryptosporidium species and
      genotypes reported previously. Sequence analysis showed the presence of C. muris
      and 2 novel genotypes in ringed seals.

PMID- 16108577
TI  - Fatal Baylisascaris larva migrans in a colony of Japanese macaques kept by a
      safari-style zoo in Japan.
AB  - A colony of Japanese macaques (Macaca fuscata fuscata) kept by a safari-style zoo
      in Japan experienced 9 sporadic cases of fatal neurological diseases, such as
      epilepsy and posterior paralysis, during the 12 yr from 1989 to 2001. This
      macaque colony consisted of approximately 30 animals, on average, during this
      period, and the macaques shared their living space with II American black bears
      (Ursus americanus) harboring zoonotic roundworms (Baylisascaris transfuga). Close
      to this enclosure, a cote for 2-3 raccoons (Procyon lotor) was placed, and raw
      sewage from this cote ran into a shallow drain in the area for macaques and
      bears. However, fecal examinations in recent years did not detect the infection
      of raccoons with zoonotic roundworms (Baylisascaris procyonis). Postmortem
      histological examination of the latest 2 ill macaques detected multifocal malacia
      in the brain; 2 ascarid larvae of 60 microm maximum width were encapsulated in
      the cerebrum and lungs of 1 of the animals. To determine the causative ascarid
      species of the fatal larva migrans, we analyzed 2 additional encapsulated
      Baylisascaris larvae collected from formalin-fixed lungs by morphological and
      molecular approaches. This sporadic outbreak is the second record of
      Baylisascaris larva migrans in animals in Japan.

PMID- 16108578
TI  - Methyl-beta-Cyclodextrin treatment and filipin staining reveal the role of
      cholesterol in surface membrane antigen sequestration of Schistosoma mansoni and
      S. haematobium lung-stage larvae.
AB  - Ex vivo lung-stage larvae of Schistosoma mansoni and S. haematobium do not bind
      specific antibodies in the indirect membrane immunofluorescence test (IF),
      probably as a result of confinement of the surface membrane antigens in immobile,
      lipid-rich sites. Treatment with the membrane-impermeable, cholesterol-extracting
      drug methyl-beta-cyclodextrin (MBCD) and staining with filipin III (filipin), a
      fluorescent polyene antibiotic widely used for the detection and quantitation of
      cholesterol in biomembranes, allowed us to examine the role of cholesterol in
      surface membrane antigen sequestration of S. mansoni and S. haematobium ex vivo
      lung-stage larvae. Treatment of S. mansoni larvae with MBCD elicited appreciable
      cholesterol depletion as judged by filipin-cholesterol fluorescence diminution,
      which was accompanied by a considerable increase in specific antibody binding in
      IF, thus suggesting that cholesterol plays a predominant role in sequestration of
      the surface membrane antigens of S. mansoni lung-stage schistosomula. Despite
      that, MBCD induced an almost complete depletion of cholesterol from the outer
      membrane of S. haematobium larvae; no increase in specific antibody binding in IF
      was evident, implying that cholesterol is not responsible for masking surface
      membrane antigens of S. haematobium lung-stage larvae.

PMID- 16108579
TI  - The genus Atoxoplasma (Garnham 1950) as a junior objective synonym of the genus
      Isospora (Schneider 1881) species infecting birds and resurrection of
      Cystoisospora (Frenkel 1977) as the correct genus for Isospora species infecting
      mammals.
AB  - Molecular and morphological data permit a rational subdivision of the
      paraphyletic Isospora into 2 apparently monophyletic groups of parasites, i.e.,
      Isospora and Cystoisospora. Atoxoplasma was determined to be a junior objective
      synonym for Isospora. Tetrasporozoic, diplosporocystic oocysts possessing Stieda
      bodies in their sporocysts belong to Isospora (Eimeriidae) and have been
      described principally from the feces of birds. Tetrasporozoic, diplosporocystic
      oocysts without Stieda bodies in their sporocysts belong to Cystoisospora
      (Sarcocystidae).

PMID- 16108580
TI  - The manipulation education manual: support for evidence-based education.

PMID- 16108581
TI  - Treatment of cuboid syndrome secondary to lateral ankle sprains: a case series.
AB  - STUDY DESIGN: Case series. BACKGROUND: Plantar flexion/inversion ankle sprains
      are one of the most frequently occurring sports injuries. Cuboid syndrome, which
      is difficult to diagnose, may result from a plantar flexion/ inversion ankle
      injury and could become the source of lateral ankle/midfoot pain. The objective
      of this case series is to describe the examination, evaluation, and treatment of
      the cuboid syndrome following a lateral ankle sprain. CASE DESCRIPTION: Seven
      patients were seen in our clinic 1 to 8 weeks following a lateral ankle sprain
      with a chief complaint of lateral ankle/midfoot pain. In these 7 patients, the
      presence of cuboid syndrome was identified independently by 2 examiners.
      Treatment consisted of a cuboid manipulation. OUTCOMES: All 7 patients returned
      to sports activities following 1 to 2 treatments consisting of the "cuboid whip"
      manipulation. No recurrence of symptoms was reported upon immediate return to
      competition or during the remainder of the season (mean follow-up, 5.7 months;
      range, 2 to 8 months). DISCUSSION: Based on those 7 patients, our results suggest
      that patients who are properly diagnosed with cuboid syndrome and receive the
      cuboid manipulation can return to competitive activity within 1 or 2 visits
      without injury recurrence.

PMID- 16108582
TI  - Thrust joint manipulation clinical education opportunities for professional
      degree physical therapy students.
AB  - STUDY DESIGN: Descriptive survey. OBJECTIVE: Describe the availability of thrust
      joint manipulation clinical educational opportunities for physical therapy
      professional degree students. BACKGROUND: In the United States, most of the
      faculty teaching manual therapy content in physical therapy programs believe that
      the best way for their students to develop thrust joint manipulation skills is to
      receive additional training during clinical education experiences. There are no
      data that describe the availability of such training opportunities. METHODS AND
      MEASURES: Seventy-three physical therapy programs that include thrust joint
      manipulation in their curricula were divided into 5 geographic regions. Of these
      programs, 27% (total, n = 20) were randomly selected per region to participate.
      Program academic coordinators of clinical education (ACCEs) identified their
      clinical instructors working in outpatient orthopaedic settings. ACCEs and
      clinical instructors were surveyed regarding thrust joint manipulation clinical
      education opportunities for students. RESULTS: Survey return rates were 100% for
      ACCEs and 67.4% for clinical instructors. Of ACCEs, 70% were unsure which sites
      employed clinical instructors trained in thrust joint manipulation and 85% did
      not consider whether thrust joint manipulation training was provided when
      scheduling the experience. The ACCEs who did consider availability cited lack of
      qualified instructors as the number-one barrier to finding sites that offered
      thrust joint manipulation. Of clinical instructors, 30% provide thrust joint
      manipulation training including lecture/theory, technique demonstration, practice
      on "normals," and direct patient care supervision. Clinical instructors who did
      not teach thrust joint manipulation cited reasons that included the belief that
      it is not an entry-level skill (57%), lack of qualified staff (53%), liability
      concerns (46%), and students not being academically prepared (41%). CONCLUSIONS:
      Results suggest that the availability and scope of thrust joint manipulation
      clinical educational opportunities are limited, vary considerably, and are not
      considered when selecting clinical education sites for students. Potential
      obstacles to offering thrust joint manipulation training were identified, which
      suggested the need for resources, including clinical education curricula and
      philosophical guidelines for clinical instructors.

PMID- 16108583
TI  - Quadriceps strength and the time course of functional recovery after total knee
      arthroplasty.
AB  - STUDY DESIGN: Prospective study with repeated measures. OBJECTIVES: The overall
      goal of this investigation was to describe the time course of recovery of
      impairments and function after total knee arthroplasty (TKA), as well as to
      provide direction for rehabilitation efforts. We hypothesized that quadriceps
      strength would be more strongly correlated with functional performance than knee
      flexion range of motion (ROM) or pain at all time periods studied before and
      after TKA. BACKGROUND: TKA is a very common surgery, but very little is known
      regarding the influence of impairments on functional limitations in this
      population. METHODS AND MEASURES: Forty subjects who underwent unilateral TKA
      followed by rehabilitation, including 6 weeks of outpatient physical therapy,
      were studied. Testing occurred at 5 time periods: preoperatively, and at 1, 2, 3,
      and 6 months after surgery. Test measures included quadriceps strength, knee ROM,
      timed up-and-go test, timed stair-climbing test, bodily pain, and general health
      and knee function questionnaires. RESULTS: Subjects experienced significant
      worsening of knee ROM, quadriceps strength, and performance on functional tests 1
      month after surgery. Quadriceps strength went through the greatest decline of all
      the physical measures assessed and never matched the strength of the uninvolved
      limb. All measures underwent significant improvements following the 1-month test.
      Quadriceps strength was the most highly correlated measure associated with
      functional performance at all testing sessions. CONCLUSIONS: Functional measures
      underwent an expected decline early after TKA, but recovery was more rapid than
      anticipated and long-term outcomes were better than previously reported in the
      literature. The high correlation between quadriceps strength and functional
      performance suggests that improved postoperative quadriceps strengthening could
      be important to enhance the potential benefits of TKA.

PMID- 16108584
TI  - Isometric back extension endurance testing: reasons for test termination.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: The self-reported reasons for
      terminating isometric back extension endurance testing and their associations
      with test performance and other factors were investigated to gain insight into
      determinants of test performance. BACKGROUND: Factors limiting isometric back
      extension endurance performance remain unclear. Better understanding the reasons
      for termination of isometric extension endurance testing could provide insights
      into what the test actually reflects. METHODS AND MEASURES: Lifetime work,
      leisure activities and back pain questionnaire data, isometric back extension
      endurance testing (holding time, as measured in seconds), and reasons for test
      termination were obtained for a population-based sample of 544 working-age men.
      RESULTS: The most common reason for test termination was fatigue (62.5%),
      followed by pain in various parts of the lower extremities (12.6%) and back
      (3.2%). A history of daily low back pain over the prior 12 months and greater
      pain intensity of the worst back pain episode over the same period were
      associated with a greater likelihood of termination due to back pain. In a
      regression analysis, longer holding time was associated with stopping due to
      fatigue rather than low back pain, with a trend of 19 seconds (95% confidence
      interval [CI], -2-40) longer holding time. After controlling for low back pain
      history, those previously involved in competitive sports were 2.6 times more
      likely to stop due to pain. Those with a competitive sport history had 14 seconds
      (95% CI, 5-23) greater holding time than those without such a history.
      CONCLUSIONS: Isometric back extension endurance testing is most commonly reported
      to be terminated due to muscle-related capacity as indicated by fatigue. Back
      pain is more likely to decrease performance time in men with a history of
      significant (frequent, intense) low back symptoms.

PMID- 16108585
TI  - Sustained muscle activity minimally influences dynamic position sense of the
      ankle.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: The purpose of this study was to
      determine if a sustained fatiguing contraction of the dorsiflexor muscles alters
      the dynamic position sense (proprioception) and the associated central nervous
      system processing time of information from the ankle. BACKGROUND: Ankle injury
      has been hypothesized to be related to altered proprioception as a consequence of
      fatiguing exercise. Previous reports assessing proprioception include tests of
      motor performance (balance and limb repositioning) or tests of a joint under
      static conditions. This study used a novel experimental approach to test the
      effects of exercise on the somatosensory system of the ankle. METHODS AND
      MEASURES: Nineteen healthy subjects were tested on their ability to extend the
      metacarpophalangeal joint of their left index finger when their left ankle was
      passively plantar flexed (0 degrees-40 degrees, 10 velocities) through a
      predetermined target angle (20 degrees). Testing occurred before and after a
      fatiguing contraction of the dorsiflexor muscles. RESULTS: Subjects accurately
      indicated the ankle target angle up to ankle velocities of 70 degrees/s (300 ms)
      both before and after the sustained fatiguing contraction. At velocities above 70
      degrees/s all subjects could no longer scale to accurately indicate the target
      angle with the index finger and consequently overshot the target. The central
      nervous system processing time was estimated to be approximately 85 milliseconds
      before and after the sustained contraction. CONCLUSIONS: These results indicate
      that a sustained activity of the dorsiflexion muscles of the ankle minimally
      affects dynamic position sense and the ability to process dynamic position sense
      information. Understanding the impact of exercise on sensory system processing
      will be integral to establishing the scientific basis for rehabilitation programs
      that purport to train proprioception.

PMID- 16108586
TI  - The relationship of intrinsic fall risk factors to a recent history of falling in
      older women with osteoporosis.
AB  - STUDY DESIGN: Cross-sectional descriptive analysis investigating intrinsic fall
      risk factors in postmenopausal women with osteoporosis. OBJECTIVE: To examine the
      relationships between history of recent falls and balance, pain, quality of life,
      function, posture, strength, and mobility. BACKGROUND: Women with osteoporosis
      who fall are at a high risk of fracture due to decreased bone strength.
      Identifying fall risk factors for older women with osteoporosis is a crucial step
      in decreasing the incidence of falls and fracture. METHOD AND MEASURES: Seventy
      three women over 60 years of age with established osteoporosis participated in
      comprehensive testing of fall history, physical function, and quality of life.
      RESULTS: Significant correlations were found between a recent history of falls
      and degree of kyphosis (r = 0.29), fear of falls/emotional status (r = -0.27),
      and balance (r = -0.27). Degree of kyphosis and fear of falls/emotional status
      explained 20% of the variance of recent fall history using binary logistic
      regression. Women with an increased kyphosis were more likely to have had a
      recent fall (odds ratio [OR], 1.17; 95% CI, 1.03-1.34) and those with better
      emotional status and less fear of falling were less likely to have had a recent
      fall (OR, 0.61; 95% CI, 0.38-0.97). CONCLUSION: Increased thoracic kyphosis and
      fear of falling are 2 intrinsic factors associated with recent falls in women
      with osteoporosis. To design more effective interventions to decrease fall risk
      in this population, future prospective, longitudinal studies should monitor
      kyphosis, fear of falling, balance reactions, and other potential risk factors
      not identified in this study.

PMID- 16108587
TI  - [Roxithromycin suppresses expression of mucin gene MUC2 in cultured epithelial
      cells].

PMID- 16108588
TI  - [Analysis of the mechanism of suppression on MUC5AC by macrolides--an analysis by
      using a chronic airway infection model].

PMID- 16108589
TI  - [Effect of macrolides on matrix protein decomposing enzyme (MMP) production].

PMID- 16108590
TI  - [Effects of clarithromycin on a rat endometriosis model: light and electron
      microscopic evaluation].

PMID- 16108591
TI  - [Evaluation of anti-inflammatory effect of macrolides on macrophages].

PMID- 16108592
TI  - [Inhibitory effects of macrolides on exaggerated production of vascular
      endothelial growth factor (VEGF) caused by co-stimulation by hypoxia and TNF
      alpha].

PMID- 16108593
TI  - [Current viewpoint on macrolides].

PMID- 16108594
TI  - [Research on new macrolide actions in the past 10 years--from the viewpoint of
      clinical practice].

PMID- 16108595
TI  - [Summary of research activities on new actions of macrolides in the past 10 years
      -a view form the host].

PMID- 16108597
TI  - [Overview on future studies on macrolide actions--from the host viewpoint].

PMID- 16108596
TI  - [Macrolide research in the past 10 years--modulation of bacterial functions].

PMID- 16108598
TI  - [Modulation of bacterial pathogenic factors by macrolides--past understanding and
      the future prospect].

PMID- 16108599
TI  - [Macrolides and neutrophilic apoptosis clearance in chronic airway infections].

PMID- 16108600
TI  - [The mechanism of apoptosis induction in lymphocytes by macrolide antibiotics and
      the related intra-cellular molecular structure].

PMID- 16108601
TI  - [Erythromycin intensifies Toll-like receptor 2 expression on dendritic cells].

PMID- 16108602
TI  - [Effects of EM201, an in vivo metabolite of erythromycin, on differentiation and
      functions of dendrite cells].

PMID- 16108603
TI  - [Analysis of the granuloma forming mechanism captured in diverse immunocompetent
      cell dynamics].

PMID- 16108604
TI  - [Effects of roxithromycin on a guinea pig model for chronic asthma].

PMID- 16108605
TI  - [Inhibitory effects of various macrolide antibiotics on nitric oxide (NO)
      production--a study using mice treated with small amounts of antibiotics for an
      extended period].

PMID- 16108606
TI  - [Mechanism for an anti-inflammatory action of macrolide in the epidermal cells].

PMID- 16108607
TI  - [Involvement of hnRNP in selective translation inhibition of mRNA by rapamycin].

PMID- 16108608
TI  - [Effect of EM201, an in vivo metabolite of erythromycin (EM), on signal
      transduction of IL-2 receptor].

PMID- 16108609
TI  - [Analysis of the mechanism of anti-mycotic activities by azoles potentiated by
      new erythromycin derivatives].

PMID- 16108610
TI  - [Analysis of gene expression of erythromycin-treated, activated human monocytes
      by employing the Long SAGE method].

PMID- 16108611
TI  - [System biological medicine and treatment of vascular diseases].

PMID- 16108612
TI  - [Creation of a new macrolide derivative, EM703].

PMID- 16108613
TI  - [Effect of EM703, a new macrolide derivative, on activation of transcription
      factors derived from the airway epithelial cells].

PMID- 16108614
TI  - [Effect of EM703, a new macrolide derivative, on mucus secretion from the airway
      epithelial cells].

PMID- 16108615
TI  - [Action of EM703, a new macrolide derivative, on the lung that has been damaged
      by influenza virus].

PMID- 16108616
TI  - [Action of EM703 on bleomycin-induced pulmonary fibrosis in mice].

PMID- 16108617
TI  - Two photoionization thresholds of N3 produced by ClN3 photodissociation at 248
      nm: further evidence for cyclic N3.
AB  - We present results of near-threshold photoionization of N3 photofragments
      produced by laser photodissociation of ClN3 at 248 nm. The time of flight of
      recoiling N3 is used to resolve two photochemical channels producing N3, which
      exhibit different translational energy release. The two forms of N3 resolved in
      this way exhibit different photoionization thresholds, consistent with their
      assignment to linear (X 2pi(g)) and cyclic N3. This result agrees with the
      existing theoretical calculations of excited and ionic states of N3 and
      strengthens previous experimental results which suggested that the ClN3
      photolysis produces a cyclic form of N3.

PMID- 16108618
TI  - The surprisingly short vibrational lifetime of the internal stretch of CO
      adsorbed on Si(100).
AB  - Picosecond sum-frequency generation spectroscopy has been employed to study the
      dynamics of the internal stretch vibration of CO adsorbed on a Si(100) surface.
      Using the IR pump-sum-frequency generation probe method, the vibrational lifetime
      of the C-O stretch vibration has been determined to be 2.3+/-0.5 ns. Within the
      experimental error limits, the identical lifetime was observed for 12C16O and
      13C16O. No strong dependency on the carrier density in the substrate, inferred
      from measurements using differently doped crystals, was observed.

PMID- 16108619
TI  - Magnetoresistance devices based on single-walled carbon nanotubes.
AB  - We demonstrate the physical principles for the construction of a nanometer-sized
      magnetoresistance device based on the Aharonov-Bohm effect [Phys. Rev. 115, 485
      (1959)]. The proposed device is made of a short single-walled carbon nanotube
      (SWCNT) placed on a substrate and coupled to a tip/contacts. We consider
      conductance due to the motion of electrons along the circumference of the tube
      (as opposed to the motion parallel to its axis). We find that the circumference
      conductance is sensitive to magnetic fields threading the SWCNT due to the
      Aharonov-Bohm effect, and show that by retracting the tip/contacts, so that the
      coupling to the SWCNT is reduced, very high sensitivity to the threading magnetic
      field develops. This is due to the formation of a narrow resonance through which
      the tunneling current flows. Using a bias potential the resonance can be shifted
      to low magnetic fields, allowing the control of conductance with magnetic fields
      of the order of 1 T.

PMID- 16108620
TI  - Endothermic freezing on heating and exothermic melting on cooling.
AB  - Generally, a liquid freezes exothermally on cooling and a crystal melts
      endothermally on heating. Here we report an opposite occurrence--a liquid's
      endothermic freezing on heating and the resulting crystal's exothermic melting on
      cooling at ambient pressures. C(p) decreases on freezing and increases on
      melting, and the equilibrium temperature meets the thermodynamic requirement.
      Melting on cooling takes longer than freezing on heating. A rapidly cooled
      crystal state becomes kinetically frozen, evocative of a nonergodic state. Both
      C(p) and enthalpy relax like those of glasses, though the viscosity is only a few
      centipoise. The crystal state belongs to energy minima higher than those of the
      melt, which has consequences for the use of potential-energy landscape, or
      inherent structures, for a thermodynamic description of a material.

PMID- 16108621
TI  - Three-photon near-threshold photoionization dynamics of isooctane.
AB  - The electron survival probability following three-photon (9.3 eV total) near
      threshold photoionization of neat isooctane is measured with sub-50 fs time
      resolution. The measured dynamics are nonexponential in time and are well
      described by a diffusion-controlled electron-cation recombination model.
      Excitation-power-dependent studies indicate that the unperturbed three-photon
      threshold ionization is only observed for pump irradiance below 0.5 TW cm2. At
      excitation fields above this level, the signal is no longer cubic in the
      excitation irradiance, and the observed electron survival probability
      dramatically changes, decaying as a single exponential in time.

PMID- 16108622
TI  - Vibrational cooling in a cold ion trap: vibrationally resolved photoelectron
      spectroscopy of cold C60(-) anions.
AB  - We demonstrate vibrational cooling of anions via collisions with a background gas
      in an ion trap attached to a cryogenically controlled cold head (10-400 K).
      Photoelectron spectra of vibrationally cold C60(-) anions, produced by
      electrospray ionization and cooled in the cold ion trap, have been obtained.
      Relative to spectra taken at room temperature, vibrational hot bands are
      completely eliminated, yielding well-resolved vibrational structures and a more
      accurate electron affinity for neutral C60. The electron affinity of C60 is
      measured to be 2.683+/-0.008 eV. The cold spectra reveal complicated vibrational
      structures for the transition to the C60 ground state due to the Jahn-Teller
      effect in the ground state of C60(-). Vibrational excitations in the two A(g)
      modes and eight H(g) modes are observed, providing ideal data to assess the
      vibronic couplings in C60(-).

PMID- 16108623
TI  - NMR shielding constants for hydrogen guest molecules in structure II clathrates.
AB  - Proton NMR shielding constants and chemical shifts for hydrogen guests in small
      and large cages of structure II clathrates are calculated using density
      functional theory and the gauge-invariant atomic-orbital method. Shielding
      constants are calculated at the B3LYP level with the 6-311++G(d,p) basis set. The
      calculated chemical shifts are corrected with a linear regression to reproduce
      the experimental chemical shifts of a set of standard molecules. The calculated
      chemical shifts of single hydrogen molecules in the small and large structure II
      cages are 4.94 and 4.84 ppm, respectively, which show that within the error range
      of the method the H2 guest molecules in the small and large cages cannot be
      distinguished. Chemical shifts are also calculated for double occupancy of the
      hydrogen guests in small cages, and double, triple, and quadruple occupancy in
      large cages. Multiple occupancy changes the chemical shift of the hydrogen guests
      by approximately 0.2 ppm. The relative effects of other guest molecules and the
      cage on the chemical shift are studied for the cages with multiple occupancies.

PMID- 16108624
TI  - A new molecular-dynamics based approach for molecular crystal structure search.
AB  - A new molecular-dynamics based approach is proposed to search for candidate
      crystal structures of molecular solids. The procedure is based on the observation
      of spontaneous transitions between ordered and disordered states in molecular
      dynamics simulations of an artificial periodic system with a small unit cell. In
      such a way only the most stable structures are automatically selected. The method
      can be applied to the solution of crystal structures from low-quality or very
      complex diffraction data. Tests are presented for H2O-ice polymorphs.

PMID- 16108625
TI  - Coupled-cluster methods including noniterative corrections for quadruple
      excitations.
AB  - A new method is presented for treating the effects of quadruple excitations in
      coupled-cluster theory. In the approach, quadruple excitation contributions are
      computed from a formula based on a non-Hermitian perturbation theory analogous to
      that used previously to justify the usual noniterative triples correction used in
      the coupled cluster singles and doubles method with a perturbative treatment of
      the triple excitations (CCSD(T)). The method discussed in this paper plays a
      parallel role in improving energies obtained with the full coupled-cluster
      singles, doubles, and triples method (CCSDT) by adding a perturbative treatment
      of the quadruple excitations (CCSDT(Q)). The method is tested for an extensive
      set of examples, and is shown to provide total energies that compare favorably
      with those obtained with the full singles, doubles, triples, and quadruples
      (CCSDTQ) method.

PMID- 16108626
TI  - Time-dependent four-component relativistic density-functional theory for
      excitation energies. II. The exchange-correlation kernel.
AB  - We extend our previous formulation of time-dependent four-component relativistic
      density-functional theory [J. Gao, W. Liu, B. Song, and C. Liu, J. Chem. Phys.
      121, 6658 (2004)] by using a noncollinear form for the exchange-correlation
      kernel. The new formalism can deal with excited states involving moment (spin)
      flipped configurations which are otherwise not accessible with ordinary exchange
      correlation functionals. As a first application, the global potential-energy
      curves of 16 low-lying omega omega-coupled electronic states of the AuH molecule
      have been investigated. The derived spectroscopic parameters, including the
      adiabatic and vertical excitation energies, equilibrium bond lengths, harmonic
      and anharmonic vibrational constants, fundamental frequencies, and dissociation
      energies, are grossly in good agreement with those of ab initio multireference
      second-order perturbation theory and the available experimental data.

PMID- 16108627
TI  - Phase-space overlap measures. I. Fail-safe bias detection in free energies
      calculated by molecular simulation.
AB  - We consider ways to quantify the overlap of the parts of phase space important to
      two systems, labeled A and B. Of interest is how much of the A-important phase
      space lies in that important to B, and how much of B lies in A. Two measures are
      proposed. The first considers four total-energy distributions, formed from all
      combinations made by tabulating either the A-system or the B-system energy when
      sampling either the A or B system. Measures for A in B and B in A are given by
      two overlap integrals defined on pairs of these distributions. The second measure
      is based on information theory, and defines two relative entropies which are
      conveniently expressed in terms of the dissipated work for free-energy
      perturbation (FEP) calculations in the A-->B and B-->A directions, respectively.
      Phase-space overlap is an important consideration in the performance of free
      energy calculations. To demonstrate this connection, we examine bias in FEP
      calculations applied to a system of independent particles in a harmonic
      potential. Systems are selected to represent a range of overlap situations,
      including extreme subset, subset, partial overlap, and nonoverlap. The magnitude
      and symmetry of the bias (A-->B vs B-->A) are shown to correlate well with the
      overlap, and consequently with the overlap measures. The relative entropies are
      used to scale the amount of sampling to obtain a universal bias curve. This
      result leads to develop a simple heuristic that can be applied to determine
      whether a work-based free-energy measurement is free of bias. The heuristic is
      based in part on the measured free energy, but we argue that it is fail-safe
      inasmuch as any bias in the measurement will not promote a false indication of
      accuracy.

PMID- 16108628
TI  - Avoiding negative populations in explicit Poisson tau-leaping.
AB  - The explicit tau-leaping procedure attempts to speed up the stochastic simulation
      of a chemically reacting system by approximating the number of firings of each
      reaction channel during a chosen time increment tau as a Poisson random variable.
      Since the Poisson random variable can have arbitrarily large sample values, there
      is always the possibility that this procedure will cause one or more reaction
      channels to fire so many times during tau that the population of some reactant
      species will be driven negative. Two recent papers have shown how that
      unacceptable occurrence can be avoided by replacing the Poisson random variables
      with binomial random variables, whose values are naturally bounded. This paper
      describes a modified Poisson tau-leaping procedure that also avoids negative
      populations, but is easier to implement than the binomial procedure. The new
      Poisson procedure also introduces a second control parameter, whose value
      essentially dials the procedure from the original Poisson tau-leaping at one
      extreme to the exact stochastic simulation algorithm at the other; therefore, the
      modified Poisson procedure will generally be more accurate than the original
      Poisson procedure.

PMID- 16108629
TI  - Determination of the chemical potential using energy-biased sampling.
AB  - An energy-biased method to evaluate ensemble averages requiring test-particle
      insertion is presented. The method is based on biasing the sampling within the
      subdomains of the test-particle configurational space with energies smaller than
      a given value freely assigned. These energy wells are located via unbiased random
      insertion over the whole configurational space and are sampled using the so
      called Hit-and-Run algorithm, which uniformly samples compact regions of any
      shape immersed in a space of arbitrary dimensions. Because the bias is defined in
      terms of the energy landscape it can be exactly corrected to obtain the unbiased
      distribution. The test-particle energy distribution is then combined with the
      Bennett relation for the evaluation of the chemical potential. We apply this
      protocol to a system with relatively small probability of low-energy test
      particle insertion, liquid argon at high density and low temperature, and show
      that the energy-biased Bennett method is around five times more efficient than
      the standard Bennett method. A similar performance gain is observed in the
      reconstruction of the energy distribution.

PMID- 16108630
TI  - A Jacobi-Wilson description coupled to a block-Davidson algorithm: an efficient
      scheme to calculate highly excited vibrational levels.
AB  - We present a new approach based on the block-Davidson scheme which provides
      eigenvalues and eigenvectors of highly excited (ro) vibrational states of
      polyatomic molecules. The key ingredient is a prediagonalized-perturbative scheme
      applied to a subspace of a curvilinear normal-mode basis set. This approach is
      coupled to the Jacobi vector description recently developed by our group [C.
      Leforestier, A. Viel, F. Gatti, C. Munoz, and C. Iung, J. Chem. Phys. 114, 2099
      (2001)], and applied to the HFCO and H2CO molecules, which represent the main
      difficulties of such calculations for any available method. The first one
      presents a significant state density because of its low symmetry and the presence
      of a fluorine atom, while strong resonances and intermode couplings occur in
      H2CO. This study establishes the robustness, the numerical efficiency, and the
      versatility of the method which is compared to the regular Lanczos and Davidson
      schemes. It is also shown that the eigenvectors can be obtained within a given
      accuracy easily set by the user. This point constitutes one of the main
      advantages of the method as very few potential-energy surfaces achieve an
      accuracy of the order of a wave number for highly excited states. Furthermore,
      this method allows one to restrict the calculations to selected energy levels
      based on their zero-order descriptions.

PMID- 16108631
TI  - Quantum hydrodynamics: capturing a reactive scattering resonance.
AB  - The hydrodynamic equations of motion associated with the de Broglie-Bohm
      formulation of quantum mechanics are solved using a meshless method based upon a
      moving least-squares approach. An arbitrary Lagrangian-Eulerian frame of
      reference and a regridding algorithm which adds and deletes computational points
      are used to maintain a uniform and nearly constant interparticle spacing. The
      methodology also uses averaged fields to maintain unitary time evolution. The
      numerical instabilities associated with the formation of nodes in the reflected
      portion of the wave packet are avoided by adding artificial viscosity to the
      equations of motion. A new and more robust artificial viscosity algorithm is
      presented which gives accurate scattering results and is capable of capturing
      quantum resonances. The methodology is applied to a one-dimensional model
      chemical reaction that is known to exhibit a quantum resonance. The correlation
      function approach is used to compute the reactive scattering matrix, reaction
      probability, and time delay as a function of energy. Excellent agreement is
      obtained between the scattering results based upon the quantum hydrodynamic
      approach and those based upon standard quantum mechanics. This is the first clear
      demonstration of the ability of moving grid approaches to accurately and robustly
      reproduce resonance structures in a scattering system.

PMID- 16108632
TI  - Quantum-instanton evaluation of the kinetic isotope effects.
AB  - A general quantum-mechanical method for computing kinetic isotope effects is
      presented. The method is based on the quantum-instanton approximation for the
      rate constant and on the path-integral Metropolis-Monte Carlo evaluation of the
      Boltzmann operator matrix elements. It computes the kinetic isotope effect
      directly, using a thermodynamic integration with respect to the mass of the
      isotope, thus avoiding the more computationally expensive process of computing
      the individual rate constants. The method should be more accurate than
      variational transition-state theories or the semiclassical instanton method since
      it does not assume a single tunneling path and does not use a semiclassical
      approximation of the Boltzmann operator. While the general Monte Carlo
      implementation makes the method accessible to systems with a large number of
      atoms, we present numerical results for the Eckart barrier and for the collinear
      and full three-dimensional isotope variants of the hydrogen exchange reaction H +
      H2 --> H2 + H. In all seven test cases, for temperatures between 250 and 600 K,
      the error of the quantum instanton approximation for the kinetic isotope effects
      is less than approximately 10%.

PMID- 16108633
TI  - Photodissociation of HI and DI: testing models for electronic structure via
      polarization of atomic photofragments.
AB  - The photodissociation dynamics of HI and DI are examined using time-dependent
      wave-packet techniques. The orientation and alignment parameters aQ(K) (p) are
      determined as a function of photolysis energy for the resulting ground-state
      I(2P(3/2)) and excited-state I(2P(1/2)) atoms. The aQ(K) (p) parameters describe
      the coherent and incoherent contributions to the angular momentum distributions
      from the A 1pi(1), a 3pi(1), and t 3sigma(1) electronic states accessed by
      perpendicular excitation and the a 3pi(0+) state accessed by a parallel
      transition. The outcomes of the dynamics based on both shifted ab initio results
      and three empirical models for the potential-energy curves and transition dipole
      moments are compared and contrasted. It is demonstrated that experimental
      measurement of the aQ(K) (p) parameters for the excitation from the vibrational
      ground state (upsilon=0) would be able to distinguish between the available
      models for the HI potential-energy curves and transition dipole moments. The
      differences between the aQ(K) (p) parameters for the excitation from upsilon=0
      stand in sharp contrast to the scalar properties, i.e., total cross section and
      I* branching fraction, which require experimental measurement of
      photodissociation from excited vibrational states (upsilon>0) to distinguish
      between the models.

PMID- 16108634
TI  - High-level ab initio studies of the structure, vibrational spectra, and
      energetics of S3.
AB  - Observation of mass-dependent and non-mass-dependent sulfur isotope
      fractionations in elemental sulfur is providing new insight into the nature of
      the sulfur cycle in the atmosphere. Interpretation of the experimental isotope
      data requires estimation of the energetics for the reaction S+S2-->S3
      (isoelectronic with O+O2-->O3). Key molecular properties of the S3 potential
      energy surface, such as vibrational frequencies and isotopic shifts, are
      presented that can be used to assess the mass-dependent fractionation effect. Ab
      initio results are compared to the available experimental results for S2 to
      evaluate the reliability of the computational results for S3. The S-S bond
      dissociation energy for S3 is determined to be 60.9+/-1 kcal mol(-1).

PMID- 16108635
TI  - Experimental and modeling study of the ion-molecule association reaction H3O+ +
      H2O (+M) --> H5O2(+) (+M).
AB  - Experimental results for the rate of the association reaction H3O+ + H2O (+M) -->
      H5O2(+) (+M) obtained with the Cinetique de Reactions en Ecoulement Supersonique
      Uniforme flow technique are reported. The reaction was studied in the bath gases
      M=He and N2, over the temperature range of 23-170 K, and at pressures between
      0.16 and 3.1 mbar. At the highest temperatures, the reaction was found to be
      close to the limiting low-pressure termolecular range, whereas the limiting high
      pressure bimolecular range was approached at the lowest temperatures. Whereas the
      low-pressure rate coefficients can satisfactorily be reproduced by standard
      unimolecular rate theory, the derived high-pressure rate coefficients in the bath
      gas He at the lowest temperatures are found to be markedly smaller than given by
      simple ion-dipole capture theory. This result differs from previous observations
      on the related reaction NH4(+) + NH3 (+M) --> N2H7(+) (+M). This observation is
      tentatively attributed to more pronounced contributions of the valence part of
      the potential-energy surface to the reaction in H5O2(+) than in N2H7(+). Falloff
      curves of the reaction H3O+ + H2O (+M) --> H5O2(+) (+M) are constructed over wide
      ranges of conditions and represented in compact analytical form.

PMID- 16108636
TI  - Spectroscopic and theoretical characterization of the A2delta-X2pi transition of
      CH-Ne.
AB  - The A2delta-X2pi transition of CH-Ne was examined using laser-induced
      fluorescence and fluorescence depletion techniques. The spectrum was found to be
      particularly congested due to the large number of bound states derived from the
      CH(A,n=2)+Ne interaction, and the small energy spacings between these states
      resulting from the relatively weak anisotropy of the van der Waals bond. High
      level ab initio calculations were used to generate two-dimensional potential
      energy surfaces for CH(X)-Ne and CH(A)-Ne. The equilibrium structures from these
      surfaces were bent and linear for the X and A states, respectively. Variational
      calculations were used to predict the bound states supported by the ab initio
      surfaces. Empirical modification of the potential energy surfaces for the A state
      was used to obtain energy-level predictions that were in good agreement with the
      experimental results. Transitions to all of the optically accessible internal
      rotor states of CH(A,n=2)-Ne were identified, indicating that CH performs
      hindered internal rotations in the lowest-energy levels of the A and X states.
      The characteristics of the potential energy surfaces for CH-Ne in the X,A,B, and
      C states suggest that dispersion and exchange repulsion forces dominate the van
      der Waals interaction.

PMID- 16108637
TI  - Ar(n)HF van der Waals clusters revisited: II. Energetics and HF vibrational
      frequency shifts from diffusion Monte Carlo calculations on additive and
      nonadditive potential-energy surfaces for n=1-12.
AB  - The ground-state energies and HF vibrational frequency shifts of Ar(n)HF clusters
      have been calculated on the nonadditive potential-energy surfaces (PESs) for n=2
      7 and on the pairwise-additive PESs for the clusters with n=1-12, using the
      diffusion Monte Carlo (DMC) method. For n>3, the calculations have been performed
      for the lowest-energy isomer and several higher-lying isomers which are the
      closest in energy. They provide information about the isomer dependence of the HF
      redshift, and enable direct comparison with the experimental data recently
      obtained in helium nanodroplets. The agreement between theory and experiment is
      excellent, in particular, for the nonadditive DMC redshifts. The relative,
      incremental redshifts are reproduced accurately even at the lower level of
      theory, i.e., the DMC and quantum five-dimensional (rigid Ar(n)) calculations on
      the pairwise-additive PESs. The nonadditive interactions make a significant
      contribution to the frequency shift, on the order of 10%-12%, and have to be
      included in the PESs in order for the theory to yield accurate magnitude of the
      HF redshift. The energy gaps between the DMC ground states of the cluster isomers
      are very different from the energy separation of their respective minima on the
      PES, due to the considerable variations in the intermolecular zero-point energy
      of different Ar(n)HF isomers.

PMID- 16108638
TI  - Collision-energy dependence of HD(nu'=1,j') product rotational distributions for
      the H + D2 reaction.
AB  - Product rotational distributions for the reaction H + D2 --> HD(nu'=1,j') + D
      have been measured for 16 collision energies in the range of 1.43 < or = E(coll)
      < or = 2.55 eV. Time-dependent quantum-mechanical calculations agree well in
      general with the experimental results, but they consistently yield slightly
      colder distributions. In terms of the average energy channeled into rotation, the
      differences between experiment and theory amount to approximately 10% for all
      collision energies sampled. No peculiarity is found for E(coll)=2.55 eV at which
      the system has sufficient energy to access the first HD2 electronically excited
      state.

PMID- 16108639
TI  - Multiple solvation configurations around phthalocyanine in helium droplets.
AB  - Recent measurements of the emission spectrum of phthalocyanine solvated in
      superfluid helium nanodroplets exhibit a constant 10.3 cm(-1) splitting of each
      emission line relative to the absorption spectrum. This splitting has been
      attributed to two distinct helium environments near the surface of the
      phthalocyanine molecule. Rigid-body path-integral Monte Carlo provides a means of
      investigating the origin of the splitting on a detailed microscopic level. Path
      integral Monte Carlo simulations of 4He(N)-phthalocyanine at 0.625 K with N
      ranging from 24 to 150 show two distinct helium configurations. One configuration
      is commensurate with the molecular substrate and the other is a triangular
      lattice. We investigate the energetics of these two configurations and use a
      method for calculating electronic spectral shifts for aromatic molecule-rare-gas
      clusters due to dispersive interactions to estimate the spectral splitting that
      would arise from the two helium configurations seen for N=150. The results are in
      reasonable agreement with the experimentally measured splitting, supporting the
      existence of two distinct local helium environments near the surface of the
      molecule in the nanodroplets.

PMID- 16108640
TI  - Femtosecond degenerate four-wave mixing of cyclopropane.
AB  - Femtosecond degenerate four-wave mixing (fs-DFWM) is applied for the measurement
      of rotational constants of cyclopropane (C3H6). The rotational coherence method
      yields a very accurate B0 = 20,093.322(12) MHz and centrifugal distortion
      constants D(J) and D(JK). To exploit the full resolution of the fs-DFWM method,
      the accuracy of the optical delay measurement was increased by nearly two orders
      of magnitude, including elimination of effects from the refractive index of air.
      The fs-DFWM molecular constants are comparable in accuracy to those from high
      resolution infrared spectroscopy and are only surpassed by those of dipole
      distortion microwave spectroscopy. In parallel, the equilibrium structure,
      vibrationally averaged structure parameters and rotational constants were
      calculated using high-level ab initio methods and large basis sets. Combining
      these with the results of previous calculations and the measured rotational
      constants yields r(e)(C-C) = 1.5034(3) A, r(e)(C-H) = 1.0775(5) A, and alpha(e)(H
      C-H) = 115.09(10) degrees.

PMID- 16108641
TI  - Photodissociation dynamics of pyridine.
AB  - Photodissociation of pyridine, 2,6-d2-pyridine, and d5-pyridine at 193 and 248 nm
      was investigated separately using multimass ion imaging techniques. Six
      dissociation channels were observed at 193 nm, including C5NH5 --> C5NH4 + H
      (10%) and five ring opening dissociation channels, C5NH5 --> C4H4 + HCN, C5NH5 -
      > C3H3 + C2NH2, C5NH5 --> C2H4 +C3NH, C5NH5 --> C4NH2 + CH3 (14%), and C5NH5 -->
      C2H2 + C3NH3. Extensive H and D atom exchanges of 2,6-d2-pyridine prior to
      dissociation were observed. Photofragment translational energy distributions and
      dissociation rates indicate that dissociation occurs in the ground electronic
      state after internal conversion. The dissociation rate of pyridine excited by 248
      nm photons was too slow to be measured, and the upper limit of the dissociation
      rate was estimated to be 2x10(3) s(-1). Comparisons with potential energies
      obtained from ab initio calculations and dissociation rates obtained from the
      Rice-Ramsperger-Kassel-Marcus theory have been made.

PMID- 16108642
TI  - The electronic structure of free water clusters probed by Auger electron
      spectroscopy.
AB  - (H2O)(N) clusters generated in a supersonic expansion source with N approximately
      1000 were core ionized by synchrotron radiation, giving rise to core-level
      photoelectron and Auger electron spectra (AES), free from charging effects. The
      AES is interpreted as being intermediate between the molecular and solid water
      spectra showing broadened bands as well as a significant shoulder at high kinetic
      energy. Qualitative considerations as well as ab initio calculations explain this
      shoulder to be due to delocalized final states in which the two valence holes are
      mostly located at different water molecules. The ab initio calculations show that
      valence hole configurations with both valence holes at the core-ionized water
      molecule are admixed to these final states and give rise to their intensity in
      the AES. Density-functional investigations of model systems for the doubly
      ionized final states--the water dimer and a 20-molecule water cluster--were
      performed to analyze the localization of the two valence holes in the electronic
      ground states. Whereas these holes are preferentially located at the same water
      molecule in the dimer, they are delocalized in the cluster showing a preference
      of the holes for surface molecules. The calculated double-ionization potential of
      the cluster (22.1 eV) is in reasonable agreement with the low-energy limit of the
      delocalized hole shoulder in the AES.

PMID- 16108643
TI  - Time-dependent pump-probe spectra of NeBr2.
AB  - Time- and frequency-resolved pump-probe measurements on NeBr2 have been performed
      to better characterize its fragmentation dynamics on the B electronic state for
      vibrational levels in the energy region of the transition from direct vibrational
      predissociation to intramolecular vibrational relaxation dynamics. Above nu'=20
      of the Br2 stretching mode, it was observed that the dependence of lifetime on
      the vibrational quantum number deviates from the energy-gap law by leveling off
      in the range of 10 ps<tau<20 ps. In addition to measuring the appearance of Br2
      product state levels, we were able to monitor the decay of the initially excited
      NeBr2 via B-->E transitions of the complex. These transitions are shifted 20 cm(
      1) to lower energy from the free Br2 resonances, indicating an E state Ne-Br2
      bond energy of 82 cm(-1). Measurements of NeBr2 vibrational predissociation via
      the delta nu=-2 channel were also performed for nu'=27, 28, and 29. The closing
      of the delta nu=-1 channel leads to an increase in the lifetimes of these
      vibrational levels. A new Nd:yttrium aluminum garnet pumped dual optical
      parametric oscillator/optical parametric amplifier system is described that
      allows us to conveniently record time-delayed pump-probe spectra with 2-cm(-1)
      spectral resolution and 15-ps time resolution.

PMID- 16108644
TI  - Dissociation of energy-selected c-C2H4S+ in a region 10.6-11.8 eV: threshold
      photoelectron-photoion coincidence experiments and quantum-chemical calculations.
AB  - Dissociation of energy-selected c-C2H4S+ was investigated in a region of 10.6
      11.8 eV with a threshold photoelectron-photoion coincidence technique and a
      synchrotron as a source of vacuum ultraviolet radiation. Branching ratios and
      average releases of kinetic energy in channels of formation of c-C2H4S+, CH3CS+,
      and HCS+ were obtained from well-resolved time-of-flight peaks in coincidence
      mass spectra. Measured average releases of kinetic energy for channel CH3CS+ + H
      of least energy are substantial and much greater than calculated with
      quasiequilibrium theory; in contrast, small releases of kinetic energy near the
      appearance onset for channel HCS+ + CH3 agree satisfactorily with statistical
      calculations. Calculations of molecular electronic structures and energetics of c
      C2H4S+ and C2H3S+ isomers and various fragments and transition states were also
      performed with Gaussian 3 method to establish dissociation mechanisms. A
      predicted dissociation energy of 11.05 eV for c-C2H4S --> HCS+ + CH3 agrees with
      a linearly extrapolated threshold at 10.99+/-0.04 eV and a predicted dissociation
      mechanism that c-C2H4S+ isomerizes to CH3CHS+ before dissociating to HCS+ + CH3
      supports the experimental results. The large releases of kinetic energy for
      channel CH3CS+ + H might result from a dissociation mechanism according to which
      c-C2H4S+ isomerizes to a local minimum CH3CSH+ and then dissociates through a
      transition state to form CH3CS+ + H.

PMID- 16108645
TI  - Electron-impact ionization of silicon tetrachloride (SiCl4).
AB  - We measured absolute partial cross sections for the formation of various singly
      charged and doubly charged positive ions produced by electron impact on silicon
      tetrachloride (SiCl4) using two different experimental techniques, a time-of
      flight mass spectrometer (TOF-MS) and a fast-neutral-beam apparatus. The energy
      range covered was from the threshold to 900 eV in the TOF-MS and to 200 eV in the
      fast-neutral-beam apparatus. The results obtained by the two different
      experimental techniques were found to agree very well (better than their combined
      margins of error). The SiCl3(+) fragment ion has the largest partial ionization
      cross section with a maximum value of slightly above 6x10(-20) m2 at about 100
      eV. The cross sections for the formation of SiCl4(+), SiCl+, and Cl+ have maximum
      values around 4x10(-20) m2. Some of the cross-section curves exhibit an unusual
      energy dependence with a pronounced low-energy maximum at an energy around 30 eV
      followed by a broad second maximum at around 100 eV. This is similar to what has
      been observed by us earlier for another Cl-containing molecule, TiCl4 [R. Basner,
      M. Schmidt, V. Tamovsky, H. Deutsch, and K. Becker, Thin Solid Films 374 291
      (2000)]. The maximum cross-section values for the formation of the doubly charged
      ions, with the exception of SiCl3(++), are 0.05x10(-20) m2 or less. The
      experimentally determined total single ionization cross section of SiCl4 is
      compared with the results of semiempirical calculations.

PMID- 16108646
TI  - Direct evaluation of the lifetime matrix by the hyperquantization algorithm:
      narrow resonances in the F + H2 reaction dynamics and their splitting for nonzero
      angular momentum.
AB  - We propose a new method for the direct and efficient evaluation of the Felix
      Smith's lifetime Q matrix for reactive scattering problems. Simultaneous
      propagation of the solution to a set of close-coupled equations together with its
      energy derivative allows one to avoid common problems pertinent to the finite
      difference approach. The procedure is implemented on a reactive scattering code
      which employs the hyperquantization algorithm and the Johnson-Manolopoulos [J.
      Comput. Phys. 13, 455 (1973); J. Chem. Phys 85, 6425 (1986)] propagation to
      obtain the complete S matrix and scattering observables. As an application of the
      developed formalism, we focus on the total angular momentum dependence of narrow
      under-barrier resonances supported by van der Waals wells of the title reaction.
      Using our method, we fully characterize these metastable states obtaining their
      positions and lifetimes from Lorentzian fits to the largest eigenvalue of the
      lifetime matrix. Remarkable splittings of the resonances observed at J>0 are
      rationalized in terms of a hyperspherical model. In order to provide an insight
      on the decay mechanism, the Q-matrix eigenvectors are analyzed and the dominant
      channels populated during the decomposition of metastable states are determined.
      Possible relevance of the present results to reactive scattering experiments is
      discussed.

PMID- 16108647
TI  - The all-Cartesian reaction plane Hamiltonian: formulation and application to the
      H-atom transfer in tropolone.
AB  - In this work we present an all-Cartesian reaction surface approach, where the
      large amplitude coordinates span the so-called reaction plane, that is, the
      unique plane defined by the two minima and the saddle-point structure of an
      isomerization reaction. Orthogonal modes are treated within harmonic
      approximation which gives the total Hamiltonian an almost separable form that is
      suitable for multidimensional quantum dynamics calculations. The reaction plane
      Hamiltonian is constructed for the H-atom transfer in tropolone as an example for
      a system with an intramolecular O...H-O hydrogen bond. We find ground-state
      tunneling splittings of 3.5 and 0.16 cm(-1) for the normal and deuterated
      species, respectively. We calculated infrared-absorption spectra for a four
      dimensional model focusing on the low-frequency region. Here, we identify a
      reaction mode which is closely connected to the tautomerization that is reflected
      in the increase of tunneling splitting to 18 cm(-1) upon excitation.

PMID- 16108648
TI  - Dissociative ionization of neon clusters Ne(n), n=3 to 14: a realistic
      multisurface dynamical study.
AB  - The molecular dynamics with quantum transitions (MDQT) method is applied to study
      the fragmentation dynamics of neon clusters following vertical ionization of
      neutral clusters with 3 to 14 atoms. The motion of the neon atoms is treated
      classically, while transitions between the adiabatic electronic states of the
      ionic clusters are treated quantum mechanically. The potential energy surfaces
      are described by the diatomics-in-molecules model in a minimal basis set
      consisting of the effective 2p orbitals on each neon atom for the missing
      electron. The fragmentation mechanism is found to be rather explosive, with a
      large number of events where several atoms simultaneously dissociate. This is in
      contrast with evaporative atom by atom fragmentation. The dynamics are highly
      nonadiabatic, especially at shorter times and for the larger clusters. Initial
      excitation of the neutral clusters does not affect the fragmentation pattern. The
      influence of spin-orbit coupling is also examined and found to be small, except
      for the smaller size systems for which the proportion of the Ne+ fragment is
      increased up to 43%. From the methodological point of view, most of the usual
      momentum adjustment methods at hopping events are shown to induce nonconservation
      of the total nuclear angular momentum because of the nonzero electronic to
      rotation coupling in these systems. A new method for separating out this coupling
      and enforcing the conservation of the total nuclear momentum is proposed. It is
      applied here to the MDQT method of Tully but it is very general and can be
      applied to other surface hopping methods.

PMID- 16108649
TI  - Determination of structural parameters for ferrocenecarboxaldehyde using Fourier
      transform microwave spectroscopy.
AB  - Gas-phase structural parameters for ferrocenecarboxaldehyde have been determined
      using Fourier transform microwave spectroscopy. Rotational transitions due to a-,
      b-, and c-type dipole moments were measured. Eighteen rotational constants were
      determined by fitting the measured transitions of various isotopomers using a
      rigid rotor Hamiltonian with centrifugal distortion constants. Least-squares fit
      and Kraitchman analyses have been used to determine the gas-phase structural
      parameters and the atomic coordinates of the molecule using the rotational
      constants for various isotopomers. Structural parameters determined from the
      least-squares fit are the Fe-C bond lengths to the cyclopentadienyl rings, r(Fe
      C)=2.047(4) A, and the distance between the carbon atoms of the cyclopentadienyl
      rings, r(C-C)=1.430(2) A and r(C1-C1')=1.46(1) A of ring carbon and aldehyde
      carbon atom. Structural parameters were also obtained using density-functional
      theory calculations, and these were quite helpful in resolving ambiguities in the
      structural fit analysis, and providing some fixed parameters for the structural
      analysis. The results of the least squares and the calculations indicate that the
      carbon atoms of the Cp groups for ferrocenecarboxaldehyde are in an eclipsed
      conformation in the ground vibrational state.

PMID- 16108650
TI  - Theoretical characterization of the low-lying electronic states of NbC.
AB  - We have studied the potential-energy curves and the spectroscopic constants of
      the ground and low-lying excited states of NbC by employing the complete active
      space self-consistent field method with relativistic effective core potentials
      followed by multireference configuration-interaction calculations. We have
      identified 23 low-lying electronic states of NbC with different spin
      multiplicities and spatial symmetries within 40,000 cm(-1). At the multireference
      single and double configuration interaction level of theory the 2sigma+ and
      2delta states are nearly degenerated, with the 2delta state located 187 cm(-1)
      lower than the 2sigma+ state. The estimated spin-orbit splitting for the 2delta
      state results in a 2delta(3/2) ground state and A 2sigma+ which is placed 650 cm(
      1) above the ground state, in reasonable agreement with the experimental result,
      831 cm(-1). Our computed spectroscopic constants are in good agreement with
      experimental values although our results differ from those of a previous density
      functional investigation of the excited states of NbC, mainly due to the strong
      multiconfigurational character of NbC. In the present work we have not only
      suggested assignments for the observed states but also computed more electronic
      states that are yet to be observed experimentally.

PMID- 16108651
TI  - Thermal and solvent effects on the NMR and UV parameters of some bioreductive
      drugs.
AB  - 15N NMR chemical shifts and n-->pi* electronic transition energy for
      metronidazole (1) has been calculated and compared with experimental data. A
      detailed computational study of 1 is presented, with special attention to the
      performance of various theoretical methods for reproducing spectroscopic
      parameters in solution. The most sophisticated approach involves density
      functional based on the Car-Parrinello molecular dynamics simulations of 1 in
      aqueous solution (BP86 level) and averaging chemical shifts and deltaE(n-->pi*)
      over snapshots from the trajectory. In the NMR and UV calculations for these
      snapshots (performed at the B3LYP level), a small number of discrete water
      molecules are retained, and the remaining bulk solution effects are included via
      a polarizable continuum model (PCM). A good agreement with experiment is also
      obtained using static geometry optimization and NMR computation of pristine 1
      employing a PCM approach. Further theoretical predictions are also reported for
      17O NMR and deltaE(n-->pi*) of three hydroxycinnamic acid derivatives, which
      suggest that it is essential to incorporate the dynamics and solvent effects for
      NMR and UV calculations in the condensed phase.

PMID- 16108652
TI  - Comparison of rovibronic density of asymmetric versus symmetric NO2 isotopologues
      at dissociation threshold: broken symmetry effects.
AB  - We have measured the rovibronic densities of four symmetric (C2v) and two
      asymmetric (Cs) isotopologues of nitrogen dioxide just below their
      photodissociation threshold. At dissociation threshold and under jet conditions
      the laser-induced fluorescence abruptly disappears because the dissociation into
      NO(2pi(1/2)) + O(3P2) is much faster than the radiative decay. As a consequence,
      in a narrow energy range below D0, the highest bound rovibronic energy levels of
      J=1/2 and J=3/2 can be observed and sorted. A statistical analysis of the
      corresponding rovibronic density, energy spacing, and rovibronic transition
      intensities has been made. The observed intensity distributions are in agreement
      with the Porter-Thomas distribution. This distribution allows one to estimate the
      number of missing levels, and therefore to determine and compare the rovibronic
      and the vibronic densities. The four symmetric NO2 isotopologues, 16O14N16O,
      18O14N18O, 16O15N16O, and 18O15N18O, have, respectively, a sum of J=1/2 and J=3/2
      rovibronic densities of 18+/-0.8, 18.3+/-1.4, 18.4+/-2.7, and 19.8+/-3.5 cm(-1),
      while for the two asymmetric isotopologues, 18O14N16O and 18O15N16O, the
      corresponding densities are 20.9+/-4.5 and 23.6+/-5.6 cm(-1). The corresponding
      vibronic densities are in agreement only if we include both the merging of
      symmetry species (from those of C2v to those of Cs) and the contribution of the
      long-range tail(s) of the potential-energy surface along the dissociation
      coordinate. The effects of isotopic substitution on dissociation rates and the
      possible relation to mass-independent isotopic fractionation are discussed.

PMID- 16108653
TI  - Isomers of GeNO and Ge(NO)2: production and infrared absorption of GeNO and
      ONGeNO in solid Ar.
AB  - Crystalline germanium was ablated with light at 532 nm from a frequency-doubled
      neodymium: yttrium aluminum garnet laser, and the resultant plume reacted with NO
      before deposition onto a substrate at 13 K. Lines in group A at 1543.8 and 3059.7
      cm(-1) that become enhanced at the initial stage of irradiation at 308 or 193 nm
      and also after annealing are attributed to nu1 and 2nu1 of GeNO. Lines in group B
      at 1645.5 and 1482.8 cm(-1) that become diminished after further irradiation of
      the matrix at 308 or 193 nm but become enhanced after annealing are attributed to
      symmetric NO stretch (nu1) and antisymmetric NO stretch (nu7) of ONGeNO. The
      assignments were derived based on wave numbers and isotopic ratios observed in
      the experiments with 15N- and 18O-isotopic substitutions and predicted with
      quantum-chemical calculations. Quantum-chemical calculations with density
      functional theories (B3LYP and BLYP/aug-cc-pVTZ) predict four stable isomers of
      GeNO, six isomers of Ge2NO, and four isomers of Ge(NO)2, with linear GeNO, cyc
      GeNGeO, and cyc-GeONNO having the least energies, respectively. The formation
      mechanisms of GeNO and ONGeNO are discussed. In addition, a weak line at 1417.0
      cm(-1) and two additional lines associated with minor matrix sites at 1423.0 and
      1420.3 cm(-1) are assigned to GeNO-.

PMID- 16108654
TI  - Probing the barrier for CH2CHCO --> CH2CH + CO by the velocity map imaging
      method.
AB  - This work determines the dissociation barrier height for CH2CHCO --> CH2CH + CO
      using two-dimensional product velocity map imaging. The CH2CHCO radical is
      prepared under collision-free conditions from C-Cl bond fission in the
      photodissociation of acryloyl chloride at 235 nm. The nascent CH2CHCO radicals
      that do not dissociate to CH2CH + CO, about 73% of all the radicals produced, are
      detected using 157-nm photoionization. The Cl(2P(3/2)) and Cl(2P(1/2)) atomic
      fragments, momentum matched to both the stable and unstable radicals, are
      detected state selectively by resonance-enhanced multiphoton ionization at 235
      nm. By comparing the total translational energy release distribution P(E(T))
      derived from the measured recoil velocities of the Cl atoms with that derived
      from the momentum-matched radical cophotofragments which do not dissociate, the
      energy threshold at which the CH2CHCO radicals begin to dissociate is determined.
      Based on this energy threshold and conservation of energy, and using calculated C
      Cl bond energies for the precursor to produce CH2CHC*O or C*H2CHCO, respectively,
      we have determined the forward dissociation barriers for the radical to
      dissociate to vinyl + CO. The experimentally determined barrier for CH2CHC*O -->
      CH2CH + CO is 21+/-2 kcal mol(-1), and the computed energy difference between the
      CH2CHC*O and the C*H2CHCO forms of the radical gives the corresponding barrier
      for C*H2CHCO --> CH2CH + CO to be 23+/-2 kcal mol(-1). This experimental
      determination is compared with predictions from electronic structure methods,
      including coupled-cluster, density-functional, and composite Gaussian-3-based
      methods. The comparison shows that density-functional theory predicts too low an
      energy for the C*H2CHCO radical, and thus too high a barrier energy, whereas both
      the Gaussian-3 and the coupled-cluster methods yield predictions in good
      agreement with experiment. The experiment also shows that acryloyl chloride can
      be used as a photolytic precursor at 235 nm of thermodynamically stable CH2CHC*O
      radicals, most with an internal energy distribution ranging from approximately 3
      to approximately 21 kcal mol(-1). We discuss the results with respect to the
      prior work on the O(3P) + propargyl reaction and the analogous O(3P) + allyl
      system.

PMID- 16108655
TI  - Experimental studies of the vapor phase nucleation of refractory compounds. VI.
      The condensation of sodium.
AB  - In this paper we discuss the condensation of sodium vapor and the formation of a
      sodium aerosol as it occurs in a gas evaporation condensation chamber. A one
      dimensional model describing the vapor transport to the vapor/aerosol interface
      was employed to determine the onset supersaturation, in which we assume the
      observed location of the interface is coincident with a nucleation rate maximum.
      We then present and discuss the resulting nucleation onset supersaturation data
      within the context of nucleation theory based on the liquid droplet model.
      Nucleation results appear to be consistent with a cesium vapor-to-liquid
      nucleation study performed in a thermal diffusion cloud chamber.

PMID- 16108656
TI  - Spectroscopy of Ar-SH and Ar-SD. I. Observation of rotation-vibration transitions
      of a van der Waals mode by double-resonance spectroscopy.
AB  - Rotation-vibration transitions of a van der Waals bending vibration, P = 1/2 <--
      3/2, of the Ar-SHSD (X 2pi) complexes in the electronic ground state have been
      observed by applying newly developed microwave-millimeter-wave double-resonance
      spectroscopy. The rotational energy-level structure for the two isotopomers, with
      hyperfine structure due to the hydrogen or deuterium nuclei and parity doublings
      in the P = 1/2 state, has now been clarified. Detailed explanation of the double
      resonance technique is also given.

PMID- 16108657
TI  - Spectroscopy of Ar-SH and Ar-SD. II. Determination of the three-dimensional
      intermolecular potential-energy surface.
AB  - All the pure rotational transitions reported in the previous studies [J. Chem.
      Phys. 113, 10121 (2000); J. Mol. Spectrosc. 222, 22 (2003)] and newly observed
      rotation-vibration transitions, P = 1/2 <-- 3/2, for Ar-SH and Ar-SD [J. Chem.
      Phys. (2005), the preceding paper] have been simultaneously analyzed to determine
      a new intermolecular potential-energy surface of Ar-SH in the ground state. A
      Schrodinger equation considering the three-dimensional freedom of motion for an
      atom-diatom complex in the Jacobi coordinate, R, theta, and r, was numerically
      solved to obtain energies of the rovibrational levels using the discrete variable
      representation method. A three-dimensional potential-energy surface is determined
      by a least-squares fitting with initial values of the parameters for the
      potential obtained by ab initio calculations at the RCCSD(T)/aug-cc-pVTZ level of
      theory. The potential well reproduces all the observed data in the microwave and
      millimeter wave regions with parity doublings and hyperfine splittings. Several
      low-lying rovibrational energies are calculated using the new potential-energy
      surface. The dependence of the interaction energy between Ar and SH(2pi(i)) on
      the bond length of the SH monomer is discussed.

PMID- 16108658
TI  - Rotational spectroscopy and equilibrium structures of S3 and S4.
AB  - The sulfur molecules thiozone S3 and tetrasulfur S4 have been observed in a
      supersonic molecular beam in the centimeter-wave band by Fourier transform
      microwave spectroscopy, and in the millimeter- and submillimeter-wave bands in a
      low-pressure glow discharge. For S3 over 150 rotational transitions between 10
      and 458 GHz were measured, and for S4 a comparable number between 6 and 271 GHz.
      The spectrum of S3 is reproduced to within the measurement uncertainties by an
      asymmetric top Hamiltonian with three rotational and 12 centrifugal distortion
      constants; ten distortion constants, but an additional term to account for very
      small level shifts caused by interchange tunneling, are required to reproduce to
      comparable accuracy the spectrum of S4. Empirical equilibrium (r(e)(emp))
      structures of S3 and S4 were derived from experimental rotational constants of
      the normal and sulfur-34 species and vibrational corrections from coupled-cluster
      theory calculations. Quantum chemical calculations show that interchange
      tunneling occurs because S4 automerizes through a transition state with D2h
      symmetry which lies about 500 cm(-1) above the two equivalent C2upsilon minima on
      the potential energy surface.

PMID- 16108659
TI  - Lifetime of C2Cl4(-) ions produced by nondissociative electron attachment to
      C2Cl4.
AB  - The lifetimes of long-lived C2Cl4(-) ions formed by Rydberg electron transfer in
      K(np)/C2Cl4 collisions are investigated using a Penning ion trap. Measurements at
      high n, n > or = 30, show that low-energy electron attachment to C2Cl4 leads to
      the production of C2Cl4(-) ions with a broad range of lifetimes that extends up
      to at least 1 ms. This is attributed to capture by molecules in different initial
      vibrational states. At low n, internal-to-translational energy transfer in
      postattachment interactions between the product K+ and C2Cl4(-) ions becomes
      important and leads to a substantial increase in ion lifetimes.

PMID- 16108660
TI  - Predicting atomic dopant solvation in helium clusters: the MgHe(n) case.
AB  - We present a quantum Monte Carlo study of the solvation and spectroscopic
      properties of the Mg-doped helium clusters MgHe(n) with n=2-50. Three high-level
      [MP4, CCSD(T), and CCSDT] MgHe interaction potentials have been used to study the
      sensitivity of the dopant location on the shape of the pair interaction. Despite
      the similar MgHe well depth, the pair distribution functions obtained in the
      diffusion Monte Carlo simulations markedly differ for the three pair potentials,
      therefore indicating different solubility properties for Mg in He(n). Moreover,
      we found interesting size effects for the behavior of the Mg impurity. As a
      sensitive probe of the solvation properties, the Mg excitation spectra have been
      simulated for various cluster sizes and compared with the available experimental
      results. The interaction between the excited 1P Mg atom and the He moiety has
      been approximated using the diatomics-in-molecules method and the two excited 1pi
      and 1sigma MgHe potentials. The shape of the simulated MgHe50 spectra shows a
      substantial dependency on the location of the Mg impurity, and hence on the MgHe
      pair interaction employed. To unravel the dependency of the solvation behavior on
      the shape of the computed potentials, exact density-functional theory has been
      adapted to the case of doped He(n) and various energy distributions have been
      computed. The results indicate the shape of the repulsive part of the MgHe
      potential as an important cause of the different behaviors.

PMID- 16108661
TI  - Dynamic molecular interferometer: probe of inversion symmetry in I2(-)
      photodissociation.
AB  - Time-resolved photoelectron imaging of negative ions is employed to examine 780
      nm dissociation dynamics of I2(-), emphasizing the effects of interference in
      time-resolved photoelectron angular distributions obtained with 390-nm probe. No
      energetic changes are observed after about 700 fs, but the evolution of the
      photoelectron anisotropy persists for up to 2.5 ps, indicating that the
      electronic wave function of the dissociating anion continues to evolve long after
      the asymptotic energetic limit of the reaction has been effectively reached. The
      time scale of the anisotropy variation corresponds to a fragment separation of
      the same order of magnitude as the de Broglie wavelength of the emitted electrons
      (lambda=35 A). These findings are interpreted by considering the effect of I2(-)
      inversion symmetry and viewing the dissociating anion as a dynamic molecular
      scale "interferometer," with the electron waves emitted from two separating
      centers. The predictions of the model are in agreement with the present
      experiment and shed new light on previously published results [A. V. Davis, R.
      Wester, A. E. Bragg, and D. M. Neumark, J. Chem. Phys. 118, 999 (2003)].

PMID- 16108662
TI  - Ultraviolet photodissociation dynamics of the SH radical.
AB  - Ultraviolet (UV) photodissociation dynamics of jet-cooled SH radical (in X
      2pi(3/2), nu"=0-2) is studied in the photolysis wavelength region of 216-232 nm
      using high-n Rydberg atom time-of-flight technique. In this wavelength region,
      anisotropy beta parameter of the H-atom product is approximately -1, and spin
      orbit branching fractions of the S(3P(J)) product are close to
      S(3P2):S(3P1):S(3P0)=0.51:0.36:0.13. The UV photolysis of SH is via a direct
      dissociation and is initiated on the repulsive 2sigma- potential-energy curve in
      the Franck-Condon region after the perpendicular transition 2sigma(-)-X 2pi. The
      S(3P(J)) product fine-structure state distribution approaches that in the sudden
      limit dissociation on the single repulsive 2sigma- state, but it is also affected
      by the nonadiabatic couplings among the repulsive 4sigma-, 2sigma-, and 4pi
      states, which redistribute the photodissociation flux from the initially excited
      2sigma- state to the 4sigma- and 4pi states. The bond dissociation energy D0(S
      H)=29,245+/-25 cm(-1) is obtained.

PMID- 16108663
TI  - Perturbational calculations of parity-violating effects in nuclear-magnetic
      resonance parameters.
AB  - We investigate the effects of the parity-violating electroweak interaction in the
      spectral parameters of nuclear magnetic resonance. Perturbational theory of
      parity-violating effects in the nuclear magnetic shielding is presented to the
      order of G(F)alpha, and in the indirect spin-spin coupling, to the order of
      G(F)alpha3. These leading-order parity-violating corrections are evaluated using
      analytical linear-response theory methods based on Hartree-Fock and density
      functional theory reference states. Parity-violating contributions to spin-spin
      couplings are evaluated for the first time at the first-principles level.
      Calculations are carried out for two chiral halomethanes,
      bromochlorofluoromethane and bromofluoroiodomethane.

PMID- 16108664
TI  - Computer simulation of the 13 crystalline phases of ice.
AB  - As a reference for follow-up studies toward more accurate model parametrizations,
      we performed molecular-dynamics and Monte Carlo simulations for all known
      crystalline phases of ice, as described by the simple point-charge/extended and
      TIP4P water models. We started from the measured structures, densities, and
      temperatures, and carried out classical canonical simulations for all these
      arrangements. All simulated samples were cooled down close to 0 K to facilitate
      the comparison with theoretical estimates. We determined configurational internal
      energies as well as pressures, and monitored how accurately the measured
      configurations were preserved during the simulations. While these two models
      predicted very similar thermophysical and structural properties for water at
      ambient conditions, the predicted features for the corresponding ice polymorphs
      may differ significantly.

PMID- 16108665
TI  - The spectra of mixed 3He-4He droplets.
AB  - The diffusion Monte Carlo technique is used to calculate and analyze the
      excitation spectrum of 3He atoms bound to a cluster of 4He atoms by using a
      previously determined optimum filling of single-fermion orbits with well-defined
      orbital angular momentum L, spin S, and parity quantum numbers. The study
      concentrates on the energies and shapes of the three kinds of states for which
      the fermionic part of the wave function is a single Slater determinant: maximum L
      or maximum S states within a given orbit, and fully polarized clusters. The
      picture that emerges is that of systems with strong shell effects, whose binding
      and excitation energies are essentially determined by averages over configuration
      at fixed number of particles and spin, i.e., by the monopole properties of an
      effective Hamiltonian.

PMID- 16108666
TI  - Criterion for the occurrence of the gas-liquid phase transition.
AB  - Using Yang-Lee theory of phase transition and our extension, it is found that for
      a real fluid, both the singularity of canonical partition function and the
      critical point of the gas-liquid phase transition occur precisely at the
      temperature when all the cluster integrals become positive. The critical
      temperature is determined by the limit of the first zeros of the cluster
      integrals.

PMID- 16108667
TI  - A molecular dynamics study of nitric oxide in water: diffusion and structure.
AB  - We present molecular dynamics simulations of the diffusion coefficients and
      structure of water-nitric oxide mixtures at ambient (298 K) and in vivo (310 K)
      conditions. A two-site rigid-body molecular model with partial charges and a
      Lennard-Jones potential on both sites is proposed for nitric oxide and used in
      conjunction with the extended simple point-charge model for liquid water in our
      simulations. The diffusion coefficients obtained from the simulations are in good
      agreement with experimental data. The results from intermolecular partial pair
      functions show that under these thermodynamic conditions, the existence of nitric
      oxide in liquid water has little impact on the structure of water and the
      tendency to form H bonds between water molecules. We also find that it is
      unlikely that H bonds form between the hydrogen atoms in water and either the
      nitrogen or the oxygen atom on the nitric oxide at the temperatures and densities
      examined in this study. This study suggests that in low concentrations nitric
      oxide molecules exist as free molecules in liquid water rather than forming
      complexes with water molecules.

PMID- 16108668
TI  - A potential from quantum chemistry for thermodynamic property predictions for
      methanethiol.
AB  - An ab initio potential for methanethiol is determined by computing quantum
      chemical interaction energies for a range of orientations and center-of-mass
      separation distances. These energies are initially fitted to a pairwise-additive,
      site-site Morse-C6 intermolecular potential. Additional interaction energies were
      then calculated at separation distances determined to be important from the angle
      averaged Mayer f function calculated with the initial potential. This expanded
      set of interaction energies is then fitted using Boltzmann-type weighting to
      obtain the final intermolecular potential. Although there are some discrepancies
      in the fit for a particular type of orientation, the phase behavior calculated
      from Gibbs ensemble Monte Carlo simulations using this final potential is in very
      good agreement with experimental data. The prescription used here for obtaining
      the optimum potential from quantum-chemical methods should be applicable to other
      systems.

PMID- 16108669
TI  - On the caging number of two- and three-dimensional hard spheres.
AB  - Local structural arrest in random packings of colloidal or granular spheres is
      quantified by a caging number, defined as the average minimum number of randomly
      placed spheres on a single sphere that immobilize all its translations. We
      present an analytic solution for the caging number for two-dimensional hard disks
      immobilized by neighbor disks which are placed at random positions under the
      constraint of a nonoverlap condition. Immobilization of a disk with radius r = 1
      by arbitrary larger neighbor disks with radius r > or = 1 is solved analytically,
      whereas for contacting neighbors with radius 0 < r < 1, the caging number can be
      evaluated accurately with an approximate excluded volume model that also applies
      to spheres in higher Euclidean dimension. Comparison of our exact two-dimensional
      caging number with studies on random disk packing indicates that it relates to
      the average coordination number of random loose packing, whereas the parking
      number is more indicative for coordination in random dense packing of disks.

PMID- 16108670
TI  - The importance of vibronic perturbations in ferrocytochrome c spectra: a
      reevaluation of spectral properties based on low-temperature optical absorption,
      resonance Raman, and molecular-dynamics simulations.
AB  - We have measured and analyzed the low-temperature (T=10 K) absorption spectrum of
      reduced horse heart and yeast cytochrome c. Both spectra show split and
      asymmetric Q(0) and Q(upsilon) bands. The spectra were first decomposed into the
      individual split vibronic sidebands assignable to B(1g) (nu15) and A(2g) (nu19,
      nu21, and nu22) Herzberg-Teller active modes due to their strong intensity in
      resonance Raman spectra acquired with Q(0) and Q(upsilon) excitations. The
      measured band splittings and asymmetries cannot be rationalized solely in terms
      of electronic perturbations of the heme macrocycle. On the contrary, they clearly
      point to the importance of considering not only electronic perturbations but
      vibronic perturbations as well. The former are most likely due to the
      heterogeneity of the electric field produced by charged side chains in the
      protein environment, whereas the latter reflect a perturbation potential due to
      multiple heme-protein interactions, which deform the heme structure in the ground
      and excited states. Additional information about vibronic perturbations and the
      associated ground-state deformations are inferred from the depolarization ratios
      of resonance Raman bands. The results of our analysis indicate that the heme
      group in yeast cytochrome c is more nonplanar and more distorted along a B(2g)
      coordinate than in horse heart cytochrome c. This conclusion is supported by
      normal structural decomposition calculations performed on the heme extracted from
      molecular-dynamic simulations of the two investigated proteins. Interestingly,
      the latter are somewhat different from the respective deformations obtained from
      the x-ray structures.

PMID- 16108671
TI  - Time-resolved optical Kerr-effect investigation on CS2/polystyrene mixtures.
AB  - The relaxation dynamics of carbon disulfide are investigated in mixtures with
      polystyrene (PS) using the time-resolved optical heterodyne-detected optical Kerr
      effect (OHD-OKE). The data are analyzed using both the model-dependent approach,
      which assumes four distinct temporal responses, and the model-independent Fourier
      transform approach, which generates a spectral response that can be compared with
      results obtained by depolarized Rayleigh scattering. A slow dynamics is observed
      for the OHD-OKE transient decaying exponentially with a time constant that varies
      from 1.68 ps for neat CS2 to 3.76 ps for the most concentrated CS2PS mixture. The
      increase of this time constant accompanies an increase in the viscosity of the
      mixture, so we can associate this component with the diffusive reorientation
      process of the induced polarizability anisotropy of the carbon disulfide in the
      mixture. The short-time nuclear response is characterized in the frequency domain
      by a broad band that peaks around 30 cm(-1) for neat carbon disulfide, and is
      associated with a complex relaxation pattern. The vibrational distribution shifts
      to higher frequencies when the PS concentration is increased in the mixture. This
      result is discussed in terms of an increase in the interaction strength between
      the PS phenyl rings and the carbon disulfide molecules.

PMID- 16108672
TI  - The Kohn-Sham density of states and band gap of water: from small clusters to
      liquid water.
AB  - Electronic properties of water clusters (H2O)(n), with n=2, 4, 8, 10, 15, 20, and
      30 molecules were investigated by sequential Monte Carlo/density-functional
      theory (DFT) calculations. DFT calculations were carried out over uncorrelated
      configurations generated by Monte Carlo simulations of liquid water with a
      reparametrized exchange-correlation functional that reproduces the experimental
      information on the electronic properties (first ionization energy and highest
      occupied molecular orbital-lowest unoccupied molecular orbital gap) of the water
      dimer. The dependence of electronic properties on the cluster size (n) shows that
      the density of states (DOS) of small water clusters (n>10) exhibits the same
      basic features that are typical of larger aggregates, such as the mixing of the
      3a1 and 1b1 valence bands. When long-ranged polarization effects are taken into
      account by the introduction of embedding charges, the DOS associated with 3a1
      orbitals is significantly enhanced. In agreement with valence-band photoelectron
      spectra of liquid water, the 1b1, 3a1, and 1b2 electron binding energies in water
      aggregates are redshifted by approximately 1 eV relative to the isolated
      molecule. By extrapolating the results for larger clusters the threshold energy
      for photoelectron emission is 9.6+/-0.15 eV (free clusters) and 10.58+/-0.10 eV
      (embedded clusters). Our results for the electron affinity (V0=-0.17+/-0.05 eV)
      and adiabatic band gap (E(G,Ad)=6.83+/-0.05 eV) of liquid water are in excellent
      agreement with recent information from theoretical and experimental works.

PMID- 16108673
TI  - Structure of hard-sphere fluid and precursor structures to crystallization.
AB  - The structural origin of the commonly observed split second peak of the radial
      distribution function of a supercooled or glassy liquid is examined in this work
      using the hard-sphere fluid as an example. A novel approach to the analysis of
      the microscopic structure of a fluid is described, which permits the
      decomposition of both the radial distribution function and bond-angle
      distribution function of a system of particles into contributions from a small
      number of ring structures. The method uses a modified shortest-path definition of
      rings appropriate to the analysis of the medium-range structure of dense systems.
      It is shown that the split peak is an indicator of the emergence of precursor
      structures to crystal formation. The origin of the split peak provides a
      structural link between fluid and crystalline phases and our results suggest that
      it is neither a structural feature peculiar to glassy phases nor a smooth
      structural continuation of the stable-fluid phase. This structural feature of
      simple glassy systems is more appropriately described as a signifier of the
      frustration of emerging crystalline order in a fluid.

PMID- 16108674
TI  - Vibrational energy relaxation of azulene studied by the transient grating method.
      I. Supercritical fluids.
AB  - The vibrational energy dissipation process of the ground-state azulene in
      supercritical xenon, carbon dioxide, and ethane has been studied by the transient
      grating spectroscopy. In this method, azulene in these fluids was photoexcited by
      two counterpropagating subpicosecond laser pulses at 570 nm, which created a
      sinusoidal pattern of vibrationally hot ground-state azulene inside the fluids.
      The photoacoustic signal produced by the temperature rise of the solvent due to
      the vibrational energy relaxation of azulene was monitored by the diffraction of
      a probe pulse. The temperature-rise time constants of the solvents were
      determined at 383 and 298 K from 0.7 to 2.4 in rho(r), where rho(r) is the
      reduced density by the critical density of the fluids, by the fitting of the
      acoustic signal based on a theoretical model equation. In xenon, the temperature
      rise time constant was almost similar to the vibrational energy-relaxation time
      constant of the photoexcited solute determined by the transient absorption
      measurement [D. Schwarzer, J. Troe, M. Votsmeier, and M. Zerezke, J. Chem. Phys.
      105, 3121 (1996)] at the same reduced density irrespective of the solvent
      temperature. On the other hand, the temperature-rise time constants in ethane
      were larger than the vibrational energy-relaxation time constants by a factor of
      about 2. In carbon dioxide, the difference was small. From these results, the
      larger time constants of the solvent temperature rise than those of the
      vibrational energy relaxation in ethane and carbon dioxide were interpreted in
      terms of the vibrational-vibrational (V-V) energy transfer between azulene and
      solvent molecules and the vibrational-translational (V-T) energy transfer between
      solvent molecules. The contribution of the V-V energy transfer process against
      the V-T energy transfer process has been discussed.

PMID- 16108675
TI  - Vibrational energy relaxation of azulene studied by the transient grating method.
      II. Liquid solvents.
AB  - The vibrational energy dissipation process of the ground-state azulene in various
      liquids has been studied by the transient grating spectroscopy. The acoustic
      signal produced by the temperature rise of the solvent due to the vibrational
      energy relaxation of azulene was monitored. The temperature rise-time constant of
      the solvent has been determined both by the fitting of the acoustic signal to a
      theoretical model equation and by the analysis of the acoustic peak shift. We
      found that the temperature rise-time constants determined by the transient
      grating method in various solvents are larger than the vibrational energy
      relaxation time constants determined by the transient absorption measurement [D.
      Schwarzer, J. Troe, M. Votsmeier, and M. Zerezke, J. Chem. Phys. 105, 3121
      (1996)]. The difference is explained by different energy dissipation pathways
      from azulene to solvent; vibrational-vibrational (V-V) energy transfer and
      vibrational-translational (V-T) energy transfer. The contribution of the V-V
      energy transfer is estimated in various liquid solvents from the difference
      between the temperature rise time and vibrational energy relaxation time, and the
      solvent V-T relaxation time.

PMID- 16108676
TI  - An extended ab initio QM/MM MD approach to structure and dynamics of Zn(II) in
      aqueous solution.
AB  - Structural and dynamical properties of Zn(II) in aqueous solution were
      investigated, based on an ab initio quantum mechanical/molecular mechanical
      (QM/MM) molecular dynamics simulation at double-zeta Hartree-Fock quantum
      mechanical level including the first and second hydration shells into the QM
      region. The inclusion of the second shell in the QM region resulted in
      significant changes in the properties of the hydrate. The first shell
      coordination number was found to be 6, the second shell consists of approximately
      14 water molecules. The structural properties were determined in terms of RDF,
      ADF, tilt and theta angle distributions, while dynamics were characterized by
      mean ligand residence times, ion-ligand stretching frequencies and the
      vibrational and librational motions of water ligands.

PMID- 16108677
TI  - Probing correlated spectral motion: two-color photon echo study of Nile blue.
AB  - We performed two-color three-pulse photon echo peak shift experiments on Nile
      blue in ethylene glycol and acetonitrile to determine the role of solvent
      dynamics in correlated spectral motion. The system was pumped near the absorption
      maximum and the correlation between the initial state and the final state was
      probed at a number of wavelengths, from the absorption maximum to the
      fluorescence maximum. In addition to solvent dynamics, we found that strongly
      coupled intramolecular vibrations generated correlations between different
      spectral regions. The inertial solvent response was found for both solvents to
      have a time scale on the order of 100-145 fs. This response contributed half of
      the solvent interaction strength for acetonitrile, but less than a third for
      ethylene glycol. Several diffusive time scales were observed: 500 fs and 2.5 ps
      for acetonitrile, and 1, 15, and 100 ps for ethylene glycol. A single description
      of the solvation dynamics was insufficient to quantitatively describe the
      dynamics at all probe wavelengths, which could indicate different dynamics in the
      ground and excited states or the presence of an additional contribution to the
      signal from the excited-state absorption.

PMID- 16108678
TI  - Identification of dielectric and structural relaxations in glass-forming
      secondary amides.
AB  - Dielectric relaxation dynamics of secondary amides is explored in their
      supercooled state near the glass transition temperature Tg by investigating N
      ethylacetamide and its mixtures with N-methylformamide. All the samples are found
      to exhibit giant dielectric permittivities, reaching over 500 in N
      methylformamide-rich mixtures around Tg. For both the neat and binary systems,
      the predominant relaxation peak is of the Debye-type throughout the viscous
      regime, which is an unexpected feature for a glass former with intermediate
      fragility. The present results combined with the earlier reported high
      temperature data reveal that the dielectric strength delta epsilon(D) of the
      Debye relaxation extrapolates to zero at frequencies of 10(10)-10(11) Hz, which
      is about two orders of magnitude lower than the phonon frequency limit typical of
      the structural relaxation. This Debye process is remarkably similar to the
      dielectric behavior of many monohydroxy alcohols, which implies a common nature
      of purely exponential relaxation dynamics in these liquids. Based on the
      dielectric properties, we conclude that the Debye relaxation in the secondary
      amides is not a direct signature of the primary or alpha-relaxation, the latter
      being obscured at low temperatures due to the relatively low permittivity and
      close spectral proximity to the Debye peak. As in the case of monohydroxy
      alcohols, dielectric polarization and structure fluctuate on different time
      scales in secondary amides. The Kirkwood-Frohlich correlation factors for Debye
      type liquids are also discussed.

PMID- 16108679
TI  - Transient and steady state CO oxidation kinetics on nanolithographically prepared
      supported Pd model catalysts: experiments and simulations.
AB  - Applying molecular-beam methods to a nanolithographically prepared planar PdSiO2
      model catalyst, we have performed a detailed study of the kinetics of CO
      oxidation. The model catalyst was prepared by electron-beam lithography, allowing
      individual control of particle size and position. The sample was structurally
      characterized by atomic force microscopy and scanning electron microscopy before
      and after reaction. In the kinetic experiments, the O-rich and CO-rich regimes
      were investigated systematically with respect to their transient and steady-state
      behaviors, both under bistable and monostable reaction conditions. Separate
      molecular beams were used in order to supply the reactants, allowing individual
      control over the reactant fluxes. The desorbing CO2 was detected by both angle
      resolved and angle-integrated mass spectrometries. The experimental results were
      analyzed using different types of microkinetic models, including a detailed
      reaction-diffusion model, which takes into account the structural parameters of
      the catalyst as well as scattering of the reactants from the support. The model
      quantitatively reproduces the results as a function of the reactant fluxes and
      the surface temperature. Various kinetic effects observed are discussed in detail
      on the basis of the model. Specifically, it is shown that under conditions of
      limited oxygen mobility, the switching behavior between the kinetic regimes is
      largely driven by the surface mobility of CO.

PMID- 16108680
TI  - Electron-stimulated sputtering of thin amorphous solid water films on Pt(111).
AB  - The electron-stimulated sputtering of thin amorphous solid water films deposited
      on Pt(111) is investigated. The sputtering appears to be dominated by two
      processes: (1) electron-stimulated desorption of water molecules and (2) electron
      stimulated reactions leading to the production of molecular hydrogen and
      molecular oxygen. The electron-stimulated desorption of water increases
      monotonically with increasing film thickness. In contrast, the total sputtering-
      which includes all electron-stimulated reaction channels--is maximized for films
      of intermediate thickness. The sputtering yield versus thickness indicates that
      erosion of the film occurs due to reactions at both the water/vacuum interface
      and the Pt/water interface. Experiments with layered films of D2O and H2O
      demonstrate significant loss of hydrogen due to reactions at the Pt/water
      interface. The electron-stimulated sputtering is independent of temperature below
      approximately 80 K and increases rapidly at higher temperatures.

PMID- 16108681
TI  - Behavior of mixtures of symmetric and asymmetric electrolytes near discretely
      charged planar surfaces: a Monte Carlo study.
AB  - Canonical Monte Carlo (CMC) simulations are employed in this work in order to
      study the structure of the electrical double layer (EDL) near discretely charged
      planar surfaces in the presence of symmetric and asymmetric indifferent
      electrolytes within the framework of a primitive model. The effects of
      discreteness and strength of surface charge, charge asymmetry, and size asymmetry
      are specific focuses of this work. The CMC simulation protocol is initially
      tested against the classical theory, the modified Gouy-Chapman (GC) theory, in
      order to assess the reliability of the simulation results. The CMC simulation
      results and the predictions of the classical theory show good agreement for 1:1
      electrolytes and low surface charge, at which conditions the GC theory is valid.
      Simulations with symmetric and asymmetric electrolytes and mixtures of the two
      demonstrate that size plays an important role in determining the species present
      in the EDL and how the surface charge is screened. A size-exclusion effect could
      be consistently detected. Although it is energetically favorable that higher
      valence ions screen the surface charge, their larger size prevents them from
      getting close to the surface. Smaller ions with lower valences perform the
      screening of the charge, resulting in higher local concentrations of small ions
      close to the surface. The simulations also showed that the strength of the
      surface charge enhances the size-exclusion effect. This effect will definitely
      affect the magnitude of the forces between interacting charged surfaces.

PMID- 16108682
TI  - Mechanisms of fluorescence blinking in semiconductor nanocrystal quantum dots.
AB  - The light-induced spectral diffusion and fluorescence intermittency (blinking) of
      semiconductor nanocrystal quantum dots are investigated theoretically using a
      diffusion-controlled electron-transfer (DCET) model, where a light-induced one
      dimensional diffusion process in energy space is considered. Unlike the
      conventional electron-transfer reactions with simple exponential kinetics, the
      model naturally leads to a power-law statistics for the intermittency. We
      formulate a possible explanation for the spectral broadening and its
      proportionality to the light energy density, the -32 power law for the blinking
      statistics of the fluorescence intermittency, the breakdown of the power-law
      behavior with a bending tail for the "light" periods, a lack of bending tail for
      the "dark" periods (but would eventually appear at later times), and the
      dependence of the bending tail on light intensity and temperature. This DCET
      model predicts a critical time t(c) (a function of the electronic coupling
      strength and other quantities), such that for times shorter than t(c) the
      exponent for the power law is -12 instead of -32. Quantitative analyses are made
      of the experimental data on spectral diffusion and on the asymmetric blinking
      statistics for the "on" and "off" events. Causes for deviation of the exponent
      from the ideal value of -32 are also discussed. Several fundamental properties
      are determined from the present experimental data, the diffusion correlation
      time, the Stokes shift, and a combination of other molecular-based quantities.
      Specific experiments are suggested to test the model further, extract other
      molecular properties, and elucidate more details of the light-induced charge
      transfer dynamics in quantum dots.

PMID- 16108683
TI  - Pressure-induced hexagonal phase in a ternary microemulsion system composed of a
      nonionic surfactant, water, and oil.
AB  - The pressure-induced phase transition in a microemulsion, consisting of
      pentaethylene glycol mono-n-dodecyl ether, water, and n-octane, was investigated
      by means of small-angle neutron scattering. A pressure-induced phase transition
      from a lamellar structure to a hexagonal structure was observed. The temperature
      pressure phase boundary shows a positive slope with dTdP approximately 0.09 KMPa.
      The structure unit of the high-pressure hexagonal phase was an oil-in-water
      cylinder with the membrane thickness of 15.5 A, identical to the low-temperature
      hexagonal phase. Pressurizing was found to have the same effect by decreasing
      temperature. This behavior was satisfactorily explained with the pressure
      dependence of the spontaneous curvature of surfactant membranes. That is, the
      volume change of surfactant tails plays a dominant role in the structure change
      of the microemulsion with applying pressure.

PMID- 16108684
TI  - Molecular self-diffusion in nanoscale cylindrical pores and classical Fick's law
      predictions.
AB  - Molecular-dynamics calculations are carried out to study the self-diffusion of
      water molecules confined in cylindrical pores. It is found that the classical
      Fick's law description provides a surprisingly accurate prediction for the
      general behaviors of self-diffusion even for pore size of a few molecular
      diameters. The diffusion coefficient in the axial direction is reduced relative
      to bulk fluids for pore size less than about ten molecular diameters. In the
      radial direction, the mean-square displacement accurately follows Fick's law
      prediction, but with an average diffusion coefficient slightly lower than the
      bulk value. The origin of the diffusion behaviors is traced to the molecular
      motion in the restricted geometry of the cylindrical pores.

PMID- 16108685
TI  - Structure of water nanoconfined between hydrophobic surfaces.
AB  - We report the results of a series of molecular-dynamics simulations of liquid
      water confined between two graphite plates with separations ranging from 7 to 15
      A. Energies and free energies are provided, indicating also the corresponding
      stability density span of confined water phases. The structure of the different
      liquid layers is also discussed for all the considered systems. In particular, we
      studied atomic density profiles, two-dimensional radial distribution functions,
      hydrogen bonding, and angular orientations near the carbon plates.

PMID- 16108686
TI  - Diffusion and microstructural properties of solutions of charged nanosized
      proteins: experiment versus theory.
AB  - We have reanalyzed our former static small-angle x-ray scattering and photon
      correlation spectroscopy results on dense solutions of charged spherical
      apoferritin proteins using theories recently developed for studies of colloids.
      The static structure factors S(q), and the small-wave-number collective diffusion
      coefficient D(c) determined from those experiments are interpreted now in terms
      of a theoretical scheme based on a Derjaguin-Landau-Verwey-Overbeek-type
      continuum model of charged colloidal spheres. This scheme accounts, in an
      approximate way, for many-body hydrodynamic interactions. Stokesian dynamics
      computer simulations of the hydrodynamic function have been performed for the
      first time for dense charge-stabilized dispersions to assess the accuracy of the
      theoretical scheme. We show that the continuum model allows for a consistent
      description of all experimental results, and that the effective particle charge
      is dependent upon the protein concentration relative to the added salt
      concentration. In addition, we discuss the consequences of small ions dynamics
      for the collective protein diffusion within the framework of the coupled-mode
      theory.

PMID- 16108687
TI  - Self-organization in protein folding and the hydrophobic interaction.
AB  - Self-organization is a critical aspect of living systems. During the folding of
      protein molecules, the hydrophobic interaction plays an important role in the
      collapse of the peptide chain to a compact shape. As the hydrophobic core
      tightens and excludes water, not only does the number of hydrophobic side chain
      contacts increase, but stabilization is further enhanced by an increase in
      strength of each hydrophobic interaction between side chains in the core. Thus,
      the self-organization of the protein folding process augments itself by enhancing
      the stability of the core against large-scale motions that would unfold the
      protein. Through calculations and computer simulations on a model four-helix
      bundle protein, we show how the strengthening of the hydrophobic interaction is
      crucial for stabilizing the core long enough for completion of the folding
      process and quantitatively manifests self-organizing dynamical behavior.

PMID- 16108688
TI  - Computer simulation of polymer networks: swelling by binary Lennard-Jones
      mixtures.
AB  - The swelling of regular, tightly meshed model networks is investigated by a
      molecular-dynamics-Monte Carlo hybrid technique. The chemical equilibrium between
      two simulation boxes representing the gel phase and a solvent bath, respectively,
      is obtained by subjecting the Lennard-Jones particles of a binary mixture,
      serving as explicit solvent, to the particle transfer step of Gibbs ensemble
      Monte Carlo. The swelling behavior, especially preferential absorption of a
      single component, whose dependence on temperature, pressure, and fluid
      composition is studied, also depends significantly on the size of the central
      simulation cell. These finite-size effects correlate well with those exhibited by
      the density of solvent-free (dry) networks. A theoretical expression, whose
      derivation is based on network elasticity (of dry networks) yields finite-size
      scaling behavior in good accord with simulation results for both dry networks and
      gels in contact with solvent baths. This expression can be used to extrapolate
      the swelling behavior of simulated finite systems to infinite system size.

PMID- 16108689
TI  - Studies on the behavior of nanoconfined homopolymers with cyclic chain
      architecture.
AB  - We have performed Monte Carlo simulations to study the effect of cyclic
      architecture on the behavior of homopolymer chains under several conditions of
      confinement. The collapse of the rings in two stages, a coil-to-globule and a
      liquidlike-to-solidlike transition, was observed even at extreme confinement.
      Both transitions were observed at lower temperatures than for linear chains of
      the same length, 2%-5% lower for unconfined systems, and 10%-15% lower for wall
      separations below three bond lengths due to the effect of confinement. When the
      plates separation approached the two-dimensional regime, the coil-to-globule
      transition shifted to lower temperatures. The inverse trend was observed when the
      chain length was increased. In the collapsed state, the average size and
      conformations of linear and cyclic molecules of same length were similar
      independently of confinement. At temperatures near the coil-to-globule
      transition, the radius of gyration of unconfined linear chains,
      [R(g)(2)](linear), became larger than for the cyclic chains, [R(g)(2)](cyclic),
      and this difference increased considerably with confinement. The radius of
      gyration ratio [R(g)(2)](linear)/[R(g)(2)](cyclic) in this region decreased
      rapidly. The decrease was more pronounced and occurred at lower temperatures for
      slit width confinements. At higher temperatures, in the coil state, the radius of
      gyration ratio became nearly constant for a given separation, and varied from
      0.56 for unconfined systems to 0.47 when the chain was completely confined
      between the walls. This reduction was attributed to the higher increase in the
      average size of linear chains with confinement when compared with cyclic chains,
      due to architectural restrictions.

PMID- 16108690
TI  - Design of amino acid sequences to fold into C(alpha)-model proteins.
AB  - In order to extend the results obtained with minimal lattice models to more
      realistic systems, we study a model where proteins are described as a chain of 20
      kinds of structureless amino acids moving in a continuum space and interacting
      through a contact potential controlled by a 20x20 quenched random matrix. The
      goal of the present work is to design and characterize amino acid sequences
      folding to the SH3 conformation, a 60-residue recognition domain common to many
      regulatory proteins. We show that a number of sequences can fold, starting from a
      random conformation, to within a distance root-mean-square deviation between 2.6
      and 4.0 A from the native state. Good folders are those sequences displaying in
      the native conformation an energy lower than a sequence-independent threshold
      energy.

PMID- 16108691
TI  - Ionic correlations in highly charge-asymmetric colloidal liquids.
AB  - We use electrophoretic mobility (mu) measurements of charged colloidal particles
      under the presence of multivalent counterions as a probe of the electrostatic
      correlations between them; they become important for sufficiently high surface
      charge densities of the colloid (sigma) and result in a decreasing mu upon
      increasing sigma. The physics of this decrease is the same as that giving rise to
      charge inversion. We account qualitatively for the observations by considering
      recent theoretical arguments that assume the counterions next to the colloid
      surface as a strongly correlated liquid of properties similar to that of a Wigner
      crystal.

PMID- 16108692
TI  - Miscibility of small colloidal spheres with large polymers in good solvent.
AB  - Nearly athermal colloid-polymer mixtures were studied in the "protein limit." A
      fluid-fluid transition was observed in mixtures of stearyl-alcohol-coated silica
      particles and large polystyrene coils in toluene. The ratios of the polymer
      radius of gyration to the particle radii were q=4.1 and q=5.2. The binodal curves
      and the critical points were determined. Turbidity measurements and analysis for
      one set of particles allowed the systems to be mapped onto hard sphere-polymer
      mixtures. A comparison with recent predictions for the miscibility of model
      mixtures shows that the experimental binodals lie between the two extreme results
      for ideal and interacting polymers. The critical colloid volume fraction is also
      found to decrease with increasing size ratios.

PMID- 16108693
TI  - Nonequilibrium molecular dynamics of the rheological and structural properties of
      linear and branched molecules. Simple shear and poiseuille flows; instabilities
      and slip.
AB  - Nonequilibrium molecular-dynamics simulations are performed for linear and
      branched chain molecules to study their rheological and structural properties
      under simple shear and Poiseuille flows. Molecules are described by a spring
      monomer model with a given intermolecular potential. The equations of motion are
      solved for shear and Poiseuille flows with Lees and Edward's [A. W. Lees and S.
      F. Edwards, J. Phys. C 5, 1921 (1972)] periodic boundary conditions. A multiple
      time-scale algorithm extended to nonequilibrium situations is used as the
      integration method, and the simulations are performed at constant temperature
      using Nose-Hoover [S. Nose, J. Chem. Phys. 81, 511 (1984)] dynamics. In simple
      shear, molecules with flow-induced ellipsoidal shape, having significant segment
      concentrations along the gradient and neutral directions, exhibit substantial
      flow resistance. Linear molecules have larger zero-shear-rate viscosity than that
      of branched molecules, however, this behavior reverses as the shear rate is
      increased. The relaxation time of the molecules is associated with segment
      concentrations directed along the gradient and neutral directions, and hence it
      depends on structure and molecular weight. The results of this study are in
      qualitative agreement with other simulation studies and with experimental data.
      The pressure (Poiseuille) flow is induced by an external force F(e) simulated by
      confining the molecules in the region between surfaces which have attractive
      forces. Conditions at the boundary strongly influence the type of the slip flow
      predicted. A parabolic velocity profile with apparent slip on the wall is
      predicted under weakly attractive wall conditions, independent of molecular
      structure. In the case of strongly attractive walls, a layer of adhered molecules
      to the wall produces an abrupt distortion of the velocity profile which leads to
      slip between fluid layers with magnitude that depends on the molecular structure.
      Finally, the molecular deformation under flow depends on the attractive force of
      the wall, in such a way that molecules are highly deformed in the case of strong
      attracting walls.

PMID- 16108694
TI  - Simulations of concentrated suspensions of rigid fibers: relationship between
      short-time diffusivities and the long-time rotational diffusion.
AB  - Brownian dynamics simulations of the behavior of suspensions of fibers
      demonstrate that the scaling of the rotational diffusivity with respect to the
      number density (nL3) is a sensitive function of the thickness and the parameter
      L2D(R0)/D(T0), where D(R0) is the rotational diffusivity at infinite dilution,
      D(T0) is the average center-of-mass diffusivity at infinite dilution, and L is
      the fiber length. Existing theories for the long-time rotational diffusivities of
      rigid fibers in the semidilute and concentrated regimes fail to accurately
      account for the relationship with the dilute values of the rotational and
      translational diffusivities of the various physical models used to simulate the
      fibers. The concentration regime studied in this work ranges from a number
      density of nL3 approximately 0-150, which is below the transition from an
      isotropic to nematic state. The effect of the fiber thickness was studied by
      performing simulations of rods with aspect ratios (fiber length over diameter) of
      25, 50, and 500, as well as performing projections for infinitely thin fibers.
      The excluded volume of the rods was enforced through the use of short-range
      potentials. For a rod with an aspect ratio of 50 with a parameter of
      L2D(R0)/D(T0)=9, which corresponds to a slender-body model of the individual
      fibers, the rotational diffusivity (D(R)) scales as D(R)/D(R0) approximately
      (nL3)(-1.9) in the concentration regime of 70 < or = nL3 < or = 150. Similarly
      with a parameter of L2D(R0)/D(T0)=4, corresponding to a rigid-dumbbell model, the
      rotational diffusivity scales as D(R)/D(R0) approximately (nL3)(-1.1) over the
      same range of concentrations. For rods with aspect ratios of 25, it is observed
      that a difference in the scaling is seen for L2D(R0)/D(T0) approximately < 8,
      with higher values of this ratio exhibiting essentially the same scaling.
      Additional values of the ratio L2D(R0)/D(T0) were investigated to determine the
      overall behavior of the suspension dynamics with respect to this parameter. These
      findings resolve discrepancies between simulation results for rotational
      diffusivities reported by previous investigators and provide new insights for the
      development of an accurate theory for the diffusivity of rigid rods suspended in
      solution.

PMID- 16108696
TI  - Hexagonal close-packing structure on a cubic cell.

PMID- 16108700
TI  - Why not the best? How science failed the Florida panther.

PMID- 16108695
TI  - A protein molecule in an aqueous mixed solvent: fluctuation theory outlook.
AB  - In the present paper a procedure to calculate the properties of proteins in
      aqueous mixed solvents, particularly the excesses of the constituents of the
      mixed solvent near the protein molecule and the preferential binding parameters,
      is suggested. Expressions for the Kirkwood-Buff integrals in ternary mixtures and
      for the preferential binding parameter were derived and used to calculate various
      properties of infinitely dilute proteins in aqueous mixed solvents. The derived
      expressions and experimental information regarding the partial molar volumes and
      the preferential binding parameters were used to calculate the excesses
      (deficits) of water and cosolvent (in comparison with the bulk concentrations of
      protein-free mixed solvent) in the vicinity of ribonuclease A, ribonuclease T1,
      and lysozyme molecules. The calculations showed that water was in excess in the
      vicinity of ribonuclease A for water/glycerol and water/trehalose mixtures, and
      the cosolvent urea was in excess in the vicinity of ribonuclease T1 and lysozyme.
      The derivative of the activity coefficient of the protein with respect to the
      mole fraction of water was also calculated. This derivative was negative for the
      water/glycerol and water/trehalose mixed solvents and positive for the water/urea
      mixture. The mixture of lysozyme in the water/urea solvent is of particular
      interest, because the lysozyme at pH 7.0 is in its native state up to 9.3M urea,
      while at pH 2.0 it is denaturated between 2.5 and 5M and higher concentrations of
      urea. Our results demonstrated a striking similarity in the hydration of lysozyme
      at both pHs. It is worthwhile to note that the excesses of urea were only weakly
      composition dependent on both cases.

PMID- 16108701
TI  - Measuring the frequency of functional gastrointestinal disorders in rural Crete:
      a need for improving primary care physicians' diagnostic skills.
AB  - INTRODUCTION: Studies of the frequency and aetiology of functional
      gastrointestinal disorders in the general population have received increasing
      interest over the past few years; the field seems to be neglected in Southern
      Europe. The aim of this study was to report on the frequency of functional
      dyspepsia (FD), irritable bowel syndrome (IBS) and gastroenteritis within the
      primary care setting, to provide some information on the extent to which the
      recorded diagnoses in the physicians' notes fulfil existing diagnostic criteria.
      METHOD: A retrospective study was used, where all new cases of these diseases at
      five primary health care centres in three rural and two semi-rural areas of Crete
      were identified by scrutinizing medical records from 280,000 consecutive visits
      during a 4 year period. The occurrence rate per 1000 person-years were calculated
      for the three conditions. We also checked the extent to which the Talley's
      criteria for FD and Rome II diagnostic criteria for IBS were followed. RESULTS:
      Gastroenteritis was revealed to be a quite frequent health problem among the
      rural population on Crete, while the occurrence rates for other problems, such as
      dyspepsia and IBS, were found to be lower than expected. IBS was over-represented
      among women compared with men, OR 2.04 (CI 1.39-3.00). In many cases a diagnosis
      of FD, IBS or gastroenteritis was evident to the research team on the basis of
      findings recorded in the notes, but the diagnosis was not recorded by the
      clinician at the time of consultation. CONCLUSIONS: This study yielded two key
      messages: the first that gastroenteritis is still a frequent health problem, and
      the second that primary care physicians in rural Crete seem to fail in adequately
      diagnosing FD and IBS and need further training.

PMID- 16108702
TI  - Development of 'rural week' for medical students: impact and quality report.
AB  - INTRODUCTION: The Rural Undergraduate Support and Coordination program funds
      medical schools to provide all medical students some time in rural Australia
      throughout their course. The University of Adelaide has developed a rural week
      program for both first and second year students to fulfill part of this
      objective. METHODS: First year students' rural week is an introduction to a range
      of rural health issues, Indigenous culture and rural lifestyle issues. Second
      year students choose either a clinical rural week with a general practitioner or
      a week of Indigenous cultural learning with the Adnyamathanha people in the
      Flinders ranges, South Australia. Evaluation data were collected from students,
      practitioners and university staff during rural weeks in 2003 and 2004 using
      quantitative and qualitative methods. RESULTS: First year students increased
      their knowledge of and interest in rural medicine and enjoyed their (limited)
      clinical interaction with patients. Second year students appreciated the clinical
      experience and valued the welcome they received from doctors and practice staff.
      Those who chose Indigenous cultural programs appreciated the opportunity to
      interact with and learn from Indigenous people. General practitioners valued
      contributing to student knowledge and skills and the opportunity to promote rural
      practice. Volunteer community members were very enthusiastic about meeting the
      students and their generosity had a significant impact on the students' ideas
      about rural lifestyle. University academic and administrative staff found rural
      week very intensive work but experience and thorough preparation now ensures that
      few problems occur. CONCLUSION: Rural weeks are now an established part of the
      first year and second year curriculum at the University of Adelaide Medical
      School. The ability to provide small groups of students with an intense
      introduction to rural practice and/or Indigenous culture results in a positive
      change in opinion about this aspect of medical education. Students now have first
      hand experience to positively influence their choice of rural education or
      Indigenous health options in the medical course. Problems do occur with students
      being away from the traditional classroom, and protocols have been put in place
      for behaviour of all parties. Despite the rural weeks program being very
      demanding on staff energy, financial resources, general practices and rural
      communities, we feel that this program is valuable and sustainable. Further
      experience will determine if rural weeks function effectively as a recruitment
      strategy for the long rural placements offered by the Rural Clinical School.

PMID- 16108703
TI  - Special RECOMB 2004 Issue. Papers presented at the 8th Annual International
      Conference on Computational Biology, San Diego, California, USA, March 27-31,
      2004.

PMID- 16108704
TI  - A random graph approach to NMR sequential assignment.
AB  - Nuclear magnetic resonance (NMR) spectroscopy allows scientists to study protein
      structure, dynamics and interactions in solution. A necessary first step for such
      applications is determining the resonance assignment, mapping spectral data to
      atoms and residues in the primary sequence. Automated resonance assignment
      algorithms rely on information regarding connectivity (e.g., through-bond atomic
      interactions) and amino acid type, typically using the former to determine
      strings of connected residues and the latter to map those strings to positions in
      the primary sequence. Significant ambiguity exists in both connectivity and amino
      acid type information. This paper focuses on the information content available in
      connectivity alone and develops a novel random-graph theoretic framework and
      algorithm for connectivity-driven NMR sequential assignment. Our random graph
      model captures the structure of chemical shift degeneracy, a key source of
      connectivity ambiguity. We then give a simple and natural randomized algorithm
      for finding optimal assignments as sets of connected fragments in NMR graphs. The
      algorithm naturally and efficiently reuses substrings while exploring
      connectivity choices; it overcomes local ambiguity by enforcing global
      consistency of all choices. By analyzing our algorithm under our random graph
      model, we show that it can provably tolerate relatively large ambiguity while
      still giving expected optimal performance in polynomial time. We present results
      from practical applications of the algorithm to experimental datasets from a
      variety of proteins and experimental set-ups. We demonstrate that our approach is
      able to overcome significant noise and local ambiguity in identifying significant
      fragments of sequential assignments.

PMID- 16108705
TI  - Learning multiple evolutionary pathways from cross-sectional data.
AB  - We introduce a mixture model of trees to describe evolutionary processes that are
      characterized by the ordered accumulation of permanent genetic changes. The basic
      building block of the model is a directed weighted tree that generates a
      probability distribution on the set of all patterns of genetic events. We present
      an EM-like algorithm for learning a mixture model of K trees and show how to
      determine K with a maximum likelihood approach. As a case study, we consider the
      accumulation of mutations in the HIV-1 reverse transcriptase that are associated
      with drug resistance. The fitted model is statistically validated as a density
      estimator, and the stability of the model topology is analyzed. We obtain a
      generative probabilistic model for the development of drug resistance in HIV that
      agrees with biological knowledge. Further applications and extensions of the
      model are discussed.

PMID- 16108706
TI  - Large multiple organism gene finding by collapsed Gibbs sampling.
AB  - The Gibbs sampling method has been widely used for sequence analysis after it was
      successfully applied to the problem of identifying regulatory motif sequences
      upstream of genes. Since then, numerous variants of the original idea have
      emerged: however, in all cases the application has been to finding short motifs
      in collections of short sequences (typically less than 100 nucleotides long). In
      this paper, we introduce a Gibbs sampling approach for identifying genes in
      multiple large genomic sequences up to hundreds of kilobases long. This approach
      leverages the evolutionary relationships between the sequences to improve the
      gene predictions, without explicitly aligning the sequences. We have applied our
      method to the analysis of genomic sequence from 14 genomic regions, totaling
      roughly 1.8 Mb of sequence in each organism. We show that our approach compares
      favorably with existing ab initio approaches to gene finding, including pairwise
      comparison based gene prediction methods which make explicit use of alignments.
      Furthermore, excellent performance can be obtained with as little as four
      organisms, and the method overcomes a number of difficulties of previous
      comparison based gene finding approaches: it is robust with respect to genomic
      rearrangements, can work with draft sequence, and is fast (linear in the number
      and length of the sequences). It can also be seamlessly integrated with Gibbs
      sampling motif detection methods.

PMID- 16108707
TI  - Protein similarity from knot theory: geometric convolution and line weavings.
AB  - Shape similarity is one of the most elusive and intriguing questions of nature
      and mathematics. Proteins provide a rich domain in which to test theories of
      shape similarity. Proteins can match at different scales and in different
      arrangements. Sometimes the detection of common local structure is sufficient to
      infer global alignment of two proteins; at other times it provides false
      information. Proteins with very low sequence identity may share large
      substructures, or perhaps just a central core. There are even examples of
      proteins with nearly identical primary sequences in which alpha-helices have
      become beta-sheets. Shape similarity can be formulated (i) in terms of global
      metrics, such as RMSD or Hausdorff distance, (ii) in terms of subgraph
      isomorphisms, such as the detection of shared substructures with similar relative
      locations, or (iii) purely topologically, in terms of structure preserving
      transformations. Existing protein structure detection programs are built on the
      first two types of similarity. The third forms the foundations of knot theory.
      The thesis of this paper is this: Protein similarity detection leads naturally to
      algorithms operating at the metric, relational, and isotopic scales. The paper
      introduces a definition of similarity based on atomic motions that preserve local
      backbone topology without incurring significant distance errors. Such motions are
      motivated by the physical requirements for rearranging subsequences of a protein.
      Similarity detection then seeks rigid body motions able to overlay pairs of
      substructures, each related by a substructure-preserving motion, without
      necessarily requiring global structure preservation. This definition is general
      enough to span a wide range of questions: One can ask for full rearrangement of
      one protein into another while preserving global topology, as in drug design; or
      one can ask for rearrangements of sets of smaller substructures, preserving local
      but not global topology, as in protein evolution. In the appendix, we exhibit an
      algorithm for answering the general rearrangement question. That algorithm has
      the complexity of robot motion planning. In the text, we consider a more common
      case in which one seeks protein similarity by rearrangements of relatively short
      peptide segments. We exhibit two algorithms, one based on writhing numbers and
      one based on line weavings. The algorithms have time complexities O(n (4)) and
      O(s (11)), respectively, where n is the maximum number of residues in the
      proteins being compared and s is the number of secondary structure elements. In
      practice, the running times were nearly interactive. We report results obtained
      with a dozen pairs of proteins, exhibiting a range of typical features.

PMID- 16108708
TI  - Identifying conserved gene clusters in the presence of homology families.
AB  - The study of conserved gene clusters is important for understanding the forces
      behind genome organization and evolution, as well as the function of individual
      genes or gene groups. In this paper, we present a new model and algorithm for
      identifying conserved gene clusters from pairwise genome comparison. This
      generalizes a recent model called "gene teams." A gene team is a set of genes
      that appear homologously in two or more species, possibly in a different order
      yet with the distance of adjacent genes in the team for each chromosome always no
      more than a certain threshold. We remove the constraint in the original model
      that each gene must have a unique occurrence in each chromosome and thus allow
      the analysis on complex prokaryotic or eukaryotic genomes with extensive
      paralogs. Our algorithm analyzes a pair of chromosomes in O(mn) time and uses
      O(m+n) space, where m and n are the number of genes in the respective
      chromosomes. We demonstrate the utility of our methods by studying two bacterial
      genomes, E. coli K-12 and B. subtilis. Many of the teams identified by our
      algorithm correlate with documented E. coli operons, while several others match
      predicted operons, previously suggested by computational techniques. Our
      implementation and data are publicly available at euler.slu.edu/ approximately
      goldwasser/homologyteams/.

PMID- 16108709
TI  - Comparing graph representations of protein structure for mining family-specific
      residue-based packing motifs.
AB  - We find recurring amino-acid residue packing patterns, or spatial motifs, that
      are characteristic of protein structural families, by applying a novel frequent
      subgraph mining algorithm to graph representations of protein three-dimensional
      structure. Graph nodes represent amino acids, and edges are chosen in one of
      three ways: first, using a threshold for contact distance between residues;
      second, using Delaunay tessellation; and third, using the recently developed
      almost-Delaunay edges. For a set of graphs representing a protein family from the
      Structural Classification of Proteins (SCOP) database, subgraph mining typically
      identifies several hundred common subgraphs corresponding to spatial motifs that
      are frequently found in proteins in the family but rarely found outside of it. We
      find that some of the large motifs map onto known functional regions in two
      protein families explored in this study, i.e., serine proteases and kinases. We
      find that graphs based on almost-Delaunay edges significantly reduce the number
      of edges in the graph representation and hence present computational advantage,
      yet the patterns extracted from such graphs have a biological interpretation
      approximately equivalent to that of those extracted from distance based graphs.

PMID- 16108710
TI  - Checking homogeneity of motifs' distribution in heterogenous sequences.
AB  - Studying the distribution of a motif along sequences may help in the
      understanding of its biological function, or to detect regions of interest. A
      statistical model is needed to assess the significance of the observed
      distribution. We propose a heterogenous compound Poisson process to model the
      possibility of overlap between occurrences and some heterogeneity of the sequence
      known a priori. The estimation procedure of the parameters is described and tests
      of homogenous sub-models are proposed. We also consider the detection of rich
      regions using either cumulated distances or moving intervals, via a
      homogenization technique. Illustrations of the method are given with applications
      to bacterial genomes.

PMID- 16108711
TI  - Finding motifs with insufficient number of strong binding sites.
AB  - A molecule called transcription factor usually binds to a set of promoter
      sequences of coexpressed genes. As a result, these promoter sequences contain
      some short substrings, or binding sites, with similar patterns. The motif
      discovering problem is to find these similar patterns and motifs in a set of
      sequences. Most existing algorithms find the motifs based on strong-signal
      sequences only (i.e., those containing binding sites very similar to the motif).
      In this paper, we use a probability matrix to represent a motif to calculate the
      minimum total number of binding sites required to be in the input dataset in
      order to confirm that the discovered motifs are not artifacts. Next, we introduce
      a more general and realistic energy-based model, which considers all sequences
      with varying degrees of binding strength to the transcription factors (as
      measured experimentally). By treating sequences with varying degrees of binding
      strength, we develop a heuristic algorithm called EBMF (Energy-Based Motif
      Finding Algorithm) to find the motif, which can handle sequences ranging from
      those that contain more than one binding site to those that contain none. EBMF
      can find motifs for datasets that do not even have the required minimum number of
      binding sites as previously derived. EBMF compares favorably with common motif
      finding programs AlignACE and MEME. In particular, for some simulated and real
      datasets, EBMF finds the motif when both AlignACE and MEME fail to do so.

PMID- 16108712
TI  - A class of edit kernels for SVMs to predict translation initiation sites in
      eukaryotic mRNAs.
AB  - The prediction of translation initiation sites (TISs) in eukaryotic mRNAs has
      been a challenging problem in computational molecular biology. In this paper, we
      present a new algorithm to recognize TISs with a very high accuracy. Our
      algorithm includes two novel ideas. First, we introduce a class of new sequence
      similarity kernels based on string editing, called edit kernels, for use with
      support vector machines (SVMs) in a discriminative approach to predict TISs. The
      edit kernels are simple and have significant biological and probabilistic
      interpretations. Although the edit kernels are not positive definite, it is easy
      to make the kernel matrix positive definite by adjusting the parameters. Second,
      we convert the region of an input mRNA sequence downstream to a putative TIS into
      an amino acid sequence before applying SVMs to avoid the high redundancy in the
      genetic code. The algorithm has been implemented and tested on previously
      published data. Our experimental results on real mRNA data show that both ideas
      improve the prediction accuracy greatly and that our method performs
      significantly better than those based on neural networks and SVMs with polynomial
      kernels or Salzberg kernels.

PMID- 16108713
TI  - Computing the minimum recombinant haplotype configuration from incomplete
      genotype data on a pedigree by integer linear programming.
AB  - We study the problem of reconstructing haplotype configurations from genotypes on
      pedigree data with missing alleles under the Mendelian law of inheritance and the
      minimum-recombination principle, which is important for the construction of
      haplotype maps and genetic linkage/association analyses. Our previous results
      show that the problem of finding a minimum-recombinant haplotype configuration
      (MRHC) is in general NP-hard. This paper presents an effective integer linear
      programming (ILP) formulation of the MRHC problem with missing data and a branch
      and-bound strategy that utilizes a partial order relationship and some other
      special relationships among variables to decide the branching order. Nontrivial
      lower and upper bounds on the optimal number of recombinants are introduced at
      each branching node to effectively prune the search tree. When multiple solutions
      exist, a best haplotype configuration is selected based on a maximum likelihood
      approach. The paper also shows for the first time how to incorporate marker
      interval distance into a rule-based haplotyping algorithm. Our results on
      simulated data show that the algorithm could recover haplotypes with 50 loci from
      a pedigree of size 29 in seconds on a Pentium IV computer. Its accuracy is more
      than 99.8% for data with no missing alleles and 98.3% for data with 20% missing
      alleles in terms of correctly recovered phase information at each marker locus. A
      comparison with a statistical approach SimWalk2 on simulated data shows that the
      ILP algorithm runs much faster than SimWalk2 and reports better or comparable
      haplotypes on average than the first and second runs of SimWalk2. As an
      application of the algorithm to real data, we present some test results on
      reconstructing haplotypes from a genome-scale SNP dataset consisting of 12
      pedigrees that have 0.8% to 14.5% missing alleles.

PMID- 16108714
TI  - A novel ensemble-based scoring and search algorithm for protein redesign and its
      application to modify the substrate specificity of the gramicidin synthetase a
      phenylalanine adenylation enzyme.
AB  - Realization of novel molecular function requires the ability to alter molecular
      complex formation. Enzymatic function can be altered by changing enzyme-substrate
      interactions via modification of an enzyme's active site. A redesigned enzyme may
      either perform a novel reaction on its native substrates or its native reaction
      on novel substrates. A number of computational approaches have been developed to
      address the combinatorial nature of the protein redesign problem. These
      approaches typically search for the global minimum energy conformation among an
      exponential number of protein conformations. We present a novel algorithm for
      protein redesign, which combines a statistical mechanics-derived ensemble-based
      approach to computing the binding constant with the speed and completeness of a
      branch-and-bound pruning algorithm. In addition, we developed an efficient
      deterministic approximation algorithm, capable of approximating our scoring
      function to arbitrary precision. In practice, the approximation algorithm
      decreases the execution time of the mutation search by a factor of ten. To test
      our method, we examined the Phe-specific adenylation domain of the nonribosomal
      peptide synthetase gramicidin synthetase A (GrsA-PheA). Ensemble scoring, using a
      rotameric approximation to the partition functions of the bound and unbound
      states for GrsA-PheA, is first used to predict binding of the wildtype protein
      and a previously described mutant (selective for leucine), and second, to switch
      the enzyme specificity toward leucine, using two novel active site sequences
      computationally predicted by searching through the space of possible active site
      mutations. The top scoring in silico mutants were created in the wetlab and
      dissociation/binding constants were determined by fluorescence quenching. These
      tested mutations exhibit the desired change in specificity from Phe to Leu. Our
      ensemble-based algorithm, which flexibly models both protein and ligand using
      rotamer-based partition functions, has application in enzyme redesign, the
      prediction of protein-ligand binding, and computer-aided drug design.

PMID- 16108715
TI  - Finding anchors for genomic sequence comparison.
AB  - Recent sequencing of the human and other mammalian genomes has brought about the
      necessity to align them, to identify and characterize their commonalities and
      differences. Programs that align whole genomes generally use a seed-and-extend
      technique, starting from exact or near-exact matches and selecting a reliable
      subset of these, called anchors, and then filling in the remaining portions
      between the anchors using a combination of local and global alignment algorithms,
      but their choices for the parameters so far have been primarily heuristic. We
      present a statistical framework and practical methods for selecting a set of
      matches that is both sensitive and specific and can constitute a reliable set of
      anchors for a one-to-one mapping of two genomes from which a whole-genome
      alignment can be built. Starting from exact matches, we introduce a novel per
      base repeat annotation, the Z-score, from which noise and repeat filtering
      conditions are explored. Dynamic programming-based chaining algorithms are also
      evaluated as context-based filters. We apply the methods described here to the
      comparison of two progressive assemblies of the human genome, NCBI build 28 and
      build 34 (www.genome.ucsc.edu), and show that a significant portion of the two
      genomes can be found in selected exact matches, with very limited amount of
      sequence duplication.

PMID- 16108716
TI  - Wrap-and-Pack: a new paradigm for beta structural motif recognition with
      application to recognizing beta trefoils.
AB  - A method is presented that uses beta-strand interactions at both the sequence and
      the atomic level, to predict beta-structural motifs of protein sequences. A
      program called Wrap-and- Pack implements this method and is shown to recognize
      beta-trefoils, an important class of globular beta-structures, in the Protein
      Data Bank with 92% specificity and 92.3% sensitivity in cross-validation. It is
      demonstrated that Wrap-and-Pack learns each of the ten known SCOP beta-trefoil
      families, when trained primarily on beta-structures that are not beta-trefoils,
      together with three-dimensional structures of known beta-trefoils from outside
      the family. Wrap-and-Pack also predicts many proteins of unknown structure to be
      beta-trefoils. The computational method used here may generalize to other beta
      structures for which strand topology and profiles of residue accessibility are
      well conserved.

PMID- 16108717
TI  - Reconstructing reticulate evolution in species-theory and practice.
AB  - We present new methods for reconstructing reticulate evolution of species due to
      events such as horizontal transfer or hybrid speciation; both methods are based
      upon extensions of Wayne Maddison's approach in his seminal 1997 paper. Our first
      method is a polynomial time algorithm for constructing phylogenetic networks from
      two gene trees contained inside the network. We allow the network to have an
      arbitrary number of reticulations, but we limit the reticulation in the network
      so that the cycles in the network are node-disjoint ("galled"). Our second method
      is a polynomial time algorithm for constructing networks with one reticulation,
      where we allow for errors in the estimated gene trees. Using simulations, we
      demonstrate improved performance of this method over both NeighborNet and
      Maddison's method.

PMID- 16108718
TI  - Chromosomal breakpoint reuse in genome sequence rearrangement.
AB  - In order to apply gene-order rearrangement algorithms to the comparison of genome
      sequences, Pevzner and Tesler bypass gene finding and ortholog identification and
      use the order of homologous blocks of unannotated sequence as input. The method
      excludes blocks shorter than a threshold length. Here we investigate possible
      biases introduced by eliminating short blocks, focusing on the notion of
      breakpoint reuse introduced by these authors. Analytic and simulation methods
      show that reuse is very sensitive to the proportion of blocks excluded. As is
      pertinent to the comparison of mammalian genomes, this exclusion risks
      randomizing the comparison partially or entirely.

PMID- 16108719
TI  - A discriminative model for identifying spatial cis-regulatory modules.
AB  - Transcriptional regulation is mediated by the coordinated binding of
      transcription factors to the upstream regions of genes. In higher eukaryotes, the
      binding sites of cooperating transcription factors are organized into short
      sequence units, called cis-regulatory modules. In this paper, we propose a method
      for identifying modules of transcription factor binding sites in a set of co
      regulated genes, using only the raw sequence data as input. Our method is based
      on a novel probabilistic model that describes the mechanism of cis-regulation,
      including the binding sites of cooperating transcription factors, the
      organization of these binding sites into short sequence modules, and the
      regulation of a gene by its modules. We show that our method is successful in
      discovering planted modules in simulated data and known modules in yeast. More
      importantly, we applied our method to a large collection of human gene sets and
      found 83 significant cis-regulatory modules, which included 36 known motifs and
      many novel ones. Thus, our results provide one of the first comprehensive
      compendiums of putative cis-regulatory modules in human.

PMID- 16108720
TI  - Identification of protein complexes by comparative analysis of yeast and
      bacterial protein interaction data.
AB  - Mounting evidence shows that many protein complexes are conserved in evolution.
      Here we use conservation to find complexes that are common to the yeast S.
      cerevisiae and the bacteria H. pylori. Our analysis combines protein interaction
      data that are available for each of the two species and orthology information
      based on protein sequence comparison. We develop a detailed probabilistic model
      for protein complexes in a single species and a model for the conservation of
      complexes between two species. Using these models, one can recast the question of
      finding conserved complexes as a problem of searching for heavy subgraphs in an
      edge- and node-weighted graph, whose nodes are orthologous protein pairs. We
      tested this approach on the data currently available for yeast and bacteria and
      detected 11 significantly conserved complexes. Several of these complexes match
      very well with prior experimental knowledge on complexes in yeast only and serve
      for validation of our methodology. The complexes suggest new functions for a
      variety of uncharacterized proteins. By identifying a conserved complex whose
      yeast proteins function predominantly in the nuclear pore complex, we propose
      that the corresponding bacterial proteins function as a coherent cellular
      membrane transport system. We also compare our results to two alternative methods
      for detecting complexes and demonstrate that our methodology obtains a much
      higher specificity.

PMID- 16108721
TI  - Designing multiple simultaneous seeds for DNA similarity search.
AB  - The challenge of similarity search in massive DNA sequence databases has inspired
      major changes in BLAST-style alignment tools, which accelerate search by
      inspecting only pairs of sequences sharing a common short "seed," or pattern of
      matching residues. Some of these changes raise the possibility of improving
      search performance by probing sequence pairs with several distinct seeds, any one
      of which is sufficient for a seed match. However, designing a set of seeds to
      maximize their combined sensitivity to biologically meaningful sequence
      alignments is computationally difficult, even given recent advances in designing
      single seeds. This work describes algorithmic improvements to seed design that
      address the problem of designing a set of n seeds to be used simultaneously. We
      give a new local search method to optimize the sensitivity of seed sets. The
      method relies on efficient incremental computation of the probability that an
      alignment contains a match to a seed pi, given that it has already failed to
      match any of the seeds in a set Pi. We demonstrate experimentally that multi-seed
      designs, even with relatively few seeds, can be significantly more sensitive than
      even optimized single-seed designs.

PMID- 16108722
TI  - Using motion planning to study RNA folding kinetics.
AB  - We propose a novel, motion planning based approach to approximately map the
      energy landscape of an RNA molecule. A key feature of our method is that it
      provides a sparse map that captures the main features of the energy landscape
      which can be analyzed to compute folding kinetics. Our method is based on
      probabilistic roadmap motion planners that we have previously successfully
      applied to protein folding. In this paper, we provide evidence that this approach
      is also well suited to RNA. We compute population kinetics and transition rates
      on our roadmaps using the master equation for a few moderately sized RNA and show
      that our results compare favorably with results of other existing methods.

PMID- 16108723
TI  - Stochastic models inspired by hybridization theory for short oligonucleotide
      arrays.
AB  - High density oligonucleotide expression arrays are a widely used tool for the
      measurement of gene expression on a large scale. Affymetrix GeneChip arrays
      appear to dominate this market. These arrays use short oligonucleotides to probe
      for genes in an RNA sample. Due to optical noise, nonspecific hybridization,
      probe-specific effects, and measurement error, ad hoc measures of expression that
      summarize probe intensities can lead to imprecise and inaccurate results. Various
      researchers have demonstrated that expression measures based on simple
      statistical models can provide great improvements over the ad hoc procedure
      offered by Affymetrix. Recently, physical models based on molecular hybridization
      theory have been proposed as useful tools for prediction of, for example,
      nonspecific hybridization. These physical models show great potential in terms of
      improving existing expression measures. In this paper, we suggest that the system
      producing the measured intensities is too complex to be fully described with
      these relatively simple physical models, and we propose empirically motivated
      stochastic models that complement the above-mentioned molecular hybridization
      theory to provide a comprehensive description of the data. We discuss how the
      proposed model can be used to obtain improved measures of expression useful for
      the data analysts.

PMID- 16108724
TI  - Finding short DNA motifs using permuted Markov models.
AB  - Many short DNA motifs, such as transcription factor binding sites (TFBS) and
      splice sites, exhibit strong local as well as nonlocal dependence. We introduce
      permuted variable length Markov models (PVLMM) which could capture the
      potentially important dependencies among positions and apply them to the problem
      of detecting splice and TFB sites. They have been satisfactory from the viewpoint
      of prediction performance and also give ready biological interpretations of the
      sequence dependence observed. The issue of model selection is also studied.

PMID- 16108726
TI  - The guanylate-binding proteins (GBPs): proinflammatory cytokine-induced members
      of the dynamin superfamily with unique GTPase activity.
AB  - The guanylate-binding proteins (GBPs) were first identified in the late 1970s,
      and within a short period of time, investigators were aware that GBPs possessed
      unique properties, in particular the ability to bind GMP agarose. Since then,
      much study has gone into understanding their mechanism of induction by
      interferons (IFNs) and other cytokines, and they have been used extensively as
      markers for IFN responsiveness in both cells and organisms. In time, we learned
      that GBPs had the unusual ability to hydrolyze GTP to both GDP and GMP. More
      recently, we have begun to appreciate their novel structure, one that suggests
      unique mechanisms of GTP binding and hydrolysis and unique forms of regulation.
      In addition, we have begun to unravel some of their functions and to separate
      these function into those functions that do and those that do not require GTPase
      activity.

PMID- 16108727
TI  - Lack of IFN-gamma production in response to antigenic stimulation in human IFN
      tau-treated lymphocytes.
AB  - Interferon-tau (IFN-tau) is a type I IFN responsible for maternal recognition of
      the fetus in ruminants. In addition to its physiologic role, IFN-tau also
      inhibits HIV replication in human lymphocytes and macrophages and displays
      immunomodulatory effects but lacks the toxicity associated with other type I
      IFNs. Human IFN-alpha promotes a Th1 response, whereas IFN-tau has anti
      inflammatory properties, inducing the production of Th2 cytokines in murine
      models of experimental autoimmune encephalitis (EAE) or fetal loss. We compared
      the effects of ovine IFN-tau (OvIFN-tau) and human IFN-alpha (HuIFN-alpha) on
      cytokine mRNA and protein production in human peripheral blood mononuclear cells
      (PBMCs) activated with a recall antigen, such as purified protein derivative
      (PPD) of tuberculin or with a proinflammatory stimulus, such as
      lipopolysaccharide (LPS). In both cases, IFN-alpha increased IFN-gamma
      production, whereas IFN-tau did not and thereby promoted Th2 cytokine production.
      This original property renders IFN-tau a potential candidate for therapeutic
      applications in immune disorders, such as multiple sclerosis (MS), but its
      therapeutic use in the treatment of HIV infection should be considered with
      caution.

PMID- 16108728
TI  - Clinical role of serum and tissue matrix metalloprotease-9 expression in chronic
      HCV patients treated with pegylated IFN-alpha2b and ribavirin.
AB  - In chronic hepatitis C, the main goal of antiviral therapies is to block viral
      replication and to slow down the development of fibrosis. In this study, a
      decrease in matrix metalloprotease-9 (MMP-9) but not of MMP-2 and the tissue
      inhibitors of MMP (TIMP-1 and TMP-2) was observed in the plasma of chronic
      hepatitis C patients at the end of the follow-up period after ribavirin plus
      interferon-alpha2b (PEG-IFN-alpha2b) treatment in sustained virologic responders
      but not in nonresponders. Consistently, similar results are observed by
      immunofluorescence and real-time PCR in tissue specimens collected before and
      after therapy from the same patients in whom both Kupffer cells and hepatocytes
      express MMP-9. In conclusion, our results show that MMP-9 decreases in responder
      patients both in the serum and in the liver after therapy. Further studies are
      needed to investigate this new possible therapeutic activity of PEG-IFN-alpha2b.

PMID- 16108729
TI  - Ability of orally administered IFN-alpha-containing transgenic potato extracts to
      inhibit Listeria monocytogenes infection.
AB  - Type I interferons (IFN-alpha/beta) were originally thought to be antiviral
      cytokines, but it has recently been reported that they also play an important
      role in potentiating innate and adaptive immune responses. Moreover, several
      studies have shown that the oral administration of type I IFN ameliorates various
      biologic activities. Here, we studied the ability of orally administered IFN
      alpha to protect mice from systemic Listeria monocytogenes infection. Daily oral
      administration of purified natural IFN-alpha at a concentration of 1000
      international units (IU)/20 microl reduced the bacterial burden in infected
      organs. We also examined the protective effect of IFN-alpha expressed in
      transgenic potato plants. A much lower concentration of IFN-alpha (20 IU/ 20
      microl) in the plant extracts was almost as protective as much higher
      concentrations of purified natural IFN-alpha. Our observations indicate that
      transgenic cytokine-expressing plants can be used prophylactically as edible
      pharmaceuticals to enhance systemic defense responses in humans and animals.

PMID- 16108730
TI  - A genomic analysis of chicken cytokines and chemokines.
AB  - As most mechanisms of adaptive immunity evolved during the divergence of
      vertebrates, the immune systems of extant vertebrates represent different
      successful variations on the themes initiated in their earliest common ancestors.
      The genes involved in elaborating these mechanisms have been subject to
      exceptional selective pressures in an arms race with highly adaptable pathogens,
      resulting in highly divergent sequences of orthologous genes and the gain and
      loss of members of gene families as different species find different solutions to
      the challenge of infection. Consequently, it has been difficult to transfer to
      the chicken detailed knowledge of the molecular mechanisms of the mammalian
      immune system and, thus, to enhance the already significant contribution of
      chickens toward understanding the evolution of immunity. The availability of the
      chicken genome sequence provides the opportunity to resolve outstanding questions
      concerning which molecular components of the immune system are shared between
      mammals and birds and which represent their unique evolutionary solutions. We
      have integrated genome data with existing knowledge to make a new comparative
      census of members of cytokine and chemokine gene families, distinguishing the
      core set of molecules likely to be common to all higher vertebrates from those
      particular to these 300 million-year-old lineages. Some differences can be
      explained by the different architectures of the mammalian and avian immune
      systems. Chickens lack lymph nodes and also the genes for the lymphotoxins and
      lymphotoxin receptors. The lack of functional eosinophils correlates with the
      absence of the eotaxin genes and our previously reported observation that
      interleukin- 5 (IL-5) is a pseudogene. To summarize, in the chicken genome, we
      can identify the genes for 23 ILs, 8 type I interferons (IFNs), IFN-gamma, 1
      colony-stimulating factor (GM-CSF), 2 of the 3 known transforming growth factors
      (TGFs), 24 chemokines (1 XCL, 14 CCL, 8 CXCL, and 1 CX3CL), and 10 tumor necrosis
      factor superfamily (TNFSF) members. Receptor genes present in the genome suggest
      the likely presence of 2 other ILs, 1 other CSF, and 2 other TNFSF members.

PMID- 16108731
TI  - Immunomodulatory effects of IFN-beta1a treatment alone or associated with
      pentoxifylline in patients with relapsing-remitting multiple sclerosis (RRMS).
AB  - Interferon-beta1a (IFN-beta1a) and pentoxifylline (PTX) are reported to be active
      in relapsing-remitting multiple sclerosis (RRMS), but the mechanisms are not
      completely understood. In two groups of RRMS patients, we studied the phenotype
      of peripheral lymphocytes and the level of several cytokines both in sera and in
      supernatants of activated peripheral blood mononuclear cells (PBMC) before and
      after 8 months of therapy with IFN-beta1a alone or associated with PTX. Our data
      indicate that patients with RRMS, treated with IFN-beta1a, exhibited a
      significant increase in CD4(+)CD25(++) T suppressor cells, accompanied by a
      significant decrease in cytotoxic lymphocytes (CD8(+)CD28(-) and natural killer
      [NK] cells) and IFN-gamma production, which could both contribute to an
      explanation of the previously described beneficial effects of IFN-beta treatment
      in MS. The addition of PTX to IFN-beta1a treatment did not modify the
      immunomodulatory effects obtained with IFN-beta1a alone. Future studies are
      needed to demonstrate which immunologic parameters correlate with the clinical
      benefit of IFN-beta1a treatment.

PMID- 16108732
TI  - Hematopoietic progenitor cell mobilization in mice by sustained delivery of
      granulocyte colony-stimulating factor.
AB  - The objective of these studies was to determine the effect of sustained delivery
      of growth factors (GFs) on hematopoietic progenitor cells (HPCs) in mice. In
      these studies, granulocyte colony-stimulating factor (G-CSF) was administered
      using the poloxamer-based matrix, ProGelz (PG) and G-CSF, and pharmacokinetics
      (PKs) and HPC mobilization was assessed. A single injection of G-CSF formulated
      in PG (17% poloxamer-407 and 5% hydroxypropyl methylcellulose [HPMC])
      administered to BALB/c mice mobilized HPC significantly more rapidly to the
      spleen, but not the blood, than multiple injections of saline-formulated G-CSF.
      Two days after a single injection of PG G-CSF, the frequency of colony-forming
      unit-culture (CFU-c) in the spleen was increased 289-fold compared with an 8-fold
      increase after 2 days of twice-daily injections of saline-formulated G-CSF.
      Indeed, 4 days of twice-daily G-CSF injections were required to achieve the same
      level of HPC mobilization. In contrast, a similar mobilization of HPC to the
      blood was observed between PG and saline-formulated G-CSF. The mechanism for the
      accelerated and increased mobilization to the spleen by the PG-formulation of G
      CSF is due, in part, to its increased bioavailability (>1.5-fold), T(max) (6
      fold), and prolonged elimination (Tbeta) half-life (>3-fold) as compared with a
      saline formulation. In addition, we observed a more rapid trafficking of the PG G
      CSF to the marrow, which could also facilitate mobilization.

PMID- 16108734
TI  - Oxidative stress markers after laparoscopic and open cholecystectomy.
AB  - BACKGROUND: Surgical injury is associated with oxidative stress, often due to
      ischemia/reperfusion injury. During laparoscopy, increased intra-abdominal
      pressure caused by pneumoperitoneum may cause splanchnic ischemia followed by
      reperfusion due to deflation. We measured several markers of oxidative stress in
      patients undergoing laparoscopic cholecystectomy (LC) versus open cholecystectomy
      (OC) to find if these surgical procedures result in different patterns of
      oxidative stress. METHODS: This prospective study enrolled 43 patients with
      symptomatic cholelithiasis, of whom 21 underwent open, and 22 laparoscopic,
      cholecystectomy. Twenty healthy adults comprised the control group. Total
      antioxidant status (TAS), superoxide dismutase (SOD), endogenous peroxide level
      (POX), oxidized low density lipoprotein (oLDL) autoantibodies (oLAb), and
      neopterin were measured preoperatively and on postoperative days 1, 3, and 7.
      RESULTS: POX values decreased significantly on postoperative day 1 in the OC
      (P<0.01), but not in the LC, group. On postoperative day 7, POX values were
      higher than preoperatively in both groups (P<0.01) with no difference between the
      LC and OC groups. Significant postoperative elevations of oLAb and neopterin
      levels were observed only on postoperative day 7 in the OC group. There were no
      changes of oLAb and neopterin levels in the LC group. TAS and SOD levels did not
      change after either LC or OC. CONCLUSION: Cholecystectomy, either open or
      laparoscopic, caused only moderate oxidative stress. Open cholecystectomy caused
      changes of oLAb and neopterin, suggesting more severe oxidative stress, and a
      possible role of reactive oxygen species in the healing of the laparotomic wound.

PMID- 16108735
TI  - Laparoscopic appendectomy using the LigaSure Vessel Sealing System.
AB  - BACKGROUND: Laparoscopic appendectomy is increasingly being employed to treat
      acute appendicitis. The aim of the present study was to evaluate the efficacy and
      safety of the LigaSure Vessel Sealing System (Valleylab, Boulder, CO) in
      laparoscopic appendectomy. PATIENTS AND METHODS: Laparoscopic appendectomy was
      performed using the LigaSure system in 15 patients who had a preoperative
      diagnosis of acute appendicitis. RESULTS: In two patients, the operation was
      converted to open appendectomy. The mean operative time was 47 minutes (range, 22
      120 minutes). There was no evidence of any complications related to the use of
      the LigaSure system. Neither surgical endoclips nor an endostapler were used in
      any patient. CONCLUSION: Laparoscopic appendectomy using the LigaSure system is a
      safe and efficient procedure for acute appendicitis. Use of the LigaSure system
      in laparoscopic appendectomy may simplify the operative procedure and reduce the
      operative time.

PMID- 16108736
TI  - Elective laparoscopic cholecystectomy for symptomatic gallstone disease in
      patients receiving anticoagulant therapy.
AB  - BACKGROUND: The safety of laparoscopic cholecystectomy (LC) has been proven in
      patients with several pre-existing clinical conditions. This study was conducted
      to evaluate the applicability and safety of elective LC in patients with pre
      existing cardiovascular conditions who were receiving anticoagulant treatment.
      PATIENTS AND METHODS: Between January 1998 and December 2002, 33 patients
      preoperatively receiving long-term anticoagulant therapy for pre-existing disease
      were scheduled to undergo elective LC for symptomatic gallstone disease in our
      laparoendoscopic unit. The study group included 19 patients with one valve
      replacement (57.6%), 1 patient (3%) with two valves replaced, and 1 patient (3%)
      with three cardiac valves replaced. There were also 9 patients (27.3%) suffering
      from chronic atrial fibrillation, 1 patient (3%) with a history of deep vein
      thrombosis, 1 patient with a history of pulmonary embolism, and 1 patient with
      dilated cardiomyopathy and systemic lupus erythematosous (SLE). Thirty-three non
      anticoagulated patients matched for age and sex who were scheduled for elective
      LC in our department during the same period served as the control group. RESULTS:
      There was no intraoperative or postoperative mortality or morbidity in our
      series. The mean duration of the LC did not differ significantly between the
      anticoagulated and control groups (63.6 minutes vs. 64.9 minutes, P=0.643). All
      anticoagulated patients were mobilized by postoperative day 1 and were discharged
      from the hospital in a mean 3.6+/-0.8 days (median, 3 days; range, 3-6 days)
      after an uneventful postoperative course. The length of stay was significantly
      longer in the anticoagulated group of patients (3.6 days vs. 1.5 days in the
      control group, P<0.001). CONCLUSION: Elective LC can be performed safely in
      patients under anticoagulant therapy for severe pre-existing cardiovascular
      disease, as long as their cardiopulmonary and coagulation parameters are
      carefully individualized and adjusted.

PMID- 16108737
TI  - Comparison of the efficacy of the pulsed bipolar system and conventional bipolar
      electrosurgery in laparoscopically assisted vaginal hysterectomy.
AB  - BACKGROUND: We compared the safety and effectiveness of the pulsed bipolar system
      (PlasmaKinetic; Gyrus Medical, Maple Grove, MN) and conventional electrosurgery
      (Kleppinger bipolar forceps; Richard Wolf Instruments, Vernon Hills, IL) in
      laparoscopically assisted vaginal hysterectomy (LAVH). PATIENTS AND METHODS: In
      this prospective, nonrandomized study, 62 women with benign gynecologic diseases
      scheduled for LAVH were divided into two groups: one group underwent LAVH with
      the pulsed bipolar system and the second group underwent LAVH with conventional
      electrosurgery. Outcome measures for both groups were compared in terms of length
      of operative time, amount of blood loss, requirement of blood transfusion, and
      length of hospital stay. RESULTS: The mean operative time (87.6+/-28.1 minutes
      vs. 93.4+/-20.2 minutes, P=0.368), blood loss (196.8+/-143.7 mL vs. 253.2+/-125.8
      mL, P=0.105), and blood transfusion rate (3.2% vs. 6.5%, P=1.0) were slightly
      greater in the conventional electrosurgery group than those in the pulsed bipolar
      system group, although these differences were not statistically significant. The
      mean length of hospital stay was similar in both groups (3 days). No patients
      developed serious complications related either to conventional electrosurgery or
      to the pulsed bipolar system. CONCLUSION: Our findings indicate that the pulsed
      bipolar system is as safe and effective as conventional electrosurgery, and may
      offer an alternative option for patients undergoing LAVH.

PMID- 16108738
TI  - Laparoscopy-assisted exploration of obscure gastrointestinal bleeding after
      capsule endoscopy: the Korean experience.
AB  - BACKGROUND: Obscure gastrointestinal bleeding (OGB) is generally defined as
      recurrent acute or chronic bleeding for which no source has been identified by
      routine radiologic and endoscopic examination. The aim of this study was to
      report our early experiences detecting small bowel bleeding by capsule endoscopy
      (CE) and the results of laparoscopy assisted surgery for OGB. MATERIALS AND
      METHODS: Seventy-five patients with OGB were examined by CE. Twelve of 24
      patients in the active bleeding group underwent laparoscopic or laparoscopy
      assisted surgery and we carried out intraoperative enteroscopy to find the focus
      of the bleeding. RESULTS: Laparoscopic localization of the lesion was successful
      for 4 patients-those with Meckel's diverticulum, gastrointestinal stromal tumor,
      lymphoma, and ischemic necrosis. In 3 cases in which there was no natural passage
      of the capsule endoscope, lesions were identified by small bowel exploration
      through simple palpation by hand. Intraoperative enteroscopy was performed
      extracorporeally in 5 cases through a minilaparotomy window using an extended
      incision of a port site less than 7 cm in length. The lesions that were
      identified by CE preoperatively were resected successfully, via laparoscopic or
      laparoscopy-assisted surgery. The gastrointestinal bleeding has not recurred
      during the postoperative follow-up period (mean, 10.6 months). CONCLUSION: The
      laparoscopic approach can be chosen for surgical management of OGB patients with
      active bleeding whose lesions have been identified by CE. This approach allows
      minimally invasive surgical treatment for ongoing OGB.

PMID- 16108739
TI  - Initial experience with laparoscopic bypass for upper gastrointestinal
      malignancy: a new option for palliation of patients with advanced upper
      gastrointestinal tumors.
AB  - BACKGROUND: The majority of patients with upper gastrointestinal (UGI) tract
      malignancy present at a stage where cure of disease is not possible. The aim of
      treatment in these patients is effective palliation. Various interventions have
      been described for the palliation of biliary and gastric outlet obstruction
      including open surgery, endoscopic and transparietal stent placement.
      Laparoscopic bypass appears to have the advantage of decreased postoperative pain
      and shorter hospital stay as well as offer effective palliation. The aim of this
      study was to assess the safety and efficacy of laparoscopic bypass in patients
      with incurable UGI tract malignancy. PATIENTS AND METHODS: Between August 2000
      and April 2002 laparoscopic gastric and biliary bypass concurrently or alone was
      attempted in 19 consecutive patients with unresectable carcinoma of the head of
      the pancreas, adenocarcinoma of the stomach, cholangiocarcinoma of the distal
      common bile duct, or adenocarcinoma of the duodenum. The operative time, length
      of postoperative stay, complications, and the effectiveness of the procedure in
      terms of the ability to sustain oral nutrition and or the relief of obstructive
      jaundice were recorded and used as outcome measures. RESULTS: Laparoscopic bypass
      was successful in 18 out of 19 cases. The mean operative time for a single bypass
      was 164 minutes while the average postoperative hospital stay was 11 days. All
      patients were able to sustain oral nutrition during the course of their hospital
      stay and or had effective relief from their obstructive jaundice. Two patients
      died from procedure unrelated causes within 30 days of the operation. CONCLUSION:
      Laparoscopic bypass appears to be a safe and effective means of palliation for
      patients with unresectable UGI tract tumors and should replace open surgical
      palliation in this group of patients.

PMID- 16108740
TI  - Laparoscopic cholecystectomy in the elderly: increased operative complications
      and conversions to laparotomy.
AB  - BACKGROUND: The incidence of gallstones increases with age and as the proportion
      of the population 65 years of age and older continues to grow, increased demand
      for laparoscopic cholecystectomy (LC) in the geriatric population is likely. LC
      has advantages over open cholecystectomy, but comparative evaluation of the
      procedure in elderly patients is lacking. METHODS: We performed a two-year review
      of patients undergoing LC at our institution. Demographic information, diagnosis,
      operation performed, and operative complications were recorded. Patients were
      placed into two groups by age: 65 years and older, and those younger than 65
      years of age. Primary outcome measures were complication rate and conversions to
      laparotomy. RESULTS: A total of 315 patients underwent LC during the study
      period, of whom 59 (19%) were 65 years of age or older. The older age group
      experienced higher rates of conversion to an open procedure (22% vs. 2.7%,
      P<0.05), and operative complications (17% vs. 3.1%, P<0.05). Elderly patients
      also had longer operative times (108+/-55 minutes vs. 83<34 minutes, P<0.05).
      Acute (31% vs. 16%) and chronic (14% vs. 7.4%) cholecystitis were the operative
      diagnoses in a greater proportion of patients in the older age group, and elderly
      patients were more likely to have had prior upper abdominal surgery (8.5% vs.
      1.6%, P<0.05). CONCLUSION: LC in the geriatric population carries increased risk
      for conversion to laparotomy and operative complications compared to LC in
      younger patients. This is likely due to increased acuity and chronic right upper
      quadrant inflammation in this population. Surgeons should bear these issues in
      mind in the counseling and care of these patients.

PMID- 16108741
TI  - Laparoscopic splenectomy for metastatic squamous cell cancer of the neck.
AB  - Squamous cell carcinoma (SCC) spreads through direct extension, lymphatic
      vessels, and, rarely, hematogenous routes. The most common malignancies to
      metastasize to the spleen include carcinomas of the breast, lung, and melanoma.
      We present an unusual case of SCC of the neck with splenic metastases. The
      patient presented with a primary solid tumor of the neck that extended into the
      surrounding soft tissues, including the internal jugular vein and regional lymph
      nodes. A metastatic work-up with a positron emission tomograph showed enhancement
      in the left upper quadrant. A computed tomograph (CT) was then performed. The CT
      revealed three distinct splenic lesions, the largest measuring 6x6.5x2.5 cm.
      Subsequently, the patient was scheduled for a splenectomy. At the time of
      operation, diagnostic laparoscopy revealed only the splenic lesions. A
      laparoscopic splenectomy was performed successfully and the patient was started
      on a regular diet on postoperative day 1. This paper describes the first
      documented case of SCC of the neck with splenic metastases. The lesion was
      diagnosed and treated laparoscopically. The case is described in detail along
      with the clinical implications of this rare finding.

PMID- 16108742
TI  - Gas embolism during laparoscopic cholecystectomy.
AB  - Advancements in laparoscopic surgery have resulted in decreased length of
      hospitalization, reduced postoperative pain, and better cosmesis following
      general surgical procedures. Carbon dioxide gas embolism is a rare occurrence
      that can be fatal. We report the case of a patient with a venous gas embolism
      during laparoscopic cholecystectomy. A 63-year-old woman presented with
      intermittent right upper quadrant pain, and her abdominal ultrasound showed a
      possible gallbladder polyp. A laparoscopic cholecystectomy was planned. A Veress
      needle was placed in the right upper quadrant to initiate abdominal access.
      Shortly after carbon dioxide insufflation, the patient's hemodynamic status
      deteriorated, her oxygen saturation dropped, and her end-tidal CO2 decreased. Gas
      insufflation was immediately stopped, and the patient was resuscitated. She
      stabilized quickly, and the procedure was performed without further event. She
      did well postoperatively and was discharged home the next day. Carbon dioxide
      embolism during laparoscopy, albeit rare, can be a fatal complication of the
      procedure. Whenever sudden changes in hemodynamic stability occur, venous gas
      embolism should be considered. As laparoscopic techniques and applications are
      expanded, the general surgeon must be aware of this entity.

PMID- 16108743
TI  - Laparoscopic Heller myotomy and Roux-en-Y gastric bypass: a novel operation for
      the obese patient with achalasia.
AB  - Morbid obesity is a disease encompassing multiple, significant comorbidities. The
      only current, reliable, durable treatment of obesity is surgical intervention,
      most commonly gastric bypass. Achalasia, a swallowing disorder of esophageal
      motility and failure of the lower esophageal sphincter (LES) to relax, is rarely
      seen in the morbidly obese patient. Treatment is directed at disruption of the
      LES to allow passage of food. As medical management usually fails in both disease
      processes, surgical treatment is often chosen. The patient with both morbid
      obesity and achalasia presents an unusual challenge for surgical treatment. The
      standard surgical approach for each disease does not address the other, and may
      have deleterious consequences on the other condition if approached unilaterally.
      We present the first case of a patient treated with a concomitant laparoscopic
      esophagogastric myotomy (LEM) and laparoscopic Roux-en-Y gastric bypass (LRYGBP).

PMID- 16108744
TI  - Laparoscopic-assisted small bowel resection of a leiomyoma causing recurrent
      obscure gastrointestinal bleeding.
AB  - A 62-year-old man experienced recurrent painless episodes of melenas and
      undiagnosed chronic anemia for 4 years. Despite extensive radiologic and
      endoscopic work-up, the origin of the bleeding could not be identified. At his
      last admission, visceral angiography revealed an area of hypervascularity at the
      initial portion of the jejunum, containing irregular, corkscrew vessels coming
      from the first jejunal branch of the superior mesenteric artery. Under general
      endotracheal anesthesia, a 10-mm trocar for the 30 degree laparoscope was
      inserted subumbilically using the open Hasson technique. Two 5-mm trocars were
      also used suprapubically and at the left iliac fossa. A 2.5 cm diameter, smooth,
      hypervascular tumor was easily visualized on the jejunal wall 10 cm from the
      ligament of Treitz. The small bowel segment was laparoscopically mobilized and
      brought through the subumbilical trocar site, which was extended 1 cm. A limited
      small bowel resection and a stapled anastomosis were easily performed
      extracorporeally. Histopathologic examination diagnosed a benign gastrointestinal
      tumor (gastrointestinal stromal tumor, leiomyoma). The patient was discharged on
      postoperative day 2. Laparoscopic identification and mobilization allows a loop
      of small bowel to be exteriorized through a small incision; the anastomosis can
      be safely performed extracorporeally. The advantages of rapid postoperative
      recovery and reduced pain are evident.

PMID- 16108745
TI  - Laparoscopic treatment of unicentric Castleman's disease with abdominal
      localization.
AB  - We report a case of unicentric Castleman's disease (angiofollicular lymph node
      hyperplasia) with abdominal localization, that was treated laparoscopically. The
      patient, a 23-year-old male, was referred to our unit for subtle symptoms of
      recurrent palpitations and vague abdominal pain. His physician had prescribed an
      abdominal echtomograph, which showed a mass located at the lower and anterior
      lower splenic pole. In order to reach a definite diagnosis and prescribe adequate
      treatment, a diagnostic laparoscopy was performed. Exploration of the abdominal
      cavity helped detect a well-vascularized solid round mass at the level of the
      left hypochondrium, with a vascular pedicle; the lesion was detached, and the
      pedicle sectioned using an Endo-GIA 40. The postoperative course was regular and
      the patient was discharged on postoperative day 2. The laparoscopic approach
      enabled the resection of the lesion (with consequent histological diagnosis) and
      exploration of the peritoneal cavity with the advantages of minimal invasiveness,
      magnified images, and more rapid recovery). The pathology was totally resolved,
      with satisfactory results in terms of recovery, postoperative pain, and cosmesis.

PMID- 16108746
TI  - Simultaneous laparoscopic adrenalectomy for pheochromocytoma and dismembered
      pyeloplasty for uretero-pelvic junction obstruction.
AB  - Laparoscopic adrenalectomy for pheochromocytoma and laparoscopic dismembered
      pyeloplasty are both technically difficult procedures. We describe the case of a
      61-year-old female patient who presented with a right adrenal pheochromocytoma
      and bilateral pelvi-ureteric junction obstruction with renal failure who
      underwent a successful simultaneous transperitoneal laparoscopic adrenalectomy
      and pyeloplasty.

PMID- 16108747
TI  - Colonoscopic removal of inguinal hernia mesh: report of a case and literature
      review.
AB  - The transabdominal preperitoneal (TAPP) procedure for laparoscopic inguinal
      hernia mesh repair is being applied with increasing frequency. This technique has
      an acceptable recurrence rate (0.4-3.9%), but has varying complication rates (1.3
      17.4%).1,2 We report the first case of mesh penetration of the colon following
      laparoscopic TAPP repair, treated with colonoscopy.

PMID- 16108748
TI  - Delayed presentation of ilio-iliac arteriovenous fistula following laparoscopic
      cholecystectomy treated with percutaneous graft-covered stent placement.
AB  - Major vascular injuries during laparoscopic cholecystectomy are rare, usually
      readily apparent, and immediately treated. We report a case of delayed
      presentation of a retroperitoneal vascular injury. The patient presented with
      abdominal pain and increasing edema of the lower extremities 1 year after
      laparoscopic cholecystectomy and was found to have an ilio-iliac arteriovenous
      fistula. Endovascular treatment was accomplished using a graft-covered
      polytetrafluoroethylene stent. The patient remained free of symptoms at 1-year
      follow-up.

PMID- 16108749
TI  - Analgesic efficacy of caudal block versus diclofenac suppository and local
      anesthetic infiltration following pediatric laparoscopy.
AB  - AIM: To compare the analgesic efficacy of caudal block with diclofenac
      suppository and local anesthetic infiltration in children undergoing laparoscopy.
      METHODS: We studied 50 children undergoing laparoscopy for diagnostic and
      therapeutic purposes. Their ages ranged from 3 to 13 years, and all belonged to
      American Society of Anesthesiologists (ASA) class I or II. Anesthesia was carried
      out using the standard procedure. Patients were randomly assigned to one of two
      groups. Group 1 received caudal block with bupivacaine 1 mL/kg after anesthetic
      induction. Group 2 received diclofenac suppository 3 mg/kg postinduction and
      local anesthetic infiltration at the port sites at the end of the procedure. Pain
      was assessed using the Hannallah objective pain scale at 15, 30, 60, 120, and 360
      minutes postextubation. RESULTS: The pain scores were comparable in both groups
      at all times. Twelve percent of caudal block patients and 20% of diclofenac
      patients needed rescue analgesic, a statistically insignificant difference. In 2
      patients, caudal block was technically difficult and they were excluded from the
      study. The incidence of side effects was low in our study. CONCLUSION: We find
      the analgesic efficacy of diclofenac suppository combined with local anesthetic
      infiltration at port sites comparable to caudal block. Given the necessarily
      invasive nature of caudal block, we suggest the combined use of diclofenac
      suppository with local anesthetic infiltration at port sites as a useful and more
      economical alternative for analgesia following pediatric laparoscopy.

PMID- 16108750
TI  - Twelve years of minimally invasive surgery in children and adolescents: a single
      center experience.
AB  - BACKGROUND/PURPOSE: Minimally invasive surgery plays an important role in the
      daily practice of pediatric surgeons. However, there have been few reports of
      large series of patients. The aim of this paper is to report our experience over
      the past 12 years with a broad range of pediatric laparoscopic procedures.
      METHODS: We performed a retrospective analysis of 1084 minimally invasive
      procedures conducted in the department of pediatric surgery from June 1992 to
      March 2004. RESULTS: The mean age of the patients was 14 years (range, 1-19).
      Seven hundred forty-six operations (69%) were thoracoscopic sympathectomy for
      hyperhydrosis. Other common operations were high ligation of spermatic vessels
      (n=98), cholecystectomy (n=65), exploration of nonpalpable testes (n=53),
      appendectomy (n=55), female adnexal surgery (n=24), and splenectomy (n=13).
      Thirty miscellaneous procedures included Nissen fundoplication, liver biopsies,
      diagnostic laparoscopy, Morgani and Bochdalek hernia repair, Swenson procedures,
      V-P shunt placement, splenic and hepatic cyst removal, thorcoscopy for pleural
      empyema, treatment of gastric ulcer perforation, and nephrectomy. We reviewed the
      indications for surgery, the surgical technique, and the outcome for each
      procedure. All patients in this series were well at follow-up and there was no
      long-term morbidity. CONCLUSION: Although laparoscopic procedures have gained an
      integral place in pediatric surgery and are relatively safe, advanced
      laparoscopic procedures should be developed, practiced and evaluated in dedicated
      surgical units to ensure a broad base of experience on which to base future
      decisions and guidelines.

PMID- 16108751
TI  - Tissue adhesives for repairing inguinal hernia: a preliminary study.
AB  - AIM: To investigate the efficacy of tissue adhesives for closing the orifice of
      the inguinal hernia sac (IHS) as an alternative method for treating inguinal
      hernia. METHODS: Five-week-old male Lewis rats (n=4) were used, because Lewis
      rats have a large patent IHS. The rats were divided into 9 groups (n=6 in each)
      according to the type of tissue adhesive used: G1, fibrin glue (Beriplast); G1b,
      Beriplast plus blood; G2, microfibrillar collagen hemostat (Avitene); G2b,
      Avitene plus blood; G3, fibrinogen-based sealant (TachoComb); G3b, TachoComb plus
      blood; G4, synthetic absorbable sealant (Advaseal); G5, bilateral single port
      laparoscopic injection of octylcyanoacrylate (Dermabond); and G6, sham operation
      (control group). In G1-G4, surgery was performed through a midline lower
      abdominal incision. In G5, a 5-mm laparoscope was inserted in the epigastrium, a
      fine catheter was passed through the side port of the laparoscope into the right
      HIS, and 0.2 mL Dermabond was injected. The left IHS was treated in the same way.
      All rats were sacrificed 3 months after treatment, and IHS patency was examined
      macroscopically. All rats in G5 and G6 were mated 50 days after treatment to
      check fertility. RESULTS: All rats survived until sacrifice. At sacrifice, all
      IHS were patent in G6. All IHS were also patent in G1-G4, but all IHS were closed
      at the internal ring in G5. In G5 there were no adhesions between the orifice of
      the closed sac and the small bowel in 5/6, and only minor adhesions in 1/6. G5
      fertility (5/6: 83%) was the same as for the control group (G6). CONCLUSION: Our
      results suggest that laparoscopic injection of Db into the IHS is simple, safe,
      reliable, virtually scarless, and may be a reasonable alternative to standard
      open surgical inguinal hernia repair.

PMID- 16108752
TI  - Laparoscopy in the management of antenatally detected liver masses.
AB  - Antenatally detected liver masses that are not clearly benign on postnatal
      investigation pose a management dilemma. Unless the diagnosis is clear,
      observation alone is risky. Improvements in radiological diagnosis permit
      confirmation of the benign nature of these masses in some instances, but it is
      usually difficult to distinguish them from malignant lesions. Since recent
      advances in ultrasound facilitate identification of liver masses during prenatal
      life, differential diagnosis of these masses has become a recurring issue in
      recent years. Laparoscopy may play a major role in the surgical management of
      right upper quadrant masses detected antenatally. We describe its use in a
      patient with an antenatally detected liver mass. No clear diagnosis could be made
      with radiologic investigation in the neonatal period. Definitive diagnosis was
      made laparoscopically: focal nodular hyperplasia was confirmed with laparoscopy
      and biopsy. In cases where the etiology of a liver mass remains unclear after
      radiologic investigation, laparoscopic intervention may prove beneficial in
      neonates and infants. We present an algorithm for the management of similar
      antenatally detected right upper quadrant lesions.

PMID- 16108753
TI  - Laparoscopic fenestration of a neonatally detected hepatic mesenchymal hamartoma.
AB  - We report a case of hepatic mesenchymal hamartoma that was detected neonatally
      and successfully treated by laparoscopic fenestration. A baby girl was referred
      to our hospital 9 days after birth with a cystic lesion in her liver. Screening
      abdominal ultrasonography revealed a sonolucent lesion measuring 65x43x40 mm in
      the right lobe of the liver with a small solid area. Magnetic resonance imaging
      depicted the lesion as hyperintense on both T1- and T2-weighted images with no
      enhancement. A laparoscopic biopsy and fenestration of the lesion was performed.
      Histologic examination of the cyst wall led to a diagnosis of hepatic mesenchymal
      hamartoma. The postoperative course was uneventful and the patient is doing well
      at 4 years' follow-up, with no recurrence.

PMID- 16108754
TI  - Total endoscopic vaginal reconstruction in a case of Mayer-Rokitansky-Kuster
      Hauser syndrome.
AB  - The congenital absence of the vagina is an uncommonly encountered malformation,
      known as Rokitanski- Kuster-Hauser syndrome. These patients may enjoy an improved
      quality of sexual life once a neovagina is constructed. Surgical and nonsurgical
      (Frank's autodilatation) methods of creating a neovagina by recurrent dilatations
      require long and often embarrassing self-catheterization which is often painful,
      and yield a vagina with limited length. The developing ability to perform
      complicated surgery by laparoscopy has revived interest in colonic and ileal
      interposition procedures for formation of a neovagina. We report a case of
      sigmoid colpoplasty for neovagina creation in a 15-year-old girl, performed
      completely by laparoscopy, with a favorable outcome and an easier recovery.

PMID- 16108757
TI  - Biochemical characterization of the chondroitinase ABC I active site.
AB  - cABC I (chondroitinase ABC I) from Proteus vulgaris is a GalAG
      (galactosaminoglycan) depolymerizing lyase that cleaves its substrates at the
      glycosidic bond via beta-elimination. cABC I cleaves a particularly broad range
      of GalAG substrates, including CS (chondroitin sulphate), DS (dermatan sulphate)
      and hyaluronic acid. We recently cloned and recombinantly expressed cABC I in
      Escherichia coli, and completed a preliminary biochemical characterization of the
      enzyme. In the present study, we have coupled site-directed mutagenesis of the
      recombinant cABC I with a structural model of the enzyme-substrate complex in
      order to investigate in detail the roles of active site amino acids in the
      catalytic action of the enzyme. The putative catalytic residues His-501, Tyr-508,
      Arg-560 and Glu-653 were probed systematically via mutagenesis. Assessment of
      these mutants in kinetic and end-point assays provided direct evidence on the
      catalytic roles of these active-site residues. The crystal structure of the
      native enzyme provided a framework for molecular docking of representative CS and
      DS substrates. This enabled us to construct recombinant enzyme-substrate
      structural complexes. These studies together provided structural insights into
      the effects of the mutations on the catalytic mechanism of cABC I and the
      differences in its processing of CS and DS substrates. All His-501 mutants were
      essentially inactive and thereby implicating this amino acid to play the critical
      role of proton abstraction during catalysis. The kinetic data for Glu-653 mutants
      indicated that it is involved in a hydrogen bonding network in the active site.
      The proximity of Tyr-508 to the glycosidic oxygen of the substrate at the site of
      cleavage suggested its potential role in protonating the leaving group. Arg-560
      was proximal to the uronic acid C-5 proton, suggesting its possible role in the
      stabilization of the carbanion intermediate formed during catalysis.

PMID- 16108758
TI  - Amantadine in treatment of chronic hepatitis C virus infection?
AB  - SUMMARY: Treatment of chronic hepatitis C (CHC) continues to be an important and
      growing challenge. As the response rate to FDA-approved treatment improved over
      the past decade, we are facing increasing number of difficult-to-treat patients
      such as those who have failed prior anti-viral therapy. The role of amantadine in
      the treatment of CHC remains unclear. Studies thus far have produced conflicting
      results, and type II error could not be excluded. This review summarized results
      published in the literature from 1997 to 2003, and reviewed the existing
      questions and controversies regarding the use of amantadine. Current literature
      suggests that amantadine is ineffective as monotherapy. Amantadine increased the
      sustained virologic response of certain treatment naive patients when used in
      combination with interferon, and may be effective as an adjunct to interferon
      based combination therapy in some patients who have failed or relapsed on prior
      therapy. Factors such as small sample size, patient characteristics, and
      differences in treatment protocols including amantadine preparation and duration
      of therapy might explain the conflicting observations of various studies. Further
      investigations are needed to define optimal dosing and formulation of amantadine,
      and its appropriate role in management of CHC infection.

PMID- 16108759
TI  - Relationship of genotypes of hepatitis B virus to mutations, disease progression
      and response to antiviral therapy.
AB  - SUMMARY: Phylogenetic analysis has led to the classification of hepatitis B virus
      into eight genotypes, designated A to H. The genotypes have differences in
      biological properties and show heterogeneity in their global distribution. These
      attributes of the genotypes may account not only for differences in the
      prevalence of hepatitis B virus mutants in various geographic regions, but also
      be responsible for differences in the clinical outcome and response to antiviral
      treatment in different population groups.

PMID- 16108756
TI  - Biochemical dysfunction in heart mitochondria exposed to ischaemia and
      reperfusion.
AB  - Heart tissue is remarkably sensitive to oxygen deprivation. Although heart cells,
      like those of most tissues, rapidly adapt to anoxic conditions, relatively short
      periods of ischaemia and subsequent reperfusion lead to extensive tissue death
      during cardiac infarction. Heart tissue is not readily regenerated, and permanent
      heart damage is the result. Although mitochondria maintain normal heart function
      by providing virtually all of the heart's ATP, they are also implicated in the
      development of ischaemic damage. While mitochondria do provide some mechanisms
      that protect against ischaemic damage (such as an endogenous inhibitor of the
      F1Fo-ATPase and antioxidant enzymes), they also possess a range of elements that
      exacerbate it, including ROS (reactive oxygen species) generators, the
      mitochondrial permeability transition pore, and their ability to release
      apoptotic factors. This review considers the process of ischaemic damage from a
      mitochondrial viewpoint. It considers ischaemic changes in the inner membrane
      complexes I-V, and how this might affect formation of ROS and high-energy
      phosphate production/degradation. We discuss the contribution of various
      mitochondrial cation channels to ionic imbalances which seem to be a major cause
      of reperfusion injury. The different roles of the H+, Ca2+ and the various K+
      channel transporters are considered, particularly the K+(ATP) (ATP-dependent K+)
      channels. A possible role for the mitochondrial permeability transition pore in
      ischaemic damage is assessed. Finally, we summarize the metabolic and
      pharmacological interventions that have been used to alleviate the effects of
      ischaemic injury, highlighting the value of these or related interventions in
      possible therapeutics.

PMID- 16108760
TI  - Clinical utility of viral load measurements in individuals with chronic hepatitis
      C infection on antiviral therapy.
AB  - SUMMARY: Both absolute viral load and log decline in viral load from baseline
      were found clinically useful in predicting sustained virological response and
      lack of sustained virological response (non-sustained virological response, NSVR)
      to treatment. We assessed the clinical utility of hepatitis C virus (HCV) RNA
      quantitation and changes in viral load using the VERSANT HCV RNA 3.0 Assay (bDNA)
      in 351 HCV-infected individuals treated with interferon plus ribavirin. We show
      that viral load decision thresholds provided negative predictive values (NPVs) of
      >95% at week 4 using a 100 000 IU/mL cut-off and at weeks 8 and 12 using 10 000
      IU/mL cut-offs. A 2-log decline from baseline provided NPVs >95% at weeks 8 and
      12. Combinations of absolute viral loads and changes in viral load from baseline
      did not enhance the performance of the decision rules for predicting NSVR. The
      positive predictive values (PPVs) at weeks 8 and 12 were 59.1 and 67.3%. This
      study highlights the critical importance of viral quantitation in gauging
      therapeutic response in patients with chronic HCV infection on antiviral therapy.
      Early changes in viral load, measured as absolute viral loads or change in viral
      load from baseline, are highly predictive of NSVR at 8 and 12 weeks. PPVs are
      modest but these data may provide encouragement to patients who are in the early
      phases of treatment when side effects are frequent. Additionally, we demonstrated
      the need for cautious interpretation of stopping rules when the values are at or
      near the decision thresholds.

PMID- 16108761
TI  - Hepatitis C virus RNA kinetics during the initial 12 weeks treatment with
      pegylated interferon-alpha 2a and ribavirin according to virological response.
AB  - SUMMARY: To optimize treatment of chronic hepatitis C early identification of
      patients who will not achieve a sustained virological response (SVR) is
      desirable. We investigated hepatitis C virus (HCV) RNA kinetics at day 1 (in 15
      patients; genotypes 1 and non-1, 9 and 6 respectively) at weeks 1, 4 and 12 (in
      53 patients; genotypes 1 and non-1, 19 and 34, respectively) during treatment
      with pegylated interferon alpha-2a and ribavirin. Patients with SVR had a
      significantly more pronounced mean log10 decline from baseline in HCV RNA levels
      at weeks 1 and 4 compared with patients who failed to achieve SVR (1.99 vs 0.85
      at week 1, P = 0.0003 and 2.89 vs 1.72 at week 4, P = 0.0159), whereas no
      difference was noted after day 1. For patients with a 2-log10 decrease in HCV RNA
      levels at day 7, the positive predictive value (PPV) for a SVR was 92%, whereas
      week 12 was the best time point for predicting a later nonresponse [negative
      predictive value (NPV) 92%] in patients failing to achieve a 2-log10 drop. For
      patients with genotype non-1 and a 2-log10 decrease in HCV RNA levels the PPV for
      a SVR was 89% week 1, and 79% weeks 4 and 12. The corresponding NPV for patients
      with genotype non-1 were 43, 40 and 100% respectively. During treatment with
      pegylated interferon alpha-2a plus ribavirin the HCV RNA decline at week 1 was an
      accurate predictor of SVR in patients who had achieved a 2-log10 drop in HCV RNA
      levels, whereas the lack of such decline week 12 was an accurate marker of a
      nonresponse.

PMID- 16108762
TI  - Clinical usefulness of total hepatitis C virus core antigen quantification to
      monitor the response to treatment with peginterferon alpha-2a plus ribavirin*.
AB  - SUMMARY: Early virological response may predict outcome following treatment with
      peginterferon alpha-2a and ribavirin in patients chronically infected with
      hepatitis C virus (HCV). As total HCV core antigen may constitute an alternative
      direct marker to HCV RNA for assessing the levels of viraemia in such patients,
      we evaluated the correlation between HCV core antigen and HCV RNA, and whether
      HCV core antigen at baseline, 4 and 12 weeks after treatment could predict
      sustained virological response (SVR) to combined therapy, in comparison with HCV
      RNA. A total of 290 serum samples from 58 previously treatment naive chronic HCV
      patients were examined for HCV core antigen and HCV-RNA by means of quantitative
      HCV RNA when receiving combination therapy for the first time. SVR was
      significantly associated with basal HCV core antigen but not with HCV RNA. There
      was a good correlation between HCV core antigen and HCV RNA (r(2) = 0.781). The
      negative predictive value of HCV core antigen testing in predicting nonresponse
      at weeks 4 and 12 were 75 and 100%, and for undetectable or a 2-log drop in HCV
      RNA were 69.6 and 75% respectively. HCV core antigen detection is quick, and easy
      to perform alternative to HCV RNA, and could be used as a marker of HCV viraemia
      for monitoring the progress of therapy.

PMID- 16108763
TI  - Telomerase reverse transcriptase mRNA expression in peripheral lymphocytes of
      patients with chronic HBV and HCV infections.
AB  - SUMMARY: Telomerase activity is present at low levels in peripheral lymphocytes
      (PL) and is upregulated upon activation, possibly protecting PL from telomere
      shortening. As decreased telomere length is considered a sign of cellular
      senescence, telomerase may, therefore, play an important role on immune function,
      organ regeneration and carcinogenesis. So far, quantification of human telomerase
      reverse transcriptase levels (hTERT) in PL, has not been reported. We determined
      hTERT mRNA levels in PL of hepatitis B virus (HBV) and hepatitis C virus (HCV)
      patients, in an attempt to address whether hTERT transcripts in PL are altered in
      these viral diseases, which are characterized by immune dysfunction and increased
      incidence of hepatocarcinogenesis. hTERT mRNA levels in PL of HBV (n = 17), HCV
      (n = 24) patients and healthy controls (n = 22) were quantified by real-time
      polymerase chain reaction. We observed significantly lower hTERT mRNA levels in
      HBV and HCV patients compared with healthy individuals (P < 0.05). hTERT mRNA
      levels were not associated with the patients' clinical status (inactive,
      hepatitis and cirrhosis). Also no correlation was observed between hTERT mRNA
      expression, and HBV and HCV replicative activity. In the inactive group (n = 18)
      we observed a negative correlation between hTERT mRNA expression and disease
      duration (rs = -0.52, P < 0.03). We performed for the first time an accurate
      quantification of hTERT mRNA expression in PL of HBV and HCV patients. The
      observed low levels of hTERT mRNA expression in the above patients may suggest
      its involvement in the immunopathogenesis of chronic viral hepatitis.

PMID- 16108764
TI  - Interferon reduces somatic mutation of mitochondrial DNA in liver tissues from
      chronic viral hepatitis patients.
AB  - SUMMARY: We recently reported that the genetic instability resulting in the high
      rate of mitochondrial DNA (mtDNA) mutation in noncancerous liver tissue is
      consistent with the multicentric hepatocarcinogenesis detected clinically.
      Interferon (IFN) has been reported to reduce hepatocarcinogenesis in individuals
      with hepatitis virus infection. Liver biopsy specimens were obtained from 26
      patients with chronic hepatitis C virus (HCV) infection before and after IFN
      therapy (total dose: 252 million units). The mean (+/-SD) age of the study
      population was 45 +/- 9 years and 13 (50%) were male [mode of acquisition: blood
      transfusion (27%), unknown (73%); viral load: 5.2 +/- 1.1 k copies/mL; duration
      of infection: 17 +/- 9 years (65%), unknown (35%); genotype: I (4%), II (80%),
      III (8%), IV (8%); alcohol intake: positive (31%), negative (69%)]. DNA samples
      were extracted from the specimens and subjected to direct sequencing. The mtDNA
      mutation frequency in the D-loop was increased in liver specimens from
      individuals with HCV infection compared with 21 controls (2.5 vs 0.6, P < 0.001).
      IFN therapy decreased the mtDNA mutation (mean difference = 0.7, P < 0.001) and
      the decreased number of mtDNA mutations was positively correlated with
      suppression of the total histological activity index score (mean difference =
      1.3, P < 0.01). These results clearly indicate that the mutational rate of mtDNA
      is strongly associated with IFN therapy. Thus, analysis of mtDNA could provide a
      new criterion for the therapeutic evaluation of the effect of IFN, and may be
      useful for the prediction of risk of carcinogenesis.

PMID- 16108765
TI  - Interferon-alpha suppresses liver cell proliferation in patients with chronic
      hepatitis C virus infection.
AB  - SUMMARY: Interferon (IFN) therapy has been shown to reduce the risk of
      hepatocellular carcinoma (HCC) in patients with chronic hepatitis C, including
      virological nonresponders (NR). Whether IFN suppresses liver cell proliferation,
      i.e. the relevant risk factor for HCC, is unknown. The aim of the study was to
      evaluate the effect of IFN therapy on liver cell proliferation in chronic
      hepatitis C. The proliferating cell nuclear antigen-labelling index (PCNA-LI) was
      assessed prior to and at the end of therapy in the liver of 29 patients with
      chronic hepatitis C who received 3 MU IFN-alpha2b thrice weekly for 24-48 weeks.
      Overall, the median value of PCNA-LI was significantly reduced from 2.6% to 1.1%
      at the end of therapy (P < 0.0001). At baseline, PCNA-LI median values were
      similar in the 15 virological responders compared with the 14 NRs (2.3%vs 3.4%, P
      = 0.121) and at the end of therapy, median changes of PCNA-LI (-1.4%vs-1.1%, P =
      0.089) were also similar although there was a higher decline of the proliferation
      index in responders with respect to NRs at the end of therapy (0.7%vs 1.6%, P =
      0.004). In the two groups, the rate of fibrosis score reduction was also similar
      (7%vs 20%, P = 0.326). In contrast, the histological activity index was more
      often reduced in responders than in NRs both at the >or=2 and >or=4 points
      reduction level (80%vs 36%, P = 0.02 and 53%vs 14%, P = 0.03, respectively). The
      study showed a significant suppression of liver cell proliferation in IFN-treated
      patients with chronic hepatitis C. Although the strongest IFN effect was observed
      in virological responders, a reduction of proliferative activity was also seen in
      virological NRs.

PMID- 16108766
TI  - Flow cytometry of fine-needle-aspiration biopsies: a new method to monitor the
      intrahepatic immunological environment in chronic viral hepatitis.
AB  - SUMMARY: Information about the character and grade of the intrahepatic immune
      response in viral hepatitis is important for the evaluation of disease stage and
      effect of therapy. Complications like haemorrhage limit the frequent performance
      of tissue-needle biopsies (TB), and the cells of peripheral blood have to be used
      as surrogate markers instead. Fine-needle-aspiration biopsy (FNAB) of the liver
      represents a safe and atraumatic method that allows frequent cytological
      sampling. Our aim was to investigate whether flow cytometry of FNAB specimens
      allows co-analysis of phenotype, function and specificity of key populations of
      liver-infiltrating lymphocytes (LIL). In 20 consecutive patients with chronic
      viral hepatitis [10 hepatitis B virus (HBV), 10 hepatitis C virus (HCV)], flow
      cytometry was performed on FNAB cytology, and simultaneously on lymphocytes
      isolated from a TB and peripheral blood mononuclear cells (PBMC). The ratio of
      CD8+/CD4+ lymphocytes in FNAB correlated well with LIL from TB (r =0.78, P <
      0.05) but differed from PBMC (mean ratio: 2.6, 2.1 and 0.7, respectively).
      Similarly, a correlation was observed for percentage CD56+ natural killer (NK)
      cells (mean %: 29.9, 32.3 and 14.5, respectively; r = 0.69, P < 0.05). The
      percentage of interferon (IFN)-gamma-producing CD3+ lymphocytes in both FNAB and
      TB was higher than in PBMC (mean %: 41, 44 and 22, respectively; P < 0.05).
      Furthermore, tetrameric complexes allowed analysis of HBV-specific T cells in
      FNAB specimens. In conclusion, flow cytometry of FNAB allows easy, atraumatic and
      reliable analysis of lymphocytes obtained from the intrahepatic compartment.
      Therefore, the FNAB is a valuable tool in the study of the immunopathology of
      viral hepatitis, and it may contribute to the improved clinical evaluation of
      chronic viral liver disease.

PMID- 16108767
TI  - Hepatic necroinflammation and fibrosis in patients with genotypes Ba and C, core
      promoter and precore mutations.
AB  - SUMMARY: The role of infection with hepatitis B virus (HBV) genotypes on liver
      histology is largely unknown. The aim of study was to investigate the
      relationships between HBV genotypes (B, C), core-promoter (CP) and precore
      mutants and liver histology in 66 patients. Liver biopsies were scored by
      histologic activity index (HAI). HBV genotypes were determined by enzyme-linked
      immunosorbent assay (ELISA). Eighteen (27.3%) and 48 patients (72.7%) had
      genotype B (all were subtype Ba) and C, respectively. Forty-seven (71.2%) and 27
      (40.9%) had CP and precore mutations, respectively. Patients with genotype C
      compared with subtype Ba had higher median scores of HAI-necroinflammation (HAI
      NI) (7 vs 3), HAI-fibrosis (HAI-F) (1 vs 0) and total HAI (8.5 vs 3) (all P <
      0.03). Patients with CP mutations compared with wild-type had higher median
      scores of HAI-NI (7 vs 3), HAI-F (3 vs 0) and total HAI (9 vs 3) (all P < 0.03).
      Forty patients (83.5%) with genotype C had CP mutations. Age and alanine
      aminotransferase levels were positively correlated with HAI scores while albumin
      levels were negatively correlated (P < 0.01 for all, except albumin levels and
      HAI-F, P = 0.08). There was no association between precore mutations and HAI
      scores. Multivariate analysis indicated that higher alanine aminotransferase
      (ALT) levels were associated with higher HAI scores (P < 0.04) and CP mutations
      were associated with higher HAI-NI (P = 0.034), but not with HAI-F score (P =
      0.3). CP mutations were associated with more severe necroinflammation. The
      association between genotype C and poor histology was probably because of the
      association between genotype C and CP mutations.

PMID- 16108768
TI  - Polymorphisms of the renin-angiotensin system and the severity of fibrosis in
      chronic hepatitis C virus infection.
AB  - SUMMARY: Patients with chronic hepatitis C virus (HCV) infection vary in their
      rates of fibrosis progression. The renin-angiotensin system (RAS) regulates
      fibrosis. Polymorphisms in the genes of the RAS may contribute to the outcome of
      renal and cardiovascular disease. We studied four RAS gene polymorphisms in 195
      patients with chronic HCV infection. Patients were grouped by Ishak stage of
      fibrosis on liver biopsy: group 1 (fibrosis score 0 or 1; n = 97), group 2
      (fibrosis score 2 or 3; n = 73) and group 3 (fibrosis score 4-6; n = 25).
      Polymorphisms of the angiotensinogen (AGT) gene (M235T and AT-6), the angiotensin
      I converting enzyme gene and the type 1 angiotensin II receptor gene were
      assayed. There was no difference in the distribution of these polymorphisms of
      the RAS between the fibrosis groups. There did not appear to be any increased
      prevalence of fibrosis if two or even three of the polymorphisms associated with
      increased RAS effect were present. On multivariate analysis factors significantly
      associated with fibrosis were necroinflammatory activity (P < 0.001) and age (P <
      0.001). No association was identified between these four RAS polymorphisms and
      fibrosis in chronic HCV infection.

PMID- 16108769
TI  - Cytokine profile of peripheral blood mononuclear cells from patients with
      different outcomes of hepatitis C virus infection.
AB  - SUMMARY: The relationship between the balance of helper T-cell type 1 (Th1) or
      type 2 (Th2) cytokines and the clinical course of hepatitis C virus (HCV)
      infection is unclear. We evaluated Th1 [interleukin (IL)-2, interferon-gamma (IFN
      gamma)] and Th2 cytokine (IL-4, IL-10) and 2,5-oligoadenylate synthetase (OAS, an
      IFN-induced antiviral protein) production by peripheral blood mononuclear cells
      from 10 healthy anti-HCV-positive individuals (group A), 10 HCV-RNA-positive with
      persistently normal alanine aminotransferase (ALT) levels (group B), 10 HCV-RNA
      positive with abnormal ALT (group C) and 10 uninfected healthy controls. IL-2
      production was significantly increased in group B when compared with all the
      other groups. No difference was found for IFN-gamma. IL-4 was significantly
      higher in group C than in both group B (P = 0.0006) and controls (P = 0.004).
      Compared with controls, IL-10 was significantly decreased in group A (P = 0.013)
      and B (P = 0.004). The production of 2,5-OAS was significantly higher in group B
      than in A (P = 0.04) and in C (P = 0.004). Finally, in all HCV-RNA-positive
      patients, a significant correlation was found between ALT and both IL-2 (r = 
      0.78; P = 0.0008) and IL-4 (r = 0.75; P = 0.0008). IN CONCLUSION: (i) subjects
      who cleared HCV showed a cytokine profile similar to controls; (ii) a
      preferential shift towards a Th1 profile seems associated with a more favourable
      clinical outcome in chronic hepatitis C; and (iii) a prevalent Th2 profile seems
      implicated in HCV pathogenesis and severity of liver disease.

PMID- 16108770
TI  - Weight loss during pegylated interferon and ribavirin treatment of chronic
      hepatitis C*.
AB  - SUMMARY: Treatment of hepatitis C virus (HCV) infection with interferon (IFN)
      alpha, as monotherapy or in combination with ribavirin, is associated with
      significant side-effects including weight loss. The aim of our study was to
      describe the evolution of body weight during combination antiviral treatment and
      to examine the possible determinants of weight loss. This was a retrospective
      analysis of 126 patients who received combination therapy of pegylated IFN-alpha
      2b and ribavirin at our unit. Body weight was recorded at each outpatient
      attendance during treatment and follow-up, and was expressed as a percentage of
      baseline value. We observed a decline of body weight during treatment. Median
      (range) weight values at 4, 12, 24, and 48 weeks (expressed as percentage of
      baseline weight) were 97.7 (91.5-110.2), 95.4 (84.4-109.4), 93.7 (80.8-106.5),
      and 91.1 (80.1-103.6) respectively. There was no significant association of
      increased weight loss with age, gender, pretreatment weight, ethnicity,
      pretreatment histological stage, cumulative IFN dose (adjusted for body weight),
      HCV genotype or treatment outcome. Median body weight returned to baseline within
      6 months of stopping treatment. Patients experience significant weight loss
      during combination therapy. Those experiencing greater weight losses during
      therapy did not benefit from improved antiviral response.

PMID- 16108771
TI  - Higher doses of peginterferon alpha-2b administered twice weekly improve
      sustained virological response in difficult-to-treat patients with chronic
      hepatitis C: results of a pilot randomized study.
AB  - SUMMARY: Beside substantial progress in treatment of chronic hepatitis C (CHC)
      particular patients (genotype 1/4, high viral load, previous nonresponse,
      cirrhosis) remain difficult to treat. The aim of our pilot randomized study was
      to compare efficacy and tolerability of standard doses of Peginterferon alpha-2b
      + ribavirin with higher doses of Peginterferon alpha-2b administered twice weekly
      + ribavirin. Sixty-five outpatients with CHC were subsequently enrolled. Group A
      (n = 22) received recommended doses of Peginterferon alpha-2b and group B (n =
      43), received high doses twice weekly. Groups were comparable for baseline
      characteristics. All genotype 1/4 patients had high baseline viraemia. Sustained
      virological response (SVR) was significantly higher in group B among naive
      patients (72%vs 25%, P = 0.024). A significantly higher rate of SVR was observed
      in group B both considering only genotype 1/4 patients, (46%vs 13%, P = 0.03) and
      grouping together genotype 1/4 naive and relapsers (57%vs 11%, P = 0.039).
      Discontinuation rate was 32% (7 of 22) in group A and 21% (9 [corrected] of 43)
      in group B. Our response rates are the highest reported for genotype 1/4 with
      high viraemia. Our pilot study supports the need of randomized studies to
      evaluate both viral kinetics and efficacy of high dose and twice weekly
      administration of Peginterferon alpha-2b in genotype 1/4 patients with high
      viraemia who may need personalized treatment schedules.

PMID- 16108772
TI  - Future trends of HCV-related cirrhosis and hepatocellular carcinoma under the
      currently available treatments.
AB  - SUMMARY: The epidemic of hepatitis C virus (HCV) infection is a major public
      health issue. We conducted a comprehensive analysis to estimate future HCV
      related morbidity and mortality, using a model which is the first to take into
      account currently available treatments. We reconstructed the incident infections
      per year in the past that progressed to chronic hepatitis C (CHC) in Greece.
      Then, the natural history of the disease was simulated in subcohorts of newly
      infected subjects in the presence or absence of treatment using yearly estimates
      of the number of treated patients obtained from national databases. Annual
      estimates of the incidence and prevalence of CHC by fibrosis stage,
      hepatocellular carcinoma (HCC) and mortality were obtained up to 2030. The
      current proportion of naive CHC patients receiving treatment in Greece is 1.2%
      per year. Treatment of 1.2-10% of naive CHC patients per year would reduce the
      cumulative number of incident cirrhosis and HCC cases from 2002 to 2030 by 10.8
      39.4% and 12.8-39.8%, respectively and decrease the number of prevalent cirrhosis
      and HCC cases in 2030 by approximately 17-48% compared with the number estimated
      under the assumption of no treatment. Approximately 17 cirrhosis cases or six HCC
      cases or 10 premature deaths would be prevented for every 100 treated patients.
      However, the prevalent cirrhotic/HCC cases because of HCV and HCV-related deaths
      would not plateau until 2030. Despite the introduction of effective treatment,
      HCV-related morbidity and mortality will likely increase during the next 20-30
      years in Greece. Intensive primary prevention efforts coupled with increased
      access to the currently available treatments are necessary to control the chronic
      consequences of HCV epidemic.

PMID- 16108773
TI  - Changes in epidemiological patterns of HCV infection and their impact on liver
      disease over the last 20 years in Greece.
AB  - SUMMARY: The aim of this study was to investigate the relative frequency of
      hepatitis C virus (HCV) genotypes in Greek patients with chronic infection as
      well as possible secular changes in their distribution in relation to modes of
      transmission, age and time at acquisition of the infection and other variables.
      We evaluated 434 unselected patients, 241 males and 193 females with a median age
      of 46.2 years (18-75), with chronic HCV infection presenting during the period
      1996-2000. HCV infection was confirmed by the detection of HCV-RNA by polymerase
      chain reaction (PCR), while HCV genotyping was performed by the Inno-LiPA assay.
      Liver biopsies were evaluated according to Ishak's scoring system. Of 434
      patients, 167 had a history of blood transfusion [post-transfusion hepatitis
      (PTH)], 80 were i.v. drug users and in 187 the route of infection remained
      unknown. The overall distribution of HCV genotypes 1, 2, 3 and 4 was 47, 8.3, 27
      and 15.2%, respectively. Genotype 3 was common in younger adults and i.v. drug
      users, whereas genotype 1 predominated in older people and PTH patients (P <
      0.001 for both). Infection acquired before 1981 (group A) was related to
      transfusion and genotype 1, while after 1981 (group B) with i.v. drug use and
      genotype 3 (P < 0.01). Biopsy was available in 369 (85%) patients, of whom 22.5%
      had cirrhosis; 29.8% in group A and 9.9% in group B. In a multivariate analysis,
      cirrhosis was strongly associated with the duration of infection (P = 0.013). Our
      study revealed a change of HCV genotype distribution in the last 20 years among
      Greek patients with chronic HCV infection as a result of epidemiological changes
      in HCV transmission. The presence of cirrhosis was associated only with the
      duration of infection. These observations have impact both on prevention and
      treatment.

PMID- 16108774
TI  - Health economics and nursing management.

PMID- 16108775
TI  - Alternative futures for health economics: implications for nursing management.
AB  - As nursing has been subject to successive waves of 'managerialism' there has been
      a drive on the part of government and elements within the profession to enhance
      the science base and promote cost-effective health care interventions. This has
      generated new interest in the 'economics of nursing' as efficiency and 'value for
      money' are viewed as necessary precondition for the provision of a high quality
      nursing service. As an academic subject health economics has brought an elegant
      set of theories to bear on the topic of health and health care. However,
      mainstream health economics is premised on a series of simplifying assumptions
      that, if applied uncritically, can induce a range of unintended and adverse
      consequences. This paper asks how ideas developed in one sphere (health
      economics) can be become influential in another (nursing management and practice)
      and it seeks explanations in the theories of Michel Foucault, specifically in his
      exploration of the reciprocal relationship between power and knowledge. How are
      our assumptions about what is possible and desirable shaped, how far do
      mechanisms of surveillance and self-subjugation extend? A range of alternative
      economic approaches have been developed which challenge many mainstream health
      economics assumptions. Some of these are better suited to the complex social
      environment present within health care. Nurses, nurse managers and researchers
      should question the assumptions of dominant economic models and explore a range
      of economic frameworks when planning services and evaluating their practice.

PMID- 16108776
TI  - Nursing agency and governance: registered nurses' perceptions.
AB  - AIM: To explore registered nurses' perceptions of standards of nursing practice
      and factors that affect nursing practice standards. BACKGROUND: Nursing
      governance affects nurses' ability to manage nursing practice standards. Lack of
      nursing professional autonomy has been associated with occupational
      dissatisfaction, stress, turnover and low morale, which impact upon care quality.
      METHOD: Grounded theory was used. Data, gathered by semistructured interviews
      with 142 nurses, theoretically sampled from three National Health Service
      hospitals were analysed using constant comparative analysis. FINDINGS: Nurses
      were dissatisfied with their governance over factors that they believed had most
      influence on nursing practice standards. Perceived lack of control over factors
      that affect practice standards generated dissatisfaction, frustration and
      demoralization. CONCLUSIONS: Nurses' perceived lack of governance over their
      practice requires investigation and attention if occupational dissatisfaction,
      stress, turnover and low morale, which impact on quality care, are to be reduced.
      Dissatisfaction with nursing governance indicates a need to review nurses'
      professional involvement in clinical governance.

PMID- 16108777
TI  - Thinking about equity in health care.
AB  - Public health care systems such as the British National Health Service typically
      profess two principal objectives: to improve the health of the whole population;
      and to reduce inequalities in health within it. Given scarce resources, these
      objectives are often in conflict. Much attention has justifiably been paid, by
      health economists, to addressing the former objective with methods of economic
      appraisal. My intention is to focus on the more difficult issue of the pursuit of
      'equity' in health care, specifically the desire to reduce inequalities in
      health. This raises philosophical and policy questions about what makes some
      people more deserving of care than others, and whether or not society should
      adopt a forgiving stance towards those who have compromised their health status
      in some way, and offer access to treatment. Also, decision-makers may need to
      distinguish between the goal of raising the level of those worse-off and reducing
      inequality across society as a whole. Moreover, it is important to clarify what
      we wish to be made less unequal within the realm of health care provision. Tough
      decisions like these are based on value judgements and trading off one priority
      against another. In the interests of equity, such decisions need to be
      transparent and based on the preferences of society as a whole rather than covert
      and capricious. No manager needs reminding that resources are limited or that if
      more favourable treatment is accorded to some, inevitably less favourable
      treatment is accorded to others. Policy-making for a whole unit requires a nurse
      manager to offer a perspective on multidisciplinary matters and engage in wider
      public policy issues facing the team. As circumstances change, existing practice
      may be challenged as unfair, inefficient, or failing to account for important
      patient characteristics which make them different. Here, thinking clearly about
      equity is very important, and nurse managers are important as clarifiers of the
      thinking about what should be considered when making these difficult decisions.

PMID- 16108778
TI  - Competition in health care: what does it mean for nurse managers?
AB  - The English Government has launched a series of radical market-orientated reforms
      whose goal is to get the National Health Service to 'act smarter' by undermining
      with public-private competition the monopoly power of providers, in particular
      'inflexible' National Health Service hospitals and medical practitioners. The
      failure of nurses and managers to remedy well established problems in the
      delivery of health care, for instance variations in medical practice, medical
      errors and the continued absence of measures of patient outcome or clinical
      success, together with slow changes in waiting time performance, has persuaded Mr
      Blair to use the market to induce more rapid change. Whether this unevaluated and
      radical social experiment will succeed is impossible to forecast precisely.
      However, it will oblige nurse managers to have increased recourse to the evidence
      base and the need to translate such material in improved practice. It will also
      oblige them to be able to access and use in their day-to-day management improved
      administrative data about practice activity and patient outcomes.

PMID- 16108779
TI  - Benchmarking occupational stressors and strain levels for rural nurses and other
      health sector workers.
AB  - This study was conducted with 1097 employees (866 females, 217 males, 14 did not
      indicate gender) in a regional Health Service District who completed the
      Queensland Public Agency Staff Survey in 2002. Nurses' results on measures of
      organizational climate and psychological outcomes were compared with those of
      other employees in the Health Service District. Nurses reported less favourable
      outcomes on all but one of the organizational climate scales, and also were found
      to have more distress (strain), and lower levels of morale, Job Satisfaction and
      Quality of Worklife than others. Results were generally less favourable for
      nurses working in the large regional hospital and in mental health than for
      nurses in other facilities. The study has implications for recruiting and
      retaining nurses at a time when shortages within the profession are chronic.

PMID- 16108780
TI  - Economic evaluation: what does a nurse manager need to know?
AB  - This paper considers how health economists can assist nurse managers, using the
      concepts and tools of economic evaluation. We aim to clarify these and also
      explode some of the myths about economic evaluation and its role in health care
      decision-making. Economic evaluation techniques compare alternative courses of
      action in terms of their costs and consequences. There are four principal
      methods; cost-minimization, cost-effectiveness, cost-utility and cost-benefit
      analysis, all of which synthesize costs and outcomes, at different levels of
      outcome. Economic evaluation is an intrinsic part of national decision-making
      about the efficient provision of effective treatments and services, and
      increasingly, organizational matters. In the UK, such technology evaluation is
      disseminated in guidelines from the National Institute for Clinical Effectiveness
      (NICE), having a top-down impact on the nurse manager. But economic evaluation is
      increasingly relevant to the nurse manager at local level, through newer
      techniques such as Programme Budgeting Marginal Analysis (PBMA), which
      facilitates explicit, transparent decisions, from the bottom-up. Nurse managers
      need to weigh up competing demands on resources and decide in ways which maximize
      health gain. Economic evaluation can help here because it presents evidence to
      challenge or support existing allocations, and provides a systematic framework to
      analyse health care decisions. In the current context of competition for scarce
      resources, we suggest that nurse managers need to embrace these techniques, or be
      marginalized from the resource allocation process.

PMID- 16108781
TI  - Economic evaluation of a nursing-led inpatient unit: the impact of findings on
      management decisions of service utility and sustainability.
AB  - AIMS: The nursing-led inpatient unit is designed to substitute for a period of
      care in acute hospital wards and to improve patient outcome prior to discharge to
      the community. This paper aims to evaluate the cost, from the UK National Health
      Service perspective, of transfer to a nursing-led inpatient unit for intermediate
      care and to discuss the impact of these findings to the future development and
      sustainability of the nursing-led inpatient unit. BACKGROUND: Recent economic
      analyses have showed that nursing-led inpatient units are associated with
      increased costs of care with length of stay as the main driver of inpatient
      costs. METHOD: The cost-effectiveness analysis was part of a randomized
      controlled trial with a sample size of 175, of which 89 were in the nursing-led
      inpatient unit arm and 86 in the control arm. Resource use data included length
      of stay, investigations performed, multiprofessional input and nursing input.
      Clinical outcome was measured using Barthel Index, a functional status measure.
      RESULTS: Cost per day was lower on the nursing-led inpatient unit although cost
      per hospital stay was higher due to significantly increased length of stay.
      Postdischarge community care costs were lower. The incremental cost-effectiveness
      ratio of the treatment was 1044 pounds sterling per point improvement of the
      Barthel Index. CONCLUSIONS: The nursing-led inpatient unit was associated with
      higher costs however, the question of whether the nursing-led inpatient unit is
      cost-effective has not been clearly answered because of the limited follow-up
      period of the study. The increased cost of care on the nursing-led inpatient unit
      was not a major factor in local management decisions about the future of the
      unit. The changes in the context of service provision within which the nursing
      led inpatient unit operated as a result of substantial investment in intermediate
      care did have a major impact.

PMID- 16108782
TI  - Foundation Trusts: economics in the 'postmodern hospital'.
AB  - Foundation Trust Hospitals are community-controlled health care providers which
      have increased autonomy about how they produce outcomes for the British National
      Health Service. Although there is a literature on hospital economics it is
      unclear how these innovative providers will behave, if they have to compete for
      scarce resources with other hospitals. This paper reviews some of the earlier
      theories, such as the neoclassical theory of the firm, and discusses their
      relevance along with 'newer' economic theories such as the transaction costs and
      evolutionary theory of the firm, plus organizational and human resources theory,
      to the performance of Foundation Trusts. Much contemporary health care provision
      is shaped along modernist lines, using scientific endeavour to maximize the
      impact on health outcomes and technical and social efficiency. However, there is
      an increasingly postmodern standpoint--critical of modernity--being taken by both
      patients and hospital staff, to deconstruct processes in the organizations that
      serve them. Foundation Trusts are postmodern hospitals insomuch as they (to
      attract scarce resources in a competitive environment), need to marshal the
      diverse theories of the firm together in order to provide a mass-customized,
      quality experience, transparently and at least cost--whilst maintaining a stable
      organizational culture for staff.

PMID- 16108784
TI  - Molecular beacon: a multitask probe.

PMID- 16108785
TI  - Effect of pulsed ultrasound in combination with gentamicin on bacterial viability
      in biofilms on bone cements in vivo.
AB  - AIMS: The aim of this study is to investigate whether pulsed ultrasound (US) in
      combination with gentamicin yields a decreased viability of bacteria in biofilms
      on bone cements in vivo. METHODS AND RESULTS: Bacterial survival on bone cement
      in the presence and absence of ultrasound was compared in a rabbit model. Two
      bone cement samples with an Escherichia coli ATCC 10798 biofilm were implanted in
      a total of nine rabbits. In two groups bone cement discs loaded with gentamicin,
      freshly prepared and aged were used, and in one group unloaded bone cement discs
      in combination with systemically administered gentamicin. Pulsed ultrasound with
      a frequency of 28.48 kHz and a maximum acoustic intensity of 500 mW cm(-2) was
      applied continuously from 24 h till 72 h postsurgery on one of the two implanted
      discs. After euthanization and removal of the bacteria from the discs, the number
      of viable bacteria were quantified and skin samples were analysed for
      histopathological examination. Application of ultrasound, combined with
      gentamicin, reduced the viability of the biofilms in all three groups varying
      between 58 and 69% compared with the negative control. Histopathological
      examinations showed no skin lesions. CONCLUSIONS: Ultrasound resulted in a
      tendency of improved efficacy of gentamicin, either applied locally or
      systemically. Usage of ultrasound in this model proved to be safe. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study implies that ultrasound could improve the
      prevention of infection immediately after surgery, especially because the
      biomaterials, gentamicin and ultrasound used in this model are all in clinical
      usage, but not yet combined in clinical practice.

PMID- 16108786
TI  - Inactivation of Escherichia coli O157:H7 in biofilm on stainless steel by
      treatment with an alkaline cleaner and a bacteriophage.
AB  - AIMS: To determine the effectiveness of an alkaline cleaner used in food
      processing plants and a lytic bacteriophage specific for Escherichia coli O157:H7
      in killing wild type and rpoS-deficient cells of the pathogen in a biofilm.
      METHODS AND RESULTS: Wild type and rpoS-deficient cells were attached to
      stainless steel coupons (c. 7-8 log CFU per coupon) on which biofilms were
      developed during incubation at 22 degrees C for 96 h in M9 minimal salts media
      (MSM) with one transfer to fresh medium. Coupons were treated with 100 and 25%
      working concentrations of a commercial alkaline cleaner (pH 11.9, with 100 microg
      ml(-1) free chlorine) used in the food industry, chlorine solutions (50 and 100
      microg ml(-1) free chlorine), or sterile deionized water (control) at 4 degrees C
      for 1 and 3 min. Treatment with 100% alkaline cleaners reduced populations by 5-6
      log CFU per coupon, a significant (P < or = 0.05) reduction compared with
      treatment with water. Initial populations (2.6 log CFU per coupon) of attached
      cells of both strains were reduced by 1.2 log CFU per coupon when treated with
      bacteriophage KH1 (7.7 log PFU ml(-1)) for up to 4 days at 4 degrees C. Biofilms
      containing low populations (2.7-2.8 log CFU per coupon) of wild type and rpoS
      deficient cells that had developed for 24 h at 22 degrees C were not decreased by
      more than 1 log CFU per coupon when treated with KH1 (7.5 log PFU ml(-1)) at 4
      degrees C. CONCLUSIONS: Higher numbers of cells of E. coli O157:H7 in biofilms
      are killed by treatment with an alkaline cleaner than with hypochlorite alone,
      possibly through a synergistic mechanism of alkaline pH and hypochlorite.
      Populations of cells attached on coupons were reduced by treating with
      bacteriophage but cells enmeshed in biofilms were protected. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The alkaline pH, in combination with hypochlorite, in a
      commercial cleaner is responsible for killing E. coli O157:H7 in biofilms.
      Treatment with bacteriophage KH1 reduces populations of cells attached to coupon
      surfaces but not cells in biofilms.

PMID- 16108787
TI  - Factors affecting the inactivation of micro-organisms by intense light pulses.
AB  - AIM: To determine the influence of several factors on the inactivation of micro
      organisms by intense light pulses (ILP). METHODS AND RESULTS: Micro-organisms on
      agar media were flashed 50 times under different conditions and their
      inactivation measured. Micro-organisms differed in sensitivity to ILP but no
      pattern was observed among different groups. Several enumeration methods to
      quantify the effect of ILP were investigated and showed relevant differences,
      shading effect and photoreactivation accounted for them, the strike method
      yielded the most reliable results. Higher decontamination efficiencies were
      obtained for Petri dishes located close to the strobe and inside the illumination
      cone. Decontamination efficacy decreased significantly at contamination levels
      >6.85 log(10). After 13 successive treatments, no resistance to ILP could be
      demonstrated. Media warming up depended on the distance from the strobe and the
      number of flashes. CONCLUSIONS: For an industrial implementation: the position
      and orientation of strobes in an unit will determine the lethality, products
      should be flashed as soon as possible after contamination occurs, a cooling
      system should be used for heat-sensitive products and flashed products should be
      light protected. No resistant flora is expected to develop. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Conclusions derived from this work will allow a better
      implementation of this decontamination technique at industrial level.

PMID- 16108788
TI  - Sourcing faecal pollution from onsite wastewater treatment systems in surface
      waters using antibiotic resistance analysis.
AB  - AIMS: To identify the sources of faecal contamination in investigated surface
      waters and to determine the significance of onsite wastewater treatment systems
      (OWTS) as a major contributor to faecal contamination. METHODS AND RESULTS:
      Antibiotic resistance patterns (ARP) were established for a library of 717 known
      Escherichia coli source isolates obtained from human, domesticated animals,
      livestock and wild sources. Eight commonly used antibiotics, including
      amoxicillin, cephalothin, erythromycin, gentamicin, ofloxacin, chlortetracycline,
      tetracycline and moxalactam, at four different concentrations were used to obtain
      ARPs for E. coli isolates. Discriminant analysis (DA) was used to differentiate
      between the ARP of sources isolates. The developed ARP library was found to be
      adequate for discriminating human from nonhuman isolates, and was used to
      classify 256 enumerated E. coli isolates collected from monitored surface water
      locations. CONCLUSIONS: The resulting ARP DA indicated that a majority of the
      faecal contamination in more rural areas was nonhuman; however, the percentage of
      human isolates increased significantly in urbanized areas using OWTS for
      wastewater treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study signifies
      the feasibility of using ARP for source tracking faecal contamination in surface
      waters, and linking faecal contamination to OWTS. The information will enable
      regulatory authorities to implement appropriate management practices to reduce
      the contamination of water resources caused by high densities and failing OWTS.

PMID- 16108789
TI  - Nutritional requirements of mycelial growth of Cordyceps sinensis in submerged
      culture.
AB  - AIMS: The nutritional requirements for mycelial growth of Cordyceps sinensis in
      semi-synthetic liquid media were investigated. The results provide a basis for
      further physiological study and industrial fermentation of the fungus. METHODS
      AND RESULTS: Nutritional requirements, including 17 carbohydrates, 16 nitrogen
      compounds, nine vitamins, four macro-elements, four trace-elements and eight
      ratios of carbon to nitrogen, were studied for their effects on the mycelial
      growth in submerged cultures of C. sinensis by using one-factor-at-a-time and
      orthogonal matrix methods. Among these variables, sucrose, peptone, folic acid,
      calcium, zinc and a carbon to nitrogen ratio 12 : 1 were identified as the
      requirements for the optimum mycelial growth. The concentrations of sucrose,
      peptone and yeast extract were optimized and the effects of medium composition on
      mycelial growth were found to be in the order sucrose > yeast extract > peptone.
      The optimal concentration for mycelial growth was determined as 50 g l(-1)
      sucrose, 10 g l(-1) peptone and 3 g l(-1) yeast extract. CONCLUSIONS: Under
      optimal culture conditions, over 22 g l(-1) of mycelial biomass could be obtained
      after 40 days in submerged cultures. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Cordyceps sinensis, one of the most valued medicinal fungi, is shown to grow in
      axenic culture. This is the first report on nutritional requirements and design
      of a simplified semi-synthetic medium for mycelial growth of this psychrophilic
      species, which grows slowly below 20 degrees C. The results of this study will
      facilitate research on mass production of the fungus under defined culture
      conditions.

PMID- 16108790
TI  - Intrinsic tolerance of Bifidobacterium species to heat and oxygen and survival
      following spray drying and storage.
AB  - AIMS: This study examined the tolerance of various species of the genus
      Bifidobacterium to heat and oxygen and evaluated the survival of selected strains
      following spray drying and during storage. METHODS AND RESULTS: Nine
      Bifidobacterium species were considered to be relatively tolerant to both heat
      and oxygen and mostly segregated into two clusters within the 16S rDNA
      phylogenetic tree. Four species were tolerant to oxygen and 12 species were
      considered sensitive to oxygen and heat. Using a skimmed milk-based carrier good
      survival following spray drying and storage at 4 degrees C correlated with
      tolerance to heat and oxygen. Viability was inversely related to storage
      temperature and at 15 degrees C and 25 degrees C, a significant decline was
      observed for all species. The inclusion of gum acacia had no significant affect
      on survival or viability. However, using a fluidized-bed spray dryer viability
      was greatly improved. CONCLUSIONS: A group of closely related species tolerant to
      heat and oxygen had high survival following spray drying and maintained viability
      during prolonged storage at 4 degrees C. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Spray drying is a suitable method for the production of skimmed milk powder
      enriched with high numbers of viable bifidobacteria.

PMID- 16108792
TI  - Study of beta-glucosidase production by wine-related yeasts during alcoholic
      fermentation. A new rapid fluorimetric method to determine enzymatic activity.
AB  - AIMS: The beta-glucosidase activity is involved in the hydrolysis of several
      important compounds for the development of varietal wine flavour. The aim of the
      present study was to investigate the production of beta-glucosidase in a number
      of wine-related yeast strains and to measure and identify this activity over the
      course of grape juice fermentation. METHODS AND RESULTS: beta-glucosidase
      activity was measured as the amount of 4-methylumbelliferone released from 4
      methylumbelliferyl-beta-d-glucopyranoside substrate. Intact cells of some grape
      and wine-spoilage yeasts showed beta-glucosidase activity much higher than those
      observed in wine yeasts "sensu stricto". During fermentation, three Saccharomyces
      cerevisiae strains, one Hanseniaspora valbyensis strain and one Brettanomyces
      anomalus strain showed beta-glucosidase activity both intra- and extracellularly.
      CONCLUSIONS: In the studied strains, beta-glucosidase activity was at its maximum
      when the cells were in the active growth phase. However, a lowering of medium pH
      to values around 3 during fermentation led to total loss of activity.
      SIGNIFICANCE AND IMPACT OF THE STUDY: During the course of this study, a new,
      rapid and reproducible method to assay beta-glucosidase activity was developed.
      The fact that Saccharomyces and non-Saccharomyces yeast strains are able to
      express beta-glucosidase activity during the alcoholic fermentation sheds new
      light on the contribution of these yeasts in the aroma expression of wines.

PMID- 16108791
TI  - Molecular survey of aeroplane bacterial contamination.
AB  - AIMS: To examine bacterial contamination of passenger aircraft and to identify
      aeroplane environments posing the greatest potential health risk. METHODS AND
      RESULTS: DNA was extracted from ten environmental samples collected on four
      different flights (three domestic, one international) from a variety of surfaces
      frequently touched by passengers. PCR clone libraries were made from the DNA
      samples using bacterial-specific 16S ribosomal DNA (rDNA) primers. A total of 271
      bacterial rDNA sequences were obtained. We used BLAST analysis of the rDNA clone
      sequences to identify sequences in Genbank with the highest sequence similarity.
      The majority of the rDNA clones obtained from aeroplane environments were more
      than 97% identical to rDNA sequences from cultured bacterial species. Samples
      collected from the cabin surfaces (e.g., tray tables and arm rests) had
      undetectable levels of DNA and produced no PCR products. Bacterial diversity was
      highest on lavatory surfaces, including door handles, toilet handles, and sink
      faucets. Sequence data from these surfaces detected species from 58 different
      bacterial genera, and many of the best BLAST hits matched rDNA sequences of
      cultured species known to be opportunistic pathogens. The most frequently
      observed species came from five genera commonly associated with humans:
      Streptococcus, Staphylococcus, Cornybacterium, Proprionibacterium and Kocuria.
      CONCLUSIONS: The results show that there is a large diversity of bacterial
      contamination on aeroplanes, including organisms known to be opportunistic
      pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results indicate that
      aeroplanes have the potential to spread an enormous diversity of bacterial
      species among passengers and destinations. Aeroplane lavatories present an
      especially significant concern to public health.

PMID- 16108793
TI  - Aflatoxin biosynthesis gene clusters and flanking regions.
AB  - AIMS: To compare the biosynthetic gene cluster sequences of the main aflatoxin
      (AF)-producing Aspergillus species. METHODS AND RESULTS: Sequencing was on fosmid
      clones selected by homology to Aspergillus parasiticus sequence. Alignments
      revealed that gene order is conserved among AF gene clusters of Aspergillus
      nomius, A. parasiticus, two sclerotial morphotypes of Aspergillus flavus, and an
      unnamed Aspergillus sp. Phylogenetic relationships were established using the
      maximum likelihood method implemented in PAUP. Based on the
      Eurotiomycete/Sordariomycete divergence time, the A. flavus-type cluster has been
      maintained for at least 25 million years. Such conservation of the genes and gene
      order reflects strong selective constraints on rearrangement. Phylogenetic
      comparison of individual genes in the cluster indicated that ver-1, which has
      homology to a melanin biosynthesis gene, experienced selective forces distinct
      from the other pathway genes. Sequences upstream of the polyketide synthase
      encoding gene vary among the species, but a four-gene sugar utilization cluster
      at the distal end is conserved, indicating a functional relationship between the
      two adjacent clusters. CONCLUSIONS: The high conservation of cluster components
      needed for AF production suggests there is an adaptive value for AFs in character
      shaping niches important to those taxa. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first comparison of the complete nucleotide sequences of gene
      clusters harbouring the AF biosynthesis genes of the main AF-producing species.
      Such a comparison will aid in understanding how AF biosynthesis is regulated in
      experimental and natural environments.

PMID- 16108794
TI  - Decrease of enteric micro-organisms from rural sewage sludge during their
      composting in straw mixture.
AB  - AIMS: To study the decrease of enteric micro-organisms including viable nematode
      eggs, enteroviruses, faecal indicators (Escherichia coli and enterococci) and
      pathogenic bacteria (Listeria monocytogenes, Salmonella sp. and Clostridium
      perfringens) of a rural sewage sludge when it is composted for 7 months in
      mixture with straw. METHODS AND RESULTS: Numbers of the test organisms and the
      physico-chemical parameters were measured on a monthly basis on the mixture, on
      the compost after being turned, and on the pile in three positions representing
      the part by which air is incoming, the bottom of the pile and the part through
      which air is outgoing. The lowest temperature in the pile was observed at the
      bottom, where it did not exceed 50 degrees C against 66 degrees C in the two
      other areas. There were no significant differences between the three areas in
      terms of micro-organism survival. Infectious enteroviruses were inactivated
      rapidly and were not found after the first turning whereas some genomes were
      detected until after the third turning. Escherichia coli and enterococci
      presented a similar survival rate and their number decreased by 4 log(10) whereas
      Salmonella decayed at a greater rate than L. monocytogenes. The numbers of C.
      perfringens decreased gradually to reach a final concentration in the mature
      compost of about 10(2) CFU g(-1) dry matter (d.m.), which was similar to that of
      the faecal indicators. CONCLUSIONS: The hygienic effect of sludge composting in
      mixture with straw results in a significant reduction of enteric micro-organisms,
      the concentration of the faecal indicators in the final product being < 64 most
      probable number g(-1) d.m. The concentrations of Salmonella, enteroviruses and
      viable nematode eggs in the final product were not detectable which is in
      accordance with the French legislation. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      results which pointed out the different behaviour of the test micro-organisms
      reflect the difficulty to propose a relevant indicator of hygienization.
      Otherwise, they show that composting is an efficient means for hygienization of
      sludge of rural wastewater treatment, where the straw is available close to their
      place of production.

PMID- 16108795
TI  - Pilot-scale production and liquid formulation of Rhodotorula minuta, a potential
      biocontrol agent of mango anthracnose.
AB  - AIMS: To develop a pilot-plant fermentation process for the production of the
      yeast Rhodotorula minuta, to be used as a biocontrol agent of mango anthracnose,
      using a low-cost culture medium. To develop a stable liquid formulation that
      preserve high viability of the yeast stored at 4 degrees C. METHODS AND RESULTS:
      Keeping constant the volumetric power input, a fermentation process was scaled-up
      from shake flasks to a 100 l bioreactor. Preharvest applications of the yeast
      resulted in postharvest anthracnose severity equal or lower than that observed
      with a chemical fungicide. Glycerol was added to the formulation as water
      activity reducer and xanthan gum as a viscosity-enhancing agent. Yeast initial
      concentration of 10(10) CFU ml(-1) resulted in 4-5 orders of magnitude decrease
      after 1 month of storage at 4 degrees C, whereas when it was formulated at 10(9)
      CFU ml(-1), the decrease was of two orders of magnitude in 6 months. CONCLUSIONS:
      The fermentation process was successfully scaled-up using a low-cost culture
      medium. Postharvest anthracnose severity could be considerably reduced using this
      yeast. Formulating the yeast at 10(9) CFU ml(-1) and adding glycerol (20%) and
      xanthan (5 g l(-1)) avoided both contamination and yeast sedimentation and it was
      able to preserve up to 10(7) CFU ml(-1) after 6 months at 4 degrees C.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The yeast R. minuta is reported as a novel
      antagonistic micro-organism against the pathogen Colletotrichum gloeosporioides.
      Pilot plant production of this yeast allowed us to conduct field tests in
      commercial orchards during three harvest seasons. Yeast suspensions applied to
      mango trees reduced the fruit anthracnose severity in levels similar or better
      than chemical fungicides.

PMID- 16108796
TI  - Role of the N-terminal polycystic kidney disease domain in chitin degradation by
      chitinase A from a marine bacterium, Alteromonas sp. strain O-7.
AB  - AIMS: The aim of study was to clarify whether the polycystic kidney disease (PKD)
      domain of chitinase A (ChiA) participates in the hydrolysis of powdered chitin.
      METHODS AND RESULTS: Site-directed mutagenesis of the conserved aromatic residues
      of PKD domain was performed by PCR. The aromatic residues, W30, Y48, W64 and W67,
      were replaced by alanine, and single- and double-mutant chitinases were produced
      in Escherichia coli XL10 and purified with HisTrap column. Single mutations were
      not quite effective on the hydrolysing activities against chitinous substrates
      when compared with wild-type ChiA. However, mutations of W30 and W67 decreased
      the activities against powdered chitin by 87.6%. Wild-type and mutant PKD domains
      were produced in E. coli TOP10 and purified with glutathione-Sepharose 4B column.
      Wild-type PKD domain showed significant binding activity to powdered chitin,
      whereas mutations of W30 and W67 reduced the binding activity to powdered chitin
      drastically. These results suggest that PKD domain of ChiA is essential for
      effective hydrolysis of powdered chitin through the interaction between two
      aromatic residues and chitin molecule. CONCLUSIONS: PKD domain of ChiA
      participates in the effective hydrolysis of powdered chitin through the
      interaction between two aromatic residues (W30 and W67) and chitin molecule.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of this study provide
      important information on chitin degradation by microbial chitinases.

PMID- 16108797
TI  - Optimization of a rapid method for studying the cellular location of beta
      glucosidase activity in wine yeasts.
AB  - AIMS: To improve a method for determining beta-glucosidase activity and to apply
      it in yeasts isolated from wine ecosystems from "La Mancha" region and to know
      its cellular location. METHODS AND RESULTS: A total of 82 wine yeasts were
      identified (PCR/RFLP) and evaluated for their beta-glucosidase activity. First,
      they were qualitatively evaluated by growth on YNB cellobiose, the activity was
      quantified using different culture media, under aerobic and anaerobic conditions
      and cells after 24-72 h of growth. To study the location activity, five fractions
      were obtained (supernatant, whole cell, cell wall, cytosol and cell membrane).
      The enzymatic assays were optimized, being: growth in YP cellobiose for 72 h in
      aeration conditions and, after cell removing, enzyme analysis with 128 g l(-1) of
      cellobiose as substrate, for 30 min at 30 degrees C. The genus that displayed the
      greatest activity were Pichia, Hanseniaspora and Rhodotorula, and the activity
      was intracellular. CONCLUSIONS: The study showed that beta-glucosidase activity
      was induced by the carbon source and was aerobic dependent. The non-Saccharomyces
      species displayed the greatest activity, which was intracellular and strain
      dependent. SIGNIFICANCE AND IMPACT OF THE STUDY: This study developed a reliable
      method for screening beta-glucosidase activity in yeasts isolated from wine
      ecosystems. This activity is very important in the release of monoterpenols from
      glycoside precursors for the enhancement of wine aromas.

PMID- 16108798
TI  - Studies on growth and metabolism of Oenococcus oeni on sugars and sugar mixtures.
AB  - AIMS: To study the effect of sugars and sugar mixtures on the growth kinetics of
      Oenococcus oeni NCIMB 11648 in batch culture with the aim of producing a high
      cell productivity system for starter cultures. METHODS AND RESULTS: The growth of
      O. oeni was investigated on single sugars (glucose, fructose or sucrose) and
      their mixtures (glucose-fructose, glucose-sucrose or fructose-sucrose). Better
      growth was obtained on sugar mixtures compared with growth on a single sugar. The
      production system of O. oeni biomass was investigated in batch culture with or
      without pH control with respect to kinetics, specific growth rate and biomass
      yield. The effect of pH and substrate concentration on fermentation balances and
      ATP yield were determined. The optimal growth of O. oeni was achieved on the
      glucose-fructose mixture (9 g l(-1), 1 : 1) at pH 4.5 and 25 degrees C with pH
      control, with highest cell volumetric productivity (7.9 mg cell l(-1) h(-1)),
      biomass yield (0.041 g cell g(-1) sugar) and specific growth rate (0.066 h(-1)).
      CONCLUSIONS: The limitations to the growth of O. oeni were pH and inhibition by
      end product resulting in poor utilization of the medium with low cell yields. The
      cell productivity of the system can be improved by the appropriate use of mixed
      sugar growth medium. SIGNIFICANCE AND IMPACT OF THE STUDY: This study uniquely
      showed that appropriate sugar mixtures with the correct environmental conditions
      can significantly improve the productivity of O. oeni cultures.

PMID- 16108799
TI  - Growth and survival of bacteria implicated in sudden infant death syndrome on cot
      mattress materials.
AB  - AIMS: To compare growth and survival of selected bacteria implicated in sudden
      infant death syndrome (SIDS) on cot mattress polyurethane (PU) inner-foams and on
      different types of cot mattress cover materials. METHODS AND RESULTS: Escherichia
      coli, Staphylococcus aureus or Streptococcus pyogenes were inoculated onto
      swatches of new-unused cot mattress PU inner-foam and onto three types of cot
      mattress covers (polyvinyl chloride, cotton and polyester). The influence of
      inoculation cell density, relative humidity (RH) and temperature of incubation on
      survival was assessed by recovery of cells in 0.85% NaCl, with viable cell
      enumeration by plate counting on selective and differential media. Utilization of
      carbon and nitrogen sources within cot mattress PU was assessed by following
      growth on aqueous leachate from PU, and by colorimetric determination of aromatic
      amines. Good survival capability (>206 d) was shown by all three test species on
      PU inner-foam and on polyester mattress cover at high RH (75%), but only by
      Staph. aureus on PU at low RH (25%). Aqueous soluble material from PU foam
      supports bacterial growth; removal of aromatic amines from aqueous leachate from
      PU accompanies growth of Staph. aureus. CONCLUSIONS: Staphylococcus aureus has
      good survival capability on cot mattress PU foam, even at low RH. Soluble
      material within PU can serve as carbon and nitrogen sources for bacterial growth.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Prolonged survival of Staph. aureus on PU
      at low RH could explain, in the context of the common bacterial toxins
      hypothesis, an increased risk of SIDS associated with used infant mattresses.

PMID- 16108800
TI  - Which lactic acid bacteria are responsible for histamine production in wine?
AB  - AIMS: To quantify the ability of 136 lactic acid bacteria (LAB), isolated from
      wine, to produce histamine and to identify the bacteria responsible for histamine
      production in wine. METHODS AND RESULTS: A qualitative method based on pH changes
      in a plate assay was used to detect wine strains capable of producing high levels
      of histamine. Two quantitative, highly sensitive methods were used, an enzymatic
      method and HPLC, to quantify the histamine produced by LAB. Finally, an improved
      PCR test was carried out to detect the presence of histidine decarboxylase gene
      in these bacteria. The species exhibiting the highest frequency of histamine
      production is Oenococcus oeni. However, the concentration of histamine produced
      by this species is lower than that produced by strains belonging to species of
      Lactobacillus and Pediococcus. A correlation of 100% between presence of
      histidine decarboxylase gene and histamine production was observed. Wines
      containing histamine were analysed to isolate and characterize the LAB
      responsible for spoilage. CONCLUSIONS: Oenococcus was able to synthesize low
      concentrations of histamine in wines, while Pediococcus parvulus and
      Lactobacillus hilgardii have been detected as spoilage, high histamine-producing
      bacteria in wines. SIGNIFICANCE AND IMPACT OF THE STUDY: Information regarding
      histamine-producing LAB isolated from wines can contribute to prevent histamine
      formation during winemaking and storage.

PMID- 16108801
TI  - Detection of Mycobacterium avium subspecies paratuberculosis in Swiss dairy
      cattle by real-time PCR and culture: a comparison of the two assays.
AB  - AIMS: To compare the two different diagnostic assays for the detection of
      Mycobacterium avium ssp. paratuberculosis, the aetiological agent of
      paratuberculosis. METHODS AND RESULTS: Faecal samples were derived from 310 cows,
      representing 13 commercial dairy herds in various locations in Switzerland with
      expected increased risk because of a past history of disease. Detection assays
      for M. avium ssp. paratuberculosis were culture (gold standard) and a newly
      designed real-time PCR. Real-time PCR identified 31 of 310 animals as positive
      within this risk population whereas culture identified 20 positive animals. The
      specificity of real-time PCR was confirmed by DNA sequencing of the PCR product.
      Depending on the test used, the paratuberculosis prevalence in our tested risk
      population ranged from 6.5 to 10%. CONCLUSIONS: Real-time PCR and culture data
      were in good agreement, and real-time PCR generates data in a short time in
      contrast to culture. SIGNIFICANCE AND IMPACT OF THE STUDY: We consider real-time
      PCR as a suitable alternative method to culture for the detection of M. avium
      ssp. paratuberculosis in a national surveillance programme.

PMID- 16108802
TI  - Enumeration and speciation of enterococci found in marine and intertidal
      sediments and coastal water in southern California.
AB  - AIMS: To determine the levels and species distribution of enterococci in
      intertidal and marine sediments and coastal waters at two beaches frequently in
      violation of bacterial water standards. METHODS AND RESULTS: Faecal indicator
      bacteria were extracted from sediment and enumerated using membrane filtration.
      High levels of enterococci were detected in intertidal sediments in a seasonal
      river and near a storm drain outlet. Low levels were found in marine sediments at
      10 m depths and in surf zone sand. Bacterial isolates presumptively identified as
      Enterococcus on mEI media were speciated. The predominant species found in both
      water and sediment included Enterococcus faecalis, Enterococcus faecium,
      Enterococcus hirae, Enterococcus casseliflavus and Enterococcus mundtii. A number
      of isolates (11-26%) from regulatory water samples presumptively identified as
      enterococci on mEI media were subsequently identified as species other than
      Enterococcus. At both study sites, the distribution of species present in water
      was comparable with those in sediments and the distribution of species was
      similar in water samples passing and exceeding bacterial indicator standards.
      CONCLUSIONS: High levels of Enterococcus in intertidal sediments indicate
      retention and possible regrowth in this environment. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Resuspension of enterococci that are persistent in sediments may cause
      beach water quality failures and calls into question the specificity of this
      indicator for determining recent faecal contamination.

PMID- 16108803
TI  - Use of RAPD and killer toxin sensitivity in Saccharomyces cerevisiae strain
      typing.
AB  - AIMS: Two different strain characterization techniques, random amplified
      polymorphic DNA (RAPD) and killer toxin sensitivity (KTS), were compared to
      assess their typing performance using a set of 30 certified Saccharomyces
      cerevisiae strains. METHODS AND RESULTS: A sequential random resampling procedure
      was employed to subdivide the 32 descriptors in eight sets, in order to compare
      the differential performances of the two techniques with diverse number of
      characters. Results showed that RAPD performs better than killer, although the
      complete differentiation of the strains under study could be obtained only by
      combining profiles from the two techniques. CONCLUSIONS: The combination of
      different typing techniques was useful when discriminating similar organisms. In
      such cases, the introduction of a second typing technique can be more
      advantageous than increasing the number of characters obtained with a single
      method. SIGNIFICANCE AND IMPACT OF THE STUDY: The distribution of among-strains
      pairwise distances and the relative performance of the two techniques has
      implications for the study of biodiversity, taxonomy and microbial ecology.

PMID- 16108804
TI  - Evaluation of antibiotic resistance analysis and ribotyping for identification of
      faecal pollution sources in an urban watershed.
AB  - AIMS: The accuracy of ribotyping and antibiotic resistance analysis (ARA) for
      prediction of sources of faecal bacterial pollution in an urban southern
      California watershed was determined using blinded proficiency samples. METHODS
      AND RESULTS: Antibiotic resistance patterns and HindIII ribotypes of Escherichia
      coli (n = 997), and antibiotic resistance patterns of Enterococcus spp. (n =
      3657) were used to construct libraries from sewage samples and from faeces of
      seagulls, dogs, cats, horses and humans within the watershed. The three libraries
      were analysed to determine the accuracy of host source prediction. The internal
      accuracy of the libraries (average rate of correct classification, ARCC) with six
      source categories was 44% for E. coli ARA, 69% for E. coli ribotyping and 48% for
      Enterococcus ARA. Each library's predictive ability towards isolates that were
      not part of the library was determined using a blinded proficiency panel of 97 E.
      coli and 99 Enterococcus isolates. Twenty-eight per cent (by ARA) and 27% (by
      ribotyping) of the E. coli proficiency isolates were assigned to the correct
      source category. Sixteen per cent were assigned to the same source category by
      both methods, and 6% were assigned to the correct category. Addition of 2480 E.
      coli isolates to the ARA library did not improve the ARCC or proficiency
      accuracy. In contrast, 45% of Enterococcus proficiency isolates were correctly
      identified by ARA. CONCLUSIONS: None of the methods performed well enough on the
      proficiency panel to be judged ready for application to environmental samples.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Most microbial source tracking (MST)
      studies published have demonstrated library accuracy solely by the internal ARCC
      measurement. Low rates of correct classification for E. coli proficiency isolates
      compared with the ARCCs of the libraries indicate that testing of bacteria from
      samples that are not represented in the library, such as blinded proficiency
      samples, is necessary to accurately measure predictive ability. The library-based
      MST methods used in this study may not be suited for determination of the
      source(s) of faecal pollution in large, urban watersheds.

PMID- 16108805
TI  - Community survey of ammonia-oxidizing bacteria in full-scale activated sludge
      processes with different solids retention time.
AB  - AIMS: To study the effects of different solids retention time (SRT) on the
      nitrification activity and community composition of ammonia-oxidizing bacteria
      (AOB) in two full-scale activated sludge processes during a 5-month period.
      METHODS AND RESULTS: The AOB community composition was analysed using
      fluorescence in situ hybridization (FISH) and denaturing gradient gel
      electrophoresis (DGGE), and the identified populations were enumerated by
      quantitative FISH. Potential nitrification rates were determined in batch tests
      and the in situ rates were calculated from mass balances of nitrogen in the
      plants. Increased SRT reduced the nitrification activity, but neither the number
      per mixed liquor suspended solids nor community composition of AOB were affected.
      Two dominant AOB populations related to Nitrosomonas europaea and Nitrosomonas
      oligotropha were identified by FISH, whereas only the latter could be detected by
      DGGE. CONCLUSIONS: The effect of a longer SRT on the activity was probably
      because of physiological changes in the AOB community rather than a change in
      community composition. SIGNIFICANCE AND IMPACT OF THE STUDY: Physiological
      alterations of a stable AOB community are possible and may stabilize activated
      sludge processes. The commonly used FISH probes designed to target all beta
      proteobacterial AOB does not detect certain Nitrosomonas oligotropha populations,
      leading to an underestimation of AOB if a wider set of probes is not used.

PMID- 16108806
TI  - Extracellular protease activity of different Pseudomonas strains: dependence of
      proteolytic activity on culture conditions.
AB  - AIMS: This study investigated the effect of growth conditions on proteolytic
      activity of a Pseudomonas strain, named Pseudomonas sp. LBSA1, isolated from bulk
      raw milk. It was compared with three Pseudomonas chlororaphis and one Pseudomonas
      fluorescens strain from culture collections. METHODS AND RESULTS: Bacteriae were
      grown in a minimal salt medium. For all the strains, addition of 1% (v/v) skim
      milk to the growth medium was sufficient to induce protease production in 48-h
      culture. Addition of 1 mmol l(-1) calcium chloride permitted the detection of
      proteolytic activity of four strains in 48-h cultures but not for Pseudomonas sp.
      LBSA1. The five strains presented two patterns of proteolytic activity when grown
      in the minimal salt medium supplemented with 2% (v/v) skim milk at various
      temperatures for 48 h. Two electrophoretic protease patterns were also obtained
      from the zymogram of extracellular medium for the five strains. CONCLUSIONS: The
      growth conditions permitting protease production are variable and do not depend
      on the genus of the producing strain. SIGNIFICANCE AND IMPACT OF THE STUDY: For
      the first time a study on proteolytic activity of P. chlororaphis strains is
      reported. Among the tested criteria, zymograms of extracellular medium were the
      only ones that permitted distinguishing the P. chlororaphis strains from the P.
      fluorescens strain.

PMID- 16108807
TI  - Purification and molecular characterization of antibacterial compounds produced
      by Lactobacillus murinus strain L1.
AB  - AIMS: The aim of this work was to purify and characterize antibacterial compounds
      produced by Lactobacillus murinus strain L1. METHODS AND RESULTS: Antagonistic
      activity was observed in a deferred agar-spot assay against spoilage and
      pathogenic bacteria, but not against lactobacilli. The inhibitory activity
      occurred between pH 3.0 and 5.0, and was heat stable. The active compounds were
      purified by gel filtration chromatography and two peaks of antibacterial activity
      were observed using Bacillus cereus ATCC 11778 and Shigella sonnei ATCC 11060 as
      indicator strains. Two active low molecular weight compounds were responsible for
      this phenomenon and UV spectroscopy, gas chromatography and mass spectrometry
      were used to characterize them. One of them is lactic acid, while the other is a
      mono-substituted aromatic ring apparently constituted by group residues of m/z
      192 linked in tandem to phenylalanine. CONCLUSIONS: Lactobacillus murinus
      produces at least two low molecular weight compounds active against B. cereus and
      Sh. sonnei. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first purification
      of a new broad-spectrum antibacterial compound from Lact. murinus which inhibits
      various pathogenic and food spoilage bacteria without acting on other
      lactobacilli. Using it as a biotechnological control agent of bacterial spoilage
      may be a promising possibility for the food industry.

PMID- 16108808
TI  - Analysis of 16S-23S intergenic spacer regions of the rRNA operons in Edwardsiella
      ictaluri and Edwardsiella tarda isolates from fish.
AB  - AIMS: To analyse interspecies and intraspecies differences based on the 16S-23S
      rRNA intergenic spacer region (ISR) sequences of the fish pathogens Edwardsiella
      ictaluri and Edwardsiella tarda. METHODS AND RESULTS: The 16S-23S rRNA spacer
      regions of 19 Edw. ictaluri and four Edw. tarda isolates from four geographical
      regions were amplified by PCR with primers complementary to conserved sequences
      within the flanking 16S-23S rRNA coding sequences. Two products were generated
      from all isolates, without interspecies or intraspecific size polymorphisms.
      Sequence analysis of the amplified fragments revealed a smaller ISR of 350 bp,
      which contained a gene for tRNA(Glu), and a larger ISR of 441 bp, which contained
      genes for tRNA(Ile) and tRNA(Ala). The sequences of the smaller ISR of different
      Edw. ictaluri isolates were essentially identical to each other. Partial
      sequences of larger ISR from several Edw. ictaluri isolates also revealed no
      differences from the one complete Edw. ictaluri large ISR sequence obtained. The
      sequences of the smaller ISR of Edw. tarda were 97% identical to the Edw.
      ictaluri smaller ISR and the larger ISR were 96-98% identical to the Edw.
      ictaluri larger ISR sequence. The Edw. tarda isolates displayed limited ISR
      sequence heterogeneity, with > or =97% sequence identity among isolates for both
      small and large ISR. CONCLUSIONS: There is a high degree of size and sequence
      similarity of 16S-23S ISR both among isolates within Edw. ictaluri and Edw. tarda
      species and between the two species. SIGNIFICANCE AND IMPACT OF THE STUDY: Our
      results confirm a close genetic relationship between Edw. ictaluri and Edw. tarda
      and the relative homogeneity of Edw. ictaluri isolates compared with Edw. tarda
      isolates. Because no differences were found in ISR sequences among Edw. ictaluri
      isolates, sequence analysis of the ISR will not be useful to distinguish isolates
      of Edw. ictaluri. However, we identified restriction sites that differ between
      ISR sequences of Edw. ictaluri and Edw. tarda, which will be useful in
      distinguishing the two species.

PMID- 16108809
TI  - In situ activity of a bacteriocin-producing Lactococcus lactis strain. Influence
      on the interactions between lactic acid bacteria during sourdough fermentation.
AB  - AIMS: To biochemically characterize the bacteriocin produced by Lactococcus
      lactis ssp. lactis M30 and demonstrate its effect on lactic acid bacteria (LAB)
      during sourdough propagation. METHODS AND RESULTS: A two-peptide bacteriocin
      produced by L. lactis ssp. lactis M30 was purified by ion exchange, hydrophobic
      interaction and reversed phase chromatography. Mass spectrometry of the two
      peptides and sequence analysis of the ltnA2 gene showed that the bacteriocin was
      almost identical to lacticin 3147. During a 20-day period of sourdough
      propagation the stability of L. lactis M30 was demonstrated, with concomitant
      inhibition of the indicator strain Lactobacillus plantarum 20, as well as the non
      interference with the growth of the starter strain Lact. sanfranciscensis CB1.
      CONCLUSIONS: In situ active bacteriocins influence the microbial consortium of
      sourdough LAB and can "support" the dominance of insensitive strains during
      sourdough fermentation. SIGNIFICANCE AND IMPACT OF THE STUDY: The in situ
      bacteriocinogenic activity of selected lactococci enables the persistence of
      insensitive Lact. sanfranciscensis strains, useful to confer good characteristics
      to the dough, at a higher cell concentration with respect to other LAB of the
      same ecosystem.

PMID- 16108810
TI  - In vitro effect of phenolic antioxidants on germination, growth and aflatoxin B
      accumulation by peanut Aspergillus section Flavi.
AB  - AIMS: The effectiveness of the food-grade antioxidants butylated hydroxytoluene
      (BHT), trihydroxybutyrophenone (THB), propyl paraben (PP) and butylated
      hydroxyanisole (BHA) at 1, 10 and 20 mmol l(-1) concentrations on germination,
      growth, and aflatoxin B(1) (AFB(1)) production by Aspergillus section Flavi
      strains was determined. METHODS AND RESULTS: Assays on the lag phase of
      germination, germination percentage, germ tube elongation rate, lag phase, growth
      rate and AFB(1) production by three strains of Aspergillus flavus and three of
      Aspergillus parasiticus were carried out in vitro on peanut extract meal agar
      conditioned at different water activities (a(w): 0.982, 0.971, 0.955, 0.937). The
      antioxidants PP and BHA efficiently inhibited the germination of the two species
      tested at the doses 10 and 20 mmol(-1). The antioxidants PP and BHA at 1 mmol l(
      1) and THB at 20 mmol l(-1) reduced the germ tube elongation rate most
      effectively, regardless of a(w) levels. An increase in the lag time and a
      reduction in the growth rate of 100% of the strains was observed, this was due to
      the action of BHT at the doses 10 and 20 mmol(-1) at 0.982, 0.971 and 0.955 a(w),
      although these treatments stimulated the AFB(1) accumulation in most of the fungi
      tested. The more effective antioxidants were PP and BHA, which increased the lag
      phase, reduced the growth rate and AFB(1) production in all of the strains at the
      four a(w) assayed. At concentrations 10 and 20 mmol l(-1), these antioxidants
      totally inhibited fungal development. CONCLUSIONS: The study shows that the
      antioxidants BHA and PP are effective fungal inhibitors to peanut Aspergillus
      section Flavi in wide range of water activity. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The results suggest that phenolic antioxidants, BHA and PP, can be
      effective fungitoxicants on aflatoxigenic strains in peanut at industrial level.

PMID- 16108811
TI  - Extracellular homopolysaccharides and oligosaccharides from intestinal
      lactobacilli.
AB  - AIMS: To characterize lactobacilli isolated from the intestines of ducks or pigs
      with respect to the production of extracellular homopolysaccharides (HoPS) and
      oligosaccharides. METHODS AND RESULTS: Lactobacillus strains of duck or pig
      origin were screened for HoPS synthesis and >25% of the isolates produced
      fructans or glucans from sucrose. Glucan-forming strains were found within the
      species Lactobacillus reuteri and Lactobacillus animalis and fructan-forming
      strains were found within Lactobacillus mucosae, Lactobacillus crispatus and
      Lactobacillus acidophilus. The glucan-forming strains of L. reuteri but not L.
      animalis produced glucose-oligosaccharides in additon to the respective polymers,
      and two fructan-forming strains of L. acidophilus produced kestose. Genes coding
      for glycosyltransferases were detected by PCR and partially characterized by
      sequence analysis. CONCLUSIONS: A large proportion of lactobacilli from
      intestinal habitats produce HoPS from sucrose and polysaccharide formation is
      generally associated with the formation of glucose- and fructose
      oligosaccharides. SIGNIFICANCE AND IMPACT OF THE STUDY: The characterization of
      the metabolic potential of intestinal lactobacilli contributes to the
      understanding of the molecular basis of autochthony in intestinal habitats.
      Moreover, this is the first report of glucose-oligosaccharide production during
      growth of lactobacilli, and one novel fructosyltransferase and one novel
      glucansucrase were partially characterized on the genetic level.

PMID- 16108812
TI  - Chemokine control of lymphocyte trafficking: a general overview.
AB  - Chemokines are a large family of small, generally secreted polypeptides which
      guide lymphocyte movement throughout the body by controlling integrin avidity and
      inducing migration. Here, we look at recent, exciting findings on chemokine
      function throughout lymphocyte development and co-ordinated T and B cell
      migration during immune responses. Finally, we will review data on the regional
      control of immunity by tissue-specific chemokine receptors on effector/memory
      lymphocytes.

PMID- 16108813
TI  - Differential responses of cord and adult blood-derived dendritic cells to dying
      cells.
AB  - Normal turnover of body tissues yields apoptotic cells while infections cause
      tissue injuries and cell necrosis. The interaction of these dying cells with
      dendritic cells (DCs) may provide immunological instructions leading to either
      immune tolerance or activation. We hypothesize that neonatal and adult DCs differ
      in their responses to dying cells, thereby contributing to the observed
      differences in immune responses between neonates and adults. We compare the
      outcome of interaction of cord and adult blood-derived DCs with dying Epstein
      Barr-virus-transformed lymphoblastoid cells (LCLs) and the responsiveness to
      lipopolysaccharide. While cord DCs were able to phagocytose both apoptotic and
      necrotic LCLs, the subsequent responses differed significantly from those of
      adult DCs. Interaction of adult DCs with necrotic but not early apoptotic LCLs
      resulted in high expression of DC costimulatory molecules (CD80/CD86) and
      activation markers (CD83), production of both proinflammatory and anti
      inflammatory cytokines (tumour necrosis factor-alpha, interleukin-10), and strong
      T-cell-stimulating activities. In contrast, in response to either necrotic or
      apoptotic LCLs, cord DCs had minimal up-regulation of those DC functional
      markers, little cytokine production and poor stimulation on T-cell proliferation.
      In response to lipopolysaccharide, however, both adult and cord DCs produced
      comparable levels of tumour necrosis factor-alpha and interleukin-10, but only
      adult DCs produced interleukin-12(p70). Taken together, these results suggest
      that neonatal DCs generally favour immune tolerance with minimal activation and
      cytokine production, except in extremely dangerous situations, such as bacterial
      sepsis, when neonatal DCs may produce certain types of cytokines and stimulate T
      cell proliferation.

PMID- 16108814
TI  - Detection, epitope-mapping and function of anti-Fas autoantibody in patients with
      silicosis.
AB  - Dysregulation of apoptosis through the Fas-Fas ligand pathway is associated with
      the onset of autoimmune disease. Since autoantibodies directed against unknown
      antigens are present in the sera of these patients, sera samples were examined
      for the presence of autoantibodies directed against the Fas molecule. Using
      Western blotting and a ProteinChip analysis, autoantibodies against Fas were
      detected in patients with silicosis, systemic lupus erythematosus (SLE) and
      systemic sclerosis (SSc), and weakly detected in healthy individuals. Using
      epitope mapping employing 12-amino-acid polypeptides with the SPOTs system, a
      minimum of four epitopes and a maximum of 10 epitopes were found. Several amino
      acid residues involved in binding FasL, such as C66, R87, L90, E93 and H126, were
      presented within the epitopes. Serum containing a large amount of anti-Fas
      autoantibody from silicosis patients inhibited the growth of a Fas-expressing
      human cell line, but did not inhibit the growth of a low Fas-expresser nor a Fas
      expresser in which the Fas gene had been silenced by small interference RNA. All
      epitopes in the intracellular region of Fas were located in the death domain. The
      possible roles of anti-Fas autoantibody detected in healthy volunteers and
      patients with silicosis or autoimmune diseases are discussed here.

PMID- 16108815
TI  - Phenotypical and functional alterations during the expansion phase of invariant
      Valpha14 natural killer T (Valpha14i NKT) cells in mice primed with alpha
      galactosylceramide.
AB  - Invariant Valpha14 natural killer T (Valpha14i NKT) cells are a unique
      immunoregulatory T-cell population that is restricted by CD1d. The glycolipid
      alpha-galactosylceramide (alpha-GalCer) is presented by CD1d and causes robust
      Valpha14i NKT-cell activation. Three days after injection of alpha-GalCer,
      Valpha14i NKT cells vigorously increase in number and then gradually decrease to
      normal levels. In the present study, we found that the re-administration of alpha
      GalCer into mice primed 3 days earlier causes a marked increase in serum
      interleukin-4 and interferon-gamma. Intracellular staining revealed that the only
      expanded Valpha14i NKT cells are responsible for the enhanced cytokine
      production. The enhanced cytokine production was correlated with an increased
      number of Valpha14i NKT cells after priming. Additionally, primed Valpha14i NKT
      cells produced larger amounts of cytokine as compared with naive Valpha14i NKT
      cells when cultured with alpha-GalCer-pulsed dendritic cells. Thus, we considered
      that a subset of expanded Valpha14i NKT cells acquired a strong ability to
      produce cytokines. In contrast to mice primed 3 days earlier, cytokine production
      is markedly diminished in mice primed 7 days earlier. The expanded Valpha14i NKT
      cells altered the surface phenotype (NK1.1- CD69-) and contained intracellular
      interferon-gamma. Additionally, we found that primed Valpha14i NKT cells did not
      disappear or down-regulate surface TCR expression when re-injected with alpha
      GalCer as compared with naive Valpha14i NKT cells. These results demonstrate that
      the function and surface phenotype of Valpha14i NKT cells is dramatically altered
      after alpha-GalCer priming.

PMID- 16108816
TI  - Characterization of the B-cell immune response elicited in BALB/c mice challenged
      with Neospora caninum tachyzoites.
AB  - Activation of B cells occurring in hosts infected with protozoan parasites has
      been implicated either in protective or parasite-evasion immune-mediated
      mechanisms. Intraperitoneal inoculation of Neospora caninum tachyzoites into
      BALB/c mice induces an acute response characterized by a rapid increase in the
      numbers of CD69-expressing peritoneal and splenic B cells. This early B-cell
      stimulatory effect preceded an increase in the numbers of total and
      immunoglobulin-secreting splenic B cells and a rise in serum levels of N. caninum
      specific immunoglobulins, predominantly of the immunoglobulin G2a (IgG2a) and IgM
      isotypes. Increased numbers of B cells expressing the costimulatory molecules
      CD80 and CD86 were also observed in the N. caninum-infected mice. The B-cell
      stimulatory effect observed in mice challenged with N. caninum tachyzoites was
      reduced in mice challenged with gamma-irradiated parasites. Contrasting with the
      peripheral B-cell expansion, a depletion of B-lineage cells was observed in the
      bone-marrow of the N. caninum-infected mice. Intradermal immunization of BALB/c
      mice with diverse N. caninum antigenic preparations although inducing the
      production of parasite-specific antibodies nevertheless impaired interferon-gamma
      (IFN-gamma) mRNA expression and caused lethal susceptibility to infection in mice
      inoculated with a non-lethal parasitic inoculum. This increased susceptibility to
      N. caninum was not observed in naive mice passively transferred with anti-N.
      caninum antibodies. Taken together, these results show that N. caninum induces in
      BALB/c mice a parasite-specific, non-polyclonal, B-cell response, reinforce
      previous observations made by others showing that immunization with N. caninum
      whole structural antigens increases susceptibility to murine neosporosis and
      further stress the role of IFN-gamma in the host protective immune mechanisms
      against this parasite.

PMID- 16108817
TI  - Identification of specific autoantigens in Sjogren's syndrome by SEREX.
AB  - We carried out SEREX (serological analysis of antigens by recombinant cDNA
      expression cloning) using sera from patients with Sjogren's syndrome (SjS) and
      investigated the frequencies of autoantibodies against autoantigens identified by
      SEREX in the sera of healthy individuals (HI) and patients with SjS, rheumatoid
      arthritis (RA) and systemic lupus erythematosus (SLE). IFI16 and two kelch-like
      proteins, KLHL12 and KLHL7, were found to be novel autoantigens in SjS by SEREX.
      A markedly high frequency of anti-IFI16 autoantibodies was observed in the sera
      of SjS (SjS, 70%; RA, 13%; SLE, 33%; HI, 0%). Interestingly, all serum samples
      from SjS demonstrated immunoreactivity against one or both of IFI16 and SS-B/La.
      The presence of autoantibodies against KLHL12 and KLHL7 in the sera was
      significantly specific to SjS (23% and 17%, respectively), as they were not
      detected in RA, SLE or HI. Furthermore, we confirmed that transcripts of these
      autoantigens were expressed preferentially in the salivary glands and immuno
      privileged testes. Our results suggest these autoantigens may be useful as
      serological markers for the clinical diagnosis of SjS and may play a crucial role
      as organ-specific autoantigens in the aetiopathogenesis of SjS. This study
      warranted clinical evaluations of autoantibodies against IFI16, KLHL12 and KLHL7
      in combination with anti-SS-B/La autoantibodies.

PMID- 16108818
TI  - Mechanism of up-regulation of immunoglobulin A production in the intestine of
      mice unresponsive to lipopolysaccharide.
AB  - The mechanisms by which immunoglobulin A (IgA) production up-regulates in the
      intestine of Toll-like receptor-4 (TLR4)-mutated mice were investigated. When
      TLR4-mutated, C3H/HeJ and BALB/lps(d) mice received oral administration of
      cholera toxin (CT), not only CT-specific IgA levels in the intestinal lavage but
      also the number of IgA-producing cells in intestinal lamina propria (iLP)
      significantly increased compared with those of the wild-type C3H/He and BALB/c
      mice. Interleukin (IL)-5-producing cells and CD86+ cells in iLP also
      significantly increased in C3H/HeJ mice. The expression of major
      histocompatibility complex class II and CD86 on cells present in Peyer's patches
      (PPs) of C3H/HeJ mice was higher than those of C3H/He mice. In non-immunized
      C3H/HeJ mice, the expression of transforming growth factor-beta (TGF-beta) mRNA
      and the percentages of IL-10-producing cells in PPs but not in spleen increased
      when compared with those in C3H/He mice. The suppressor of cytokine signalling-1
      (SOCS-1) was expressed in PPs of C3H/He mice but not C3H/HeJ mice. These results
      indicate that high IgA levels in the intestine of TLR4-mutated mice are due to up
      regulation of TGF-beta and IL-10 and the lack of regulation by SOCS-1.

PMID- 16108819
TI  - Formononetin, a phyto-oestrogen, and its metabolites up-regulate interleukin-4
      production in activated T cells via increased AP-1 DNA binding activity.
AB  - Phyto-oestrogens are polyphenolic non-steroidal plant compounds with oestrogen
      like biological activity. Phyto-oestrogens have many biological effects including
      oestrogen agonist/antagonist properties. However, the effect of phyto-oestrogens
      on allergic responses remains unclear. In this study we investigated whether
      formononetin, a phyto-oestrogen, and its metabolites, daidzein and equol, affect
      production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely
      associated with allergic immune response, in primary CD4+ T cells and EL4 T
      lymphoma cells. Formononetin, daidzein and equol significantly enhanced IL-4
      production from both CD4+ T cells and EL4 cells in a dose-dependent manner.
      Formononetin, daidzein and equol also enhanced IL-4 gene promoter activity in EL4
      cells transiently transfected with IL-4 gene promoter constructs, but this effect
      was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of
      P4 site carrying nuclear factor of activated T cells (NF-AT) and activator
      protein-1 (AP-1) binding sites. In addition, formononetin, daidzein and equol
      increased AP-1 DNA binding activities while did not affect NF-AT DNA binding
      activities. The enhancing effects on IL-4 production and AP-1 DNA binding
      activities were abrogated by specific inhibitors for phosphatidylinositol-3
      kinase (PI3K), protein kinase C (PKC) and p38 mitogen-activated protein kinase
      (MAPK), indicating that formononetin, daidzein and equol might enhance IL-4
      production by increased activation of AP-1 through the PI3-K/PKC/p38 MAPK
      signalling pathway. These results suggest that phyto-oestrogens and some of their
      metabolites may increase allergic responses via the enhancement of IL-4
      production in T cells.

PMID- 16108820
TI  - Expression of human pim family genes is selectively up-regulated by cytokines
      promoting T helper type 1, but not T helper type 2, cell differentiation.
AB  - Cytokines are the most important inducers of T helper (Th) cell differentiation.
      Interleukin-12 (IL-12) and interferon-alpha (IFN-alpha) are responsible for human
      Th1-cell differentiation, while IL-4 is the critical cytokine promoting Th2-cell
      development. These two subsets of cells co-ordinate immunological responses to
      pathogens as well as autoimmune or allergic reactions. The pim family of proto
      oncogenes encodes serine/threonine-specific kinases involved in cytokine-mediated
      signalling pathways in haematopoietic cells. Here we demonstrate that expression
      of pim-1 and pim-2 mRNAs is selectively up- or down-regulated in human cord-blood
      derived CD4+ cells freshly induced to polarize towards Th1 or Th2 cells,
      respectively, whereas their expression is inhibited in both cell types by the
      immunosuppressive transforming growth factor beta (TGF-beta). Moreover, the Th1
      specific cytokines IL-12 and IFN-alpha, but not the Th2-specific cytokine IL-4,
      transiently up-regulate pim-1 and pim-2 mRNA expression in human peripheral blood
      T cells and natural killer cells. In addition, the Pim-1 protein levels are
      strongly up-regulated by Th1-specific cytokines in all of these cell types. Taken
      together, our results suggest that pim genes and their protein products are
      involved in the early differentiation process of T helper cells.

PMID- 16108821
TI  - Identification of the V genes encoding xenoantibodies in non-immunosuppressed
      rhesus monkeys.
AB  - The major immunological barrier that prevents the use of wild-type pig xenografts
      as an alternative source of organs for human xenotransplantation is antibody
      mediated rejection. In this study, we identify the immunoglobulin variable region
      heavy (IgV(H)) chain genes encoding xenoantibodies to porcine heart and fetal
      porcine islet xenografts in non-immunosuppressed rhesus monkeys. We sought to
      compare the IgV(H) genes encoding xenoantibodies to porcine islets and solid
      organ xenografts. The immunoglobulin M (IgM) and IgG xenoantibody response was
      analysed by enzyme-linked immunosorbent assay and cDNA libraries from peripheral
      blood lymphocytes were prepared and sequenced. The relative frequency of IgV(H)
      gene usage was established by colony filter hybridization. Induced xenoantibodies
      were encoded by the IGHV3-11 germline progenitor, the same germline gene that
      encodes xenoantibodies in humans mounting active xenoantibody responses. The
      immune response to pig xenografts presented as solid organs or isolated cells is
      mediated by identical IgV(H) genes in rhesus monkeys. These animals represent a
      clinically relevant model to identify the immunological basis of pig-to-human
      xenograft rejection.

PMID- 16108822
TI  - Regulatory activity of human CD4 CD25 T cells depends on allergen concentration,
      type of allergen and atopy status of the donor.
AB  - Regulatory CD4+ CD25+ FoxP3-positive T cells (Treg) are functional in most atopic
      patients with allergic rhinitis and are able to inhibit T helper type 1 (Th1) and
      Th2 cytokine production of CD4+ CD25- T cells. This study was designed to analyse
      the following additional aspects: influence of allergen concentration, influence
      of the type of allergen, and influence of the atopy status of the donor on the
      strength of the regulatory activity. CD4+ CD25- T cells from healthy non-atopic
      controls or from grass-pollen-allergic or wasp-venom-allergic donors were
      stimulated alone or in the presence of Treg with autologous mature monocyte
      derived dendritic cells which were pulsed with different concentrations of the
      respective allergens. Treg from grass-pollen-allergic donors failed to inhibit
      proliferation but not cytokine production of CD4+ CD25- T cells at high antigen
      doses while Treg from non-atopic donors did not fail at these allergen
      concentrations. Proliferative responses and cytokine production of CD4+ CD25- T
      cells from most of the examined wasp-venom-allergic patients were not inhibited
      at any concentration of wasp venom. The use of wasp venom- or phospholipase A2
      pulsed dendritic cells for stimulation of CD4+ CD25- T cells from donors who were
      not allergic to wasp stings only resulted in an inhibited proliferation and Th2
      cytokine production by Treg at 10-fold lower than the optimal concentration,
      while interferon-gamma production was inhibited at all concentrations
      investigated. These data demonstrate that in allergic diseases the function of
      Treg is dependent on the concentration and the type of the respective allergen
      with different thresholds for individual allergens and patients.

PMID- 16108823
TI  - Dysregulated luminal bacterial antigen-specific T-cell responses and antigen
      presenting cell function in HLA-B27 transgenic rats with chronic colitis.
AB  - HLA-B27/beta2 microglobulin transgenic (TG) rats spontaneously develop T-cell
      mediated colitis when colonized with normal commensal bacteria, but remain
      disease-free under germ-free conditions. We investigated regulation of in vitro T
      cell responses to enteric bacterial components. Bacterial lysates prepared from
      the caecal contents of specific pathogen-free (SPF) rats stimulated interferon
      gamma (IFN-gamma) production by TG but not non-TG mesenteric lymph node (MLN)
      cells. In contrast, essentially equivalent amounts of interleukin-10 (IL-10) were
      produced by TG and non-TG cells. However, when cells from MLNs of non-TG rats
      were cocultured with TG MLN cells, no suppression of IFN-gamma production was
      noted. Both non-TG and TG antigen-presenting cells (APC) pulsed with caecal
      bacterial lysate were able to induce IFN-gamma production by TG CD4+ cells,
      although non-TG APC were more efficient than TG APC. Interestingly, the addition
      of exogenous IL-10 inhibited non-TG APC but not TG APC stimulation of IFN-gamma
      production by cocultured TG CD4+ lymphocytes. Conversely, in the presence of
      exogenous IFN-gamma, production of IL-10 was significantly lower in the
      supernatants of TG compared to non-TG APC cultures. We conclude that commensal
      luminal bacterial components induce exaggerated in vitro IFN-gamma responses in
      HLA-B27 TG T cells, which may in turn inhibit the production of regulatory
      molecules, such as IL-10. Alterations in the production of IFN-gamma, and in
      responses to this cytokine, as well as possible resistance of TG cells to
      suppressive regulation could together contribute to the development of chronic
      colitis in TG rats.

PMID- 16108824
TI  - Skin-derived dendritic cells acquire and degrade the scrapie agent following in
      vitro exposure.
AB  - The accumulation of the scrapie agent in lymphoid tissues following inoculation
      via the skin is critical for efficient neuroinvasion, but how the agent is
      initially transported from the skin to the draining lymph node is not known.
      Langerhans cells (LCs) are specialized antigen-presenting cells that continually
      sample their microenvironment within the epidermis and transport captured
      antigens to draining lymph nodes. We considered LCs probable candidates to
      acquire and transport the scrapie agent after inoculation via the skin. XS106
      cells are dendritic cells (DCs) isolated from mouse epidermis with
      characteristics of mature LC cells. To investigate the potential interaction of
      LCs with the scrapie agent XS106 cells were exposed to the scrapie agent in
      vitro. We show that XS106 cells rapidly acquire the scrapie agent following in
      vitro exposure. In addition, XS106 cells partially degrade the scrapie agent
      following extended cultivation. These data suggest that LCs might acquire and
      degrade the scrapie agent after inoculation via the skin, but data from
      additional experiments demonstrate that this ability could be lost in the
      presence of lipopolysaccharide or other immunostimulatory molecules. Our studies
      also imply that LCs would not undergo maturation following uptake of the scrapie
      agent in the skin, as the expression of surface antigens associated with LC
      maturation were unaltered following exposure. In conclusion, although LCs or DCs
      have the potential to acquire the scrapie agent within the epidermis our data
      suggest it is unlikely that they become activated and stimulated to transport the
      agent to the draining lymph node.

PMID- 16108826
TI  - Breast cancer resistance protein: molecular target for anticancer drug resistance
      and pharmacokinetics/pharmacodynamics.
AB  - Breast cancer resistance protein (BCRP) is a half-molecule ATP-binding cassette
      transporter that forms a functional homodimer and pumps out various anticancer
      agents, such as 7-ethyl-10-hydroxycamptothecin, topotecan, mitoxantrone and
      flavopiridol, from cells. Estrogens, such as estrone and 17beta-estradiol, have
      been found to restore drug sensitivity levels in BCRP-transduced cells by
      increasing the cellular accumulation of such agents. Furthermore, synthetic
      estrogens, tamoxifen derivatives and phytoestrogens/flavonoids have now been
      identified that can effectively circumvent BCRP-mediated drug resistance.
      Transcellular transport experiments have shown that BCRP transports sulfated
      estrogens and various sulfated steroidal compounds, but not free estrogens. The
      kinase inhibitor gefitinib inhibited the transporter function of BCRP and
      reversed BCRP-mediated drug resistance both in vitro and in vivo. BCRP-transduced
      human epidermoid carcinoma A431 (A431/BCRP) and BCRP-transduced human non-small
      cell lung cancer PC-9 (PC-9/BCRP) cells showed gefitinib resistance.
      Physiological concentrations of estrogens (10-100 pM) reduced BCRP protein
      expression without affecting its mRNA levels. Two functional polymorphisms of the
      BCRP gene have been identified. The C376T (Q126Stop) polymorphism has a dramatic
      phenotype as active BCRP protein cannot be expressed from a C376T allele. The
      C421A (Q141K) polymorphism is also significant as Q141K-BCRP-transfected cells
      show markedly low protein expression levels and low-level drug resistance. Hence,
      individuals with C376T or C421A polymorphisms may express low levels of BCRP or
      none at all, resulting in hypersensitivity of normal cells to BCRP-substrate
      anticancer agents. In summary, both modulators of BCRP and functional single
      nucleotide polymorphisms within the BCRP gene affect the transporter function of
      the protein and thus can modulate drug sensitivity and substrate pharmacokinetics
      and pharmacodynamics in affected cells and individuals.

PMID- 16108825
TI  - Circulating and thymic CD4 CD25 T regulatory cells in myasthenia gravis: effect
      of immunosuppressive treatment.
AB  - Accumulating evidence indicates an immunosuppressive role of the thymus-derived
      CD4+ T-cell population constitutively expressing high level of CD25, T regulatory
      (Treg) cells, in autoimmune diseases. Here we show that the number of Treg cells
      in the blood is significantly lower in untreated myasthenia gravis patients than
      in age-matched healthy subjects, whereas it is normal or elevated in patients on
      immunosuppressive therapy (prednisone frequently associated with azathioprine).
      Therapeutic thymectomy (Tx) for either the thymoma or non-neoplastic thymic
      alterations that are often associated with myasthenia gravis provided unique
      material for studying intrathymic Treg cells and correlating them with their
      peripheral counterparts. We observed that Tx prevents the increase of Treg cells
      in the circulation that follows immunosuppressive therapy (particularly evident
      if the thymus is not neoplastic), indicating that the thymus contributes to Treg
      cell normalization. However, thymic Treg cells are not modulated by
      immunosuppressive therapy and even in thymectomized patients Treg-cell numbers in
      the blood eventually recover. The present findings suggest that a deficiency in
      Treg cells favours the development of myasthenia gravis and that their
      normalization is an important clinical benefit of immunosuppressive therapy. Treg
      normalization appears to be largely thymus independent and possibly reflects the
      reported capacity of corticosteroids to promote Treg-cell development.

PMID- 16108827
TI  - Hodgkin's lymphoma cells are efficiently engrafted and tumor marker CD30 is
      expressed with constitutive nuclear factor-kappaB activity in unconditioned
      NOD/SCID/gammac(null) mice.
AB  - As there are very few reproducible animal models without conditioning available
      for the study of human B-cell-type Hodgkin's lymphoma (HL), we investigated the
      ability of HL cells to induce tumors using novel NOD/SCID/gammac(null) (NOG)
      mice. Four human Epstein-Barr virus-negative cell lines (KM-H2 and L428
      originated from B cells, L540 and HDLM2 originated from T cells) were inoculated
      either subcutaneously in the postauricular region or intravenously in the tail of
      unmanipulated NOG mice. All cell lines successfully engrafted and produced tumors
      with infiltration of cells in various organs of all mice. Tumor cells had
      classical histomorphology as well as expression patterns of the tumor marker
      CD30, which is a cell surface antigen expressed on HL. Tumor progression in mice
      inoculated with B-cell-type, but not T-cell-type, HL cells correlated with an
      elevation in serum human interleukin-6 levels. Tumor cells from the mice also
      retained strong nuclear factor (NF)-kappaB DNA binding activity, and the induced
      NF-kappaB components were indistinguishable from those cultured in vitro. The
      reproducible growth behavior and preservation of characteristic features of both
      B-cell-type and T-cell-type HL in the mice suggest that this new xenotransplant
      model can provide a unique opportunity to understand and investigate the
      mechanism of pathogenesis and malignant cell growth, and to develop novel
      anticancer therapies.

PMID- 16108828
TI  - DNA methylation profiles of differentiated-type gastric carcinomas with distinct
      mucin phenotypes.
AB  - Gastric carcinomas (GC) are classified into four phenotypes according to mucin
      expression. Previous studies revealed the association of distinct genetic
      profiles in GC with mucin phenotypic expression; however, the roles of epigenetic
      changes, such as DNA methylation, are poorly understood. We examined whether the
      phenotypic expression of GC was associated with DNA methylation of hMLH1, MGMT,
      p16(INK4a), RAR-beta or CDH1. Expression of HGM, M-GGMC-1, MUC2, and CD10 was
      analyzed immunohistochemically in 33 advanced GC with differentiated histology.
      HGM was expressed in 14 (42.4%) cases, M-GGMC-1 in five (15.2%) cases, MUC2 in 15
      (45.5%) cases and CD10 in 18 (54.5%) cases. DNA methylation was detected in five
      (15.2%) cases for hMLH1, 11 (33.3%) cases for MGMT, 13 (39.4%) cases for
      p16(INK4a), 17 (51.5%) cases for RAR-beta and 14 (42.4%) cases for CDH1 by
      bisulfite-polymerase chain reaction and methylation-specific polymerase chain
      reaction. DNA methylation of hMLH1 occurred more frequently in MUC2-negative GC
      than in MUC2-positive GC (P = 0.0488, Fisher's exact test). In contrast, MGMT was
      more frequently methylated in MUC2-positive GC than in MUC2-negative GC (P =
      0.0078, Fisher's exact test). There was no correlation between gastric or
      intestinal-markers and methylation of the p16(INK4a), RAR-beta and CDH1 genes.
      These results indicate that DNA methylation of specific genes, such as hMLH1 and
      MGMT, may be involved partly in the distinct phenotypic expression of GC.

PMID- 16108829
TI  - Loss of TSLC1 expression in lung adenocarcinoma: relationships with histological
      subtypes, sex and prognostic significance.
AB  - The TSLC1 (tumor suppressor in lung cancer 1) gene is a tumor suppressor recently
      identified through functional complementation in a lung adenocarcinoma cell line
      A549. In this study we immunohistochemically examined the loss of TSLC1
      expression in 93 cases of surgically resected lung adenocarcinoma, and
      investigated its correlation with clinicopathological parameters, including
      histological subtypes of tumors. The prognostic significance of loss of TSLC1
      expression was analyzed by univariate and multivariate analyses, in parallel with
      other prognostic markers such as p53, p27, and Ki-67. In non-cancerous lung
      tissue, TSLC1 was weakly positive in bronchial and bronchiolar epithelial cells,
      type II pneumocytes and bronchial glands. Overall, TSLC1 was negative in 60 of 93
      lung adenocarcinomas. TSLC1 was mainly localized in the cytoplasm of the cells,
      but cell membrane staining was also observed, especially at sites of cell-cell
      adhesion. TSLC1-negative tumors were more frequently observed in male cases
      (41/54 cases, 70.0%) than in female cases (19/39 cases, 48.7%) (P < 0.01).
      Notably, TSLC1 expression was preserved in a non-invasive, bronchiolo-alveolar
      histological pattern of tumor cells (P < 0.0001). Survival analyses showed that
      loss of TSLC1 expression was associated with lower patient survival in univariate
      and multivariate analyses (P < 0.05 and P = 0.059, respectively). Subset analyses
      further showed that the prognostic impact of loss of TSLC1 was significant for
      male patients (P = 0.0089), but not for female patients. We conclude that TSLC1
      is expressed in a subset of lung adenocarcinomas, especially in those with
      bronchiolo-alveolar spread pattern. Loss of TSLC1 is associated with lower
      patient survival, supporting its role as a tumor suppressor.

PMID- 16108830
TI  - Stimulation of CD30 in anaplastic large cell lymphoma leads to production of
      nuclear factor-kappaB p52, which is associated with hyperphosphorylated Bcl-3.
AB  - Anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL) express CD30 at
      high levels, but stimulation of this molecule has been reported to induce
      contradictory effects. To elucidate the molecular mechanism of CD30-mediated
      apoptosis of ALCL, we compared the gene expression profiles of t(2;5)(p23;q35)
      positive ALCL with those of HL altered by CD30 agonistic stimulation. The results
      showed that BCL3, the high-level expression of which in ALCL was previously
      reported, was further upregulated in response to CD30 stimulation, along with
      several pro-apoptotic genes. Bcl-3 protein was present as an intermediate phospho
      form in the resting-state ALCL, becoming hyperphosphorylated (Bcl-3P) upon
      stimulation. We next found that the stimulation promoted de novo synthesis of the
      nuclear factor (NF)-kappaB2/p100 precursor as well as processing to p52, and a
      series of immunoprecipitation and western blotting analyses consistently showed
      association of Bcl-3P with p52 in CD30-stimulated ALCL. An electrophoretic
      mobility shift assay revealed the induction of kappaB binding activity of the p52
      homodimer, and nuclear colocalization of Bcl-3 and p52 was demonstrated in
      anaplastic lymphoma kinase-positive ALCL tumor tissues by immunohistochemistry.
      As Bcl-3 can act as an anti-repressor or transactivator or both, we propose that
      the (p52)2/Bcl-3P ternary complex, which is specifically induced in CD30
      stimulated ALCL, can modulate expression of apoptosis-related genes regulated by
      NF-kappaB, thereby accounting for CD30-mediated apoptosis of ALCL.

PMID- 16108831
TI  - Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for
      cancer immunotherapy of gastrointestinal and hepatocellular carcinomas.
AB  - We previously performed gene expression profile analyses of 20 intestinal-type
      gastric cancers, and identified a set of genes whose expression levels were
      elevated in cancer tissues compared to their corresponding non-cancerous tissues.
      In the present study we focused on the immunoglobulin superfamily 11 gene
      (IGSF11). Its expression was also elevated in colorectal cancers and
      hepatocellular carcinomas as well as intestinal-type gastric cancers. Northern
      blot analysis showed that it was expressed abundantly in testis and ovary. These
      data suggest that IGSF11 is a good candidate of cancer-testis antigen.
      Furthermore, suppression of IGSF11 by siRNA retarded the growth of gastric cancer
      cells. To investigate the possibility of clinical application of peptide vaccine
      to IGSF11, we synthesized candidate epitope peptides for IGSF11 and tested
      whether the peptides elicit IGSF11-specific CTL. As a result, we successfully
      established oligo-clonal CTL by stimulation with IGSF11-9-207 (ALSSGLYQC). In
      addition, we also established additional CTL using IGSF11-9V (ALSSGLYQV), anchor
      modified peptides of IGSF11-9-207. These peptides showed IGSF11-specific
      cytotoxic activity in an HLA-A*0201-restricted fashion, suggesting that these
      peptides may be applicable for cancer immunotherapy. These findings have provided
      a novel insight into carcinogenesis of the stomach, colon and liver, and will be
      helpful for the development of novel therapeutic strategies to a wide range of
      human cancers.

PMID- 16108832
TI  - Influence of the C161T but not Pro12Ala polymorphism in the peroxisome
      proliferator-activated receptor-gamma on colorectal cancer in an Indian
      population.
AB  - The aim of the present study was to investigate associations between Pro12Ala and
      C161T polymorphisms in the peroxisome proliferator-activated receptor-gamma (PPAR
      gamma) gene and colorectal cancer (CRC) risk. We recruited 301 newly diagnosed
      CRC patients and 291 healthy control subjects at the Madras Cancer Institute in
      Chennai, India, from 1999 to 2001. Genotypes of the Pro12Ala and C161T
      polymorphisms were determined using the PCR-RFLP method. After adjustment for
      age, sex, smoking habit, family history and family income, an increased risk of
      CRC was observed for the C/T + T/T genotype compared to the C/C genotype of the
      C161T polymorphism (odds ratio = 1.61, 95% confidence interval: 1.10-2.36),
      whereas no significant association was found for Pro12Ala (odds ratio = 1.06, 95%
      confidence interval: 0.70-1.61). Analysis with estimated haplotypes showed a
      significant difference in haplotype frequencies between cases and controls
      (chi(2) = 11.62, P = 0.009, d.f. = 3). The relationship between the two
      polymorphisms and CRC risk was not significantly modified by dietary intake of
      fish. Although the biological mechanisms of the observed association remain to be
      elucidated, our findings suggest that the C161T polymorphism of the PPAR-gamma
      gene is related to risk of CRC. Further research is needed to investigate
      functional implications of polymorphisms of the PPAR-gamma gene in CRC
      development.

PMID- 16108833
TI  - Genetic polymorphisms of methylenetetrahydrofolate reductase and aldehyde
      dehydrogenase 2, alcohol use and risk of colorectal adenomas: Self-Defense Forces
      Health Study.
AB  - Methylenetetrahydrofolate reductase is a key enzyme in folate metabolism, which
      affects DNA synthesis and methylation and is possibly linked to colorectal
      carcinogenesis. Alcohol and acetaldehyde have an adverse effect on folate
      metabolism. This study investigated the relationship of functional MTHFR C677T
      and ALDH2 polymorphisms to colorectal adenomas with reference to alcohol
      consumption in a case-control study of male officials in the Self-Defense Forces
      (SDF) who received a preretirement health examination at two SDF hospitals. The
      study subjects were 452 cases of colorectal adenoma and 1050 controls with no
      polyp who underwent total colonoscopy. Genotypes were determined by the PCR-RFLP
      method using genomic DNA extracted from the buffy coat. Statistical adjustment
      was made for age, hospital, rank in the SDF, body mass index, cigarette-years and
      alcohol intake. Neither MTHFR C677T nor ALDH2 showed a measurable association
      with colorectal adenoma. While high alcohol consumption was associated with a
      moderately increased risk of colorectal adenoma, neither of the two polymorphisms
      showed a significant effect on the association between alcohol and colorectal
      adenoma. Individuals with the variant alleles ALDH2*2 and MTHFR 677T had a
      decreased risk of colorectal adenomas, showing adjusted odds ratios of 0.70 (95%
      confidence interval 0.49-1.00) for all adenomas and 0.57 (0.34-0.95) for large
      adenomas (> or = 5 mm), as compared to individuals with ALDH2*1/1 and MTHFR 677CC
      genotypes combined. The findings may be interpreted as suggesting that folate
      inhibits the growth of colorectal adenomas, but further confirmation is needed.

PMID- 16108834
TI  - Enhanced T-cell response to mosquito extracts by NK cells in hypersensitivity to
      mosquito bites associated with EBV infection and NK cell lymphocytosis.
AB  - Hypersensitivity to mosquito bites is characterized by severe systemic as well as
      local symptoms, and associated with chronic active EBV infection and NK cell
      lymphocytosis. In this HEN disease, we investigated the response of PBMC to MSG
      extracts. PBMC were taken from three defined cases of HEN disease, three
      borderline cases, five individuals with simple exaggerated reactions to mosquito
      bites without systemic symptoms (simple responders), and eight healthy donors.
      PBMC, or purified CD4+, CD8+ or CD56+ cells, were cultured with MSG extracts
      prepared from each of five mosquito species to examine their proliferation and
      cytokine secretion. The patients with HEN disease had high stimulation indices
      with variations in responses to the extracts from Aedes albopictus, Aedes
      aegypti, Anopheles sinensis and Culex pipiens pallens. However, a non-Japan
      habitant species Anopheles stephensi did not stimulate the patients' PBMC. Some
      borderline or simple responders showed moderate proliferation, and healthy donors
      had no reactive PBMC. In HEN disease, both CD56+ NK cells (producing IFN-gamma)
      and CD4+ Th0 cells (producing IL-4 and IFN-gamma) were increased in the blood.
      CD4+ cells, but not CD56+ NK cells or CD8+ cells, propagated in response to MSG
      extracts. However, this response of CD4+ cells and their IL-4 production were
      strongly enhanced by coexisting CD56+ cells. We suggest that the CD4+ T cell
      serving as the primary responder to MSG antigen and the NK cell functioning as
      the enhancer are both pathogenic in the development of HMB.

PMID- 16108835
TI  - Possible origin of adult T-cell leukemia/lymphoma cells from human T lymphotropic
      virus type-1-infected regulatory T cells.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disorder caused by
      human T lymphotropic virus type 1 (HTLV-I). Although ATLL cells display an
      activated helper/inducer T-cell phenotype, CD4+ and CD25+, they are known to
      exhibit strong immunosuppressive activity. As regulatory T cells (Treg cells)
      express CD4+ and CD25+ molecules and possess potent immune response suppressive
      activity, we investigated a possible link between ATLL cells and Treg cells. In
      primary ATLL cells, the expression levels of the Treg cell marker molecules Foxp3
      and glucocorticoid-induced tumor necrosis factor receptor family related protein
      (GITR) were significantly higher than in those from healthy adults. Furthermore,
      ATLL cells are unresponsive in vitro to concanavalin A stimulation and suppress
      the proliferation of normal T cells. GITR mRNA expression was induced by the HTLV
      I transactivator Tax, and GITR promoter analyses revealed that this induction
      depends on the kappaB site from -431 bp to -444 bp upstream of the putative
      transcription site. Taken together, ATLL cells may originate from HTLV-I-infected
      Treg cells, and GITR seems to be involved in the progression to ATLL.

PMID- 16108837
TI  - Recent concepts in non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is present in up to one-third of the
      general population and in the majority of patients with metabolic risk factors
      such as obesity and diabetes. Insulin resistance is a key pathogenic factor
      resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn
      exacerbates hepatic insulin resistance and often precedes glucose intolerance.
      Once hepatic steatosis is established, other factors, including oxidative stress,
      mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may
      promote hepatocellular damage, inflammation and progressive liver disease.
      Confirmation of the diagnosis of NAFLD can usually be achieved by imaging
      studies, however, staging the disease requires a liver biopsy. NAFLD is
      associated with an increased risk of all-cause death, probably because of
      complications of insulin resistance such as vascular disease, as well as
      cirrhosis and hepatocellular carcinoma, which occur in a minority of patients.
      NAFLD is also now recognized to account for a substantial proportion of patients
      previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the
      necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk
      factors for progressive liver disease. Current treatment relies on weight loss
      and exercise, although various insulin-sensitizing medications appear promising.
      Further research is needed to identify which patients will achieve the most
      benefit from therapy.

PMID- 16108838
TI  - Serum gamma-glutamyltransferase within its normal concentration range is related
      to the presence of diabetes and cardiovascular risk factors.
AB  - AIMS: Although many studies have reported an association between serum gamma
      glutamyltransferase (GGT) and cardiovascular risk factors, the mechanism of this
      relationship has not been clarified. METHODS: The medical records of 29,959
      subjects (age, median 48, range 14-90 years; 16,706 men, 13,253 women) who
      visited the Center for Health Promotion at Samsung Medical Center for a medical
      check-up between January 2001 and December 2003, were investigated. Subjects with
      hepatic enzyme/GGT concentrations higher than three times the upper limit of the
      reference range, a positive test for hepatitis C virus antibody, a positive test
      for hepatitis B virus surface antigen, currently taking anti-diabetic/anti
      hypertensive/anti-lipid medication, or a white blood cell (WBC) count higher than
      10,000 cells/ml, were excluded. The subjects of each gender were classified into
      five groups according to their serum GGT concentrations, into quartiles of the
      normal range of GGT (groups 1, 2, 3 and 4) and into a group with elevated GGT
      (group 5). RESULTS: As the group number increased (group 1 --> 5), the
      frequencies of all of the following increased: (i) diabetes and impaired fasting
      glucose (IFG); (ii) hypertension, obesity (body mass index > or = 27 kg/m2),
      dyslipidaemia (LDL-cholesterol > or = 4.1 mmol/l and/or triglyceride > or = 2.46
      mmol/l, or HDL-cholesterol < 1.16 mmol/l); (iii) metabolic syndrome. Moreover,
      these significant relationships between GGT concentrations within its normal
      range and the presence of diabetes/IFG, hypertension, obesity, dyslipidaemia, and
      metabolic syndrome persisted after adjusting for several clinical and biochemical
      variables and for the presence of fatty liver based on ultrasonographic findings.
      Odds ratios (95% CI) for group 4 (highest quartile of normal range of GGT) vs.
      group 1 (lowest quartile of normal range of GGT); the referent group, were 3.16
      (2.15-4.65) for diabetes, 2.24 (1.73-2.90) for IFG, 1.93 (1.59-2.33) for obesity,
      1.38 (1.23-1.55) for dyslipidaemia and 2.88 (2.28-3.65) for metabolic syndrome in
      men. In women, the odds ratios were 2.72 (1.34-5.52), 3.67 (2.26-5.97), 2.10
      (1.61-2.74), 1.80 (1.58-2.04) and 3.57 (2.52-5.07), respectively. CONCLUSIONS:
      Our data show that, even within its normal range, serum GGT concentrations are
      closely associated with the presence of diabetes and cardiovascular risk factors,
      and that these associations are independent of a fatty liver by ultrasonography.

PMID- 16108839
TI  - Prevalence of non-alcoholic fatty liver disease and its association with impaired
      glucose metabolism in Japanese adults.
AB  - AIMS: To assess the prevalence of non-alcoholic fatty liver disease (NAFLD) and
      its association with impaired glucose metabolism in Japanese subjects. METHODS:
      One thousand, nine hundred and fifty subjects enrolled in a general health
      examination programme from September 2002 to February 2003 were recruited. NAFLD
      was diagnosed if a person showed 'fatty liver' on ultrasonography, and his/her
      alcohol consumption, estimated by questionnaire, was < 40 gram/week. A general
      linear model was used for the comparison of estimated means of metabolic
      variables adjusted for age and body mass index (BMI) between subjects with NAFLD
      and those without fatty liver. Multivariate regression with fasting plasma
      glucose (FPG) as the dependent variable was performed in 1547 non-diabetic
      individuals after adjusting for age, gender, BMI and NAFLD. RESULTS: NAFLD was
      found in 566 of the 1950 health-check examinees (29%). Its prevalence increased
      with increasing FPG levels: 27% in the subgroup with normal fasting glucose, 43%
      in impaired fasting glucose and 62% in newly diagnosed diabetes. Adjusted means
      of FPG, HbA1c, triglyceride, total protein, albumin, AST and ALT were all
      significantly higher, while adjusted means of HDL cholesterol and AST/ALT ratio
      were significantly lower in subjects with NAFLD than those without fatty liver.
      Multivariate regression analysis showed that NAFLD was independently associated
      with increasing FPG in non-diabetic individuals. CONCLUSIONS: The prevalence of
      NAFLD was 29% in apparently healthy middle-aged Japanese adults and NAFLD was
      independently associated with impaired glucose metabolism.

PMID- 16108840
TI  - Relationship of non-alcoholic hepatic steatosis to cortisol secretion in diet
      controlled Type 2 diabetic patients.
AB  - AIMS: To examine the association of non-alcoholic hepatic steatosis (HS) with the
      activity of the hypothalamo-pituitary-adrenal (HPA) axis in Type 2 diabetic
      individuals. METHODS: The activity of the HPA axis, as measured by 24-h urinary
      free cortisol (UFC) excretion and serum cortisol levels after 1.0 mg
      dexamethasone, was measured in 40 diet-controlled, predominantly overweight, Type
      2 diabetic patients with non-alcoholic HS and in 40 diabetic patients without HS
      who were comparable for age, sex and body mass index (BMI). RESULTS: Subjects
      with non-alcoholic HS had significantly higher 24-h UFC excretion (191 +/- 4 vs.
      102 +/- 3 nmol/24 h; P < 0.001) and post-dexamethasone cortisol concentrations
      (29.1 +/- 2 vs. 14.4 +/- 1 nmol/l; P < 0.001) than those without HS. Patients
      with HS had significantly higher values for HOMA insulin resistance score, plasma
      triglycerides and liver enzymes. Age, sex, BMI, waist-hip ratio (WHR), diabetes
      duration, HbA1c, LDL-cholesterol and blood pressure values were not different
      between the groups. The differences in urinary and serum cortisol concentrations
      between the groups remained significant after adjustment for age, sex, BMI, WHR,
      HOMA insulin resistance score, plasma triglycerides, HbA1c and liver enzymes. In
      multiple logistic regression analyses, 24-h UFC or serum cortisol concentrations
      (P < 0.05 and P = 0.02, respectively), along with age and HOMA insulin
      resistance, predicted the presence of HS, independently of potential confounders.
      CONCLUSIONS: These results demonstrate that non-alcoholic HS is closely
      associated with a subtle, chronic overactivity of the HPA axis in diet-controlled
      Type 2 diabetic individuals.

PMID- 16108841
TI  - Telomere shortening occurs in Asian Indian Type 2 diabetic patients.
AB  - AIM: Telomere shortening has been reported in several diseases including
      atherosclerosis and Type 1 diabetes. Asian Indians have an increased predilection
      for Type 2 diabetes and premature coronary artery disease. The aim of this study
      was to determine whether telomeric shortening occurs in Asian Indian Type 2
      diabetic patients. METHODS: Using Southern-blot analysis we determined mean
      terminal restriction fragment (TRF) length, a measure of average telomere size,
      in leucocyte DNA. Type 2 diabetic patients without any diabetes-related
      complications (n = 40) and age- and sex-matched control non-diabetic subjects (n
      = 40) were selected from the Chennai Urban Rural Epidemiology Study (CURES).
      Plasma level of malondialdehyde (MDA), a marker of lipid peroxidation, was
      measured by TBARS (thiobarbituric acid reactive substances) using a fluorescence
      method. RESULTS: Mean (+/- SE) TRF lengths of the Type 2 diabetic patients (6.01
      +/- 0.2 kb) were significantly shorter than those of the control subjects (9.11
      +/- 0.6 kb) (P = 0.0001). Among the biochemical parameters, only levels of TBARS
      showed a negative correlation with shortened telomeres in the diabetic subjects
      (r = -0.36; P = 0.02). However, telomere lengths were negatively correlated with
      insulin resistance (HOMA-IR) (r = -0.4; P = 0.01) and age (r = -0.3; P = 0.058)
      and positively correlated with HDL levels (r = 0.4; P = 0.01) in the control
      subjects. Multiple linear regression (MLR) analysis revealed diabetes to be
      significantly (P < 0.0001) associated with shortening of TRF lengths.
      CONCLUSIONS: Telomere shortening occurs in Asian Indian Type 2 diabetic patients.

PMID- 16108842
TI  - Large-scale studies of the Leu72Met polymorphism of the ghrelin gene in relation
      to the metabolic syndrome and associated quantitative traits.
AB  - AIM: Recently, low-frequency polymorphisms in the coding region of the ghrelin
      gene were suggested to be involved in the aetiology of obesity and to modulate
      glucose-induced insulin secretion in different ethnic study groups. The objective
      of the present large study was to investigate whether the Leu72Met polymorphism
      of the ghrelin gene associates with features of the metabolic syndrome (MS) in
      the Danish population. METHODS: The variant was examined, using PCR-RFLP, in the
      DanMONICA cohort, a population-based sample of 2413 subjects. The metabolic
      syndrome was defined using the National Cholesterol Education Program-Adult
      Treatment Panel III (NCEP-ATPIII) criteria. RESULTS: The allelic frequency of the
      Met72 allele was 8.6%[6.3-10.9%] in the MS group and 7.8%[7.0-8.6%] among
      subjects classified as not having the MS (NS). Similarly, there were no
      significant differences across the three groups of genotypes with respect to any
      of the examined variables, including BMI, waist circumference, fasting serum
      lipids, plasma glucose, serum insulin and HOMA estimates of insulin resistance
      and insulin secretion. CONCLUSION: In conclusion, the Leu72Met polymorphism of
      the ghrelin gene is not associated with the metabolic syndrome or related
      quantitative traits in the Danish population.

PMID- 16108843
TI  - Genetic polymorphisms in peroxisome proliferator-activated receptor gamma are
      associated with Type 2 diabetes mellitus and obesity in the Korean population.
AB  - AIMS: We examined whether the common polymorphisms of the peroxisome proliferator
      activated receptor-gamma (PPARgamma) gene are associated with Type 2 diabetes or
      obesity in the Korean population. METHODS: We genotyped two common PPARgamma
      polymorphisms (Pro12Ala and 161C > T) and examined their association with the
      clinical phenotypes found in 684 patients with Type 2 diabetes mellitus and 291
      non-diabetic control subjects. RESULTS: The 12Ala allele was less frequent in the
      Type 2 diabetic patients than in the non-diabetic control subjects (0.036 vs.
      0.053, P = 0.024). The allele frequencies of the 161C > T polymorphism did not
      differ between the control and Type 2 diabetic group (0.158 vs. 0.173). In the
      non-diabetic controls, those with the T allele had lower BMI and fasting serum
      triglyceride (TG) concentrations than those with the C/C homozygote (22.7 +/- 2.9
      vs. 23.8 +/- 3.2 kg/m2, P = 0.002; 1.45 +/- 0.81 vs. 1.65 +/- 0.83 mmol/l, P =
      0.03, respectively). The 12Ala-161T haplotype was associated with a decreased
      risk for Type 2 diabetes (OR = 0.47, P = 0.009), whereas the 12Pro-161T haplotype
      was associated with lower BMI and lower fasting serum TG (22.5 +/- 2.8 vs. 23.7
      +/- 3.2 kg/m2, P = 0.004; 1.41 +/- 0.87 vs. 1.64 +/- 0.79 mmol/l, P = 0.02,
      respectively). CONCLUSIONS: The PPARgamma 12Ala allele was associated with a
      reduced risk of Type 2 diabetes, whereas the PPARgamma 161T allele was associated
      with lower BMI and fasting serum TG concentrations in the Korean subjects. The
      subjects with 12Ala-161T haplotypes had a reduced risk of Type 2 diabetes.

PMID- 16108844
TI  - The presence of allele D of angiotensin-converting enzyme polymorphism is
      associated with diabetic nephropathy in patients with less than 10 years duration
      of Type 2 diabetes.
AB  - AIM: To investigate the association between angiotensin-converting enzyme gene
      I/D polymorphism and diabetic nephropathy (DN) in patients with Type 2 diabetes
      mellitus (DM) taking into consideration the known duration of DM. METHODS: Cross
      sectional study with 982 patients categorized according to urinary albumin
      excretion (UAE) into normoalbuminuria (UAE < 20 microg/min or < 17 mg/l, 24-h
      timed urine or spot random sterile urine, respectively), incipient DN (UAE 20-199
      microg/min or 17-174 mg/l) and overt DN (UAE > 200 microg/min or > 174 mg/l or
      dialysis). Patients were further grouped regarding presence of the D allele
      (DD/ID vs. II) and DM duration (< or = 10 years or > 10 years). RESULTS:
      Incipient DN was diagnosed in 17.3% (n = 170), and 20.7% (n = 203) had overt DN
      (macroalbuminuria, n = 129; dialysis, n = 74). Genotype distribution (DD/ID/II)
      was similar in patients with incipient (49/92/29) or overt DN (77/89/37) if
      compared with patients without DN (181/308/120, P = 0.172). In patients with DM <
      or = 10 years, having the D allele (DD/ID) resulted in an odds ratio (OR) of 2.66
      (95% CI: 1.12-6.58, P = 0.015) for incipient DN, and 3.19 (95% CI: 1.18-9.30, P =
      0.012) for overt DN. In patients with longer DM duration, the D allele did not
      increase the risk for incipient (OR 0.68, 95% CI 0.36-1.29, P = 0.206) or overt
      DN (OR 0.67, 95% CI 0.39-1.17, P = 0.138). CONCLUSION: The DD/ID genotypes were
      associated with incipient or overt DN in patients with DM < or = 10 years.

PMID- 16108845
TI  - The comparison of venous plasma glucose and whole blood capillary glucose in
      diagnoses of Type 2 diabetes: a population-based screening study.
AB  - AIM: To evaluate the degree of concordance between venous plasma glucose (PG) and
      capillary whole blood glucose (BG) in diagnosing Type 2 diabetes and to compare
      the prevalence of confirmed and unconfirmed Type 2 diabetes. METHODS: All 40- to
      69-year olds without known diabetes listed with five general practices were
      invited for screening (2051 persons). People identified by screening as being at
      high risk for having diabetes (random BG (rBG) > or = 4.5 mmol/l or HbA1c > or =
      5.9%) were examined using BG and PG. The main outcome measures were confirmed
      diabetes cases (one diabetic glucose value plus symptoms or two diabetic glucose
      values on two different days) and unconfirmed diabetes (one diabetic glucose
      value on the first day of testing). RESULTS: One thousand and twenty-eight (50%)
      accepted screening. Diabetes was confirmed by BG or PG in 22 patients (1.8%), and
      in 14 of these by both BG and PG. Four patients in whom diabetes was confirmed
      only by BG had unconfirmed diabetes by PG. Three of four people in whom diabetes
      was confirmed only by PG had unconfirmed diabetes according to BG. The prevalence
      of unconfirmed diabetes was 3.3% and the prevalence of confirmed diabetes 2.1%.
      CONCLUSION: Confirmed diabetes can be diagnosed by either BG or PG. BG seems more
      convenient than PG for use in general practice. The prevalence of confirmed
      diabetes was lower than the prevalence of unconfirmed diabetes.

PMID- 16108846
TI  - Hyperproinsulinaemia and risk of Type 2 diabetes mellitus in women.
AB  - AIMS: Our objective was to examine prospectively the associations between fasting
      plasma proinsulin and the proinsulin/insulin ratio and the incidence of Type 2
      diabetes in women. SUBJECTS AND METHODS: We designed a nested case-control study
      within the Nurses' Health Study, a cohort of 121,700 US women aged 30-55 years at
      study inception in 1976. Fasting plasma proinsulin, specific insulin and C
      peptide levels were determined in 183 women with a new diagnosis of diabetes made
      after blood sampling between 1989 and 1990, and 369 control subjects without
      diabetes. RESULTS: After adjustment for age, body mass index, family history of
      diabetes and other potential confounders, including HbA1c, the odds ratios for
      diabetes associated with increasing quartiles of proinsulin were 1.00, 0.85, 2.49
      and 5.73 (P for trend: < 0.001). Proinsulin remained significantly associated
      with diabetes risk after adjusting for C-peptide and specific insulin
      (multivariate odds ratios for quartiles: 1.00, 0.78, 1.94, 3.69; P for trend =
      0.001). In addition, the proinsulin/insulin ratio was significantly associated
      with diabetes risk, controlling in multivariate analysis for C-peptide (odds
      ratios for extreme quartiles: 2.48; 95% CI: 1.14-5.41; P for trend = 0.005).
      CONCLUSIONS: These data suggest that proinsulin and the proinsulin/insulin ratio
      are strong independent predictors of diabetes risk, after adjustment for obesity
      and other potential confounders.

PMID- 16108847
TI  - Plasma nitrotyrosine levels, antioxidant vitamins and hyperglycaemia.
AB  - AIMS: Studies on plasma nitrotyrosine (NT) levels, a measure of oxidative injury,
      in diabetes are limited and discordant; the amount of antioxidants might
      represent a possible explanation for the discordant results. The aim of this
      paper is to evaluate the association between plasma NT levels and glucose
      tolerance status, according to antioxidant vitamin intakes. METHODS: In three
      hundred men randomly selected from a population-based cohort, NT levels were
      measured and dietary intake assessed by a food-frequency questionnaire. Results
      NT values were similar in patients with diabetes (n = 34), impaired fasting
      glucose (n = 77) and normoglycaemic subjects (n = 189). However, in subjects with
      lower than recommended daily intakes of antioxidant vitamins C and A, NT levels
      were significantly higher in the diabetic patients. In a multiple regression
      model, after adjustments for age, body mass index (BMI) and smoking habits, NT
      levels were significantly associated with fasting glucose in patients with lower
      intakes of vitamin C (beta = 11.4; 95% CI 1.3-21.5) and vitamin A (beta = 14.9;
      95% CI 3.9-25.9), but not in subjects with lower intake of vitamin E. CONCLUSION:
      A significant positive correlation between NT levels and fasting glucose is
      evident only in the presence of a reduced intake of some antioxidant vitamins.
      These findings might explain, at least in part, the discrepant results of
      previous studies and, if confirmed by further studies, suggest a simple measure
      (a balanced diet) to alleviate the increased oxidative stress of diabetes.

PMID- 16108848
TI  - Low serum concentration of sulfatide and presence of sulfated lactosylceramid are
      associated with Type 2 diabetes. The Skaraborg Project.
AB  - AIMS: The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases
      exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is
      thereby able to influence insulin secretion through its presence in the islets. A
      closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in
      the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is
      secreted autonomically without the usual first phase response to glucose. The aim
      was to examine whether serum concentrations of these glycolipids are associated
      with Type 2 diabetes. METHODS: A case-control study, comprising 286 women and 283
      men, was designed using a population-based sample of patients with Type 2
      diabetes and a population survey. RESULTS: Low serum concentrations of sulfatide
      were associated with Type 2 diabetes, independent of traditional risk factors for
      diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval
      1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the
      highest tertiles. Type 2 diabetes was also associated with detectable amounts of
      sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women.
      After adjustment for confounding from other diabetes risk factors, these
      associations remained basically unchanged. The connections between sulfatide and
      Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each
      other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide
      concentration and positively correlated with sulf-lac-cer (both P < 0.0001,
      independently). CONCLUSIONS: We report a new, robust and highly significant
      independent association between Type 2 diabetes and serum concentrations of
      sulfatide in both sexes, and sulf-lac-cer in females. The associations were also
      independent of other known diabetes risk factors.

PMID- 16108849
TI  - Long-term influences of body-weight changes, independent of the attained weight,
      on risk of impaired glucose tolerance and Type 2 diabetes.
AB  - AIM: To investigate if weight gain during adulthood has effects on the risk of
      developing impaired glucose tolerance (IGT) or Type 2 diabetes beyond effect of
      attained weight. RESEARCH DESIGN AND METHODS: Data were obtained from a
      longitudinal study of two cohorts: one of juvenile-onset obese (n = 248) and one
      of randomly selected control (n = 320) men, weighed at average ages of 20, 33, 44
      and 51 years, respectively. RESULTS: For any given BMI, the risk of IGT was
      higher the greater the weight gain since age 20 (odds ratio of 1.10 per unit
      kg/m2 of BMI gain, confidence interval 1.03-1.17, P = 0.004), and weight gain
      during both the early and later ages contributed to the increased risk. Obese
      men, maintaining weight since age 20, had lower risk of IGT than non-obese men
      who became similarly obese by age 51. The risk of Type 2 diabetes increased by
      weight gain in early adult life, but not by more recent weight gain in the later
      periods, probably because of the development of Type 2 diabetes leading to weight
      loss. CONCLUSIONS: Independent of attained level of body weight in middle-aged
      men, weight gain is associated with increased risk of IGT, and is greater in
      those not overweight in childhood.

PMID- 16108850
TI  - Association of physical inactivity with components of metabolic syndrome and
      coronary artery disease--the Chennai Urban Population Study (CUPS no. 15).
AB  - AIM: The aim of the study was to assess the influence of physical activity on the
      components of metabolic syndrome (MS) in an urban south Indian population in
      Chennai. METHODS: The Chennai Urban Population Study (CUPS) is an epidemiological
      study involving two residential areas in Chennai in South India. Of the total of
      1399 eligible subjects (age > or = 20 years), 1262 individuals participated in
      the study. MS was diagnosed based on modified Adult Treatment Panel (ATP) III
      guidelines. Details about the physical activity were collected using
      questionnaire, which included job-related and leisure-time activities, and
      specific questions on exercise. Study individuals were then graded as light,
      moderate and heavy using a scoring system. We assessed the relationship between
      the grades of physical activity and the components of MS and coronary artery
      disease (CAD). Insulin resistance was calculated using the homeostasis assessment
      model (HOMA-IR). RESULTS: Prevalence of most of the components of MS (diabetes P
      < 0.001, obesity P = 0.003, abdominal obesity P < 0.001 and hypertension P <
      0.001) and MS per se (P < 0.001) increased significantly with decrease in
      physical activity. Among non-diabetic subjects, HOMA-IR was significantly higher
      in subjects who did light-grade activity compared with heavy-grade activity (P =
      0.041). Logistic regression analysis revealed physical activity to be
      significantly associated with MS [heavy activity: reference, moderate activity,
      odds ratio (OR) 1.639, (P = 0.017); light activity: OR 2.289, (P < 0.001)].
      Subjects in the light-grade activity group also had higher odds of CAD (OR 2.42,
      95% confidence interval 1.40, 4.24, P = 0.011), compared with the heavy-grade
      activity group. CONCLUSION: Physical inactivity is associated with the components
      of MS and CAD in this urban south-Indian population. Lifestyle changes focusing
      on increasing physical activity could help to prevent the exploding epidemic of
      MS and CAD in India.

PMID- 16108851
TI  - Glucose intolerance is associated with C-reactive protein and intima-media
      anatomy of the common carotid artery in patients with coronary heart disease.
AB  - AIMS: The purpose of this study was to examine the relationship between glucose
      intolerance and levels of hsCRP, calculated intima-media area (cIMa) of the
      carotid artery and flow-mediated dilation of the brachial artery in 122 patients
      with a myocardial infarction 1-12 months before inclusion and without known
      diabetes mellitus. METHODS: A standard oral glucose test (OGTT) was performed.
      Diabetes mellitus and impaired glucose tolerance (IGT) were defined according to
      the WHO criteria. Ultrasound measurement of cIMa of the carotid artery and flow
      mediated dilation of the brachial artery were analyzed. RESULTS: Patients with
      diabetes mellitus had higher hs-CRP compared with patients with IGT and those
      patients with normal glucose tolerance (P < 0.05). The greater cIMa of the
      carotid artery in those with diabetes mellitus compared with normal subjects
      failed to reach conventional levels of significance (P = 0.058). hs-CRP and cIMa
      were associated with plasma glucose 120 min after the glucose load (P < 0.05). A
      multiple stepwise regression analysis, including all variables significantly
      associated with plasma-glucose 120 min after glucose ingestion as independent
      variables, revealed an independent and significant association between plasma
      glucose 120 min after glucose ingestion in the OGTT and CRP (P < 0.05). No
      association was observed between glucose intolerance and endothelial function.
      CONCLUSION: Glucose intolerance was associated with hs-CRP and cIMa in patients
      with coronary heart disease without known diabetes mellitus. Thus, inflammation,
      atherosclerosis and impaired glucose tolerance are tightly interrelated disorders
      even in subjects without known diabetes mellitus.

PMID- 16108852
TI  - Left ventricular dysfunction in hypertensive patients with Type 2 diabetes
      mellitus.
AB  - AIMS: To characterize left ventricular function in hypertensive patients with
      Type 2 diabetes and normal ejection fraction, and to relate these findings to
      pathogenic factors and clinical risk markers. METHODS: We examined 70
      hypertensive patients with Type 2 diabetes mellitus with ejection fraction > 0.55
      and fractional shortening > 0.25, all without any cardiac symptoms. Thirty-five
      non-diabetic subjects served as control subjects. Left ventricular longitudinal
      function was examined by tissue Doppler derived myocardial strain rate and peak
      systolic velocities. RESULTS: Hypertensive patients with diabetes had a
      significantly higher systolic strain rate (-1.1 +/- 0.3 s(-1) vs. -1.6 +/- 0.3 s(
      1), P < 0.001) and lower systolic peak velocities (3.3 +/- 1.0 vs. 5.6 +/- 1.0
      cm/s, P < 0.001) compared with control subjects. Myocardial systolic strain rate
      correlated significantly to left ventricular mass (r = 0.40, P < 0.01) and to
      both HbA1c (r = 0.43, P < 0.01), and fructosamine (r = 0.40, P < 0.01), but was
      not related to serum levels of carboxymethyllysine, albuminuria, blood pressure
      (dipping/non-dipping), or oral hypoglycaemic therapy. Patients with diastolic
      dysfunction had significantly higher levels of urine albumin [21.0 (5-2500) mg/l,
      vs. 9.5 (1-360), P < 0.01], heart rate (78 +/- 13 vs. 67 +/- 10 b.p.m., P <
      0.005), and seated diastolic blood pressure (85 +/- 6 vs. 81 +/- 7 mmHg, P <
      0.05) and non-dipping diastolic blood pressure was more frequent. CONCLUSIONS:
      Long axis left ventricular systolic function was significantly decreased in
      hypertensive patients with Type 2 diabetes mellitus, and is associated with
      hyperglycaemia and left ventricular hypertrophy. Diastolic dysfunction was
      closely related to increased diastolic blood pressure, non-dipping and increased
      urinary albumin excretion.

PMID- 16108853
TI  - Comparison of processes and intermediate outcomes between South Asian and
      European patients with diabetes in Blackburn, north-west England.
AB  - BACKGROUND: Diabetes and its complications are more prevalent among South Asians
      than people of European origin and there is some evidence that patients of South
      Asian origin with diabetes receive poorer quality care. METHODS: Longitudinal
      study of patients with diabetes in Blackburn, UK. Processes of care indicators
      [measurement of blood pressure (BP), cholesterol and glycosolated haemoglobin
      (HbA1c)] and values of these intermediate outcomes were extracted for all
      patients registered on a diabetes information system for the period 1995-2001.
      Differences in processes of care indicators and intermediate outcomes between
      ethnic groups were estimated after adjusting for the potential confounding
      factors of sex, age and socioeconomic status (SES). Generalized estimating
      equations were used to model trends and to test for differences in trends over
      time. RESULTS: Process of care was similar in South Asian and European patients.
      Mean BP and cholesterol concentration fell during the study period. South Asians
      had a higher level of HbA1c throughout the study period. South Asians had lower
      levels of BP and cholesterol in 1995 but the differences diminished or were
      abolished over time. SES did not explain differences between ethnic groups.
      Analyses stratified by baseline levels of intermediate outcomes (above or within
      target) demonstrated improvements among above target patients were greater among
      European patients. CONCLUSIONS: Processes of care indicators are similar in
      diabetic patients of South Asian and European origin, irrespective of SES.
      However, there are worrying differences in improvements over time in the
      intermediate outcomes, and glycaemic control remained poorer among patients of
      South Asian origin patients throughout.

PMID- 16108854
TI  - Can a screening programme for diabetes be applied to another population?
AB  - AIMS: To compare the performance of a Danish diabetes screening protocol in
      populations from Denmark and Australia. METHODS: The populations used were the
      Inter99 population from Denmark and the AusDiab population from Australia. The
      Inter99 study included 6270 individuals aged 30-60 years, randomly selected from
      Copenhagen County. The AusDiab study included 7079 individuals also aged 30-60
      years, randomly selected from throughout Australia. In both studies, all
      individuals without known diabetes underwent an oral glucose tolerance test
      (OGTT). Screening using a Danish risk score as an initial step was followed by
      measurement of fasting plasma glucose (FPG). RESULTS: The characteristics of the
      study populations showed some differences in risk profile, with more individuals
      in the AusDiab study being obese, whilst in the Danish cohort, mean blood
      pressure was higher, less people took anti-hypertensive medication and there was
      a higher prevalence of screen-detected diabetes. Comparing the Australian and
      Danish populations, overall performance of the screening protocol was similar
      area under area receiver operator characteristic (ROC) curve 0.75 vs. 0.77,
      sensitivity 71 vs. 76% and positive predictive value (PPV) 6 vs. 9%. Small but
      statistically significant differences were observed in specificity (70 vs. 66%; P
      < 0.001) and percentage of the population requiring further testing (31 vs. 36%;
      P < 0.001). Combining the risk score with FPG > or = 6.1 mmol/l showed a similar
      pattern. Again, specificity was slightly but significantly higher in the
      Australian population (95 vs. 93%; P < 0.001) and percentage of the population
      requiring further testing was lower (5 vs. 8%; P < 0.001). CONCLUSIONS: The
      Danish risk score performed well when applied to a geographically different
      Caucasian population and is a suitable tool for detecting people at high risk of
      undiagnosed diabetes.

PMID- 16108855
TI  - Health-economic comparison of continuous subcutaneous insulin infusion with
      multiple daily injection for the treatment of Type 1 diabetes in the UK.
AB  - OBJECTIVES: The aim of this study was to project the long-term costs and outcomes
      of continuous subcutaneous insulin infusion (CSII) compared with multiple daily
      injections (MDI) in patients with Type 1 diabetes in the UK. METHODS: The CORE
      Diabetes Model is a peer-reviewed, validated model which employs standard
      Markov/Monte Carlo simulation techniques to describe the long-term incidence and
      progression of diabetes-related complications. It was used to simulate disease
      progression in a cohort of patients with baseline characteristics taken from
      published UK studies (mean age 26 years, duration of diabetes 12 years, mean
      HbA1c 8.68%). Direct costs for 2003 were calculated from a third-party payer
      perspective. Discount rates of 3.0% per annum were applied to costs and clinical
      outcomes. RESULTS: Treatment with CSII was associated with an improvement in mean
      quality adjusted life expectancy (QALE) of 0.76 +/- 0.19 years compared with MDI
      (12.03 +/- 0.15 vs. 11.27 +/- 0.14 years). Mean direct lifetime costs were pounds
      19,407 +/- 1727 higher with CSII treatment compared with MDI (pounds 80,511 +/-
      1257 vs. pounds 61,104 +/- 1249). This produced an incremental cost-effectiveness
      ratio (ICER) of pounds 25,648 per quality-adjusted life year (QALY) gained with
      CSII vs. MDI. The results were most sensitive to variation in hypoglycaemia rates
      and altering improvements in HbA1c associated with CSII therapy compared with
      MDI. CONCLUSIONS: Improvements in glycaemic control associated with CSII over MDI
      led to improved QALE owing to reduced incidence of diabetes-related
      complications. CSII was associated with an ICER of pounds 25,648 per QALY gained
      vs. MDI, representing good value for money by current standards in the UK.

PMID- 16108856
TI  - Diabetes service provision: a qualitative study of newly diagnosed Type 2
      diabetes patients' experiences and views.
AB  - AIMS: To explore newly diagnosed Type 2 diabetes patients' views about Scottish
      diabetes services at a time when these services are undergoing a major
      reorganization. To provide recommendations to maximize opportunities brought by
      the devolvement of services from secondary to primary healthcare settings.
      METHODS: Qualitative panel study with 40 patients newly diagnosed with Type 2
      diabetes, recruited from hospital clinics and general practices in Lothian,
      Scotland. Patients were interviewed three times over 1 year. The study was
      informed by grounded theory, which involves concurrent data collection and
      analysis. RESULTS: Patients were generally satisfied with diabetes services
      irrespective of the types of care received. Most wanted their future care/review
      to be based in general practice for reasons of convenience and accessibility,
      although they disliked it when appointments were scheduled for different days.
      Many said they lacked the knowledge/confidence to know how to manage their
      diabetes in particular situations, and needed access to healthcare professionals
      who could answer their questions promptly. Patients expressed a need for primary
      care professionals who had diabetes expertise, but who had more time and were
      more accessible than general practitioners. Patients who had encountered practice
      lead nurses for diabetes spoke particularly positively of these professionals.
      CONCLUSIONS: Nurses with diabetes training are particularly well placed to
      provide information and support to patients in primary care. Ideally, practices
      should run 'one-stop' diabetes clinics to provide structured care, with easily
      accessible dietetics, podiatry and retinopathy screening. Newly diagnosed
      patients may benefit from being made more aware of specific services provided by
      charitable organizations such as Diabetes UK.

PMID- 16108857
TI  - Hyperglycaemia and mortality of diabetic patients with candidaemia.
AB  - AIMS: To determine whether the degree of hyperglycaemia has an impact on in
      hospital mortality in diabetic patients with candidaemia. METHODS: A
      retrospective cohort study of 87 diabetic patients with candidaemia admitted
      between June 1995 and June 2003 was carried out at two medical centres. Patients
      were stratified into two groups: those with moderate hyperglycaemia (7 days post
      candidaemia mean blood glucose < 13.9 mmol/l) and those with severe
      hyperglycaemia (7 days post-candidaemia mean blood glucose > or = 13.9 mmol/l). A
      stepwise logistic regression analysis was performed to determine whether the
      degree of hyperglycaemia was a significant predictor of mortality. RESULTS:
      During the follow-up period from admission till discharge, 34 (39.1%) patients
      had died. Nine (69.2%) of 13 patients with severe hyperglycaemia have died while
      25 (33.8%) of 74 patients with moderate hyperglycaemia have died. Multivariate
      analysis identified three independent determinants of death; Apache II score > or
      = 23 [OR 8.1, 95% CI (2.6, 25.3), P = 0.0003], mean blood glucose levels 7 days
      post-candidaemia > or = 13.9 mmol/l [OR 6.8, 95% CI (1.2, 38.2), P = 0.03], and
      mechanical ventilation [OR 6.5, 95% CI (2.21), P = 0.03]. CONCLUSION: Severe
      hyperglycaemia is an important marker of increased mortality among hospitalized
      diabetic patients with candidaemia.

PMID- 16108858
TI  - Heel ulcers don't heal in diabetes. Or do they?
AB  - AIM: To obtain information on outcome of heel ulcers in diabetes. METHODS: Data
      were recorded prospectively on all patients with heel ulcers who were referred to
      a specialist multidisciplinary clinic between 1 January 2000 and 30 November
      2003. Outcomes were assessed on 31 March 2004. RESULTS: There were 157 heel
      ulcers in the patients referred in the period. Three ulcers were excluded from
      analysis because of associated osteomyelitis. Of 154 remaining ulcers (121 limbs;
      97 patients, 55 male; mean age 68.5 +/- 12.8 sd years), 101 (65.6%) healed after
      a median (range) 200 (24-1225) days. Of 53 non-healed ulcers, 11 (7.1% of 154)
      were resolved by major amputation, 30 (19.5% of 154) were unhealed at time of
      patient's death, and 12 (7.8% of 154) remained unhealed. Ulcers healed in 59 of
      97 affected patients (60.8%). Twenty-six patients (26.8% of 97) died during the
      period, of whom 20 died with ulcers unhealed. Worse outcomes were observed in
      larger ulcers (P = 0.001, Mann-Whitney U-test = 1883.5) and limbs with clinical
      evidence of peripheral arterial disease (P = 0.001, Mann-Whitney U-test =
      1163.00). Backward step-wise logistic regression analysis showed 70.1% of healing
      could be predicted from these two baseline characteristics. CONCLUSIONS: The
      common perception that 'heel ulcers don't heal' is not reflected in clinical
      practice. Outcome is generally favourable even in a population often affected by
      serious comorbidity and with limited life expectancy. These data can be used to
      help define management plans, as well as a basis for counselling of the
      individual patient.

PMID- 16108859
TI  - Relative role of major risk factors for Type 2 diabetes development in the
      historical cohort of the Brisighella Heart Study: an 8-year follow-up.
AB  - AIM: The aim of this study was to evaluate and quantify the role of different
      risk factors in the long-term development of Type 2 diabetes mellitus in a rural
      Italian population. METHODS: The Brisighella Heart Study (BHS; 1972-2003) is a
      prospective, population-based longitudinal epidemiological cohort involving 2939
      randomly selected subjects, aged 14-84 years, resident in the rural Italian town
      of Brisighella. For this study, we randomly selected 1441 adult subjects
      representative of the Brisighella population; consecutively visited during three
      BHS surveys. A step-wise Cox regression analysis determined the prognostic
      significance of each independent risk factor for the development of Type 2
      diabetes in the 8-year long follow-up. RESULTS: Blood pressure, high-density
      lipoprotein cholesterol, triglycerides, physical activity, total energy intake,
      and drug treatment had no effect on the incidence of diabetes. Age was a
      significant predictor of Type 2 diabetes when inserted alone in the model (P =
      0.007), but irrelevant when adjusted for baseline body mass index (BMI) and or
      fasting plasma glucose. Among these with impaired fasting glucose (IFG), the
      diabetes incidence/year was estimated to be 6.6% for men and 11.2% for women (P <
      0.001). Basal glycaemia under 6.1 mmol/l were not significant long-term
      predictors of diabetes development, while higher basal glycaemia and each level
      BMI were. CONCLUSION: Our findings confirm that IFG and BMI predict Type 2
      diabetes development in our population. This should help to identify effective
      approaches to prevention.

PMID- 16108860
TI  - Diabetes and hypertension in pregnancy in a rural community of Bangladesh: a
      population-based study.
AB  - AIMS: Gestational diabetes mellitus (GDM) is associated with increased infant
      mortality. Diabetes and infant mortality is higher in Bangladesh but the
      prevalence of diabetes and hypertension in pregnancy is not known. Thus, this
      study addressed the prevalence of diabetes and hypertension in pregnancy.
      METHODS: We selected 10 villages randomly in a union council of Nandail
      subdistrict. Following a population census (n = 14 382: male/female = 7476/6906)
      on demography and marital status, we interviewed 2205 married women (18-44 years)
      for detection of pregnancy. Of a total of 172 pregnancies, we investigated 147
      with a gestational age of 24-28 weeks for obstetrical history, clinical
      examination and blood pressure (BP). Fasting (FBG) and 2-h blood glucose (2hBG)
      were assessed by Hemocue cuvette. WHO diagnostic criteria were used. RESULTS: The
      overall prevalence (95% CI) of diabetes was 6.8% (1.88-9.32) and 8.2% (3.74
      12.64) according to FBG and 2hBG, respectively. The crude prevalence of systolic
      and diastolic hypertension was 6.8 and 5.4%, respectively. The median
      (interquartile range) values for age, BMI and FBG of the participants were 25.0
      (21.0-30.0) years, 19.5 (18.2-21.2) and 3.9 (3.6-4.3), respectively. The history
      of abortion, neonatal death and stillbirth was found in 19.9, 11.4 and 9.6%,
      respectively. The prevalence of GDM was higher among those with the history of
      stillbirth (15.4 vs. 6.0%) and neonatal death (11.8 vs. 6.2%) than those without.
      CONCLUSION: The prevalence of GDM in rural Bangladesh is comparable with any
      other population with higher prevalence of GDM. Increased morbidity and mortality
      among mothers and newborns in Bangladesh may, in part, be because of increased
      prevalence of GDM.

PMID- 16108861
TI  - Improved glycaemic control--an unintended benefit of a nurse-led cardiovascular
      risk reduction clinic.
AB  - AIMS: One hundred and ten patients with Type 2 diabetes were referred into a
      nurse-led cardiovascular risk reduction clinic. The primary aim of the clinic was
      to optimize blood pressure (BP) control and address cardiovascular risk factors.
      METHODS: Those attending outpatient clinics were referred into a nurse-led
      cardiovascular risk reduction clinic if BP was above 140/85 mmHg. There was no
      intervention strategy designed in the nurse clinic protocol to improve glycaemic
      control. RESULTS: Following attendance at the clinic, there was a significant
      improvement in HbA1c noted when patients were reviewed 9 months later. HbA1c
      improved from 8.7 +/- 1.6 to 8.1% +/- 1.6% (P < 0.001) in the whole cohort.
      Further analysis showed that, after excluding those who had received intervention
      to improve glycaemic control from another source, during the same period there
      remained a significant improvement in the non-intervention group of patients.
      CONCLUSION: Frequent regular contact and health education in a nurse-led clinic
      to reduce cardiovascular risk may improve HbA1c in the absence of any specific
      intervention to improve glycaemic control.

PMID- 16108862
TI  - British South Asians aged 13-16 years have higher fasting glucose and insulin
      levels than Europeans.
AB  - AIM: To examine whether plasma glucose, insulin resistance and markers of
      adiposity differed between British adolescents of South Asian and European
      origin. METHODS: School-based cross-sectional study (1998-2000), in which
      detailed measurements of adiposity, fasting plasma glucose and serum insulin were
      made in 90 South Asian and 1248 European pupils (overall 69% response rate).
      RESULTS: Compared with Europeans, South Asian subjects had higher mean fasting
      insulin levels (percentage mean difference 17.2%, 95% confidence interval 7.2
      26.1%, P = 0.001), a higher mean fasting glucose (mean difference 0.19 mmol/l,
      95% confidence interval 0.08-0.29 mmol/l, P = 0.0005) and a higher prevalence of
      impaired fasting glucose (> or = 6.1 mmol/l) (5.6% vs. 1.5%, odds ratio 3.9, 95%
      confidence interval 1.4-10.9, P = 0.004). Although South Asian children tended to
      have slightly higher indices of adiposity than Europeans (other than body mass
      index), the differences in glucose and insulin levels persisted after adjustment
      for adiposity and for pubertal status. CONCLUSIONS: The predisposition to Type 2
      diabetes observed in South Asian adults is apparent before adult life.
      Establishing the contributions of the childhood and fetal environments and of
      genetic factors to the development of these ethnic differences is an important
      priority. Prevention of Type 2 diabetes in British South Asians needs to begin
      before adult life.

PMID- 16108863
TI  - Antecedent hypoglycaemia attenuates vascular endothelial growth factor response
      to subsequent hypoglycaemia in healthy men.
AB  - AIM: The plasma concentration of vascular endothelial growth factor (VEGF) has
      recently been shown to increase sharply in response to hypoglycaemia and, thus,
      has been proposed as having a role in hypoglycaemia counter-regulation. Many
      counter-regulatory hormones show a reduced response after antecedent
      hypoglycaemia. We therefore investigated whether this decrease in responsiveness
      with repetitive hypoglycaemia also pertains to VEGF. METHODS: Three hypoglycaemic
      clamp experiments were performed on two consecutive days in 15 healthy men. VEGF
      response was assessed during the first and last hypoglycaemic period. RESULTS: As
      expected, plasma VEGF concentrations rose markedly during the clamps (P < 0.001).
      The increase was distinctly blunted during the third (+13 +/- 8 pg/ml) as
      compared with the first (+54 +/- 18 pg/ml) hypoglycaemic clamp (P = 0.046).
      CONCLUSION: This data confirms that circulating VEGF concentrations increase
      acutely during hypoglycaemia. Like the counter-regulatory hormones, the
      hypoglycaemia-induced rise in VEGF is attenuated after antecedent hypoglycaemia.
      The origin of increased systemic VEGF concentration during hypoglycaemia and its
      physiological role remains to be defined.

PMID- 16108864
TI  - Metformin reduces C-reactive protein but not complement factor C3 in overweight
      patients with Type 2 diabetes mellitus.
AB  - AIMS: To determine the influence of metformin treatment on plasma C-reactive
      protein (CRP) and complement factor C3. METHODS: A double-blind, placebo
      controlled trial of metformin in patients with poorly controlled Type 2 diabetes
      mellitus and body mass index > 25 kg/m2. CRP and C3 were analysed in stored
      plasma samples by in-house ELISAs. Patients attended two baseline visits before
      randomization and subsequently attended at 3, 6, 12 and 24 weeks post
      randomization. All patients gave informed consent according to a protocol
      approved by the Leeds Teaching Hospitals Research Ethics Committee. RESULTS:
      Baseline CRP in the patients randomized to placebo [1.33 (0.79, 2.25) mg/l] and
      metformin [1.24 (0.89, 1.71) mg/l] were similar (P = 0.8). Baseline CRP
      correlated with baseline C3 (r = 0.366) and HbA1c (r = 0.327). The difference in
      ratios of CRP levels at each visit to baseline between placebo- (n = 16) and
      metformin-treated (n = 26) subjects was significantly different at the 12-week (P
      = 0.002) and 24-week (P = 0.03) visits. The difference in CRP ratios between the
      two treatment groups remained significant after accounting for glycaemic control
      at both visits (P = 0.001 and P = 0.003, respectively). Baseline C3 was
      correlated with CRP. Baseline C3 was lower in the placebo-treated group [0.97
      (0.88, 1.05) mg/ml] compared with the metformin-treated group [1.09 (1.02, 1.17)
      mg/ml, P = 0.03]. There was no difference in the mean change in C3 at any visit
      from baseline between placebo- and metformin-treated groups. CONCLUSION:
      Metformin may have a specific interaction with mechanisms involved in CRP
      synthesis or secretion, not directly related to improved insulin sensitivity and
      dampening of chronic inflammation.

PMID- 16108865
TI  - Cigarette smoking and prevention of Type 2 diabetes mellitus.

PMID- 16108867
TI  - Acute brain injury with hemiparesis due to hypoglycaemia.

PMID- 16108868
TI  - Acute brain injury in hypoglycaemia-induced hemiplegia.

PMID- 16108870
TI  - Mortality and diabetic neuropathy.

PMID- 16108871
TI  - Hypoglycaemia and driving.

PMID- 16108872
TI  - Diabetic patients with a HbA1c of 6.7% feel better than patients with a HbA1c of
      9.1%.

PMID- 16108877
TI  - Long-term outcome of per anum intersphincteric rectal dissection with direct
      coloanal anastomosis for lower rectal cancer.
AB  - OBJECTIVE: The authors have performed per anum intersphincteric rectal
      dissection. With direct coloanal anastomosis for cases of lower rectal cancer in
      which the distal surgical margin is difficult to secure by the double stapling
      technique. The aim of this study was to evaluate the long-term outcome and to
      clarify the surgical indications for this operation. PATIENTS AND METHODS:
      Between 1993 and 2002, 31 patients underwent per anum intersphincteric rectal
      dissection with direct coloanal anastomosis. Of these, two patients (one stage 0
      and one stage IV) were excluded from the analysis of oncological outcome. The
      remaining 29 patients formed the basis of this study. The median follow-up was 57
      months (range 6-106 months). RESULTS: Local recurrence and distant metastasis
      developed in 9 and 3 patients, respectively. Local recurrence rate for pT1 was
      significantly lower than that for pT2/T3 disease. The local recurrence rate cases
      with tumours less than 3 cm was significantly lower than that for tumours sized 3
      cm or more. The distant metastasis rate for cases with lymph node metastasis was
      significantly higher than that for cases without lymph node metastasis. There was
      an association between distant metastasis and TNM or pT stage. The overall
      survival rates for stage I, II and III were 85%, 80% and 89%, respectively. No
      significant difference was seen in total Cleveland Clinic incontinence score
      between per anum intersphincteric rectal dissection with direct coloanal
      anastomosis and the double stapling technique. CONCLUSION: The surgical
      indications of this operation should be limited to patients with T1 rectal cancer
      or tumours less than 3 cm.

PMID- 16108878
TI  - Pedicled flaps in the treatment of nonhealing perineal wounds.
AB  - INTRODUCTION: A persistent sinus is an annoying complication following
      proctectomy. We examined the experience of a single colorectal surgeon in
      treating this condition using pedicled flaps. METHODS: Case note review of all
      patients undergoing gracilis muscle transposition, Rectus abdominis muscle flap
      or omental flap for persistent perineal sinus. RESULTS: Seventeen patients were
      identified: seven had gracilis muscle transposition, eight had omental
      transposition and two had a rectus abdominis flap. 13/17 patients who underwent a
      flap had a persistent sinus following proctectomy for Inflammatory bowel disease.
      Four patients who had a gracilis muscle transposition achieved healing. Seven out
      of eight patients had good results with omental transposition. One patient did
      well after a rectus abdominis flap. CONCLUSIONS: A gracilis transposition is a
      relatively simple operation with minimal morbidity useful for superficial sinuses
      not requiring a muscle bulk. A rectus abdominis flap is a more complex
      specialized procedure with better results especially in dealing with larger
      cavities but it may compromise future stoma sites. Omentoplasty has excellent
      results, but is only available in some patients.

PMID- 16108879
TI  - Modified technique for parastomal hernia repair in patients with intractable
      stoma-care problems.
AB  - OBJECTIVE: Although stoma relocation is generally the first choice of treatment
      for parastomal hernia, a repair using polypropylene prosthetic mesh is sometimes
      employed in cases of parastomal hernia recurrence. Use of this mesh, however, has
      been associated with a high risk of bowel erosion, adhesions formation, and
      fistulization. We therefore began to use expanded polytetrafluoroethylene (ePTFE)
      mesh to perform an onlay parastomal hernia repair. Our initial clinical
      experience with this procedure is described. PATIENTS AND METHODS: Sixteen
      patients aged 39-70 years with intractable stoma problems underwent a modified
      intra-abdominal onlay technique with implantation of a large (26 x 36 cm) sheet
      of ePTFE mesh. RESULTS: During a median follow-up of 29 months (range, 5-52
      months), no mesh-related bowel erosion, fistulization, or adhesion formation were
      observed. Two patients had a recurrence of the hernia due to technical failure.
      Re-operation in one of these resulted in wound dehiscence and removal of the
      contaminated mesh. Another patient developed intestinal obstruction
      postoperatively. The mesh was removed, and a gastrointestinal stromal tumour was
      found. Finally, a nonmesh related small bowel erosion required removal of the
      mesh in one patient. All other patients had full relief of symptoms. CONCLUSION:
      The modified onlay technique using a large sheet of ePTFE prosthetic mesh is a
      feasible option for treatment of parastomal hernia recurrence. Possible
      advantages of the procedure include stoma preservation, strengthening of the
      abdominal wall, and a reduced risk of recurrence, contamination, fistulization,
      and bowel adhesions and erosion.

PMID- 16108880
TI  - How has the 'two-week wait' rule affected the presentation of colorectal cancer?
AB  - OBJECTIVE: To assess the impact of the 'two-week wait' rule on the presentation
      of colorectal cancer. METHODS: A retrospective study of all patients referred to
      a fast-track clinic in a colorectal cancer centre over an 18-month period,
      documenting outcome, especially colorectal cancer diagnosis. Comparison was made
      with patients diagnosed with colorectal cancer presenting via other routes in the
      same time period. RESULTS: Over an 18-month period, 462 patients were seen in the
      fast-track clinic and 64 (13.8%) were diagnosed with colorectal cancer. A further
      131 patients with colorectal cancer presented to the department in the same time
      period through other means; 66 via standard out-patient letters, 26 from other
      departments and 39 (20%) as emergency admissions. Median (range) time to first
      clinic was 12 (2-28) days for fast-track and 24 (1-118) days for standard
      referrals (P < 0.0001); median time to first treatment was a further 36 (9-134)
      and 36.5 (1-226) days, respectively. The fast-track cohort had more advanced
      staging than those referred by standard letter. There were 19 Dukes' B, 22 Dukes'
      C and 14 Dukes' D cancers in the fast-track group compared with 28 Dukes' B, 25
      Dukes' C and 6 Dukes' D in the standard referral group. After patient interview,
      only 337 (73%) of 462 fast-track patients appeared to fulfil the referral
      criteria but of the 64 diagnosed with cancer, 59 (92%) satisfied the criteria. Of
      the 66 patients with cancer referred by standard letter, 61 (92%) fulfilled the
      criteria. CONCLUSION: Patients referred to the fast-track clinic were seen
      quicker than those referred by standard letter, but they tended to have more
      advanced disease. The fast-track referral criteria were fulfilled by most
      patients with cancer (whether or not they were referred to the fast track
      clinic), confirming their validity. After detailed interview in the clinic, a
      quarter of fast-track referrals were found not to satisfy referral criteria,
      suggesting that prioritization in primary care could be improved.

PMID- 16108881
TI  - Feasibility and morbidity of reversal of Hartmann's.
AB  - OBJECTIVE: Reversal of Hartmann's is a major surgical procedure and associated
      with substantial morbidity and mortality. METHOD: This study retrospectively
      analysed the data at a single centre over an eight-year period to assess the
      clinical results and morbidity of reversal of Hartmann's. RESULTS: One hundred
      and ten Hartmann's procedures were performed during the period. Only 66 (61%) of
      patients had a reversal. Advanced age and comorbidity were the primary reasons
      for not reversing. Complications among the 66 patients (36 males and 30 females)
      who underwent reversal occurred in 26 (41%). There were no deaths. Patients who
      underwent reversal were ASA 2 (60%), ASA 3 (25%) and ASA 4 (4.6%). Univariate
      analysis demonstrated a significant association between complications following
      reversal and ASA grade (P =0.01), and hypertension (P = 0.03) There was no
      correlation between the patient variables and anastomotic leakage. Multiple
      logistic regression analysis showed a significant influence of hypertension,
      smoking and ASA grade on complications. CONCLUSIONS: About 40% of patients who
      undergo Hartmann's procedure will not have a reversal. Reversal is a feasible
      operation for selected patients, but there is a high complication rate.

PMID- 16108882
TI  - Prospective study on the role of the CT scan in patients with an acute abdomen.
AB  - OBJECTIVES: Recent reports indicate that early CT scan (within 24 h) increases
      diagnostic accuracy, reduces hospital stay and mortality in patients with an
      acute abdomen. The aim of this study was to assess the surgeons' use of CT in
      patients with an acute abdomen and the impact of this on diagnostic accuracy and
      mortality. PATIENTS AND METHODS: Patients older than 25 years admitted as an
      emergency with acute abdominal pain were prospectively evaluated. RESULTS: Two
      hundred and eleven patients fulfilled the inclusion criteria including 129 women
      and 82 men with a mean age of 62.4 years (range 27-92 years). The correct
      diagnosis on admission was made in 99 (47%) patients. CT was performed in 81
      (38%), including 24 who had the scan performed within 24 h of admission. The
      sensitivity, specificity and accuracy of CT were 86%, 79% and 84%. CT was
      considered to have changed clinical management in 40 patients. Fifteen patients
      died, and one death may have been prevented by an early CT. Five had a delay in
      diagnosis of a serious condition; all could have been prevented by early CT.
      CONCLUSION: Selective use of CT increases diagnostic accuracy and improves the
      management of patients with an acute abdomen. Clinical trials are necessary to
      assess outcome following selective vs routine use of CT in this group of
      patients.

PMID- 16108883
TI  - Colovesical fistula--is a surgical approach always justified?
AB  - OBJECTIVE: There is a tendency to over investigate patients with colovesical
      fistula and to advise surgical intervention as the sole course of action. Most
      patients are elderly and operative intervention often carries a high morbidity
      and mortality. PATIENTS AND METHODS: A retrospective study of 50 patients
      diagnosed with a colovesical fistula over a 12-year period was undertaken at our
      institution. The notes of all these patients were reviewed using a standardized
      proforma to look at the referral pattern, symtomatology, investigation, treatment
      and outcomes. RESULTS: Data analysis showed the median age of these patients to
      be 70 years with 92% having either pneumaturia or faecaluria or both as a
      symptom. There was no significant difference in disease-specific mortality in
      patients with benign colovesical fistula undergoing surgical intervention and
      patients treated conservatively. There was not a single documented case of
      septicaemia despite untreated colovesical fistula being present for a cumulative
      total of 3254 weeks. There was no statistically significant decline in the renal
      function due to the disease. CONCLUSION: We suggest that fewer investigations be
      performed for the diagnosis of colovesical fistula and conservative management
      offered to patients with benign pathology.

PMID- 16108884
TI  - Response to neoadjuvant therapy for rectal cancer: influence on long-term
      results.
AB  - OBJECTIVE: Pre-operative treatment with chemoradiotherapy (CRT) seems to improve
      local control and overall survival in patients with rectal cancer. The aims of
      the study were to analyse the impact on overall, disease free and cancer related
      survival of tumour response to pre-operative CRT and to analyse the influence of
      the degree of response on long-terms results. PATIENTS AND METHODS: Patients with
      a locally advanced rectal cancer, treated by pre-operative CRT were studied. A
      radical resection of the rectal tumour with mesorectal excision was performed
      within 6-8 weeks. Judged on the final TNM classification patients were considered
      responders when the tumour showed histologically a complete response, microscopic
      residual disease or a partial response. Non-responders were those in whom the
      extent of disease remained stable or progressed. Results Radical excision was
      performed in 103 patients, and a palliative resection in five. Forty-three
      patients underwent abdominoperineal resection and 65 anterior resection of the
      rectum. Seventy-one (65.7%) patients showed a response to CRT, while 37 (34.3%)
      did not. The overall local and distant recurrence rates were 6.8% and 21.3%.
      Tumour recurrence (P < 0.008) and disease free survival (P < 0.007) were
      significantly different in responders and nonresponders. Of the 71 responders, 16
      had a pathological complete response, 27 had persisting microscopic disease and
      28 had macroscopic residual disease. No differences in cancer specific outcome
      were observed in these groups. CONCLUSION: Pathological response to pre-operative
      CRT is associated with improved tumour recurrence and disease-free survival
      rates. Any response to pre-operative CRT appears to improve outcomes as much as a
      complete response.

PMID- 16108885
TI  - Evolution of the two-week rule pathway--direct access colonoscopy vs outpatient
      appointments: one year's experience and patient satisfaction survey.
AB  - Abstract Objectives The aim of this study was to compare the effectiveness of
      Direct access colonoscopy (DAC) vs outpatient appointments for two-week rule
      colorectal cancer referrals and to evaluate the satisfaction of patients referred
      through these routes. Patients and methods Data were collected prospectively from
      January 2003 to December 2003 on patients who were referred for DAC or outpatient
      appointments at the discretion of the referring General practitioner via the
      Lower GI two-week rule pathway. A postal questionnaire was used to survey patient
      satisfaction. Results Six hundred and thirty-nine patients were referred via the
      two-week rule pathway; 188 patients underwent colonoscopy at their initial
      hospital visit and 19 (10.1%) colorectal cancers were diagnosed; 442 patients had
      an outpatient appointment and 32 (7.2%) colorectal cancers were identified. There
      were 7 (1%) inappropriate referrals and 2 patients refused investigations. All
      outcome parameters measured were reduced for patients referred directly for
      colonoscopy including time to definitive investigations (Median 9 vs 52 days P <
      0.0001), time to histological diagnosis (Median 14 vs 42 days P < 0.0001) and
      time to treatment (Median 55 vs 75 days P < 0.0483). One hundred and seventy
      patients were surveyed by the postal questionnaire of whom 127 (75%) responded.
      Ninety-eight percent of patients were satisfied with the service provided. Four
      (6.6%) of 60 patients who had undergone direct access colonoscopy expressed a
      desire to be seen at the outpatient department initially. Conclusions Direct
      access colonoscopy results in significantly reduced times to histological
      diagnosis and definitive treatment in patients with colorectal cancer. Patients
      can be directly admitted for investigations bypassing the outpatient clinic
      without affecting patient satisfaction.

PMID- 16108886
TI  - A technically difficult endorectal ultrasound is more likely to be inaccurate.
AB  - OBJECTIVE: Endorectal ultrasound (ERUS) is well established as an accurate
      modality for local staging of rectal tumours. The aim of this study was to
      identify reasons for inaccurate staging of tumours, and to assess whether
      difficulties encountered during scanning are likely to influence accuracy.
      PATIENTS AND METHODS: ERUS was performed by a single operator using a 10 MHz
      rigid instrument. One hundred and seventeen patients that had both ERUS and
      surgery are included in this study (patients that had pre-operative radiotherapy
      were excluded). During ERUS, procedural conditions and limiting factors were
      recorded. Data was collected prospectively. RESULTS: In 78 (66.7%) patients no
      technical difficulty was encountered during ERUS. In this group accuracy was 80%
      for T-stage and 77% for N-stage. Specific reasons for inaccuracy identified in
      this group were: inflammatory lymph nodes (from a tumour associated abscess and a
      colovesical fistula) and deep biopsy causing a submucosal defect with intramural
      haemorrhage in benign lesions (2 cases). In the remaining 39 (33.3%), the
      following problems were encountered: stenotic lesions (23), patient discomfort
      (8), poor bowel preparation (6), and scarring from previous surgery (2). In 11
      patients from this group, the scan was considered inconclusive and no stage could
      be determined. For the other 28, the accuracy for T-stage was 68% and for N-stage
      67%. CONCLUSION: A technically difficult ERUS is likely to give an inconclusive
      or inaccurate result for both T-stage (P = 0.001) and N-stage (P = 0.003). In
      this situation a repeat scan may be considered (where appropriate).
      Alternatively, further assessment by MRI or flexible endoscopic ultrasound may be
      considered.

PMID- 16108887
TI  - Analysis of adenocarcinoma of the colon and rectum: detection of human
      papillomavirus (HPV) DNA by polymerase chain reaction.
AB  - OBJECTIVE: The aim of the present work was to evaluate the presence of human
      papillomavirus genotypes in malignant and normal mucosa of the colon and rectum
      in order to determine if a relationship exists between HPV infection and colon
      neoplasms. MATERIALS AND METHODS: Thirty normal colon tissues and 54 sporadic
      adenocarcinomas were screened for HPV positivity using nested-PCR. Detection of
      viral types 6, 11, 16, 18, 33, 34 and 51 was performed by the LIS-SSCP (Low Ionic
      Strength-Single Strand Conformational Polymorphism) procedure. RESULTS:
      Significant differences in high risk HPV infection were found between normal
      samples and adenocarcinomas (P < 0.001). Among the cases, an inverse association
      between HPV infection and Dukes staging was also found (P = 0.020). Finally,
      there was no significant association between HPV and some classical
      clinicopathological features, although a gradient of infection form rectum to
      cecum was evident. CONCLUSION: The present study demonstrates that HPV may infect
      the glandular mucosa of the colon and suggests a possible association between HPV
      and colorectal cancer.

PMID- 16108888
TI  - Acute colonic pseudo-obstruction following major orthopaedic surgery.
AB  - OBJECTIVE: Acute colonic pseudo-obstruction (ACPO) has been linked with multiple
      aetiologies including orthopaedic surgery. However, the actual incidence and
      natural progression are not well described in these patients. We aim to assess
      the incidence of ACPO in patients undergoing elective orthopaedic procedures, and
      to examine for potential exacerbating factors. PATIENTS AND METHODS: All patients
      from the orthopaedic directorate that had abdominal imaging in the five years
      from August 1998 to August 2003 were identified from radiology archives. A manual
      search of the patients' notes was conducted with data recorded on the patients'
      history, operative details and their postoperative course including their
      haematological and biochemical results. Details regarding their ACPO were
      documented with respect to the onset of symptoms, how the diagnosis was achieved,
      what treatment was instigated and how the condition progressed. A control group
      of age and sex matched patients was included for comparison. RESULTS: Thirty-five
      patients with ACPO were identified. The operations included 21 hip replacements,
      10 knee replacements and 4 spinal operations. The incidence of ACPO was 1.3%,
      0.65% and 1.19%, respectively. In comparison to control patients, patients with
      ACPO had a lower postoperative serum sodium (P = 0.001), a higher serum urea (P =
      0.021) and remained in hospital longer (P < 0.001). CONCLUSION: ACPO is uncommon
      in orthopaedic patients, however, its occurrence results in prolonged hospital
      stay. Attention to patients' postoperative fluid balance and biochemical status
      may reduce the incidence.

PMID- 16108889
TI  - Thirty-day mortality after surgery for colorectal cancer in Denmark.
AB  - OBJECTIVE: This study aimed to estimate the 30-day mortality after colorectal
      cancer (CRC) surgery in Denmark. Mortality was compared to other studies, and
      between departments, unadjusted and adjusted for case-mix. MATERIALS AND METHODS:
      All patients in Denmark with a first-time colorectal adenocarcinoma operated
      between 1 May 2001 and 31 December 2002 were eligible, 5187 patients were
      included. Mortality was adjusted for age, sex, urgency, tumour location, Dukes'
      stage and ASA-score. RESULTS: The 30-day mortality in Denmark after CRC-surgery
      was 9.9%. Adjusted for case-mix, four departments had significantly higher
      mortality than average. The variation between the 44 departments was significant
      both for radically operated (P = 0.02) patients and for all operated patients (P
      = 0.01). CONCLUSION: The 30-day mortality in Denmark seems to be higher than in
      studies from other countries, but the lack of comparable nationwide studies makes
      it difficult to evaluate. To uncover the reasons for the departments to diverge
      significantly from average, further studies are needed.

PMID- 16108890
TI  - Double-blind randomised trial comparing 5-fluorouracil plus leucovorin to placebo
      for metastatic colorectal carcinoma.
AB  - OBJECTIVE: Previous randomised trials of chemotherapy for metastatic colorectal
      cancer have not concealed the allocation of treatment from participants. Most of
      these unblinded trials showed improved survival with chemotherapy. This trial
      used a double-blind design to test the hypothesis that there is no difference
      between the effect of 5-fluorouracil plus leucovorin and the effect of placebo on
      the survival of subjects with metastatic colorectal cancer. PATIENTS AND METHODS:
      In one hospital, 147 subjects with metastatic colorectal cancer were studied from
      1989 to 2001. 73 were allocated chemotherapy with 5-fluorouracil plus leucovorin.
      74 were allocated placebo. The primary end point was survival after
      randomization. Secondary end points were performance score, quality of life,
      serum level of carcinoembryonic antigen (CEA) and toxicity of treatment. RESULTS:
      One hundred and forty-two patients were followed up until death. The median
      survival time in the chemotherapy group was 8.7 months (95% confidence interval
      (CI) 6.9-11.0 months) compared to 6.7 months in the placebo group (95% CI 5.3-7.9
      months). Chemotherapy did not affect performance status but slowed the rise of
      CEA and caused appreciable toxicity. CONCLUSIONS: In this double-blind trial,
      chemotherapy with 5-fluorouracil plus leucovorin did not improve survival, did
      not impair performance, but caused appreciable toxicity.

PMID- 16108891
TI  - Staged mucosal advancement flap for the treatment of complex anal fistulas:
      pretreatment with noncutting Setons and in case of recurrent multiple abscesses a
      diverting stoma.
AB  - OBJECTIVE: To assess the efficacy of a staged strategy for the treatment of
      complex perianal fistula. METHODS: Between January 1999 and April 2003 all
      consecutive patients with complex perianal fistulas were treated according to a
      staged strategy. Fistula tracks originating from the middle third or upper part
      of the anal sphincter were included. Patients were examined for recurrent
      fistulas and complaints of incontinence and soiling. Initial treatment consisted
      of a noncutting seton with or without a diverting stoma. Definitive surgical
      treatment consisted of an advancement flap or fistulotomy. RESULTS: Thirty
      patients were included (median age; 42 years, range 22-68 years). Seven had
      Crohn's disease without signs of rectal and anal involvement other than the
      fistula. At a median follow up of 22 months (range 8-52 months) in 29 (97%)
      patients, the wounds had healed completely; 7 (22%) patients subsequently
      developed a recurrent fistula and minor soiling occurred in 7 (23%) patients.
      CONCLUSION: Initial treatment with a seton with and without a diverting stoma
      minimizing inflammatory activity at the fistula site before definitive surgical
      treatment gave good results in this difficult group of patients.

PMID- 16108892
TI  - Management of the rectal stump after emergency sub-total colectomy: which
      surgical option is associated with the lowest morbidity?
AB  - OBJECTIVE: To identify the preferred surgical management of the rectal stump
      after emergency subtotal colectomy (ESC) for acute severe colitis by assessing
      the morbidity associated with each option. PATIENTS AND METHODS: Consecutive
      patients undergoing ESC at a district general hospital between 1999 and 2004 were
      retrospectively audited for pathology, rectal stump complications and length of
      postoperative hospital stay (POS). RESULTS: Thirty-seven ESCs were performed, 34
      were undertaken for disease refractory to medical treatment, 2 for toxic mega
      colon and 1 for perforation. Thirty-four cases were for ulcerative colitis, 2
      Crohn's colitis and 1 infective colitis. Twenty-seven had an intraperitoneal and
      10 a subcutaneously placed closed rectal stump. The median POS for patients with
      a subcutaneously placed stump was shorter than for those with an intraperitoneal
      stump, 8 and 15 days, respectively (P = 0.04). Two patients had leakage from an
      intraperitoneal stump, prolonging POS (33 and 193 days). Three of the
      subcutaneous stumps leaked causing wound infection but not prolonging the POS (6,
      7 and 16 days). CONCLUSION: Avoiding a second stoma by closing the rectal stump
      after ESC has been confirmed as acceptable practice by studies over the last 15
      years, reporting no overall increase in complications. The location of a closed
      rectal stump appears to influence the incidence of pelvic sepsis. The lowest
      pelvic sepsis rate is associated with subcutaneous placement; despite a higher
      wound infection rate this option appears to be associated with a lower total
      morbidity reflected in a shorter POS.

PMID- 16108893
TI  - Effect of sacral neuromodulation for faecal incontinence on sexual activity.
AB  - INTRODUCTION: Faecal incontinence affects a percentage of the population and can
      have a significant effect on their ability to establish and maintain sexual
      relations. PATIENTS AND METHODS: Sixteen consecutive patients with permanent
      sacral neuromodulation (SNM) for faecal incontinence completed a 'Sex Life
      Questionnaire' at their follow up visit to ascertain whether there was any
      improvement in this aspect of their life. RESULTS: Nine of the sixteen patients
      was sexually active. These nine patients (median age 56 (35-61) years) had a
      significant reduction in faecal incontinence episodes per week from a median of
      12 (1-55) to 1.5 (0-8.5) (P = 0.008). All nine patients reported that their sex
      life had been affected by feacal incontinence prior to SNM and seven had felt
      benefit from implantation. The median improvement in their sex life was 40% (1
      100) and the percentage improvement was inversely correlated to age (r = -0.834,
      P = 0.005). CONCLUSION: SNM improves the quality of sexual activity in 78% of
      patients. More improvement seems to be gained the younger the patients.

PMID- 16108896
TI  - Restoration of anal continence after ileal pouch anal procedure with partial
      excision of anal sphincter by means of an artificial bowel sphincter.

PMID- 16108897
TI  - Finding the source of a fistula.

PMID- 16108898
TI  - Islamic practices: informed consent for stoma.

PMID- 16108899
TI  - Is there evidence to support delaying stoma formation in Fournier's gangrene.

PMID- 16108900
TI  - Co-existence of true colonic diverticula with angiodysplasia.

PMID- 16108902
TI  - Biomarkers of exposure to passive smoking of school children: frequency and
      determinants.
AB  - This study aims to assess the extent of children' exposure to ETS and quantify
      potential determinants. A total of 2767 children aged 5-14 years participated in
      an environmental survey in East Germany in 1998-1999 (participation rate 75.9%).
      A subgroup of 979 children between the ages of 11 and 14 years with complete data
      on nicotine and cotinine in urine were selected for this analysis. This study
      population consisted of 73 self-reported smokers (7.5%), 793 non-smokers (81%)
      and 113 children with missing data on smoking status (11.5%). Nicotine and
      cotinine concentrations in spontaneous urine sample were determined by high
      performance liquid chromatography methods with ultraviolet-detection and
      corrected for creatinine. Approximately 40% of self-reported non-smokers were
      exposed to environmental tobacco smoke (ETS) at home. Non-smoking children
      exposed to parental tobacco smoke at home compared with not exposed showed in
      average higher nicotine and cotinine concentration (geometric mean 4.7 microg/l
      vs. 1.4 microg/l and 8.1 microg/l vs. 2.7 microg/l) and the adjusted odds ratio
      (OR) for detectable biomarkers ranged between 17 and 22. There were increased
      rates of detectable biomarkers in urine with increasing numbers of smoked
      cigarettes in the household (adjusted OR increased from 8 to 54). Maternal
      smoking showed a stronger effect than paternal smoking. Furthermore, low parental
      education, cold season, height of dwelling (<or=2.40), urine collected on Monday
      were statistically significant associated with high nicotine and cotinine
      excretion levels. Children exposed to parental smoke showed much higher biomarker
      levels than the non-smoking spouse of an adult smoker. Therefore, children need
      specifically protection from ETS at home. PRACTICAL IMPLICATIONS: As children
      showed a higher internal exposure compared with adults the health hazards
      association with passive smoking might have a more serious effect in children.
      Children are unable to complain and unable to remove themselves from tobacco
      smoke exposure. Thus, parents should make sure that their children live in a
      smoke free environment. Each country should take all necessary legislative and
      regulatory measures which forbids smoking in public places and the home
      environment even if it requires sacrifices by the parents.

PMID- 16108903
TI  - Health and social impacts of improved stoves on rural women: a pilot intervention
      in Sindh, Pakistan.
AB  - To assess the acceptability, social and health impacts of improved stoves among
      women. A cross-sectional study was conducted from April to May 2002 among
      households using improved stoves in the two villages of District Thatta and
      Hyderabad, Sindh, Pakistan. A questionnaire was administered to 45 women using
      improved stoves named Smoke Free Stoves (SFS). The same questionnaire was
      administered to a sample of 114 women, using Traditional Stoves (TS). Carbon
      monoxide (CO) levels were measured in a sample of both groups. Multivariate
      analysis was carried out to adjust for confounders. In addition, focus group
      discussions (FGDs) were conducted to evaluate the perception of women regarding
      acceptability and impact of SFS on women. A majority of women reported that SFS
      produce less smoke and have a beneficial impact on their health. In the
      multivariate analysis, symptoms of dry cough (AOR=0.61; 95% CI 0.26-1.41),
      sneezing (AOR=0.54; 95% CI 0.22-1.30) and tears while cooking (TWC) (AOR=0.51;
      95% CI 0.21-1.21) are less likely to occur in women using SFS compared to TS.
      However, the results were not statistically significant possibly due to the small
      sample. The mean (+/-s.e.) CO levels were 15.4+/-3.4 ppm in SFS and 28.5+/-5.7
      ppm in TS kitchens with a mean difference of -13.1 (95% CI -29.5 and 3.2). The
      results indicate a trend favorable for SFS and suggest that a larger scale
      project should be undertaken to reach to a definitive conclusion, ideally using a
      longitudinal design. PRACTICAL IMPLICATIONS: In order to enhance IAQ in kitchens
      in developing regions of the world stoves for burning of biomass should be
      constructed in a way that the emission of fuel gases are low. In this way the
      risk of negative health effects will be reduced.

PMID- 16108904
TI  - Comparison of formaldehyde emission from building finishing materials at various
      temperatures in under heating system; ONDOL.
AB  - The objective of this research was to investigate the effect of various
      temperatures, room, 37 and 50 degrees C, on formaldehyde emission from floor
      materials, such as laminate and plywood floorings, and furniture materials, such
      as MDF and particleboard veneered with decorative paper foil, by desiccator's
      method. The temperature conditions were set up by, measuring the temperature in a
      Korean under heating system. To maintain an indoor air temperature of 20 degrees
      C, the temperature of the flooring surface was about 37 degrees C and the
      temperature of the cement mortar was 50 degrees C. The initial formaldehyde
      emission of the laminate flooring and plywood flooring was 1.44 and 0.63 mg/l,
      and for MDF and particleboard it was 4.73 and 4.95 mg/l, respectively. Floor
      materials were under E1 grade while furniture materials were under E2 grade in
      terms of formaldehyde emission. Because of the under heating system, the flooring
      materials were exposed to 37 and 50 degrees C, while the furniture materials
      mostly existed at room temperature. At 37 and 50 degrees C, the formaldehyde
      emission level of the flooring materials was already under 0.3 ppm (F level by
      JIS A 1460, application possibility without area limit) after 10 days and the
      emission had decreased further (0.03-0.10 mg/l) after 28 days. These levels are
      not injurious to the human body and will not cause sick house syndrome (SHS). The
      problem, however, is the furniture materials such as MDF and particleboard. As
      these materials are not exposed to high temperature (50 degrees C in this
      experiment) in living condition, it was still E2 grade of formaldehyde emission
      level at room temperature remained even after 28 days. Although there will be
      variations with the volume of furniture materials and the indoor conditions,
      furniture materials are the principal cause of indoor air quality pollution in
      Korean with the under heating system. PRACTICAL IMPLICATIONS: Koreans spend most
      of their time sitting on ONDOL (heated) floors, with their buttocks always in
      contact with the floor surface. The flooring materials are exposed to high
      temperatures (37-50 degrees C) why the effect of bake-out is rapid. The emission
      of formaldehyde from furniture materials are more important for the IAQ because
      usually MDF and particleboard of E2 grade are being used as furniture materials
      in Korea.

PMID- 16108905
TI  - Development of a new photocatalytic oxidation air filter for aircraft cabin.
AB  - A new photocatalytic oxidation air filter (PCO unit) has been designed for
      aircraft cabin applications. The PCO unit is designed as a regenerable VOC
      removal system in order to improve the quality of the recirculated air entering
      the aircraft cabin. The PCO was designed to be a modular unit, with four UV lamps
      sandwiched between two interchangeable titanium dioxide coated panels.
      Performances of the PCO unit has been measured in a single pass mode test rig in
      order to show the ability of the unit to decrease the amount of VOCs (toluene,
      ethanol, and acetone) entering it (VOCs are fed separately), and in a multipass
      mode test rig in order to measure the ability of the unit to clean the air of an
      experimental room polluted with the same VOCs (fed separately). Triangular cell
      panels have been chosen instead of the wire mesh panels because they have higher
      efficiency. The efficiency of the PCO unit depends on the type of VOCs that
      challenges it, toluene being the most difficult one to oxidise. The efficiency of
      the PCO unit decreases when the air flow rate increases. The multipass mode test
      results show that the VOCs are oxidized but additional testing time would be
      necessary in order to show if they can be fully oxidized. The intermediate
      reaction products are mainly acetaldehyde and formaldehyde whose amount depends
      on the challenge VOC. The intermediate reaction products are also oxidized and
      additional testing time would be necessary in order to show if they can be fully
      oxidized. The development of this new photocatalytic air filter is still going
      on. PRACTICAL IMPLICATIONS: The VOC/odor removing adsorbers are available for
      only a small proportion of aircraft currently in service. The photocatalytic
      oxidation (PCO) technique has appeared to be a promising solution to odors
      problems met in aircraft. This article reports the test results of a new
      photocatalytic oxidation air filter (PCO unit) designed for aircraft cabin
      applications. The overall efficiency of the PCO unit is function of the compound
      (toluene, ethanol, and acetone) that challenges the unit and toluene appears to
      be the most difficult compound to oxidize. Test results have shown the influence
      of the design of the PCO unit, the air flow rate and the type of UV on the
      efficiency of the PCO unit. The results obtained in this study represent a first
      attempt on the way to design a filter for VOC removal in cabin aircraft
      applications. The PCO technique used by the tested prototype unit is able to
      partially oxidized the challenge VOCs but one has to be aware that some harmful
      intermediate reaction products (mainly formaldehyde and acetaldehyde) are
      produced during the oxidation process before being partially oxidized too.

PMID- 16108906
TI  - Elemental carbon and respirable particulate matter in the indoor air of
      apartments and nursery schools and ambient air in Berlin (Germany).
AB  - This study was performed to examine exposure to typical carcinogenic traffic air
      pollutants in the city center of an urban area. In all, 123 apartments and 74
      nursery schools were analyzed with and without tobacco smoke interference and the
      households in two measuring periods. Simultaneously, the air outside 61 apartment
      windows as well as the average daily traffic volume were measured. Elemental
      carbon (EC), the marker for particulate diesel exhaust and respirable particulate
      matter (RPM) were determined. The thermographic EC analysis was conducted with
      and without prior solvent extraction of the soluble carbon fraction. Comparison
      of these two thermographic EC measurements clearly showed that method-related
      differences in the results, especially for indoor measurements, when high
      background loads of organic material were present (e.g. tobacco smoke), existed.
      Solvent extraction prior to EC determination was therefore appropriate. For the
      first winter measuring period, the EC concentration levels without solvent
      extraction in the indoor air were about 50% higher than those measured in the
      spring/summer period. In the second measuring period (i.e. spring/summer), the
      median EC concentrations after solvent extraction were 1.9 microg/m3 for smokers'
      apartments and 2.1 microg/m3 for non-smokers' apartments, with RPM concentrations
      of 57 and 27 microg/m3, respectively. Nursery schools showed high concentrations
      with median values of 53 microg/m3 for RPM and 2.9 microg/m3 for EC after solvent
      extraction. A significant correlation between the fine dust and EC concentrations
      (after solvent extraction) in the indoor and ambient air was determined. Outdoor
      EC values were also correlated with the average daily traffic volume. The EC
      ratios between indoor and ambient concentration showed a median of 0.8 (range:
      0.3-4.2) in non-smoker households and 0.9 (range: 0.4-1.5) in smoker apartments.
      Furthermore, the EC/RPM ratio in indoor and ambient air was 0.01-0.15 (median
      0.06) and 0.04-0.37 (median 0.09), respectively. PRACTICAL IMPLICATIONS: In the
      absence of indoor sources a significant correlation with regard to respirable
      particulate matter (RPM) and elemental carbon concentrations between the indoor
      and ambient air of apartments was observed. The high degree of certainty
      resulting from this correlation underscores the importance of ambient air
      concentrations for indoor air quality. In nursery schools we found higher
      concentrations of RPM. An explanation of these results could be the high number
      of occupants in the room, their activity and the cleaning intensity.

PMID- 16108907
TI  - Numerical and experimental study of velocity and temperature characteristics in a
      ventilated enclosure with underfloor ventilation systems.
AB  - Airflow and temperature distributions in an enclosure with heat sources
      ventilated by floor supply jets with floor or ceiling air exit vents were
      investigated using experimental and numerical approaches. These ventilation
      configurations represent the floor return or the top return underfloor
      ventilation systems found in real applications. Experiments and numerical
      simulations were performed on a full-sized environmental chamber. The results
      reveal that the temperature stratification in the enclosure highly depended on
      the thermal length scale of the floor supply jets. When the thermal length scale
      of the supply jet was >>1, temperature stratification was minor for all tested
      heat densities and air distribution methods. Significant vertical temperature
      gradients occurred when the jet thermal length scale was <<1. Changes in air
      distribution methods also became significant for temperature stratification at
      small supply jet thermal length scales. Temperature stratification also affected
      the terminal height of the momentum-dominant region of the vertical buoyant
      supply jets. The applicability of these results to underfloor ventilation design
      was also discussed. PRACTICAL IMPLICATIONS: In designing underfloor ventilation
      systems, supply jet conditions and heat load density have to be considered to
      avoid thermal discomfort because of excessive temperature stratifications. This
      study demonstrated, by both numerical simulations and experiments, that thermal
      length scale can be used as a design indicator to predict thermal stratifications
      under a floor return and a top return underfloor ventilation setting.

PMID- 16108908
TI  - Allergens and endotoxin in settled dust from day-care centers and schools in
      Oslo, Norway.
AB  - Allergy to indoor allergens can cause frequent and severe health problems in
      children. Because little is known about the content of allergens in the indoor
      environments in Norway, we wanted to assess the levels of cat, dog and mite
      allergens in schools and day-care centers in Oslo. Allergen levels in dust
      samples from 155 classrooms and 81 day-care units were measured using
      commercially available enzyme-linked immunosorbent assay (ELISA) kits.
      Additionally, we measured the levels of endotoxin in 31 day-care units, using the
      limulus amebocyte lysate test. Most of the dust samples contained detectable
      amounts of cat and dog allergens. In mattress and floor dust (day-care centers),
      and curtain and floor dust (schools) the median Fel d 1 levels were 0.17, 0.002,
      0.02 and 0.079 microg/m2, while the median Can f 1 levels were 1.7, 0.03, 0.1 and
      0.69 microg/m2, respectively. Levels of cat and dog allergens in school floor
      dust were associated with the number of pupils with animals at home. In contrast,
      <1% of the samples had measurable levels of the mite allergen Der p 1. Moreover,
      the levels of endotoxin tended to be higher in dust from floors (1.4 ng/m2)
      compared with that from mattresses (0.9 ng/m2). PRACTICAL IMPLICATIONS: To reduce
      allergen exposure, allergic individuals should be placed in the classes/rooms
      with the fewest pet owners. Moreover, mattresses in day-care centers are major
      reservoirs of cat and dog allergens and should be cleaned frequently.

PMID- 16108909
TI  - Viruses as the causative agent related to 'dampness' and the missing link between
      allergen exposure and onset of allergic disease.
AB  - Asthma and asthma-like symptoms occur more often among people living in humid
      indoor climates. It has been postulated that the higher concentration of
      allergens in these environments is the cause for the increase in the number of
      affected people. However, poor correlations between allergen concentration and
      symptoms indicate a missing link between allergen exposure and onset of asthma.
      Respiratory viruses have been identified in up to 85% cases of asthma or
      exacerbations of asthma. The missing link between respiratory diseases and humid
      indoor climates could therefore be attributed to viruses. The infectious
      effectiveness of respiratory viruses depends strongly on the environment where
      the viruses are spread. For respiratory viruses, survival and infectivity are
      dependent on temperature and relative humidity. A direct link between virus
      induced inflammation and the asthmatogenic process has been proposed. Therefore,
      a more effective spreading of viral infections in damp indoor climates is likely
      to represent the main cause for the increased prevalence of asthma in these
      environments. Moreover, the incidence of viral infections is higher in patients
      with asthma compared with that in control subjects. Therefore, a humid indoor
      climate could also represent a higher risk for persons already sensitized to one
      or more allergens. PRACTICAL IMPLICATIONS: In epidemiological studies where the
      relationship between moisture in the indoor climate, respiratory symptoms and
      exposure to allergens is investigated it will be necessary to analyze the role of
      respiratory viruses in relation to respiratory symptoms. Today, the necessary
      techniques to address the presence of viruses [e.g. polymerase chain reaction
      (PCR), antibodies] are highly sensitive. In order to further our understanding of
      why the frequency of asthma and atopic diseases is still increasing, it is
      mandatory to implement these methods.

PMID- 16108910
TI  - Removal of contaminants released from room surfaces by displacement and mixing
      ventilation: modeling and validation.
AB  - This paper presents the experimental and numerical modeling of contaminant
      dispersion in a full-scale environmental chamber with different room air
      distribution systems. For the experimental modeling, an area source with uniform
      emissions of a hypothetical contaminant (SF6) from the entire floor surface is
      designed and constructed. Two different types of ventilation are studied:
      displacement and mixing ventilation. A computer model for predicting the
      contaminant dispersion in indoor spaces was validated with experimental data. The
      validated model is used to study the effects of airflow and the area-source
      location on contaminant dispersion. Results show that the global airflow pattern
      has a strong impact on the distribution of the contaminants. In general, the
      personal exposure could be estimated by analyzing the relative source positions
      in the airflow pattern. Accordingly, the location of an exhaust diffuser may not
      greatly affect the airflow pattern, but can significantly affect the exposure
      level in the room. PRACTICAL IMPLICATIONS: When designing ventilation in addition
      to bringing fresh air to occupants, it is important to consider the removal of
      contaminants released in the off-gassing of building materials. Typical indoor
      off-gassing examples are emissions of volatile organic compounds from building
      enclosure surfaces such as flooring and painted walls. In this study, we
      conducted experimental and numerical modeling of different area sources in a mock
      up office setup, with displacement or mixing ventilation. Displacement
      ventilation was as successful as mixing ventilation in removing the contaminant
      source from the floor area. Actually, the most important consideration in the
      removal of these contaminants is the relative position of the area source to the
      main airflow pattern and the occupied zone.

PMID- 16108911
TI  - Bacillus anthracis, a story of nature subverted by man.
AB  - Bacillus anthracis is a pathogen of animals which rarely infects humans. Its use
      as a bioweapon has stimulated efforts to develop genetic typing methods and
      therapeutics to respond to an attack. Of particular concern is the transfer of
      virulence genes from B. anthracis to other closely related strains of bacillus.

PMID- 16108912
TI  - Runoff transport of faecal coliforms and phosphorus released from manure in grass
      buffer conditions.
AB  - AIMS: To test the hypothesis that faecal coliform (FC) and phosphorus (P) are
      transported similarly in surface runoff through the vegetative filter strip after
      being released from land-applied manure. METHODS AND RESULTS: The Hagerstown soil
      was packed into boxes that were 10 cm deep, 30 cm wide and 100, 200 or 300 cm
      long. Grass was grown in boxes prior experiments. Same-length boxes were placed
      under rainfall simulator and tilted to have with either 2% or 4% slopes. Dairy
      manure was broadcast on the upper 30-cm section. Rainfall was simulated and
      runoff samples were collected and analysed for Cl, FC and total phosphorus (TP).
      Mass recovery, the concentration decrease rate k, and the ratio FC : TP showed
      that there was a consistent relationship between FC and TP in runoff. CONCLUSION:
      The FC and TP transport through simulated vegetated buffer strips were highly
      correlated. SIGNIFICANCE AND IMPACT OF THE STUDY: As a knowledge base on the
      effect of the environmental parameters on P transport in vegetated buffer strips
      is substantially larger than for manure-borne bacteria, the observed similarity
      may enhance ability to assess the efficiency of the vegetated buffer strips in
      retention of FC currently used as indicator organisms for manure-borne pathogens.

PMID- 16108913
TI  - Isolation and characterization of Shiga toxin-producing Escherichia coli strains
      from raw milk cheeses in France.
AB  - AIMS: To evaluate Shiga toxin-producing Eschericha coli (STEC) prevalence in 1039
      French raw milk cheeses including soft, hard, unripened and blue mould cheeses,
      and to characterize the STEC strains isolated (virulence genes and serotypes).
      METHODS AND RESULTS: STEC strains were recovered from cheese samples by colony
      hybridization. These strains were then serotyped and genetically characterized.
      These strains (32 STEC) were then recovered from 18 of 136 stx-positive samples:
      19 strains had stx2 variant genes stx(2vh-a) (n = 2), stx(2NV206) (n = 2),
      stx(2EDL933) (n = 4) and stx2d (n = 11). Thirty strains had the stx1 gene and one
      strain, the eae gene. Combinations of stx2 and stx1 genes were present in 17
      (81%) of the STEC strains. Nineteen strains belonged to the O6 serogroup and the
      other strains belonged to the O174, O175, O176, O109, O76, O162 and O22
      serogroups in decreasing frequency. CONCLUSIONS: No conclusion can be drawn at
      the moment concerning the potential risk to consumers because the O6:H1 serotype
      has already been found associated with the haemolytic uremic syndrome and almost
      no isolate had the eae gene. SIGNIFICANCE AND IMPACT OF THE STUDY: The large
      number of STEC strains recovered from the cheese samples evaluated in this study
      emphasizes the health risks associated with raw milk cheeses. This further
      emphasizes the immediate need to identify and implement effective pre- and
      postharvest control methods that decrease STEC carriage by dairy cattle and to
      eliminate contamination of their cheeses during processing.

PMID- 16108914
TI  - Plasmid-mediated bioaugmentation of activated sludge bacteria in a sequencing
      batch moving bed reactor using pNB2.
AB  - AIMS: The applicability of plasmid pNB2 for bioaugmentation of bacteria in model
      wastewater treatment reactors receiving 3-chloroaniline (3-CA) was investigated.
      METHODS AND RESULTS: A setup of three biofilm reactors was studied, all initially
      inoculated with bacteria from activated sludge. Reactor PB received a Pseudomonas
      putida pNB2 donor strain not able to degrade 3-CA. Positive control reactor P
      received a 3-CA degrading Comamonas testosteroni pNB2-transconjugant. The
      negative control reactor N remained unchanged. Reactor P showed 3-CA degradation
      from the beginning of the experiment whereas in reactor PB, degradation started
      after an initial lag period. No degradation was observed in reactor N. PCR
      analysis showed that the P. putida donor abundance dropped in reactor PB, whereas
      the plasmid abundance did not, indicating transfer to other bacteria. A number of
      different 3-CA degrading C. testosteroni strains carrying pNB2 could be isolated
      from reactor PB. CONCLUSIONS: A successful plasmid-mediated bioaugmentation was
      achieved with C. testosteroni being the dominant 3-CA degrading pNB2
      transconjugant species active in reactor PB. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The study underlines the potential of gene transfer to contribute to
      establishment and spread of genetic information in general, particularly
      emphasizing the spread of xenobiotic degrading potential by dissemination of
      catabolic genes.

PMID- 16108915
TI  - Accumulation of the compatible solutes, glycine-betaine and ectoine, in osmotic
      stress adaptation and heat shock cross-protection in the biocontrol agent Pantoea
      agglomerans CPA-2.
AB  - AIMS: The effect of modifying the water activity (a(w)) of Pantoea agglomerans
      growth medium with the ionic solute NaCl on water stress resistance, heat-shock
      survival and intracellular accumulation of the compatible solutes glycine-betaine
      and ectoine were determined. METHODS AND RESULTS: The bacterium was cultured in
      an unmodified liquid medium or that modified with NaCl to 0.98 and 0.97 a(w), and
      viability of cells evaluated on a 0.96 a(w)-modified solid media to check water
      stress tolerance. Cells grown under ionic stress had better water stress
      tolerance than control cells. These cells also had cross-protection to heat
      stress (30 min, 45 degrees C). The modified cells accumulated substantial amounts
      of the compatible solutes glycine-betaine and ectoine in contrast to the control
      cells, which contained little or none of these two compounds. CONCLUSIONS:
      Improvement in osmotic and thermal tolerance of cells of the biocontrol agent P.
      agglomerans by modifying growth media with the ionic solute NaCl was achieved.
      The compatible solutes glycine-betaine and ectoine play a critical role in
      environmental stress tolerance improvement. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This approach provides a method for improving the physiological quality of
      inocula and could have implications for formulation and shelf-life of biocontrol
      agents.

PMID- 16108916
TI  - Purification and characterization of extracellular alkaline serine protease from
      Stenotrophomonas maltophilia strain S-1.
AB  - AIMS: The present study was conducted by screening soil bacteria in an attempt to
      isolate a bacterium that produced extracellular alkaline protease, and for
      purification and characterization of the protease. METHODS AND RESULTS: Soil
      bacteria were screened by growth on casein as the sole carbon source.
      Characterization of a strain isolated from soil of Abashiri, Japan indicated a
      taxonomic affiliation to Stenotrophomonas maltophilia, and was named S-1 strain.
      The purified S-1 protease, designed S. maltophilia Protease-1 (SmP-1), exhibited
      an optimal pH of 12.0, optimal reaction temperature of 50 degrees C and a
      molecular mass of approximately 40 kDa by sodium dodecyl sulfate polyacrylamide
      gel electrophoresis (SDS-PAGE). The cleavage sites of the oxidized-insulin B
      chain by SmP-1 were identified as Leu6-Cys7, Cys7-Gly8, Tyr16-Leu17 and Leu17
      Val18. The N-terminal amino acid sequence of the purified alkaline protease was
      determined as NH2-SASAPMVSGVAALVLE. CONCLUSION: A novel extracellular alkaline
      serine protease was isolated from S. maltophilia strain S-1. The optimal pH of
      the proteolytic activity was pH 12.0. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      extremely high optimal pH and heat stability of the alkaline serine protease SmP
      1 might make it widely applicable to food and other industries.

PMID- 16108917
TI  - Pulsed field gel electrophoresis to rapidly detect the presence of IncJ
      conjugative transposon-like elements.
AB  - AIMS: To develop a screening method to detect the presence of the IncJ group of
      integrating conjugative transposon-like elements upon transfer to Escherichia
      coli. METHODS AND RESULTS: The unique insertion site of known IncJ elements, the
      prfC gene, is located in a region of the E. coli chromosome between 98.5 and 100
      min on the E. coli genetic map. Using pulsed field gel electrophoresis and the
      rare cutting restriction enzymes SfiI and XbaI insertions of IncJ elements and an
      estimate of their size could be determined physically. CONCLUSIONS: This method
      allows initial screening of putative IncJ conjugative transposon-like elements by
      physical determination of their integration. SIGNIFICANCE AND IMPACT OF THE
      STUDY: IncJ-like elements, which appear to be highly homologous to the prototype
      IncJ element R391, have been found associated with recent epidemic outbreaks of
      cholera in a number of locations worldwide. Because of their integrative biology
      this method provides the first initial screening method to physically determine
      their presence upon transfer to E. coli.

PMID- 16108918
TI  - Effect of media, temperature and culture conditions on the species population and
      antibiotic resistance of enterococci from broiler chickens.
AB  - AIMS: The effect of media type, incubation temperature and enrichment period on
      the species population and antibiotic susceptibility of enterococci from poultry
      carcass rinsates was determined. METHODS AND RESULTS: Aliquots of rinsates,
      incubated in BBL Enterococcosel broth at 37 degrees C, 42 degrees C, or 45
      degrees C for 24 and 48 h, were inoculated onto BBL Enterococcosel and M
      enterococcus agar. Presumptive positive colonies were identified to species and
      tested for antibiotic resistance. Significant differences (P < or = 0.05) were
      observed for media and temperature. More Enterococcus faecalis were isolated from
      M-enterococcus media and at 37 degrees C while more E. faecium were isolated from
      Enterococcosel agar and at 45 degrees C. The number of antibiotic-resistant E.
      faecalis and E. faecium were also affected by media and temperature. CONCLUSIONS:
      Culture conditions for enterococci affect the observed species and antibiotic
      resistance patterns and therefore should be carefully considered. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study indicates that media and temperature can
      influence the recovery and selection of enterococcal species and antibiotic
      susceptibility.

PMID- 16108919
TI  - Purification and partial chemical characterization of the antimicrobial peptide
      cerein 8A.
AB  - AIMS: To purify and to characterize the antimicrobial compound cerein 8A. METHODS
      AND RESULTS: Cerein 8A was isolated by ammonium sulfate precipitation, 1-butanol
      extraction and ion-exchange chromatography. Direct activity on sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was observed. The purified
      substance corresponded to a 26 kDa peptide band. The native protein eluted at the
      void volume of Sephadex G-100, but within the included volume when a 1.5 mol l(
      1) NaCl buffer was used, indicating that cerein 8A aggregates extracellularly.
      The antimicrobial activity was lost by treatment with proteases and heat. The
      ultraviolet spectrum was typical of a polypeptide and the infrared spectrum
      indicates that the peptide contains acyl group(s) in its structure. Intact
      Bacillus cereus spores were sensitive to cerein 8A at 1600 AU ml(-1).
      CONCLUSIONS: Cerein 8A show distinct properties from other antimicrobial peptides
      of B. cereus, and has a significant inhibitory effect on spores. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The characterization of a substance active against important
      pathogens addresses an important aspect of food safety.

PMID- 16108920
TI  - Inhibition of bacteriophage K proliferation on Staphylococcus aureus in raw
      bovine milk.
AB  - AIMS: To assess the ability of staphylococcal bacteriophage K to inhibit
      Staphylococcus aureus in raw milk. METHODS AND RESULTS: The ability of
      bacteriophage (phage) to replicate in milk is important in situations where phage
      might be used as a therapeutic for bovine mastitis. Phage K was able to replicate
      normally, leading to elimination of the host culture in milk, which had been
      previously heat-treated. When raw milk was used under identical conditions, the
      phages were unable to replicate. Phage adsorption assays were performed and these
      demonstrated that adsorption of phage was significantly reduced in the raw milk
      while it was restored in the heat-treated sample (86.50% compared with 99.96%
      adsorption respectively). When confocal microscopy with a Live/Dead Bac light
      staining system was employed, it was observed that in raw milk S. aureus formed
      clusters associated with fat globules, while in heat-treated milk, bacterial
      agglutination had not occurred. CONCLUSIONS: Raw milk inhibits staphylococcal
      phage K proliferation. SIGNIFICANCE AND IMPACT OF THE STUDY: This observation has
      implications for the exploitation of staphylococcal therapeutic phage in milk.

PMID- 16108921
TI  - No association between partial depopulation and Campylobacter spp. colonization
      of Dutch broiler flocks.
AB  - AIMS: To determine whether an association exists between partial depopulation of
      a flock and increased Campylobacter colonization in that flock. METHODS AND
      RESULTS: Data from 1737 flocks of two Dutch integrators were used. Flocks that
      experienced partial depopulation were defined as 'exposed' and those that did not
      as 'nonexposed'. Multivariable modelling was accomplished with, in addition to
      'exposure', the independent variables 'age of broilers at slaughter' and 'season'
      to adjust for possible confounding. The response variable was 'Campylobacter
      colonization'. The odds ratio (OR) for partial depopulation for integrator A was
      0.8 [95% CI (0.4, 1.8)]; for integrator B the OR = 0.8 [95% CI (0.5, 1.3)]. Age
      and season were confounders: the difference in Campylobacter status between
      exposed and nonexposed flocks of integrator A could be explained by both
      variables; for integrator B, only season was associated with Campylobacter
      status. CONCLUSIONS: We found no significant association between partial
      depopulation and an increased risk of Campylobacter colonization among broiler
      flocks at final depopulation. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      demonstrates that Campylobacter colonization in a broiler flock is not influenced
      by the partial depopulation of that flock.

PMID- 16108922
TI  - Gaining electricity from in situ oxidation of hydrogen produced by fermentative
      cellulose degradation.
AB  - AIM: To exploit the fermentative hydrogen generation and direct hydrogen
      oxidation for the generation of electric current from the degradation of
      cellulose. METHODS AND RESULTS: Utilizing the metabolic activity of the
      mesophilic anaerobe Clostridium cellulolyticum and the thermophilic Clostridium
      thermocellum we show that electricity generation is possible from cellulose
      fermentation. The current generation is based on an in situ oxidation of
      microbially synthesized hydrogen at platinum-poly(tetrafluoroaniline) (Pt-PTFA)
      composite electrodes. Current densities of 130 mA l(-1) (with 3 g cellulose per
      litre medium) were achieved in poised potential experiments under batch and semi
      batch conditions. CONCLUSIONS: The presented results show that electricity
      generation is possible by the in situ oxidation of hydrogen, product of the
      anaerobic degradation of cellulose by cellulolytic bacteria. SIGNIFICANCE AND
      IMPACT OF THE STUDY: For the first time, it is shown that an insoluble complex
      carbohydrate like cellulose can be used for electricity generation in a microbial
      fuel cell. The concept represents a first step to the utilization of
      macromolecular biomass components for microbial electricity generation.

PMID- 16108923
TI  - Screening of benzalkonium chloride resistance in Listeria monocytogenes strains
      isolated during cold smoked fish production.
AB  - AIMS: To determine the susceptibility to disinfectants and cross-resistance to
      antibiotics in Listeria monocytogenes strains isolated from fish products and the
      fish-processing environment. METHODS AND RESULTS: Minimal inhibitory
      concentration assessment, using the agar dilution method, showed 108 of 255 L.
      monocytogenes isolates with low susceptibility to benzalkonium chloride (BC),
      commonly used in food industries. Most of them are from raw products of farmed
      fish during processing, while the remaining resistant isolates were mainly from
      the environment and finished products irrespective of the fish species. Two BC
      resistant isolates were resistant to ethidium bromide (EB). The conservation of
      resistance after plasmid curing suggested that the resistance genes are not
      plasmid associated. EB accumulation assays demonstrated that the two BC(R) EB(R)
      isolates used an efflux pump to expel these substrates whereas a different
      mechanism was probably used by the majority of the strains with BC(R) EB(S)
      pattern. No cross-resistance was found with antibiotics. CONCLUSIONS: This study
      highlights the difference in susceptibilities to BC for L. monocytogenes strains
      isolated from fish-processing plants and in resistance mechanisms to BC developed
      by these bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of BC
      resistant L. monocytogenes strains could contribute to their adaptation and so
      explained their survival and persistence in the fish-processing environment.

PMID- 16108924
TI  - Functional incidental training: a randomized, controlled, crossover trial in
      Veterans Affairs nursing homes.
AB  - OBJECTIVES: To test the effects of a rehabilitative intervention directed at
      continence, mobility, endurance, and strength (Functional Incidental Training
      (FIT)) in older patients in Department of Veterans Affairs (VA) nursing homes.
      DESIGN: Randomized, controlled, crossover trial. SETTING: Four VA nursing homes.
      PARTICIPANTS: All 528 patients in the nursing homes were screened; 178 were
      eligible, and 107 were randomized to an immediate intervention group (Group 1;
      n=52) and a delayed intervention group (Group 2; n=55). INTERVENTION: Trained
      research staff provided the FIT intervention, which included prompted voiding
      combined with individualized, functionally oriented endurance and strength
      training exercises offered four times per day, 5 days per week, for 8 weeks.
      Group 1 received the intervention while Group 2 served as a control group; then
      Group 2 received the intervention while Group 1 crossed over to no intervention.
      A total of 64 subjects completed the intervention phase of the trial.
      MEASUREMENTS: Timed measures of walking or wheeling a wheelchair (mobility), sit
      to-stand exercises, independence in locomotion and toileting as assessed using
      the Functional Independence Measure (FIM), one-repetition maximum weight for
      several measures of upper and lower body strength, frequency of urine and stool
      incontinence, and appropriate toileting ratios. RESULTS: There was a significant
      effect of the FIT intervention on virtually all measures of endurance, strength,
      and urinary incontinence but not on the FIM for locomotion or toileting. The
      effects of FIT were observed when Group 1 received the intervention and was
      compared with the control group and when Group 2 crossed over to the
      intervention. Group 1 deteriorated in all measures during the 8-week crossover
      period. Within-person comparisons also demonstrated significant effects on all
      measures in the 64 participants who completed the intervention; 43 (67%) of these
      participants were "responders" based on maintenance or improvement in at least
      one measure of endurance, strength, and urinary incontinence. No adverse events
      related to FIT occurred during the study period. CONCLUSION: FIT improves
      endurance, strength, and urinary incontinence in older patients residing in VA
      nursing homes. Translating these positive benefits achieved under research
      conditions into practice will be challenging because of the implications of the
      intervention for staff workload and thereby the costs of care.

PMID- 16108925
TI  - Dementia and Alzheimer's disease incidence in relationship to cardiovascular
      disease in the Cardiovascular Health Study cohort.
AB  - OBJECTIVES: To determine whether coronary artery disease, peripheral arterial
      disease (PAD), or noninvasive markers of cardiovascular disease (CVD) predict the
      onset of dementia and Alzheimer's disease (AD). DESIGN: Longitudinal cohort
      study. SETTING: Four U.S. communities. PARTICIPANTS: Men and women (N=3,602) with
      a brain magnetic resonance imaging (MRI) scan but no dementia were followed for
      5.4 years. Participants with stroke were excluded. MEASUREMENTS: Neurologists and
      psychiatrists classified incident cases of dementia and subtype using
      neuropsychological tests, examination, medical records and informant interviews.
      CVD was defined at the time of the MRI scan. Noninvasive tests of CVD were
      assessed within 1 year of the MRI. Apolipoprotein E allele status, age, race,
      sex, education, Mini-Mental State Examination score, and income were assessed as
      potential confounders. RESULTS: The incidence of dementia was higher in those
      with prevalent CVD, particularly in the subgroup with PAD. The rate of AD was
      34.4 per 1,000 person-years for those with a history of CVD, versus 22.2 per
      1,000 person-years without a history of CVD (adjusted hazard ratio (HR)=1.3, 95%
      confidence interval (CI)=1.0-1.7). Rates of AD were highest in those with PAD
      (57.4 vs 23.7 per 100 person-years, adjusted HR=2.4, 95% CI=1.4-4.2). Results
      were similar with further exclusion of those with vascular dementia from the AD
      group. A gradient of increasing risk was noted with the extent of vascular
      disease. CONCLUSION: Older adults with CVD other than stroke had a higher risk of
      dementia and AD than did those without CVD. The risk was highest in people with
      PAD, suggesting that extensive peripheral atherosclerosis is a risk factor for
      AD.

PMID- 16108926
TI  - Hospitalization for pneumonia in the Cardiovascular Health Study: incidence,
      mortality, and influence on longer-term survival.
AB  - OBJECTIVES: To estimate the rate of hospitalization for pneumonia in community
      dwelling older adults and to assess its risk factors and contribution to
      mortality. DESIGN: Prospective observational study. SETTING: The Cardiovascular
      Health Study (CHS) in four U.S. communities. PARTICIPANTS: Five thousand eight
      hundred eighty-eight men and women aged 65 and older who were followed for a
      median 10.7 years. MEASUREMENTS: Participants were interviewed about medical
      history and demographics; evaluated for lung, physical, and cognitive function;
      and followed for hospitalizations, cardiovascular disease, and death. RESULTS:
      Nearly 10% of the cohort was hospitalized for pneumonia, for a rate of 11.1 per
      1,000 person-years (95% confidence interval (CI)=10.2-12.0). Risk factors
      included older age, male sex, current and past smoking, poor physical and lung
      function, and history of cardiovascular disease and chronic obstructive pulmonary
      disease. Ten percent of participants died during their incident pneumonia
      hospitalization, and death rates were high in those who survived to discharge.
      Compared with participants who had not been hospitalized for pneumonia, the
      relative risk of total mortality was 4.9 (95% CI=4.1-6.0) during the first year
      after hospitalization and 2.6 (95% CI=2.2-3.1) thereafter, adjusted for age, sex,
      and race. The respective relative risks were 3.9 (95% CI=3.1-4.8) and 2.0 (95%
      CI=1.6-2.4) after further adjustment for baseline history of cardiovascular
      disease; diabetes mellitus; smoking; and measures of lung, physical, and
      cognitive function. CONCLUSION: In older people, hospitalization for pneumonia is
      common and is associated with an elevated risk of death, as shown in this
      population-based, prospective cohort.

PMID- 16108927
TI  - Benchmarks for antibiotic use and cost in long-term care.
AB  - OBJECTIVES: To evaluate previously described antibiotic use and cost indicators
      in community nursing homes to determine whether they may be useful as benchmarks
      and to evaluate the association between functional status, infection occurrence,
      and antibiotic use. DESIGN: Retrospective observational study. SETTING: Eleven
      proprietary long-term care facilities owned by one company. PARTICIPANTS: Only
      facility-specific cumulative data were used. MEASUREMENTS: Antibiotic use and
      cost indicators (incidence of antibiotic use, antibiotic utilization ratio, cost
      of antibiotics per resident care day (RCD), and cost per antibiotic day),
      infection rates, and functional status as measured using the case-mix index (CMI)
      of the Resource Utilization Groups II system. Mean yearly values for each measure
      were calculated for each facility. RESULTS: There was significant variation in
      all of the antibiotic indicators between the 11 nursing homes, but there was no
      correlation between mean facility CMI and infection rate. However, there was a
      trend toward a significant correlation between mean facility CMI and mean
      facility incidence of antibiotic use, antibiotic utilization rate, and cost per
      RCD. Variation in mean facility infection rate explained 66% of the variation in
      mean facility incidence of antibiotic use (P<.001). In a multivariate analysis,
      mean facility infection rate (P=.003) and mean facility CMI (P=.046) were
      predictors of mean incidence of antibiotic use and explained 83% of the variation
      in dependent variable. CONCLUSION: The significant variation in mean antibiotic
      use and cost indicators between the 11 study facilities suggests that these
      indicators may be useful as benchmarks for quality-improvement efforts. For the
      first time, objective evidence is provided demonstrating the influence of
      functional status on antibiotic use in the nursing home setting.

PMID- 16108928
TI  - Elder financial abuse: an evaluation framework and supporting evidence.
AB  - OBJECTIVES: To develop a valid and reliable framework for evaluating cases of
      alleged elder financial abuse. DESIGN: Experienced experts in elder financial
      abuse rated a framework with eight elements. SETTING: Professionals attending an
      advanced training course on elder abuse. PARTICIPANTS: Deputy district attorneys
      (n=44), senior law enforcement detectives (n=59), Adult Protective Service
      workers, and public guardians and victim advocates (n=56) who had a combined
      total of 1,985 years of experience and who had investigated a total of 3,225
      cases (mean of 13.1 years and 21.2 cases) were included. MEASUREMENTS: These
      experienced professionals were asked to rate how well an evaluative framework
      matched their experience with elder financial abuse using a 5-point rating scale
      ranging from very little to almost entirely. RESULTS: The mean rating for the
      model was 4.4 out of 5. About 90% of the sample rated it as almost entirely or
      very much matching their experience. There were no differences between
      professions. The reliability measure was 0.85. CONCLUSION: These results suggest
      a reliable and valid framework for evaluating cases of possible elder financial
      abuse.

PMID- 16108929
TI  - Are older people dying of depression? Findings from the Medical Research Council
      trial of the assessment and management of older people in the community.
AB  - OBJECTIVES: To examine the relationship between symptoms of depression and
      mortality in older people. DESIGN: Prospective longitudinal study. SETTING: Fifty
      three general practices in the United Kingdom. PARTICIPANTS: Thirteen thousand
      ninety-seven people aged 75 and older participating in the Medical Research
      Council Trial of the Assessment and Management of Older People in the Community.
      MEASUREMENTS: Depression was measured using the 15-item Geriatric Depression
      Scale (GDS-15); the main outcome was all-cause mortality. RESULTS: Morbidity,
      disability, and lifestyle factors can explain most of the observed relationship
      between symptoms of depression and mortality (hazard ratio=1.75, 95% confidence
      interval (CI)=1.53-1.99), but after mutual adjustment for these factors, subjects
      who reported six or more symptoms of depression on the GDS-15 were still 27% more
      likely to have died by the end of the follow-up period than those below the
      threshold for depression (95% CI=1.11-1.45). CONCLUSION: The findings from this
      study suggest that depression confers a small risk for mortality in older people,
      not explained solely by poor health. The results support the encouragement of
      effective diagnosis, treatment, and support for individuals with depression as
      highlighted by the World Health Organization and the UK National Service
      Framework for older people.

PMID- 16108930
TI  - Skilled care requirements for elderly patients after coronary artery bypass
      grafting.
AB  - OBJECTIVES: To examine the extent to which elderly individuals use various
      skilled care facilities after coronary artery bypass grafting (CABG). DESIGN:
      Retrospective cohort study. SETTING: State of Michigan from 1997 to 1998.
      PARTICIPANTS: Residents aged 65 and older enrolled in Medicare who underwent
      CABG. MEASUREMENTS: Cumulative incidence of admission within 100 days of hospital
      discharge, relative risk (RR) of admission, readmission or extended stay at a
      skilled care facility, and length of stay in a skilled care facility. RESULTS:
      Fifty percent of patients aged 80 and older used a skilled care facility after
      CABG, with most requiring admission to a skilled nursing facility (SNF) or
      readmission to an acute-care hospital within 100 days after discharge. Patients
      aged 80 and older had a significantly higher risk of admission to a SNF (adjusted
      RR=3.3, 95% confidence interval (CI)=2.8-4.0) than did those aged 65 to 69, as
      did patients aged 75 to 79 (adjusted RR=2.2, 95% CI=1.8-2.6) and those aged 70 to
      74 (adjusted RR=1.5, 95% CI=1.3-1.8). The length of time spent in skilled care
      facilities significantly increased with age (mean days=13.3 for aged 65-69, 16.9
      for 70-74, 19.6 for 75-79, and 22.9 for 80 and older; P<.001). CONCLUSION: Older
      patients are more likely to be admitted to a SNF, be readmitted to an acute-care
      hospital, and have longer institutional stays after CABG. When balancing the
      risks and benefits of CABG, physicians, patients, families, and policy-makers
      need to carefully consider the likelihood of follow-up institutional care in
      elderly patients.

PMID- 16108931
TI  - Physicians' experiences with demented patients with advance euthanasia directives
      in the Netherlands.
AB  - OBJECTIVES: To estimate the incidence of (compliance with) advance euthanasia
      directives of patients suffering from dementia in the Netherlands and to gain
      knowledge about the experiences of physicians. DESIGN: Retrospective interview
      study. SETTING: Physicians in the Netherlands. PARTICIPANTS: Four hundred ten
      physicians. MEASUREMENTS: Physicians were interviewed about their demented
      patients who had an advance euthanasia directive. Nursing home physicians were
      interviewed more extensively. RESULTS: Approximately 2,200 demented patients with
      an advance euthanasia directive die annually after being treated by a physician
      who knows about this directive. In 76% of such cases, compliance with the
      directive was discussed, but euthanasia was seldom performed. In two-thirds of
      the cases of demented nursing home patients with an advance euthanasia directive,
      the physician was able to identify during the course of the disease a situation
      for which the patient had intended the directive. One-quarter of the nursing home
      physicians thought that their most recent patient suffered unbearably to a (very)
      high degree, and half of them thought that the patient suffered hopelessly to a
      (very) high degree. In three-quarters of the cases, the relatives did not want
      the nursing home physician to comply with the directive, but they did want to
      respect the patient's wishes by forgoing life-prolonging treatment, which
      occurred in approximately 90% of cases. CONCLUSION: Most nursing home physicians
      think that the suffering of patients with dementia can be unbearable and hopeless
      as a consequence of dementia, but most physicians do not consider dementia to be
      grounds for euthanasia, unless perhaps the patient has an additional illness.

PMID- 16108932
TI  - End-of-life care in black and white: race matters for medical care of dying
      patients and their families.
AB  - OBJECTIVES: To compare the end-of-life medical care experienced by African
      American and white decedents and their families. DESIGN: Cross-sectional,
      retrospective survey with weighted results based on a two-stage probability
      sampling design. SETTING: Hospitals, nursing homes, and home-based medical
      services across the United States. PARTICIPANTS: Surrogates (N=1,447; primarily
      family members) for decedents from 22 states. MEASUREMENTS: Validated end-of-life
      care outcomes concerning symptom management, decision-making, informing and
      supporting families, individualized care, coordination, service utilization, and
      financial impact. RESULTS: Family members of African-American decedents were less
      likely than those of white decedents to rate the care received as excellent or
      very good (odds ratio (OR)=0.4). They were more likely to report absent (OR=2.4)
      or problematic (OR=1.9) physician communication, concerns with being informed
      (OR=2.5), and concerns with family support (OR=2.6). Family members of African
      Americans were less likely than those of whites to report that the decedent had
      treatment wishes (OR=0.3) or written advance care planning documents (OR=0.4).
      These differences persist when limiting the sample to respondents whose
      expectations for life-sustaining treatments matched treatments received. Family
      members of African-American decedents also were more likely to report financial
      hardship due to savings depletion (OR=2.1) or difficulty paying for care (OR=2.0)
      and that family/friends (OR=2.0) or home health workers (OR=1.9) provided home
      care. CONCLUSION: This national study brings evidence that racial disparities
      persist into end-of-life care, particularly regarding communication and family
      needs. Results also suggest different home care patterns and levels of financial
      impact.

PMID- 16108934
TI  - Relationship between patient age and duration of physician visit in ambulatory
      setting: does one size fit all?
AB  - OBJECTIVES: To determine whether patient age, the presence of comorbid illness,
      and the number of prescribed medications influence the duration of a physician
      visit in an ambulatory care setting. DESIGN: A cross-sectional study of
      ambulatory care visits made by adults aged 45 and older to primary care
      physicians. SETTING: A probability sample of outpatient follow-up visits in the
      United States using the National Ambulatory Medical Care Survey (NAMCS) 2002
      database. PARTICIPANTS: Of 28,738 physician visits in the 2002 NAMCS data set,
      there were 3,819 visits by adults aged 45 and older included in this study for
      analysis. MEASUREMENTS: The primary endpoint was the time that a physician spent
      with a patient at each visit. Covariates included for analyses were patient
      characteristics, physician characteristics, visit characteristics, and source of
      payment. Visit characteristics, including the number of diagnoses and the number
      of prescribed medications, the major diagnoses, and the therapeutic class of
      prescribed medications, were compared for different age groups (45-64, 65-74, and
      > or =75) to determine the complexity of the patient's medical conditions.
      Endpoint estimates were computed by age group and were also estimated based on
      study covariates using univariate and multivariate linear regression. RESULTS:
      The mean time+/-standard deviation spent with a physician was 17.9+/-8.5 minutes.
      There were no differences in the duration of visits between the age groups before
      or after adjustment for patient covariates. Patients aged 75 and older had more
      comorbid illness and were prescribed more medications than patients aged 45 to 64
      and 65 to 74 (P<.001). Patients aged 75 and older were also prescribed more
      medications that require specific monitoring and counseling (warfarin, digoxin,
      angiotensin-converting enzyme inhibitors, diuretics, and levothyroxine) than were
      patients in other age groups (P<.001). Hypertension, coronary artery disease,
      atrial fibrillation, congestive heart failure, cerebrovascular disease, and
      transient ischemic attack were more common in patients aged 75 and older than in
      other age groups (P<.001). Despite these differences, there were no differences
      in unadjusted or adjusted duration of physician visit between the age groups.
      CONCLUSION: Although patients aged 75 and older had more medical conditions and
      were at higher risk for drug-related problems than younger patients, the duration
      of physician visits was similar across the age groups. These findings suggest
      that elderly patients may require a multidisciplinary approach to optimize
      patient care in the ambulatory setting.

PMID- 16108933
TI  - Effect of blood pressure and diabetes mellitus on cognitive and physical
      functions in older adults: a longitudinal analysis of the advanced cognitive
      training for independent and vital elderly cohort.
AB  - OBJECTIVES: To evaluate the effect of blood pressure (BP) and diabetes mellitus
      (DM) on cognitive and physical performance in older, independent-living adults.
      DESIGN: Longitudinal study with secondary data analysis from the Advanced
      Cognitive Training for Independent and Vital Elderly randomized intervention
      trial. SETTING: Six field sites in the United States. PARTICIPANTS: Two thousand
      eight hundred two independent-living subjects aged 65 to 94. MEASUREMENTS:
      Cognitive functions in different domains and physical functions measured using
      activities of daily living, instrumental activities of daily living (IADLs), and
      the physical function subscale from the Medical Outcomes Study Short Form-36 (SF
      36) Health Survey. RESULTS: After the first annual examination, hypertension was
      associated with a faster decline in performance on logical reasoning tasks
      (ability to solve problems following a serial pattern), whereas DM was associated
      with accelerated decline on the Digit Symbol Substitution Test (speed of
      processing). The reasoning and Digit Symbol Substitution test are executive
      function tasks thought to be related to frontal-lobe function. Hypertension and
      DM were associated with a significantly faster pace of decline on the SF-36
      physical function component score. Individuals with DM had a faster pace of
      decline in IADL functioning than nondiabetic subjects. There was no evidence for
      an interaction between BP and DM on cognitive or physical function decline.
      CONCLUSION: Hypertension and DM are associated with accelerated decline in
      executive measures and physical function in independent-living elderly subjects.
      Further research is needed to determine whether cardiovascular risk modification
      ameliorates cognitive and functional decline in elderly people.

PMID- 16108935
TI  - Reduction in fear of falling through intense tai chi exercise training in older,
      transitionally frail adults.
AB  - OBJECTIVES: To determine whether an intense tai chi exercise program could reduce
      fear of falling better than a wellness education (WE) program in older adults who
      had fallen previously and meet criteria for transitioning to frailty. DESIGN:
      Cluster-randomized, controlled trial of 48 weeks' duration. SETTING: Ten matched
      pairs of congregate living facilities in the greater Atlanta area. PARTICIPANTS:
      Sample of 291 women and 20 men, aged 70 to 97. MEASUREMENTS: Activity-related
      fear of falling using the Activities-Specific Balance Confidence Scale (ABC) and
      the Fall Efficacy Scale at baseline and every 4 months for 1 year. Demographics,
      time to first fall and all subsequent falls, functional measures, Centers for
      Epidemiologic Studies Depression Scale, medication use, level of physical
      activity, comorbidities, and adherence to interventions. RESULTS: Mean ABC was
      similar in both cohort groups at the time of randomization but became
      significantly higher (decreased fear) in the tai chi cohort at 8 months (57.9 vs
      49.0, P<.001) and at study end (59.2 vs 47.9, P<.001). After adjusting for
      covariates, the mean ABC after 12 months of intervention was significantly
      greater in the tai chi group than in the WE group, with the differences
      increasing with time (mean difference at 12 months=9.5 points, 95% confidence
      interval=4.8-14.2, P<.001). CONCLUSION: Tai chi led to a significantly greater
      reduction in fear of falling than a WE program in transitionally frail older
      adults. The mean percentage change in ABC scores widened between tai chi and WE
      participants over the trial period. Tai chi should be considered in any program
      designed to reduce falling and fear of falling in transitionally frail older
      adults.

PMID- 16108937
TI  - Associations between dementia/mild cognitive impairment and cognitive performance
      and activity levels in youth.
AB  - OBJECTIVES: To study the associations between dementia/mild cognitive impairment
      (MCI) and cognitive performance and activity levels in youth. DESIGN:
      Retrospective cohort study. SETTING: Research volunteers living throughout the
      United States. PARTICIPANTS: A total of 396 persons (mean age 75) who were
      graduates of the same high school in the mid-1940s. MEASUREMENTS: Adolescent
      intelligence quotient (IQ) scores were gathered from archived student records,
      and activity levels were determined from yearbooks. A two-stage telephone
      screening procedure (Modified Telephone Interview for Cognitive Status or
      Informant Questionnaire on Cognitive Decline in the Elderly followed by Dementia
      Questionnaire) was used to determine adult cognitive status. Data were analyzed
      using logistic regression to model the risk of cognitive impairment
      (dementia/MCI) versus no cognitive impairment as a function of IQ and activity
      level, adjusting for sex and education. RESULTS: High adolescent IQ and greater
      activity level were each independently associated with a lower risk for
      dementia/MCI (odds ratio (OR) for a 1-standard deviation increase in IQ=0.51, 95%
      confidence interval (CI)=0.32-0.79; OR for a unit increase in activity=0.32, 95%
      CI=0.12-0.84). No association was found between sex or education and adult
      cognitive status in this model. CONCLUSION: High IQ and greater activity levels
      in youth reduce the risk for cognitive impairments in aging. The mechanism(s)
      underlying these associations are unknown, but intelligence may be a marker for
      cognitive/neurological "reserve," and involvement in activities may contribute to
      "reserve." Early neuropathology and ascertainment bias are also possible
      explanations for the observed associations.

PMID- 16108936
TI  - Impaired vision and the ability to take medications.
AB  - OBJECTIVES: To assess relationships between vision (contrast sensitivity,
      stereopsis, visual acuity) and a performance-based measure of ability to
      implement new medications. DESIGN: Cross-sectional analysis; prospective cohort
      study. SETTING: Community-based. PARTICIPANTS: Three hundred thirty-five
      participants aged 73 to 82 in Year 3 of the Women's Health and Aging Study II, a
      representative sample of the two-thirds least-disabled community-dwelling women.
      MEASUREMENTS: Hopkins Medication Schedule Pillbox Ratio, a joint measure of
      accuracy and time, and a performance-based measure of ability to implement a
      prescription. Participants received written and verbal instructions for taking
      two medications and were directed to place pills in a pillbox accordingly. Vision
      assessments: contrast sensitivity (Pelli-Robson letter sensitivity chart),
      stereopsis (Randot Circles), and visual acuity (Early Treatment Diabetic
      Retinopathy Study eye chart). RESULTS: Forty-four percent (148/335) of women
      incorrectly placed one or both medications. Each vision measure was positively
      associated with Pillbox Ratio scores and varied with cognition and time to
      completion. Better visual acuity, contrast sensitivity, and stereopsis were each
      associated with better performance in women with poor cognition who filled the
      pillbox quickly. Additionally, better visual acuity was associated with better
      performance in participants with good cognition who filled the pillbox slowly;
      better stereopsis was associated with better performance in participants with
      poor cognition who filled the pillbox slowly and whose stereoacuity was below
      normal. CONCLUSION: Visual acuity, contrast sensitivity, and stereopsis should be
      considered potential risk factors for impaired ability to implement a medication
      regimen in older adults. Future research should investigate the role of vision,
      including contrast sensitivity and stereopsis, on performance of other
      instrumental activities of daily living.

PMID- 16108938
TI  - Predictors of combined cognitive and physical decline.
AB  - OBJECTIVES: To determine the incidence and correlates of combined declines in
      cognitive and physical performance. DESIGN: Cohort study of community-dwelling
      older women with moderate to severe disability. SETTING: The community
      surrounding Baltimore, Maryland. PARTICIPANTS: Participants in the Women's Health
      and Aging Study I with Mini-Mental State Examination (MMSE) score or 24 or
      greater and walking speed greater than 0.4 m/s at baseline. MEASUREMENTS:
      Cognitive decline was defined as an MMSE score less than 24 and physical decline
      as a walking speed of 0.4 m/s or less in at least one of the three annual follow
      up visits. Participants were stratified into groups based on cognitive or
      physical decline or both. Group characteristics were compared, and results were
      adjusted for age, race, education, and significant covariates. RESULTS: Of 558
      women that met the baseline MMSE and walking speed inclusion criteria, 21%
      developed physical decline, 12% developed cognitive decline, and 11% experienced
      combined cognitive and physical decline. After adjustment, physical decline was
      associated with age, nonwhite race, former smoking, baseline walking speed, and
      instrumental activities of daily living (IADL) impairment. Cognitive decline was
      associated with age and baseline MMSE score. Combined decline was associated with
      age, baseline walking speed, MMSE score, IADL impairment, as well as current
      smoking (odds ratio (OR)=5.66, 95% confidence interval (CI)=1.49-21.54) and
      hemoglobin level (OR=0.68, 95% CI=0.47-0.98). CONCLUSION: Potential predictors of
      cognitive and physical performance decline were identified. The association
      between smoking and lower hemoglobin levels and combined cognitive and physical
      decline may represent potentially modifiable risk factors and should be confirmed
      in future studies.

PMID- 16108939
TI  - Community-acquired thoracic empyema in older people.
AB  - OBJECTIVES: To compare the clinical characteristics of community-acquired
      thoracic empyema in older and younger patients and to analyze the effect of
      various factors on outcome. DESIGN: A retrospective, comparative observational
      study. SETTING: A university-affiliated tertiary medical center. PARTICIPANTS:
      Forty-six patients aged 65 and older (older group) and 86 patients aged 18 to 64
      (younger group). MEASUREMENTS: Demographic, clinical, and microbiological data
      were reviewed. RESULTS: Older patients were more likely to have dyspnea but less
      likely to have chest pain or fever (P<.05 for all). The causative organisms were
      similar between the two groups, with anaerobes and facultative streptococci the
      most common pathogens. Older patients had increased morbidity and longer hospital
      stay (median 29.5 vs 20 days, P<.001), but the in-hospital mortality was not
      significantly different between the two groups (13% vs 8%, P=.37). Multivariate
      analysis showed that coexisting malignancy (odds ratio (OR)=10.33, P=.01), lack
      of fever higher than 38 degrees C (OR=17.97, P=.03), and isolation of fungi from
      pleural fluid (OR=32.66, P=.01) were independently and significantly associated
      with in-hospital deaths. CONCLUSION: The microbiology and mortality of community
      acquired thoracic empyema were similar between the two age groups. Difference in
      chronological age did not explain in-hospital death. This finding highlights the
      importance of effective treatment to obtain better outcomes for older patients.

PMID- 16108940
TI  - Septic arthritis in patients aged 80 and older: a comparison with younger adults.
AB  - OBJECTIVES: To compare the frequency and characteristics of septic arthritis in
      patients younger than 80 and aged 80 and older. DESIGN: Retrospective. SETTING:
      Single hospital center. PARTICIPANTS: Patients admitted between 1979 and 2002 for
      septic arthritis. MEASUREMENTS: Age, sex, time to diagnosis, predisposing
      factors, joint, temperature, white blood cell count, microorganism, and short
      term outcome. RESULTS: Of 335 patients, 206 (61.4%) were aged 60 and older, and
      42 (12.5%) were 80 and older. The latter had an average age of 84 (range 80-97)
      and were mainly women (72%). Eighteen of the 42 had at least one risk factor. The
      mean time to diagnosis was 21 days (range 1 day to 3 months). Twenty patients
      (47%) had knee involvement, six (14%) shoulder involvement, ten (23.8%) a
      prosthetic infection, and five (12%) polyarticular infection. Ten (23%) were
      afebrile. In half of the cases, there was no increase in white blood cell count.
      The microorganisms isolated were Staphylococcus aureus (n=16, 38%), coagulase
      negative staphylococci (n=8, 19%), streptococci (n=12, 28%), and gram-negative
      bacilli (n=6, 14%). The mortality rate increased with age: 0.7% of patients
      younger than 60, 4.8% of those aged 60 to 79, and 9.5% of those aged 80 and
      older. CONCLUSION: Advanced age is a risk factor for septic arthritis and poor
      outcome.

PMID- 16108941
TI  - Do age and comorbidity affect intensity of pharmacological therapy for poorly
      controlled diabetes mellitus?
AB  - OBJECTIVES: To examine the influence of age and comorbidity on intensification of
      medical therapy for patients with poorly controlled diabetes mellitus (DM).
      DESIGN: Observational cohort study using data from Department of Veterans Affairs
      (VA) national databases. SETTING: Thirteen VA medical centers in New England,
      Florida, and Puerto Rico. PARTICIPANTS: Veterans (N=5,317) with poorly controlled
      DM receiving regular medical care MEASUREMENTS: An increase in hypoglycemic
      medications, or intensification of therapy, was considered present at the visit
      if a new hypoglycemic medication was started or the dosage of an existing
      medication was increased. RESULTS: The overall rate of intensification of therapy
      was 20.8% (1,106/5,317). The rate of intensification was highest in the youngest
      patients without comorbidity (24.5%) and lowest in the oldest patients with
      comorbidity (15.7%) (P<.001). CONCLUSION: Rates of intensification at a single
      clinic visit were quite low in all groups and were lowest in older patients with
      comorbidity.

PMID- 16108942
TI  - Mobility limitations in the Medicare population: prevalence and sociodemographic
      and clinical correlates.
AB  - OBJECTIVES: To examine the prevalence of and clinical markers associated with
      mobility limitations in Medicare Current Beneficiary Community Survey (MCBS)
      respondents. DESIGN: Cross-sectional analysis of a community survey. SETTING:
      Community. PARTICIPANTS: Twelve thousand seven hundred sixty-nine respondents
      from the 2001 MCBS, aged 65 and older. MEASUREMENTS: Four questions from the MCBS
      were used to create four levels of mobility limitation: none, mild, moderate, and
      severe. Sampling weights were used to calculate estimates of means and
      proportions of the entire Medicare population for each mobility limitation
      category. A polytomous logistic regression analysis was used to model the
      association between four levels of mobility limitation and sociodemographic and
      clinical variables. RESULTS: Prevalence of mobility limitations ranged from 9.5
      million (mild) to 1.2 million (severe). Increasing severity of mobility
      limitation was associated with older age, being female, reporting fair or poor
      health, being overweight, smoking, having a greater number of comorbidities,
      having an annual income below $25,000, having less than a high school education,
      being unmarried, and living with others. CONCLUSION: National prevalence
      estimates suggest that functional mobility limitation is a significant problem
      for many older adults and is associated with some potentially modifiable
      characteristics.

PMID- 16108943
TI  - Hypoalbuminemia 3 months after hospital discharge: significance for long-term
      survival.
AB  - OBJECTIVES: To determine change in albumin from hospital discharge to 3-month
      follow-up and the prognostic significance of persistent hypoalbuminemia in older
      veteran patients. DESIGN: A prospective cohort study. SETTING: A geriatric
      rehabilitation unit of a university-affiliated Department of Veterans Affairs
      hospital. PARTICIPANTS: The study population consisted of 282 subjects (of 322
      randomly selected discharges who were free of cancer and terminal conditions)
      that completed the 90-day postdischarge assessment; most were older (75.4+/-8.6),
      white (76%), and male (99%). MEASUREMENTS: Each subject completed a comprehensive
      discharge assessment, had a repeat albumin an average of 94 days later, and was
      then tracked for 5 years. The strongest predictors of survival were identified
      using Cox proportional hazards regression analysis. RESULTS: Between hospital
      discharge and the 3-month reassessment, albumins improved by more than 2 g/L in
      122 subjects (43%), stayed the same in 112 subjects (40%), and deteriorated by
      more than 2 g/L in the rest. During follow-up, 190 subjects (67%) died. Of the 38
      nutritional, functional, demographic, and illness severity variables evaluated,
      the 3-month postdischarge albumin was the strongest predictor of long-term
      mortality. Those with albumins less than 35 g/L had a 2.6 times greater mortality
      than those with albumins of 40 g/L or greater (relative risk=2.6, 95% confidence
      interval=1.8-3.8). After controlling for 3-month albumin, hospital-discharge
      albumin was not significantly associated with long-term mortality. CONCLUSION: In
      older people, a low serum albumin 3 months after hospital discharge is associated
      with a poor long-term prognosis. It is not known whether this represents ongoing
      inflammation or inadequate nutrition.

PMID- 16108944
TI  - Agreement between patient and proxy responses of health-related quality of life
      after hip fracture.
AB  - OBJECTIVES: To examine agreement between patient and proxy respondents on health
      related quality of life (HRQL) over time during the 6-month recovery after hip
      fracture. DESIGN: Prospective longitudinal cohort study. SETTING: A healthcare
      region serving Edmonton, Alberta, and the surrounding area. PARTICIPANTS: Two
      hundred forty-five patients aged 65 and older, were treated for hip fracture, and
      had Mini-Mental State Examination scores greater than 17; 245 family caregivers
      participated as proxy respondents. MEASUREMENTS: Primary outcome was HRQL (Health
      Utilities Mark 2 and Mark 3). Interviews were completed within 5 days after
      surgery and at 1, 3, and 6 months. Agreement was evaluated using intraclass
      correlation coefficients (ICCs). RESULTS: Agreement was considered moderate to
      excellent for HRQL. ICC values ranged from 0.50 to 0.85 (P<.001) for physically
      based observable dimensions of health status and from 0.32 to 0.66 (P<.01) for
      less-observable dimensions. Agreement improved with time. Time and the number of
      days between patient and proxy interviews were significant factors in accounting
      for patient-proxy differences. CONCLUSION: Although proxy and patient responses
      are not interchangeable, proxy responses provide an option for assessing function
      and health status in patients who are unable to respond on their own behalf.

PMID- 16108945
TI  - Association between acculturation and structural assimilation and mini-mental
      state examination-assessed cognitive impairment in older Mexican Americans:
      findings from the San Antonio Longitudinal Study of Aging.
AB  - Older Mexican Americans (MAs) have consistently scored lower on the Folstein Mini
      Mental State Examination (MMSE) than older European Americans (EAs). These lower
      scores may arise from factors other than those traditionally posited (age and
      education). Thus, this study examined the association between acculturation and
      structural assimilation and MMSE-assessed cognitive impairment, taking into
      account education, income, and other contextual factors. Subjects were
      participants in the San Antonio Longitudinal Study of Aging, a community-based
      study of chronic disease and functional status in 457 older MAs and 376 older
      EAs. Scales were used to measure two dimensions of acculturation: (family
      attitude, cultural values) and structural assimilation (functional integration
      into the broader American society). Logistic regression was used to examine the
      association between age, sex, acculturation, and structural assimilation and MMSE
      scores suggestive of cognitive impairment (<24). After adjusting for contextual
      factors (age, sex, education and household income), diseases (diabetes mellitus,
      stroke, and hypertension), and sensory impairments (hearing and vision),
      structural assimilation, but neither dimension of acculturation, was
      significantly and negatively associated with MMSE-assessed cognitive impairment.
      Older MAs in the lowest structural assimilation stratum were 1.89 times as likely
      to have MMSE-assessed cognitive impairment as those in the highest. Age,
      education, and visual impairment were also independently associated with
      cognitive impairment. These findings highlight the need for geriatricians to take
      contextual factors (including age, education, and structural assimilation) into
      account when interpreting MMSE scores of MA patients.

PMID- 16108946
TI  - Potential mediators of ethnic differences in physical activity in older Mexican
      Americans and European Americans: results from the San Antonio Longitudinal Study
      of Aging.
AB  - Factors were examined that might explain reported ethnic differences in leisure
      time physical activity (LTPA) between Mexican Americans (MAs) and European
      Americans (EAs). Data were from a random sample of 749 community-dwelling MAs and
      EAs, aged 65 and older, who participated in the San Antonio Longitudinal Study of
      Aging (SALSA) baseline examination. Variables examined included LTPA measured as
      kilocalories of energy expended per week, contextual variables (age, sex,
      socioeconomic status (SES), acculturation/structural assimilation), psychosocial
      measures (self-esteem, mastery, perceived health control), lifestyle variables
      (fat avoidance, current alcohol drinker, years smoking, body mass index (BMI)),
      and presence of chronic diseases (diabetes mellitus, angina pectoris, myocardial
      infarction, stroke, hypertension, arthritis, chronic obstructive pulmonary
      disease, depression, mild cognitive impairment). Hierarchical multiple regression
      was used to examine potential mediators of the ethnic group-LTPA association. EAs
      expended almost 300 kcal/wk more energy than did MAs (1,287 kcal/wk vs 1,001
      kcal/wk). SES and psychosocial (self-esteem), lifestyle (fat avoidance, smoking,
      BMI), and disease (depression) factors that vary by SES explained this ethnic
      difference. In MAs, structural assimilation, but not acculturation, was
      significantly associated with LTPA independent of SES. Self-esteem, BMI, and
      depression explained this association. Psychosocial resources, lifestyle
      behaviors, and depression explain differences in LTPA between older MAs and EAs.
      Interventions to increase LTPA in both ethnic groups should be targeted
      especially at women and persons who have low self-esteem, smoke, and are obese or
      depressed. In MAs, additional emphasis should be focused on those who are less
      structurally assimilated into the broader American society.

PMID- 16108947
TI  - Historical perspective on pressure ulcers: the decubitus ominosus of Jean-Martin
      Charcot.
AB  - Jean-Martin Charcot was a towering figure in the French medical community in the
      19th century. Among the diseases he studied was the decubitus, or pressure ulcer,
      as it is commonly called today. He did not believe that pressure or local
      irritation were causative factors for the decubitus but rather subscribed to the
      "neurotrophic theory," which held that damage to the central nervous system led
      directly to its occurrence. Charcot observed that many patients who developed
      eschar of the sacrum and buttocks died soon afterwards, and referred to this
      lesion as the decubitus ominosus, implying that its occurrence heralded impending
      death. His description of the evolving decubitus is extraordinarily detailed and
      accurate and includes complications that are seldom seen today, such as
      gangrenous metastases to the lung and invasion of the spinal cord. Charcot's
      therapeutic nihilism is largely a product of the limited medical technology of
      his day. The importance of risk factor assessment and timely intervention for
      persons at risk is now understood. In addition, it is recognized that not all
      pressure ulcers are unavoidable and that many ulcers, particularly those in early
      stages, can be reversed. Comparing Charcot's view of the decubitus with our own,
      insight is provided into the way medicine is practiced today.

PMID- 16108949
TI  - Improving urinary incontinence in nursing home residents: are we FIT to be tied?

PMID- 16108950
TI  - The tangled story of plaques and arteries.

PMID- 16108951
TI  - Abdominal and flank pain as an unusual presentation of pulmonary embolism: a case
      report.

PMID- 16108952
TI  - Cataract and cognitive function in older adults.

PMID- 16108953
TI  - The effect of risperidone on nursing burden associated with caring for patients
      with dementia.

PMID- 16108955
TI  - Two fundamental problems in geriatric medicine.

PMID- 16108957
TI  - Acquired color blindness in an elderly male patient from recurrent metastatic
      prostate cancer.

PMID- 16108959
TI  - Encephalopathy secondary to a portosystemic venous shunt in a nonagenarian.

PMID- 16108960
TI  - Potential bias in "controls" used in a heart failure disease-management program.

PMID- 16108962
TI  - Obesity in elderly hospitalized patients: Gruppo Italiano di Farmacovigilanza
      nell'Anziano.

PMID- 16108961
TI  - Treatment persistency with rivastigmine and donepezil in a large state medicaid
      program.

PMID- 16108963
TI  - Prevention of chronic kidney and vascular disease: toward global health equity-
      the Bellagio 2004 Declaration.
AB  - Chronic kidney disease (CKD) not only reflects target organ injury in systemic
      vascular disease in the general population and in association with diabetes,
      hypertension, and smoking, but it is recognized as one of the major risk factors
      in the pathogenesis and outcome of cardiovascular disease. Recent surveys have
      revealed that the prevalence of CKD, particularly the hidden mild form (mildly
      elevated levels of serum creatinine or urinary albumin excretion), is
      surprisingly high in the general population. In recent years, the global epidemic
      of type 2 diabetes has led to an alarming increase in the number of patients with
      CKD. Most patients with CKD (over 50 million individuals worldwide) succumb to
      cardiovascular events, while each year over 1 million develop end-stage renal
      failure, which requires costly treatment and in many countries of the world,
      unaffordable renal replacement therapy by chronic dialysis or renal
      transplantation. Alarmed by the immense challenge to human morbidity and the
      economic burden of CKD and ensuing systemic cardiovascular disease, the
      International Society of Nephrology convened a multidisciplinary group of expert
      physicians and public health leaders from around the world to develop strategies
      to delay and avert this bleak future by effective prevention of CKD based on
      awareness, early detection, and effective treatment.

PMID- 16108964
TI  - Prevention of chronic kidney disease: a global challenge.
AB  - In view of the increasing number of patients requiring renal replacement therapy
      (RRT) every year worldwide, attention has focused over the last two decades on
      meeting the health care need of patients with end-stage renal failure (ESRF).
      More recently, increasing awareness of the growing burden of chronic kidney
      disease (CKD), with a large percentage of the population affected by early stages
      of CKD, has shifted attention and health care priority to the prevention and
      early detection of CKD. This article addresses issues related to general
      population as well as targeted screening, favoring the latter. It also examines
      some of the screening initiatives undertaken in both the developing and developed
      worlds. It also highlights the links between albuminuria, CKD, and cardiovascular
      disease (CVD) as an increasing number of studies identify
      albuminuria/proteinuria, as well as CKD as major markers of CVD. Finally, a brief
      review is included of primary and secondary intervention strategies for CKD and
      issues related to their implementation: manpower and funding.

PMID- 16108965
TI  - Cardiovascular risk in diabetic kidney disease: a model of chronic renal disease.

PMID- 16108966
TI  - Prevention of progression and remission/regression strategies for chronic renal
      diseases: can we do better now than five years ago?
AB  - The prevalence of chronic renal diseases is increasing worldwide. There is a
      great need to identify therapies that arrest disease progression to end-stage
      renal failure. Inhibition of renin-angiotensin system both by ACE inhibitors and
      angiotensin II receptor antagonists is probably the best therapeutic option
      available. Several large, multicenter studies have indeed shown a significant
      reduction in the risk of doubling baseline serum creatinine or progression toward
      end-stage renal failure in diabetic and nondiabetic patients with chronic
      nephropathies treated with ACE inhibitors or angiotensin II receptor antagonists.
      However, the number of patients that reach end-stage renal failure is still
      considerably high. Significant reduction of the incidence of end-stage renal
      disease is likely to be achieved in the next future for chronic nephropathies,
      provided that we can improve the degree of renoprotection. This goal may be
      attainable with a more complex strategy than with a single or dual pharmacologic
      intervention on the renin-angiotensin system. Strict control of blood pressure
      and protein excretion rate, lowering of blood lipids, tight glucose control for
      diabetics, and lifestyle changes form part of the future multimodal protocol for
      management of patients with chronic nephropathies.

PMID- 16108967
TI  - The kidney, a cardiovascular risk marker, and a new target for therapy.
AB  - Both reduced filtration power and increased excretion of albumin in the urine are
      powerful markers for renal and cardiovascular progressive function loss. These
      risk markers indicate the risk above and beyond the conventional existing risk
      markers/factors. The risk is substantial, because both reduced filtration and
      microalbuminuria are highly prevalent in the general population, matching in
      prevalence with the most well-known risk factor, hypertension. Therapeutic
      interventions to preserve renal and cardiovascular function, such as with
      angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists,
      are highly effective, particularly in those patients that have reduced filtration
      power. In addition, short-term reduction of albuminuria that follows the renin
      angiotensin-aldosterone-system intervention appears to be predictive of long-term
      cardiovascular and renal protection. In conclusion, estimated glomerular
      filtration rate as well as albumin excretion in the urine are powerful predictors
      for cardiovascular and renal outcome and should be used as such. Intervention and
      prevention could be aimed at not only at reducing conventional risk markers, but
      also at reducing albuminuria.

PMID- 16108968
TI  - End-stage renal disease prevention strategies in Latin America.
AB  - Latin America (LA), defined here as the countries in the Western hemisphere
      located south of the United States, is a region with a total population of nearly
      520,000,000 that increases 1.5% annually and has a human development index of
      0.77. The countries that form this region present extreme contrasts. These
      contrasts are first and foremost within the countries themselves, because
      extremes of wealth and poverty are present in their social and economic fabric.
      In addition, in LA a vast variety of government modalities and political systems
      are represented. Therefore, in order for prevention strategies to be effective,
      they need to be tailored to the specific characteristics and idiosyncrasies of
      individual nations. This article will address the following aspects: first, a
      broad outline of the basic health statistics in LA, with focus on treatment of
      end-stage renal disease and its derived economic burden. Data from LA countries
      will be contrasted with 95% confidence interval of corresponding data from 10
      industrialized countries (Canada, France, Germany, Italy, Japan, United Kingdom,
      United States, Spain, Sweden, and Switzerland). Second, we will discuss the
      prevalence of some risk factors for end-stage renal disease in the nations of the
      region. For this reason, we will focus on data that provide reliable information.
      Finally, we will consider general guidelines for the implementation of prevention
      strategies that may have common applicability in LA countries.

PMID- 16108969
TI  - Preventive strategies of renal failure in the Arab world.
AB  - The prevalence of both acute and chronic renal failure is high in the Arab world.
      Data available on the exact prevalence of various renal diseases are very
      limited. Nevertheless, the reported prevalence of chronic renal failure is 80 to
      120 per million population (pmp) in the Kingdom of Saudi Arabia and 225 pmp in
      Egypt. This is in comparison with the reported prevalence of 283 pmp in Europe,
      975 pmp in the United States, and 1149 pmp in Japan. Lower prevalence rates
      reported in this region could be due to underreporting. The economic burden of
      renal replacement on health care providers is enormous. In the Kingdom of Saudi
      Arabia, the estimated cost per annum incurred toward maintenance hemodialysis is
      US 19,400 US dollars and, considering that there are more than 7200 patients on
      regular dialysis in this country, the total expenditure is enormous. Such large
      amounts may be beyond the monetary capacity of many countries in this region
      because of limited financial resources. These figures clearly suggest that there
      is an urgent need to establish a massive prevention program. The strategy adapted
      should be innovative and imaginative and should be one that is maximally cost
      effective. Paradoxically, in the Arab world, we have a good opportunity to reduce
      the incidence of kidney failure (chronic and acute) substantially by
      appropriately chosen models. This is because many of the causes of renal failure
      are eminently preventable. In fact, a rough estimate is that these programs, if
      successful, can reduce the incidence by as much as 40% (personal communication,
      Shaheen, 2003). It is worthy of mention that, in the Arab world, the budget for
      research is about 0.15% of the national domestic product compared with the
      international average of 1.5%. In this article, we concentrate on some of the
      main causes of renal failure in the Arab world that we feel can be prevented and
      suggest ways that can best address this issue.

PMID- 16108970
TI  - Chronic kidney disease and its prevention in India.
AB  - Chronic kidney disease (CKD) is an important, chronic, noncommunicable disease
      epidemic that affects the world, including India. Because of the absence of a
      renal registry in India, the true magnitude of CKD/end-stage renal disease (ESRD)
      is unknown. Two community-based studies, although methodologically different,
      have shown a prevalence of chronic renal failure of 0.16% and 0.79%. The cost of
      maintenance hemodialysis for a single session varies between 10 US dollars to 40
      between government-run and private hospitals. The average cost of erythropoetin
      is approximately 150 US dollars to 200 per month. The cost of chronic ambulatory
      peritoneal dialysis with "Y" set at 3 exchanges per week, which most patients in
      India do, is US 400 US dollars per month. The cost of a renal transplant (RT)
      procedure is approximately US 700 US dollars to 800 in the government sector and
      6000 US dollars in the private sector. The cost of immunosuppression with basic
      triple immunosuppression drugs (cyclosporine, steroid, and azathioprin) is US 250
      US dollars per month. There are hardly any state-funded medical treatment and
      medical insurance facilities for CKD and ESRD patients in India. India has nearly
      700 nephrologists and approximately 400 dialysis units with 1000 dialysis
      stations, with the majority being in the private sector. A maximum of 2% of
      patients can be subjected to maintenance hemodialysis. Until now, approximately
      3000 patients have been initiated on chronic ambulatory peritoneal dialysis.
      India has approximately 100 RT centers, mostly in private setup, and not more
      than 3000 to 4000 RTs are performed annually. Thus, only 3% to 5% of all patients
      with ESRD in India get some form of renal replacement therapy. Thus, planning for
      prevention of CKD on a long-term basis is the only practical solution for India.
      It appears that even in India, diabetes and hypertension are responsible for 40%
      to 50% of all cases of chronic renal failure. Screening for these 2 diseases and
      CKD is simple and easy to perform. The best approach will be to start screening
      for CKD in a high-risk group, like first-degree relatives of patients with
      diabetes, hypertension, and CKD, and simultaneously making a platform to run the
      program through the existing health care system of the country. The key issue of
      funding the program needs to be explored. Initial funding may come from
      international agencies like the World Health Organization, World Bank, and
      International Society of Nephrology, along with support from the country itself.
      Ultimately, funding has to be sustained from our own existing health care system.

PMID- 16108971
TI  - Opportunities for a chronic disease outreach program in China.
AB  - The comparison of the prevalence of patients on regular dialysis treatment (RDT)
      in the 3 areas of Greater China (Taiwan, Hong Kong, and Mainland) with that of
      the United States and Japan shows that, unlike Taiwan, in which RDT has a higher
      prevalence than in the United States and Japan, in Mainland China such prevalence
      is enormously lower. To make the situation more in line with that of Taiwan,
      around 2 million patients would need to be treated in Mainland China, which would
      be a tremendous financial burden. Prevention is the only way to improve the
      situation. Preliminary information regarding an epidemiologic study on the
      population of Zhuhai, a town in Southeast China, planned in collaboration with
      the Commission for the Global Advancement of Nephrology of the International
      Society of Nephrology and the 5th Affiliated Hospital of the Sun-Yat-Sen
      University in Zhuhai, is given here.

PMID- 16108972
TI  - Public health in Africa: what is new--the context, the gains, the losses, the
      renewed public health, and the way forward.

PMID- 16108973
TI  - International aid and medical practice in the less-developed world: doing it
      right, what can renal organizations learn?
AB  - The delivery of health care in poorer countries is reliant on international aid
      organizations. This article will focus on international aid and medical practice
      in the developing world. It will review the general issues, practices, and
      problems with international aid in the medical arena and will then focus on
      international aid, kidney detection, and prevention programs. The article will
      analyze some of the existing and successful organizations and their initiatives.
      The first part of this article will analyze such aspects as: the access of
      existing resources and available aid projects; the establishment of contact with
      international aid projects; the access of funds for the development of the
      project and, once it is established, the management of those funds; the planning
      of projects; and the role of research in international aid and medical practice
      both as a means of accessing resources and of managing the project. The second
      part of the article will look more specifically at issues in nephrology and
      international aid. The focus will be on current programs in nephrology and the
      critical appraisal of some existing programs. The last part will focus
      specifically on practical tasks which are needed when accessing international aid
      for medical projects. It will draw on the experiences of various programs and
      then outline suggested phases one should consider when establishing aid projects
      in order to best implement them. Kidney groups with intentions to deliver
      prevention and management strategies to developing countries need to learn from
      the experiences of existing international aid organizations and chronic kidney
      disease programs.

PMID- 16108974
TI  - Strategies for national health care systems and centers in the emerging world:
      Central America and the Caribbean--the case of Cuba.
AB  - Over 40% of the 76 million people in Central America and the Caribbean live in
      poverty with no safety net. Communicable and noncommunicable diseases
      significantly impact morbidity and mortality, and a tendency toward aging
      suggests increasing prevalence of chronic conditions. Among factors related to
      renal diseases: obesity is an epidemic among the near-poor; prevalence of
      diabetes mellitus is 6% to 8%; and hypertension is 8% to 30%. The region's racial
      ethnic composition--associated with depressed socioeconomic conditions--is
      comparable to US minorities showing greater chronic renal disease (CRD) rates
      than those registered in Central America and the Caribbean, which suggests that
      this region may be among the world's most seriously affected by CRD. This is a
      reality masked by lack of health care coverage. Health policies generally have
      not prioritized human resource development, and training is biased toward
      curative care instead of prevention. Nephrologists are less than 20 per million
      population in most countries. Health care infrastructures are poor, lacking the
      primary care facilities charged with prevention. Cuba shares economic limitations
      with its neighbors but is one of the region's least socially stratified
      countries, with a universal, free, and public health care system emphasizing
      primary health care and prevention. Human resource development has resulted in
      59.6 physicians per 10,000 inhabitants and a family physician program covering
      the whole population. A national renal diseases program incorporates preventive
      strategies at all care levels. Nevertheless, early detection of patients with CRD
      remains a challenge in the Cuban context. In Central America and the Caribbean,
      prevention is the key to reducing medical, social, and economic costs of renal
      disease.

PMID- 16108975
TI  - Early detection and prevention of diabetic nephropathy: a challenge calling for
      mandatory action for Mexico and the developing world.
AB  - During the last decades, developing countries have experienced an epidemiologic
      transition characterized by a reduction of infectious diseases and an increase of
      chronic degenerative diseases. This situation is generating tormenting public
      health, financial, and social consequences. Of particular relevance is type 2
      diabetes mellitus and its chronic complications, particularly cardiovascular
      disease and diabetic nephropathy, because mortality of the patient with diabetes
      is, in most instances, related to these complications. There is a clear need to
      implement diagnostic and treatment strategies to reduce risk factors for
      development of diabetes (primary prevention), to detect risk factors of chronic
      complications in early stages of diabetes (secondary prevention), and to prevent
      further progression of those that already have renal injury (tertiary
      prevention). Microalbuminuria is an early marker of renal injury in diabetes, and
      its early detection can help the timely use of renal preventive measures, which
      would avoid the extremely high costs of renal replacement treatment for end-stage
      renal disease as well as that of other cardiovascular complications. Preventive
      strategies are of very little or no impact, if the primary physician has limited
      knowledge about the natural history of diabetic nephropathy, the beneficial
      effect of early preventive maneuvers for delaying its progression, and the social
      and economic impact of end-stage renal disease. It is therefore imperative to
      assure in our health systems that general practitioners have the ability and
      commitment to detect early diabetes complications, in order to promote actions
      that support regression or retard highly morbid cardiovascular and renal
      conditions.

PMID- 16108976
TI  - Chronic renal diseases as a public health problem: epidemiology, social, and
      economic implications.
AB  - The impact of chronic kidney disease (CKD) on the global burden of diseases is
      probably underestimated by current methods of evaluation. However, CKD are
      emerging as a major health problem. First, the costs of renal replacement therapy
      are excedingly high and are consuming a significant proportion of health care
      budgets of developed countries, while in developing countries are out of reach.
      Second, complex interaction are clearly emerging between chronic kidney,
      cardiovascular disease, and diabetes.

PMID- 16108977
TI  - A chronic disease outreach program for Aboriginal communities.
AB  - BACKGROUND: Our objective is to describe a program to improve awareness and
      management of hypertension, renal disease, and diabetes in 3 remote Australian
      Aboriginal communities. METHODS: The program espouses that regular integrated
      checks for chronic disease and their risk factors are essential elements of
      regular adult health care. Programs should be run by local health workers,
      following algorithms for testing and treatment, with backup, usually from a
      distance, from nurse coordinators. Constant evaluation is essential to develop
      community health profiles and adapt program structure. RESULTS: Participation
      ranged from 65% to 100% of adults. Forty-one percent of women and 72% of men were
      current smokers. Body weight varied markedly by community. Although excessive in
      all, rates of chronic diseases also differed markedly among communities. Rates
      increased with age, but the greatest numbers of people with morbidities were
      middle age and young adults. Multiple morbidities were common by middle age.
      Hypertension and renal disease were early features, whereas diabetes was a
      variable and later manifestation of this integrated chronic disease syndrome.
      Adherence to testing and treatment protocols improved markedly over time.
      Substantial numbers of new diagnoses were made. Blood pressure improved in people
      in whom antihypertensive agents were started or increased. Components of a
      systematic activity plan became more clearly defined with time. Treatment of
      people in the community with the greatest disease burden posed a large additional
      workload. Lack of health workers and absenteeism were major impediments to
      productivity. CONCLUSION: We cannot generalize about body habitus, and chronic
      disease rates among Aboriginal adults. Pilot data are needed to plan resources
      based on the chronic disease burden in each community. Systematic screening is
      useful in identifying high-risk individuals, most at an early treatable stage.
      Community-based health profiles provide critical information for the development
      of rational health policy and needs-based health services.

PMID- 16108978
TI  - The changing patterns of chronic kidney disease: the need to develop strategies
      for prevention relevant to different regions and countries.
AB  - Chronic diseases are now in pandemic proportions and are the major cause of
      morbidity and mortality worldwide. Long-term predictions show that the burden
      will fall increasingly on developing countries. Type II diabetes is now the major
      global cause of chronic kidney disease. However, chronic kidney disease should
      not be viewed in isolation, because it is also a major risk factor for
      cardiovascular deaths. It is both a medical and economic imperative to introduce
      screening and management programs for chronic kidney disease, diabetes,
      hypertension, and cardiovascular disease worldwide but particularly in the
      emerging world. Such programs should be tailored to the needs of the individual
      country, involve local health providers, be assessable as to their efficacy, and
      become self-sufficient within 5 years.

PMID- 16108979
TI  - Integrated approaches to prevention and control of chronic conditions.
AB  - Integrated approaches to prevention and control of chronic conditions. Chronic
      conditions currently account for more than 50% of the global disease burden, and
      this figure is projected to continue to rise. Yet, around the world, health care
      systems are not organized to provide effective and efficient care for chronic
      health problems. Health care systems have evolved around the concept of acute,
      infectious disease, and they perform best when addressing patients' acute and
      urgent symptoms. Without change, health care systems will grow increasingly
      inefficient and ineffective. Effective prevention, management, and rehabilitation
      of chronic conditions require an evolution of health care, away from a model that
      is focused on acute symptoms toward a coordinated, comprehensive system of care.
      The results of this shift include less waste and improved efficiency. Integrated
      health care models that transcend specific illnesses provide a feasible solution.
      The World Health Organization's Innovative Care for Chronic Conditions Framework
      provides a flexible but comprehensive model to build or redesign health systems
      in accord with local resources and demands.

PMID- 16108980
TI  - Electronic strategies for information and research: cyberNephrology/cyberMedicine
      in the emerging world.
AB  - Communication and medicine have evolved together. Internet resources now provide
      an unprecedented opportunity to provide health assistance to the developing
      world. The International Society of Nephrology Informatics Commission and
      National Kidney Foundation cyberNephrology initiative
      (http://www.cybernephrology.org) have created e-mail discussion groups (e.g.,
      NEPHROL, NEPHKIDS, and so forth) and online texts and web resources (e.g., the
      Schrier Atlas: http://www.kidneyatlas.org) that are, in many respects, ahead of
      other areas of medicine. On the other hand, nephrology is quite behind in its
      embrace of some specific communications initiatives that could benefit emerging
      nations: the Health InterNetwork Access to Research Initiative program, which
      provides free full-text access to medical journals and books in poorer countries;
      the Global Health Network Supercourse, which provides specially designed online
      lectures for the developing world; and Internet2/Abilene and similar research
      networks around the world, which provide reliable, guaranteed bandwidth for high
      quality Internet videoconferencing as an alternative to face-to-face lectures and
      meetings. The intent of many educational ventures in nephrology, particularly in
      the clinical practice guideline realm (National Kidney Foundation Kidney Disease
      Outcomes Quality Initiative, Kidney Disease Improving Global Outcomes, and so
      forth), is not just to disseminate information but to change human behavior:
      physician practice and referral patterns, patient compliance, and so forth.
      Concepts from the worlds of marketing and entertainment, where the science of
      changing human behavior is highly evolved, can be used to create high-impact,
      educational offerings to promote health. They can also be highly beneficial to
      share Internet educational innovations and future vision across boundaries of
      medical specialties, which is part of the intent of the cyberMedicine joint
      venture (http://www.cyber-medicine.org).

PMID- 16108981
TI  - Extending the evaluation of a computer system used as a microswitch for word
      utterances of persons with multiple disabilities.
AB  - BACKGROUND: Micro-switches can be vital tools to help individuals with extensive
      multiple disabilities acquire control of environmental stimulation. This study
      was aimed at extending the evaluation of a computer system used as a microswitch
      for word utterances with three participants with multiple disabilities. METHOD:
      Sets of 7 or 12 word utterances were used for the participants. The utterances
      were divided into three groups, which were exposed to intervention successively.
      During the intervention and a 2-month post-intervention check, the participants'
      emission of the target utterances led the system to present favourite, matching
      stimuli (i.e. provided that it recognized the utterances). RESULTS: Intervention
      data showed that (1) the participants increased the frequencies of the target
      utterances and (2) the computer system recognized approximately 80% of those
      utterances. These findings were maintained at the post-intervention check. An
      analysis of the levels of occurrence of individual utterances showed
      statistically significant differences among them, in line with the notions of
      preference and choice. CONCLUSIONS: The computer system was useful as a
      microswitch to enable access to favourite stimuli. There is a need to improve the
      accuracy of the system with respect to its recognition of the participants'
      utterances.

PMID- 16108982
TI  - Blink rate in boys with fragile X syndrome: preliminary evidence for altered
      dopamine function.
AB  - BACKGROUND: Dopamine, a neurotransmitter involved in motor and cognitive
      functioning, can be non-invasively measured via observation of spontaneous blink
      rates. Blink rates have been studied in a number of clinical conditions including
      schizophrenia, autism, Parkinsons, and attention deficit/hyperactivity disorder
      with results implicating either hyper or hypo dopaminergic states. METHODS: This
      study examined spontaneous blink rate in boys with fragile X syndrome (FXS).
      Blink rates of boys (4-8 years old) with FXS (n = 6) were compared with those of
      age-matched typically developing boys (n = 6) during active and passive tasks.
      Blink rates (blinks per minute) for each task were compared between the two
      groups. Then, the relation between blink measures and core FXS-related features
      [problem behaviours, arousal, fmr 1 protein (FMRP)] were examined within the
      group of boys with FXS. RESULTS: Blink rate in boys with FXS was significantly
      higher than typically developing boys during passive tasks. Within the FXS group,
      there were significant correlations between blink rate and problem behaviours and
      physiological arousal (i.e. heart activity) but not with FMRP. CONCLUSIONS:
      Observed differences in spontaneous blink rate between boys with and without FXS
      and the relation between blink rate and physiological and behavioural measures in
      boys with FXS suggests that further work examining dopamine dysfunction as a
      factor in the pathophysiology of FXS may be warranted.

PMID- 16108983
TI  - Preschool children with intellectual disability: syndrome specificity, behaviour
      problems, and maternal well-being.
AB  - BACKGROUND: Children with intellectual disability (ID) are at heightened risk for
      behaviour problems and diagnosed mental disorder. Likewise, mothers of children
      with ID are more stressed than mothers of typically developing children. Research
      on behavioural phenotypes suggests that different syndromes of ID may be
      associated with distinct child behavioural risks and maternal well-being risks.
      In the present study, maternal reports of child behaviour problems and maternal
      well-being were examined for syndrome-specific differences. METHODS: The present
      authors studied the early manifestation and continuity of syndrome-specific
      behaviour problems in 215 preschool children belonging to 5 groups (typically
      developing, undifferentiated developmental delays, Down syndrome, autism,
      cerebral palsy) as well as the relation of syndrome group to maternal well-being.
      RESULTS: At age 3, children with autism and cerebral palsy showed the highest
      levels of behaviour problems, and children with Down syndrome and typically
      developing children showed the lowest levels. Mothers of children with autism
      reported more parenting stress than all other groups. These syndrome-specific
      patterns of behaviour and maternal stress were stable across ages 3, 4 and 5
      years, except for relative increases in behaviour problems and maternal stress in
      the Down syndrome and cerebral palsy groups. Child syndrome contributed to
      maternal stress even after accounting for differences in behaviour problems and
      cognitive level. CONCLUSIONS: These results, although based on small syndrome
      groups, suggest that phenotypic expressions of behaviour problems are manifested
      as early as age 3. These behavioural differences were paralleled by differences
      in maternal stress, such that mothers of children with autism are at elevated
      risk for high stress. In addition, there appear to be other unexamined
      characteristics of these syndromes, beyond behaviour problems, which also
      contribute to maternal stress.

PMID- 16108984
TI  - Adaptive functioning and behaviour problems in relation to level of education in
      children and adolescents with intellectual disability.
AB  - BACKGROUND: The interrelationship between adaptive functioning, behaviour
      problems and level of special education was studied in 186 children with IQs
      ranging from 61 to 70. The objective was to increase the insight into the
      contribution of adaptive functioning and general and autistic behaviour problems
      to the level of education in children with intellectual disability (ID). METHODS:
      Children from two levels of special education in the Netherlands were compared
      with respect to adaptive functioning [Vineland Adaptive Behavior Scales (VABS)],
      general behaviour problems [Child Behavior Checklist (CBCL)] and autistic
      behaviour problems [Autism Behavior Checklist (ABC)]. The effect of behaviour
      problems on adaptive functioning, and the causal relationships between behaviour
      problems, adaptive functioning and level of education were investigated. RESULTS:
      Children in schools for mild learning problems had higher VABS scores, and lower
      CBCL and ABC scores. The ABC had a significant effect on the total age equivalent
      of the VABS in schools for severe learning problems, the CBCL in schools for mild
      learning problems. A direct effect of the ABC and CBCL total scores on the VABS
      age equivalent was found, together with a direct effect of the VABS age
      equivalent on level of education and therefore an indirect effect of ABC and CBCL
      on level of education. CONCLUSIONS: In the children with the highest level of
      mild ID, adaptive functioning seems to be the most important factor that directly
      influences the level of education that a child attends. Autistic and general
      behaviour problems directly influence the level of adaptive functioning.
      Especially, autistic problems seem to have such a restrictive effect on the level
      of adaptive functioning that children do not reach the level of education that
      would be expected based on IQ. Clinical implications are discussed.

PMID- 16108985
TI  - Effects of integrated or segregated sport participation on the physical self for
      adolescents with intellectual disabilities.
AB  - BACKGROUND: The purpose was to examine the effects of the type of athletic
      programme (integrated vs. segregated) on the athletic domain of perceived
      competence and on general self-worth. METHODS: Participants were 32 adolescent
      females with intellectual disabilities (ID), divided equally into four groups:
      (1) segregated swimming; (2) integrated swimming; (3) adapted physical activity;
      and (4) sedentary. The experimental treatment was 32 months long; for sport
      groups, this involved 2 h of training each week and 12 competitive meets. The
      Harter Self-Perception Profile for Children 11 times was administrated to
      determine changes in perceived physical competence and general self-worth.
      RESULTS: Results indicated (1) no change in perceived general self-worth for the
      four groups; (2) significantly lower perceived athletic competence only for the
      integrated swimming group, despite the increase in athletic performance.
      CONCLUSIONS: The integrated sport participation for adolescents with ID placed in
      segregated school is useful but needs to be well controlled by professional in
      physical education.

PMID- 16108986
TI  - Response to Verri et al. ( Journal of Intellectual Disability Research 48, 679
      686): is there room for hope when considering the problem of late diagnosis in
      intellectual disability?

PMID- 16108988
TI  - Container contamination as a possible source of a diarrhoea outbreak in Abou
      Shouk camp, Darfur province, Sudan.
AB  - Diarrhoea is one of the five major causes of death in an emergency setting and
      one of the three main causes of death in children (Curtis and Cairncross, 2003).
      In June 2004, an outbreak of shigellosis was confirmed in Abou Shouk camp in the
      Northern Darfur province of Sudan. As water testing showed no contamination, it
      was assumed that post-collection contamination was happening. The decision was
      taken to launch a programme of mass disinfection of all water containers in order
      to break the contamination cycle. Diarrhoea figures from the clinics showed a
      fall in cases following the cleaning campaign. It is extremely difficult to
      obtain good and statistically rigorous data in an emergency setting, the priority
      being to intervene rapidly to prevent further cases of diarrhoea. However, the
      results do appear to indicate that the disinfection programme has had an impact
      on the prevalence of bloody and watery diarrhoea.

PMID- 16108989
TI  - Restoring sanitation services after an earthquake: field experience in Bam, Iran.
AB  - A powerful earthquake hit the city of Bam in southeast Iran on 26 December 2003.
      In its aftermath, a number of international relief agencies, including Oxfam,
      assisted in providing emergency sanitation services. Oxfam's programme consisted
      of constructing and repairing toilets and showers in villages located outside of
      the city. In contrast with other organisations, Oxfam opted for brick-work
      structures, using local materials and human resources rather than prefabricated
      cubicles. The choice illustrates the dilemmas faced by agencies involved in
      emergency sanitation: responding to needs in a manner consistent with
      international standards and offering assistance in a timely fashion while
      involving beneficiaries. Following a preliminary survey, Oxfam concluded that the
      provision of showers and latrines, in addition to utilisation of local materials
      and human resources, was essential for ensuring well-being, empowerment and
      dignity among members of the affected population, thereby maximising the
      benefits.

PMID- 16108990
TI  - Standardising and mapping open-source information for crisis regions: the case of
      post-conflict Iraq.
AB  - Painting an accurate picture of the situation on the ground in countries in
      crisis is vital for the efficiency of humanitarian aid and reconstruction
      agencies. This study describes a method for standardising and mapping the
      plethora of open-source information. The test site for the study is post-conflict
      Iraq. Important information on aid distribution, reconstruction and security in
      Iraq can be derived from the reports of humanitarian aid agencies and the media,
      before being formatted, inserted into a database and mapped. The product is a
      visual, cartographic structure of otherwise random information, showing which
      organisations are working in the country, which thematic and geographic areas are
      being prioritized in the field, and which areas most frequently experience
      security events. This type of mapping not only highlights the overall working
      environment within different parts of the country, but it may also serve as a
      decision-making tool for donors and humanitarian aid agencies planning to deploy
      personnel.

PMID- 16108991
TI  - A cluster-based decision support system for estimating earthquake damage and
      casualties.
AB  - This paper describes a Decision Support System for Disaster Management (DSS-DM)
      to aid operational and strategic planning and policy-making for disaster
      mitigation and preparedness in a less-developed infrastructural context. Such
      contexts require a more flexible and robust system for fast prediction of damage
      and losses. The proposed system is specifically designed for earthquake
      scenarios, estimating the extent of human losses and injuries, as well as the
      need for temporary shelters. The DSS-DM uses a scenario approach to calculate the
      aforementioned parameters at the district and sub-district level at different
      earthquake intensities. The following system modules have been created: clusters
      (buildings) with respect to use; buildings with respect to construction typology;
      and estimations of damage to clusters, human losses and injuries, and the need
      for shelters. The paper not only examines the components of the DSS-DM, but also
      looks at its application in Besiktas municipality in the city of Istanbul,
      Turkey.

PMID- 16108992
TI  - Comparing reactions to two severe tornadoes in one Oklahoma community.
AB  - The authors compared the effect of the 3 May 1999 F5 and 8 May 2003 F3 tornadoes
      on the community of Moore, Oklahoma, by canvassing damaged areas after both
      tornadoes and surveying residents. Significantly more 1999 than 2003 residents
      reported property damage and injuries. Television and tornado sirens were the
      most common warnings each year, however, more 1999 residents received and
      responded to television warnings. Importantly, storm shelters were used more
      frequently in 2003. Fifty-one per cent of residents who experienced both
      tornadoes took the same amount of protective action in 2003 as they had in 1999;
      22% took less; and 27% took more. Residents who took less action said that the
      reason for doing so was inadequate warning and shelter. First-hand experience of
      tornadoes prompts people to heed warnings when adequate notification is received
      and to take effective protective action when adequate shelter is available.

PMID- 16108995
TI  - Annotation: Economic evaluations of child and adolescent mental health
      interventions: a systematic review.
AB  - BACKGROUND: Recognition has grown over recent years of the need for economic
      information on the impacts of child and adolescent mental health problems and the
      cost-effectiveness of interventions. METHODS: A range of electronic databases
      were examined using a predefined search strategy to identify economic studies
      which focused on services, pharmacological interventions and other treatments for
      children and adolescents with a diagnosed mental health problem or identified as
      at risk of mental illness. Published studies were included in the review if they
      assessed both costs and outcomes, with cost-effectiveness being the primary
      interest. Studies meeting the criteria for inclusion were assessed for quality.
      RESULTS: There are still relatively few economic evaluations in this field.
      Behavioural disorders have been given relatively greater attention in economic
      evaluations of child and adolescent mental health. These studies tentatively
      suggest child behavioural gains and parent satisfaction from parent and child
      training programmes, although the cost-effectiveness of the location of delivery
      for behavioural therapies is less clear. In general, the quality of economic
      evaluations was limited by small sample sizes, constrained measurement of costs,
      narrow perspectives and over-simple statistical and econometric methods.
      CONCLUSION: Economic evaluations in the field of child and adolescent mental
      health interventions are few in number and generally poor in quality, although
      the number of studies being undertaken now appears to be rising.

PMID- 16108996
TI  - Developmental trajectories of conduct problems and hyperactivity from ages 2 to
      10.
AB  - BACKGROUND: Conduct problems (CP) and hyperactivity/attention problems (HAP) are
      thought to covary with regularity, yet few studies have examined their co
      occurrence or risk factors that discriminate their trajectories beginning in
      early childhood. METHOD: The present study sought to advance our understanding of
      this issue by examining separate trajectories of overt CP and HAP symptomatology
      among 284 boys from urban, low-income families followed from ages 1.5 to 10. We
      also investigated the co-occurrence of persistent CP and HAP and explored risk
      factors that discriminate CP and HAP trajectories. RESULTS: Four similar
      trajectory groups were identified for both CP and HAP symptoms. Chronic CP was
      differentiated from persistent low CP by risk factors in child, parenting, and
      family domains, while chronic trajectories of HAP were typified by elevated
      maternal depressive symptoms compared to children with persistent low HAP.
      CONCLUSIONS: The findings extend previous research with older children of HAP
      and/or CP, highlighting the effects of proximal family and child risk factors
      that are identifiable in the first two years of children's lives and associated
      with trajectories of disruptive behavior.

PMID- 16108997
TI  - The role of marital discord and parenting in relations between parental problem
      drinking and child adjustment.
AB  - BACKGROUND: Research suggests that children exposed to parental drinking problems
      are at risk for maladjustment. However, the potential impact of drinking problems
      in a community sample and the processes involved in the relationship between
      parental drinking and child outcomes have rarely been examined. METHOD: A
      community sample of 235 mothers and fathers of kindergarten children completed
      measures of problem drinking symptoms, family functioning and child adjustment.
      RESULTS: Model tests indicate that problem drinking was associated with greater
      marital conflict, and that marital conflict was related to ineffective parenting
      which was in turn related to poorer child adjustment. CONCLUSIONS: Even in a
      community sample, parental problem drinking behaviors are associated with reduced
      family functioning that relates to child outcomes.

PMID- 16108998
TI  - Disadvantaged but different: variation among deprived communities in relation to
      child and family well-being.
AB  - BACKGROUND: Disadvantaged communities are increasingly the target for
      interventions. Sure Start was launched in England in 1999 to tackle child poverty
      and improve child and family services, with Sure Start Local Programmes (SSLPs)
      targeted at relatively small areas of marked deprivation. However, they are
      located in a range of different types of communities where they may provide
      services to very different resident populations. They are all disadvantaged but
      underlying that label there are specific patterns of variability, relevant for
      service provision. To evaluate the implementation, impact, and cost-effectiveness
      of SSLPs, or other area-based initiatives, it is important to consider ways in
      which they can be grouped meaningfully according to these patterns. METHOD: Data
      were collected from administrative databases to describe SSLPs in terms of
      demography, deprivation, and aspects of child and family functioning and grouped
      using cluster analysis. RESULTS: Five different 'types' of SSLP community were
      identified, based on their socio-demographic and economic characteristics;
      typified by more, less or average deprivation in relation to all SSLPs, and in
      terms of the proportion of ethnic minority families resident in the areas. The
      groups differ in terms of community measures of child health, educational
      attainment, school disorder and child welfare and their prediction from
      demographic community characteristics. CONCLUSIONS: The groupings have
      implications for service delivery and the evaluation of area-based initiatives.

PMID- 16108999
TI  - Effects of familial risk factors and place of birth on the risk of autism: a
      nationwide register-based study.
AB  - BACKGROUND: The etiology of autism is unknown. A strong genetic component has
      been detected but non-genetic factors may also be involved in the etiology.
      METHODS: We used data from the Danish Psychiatric Central Register and the Danish
      Civil Registration System to study some risk factors of autism, including place
      of birth, parental place of birth, parental age, family history of psychiatric
      disorders, and paternal identity. RESULTS: A total of 943,664 children younger
      than ten years were followed from 1994 to 2001; of those, 818 children developed
      autism. The highest risks of autism were found in siblings of children with
      autism, or Asperger's syndrome and other pervasive developmental disorders
      (PDDs), with relative risks of 22 and 13, respectively. The relative risk of
      autism in the child was about twice as high if the mother had been diagnosed with
      a psychiatric disorder. The risk of autism was associated with increasing degree
      of urbanisation of the child's place of birth and with increasing paternal, but
      not maternal, age. An increased relative risk of 1.4 was found if the mother was
      born outside Europe, and in children of parents who were born in different
      countries. CONCLUSIONS: The highest risk of autism was found in families with a
      history of autism, or Asperger's syndrome and other PDDs in siblings, supporting
      the commonly accepted knowledge that genetic factors are involved in the etiology
      of autism.

PMID- 16109000
TI  - Response reversal and children with psychopathic tendencies: success is a
      function of salience of contingency change.
AB  - BACKGROUND: Previous work has inconsistently reported difficulties with response
      reversal/extinction in children with psychopathic tendencies. METHOD: We tested
      the hypothesis that the degree of impairment seen in children with psychopathic
      tendencies is a function of the salience of contingency change. We investigated
      the performance of children with psychopathic tendencies on a novel probabilistic
      response reversal task involving four conditions with gradated reward-punishment
      contingencies (100-0, 90-10, 80-20 and 70-30; i.e., for the 100-0 contingency,
      responding to one object is always rewarded while responding to the other is
      always punished). RESULTS: In line with predictions, the impairment seen in the
      children with psychopathic tendencies was an inverse function of the salience of
      the contingency change. CONCLUSIONS: We suggest that this data is consistent with
      suggestions of subtle orbital frontal cortex impairment in children with
      psychopathic tendencies.

PMID- 16109001
TI  - Influence of general self-efficacy on the effects of a school-based universal
      primary prevention program of depressive symptoms in adolescents: a randomized
      and controlled follow-up study.
AB  - BACKGROUND: Depressive disorders in adolescents are a widespread and increasing
      problem. Prevention seems a promising and feasible approach. METHODS: We designed
      a cognitive-behavioral school-based universal primary prevention program and
      followed 347 eighth-grade students participating in a randomized controlled trial
      for three months. RESULTS: In line with our hypothesis, participants in the
      prevention program remained on a low level of depressive symptoms, having strong
      social networks. The control group showed increasing depressive symptoms and a
      reduced social network. Contrary to our expectations, students low in self
      efficacy benefited more from the program than high self-efficient students.
      Social network did not mediate the relationship between participation in the
      prevention program and changes in depressive symptoms. CONCLUSIONS: Our results
      show that the prevention program had favorable effects. Further research is
      needed to explore the impact of self-efficacy on the effects of prevention
      programs.

PMID- 16109002
TI  - Selected executive skills in adolescents with recent first episode major
      depression.
AB  - BACKGROUND: To investigate whether recent first episode major depression in
      adolescence is characterised by selected executive difficulties in attentional
      flexibility, behavioural inhibition and decision-making. METHODS: Selected
      executive functions were compared in adolescents with recent (past year) first
      episode major depression (n = 30) and community controls (n = 49). Three
      computerised tests within the CANTAB battery were completed by all subjects (the
      Intra-Dimensional, Extra-Dimensional Set-Shifting task, the Affective Go, No-Go
      task, and the Decision-Making task). RESULTS: Compared with controls, recently
      depressed cases displayed a bias towards negative stimuli with fewer errors on
      sad words as well as being more accurate in their responses to sad targets on the
      Affective Go, No-Go task. Cases also made faster decisions in the context of
      betting more of their available points compared to controls, as indexed by the
      Decision-Making task. These results were not influenced by age, gender, IQ,
      recent mood, severity of depression, medication or comorbidity. CONCLUSIONS:
      Adolescents with recent first episode major depression show greater attention
      towards sad stimuli and more impulsive behaviour when making decisions. They were
      able to switch attentional set to neutral stimuli. This study demonstrates that
      computerised tests for measuring executive functions can be successfully deployed
      in adolescents, and suggests that specific patterns of neuropsychological
      functions may be relatively compromised in first episode major depression. These,
      together with their underlying neural substrates, deserve further investigation
      within this age range.

PMID- 16109003
TI  - The borderline personality diagnosis in adolescents: gender differences and
      subtypes.
AB  - BACKGROUND: This study aimed to identify personality features characterizing
      adolescent girls and boys with borderline personality disorder (BPD) and to see
      whether meaningful patterns of heterogeneity exist among adolescents diagnosed
      with the disorder. METHODS: Two hundred and ninety-four randomly selected
      doctoral-level clinicians described adolescent patients using Axis II rating
      scales and the Shedler-Westen Assessment Procedure-200 for Adolescents (SWAP-200
      A). We used the SWAP-200-A to provide empirically derived descriptions of female
      and male adolescents meeting DSM-IV criteria for BPD (who differed substantially
      in their profiles), and used Q-factor analysis to identify naturally occurring
      groupings of female patients based on shared personality features. RESULTS: The
      symptoms and phenomenology of adolescent girls with BPD are similar to those of
      adults. Adolescent boys meeting BPD criteria have a more aggressive, disruptive,
      antisocial presentation. Although Ns did not permit further analysis of the data
      on adolescent boys, Q-analysis isolated four clinically coherent subgroups of
      girls with BPD: high-functioning internalizing, histrionic, depressive
      internalizing, and angry externalizing. CONCLUSIONS: BPD in female adolescents
      resembles DSM-IV BPD as defined for adults. The operating characteristics of the
      DSM-IV criteria for adolescent boys require further investigation. Empirically
      derived subgroups are similar to those identified in recent research with adult
      females. Differences across subgroups on internalizing and externalizing Child
      Behavior Checklist (CBCL) scales provide preliminary data on the validity of
      subgroups and raise questions about the place of BPD among internalizing and
      externalizing spectrum disorders.

PMID- 16109011
TI  - Insulin initiation in Type 2 diabetes.

PMID- 16109012
TI  - The recruitment crisis in diabetes and endocrinology.

PMID- 16109013
TI  - Diabetic gastroparesis.

PMID- 16109014
TI  - Mitochondrial diabetes.

PMID- 16109015
TI  - Management of diabetes during Ramadan.

PMID- 16109017
TI  - The Fertility Society of Australia Annual Scientific Meeting 2005, 4-7 September
      2005, Christchurch, New Zealand. Abstracts.

PMID- 16109018
TI  - The professionalization of health librarianship in the UK between 1909 and 1978.
AB  - Many strands exist within health information work and during the last century
      librarians in this field identified themselves through special groups or
      associations. This paper focuses on the key role of the Library Association
      Medical Section in the professional development of medical librarians in the
      United Kingdom up to 1978 when it merged with the Library Association Hospital
      Libraries and Handicapped Readers Group to create the Medical, Health and Welfare
      Group. Uniting to form a stronger organization, under the ultimate designation of
      the Health Libraries Group, was part of an evolutionary process. The invention
      and promotion of co-operative schemes, networking and educational opportunities
      for members, the publication of specialized material and the fostering of
      international relationships during the first three-quarters of the century are
      illuminated by personal reminiscences from some of the major participants in the
      field.

PMID- 16109016
TI  - New options for drug treatment of obesity in patients with Type 2 diabetes.

PMID- 16109019
TI  - The way we were: health library life seen through the pages of the Medical
      Library Bulletin of the Thames Regions, 1974-94.
AB  - The Medical Library Bulletin of the Thames Regions reflected the development of
      health-service libraries over the 20 years it existed. Originally begun as a
      practical aid to improving services by encouraging co-operation, improving
      communication and giving instructive advice, it charted the work of health
      service librarians and the growth of their services. The articles contained in it
      covered professional developments and wider political issues as they occurred,
      and illustrated the extension of the librarians' knowledge and skills. Leslie
      Morton, Library Adviser to the British Postgraduate Medical Federation, edited
      almost every issue, starting at a time when there was little guidance or
      professional literature available for health-service librarians.

PMID- 16109020
TI  - Morton's short list of publications on the history of medicine.

PMID- 16109022
TI  - Memorial issue in honour of Leslie T. Morton 1907-2004.

PMID- 16109023
TI  - Leslie Morton; a personal reminiscence.

PMID- 16109024
TI  - A bibliography of Leslie T. Morton.

PMID- 16109025
TI  - The increasing globalization of health librarianship: a brief survey of
      international trends and activities.
AB  - BACKGROUND AND PURPOSE: Throughout his career, Leslie Morton was interested in
      international developments in health librarianship. In memory of the work he did
      in this field, the authors examine current developments in international health
      librarianship and describe some current themes. PROCEDURES: The authors draw from
      their combined experience in international activities and the published
      information available from selected library associations and related
      organizations. FINDINGS: Although many of the major health library associations
      around the world are tackling agendas specific to their own country, issues of
      international concern are emerging in common. These are grouped around
      globalization, partnerships and co-operation, electronic access, especially open
      access, and working with the developing world in a number of different ways. Of
      course, the basis of all of these initiatives is to improve the health of the
      population by providing the best possible access to materials. CONCLUSIONS:
      Professional associations can provide a useful institutional infrastructure for
      addressing issues of international interest. Librarians should encourage their
      associations to develop these international initiatives and to seek out new and
      innovative ways to work together across international boundaries.

PMID- 16109026
TI  - MEDLINE in the UK: pioneering the past, present and future.
AB  - This article provides a brief history of the development of the MEDLINE database
      and its huge impact within the UK, from its inception to the present time. The
      origins of MEDLINE can be traced back to a collection of books in the US Surgeon
      General's Office during the American Civil War and John Shaw Billings' decision,
      during 1867, to make this Library as complete as possible. From these beginnings,
      Index Medicus was developed in the early years of the 20th century, and
      electronic versions of the database began with the computerized on-demand search
      service MEDLARS in 1964 and then via CD-ROM and Internet Grateful Med to the web
      based and free-to-all service, PubMed, in 1997. The response to PubMed was
      immediate and startling with usage increasing from 7 million searches per annum
      in 1996 to 400 million searches per annum in 2001 and the service continues to
      improve. MEDLINE providers are now offering mapping of natural language queries
      to the sophisticated indexing vocabulary (Medical Subject Headings, MeSH) and the
      provision of specific filters for different types of publication to improve
      searching efficiency, as well as links to full-text versions of the papers where
      available. The next steps are likely to involve an increased blurring of database
      and full-text boundaries, incorporating seamless access to the best available
      evidence within MEDLINE and a wide range of other information resources within a
      single search and to an increasing amount of full-text via various open-archive
      initiatives. As ever, the US National Library of Medicine is in the vanguard of
      research and further applications of its MEDLINE database for users within the UK
      will be awaited with great interest.

PMID- 16109027
TI  - Exploring the benefits of user education: a review of three case studies.
AB  - This paper builds on Leslie Morton's vision of enabling users through education
      and training. It describes three different approaches to mediated training for
      medical students and clinicians provided by peers, juniors (i.e. medical
      students) and information specialists (i.e. clinical librarians) and considers
      the benefits to the participants. The training was provided either on a one-to
      one basis or within teams in their work environments (e.g. offices, wards, team
      meetings). The first two projects (peer tutoring and reverse mentoring) suggest
      that contextualized training, using intermediaries, provides the direct benefit
      of cost-effective IT skill development and the indirect benefits deriving from
      the interactions between the trainers and the target groups. The third project,
      the outreach librarian study, provides evidence of both direct benefits (i.e.
      time saved, quality of service, skills acquired, financial savings and improved
      evidence-based medicine implementation) and indirect, long-term benefits relating
      to more social issues (e.g. perceptions of the library, clinical teams, job
      satisfaction and patient interactions). The general conclusion to emerge from
      this review of case studies is that the concept of educational benefits is very
      broad and that empirical studies need to look at both obvious and less obvious
      benefits.

PMID- 16109028
TI  - From the lips of librarians: some thoughts on MLA's oral histories.

PMID- 16109029
TI  - Isidor Fischer's 'Geographical Names in Medical Terminology'.

PMID- 16109030
TI  - Standing on the shoulders of giants: the Leslie Morton Memorial Conference, Royal
      Society of Medicine, London, 25 February 2005.

PMID- 16109032
TI  - Endoderm development in vertebrates: fate mapping, induction and regional
      specification.
AB  - The formation of the vertebrate body plan begins with the differentiation of
      cells into three germ layers: ectoderm, mesoderm and endoderm. Cells in the
      endoderm give rise to the epithelial lining of the digestive tract, associated
      glands and respiratory system. One of the fundamental problems in developmental
      biology is to elucidate how these three primary germ layers are established from
      the homologous population of cells in the early blastomere. To address this
      question, ectoderm and mesoderm development have been extensively analyzed, but
      study of endoderm development has only begun relatively recently. In this review,
      we focus on the 'where', 'when' and 'how' of endoderm development in four
      vertebrate model organisms: the zebrafish, Xenopus, chick and mouse. We discuss
      the classical fate mapping of the endoderm and the more recent progress in
      characterizing its induction, segregation and regional specification.

PMID- 16109033
TI  - Establishment of a chick embryo model for analyzing liver development and a
      search for candidate genes.
AB  - The liver plays a crucial role in metabolism. There is considerable interest in
      how the liver develops, as such knowledge could prove of importance in
      regenerative medicine. However, our understanding of liver development remains
      somewhat limited. We have developed a model system using the chick embryo that is
      cost effective and is easy to manipulate experimentally. We performed four
      fundamental studies: (i) construction of an atlas of the developing chick liver;
      (ii) identification of differentiation marker genes in the developing chick
      embryo; (iii) development of germ-layer specific electroporation; and (iv)
      establishment of organ culture from the developing chick liver. Using this
      system, we have been able to demonstrate the functions of candidate genes within
      a shorter period and in a more cost-effective manner. In parallel with the
      establishment of this system, we examined the expression patterns of genes known
      to be required for organ development in the developing chick embryo in order to
      identify genes also involved in liver development. To date, we have found sixteen
      genes that are expressed in the developing chick liver (GELD, genes expressed in
      liver development). This knowledge will be fundamental to the establishment of
      the basic technology for engineering liver tissue in the future.

PMID- 16109034
TI  - The molecular basis and prospects in pancreatic development.
AB  - Studies on the signaling mechanism that control the specification of endoderm
      derived organs have only recently begun. While many studies revealed genes
      involved in the differentiation, growth and morphogenesis of the pancreas through
      studies of mutant mice, still little is known about how endoderm give rise to
      specific domains. Although many genes are known to have a role in pancreatic
      differentiation, growth and morphogenesis, few genes are known to take part in
      the specification of the pancreas so far. Hallmarks as well as gene markers for
      early development of the pancreas, which are however still very limited, will be
      useful for dissecting early events in pancreatic specification. Here, I give a
      summary on the origin of the dorsal and ventral pancreatic progenitors, signals
      for inductions, and genes so far known to function in pancreatic differentiation.
      I also give a future prospect in the use of ES cells and other experimental
      models, towards a comprehensive understanding of gene networks in the progenitor
      cells or intermediate cell types which arise during various stages of
      differentiation.

PMID- 16109035
TI  - The molecular mechanisms of stomach development in vertebrates.
AB  - The tissue interactions between endodermal epithelium and mesenchyme originated
      from splanchnic mesoderm are essential during the formation of digestive tract.
      In this review, we introduce a series of works to elucidate the molecular
      mechanisms of the epithelial-mesenchymal interaction of stomach development in
      mainly the chicken embryo. We also describe some molecular studies in mouse
      stomach development.

PMID- 16109036
TI  - Functional specification in the Drosophila endoderm.
AB  - The discovery of homeobox gene clusters led us to realize that the mechanisms for
      body patterning and other developmental programs are evolutionally-conserved in
      vertebrates and invertebrates. The endoderm contributes to the lining of the gut
      and associated organs such as the liver and pancreas, which are critical for
      physiological functions. Our knowledge of endoderm development is limited;
      however, recent studies suggest that cooperation between the HNF3/Fork head and
      GATA transcription factors is crucial for endoderm specification. It is necessary
      to further understand the mechanism through which cells become functionally
      organized. Molecular genetic analyses of the Drosophila endoderm would provide
      insights into this issue. During proventriculus morphogenesis, a simple
      epithelial tube is folded into a functional multilayered structure, while two
      functions of midgut copper cells (i.e. copper absorption and acid secretion) can
      be easily visualized. The homeobox gene defective proventriculus (dve) plays key
      roles in these functional specifications.

PMID- 16109037
TI  - Stem-cell-based approaches for regenerative medicine.
AB  - Recent success in transplantation of islets raises the hopes of diabetic patients
      that replacement therapies may be a feasible treatment of their disease. Although
      several lines of evidence suggest that stem cells exist in the pancreas, it is
      still technically hard for us to isolate or maintain the stem cells in vitro. The
      establishment of human embryonic stem (ES) cells has excited scientists regarding
      their potential medical use in tissue replacement therapy. When applied with
      appropriate signals, ES cells can be directed to differentiate into a specific
      cell lineage. Therefore, ES cells are no doubt an excellent source not only for
      regenerative medicine but also for studies of early events of pancreatic
      development, and to portray the pancreatic progenitor cells. Despite many
      attempts that have been tried, the efficiency of differentiation of ES cells into
      islets is still very low. This low efficiency reflects our lack of understanding
      of the intrinsic and extrinsic signals which regulate the developmental processes
      of the pancreas. In this review, I present a summary of recent works on ES cells,
      the identification of pancreatic progenitor cells from the adult pancreas, and
      refer to the possibilities of transdifferentiation from adult stem cells derived
      from other tissues.

PMID- 16109038
TI  - Regulatory targets for transcription factor AP2 in Xenopus embryos.
AB  - The transcription factor AP2 (TFAP2) has an important role in regulating gene
      expression in both epidermis and neural crest cells. In order to further
      characterize these functions we have used a hormone inducible TFAP2alpha fusion
      protein in a Xenopus animal cap assay to identify downstream targets of this
      factor. The most common pattern comprised genes predominantly expressed in the
      epidermis. A second group was expressed at high levels in the neural crest, but
      all of these were also expressed in the epidermis as well as in other tissues in
      which TFAP2alpha has not been detected, suggesting modular control involving both
      TFAP2-dependent and TFAP2-independent components. In addition, a few strongly
      induced genes did not overlap at all in expression pattern with that of
      TFAP2alpha in the early embryo, and were also activated precociously in the
      experimentally manipulated ectoderm, and thus likely represent inappropriate
      regulatory interactions. A final group was identified that were repressed by
      TFAP2alpha and were expressed in the neural plate. These results provide further
      support for the importance of TFAP2alpha in ectoderm development, and also
      highlight the molecular linkage between the epidermis and neural crest in the
      Xenopus embryo.

PMID- 16109039
TI  - Dependence of the timing system regulating the onset of gastrulation on
      cytoplasmic, but not nuclear, activities in the Xenopus embryo.
AB  - This study examines the properties of the timer that regulates the onset of
      gastrulation in the Xenopus embryo. Pre-gastrulation embryos were exposed to
      aphidicolin, vinblastine, 6-dimethylaminopurine (6-DMAP) or urethane. Embryos
      exposed to aphidicolin or vinblastine for 0.5-2 h before the presumptive onset of
      gastrulation, began gastrulation at the same time as control embryos. However,
      those exposed to 6-DMAP or urethane commenced gastrulation significantly later
      than controls. In 6-DMAP- and urethane-treated embryos, the onset of gastrulation
      was retarded by approximately 25% and 120%, respectively. 6-DMAP and urethane,
      but not vinblastine, also lowered the rate of nuclear doubling by 30% and 120%,
      respectively, in late-blastula to early-gastrula embryos. 6-DMAP and urethane
      also lowered the rate of cleavage and cleavage-relevant cytoplasmic cycling by
      30% and 80%, respectively, in cleavage-stage embryos. We propose that cytoplasmic
      activities that can be retarded by 6-DMAP and urethane, but not aphidicolin or
      vinblastine, may be responsible for regulating the onset of gastrulation in
      Xenopus embryos.

PMID- 16109040
TI  - Cytokine-induced stable neuronal differentiation of human bone marrow mesenchymal
      stem cells in a serum/feeder cell-free condition.
AB  - The characteristics and multilineage differentiation potential of bone marrow
      mesenchymal stem cells (BM MSC) remain controversial. This study aimed to
      characterize human BM MSC isolated by plastic adherent or antibody selection and
      their neuronal differentiation potential using growth factors or chemical
      inducing agents. MSC were found to express low levels of neuronal markers:
      neurofilament-M, beta tubulin III, and neuron specific enolase. Under a serum-
      and feeder cell-free condition, basic fibroblast growth factor, epidermal growth
      factor, and platelet-derived growth factor induced neuronal morphology in MSC. In
      addition to the above markers, these cells expressed neurotransmitters or
      associated proteins: gamma-aminobutyric acid, tyrosine hydroxylase and serotonin.
      These changes were maintained for up to 3 months in all bone marrow specimens (N
      = 6). In contrast, butylated hydroxyanisole and dimethylsulfoxide were unable to
      induce sustained neuronal differentiation. Our results show that MSC isolated by
      two different procedures produced identical lineage differentiation with defined
      growth factors in a serum- and feeder cell-free condition.

PMID- 16109041
TI  - Registration, regulation and competence in nursing.

PMID- 16109042
TI  - 'They survive despite the organizational culture, not because of it': a
      longitudinal study of new staff perceptions of what constitutes support during
      the transition to an acute tertiary facility.
AB  - Increasing difficulties of recruitment and retention of nursing staff strongly
      indicate that organizations should identify factors that contribute to successful
      transition of new staff to the workplace. Although many studies have identified
      problems facing new staff, fewer studies have articulated best practices. The
      purpose of this longitudinal study was to ascertain what new staff perceived as
      supportive elements implemented by the organization to assist their integration.
      Sixteen staff in Phase I and 12 staff in Phase II attended focus groups. The
      focus groups at 2-3 months provided specific information, with particular
      emphasis on negative interactions with other staff members and inadequate
      learning assistance and support. Different themes emerged within the focus groups
      at 6-9 months. Staff discussed being 'self-reliant' and 'getting to know the
      system'. Participants indicated that these skills might be beneficial to new
      staff in the development of organizational 'know how' and resourcefulness, rather
      than relying on preceptor support that, unfortunately, cannot be always
      guaranteed.

PMID- 16109043
TI  - The influence of HIV/AIDS on the practice of primary care nurses in Jordan:
      rhetoric and reality.
AB  - The role of nurses in raising community awareness about HIV/AIDS is well
      reported. However, little is known about the practice of Jordanian nurses and the
      role they play in the prevention and control of HIV/AIDS. This interpretive
      ethnographic study sought to illuminate the role of primary care nurses and
      examine the influence of HIV/AIDS on their practice. The study was undertaken in
      Jordan in three rural and three urban primary health-care centres. Data
      collection included participant observation, key informant interviews and
      document analysis. These data informed the development of descriptive
      ethnographic accounts that allowed for the subsequent identification of common
      and divergent themes reflective of factors recognized as influencing the practice
      of the nurse participants. The findings indicate that the rhetoric offered by all
      levels of administration and endorsed in policy is not reflective of the reality
      of practice. Poor resources and educational preparation, a limited nursing skill
      mix and access to professional development, lack of nursing leadership and role
      models, cultural beliefs and geographic isolation are factors that reduced the
      capacity of the primary care nurses to raise awareness and, therefore, influence
      the prevention and control of HIV/AIDS.

PMID- 16109044
TI  - Qualitative evaluation of regular morning meetings aimed at improving
      interdisciplinary communication and patient outcomes.
AB  - Effective interdisciplinary communication is at the heart of clinical decision
      making in contemporary health-care environments. Efforts to enhance communication
      and work processes among nurses and doctors in an infants-and-toddler ward of a
      specialist paediatric hospital led to the establishment of Surgical Morning
      Meetings (SMMs). To evaluate the experiences of nursing and medical team members
      and their perceptions of the changes brought about by the SMM, qualitative
      evaluation of the SMM was undertaken through semistructured interviews. The
      analysis identified four major areas of impact: predictability: a nice way to
      start the day, which captured the ways in which the SMM led to better planning of
      the day's activities, knowledge and perspectives: learning from each other, which
      highlighted the way that ongoing discussions led to greater understanding and
      respect, relationships and support: getting to know you, which reflected the
      benefits derived from greater commitment, and desired outcomes: making a
      difference to staff, children and families. Overall, we believe that initiatives
      as simple as discussions among nurses and doctors can enhance personal and
      professional experience and lead to improved health outcomes for our patients.

PMID- 16109045
TI  - Less money, less care: how nurses in long-term care allocate hours of needed care
      in a context of chronic shortage.
AB  - The average funding of long-term care in Quebec, Canada, currently covers < 70%
      of the care hours required, which means that 30% of needs are unmet. The aims of
      this study were to understand how nurses, when they are in a position to do so,
      assign care hours, which needs are unmet by care dimensions and whether
      dimensions with unmet needs vary with client profiles. One-hundred-and-four
      nurses working in long-term care facilities participated in the study. They
      filled out individual questionnaires containing three case studies in the form of
      vignettes. When obliged to cut 30% of the care hours, the nurses ensured that
      treatment and diagnostic methods were done as prescribed and that vital feeding
      and elimination functions were preserved. However, they made the choice to cut
      some mobility and personal-care activities and, especially, communication with
      patients, families and other professionals. In this, they partly follow the
      theoretical care prioritization approach of Lefebvre and Dupuis, who take into
      account the degree of discomfort caused by the situation, the problem's place in
      Maslow's hierarchy of needs and the availability of a solution. Thus, although
      the choices made by the nurses follow a logical pattern, they could result in
      medium-term deterioration in the functional autonomy of their older patients. The
      overall consequences of these decisions are discussed.

PMID- 16109046
TI  - Tensions and constraints for nurses in hospital-in-the-home programmes.
AB  - Economic necessity constrains health-care expenditure and waiting lists for
      hospital treatments remain high. As a result, more care is delivered via
      alternative means, such as same-day surgery initiatives and home-care programmes.
      Acute care delivered in the home to patients who would otherwise require
      hospitalization is becoming an increasingly acceptable means of treatment. These
      Hospital-in-the-Home programmes offer increased comfort while delivering
      comparable outcomes to many patient groups. The purpose of this paper is to
      generate discussion concerning the tensions that exist for nurses who practice in
      the home under the auspices of acute-care institutions. Data drawn from field
      work that formed part of a critical ethnography is used to generate the
      discussion. The larger research project explored the constructions of the role of
      the nurse in four Hospital-in-the-Home programmes in Victoria, Australia. It will
      be argued that there is significant pressure exerted upon nurses to support the
      imperative to reduce bed days in acute hospitals by transferring people to their
      home. At times, this agenda clashes with the nurses' professional commitment to
      provide holistic patient care, yet the dilemmas are largely unacknowledged and/or
      unrecognized by the nurses despite the tension they generate.

PMID- 16109047
TI  - The effects of a cognitive behavioural therapy programme for self-care on
      haemodialysis patients.
AB  - A nurse-delivered haemodialysis patient education programme incorporating
      cognitive behavioural therapy (CBT) was developed. The effects of the CBT
      programme were compared with those of a standard patient education (SPE)
      programme on patients' salt intake and weight gain using a quasi-experimental
      design. There were 22 participants (11 CBT, 11 SPE) undergoing outpatient
      haemodialysis therapy at one clinic. Daily weight gain rates decreased in the
      intervention period compared with the baseline period in both the CBT and SPE
      groups. This effect lasted for 12 weeks in the CBT group but for only eight weeks
      in the SPE group. In addition, daily salt intake decreased in the intervention
      period compared with the baseline period in both the CBT and SPE groups,
      persisting for 12 weeks. From these results, both programmes were shown to be
      effective, but CBT had a longer effect.

PMID- 16109048
TI  - Parasuicide, self-harm and suicide in Aboriginal people in rural Australia: a
      review of the literature with implications for mental health nursing practice.
AB  - With reports of increased rates of suicide and parasuicide among Aboriginal
      people worldwide, the dual purpose of this background paper is to examine the
      literature on underlying mental health issues, as well as primary and secondary
      actions to try to minimize the risk related to this area among Aboriginal people
      nationally and internationally. The literature review contained in this paper has
      been developed upon the fundamental belief that prevention of mental health
      problems, mental illness and suicide should incorporate understanding of the
      factors that heighten the risk of these occurring and the factors that are
      protective against them, while simultaneously developing, disseminating and
      implementing effective interventions that are culturally and linguistically
      appropriate. To this end, continuity and integration of mental health care for
      rural Aboriginal people is attendant upon a whole-of-community and a whole-of
      government response that respects the metaphor of cultural and linguistic
      experiences, as well as the mental health scope of practice.

PMID- 16109049
TI  - Exposure to rizatriptan during pregnancy: post-marketing experience up to 30 June
      2004.
AB  - Merck & Co., Inc. evaluates outcomes of the use of rizatriptan during pregnancy
      through a Pregnancy Registry in the United States (US) and spontaneous reports
      for pregnancies reported from sources outside the US. Review of the outcomes of
      25 prospective pregnancy reports in the Pregnancy Registry and reports from other
      sources does not suggest that treatment with rizatriptan predisposes patients to
      spontaneous abortions or congenital anomalies. However, the number of reports is
      small. Healthcare providers in the United States are encouraged to report any
      prenatal exposure to rizatriptan by calling the Pregnancy Registry at +1 (800)
      986 8999 or visiting the Registry's website at
      http://www.merckpregnancyregistries.com.

PMID- 16109050
TI  - Facial pain in a neurological tertiary care centre--evaluation of the
      International Classification of Headache Disorders.
AB  - The aim of this study was to examine the diagnostic spectrum of facial pain and
      to evaluate the clinical features relevant to the differential diagnosis in a
      neurological tertiary care centre. This is the first investigation comparing the
      first with the second edition of the International Classification of Headache
      Disorders (ICHD-I, ICHD-II) in consecutively referred patients comprising a broad
      spectrum of disorders without restricting the inclusion to certain diagnoses.
      Studying 97 consecutive patients referred for facial pain, we found trigeminal
      neuralgia or other types of cranial neuralgia in 38% and 39% according to ICHD-I
      and ICHD-II, respectively; persistent idiopathic facial pain was diagnosed in 27%
      and 21%, respectively. The proportion of patients who could not be classified was
      24% in ICHD-I and 29% in ICHD-II. Six per cent of the patients had cluster
      headache or chronic paroxysmal hemicrania, the remaining 5% had various other
      disorders. The agreement between ICHD-I and ICHD-II was very good to perfect. In
      ICHD-II, sensitivity and specificity were similar to ICHD-I, the specificity and
      negative predictive value were imrpoved in single features of trigeminal
      neuralgia, but were widely unchanged in persistent idiopathic facial pain. The
      number of patients who could not be classified was larger in ICHD-II than in ICHD
      I. Modifying the diagnostic criteria for different types of facial pain, in
      particular changes in the criteria of persistent idiopathic facial pain, might be
      helpful in reducing the number of patients with unclassifiable facial pain.

PMID- 16109051
TI  - Calcitonin gene-related peptide in cervicogenic headache.
AB  - Trigeminovascular activation is involved in the pathophysiology of migraine and
      cluster headache. The marker evaluated best for trigeminovascular activation is
      calcitonin gene-related peptide (CGRP) in the cranial circulation. It is unknown
      whether trigeminovascular activation plays any role in cervicogenic headache
      (CEH). The objective of this study was to investigate CGRP plasma levels in CEH
      patients in relation to headache state. To compare plasma CGRP levels between the
      peripheral and the cranial circulation. Blood from both external jugular veins
      and from the antecubital vein was drawn from 11 patients with CEH. Plasma CGRP
      levels were measured by radioimmunoassay. No difference was found between CGRP
      levels assessed on days with and without headache. There was no difference
      between CGRP levels from the symptomatic and the asymptomatic external jugular
      vein and the antecubital vein. There is no evidence for an activation of the
      trigeminovascular system in CEH. In certain cases, clinical differentiation
      between CEH and migraine without aura is difficult. Plasma CGRP levels might
      serve as a biological marker to distinguish the two headache entities.

PMID- 16109052
TI  - Greater occipital nerve block is ineffective in chronic tension type headache.
AB  - Patients with primary headache syndromes often describe a pain distribution, that
      does not respect the trigeminal innervation of the head. In addition to pain in
      frontal areas, innervated by the first (ophthalmic) division of the trigeminal
      nerve, the pain often occurs in occipital parts of the head, innervated by the
      greater occipital nerve, a branch of the C2 spinal nerve root. Anatomical and
      neurophysiological studies in animals suggest a convergence of cervical and
      trigeminal input in the trigeminal nucleus caudalis. Modulation of this pathway
      has been discussed to be of potential benefit in headache disorders. We
      investigated in an open pilot study the effect of bilateral block of the greater
      occipital nerve with 50 mg prilocaine and 4 mg dexamethasone in patients with
      chronic tension type headache. From 15 patients, only one patient described a
      headache relief after initial exacerbation of headache for 2 days. Headache
      intensity was unchanged in 11 patients. In further three patients, the headache
      worsened in the first hours or days after injection. No serious adverse events
      were observed. One patient showed a bradycardia (36/min) after the first
      injection during palpation of the muscles of the neck. Three patients suffered
      pain on the injection site for a few days. Our results indicate that block of the
      greater occipital nerve is not effective in the treatment of chronic tension type
      headache. If at all, rather a 'pro-nociceptive' effect was observed.

PMID- 16109053
TI  - An introduction to the basic principles of health economics for those involved in
      the development and delivery of headache care.
AB  - Against a background of increasing demands on limited resources, health economics
      is gaining an increasing impact on decision making and a basic understanding of
      the subject is important for all those involved in headache research and service
      delivery at whatever level. This paper is not intended as a review of the
      literature in the area of headache economics but discusses some general
      principles of health economics from the perspective of headache, with a focus on
      cost of illness studies and economic evaluation.

PMID- 16109054
TI  - Therapeutic benefit of eletriptan compared to sumatriptan for the acute relief of
      migraine pain--results of a model-based meta-analysis that accounts for
      encapsulation.
AB  - A novel model-based meta-analysis was used to quantify the dose-response
      relationship of sumatriptan and eletriptan for the proportion of patients that
      achieve migraine pain relief up to 4 h after treatment. The proportion of
      patients that became pain free was also evaluated. This analysis includes some
      unique features, allowing comparison of sumatriptan and eletriptan doses that
      have not been directly compared in a head to head study and also permitting
      comparison between the two drugs at multiple time points up to 4 h after
      treatment. Because the analysis allows comparison of response to blinded
      sumatriptan with that to marketed sumatriptan and contains timepoints as early as
      0.5 h, it is especially suited to detection of possible effects of encapsulation
      on sumatriptan's therapeutic effectiveness and thus was employed to assess this
      also. Data from 19 randomized placebo controlled clinical trials were jointly
      analysed using a random-effects logistic regression model. The results of this
      analysis show a significant clinical benefit of eletriptan 40 mg compared to
      sumatriptan 100 mg at any point in time up to 4 h after treatment. The benefit of
      eletriptan 40 mg is greatest around 1.5-2 h after treatment with an absolute
      difference at 2 h of 9.1% (7.4-11.5%) more patients achieving pain relief and
      7.3% (5.8-8.6%) more patient achieving pain free when compared to sumatriptan 100
      mg. An absolute benefit of more than 5% of patients is maintained from 45 min up
      to 4 h after treatment for pain relief and from 1.5 h up to 4 h for pain free.
      Eletriptan 20 mg was superior to sumatriptan 50 mg and similar to sumatriptan 100
      mg for pain relief while it was similar to sumatriptan 50 mg for pain free. The
      benefit of eletriptan 20 mg when compared to sumatriptan 50 mg is greatest around
      1.5-2 h after treatment with an absolute difference at 2 h of 5.0% (2.9-8.1%)
      more patients achieving pain relief. An absolute benefit of more than 3% of
      patients was maintained from 1 h up to 3 h after treatment. No significant
      difference was found between eletriptan 20 mg and sumatriptan 50 mg for the
      fraction of patients that became pain free. No significant effect of
      encapsulation of sumatriptan was found on the time course of response up to 4 h
      after treatment when compared to commercial sumatriptan.

PMID- 16109055
TI  - Eletriptan treatment of migraine in patients switching from barbiturate
      containing analgesics: results from a multiple-attack study.
AB  - The aim of this study was to examine efficacy and tolerability of eletriptan in
      patients switched from barbiturate-containing combinations (Fiorinal), Fioricet.
      Migraineurs (n = 160) meeting IHS criteria, with unsatisfactory response in the
      past year to butalbital-containing combinations, treated up to 16 attacks over 3
      months with eletriptan 40 mg. Assessments included headache response and pain
      free rates and functional impairment at baseline and 2 h postdose, and global
      ratings of treatment satisfaction at 24 h. At 2 h postdose, average headache
      response and pain-free rates were 71% (95% CI, 69-74%) and 37% (95% CI, 35-40%),
      respectively; 68.5% of patients (95% CI, 65-72%) reported functional response.
      Within-patient analysis found no efficacy diminution over time (no tolerance).
      Average headache recurrence rate was 20% (95% CI, 18-23%). Eletriptan was well
      tolerated; 6 (3.7%) patients discontinued due to adverse events. There were no
      serious treatment-related adverse events. We conclude that in poor responders to
      butalbital-caffeine combinations, switching to eletriptan 40 mg was well
      tolerated and efficacious.

PMID- 16109056
TI  - Eletriptan in the early treatment of acute migraine: influence of pain intensity
      and time of dosing.
AB  - This double-blind, placebo-controlled study was designed to evaluate the efficacy
      and tolerability of early treatment of a single migraine attack, when headache
      pain was mild, with two doses (20 mg and 40 mg) of eletriptan. Patients (N = 613;
      female 79%; mean age 39 years) meeting International Headache Society criteria
      for migraine were encouraged, but not required, to utilize early treatment, thus
      providing an opportunity to assess the relative contribution to efficacy of pain
      severity and timing of dose. For the total patient sample (mild-to-severe
      headaches), 2-h pain-free rates were significantly higher than placebo (22%) on
      both eletriptan 20 mg (35%; P < 0.01) and eletriptan 40 mg (47%; P < 0.0001). For
      the cohort of patients who treated their headache when the pain intensity was
      mild, the 2-h pain-free rate on eletriptan 40 mg was 68% compared with 25% on
      placebo (P < 0.0001). Pain intensity at the time of taking eletriptan appeared to
      influence outcome more than the timing of the dose relative to headache onset.
      Eletriptan was well-tolerated, with adverse event rates similar to placebo when
      mild headaches were treated.

PMID- 16109057
TI  - Cluster-like headache secondary to cavernous sinus metastasis.

PMID- 16109058
TI  - Tolosa-Hunt syndrome extending in the cerebello-pontine angle.

PMID- 16109059
TI  - Spontaneous CSF leak complicated by venous thrombosis and dural arteriovenous
      fistula.

PMID- 16109060
TI  - The syndrome of transient headache with neurological deficits and CSF
      lymphocytosis (HaNDL): electrophysiological findings suggesting a migrainous
      pathophysiology.

PMID- 16109061
TI  - Radiofrequency denervation treatment for cervicogenic headache.

PMID- 16109063
TI  - Vertigo and dizziness related to migraine: a diagnostic challenge.

PMID- 16109065
TI  - Abstracts for the 31st Annual Meeting of the International Society for Pediatric
      and Adolescent Diabetes (ISPAD), Krakow, Poland, 31 August - 3 September, 2005.

PMID- 16109066
TI  - Changing trends in epidemiology of type 1 diabetes mellitus throughout the world:
      how far have we come and where do we go from here.

PMID- 16109067
TI  - Epidemics of type 1 diabetes in China.
AB  - OBJECTIVE: The aim of this study was to search for the seasonal and geographic
      variations in epidemics of type 1 diabetes in China. RESEARCH DESIGN AND METHODS:
      Incidence data from 22 type 1 diabetes registration centers across China were
      analyzed. A Poisson regression model with a sine wave function was applied to
      evaluate the seasonal trends. A scan statistic was used to examine the occurrence
      of an epidemic. RESULTS: There was a significant cyclic trend of incidence of
      type 1 diabetes in China. The northern area had a higher incidence rate than the
      southern area. Epidemics were discovered in Dalian and Shenyang from late 1992 to
      late 1993. CONCLUSIONS: There was a strong association of climate and incidence
      of type 1 diabetes in China, whereby the incidence was higher in the colder areas
      and in the winter months. Evidence of epidemics existed in two centers in 1992-
      1993. It is critical to identify the epidemics early and determine the causes of
      epidemics.

PMID- 16109068
TI  - Hyperglycemic hyperosmolar non-ketotic syndrome in children with type 2
      diabetes*.
AB  - OBJECTIVE: Hyperglycemic hyperosmolar non-ketotic (HHNK) syndrome is thought to
      be a rare entity in the pediatric population, associated with significant
      mortality based on case reports in the literature. As obesity and type 2 diabetes
      in childhood grow in prevalence, such related complications may also increase.
      This study will serve to provide updated information regarding typical clinical
      course and sequelae of HHNK syndrome in childhood. METHODS: Patients diagnosed
      with type 2 diabetes at Children's Hospital of Philadelphia (CHOP) over a period
      of 5 yr were screened retrospectively for any laboratory evidence of previous
      episodes of HHNK syndrome. The standard diagnostic criteria of blood glucose >600
      mg/dL and serum osmolality >330 mOsm/L with only mild acidosis (serum bicarbonate
      >15 mmol/L and small ketonuria 15 mg/dL or less) were utilized. RESULTS: The
      records of all patients with type 2 diabetes mellitus (DM) diagnosed over a 5-yr
      period were reviewed (n=190). Seven patients were found to have one episode of
      HHNK syndrome by diagnostic criteria (five males, mean age at presentation 13.3
      yr, age range 10.1--16.9 yr), yielding a frequency of 3.7%. All were African
      American. HHNK syndrome was the clinical presentation at diagnosis of new onset
      diabetes for all seven children. Three of seven children had a previously
      diagnosed developmental delay. The average Glasgow Coma Scale (GCS) score at
      presentation was 13 (range 9--15). Mean body mass index (BMI) at presentation was
      32.7 kg/m(2) (n=6). Mean serum osmolality was 393 mOsm/L (n=7), and mean blood
      glucose was 1604 mg/dL (n = 7). The average time until mental status returned to
      baseline among survivors was 3 d (range 1--7 d). The average number of hospital
      days for survivors was 10 (range 5--24 d). Four of seven patients had an
      uncomplicated course. One patient developed multisystem organ failure and died on
      hospital day 4. The case fatality rate was 14.3% (one of seven). Survivors had no
      appreciable neurodevelopmental sequelae. CONCLUSIONS: This retrospective chart
      review provides updated information regarding the entity of HHNK syndrome in
      children. This study supports the need for increased awareness of type 2 diabetes
      in children so that morbidity and mortality related to HHNK syndrome can be
      prevented.

PMID- 16109069
TI  - Newborn HLA-DR,DQ genotype screening: age- and ethnicity-specific type 1 diabetes
      risk estimates.
AB  - OBJECTIVE: Certain human leukocyte antigen (HLA)-DR,DQ genotypes have been
      associated with type 1 diabetes mellitus (T1DM) risk, although it is unknown
      whether the association is due to alleles, haplotypes, genotypes, the formation
      of heterodimers, or all of the above. To characterize the role of the HLA-DR,DQ
      genotype and ethnicity on the onset age of T1DM, we analyzed these factors in
      patients with T1DM and the general population. METHODS: One thousand three
      hundred twenty-two well-characterized patients with T1DM were compared with 3339
      children from the general population of Denver, Colorado, USA. Because of the
      extensive available data across age and ethnic groups, this study population is
      unique. RESULTS: The HLA-DR3/4,DQB1*0302, DRX/4,DQB1*0302 (where X=1, 4, 8, and
      9), and HLA--DR3/3 genotypes were associated with T1DM, supporting previous
      research. Additionally, the DR3/9 genotype showed a positive association with
      T1DM, which has not previously been described in Caucasian populations. The HLA
      DR3/4*0302 genotype was most strongly associated with T1DM in diabetic
      individuals with the youngest onset age. Genotype frequencies were similar
      between Hispanics and non-Hispanic whites, except for the DR3/3 genotype, which
      was more likely to be found in non-Hispanic whites. CONCLUSIONS: These results
      indicate that there are multiple alleles and genotypes associated with T1DM and
      that the risk associated with different genetic markers depends on the age of
      disease onset, suggesting that some markers may be involved in more rapid disease
      progression.

PMID- 16109070
TI  - Aerobic exercise capacity in normal adolescents and those with type 1 diabetes
      mellitus.
AB  - OBJECTIVE: To compare the aerobic exercise capacity between normal adolescents
      and those with type 1 diabetes mellitus (T1DM). METHODS: An experimental group
      with 72 individuals diagnosed with T1DM aged 9--20, time from diagnosis 4.9 +/-
      3.6 yr, without clinical cardiopulmonary disease or anemia and a control group
      (C) with 46 healthy individuals aged 10--18, matched by age, weight, height, body
      mass index, and lean and fat mass (kg), underwent an incremental aerobic
      exercising test on a motorized treadmill, where gas exchange variables - peak
      pulmonary ventilation (VE), peak oxygen consumption (VO(2)), and carbon dioxide
      production (CO(2)) - as well as their heart rate (HR) and time to exhaustion were
      recorded. RESULTS: Body mass composition had no significant difference between
      experimental and control groups, and male and female subjects had similar
      exercising performances. The mean of hemoglobin A1c in the control group was
      5.2+/- 0.9% and in the diabetic group 8.1+/- 2.2%; p=0.000. The patients with
      T1DM showed lower levels of aerobic capacity than the control group. Their
      respective values for each variable were as follows: (i) maximal VO(2) (T1DM:
      41.57+/-7.68 vs. C: 51.12+/- 9.94 mL/kg/min; p< 0.001) and (ii) maximal VE (T1DM:
      76.39+/-19.93 vs. C: 96.90 +/- 25.72 mL/kg/min; p< 0.001). Patients with T1DM
      also had an earlier time to exhaustion (T1DM: 8.75+/-1.60 vs. 10.82+/-1.44 min).
      CONCLUSIONS: Adolescent patients with T1DM showed a reduced aerobic exercising
      capacity when compared to healthy peers matched to anthropometric conditions.
      This potential condition should be taken into consideration by the time of
      evaluation of the aerobic performance of these patients with glycemic control
      level.

PMID- 16109071
TI  - Use of insulin glargine in children under age 6 with type 1 diabetes.
AB  - AIM: Children under 6 yr have the highest incidence of severe hypoglycemia (SH)
      and the greatest likelihood of brain damage from SH. The purpose of this study is
      to evaluate the use of insulin glargine (Lantus in children under age 6 with type
      1 diabetes (T1D). METHODS: The electronic medical records were reviewed for
      patients under age 6 during the first 6 months of insulin glargine therapy and
      compared with age, sex, and duration of diabetes for matched control patients on
      neutral protamine Hagedorn (NPH) insulin. Data from 128 subjects (32 male pairs
      and 32 female pairs) were collected relating to the incidence of severe and non
      severe hypoglycemic events, hemoglobin A1c (HbA1c) values, body mass index (BMI),
      and daily insulin dose. Additionally, parents were asked to complete a diabetes
      Quality of Life (QoL) survey. RESULTS: In the 6 months before the study period,
      the glargine group had 16 SH events compared with three in the 6 months post
      glargine. The comparison (NPH) group had seven and six SH events in their
      respective 6-month periods. Nighttime SH events in the glargine group decreased
      from 12 prestudy events to one during the study period. The average daily insulin
      dose in the glargine group was higher than that in the NPH group (0.8+/- 0.2 vs.
      0.7+/- 0.2 U/kg/day; p=0.03). The HbA1c values, BMI, and QoL responses were not
      significantly different between the two groups. CONCLUSIONS: SH was decreased,
      particularly at night (from 12 episodes to one), after the introduction of
      glargine in young children with T1D.

PMID- 16109073
TI  - Adult-like but regressive increase of intima-media thickness and roughness in a
      child with type 1 diabetes.
AB  - A 12-yr-old Kosovo-Albanian boy with insufficiently controlled type 1 diabetes
      since his second year of life developed severely increased intima-media thickness
      (IMT) and roughness (IMR) of the common carotid artery (CCA): max/mean
      IMT=0.81/0.68 mm and IMR=0.048 mm. Intima-media thickening, comparable with that
      in a 50- to 60-yr-old healthy adult, decreased within 41 months (max/mean carotid
      IMT=0.72/0.56 mm and IMR=0.036 mm) by intensive treatment of diabetes. Moyamoya
      disease (MMD), complicated by cerebral infarction, occurred coincidentally but
      regressed within 6 months. This case report points out that (i) chronic
      hyperglycemia in childhood may lead to adult-like increase of carotid IMT/IMR as
      early signs of subclinical atherosclerosis, (ii) increased carotid IMT/IMR may be
      regressive by intensive diabetes control, and (iii) a screening examination for
      carotid IMT/IMR should be considered in patients at high risk of atherosclerosis.

PMID- 16109072
TI  - Possible impact of plasma RNase activity on immune dysfunction in juvenile
      diabetes mellitus.
AB  - AIM: The ribonuclease (RNase) family represents important enzymes used widely in
      biomedical and biotechnological applications, as well as for diagnostic and
      therapeutic purposes. This study was undertaken to test the possibility that
      plasma alkaline RNase (free or inhibitory bound) determination may be useful in
      studying the dysregulation of nucleic acid and oligonucleotide metabolism as a
      possible pathogenetic mechanism in development of immune dysfunction in juvenile
      diabetes mellitus. PATIENTS AND METHODS: Children with type 1 diabetes (n=32, age
      group of 5--14 yr), together with age-matched control subjects (n=35), were
      enrolled in the study. None had microvascular complications. According to the
      metabolic regulation of the disease and the hemoglobin A1c (HbA1c) level, all
      patients were divided into two groups (HbA1c<7.5% and HbA1c>7.5%). According to
      the duration of diabetes, diabetic children were divided into two groups:
      duration of diabetes less than 1 yr and duration of diabetes greater than 1 yr.
      The control group consisted of age-matched subjects (n=35; 15 girls and 20 boys)
      who were clinically healthy. The activity of free and inhibitory-bound RNase and
      the level of acid soluble nucleotides were measured in heparinized plasma.
      RESULTS: The inhibitory-bound enzyme activity was higher in diabetic children,
      followed by sharply decreased free enzyme, especially in the group with the level
      of HbA1c above 7.5%. Recent-onset diabetic patients had lower free RNase activity
      compared with those with longer duration of the disease. The amount of pre
      existing acid-soluble oligonucleotides was significantly increased in diabetic
      children, especially in those with poor metabolic control. CONCLUSION: Our
      observed preliminary results may suggest a hypothesis that a persistent increase
      of oligonucleotide fragments, most probably due to insufficient RNase activity,
      may lead to T-cell hyperactivity in type 1 diabetes through the activation of
      toll-like receptors (TLRs). The measurement of RNase(s) activity (free,
      inhibitory-bound, or specific toward different substrates), together with the
      well-known immunobiochemical parameters of diabetes, may help further efforts in
      identifying a disease-specific early biological marker of immunity dysfunction in
      juvenile diabetes.

PMID- 16109074
TI  - Utility of murine models for the study of spontaneous autoimmune type 1 diabetes.

PMID- 16109075
TI  - Intradialytic serum protein concentrations differ between nightly nocturnal and
      conventional haemodialysis.
AB  - AIM: Nocturnal haemodialysis (NHD) is a new haemodialysis (HD) modality that has
      been shown to have many benefits when compared with conventional haemodialysis
      (CHD). Previous results from our NHD programme have demonstrated a 7% fall in the
      postdialysis serum albumin concentration when compared with the pre-HD levels. A
      similar, physiological, 9% haemodilution of albumin is seen in normal individuals
      on assuming a supine posture. METHOD: In this observational study, the
      intradialytic change in the concentration of 11 serum proteins (total protein,
      albumin, alkaline phosphatase, gamma glutamyl transferase, alanine transaminase,
      amylase, transferrin, complement factors 3 and 4, free thyroxine and C-reactive
      protein (CRP)) was measured in 10 patients on NHD and in 10 age- and sex-matched
      controls on CHD. The ultrafiltration rate (UFR) was also recorded. RESULTS: We
      demonstrated an intradialytic fall in the total protein (0.63%), albumin (2.40%),
      alkaline phosphatase (1.84%), amylase (8.82%), complement factor 3 (2.73%) and
      CRP (8.19%) in patients on NHD. This was of a lesser magnitude than that
      occurring in the pilot study but still approximated the physiological fall in
      serum proteins occurring with overnight recumbency in normal individuals. In
      contrast, all serum proteins measured rose during CHD, reflecting intravascular
      volume contraction and haemoconcentration. The UFR was significantly lower in NHD
      than CHD (234.52+/-20.90 mL/h vs 435.38+/-38.44 mL/h, P<0.001). CONCLUSION: We
      concluded that NHD is a modality that facilitates the use of a low UFR and hence
      the slow removal of volume which, in turn, results in a minimal perturbation of
      the normal recumbent volume distribution mechanism and the partial preservation
      of the normal physiological response to recumbency of the serum protein
      concentration.

PMID- 16109076
TI  - Relationship between sleep complaints and proinflammatory cytokines in
      haemodialysis patients.
AB  - BACKGROUND: Sleep complaints are common in end-stage renal disease. We aimed to
      investigate the relationship between sleep-related complaints and inflammatory
      cytokines in haemodialysis (HD) patients, and also the effects of HD on sleep
      patterns and cytokine levels. METHODS: Predialysis serum interleukin-1beta (IL
      1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels
      in nine patients with sleep complaints were compared with those of nine patients
      without sleep complaints and nine healthy controls. Patients with sleep
      complaints underwent polysomnography the night after HD and the following night.
      RESULTS: Patients with sleep complaints had significantly higher predialysis IL
      1beta levels compared with those without and healthy controls (P=0.004 and
      P=0.000, respectively). They also had higher predialysis IL-6 and TNF-alpha
      levels than those without sleep complaints; however, the difference was not
      significant. Patients without sleep complaints had higher mean IL-6 and TNF-alpha
      and similar mean IL-1beta levels compared with healthy controls (P=0.001,
      P=0.024, P=0.26, respectively). Obstructive sleep apnoea syndrome (OSAS) was
      found in six out of nine (66%) patients with sleep complaints. Sleep architecture
      and cytokine levels did not differ between the two nights. The mean serum IL
      1beta, IL-6 and TNF-alpha levels did not differ in the pre- and post
      polysomnographic samples. There was no correlation between IL-1beta, IL-6 or TNF
      alpha levels and the apnoea-hypopnoea index. CONCLUSIONS: Proinflammatory
      cytokines, IL-1beta in particular, might be associated with sleep complaints in
      HD patients. OSAS is not uncommon in HD patients with sleep-related complaints
      and sleep architecture does not appear to be effected by the HD procedure itself.

PMID- 16109077
TI  - Efficacy and safety of oral versus intravenous ascorbic acid for anaemia in
      haemodialysis patients.
AB  - BACKGROUND: Intravenous (i.v.) ascorbic acid (AA) improves anaemia in iron
      overloaded, erythropoietin (rEPO) hyporesponsive haemodialysis patients. While
      oral AA is readily attainable, the efficacy and safety of oral versus i.v. AA has
      not been examined. METHODS: We conducted an open-label randomised parallel study
      on the effects of 8 weeks of 250 mg oral AA (n=10) compared with 250 mg i.v. AA
      (n=11) 3x/week on haemoglobin (Hb), ferritin and rEPO dose in 21 iron-overloaded
      haemodialysis patients. We also examined the effect of 3 months of 500 mg oral AA
      3x/week (n=70) compared with no treatment (n=83) on Hb, ferritin and rEPO dose in
      153 haemodialysis patients. RESULTS: Patients had severe AA deficiency (mean
      2.2+/-SE 0.4 mg/L; normal range, 4.0-14.0). Following treatment, the plasma AA
      level increased (P<0.001), but was not significantly different between the
      groups. There was no change in Hb, iron availability and rEPO dose with oral or
      i.v. AA. There was a significant increase in serum oxalate but no significant
      changes in left ventricular function or renal calculi formation. In the second
      study, oral AA had no effect on Hb, rEPO dose and ferritin in the whole group and
      a subgroup of 30 with anaemia. CONCLUSION: Haemoglobin and iron availability did
      not improve following oral or i.v. AA in this select small group of iron
      overloaded haemodialysis patients or in a larger population of haemodialysis
      patients given oral AA at a higher dose and for a longer duration. AA
      supplementation may still be warranted in view of severe AA deficiency in
      haemodialysis patients.

PMID- 16109078
TI  - Encapsulating peritoneal sclerosis in paediatric peritoneal dialysis patients.
AB  - Encapsulating peritoneal sclerosis (EPS) is a serious complication of chronic
      peritoneal dialysis (CPD). In contrast to the adult population, there are few
      studies regarding EPS in paediatric CPD patients, and the majority of reported
      patients are from Japan. The aim of the present report is to define the incidence
      of EPS in our paediatric CPD patients and to describe the clinical and laboratory
      characteristics. A total of 104 paediatric patients were followed from November
      1989 to November 2003 and two were diagnosed as EPS (1.9%). The dialysis periods
      of these patients were 45 and 53 months with 6 and 8 peritonitis episodes,
      respectively. Clinical signs of EPS developed 7 and 14 days after the removal of
      the dialysis catheter, and CPD was replaced by haemodialysis because of
      persistent peritonitis. One patient was well after surgical management but died 6
      months later. The second patient who was treated with prednisolone remained well
      at 16 months. In conclusion, EPS is a rare but important complication of CPD. We
      recommend that all patients on CPD who develop ultrafiltration failure be
      evaluated radiologically for the occurrence of EPS. Management should be tailored
      to the individual patient.

PMID- 16109079
TI  - Octreotide therapy for chylous ascites in a chronic dialysis patient.
AB  - Chylous ascites, a rare complication in patients receiving continuous peritoneal
      dialysis, often presents with turbid dialysate. This characteristic makes it
      frequently confused with peritonitis. Conservative treatments including bowel
      rest and dietary intervention with medium chain triglycerides are advised by many
      authors in the literature. However, this approach usually takes a long time
      before the lymphorrhagia are eventually resolved. Here, a case of chylous ascites
      that was successfully treated with subcutaneous octreotide, a somatostatin
      analogue, is reported. By shortening the bowel rest period, this treatment avoids
      the nutritional and immunological adverse effects. A series of peritoneal
      equilibrium tests were performed after administration of octreotide and the
      results showed that octreotide did not alter the peritoneal function in the short
      term. Therefore, subcutaneous octreotide administration is a safe and effective
      therapy in peritoneal dialysis patient with chylous ascites.

PMID- 16109080
TI  - Noscapine suppresses angiotensin converting enzyme inhibitors-induced cough.
AB  - BACKGROUND: Dry cough is a common side-effect of the angiotensin converting
      enzyme inhibitors (ACEI) and is a major limiting factor of their use. It has been
      suggested that ACEI cause this side-effect by potentiation of the bradykinin
      effect. Previous work in our laboratory has shown that noscapine, an antitussive
      drug, inhibits the effect of bradykinin. METHODS: To investigate the effect of
      noscapine on ACEI-induced cough, 611 hypertensive patients who were being treated
      with ACEI were evaluated for the incidence of persistent dry cough. RESULTS: A
      cough had developed in 65 (10.6%) patients, two (3.1%) of whom also had severe
      respiratory distress that required hospitalisation and immediate discontinuation
      of the ACEI. Forty-two (64.6%) patients had developed a mild cough and 21 (32.3%)
      patients had developed a moderate to severe cough. The patients with moderate to
      severe cough received 15 mg of noscapine, orally three times daily, while they
      continued ACEI. Noscapine effectively resolved the cough in 19 (90%) patients
      within 4-9 days of starting treatment. CONCLUSION: Noscapine, possibly by
      inhibition of bradykinin synthesis, eliminates ACEI-induced cough in the majority
      of patients and allows them to continue with ACEI therapy.

PMID- 16109081
TI  - Role of impaired peritubular capillary and hypoxia in progressive interstitial
      fibrosis after 56 subtotal nephrectomy of rats.
AB  - AIM: To investigate the potential role of peritubular capillary (PTC) loss and
      subsequent hypoxia as a pathogenic factor in interstitial fibrosis after renal
      ablation in rats. METHODS: PTC loss and tubulointerstitial hypoxia in remnant
      kidney rats (SNTx group), sham-operated rats (sham group) and normal animals
      (normal group) were assessed by peritubular CD141-positive staining lumina and
      tubulointerstitial hypoxia-inducible factor alpha subunit 1 (HIF-1alpha)
      expression, respectively, at the time points of week 3, week 6 and week 12. The
      related cardinal factors contributing to interstitial fibrosis, such as
      transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha
      SMA) were also evaluated and analysed in the context of progressive PTC loss.
      Expression of TGF-beta1 mRNA in cultured renal tubular epithelial cells (MDCK
      cells) exposed to hypoxia was also investigated. RESULTS: PTC loss and
      tubulointerstitial hypoxia were noted even in the early stage (week 3) when the
      interstitial fibrosis was mild, and were persistent in the process of developing
      interstitial fibrosis. An in vitro study showed that hypoxia enhanced TGF-beta1
      mRNA expression in the MDCK cells. CONCLUSION: PTC loss or hypoxic milieu in the
      tubulointerstitium is a pathological event, which may contribute to the
      developing interstitial fibrosis mediated by direct hypoxic effects and via
      hypoxia-induced TGF-beta1 expression.

PMID- 16109082
TI  - Renal ultrasound findings in an Australian Aboriginal population with high rates
      of renal disease.
AB  - BACKGROUND: Rates of albuminuria and haematuria are extremely high with
      haematuria prevalence as high as 30-50% in adults of some Aboriginal groups.
      Dipstick testing of urine is routinely carried out in Aboriginal communities and
      as part of school screening programmes. Evaluation of the many affected
      individuals has traditionally included renal ultrasound examination, which
      involves considerable expense and logistic problems in remote communities. The
      present study was conducted to evaluate the usefulness of ultrasound in this
      setting. METHODS: A population survey was conducted in a remote community. Urine
      dipstick analysis and the albumin:creatinine ratio (ACR; g/mol) were measured in
      1440 people over 5 years of age (89% of the eligible population), and a detailed
      renal ultrasound examination was performed in a random subset of 647 people
      (41.1% of the whole group), 276 aged 5-19 years and 371 over 20 years of age.
      RESULTS: Urine dipstick proteinuria (>1+) was present in 8.5% (23/271) of those
      aged 5-19 years and 37.9% (132/348) in those aged over 20 years; pathological
      albuminuria (ACR>3.4) was present in 7.6% (21/276) and 54.7% (203/371),
      respectively, and isolated haematuria was present in 7.7% (21/273) and 11.5%
      (40/347), respectively. Eight ultrasound abnormalities were found. Ultrasound
      findings did not change the management of any individual. CONCLUSION: Renal
      ultrasound added little to the evaluation of people with asymptomatic proteinuria
      or haematuria in this setting. In this scenario, ultrasound examination could be
      reserved for the cases with an unusual presentation where findings are likely to
      influence the prognosis or treatment, or in preparation for a renal biopsy.

PMID- 16109083
TI  - Podocyte biology in human disease.
AB  - The podocyte is a highly specialized cell that plays a key role in regulating the
      glomerular filtration barrier. A number of advances have been made in recent
      years, linked to the discovery of single-gene defects in hereditary glomerular
      disease, which highlight the role of this cell in preventing proteinuria. This
      article reviews the molecular biology of the podocyte, focusing on known genetic
      abnormalities.

PMID- 16109084
TI  - Glomerulonephritis due to antineutrophil cytoplasm antibody-associated
      vasculitis: an update on approaches to management.
AB  - A patient with antineutrophil cytoplasm antibody-associated vasculitis frequently
      has multisystem disease and might present to a range of medical specialities. The
      manifestations that result in the greatest burden of morbidity and mortality are
      renal and pulmonary disease. In this review we will focus on rapidly progressive
      glomerulonephritis due to vasculitis, with specific reference to recent advances
      in our understanding of pathogenesis. The current standard of care for managing
      renal vasculitis, be it mild, moderate or severe, has largely been established in
      clinical trials of prednisolone, cyclophosphamide, methotrexate, azathioprine and
      plasma exchange. In addition to these, newer therapies such as mycophenolate
      mofetil and infliximab are being used more frequently. We will review the role of
      each of these approaches to management of small vessel vasculitis in 2005.

PMID- 16109085
TI  - Polymorphisms of the angiotensin converting enzyme and angiotensin II type 1
      receptor genes and renal scarring in non-uropathic children with recurrent
      urinary tract infection.
AB  - AIM: The aim of this study was to investigate whether the angiotensin converting
      enzyme (ACE) and angiotensin II type 1 receptor (A1166C) gene polymorphisms were
      associated with the renal scar formation secondary to recurrent urinary tract
      infection in children without uropathy. METHODS: The polymorphisms were
      investigated by polymerase chain reaction in 97 children (81 females, 16 males;
      age, 2.5-13 years) with recurrent urinary tract infection and 100 healthy
      controls as a single centre study. Children with vesicoureteral reflux, bladder
      dysfunction and other uropathies were excluded. The dimercaptosuccinic acid
      (DMSA) scan performed at least 3 months after a proven urinary tract infection
      and the result of the last DMSA was taken into consideration. RESULTS: Renal
      scarring was found in 30 patients (30.9%) using DMSA scan. The number of urinary
      tract infection attacks was significantly higher in patients with renal scarring
      compared with children without scarring (P<0.05). The follow-up period and
      male/female ratio of patients with or without renal scarring was similar
      (P>0.05). Age at the first urinary tract infection was lower in the group with
      scarring. The ACE insertion/deletion genotype distribution and D allele frequency
      were similar between patients and controls (P>0.05), and in patients with renal
      scarring and those without renal scarring. Also, the angiotensin II type 1
      receptor gene polymorphism was not associated with renal parenchymal damage
      (P>0.05). CONCLUSION: The results indicated that the ACE insertion/deletion and
      angiotensin II type 1 receptor gene polymorphisms were not independent risk
      factors for renal scar formation in recurrent urinary tract infection of
      paediatric patients without uropathy.

PMID- 16109086
TI  - Huge renal angiomyolipomas in tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominance disorder with variable
      penetrance. Renal angiomyolipoma (AML) is one of the commonest urological
      manifestations. These lesions may cause significant morbidity and mortality. We
      report two patients with multiple and huge renal angiomyolipomas presenting with
      gross haematuria. They subsequently underwent unilateral nephrectomy. The
      difficulty in diagnosis and controversies in management will be briefly
      discussed.

PMID- 16109087
TI  - Lifestyle modification and progressive renal failure.
AB  - There is increasing evidence that lifestyle factors impact on the risk of
      developing chronic kidney disease (CKD) and the risk of progression of CKD.
      Equally important is the consideration that patients with CKD are more likely to
      die from cardiovascular disease than to reach the stage of end-stage renal
      failure. It is advantageous that manoeuvres that interfere with progression at
      the same time also reduce the risk of cardiovascular events. Lifestyle factors
      that aggravate progression include, among others, smoking, obesity and dietary
      salt intake. Alcohol consumption, according to some preliminary information, has
      a bimodal relationship to cardiovascular risk and progression, with moderate
      consumption being protective.

PMID- 16109088
TI  - Effects of short-term alendronate on bone mineral density in haemodialysis
      patients.
AB  - BACKGROUND: Low bone mineral density (BMD) is common in dialysis patients. Low
      BMD predicts the fracture risk in the general population. Bisphosphonate therapy
      improves BMD and lowers the fracture risk in many populations, but has not been
      tested in dialysis patients because of concerns about toxicity. In this
      investigation, the effect of a short course of alendronate on BMD in
      haemodialysis (HD) patients is evaluated. METHODS: Thirty-one healthy HD patients
      were randomized to placebo versus 40 mg alendronate, taken once a week for 6
      weeks. Hip and lumbar spine BMD were measured by dual energy X-ray absorptiometry
      at baseline and at 6 months. Osteocalcin, parathyroid hormone, calcium,
      phosphorous and alkaline phosphatase levels were assayed at baseline and at 1, 3
      and 6 months. RESULTS: The BMD and T-scores in specific regions of the hip were
      stable in the treatment group and decreased in the placebo group (P=0.05). The
      lumbar spine density increased minimally in both groups. In the treatment group,
      osteocalcin levels declined significantly at 1 month (P<0.05) and remained low.
      The main side-effect in the alendronate group was occurrence of gastroesophageal
      reflux symptoms in three subjects. CONCLUSIONS: Low-dose alendronate,
      administered for a limited duration, appears to be well tolerated in dialysis
      patients. The BMD and T-scores declined at certain hip regions in the placebo
      group over 6 months, while remaining stable in the treatment group, suggesting a
      bone-preserving effect of alendronate. Further studies of longer duration, and
      including examination of bone histology, are needed to assess whether
      bisphosphonates can be used to preserve BMD in dialysis patients.

PMID- 16109089
TI  - Different regional dynamics of end-stage renal disease in Japan by different
      causes.
AB  - BACKGROUND: We recently showed that there were clear regional differences in the
      dynamics of end-stage renal disease (ESRD) within Japan, which has an ethnically
      homogenous population. We speculate on the reason for these regional differences
      by correlating the regional distributions in the incidence of ESRD due to each of
      the following individual causes of ESRD: chronic glomerulonephritis (CGN),
      diabetic nephropathy (DMN) and polycystic kidney disease (PKD). METHODS: The
      number of ESRD patients entering maintenance dialysis therapy due to individual
      causes of renal disease in each prefecture was reported annually for a 6-year
      period by the Japanese Society for Dialysis Therapy. After combining data from
      several prefectures into 11 geopolitical regions in Japan, the mean annual
      incidence of ESRD across the 11 regions was correlated among the three causes of
      ESRD. RESULTS: There were significant regional differences in the incidence of
      ESRD due to CGN (P<0.0001) and DMN (P=0.0015), the distributions of which were
      similar to each other across the 11 regions. In contrast, no regional differences
      were found in the incidence of ESRD due to PKD (P=0.6) as the major genetic
      disorder of the kidneys, suggesting that genetic backgrounds are relatively
      uniform throughout Japan. The regional distributions due to PKD were not
      correlated with those due to other causes: CGN and DMN. CONCLUSION: Risk factors
      common to nephropathy progression, rather than an underlying disease incidence
      and genetic predisposition, might contribute to regional differences in the
      overall ESRD incidence in Japan. Other possibilities such as the prevalence of
      underlying diseases, and acceptance or rejection rates into treatment programmes
      must be considered further for better explanations.

PMID- 16109090
TI  - Impact of obesity on renal transplant outcomes.
AB  - Obesity is a frequent and important consideration to be taken into account when
      assessing patient suitability for renal transplantation. In addition,
      posttransplant obesity continues to represent a significant challenge to health
      care professionals caring for renal transplant recipients. Despite the vast
      amount of evidence that exists on the effect of pretransplant obesity on renal
      transplant outcomes, there are still conflicting views regarding whether obese
      renal transplant recipients have a worse outcome, in terms of short- and long
      term graft survival and patient survival, compared with their non-obese
      counterparts. It is well established that any association of obesity with reduced
      patient survival in renal transplant recipients is mediated in part by its
      clustering with traditional cardiovascular risk factors such as hypertension,
      dyslipidaemia, insulin resistance and posttransplant diabetes mellitus, but what
      is not understood is what mediates the association of obesity with graft failure.
      Whether it is the higher incidence of cardiovascular comorbidities jeopardising
      the graft or factors specific to obesity, such as hyperfiltration and
      glomerulopathy, that might be implicated, currently remains unknown. It can be
      concluded, however, that pre- and posttransplant obesity should be targeted as
      aggressively as the more well-established cardiovascular risk factors in order to
      optimize long-term renal transplant outcomes.

PMID- 16109091
TI  - Biopsy of potential cadaveric renal allografts at the time of retrieval.
AB  - Biopsy of cadaver renal allografts may aid in the assessment of marginal
      allografts. However, the use of this approach is not clear. This study presents
      the outcome of institution of a protocol for back table biopsy of renal
      allografts during organ procurement. METHODS: Data from Lifelink Organ Donation
      Network records and the ANZDATA registry were analysed. RESULTS: The biopsy rate
      of renal allografts increased from 0.8% to 15.6% (P=0.01). The discardment rate
      of potential renal allografts increased slightly with 1.9% being discarded based
      on the biopsy result and 3.8% being discarded for other reasons. Under the biopsy
      protocol, 28/40 (70%) of donors with renal allograft biopsies had <20%
      glomerulosclerosis. The incidence of both delayed graft function and non-function
      was higher (P=0.014 and P=0.033, respectively) for the protocol biopsied
      allografts compared with the other non-biopsied allografts. One-year renal
      allograft survival was not significantly different between the protocol biopsied
      allografts versus the other non-biopsied allografts. CONCLUSIONS: A biopsy
      protocol for marginal potential renal allografts leads to acceptable allograft
      outcomes without significantly increasing allograft discardment.

PMID- 16109092
TI  - Adult onset tubulointerstitial nephritis and uveitis syndrome.
AB  - A Turkish woman aged 44 years who presented with a 1 month history of abdominal
      pain, fatigue and weight loss of 10 kg was diagnosed as having acute
      tubulointerstitial nephritis. Opthalmological evaluation revealed unilateral
      uveitis and contralateral chorioretinal scarring. X-ray films of the pelvis
      revealed unilateral sacroileitis. An elevated erythrocyte sedimentation rate, C
      reactive protein, tubular proteinuria and renal glucosuria returned to normal 2
      weeks after treatment was started. It is important to be aware of
      tubulointerstitial nephritis and uveitis syndrome in order to achieve a quick
      diagnosis in patients with renal impairment and tubular dysfunction with minor
      symptoms so that appropriate management can be started early.

PMID- 16109093
TI  - Acute pancreatitis associated with haemorrhagic fever with renal syndrome.

PMID- 16109094
TI  - Chronic pyonephrosis with polycystic change.

PMID- 16109095
TI  - Early allograft failure in an unrecognized case of primary hyperoxalosis.

PMID- 16109096
TI  - Level of blood creatinine in the recent reported cases of bird flu infection in
      Thailand and Vietnam.

PMID- 16109098
TI  - Characteristics of acetaminophen absorption in healthy unweaned calves as an
      indirect measurement of the oroduodenal transit rate of liquid meals.
AB  - Abomasal emptying plays an important role in the incidence of digestive problems
      in calves. Our aim was to evaluate the acetaminophen absorption test (APAT) for
      characterization of the oroduodenal transit (ODT) of liquid meals in unweaned
      calves. Six healthy, unweaned Simmental x Red Holstein crossbred calves were
      involved in the project. The study was performed in three blocks at 3, 6 and 9
      weeks of the calves' age. Within blocks, APAT was performed twice at an interval
      of at least 24 h. Once per each block, liquid transit was carried out with non
      coagulating electrolyte solution (NES). The second test within a block was
      performed either while atropine sulphate was administered (block I), or by
      feeding a coagulating milk replacer (block II), or by administration of NES by
      ruminal tube (block III). Data were compared within and among blocks. Significant
      differences of several APAT traits were present for the different types of
      feeding, the different types of meals, the administration of atropine sulphate
      and the different ages of the calves. The emptying index T(max)/C(max) was
      suggested to be a valuable kinetic parameter for the characterization of ODT in
      these calves. We conclude that APAT represents a valid technique for
      characterization of ODT of liquid meals in healthy unweaned calves and may be a
      valuable tool for the evaluation of the reticular groove mechanism, the abomasal
      emptying and the absorption capacity of the duodenum.

PMID- 16109097
TI  - Short-term effects on pro-inflammatory cytokine, lactoferrin and CD14 mRNA
      expression levels in bovine immunoseparated milk and blood cells treated by LPS.
AB  - Leucocytes (WBC) are recruited from peripheral blood into milk as part of the
      inflammatory response, mediated through cytokines or interleukins (IL)
      synthesized by mammary tissue and the milk somatic cells (SC). The inflammatory
      response is related to the concentration of SC and the cytokines produced. To
      investigate and to compare the kinetics of cytokine production in SC and WBC
      during inflammation, cell culture models were established, where SC and WBC were
      cultured in parallel (n = 3). In addition, macrophages or monocytes were isolated
      from milk and blood with antibody-coated magnetic beads and cultivated
      separately. Isolated cells were pure, unaltered and viable. Cultures were
      activated with 10 microg/ml lipopolysaccharide (LPS). After 0, 1, 2, 3, 4 and 8 h
      cells were harvested for RNA isolation. Cytokine [tumour necrosis factor alpha
      (TNFalpha), IL-1beta, IL-6] mRNA expression responses and transcriptional
      activity of CD14 and lactoferrin (LF) were quantified via a one-step real-time RT
      PCR. Significant cytokine mRNA increases were found in all four cell culture
      types and genes, with peaks after 1 and 2 h (TNFalpha > IL-6 > IL-1beta). In WBC
      or monocytes higher LPS responses and longer persistence could be found than in
      corresponding milk cells (IL-1beta > IL-6 > TNFalpha). SC and macrophages are
      less responsive to LPS stimulation than WBC or monocytes. The strength of the
      immune response in the blood system is much more prominent than in the mammary
      gland. This may be ascribed to the role of CD14 on the cytokine production of the
      investigated cells, or may be caused by the blood-to-milk diapedesis. The
      constitutive transcription of CD14 mRNA in WBC and monocytes was found to be 6 to
      15 times higher than in adequate milk cells.

PMID- 16109099
TI  - Extracellular matrix composition of the equine superficial digital flexor tendon:
      relationship with age and anatomical site.
AB  - The objectives of the present study were to test the hypotheses that: (1) the
      composition of the extracellular matrix of the equine superficial digital flexor
      tendon (SDFT) shows great functional similarities with articular cartilage, i.e.
      that significant differences exist in biochemical composition of differently
      loaded areas (which in the case of tendons may be more apparent as tendon shows
      more obvious differences than cartilage); and (2) that, as in articular
      cartilage, no substantial alterations in biochemical composition take place
      during ageing once adulthood has been attained. Tendon samples were taken from 60
      adult slaughter horses from a central area at cross-section in the mid-metacarpal
      region and at the height of the proximal sesamoid bones (sesamoid region) of the
      SDFT. Contents of collagenous and non-collagenous components were determined.
      None of the parameters were correlated with age in either region, except for a
      significant increase in pentosidine cross-links with age in the sesamoid region.
      Between the two anatomical regions, there were significant differences in all
      variables, except for hydroxylysylpyridinoline cross-links. It was concluded that
      in the equine SDFT, similar to articular cartilage, most molecular parameters are
      not influenced by age in mature horses, indicating a low remodelling rate. Tendon
      composition is clearly different between regions, apparently reflecting different
      specific modes of biomechanical loading at the points sampled.

PMID- 16109100
TI  - Cytologic features of testicular tumours in dog.
AB  - In this paper, we report on our experience of cytology of fine needle biopsies
      performed on 92 dogs with testicular tumours during the period from 1998 to 2002.
      Cytological diagnosis was consistent with seminoma in 20 cases, sertolioma in 16
      cases, Leydig cell tumours in 50 cases and mastocytoma in one case. Five cases
      could not be diagnosed by cytology. Cytological observations were confirmed after
      surgery by histopathological examination in 87 cases. Cytology provided a
      sensitivity of 95% for seminoma, 88% for sertolioma and 96% for Leydig cell
      tumours. The specificity was 100% for all three tumour types. In our experience
      cytology of fine needle aspirations of testicular tumours is a very reliable
      technique.

PMID- 16109101
TI  - The normal electrocardiogram of the unanaesthetized competition "Spanish Pouler"
      pigeon (Columba livia gutturosa).
AB  - This investigation was carried out on 64 healthy adult competition pigeons
      (Spanish Poulers) to determine reference values of electrocardiographic
      parameters in standard lead II; a comparative study between males and females was
      also performed to find changes in the electrocardiographic patterns related to
      sex. P wave was positive and monophasic; PR segment depression was present in 64%
      of records; the QRS pattern obtained was in most cases of the rS type, followed
      by the QS configuration. ST slurring (absence of ST) was observed in 47% of
      records and the mean electrical axis was in all cases negative. Statistically
      significant differences related to sex were found for P-wave, R-wave and T-wave
      amplitudes, showing the males have greater amplitudes than females, associated
      with the increase of cardiac tissue mass. No sex-related differences were found
      in heart rate and mean electrical axis.

PMID- 16109102
TI  - Persistent truncus arteriosus in a 6-year-old cat.
AB  - Truncus arteriosus (TA) was diagnosed in a 6-year-old neutered female domestic
      short-haired cat by two-dimensional and M-mode echocardiography, colour flow
      imaging and spectral Doppler examinations. The lesion was characterized by a
      single large artery originating from the right ventricle. A single ascending
      aorta and a single pulmonary trunk arose from the common arterial trunk. The
      residual pulmonary trunk immediately split into left and right branches. The
      lesion was identified as a type I (TA). This case is of interest because it is
      the first reported echo-Doppler description of such a malformation in felines,
      and because of the age of the cat at the time of diagnosis.

PMID- 16109103
TI  - Pharmacokinetics, urinary and mammary excretion of ceftriaxone in lactating
      goats.
AB  - The pharmacokinetic properties of ceftriaxone were investigated in 10 goats
      following a single intravenous (i.v.) and intramuscular (i.m.) administration of
      20 mg kg(-1) body weight. After i.v. injection, ceftriaxone serum concentration
      time curves were characteristic of a two-compartment open model. The distribution
      and elimination half-lives (t(1/2alpha), t(1/2beta)) were 0.12 and 1.44 h
      respectively. Following i.m. injection, peak serum concentration (C(max)) of 23.6
      microg ml(-1) was attained at 0.70 h. The absorption and elimination half-lives
      (t(1/2ab), t(1/2el)) were 0.138 and 1.65 h respectively. The systemic
      bioavailability of the i.m. administration (F %) was 85%. Following i.v. and i.m.
      administration, the drug was excreted in high concentrations in urine for 24 h
      post-administration. The drug was detected at low concentrations in milk of
      lactating goats. A recommended dosage of 20 mg kg(-1) injected i.m. every 12 h
      could be expected to provide a therapeutic serum concentration exceeding the
      minimal inhibitory concentrations for different susceptible pathogens.

PMID- 16109104
TI  - Electromyographical, ultrasonographical and morphological modifications in
      semitendinous muscle after transposition as ventral perineal muscle flap.
AB  - The aim of this study was to evaluate modifications occurring in semitendinous
      muscle after transposition as a ventral perineal muscle flap using
      electromyography, ultrasonography, and morphological studies. Ten male crossbreed
      dogs of 3-4 year old were used. The left semitendinous muscle was cut close to
      the popliteus lymph node, rotated and sutured at the perineal region. The
      contralateral muscle was considered as control. Motor nerve conduction studies of
      both sciatic-tibial nerves, and electromyographic and ultrasonographic
      examinations of both semitendinous muscles were performed before surgery and 15,
      30, 60, and 90 days postoperatively. Semitendinous muscle samples were collected
      for morphological analysis 90 days after surgery. No alterations were observed in
      clinical gait examinations, or in goniometrical and electroneuromyographical
      studies in pelvic limbs after surgery. Electromyography demonstrated that the
      transposed muscle was able to contract, but atrophy was detected by
      ultrasonography and morphological analysis.

PMID- 16109105
TI  - A Clinico-pathological study on the effect of vincristine on transmissible
      venereal tumour in dogs.
AB  - Transmissible venereal tumour (TVT) is a coitally transmitted neoplasm of dogs
      and is common among sexually active dogs, where sexual behaviour is not under
      control. Several treatment options are available for the treatment of the tumour,
      with chemotherapy being the most commonly employed. In this study, we
      investigated the clinical and cytological changes after weekly vincristine
      sulphate administration in 38 cases of naturally occurring TVT. Tumours totally
      regressed in 31 dogs after two to seven doses (mean 3.54 +/- 1.01) of
      vincristine. One dog died after the fifth dose of vincristine, and in six dogs,
      an additional treatment with doxorubicin was needed. Masses were still present in
      four dogs and the histopathological examination revealed small nodules of
      granulation tissue in two dogs, while viable tumour cells were identified in the
      remaining two cases. No recurrences were observed in a follow-up period of 7-49
      months (mean 13.64 +/- 9.66); in one dog, granulation tissue was detected in the
      surgery site after 2 months. Treatment success could easily be followed by the
      cytological changes. In conclusion, vincristine was found to be effective
      chemotherapeutic agent.

PMID- 16109106
TI  - Early enteral nutrition in young dogs suffering from haemorrhagic
      gastroenteritis.
AB  - The purpose of this study was to investigate clinical and metabolic effects of
      combined parenteral and oral nutrition compared with parenteral nutrition in
      young dogs with haemorrhagic gastroenteritis in a prospective clinical study.
      Dogs with acute gastroenteritis received either parenteral nutrition (group PN, n
      = 9) or combined parenteral and early enteral nutrition (group EN, n = 10).
      Infusions were compounded from amino acids, lipids, glucose and
      electrolyte/glucose solutions [149 g/l glucose, 20 g/l triglycerides, 40 g/l
      amino acids and 4009 kJ metabolizable energy/l (957 kcal ME/l)], and supplemented
      with potassium, phosphate and trace elements. Group EN received additionally a
      hydrolysed diet (74 kJ/kg BW(0.75) on day 2 and 148 kJ/kg BW(0.75) on days 3 and
      4). Glucose, triglycerides, protein, albumin, fibrinogen, urea, creatinine,
      alkaline phosphatase, glutamate dehydrogenase and glutamate pyruvate transaminase
      were measured before and during the infusions, haematological traits only before
      the infusions. Statistics included two-factorial anova and subsequent t-test or
      Wilcoxon test (P < 0.05). All dogs of group EN survived compared with seven of
      nine patients in group PN. Most dogs in the EN group vomited within half an hour
      after introduction of oral feeding on day 2 but tolerance for food increased on
      days 3 and 4. The general health status and faecal and blood parameters of the
      surviving dogs were similar (P > 0.05) between the groups. In all dogs leucocytes
      increased during the treatment period, haematocrit and haemoglobin levels
      declined. Infusions increased blood glucose and triglycerides (P < 0.05);
      however, no adverse signs were observed. Early enteral nutrition was possible
      after a short period of adaptation, however, vomiting can be a severe problem.
      The evaluation of clinical benefits of early enteral nutrition in young dogs with
      haemorrhagic gastroenteritis requires further investigations.

PMID- 16109110
TI  - Acetaminophen, aspirin, and caffeine versus sumatriptan succinate in the early
      treatment of migraine: results from the ASSET trial.
AB  - OBJECTIVE: To address the need for a rigorous, direct comparison of prescription
      and over-the-counter (OTC) migraine drugs and to expand the database on early
      treatment of migraine. BACKGROUND: Most people who experience migraine use OTC
      medications to treat their symptoms, but no head-to-head clinical trials
      comparing these agents with prescription migraine therapies have been published.
      In addition, even though most migraineurs treat early in the attack, few studies
      have been conducted to reflect this treatment pattern. METHODS: We compared a
      combination of nonprescription migraine medication (acetaminophen 500 mg, aspirin
      500 mg, and caffeine 130 mg) with a prescription migraine product (50 mg
      sumatriptan) in a randomized, controlled clinical trial in which subjects treated
      at the first sign of a migraine attack. Subjects who reported vomiting during
      more than 20% of migraine episodes or who required bedrest during more than 50%
      of migraine episodes were excluded from the study. Of the 188 subjects
      randomized, 171 took study medication and were included in the analysis.
      CONCLUSION: The combination of acetaminophen, aspirin, and caffeine was
      significantly more effective (P > .05) than sumatriptan in the early treatment of
      migraine, as shown by superiority in summed pain intensity difference, pain
      relief, pain intensity difference, response, sustained response, relief of
      associated symptoms, use of rescue medication, disability relief, and global
      assessments of effectiveness. An additional, larger clinical trial is needed to
      confirm these results.

PMID- 16109111
TI  - Sumatriptan and naproxen sodium for the acute treatment of migraine.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of treatment with a
      combination of sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg
      administered concurrently in the acute treatment of migraine. BACKGROUND: The
      pathogenesis of migraine involves multiple peripheral and central neural
      mechanisms that individually have been successful targets for acute (abortive)
      and preventive treatment. This suggests that multi-mechanism therapy, which acts
      on multiple target sites, may confer improved efficacy and symptom relief for
      patients with migraine. DESIGN AND METHODS: This was a multicenter, randomized,
      double-blind, double-dummy, placebo-controlled, four-arm study. Participants (n =
      972) treated a single moderate or severe migraine attack with placebo, naproxen
      sodium 500 mg, sumatriptan 50 mg, or a combination of sumatriptan 50 mg and
      naproxen sodium 500 mg. In the latter two treatment arms, the sumatriptan tablets
      were encapsulated in order to achieve blinding of the study. RESULTS: In the
      sumatriptan plus naproxen sodium group, 46% of subjects achieved 24-hour pain
      relief response (primary endpoint), which was significantly more effective than
      sumatriptan alone (29%), naproxen sodium alone (25%), or placebo (17%) (P <
      .001). Two-hour headache response also significantly favored the sumatriptan 50
      mg plus naproxen sodium 500 mg therapy (65%) versus sumatriptan (49%), naproxen
      sodium (46%), or placebo (27%) (P < .001). A similar pattern of between-group
      differences was observed for 2-hour pain-free response and sustained pain-free
      response (P < .001). The incidence of headache recurrence up to 24 hours after
      treatment was lowest in the sumatriptan plus naproxen sodium group (29%) versus
      sumatriptan alone (41%; P = .048), versus naproxen sodium alone (47%; P= .0035),
      and versus placebo (38%; P= .08). The incidences of the associated symptoms of
      migraine were significantly lower at 2 hours following sumatriptan 50 mg plus
      naproxen sodium 500 mg treatment versus placebo (P < .001). The frequencies and
      types of adverse events reported did not differ between treatment groups, with
      dizziness and somnolence being the most common. CONCLUSIONS: This is among the
      first prospective studies to demonstrate that multi-mechanism acute therapy for
      migraine, combining a triptan and an analgesic, is well tolerated and offers
      improved clinical benefits over monotherapy with these selected standard
      antimigraine treatments. Specifically, sumatriptan 50 mg (encapsulated) and
      naproxen sodium 500 mg resulted in significantly superior pain relief as compared
      to monotherapy with either sumatriptan 50 mg (encapsulated) or naproxen sodium
      500 mg for the acute treatment of migraine. Because encapsulation of the
      sumatriptan for blinding purposes may have altered its pharmacokinetic profile
      and thereby decreased the efficacy responses, additional studies are warranted
      that do not involve encapsulation of the active treatments and assess the true
      onset of action of multi-mechanism therapy in migraine. This study did show that
      the combination of sumatriptan and naproxen sodium was well tolerated and that
      there was no significant increase in the incidence of adverse events compared to
      monotherapy.

PMID- 16109112
TI  - Pain thresholds in daily transformed migraine versus episodic migraine headache
      patients.
AB  - OBJECTIVE: The objective of this study was to test whether pain thresholds of
      patients with episodic migraine (EM) are significantly different from transformed
      migraine (TM) patients as measured by Quantitative Sensory Testing (QST) and
      Semmes-Weinstein Monofilaments (SW). BACKGROUND: Although there are many
      theories, none have undeniably proven why many TM patients are refractory to
      triptans and other gold standard medications. The hypothesis was that baseline
      pain thresholds of TM patients are lower than EM patients. METHODS: Episodic (n =
      40) and Transformed (n = 41) migraineurs with and without aura were examined with
      QST and SW over eight locations (bilateral ophthalmic, maxillary, C4/posterior
      neck, and forearm). All patients completed two visits, baseline and severe
      migraine. RESULTS: TM patients have lower pain thresholds, than EM patients, as
      measured on QST and SW testing. A total of 81 out of 129 patients completed both
      parts of the study at baseline and severe migraine. There were significant
      differences (P < .05) between EM and TM groups at baseline on maxillary, neck (EM
      = 45.91 degrees C and TM = 42.94 degrees C), and arm. CONCLUSIONS: TM patients,
      clinically known to report skin hypersensitivity during migraine, were found to
      have lower pain thresholds than EM patients, both with severe migraine, and at
      baseline, measured by QST and SW mechanical testing. As with Burstein's work in
      EM patients with lowered pain thresholds during their acute migraine, central
      sensitization may be the explanation for non-responsiveness to triptans in a high
      proportion of TM patients. The difference in pain threshold at the neck location
      was such a strikingly frequent difference between EM and TM patients, that this
      indicates the need for future research to clarify the directional relationship
      and the relative importance of muscular versus peripheral versus central
      hypersensitivity in the determination of allodynia.

PMID- 16109113
TI  - Brush allodynia in hospitalized headache patients.
AB  - OBJECTIVE: To describe the incidence and time course of dynamic mechanical
      allodynia (brush allodynia, BA) in an inpatient headache population. BACKGROUND:
      Four types of cutaneous allodynia (heat, cold, static mechanical [pressure], and
      dynamic mechanical [brush] allodynia) can be studied in headache patients. In
      episodic migraineurs, the development of cutaneous allodynia heralds a change in
      treatment response. However, little is known about the functional significance of
      BA, and little is known about the frequency of any type of cutaneous allodynia
      among patients with chronic or more severe headache disorders. Methods.-The
      protocol was approved by the institutional review board of our university
      hospital. A total of 78 subjects were tested for allodynia on days 1, 3, and 5 of
      an inpatient hospital stay using a 4 x 4 folded gauze pad stroked 10 times at
      three bilateral sites (forehead, jaw, and forearm). Subjects were queried about
      the signs and symptoms of their headaches. Headache intensity was graded with a
      verbal 11-point scale and the intensity of allodynia was graded using a 10 cm
      visual analog scale. RESULTS: A total of 61 patients had transformed migraine
      (TM). BA was present at some point during the hospitalization in 32 subjects
      (41%). Neither age nor duration of daily headache correlated with headache
      severity. Headache intensity, a history of sensory symptoms or weakness, and
      subjective blurred vision accompanying the headache correlated with the presence
      of BA (P< or = .05). Unilateral headaches were more likely to be associated with
      BA (P = .01), independent of headache severity. When headache was unilateral, BA
      was greatest ipsilateral to the headache. BA did not influence outcome as
      measured by length of stay or the likelihood of being discharged headache-free.
      The rate of decline of headache intensity and allodynia score were similar.
      CONCLUSION: BA is common in hospitalized headache patients. Subjects with more
      severe unilateral headaches were more likely to have BA. The presence of BA did
      not predict treatment failure in an inpatient setting.

PMID- 16109114
TI  - Efficacy of the 5-HT1A agonist, buspirone hydrochloride, in migraineurs with
      anxiety: a randomized, prospective, parallel group, double-blind, placebo
      controlled study.
AB  - OBJECTIVE: To examine the efficacy of buspirone, a 5-HT1A agonist, for migraine
      combined with anxiety disorder. BACKGROUND: Modulation of the 5-hydroxytryptamine
      (5-HT) system is used for the neuropharmacology of migraine treatment; however,
      the involvement of the 5-HT1A system in migraine is not fully understood.
      METHODS: Seventy-four outpatients aged 20 to 70 years (mean, 46.4; SD, 12.8) were
      analyzed. All subjects were diagnosed to have migraine according to the
      International Headache Society criteria and anxiety disorder according to DSM-IV.
      Subjects were randomly assigned to treatment with either buspirone (10 mg/day) or
      placebo for 6 weeks. Efficacy variables included changes in headache frequency,
      headache intensity, Hamilton Anxiety Rating Scale (HAM-A), Headache Self-Efficacy
      Scale (HMSE), and Headache Disability Inventory (HDI). The correlation between
      the headache improvement and the anxiolytic effect was analyzed. RESULTS:
      Headache frequency showed a 43.3% reduction in the buspirone-treated group, but
      by only 10.3% in the placebo group. HAM-A and HDI were also significantly more
      lowered in buspirone-treated patients than in placebo-treated patients. However,
      headache intensity and HMSE score were unchanged. Correlation analysis of the
      relation between headache frequency reduction and HAM-A improvement, revealed no
      significant association. CONCLUSIONS: In this study, buspirone showed a
      prophylactic effect in migraine with anxiety disorder, which was not secondary to
      its anxiolytic effect. This suggests that the agonistic action for 5-HT1A can be
      directly effective in migraine prophylaxis. However, more long-term study is
      warranted before concluding the efficacy.

PMID- 16109115
TI  - Cost-effectiveness of topiramate in migraine prevention: results from a
      pharmacoeconomic model of topiramate treatment.
AB  - OBJECTIVE: Patients whose migraines are frequent, cause disruptions of daily
      routines, or are unresponsive to acute treatment are primary candidates for
      preventive migraine therapy. This cost-effectiveness model assesses the clinical
      and economic impact of topiramate (TPM) therapy versus no preventive treatment
      for migraine headache in the United States. BACKGROUND: Despite significant
      progress in treatment options, the economic burden of migraine to patients,
      employers, health systems, and society is substantial. Treatment strategies for
      migraine are directed toward managing acute episodes. However, preventive therapy
      should be used for patients with frequent migraine attacks (>2 per month) or
      those experiencing attacks that disrupt daily routines. METHODS: Data for the
      model were obtained from the published literature and pooled results of two
      randomized, double-blinded, placebo-controlled trials of TPM in migraine
      prevention. Model inputs included baseline migraine frequency (the base case
      assumed 6 per month, consistent with the average rate in the TPM trials),
      treatment discontinuation (including discontinuation due to adverse events),
      treatment response (ie, > or = 75%, 50% to 75%, and <50% reduction in migraine
      frequency), cost of preventive therapy (TPM plus physician visits for medication
      titration), cost of acute treatment per attack (including pharmacy and medical
      service costs), hours of disability per attack, hourly wage, and quality-of-life
      (utility) weights. Model outcomes included the number of migraines averted,
      disability hours, total cost of acute and preventive treatment, and lost wages.
      Results were expressed as cost per migraine averted and cost per quality-adjusted
      life years (QALY). All costs were stated as 2002 U.S. dollars. We also conducted
      sensitivity analyses to assess the robustness of model findings with respect to
      variation in key parameters. RESULTS: We estimated that the use of TPM would
      prevent 1.85 migraines per patient and almost 5 hours of disability per month
      versus no preventive treatment. Resulting savings in cost of acute treatment
      (dollar 27) and work loss (dollar 51) offset 68% of the expected monthly cost of
      TPM (dollar 113). The incremental cost per migraine averted was dollar 19, while
      the incremental cost per QALY was estimated to be dollar 10,888 (dollar 26,191
      when indirect costs were excluded from the analysis). Model results were
      sensitive to baseline migraine rate and gain in health utility from migraine
      prevention. CONCLUSIONS: Economic savings associated with reduced migraine
      frequency offset approximately two thirds of the cost of preventive TPM therapy.
      The cost-effectiveness of TPM depends on utility gains associated with a reduced
      frequency of migraine headaches, which is the subject of ongoing research.
      However, results from our model suggest that the use of TPM in prevention of
      migraine may offer reasonable value for money relative to many well-accepted
      medical interventions.

PMID- 16109116
TI  - Topiramate improves health-related quality of life when used to prevent migraine.
AB  - OBJECTIVE: To assess changes in health-related quality of life (HRQoL) measures
      among patients receiving topiramate (TPM) 100 mg/d in two divided doses for
      migraine prevention in three randomized, double-blind, placebo-controlled, 26
      week trials with similar protocols and study populations. BACKGROUND: Migraine
      substantially impairs HRQoL and work productivity before, during, and after
      attacks. Approximately 50% of patients with migraine could be recommended for
      preventive therapies, yet only 3% to 5% of patients receive them. TPM is an
      effective and generally well-tolerated migraine prophylactic (preventive) therapy
      for adults, as demonstrated in several randomized, double-blind, placebo
      controlled trials. The most common adverse events in double-blind, placebo
      controlled studies of TPM in migraine prevention are paresthesia, fatigue,
      anorexia, nausea, taste alteration, and diarrhea. DESIGN AND METHODS: The
      Migraine-Specific Questionnaire (MSQ, version 2.1) was used to assess the effect
      of TPM 100 mg/d on the functionality and HRQoL of randomized intent-to-treat
      (ITT) and study-completer populations pooled from three randomized, double-blind,
      placebo-controlled trials. MSQ scores (0 to 100, higher score indicates better
      functioning) were assessed for the following three domains: role restriction
      (examines the degree to which performance of daily activities is limited by
      migraine), role prevention (examines the degree to which performance of daily
      activities is interrupted by migraine), and emotional function (examines feelings
      of frustration and helplessness due to migraine). Between-group differences from
      baseline in mean MSQ domain scores for TPM 100 mg/d and placebo were compared
      using a mixed-effects model with piecewise linear regression. Effect sizes were
      calculated to estimate the magnitude of change in HRQoL that can be associated
      with TPM therapy. RESULTS: TPM 100 mg/d significantly improved all three MSQ
      domains compared with placebo for both the ITT (TPM, n = 372; placebo, n = 362)
      and study-completer (TPM, n = 220; placebo, n = 216) populations (P < .001 for
      all three domains, both populations). Effect sizes for TPM 100 mg/d varied from
      0.40 to 0.78, indicating that the changes in MSQ scores for TPM 100 mg/d were
      moderate and may be clinically significant. CONCLUSION: TPM 100 mg/d has been
      shown to be effective in the prevention of migraine headache in adults. As the
      MSQ results from the three randomized, placebo-controlled trials indicate, HRQoL
      is significantly improved for up to 6 months following initiation of treatment.

PMID- 16109117
TI  - Effect of divalproex on metabolic parameters is dose related in migraine
      prophylaxis.
AB  - OBJECTIVE: To examine the metabolic effects of three divalproex dosing regimens
      in patients with migraine. BACKGROUND: Epidemiological and clinical studies have
      demonstrated a strong association between serum lipid levels and the development
      of coronary artery disease. Thus, it is important to understand the impact of
      chronically administered medications on serum lipids. Metabolic properties of
      divalproex, an approved and commonly used treatment for migraine prophylaxis,
      have not been systematically studied in patients with migraine. METHODS: Adult
      patients with migraine were randomized to receive one of three daily doses of
      divalproex (500 mg [n = 45], 1000 mg [n = 43], or 1500 mg [n = 44]) or placebo (n
      = 44) for 12 weeks. Post hoc analyses were performed to determine the effects of
      divalproex on total cholesterol, glucose, weight, and body mass index (BMI).
      RESULTS: The treatment groups were similar at baseline based on demographic and
      clinical characteristics and the use of concomitant medications. Divalproex
      resulted in a dose-related mean decrease from baseline in total cholesterol: -5.7
      mg/dL or 3% reduction with 500 mg/day; -8.4 mg/dL or 4% reduction with 1000
      mg/day; and -12.8 mg/dL or 7% reduction with 1500 mg/day (P < .05 for 1500 mg/day
      vs. placebo). There were no differences between any divalproex dose group and
      placebo for mean change from baseline in glucose, weight, or BMI. CONCLUSIONS:
      Divalproex results in a dose-dependent reduction in serum cholesterol within the
      first 3 months of therapy, with no significant change in serum glucose or BMI.

PMID- 16109118
TI  - Migraine pain location: a tertiary care study of 1283 migraineurs.
AB  - OBJECTIVES: This study of headache location in migraine was performed (1) to
      document the location of pain in a large group of migraine patients and (2) to
      assess the impact of different types of migraine, gender, aura, and headache
      features on the location of the headache. BACKGROUND: The literature documenting
      the location of the pain of acute attack of migraine is sparse. METHODS: A total
      of 1283 migraine patients (ICHD, 2004, 1.1, 1.2, 1.5.1, and 1.6) were evaluated
      at the 1st visit. Headache location and character were graded on a scale of 0 to
      3 with 0 being none and 3 the most. Triggers were graded on a frequency scale of
      0 to 3; 0 = none; 1 = less than 1/3 of time; 2 = between 1/3 and 2/3 of time; 3 =
      greater than 2/3 of time. Other headache features and medication responsiveness,
      were also recorded. Patients were stratified by migraine type and headache
      frequency. Combined and isolated locations, and the impact of age, gender,
      headache frequency, migraine types, and aura were addressed. Unremitting headache
      was excluded. RESULTS: Migraine patients reported that the highest location
      frequencies were in the eyes (67.1%), temporal (58.0%), and frontal (55.9%). The
      lowest were diffusely (17.5%) and vertex (24.1%). The intermediate were in the
      occipital (39.8%) and neck areas (39.7%). Other migraine types were remarkably
      similar. Hemi-cranial location was present in 66.6% of patients, 71.2% in
      episodic migraine and 61.4% in chronic migraine, 67.2% in females and 63.2% in
      males, 59.7% in migraine without aura and 68.9% in migraine with aura 100% of the
      time. Headaches were reported on the right side in 27.3%, left side 24.3%, both
      sides 23.7%, either side 15.0%, and in the middle of the head in 4.6% of cases.
      Significant differences in headache location were seen only within migraine and
      not other migraine types. Headache location was not correlated with lifetime
      duration of migraine, prodrome, response to triptan, intensity, time to peak of
      headache, recurrence frequency, and time to recurrence. CONCLUSIONS: This study
      provides a detailed documentation of headache location in a large cohort of
      patients. The commonest locations are the orbital, frontal, and temporal areas
      and least common sites being diffuse and the vertex. A single location is
      infrequent. Hemi-cranial location is present in two thirds of subjects and a
      quarter each are on the left side, right side, and both sides. The locations of
      the headache are very similar in different migraine types, but there are some
      differences. Under age 21 and older patients tended to show some differences in
      location and side. Location differences are seen with gender, headache frequency,
      and aura. Location shows many correlations with triggers and headache features.

PMID- 16109119
TI  - Burden of illness and satisfaction with care among patients with headache seen in
      a primary care setting.
AB  - OBJECTIVE: To assess the current level of headache burden and the headache
      management needs at three diverse clinical sites. BACKGROUND: Headache is a
      common disabling disorder that is costly for the patient and a management
      challenge for physicians. The determination of whether and how to intervene to
      improve headache management depends on both the burden of disease and the
      characteristics of patients that would likely be targeted. METHODS: Patients from
      three healthcare organizations were identified by administrative records as
      having either migraine or tension-type headache and then mailed a survey that
      addressed demographics, headache type, headache-related disability, depression
      and anxiety, satisfaction with care, general health, worry about headache,
      problems with headache management, and healthcare utilization. Comparisons were
      made across sites and between patients with more and less severe headache-related
      impairments. RESULTS: Of the 789 patients contacted, 385 (50%) returned a survey.
      While the socio-demographic characteristics of the patients were diverse,
      headache-related characteristics were similar. These patients have significant
      problems with headache management, disability, pain, worry, and dissatisfaction
      with care. Patients who described higher headache-related impairment experienced
      significantly greater problems in these areas, perceived themselves to be in
      worse general health, and had significantly greater use of medical services than
      those with lower headache severity. CONCLUSIONS: Despite various elements of
      heterogeneity, we observed across the sites a consistent need for improvement in
      headache management. Future efforts should be directed at developing and
      evaluating methods for effectively improving headache management.

PMID- 16109120
TI  - Serotonin transporter gene polymorphism and migraine in the Korean population.
AB  - OBJECTIVE: To evaluate the association between a serotonin (5-HT) transporter
      gene polymorphism and migraines in Koreans. BACKGROUND: The 5-HT metabolism is
      believed to play an important part in the pathophysiology of migraines, and a
      polymorphism of the serotonin transporter (5-HTT) promoter region might influence
      5-HTT expression and serotonin uptake. METHODS: This study compared 52 patients
      with migraine and 170 healthy control subjects in order to determine the
      association between a polymorphism of the 5-HTT gene-linked polymorphic region (5
      HTTLPR) and migraine. Using PCR techniques, the products of the 484-base pair
      (bp) fragments were denoted as being short alleles (s) and those of 528 bp as
      being long (l). RESULTS: The genotype distribution of the healthy controls was
      s/s (56.5%), s/l (38.2%), and l/l (5.3%) and that of the patients with migraine
      was 65.4%, 30.8%, and 3.8%, respectively. No significant differences were noted
      in the genotype and allele frequencies of 5-HTTLPR between the patients with
      migraine and the control subjects. CONCLUSIONS: A 5-HTTLPR polymorphism does not
      appear to be involved in the genetic predisposition to migraines.

PMID- 16109121
TI  - Enhanced trigemino-cervical-spinal reflex recovery cycle in pain-free
      migraineurs.
AB  - OBJECTIVE: To evaluate trigemino-cervical-spinal reflexes (TCSRs) in a group of
      migraine patients during the pain-free period. BACKGROUND: TCRSs are part of a
      complex nocifensive response involving the cervical and the upper limb muscles,
      and are modulated by supraspinal inhibitory pathways; it may, thus, be possible
      to use TCRSs to explore the trigeminal system in migraineurs. METHODS: A total of
      43 migraine patients without aura (MWoA, 32 patients) or with typical aura (MWA,
      11 patients) and 30 age- and sex-matched healthy subjects took part in the study.
      TCRSs were obtained by stimulating the supraorbital nerve and recorded from the
      semispinalis capitis muscle and the biceps brachii. The latency (L, msec), area
      (A, mVms) and recovery cycle of the reflexes were recorded. The effects of
      heterotopic painful stimulation on the neurophysiological parameters were studied
      by a validated cold pressor test (CPT). RESULTS: No significant changes were
      found between either migraine patients and controls or MWoA and MWA patients in
      the mean values in the L and A of TCRSs (t-test, P > .05). The recovery curve of
      the trigemino-cervical reflexes (TCRs) was significantly faster in migraine
      patients than in controls, while no differences were found in the trigemino
      spinal reflexes (TSRs) (t-test, P < .01). Activation of the diffuse inhibitory
      controls through the CPT induced a significant reduction in the TCRs and TSRs
      area in both migraine patients and controls (paired t-test, P < .01), though the
      extent of this reduction did not differ significantly between migraineurs and
      controls (t-test, P > .05). COMMENTS: Our data suggest that the pain-free period
      in migraine patients is characterized by a hyperexcitability of the trigeminal
      pathways and of their anatomical and functional connections with the upper
      cervical cord neurons, and that this abnormal hyperexcitability does not appear
      to be due to a lack of a supraspinal inhibitory modulation.

PMID- 16109122
TI  - Treatment of cluster headache attacks with less than 6 mg subcutaneous
      sumatriptan.
AB  - BACKGROUND: Subcutaneous (SQ) sumatriptan 6 mg is effective in the treatment of
      acute cluster headache attacks. However, patients sometimes benefit from a dose
      less than 6 mg. OBJECTIVE: Therefore, we designed a prospective open study to
      evaluate how many patients benefit from a dose less than 6 mg SQ sumatriptan.
      METHODS: We enrolled 81 consecutive patients with cluster headache and recorded
      their use of SQ sumatriptan and oxygen. Patients regularly using SQ sumatriptan 6
      mg were advised to treat attacks with doses less than 6 mg and with oxygen.
      Efficacy and side effects of the different treatment options (6 mg, 3 mg, 2 mg,
      and oxygen) were evaluated. RESULTS: As a result, 74% of the patients using SQ
      sumatriptan 3 mg showed efficacy and 89% reported efficacy after 2 mg. Seventy
      nine percent reported side effects after the use of SQ sumatriptan 6 mg (29%
      severe side effects). After the use of 2 mg SQ sumatriptan, only 50% of the
      patients reported side effects, none of these were classified as severe.
      Patients' preference was 41% for 6 mg sumatriptan, 28% for doses less than 6 mg,
      and 31% for oxygen. CONCLUSIONS: We conclude that sumatriptan in doses less than
      6 mg can be effective in the acute treatment of cluster headache attacks. We
      suggest that patients should have experience in their individual efficacy of
      sumatriptan doses less than 6 mg.

PMID- 16109123
TI  - A pilot study of botulinum toxin A for headache in cervical dystonia.
AB  - OBJECTIVE: To evaluate the prevalence of associated headache (HA) pain with
      craniocervical dystonia and the therapeutic effect of BoNT-A injections on the HA
      component when injected for cervical dystonia. BACKGROUND: HA associated with
      craniocervical dystonia is a recent formally codified entity, but has not been
      systematically studied. METHODS: We identified 44 subjects from three movement
      disorder clinics who presented with craniocervical dystonia and concurrent HA
      pain. The subjects were injected with botulinum toxin type A (BoNT-A) and
      prospectively evaluated with the Toronto Western Spasmodic Torticollis Rating
      Scale (TWSTRS), headache diaries, Headache Impact Test (HIT-6), and Migraine
      Disability Assessment Scale (MIDAS), along with HA pain anatomy and adverse
      events, at baseline, and at 4, 8, and 12 weeks post-injection. RESULTS: As
      expected, all aspects of the TWSTRS robustly improved. Headache diaries and the
      HIT-6 also improved at 4, 8, and 12 weeks post-injection. Sections of the MIDAS
      improved, and adverse events were minimal. CONCLUSION: BoNT-A safely improves
      headache associated with craniocervical dystonia when administered for the
      primary condition of craniocervical dystonia.

PMID- 16109124
TI  - Images from headache. Sacular aneurysm involving the right middle cerebral artery
      trifurcation and a smaller aneurysm involving the intracranial right internal
      carotid in its cavernous portion.

PMID- 16109125
TI  - Burning mouth syndrome.

PMID- 16109126
TI  - Hemicrania continua responsive to verapamil.
AB  - Hemicrania continua (HC) is a rare headache syndrome, typically responsive to
      indomethacin, although patients resistant to this drug have been described. Few
      treatment alternatives have been proposed in the literature. We here report a
      patient with HC whose initial excellent response to indomethacin faded but then
      responded remarkably to verapamil.

PMID- 16109127
TI  - Tinnitus in migraine: an allodynic symptom secondary to abnormal cortical
      functioning?
AB  - Tinnitus is not a common auditory symptom in migraine. Recent research suggests
      that central sensitization (CS) develops in most migraneurs during the course of
      a migraine attack. Herein we describe 3 patients with primary headache disorders
      and tinnitus as their chief complaint, in whom the tinnitus intensity
      consistently increased during headache attacks. In headache patients, tinnitus
      may be related to spontaneous and aberrant neural activity at any level along the
      auditory axis, with abnormal reorganization processes in the auditory cortex
      following hearing receptor damage. We hypothesize that the tinnitus intensity
      increase could be an allodynic symptom related to CS, or alternatively could be
      associated with cortical hyperexcitability.

PMID- 16109128
TI  - Classifying migraine patients, not migraine headaches.

PMID- 16109129
TI  - Change in frequency pattern in cluster headache induced by subcutaneous
      sumatriptan.

PMID- 16109130
TI  - Clinical trial ethics.

PMID- 16109131
TI  - Supplementary comment on case: transient visual loss, lower extremity
      monoparesis, and sudden sharp headaches precipitated by long car trips.

PMID- 16109135
TI  - Parathyroid interventions for secondary hyperparathyroidism in hemodialyzed
      patients.
AB  - Although parathyroidectomy (PTX) is the ultimate treatment for secondary
      hyperparathyroidism (SHPT) that is resistant to medical treatment, recent
      advances in ultrasonographic techniques have increased the treatment options in
      Japan. Percutaneous ethanol injection therapy (PEIT) of the parathyroid was
      approved under the national health insurance system in 2004, and there have been
      trials of direct injection of vitamin D (VD) preparations. We followed 30
      patients for at least 1 year who had undergone PEIT at the same institution. The
      overall mean concentration of intact parathyroid hormone (PTH) fell from 865.3+/
      388.4 pg/mL to 291.9+/-277.8 pg/mL, or 34% of the pretreatment value. The effect
      was even more pronounced for one or two glands, with 68.4% reaching the target of
      intact PTH<or=300 pg/mL recommended in the K/DOQI guidelines, in comparison with
      36.4% of cases of hypertrophy of three or four glands. The average time taken to
      achieve the target PTH concentration was 4 months. No correlation was found
      between the response to PEIT and the total parathyroid volume, or the volume of
      glands with suspected nodular hyperplasia. Cases in which PTH does not fall
      sufficiently after five or more injections should be considered refractory to
      PEIT and evaluated for PTX. Following PEIT, PTH falls relatively slowly, whereas
      after total PTX with forearm autograft the PTH concentration falls immediately
      and may still be less than 60 pg/mL 4 or 5 years later. Bone biopsies performed 1
      year after total PTX with autograft showed a change from an osteitis fibrosa
      pattern to an adynamic bone disease pattern. In some cases of hypertrophy of
      three to four glands, markers of bone metabolism kept decreasing more than did
      PTH, corresponding to marked improvement in the patients' quality of life.
      Important considerations for treatment selection include: (i) ultrasonography of
      the cervical region as screening; (ii) earlier recognition of the limits of
      medical therapy; and (iii) the number of affected glands, the age of the patient,
      and the likely course postintervention.

PMID- 16109136
TI  - Management of calcium, phosphorus and bone metabolism in dialysis patients using
      sevelamer hydrochloride and vitamin D therapy.
AB  - Abnormalities of mineral metabolism, including those of calcium (Ca), phosphorus
      (P), and parathyroid hormone (PTH) in patients on maintenance hemodialysis induce
      severe bone involvement, which manifests as renal osteodystrophy. Recently,
      vascular calcification caused by abnormal mineral metabolism has been attracting
      attention because cardiovascular diseases (CVD) are a major cause of death in
      hemodialysis patients. Since 2000, the treatment standard for overt secondary
      hyperparathyroidism (SHPT) in our facilities has shifted from conventional or
      pulse therapy with oral vitamin D3 (VitD) to intravenous pulse therapy with
      maxacalcitriol or calcitriol. After selecting the criterion of overt SHPT as
      intact-PTH>500 pg/mL, the proportion of overt SHPT cases among all hemodialysis
      patients decreased from 12% at the start of intravenous pulse treatment to 6.4%
      after 4 years' treatment. However, the number of patients who had an interruption
      to pulse treatment because of hypercalcemia and/or hyperphosphatemia was high and
      it became a bottleneck for the continuation of the therapy. The major cause of
      hypercalcemia is considered to be Ca load derived from oral calcium carbonate. In
      Japan, sevelamer hydrochrolide (SH), which does not contain Ca, has been
      available commercially since 2003 and potentially should enable a reduction in
      the incidence of overt SHPT during long-term intravenous treatment when combined
      with careful adjustment of the dose of VitD and strict monitoring of Ca and P
      level concentrations. In this study, we found that the proportion of patients who
      satisfy the recommended serum concentrations of Ca and P reported by K/DOQI
      guideline was low irrespective of the serum concentration of intact-PTH. The
      aortic calcification index was high in the patient group with lower intact-PTH
      level concentration, probably because of reduced Ca and P buffering ability
      associated with reduced bone turnover. We consider that VitD treatment with SH
      might give better control of the intact-PTH level concentration within the range
      recommended by the K/DOQI guideline.

PMID- 16109137
TI  - Introduction to sevelamer hydrochloride and its clinical effects.
AB  - Sevelamer hydrochloride (SH) is widely used for the treatment of
      hyperphosphatemia in patients with renal failure who are on maintenance
      hemodialysis. In this study, we investigated the clinical effects of SH,
      administered as either monotherapy or combined with a calcium carbonate
      formulation, on the metabolism of calcium (Ca) and phosphorus (P) in patients who
      had been taking a Ca-based binder. Patients were divided into three groups (i):
      switched completely from a Ca-based binder to SH (complete switch); (ii) dosage
      of the Ca-based binder was reduced, and SH introduced (partial switch); and (iii)
      dosage of the Ca-based binder was not reduced and SH introduced (combination
      therapy). We also examined the effects of the introduction of SH on the lipid
      profile and parathyroid hormone (PTH) concentration. Comparison between groups of
      the numbers of successfully treated cases (reaching target concentrations of
      serum P=5.5 mg/dL and Ca x P product=55 mg2/dL2 within 6 months of treatment)
      showed that the likelihood of reaching target levels was higher if Ca-based
      binder was maintained as much as possible (combination therapy>partial
      changeover>complete changeover). Furthermore, treatment with SH decreased total
      cholesterol and non-HDL cholesterol concentrations significantly, and also
      increased HDL cholesterol and PTH concentrations compared to pre-treatment. These
      results suggest that when a calcium carbonate formulation is already in use, as
      far as compliance allows, the dosage should not be reduced when SH is added.
      Despite its beneficial effects on the lipid and PTH concentrations, preventing an
      excessive increase in the PTH concentration is essential when using SH.

PMID- 16109138
TI  - Role of sevelamer hydrochloride in the coronary artery calcification score.
AB  - The coronary artery calcification score (CACS) is higher in hemodialysis (HD)
      patients than in non-HD patients for each age group from the fifth to the eighth
      decade of life. In order to clarify the relationship between the rate of change
      in the CACS and several factors related to calcium (Ca) and phosphate (P)
      metabolism in HD patients, we determined the CACS twice in 144 HD outpatients at
      an interval of approximately 12 months (2003 and 2004). The dosage of vitamin D
      formulations (alfacalcidol or maxacalcitol) was reduced or ceased if the serum Ca
      concentration exceeded 5.0 mEq/L, or the serum P concentration exceeded 6.0
      mg/dL, and the dosage of combined sevelamer hydrochloride (SH) and calcium
      carbonate (CaCO3), as the phosphate binder, was adjusted to maintain the
      concentrations below these levels. The study parameters were: (1) the total
      dosage of alfacalcidol (microg), maxacalcitol (microg), SH (mg), and CaCO3 at the
      time of each CACS measurement; and (2) serum concentrations of Ca, P, alkaline
      phosphatase, high-sensitivity parathyroid hormone (HS-PTH), total protein,
      albumin, total cholesterol, triglycerides (TG). Regression analysis showed a
      significant correlation among the total SH dosage, TG, and alphaCACS. Future
      investigations will include the differences in alphaCACS between patients treated
      with SH who experience a rise in Ca and/or P and those with a decrease in Ca
      and/or P.

PMID- 16109139
TI  - Parathyroid cell growth in patients with advanced secondary hyperparathyroidism:
      vitamin D receptor, calcium sensing receptor, and cell cycle regulating factors.
AB  - The parathyroid gland (PTG) is a unique endocrine organ in which the quiescent
      glandular cells begin to proliferate in response to the demand for maintaining
      calcium (Ca) homeostasis in the progressive course of renal failure, leading to
      secondary hypereparathyroidism (SHPT). SHPT is characterized with continuous over
      secretion of parathyroid hormone (PTH) and high turn-over bone disease, osteitis
      fibrosa, and the major factors include a deficiency of active vitamin D,
      hypocalcemia, and phosphate retention. With long-term end-stage renal failure,
      SHPT becomes resistant to conventional medical treatment such as phosphate
      binders and active vitamin D supplementation, and the growth of the PTG
      accelerates with the pattern of hyperplasia changing from diffuse to nodular
      type. In this process, the sigmoid curve between extracellular Ca concentration
      (exCa) and the plasma level of PTH shifts to the upper-rightward, indicating both
      an absolute increase in PTH secretion and the resistance of PT cells to exCa.
      Many experimental and human studies have revealed down-regulation of vitamin D
      receptor (VDR), calcium-sensing receptor (CaSR), and retinoid X receptor (RXR) in
      PT cells. The sustained proliferation of PT cells after obtaining autonomicity is
      another characteristic feature of SHPT. In this context, it has been demonstrated
      that the cell cycle is markedly progressed, where the expression of cyclin
      dependent kinase inhibitor (CDKI), p21 and p27, is depressed in a VDR-dependent
      manner. These pathological features are most evident in nodular hyperplasia, in
      which monoclonal proliferation is obvious, indicating the phenotypic changes have
      occured in PT cells. It has been observed by Fukagawa and colleagues that
      pharmacologically high dose of active vitamin D administered orally can cause
      small-size PTG hyperplasia to regress in patients with advanced SHPT. Successful
      renal transplantation may also restore VDR and CaSR expressions in the diffuse
      type, in association with increasing TUNEL-positive cells. Thus, it is important
      to vigorously treat SHPT when the PT cell proliferation is in the reversible
      stage of diffuse hyperplasia.

PMID- 16109140
TI  - Management of secondary hyperparathyroidism.
AB  - Secondary hyperparathyroidism (SHPT) remains an inevitable consequence of
      untreated chronic uremia. It is the result of a combination of phosphate (P)
      retention, failure of calcitriol synthesis, and hypocalcemia. Therapies used to
      correct these abnormalities, namely active vitamin D replacement, calcium (Ca)
      supplementation, and phosphate (P) restriction, have moderate efficacy but are
      prone to unacceptable side-effects. However, there have been new developments in
      the control of P, vitamin D replacement and modulation of the Ca sensing receptor
      (CaSR) using calcimimetics. Sevelamer, and in the near future lanthanum, are
      offering a reasonable level of P control without the toxicities inherent with
      either aluminum- or Ca-based phosphate binders, and other phosphate binders are
      in development. 'Non calcemic' vitamin D metabolites include 22-oxacalcitriol,
      paricalcitol, and doxercalciferol. In various experimental models 22
      oxacalcitriol, in particular, exhibits impressive suppression of parathyroid
      hormone (PTH) with minimal calcemia, although it has been less impressive when
      compared with calcitriol in controlled studies in hemodialysis (HD) patients. The
      advantages of these agents over conventional treatment with calcitriol or
      alfacalcidol remain uncertain. Cinacalcet, a calcimimetic agent that up-regulates
      the sensitivity of the CaSR in parathyroid and other cells, is a new type of
      therapy for SHPT that simultaneously reduces the concentrations of PTH, Ca, and P
      in HD patients, enabling a significant number to achieve K/DOQI or other national
      guidelines. The extent to which this new therapy will improve clinical outcomes
      remains uncertain. In conclusion, with the advent of new therapies the emphasis
      in the management of SHPT has evolved to incorporate reduction of Ca loading,
      control of PTH within specific target ranges, and avoidance of hypercalcemia,
      hyperphosphatemia and elevation of the calcium phosphorus product.

PMID- 16109141
TI  - Impact of sevelamer hydrochloride and the K/DOQI guidelines.
AB  - Sevelamer hydrochloride (SH) was registered as a new drug under the Japanese
      national health insurance scheme in 2003, and the Kidney Disease Outcomes Quality
      Initiative (K/DOQI) guidelines for the treatment of renal osteodystrophy were
      released the same year. At that time, treatment objectives for hemodialysis
      outpatients at the Kojinkai Ishimaki Clinic were settled established and the
      outcomes reviewed 18 months later. The relationship between the type and dosage
      of phosphate binder (PB), and the concentrations of adjusted calcium (Ca),
      phosphorus (P), intact parathyroid hormone (PTH), and bone alkaline phosphatase
      (BAP) was examined. Patients receiving calcitriol or maxacalcitol intravenous
      pulse therapy, or who had undergone simultaneous pancreas-kidney transplant, were
      excluded from this analysis. The PB was CaCO3 in 60% of cases, SH in 33.3%, and a
      combination of both in 21.9%; no PB was used in 6.7% of cases. The dosage of
      CaCO3 was 2.8+/-1.0 g/day, and 1alpha-hydroxy activated vitamin D3 (VD) was
      0.46+/-0.24 microg/day; the respective concentrations of adjusted Ca, P, intact
      PTH, and BAP were 9.4+/-0.7 mg/dL, 5.6+/-1.7 mg/dL, 104+/-83.9 pg/mL, and 22.7+/
      10.9 IU/L. In the SH monotherapy group, the dosage of SH was 3.9+/-0.725 g/day,
      and VD 0.62+/-0.21 microg/day, and the concentrations for adjusted Ca, P, intact
      PTH, and BAP were 9.6+/-0.4 mg/dL, 6.2+/-1.5 mg/dL, 150+/-42.9 pg/mL, and 38.5+/
      14.2 IU/L, respectively. In the combined therapy group, the dosage of CaCO3 was
      2.9+/-0.9 g/day, SH was 3.3+/-1.1 g/day, VD was 0.53+/-0.27 microg/day, and the
      respective concentrations were 9.2+/-1.0 mg/dL, 5.7+/-1.4 mg/dL, 160+/-107.8
      pg/mL, and 31.3+/-42.0 IU/L. One-third of all subjects were administered SH,
      either as monotherapy or in combination with CaCO3, and in these patients the
      dosage of VD was able to increase.

PMID- 16109142
TI  - Abstracts of the 44th Annual Scientific Meeting of the British Society for
      Clinical Cytology. Newcastle upon Tyne, United Kingdom. September 11-14, 2005.

PMID- 16109143
TI  - Negotiation in health libraries: a case study of Health Information and Libraries
      Journal and open access publishing.

PMID- 16109144
TI  - Examination of the impact of information-skills training on the academic work of
      health-studies students: a single case study.
AB  - AIM: To examine the impact of information-skills training on the academic studies
      of student midwives. Objectives include ascertaining whether student confidence
      increases, learning experiences are enhanced and academic standards are improved.
      METHODS: A student midwives' discussion group at a higher education institution,
      plus an in-depth interview with the students' course leader. RESULTS: Students
      reported increased confidence in using library and information resources.
      Appropriate and timely information-skills training embedded into health-studies
      curricula can lead to students becoming independent and lifelong learners, as
      well as improving the standard of their academic work. CONCLUSION: Information
      skills for health-studies curricula in higher education can be developed and
      delivered collaboratively by both library and academic staff. This can have very
      positive effects on both student perceptions and experiences and standards of
      teaching and learning.

PMID- 16109145
TI  - Information-seeking behaviour and use of the Internet by French general
      practitioners: a qualitative study.
AB  - BACKGROUND: Numerous studies deal with the use of computers and the Internet in
      the health sector. Most of these studies show an increase in the use of the new
      technologies in searching for medical information-particularly by patients--but
      these uses remain very heterogeneous and depend on the studies. AIMS: The aim of
      this work was to consider the use of computers by French general practitioners
      (GPs) and to analyse the impact that computerization could have on their
      information-seeking behaviour. METHODS: The nature of the approach used is
      qualitative using interviews. RESULTS: Most of the GPs interviewed are equipped
      with a computer. The policies of the government were supposed to give financial
      incentives for GPs to start using computers for the management of administrative
      procedures, but many physicians do not know how to use the new tools properly.
      Their computers are, in most cases, underused for searching for medical
      information. Most of the time, the Internet sources are thought to be unreliable.
      CONCLUSION: This study sheds light on the use of computers and the preferences of
      GPs in searching for medical information.

PMID- 16109146
TI  - Use of libraries and electronic information resources by primary care staff:
      outcomes from a survey.
AB  - OBJECTIVES: To assess the use of existing libraries; usage of the Internet and
      biomedical databases; and need for training on use of the Internet and biomedical
      databases for primary care staff. METHODS: A postal survey of general
      practitioners (GPs), practice nurses (PNs) and practice managers (PMs) in
      Nottingham and Rotherham, UK. RESULTS: Overall, 243 questionnaires were used. The
      response rate in Nottingham was 24%, in Rotherham it was 34%. Reported use of
      libraries was low (30%), with PNs reporting significantly higher usage (65%) than
      others (P < 0.01). Most respondents reported using the Internet (81%), but fewer
      (44%) reported using databases. GPs and PNs were significantly more likely to
      report using databases than PMs (P < 0.01). Lack of training was the most
      reported barrier to using the Internet (67%) and databases (52%). Overall, 52% of
      respondents reported wanting Internet training, 64% wanted database training. The
      percentages requesting training on databases were high among GPs and PNs, but
      significantly lower for PMs (P = 0.02). CONCLUSIONS: There are differences in the
      usage of libraries and electronic resources among the primary care team, and in
      reported training needs. While the reported levels of usage of the Internet and
      biomedical databases are encouraging, our study identified a training need. If
      met, this could increase usage further.

PMID- 16109147
TI  - Impact of librarians in first-year medical and dental student problem-based
      learning (PBL) groups: a controlled study.
AB  - BACKGROUND: Librarians at the University of Alberta have been involved with
      teaching undergraduate medical and dental education for several years. After 1
      year of increased librarian involvement at the problem-based learning (PBL),
      small-group level, informal feedback from faculty and students suggested that
      librarians' participation in PBL groups was beneficial. There was, however, no
      real evidence to support this claim or justify the high demand on librarians'
      time. OBJECTIVES: The study aimed to determine whether having a librarian present
      in the small-group, problem-based learning modules for first-year medical and
      dental students results in an improved understanding of evidence-based medicine
      concepts, the nature of medical literature, and information access skills.
      METHODS: One hundred and sixty-four first-year medical and dental students
      participated in the study. There were a total of 18 PBL groups, each with
      approximately nine students and one faculty tutor. Six librarians participated
      and were assigned randomly to the six intervention groups. Students were given
      pre- and post-tests at the outset and upon completion of the 6-week course.
      RESULTS: Post-test scores showed that there was a small positive librarian
      impact, but final exam scores showed no impact. There was also no difference in
      attitudes or comfort levels between students who had a librarian in their group
      and those who did not. CONCLUSIONS: Impact was not sufficient to warrant
      continued participation of librarians in PBL. In future instruction, librarians
      at the John W. Scott Health Sciences Library will continue to teach at the larger
      group level.

PMID- 16109148
TI  - Information needs of United Kingdom primary care clinicians.
AB  - BACKGROUND: The scope of primary care makes knowledge management in this context
      very challenging, especially as access to information increases and the role of
      primary care within the NHS expands. OBJECTIVES: This paper reviews the
      literature on the information needs of primary care clinicians to enable evidence
      based decision making. Drawing on the literature, and using a specific example of
      a clinical informaticist service, some lessons are drawn on the role of
      information professionals in facilitating evidence-based health care. METHODS:
      Literature review. Case study of clinical informaticist service. CONCLUSIONS:
      There are numerous barriers to clinicians engaging with evidence-based practice.
      However, providing evidence-based information to clinicians' questions in a user
      friendly format has the potential to facilitate changes in practice. The
      successful implementation of information services requires attention to both
      academic and service dimensions, fostering closer working relationships between
      clinicians and information professionals.

PMID- 16109150
TI  - Union catalogues of health-sciences journals in the Eastern Mediterranean Region
      (EMR) of the World Health Organization (WHO).

PMID- 16109149
TI  - Australian occupational therapists' use of an online evidence-based practice
      database (OTseeker).
AB  - INTRODUCTION: Online databases can support the implementation of evidence-based
      practice by providing easy access to research. OTseeker
      (http://www.otseeker.com), an electronic evidence database, was introduced in
      2003 to assist occupational therapists to locate and interpret research.
      OBJECTIVES: This study explored Australian occupational therapists' use and
      perceptions of OTseeker and its impact on their knowledge and practice. METHODS:
      A postal survey questionnaire was distributed to two samples: (i) a proportionate
      random sample of 400 occupational therapists from all states and territories of
      Australia, and (ii) a random sample of occupational therapists working in 95
      facilities in two Australian states (Queensland and New South Wales). RESULTS:
      The questionnaire was completed by 213 participants. While most participants
      (85.9%) had heard of OTseeker, only 103 (56.6%) had accessed it, with lack of
      time being the main reason for non-use. Of the 103 participants who had accessed
      OTseeker, 68.9% had done so infrequently, 63.1% agreed that it had increased
      their knowledge and 13.6% had changed their practice after accessing information
      on OTseeker. CONCLUSION: Despite OTseeker being developed to provide occupational
      therapists with easy access to research, lack of time was the main reason why
      over half of the participants in this study had not accessed it. This exploratory
      research suggests, however, that there is potential for the database to influence
      occupational therapists' knowledge and practice about treatment efficacy through
      access to the research literature.

PMID- 16109151
TI  - Helping doctors put patients first: an innovative service from health libraries.

PMID- 16109152
TI  - Searching a biomedical bibliographic database from the Ukraine: the Panteleimon
      database.

PMID- 16109153
TI  - Mind your Ps and Qs (pitfalls of questionnaires).

PMID- 16109155
TI  - Charles Frank Albert Marmoy 1909-2005.

PMID- 16109157
TI  - Health disparities and advertising content of women's magazines: a cross
      sectional study.
AB  - BACKGROUND: Disparities in health status among ethnic groups favor the Caucasian
      population in the United States on almost all major indicators. Disparities in
      exposure to health-related mass media messages may be among the environmental
      factors contributing to the racial and ethnic imbalance in health outcomes. This
      study evaluated whether variations exist in health-related advertisements and
      health promotion cues among lay magazines catering to Hispanic, African American
      and Caucasian women. METHODS: Relative and absolute assessments of all health
      related advertising in 12 women's magazines over a three-month period were
      compared. The four highest circulating, general interest magazines oriented to
      Black women and to Hispanic women were compared to the four highest-circulating
      magazines aimed at a mainstream, predominantly White readership. Data were
      collected and analyzed in 2002 and 2003. RESULTS: Compared to readers of
      mainstream magazines, readers of African American and Hispanic magazines were
      exposed to proportionally fewer health-promoting advertisements and more health
      diminishing advertisements. Photographs of African American role models were more
      often used to advertise products with negative health impact than positive health
      impact, while the reverse was true of Caucasian role models in the mainstream
      magazines. CONCLUSION: To the extent that individual levels of health education
      and awareness can be influenced by advertising, variations in the quantity and
      content of health-related information among magazines read by different ethnic
      groups may contribute to racial disparities in health behaviors and health
      status.

PMID- 16109158
TI  - Acute bronchiolitis in infancy as risk factor for wheezing and reduced pulmonary
      function by seven years in Akershus County, Norway.
AB  - BACKGROUND: Acute viral bronchiolitis is one of the most common causes of
      hospitalisation during infancy in our region with respiratory syncytial virus
      (RSV) historically being the major causative agent. Many infants with early-life
      RSV bronchiolitis have sustained bronchial hyperreactivity for many years after
      hospitalisation and the reasons for this are probably multifactorial. The
      principal aim of the present study was to investigate if children hospitalised
      for any acute viral bronchiolitis during infancy in our region, and not only
      those due to RSV, had more episodes of subsequent wheezing up to age seven years
      and reduced lung function at that age compared to children not hospitalised for
      acute bronchiolitis during infancy. A secondary aim was to compare the
      hospitalised infants with proven RSV bronchiolitis (RS+) to the hospitalised
      infants with non-RSV bronchiolitis (RS-) according to the same endpoints.
      METHODS: 57 infants hospitalised at least once with acute viral bronchiolitis
      during two consecutive winter seasons in 1993-1994 were examined at age seven
      years. An age-matched control group of 64 children, who had not been hospitalised
      for acute viral bronchiolitis during infancy, were recruited from a local primary
      school. Epidemiological and clinical data were collected retrospectively from
      hospital discharge records and through structured clinical interviews and
      physical examinations at the follow-up visit. RESULTS: The children hospitalised
      for bronchiolitis during infancy had decreased lung function, more often wheezing
      episodes, current medication and follow-up for asthma at age seven years than did
      the age matched controls. They also had lower average birth weight and more often
      first order family members with asthma. We did not find significant differences
      between the RSV+ and RSV- groups. CONCLUSION: Children hospitalised for early
      life bronchiolitis are susceptible to recurrent wheezing and reduced pulmonary
      function by seven years compared to age-matched children not hospitalised for
      early-life bronchiolitis. We propose that prolonged bronchial hyperreactivity
      could follow early-life RSV negative as well as RSV positive bronchiolitis.

PMID- 16109159
TI  - Falls in young, middle-aged and older community dwelling adults: perceived cause,
      environmental factors and injury.
AB  - BACKGROUND: Falls in older people have been characterized extensively in the
      literature, however little has been reported regarding falls in middle-aged and
      younger adults. The objective of this paper is to describe the perceived cause,
      environmental influences and resultant injuries of falls in 1497 young (20-45
      years), middle-aged (46-65 years) and older (> 65 years) men and women from the
      Baltimore Longitudinal Study on Aging. METHODS: A descriptive study where
      participants completed a fall history questionnaire describing the circumstances
      surrounding falls in the previous two years. RESULTS: The reporting of falls
      increased with age from 18% in young, to 21% in middle-aged and 35% in older
      adults, with higher rates in women than men. Ambulation was cited as the cause of
      the fall most frequently in all gender and age groups. Our population reported a
      higher percentage of injuries (70.5%) than previous studies. The young group
      reported injuries most frequently to wrist/hand, knees and ankles; the middle
      aged to their knees and the older group to their head and knees. Women reported a
      higher percentage of injuries in all age groups. CONCLUSION: This is the first
      study to compare falls in young, middle and older aged men and women. Significant
      differences were found between the three age groups with respect to number of
      falls, activities engaged in prior to falling, perceived causes of the fall and
      where they fell.

PMID- 16109160
TI  - The effect of a monetary incentive on return of a postal health and development
      questionnaire: a randomised trial [ISRCTN53994660].
AB  - BACKGROUND: Postal questionnaires are widely used to collect data in healthcare
      research but a poor response rate may reduce the validity and reliability of
      results. There was a lack of evidence available relating to use of a monetary
      incentive to improve the response rate in the healthcare setting. METHODS: The
      MRC ORACLE Children Study is assessing the health and development of nearly 9000
      seven year old children whose mothers' joined the MRC ORACLE Trial. We carried
      out a randomised controlled trial of inclusion of monetary incentive (five pound
      voucher redeemable at many high street stores) with the reminder questionnaire to
      parents. This trial took place between April 2002 and November 2003. When the
      parents were sent the reminder questionnaire about their child's health and
      development they were randomly assigned by concealed computer-generated
      allocation stratified by week of birthday to receive a five pound voucher or no
      incentive. The population were 722 non-responders to the initial mailing of a 12
      page questionnaire. MAIN OUTCOME MEASURES: Difference in response rate between
      the two groups. RESULTS: Inclusion of the voucher with the reminder questionnaire
      resulted in a 11.7%(95% CI 4.7% to 18.6%) improvement in the response rate
      between the two groups. CONCLUSION: This improvement in response rate and hence
      the validity and reliability of results obtained appears to be justified
      ethically and financially.

PMID- 16109161
TI  - An ancient spliceosomal intron in the ribosomal protein L7a gene (Rpl7a) of
      Giardia lamblia.
AB  - BACKGROUND: Only one spliceosomal-type intron has previously been identified in
      the unicellular eukaryotic parasite, Giardia lamblia (a diplomonad). This intron
      is only 35 nucleotides in length and is unusual in possessing a non-canonical 5'
      intron boundary sequence, CT, instead of GT. RESULTS: We have identified a second
      spliceosomal-type intron in G. lamblia, in the ribosomal protein L7a gene
      (Rpl7a), that possesses a canonical GT 5' intron boundary sequence. A comparison
      of the two known Giardia intron sequences revealed extensive nucleotide identity
      at both the 5' and 3' intron boundaries, similar to the conserved sequence motifs
      recently identified at the boundaries of spliceosomal-type introns in Trichomonas
      vaginalis (a parabasalid). Based on these observations, we searched the partial
      G. lamblia genome sequence for these conserved features and identified a third
      spliceosomal intron, in an unassigned open reading frame. Our comprehensive
      analysis of the Rpl7a intron in other eukaryotic taxa demonstrates that it is
      evolutionarily conserved and is an ancient eukaryotic intron. CONCLUSION: An
      analysis of the phylogenetic distribution and properties of the Rpl7a intron
      suggests its utility as a phylogenetic marker to evaluate particular eukaryotic
      groupings. Additionally, analysis of the G. lamblia introns has provided further
      insight into some of the conserved and unique features possessed by the recently
      identified spliceosomal introns in related organisms such as T. vaginalis and
      Carpediemonas membranifera.

PMID- 16109162
TI  - A priori postulated and real power in cluster randomized trials: mind the gap.
AB  - BACKGROUND: Cluster randomization design is increasingly used for the evaluation
      of health-care, screening or educational interventions. The intraclass
      correlation coefficient (ICC) defines the clustering effect and be specified
      during planning. The aim of this work is to study the influence of the ICC on
      power in cluster randomized trials. METHODS: Power contour graphs were drawn to
      illustrate the loss in power induced by an underestimation of the ICC when
      planning trials. We also derived the maximum achievable power given a specified
      ICC. RESULTS: The magnitude of the ICC can have a major impact on power, and with
      low numbers of clusters, 80% power may not be achievable. CONCLUSION:
      Underestimating the ICC during planning cluster randomized trials can lead to a
      seriously underpowered trial. Publication of a priori postulated and a posteriori
      estimated ICCs is necessary for a more objective reading: negative trial results
      may be the consequence of a loss of power due to a mis-specification of the ICC.

PMID- 16109163
TI  - Acupuncture for dyspnea in advanced cancer: a randomized, placebo-controlled
      pilot trial [ISRCTN89462491].
AB  - BACKGROUND: Dyspnea, or shortness of breath, is a common symptom in patients with
      advanced cancer. Pharmacologic management is of proven benefit, but it does not
      help all patients. Preliminary data suggest that acupuncture can relieve dyspnea
      in a variety of populations, including cancer patients. We conducted a pilot
      study (ISRCTN89462491) preparatory to a fully powered randomized, placebo
      controlled trial to determine whether acupuncture reduces dyspnea in patients
      with lung or breast cancer. METHODS: The study sample was comprised of forty
      seven patients with lung or breast cancer presenting with dyspnea. Patients
      receiving symptomatic treatments were not excluded as long as no changes in
      management were planned during the trial. Patients were randomized to receive a
      single session of true or placebo acupuncture in addition to their existing
      dyspnea treatments. Semi-permanent acupuncture "studs" were then inserted:
      patients applied pressure to these studs twice a day to provide ongoing
      stimulation to acupuncture points. The subjective sensation of dyspnea was
      assessed with a 0-10 numerical rating scale immediately before and after
      acupuncture treatment and daily for a week thereafter. RESULTS: All but two of 47
      randomized patients provided follow-up data. Dyspnea scores were slightly higher
      for patients receiving true versus placebo acupuncture, for both the period
      immediately following acupuncture treatment and for the daily one week follow-up
      (differences between means of 0.34, 95% C.I. -0.33, 1.02 and 0.56, 95% C.I. 
      0.39, 1.51). The 95% confidence interval excludes the prespecified minimum
      clinically significant difference of a 20% greater improvement in dyspnea for
      patients receiving acupuncture. CONCLUSION: The acupuncture technique used in
      this trial is unlikely to have effects on dyspnea importantly larger than placebo
      for patients with advanced cancer.

PMID- 16109164
TI  - Herpes simplex virus interferes with amyloid precursor protein processing.
AB  - BACKGROUND: The early events underlying Alzheimer's disease (AD) remain
      uncertain, although environmental factors may be involved. Work in this
      laboratory has shown that the combination of herpes simplex virus type 1 (HSV1)
      in brain and carriage of the APOE-epsilon4 allele of the APOE gene strongly
      increases the risk of developing AD. The development of AD is thought to involve
      abnormal aggregation or deposition of a 39-43 amino acid protein--beta amyloid
      (Abeta)--within the brain. This is cleaved from the much larger transmembranal
      protein 'amyloid precursor protein' (APP). Any agent able to interfere directly
      with Abeta or APP metabolism may therefore have the capacity to contribute
      towards AD. One recent report showed that certain HSV1 glycoprotein peptides may
      aggregate like Abeta; a second study described a role for APP in transport of
      virus in squid axons. However to date the effects of acute herpesvirus infection
      on metabolism of APP in human neuronal-type cells have not been investigated. In
      order to find if HSV1 directly affects APP and its degradation, we have examined
      this protein from human neuroblastoma cells (normal and transfected with APP 695)
      infected with the virus, using Western blotting. RESULTS: We have found that
      acute HSV1 (and also HSV2) infection rapidly reduces full length APP levels--as
      might be expected--yet surprisingly markedly increases levels of a novel C
      terminal fragment of APP of about 55 kDa. This band was not increased in cells
      treated with the protein synthesis inhibitor cycloheximide CONCLUSION: Herpes
      virus infection leads to rapid loss of full length APP from cells, yet also
      causes increased levels of a novel 55 kDa C-terminal APP fragment. These data
      suggest that infection can directly alter the processing of a transmembranal
      protein intimately linked to the aetiology of AD.

PMID- 16109165
TI  - Inducible nitric oxide synthase (iNOS) expression in monocytes during acute
      Dengue Fever in patients and during in vitro infection.
AB  - Mononuclear phagocytes are considered to be main targets for Dengue Virus (DENV)
      replication. These cells are activated after infection, producing proinflammatory
      mediators, including tumour-necrosis factor-alpha, which has also been detected
      in vivo. Nitric oxide (NO), usually produced by activated mononuclear phagocytes,
      has antimicrobial and antiviral activities. METHODS: The expression of DENV
      antigens and inducible nitric oxide synthase (iNOS) in human blood isolated
      monocytes were analysed by flow cytometry using cells either from patients with
      acute Dengue Fever or after DENV-1 in vitro infection. DENV-1 susceptibility to
      iNOS inhibition and NO production was investigated using NG-methyl L-Arginine
      (NGMLA) as an iNOS inhibitor, which was added to DENV-1 infected human monocytes,
      and sodium nitroprussiate (SNP), a NO donor, added to infected C6/36 mosquito
      cell clone. Viral antigens after treatments were detected by flow cytometry
      analysis. RESULTS: INOS expression in activated monocytes was observed in 10 out
      of 21 patients with Dengue Fever and was absent in cells from ten healthy
      individuals. DENV antigens detected in 25 out of 35 patients, were observed early
      during in vitro infection (3 days), significantly diminished with time,
      indicating that virus replicated, however monocytes controlled the infection. On
      the other hand, the iNOS expression was detected at increasing frequency in in
      vitro infected monocytes from three to six days, exhibiting an inverse
      relationship to DENV antigen expression. We demonstrated that the detection of
      the DENV-1 antigen was enhanced during monocyte treatment with NGMLA. In the
      mosquito cell line C6/36, virus detection was significantly reduced in the
      presence of SNP, when compared to that of untreated cells. CONCLUSION: This study
      is the first to reveal the activation of DENV infected monocytes based on
      induction of iNOS both in vivo and in vitro, as well as the susceptibility of
      DENV-1 to a NO production.

PMID- 16109166
TI  - A simplified immunoprecipitation method for quantitatively measuring antibody
      responses in clinical sera samples by using mammalian-produced Renilla luciferase
      antigen fusion proteins.
AB  - BACKGROUND: Assays detecting human antigen-specific antibodies are medically
      useful. However, the usefulness of existing simple immunoassay formats is limited
      by technical considerations such as sera antibodies to contaminants in
      insufficiently pure antigen, a problem likely exacerbated when antigen panels are
      screened to obtain clinically useful data. RESULTS: We developed a novel and
      simple immunoprecipitation technology for identifying clinical sera containing
      antigen-specific antibodies and for generating quantitative antibody response
      profiles. This method is based on fusing protein antigens to an enzyme reporter,
      Renilla luciferase (Ruc), and expressing these fusions in mammalian cells, where
      mammalian-specific post-translational modifications can be added. After mixing
      crude extracts, sera and protein A/G beads together and incubating, during which
      the Ruc-antigen fusion become immobilized on the A/G beads, antigen-specific
      antibody is quantitated by washing the beads and adding coelenterazine substrate
      and measuring light production. We have characterized this technology with sera
      from patients having three different types of cancers. We show that 20-85% of
      these sera contain significant titers of antibodies against at least one of five
      frequently mutated and/or overexpressed tumor-associated proteins. Five of six
      colon cancer sera tested gave responses that were statistically significantly
      greater than the average plus three standard deviations of 10 control sera. The
      results of competition experiments, preincubating positive sera with unmodified
      E. coli-produced antigens, varied dramatically. CONCLUSION: This technology has
      several advantages over current quantitative immunoassays including its relative
      simplicity, its avoidance of problems associated with E. coli-produced antigens
      and its use of antigens that can carry mammalian or disease-specific post
      translational modifications. This assay should be generally useful for analyzing
      sera for antibodies recognizing any protein or its post-translational
      modifications.

PMID- 16109167
TI  - Enhanced efficacy of gemcitabine in combination with anti-CD20 monoclonal
      antibody against CD20+ non-Hodgkin's lymphoma cell lines in vitro and in scid
      mice.
AB  - BACKGROUND: Despite exciting new targeted therapeutics against non-Hodgkin's
      lymphoma (NHL), chemotherapy remains a cornerstone of therapy. While purine
      nucleoside analogs have significant activity in low grade NHL, the pyrimidine
      nucleoside analog gemcitabine has been less extensively studied, but has
      important activity. Use of the anti-CD20 monoclonal antibody rituximab in
      combination with chemotherapy for B-NHL is becoming prevalent in clinical
      practice, but has not been extensively studied in pre-clinical models. METHODS:
      We have tested the activity of gemcitabine +/- rituximab in vitro and in
      scid/human NHL xenograft models. We used two t(14;18)+, CD20+ follicular B cell
      NHL cell lines, DoHH2 a transformed NHL line and WSU-FSCCL isolated from pleural
      fluid of a patient with indolent NHL. RESULTS: Gemcitabine is cytotoxic to DoHH2
      and WSU-FSCCL cells in vitro, and the IC50 is 2-3 fold lower in the presence of
      rituximab. Apoptosis is also enhanced in the presence of rituximab. Clearance of
      NHL cells from ascites in scid mice is prolonged by the combination, as compared
      with either agent alone. Most importantly, survival of scid mice bearing human
      NHL cells is significantly prolonged by the combination of gemcitabine +
      rituximab. CONCLUSION: Based on our pre-clinical data showing prolonged survival
      of mice bearing human lymphoma cell line xenografts after treatment with
      gemcitabine + anti-CD20 antibody, this combination, expected to have non
      overlapping toxicity profiles, should be explored in clinical trials.

PMID- 16109168
TI  - In vivo antimuscarinic actions of the third generation antihistaminergic agent,
      desloratadine.
AB  - BACKGROUND: Muscarinic receptor mediated adverse effects, such as sedation and
      xerostomia, significantly hinder the therapeutic usefulness of first generation
      antihistamines. Therefore, second and third generation antihistamines which
      effectively antagonize the H1 receptor without significant affinity for
      muscarinic receptors have been developed. However, both in vitro and in vivo
      experimentation indicates that the third generation antihistamine, desloratadine,
      antagonizes muscarinic receptors. To fully examine the in vivo antimuscarinic
      efficacy of desloratadine, two murine and two rat models were utilized. The
      murine models sought to determine the efficacy of desloratadine to antagonize
      muscarinic agonist induced salivation, lacrimation, and tremor. Desloratadine's
      effect on the cardiovascular system was explored in both rodent models. RESULTS:
      In the pithed rat, both desloratadine (1.0 mg/kg, i.v.) and the muscarinic M2
      selective antagonist, methoctramine (0.5 mg/kg, i.v.), inhibited negative
      inotropic (left ventricular dP/dt) effects caused by oxotremorine, a nonselective
      muscarinic agonist (p < 0.05). Negative chronotropic effects caused by
      oxotremorine were inhibited by desloratadine, methoctramine, and the muscarinic
      M3 selective antagonist, 4-DAMP (1.0 mg/kg, i.v.). A late positive inotropic
      event observed after the initial decrease was inhibited by all three test
      compounds with desloratadine and 4-DAMP being the most efficacious. In the
      conscious animal, inhibition of baroreflex-mediated bradycardia was evaluated.
      Unlike atropine (0.5 mg/kg, i.v.), desloratadine did not alter this bradycardia.
      The antimuscarinic action of desloratadine on salivation, lacrimation, and tremor
      was also explored. In urethane-anesthetized (1.5 g/kg, i.p.) male ICR mice (25-35
      g) desloratadine (1.0, 5.0 mg/kg) did not inhibit oxotremorine-induced (0.5
      mg/kg, s.c.) salivation, unlike atropine (0.5 mg/kg) and 4-DAMP (1.0 mg/kg). In
      conscious mice, desloratadine failed to inhibit oxotremorine-induced (0.5 mg/kg,
      s.c.) salivation, lacrimation, and tremor. However, desloratadine did inhibit
      oxotremorine-induced tremor in phenylephrine pretreated animals. CONCLUSION: The
      presented data demonstrate that the third generation antihistamine,
      desloratadine, does not significantly antagonize peripheral muscarinic receptors
      mediating salivation and lacrimation, therefore, xerostomia and dry eyes should
      not be observed with therapeutic use of desloratadine. Our data also indicate
      when administered to a patient with a compromised blood-brain barrier,
      desloratadine may cause sedation. Patients with compromised cardiovascular
      systems should be closely monitored when administered desloratadine based on our
      results that desloratadine has the ability to interfere with normal
      cardiovascular function mediated by muscarinic receptors.

PMID- 16109169
TI  - Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak
      formation and early patterning of the mouse embryo.
AB  - BACKGROUND: Huntingtin, the HD gene encoded protein mutated by polyglutamine
      expansion in Huntington's disease, is required in extraembryonic tissues for
      proper gastrulation, implicating its activities in nutrition or patterning of the
      developing embryo. To test these possibilities, we have used whole mount in situ
      hybridization to examine embryonic patterning and morphogenesis in homozygous
      Hdh(ex4/5) huntingtin deficient embryos. RESULTS: In the absence of huntingtin,
      expression of nutritive genes appears normal but E7.0-7.5 embryos exhibit a
      unique combination of patterning defects. Notable are a shortened primitive
      streak, absence of a proper node and diminished production of anterior streak
      derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial
      mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of
      head development. In addition, genes initially broadly expressed are not properly
      restricted to the posterior, as evidenced by the ectopic expression of Nodal,
      Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm
      derivatives. Despite impaired posterior restriction and anterior streak deficits,
      overall anterior/posterior polarity is established. A single primitive streak
      forms and marker expression shows that the anterior epiblast and anterior
      visceral endoderm (AVE) are specified. CONCLUSION: Huntingtin is essential in the
      early patterning of the embryo for formation of the anterior region of the
      primitive streak, and for down-regulation of a subset of dynamic growth and
      transcription factor genes. These findings provide fundamental starting points
      for identifying the novel cellular and molecular activities of huntingtin in the
      extraembryonic tissues that govern normal anterior streak development. This
      knowledge may prove to be important for understanding the mechanism by which the
      dominant polyglutamine expansion in huntingtin determines the loss of neurons in
      Huntington's disease.

PMID- 16109170
TI  - Expression of G-protein inwardly rectifying potassium channels (GIRKs) in lung
      cancer cell lines.
AB  - BACKGROUND: Previous data from our laboratory has indicated that there is a
      functional link between the beta-adrenergic receptor signaling pathway and the G
      protein inwardly rectifying potassium channel (GIRK1) in human breast cancer cell
      lines. We wanted to determine if GIRK channels were expressed in lung cancers and
      if a similar link exists in lung cancer. METHODS: GIRK1-4 expression and levels
      were determined by reverse transcription polymerase chain reaction (RT-PCR) and
      real-time PCR. GIRK protein levels were determined by western blots and cell
      proliferation was determined by a 5-bromo-2'-deoxyuridine (BrdU) assay. RESULTS:
      GIRK1 mRNA was expressed in three of six small cell lung cancer (SCLC) cell
      lines, and either GIRK2, 3 or 4 mRNA expression was detected in all six SCLC cell
      lines. Treatment of NCI-H69 with beta2-adrenergic antagonist ICI 118,551 (100
      microM) daily for seven days led to slight decreases of GIRK1 mRNA expression
      levels. Treatment of NCI-H69 with the beta-adrenergic agonist isoproterenol (10
      microM) decreased growth rates in these cells. The GIRK inhibitor U50488H (2
      microM) also inhibited proliferation, and this decrease was potentiated by
      isoproterenol. In the SCLC cell lines that demonstrated GIRK1 mRNA expression, we
      also saw GIRK1 protein expression. We feel these may be important regulatory
      pathways since no expression of mRNA of the GIRK channels (1 & 2) was found in
      hamster pulmonary neuroendocrine cells, a suggested cell of origin for SCLC, nor
      was GIRK1 or 2 expression found in human small airway epithelial cells. GIRK
      (1,2,3,4) mRNA expression was also seen in A549 adenocarcinoma and NCI-H727
      carcinoid cell lines. GIRK1 mRNA expression was not found in tissue samples from
      adenocarcinoma or squamous cancer patients, nor was it found in NCI-H322 or NCI
      H441 adenocarcinoma cell lines. GIRK (1,3,4) mRNA expression was seen in three
      squamous cell lines, GIRK2 was only expressed in one squamous cell line. However,
      GIRK1 protein expression was not seen in any non-SCLC cells. CONCLUSION: We feel
      that this data may indicate that stimulation of GIRK1 or GIRK2 channels may be
      important in lung cancer. Stimulation of GIRK channels and beta-adrenergic
      signaling may activate similar signaling pathways in both SCLC and breast cancer,
      but lead to different results.

PMID- 16109171
TI  - In B-CLL, the codon 72 polymorphic variants of p53 are not related to drug
      resistance and disease prognosis.
AB  - BACKGROUND: A common sequence polymorphism at codon 72 of the p53 gene encoding
      either arginine or proline was recently shown to be functionally relevant for
      apoptosis induction in vitro. In B-type chronic lymphocytic leukemia (B-CLL), p53
      gene mutations occur in a subset of patients and are associated with impaired
      survival and drug resistance. Here, we address the functional relevance of the
      codon 72 single nucleotide (SNP) polymorphism for cell death sensitivity
      following exposure to clinically employed cytotoxic drugs and gamma-irradiation.
      METHODS: 138 B-CLL samples were analysed by SSCP-PCR and sequencing for single
      nucleotide polymorphism at codon 72 of the p53 gene. The in vitro cytotoxicity
      assay (DiSC-assay) was performed with 7 drugs (chlorambucil, mafosfamide,
      fludarabine phosphate, methylprednisolone, doxorubicin, vincristine) or gamma
      irradiation. RESULTS: Of the 138 B-CLL samples, 9 samples were homozygous for
      proline (Pro/Pro), 78 samples homozygous for arginine (Arg/Arg), and 49 samples
      heterozygous (Arg/Pro). No differences were found for patient survival and cell
      death triggered by 7 cytotoxic drugs or gamma-irradiation. CONCLUSION: These data
      indicate that polymorphic variants of p53 codon 72 are not clinically relevant
      for apoptosis induction or patient survival in B-CLL.

PMID- 16109172
TI  - CXCR4 and CCR5 shRNA transgenic CD34+ cell derived macrophages are functionally
      normal and resist HIV-1 infection.
AB  - BACKGROUND: Stable simultaneous knock down of the HIV-1 coreceptors CCR5 and
      CXCR4 is a promising strategy to protect cells from both R5 macrophage tropic and
      X4 T cell tropic as well as dual tropic viral infections. The potency of shRNAs
      in targeted gene silencing qualifies them as powerful tools for long term HIV
      gene therapy. Our previous work with a bispecific lentiviral vector containing
      CXCR4 and CCR5 shRNAs showed efficacy in down regulating both coreceptors and
      conferring viral resistance to both X4 and R5-tropic strains of HIV-1 in cultured
      cell lines. To extend these results to a stem cell gene therapy setting, here we
      show transduction of primary CD34+ hematopoietic progenitor cells to derive
      normal end stage cells that are resistant to HIV-1 infection. RESULTS: The
      bispecific XHR lentiviral vector harboring CXCR4 and CCR5 shRNA expression
      cassettes was efficient in transducing CD34+ cells. The transduced cells gave
      rise to morphologically normal transgenic macrophages when cultured in cytokine
      media. There was a marked down regulation of both coreceptors in the stably
      transduced macrophages which showed resistance to both R5 and X4 HIV-1 strains
      upon in vitro challenge. Since off target effects by some shRNAs may have adverse
      effects on transgenic cells, the stably transduced macrophages were further
      analyzed to determine if they are phenotypically and functionally normal. FACS
      evaluation showed normal levels of the characteristic surface markers CD14, CD4,
      MHC class II, and B7.1. Phagocytic functions were also normal. The transgenic
      macrophages demonstrated normal abilities in up-regulating the costimulatory
      molecule B7.1 upon LPS stimulation. Furthermore, IL-1 and TNFalpha cytokine
      secretion in response to LPS stimulation was also normal. Thus, the transgenic
      macrophages appear to be phenotypically and functionally normal. CONCLUSION:
      These studies have demonstrated for the first time that a bispecific lentiviral
      vector could be used to stably deliver shRNAs targeted to both CCR5 and CXCR4
      coreceptors into CD34+ hematopoietic progenitor cells and derive transgenic
      macrophages. Transgenic macrophages with down regulated coreceptors were
      resistant to both R5 and X4 tropic HIV-1 infections. The differentiated cells
      were also phenotypically and functionally normal indicating no adverse effects of
      shRNAs on lineage specific differentiation of stem cells. It is now possible to
      construct gene therapeutic lentiviral vectors incorporating multiple shRNAs
      targeted to cellular molecules that aid in HIV-1 infection. Use of these vectors
      in a stem cell setting shows great promise for sustained HIV/AIDS gene therapy.

PMID- 16109173
TI  - Psoriasis vulgaris flare during efalizumab therapy does not preclude future use:
      a case series.
AB  - BACKGROUND: Severe psoriasis vulgaris can be extremely difficult to treat in some
      patients, even with the newer biological therapies available today. CASE
      PRESENTATIONS: We present two patients with severe chronic plaque psoriasis who
      received numerous systemic anti-psoriatic therapies with varied results. Both
      responded well to initial treatment with efalizumab (anti-CD11a), but then
      experienced a flare of their disease after missing a dose. However, after disease
      stablization, both patients responded well to re-introduction of efalizumab, one
      patient requiring concurrent treatment with infliximab (anti-TNF-alpha).
      CONCLUSION: These cases are presented to characterize this "flare" reaction, and
      to inform health care providers that efalizumab can still be administered after
      disease flare, and again may be a successful therapy.

PMID- 16109174
TI  - Contemporary specificities of labour in the health care sector: introductory
      notes for discussion.
AB  - BACKGROUND: This paper combines the literature on public health, on economics of
      health and on economics of technological innovation to discuss the peculiarities
      of labour in the health care sector. METHOD AND FRAMEWORK: The starting point is
      the investigation of the economic peculiarities of medical care. RESULTS AND
      DISCUSSIONS: This investigation leads to the identification of the prevalence of
      non-market forms of medical care in the countries of the Organisation for
      Economic Co-operation and Development (OECD). Furthermore, the health care system
      has a distinctive characteristic from other economic sectors: it is the
      intersection between social welfare and innovation systems. The relationship
      between technological innovation and cost in the health care sector is surveyed.
      Finally, the Brazilian case is discussed as an example of a developing country.
      CONCLUSION: The peculiarities of labour in the health care sector suggest the
      need to recognize the worth of sectoral labour and to cease to treat it
      separately. This process should take into account the rapid development of the
      health innovation system and one important consequence: the obsolescence of the
      acquired knowledge. One way to dignify labour is to implement continued education
      and training of health professions personnel.

PMID- 16109175
TI  - Expression and subcellular localization of aquaporin water channels in the
      polarized hepatocyte cell line, WIF-B.
AB  - BACKGROUND: Recent data suggest that canalicular bile secretion involves
      selective expression and coordinated regulation of aquaporins (AQPs), a family of
      water channels proteins. In order to further characterize the role of AQPs in
      this process, an in vitro cell system with retained polarity and expression of
      AQPs and relevant solute transporters involved in bile formation is highly
      desirable. The WIF-B cell line is a highly differentiated and polarized rat
      hepatoma/human fibroblast hybrid, which forms abundant bile canalicular
      structures. This cell line has been reported to be a good in vitro model for
      studying hepatocyte polarity. RESULTS: Using RT-PCR, immunoblotting and confocal
      immunofluorescence, we showed that WIF-B cells express the aquaporin water
      channels that facilitate the osmotically driven water movements in the liver,
      i.e. AQP8, AQP9, and AQP0; as well as the key solute transporters involved in the
      generation of canalicular osmotic gradients, i.e., the bile salt export pump
      Bsep, the organic anion transporter Mrp2 and the chloride bicarbonate exchanger
      AE2. The subcellular localization of the AQPs and the solute transporters in WIF
      B cells was similar to that in freshly isolated rat hepatocytes and in intact
      liver. Immunofluorescent costaining studies showed intracellular colocalization
      of AQP8 and AE2, suggesting the possibility that these transporters are expressed
      in the same population of pericanalicular vesicles. CONCLUSION: The hepatocyte
      cell line WIF-B retains the expression and subcellular localization of aquaporin
      water channels as well as key solute transporters for canalicular bile secretion.
      Thus, these cells can work as a valuable tool for regulatory and mechanistic
      studies of the biology of bile formation.

PMID- 16109176
TI  - The therapeutic effect of clinical trials: understanding placebo response rates
      in clinical trials--a secondary analysis.
AB  - BACKGROUND AND PURPOSE: Placebo response rates in clinical trials vary
      considerably and are observed frequently. For new drugs it can be difficult to
      prove effectiveness superior to placebo. It is unclear what contributes to
      improvement in the placebo groups. We wanted to clarify, what elements of
      clinical trials determine placebo variability. METHODS: We analysed a
      representative sample of 141 published long-term trials (randomized, double
      blind, placebo-controlled; duration > 12 weeks) to find out what study
      characteristics predict placebo response rates in various diseases. Correlational
      and regression analyses with study characteristics and placebo response rates
      were carried out. RESULTS: We found a high and significant correlation between
      placebo and treatment response rate across diseases (r = .78; p < .001). A
      multiple regression model explained 79% of the variance in placebo variability (F
      = 59.7; p < 0.0001). Significant predictors are, among others, the duration of
      the study (beta = .31), the quality of the study (beta = .18), the fact whether a
      study is a prevention trial (beta = .44), whether dropouts have been documented
      (beta = -.20), or whether additional treatments have been documented (beta = 
      .17). Healing rates with placebo are lower in the following diagnoses; neoplasms
      (beta = -.21), nervous diseases (beta = -.10), substance abuse (beta = -.14).
      Without prevention trials the amount of variance explained is 42%. CONCLUSION:
      Medication response rates and placebo response rates in clinical trials are
      highly correlated. Trial characteristics can explain some portion of the variance
      in placebo healing rates in RCTs. Placebo response in trials is only partially
      due to methodological artefacts and only partially dependent on the diagnoses
      treated.

PMID- 16109177
TI  - Handheld computers and the 21st century surgical team: a pilot study.
AB  - BACKGROUND: The commercial development and expansion of mobile phone networks has
      led to the creation of devices combining mobile phones and personal digital
      assistants, which could prove invaluable in a clinical setting. This pilot study
      aimed to look at how one such device compared with the current pager system in
      facilitating inter-professional communication in a hospital clinical team.
      METHODS: The study looked at a heterogeneous team of doctors (n = 9) working in a
      busy surgical setting at St. Mary's Hospital in London and compared the use of a
      personal digital assistant with mobile phone and web-browsing facilities to the
      existing pager system. The primary feature of this device being compared to the
      conventional pager was its use as a mobile phone, but other features evaluated
      included the ability to access the internet, and reference data on the device. A
      crossover study was carried out for 6 weeks in 2004, with the team having access
      to the personal digital assistant every alternate week. The primary outcome
      measure for assessing efficiency of communication was the length of time it took
      for clinicians to respond to a call. We also sought to assess the ease of
      adoption of new technology by evaluating the perceptions of the team (n = 9) to
      personal digital assistants, by administering a questionnaire. RESULTS: Doctors
      equipped with a personal digital assistant rather than a pager, responded more
      quickly to a call and had a lower of failure to respond rate (RR: 0.44; 95%CI
      0.20-0.93). Clinicians also found this technology easy to adopt as seen by a
      significant reduction in perceptions of nervousness to the technology over the
      six-week study period (mean (SD) week 1: 4.10 (SD 1.69) vs. mean (SD) week 6:
      2.20 (1.99); p = 0.04). CONCLUSION: The results of this pilot study show the
      possible effects of replacing the current hospital pager with a newer, more
      technologically advanced device, and suggest that a combined personal digital
      assistant and mobile phone device may improve communication between doctors. In
      the light of these encouraging preliminary findings, we propose a large-scale
      clinical trial of the use of these devices in facilitating inter-professional
      communication in a hospital setting.

PMID- 16109178
TI  - Cerebrospinal fluid signs of neuronal damage after antiretroviral treatment
      interruption in HIV-1 infection.
AB  - BACKGROUND: The neurofilament is a major structural component of myelinated
      axons. Increased cerebrospinal fluid (CSF) concentrations of the light chain of
      the neurofilament protein (NFL) can serve as a sensitive indicator of central
      nervous system (CNS) injury. To assess whether interrupting antiretroviral
      treatment of HIV infection might have a deleterious effect on the CNS, we
      measured NFL levels in HIV-infected subjects interrupting therapy. We identified
      subjects who had CSF HIV RNA concentrations below 50 copies/mL at the time
      combination antiretroviral therapy was interrupted, and for whom CSF samples were
      available before and after the interruption. RESULTS: A total of 8 subjects were
      studied. The median (range) CSF NFL level at baseline was <125 (<125-220) ng/L
      (normal <250 ng/L). All 8 subjects exhibited an increase in CSF and plasma HIV
      RNA after stopping therapy, accompanied by intrathecal immunoactivation as
      evidenced by CSF lymphocytic pleocytosis (7/8 patients) and increased CSF
      neopterin concentration (5/6 patients). Three subjects showed a consistent
      increase in CSF NFL, rising from <125 ng/L to a maximum of 880 (at day 148),
      1,010 (day 58) and 10,930 ng/L (day 101). None exhibited new neurological
      symptoms or signs, or experienced functional deterioration during the period off
      treatment; of 5 who underwent brief quantitative neurological testing, none
      showed worsening performance. CONCLUSION: These findings suggest that resurgence
      of active HIV replication may result in measurable, albeit subclinical, CNS
      injury. Further studies are needed to define the frequency and pathobiological
      importance of the increase in CSF NFL.

PMID- 16109179
TI  - Evidence that spontaneous reactivation of herpes virus does not occur in mice.
AB  - BACKGROUND: Some species, including humans and rabbits, exhibit periodic viral
      reactivation and shed infectious virus at the infected end organ. Mice may be an
      exception, because spontaneous shedding of infectious virus rarely, if ever,
      occurs. However, spontaneous molecular reactivation, i.e., the expression of a
      few viral genes and the synthesis of the viral glycoproteins coded for by these
      genes, has been reported. This finding has prompted the assumption that molecular
      reactivation is an indicator of reactivation and the production of infectious
      virus. The goal of this study was to differentiate between viral gene expression
      during latency and the episodic production of infectious virus in mice. RESULTS:
      Viral reactivation and infection were not seen in herpes simplex virus type 1
      (HSV-1) latent ganglion graft recipient BALB/c scid or immunocompetent BALB/c
      mice, which survived the 65-day observation period with no evidence of viral
      infection although the immunocompetent mice developed cellular and humoral
      immunity to HSV-1. In contrast, BALB/c scid recipients of ganglia containing
      reactivating virus invariably developed a local and, subsequently, systemic viral
      infection and died within 14 days. Immunocompetent BALB/c mice that received
      ganglion grafts containing reactivating virus survived the infection and became
      immune to the virus. Trigeminal ganglia removed from scid and immunocompetent
      recipient graft sites 5, 14, and 28 days after transplantation contained latent
      virus and viable neurons. CONCLUSION: The results suggest that, within the limits
      of detection of the experiments, spontaneous episodic production of immunogenic
      viral antigens but not of infectious virus occurs in mouse neural ganglia during
      latency.

PMID- 16109180
TI  - Genetic polymorphisms in DPF3 associated with risk of breast cancer and lymph
      node metastases.
AB  - BACKGROUND: Several studies have identified rare genetic variations responsible
      for many cases of familial breast cancer but their contribution to total breast
      cancer incidence is relatively small. More common genetic variations with low
      penetrance have been postulated to account for a higher proportion of the
      population risk of breast cancer. METHODS AND RESULTS: In an effort to identify
      genes that influence non-familial breast cancer risk, we tested over 25,000
      single nucleotide polymorphisms (SNPs) located within approximately 14,000 genes
      in a large-scale case-control study in 254 German women with breast cancer and
      268 age-matched women without malignant disease. We identified a marker on
      chromosome 14q24.3-q31.1 that was marginally associated with breast cancer status
      (OR = 1.5, P = 0.07). Genotypes for this SNP were also significantly associated
      with indicators of breast cancer severity, including presence of lymph node
      metastases (P = 0.006) and earlier age of onset (P = 0.01). The association with
      breast cancer status was replicated in two independent samples (OR = 1.35, P =
      0.05). High-density association fine mapping showed that the association spanned
      about 80 kb of the zinc-finger gene DPF3 (also known as CERD4). One SNP in intron
      1 was found to be more strongly associated with breast cancer status in all three
      sample collections (OR = 1.6, P = 0.003) as well as with increased lymph node
      metastases (P = 0.01) and tumor size (P = 0.01). CONCLUSION: Polymorphisms in the
      5' region of DPF3 were associated with increased risk of breast cancer
      development, lymph node metastases, age of onset, and tumor size in women of
      European ancestry. This large-scale association study suggests that genetic
      variation in DPF3 contributes to breast cancer susceptibility and severity.

PMID- 16109184
TI  - [Laparoscopic colonic surgery].

PMID- 16109181
TI  - PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double
      blind clinical trial [ISCRTN 74418480].
AB  - BACKGROUND: In patients with acute stroke, increased body temperature is
      associated with large lesion volumes, high case fatality, and poor functional
      outcome. A 1 degrees C increase in body temperature may double the odds of poor
      outcome. Two randomized double-blind clinical trials in patients with acute
      ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen
      (paracetamol) results in a small but rapid and potentially worthwhile reduction
      of 0.3 degrees C (95% CI: 0.1-0.5) in body temperature. We set out to test the
      hypothesis that early antipyretic therapy reduces the risk of death or dependency
      in patients with acute stroke, even if they are normothermic. METHODS/DESIGN:
      Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind
      clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients.
      Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and
      the possibility to start treatment within 12 hours from onset of symptoms. The
      study will have a power of 86% to detect an absolute difference of 6% in the risk
      of death or dependency at three months, and a power of 72% to detect an absolute
      difference of 5%, at a 5% significance level. DISCUSSION: This is a simple trial,
      with a drug that only has a small effect on body temperature in normothermic
      patients. However, when lowering body temperature with acetaminophen does have
      the expected effectiveness, 20 patients will have to be treated to prevent
      dependency or death in one.

PMID- 16109185
TI  - [Venous thrombosis prophylaxis in the departments of internal medicine--neglected
      -increases focus is necessary].

PMID- 16109186
TI  - [Autoimmune thrombophilia].
AB  - Antibodies against phospholipids and phospholipid-binding proteins, especially
      anti-cardiolipin and anti-beta2-glycoprotein I antibodies, are important
      diagnostic markers of autoimmune thrombophilia. These autoantibodies are quite
      common among patients with systemic lupus erythematosus but can also be found in
      individuals without concurrent rheumatic conditions. Apart from thromboembolic
      disease, these antibodies are linked to recurring fetal loss and intrauterine
      fetal death. In patients with recurring thrombotic events in whom anti
      phospholipid antibodies or prolonged aPTT (as a sign of lupus anticoagulant
      activity) is found, long-term or even lifelong anticoagulation therapy should be
      considered. Habitual spontaneous abortions and other obstetric complications are
      often preventable with LMW heparin in combination with low-dose acetylsalicylic
      acid. In this review, we outline a diagnostic strategy for uncovering autoimmune
      thrombophilia supplemented with functional and genetic tests for
      hypercoagulability.

PMID- 16109187
TI  - [The relationship between the placebo effect and spontaneous improvement in
      research on antidepressants. Are placebos powerless?].
AB  - Clinical trials of antidepressant medications have generally found large changes
      in groups given a placebo, which may be due to either spontaneous remission or a
      true placebo effect. This paper reviews the evidence for a true placebo effect in
      the treatment of unipolar depressed outpatients. Although there is no evidence
      from experimental studies, a rather substantial amount of circumstantial evidence
      indicates a true placebo effect. This article raises the question of whether it
      is meaningful to require experimental evidence for a loose and unspecified
      concept involving varying components such as placebo.

PMID- 16109188
TI  - [Endoscopic treatment of gastroesophageal reflux disease].
AB  - Gastroesophageal reflux disease (GERD) is highly prevalent in the general
      population, and the treatment is mostly medical. However, lifelong therapy with
      proton pump inhibitors is expensive, and some patients with GERD have surgery
      because of unsatisfying symptom control, poor compliance or lack of acceptance of
      lifelong medical therapy. In the last couple of years, four endoscopic treatment
      options for GERD have evolved. These are endoscopic suturing, gastroplication,
      local radiofrequency treatment and injection of biopolymer into the
      gastroesophageal junction. The results so far have been promising regarding
      symptomatic control and patient satisfaction. The lack of normalized pH in the
      lower esophagus, however, and the lack of a physiological background for the
      impressing symptomatic effect, plus the fact that there has been only one sham
      controlled randomized clinical trial, suggest that carefulness should be
      exercised in utilizing the procedures until more solid evidence is available. The
      methods in themselves are promising, though, and will probably have a natural
      position in the future treatment of GERD.

PMID- 16109189
TI  - [Prevention of neural tube defects with periconceptional folic acid
      supplementation in Europe].
AB  - The conclusion of a report recently published by EUROCAT is that the potential
      for preventing neural tube defects with periconceptional folic acid
      supplementation is still far from being fulfilled in Europe. A number of
      recommendations to increase periconceptional folate status are made. In Denmark
      less than 20% of pregnant women follow the official recommendations on
      periconceptional folic acid supplementation, making the conclusions of the
      EUROCAT report relevant.

PMID- 16109190
TI  - [Maternal diabetes and congenital malformations].
AB  - Maternal diabetes is a known risk factor for congenital malformations. Maternal
      hyperglycemia is a non-specific teratogen. The risk of congenital malformations,
      even with optimal metabolic control, is considerably elevated compared with non
      diabetic pregnancies. The relationship between maternal hyperglycemia in early
      pregnancy and the risk of congenital malformations seems to be linear without any
      threshold level. To diminish the risk of congenital malformations, close
      preconceptional and first-trimester diabetic control and folic acid
      supplementation of 5 mg/day are recommended.

PMID- 16109191
TI  - [Laparoscopic appendectomy].
AB  - Laparoscopic appendectomy is an effective, safe procedure for the treatment of
      patients with acute appendicitis. Studies have demonstrated the diagnostic and
      therapeutic advantages of the method and its positive impact on laparoscopic
      training. However, the procedure has not been widely accepted in Denmark. This
      paper describes the technical and educational aspects of laparoscopic
      appendectomy and provides practical information on the implementation of the
      procedure in daily practice.

PMID- 16109192
TI  - [Laparoscopy-assisted colon resection. A prospective study with short-term
      results and 12-38 months' follow-up].
AB  - INTRODUCTION: Despite several reports demonstrating its clinical benefits,
      laparoscopy-assisted colectomy (LAC) has not gained universal acceptance because
      of its oncologic implications. In this article we present our experiences with
      LAC. MATERIALS AND METHODS: A consecutive series of 75 patients undergoing LAC
      between February 2001 and March 2003 was followed. Fifty-nine of the patients had
      colon cancer. Standardized postoperative care procedures were used. The median
      follow-up time for the colon cancer patients was 19 months (range 12-38 months).
      RESULTS: The median operation time was 190 minutes (range 150-300 minutes). Two
      patients (3%) required a conversion to laparotomy. Ten patients (13%) suffered
      from postoperative complications. The postoperative mortality rate was 3%. The
      median length of stay for the patients who were directly discharged to their home
      was 4 days (range 1-30 days). There were no readmissions in the postoperative
      period. Fifty-five patients with malignancy underwent curative resection, while
      four, who had metastatic disease, were operated on for palliation. The frequency
      of recurrence and the cancer-related mortality rate in the follow-up period were
      both 21%. No significant differences were found between patients with Dukes' type
      B and type C with regard to being free of recurrence or cancer-related survival.
      One port-site recurrence (2%) occurred in the patients who underwent curative
      resection. DISCUSSION: Our results shows that LAS has clinical advantages,
      especially in the short term, and provides better oncologic results than open
      surgery, especially in cases of Dukes' type C cancer. LAC for cancer should be
      performed by experienced hands and monitored adequately by a national register to
      ensure satisfactory oncologic outcomes.

PMID- 16109193
TI  - [Localization of colonic tumor in laparoscopic surgery. Intraoperative
      colonoscopy or preoperative tattoo].
AB  - INTRODUCTION: Tumor localization may be critical in laparoscopic surgery because
      manual palpation may not be possible. This study focused on the need for
      intraoperative colonoscopy to identify the tumor site. We also present our
      preliminary experiences with preoperative tattoo of the resection site. MATERIALS
      AND METHODS: A prospective, consecutive, consecutive study of 61 patients
      operated on laparoscopically for colonic tumor together with 9 patients with
      preoperative tattoo of the resection site (5 laparoscopic and 4 open operations)
      was done. RESULTS: Intraoperative colonoscopy was necessary to identify the tumor
      site in 23% of the 61 patients without preoperative tattoo. Tumor grading and
      localization in this group did not differ from that in the group where
      colonoscopy was not needed (p>0.05). The median operation time was significantly
      longer in the group in which intraoperative endoscopy was performed (p<0.05). The
      preoperative tattoo caused no complications, and the tattoo was visible in all 9
      patients intraoperatively. DISCUSSION: Almost one fourth of the patients operated
      on laparoscopically for colonic tumor needed intraoperative colonoscopy to
      identify the tumor site. This impeded the laparoscopic operation, prolonged the
      operation time and increased the potential risk for infectious complications.
      Preoperative tattoo, which renders intraoperative colonoscopy superfluous, should
      therefore be considered for all patients operated on laparoscopically for colonic
      tumor, as it is difficult to determine in advance the patients in whom the tumor
      site will be hard to identify intraoperatively.

PMID- 16109194
TI  - [The use of venous thromboprophylaxis in Danish medical departments. A
      questionnaire survey].
AB  - INTRODUCTION: Our goal was to investigate the use of venous thromboprophylaxis in
      Danish hospital departments of internal medicine, neurology and intensive care.
      MATERIALS AND METHODS: All 242 Danish departments/wards received a two-page
      survey form to complete. Two reminders were sent. RESULTS: Eighty-two percent
      responded. Ninety percent use thromboprophylaxis, but only 69% of intensive care
      wards, 36% of neurological wards, and 22% of internal medicine wards have
      established general guidelines for its use. There is no difference between
      hospitals in larger cities and those in smaller cities. The most usual indication
      was prolonged bed rest. DISCUSSION: Compared with the scientific documentation,
      the use of thromboprophylaxis in Danish medical wards must be considered
      insufficient.

PMID- 16109195
TI  - [Structured documentation of patients' medical records. A new record structure
      for emergency admissions is coming].
AB  - INTRODUCTION: In recent years a range of efforts to shorten the length of stay
      (LOS) for patients admitted to hospitals has been tested. Some studies indicate
      that this might be accomplished by rigorous planning of patient pathways and
      structured documentation of medical records. In this study the effect of a
      structured case record model was tested. METHODS: The new record structure was
      developed using predefined requirements for content, placement and presentation
      of documentation. Instruction of staff was followed by a switch to the new model
      from one day to the next. Collection of data was carried out three months before
      and five to eight months after implementation of the model. RESULTS: The
      department succeeded in including well over 50% of all includable patients.
      However, the analysis encompassed all includable patients (''intention to treat''
      principle). The number of cases analysed was 340 before and 353 after
      implementation of the model. Average LOS was reduced by 1.1 day from before
      implementation to after implementation. This was not statistically significant.
      However, the model was subsequently kept in use by the department. DISCUSSION:
      This pilot study shows a non-significant tendency to shotening of LOS by using a
      structured case record model. It is important to pay attention to the practical
      difficulties of implementing new documentation tools.

PMID- 16109196
TI  - [A new, empirically established hypochondriasis diagnosis--secondary
      publication].
AB  - The narrow ICD-10 and DSM-IV definition of hypochondriasis makes it a rarely used
      diagnosis. Based on a latent class analysis of the symptoms exhibited by 701
      patients (ages 18-65) in general practice, a new and more valid hypochondriasis
      diagnosis was defined in this study. The main symptom is "obsessive rumination
      about illnesses", and the patient must also have at least one of five other
      symptoms. The prevalence was 9.5 for both genders. There was a good agreement
      between the diagnoses made during the psychiatric interview and the physicians'
      assessments.

PMID- 16109197
TI  - [Organoid nevus (nevus sebaceus) dominated by the apocrine glands].
AB  - We report a case of congenital organoid nevus with an excessive number of
      apocrine glands. A one-year-old boy presented with a slowly enlarging keratotic
      element in the left temporal region, and biopsy showed hyperkeratosis,
      acanthosis, follicular plugging and multiple transverse sections of mature
      apocrine glands filling the reticular dermis. The lesion was benign and treatment
      was therefore conservative. In rare cases, various types of adnexal neoplasms may
      develop, but malignant tumours occur very seldom.

PMID- 16109198
TI  - [Ischemic cerebral infarction in a young woman undergoing gonadotropin treatment
      for infertility].
AB  - We describe a case of a 27-year-old previously healthy woman with a homonymous
      hemianopsia caused by thrombosis of a branch of the posterior cerebral artery.
      The woman had been treated with gonadotropin due to infertility and gone through
      in vitro fertilisation before the symptoms started. She was pregnant in the first
      trimester when we first saw her. We did not find any predisposing factors, and
      the clinical examination, including biochemical analysis, MRI arteriography and
      echocardiography, did not reveal any cause for the cerebral infarction (CI). The
      risk of CI during pregnancy itself is less than among non-pregnant women (0, 7)
      but increases in the postpartum period (8, 7). The cause of cerebral infarction
      in this case was idiopathic, but we must be aware of the possible link between
      treatment with gonadotropin for infertility and the development of cerebral
      infarction.

PMID- 16109199
TI  - [Activation of psoriasis in patients undergoing treatment with interferon-beta].
AB  - Psoriasis is a chronic, inflammatory skin disorder that is induced and aggravated
      by a number of endogenous and exogenous factors. Traditionally lithium, beta
      blockers, NSAIDs, ACE inhibitors and antimalarials have been associated with
      psoriasis, but interferon can also be a triggering factor. We present two
      patients with multiple sclerosis who suffered from activation of psoriasis in
      relation to interferon-beta treatment. In one of the patients, psoriasiform
      injection site lesions persisted six years after termination of the interferon
      treatment.

PMID- 16109200
TI  - [A possible successor of the Mantoux test after 97 years].

PMID- 16109210
TI  - [Stickwalking--a new public sport].

PMID- 16109211
TI  - [Do fish and omega-3 fatty acid prevent heart disease?].

PMID- 16109215
TI  - [Independent clinical intervention research--or evidence-biased medicine?].

PMID- 16109217
TI  - [Alternative treatment of migraine].

PMID- 16109219
TI  - [Dipyridamole infusion in chronic obstructive pulmonary disease].

PMID- 16109220
TI  - [Classification of surgical procedures, 2nd edition].

PMID- 16109221
TI  - [Infliximab treatment of peristomal pyoderma gangrenosum in ulcerative colitis].

PMID- 16109223
TI  - [Follow up of a contribution about treatment of acute apoplexy].

PMID- 16109225
TI  - [Paragraph 9 in the Ethical Rules and soap-pump eczema on the back of the hand].

PMID- 16109239
TI  - [Paradigmatic shift in drug treatment of Crohn disease].

PMID- 16109240
TI  - [Mesalazine for maintenance of medically-induced remission in Crohn disease: a
      survey of a Cochrane review].

PMID- 16109241
TI  - [Measures for the performance of diagnostic tests].
AB  - Systematic reviews have revealed that the methodological quality of studies on
      diagnostic accuracy is mediocre. In addition, clinicians may experience
      difficulties in interpreting and using measures describing the accuracy of a
      test. Using the Ottawa Ankle Rule as an example, we review the measures commonly
      used to describe the accuracy of diagnostic tests. The performance of tests is
      often given in terms of sensitivity and specificity. However, these measures have
      no relevance to clinicians unless they can be converted into predictive values.
      We describe how to calculate the predictive values and how they can be determined
      using likelihood ratios and Fagan's nomogram. The reader is introduced to the
      critical appraisal of results based on studies of the accuracy of tests. We
      describe how both the clinical spectrum and the methodological quality can
      influence estimates of diagnostic accuracy and stress the inevitable uncertainty
      involved in extrapolating results from the literature to clinical practice.
      Methods of calculating the confidence intervals for estimates of accuracy are
      presented.

PMID- 16109242
TI  - [Avocado/soybean unsaponifiables in the treatment of knee and hip
      osteoarthritis].
AB  - Avocado/soybean unsaponifiables (ASU) is an extract prepared from avocado and
      soybean oil. The product has been approved as a prescription drug in France for
      several years and has now been introduced in Denmark as a food supplement. ASU
      has been examined in vitro and in animal studies that have showed an anti
      inflammatory effect and a stimulatory effect on proteoglycan synthesis in
      chondrocytes. Four randomized, double-blind, placebo-controlled clinical trials
      have been published. These studies indicate that ASU has an effect on the
      symptoms of knee and hip osteoarthritis but not on the structural changes caused
      by osteoarthritis.

PMID- 16109243
TI  - [Microglia--biology and relevance to disease].
AB  - Microglia, the resting macrophage population in the brain and spinal cord, has a
      central role in inflammatory processes and in acute and chronic degenerative
      diseases of the central nervous system. The possibility of utilizing microglia
      diagnostically has emerged with the prospect of visualization of reactive
      microgliosis via positron emission tomography. Microglia might also have a
      therapeutic potential by way of recruitment of microglial precursors from the
      blood with the opportunity to introduce genetically modified cells lesion
      specifically into the central nervous system via the bloodstream. Knowledge about
      microglial function has preferentially been obtained via studies in experimental
      animal models of the pathological central nervous system. In spite of the rather
      extensive knowledge regarding the pathophysiological implications of these cells,
      their function in the normal central nervous system remains rather unknown.

PMID- 16109244
TI  - [Treatment and prevention of restenosis after percutaneous coronary intervention.
      Balloons, stents, radioactive rays and drug-releasing stents].
AB  - This article briefly reviews the causes of restenosis and the current strategies
      for preventing and treating restenosis after percutaneous coronary intervention.
      Interventions such as intracoronary radiation and drug-eluting stents are
      discussed.

PMID- 16109245
TI  - [Beta-radiation as adjuvant treatment of in-stent restenosis in coronary
      vessels].
AB  - INTRODUCTION: The purpose of this study was to describe our initial "real-world"
      experience with vascular b-radiation for in-stent restenosis using a simple
      angioplasty approach without stent implantation. MATERIALS AND METHODS: Thirty
      five consecutive patients with in-stent restenosis were treated with balloon
      angioplasty (n = 28), cutting balloon angioplasty (n = 3), or angioplasty plus
      stent implantation (only in case of significant dissection: n = 4), followed by
      catheter-based beta-radiation. Angiographic follow-up was performed after 6 to 10
      months. RESULTS: One patient experienced a left main stem occlusion immediately
      after beta-radiation, which necessitated an acute coronary bypass operation. No
      other complications related to the radiation procedure were observed. In-stent
      restenosis recurred in 6 of the 34 patients (18%). DISCUSSION: Our results
      indicate that catheter-based radiation can be safely introduced at centres
      without previous experience with this treatment modality. Furthermore, the in
      stent restenosis recurrence rates after catheter-based radiation which have been
      obtained in randomised trials can be reproduced in consecutive patients.

PMID- 16109246
TI  - [Primary percutanous intervention in acute mycardial infarction. A comparison
      with the DANAMI-2 results].
AB  - INTRODUCTION: Several studies, including the DANAMI-2 trial, have shown that
      primary percutanous intervention (PCI) results in better survival, fewer
      reinfarctions and fewer cerebrovascular incidents than thrombolysis in the
      treatment of acute ST-elevation myocardial infarction (STEMI). The aim of this
      study was to follow the implementation of primary PCI as a routine treatment for
      patients with STEMI and to compare the results with those of DANAMI-2. MATERIALS
      AND METHODS: We performed a prospective analysis of 212 patients admitted to our
      department from 1 April 2002 to 31 December 2002 with STEMI. Acute coronary
      angiography and, if indicated, primary PCI were performed. RESULTS: At 30 days,
      the mortality rate was 6.6%, the reinfarction rate 1.4% and the rate of disabling
      stroke 1.4%. Combined endpoints were present in 8% of the patients. The results
      are in agreement with those from the DANAMI-2 trial. DISCUSSION: Primary PCI can
      be performed in daily clinical practice in accordance with the DANAMI-2 protocol.
      The results are in agreement with data from newly published meta-analyses.

PMID- 16109247
TI  - [A year"s experience with primary percutaneous intervention as the standard
      treatment of patients with ST-elevation infarction in the County of North
      Jutland].
AB  - INTRODUCTION: Primary percutaneous intervention (PCI) became the standard
      treatment of patients with ST-elevation infarction in the hospitals in the County
      of North Jutland in May 2002, according to a protocol that was slightly modified
      from that used in the DANAMI-2 study: A cumulated ST elevation of 2 mm was
      required, versus 4 mm in the DANAMI-2 study; the ECG analyses were performed
      centrally after transmission of the ECGs to a mobile fax at the PCI centre; and
      in selected cases the intervention technique was supplemented with thrombectomy.
      The purpose of this study was to assess whether primary PCI in clinical practice
      with these modifications gave satisfactory results compared to the invasive arm
      of the DANAMI-2 study. MATERIALS AND METHODS: The study comprised all patients
      who underwent acute coronary angiography due to ST-elevation infarction in the
      Department of Cardiology, Aalborg Hospital, from 1 May 2002 to 30 April 2003. The
      patients were admitted to the nearest hospital and transferred to the PCI centre
      for acute intervention. RESULTS: The study comprised 297 patients. In transported
      as well as non-transported patients, the median times from onset of symptoms to
      invasive treatment in the Aalborg material were a few minutes shorter than in the
      DANAMI-2 study. PCI treatment was performed in 266 patients (90%), of whom 247
      (93%) had a stent implanted, as had been done in the DANAMI-2 study. TIMI III
      flow was achieved in 94% of the cases versus 89% in the DANAMI-2 study. In the
      patients who underwent PCI treatment, the mortality rates after 30 days were 4.0%
      and 5.4%, respectively. DISCUSSION: This study showed that it was possible to
      implement primary PCI in clinical practice with results better than those
      attained by fibrinolysis. Consequently, primary PCI should continue to be the
      preferred reperfusion treatment of ST-elevation infarction.

PMID- 16109249
TI  - [Gastric resection for cancer in Denmark, 1999-2004].
AB  - INTRODUCTION: We evaluated the organisation, management and outcome for patients
      operated on with gastric resection for cancer in Denmark in the period 1999-2003.
      MATERIALS AND METHODS: Nationwide data based on the National Patient Registry and
      discharge information from hospital departments in the period 1 January 1999 to
      31 December 2003 were analysed. RESULTS: Thirty-seven departments performed 537
      resections, with an average of 20 departments per year performing such
      operations. Five departments performed 57.2% of the operations, while 20
      departments performed 10.2%. The average postoperative stay was 18 days and the
      hospital mortality rate was 8.2%, equally distributed with 7.8% for Billroth II
      resections and 8.5% for total gastrectomy. DISCUSSION: The organization of
      gastric cancer surgery in Denmark in 1999-2003 was not optimal, with about 20
      departments performing about 100 gastric resections annually, and with a
      mortality rate of slightly over 8% and an average hospital stay of 18 days. We
      propose that in future, gastric resections for cancer should be performed in a
      maximum of five departments nationwide.

PMID- 16109248
TI  - [Smoking cessation among patients with acute heart disease. A randomised
      intervention project].
AB  - INTRODUCTION: Our goal was to investigate whether ambulatory smoking cessation
      among patients in a cardiologic department would (1) reduce the number of smokers
      by at least 25% after 12 months compared to a control group and (2) influence
      whether the individual patient was readmitted to hospital. We used a randomised,
      controlled, prospective intervention project design. MATERIALS AND METHODS:
      Everyone hospitalised during the project period was screened. Those who fulfilled
      the criteria for inclusion were randomised for inclusion in either the
      intervention group or the control group. Both groups were given the department's
      smoking cessation information. In addition, the intervention group attended five
      ambulatory smoking cessation intervention sessions. Each patient's smoking status
      was registered after 12 months. chi2-test and logistic regression analysis were
      used to test differences, associations and control of confounders. RESULTS: In
      all, 3,982 patients were screened, 29.5% of whom were smokers. The study included
      105 patients: 54 in the intervention group and 51 in the control group. After 12
      months, 52% of those in the intervention group compared to 39% in the control
      group had become non-smokers, which was non-significant (p = 0,14). Ischemic
      heart disease (IHS) was significantly associated with smoking cessation. After
      adjustment for this confounder, the result was enhanced (p = 0,06). Readmission
      to hospital was not affected by smoking cessation (p = 0,73). DISCUSSION:
      Ambulatory smoking cessation intervention had no significant effect on smoking
      cessation on an unselected group of patients in a cardiologic hospital
      department. The project does indicate that ambulatory smoking cessation
      interventions could have an effect on patients with IHS.

PMID- 16109251
TI  - [Ginseng modulates the immune response via its effect on cytokine production-
      secondary publication].
AB  - Ginseng has been shown to modulate the immune system. In this study, ginseng"s
      effects against chronic P. aeruginosa lung infection in animal models and its
      cytokine-modulating effects on leukocytes were investigated. Leukocytes cultured
      with ginseng produced more interleukin-12. Animal models treated with ginseng
      s.c. showed a much faster bacterial clearance, milder lung pathology, activation
      of phagocytes and a Th1 immune response. These results suggest that ginseng
      treatment induced a Th1-like immune response, which improved the pathologic
      course in our animal models.

PMID- 16109250
TI  - [Neurological late sequelae in twins born after in vitro fertilisation--secondary
      publication. A national cohort study].
AB  - Currently 4% of the Danish national birth cohort is born after in vitro
      fertilisation techniques and almost 40% of these children are twins. In this
      register-based national cohort study, twins from assisted conception (n = 3393)
      had a similar risk of neurological sequelae and cerebral palsy as their naturally
      conceived peers (n = 10.239) and assisted conceived singletons (n = 5130).
      Further children born after intracytoplasmic sperm injection (ICSI) had the same
      risk of neurological sequelae as children born after conventional IVF.

PMID- 16109252
TI  - [Closure of abdominal wall incision].

PMID- 16109253
TI  - [Wandering spleen].
AB  - The spleen is well fixed below the left side of the diaphragm. Wandering spleen
      is a rare condition of unknown pathogenesis. The wandering spleen is most often
      localized in the lower abdomen or pelvis. The diagnosis may be difficult if
      wandering spleen is not suspected. Often a wandering spleen can be palpated in
      the lower abdomen. In the rare cases of torsion of the splenic vascular pedicle,
      wandering spleen becomes symptomatic, and splenectomy should be performed. We
      report a case of a 20-year-old female treated with splenectomy because of torsion
      of the vascular pedicle.

PMID- 16109254
TI  - [Dynamic ECG changes as a result of Brugada syndrome, an overlooked diagnosis?].
AB  - Brugada syndrome is a primary electrical disease involving a wide spectrum of
      phenotypes. The hallmark of Brugada syndrome is the ST elevation in leads V1 to
      V3. We present three cases of Brugada syndrome. The first patient was diagnosed
      via routine ECG and a programmed electric stimulation. The second patient was
      mistakenly diagnosed as having a right coronary occlusion. The last patient had
      been resuscitated before admittance and received an implantable cardioverter
      defibrillator. Treatment of patients with Brugada syndrome is limited by the lack
      of reliable indicators of risk.

PMID- 16109255
TI  - [100 years of hormones: the physiologist Ernest H. Starling's introduction of the
      hormone concept and the missing Nobel Prize].
AB  - The term hormone is by now familiar to all, but it is the English physiologist
      and physician Ernest H. Starling's term, and before him the search made little
      sense even in the light of "internal secretion". He saw the great potential of
      regulatory physiology through chemical coordination of the bodily functions by
      the circulating blood. Throughout his life he stressed fundamental scientific
      attitudes and ideas with remarkable persistence and power, and hormones have
      stood the test of time. Sadly, he never received a Nobel Prize in Physiology or
      Medicine.

PMID- 16109256
TI  - [Clopidogrel and upper gastrointestinal hemorrhage].

PMID- 16109260
TI  - [Thrombosis prophylaxis and rational pharmacotherapy].

PMID- 16109264
TI  - [Electromyography and diagnosis of muscular diseases].

PMID- 16109265
TI  - [The Medical Products Agency and testosterone treatment. The 3rd and the last
      act].

PMID- 16109266
TI  - [Is gamma globulin obsolete in the prevention of infectious liver diseases?].

PMID- 16109268
TI  - [Recovery: a pseudoconcept or a symbolic reality in a paradigmatic shift?].

PMID- 16109269
TI  - [Same requirements for private hospitals?].

PMID- 16109271
TI  - [Erythema infectiosum 2].

PMID- 16109272
TI  - [Private hospitals--facts and prejudice].

PMID- 16109275
TI  - [Bariatrics].

PMID- 16109274
TI  - [Reply to Troels Kardel's article "Can a physician pay too many visits"?
      Ugeskrift for Laeger nr 24].

PMID- 16109286
TI  - The importance of examining blood pressure reactivity and recovery in anger
      provocation research.
AB  - OBJECTIVE: We investigated the moderating relationship of hostility on emotional
      and physiological arousal due to acute anger provocation; stress reactivity and
      recovery were measured. METHOD: Forty-five participants completed a measure of
      trait hostility (CMHQ) and performed a mental arithmetic (serial 7s) task while
      receiving scripted comments at set intervals designed to provoke anger
      (harassment). The impact of trait hostility (high, medium or low) on arousal and
      recovery was examined. RESULTS: Participants low in self-reported hostility
      showed greater HR reactivity to the task but recovered quickly. Participants high
      in hostility showed noticeably slower recovery in SBP maintained after task
      completion. CONCLUSIONS: The findings underscore the importance of examining both
      reactivity and recovery data in anger provocation research because the apparent
      influence of trait hostility on cardiovascular functioning would have been missed
      if recovery had not been systematically studied.

PMID- 16109287
TI  - Neural evidence of effects of emotional valence on word recognition.
AB  - There are no clear reports of electrophysiological evidence of the facilitating
      effect of negative valence on word recognition. However, behavioral psychological
      studies have suggested that negative words can be recognized more accurately than
      positive and neutral words. This study aimed to examine whether, and if so how,
      the valence of words could influence accuracy and event-related potentials (ERPs)
      in a recognition task. ERPs were recorded from 20 healthy subjects during
      performance of a word recognition task. We found a behavioral advantage in
      discriminability between old and new items for negative words. As for ERPs, the
      positive-going shift was evident for correct responses to targets in late latency
      at midline and left centro-parietal sites. Additionally, the magnitude of this
      component was greatest for negative targets, next for positive targets, and least
      for neutral targets. The findings offer support for the idea that negative
      content greatly accelerates recognition memory compared to positive and neutral
      words.

PMID- 16109288
TI  - Anxiety and synchrony of alpha oscillations.
AB  - The associations between state anxiety and individually adjusted alpha sub-bands
      mean spectral power and coherence measures registered in resting condition and
      during experimental settings were investigated in 30 males aged 18-25 years.
      Averaged across all cortical sites, spectral power was treated as a complex
      measure dependent on both the number of active alpha oscillators and the degree
      of their synchrony. Averaged across all electrode pairs, squared coherence was
      treated as a global measure of alpha synchrony. The relationship between state
      anxiety and baseline alpha power was mostly mediated by alpha synchrony. During
      transition through experimental settings, the dynamics of alpha2 and alpha3 power
      was mostly accounted for by changes of these sub-bands' synchrony. The synchrony
      independent power component demonstrated linear trends implying that, during the
      experiment, the number of active alpha oscillators linearly decreased in subjects
      with low state anxiety and linearly increased in subjects with high state
      anxiety. These findings are discussed in terms of alpha synchronization as an
      active process, allowing dynamic regulation of alpha system preparedness for
      processing of external stimuli.

PMID- 16109289
TI  - Sex differentiated responses to intranasal trigeminal stimuli.
AB  - The aim of the study was to address sex-related hemispheric differences in
      trigeminal event-related potentials while controlling for the subjects' olfactory
      sensitivity. Event-related potentials to lateralized stimulation using the
      trigeminal stimulant CO(2) were recorded in 28 healthy young subjects (16 women).
      There was no sex-related difference in olfactory sensitivity. Results indicated a
      sex-differentiated response to trigeminally induced pain. Women were found to
      have generally higher amplitudes and shorter latencies of the late positive
      component than men. Moreover, men and women exhibited different hemispheric
      activations in that women expressed shorter latencies over the left hemisphere
      than men. The pronounced sex-related difference of the late positive component
      suggests a cognitive/emotional impact on the processing of intranasal pain as
      indicated by others.

PMID- 16109290
TI  - Visually evoked phase synchronization changes of alpha rhythm in migraine:
      correlations with clinical features.
AB  - OBJECTIVE: This study aimed to compute phase synchronization of the alpha band
      from a multichannel electroencephalogram (EEG) recorded under repetitive flash
      stimulation from migraine patients without aura. This allowed examination of
      ongoing EEG activity during visual stimulation in the pain-free phase of
      migraine. METHODS: Flash stimuli at frequencies of 3, 6, 9, 12, 15, 18, 21, 24,
      and 27 Hz were delivered to 15 migraine patients without aura and 15 controls,
      with the EEG recorded from 18 scalp electrodes, referred to the linked earlobes.
      The EEG signals were filtered in the alpha (7.5-13 Hz) band. For all stimulus
      frequencies that we evaluated, the phase synchronization index was based on the
      Hilbert transformation. RESULTS: Phase synchronization separated the patients and
      controls for the 9, 24 and 27 Hz stimulus frequencies; hyper phase
      synchronization was observed in patients, whereas healthy subjects were
      characterized by a reduced phase synchronization. These differences were found in
      all regions of the scalp. CONCLUSIONS: During migraine, the brain synchronizes to
      the idling rhythm of the visual areas under certain photic stimulations; in
      normal subjects however, brain regions involved in the processing of sensory
      information demonstrate desynchronized activity. Hypersynchronization of the
      alpha rhythm may suggest a state of cortical hypoexcitability during the
      interictal phase of migraine. SIGNIFICANCE: The employment of non-linear EEG
      analysis may identify subtle functional changes in the migraine brain.

PMID- 16109291
TI  - Mental and physical effort affect vigilance differently.
AB  - Both physical and mental effort are thought to affect vigilance. Mental effort is
      known for its vigilance declining effects, but the effects of physical effort are
      less clear. This study investigated whether these two forms of effort affect the
      EEG and subjective alertness differently. Participants performed a physical task
      and were subsequently presented with a mental task, or vice versa. Mental effort
      decreased subjective alertness and increased theta power in the EEG. Both results
      suggest a vigilance decline. Physical effort, however, increased subjective
      alertness and alpha and beta1 power in the EEG. These findings point towards an
      increase in vigilance. Beta2 power was reduced after physical effort, which may
      reflect a decrease in active cognitive processing. No transfer effects were found
      between the effort conditions, suggesting that the effects of mental and physical
      effort are distinct. It is concluded that mental effort decreases vigilance,
      whereas physical effort increases vigilance without improving subsequent task
      performance.

PMID- 16109292
TI  - Time.

PMID- 16109293
TI  - The regulatory influence on medication administration in long-term care
      facilities.

PMID- 16109294
TI  - Meeting nutrition needs in long-term care.

PMID- 16109295
TI  - Resiliency: a factor to consider when facilitating the transition from hospital
      to home in older adults.

PMID- 16109296
TI  - Long-term care insurance: buy it or not!
AB  - Subscribing to a long-term care (LTC) insurance plan for future health care and
      services is one of the most difficult decisions aging Americans need to make
      today. Although it may be difficult to predict who will need an LTC plan and for
      how long, various factors play an important role in determining whether to
      purchase LTC insurance. This article provides general information about LTC plans
      including private insurance, their coverage, and implications for gerontologic
      nurses.

PMID- 16109297
TI  - A nurse goes shopping for a continuing care retirement community.
AB  - The selection of a continuing care retirement community (CCRC) in which to live
      is not a matter of flipping a coin. It involves serious and time-consuming
      investigation. For most people, it is a daunting task. Elderly people who decide
      on a CCRC for their living arrangement need to follow a selection process to
      arrive at the appropriate choice--the choice that best meets their particular
      needs and provides quality of life. This personal account gives insight into one
      person's experience with the process. Nurses who are knowledgeable about the
      types of CCRCs available are in a position to help their patients make more
      informed choices.

PMID- 16109298
TI  - Urinary tract infections in the elderly: a survey of physicians and nurses.
AB  - The purpose of this study was to identify, in the presence of significant
      bacteriuria, the symptoms that determine and conditions that affect whether a
      physician will begin antibiotic treatment in the elderly; 2 physician groups were
      studied: geriatric physicians and family practice/internal medicine physicians.
      We also sought to compare these results to symptoms and conditions that determine
      nurses' decisions to begin assessment for urinary tract infections (UTIs) in this
      population. We also sought to determine the importance these 3 groups placed of
      monitoring asymptomatic bacteriuria for specific elderly patient populations.
      Quantitative questionnaires were sent to a convenience sample of 1900 physicians
      and nurses. Sixty-eight of the 300 geriatric physicians (23%), 113 of the 1000
      family practice or internal medicine physicians (11%), and 192 of the 600 nurses
      (32%) returned surveys. Results showed differences between physician groups and
      nurses concerning whether cloudy and malodorous urine were symptoms of a UTI.
      This survey also found that physicians consider patient conditions to a greater
      extent than nurses do in their decisions regarding UTIs. Geriatric physicians
      appear to be less likely to monitor asymptomatic bacteriuria in any elderly
      patient population. Finally, we found that with regard to monitoring asymptomatic
      bacteriuria, both physician groups and the nurse group gave the greatest support
      for monitoring among elderly who have difficulty presenting symptoms of a UTI.

PMID- 16109299
TI  - Chronic pain in the elderly: a continuing education program for certified nursing
      assistants.
AB  - One of the greatest challenges facing nursing today is the provision of proper
      pain management in patients suffering from both acute and chronic pain. The
      purpose of this article is to provide an introduction to a continuing education
      program for use by registered nurse instructors in teaching certified nursing
      assistants (CNAs) about their role in the management of pain in elderly persons.
      The article includes a summary of the program content.

PMID- 16109300
TI  - Staff perceptions concerning barriers and facilitators to end-of-life care in the
      nursing home.
AB  - Although many nursing home residents have chronic, life-limiting conditions, most
      die without the benefit of palliative care or with palliation delayed until the
      last days of life. The goal of this study was to determine whether the presence
      of a comprehensive palliative care program in nursing homes would affect the
      knowledge and attitudes of the staff. The intervention group was able to identify
      more problems in delivering palliative care than the control group, but this only
      reached statistical significance on 2 items. Nevertheless, the current study
      suggests that the presence of a palliative care program within a nursing home
      does increase general knowledge of the problems faced in caring for the dying.

PMID- 16109301
TI  - Apigenin decreases hemin-mediated heme oxygenase-1 induction.
AB  - Hemin is a strong inducer of heme oxygenase-1 (HO-1) expression in vitro and in
      vivo. Whereas moderate overexpression of HO-1 is protective against oxidative
      stress, uncontrolled levels of HO-1 can be detrimental. Therefore, we evaluated
      the effects of apigenin (APG), a flavonoid involved in a number of
      phosphorylation pathways and also known to inhibit inducible genes, such as iNOS
      and COX-2, on HO-1 expression. Incubation of mouse embryonic fibroblasts with APG
      (5--40 microM) decreased hemin-induced HO-1 protein and mRNA expression. APG also
      reduced the induction of HO-1 promoter activity, as assessed by bioluminescence
      imaging, in NIH3T3 cells transfected with the 15-kb HO-1 promoter fused with the
      reporter gene luciferase (HO-1-luc). Furthermore, through the use of specific
      inhibitors, APG's effect was found to be unrelated to its PKC, CK 2, PI 3 K, p38,
      or ERK inhibitory activities. Quercetin (10--40 microM), also a flavonoid, also
      inhibited hemin-induced HO-1 expression. Additionally, in vivo studies using HO-1
      luc transgenic mice showed that APG (50 mg/kg) decreased hemin-induced HO
      activity and HO-1 protein expression in the liver. These results suggest that
      hemin-induced HO-1 expression can be attenuated by flavonoids, such as APG.

PMID- 16109303
TI  - Tyrosine nitration by superoxide and nitric oxide fluxes in biological systems:
      modeling the impact of superoxide dismutase and nitric oxide diffusion.
AB  - Tyrosine nitration is a posttranslational modification observed in many
      pathologic states that can be associated with peroxynitrite (ONOO(-)) formation.
      However, in vitro, peroxynitrite-dependent tyrosine nitration is inhibited when
      its precursors, superoxide (O(2)*(-)) and nitric oxide ((*)NO), are formed at
      ratios (O(2)*(-)/(*)NO) different from one, severely questioning the use of 3
      nitrotyrosine as a biomarker of peroxynitrite-mediated oxidations. We herein
      hypothesize that in biological systems the presence of superoxide dismutase (SOD)
      and the facile transmembrane diffusion of (*)NO preclude accumulation of O(2)*(-)
      and (*)NO radicals under flux ratios different from one, preventing the secondary
      reactions that result in the inhibition of 3-nitrotyrosine formation. Using an
      array of reactions and kinetic constants, computer-assisted simulations were
      performed in order to assess the flux of 3-nitrotyrosine formation (J(NO(2(-))Y))
      during exposure to simultaneous fluxes of superoxide (J(O(2)*(-))) and nitric
      oxide (J((*)NO)), varying the radical flux ratios (J(O(2)*(-))/ J((*)NO)), in the
      presence of carbon dioxide. With a basic set of reactions, J(NO(2(-))Y) as a
      function of radical flux ratios rendered a bell-shape profile, in complete
      agreement with previous reports. However, when superoxide dismutation by SOD and
      (*)NO decay due to diffusion out of the compartment were incorporated in the
      model, a quite different profile of J(NO(2(-))Y) as a function of the radical
      flux ratio was obtained: despite the fact that nitration yields were much lower,
      the bell-shape profile was lost and the extent of tyrosine nitration was
      responsive to increases in either O(2)*(-) or (*)NO, in agreement with in vivo
      observations. Thus, the model presented herein serves to reconcile the in vitro
      and in vivo evidence on the role of peroxynitrite in promoting tyrosine
      nitration.

PMID- 16109302
TI  - Redox response of the endogenous calcineurin inhibitor Adapt 78.
AB  - Adapt 78 (DSCR 1/calcipressin/MCIP 1) is a potent natural inhibitor of
      calcineurin, an important intracellular phosphatase that mediates many cellular
      responses to calcium. We previously reported two major cytosolic isoforms (1 and
      4) of Adapt 78, and that isoform 4 is an oxidative and calcium stress-response
      protein. Using a higher cell culture density and new antibody, we again observed
      that both major isoforms localized to the cytosol, but a significant level of
      isoform 4 (but not isoform 1) was also detected in the nucleus where it was
      present in the non-soluble region and not associated with RNA. Exposure of cells
      to hydrogen peroxide led to the significant loss of isoform 4 from the nucleus
      with a moderate increase in cytosolic localization. The change in isoform 4
      phosphorylation state in response to oxidative stress, characterized by a loss of
      the lesser (hypo) phosphorylated Adapt 78, was not due to accelerated
      degradation, although general Adapt 78 degradation was proteosome mediated.
      Finally, stimulation of Jurkat and primary T-lymphocyte signaling led to isoform
      4 induction. This induction was BAPTA, diphenylene iodonium, and N-acetylcysteine
      inhibitable, and accompanied by induction of the classic immune response mediator
      and calcineurin-pathway-stimulated interleukin-2. These studies reveal new redox
      related activities for Adapt 78 isoform 4, which may contribute to its known
      calcineurin-regulating and cytoprotective activities, and further suggest that
      Adapt 78 plays a role in basic T-cell response.

PMID- 16109304
TI  - Differential sensitization of cancer cells to doxorubicin by DHA: a role for
      lipoperoxidation.
AB  - Polyunsaturated fatty acids have been reported to enhance the cytotoxic activity
      of several anticancer drugs. In the present study, we observed that doxorubicin
      chemosensitization of breast cancer cell lines by docosahexaenoic acid (DHA, a
      long-chain omega-3 polyunsaturated fatty acid) was cell-line selective, affecting
      MDA-MB-231 and MCF-7 dox (a doxorubicin-resistant cell line) but not the parental
      MCF-7 cell line. DHA supplementation led to an increase in membrane phospholipid
      DHA level, but did not induce changes in intracellular [(14)C]doxorubicin
      accumulation. In MDA-MB-231, doxorubicin efficacy enhancement by DHA was linked
      to an increase in malondialdehyde level, a final product of lipid peroxidation.
      DHA elicited by itself a 3.7-fold malondialdehyde level increase, additive to
      that induced by doxorubicin. Addition of doxorubicin to DHA further increased the
      glutathione level, indicative of the generation of an oxidative stress. In
      contrast to MDA-MB-231, doxorubicin did not increase the malondialdehyde level in
      MCF-7, although DHA induced lipid peroxidation. Therefore in MCF-7, lipid
      peroxidation induced by DHA itself was not sufficient to trigger an oxidative
      stress and to subsequently increase sensitivity to doxorubicin. These data
      indicate that the differential effect of DHA among cells on drug toxicity results
      from a differential oxidative response to doxorubicin. Chemosensitization through
      fatty acids appears as a new promising adjuvant therapeutic paradigm, since omega
      3 fatty acids are physiological molecules found in food and are nontoxic in vivo.

PMID- 16109305
TI  - Kinetic study of the quenching reaction of singlet oxygen by tea catechins in
      ethanol solution.
AB  - A kinetic study of the quenching reaction of singlet oxygen ((1)O(2)) with
      catechins (catechin (CA), epicatechin (EC), epigallocatechin (EGC), epicatechin
      gallate (ECG), epigallocatechin gallate (EGCG)) and related compounds (5
      methoxyresorcinol (MR), 4-methylcatechol (MC), and n-propyl gallate (PG)) was
      performed in ethanol at 35 degrees C. MR, MC, and PG are considered to be a model
      of resorcinol (A)-, catechol (B)-, and gallate (G)-rings in catechins,
      respectively. The overall rate constants, k(Q) (= k(q) + k(r), physical quenching
      + chemical reaction), for the reaction of catechins with (1)O(2) increased in the
      order of PG < MR < MC < CA < EC < EGC < ECG < EGCG. In a comparison of the rate
      constants, the relationship between quenching rates and chemical structures is
      discussed. The catechins which have lower peak oxidation potentials, E(P), show
      higher reactivities. It was observed that the chemical reaction (k(r)) is almost
      negligible in the quenching reaction of (1)O(2) by catechins. The k(Q) values of
      EGCG (1.47 x 10(8) M(-1) s(-1)) and ECG (7.81 x 10(7)) were found to be larger
      than those of lipids (1.3 x 10(5)-1.9 x 10(5) M(-1) s(-1)), amino acids (<3.7 x
      10(7)), and DNA (5.1 x 10(5)). Further, these values are similar to those (1.15 x
      10(8)-2.06 x 10(8) M(-1) s(-1)) of alpha- and gamma-tocopherol, ubiquinol-10, and
      gamma-tocopherol hydroquinone (plastoquinol model). The result suggests that
      catechins may contribute to the protection of oxidative damage in biological
      systems, by quenching (1)O(2).

PMID- 16109306
TI  - Optimization of selenium status by a single intraperitoneal injection of Se in Se
      deficient rat: possible application to burned patient treatment.
AB  - In order to investigate the efficiency of a single selenium (Se) administration
      in restoring selenium status, Se and antioxidant enzymes were studied in an
      animal model of Se depletion. In Se-depleted animals receiving or not a single
      parenteral administration of Se, plasma, red blood cell (RBC), and tissue Se
      levels were measured concurrently with glutathione peroxidase (GPx) and
      superoxide dismutase (SOD) activities. The oxidative stress was assessed by
      thiobarbituric acid-reactive species (TBARs), total thiol groups, glutathione,
      and tocopherol measurements. Our study showed that Se depletion with alterations
      in the antioxidant defense system (Se and GPx activity decreases) led to an
      increase of lipid peroxidation, a decrease of the plasma vitamin E level, and SOD
      activation. Sodium selenite injection resulted after 24 h in an optimal plasma Se
      level and a reactivation of GPx activity. In liver, brain, and kidney, Se levels
      in injected animals were higher than those in reference animals. However, this
      single administration of Se failed to decrease free radical damage induced by Se
      depletion. Therefore, in burned patients who exhibit an altered Se status despite
      a daily usually restricted Se supplementation, the early administration of a
      consistent Se amount to improve the GPx activity should be of great interest in
      preventing the impairment of the antioxidant status.

PMID- 16109307
TI  - Bile acid modulates transepithelial permeability via the generation of reactive
      oxygen species in the Caco-2 cell line.
AB  - The barrier functions in epithelial and endothelial cells seem to be very
      important for maintaining normal biological homeostasis. However, it is unclear
      whether or how bile acids affect the epithelial barrier. We examined the bile
      acid-induced disruption of the epithelial barrier. We measured the
      transepithelial electrical resistance (TEER) of Caco-2 cells as a marker of
      disruption of the epithelial barrier. Reactive oxygen species (ROS) generation
      was also measured. Cholic acid (CA) decreased the TEER and increased
      intracellular ROS generation. PLA2 (phospholipase A2), COX (cyclooxygenase), PKC
      (protein kinase), ERK 1/2 (extracellular signal-regulated kinase 1/2), PI 3 K
      (phosphatidylinositol 3-kinase), p38 MAPK (p38 mitogen-activated protein kinase),
      MLCK (myosin light-chain kinase), NADH dehydrogenase, and XO (xanthine oxidase)
      inhibitors or ROS scavengers prevented the CA-induced TEER decrease. PLA2, COX,
      PKC, NADH dehydrogenase, and XO inhibitors prevented the CA-induced ROS
      generation but not ERK 1/2, PI 3 K, p38 MAPK, and MLCK inhibitors. If the cells
      were treated with ROS generators such as superoxide dismutase, the TEER
      decreased. ERK 1/2, PI 3 K, p38 MAPK, and MLCK inhibitors prevent these ROS
      generators from inducing the TEER decrease. These results suggest that ROS play
      an important role. In addition, PLA2, COX, PKC, NADH dehydrogenase, and XO are
      located upstream of the ROS generation, but ERK 1/2, PI 3 K, p38 MAPK, and MLCK
      are downstream during the signaling of CA-induced TEER alterations.

PMID- 16109308
TI  - Differences in gene expression profiles in dermal fibroblasts from control and
      patients with age-related macular degeneration elicited by oxidative injury.
AB  - The pathogenesis of age-related macular degeneration (AMD) is still unknown but
      there is growing evidence that a combination of both oxidative injury and genetic
      factors may play a role. One particle hypothesis proposes that dysregulation of
      multiple genes in response to an oxidative injury could contribute to the
      development of AMD. While direct examination of ocular cells from AMD patients is
      difficult, AMD also appears to have a systemic component. Therefore, as is the
      case with other central nervous diseases, peripheral sites may also manifest any
      underlying genetic abnormalities. For the present study, biopsy-derived
      fibroblasts from 4 patients with the early form and 4 patients with the late form
      of AMD and 3 age-matched control patients were grown in culture and treated with
      a nonlethal dose of the oxidative stimulus menadione. Gene expression patterns
      were quantitatively and qualitatively examined using Human Genome U95A GeneChips
      (Affymetrix) and verified by real-time PCR analysis. In response to the oxidative
      injury 755 genes were found to be upregulated at least twofold in one of the
      patients groups. Cluster analysis of expression profiles detected six patterns of
      dysregulation initiated by oxidative injury specific for the disease groups (98
      genes total). Clusters of genes dysregulated by the sublethal oxidative injury in
      either early and/or late AMD groups were further categorized by
      overrepresentation of GO "biological process" categories using Expression
      Analysis Systematic Explorer (EASE) software. This approach demonstrated that
      four major functional gene groups including inflammatory/innate immune response,
      transcriptional regulation, cell cycle, and proliferation were significantly
      overrepresented (Fisher test ranging from 0.0393 to 0.00018) in both AMD patients
      groups in response to the oxidative injury. Despite the small number of patients
      in the study, specific biological and statistical differences in gene expression
      profiles between control and AMD patients were identified but only in the
      presence of an environmental stimulus.

PMID- 16109309
TI  - Peroxide resistance in human and mouse lens epithelial cell lines is related to
      long-term changes in cell biology and architecture.
AB  - It is well established that the response of the cell to environmental stress is a
      major basis for cell modification. Such modification is believed to adapt the
      cell to better survive its environment. Oxidative stress, a major and ubiquitous
      stressing factor, was selected for investigating the cellular response to stress.
      Most studies investigating such cellular response have employed examination of
      the cell either during or shortly after exposure to stress. We have employed a
      different approach arguing that the short-term response to stress obscures the
      biological changes that allow the cell to continue to thrive in its new
      environment. Reflecting this concept, murine and human cell lines capable of
      surviving regular exposure to toxic levels of H(2)O(2) or TBOOH have been
      developed. It was found that certain fundamental long-term changes in cell
      biology had occurred. The peroxide-resistant cells are diploid rather than
      aneuploid, show fundamental changes in the cytoskeletal cellular structure,
      suggesting less rigid more flexible cells, express a new lower molecular mass of
      p53, a key stress protein responder involved in adaptation, and finally have an
      immunochemical modification in alphaA-crystallin, a small heat-shock protein.
      Previously, it was found that there is a dramatic increase in catalase and
      gluthathione S-transferase activity and a remarkable limited change in expression
      in other antioxidative genes in these cells. The impact of these changes is
      discussed. It is apparent that evolutionary cell modifications can occur in
      response to relatively rapid changes in environment over periods ranging from
      days to months rather than the thousands of years considered in most evolutionary
      modifications.

PMID- 16109310
TI  - Evaluation of a new copper(II)-curcumin complex as superoxide dismutase mimic and
      its free radical reactions.
AB  - A mononuclear (1:1) copper complex of curcumin, a phytochemical from turmeric,
      was synthesized and examined for its superoxide dismutase (SOD) activity. The
      complex was characterized by elemental analysis, IR, NMR, UV-VIS, EPR, mass
      spectroscopic methods and TG-DTA, from which it was found that a copper atom is
      coordinated through the keto-enol group of curcumin along with one acetate group
      and one water molecule. Cyclic voltammetric studies of the complex showed a
      reversible Cu(2+)/Cu(+) couple with a potential of 0.402 V vs NHE. The Cu(II)
      curcumin complex is soluble in lipids and DMSO, and insoluble in water. It
      scavenges superoxide radicals with a rate constant of 1.97 x 10(5) M(-1) s(-1) in
      DMSO determined by stopped-flow spectrometer. Subsequent to the reaction with
      superoxide radicals, the complex was found to be regenerated completely,
      indicating catalytic activity in neutralizing superoxide radicals. Complete
      regeneration of the complex was observed, even when the stoichiometry of
      superoxide radicals was 10 times more than that of the complex. This was further
      confirmed by EPR monitoring of superoxide radicals. The SOD mimicking activity of
      the complex was determined by xanthine/xanthine oxidase assay, from which it has
      been found that 5 microg of the complex is equivalent to 1 unit of SOD. The
      complex inhibits radiation-induced lipid peroxidation and shows radical
      scavenging ability. It reacts with DPPH radicals with rate constant 10 times less
      than that of curcumin. Pulse radiolysis-induced one-electron oxidation of the
      complex by azide radicals in TX-100 micellar solutions produced strongly
      absorbing ( approximately 500 nm) phenoxyl radicals, indicating that the phenolic
      moiety of curcumin remained intact on complexation with copper. The results
      confirm that the new Cu(II)-curcumin complex possesses SOD activity, free radical
      neutralizing ability, and antioxidant potential. Quantum chemical calculations
      with density functional theory have been performed to support the experimental
      observations.

PMID- 16109311
TI  - Redox regulation of cytokine-mediated inhibition of myelin gene expression in
      human primary oligodendrocytes.
AB  - Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the
      central nervous system (CNS) of unknown etiology. Several studies have shown that
      demyelination in MS is caused by proinflammatory mediators which are released by
      perivascular infiltrates and/or activated glial cells. To understand if
      proinflammatory mediators such as IL (interleukin)-1beta and TNF (tumor necrosis
      factor)-alpha are capable of modulating the expression of myelin-specific genes,
      we investigated the effect of these cytokines on the expression of myelin basic
      protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), myelin
      oligodendrocyte glycoprotein (MOG), and proteolipid protein (PLP) in human
      primary oligodendrocytes. Interestingly, both IL-1beta and TNF-alpha markedly
      inhibited the expression of MOG, CNPase, and PLP but not MBP, the effect that was
      blocked by antioxidants such as N-acetylcysteine (NAC) and pyrrolidine
      dithiocarbamate (PDTC). Consistently, oxidants and prooxidants like H(2)O(2) and
      diamide also markedly inhibited the expression of MOG, CNPase, and PLP.
      Furthermore, both IL-1beta and TNF-alpha induced the production of H(2)O(2).
      Taken together, these studies suggest that proinflammatory cytokines inhibit the
      expression of myelin genes in human primary oligodendrocytes through the
      alteration of cellular redox.

PMID- 16109312
TI  - Endogenous DNA damage clusters in human skin, 3-D model, and cultured skin cells.
AB  - Clustered damages-two or more oxidized bases, abasic sites, or strand breaks on
      opposing DNA strands within a few helical turns-are formed in DNA by ionizing
      radiation. Clusters are difficult for cells to repair and thus pose significant
      challenges to genomic integrity. Although endogenous clusters were found in some
      permanent human cell lines, it was not known if clusters accumulated in human
      tissues or primary cells. Using high-sensitivity gel electrophoresis, electronic
      imaging, and number average length analysis, we determined endogenous cluster
      levels in DNA from human skin, a 3-D skin model, and primary cultured skin cells.
      DNA from dermis and epidermis of human skin contained extremely low levels of
      endogenous clusters (a few per gigabase). However, cultured skin fibroblasts and
      keratinocytes-whether in monolayer cultures or in 3-D model skin cultures
      accumulated oxidized pyrimidine, oxidized purine, and abasic clusters. The levels
      of endogenous clusters were decreased by growing cells in the presence of
      selenium or by increasing cellular levels of Fpg protein, presumably by
      increasing processing of clustered damages. These results imply that the levels
      of endogenous clusters can be affected by the cells' external environment and
      their ability to deal with DNA damage.

PMID- 16109313
TI  - Interleukin-15 in hypertension: further insights into inflammation and vascular
      disease.

PMID- 16109314
TI  - Serum interleukin-15 concentration in patients with essential hypertension.
AB  - BACKGROUND: Interleukin (IL)-15 is one of the cytokines produced by neutrophils
      and monocytes/macrophages, and its expression is found immunohistochemically in
      inflammatory cells adjacent to vulnerable atherosclerotic plaques. However, the
      influence of systemic IL-15 on cardiovascular disease is still unclear.
      Therefore, we designed clinical investigations to clarify the relationship
      between cardiovascular complications and serum IL-15 levels. METHODS AND RESULTS:
      Three hundred ninety-nine patients with essential hypertension were analyzed. We
      divided the study subjects into the following three groups according to the
      modified World Health Organization-International Society of Hypertension
      classification of 1999: patients with no organ damage (n = 213), patients with
      mild organ damage (n = 128), and patients with severe organ damage (n = 58). We
      measured serum IL-15, highly sensitive C reactive protein, IL-6, soluble
      intercellular adhesion molecule, and soluble vascular cell adhesion molecule
      levels. Serum IL-15 concentration in patients with severe organ damage was
      significantly higher than that in those with no organ damage (P < .01) and those
      with mild organ damage (P < .01). Serum IL-15 concentration in patients with
      coronary artery disease or peripheral artery disease was significantly higher
      than that in those without coronary artery disease or peripheral artery disease.
      Moreover, serum IL-15 concentration in patients with lacunar infarction was
      significantly higher than that in those without lacunar infarction (P < .005). By
      multiple linear logistic regression analysis, serum IL-15 concentration was
      independently correlated with cardiovascular disease. CONCLUSIONS: These data
      suggest that a systemic inflammatory response involving IL-15 might be involved
      in the occurrence of cardiovascular disease in patients with essential
      hypertension.

PMID- 16109315
TI  - Prevalence, treatment, and control of chest pain syndromes and associated risk
      factors in hypertensive patients.
AB  - BACKGROUND: Prevalence of chest pain syndromes (CPS)-chest pain, angina pectoris,
      chronic angina, and preinfarction angina/intermediate coronary syndrome (ICS)
      among hypertensive patients and medical management of these disorders in primary
      care are not well defined. METHODS: The Hypertension Initiative primary care
      database with 72,508 hypertensives was analyzed to characterize prevalence and
      management of CPS. Patients with more than one CPS were categorized by the most
      severe diagnosis. RESULTS: Eleven percent of hypertensives had a CPS. Of these
      patients, 66% (5284) were diagnosed with chest pain only, 15% (1204) with angina,
      and 19% (1508) with ICS. More men than women were diagnosed with angina (18% v
      4%) and ICS (21% v 10%). More women than men were diagnosed with chest pain only
      (86% v 61%). African Americans received more chest pain diagnoses (71% v 62%),
      similar angina diagnoses (14% v 16%), and slightly fewer ICS diagnoses (15% v
      22%) than whites. Most striking, women and African Americans with CPS received
      fewer medications than men and whites, both overall and within diagnostic
      categories. Prescription rates differed more by gender (male/female) than by
      ethnic group (white/African American) for angiotensin-converting enzyme
      inhibitor, diuretics, aspirin, statins, and nitrates. Hypertensives with CPS
      received more medications and achieved better risk factor control than non-CPS
      hypertensives, but the majority remained above goal levels. CONCLUSIONS: Primary
      care physicians treat cardiovascular risk factors relatively aggressively in
      hypertensives with CPS. However, substantial numbers of these patients do not
      reach goal levels. Demographic differences in treatment represent opportunities
      to reduce disparities.

PMID- 16109316
TI  - Antihypertensive treatment alters the predictive strength of pulse pressure and
      other blood pressure measures.
AB  - BACKGROUND: The objective of this study was to assess whether antihypertensive
      treatment affects the predictive power of brachial pulse pressure. METHODS: Data
      from the First National Health and Nutrition Examination Survey Epidemiologic
      Follow Up Study were used to conduct Cox regression analyses. There were 487
      cardiovascular disease (CVD) and 348 coronary heart disease (CHD) deaths during
      an 8.6-year follow-up among 2939 hypertensive subjects 33 to 87 years of age. A
      correction was made for the regression-dilution bias. RESULTS: Pulse pressure
      (PP) was a significant single predictor for treated, but not untreated,
      hypertensive subjects. The hazard ratio (95% confidence interval) for CVD
      mortality for an 10-mm Hg increment of PP was 1.16 (95% CI = 1.08 to 1.25) for
      treated hypertensive subjects, and 1.12 (95% CI = 0.99 to 1.26) for untreated
      hypertensive subjects. Also, PP was a significant predictor after accounting for
      the effects of mean arterial pressure (MAP), but only in treated hypertensive
      subjects. The pattern was opposite for diastolic pressure (DBP). Analysis of
      antihypertensive treatment trends suggests that clinicians focused treatment more
      on hypertensive subjects with elevated DBP and low PP during the 1970s and early
      1980s, thereby causing DBP to become a weak predictor and PP a strong predictor
      among treated hypertensive subjects. This tendency was particularly noticeable at
      higher ages. For instance, among hypertensive subjects > or =65 years of age
      during this period, the percentage who were treated increased from 7.6% to 45.0%,
      and the ratio of subjects with isolated systolic hypertension to those with
      isolated diastolic hypertension among those who were untreated increased from
      11.2 to 45.1. CONCLUSIONS: The findings of this prospective study suggest that
      antihypertensive treatment can alter the predictive strength of PP and other
      blood pressure measures.

PMID- 16109317
TI  - White coat hypertension in centenarians.
AB  - BACKGROUND: To study white coat (WC) hypertension in centenarians, a cross
      sectional surveillance was carried out on Uygurs, a long-lived population in
      China. METHODS: Twenty-four-hour ambulatory blood pressure (BP) monitoring (ABPM)
      was performed in 33 centenarians (age range, 100 to 113 years) and compared with
      100 elderly subjects (age range, 65 to 70 years). All subjects were clinically
      healthy and capable of self-care. Subjects had no history, signs, or symptoms of
      cardiovascular disease and were receiving no medical treatments. Office BP, 24-h
      mean, daytime and night-time BP, pulse pressure, heart rate, standard deviation
      (SD), and coefficient of variation (CV) of the same variables were extracted from
      ABPM. The WC effect was defined as the difference between mean office and daytime
      BP. RESULTS: Centenarians demonstrated higher prevalence of WC hypertension,
      compared to elderly group (15% vs. 5%). The WC effect was also greater in
      centenarians than in elderly subjects, and was more marked for systolic BP than
      for diastolic BP and heart rate. The WC effect for systolic BP was positively
      correlated with both SD (r = 0.45, P < .01) and CV (r = 0.55, P < .01) for 24-h
      systolic BP in centenarians, but not in elderly subjects. CONCLUSIONS: Prevalence
      of WC hypertension was greater in centenarians than in elderly subjects. The WC
      effect and BP variation may be increased in centenarians. Previously observed
      higher BPs seen in very elderly individuals might be explained by the greater
      impact of WC hypertension.

PMID- 16109318
TI  - Impact of job and marital strain on ambulatory blood pressure results from the
      double exposure study.
AB  - BACKGROUND: Psychosocial stressors such as job strain and marital stress have
      been associated with a sustained increase in blood pressure (BP). METHODS: We
      evaluated whether job strain and marital cohesion were associated with ambulatory
      BP in workers with normal or untreated elevated BP using baseline data from the
      Double Exposure study. The study population included 248 male and female
      volunteers who were nonmedicated, employed, and living with a significant other,
      all for a minimum of 6 months. Blood pressure was measured with an ambulatory BP
      monitor and participants completed a diary that recorded time during work,
      spousal contact, and sleep. Job strain and marital cohesion were calculated from
      the Job Content Questionnaire and the Dyadic Adjustment Scale, respectively.
      RESULTS: Of the subjects, 54.4% were female with a mean age of 50.8 years (6.6,
      SD). In all, 21.3% reported job strain. Significant assocations were found
      between 24-h systolic BP (SBP) and alcohol consumption (P = .033), job strain (P
      = .007), male gender (P = .004), and age (P = .039) and was inversely associated
      with exercise (P = .037). An interaction between 24-h SBP, job strain, and
      marital cohesion was found such that greater marital cohesion was associated with
      lower SBP in subjects with job strain. CONCLUSIONS: Psychosocial factors may
      influence the development of early hypertension. This should be clarified by the
      cohort phase of the Double Exposure study.

PMID- 16109319
TI  - Effect of baseline cognitive function and antihypertensive treatment on cognitive
      and cardiovascular outcomes: Study on COgnition and Prognosis in the Elderly
      (SCOPE).
AB  - BACKGROUND: We examined whether cognitive function at baseline affected cognitive
      and cardiovascular outcomes in the Study on COgnition and Prognosis in the
      Elderly (SCOPE), a blood pressure (BP)-lowering intervention trial. METHODS:
      SCOPE included 4937 patients, aged 70 to 89 years, with mild-to-moderate
      hypertension and Mini Mental State Examination (MMSE) score > or =24. Double
      blind treatment was initiated with candesartan or placebo. Open-label therapy was
      added as needed to control BP, both in the candesartan (49%) and control (66%)
      groups. Mean follow-up was 3.7 years. Low cognitive function (LCF) at baseline
      was defined as MMSE score 24 to 28 (N = 2070), and high cognitive function (HCF)
      as MMSE score 29 to 30 (N = 2867). RESULTS: Mean BP reductions were approximately
      20/10 mm Hg both in LCF and HCF patients, with greater reductions in the
      candesartan group than in the control group. The incidence of dementia was higher
      in LCF than in HCF patients. A higher cardiovascular event rate observed in LCF
      patients was explained by older age and other cardiovascular risk factors at
      baseline. In LCF patients, the MMSE score declined less in the candesartan than
      in the control group (mean difference 0.49, 95% confidence interval 0.02 to 0.97,
      P = .04). Nonfatal stroke was reduced in the candesartan group in the total
      sample (28%, P = .04), with no difference between LCF (27%) and HCF (29%)
      patients. CONCLUSIONS: Elderly patients with mild-to-moderate hypertension and
      slightly impaired cognitive function (MMSE 24 to 28) are at increased risk of
      dementia and cardiovascular events. This analysis indicates that effective
      antihypertensive therapy may reduce cognitive decline and stroke incidence in
      these patients.

PMID- 16109320
TI  - A selective estrogen receptor modulator, tamoxifen, and membrane fluidity of
      erythrocytes in normotensive and hypertensive postmenopausal women: an electron
      paramagnetic resonance investigation.
AB  - BACKGROUND: Recent studies have shown that tamoxifen, which belongs to a group
      called selective estrogen receptor modulators (SERM), may exert protective
      effects against cardiovascular diseases and stroke in postmenopausal women. On
      the other hand, abnormalities in physical properties of the cell membranes may
      underlie the defects that are strongly linked to hypertension, stroke, and other
      cardiovascular diseases. The present study was performed to investigate the
      effects of tamoxifen on cell membrane fluidity (a reciprocal value of membrane
      microviscosity) in normotensive and hypertensive postmenopausal women. METHODS
      AND RESULTS: We used an electron paramagnetic resonance (EPR) and spin-labeling
      method. Tamoxifen significantly decreased the order parameter (S) for 5-nitroxide
      stearate (5-NS) and the peak height ratio (h(o)/h(-1)) for 16-NS obtained from
      EPR spectra of erythrocyte membranes in normotensive postmenopausal women (mean
      +/- SEM, order parameter value; control 0.719 +/- 0.002, n = 41; tamoxifen 1 x
      10(-7) mol/L 0.704 +/- 0.002, n = 41, P < .0001; tamoxifen 1 x 10(-6) mol/L 0.696
      +/- 0.002, n = 41, P < .0001; tamoxifen 1 x 10(-5) mol/L 0.692 +/- 0.002, n = 41,
      P < .0001). The finding indicated that tamoxifen increased the membrane fluidity
      and improved the membrane microviscosity of erythrocytes. The membrane action of
      tamoxifen was antagonized by the estrogen receptor antagonist ICI 182,780. The
      effect of tamoxifen was significantly potentiated by the nitric oxide (NO)
      donors, l-arginine and S-nitroso-N-acetylpenicillamine, and a cGMP analog 8-bromo
      cGMP. In contrast, the change evoked by tamoxifen was counteracted by the NO
      synthase inhibitors N(G)-nitro-l-arginine-methyl-ester and asymmetric dimethyl-l
      arginine. In hypertensive postmenopausal women, the membrane fluidity of
      erythrocytes was significantly lower than in normotensive postmenopausal women.
      The effect of tamoxifen on the membrane fluidity was more pronounced in
      hypertensive postmenopausal women than in normotensive postmenopausal women.
      CONCLUSIONS: These results showed that tamoxifen increased the membrane fluidity
      of erythrocytes and improved the rigidity of cell membranes in postmenopausal
      women, to some extent, through the NO- and cGMP-dependent mechanisms.
      Furthermore, the greater effect of tamoxifen in hypertensive postmenopausal women
      suggests that tamoxifen could have a beneficial effect in regulating the blood
      rheologic behavior and in the improvement of the microcirculation in
      hypertension.

PMID- 16109321
TI  - Demographic, environmental, and genetic predictors of metabolic side effects of
      hydrochlorothiazide treatment in hypertensive subjects.
AB  - BACKGROUND: Thiazide diuretics are recommended for first-line treatment of
      hypertension. Although considered safe and effective, their use is associated
      with dyslipidemia, hyperglycemia, and an increased risk of developing type 2
      diabetes. The aim of this study was to characterize interindividual variation in
      glucose and lipid responses to hydrochlorothiazide and to identify demographic,
      environmental, and genetic predictors associated with this variation. METHODS: A
      community-based sample of 585 adults with essential hypertension (291 African
      Americans [150 women and 141 men] and 294 non-Hispanic whites [126 women and 168
      men]) underwent monotherapy with hydrochlorothiazide for 4 weeks. Linear
      regression was used to construct prediction models for the changes in plasma
      total cholesterol, triglyceride, and glucose concentrations. RESULTS: The mean
      changes (+/- standard deviation) in response to hydrochlorothiazide were 6.13 +/-
      22.8 mg/dL for total cholesterol, 17.21 +/- 70 mg/dL for triglycerides, and 3.5
      +/- 9.5 mg/dL for plasma glucose. Ethnicity and baseline levels of the analytes
      were the only predictors that were significant for more than one response.
      Therefore, the mechanism for these metabolic effects are not entirely shared.
      CONCLUSIONS: Taken together, demographic, environmental, and genetic factors
      accounted for only 13% of the total variation in total cholesterol response, 17%
      of the variation in triglyceride response, and 11% of the variation in glucose
      response to hydrochlorothiazide, and less than half of this predicted variation
      in response was explained by measured genotypes.

PMID- 16109322
TI  - A novel quantitative trait locus on chromosome 1 with pleiotropic effects on HDL
      cholesterol and LDL particle size in hypertensive sibships.
AB  - BACKGROUND: High-density lipoprotein (HDL)-cholesterol, triglycerides, and LDL
      particle size are correlated lipid traits. Abnormal levels of these traits are
      frequent in hypertensive individuals and contribute to increased risk of coronary
      heart disease (CHD). We performed univariate and bivariate linkage analyses to
      identify genomic regions that influence levels of these traits and exert
      pleiotropic effects on the traits in hypertensive sibships. METHODS: Subjects
      included 691 non-Hispanic white individuals (mean age 63.1+/-8.5 years, 57%
      women, 78% hypertensive) ascertained through sibships with two or more
      individuals diagnosed with hypertension before age 60 years. The LDL particle
      size was measured by polyacrylamide gel electrophoresis and triglycerides were
      log-transformed to reduce skewness. Genotypes were measured at 366 microsatellite
      marker loci distributed across the 22 autosomes. Univariate and bivariate linkage
      analyses were performed using a variance components approach. RESULTS:
      Significant (P < .001) genetic correlations were confirmed for all pairwise
      combinations of the traits. Univariate linkage analyses demonstrated evidence of
      linkage (defined as multipoint LOD scores > or =1.3) for HDL-cholesterol on
      chromosomes 1p, 3p, 9q, and 18q; for log triglycerides on chromosome 10q; and for
      LDL particle size on chromosomes 2p and 8p. Pairwise bivariate linkage analyses
      of the three traits revealed a region with pleiotropic effects on HDL-cholesterol
      and LDL particle size on chromosome 1p (LOD score 4.48). CONCLUSIONS: These
      findings indicate the presence of a quantitative trait locus on chromosome 1 that
      has pleiotropic effects on HDL-cholesterol and LDL particle size and may
      therefore influence CHD susceptibility in hypertensive sibships.

PMID- 16109323
TI  - Analysis of the 11beta-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) in
      human essential hypertension.
AB  - BACKGROUND: The HSD11B2 gene, encoding the kidney isoenzyme 11beta-hydroxysteroid
      dehydrogenase, is a candidate for essential hypertension. We previously showed
      that the frequency of shorter alleles of a CA repeat polymorphism in the first
      intron of 11beta-HSD2 gene was significantly higher among salt-sensitive than
      salt-resistant individuals with hypertension. The aim of the study was to analyze
      the HSD11B2 gene to assess whether some of its variants might be involved in
      hypertension. METHODS: Exons 2, 3, 4, and 5 were screened by polymerase chain
      reaction-single-strand conformation polymorphism analysis in 292 hypertensive
      patients and 163 control subjects. The samples with variant electrophoretic
      patterns at single-strand conformation polymorphism were re-analyzed using an
      automated DNA sequencer. A case-control study was then performed by comparing
      genotype frequencies in hypertensive and normotensive subjects. RESULTS: Analysis
      of the HSD11B2 showed that in hypertensive patients there is a higher prevalence
      of two associated polymorphisms, Thr156/Thr(C468A) in exon 2 (ex2) and
      Glu178/Glu(G534A) in exon 3 (ex3), than in normotensive subjects (9% v 2.4%).
      This association did not correlate with salt sensitivity. C468A alone correlates
      significantly with hypertension (9%) and was identified only in 3% of control
      subjects (P < .05), whereas G534A was identified also in about 7% of normotensive
      subjects. The urinary free cortisol/urinary free cortisone ratio (UFF/UFE) was
      significantly higher in hypertensive patients compared with control subjects (P <
      .01). CONCLUSIONS: Two different polymorphisms of the HSD11B2 gene were observed.
      The association of both polymorphisms was significantly higher in hypertensive
      subjects than in control subjects. Its role should be further investigated, but
      it could be related to other mutations in the promoter region of HSD11B2 or to
      the modulation of 11beta-HSD2 mRNA processing in hypertensive subjects.

PMID- 16109324
TI  - Toward an improved diagnosis of the metabolic syndrome other clues to the
      presence of insulin resistance.
AB  - A substantial portion of the population of the United States has the Metabolic
      Syndrome, a condition that greatly increases risk for cardiovascular disease and
      diabetes. Insulin resistance, and the resulting compensatory hyperinsulinemia, is
      the principal pathophysiologic abnormality underlying the majority of these
      cases. Based on the most recent recommendations of the National Cholesterol
      Education Panel, such patients can be identified by the presence of three or more
      of the following traits: impaired fasting glucose, abdominal obesity,
      hypertension, elevated levels of triglycerides, and low concentrations of HDL
      cholesterol. However, a significant number of insulin resistant (and thus high
      risk) individuals will not be identified using these criteria. This discrepancy
      occurs because insulin resistance is a continuous variable, without an absolute
      cut-off between normal and abnormal, and those fitting the definition are the
      most insulin resistant. Moreover, easily applicable testing to diagnose insulin
      resistance accurately in the general population is currently not feasible. It is
      therefore necessary to broaden the criteria that define the metabolic syndrome to
      include other conditions associated with the presence of insulin resistance. Such
      conditions include the following: a family history of type 2 diabetes or coronary
      artery disease in first- or second-degree relatives, signs of an over active
      sympathetic nervous system, and elevated concentrations of uric acid. By
      recognizing these "other conditions," appropriate lifestyle changes and
      medication can be recommended to help prevent cardiovascular disease and diabetes
      from developing in these high-risk patients.

PMID- 16109325
TI  - Adrenal angiotensin: origin and site of generation.
AB  - BACKGROUND: Circulating angiotensin (Ang) II accumulates in adrenal tissue via
      binding to Ang II type 1 (AT1) receptors, reaching levels that are 15 to 20 times
      higher than in blood. Adrenal tissue contains a second renin transcript that
      gives rise to a truncated prorenin representing a cytosolic form of renin. Here
      we investigated what percentage of adrenal Ang II originates at adrenal tissue
      sites, and whether intracellular renin contributes to adrenal angiotensin
      production. METHODS: Concentrations of endogenous and iodine-125 (125I)-labeled
      Ang I and II were measured in adrenal tissue and blood from pigs after 125I-Ang I
      infusion. RESULTS: In the adrenal tissue in all animals, 125I-Ang I was
      undetectable. In untreated pigs, adrenal 125I-Ang II was 17 +/- 1 times arterial
      125I-Ang II, and tissue Ang I and II were 5 +/- 1 and 388 +/- 40 times higher
      than plasma Ang I and II. The AT1 receptor antagonist eprosartan reduced adrenal
      125I-Ang II accumulation by 80%, and increased plasma Ang II to a greater degree
      than tissue Ang II. As a consequence, eprosartan equally reduced the
      tissue/plasma concentration ratios of both Ang II and 125I-Ang II. Captopril did
      not alter 125I-Ang II accumulation, and acutely, but not chronically, reduced the
      adrenal Ang II/I ratio. CONCLUSIONS: More than 90% of adrenal Ang II originates
      at adrenal tissue sites. Local adrenal Ang II generation occurs extracellularly
      and is followed by internalization via AT1 receptor-mediated endocytosis.
      Enhanced angiotensin generation, combined with incomplete AT1 receptor blockade
      and the large adrenal AT1 receptor reserve, explains why eprosartan increased
      rather than decreased adrenal Ang II. Our data do not support angiotensin
      generation by truncated prorenin.

PMID- 16109326
TI  - Superoxide scavenging effects of N-acetylcysteine and vitamin C in subjects with
      essential hypertension.
AB  - BACKGROUND: It is not known whether the beneficial effects of N-acetylcysteine
      (NAC) in conditions associated with increased oxidative stress are caused by
      direct superoxide scavenging. We therefore compared the acute superoxide
      scavenging efficacy of NAC against vitamin C (VITC) on impaired endothelium
      dependent vasodilation in subjects with essential hypertension. METHODS: In a
      cross-over randomized study, the effects of intra-arterial administration of
      either NAC (48 mg/min) or VITC (18 mg/min) were examined in 15 subjects with
      essential hypertension and in 15 normotensive control subjects. Both endothelium
      dependent and endothelium-independent vasodilation were determined as forearm
      blood flow (FBF) response to the intra-arterial administration of acetylcholine
      (Ach) and sodium nitroprusside (NP) in doses of 12 and 48 mug/min and 3.2 and
      12.8 mug/min, respectively. RESULTS: Subjects with essential hypertension had
      impaired responses to both doses of Ach (Delta% FBF to higher dose of Ach: 325 +/
      146 in subjects with essential hypertension v 540 +/- 199 in control subjects; P
      = .02) and an impaired response to the higher dose of NP (330 +/- 108 v 500 +/-
      199; P = .03). The intra-arterial administration of NAC had no effect on these
      responses (higher dose of Ach: 325 +/- 146 without v 338 +/- 112 with NAC, NS).
      In contrast, intra-arterial VITC improved both the response to Ach (320 +/- 132
      without v 400 +/- 185 with VITC, P = .05) and to NP (383 +/- 162 v 447 +/- 170, P
      = .05). CONCLUSIONS: We found that NAC showed no statistically significant effect
      on either endothelium-dependent or endothelium-independent vasodilation in
      hypertensive subjects, whereas VITC did. We conclude that NAC is therefore not an
      effective superoxide scavenger in vivo. Other, nonimmediate effects such as the
      generation of glutathione may explain the beneficial effects of NAC in conditions
      associated with oxidative stress.

PMID- 16109327
TI  - Association of risk factors with increased pulse wave velocity detected by a
      novel method using dual-channel photoplethysmography.
AB  - BACKGROUND: Pulse wave velocity (PWV) is correlated with cardiovascular risk.
      This study presents a new method for measuring the arterial PWV by simultaneously
      recording the digital volume pulse through the finger and the toe by way of dual
      channel photoplethysmography (PPG). METHODS: In this study, 100 asymptomatic
      subjects (54 men and 46 women, 19 to 64 years of age) were enrolled. The PWV was
      measured both by dual-channel PPG (PWV-DVP) and by the standard method that
      current used applanation tonometry (PWV-AT). The developed dual-channel PPG
      system recorded digital volume pulse simultaneously from both the finger and toe.
      Time of pulse transition was measured on the time delay difference between two
      digital volume pulses. The PWV was calculated by dividing the distance between
      finger and toe by that of transit time. RESULTS: The PWV-DVP was significantly
      correlated with PWV-AT (r = 0.678, P < .01). With multivariate analysis
      controlled for age, heart rate, systolic blood pressure, and diastolic blood
      pressure, PWV-DVP was still significantly correlated with PWV-AT (r = 0.669, P <
      .01). Subjects with hypertension and dyslipidemia had significant higher PWV
      detected by both methods. CONCLUSION: This study showed that PWV measured with
      dual-channel PPG system correlated very well with that measured using the
      traditional method.

PMID- 16109328
TI  - C-reactive protein is related to arterial wave reflection and stiffness in
      asymptomatic subjects from the community.
AB  - BACKGROUND: Emerging data suggest that C-reactive protein (CRP), a marker of
      inflammation, is associated with functional properties of arteries. We
      investigated the relationship of CRP to measures of arterial wave reflection and
      stiffness (aortic augmentation index [AIX], carotid-femoral pulse wave velocity
      [PWV], and pulse pressure) in asymptomatic individuals from the community.
      METHODS: Subjects (n = 214) had a mean age of 59 years and 53% were men. CRP was
      measured by a high-sensitivity assay and values were log-transformed to reduce
      skewness. Radial artery waveforms were obtained by applanation tonometry, a
      validated transfer function was used to derive an ascending aortic pressure
      waveform, and AIX calculated. PWV was calculated from electrocardiogram-gated
      waveforms of the right carotid and right femoral artery obtained by applanation
      tonometry. RESULTS: Log CRP was correlated with AIX (r = 0.24, P = .0005), PWV (r
      = 0.25, P = .0002), and pulse pressure (r = 0.29, P < or = .0001). In separate
      backward elimination multiple regression analyses, log CRP was significantly
      associated with AIX (P = .038) and pulse pressure (P = .036), and marginally
      significantly associated with PWV (P = .054), after adjustment for heart rate,
      height, and coronary heart disease (CHD) risk factors (age, sex, body mass index,
      mean arterial pressure, total cholesterol, HDL cholesterol, diabetes,
      hypertension, and history of smoking). CONCLUSIONS: These results suggest that
      CRP, a marker of systemic inflammation, is related to measures of arterial wave
      reflection and stiffness in asymptomatic subjects from the community. Further
      studies are needed to understand the mechanisms underlying this association and
      the implications for assessment and management of CHD risk.

PMID- 16109329
TI  - Antioxidative protection in hypertensive patients treated with diuretics.
AB  - BACKGROUND: Recently results of the Antihypertensive and Lipid-Lowering Treatment
      to Prevent Heart Attack Trial (ALLHAT) showed that a thiazide diuretic was
      unsurpassed by any other drug class studied in achieving the level of
      cardiovascular protection, a finding reflected in the recent Seventh Report of
      the Joint National Committee on prevention, detection, evaluation, and treatment
      of high blood pressure (JNC7) recommendations. Oxidative stress has been found to
      be one of the key players in the pathophysiology of cardiovascular disease at
      large. The objective of this study was to check the hypothesis that diuretics may
      favorably affect the oxidative status of plasma, which could account in part for
      the results of recent trials. METHODS: In addition to the routine workup in a
      series of 39 medically treated hypertensive patients, we analyzed the level of
      antioxidative protection afforded by the ferric-reducing ability of plasma
      (FRAP), according to class of drug used. RESULTS: We found that patients taking
      diuretics had significantly better antioxidative protection expressed by the
      higher levels of FRAP. Although the limited number of patients did not allow us
      to exclude the influence of other variables in the multiple regression analysis,
      we did not observe any differences in the level of FRAP when the group was
      divided according to the other drug classes, gender (men versus women), smoking,
      diabetes mellitus, duration of treatment, concomitant therapy, or level of uric
      acid. CONCLUSIONS: The use of thiazide diuretics seems to be associated with
      better antioxidative protection. This observation may add to the explanation of
      the results of recent trials in hypertension.

PMID- 16109330
TI  - Hyperinsulinemia, insulin receptor number, and membrane microviscosity of
      erythrocytes in essential hypertension.

PMID- 16109331
TI  - Evaluation of the validity of three MABIS blood pressure monitors.

PMID- 16109332
TI  - In Reply to: ''Pulse pressure, plasma magnesium status, and antihypertensive
      therapy''.

PMID- 16109333
TI  - Pulse pressure, plasma magnesium status, and antihypertensive therapy.

PMID- 16109334
TI  - Impact of job and marital strain on ambulatory blood pressure.

PMID- 16109335
TI  - Protecting their adolescents from harm: parental views on STI vaccination.

PMID- 16109336
TI  - Predictors of STI vaccine acceptability among parents and their adolescent
      children.
AB  - PURPOSE: To identify attitudes and behavioral factors associated with parental
      intent to vaccinate their adolescent children against sexually transmitted
      infections (STI) and adolescent intent to accept vaccination for the prevention
      of STI. METHODS: In this cross-sectional study, 320 parents and their adolescent
      children (aged 12-17 years) were recruited from urban adolescent health clinics
      and private practice pediatric offices to complete audio, computer-assisted self
      interviews (A-CASI). Parents and their adolescents were asked about acceptability
      of gonorrhea, genital herpes, and human immumodeficiency virus/acquired immune
      deficiency syndrome (HIV/AIDS) vaccines. These three items were summed to create
      an STI vaccine acceptability scale, the primary outcome variable. Potential
      predictors measured included health beliefs, sociodemographic factors, and health
      and sexual behaviors. RESULTS: A substantial majority of parents and their
      adolescent children rated the three STI vaccines as very acceptable. Parental
      health beliefs and parental history of STI diagnosis were significant independent
      predictors of intent to vaccinate adolescent children against STI. Parental
      intent to vaccinate and having a friend who had engaged in sexual intercourse
      were significant independent predictors of adolescents' intent to accept STI
      vaccination. CONCLUSIONS: The majority of these parents and their adolescent
      children found STI vaccination very acceptable, suggesting that there will be
      great interest in these vaccines once they become available. Interventions
      designed to address parental health beliefs may prove successful at maintaining
      or increasing interest in STI vaccines. Adolescents are likely to look to their
      parents for guidance around acceptance of these vaccines, but personal
      experiences also may play a role.

PMID- 16109337
TI  - Parents'/guardians' willingness to vaccinate their children against genital
      herpes.
AB  - PURPOSE: To describe parents' acceptance of a hypothetical herpes simplex virus
      type 2 (HSV-2) vaccine, attitudes toward vaccine legislation, beliefs regarding
      appropriate timing of vaccination and correlates of vaccine acceptance. METHODS:
      A telephone survey of 315 parents/guardians in the Southeast United States.
      Descriptive statistics describe the sample's overall attitudes toward HSV-2
      vaccination, vaccine legislation, and age preferences. A logistic regression
      model tested the correlates of intention to vaccinate their children against HSV
      2. RESULTS: A majority of parents (69%) said they would have their children
      vaccinated. Nearly one-third (29.3%) thought genital herpes vaccination should
      take place between the ages of 11 and 13 years. Logistic regression revealed that
      females, single parents, parents whose children had influenza shots, those with
      more favorable attitudes to vaccination in general, and those who believed
      sexually transmitted disease (STD) vaccines would be beneficial were more likely
      to state they would vaccinate their children. CONCLUSIONS: Overall, a large
      proportion of parents indicated they would accept HSV-2 vaccination for their
      children. These results help identify those parents who may or may not be open to
      vaccinating their children against HSV-2 and inform future interventions to
      encourage HSV-2 vaccination. This research highlights the need for interventions
      that differentially target those who would and would not be likely to support
      vaccination of their children. Results also indicate that many parents believe
      vaccination should be given after an age when many adolescents have initiated
      sexual activity. Interventions to promote STD vaccines should not only encourage
      vaccination, but should also seek to change parental attitudes about optimal
      timing of the vaccination.

PMID- 16109338
TI  - High self-esteem among adolescents: longitudinal trends, sex differences, and
      protective factors.
AB  - PURPOSE: To better characterize self-esteem and to identify factors in early
      adolescence associated with high self-esteem in later adolescence. METHODS: The
      National Education Longitudinal Study provided a random, nationally
      representative sample of 8th grade adolescents who completed surveys in grades 8,
      10, and 12 (n = 16,489). We measured changes in self-esteem, and high versus low
      self-esteem. By using the Developmental Assets Model, predictor variables were
      selected to include intrinsic developmental assets (e.g., decision making) and
      extrinsic assets (e.g., safety). Logistic regression with separate modeling for
      sex identified assets that were predictive of high self-esteem, controlling for
      sociodemographic factors. RESULTS: Boys versus girls were more likely to report
      high self-esteem in all grades (all p < .001). For girls, factors predictive of
      high self-esteem in grade 12 were as follows: African-American (odds ratio [OR] =
      2.06) or Hispanic (OR = 1.52) race/ethnicity, positive family communication (OR =
      3.03), safety (OR = 1.50), and high self-esteem (OR = 3.03). For boys, factors
      were family income being above the federal poverty level (OR = 1.50), positive
      family communication (OR = 2.40), safety (OR = 1.41), religious community (OR =
      1.21), and high self-esteem (OR = 3.01) (all p < .05). CONCLUSIONS: Fewer
      adolescent girls than boys report high self-esteem. Adults may foster self-esteem
      in adolescents by providing positive communication through supportive and caring
      relationships.

PMID- 16109339
TI  - Family influences on the risk of daily smoking initiation.
AB  - PURPOSE: To examine developmental patterns and family influences on the risk of
      daily smoking initiation from adolescence to young adulthood. METHOD: A gender
      balanced, ethnically diverse urban sample of 808 children aged 10-11 years was
      surveyed in 1985 and followed prospectively to age 21 in 1996. Discrete-time
      survival analysis was used to assess the hazard of initiation of daily smoking
      during this time period, as well as the effects of family factors on the risk of
      daily smoking initiation. RESULTS: Less parental smoking, more strict family
      monitoring and rules, and stronger family bonding predicted a significantly lower
      risk of daily smoking initiation controlling for socio-demographic background.
      The decline in the impact of family bonding over time was marginally significant;
      however, none of the interactions between family factors and time were
      significant, indicating generally consistent family influences on daily smoking
      from age 10 to 21. CONCLUSIONS: The present findings indicate that parent smoking
      contributes to the onset of daily smoking in their teenagers even if parents
      practice good family management, hold norms against teen tobacco use, and do not
      involve their children in their own tobacco use. Smoking prevention programs
      should include components focused on parents of adolescents. To reduce risks for
      daily smoking among adolescents, it is important to encourage parents to stop or
      reduce their own smoking. In addition, these data indicate that parents can
      reduce their children's risk of daily smoking initiation by reducing family
      conflict, by maintaining strong bonds with their children, by setting clear
      rules, and by closely monitoring their children's behaviors.

PMID- 16109340
TI  - The timing of changes in girls' sexual cognitions and behaviors in early
      adolescence: a prospective, cohort study.
AB  - PURPOSE: This small, prospective cohort study of 162 12- to 15-year-old girls
      examines timing of changes in sexual cognitions and behaviors (breast fondling,
      genital contact, and sexual intercourse) over a 1-year period. METHODS: Girls
      from community sites in New York City provided information about sexual
      experiences and related cognitions (arousability, sexual agency, abstinence
      attitudes, perceived parental and peer approval, and sexual self-esteem) in 2
      interviews 1 year apart. RESULTS: Percentages who reported breast fondling,
      genital contact, and sexual intercourse (18%, 24%, and 6%) increased
      significantly over the year (42%, 44%, and 19%) and with age. For each behavior,
      analyses compared girls who did not report the behavior at either Time 1 or 2,
      those who reported by Time 2 but not 1, or those who reported at both time
      points. Girls with no breast fondling experience at either time point had
      stronger abstinence values, and lower arousability, agency, peer approval, and
      sexual self-esteem scores compared to girls who initiated breast fondling over
      the year (transitioners). Transitioners were markedly similar in sexual
      cognitions to girls with this experience before Time 1, suggesting that changes
      in sexual cognitions precede actual experience. A similar pattern was found
      between groups for genital contact. Few differences between groups by comparison
      were noted for sexual intercourse, which occurs later in the trajectory.
      CONCLUSIONS: Sexual experiences that occur before intercourse (e.g., breast
      fondling) are central to research on sexual development and related to greater
      changes in girls' sexual cognitions than is intercourse. Changes in cognitions
      precede, rather than follow, new sexual experiences.

PMID- 16109341
TI  - Prevalence of iron deficiency and anemia among strenuously trained adolescents.
AB  - PURPOSE: There is a lack of awareness among physicians, dieticians, and public
      health planners as to the prevalence of iron deficiency and anemia among
      adolescents undergoing strenuous physical training. The aim of this study was to
      estimate the prevalence of iron deficiency and anemia among male adolescents
      undergoing such activity. METHODS: We studied 292 male adolescents on the day of
      entry into a volunteer military unit. Hemoglobin (Hb), mean corpuscular volume,
      ferritin, iron, iron-transferrin saturation, and soluble transferrin receptor
      (TfR) were measured, and TfR-F index was calculated. RESULTS: The mean Hb level
      (+/-SD) in the study population was 14.7 +/- .9 g/dL (range, 10.8-16.8 g/dL),
      mean ferritin level was 50.6 +/- 32.6 ng/mL (range, 5.4-162.5 ng/mL), and mean
      iron level was 97.1 +/- 39.9 microg/dL (range, 24-267 microg/dL). The prevalence
      of anemia (Hb <14 g/dL) was 18.5%, and 3.4% had Hb concentrations less than 13
      g/dL. Iron deficiency (ferritin <22 ng/mL) was present in 18% of the subjects,
      and 11.3% had ferritin levels less than 17 ng/mL. The mean soluble transferrin
      receptor concentration was 1.9 +/- .8 mg/L, and the mean TfR-F index was 1.21 +/-
      .57. CONCLUSIONS: Nearly 19% of the study subjects had mild anemia at
      recruitment, and depletion of iron stores was observed among 18%. Overall, these
      changes were not accompanied by a significant increase in soluble TfR. This high
      prevalence is most likely the result of "sports anemia" due to the intense
      physical training regimen adopted prior to their recruitment.

PMID- 16109342
TI  - Knowledge about tobacco and subsequent use of cigarettes and smokeless tobacco
      among Swedish adolescents.
AB  - PURPOSE: To investigate whether knowledge of the risks and properties of tobacco
      among adolescents influences their future use of cigarettes and smokeless tobacco
      in different directions. METHODS: A prospective cohort study of 2581 adolescents
      whose knowledge of tobacco was assessed in the sixth grade by means of a multi
      item scale. Tobacco use was assessed by annual surveys up to the ninth grade.
      RESULTS: Knowledge level was not associated with future use. Items dealing with
      addictive properties of nicotine were prospectively associated with smokeless
      tobacco ("snus") use only. CONCLUSIONS: A high level of knowledge of the risks
      associated with tobacco is not a predictor of future nonuse or of a shift to
      smokeless tobacco rather than cigarettes. Attitudes and expectations may
      determine knowledge rather than vice versa.

PMID- 16109343
TI  - Comparisons of adolescent and parent willingness to participate in minimal and
      above-minimal risk pediatric asthma research protocols.
AB  - PURPOSE: Through the processes of permission and assent, parents and adolescents
      have a shared involvement in decision-making about adolescent research
      participation. Yet little empirical data exists examining the prevalence and
      contexts in which adolescents and parents disagree on research participation
      decisions. The purpose of this study was to compare parent and adolescent
      willingness to participate in minimal and above-minimal risk pediatric asthma
      research protocols. METHOD: Thirty-six adolescents diagnosed with asthma and a
      parent of each, independently rated their willingness to participate in nine
      pediatric asthma research protocol vignettes. The selected protocols were chosen
      by an expert panel as representative of typical minimal and above-minimal risk
      pediatric asthma studies. RESULTS: Parents and adolescents were significantly
      less likely to enroll in above-minimal risk studies. However, this was qualified
      by a finding that adolescents were significantly more willing than parents to
      enroll in above-minimal risk research. Across all nine studies, parents and
      adolescents held concordant views on participation decisions 60% of the time, on
      average. Perception of potential study benefit was the most frequent reason
      provided for participation decisions by both parents and adolescents. CONCLUSION:
      Parents and their adolescents report substantial discordance in their views about
      participating in asthma research across a variety of protocols. These differences
      of opinion highlight the need to carefully consider the process by which families
      are offered the option of adolescent research participation. Investigators may
      want to adopt recruitment procedures that involve adolescents in initial
      discussions, especially for above-minimal risk studies.

PMID- 16109344
TI  - Evaluating a teen STD prevention Web site.
AB  - PURPOSE: Teens are at higher risk than other age groups for acquiring sexually
      transmitted diseases (STDs) because of biological and behavioral risk factors,
      but they have few STD prevention resources. Little is known about how teens use
      the Internet to seek this information. A pilot study was conducted to measure
      audience and information-seeking characteristics of the www.iwannaknow.org Web
      site. METHODS: In addition to a formative content analysis and a usability study,
      an online survey was designed, pilot tested, revised, and launched for three
      months. This paper briefly describes the first two formative study components,
      and then focuses on the online survey. RESULTS: The content analyses and the
      usability tests were useful for revising the site content and aesthetics and
      preparing the online survey. Fewer than half of all participants (N=3,489) were
      between 13 and 17 (n=1,242), the intended site demographic. Most accessed the
      Internet from home. The most frequent topic of interest was sexual expression,
      followed by teen sexuality, virginity, relationships, contraception, and then STD
      information and these varied by age and gender. CONCLUSIONS: Methods and findings
      will assist researchers, Web site developers, and health educators to refine
      these evaluation methods, develop effective Web sites, and tailor STD prevention
      messages by age group and gender. The Internet is a cost-effective method for
      educating teens and those who care for or work with teens about STD risks and
      prevention, however, more research is needed to assess the behavioral effects of
      online interventions.

PMID- 16109345
TI  - The Internet: a window on adolescent health literacy.
AB  - PURPOSE: Adolescents are well served by the Internet through school access, but
      they will only derive maximum benefit from this information resource if they are
      able to search for, evaluate, and use its online information effectively.
      Internet use, however, requires significant literacy skills, and little is known
      about the health literacy of adolescents. The aim of this paper is to describe
      functional, critical, and interactive health literacy challenges experienced by
      adolescent students when using the Internet for online health information.
      METHODS: Twenty-six focus groups with 157 adolescent students, aged 11-19,
      conducted within a convenience sample of middle and high schools in diverse
      geographical and socioeconomic settings in the United Kingdom (UK) and United
      States of America (US) between May 2001 and May 2002. RESULTS: Many students
      cited difficulties in accessing health information online. Functional health
      literacy challenges included, for example, spelling medical terms correctly and
      being able to construct questions describing symptoms accurately. Critical
      challenges included discerning relevance of information retrieved by search
      engines and knowing which sites to trust. Interactive challenges included the
      appropriate application of health information to address personal health concerns
      within their local neighborhood. CONCLUSIONS: Exploring the challenges faced when
      adolescents search for online health information indicates deficiencies regarding
      health literacy skills. Difficulties regarding functional, critical, and
      interactive skills were all present. The Internet may offer opportunities for
      identifying such deficiencies and building better health literacy skills among
      adolescents, as part of health curriculum interventions to improve the
      population's future health.

PMID- 16109346
TI  - Adolescent pregnancy: do expectations affect intentions?
AB  - OBJECTIVE: To establish the relationship between expectations about the effects
      of childbearing on specific aspects of life and the strength of the desire to
      remain nonpregnant during adolescence. We hypothesized that the absence of
      negative childbearing expectations is associated with an increase in the odds
      that sexually active, inadequately contracepting teenage girls are cognitively
      susceptible to conception. METHOD: A racially and ethnically diverse group of 351
      nulligravida, inadequately contracepting teenagers was studied. Participants
      responded to 60 items that asked about their expectation about the effects of
      becoming pregnant and not doing so. Analyses were performed to determine the
      factorial structure of the childbearing expectations items and their relationship
      to cognitive susceptibility to conception, defined as the lack of desire to
      remain nonpregnant. RESULTS: The analysis yielded a 9-factor solution for the
      childbearing expectations items. All 9 sub-scales exhibited acceptable
      reliability coefficients, stable factor patterns, and correlated significantly
      with the desire to remain nonpregnant. A dose-dependent relationship suggestive
      of causality was also apparent. In stepwise regression the sub-scales that
      assessed the anticipated effect of childbearing on future plans, self-esteem, and
      boyfriend relations remained significant and accounted for 56% of the variance in
      the desire to remain nonpregnant. The lengthy research instrument was reduced to
      an 8-item screening tool without loss of psychometric integrity or explanatory
      power. CONCLUSIONS: Childbearing expectations reflect distinct concepts and
      account for a significant portion of the variance in the desire to remain
      nonpregnant during adolescence. Thus the 8-item screening tool we validated might
      be used to formulate a differential diagnosis for the enigmatic behavior of teens
      who say they do not "want" to become pregnant but do not "mind" doing so enough
      to try to avoid conceiving by default.

PMID- 16109347
TI  - HIV and sexual health knowledge and sexual experience among Australian-born and
      overseas-born students in Sydney.
AB  - PURPOSE: To examine differences between Australian-born and Asian-born first-year
      university students in Sydney in their sexual behavior and knowledge about the
      prevention and transmission of human immunodeficiency virus (HIV) and other
      sexually transmissible infections (STIs). METHODS: Students were recruited from a
      stall during the student Orientation Week in both 2002 and 2003 at the University
      of New South Wales. A short questionnaire was completed and returned anonymously.
      Data on age, gender, country of birth, sexual behavior, and sexual health
      knowledge were collected. A score was calculated based on the sum of the correct
      answers given to 12 HIV/STI transmission and prevention questions. The students
      were then divided into three groups according to their country of birth
      (Australia, Asia, and elsewhere) and their knowledge scores were compared.
      Students born in certain Asian countries were also asked their perception of the
      HIV epidemic in their home country compared with Australia. RESULTS: A total of
      1185 first-year students completed the questionnaire. Although older on average,
      Asian-born students were less likely to have had sexual intercourse and had had
      fewer sexual partners. They also had consistently poorer HIV/STI knowledge scores
      than Australian-born students. Students born in China, Hong Kong, Indonesia,
      Malaysia, and Singapore but not Thailand underestimated the prevalence of HIV in
      their country of birth in comparison with Australia. CONCLUSION: The combination
      of poorer knowledge, apparent misconception of the extent of HIV epidemic in
      their home country (or Australia), and potential later frequent travel indicates
      a potential risk for later transmission of HIV/STIs. The university is an
      underused setting for prevention health education.

PMID- 16109348
TI  - Asynchronous bilateral adnexal torsion in a 13-year-old adolescent: our
      experience of a rare case with review of the literature.
AB  - Adnexal torsion is a serious condition and delay in surgical intervention may
      result in loss of the tube and/or ovary. Children and adolescents who have
      suffered from uterine adnexal torsion may be at risk for asynchronous torsion of
      the contralateral uterine adnexa. We report the case of sequential bilateral
      torsion of uterine adnexa in a 13-year-old girl, resulting in right and
      subsequently left salpingo-oophorectomy because of gross evidence of total
      necrosis in both uterine adnexa. After the castration the patient was started on
      hormone replacement therapy. Families of children who suffered from ovarian
      torsion and unilateral ovarian loss should be educated about the risk of the
      contralateral ovary for future torsion and should be encouraged to seek immediate
      medical help with the recurrence of abdominal pain.

PMID- 16109349
TI  - Parental acceptance of the human papillomavirus vaccine.
AB  - We conducted focus groups and individual interviews to explore parental views on
      the human papillomavirus (HPV) vaccine. Parents were generally positive about the
      HPV vaccine. Some participants perceived their children were not at risk for
      acquiring HPV and questioned vaccinating young adolescents against HPV. Vaccine
      education should target parental beliefs about HPV and the optimal age for HPV
      vaccine administration.

PMID- 16109350
TI  - Substance use among rural adolescent virgins as a predictor of sexual initiation.
AB  - Longitudinal data from 746 virgins (310 males) aged 12 to 16 years were analyzed
      to assess the relationship between baseline substance use and sexual initiation
      3, 6, and 9 months later. Compared to virgins with no substance use, virgins who
      had used three or more substances were three times more likely to initiate sex
      over the ensuing 9 months. The use of alcohol, tobacco, and marijuana and the use
      of more than three substances are highly specific for predicting sexual
      initiation.

PMID- 16109351
TI  - Ipecac syrup abuse, morbidity, and mortality: isn't it time to repeal its over
      the-counter status?
AB  - PURPOSE: To review and address the abuse of ipecac, describing its epidemiology,
      toxicity, clinical characteristics, and laboratory assessment. METHODS: A Medline
      search (1980-2003) for Ipecac abuse and Ipecac toxicity, n = 34. RESULTS: Ipecac
      abuse occurs predominantly among adolescent and young adult females who are
      either experimenting with purging or have an eating disorder. Psychiatric
      comorbidity is common. Death can occur and is usually of cardiac origin.
      Morbidity includes myocarditis with arrhythmias, myositis, gastroesophageal
      pathology, including Mallory Weiss tears, diarrhea, and metabolic abnormalities
      (alkalosis, hypokalemia, dehydration). The injuries can reverse with cessation of
      ipecac use. A high index of suspicion is needed for early detection. Classic
      findings are abnormal EKG and echocardiography and/or elevation of muscle enzymes
      (CPK, adolase). Emetine, the alkaloid in ipecac, can be confirmed in serum,
      urine, and tissue by high performance liquid chromatography. CONCLUSIONS: Ipecac
      abuse is dangerous, even deadly. However, if abuse is discontinued, cardiac and
      muscle damage tends to reverse. Were ipecac syrup to remain an over- the-counter
      medication, or become a prescription medication, more stringent warning labels
      ought to be included and further education be provided about its toxicity and
      potential for abuse. Removing ipecac from the over-the-counter category would
      best eliminate its potential for abuse.

PMID- 16109353
TI  - Cell-mediated immunity and head and neck cancer: with special emphasis on betel
      quid chewing habit.
AB  - Betel quid (BQ) chewing is popular in Taiwan, India, and many southeast-Asian
      countries. BQ chewing has strong association with the risk of oral leukoplakia
      (OL), oral submucous fibrosis (OSF), and oral cancer (OC). BQ components exhibit
      genotoxicity and may alter the structure of DNA, proteins and lipids, resulting
      in production of antigenicity. BQ ingredients are also shown to induce
      keratinocyte inflammation by stimulating the production of prostaglandins, TNF
      alpha, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF)
      in keratinocytes. These events may provoke tissue inflammation, early cell
      mediated immunity (CMI), and immune surveillance in BQ chewers. However, BQ
      components also directly affect the functional activities of immunocompotent
      cells, and moreover tumor cells may hypo-respond to the CMI via diverse
      mechanisms such as induction of apoptosis of lymphocytes, induction of production
      of suppressor T cells, downregulation of MHC molecules in tumor cells, etc.
      Clinically, an alteration in lymphocyte subsets, a decrease in total number of
      lymphocytes, and a reduction in functional activities of CMI have been observed
      in isolated peripheral blood mononuclear cells (PBMC) and tumor infiltrated
      lymphocytes (TIL) in patients with OSF, OL or OC. Adaptation of tumor cells to
      immune system may promote clonal selection of resistant tumor cells, leading to
      immune tolerance. Future studies on effects of BQ components on CMI and humoral
      immunity in vitro and in vivo can be helpful for chemoprevention of BQ-related
      oral mucosal diseases. To elucidate how virus infection, tobacco, alcohol and BQ
      consumption, and other environmental exposure affect the immune status of
      patients with oral premalignant lesions or OC will help us to understand the
      immunopathogenesis of OC and to develop immunotherapeutic strategies for OC.

PMID- 16109354
TI  - Management of mandibular invasion: when is a marginal mandibulectomy appropriate?
AB  - There has been a great deal of controversy regarding the appropriate method of
      management of oral cavity and oropharyngeal tumors that invade the mandible. The
      inability to acquire intraoperative bone margins can make the decision process
      complex. Preoperative imaging offers several advantages, however, there is no
      single modality that has proven accurate. Intraoperative assessment has been
      suggested as a method of evaluation, however, this approach does not allow for
      preoperative planning. The following is a review of the current literature
      regarding mandibular invasion and the indications for a marginal mandibulectomy.

PMID- 16109355
TI  - A gap in the market.

PMID- 16109356
TI  - Lack of epidemiological data on secondary stroke prevention.

PMID- 16109357
TI  - Third gene identified for hereditary headache.

PMID- 16109358
TI  - Statin therapy in Alzheimer's disease.

PMID- 16109359
TI  - CSF testing for multiple sclerosis.

PMID- 16109360
TI  - Relation between migraine and stroke.
AB  - A complex bidirectional relation between migraine, mostly migraine with aura
      (MA), and ischaemic stroke is known. A cerebral infarction can occur during a MA,
      and MA is a risk factor for ischaemic stroke, particularly in young women.
      Conversely, cerebral ischaemia can induce MA. Both ischaemic stroke and MA might
      be consequences of many underlying vascular disorders. Despite the relation
      between migraine and stroke, migraine as a primary headache disorder is mostly
      benign.

PMID- 16109361
TI  - Neurological complications of HIV infection.
AB  - Cognitive disorders, vacuolar myelopathy, and sensory neuropathies associated
      with HIV are the most common disorders in patients with HIV AIDS, and are the
      focus of this review. These disorders are treatable and of those associated with
      HIV AIDS the pathogenic mechanisms are the most understood. Although triggered by
      productive HIV macrophage infections, aberrant immune activation plays a major
      role in inducing the CNS disorders. Novel therapies aimed at these inflammatory
      mechanisms can be effective. The sensory neuropathies associated with HIV
      infection are a major cause of morbidity; incidence may be increased by the toxic
      effects of specific antiretroviral drugs within the peripheral nervous system.

PMID- 16109362
TI  - Quality of life and its assessment in multiple sclerosis: integrating physical
      and psychological components of wellbeing.
AB  - Health-related quality of life (HRQoL) has been more intensively studied in
      multiple sclerosis (MS) than in any other neurological disorder. Traditional
      medical models of impairment and disability are an incomplete summary of disease
      burden. Quality of life can be thought of as the sum of all sources of
      satisfaction (including anticipated sources) minus all threats (including
      anticipated threats). Many psychosocial factors-including coping, mood, self
      efficacy, and perceived support-influence the quality of life of patients with MS
      more than biological variables such as weakness or extent of MRI lesions.
      Neuropsychiatric complications such as cognitive impairment and fatigue are also
      important predictors, even in those patients in the early stages of the disease.
      We review generic and specific HRQoL measures to help clinicians choose the most
      appropriate therapies. Subjective (self-report) HRQoL measures may serve to alert
      clinicians to areas that would otherwise be overlooked. Studies of new
      interventions should include an assessment of HRQoL not just impairment or
      disability alone.

PMID- 16109363
TI  - Glatiramer acetate in multiple sclerosis: update on potential mechanisms of
      action.
AB  - Glatiramer acetate is a synthetic random copolymer approved for the
      immunomodulatory therapy of relapsing-type multiple sclerosis (MS). Previous work
      has focused on the effects of this drug on T cells, especially the glatiramer
      acetate-induced shift of the cytokine profile towards those characteristic of T
      helper-2 (Th2) cells. Glatiramer acetate was thought to bring about this Th2
      shift by acting like an altered peptide ligand but more recent work has shown
      that the drug notably affects the properties of antigen-presenting cells, such as
      monocytes and dendritic cells. These new observations might offer an explanation
      for the previously observed Th2 shift. In this review, we focus on these new
      findings. We address several controversial issues, including the possible
      neurotrophic effects of glatiramer acetate, the potential role of neutralising
      antibodies to the drug, and attempts to develop biomarkers of the treatment
      response. Finally, we will think about how a better understanding of glatiramer
      acetate might help the development of new immunomodulatory agents for MS.

PMID- 16109364
TI  - Preclinical Alzheimer's disease: diagnosis and prediction of progression.
AB  - BACKGROUND: From the modest but important breakthroughs in the treatment of
      Alzheimer's disease (AD), diagnostic focus has increasingly shifted to the
      accurate detection of the earliest phase of the illness. The challenge of
      distinguishing preclinical AD from changes of normal ageing or established AD,
      has been recognised in several attempts at clinical classification. Of these
      attempts, Mayo Clinic's mild cognitive impairment (MCI) has received significant
      attention, although it has not been internationally accepted. Not all people
      diagnosed as having MCI will develop AD, hence there is a need to reliably
      predict progression. RECENT DEVELOPMENTS: Research in the identification of
      people with MCI who will develop AD via the use of neuropsychological tests,
      neuroimaging (both structural and functional), CSF analysis, and other
      biomarkers, either in isolation or in combination, has progressed rapidly. In
      this article we summarise findings from relevant recent longitudinal studies.
      WHERE NEXT?: There are increasing calls to recognise the pathological nature of
      MCI and to develop international diagnostic guidelines. Such uniform application
      of MCI criteria can then lead to clearer evidence of its diagnostic and
      therapeutic benefit. In developing these guidelines, the crucial presence of
      functional deficit arising from cognitive decline (which diagnoses dementia and
      excludes MCI) needs to be investigated in a standardised manner. Also needed are
      good-quality normal-values data on the various tests used to predict progression
      in preclinical AD.

PMID- 16109365
TI  - Are some strokes preventable? The potential role of transcranial doppler in
      transient ischaemic attacks of carotid origin.
AB  - Transient ischaemic attacks (TIA) are more than just ministrokes. The high
      frequency of early stroke following TIA has resulted in the recent publication of
      guidelines in the UK. The guidelines recommend that patients attend a
      neurovascular clinic within 7 days of the index event to expedite investigation
      and treatment and so reduce the risk of a subsequent (potentially more serious)
      neurological event. After a TIA or stroke caused by carotid-artery disease, there
      is an increase in cerebral microemboli detectable by transcranial doppler (TCD).
      High microembolic loads appear to be surrogate markers for future neurological
      events, and the pharmacological efficacy of therapeutic interventions can now be
      rapidly and non-invasively assessed in the clinic or at the bedside. Medical
      treatments can now be optimised, avoiding the need for urgent or emergency
      carotid surgery and therefore allowing patients to undergo safer elective surgery
      when appropriate.

PMID- 16109366
TI  - TPX or not TPX?
AB  - An Aurora A regulatory module has been identified in two different proteins: TPX2
      in Xenopus laevis and TPXL-1 in C. elegans. The diverse roles of these two
      proteins in spindle assembly leave us to beckon the true C. elegans TPX2 ortholog
      to center stage.

PMID- 16109367
TI  - Jun: stealth, stability, and transformation.
AB  - A recent paper by Wei and collaborators in Cancer Cell sheds light on the effects
      of one of the mutations in v-Jun and has broad implications for our understanding
      of control mechanisms that direct the timing of important cell cycle functions
      (Wei et al., 2005).

PMID- 16109368
TI  - New wrinkles and folds in site-specific recombination.
AB  - The new work of reveals a new site-specific recombination strategy to establish
      lysogeny, in which a double-stranded recombination substrate is assembled from
      the folded single-stranded DNA genome of the filamentous Vibrio cholerae phage
      CTXphi. This strategy allows the phage to use the host's recombinases while at
      the same time preventing inappropriate excision of the prophage.

PMID- 16109369
TI  - The developmental timing regulator AIN-1 interacts with miRISCs and may target
      the argonaute protein ALG-1 to cytoplasmic P bodies in C. elegans.
AB  - In metazoans, microRNAs (miRNAs) carry out various regulatory functions through
      association with multiprotein miRNA-induced silencing complexes (miRISCs) that
      contain Dicer and Argonaute proteins. How miRNAs regulate the expression of their
      mRNA targets remains a major research question. We have identified the C. elegans
      ain-1 gene through a genetic suppressor screen and shown that it functions with
      the heterochronic genetic pathway that regulates developmental timing.
      Biochemical analysis indicates that AIN-1 interacts with protein complexes
      containing an Argonaute protein, Dicer, and miRNAs. AIN-1 shares homology with
      the candidate human neurological disease protein GW182, shown to localize in
      cytoplasmic processing bodies that are sites of mRNA degradation and storage. A
      functional AIN-1::GFP also localizes at the likely worm processing bodies. When
      coexpressed from transgenes, AIN-1 targets ALG-1 to the foci. These results
      suggest a model where AIN-1 regulates a subset of miRISCs by localization to the
      processing bodies, facilitating degradation or translational inhibition of mRNA
      targets.

PMID- 16109370
TI  - Structural basis for the activation of microtubule assembly by the EB1 and
      p150Glued complex.
AB  - Plus-end tracking proteins, such as EB1 and the dynein/dynactin complex, regulate
      microtubule dynamics. These proteins are thought to stabilize microtubules by
      forming a plus-end complex at microtubule growing ends with ill-defined
      mechanisms. Here we report the crystal structure of two plus-end complex
      components, the carboxy-terminal dimerization domain of EB1 and the microtubule
      binding (CAP-Gly) domain of the dynactin subunit p150Glued. Each molecule of the
      EB1 dimer contains two helices forming a conserved four-helix bundle, while also
      providing p150Glued binding sites in its flexible tail region. Combining
      crystallography, NMR, and mutational analyses, our studies reveal the critical
      interacting elements of both EB1 and p150Glued, whose mutation alters microtubule
      polymerization activity. Moreover, removal of the key flexible tail from EB1
      activates microtubule assembly by EB1 alone, suggesting that the flexible tail
      negatively regulates EB1 activity. We, therefore, propose that EB1 possesses an
      auto-inhibited conformation, which is relieved by p150Glued as an allosteric
      activator.

PMID- 16109371
TI  - Structural basis for the cytoskeletal association of Bcr-Abl/c-Abl.
AB  - The Bcr-Abl tyrosine kinase causes different forms of leukemia in humans.
      Depending on its position within the cell, Bcr-Abl differentially affects
      cellular growth. However, no structural and molecular details for the anticipated
      localization determinants are available. We present the NMR structure of the F
      actin binding domain (FABD) of Bcr-Abl and its cellular counterpart c-Abl. The
      FABD forms a compact left-handed four-helix bundle in solution. We show that the
      nuclear export signal (NES) previously reported in this region is part of the
      hydrophobic core and nonfunctional in the intact protein. In contrast, we could
      identify the critical residues of helix alphaIII that are responsible for F-actin
      binding and cytoskeletal association. We propose that these interactions
      represent a major determinant for both Bcr-Abl and c-Abl localization.

PMID- 16109372
TI  - Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB
      on exon definition.
AB  - Fas exon 6 can be included or skipped to generate mRNAs encoding, respectively, a
      membrane bound form of the receptor that promotes apoptosis or a soluble isoform
      that prevents programmed cell death. We report that the apoptosis-inducing
      protein TIA-1 promotes U1 snRNP binding to the 5' splice site of intron 6, which
      in turn facilitates exon definition by enhancing U2AF binding to the 3' splice
      site of intron 5. The polypyrimidine tract binding protein (PTB) promotes exon
      skipping by binding to an exonic splicing silencer and inhibiting the association
      of U2AF and U2 snRNP with the upstream 3' splice site, without affecting
      recognition of the downstream 5' splice site by U1. Remarkably, U1 snRNP-mediated
      recognition of the 5' splice site is required both for efficient U2AF binding and
      for U2AF inhibition by PTB. We propose that TIA-1 and PTB regulate Fas splicing
      and possibly Fas-mediated apoptosis by targeting molecular events that lead to
      exon definition.

PMID- 16109374
TI  - Conformational change in the catalytic site of the ribonuclease YoeB toxin by
      YefM antitoxin.
AB  - The eubacterial chromosome encodes various addiction modules that control global
      levels of translation through RNA degradation. Crystal structures of the
      Escherichia coli YefM2 (antitoxin)-YoeB (toxin) complex and the free YoeB toxin
      have been determined. The structure of the heterotrimeric complex reveals an
      asymmetric disorder-to-order recognition strategy, in which one C terminus of the
      YefM homodimer exclusively interacts with an atypical microbial ribonuclease
      (RNase) fold of YoeB. Comparison with the YefM-free YoeB structure indicates a
      conformational rearrangement of the RNase catalytic site of YoeB, induced by
      interaction with YefM. Complementary biochemical experiments demonstrate that the
      YoeB toxin has an in vitro RNase activity that preferentially cleaves at the 3'
      end of purine ribonucleotides.

PMID- 16109373
TI  - Polypyrimidine tract binding protein blocks the 5' splice site-dependent assembly
      of U2AF and the prespliceosomal E complex.
AB  - Polypyrimidine tract binding protein (PTB) represses some alternatively spliced
      exons by direct occlusion of splice sites. In repressing the splicing of the c
      src N1 exon, we find that PTB acts by a different mechanism. PTB does not
      interfere with U1 snRNP binding to the N1 5' splice site. Instead, PTB prevents
      formation of the prespliceosomal early (E) complex across the intervening intron
      by preventing the assembly of the splicing factor U2AF on the 3' splice site of
      exon 4. When the unregulated 5' splice site of the upstream exon 3 is present,
      U2AF binding is restored and splicing between exons 3 and 4 proceeds in spite of
      the N1 exon bound PTB. Thus, rather than directly blocking the N1 splice sites,
      PTB prevents the 5' splice site-dependent assembly of U2AF into the E complex.
      This mechanism likely occurs in many other alternative exons.

PMID- 16109375
TI  - Mediator expression profiling epistasis reveals a signal transduction pathway
      with antagonistic submodules and highly specific downstream targets.
AB  - Mediator is an evolutionarily conserved coregulator of RNA polymerase II
      transcription. Microarray structure-function analysis of S. cerevisiae Mediator
      reveals functional antagonism between the cyclin-dependent kinase (Cdk) submodule
      and components from the Tail (Med15, Med2, Med3), Head (Med20, Med18), and Middle
      (Med31). Certain genes exhibit increased or decreased expression, depending on
      which subunit is deleted. Epistasis analysis with expression-profile phenotypes
      shows that MED2 and MED18 are downstream of CDK8. Strikingly, Cdk8-mediated
      modification of a single amino acid within Mediator represses the regulon of a
      single transcription factor, Rcs1/Aft1. Highly specific gene regulation is
      thought to be determined by activators and combinatorial use of cofactors. Here,
      subtle modification of the general transcription machinery through one of its own
      components is shown to determine highly specific expression patterns. Expression
      profiling can therefore precisely map regulatory cascades, and our findings
      support a role for Mediator as a direct processor of signaling pathways for
      determining specificity.

PMID- 16109376
TI  - The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and
      stimulates RNA polymerase II-dependent transcription.
AB  - Brd4 is a mammalian bromodomain protein that binds to acetylated chromatin.
      Proteomic analysis revealed that Brd4 interacts with cyclinT1 and Cdk9 that
      constitutes core positive transcription elongation factor b (P-TEFb). Brd4
      interacted with P-TEFb in the living nucleus through its bromodomain. About half
      of P-TEFb was bound to the inhibitory subunit and functionally inactive. Brd4
      interacted with P-TEFb that was free of the inhibitory subunit. An increase in
      Brd4 expression led to increased P-TEFb-dependent phosphorylation of RNA
      polymerase II (RNAPII) CTD and stimulation of transcription from promoters in
      vivo. Conversely, a reduction in Brd4 expression by siRNA reduced CTD
      phosphorylation and transcription, revealing that Brd4 is a positive regulatory
      component of P-TEFb. In chromatin immunoprecipitation (ChIP) assays, the
      recruitment of P-TEFb to a promoter was dependent on Brd4 and was enhanced by an
      increase in chromatin acetylation. Together, P-TEFb alternately interacts with
      Brd4 and the inhibitory subunit to maintain functional equilibrium in the cell.

PMID- 16109377
TI  - Recruitment of P-TEFb for stimulation of transcriptional elongation by the
      bromodomain protein Brd4.
AB  - The cyclinT1/Cdk9 heterodimer that constitutes core P-TEFb is generally presumed
      to be the transcriptionally active form for stimulating RNA polymerase II
      elongation. About half of cellular P-TEFb also exists in an inactive complex with
      the 7SK snRNA and the HEXIM1 protein. Here, we show that the remaining half
      associates with the bromodomain protein Brd4. In stress-induced cells, the
      7SK/HEXIM1-bound P-TEFb is quantitatively converted into the Brd4-associated
      form. The association with Brd4 is necessary to form the transcriptionally active
      P-TEFb, recruits P-TEFb to a promoter, and enables P-TEFb to contact the Mediator
      complex, a potential target for the Brd4-mediated recruitment. Although generally
      required for transcription, the P-TEFb-recruitment function of Brd4 can be
      substituted by that of HIV-1 Tat, which recruits P-TEFb directly for activated
      HIV-1 transcription. Brd4, HEXIM1, and 7SK are all implicated in regulating cell
      growth, which may result from their dynamic control of the general transcription
      factor P-TEFb.

PMID- 16109378
TI  - A deubiquitinating enzyme encoded by HSV-1 belongs to a family of cysteine
      proteases that is conserved across the family Herpesviridae.
AB  - We have discovered a ubiquitin (Ub)-specific cysteine protease encoded within the
      N-terminal approximately 500 residues of the UL36 gene product, the largest (3164
      aa) tegument protein of herpes simplex virus 1 (HSV-1). Enzymatic activity of
      this fragment, UL36USP, is detectable only after cleavage of UL36USP from full
      length UL36 and occurs late during viral replication. UL36USP bears no homology
      to known deubiquitinating enzymes (DUBs) or Ub binding proteins. Sequence
      alignment of the large tegument proteins across the family Herpesviridae
      indicates conservation of key catalytic residues amongst these viruses.
      Recombinant UL36USP exhibits hydrolytic activity toward Ub-AMC and ubiquitinated
      branched peptides in vitro. In addition, recombinant UL36USP can cleave polyUb
      chains and appears to be specific for Lys48 linkages. Mutation of the active site
      cysteine residue (Cys65) to alanine abolishes this enzymatic activity. The lack
      of homology between UL36USP and eukaryotic DUBs makes this new family of
      herpesvirus ubiquitin-specific proteases attractive targets for selective
      inhibition.

PMID- 16109379
TI  - The single-stranded genome of phage CTX is the form used for integration into the
      genome of Vibrio cholerae.
AB  - A major determinant of Vibrio cholerae pathogenicity, the cholera enterotoxin, is
      encoded in the genome of an integrated phage, CTXvarphi. CTXvarphi integration
      depends on two host-encoded tyrosine recombinases, XerC and XerD. It occurs at
      dif1, a 28 bp site on V. cholerae chromosome 1 normally used by XerCD for
      chromosome dimer resolution. The replicative form of the phage contains two pairs
      of binding sites for XerC and XerD in inverted orientations. Here we show that in
      the single-stranded genome of the phage, these sites fold into a hairpin
      structure, which creates a recombination target for XerCD. In the presence of
      XerD, XerC can catalyze a single pair of strand exchanges between this target and
      dif1, resulting in integration of the phage. This integration strategy explains
      why the rules that normally apply to tyrosine recombinase reactions seemed not to
      apply to CTXvarphi integration and, in particular, why integration is
      irreversible.

PMID- 16109380
TI  - Human origins of DNA replication selected from a library of nascent DNA.
AB  - The identification of metazoan origins of DNA replication has so far been
      hampered by the lack of a suitable genetic screening and by the cumbersomeness of
      the currently available mapping procedures. Here we describe the construction of
      a library of nascent DNA, representative of all cellular origin sequences, and
      its utilization as a screening probe for origin identification in large genomic
      regions. The procedure developed was successfully applied to the human 5q31.1
      locus, encoding for the IL-3 and GM-CSF genes. Two novel origins were identified
      and subsequently characterized by competitive PCR mapping, located approximately
      3.5 kb downstream of the GM-CSF gene. The two origins (GM-CSF Ori1 and Ori2) were
      shown to interact with different members of the DNA prereplication complex. This
      observation reinforces the universal paradigm that initiation of DNA replication
      takes place at, or in close proximity to, the binding sites of the trans-acting
      initiator proteins.

PMID- 16109381
TI  - Planners and their cognitive maps: an analysis of domain representations using
      multi dimensional scaling.
AB  - We expected planners working on the planning problems at a particular department
      for many years to have similar ideas about their work domain. However, we found
      the opposite when we analyzed the results of an extensive knowledge elicitation
      study we performed on 25 planners working in the rolling stock and rolling staff
      planning department of the Netherlands Railways (in Dutch: NS). The planners were
      asked to model their domain by means of card sorting and graph-positioning
      methods using domain-related objects and relations. When we applied multi
      dimensional scaling to the outcome of this study, we found large differences in
      the individual cognitive maps thus created. In this article, we describe the
      analyses and discuss our findings about planners' cognitive maps. These maps may
      have implications for the organization of planning in general, for training of
      planners, and for software design.

PMID- 16109382
TI  - Organizational climate in air traffic control Innovative preparedness for
      implementation of new technology and organizational development in a rule
      governed organization.
AB  - A positive and innovative organizational climate is of great importance in order
      to manage and adapt to change. Such a climate seldom evolves in organizations
      closely governed by rules and regulations. Because of ongoing organizational and
      technical changes within the Swedish Air Navigation Services Provider, a study
      concerning the organizational climate for changes and innovations was conducted
      to investigate the organization's capacity to cope with changes. Study locations
      were the two Swedish main air traffic control centers and parts of the civil
      aviation administration headquarters. In the study 390 subjects took part and the
      CCQ questionnaire was used to measure the organizational climate. The results
      show that the organizational climate is quite positive despite the rule-governed
      work. The results also show that administrative personnel assess the
      organizational climate as more positive than operative personnel. Comparisons
      between management positions did not result in any differences.

PMID- 16109383
TI  - Specific volumes of unsaturated phosphatidylcholines in the liquid crystalline
      lamellar phase.
AB  - The specific volumes of seven 1,2-diacyl-sn-glycero-3-phosphocholines with
      symmetric, unbranched acyl chains containing one, four, or six cis double bonds
      per chain, or with a saturated sn-1 chain and one, four, or six cis double bonds
      in the sn-2 chain were determined by the neutral buoyancy method. Experiments
      were conducted in the liquid crystalline lamellar phase over the temperature
      range from 5 to 35 degrees C. It is demonstrated that the molecular volume of
      phosphatidylcholines can be well approximated as the sum of a constant volume of
      the polar lipid head region and the temperature-dependent volumes of hydrocarbon
      chain CH2, CH, and terminal CH3 groups. A linear dependence of chain segment
      volumes on temperature was observed. A self-consistent set of partially
      temperature-dependent volumes is obtained that allows prediction of
      phosphatidylcholine molecular volumes within very tight error margins.

PMID- 16109384
TI  - The relationship between folate transport activity at low pH and reduced folate
      carrier function in human Huh7 hepatoma cells.
AB  - Transport of folates and antifolates in both hepatocytes and Huh7 human hepatoma
      cells is characterized by a low-pH optimum. Studies were undertaken to determine
      the extent to which this transport activity is mediated by the reduced folate
      carrier (RFC) in Huh7 human hepatoma cells. RFC expression was ablated by
      chemical mutagenesis and antifolate selective pressure with PT632 resulting in
      the PT632(R) subline in which RFC mRNA could not be detected. Methotrexate (MTX)
      influx in these cells at pH 7.4 was reduced by 70%, leaving substantial residual
      RFC-independent influx while influx of MTX and folic acid at pH 5.5 was not
      significantly decreased. The influx K(t) for folic acid and MTX at pH 5.5 in
      PT632(R) cells was 0.36 and 1.5 microM, respectively. The affinity of the low pH
      transporter in PT632(R) cells was highest for pemetrexed (K(i)=140 nM), very low
      for PT632 (K(i)=77 microM), and was stereospecific for the natural isomer (6S) of
      5-formyltetrahydrofolate. In Huh7 cells transiently transfected with an RFC
      siRNA, RFC expression was reduced by 60% resulting in a 40% decrease in MTX
      influx at pH 7.4 but only a very small (5%) reduction in MTX or folic acid influx
      at pH 5.5. These data indicate that MTX transport in Huh7 cells at neutral pH is
      mediated largely by RFC while at pH 5.5 the predominant route of transport is
      independent of RFC.

PMID- 16109385
TI  - Expression of PrP(C) in the rat brain and characterization of a subset of
      cortical neurons.
AB  - The cellular prion protein (PrP(C)) is a membrane-bound glycoprotein mainly
      present in the CNS. The scrapie prion protein (PrP(Sc)) is an isoform of PrP(C),
      and it is responsible for transmissible spongiform encephalopathies (TSEs), a
      group of neurodegenerative diseases affecting both humans and animals. The
      presence of the cellular form is necessary for the establishment and further
      evolution of prion diseases. Here, we map the regional distribution of PrP(C) in
      the rat brain and study the chemical nature of these immunopositive neurons. Our
      observations are congruent with retrograde transport of prions, as shown by the
      ubiquitous distribution of PrP(C) throughout the rat brain, but especially in the
      damaged areas that send projections to primarily affected nuclei in fatal
      familial insomnia. On the other hand, the presence of the cellular isoform in a
      subset of GABAergic neurons containing calcium-binding proteins suggests that
      PrP(C) plays a role in the metabolism of calcium. The lack of immunostaining in
      neurons ensheathed by perineuronal nets indicates that prions do not directly
      interact with components of these nets. The destruction of these nets is more
      likely to be the consequence of a factor needed for prions during the early
      stages of TSEs. This would cause destruction of these nets and death of the
      surrounded neurons. Our results support the view that destruction of this
      extracellular matrix is caused by the pathogenic effect of prions and not a
      primary event in TSEs.

PMID- 16109386
TI  - The enzymatic degradation and swelling properties of chitosan matrices with
      different degrees of N-acetylation.
AB  - In the design of chitosan-based drug delivery systems and implantable scaffolds,
      the biodegradation rate of the chitosan matrix represents a promising strategy
      for drug delivery and the function of carriers. In this study, we have
      investigated the degradation of chitosan with different degrees of N-acetylation,
      with respect to weight loss, water absorption, swelling behavior, molecular
      weight loss of bulk materials, and reducing sugar content in the media. Chitosan
      matrices were prepared by compression molding. The results revealed that the
      initial degradation rate, equilibrium water absorption, and swelling degree
      increased with decreasing degree of deacetylation (DD) and a dramatic rise began
      as DD of the chitosan matrix decreased to 62.4%. Chitosan matrices with DD of
      52.6%, 56.1%, and 62.4% had the weight half-life of 9.8, 27.3, and more than 56
      days, respectively, and the weight half-life of average molecular weight 8.4,
      8.8, and 20.0 days, respectively. For chitosan matrices with DD of 71.7%, 81.7%,
      and 93.5%, both types of half-life exceeded 84 days because of the much slower
      degradation rate. The dimension of chitosan matrices during degradation was
      determined by the process of swelling and degradation. These findings may help to
      design chitosan-based biomedical materials with predetermined degradation timed
      from several days to months and proper swelling behaviors.

PMID- 16109387
TI  - Glycosylation of acid sensitive acceptors. Synthesis of (2,3-epoxy-1-propyl)
      glycosides.
AB  - Treatment of O-benzylated derivatives of glycosyl N-allyl thiocarbamate with
      racemic or enantiomerically pure glycidol and bromine provides the 1,2-cis
      glycidyl glycosides. This protocol was mild, highly stereoselective and
      efficient.

PMID- 16109388
TI  - De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome
      in utero.
AB  - OBJECTIVE: We describe a genetic basis for atrial fibrillation and short QT
      syndrome in utero. Heterologous expression of the mutant channel was used to
      define the physiological consequences of the mutation. METHODS: A baby girl was
      born at 38 weeks after induction of delivery that was prompted by bradycardia and
      irregular rythm. ECG revealed atrial fibrillation with slow ventricular response
      and short QT interval. Genetic analysis identified a de novo missense mutation in
      the potassium channel KCNQ1 (V141M). To characterize the physiological
      consequences of the V141M mutation, Xenopus laevis oocytes were injected with
      cRNA encoding wild-type (wt) KCNQ1 or mutant V141M KCNQ1 subunits, with or
      without KCNE1. RESULTS: Ionic currents were recorded using standard two
      microelectrode voltage clamp techniques. In the absence of KCNE1, wtKCNQ1 and
      V141M KCNQ1 currents had similar biophysical properties. Coexpression of
      wtKCNQ1+KCNE1 subunits induced the typical slowly activating and voltage
      dependent delayed rectifier K(+) current, I(Ks). In contrast, oocytes injected
      with cRNA encoding V141M KCNQ1+KCNE1 subunits exhibited an instantaneous and
      voltage-independent K(+)-selective current. Coexpression of V141M and wtKCNQ1
      with KCNE1 induced a current with intermediate biophysical properties. Computer
      modeling showed that the mutation would shorten action potential duration of
      human ventricular myocytes and abolish pacemaker activity of the sinoatrial node.
      CONCLUSIONS: The description of a novel, de novo gain of function mutation in
      KCNQ1, responsible for atrial fibrillation and short QT syndrome in utero
      indicates that some of these cases may have a genetic basis and confirms a
      previous hypothesis that gain of function mutations in KCNQ1 channels can shorten
      the duration of ventricular and atrial action potentials.

PMID- 16109389
TI  - Tea catechins attenuate ventricular remodeling and graft arterial diseases in
      murine cardiac allografts.
AB  - OBJECTIVE: Tea catechins have many biological functions; these effects are
      induced by the suppression of several inflammatory factors. However, effects of
      catechins on cardiac allograft rejection have not been well investigated. METHODS
      AND RESULTS: To test the hypothesis that catechins can attenuate ventricular
      remodeling and graft arterial diseases (GAD) in cardiac rejection, we orally
      administered catechins to murine cardiac recipients. We analyzed the mechanisms
      using immunohistochemistry, RNase protection, gel mobility shift, and cell
      proliferation assays. Although severe myocardial cell infiltration, fibrosis, and
      GAD with enhancement of inflammatory factors were observed in untreated class II
      mismatch allografts at day 60, catechins attenuated these changes with altered
      Th1/Th2 cytokine balance and suppressed NF-kappaB activation and cell
      proliferation. CONCLUSION: Catechins are potent agents for the suppression of
      chronic rejection because they are critically involved in the suppression of
      proinflammatory signaling pathways.

PMID- 16109390
TI  - Retinoid status and responsiveness to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      in mice lacking retinoid binding protein or retinoid receptor forms.
AB  - We have investigated the role of Vitamin A (retinoid) proteins in hepatic
      retinoid processing under normal conditions and during chemical stress induced by
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a chemical known to interfere with
      retinoid turnover and metabolism. Three separate studies were performed in
      wildtype control mice and transgenic mice that lack one or more isoforms of
      retinoic acid receptors (RAR), retinoid X receptors (RXR), or intracellular
      retinoid-binding proteins (CRABP I, CRABP II, CRBP I). Body and organ weight
      development was monitored from 2 weeks of age to adult, and hepatic levels of
      retinyl esters, retinol, and retinoic acid were investigated. In addition,
      hepatic concentrations of 9-cis-4-oxo-13,14-dihydro-retinoic acid, a recently
      discovered retinoid metabolite that has proven sensitive to both TCDD exposure
      and Vitamin A status, were also determined. Mice absent in the three proteins
      CRBP I, CRABP I, and CRABP II (CI/CAI/CAII-/-) displayed significantly lower
      hepatic retinyl ester, retinol, and all-trans-retinoic acid levels compared to
      wildtype mice, whereas the liver concentrations of 9-cis-4-oxo-13,14-dihydro
      retinoic acid was considerably higher. After treatment with TCDD, hepatic total
      retinoids were almost entirely depleted in the CI/CAI/CAII-/- mice, whereas
      wildtype mice and mice lacking CRABP I, and CRABP II (CAI/CAII-/-) retained
      approximately 60-70% of their Vitamin A content compared to controls at 28 days.
      RAR and RXR knockout mice responded similarly to wildtype mice with respect to
      TCDD-induced retinoid disruption, with the exception of RXRbeta-/- mice which
      showed no decrease in hepatic Vitamin A concentration, suggesting that the role
      of RXRbeta in TCDD-induced retinoid disruption should be further investigated.
      Overall, the abnormal retinoid profile in the triple knockout mice (CI/CAI/CAII-/
      ), but not double knockout (CAI/CAII-/-) mice, suggests that a loss of CRBP I may
      account for the difference in retinoid profile in CI/CAI/CAII-/- mice, and is
      likely to result in an increased susceptibility to hepatic retinoid depletion
      following dioxin exposure.

PMID- 16109391
TI  - Surface properties of sulfur- and ether-linked phosphonolipids with and without
      purified hydrophobic lung surfactant proteins.
AB  - Two novel C16:0 sulfur-linked phosphonolipids (S-lipid and SO(2)-lipid) and two
      ether-linked phosphonolipids (C16:0 DEPN-8 and C16:1 UnDEPN-8) were studied for
      surface behavior alone and in mixtures with purified bovine lung surfactant
      proteins (SP)-B and/or SP-C. Synthetic C16:0 phosphonolipids all had improved
      adsorption and film respreading compared to dipalmitoyl phosphatidylcholine, and
      SO(2)-lipid and DEPN-8 reached maximum surface pressures of 72mN/m (minimum
      surface tensions of <1mN/m) in compressed films on the Wilhelmy balance (23
      degrees C). Dispersions of DEPN-8 (0.5mg/ml) and SO(2)-lipid (2.5mg/ml) also
      reached minimum surface tensions of <1mN/m on a pulsating bubble surfactometer
      (37 degrees C, 20cycles/min, 50% area compression). Synthetic lung surfactants
      containing DEPN-8 or SO(2)-lipid+0.75% SP-B+0.75% SP-C had dynamic surface
      activity on the bubble equal to that of calf lung surfactant extract (CLSE).
      Surfactants containing DEPN-8 or SO(2)-lipid plus 1.5% SP-B also had very high
      surface activity, but less than when both apoproteins were present together.
      Adding 10wt.% of UnDEPN-8 to synthetic lung surfactants did not improve dynamic
      surface activity. Surfactants containing DEPN-8 or SO(2)-lipid plus 0.75% SP
      B/0.75% SP-C were chemically and biophysically resistant to phospholipase A(2)
      (PLA(2)), while CLSE was severely inhibited by PLA(2). The high activity and
      inhibition resistance of synthetic surfactants containing DEPN-8 or SO(2)-lipid
      plus SP-B/SP-C are promising for future applications in treating surfactant
      dysfunction in inflammatory lung injury.

PMID- 16109392
TI  - Activity and expression of glutathione S-transferase pi in patients with
      amyotrophic lateral sclerosis.
AB  - Glutathione S-transferase (GST, EC 2.5.1.18) is an enzyme responsible for
      inactivation of a large variety of toxic, electrophilic compounds and organic
      peroxides. GST activity and GST pi expression were studied in patients with
      amyotrophic lateral sclerosis (ALS). Studies were conducted on cerebrospinal
      fluid (CSF), blood serum and peripheral blood mononuclear cells (PBMC) obtained
      from 40 ALS patients. CSF from 30 subjects without neurological diseases and
      blood from 40 healthy blood donors were used as controls. GST activity assayed
      with 1-chloro-2,4-dinitrobenzene (substrate for transferase activity) and cumene
      peroxide (substrate for peroxidase activity) was significantly decreased in PBMC
      of ALS patients, as well as the GST pi expression on both mRNA and protein level.
      The mean peroxidase activity was however significantly increased in CSF and serum
      of ALS patients with the specificity of 80% and 73%, and the sensitivity of 78%
      and 85%, respectively. It can thus be concluded that the protective barrier
      formed by GST is originally affected in peripheral blood of ALS patients, and may
      increase their vulnerability to toxic effects of electrophilic compounds and
      organic peroxides. Studies on a larger group are needed to answer the question
      whether GSH-Px determination may be implicated in the diagnosis of ALS.

PMID- 16109393
TI  - Neonate capillary blood gas reference values.
AB  - OBJECTIVES: Because biological data are instrument-dependent and because
      technology has evolved over the last two decades, the published capillary blood
      reference values for blood gases, lactate, ionized calcium (iCa) and glucose may
      not reflect the present day situation. Hence, we report such values for healthy
      term neonates at 48 +/- 12 h of life. DESIGN AND METHODS: The Institution Ethics
      Review Board for Research on Human Subjects has accepted the protocol. Extra
      blood sample was obtained at the time heel-pricks were performed in the frame of
      the Quebec genetic screening program. One hundred twenty-six term neonates (39.6
      +/- 1.2 weeks of gestation) were included in the study. pH, pO2, pCO2, lactate,
      ionized calcium and glucose were simultaneously measured with selective
      electrodes on the ABL 735 blood gas analyzer (Radiometer). RESULTS: All variables
      exhibited a Gaussian distribution. Since there was no gender effect, all data
      were pooled.

PMID- 16109394
TI  - Glycogen synthase kinase 3 controls endochondral bone development: contribution
      of fibroblast growth factor 18.
AB  - Glycogen synthase kinase 3 (GSK3) inhibits signaling pathways that are essential
      for bone development. To study the requirement for GSK activity during
      endochondral bone development, we inhibited GSK3 in cultured metatarsal bones
      with pharmacological antagonists. Interestingly, we find that inhibition of GSK3
      strongly repressed chondrocyte and perichondrial osteoblast differentiation.
      Moreover, chondrocyte proliferation was inhibited, whereas perichondrial cell
      proliferation was stimulated. These results mirror the effects of fibroblast
      growth factor signaling (FGF), suggesting the FGF expression is induced. Indeed,
      we showed that (1) FGF18 expression is stimulated following inhibition of GSK3
      and (2) GSK3 regulates FGF18 expression through the control of beta-catenin
      levels. Stimulation of cultured metatarsal with FGF18 had similar effects on the
      differentiation and proliferation of chondrocytes and perichondrial cells as GSK3
      repression. This suggests that the regulation of FGF18 expression is a major
      function of GSK3 during endochondral bone development. Consistent with this, we
      showed that the effect of GSK3 inhibition on chondrocyte proliferation is
      repressed in tissues lacking a receptor for FGF18, FGF receptor 3.

PMID- 16109395
TI  - Microarray analysis detects differentially expressed genes in the pharyngeal
      region of mice lacking Tbx1.
AB  - 22q11-deletion (DiGeorge/velocardiofacial) syndrome (22q11DS) is modeled by
      mutation of murine transcription factor Tbx1. As part of efforts to identify
      transcriptional targets of Tbx1, we analyzed the transcriptome of the pharyngeal
      region of Df1/+;Tbx1+/- embryos at 9.5 days of embryonic development using two
      independent microarray platforms. In this model, embryos are null for Tbx1, with
      hemizygosity of genes in cis with Tbx1 on one chromosome providing a positive
      control for array sensitivity. Reduced mRNA levels of genes deleted from Df1 were
      detected on both platforms. Expression level filtering and statistical analysis
      identified several genes that were consistently differentially expressed between
      mutant and wild type embryos. Real-time quantitative PCR and in situ
      hybridization validated diminished expression of Pax9 and Gcm2, genes known to be
      required for normal thymus and parathyroid gland morphogenesis, whereas Pax1,
      Hoxa3, Eya1, and Foxn1, which are similarly required, were not down-regulated.
      Gbx2, a gene required for normal arch artery development, was down-regulated
      specifically in the pharyngeal endoderm and the posterior part of pharyngeal arch
      1, and is a potential point of cross talk between the Tbx1 and Fgf8 controlled
      pathways. These experiments highlight which genes and pathways potentially
      affected by lack of Tbx1, and whose role may be explored further by testing for
      epistasis using mouse mutants.

PMID- 16109396
TI  - Fate-mapping of the epithelial seam during palatal fusion rules out epithelial
      mesenchymal transformation.
AB  - During palatogenesis, fusion of the palatine shelves is a crucial event, the
      failure of which results in the birth defect, cleft palate. The fate of the
      midline epithelial seam (MES), which develops transiently upon contact of the two
      palatine shelves, is still strongly debated. Three major mechanisms underlying
      the regression of the MES upon palatal fusion have been proposed: (1) apoptosis
      has been evidenced by morphological and molecular criteria; (2) epithelial
      mesenchymal transformation has been suggested based on ultrastructural and
      lipophilic dye cell labeling observations; and (3) migration of MES cells toward
      the oral and nasal areas has been proposed following lipophilic dye cell
      labeling. To verify whether epithelial-mesenchymal transformation of MES cells
      takes place during murine palatal fusion, we used the Cre/lox system to
      genetically mark Sonic hedgehog- and Keratin-14-expressing palatal epithelial
      cells and to identify their fate in vivo. Our analyses provide conclusive
      evidence that rules out the occurrence of epithelial-mesenchymal transformation
      of MES cells.

PMID- 16109397
TI  - The C. elegans Frizzled CFZ-2 is required for cell migration and interacts with
      multiple Wnt signaling pathways.
AB  - Members of the Frizzled family of integral membrane proteins are implicated in
      many developmental events, including specifying cell fate, orienting cell and
      planar polarity, and directing cell migration. Frizzleds function as cell surface
      receptors for secreted Wnt proteins. We report here the isolation of a mutation
      in cfz-2, a Caenorhabditis elegans Frizzled gene. Mutation of cfz-2 causes
      defective cell migration, disorganization of head neurons, and can cause ectopic
      axon outgrowth. Analysis of mosaic animals shows that CFZ-2 functions cell
      nonautonomously, but does not rule out an autonomous role. CFZ-2 is expressed
      primarily in the anterior of embryos and in several cells in the head of adults.
      Our analysis of interactions between CFZ-2 and other Wnt pathways reveals that
      three Wnts, CWN-1, CWN-2 and EGL-20, and a Frizzled, MOM-5, function redundantly
      with one another and with CFZ-2 for specific cell migrations. In contrast, CWN-1,
      CWN-2, EGL-20, CFZ-2, and MOM-5 antagonize one another for other migrations.
      Therefore, CFZ-2 functions by collaborating with and/or antagonizing other Wnt
      signaling pathways to regulate specific cell migrations.

PMID- 16109398
TI  - Gender and snow crab occupational asthma in Newfoundland and Labrador, Canada.
AB  - Fish and shellfish processing employs many thousands of people globally, with
      shellfish processing becoming more important in recent years. Shellfish
      processing is associated with multiple occupational health and safety (OHS)
      risks. Snow crab occupational asthma (OA) is work-related asthma associated with
      processing snow crab. We present a gender analysis of findings from a 3-year
      multifaceted study of snow crab OA in Newfoundland and Labrador, Canada. The
      study was carried out in four snow crab processing communities between 2001 and
      2004. An anonymous survey questionnaire on knowledge, beliefs, and concerns
      related to processing snow crab administered to 158 workers attending community
      meetings at the start of the research found that women were significantly more
      likely than men to associate certain health problems, especially chest tightness,
      difficulty breathing, and cough, with crab processing (P<0.001). Worker health
      assessments carried out with 215 processing workers (187 current/28 former; 120
      female/95 male) found that female participants were more likely to be diagnosed
      as almost certain/highly probable snow crab OA and allergy (P=0.001) and to be
      sensitized to snow crab (P=0.01) than male participants. Work histories from the
      health assessments were used to classify processing jobs as male or female.
      Allergen sampling (211 allergen samples: 115 area, 96 personal breathing zone)
      indicated that the plant areas where these male jobs were concentrated were
      associated with lower levels of aerosolized crab allergens (the agents
      responsible for OA to snow crab) than areas associated with female jobs. This
      difference was statistically significant in the two plants with poor ventilation
      (p<0.001 and P=0.017 for these plants). A gender analysis of work history data
      showed that female health assessment participants were likely to have worked
      longer processing snow crab than males (5 years versus 3.5 years, respectively).
      Cross-referencing of work history results with allergen sampling data for male
      and female job areas showed a gender difference in median cumulative exposures
      (duration of exposure x level of exposures) for health assessment participants.
      Health assessment participants with estimated higher median cumulative exposures
      were more likely to receive a diagnosis of almost certain/highly probable OA and
      allergy. Semistructured interviews with 27 health assessment participants (24
      female/ 3 male) with a diagnosis of almost certain/highly probable or possible
      snow crab OA indicated that these workers can experience substantial quality of
      life impacts while working and that they seek to reduce the economic impact of
      their illness by remaining at their jobs as long as possible. Indications of
      selection bias and other study limitations point to the need for more research
      exploring the relationship between the gender division of labor and knowledge,
      beliefs, and concerns about snow crab processing, as well as gender differences
      in prevalence, quality of life, and socioeconomic impact.

PMID- 16109399
TI  - Ethanol does not affect discriminative-stimulus effects of nicotine in rats.
AB  - The effects of ethanol were evaluated in rats trained to discriminate 0.4 mg/kg
      of nicotine from saline under a fixed-ratio 10 schedule of food delivery. Ethanol
      (0.1-1 g/kg, i.p.) did not produce any nicotine-like discriminative effects and
      did not produce any shift in the dose-response curve for nicotine discrimination.
      Thus, the ability to discriminate nicotine's effects does not appear to be
      altered by ethanol administration. However, the high dose of 1 g/kg ethanol,
      given either alone or in combination with nicotine, markedly depressed food
      maintained responding. This later effect was associated in some rats with an
      attenuation of the discriminative-stimulus effects of the training dose of
      nicotine. This suggests that previous reports of increased tobacco smoking
      following ethanol consumption in humans are connected, in some way, with an
      increase in motivation to consume nicotine that is produced by ethanol, rather
      than with a decrease in the subjective response to nicotine.

PMID- 16109400
TI  - Regulation of interleukin-6 secretion in murine pituicytes.
AB  - Pituicytes, the astrocytic glial cells of the neural lobe, are known to secrete
      interleukin-6 and nitric oxide upon stimulation with various inflammatory
      mediators, i.e. interleukin-1beta. Nitric oxide is described to modulate the
      secretion of interleukin-6 in various cell types. The aim of the present study
      was to investigate the effect of nitric oxide on interleukin-1beta induced
      interleukin-6 secretion. Furthermore the effect of interferon-gamma on
      interleukin-6 and nitric oxide release was investigated. Cultures of pituicytes
      were prepared of neural lobes from male mice. The effect of interleukin-1beta and
      interferon-gamma on interleukin-6 and nitric oxide secretion was investigated in
      pituicytes cultured for 14 days. The secretion of interleukin-6 and nitric oxide
      was determined after 24 h of stimulation. Pituicytes secrete interleukin-6 upon
      stimulation with interleukin-1beta dose dependently but did not induce any
      detectable nitric oxide release. Co-stimulation with interferon-gamma and
      interleukin-1beta induced a significant nitric oxide release. In addition
      interferon-gamma inhibits interleukin-1beta induced interleukin-6 secretion dose
      dependently. The observed effect of interferon-gamma on interleukin-6 secretion
      was not affected by the specific inducible nitric oxide synthase inhibitor 1400W
      (N-(3-[aminomethyl]benzyl)acetamidine). Furthermore interferon-gamma dose
      dependently inhibits unstimulated interleukin-6 secretion. Use of the nitric
      oxide releaser DETA/NO (2,2'-(hydroxynitrosohydrazono)bis-ethanimine)
      demonstrated that nitric oxide does not inhibit interleukin-1beta induced
      interleukin-6 secretion. These results demonstrated that nitric oxide has no
      influence on interleukin-1beta induced interleukin-6 secretion in cultured
      pituicytes. However the results are showing that interferon-gamma has an
      inhibitory effect on interleukin-6 secretion.

PMID- 16109401
TI  - Characterisation of imidazoline I2 binding sites in pig brain.
AB  - The imidazoline I2 binding sites in the central nervous system have previously
      been described in several different species including rat, mouse, rabbit and
      frog. The present study has investigated the imidazoline I2 binding site, and its
      relationship to the monoamine oxidase isoforms, in pig whole brain and compared
      the results obtained with data from other species. Results from saturation
      binding studies revealed that the imidazoline I2-selective ligand, [3H]2BFI (2-(2
      benzofuranyl)-2-imidazoline) labelled a single saturable population of sites with
      a KD=6.6 nM and Bmax=771.7 fmol/mg protein. The pharmacological characterisation
      of the sites was similar to that previously reported with a rank order of potency
      for the imidazoline I2 ligands of 2BFI>BU224>Idazoxan>BU226. Displacement by the
      imidazoline I1 ligands was low affinity and the monoamine oxidase inhibitors
      displaced with micromolar affinity. The majority of compounds displaced the
      binding in a monophasic manner, however, displacement by the putative endogenous
      ligand, harmane was biphasic. The relative populations of the two monoamine
      oxidase isoforms revealed a 10 fold greater expression of monoamine oxidase B
      relative to monoamine oxidase A. These data confirm the presence of imidazoline
      I2 binding sites in pig brain and show that their pharmacology is characteristic
      of that seen in other species. The proportion of monoamine oxidase A and B
      expressed in the pig brain is similar to that seen in the human brain therefore,
      given the association between imidazoline I2 binding sites and monoamine oxidase,
      the pig may provide a more useful model for human imidazoline I2 binding sites
      than other species such as the rat.

PMID- 16109402
TI  - Anti-allodynic interactions between NMDA receptor channel blockers and morphine
      or clonidine in neuropathic rats.
AB  - Previous studies suggested that combining N-methyl-d-aspartate (NMDA) receptor
      antagonists with either mu-opioid agonist morphine or alpha2-adrenoreceptor
      agonist clonidine results in the significant synergistic enhancement of analgesic
      activity in the animal models of acute and neuropathic pain. When given alone,
      NMDA receptor antagonists, morphine and clonidine are capable of attenuating
      tactile allodynia associated with chronic nerve injury. The present study aimed
      to assess anti-allodynic effects of these compounds and to test additivity of
      these interactions using isobolographic analysis. Adult male Wistar rats with
      unilateral loose ligation of sciatic nerve developed significant tactile
      allodynia (between-paw difference of about 18-20 g). In separate groups of
      animals, dose-dependent anti-allodynic activity was confirmed for memantine (1.8
      17.8 mg/kg), neramexane (1.8-17.8 mg/kg), morphine (1-10 mg/kg) and clonidine
      (0.01-0.1 mg/kg). In a subsequent series of experiments, memantine (or
      neramexane) and morphine (or clonidine) were co-administered at the fixed equi
      effective dose ratios (six dose levels per drug combination). None of the tested
      combinations produced supra-additive, synergistic effects. In fact,
      memantine+clonidine, neramexane+clonidine and morphine+neramexane were producing
      simple additive effects, while morphine+memantine was characterized as the infra
      additive combination. Thus, despite expectations based on previous studies, NMDA
      receptor channel blockers, memantine and neramexane, produce no synergistic
      interactions with either morphine or clonidine when administered acutely to rats
      with nerve injury-induced tactile allodynia.

PMID- 16109403
TI  - Effect of BU98008, an imidazoline1-binding site ligand, on body temperature in
      mice.
AB  - Previous studies using the novel imidazoline1-binding site ligand 1-(4,5-dihydro
      1H-imidazol-2-yl)isoquinoline hydrochloride, BU98008, have shown it induces a
      hypothermic response in rodents following intraperitoneal administration.
      Radioligand binding data has shown that BU98008 is a highly selective
      imidazoline1-binding site ligand with 300 fold selectively for the imidazoline1
      binding site relative to alpha2-adrenoceptors. However, alpha2-adrenoceptor
      agonists are known to induce hypothermia, therefore, the present study has
      investigated the ability of the selective alpha2-adrenoceptor antagonist,
      RX811059 (2-ethoxy idazoxan) and the mixed imidazoline1-binding site/alpha2
      adrenoceptor antagonist, efaroxan, to attenuate the BU98008-induced hypothermia.
      Preliminary experiments confirmed that BU98008 induced a dose-dependent decrease
      in body temperature in mice at 10 and 20 mg/kg. The response was not affected by
      pre-treatment with RX811059 but was significantly attenuated following pre
      treatment with efaroxan. These data suggest that BU98008-induced hypothermia is
      mediated by activation of imidazoline1-binding site. Body temperature may
      therefore provide a novel assay for investigating agonist and antagonist action
      at the imidazoline1-binding site.

PMID- 16109404
TI  - Multinucleated giant cell formation exhibits features of phagocytosis with
      participation of the endoplasmic reticulum.
AB  - Macrophage fusion leading to formation of multinucleated giant cells during
      chronic inflammation is poorly understood in mechanism and physiological
      significance. To address this, we developed a system of human macrophage fusion
      that utilizes IL-4, IL-13, or alpha-tocopherol to generate large foreign body
      type giant cells (FBGC). Extending our previously demonstrated requirements for F
      actin and mannose receptor (MR) activity, we find that macrophage fusion exhibits
      further features of a phagocytic process. Pharmacological inhibition of IL-4
      induced FBGC formation indicates critical roles for vacuolar-type ATPase,
      microtubules, the endoplasmic reticulum (ER), and calcium-independent
      phospholipase A(2) (iPLA(2)), but not calcium-dependent PLA(2) (cPLA(2)),
      secretory PLA(2) (sPLA(2)), cyclooxygenase, or lipoxygenase. Immunocytochemistry
      confirms iPLA(2) expression and absence of cPLA(2) or sPLA(2) expression in
      macrophages/FBGC. As markers of ER-mediated phagocytosis, calnexin and calregulin
      are detectable on non-permeabilized fusing macrophages and also concentrated at
      fusion interfaces where they co-localize with actin in permeabilized
      macrophages/FBGC. Furthermore, ER markers co-localize with concanavalin A
      reactivity on non-permeabilized fusing macrophages, suggesting that the ER may
      present MR ligand during fusion events. These data demonstrate for the first time
      that the mechanism of macrophage fusion leading to formation of multinucleated
      giant cells exhibits multiple features of phagocytosis with potential
      participation of the ER.

PMID- 16109405
TI  - Prolonged culture of endothelial cells and deposition of basement membrane modify
      the recruitment of neutrophils.
AB  - We tested whether endothelial cell conditioning during prolonged culture and
      deposition of basement membrane (BM) could modify neutrophil recruitment induced
      by the inflammatory cytokine, tumour necrosis factor-alpha (TNF). Confluent
      endothelial cells (EC) from human umbilical veins were cultured for 1 to 20 days
      and then stimulated with 1, 10 or 100 U/ml of TNF for 4 h. When isolated
      neutrophils were settled on EC stimulated with the lower doses of TNF, the levels
      of adhesion and the proportion of adherent cells that transmigrated increased
      markedly with time of culture. At 100 U/ml TNF, time of culture had little effect
      on recruitment, but the transmigrated neutrophils moved more slowly under the
      monolayer in longer-term cultures. The inhibitory effects of function-blocking
      antibodies against E-selectin and beta2-integrin, and studies in which
      neutrophils were perfused over short- or long-term cultures, suggested that
      increased adhesion and migration arose from increased efficiency of neutrophil
      activation by the EC. Prolonged culture was also associated with deposition of a
      distinct BM. When fresh EC were seeded on day 20 BM, transmigrated neutrophils
      moved more slowly under the EC than under control monolayers. Thus, EC change
      their pro-inflammatory phenotype during prolonged culture, and the deposited
      basement membrane influences neutrophil migration.

PMID- 16109406
TI  - Characterization of retinal damage in the episcleral vein cauterization rat
      glaucoma model.
AB  - Episcleral vein cauterization (EVC) is used in rats to generate a glaucoma model
      with high intraocular pressure (IOP). The long-term retinal damage in this
      glaucoma model, however, has not been accurately quantified. We report the
      location and amount of retinal ganglion cell (RGC) damage caused by (EVC) induced
      IOP elevation in two rat strains. IOP was raised in one eye of Wistar (N = 5) and
      Brown-Norway(B-N)(N = 7) rats by EVC and monitored monthly until IOP in
      contralateral eyes equalized at 5 months post-surgery. Animals were maintained
      for 3.5-4.5 additional months. B-N rats (N = 7) that had no EVC served as
      controls for this strain. Scotopic flash ERGs were recorded at baseline and just
      prior to euthanasia. Automated counts of all retrogradely labeled RGCs in retinal
      flat-mounts were determined and compared between contralateral eyes. RGC density
      maps were constructed and RGC size distribution was determined. Oscillatory
      potentials in the group of eyes which had elevated IOP were decreased at the time
      of euthanasia, when IOP had returned to normal. The group of normal B-N rats had
      similar RGC counts between contralateral eyes. In the experimental group the mean
      number of RGCs was not significantly different between control and experimental
      eyes, but 1 of 5 Wistar and 2 of 7 B-N experimental eyes had at least 30% fewer
      RGCs than contralateral control eyes. Total retinal area in B-N experimental eyes
      was higher compared to contralateral eyes. Cumulative IOP exposure of the
      experimental eyes was modestly correlated with RGC loss while oscillatory
      potentials appeared to be inversely related to RGC loss. In retinas with
      extensive (> 30% RGC loss) but not complete damage, smaller cells were preserved
      better than larger ones. The above results indicate that RGC loss in both Wistar
      and B-N strains is variable after a prolonged elevation of IOP via EVC. Such
      variability despite equivalent IOP levels and ERG abnormalities, suggests unknown
      factors that can protect IOP-stressed RGCs. Identification and enhancement of
      such factors could prove useful for glaucoma therapy.

PMID- 16109407
TI  - Molecular cloning of three zebrafish lin7 genes and their expression patterns in
      the retina.
AB  - The vertebrate retina develops from an undifferentiated sheet of neuroepithelial
      cells, whose differentiation requires the generation and maintenance of the
      correct cellular polarity. To examine the role of cell polarity in retinal
      development, we cloned three zebrafish lin7 genes (lin7a, lin7b, and lin7c),
      which each encodes a protein candidate that is required for
      generation/maintenance of neuroepithelial cell junctions. These three zebrafish
      Lin7 proteins share over 78% amino acid identity and contain both L27 and PDZ
      domains that are present in all Lin7 homologs. Immunoblots revealed that the
      Lin7b and Lin7c proteins were first expressed in the developing eye by 24hr
      postfertilization (hpf), while Lin7a was not detected in the eye until 72 hpf. At
      33 hpf, the Lin7 proteins localized at, or slightly apical of, the actin
      associated adherens junctions in the retinal neuroepithelium. This subcellular
      distribution required the expression of the Nok protein. In the absence of Nok,
      the Lin7 proteins failed to localize to either the ectopic adherens junctions or
      the cell membrane. At 4 days postfertilization, in situ hybridisation revealed
      that all three lin7 genes were expressed in both the ganglion cell layer and the
      bipolar cell region of the inner nuclear layer. The lin7a gene was also expressed
      in the amacrine and horizontal cell regions of the inner nuclear layer, while
      lin7c was also expressed in the outer nuclear layer. In the adult retina, where
      Lin7a is the predominant form expressed, the Lin7 proteins were localized to the
      outer and inner plexiform layers, the bipolar and horizontal cells of the inner
      nuclear layer, and the ganglion cells. These results suggest that the three
      zebrafish Lin7 proteins possess partially redundant, yet essential, roles in
      retinal development.

PMID- 16109408
TI  - Amniotic membrane induces apoptosis of interferon-gamma activated macrophages in
      vitro.
AB  - Amniotic membrane (AM) used as a temporary or permanent graft for ocular surface
      reconstruction has a potent anti-inflammatory effect. We would like to
      investigate the mechanism whereby AM induces macrophage apoptosis in vitro. Mouse
      macrophages, Raw 264.7 cells, were cultured on plastic, type I collagen, corneal
      stromal slice or AM stromal matrix in serum-free medium with or without
      interferon-gamma (IFN-gamma). Cells were stained by LIVE/DEAD assay, Hoechst
      33342, and TUNEL assay for cell death and apoptosis. Cell lysates and conditioned
      media were analysed by Cell Death Detection ELISA assay for quantitation of
      apoptosis. Conditioned media were also analysed by Griess assay for the nitrite
      concentration and ELISA assay for tumour necrosis factor alpha (TNF-alpha)
      concentration. Lysates of cells were subjected to Western blot analyses of IKK
      alpha, IKK-beta, p65 (RelA) subunit of nuclear factor kappaB (NF-kappaB), total
      Akt, phospho-Akt (Ser473), and phospho-FKHR (Thr24)/phosphor-FKHRL1 (Thr32). At
      48hr after cultivation, cells showed a low level of apoptosis when cultured on
      plastic, type I collagen and corneal stromal slice with or without IFN-gamma and
      on AM without IFN-gamma. Nevertheless, cells showed a significant increase of
      apoptosis when cultured on AM with IFN-gamma activation, and this phenomenon
      became apparent only after 48 hr. IFN-gamma-activated macrophages on plastic
      continuously produced nitric oxide (NO) and TNF-alpha during 72 hr culturing. In
      contrast, there was no NO and TNF-alpha production after 48 hr culture on AM. NO
      inhibitors, L-NMMA and L-NIL, attenuated NO production of IFN-gamma-activated
      macrophages on AM, while apoptosis was not decreased accordingly. Expression of
      IKK-alpha, IKK-beta, p65 (RelA) subunit of NF-kappaB total Akt, phosopho-Akt
      (Ser473), and phospho-FKHR (Thr24)/FKHRL1 (Thr32) was all down-regulated in IFN
      gamma-activated macrophages cultured on AM. In conclusion, AM stromal matrix
      induces apoptosis of IFN-gamma activated, but not non-activated macrophages, not
      through the generation of NO, but instead by down-regulating anti-apoptotic NF
      kappaB and Akt-FKHR signalling pathways.

PMID- 16109409
TI  - Myelinated and unmyelinated axons of the corpus callosum differ in vulnerability
      and functional recovery following traumatic brain injury.
AB  - Traumatic axonal injury (TAI), a common feature of traumatic brain injury, is
      associated with postinjury morbidity and mortality. However, TAI is not uniformly
      expressed in all axonal populations, with fiber caliber and anatomical location
      influencing specific TAI pathology. To study differential axonal vulnerability to
      brain injury, axonal excitability and integrity were assessed in the corpus
      callosum following fluid percussion injury in the rat. In brain slice
      electrophysiological recordings, compound action potentials (CAPs) were evoked in
      the corpus callosum, and injury effects were quantified separately for CAP
      waveform components generated by myelinated axons (N1 wave) and by unmyelinated
      axons (N2 wave). Ultrastructural analyses were also conducted of TAI-induced
      morphological changes in these axonal populations. The two populations of axons
      differed in response to brain injury, and in their functional recovery, during
      the first week postinjury. Amplitudes of N1 and N2 were significantly depressed
      at 3 h, 1 day, and 3 days survival. N1 amplitudes exhibited a recovery to control
      levels by 7 days postinjury. In contrast, N2 amplitudes were persistently
      suppressed through 7 days postinjury. Strength-duration properties of evoked CAPs
      further differentiated the effects of injury in these axonal populations, with N2
      exhibiting an elevated strength-duration time constant postinjury.
      Ultrastructural observations revealed degeneration of myelinated axons consistent
      with diffuse injury sequelae, as well as previously undocumented pathology within
      the unmyelinated fiber population. Collectively, these findings demonstrate
      differential vulnerabilities of axons to brain injury and suggest that damage to
      unmyelinated fibers may play a significant role in morbidity associated with
      brain injury.

PMID- 16109410
TI  - Effects of the perivascular space on convection-enhanced delivery of liposomes in
      primate putamen.
AB  - Convection-enhanced delivery has recently entered the clinic and represents a
      promising new therapeutic option in the field of neurodegenerative diseases and
      treatment of brain tumors. Understanding of the principles governing delivery and
      flow of macromolecules within the CNS is still poorly understood and requires
      more investigation of the microanatomy and fluid dynamics of the brain. Our
      previously established, reflux-free convection-enhanced delivery (CED) technique
      and real-time imaging MR method for monitoring CED delivery of liposomes in
      primate CNS allowed us to closely monitor infusions of putamen. Our findings
      indicate that CED in putamen is associated with perivascular transport of
      liposomes, throughout CNS arteries. The results may explain side effects seen in
      current clinical trials using CED. In addition, they clearly show the necessity
      for a monitoring technique for future direct delivery of therapeutic agents to
      the human central nervous system. Based on these findings, we believe that the
      physiological concept that the perivascular space serves as a conduit for
      distribution of endogenous molecules within the CNS also applies to
      interstitially infused agents.

PMID- 16109411
TI  - Cholinergic modulation of status epilepticus in the rat barrel field region of
      primary somatosensory cortex.
AB  - Status epilepticus (SE) represents a serious medical emergency that can produce
      long-lasting brain damage as well as cognitive and memory deficits. However, the
      mechanisms that determine the emergence of SE from a single seizure and the
      prolonged duration of SE are unknown. Therefore, we used pharmacological tools to
      investigate the cellular mechanisms that underlie this prolonged epileptic
      activity in the rat barrel field region of somatosensory cortex (S1BF).
      Electrocortical and unitary extracellular field recording in the rat S1BF region
      was used to assess abnormal epileptiform activity induced by intracerebral
      application of 4-aminopyridine (4-AP). Simultaneously, electromyographic (EMG)
      activity was recorded from mystacial pad musculature. Intracerebral injection of
      4-AP induced an SE that was paralleled by an increase of whisker activity that
      was not synchronized with the electrocortical recording. The seizures were
      originated ipsilaterally in the cortex of the injected hemisphere and propagated
      to the contralateral cortex with lower amplitude. The application of the
      glutamatergic NMDA receptor antagonist D (-)-2-amino-5-phosphonopentanoic acid
      (AP5) strongly increased the seizure-onset latency. The muscarinic receptor
      antagonist atropine changed the continuous rapid spiking pattern of SE to
      periodic discharges, while glutamatergic or GABAergic antagonist did not modify
      the electrographic features of SE. Our data suggest that the muscarinic
      cholinergic system plays an important role in the seizure modulation during SE in
      the somatosensory cortex, while their emergence is controlled, in part, by
      glutamatergic NMDA receptors.

PMID- 16109412
TI  - Inhibitory role of peroxiredoxin II (Prx II) on cellular senescence.
AB  - Reactive oxygen species (ROS) were generated in all oxygen-utilizing organisms.
      Peroxiredoxin II (Prx II) as one of antioxidant enzymes may play a protective
      role against the oxidative damage caused by ROS. In order to define the role of
      Prx II in organismal aging, we evaluated cellular senescence in Prx II(-/-) mouse
      embryonic fibroblast (MEF). As compared to wild type MEF, cellular senescence was
      accelerated in Prx II(-/-) MEF. Senescence-associated (SA)-beta-galactosidase
      (Gal)-positive cell formation was about 30% higher in Prx II(-/-) MEF. N-Acetyl-l
      cysteine (NAC) treatment attenuated SA-beta-Gal-positive cell formation. Prx II(
      /-) MEF exhibited the higher G2/M (41%) and lower S (1.6%) phase cells as
      compared to 24% and 7.3% [corrected] in wild type MEF, respectively. A high
      increase in the p16 and a slight increase in the p21 and p53 levels were detected
      in PrxII(-/-) MEF cells. The cellular senescence of Prx II(-/-) MEF was
      correlated with the organismal aging of Prx II(-/-) mouse skin. While
      extracellular signal-regulated kinase (ERK) and p38 activation was detected in
      Prx II(-/-) MEF, ERK and c-Jun N-terminal kinase (JNK) activation was detected in
      Prx II(-/-) skin. These results suggest that Prx II may function as an enzymatic
      antioxidant to prevent cellular senescence and skin aging.

PMID- 16109413
TI  - Mammalian mitochondria contain a soluble acyl carrier protein.
AB  - Plant and fungal mitochondria contain type II fatty acid synthesis systems
      closely related to those of bacteria in which the individual reactions are
      catalyzed by separate soluble proteins acting on intermediates bound to acyl
      carrier protein (ACP). Mammalian mitochondria are thought to synthesize fatty
      acids, but evidence for the key ACP component was lacking since the only reported
      ACP was the SDAP subunit of the membrane-bound NADH:ubiquinone oxidoreductase, We
      report that most of the SDAP is found in the soluble (matrix) fraction of bovine
      heart mitochondria and is therefore available to carry the intermediates of type
      II fatty acid synthesis.

PMID- 16109414
TI  - Heat stable ssDNA/RNA-binding activity of a wheat cold shock domain protein.
AB  - The cold-induced wheat WCSP1 protein belongs to the cold shock domain (CSD)
      protein family. In prokaryotes and eukaryotes, the CSD functions as a nucleic
      acid-binding domain. Here, we demonstrated that purified recombinant WCSP1 is
      boiling soluble and binds ss/dsDNA and mRNA. Furthermore, boiled-WCSP1 retained
      its characteristic nucleic acid-binding activity. A WCSP1 deletion mutant,
      containing only a CSD, lost ssDNA/RNA-binding activity; while a mutant containing
      the CSD and the first glycine-rich region (GR) displayed the activity. These data
      indicated that the first GR of WCSP1 is necessary for the binding activity but is
      not for the heat stability of the protein.

PMID- 16109415
TI  - A previously found thylakoid membrane protein of 14kDa (TMP14) is a novel subunit
      of plant photosystem I and is designated PSI-P.
AB  - We show that the thylakoid membrane phosphoprotein TMP14 is a novel subunit of
      plant photosystem I (PSI). Blue native/SDS-PAGE and sucrose gradient
      fractionation demonstrated the association of the protein exclusively with PSI.
      We designate the protein PSI-P. The presence of PSI-P subunit in Arabidopsis
      mutants lacking other PSI subunits was analyzed and suggested a location in the
      proximity of PSI-L, -H and -O subunits. The PSI-P protein was not differentially
      phosphorylated in state 1 and state 2.

PMID- 16109416
TI  - Oxytocin is associated with human trustworthiness.
AB  - Human beings exhibit substantial interpersonal trust-even with strangers. The
      neuroactive hormone oxytocin facilitates social recognition in animals, and we
      examine if oxytocin is related to trustworthiness between humans. This paper
      reports the results of an experiment to test this hypothesis, where trust and
      trustworthiness are measured using the sequential anonymous "trust game" with
      monetary payoffs. We find that oxytocin levels are higher in subjects who receive
      a monetary transfer that reflects an intention of trust relative to an
      unintentional monetary transfer of the same amount. In addition, higher oxytocin
      levels are associated with trustworthy behavior (the reciprocation of trust).
      Absent intentionality, both the oxytocin and behavioral responses are
      extinguished. We conclude that perceptions of intentions of trust affect levels
      of circulating oxytocin.

PMID- 16109417
TI  - The disappearing art of instrumental delivery: time to reverse the trend.
AB  - PURPOSE: This paper focuses attention on declining rates of instrumental (vacuum
      or forceps) delivery. The decline often means that women must travel further to
      deliver in hospitals with capacity for cesarean delivery. BACKGROUND: The paper
      illustrates recent trends in the use of vacuum extraction and forceps in low- and
      high-income countries. It describes some of the obstacles to the use of
      instrumental delivery and why the techniques, especially vacuum extraction,
      should be reintroduced. Over the past two decades, many countries have observed a
      decline in instrumental delivery rates while cesarean rates have increased.
      Objections to instrumental delivery are largely due to the potential harm it
      causes newborns. Some medical schools no longer train their professionals to
      perform instrumental delivery. Elsewhere, only specialists are permitted to
      perform the procedures. METHODS AND RESULTS: As this is a policy paper rather
      than a research report, the methods and results sections are not applicable.
      CONCLUSIONS: Vacuum extraction can be taught to midlevel practitioners (midwives,
      nurse practitioners and general physicians), thereby increasing access to
      emergency obstetric care especially at the periphery. This allows women to give
      birth closer to home in midlevel facilities when hospitals are not easily
      accessible or are overcrowded. Where instrumental and cesarean delivery are both
      available, instrumental delivery could potentially reduce the risks associated
      with cesarean delivery and reduce the costs of obstetric care.

PMID- 16109418
TI  - Fractalkine in the peritoneal fluid of women with endometriosis.
AB  - OBJECTIVE: The objective of this study was to evaluate the presence of
      fractalkine in the ascites and the association between fractalkine levels in the
      ascites and endometriosis. METHODS: Peritoneal fluids and peripheral blood
      samples were obtained from patients undergoing laparoscopy for infertility work
      up or laparoscopic cystectomy. Three samples of peritoneum were obtained from
      patients undergoing hysterectomy. Western blotting, RT-PCR and
      immunohistochemistry were performed. RESULTS: Fractalkine protein was detected in
      the ascites. Positive staining was confirmed in peritoneal surface cells and
      perivascular cells of the peritoneum. CX3CR1 positive cells were present in the
      cells in the peritoneal fluid. The fractalkine concentrations in the ascites of
      patients with endometriosis were lower than those without endometriosis. There
      was no significant difference between serum fractalkine levels in patients with
      and without endometriosis. CONCLUSION: The decreased level of fractalkine found
      in the peritoneal fluid of patients with endometriosis may contribute to the
      pathogenesis of endometriosis.

PMID- 16109419
TI  - Oral, vaginal and sublingual misoprostol for induction of labor.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of different administration
      routes of misoprostol for induction of labor. METHOD: PubMed, Cochrane Library
      and EMBASE searches were carried out using the keywords oral, vaginal,
      sublingual, buccal, misoprostol, labor induction, identifying randomized case
      controlled trials comparing different routes for giving misoprostol to induce
      labor, published in English between 1994 and 2004. RESULTS: Seventeen studies
      (3549 participants) were included. Compared to vaginal administration, oral
      misoprostol was associated with higher failure rates for achieving vaginal
      delivery within 24 h (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.23
      2.10), higher rates of uterine hyperstimulation without fetal heart rate (FHR)
      changes (OR 2.21, 95% CI 1.12-4.34) and lower cesarean section rates (OR 0.74,
      95% CI 0.56-0.97). A lower dose of oral misoprostol (50 microg) compared to the
      25-50 microg administered vaginally was associated with a higher rate of vaginal
      delivery not being achieved within 24 h (OR 3.60, 95% CI 2.10-6.18), more need
      for oxytocin augmentation (OR 2.19, 95% CI 1.65-2.92), less uterine
      hyperstimulation both without FHR changes (OR 0.58, 95% CI 0.42-0.80) and with
      FHR changes (OR 0.34, 95% CI 0.17-0.67) and fewer cesarean sections (OR 0.69, 95%
      CI 0.51-0.91). Compared to vaginal administration, buccal misoprostol resulted in
      a higher rate of failure to achieve vaginal delivery after 24 h, more frequent
      uterine hyperstimulation and lower rates of cesarean section, but these
      differences were not significant. When 50 mug of misoprostol used sublingually
      was compared to oral administration, the sublingual misoprostol was associated
      with less failure to achieve vaginal delivery after 24 h, less oxytocin
      augmentation and reduced cesarean section, but none of the differences were
      statistically significant. CONCLUSIONS: Vaginal misoprostol appears more
      effective than the equivalent dosage administered orally. However, the vaginal
      route appears to be associated with a higher risk of uterine hyperstimulation.
      Sublingual misoprostol seems an effective route of administration, but a lack of
      data necessitates more clinical trials to establish the effectiveness and safety
      of the buccal/sublingual route.

PMID- 16109420
TI  - Correlates of perceived autonomy among elders in a senior citizen home: a cross
      sectional survey.
AB  - BACKGROUND: Researchers have pointed out several factors that correlated with or
      influenced autonomy in older people. However, these studies covered only a range
      of socio-demographic or physical factors, while factors from psychosociological
      and spiritual domains remain ignored. Also, there is lack of quantitative
      research and publications in this area. OBJECTIVES: To explore factors related to
      autonomy among elders in a senior citizen home. DESIGN: A cross-sectional design
      utilizing a correlational approach was adopted. PARTICIPANTS: A stratified random
      sample of 121 subjects older than 64 years was recruited at a senior citizen
      home. METHODS: Questionnaires and interviews were used to collect data. The
      structured questionnaire consisted of five parts, each gauging socio-demographic
      information, life attitudes, frequency and satisfaction of social support, and
      autonomy. Descriptive and stepwise multiple linear regression analysis were used
      to analyze the data. FINDINGS: Subjects had a high autonomy score (mean = 3.63),
      with the greatest score in independence (mean = 4.39), followed by individuality
      (mean = 3.74) and freedom (mean = 3.22). Multiple regression analysis showed that
      satisfaction of social support (beta = .57), functional ability (beta = .25),
      life attitudes (beta = .20), and level of education (beta = .14) significantly
      affected autonomy in these elderly subjects and explained 64.2% of the total
      variance of autonomy in this population. CONCLUSIONS: Findings from this study
      indicate that perceived autonomy is influenced by social support, functional
      ability, life attitude, and literacy among institutionalized elders.

PMID- 16109421
TI  - CD16 polymorphisms and NK activation induced by monoclonal antibody-coated target
      cells.
AB  - CD16 and natural killer (NK) cells appear to play a central role in mediating the
      anti-tumor effects of monoclonal antibody (mAb) therapy, yet little is known
      about changes in NK cells that result from interaction of the NK cells with mAb
      coated tumor cells under physiologic conditions. We developed a system using
      peripheral blood mononuclear cells (PBMCs) and either transformed B cells or
      breast cancer cells to assess how mAbs impact on NK cell phenotype. Rituximab,
      apolizumab and trastuzumab induced modulation of CD16 and upregulation of CD54 on
      NK cells when the appropriate target cells were present. Higher concentrations of
      mAb were needed to induce these changes on NK cells from subjects with the lower
      affinity CD16 polymorphism. Phenotypic changes were greater in NK cells from
      subjects with the higher affinity polymorphism even when saturating
      concentrations of mAb were used, demonstrating increased concentration of mAb can
      overcome some, but not all, of the influence CD16 polymorphisms have on NK
      activation. These studies provide a straightforward and easily reproducible
      technique to measure the ability of mAb-coated tumor cells to activate NK cells
      in vitro which should be particularly useful as mAbs with varying affinity for
      both target antigen and Fc receptor (FcR) are developed.

PMID- 16109422
TI  - Efficient production of complement (C3d)3 fusion proteins using the baculovirus
      expression vector system.
AB  - Proteins fused to activated complement (C) fragments elicit enhanced
      immunogenicity. This "natural adjuvant" effect may have important implications
      when considering novel vaccination approaches. Here we describe both the
      construction of a novel fusion protein, consisting of a well characterized test
      antigen fused to multiple copies of the activated complement component (C3d)3, as
      well as an efficient method for its expression and production in insect cells.
      Using the inherent biological advantages of the baculovirus expression system, as
      well as applying specific infection and harvesting modifications, we have
      optimized the efficiency of protein production. Our modifications allow
      purification of fusion proteins directly from cell supernatant in a single anion
      exchange chromatographic step. This alleviates the requirement for the inclusion
      of protein affinity tags. The integrity of the purified recombinant protein was
      evaluated by SDS PAGE analysis, reactivity with antibodies, as well as in vivo by
      administration as an immunogen.

PMID- 16109423
TI  - Structural snapshots of MTA/AdoHcy nucleosidase along the reaction coordinate
      provide insights into enzyme and nucleoside flexibility during catalysis.
AB  - MTA/AdoHcy nucleosidase (MTAN) irreversibly hydrolyzes the N9-C1' bond in the
      nucleosides, 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (AdoHcy) to
      form adenine and the corresponding thioribose. MTAN plays a vital role in
      metabolic pathways involving methionine recycling, biological methylation,
      polyamine biosynthesis, and quorum sensing. Crystal structures of a wild-type
      (WT) MTAN complexed with glycerol, and mutant-enzyme and mutant-product complexes
      have been determined at 2.0A, 2.0A, and 2.1A resolution, respectively. The WT
      MTAN-glycerol structure provides a purine-free model and in combination with the
      previously solved thioribose-free MTAN-ADE structure, we now have separate apo
      structures for both MTAN binding subsites. The purine and thioribose-free states
      reveal an extensive enzyme-immobilized water network in their respective binding
      subsites. The Asp197Asn MTAN-MTA and Glu12Gln MTAN-MTR.ADE structures are the
      first enzyme-substrate and enzyme-product complexes reported for MTAN,
      respectively. These structures provide representative snapshots along the
      reaction coordinate and allow insight into the conformational changes of the
      enzyme and the nucleoside substrate. A "catalytic movie" detailing substrate
      binding, catalysis, and product release is presented.

PMID- 16109424
TI  - The kinetic basis for dual recognition in colicin endonuclease-immunity protein
      complexes.
AB  - The antibacterial activity of E colicin endonucleases (DNases) is counteracted by
      the binding of immunity proteins; the affinities of cognate and non-cognate
      complexes differing by up to ten orders of magnitude. Here, we address the
      mechanism of complex formation using a combination of protein engineering, pre
      steady-state kinetics and isothermal titration calorimetry, in order to
      understand the underlying basis for specificity. Contrary to previous work, we
      show that a pre-equilibrium mechanism does not explain the binding kinetics.
      Instead, the data are best explained by a modified induced-fit mechanism where
      cognate and non-cognate complexes alike form a non-specific, conformationally
      dynamic encounter complex, most likely centred on conserved interactions at the
      interface. The dynamics appear to be an intrinsic property of the encounter
      complex where the proteins move relative to one another, thereby sampling
      different conformations rather than being "induced" by binding. This allows
      optimal alignment of interface specificity sites, without producing energetically
      costly conformational changes, essential for high-affinity binding. Importantly,
      specificity is achieved without slowing the rate of association, an important
      requirement for rapid inhibition of the colicin in the producing bacterial cell.
      A rigid-body rotation model is also consistent with the observation that
      specificity contacts in colicin-immunity protein complexes can involve different
      regions of the interface. Such a kinetic discrimination mechanism explains the
      ability of DNase-specific immunity proteins to display dual recognition
      specificity, wherein they are broadly cross-reactive yet are highly specific,
      achieving femtomolar binding affinities in complexes with their cognate DNases.

PMID- 16109425
TI  - Energetics of binding the mammalian high mobility group protein HMGA2 to poly(dA
      dT)2 and poly(dA)-poly(dT).
AB  - The mammalian high mobility group protein A2 (HMGA2) is a chromosomal
      architectural transcription factor involved in oncogenesis and cell
      transformation. It has three "AT-hook" DNA binding domains, which specifically
      bind to the minor groove of AT DNAs. The interaction of HMGA2 with poly(dA-dT)2
      and poly(dA)poly(dT) has been investigated using the ethidium displacement assay,
      isothermal titration calorimetry, and UV melting studies. Each AT hook DNA
      binding domain was found to bind to 5 bp and each HMGA2 molecule binds to 15 bp.
      Although an individual AT hook DNA binding domain binds to AT DNAs with moderate
      affinity, HMGA2 binds with very high affinity to both DNAs in solutions
      containing 20 mM Na+ at 25 degrees C. The K(a) and binding enthalpy for poly(dA
      dT)2 were determined to be, respectively, 1.9x10(14)M(-1) and -29.1(+/
      0.5)kcal/mol. The binding reaction is enthalpy-driven with a favorable free
      energy of -19.5 kcal/mol and unfavorable entropy of -32.5 cal/mol K (-TDeltaS=
      +9. 7kcal/mol) at a 1M reference state. Interestingly, although HMGA2 binds to
      poly(dA)poly(dT) with a binding constant of 9.6x10(12) M(-1), the binding
      reaction is entropy-driven with an unfavorable enthalpy of +0.6 kcal/mol, a free
      energy of -17.7 kcal/mol and an entropy of +61.4 cal/mol K (-TDeltaS=-18.3
      kcal/mol) at the 1 M state. The enthalpy-entropy compensation is similar to that
      of several minor groove-binding drugs such as netropesin, distamycin A and
      Hoechst33258 and may be a reflection of dehydration difference of different
      ligand-DNA complexes. The salt-dependence of the binding constant of HMGA2 with
      both DNAs showed that electrostatic interaction is a dominant force for the
      binding reactions. The temperature dependence of binding enthalpy for poly(dA
      dT)2 indicates a large heat capacity of binding of -705(+/-113) cal/molK,
      consistent with an important role of solvent displacement in the linked
      folding/binding processes in this system.

PMID- 16109426
TI  - Individual and health-related quality of life assessment in amyotrophic lateral
      sclerosis patients and their caregivers.
AB  - We performed a cross-sectional study aimed to address the quality of life (QoL)
      and putative associated variables in amyotrophic lateral sclerosis (ALS) patients
      and their respective caregivers, using both health-related (WHOQOL-BREF) and
      individual (SEIQoL-DW) QoL instruments. Further, we sought to investigate
      concordance within patient-caregiver pairs for ratings of respective QoL. Thirty
      seven patient-caregiver pairs were included in the study. QoL was rated low by
      both patients and caregivers, and there was no significant difference between
      them on scores of overall QoL, even if caregivers showed higher scores on the
      physical and psychological WHOQOL-BREF domains compared to patients. No
      correlation could be found between QoL of both patients and caregivers and all
      the examined socio-demographic variables. Moreover, concordance between patients
      and respective caregivers was low for ratings of QoL, suggesting that their QoL
      is not necessarily interrelated, and that these couples do not actually represent
      a unique psychological entity. Interestingly, physical dysfunction, measured with
      the ALS-FRS, was not significantly correlated with caregivers' individual QoL
      scores. The most frequently nominated SEIQoL-DW cues were related to health
      (physical and psychological) and family for both patients and caregivers, and
      there was high agreement for the choice of areas important for subject's QoL.
      Interestingly, patients and caregivers who endorsed spirituality as a significant
      domain reported better QoL. Our study confirms that ALS has a negative impact on
      QoL in both patients and caregivers. However, caregivers who present lower QoL
      levels are not always those who have to look after the most physically or
      psychologically impaired patients. Major attention on QoL issues of both patients
      and caregivers, family status, and health perception, integrated with the medical
      evaluation, could lead to a better understanding of the problems related to the
      caregiving experience, and could help couples dealing with this life-threatening
      disease.

PMID- 16109427
TI  - Late-onset pure cerebellar ataxia: differentiating those with and without
      identifiable mutations.
AB  - Late onset cerebellar ataxia can be caused by several genetic mutations but a
      large percentage of patients remain undiagnosed. Thirty-eight patients with onset
      of slowly progressive, pure cerebellar ataxia >or=40 years-of-age were identified
      from a large ataxia database. Their clinical findings and quantitative oculomotor
      tests were reviewed; all were screened for SCA1, SCA2, SCA3, SCA6, SCA8, SCA14,
      and the Fragile X premutation (FMR1). All 47 exons of CACNA1A were screened for
      mutations. Genetic analysis uncovered a mutation in 11 patients. The SCA6
      mutation was present in 8 patients (repeats 22-23). Three additional genetic
      mutations were found: SCA1 (42 repeats), SCA3 (66 repeats), and SCA8 (121
      repeats). Patients without identified genetic mutations were characterized by 1)
      a later age of onset, 2) truncal without extremity ataxia, 3) and down beat
      nystagmus. Although only a third of these idiopathic late onset ataxia patients
      had a positive family history, this homogeneous syndrome probably represents a
      yet to be identified genetic disorder.

PMID- 16109428
TI  - 'Importance sampling' in MS: use of diffusion tensor tractography to quantify
      pathology related to specific impairment.
AB  - Specific neurological impairments in multiple sclerosis (MS) are dependent on the
      pathology in clinically eloquent areas of the central nervous system. We aimed to
      use diffusion tensor fiber tracking to identify the pyramidal tracts and corpus
      callosum in MS patients, measure the apparent diffusivity within the tracts, and
      evaluate whether this would correlate with relevant disability scores. Dual-echo
      and diffusion tensor magnetic resonance imaging (DT-MRI) brain scans were
      obtained from 29 patients with relapsing remitting MS, and 13 age and gender
      matched normal controls. Voxels from pyramidal tracts and corpus callosum were
      automatically identified using a tractography based algorithm. Mean apparent
      diffusion coefficient (ADC(av)) was measured for these tracts. Scores of Expanded
      Disability Status Scale (EDSS) and Paced Auditory Serial Addition Test (PASAT)
      were obtained. The median EDSS score was 2.5 (inter-quartile range 2-3.25). The
      ADC(av) in the pyramidal tracts (p=0.02) and corpus callosum (p=0.0004) in
      patients was significantly higher than in controls. Pyramidal tracts ADC(av) was
      correlated with pyramidal FSS (r=0.5, p=0.008). Corpus callosum ADC(av) was
      correlated with PASAT (r=-0.58, p=0.001). Global T2 lesion volume did not
      correlate with the EDSS, but correlated with ADC(av) of the pyramidal tracts
      (r=0.6, p=0.0007) and corpus callosum (r=0.8, p<0.0001). T2 lesion volume within
      the pyramidal tracts and corpus callosum correlated with ADC(av) in the pyramidal
      tracts (r=0.6, p=0.0009) and corpus callosum (r=0.65, p=0.0002) respectively, but
      not with pyramidal FSS or PASAT score. DT-MRI quantifies pathology in specific
      white matter tracts and may increase the specificity of MRI in monitoring
      progression of motor and cognitive deficits in MS.

PMID- 16109429
TI  - Lymphocyte-specific protein tyrosine kinase is a novel risk gene for Alzheimer
      disease.
AB  - Lymphocyte-specific protein tyrosine kinase (LCK) is a lymphoid-specific, Src
      family protein tyrosine kinase that is known to play a pivotal role in T-cell
      activation and interact with the T-cell coreceptors, CD4 and CD8. It has been
      shown to be significantly down-regulated in Alzheimer disease (AD) hippocampus
      compared with non-demented controls. Furthermore, it is located in a previously
      identified genetic linkage region (1p34-36) associated with AD. Therefore, we
      consider it to be a candidate gene for AD. We examined the relationship between
      AD and the LCK and apolipoprotein E (APOE) genes in 376 AD (including 323 late
      onset AD (LOAD) cases and 53 early-onset AD (EOAD) cases) and 378 non-demented
      controls using a single nucleotide polymorphism (SNP). The polymorphism in intron
      1 (+6424 A/G) was significantly associated with AD risk. The odds ratio (OR) for
      total AD associated with the GG genotype was 1.41 (95% CI=1.06-1.87) and that for
      LOAD was 1.37 (95%CI=1.02-1.85), while that for APOE-epsilon4 was 5.06 (95%
      CI=3.60-7.12). In the APOE-epsilon4 non-carrier subgroup, the GG genotype also
      showed significant association (OR=1.66; 95% CI=1.16-2.38). These results
      indicate that the LCK is a novel risk gene for AD regardless of the APOE
      genotype.

PMID- 16109430
TI  - Cannabinoid signalling.
AB  - After their discovery, the two known cannabinoid receptors, CB(1) and CB(2), have
      been the focus of research into the cellular signalling mechanisms of
      cannabinoids. The initial assessment, mainly derived from expression studies, was
      that cannabinoids, via G(i/o) proteins, negatively modulate cyclic AMP levels,
      and activate inward rectifying K(+) channels. Recent findings have complicated
      this assessment on different levels: (1) cannabinoids include a wide range of
      compounds with varying profiles of affinity and efficacy at the known CB
      receptors, and these profiles do not necessarily match their biological activity;
      (2) CB receptors appear to be intrinsically active and possibly coupled to more
      than one type of G protein; (3) CB receptor signalling mechanisms are diverse and
      dependent on the system studied; (4) cannabinoids have other targets than CB
      receptors. The aim of this mini review is to discuss the current literature
      regarding CB receptor signalling pathways. These include regulation of adenylyl
      cyclase, MAP kinase, intracellular Ca(2+), and ion channels. In addition, actions
      of cannabinoids that are not mediated by CB(1) or CB(2) receptors are discussed.

PMID- 16109431
TI  - Comparative effect of seeds of Rhynchosia volubilis and soybean on MG-63 human
      osteoblastic cell proliferation and estrogenicity.
AB  - The seeds of Rhynchosia volubilis (SRV) (Leguminosae) and soybean have been used
      in oriental folk medicine to prevent postmenopausal osteoporosis. Their
      beneficial effects are caused by a high content of isoflavone, which function as
      partial agonists or antagonists of estrogen. To compare the estrogenic effects of
      SRV and soybean on the MG-63 osteoblastic cell proliferation, 70% methanol
      extracts of SRV or soybean were treated on MG-63 cells. Although biphasic over a
      concentration range of 0.001 mg/ml-0.1 mg/ml, both SRV and soybean extracts
      increased MG-63 cell proliferation. However SRV was more effective at increasing
      the cell proliferation that paralleled with the greater estrogenic effects as
      determined by estrogen receptor alpha (ERalpha) expression, an estrogenic
      response element (ERE)-luciferase activity and the selective expression of
      insulin-like growth factor-I (IGF-I). SRV-induced IGF-I expression resulted from
      increases in the mRNA levels. Despite the increased expression of ERbeta, ERE
      activity and IGF-I expression by soybean were lower than those by SRV.
      Furthermore, the comparable estrogenic effects between SRV and the combined
      treatment of genistein and daidzein standards at 0.5 x 10(-8) M, which is a
      concentration of these two isoflavones similar to that of SRV at 0.001 mg/ml,
      demonstrate that the greater estrogenicity of SRV for MG-63 cell proliferation is
      mediated by the synergism of low levels of isoflavones for the selective
      expression of IGF-I.

PMID- 16109432
TI  - Synergistic anti-inflammatory interaction between meloxicam and aminoguanidine
      hydrochloride in carrageenan-induced acute inflammation in rats.
AB  - Interaction studies with inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) inhibitor have been conducted to assess the nature of
      interaction and the possible therapeutic advantage. The interaction between
      meloxicam--a selective COX-2 inhibitor--and aminoguanidine hydrochloride--a
      selective iNOS inhibitor-- was examined in carrageenan-induced paw edema in rats.
      Appropriate statistical method was applied to detect the nature of anti
      inflammatory interaction. Different doses of meloxicam (1, 3, 10 and 30 mg/kg) or
      aminoguanidine hydrochloride (10, 30, 100 and 300 mg/kg) were administered orally
      to adult male albino rats. Higher doses of meloxicam (3, 10 and 30 mg/kg) showed
      statistically significant anti-inflammatory effect. However, aminoguanidine
      hydrochloride did not show any anti-inflammatory activity. Combination of sub
      threshold dose of meloxicam (1 mg/kg) with increasing doses of aminoguanidine
      hydrochloride (30, 100 and 300 mg/kg) resulted in synergistic anti-inflammatory
      effect. Combined therapy with sub-threshold dose of aminoguanidine hydrochloride
      (30 mg/kg) with increasing doses of meloxicam (1, 3, 10 and 30 mg/kg) also
      resulted in synergistic anti-inflammatory effect. The possible mechanism of
      interaction could be the stimulation of COX-2 activity by nitric oxide (NO) by
      combining with heme component. These results suggest that co-administration of
      meloxicam and aminoguanidine hydrochloride may be an alternative in clinical
      control of inflammation.

PMID- 16109433
TI  - Relationships between genomic, cell cycle, and mutagenic responses of TK6 cells
      exposed to DNA damaging chemicals.
AB  - Genotoxic stress causes a variety of cellular and molecular responses in
      mammalian cells, including cell cycle arrest, DNA repair, and apoptosis. These
      responses result from the interplay between the genotoxic events themselves, and
      the biological context in which they occur. To better understand this interplay,
      we investigated cytotoxicty, mutagenesis, cell cycle profile, and global gene
      expression in the human TK6 lymphoblastoid cell line exposed to six
      genotoxicants. The six compounds have broad structural diversity and cause
      genotoxic stress by many different mechanisms, including covalent modification
      (methyl methanesulfonate, mitomycin C), reactive oxygen species (hydrogen
      peroxide, bleomycin), and topoisomerase II inhibition (etoposide and
      doxorubicin). Cell cycle analysis was performed 4 and 20 h following a 4 h
      chemical exposure. Cells exposed to all compounds experienced S-phase arrest at
      the 8h time point, but by 24 h had markedly different cell cycle responses. Cells
      exposed to compounds that cause covalent modification had a strong G2/M arrest at
      24 h. These cells also had a robust (>25-fold) increase in mutant frequency, and
      had a moderate but sustained p53 response at 4, 8, and 24h, detectable as
      approximately 2-5-fold increases in transcript levels for p21WAF1/CIP1,
      GADD45alpha, BTG2, and cyclin G1. In contrast, cells exposed to the reactive
      oxygen compounds had little or no G2/M arrest at 24 h and no increase in mutant
      frequency. In addition, these compounds caused a strong but transient induction
      of the p53 pathway, detectable as 15-25-fold increases in p21WAF1/CIP1
      transcription at 4 h that decreased dramatically by 8h and was near control
      levels at 24 h. Thus, the mutagenic effect of compounds was consistent with G2/M
      arrest and sustained kinetics of p53 pathway activation. Global gene expression
      data were also consistent with the mutagenesis data. Activation of genes
      associated with cell cycle arrest, the p53 and TNF-related pathways, and
      chemokines and chemokine receptors, were particularly evident for the reactive
      oxygen compounds. In contrast, the most mutagenic compounds caused fewer and less
      robust changes in global gene expression. There was therefore an inverse
      relationship between global gene expression and mutagenic potency.

PMID- 16109434
TI  - Enhanced cellular immunity to SIV Gag following co-administration of adenoviruses
      encoding wild-type or mutant HIV Tat and SIV Gag.
AB  - Among candidate antigens for human immunodeficiency virus (HIV) prophylactic
      vaccines, the regulatory protein Tat is a critical early target, but has a
      potential for immune suppression. Adenovirus (Ad) recombinants encoding wild-type
      HIV Tat (Tat-wt) and a transdominant negative mutant HIV Tat (Tat22) were
      constructed and administered to mice separately or together with Ad-SIVgag.
      Immunogenicity and effects on immune responses to the co-administered Gag
      immunogen were evaluated. Wild-type and mutant Tat recombinants elicited similar
      Tat-specific cellular and humoral immune responses. Co-administration of either
      Tat immunogen with Ad-SIVgag induced modest but significant enhancement of Gag
      specific interferon-gamma secreting T cells and lymphoproliferative responses.
      Neither the Ad-recombinant encoding Tat-wt nor Tat22 suppressed induction of anti
      Tat or anti-Gag antibodies. Based on the immune responses observed in mice, both
      recombinants appear to be suitable vaccine candidates. Their contribution to
      protective efficacy remains to be determined in a non-human primate model.

PMID- 16109435
TI  - The role of varroa mites in infections of Kashmir bee virus (KBV) and deformed
      wing virus (DWV) in honey bees.
AB  - To determine the roles of varroa mites in activating or vectoring viral
      infections, we performed quantitative comparison of viral infections between bees
      with and without mites by dot blot analysis and enzyme-linked immunosorbent assay
      (ELISA). Under natural and artificial mite infestations, bee pupae contained
      significantly higher levels of Kashmir bee virus (KBV) and deformed wing virus
      (DWV) RNAs and KBV structural proteins than mite-free pupae. Moreover, in mite
      infested bee pupae, DWV had amplified to extremely high titers with viral genomic
      RNA being clearly visible after separation of total bee RNA in agarose gels.
      Linear regression analysis has shown a positive correlation between the number of
      mites introduced and the levels of viral RNAs. The detection of viral RNAs in the
      nymph and adult mites underline the possible role of varroa in virus
      transmission. However, most groups of virus-free adult mites (9/12) were
      associated with bee pupae heavily infected by viruses, suggesting that the
      elevated viral titers in mite-infested pupae more likely resulted from activated
      viral replication. Based on these observations and our concurrent research
      demonstrating suppressed immune responses in bees infested with mites, we propose
      that parasitization by varroa suppresses the immunity of honey bees, leading to
      activation of persistent, latent viral infection.

PMID- 16109436
TI  - Comparative economic analysis of the impacts of mean cell retention time and
      denitrification on aeration systems.
AB  - Biological nutrient removal is practiced in various modifications of the
      activated sludge process (ASP) throughout the world. This paper compares
      conventional, nitrifying-only and combined nitrifying/denitrifying (NDN)
      processes. The authors performed 113 oxygen transfer efficiency measurements with
      the off-gas method over 20 years. This dataset was analysed and used to perform
      an economic analysis for three example scenarios, one for each layout
      (conventional, nitrifying-only and NDN). Field oxygen transfer efficiency and
      relevant plant operative costs and credits were considered (i.e., aeration cost,
      sludge disposal cost, methane production credit). The conclusion is that NDN
      operations always have lower aeration costs, and generally have the lowest
      combined operating cost. Reduced aeration costs result because of improved
      aeration efficiency at higher mean cell retention times and the use of nitrate as
      an electron acceptor. The improved aeration efficiency overcomes the increased
      oxygen required at higher cell retention time due to cell decay.

PMID- 16109437
TI  - Characterisation of the behaviour of particles in biofilters for pre-treatment of
      drinking water.
AB  - Biofiltration of surface water was examined using granular activated carbon (GAC)
      and expanded clay (EC). Particle removal was 60-90%, measured by flow cytometry,
      which enabled discrimination between total- and autofluorescent particles
      (microalgae) in size ranges of 0.4-1 and 1-15 microm, and measured by on-line
      particle counting. Total particles were removed at a higher degree than
      autofluorescent particles. The biofilters were also challenged with 1 microm
      fluorescent microspheres with hydrophobic and hydrophilic surface characteristics
      and bacteriophages (Salmonella typhimurium 28B). Added microspheres were removed
      at 97-99% (hydrophobic) and 85-89% (hydrophilic) after 5 hydraulic residence
      times (HRT) and microspheres retained in the biofilter media were slowly
      detaching into the filtrate for a long time after the addition. Removal of
      bacteriophages (5 HRT) was considerably lower at 40-59%, and no long-lasting
      detachment was observed. A comparison of experimental data with theoretical
      predictions for removal of particles in clean granular media filters revealed a
      similar or higher removal of particles around 1 microm in size than predicted,
      while bacteriophages were removed at a similar or lesser extent than predicted.
      The results highlight the selectivity and dynamic behaviour of the particle
      removal processes and have implications for operation and microbial risk
      assessment of a treatment train with biofilters as pre-treatment.

PMID- 16109438
TI  - Spatial and temporal trends of contaminants in terrestrial biota from the
      Canadian Arctic.
AB  - Contaminants in the Canadian Arctic have been studied over the last twelve years
      under the guidance of the Northern Contaminants Program. This paper summarizes
      results from that program from 1998 to 2003 with respect to terrestrial animals
      in the Canadian Arctic. The arctic terrestrial environment has few significant
      contaminant issues, particularly when compared with freshwater and marine
      environments. Both current and historical industrial activities in the north may
      have a continuing effect on biota in the immediate area, but effects tend to be
      localized. An investigation of arctic ground squirrels at a site in the Northwest
      Territories that had historically received applications of DDT concluded that DDT
      in arctic ground squirrels livers was the result of contamination and that this
      is an indication of the continuing effect of a local point source of DDT. Arsenic
      concentrations were higher in berries collected from areas around gold mines in
      the Northwest Territories than from control sites, suggesting that gold mining
      may significantly affect arsenic levels in berries in the Yellowknives Dene
      traditional territory. Although moose and caribou from the Canadian Arctic
      generally carry relatively low contaminant burdens, Yukon moose had high renal
      selenium concentrations, and moose and some woodland caribou from the same area
      had high renal cadmium levels, which may put some animals at risk of
      toxicological effects. Low hepatic copper levels in some caribou herds may
      indicate a shortage of copper for metabolic demands, particularly for females.
      Similarities in patterns of temporal fluctuations in renal element concentrations
      for moose and caribou suggest that environmental factors may be a major cause of
      fluctuations in renal concentrations of some elements. Concentrations of
      persistent organochlorines and metals in beaver and muskrat from the Northwest
      Territories, and carnivores from across the Canadian Arctic were very low and
      considered normal for terrestrial wildlife. Two new classes of persistent
      fluorinated contaminants, perfluorooctane sulfonate (PFOS) and perfluoroalkyl
      carboxylates (PFCAs) were found in arctic carnivores and were most abundant in
      arctic fox and least abundant in mink. Although trace element concentrations in
      king and common eider ducks were low and not of toxicological concern, the number
      of nematode parasites in common eiders was positively correlated with total and
      organic mercury concentrations. Future research should focus on cadmium in moose
      and caribou, mercury in caribou, and emerging contaminants, with an effort to
      sample moose and caribou annually where possible to explore the role of naturally
      occurring cycles in apparent temporal trends.

PMID- 16109439
TI  - Persistent organic pollutants and mercury in marine biota of the Canadian Arctic:
      an overview of spatial and temporal trends.
AB  - This review summarizes and synthesizes the significant amount of data which was
      generated on mercury (Hg) and persistent organic pollutants (POPs) in Canadian
      Arctic marine biota since the first Canadian Arctic Contaminants Assessment
      Report (CACAR) was published in 1997. This recent body of work has led to a
      better understanding of the current levels and spatial and temporal trends of
      contaminants in biota, including the marine food species that northern peoples
      traditionally consume. Compared to other circumpolar countries, concentrations of
      many organochlorines (OCs) in Canadian Arctic marine biota are generally lower
      than in the European Arctic and eastern Greenland but are higher than in Alaska,
      whereas Hg concentrations are substantially higher in Canada than elsewhere.
      Spatial coverage of OCs in ringed seals, beluga and seabirds remains a strength
      of the Arctic contaminant data set for Canada. Concentrations of OCs in marine
      mammals and seabirds remain fairly consistent across the Canadian Arctic although
      subtle differences from west to east and south to north are found in the
      proportions of various chemicals. The most significant development since 1997 is
      improvement in the temporal trend data sets, thanks to the use of archived tissue
      samples from the 1970s and 1980s, long-term studies using archeological material,
      as well as the continuation of sampling. These data cover a range of species and
      chemicals and also include retrospective studies on new chemicals such as
      polybrominated diphenyl ethers. There is solid evidence in a few species (beluga,
      polar bear, blue mussels) that Hg at some locations has significantly increased
      from pre-industrial times to the present; however, the temporal trends of Hg over
      the past 20-30 years are inconsistent. Some animal populations exhibited
      significant increases in Hg whereas others did not. Therefore, it is currently
      not possible to determine if anthropogenic Hg is generally increasing in Canadian
      Arctic biota. It is also not yet possible to evaluate whether the recent Hg
      increases observed in some biota may be due solely to increased anthropogenic
      inputs or are in part the product of environmental change, e.g., climate warming.
      Concentrations of most "legacy" OCs (PCBs, DDT, etc.) significantly declined in
      Canadian Arctic biota from the 1970s to the late 1990s, and today are generally
      less than half the levels of the 1970s, particularly in seabirds and ringed
      seals. Chlorobenzenes and endosulfan were among the few OCs to show increases
      during this period while summation operatorHCH remained relatively constant in
      most species. A suite of new-use chemicals previously unreported in Arctic biota
      (e.g., polybrominated diphenyl ethers (PBDEs), short chain chlorinated paraffins
      (SCCPs), polychlorinated naphthalenes (PCNs), perfluoro-octane sulfonic acid
      (PFOS) and perfluorocarboxylic acids (PFCAs)) has recently been found, but there
      is insufficient information to assess species differences, spatial patterns or
      food web dynamics for these compounds. Concentrations of these new chemicals are
      generally lower than legacy OCs, but there is concern because some are rapidly
      increasing in concentration (e.g., PBDEs), while others such as PFOS have unique
      toxicological properties, and some were not expected to be found in the Arctic
      because of their supposedly low potential for long-range transport. Continuing
      temporal monitoring of POPs and Hg in a variety of marine biota must be a
      priority.

PMID- 16109440
TI  - Gene expression profiling of in vitro radiation resistance in cervical carcinoma:
      a feasibility study.
AB  - OBJECTIVE(S): To determine the feasibility of integrating an in vitro chemo
      radiation response assay (IVRRA) with a gene microarray system to investigate the
      molecular patterns of expression that contribute to radiation resistance in
      cervical cancer. METHODS: Viable primary untreated cervical cancer specimens were
      obtained and exposed to gamma irradiation at a dose of 3 Gy in the IVRRA to
      determine in vitro radiation sensitivity. RNA was purified for microarray
      analysis with the Affymetrix Human Genome U95A Array carrying more than 12,000
      gene probes. Gene expression analysis was performed, and specimen transcript
      patterns were correlated with radiation response using an iteration analysis
      model and Pearson's correlation coefficient. RESULTS: A feasibility set of eight
      tumor specimens was studied. Tumors were classified into 4 extreme (ERR), 2
      intermediate (IRR) and 2 low radiation resistance (LRR) categories. An intrinsic
      radiation response gene set of 54 genes transcripts with 100% accuracy for the
      classification of each tumor's radiation response category was identified.
      CONCLUSION(S): Gene sets associated with in vitro radiation response profiles in
      cervical cancer can be generated using the IVRRA and microarray technology. This
      has direct applications to the study of the biological pathways contributing to
      radiation resistance and may lead to the development of alternative treatment
      modalities. The potential of these technologies for cancers in which radiotherapy
      is employed warrants further investigation.

PMID- 16109441
TI  - The impact of converting to liquid-based cervical cytology in a military
      population.
AB  - OBJECTIVE: The liquid-based cytology Pap test was adopted as the exclusive
      collection method for cervical cytology in military treatment facilities within
      the National Capital Area in 2001. We sought to determine the impact of
      converting from conventional to liquid-based cervical cytology. METHODS: A
      retrospective population-based study was performed to analyze the cervical
      cytology results from the National Capital Area for fiscal years 1999, 2000,
      2002, and 2003. Using a computer database, the results of 78,738 conventional and
      76,675 liquid-based cervico-vaginal cytology examinations were reviewed. All
      cytology samples during the study period were collected with the same collection
      device and were processed in a single laboratory. RESULTS: An increase of 116% (P
      < 0.005) in the mean rate of LSIL detection and a 38% (P < 0.005) increase in
      HSIL detection were noted with conversion to liquid-based cytology. A 65% (P <
      0.005) decrease in the mean rate of atypical glandular cell detection was also
      observed. However, a mean increase of 46% (P < 0.005) per year was noted in the
      unsatisfactory rate with conversion to liquid-based cytology. The incidence of
      cervical carcinoma did not change during the study period. CONCLUSIONS:
      Consistent with previous reports, conversion from conventional to liquid-based
      Pap testing in this population resulted in a significant increase in the
      detection rates of both LSIL and HSIL. Contrary to earlier studies, we noted an
      almost 50% increase in the number of unsatisfactory samples after conversion.
      Further studies are warranted to determine the potential etiology of these
      findings to include the role of collection devices.

PMID- 16109442
TI  - Effect of system variables involved in packed column SFC of nevirapine as model
      analyte using response surface methodology: application to retention
      thermodynamics, solute transfer kinetic study and binary diffusion coefficient
      determination.
AB  - A multifactor optimization technique is successfully applied to study the effect
      of simultaneously varying the system variables on feasibility of nevirapine
      analysis by packed column supercritical fluid chromatography (PC-SFC). The
      optimal conditions were determined with the aid of the response surface
      methodology using 3(3) factorial designs. The method is based on methanol
      modified carbon dioxide as the mobile phase at flow rate of 3.0 ml/min with
      elution through a JASCO Finepak SIL-5, [C18 (5-micron, 25 cm x 4.6 mm, i.d.)]
      column using photodiode array detection. The method has been successfully used to
      analyze commercial solid dosage form to assess the chromatographic performance of
      SFC system. The present work briefs the thermodynamic applications of PC-SFC with
      an emphasis on the results of nevirapine. The foremost of such applications is
      the determination of solute diffusion coefficient in supercritical mobile phase
      by Taylor-Aris peak broadening technique.

PMID- 16109443
TI  - Psychic and somatic anxiety differentially predict response to light therapy in
      women with seasonal affective disorder.
AB  - OBJECTIVE: To examine whether psychic and/or somatic anxiety predict
      responsiveness to light therapy in women with winter Seasonal Affective Disorder
      (SAD). DESIGN: Eighty-one women with SAD were administered a standard 10-day
      trial of light therapy administered for one-half hour in the early morning. Using
      a multiple regression model, baseline somatic and psychic anxiety item scores
      were used to predict percentage change scores on the 29-item SIGH-SAD post
      treatment. Baseline scores for weight gain, hypersomnia and the total SIGH-SAD
      were also included as predictor variables. RESULTS: The regression model was
      highly significant (F=4.63, df=5,75; p=.001; model R(2)=.236), with both psychic
      anxiety and somatic anxiety contributing significantly to the model. Consistent
      with prior work using anti-depressant medication in non-seasonal depression,
      psychic anxiety was positively correlated with outcome, while somatic anxiety
      negatively predicted outcome. CONCLUSIONS: In SAD, psychic and somatic anxiety
      scores at baseline appear to be independent and opposite predictors of light
      therapy response. These effects were independent of baseline scores for weight
      gain and hypersomnia, two previously established predictors of response to light.
      These findings may be an important consideration in the design and interpretation
      of light therapy studies of SAD.

PMID- 16109444
TI  - No association found between 158 Val/Met polymorphism of the COMT gene and
      schizophrenia with minor physical anomalies.
AB  - The catechol-O-methyl transferase (COMT) gene has been a promising candidate in
      genetic research on schizophrenia because of its function in dopamine metabolism
      and its location on chromosome 22q11.2, which may be implicated in both
      schizophrenia and velocardiofacial syndrome (VCFS). To explore the possible
      genetic contribution of COMT to the development of schizophrenia, we focused on
      the subgroup of patients with schizophrenia characterized by minor physical
      anomalies as a phenotype and the 158 Val/Met polymorphism as a genotype. Since
      some physical anomalies are found in both schizophrenia and VCFS, schizophrenia
      patients with minor physical anomalies could represent the putative subgroup of
      schizophrenia linked to a disruption in neurodevelopment. Genotyping for the 158
      Val/Met (472 G>A) polymorphism in the COMT gene was done for 239 patients with
      schizophrenia and 248 normal controls. Our analysis did not yield any significant
      between-group differences in terms of either allele or genotype frequency. We
      also could not find any association between the COMT gene and the schizophrenia
      subgroup with minor physical anomalies, although there was a significant
      difference in Waldrop total scores between the patients with schizophrenia and
      the normal controls. Analyses of subgroups based on other clinical variables also
      did not reveal significant differences. Overall, this study does not support the
      hypothesis that the 158 Val/Met polymorphism in the COMT gene is associated with
      schizophrenia in Koreans.

PMID- 16109445
TI  - Human natural killer cells: Molecular mechanisms controlling NK cell activation
      and tumor cell lysis.
AB  - Natural killer cells represent a highly specialized lymphoid population with a
      potent cytolytic activity against virus-infected or tumor cells. Their function
      is regulated by a series of inhibiting or activating signals. The mechanisms by
      which NK cells kill susceptible target cells was thought to be elucidated after
      the discovery of inhibitory receptors specific for MHC-class I molecules: NK
      cells would kill those target cells that lack MHC-class I molecules. However, the
      actual scenario revealed more complex with the discovery of activating receptors
      and their ligands. Thus, in certain pathological conditions, corticosteroid
      treatment or exposure to TGFbeta, NK cells may under-express activating
      receptors. In addition, target cells may lack ligands for activating receptors
      and thus fail to activate NK cells upon cell-to-cell contact. This clearly
      implies that activation of NK cells and of their potent effector mechanism are
      under the control of different checkpoints.

PMID- 16109446
TI  - Maternal dietary choline availability alters the balance of netrin-1 and DCC
      neuronal migration proteins in fetal mouse brain hippocampus.
AB  - Alterations in maternal dietary choline availability during days 12-17 of
      pregnancy led to an increase in the level of immunoreactive netrin-1 and a
      decrease in the level of DCC protein in the developing fetal mouse brain
      hippocampus compared with controls. Changes in the expression of cell migration
      cues during development could account for some of the lifelong consequences of
      maternal dietary choline availability for cognitive and memory processes.

PMID- 16109447
TI  - Sodium butyrate sensitises human pancreatic cancer cells to both the intrinsic
      and the extrinsic apoptotic pathways.
AB  - Pancreatic cancer is characterised by a highly malignant phenotype with a marked
      resistance to conventional therapies and to apoptotic activators. Here, we
      demonstrate that sodium butyrate (NaBt), an inhibitor of histone deacetylases,
      sensitises human pancreatic cancer cell lines to both mitochondria- and Fas
      mediated apoptosis. The analysis of anti-apoptotic and pro-apoptotic members of
      the Bcl-2 family in untreated pancreatic cancer cell lines shows a generalised
      low expression of Bcl-2 and a strong expression of Bcl-xL. NaBt treatment results
      in a marked down-regulation of Bcl-xL expression, mitochondrial membrane
      depolarization, cytochrome c release from mitochondria, activation of caspase-9
      and -3 and apoptosis induction. Furthermore, NaBt sensitises pancreatic cancer
      cells to Fas-mediated apoptosis as well. In fact, the combined treatment with
      NaBt and the agonistic antibody anti-Fas (CH11) is able to induce apoptosis at an
      early time, in which neither NaBt nor CH11 alone induce apoptosis. Down
      regulation of FLIP and activation of caspase-8 allow apoptosis to occur. These
      findings suggest that sodium butyrate could represent a good candidate for the
      development of new therapeutic strategies aimed at improving chemotherapy and
      immunotherapy in pancreatic cancer.

PMID- 16109448
TI  - Early time-locked gamma response and gender specificity.
AB  - The aim was to investigate whether gender is a causative factor in the gamma
      status according to which some individuals respond with time-locked, early gamma
      response, G+, while the others do not show this response, G-. The sample
      consisted of 42 volunteer participants (between 19 and 37 years of age with at
      least 9 years of education). There were 22 females and 20 males. Data were
      collected under the oddball paradigm. Auditory stimulation (10 ms r/f time, 50 ms
      duration, 65 dB SPL) consisted of target (2000 Hz; p = .20) stimuli that occurred
      randomly within a series of standard stimuli (1000 Hz; p = .80). Gamma responses
      were studied in the amplitude frequency characteristics, in the digitally
      filtered event-related potentials (f-ERPs) and in the distributions which were
      obtained using the recently developed time-frequency component analysis (TFCA)
      technique. Participants were classified into G+ and G- groups with a criterion of
      full agreement between the results of an automated gamma detection technique and
      expert opinion. The 2 x 2 x 2 ANOVA on f-ERPs and 2 x 2 x 2 multivariate ANOVA on
      TFCA distributions showed the main effect of gamma status and gender as
      significant, and the interaction between gamma status and gender as
      nonsignificant. Accordingly, individual difference in gamma status is a reliable
      phenomenon, but this does not depend on gender. There are conflicting findings in
      the literature concerning the effect of gender on ERP components (N100, P300).
      The present study showed that if the gamma status is not included in research
      designs, it may produce a confounding effect on ERP parameters.

PMID- 16109449
TI  - Viable count estimates of lag time responses for Salmonella typhimurium M48
      subjected to abrupt osmotic shifts.
AB  - Generally, relative lag times (RLT; lag time divided by generation time) become
      extended as conditions become less favourable for growth. Mellefont et al. (2003,
      2004) [Mellefont, L.A., McMeekin, T.A., Ross, T., 2003. The effect of abrupt
      osmotic shifts on the lag phase duration of foodborne bacteria. Int. J. Food
      Microbiol. 83(3), 281-293; Mellefont, L.A., McMeekin, T.A., Ross, T., 2004. The
      effect of abrupt osmotic shifts on the lag phase duration of physiologically
      distinct populations of Salmonella typhimurium. Int. J. Food Microbiol. 92, 111
      120] reported that abrupt osmotic shifts of Salmonella typhimurium M48 from
      optimal to low aw led to unexpectedly small RLTs at low aw. In this study, RLTs
      resulting from similar osmotic shifts were estimated by viable count (VC) and
      compared to turbidimetric estimates to test the hypothesis that the 'downturn' in
      RLT is an artefact of the turbidimetric technique used. No 'downturn' in RLT was
      observed with VC data and RLTs increased with increasing magnitude of osmotic
      shift. Anomalous turbidimetric estimates of lag time at low aw were confirmed as
      the likely source of the 'downturn' in RLT. The abrupt osmotic shifts resulted in
      a complex pattern of microbial population behaviour. Immediately after transfer
      from optimal aw to low aw, inactivation of a portion of the population occurred
      for all the conditions tested. The degree of inactivation became progressively
      larger with larger shifts in aw. The initial decline in population was followed
      by a period during which no change in numbers occurred, followed by growth that
      appeared, in most cases, to be exponential. At the lowest aws tested (< or
      =0.954), the growth response after the initial decline was at a rate slower than
      that of exponential phase growth. Due to the use of non-selective media
      containing pyruvate (to eliminate oxygen radicals), the observed patterns of
      inactivation, lag and regrowth at most aw conditions are unlikely to result from
      a temporary loss of culturability, but may represent inactivation of a portion of
      the population.

PMID- 16109450
TI  - Use of pulsed-field gel electrophoresis to characterize the genetic diversity and
      clonal persistence of Salmonella senftenberg in mussel processing facilities.
AB  - Salmonella senftenberg was detected in association with persistent contamination
      events in mussel processing facilities between 1998 and 2002 in Spain. A total of
      110 isolates from 8 facilities were subjected to molecular typing by Pulsed-Field
      Gel Electrophoresis (PFGE). Additionally, a selection of epidemiologically
      unrelated isolates of this serovar originating from human, animal, feed and
      environmental sources was included in the study. PFGE analysis proved to be a
      useful tool for studying the persistence and dissemination of S. senftenberg in
      factory environments. Facilities that used brine in their processing lines had
      greater genetic diversity among their S. senftenberg populations, which supports
      the hypothesis that imported salt used for brine preparation could have been the
      origin of the contamination. The XbaI type X19 was the most prevalent among the
      panel, and it was found persisting exclusively in one facility during the 5-year
      study. In general, isolates from mussel processing plants were clearly different
      from those of clinical and environmental sources. However, one of the human
      isolates showed an indistinguishable restriction pattern to an isolate from a
      frozen mussel sample, this could indicate the potential for food-borne
      transmission of this serovar via consumption of contaminated seafood products.
      Isolates in the study were largely sensitive to antimicrobials. Only 9 isolates
      (6 from mussel processing facilities, 1 from soy flour and 2 from meat meal)
      showed antimicrobial resistance.

PMID- 16109451
TI  - Automated genotyping of Saccharomyces cerevisiae using the RiboPrinter.
AB  - This research note addresses the development of an automated molecular typing
      system for yeast. Specifically, our objectives were to generate specific probes
      for genotyping yeast with an automated fingerprinting system. We have adapted the
      RiboPrinter microbial characterization system for use with Saccharomyces
      cerevisiae yeast using alternative probes based on specific multi-copy gene
      families. Manual construction and labeling of probes proved successful in initial
      experiments. Results indicate that this method could be applied to food or
      clinical environments if the appropriate probes are developed.

PMID- 16109452
TI  - Brain-derived neurotrophic factor (Val66Met) genetic polymorphism is associated
      with substance abuse in males.
AB  - Data from animal studies and from genetic scans in humans suggest that brain
      derived neurotrophic factor (BDNF), a member of the neurotrophic factor family,
      may be involved in the mechanisms underlying substance abuse. The present study
      tested the hypothesis that the BDNF-gene Val66Met polymorphism is associated with
      substance abuse. We studied this polymorphism in 103 methamphetamine- and 200
      heroin-dependent cases and 122 normal controls. We also considered the
      association of this polymorphism with age of onset of substance abuse in the
      heroin-dependent cases. Significant differences in BDNF Val66Met genotype
      distribution were found between subjects dependent on methamphetamine (P = 0.046)
      or heroin (P = 0.045) and controls, suggesting that the lower 66Met carrier
      frequency is associated with substance abuse. Furthermore, in the heroin
      dependent group, the Val/Val homozygotes had a later onset of substance abuse
      compared with the Met allele carriers. The results suggest that the BDNF Val66Met
      polymorphism or a nearby locus may be involved in the pathogenesis of substance
      abuse. Our findings support previous genetic scan results showing that BDNF may
      contribute to substance abuse vulnerability.

PMID- 16109453
TI  - Multi-level modelling in health research: a caution and rejoinder on temporally
      mismatched data.
AB  - In a review of the multilevel modelling literature (MLM) we find that data on
      individuals and their social environment contexts (neighbourhoods,
      municipalities) are often drawn from different years/time periods. This temporal
      mismatch has scarcely attracted any attention though it can significantly
      influence modelling results and interpretation. We demonstrate the influence of
      temporal mismatch first by outlining the degree of neighbourhood mobility in
      large metropolitan areas in Britain, Canada and the United States and second with
      a brief MLM example. We conclude that researchers ought to provide more study
      context when such mismatch is unavoidable.

PMID- 16109454
TI  - Homocysteine and folate metabolism in depression.
AB  - Homocysteine is a sensitive marker of folate and vitamin B12 deficiency. Numerous
      studies have confirmed the association between folate deficiency and depression.
      It is not completely understood whether homocysteine is solely a marker for
      folate deficiency or if it may play a more direct role in the expression of mood
      disorders. This review describes the biochemical, neurochemical and clinical
      correlations of folate deficiency and hyperhomocysteinemia in relation to
      depression.

PMID- 16109455
TI  - Increased IgA and IgG serum levels using a novel yam-boxthorn noodle in a BALB/c
      mouse model.
AB  - To determine whether yam-boxthorn noodle, a newly developed functional noodle,
      has immunomodulatory effects in vivo, we measured the changes in visceral organ
      weight, immunoglobulin (Ig) A, IgE, IgG, IgM serum level and IgA level in the
      intestinal lavage fluid of female BALB/c mice after continuously consuming the
      test diet for 5 weeks. We found that body weights and absolute and relative organ
      weights (lung, heart, liver, spleen and kidney) in female BALB/c mice did not
      significantly change compared with those from the control group. The IgA and IgG
      serum levels in the experimental group significantly increased in a dose
      dependent manner when the yam-boxthorn noodle concentration in the AIN 76 diet
      rose from 3% to 30%. However, the IgE and IgM level in the serum and the IgA
      level in the intestinal lavage fluid did not significantly change. These
      experiments demonstrate that the functional noodle, yam-boxthorn noodle, exhibits
      immunomodulatory effects in vivo with increasing serum antibody levels,
      especially in IgA and IgG. These results are valuable for future nutraceutical
      and immuno-pharmacological use.

PMID- 16109456
TI  - Systematic review on analgesics given for pain following tonsillectomy in
      children.
AB  - In this systematic review effectiveness of analgesics for pain after
      tonsillectomy in children was evaluated and trial methodology of the included
      studies explored. Databases were searched for randomised, controlled studies on
      systemic paracetamol, NSAIDs and opioids. Eighty-four studies were evaluated for
      inclusion. Thirty-six studies were included and 48 excluded. Only in two studies
      investigated analgesics were given postoperatively for pain. All other studies
      investigated prophylactic administration of analgesics. Only five studies were
      truly placebo controlled. Trial methodology of the included studies varied
      greatly in respect to analgesics and doses used, duration of follow-up periods,
      methods of pain measurement, rescue analgesics and criteria for administrating
      rescue analgesia used. Sensitivity of studies was often unclear. Only 16 out of
      36 studies were considered to be sensitive. Because of highly variable
      methodology and lack of sensitivity only limited conclusions on clinical efficacy
      of analgesics investigated can be drawn. No analgesic in single prophylactic dose
      provided analgesia for day of operation. Further studies are needed to find the
      optimal analgesic(s) for pain after tonsillectomy in children.

PMID- 16109458
TI  - Interdomain interactions regulate the activation of the heme-regulated eIF 2
      alpha kinase.
AB  - The heme-regulated inhibitor of protein synthesis (HRI) regulates translation
      through the phosphorylation of the alpha-subunit of eukaryotic initiation factor
      2 (eIF 2). While HRI is best known for its activation in response to heme
      deficiency, we recently showed that the binding of NO and CO to the N-terminal
      heme-binding domain (NT-HBD) of HRI activated and suppressed its activity,
      respectively. Here, we examined the effect of hemin, NO, and CO on the
      interaction between the NT-HBD and the catalytic domain of HRI (HRI/Delta HBD).
      Hemin stabilized the interaction of NT-HBD with HRI/Delta HBD, and NO and CO
      disrupted and stabilized this interaction, respectively. Mutant HRI (Delta H
      HRI), lacking amino acids 116-158 from the NT-HBD, was less sensitive to heme
      induced inhibition, and mutant NT-HBD lacking these residues did not bind to
      HRI/Delta HBD. HRI/Delta HBD and Delta H-HRI also activated more readily than HRI
      in response to heme-deficiency. Thus, HRI's activity is regulated through the
      modulation of the interaction between its NT-HBD and catalytic domain.

PMID- 16109459
TI  - Inhibition of the calcium- and voltage-dependent big conductance potassium
      channel ameliorates cisplatin-induced apoptosis in spiral ligament fibrocytes of
      the cochlea.
AB  - The role of calcium- and voltage-dependent big conductance potassium channels in
      regulating apoptosis was investigated in cultured type I spiral ligament
      fibrocytes. Incubation of type I spiral ligament fibrocytes derived from gerbil
      cochlea with cisplatin induced dose- and time-dependent apoptosis as demonstrated
      by annexin V conjugated to fluorescein isothiocyanate/prodidium iodide assays.
      The average voltage activation threshold of whole cell current was sharply
      shifted to -40 mV in the cisplatin-treated cells as compared with a value of 40
      mV in control cells. The average whole-cell current of cisplatin-treated cells
      induced by a depolarization voltage step from -80 to -10 mV was increased
      significantly to 1.2+/-0.4 nA as compared with 0.08+/-0.1 nA in control cells.
      Coincubation with tetraethylammonium and cisplatin retained the whole cell
      current in the normal range (0.12+/-0.2 nA). The increment of cisplatin-induced
      whole-cell current was inhibited (97+/-5%) by a specific calcium- and voltage
      dependent big conductance potassium channel blocker iberiotoxin. Consistent with
      this, co-incubation with tetraethylammonium significantly attenuated cisplatin
      induced apoptosis in type I spiral ligament fibrocytes by more than 50%. We
      conclude that the activation of BK channels is an early event associated with
      cisplatin-induced apoptosis in type I spiral ligament fibrocytes. These findings
      also point to the calcium- and voltage-dependent big conductance potassium
      channels as a potential pharmacological target for manipulating cisplatin
      ototoxicity.

PMID- 16109460
TI  - Imatinib may be useful in the management of patients with glioblastoma.

PMID- 16109461
TI  - Metabolic abnormalities associated with weight loss during chemoirradiation of
      head-and-neck cancer.
AB  - PURPOSE: Weight loss caused by acute mucositis and dysphagia is common during
      concurrent chemoirradiation (chemo-RT) of head-and-neck (HN) cancer. The
      metabolic consequences of weight loss during chemo-RT were investigated. PATIENTS
      AND METHODS: Ninety-six patients with locally advanced HN cancer were treated
      from 1995 to 2001 on protocols that consisted of 1 to 2 cycles of induction
      cisplatin/5-fluorouracil followed by irradiation (70 Gy over 7 weeks) concurrent
      with cisplatin (100 mg/m2 every 3 weeks). Body weights and metabolic evaluations
      were obtained before and during induction chemotherapy and chemo-RT. Greatest
      percent changes in weight and in the laboratory values were calculated for each
      phase of therapy. RESULTS: During induction chemotherapy, significant changes
      were found in BUN, BUN:creatinine ratio, HCO3, Mg, and albumin, but not in
      creatinine, Na, K, or weight. During chemo-RT, significant additional changes
      were observed in all parameters measured, including increases in BUN, creatinine,
      BUN: creatinine ratio, and HCO3 and decreases in Mg, albumin, Na, K, and weight.
      The magnitude of most of these changes was significantly greater during chemo-RT
      than during induction chemotherapy. During chemo-RT, 35% of the patients had more
      than 10% body weight loss and 6 patients had an increase in creatinine of more
      than 100%, including 5 patients with Grade 2 nephrotoxicity, all of whom had
      weight loss 10% or more. Significant correlations were found between weight loss
      and creatinine (p < 0.0001) or BUN (p = 0.0002) rises, but not with
      BUN:creatinine ratio or other metabolic changes. Age, gender, tobacco history,
      hypertension, and diabetes mellitus were not significant predictors of
      nephrotoxicity. CONCLUSIONS: Weight loss during cisplatin-containing chemo-RT was
      found to be associated with reduced kidney function. These findings do not
      establish cause-effect relationships; however, they highlight the importance of
      intensive supportive measures of nutrition and hydration beyond standard
      hydration during cisplatin administration. These intensive measures should be
      enacted before a 10% weight loss is reached.

PMID- 16109462
TI  - American Brachytherapy Society survey regarding practice patterns of
      postoperative irradiation for endometrial cancer: current status of vaginal
      brachytherapy.
AB  - PURPOSE: To survey the current postoperative recommendations for radiotherapy
      (RT) in patients with endometrial cancer, with an emphasis on vaginal
      brachytherapy (VBT). METHODS AND MATERIALS: In August 2003, a 32-item
      questionnaire was mailed to a random sample of 2396 members of the American
      Society for Therapeutic Radiology and Oncology and the American Brachytherapy
      Society. The sample excluded members-in-training, physicists, and non-U.S.
      members. A follow-up mailing was conducted in November 2003. Those who had not
      treated any patient in the previous year for endometrial carcinoma were
      instructed to indicate so at the beginning of the questionnaire and return it
      without responding to any other item. Responses were tabulated to determine the
      relative frequency distribution. RESULTS: of the 2396 surveys sent out, 757 were
      returned, for a response rate of 31.6%. Of those who responded, 551 (72.8%) had
      performed postoperative irradiation for endometrial cancer and were included in
      this study. Of the 551 respondents, 99.8% had delivered external beam RT to some
      endometrial cancer patients. An increasing trend was found toward referrals for
      VBT; 91.5% of those who treated endometrial cancer performed VBT. The vaginal
      target most often irradiated was the upper vagina in 40.7%, upper 4-5 cm in
      54.5%, and the entire vagina in 4.9%; 21.3% placed clips at the vaginal apex for
      applicator verification. The maximal dose to the bladder and rectum was recorded
      in 78.3% and 80.2% of patients, respectively. Of the respondents, 40% did not use
      low-dose-rate (LDR) VBT. The two most common LDR applicators were Delclos
      cylinders (29.7%) and Fletcher colpostats (29.3%). The mean boost dose delivered
      with LDR VBT when prescribed to the surface was 29.9 Gy and when prescribed to
      0.5 cm was 23.8 Gy. When LDR therapy was used without external beam RT, the mean
      dose when prescribed to the surface was 56.8 Gy and when prescribed to 0.5 cm was
      47.9 Gy. In 2002, 69.1% of respondents treated patients with high-dose-rate (HDR)
      VBT. Of the respondents, 90.6% used a single-channel vaginal cylinder, and 83.3%
      of cylinder users followed the curve of the cylinder to optimize dose, 67.9%
      adjusted the applicator position based on localization films, and 47% adjusted
      the applicator to be horizontal. The most common fractionation scheme when using
      HDR VBT as a boost was 5 Gy in three fractions prescribed to 0.5 cm (42.9%). The
      most common fractionation scheme used with HDR without external beam RT was 7 Gy
      in three fractions prescribed to 0.5 cm (41.8%). CONCLUSION: VBT is a common
      recommendation for postoperative adjuvant therapy for endometrial cancer. HDR
      appears to be the most popular approach, with a wide variety of dose
      fractionation schemes reported. Additional study is warranted to help define the
      ideal use of VBT.

PMID- 16109463
TI  - Insertion and fixation of fiducial markers for setup and tracking of lung tumors
      in radiotherapy.
AB  - PURPOSE: Internal 1.5-mm fiducial markers were used in real-time tumor-tracking
      radiotherapy (RT) for lung cancer. The fixation rate of the markers using the
      bronchial insertion technique, reliability of the setup using markers around the
      target volume, dislocation of the markers after real-time tumor-tracking RT, and
      long-term toxicity of marker insertion were investigated. METHODS AND MATERIALS:
      Between July 2000 and April 2004, 154 gold markers were inserted into 57 patients
      with peripheral lung cancer. The distances between the implanted markers in 198
      measurements in 71 set-ups in 11 patients were measured using two sets of
      orthogonal diagnostic X-ray images of the real-time tumor-tracking RT system. The
      distance between the markers and the chest wall was also measured in a transaxial
      CT image on 186 occasions in 48 patients during treatment planning and during
      follow-up. The median treatment time was 6 days (range, 4-14 days). RESULTS: In
      115 (75%) of the 154 inserted markers, the gold marker was detected throughout
      the treatment period. In 122 markers detected at CT planning, 115 (94%) were
      detected until the end of treatment. The variation in the distances between the
      implanted markers was within +/-2 mm in 95% and +/-1 mm in 80% during treatment.
      The variation in the distances between the implanted markers was >2 mm in at
      least one direction in 9% of the setups for which reexamination with a CT scan
      was indicated. The fixation rate in the left upper lobe was lower than in the
      other lobes. A statistically significant relationship was found between a shorter
      distance between the markers and the chest wall and the fixation rate, suggesting
      that the markers in the smaller bronchial lumens fixed better than those in the
      larger lumens. A learning curve among the endoscopists was suggested in the
      fixation rate. The distance between the markers and the chest wall changed
      significantly within a median of 44 days (range, 16-181 days) after treatment.
      CONCLUSION: The fixation of markers into the bronchial tree was useful for the
      setup for peripheral lung cancer and had an accuracy of +/-2 mm during the 1-2
      week treatment period. The relationship between the markers and tumor can change
      significantly after 2 weeks, suggesting that adaptive four-dimensional RT is
      required.

PMID- 16109464
TI  - Economic analysis of a phase III clinical trial evaluating the addition of total
      androgen suppression to radiation versus radiation alone for locally advanced
      prostate cancer (Radiation Therapy Oncology Group protocol 86-10).
AB  - PURPOSE: To evaluate the cost-effectiveness of adding hormone therapy to
      radiation for patients with locally advanced prostate cancer, using a Monte Carlo
      simulation of a Markov Model. METHODS AND MATERIALS: Radiation Therapy Oncology
      Group (RTOG) protocol 86-10 randomized patients to receive radiation therapy (RT)
      alone or RT plus total androgen suppression (RTHormones) 2 months before and
      during RT for the treatment of locally advanced prostate cancer. A Markov model
      was designed with Data Pro (TreeAge Software, Williamstown, MA). The analysis
      took a payer's perspective. Transition probabilities from one state of health
      (i.e., with no disease progression or with hormone-responsive metastatic disease)
      to another were calculated from published rates pertaining to RTOG 86-10.
      Patients remained in one state of health for 1 year. Utility values for each
      health state and treatment were obtained from the literature. Distributions were
      sampled at random from the treatment utilities according to a second-order Monte
      Carlo simulation technique. RESULTS: The mean expected cost for the RT-only
      treatments was 29,240 dollars (range, 29,138-29,403 dollars). The mean
      effectiveness for the RT-only treatment was 5.48 quality-adjusted life years
      (QALYs) (range, 5.47-5.50). The mean expected cost for RTHormones was 31,286
      dollars (range, 31,058-31,555 dollars). The mean effectiveness was 6.43 QALYs
      (range, 6.42-6.44). Incremental cost-effectiveness analysis showed RTHormones to
      be within the range of cost-effectiveness at 2,153 dollars/QALY. Cost
      effectiveness acceptability curve analysis resulted in a >80% probability that
      RTHormones is cost-effective. CONCLUSIONS: Our analysis shows that adding
      hormonal treatment to RT improves health outcomes at a cost that is within the
      acceptable cost-effectiveness range.

PMID- 16109465
TI  - Catch-up growth in Malawian babies, a longitudinal study of normal and low
      birthweight babies born in a malarious endemic area.
AB  - INTRODUCTION: Infant growth has not been studied in developing countries in
      relation to maternal factors related to malaria in pregnancy and maternal
      illiteracy. OBJECTIVE: To describe growth patterns in infants with low and normal
      birthweight and determine maternal risk factors for infant undernutrition.
      METHODS: Babies born in a rural district of southern Malawi were recruited. An
      infant cohort was selected on the basis of low or normal birthweight. Weight and
      length were recorded at birth and at 4-weekly intervals until at 52 weeks after
      birth. Maternal characteristics at first antenatal attendance and delivery were
      obtained. Odds ratios in univariate analysis were adjusted for birthweight.
      Factors included in the multivariate regression included maternal illiteracy,
      season of birth, maternal iron deficiency and number of infant illness episodes.
      RESULTS: Low birthweight infants were shorter and lighter throughout infancy than
      either normal birthweight or international reference values. At 12 months,
      placental or peripheral malaria at delivery (adjusted odds 1.8; 1.0, 3.1), number
      of infant illness episodes (AOR = 2.1; 1.2, 3.6) and maternal illiteracy (AOR =
      2.7; 1.5, 4.9) were independently associated with low weight for age. Maternal
      short stature (AOR = 1.8; 1.1. 3.2), male sex (AOR = 2.4; 1.4, 4.1), number of
      infant illness episodes (AOR = 2.6; 1.5, 4.4), and birth in the rainy season
      (2.1; 1.2, 3.7) were independently associated with stunting. Placental or
      peripheral malaria at delivery (AOR = 2.2; 1.1, 4.4) and number of illness
      episodes (AOR = 2.2; 1.1, 4.5) were independently associated with thinness.
      CONCLUSION: Malaria during pregnancy and maternal illiteracy are important
      maternal characteristics associated with infant undernutrition. Innovative
      health/literacy strategies are required to address malaria control in pregnancy
      in order to reduce the magnitude of its effects on infant undernutrition.

PMID- 16109466
TI  - Stabilizer choice for rapid dissolving high potency itraconazole particles formed
      by evaporative precipitation into aqueous solution.
AB  - The objective of this study was to investigate the influence of stabilizer type
      on the physicochemical properties, including dissolution, of ultra-high potency
      powders containing itraconazole (ITZ) formed by evaporative precipitation into
      aqueous solution (EPAS). ITZ was dissolved in dichloromethane, which was then
      atomized through a heated coil at 80 degrees C into an aqueous solution over
      precise periods of time. Stabilizers were present in either the aqueous, organic
      or both phases. The dispersions were centrifuged and the supernatant was removed.
      Three hydrophilic stabilizers were investigated, including polysorbate 80,
      polyvinyl pyrrolidone and poloxamer 407. Rapid dissolving ultra-high potency of
      ITZ powders was successfully produced. Greater than 80% of ITZ was dissolved in 5
      min compared to only 13% of ITZ bulk powders. The resulting stabilizer-coated
      drug particles had high drug-to-stabilizer ratios greater than 12, corresponding
      to potencies (wt drug/wt drug+wt surfactant) as high as 93%. An increase in
      dissolution rate was correlated with the amount of stabilizer adsorbed and the
      wettability. The combination of polysorbate 80 and poloxamer 407 present in the
      aqueous and organic phases, respectively, was superior in achieving high wetting
      and rapid dissolving ITZ powders. The ability to control the adsorption behavior
      of stabilizers by using synergistic combinations affords the opportunity to
      achieve high dissolution rates with higher potencies compared to previously
      reported values.

PMID- 16109467
TI  - A traditional method of Cinnamomum carolinense preparation eliminates safrole
      from a therapeutic Pohnpean tea.
AB  - Cinnamomum carolinense, locally known as madeu, is a tree endemic to the volcanic
      mountains of the Island of Pohnpei in the Eastern Carolines of the South Pacific.
      The bark is harvested from trees and brewed to make a medicinal tea and hot
      beverage that is regularly consumed. Many species of Cinnamomum contain the known
      hepatocarcinogen safrole, sparking concern regarding habitual consumption of this
      beverage. HPLC-PDA analysis confirmed the presence of the carcinogen in alcoholic
      extracts of Cinnamomum carolinense bark shavings (0.435%, w/w), but safrole was
      not detected in the tea. The limit of detection and limit of quantitation of
      safrole were determined to be 1.25 and 3.75 microg/mL, respectively. The
      traditional preparation method, which boils the bark shavings, degrades the
      safrole.

PMID- 16109468
TI  - Spatio-temporal expression of immediate early genes in the central nervous system
      of SJL/J mice.
AB  - Gene products of immediate early genes (IEGs) interact with specific binding
      sites in promoter regions of inducible and constitutively expressed genes.
      Thereby, they control transcription of down-stream targets, like pro- and anti
      apoptotic genes and matrix-metalloproteinases (MMPs), known to play an important
      role in development, plasticity, response to injury and repair of the central
      nervous system (CNS). A real-time quantitative RT-PCR and immunohistochemical
      investigation was performed to study mRNA expression levels and protein
      distribution patterns of IEGs in cerebrum, cerebellum, and spinal cord of SJL/J
      mice between postnatal weeks 1 and 40. A down-regulation of c-jun, NF-kappaB1,
      Max, Ets-1, and p53 mRNA, and an up-regulation of c-fos mRNA was noticed. Down
      regulations of Ets-1 and p53 were most prominent between week 1 and 3. The
      prominent role in CNS development for c-jun, Ets-1 and Max was supported by
      immunohistochemistry. One-week-old mice were strongly positive for all three
      proteins in cerebral cortex, medulla oblongata, and gray matter of the spinal
      cord. A high staining intensity was detected in the developing granule cell layer
      of the cerebellum for c-jun and Ets-1, and in the Purkinje cell layer of the
      cerebellum for Max. In addition to the general down-regulation of most mRNAs,
      minor up-regulations of all IEG proteins could be detected in restricted parts of
      the CNS indicating regional variations and differential expression and
      translation during development. Apoptosis was demonstrated using
      immunohistochemistry for active caspase-3. The expression patterns of IEGs might
      represent the key to understand the balance of proteolytic activities by MMPs,
      myelination, and the induction of apoptosis during the development of the CNS.

PMID- 16109469
TI  - Advances in axillary surgery for breast cancer--time for a tailored approach.

PMID- 16109470
TI  - Transcriptional profiling of mefloquine-induced disruption of calcium homeostasis
      in neurons in vitro.
AB  - Mefloquine is associated with adverse neurological effects that are mediated via
      unknown mechanisms. Recent in vitro studies have shown that mefloquine disrupts
      neuronal calcium homeostasis via liberation of the endoplasmic reticulum (ER)
      store and induction of calcium influx across the plasma membrane. In the present
      study, global changes in gene expression induced in neurons in response to
      mefloquine-induced disruption of calcium homeostasis and appropriate control
      agents were investigated in vitro using Affymetrix arrays. The mefloquine
      transcriptome was found to be enriched for important regulatory sequences of the
      unfolded protein response and the drug was also found to induce key ER stress
      proteins, albeit in a manner dissimilar to, and at higher equivalent
      concentrations than, known ER-tropic agents like thapsigargin. Mefloquine also
      down-regulated several important functional categories of genes, including
      transcripts encoding G proteins and ion channels. These effects may be related to
      intrusion of extracellular calcium since they were also observed after glutamate,
      but not thapsigargin, hydrogen peroxide, or low-dose mefloquine treatment.
      Mefloquine could be successfully differentiated from other treatments on the
      basis of principle component analysis of its "calcium-relevant" transcriptome.
      These data may aid interpretation of expression of results from future in vivo
      studies.

PMID- 16109471
TI  - Mapping and reconstruction of domoic acid-induced neurodegeneration in the mouse
      brain.
AB  - Domoic acid, a potent neurotoxin and glutamate analog produced by certain species
      of the marine diatom Pseudonitzschia, is responsible for several human and
      wildlife intoxication events. The toxin characteristically damages the
      hippocampus in exposed humans, rodents, and marine mammals. Histochemical studies
      have identified this, and other regions of neurodegeneration, though none have
      sought to map all brain regions affected by domoic acid. In this study, mice
      exposed (i.p.) to 4 mg/kg domoic acid for 72 h exhibited behavioral and
      pathological signs of neurotoxicity. Brains were fixed by intracardial perfusion
      and processed for histochemical analysis. Serial coronal sections (50 microm)
      were stained using the degeneration-sensitive cupric silver staining method of
      DeOlmos. Degenerated axons, terminals, and cell bodies, which stained black, were
      identified and the areas of degeneration were mapped onto Paxinos mouse atlas
      brain plates using Adobe Illustrator CS. The plates were then combined to
      reconstruct a 3-dimensional image of domoic acid-induced neurodegeneration using
      Amira 3.1 software. Affected regions included the olfactory bulb, septal area,
      and limbic system. These findings are consistent with behavioral and pathological
      studies demonstrating the effects of domoic acid on cognitive function and
      neurodegeneration in rodents.

PMID- 16109472
TI  - Modelling ordinal relations with SVMs: An application to objective aesthetic
      evaluation of breast cancer conservative treatment.
AB  - The cosmetic result is an important endpoint for breast cancer conservative
      treatment (BCCT), but the verification of this outcome remains without a
      standard. Objective assessment methods are preferred to overcome the drawbacks of
      subjective evaluation. In this paper a novel algorithm is proposed, based on
      support vector machines, for the classification of ordinal categorical data. This
      classifier is then applied as a new methodology for the objective assessment of
      the aesthetic result of BCCT. Based on the new classifier, a semi-objective score
      for quantification of the aesthetic results of BCCT was developed, allowing the
      discrimination of patients into four classes.

PMID- 16109473
TI  - Application of neural network to humanoid robots-development of co-associative
      memory model.
AB  - We have been studying a system of many harmonic oscillators (neurons) interacting
      via a chaotic force since 2002. Each harmonic oscillator is driven by chaotic
      force whose bifurcation parameter is modulated by the position of the harmonic
      oscillator. Moreover, a system of mutually coupled chaotic neural networks was
      investigated. Different patterns were stored in each network and the associative
      memory problem was discussed in these networks. Each network can retrieve the
      pattern stored in the other network. On the other hand, we have been developing
      new mechanisms and functions for a humanoid robot with the ability to express
      emotions and communicate with humans in a human-like manner. We introduced a
      mental model which consisted of the mental space, the mood, the equations of
      emotion, the robot personality, the need model, the consciousness model and the
      behavior model. This type of mental model was implemented in Emotion Expression
      Humanoid Robot WE-4RII (Waseda Eye No.4 Refined II). In this paper, an
      associative memory model using mutually coupled chaotic neural networks is
      proposed for retrieving optimum memory (recognition) in response to a stimulus.
      We implemented this model in Emotion Expression Humanoid Robot WE-4RII (Waseda
      Eye No.4 Refined II).

PMID- 16109474
TI  - Identification of motifs with insertions and deletions in protein sequences using
      self-organizing neural networks.
AB  - The problem of motif identification in protein sequences has been studied for
      many years in the literature. Current popular algorithms of motif identification
      in protein sequences face two difficulties, high computational cost and the
      possibility of insertions and deletions. In this paper, we provide a new strategy
      that solve the problem more efficiently. We develop a self-organizing neural
      network structure with multiple levels of subnetworks to make an intelligent
      classification of the subsequences obtained from protein sequences. We maintain a
      low computational complexity through the use of this multi-level structure so
      that the classification of each subsequence is performed with respect to a small
      subspace of the whole input space. The new definition of pairwise distance
      between motif patterns provided in this paper can deal with up to two
      insertions/deletions allowed in a motif, while other existing algorithm can only
      deal with one insertion or deletion. We also maintain a high reliability using
      our self-organizing neural network since it will grow as needed to make sure all
      input patterns are considered and are given the same amount of attention.
      Simulation results show that our algorithm significantly outperforms existing
      algorithms in both accuracy and reliability aspects.

PMID- 16109475
TI  - Individualization of pharmacological anemia management using reinforcement
      learning.
AB  - Effective management of anemia due to renal failure poses many challenges to
      physicians. Individual response to treatment varies across patient populations
      and, due to the prolonged character of the therapy, changes over time. In this
      work, a Reinforcement Learning-based approach is proposed as an alternative
      method for individualization of drug administration in the treatment of renal
      anemia. Q-learning, an off-policy approximate dynamic programming method, is
      applied to determine the proper dosing strategy in real time. Simulations compare
      the proposed methodology with the currently used dosing protocol. Presented
      results illustrate the ability of the proposed method to achieve the therapeutic
      goal for individuals with different response characteristics and its potential to
      become an alternative to currently used techniques.

PMID- 16109476
TI  - FGFR4 GLY388 isotype suppresses motility of MDA-MB-231 breast cancer cells by EDG
      2 gene repression.
AB  - Clinical investigations of an FGFR4 germline polymorphism, resulting in
      substitution of glycine by arginine at codon 388 (G388 to R388), have shown a
      correlation between FGFR4 R388 and aggressive disease progression in cancer
      patients. Here, we studied the differential effects of the two FGFR4 isotypes on
      cellular signalling and motility in the MDA-MB-231 human breast cancer cell
      model. cDNA array analysis showed the ability of FGFR4 G388 to suppress
      expression of specific genes involved in invasiveness and motility. Further
      investigations concentrating on cell signalling and motility revealed an
      abrogation of phosphatidylinositol-3-kinase-dependent LPA-induced Akt activation
      and cell migration due to downregulation of the LPA receptor Edg-2 in FGFR4 G388
      expressing MDA-MB-231 cells. Moreover, FGFR4 G388 expression attenuated the
      invasivity of the breast cancer cell line and decreased small Rho GTPase
      activity. We conclude that FGFR4 G388 suppresses cell motility of invasive breast
      cancer cells by altering signalling pathways and the expression of genes that are
      required for metastasis. Therefore, the positive effect of FGFR4 R388 on disease
      progression appears to result from a loss of the tumour suppressor activity
      displayed by FGFR4 G388 rather than the acquisition or enhancement of oncogenic
      potential.

PMID- 16109477
TI  - Protein kinase C and the regulation of the actin cytoskeleton.
AB  - Protein kinase C (PKC) isoforms are central components in intracellular networks
      that regulate a vast number of cellular processes. It has long been known that in
      most cell types, one or more PKC isoforms influences the morphology of the F
      actin cytoskeleton and thereby regulates processes that are affected by
      remodelling of the microfilaments. These include cellular migration and neurite
      outgrowth. This review focuses on the role of classical and novel PKC isoforms in
      migration and neurite outgrowth, and highlights some regulatory steps that may be
      of importance in the regulation by PKC of migration and neurite outgrowth. Many
      studies indicate that integrins are crucial mediators both upstream and
      downstream of PKC in inducing morphological changes. Furthermore, a number of PKC
      substrates, directly associated with the microfilaments, such as MARCKS, GAP43,
      adducin, fascin, ERM proteins and others have been identified. Their potential
      role in PKC effects on the cytoskeleton is discussed.

PMID- 16109478
TI  - The role of peroxisome proliferator-activated receptor-beta/delta in epithelial
      cell growth and differentiation.
AB  - The physiological and pharmacological roles of peroxisome proliferator-activated
      receptor-beta (PPARbeta-also referred to as PPARdelta) are just beginning to
      emerge. It has recently become clear that PPARbeta has a function in epithelial
      tissues, but controversy exists due to inconsistencies in the literature. There
      is strong evidence that ligand activation of PPARbeta can induce terminal
      differentiation of keratinocytes, with a concomitant inhibition of cell
      proliferation. However, the role of PPARbeta in keratinocyte-specific apoptosis
      is less clear. Additionally, the role of PPARbeta in colonic epithelium remains
      unclear due to conflicting evidence suggesting that ligand activation of PPARbeta
      can potentiate, as well as attenuate, intestinal cancer. Recent studies revealed
      that ligand activation of PPARbeta can induce fatty acid catabolism in skeletal
      muscle and is associated with improved insulin sensitivity, attenuated weight
      gain and elevated HDL levels thus demonstrating promising potential for targeting
      PPARbeta for treating obesity, dyslipidemias and type 2 diabetes. Therefore, it
      becomes critical to determine the safety of PPARbeta ligands. This review focuses
      on recent literature describing the role of PPARbeta in epithelial tissues and
      highlights critical discrepancies that need to be resolved for a more
      comprehensive understanding of how this receptor modulates epithelial
      homeostasis.

PMID- 16109479
TI  - Inducible phosphorylation of cortactin is not necessary for cortactin-mediated
      actin polymerisation.
AB  - Cortactin is an SH3 domain-containing protein that contributes to the formation
      of dynamic cortical actin-associated structures, such as lamellipodia and
      membrane ruffles. It was originally identified as a substrate for the protein
      kinase Src; however, the role of tyrosine phosphorylation in the translocation of
      cortactin to the cell periphery and in the subsequent actin polymerisation is
      still unclear. Recently, two serine/threonine kinases, Pak1 and Erk, have been
      implicated in the regulation of cortactin. Therefore, we systematically
      investigated whether phosphorylation on either tyrosine or serine/threonine
      residues is necessary for cortactin function. In COS7 cells over-expressing Vav2
      or treated with EGF, we could not detect tyrosine phosphorylation, although
      cortactin was translocated to cell periphery and induced membrane ruffle
      formation. In addition, the selective MEK inhibitor, PD98059, did not influence
      in vivo the ability of cortactin to bind to and induce membrane ruffles upon Vav2
      over-expression or short-term EGF treatment. Finally, using a constitutively
      active Pak1 mutant, Pak1 T423E, we showed that Pak1 is not capable of
      phosphorylating cortactin either in vitro or in COS7 cells. These results suggest
      that cortactin-mediated actin polymerisation at cell periphery requires only Rac
      activation but neither tyrosine nor serine/threonine phosphorylation.

PMID- 16109480
TI  - Role of CYP3A4 in the regulation of the aryl hydrocarbon receptor by omeprazole
      sulphide.
AB  - Cross-talk between nuclear receptors involved in the control of drug metabolism
      is being increasingly recognised as a source of drug side effects. Omeprazole is
      a well known activator of the aryl hydrocarbon receptor (AhR). We investigated
      the regulation of AhR by omeprazole-sulphide, a degradation metabolite of
      omeprazole, using CYP1A mRNA induction, reporter gene assay, receptor DNA
      binding, ligand binding, nuclear translocation, trypsin digests, and drug
      metabolism analysis in mouse Hepa-1c1c7, human HepG2 cells and primary human
      hepatocytes. Omeprazole-sulphide is a pure antagonist of AhR in Hepa-1c1c7 and
      HepG2 hepatoma cell lines. In Hepa-1c1c7 cells, omeprazole-sulphide is a ligand
      of AhR, inhibits AhR activation to a DNA-binding form, induces a specific pattern
      of AhR trypsin digestion and inhibits AhR nuclear translocation and subsequent
      degradation in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, in
      highly differentiated primary human hepatocytes treated with rifampicin an
      agonist of the pregnane X receptor (PXR), omeprazole-sulphide behaves as an
      agonist of AhR. Inhibition of drug metabolizing enzymes by ketoconazole restores
      the antagonist effect of omeprazole-sulphide. Metabolic LC/MS analysis reveals
      that omeprazole-sulphide (AhR antagonist) is efficiently converted to omeprazole
      (AhR activator) by cytochrome P450 CYP3A4, a target gene of PXR, in primary human
      hepatocytes but not in hepatoma cells in which PXR is not expressed. This report
      provides the first evidence for a cross-talk between PXR/CYP3A4 and AhR. In
      addition, it clearly shows that conclusions drawn from experiments carried out in
      cell lines may lead to erroneous in vivo predictions in man.

PMID- 16109481
TI  - Serine phosphorylation differentially affects RhoA binding to effectors:
      implications to NGF-induced neurite outgrowth.
AB  - Activation of RhoA prevents NGF-induced outgrowth and causes retraction of
      neurites in neuronal cells, including PC12 cells. Despite its inhibitory effect
      on neurite outgrowth, NGF activates GTP loading of and effector binding to RhoA,
      setting up an apparent contradiction. According to the molecular switch
      hypothesis of GTPase function GTP-loading of RhoA should be sufficient to
      activate its effectors uniformly. However, when monitoring NGF-induced binding of
      GTP-RhoA to multiple targets, we noted differential interactions with its
      effectors. We found that NGF elicits a protein kinase A-mediated phosphorylation
      of RhoA on serine(188), which renders it unable to bind to Rho-associated kinase
      (ROK), whereas it retains the ability to interact with other RhoA targets
      including rhotekin, mDia-1 and PKN. We show in vitro and in vivo that
      phosphorylation of serine(188) represents an additional switch, capable of
      directing signals among effector pathways. In the context of PC12 cell
      differentiation, NGF-induced phosphorylation of RhoA on serine(188) prevents it
      from interacting with ROK, which would otherwise block neurite outgrowth.
      Transfection of RhoA(S188A) mutant into PC12 cells prevents NGF-induced neurite
      outgrowth, just like constitutively activated RhoA(14V) does, indicating the
      requirement of this phosphorylation site. Replacement of serine(188) with the
      phosphomimetic glutamate residue in RhoA(V14/S188E) selectively impairs
      interaction with ROK and when transfected into PC12 cells restores NGF-induced
      neurite outgrowth. Therefore, phosphorylation of serine(188) may serve as a novel
      secondary switch of RhoA capable of overriding GTP-binding-elicited effector
      activation to a subset of targets such as ROK, which interact with the C-terminus
      of RhoA.

PMID- 16109482
TI  - Biotin supplementation decreases the expression of the SERCA3 gene (ATP2A3) in
      Jurkat cells, thus, triggering unfolded protein response.
AB  - Protein folding in the endoplasmic reticulum (ER) depends on Ca(2+); uptake of
      Ca(2+) into the ER is mediated by sarco/endoplasmic reticulum Ca(2+)-ATPase 3
      (SERCA3). The 5'-flanking region of the SERCA3 gene (ATP2A3) contains numerous
      binding sites for the transcription factors Sp1 and Sp3. Biotin affects the
      nuclear abundance of Sp1 and Sp3, which may act as transcriptional activators or
      repressors. Here we determined whether biotin affects the expression of the
      SERCA3 gene and, thus, protein folding in human lymphoid cells. Jurkat cells were
      cultured in media containing 0.025 nmol/L biotin (denoted "deficient") or 10
      nmol/L biotin ("supplemented"). The transcriptional activity of the full-length
      human SERCA3 promoter was 50% lower in biotin-supplemented cells compared to
      biotin-deficient cells. Biotin-dependent repressors bind to elements located 731
      1312 bp upstream from the transcription start site in the SERCA3 gene. The
      following suggest that low expression of SERCA3 in biotin-supplemented cells
      impaired folding of secretory proteins in the ER, triggering unfolded protein
      response: (i) sequestration of Ca(2+) in the ER decreased by 14-24% in response
      to biotin supplementation; (ii) secretion of interleukin-2 into the extracellular
      space decreased by 75% in response to biotin supplementation; (iii) the nuclear
      abundance of stress-induced transcription factors increased in response to biotin
      supplementation; and (iv) the abundance of stress-related proteins such ubiquitin
      activating enzyme 1, growth arrest and DNA damage 153 gene, X-box binding protein
      1 and phosphorylated eukaryotic translation initiation factor 2alpha increased in
      response to biotin supplementation. Collectively, this study suggests that
      supplements containing pharmacological doses of biotin may cause cell stress by
      impairing protein folding in the ER.

PMID- 16109483
TI  - Lysine residues in N-terminal and C-terminal regions of human histone H2A are
      targets for biotinylation by biotinidase.
AB  - In eukaryotic cell nuclei, DNA associates with the core histones H2A, H2B, H3 and
      H4 to form nucleosomal core particles. DNA binding to histones is regulated by
      posttranslational modifications of N-terminal tails (e.g., acetylation and
      methylation of histones). These modifications play important roles in the
      epigenetic control of chromatin structure. Recently, evidence that biotinidase
      and holocarboxylase synthetase (HCS) catalyze the covalent binding of biotin to
      histones has been provided. The primary aim of this study was to identify
      biotinylation sites in histone H2A and its variant H2AX. Secondary aims were to
      determine whether acetylation and methylation of histone H2A affect subsequent
      biotinylation and whether biotinidase and HCS localize to the nucleus in human
      cells. Biotinylation sites were identified using synthetic peptides as substrates
      for biotinidase. These studies provided evidence that K9 and K13 in the N
      terminus of human histones H2A and H2AX are targets for biotinylation and that
      K125, K127 and K129 in the C-terminus of histone H2A are targets for
      biotinylation. Biotinylation of lysine residues was decreased by acetylation of
      adjacent lysines but was increased by dimethylation of adjacent arginines. The
      existence of biotinylated histone H2A in vivo was confirmed by using modification
      specific antibodies. Antibodies to biotinidase and HCS localized primarily to the
      nuclear compartment, consistent with a role for these enzymes in regulating
      chromatin structure. Collectively, these studies have identified five novel
      biotinylation sites in human histones; histone H2A is unique among histones in
      that its biotinylation sites include amino acid residues from the C-terminus.

PMID- 16109484
TI  - Absorption of isoflavones in humans: effects of food matrix and processing.
AB  - If soy isoflavones are to be effective in preventing or treating a range of
      diseases, they must be bioavailable, and thus understanding factors which may
      alter their bioavailability needs to be elucidated. However, to date there is
      little information on whether the pharmacokinetic profile following ingestion of
      a defined dose is influenced by the food matrix in which the isoflavone is given
      or by the processing method used. Three different foods (cookies, chocolate bars
      and juice) were prepared, and their isoflavone contents were determined. We
      compared the urinary and serum concentrations of daidzein, genistein and equol
      following the consumption of three different foods, each of which contained 50 mg
      of isoflavones. After the technological processing of the different test foods,
      differences in aglycone levels were observed. The plasma levels of the isoflavone
      precursor daidzein were not altered by food matrix. Urinary daidzein recovery was
      similar for all three foods ingested with total urinary output of 33-34% of
      ingested dose. Peak genistein concentrations were attained in serum earlier
      following consumption of a liquid matrix rather than a solid matrix, although
      there was a lower total urinary recovery of genistein following ingestion of
      juice than that of the two other foods.

PMID- 16109486
TI  - Protein kinase D: activation for Golgi carrier formation.
AB  - Protein kinase D regulates fission at the trans-Golgi network (TGN) of transport
      carriers that deliver cargo to the plasma membrane. PKD is first recruited to the
      TGN through interaction with diacylglycerol and is subsequently activated by
      phosphorylation to promote carrier fission. In a recent study, the relevant
      upstream kinase at the TGN was identified as the novel protein kinase C isoform
      PKCeta, which in turn is activated in response to heterotrimeric G-protein
      activation. These findings indicate the existence of a kinase signaling cascade
      at the TGN that regulates carrier fission and suggest a mechanism by which cargo
      might direct the formation of its transport carriers.

PMID- 16109485
TI  - Riboflavin deficiency causes protein and DNA damage in HepG2 cells, triggering
      arrest in G1 phase of the cell cycle.
AB  - Eukaryotes convert riboflavin to flavin adenine dinucleotide, which serves as a
      coenzyme for glutathione reductase and other enzymes. Glutathione reductase
      mediates the regeneration of reduced glutathione, which plays an important role
      in scavenging free radicals and reactive oxygen species. Here we tested the
      hypothesis that riboflavin deficiency decreases glutathione reductase activity in
      HepG2 liver cells, causing oxidative damage to proteins and DNA, and cell cycle
      arrest. As a secondary goal, we determined whether riboflavin deficiency is
      associated with gene expression patterns indicating cell stress. Cells were
      cultured in riboflavin-deficient and riboflavin-supplemented media for 4 days.
      Activity of glutathione reductase was not detectable in cells cultured in
      riboflavin-deficient medium. Riboflavin deficiency was associated with an
      increase in the abundance of damaged (carbonylated) proteins and with increased
      incidence of DNA strand breaks. Damage to proteins and DNA was paralleled by
      increased abundance of the stress-related transcription factor GADD153.
      Riboflavin-deficient cells arrested in G1 phase of the cell cycle. Moreover,
      oxidative stress caused by riboflavin deficiency was associated with increased
      expression of clusters of genes that play roles in cell stress and apoptosis. For
      example, the abundance of the pro-apoptotic pleiomorphic adenoma gene-like 1 gene
      was 183% greater in riboflavin-deficient cells compared with riboflavin
      sufficient controls. We conclude that riboflavin deficiency is associated with
      oxidative damage to proteins and DNA in liver cells, leading to cell stress and
      G1 phase arrest.

PMID- 16109487
TI  - The evolutionary dynamics of endogenous retroviruses.
AB  - Endogenous retroviruses (ERVs) are vertically transmitted intragenomic elements
      derived from integrated retroviruses. ERVs can proliferate within the genome of
      their host until they either acquire inactivating mutations or are lost by
      recombinational deletion. We present a model that unifies current knowledge of
      ERV biology into a single evolutionary framework. The model predicts the possible
      long-term outcomes of retroviral germline infection and can account for the
      variable patterns of observed ERV genetic diversity. We hope the model will
      provide a useful framework for understanding ERV evolution, enabling the testing
      of evolutionary hypotheses and the estimation of parameters governing ERV
      proliferation.

PMID- 16109488
TI  - The missing link between hydrogenosomes and mitochondria.
AB  - Mitochondria typically respire oxygen and possess a small DNA genome. But among
      various groups of oxygen-shunning eukaryotes, typical mitochondria are often
      lacking, organelles called hydrogenosomes being found instead. Like mitochondria,
      hydrogenosomes are surrounded by a double-membrane, produce ATP and sometimes
      even have cristae. In contrast to mitochondria, hydrogenosomes produce molecular
      hydrogen through fermentations, lack cytochromes and usually lack DNA.
      Hydrogenosomes do not fit into the conceptual mold cast by the classical
      endosymbiont hypothesis about the nature of mitochondria. Accordingly, ideas
      about their evolutionary origins have focussed on the differences between the two
      organelles instead of their commonalities. Are hydrogenosomes fundamentally
      different from mitochondria, the result of a different endosymbiosis? Or are our
      concepts about the mitochondrial archetype simply too narrow? A new report has
      uncovered DNA in the hydrogenosomes of anaerobic ciliates. The sequences show
      that these hydrogenosomes are, without a doubt, mitochondria in the evolutionary
      sense, even though they differ from typical mitochondria in various biochemical
      properties. The new findings are a benchmark for our understanding of
      hydrogenosome origins.

PMID- 16109489
TI  - Olfactory groove meningiomas.
AB  - Meningiomas originating from the olfactory groove account for approximately 10%
      of all intracranial meningiomas. They represent only 2% of all intracranial
      tumors. We present the diagnostic, clinical and pathological features of
      olfactory groove meningiomas and describe our surgical results and complications
      in a series of 25 patients. In 19 patients, surgery was via a bifrontal approach,
      and in the remaining six a pterional approach was used.

PMID- 16109490
TI  - Neurohypophysial peptides: gatekeepers in the amygdala.
AB  - A recent paper by Huber, Veinante and Stoop reports electrophysiological studies
      in slices of the amygdala in which the authors are able to demonstrate a cellular
      and spatial dissociation between the sites of action of oxytocin and vasopressin.
      These studies are important for determining how these brain peptides might gate
      autonomic responses to fear and other emotional stimuli.

PMID- 16109491
TI  - Cognitive modules utilized for narrative comprehension in children: a functional
      magnetic resonance imaging study.
AB  - The ability to comprehend narratives constitutes an important component of human
      development and experience. The neural correlates of auditory narrative
      comprehension in children were investigated in a large-scale functional magnetic
      resonance imaging (fMRI) study involving 313 subjects ages 5-18. Using group
      independent component analysis (ICA), bilateral task-related components were
      found comprising the primary auditory cortex, the mid-superior temporal gyrus,
      the hippocampus, the angular gyrus, and medial aspect of the parietal lobule
      (precuneus/posterior cingulate). In addition, a right-lateralized component was
      found involving the most posterior aspect of the superior temporal gyrus, and a
      left-lateralized component was found comprising the inferior frontal gyrus
      (including Broca's area), the inferior parietal lobule, and the medial temporal
      gyrus. Using a novel data-driven analysis technique, increased task-related
      activity related to age was found in the components comprising the mid-superior
      temporal gyrus (Wernicke's area) and the posterior aspect of the superior
      temporal gyrus, while decreased activity related to age was found in the
      component comprising the angular gyrus. The results are discussed in light of
      recent hypotheses involving the functional segregation of Wernicke's area and the
      specific role of the mid-superior temporal gyrus in speech comprehension.

PMID- 16109492
TI  - Selective response to letter categorization within the left fusiform gyrus.
AB  - Neuroimaging studies that look at reading processes using words, pseudowords,
      nonwords and letters frequently report specific left fusiform gyrus (BA37)
      activations. In the present study, we examined fMRI signal variations within the
      left and right BA37 for paired Latin letters, Korean letters and geometrical
      figures in discrimination and categorization tasks. Data of Pernet et al.
      (Pernet, C., Franceries, X., Basan, S., Cassol, E., Demonet, J.F., Celsis, P.,
      2004. Anatomy and time course of discrimination and categorization processes in
      vision: an fMRI study. NeuroImage 22, 1563-1577) were re-analyzed using a ROI
      methodology that highlights the selective response of the left BA37 to Latin
      letter categorization. First, differences according to stimulus type were
      observed for the categorization task only. Second, we found weaker activation for
      Latin letter categorization than for both geometrical figure and Korean letter
      categorization. Third, only Latin letter categorization elicited as left-sided
      activation, although the direct comparison between regions did not demonstrate a
      significant difference. These data suggest that the left fusiform gyrus sustains
      access to letter representations in memory; and results are discussed with
      reference to the relationship between letter categorization and word recognition
      and to selective vs. specific (i.e. task-independent) neural response.

PMID- 16109493
TI  - Neural correlates of dual-task performance after minimizing task-preparation.
AB  - Previous dual-task neuroimaging studies have not discriminated between brain
      regions involved in preparing to make more than one response from those involved
      in the management and execution of two tasks. To isolate the effects of dual-task
      processing while minimizing effects related to task-preparatory processes, we
      employed a blocked event-related design in which single trials and dual trials
      were randomly and unpredictably intermixed for one block (mixed block) and
      presented in isolation of one another during other blocks (pure blocks). Any
      differences between dual-task and single-task trials within the mixed block would
      be related to dual-task performance while minimizing any effects related to
      preparatory differences between the conditions. For this comparison, we found
      dual-task-related activation throughout inferior prefrontal, temporal,
      extrastriate, and parietal cortices and the basal ganglia. In addition, when
      comparing the single task within the mixed block with the single task presented
      in the pure block of trials, the regions involved in processes important in the
      mixed block yet unrelated to dual-task operations could be specified. In this
      comparison, we report a pattern of activation in right inferior prefrontal and
      superior parietal cortices. Our results argue that a variety of neural regions
      remain active during dual-task performance even after minimizing task-preparatory
      processes, but some regions implicated in dual-task performance in previous
      studies may have been due to task-preparation processes. Furthermore, our results
      suggest that dual-task operations activate the same brain areas as the single
      tasks, but to a greater magnitude than the single tasks. These results are
      discussed in relation to current conceptions of the neural correlates of dual
      task performance.

PMID- 16109494
TI  - Fatal familial insomnia: a model disease in sleep physiopathology.
AB  - Fatal Familial Insomnia (FFI) is characterized by loss of sleep, oneiric stupor
      with autonomic/motor hyperactivity and somato-motor abnormalities (pyramidal
      signs, myoclonus, dysarthria/dysphagia, ataxia). Positon emission tomography
      (PET) disclosed thalamic hypometabolism and milder involvement of the cortex;
      neuropathology severe neuronal loss in the thalamic nuclei variably affecting the
      caudate, gyrus cinguli and fronto-temporal cortices. Genetic analysis disclosed a
      mutation in the PRNP gene and FFI was transmitted to experimental animals, thus
      classifying FFI within the prion diseases. Rare Sporadic Fatal Insomnia (SFI)
      cases occur without PRNP mutation but with features similar to FFI. FFI
      represents a model disease for the study of sleep-wake regulation: (I) the
      profound thalamic hypometabolism/atrophy associated with lack of sleep spindles
      and delta sleep implicate the thalamus in the origin of slow wave sleep (SWS);
      (II) loss of SWS is associated with marked autonomic and motor hyperactivity;
      termed 'agrypnia excitata', this association has been proposed as a useful
      clinical concept representative of thalamo-limbic dysfunction; (III) lack of SWS
      occurs with substantial preservation of stage 1 NREM sleep, implying that the
      latter has mechanisms different from SWS and unaffected by thalamic atrophy;
      accordingly, conflating stage 1 NREM with SWS into NREM sleep is inappropriate.

PMID- 16109495
TI  - Placebo effects in primary insomnia.
AB  - Placebo effects are commonly observed in insomnia clinical trials. With the
      advent of longer-term trials, such effects appear to be remarkably robust and
      durable. In this paper we review the classic factors that are believed to
      contribute to placebo effects and how these factors operate in insomnia
      randomized clinical trials. Beyond this we suggest that the episodic nature of
      insomnia may interact with patient preferences for intermittent dosing in such a
      way as to sustain placebo effects in the long term. An appreciation of the latter
      phenomenon may provide increased power to detect therapeutic outcomes and may be
      used to potentiate clinical gains.

PMID- 16109496
TI  - Dietary high protein and vitamin C mitigate stress due to chelate claw ablation
      in Macrobrachium rosenbergii males.
AB  - Stress due to claw ablation was tested in Macrobrachium rosenbergii males.
      Dietary high protein and vitamin C were supplemented for amelioration of stress.
      We used four different treatments: fed with 25% protein and a normal dose (0.12%)
      of vitamin C (T(1)); 35% protein and a normal dose (0.12%) of vitamin C (T(2));
      25% protein and a high dose (0.24%) of vitamin C (T(3)); and high protein 35% and
      a high dose (0.24%) of vitamin C (T(4)) for 30 days. All test prawns (T(1) to
      T(4)) were subjected to ablation of their second chelate legs after the 15th day
      of the feeding trial. A control treatment was maintained without claw ablation
      and fed with 25% protein. Haemolymph glucose, hepatopancreatic glycogen, muscle
      ascorbate and enzyme activities (glucose 6 phosphatase (G6Pase), fructose-1,6
      bisphosphatase (FBPase), lactate dehydrogenase (LDH), Alanine aminotransferase
      (ALT) in hepatopancreas) were tested at different recovery periods (0, 6, 24 h, 7
      and 14 days). Results indicate a high glucose level immediately after claw
      ablation and a concomitant increase in gluconeogenic enzymes (G6Pase and FBPase).
      However, glycogen reserves were regained in the treatments due to claw ablation
      stress after 24 h. LDH and ALT activity decreased in the hepatopancreas of M.
      rosenbergii up to 24 h after claw ablation. Overall results indicate that claw
      ablation is stressful to M. rosenbergii and high protein and vitamin C diet may
      mitigate stress due to claw ablation.

PMID- 16109497
TI  - DNA typing from skeletal remains following an explosion in a military fort--first
      experience in Ecuador (South-America).
AB  - We present individual body identification efforts, to identify skeletal remains
      and relatives of missing persons of an explosion took place inside one of the
      munitions recesses of the Armoured Brigade of the Galapagos Armoured Cavalry, in
      the city of Riobamba, Ecuador, on Wednesday, November 20, 2002. Nineteen samples
      of bone remains and two tissue samples (a blood stain on a piece of fabric) from
      the zero zone were analysed. DNA extraction was made by Isoamilic Phenol
      Chloroform-Alcohol, and proteinase K. We increased PCR cycles to identify DNA
      from bones to 35 cycles in some cases. An ABI 310 sequencer was used.
      Determination of the fragment size and the allelic designation of the different
      loci was carried out by comparison with the allelic ladders of the PowerPlex 16
      kit and Gene Scan Analysis Software programme. Five possible family groups were
      established and were compared with the profiles found. Classical Bayesian methods
      were used to calculate the Likelihood Ratio and it was possible to identify five
      different genetic profiles in our country. This paper is important because is a
      novel experience for our forensic services, because this was the first time DNA
      had been used as an identification method in disasters, and it was validated by
      Ecuadorian justice like a very effective method.

PMID- 16109498
TI  - Pathological hypersexuality predominantly linked to adjuvant dopamine agonist
      therapy in Parkinson's disease and multiple system atrophy.
AB  - Pathological hypersexuality developed in 13 patients with PD and two patients
      ultimately diagnosed clinically with MSA. Hypersexuality began within 8 months
      after starting dopamine agonist therapy in 14 of 15 cases, including four on
      agonist monotherapy. It resolved in the four cases where the agonist was stopped,
      despite continued levodopa therapy. This was not an isolated behavioral problem
      in most, with additional compulsive or addictive behaviors coinciding in nine
      patients (60%). A systematic literature review of pathological hypersexuality in
      PD revealed similar medication histories; combining these cases with our series,
      26 of 29 patients (90%) were on adjuvant dopamine agonists.

PMID- 16109499
TI  - Post burn muscle wasting and the effects of treatments.
AB  - Severe burns are typically followed by a hypermetabolic response that lasts for
      at least 9-12 months post-injury. The endocrine status is also markedly altered
      with an initial and then sustained increase in proinflammatory 'stress' hormones
      such as cortisol and other glucocorticoids, and catecholamines including
      epinephrine and norepinephrine by the adrenal medulla and cortex. These hormones
      exert catabolic effects leading to muscle wasting, the intensity of which depends
      upon the percentage of total body surface area (TBSA) involved, as well as the
      time elapsed since initial injury. Pharmacological and non-pharmacological
      strategies may be used to reverse the catabolic effect of thermal injury. Non
      pharmacological strategies include early excision and wound closure of burn
      wound, aggressive treatment of sepsis, elevation of the environmental temperature
      to thermal neutrality (31.5+/-0.7 degrees C), high carbohydrate, high protein
      continuous enteral feeding and early institution of resistive exercise programs.
      Pharmacological modulators of the post-burn hypermetabolic response may be
      achieved through the administration of recombinant human growth hormone, low dose
      insulin infusion, use of the synthetic testosterone analogue, oxandrolone and
      beta blockade with propranolol. This paper aims to review the current
      understanding of post-burn muscle proteolysis and the effects of clinical and
      pharmacological strategies currently being studied to reverse it curb these
      debilitating sequelae of severe burns.

PMID- 16109500
TI  - Outcome in patients with an ICD incorporating cardiac resynchronisation therapy:
      differences between primary and secondary prophylaxis.
AB  - BACKGROUND: The incidence of ventricular tachyarrhythmias in ICD patients with
      cardiac resynchronisation therapy (CRT-D) is not well studied. AIM: To analyse
      event free survival in CRT-D patients with a primary or a secondary prophylactic
      ICD indication. METHODS: Prospective, single centre. Eighty-six patients, 44%
      with a primary prophylactic indication. Actuarial event-free rates for mortality
      and arrhythmias were calculated. RESULTS: Baseline clinical characteristics were
      not significantly different between primary and secondary prophylaxis. Primary
      prophylaxis patients were more likely to be in NYHA class III. Over 21 months,
      724 ventricular events with therapy occurred in 36 patients (42%). The actuarial
      event-free rates, at 1 and 3 years, from appropriate ICD therapy were higher
      (P<0.001) for primary (79.0% and 67.8%) than for secondary prophylaxis (45.6% and
      27.0%). Appropriate ICD therapy occurred more in NYHA class II compared to class
      III (P=0.016). Underlying disease (ischemic versus non-ischemic) and functional
      class did not play a role in multivariate analysis. CONCLUSION: Important
      arrhythmic events in patients with heart failure, and CRT-D occur at a very high
      rate when the indication is secondary prophylaxis. Patients with primary
      prophylaxis have an annual event rate of 10%, even though they tend to have a
      worse heart failure class.

PMID- 16109501
TI  - Intrahepatic immunity: a tale of two sites?
AB  - The intrahepatic immune environment is associated with the induction of
      tolerance, yet maintains the capacity to sustain effective responses against
      pathogens. The mechanisms underlying this dichotomy are unclear. Recent data
      indicate that activation of naive CD8(+) T cells occurs within the liver.
      However, in contrast to efficient primary activation observed within the lymph
      nodes, this pathway is relatively ineffective, leading to reduced CD8(+) T-cell
      cytotoxicity and survival. Thus, the outcome of intrahepatic CD8(+) T-cell
      responses might be determined by whether primary activation occurs within the
      tolerogenic environment of the liver, or whether immunity is induced by initial
      antigen encounter within the lymph nodes. These findings support a novel model of
      hepatic-immune interactions, with implications for our understanding of the
      paradoxical nature of liver immunobiology.

PMID- 16109502
TI  - IGF-1, inflammation and stem cells: interactions during muscle regeneration.
AB  - Insulin-like growth factor-I (IGF-1) is an important mediator in numerous
      developmental processes, such as proliferation, differentiation, survival,
      growth, apoptosis and regeneration. Mouse genetics have provided important
      insights into the signalling mechanisms that are necessary for the coordination
      of muscle repair. Recent studies on the role of IGF-1 in the promotion of cell
      recruitment to the injured muscle and the subsequent resolution of the
      inflammatory response have unveiled new perspectives into local repair
      mechanisms.

PMID- 16109503
TI  - Immunology of ischemic vascular disease: plaque to attack.
AB  - Interest and studies focused on the role of immune and inflammatory mechanisms in
      vascular disease have advanced in synchrony with the advances in the
      understanding of innate immune system regulation and the interplay between innate
      and adaptive immunity. Clinical studies have implicated immune and inflammatory
      mechanisms in stroke and acute coronary syndromes. Analyses of genetically
      modified mice and in vitro and in vivo preclinical ischemia models have yielded
      insights into pathobiological mechanisms. Deciphering the role of innate immune
      mechanisms that confer tolerance to ischemia might guide translation of more
      effective therapies. Antigen-targeted and other forms of focused immunomodulation
      that can suppress vessel activation and protect ischemic tissue might ultimately
      find a niche in the prevention and treatment of vascular disease.

PMID- 16109504
TI  - The Plasmodium sporozoite survives RTS,S vaccination.
AB  - The outcome of the Phase IIb trial of RTS,S (a vaccine comprising the
      polypeptides RTS and S) in young Mozambican children consolidated hopes that
      effective vaccination against malaria is a step nearer, and even elicited a
      generous promise of commitment from the Chancellor of the Exchequer of the UK.
      However, it seems that both optimism and generosity should be moderated by the
      failure of this vaccine to induce meaningful protection against infection by
      Plasmodium falciparum and that we should await confirmation of its efficacy in
      diminishing the incidence of severe malaria.

PMID- 16109505
TI  - The effect of pre-storage cooling on 2,3-DPG levels in red cells stored in SAG-M.
AB  - BACKGROUND: The concentration of red cell 2,3-DPG (2,3-diphosphoglycerate)
      rapidly decreases during storage. A favourable effect on red cell 2,3-DPG has
      been demonstrated by rapid cooling of whole blood prior to storage. In our study
      we have investigated how different methods of cooling whole blood immediately
      after donation effect 2,3-DPG levels during storage. STUDY DESIGN AND METHODS:
      Thirty-six whole blood units (in 6 groups) of 450 ml were collected in 63 ml CPD.
      SAG-M was used as preservative solution for red cell concentrates (RCC). The
      units in one group were cooled down at ambient temperature, while units in the
      other groups were cooled down rapidly by different ways immediately after
      bleeding. Samples from the whole blood units were collected at various days
      during storage for 2,3-DPG measurements. RESULTS: The decline in 2,3-DPG during
      the first two weeks of storage was significantly slower in the groups which were
      cooled down rapidly to 17-18 degrees C within 1h after bleeding (all
      p<or=0.0001). CONCLUSION: The rapid fall in 2,3-DPG can be delayed significantly
      by cooling whole blood units rapidly after bleeding. Most of the methods we used
      in our study can easily be implemented in daily routine practise in any blood
      bank.

PMID- 16109506
TI  - Erythropoietin as adjuvant to pre-operative autologous blood donation in total
      hip arthroplasty: new algorithm for use.
AB  - Erythropoietin (rhEPO) has been used in different surgical procedures as a method
      for saving allogeneic blood, with variable efficacy. Forty consecutive patients
      entered the pre-operative autologous blood donation (PABD) program, and during
      donations hemoglobin fell below 115 g/l; they received rhEPO 40,000 U every week
      for three or four weeks (group 1). As control group, 35 consecutive patients who
      entered the PABD program were studied; during donations, hemoglobin levels in
      these patients fell below 115 g/l, but rhEPO was not administered (group 2). Pre
      surgery hemoglobin levels were higher in patients who received rhEPO (134 g/l vs.
      121 g/l; p<0.0002), and an average of 3.47 doses were administered. The number of
      transfused autologous units was 1.6 in group 1 and 2.1 in group 2 (p<0.05), while
      the number of allogeneic units was 0.9 and 0.1, respectively (p<0.0005), so that
      only 5% of patients treated with rhEPO required some allogeneic unit, as compared
      to 40% of those who did not receive rhEPO (p<0.0005). There were no relevant
      adverse effects, but in two patients from group 1, rhEPO treatment had to be
      discontinued because the level of hemoglobin exceeded 150 g/l. The mean duration
      of hospital admission was shorter in the patients who received rhEPO than in
      those who only underwent PABD (8 days vs. 11.8 days; NS). When adequately used,
      rhEPO is an effective and safe alternative to the use of allogeneic blood.

PMID- 16109507
TI  - Leukotriene D4 potentiates fibronectin-induced migration of human lung
      fibroblasts.
AB  - Fibroblasts play an important role in the repair and remodeling processes
      following injury. Leukotriene D4 (LTD4) is a potent mediator in inflammatory
      processes, but the direct effect of cysteinyl leukotrienes on fibroblast
      migration remains unelucidated. In this study, the effect of the LTD4 on normal
      human lung fibroblasts (NHLF) chemotaxis induced by human plasma fibronectin
      (HFn) was investigated using the modified Boyden's chamber technique. LTD4
      potentiated NHLF chemotaxis to HFn in concentration-dependent manner. A specific
      cysteinyl leukotriene receptor type 1 antagonist, pranlukast inhibited this
      effect, indicating that LTD4 affected cell migration via its specific receptor.
      The potentiating effect of LTD4 on fibroblast chemotaxis was completely abolished
      by pertussis toxin (PTX), suggesting that LTD4-induced effect was dependent on
      PTX-sensitive Gi/o signaling. These findings suggest that LTD4 has a potential to
      augment fibroblast chemotaxis, and to contribute to regulation of the wound
      healing and following remodeling in fibrotic processes of the lung.

PMID- 16109508
TI  - Identification of amino acids of Sindbis virus E2 protein involved in targeting
      tumor metastases in vivo.
AB  - Previous studies conducted in our laboratory with Sindbis viral vectors in animal
      models demonstrated excellent in vivo targeting of tumor cells and significant
      reduction of metastatic implant size. To explore the influence of Sindbis strain
      on these factors, we constructed new plasmids from the wild-type Ar-339 Sindbis
      virus strain and compared their sequences. We found differences in the replicase
      and envelope proteins between JT, HRSP, and Ar-339 sequences. We made chimeras
      combining both strains and studied their efficiency in SCID mice bearing tumor
      xenograft using IVIS in vivo imaging techniques. We found that JT envelope
      proteins targeted tumors more efficiently than those of Ar-339, while the Ar-339
      replicase showed increased efficacy in tumor reduction. To determine which
      residues are responsible for tumor targeting, we made mutants of Ar-339 E2
      envelope protein and tested them by IVIS imaging in ES-2 tumor-bearing and tumor
      free mice. The change of only one amino acid from E70 to K70 in Ar-339 E2
      suppressed the ability to target metastatic tumor implants in mice. A K70 and
      V251 double E2 mutant did not reverse the loss of targeting capability. Only the
      mutant with JT E2 and Ar-339 helper targeted tumor, though with less intensity.

PMID- 16109509
TI  - What does it take to bind CAR?
AB  - Recombinant adenoviruses (Ads) have been used as reagents for biological studies
      and therapeutic protocols for the treatment of human patients. The two most
      commonly used Ads, Ad2 and Ad5, infect a broad range of tissues through
      interaction with the coxsackie and adenovirus receptor CAR. Both mutational
      analyses and crystal structure data have established residues in the fiber knob
      and shaft critical for Ad-CAR binding. In this report we review the contributions
      of various residues to Ad-CAR binding, taking into consideration the documented
      cellular tropism of other Ad serotypes.

PMID- 16109510
TI  - Management of vascular anomalies and complication in liver tranplantation.

PMID- 16109511
TI  - Individualized immunosuppression: new strategies from pharmacokinetics,
      pharmacodynamics and pharmacogenomics.
AB  - BACKGROUND: The ultimate goal of transplantation is the donor-specific immune
      tolerance, but at least in the first 15 to 20 years of this century,
      immunosuppressive agents are still the determinant of clinical outcome of
      transplant recipients. Individualizing patient's immunosuppression to optimize
      the balance between therapeutic efficacy and the occurrence of adverse events
      poses a great challenge to physicians. DATA SOURCES: The data in this article
      were taken mostly from MEDLINE (2000-2004), part of which were from the research
      of the authors. RESULTS: Individualized immunosuppression remains a problem
      because of the narrow therapeutic index and wide inter- and intra-patient
      variation of commonly used immunosuppressants. Recent progress in study of
      pharmacokinetics and pharmacodynamics improved the clinical outcome of transplant
      recipients. More importantly, the emergence of pharmacogenomics might provide a
      promising and complementary tool for traditional therapeutic drug monitoring
      (TDM). CONCLUSIONS: Individualizing organ recipient's immunosuppression to
      balance the therapeutic efficacy and the adverse events represents a great
      challenge to transplant clinicians. Pharmacogenomics shows great promise for an
      interesting and hopefully better future.

PMID- 16109512
TI  - Split liver transplantation: a reliable approach to expand donor pool.
AB  - BACKGROUND: Orthotopic liver transplantation as a successful treatment of end
      stage liver disease is hampered by a persistent lack of cadaveric organs. Split
      liver transplantation, which was first successfully performed by Medical School
      of Hannover in 1988, has become a mature surgical technique to expand the donor
      pool. Between 1993 and 1999, split liver transplantation activities have
      increased in Europe from 1.2% to 10.4% in all performed liver transplantations.
      Current data have strongly supported that the survival rate of patients after
      split liver transplantation is not significantly different from that of patients
      after whole-size orthotopic liver transplantation. The most important step of
      donor graft selection is surgeon's observation judged by the experience of
      individual transplant center. The paper aims to provide the guideline of donor
      selection, hepatic graft splitting, and recipient management as well. DATA
      SOURCES: Medical School of Hannover has accumulated plentiful experience of split
      liver transplantation for more than 10 cases ever since 1998. Besides that, we
      also reviewed a variety of literatures from other famous European and American
      centers specialized in this field for many years. RESULTS: According to our
      experience combined with the view points of others, the donor should meet the
      following criteria as well: (1) age less than 50 years; (2) hemodynamics stable;
      (3) ICU less than 5 days; (4) Na less than 170 mmol/L or better if less than 150
      mmol/L. In 1996 and 1997, the Hamburg group and the UCLA group separately
      introduced a breakthrough technique performing split liver transplantation in
      situ. Evidently, the in situ technique has been limited by prolonged time of
      donor organ procurement, coordination with other organ procurement teams, and
      even extra burden on donor hospital. Some groups, therefore, have restored the ex
      situ or bench splitting technique, and fortunately the transplant outcomes of the
      ex situ technique are equivalent to those of the in situ one. Recently some new
      techniques have been introduced to split the liver for two adult patients,
      including the split-cava technique. CONCLUSIONS: It is clear that the most
      important factor for determining the prognosis of the patient is the time of
      receiving liver transplantation, not the type of liver transplantation. We still
      need to pay close attention to the graft to recipient weight ratio (GRWR) and the
      UNOS classification or MELD score before the patient is subjected to split liver
      transplantation.

PMID- 16109513
TI  - Liver transplantation for patients with hepatolithiasis.
AB  - BACKGROUND: Because of its complicated pathological features such as repeated
      cholangitis and multiple operations, hepatolithiasis is difficult to treat and
      often lead to portal hypertension, and liver failure. The aim of this study was
      to investigate the indications of orthotopic liver transplantation (OLT)for
      patients with hepatolithiasis and the improvement of operative techniques and the
      treatment of postoperative complications. METHODS: The data of 4 patients with
      hepatolithiasis who had undergone OLT at our department in recent years were
      reviewed retrospectively. RESULTS: The 4 patients with hepatolithiasis
      complicated with secondary biliary cirrhosis in end-stage liver disease included
      1 woman and 3 men. One patient underwent OLT using veno-venous bypass prior to
      the mobilization of the liver. Two patients were subjected to liver
      transplantation with improved piggyback technique without bypass. One patient
      received OLT without bypass. All patients were operated on successfully and
      recovered uneventfully. Patient 1 had bleeding from the digestive tract on the
      postoperative day 6. Patient 2 had hemorrhage from the digestive tract and a
      leakage of end-to-side intestinal anastomosis on the postoperative day 44.
      Patient 4 was reoperated on because of hemorrhage from the anastomotic stoma of
      the hepatic artery on the postoperative days 8 and 10. In the 4 patients the mean
      operative time was 7.9 hours and blood loss was 910 ml. Postoperative
      pathological analysis revealed biliary liver cirrhosis. Follow-up of all patients
      showed good conditions. CONCLUSIONS: Hepatolithiasis with secondary biliary liver
      cirrhosis in patients with end-stage liver disease is indicated for liver
      transplantation. Veno-venous bypass prior to the mobilization of the liver and
      improved piggyback technique can lower the incidence of intraoperative bleeding,
      the duration of surgery and postoperative complications.

PMID- 16109514
TI  - Nitrite-derived nitric oxide by xanthine oxidoreductase protects the liver
      against ischemia-reperfusion injury.
AB  - BACKGROUND: It was demonstrated that xanthine oxidoreductase (XOR), during
      ischemia, catalyzes the formation of nitric oxide (NO) from nitrite (NO2-) and
      this NO2- -derived NO protects the isolated perfused rat heart against the
      damaging effects of ischemia-reperfusion (I/R) when conventional nitric oxide
      synthase (NOS)-dependent NO production is impaired. Liver is one of the organs
      with the highest XOR concentration. This study was designed to determine whether
      NO2- -derived NO by XOR protects liver against I/R injury in vivo. For its minute
      amounts and active reactivity, NO can not be detected directly in real time in
      vivo by this time. We have to prove the above hypothesis indirectly. METHODS:
      Wistar rats were pretreated with saline, NOS inhibitor L-NAME (10 mg/kg
      intravenously), XOR inhibitor allopurinol (1.5 mg/kg orally), L-NAME +allopurinol
      and NO scavenger carboxy-PTIO (0.6 mg/kg intravenously) respectively (12 animals
      per group). And then, they were subjected to total liver ischemia for 40 minutes
      followed by reperfusion. Blood samples and liver tissues were obtained for
      analysis after 3 hours of reperfusion. Survival was also investigated. RESULTS:
      Allopurinol-treated animals exhibited further increased serum alanine
      aminotransferase(ALT) levels and liver myeloperoxidase(MPO) activities, but
      further decreased liver adenosine triphosphate(ATP) stores after I/R compared to
      saline-treated counterparts (830.5+/-108.3 U/L, 56.5+/-11.0 U/mg protein and
      1.93+/-0.47 mumol/g vs. 505.8+/-184.2 U/L, 41.5+/-10.2 U/mg protein and 3.05+/
      0.55 micromol/g respectively, P < 0.01, P < 0.05 and P < 0.01 respectively). The
      hepatocyte injury was further exacerbated and the overall survival rate was
      significantly decreased after I/R in animals given by allopurinol compared to
      those pretreated by saline (P < 0.05). L-NAME and allopurinol co-treated animals
      exhibited more severe liver injury (P < 0.05 and P<0.01)and a further decreased
      overall survival rate (P < 0.05)compared to L-NAME or allopurinol alone-treated
      counterparts, but they were not different from carboxy-PTIO treated animals (P >
      0.05). CONCLUSION: NO2- -derived NO by XOR in the hypoxic and acidic environment
      induced by hepatic I/R protects the liver against I/R injury in vivo.

PMID- 16109515
TI  - Impact of personality and coping mechanisms on health related quality of life in
      liver transplantation recipients.
AB  - BACKGROUND: With the great development of liver transplantation in China, long
      survival and quality of life after liver transplantation have been matters of
      growing interest. This study was designed to investigate the impact of
      personality and coping skills on the quality of life after liver transplantation.
      METHODS: Fifty-five outpatients who had been followed up after liver
      transplantation at our center were assessed by general quality of life inventory
      (GQOLI-74), a medical coping modes questionnaire (MCMQ), an eysenck personality
      questionnaire (EPQ), and a general condition questionnaire(GCQ). RESULTS: The
      score for material well-being was the lowest(63.22+/-12.67) and for psychological
      well-being the highest(73.43+/-12.60) in 4 dimensions of the GQOLI in post
      transplantation patients. Their main coping method was confrontation (21.40+/
      3.70). The main characteristics of their personality were extraversation (E score
      12.96+/-4.13) and neuroticism (N score 8.20+/-4.90). The total score of the GQOLI
      was positively correlated with confrontation and E score, and it was negatively
      correlated with acceptance and N score. The physical well-being positively
      associated with the E score. The psychological well-being was positively
      correlated with confrontation and L score, and was negatively correlated with
      acceptance, P and N score. Social well-being was positively correlated with
      confrontation and E score, and was negatively correlated with acceptance and N
      score. Material well-being was not correlated with coping methods and
      personality. CONCLUSION: The quality of life in post liver transplantation
      patients is associated with their psychological characteristics.

PMID- 16109516
TI  - Expression of inducible nitric oxide synthase in transplanted rat liver and its
      inhibitory effect.
AB  - BACKGROUND: It is reported that inducible nitric oxide synthase (iNOS) plays an
      important role in rejection. This study was designed to observe the expression of
      iNOS in the transplanted liver tissues and the effect of aminoguanidine(an
      inhibitor of iNOS) and FK506(immunosuppression) on acute rejection after liver
      transplantation. METHODS: All rats were divided into four groups: homogeneous
      (LEW-LEW), acute rejection (BN-LEW), aminoguanidine (BN-LEW), and FK506 (BN-LEW).
      In the last two groups the drugs were used in heterogeneous rats after liver
      transplantation. The expression of iNOS in liver tissues of all groups was
      investigated immunohistochemically. RESULTS: In the acute rejection group, the
      expression of iNOS was extremely positive compared to the other three groups. The
      difference was statistically significant. CONCLUSIONS: During the process of
      acute rejection in rat orthotopic liver transplantation, the enhanced expression
      of iNOS correlates to the severity of rejection. Aminoguanidine and FK506 can
      inhibit the expression of iNOS and palliate acute rejection.

PMID- 16109517
TI  - Construction of human VEGF165 gene eukaryotic expression plasmid and its effect
      on proliferation of vascular endothelial cells.
AB  - BACKGROUND: After organ transplantation, rapid repair of injured vascular
      endothelial cell(VEC) is a key to prevent graft chronic dysfunction besides
      control of immunological rejection. Many studies have confirmed that vascular
      endothelial growth factor 165(VEGF165) could accelerate the repair of VEC injury,
      decrease thrombosis and thrombotic occlusion, and inhibit hyperplasia of the
      intima. This study was designed to construct eukaryotic expression plasmid
      pBudCE4.1/VEGF165, and observe its effect on the proliferation of VEC. METHODS:
      The VEGF165 gene cloned from human heart tissue by RT-PCR was cloned into
      eukaryotic expression plasmid pBudCE4.1. The recombinant expression plasmid
      pBudCE4.1/VEGF165 was identified by restriction enzyme ( Hind III and BamH I)
      digestion analysis, and was sequenced. The pBudCE4.1/VEGF165 was introduced into
      VEC through lipofection transfection. The VEGF165 mRNA expression by Northern
      blot and VEGF165 protein expression was detected by immunocytochemical staining.
      The effect of expression protein on VEC proliferation was detected by flow
      cytometry. RESULTS: The RT-PCR product of the VEGF165 gene was about 576 bp.
      Sequencing analysis revealed that the sequence of the amplified VEGF165 gene was
      identical with that in GenBank. Restrictive enzyme digestion analysis showed that
      recombinant expression plasmid pBudCE4.1/tVEGF165 had been constructed
      successfully. The expression of VEGF165 at mRNA and protein levels in the
      transformed VSMCs had been demonstrated by Northern blot and immunocytochemical
      staining respectively. The expressed product of VEGF165 could notably accelerate
      the proliferation of VECs. CONCLUSIONS: pBudCE4.1/VEGF165 is successfully
      constructed and is expressed in VECs. Expressed VEGF165 can accelerate the VEC
      proliferation. The present study has laid a foundation for potential use of
      VEGF165 gene transfection to prevent and treat vascular stenosis in the
      transplanted organ.

PMID- 16109518
TI  - Risk factors for postoperative complications after liver resection.
AB  - BACKGROUND: Liver resection is still a complicated operation with a high risk of
      postoperative morbidity. This study was undertaken to analyze the risk factors
      for postoperative complications after liver resection. METHODS: From 2001 to
      2004, a total of 146 patients underwent liver resection for malignant or benign
      lesions. Postoperative complications after the resection were classified as
      surgical and medical, their incidences were analyzed retrospectively. The risk
      factors for both surgical and medical complications were analyzed. To increase
      the safety of liver resection, surgical techniques were modified after April
      2003, including control of inflow or outflow and intra-operative test with
      methylene blue. RESULTS: Before April 2003, a series of 58 patients received
      liver resection. Modified surgical techniques were used in liver resections for
      88 patients after April 2003. A total of 36 patients (24.7%) had postoperative
      complications. Surgical and medical complications occurred in 24 and 13 patients
      respectively (One patient had both surgical and medical complications).
      Perioperative blood transfusion was related to a higher risk of surgical
      complications (P < 0.05). Patients with diabetes mellitus were associated with a
      higher risk of medical complications (P < 0.05). Surgical complications and
      postoperative hospitalization were decreased after the use of modified surgical
      techniques (P < 0.05). CONCLUSION: Postoperative surgical complications can be
      decreased by modified surgical techniques, and careful selection of patients for
      liver resection may help to decrease postoperative medical complications also.

PMID- 16109519
TI  - Prevention and management of pleural effusion following hepatectomy in primary
      liver cancer.
AB  - BACKGROUND: Postoperative pleural effusion occurs frequently after hepatectomy.
      The risk factors, prevention and management of postoperative pleural effusion in
      patients with primary liver cancer (PLC) who have undergone hepatectomy and the
      value of the argon beam coagulator (ABC) for the prevention of pleural effusion
      are studied. METHODS: A total of 523 patients with PLC at our institution who had
      had right hepatectomy from July 2000 to June 2004 were studied retrospectively.
      Comparative analysis was made to identify the factors contributing to
      postoperative pleural effusion and the efficacy of various managements. RESULTS:
      Of the 523 patients whose livers were dissociated using argon beam cutting and/or
      coagulation, 20(3.8%) developed pleural effusions; whereas in the other 467
      patients underwent hepatectomy with suture ligation of the diaphragmatic
      secondary wound surface during the same period, 49(10.5%) had pleural effusion (P
      < 0.01). The factors contributing to postoperative pleural effusion included
      subphrenic collection, postoperative hepatic insufficiency with ascites, duration
      of hepatic occlusion and underlying cirrhosis. CONCLUSIONS: Dissociation of the
      liver by argon beam cutting and/or coagulation can save suture ligation of the
      diaphragmatic secondary wound surface and may also prevent postoperative pleural
      effusion. Pleural drainage using an indwelling central-venous-catheter (CVC) in
      the pleural cavity is safe and efficacious.

PMID- 16109520
TI  - Survival factors after resection of small hepatocellular carcinoma.
AB  - BACKGROUND: Early resection of hepatocellular carcinoma is a key measure to
      prolong the survival of patients. This study was designed to summarize our
      experience in surgical resection of small hepatocellular carcinoma (HCC), and to
      analyze the factors influencing the postoperative survival of patients. METHODS:
      The clinicopathologic data of 105 patients with small HCC after resection from
      1986 through 2003 were analyzed; the patients had been followed up for more than
      half a year (median 33 months). Nine clinicopathologic factors, preoperative
      alpha-fetoprotein (AFP) level, liver cirrhosis, Child-Pugh score, tumor size (>2
      cm vs. < or = 2 cm) and number (single vs. multiple), capsule formation, portal
      vein tumor thrombi (PVTT), Edmondson tumor grade and surgical method, were
      analyzed by the log-rank test and the Cox proportional harzards model analysis.
      RESULTS: The cumulative 1-, 3- and 5-year survival rates after the operation were
      86.5%, 70.3% and 55.2%, respectively, and the 1-, 3- and 5-year disease-free
      survival rates were 78%, 58.9% and 45.6%, respectively. One patient died from
      esophagogastric varices hemorrhage in 2 weeks after reoperation. Thirty-six
      patients had intrahepatic recurrence or metastasis postoperatively and 34
      patients died. The Kaplan-Meier method and the Cox proportional harzards model
      analysis indicated that poor Child-Pugh score, tumor more than 2 cm in diameter,
      PVTT and multiple lesions (including satellitic lesions) were adverse factors
      affecting postoperative survival. The Cox proportional harzards model analysis
      indicated that tumor size, PVTT and multiple lesions were the factors influencing
      postoperative disease-free survival. CONCLUSIONS: Limited hepatectomy with a
      margin more than 1 cm is an appropriate surgical approach. Adverse preoperative
      Child-Pugh score and postoperative intrahepatic recurrences are the main factors
      leading to the death of patients with small HCC.

PMID- 16109521
TI  - Effects of combined splenorenal shunt devascularization and devascularization
      only on hemodynamics of the portal venous system in patients with portal
      hypertension.
AB  - BACKGROUND: Shunt and devascularization have totally different effects on
      hemodynamics of the portal venous system, and the actual results of combined
      shunt and devascularization should be determined by more clinical observations.
      This study aimed to evaluate effects on hemodynamics of the portal venous system
      after conventional splenorenal shunt combined with pericardial devascularization
      and pericardial devascularization only. METHODS: In 20 patients who had received
      conventional splenorenal shunt combined with pericardial devascularization(CP)
      and 18 who had received pericardial devascularization and splenectomy(PCDV),
      hemodynamic parameters of the portal venous system were studied by magnetic
      resonance angiography 1 week before and 2 weeks after operation. Free portal
      pressure was detected continuously by a transducer during the operation. RESULTS:
      Compared to the preoperative data, a decreased flow of the portal vein(PVF)
      (563.12+/-206.42 ml/min vs. 1080.63+/-352.85 ml/min, P < 0.05), a decreased
      diameter of the portal vein (PVD) (1.20+/-0.11 cm vs. 1.30+/-0.16 cm, P < 0.01),
      a decreased free portal pressure(FPP) (21.50+/-2.67 mmHg vs. 29.88+/-2.30 mmHg, P
      < 0.01) and an increased flow of the superior mesenteric vein (SMVF) (1105.45+/
      309.03 ml/min vs. 569.13+/-178.46 ml/min, P < 0.05) were found in the CP group
      after operation; a decreased PVD (1.27+/-0.16 cm vs. 1.40+/-0.23 cm, P < 0.05), a
      decreased PVF(684.60+/-165.73 ml/min vs. 1175.64+/-415.09 ml/min, P < 0.05), a
      decreased FPP (24.40+/-3.78 mmHg vs. 28.80+/-3.56 mmHg, P < 0.05) and an
      increased SMVF (697.91+/-121.83 ml/min vs. 521.30+/-115.82 ml/min, P < 0.05) were
      found in the PCDV group. After operation, the PVF of CP group(563.12+/-206.42
      ml/min vs. 684.60+/-165.73 ml/min, P > 0.05) was not decreased significantly
      while FPP (21.50+/-2.67 mmHg vs. 24.40+/-3.78 mmHg, P < 0.01) was decreased
      significantly as compared with that of the PCDV group. CONCLUSIONS: PVF and FPP
      could be decreased by both surgical procedures, but the effect of decreasing FPP
      is much better in the combined procedures than in PCDV. Since there is no
      significant difference in PVF between the two groups, the combined procedures
      could integrate advantages of shunt with those of the devascularization,
      maintaining the normal anatomy structure of the hepatic portal vein, and should
      be one of the best choices for patients with PHT when surgical interventions are
      considered.

PMID- 16109522
TI  - Association of nonalcoholic fatty liver disease with type 2 diabetes: clinical
      features and independent risk factors in diabetic fatty liver patients.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLDeis a common chronic liver
      disease in China, of which diabetic fatty liver (DFLeaccounts for a large
      proportion in clinic. DFL is a disease without specific clinical features and
      lacking of confirmatory laboratory tests, and the etiology of hepatic steatosis
      remains poorly understood. The aim of this paper was to explore the clinical
      characteristics and to determine associated risk factors in type 2 diabetes
      patients with fatty liver. METHODS: A total of 166 patients, 53 in DFL group and
      113 in NDFL (diabetes without fatty liveregroup participated in this study. Serum
      fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), alkaline phosphate (AKP), gamma glutamyl transpeptidase
      (GGT), total cholesterol (TC), triglyceride (TG), high density lipoprotein
      cholesterol (HDL-C)were measured in both groups. And these variables were
      analyzed by using Student's t test and logistic regression model. RESULTS: A
      progressive increase in the level of FBG, ALT, AST, AKP, GGT, TG (P < 0.05) and a
      decrease of HDL-C (P < 0.01) were observed from DFL group to NDFL group. And
      there was no statistical difference in the level of TC between the two groups.
      CONCLUSIONS: Dyslipidemia, dysglycemia and elevation of liver enzyme can be seen
      more frequently in the DFL patients than in the NDFL patients. The successive
      escalation of serum ALT and TG levels and the lower HDL-C level are the
      independent risk factors of DFL.

PMID- 16109523
TI  - Effects of HBV gene variations on disease development and antiviral therapy for
      patients with chronic hepatitis B.
AB  - BACKGROUND: Viral variation may change pathogenicity, escape immunity, lead to
      persistence infection, and cause drug resistance against antiviral therapy. This
      study was undertaken to investigate the effects of HBV gene variation on the
      progression of disease and on the efficacy of antiviral therapy for patients with
      chronic hepatitis B(CHB). METHODS: Hepatitis B virus(HBV) gene mutational sites
      were detected using gene chip in selected hepatitis B patients. RESULTS: In the
      patients HBeAg did not show serologic conversion or HBeAg(-)/anti-HBe(+), but
      their HBV DNA remained positive 24 weeks after alpha-interferon therapy, which
      was associated with mutations of nt1896, nt1814, nt1762 and nt1764. In the
      patients, that HBV DNA levels decreased or were undetectable, but rebounded later
      after antiviral therapy by lamivudine was associated with mutations of aa528 and
      (or) aa552 (i.e. YMDD mutation),which resulted in lamivudine-resistance. YMDD
      mutation was prone to occur 52 weeks after lamivudine therapy in some chronic
      hepatitis B patients (26.4%). Nt1896 mutation was common in most chronic
      hepatitis B patients (68.5%). Chronic severe hepatitis, cirrhosis, and primary
      liver carcinoma were related to the mutations of nt1896, nt1762 and nt1764.
      CONCLUSIONS: HBV gene mutations could aggravate patient's condition and affect
      the efficacy of antiviral therapy. The regular detection of HBV gene mutation is
      helpful for identification of disease prognosis and adjustment of therapeutic
      strategy.

PMID- 16109524
TI  - Preparation and analysis of cSNP chip on hepatocellular carcinoma-related genes.
AB  - BACKGROUND: The understanding of cSNPs of cancer-related genes harboring in high
      frequency loss regions of tumor chromosomes can advance the disclosure of genetic
      and variant mechanisms of tumorigenesis, and the investigation of cancer
      susceptibility. In preparing a gene chip for detecting polymorphisms on coding
      region of genes in hepatocellular carcinoma tissues, some cSNPs are of interest
      for their potential links with phenotype. METHODS: The genes harboring in loss
      regions with high frequency of hepatocellular carcinoma (HCC) were selected, the
      related information of cSNP sequences was obtained from the SNP database (dbSNP)
      of the National Center for Biotechnology Information (NCBI). Then appropriate
      primers and oligonucleotide probes were designed according to the SNP sites, and
      a gene chip for the detection of SNPs was constructed. The chip included 48 cSNPs
      of 25 hepatocellular carcinoma-related genes. The PCR products labeled by Dig
      dUTP were hybridized with the cSNP chip. RESULTS: The sensitivity, influence by
      probe concentration, and reiteration of the chip were detected, with a high
      sensitivity of 6X10(-3) ng/mul. The signal of hybridization was reduced with a
      lower concentration of probe. Seven polymorphisms of caspase 9 (rs2308941)C-->T
      and DOK2(rs2242241) T-->G, 6 of polymorphisms of EGFL3 (rs947345)A -->G, caspase
      9 ( rs2308938) C-->G and PHGDH(rs1801955)T-->A, 5 of polymorphisms of
      E2F2(rs3218170) G-->A,4 of polymorphisms of MUTYH(rs1140507)T-->C and
      BNIP3L(rs1055806)G-->T, and 1 of polymorphism of TNFRSF1B (rs1061622)T-->G were
      detected by the chip in the tissues of 10 HCC. Samples of caspase 9 (rs2308941G)
      and (rs2308941A) were verified by PCR-SSCP and sequencing. CONCLUSION: The cSNP
      chip of hepatocellular carcinoma-related genes can accelerate the discovery of
      polymorphic markers on hepatocellular carcinoma.

PMID- 16109525
TI  - Effect of IFNalpha-2a on Fas expression and apoptosis rate of peripheral blood
      cytotoxic T cells in patients with hepatitis B.
AB  - BACKGROUND: Interferon(IFN) with antiviral and immunomodulatory activities is one
      of the most important therapeutic agents for the treatment of chronic hepatitis.
      The apoptotic effect of IFN is influenced by cell type and the types of IFN,
      which suppresses proliferation and induces apoptosis in some cell types while
      inhibiting apoptosis in others. The aim of this study was to explore the effect
      of IFNalpha-2a on Fas expression and the apoptosis rate of peripheral blood
      cytotoxic T cells(CTLs) in patients with hepatitis B. METHODS: Peripheral blood
      mononuclear cells were isolated from 26 patients with hepatitis B including 16
      patients with chronic hepatitis B and 10 patients with chronic severe hepatitis
      B. Fas expression and apoptosis rate of CTLs were analyzed with flow cytometry
      before and after IFNalpha-2a treatment. RESULTS: Before IFNalpha-2a treatment,
      Fas expression and apoptosis rate of CTLs from patients with chronic hepatitis B
      were significantly higher than those from patients with chronic severe hepatitis
      B and healthy controls respectively. No significant difference was observed
      between Fas expression and apoptosis rate of CTLs from patients with chronic
      severe hepatitis B and healthy controls. After IFNalpha-2a treatment, Fas
      expression and apoptosis rate of CTLs from different groups were compared with
      those before IFNalpha-2a treatment, showing no significant difference despite
      alternation of different degree. CONCLUSIONS: Activation induced cell death
      (AICD) exists in peripheral blood CTLs from patients with hepatitis B. No effect
      of IFNalpha-2a exerts on Fas expression and apoptosis rate of Fas in patients
      with hepatitis B.

PMID- 16109526
TI  - Evaluation of diffusion weighted imaging of magnetic resonance imaging in small
      focal hepatic lesions: a quantitative study in 56 cases.
AB  - BACKGROUND: Diffusion-weighted imaging (DWI) as a new technique of magnetic
      resonance imaging (MRI) is used to detect focal hepatic lesions. This study was
      designed to evaluate the significance of DWI to differentiate focal hepatic
      lesions less than 3 cm in diameter by the quantitation of apparent diffusion
      coefficient (ADC) values. METHODS: DWI using 1.5T MRI scanner unit was performed
      with a spin-echo single-shot echo planar imaging (EPI) in 56 cases of small focal
      hepatic lesions, including hepatocellular carcinoma (11), hepatic metastatic
      tumor (15), hepatic cavernous hemangioma (14), and hepatic cyst (16). The ADC
      values of these lesions were calculated respectively. The ratios of the ADC
      values of lesion/liver in hepatocellular carcinomas and hepatic metastatic tumors
      were also estimated. RESULTS: The mean ADC values (mm2/s) were (0.93+/-0.06) x
      10(-3) in hepatocellular carcinomas, (1.09+/-0.18) x 10(-3) in hepatic metastatic
      tumors, (1.95+/-0.38) x 10(-3) in hepatic cavernous hemangiomas, and (3.18+/
      0.33) x 10(-3) in hepatic cysts. The ratios of ADC values of lesion/liver were
      0.90+/-0.06 and 1.15+/-0.14 in hepatocellular carcinoma and hepatic metastatic
      tumors respectively, which were significantly different (P < 0.05). CONCLUSION:
      The measurement of ADC values and the ratios of ADC values of lesion/liver are
      helpful in MR diagnosis and differentiation of focal hepatic lesions.

PMID- 16109527
TI  - Lipopolysaccharide decreasing albumin expression in rat hepatocytes.
AB  - BACKGROUND: The relations of the severity of hypoalbuminemia to morbidity and
      mortality of patients with critical illness illustrate the need for better
      understanding of molecular mechanism of hypoalbuminemia. This study was
      undertaken to investigate the response of albumin synthesis to lipopolysaccharide
      (LPS)in rat hepatocytes in vitro in early acute phase of sepsis. METHODS:
      Hepatocytes were cultured at an initial cell density of 1.5 x 10(6) cells/well in
      3 ml culture medium. There were two groups of samples which received either
      normal saline or 1 microg/L LPS randomly. Albumin mRNA in hepatocytes was
      assessed by reverse transcription-polymerase chain reaction (RT-PCR)and albumin
      level in the supernatant was measured by ELISA at 0, 2, 8, 12, 24 hours after
      exposure. Meanwhile, the albumin precursor was evaluated at the same time points
      by flow cytometry. RESULTS: The quantitative changes of mRNA,albumin precursor
      and its protein were analogous. All of them tended to decline at 12 hours post
      treatment and did not decrease significantly until 24 hours after LPS exposure.
      Meanwhile, albumin mRNA decreased about 30% and the levels of albumin precursor
      and albumin reduced approximately 50%. CONCLUSIONS: LPS can inhibit albumin
      synthesis in rat hepatocytes by prevention of albumin transcription. Moreover,
      the response of hepatic albumin synthesis to LPS changes with the stage of sepsis
      process. The results show that albumin metabolism in sepsis is a complicated
      process and further studies are required to understand the molecular mechanism of
      LPS-induced hypoalbuminemia in sepsis.

PMID- 16109528
TI  - Effects of deep low temperature on secondary branches enclosed in Glisson's
      system of pig hepatic lobes.
AB  - BACKGROUND: Hepatic cryosurgery, a safe and effective approach for an
      unresectable hepatoma, has been extensively applied in clinical setting. But
      whether direct deep freezing to the tumor involving special location, i.e.,
      Glisson's system of certain hepatic lobe could cause the impairment of the duct
      system or post impairment effect remains a mystery. Consequently, the aim of the
      study was to investigate the effect of freezing on the secondary branches
      enclosed in the Glisson's system of certain hepatic lobes. METHODS: Twenty pigs
      were divided into 2 groups randomly. The treated group: the area of secondary
      branches of the Glisson's system in the left lateral lobe was frozen by a
      cryoprobe at deep low temperature for 3 minutes, with the blockage of blood flow
      from the porta hepatis. The control group: only the blockage of the porta hepatis
      was performed for 3 minutes. Serologic examinations, color Doppler examination
      and pathological observation were used for evaluation of this procedure
      postoperatively. RESULTS: The frozen hepatic parenchyma, the wall of the frozen
      secondary bile duct and portal vein showed necrosis. However, the frozen hepatic
      artery ramification did not show any obvious changes postoperatively. Eight weeks
      after cryosurgery, the lumen of the hepatic artery and portal vein maintained
      unobstructed. Meanwhile, atrophy and fibroplasia occurred in the related hepatic
      lobe. All the animals recovered well. CONCLUSIONS: Animals could tolerate the
      direct deep-freezing of the area of secondary branches enclosed in the Glisson' s
      system. The therapeutic effect could be attained by the necrosis of the frozen
      hepatic parenchyma.

PMID- 16109529
TI  - Effects of ethanol on liver sinusoidal endothelial cells-fenestrae of rats.
AB  - BACKGROUND: Important advances have been made in research into the mechanism of
      alcoholic liver disease (ALD) over the past few years, but the role of liver
      sinusoidal endothelial cell (LSEC) in ALD has not been elucidated adequately.
      This study was undertaken to investigate the effect of ethanol on fenestrae of
      LSECs in rats. METHODS: A rat model of alcoholic liver disease was established by
      means of direct intragastric instillation of ethanol. Fifty-five rats of
      experimental (35 rats) and control (20) groups were sacrificed at the end of 4,
      8, 12 weeks respectively, and also at the end of 12-week abstinence. After heart
      perfusion, the liver tissue was fixed and stained with hematoxylin and eosin for
      observation of serial changes of LSEC-fenestrae under a transmission electron
      microscope. RESULTS: Normal LESC was flat with a nucleus and organelles arranged
      regularly. The distal cytoplasm displayed as a lamina with many fenestrae,
      lacking the basement membrane(BM) underneath the endothelium. At the end of 4
      week alcohol feeding, the number of fenestrae decreased at the distal cytoplasm
      in some LSECs, without the formation of the BM underneath the endothelium. At the
      end of 8 weeks, the number of fenestrae decreased significantly or even
      disappeared. The BM began to develop incompletely underneath the endothelium,
      while the active fibroblast appeared. At the end of 12 weeks, the number of
      fenestrae decreased more significantly and the complete BM could even be seen.
      But the changes were mostly limited in the single or adjoining sinus, and
      fibrosis was scarcely formed. At the end of 12-week abstinence, defenestration
      and formation of the endothelial BM lightened significantly. CONCLUSIONS:
      Defenestration and formation of the BM in LSECs develop gradually with the
      chronic stimulation of ethanol. Hepatic sinusoidal capillarization and fibrosis
      will be seen if their state is more serious. These early changes, i.e., limited
      and regional defenestration and capillarization may be the basis of alcoholic
      peri-fibrosis. This kind of hepatic fibrosis is reversible after removal of
      etiological factors.

PMID- 16109530
TI  - Magnetic resonance imaging of hepatocellular carcinoma induced by
      diethylnitrosamine in Sprague-Dawley rats.
AB  - BACKGROUND: Diethylnitrosamine (DENA) is able to induce various benign and
      malignant liver lesions in rats with a high success rate and a low mortality
      rate. It provides a more appropriate model that better simulates the various
      lesions occurring in humans than the usual model of tumor implantations. The aim
      of the present study was to evaluate MRI liver examination in Sprague-Dawley (SD)
      rats as a routine method to detect hepatocellular carcinoma (HCC) nodules induced
      by DENA and to follow up their growth. METHODS: Hepatic carcinogenesis was
      induced in 80 male SD rats using oral DENA solution. All animals were imaged for
      liver tumor detection with a 1.5 Tesla magnet (Siemens Sonata, Erlangen, Germany)
      using correspondence scan parameters and a radio-frequency knee coil. Macroscopic
      examinations were performed along the axial MRI sections to evaluate magnetic
      resonance imaging (MRI) findings, and histopathological assessment was also
      performed. RESULTS: No false negative results were obtained on MR images. Hepatic
      tumors in 72 rats were confirmed macroscopically and 68 rats were detected by MRI
      till the 20th week. The smallest and the largest nodules detected by MRI were 2
      mm and 37 mm in diameter respectively. The agreement rate of MRI with macroscopic
      observation was 39.1% and 97.4% respectively for 2 mm to 5 mm and more than 5 mm
      nodules. CONCLUSIONS: The hepatic tumor induced by DENA provides a more
      representative range of tumors for imaging diagnosis and interventional
      treatment. MRI is the best approach for scrutinizing pathological changes of rat
      livers in the period of observation.

PMID- 16109531
TI  - Inhibitory effect of EGFR antisense oligodeoxynucleotide on human hepatoma cell
      line.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancer
      related causes of death worldwide. The epidermal growth factor receptor (EGFR) is
      highly expressed in many human tumors and provides a new target for anticancer
      drug development. The aim of the present study was to explore the effect of EGFR
      antisense oligodeoxynucleotide on human HCC. METHODS: SMMC-7721 cells in culture
      were treated with 10 mumol/L antisense-odn for 24, 48, 72 hours respectively and
      MTT assay was adopted to determine the proliferation of tumor cells in vitro.
      About 2 x 10(6) SMMC-7721 cells with or without pretreatment(30 micromol/L
      oligodeoxynucleotide) were inoculated into subcutaneous flap of 21 nude mice, of
      which 7 were treated with EGFR antisense-odn, 7 with scrambled
      oligodeoxynucleotide (scrambled-odn), and 7 not treated in vivo. RESULTS: In
      vitro, after 24, 48, 72 hours the inhibitory rate of proliferation of SMMC-7721
      cells treated with EGFR antisense-odn was 8%, 32%, and 34% respectively. In vivo
      after 8 weeks, no palpable tumor was found in 1/7 mice receiving cells pretreated
      with antisense-odn, whereas 7/7 untreated mice and 6/7 mice treated with
      scrambled-odn developed palpable tumors. Tumor growth in antisense-odn treated
      mice was significantly inhibited in comparison with that of those untreated (P <
      0.01) or treated with scrambled-odn (P < 0.05). CONCLUSIONS: Antisense
      oligodeoxynucleotide acts as a specific growth inhibitor on SMMC-7721 in a
      sequence specific and time-dependent manner. EGFR antisense-odn can significantly
      inhibit the proliferation of human hepatoma cell in vitro as well as in vivo,
      indicating that EGFR may play an important role in the development of hepatoma
      and will be a new target for its treatment.

PMID- 16109532
TI  - Sedation and safety of propofol for therapeutic endoscopic retrograde
      cholangiopancreatography.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the most
      complex gastrointestinal procedure, which needs patients' cooperation. The aim of
      this study was to observe the quality and safety of sedation with propofol in
      patients undergoing therapeutic ERCP. METHODS: Seventy patients who had undergone
      therapeutic ERCP were randomly divided into two groups. One group,given
      intravenously propofol,and the other sedated with routine method,served as the
      control. Blood pressure,heart rate, oxygen saturation were monitored and
      cardiorespiratory event was observed. Patient cooperation, performance, recovery
      time and amnesia served as variables postoperation. RESULTS: Blood pressure
      elevated in four patients in the propofol group, less than in the control group
      (P < 0.01). Seven patients showed decreased blood pressure after administration
      of propofol, but none in the control group (P < 0.01). Twelve patients in the
      control group showed mild or significant resistance, but none in the propofol
      group (P < 0.01). The time for performance in the propofol group (P < 0.05) was
      shorter than in the control group. Patient recovery was quicker in the propofol
      group than in the control group (P < 0.01). The degree of amnesia better in the
      propofol group than in the control group (P < 0.01). The degree of amnesia was
      also better in the propofol group than in the control group (P<0.01).
      CONCLUSIONS: Propofol proves to be an excellent sedative for therapeutic ERCP.
      Being effective and safe, it shows a shorter ERCP duration but quick recovery and
      better amnesia. It is better than other routine sedatives.

PMID- 16109533
TI  - Pathogenesis and treatment to postoperative bile leakage: report of 38 cases.
AB  - BACKGROUND: Bile leakage remains a serious complication after biliary surgery.
      The aim of this study was to assess the etiology, diagnosis and treatment of
      postoperative biliary leakage. METHODS: Thirty-eight patients with biliary
      leakage we treated in recent 8 years were analyzed retrospectively. Among them, 8
      patients had bilioenterostomy leakage, 7 accessory bile duct leakage, 7 cholecyst
      bed leakage, 6 leakage after removal of T-tube, 5 leakage after laparoscopic
      cholecystectomy, 3 leakage around T-tube, and 2 leakage caused by choledochal
      damage. Drainage was performed in 17 patients, reoperation in 13, drainage plus
      percutaneous transhepatic cholangio drainage (PTCD), endoscopic retrograde
      cholangiography (ERCP), endoscopic nasobiliary drainage (ENBD) and endostenting
      in 5, and drainage plus growth hormone in 3. RESULTS: In this series, 37 patients
      were cured, and 1 died of multiple organ dysfunction syndrome (MODS). These
      patients were hospitalized for 2 weeks to 8 weeks. The drainage group was
      hospitalized shorter than the undrainage group. CONCLUSIONS: A piece of white
      gauze can be used to touch surgical area in detecting biliary leakage
      intraoperatively. Mucous to mucous suture of the bile duct and appropriate time
      for removal of T-tube are recommended to prevent biliary leakage. Reoperation is
      essential to acute peritonitis. Drainage can be used if leakage don't diffuse or
      it occurs after pulling out T-tube. Drainage plus ERCP, ENBD, PTCD and drainage
      are effective.

PMID- 16109534
TI  - Effects of recombinant human growth hormone on intestinal translocation of
      bacteria and endotoxin in rats with obstructive jaundice.
AB  - BACKGROUND: Extrahepatic biliary obstruction promotes intestinal translocation of
      bacteria and endotoxin and this process is an important cause of morbidity and
      mortality in patients with jaundice. This study was undertaken to investigate the
      effect and mechanism of recombinant human growth hormone(rhGH) and to alleviate
      intestinal translocation of bacteria and endotoxin in murine obstructive
      jaundice. METHODS: A group of 42 Wistar rats were divided into 3 groups:sham
      operation(SO), bile duct ligation (BDL), and BDL and rhGH treatment(rhGH). By the
      end of the experiment, on day 7, the animals were killed, and their liver
      function and serum endotoxin were measured, bacterial cultures of the liver,
      kidney and mesenchymal lymph were made. Terminal ileum mucosa was observed under
      an electron microscope. RESULTS: Liver function was improved more significantly
      in the rhGH group than in the BDL group. The value of endotoxin in the rhGH group
      was 0.38+/-0.03 EU/ml, significantly lower than that in the BDL group(0.65+/-0.04
      EU/ml, P < 0.01), and similar to that in the SO group (0.30+/-0.02 EU/ml, P >
      0.05). The rate of bacteria translocation in the liver, kidney and mesenteric
      lymph was much higher in the BDL group than in other two groups. The rate of
      bacteria translocation in mesenteric lymph was 64.29%, significantly higher than
      that in the SO group and the rhGH group (P < 0.05). There was no significant
      difference in bacteria translocation rate between the SO group and the rhGH group
      (P > 0.05). Under an electron microscope, ileum mucosa epithelial cells in the
      BDL group were necrotic, and organelle were markedly metamorphic. In the rhGH
      group, ultrastructural changes were less evident or similar to those in the SO
      group. CONCLUSION: rhGH has significant protective effects on intestinal mucosa
      barrier in obstructive jaundice, and reduces intestinal translocation of bacteria
      and endotoxin.

PMID- 16109535
TI  - Comparison of Wirsung-jejunal duct-to-mucosa and dunking technique for
      pancreatojejunostomy after pancreatoduodenectomy.
AB  - BACKGROUND: Pancreato-enteric reconstruction after pancreatoduodenectomy (PD) is
      still a source of debate because of the high incidence of complications. Among
      the various types of pancreato-jejunostomies we don't know yet which is the best
      in terms of anastomotic failure and related complications rates. Wirsung-jejunal
      duct-to-mucosa anastomosis (WJ) and "dunking" pancreato-jejunal anastomosis (DPJ)
      are the two most used ones worldwide but conflicting results are reported. To
      determine which is the safer anastomosis and to define when an anastomosis should
      be preferred, we retrospectively reviewed two groups of patients who underwent WJ
      or DPJ. METHODS: Twenty-three patients underwent PD with WJ (n = 17) with dilated
      (WJD) (n = 9) or not-dilated Wirsung's duct (WJND) (n = 8) or with a DPJ (n = 6)
      over a 3-year period at a single institution. RESULTS: The complications rate was
      high in all groups of patients (33.3% in WJD, 37.5% in WJND and 66.7% in DPJ). A
      pancreatic fistula developed in one patient in each group (11.1% in WJD, 12.5% in
      WJND and 16.7% in DPJ). All these patients were managed conservatively.
      Anastomotic disruption took place in the WJ patients especially in the WJND group
      (n = 2) compared to the WJD (n = 1) (25% vs. 11.1%) or DPJ groups (0%): these
      three patients required a re-operation. Overall, the anastomotic defects were
      higher in patients who underwent WJND (37.5%), compared to WJD (22.2%) and to DPJ
      (16.7%). However, no statistical differences were found among the groups. Delayed
      gastric emptying (DGE) and total parenteral nutrition (TPN) along with
      anastomotic defects were responsible for a prolonged hospital stay. CONCLUSIONS:
      Our results were not able to demonstrate any statistical difference between the
      two different techniques in preventing anastomotic failure. WJ can represent a
      valid choice in case of a dilated duct and a firm, fibrotic enlarged gland that
      could not be properly invaginated in a small jejunal loop. DGE may occur in those
      patients who experienced an anastomotic failure and required a TPN regimen with a
      prolonged hospital stay.

PMID- 16109536
TI  - Diagnosis and treatment of solid-pseudopapillary tumors of the pancreas.
AB  - BACKGROUND: Solid-pseudopapillary tumors (SPTs) of the pancreas have been
      reported as rare lesions with "low malignant potential" occurring mainly in young
      women. This study was designed to define the clinicopathological characteristics
      and the effect of surgical intervention. METHODS: A retrospective clinical
      analysis was made of 21 patients with solid-pseudopapillary tumor of the pancreas
      admitted from June 1994 to December 2004. RESULTS: Abdominal pain as the major
      complaint was found in 13 patients, and palpable abdominal mass in 7. Imaging
      examination showed the abdominal mass clearly, but diagnosis was not defined. In
      12 patients, tumors were located in the pancreatic head and in 9 patients, in the
      pancreatic tail. The average diameter of the tumor was 9.5 cm (range, 3-20 cm).
      One patient had liver metastasis. The diagnosis of the tumor was proved
      pathologically during operation in 14 patients, and other 3 patients who had been
      diagnosed as having insulinoma and other malignant tumors were confirmed by
      paraffin section and enzyme labeling after operation. Eighteen patients (85.7%)
      were followed up with a median period of 24 months, 1-60 months without tumor
      recurrence. CONCLUSION: Huge pancreatic masses of the pancreas in young women are
      suggestive of solid-pseudopapillary tumors. Aggressive surgical therapy can
      result in good prognosis in these patients.

PMID- 16109537
TI  - Interleukin-1alpha, 6 regulate the secretion of vascular endothelial growth
      factor A, C in pancreatic cancer.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF, namely VEGF-A) is an
      angiogenic polypeptide and VEGF-C is a lymphangiogenic polypeptide that has been
      implicated in cancer growth, invasion and metastasis. Several cytokines and
      growth factors play an important part in cancer progression. These cytokines and
      growth factors are the principal mediators of cancer cells--stromal cell
      interaction, which is critical for invasion of cancer cells to the surrounding
      tissues and metastatic dissemination to distant organs. In this study, we studied
      VEGF-A, C expression in cultured human pancreatic cancer cell lines and whether
      the presence of VEGF-A, C in the cell lines is regulated by cytokines interleukin
      1alpha(IL-1alpha), and interleukin-6 (IL-6). METHODS: We used Northern blot and
      Western blot methods to analyze expression of the gene and protein of VEGF-A, C
      in all 6 tested cell lines (ASPC-1, CAPAN-1, MIA-PaCa-2, PANC-1, COLO-357 and
      T3M4) respectively. To analyze what is the regulator for this VEGF-A, C
      expression in pancreatic cancer, we used the reverse transcription-polymerase
      chain reaction (RT-PCR) method to analyze VEGF-A, C expression in cultured human
      pancreatic cancer cell lines (CAPAN-1 and COLO-357) under the stimulation with IL
      1alpha(10 microg/L) or IL-6 (100 microg/L). RESULTS: Northern blot analysis
      revealed the presence of the 4.1 kb VEGF-A mRNA transcript and 2.4-kb VEGF-C mRNA
      transcript in all 6 tested cell lines. Immunoblotting with highly specific anti
      VEGF-A, anti-VEGF-C antibody revealed the presence of a molecular weight of 43
      kDa VEGF-A protein and 55-kDa VEGF-C protein in all the cell lines. RT-PCR
      analysis revealed the levels of the VEGF-A and VEGF-C gene were 1-2 fold and a 1
      fold increase in the COLO-357 cell line by stimulation with IL-1alpha, however,
      no effect was found in the CAPAN-1 cell line. The levels of the VEGF-A and VEGF-C
      gene were 2-5 fold and a 1-fold increase in the CAPAN-1 cell line by stimulation
      with IL-6, but no effect was found in the COLO-357 cell line. CONCLUSION: These
      findings suggested that the expression of VEGF-A, C and their regulation by IL
      1alpha, IL-6 in pancreatic cancer contributes to the lymphatic and distant
      metastasis and the disease progression.

PMID- 16109538
TI  - Cystadenocarcinoma of the liver: a case report.
AB  - BACKGROUND: Biliary cystadenocarcinoma as a very rare hepatic neoplasm may be
      difficult to distinguish from simple hepatic cysts, especially in the unilocular
      form. Although diagnosis of cystadenocarcinoma during open hepatic surgery
      demands a complete surgical resection, few reports described the correct approach
      to such lesions revealed by laparoscopic approach. Five cases of incidental
      cystadenocarcinoma after laparoscopic surgery for hepatic cystic lesions were
      presented with discussion of diagnostic and management implications. METHODS:
      Clinical records of 5 patients who had undergone operation and histological
      examination at our hospital from 1993 to 2002 were analyzed retrospectively.
      RESULTS: In all patients who received liver lobectomy, primary hepatic
      cystadenocarcinoma was diagnosed. Primary biliary cystic neoplasm was difficult
      to diagnose and the management of both benign and malignant tumors was similar in
      the 5 patients. CONCLUSIONS: Cystadenocarcinoma is often difficult to diagnose
      because its clinical manifestations are similar to those of hepatic cysts and
      other cystic lesions. Imagining examination is helpful in evaluating the disease.
      Complete excision of cystadenocarcinoma with a wide margin is the best treatment.

PMID- 16109539
TI  - Symptomatic adult annular pancreas: report of two cases and a review of the
      literature.
AB  - BACKGROUND: Annular pancreas in adults is a rare embryologic abnormality detected
      after development of complications. Embryology, diagnosis and treatment
      strategies for symptomatic adult annular pancreas remain controversial. In this
      paper we reevaluated these problems in view of the technological and theoretical
      advances. METHODS: In 2 patients with annular pancreas, one(36-year-old male
      patient) presenting with duodenal obstruction and duodenal ulcer associated with
      duodenocolic fistula underwent Billroth II gastrectomy and fistula ectomy and the
      other(17-year-old male patient) presenting with duodenal obstruction and duodenal
      ulcer underwent Billroth II gastrectomy. English language literature about
      annular pancreas etiology, diagnosis and treatment was reviewed. RESULTS: Both of
      the patients had uneventfully recovered. Abdominal computed tomography,
      endoscopic retrograde cholangiopancreatography and magnetic resonance
      cholangiopancreatography showed typical images of annular pancreas. Duodenal
      bypass procedure, choledochojejunostomy, endoscopic sphincterotomy or biliary
      stenting, and pancreatic resection were alternative to treat this sort of
      anomaly. CONCLUSIONS: Annular pancreas in adults is a rare congenital
      abnormality, while newer imaging modalities and an index of suspicion may assist
      in finding more cases. The management of this congenital anomaly should be
      individualized according to the associated complications.

PMID- 16109540
TI  - Celiomesenteric trunk demonstrated by 3-dimensional contrast-enhanced magnetic
      resonance angiography.
AB  - BACKGROUND: Celiomesenteric trunk is a rare vascular anomaly, which has
      significant clinical implications. 3-dimensional contrast-enhanced magnetic
      resonance angiography (3D CE MRA) is a new imaging modality, non-invasive, fast
      and easy to perform. We describe a patient with a common celiomesenteric trunk
      demonstrated by 3D CE MRA. METHODS: A 45-year-old man was subjected to 3D CE MRA
      before transarterial chemoembolization (TACE) for hepatocellular carcinoma. The
      examination was performed on a 1.5T MR imager with a body coil. The contrast
      medium was gadopentetate dimeglumine. Source images from the hepatic arterial
      phase acquisition were reconstructed into MRA images. Intra-arterial digital
      subtraction angiography (DSA) during TACE was carried out 3 days after 3D CE MRA.
      RESULTS: On 3D CE MRA, a common trunk of the celiac and superior mesenteric
      artery was clearly depicted. The origin and course of the hepatic, splenic and
      superior mesenteric arteries were also visualized. These findings were confirmed
      by intra-arterial DSA. CONCLUSIONS: Celiomesenteric trunk can be well delineated
      by 3D CE MRA. The image is correlated precisely with that from DSA.

PMID- 16109541
TI  - Event-related potential of facial expression processing.
AB  - OBJECTIVE: To investigate spatial and temporal patterns of event-related
      potentials (ERP) evoked by facial expression. METHODS: ERP was recorded in 25
      healthy subjects while they performed facial recognition task. Repeated-measure
      one-way ANOVA was adopted to compare the subjects' responses to stimulation by 3
      different expressions (positive, neutral and negative) with statistical
      parametric mapping (SPM). RESULTS: Significant facial expression effects occurred
      separately in the left parietal and bilateral occipital regions (280-340 ms),
      left frontal region (400-420 ms), and right prefrontal region (480-500 ms). In 4
      time periods, significant difference was observed between positive and neutral
      emotion wave in the right frontoparietotemporal and left prefrontal regions (60
      80 ms), right occipital region (120-140 ms), left occipital region (280-320 ms),
      and left frontoparietal region (400-440 ms). Significant difference between
      negative and neutral emotion waves was observed in 5 time periods in the right
      occipital region (120-140 ms), central frontoparietal region (220-240 ms),
      central parietal region (280-300 ms), left parietal and right temporopartial
      regions (320-340 ms) and frontopartial occipitotemporal region (480-500 ms).
      CONCLUSIONS: The spatiotemporal patterns of ERP suggest that the information
      processing of facial expression involves extensive brain regions dynamically.

PMID- 16109542
TI  - Experimental study of thalidomide for treatment of murine hepatocellular
      carcinoma.
AB  - OBJECTIVE: To study the therapeutic effect of thalidomide (Tha) on murine
      hepatocellular carcinoma. METHODS: In murine transplanted hepatoma model,
      thalidomide was administered intragastrically alone (200 mg/kg daily for 10 days)
      or in combination with doxorubicin. The antitumor activity of Tha was observed in
      solid and ascitic tumor models. RESULTS: Tha induced significant growth
      inhibition of solid hepatoma without obvious toxicity on peripheral blood cells
      and lymphocyte proliferation. Although Tha alone had no effect on the survival of
      mice with ascitic tumor, it showed a synergistic antitumor activity in
      combination with doxorubicin (Dox) in both solid and ascitic tumor models.
      Moreover, Tha reduced Dox-induced cytopenia and immunosuppression. Histological
      analysis of Tha-treated tumors revealed remarkably enhanced tumor necrosis and
      lymphocyte infiltration on the edge of tumor tissues. CONCLUSION: Tha has
      definite therapeutic effect on murine hepatoma, and the combination with Dox
      shows an enhanced therapeutic potential.

PMID- 16109543
TI  - [Gene expression profiling of peripheral leukocytes from patients with systemic
      lupus erythematosus using oligonucleotide DNA microarray].
AB  - OBJECTIVE: To identify the differentially expressed genes in systemic lupus
      erythematosus (SLE) by comparing the gene expression profiles of peripheral
      leukocytes between SLE patients and healthy controls. METHODS: The total RNA was
      extracted from 5 ml peripheral blood of normal subjects and SLE patients, and
      reversely transcribed in cDNA templates to synthesize cDNA probes labeled for
      hybridization with the microarray. RESULTS: Totally 89 over- or under-expressed
      genes were identified in 9 SLE patients as compared with the controls. These
      genes included genes associated with cytokines and their receptors, immunity,
      cell signal transduction, protein transcription and synthesis, ion channel and
      transporters, cell apoptosis, DNA and RNA processing, and extracellular matrix
      etc. Clustering analysis showed that in spite of the individual diversity of the
      SLE patients, their gene expression profiles were strikingly similar. CONCLUSION:
      The differentially expressed genes screened with oligonucleotide DNA microarray
      technique may provide clues for exploring the pathogenesis and progression of
      SLE, and for identification of potential molecular markers for diagnosis and
      development of therapeutic drugs.

PMID- 16109544
TI  - [Receptor-related mechanism of proliferation inhibilion and apoptosis induetion
      of human tongue squamous cell line Tca8113 by retinoids].
AB  - OBJECTIVE: To investigate the receptor-related mechanism of retinoids inhibiting
      proliferation and inducing apoptosis of human oral squamous cell carcinoma cell
      line Tca8113. METHODS: The effects of 3 retinoids (namely 9-cis-RA, at-RA and 13
      cis-RA), TTNPB (RAR agonist) and methoprene acid (Ma, RXR agonist) on
      proliferation and cell cycle of Tca8113 cells were analyzed by MTT assay and flow
      cytometry. The roles of these agents in inducing apoptosis of Tca8113 cells were
      also evaluated by detecting the expression of Bcl-2/Bax, TUNEL and active caspase
      3 analysis. RESULTS: Both retinoids and TTNPB could inhibit the proliferation of
      Tca8113 cells, and the effect of TTNPB was the most powerful in all the reagents,
      but MA had no such effect. At the concentration of 1 x 10(-5) mol/L, all the
      agents except for Ma could increase the percentage of G(1)/G(0)-stage cells after
      incubation of the cells for 24 h and 48 h. Retinoids and TTNPB could up-regulate
      the expression of Bax and down-regulate Bcl-2 expression. The results of TUNEL
      demonstrated that retinoids and TTNPB, but not Ma, could induce apoptosis of
      Tca8113 cells as compared with the control group (P<0.05). Except for Ma, all the
      agents up-regulated caspase-3 expression, and the effect of TTNPB was the
      strongest (P<0.05). CONCLUSIONS: Retinoids can suppress the proliferation of and
      induce apoptosis of Tca8113 cells, the effect of which involves activation of RAR
      but not RXR. caspase-3 pathway is involved in apoptosis-inducing effects of
      retinoids.

PMID- 16109545
TI  - [Differential expression of 63 novel genes located on chromosome 3p21-22 in
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To identify novel genes that may participate in the pathogenesis of
      nasopharyngeal carcinoma (NPC). METHODS: Sixty-three single copies of expressed
      sequence tag (EST) clusters mapped in the region of D3S1609-D3S1295 on chromosome
      3p21-22 were obtained and assembled into long or full-length cDNA consensus
      sequence by in silico cloning strategy. Accordingly, these unigene consensus were
      studied by semi-quantitative reverse transcriptional (RT)-PCR with poorly
      differentiated squamous cell carcinoma tissues from 32 patients with primary
      nasopharyngeal carcinoma (NPC) and inflammatory tissues from 1b noncancerous
      individuals with chronic nasopharyngitis, as well as 4 NPC cell lines
      (CNE1bCNE2bHNE1 and HNE2). RESULTS: Forty-nine unigene ESTs were expressed
      equally in both NPC and NP, 8 were expressed neither in NPC nor in NP, 2 had
      higher expression in NPC than in NP, and 4 had lower expression (or undetectable)
      in NPC than in NP. The expression of Hs.27566 gene was detected in none of the
      NPC cell lines, and was significantly reduced or undetectable in NPC biopsies in
      comparison with NP (P<0.001). CONCLUSION: The differential expression of 63 novel
      genes located on chromosome 3p21-22 in NPC is mapped and 6 novel genes with
      differential expression in NPC tissues are identified.

PMID- 16109546
TI  - [Specific killing effects of adenovirus-mediated double suicide gene driven by
      KDR promoter on venous endothelial cells and gastric cancer cells in vitro].
AB  - OBJECTIVE: To study the specific killing effect of adenovirus(Ad)-mediated double
      suicide gene under regulation by KDR promoter on gastric cancer cells and venous
      endothelial cells in vitro. METHODS: KDR-expressing MGC803 and ECV304 cells and
      non-KDR-expressing LS174T cells were infected by the two Ads (AdEasy-KDR-CDglyTK
      and AdEasy-CMV- CDglyTK), and expression of CDglyTK was detected by reverse
      transcriptional (RT) PCR. After treatment with 5-FC and GCV, the killing effects
      of the double suicide genes on various cells were evaluated. RESULTS: The
      infection rate of the two resultant recombinant Ads did not differ significantly
      in the cells. RT-PCR demonstrated the presence of CDglyTK gene product in all the
      cells infected by Ad-CMV-CDglyTK and all but SL147T cells infected by Ad-KDR
      CDglyTK. All the cells infected by Ad-CMV-CDglyTK and ECV304 and MGC803 cells
      infected Ad-KDR-CDglyTK were highly sensitive to the prodrugs. In contrast,
      LS174T cells infected by Ad-KDR-CDglyTK did not appear sensitive to the two
      prodrugs (P<0.001). In addition, the effect of the double suicide gene was much
      stronger than that of either of the single suicide gene (P<0.001), showing also
      considerable bystander effect. CONCLUSIONS: The double suicide gene driven by KDR
      promoter has specific killing effect on KDR-expressing gastric tumor cells and
      venous endothelial cells in vitro.

PMID- 16109547
TI  - [Changes of the new gaseous transmitter H2S in patients with coronary heart
      disease].
AB  - OBJECTIVE: To investigate the changes of plasma hydrogen sulfide (H(2)S) in
      patients with coronary heart disease (CHD). METHODS: Plasma H(2)S levels were
      measured in 40 patients with CHD and 17 angiographically normal patients by
      sulfide-sensitive electrodes, and the variation of plasma H(2)S levels was
      analyzed in different clinical types of CHD and in different types of coronary
      artery lesions. The association of plasma H(2)S levels with the risk factors of
      CHD was also analyzed. RESULTS: Plasma H(2)S levels were significantly lowered in
      CHD patients in comparison with that in angiographically normal control subjects
      (26.10+/-14.27 micromol/L vs 51.74+/-11.94 micromol/L, P<0.001). In CHD patients,
      plasma H(2)S levels in unstable angina patients (UAP, 23.60+/-14.41 micromol/L)
      and acute myocardial infarction patients (AMI, 19.98+/-7.516 micromol/L) were
      significantly lower than that in stable angina patients (SAP, 38.41+/-14.53
      micromol/L, P<0.05). No significant difference in plasma H(2)S levels was found
      between CHD patients with double-vessel and multi-vessel lesions (16.91+/-7.98 vs
      18.39+/-7.78 micromol/L, P>0.05), but the two groups of patients had
      significantly lower plasma H(2)S levels than patients with single-vessel
      involvement (33.04+/-15.01 micromol/L, P<0.05 and P<0.01, respectively). Plasma
      H(2)S level was significantly lower in CHD patients with coronary artery
      occlusion than in patients with simple stenosis (19.04+/-9.55 vs 28.24+/-14.85
      micromol/L, P<0.05). Among the CHD patients, H(2)S levels were significantly
      lower in smokers than in non-smokers (27.54+/-10.37 vs 32.24+/-15.77 micromol/L,
      P<0.05), also lower in hypertensive patients than in normotensive patients
      (20.36+/-8.69 vs 33.77+/-15.86 micromol/L, P<0.01). Plasma H(2)S levels showed a
      significant inverse correlation with blood glucose (r=-0.493 6, P=0.001 6), but
      there were no significant correlations with sex, age, cholesterol, triglyeride,
      TC, low-density lipoprotein, high-density lipoprotein, or body mass index.
      CONCLUSION: Decreased plasma H(2)S levels may correlate with the severity of CHD
      and changes of the coronary artery, and may implicate the risk factors of CHD
      such as smoking, hypertension, and high blood glucose.

PMID- 16109548
TI  - [Effects of intrahippocampal microinjection of motilin on interdigestive
      migrating myoelectrical complexes of rat duodenum].
AB  - OBJECTIVE: To explore the effects of intrahippocampal injection of motilin on
      interdigestive migrating myoelectrical complex (MMC) of rat duodenum. METHODS:
      Adult SD rats of either sex were subjected to injection of 0.5 microl motilin
      (0.74 nmol/microl) through the guiding cannula stereotaxically implanted into the
      hippocampus previously. Interdigestive MMC of the duodenum was recorded by
      RM6240B multilead physiological recording system. RESULTS: After motilin
      injection into the hippocampus, duodenal MMC cycle was significantly shortened,
      but the amplitude and frequency of phase III were increased without affecting the
      duration of phase III. The effect of motilin injection into the hippocampus on
      MMC was completely abolished by subdiaphragmal vagotomy but not affected by
      intravenously injected atropine, phentolamine or propranolol. Anti-motilin serum
      could partly abolish the effects of motilin on MMC. CONCLUSIONS: Motilin
      injection into the hippocampus have effects on the duration of duodenal MMC cycle
      and the amplitude and frequency of phase III, which may rely on the effect of
      noncholinergic and nonadrenergic neurons on duodenal smooth muscle or the
      increase of local motilin via hippocampus-hypothalamus-brain stem-vagus pathway.
      The hippocampus plays an important role in duodenal MMC.

PMID- 16109549
TI  - [In vitro culture and identification of tolerogenic dendritic cells from mouse
      bone marrow].
AB  - OBJECTIVE: To establish a simple and economic method for in vitro culture of
      tolerogenic dendritic cells (Tol-DC) from mouse bone marrow to facilitate further
      research of the application of Tol-DC in autoimmune disease. METHODS: The
      dendritic cells were derived from in vitro culture of the precursor cells from
      mouse bone marrow with recombinant mouse granulocyte-macrophage colony
      stimulating factor (rmGM-CSF) and interleukin (IL)-4, respectively. Eighteen
      hours before completion of cell culture, lipopolysaccharide (LPS) was added in
      the medium for stimulating rmGM-CSF-treated cells, but not IL-4-treated cells.
      The cells were collected on day 6, and the cell morphology, phenotype and
      immunofunction were analyzed. RESULTS: DC cultured in vitro had a CD11c(+)
      expression rate of 76.67% with typical morphology. The DCs without LPS treatment
      were characterized by moderate expression of class II major histocompatibility
      complex (MHCII) and low expression of costimulatory molecules, while those with
      LPS treatment had high expressions of MHCIIand costimulatory molecules.
      CONCLUSION: Immature tolerogenic DCs can be derived in large quantity using this
      method with the potential for use in the treatment of autoimmune diseases.

PMID- 16109550
TI  - [Human lung epithelial cells produce interleukin-8 through protease-activated
      receptor 1].
AB  - OBJECTIVE: To investigate the actions of protease-activated receptor 1 (PAR1)
      agonists and thrombin on the secretion of interleukin-8 (IL-8) from human lung
      epithelial cells. METHODS: A549 cells were cultured in a 12-well culture plate.
      The challenge was performed by addition of various concentrations of PAR1 agonist
      peptides SFLLR and its reverse peptides RLLFS, thrombin or hirudin, a thrombin
      inhibitor, into each well, respectively. After 2 or 16 h, the reactions were
      terminated by removal of the supernatant from each well. A sandwich enzyme-linked
      immunosorbent assay (ELISA) was used to determine the levels of IL-8 in the
      supernatants. RESULTS: Following a 16-hour incubation, SFLLR was able to induce
      concentration-dependent secretion of IL-8. The maximum release of IL-8 was
      increased nearly 16 fold more than the baseline release. The reverse PAR1
      agonists had little effects on IL-8 release. Thrombin was also able to induce
      concentration- dependent secretion of IL-8. As low as 1 kU/L thrombin was able to
      induce IL-8 release from the epithelial cells, and the maximum accumulated
      release of IL-8 was observed with 10 kU/L thrombin, which was 7.5 fold the
      baseline release. Thrombin inhibitor hirudin could inhibit thrombin-induced
      secretion of IL-8. The time course showed that the actions of PAR1 agonist
      peptides SFLLR and thrombin initiated at 2 h and reached the peak at 16 h.
      CONCLUSION: PAR1 agonist peptides and thrombin are potent secretogogues of IL-8
      release from cultured human lung epithelial cells, and PAR1 antagonists and
      thrombin inhibitor may possess the ability to inhibit airway inflammation.

PMID- 16109551
TI  - [Effects of angiotensin receptor blocker and angiotensin-coverting enzyme
      inhibitor on vascular endothelial function in type 2 diabetic patients with
      atherosclerosis: a comparative study].
AB  - OBJECTIVE: To compare the changes of endothelial function in type 2 diabetic
      patients with atherosclerosis (AS) after treatment with angiotensin-coverting
      enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB). METHODS:
      Totally 145 type 2 diabetic patients with AS were included in this study.
      According to completely randomized open unbalanced design, the patients were
      assigned into ACEI group (n=99) with ramipril treatment (starting dose of 2.5
      mg/d and gradually reaching 5 mg/d), ARB group (n=25) with irbesartan treatment
      (with gradual increase of doses till reaching the maximum daily dose of 150 mg),
      and control group (n=21) without the above medication. After a treatment lasting
      for 3 months, the brachial artery endothelial function was evaluated with two
      dimensional ultrasonography. RESULTS AND CONCLUSIONS: After therapy, endothelium
      dependent vasodilation (EDV) of the brachial artery increased from (3.55+/-2.80)%
      to (5.62+/-4.18)% (P=0.001), and endothelium-independent vasodilation (EIV)
      increased from (12.62+/-7.48)% to (12.80+/-7.04)% (P=0.835) in ACEI group. EDV
      increased from (4.42+/-2.95) % to (6.28+/-3.26)% (P=0.039), while EIV decreased
      from (10.69+/-5.85)% to (9.54+/-4.78)% (P=0.229) in ARB group. No statistical
      changes in the indices were found after therapy in the control group (P>0.05).
      Comparison of endothelial function in the 3 groups showed no statistical
      significance in the changes of EDV between ACEI and ARB groups (P=0.853). No
      differences were found in the change of EIV in the 3 groups (P=0.644). The
      therapy with 150 mg irbesartan and 5 mg ramipril for 3 months produces similar
      effects on the endothelial function in these patients.

PMID- 16109552
TI  - [Effects of all-trans-retinoic acid, acitretin and tazarotene on apoptosis and
      Bax/Bcl-2 expressions of human melanoma cells A375 and the significance].
AB  - OBJECTIVE: To investigate the effects of all-trans retinoic acid (ATRA),
      acitretin and tazarotene on apoptosis and Bax/Bcl-2 protein expressions of human
      melanoma A375 cells. METHODS: The effects of retinoids on apoptosis and Bax/Bcl-2
      protein expressions of A375 cells in vitro were examined. Apoptosis analysis with
      double staining with annexin V-FITC and PI was performed using flow cytometer.
      SABC immunocytochemistry was employed for detection of Bax/Bcl-2 protein
      expressions. RESULTS: At the concentration of 1 x 10(-5) mol/L, ATRA, acitretin
      and tazarotene all induced apoptosis of A375 cells with apoptosis ratio of 5.03%
      (P<0.05), 13.42% (P<0.05) and 2.88% (P>0.05), respectively, and acitretin induced
      more significant apoptosis than the other two agents (P<0.05). In addition, all
      the three agents significantly increased the number of cells positive for Bax
      expression and decreased the number of cells expressing Bcl-2 (P<0.05), among
      which acitretin had the strongest effects. CONCLUSIONS: ATRA, acitretin and
      tazarotene mediate apoptosis of A375 cells possibly through, at least partially,
      the mitochondrial pathway. Acitretin may be utilized as a valuable alternative
      for treating melanoma.

PMID- 16109553
TI  - [Killing effect of Photofrin-Herceptin immunoconjugate on tumor cell lines in
      vitro].
AB  - OBJECTIVE: To study the specific killing effect of the Photofrin-Herceptin
      immunoconjugate on the tumor cells expressing HER-2. METHODS: Photofrin (porfimer
      sodium) was covalently coupled to Herceptin (trastuzumab) via [1-ethyl-3-(3
      dimethyl-aminopropyl)carbodiimide hydrochloride](EDCI) , and the killing effect
      of this conjugate was evaluated by means of MTT assay on SK-BR-3, MCF-7 and A549
      cell lines expressing HER-2 at different levels. RESULTS: The conjugate had
      weaker immunoactivity than Herceptin, but possessed stronger killing effect on
      the cell lines expressing HER-2 than Photofrin, Herceptin, as well as the mixture
      of Photofrin and Herceptin (P<0.05). In the cell lines negative for HER-2
      expression, the killing effect of the conjugate was similar to that of Photofrin,
      Herceptin, and their mixture. CONCLUSION: Photofrin-Herceptin immunoconjugate can
      specifically kill HER-positive cells in vitro.

PMID- 16109554
TI  - [Role of ciliary neurotrophic factor in regeneration of severed facial nerve of
      cats].
AB  - OBJECTIVE: To study the role of extrinsic (CNTF) in the regeneration of severed
      facial nerve in cats. METHOD: The facial nerve in temporal bone of adult cats
      were severed and the severed ends were connected with CNTF or saline applied at
      the connection. Electrophysiological examination and immunocytochemistry were
      performed with immunoelectron microscope for morphological analysis at 2, 4 and 8
      weeks after the operation. RESULTS: Two weeks after operation, both CNTF and
      saline groups failed to exhibit muscular excitement by facial nerve stimulation,
      but the amount of myelinated nerve fibers had statistical difference between the
      two groups (P<0.05). At 4 weeks, the latency of the facial muscle excitement was
      7.832+/-2.695 ms in CNTF group and 16.120+/-3.516 ms in saline group, and the
      average number of myelinated axons was significantly different between the two
      groups (1,435+/-318 vs 957+/-269, P<0.05). At the 8th weeks, the latency of
      facial muscle excitement was reduced to 3.125+/-0.165 ms in CNTF group and to a
      comparable level of 3.095+/-0.178 ms in saline group (P>0.05), and the average
      number of myelinated axons increased to 1,695+/-283 and 1,543+/-320 respectively
      in the two groups (P>0.05). Significant increase of Schwann cells was noted in
      both groups at this stage. CONCLUSION: Local application of CNTF may enhance
      facial early-stage nerve regeneration in adult cats, but its long-term effects
      remain unclear.

PMID- 16109555
TI  - [Apoptosis of pulmonary epithelial cells and endothelial cells in mice exposed to
      phosgene].
AB  - OBJECTIVE: To study apoptosis of pulmonary epithelial cells and endothelial cells
      in mice with pulmonary edema induced by phosgene exposure. METHODS: Thirty-two
      mice were divided into normal group and phosgene group with 16 mice in each
      group. The mice in phosgene group were exposed to phosgene (11.9 mg/L) for 5 min
      and those in the control group to air. Four hours after exposure, alveolar type
      II cells were isolated and cultured to observe their apoptosis by electron
      microscope and flow cytometry. The lung tissues were also taken for DNA gel
      electrophoresis and TUNEL assay. RESULTS: Apoptotic bodies were observed in
      alveolar type II cells under electron microscope in phosgene group, which had
      higher cell apoptosis rate than the control group [(40.26+/-7.74)% vs (1.58+/
      1.01)%, P<0.001] as determined by flow cytometry. Ladder-like DNA fragmentation
      pattern was observed in DNA gel electrophoresis in phosgene group with apoptosis
      of the pulmonary epithelial and endothelial cells observed by TUNEL. CONCLUSIONS:
      Phosgene can induce pulmonary epithelial and endothelial cell apoptosis in mice,
      suggesting that the mechanism of phosgene-induced pulmonary edema involves
      apoptosis of the lung cells.

PMID- 16109556
TI  - [Effects of dexamethasone on the expression of muscarinic receptor mRNA in
      asthmatic guinea pig airway smooth muscle and eosinophil infiltration in
      bronchoalveolar lavage fluid].
AB  - OBJECTIVE: To investigate the effect of dexamethasone on the expression of
      muscarinic receptor (MR) mRNA in smooth muscle and infiltration of eosinophils
      (Eos) in the airway of asthmatic guinea pigs. METHODS: Thirty healthy guinea pigs
      were randomized into 3 equal groups, the control group, asthmatic group and
      dexamethasone therapy group. Asthma was induced in the latter 2 groups with the
      asthma-inducing agents and received treatments as indicated. Bronchial alveolar
      lavage fluid(BALF) were collected subsequently from the guinea pigs for examining
      the total cell number and cell classification, and histopathologic examination of
      the lung tissue was performed. Semi-quantitative analysis with reverse
      transcriptional- polymerase chain reaction (RT-PCR) was performed for M(2) and
      M(3) receptor mRNA in airway smooth muscle. RESULTS: Compared with the control
      and the asthmatic group, the number of Eos in the BALF of dexamethasone therapy
      group was significantly lower (P<0.01). In spite of the presence of hyperemia and
      edema in the lung tissues of the dexamethasone therapy group, Eos infiltration
      was less severe than that in the asthmatic group. As found by RT-PCR, the
      quantity of M(2) receptor mRNA in the airway smooth muscle of the dexamethasone
      therapy group was significantly higher than those in both the control and
      asthmatic groups (P<0.01), and the quantity of M(3) receptor mRNA in the airway
      smooth muscle of dexamethasone therapy group was significantly higher than that
      in the asthmatic group, but did not significantly differ from that in the control
      group. The quantities of M(2) and M(3) receptor mRNAs in the control group were
      both significantly higher than that in asthmatic group (P<0.01). CONCLUSION: The
      expression of M(2) receptor is increased in antigen- challenged guinea pigs, and
      that of M(3) receptor decreased. Dexamethasone can treat asthma by inhibiting
      inflammatory action involving Eos infiltration, regulating the expressions of
      M(2) and M(3) receptors and restoring the function of M(2) receptor.

PMID- 16109557
TI  - [Expressions of tumor necrosis factor receptor I and II in human gastric
      carcinoma].
AB  - OBJECTIVE: To study the clinical significance of expressions of tumor necrosis
      factor receptor I and II(TNFR I and II) and their relationship with clinical
      pathology in human gastric carcinoma. METHODS: SABC immunohistochemical method
      was used to examine the expressions of TNFR I and II in 51 cases of gastric
      carcinoma, 41 adjacent mucosal and 15 normal gastric mucosa tissues. RESULTS: The
      positivity rates of TNFR I and II expressions in human gastric carcinoma were
      significantly higher than those in the adjacent mucosal and normal mucosal
      tissues, and their expressions were significantly higher in the surrounding
      mucosa than in the normal tissues. In gastric carcinoma tissues, no correlations
      of TNFR I and II expressions with serous membrane invasion or lymph node
      metastasis were found, but the differentiation grade was positively correlated
      with TNFR expressions (r=-0.3111, P=0.035; r=-0.5952, P=0.000, respectively).
      CONCLUSION: TNFR I and II expressions are valuable indicators for determining the
      malignancy and predicting the differentiation grade of gastric carcinoma.

PMID- 16109558
TI  - [A preliminary study of the homing capacity of allograft mesenchymal stem cells
      to rat liver].
AB  - OBJECTIVE: To study the homing capacity of allograft mesenchymal stem cells
      (MSCs) transfected with a green fluorescent protein (GFP) retroviral construct to
      the liver of rats. METHODS: MSCs were obtained from rat bone marrow and cultured
      in vitro in conditional DMEM medium supplemented with 10% fetal bovine serum. The
      MSCs were identified by the monoclonal antibodies of CD29, CD44, CD34, CD45,
      CD90, SH-2 and SH-3 followed by transfection with a GFP retroviral vector. After
      ex vivo expansion, the transfected MSCs were infused through the tail vein or
      portal veins of rats, some of which were subjected to treatment with carbon
      tetrachloride (CCl(4)) to induce centrolobular liver necrosis. On days 3 and 7
      after transplantation, the liver was removed from each recipient and evaluated
      for the presence of GFP transgene in purified genomic DNA using sensitive real
      time PCR. RESULTS: All the rats receiving GFP-labeled MSCs survived until the
      study had been completed. GFP transgene in purified genomic DNA were detected in
      the livers of all the rats with GFP-labeled MSC infusion by sensitive real-time
      PCR. DNA copy numbers of GFP in the liver were higher in rats with CCl(4)
      treatment than in those without the treatment. Infusion of the MSCs through the
      tail vein or the portal vein did not produce significant difference in the mean
      DNA copy number in the liver of CCl(4)-treated rats. In rats without CCl(4)
      treatment, the sites of MSC infusion, e.g. through the tail vein or the portal
      vein, produced significant difference in MSC homing to the liver, which was also
      related to the passage of time after MSC infusion. CONCLUSION: In rats with liver
      injuries induced CCl(4), the timing and number of MSCs homing to the liver might
      be closely related to the presence of liver injury, but not to the site of MSC
      infusion, e.g. through the tail vein or the portal vein. MSCs possess homing
      capacity to the liver in normal recipient rats, and number of homed MSCs is
      related to the site of infusion and post-transplantation time.

PMID- 16109559
TI  - [Value of quantitative examination of urine MUC1 in bladder transitional cell
      carcinoma].
AB  - OBJECTIVE: To evaluate the value of quantitative examination of MUC 1 in the
      urine of patients with bladder transitional cell carcinoma (BTCC). METHODS: Urine
      samples were obtained from 31 patients with BTCC for quantification of MUC 1
      content by immunoradiometric analysis. The urine samples were also examined in 10
      patients with cystitis glandularis, 10 with benign urine disease and 10 healthy
      volunteers. The differences in urine MUC1 content were statistically measured
      between the groups, between cancer patients of different clinical stages and
      classes, between primary and recurrent cancer patients, and between measurements
      taken before and after operation. RESULTS: Urine MUC 1 was detected in all the
      patients. No significant differences were found between the groups, nor between
      patients with BTCC in all stages (P>0.05), or between primary and recurrent
      cancer patients (P>0.05). But MUC 1 contents showed significant difference before
      and after the operation in the cancer patients (P<0.05). CONCLUSIONS: Urine MUC 1
      can not serve as the marker to screen and diagnose BTCC, but it can be useful in
      therapeutic effect and prognostic evaluation. Specific oncogene markers are more
      significant than oncogene phenotype markers in clinical diagnosis and screen of
      BTCC.

PMID- 16109560
TI  - [Effect of preoperative lymphatic chemotherapy on Bcl-2 and Bax expression in
      axillary metastasis of breast cancer].
AB  - OBJECTIVE: To observe the expression of Bcl-2 and Bax proteins and cell apoptosis
      induced by preoperative lymphatic chemotherapy with epirubicin-activated carbon
      suspension (Epi-CH) in the cells of axillary metastatic lymph node of breast
      cancer and investigate the mechanism. METHODS: Sixty patients with breast cancer
      of stages II-III were randomly divided into two groups. Forty patients in Epi-CH
      group were injected with 10 mg Epi-CH in the tissue around the primary tumor or
      biopsy excision 72 h before operation. Twenty patients in the control group were
      injected with 10 mg epirubicin solution in the same region. The stained lymph
      nodes full of tumor cells in Epi-CH group and the non-stained nodes in the
      control group were selected for apoptotic detection by TUNEL method. The
      expression of Bcl-2 and Bax proteins were examined by SP immunohistochemistry.
      RESULTS: The apoptotic index of the metastatic cancer cells in Epi-CH group was
      increased remarkably in comparison with that in the control group [(9.5+/-2.7) %
      vs (3.8+/-1.4) %, P<0.01). Compared with the control group, the expression of Bcl
      2 and Bax proteins were up-regulated significantly in Epi-CH group (P<0.05 and
      P<0.01, respectively), resulting in decreased ratio of Bcl-2/Bax. CONCLUSION:
      Lymphatic chemotherapy can promote cell apotosis in axillary metastasis of breast
      cancer, which may result from decreased ratio of Bcl-2/Bax.

PMID- 16109561
TI  - [Intraoperative and postoperative risk factors for surgical site infection
      following cesarean section].
AB  - OBJECTIVE: To investigate intraoperative and postoperative high-risk factors for
      surgical site infection after cesarean section. METHODS: We retrospectively
      reviewed cesarean section cases in terms of emergency operation, anesthesia
      methods, operating time, blood loss, hospital stay, surgical skills of the
      surgeon, and postoperative nursing care to identify the high risk-factors of
      surgical site infection during and after the operation. A retrospective case
      controlled study of all the parturients with postoperative surgical site
      infection was conducted. RESULTS: In the risk factors examined, anesthesia
      methods, operative time, and length of hospital stay showed significant
      differences between the two groups, while volume of blood loss and emergency
      operation did not. CONCLUSION: Effective measures need to be taken to eliminate
      the intraoperative and postoperative high-risk factors of surgical-site infection
      following cesarean section.

PMID- 16109562
TI  - [Clinical analysis of serum endothelin in type 2 diabetic patients with vascular
      complications].
AB  - OBJECTIVE: To explore the clinical significance of changes in urine microalbumin
      (UM) and endothelin (ET) in different courses of type 2 diabetes. METHODS: A
      clinical analyses of 30 type 2 diabetic patients with vascular complications
      (group A) was conducted in comparison with type 2 diabetic patients without
      vascular complications (group B) and patients with impaired glucose tolerance
      (IGT, group C). With 30 healthy subjects with family history of type 2 diabetes
      (group D) and 30 healthy subjects without such family history (group E) as
      controls, UM and ET were determined in all the subjects for a statistical
      analysis. RESULTS: Significant differences in UM content was noted between group
      A and the other 4 groups (P<0.05), while the content did not differ significantly
      between the latter 4 groups (P>0.05). ET content was significantly higher in
      group A than in the other 4 groups (P<0.01), and was the lowest in group E
      (P<0.01). CONCLUSIONS: Type 2 diabetic patients sustain extensively impaired
      endothelium function, which is exacerbated with the progression of the disease
      courses. Synchronized changes between vascular complications and impaired
      endothelium function indicates that vascular endothelial injury relates to
      vascular complications and the progression of diabetes.

PMID- 16109563
TI  - [Dynamic analysis of drug resistance of Pseudomonas aeruginosa in laboratory and
      clinical two-drug regimen].
AB  - OBJECTIVE: To analyze drug resistance status of Pseudomonas aeruginosa in the two
      drug regimens in laboratory and clinical settings for more appropriate
      application of antibiotics. METHODS: The laboratory data of drug resistance rate
      of Pseudomonas aeruginosa identified with Biomerieux Vitek 32 system were
      collected. The clinical two-drug regimen data corresponding to anti-microbial
      sensitivity test were investigated, and the resistance rate of the clinical two
      drug regimen was analyzed statistically. RESULTS: The isolation rate of
      Pseudomonas aeruginosa with multi-drug resistance increased steadily in recent
      years, and the resistance rate to 6 widely used antibiotics increased by over
      20%. Two Pseudomonas aeruginosa strains resistant to all the 6 drugs were
      identified in January 2004, and till June 2005, totally 18 panresistant strains
      had been isolated with dramatic increases in MIC value. In the clinical two-drug
      regimen, sulbactam/amikacin, sulbactam/ciprofloxacin, tazobactam/amikacin, and
      imipenem/amikacin still had low resistant rates. CONCLUSIONS: Multi-drug
      resistance of Pseudomonas aeruginosa to the antibiotics is a serious problem. A
      two-drug regimen based on anti-microbial susceptibility test should be chosen.

PMID- 16109564
TI  - [Effect of Yiyuan oral solution on immune function of normal mice].
AB  - OBJECTIVE: To study the effect of Yiyuan oral solution on the immune function of
      normal mice. METHOD: The mice were divided into control and 3 Yiyuan oral
      solution groups (at low, moderate and high doses). The immune indices of delayed
      type hypersensitivity, transformation of spleen lymphocyte, serum hemolysin,
      splenocytic antibody formation, carbon clearance index, phagocytotic function of
      the macrophage and natural killer cell activity were observed after
      administration of Yiyuan oral solution. RESULT AND CONCLUSION: Yiyuan oral
      solution can enhance the immune function of normal mice.

PMID- 16109565
TI  - [Construction of recombinant eukaryotic expression plasmid pcDNA3.1(+)-mtDNA of
      human colorectal carcinoma cells].
AB  - OBJECTIVE: To construct recombinant eukaryotic expression plasmid pcDNA3.1(+)
      mtDNA for investigation of mutations in the D-loop region of mitochondrial DNA in
      human colorectal carcinoma. METHODS: The D-loop region of 3 colorectal carcinoma
      cell lines (SW480, LoVo, and HT29) were amplified by PCR and sequenced. The mtDNA
      fragment was recombined in the eukaryotic expression plasmid pcDNA3. 1(+), and
      the resultant pcDNA3.1(+)-mtDNA recombinant was used to infect murine fibroblast
      cell line NIH3T3. RESULTS: Among the 3 colorectal carcinoma cell lines (SW480,
      LoVo, HT29), 10, 9, 8 mutations, were identified, respectively. The 1119-bp
      fragment of mtDNA was successfully cloned. DNA sequencing analysis demonstrate
      total agreement of the sequence with that in GenBank. The mtDNA fragments were
      cloned into the multiple cloning sites of vector pcDNA3.1(+) properly and the
      recombinant was introduced into NIH3T3 cells. CONCLUSIONS: The D-loop region of
      mitochondrial DNA is a highly polymorphoric and mutable region with high mutation
      rate in human colorectal carcinoma cells. The recombinant eukaryotic expression
      plasmid pcDNA3.1(+)-mtDNA is successfully constructed.

PMID- 16109566
TI  - [Expression of mineral-associated markers in human dental follicle cells in
      vitro].
AB  - OBJECTIVE: To culture human dental follicle cells in vitro and observe their
      mineralization characteristics. METHODS: Human dental follicle tissues were
      digested with bacterial collagenase and cultured to obtain dental follicle cells.
      Mineralization characteristics of these cells were identified by
      immunohistochemistry and reverse transcription (RT)-PCR. Dental follicle cells
      were incubated with mineralization-inducing agents to observe the formation of
      mineralized nodules. RESULTS: Immunohistochemistry staining revealed expressions
      of type I collagen, type III collagen, osteopontin and osteonectin in the
      cytoplasm of dental follicle cells cultured in vitro. Low levels of bone
      sialoprotein, osteocalcin and alkaline phosphatase mRNA were also detected by RT
      PCR. Mineralized nodules were observed after 20 days of incubation with
      mineralization-inducing agents with positivity for von-Kossa staining.
      CONCLUSION: Human dental follicle cells cultured in vitro show some features of
      osteoblasts or cementoblasts and can be used as the seed cells for periodontal
      tissue engineering.

PMID- 16109567
TI  - [Investigation of steroid sulfatase gene in two pedigrees with X-linked
      ichthyosis].
AB  - OBJECTIVE: To investigate the gene mutation in two pedigrees with X-linked
      ichthyosis (XLI) and explore the relationship between the mutation and clinical
      manifestations. METHODS: Genomic DNA of the affected and normal members of the
      pedigrees and 50 unrelated normal subjects from different regions was extracted
      with a whole blood genomic DNA extraction kit for use of the template for PCR
      amplification of exon 1, exon 2 and exon 10 of the steroid sulfatase (STS) gene.
      RESULTS: The STS gene was partially deleted in the affected members in the
      pedigrees with XLI, leaving only exon 1 but not the other exons. The normal
      member of the pedigree and 50 unrelated normal subjects had no such deletion.
      CONCLUSION: Partial deletion of the STS gene exists in the two pedigrees with
      XLI, which is responsible for pathological skin changes characteristic of XLI.

PMID- 16109568
TI  - [Effect of silicon and latex urinary catheters: a comparative study].
AB  - OBJECTIVE: To evaluate the effect of silicon and latex urinary catheters on
      urinary mucosa. METHODS: A randomized, controlled prospective clinical trial was
      carried out in 60 patients admitted in the Department of Neurosurgery, who
      required long-term use of an indwelling urinary catheter. The patients were
      divided into 2 equal groups with placement of silicon or latex urinary catheter,
      and routine laboratory urine test was performed on a regular basis and the
      patients feelings during catheter retention were recorded. RESULTS: Patients with
      placement of indwelling silicone catheters reported no obvious discomfort in
      relation to the catheter placement and had significantly lower incidence of
      hematuria identified microscopically than those with common latex catheters.
      CONCLUSION: Compared with latex catheters, silicone catheters cause less injuries
      and reduce substantially irritation of the urinary mucosa, and we suggest the use
      of silicone catheter in patients requiring long-term indwelling urinary
      catheters.

PMID- 16109569
TI  - [Digital subtraction angiography and preoperative embolization for meningiomas].
AB  - OBJECTIVE: To investigate the diagnostic value of digital subtraction angiography
      (DSA) and the clinical efficacy of preoperative embolization for miningiomas.
      METHODS: Fifty-eight patients with meningioma were examined by DSA, and
      preoperative embolization was performed in patients whose miningiomas were
      supplied predominantly by the external carotid artery (ECA). RESULTS: In 43
      patients, the meningiomas was exclusively or predominantly supplied by ECA, and
      the feeding arteries were embolized with particles of 250-350 microm through
      catherization of ECA. The blood supply of the tumor in 31 patients was completely
      blocked, and partial occlusion through embolization was performed in 12 patients.
      No complications in relation to the embolization occurred. Fifty-three patients
      underwent total removal of the meningiomas and the others had partial removal 1-7
      days following DSA and embolization, with tumor-associated intraoperative
      hemorrhage of 600 ml on average. CONCLUSION: DSA has important diagnostic value
      for meningiomas, and preoperative embolization can be safe and effective to
      reduce bleeding, shorten the operation time and prevent postoperative
      complications.

PMID- 16109570
TI  - [Analysis of different reperfusion methods for acute ST segment elevation
      myocardial infarction].
AB  - OBJECTIVE: To evaluate significance of different reperfusion methods in the
      treatment of acute ST segment elevation myocardial infarction (STEMI). METHODS: A
      retrospective analysis of the clinical data of electrocardiography (ECG),
      echocardiogram, and angiography was conducted in 271 cases of STEMI treated in
      our hospital. Of these patients 31 were treated by primary percutaneous coronary
      intervention (PCI), and 44 by intravenous thrombolysis with urokinase, including
      26 with thrombolytic treatment with concomitant PCI and 18 with rescue PCI.
      RESULTS: The patients receiving primary PCI, thrombolytic therapy along with PCI,
      and rescue PCI did not exhibit significant differences in age, sex, diabetes,
      hypertension, hyperlipidemia, smoking status, symptom onset to treatment time, or
      collateral circulation (P>0.05). The incidence of cardiac events including
      unstable angina, complex ventricular arrhythmia, and cardiac insufficiency were
      not significantly different between the 3 groups (P>0.05), nor was Killip class,
      number of Q waves on ECG, wall motion score, left ventricular ejection fraction,
      cardiac index, or stroke volume index (P>0.05). CONCLUSION: Combination of
      thrombolytic therapy and interventional therapy can be a safe and effective
      treatment of STEMI, and rescue PCI may benefit the improvement of the left
      ventricular function.

PMID- 16109572
TI  - [Modified procedure for prolapse and hemorrhoids to prevent and treat
      postoperative complications].
AB  - OBJECTIVE: To investigate the complications of procedure for prolapse and
      hemorrhoids (PPH) and their management. METHOD: The clinical data of 147 cases of
      severe hemorrhoids treated by modified PPH were analyzed in view of the operation
      method and postoperative complications. RESULT: All the prolapsed hemorrhoids
      recovered immediately after the operation. The main complications on the first
      postoperative day were abdominal distention caused by dysuria, pain, and constant
      sense of defecation urgency, which lasted for 1 to 16 days. Thirty-six cases had
      intermittent hemafecia 1 to 12 days after operation, improved with expectant
      treatment. No stoma stenosis, copracrasia or relapse of prolapse occurred during
      the follow-up for 1 to 37 months. CONCLUSION: All postoperative complications can
      be prevented, alleviated and cured with modified PPH.

PMID- 16109571
TI  - [Expressions of hypoxia inducible factor-1alpha and vascular endothelial growth
      factor in human renal cell carcinoma].
AB  - OBJECTIVE: To explore the expression of hypoxia inducible factor-1alpha (HIF
      1alpha) and vascular endothelial growth factor (VEGF) in renal cell carcinoma
      (RCC) and their relationship. METHODS: The expression of HIF-1alphaand VEGF was
      examined in 42 patients with renal cell carcinoma by SABC methods of
      immunohistochemistry. RESULTS: The positivity rate of HIF-1alpha was 57.1% in the
      RCC tissues, and there was no expression in the tissue adjacent to the tumor and
      normal tissues. The positivity rate of VEGF was 61.9% in the tumor tissues, with
      significant difference from the control tissues (P<0.05). The expression levels
      of HIF-1alpha and VEGF were significantly higher in metastatic RCC than in non
      metastatic RCC (P<0.01) tissues, and there was a significant correlation between
      HIF-1alpha and VEGF expressions (Kappa=0.41, P<0.01). CONCLUSIONS: HIF-1alpha is
      highly expressed in renal cell carcinoma tissues in close correlation with VEGF.
      HIF-1alpha and VEGF may serve as important indicators to evaluate the biological
      behaviors of RCC such as metastasis and prognosis. HIF-1alpha is an important
      regulator of VEGF.

PMID- 16109573
TI  - [Experimental study of the characteristics of renal blood flow with contrast
      ultrasound].
AB  - OBJECTIVE: To study the characteristics of renal blood flow with contrast
      ultrasound. METHODS: The examination of the renal ultrasonography was performed
      in 10 dogs after intravenous injection of Quanfuxian (a contrast agent consisting
      of C3F8 microbubbles). RESULTS: Contrast visualization appeared in the renal
      cortex and then in the outer to inner medulla at the baseline level after
      administration of the contrast agent. Notable differences in the values of
      microvascular volume (A, which was 120.3 in the corted vs 110.8 in the medulla,
      P>0.05), microcirculatory flow velocity (beta, which was 1.39 in the corted vs
      0.54 in the medulla, P<0.05), and microcirculatory flow rate (A x beta, 167.4 in
      the corted vs 59.5 in the medulla, P<0.05) were found between the corted and the
      medulla, with also marked difference between the the corted-to-the medulla ratios
      of beta and A (0.612 vs 0.078, P<0.05). CONCLUSION: Contrast ultrasound of the
      kidney provides a useful means of renal circulatory flow study.

PMID- 16109574
TI  - [Comparison of esomeprazole- and omeprazole-based triple therapy regimens for
      duodenal ulcer with Helicobacter pylori infection].
AB  - OBJECTIVE: To investigate the effect of esomeprazole- and omeprazole-based triple
      therapy regimens in the treatment of duodenal ulcer with Helicobacter pylori (Hp)
      infection. METHODS: Totally 104 patients with duodenal ulcer and Hp infection
      were randomly divided into group A (52 cases) treated with esomeprazole (20 mg),
      amoxicillin (1000 mg) and clarithromycin (500 mg) twice daily and group B (52
      cases) treated with omeprazole (20 mg), amoxicillin (1000 mg) and clarithromycin
      (500 mg) twice daily. The treatment lasted for 7 days, after which abdominal pain
      relief rate, ulcer healing rate and eradication rate of Hp as well as adverse
      effects of the medication were evaluated and compared. RESULTS: On the first and
      second days of medication, the abdominal pain relief rates were 34.6% and 59.6%
      respectively in group A, significantly higher than those in group B (17.3% and
      38.5%, respectively, P<0.05). Ulcer healing rate and Hp eradication rate were
      92.3% and 88.5 % in group A, and 88.5% and 82.7% in group B, showing no
      significant differences between the two groups (P>0.05). The adverse effects of
      the medication were rare in both groups without significant differences.
      CONCLUSION: Esomeprazole-based triple therapy may effectively eradicate Hp
      infection and promote duodenal ulcer healing with good tolerance, capable of
      achieving more speedy pain relief than omeprazole-based therapy.

PMID- 16109575
TI  - [Cytomegalovirus infection accompanied with acute pancreatitis after kidney
      transplantation].
AB  - OBJECTIVE: To explore the prevention and management of human cytomegalovirus
      (HCMV) infection accompanied with acute pancreatitis after kidney
      transplantation. METHODS AND RESULTS: A retrospective analysis of 5 patients with
      acute pancreatitis after kidney transplantation was conducted. The incidence of
      acute pancreatitis after kidney transplantation was 2.3% (5/217). All the 5 cases
      were complicated by active HCMV infection, 3 of which had hyperlipemia and 2 had
      liver dysfunction. Three cases were finally cured while the other 2 died, one of
      which was due to respiration failure arising from HCMV interstitial pneumonia
      accompanied with hemorrhagic necrotizing pancreatitis, and the other due to
      fulminating liver function failure because of active HCMV infection accompanied
      with hemorrhagic necrotizing pancreatitis. CONCLUSION: Active HCMV infection is
      the most important factor responsible for acute pancreatitis, and early diagnosis
      and treatment are crucial to lower mortality rate.

PMID- 16109576
TI  - [Management of thyroid disease-induced tracheostenosis].
AB  - OBJECTIVE: To investigate the special clinical characteristics of thyroid disease
      induced tracheostenosis and elaborate on its clinical management. METHODS: A
      retrospective analysis of 10 cases of thyroid disease-induced tracheostenosis was
      performed by reviewing the clinical record of their misdiagnoses and diagnostic
      approaches with fiberoptic bronchoscopy and/or cervical CT, thyroid scanning and
      pathological examination. The management included resection of the thyroid gland
      and airway reconstruction. RESULTS: Of the 10 patients, 3 were misdiagnosed to
      have bronchial asthma and 2 had a misdiagnosis of acute heart failure.
      Compression-induced tracheostenosis of grade II or III was identified by
      fiberoptic bronchoscopy or cervical CT, and the diagnosis of thyroid gland
      disease was established after pathological examination. Severe dyspnea was
      relieved in all patients after thyroid gland resection and airway reconstruction.
      Expandable metal stent placement was the most effective therapy for
      tracheostenosis induced by nodular goiter. Patients with tracheostomy cannula
      placement were at high risk of severe infection. CONCLUSIONS: Thyroid disease
      induced tracheostenosis is likely to be misdiagnosed, which is not difficult to
      prevent with constant awareness of the possibility. Severe dyspnea in these
      patients can be relieved effectively after thyroid gland resection and airway
      reconstruction, and the prognosis depends on the type of the thyroid disease,
      degree of the tracheostenosis and management approaches.

PMID- 16109577
TI  - [Effects of functional electric stimulation on shoulder subluxation and upper
      limb motor function recovery of patients with hemiplegia resulting from stroke].
AB  - OBJECTIVE: To observe the effects of functional electric stimulation (FES) on
      shoulder subluxation and motor function recovery of the upper extremities of
      patients with hemiplegia resulting from stroke. METHODS: Forty-eight hemiplegic
      patients were randomly divided into two groups for treatment with FES and
      shoulder pads, respectively. The recovery of the patient's shoulder subluxation
      and movement function of upper extremities were evaluated 6 weeks after treatment
      and the effects of two therapies were compared. RESULTS: The shoulder subluxation
      and movement function of the upper extremities were improved after treatment with
      both therapies (P<0.01, and FES showed better effect (P<0.01). CONCLUSIONS: FES
      can improve shoulder subluxation and motor function of the upper extremities
      affected by hemiplegia resulting from stroke.

PMID- 16109578
TI  - [Effect of etomidate on hemodynamics in elderly and shock patients during general
      anesthesia induction].
AB  - OBJECTIVE: To investigate the effect of etomidate on the hemodynamics in elderly
      and shock patients during general anesthesia induction. METHODS: Totally 100
      elderly patients or patients with hemorrhagic shock (ASA II -III ) undergoing
      surgery were studied. Anesthesia was induced with 4 microg/kg of fentanyl, 0.1
      mg/kg of vecuronium and 0.2-0.3 mg/kg of etomidate, and the mean arterial blood
      pressure (MAP), heart rate (HR), stroke volume (SV), stroke index (SI), cardiac
      output (CO), cardiac index (CI), cardiac acceleration index (ACI), left cardiac
      work (LCW), and left cardiac work index (LCWI) were recorded using thoracic
      electrical bioimpedance (TEB) hemodynamic monitoring system before induction and
      at 1, 2 and 3 min after etomidate injection as well as at 3 min after intubation.
      RESULTS: After etomidate injection, MAP, HR, SV, SI, CO, CI, ACI, LCW and LCWI
      were decreased significantly as compared with those before induction (P<0.05).
      MAP, HR, CO, CI and ACI at 3 min after intubation were higher than those before
      induction (P<0.05), and the other indices resumed the baseline level. The
      amplitudes of such changes in the recorded indices was below 20% of the baseline
      level in the course of anesthesia induction. CONCLUSION: Cardiovascular
      hemodynamics may vary slightly during the course of induction with etomidate,
      which is an ideal drug for anesthesia induction for elderly or shock patients
      with unstable hemodynamics.

PMID- 16109579
TI  - [Neuroendoscopic surgery for symptomatic septum pellucidum cyst: report of 10
      cases].
AB  - OBJECTIVE: To discuss the diagnosis, surgical indication, endoscopic fenestration
      procedures, and prognosis of symptomatic septum pellucidum cyst. METHOD: Ten
      patients with symptomatic septum pellucidum cyst showing clinical symptoms of
      elevated intracranial pressure and epilepsy with the maximal cyst width ranging
      from 12 to 35 mm underwent endoscopic cystoventriculostomy. RESULTS: During the
      follow-up period, 8 patients were symptom-free, one had significant improvement
      of the symptoms, but one failed to respond to the treatment. CONCLUSION:
      Endoscopic cystoventriculostomy is effective in the treatment of symptomatic
      septum pellucidum cyst, but care must be taken to avoid collateral injury in the
      operation.

PMID- 16109580
TI  - [Observation of short- and mid-term clinical outcome of percutaneous coronary
      intervention for acute myocardial infarction with heart failure or cardiogenic
      shock].
AB  - OBJECTIVE: To observe the short- and mid-term effects of percutaneous coronary
      intervention (PCI) in patients with ST-segment elevation acute myocardial
      infarction (AMI) complicated by heart failure and/or cardiogenic shock . METHODS:
      Altogether 90 patients with AMI were recruited, of whom 58 were treated by PCI,
      20 by thrombolytic therapy, and the other received general treatment without
      reperfusion therapy. The length of hospital stay, major adverse cardiac events
      (MACE) and left ventricular ejection fraction (LVEF) were compared between PCI
      and thrombolysis groups. The relationship between the patency time of the infarct
      related artery (IRA), thrombolysis in myocardial infarction (TIMI) grade after
      PCI and prognosis were analyzed in PCI group. RESULTS: The patency rate of IRA
      was significantly improved in patients receiving PCI therapy in comparison by
      those with thrombolytic therapy (98.3% vs 65.0%, P<0.01), and the LVEF was also
      higher in PCI group with lower mortality (6.9% vs 25.0%, P<0.05) during in
      hospital and follow-up period. CONCLUSION: PCI can be a more effective therapy
      than thrombolytic therapy in the treatment of ST-segment elevation AMI
      accompanied with heart failure and/or cardiogenic shock.

PMID- 16109581
TI  - [Expression of matrix metalloproteinase-9 and tumor necrosis factor-alpha in the
      placenta of patients with pregnancy-induced hypertension].
AB  - OBJECTIVE: To investigate the role of matrix metalloproteinase-9 (MMP-9) and
      tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of pregnancy-induced
      hypertension (PIH). METHODS: The placenta samples were collected from 57 patients
      with PIH and 24 normal pregnant women. Immunohistochemical staining was used to
      examine positive expression of MMP-9 and TNF-alpha in these samples. RESULTS: The
      positive expression of MMP-9 in the normal group was significantly higher than
      that in patients with moderate or severe PIH (P<0.01), while no significant
      difference was found between normal pregnant women and patients with mild PIH
      (P>0.05), and expression decreased drastically with the progression of PIH
      (P<0.05). The expression of TNF-alpha in the patients with mild, moderate and
      severe PIH groups were significantly higher than that in the normal group
      (P<0.05, P<0.01 and P<0.01, respectively), and the differences were also
      significant between the PIH groups of different severities (P<0.01). No
      correlation was found between MMP-9 and TNF-alpha expressions in the normal and
      mild PIH groups (r=0.287, P>0.05; r=0.382, P>0.05), in the patients with moderate
      and severe PIH, MMP-9 expression showed inverse correlation with TNF-alpha
      expression (r=-0.563, P<0.05; r=-0.681, P<0.01). CONCLUSION: Lowerd MMP-9
      expression in syncytiotrophoblast might result in defective nidation in the
      placenta where local ischemia and hypoxia cause abnormal TNF-alpha elevation,
      which might be one of the important factors inducing PIH.

PMID- 16109582
TI  - [Study of high-risk factors of surgical site infection after cesarean section].
AB  - OBJECTIVE: To study the high-risk factors of surgical site infection after
      cesarean section. METHODS: We retrospectively reviewed cesarean section cases
      with surgical site infection and evaluated the high-risk factors related to the
      infection. RESULTS AND CONCLUSIONS: Totally 14 factors were identified as the
      high-risk factors such as obesity, inadequate antibiotic prophylaxis, low
      ferrohemoglobin level, existing infection before hospitalization, multiple
      vaginal and anal examinations, premature rupture of membranes, and prolonged
      operative time. The 7 factors such as emergency operation were not shown to be
      significant high-risk factors. The probability of parturient with frequently
      vaginal examination to acquire infection following cesarean section was 75.2%,
      which was judged by classification analysis. A stepwise addition of the factors
      for analysis showed some difference in the predicted probability, which was 75.2%
      for inadequate antibiotic prophylaxis, 82.4% for low ferrohemoglobin level, 81.7%
      for prolonged operative time, 86.3% for obesity, 83.7% for premature rupture of
      the membranes, and 84.9% for existing infection before hospitalization.

PMID- 16109583
TI  - How does bupropion work as a smoking cessation aid?
AB  - Bupropion exhibits reasonable efficacy as a smoking cessation aid, yet its
      precise mechanisms of action remain unclear. This review evaluates the mechanism
      of action of bupropion by considering the clinical evidence in combination with
      results from pre-clinical experiments in vivo and in vitro. Bupropion is a weak
      inhibitor of dopamine and noradrenaline reuptake, and has also been shown to
      antagonise nicotinic acetylcholine receptor function. It is extensively
      metabolized in humans, its major metabolites reaching levels higher than those of
      bupropion itself. These metabolites share many of the pharmacological properties
      of bupropion, so they may play an important role in its clinical activity, yet
      they have been neglected in investigations into bupropion action. This review led
      to several conclusions: (1) the principal mode of bupropion action is upon the
      withdrawal symptoms following smoking cessation; (2) during withdrawal, bupropion
      may attenuate symptoms by mimicking nicotinic effects on dopamine and
      noradrenaline; (3) its ability to antagonize nicotinic receptors may prevent
      relapse by attenuating the reinforcing properties of nicotine, but probably
      cannot acutely reduce smoking; and (4) further exploration of bupropion
      metabolites and its role in withdrawal and relapse, within more appropriate
      animal models, could be crucial in the determination of the precise mechanisms by
      which bupropion exerts its activity in smoking cessation. Greater elucidation of
      the exact mechanisms of action of bupropion could lead to the development of new
      drugs even more beneficial in promoting smoking abstinence.

PMID- 16109584
TI  - The acute anti-craving effect of acamprosate in alcohol-preferring rats is
      associated with modulation of the mesolimbic dopamine system.
AB  - Acamprosate (Campral) is a drug used clinically for the treatment of alcoholism.
      In order to examine further the time-course and mechanism of action of
      acamprosate, the effect of acute and repeated acamprosate administration was
      examined on (i) operant ethanol self-administration and (ii) voluntary home cage
      ethanol consumption by alcohol-preferring Fawn-Hooded, iP and Alko Alcohol (AA)
      rats. Acutely, acamprosate was shown to cause a significant decrease in operant
      ethanol self-administration by Fawn-Hooded and alcohol-preferring iP rats in part
      by decreasing the motivational relevance of a specific ethanol cue; however,
      repeated injection of acamprosate led to tolerance to this effect. Voluntary
      alcohol consumption in the home cage in Fawn-Hooded and AA rats was also reduced
      by an acute acamprosate injection; however, again tolerance developed to repeated
      injections. In a separate experiment, the effect of acamprosate on markers of the
      dopaminergic system was examined. Interestingly, acute acamprosate was also shown
      to cause increased dopamine transporter density and decreased dopamine D2-like
      receptor density within the nucleus accumbens but not in the caudate-putamen,
      suggesting a link between the decreased motivational salience of the ethanol cue
      and altered dopaminergic signalling within the nucleus accumbens. With repeated
      injections of acamprosate, markers of the dopaminergic system returned to steady
      state levels with a similar temporal profile to the development of tolerance in
      the behavioural studies. Along with previous studies, our findings indicate that
      acamprosate modulates the mesolimbic dopaminergic system and may thereby decrease
      ethanol reinforcement processes; however, these effects undergo tolerance in
      alcohol-preferring rats and may in part explain the fact why some subjects are
      non-responders to chronic acamprosate treatment.

PMID- 16109585
TI  - Effects of MPEP on expression of food-, MDMA- or amphetamine-conditioned place
      preference in rats.
AB  - Recent studies have revealed the effectiveness of 2-methyl-6
      (phenylethynyl)pyridine (MPEP), a highly selective antagonist of metabotropic
      glutamate receptors subtype 5 (mGluR5), in conditioned drug reward. In a previous
      study we showed that MPEP blocks expression of context-conditioned morphine- but
      not cocaine reward in the rat. The present study now examines the effectiveness
      of MPEP in the expression of context-conditioned food, MDMA ('ecstasy') or
      amphetamine reward. Therefore, three groups of rats were conditioned either to
      food, MDMA or amphetamine in the conditioned place preference (CPP) paradigm.
      After conditioning, CPP expression and locomotion were determined simultaneously
      in the presence and absence of the respective reward (i.e. food or drug), or
      after application of 50 mg/kg MPEP (the dose that was most effective in reducing
      morphine CPP expression in our previous study). As a result, MPEP reduced
      locomotion in all groups. Furthermore, only expression of amphetamine CPP was
      inhibited by MPEP, while expression of food and MDMA CPP was not affected,
      suggesting that the MPEP-induced inhibition of amphetamine CPP expression was not
      causally linked to the reduction of locomotion. Overall, we conclude that MPEP
      reduces expression of context-conditioned amphetamine but not MDMA or food
      reward.

PMID- 16109586
TI  - Exposure to chronic stress increases the locomotor response to cocaine and the
      basal levels of corticosterone in adolescent rats.
AB  - Repeated exposure to stress results in augmentation in the locomotor response to
      psychostimulant drugs. We investigated the locomotor response to a novel
      environment or cocaine [10 mg/kg, intraperitoneally (i.p.)] and basal
      corticosterone levels in male adolescent rats exposed to chronic restraint or
      variable stress. Animals in the chronic restraint group were restrained for 1
      hour daily. The chronic variable stress protocol consisted of exposure to
      different stressors twice a day in random order. Chronic restraint and variable
      stress regimens began simultaneously on postnatal day (P) 25 and were applied for
      10 days. During this period the control group was left undisturbed except for
      cleaning the cages. Three days after the last exposure to stress, cocaine- and
      novelty-induced locomotion were recorded in an activity cage. Plasma
      corticosterone levels were determined in a subset of stress and control animals.
      Exposure to both chronic restraint and variable stress increased cocaine-induced
      locomotion and basal corticosterone plasma levels, while no change was observed
      in the response to a novel environment. Moreover, rats exposed to variable stress
      displayed the greatest locomotor response following a challenge dose with cocaine
      when compared to control and chronic restraint stress groups. This observation
      indicates that the stress regimen is relevant to the degree of stress-induced
      sensitization to cocaine.

PMID- 16109587
TI  - Effects of acute administration of methamphetamine on Narp mRNA in rat brain.
AB  - Narp (neuronal activity-regulated pentraxin) is a secreted immediate early gene
      product functioning as a cluster factor for the AMPA receptor subtype of
      glutamate receptors. This study was designed to examine the effects of acute
      administration of methamphetamine (MAP) on the Narp gene in rat brain using
      reverse transcription - polymerase chain reaction (RT-PCR). Acute administration
      of MAP [4.6 mg/kg, intraperitoneally (i.p.)] increased Narp mRNA in the
      prefrontal cortex, whereas the same treatment with MAP decreased Narp mRNA in the
      hippocampus. Therefore, Narp gene could be involved in the MAP-induced effects.

PMID- 16109588
TI  - Polymorphism in the serotonin transporter gene and response to treatment in
      African American cocaine and alcohol-abusing individuals.
AB  - The serotonin transporter (5-HTT) regulates serotonin transmission and modulates
      behavioral effects of drug of abuse. A polymorphism in the promoter region of the
      serotonin transporter gene (5-HTTLPR) yielding a short (S) and long (L) allele
      has been associated with severity of substance abuse. The aims of the study were
      to investigate whether 5-HTTLPR genotypes differed in their response to treatment
      in cocaine- and alcohol-abusing patients. Polymerase chain reaction-based
      genotyping of a 44 base pair insertion/deletion polymorphism was performed in 141
      African American cocaine-dependent patients with concurrent alcohol use who were
      entering a 12-week behaviorally oriented outpatient treatment program. In
      treatment, end of treatment and 6-month follow-up outcome measures included
      changes in Addiction Severity Index (ASI) scores, urine drug screens, days in
      treatment, individual/group sessions, dropout and completion rates. As expected,
      there was a reduction in substance abuse by the end of treatment and follow-up (F
      = 5.15, p = 0.000). However, there were no differences in the reduction in
      cocaine use across the LL, LS and SS genotypes. Interestingly, individuals with
      the S allele showed greater severity of alcohol use at admission (F = 4.84, p =
      0.03), and the SS genotype showed less improvement in alcohol measures than the
      LL at follow-up (F = 3.68, p = 0.03), after controlling for baseline variables.
      While we found no association of the 5-HTTLPR variants with severity of cocaine
      abuse or any cocaine-related outcome measures, the data suggested that the 5
      HTTLPR polymorphism may distinguish responders from non-responders to behavioral
      treatment in terms of alcohol use. Further investigations are required to
      determine the role of the 5-HTTLPR polymorphism in influencing treatment -
      outcome among substance abusers.

PMID- 16109589
TI  - Tryptophan hydroxylase gene 1 polymorphisms are not associated with suicide
      attempts in alcohol-dependent individuals.
AB  - A serotonergic dysfunction was suggested to be involved into the biological
      susceptibility of suicidal behaviour. Tryptophan hydroxylase (TPH), the rate
      limiting enzyme in serotonin biosynthesis, is a significant regulating factor in
      the serotonergic system. Recently the A-6526G, and G-5806T and A-779C
      polymorphisms of the TPH 1 gene were identified and suggested to be associated
      with suicidal behaviour, but study results are conflicting. We examined a
      possible association of the A-6526G, and G-5806T and A-779C polymorphisms with
      suicide attempts in a sample of 80 alcohol-dependent individuals with a history
      of at least one suicide attempt. This group was analysed in comparison with 241
      alcohol-dependent subjects without such a history. No significant relationship
      between haplotype and genotype distribution and allele frequencies of these
      polymorphisms with suicide attempts were detected. Furthermore, no association
      with number of suicide attempts and TPH haplotypes were found. Our data do not
      support the hypothesis of A-6526G, G-5806T or A-779C polymorphisms to be
      associated with suicide attempts in alcohol-dependent individuals.

PMID- 16109590
TI  - Allelic association of a dopamine transporter gene polymorphism with antisocial
      behaviour in heroin-dependent patients.
AB  - Polymorphism of a variable number of tandem repeats (VNTR) in the 3' untranslated
      region of exon 15 of the SLC6A3 gene, coding for the dopamine transporter (DAT),
      was analysed to test whether length variation contributes to differences in the
      individual susceptibility to aggressive - criminal behaviour and liability to
      heroin dependence. The repeat number of the DAT polymorphism was assessed in 125
      healthy subjects and 104 heroin-dependent subjects (including 52 addicted
      individuals with violent behaviour and criminal records). There was no
      significant difference in the frequencies of genotypes and alleles between heroin
      dependent subjects and control subjects. On the contrary, there was a significant
      difference between offenders and non-offenders, p = 0.004 and p = 0.002,
      respectively, among heroin-dependent subjects. No association was found between
      DAT polymorphism and history of suicide. Buss - Durkee Hostility Inventory (BDHI)
      mean total scores were significantly higher in heroin addicts than in controls (p
      < 0.001) and in antisocial - violent heroin addicts in comparison with addicted
      individuals without antisocial behaviour (p < 0.005). The regression analysis of
      BDHI subscales, performed to provide an estimate of the magnitude of any
      potential effect on the risk of aggressiveness associated with the variants in
      DAT VNTR, showed that the presence of the 9 - 9 genotype significantly increases
      the risk of irritability and direct aggressiveness more than six and 10 times
      with respect to the 9 - 10 genotype. Our findings suggest that the 9-repeat
      allele of the DAT polymorphism confers increased susceptibility to antisocial -
      violent behaviour and aggressiveness, rather than drug dependence per se in
      heroin-dependent males.

PMID- 16109591
TI  - Oxcarbazepine versus carbamazepine in the treatment of alcohol withdrawal.
AB  - In a single-blinded and randomized pilot study efficacy and tolerability of
      oxcarbazepine versus carbamazepine were investigated in 29 patients during
      therapy of alcohol withdrawal. No initial differences were found regarding
      sociodemographic data and alcohol-related parameters, indicating successful
      randomization. The oxcarbazepine group showed a significant decrease of
      withdrawal symptoms and reported significantly less 'craving for alcohol'
      compared to the carbamazepine group. Subjectively experienced side effects,
      normalization of vegetative parameters and improvement in the cognitive
      processing speed did not reveal differences for both groups. Therefore,
      oxcarbazepine might be an interesting alternative to carbamazepine, and having
      almost no addictive potential, no clinically relevant interaction with alcohol
      and no prominent sedatory effect, possibly also to other drugs such as
      benzodiazepines or clomethiazole, in the treatment of alcohol withdrawal
      syndrome.

PMID- 16109592
TI  - A double-blind, placebo-controlled study of naltrexone in the treatment of
      alcohol dependence in Taiwan.
AB  - The aim of this study was to investigate the effectiveness of naltrexone in
      Taiwanese Han males with alcohol dependence. In conjunction with limited
      supportive psychotherapy, 40 alcoholic patients, who met Diagnostic and
      Statistical Manual version III revised (DSM-III-R) criteria for alcohol
      dependence, were assigned to a randomized double-blind, placebo-controlled trial
      of naltrexone hydrochloride (50 mg/day) for 14 weeks following alcohol
      detoxification. Among recruited patients, 45% (n = 9/20) of the naltrexone
      treated subjects and 35% (n = 7/20) of the placebo-treated subjects dropped out
      (p = 0.374). The relapse rates between the two groups were not significant (p =
      0.671). Subjects taking naltrexone reported less alcohol craving compared with
      placebo-treated subjects. In support of previous reports, the present results
      suggest that naltrexone may be safe and effective in craving reduction in alcohol
      dependent subjects.

PMID- 16109593
TI  - Neuroimaging studies of brain corpus striatum changes among heroin-dependent
      patients treated with herbal medicine, U'finer capsule.
AB  - Chronic exposure to heroin is associated with structural changes in dopaminergic
      (DA) neurones. The present study examined the effects of a new herbal medicine,
      U'finer capsule, on the brain corpus striatum and DA systems, comparing pre- and
      post- treatment in 36 heroin-dependent patients. Neuroimaging studies were
      performed by using single photon emission computed tomography (SPECT) with 99mTc
      TRODAT-1 as radiotracer. The results show that U'finer significantly repaired the
      damaged bilateral corpus striatum, restoring it to a 'panda eye' shape, analogous
      in size and shape to that of the healthy volunteers. DA transporter (DAT)
      function in the bilateral corpus striatum was restored to a normal state after
      recovery from neurotoxic insult. These findings suggest that U'finer is a
      reliable herbal medicine in the treatment of heroin dependency.

PMID- 16109594
TI  - Successful pregnancy outcome in a patient with primary Addison's disease.
AB  - A 32-year-old primigravida with primary Addison's disease was followed up from
      the early stages of pregnancy to delivery and puerperium by a multidisciplinary
      medical board. Besides fetal surveillance, great attention was given to steroid
      replacement therapy in order to avoid complications. Vaginal labor resulted in
      the birth of a healthy neonate that performed well.

PMID- 16109595
TI  - Is there any correlation between stages of endometriosis and severity of chronic
      pelvic pain? Possibilities of treatment.
AB  - We report herein findings on 181 patients, suffering from pelvic endometriosis
      confirmed by histology, whose main symptom was chronic pelvic pain (CPP). They
      attended the outpatient clinic at the 1st Department of Obstetrics and
      Gynaecology, Semmelweis University in Budapest, between 1 January 1995 and 1
      January 2000. The extent of pelvic endometriosis was determined on the basis of
      the 1985 revised scoring system of the American Fertility Society (R-AFS). The
      short form of the McGill pain questionnaire was used for the evaluation of CPP.
      After the first operative intervention, therapy with a gonadotropin-releasing
      hormone (GnRH) analog was given for 6 months. Second-look laparoscopy was
      performed 8-10 weeks after the end of GnRH-analog treatment, which was followed
      by a non-conventionally administered, monophasic oral contraceptive (OC)
      treatment. In the long term, 118 patients received the non-conventionally
      administered, monophasic OC treatment, which contained a third-generation
      progestogen, to be taken continuously for at least 6 months. The other 63
      patients who did not receive OC treatment for one reason or another were
      evaluated as a control group. We analyzed data on CPP before the first surgical
      intervention, then following therapy with the GnRH analog at the second-look
      operation, and then after 6, 12, 18 and 24 months. We also reviewed potential
      causes of CPP, especially focused on endometriosis. No correlation was found
      between the stage of endometriosis according to R-AFS score and the severity of
      CPP. At the 24-month follow-up after second-look laparoscopy, the non
      conventionally administered monophasic OC treatment was found not only to
      significantly reduce pain scores, but also the required radical operative
      solution (hysterectomy plus bilateral adnexectomy) for CPP by OC users.

PMID- 16109596
TI  - A study to look at hormonal absorption of progesterone cream used in conjunction
      with transdermal estrogen.
AB  - Natural progesterone creams are gaining popularity as a possible treatment for
      menopausal symptoms, and many women may be using them with estrogen. We planned
      to evaluate, using an open plan study, the systemic absorption of a combination
      of transdermal estrogen and progesterone. Women applied transdermal progesterone
      40 mg and transdermal estrogen 1 mg daily over 48 weeks. Women were assessed at
      intervals of 12 weeks. Significant increases in plasma levels of progesterone and
      estradiol were seen after 12 weeks, although only low plasma progesterone levels
      were found (median 2.5 nmol/l) and no further increase was noted over the
      remainder of the study period. A significant correlation was found between plasma
      levels of the two hormone (r = 0.315, p = 0.045). Women reported significant
      reductions in menopausal symptoms, as measured by the Green Climacteric Scale,
      after 24 and 48 weeks of combined treatment. There may be similar mechanisms of
      absorption of the two hormones, although the doses used in our study produced sub
      luteal levels of progesterone. There was no evidence of accumulation of
      progesterone with time, and further study is needed to assess the efficacy and
      safety of this combination of hormones.

PMID- 16109597
TI  - Matrix metalloproteinase-13 and membrane type-1 matrix metalloproteinase in
      peritoneal fluid of women with endometriosis.
AB  - OBJECTIVE: It is becoming more and more evident that different types of matrix
      metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in the
      pathogenesis of endometriosis. The aim of the present study was to measure levels
      of the active forms of MMP-13 and membrane type-1 matrix metalloproteinase (MT1
      MMP)/MMP-14 as well as TIMP-2 in the peritoneal fluid of women with
      endometriosis. STUDY DESIGN: We determined the levels of the active forms MMP-13
      and MT1-MMP/MMP-14 as well as TIMP-2 in the peritoneal fluid of 20 women with
      endometriosis and 18 controls by different types of enzyme-linked immunosorbent
      assay. RESULTS: We found that the concentrations (mean +/- standard deviation) of
      total active MMP-13 and endogenous active MT1-MMP/MMP-14 in the peritoneal fluid
      of patients with endometriosis were 1.69 +/- 0.67 and 3.12 +/- 1.07 ng/ml,
      respectively. In control women the corresponding values were 3.02 +/- 0.43 and
      4.45 +/- 1.03 ng/ml. The differences were statistically significant (p < 0.0001
      and p < 0.0004 for MMP-13 and MMP-14, respectively). Levels of TIMP-2 did not
      differ significantly. CONCLUSIONS: Decreased concentrations of active MMP-13 and
      MT1-MMP/MMP-14 may imply that the proteolytic activity of the peritoneal milieu
      of women with endometriosis is disturbed, which may have implications in the
      pathogenesis of the disease.

PMID- 16109598
TI  - Expression of matrix metalloproteinase-3 in mouse endometrial stromal cells
      during early pregnancy: regulation by interleukin-1alpha and tenascin-C.
AB  - During the peri-implantation period, the endometrium undergoes tissue remodeling
      and cellular rearrangement. To clarify the involvement of matrix
      metalloproteinases (MMPs) in endometrial remodeling, we isolated total RNAs from
      the endometrium of non-pregnant and pregnant mice on days 3 to 5 and evaluated
      mRNA expression of MMP-2, -3, -9, -11 and -13 using reverse transcription
      polymerase chain reaction (PCR). Prompt increases in MMP-3 and -13 mRNA were
      found on day 4 of pregnancy. Quantitative real-time PCR showed that expression of
      MMP-3 and -13 increased significantly on day 4, up to 8.4 +/- 2.7 times and 3.4
      +/- 1.5 times, respectively, the level in non-pregnant endometrium (p < 0.05). On
      day 4, immunohistochemistry demonstrated MMP-3-positive endometrial stromal
      cells. At the same time, tenascin-C (TN-C) mRNA increased 11.1 +/- 4.0 times from
      the level in non-pregnant endometrium (p < 0.004). To clarify regulation of MMP-3
      expression, we examined the effects of interleukin-1alpha (IL-1alpha) and TN-C on
      MMP-3 mRNA in cultured mouse endometrial stromal cells. Both substances resulted
      in a dose-dependent increase in MMP-3 mRNA (6.1 +/- 1.8-fold at 1 ng/ml of IL
      1alpha and 3.9 +/- 1.8-fold at 10 mug/ml of TN-C). This study shows that MMP-3
      expression is upregulated in endometrial stromal cells of the peri-implantation
      period and may be controlled by IL-1alpha and TN-C.

PMID- 16109599
TI  - Different routes of progesterone administration and polycystic ovary syndrome: a
      review of the literature.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disorder in woman of
      reproductive age. Although extensive studies have been performed in past decades
      to investigate the pathobiological mechanisms underlying the unset of this
      disease, its etiology remains unknown. Progesterone is a hormone of paramount
      importance in ovulation, implantation and luteal phase support. Low levels of
      progesterone have been found in the early luteal phase in PCOS patients.
      Granulosa cells from polycystic ovaries show an altered progesterone production.
      Moreover, the lack of cyclical exposure to progesterone may have a role in the
      development of the gonadotropin and androgen abnormalities found in PCOS
      patients. Ovulation failure and progesterone deficiency may facilitate the
      hypothalamic-pituitary abnormalities causing the associated disordered
      luteinizing hormone secretion in PCOS. Progesterone may be administered to PCOS
      patients in the following cases: to induce withdrawal bleeding, to suppress
      secretion of luteinizing hormone, in ovulation induction in clomiphene citrate
      resistant patients and in luteal phase support in assisted reproduction. We
      discuss the pharmacologic characteristics of the different routes of progesterone
      administration with reference to these diverse indications, the therapeutic
      objectives and patient compliance.

PMID- 16109600
TI  - Effectiveness of sodium benzoate as a freshwater low toxicity antifoulant when
      dispersed in solution and entrapped in silicone coatings.
AB  - The traditional solution for preventing organisms from attaching to submerged
      surfaces is to apply antifouling coatings or biocides. Based on the varied
      defence mechanisms exhibited by biofilms, the antifoulant needs to prevent
      bacterial attachment during the early stages of biofilm formation. The potential
      of benzoic acid and sodium benzoate (NaB) as antifoulants for deterring
      freshwater bacterial attachment was evaluated with the antifoulants dispersed in
      solution or entrapped in silicone coatings. Effectiveness was based on the
      decrease in microbial attachment, limited toxicity, and minimum alteration of the
      properties of the coatings. The optimal NaB concentration when dispersed in
      solution, 700 mg l-1, resulted in a biofilm surface coverage of only 3.34% after
      four weeks. The model silicone, Sylgard 184, demonstrated a better overall
      performance than the commercial coating, RTV11. Sylgard 184 containing sodium
      benzoate had 41-52% less biofilm in comparison to the control Sylgard 184,
      whereas both the control and NaB-entrapped RTV11 coatings had significant biofilm
      coverage.

PMID- 16109601
TI  - Graft-vs-host disease after non-myeloablative hematopoietic cell transplantation.
AB  - Non-myeloablative preparative regimens have reduced regimen-related toxicities
      after allogeneic hematopoietic cell transplantation (HCT), which allows for the
      treatment of patients not eligible for myeloablative HCT. The reduced non-relapse
      mortality associated with non-myeloablative HCT is in part explained by the
      decreased incidence and severity of acute graft-vs-host disease (GVHD). Compared
      with conventional HCT, the onset of acute GVHD is delayed, and some patients may
      present with signs and symptoms characteristic of acute GVHD after day 100, in
      the absence of hallmarks of chronic GVHD. In contrast to the overall negative
      impact of acute GVHD on outcome, the net effects of chronic GVHD after non
      myeloablative HCT appear to be beneficial, translating into improved progression
      free survival among patients with different hematological malignancies. One
      obvious explanation for this beneficial effect is the strong association between
      chronic GVHD and protection against recurrent malignancy (graft-vs-tumor effect).
      Future strategies are aimed at reducing the risk of acute GVHD, in particular
      "early-onset" GVHD (before day 50), which is associated with increased non
      relapse mortality and decreased overall survival, and at decreasing the
      corticosteroid dependence among patients who require immunosuppressive treatment
      for clinically established GVHD.

PMID- 16109602
TI  - Importance of plasma matrix metalloproteinases (MMP) and tissue inhibitors of
      metalloproteinase (TIMP) in development of fibrosis in agnogenic myeloid
      metaplasia.
AB  - Tissue inhibitors of metalloproteinase (TIMP) and matrix metalloproteinases (MMP)
      are key elements in the formation, remodeling and degradation of matrix protein.
      Bone marrow fibrosis in AMM, with deposition, not only of interstitial and
      basement membrane collagen but also of fibronectin, vitronectin, laminin and
      proteoglycans, results from a disturbed balance between synthesis and proteolytic
      degradation of matrix protein. Although TIMP and MMP play important roles in the
      development of fibrosing diseases of skin, liver and lung, only a few studies of
      TIMP and MMP in the formation of bone marrow fibrosis in AMM have been published.
      The literature shows that TIMP-1 (both the total, complex and the free form) is
      significantly increased in AMM and other myeloproliferative syndromes (including
      polycythemia vera (PV) and essential thrombocytosis (ET)), while MMP-3 is
      significantly decreased, and levels of MMP-2 and MMP-9 are not different from
      control values. Variance from control values for both TIMP-1 and MMP-3 is more
      evident in AMM than in PV and ET, thus further suggesting bone marrow fibrosis in
      AMM results from enhanced TIMP and decreased MMP activities.

PMID- 16109603
TI  - Clinical implications of blast immunophenotypes in myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are malignant disorders of hematopoietic cells.
      For many neoplasms, immunophenotype data of the neoplastic cells provide valuable
      information in clinical practice. However, the clinical values of immunophenotype
      data have not yet been firmly established for MDS. Since MDS blasts are not
      predominant in the bone marrow and peripheral blood, which makes reliable
      immunophenotyping of blasts difficult, we used a newly developed density
      centrifugation reagent to generate blast-enriched MDS samples for phenotyping.
      The key findings of our study, which phenotyped blasts from 116 patients with MDS
      or acute leukemia transformed from MDS, were the following. (1) MDS blasts were
      usually CD34( + )CD38( + )HLA-DR( + )CD13( + )CD33( + )CD2(-)CD3(-)CD5(-)CD8(
      )CD19(-)CD20(-) in flow cytometric analysis and often lacked myeloperoxidase in
      cytochemistry, regardless of the MDS subtype. (2) MDS blasts showed asynchronous
      expression of antigens (expression of both stem cell antigens and antigens of
      mature myeloid cells). (3) During disease progression of MDS, phenotypic clonal
      evolution (transition from blasts with a relatively mature phenotype to blasts
      with a more immature phenotype) occurred in at least some cases. (4) CD7
      positivity was an independent variable associated with a short survival in MDS.
      Further studies of blast immunophenotypes will deepen our understanding of MDS
      and hopefully improve the clinical approach to these intractable disorders.

PMID- 16109604
TI  - Cyclin D expression in chronic lymphocytic leukemia.
AB  - Although the majority of circulating leukemic cells in chronic lymphocytic
      leukemia (CLL) are in G0/early G1, recent studies have shown that these cells
      have undergone multiple cell divisions. In this study, we have determined whether
      there are abnormalities in cell cycle control in CLL by examining the three
      cyclin D isoforms in 43 patients and correlating the findings with clinical
      features. Cyclin D mRNA was measured by a sensitive RNase protection assay and
      the order of expression in CLL cells was D3 > D2 > D1. The mean cyclin D1 and D3
      mRNA levels were 4 to 6-fold higher in CLL cells than in normal peripheral blood
      B cells. In contrast, the levels of cyclin D2 mRNA were similar in CLL and normal
      B cells. Expression of the cyclin D isoforms was two- to four-fold greater in
      normal T cells than B cells, and the order of expression for both cell types was
      D2 > D3 > D1. The relative overexpressions of cyclins D1 and D3 in CLL were
      unrelated to gene amplification, as assessed by Southern blotting, but structural
      changes in the genes were seen in four patients. Both cyclin D1 and D3 mRNA
      levels correlated positively with lymphocyte doubling time (LDT) and inversely
      with Rai stage and duration of disease. In addition, a significant correlation
      was observed between cyclin D mRNA levels and survival, with patients having high
      levels of cyclin D1, and to a lesser extent cyclin D3, mRNA having the best
      survival. Thus, cyclin D1 and D3 are relatively overexpressed in CLL cells and
      patients with higher levels have low stage disease, long LDT and prolonged
      survival. Further studies should evaluate the predictive value of cyclin D
      measurements in comparison to other prognostic markers in CLL.

PMID- 16109605
TI  - The effect of absolute lymphocyte count recovery kinetics on survival after
      autologous stem cell transplantation for non-Hodgkin's lymphoma.
AB  - Absolute lymphocyte count (ALC) >or=500 cells/microl at day 15 after autologous
      stem cell transplantation (ASCT) is a powerful independent, prognostic indicator
      for survival in multiple hematological malignancies. A limitation in these
      studies was the selection of a single time point (day 15 post-ASCT) as the only
      discriminator of clinical outcome in relation to ALC recovery. We hypothesized
      there is a continuous and not discrete relationship between ALC recovery and
      clinical outcome post-ASCT in NHL. Therefore, we analyzed 274 consecutive
      patients who underwent ASCT for NHL between 1987 and 2001. The primary end point
      was to assess the impact of the kinetics of post-ASCT lymphocyte recovery>or=500
      cells/microl (K-ALC) on overall survival (OS) and progression-free survival
      (PFS). K-ALC was a predictor of OS and PFS when the Cox proportional hazards
      model was used with K-ALC entered as a continuous variable (p<0.0001).
      Multivariate analysis demonstrated K-ALC recovery post-ASCT to be an independent
      prognostic indicator for OS and PFS. These data support our hypothesis that the K
      ALC post-ASCT is associated with clinical outcome in NHL.

PMID- 16109606
TI  - Proliferation rate and outcome in children with T-cell rich B-cell lymphoma: a
      clinicopathologic study from the NHL-BFM-study group.
AB  - T-cell rich B-cell lymphoma (TCRBCL) is considered a rare variant of aggressive B
      cell lymphoma characterized by few neoplastic cells and a large reactive
      infiltrate with striking similarities to nodular lymphocyte predominant Hodgkin's
      lymphoma (NLPHL). In childhood, these tumors occur even less frequently. Biopsy
      specimens at diagnosis from 16 children (13 boys) with a median age of 12 years
      (range, 7 to 18) were immunophenotyped. The proliferation rate was assessed with
      monoclonal antibodies against Ki-67 and repp86 antigens and additional clonality
      analyses were performed. Ten patients had localized disease and only two had B
      symptoms. All patients showed high Ki-67 expression (median: 80%, range 40% to
      90%), but low repp86 expression (median: 25%, range 10% to 50%). PCR-based
      clonality studies of the hypervariable CDR III region of the immunoglobuline
      heavy chain and the T-cell receptor gamma-chain genes demonstrated predominant
      clones in nine and five patients, respectively. Three patients had previous or
      concomitant NLPHL and two of them received initial treatment for Hodgkin's
      disease. All patients achieved remission after a brief polychemotherapy regimen.
      Two patients subsequently relapsed and one was rescued by salvage therapy
      including autologous stem cell transplantation. At a median follow-up of 23
      months, 15 patients (94%) are alive. The striking contrast between the
      proliferation rates determined by Ki-67 and repp86 expression points to a
      possible arrest in the G1 cell cycle phase because repp86 expression is
      restricted to the S, G2 and M cell cycle phases. This G1 arrest may explain the
      paradoxon of high Ki-67 expression in a paucicellular lymphoma with a favorable
      prognosis in young patients.

PMID- 16109607
TI  - The prognostic value of the expression of Bcl-2, p53 and LMP-1 in patients with
      Hodgkin's lymphoma.
AB  - This study was undertaken to evaluate the clinical significance of the expression
      of Bcl-2, p53 and LMP-1 in Hodgkin and Reed - Sternberg cells of patients with
      Hodgkin's lymphoma. The expression of these proteins in pre-treatment tissue
      biopsy specimens was correlated with presenting clinical features, failure-free
      survival (FFS) and overall survival (OS) in 83 patients with a confirmed
      Hodgkin's lymphoma treated in a single institution. HIV-positive patients were
      excluded. Patients were classified according to the International Prognostic
      Score (IPS) in low-risk (0 - 2 factors) and high-risk groups. The median age was
      41 years (15 - 84), 41% were women, and 93% had advanced-stage disease (IIB -
      IVB). The expression of Bcl-2, p53 and LMP-1 was not associated with the complete
      remission rate, FFS or OS. The IPS risk group was the only factor significantly
      associated with OS. Patients with a high IPS had a lower 5 year OS (43% vs. 79%,
      P = 0.003). The expression of Bcl-2, p53 and LMP-1 did not add prognostic
      information to the IPS.

PMID- 16109608
TI  - TNF family molecules in the serum of patients with B-cell chronic lymphocytic
      leukemia (B-CLL).
AB  - Tumor necrosis factor (TNF) superfamily, involving membrane receptors and ligands
      are important for the growth and survival of leukemic B cells. In the present
      study levels of TNF-alpha, sTNFRp55, sTNFRp75 and sCD40 and sCD40L in the serum
      of patients with B-CLL before and after treatment were measured. In sera of
      patients before treatment increased concentrations of sCD40 and decreased
      concentrations of sCD40L were shown. Increased concentrations of TNF-alpha and
      sTNFRp75 and lack of changes in sTNFRp55 concentrations were also found. Results
      obtained suggest that the relationships between examined soluble form of TNF
      family proteins may influence the development of B-cell chronic lymphocytic
      leukemia. The used therapy with 2CdA and CMC led to a favorable effect for host
      through changes in the relations between sCD40 and sCD40L. It was also found that
      sCD40 and sCD40L serum concentrations, which are dependent on the clinical stage
      and used therapy, are more sensitive tumor markers than TNF-alpha and its soluble
      receptor in patients with B-CLL treated with 2CdA and CMC.

PMID- 16109609
TI  - Gemcitabine-induced pericardial effusion and tamponade after unblocked cardiac
      irradiation.
AB  - Gemcitabine therapy has been associated with radiation recall reactions when used
      in the treatment of carcinoma. We report four cases of hemodynamically
      significant pericardial effusion in patients with refractory lymphoma who were
      receiving gemcitabine, all of whom had a history of mediastinal radiation without
      subcarinal blocking. All four patients had pericardial abnormalities on
      echocardiography prior to receiving gemcitabine. Two patients required emergent
      surgical procedures. Of twenty other patients in our practice who received
      gemcitabine for refractory lymphoma without developing pericardial effusion, none
      had received prior direct radiation to the heart. The overall response rate of
      these 24 refractory lymphomas to gemcitabine-containing regimens was 46%.
      Although gemcitabine-based regimens have clear efficacy in refractory lymphoma,
      prior mediastinal radiation without subcarinal blocking may be a relative
      contraindication, especially in the presence of pericardial abnormalities on
      echocardiography. Physicians should be aware of the potential for developing a
      gemcitabine-induced radiation recall reaction resulting in hemodynamically
      significant pericardial effusion.

PMID- 16109610
TI  - Primary breast lymphoma: outcome of 7 patients and a review of the literature.
AB  - Primary breast lymphomas (PBL) are uncommon neoplasms. Seven PBL were diagnosed
      between March 1993 and October 2002. A lumpectomy (n=4) or radical mastectomy
      (n=3) was performed; 5 patients were in clinical stage (CS) II and 2 in CS IV; 6
      patients received the CEOP regimen (cyclophosphamide, vincristine, epirubicin and
      prednisone) after surgery and 4 also had additional radiotherapy; 1 patient did
      not receive any treatment after local excision. Five patients (71%) achieved
      complete remission and 2 (29%) partial remission, with an overall response rate
      of 100%. All remitter patients are alive and well after a median follow-up of 75
      months (range 10--121 months). Two patients in partial remission died of
      progressive disease. After a median follow-up of 99 months (range 84--111 months)
      for surviving patients, the 10 year overall and disease-free survival rates are
      both 71%, with 5 patients well and still free of disease. We conclude that the
      optimal sequence of full-dose anthracycline-containing regimens and radiation
      therapy should be the treatment of choice for patients with PBL.

PMID- 16109611
TI  - Management of gastric lymphoma with chemotherapy alone.
AB  - PURPOSE: The optimal therapy for gastric lymphoma except MALToma has not yet been
      established. This study was undertaken to investigate whether gastric lymphoma
      can be managed effectively and safely with chemotherapy alone. PATIENTS AND
      METHODS: A total of 58 patients (median age 56 years) with newly diagnosed
      gastric lymphoma between 1989--2001 at Seoul National University Hospital and who
      were initially managed with chemotherapy alone were evaluated. MALToma was
      excluded from the pathologic review. RESULTS: All patients received initially
      anthracycline-containing chemotherapy. ECOG performance scale 0--1 was 88% and B
      symptoms were present in 41.4%. Diffuse large B cell type was the most common
      (74.1%). Stage IE, II1E accounted for 51.7% and II2E, IIIE, IV for 48.3%. The
      international prognostic index (IPI) of risk was low in 39.7%, low-intermediate
      in 22.4%, high-intermediate in 15.5% and high in 22.4%. The complete response
      rate after first-line chemotherapy was 71.4% and the partial response rate was
      12.2%. (overall response rate: 83.6%). Among patients who did not reach the
      complete response, a further complete response was achieved by second-line
      chemotherapy including etoposide-based regimen. Ultimately, the maximum complete
      response rate by chemotherapy was 83.7% (92% in stage IE, II1E, 75% in stage
      II2E, IIIE, IV). Median overall survival was 47.4 months (84.7 months in stage
      IE, II1E, 32.5 months in stage II2E, IIIE, IV) and the 5-year survival rate was
      46%. Bleeding as a complication occurred in 3 of 58 patients (5.6%) and these
      cases were controlled by embolization or conservative management. No perforation
      episode occurred and surgical intervention due to complication was not necessary.
      Organ preservation was possible in 57 of 58 patients (98%). The one gastrectomy
      was performed due to a partial clinical response to chemotherapy but the specimen
      showed pathologic CR. Multivariate analysis revealed that only IPI had a
      significant influence on survival. CONCLUSIONS: Gastric lymphoma except MALToma
      can be managed effectively and safely with chemotherapy alone.

PMID- 16109612
TI  - Primary gastric lymphoma in Jordan with special emphasis on descriptive
      epidemiology.
AB  - The aim of this study was to examine the clinicopathological features and
      epidemiology of primary gastric lymphoma in Jordan as a model for Middle East
      countries where such data is scarce. From 1991--2002, 219 patients with primary
      gastric malignancy were managed at our hospitals. Among these there were 19
      patients with primary gastric lymphoma. Pertinent data for these patients were
      analyzed. Primary gastric lymphoma constituted 65.5% of all gastrointestinal
      lymphoma and 8.7% of all gastric malignancies. Male-to-female ratio was 2.8:1.
      The mean age was 56 years (range 39--82). The incidence was 0.6/100,000. The
      proximal third was the most common localisation. Abdominal pain was the commonest
      presentation. Low-grade MALT lymphomas, high-grade MALT lymphomas, diffuse large
      cell B lymphomas and T cell lymphoma were found in 21.1, 26.3, 47.4 and 5.3%,
      respectively. Nine patients had gastrectomy followed by chemotherapy, 6 patients
      had palliative resection, 3 patients had chemotherapy only and the remaining
      patient was treated with Helicobacter pylori eradication. The mean follow-up for
      all patients was 42.2 months. The 5-year survival rates for stages IE (n=5), IIE
      (n=4), IIIE (n=6) and IVE (n=4) were 100, 67, 27 and 0%, respectively (p=0.0003).
      The overall 5 years survival was 48.2%. Primary gastric lymphoma in Jordan shares
      some epidemiological features with western disease. Jordanian patients are
      detected and treated after a relatively long delay. Advanced stage at diagnosis
      correlated with poor outcome. There is a need of an earlier diagnosis and
      subsequent better care.

PMID- 16109613
TI  - Endothelial precursors and mature endothelial cells are increased in the
      peripheral blood of myelodysplastic syndromes.
AB  - Increased angiogenesis has been demonstrated to be a significant prognostic
      factor in many solid tumors. In the oncohematological setting, it has been
      associated with myelodysplastic syndromes (MDS), chronic myeloid leukemia, acute
      lymphoid, and myeloid leukemias. Recently, increased circulating endothelial
      cells (CECs) have been associated with breast cancer and non-Hodgkin lymphoma
      (NHL). Based on these premises we analysed total and activated CECs, and
      endothelial precursors (CEPs) in 50 MDS patients and 20 healthy donors. CECs and
      CEPs were quantified by flow cytometry. CEC levels were compared with bone marrow
      (BM) microvessel density (MVD). In addition, some angiogenic factors, namely
      vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)
      and soluble VEGF-Receptor2 (VEGFR2), were tested in the sera from 25 MDS
      patients. Total, activated CECs and CEPs were significantly increased in MDS when
      compared to control group (p<0.0001); whereas in the MDS cases no association was
      found with French--American--British (FAB), International Prognostic Scoring
      System (IPSS) subtypes or survival. Patients with higher CECs also showed higher
      MVD. Among the cytokines analysed, sVEGFR2 was significantly higher in the lower
      IPSS risk classes, while the levels of bFGF directly correlated with total and
      activated CECs. Taken together these data strengthen the hypothesis of a possible
      role of angiogenesis in MDS pathogenesis.

PMID- 16109614
TI  - Erythroid cells in suppressing leukemia cell growth.
AB  - This paper indicates that murine nucleated erythroid cells (EC) are able to
      reduce, in a dose-dependent manner, the proliferation of both L1210 lymphoma and
      P815 mastocytoma cells and that the leukemia cell growth inhibitory activity of
      unseparated bone marrow (BM) cells may be markedly augmented by their short-term
      culturing with erythropoietin (Epo). These results raise the intriguing
      possibility to utilize erythropoesis-stimulating, therapeutic strategies with the
      purpose of inhibiting leukemia cell growth in the body.

PMID- 16109615
TI  - Are MTT assays the right tool to analyze drug resistance caused by ABC
      transporters in patient samples?
AB  - Drug resistance can be caused by ATP-binding-cassette (ABC)-transporters which
      function as outward pumps for chemotherapeutic drugs. The aim of the present
      study was to analyze the association between eight ABC-transporters (BCRP, MDR1,
      SMRP, MRP1, MRP2, MRP3, MRP4, and MRP5) and in vitro drug resistance. Leukemic
      cells from 52 children with previously untreated acute leukemia (ALL: n=37; AML:
      n=15) were analysed. The expression of the ABC-transporters was measured by
      TaqMan real-time PCR. In vitro drug resistance to cytarabine, vincristine,
      tioguanine, daunorubicin, etoposide, dexamethasone, and prednisone was analysed
      with methyl-thiazol-tetrazolium (MTT) assays.MDR1 was weakly associated with
      resistance to vincristine (p<0.05) in AML samples. No other correlation between
      an ABC-transporter and a higher in vitro drug resistance was found. In vitro drug
      resistance was not associated with the simultaneous expression of a larger number
      of ABC-transporters.MTT assays are a widely used and validated method to analyse
      in vitro drug resistance but they may not be a useful tool to detect resistance
      which is caused by drug efflux in patient samples. If that is the case, MTT
      assays and the expression of ABC-transporters could provide complementary
      information on the drug resistance profile of patients with acute leukemia.

PMID- 16109616
TI  - Regression of advanced non-splenic marginal zone lymphoma after treatment of
      hepatitis C virus infection.
AB  - We describe a patient with chronic hepatitis C virus (HCV) infection who
      presented with extranodal (right salivary gland and bone marrow) marginal zone
      lymphoma of mucosa-associated lymphoid tissue (MALT). Within a year, the lymphoma
      progressed to involve peripheral lymph nodes and the liver. After treatment of
      HCV with peginterferon and ribavirin, he achieved complete radiographic response
      and remains in remission two years later. This is an example of a patient in whom
      treatment of HCV infection led to regression of non-splenic, extranodal marginal
      zone lymphoma. It suggests that HCV testing and treatment should be considered in
      all patients with marginal zone lymphomas, including non-splenic types.

PMID- 16109617
TI  - An unusual case of indolent B-cell lymphoma with distinct chronic lymphocytic
      leukemia and marginal zone differentiation according to the site of involvement.
AB  - The immunological profile of lymphoproliferative disorders is usually conserved
      whatever the involved site, thus allowing a reliable diagnosis from peripheral
      blood analysis, especially in small lymphocytic lymphoma/chronic lymphocytic
      lymphoma (SLL/CLL). Here we present a case wherein the cytology and
      immunophenotype of blood specimen and bone marrow argue in favor of SLL/CLL with
      a typical Matutes score (5/5), whereas the cyto-histology and immunophenotype of
      spleen specimen led to the diagnosis of splenic marginal zone B-cell lymphoma
      (SMZL). Moreover genomic analysis showed that the splenic cells displayed a SMZL
      signature. Whereas these data suggested the presence of 2 B-cell clones, the
      study of the mutational status of IgVH gene in blood and spleen demonstrated the
      presence of a single clone, which likely developed simultaneously along two
      distinct ways of differentiation according to the anatomic site suggesting here
      the predominant role of a micro-environmental factor in cell differentiation.
      Although rare, this kind of event must be kept in mind as a cause of
      discrepancies between diagnoses from different sites.

PMID- 16109618
TI  - E6a2 BCR-ABL fusion with BCR exon 5-deleted transcript in a Philadelphia positive
      CML responsive to Imatinib.
AB  - Chronic myeloid leukemia (CML) is characterized in 90% of patients by the
      presence of the reciprocal translocation t(9;22)(q34;q11) leading to the fusion
      of the BCR and ABL genes. Most patients with Philadelphia chromosome positive CML
      express either the e13a2 (b2a2) or e14a2 (b3a2) MBCR-ABL mRNA. Some variant cases
      have been reported expressing the fusion e1a2 (mBCR-ABL) or e19a2 (microBCR-ABL).
      Very rare atypical transcripts such as e13a3, e14a3 or e6a2 have been described.
      We report here a sixth case of a Ph positive patient with an e6a2 BCR-ABL fusion
      transcript and describe for the first time a chimeric molecule alternatively
      spliced for exon 5 of the BCR gene.

PMID- 16109619
TI  - Very good partial response in a patient with MALT-lymphoma of the lung after
      treatment with low-dose thalidomide.
AB  - Pulmonary MALT lymphoma is a rare disease entity and generally follows an
      indolent clinical course. Due to scarce information from randomized prospective
      trials, no standardized therapy protocols exist. Besides irradiation and
      chemotherapy, novel biological agents such as the anti CD20-antibody rituximab
      and thalidomide constitute a promising new approach. In this report we
      demonstrate the case of a 52-year-old male patient with extra-intestinal MALT
      lymphoma of the lung. After 10 months of treatment with low dose thalidomide
      (100mg/d), very good partial response of the intrapulmonary lesions was achieved.

PMID- 16109620
TI  - Regression of pulmonary MALT lymphoma after treatment with rituximab.
AB  - We describe a patient with extranodal (pulmonary) marginal zone B-cell lymphoma
      of mucosa-associated lymphoid tissue (MALT) who was refractory to treatment with
      cytotoxic chemotherapy. After a single four-week course of rituximab she had
      significant regression of pulmonary lesions and remains progression free 19
      months after finishing her treatment. This case report demonstrates the potential
      efficacy of rituximab as a single therapeutic agent in patients with pulmonary
      MALT lymphoma.

PMID- 16109621
TI  - Miscibility behavior and formation mechanism of stabilized felodipine
      polyvinylpyrrolidone amorphous solid dispersions.
AB  - In the present study, solid dispersion systems of felodipine (FEL) with
      polyvinylpyrrolidone (PVP) were developed, in order to enhance solid state
      stability and release kinetics. The prepared systems were characterized by using
      Differential Scanning Calorimetry, X-Ray Diffraction, and Scanning Electron
      Microscopy techniques, while the interactions which take place were identified by
      using Fourier Transformation-Infrared Spectroscopy. Due to the formation of
      hydrogen bonds between the carbonyl group of PVP and the amino groups of FEL,
      transition of FEL from crystalline to amorphous state was achieved. The
      dispersion of FEL was found to be in nano-scale particle sizes and dependent on
      the FEL/PVP ratio. This modification leads to partial miscibility of the two
      components, as it was verified by DSC and optimal glass dispersion of FEL into
      the polymer matrix since no crystalline structure was detected with XRD. The
      above deformation has a significant effect on the dissolution enhancement and the
      release kinetics of FEL, as it causes the pattern to change from linear to
      logarithmic. An impressive optimization of the dissolution profile is observed
      corresponding to a rapid release of FEL in the system containing 10% w/w of FEL,
      releasing 100% in approximately 20 min. The particle size of dispersed FEL into
      PVP matrix could be classified as the main parameter affecting dissolution
      optimization. The mechanism of such enhancement consists of the lower energy
      required for the dissolution due to the amorphous transition and the fine
      dispersion, which leads to an optimal contact surface of the drug substance with
      the dissolution media. The prepared systems are stable during storage at 40 +/- 1
      degrees C and relative humidity of 75 +/- 5%. Addition of sodium docusate as
      surfactant does not affect the release kinetics, but only the initial burst due
      to its effect on the surface tension and wettability of the systems.

PMID- 16109622
TI  - Development of novel interpenetrating network gellan gum-poly(vinyl alcohol)
      hydrogel microspheres for the controlled release of carvedilol.
AB  - Novel interpenetrating polymeric network microspheres of gellan gum and
      poly(vinyl alcohol) were prepared by the emulsion cross-linking method.
      Carvedilol, an antihypertensive drug, was successfully loaded into these
      microspheres prepared by changing the experimental variables such as ratio of
      gellan gum:poly(vinyl alcohol) and extent of cross-linking in order to optimize
      the process variables on drug encapsulation efficiency, release rates, size, and
      morphology of the microspheres. Formation of interpenetrating network and the
      chemical stability of carvedilol after preparing the microspheres was confirmed
      by Fourier transform infrared spectroscopy. Differential scanning calorimetry and
      x-ray diffraction studies were made on the drug-loaded microspheres to
      investigate the crystalline nature of the drug after encapsulation. Results
      indicated a crystalline dispersion of carvedilol in the polymer matrix. Scanning
      electron microscopy confirmed the spherical nature and smooth surface morphology
      of the microspheres produced. Mean particle size of the microspheres as measured
      by laser light scattering technique ranged between 230 and 346 microm. Carvedilol
      was successfully encapsulated up to 87% in the polymeric matrices. In vitro
      release studies were performed in the simulated gastric fluid or simulated
      intestinal fluid. The release of carvedilol was continued up to 12 h. Dynamic
      swelling studies were performed in the simulated gastric fluid or simulated
      intestinal fluid, and diffusion coefficients were calculated by considering the
      spherical geometry of the matrices. The release data were fitted to an empirical
      relation to estimate the transport parameters. The mechanical properties of
      interpenetrating polymeric networks prepared were investigated. Network
      parameters such as molar mass between cross-links and cross-linking density for
      interpenetrating polymeric networks were calculated.

PMID- 16109623
TI  - Evaluation of the transdermal permeation behavior of Proterguride from drug in
      adhesive matrix patches through hairless mouse skin.
AB  - The transdermal in vitro permeation behavior of the highly potent dopamine
      agonist Proterguride was investigated using hairless mouse skin as a model
      membrane. Drug in adhesive matrix formulations based on different types of
      pressure-sensitive adhesives (Eudragit E 100 and Gelva7883 as acrylates, Oppanol
      B 15 SFN as polyisobutylene, and BioPSA 7-4202 as silicone) with a drug load of
      3% by weight were manufactured. All patches were examined for drug
      crystallization by polarized microscopy immediately after the manufacturing
      process and after storage for 30 days in sealed aluminium laminate bags at
      ambient temperature and at 40 degrees C, respectively. Furthermore, the influence
      of the drug load in acrylate-based formulations onto the steady-state flux of
      Proterguride was examined. The Eudragit E 100 system delivered a significantly
      higher steady-state flux than the systems based on Oppanol B 15 SFN and also a
      somewhat higher steady-state flux than the Gelva-based patch. An addition of 10%
      by weight of the crystallization inhibitor povidone 25 did not significantly
      influence the steady-state flux of Proterguride from acrylate matrices. The
      lipophilic silicone and polyisobutylene adhesives facilitated drug
      crystallization within the short storage periods at both conditions, probably due
      to the absence of povidone 25, which was incompatible with these polymers.
      Varying the drug load in acrylate-based formulations led to a linear increase of
      the steady-state flux until the steady-state flux of Proterguride leveled off and
      the patches tended to drug crystallization. It was found that Gelva-based patches
      show good physical stability, good skin adhesion, and moderate flux values and,
      thus, can be evaluated as a basis for a suitable formulation for the transdermal
      administration of Proterguride.

PMID- 16109624
TI  - The effect of selected water-soluble excipients on the dissolution of paracetamol
      and Ibuprofen.
AB  - The purpose of this investigation was to study the dissolution behavior of
      paracetamol and ibuprofen in the presence of a range of selected potential
      excipients. First, a pH-solubility profile was generated for both drugs, and the
      effect of changing hydrodynamic conditions on the intrinsic dissolution rate was
      investigated. It was established that both drugs dissolved according to the
      diffusion-layer model. Paracetamol solubility (approximately 20.3 mg mL(-1)) did
      not vary from pH 1.2-8.0, corresponding to the in vivo range in the
      gastrointestinal tract. Ibuprofen had an intrinsic solubility of approximately
      0.06 mg mL(-1), and pK(a) was calculated as 4.4. Second, the effects of selected
      potential excipients (lactose, potassium bicarbonate, sodium bicarbonate, sodium
      chloride, and tartaric acid) were evaluated by measuring the effect of the
      inclusion of each additive in the dissolution medium on drug solubility, drug
      intrinsic dissolution rate, and solution viscosity. The results were evaluated
      using the diffusion-layer model, and it was determined that for paracetamol, the
      collected data fitted the model for all the excipients studied. For ibuprofen, it
      was found that there were differences between the excipients that raised the
      solution pH above the pK(a) to those that did not. For the excipients raising the
      pH above the pK(a), the effect on intrinsic dissolution rate was not as high as
      that expected from the change in drug solubility. It was postulated that this
      might be due to lack of penetration of the excipient into the drug boundary layer
      microenvironment. Formulators may calculate the effect of adding an excipient
      based on solubility increases but may not find the dissolution rate improvement
      expected.

PMID- 16109625
TI  - Interest of multifunctional lipid excipients: case of Gelucire 44/14.
AB  - This paper focuses on the interest of a multifunctional lipid excipient from the
      lauroyl macrogolglycerides, i.e., Gelucire 44/14. This compound, characterized by
      a drop point of 44 degrees C and a HLB (Hydrophilic Lipophilic Balance) of 14, is
      made of a specific mixture, leading to particular properties. Gelucire 44/14
      forms a fine emulsion in contact with aqueous fluids, inducing a pseudo
      solubilization of poorly water-soluble active substances and thus increasing
      their bioavailability. It could be used either as a binder for immediate release
      pellets by melt granulation or as a self-emulsifying drug delivery system by
      capsule molding or as a powder obtained by cryogenic grinding. These different
      methods and their interests are then discussed.

PMID- 16109626
TI  - Effect of the drug-excipient ratio in matrix-type-controlled release systems:
      computer simulation study.
AB  - The main objective of this work is to study the drug release behavior from inert
      matrix systems by using computer simulation. This study allowed us to propose a
      new statistical method to evaluate the drug percolation threshold as a function
      of the exposed surface area of the device. The matrix system was simulated as a
      simple cubic lattice. The sites of the lattice were randomly occupied at various
      drug-excipient ratios. By simulating a diffusive process, the drug was delivered
      from the matrix system. The obtained release profiles were fitted to two
      different models: near the excipient percolation threshold, the square root of
      the time was well fitted, whereas close to (but above) the drug percolation
      threshold, the power law described accurately the release data. A relationship
      between the initial drug load and the amount of drug trapped inside the matrix
      system at infinite time was found. This relationship was conveniently described
      by an error function. Percolation thresholds in the matrix systems were
      determined from the latter relationship by using a nonlinear regression method.
      The assessment of percolation thresholds depends on the exposed surface area of
      the matrix systems. Moreover, estimated percolation thresholds were in agreement
      with the predicted values stated in the percolation theory.

PMID- 16109627
TI  - Protein binding characteristics of 2'-benzoyloxycinnamaldehyde.
AB  - The protein binding characteristic of 2'-Benzoyloxycinnamaldehyde (BCA) was
      investigated, which has demonstrated a potent antitumor effect against several
      human solid tumor cell lines and in human tumor xenograft nude mice. Protein
      binding of BCA in human serum was 86 +/- 0.91% and the predominant binding
      protein of BCA was fatty-acid-free human serum albumin (HSA) (81 +/- 0.91%). The
      binding of BCA to HSA was outlined by one class, and Ka and n of BCA were 1.65 x
      10(5) M(- 1) and 0.374, respectively. Displacement studies with fluorescence
      probes suggested that BCA mainly binds to site I on HSA, and BCA-induced
      enhancement in site II binding. The limited drug-drug interaction experiments
      suggested that BCA influences both site I and site II drug-HSA bindings via
      different mechanisms; a competitive displacement and a probable allosteric
      conformational change in HSA, respectively.

PMID- 16109628
TI  - Preparation and pharmacokinetic evaluation of Tashinone IIA solid lipid
      nanoparticles.
AB  - Tashinone IIA loaded solid lipid nanoparticles (TA-SLN) coated with poloxamer 188
      was prepared by emulsification/evaporation. The TA-SLN was characterized by
      transmission electron microscope and dynamic light scattering (DLS). The results
      showed that the TA-SLN had an average diameter of 98.7 nm with a zeta potential
      of - 31.6 mv and the drug loading of 4.6% and entrapment efficiency of 87.7%. In
      vitro release experiment showed that the release of Tashinone IIA from TA-SLN was
      in accordance with the Weibull equation. The best model fitting experimental data
      was a two-compartment open model with first-order. The area under curve of plasma
      concentration-time (AUC) and mean residence time (MRT) of TA-SLN were much higher
      than those of Tashinone IIA control solution (TA-SOL). The results of
      pharmacokinetic studies in rabbits indicated that the formulation of TA-SLN was
      successful in providing a delivery of slow release of Tashinone IIA.

PMID- 16109629
TI  - Controlled drug delivery systems based on thiolated chitosan microspheres.
AB  - The aim of the present study was to verify the potential of chitosan-thio-butyl
      amidine (TBA) microspheres as carrier systems for controlled drug delivery. In
      this study microspheres were prepared utilizing water in oil (w/o) emulsification
      solvent evaporation technique. A concentration of 0.5% of chitosan-TBA conjugate
      displaying 100 microM thiol groups per gram polymer was used in the aqueous phase
      of the emulsion in order to prepare microspheres. The obtained non-aggregated
      free-flowing microspheres were examined with conventional light microscope as
      well as scanning electron microscopy (SEM). The microscopic images indicated that
      the prepared chitosan-TBA microspheres were of spherical shape and smooth surface
      while microparticles obtained from the unmodified chitosan were of porous
      structure and non-spherical shape. Particle size distribution was determined to
      be in the range from 1 to 59 microm. The free thiol group content of chitosan-TBA
      microspheres prepared with an aqueous phase of pH 2, 5, and 6.5 were determined
      to be 71.4, 49.4, and 8.2 microM/g polymer, respectively. Furthermore, results
      attained from in vitro release studies with fluorescein isothiocyanate labelled
      dextran (FITC-dextran) loaded chitosan-TBA microspheres showed a controlled
      release rate for more than three hours while the control reached the maximum peak
      level of release already within an hour. According to these results, chitosan-TBA
      microspheres seem to be a promising tool in transmucosal drug delivery for poorly
      absorbed therapeutic agents.

PMID- 16109630
TI  - Inclusion complexation of lorazepam with different cyclodextrins suitable for
      parenteral use.
AB  - The development of a parenteral lorazepam formulation, using cyclodextrins (CDs)
      as inclusion complexation agents, was investigated. CDs suitable for parenteral
      injection, i.e., hydroxypropyl-beta-cyclodextrin (HP-beta-CD), hydroxypropyl
      gamma-cyclodextrin (HP-gamma-CD), sulfobutylether-7-beta-cyclodextrin (SBE-7-beta
      CD), and maltosyl-beta-cyclodextrin (malt-beta-CD) were studied for the
      possibility to increase the solubility of lorazepam. Lorazepam interacted with
      all tested CD derivatives and 1:1 complexes are formed. HP-beta-CD exerts the
      highest solubility improvement, reaching about 6 mg/ml lorazepam in 30% (w/v) CD
      solution. When using SBE-7-beta-CD or malt-beta-CD only half of that
      concentration can be dissolved. HP-gamma-CD interacts much less with lorazepam.
      Parenteral solutions with 4 mg/ml in 30% (w/v) HP-beta-CD solution, with 2 mg/ml
      in 30% (w/v) SBE-7-beta-CD, and with 2 mg/ml lorazepam in 15% (w/v) HP-beta-CD,
      were prepared. Sterile filtration of the formulation needs to be applied because
      of massive degradation of lorazepam during autoclaving. No precipitation is
      observed after dilution of the different formulations with (physiological) water
      or with 5% dextrose in water, which proves their suitability for administration
      with perfusions. The stability of the preparations was investigated in aqueous
      medium. During the first month, in all solutions more than 90% of lorazepam
      remained; after 3 months, less than 60% of lorazepam remained in the solutions
      with 15% (w/v) HP-beta-CD and around 65-70% in the solutions with 30% (w/v) of
      CDs. Because of this short stability time, the preparations need to be
      lyophilized.

PMID- 16109631
TI  - A new HPLC approach for the determination of hydrophilic and hydrophobic
      components: the case of pseudoephedrine sulfate and loratadine in tablets.
AB  - Effective isocratic separations of decongestants and antihistamines is a
      challenging analytical task due to wild differences in their lipohilicities
      (hydrophilic decongestants and hydrophobic antihistamines). In this paper a new
      approach for resolving such a problem is described taking pseudoephedrine sulfate
      and loratadine as an example. The chromatographic behavior of pseudoephedrine
      sulfate and loratadine on RP C18 and C8 columns were studied in presence and
      absence of sodium lauryl sulfate (SLS). The effect of combining two different
      types of stationary phases (cyano and C18 or C8) on the relative retention of the
      two compounds was investigated. In conclusion, it was found that the combination
      of a C18 column followed by a standard cyano column provides a stationary phase
      that separates both compounds effectively and within a reasonable time. This
      approach was compared to a literature method and demonstrated to have superior
      selectivity.

PMID- 16109632
TI  - Modification of porcine pancreatic lipase with Z-proline.
AB  - Porcine pancreatic lipase was modified with Z-proline via the constitution of
      amide bonds between the free amino groups of lipase and the carboxyl groups of Z
      proline, which were activated by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide
      (EDC). Different amounts of Z-proline were bound to lipase. Modification degree
      was determined by 2,4,6-trinitrobenzene sulphonic acid (TNBS), by means of the
      decrease in free amino groups on lipase. The reason for choosing Z-proline was
      its unique structural characteristics, protected amino groups, and its effect on
      protein conformation by reducing the flexibility of the lipase molecule, thus
      achieving stabilization against changes in pH and temperature. After the
      modification, porcine pancreatic lipase was found to have new physicochemical
      characteristics, such as optimum alkaline pH stability and thermal stability at
      elevated temperatures.

PMID- 16109633
TI  - Efficient production of recombinant aldehyde reductase and its application for
      asymmetric reduction of ethyl 4-chloro-3-oxobutanoate to ethyl (R)-4-chloro-3
      hydroxybutanoate.
AB  - An NADPH-dependent aldehyde reductase (ALR, EC1.1.1.2) gene is cloned from
      Sporobolomyces salmonicolor ZJUB 105, and inserted into plasmid pQE30 to
      construct the expression plasmid (pQE30-ALR). A variety of E. coli strains were
      employed as hosts to obtain transformants with pQE30-ALR, respectively. Among
      these different types of transformants, the highest enzyme activity of ALR can be
      produced with E. coli M15 (pQE30-ALR). The bioactivity of ALR could be further
      improved significantly by the optimization of induction conditions. The results
      showed that the enzyme activity of ALR reached 6.48 U/mg protein, which is
      fifteen times higher than that of S. salmonicolor ZJUB 105. This recombinant
      strain was applied to the asymmetric reduction of ethyl 4-chloro-3-oxobutanoate
      (COBE) to ethyl (R)-4-chloro-3- hydroxybutanoate (CHBE). The results showed that
      the yield and optical purity of (R)-CHBE reached 98.5% and 99% e.e. (enantiomeric
      excess), respectively.

PMID- 16109634
TI  - A comparative study of the metal ion uptake and antioxidant enzyme activities of
      Fusarium equiseti and Fusarium acuminatum as a function of external magnesium
      concentration.
AB  - The increase of Mg2+, from 1.3 to 3 microM, in growth medium of F. equiseti and
      F. acuminatum increased intracellular magnesium levels from 0.83 and 0.81 microM
      to 1.75 and 1.42 microM on the 12th day, respectively. Intracellular magnesium
      levels also elevated depending upon the number of incubation days. The maximum
      manganese levels of F. equiseti and F. acuminatum obtained in 1.6 microM Mg2+
      culture medium were 0.67 and 1.23 microM, while maximum iron levels were
      determined to be 1.3 microM Mg2+ as 0.51 and 0.29 microM, respectively. The
      maximum intracellular iron and manganese levels were decreased significantly with
      increasing Mg2+ concentration in the culture medium and were increased depending
      upon the incubation period. However, intracellular zinc levels of these strains
      didn't change with Mg2+ concentration and incubation period. The maximum
      superoxide dismutase (MnSOD) activities of F. equiseti and F. acuminatum, related
      to increased intracellular manganese levels up to 1.6 microM Mg2+ in growth
      medium, were determined to be 78 and 110 IU/mg, respectively. CAT activity
      variations showed agreement with SOD activity and reached a maximum at 320 and
      225 IU/mg under the same conditions. The minimum LPO levels of the Fusarium
      strains with the maximum MnSOD and CAT activities were determined as 1.2 and 0.9
      nmol MDA/g., wet weight. The higher LPO level of F. equiseti grown at the same
      condition, in spite of 1.42-fold higher CAT activity due to the 1.41-fold lower
      SOD activity, as well as a 2.0-fold higher iron level, indicated increases in the
      generation of reactive oxygen species via the Fenton reaction.

PMID- 16109635
TI  - Dimerization of ferulic and caffeic acids by purified peroxidase isolated from
      Bupleurum salicifolium callus culture.
AB  - A novel peroxidase that catalyses the transformation of caffeic acid and ferulic
      acid via oxidative coupling was purified from callus cultures of Bupleurum
      salicifolium petioles. The enzyme, which was purified over 2,900-fold, is a
      glycoprotein with a molecular weight of 38,000, determined by SDS/PAGE and gel
      filtration. The K(m) values obtained were 2.4x10(-4) M for caffeic and 2.6x10(-4)
      M for ferulic acid, while the K(m) values for H2O2 with caffeic acid was 4x10(-5)
      M and for H2O2 with ferulic acid was 4.8x10(-4) M. The purified peroxidase
      exhibits lower activity with typical peroxidase substrates (guaiacol and
      pyrogallol) than it does with caffeic and ferulic acids, but does not exhibit any
      activity with other phenylpropanoids tested (cinnamic acid, coumaric acid, and
      3,4-dimethoxycinnamic acid).

PMID- 16109636
TI  - Purification and characterization of an extracellular alpha-D-glucuronidase from
      Phlebia radiata.
AB  - Alpha-D-glucuronidase was isolated from the culture filtrate of Phlebia radiata
      grown on wheat bran and purified to homogeneity by chromatographic methods. The
      final enzymic preparation was purified 65-fold with an activity yield of 58%; it
      showed a high level of specific activity (over 23,000 nkat/mg protein). The
      molecular and hydrolytic properties of the purified enzyme were studied. The
      secreted alpha-glucuronidase had a molecular weight of 110 kDa, as established by
      gel permeation chromatography (GP HPLC), had a determined pI just below 4.4, and
      was stable at pH 5.5 for prolonged times. The carbohydrate content in protein
      molecules was found to be 15%. The activity of alpha-D-glucuronidase peaked at pH
      3,8 and 60 degrees C with aldouronic acids preparation as the substrate. The
      Michaelis-Menten constant (K(m)), the maximum reaction velocity (V(max)), and the
      activation energy (E(a)) were 0.18 mM, 0.13 microM/min and 5.91 kJ/mol,
      respectively. The alpha-glucuronidase was active mainly on small substituted
      xylooligomers. When this enzyme was used with endoxylanase for the degradation of
      oat xylan, synergistic effects were observed.

PMID- 16109637
TI  - Rapid and simple procedure for homogenizing leaf tissues suitable for mini-midi
      scale DNA extraction in rice.
AB  - We describe a rapid and simple procedure for homogenizing leaf samples suitable
      for mini/midi-scale DNA preparation in rice. The methods used tungsten carbide
      beads and general vortexer for homogenizing leaf samples. In general, two samples
      can be ground completely within 11.3+/-1.5 sec at one time. Up to 20 samples can
      be ground at a time using a vortexer attachment. The yields of the DNA ranged
      from 2.2 to 7.6 microg from 25-150 mg of young fresh leaf tissue. The quality and
      quantity of DNA was compatible for most of PCR work and RFLP analysis.

PMID- 16109640
TI  - Roles of adherence and matrix metalloproteinases in growth patterns of fungal
      pathogens in cornea.
AB  - PURPOSE: To investigate the roles of adherence and matrix metalloproteinases
      (MMPs) in growth patterns of major fungal pathogens in cornea. METHODS: Ninety
      six eyes in 96 rabbits were equally divided into four groups receiving
      inoculation of fungal conidia of Aspergillus fumigatus, Candida albicans,
      Fusarium solani, and Penicillium citreo-viride, respectively, to induce fungal
      keratitis. Corneas in each group were obtained at 2, 8, 16 hr, and 1, 2, 3, 5,
      and 8 days after inoculation and were subjected to scanning electron microscopy,
      histopathological examination, and gelatin zymography. Eight saline-inoculated
      eyes in another eight rabbits served as controls. RESULTS: All eyes in the fungus
      inoculated groups developed fungal keratitis. The binding of conidia to corneal
      epithelial basement membrane was initiated earlier in the A. fumigatus and C.
      albicans groups than in the F. solani and P. citreo-viride groups. Destruction of
      basement membrane began at 1 to 3 days. Histopathologically, infiltration of
      inflammatory cells was more evident in the A. fumigatus and C. albicans groups
      than the F. solani and P. citreo-viride groups at 3 days. The hyphae of A.
      fumigatus and C. albicans traversed the cornea in a plane perpendicular to the
      stromal lamellae, whereas the hyphae of F. solani and P. citreo-viride lay
      parallel to the corneal lamellae. MMP-9 and MMP-2 were found in all infected
      corneas. At 3 days, proteolysis was most active; the level of MMP-9 was higher in
      the A. fumigatus and C. albicans groups than in the F. solani and P. citreo
      viride groups. There were positive correlations among the number of binding
      conidia, degree of inflammation, and level of MMP-9 (p < 0.05). CONCLUSIONS: The
      adherence ability, chemotaxis to neutrophils, and MMP-9 expression level differ
      in eyes with different fungal pathogens, which may contribute to the different
      growth patterns of fungi in cornea.

PMID- 16109641
TI  - A mathematical model for tear drainage through the canaliculi.
AB  - PURPOSE: Tear drainage through the canaliculi has been extensively studied
      experimentally but there has been no attempt to develop a quantitative model for
      this process. In this paper, we develop a mathematical model for the tear
      drainage through the canaliculi. METHODS: The mathematical model is based on the
      experimental findings of Doane, according to which the muscle action during a
      blink drives the tear drainage. In this paper, mathematical models are developed
      for the tear flow and the canalicular deformation, and the model equations are
      solved to predict the tear drainage rates. RESULTS: The drainage rates depend on
      various physiological parameters. The time to attain a steady state during the
      drainage process can vary from about 0.0010 s to 0.0546 s, and the tear drainage
      rate can vary from 0.10 microl/min to 4.00 microl/min for a normal tear film, for
      physiologically reasonable values of various system parameters. CONCLUSIONS: The
      model predictions agree with various physiological experiments, at least
      qualitatively. The model also helps resolve the differences between various tear
      drainage experiments.

PMID- 16109642
TI  - Immunohistochemical analysis of orbital connective tissue specimens of patients
      with active Graves ophthalmopathy.
AB  - PURPOSE: To explore the immune mechanism of Graves ophthalmopathy (GO) by
      analyzing infiltrating cells in orbital connective tissue (OCT) specimens of
      patients with active GO using immunohistochemical methods. METHODS: Five OCT
      specimens obtained from patients with active GO and five control specimens
      obtained from forensic cadavers who died from nonmedical reasons were stained
      with anti-CD3, CD4, CD8, CD45RO, HLA-Dr, CD25, and TNF-alpha monoclonal
      antibodies. Positively stained cells were counted and results were interpreted as
      cell counts/mm2. Four of five GO patients had never been treated with any
      immunomodulating therapy. Only one had received oral prednisolone prior to tissue
      sampling, but this treatment had ceased 5 months before surgery. RESULTS: The
      retro-orbital tissue specimens obtained from forensic cadavers did not show any
      significant positive staining for any monoclonal antibody tested. However, the
      specimens from GO patients showed positively stained means of 36.66 +/- 4.61 HLA
      Dr+, 12.8 +/- 3.42 CD8+, 11.8 +/- 1.78 CD4+, 16.6 +/- 1.81 CD3+, 21.2 +/- 3.12
      CD45RO+, 10.4 +/- 2.07 TNF-alpha+, 7.2 +/- 1.48 CD25+, 3.2 +/- 1.09 CD4+CD8+, 4.6
      +/- 1.67 CD4+CD45RO+, 2.8 +/- 0.83 CD8+CD45RO+, 1.6 +/- 0.89 CD4+CD25+, and 1.8
      +/- 1 0.83 CD8+CD25+ cells/mm2. CONCLUSIONS: Our study supports that most of the
      infiltrating lymphocytic cells in the active stage of GO are T cells, and a
      significant proportion of them are CD45RO+ cells. Infiltration of OCT by HLA-Dr+,
      CD25+, and TNF-alpha cells suggests that Th1-type immune reaction with the
      interference of proinflammatory cytokine(s) (TNF-alpha) may be important in the
      pathogenesis of disease. Further studies are needed to understand the disease
      pathogenesis and may provide a scientific basis for future treatment alternatives
      for the disease (e.g., anti-cytokine treatment).

PMID- 16109643
TI  - Adhesion complex in cultivated limbal epithelium on amniotic membrane after in
      vivo transplantation.
AB  - PURPOSE: To investigate adhesion complex formation in cultivated human limbal
      epithelium after transplantation into the limbal deficient model. METHODS:
      Cultivated epithelium on amniotic membrane was transplanted into limbal deficient
      rabbits. The transplanted rabbits and the controls were sacrificed at 1, 2, 3,
      and 4 weeks. The adhesion complex was examined by electron microscopy and
      immunohistochemistry. RESULTS: Morphologically identifiable hemidesmosomes
      appeared at 1 week, and matured adhesion complex was found at 3 weeks. Collagen
      VII was partly stained after transplantation. The mean numbers of
      hemidesmosomes/2.25 microm were 2.3 +/- 0.9, 2.5 +/- 0.5, 5.2 +/- 1.0, and 4.0 +/
      0.9 at 1, 2, 3, and 4 weeks, and all they were smaller than those in the
      control, respectively (p < 0.05). It reached 137.4% of the density of
      hemidesmosomes in human cornea at 3 weeks. The average depths of anchoring fibril
      were 0.10 +/- 0.03, 0.27 +/- 0.06, 0.45 +/- 0.06, and 0.46 +/- 0.12 microm at 1,
      2, 3, and 4 weeks, reaching 75.0% of that in the human cornea after 3 weeks,
      although they were shallower than that of the control, respectively (p < 0.05).
      CONCLUSIONS: Assembly of adhesion complex in cultivated epithelium transplanted
      in limbal deficient rabbit might recover to the level of that in the human after
      3 weeks, although it was delayed compared with that in normal wound healing of
      the rabbit.

PMID- 16109644
TI  - Glutathione and lipid peroxide changes in pseudoexfoliation syndrome.
AB  - PURPOSE: To investigate the oxidative status of the aqueous humor of patients
      with pseudoexfoliation (PEX) syndrome. METHODS: Aqueous humor samples obtained
      during cataract surgery of patients with PEX syndrome and normal age-matched
      control subjects were examined for changes in the levels of glutathione (GSH),
      glutathione disulfide (GSSG), and TBA reactive species (TBARS), products of lipid
      peroxidation. GSH, GSSG, and TBARS were determined by specific fluorescent
      assays. RESULTS: Compared to normal controls, PEX syndrome aqueous humor samples
      showed a decrease of up to 28% of GSH concentration, and GSSG was increased up to
      23%. The ratio of GSH/GSSG was 1.7-fold decreased in PEX syndrome samples. TBARS
      levels were increased by 100% in the PEX aqueous humor samples as compared to the
      controls. CONCLUSIONS: High levels of GSSG and TBARS indicate high oxidative
      stress, as well as the decrease in the ratio of GSH/GSSG. Our findings suggest a
      role for oxidation stress in the pathogenesis and the progression of PEX
      syndrome.

PMID- 16109645
TI  - In vitro sustained human transscleral drug delivery of fluorescein-labeled
      dexamethasone and methotrexate with fibrin sealant.
AB  - PURPOSE: To study the use of fibrin sealant as a drug delivery system for the
      sustained transscleral delivery of dexamethasone and methotrexate. METHODS:
      Scleral sections excised from moist-chamber-stored human globes were mounted in a
      perfusion chamber. Dexamethasone-fluorescein or methotrexate-fluorescein in
      either fibrin sealant or balanced salt solution (BSS) was applied to the
      episcleral surface. BSS was perfused to the choroidal side, fluorescence was
      measured in perfusate fractions, and an apparent scleral permeability P(A) was
      calculated for each solute-vehicle combination. RESULTS: P(A) for both compounds
      was significantly lower with fibrin sealant delivery compared to delivery in BSS
      (p < 0.001). However, the fibrin sealant vehicle provided a more sustained
      release of both drugs through 24 hr. CONCLUSIONS: Incorporating dexamethasone and
      methotrexate into a fibrin sealant provided a more gradual drug delivery and a
      more uniform delivery compared to dissolving these drugs in BSS. Fibrin sealant
      could be useful for transscleral delivery for posterior segment disease.

PMID- 16109646
TI  - Prostaglandins E1 and E2, but not F2alpha or latanoprost, inhibit monkey ciliary
      muscle contraction.
AB  - PURPOSE: To investigate the effects of prostaglandin (PG) E1, E2, F2alpha, and
      latanoprost acid on the electrically evoked contractile response of isolated
      rhesus monkey ciliary muscle. METHODS: Longitudinal ciliary muscle preparations
      from rhesus monkeys were mounted in an organ bath, and tension changes were
      recorded by an isometric transducer. Electrical field stimulation (100 Hz, 0.3
      ms, 10 V) was applied through a pair of platinum plate electrodes. RESULTS: The
      ciliary muscle produced atropine-sensitive excitatory contraction in response to
      field stimulation. PGE1 and PGE2 (1 microM) attenuated the contraction to levels
      that were 68% and 65.1%, respectively, of the normal amplitude. However,
      PGF2alpha and latanoprost acid (1 microM) did not significantly change the
      response amplitude. CONCLUSIONS: Our results indicate that PGF2alpha and
      latanoprost acid do not interact with the prostanoid receptor involved at the pre
      and/or postsynaptic site. Therefore, it is unlikely that the hypotensive action
      by these agents is due to relaxation of the ciliary muscle.

PMID- 16109647
TI  - Choroidal ganglion cells in prenatal, young, and middle-aged human donor eyes.
AB  - PURPOSE: In the current study, the appearance and development of choroidal
      ganglion cells (CGCs) was investigated in eyes of 18 human donors between the
      13th week of gestation (wog) and 42 years of age. METHODS: The number and
      diameter of CGCs was evaluated in scleral and choroidal whole mounts stained for
      NADPH diaphorase. To demonstrate the synaptic input of the CGCs, sections were
      stained with antibodies against synaptophysin, vesicular acetylcholin
      transporter, tyrosin hydroxylase, and vesicular monoaminergic transporter 2.
      RESULTS: Clusters of small CGCs were first seen in the 18th wog next to the nasal
      and temporal long ciliary nerves. Immunohistochemistry in the 25th wog revealed
      3298 and 5429 nitric oxide synthase/NADPH diaphorase positive CGCs, surrounded by
      numerous cholinergic and aminergic boutons. The number of CGCs decreased to 1000
      2500 after birth. During postnatal development, the CGCs spread into small
      groups, distributed all over the choroid. The size of CGCs increased markedly up
      to adulthood. CONCLUSIONS: CGCs appear late during choroidal development, in
      parallel with the differentiation of the outer vascular layers. This coincidence
      might point to the primary role of the CGCs as specific vasoregulators in species
      with a well-developed fovea centralis.

PMID- 16109648
TI  - Experimental autoimmune uveitis induced by immunization with retinal pigment
      epithelium-specific 65-kDa protein peptides.
AB  - PURPOSE: To investigate the pathogenic potential and sites of retinal pigment
      epithelium-specific 65-kDa protein (RPE65) for inducing experimental autoimmune
      uveitis (EAU) in Lewis rats. METHODS: Twenty-six peptides were chemically
      synthesized based on the amino acid sequences of human RPE65. These peptides
      spanned the entire RPE65 sequence. Each peptide was injected into a footpad and
      the peritoneum of Lewis rats. The eyes were examined by slit-lamp biomicroscopy,
      and the findings were correlated with the histological findings. The serum
      antibody titer and lymphocyte reactivity against each peptide was also determined
      by enzyme-liked immunosorbent assay (ELISA) and lymphocyte proliferation assay,
      respectively. RESULTS: Active immunization of rats resulted in the induction of
      EAU with 14 (3 severe and 11 mild) of the 26 peptides. The clinical course of the
      EAU was similar to that induced by the injection of retinal antigens such as S
      antigen or inter-photoreceptor retinoid binding protein (IRBP). However, the
      histopathologic changes differed from the EAU induced by these retinal antigens.
      The inflammation was induced mainly from the retinal pigment epithelium (RPE) and
      the choroid, while the retina was relatively well-preserved except for some
      granulomatous changes adjacent to the RPE. CONCLUSIONS: Active immunization with
      peptides making up RPE65 will induce EAU. RPE65 has multiple EAU-inducing sites
      for Lewis rats.

PMID- 16109649
TI  - Systemic and periocular deliveries of plasminogen kringle 5 reduce vascular
      leakage in rat models of oxygen-induced retinopathy and diabetes.
AB  - PURPOSE: Increased retinal vascular permeability is a common complication of
      diabetes and a major cause of vision loss in diabetic patients. The current study
      is to determine the effect of plasminogen kringle 5 (K5) on vascular leakage via
      systemic and periocular deliveries. METHODS: Oxygen-induced retinopathy (OIR) was
      generated by exposing newborn rats to 75% oxygen. Diabetes was induced in adult
      rats by injection of streptozotocin (STZ). Retinal vascular permeability was
      measured by the Evans blue-albumin leakage method. RESULTS: Subcutaneous,
      intraperitoneal, subconjunctival, and retrobulbar injections and topical eyedrop
      application of K5 significantly reduced retinal vascular permeability in both the
      OIR and STZ-diabetic rat models. Compared with the periocular deliveries,
      systemic administration requires higher doses of K5. K5 deliveries downregulated
      VEGF expression in the retina. CONCLUSIONS: K5 can reduce retinal vascular
      permeability through systemic and periocular deliveries. These delivery routes of
      K5 have therapeutic potential in the treatment of vascular leakage.

PMID- 16109651
TI  - Functional changes in rod and cone pathways after photoreceptor loss in light
      damaged rats.
AB  - PURPOSE: To determine the functional changes in the rod and cone pathways after
      photoreceptor loss by continuous light exposure. METHODS: Fifty-four male Sprague
      Dawley rats were exposed to diffuse fluorescent light of 2000 lux for 24 or 48
      hr. Two weeks after the light exposure, full-field scotopic and photopic
      electroretinograms (ERGs) were elicited by different stimulus intensities with a
      maximum luminance of 0.84 log cd-s/m2. The amplitudes of the a- and b-waves of
      the scotopic ERGs and the b-wave of the photopic ERGs were measured. The animals
      were sacrificed after the ERG recordings, and the number of surviving rod and
      cone nuclei in the outer nuclear layer was counted. RESULTS: The logarithm (log)
      of the amplitudes of the maximum rod a-wave (rod Va(max)) and b-wave (rod
      Vb(max)) was reduced monotonically with a decrease in the rod nucleus counts (p <
      0.0001). The regression line for the rod Va(max) decrease was significantly
      steeper than that for the rod Vb(max) (p < 0.005). The maximum b-wave amplitudes
      of the photopic ERGs (cone Vb(max)) were significantly correlated with the number
      of cone nuclei in a log-linear fashion. The slopes of the regression lines for
      the rod Vb(max) and cone Vb(max) were 0.0067 and 0.0140, respectively, which
      indicates that the amplitude of the cone b-wave was more severely affected than
      that of the rod b-waves by light-induced photoreceptor degeneration (p < 0.005).
      CONCLUSIONS: The amplitudes of the rod and cone ERGs were correlated with rod and
      cone nuclei counts in a log-linear fashion in light-damaged rats. The functional
      loss from the photoreceptor death had a greater effect on the cone pathway than
      on the rod pathway when the retinal function was assessed by the b-wave.

PMID- 16109650
TI  - Nitrite-modified extracellular matrix proteins deleteriously affect retinal
      pigment epithelial cell function and viability: a comparison study with
      nonenzymatic glycation mechanisms.
AB  - PURPOSE: Extracellular matrix (ECM) plays an important role in the regulation of
      cell function. The aging process may involve chemical modifications to ECM
      proteins, which may contribute to the aging of the Bruch membrane and
      pathogenesis of age-related macular degeneration (AMD). The purpose of this study
      is to investigate nitrite modification of basement membrane-like proteins on RPE
      cell behavior as a model for the aging of the Bruch membrane in age-related eye
      diseases. As a comparison, retinal pigment epithelium (RPE) cell behavior on
      glycolaldehyde-modified matrices (GMM) was also studied. METHODS: Growth factor
      reduced Matrigel was reacted with nitrite or glycolaldehyde for 1 week or 12 hr,
      respectively. Calf RPE cells were plated on the modified matrices and examined in
      several ways. Attachment rates, proliferation rates, apoptosis, and necrosis were
      determined. Cell morphology and cell susceptibility to A2E-mediated damage was
      also monitored. RESULTS: Nitrite-modified matrices (NMMs) inhibited cell
      attachment by 65% and proliferation by 33.7% compared to 69.6% and 21.7%,
      respectively, by GMM. Proliferation inhibition was not significant when cells
      were plated at high density on GMM (3.47%) but significant on NMM (20.9%). NMM
      induced cell apoptosis and necrosis, but GMM induced cell apoptosis only. Both
      modifications inhibited RPE differentiation. RPE cells on both matrices were more
      susceptible to blue light mediated damage by A2E, but damage was greater on NMM.
      CONCLUSIONS: NMM has significant damaging effects on RPE cell function and
      viability that is similar to the damaging effects of GMM. These studies may have
      relevance to the RPE dysfunction observed during the progression of AMD.

PMID- 16109652
TI  - Long-term safety of GDNF gene delivery in the retina.
AB  - PURPOSE: To examine retinal function after the long-term, gene therapy-delivered
      expression of exogenous glial cell line-derived neurotrophic factor (GDNF).
      METHODS: Forty Sprague-Dawley rats each received an intravitreal injection of
      recombinant adeno-associated virus expressing GDNF (rAAV-GDNF) in their right
      eye. The left eye was untreated. One year after viral transduction in ocular
      tissues, retinal morphology and function were compared between rAAV-GDNF-injected
      and normal naive eyes. Synthesis and accumulation of GDNF within the retina were
      immunohistologically confirmed using enzyme-linked immunosorbent assay.
      Morphological analyses included light microscope examination of retinal sections
      and the counting of retinal ganglion cells. Inflammation by infiltration of
      leukocytes in retina was assessed immunohistochemically. Retinal function was
      assessed using electroretinography. RESULTS: GDNF expression was confirmed. There
      was no obvious abnormality in retinal section or increased infiltration by
      leukocytes after retinal transduction of rAAV-GDNF for 1 year. Counts of retinal
      ganglion cells were not decreased in rAAV-GDNF-injected eyes. There were no
      statistical differences in amplitude as well as latency of the electroretinogram
      determined a- and b-waves between transduced and untreated eyes. CONCLUSIONS:
      Long-term expression of GDNF within the eyes can be achieved by intravitreal
      injection of rAAV vectors in the absence of morphological or functional deficits
      in the retina.

PMID- 16109653
TI  - Expressions of urokinase-type plasminogen activator, its receptor and plasminogen
      activator inhibitor-1 in gastric cancer cells and effects of Helicobacter pylori.
AB  - OBJECTIVE: Destruction of the extracellular matrix is essential for tumor
      invasion and metastasis. The relationship between Helicobacter pylori (H. pylori)
      infection and destruction of the extracellular matrix is not yet clear. Urokinase
      type plasminogen activator (uPA) plays an important role in the destruction of
      the extracellular matrix and basement membrane. Urokinase-type plasminogen
      activator receptor (uPAR) and plasminogen activator inhibitor-1(PAI-1) appear to
      be associated with these processes. To clarify the role of H. pylori infection in
      the processes of destruction of the extracellular matrix and basement membrane in
      cancerous tissue, the effect of H. pylori on the expressions of uPA, uPAR and PAI
      1 in cancer cells was investigated. MATERIALS AND METHODS: Gastric cancer cell
      lines (MKN45, KATO-III) were co-cultured with H. pylori standard strain
      (NCTC11637), cagA-negative strain and clinical isolated strain. The specific
      inductions of uPA, uPAR and PAI-1 mRNA were examined by reverse transcription
      polymerase chain reaction (RT-PCR) amplification. The secreted uPA antigen was
      measured by enzyme-linked immunosorbent assay (ELISA). To evaluate the role of
      transcription factor NF-kappaB in uPA and uPAR gene transcription with H. pylori
      stimulation, the effect of NF-kappaB inhibitor MG132 on H. pylori-induced uPA and
      uPAR mRNA expression was examined. RESULTS: The expressions of both uPA and uPAR
      mRNAs in the gastric cancer cell lines (MKN45 and KATO- III) were increased
      markedly (uPA mRNA; MKN45: 12-fold, KATO-III: 5-fold) (uPAR mRNA; MKN45: 3-fold,
      KATO-III: 3-fold) with H. pylori NCTC11637 strain stimulation, whereas the
      expression levels of uPA and uPAR mRNA did not increase with cagA-negative strain
      stimulation. These cancer cell lines slightly secreted uPA antigen into the
      culture medium, and the amount of uPA antigen increased dramatically by
      stimulation with H. pylori NCTC11637 and cagA-positive clinical isolated strains.
      These gastric cancer cell lines also slightly secreted PAI-1 antigen into the
      culture medium, and the amount of PAI-1 antigen was not affected by H. pylori
      NCTC11637 stimulation. H. pylori-induced uPA and uPAR mRNA expressions were
      strongly down-regulated by pretreatment with MG132 in both cell lines.
      CONCLUSIONS: The results of this study indicated the possibility that cagA
      positive H. pylori may play an important role not only in tissue remodeling,
      angiogenesis and wound healing but also in the process of degradation of the
      extracellular matrix breakdown, tumor invasion and metastasis by inducing uPA and
      uPAR complex in the gastric cancer cells.

PMID- 16109654
TI  - Evaluation of Helicobacter pylori with a stool antigen assay in frail, elderly
      patients.
AB  - OBJECTIVE: Helicobacter pylori infection has not been studied thoroughly in
      elderly patients. The aim of this study was to evaluate the reliability of stool
      antigen assay (HpSA) in the assessment of H. pylori infection in hospitalized,
      frail, elderly patients. MATERIALS AND METHODS: The study population consisted of
      85 consecutively recruited elderly patients (> or =65 years old) hospitalized
      between May 1999 and December 2001 with diagnostic indications for upper
      gastrointestinal endoscopy. Twenty-nine subjects had been receiving treatment
      with proton-pump inhibitors (PPIs), such as omeprazole (10-20 mg/day) for 2-15
      days, and 56 were not receiving treatment. HpSA was evaluated versus UBT (urea
      breath test), serology and histology: patients with at least two positive results
      out of the latter three tests were considered positive for H. pylori infection,
      while patients with at least two negative tests out of three were considered
      negative. RESULTS: The sensitivity and specificity of HpSA in the 56 untreated
      patients were, respectively, 76% (true positives TP = 22; false negatives FN = 7)
      and 93% (true negatives TN = 25; false positives FP = 2). The sensitivity and
      specificity of HpSA in the 29 patients on PPI treatment were, respectively, 82%
      (TP = 9; FN = 2) and 83% (TN = 15; FP = 3). CONCLUSIONS: HpSA is an accurate, non
      invasive and easy method for diagnosing H. pylori infection in elderly patients.

PMID- 16109655
TI  - Food-specific IgG4 antibody-guided exclusion diet improves symptoms and rectal
      compliance in irritable bowel syndrome.
AB  - OBJECTIVE: Dietary modification improves symptoms in irritable bowel syndrome
      (IBS). Identification of offending foods by dietary elimination/re-challenge is
      cumbersome. IgG4 antibodies to common food antigens are elevated in IBS. The aim
      of this article was to evaluate the effect of exclusion diet based on IgG4 titres
      on IBS symptoms and rectal sensitivity and compliance. MATERIALS AND METHODS: The
      study comprised 25 patients with IBS (3 M, 22 F, mean age 43 years, Rome II
      criteria). IgG4 titres to 16 foods (milk, eggs, cheese, wheat, rice, potatoes,
      chicken, beef, pork, lamb, soya bean, fish, shrimps, yeast, tomatoes and peanuts)
      were measured. Foods with titres >250 microg/l were excluded for 6 months.
      Symptom severity was assessed with a previously validated questionnaire at
      baseline, at 3 months and at 6 months. Rectal compliance and sensitivity were
      measured in 12 patients at baseline and at 6 months. RESULTS: IgG4 antibodies to
      milk, eggs, wheat, beef, pork and lamb were commonly elevated. Significant
      improvement was reported in pain severity (p < 0.001), pain frequency (p =
      0.034), bloating severity (p = 0.001), satisfaction with bowel habits (p = 0.004)
      and effect of IBS on life in general (p = 0.008) at 3 months. Symptom improvement
      was maintained at 6 months. Rectal compliance was significantly increased (p =
      0.011) at 6 months but the thresholds for urge to defecate/discomfort were
      unchanged. CONCLUSIONS: Food-specific IgG4 antibody-guided exclusion diet
      improves symptoms in IBS and is associated with an improvement in rectal
      compliance.

PMID- 16109656
TI  - Stimulation of defecation: effects of coffee use and nicotine on rectal tone and
      visceral sensitivity.
AB  - OBJECTIVE: Coffee and cigarette use is believed to induce bowel movements,
      although the literature is controversial and precise measurements of rectal tone
      and sensitivity with a barostat have never been performed. The aim of this study
      was to assess the effects of coffee and nicotine on rectal tone, compliance and
      sensitivity. MATERIALS AND METHODS: Sixteen healthy volunteers were recruited for
      the coffee (n = 8) and nicotine (n = 8) experiments. The experiments were
      randomly performed in a placebo-controlled crossover design on separate days. In
      the coffee experiment, 280 ml strong coffee or warm water was drunk and in the
      nicotine experiment, nicotine (2 mg) or placebo was given sublingually. A rectal
      barostat procedure was carried out. A flaccid bag, mounted on a catheter, was
      inserted in the rectum. Continuous pressure distension was exerted to register
      basal visceral sensitivity and compliance. After rectal adaptation, the stimulus
      was given. Rectal tone was measured for 1 h, after which continuous pressure
      distension was repeated. RESULTS: Rectal tone increased by 45% 30 min after
      coffee intake (p = 0.031) and by 30% after water intake (p = 0.032), but the
      effects of coffee and water were not significantly different. Rectal tone did not
      change significantly after administration of nicotine (7%) or placebo (10%).
      There was no difference in compliance and visceral sensitivity between coffee and
      water or nicotine and placebo. CONCLUSIONS: Both coffee and warm water have an
      effect on defecation by increasing rectal tone, but nicotine (2 mg) did not
      affect rectal tone. Coffee and nicotine did not influence sensitivity or
      compliance.

PMID- 16109657
TI  - Alteration of gastric myoelectrical and autonomic activities with audio
      stimulation in healthy humans.
AB  - OBJECTIVE: Cold or emotional stress was reported to affect gastric myoelectrical
      activity. The aim of this study was to investigate the effects of music or noise
      on gastric myoelectrical activity and autonomic function in healthy volunteers.
      MATERIALS AND METHODS: The study was performed in 10 fasted healthy volunteers
      and included 30 min at baseline, 30 min of classical music via headphones and 30
      min of loud household noises via headphones. The electrogastrogram (EGG) readings
      were recorded simultaneously with the electrocardiogram (ECG) recording. RESULTS:
      Both classical music and noise altered the regularity of gastric slow waves. The
      percentage of normal 2-4 cycles/min (cpm) waves was reduced from 77.9 +/- 4.7% at
      baseline to 66.9 +/- 5.4% during music (p < 0.006) and 67.7 +/-5.4% during noise
      (p < 0.05). The reduction was attributed to a significant increase in
      bradygastria (15.8 +/- 3.9% versus 9.8 +/- 2.6%, p < 0.04) with the music and a
      significant increase in arrhythmia (7.4 +/- 1.6% versus 2.0 +/- 1.1%, p < 0.02)
      with the noise. The dominant frequency and power of the EGG were, however, not
      altered with either music or noise. Neither music nor noise had any effect on the
      autonomic function assessed by the heart rate variability. CONCLUSIONS: Audio
      stimulation, with both music and noise, alters the rhythmicity of gastric slow
      waves. Classical music seems to increase bradygastria, whereas, household noise
      may increase arrhythmia. The effect of audio stimulation on the gastric slow wave
      does not seem to involve sympathetic or vagal efferent pathways assessed by the
      spectral analysis of heart rate variability.

PMID- 16109658
TI  - Lactose intolerance: lactose tolerance test versus genotyping.
AB  - OBJECTIVE: Adult lactose intolerance, which affects the majority of the
      population in the world, has been associated with a single nucleotide
      polymorphism, C-13910T, located upstream of the lactase gene. MATERIAL AND
      METHODS: Adult patients undergoing lactose tolerance tests with lactose challenge
      and plasma glucose measurements were included in the study comprising 44 Swedes
      and 7 non-Swedish individuals. A real-time PCR method was established for the
      genotyping. RESULTS: Out of 51 patients 48 had concordant results on genotyping
      and lactose tolerance tests, e.g. -13910T/T and -13910C/T genotypes had high
      glucose elevations. All patients with the heterozygous genotype, -13910C/T, had
      high glucose elevations, and no gene-dose relationship was observed when
      comparing maximal glucose increases for cases with -13910C/T and -13910T/T
      genotypes. CONCLUSIONS: Genotyping could replace lactose challenge as a first
      stage screening test in adults of European descent, but should be used together
      with tolerance tests in children and patients where secondary lactose intolerance
      is suspected.

PMID- 16109659
TI  - IL-1 receptor antagonist (IL-1Ra) gene polymorphism in patients with inflammatory
      bowel disease in India.
AB  - OBJECTIVE: An association between polymorphism in the gene coding for the anti
      inflammatory cytokine interleukin-1-receptor antagonist (IL-1Ra) and ulcerative
      colitis (UC) has been reported. To date, there is no report from India confirming
      this association. In the present study the aim was to assess the allele
      frequencies and carriage rates of different alleles of 86 bp (base pair) variable
      number tandem repeat (VNTR) in intron 2 of the IL-1Ra gene in patients with
      inflammatory bowel disease (IBD) and healthy controls from northern India.
      MATERIAL AND METHODS: Eighty-two patients with UC, 21 with Crohn's disease (CD)
      and 141 ethnically matched controls were enrolled in this study. Genotyping was
      done using a polymerase chain reaction (PCR) amplification of the intron-2
      fragment harboring a VNTR nucleotide sequence. The PCR products were separated on
      2% agarose gel. Statistical analysis was performed using the chi-squared (chi(2))
      test. RESULTS: The frequencies of allele 2 in UC, CD and healthy controls were
      26%, 50% and 24%, respectively. The frequency of allele 2 in CD was higher than
      that in UC (p = 0.002; OR = 2.9) and healthy controls (p = 0.001; OR = 3.1; 95%
      CI = 1.5-6.3). Alleles 3 and 4 were absent in patients with CD, while allele 5
      was absent in all three groups. CONCLUSIONS: The present study demonstrated an
      association between allele 2 and patients with CD but not with UC. Interestingly,
      the allele frequency and carriage rates of allele 2 were significantly higher in
      patients with CD than in patients with UC and in healthy subjects. Ethnic
      differences, genetic heterogeneity and sample size could be the reasons for such
      differences in comparison with studies from the West.

PMID- 16109660
TI  - Magnetic resonance imaging of the small bowel in Crohn's disease.
AB  - OBJECTIVE: There may be advantages in using magnetic resonance imaging (MRI) in
      small-bowel disease. The aims of this study were to optimize the MRI examination
      technique and to evaluate the capabilities of MRI compared with those of
      conventional enteroclysis (CE). MATERIALS AND METHODS: MRI and CE were performed
      in 36 patients suspected of Crohn's disease. Based on 26 pilot studies optimal
      oral administration of plum juice and bulk fibre laxative was found. T2-weighted
      and gadolinium enhanced T1-weighted images were obtained using a breath-holding
      technique and butylscopolamine. Virtual endoscopy was performed. Conventional
      enteroclysis entailed duodenal intubation and administration of barium and air.
      Two radiologists evaluated the examinations independently. Finally, each patient
      scored the degree of discomfort, and preference for either MRI or CE was found.
      RESULTS: The MRI technique ensured sufficient distension of the small bowel and
      small-bowel changes were found in 12 patients. In 3 patients this was not seen on
      conventional enteroclysis, which did not reveal any pathology that was not
      already seen on MRI. Pathological abdominal changes were found in 70% more
      patients during MRI than during conventional enteroclysis (p < 0.001). Endoscopic
      examination corresponded with the MRI findings. The examination quality decreased
      with increasing age (p = 0.002) and the interobserver agreement of the
      pathological changes was high (p < 0.001). Virtual endoscopy resulted in
      excellent demonstration of the mucosal surface. The examination discomfort scores
      obtained during the MRI were lower than those during conventional enteroclysis (p
      < 0.001). CONCLUSIONS: MRI using the current technique is preferable to
      conventional enteroclysis because of superior demonstration of the entire small
      bowel pathology, low level of patient discomfort and absence of radiation
      exposure.

PMID- 16109661
TI  - Disseminated tumor cells in the blood of patients with gastric cancer are an
      independent predictive marker of poor prognosis.
AB  - OBJECTIVE: Gastric cancer carries a poor prognosis even after curative resection
      (R0). Tumor progression in gastric cancer patients has been attributed to the
      persistence of disseminated tumor cells (DTC) in various body compartments as a
      sign of minimal residual disease, although the prognostic relevance of DTC is
      still unclear. In this study the prognostic relevance of DTC in the blood of
      gastric cancer patients was investigated. MATERIALS AND METHODS: Venous blood
      samples of 70 cancer patients were taken intraoperatively before surgical
      manipulation and examined by reverse transcription-polymerase chain reaction (RT
      PCR) for expression of cytokeratin 20 (CK20) as a marker for DTC. Tumor-related
      survival was analyzed using univariate and multivariate models assessing
      occurrence of DTC, residual tumor classification, and tumor stage. Median follow
      up was 20 months (range 1-57 months). RESULTS: Twenty-eight of the 70 patients
      (40%) were CK20 positive. The prevalence of DTC in patients following R0
      resection (15/41, 37%) was similar to that in patients with residual tumor
      (13/29, 45%, NS). Furthermore, expression of CK20 was independent of TNM stage.
      Univariate analysis of R0-resected patients revealed CK20 to be a marker for
      significantly shorter tumor-related survival (p = 0.0363). In a multivariate
      analysis, CK20 was an independent prognostic marker. Detection of CK20 had
      greatest impact for early tumor stages (T1 and T2, N0; p < 0.0032). CONCLUSIONS:
      Detection of DTC in venous blood of gastric cancer patients is an independent
      predictive marker of poor prognosis and thus could help to define patients for
      adjuvant therapy with this tumor entity.

PMID- 16109662
TI  - Aldosterone enhances 11beta-hydroxysteroid dehydrogenase type 2 expression in
      colonic epithelial cells in vivo.
AB  - OBJECTIVE: [corrected] 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2)
      metabolizes glucocorticoids, thus enabling aldosterone to bind to the
      mineralocorticoid receptor. However, little is known about the regulatory
      mechanism of epithelial 11beta-HSD2 expression in the gut. MATERIALS AND METHODS:
      Sprague-Dawley rats were maintained on a sodium-depleted diet or subjected to
      continuous aldosterone infusion for 4 weeks. Plasma aldosterone and arginine
      vasopressin (AVP) levels were measured by radioimmunoassay. Expression of 11beta
      HSD2 in colonic epithelia was evaluated by Northern blotting and
      immunohistochemistry. T84 and Caco2 cells were stimulated with aldosterone,
      dexamethasone and AVP alone or in combination, and 11beta-HSD2 mRNA was measured
      by quantitative reverse transcription polymerase chain reaction (RT-PCR).
      RESULTS: Sodium-depleted and aldosterone-infused rats showed an increase of
      plasma aldosterone and AVP. Both treatments resulted in induction of 11beta-HSD2
      in the colonic epithelia at mRNA and protein levels. Positive immunoreactivity
      was detected in the cytoplasm of the surface epithelia in control rats. In
      contrast, epithelial cells in the crypt also showed immunoreactivity for 11beta
      HSD2 in the proximal colon of dietary sodium-depleted and aldosterone-infused
      rats. Induction of 11beta-HSD2 mRNA was observed when T84 cells were stimulated
      with corticosteroids plus AVP. CONCLUSIONS: Aldosterone has a pivotal role by
      increasing expression of 11beta-HSD2 in epithelial cells of the colon. AVP may
      act as a synergistic hormone in aldosterone-mediated 11beta-HSD2 induction.

PMID- 16109663
TI  - Distribution of lymph node metastasis in T1 sigmoid colon carcinoma: should we
      ligate the inferior mesenteric artery?
AB  - OBJECTIVE: In standard oncological sigmoid colectomy, the inferior mesenteric
      artery is ligated either at its origin or at the level of the left colic artery.
      However, in patients with early-stage carcinoma, the distribution of metastatic
      nodes may be limited. The aim of this study was to clarify the prevalence and
      distribution of lymph node metastasis in T1 sigmoid colon carcinoma and to
      determine the adequate range of lymph node dissection. MATERIALS AND METHODS: The
      study included 121 consecutive patients treated for T1 sigmoid colon carcinoma.
      Clinicopathologic factors associated with nodal metastasis and the distribution
      of metastatic nodes were analyzed. RESULTS: Of 121 patients, 12 (10%) had nodal
      involvement. The depth of invasion and the presence of lymphatic and vascular
      invasion were significantly associated with nodal metastasis. Of these 12
      patients, 11 (92%) had lymph node metastasis confined to pericolic nodes. Nodes
      along the sigmoidal artery were involved in one patient. There was no involved
      node along the superior rectal artery or at the root of the inferior mesenteric
      artery. CONCLUSIONS: Lymph node dissection for T1 sigmoid colon carcinoma should
      be limited to the root of the sigmoidal artery, and the inferior mesenteric
      artery should be preserved.

PMID- 16109664
TI  - Cholestasis in acute stroke: an investigation on its prevalence and etiology.
AB  - OBJECTIVE: Liver cholestatic enzymes and/or bilirubin occasionally occur in acute
      stroke and are usually, but not always, ascribed to comorbid conditions. We
      investigated the frequency and possible etiology of this phenomenon. MATERIAL AND
      METHODS: Prospective evaluation of post-admission biochemical cholestasis of all
      patients hospitalized with acute stroke was conducted during a 21-month period.
      RESULTS: Of 169 consecutive patients, 18 (10.7%) developed cholestasis. In 7 of
      the patients (4.1%; 4 M, 3 F, median age 70 years, range 57-82 years) no apparent
      cause of cholestasis could be found, and they were further evaluated (Group A).
      These patients were compared with 21 randomly selected stroke patients without
      cholestasis, matched for age and gender, and who acted as controls (Group B).
      Group A patients were in a deeper coma than the controls (Glasgow Coma Scale 3.4
      +/- 0.8 versus 1.9 +/- 0.7, p < 0.001), associated with severe autonomic and
      hypothalamic involvement, while no such manifestations were present in Group B (p
      < 0.001). Cholestasis started on the 3rd-6th day and lasted up to the 11th-25th
      day, with maximum median levels of gamma-GT and serum alkaline phosphatase (SAP)
      of up to 4.38 (range 2.33-8.25) and 1.49 (range 0.63-2.56) times the upper limit
      of normal, respectively. Serum alanine aminotransferase (ALAT), total and direct
      bilirubin increased in Group A but not in Group B. The common bile duct was
      significantly wider in Group A than in Group B (7.7 +/- 0.5 versus 4.7 +/- 0.6
      mm, p < 0.001) and within Group A during and after cholestasis (7.7 +/- 0.5
      versus 4.7 +/- 0.5 mm, p < 0.001). CONCLUSIONS: Transient cholestasis may occur
      in 4.1% of patients following acute stroke. Cholestasis is associated with deeper
      coma, autonomic and hypothalamic involvement and common bile duct dilatation
      without obstruction, possibly related to inordinate hypertonia of the sphincter
      of Oddi.

PMID- 16109665
TI  - Cirrhosis in hepatitis C virus-infected patients can be excluded using an index
      of standard biochemical serum markers.
AB  - OBJECTIVE: Assessment of liver histology is pivotal in prognostication and
      decision-making regarding therapeutic intervention in patients with chronic
      hepatitis C virus (HCV). Being an invasive procedure, the liver biopsy is
      associated with complications, and a non-invasive alternative would be
      preferable. MATERIAL AND METHODS: Sera samples from 179 patients with chronic HCV
      infection collected at the time of liver biopsy were analyzed using routinely
      available biochemical markers of liver disease, and liver histology was evaluated
      using the Ishak protocol. The relationship between the serum biochemical markers
      and cirrhosis (Ishak stage > or = 5) as well as bridging fibrosis (Ishak stage >
      or = 3) was examined. RESULTS: A strong association was found in the multivariate
      logistic regression analysis between fibrosis stage and aspartate
      aminotransferase (AST), platelet count and prothrombin-INR (international
      normalized ratio). An index (the Goteborg University Cirrhosis Index (GUCI)) was
      calculated using these variables: normalized ASTxprothrombin-INRx100/platelet
      count (x 10(9)/l). Using a cut-off value of 1.0, the sensitivity was 80% and the
      specificity 78% for diagnosis of cirrhosis, and the negative predictive values
      (NPV) and positive predictive values (PPV) were 97% and 31%, respectively. The
      GUCI score proved slightly superior for sensitivity, specificity, NPV, PPV, and
      the area under the receiver operating characteristic (ROC) curve for prediction
      of cirrhosis and bridging fibrosis compared with the AST to platelet ratio index
      (APRI), which has been reported as a predictor of significant fibrosis and
      cirrhosis. CONCLUSION: An index using routinely available biochemical markers can
      with a high degree of accuracy discriminate patients with from those without
      hepatitis C-related cirrhosis.

PMID- 16109666
TI  - Effects of alendronate on bone mass in patients with primary biliary cirrhosis
      and osteoporosis: preliminary results after one year.

PMID- 16109668
TI  - Ischaemic colitis mimicking inflammatory bowel disease in a young adult receiving
      oral anticoagulation.
AB  - Ischaemic colitis (IC) is the most frequent form of gastrointestinal ischaemia.
      Discrepancy between non-specific symptoms and objective findings is a hallmark of
      IC. Thus delay of diagnosis is common due to its often subtle and unpredictable
      presentation. In particular, the clinical symptoms and signs of IC can overlap
      with those of inflammatory bowel disease. We present a case of a young man with
      known factor-V-Leiden mutation in whom IC developed during effective therapy with
      oral anticoagulants, presenting with symptoms and endoscopic findings suggestive
      of inflammatory bowel disease.

PMID- 16109667
TI  - Inflammatory pseudotumor of the liver revealing gynecological Corynebacterium
      infection.
AB  - Inflammatory pseudotumor (IPL) of the liver is a rare benign clinicopathologic
      entity, which has been associated with infectious conditions, including
      alimentary, digestive tract and mouth infections. We report a new case, where a
      patient developed hepatic IPL that revealed endometritis related to
      Corynebacterium infection; the patient had a favorable outcome of hepatic IPL
      after appropriate antibiotic therapy initiation. Our findings therefore confirm
      that antibiotic therapy may be effective in patients with hepatic IPL associated
      with underlying infections, avoiding unnecessary surgery. Our data also indicate
      that when hepatic IPL is observed, a complete clinical evaluation, including
      gynecological evaluation, should be systematically performed.

PMID- 16109669
TI  - International consensus on meningitis and cochlear implants.

PMID- 16109670
TI  - International consensus on bilateral cochlear implants and bimodal stimulation.

PMID- 16109671
TI  - International consensus on middle ear implants.

PMID- 16109672
TI  - Cochlear temperature correlates with both temporalis muscle and rectal
      temperatures. Application for testing the otoprotective effect of hypothermia.
AB  - CONCLUSIONS: During systemic hypothermia, the internal temperature of the rat
      cochlea correlates best with the temporalis muscle and rectal temperatures. These
      positive correlations will be used in future studies to assess the efficacy of
      mild and moderate hypothermia to protect hearing against the progressive loss
      caused by electrode insertion in a clinically relevant model of cochlear
      implantation trauma. OBJECTIVE: To monitor the internal temperature of the
      cochlea during induced systemic hypothermia using a reference tissue instead of
      an internal cochlear temperature probe. MATERIAL AND METHODS: The temperatures of
      the cochlea, brain, temporalis muscle and rectum were determined during periods
      of normothermia (37 degrees C), mild (33 degrees C) and moderate (30 degrees C)
      hypothermia and slow rewarming in anesthetized adult Fisher rats. These values
      were compared using statistical analysis to establish the best correlations
      between the temperature of the cochlea and the temperature at the three other
      temperature measurement sites. RESULTS: The strongest correlations with the
      internal temperature of the cochlea during the induction of mild-to-moderate
      hypothermia were obtained for the temperatures of the ipsilateral temporalis
      muscle and rectum.

PMID- 16109673
TI  - Long-term follow-up after acute unilateral vestibular loss and comparison between
      subjects with and without remaining symptoms.
AB  - CONCLUSIONS: About half of the subjects in this study reported remaining symptoms
      3-6 years after acute unilateral vestibular loss. Differences could be seen
      between subjects with and without remaining symptoms regarding health-related
      quality of life, anxiety and depression. OBJECTIVE: To evaluate the presence of
      self-rated remaining symptoms 3-6 years after acute unilateral vestibular loss,
      and to compare subjects with and without such symptoms. MATERIAL AND METHODS:
      Firstly, 51 subjects answered a questionnaire which included the EuroQol EQ-5D,
      the Hospital Anxiety and Depression Scale, the University of California Los
      Angeles Dizziness Questionnaire, visual analogue scales and the Dizziness
      Handicap Inventory. Secondly, nine subjects with and nine without remaining
      symptoms participated in an extended testing procedure, including
      electronystagmography (ENG), determination of vestibular-evoked myogenic
      potentials (VEMPs) and clinical balance tests. RESULTS: In the first part of the
      study, 27 subjects reported remaining symptoms, 3 reported 1 additional period of
      symptoms and 21 had not experienced any symptoms at all in the 3-6 years since
      acute unilateral vestibular loss. In the second part, the group with remaining
      symptoms rated a lower health-related quality of life and a higher level of
      anxiety and depression. There were no differences between the two groups in terms
      of ENG tests, VEMPs or clinical balance tests.

PMID- 16109675
TI  - Scanning electron microscopic study of the muscle fiber arrangement in the rat
      cricopharyngeal muscle.
AB  - CONCLUSIONS: Myomyous junctions comprise a complex muscle fiber network, which is
      thought to synchronize the activity of the cricopharyngeal (CP) muscle fibers.
      Myomyous and myotendinous junctions explain the heterogeneity in muscle fiber
      length which contributes to the efficient behavior of the muscle. This scanning
      electron microscopy (SEM) study demonstrated the complex muscle fiber arrangement
      of the CP muscle and improved on the previous description of its morphological
      specificity. OBJECTIVE: To examine the 3D ultrastructure of the inferior
      pharyngeal constrictor muscle fibers to obtain further knowledge of their
      morphological characteristics with regard to the specific functions of the muscle
      in deglutition. MATERIAL AND METHODS: Six adult rats were used. Their CP and
      thyropharyngeal (TP) muscles were obtained and processed using the HCl hydrolysis
      method to remove i.m. connective tissue. The fine muscle fiber structure was
      observed by means of SEM. RESULTS: Multifaceted muscle fiber interconnections
      (myomyous junctions) were identified in the CP muscle. The myomyous junctions
      were characterized by the tight connection of many finger-like processes at the
      ends of a lateral branch or bifurcating trunk of the muscle fibers. In addition,
      muscle fibers occasionally tapered and ended within the muscle belly, forming
      myotendinous junctions. The TP muscle lacked these structures.

PMID- 16109674
TI  - A CD14 gene polymorphism is associated with the IgE level for Dermatophagoides
      pteronyssinus.
AB  - CONCLUSION: CD14/-159 plays a role in sensitization to Dermatophagoides
      pteronyssinus in Japanese patients with allergic rhinitis. OBJECTIVE: An
      association between a polymorphism in the 5'-flanking region of the CD14 gene and
      atopic phenotypes has been identified in a pediatric American population and an
      adult Dutch population. The aim of this study was to determine whether the CD14/
      159 polymorphism is associated with specific IgE levels in allergic rhinitis
      patients in a Japanese population. MATERIAL AND METHODS: The CD14/-159 genotypes
      of 81 unrelated patients with allergic rhinitis and 78 healthy subjects were
      determined and compared. The total IgE level and the specific IgE levels for
      three aeroallergens were determined. The IgE levels for each genotype were
      compared. RESULTS: The frequencies of CD14/-159 genotypes did not differ between
      the two groups. Among the allergic rhinitis patients, TT homozygotes had
      significantly fewer positive CAP-radioallergosorbent tests (CAP-RASTs) than CC
      homozygotes and CT heterozygotes, suggesting that the C allele is dominant. TT
      homozygotes also had significantly lower CAP-RAST scores for Dermatophagoides
      pteronyssinus, but not for Cryptomeria japonica or Dactylis glomerata, than CC
      homozygotes and CT heterozygotes. There was no significant association between
      total serum IgE levels and CD14/-159 genotypes in the allergic rhinitis patients.

PMID- 16109676
TI  - First clinical experience with a new non-indwelling voice prosthesis (Provox NID)
      for voice rehabilitation after total laryngectomy.
AB  - CONCLUSION: The new Provox NID non-indwelling voice prosthesis investigated in
      this study provides a good option for laryngectomized patients using non
      indwelling voice prostheses and can potentially improve safety and increase
      patients' satisfaction with their voice and speech. OBJECTIVE: To investigate the
      feasibility of and patient satisfaction with the Provox NID non-indwelling voice
      prosthesis. MATERIAL AND METHODS: Pre- and post-study questionnaires were used to
      evaluate the patients' former voice prosthesis and the Provox NID voice
      prosthesis. In addition, measurements of pull-out force, maximum phonation time
      and loudness were made for both voice prostheses. In vitro measurements of
      airflow characteristics were also made. Following a 6-week trial, all patients
      provided feedback on the new voice prosthesis and the results were used to
      further improve the Provox NID. This final version of the new voice prosthesis
      was subsequently trialled and evaluated by 10 patients 6 months later. RESULTS:
      Overall results showed that patient satisfaction with the Provox NID non
      indwelling voice prosthesis was favourable. The pull-out force for the new
      prosthesis was significantly higher than that for the formerly used prosthesis
      and its aerodynamic characteristics were better.

PMID- 16109678
TI  - Values, policies, and the public trust.

PMID- 16109679
TI  - Oversimplifications I: physicians don't do public health.

PMID- 16109680
TI  - Examining the potential exploitation of UNOS policies.
AB  - The United Network for Organ Sharing (UNOS) waiting list was designed as a just
      and equitable system through which the limited number of organs is allocated to
      the millions of Americans in need of a transplant. People have trusted the system
      because of the belief that everyone on the list has an equal opportunity to
      receive an organ and also that allocation is blind to matters of financial
      standing, celebrity or political power. Recent events have revealed that certain
      practices and policies have the potential to be exploited. The policies addressed
      in this paper enable those on the list with the proper resources to gain an
      advantage over other less fortunate members, creating a system that benefits not
      the individual most in medical need, but the one with the best resources. These
      policies are not only unethical but threaten the balance and success of the
      entire UNOS system. This paper proposes one possible solution, which seeks to
      balance the concepts of justice and utility.

PMID- 16109681
TI  - Another kind of end-run: status upgrades.

PMID- 16109682
TI  - UNOS: the faithless trustee.

PMID- 16109683
TI  - Are organs personal property or a societal resource?

PMID- 16109684
TI  - Who is really hurt anyway? The problem of soliciting designated organ donations.

PMID- 16109685
TI  - Gay and lesbian exceptions to the heterosexual rule.

PMID- 16109686
TI  - Using personal narratives to encourage organ donation.

PMID- 16109687
TI  - Make it so!: advocating for UNOS policy change.

PMID- 16109688
TI  - LifeSharers: increasing organ supply through directed donation.

PMID- 16109689
TI  - Non-family directed donation: the perils of policy-making.

PMID- 16109690
TI  - Trust and transplants.

PMID- 16109691
TI  - Reflections on fairness in UNOS allocation policies.

PMID- 16109692
TI  - My organs, my choice.

PMID- 16109693
TI  - What's blood got to do with it? It's time to say goodbye to directed cadaveric
      donation.

PMID- 16109694
TI  - Funding agendas: has bioterror defense been over-prioritized?
AB  - Post-9/11, concern about bioterrorism has transformed public health from
      unappreciated to a central component of national security. Within the War on
      Terror, bioterrorism preparedness has taken a back seat only to direct military
      action in terms of funding. Domestically, homelessness, joblessness, crime,
      education, and race relations are just a few of a litany of pressing issues
      requiring government attention. Even within the biomedical sciences and
      healthcare, issues surrounding the fact that more than 40 million Americans lack
      health insurance, the rising cost of prescription medications, and the use of
      government funds for research using embryonic stem cells remain unresolved.
      Should we prioritize a hypothetical threat (bioterrorism), or existing conditions
      that have implications for identifiable individuals? Even more fundamentally,
      should we prioritize research aimed at defense from bioterrorism (or even
      terrorism in general) when there are so many pressing social problems that affect
      the U.S. population?

PMID- 16109695
TI  - Finding a space for the public's health in bioterrorism funding: a commentary.

PMID- 16109696
TI  - Bioterrorism defense education: prioritizing public health education.

PMID- 16109697
TI  - Democratic defense spending in an age of bioterrorism.

PMID- 16109698
TI  - Biodefense: spend, but spend wisely.

PMID- 16109699
TI  - On economic justifications of bioterrorism defense spending.

PMID- 16109700
TI  - The biases of bioterror funding.

PMID- 16109703
TI  - Fungal types and concentrations from settled dust in normal residences.
AB  - Analysis of settled dust collected from carpeting and furnishings is occasionally
      used by investigators to determine whether an environment contains unusual fungi.
      Little information is available concerning the types and concentrations of
      culturable fungi present on textile surfaces in normal residential settings not
      affected by unusual mold reservoirs, such as from fungal growth sites within the
      built environment. This study presents the results of the collection and analysis
      of surface dust from 26 residential environments that were prescreened by
      interview, physical inspection, and air sampling to limit the surface dust
      collection to structures in which there was no history of water intrusion,
      flooding, plumbing leaks, signs of mold growth, or evidence of unusual airborne
      fungal spore types or concentrations. In those structures found to have no
      history or indications of water events or unusual fungi, surface dust was
      vacuumed from prescribed horizontal areas on carpet and textile-covered
      furnishings. These samples were then subjected to fungal culture, from which
      viable colonies were enumerated and identified. Based on the study results, it
      does not appear reasonable that the frequently quoted total fungi concentration
      exceeding 10(5) CFU/g is definitive evidence that a residential surface is
      contaminated with unusual amounts of culturable fungi. Collocated samples
      collected from eight side-by-side carpets sections revealed poor reproducibility.
      While settled dust sampling may be appropriate for determining the fungal status
      of a localized area, or as a gross screening tool, using settled dust results
      alone to establish the presence of unusual fungal types or concentrations within
      a structure appears to be inappropriate, and using settled dust results with
      other investigative methods, such as visual observations and air sampling,
      requires cautious interpretation.

PMID- 16109704
TI  - The logical basis of phylogenetic taxonomy.
AB  - Phylogenetic taxonomy, like modern Linnean taxonomy, was modeled on a
      phylogenetic tree rather than a cladogram and, like its predecessor, perpetuates
      the use of morphology as a means of recognizing clades. Both practices have
      generated confusion in graphical representation, operational terminology, and
      definitional rationale in phylogenetic taxonomy, the history of which is traced.
      The following points are made: (1) cladograms, rather than trees or hybrid
      cladogram-trees, provide the framework for the simplest graphical depiction of
      phylogenetic definitions; (2) a complete notational scheme for phylogenetic
      definitions is presented that distinguishes symbolic notation from shorthand and
      longhand versions; (3) phylogenetic definitions are composed of three components
      (paradigm, specifier, qualifier) arranged in two fundamental patterns-node and
      stem; (4) apomorphies do not constitute a fundamental definitional pattern but
      rather serve to qualify a stem-based definition (as do time and geographic
      range); (5) formulation of phylogenetic definitions involves three heuristic
      criteria (stability, simplicity, prior use); (6) reasoned definitional revision
      is encouraged and better defined (textual substitution, first-and second-order
      revision); and (7) a database, TaxonSearch, allows rapid recall of taxonomic and
      definitional information.

PMID- 16109705
TI  - Untangling long branches: identifying conflicting phylogenetic signals using
      spectral analysis, neighbor-net, and consensus networks.
AB  - Long-branch attraction is a well-known source of systematic error that can
      mislead phylogenetic methods; it is frequently invoked post hoc, upon recovering
      a different tree from the one expected based on prior evidence. We demonstrate
      that methods that do not force the data onto a single tree, such as spectral
      analysis, Neighbor-Net, and consensus networks, can be used to detect conflicting
      signals within the data, including those caused by long-branch attraction. We
      illustrate this approach using a set of taxa from three unambiguously
      monophyletic families within the Pelecaniformes: the darters, the cormorants and
      shags, and the gannets and boobies. These three families are universally
      acknowledged as forming a monophyletic group, but the relationship between the
      families remains contentious. Using sequence data from three mitochondrial genes
      (12S, ATPase 6, and ATPase 8) we demonstrate that the relationship between these
      three families is difficult to resolve because they are separated by a short
      internal branch and there are conflicting signals due to long-branch attraction,
      which are confounded with nonhomogeneous sequence evolution across the different
      genes. Spectral analysis, Neighbor-Net, and consensus networks reveal conflicting
      signals regarding the placement of one of the darters, with support found for
      darter monophyly, but also support for a conflicting grouping with the outgroup,
      pelicans. Furthermore, parsimony and maximum-likelihood analyses produced
      different trees, with one of the two most parsimonious trees not supporting the
      monophyly of the darters. Monte Carlo simulations, however, were not sensitive
      enough to reveal long-branch attraction unless the branches are longer than those
      actually observed. These results indicate that spectral analysis, Neighbor-Net,
      and consensus networks offer a powerful approach to detecting and understanding
      the source of conflicting signals within phylogenetic data.

PMID- 16109706
TI  - Patterns of cladogenesis in the venomous marine gastropod genus Conus from the
      Cape Verde islands.
AB  - Isolated oceanic archipelagos are excellent model systems to study speciation,
      biogeography, and evolutionary factors underlying the generation of biological
      diversity. Despite the wealth of studies documenting insular speciation, few of
      them focused on marine organisms. Here, we reconstruct phylogenetic relationships
      among species of the marine venomous gastropod genus Conus from the Cape Verde
      archipelago. This small island chain located in the Central Atlantic hosts 10% of
      the worldwide species diversity of Conus. Analyses were based on mtDNA sequences,
      and a novel nuclear marker, a megalin-like protein, member of the low-density
      lipoprotein receptor gene family. The inferred phylogeny recovered two well
      defined clades within Conus. One includes Cape Verde endemic species with larger
      shells, known as the "venulatus" complex together with C. pulcher from the Canary
      Islands. The other is composed of Cape Verde endemic and West Africa and Canary
      Island "small" shelled species. In both clades, nonendemic Conus were resolved as
      sister groups of the Cape Verde endemics, respectively. Our results indicate that
      the ancestors of "small" and "large" shelled lineages independently colonized
      Cape Verde. The resulting biogeographical pattern shows the grouping of most Cape
      Verde endemics in monophyletic island assemblages. Statistical tests supported a
      recent radiation event within the "small shell" clade. Using a molecular clock,
      we estimated that the colonization of the islands by the "small" shelled species
      occurred relatively close to the origin of the islands whereas the arrival of
      "large" shelled Conus is more recent. Our results suggest that the main factor
      responsible for species diversity in the archipelago may be allopatric speciation
      promoted by the reduced dispersal capacity of nonplanktonic lecithotrophic
      larvae.

PMID- 16109707
TI  - Older people's use of Accident & Emergency services.

PMID- 16109709
TI  - Identification of PamA as a PII-binding membrane protein important in nitrogen
      related and sugar-catabolic gene expression in Synechocystis sp. PCC 6803.
AB  - The PII signaling protein plays a pivotal role in the coordination of carbon and
      nitrogen metabolism in a wide variety of bacteria, Archaea, and plant
      chloroplasts. By using a yeast two-hybrid screening system, we identified a
      transmembrane protein, designated PamA (encoded by sll0985), as a PII-binding
      protein in Synechocystis sp. PCC 6803. The interaction between PII and PamA was
      confirmed in vitro, and the interaction was inhibited in the presence of ATP and
      2-oxoglutarate, whereas the interaction was not influenced by the phosphorylation
      status of PII. Northern blot analyses revealed that the transcripts of a set of
      nitrogen-related genes, including nblA, nrtABCD, and ureG, were decreased in a
      pamA deletion mutant. The mRNA and protein levels of a group 2 sigma factor SigE
      were also reduced by the pamA mutation, and transcripts for sugar catabolic
      genes, such as gap1, zwf, and gnd that are under the control of SigE, were
      consequently decreased in the pamA mutant. In addition, the pamA mutant was found
      to be unable to grow in glucose-containing media. These results indicate that
      PamA has a role in the transcript control of genes for nitrogen and sugar
      metabolism in Synechocystis sp. PCC 6803.

PMID- 16109708
TI  - Microfluidic device for rapid (<15 min) automated microarray hybridization.
AB  - BACKGROUND: Current hybridization protocols on microarrays are slow and need
      skilled personnel. Microfluidics is an emerging science that enables the
      processing of minute volumes of liquids to perform chemical, biochemical, or
      enzymatic analyzes. The merging of microfluidics and microarray technologies
      constitutes an elegant solution that will automate and speed up microarray
      hybridization. METHODS: We developed a microfluidic flow cell consisting of a
      network of chambers and channels molded into a polydimethylsiloxane substrate.
      The substrate was aligned and reversibly bound to the microarray printed on a
      standard glass slide to form a functional microfluidic unit. The microfluidic
      units were placed on an engraved, disc-shaped support fixed on a rotational
      device. Centrifugal forces drove the sample and buffers directly onto the
      microarray surface. RESULTS: This microfluidic system increased the hybridization
      signal by approximately 10fold compared with a passive system that made use of 10
      times more sample. By means of a 15-min automated hybridization process,
      performed at room temperature, we demonstrated the discrimination of 4 clinically
      relevant Staphylococcus species that differ by as little as a single-nucleotide
      polymorphism. This process included hybridization, washing, rinsing, and drying
      steps and did not require any purification of target nucleic acids. This platform
      was sensitive enough to detect 10 PCR-amplified bacterial genomes. CONCLUSION:
      This removable microfluidic system for performing microarray hybridization on
      glass slides is promising for molecular diagnostics and gene profiling.

PMID- 16109710
TI  - Assembly of an RNA-protein complex. Binding of NusB and NusE (S10) proteins to
      boxA RNA nucleates the formation of the antitermination complex involved in
      controlling rRNA transcription in Escherichia coli.
AB  - Analytical ultracentrifugation and fluorescence anisotropy methods have been used
      to measure the equilibrium parameters that control the formation of the core
      subcomplex of NusB and NusE proteins and boxA RNA. This subcomplex, in turn,
      nucleates the assembly of the antitermination complex that is involved in
      controlling the synthesis of ribosomal RNA in Escherichia coli and that also
      participates in forming the N protein-dependent antitermination complex in
      lambdoid phage synthesis. In this study we determined the dissociation constants
      (K(d) values) for the individual binary interactions that participate in the
      assembly of the ternary NusB-NusE-boxA RNA subassembly, and we showed that
      multiple equilibria, involving both specific and nonspecific binding, are
      involved in the assembly pathway of this protein-RNA complex. The measured K(d)
      values were used to model the in vitro assembly reaction and combined with in
      vivo concentration data to simulate the overall control of the assembly of this
      complex in E. coli at two different cellular growth rates. The results showed
      that at both growth rates assembly proceeds via the initial formation of a weak
      but specific NusB-boxA complex, which is then stabilized by NusE binding. We
      showed that NusE also binds nonspecifically to available single-stranded RNA
      sequences and that such nonspecific protein binding to RNA can help to regulate
      crucial interactions in the assembly of the various macromolecular machines of
      gene expression.

PMID- 16109711
TI  - A picrotoxin-specific conformational change in the glycine receptor M2-M3 loop.
AB  - The external loop linking the M2 and M3 transmembrane domains is crucial for
      coupling agonist binding to channel gating in the glycine receptor chloride
      channel (GlyR). A substituted cysteine accessibility scan previously showed that
      glycine activation increased the surface accessibility of 6 contiguous residues
      (Arg271-Lys276) toward the N-terminal end of the homomeric alpha1 GlyR M2-M3
      loop. In the present study we used a similar approach to determine whether the
      allosteric antagonist, picrotoxin, could impose conformational changes to this
      domain that cannot be induced by varying agonist concentrations alone. Picrotoxin
      slowed the reaction rate of a sulfhydryl-containing compound (MTSET) with A272C,
      S273C, and L274C. Before interpreting this as a picrotoxin-specific
      conformational change, it was necessary to eliminate the possibility of steric
      competition between picrotoxin and MTSET. Accordingly, we showed that picrotoxin
      and the structurally unrelated blocker, bilobalide, were both trapped in the
      R271C GlyR in the closed state and that a point mutation to the pore-lining Thr6'
      residue abolished inhibition by both compounds. We also demonstrated that the
      picrotoxin dissociation rate was linearly related to the channel open
      probability. These observations constitute a strong case for picrotoxin binding
      in the pore. We thus conclude that the picrotoxin-specific effects on the M2-M3
      loop are mediated allosterically. This suggests that the M2-M3 loop responds
      differently to the occupation of different binding sites.

PMID- 16109712
TI  - Enhanced ubiquitylation and accelerated degradation of the dopamine transporter
      mediated by protein kinase C.
AB  - Dopamine transporter (DAT) localization in dopaminergic neurons plays an
      important role in regulating dopamine signaling. However, the mechanisms of DAT
      trafficking that control DAT localization are still poorly understood. To gain
      insight into these mechanisms, human DAT was purified in large amounts using a
      two-step affinity chromatography procedure from untreated HeLa cells or cells
      treated with phorbol 12-myristate 13-acetate (PMA). Mass spectrometric analysis
      of purified DAT complexes revealed the presence of several proteins, among which
      ubiquitin was particularly abundant in the PMA-treated sample. Western blotting
      of highly purified DAT protein confirmed constitutive ubiquitylation of DAT and a
      dramatic increase in DAT ubiquitylation in cells treated with PMA. This increase
      was blocked by pretreatment with the protein kinase C (PKC) inhibitor bis
      indolylmaleimide. DAT ubiquitylation by ectopically expressed ubiquitin was
      demonstrated in cells transiently transfected with yellow fluorescent protein
      tagged ubiquitin. In addition, fluorescence resonance energy transfer was
      detected between cyan fluorescent protein-tagged DAT and yellow fluorescent
      protein-tagged ubiquitin, indicative of DAT-ubiquitin conjugation. Interestingly,
      the largest fluorescence resonance energy transfer signals were observed in
      endosomes. Ubiquitylated DAT was detected in the plasma membrane using cell
      surface biotinylation as well as in intracellular compartments, suggesting that
      ubiquitylation begins at the plasma membrane and is maintained in endosomes. In
      both porcine aortic endothelial and HeLa cells, where PKC-dependent DAT
      ubiquitylation was observed, PKC activation resulted in rapid degradation of DAT
      (t12 = 1-2 h). Altogether, these data suggest that PKC-induced DAT ubiquitylation
      may target DAT to lysosomal degradation.

PMID- 16109713
TI  - Apoptosis induced by the kinase inhibitor BAY 43-9006 in human leukemia cells
      involves down-regulation of Mcl-1 through inhibition of translation.
AB  - BAY 43-9006 is a kinase inhibitor that induces apoptosis in a variety of tumor
      cells. Here we report that treatment with BAY 43-9006 results in marked
      cytochrome c and AIF release into the cytosol, caspase-9, -8, -7, and -3
      activation, and apoptosis in human leukemia cells (U937, Jurkat, and K562).
      Pronounced apoptosis was also observed in blasts from patients with acute myeloid
      leukemia. These events were accompanied by ERK1/2 inactivation and caspase
      independent down-regulation of Mcl-1. Inducible expression of a constitutively
      active MEK1 construct did not prevent Mcl-1 down-regulation, suggesting that this
      event is not related to MEK/ERK pathway inactivation. Furthermore, BAY 43-9006
      did not induce major changes in Mcl-1 mRNA levels monitored by real-time PCR or
      Mcl-1 promoter activity demonstrated by luciferase reporter assays, but it did
      enhance Mcl-1 down-regulation in actinomycin D-treated cells. Inhibition of
      protein synthesis by cycloheximide or proteasome function with MG132 and pulse
      chase studies with [35S]methionine demonstrated that BAY 43-9006 did not diminish
      Mcl-1 protein stability, nor did it enhance Mcl-1 ubiquitination, but instead
      markedly attenuated Mcl-1 translation in association with the rapid and potent
      dephosphorylation of the eIF4E translation initiation factor. Finally, ectopic
      expression of Mcl-1 in leukemic cells markedly inhibited BAY 43-9006-mediated
      cytochrome c cytosolic release, caspase-9, -7, and -3 activation, as well as cell
      death, indicating that Mcl-1 operates upstream of cytochrome c release and
      caspase activation. Together, these findings demonstrate that BAY 43-9006
      mediates cell death in human leukemia cells, at least in part, through down
      regulation of Mcl-1 via inhibition of translation.

PMID- 16109714
TI  - Nuclear factor of activated T cells c1 induces osteoclast-associated receptor
      gene expression during tumor necrosis factor-related activation-induced cytokine
      mediated osteoclastogenesis.
AB  - Osteoclast differentiation from hematopoietic precursors is controlled by the
      tumor necrosis factor family member tumor necrosis factor-related activation
      induced cytokine (TRANCE) via induction of various transcription factors,
      including nuclear factor of activated T cells (NFAT) c1. During osteoclast
      differentiation, NFATc1 is further activated via calcium signaling when
      costimulatory receptors expressed on osteoclast precursors, such as osteoclast
      associated receptor (OSCAR), are stimulated. Here we show that NFATc1 expression
      precedes that of OSCAR during TRANCE-mediated osteoclastogenesis and that
      inhibition of NFATc1 by cyclosporin A abolishes TRANCE-induced OSCAR expression
      and subsequent osteoclast differentiation. Moreover, we show that the 1.0-kb
      promoter region of the OSCAR gene contains three potential NFATc1-binding sites.
      Induction of an OSCAR promoter-luciferase reporter is significantly increased
      when transiently transfected into 293T cells in combination with NFATc1
      expression plasmid. Deletion and site-directed mutant constructs confirmed that
      NFATc1-binding sites are both functional and NFATc1-specific. Furthermore, NFATc1
      synergistically activates an OSCAR reporter construct together with
      microphthalmia transcription factor and PU.1, transcription factors previously
      shown to be critical for osteoclast differentiation. In addition, a plasmid
      expressing constitutively active MAP kinase kinase 6 enhances the transactivation
      activity of NFATc1/microphthalmia transcription factor/PU.1 on the OSCAR
      promoter. Taken together, our results indicate that NFATc1 is an important
      transcription factor in the induction of OSCAR during osteoclastogenesis.
      Elucidation of NFATc1 as a transcription factor for OSCAR expression implies the
      presence of a positive feedback circuit of TRANCE-induced activation of NFATc1,
      involving NFATc1-mediated OSCAR expression and its subsequent activation of
      NFATc1, necessary for efficient differentiation of osteoclasts.

PMID- 16109715
TI  - Involvement of endogenous bone morphogenetic protein (BMP) 2 and BMP6 in bone
      formation.
AB  - Although accumulated evidence has shown the bone anabolic effects of bone
      morphogenetic proteins (BMPs) that were exogenously applied in vitro and in vivo,
      the roles of endogenous BMPs during bone formation remain to be clarified. This
      study initially investigated expression patterns of BMPs in the mouse long bone
      and found that BMP2 and BMP6 were the main subtypes expressed in hypertrophic
      chondrocytes that induce endochondral bone formation. We then examined the
      involvement of the combination of these BMPs in bone formation in vivo by
      generating the compound-deficient mice (Bmp2+/-;Bmp6-/-). Under physiological
      conditions, these mice exhibited moderate growth retardation compared with the
      wild-type (WT) littermates during the observation period up to 52 weeks of age.
      Both the fetal and adult compound-deficient mice showed a reduction in the
      trabecular bone volume with suppressed bone formation, but normal bone
      resorption, whereas the single deficient mice (Bmp2+/- or Bmp6-/-) did not. When
      a fracture was created at the femoral midshaft and the bone healing was analyzed,
      the endochondral bone formation, but not intramembranous bone formation, was
      impaired by the compound deficiency. In the cultures of bone marrow cells,
      however, there was no difference in osteogenic differentiation between WT and
      compound-deficient cells in the presence or absence of the exogenous BMP2. We
      thus concluded that endogenous BMP2 and BMP6 cooperatively play pivotal roles in
      bone formation under both physiological and pathological conditions.

PMID- 16109716
TI  - mTOR-dependent suppression of protein phosphatase 2A is critical for
      phospholipase D survival signals in human breast cancer cells.
AB  - A critical aspect of tumor progression is the generation of survival signals that
      overcome default apoptotic programs. Recent studies have revealed that elevated
      phospholipase D activity generates survival signals in breast and perhaps other
      human cancers. We report here that the elevated phospholipase D activity in the
      human breast cancer cell line MDA-MB-231 suppresses the activity of the putative
      tumor suppressor protein phosphatase 2A in a mammalian target of rapamycin (mTOR)
      dependent manner. Increasing the phospholipase D activity in MCF7 cells also
      suppressed protein phosphatase 2A activity. Elevated phospholipase D activity
      suppressed association of protein phosphatase 2A with both ribosomal subunit S6
      kinase and eukaryotic initiation factor 4E-binding protein 1. Suppression of
      protein phosphatase 2A by SV40 small t-antigen has been reported to be critical
      for the transformation of human cells with SV40 early region genes. Consistent
      with a critical role for protein phosphatase 2A in phospholipase D survival
      signals, either SV40 small t-antigen or pharmacological suppression of protein
      phosphatase 2A restored survival signals lost by the suppression of either
      phospholipase D or mTOR. Blocking phospholipase D signals also led to reduced
      phosphorylation of the pro-apoptotic protein BAD at the protein phosphatase 2A
      dephosphorylation site at Ser-112. The ability of phospholipase D to suppress
      protein phosphatase 2A identifies a critical target of an emerging phospholipase
      D/mTOR survival pathway in the transformation of human cells.

PMID- 16109717
TI  - Sox9 and p300 cooperatively regulate chromatin-mediated transcription.
AB  - Chromatin structure is a fundamental component of gene regulation, expression,
      and cellular differentiation. We have previously reported that the
      multifunctional coactivator p300 is a member of the Sox9 (Sry-type high mobility
      group box 9)-related transcriptional apparatus and activates Sox9-dependent
      transcription during chondrogenesis. However, the mechanism of synergy between
      Sox9 and p300 in chromatin-mediated transcription has not been elucidated. In the
      present study we investigated the activity of Sox9 and p300 on chromatinized
      templates in vitro. Recombinant Sox9 was shown to be associated with several
      transcriptional cofactors including p300. In vitro transcription assays revealed
      that p300 potentiated Sox9-dependent transcription on chromatinized DNA and,
      importantly, was associated with hyperacetylated histones. Consistent with these
      results, the histone deacetylase inhibitor trichostatin A stimulated the
      expression of Sox9-regulated cartilage matrix genes and induced histone
      acetylation around the enhancer region of the collagen alpha1 (II) gene in
      chondrocytes. These findings suggest that Sox9 interacts with chromatin and
      activates transcription via regulation of chromatin modification.

PMID- 16109719
TI  - Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and
      non-genomic regulation of lipogenic and oxidative pathways.
AB  - Menopause is associated with increased adiposity and greater risk of metabolic
      disease. In the ovariectomized (OVX) rodent model of menopause, increased
      adiposity is prevented by estrogen (E2) replacement, reflecting both anorexigenic
      and potentially metabolic actions of E2. To elucidate metabolic and molecular
      mechanisms by which E2 regulates fat storage and fat mobilization independently
      of reduced energy intake, C57 BL/6 mice were ovariectomized, randomized to
      estrogen (OVX-E2) or control pellet implants (OVX-C), and pairfed for 40 days. E2
      treatment was associated with reduced adipose mass and adipocyte size and down
      regulation of lipogenic genes in adipocytes under the control of sterol
      regulatory element-binding protein 1c. Adipocytes of OVX-E2 mice contained >3
      fold more perilipin protein than adipocytes of pairfed control (OVX) mice, and
      this difference was associated with enhanced ex vivo lipolytic response to
      catecholamines and with greater levels of serum-free fatty acids following
      fasting. As in adipose tissue, E2 decreased the expression of lipogenic genes in
      liver and skeletal muscle. In the latter, E2 appears to promote the partitioning
      of free fatty acids toward oxidation and away from triglyceride storage by up
      regulating the expression of peroxisome proliferation activator receptor-delta
      and its downstream targets and also by directly and rapidly activating AMP
      activated protein kinase. Thus, novel genomic and non-genomic actions of E2
      promote leanness in OVX mice independently of reduced energy intake.

PMID- 16109718
TI  - Interaction of RNA-binding proteins HuR and AUF1 with the human ATF3 mRNA 3'
      untranslated region regulates its amino acid limitation-induced stabilization.
AB  - ATF3 expression is induced in cells exposed to a variety of stress conditions,
      including nutrient limitation. Here we demonstrated that the mechanism by which
      the ATF3 mRNA content is increased following amino acid limitation of human HepG2
      hepatoma cells is mRNA stabilization. Analysis of ATF3 mRNA turnover revealed
      that the half-life was increased from about 1 h in control cells to greater than
      8 h in the histidine-deprived state, demonstrating mRNA stabilization in response
      to nutrient deprivation. Treatment of HepG2 cells with thapsigargin, which causes
      endoplasmic reticulum stress, also increased the half-life of ATF3 mRNA. HuR is
      an RNA-binding protein that regulates both the stability and cytoplasmic/nuclear
      localization of mRNA species containing AU-rich elements. Another RNA-binding
      protein, AUF1, regulates target mRNA molecules by enhancing their decay. Amino
      acid limitation caused a slightly elevated mRNA level for HuR and AUF1 mRNA. The
      nuclear HuR protein content was unchanged, and AUF1 protein increased slightly
      after amino acid limitation, whereas the cytoplasmic levels of both HuR and AUF1
      protein increased. Immunoprecipitation of HuR-RNA complexes followed by reverse
      transcriptase-PCR analysis showed that HuR interacted with ATF3 mRNA in vivo and
      that this interaction increased following amino acid limitation. In contrast, the
      interaction of AUF1 with the ATF3 mRNA is decreased in histidine-deprived cells
      relative to control cells. Suppression of HuR expression by RNA interference
      partially blocked the accumulation of ATF3 mRNA following amino acid deprivation.
      The results demonstrated that coordinated regulation of mRNA stability by HuR and
      AUF1 proteins contributes to the observed increase in ATF3 expression following
      amino acid limitation.

PMID- 16109720
TI  - Dpp-responsive silencers are bound by a trimeric Mad-Medea complex.
AB  - Transcriptional regulation by transforming growth factor-beta signaling is
      mediated by the Smad family of transcription factors. It is generally accepted
      that Smads must interact with other transcription factors to bind to their
      targets. However, recently it has been shown that a complex of the Drosophila
      Smad proteins, Mad and Medea, binds with high affinity to silencer elements that
      repress brinker and bag of marbles in response to Dpp signaling. Here we report
      that these silencers are bound by a heterotrimer containing two Mad subunits and
      one Medea subunit. We found that the MH1 domains of all three subunits
      contributed directly to sequence-specific DNA contact, thus accounting for the
      exceptionally high stability of the Smad-silencer complex. The Medea MH1 domain
      binds to a canonical Smad box (GTCT), whereas the Mad MH1 domains bind to a GC
      rich sequence resembling Mad binding sites previously identified in Dpp
      responsive enhancer elements. The consensus for this sequence, GRCGNC, differs
      from that of the canonical Smad box, but we found that Mad binding nonetheless
      required the same beta-hairpin amino acids that mediate base-specific contact
      with GTCT. Binding was also affected by alanine substitutions in Mad and Med at a
      subset of basic residues within and flanking helix 2, indicating a contribution
      to binding of the GRCGNC and GTCT sites. The slight alteration of the Dpp
      silencers caused them to activate transcription in response to Dpp signaling,
      indicating that the potential for Smad complexes to recognize specific targets
      need not be limited to repression.

PMID- 16109721
TI  - Yeast PIAS-type Ull1/Siz1 is composed of SUMO ligase and regulatory domains.
AB  - SUMO (small ubiquitin-like modifier)/Smt3 (suppressor of mif two) is a member of
      the ubiquitin-related protein family and is known to conjugate with many
      proteins. In the sumoylation pathway, SUMO/Smt3 is transferred to substrate
      lysine residues through the thioester cascade of E1 (activating enzyme) and E2
      (conjugating enzyme), and E3 (SUMO ligase) functions as an adaptor between E2 and
      each substrate. Yeast Ull1 (ubiquitin-like protein ligase 1)/Siz1, a PIAS
      (protein inhibitor of activated STAT)-type SUMO ligase, modifies both cytoplasmic
      and nuclear proteins. In this paper, we performed a domain analysis of Ull1/Siz1
      by constructing various deletion mutants. A novel conserved N-terminal domain,
      called PINIT, as well as the RING-like domain (SP-RING) were required for the
      SUMO ligase activity in the in vitro conjugation system and for interaction with
      Smt3 in an in vitro binding assay. The most distal N-terminal region, which
      contains a putative DNA-binding SAF-A/B, Acinus, and PIAS (SAP) motif, was not
      required for the ligase activity but was involved in nuclear localization. A
      strong SUMO-binding motif was identified, which interacted with Smt3 in the two
      hybrid system but was not necessary for the ligase activity. The most distal C
      terminal domain was important for stable localization at the bud neck region and
      thereby for the substrate recognition of septins. Furthermore, the C-terminal
      half conferred protein instability on Ull1/Siz1. Taken together, we conclude that
      the SP-RING and PINIT of Ull1/Siz1 are core domains of the SUMO ligase, and the
      other domains are regulatory for protein stability and subcellular localization.

PMID- 16109722
TI  - The conformationally dynamic C helix of the RIalpha subunit of protein kinase A
      mediates isoform-specific domain reorganization upon C subunit binding.
AB  - Different isoforms of the full-length protein kinase A (PKA) regulatory subunit
      homodimer (R2) and the catalytic (C) subunit-bound holoenzyme (R2C2) have very
      different global structures despite similar molecular weights and domain
      organization within their primary sequences. To date, it has been the linker
      sequence between the R subunit dimerization/docking domain and cAMP-binding
      domain A that has been implicated in modulating domain interactions to give rise
      to these differences in global structure. The small angle solution scattering
      data presented here for three different isoforms of PKA heterodimer (deltaR-C)
      complexes reveal a role for another conformationally dynamic sequence in
      modulating inter-subunit and domain interactions, the C helix that connects the
      cAMP-binding domains A and B of the R subunit. The deltaR-C heterodimer complexes
      studied here were each formed with a monomeric N-terminal deletion mutant of the
      R subunit (deltaR) that contains the inhibitor sequence and both cAMP-binding
      domains. The scattering data show that type IIalpha and type IIbeta deltaR-C
      heterodimers are relatively compact and globular, with the C subunit contacting
      the inhibitor sequence and both cAMP-binding domains. In contrast, the type
      Ialpha heterodimer is significantly more extended, with the C subunit interacting
      with the inhibitor sequence and cAMP-binding domain A, whereas domain B extends
      out such that its surface is almost completely solvent exposed. These data
      implicate the C helix of RIalpha in modulating isoform-specific interdomain
      communication in the PKA holoenzyme, adding another layer of structural
      complexity to our understanding of signaling dynamics in this multisubunit,
      multidomain protein kinase.

PMID- 16109723
TI  - Proprotein convertases [corrected] are responsible for proteolysis and
      inactivation of endothelial lipase.
AB  - Plasma lipoprotein metabolism is tightly regulated by several members of the
      triglyceride lipase family, including endothelial lipase (EL) and lipoprotein
      lipase (LPL). Our previous work suggested that EL is proteolytically processed.
      In this report, we have used a combination of epitope tagging, mutagenesis, and N
      terminal sequencing to determine the precise location of the cleavage site within
      EL. The cleavage occurs immediately after the sequence RNKR, a known recognition
      sequence for the proprotein convertase (PC) family. We demonstrate that some PCs,
      but not all, can proteolytically cleave EL at this site and thereby directly
      regulate EL enzymatic activity through modulating EL cleavage. Furthermore,
      specific knockdown of individual PCs proves that PCs are the proteases that
      cleave EL in human endothelial cells. Interestingly, a homologous site in LPL is
      also cleaved by PCs. This action is unusual for PCs, which are traditionally
      known as activators of pro-proteins, and highlights a potential role of PCs in
      lipid metabolism through their proteolytic processing of lipases.

PMID- 16109724
TI  - Activation of olfactory cyclic-nucleotide gated channels revisited.

PMID- 16109725
TI  - Mitral annular myocardial velocity assessment of segmental left ventricular
      diastolic function after prolonged exercise in humans.
AB  - We assessed segmental and global left ventricular (LV) diastolic function via
      tissue-Doppler imaging (TDI) as well as Doppler flow variables before and after a
      marathon race to extend our knowledge of exercise-induced changes in cardiac
      function. Twenty-nine subjects (age 18-62 year) volunteered to participate and
      were assessed pre- and post-race. Measurements of longitudinal plane TDI
      myocardial diastolic velocities at five sites on the mitral annulus included peak
      early myocardial tissue velocity (E'), peak late (or atrial) myocardial tissue
      velocity (A') and the ratio E'/A'. Standard pulsed-wave Doppler transmitral and
      pulmonary vein flow indices were also recorded along with measurements of body
      mass, heart rate, blood pressures and cardiac troponin T (cTnT), a biomarker of
      myocyte damage. Pre- to post-race changes in LV diastolic function were analysed
      by repeated measures ANOVA. Delta scores for LV diastolic function were
      correlated with each other and alterations in indices of LV loading. Diastolic
      longitudinal segmental and mean TDI data were altered post-race such that the
      mean E'/A' ratio was significantly depressed (1.51 +/- 0.34 to 1.16 +/- 0.35, P <
      0.05). Changes in segmental and global TDI data were not related to an elevated
      post-race HR, a decreased post-race pre-load or an elevated cTnT. The pulsed wave
      Doppler ratio of peak early transmitral flow velocity (E)/peak late (or atrial)
      flow velocity (A) was also significantly reduced post-race (1.75 +/- 0.46 to 1.05
      +/- 0.30, P < 0.05); however, it was significantly correlated with post-race
      changes in heart rate. The lack of change in E/E' from pre- to post-race (3.4 +/-
      0.8 and 3.3 +/- 0.7, respectively) suggests that the depression in diastolic
      function is likely to be due to altered relaxation of the left ventricle;
      however, the exact aetiology of this change remains to be determined.

PMID- 16109726
TI  - Cl- secretion in ATP-treated renal epithelial C7-MDCK cells is mediated by
      activation of P 2Y1 receptors, phospholipase A2 and protein kinase A.
AB  - This study examines the mechanism of P 2Y-induced Cl- secretion in monolayers of
      C7-Madin-Darby canine kidney (MDCK) cells triggered by basolateral application of
      ATP and measured as transcellular short current (I(SC)). Both ATP-induced
      arachidonic acid (AA) synthesis and I(SC) in ATP-treated cells were abolished by
      the phosholipase A2 (PLA2) inhibitor, AACOCF3. The cyclo-oxygenase inhibitor
      indomethacin decreased I(SC) and cAMP production in ATP-treated cells with an
      IC50 of approximately 0.3 microm. ATP led to rapid activation of cAMP-dependent
      protein kinase A (PKA), as estimated by phosphorylation of a vasodilator
      stimulated phosphoprotein. PKA activity and I(SC) evoked by ATP, as well as by
      prostaglandin E1 (PGE1), were diminished in the presence of the PKA inhibitor H
      89 or an adenovirus-mediated expression of PKA-inhibitor protein, PKI. In
      contrast, indomethacin completely blocked the increment of PKA and I(SC)
      triggered by ATP and AA, but did not affect PKA activation and I(SC) detected
      with PGE1. The kinetics of [Ca2+]i elevation in ATP- and thapsigargin-treated
      cells were similar and suppressed by the Ca(2+)i chelator BAPTA. Neither baseline
      nor maximal increment of ATP-induced I(SC) was affected by thapsigargin and
      BAPTA. Real-time PCR showed that C7 cells express more mRNA for P 2Y1 and P 2Y2
      than for other P 2Y receptor subtypes. The rank order of potency (2MeSATP > ATP >
      ADP >> UTP) indicates that P 2Y1 rather than P 2Y2 receptors contribute to PKA
      and I(SC) activation. Viewed collectively, these data show that Cl- secretion in
      C7-MDCK monolayers treated with basolateral ATP is triggered by P 2Y1 receptors
      and is mediated by subsequent [Ca2+]i-independent activation of PLA2 and PKA.

PMID- 16109727
TI  - Interaction of chemoreceptor and baroreceptor reflexes by hypoxia and hypercapnia
      - a mechanism for promoting hypertension in obstructive sleep apnoea.
AB  - Asphyxia, which occurs during obstructive sleep apnoeic events, alters the
      baroreceptor reflex and this may lead to hypertension. We have recently reported
      that breathing an asphyxic gas resets the baroreceptor-vascular resistance reflex
      towards higher pressures. The present study was designed to determine whether
      this effect was caused by the reduced oxygen tension, which affects mainly
      peripheral chemoreceptors, or by the increased carbon dioxide, which acts mainly
      on central chemoreceptors. We studied 11 healthy volunteer subjects aged between
      20 and 55 years old (6 male). The stimulus to the carotid baroreceptors was
      changed using graded pressures of -40 to +60 mmHg applied to a neck chamber.
      Responses of vascular resistance were assessed in the forearm from changes in
      blood pressure (Finapres) divided by brachial blood flow velocity (Doppler) and
      cardiac responses from the changes in RR interval and heart rate. Stimulus
      response curves were defined during (i) air breathing, (ii) hypoxia (12% O(2) in
      N(2)), and (iii) hypercapnia (5% CO(2) in 95% O(2)). Responses during air
      breathing were assessed both prior to and after either hypoxia or hypercapnia. We
      applied a sigmoid function or third order polynomial to the curves and determined
      the maximal differential (equivalent to peak sensitivity) and the corresponding
      carotid sinus pressure (equivalent to 'set point'). Hypoxia resulted in an
      increase in heart rate but no significant change in mean blood pressure or
      vascular resistance. However, there was an increase in vascular resistance in the
      post-stimulus period. Hypoxia had no significant effect on baroreflex sensitivity
      or 'set point' for the control of RR interval, heart rate or mean arterial
      pressure. Peak sensitivity of the vascular resistance response to baroreceptor
      stimulation was significantly reduced from -2.5 +/- 0.4 units to -1.4 +/- 0.1
      units (P < 0.05) and this was restored in the post-stimulus period to -2.6 +/-
      0.5 units. There was no effect on 'set point'. Hypercapnia, on the other hand,
      resulted in a decrease in heart rate, which remained reduced in the post-stimulus
      period and significantly increased mean blood pressure. Baseline vascular
      resistance was significantly increased and then further increased in the post
      control period. Like hypoxia, hypercapnia had no effect on baroreflex control of
      RR interval, heart rate or mean arterial pressure. There was, also no significant
      change in the sensitivity of the vascular resistance responses, however, 'set
      point' was significantly increased from 74.7 +/- 4 to 87.0 +/- 2 mmHg (P < 0.02).
      This was not completely restored to pre-stimulus control levels in the post
      stimulus control period (82.2 +/- 3 mmHg). These results suggest that the hypoxic
      component of asphyxia reduces baroreceptor-vascular resistance reflex
      sensitivity, whilst the hypercapnic component is responsible for increasing blood
      pressure and reflex 'set point'. Hypercapnia appears to have a lasting effect
      after the removal of the stimulus. Thus the effect of both peripheral and central
      chemoreceptors on baroreflex function may contribute to promoting hypertension in
      patients with obstructive sleep apnoea.

PMID- 16109729
TI  - Induction and maintenance of late-phase long-term potentiation in isolated
      dendrites of rat hippocampal CA1 pyramidal neurones.
AB  - Expression of N-methyl-d-aspartate (NMDA) receptor-dependent long-term
      potentiation (LTP) in the CA1 region of the hippocampus can be divided into an
      early (1-2 h), protein synthesis-independent phase and a late (>4 h), protein
      synthesis-dependent phase. In this study we have addressed whether the de novo
      protein synthesis required for the expression of late-LTP can be sustained solely
      from the translation of mRNAs located in the dendrites of CA1 pyramidal neurones.
      Our results show that late-LTP, lasting at least 5 h, can be maintained in
      hippocampal slices where the dendrites located in stratum radiatum have been
      isolated from their cell bodies by a microsurgical cut. The magnitude of the
      potentiation of the slope of field EPSPs in these 'isolated' slices was similar
      to that recorded in 'intact' slices. Incubation of the slices with the mRNA
      translation inhibitor cycloheximide or the mammalian target of rapamycin (mTOR)
      inhibitor rapamycin blocked late-LTP in both 'intact' and 'isolated' slice
      preparations. In contrast, incubation of slices with the transcription inhibitor,
      actinomycin D, resulted in a reduction of sustained potentiation, at 4 h, in
      'intact' slices while in 'isolated' slices the magnitude of potentiation was
      similar to that seen in untreated slices. These results indicate that late-LTP
      can be induced and maintained in 'isolated' dendritic preparations via
      translation of pre-existing mRNAs.

PMID- 16109728
TI  - Mechanisms of target-cell specific short-term plasticity at Schaffer collateral
      synapses onto interneurones versus pyramidal cells in juvenile rats.
AB  - Although it is presynaptic, short-term plasticity has been shown at some synapses
      to depend upon the postsynaptic cell type. Previous studies have reported
      conflicting results as to whether Schaffer collateral axons have target-cell
      specific short-term plasticity. Here we investigate in detail the short-term
      dynamics of Schaffer collateral excitatory synapses onto CA1 stratum radiatum
      interneurones versus pyramidal cells in acute hippocampal slices from juvenile
      rats. In response to three stimulus protocols that invoke different forms of
      short-term plasticity, we find differences in some but not all forms of
      presynaptic short-term plasticity, and heterogeneity in the short term plasticity
      of synapses onto interneurones. Excitatory synapses onto the majority of
      interneurones had less paired-pulse facilitation than synapses onto pyramidal
      cells across a range of interpulse intervals (20-200 ms). Unlike synapses onto
      pyramidal cells, synapses onto most interneurones had very little facilitation in
      response to short high-frequency trains of five pulses at 5, 10 and 20 Hz, and
      depressed during trains at 50 Hz. However, the amount of high-frequency
      depression was not different between synapses onto pyramidal cells versus the
      majority of interneurones at steady state during 2-10 Hz trains. In addition, a
      small subset of interneurones (approximately 15%) had paired-pulse depression
      rather than paired-pulse facilitation, showed only depression in response to the
      high-frequency five pulse trains, and had more steady-state high-frequency
      depression than synapses onto pyramidal cells or the majority of interneurones.
      To investigate possible mechanisms for these differences in short-term
      plasticity, we developed a mechanistic mathematical model of neurotransmitter
      release that explicitly explores the contributions to different forms of short
      term plasticity of the readily releasable vesicle pool size, release probability
      per vesicle, calcium-dependent facilitation, synapse inactivation following
      release, and calcium-dependent recovery from inactivation. Our model fits the
      responses of each of the three cell groups to the three different stimulus
      protocols with only two parameters that differ with cell group. The model
      predicts that the differences in short-term plasticity between synapses onto CA1
      pyramidal cells and stratum radiatum interneurones are due to a higher initial
      release probability per vesicle and larger readily releasable vesicle pool size
      at synapses onto interneurones, resulting in a higher initial release
      probability. By measuring the rate of block of NMDA receptors by the open channel
      blocker MK-801, we confirmed that the initial release probability is greater at
      synapses onto interneurones versus pyramidal cells. This provides a mechanism by
      which both the initial strength and the short-term dynamics of Schaffer
      collateral excitatory synapses are regulated by their postsynaptic target cell.

PMID- 16109730
TI  - Muscle spindle signals combine with the sense of effort to indicate limb
      position.
AB  - Experiments were carried out to test the hypothesis that, in the absence of
      vision, position sense at the human forearm is generated by the combined input
      from muscle spindles in elbow flexor muscles and signals of central origin giving
      rise to a sense of effort. In a forearm position-matching task, to remove a
      possible contribution from the sense of effort, the reference arm was held
      supported at the test angle. Subjects were less accurate in matching elbow
      position of the supported forearm than when it was unsupported. Adding a 2 kg
      weight to the unsupported reference arm led subjects to make matching errors
      consistent with an increase in the effort signal. Evidence of a contribution from
      muscle spindles was provided by showing that the direction of position matching
      errors could be systematically altered by flexion or extension conditioning of
      the reference arm before its placement at the test angle. Such changes in errors
      with conditioning could be shown to be present when the reference arm was
      supported, unsupported, or unsupported and weighted. It is concluded that both
      peripheral signals from muscle spindles and signals of central origin, associated
      with the motor command required to maintain arm position against the force of
      gravity, can provide information about forearm position.

PMID- 16109732
TI  - When premature is not premature--the ASCOT study.

PMID- 16109731
TI  - A difference in inward rectification and polyamine block and permeation between
      the Kir2.1 and Kir3.1/Kir3.4 K+ channels.
AB  - Inward rectification is caused by voltage-dependent block of the channel pore by
      intracellular Mg2+ and polyamines such as spermine. In the present study, we
      compared inward rectification in the Kir3.1/Kir3.4 channel, which underlies the
      cardiac current I(K,ACh), and the Kir2.1 channel, which underlies the cardiac
      current I(K,1). Sustained outward current at potentials positive to the K+
      reversal potential was observed through Kir3.1/Kir3.4, but not Kir2.1,
      demonstrating that Kir3.1/Kir3.4 exhibits weaker inward rectification than
      Kir2.1. We show that Kir3.1/Kir3.4 is more sensitive to extracellular spermine
      block than Kir2.1, and that intracellular and extracellular polyamines can
      permeate Kir3.1/Kir3.4, but not Kir2.1, to a limited extent. We describe a simple
      kinetic model in which polyamines act as permeant blockers of Kir3.1/Kir3.4, but
      as relatively impermeant blockers of Kir2.1. The model shows the difference in
      sensitivity to extracellular spermine block, as well as the difference in the
      extent of inward rectification between the two channels. This suggests that
      Kir3.1/Kir3.4 exhibits weaker inward rectification than Kir2.1 because of the
      difference in the balance of polyamine block and permeation of the two channels.

PMID- 16109733
TI  - The contribution of smoking to inequalities in mortality by education varies over
      time and by sex: two national cohort studies, 1981-84 and 1996-99.
AB  - BACKGROUND: The contributions of tobacco smoking to overall mortality and
      socioeconomic inequalities in mortality vary between populations and over time.
      We determined how these contributions varied by sex and over time in two national
      New Zealand cohort studies. METHODS: Poisson regression and modelling were
      conducted on linked census-mortality cohorts for people aged 45-74 years in 1981
      84 and 1996-99 (2.0 and 2.7 million person-years, respectively). RESULTS:
      Contribution to socioeconomic inequalities in mortality. Adjusting for current
      and former smoking reduced the all-cause mortality rate ratios for men with nil
      educational qualifications compared with men with post-school qualifications from
      1.34 to 1.29 in 1981-84 and from 1.31 to 1.25 in 1996-99, or 16 and 21%
      reductions in relative inequalities. Equivalent results for women were 1.42-1.41
      in 1981-84 and 1.42-1.37 in 1996-99, or 3 and 11% reductions in relative
      inequalities. Contribution to overall mortality. Using 1996-99 data, we estimated
      that if all current smokers quit and became ex-smokers, mortality rates would
      reduce by 11% for men and 5% for women. If everyone was a never smoker (i.e. a
      historically smoke-free society), mortality rates would have been 26% lower for
      men and 25% lower for women. CONCLUSIONS: The contribution of smoking to
      educational inequalities in mortality was greater for males, and increased over
      time for both males and females, reflecting the historically differential phasing
      of the tobacco epidemic by sex and socioeconomic position. Complete cessation of
      smoking in contemporary New Zealand would reduce both overall mortality and
      educational inequalities in mortality.

PMID- 16109734
TI  - The contribution of parental and community ethnicity to breastfeeding practices:
      evidence from the Millennium Cohort Study.
AB  - BACKGROUND: The association of ethnic and social factors at the individual and
      community level with inequalities in starting, and continuing, to breastfeed
      remains unclear. We explored these factors using data from the Millennium Cohort
      Study. METHODS: We obtained data for 11 286 natural mothers [8207 (85%) white] of
      singleton infants, living in England at age 9 months. Breastfeeding mothers were
      defined as the proportion of all mothers who reported: putting their baby to the
      breast at least once and giving any breastmilk (initiation); and having started,
      continuing for at least 1 month (continuation). RESULTS: In England, 72% of all
      mothers started breastfeeding, and of these 70% continued for at least 1 month.
      White mothers were the least likely to start breastfeeding (70%), as were
      multiparous mothers (69%), younger mothers, those with no academic qualifications
      (51%), in routine occupations (59%), or living in disadvantaged communities
      (60%). For white mothers, having a partner of a different ethnic group was
      independently and positively associated with breastfeeding initiation and
      continuation to 1 month [adjusted rate ratios (95% CI): 1.14 (1.07-1.21) and 1.09
      (1.03-1.16), respectively]. White lone mothers were more likely to initiate
      breastfeeding if they lived in high ethnic minority communities [adjusted rate
      ratio (95% CI): 1.42 (1.15-1.76)] rather than disadvantaged areas. For all
      mothers, maternal age at first motherhood was positively associated with
      breastfeeding [adjusted rate ratio (95% CI): 1.06 (1.04-1.08) per 5 year
      increase]. CONCLUSIONS: Significant inequalities in breastfeeding practices
      remain within the UK. White women are less likely to breastfeed and, for these
      women, partner and community ethnicity have an important relation to starting and
      continuing to breastfeed. Our findings suggest that public health strategies to
      increase breastfeeding need to be focussed on mothers who are young at first
      motherhood and address support offered by partners and the communities in which
      women live. Measures to evaluate the effectiveness of these strategies over time
      and between places should take account of changes in ethnic composition of the
      child-bearing population.

PMID- 16109735
TI  - Growth dynamics of mechanically impeded lupin roots: does altered morphology
      induce hypoxia?
AB  - BACKGROUND AND AIMS: Root axes elongate slowly and swell radially under
      mechanical impedance. However, temporal and spatial changes to impeded root
      apices have only been described qualitatively. This paper aims (a) to quantify
      morphological changes to root apices and (b) assess whether these changes pre
      dispose young root tissues to hypoxia. METHODS: Lupin (Lupinus angustifolius)
      seedlings were grown into coarse sand that was pressurized through a diaphragm to
      generate mechanical impedance on growing root axes. In situ observations yielded
      growth rates and root response to hypoxia. Roots were then removed to assess
      morphology, cell lengths and local growth velocities. Oxygen uptake into excised
      segments was measured. KEY RESULTS: An applied pressure of 15 kPa slowed root
      extension by 75% after 10-20 h while the same axes thickened by about 50%. The
      most terminal 2-3 mm of axes did not respond morphologically to impedance, in
      spite of the slower flux of cells out of this region. The basal boundary of root
      extension encroached to within 4 mm of the apex (cf. 10 mm in unimpeded roots),
      while radial swelling extended 10 mm behind the apex in impeded roots. Oxygen
      demand by segments of these short, thick, impeded roots was significantly
      different from segments of unimpeded roots when the zones of elongation in each
      treatment were compared. Specifically, impeded roots consumed O2 faster and O2
      consumption was more likely to be O2-limited over a substantial proportion of the
      elongation zone, making these roots more susceptible to O2 deficit. Impeded roots
      used more O2 per unit growth (measured as either unit of elongation or unit of
      volumetric expansion) than unimpeded roots. Extension of impeded roots in situ
      was O2-limited at sub-atmospheric O2 levels (21% O2), while unimpeded roots were
      only limited below 11% O2. CONCLUSIONS: The shift in the zone of extension
      towards the apex in impeded roots coincided with greater vulnerability to hypoxia
      even after soil was removed. Roots still encased in impeded soil are likely to
      suffer from marked O2 deficits.

PMID- 16109736
TI  - Adrenocorticotropic hormone-mediated signaling cascades coordinate a cyclic
      pattern of steroidogenic factor 1-dependent transcriptional activation.
AB  - Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that has emerged as a
      critical mediator of endocrine function at multiple levels of the hypothalamic
      pituitary-steroidogenic axis. Within the adrenal cortex, ACTH-dependent
      transcriptional responses, including transcriptional activation of several key
      steroidogenic enzymes within the steroid biosynthetic pathway, are largely
      dependent upon SF-1 action. The absence of a bona fide endogenous eukaryotic
      ligand for SF-1 suggests that signaling pathway activation downstream of the
      melanocortin 2 receptor (Mc2r) modulates this transcriptional response. We have
      used the chromatin immunoprecipitation assay to examine the temporal formation of
      ACTH-dependent transcription complexes on the Mc2r gene promoter. In parallel,
      ACTH-dependent signaling events were examined in an attempt to correlate
      transcriptional events with the upstream activation of signaling pathways. Our
      results demonstrate that ACTH-dependent signaling cascades modulate the temporal
      dynamics of SF-1-dependent complex assembly on the Mc2r promoter. Strikingly, the
      pattern of SF-1 recruitment and the subsequent attainment of active rounds of
      transcription support a kinetic model of SF-1 transcriptional activation, a model
      originally established in the context of ligand-dependent transcription by
      several classical nuclear hormone receptors. An assessment of the major ACTH
      dependent signaling pathways highlights pivotal roles for the MAPK as well as the
      cAMP-dependent protein kinase A pathway in the entrainment of SF-1-mediated
      transcriptional events. In addition, the current study demonstrates that specific
      enzymatic activities are capable of regulating distinct facets of a highly
      ordered transcriptional response.

PMID- 16109737
TI  - Serotonin (5-HT) receptor subtypes mediate specific modes of 5-HT-induced
      signaling and regulation of neurosecretion in gonadotropin-releasing hormone
      neurons.
AB  - Serotonin (5-HT), the endogenous nonselective 5-HT receptor agonist, activates
      the inositol 1,4,5-triphosphate/calcium (InsP3/Ca2+) signaling pathway and exerts
      both stimulatory and inhibitory actions on cAMP production and GnRH release in
      immortalized GnRH neurons. The high degree of similarity between the signaling
      and secretory responses elicited by GnRH and 5-HT prompted us to target specific
      5-HT receptor subtypes to deconvolute the complex actions of these agonists on
      signal transduction and GnRH release. Specific mRNA transcripts for 5-HT1A, 5
      HT2C, 5-HT4, and 5-HT7 were identified in immortalized GnRH neurons (GT1-7). The
      rate of firing of spontaneous action potentials (APs) by hypothalamic GnRH
      neurons and cAMP production and pulsatile GnRH release in GT17 cells were
      profoundly inhibited during activation of the Gi-coupled 5-HT1A receptor.
      Treatment with a selective agonist to activate the Gq-coupled 5-HT2C receptor
      increased the rate of firing of spontaneous APs, stimulated InsP3 production and
      caused a delayed increase in GnRH release. Selective activation of the Gs-coupled
      5-HT4 receptor also increased the rate of firing of APs, stimulated cAMP
      production, and caused a sustained and robust increase in GnRH release. The
      ability of 5-HT receptor subtypes expressed in GnRH neurons to activate single or
      multiple G proteins in a time- and dose-dependent manner differentially regulates
      the phospholipase C/InsP3/Ca2+, and adenylyl cyclase/cAMP signaling pathways, and
      thereby regulates the frequency and amplitude of pulsatile GnRH release. This
      process, in conjunction with the modulation of spontaneous electrical activity of
      the GnRH neuron, contributes to the control of the pulsatile mode of neuropeptide
      secretion that is characteristic of GnRH neuronal function in vivo and in vitro.

PMID- 16109738
TI  - Association of the mSin3A-histone deacetylase 1/2 corepressor complex with the
      mouse steroidogenic acute regulatory protein gene.
AB  - Several factors have been identified in the transcriptional repression of the
      steroidogenic acute regulatory protein (StAR) gene promoter; yet, no associating
      corepressor complexes have been characterized for the mouse promoter in MA-10
      mouse Leydig tumor cells. We now report that Sp3, CAGA element binding proteins,
      and a corepressor complex consisting of mSin3A, histone deacetylase (HDAC)1, and
      HDAC2 associates with a transcriptional repressor region within the mouse StAR
      promoter. 5'-Promoter deletion analysis localized the negative regulatory region
      between -180 and -150 bp upstream of the transcription start site, and mutations
      in both the CAGA and Sp binding elements were required to relieve the repression
      of basal StAR promoter activity. Protein-DNA binding analysis revealed Sp3 and
      specific CAGA element-binding protein(s) associated with the repressor region.
      Coimmunoprecipitation analysis identified the presence of the mSin3A, HDAC1, and
      HDAC2 corepressor complex in MA-10 cells. Furthermore, chromatin
      immunoprecipitation assays revealed Sp3, mSin3A, and HDAC1/2 association with the
      proximal region of the StAR promoter in situ. In addition, HDAC inhibition
      resulted in a dose-dependent activation of a mouse StAR reporter construct,
      whereas mutations within the repressor region diminished this effect by 44%. In
      sum, these data support a novel regulatory mechanism for transcriptional
      repression of the mouse StAR promoter by DNA binding of Sp3 and CAGA element
      binding proteins, and association of the Sin3 corepressor complex exhibiting HDAC
      activity.

PMID- 16109740
TI  - Shift from biliary to urinary elimination of acetaminophen-glucuronide in
      acetaminophen-pretreated rats.
AB  - Despite its toxicity, acetaminophen (APAP) is used increasingly as an analgesic,
      antipyretic, and anti-inflammatory agent. We examined the effect of prior
      exposure to APAP on its biliary and urinary elimination. The biliary and urinary
      elimination of a test dose of APAP (150 mg/kg i.v.) was determined in male Wistar
      rats 24 h after pretreatment with vehicle, a single dose (1.0 g/kg i.p.), or
      increasing daily doses (0.2, 0.3, 0.6, and 1.0 g/kg/day i.p.) of APAP. Although
      elimination of the parent APAP was minimally affected, biliary excretion of APAP
      glucuronide was significantly decreased 70 and 80%, whereas urinary excretion was
      significantly increased 90 and 100% in the groups pretreated with single and
      repeated doses of APAP, respectively, relative to vehicle controls. Western
      analysis and confocal immunofluorescent microscopy indicated a marked increase in
      hepatic expression of multidrug resistance-associated protein 3 (Mrp3) in both
      groups pretreated with APAP, relative to expression of Mrp2. ATP-dependent
      transport of [3H]taurocholate, an Mrp3 substrate, was significantly increased in
      basolateral liver plasma membrane vesicles from rats pretreated with repeated
      doses of APAP relative to controls. Enterohepatic recirculation of APAP
      glucuronide after administration of the same test dose of the drug was
      significantly decreased in rats pretreated with repeated doses of APAP. These
      data indicate that APAP pretreatment induced a shift from biliary to urinary
      elimination of APAP glucuronide, consistent with the increased expression of Mrp3
      in the basolateral domain of the hepatocyte. We postulate that decreased
      enterohepatic recirculation contributes to decreased APAP hepatotoxicity by
      reducing liver exposure.

PMID- 16109739
TI  - The breast cancer susceptibility gene BRCA1 regulates progesterone receptor
      signaling in mammary epithelial cells.
AB  - The progesterone receptor (PR) plays roles in normal mammary development and
      breast cancer formation, where it may exert both stimulatory and inhibitory
      actions. Previously, the breast cancer susceptibility gene product BRCA1 was
      found to interact with and inhibit the transcriptional activity of estrogen
      receptor-alpha. In this study, we found that exogenous wild-type BRCA1 inhibited
      the activity of the PR in transient transfection assays utilizing a mouse mammary
      tumor virus-Luc reporter. Wild-type BRCA1 inhibited the activity of endogenous PR
      in human breast cancer cells (T47D and MCF-7) and inhibited the activity of
      exogenous PR-A, PR-B, and [PR-A plus PR-B] isoforms. On the other hand, knockdown
      of endogenous BRCA1 using small interfering RNA enhanced the progesterone
      stimulated activity of the PR by about 4-fold. We documented an in vivo
      association of the endogenous BRCA1 with PR isoforms A and B and a direct in
      vitro interaction between BRCA1 and PR, which was partially mapped. Whereas down
      regulation of the coactivator p300 contributes to the BRCA1-mediated repression
      of estrogen receptor-alpha, this mechanism does not contribute to inhibition of
      PR activity, because exogenous p300 did not rescue the BRCA1 repression of PR
      activity. The BRCA1-PR interaction has functional consequences. Thus, we showed
      that BRCA1 inhibits the expression of various endogenous progesterone-responsive
      genes and inhibits progesterone-stimulated proliferation of T47D cells. Finally,
      exogenous progesterone caused an exaggerated proliferative response in the
      mammary glands of mice harboring a mammary-targeted conditional deletion of the
      full-length isoform of Brca1. These findings suggest that BRCA1 regulates the
      activity of progesterone, a major hormone of pregnancy that may also participate
      in mammary carcinogenesis.

PMID- 16109741
TI  - Glucocorticoid hormone regulates the circadian coordination of micro-opioid
      receptor expression in mouse brainstem.
AB  - The 24-h variation in glucocorticoid secretion from the adrenal cortex is
      observed not only in nocturnally active rodents but also in diurnally active
      humans. Although the cyclic change in circulating glucocorticoid levels is
      thought to influence the efficacy and/or toxicity of many drugs, the mechanism
      underlying the influence remains poorly understood. In this study, we demonstrate
      that the 24-h variation in circulating glucocorticoid levels modulates the
      analgesic effect of morphine by regulating the expression of the mu-opioid
      receptor. Significant time-dependent variations in the mRNA levels of the mu
      opioid receptor and its binding capacity were observed in mouse brainstem. The
      analgesic effect of morphine was enhanced by administering the drug when mu
      opioid receptor levels were increased. However, corticotrophin-releasing hormone
      (CRH)-deficient mice, disrupting the 24-h rhythm of glucocorticoid secretion,
      showed no significant time-dependent variation in the expression of the mu-opioid
      receptor. As a consequence, there was no significant dosing time-dependent
      difference in the analgesic effect of morphine in CRH-deficient mice. A single
      administration of corticosterone significantly induced the expression of the mu
      opioid receptor in the CRH-deficient mouse brainstem and also enhanced the
      analgesic effect of morphine. These findings suggest a mechanism underlying the
      time-dependent variation in mu-opioid receptor function and provide clues to
      select the most appropriate time of day for administration of morphine.

PMID- 16109742
TI  - A prostacyclin receptor antagonist inhibits the sensitized release of substance P
      from rat sensory neurons.
AB  - Prostacyclin, one of the cyclooxygenase metabolites, causes various biological
      effects, including vasodilation and antithrombogenicity, and is also involved in
      several pathophysiological effects, such as inflammatory pain and bladder
      disorders. The prostacyclin receptor (IP receptor) agonists iloprost, cicaprost,
      and carbacyclin have been useful for clarifying the role of the IP receptor
      signaling, since the endogenous ligand, prostacyclin, is very unstable. On the
      other hand, only a few IP receptor antagonists have been reported to date. Here,
      we characterized the biological activities of 2-[4-(1H-indol-4-yloxymethyl)
      benzyloxycarbonylamino]-3-phenyl-propionic acid (compound A) in various in vitro
      systems. Compound A inhibited the accumulation of the second messenger cyclic AMP
      in the UMR-108 rat osteosarcoma cell line and primary cultured rat dorsal root
      ganglion (DRG) neurons in a concentration-dependent manner up to 10 microM,
      without affecting other eicosanoid receptors. Functionally, the IP receptor plays
      an important role in DRG neuron sensitization, which is measured by release of
      the neurotransmitter substance P. Although the effects of iloprost or Lys
      bradykinin, an inflammatory peptide, alone on substance P release were limited,
      stimulation of the neurons with both these ligands induced substantial amounts of
      substance P release. This synergistic effect was suppressed by compound A.
      Collectively, these results suggest that compound A is a highly selective IP
      receptor antagonist that inhibits iloprost-induced sensitization of sensory
      neurons. Furthermore, these findings suggest that IP receptor antagonist
      administration may be effective for abnormal neural activities of unmyelinated
      sensory afferents. Compound A should prove useful for further investigations of
      the IP receptor in various biological processes.

PMID- 16109743
TI  - BP-1107 [{2-[4-(2,4-dioxo-thiazolidin-5-ylmethyl)-phenoxy]-ethyl}-methyl-amide]:
      a novel synthetic thiazolidinedione that inhibits epidermal hyperplasia in
      psoriatic skin-severe-combined immunodeficient mouse transplants after topical
      application.
AB  - Recent studies have demonstrated that orally administered thiazolidinedione
      ligands of the peroxisome proliferator-activated receptor-gamma can ameliorate
      clinical features of psoriasis in humans. Thiazolidinediones also inhibit the
      proliferation of psoriatic keratinocytes in monolayer and organ culture, and at
      least one of these agents (troglitazone) inhibits epidermal hyperplasia of human
      psoriatic skin transplanted to severe-combined immunodeficient (SCID) mice. In
      the present study, we show that a novel, synthetic, thiazoladinedione derivative,
      BP-1107 ({2-[4-(2,4-dioxo-thiazolidin-5-ylmethyl)-phenoxy]-ethyl}-methyl-amide),
      is capable of inhibiting psoriatic hyperplasia in the SCID mouse transplant model
      after topical application. Like other thiazolidinediones, BP-1107 inhibits
      proliferation of rapidly growing keratinocytes in monolayer culture, but compared
      with these agents, the effective dose of BP-1107 needed to suppress keratinocyte
      proliferation is much lower. Concentrations of BP-1107 that effectively inhibit
      keratinocyte function have no detrimental effect on dermal fibroblasts. These
      data suggest that effective topical antipsoriatic therapy may be provided with
      this agent.

PMID- 16109744
TI  - Perturbation of voltage-sensitive Ca2+ channel function by volatile organic
      solvents.
AB  - The mechanisms underlying the acute neurophysiological and behavioral effects of
      volatile organic compounds (VOCs) remain to be elucidated. However, the function
      of neuronal ion channels is perturbed by VOCs. The present study examined effects
      of toluene (TOL), trichloroethylene (TCE), and perchloroethylene (PERC) on whole
      cell calcium current (ICa) in nerve growth factor-differentiated pheochromocytoma
      (PC12) cells. All three VOCs affected ICa in a reversible, concentration
      dependent manner. At +10-mV test potentials, VOCs inhibited ICa, whereas at test
      potentials of -20 and -10 mV, they potentiated it. The order of potency for
      inhibition (IC50) was PERC (270 microM) > TOL (720 microM) > TCE (1525 microM).
      VOCs also changed ICa inactivation kinetics from a single- to double-exponential
      function. Voltage-ramp experiments suggested that VOCs shifted ICa activation in
      a hyperpolarizing direction; this was confirmed by calculating the half-maximal
      voltage of activation (V1/2, act) in the absence and presence of VOCs using the
      Boltzman equation. V(1/2, act) was shifted from approximately -2 mV in control to
      -11, -12, and -16 mV by TOL, TCE, and PERC, respectively. Similarly, VOCs shifted
      the half-maximal voltage of steady-state inactivation (V1/2, inact) from
      approximately -16 mV in control to -32, -35, and -20 mV in the presence of TOL,
      TCE, and PERC, respectively. Inhibition of ICa by TOL was confirmed in primary
      cultures of cortical neurons, where 827 microM TOL inhibited current by 61%.
      These data demonstrate that VOCs perturb voltage-sensitive Ca2+ channel function
      in neurons, an effect that could contribute to the acute neurotoxicity of these
      compounds.

PMID- 16109745
TI  - ORIOGEN: order restricted inference for ordered gene expression data.
AB  - ORIOGEN is a user-friendly Java-based software package for selecting and
      clustering genes according to their profiles across various treatment groups. In
      particular, ORIOGEN is useful for analyzing data obtained from time-course or
      dose-response type experiments. AVAILABILITY: The ORIOGEN software can be
      downloaded freely from http://dir.niehs.nih.gov/dirbb/oriogen/index.cfm CONTACT:
      peddada@niehs.nih.gov (for statistical questions) and oriogen@constellagroup.com
      (for software support) SUPPLEMENTARY INFORMATION: ORIOGEN has a full set of help
      files. Also, an example input file is provided with the download.

PMID- 16109746
TI  - A statistical model providing comprehensive predictions for the mRNA differential
      display.
AB  - MOTIVATION: Differential display (DD) or arbitrarily primed fingerprinting serves
      to identify differentially expressed genes, but these techniques cannot determine
      how many of the theoretically available genes have been uncovered. Previous
      mathematical models are unsatisfying as they are not suitable to analyze
      experimental data. RESULTS: In the present study, we provide a statistical model
      based on the redundancy of cDNA fragments amplified during DD experiments. This
      model is applicable to any DD and predicts (1) the total number of genes
      expressed in a sample cell type or tissue, (2) the number of differentially
      expressed genes, (3) the coverage obtained with any given number of primer
      combinations. In a DD experiment comparing two developmental stages of the post
      natal rat inner ear, we estimated the total number of differentially expressed
      genes accessible by DD to be 445, and the number of primer combinations required
      to uncover 90% of these to be 127. AVAILABILITY: The algorithms were implemented
      in Matlab (The Mathworks, Inc., Natick, MA) environment and are available at
      www.physiologie.uni-freiburg.de/download.html CONTACT:
      ellen.reisinger@physiologie.uni-freiburg.de.

PMID- 16109747
TI  - Virtual Footprint and PRODORIC: an integrative framework for regulon prediction
      in prokaryotes.
AB  - SUMMARY: A new online framework for the accurate and integrative prediction of
      transcription factor binding sites (TFBSs) in prokaryotes was developed. The
      system consists of three interconnected modules: (1) The PRODORIC database as a
      comprehensive data source and extensive collection of TFBSs with corresponding
      position weight matrices. (2) The pattern matching tool Virtual Footprint for the
      prediction of genome based regulons and for the analysis of individual promoter
      regions. (3) The interactive genome browser GBPro for the visualization of TFBS
      search results in their genomic context and links to gene and regulator-specific
      information in PRODORIC. The aim of this service is to provide researchers a free
      and easy to use collection of interconnected tools in the field of molecular
      microbiology, infection and systems biology. AVAILABILITY:
      http://www.prodoric.de/vfp.

PMID- 16109748
TI  - Non-linear PCA: a missing data approach.
AB  - MOTIVATION: Visualizing and analysing the potential non-linear structure of a
      dataset is becoming an important task in molecular biology. This is even more
      challenging when the data have missing values. RESULTS: Here, we propose an
      inverse model that performs non-linear principal component analysis (NLPCA) from
      incomplete datasets. Missing values are ignored while optimizing the model, but
      can be estimated afterwards. Results are shown for both artificial and
      experimental datasets. In contrast to linear methods, non-linear methods were
      able to give better missing value estimations for non-linear structured data.
      APPLICATION: We applied this technique to a time course of metabolite data from a
      cold stress experiment on the model plant Arabidopsis thaliana, and could
      approximate the mapping function from any time point to the metabolite responses.
      Thus, the inverse NLPCA provides greatly improved information for better
      understanding the complex response to cold stress. CONTACT: scholz@mpimp
      golm.mpg.de.

PMID- 16109749
TI  - Structure clustering features on the Sfold Web server.
AB  - The energy landscape of RNA secondary structures is often complex, and the
      Boltzmann-weighted ensemble usually contains distinct clusters. Furthermore, the
      minimum free energy structure often lies outside of the cluster containing the
      structure determined by comparative sequence analysis. We have developed
      procedures to characterize and visualize the Boltzmann-weighted ensemble, and
      have made them available on the Sfold Web server. The new features on the Web
      server include clustering statistics, ensemble and cluster centroids, multi
      dimensional scaling display and energy landscape representation of the Boltzmann
      weighted ensemble. AVAILABILITY: http://sfold.wadsworth.org;
      http://www.bioinfo.rpi.edu/applications/sfold CONTACT: chanc@wadsworth.org.

PMID- 16109751
TI  - Brain stimulation reveals critical auditory naming cortex.
AB  - One challenge in dominant temporal lobe epilepsy surgery is to remove sufficient
      epileptogenic tissue without compromising post-operative language functioning.
      Pre-resection electrical stimulation mapping enables identification of language
      areas that can be spared from resection, and also provides a unique opportunity
      to investigate brain-language relationships. Visual object naming is the gold
      standard for identifying 'essential' language cortex; however, sparing visual
      naming (VN) sites has not reliably prevented post-operative language decline. In
      addition to visual object naming, we included a more 'ecologically valid'
      auditory description naming task in our pre-resection cortical mapping protocol.
      Of the seven patients who had auditory naming (AN) sites removed, six declined
      post-operatively, whereas of the 12 patients who did not have AN sites removed,
      only 3 declined post-operatively (P = 0.02), suggesting an association between AN
      site removal and post-operative naming decline. Interestingly, although VN sites
      were preserved in all patients, AN site removal resulted in decline in both
      auditory and VN tasks. These findings not only have potentially critical clinical
      significance, but also argue for modality specificity, with considerable
      integration within the semantic system.

PMID- 16109750
TI  - Changes in electrophysiological properties and sodium channel Nav1.3 expression
      in thalamic neurons after spinal cord injury.
AB  - Spinal cord contusion injury (SCI) is known to induce pain-related behaviour, as
      well as hyperresponsiveness in lumbar dorsal horn nociceptive neurons associated
      with the aberrant expression of Na(v)1.3, a rapidly repriming voltage-gated
      sodium channel. Many of these second-order dorsal horn neurons project to third
      order neurons in the ventrobasal complex of the thalamus. In this study we
      hypothesized that, following SCI, neurons in the thalamus undergo
      electrophysiological changes linked to aberrant expression of Na(v)1.3. Adult
      male Sprague-Dawley rats underwent contusion SCI at the T9 thoracic level. Four
      weeks post-SCI, Na(v)1.3 protein was upregulated within thalamic neurons in
      ventroposterior lateral (VPL) and ventroposterior medial nuclei, where
      extracellular unit recordings revealed increased spontaneous discharge,
      afterdischarge, hyperresponsiveness to innocuous and noxious peripheral stimuli,
      and expansion of peripheral receptive fields. Altered electrophysiological
      properties of VPL neurons persisted after interruption of ascending spinal
      barrage by spinal cord transection above the level of the injury. Lumbar
      intrathecal administration of specific antisense oligodeoxynucleotides generated
      against Na(v)1.3 caused a significant reduction in Na(v)1.3 expression in
      thalamic neurons and reversed electrophysiological alterations. These results
      show, for the first time, a change in sodium channel expression within neurons in
      the thalamus after injury to the spinal cord, and suggest that these changes
      contribute to altered processing of somatosensory information after SCI.

PMID- 16109752
TI  - CMA okays private health care for waiting patients.

PMID- 16109753
TI  - Isolation and characterization of bipotent liver progenitor cells from adult
      mouse.
AB  - Liver progenitor cells have drawn a great deal of attention both for their
      therapeutic potential and for their usefulness in exploring the molecular events
      surrounding liver development and regeneration. Despite the intensive studies on
      liver progenitors from rats, equivalent progenitor cells derived from mice are
      relatively rare. We used retrosine treatment followed by partial hepatectomy to
      elicit liver progenitors in mice. From these animals showing prominent ductular
      reactions, mouse-derived liver progenitor cell lines (LEPCs) were isolated by
      single-cell cloning. Phenotypic and lineage profiling of the LEPC clones were
      performed using immunochemistry, reverse transcription-polymerase chain reaction,
      and a dual-color system comprising the reporter EGFP under the control of the
      cytokeratin 19 promoter and the DsRed reporter under the control of the albumin
      promoter. LEPCs expressed liver progenitor cell markers. LEPCs also expressed
      some markers shared by bone marrow-derived hematopoietic stem cells c-Kit and Thy
      1 but not CD34 and CD45. When cultured as aggregates in Matrigel, LEPCs
      differentiated into hepatocyte upon treatment with 50 ng/ml epithelial growth
      factor or differentiated into biliary lineage cells upon treatment with 20 ng/ml
      hepatocyte growth factor. In the presence of 2% dimethyl sulfoxide and 2%
      Matrigel, LEPCs acquired predominantly bile lineage phenotypes, with occasional
      patches of cells exhibiting hepatocyte phenotypes. Upon transplantation into CCl4
      injured-liver, LEPCs engrafted into liver parenchyma and differentiated into
      hepatocytes. Considering the amenability of the mouse to genetic manipulation,
      these mouse-derived LEPCs may be useful tools as in vitro models to study
      molecular events in liver development and regeneration and can shed light in
      studying the therapy potential of liver stem cells.

PMID- 16109754
TI  - Treatment of senile osteoporosis in SAMP6 mice by intra-bone marrow injection of
      allogeneic bone marrow cells.
AB  - A substrain of the senescence-accelerated mouse, SAMP6 (senescence-accelerated
      mouse prone 6), spontaneously develops osteoporosis early in life. Therefore,
      this strain is a useful animal model for developing new strategies for the
      treatment of osteoporosis in humans. We succeeded in treating osteoporosis in
      SAMP6 mice after the onset of this disease, using a newly developed method of
      bone marrow transplantation (BMT): Allogeneic bone marrow cells obtained from
      normal mouse strains were directly injected into the bone marrow cavity of
      irradiated SAMP6 mice (intra-bone marrow BMT [IBM-BMT]). After the treatment with
      IBM-BMT, hematolymphoid cells were completely reconstituted by donor-derived
      cells, and bone marrow stromal cells were also found to be of donor origin. The
      treated SAMP6 mice showed histologically-normal trabecular bone. In addition,
      bone mineral density and urinary deoxypiridinoline, a hallmark of bone
      destruction, were normalized. When the message levels of cytokines (tumor
      necrosis factor alpha, interleukin-6 [IL-6], IL-11, and receptor activator of
      nuclear factor-kappa B ligand [RANKL]) were examined, IL-11, RANKL (from bone
      marrow stromal cells), and IL-6 (from osteoclasts), which regulate bone
      remodeling, were restored to levels similar to those in normal B6 mice. These
      findings indicate that not only the hemopoietic system but also the bone marrow
      microenvironment were normalized after IBM-BMT, resulting in an amelioration of
      the imbalance between bone absorption and formation.

PMID- 16109755
TI  - Induction of differentiation of embryonic stem cells into insulin-secreting cells
      by fetal soluble factors.
AB  - Cell signals produced during pancreas embryogenesis regulate pancreatic
      differentiation. We show that the developing pancreas releases soluble factors
      responsible for in vitro endocrine pancreatic differentiation from embryonic stem
      cells (ESCs). A mouse D3 ESC line was transfected with a human insulin
      promoter/betageo/phosphoglycerate kinase-hygromycin-resistant construct. To
      direct differentiation, cells were cultured for 7 days to form embryoid bodies
      and then plated for an additional 7 days. During this 14-day period, besides
      eliminating leukemia inhibitory factor, cells were cultured in low serum
      concentration with the addition of conditioned media from embryonic day-16.5
      pancreatic buds. Islet cell differentiation was studied by the following: (a) X
      gal staining after neomycin selection, (b) BrdU (bro-modeoxyuridine) studies, (c)
      simple and double immunohistochemistry for insulin, C-peptide, and glucose
      transporter 2 (Glut-2), (d) reverse transcription-polymerase chain reaction for
      insulin and pancreas duodenum homeobox 1 (PDX-1), (e) insulin and C-peptide
      content and secretion assays, (f) intraperitoneal glucose tolerance test, (g)
      electrophysiology (patch-clamp studies in inside-out configuration), and (h)
      transplantation of differentiated cells under the kidney capsule of
      streptozotocin-diabetic mice. The differentiated ESCs showed the following:
      changes in the mRNA levels of insulin and PDX-1; coexpression of insulin, C
      peptide, and Glut-2; glucose and tolbutamide-dependent insulin and C-peptide
      release; K-channel activity regulated by ATP; and normalization of blood glucose
      levels after transplantation into diabetic mice and hyperglycemia after graft
      removal. In this study, we establish a battery of techniques that could be used
      together to properly characterize islet cell differentiation. Moreover,
      identification of factors released by the developing pancreas may be instrumental
      in engineering beta cells from stem cells.

PMID- 16109756
TI  - Hepatocyte growth factor delivered by ultrasound-mediated destruction of
      microbubbles induces proliferation of cardiomyocytes and amelioration of left
      ventricular contractile function in Doxorubicin-induced cardiomyopathy.
AB  - At present, there is no curative strategy for advanced cardiomyopathy except for
      cardiac transplantation, which is not easily performed, mainly due to a shortage
      of donors. It has been reported that myocardial progenitor cells exist even in
      the postnatal heart, suggesting that myocardial progenitor cells could
      proliferate under some situations and might improve cardiac function in
      cardiomyopathy-induced hearts. In this study, recombinant human hepatocyte growth
      factor (rhHGF) was delivered using ultrasound-mediated destruction of
      microbubbles (UMDM) into the cardiomyopathy-induced heart by doxorubicin (20
      mg/kg). Intravenous injection of rhHGF (IV-rhHGF) alone or UMDM alone failed to
      improve the morphology or the function of the cardiomyopathy-induced heart, but
      (IV-rhHGF + UMDM) treatment significantly improved the heart morphologically and
      functionally, and repetitive treatments of (IV-rhHGF + UMDM) enhanced the
      effects. The number of bromodeoxy-uridine-positive cardiomyocytes significantly
      increased in the (IV-rhHGF + UMDM)-treated hearts compared with the untreated
      hearts. Moreover, Sca-1+ myocardial progenitor cells express c-Met, a receptor
      for HGF. These results suggest that (IV-rhHGF + UMDM) treatment could
      morphologically and functionally improve the heart in the case of doxorubicin
      induced cardiomyopathy through the proliferation of the myocardial progenitor
      cells.

PMID- 16109757
TI  - Reconstruction of chemically burned rat corneal surface by bone marrow-derived
      human mesenchymal stem cells.
AB  - To examine whether transplantation of human mesenchymal stem cells (MSCs) could
      reconstruct the corneal damage and also whether grafted MSCs could differentiate
      into corneal epithelial cells, we isolated MSCs from healthy donors. After growth
      and expansion on amniotic membrane, cells were transplanted into rat corneas 7
      days after chemical burns. Reconstruction of the damaged cornea and the rat
      vision were measured once a week by slit lamp and by an optokinetic head-tracking
      instrument, respectively. Corneas were then cut out, fixed, and imbedded for
      immunofluorescent study of the expression of keratin 3 and keratin-pan as
      epithelial cell markers. Expression of CD45, interleukin 2, and metalloproteinase
      2 was also investigated for inflammation and inflammation-related angiogenesis.
      The data showed that transplantation of MSCs, like limbal epithelial stem cells,
      successfully reconstructed damaged rat corneal surface. Interestingly, the
      therapeutic effect of the transplantation may be associated with the inhibition
      of inflammation and angiogenesis after transplantation of MSCs rather than the
      epithelial differentiation from MSCs. This study provides the first line of
      evidence that MSCs can be used for reconstruction of damaged corneas, presenting
      a new source for autotransplantation in the treatment of corneal disorders.

PMID- 16109758
TI  - Establishment of novel embryonic stem cell lines derived from the common marmoset
      (Callithrix jacchus).
AB  - The successful establishment of human embryonic stem cell (hESC) lines has
      inaugurated a new era in regenerative medicine by facilitating the
      transplantation of differentiated ESCs to specific organs. However, problems with
      the safety and efficacy of hESC therapy in vivo remain to be resolved.
      Preclinical studies using animal model systems, including nonhuman primates, are
      essential to evaluate the safety and efficacy of hESC therapies. Previously, we
      demonstrated that common marmosets are suitable laboratory animal models for
      preclinical studies of hematopoietic stem cell therapies. As this animal model is
      also applicable to preclinical trials of ESC therapies, we have established novel
      common marmoset ESC (CMESC) lines. To obtain marmoset embryos, we developed a new
      embryo collection system, in which blastocysts can be obtained every 3 weeks from
      each marmoset pair. The inner cell mass was isolated by immunosurgery and plated
      on a mouse embryonic feeder layer. Some of the CMESC lines were cultured
      continuously for more than 1 year. These CMESC lines showed alkaline phosphatase
      activity and expressed stage-specific embryonic antigen (SSEA)-3, SSEA-4, TRA-1
      60, and TRA-1-81. On the other hand, SSEA-1 was not detected. Furthermore, our
      novel CMESCs are pluripotent, as evidenced by in vivo teratoma formation in
      immunodeficient mice and in vitro differentiation experiments. Our established
      CMESC lines and the common marmoset provide an excellent experimental model
      system for understanding differentiation mechanisms, as well as the development
      of regenerative therapies using hESCs.

PMID- 16109759
TI  - Characterization of the optimal culture conditions for clinical scale production
      of human mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells defined by multilineage
      potential, ease to gene modification, and immunosuppressive ability, thus holding
      promise for tissue engineering, gene therapy, and immunotherapy. They exhibit a
      unique in vitro expansion capacity, which, however, does not compensate for the
      very low percentage in their niches given the vast numbers of cells required for
      the relative studies. Taking into consideration the lack of a uniform approach
      for MSC isolation and expansion, we attempted in this study, by comparing various
      culture conditions, to identify the optimal protocol for the large-scale
      production of MSCs while maintaining their multilineage and immunosuppressive
      capacities. Our data indicate that, apart from the quality of fetal calf serum,
      other culture parameters, including basal medium, glucose concentration, stable
      glutamine, bone marrow mononuclear cell plating density, MSC passaging density,
      and plastic surface quality, affect the final outcome. Furthermore, the use of
      basic fibroblast growth factor (bFGF), the most common growth supplement in MSC
      culture media, greatly increases the proliferation rate but also upregulates HLA
      class I and induces low HLA-DR expression. However, not only does this
      upregulation not elicit significant in vitro allogeneic T cell responses, but
      also bFGF-cultured MSCs exhibit enhanced in vivo immunosuppressive potential.
      Besides, addition of bFGF affects MSC multilineage differentiation capacity,
      favoring differentiation toward the osteogenic lineage and limiting neurogenic
      potential. In conclusion, in this report we define the optimal culture conditions
      for the successful isolation and expansion of human MSCs in high numbers for
      subsequent cellular therapeutic approaches.

PMID- 16109760
TI  - Effects of three-dimensional culture and growth factors on the chondrogenic
      differentiation of murine embryonic stem cells.
AB  - Embryonic stem (ES) cells have the ability to self-replicate and differentiate
      into cells from all three germ layers, holding great promise for tissue
      regeneration applications. However, controlling the differentiation of ES cells
      and obtaining homogenous cell populations still remains a challenge. We
      hypothesize that a supportive three-dimensional (3D) environment provides ES cell
      derived cells an environment that more closely mimics chondrogenesis in vivo. In
      the present study, the chondrogenic differentiation capability of ES cell-derived
      embryoid bodies (EBs) encapsulated in poly(ethylene glycol)-based (PEG) hydrogels
      was examined and compared with the chondrogenic potential of EBs in conventional
      monolayer culture. PEG hydrogel-encapsulated EBs and EBs in monolayer were
      cultured in vitro for up to 17 days in chondrogenic differentiation medium in the
      presence of transforming growth factor (TGF)-beta1 or bone morphogenic protein-2.
      Gene expression and protein analyses indicated that EB-PEG hydrogel culture
      upregulated cartilage-relevant markers compared with a monolayer environment and
      induction of chondrocytic phenotype was stimulated with TGF-beta1. Histology of
      EBs in PEG hydrogel culture with TGF-beta1 demonstrated basophilic extracellular
      matrix deposition characteristic of neocartilage. These findings suggest that EB
      PEG hydrogel culture, with an appropriate growth factor, may provide a suitable
      environment for chondrogenic differentiation of intact ES cell-derived EBs.

PMID- 16109761
TI  - Testicular cell conditioned medium supports differentiation of embryonic stem
      cells into ovarian structures containing oocytes.
AB  - Previous reports and the current study have found that germ cell precursor cells
      appear in embryoid bodies (EBs) formed from mouse embryonic stem cells as
      identified by positive expression of specific germ cell markers such as Oct-3/4,
      Mvh, c-kit, Stella, and DAZL. We hypothesized that if exposed to appropriate
      growth factors, the germ cell precursor cells within the EBs would differentiate
      into gametes. The source for growth factors used in the present study is
      conditioned medium collected from testicular cell cultures prepared from the
      testes of newborn males. Testes at this stage of development contain most growth
      factors required for the transformation of germ stem cells into differentiated
      gametes. When EBs were cultured in the conditioned medium, they developed into
      ovarian structures, which contained putative oocytes. The oocytes were surrounded
      by one to two layers of flattened cells and did not have a visible zona
      pellucida. However, oocyte-specific markers such as Fig-alpha and ZP3 were found
      expressed by the ovarian structures. The production of oocytes using this method
      is repeatable and reliable and may be applicable to other mammalian species,
      including the human.

PMID- 16109762
TI  - Human embryonic stem cells and their differentiated derivatives are less
      susceptible to immune rejection than adult cells.
AB  - Differentiated cell types derived from human embryonic stem cells (hESCs) may
      serve in the future to treat various human diseases. A crucial step toward their
      successful clinical application is to examine the immune response that might be
      launched against them after transplantation. We used two experimental platforms
      to examine the in vivo leukocyte response toward hESCs. First, immunocompetent
      and immunodeficient mouse strains were used to identify T cells as the major
      component that causes xenorejection of hESCs. Second, mice that were conditioned
      to carry peripheral blood leukocytes from human origin were used to test the
      human leukocyte alloresponse toward undifferentiated and differentiated hESCs.
      Using this model, we have detected only a minute immune response toward
      undifferentiated as well as differentiated hESCs over the course of 1 month,
      although control adult grafts were repeatedly infiltrated with lymphocytes and
      destroyed. Our data show that the cells evade immune destruction due to a low
      immunostimulatory potential. Nevertheless, a human cytotoxic T lymphocyte clone
      that was specifically prepared to recognize two hESC lines could lyse the cells
      after major histocompatibility complex class I (MHC-I) induction. Although MHC-I
      levels in hESCs are sufficient for rejection by cytotoxic T cells, our data
      suggest that the immunostimulatory capacity of the cells is very low. Thus,
      immunosuppressive regimens for hESC-based therapeutics could be highly reduced
      compared with conventional organ transplantation because direct allorejection
      processes of hESCs and their derivatives are considerably weaker.

PMID- 16109763
TI  - Cytokine-dependent proliferation of human CD34+ progenitor cells in the absence
      of serum is suppressed by their progeny's production of serine proteinases.
AB  - In this study, we demonstrate that the synthesis and release of serine
      proteinases by hematopoietic cells affects the in vitro proliferation of
      hematopoietic progenitor cells (HPCs) in response to proteins, including
      hematopoietic growth factors (HGFs), transferrin, insulin, and albumin in serum
      free cultures. In serum-free cultures, bone marrow mononuclear cells or the CD34-
      progeny of the CD34+ cells were shown to release the serine proteinases human
      neutrophil elastase (HNE), cathepsin G (Cath G), and proteinase 3 (Pr3). In the
      absence of serum, we showed that HNE, Cath G, and Pr3 rapidly and dose
      dependently degraded HGF and other proteins present in the medium, resulting in
      decreased proliferation of HPCs. Addition of the serine proteinase inhibitors
      alpha1-proteinase inhibitor (alpha1-PI) or the secretory leukocyte proteinase
      inhibitor (SLPI), but not leupeptin, aprotinin, or AEBSF (4-[2-aminoethyl]
      benzenesulfonylfluoride hydrochloride), could completely prevent the degradation
      of proteins relevant to the growth of hematopoietic cells. Thus, the addition of
      serine proteinase inhibitors like alpha1-PI or SLPI may be critical for the
      expansion of CD34+ cells or gene transfer into CD34+ cells or other hematopoietic
      cells in vitro using serum-free media under good manufacturing practice
      conditions.

PMID- 16109764
TI  - Optimizing techniques for tracking transplanted stem cells in vivo.
AB  - The potential for bone marrow-derived cells (BMDCs) to contribute to
      nonhematopoietic tissues has generated considerable debate in recent years.
      Causes for the controversies include disparities in the techniques used to track
      engraftment of BMDCs, inappropriate tissue preparation, a lack of appropriate
      positive and negative controls, and basic misunderstandings about how to properly
      collect and interpret images from epifluorescent and confocal microscopes. Our
      laboratory was among the first to use bone marrow transplants from transgenic
      mice constitutively expressing enhanced green fluorescent protein (GFP) to study
      the ability of BMDCs to give rise to nonhematopoietic tissue types, a system that
      is now in widespread use. During our 6 years of experience using GFP, as well as
      beta-galactosidase and the Y chromosome, to track BMDCs in vivo, we have
      identified many difficulties and have developed techniques to resolve them. We
      discuss several of these methods, and, in particular, we describe ratiometric
      analysis techniques for improving detection of transplanted cells derived from
      genetically modified bone marrow. Finally, to help resolve reported discrepancies
      regarding the frequency with which BMDCs contribute to skeletal myofibers, we
      demonstrate that the pattern of highly autofluorescent myofibers in skeletal
      muscle is clearly distinct from that of GFP-expressing myofibers and describe how
      unambiguous conclusions can be drawn from such data.

PMID- 16109765
TI  - Quality of research on community partnerships: developing the evidence base.
AB  - Recent years have witnessed broad public health transformations. Central to these
      changes is that partnership work is increasingly mandated and employed as a
      vehicle for health education and promotion and disease prevention. Such efforts
      involve partnerships that span National Health Service bodies, local authorities
      and health and social care organizations, with stakeholders from the public,
      private, voluntary and community sectors. However, a more adequate evidence base
      is required to guide policy and action. The aims of this paper are to draw
      attention to some of the issues that have hampered the quality of partnership
      research and to discuss ways in which this research can be improved, in an effort
      to encourage the development of a more valuable evidence base for researchers,
      practitioners and policy makers. Multimethod approaches to research on
      partnership context, functioning and outcomes are advocated, and policy
      recommendations are made.

PMID- 16109766
TI  - Transcription coactivator peroxisome proliferator-activated receptor-binding
      protein/mediator 1 deficiency abrogates acetaminophen hepatotoxicity.
AB  - Peroxisome proliferator-activated receptor-binding protein (PBP), also known as
      thyroid hormone receptor-associated protein 220/vitamin D receptor-interacting
      protein 205/mediator 1, an anchor for multisubunit mediator transcription
      complex, functions as a transcription coactivator for nuclear receptors.
      Disruption of the PBP gene results in embryonic lethality around embryonic day
      11.5 by affecting placental and multiorgan development. Here, we report that
      targeted deletion of PBP in liver parenchymal cells (PBP(Liv-/-)) results in the
      abrogation of hypertrophic and hyperplastic influences in liver mediated by
      constitutive androstane receptor (CAR) ligands phenobarbital (PB) and 1,4-bis-[2
      (3,5-dichloropyridyloxy)]benzene, and of acetaminophen-induced hepatotoxicity.
      CAR interacts with the two nuclear receptor-interacting LXXLL (L, leucine; X, any
      amino acid) motifs in PBP in a ligand-dependent manner. We also show that PBP
      interacts with the C-terminal portion of CAR, suggesting that PBP is involved in
      the regulation of CAR function. Although the full-length PBP only minimally
      increased CAR transcriptional activity, a truncated form of PBP (amino acids 487
      735) functioned as a dominant negative repressor, establishing that PBP functions
      as a coactivator for CAR. A reduction in CAR mRNA and protein level observed in
      PBP(Liv-/-) mouse liver suggests that PBP may regulate hepatic CAR expression.
      PBP-deficient hepatocytes in liver failed to reveal PB-dependent translocation of
      CAR to the nucleus. Adenoviral reconstitution of PBP in PBP(Liv-/-) mouse livers
      restored PB-mediated nuclear translocation of CAR as well as inducibility of
      CYP1A2, CYP2B10, CYP3A11, and CYP7A1 expression. We conclude that transcription
      coactivator PBP/TRAP220/MED1 is involved in the regulation of hepatic CAR
      function and that PBP deficiency in liver abrogates acetaminophen hepatotoxicity.

PMID- 16109767
TI  - Framework for kernel regularization with application to protein clustering.
AB  - We develop and apply a previously undescribed framework that is designed to
      extract information in the form of a positive definite kernel matrix from
      possibly crude, noisy, incomplete, inconsistent dissimilarity information between
      pairs of objects, obtainable in a variety of contexts. Any positive definite
      kernel defines a consistent set of distances, and the fitted kernel provides a
      set of coordinates in Euclidean space that attempts to respect the information
      available while controlling for complexity of the kernel. The resulting set of
      coordinates is highly appropriate for visualization and as input to
      classification and clustering algorithms. The framework is formulated in terms of
      a class of optimization problems that can be solved efficiently by using modern
      convex cone programming software. The power of the method is illustrated in the
      context of protein clustering based on primary sequence data. An application to
      the globin family of proteins resulted in a readily visualizable 3D sequence
      space of globins, where several subfamilies and subgroupings consistent with the
      literature were easily identifiable.

PMID- 16109769
TI  - Molecular path control in zeolite membranes.
AB  - We report molecular simulations of diffusion in confinement showing a phenomenon
      that we denote as molecular path control (MPC); depending on loading, molecules
      follow a preferred pathway. MPC raises the important question to which extent the
      loading may affect the molecular trajectories in nanoporous materials. Through
      MPC one is able to manually adjust the ratio of the diffusivities through
      different types of pores, and as an application one can direct the flow of
      diffusing particles in membranes forward or sideward by simply adjusting the
      pressure, without the need for mechanical parts like valves. We show that the key
      ingredient of MPC is the anisotropic nature of the nanoporous material that
      results in a complex interplay between different diffusion paths as a function of
      loading. These paths may be controlled by changing the loading, either through a
      change in pressure or temperature.

PMID- 16109768
TI  - Cytoplasmic SnoN in normal tissues and nonmalignant cells antagonizes TGF-beta
      signaling by sequestration of the Smad proteins.
AB  - TGF-beta is a ubiquitously expressed cytokine that signals through the Smad
      proteins to regulate many diverse cellular processes. SnoN is an important
      negative regulator of Smad signaling. It has been described as a nuclear protein,
      based on studies of ectopically expressed SnoN and endogenous SnoN in cancer cell
      lines. In the nucleus, SnoN binds to Smad2, Smad3, and Smad4 and represses their
      ability to activate transcription of TGF-beta target genes through multiple
      mechanisms. Here, we show that, whereas SnoN is localized exclusively in the
      nucleus in cancer tissues or cells, in normal tissues and nontumorigenic or
      primary epithelial cells, SnoN is predominantly cytoplasmic. Upon morphological
      differentiation or cell-cycle arrest, SnoN translocates into the nucleus. In
      contrast to nuclear SnoN that represses the transcriptional activity of the Smad
      complexes, cytoplasmic SnoN antagonizes TGF-beta signaling by sequestering the
      Smad proteins in the cytoplasm. Interestingly, cytoplasmic SnoN is resistant to
      TGF-beta-induced degradation and therefore is more potent than nuclear SnoN in
      repressing TGF-beta signaling. Thus, we have identified a mechanism of regulation
      of TGF-beta signaling via differential subcellular localization of SnoN that is
      likely to produce different patterns of downstream TGF-beta responses and may
      influence the proliferation or differentiation states of epithelial cells.

PMID- 16109770
TI  - Cell-specific deletion of glucosylceramide synthase in brain leads to severe
      neural defects after birth.
AB  - Sialic acid-containing glycosphingolipids, i.e., gangliosides, constitute a major
      component of neuronal cells and are thought to be essential for brain function.
      UDP-glucose:ceramide glucosyltransferase (Ugcg) catalyzes the initial step of
      glycosphingolipid (GSL) biosynthesis. To gain insight into the role of GSLs in
      brain development and function, a cell-specific disruption of Ugcg was performed
      as indicated by the absence of virtually all glucosylceramide-based GSLs. Shortly
      after birth, mice showed dysfunction of cerebellum and peripheral nerves,
      associated with structural defects. Axon branching of Purkinje cells was
      significantly reduced. In primary cultures of neurons, dendritic complexity was
      clearly diminished, and pruning occurred early. Myelin sheaths of peripheral
      nerves were broadened and focally severely disorganized. GSL deficiency also led
      to a down-regulation of gene expression sets involved in brain development and
      homeostasis. Mice died approximately 3 weeks after birth. These results imply
      that GSLs are essential for brain maturation.

PMID- 16109771
TI  - Dissecting the genetic complexity of human 6p deletion syndromes by using a
      region-specific, phenotype-driven mouse screen.
AB  - Monosomy of the human chromosome 6p terminal region results in a variety of
      congenital malformations that include brain, craniofacial, and organogenesis
      abnormalities. To examine the genetic basis of these phenotypes, we have carried
      out an unbiased functional analysis of the syntenic region of the mouse genome
      (proximal Mmu13). A genetic screen for recessive mutations in this region
      recovered thirteen lines with phenotypes relevant to a variety of clinical
      conditions. These include two loci that cause holoprosencephaly, two that
      underlie anophthalmia, one of which also contributes to other craniofacial
      abnormalities such as microcephaly, agnathia, and palatogenesis defects, and one
      locus responsible for developmental heart and kidney defects. Analysis of
      heterozygous carriers of these mutations shows that a high proportion of these
      loci manifest with behavioral activity and sensorimotor deficits in the
      heterozygous state. This finding argues for the systematic, reciprocal phenotypic
      assessment of dominant and recessive mouse mutants. In addition to providing a
      resource of single gene mutants that model 6p-associated disorders, the work
      reveals unsuspected genetic complexity at this region. In particular, many of the
      phenotypes associated with 6p deletions can be elicited by mutation in one of a
      number of genes. This finding implies that phenotypes associated with contiguous
      gene deletion syndromes can result not only from dosage sensitivity of one gene
      in the region but also from the combined effect of monosomy for multiple genes
      that function within the same biological process.

PMID- 16109773
TI  - Insertional mutagenesis identifies genes that promote the immortalization of
      primary bone marrow progenitor cells.
AB  - Retroviruses can induce hematopoietic disease via insertional mutagenesis of
      cancer genes and provide valuable molecular tags for cancer gene discovery. Here
      we show that insertional mutagenesis can also identify genes that promote the
      immortalization of hematopoietic cells, which normally have only limited self
      renewal. Transduction of mouse bone marrow cells with replication-incompetent
      murine stem cell virus (MSCV) expressing only neo, followed by serial passage in
      liquid culture containing stem cell factor (SCF) and interleukin-3 (IL-3),
      produced immortalized immature myeloid cell lines with neutrophil and macrophage
      differentiation potential in about 50% of the infected cultures. More than half
      of the lines have MSCV insertions at Evi1 or Prdm16. These loci encode
      transcription factor homologs and are validated human myeloid leukemia genes.
      Integrations are located in intron 1 or 2, where they promote expression of
      truncated proteins lacking the PRDI-BF1-RIZ1 homologous (PR) domain, similar to
      what is observed in human leukemias with EVI1 or PRDM16 mutations. Evi1
      overexpression alone appears sufficient to immortalize immature myeloid cells and
      does not seem to require any other cooperating mutations. Genes identified by
      insertional mutagenesis by their nature could also be involved in immortalization
      of leukemic stem cells, and thus represent attractive drug targets for treating
      cancer.

PMID- 16109772
TI  - Phosphorylated FADD induces NF-kappaB, perturbs cell cycle, and is associated
      with poor outcome in lung adenocarcinomas.
AB  - In an effort to identify a clinical biomarker for lung cancer, we used cDNA
      microarray and 2D protein analyses to demonstrate that increased Fas-associated
      death domain (FADD) mRNA and protein were significantly associated with poor
      survival. Analyses of copy number and sequence of the FADD gene in 24 independent
      tumors ruled out the existence of an amplified and/or mutated FADD gene in
      aggressive lung cancers. Immunohistochemistry-based tissue microarray analysis
      showed that nuclear localization of FADD and elevation of the phosphorylated form
      of FADD (p-FADD) correlated with poor outcome (P = 0.003). Tumors with increased
      p-FADD expression showed elevated NF-kappaB (P = 0.004) activation, a frequent
      molecular alteration associated with tumorigenesis and metastasis in a variety of
      cancers. To provide a link between p-FADD and NF-kappaB, cell culture studies
      demonstrated that overexpression of p-FADD leads to an increase in NF-kappaB
      activity and a decrease in the number of cells in the G2 phase of the cell cycle,
      compared with cells expressing the nonphosphorylatable form of FADD or the vector
      control. Furthermore, cDNA microarray analyses of lung tumor samples showed that
      increased levels of FADD transcripts were significantly correlated with
      overexpression of cyclins D1 (P < 0.01) and B1 (P < 0.01), genes that are
      involved in the regulation of cell cycle progression and are inducible by NF
      kappaB. These studies demonstrate that induction of NF-kappaB activity and its
      effects on cell-cycle progression may represent a molecular basis underlying the
      aggressive tumor behavior associated with elevated p-FADD expression in lung
      adenocarcinoma.

PMID- 16109774
TI  - Variegation of the phenotype induced by the Gata1low mutation in mice of
      different genetic backgrounds.
AB  - All mice harboring the X-linked Gata1low mutation in a predominantly CD1
      background are born anemic and thrombocytopenic. They recover from anemia at 1
      month of age but remain thrombocytopenic all their life and develop
      myelofibrosis, a syndrome similar to human idiopathic myelofibrosis, at 12
      months. The effects of the genetic background on the myelofibrosis developed by
      Gata1low mice was assessed by introducing the mutation, by standard genetic
      approaches, in the C57BL/6 and DBA/2 backgrounds and by analyzing the phenotype
      of the different mutants at 12 to 13 (by histology) and 16 to 20 (by
      cytofluorimetry) months of age. Although all the Gata1low mice developed fibrosis
      at 12 to 13 months, variegations were observed in the severity of the phenotype
      expressed by mutants of different backgrounds. In C57BL/6 mice, the mutation was
      no longer inherited in a Mendelian fashion, and fibrosis was associated with
      massive osteosclerosis. Instead, DBA/2 mutants, although severely anemic,
      expressed limited fibrosis and osteosclerosis and did not present tear-drop
      poikilocytes in blood or extramedullary hemopoiesis in liver up to 20 months of
      age. We propose that the variegation in myelofibrosis expressed by Gata1low
      mutants of different strains might represent a model to study the variability of
      the clinical picture of the human disease.

PMID- 16109775
TI  - Genetic variation in the IL-10 pathway modulates severity of acute graft-versus
      host disease following hematopoietic cell transplantation: synergism between IL
      10 genotype of patient and IL-10 receptor beta genotype of donor.
AB  - We have previously shown that the interleukin 10 (IL-10)/-592*A allele of the
      recipient is associated with less severe acute graft-versus-host disease (GVHD)
      and a lower risk of nonrelapse mortality after hematopoietic cell transplantation
      (HCT) from an HLA-identical sibling. In the present study, we examined variation
      in the IL-10 receptor beta gene as a further test of the hypothesis that the IL
      10 pathway regulates the risk of acute GVHD. A single nucleotide polymorphism
      (A/G) at cDNA position 238 of the IL-10 receptor beta gene (IL10RB/c238) was
      genotyped in 953 HC transplant recipients and their HLA-identical sibling donors.
      IL-10/-592 and IL10RB/c238 genotypes were tested for association with GVHD by
      multivariable analysis. The IL-10/-592*A allele of the recipient and
      IL10RB/c238*G allele of the donor were significantly associated with a lower risk
      of grades III-IV acute GVHD (trend P < .001 and P = .02, respectively). The donor
      IL10RB/c238*G allele provided protection among patients with the IL-10/-592 A/C
      or A/A genotypes but not among patients with the high-risk IL-10/-592 C/C
      genotype. These data suggest an interaction of the patient IL-10/-592 and donor
      IL10RB/c238 genotypes on risk of GVHD, further supporting the hypothesis that the
      IL-10 pathway plays an important role in controlling the severity of acute GVHD.

PMID- 16109776
TI  - Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association
      with other gene abnormalities and previously established gene expression
      signatures and their favorable prognostic significance.
AB  - Mutations in nucleophosmin NPM1 are the most frequent acquired molecular
      abnormalities in acute myeloid leukemia (AML). We determined the NPM1 mutation
      status in a clinically and molecularly well-characterized patient cohort of 275
      patients with newly diagnosed AML by denaturing high-performance liquid
      chromatography (dHPLC). We show that NPM1 mutations are significantly
      underrepresented in patients younger than 35 years. NPM1 mutations positively
      correlate with AML with high white blood cell counts, normal karyotypes, and fms
      like tyrosine kinase-3 gene (FLT3) internal tandem duplication (ITD) mutations.
      NPM1 mutations associate inversely with the occurrence of CCAAT/enhancer-binding
      protein-alpha (CEBPA) and NRAS mutations. With respect to gene expression
      profiling, we show that AML cases with an NPM1 mutation cluster in specific
      subtypes of AML with previously established gene expression signatures, are
      highly associated with a homeobox gene-specific expression signature, and can be
      predicted with high accuracy. We demonstrate that patients with intermediate
      cytogenetic risk AML without FLT3 ITD mutations but with NPM1 mutations have a
      significantly better overall survival (OS) and event-free survival (EFS) than
      those without NPM1 mutations. Finally, in multivariable analysis NPM1 mutations
      express independent favorable prognostic value with regard to OS, EFS, and
      disease-free survival (DFS).

PMID- 16109777
TI  - Regulation of human fetal hemoglobin: new players, new complexities.
AB  - The human globin genes are among the most extensively characterized in the human
      genome, yet the details of the molecular events regulating normal human
      hemoglobin switching and the potential reactivation of fetal hemoglobin in adult
      hematopoietic cells remain elusive. Recent discoveries demonstrate physical
      interactions between the beta locus control region and the downstream structural
      gamma- and beta-globin genes, and with transcription factors and chromatin
      remodeling complexes. These interactions all play roles in globin gene expression
      and globin switching at the human beta-globin locus. If the molecular events in
      hemoglobin switching were better understood and fetal hemoglobin could be more
      fully reactivated in adult cells, the insights obtained might lead to new
      approaches to the therapy of sickle cell disease and beta thalassemia by
      identifying specific new targets for molecular therapies.

PMID- 16109778
TI  - Enhanced TNF-alpha-induced apoptosis in Fanconi anemia type C-deficient cells is
      dependent on apoptosis signal-regulating kinase 1.
AB  - Fanconi anemia (FA) is a chromosomal instability disorder characterized by
      progressive bone marrow failure. Experimental evidence suggests that enhanced
      oxidant and myelosuppressive cytokine-mediated apoptosis of hematopoietic stem
      and progenitor cells contributes to the pathogenesis of marrow failure in FA.
      However, the molecular mechanisms responsible for the apoptotic phenotype in
      hematopoietic cells are incompletely understood. Recent data in Fancc-/- murine
      embryonic fibroblasts (MEFs) implicate increased oxidant-induced apoptotic
      signaling through the redox-dependent protein, apoptosis signal-regulating kinase
      1 (Ask1). Here, we examined whether altered Ask1 signaling participated in the
      proapoptotic phenotype of primary Fancc-/- MEFs and hematopoietic progenitors
      treated with the myelosuppressive cytokine tumor necrosis factor-alpha (TNF
      alpha). Our data indicate that TNF-alpha induces hyperactivation of Ask1 and the
      downstream effector p38 in Fancc-/- MEFs. In addition,Ask1 inactivation in Fancc
      /- MEFs and hematopoietic progenitors restored survival to wild-type (WT) levels
      in the presence of TNF-alpha. Furthermore, targeting the Ask1 pathway by using
      either antioxidants or a p38 inhibitor protected Fancc-/- MEFs and c-kit+ cells
      from TNF-alpha-induced apoptosis. Collectively, these data argue that the
      predisposition of Fancc-/- hematopoietic progenitors to apoptosis is mediated in
      part through altered redox regulation and Ask1 hyperactivation.

PMID- 16109779
TI  - Local tumor invasiveness is more predictive of survival than International
      Prognostic Index in stage I(E)/II(E) extranodal NK/T-cell lymphoma, nasal type.
AB  - This study was launched to determine the prognostic significance of local tumor
      invasiveness (LTI) in 114 patients diagnosed with stage I(E)/II(E) extranodal
      natural killer (NK)/T-cell lymphoma, nasal type (NTCL). LTI was defined as bony
      invasion or destruction or tumor invasion of the skin. Complete remission (CR),
      overall survival (OS), and disease-free survival (DFS) were compared between each
      group according to LTI, Ann Arbor stage, and International Prognostic Index
      (IPI). LTI was observed in 23 patients. Using multivariate analysis, factors
      associated with low probability of CR were the presence of LTI (P < .001), the
      presence of B symptoms (P = .003), and single-modality chemotherapy (P = .045).
      The presence of LTI (relative risk [RR] = 8.4, 95% confidence interval [CI] 3.9
      17.9; P < .001) and high IPI score (RR = 2.8, 95% CI 1.2-6.8; P = .019) were also
      predictive of OS. The presence of LTI (RR = 7.3, 95% CI 3.2-16.5; P < .001) was
      an independently significant factor for reduced DFS. Ann Arbor staging system did
      not predict CR, OS, or DFS but IPI did have predictive power with regard to
      survival outcome. LTI is the most important prognostic factor in predicting low
      probability of CR and reduced OS and DFS in nasal stage I(E)/II(E) NTCL.

PMID- 16109780
TI  - Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients
      receiving antithrombotic prophylaxis with fondaparinux or enoxaparin.
AB  - Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating IgG
      antibodies that recognize platelet factor 4 (PF4) bound to heparin.
      Immunogenicity of heparins differs in that unfractionated heparin (UFH) induces
      more anti-PF4/heparin antibodies than low-molecular-weight heparin (LMWH) and UFH
      also causes more HIT. Fondaparinux, a synthetic anticoagulant modeled after the
      antithrombin-binding pentasaccharide, is believed to be nonimmunogenic. We tested
      2726 patients for anti-PF4/heparin antibodies after they were randomized to
      receive antithrombotic prophylaxis with fondaparinux or LMWH (enoxaparin)
      following hip or knee surgery. We also evaluated in vitro cross-reactivity of the
      IgG antibodies generated against PF4 in the presence of UFH, LMWH, danaparoid, or
      fondaparinux. We found that anti-PF4/heparin antibodies were generated at similar
      frequencies in patients treated with fondaparinux or enoxaparin. Although
      antibodies reacted equally well in vitro against PF4/UFH and PF4/LMWH, and
      sometimes weakly against PF4/danaparoid, none reacted against PF4/fondaparinux,
      including even those sera obtained from patients who formed antibodies during
      fondaparinux treatment. At high concentrations, however, fondaparinux inhibited
      binding of HIT antibodies to PF4/polysaccharide, indicating that PF4/fondaparinux
      interactions occur. No patient developed HIT. We conclude that despite similar
      immunogenicity of fondaparinux and LMWH, PF4/fondaparinux, but not PF4/LMWH, is
      recognized poorly by the antibodies generated, suggesting that the risk of HIT
      with fondaparinux likely is very low.

PMID- 16109781
TI  - Effective therapy of human lymphoma xenografts with a novel recombinant
      ribonuclease/anti-CD74 humanized IgG4 antibody immunotoxin.
AB  - Ranpirnase (Rap) is a cytotoxic ribonuclease (RNase) isolated from frog oocytes.
      Here we describe high antitumor activity of a novel immunotoxin, 2L-Rap-hLL1
      gamma4P, composed of 2 Rap molecules, each fused to the N terminus of the light
      chain of hLL1, an internalizing anti-CD74 humanized antibody. To reduce unwanted
      side effects, the constant region of hLL1 was changed from gamma1 to gamma4 and
      further to gamma4P by replacing serine228 to proline to prevent the formation of
      a half immunoglobulin G (IgG) common for IgG4. In vitro, 2L-Rap-hLL1-gamma4P
      retained RNase activity, specific binding to CD74, and was significantly more
      potent against CD74+ cell lines (Daudi, Raji, and MC/CAR) than naked hLL1. In
      vivo, the pharmacokinetic profile of 2L-Rap-hLL1-gamma4P was similar to that of
      naked hLL1. The maximum tolerated dose of 2L-Rap-hLL1-gamma4P in severe combined
      immunodeficient mice (SCID) or BALB/c mice was 50 microg per mouse. In Raji and
      Daudi Burkitt lymphoma xenograft models, treatment with a single 5 to 50 microg
      dose of 2L-Rap-hLL1-gamma4P, given as early or delayed treatment, resulted in
      cures of most animals. Treatment with 2L-Rap-hLL1-gamma4P was significantly
      better than all controls, including saline, naked hLL1, and nonspecific
      immunotoxin. In conclusion, 2L-Rap-hLL1-gamma4P demonstrated excellent in vitro
      and in vivo efficacy and thus merits further consideration as a therapeutic for
      CD74+ tumors.

PMID- 16109782
TI  - Clinical characteristics and outcome of children with Down syndrome and acute
      lymphoblastic leukemia: a Children's Cancer Group study.
AB  - We assessed the outcome of children with Down syndrome (DS) and acute
      lymphoblastic leukemia (ALL) receiving contemporary risk-based therapy by
      evaluating clinical and biologic features and outcome of children with ALL, with
      or without DS, enrolled in Children's Cancer Group (CCG) protocols between 1983
      and 1995. Comparison of characteristics of children with ALL with (ALL-DS; n =
      179) or without (ALL-NDS; n = 8268) DS showed no differences in initial white
      blood cell (WBC) count, central nervous system disease, and risk group. Children
      with ALL-DS did not present with unfavorable translocations and were older than 1
      year of age at diagnosis with ALL. Event-free (56% vs 74%; P < .001) and disease
      free (55% vs 73%; P < .001) survival at 10 years was significantly lower in the
      standard-risk ALL-DS population compared with ALL-NDS, but not in high-risk ALL
      DS population (event-free survival, 62% vs 59%; P = .9; disease-free survival,
      64% vs 59%; P = .9), and these differences persisted regardless of treatment era
      (early era [1983-1989] vs recent era [1989-1995]). Multivariate analysis revealed
      that presence of DS demonstrated an independent significant adverse prognostic
      effect for the standard-risk population, but not for the high-risk patients.
      These results suggest that intensification of therapy for patients with ALL-DS is
      needed to maintain outcome comparable with those of ALL-NDS patients.

PMID- 16109783
TI  - Electrophysiological characterization of pancreatic islet cells in the mouse
      insulin promoter-green fluorescent protein mouse.
AB  - We recently reported a transgenic [mouse insulin promoter (MIP)-green fluorescent
      protein (GFP)] mouse in which GFP expression is targeted to the pancreatic islet
      beta-cells to enable convenient identification of beta-cells as green cells. The
      GFP-expressing beta-cells of the MIP-GFP mouse were functionally
      indistinguishable from beta-cells of normal mice. Here we characterized the ionic
      channel properties and exocytosis of MIP-GFP mouse islet beta- and alpha-cells.
      Beta-cells displayed delayed rectifying K+ and high-voltage-activated Ca2+
      channels and exhibited Na+ currents only at hyperpolarized holding potential.
      Alpha-cells were nongreen and had both A-type and delayed rectifier K+ channels,
      both low-voltage-activated and high-voltage-activated Ca2+ channels, and
      displayed Na+ currents readily at -70 mV holding potential. Alpha-cells had ATP
      sensitive K+ channel (KATP) channel density as high as that in beta-cells, and,
      surprisingly, alpha-cell KATP channels were more sensitive to ATP inhibition
      (IC50=0.16+/-0.03 mM) than beta-cell KATP channels (IC50=0.86+/-0.10 mM). Whereas
      alpha-cells were rather uniform in size [2-4.5 picofarad (pF)], beta-cells varied
      vastly in size (2-12 pF). Of note, small beta-cells (<4.5 pF) showed little
      exocytosis, whereas medium beta-cells (5-8 pF) exhibited vigorous exocytosis, but
      large beta-cells (>8 pF) had weaker exocytosis. We found no correlation between
      beta-cell size and their Ca2+ channel density, suggesting that Ca2+ influx may
      not be the cause of the heterogeneity in exocytotic responses. The MIP-GFP mouse
      therefore offers potential to further explore the functional heterogeneity in
      beta-cells of different sizes. The MIP-GFP mouse islet is therefore a reliable
      model to efficiently examine alpha-cell and beta-cell physiology and should
      greatly facilitate examination of their pathophysiology when the MIP-GFP mice are
      crossed with diabetic models.

PMID- 16109784
TI  - GLUT8 subcellular localization and absence of translocation to the plasma
      membrane in PC12 cells and hippocampal neurons.
AB  - GLUT8 is a high-affinity glucose transporter present mostly in testes and a
      subset of brain neurons. At the cellular level, it is found in a poorly defined
      intracellular compartment in which it is retained by an N-terminal dileucine
      motif. Here we assessed GLUT8 colocalization with markers for different cellular
      compartments and searched for signals, which could trigger its cell surface
      expression. We showed that when expressed in PC12 cells, GLUT8 was located in a
      perinuclear compartment in which it showed partial colocalization with markers
      for the endoplasmic reticulum but not with markers for the trans-Golgi network,
      early endosomes, lysosomes, and synaptic-like vesicles. To evaluate its presence
      at the plasma membrane, we generated a recombinant adenovirus for the expression
      of GLUT8 containing an extracellular myc epitope. Cell surface expression was
      evaluated by immunofluorescence microscopy of transduced PC12 cells or primary
      hippocampal neurons exposed to different stimuli. Those included substances
      inducing depolarization, activation of protein kinase A and C, activation or
      inhibition of tyrosine kinase-linked signaling pathways, glucose deprivation, AMP
      activated protein kinase stimulation, and osmotic shock. None of these stimuli
      induced GLUT8 cell surface translocation. Furthermore, when GLUT8myc was
      cotransduced with a dominant-negative form of dynamin or GLUT8myc-expressing PC
      12 cells or neurons were incubated with an anti-myc antibody, no evidence for
      constitutive recycling of the transporter through the cell surface could be
      obtained. Thus, in cells normally expressing it, GLUT8 was associated with a
      specific intracellular compartment in which it may play an as-yet-uncharacterized
      role.

PMID- 16109785
TI  - Hypoxia-inducible factor-1-mediated activation of stanniocalcin-1 in human cancer
      cells.
AB  - Stanniocalcin-1 (STC1) is an endocrine hormone originally discovered in the
      corpuscles of Stannius, endocrine glands on kidneys of bony fishes, and also has
      been identified in mammals. The mammalian STC1 gene is widely expressed in
      various tissues and appears to be involved in diverse biological processes. There
      is growing evidence to suggest that altered patterns of gene expression have a
      role in human cancer development. Recently STC1 has been identified as a
      stimulator of mitochondrial respiration and has been hypothesized to be
      functionally related to the Warburg effect, of which hypoxia-inducible factor
      (HIF)-1 plays a key role in reprogramming tumor metabolism. This prompted us to
      examine the involvement of HIF-1 in the regulation of STC1 expression in tumor
      hypoxia. Our data reveal that hypoxia can stimulate STC1 gene expression in
      various human cancer cell lines, including those derived from colon carcinomas,
      nasopharyngeal cancer (CNE-2, HONE-1, HK-1), and ovarian cancer (CaOV3, OVCAR3,
      SKOV3). By far, the greatest response was observed in CNE-2 cells. In further
      studies on CNE-2 cells, desferrioxamine, cobalt chloride, and O(2) depletion all
      increased HIF-1alpha protein and STC1 mRNA levels. Desferrioxamine treatment,
      when coupled with Fe replenishment, abolished these effects. RNA interference
      studies further confirmed that endogenous HIF-1alpha was a key factor in hypoxia
      induced STC1 expression. The ability of vascular endothelial growth factor to
      stimulate STC1 expression in CNE-2 cells was comparatively low. Collectively, the
      present findings provide the first evidence of HIF-1 regulation of STC1
      expression in human cancer cells. The studies have implications as to the role of
      STC1 in hypoxia induced adaptive responses in tumor cells.

PMID- 16109786
TI  - C-type natriuretic Peptide down-regulates expression of its cognate receptor in
      rat aortic smooth muscle cells.
AB  - The C-type natriuretic (CNP) peptide signals through the type B natriuretic
      peptide receptor (NPR-B) in vascular smooth muscle cells to activate the
      particulate guanylyl cyclase activity intrinsic to that receptor and raise
      cellular cyclic GMP levels. In the present study, we demonstrate that CNP down
      regulates the expression of this receptor leading to a reduction in NPR-B
      activity. Pretreatment of rat aortic smooth muscle cells with CNP reduces NPR-B
      activity, NPR-B protein levels, NPR2 (NPR-B gene) mRNA levels, and NPR2 promoter
      activity. The decrease in NPR2 promoter activity is dependent on DNA sequence
      present between -441 and -134 relative to the transcription start site. The
      reduction in NPR2 gene expression appears to operate through generation of cyclic
      GMP. 8-Bromo cyclic GMP, a membrane-permeable cyclic GMP analog, reduced NPR2
      mRNA levels and NPR2 promoter activity. Atrial natriuretic peptide, which signals
      through the type A natriuretic peptide receptor (NPR-A) to increase cyclic GMP
      levels in these cells, also reduced NPR-B mRNA levels and inhibited NPR-B
      promoter activity; however, this inhibition was not additive with that produced
      by CNP, implying that the two ligands traffic over a common signal transduction
      pathway. This report provides the first documentation that CNP is capable of
      autoregulating the expression of its cognate receptor.

PMID- 16109787
TI  - Regulation of the endothelin/endothelin receptor system by interleukin-1{beta} in
      human myometrial cells.
AB  - Proinflammatory cytokines produced at the fetomaternal interface, such as IL
      1beta, have been implicated in preterm and term labor. The present study was
      performed to evaluate the influence of IL-1beta on the endothelin (ET)/ET
      receptor system in human myometrial cells. We report that myometrial cells under
      basal conditions not only respond to but also secrete ET-1, one of the main
      regulators of uterine contractions. Prolonged exposure of the cells to IL-1beta
      led to a decrease in prepro-ET-1 and ET-3 mRNA correlated with a decrease in
      immunoreactive ET-1 and ET-3 levels in the culture medium. Whereas ETA receptor
      expression at both protein and mRNA levels was not affected by IL-1beta
      treatment, we demonstrated an unexpected predominance of the ETB receptor subtype
      under this inflammatory condition. Whereas the physiological function of ETB
      remains unclear, we confirmed that only ETA receptors mediate ET-1-induced
      myometrial cell contractions under basal conditions. By contrast, prolonged
      exposure of the cells to IL-1beta abolished the contractile effect induced by ET
      1. Such a regulation of IL-1beta on the ET release and the balance of ETA to ETB
      receptors leading to a loss of ET-1-induced myometrial cell contractions suggest
      that complex regulatory mechanisms take place to constraint the onset of
      infection-induced premature contractions.

PMID- 16109788
TI  - Protein kinase A-dependent synergism between GATA factors and the nuclear
      receptor, liver receptor homolog-1, regulates human aromatase (CYP19) PII
      promoter activity in breast cancer cells.
AB  - Cancers, including that of the breast, are the result of multiple contributing
      factors including aberrant gene expression. Indeed, the CYP19 gene encoding P450
      aromatase, the key enzyme for estrogen biosynthesis, is up-regulated in breast
      tumors predominantly via the cAMP-responsive gonad-type PII promoter, ultimately
      leading to increased intratumoral estrogen production and tumor growth. Thus,
      identifying the molecular factors involved in aromatase PII promoter regulation
      is essential for our understanding and treatment of the disease. Because we have
      previously shown activity of the murine aromatase PII promoter to be markedly up
      regulated by GATA factors with respect to the gonads, we hypothesized that GATA
      factors are also key determinants of human PII promoter-driven aromatase
      transcription in breast tumors. We now show that GATA3 and GATA4 are indeed
      expressed in several breast cancer cells lines. Consistent with the cAMP
      dependence of the PII promoter, activation elicited by GATA3 or GATA4 alone and
      the striking synergism between GATA3 or GATA4 and the nuclear receptor liver
      receptor homolog (LRH)-1 was intimately linked to forskolin treatment or
      overexpression of protein kinase A (PKA) catalytic subunit. PKA-mediated
      phosphorylation increases the interaction between GATA3 and LRH-1 and the
      requirement for PKA in aromatase PII promoter stimulation involves at least three
      specific amino acid residues: GATA3 Ser308, GATA4 Ser261, and LRH-1 Ser469.
      Finally, we show that the human LRH-1 promoter is itself a target for GATA
      factors. Thus, taken together, our results suggest that GATA factors likely
      contribute to aberrant aromatase expression in breast tumors through two
      distinct, yet complementary mechanisms.

PMID- 16109789
TI  - The antiarrhythmic peptide analog rotigaptide (ZP123) stimulates gap junction
      intercellular communication in human osteoblasts and prevents decrease in femoral
      trabecular bone strength in ovariectomized rats.
AB  - Gap junctions play an important role in bone development and function, but the
      lack of pharmacological tools has hampered the gap junction research. The
      antiarrhythmic peptides stimulate gap junction communication between
      cardiomyocytes, but effects in noncardiac tissue are unknown. The purpose of this
      study was to examine whether antiarrhythmic peptides, which are small peptides
      increasing gap junctional conductivity, show specific binding to osteoblasts and
      investigate the effect of the stable analog rotigaptide (ZP123) on gap junctional
      intercellular communication in vitro and on bone mass and strength in vivo. Cell
      coupling and calcium signaling were assessed in vitro on human, primary,
      osteoblastic cells. In vivo effects of rotigaptide on bone strength and density
      were determined 4 wk after ovariectomy in rats treated with either vehicle, sc
      injection twice daily (300 nmol per kilogram body weight) or by continuous ip
      infusion (158 nmol per kilogram body weight per day). During metabolic stress, a
      high affinity-binding site (KD=0.1 nM) with low density (15 fmol/mg protein) for
      [125I]di-I-AAP10 was demonstrated. During physiological conditions, specific
      binding sites for [125I]AAP10 could not be shown. Studies of the effects of
      rotigaptide on propagation of intercellular calcium waves and cell-to-cell
      coupling demonstrated that 10 nM rotigaptide produced a small increase in
      intercellular communication during physiological conditions (+4.5+/-1.6% vs.
      vehicle; P<0.05). During conditions with metabolic stress, 10 nM rotigaptide
      produced an increase in coupling measured by both methods. Four weeks after
      ovariectomy, bone strength of the femoral head was reduced by 20% in vehicle
      treated ovariectomized rats, which was completely prevented in both rotigaptide
      treated groups. Rotigaptide also prevented decreases in bone mineral. We conclude
      that the stable analog rotigaptide increases gap junctional communication in
      osteoblasts in vitro and preferably during conditions with metabolic stress.
      Rotigaptide further prevents ovariectomy-induced bone loss in vivo. Thus, gap
      junction modulation may be a promising new target for osteoporosis therapy.

PMID- 16109792
TI  - Teaching glucocorticoid negative feedback and adrenocortical regulation using a
      classic paper by Dr. Dwight Ingle.
AB  - The American Physiological Society (APS) Legacy Project and its accompanying
      Essays on APS Classic Papers have allowed the scientific community on-line access
      to the entire collection of APS publications since their inception in 1898
      (http://www.the-aps.org/publications/legacy/ and http://www.the
      aps.org/publications/classics/). The availability of the classic physiological
      studies provides a unique teaching opportunity. The classic paper of Dr. Dwight
      Ingle represents just such a study. Dr. Ingle demonstrated that, using only
      purified extracts of the pituitary (ACTH) and adrenal cortex (corticosterone) and
      hypophysectomized rats, he could establish several of the basic principles of the
      control of adrenal function and glucocorticoid negative feedback that are now
      standard teaching material in endocrinology. An annotated figure from Dr. Ingle's
      paper is provided, which, when assigned to undergraduate or graduate students,
      will allow discovery learning. Furthermore, the brilliance and imagination of the
      physiologists of the last century are highlighted, which allows an appreciation
      of the seminal work of our predecessors.

PMID- 16109793
TI  - The evolving role of animal laboratories in physiology instruction.
AB  - Laboratory exercises are intended to illustrate concepts and add an active
      learning component to courses. Since the 1980s, there has been a decline in
      animal laboratories offered in conjunction with medical physiology courses. The
      most important single reason for this is cost, but other contributing factors
      include the development of computer simulations, changes in medical education,
      and pressure from antivivisectionists. Unfortunately, the elimination of animal
      laboratories has occurred with relatively little consideration of the educational
      impact of this change. Although computer simulations are considered effective in
      helping students acquire basic physiological concepts, there is evidence some
      students acquire a more thorough understanding of the material through the more
      advanced and challenging experience of an animal laboratory. The fact that such
      laboratories offer distinct educational advantages should be taken into account
      when courses are designed.

PMID- 16109794
TI  - The power of real-time PCR.
AB  - In recent years, real-time polymerase chain reaction (PCR) has emerged as a
      robust and widely used methodology for biological investigation because it can
      detect and quantify very small amounts of specific nucleic acid sequences. As a
      research tool, a major application of this technology is the rapid and accurate
      assessment of changes in gene expression as a result of physiology,
      pathophysiology, or development. This method can be applied to model systems to
      measure responses to experimental stimuli and to gain insight into potential
      changes in protein level and function. Thus physiology can be correlated with
      molecular events to gain a better understanding of biological processes. For
      clinical molecular diagnostics, real-time PCR can be used to measure viral or
      bacterial loads or evaluate cancer status. Here, we discuss the basic concepts,
      chemistries, and instrumentation of real-time PCR and include present
      applications and future perspectives for this technology in biomedical sciences
      and in life science education.

PMID- 16109795
TI  - How to engage medical students in chronobiology: an example on autorhythmometry.
AB  - This contribution describes a new laboratory experience that improves medical
      students' learning of chronobiology by introducing them to basic chronobiology
      concepts as well as to methods and statistical analysis tools specific for
      circadian rhythms. We designed an autorhythmometry laboratory session where
      students simultaneously played the role of researchers and experimental subjects.
      During this session, which lasted 24 h, students recorded their own arterial
      pressure, heart rate, oral temperature, forced expiratory flow, glucose
      tolerance, muscular strength, reaction time, and sensorimotor coordination at
      regular intervals and also took the Horne and Ostberg test, after which they
      analyzed their own data. Furthermore, to gather information from subjects under
      normal sleep and eating schedules, some students acquired data at home. To guide
      and help students with their work, a dedicated web page was implemented with
      scientific references, cosinor analysis software, and other valuable information.
      All these "raw" data were combined into a single database that students could use
      to evaluate whatever aspect of the data they seemed fit. A number of suggestions
      were offered to them as guidance. Students were then instructed to write a
      scientific article on the subject they had chosen. The experience was highly
      rewarding for both instructors and students alike. In view of the high level of
      absenteeism in Spanish universities and the fact that 93% of the students
      attended the exam and 95% of these passed, the experience was considered a great
      success.

PMID- 16109796
TI  - An experimental approach to the fundamental principles of hemodynamics.
AB  - An experimental model has been developed to give students hands-on experience
      with the fundamental laws of hemodynamics. The proposed experimental setup is of
      simple construction but permits the precise measurements of physical variables
      involved in the experience. The model consists in a series of experiments where
      different basic phenomena are quantitatively investigated, such as the pressure
      drop in a long straight vessel and in an obstructed vessel, the transition from
      laminar to turbulent flow, the association of vessels in vascular networks, or
      the generation of a critical stenosis. Through these experiments, students
      acquire a direct appreciation of the importance of the parameters involved in the
      relationship between pressure and flow rate, thus facilitating the comprehension
      of more complex problems in hemodynamics.

PMID- 16109797
TI  - Prevalence of blood circulation misconceptions among prospective elementary
      teachers.
AB  - Research shows that misconceptions about human blood circulation and gas exchange
      persist across grade levels. The purpose of this study was twofold: 1) to
      investigate the prevalence and persistence of blood circulation misconceptions
      among prospective elementary teachers and 2) to evaluate the effectiveness of
      learning activities for discovering what students know and can explain about
      blood circulation and lung function. The context was an undergraduate
      introduction to biology course taught by two professors across three semesters at
      a state university. Independent reviewers identified five categories of erroneous
      ideas about blood circulation. Many categories still presented problems to
      students at the end of the course: 70% of prospective elementary teachers did not
      understand the dual blood circulation pathway, 33% were confused about blood
      vessels, 55% had wrong ideas about gas exchange, 19% had trouble with gas
      transport and utilization, and 20% did not understand lung function. Results show
      that an interview about a drawing as a final exam was significantly better at
      revealing different errors and a higher frequency of erroneous ideas compared
      with an essay exam. There is an urgent need for instructional tools to help
      undergraduate students realize the discrepancies between their own ideas about
      blood circulation and those of the scientific community.

PMID- 16109798
TI  - How to be a bad teacher.

PMID- 16109800
TI  - Open-book tests and student-authored exam questions as useful tools to increase
      critical thinking.

PMID- 16109801
TI  - Merit-based rearrangement of students for better interactions.

PMID- 16109802
TI  - Leptin downregulates ghrelin levels in streptozotocin-induced diabetic mice.
AB  - Ghrelin, an orexigenic peptide produced in the stomach, is increased in
      streptozotocin (STZ)-induced diabetic (DM) mice. This study clarifies the
      regulation of ghrelin levels by leptin in STZ-DM mice. STZ-DM mice had higher
      plasma ghrelin concentrations and greater ghrelin mRNA expression than control
      mice. Changes in ghrelin levels were dose dependently attenuated by the
      subcutaneous injection of leptin (0-27 nmol x kg(-1) x day(-1) over 7 days).
      Leptin treatment also partially reversed the hyperphagia and hyperglycemia
      observed in STZ-DM mice, but not the hypoinsulinemia, and there was a decrease in
      plasma ghrelin concentrations and ghrelin mRNA levels compared with STZ-LEP pair
      fed mice. These results indicate that leptin treatment partially reverses
      elevated plasma ghrelin levels in STZ-DM mice independent of food intake and
      insulin, and suggest that hypoleptinemia in STZ-DM mice upregulates ghrelin.

PMID- 16109803
TI  - Effect of renal medullary H2O2 on salt-induced hypertension and renal injury.
AB  - Dahl salt-sensitive (SS) and consomic, salt-resistant SS-13(BN) rats possess
      substantial differences in blood pressure salt-sensitivity even with highly
      similar genetic backgrounds. The present study examined whether increased
      oxidative stress, particularly H2O2, in the renal medulla of SS rats contributes
      to these differences. Blood pressure was measured using femoral arterial
      catheters in three groups of rats: 1) 12-wk-old SS and consomic SS-13(BN) rats
      fed a 0.4% NaCl diet, 2) SS rats fed a 4% NaCl diet and chronically infused with
      saline or catalase (6.9 microg x kg(-1) x min(-1)) directly into the renal
      medulla, and 3) SS-13(BN) fed high salt (4%) and infused with saline or H2O2 (347
      nmol x kg(-1) x min(-1)) into the renal medullary interstitium. After chronic
      blood pressure measurements, renal medullary interstitial H2O2 concentration
      ([H2O2]) was collected by microdialysis and analyzed with Amplex red. Blood
      pressure and [H2O2] were both significantly higher in SS (126 +/- 3 mmHg and 145
      +/- 17 nM, respectively) vs. SS-13(BN) rats (116 +/- 2 mmHg and 56 +/- 14 nM) fed
      a 0.4% diet. Renal interstitial catalase infusion significantly decreased [H2O2]
      (96 +/- 41 vs. 297 +/- 52 nM) and attenuated the hypertension (146 +/- 2 mmHg
      catalase vs. 163 +/- 4 mmHg saline) in SS rats after 5 days of high salt (4%).
      H2O2 infused into the renal medulla of consomic SS-13(BN) fed high salt (4%) for
      7 days accentuated the salt sensitivity (145 +/- 2 mmHg H2O2 vs. 134 +/- 1 mmHg
      saline). [H2O2] was also increased in the treated group (83 +/- 1 nM H2O2 vs. 44
      +/- 9 nM saline). These data show that medullary production of H2O2 may
      contribute to salt-induced hypertension in SS rats and that chromosome 13 of the
      Brown Norway contains gene(s) that protect against renal medullary oxidant
      stress.

PMID- 16109804
TI  - Differential regulation of transient receptor potential melastatin 6 and 7 cation
      channels by ANG II in vascular smooth muscle cells from spontaneously
      hypertensive rats.
AB  - Intracellular Mg2+ depletion has been implicated in vascular dysfunction in
      hypertension. We demonstrated that transient receptor potential melastatin 7
      (TRPM7) cation channels mediate Mg2+ influx in VSMCs. Whether this plays a role
      in [Mg2+]i deficiency in hypertension is unclear. Here, we tested the hypothesis
      that downregulation of TRPM7 and its homologue TRPM6 is associated with reduced
      [Mg2+]i and that ANG II negatively regulates TRPM6/7 in vascular smooth muscle
      cells (VSMCs) from spontaneously hypertensive rats (SHR). Cultured VSMCs from
      Wistar Kyoto (WKY) and SHR were studied. mRNA and protein expression of TRPM6 and
      TRPM7 were assessed by RT-PCR and immunoblotting, respectively. Translocation of
      annexin-1, specific TRPM7 substrate, was measured as an index of TRPM7
      activation. [Mg2+]i was determined using mag fura-2. VSMCs from WKY and SHR
      express TRPM6 and TRPM7. Basal TRPM6 expression was similar in WKY and SHR, but
      basal TRPM7 content was lower in VSMCs from SHR vs. WKY. This was associated with
      significantly reduced [Mg2+]i in SHR cells (P < 0.01). ANG II time-dependently
      increased TRPM6 expression, with similar responses in WKY and SHR. ANG II
      significantly increased TRPM7 expression in WKY (P < 0.05), but not in SHR.
      Annexin-1 translocation was reduced 1.5-2-fold in SHR vs. WKY. Our findings
      demonstrate that TRPM6 and TRPM7 are differentially regulated in VSMCs from SHR
      and WKY. Whereas TRPM6 is unaltered in SHR, expression of TRPM7 is blunted. This
      was associated with attenuated annexin-1 translocation and decreased VSMC [Mg2+]i
      in SHR. Downregulation of TRPM7, but not TRPM6, may play a role in altered Mg2+
      homeostasis in VSMCs from SHR.

PMID- 16109805
TI  - Glial-specific ablation of angiotensinogen lowers arterial pressure in renin and
      angiotensinogen transgenic mice.
AB  - Angiotensinogen (AGT) is mainly expressed in glial cells in close proximity to
      renin-expressing neurons in the brain. We previously reported that glial-specific
      overexpression of ANG II results in mild hypertension. Here, we tested the
      hypothesis that glial-derived AGT plays an important role in blood pressure
      regulation in hypertensive mice carrying human renin (hREN) and human AGT
      transgenes under the control of their own endogenous promoters. To perform a
      glial-specific deletion of AGT, we used an AGT transgene containing loxP sites
      (hAGT(flox)), so the gene can be permanently ablated in the presence of cre
      recombinase expression, driven by the glial fibrillary acidic protein (GFAP)
      promoter. Triple transgenic mice (RAC) containing a: 1) systemically expressed
      hREN transgene, 2) systemically expressed hAGT(flox) transgene, and 3) GFAP-cre
      recombinase were generated and compared with double transgenic mice (RA) lacking
      cre-recombinase. Liver and kidney hAGT mRNA levels were unaltered in RAC and RA
      mice, as was the level of hAGT in the systemic circulation, consistent with the
      absence of cre-recombinase expression in those tissues. Whereas hAGT mRNA was
      present in the brain of RA mice (lacking cre-recombinase), it was absent from the
      brain of RAC mice expressing cre-recombinase, confirming brain-specific
      elimination of AGT. Immunohistochemistry revealed a loss of AGT immunostaining
      glial cells throughout the brain in RAC mice. Arterial pressure measured by
      radiotelemetry was significantly lower in RAC than RA mice and unchanged from
      nontransgenic control mice. These data suggest that there is a major contribution
      of glial-AGT to the hypertensive state in mice carrying systemically expressed
      hREN and hAGT genes and confirm the importance of a glial source of ANG II
      substrate in the brain.

PMID- 16109806
TI  - Intronic ANG II type 2 receptor gene polymorphism 1675 G/A modulates receptor
      protein expression but not mRNA splicing.
AB  - The X-linked ANG II type 2 receptor (AT2) is supposed to be involved in
      cardiovascular disorders. Two studies associated the A allele of the AT2 gene
      polymorphism (PM) 1675 G/A with left ventricular hypertrophy in men and coronary
      ischemia in women. Because the PM is located in the short intron 1 of the AT2
      gene within a sequence motif similar to the splice branch site consensus, we
      tested whether it might affect pre-mRNA splicing and/or modulate AT2 receptor
      expression. We first analyzed the AT2 mRNA splice pattern by RT-PCR in myocardial
      samples from 12 explanted human hearts and compared it with the respective
      genotypes. All 12 patients, 10 hemizygous males (7 A, 3 G allele carriers) and 2
      homozygous females (2 G/G allele carriers), exhibited the same myocardial AT2
      splice pattern with a relative abundance of transcript exon 1/2/3 compared with
      exon 1/3. Next, AT2 minigene constructs were cloned from both alleles, comprising
      the core promoter and the complete transcribed region up to the translation start
      codon, upstream of a luciferase reporter gene. These constructs were transfected
      into human (HT1080) and rat (PC12W) cell lines and rat vascular smooth muscle
      cells, and luciferase activities were assessed, as well as the splice patterns of
      the chimeric AT2/luciferase mRNAs. In all transfected cell types, the mRNA
      expressed from the AT2 constructs was spliced like the endogenous myocardial AT2
      mRNA. However, luciferase activities driven by the G allele construct were
      significantly higher than those expressed from the A allele. Taken together,
      these data indicate that individuals carrying the G allele may express higher
      levels of AT2 receptor protein, which may be protective during the development of
      ventricular hypertrophy and coronary ischemia.

PMID- 16109807
TI  - Influences of AT1 receptor blockade on tissue metabolism in obese men.
AB  - ANG II applied to the interstitial space influences carbohydrate and lipid
      metabolism in a tissue-specific fashion. Thus endogenous ANG II may have a tonic
      effect on tissue metabolism that could be reversed with ANG II type 1 (AT1)
      receptor blockade, particularly during adrenergic stimulation. We studied 14
      obese men. They were treated for 10 days with the AT1 receptor blocker irbesartan
      or with placebo in a double-blind and crossover fashion. At the end of each
      treatment period, we assessed skeletal muscle and adipose tissue metabolism using
      the microdialysis technique. The ethanol dilution technique was applied to follow
      changes in tissue blood flow. Measurements were obtained at baseline and during
      application of incremental isoproterenol concentrations through the microdialysis
      catheter. Blood pressure decreased from 133 +/- 3/84 +/- 3 to 128 +/- 3/79 +/- 2
      mmHg for systolic and diastolic blood, respectively (P = 0.02 and 0.006,
      respectively) with AT1 receptor blockade. Isoproterenol perfusion caused a dose
      dependent increase in dialysate glycerol in adipose tissue and in skeletal
      muscle. Irbesartan slightly reduced the isoproterenol-induced glycerol response
      in adipose tissue (P < 0.05 by ANOVA). Ethanol ratio, interstitial glucose
      supply, and lactate production in adipose tissue and skeletal muscle were similar
      with placebo and irbesartan. We conclude that AT1 receptor blockade in obese men
      does not reveal a major tonic ANG II effect on interstitial glucose supply,
      lipolysis, or glycolysis in skeletal muscle, either at rest or during beta
      adrenergic stimulation. Endogeneous ANG II may slightly increase adipose tissue
      lipolysis. The mechanism may promote the redistribution of triglycerides from
      adipose tissue toward other organs.

PMID- 16109808
TI  - Effects on sleep of microdialysis of adenosine A1 and A2a receptor analogs into
      the lateral preoptic area of rats.
AB  - Evidence suggests that adenosine (AD) is an endogenous sleep factor. The
      hypnogenic action of AD is mediated through its inhibitory A1 and excitatory A2A
      receptors. Although AD is thought to be predominantly active in the wake-active
      region of the basal forebrain (BF), a hypnogenic action of AD has been
      demonstrated in several other brain areas, including the preoptic area. We
      hypothesized that in lateral preoptic area (LPOA), a region with an abundance of
      sleep-active neurons, AD acting via A1 receptors would induce waking by
      inhibition of sleep-active neurons and that AD acting via A2A receptors would
      promote sleep by stimulating the sleep-active neurons. To this end, we studied
      the effects on sleep of an AD transport inhibitor, nitrobenzyl-thio-inosine
      (NBTI) and A1 and A2A receptor agonists/antagonists by microdialyzing them into
      the LPOA. The results showed that, in the sleep-promoting area of LPOA: 1) A1
      receptor stimulation or inhibition of AD transport by NBTI induced waking and 2)
      A2A receptor stimulation induced sleep. We also confirmed that NBTI
      administration in the wake promoting area of the BF increased sleep. The effects
      of AD could be mediated either directly or indirectly via interaction with other
      neurotransmitter systems. These observations support a hypothesis that AD
      mediated effects on sleep-wake cycles are site and receptor dependent.

PMID- 16109809
TI  - PKC and ERK are differentially involved in gonadotropin-releasing hormone-induced
      growth hormone gene expression in the goldfish pituitary.
AB  - Gonadotropin-releasing hormone (GnRH) is produced by the hypothalamus and
      stimulates the synthesis and secretion of gonadotropin hormones. In addition,
      GnRH also stimulates the production and secretion of growth hormone (GH) in some
      fish species and in humans with certain clinical disorders. In the goldfish
      pituitary, GH secretion and gene expression are regulated by two endogenous forms
      of GnRH known as salmon GnRH and chicken GnRH-II. It is well established that PKC
      mediates GnRH-stimulated GH secretion in the goldfish pituitary. In contrast, the
      signal transduction of GnRH-induced GH gene expression has not been elucidated in
      any model system. In this study, we demonstrate, for the first time, the presence
      of novel and atypical PKC isoforms in the pituitary of a fish. Moreover, our
      results indicate that conventional PKC alpha is present selectively in GH
      producing cells. Treatment of primary cultures of dispersed goldfish pituitary
      cells with PKC activators (phorbol ester or diacylglycerol analog) did not affect
      basal or GnRH-induced GH mRNA levels, and two different inhibitors of PKC
      (calphostin C and GF109203X) did not reduce the effects of GnRH on GH gene
      expression. Together, these results suggest that, in contrast to secretion,
      conventional and novel PKCs are not involved in GnRH-stimulated increases in GH
      mRNA levels in the goldfish pituitary. Instead, PD98059 inhibited GnRH-induced GH
      gene expression, suggesting that the ERK signaling pathway is involved. The
      results presented here provide novel insights into the functional specificity of
      GnRH-induced signaling and the regulation of GH gene expression.

PMID- 16109810
TI  - Apparent receptor-mediated activation of Ca2+-dependent conductive Cl- transport
      by shark-derived polyaminosterols.
AB  - The shark liver antimicrobial polyaminosterol squalamine is an angiogenesis
      inhibitor under clinical investigation as an anti-cancer agent and as a treatment
      for the choroidal neovascularization associated with macular degeneration of the
      retina. The related polyaminosterol MSI-1436 is an appetite suppressant that
      decreases systemic insulin resistance. However, the mechanisms of action of these
      polyaminosterols are unknown. We report effects of MSI-1436 on Xenopus oocytes
      consistent with the existence of a receptor for polyaminosterols. MSI-1436
      activates bidirectional, trans-chloride-independent Cl- flux in Xenopus oocytes.
      At least part of this DIDS-sensitive Cl- flux is conductive, as measured using
      two-electrode voltage-clamp and on-cell patch-clamp techniques. MSI-1436 also
      elevates cytosolic Ca2+ concentration ([Ca2+]) and increases bidirectional 45Ca2+
      flux. Activation of Cl- flux and elevation of cytosolic [Ca2+] by MSI-1436 both
      are accelerated by lowering bath Ca2+ and are not acutely inhibited by
      extracellular EGTA. Elevation of cytosolic [Ca2+] by MSI-1436 requires heparin
      sensitive intracellular Ca2+ stores. Although injected EGTA abolishes the
      increased conductive Cl- flux, that Cl- flux is not dependent on heparin
      sensitive stores. In low-bath Ca2+ conditions, several structurally related
      polyaminosterols act as strong agonists or weak agonists of conductive Cl- flux
      in oocytes. Weak agonist polyaminosterols antagonize the strong agonist, MSI
      1436, but upon addition of the conductive Cl- transport inhibitor DIDS, they are
      converted into strong agonists. Together, these properties operationally define a
      polyaminosterol receptor at or near the surface of the Xenopus oocyte, provide an
      initial description of receptor signaling, and suggest routes toward further
      understanding of a novel class of appetite suppressants and angiogenesis
      inhibitors.

PMID- 16109811
TI  - Long work hours and occupational injuries: new evidence on upstream causes.

PMID- 16109813
TI  - How "clean" is the cleaning profession?

PMID- 16109814
TI  - The impact of overtime and long work hours on occupational injuries and
      illnesses: new evidence from the United States.
AB  - AIMS: To analyse the impact of overtime and extended working hours on the risk of
      occupational injuries and illnesses among a nationally representative sample of
      working adults from the United States. METHODS: Responses from 10,793 Americans
      participating in the National Longitudinal Survey of Youth (NLSY) were used to
      evaluate workers' job histories, work schedules, and occurrence of occupational
      injury and illness between 1987 and 2000. A total of 110,236 job records were
      analysed, encompassing 89,729 person-years of accumulated working time.
      Aggregated incidence rates in each of five exposure categories were calculated
      for each NLSY survey period. Multivariate analytical techniques were used to
      estimate the relative risk of long working hours per day, extended hours per
      week, long commute times, and overtime schedules on reporting a work related
      injury or illness, after adjusting for age, gender, occupation, industry, and
      region. RESULTS: After adjusting for those factors, working in jobs with overtime
      schedules was associated with a 61% higher injury hazard rate compared to jobs
      without overtime. Working at least 12 hours per day was associated with a 37%
      increased hazard rate and working at least 60 hours per week was associated with
      a 23% increased hazard rate. A strong dose-response effect was observed, with the
      injury rate (per 100 accumulated worker-years in a particular schedule)
      increasing in correspondence to the number of hours per day (or per week) in the
      workers' customary schedule. CONCLUSIONS: Results suggest that job schedules with
      long working hours are not more risky merely because they are concentrated in
      inherently hazardous industries or occupations, or because people working long
      hours spend more total time "at risk" for a work injury. Strategies to prevent
      work injuries should consider changes in scheduling practices, job redesign, and
      health protection programmes for people working in jobs involving overtime and
      extended hours.

PMID- 16109815
TI  - Asthma, chronic bronchitis, and exposure to irritant agents in occupational
      domestic cleaning: a nested case-control study.
AB  - BACKGROUND: Women employed in domestic cleaning are at increased risk for
      symptoms of obstructive lung disease, but the agents responsible are unknown.
      AIMS: To investigate common tasks and products in occupational domestic cleaning
      in relation to respiratory morbidity. METHODS: Case-control study in domestic
      cleaning women nested within a large population based survey of women aged 30-65
      years; 160 domestic cleaning women with asthma symptoms, chronic bronchitis
      symptoms, or both and 386 without a history of respiratory symptoms were
      identified. Detailed exposures were evaluated for 40 cases who reported still
      having symptoms at the recruitment interview, and 155 controls who reported not
      having symptoms. All tasks performed and products used when cleaning houses were
      determined in a face-to-face interview. Lung function, methacholine challenge,
      and serum IgE testing were performed. Personal exposure measurements of airborne
      chlorine and ammonia were performed in a subsample. Associations between asthma,
      chronic bronchitis, and cleaning exposures were evaluated using multiple logistic
      regression analysis. RESULTS: Airborne chlorine (median level 0-0.4 ppm) and
      ammonia (0.6-6.4 ppm) were detectable during occupational domestic cleaning
      activities. Cases used bleach more frequently than controls; adjusted odds ratio
      (OR) for intermediate exposure was 3.3 (95% CI 0.9 to 11) and for high exposure
      4.9 (1.5 to 15). Other independent associations included accidental inhalation of
      vapours and gases from cleaning agents and washing dishes. These associations
      were more pronounced for cases with asthma symptoms than for those with symptoms
      of chronic bronchitis, but were not related to sensitisation to common allergens.
      CONCLUSIONS: Asthma symptoms in domestic cleaning women are associated with
      exposure to bleach and possibly other irritant agents. The public health impact
      of the use of irritant cleaning products could be widespread since the use of
      these products is common both in the workplace and at home.

PMID- 16109816
TI  - Effect of farming environment on sensitisation to allergens continues after
      childhood.
AB  - AIMS: The farming environment in childhood has been reported to decrease the risk
      of sensitisation to allergens. The purpose of the present study was to explore
      whether later exposure to a farming environment also could affect this
      sensitisation. METHODS: A population based sample of 202 women who did not live
      on a farm and 231 who did. The subjects filled in a questionnaire and underwent
      skin prick tests for several common and farming related allergens. RESULTS: The
      prevalence of sensitisation to any of the allergens was similar in the two groups
      (37.1 v 34.6% (p = NS). However, compared with women who did not live on a farm,
      the women who lived on a dairy farm showed a low prevalence of sensitisation to
      pollens (4.4 v 17.3%, p = 0.01) and cats (3.5 v 10.4%, p = 0.047). The risk of
      sensitisation to pollens and pets was lowest among women with both a childhood
      and adulthood farming environment and was dose dependently associated with
      current contact with farm animals. However, this contact increased the risk of
      sensitisation to bovine dander. CONCLUSION: The farming environment may reduce
      sensitisation to common allergens also after early childhood. However, it may
      also increase sensitisation to farm allergens.

PMID- 16109817
TI  - Sensitisation to mites in laboratory animal workers with rhinitis.
AB  - AIMS: To determine the frequency of sensitisation to mites among rhinitic
      laboratory animal workers and to clarify whether sensitisation could be
      occupational. METHODS: Skin prick tests (SPT) were performed in 40 subjects who
      were working with laboratory animals in Kuopio University research units and who
      had been referred to Kuopio University Hospital for work related rhinitis. The
      SPT panel consisted of three storage mites, two house dust mites, 11 other common
      environmental airborne allergens, latex, and 2-4 individually relevant laboratory
      animals. To determine signs of mites in animal facilities, guanine was determined
      in 22 dust samples taken from feedstuffs or bedding material used for laboratory
      animals and from rooms where these materials were stored and handled. RESULTS:
      Positive SPT results were found in 35 out of 40 workers: in 14 for storage mites,
      four for house dust mites, 25 for other common aeroallergens, as well as positive
      reactions to laboratory animals in 19 individuals. The guanine test was positive,
      indicating the presence of mite derived material in 21 out of 22 dust samples.
      CONCLUSIONS: This study suggests that subjects who are occupationally exposed to
      laboratory animals are also exposed to mite derived allergens. Sensitisation to
      mites is common and may be work related.

PMID- 16109818
TI  - Mould/dampness exposure at home is associated with respiratory disorders in
      Italian children and adolescents: the SIDRIA-2 Study.
AB  - AIMS: To report on the relation between home mould and/or dampness exposure and
      respiratory disorders in a large sample of children and adolescents in Italy,
      accounting for age at time of exposure. METHODS: 20,016 children (mean age 7
      years) and 13,266 adolescents (mean age 13 years) completed questionnaires on
      indoor exposures and respiratory symptoms/diseases. Statistical analyses were
      adjusted for sex, age, questionnaire's compiler, area of residence, season of
      interview, parental educational status, family history of asthma, rhinitis,
      eczema, chronic obstructive pulmonary disease, presence of gas water heaters,
      passive smoking, pets, and active smoking (only for adolescents). Population
      attributable risk % (PAR) was also computed. RESULTS: Asthma was more strongly
      related to only early than to only current exposure, both in children (OR 1.80,
      95% CI 1.41 to 2.30) and adolescents (OR 1.89, 95% CI 1.38 to 2.59). The same
      result was found for rhino-conjunctivitis (OR 1.46, 95% CI 1.17 to 1.82), in
      children, and for wheeze among adolescents (OR 1.56, 95% CI 1.15 to 2.11). In
      children, wheeze (OR 1.98, 95% CI 1.47 to 2.66) and eczema (OR 1.44, 95% CI 1.09
      to 1.91) were more strongly related to mould/dampness when exposed both early and
      currently; the same occurred in adolescents for rhino-conjunctivitis (1.78, 95%
      CI 1.30 to 2.45). Although persistent cough/phlegm was significantly related to
      mould/dampness exposure in children, regardless of exposure timing, no
      significant association between mould/dampness exposure and eczema or
      cough/phlegm was found among adolescents. PAR estimates were higher for only
      early than only current exposures. Avoiding early only exposure would abate
      wheeze by 6%, asthma or cough/phlegm by 7%, rhino-conjunctivitis in children by
      4%, and in adolescents, asthma by 6%, and wheeze by 4%. CONCLUSIONS: Respiratory
      disorders such as wheeze and asthma can often be explained by exposure to home
      mould/dampness, especially early in life. The association seems more evident in
      children than in adolescents. These findings may suggest the need for
      environmental prevention strategies.

PMID- 16109819
TI  - Accuracy of a semiquantitative method for Dermal Exposure Assessment (DREAM).
AB  - BACKGROUND: The authors recently developed a Dermal Exposure Assessment Method
      (DREAM), an observational semiquantitative method to assess dermal exposures by
      systematically evaluating exposure determinants using pre-assigned default
      values. AIM: To explore the accuracy of the DREAM method by comparing its
      estimates with quantitative dermal exposure measurements in several occupational
      settings. METHODS: Occupational hygienists observed workers performing a certain
      task, whose exposure to chemical agents on skin or clothing was measured
      quantitatively simultaneously, and filled in the DREAM questionnaire. DREAM
      estimates were compared with measurement data by estimating Spearman correlation
      coefficients for each task and for individual observations. In addition, mixed
      linear regression models were used to study the effect of DREAM estimates on the
      variability in measured exposures between tasks, between workers, and from day to
      day. RESULTS: For skin exposures, spearman correlation coefficients for
      individual observations ranged from 0.19 to 0.82. DREAM estimates for exposure
      levels on hands and forearms showed a fixed effect between and within surveys,
      explaining mainly between-task variance. In general, exposure levels on clothing
      layer were only predicted in a meaningful way by detailed DREAM estimates, which
      comprised detailed information on the concentration of the agent in the
      formulation to which exposure occurred. CONCLUSIONS: The authors expect that the
      DREAM method can be successfully applied for semiquantitative dermal exposure
      assessment in epidemiological and occupational hygiene surveys of groups of
      workers with considerable contrast in dermal exposure levels (variability between
      groups >1.0). For surveys with less contrasting exposure levels, quantitative
      dermal exposure measurements are preferable.

PMID- 16109820
TI  - An assessment of dermal exposure to semi-synthetic metal working fluids by
      different methods to group workers for an epidemiological study on dermatitis.
AB  - BACKGROUND: Assessment of exposure assessment to metal working fluids (MWF) has
      almost exclusively focused on inhalation exposure. AIMS: To assess levels of, and
      factors affecting, dermal and inhalation exposure to semi-synthetic MWF, and to
      identify suitable dermal exposure grouping schemes among metal workers for an
      epidemiological survey on dermatitis of hands, forearms, and head. METHODS: A
      cross-sectional survey was conducted in four metal working machining departments
      of a truck manufacturing plant, estimating dermal and inhalation exposure levels
      to semi-synthetic metal working fluids (SMWF) in machine operators. Dermal
      exposure levels to SMWF were estimated by three different methods for dermal
      exposure assessment (VITAE, surrogate skin pad method, and a semi-quantitative
      dermal exposure assessment method (DREAM)). RESULTS: The identified factors
      affecting dermal exposure were similar for the three methods, although
      differences were found for estimated variability in dermal exposure levels
      between groups, within groups (among workers), and from day to day. With the
      VITAE method differences in exposure levels were detected between workers that
      were not detected with the surrogate skin pad method, and only partly with the
      DREAM method. CONCLUSIONS: Considering the additional effort and costs that use
      of the VITAE method entailed, the observational semi-quantitative DREAM method
      appeared to be more efficient for grouping of dermal exposure levels for the
      epidemiological study on dermatitis.

PMID- 16109821
TI  - A randomised controlled intervention study on prevention of work related skin
      problems among gut cleaners in swine slaughterhouses.
AB  - AIMS: To evaluate the effect of an intervention to reduce work related skin
      problems in gut cleaning departments in Danish swine slaughterhouses. The
      intervention consisted of an evidence based prevention programme and a documented
      method for implementation. METHODS: Randomised controlled intervention study with
      a one year follow up. The intervention included educational activities and
      evidence based recommendations. The effect of the intervention was evaluated by
      telephone interviews using a standardised questionnaire based on the Nordic
      Occupational Skin Questionnaire (NOSQ-2002) with modified and additional
      questions on exposure, preventive measures, information, and discussions on
      prevention of skin problems, etc. RESULTS: A total of 644 (87.5%) responded at
      the baseline interview and 622 (71.6%) at the one year follow up interview. A
      total of 495 participated in both interviews (67.3%). In the intervention
      departments the frequency of eczema on hands or forearms within the past three
      months at follow up was reduced significantly from 56.2% at baseline to 41.0% at
      follow up, while a slight non-significant increase was observed in the comparison
      departments (from 45.9% to 50.2%). The intervention activities resulted in more
      frequent use of protective gloves in general and the use of cotton gloves worn
      underneath rubber and plastic gloves. At follow up three times as many in the
      intervention departments used the recommended high fat skin care products
      introduced as part of the intervention activities. At follow up, discussion of
      skin problems was increased in the intervention group while no changes were
      observed in the comparison group. CONCLUSIONS: A significant 27% relative
      reduction of occupational eczema in a high risk group was feasible through
      implementation of an evidence based prevention programme.

PMID- 16109822
TI  - Respiratory disease and cardiovascular morbidity.
AB  - BACKGROUND: Work related dust exposure is a risk factor for acute and chronic
      respiratory irritation and inflammation. Exposure to dust and cigarette smoke
      predisposes to exogenous viral and bacterial infections of the respiratory tract.
      Respiratory infection can also act as a risk factor in the development of
      atherosclerotic and coronary artery disease. AIMS: To investigate the association
      of dust exposure and respiratory diseases with ischaemic heart disease (IHD) and
      other cardiovascular diseases (CVDs). METHODS: The study comprised 6022 dust
      exposed (granite, foundry, cotton mill, iron foundry, metal product, and
      electrical) workers hired in 1940-76 and followed until the end of 1992. National
      mortality and morbidity registers and questionnaires were used. The statistical
      methods were person-year analysis and Cox regression. RESULTS: Co-morbidity from
      cardiovascular and respiratory diseases ranged from 17% to 35%. In at least 60%
      of the co-morbidity cases a respiratory disease preceded a cardiovascular
      disease. Chronic bronchitis, pneumonia, and upper respiratory track infections
      predicted IHD in granite workers (rate ratio (RR) = 1.9; 95% CI 1.38 to 2.72),
      foundry workers (2.1; 1.48 to 2.93), and iron foundry workers (1.7; 1.16 to
      2.35). Dust exposure was not a significant predictor of IHD or other CVD in any
      group. Dust exposure was related to respiratory morbidity. Thus, some respiratory
      diseases appeared to act as intermediate variables in the association of dust
      exposure with IHD. CONCLUSION: Dust exposure had only a small direct effect on
      IHD and other CVD. IHD morbidity was associated with preceding respiratory
      morbidity. A chronic infectious respiratory tract disease appeared to play an
      independent role in the development of IHD.

PMID- 16109823
TI  - Monitoring of fluoro-edenite fibre pollution through the study of sheep lymph
      nodes as a model of a biological indicator.

PMID- 16109824
TI  - Genetic screening and occupational and environmental exposures.

PMID- 16109825
TI  - The decrease in level of serum thyroxine by 2,2',4,5,5'-pentachlorobiphenyl in
      rats and mice: no correlation with formation of methylsulfonyl metabolites.
AB  - A relationship between formation of methylsulfonyl (MeSO2) metabolites of
      2,2',4,5,5'-pentachlorobiphenyl (PentaCB) and decrease in serum thyroxine (T4)
      level was examined in the rats and mice after a single i.p. injection of PentaCB
      (342 micromol/kg body weight). In either rats or mice, levels of the 3- and 4
      MeSO2 metabolites of PentaCB in the liver and feces increased in a time-dependent
      fashion up to 8 days after PentaCB-treatment. However, there was a marked
      difference between rats and mice in the amount of the metabolites formed, and the
      cumulative amount of the either MeSO2 metabolite for 8 days after PentaCB
      treatment in the liver was 4 to 15 times higher in mice than in rats. On the
      other hand, a 40 to 60% decrease in level of serum total T4 occurred in both rats
      and mice at 1 day after PentaCB treatment, and the decrease was retained up to 8
      days after PentaCB treatment. Thus, there was a marked difference between rats
      and mice in the formation of MeSO2 metabolites from PentaCB but not a significant
      difference between rats and mice in PentaCB-induced decrease in the level of
      serum total T4, indicating that PentaCB-induced decrease in the level of serum
      total T4 is not necessarily dependent on the MeSO2 metabolites formed.

PMID- 16109826
TI  - Effects of chronic hypoxia on MK-801-induced changes in the acute hypoxic
      ventilatory response.
AB  - Chronic hypoxia increases the sensitivity of the central nervous system to
      afferent input from carotid body chemoreceptors. We hypothesized that this
      process involves N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms and
      predicted that chronic hypoxia would change the effect of the NMDA receptor
      blocker dizocilpine (MK-801) on the poikilocapnic hypoxic ventilatory response
      (HVR). Male Sprague-Dawley rats were studied before and after acclimatization to
      hypoxia (70 Torr inspiratory Po(2) for 9 days). We measured ventilation (VI) and
      the HVR before and after systemic MK-801 treatment (3 mg/kg ip). MK-801 resulted
      in a constant respiratory frequency (approximately 175 min(-1)) during acute
      exposure to 10% and 30% O(2) before and after acclimatization. MK-801 had no
      effect on tidal volume (VT) before acclimatization, but it significantly
      decreased Vt when the animals were breathing 10% O(2) after acclimatization. The
      net effect of MK-801 was to eliminate the O(2) sensitivity of Vi before (via
      changes in respiratory frequency) and after (via changes in VT) acclimatization.
      Hence, chronic hypoxia altered the effect of MK-801 on the acute HVR, primarily
      because of increased effects on Vt. This indicates that changes in NMDA receptor
      mediated neurotransmission may be involved in ventilatory acclimatization to
      hypoxia. However, further experiments are necessary to determine the precise
      location of such plasticity in the central nervous system.

PMID- 16109827
TI  - Age and regional specificity of peak limb vascular conductance in women.
AB  - The influence of age on limb vasodilator capacity in women is unclear. The
      objectives of this study were to characterize and compare age-associated changes
      in forearm and calf peak vascular conductance (VC(peak); a functional index of
      arterial structure) in women and to identify physiological characteristics
      predictive of variation in limb-specific VC(peak). Peak conductance
      (plethysmographic flow/mean arterial pressure), VC(peak) of the forearm (forearm
      VC(peak)), and calf (calf VC(peak)) after 10 min of arterial occlusion were
      measured in 58 healthy, normally active women aged 21-79 yr. Aerobic capacity
      (cycle peak oxygen uptake), arterial health (pulse-wave velocity, ankle-brachial
      index), total cholesterol, limb-specific tissue composition (dual-energy X-ray
      absorptiometry), and isometric strength (handgrip, plantar flexion) were also
      assessed. The relative decline in calf VC(peak) with age (-6.8% per decade, P <
      0.001) was greater than the forearm (-4.4% per decade, P = 0.004), in contrast to
      results previously reported for men (forearm decline > calf decline). Limb
      VC(peak) per kilogram muscle declined with age in the calf (-6.0% per decade; P =
      0.002), but not the forearm (P = 0.12). Age, cholesterol, and regional tissue
      composition were significant predictors of peak conductance in both limbs;
      however, age was a stronger predictor of peak conductance in the calf. These
      results suggest that healthy aging is associated with a linear decline in limb
      vasodilator capacity in women, but the magnitude of this effect is region
      specific. Further research will be required to determine whether the decline in
      lower extremity vasodilator capacity with age explains diminished exercising leg
      vasodilation in older women.

PMID- 16109828
TI  - Cardiac overexpression of catalase antagonizes ADH-associated contractile
      depression and stress signaling after acute ethanol exposure in murine myocytes.
AB  - Alcohol dehydrogenase (ADH), which oxidizes ethanol into acetaldehyde,
      exacerbates ethanol-induced cardiac depression, although the mechanism of action
      remains unclear. This study was designed to examine the impact of antioxidant
      catalase (CAT) on cardiac contractile response to ethanol and activation of
      stress signaling. ADH-CAT double transgenic mice were generated by crossing CAT
      and ADH lines. Mechanical, intracellular Ca(2+) properties and reactive oxygen
      species generation were measured in ventricular myocytes. ADH-CAT, ADH, CAT and
      wild-type FVB myocytes exhibited similar mechanical and intracellular Ca(2+)
      properties. ADH or ADH-CAT myocytes had higher acetaldehyde-producing ability.
      Ethanol (80-640 mg/dl) suppressed FVB cell shortening and intracellular Ca(2+)
      transients with maximal inhibitions of 43.5 and 45.2%, respectively. Ethanol
      induced depression on cell shortening and intracellular Ca(2+) was augmented in
      ADH group with maximal inhibitions of 66.8 and 69.6%, respectively.
      Interestingly, myocytes from CAT-ADH mice displayed normal ethanol response with
      maximal inhibitions of 46.0 and 47.2% for cell shortening and intracellular
      Ca(2+), respectively. CAT transgene lessened ethanol-induced inhibition on cell
      shortening (maximal inhibition of 30.3%) but not intracellular Ca(2+). ADH
      amplified ethanol-induced reactive oxygen species generation, which was nullified
      by the CAT transgene. Western blot analysis showed that ethanol reduced ERK
      phosphorylation and enhanced JNK phosphorylation without affecting p38
      phosphorylation. The ethanol-induced changes in phosphorylation of ERK and JNK
      were amplified by ADH. CAT transgene itself did not affect ethanol-induced
      response in ERK and JNK phosphorylation, but it cancelled ADH-induced effects.
      These data suggest that antioxidant CAT may effectively antagonize ADH-induced
      enhanced cardiac depression in response to ethanol.

PMID- 16109829
TI  - Role of acid-base balance in the chemoreflex control of breathing.
AB  - This paper uses a steady-state modeling approach to describe the effects of
      changes in acid-base balance on the chemoreflex control of breathing. First, a
      mathematical model is presented, which describes the control of breathing by the
      respiratory chemoreflexes; equations express the dependence of pulmonary
      ventilation on Pco(2) and Po(2) at the central and peripheral chemoreceptors.
      These equations, with Pco(2) values as inputs to the chemoreceptors, are
      transformed to equations with hydrogen ion concentrations [H(+)] in brain
      interstitial fluid and arterial blood as inputs, using the Stewart approach to
      acid-base balance. Examples illustrate the use of the model to explain the
      regulation of breathing during acid-base disturbances. They include diet-induced
      changes in sodium and chloride, altitude acclimatization, and respiratory
      disturbances of acid-base balance due to chronic hyperventilation and carbon
      dioxide retention. The examples demonstrate that the relationship between Pco(2)
      and [H(+)] should not be neglected when modeling the chemoreflex control of
      breathing. Because pulmonary ventilation controls Pco(2) rather than the actual
      stimulus to the chemoreceptors, [H(+)], changes in their relationship will alter
      the ventilatory recruitment threshold Pco(2), and thereby the steady-state
      resting ventilation and Pco(2).

PMID- 16109830
TI  - Mechanisms underlying increases in rat soleus Na+-K+-ATPase activity by induced
      contractions.
AB  - Acute regulation of the Na(+)-K(+)-ATPase activity in rat soleus muscle was
      investigated in response to 15 and 90 min of electrically induced contractile
      activity (500-ms trains at 30 Hz every 1.5 s). Kinetic measurements of Na(+)-K(+)
      ATPase activity, assessed by the 3-O-methylfluorescein K(+)-stimulated
      phosphatase assay (3-O-MFP), were performed on crude homogenates (Hom) and on
      tissue separated into two membrane fractions, the sarcolemmal/particulate (SLP)
      and endosomal (En), in both stimulated (Stim) and contralateral control (Con)
      muscles. Maximal 3-O-MFP activity (V(max), nmol.mg protein(-1).h(-1)) was
      elevated (P < 0.05) in Stim by 40% and by 53% in Hom and by 37 and 40% in SLP at
      15 and 90 min, respectively. The 38% increase (P < 0.05) in the alpha(2)-isoform
      subunit distribution in SLP at 15 min, as assessed by quantitative
      immunoblotting, persisted at 90 min, whereas for En a 42% decrease (P < 0.05) was
      observed only at 15 min. For the alpha(1)-subunit at 15 min, a 27% decrease (P <
      0.05) was observed in En, whereas the 13% increase observed in SLP was not
      significant (P = 0.08). At 90 min, alpha(1) was increased (P < 0.05) by 14% in
      SLP and by 29% in En. No changes were observed in beta(1)-subunit distribution in
      En and SLP regardless of time of stimulation. Immunoprecipitation with
      antiphosphotyrosine antibody and quantitative immunoblotting with alpha(1)- and
      alpha(2)-antibodies indicated increases (P < 0.05) in tyrosine phosphorylation of
      51% in alpha(2) at 15 min only. These results suggest that the increases in
      V(max) during contractile activity are mediated both by increased phosphorylation
      and by translocation of the enzyme to the plasma membrane.

PMID- 16109831
TI  - Separation of bronchoconstriction from increased ventilatory drive in a nonhuman
      primate model of chronic allergic asthma.
AB  - The relationship between allergen-induced ventilatory drive and
      bronchoconstriction was investigated in dust mite-sensitive cynomolgus macaques
      periodically exposed to low doses of aerosolized antigen for up to 5.5 yr.
      Initially, the animals responded to aerosolized dust mite allergen at a
      concentration of 350 arbitrary units (AU)/ml with simultaneous increases in lung
      resistance (RL) and respiratory rate (RR). With time, RL and RR became
      differentially sensitive to allergen provocation. At the end of the study period,
      aerosolized allergen at a concentration of 15 AU/ml doubled RR without increasing
      RL. When mechanically ventilated to maintain tidal volume, higher concentrations
      of allergen could be delivered, and RL increased. Inhaled disodium cromoglycate
      and intravenous diphenhydramine attenuated the increase in RR, indicating that
      allergen-induced release of histamine and activation of H(1) receptors mediated
      the response. Inhaled beta-adrenergic agonists attenuated the RR response to dust
      mite and to direct histamine provocation. These results demonstrate that chronic
      periodic allergen challenge increases the allergic sensitivity of histamine
      dependent reflexes controlling ventilatory drive. Activation of these reflexes is
      independent of overt bronchoconstriction, but can be inhibited by beta-adrenergic
      agonists, indicating that beta-adrenergic agonists exert their effect independent
      of bronchodilation.

PMID- 16109832
TI  - Vasoactive intestinal peptide fragment VIP10-28 and active vasodilation in human
      skin.
AB  - A recent study reported the vasoactive intestinal peptide (VIP) fragment VIP(10
      28) inhibited the rise in skin blood flow during heat stress. Our laboratory has
      reported that the nitric oxide (NO) pathway and histamine receptor-1 (H1)
      receptor activation is common to both exogenous VIP-mediated dilation and active
      vasodilation (AVD). The present study aimed to further examine the specific role
      for VIP in AVD by using VIP(10-28) to antagonize VIP-mediated dilation in the
      presence of NO synthase (NOS) inhibition and an H1 antagonist. Study 1 (n = 12)
      examined whether VIP(10-28) antagonizes vasodilation to exogenous VIP via
      inhibition of NO-dependent mechanisms. Study 2 (n = 6) investigated AVD in skin
      sites receiving VIP(10-28) alone and in combination with NOS inhibition. Study 3
      (n = 6) examined AVD in sites receiving VIP(10-28) alone and combined VIP(10-28)
      and H1 antagonism. Due to differences in our findings and those previously
      published, study 4 (n = 6) investigated whether an increase in baseline skin
      blood flow could result in a diminished rise in AVD. Red blood cell flux was
      measured using laser Doppler flowmetry, and cutaneous vascular conductance
      (flux/mean arterial pressure) was normalized to maximal vasodilation (28 mM
      sodium nitroprusside). VIP(10-28) augmented vasodilation to exogenous VIP (P <
      0.05 vs. control) and hyperthermia (P < 0.05 vs. control). NOS inhibition had no
      effect on the augmented dilation during exogenous VIP or hyperthermia (P > 0.05).
      Similarly, H1-receptor antagonists had no effect on the augmented dilation during
      hyperthermia (P > 0.05 vs. VIP(10-28)). In study 4, percentage of maximal
      cutaneous vascular conductance was attenuated when baseline skin blood flow was
      elevated before whole body heating. Our results suggest that VIP(10-28) may be an
      unsuitable antagonist for examining a role for VIP-mediated dilation in human
      skin.

PMID- 16109833
TI  - In vitro time-dependent response of periodontal ligament to mechanical loading.
AB  - This study examined the time-dependent response of bovine periodontal ligament
      (PDL). Applying linear viscoelastic theory, the objective was 1) to examine the
      linearity of the PDL's response in terms of its scaling and superposition
      property and 2) to generate the phase lag-vs.-frequency spectrum graph. PDL
      specimens were tested under three separate straining conditions: 1) tension ramp
      tests conducted at different strain rates, 2) pulling step-straining to 0.3 in
      discrete tests and to 0.3 and 0.6 in one continuous run, and 3) tension
      compression sinusoidal oscillations. To this effect, bar-shaped specimens of
      bovine roots that comprised portions of dentin, PDL tissue, and alveolar bone
      were produced and strained in a microtensile machine. The experimental data
      demonstrated that neither the scaling nor the superposition properties were
      verified and that the viscoelastic response of the PDL was nonlinear. The PDL's
      elastic response was essentially stiffening, and its viscous component was
      pseudoplastic. The tangent of the PDL's strain-stress phase lag was in the 0-0.1
      range in the tensile direction and in the 0.35-0.45 range in the compressive
      direction. In line with other biological tissues, the phase lag was largely
      independent of frequency. By use of the data generated, a mathematical model is
      outlined that reproduces both the elastic stiffening and viscous thinning of the
      PDL's response.

PMID- 16109834
TI  - Time course of lung parenchyma remodeling in pulmonary and extrapulmonary acute
      lung injury.
AB  - The aim of this study is to test the hypothesis that the early changes in lung
      mechanics and the amount of type III collagen fiber do not predict the evolution
      of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury
      (ALI). For this purpose, we analyzed the time course of lung parenchyma
      remodeling in murine models of pulmonary and extrapulmonary ALI with similar
      degrees of mechanical compromise at the early phase of ALI. Lung histology (light
      and electron microscopy), the amount of elastic and collagen fibers in the
      alveolar septa, the expression of matrix metalloproteinase-9, and mechanical
      parameters (lung-resistive and viscoelastic pressures, and static elastance) were
      analyzed 24 h, 1, 3, and 8 wk after the induction of lung injury. In control (C)
      pulmonary (p) and extrapulmonary (exp) groups, saline was intratracheally (it;
      0.05 ml) instilled and intraperitoneally (ip; 0.5 ml) injected, respectively. In
      ALIp and ALIexp groups, mice received Escherichia coli lipopolysaccharide (10
      microg it and 125 microg ip, respectively). At 24 h, all mechanical and
      morphometrical parameters, as well as type III collagen fiber content, increased
      similarly in ALIp and ALIexp groups. In ALIexp, all mechanical and histological
      data returned to control values at 1 wk. However, in ALIp, static elastance
      returned to control values at 3 wk, whereas resistive and viscoelastic pressures,
      as well as type III collagen fibers and elastin, remained elevated until week 8.
      ALIp showed higher expression of matrix metalloproteinase-9 than ALIexp. In
      conclusion, insult in pulmonary epithelium yielded fibroelastogenesis, whereas
      mice with ALI induced by endothelial lesion developed only fibrosis that was
      repaired early in the course of lung injury. Furthermore, early functional and
      morphological changes did not predict lung parenchyma remodeling.

PMID- 16109835
TI  - Effect of gestational stage on uterine artery blood flow during exercise in
      rabbits.
AB  - We tested the hypothesis that the uterine artery vasoconstrictor response to
      graded exercise during early gestation would be similar to the nonpregnant (NP)
      state and would be attenuated at mid and term gestation. Responses to graded
      treadmill exercise were measured in six female New Zealand White rabbits in the
      NP state and at day 10, day 20, and day 28 (term) of gestation. Uterine artery
      blood flow (UtBF) was measured continuously with a Transonic flow probe. Rabbits
      performed a graded exercise test to voluntary exhaustion (maximal exercise)
      starting at 7 m/min, 7% grade. UtBF and uterine artery conductance (UtC)
      decreased similarly during graded exercise (P < 0.01) in the NP state [at maximal
      exercise: -40% (SD 20) for UtBF and -45% (SD 14) for UtC] and at day 10 of
      gestation [at maximal exercise: -48% (SD 17) for UtBF; -56% (SD 14) for UtC]. In
      contrast, there was little change in UtBF or UtC during graded exercise at day 20
      [at maximal exercise: -4% (SD 17) for UtBF, P < 0.05 vs. NP; -16% (SD 12) for
      UtC, P < 0.01 vs. NP] and at day 28 [At maximal exercise: +7% (SD 15) for UtBF, P
      < 0.01 vs. NP; -2% (SD 24) for UtC, P < 0.01 vs. NP], indicating substantial
      attenuation of the uterine artery vasoconstrictor response to exercise. At rest,
      UtC responses to graded doses of intravenous phenylephrine were unaffected by the
      stage of gestation, which suggests that uterine artery responsiveness to alpha(1)
      adrenoreceptor stimulation is preserved through gestation. Normal pregnancy in
      the rabbit is associated with attenuation of the uterine artery vasoconstrictor
      response to graded exercise that develops by mid gestation.

PMID- 16109836
TI  - Heterodimerization of g protein-coupled receptors: specificity and functional
      significance.
AB  - G protein-coupled receptors (GPCRs) are cell surface receptors that mediate
      physiological responses to a diverse array of stimuli. GPCRs have traditionally
      been thought to act as monomers, but recent evidence suggests that GPCRs may form
      dimers (or higher-order oligomers) as part of their normal trafficking and
      function. In fact, certain GPCRs seem to have a strict requirement for
      heterodimerization to attain proper surface expression and functional activity.
      Even those GPCRs that do not absolutely require heterodimerization may still
      specifically associate with other GPCR subtypes, sometimes resulting in dramatic
      effects on receptor pharmacology, signaling, and/or internalization.
      Understanding the specificity and functional significance of GPCR
      heterodimerization is of tremendous clinical importance since GPCRs are the
      molecular targets for numerous therapeutic drugs.

PMID- 16109837
TI  - Stem cell approaches for the treatment of renal failure.
AB  - The inadequacy of current treatment modalities and insufficiency of donor organs
      for cadaveric transplantation have driven a search for improved methods of
      dealing with renal failure. The rising concept of cell-based therapeutics has
      provided a framework around which new approaches are being generated, and its
      combination with advances in stem cell research stands to bring both fields to
      clinical fruition. This budding partnership is presently in its very early
      stages, but an examination of the cell-based therapies currently under
      development clearly shows the magnitude of the role that stem cells will
      ultimately play. The issue over reports of unexpected plasticity in adult stem
      cell differentiation remains a focus of debate, and evidence for bone marrow
      derived stem cell contributions to renal repair has been challenged. The search
      for adult renal stem cells, which could have a considerable impact on much of the
      work discussed here, appears to be narrowing. The use of embryonic tissue in
      research continues to provide valuable insights but will be the subject of
      intense societal scrutiny and debate before it reaches the stage of clinical
      application. Embryonic stem (ES) cells, with their ability to generate all, or
      nearly all, of the cell types in the adult body and a possible source of cells
      genetically identical to the donor, hold great promise but face ethical and
      political hurdles for human use. Immunoisolation of heterologous cells by
      encapsulation creates opportunities for their safe use as a component of
      implanted or ex vivo devices.

PMID- 16109838
TI  - Gastrointestinal function regulation by nitrergic efferent nerves.
AB  - Gastrointestinal (GI) smooth muscle responses to stimulation of the nonadrenergic
      noncholinergic inhibitory nerves have been suggested to be mediated by
      polypeptides, ATP, or another unidentified neurotransmitter. The discovery of
      nitric-oxide (NO) synthase inhibitors greatly contributed to our understanding of
      mechanisms involved in these responses, leading to the novel hypothesis that NO,
      an inorganic, gaseous molecule, acts as an inhibitory neurotransmitter. The
      nerves whose transmitter function depends on the NO release are called
      "nitrergic", and such nerves are recognized to play major roles in the control of
      smooth muscle tone and motility and of fluid secretion in the GI tract.
      Endothelium-derived relaxing factor, discovered by Furchgott and Zawadzki, has
      been identified to be NO that is biosynthesized from l-arginine by the
      constitutive NO synthase in endothelial cells and neurons. NO as a mediator or
      transmitter activates soluble guanylyl cyclase and produces cyclic GMP in smooth
      muscle cells, resulting in relaxation of the vasculature. On the other hand, NO
      induced GI smooth muscle relaxation is mediated, not only by cyclic GMP directly
      or indirectly via hyperpolarization, but also by cyclic GMP-independent
      mechanisms. Numerous cotransmitters and cross talk of autonomic efferent nerves
      make the neural control of GI functions complicated. However, the findingsrelated
      to the nitrergic innervation may provide us a new way of understanding GI tract
      physiology and pathophysiology and might result in the development of new
      therapies of GI diseases. This review article covers the discovery of nitrergic
      nerves, their functional roles, and pathological implications in the GI tract.

PMID- 16109839
TI  - Insights into seven and single transmembrane-spanning domain receptors and their
      signaling pathways in human natural killer cells.
AB  - Human natural killer (NK) cells are important cells of the innate immune system.
      These cells perform two prominent functions: the first is recognizing and
      destroying virally infected cells and transformed cells; the second is secreting
      various cytokines that shape up the innate and adaptive immune re-sponses. For
      these cells to perform these activities, they express different sets of
      receptors. The receptors used by NK cells to extravasate into sites of injury
      belong to the seven transmembrane (7TM) family of receptors, which
      characteristically bind heterotrimeric G proteins. These receptors allow NK cells
      to sense the chemotactic gradients and activate second messengers, which aid NK
      cells in polarizing and migrating toward the sites of injured tissues. In
      addition, these receptors determine how and why human resting NK cells are mainly
      found in the bloodstream, whereas activated NK cells extravasate into
      inflammatory sites. Receptors for chemokines and lysophospholipids belong to the
      7TM family. On the other hand, NK cells recognize invading or transformed cells
      through another set of receptors that belong to the single transmembrane-spanning
      domain family. These receptors are either inhibitory or activating. Inhibitory
      receptors contain the immune receptor tyrosine-based inhibitory motif, and
      activating receptors belong to either those that associate with adaptor molecules
      containing the immune receptor tyrosine-based activating motif (ITAM) or those
      that associate with adaptor molecules containing motifs other than ITAM. This
      article will describe the nature of these receptors and examine the intracellular
      signaling pathways induced in NK cells after ligating both types of receptors.
      These pathways are crucial for NK cell biology, development, and functions.

PMID- 16109840
TI  - Regulation of aromatase expression in estrogen-responsive breast and uterine
      disease: from bench to treatment.
AB  - A single gene encodes the key enzyme for estrogen biosynthesis termed aromatase,
      inhibition of which effectively eliminates estrogen production. Aromatase
      inhibitors successfully treat breast cancer and endometriosis, whereas their
      roles in endometrial cancer, uterine fibroids, and aromatase excess syndrome are
      less clear. Ovary, testis, adipose tissue, skin, hypothalamus, and placenta
      express aromatase normally, whereas breast and endometrial cancers,
      endometriosis, and uterine fibroids overexpress aromatase and produce local
      estrogen that exerts paracrine and intracrine effects. Tissue-specific promoters
      distributed over a 93-kilobase regulatory region upstream of a common coding
      region alternatively control aromatase expression. A distinct set of
      transcription factors regulates each promoter in a signaling pathway- and tissue
      specific manner. Three mechanisms are responsible for aromatase overexpression in
      a pathologic tissue versus its normal counterpart. First, cellular composition is
      altered to increase aromatase-expressing cell types that use distinct promoters
      (breast cancer). Second, molecular alterations in stromal cells favor binding of
      transcriptional enhancers versus inhibitors to a normally quiescent aromatase
      promoter and initiate transcription (breast/endometrial cancer, endometriosis,
      and uterine fibroids). Third, heterozygous mutations, which cause the aromatase
      coding region to lie adjacent to constitutively active cryptic promoters that
      normally transcribe other genes, result in excessive estrogen formation owing to
      the overexpression of aromatase in many tissues.

PMID- 16109841
TI  - The calcium-sensing receptor acts as a modulator of gastric acid secretion in
      freshly isolated human gastric glands.
AB  - Gastric acid secretion is activated by two distinct pathways: a neuronal pathway
      via the vagus nerve and release of acetylcholine and an endocrine pathway
      involving gastrin and histamine. Recently, we demonstrated that activation of
      H(+)-K(+)-ATPase activity in parietal cells in freshly isolated rat gastric
      glands is modulated by the calcium-sensing receptor (CaSR). Here, we investigated
      if the CaSR is functionally expressed in freshly isolated gastric glands from
      human patients undergoing surgery and if the CaSR is influencing histamine
      induced activation of H(+)-K(+)-ATPase activity. In tissue samples obtained from
      patients, immunohistochemistry demonstrated the expression in parietal cells of
      both subunits of gastric H(+)-K(+)-ATPase and the CaSR. Functional experiments
      using the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and 6)
      carboxyfluorescein and measurement of intracellular pH changes allowed us to
      estimate the activity of H(+)-K(+)-ATPase in single freshly isolated human
      gastric glands. Under control conditions, H(+)-K(+)-ATPase activity was
      stimulated by histamine (100 microM) and inhibited by omeprazole (100 microM).
      Reduction of the extracellular divalent cation concentration (0 Mg(2+), 100
      microM Ca(2+)) inactivated the CaSR and reduced histamine-induced activation of
      H(+)-K(+)-ATPase activity. In contrast, activation of the CaSR with the trivalent
      cation Gd(3+) caused activation of omeprazole-sensitive H(+)-K(+)-ATPase activity
      even in the absence of histamine and under conditions of low extracellular
      divalent cations. This stimulation was not due to release of histamine from
      neighbouring enterochromaffin-like cells as the stimulation persisted in the
      presence of the H(2) receptor antagonist cimetidine (100 microM). Furthermore,
      intracellular calcium measurements with fura-2 and fluo-4 showed that activation
      of the CaSR by Gd(3+) led to a sustained increase in intracellular Ca(2+) even
      under conditions of low extracellular divalent cations. These experiments
      demonstrate the presence of a functional CaSR in the human stomach and show that
      this receptor may modulate the activity of acid-secreting H(+)-K(+)-ATPase in
      parietal cells. Furthermore, our results show the viability of freshly isolated
      human gastric glands and may allow the use of this preparation for experiments
      investigating the physiological regulation and properties of human gastric glands
      in vitro.

PMID- 16109842
TI  - Changes in guinea pig gallbladder smooth muscle Ca2+ homeostasis by acute
      acalculous cholecystitis.
AB  - Impaired smooth muscle contractility is a hallmark of acute acalculous
      cholecystitis. Although free cytosolic Ca2+ ([Ca2+]i) is a critical step in
      smooth muscle contraction, possible alterations in Ca2+ homeostasis by
      cholecystitis have not been elucidated. Our aim was to elucidate changes in the
      Ca2+ signaling pathways induced by this gallbladder dysfunction. [Ca2+]i was
      determined by epifluorescence microscopy in fura 2-loaded isolated gallbladder
      smooth muscle cells, and isometric tension was recorded from gallbladder muscle
      strips. F-actin content was quantified by confocal microscopy. Ca2+ responses to
      the inositol trisphosphate (InsP3) mobilizing agonist CCK and to caffeine, an
      activator of the ryanodine receptors, were impaired in cholecystitic cells. This
      impairment was not the result of a decrease in the size of the releasable pool.
      Inflammation also inhibited Ca2+ influx through L-type Ca2+ channels and
      capacitative Ca2+ entry induced by depletion of intracellular Ca2+ pools. In
      addition, the pharmacological phenotype of these channels was altered in
      cholecystitic cells. Inflammation impaired contractility further than Ca2+ signal
      attenuation, which could be related to the decrease in F-actin that was detected
      in cholecystitic smooth muscle cells. These findings indicate that cholecystitis
      decreases both Ca2+ release and Ca2+ influx in gallbladder smooth muscle, but a
      loss in the sensitivity of the contractile machinery to Ca2+ may also be
      responsible for the impairment in gallbladder contractility.

PMID- 16109843
TI  - Helicobacter pylori and cholesterol gallstone formation in C57L/J mice: a
      prospective study.
AB  - Recently, we demonstrated that cholesterol gallstone-prone C57L/J mice rarely
      develop gallstones unless they are infected with certain cholelithogenic
      enterohepatic Helicobacter species. Because the common gastric pathogen H. pylori
      has been identified in the hepatobiliary tree of cholesterol gallstone patients,
      we wanted to ascertain if H. pylori is cholelithogenic, by prospectively studying
      C57L infected mice fed a lithogenic diet. Weanling, Helicobacter spp.-free male
      C57L mice were either infected with H. pylori SS1 or sham dosed. Mice were then
      fed a lithogenic diet (1.0% cholesterol, 0.5% cholic acid, and 15% dairy
      triglycerides) for 8 wk. At 16 wk of age, mice were euthanatized, the biliary
      phenotype was analyzed microscopically, and tissues were analyzed
      histopathologically. H. pylori infection did not promote cholesterol monohydrate
      crystal formation (20% vs. 10%), sandy stone formation (0% for both), or true
      gallstone formation (20%) compared with uninfected mice fed the lithogenic diet
      (10%). Additionally, H. pylori failed to stimulate mucin gel accumulation in the
      gallbladder or alter gallbladder size compared with uninfected animals. H. pylori
      infected C57L mice developed moderate to severe gastritis by 12 wk, and the
      lithogenic diet itself produced lesions in the forestomach, which were
      exacerbated by the infection. We conclude that H. pylori infection does not play
      any role in murine cholesterol gallstone formation. Nonetheless, the C57L mouse
      develops severe lesions of both the glandular and nonglandular stomach in
      response to H. pylori infection and the lithogenic diet, respectively.

PMID- 16109844
TI  - Characterization of the Na+-dependent Mg2+ transport in sheep ruminal epithelial
      cells.
AB  - This study examines the routes by which Mg2+ leaves cultured ovine ruminal
      epithelial cells (REC). Mg2+-loaded (6 mM) REC were incubated in completely Mg2+
      free solutions with varying Na+ concentrations, and the Mg2+ extrusion rate was
      calculated from the increase of the Mg2+ concentration in the incubation medium
      determined with the aid of the fluorescent probe mag-fura 2 (Na+ salt). In other
      experiments, REC were also studied for the intracellular free Mg2+ concentration
      ([Mg2+]i; using mag-fura 2), the intracellular Na+ concentration (using Na+
      binding benzofuran isophthalate), the intracellular cAMP concentration ([cAMP]i;
      using an enzyme-linked immunoassay), and Na+/Mg2+ exchanger existence [using a
      monoclonal antibody (mAb) raised against the porcine red blood cell Na+/Mg2+
      exchanger]. Mg2+-loaded REC show a Mg2+ efflux that was strictly dependent on
      extracellular Na+. The Mg2+ extrusion rate increased from 0.018+/-0.009 in a Na+
      free medium to 0.73+/-0.3 mM.l cells-1.min-1 in a 145 mM Na+ medium and relates
      to extracellular Na+ concentration ([Na+]e) according to a typical saturation
      kinetic (Km value for [Na+]e=24 mM; maximal velocity=11 mM.l cells-1.min-1). Mg2+
      efflux was reduced by imipramine (48%) and increased after application of
      dibutyryl-cAMP (55%) or PGE2 (17%). These effects are completely abolished in Na+
      free media. Furthermore, an elevation of [cAMP]i led to an [Mg2+]i decrease that
      amounted to 375+/-105 microM. The anti-Na+/Mg2+ exchanger mAb inhibits Mg2+
      extrusion; moreover, it detects a specific 70-kDa immunoreactive band in protein
      lysates of ovine REC. The data clearly demonstrate that a Na+/Mg2+ exchanger is
      existent in the cell membrane of REC. The transport protein is the main pathway
      (97%) for Mg2+ extrusion and can be assumed to play a considerable role in the
      process of Mg2+ absorption as well as the maintenance of the cellular Mg2+
      homeodynamics.

PMID- 16109845
TI  - Bright x-ray flares in gamma-ray burst afterglows.
AB  - Gamma-ray burst (GRB) afterglows have provided important clues to the nature of
      these massive explosive events, providing direct information on the nearby
      environment and indirect information on the central engine that powers the burst.
      We report the discovery of two bright x-ray flares in GRB afterglows, including a
      giant flare comparable in total energy to the burst itself, each peaking minutes
      after the burst. These strong, rapid x-ray flares imply that the central engines
      of the bursts have long periods of activity, with strong internal shocks
      continuing for hundreds of seconds after the gamma-ray emission has ended.

PMID- 16109846
TI  - Extensive diversity of Ig-superfamily proteins in the immune system of insects.
AB  - The extensive somatic diversification of immune receptors is a hallmark of higher
      vertebrates. However, whether molecular diversity contributes to immune
      protection in invertebrates is unknown. We present evidence that Drosophila
      immune-competent cells have the potential to express more than 18,000 isoforms of
      the immunoglobulin (Ig)-superfamily receptor Down syndrome cell adhesion molecule
      (Dscam). Secreted protein isoforms of Dscam were detected in the hemolymph, and
      hemocyte-specific loss of Dscam impaired the efficiency of phagocytic uptake of
      bacteria, possibly due to reduced bacterial binding. Importantly, the molecular
      diversity of Dscam transcripts generated through a mechanism of alternative
      splicing is highly conserved across major insect orders, suggesting an
      unsuspected molecular complexity of the innate immune system of insects.

PMID- 16109847
TI  - Late Cenozoic moisture history of East Africa.
AB  - Lake sediments in 10 Ethiopian, Kenyan, and Tanzanian rift basins suggest that
      there were three humid periods at 2.7 to 2.5 million years ago (Ma), 1.9 to 1.7
      Ma, and 1.1 to 0.9 Ma, superimposed on the longer-term aridification of East
      Africa. These humid periods correlate with increased aridity in northwest and
      northeast Africa and with substantial global climate transitions. These episodes
      could have had important impacts on the speciation and dispersal of mammals and
      hominins, because a number of key events, such as the origin of the genus Homo
      and the evolution of the species Homo erectus, took place in this region during
      that time.

PMID- 16109849
TI  - Anniversary reflections.

PMID- 16109848
TI  - Circadian clock control by SUMOylation of BMAL1.
AB  - The molecular machinery that governs circadian rhythmicity is based on clock
      proteins organized in regulatory feedback loops. Although posttranslational
      modification of clock proteins is likely to finely control their circadian
      functions, only limited information is available to date. Here, we show that
      BMAL1, an essential transcription factor component of the clock mechanism, is
      SUMOylated on a highly conserved lysine residue (Lys259) in vivo. BMAL1 shows a
      circadian pattern of SUMOylation that parallels its activation in the mouse
      liver. SUMOylation of BMAL1 requires and is induced by CLOCK, the
      heterodimerization partner of BMAL1. Ectopic expression of a SUMO-deficient BMAL1
      demonstrates that SUMOylation plays an important role in BMAL1 circadian
      expression and clock rhythmicity. This reveals an additional level of regulation
      within the core mechanism of the circadian clock.

PMID- 16109850
TI  - Wildlife biology. 'Genetic rescue' helps panthers but puts researchers on the
      spot.

PMID- 16109851
TI  - Evolution. Kansas prepares new standards.

PMID- 16109853
TI  - U.S. polar science. NSF taps Russian vessel for Antarctic icebreaking.

PMID- 16109852
TI  - High-energy physics. Costs force NSF to cancel Brookhaven Project.

PMID- 16109854
TI  - Space and earth sciences. Budget woes greet NASA science chief.

PMID- 16109855
TI  - Immunology. Versatile development gene aids insect immune response.

PMID- 16109857
TI  - Astronomy. Second failure cripples Suzaku satellite.

PMID- 16109856
TI  - Environmental science. Sperm whales bear testimony to worldwide pollution.

PMID- 16109858
TI  - Nuclear power. Is the friendly atom poised for a comeback?

PMID- 16109859
TI  - Map. Nuclear power's expanding territory.

PMID- 16109860
TI  - Reactors. Nuclear industry dares to dream of a new dawn.

PMID- 16109861
TI  - Rethinking nuclear power. India's homegrown thorium reactor.

PMID- 16109862
TI  - Asia's demand for electricity fuels a regional nuclear boom.

PMID- 16109863
TI  - Rethinking nuclear power. Down to earth: lingering nuclear waste.

PMID- 16109864
TI  - The problem of child sexual abuse.

PMID- 16109865
TI  - A celebration of ignorance.

PMID- 16109866
TI  - What are our research priorities?

PMID- 16109867
TI  - Comment on "Quantum state transfer between matter and light".

PMID- 16109868
TI  - Careers in science. More women in science.

PMID- 16109869
TI  - Chemistry. X-ray fingerprinting of chemical intermediates in solution.

PMID- 16109870
TI  - Evolution. Is invariance across animal species just an illusion?

PMID- 16109871
TI  - Chemistry. Geometric phase in chemical reactions.

PMID- 16109872
TI  - Physiology. Biological clocks coordinately keep life on time.

PMID- 16109873
TI  - Physics. Freezing and melting: action at grain boundaries.

PMID- 16109874
TI  - The convergence of synthetic organic and polymer chemistries.
AB  - Several recent conceptual advances, which take advantage of the design criteria
      and practical techniques of molecular-level control in organic chemistry, allow
      preparation of well-defined polymers and nanostructured materials. Two trends are
      clear: the realization that synthesis of complex macromolecules poses major
      challenges and opportunities and the expectation that such materials will exhibit
      distinctive properties and functions. Polymer synthesis methods now being
      developed will yield well-defined synthetic macromolecules that are capable of
      mimicking many of the features of proteins (for example, three-dimensional folded
      structure) and other natural materials. These macromolecules have far-reaching
      potential for the study of molecular-level behavior at interfaces, in thin films,
      and in solution, while also enabling the development of encapsulation, drug
      delivery, and nanoscale-patterning technologies.

PMID- 16109875
TI  - Strong, transparent, multifunctional, carbon nanotube sheets.
AB  - Individual carbon nanotubes are like minute bits of string, and many trillions of
      these invisible strings must be assembled to make useful macroscopic articles. We
      demonstrated such assembly at rates above 7 meters per minute by cooperatively
      rotating carbon nanotubes in vertically oriented nanotube arrays (forests) and
      made 5-centimeter-wide, meter-long transparent sheets. These self-supporting
      nanotube sheets are initially formed as a highly anisotropic electronically
      conducting aerogel that can be densified into strong sheets that are as thin as
      50 nanometers. The measured gravimetric strength of orthogonally oriented sheet
      arrays exceeds that of sheets of high-strength steel. These nanotube sheets have
      been used in laboratory demonstrations for the microwave bonding of plastics and
      for making transparent, highly elastomeric electrodes; planar sources of
      polarized broad-band radiation; conducting appliques; and flexible organic light
      emitting diodes.

PMID- 16109876
TI  - Theoretical study of geometric phase effects in the hydrogen-exchange reaction.
AB  - The crossing of two electronic potential surfaces (a conical intersection) should
      result in geometric phase effects even for molecular processes confined to the
      lower surface. However, recent quantum simulations of the hydrogen exchange
      reaction (H + H2 --> H2 + H) have predicted a cancellation in such effects when
      product distributions are integrated over all scattering angles. We used a simple
      topological argument to extract reaction paths with different senses from a
      nuclear wave function that encircles a conical intersection. In the hydrogen
      exchange reaction, these senses correspond to paths that cross one or two
      transition states. These two sets of paths scatter their products into different
      regions of space, which causes the cancellation in geometric phase effects. The
      analysis should generalize to other direct reactions.

PMID- 16109877
TI  - Colloidal hard-sphere crystal growth frustrated by large spherical impurities.
AB  - Impurities affect the nucleation, growth, and structure of crystals. Here we
      report the effect of large, spherical, polymethylmethacrylate impurities on the
      crystal growth of monodisperse, hard, polymethylmethacrylate colloids in a
      density- and optically matching apolar solvent mixture. Crystal growth, initiated
      at the bottom of the sample, was studied by imaging sequences of two-dimensional
      xy slices in the plane of the impurity's center with a laser scanning confocal
      microscope. Impurities form the center of grain boundaries, and a single fluid
      particle layer around the impurity persists in all cases. The growth rate
      sensitively depends on the impurity's size. Crystal growth is inhibited to a
      greater extent near smaller impurities, pointing to local crystal frustration
      induced by the curvature of the impurity.

PMID- 16109878
TI  - Osmium isotope evidence for an s-process carrier in primitive chondrites.
AB  - Osmium extracted from unequilibrated bulk chondrites has isotope anomalies
      consistent with an insoluble s-process carrier, termed Os(i) here. Osmium from
      metamorphosed bulk chondrites does not have isotope anomalies, implying that the
      Os(i) carrier was destroyed by metamorphism. The isotopic homogeneity of
      metamorphosed bulk chondrites is consistent with extremely effective mixing of
      presolar grains from varied sources in the nebula. Osmium in the Os(i) carrier is
      likely from nucleosynthetic sites with a neutron density about two to four times
      as high as that of the average solar s-process Os.

PMID- 16109879
TI  - The illusion of invariant quantities in life histories.
AB  - Life-history theory attempts to provide evolutionary explanations for variations
      in the ways in which animal species live their lives. Recent analyses have
      suggested that the dimensionless ratios of several key life-history parameters
      are the same for different species, even across distant taxa. However, we show
      here that previous analyses may have given a false picture and created an
      illusion of invariants, which do not necessarily exist; essentially, this is
      because life-history variables have been regressed against themselves. The
      following question arises from our analysis: How do we identify an invariant?

PMID- 16109880
TI  - Genome streamlining in a cosmopolitan oceanic bacterium.
AB  - The SAR11 clade consists of very small, heterotrophic marine alpha-proteobacteria
      that are found throughout the oceans, where they account for about 25% of all
      microbial cells. Pelagibacter ubique, the first cultured member of this clade,
      has the smallest genome and encodes the smallest number of predicted open reading
      frames known for a free-living microorganism. In contrast to parasitic bacteria
      and archaea with small genomes, P. ubique has complete biosynthetic pathways for
      all 20 amino acids and all but a few cofactors. P. ubique has no pseudogenes,
      introns, transposons, extrachromosomal elements, or inteins; few paralogs; and
      the shortest intergenic spacers yet observed for any cell.

PMID- 16109881
TI  - Contact-dependent inhibition of growth in Escherichia coli.
AB  - Bacteria have developed mechanisms to communicate and compete with each other for
      limited environmental resources. We found that certain Escherichia coli,
      including uropathogenic strains, contained a bacterial growth-inhibition system
      that uses direct cell-to-cell contact. Inhibition was conditional, dependent upon
      the growth state of the inhibitory cell and the pili expression state of the
      target cell. Both a large cell-surface protein designated Contact-dependent
      inhibitor A (CdiA) and two-partner secretion family member CdiB were required for
      growth inhibition. The CdiAB system may function to regulate the growth of
      specific cells within a differentiated bacterial population.

PMID- 16109882
TI  - Mitogenic influence of human R-spondin1 on the intestinal epithelium.
AB  - Several described growth factors influence the proliferation and regeneration of
      the intestinal epithelium. Using a transgenic mouse model, we identified a human
      gene, R-spondin1, with potent and specific proliferative effects on intestinal
      crypt cells. Human R-spondin1 (hRSpo1) is a thrombospondin domain-containing
      protein expressed in enteroendocrine cells as well as in epithelial cells in
      various tissues. Upon injection into mice, the protein induced rapid onset of
      crypt cell proliferation involving beta-catenin stabilization, possibly by a
      process that is distinct from the canonical Wnt-mediated signaling pathway. The
      protein also displayed efficacy in a model of chemotherapy-induced intestinal
      mucositis and may have therapeutic application in gastrointestinal diseases.

PMID- 16109883
TI  - The P2Y14 receptor of airway epithelial cells: coupling to intracellular Ca2+ and
      IL-8 secretion.
AB  - Uridine nucleotides and UDP-glucose are endogenous molecules, which are released
      into the extracellular environment in a lytic manner after cell damage, as well
      as by regulated nonlytic mechanisms. Recently, a UDP-glucose-specific G(i)
      protein-coupled P2Y receptor, namely P2Y(14), has been cloned. In this study, we
      demonstrated expression of the P2Y(14) mRNA in human lung epithelial cells and in
      the epithelial cell lines A549 and BEAS-2B. Evidence of functional expression of
      the P2Y(14) receptor in these cell lines was provided by calcium measurements
      after stimulation with uridine 5'-diphosphoglucose (UDP-glc). Experiments with
      pertussis toxin and the Ca(2+)-chelator EGTA revealed participation of pertussis
      toxin-sensitive G(i/o)-proteins in the mobilization of Ca(2+)-ions from
      intracellular stores by UDP-glc. Moreover, UDP-glc increased secretion of the
      potent neutrophil chemoattractant CXCL8/IL-8 in A549 and BEAS-2B cells in a
      pertussis toxin-sensitive manner. Moreover, reverse transcription and
      quantitative polymerase chain reaction revealed that UDP-glc modulated mRNA
      levels of IL-8/CXCL8. However, stimulation of A549 and BEAS-2B cells with UDP-glc
      neither modified basal nor cytokine-induced secretion of the CXC-chemokines
      CXCL9/MIG, CXCL10/IP-10, and CXCL11/I-TAC. In addition, UDP-glc did not affect
      proliferation of the two cell lines. In summary, our data provide evidence for a
      distinct physiologic role of P2Y(14) in the selective release of specific
      chemokines from human airway epithelial cells.

PMID- 16109884
TI  - HIV impairs TNF-alpha release in response to Toll-like receptor 4 stimulation in
      human macrophages in vitro.
AB  - The molecular mechanisms for increased risk of bacterial pneumonia in HIV+
      persons remain incompletely understood. Recognizing the critical role of Toll
      like receptor (TLR) signaling in host defense, this study showed that human U937
      macrophage stimulation by the TLR4-specific ligand, lipid A (biologically active
      component of bacterial LPS), promoted TNF-alpha release through extracellular
      regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase phosphorylation.
      In contrast, HIV+ U1 macrophages had significantly reduced TNF-alpha release
      (despite preserved TLR4 expression) and reduced ERK1/2 phosphorylation, whereas
      TNF-alpha release was intact via a TLR4-independent pathway. In HIV+ U1 cells,
      reduced ERK1/2 phosphorylation was not due to reduced upstream MEK1/2 activation,
      but was associated with a reciprocal induction of MAP kinase phosphatase-1 (MKP
      1). HIV nef protein was sufficient to reduce TNF-alpha release and induce MKP-1
      in healthy macrophages. Pharmacologic inhibition of endogenous cellular
      phosphatases increased ERK1/2 phosphorylation and partially restored TLR4
      mediated TNF-alpha release in HIV+ macrophages. Furthermore, targeted gene
      silencing of MKP-1 partially restored lipid A-mediated TNF-alpha release in HIV+
      U1 cells. Similar results were observed using clinically relevant human alveolar
      macrophages, comparing healthy to asymptomatic HIV+ persons at clinical risk for
      bacterial pneumonia. Thus, reduced TLR4-mediated TNF-alpha release through
      altered ERK1/2 regulation by HIV may impair an effective innate immune response
      to bacterial challenge. Inhibition of cellular phosphatases may serve as a
      potential therapeutic target in the management of bacterial pneumonia in HIV+
      persons.

PMID- 16109885
TI  - Assessing physiological complexity.
AB  - Physiologists both admire and fear complexity, but we have made relatively few
      attempts to understand it. Inherently complex systems are more difficult to study
      and less predictable. However, a deeper understanding of physiological systems
      can be achieved by modifying experimental design and analysis to account for
      complexity. We begin this essay with a tour of some mathematical views of
      complexity. After briefly exploring chaotic systems, information theory and
      emergent behavior, we reluctantly conclude that, while a mathematical view of
      complexity provides useful perspectives and some narrowly focused tools, there
      are too few generally practical take-home messages for physiologists studying
      complex systems. Consequently, we attempt to provide guidelines as to how complex
      systems might be best approached by physiologists. After describing complexity
      based on the sum of a physiological system's structures and processes, we
      highlight increasingly refined approaches based on the pattern of interactions
      between structures and processes. We then provide a series of examples
      illustrating how appreciating physiological complexity can improve physiological
      research, including choosing experimental models, guiding data collection,
      improving data interpretations and constructing more rigorous system models.
      Finally, we conclude with an invitation for physiologists, applied mathematicians
      and physicists to collaborate on describing, studying and learning from studies
      of physiological complexity.

PMID- 16109886
TI  - Generalization of convex shapes by bees: what are shapes made of?
AB  - For about 70 years, bees were assumed not to possess the capacity to discriminate
      among convex shapes, such as a disc, a square or a triangle, based on results of
      early studies conducted by presenting shapes on horizontal planes. Using shapes
      presented on a vertical plane, we recently demonstrated that bees do discriminate
      among a variety of convex shapes. Several findings, summarized here, provide
      indirect evidence that discrimination is based on a cue located at the shapes'
      boundaries. In the present study, we test this hypothesis directly in two
      different ways. (1) Three groups of bees are each trained with a different pair
      of convex shapes, one positive (rewarding), the other not (negative), producing
      colour contrast, luminance contrast or motion contrast against the background.
      The trained bees are then offered a choice between pairs of stimuli whose shapes
      are identical to those of the training shapes, but whose contrast against the
      background is varied by changing the pattern, the colour or the luminance of the
      areas. The results show that bees discriminate between the pairs of novel shapes,
      i.e. they generalize the shapes among the different types of contrast, revealing
      that they use a particular cue extracted from the positive shape. The bees'
      choices between a stimulus that produces the correct contrast but has the wrong
      shape and one that possesses the correct shape but the wrong contrast show, in
      addition, that the relevant cue is not located within the area of the shape. (2)
      Bees trained with pairs of convex shapes are tested with the same pairs of
      shapes, but which lack the inner area, i.e. only the contours or fragments of the
      contours are presented in the tests. Bees are found to prefer the stimulus whose
      contours (or fragments of contours) agree with those of the positive training
      shape. Taken together, the results suggest that convex shapes are not represented
      by the form of their areas but rather by some cue located at their boundaries.

PMID- 16109887
TI  - Muscle fiber angle, segment bulging and architectural gear ratio in segmented
      musculature.
AB  - The anatomical complexity of myomeres and myosepta has made it difficult to
      develop a comprehensive understanding of the relationship between muscle fiber
      architecture, connective tissue mechanics, and locomotor function of segmented
      axial musculature in fishes. The lateral hypaxial musculature (LHM) of
      salamanders is less anatomically complex and therefore a good system for
      exploring the basic mechanics of segmented musculature. Here, we derive a
      mathematical model of the LHM and test our model using sonomicrometry and
      electromyography during steady swimming in an aquatic salamander, Siren
      lacertina. The model predicts longitudinal segment strain well, with predicted
      and measured values differing by less than 5% strain over most of the range.
      Deviations between predicted and measured results are unbiased and probably
      result from the salamanders performing slight turns with associated body torsion
      in our unconstrained trackway swimming experiments. Model simulations of muscle
      fiber contraction and segment shortening indicate that longitudinal segment
      strain, for a given amount of muscle fiber strain, increases with increasing
      initial fiber angle. This increase in architectural gear ratio (AGR =
      longitudinal strain/fiber strain) is mediated by muscle fiber rotation; the
      higher the initial fiber angle, the more the fibers rotate during contraction and
      the higher the AGR. Muscle fiber rotation is additionally impacted by bulging in
      the dorsoventral (DV) and/or mediolateral (ML) dimensions during longitudinal
      segment shortening. In segments with obliquely oriented muscle fibers, DV bulging
      increases muscle fiber rotation, thereby increasing the AGR. Extending the model
      to include force and work indicates that force decreases with increasing initial
      muscle fiber angle and increasing DV bulging and that both longitudinal
      shortening and DV bulging must be included for accurate calculation of segment
      work.

PMID- 16109888
TI  - Carbonic anhydrase in the adult mosquito midgut.
AB  - We have previously demonstrated the involvement of carbonic anhydrase (CA) in
      larval mosquito midgut physiology. In this study, we used Hansson's
      histochemistry to examine the distribution of the enzyme in the midgut of Aedes
      aegypti, Aedes albopictus, Culex quinquefasciatus, Culex nigripalpus,
      Ochlerotatus taeniorhynchus, Anopheles albimanus and Anopheles quadrimaculatus
      adult mosquitoes. Additionally, we quantitated CA content in the anterior and
      posterior midgut of adult males and females from these species using the 18O
      isotope exchange method coupled to mass spectrometry. We also tested the effect
      of CA inhibitors such as methazolamide and acetazolamide in the alkalization of
      the midgut in females from these species. Our results indicate that CA is present
      in the midgut of adults from the species studied and that it appears to be
      preferentially associated with the posterior midgut in both males and females. CA
      inhibitors appear to have a profound effect on midgut pH indicating that this
      enzyme might play a key role in the maintenance of this pH.

PMID- 16109889
TI  - Sarcomere length measurement permits high resolution normalization of muscle
      fiber length in architectural studies.
AB  - The use of sarcomere length to normalize fiber length in architectural studies is
      commonly practiced but has not been explicitly validated. Using mouse hindlimb
      muscles as a model system, ankle joints were intentionally set to angles ranging
      from 30 degrees to 150 degrees and their muscles fixed. Tibialis anterior (TA),
      extensor digitorum longus (EDL) and soleus muscles were removed and their raw
      fiber length measured. Sarcomere length was then measured for each fiber length
      sample and fiber length was normalized to a standard sarcomere length. As
      expected, raw fiber length was dependent on tibiotarsal angle (P < 0.0005 for all
      muscles, r2 range 0.22-0.61), while sarcomere length normalization eliminated the
      joint-angle dependent variation in fiber length (P > 0.24, r2 range 0.001-0.028).
      Similarly, one-way ANOVA revealed no significant differences in normalized fiber
      length among ankle angles for any of the three muscles (P > 0.1), regardless of
      animal size. To determine the resolution of the method, power calculations were
      performed. For all muscles studied, there was >90% chance of detecting a 15%
      fiber length difference among muscles and >60% chance of detecting fiber length
      differences as small as 10%. We thus conclude that the use of sarcomere length
      normalization in architectural studies permits resolution of fiber length
      variations of 15% and may even be effective at resolving 10% fiber length
      variations.

PMID- 16109890
TI  - Mosquito natriuretic peptide identified as a calcitonin-like diuretic hormone in
      Anopheles gambiae (Giles).
AB  - Mosquito natriuretic peptide (MNP), an uncharacterised peptide from the yellow
      fever mosquito, Aedes aegypti, acts via cyclic AMP to stimulate secretion of Na+
      rich urine by opening a Na+ conductance in the basolateral membrane of Malpighian
      tubule principal cells. Corticotropin releasing factor (CRF)-related peptides and
      calcitonin (CT)-like diuretic peptides use cyclic AMP as a second messenger and
      were therefore considered likely candidates for MNP. BLAST searches of the genome
      of the malaria mosquito Anopheles gambiae, gave sequences for the CRF-related
      peptide Anoga-DH44 and the CT-like peptide Anoga-DH31, which were synthesised and
      tested for effects on Malpighian tubules from An. gambiae and Ae. aegypti,
      together with 8-bromo-cyclic AMP. The cyclic AMP analogue stimulated secretion of
      Na+-rich urine by An. gambiae Malpighian tubules, reproducing the response to MNP
      in Ae. aegypti. It also depolarised the principal cell basolateral membrane
      voltage (Vb) while hyperpolarising the transepithelial voltage (Vt) to a similar
      extent. Anoga-DH4) and Anoga-DH31 stimulated production of cyclic AMP, but not
      cyclic GMP, by Malpighian tubules of An. gambiae. Both peptides had diuretic
      activity, but only Anoga-DH31 had natriuretic activity and stimulated fluid
      secretion to the same extent as 8-bromo-cyclic AMP. Likewise, Anoga-DH31
      reproduced the effects of cyclic AMP on tubule electrophysiology, whereas Anoga
      DH44 initially hyperpolarised Vb and depolarised Vt, which is the opposite of the
      effect of Anoga-DH31. Anoga-DH44 and Anoga-DH31 were also tested for effects on
      fluid secretion and ion transport by Ae. aegypti tubules. As in An. gambiae, the
      CRF-related peptide Anoga-DH44 had a non-specific effect on the transport of Na+
      and K+, whereas the CT-like peptide Anoga-DH31 specifically stimulated
      transepithelial Na+ transport. We conclude that the CT-like peptide Anoga-DH31 is
      the previously uncharacterised mosquito natriuretic peptide.

PMID- 16109891
TI  - Performance of guinea fowl Numida meleagris during jumping requires storage and
      release of elastic energy.
AB  - The ability of birds to perform effective jumps may play an important role in
      predator avoidance and flight initiation. Jumping can provide the vertical
      acceleration necessary for a rapid takeoff, which may be particularly important
      for ground-dwelling birds such as phasianids. We hypothesized that by making use
      of elastic energy storage and release, the leg muscles could provide the large
      power outputs needed for achieving high velocities after takeoff. We investigated
      the performance of the leg muscles of the guinea fowl Numida meleagris during
      jumping using kinematic and force-plate analyses. Comparison of the methods
      indicated that in this species the wings did not supply energy to power takeoff
      and thus all the work and power came from the leg muscles. Guinea fowl produced a
      peak vertical force of 5.3 times body weight. Despite having lower muscle-mass
      specific power output in comparison to more specialized jumpers, guinea fowl
      demonstrated surprisingly good performance by producing muscle-mass-specific work
      outputs of 45 J kg(-1), a value approximately two thirds of the maximal expected
      value for skeletal muscle. The muscle-mass-specific peak power output during
      jumping was nearly 800 W kg(-1), which is more than twice the peak isotonic power
      estimated for guinea fowl leg muscles. To account for high power outputs, we
      concluded that energy has to be stored early in the jumps and released later
      during peak power production, presumably using mechanisms similar to those found
      in more specialized jumpers.

PMID- 16109892
TI  - Identification and characterization of a tachykinin-containing neuroendocrine
      organ in the commissural ganglion of the crab Cancer productus.
AB  - A club-shaped, tachykinin-immunopositive structure first described nearly two
      decades ago in the commissural ganglion (CoG) of three species of decapod
      crustaceans has remained enigmatic, as its function is unknown. Here, we use a
      combination of anatomical, mass spectrometric and electrophysiological techniques
      to address this issue in the crab Cancer productus. Immunohistochemistry using an
      antibody to the vertebrate tachykinin substance P shows that a homologous site
      exists in each CoG of this crab. Confocal microscopy reveals that its structure
      and organization are similar to those of known neuroendocrine organs. Based on
      its location in the anterior medial quadrant of the CoG, we have named this
      structure the anterior commissural organ (ACO). Matrix-assisted laser
      desorption/ionization Fourier transform mass spectrometry shows that the ACO
      contains the peptide APSGFLGMRamide, commonly known as Cancer borealis tachykinin
      related peptide Ia (CabTRP Ia). Using the same technique, we show that CabTRP Ia
      is also released into the hemolymph. As no tachykinin-like labeling is seen in
      any of the other known neuroendocrine sites of this species (i.e. the sinus
      gland, the pericardial organ and the anterior cardiac plexus), the ACO is a prime
      candidate to be the source of CabTRP Ia present in the circulatory system. Our
      electrophysiological studies indicate that one target of hemolymph-borne CabTRP
      Ia is the foregut musculature. Here, no direct CabTRP Ia innervation is present,
      yet several gastric mill and pyloric muscles are nonetheless modulated by
      hormonally relevant concentrations of the peptide. Collectively, our findings
      show that the C. productus ACO is a neuroendocrine organ providing hormonal
      CabTRP Ia modulation to the foregut musculature. Homologous structures in other
      decapods are hypothesized to function similarly.

PMID- 16109893
TI  - Hypoxia progressively lowers thermal gaping thresholds in bearded dragons, Pogona
      vitticeps.
AB  - Most animals, including reptiles, lower body temperature (Tb) under hypoxic
      conditions. Numerous physiological and behavioural traits significant to the
      regulation of Tb are altered by hypoxia in ways that suggest an orchestrated
      adjustment of Tb at a new and lower regulated level. We examined this matter in
      bearded dragons, Pogona vitticeps, a species of reptile that naturally exhibits
      open mouth gaping at high temperatures, presumably in order to promote
      evaporation and thus prevent or avoid further increases in Tb. The threshold for
      the onset of gaping (assessed as the temperature at which lizards spent 50% of
      their time gaping) was reduced from 36.9 degrees C in normoxia to 35.5 degrees C
      at 10% and 34.3 degrees C at 6% O2. The overall magnitude or degree of gaping,
      measured qualitatively, was more pronounced at lower temperatures in hypoxia.
      Females consistently had lower gaping threshold temperatures than did males, and
      this difference was retained throughout exposure to hypoxia. In addition to
      gaping, evaporative water loss from the cloaca may also play a significant role
      in temperature regulation, since the ambient temperature at which cloacal
      discharge occurred was also reduced significantly in hypoxia. The results
      reported herein strongly support the view that hypoxia reduces temperature set
      point in lizards and that such changes are coordinated by specific behavioural
      thermoeffectors that modulate evaporative water loss and thus facilitate a high
      potential for controlling or modifying Tb.

PMID- 16109894
TI  - Terrestrial locomotion does not constrain venous return in the American
      alligator, Alligator mississippiensis.
AB  - The effects of treadmill exercise on components of the cardiovascular (heart
      rate, mean arterial blood pressure, central venous pressure, venous return) and
      respiratory (minute ventilation, tidal volume, breathing frequency, rate of
      oxygen consumption, rate of carbon dioxide production) systems and on intra
      abdominal pressure were measured in the American alligator, Alligator
      mississippiensis, at 30 degrees C. Alligators show speed-dependent increases in
      tidal volume and minute ventilation, demonstrating that the inhibition of
      ventilation during locomotion that is present in some varanid and iguanid lizards
      was not present in alligators. Exercise significantly increases intra-abdominal
      pressure; however, concomitant elevations in central venous pressure acted to
      increase the transmural pressure of the post caval vein and thus increased venous
      return. Therefore, despite elevated intra-abdominal pressure, venous return was
      not limited during exercise in alligators, as was the case in Varanus
      exanthematicus and Iguana iguana. Respiratory cycle variations in intra-abdominal
      pressure, central venous pressure and venous return indicate that, at high tidal
      volumes, inspiration causes a net reduction in venous return during active
      ventilation and thus may act to limit venous return during exercise. These
      results suggest that, while tonically elevated intra-abdominal pressure induced
      by exercise does not inhibit venous return, phasic fluctuations during each
      breath cycle may contribute to venous flow limitation during exercise.

PMID- 16109896
TI  - Evolving neural models of path integration.
AB  - We use a genetic algorithm to evolve neural models of path integration, with
      particular emphasis on reproducing the homing behaviour of Cataglyphis fortis
      ants. This is done within the context of a complete model system, including an
      explicit representation of the animal's movements within its environment. We show
      that it is possible to produce a neural network without imposing a priori any
      particular system for the internal representation of the animal's home vector.
      The best evolved network obtained is analysed in detail and is found to resemble
      the bicomponent model of Mittelstaedt. Because of the presence of leaky
      integration, the model can reproduce the systematic navigation errors found in
      desert ants. The model also naturally mimics the searching behaviour that ants
      perform once they have reached their estimate of the nest location. The results
      support possible roles for leaky integration and cosine-shaped compass response
      functions in path integration.

PMID- 16109895
TI  - Role of biogenic amines and cHH in the crustacean hyperglycemic stress response.
AB  - In this study, we investigated (using bioassays and ELISA) the variation of cHH
      (crustacean hyperglycemic hormone) level in the eyestalks and hemolymph of
      Palaemon elegans (Rathke) (Decapoda, Caridea) following injection of serotonin (5
      HT) and dopamine (DA) and correlated cHH profile with the variation in amount and
      time course of glycemia. 5-HT induced in P. elegans a rapid and massive release
      of cHH from the eyestalk into the hemolymph followed by hyperglycemia. On the
      contrary, DA did not significantly affect cHH release and hyperglycemia. In
      addition, we measured the level and variation of 5-HT in the eyestalk and
      hemolymph of P. elegans following copper contamination. The release of 5-HT from
      the eyestalk is very rapid and dose dependent. In the hemolymph, a peak of 5-HT
      occurs after 30 min, and again the circulating concentration of 5-HT is dose
      dependent on copper exposure. After 1 h, the level of 5-HT slowly decreases to
      basal level. The release of 5-HT from the eyestalk into the hemolymph after
      copper exposure precedes the release of cHH, confirming its role as a
      neurotransmitter acting on cHH neuroendocrine cells. The fact that copper induced
      a rapid and massive release of 5-HT from the eyestalk can explain its
      demonstrated role in inducing the release of cHH and the consequent hyperglycemia
      in intact but not eyestalkless animals.

PMID- 16109897
TI  - Hind limb proportions and kinematics: are small primates different from other
      small mammals?
AB  - Similar in body size, locomotor behaviour and morphology to the last common
      ancestor of Primates, living small quadrupedal primates provide a convenient
      model for investigating the evolution of primate locomotion. In this study, the
      hind limb kinematics of quadrupedal walking in mouse lemurs, brown lemurs, cotton
      top tamarins and squirrel monkeys are analysed using cineradiography. The scaling
      of hind limb length to body size and the intralimb proportions of the three
      segmented hind limb are taken into consideration when kinematic similarities and
      differences are discussed. Hind limb kinematics of arboreal quadrupedal primates,
      ranging in size between 100 g and 3000 g, are size independent and resemble the
      hind limb kinematics of small non-cursorial mammals. A common feature seen in
      smaller mammals, in general, is the horizontal position of the thigh at touchdown
      and of the lower leg at lift-off. Thus, the maximum bone length is immediately
      transferred into the step length. The vertical position of the leg at the
      beginning of a step cycle and of the thigh at lift-off contributes the same
      distance to pivot height. Step length and pivot height increase proportionally
      with hind limb length, because intralimb proportions of the hind limb remain
      fairly constant. Therefore, the strong positive allometric scaling of the hind
      limb in arboreal quadrupedal primates affects neither the kinematics of hind limb
      segments nor the total angular excursion of the limb. The angular excursion of
      the hind limb in quadrupedal primates is equal to that of other non-cursorial
      mammals. Hence, hind limb excursion in larger cercopithecine primates differs
      from that of other large mammals due to the decreasing angular excursion as part
      of convergent cursorial adaptations in several phylogenetic lineages of mammals.
      Typical members of those phylogenetic groups are traditionally used in comparison
      with typical primates, and therefore the ;uniqueness' of primate locomotor
      characteristics is often overrated.

PMID- 16109898
TI  - Spatial orientation in echolocating harbour porpoises (Phocoena phocoena).
AB  - Studies concerning the echolocation behaviour of odontocetes focus mainly on
      target detection and discrimination, either in stationary animals or in animals
      approaching a specific target. We present the first data on the use of
      echolocation for spatial orientation or navigation. Synchronised video and high
      frequency recordings were made of two harbour porpoises trained to swim from one
      position to another across an outdoor pool in order to correlate swimming and
      echolocation behaviour. Both porpoises showed a clear range-locking behaviour on
      specific positions near the end of the pool, as indicated by a decrease in click
      interval with decreasing distance. The decrease in click interval followed the
      two-way-transit time, which is the time interval between the outgoing click and
      the received echo from the focal object. This suggests that the porpoises used
      focal objects as landmarks. The lag time, defined as the time between the arrival
      of an echo from a landmark and the emission of the next click, was task specific.
      The lag time was longer for difficult tasks (26-36 ms) and shorter for simpler
      tasks (14-19 ms), with some individual differences between the two animals. Our
      results suggest that echolocation by odontocetes is used not only for target
      detection, localisation and classification but also for spatial orientation.

PMID- 16109899
TI  - The kinematics of feeding and drinking in palaeognathous birds in relation to
      cranial morphology.
AB  - Cranial kinesis is an important feature in avian feeding behaviour and involves
      the transmission of quadrate movement to the upper bill by the Pterygoid
      Palatinum Complex (PPC). The PPC in Palaeognathae is remarkably different from
      that found in Neognathae. In this study we analyse whether the special morphology
      of the PPC is an adaptation to the feeding behaviour of the Palaeognathae.
      Behavioural analyses of the rhea Rhea americana showed that the feeding behaviour
      of the rhea is typical ;Catch and Throw' behaviour, independent of the size of
      the food item. Drinking is achieved by a scooping movement followed by a low
      amplitude tip-up phase. During feeding rhynchokinetic movements of the upper bill
      were observed. However, cranial kinesis was limited and may differ from
      rhynchokinesis in neognathes as a clear bending zone seemed absent. Since the
      movement patterns are considered very similar to the basic feeding behaviour in
      neognathous birds it is concluded that the specific morphology of the PPC is not
      the result of specific functional demands from palaeognathous feeding behaviour.

PMID- 16109900
TI  - Cranial kinesis in palaeognathous birds.
AB  - Cranial kinesis in birds is induced by muscles located caudal on the cranium.
      These forces are transferred onto the moveable parts of the skull via the
      Pterygoid-Palatinum Complex (PPC). This bony structure therefore plays an
      essential role in cranial kinesis. In palaeognathous birds the morphology of the
      PPC is remarkably different from that of neognathous birds and is thought to be
      related to the specific type of cranial kinesis in palaeognaths known as central
      rhynchokinesis. We determined whether clear bending zones as found in neognaths
      are present in the upper bill of paleognaths, and measured bending forces
      opposing elevation of the upper bill. A static force model was used to calculate
      the opening forces that can be produced by some of the palaeognathous species. We
      found that no clear bending zones are present in the upper bill, and bending is
      expected to occur over the whole length of the upper bill. Muscle forces are more
      than sufficient to overcome bending forces and to elevate the upper bill. The
      resistance against bending by the bony elements alone is very low, which might
      indicate that bending of bony elements can occur during food handling when
      muscles are not used to stabilise the upper bill. Model calculations suggest that
      the large processi basipterygoidei play a role in stabilizing the skull elements,
      when birds have to resist external opening forces on the upper bill as might
      occur during tearing leafs from plants. We conclude that the specific morphology
      of the palaeognathous upper bill and PPC are not designed for active cranial
      kinesis, but are adapted to resist external forces that might cause unwanted
      elevation of the upper bill during feeding.

PMID- 16109901
TI  - Mechanisms underlying the production of carapace vibrations and associated
      waterborne sounds in the American lobster, Homarus americanus.
AB  - American lobsters produce carapace vibrations, which also lead to waterborne
      acoustic signals, by simultaneously contracting the antagonistic remotor and
      promotor muscles located at the base of the second antenna. These vibrations have
      a mean frequency of 183.1 Hz (range 87-261 Hz), range in duration from 68 to 1720
      ms (mean 277.1 ms) and lead to waterborne sounds of similar frequencies. Lobsters
      most often produce these signals using only one pair of muscles at a time and
      alternate between the muscles of the left and right antennae when making a series
      of vibrations. Occasionally, they vibrate their carapace by simultaneously
      contracting both sets of muscles. While the remotor muscle is required for
      producing carapace vibrations, the promotor appears to play a secondary role.
      Electrical stimulation of the remotor, but not the promotor, results in the
      production of vibrations, while lesions of the remotor, but not promotor,
      eliminate the ability of lobsters to vibrate their carapace. Lobsters of all
      sizes and both sexes produce these signals when startled, grasped or threatened.
      However, at this time, the behavioral significance of vibration and/or sound
      production by American lobsters is not known.

PMID- 16109902
TI  - Plasma adiponectin levels and five-year survival after first-ever ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: This study aimed to investigate the association between
      plasma adiponectin levels and 5-year survival after first-ever ischemic stroke.
      METHODS: Plasma adiponectin measured within 24 hours after first-ever ischemic
      stroke was related to 5-year outcome. The Kaplan-Meier technique was applied in
      survival analysis, and the Cox proportional hazards model was used to evaluate
      the relationship between risk factors and prognosis. RESULTS: The probabilities
      of death were 92.8%, 52.5%, and 10.5% (P<0.001) for patients stratified according
      to tertiles of adiponectin (<4 microg/mL, 4 to 7 microg/mL, and >7 microg/mL,
      respectively). The relative risk of death was 8.1 (95% CI, 3.1, 24.5; P<0.001)
      for individuals with adiponectin levels in the lowest tertile compared with the
      upper tertile. Adiponectin <4 microg/mL (hazard ratio [HR], 5.2; 95% CI, 2.1,
      18.4; P<0.001), score >15 in the National Institutes of Health Stroke Scale (HR,
      3.6; 95% CI, 1.7, 15.9; P<0.001), and coronary heart disease (HR, 2.9; 95% CI,
      1.5, 12.3; P<0.001) were independently associated with mortality. CONCLUSIONS:
      Low plasma adiponectin is related to an increased risk of 5-year mortality after
      first-ever ischemic stroke, independently of other adverse predictors.

PMID- 16109904
TI  - Ischemic stroke subtypes and thrombophilia in young and elderly Brazilian stroke
      patients admitted to a rehabilitation hospital.
AB  - BACKGROUND AND PURPOSE: We sought to examine ischemic stroke subtypes and
      prevalence of thrombophilia in Brazilian stroke patients. METHOD: A total of 130
      consecutive young and 200 elderly stroke patients were studied. RESULTS:
      Prevalence of thrombophilia was, respectively: protein S deficiency (11.5% versus
      5.5%), protein C deficiency (0.76% versus 1%), resistance to activated protein C
      (2.3% versus 3.5%), mutation in V Leiden factor (1.5% versus 2%), antithrombin
      III deficiency (0% versus 0%), lupus anticoagulant (0% versus 0.5%),
      anticardiolipin antibodies (3% versus 10%; P=0.01), hyperhomocysteinemia (31.5%
      versus 53.5%; P=0.0001), mutation of the MTHFR gene in homocigosis (10% versus
      5%), and heterocigosis (27.6% versus 41.9%; P=0.01). CONCLUSIONS: Prothrombotic
      conditions were more frequent in stroke of undetermined cause.

PMID- 16109905
TI  - Long-term effect of shock wave therapy on upper limb hypertonia in patients
      affected by stroke.
AB  - BACKGROUND AND PURPOSE: Spasticity is a disabling complication of stroke and
      different noninvasive treatments are used to reduce muscle hypertonia. Shock
      waves are defined as a sequence of single sonic pulses largely used in the
      treatment of diseases involving bone and tendon as well as muscular contractures.
      The effect and duration of extracorporeal shock wave therapy (ESWT) was
      investigated on muscle hypertonia of the hand and wrist. METHODS: A total of 20
      patients affected by stroke associated with severe hypertonia in upper limbs were
      evaluated. Placebo stimulation was performed 1 week before active stimulation in
      each patient. Evaluation was performed using the National Institutes of Health
      and Ashworth scales and video monitoring with a digital goniometer before and
      immediately after placebo or active stimulation. Motor nerve conduction velocity
      from abductor digiti minimi were recorded. Patients were monitored at 1, 4, and
      12 weeks after active treatment. RESULTS: After active ESWT, patients showed
      greater improvement in flexor tone of wrist and fingers compared with placebo
      stimulation. At the 1- and 4-week follow-up visits, a significant decrease of
      passive muscle tonicity was noted on muscles in all patients receiving active
      treatment. At 12 weeks after therapy, 10 of the 20 patients showed persistent
      reduction in muscle tone. There were no adverse events associated with ESWT.
      CONCLUSIONS: ESWT reduces hypertonia of the wrist and finger muscles for > or =12
      weeks after treatment. The possible mechanisms of action of ESWT are discussed.

PMID- 16109906
TI  - Elevated tumor necrosis factor-alpha in skeletal muscle after stroke.
AB  - BACKGROUND AND PURPOSE: Tumor necrosis factor-alpha (TNF-alpha), an inflammatory
      cytokine negligibly expressed in normal muscle, is elevated in selected metabolic
      conditions characterized by muscle wasting and insulin resistance. Inflammation
      is fundamental to stroke pathogenesis. Stroke patients have gross muscular
      atrophy and high prevalence of diabetes and insulin resistance. Yet, no previous
      studies examined TNF-alpha expression in hemiparetic skeletal muscle. This study
      investigates whether TNF-alpha mRNA levels are elevated in paretic compared with
      nonparetic leg muscles of chronic ischemic stroke patients and age-matched
      controls. METHOD: Total RNA extracted from bilateral vastus lateralis muscle
      biopsies from n=20 hemiparetic stroke patients and n=9 healthy controls was
      reverse transcribed to cDNA, then TNF-alpha transcripts were amplified by real
      time quantitative polymerase chain reaction. TNF-alpha mRNA concentrations were
      normalized against acidic ribosomal phosphoprotein, housekeeping gene. RESULTS:
      TNF-alpha mRNA levels were 2.8-fold higher in paretic compared with control leg
      muscle (6.28+/-1.86 versus 2.28+/-0.67; P<0.03) and 1.6-fold higher in nonparetic
      leg (3.71+/-1.02; P<0.11) compared with controls. There was a trend for higher
      TNF-alpha mRNA in paretic compared with nonparetic leg. CONCLUSIONS: Findings
      demonstrate increased TNF-alpha expression in paretic leg muscle, suggesting
      inflammatory pathways are accelerated in stroke muscle. Further studies are under
      way to determine whether intramuscular TNF-alpha contributes to atrophy and
      metabolic abnormalities after stroke.

PMID- 16109907
TI  - Associations of the angiotensin II type 1 receptor A1166C and the endothelial NO
      synthase G894T gene polymorphisms with silent subcortical white matter lesions in
      essential hypertension.
AB  - BACKGROUND AND PURPOSE: Silent white matter lesions (WMLs) may represent early
      target organ damage of the brain in patients with hypertension. Because these
      lesions may have a genetic background, we assessed the associations between
      polymorphisms of the renin-angiotensin system and the endothelial NO synthase
      (NOS3) genes and silent WMLs. METHODS: Ninety-three hypertensive individuals were
      studied. MRI of the brain was performed to obtain estimates of the total volume
      of subcortical and the extent of periventricular WMLs. Patients were genotyped
      for the angiotensinogen (M235T), the angiotensin-converting enzyme
      (insertion/deletion [I/D]), the angiotensin II type 1 receptor (AGTR1 A1166C),
      and the NOS3 (G894T) genes. A linear regression model was used to assess the
      relationship of these gene polymorphisms with both subtypes of WMLs. RESULTS:
      When adjusted for age, diabetes mellitus, and blood pressure, subcortical WML
      volume was lowest in the presence of 1 or 2 AGTR1 C alleles (unstandardized beta,
      -38.8 [95% CI, -66.1 to -11.4] and -112.6 [CI, -188.9 to -36.4], respectively),
      whereas it was highest in the presence of an NOS3 T allele (31.1[corrected] [CI,
      3.6 to 58.4]). No interaction between these polymorphisms on WMLs could be
      demonstrated. No associations were present with the other polymorphisms, either
      with subcortical or periventricular lesions. CONCLUSIONS: We found the AGTR1
      A1166C as well as the NOS3 G894T polymorphisms to be associated with silent WMLs
      in the subcortical area.

PMID- 16109908
TI  - Computerized arm training improves the motor control of the severely affected arm
      after stroke: a single-blinded randomized trial in two centers.
AB  - BACKGROUND AND PURPOSE: To compare a computerized arm trainer (AT), allowing
      repetitive practice of passive and active bilateral forearm and wrist movement
      cycle, and electromyography-initiated electrical stimulation (ES) of the paretic
      wrist extensor in severely affected subacute stroke patients. METHOD: A total of
      44 patients, 4 to 8 weeks after stroke causing severe arm paresis (Fugl-Meyer
      Motor Score [FM, 0 to 66] <18), were randomly assigned to either AT or ES. All
      patients practiced 20 minutes every workday for 6 weeks. AT patients performed
      800 repetitions per session with the robot and ES patients performed 60 to 80
      wrist extensions per session. The primary outcome measure was the blindly
      assessed FM (0 to 66), and the secondary measures were the upper limb muscle
      power (Medical Research Council [MRC] sum, 0 to 45) and muscle tone (Ashworth
      score sum, 0 to 25), assessed at the beginning and end of treatment and at 3
      month follow-up. RESULTS: The AT group had a higher Barthel Index score at
      baseline, but the groups were otherwise homogenous. As expected, FM and MRC sum
      scores improved overtime in both groups but significantly more in the robot AT
      group. The initial Barthel Index score had no influence. In the robot AT group,
      FM score was 15 points higher at study end and 13 points higher at 3-month follow
      up than the control ES group. MRC sum score was 15 points higher at study end and
      at 3-month follow-up compared with the control ES group. Muscle tone remained
      unchanged, and no side effects occurred. CONCLUSIONS: The computerized active arm
      training produced a superior improvement in upper limb motor control and power
      compared with ES in severely affected stroke patients. This is probably
      attributable to the greater number of repetitions and the bilateral approach.

PMID- 16109910
TI  - Extracranial arterial dissection: anticoagulation is the treatment of choice.

PMID- 16109909
TI  - Formal dysphagia screening protocols prevent pneumonia.
AB  - BACKGROUND: Pneumonia is an important complication of ischemic stroke and
      increases mortality 3-fold. Five guidelines recommend a dysphagia screen before
      oral intake. What constitutes an adequate dysphagia screen and which patients
      should receive it remain unclear. METHODS: Fifteen acute care institutions
      prospectively collected data on all admitted patients with acute ischemic stroke.
      Sites were required to collect data on demographics and 4 quality indicators.
      Optional data included stroke severity and complications. We measured adherence
      to a screen for dysphagia, the type of screen, and development of in-hospital
      pneumonia. RESULTS: Between December 2001 and January 2003, 2532 cases were
      collected. In-hospital complications were recorded on 2329 (92%) of cases. Stroke
      severity was captured on 1361 (54%). Adherence to a dysphagia screen was 61%. Six
      sites had a formal dysphagia screen, and their adherence rate was 78% compared
      with 57% at sites with no formal screen. The pneumonia rate at sites with a
      formal dysphagia screen was 2.4% versus 5.4% (P=0.0016) at sites with no formal
      screen. There was no difference in median stroke severity (5 versus 4; P=0.84)
      between the sites with and without a formal screen. A formal dysphagia screen
      prevented pneumonia even after adjusting for stroke severity. CONCLUSIONS: A
      formal dysphagia screen is associated with a higher adherence rate to dysphagia
      screens and a significantly decreased risk of pneumonia. A formal screening
      protocol should be offered to all stroke patients, regardless of stroke severity.

PMID- 16109911
TI  - Extracranial arterial dissection: anticoagulation is the treatment of choice:
      against.

PMID- 16109912
TI  - Extracranial arterial dissection: anticoagulation is the treatment of choice:
      for.

PMID- 16109917
TI  - Complement activation in angiotensin II-induced organ damage.
AB  - We tested whether or not complement activation participates in angiotensin (Ang)
      II-induced vasculopathy. We used double transgenic rats harboring human renin and
      angiotensinogen genes (dTGR) with or without losartan or the human renin
      inhibitor aliskiren. Sprague-Dawley (SD) rats were controls. DTGR had increased
      blood pressure at week 5 that increased further by week 7. Albuminuria was absent
      at week 5 but increased markedly in weeks 6 and 7. C-reactive protein (CRP)
      elevation, macrophages, T cells, tumor necrosis factor (TNF)-alpha, C1q, C3, C3c,
      and C5b-9 expression preceded albuminuria. C1q, C3, C3c, and C5b-9 were observed
      in the dTGR vessel media. C5b-9 colocalized with interleukin (IL)-6. Losartan and
      aliskiren reduced albuminuria and complement expression. We also studied vascular
      smooth muscle cells (VSMC) from dTGR compared VSMC from SD. C3 and IL-6 mRNA were
      analyzed after Ang II, TNF-alpha, and CRP stimulation. VSMC from dTGR showed
      increased proliferation and C3 expression compared with SD. Ang II did not induce
      C3 mRNA in either VSMC type. However, TNF-alpha and CRP induced C3 mRNA slightly
      in SD VSMC but markedly in dTGR VSMC, whereas IL-6 induction was similar in both.
      Thus, complement activation and cell infiltration occurred before the onset of
      albuminuria in Ang II-mediated renal damage. TNF-alpha and CRP played a major
      role in C3 activation. VSMC from dTGR are more sensitive for C3 activation. Our
      data show that, in this Ang II-induced model, complement activation is a major
      participant and suggest that TNF-alpha and CRP may play a role in its induction.

PMID- 16109918
TI  - Transgenic overexpression of vascular endothelial growth factor-B isoforms by
      endothelial cells potentiates postnatal vessel growth in vivo and in vitro.
AB  - Vascular endothelial growth factors (VEGFs) play significant roles in endothelial
      growth, survival, and function, and their potential use as therapeutic agents to
      promote the revascularization of ischemic tissues in being avidly explored. VEGF
      A has received most attention, as it is a potent stimulator of vascular growth.
      Results in clinical trials of VEGF-A as a therapeutic agent have fallen short of
      high expectations because of serious edematous side effects caused by its
      activity in promoting vascular permeability. VEGF-B, a related factor, binds some
      of the VEGF-A receptors but not to VEGF receptor 2, which is implicated in the
      vascular permeability promoting activity of VEGF-A. Despite little in vitro
      evidence to date for the ability of Vegf-B to directly promote angiogenesis,
      recent data indicate that it may promote postnatal vascular growth in mice,
      suggesting that it may have potential therapeutic application. We have
      specifically studied the effects of VEGF-B on vascular growth in vivo and on
      angiogenesis in vitro by analyzing transgenic mice in which individual isoforms
      (VEGFB167Tg and VEGFB186Tg) of VEGF-B are overexpressed in endothelial cells.
      VEGFB167Tg and VEGFB186Tg mice displayed enhanced vascular growth in the Matrigel
      assay in vivo and during cutaneous wound healing. In the aortic explant assay,
      explants from VEGFB167Tg and VEGFB186Tg mice displayed elevated vascular growth,
      suggesting a direct effect of VEGF-B isoforms in potentiating angiogenesis. These
      data support the use of VEGF-B as a therapeutic agent to promote vascular growth,
      in part, by potentiating angiogenesis. Furthermore, the lack of vascular
      permeability activity associated with either transgenic overexpression of the
      VEGF-B gene in endothelial cells or application of VEGF-B protein to the skin of
      mice in the Miles assay indicates that use of VEGF-B as a therapy should not be
      associated with edematous side effects.

PMID- 16109919
TI  - Targeting of a novel Ca+2/calmodulin-dependent protein kinase II is essential for
      extracellular signal-regulated kinase-mediated signaling in differentiated smooth
      muscle cells.
AB  - Subcellular targeting of kinases controls their activation and access to
      substrates. Although Ca2+/calmodulin-dependent protein kinase II (CaMKII) is
      known to regulate differentiated smooth muscle cell (dSMC) contractility, the
      importance of targeting in this regulation is not clear. The present study
      investigated the function in dSMCs of a novel variant of the gamma isoform of
      CaMKII that contains a potential targeting sequence in its association domain
      (CaMKIIgamma G-2). Antisense knockdown of CaMKIIgamma G-2 inhibited extracellular
      signal-related kinase (ERK) activation, myosin phosphorylation, and contractile
      force in dSMCs. Confocal colocalization analysis revealed that in unstimulated
      dSMCs CaMKIIgamma G-2 is bound to a cytoskeletal scaffold consisting of
      interconnected vimentin intermediate filaments and cytosolic dense bodies. On
      activation with a depolarizing stimulus, CaMKIIgamma G-2 is released into the
      cytosol and subsequently targeted to cortical dense plaques. Comparison of
      phosphorylation and translocation time courses indicates that, after CaMKIIgamma
      G-2 activation, and before CaMKIIgamma G-2 translocation, vimentin is
      phosphorylated at a CaMKII-specific site. Differential centrifugation
      demonstrated that phosphorylation of vimentin in dSMCs is not sufficient to cause
      its disassembly, in contrast to results in cultured cells. Loading dSMCs with a
      decoy peptide containing the polyproline sequence within the association domain
      of CaMKIIgamma G-2 inhibited targeting. Furthermore, prevention of CaMKIIgamma G
      2 targeting led to significant inhibition of ERK activation as well as
      contractility. Thus, for the first time, this study demonstrates the importance
      of CaMKII targeting in dSMC signaling and identifies a novel targeting function
      for the association domain in addition to its known role in oligomerization.

PMID- 16109920
TI  - Increased fibulin-5 and elastin in S100A4/Mts1 mice with pulmonary hypertension.
AB  - Transgenic mice overexpressing the calcium binding protein, S100A4/Mts1,
      occasionally develop severe pulmonary vascular obstructive disease. To understand
      what underlies this propensity, we compared the pulmonary vascular hemodynamic
      and structural features of S100A4/Mts1 with control C57Bl/6 mice at baseline,
      following a 2-week exposure to chronic hypoxia, and after 1 and 3 months
      "recovery" in room air. S100A4/Mts1 mice had greater right ventricular systolic
      pressure and right ventricular hypertrophy at baseline, which increased further
      with chronic hypoxia and was sustained after 3 months "recovery" in room air.
      These findings correlated with a heightened response to acute hypoxia and failure
      to vasodilate with nitric oxide or oxygen. S100A4/Mts1 mice, when compared with
      C57Bl/6 mice, also had impaired cardiac function judged by reduced ventricular
      elastance and decreased cardiac output. Despite higher right ventricular systolic
      pressures with chronic hypoxia, S100A4/Mts1 mice did not develop more severe PVD,
      but in contrast to C57Bl/6 mice, these features did not regress on return to room
      air. Microarray analysis of lung tissue identified a number of genes
      differentially upregulated in S100A4/Mts1 versus control mice. One of these,
      fibulin-5, is a matrix component necessary for normal elastin fiber assembly.
      Fibulin-5 was localized to pulmonary arteries and associated with thickened
      elastic laminae. This feature could underlie attenuation of pulmonary vascular
      changes in response to elevated pressure, as well as impaired reversibility.

PMID- 16109921
TI  - p47phox-dependent NADPH oxidase regulates flow-induced vascular remodeling.
AB  - Chronic alterations in blood flow elicit an adaptive response that tends to
      normalize shear stress, involving nitric oxide (NO) and matrix metalloproteinases
      (MMPs). To evaluate the role of NADPH oxidase in this process, we developed a new
      model of mouse arteriovenous fistula (AVF) connecting the right common carotid
      artery (RCCA) with the jugular vein, which does not affect blood pressure. Mice
      deficient for gp91phox and p47phox subunits of NADPH and wild-type controls were
      used. AVF greatly increased RCCA blood flow (0.78+/-0.12 to 4.71+/-0.78 mL/min;
      P<0.01), producing an abrupt rise in shear stress (35+/-1 to 261+/-17 dynes/cm2;
      P<0.01) within 24 hours. RCCA diameter (460+/-14 microm) gradually enlarged 1 and
      3 weeks after AVF (534+/-14 microm and 627+/-19 microm; P<0.01), reducing shear
      stress (173+/-13 and 106+/-10 dynes/cm2, respectively). In gp91phox(-/-) mice,
      changes in RCCA caliber and shear stress matched controls. However, p47phox(-/-)
      mouse RCCAs enlarged only marginally, such that shear stress remained high (199+/
      8 dynes/cm2 at 3 weeks). Likewise, remodeling was minimal in endothelial NO
      synthase (eNOS)(-/-) mice. In both control and gp91phox(-/-) animals, reactive
      oxygen species (ROS) production and MMP induction was enhanced by AVF, whereas in
      p47phox(-/-) and eNOS(-/-) mice such response was negligible. Similarly,
      nitrotyrosine staining, indicating peroxynitrite formation, was more pronounced
      in control and gp91phox(-/-) mice than in p47phox(-/-) and eNOS(-/-) mice. Hence,
      shear stress induces vascular NADPH oxidase comprising p47phox but not gp91phox.
      Generated ROS interact with NO to produce peroxynitrite, which in turn activates
      MMPs, facilitating vessel remodeling. Our study provides the first evidence that
      ROS play a fundamental role in flow-induced vascular enlargement.

PMID- 16109922
TI  - Obesity and endothelial function.

PMID- 16109923
TI  - Endothelial progenitor cells: unexpected disclosures.

PMID- 16109924
TI  - Mitochondria and reactive oxygen species: an evolution in function.

PMID- 16109925
TI  - Associations between soluble CD40 ligand, atherosclerosis risk factors, and
      subclinical atherosclerosis: results from the Dallas Heart Study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the associations between
      plasma levels of soluble CD40 ligand (sCD40L), atherosclerosis risk factors, and
      evidence of subclinical atherosclerosis. METHODS AND RESULTS: Plasma levels of
      sCD40L were measured in 2811 subjects from the Dallas Heart Study, a multiethnic
      population-based cross-sectional study. Electron Beam Computed Tomography
      measurements of coronary artery calcium (CAC) and MRI measurements of aortic
      plaque were performed in 2198 and 1965 subjects, respectively. No association was
      observed between quartiles of sCD40L and age, sex, race, body mass index,
      diabetes, smoking, creatinine clearance, low-density lipoprotein cholesterol,
      high-density lipoprotein cholesterol, or C-reactive protein. In contrast, weak
      but statistically significant associations were observed between sCD40L and total
      cholesterol and triglycerides. The prevalence of detectable CAC (CAC score > or
      =10) and aortic plaque did not differ across sCD40L quartiles, and individuals
      with CAC scores <10, > or =10 to 100, >100 to 400, and >400 had similar sCD40L
      levels. CONCLUSIONS: In a large and representative multiethnic population-based
      sample, sCD40L was not associated with most atherosclerotic risk factors or with
      subclinical atherosclerosis. These findings suggest that sCD40L will not be
      useful as a tool to screen for the presence of subclinical atherosclerosis in the
      population. Further evaluation of this biomarker should focus on settings in
      which platelet activation is common, such as following acute coronary syndromes
      or coronary revascularization procedures.

PMID- 16109926
TI  - The yliA, -B, -C, and -D genes of Escherichia coli K-12 encode a novel
      glutathione importer with an ATP-binding cassette.
AB  - Glutathione protects cells and organisms from oxygen species and peroxides and is
      indispensable for aerobically living organisms. Moreover, it acts against
      xenobiotics and drugs by the formation and excretion of glutathione S conjugates.
      In this study, we show that the yliA, -B, -C, and -D genes of Escherichia coli K
      12 encode a glutathione transporter with the ATP-binding cassette. The
      transporter imports extracellular glutathione into the cytoplasm in an ATP
      dependent manner. This transporter, along with gamma-glutamyltranspeptidase, has
      an important role in E. coli growth with glutathione as a sole sulfur source.

PMID- 16109927
TI  - Characterization of the exosporium basal layer protein BxpB of Bacillus
      anthracis.
AB  - Bacillus anthracis spores, the cause of anthrax, are enclosed by a prominent
      loose-fitting structure called the exosporium. The exosporium is composed of a
      basal layer and an external hair-like nap. The filaments of the hair-like nap are
      apparently formed by a single collagen-like glycoprotein called BclA, whereas
      several different proteins form or are tightly associated with the basal layer.
      In this study, we used immunogold electron microscopy to demonstrate that BxpB
      (also called ExsF) is a component of the exosporium basal layer. Binding to the
      basal layer by an anti-BxpB monoclonal antibody was greatly increased by the loss
      of BclA. We found that BxpB and BclA are part of a stable complex that appears to
      include the putative basal layer protein ExsY and possibly other proteins.
      Previous results suggested that BxpB was glycosylated; however, our results
      indicate that it is not a glycoprotein. We showed that DeltabxpB spores, which
      lack BxpB, contain an exosporium devoid of hair-like nap even though the
      DeltabxpB strain produces normal levels of BclA. These results indicated that
      BxpB is required for the attachment of BclA to the exosporium. Finally, we found
      that the efficiency of production of DeltabxpB spores and their resistance
      properties were similar to those of wild-type spores. However, DeltabxpB spores
      germinate faster than wild-type spores, indicating that BxpB suppresses
      germination. This effect did not appear to be related to the absence from
      DeltabxpB spores of a hair-like nap or of enzymes that degrade germinants.

PMID- 16109928
TI  - The protein phosphatases of Synechocystis sp. strain PCC 6803: open reading
      frames sll1033 and sll1387 encode enzymes that exhibit both protein-serine and
      protein-tyrosine phosphatase activity in vitro.
AB  - The open reading frames (ORFs) encoding two potential protein-serine/threonine
      phosphatases from the cyanobacterium Synechocystis sp. strain PCC 6803 were
      cloned and their protein products expressed in Escherichia coli cells. The
      product of ORF sll1033, SynPPM3, is a homologue of the PPM family of protein
      serine/threonine phosphatases found in all eukaryotes as well as many members of
      the Bacteria. Surprisingly, the recombinant protein phosphatase dephosphorylated
      phosphotyrosine- as well as phosphoserine-containing proteins in vitro. While
      kinetic analyses indicate that the enzyme was more efficient at dephosphorylating
      the latter, replacement of Asp608 by asparagine enhanced activity toward a
      phosphotyrosine-containing protein fourfold. The product of ORF sll1387, SynPPP1,
      is the sole homolog of the PPP family of protein phosphatases encoded by the
      genome of Synechocystis sp. strain PCC 6803. Like many other bacterial PPPs, the
      enzyme dephosphorylated phosphoserine- and phosphotyrosine-containing proteins
      with comparable efficiencies. However, while previously described PPPs from
      prokaryotic organisms required the addition of exogenous metal ion cofactors,
      such as Mg2+ or Mn2+, for activity, recombinantly produced SynPPP1 displayed near
      maximal activity in the absence of added metals. Inductively coupled plasma mass
      spectrometry indicated that recombinant SynPPP1 contained significant quantities,
      0.32 to 0.44 mol/mole total, of Mg and Mn. In this respect, the cyanobacterial
      enzyme resembled eukaryotic members of the PPP family, which are metalloproteins.
      mRNA encoding SynPPP1 or SynPPM3 could be detected in cells grown under many, but
      not all, environmental conditions.

PMID- 16109929
TI  - Identification of genes of VSH-1, a prophage-like gene transfer agent of
      Brachyspira hyodysenteriae.
AB  - VSH-1 is a mitomycin C-inducible prophage of the anaerobic spirochete Brachyspira
      hyodysenteriae. Purified VSH-1 virions are noninfectious, contain random 7.5-kb
      fragments of the bacterial genome, and mediate generalized transduction of B.
      hyodysenteriae cells. In order to identify and sequence genes of this novel gene
      transfer agent (GTA), proteins associated either with VSH-1 capsids or with tails
      were purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The N
      terminal amino acid sequences of 11 proteins were determined. Degenerate PCR
      primers were designed from the amino acid sequences and used to amplify several
      VSH-1 genes from B. hyodysenteriae strain B204 DNA. A lambda clone library of B.
      hyodysenteriae B204 DNA was subsequently screened by Southern hybridization
      methods and used to identify and sequence overlapping DNA inserts containing
      additional VSH-1 genes. VSH-1 genes spanned 16.3 kb of the B. hyodysenteriae
      chromosome and were flanked by bacterial genes. VSH-1 identified genes and
      unidentified, intervening open reading frames were consecutively organized in
      head (seven genes), tail (seven genes), and lysis (four genes) clusters in the
      same transcriptional direction. Putative lysis genes encoding endolysin (Lys) and
      holin proteins were identified from sequence and structural similarities of their
      translated protein products with GenBank bacteriophage proteins. Recombinant Lys
      protein hydrolyzed peptidoglycan purified from B. hyodysenteriae cells. The
      identified VSH-1 genes exceed the DNA capacity of VSH-1 virions and do not encode
      traditional bacteriophage early functions involved in DNA replication. These
      genome properties explain the noninfectious nature of VSH-1 virions and further
      confirm its resemblance to known prophage-like, GTAs of other bacterial species,
      such as the GTA from Rhodobacter capsulatus. The identification of VSH-1 genes
      will enable analysis of the regulation of this GTA and should facilitate
      investigations of VSH-1-like prophages from other Brachyspira species.

PMID- 16109930
TI  - A LysR-type regulator, CidR, is required for induction of the Staphylococcus
      aureus cidABC operon.
AB  - The Staphylococcus aureus cidABC and lrgAB operons have been shown to regulate
      murein hydrolase activity and affect antibiotic tolerance. The cid operon
      enhances murein hydrolase activity and antibiotic sensitivity, whereas the lrg
      operon inhibits these processes. Based on these findings and the structural
      similarities of the cidA and lrgA gene products to the bacteriophage holin family
      of proteins, we have proposed that the cid and lrg operons encode holin- and
      antiholin-like proteins, respectively, that function to control the murein
      hydrolase activity produced by the bacteria. Analysis of cid operon transcription
      revealed the presence of two transcripts, one spanning all three cid genes and
      whose expression is induced by growth in the presence of acetic acid and the
      other spanning cidB and cidC only that is produced in a sigma B-dependent manner.
      The cidABC operon lies immediately downstream from the cidR gene, encoding a
      potential LysR-type transcriptional regulator. In this study, we demonstrate that
      cidR is involved in the regulation of cidABC expression. Northern blot analyses
      revealed that the cidR gene product positively regulates cidABC expression by
      increasing transcription in the presence of acetic acid produced as a result of
      the metabolism of glucose. As expected for an operon that encodes a positive
      effector of murein hydrolase activity, the upregulation of cidABC expression
      resulted in increased murein hydrolase activity produced by these cells.
      Furthermore, it was demonstrated that antibiotic tolerance and stationary-phase
      survival of S. aureus are affected by the cidR gene. Taken together, these
      results demonstrate that the cidR gene product functions as a transcriptional
      activator of cidABC transcription in response to acetic acid accumulation in the
      growth medium.

PMID- 16109931
TI  - ABC transporter for corrinoids in Halobacterium sp. strain NRC-1.
AB  - We report evidence for the existence of a putative ABC transporter for corrinoid
      utilization in the extremely halophilic archaeon Halobacterium sp. strain NRC-1.
      Results from genetic and nutritional analyses of Halobacterium showed that
      mutants with lesions in open reading frames (ORFs) Vng1370G, Vng1371Gm, and
      Vng1369G required a 10(5)-fold higher concentration of cobalamin for growth than
      the wild-type or parent strain. The data support the conclusion that these ORFs
      encode orthologs of the bacterial cobalamin ABC transporter permease (btuC;
      Vng1370G), ATPase (btuD; Vng1371Gm), and substrate-binding protein (btuF;
      Vng1369G) components. Mutations in the Vng1370G, Vng1371Gm, and Vng1369G genes
      were epistatic, consistent with the hypothesis that their products work together
      to accomplish the same function. Extracts of btuF mutant strains grown in the
      presence of cobalamin did not contain any cobalamin molecules detectable by a
      sensitive bioassay, whereas btuCD mutant strain extracts did. The data are
      consistent with the hypothesis that the BtuF protein is exported to the
      extracellular side of the cell membrane, where it can bind cobalamin in the
      absence of BtuC and BtuD. Our data also provide evidence for the regulation of
      corrinoid transport and biosynthesis. Halobacterium synthesized cobalamin in a
      chemically defined medium lacking corrinoid precursors. To the best of our
      knowledge, this is the first genetic analysis of an archaeal corrinoid transport
      system.

PMID- 16109932
TI  - A novel beta-peptidyl aminopeptidase (BapA) from strain 3-2W4 cleaves peptide
      bonds of synthetic beta-tri- and beta-dipeptides.
AB  - A novel bacterial strain that was capable of growing on the beta-tripeptide H
      betahVal-betahAla-betahLeu-OH as the sole carbon and nitrogen source was isolated
      from an enrichment culture. On the basis of physiological characterization,
      partial 16S rRNA sequencing, and fatty acid analysis, strain 3-2W4 was identified
      as a member of the family Sphingomonadaceae. Growth on the beta-tripeptide and
      the beta-dipeptide H-betahAla-betahLeu-OH was observed, and emerging metabolites
      were characterized. Small amounts of a persisting metabolite, the N-acetylated
      beta-dipeptide, were identified in both media. According to dissolved organic
      carbon measurements, 74 to 80% of the available carbon was dissimilated. The beta
      peptide-degrading enzyme was purified from the crude cell extract of cells from
      strain 3-2W4 grown on complex medium. The enzyme was composed of two subunits,
      and the N-terminal sequences of both were determined. With this information, it
      was possible to identify the complete nucleotide sequence and to deduce the
      primary structure of the gene bapA. The gene encoded a beta-peptidyl
      aminopeptidase (BapA) of 402 amino acids that was synthesized as preprotein with
      a signal sequence of 29 amino acids. The enzyme was cleaved into two subunits
      (residues 30 to 278 and 279 to 402). It belonged to the N-terminal nucleophile
      (Ntn) hydrolase superfamily.

PMID- 16109933
TI  - Adaptation to disruption of the electron transfer pathway for Fe(III) reduction
      in Geobacter sulfurreducens.
AB  - Previous studies demonstrated that an outer membrane c-type cytochrome, OmcB, was
      involved in Fe(III) reduction in Geobacter sulfurreducens. An OmcB-deficient
      mutant was greatly impaired in its ability to reduce both soluble and insoluble
      Fe(III). Reintroducing omcB restored the capacity for Fe(III) reduction at a
      level proportional to the level of OmcB production. Here, we report that the OmcB
      deficient mutant gradually adapted to grow on soluble Fe(III) but not insoluble
      Fe(III). The adapted OmcB-deficient mutant reduced soluble Fe(III) at a rate
      comparable to that of the wild type, but the cell yield of the mutant was only
      ca. 60% of that of the wild type under steady-state culturing conditions.
      Analysis of proteins and transcript levels demonstrated that expression of
      several membrane-associated cytochromes was higher in the adapted mutant than in
      the wild type. Further comparison of transcript levels during steady-state growth
      on Fe(III) citrate with a whole-genome DNA microarray revealed a significant
      shift in gene expression in an apparent attempt to adapt metabolism to the
      impaired electron transport to Fe(III). These results demonstrate that, although
      there are many other membrane-bound c-type cytochromes in G. sulfurreducens,
      increased expression of these cytochromes cannot completely compensate for the
      loss of OmcB. The concept that outer membrane cytochromes are promiscuous
      reductases that are interchangeable in function appears to be incorrect.
      Furthermore, the results indicate that there may be different mechanisms for
      electron transfer to soluble Fe(III) and insoluble Fe(III) oxides in G.
      sulfurreducens, which emphasizes the importance of studying electron transport to
      the environmentally relevant Fe(III) oxides.

PMID- 16109934
TI  - A phylogeny of bacterial RNA nucleotidyltransferases: Bacillus halodurans
      contains two tRNA nucleotidyltransferases.
AB  - We have analyzed the distribution of RNA nucleotidyltransferases from the family
      that includes poly(A) polymerases (PAP) and tRNA nucleotidyltransferases (TNT) in
      43 bacterial species. Genes of several bacterial species encode only one member
      of the nucleotidyltransferase superfamily (NTSF), and if that protein functions
      as a TNT, those organisms may not contain a poly(A) polymerase I like that of
      Escherichia coli. The genomes of several of the species examined encode more than
      one member of the nucleotidyltransferase superfamily. The function of some of
      those proteins is known, but in most cases no biochemical activity has been
      assigned to the NTSF. The NTSF protein sequences were used to construct an
      unrooted phylogenetic tree. To learn more about the function of the NTSFs in
      species whose genomes encode more than one, we have examined Bacillus halodurans.
      We have demonstrated that B. halodurans adds poly(A) tails to the 3' ends of RNAs
      in vivo. We have shown that the genes for both of the NTSFs encoded by the B.
      halodurans genome are transcribed in vivo. We have cloned, overexpressed, and
      purified the two NTSFs and have shown that neither functions as poly(A)
      polymerase in vitro. Rather, the two proteins function as tRNA
      nucleotidyltransferases, and our data suggest that, like some of the deep
      branching bacterial species previously studied by others, B. halodurans possesses
      separate CC- and A-adding tRNA nucleotidyltransferases. These observations raise
      the interesting question of the identity of the enzyme responsible for RNA
      polyadenylation in Bacillus.

PMID- 16109935
TI  - Proteomic analysis reveals the participation of energy- and stress-related
      proteins in the response of Pseudomonas putida DOT-T1E to toluene.
AB  - Pseudomonas putida DOT-T1E is tolerant to toluene and other toxic hydrocarbons
      through extrusion of the toxic compounds from the cell by means of three efflux
      pumps, TtgABC, TtgDEF, and TtgGHI. To identify other cellular factors that allow
      the growth of P. putida DOT-T1E in the presence of high concentrations of
      toluene, we performed two-dimensional gel analyses of proteins extracted from
      cultures grown on glucose in the presence and in the absence of the organic
      solvent. From a total of 531 spots, 134 proteins were observed to be toluene
      specific. In the absence of toluene, 525 spots were clearly separated and 117
      proteins were only present in this condition. Moreover, 35 proteins were induced
      by at least twofold in the presence of toluene whereas 26 were repressed by at
      least twofold under these conditions. We reasoned that proteins that were highly
      induced could play a role in toluene tolerance. These proteins, identified by
      matrix-assisted laser desorption ionization-time of flight mass spectrometry,
      were classified into four categories: 1, proteins involved in the catabolism of
      toluene; 2, proteins involved in the channeling of metabolic intermediates to the
      Krebs cycle and activation of purine biosynthesis; 3, proteins involved in sugar
      transport; 4, stress-related proteins. The set of proteins in groups 2 and 3
      suggests that the high energy demand required for solvent tolerance is achieved
      via activation of cell metabolism. The role of chaperones that facilitate the
      proper folding of newly synthesized proteins under toluene stress conditions was
      analyzed in further detail. Knockout mutants revealed that CspA, XenA, and Tuf-1
      play a role in solvent tolerance in Pseudomonas, although this role is probably
      not specific to toluene, as indicated by the fact that all mutants grew more
      slowly than the wild type without toluene.

PMID- 16109936
TI  - Transcriptional termination control of a novel ABC transporter gene involved in
      antibiotic resistance in Bacillus subtilis.
AB  - In members of one of the subfamilies of the bacterial ATP binding cassette (ABC)
      transporters, the two nucleotide binding domains are fused as a single peptide
      and the proteins have no membrane-spanning domain partners. Most of the ABC
      efflux transporters of this subfamily have been characterized in actinomycetes,
      producing macrolide, lincosamide, and streptogramin antibiotics. Among 40 ABC
      efflux transporters of Bacillus subtilis, five proteins belong to this subfamily.
      None of these proteins has been functionally characterized. We examined
      macrolide, lincosamide, and streptogramin antibiotic resistance in insertional
      disruptants of the genes that encode these proteins. It was found that only a
      disruptant of vmlR (formerly named expZ) showed hypersensitivity to virginiamycin
      M and lincomycin. Expression of the vmlR gene was induced by the addition of
      these antibiotics in growth medium. Primer extension analysis revealed that
      transcription of the vmlR gene initiates at an adenosine residue located 225 bp
      upstream of the initiation codon. From the analysis of the vmlR and lacZ fusion
      genes, a 52-bp deletion from +159 to +211 resulted in constitutive expression of
      the vmlR gene. In this region, a typical rho-independent transcriptional
      terminator was found. It was suggested that the majority of transcription ends at
      this termination signal in the absence of antibiotics, whereas under induced
      conditions, RNA polymerase reads through the terminator, and transcription
      continues to the downstream vmlR coding region, resulting in an increase in vmlR
      expression. No stabilization of vmlR mRNA occurred under the induced conditions.

PMID- 16109937
TI  - Identification of residues responsible for the defective virulence gene regulator
      Mga produced by a natural mutant of Streptococcus pyogenes.
AB  - Mga is a transcriptional regulator in the pathogen Streptococcus pyogenes that
      positively activates several important virulence genes involved in colonization
      and immune evasion in the human host. A naturally occurring mutant of Mga that is
      defective in its ability to activate transcription has been identified in the
      serotype M50 strain B514-Sm. Sequence alignment of the defective M50 Mga with the
      fully functional Mga from serotypes M4 and M49 revealed only three amino acid
      changes that might result in a defective protein. Electrophoretic mobility shift
      assays using purified M50 and M4 maltose binding protein-Mga found that both
      exhibited DNA-binding activity towards regulated promoters. Thus, the
      significance of each residue for the functionality of M50 Mga was explored
      through introduction of "gain-of-function" mutations based on M4 Mga.
      Transcriptional studies of the mutant alleles under both constitutive (PrpsL) and
      autoactivated (Pmga4) promoters illustrated that an arginine-to-methionine change
      at position 461 of M50 Mga protein fully restored activation of downstream genes.
      Western blot analyses of steady-state Mga levels suggest that the M461 residue
      may play a role in overall conformation and protein stability of Mga. However,
      despite the conservation of the M461 protein among all other Mga proteins, it
      does not appear to be necessary for activity in a divergent M6 Mga. These studies
      highlight the potential differences that exist between divergent Mga proteins in
      this important human pathogen.

PMID- 16109938
TI  - The heat shock genes dnaK, dnaJ, and grpE are involved in regulation of
      putisolvin biosynthesis in Pseudomonas putida PCL1445.
AB  - Pseudomonas putida PCL1445 produces two cyclic lipopeptides, putisolvins I and
      II, which possess surfactant activity and play an important role in biofilm
      formation and degradation. In order to identify genes and traits that are
      involved in the regulation of putisolvin production of PCL1445, a Tn5luxAB
      library was generated and mutants were selected for the lack of biosurfactant
      production using a drop-collapsing assay. Sequence analysis of the Tn5luxAB
      flanking region of one biosurfactant mutant, strain PCL1627, showed that the
      transposon had inserted in a dnaK homologue which is located downstream of grpE
      and upstream of dnaJ. Analysis of putisolvin production and expression studies
      indicate that dnaK, together with the dnaJ and grpE heat shock genes, takes part
      in the positive regulation (directly or indirectly) of putisolvin biosynthesis at
      the transcriptional level. Growth of PCL1445 at low temperature resulted in an
      increased level of putisolvins, and mutant analyses showed that this requires
      dnaK and dnaJ but not grpE. In addition, putisolvin biosynthesis of PCL1445 was
      found to be dependent on the GacA/GacS two-component signaling system. Expression
      analysis indicated that dnaK is positively regulated by GacA/GacS.

PMID- 16109939
TI  - Species and incompatibility determination within the P1par family of plasmid
      partition elements.
AB  - The P1par family of active plasmid partition systems consists of at least six
      members, broadly distributed in a variety of plasmid types and bacterial genera.
      Each encodes two Par proteins and contains a cis-acting parS site. Individual par
      systems can show distinct species specificities; the proteins from one type
      cannot function with the parS site of another. P1par-versus-P7par specificity
      resides within two hexamer BoxB repeats encoded by parS that contact the ParB
      protein near the carboxy terminus. Here, we examine the species specificity
      differences between Yersinia pestis pMT1parS and Escherichia coli P1 and P7parS.
      pMT1parS site specificity could be altered to that of either P1 or P7 by point
      mutation changes in the BoxB repeats. Just one base change in a single BoxB
      repeat sometimes sufficed. The BoxB sequence appears to be able to adopt a number
      of forms that define exclusive interactions with different ParB species. The
      looped parS structure may facilitate this repertoire of interaction
      specificities. Different P1par family members have different partition-mediated
      incompatibility specificities. This property defines whether two related plasmids
      can coexist in the same cell and is important in promoting the evolution of new
      plasmid species. BoxB sequence changes that switch species specificity between
      P1, P7, and pMT1 species switched partition-mediated plasmid incompatibility in
      concert. Thus, there is a direct mechanistic link between species specificity and
      partition-mediated incompatibility, and the BoxB-ParB interaction can be regarded
      as a special mechanism for facilitating plasmid evolution.

PMID- 16109940
TI  - Induction of manganese-containing superoxide dismutase is required for acid
      tolerance in Vibrio vulnificus.
AB  - The manganese-containing superoxide dismutase (MnSOD) of Vibrio vulnificus,
      normally detected after the onset of the stationary phase, is expressed during
      the lag that immediately follows the transfer of cells grown exponentially to a
      fresh medium acidified to pH 5.0, whereas Fe-containing SOD is constitutively
      expressed. The signal triggering the growth lag and MnSOD induction therein is
      not low pH but intracellular superoxide accumulated under these conditions, since
      addition of a superoxide scavenger not only shortened the lag but also abrogated
      the MnSOD induction. If the lysine decarboxylase reaction proceeds in the
      presence of sufficient lysine, the broth is rapidly neutralized to abolish the
      generation of oxidative stress. Accordingly, the acid tolerance response was
      examined without the addition of lysine. SoxR regulates MnSOD induction. Lack of
      MnSOD caused by mutations in soxR or sodA resulted in low tolerance to low pH.
      The fur mutant derepressing MnSOD showed better tolerance than the wild type.
      Thus, an increase in total cytosolic SOD activity through MnSOD induction is
      essential for the cell to withstand the acid challenge. The contribution of
      cuprozinc-containing SOD to acid tolerance is not significant compared with those
      of cytosolic SODs.

PMID- 16109941
TI  - Cytochrome c maturation and the physiological role of c-type cytochromes in
      Vibrio cholerae.
AB  - Vibrio cholerae lives in different habitats, varying from aquatic ecosystems to
      the human intestinal tract. The organism has acquired a set of electron transport
      pathways for aerobic and anaerobic respiration that enable adaptation to the
      various environmental conditions. We have inactivated the V. cholerae ccmE gene,
      which is required for cytochrome c biogenesis. The resulting strain is deficient
      of all c-type cytochromes and allows us to characterize the physiological role of
      these proteins. Under aerobic conditions in rich medium, V. cholerae produces at
      least six c-type cytochromes, none of which is required for growth. Wild-type V.
      cholerae produces active fumarate reductase, trimethylamine N-oxide reductase,
      cbb3 oxidase, and nitrate reductase, of which only the fumarate reductase does
      not require maturation of c-type cytochromes. The reduction of nitrate in the
      medium resulted in the accumulation of nitrite, which is toxic for the cells.
      This suggests that V. cholerae is able to scavenge nitrate from the environment
      only in the presence of other nitrite-reducing organisms. The phenotypes of
      cytochrome c-deficient V. cholerae were used in a transposon mutagenesis
      screening to search for additional genes required for cytochrome c maturation.
      Over 55,000 mutants were analyzed for nitrate reductase and cbb3 oxidase
      activity. No transposon insertions other than those within the ccm genes for
      cytochrome c maturation and the dsbD gene, which encodes a disulphide bond
      reductase, were found. In addition, the role of a novel CcdA-like protein in cbb3
      oxidase assembly is discussed.

PMID- 16109942
TI  - E1 enzyme of the pyruvate dehydrogenase complex in Corynebacterium glutamicum:
      molecular analysis of the gene and phylogenetic aspects.
AB  - The E1p enzyme is an essential part of the pyruvate dehydrogenase complex (PDHC)
      and catalyzes the oxidative decarboxylation of pyruvate with concomitant
      acetylation of the E2p enzyme within the complex. We analyzed the Corynebacterium
      glutamicum aceE gene, encoding the E1p enzyme, and constructed and characterized
      an E1p-deficient mutant. Sequence analysis of the C. glutamicum aceE gene and
      adjacent regions revealed that aceE is not flanked by genes encoding other
      enzymes of the PDHC. Transcriptional analysis revealed that aceE from C.
      glutamicum is monocistronic and that its transcription is initiated 121
      nucleotides upstream of the translational start site. Inactivation of the
      chromosomal aceE gene led to the inability to grow on glucose and to the absence
      of PDHC and E1p activities, indicating that only a single E1p enzyme is present
      in C. glutamicum and that the PDHC is essential for the growth of this organism
      on carbohydrate substrates. Surprisingly, the E1p enzyme of C. glutamicum showed
      up to 51% identity to homodimeric E1p proteins from gram-negative bacteria but no
      similarity to E1 alpha- or beta-subunits of heterotetrameric E1p enzymes which
      are generally assumed to be typical for gram-positives. To investigate the
      distribution of E1p enzymes in bacteria, we compiled and analyzed the phylogeny
      of 46 homodimeric E1p proteins and of 58 alpha-subunits of heterotetrameric E1p
      proteins deposited in public databases. The results revealed that the
      distribution of homodimeric and heterotetrameric E1p subunits in bacteria is not
      in accordance with the rRNA-based phylogeny of bacteria and is more heterogeneous
      than previously assumed.

PMID- 16109943
TI  - Regulation of the Bacillus subtilis ytmI operon, involved in sulfur metabolism.
AB  - The YtlI regulator of Bacillus subtilis activates the transcription of the ytmI
      operon encoding an l-cystine ABC transporter, a riboflavin kinase, and proteins
      of unknown function. The expression of the ytlI gene and the ytmI operon was high
      with methionine and reduced with sulfate. Using deletions and site-directed
      mutagenesis, a cis-acting DNA sequence important for YtlI-dependent regulation
      was identified upstream from the -35 box of ytmI. Gel mobility shift assays
      confirmed that YtlI specifically interacted with this sequence. The replacement
      of the sulfur-regulated ytlI promoter by the xylA promoter led to constitutive
      expression of a ytmI'-lacZ fusion in a ytlI mutant, suggesting that the
      repression of ytmI expression by sulfate was mainly at the level of YtlI
      synthesis. We further showed that the YrzC regulator negatively controlled ytlI
      expression while this repressor also acted on ytmI expression via YtlI. The
      cascade of regulation observed in B. subtilis is conserved in Listeria spp. Both
      a YtlI-like regulator and a ytmI-type operon are present in Listeria spp. Indeed,
      the Lmo2352 protein from Listeria monocytogenes was able to replace YtlI for the
      activation of ytmI expression and a lmo2352'-lacZ fusion was repressed in the
      presence of sulfate via YrzC in B. subtilis. A common motif, AT(A/T)ATTCCTAT, was
      found in the promoter region of the ytlI and lmo2352 genes. Deletion of part of
      this motif or the introduction of point mutations in this sequence confirmed its
      involvement in ytlI regulation.

PMID- 16109944
TI  - Heterocyst-specific excision of the Anabaena sp. strain PCC 7120 hupL element
      requires xisC.
AB  - In nitrogen-limiting conditions, approximately 10% of the vegetative cells in
      filaments of the cyanobacterium Anabaena (Nostoc) sp. strain PCC 7120
      differentiate into nitrogen-fixing heterocysts. During the late stages of
      heterocyst differentiation, three DNA elements, each embedded within an open
      reading frame, are programmed to excise from the chromosome by site-specific
      recombination. The DNA elements are named after the genes that they interrupt:
      nifD, fdxN, and hupL. The nifD and fdxN elements each contain a gene, xisA or
      xisF, respectively, that encodes the site-specific recombinase required for
      programmed excision of the element. Here, we show that the xisC gene (alr0677),
      which is present at one end of the 9,435-bp hupL element, is required for
      excision of the hupL element. A strain in which the xisC gene was inactivated
      showed no detectable excision of the hupL element. hupL encodes the large subunit
      of uptake hydrogenase. The xisC mutant forms heterocysts and grows
      diazotrophically, but unlike the wild type, it evolved hydrogen gas under
      nitrogen-fixing conditions. Overexpression of xisC from a plasmid in a wild-type
      background caused a low level of hupL rearrangement even in nitrogen-replete
      conditions. Expression of xisC in Escherichia coli was sufficient to produce
      rearrangement of an artificial substrate plasmid bearing the hupL element
      recombination sites. Sequence analysis indicated that XisC is a divergent member
      of the phage integrase family of recombinases. Site-directed mutagenesis of xisC
      showed that the XisC recombinase has functional similarity to the phage integrase
      family.

PMID- 16109945
TI  - Phosphoenolpyruvate carboxykinase is an acid-induced, chromosomally encoded
      virulence factor in Agrobacterium tumefaciens.
AB  - The pckA gene, encoding phosphoenolpyruvate carboxykinase, catalyzes the
      reversible decarboxylation and phosphorylation of oxaloacetate to form
      phosphoenolpyruvate. Located on the circular chromosome of Agrobacterium, this
      locus is adjacent to the loci chvG and chvI, encoding a two-component regulatory
      system that has been shown to be important in virulence. Using a reporter gene
      fusion, studies showed that the pckA gene is induced by acidic pH but not by
      acetosyringone. This acid induction is regulated by the chvG-chvI regulatory
      system, which controls acid-inducible genes. A pckA mutant had no demonstrable
      PckA enzyme activity and grew on AB minimal medium with glucose but did not grow
      on the same medium with succinate as the sole carbon source and was more
      inhibited in its growth than the wild-type strain by an acidic environment. A
      pckA mutant was highly attenuated in tumor-inducing ability on tobacco leaf disks
      and was severely attenuated in vir gene expression. Although vir gene induction
      was completely restored when a constitutive virG gene was introduced into the
      mutant strain, virulence was only partially restored. These results suggest that
      avirulence may be due to a combination of the inhibition of this mutant in the
      acidic plant wound environment and the poor induction of the vir genes.

PMID- 16109946
TI  - Heat shock response of Archaeoglobus fulgidus.
AB  - The heat shock response of the hyperthermophilic archaeon Archaeoglobus fulgidus
      strain VC-16 was studied using whole-genome microarrays. On the basis of the
      resulting expression profiles, approximately 350 of the 2,410 open reading frames
      (ORFs) (ca. 14%) exhibited increased or decreased transcript abundance. These
      span a range of cell functions, including energy production, amino acid
      metabolism, and signal transduction, where the majority are uncharacterized. One
      ORF called AF1298 was identified that contains a putative helix-turn-helix DNA
      binding motif. The gene product, HSR1, was expressed and purified from
      Escherichia coli and was used to characterize specific DNA recognition regions
      upstream of two A. fulgidus genes, AF1298 and AF1971. The results indicate that
      AF1298 is autoregulated and is part of an operon with two downstream genes that
      encode a small heat shock protein, Hsp20, and cdc48, an AAA+ ATPase. The DNase I
      footprints using HSR1 suggest the presence of a cis-binding motif upstream of
      AF1298 consisting of CTAAC-N5-GTTAG. Since AF1298 is negatively regulated in
      response to heat shock and encodes a protein only distantly related to the N
      terminal DNA binding domain of Phr of Pyrococcus furiosus, these results suggest
      that HSR1 and Phr may belong to an evolutionarily diverse protein family involved
      in heat shock regulation in hyperthermophilic and mesophilic Archaea organisms.

PMID- 16109947
TI  - PtrB of Pseudomonas aeruginosa suppresses the type III secretion system under the
      stress of DNA damage.
AB  - In a search for regulatory genes of the type III secretion system (TTSS) in
      Pseudomonas aeruginosa, transposon (Tn5) insertional mutants of the prtR gene
      were found defective in the TTSS. PrtR is an inhibitor of prtN, which encodes a
      transcriptional activator for pyocin synthesis genes. In P. aeruginosa, pyocin
      synthesis is activated when PrtR is degraded during the SOS response. Treatment
      of a wild-type P. aeruginosa strain with mitomycin C, a DNA-damaging agent,
      resulted in the inhibition of TTSS activation. A prtR/prtN double mutant had the
      same TTSS defect as the prtR mutant, and complementation by a prtR gene but not
      by a prtN gene restored the TTSS function. Also, overexpression of the prtN gene
      in wild-type PAK had no effect on the TTSS; thus, PrtN is not involved in the
      repression of the TTSS. To identify the PrtR-regulated TTSS repressor, another
      round of Tn mutagenesis was carried out in the background of a prtR/prtN double
      mutant. Insertion in a small gene, designated ptrB, restored the normal TTSS
      activity. Expression of ptrB is specifically repressed by PrtR, and mitomycin C
      mediated suppression of the TTSS is also abolished in a ptrB mutant strain.
      Therefore, PtrB is a new TTSS repressor that coordinates TTSS repression and
      pyocin synthesis under the stress of DNA damage.

PMID- 16109948
TI  - MtdC, a novel class of methylene tetrahydromethanopterin dehydrogenases.
AB  - Novel methylene tetrahydromethanopterin (H4MPT) dehydrogenase enzymes, named
      MtdC, were purified after expressing in Escherichia coli genes from,
      respectively, Gemmata sp. strain Wa1-1 and environmental DNA originating from
      unidentified microbial species. The MtdC enzymes were shown to possess high
      affinities for methylene-H4MPT and NADP but low affinities for methylene
      tetrahydrofolate or NAD. The substrate range and the kinetic properties revealed
      by MtdC enzymes distinguish them from the previously characterized bacterial
      methylene-H4MPT dehydrogenases, MtdA and MtdB. While revealing higher sequence
      similarity to MtdA enzymes, MtdC enzymes appear to fulfill a function homologous
      to the function of MtdB, as part of the H4MPT-linked pathway for formaldehyde
      oxidation/detoxification.

PMID- 16109949
TI  - An amino-terminal secretion signal is required for YplA export by the Ysa, Ysc,
      and flagellar type III secretion systems of Yersinia enterocolitica biovar 1B.
AB  - Yersinia enterocolitica biovar 1B maintains three distinct type III secretion
      (TTS) systems, which independently operate to target proteins to extracellular
      sites. The Ysa and Ysc systems are prototypical contact-dependent TTS systems
      that translocate toxic effectors to the cytosols of targeted eukaryotic host
      cells during infection. The flagellar TTS system is utilized during the assembly
      of the flagellum and is required for secretion of the virulence-associated
      phospholipase YplA to the bacterial milieu. When ectopically produced, YplA is
      also a secretion substrate for the Ysa and Ysc TTS systems. In this study, we
      define elements that allow YplA recognition and export by the Ysa, Ysc, and
      flagellar TTS systems. Fusion of various amino-terminal regions of YplA to
      Escherichia coli alkaline phosphatase (PhoA) lacking its native secretion signal
      demonstrated that the first 20 amino acids or corresponding mRNA codons of YplA
      were sufficient for export of YplA-PhoA chimeras by each TTS system. Export of
      native YplA by each of the three TTS systems was also found to depend on the
      integrity of its amino terminus. Introduction of a frameshift mutation or
      deletion of yplA sequences encoding the amino-terminal 20 residues negatively
      impacted YplA secretion. Deletion of other yplA regions was tolerated, including
      that resulting in the removal of amino acid residues 30 through 40 of the
      polypeptide and removal of the 5' untranslated region of the mRNA. This work
      supports a model in which independent and distantly related TTS systems of Y.
      enterocolitica recognize protein substrates by a similar mechanism.

PMID- 16109950
TI  - Gene organization and transcriptional analysis of the tprJ, tprI, tprG, and tprF
      loci in Treponema pallidum strains Nichols and Sea 81-4.
AB  - The tpr gene family of Treponema pallidum subsp. pallidum, the causative agent of
      syphilis, has recently become the focus of intensive investigation. TprF and TprI
      sequences are highly conserved among different isolates and are the targets of
      strong humoral and cellular immune responses of the host, and immunization with a
      recombinant peptide from the amino terminus of these antigens has been shown to
      alter significantly lesion development following homologous challenge. This
      indicates that these antigens are expressed during infection and strongly
      suggests a key functionality. tprF and tprI are located immediately downstream of
      the tprG and tprJ genes, respectively, separated by very short intergenic spacers
      (55 nucleotides for G-F and 56 nucleotides for J-I). Preliminary analysis using
      gene-specific primers failed to amplify tprJ in the Sea 81-4 isolate. In this
      study, sequence and transcriptional analysis of these loci showed a similar gene
      organization in the Nichols and Sea 81-4 strains, a complex pattern of
      transcription, and the presence of G homopolymeric repeats of variable lengths
      upstream of the tprF, tprI, tprG, and tprJ transcriptional start sites. However,
      distinctive features were also identified in the Sea 81-4 isolate, including a
      tprG-like open reading frame in the tprJ locus, a frameshift and a premature
      termination in the tprG coding sequence, a longer tprG-tprF intergenic spacer,
      and absence of cotranscription of the tprG-tprF genes.

PMID- 16109951
TI  - The toxin-antitoxin system of the streptococcal plasmid pSM19035.
AB  - pSM19035 of the pathogenic bacterium Streptococcus pyogenes is a low-copy-number
      plasmid carrying erythromycin resistance, stably maintained in a broad range of
      gram-positive bacteria. We show here that the omega-epsilon-zeta operon of this
      plasmid constitutes a novel proteic plasmid addiction system in which the epsilon
      and zeta genes encode an antitoxin and toxin, respectively, while omega plays an
      autoregulatory function. Expression of toxin Zeta is bactericidal for the gram
      positive Bacillus subtilis and bacteriostatic for the gram-negative Escherichia
      coli. The toxic effects of zeta gene expression in both bacterial species are
      counteracted by proper expression of epsilon. The epsilon-zeta toxin-antitoxin
      cassette stabilizes plasmids in E. coli less efficiently than in B. subtilis.

PMID- 16109952
TI  - Discordant 16S and 23S rRNA gene phylogenies for the genus Helicobacter:
      implications for phylogenetic inference and systematics.
AB  - Analysis of 16S rRNA gene sequences has become the primary method for determining
      prokaryotic phylogeny. Phylogeny is currently the basis for prokaryotic
      systematics. Therefore, the validity of 16S rRNA gene-based phylogenetic analyses
      is of fundamental importance for prokaryotic systematics. Discrepancies between
      16S rRNA gene analyses and DNA-DNA hybridization and phenotypic analyses have
      been noted in the genus Helicobacter. To clarify these discrepancies, we
      sequenced the 23S rRNA genes for 55 helicobacter strains representing 41 taxa
      (>2,700 bases per sequence). Phylogenetic-tree construction using neighbor
      joining, parsimony, and maximum likelihood methods for 23S rRNA gene sequence
      data yielded stable trees which were consistent with other phenotypic and
      genotypic methods. The 16S rRNA gene sequence-derived trees were discordant with
      the 23S rRNA gene trees and other data. Discrepant 16S rRNA gene sequence data
      for the helicobacters are consistent with the horizontal transfer of 16S rRNA
      gene fragments and the creation of mosaic molecules with loss of phylogenetic
      information. These results suggest that taxonomic decisions must be supported by
      other phylogenetically informative macromolecules, such as the 23S rRNA gene,
      when 16S rRNA gene-derived phylogeny is discordant with other credible phenotypic
      and genotypic methods. This study found Wolinella succinogenes to branch with the
      unsheathed-flagellum cluster of helicobacters by 23S rRNA gene analyses and whole
      genome comparisons. This study also found intervening sequences (IVSs) in the 23S
      rRNA genes of strains of 12 Helicobacter species. IVSs were found in helices 10,
      25, and 45, as well as between helices 31' and 27'. Simultaneous insertion of
      IVSs at three sites was found in H. mesocricetorum.

PMID- 16109953
TI  - Exploring Lactobacillus plantarum genome diversity by using microarrays.
AB  - Lactobacillus plantarum is a versatile and flexible species that is encountered
      in a variety of niches and can utilize a broad range of fermentable carbon
      sources. To assess if this versatility is linked to a variable gene pool,
      microarrays containing a subset of small genomic fragments of L. plantarum strain
      WCFS1 were used to perform stringent genotyping of 20 strains of L. plantarum
      from various sources. The gene categories with the most genes conserved in all
      strains were those involved in biosynthesis or degradation of structural
      compounds like proteins, lipids, and DNA. Conversely, genes involved in sugar
      transport and catabolism were highly variable between strains. Moreover, besides
      the obvious regions of variance, like prophages, other regions varied between the
      strains, including regions encoding plantaricin biosynthesis, nonribosomal
      peptide biosynthesis, and exopolysaccharide biosynthesis. In many cases, these
      variable regions colocalized with regions of unusual base composition. Two large
      regions of flexibility were identified between 2.70 and 2.85 and 3.10 and 3.29 Mb
      of the WCFS1 chromosome, the latter being close to the origin of replication. The
      majority of genes encoded in these variable regions are involved in sugar
      metabolism. This functional overrepresentation and the unusual base composition
      of these regions led to the hypothesis that they represented lifestyle adaptation
      regions in L. plantarum. The present study consolidates this hypothesis by
      showing that there is a high degree of gene content variation among L. plantarum
      strains in genes located in these regions of the WCFS1 genome. Interestingly,
      based on our genotyping data L. plantarum strains clustered into two clearly
      distinguishable groups, which coincided with an earlier proposed subdivision of
      this species based on conventional methods.

PMID- 16109954
TI  - Biodiversity-based identification and functional characterization of the mannose
      specific adhesin of Lactobacillus plantarum.
AB  - Lactobacillus plantarum is a frequently encountered inhabitant of the human
      intestinal tract, and some strains are marketed as probiotics. Their ability to
      adhere to mannose residues is a potentially interesting characteristic with
      regard to proposed probiotic features such as colonization of the intestinal
      surface and competitive exclusion of pathogens. In this study, the variable
      capacity of 14 L. plantarum strains to agglutinate Saccharomyces cerevisiae in a
      mannose-specific manner was determined and subsequently correlated with an L.
      plantarum WCFS1-based genome-wide genotype database. This led to the
      identification of four candidate mannose adhesin-encoding genes. Two genes
      primarily predicted to code for sortase-dependent cell surface proteins displayed
      a complete gene-trait match. Their involvement in mannose adhesion was
      corroborated by the finding that a sortase (srtA) mutant of L. plantarum WCFS1
      lost the capacity to agglutinate S. cerevisiae. The postulated role of these two
      candidate genes was investigated by gene-specific deletion and overexpression in
      L. plantarum WCFS1. Subsequent evaluation of the mannose adhesion capacity of the
      resulting mutant strains showed that inactivation of one candidate gene (lp_0373)
      did not affect mannose adhesion properties. In contrast, deletion of the other
      gene (lp_1229) resulted in a complete loss of yeast agglutination ability, while
      its overexpression quantitatively enhanced this phenotype. Therefore, this gene
      was designated to encode the mannose-specific adhesin (Msa; gene name, msa) of L.
      plantarum. Domain homology analysis of the predicted 1,000-residue Msa protein
      identified known carbohydrate-binding domains, further supporting its role as a
      mannose adhesin that is likely to be involved in the interaction of L. plantarum
      with its host in the intestinal tract.

PMID- 16109955
TI  - Identification of the Mycobacterium tuberculosis SUF machinery as the exclusive
      mycobacterial system of [Fe-S] cluster assembly: evidence for its implication in
      the pathogen's survival.
AB  - The worldwide recrudescence of tuberculosis and widespread antibiotic resistance
      have strengthened the need for the rapid development of new antituberculous drugs
      targeting essential functions of its etiologic agent, Mycobacterium tuberculosis.
      In our search for new targets, we found that the M. tuberculosis pps1 gene, which
      contains an intein coding sequence, belongs to a conserved locus of seven open
      reading frames. In silico analyses indicated that the mature Pps1 protein is
      orthologous to the SufB protein of many organisms, a highly conserved component
      of the [Fe-S] cluster assembly and repair SUF (mobilization of sulfur) machinery.
      We showed that the mycobacterial pps1 locus constitutes an operon which encodes
      Suf-like proteins. Interactions between these proteins were demonstrated,
      supporting the functionality of the M. tuberculosis SUF system. The noticeable
      absence of any alternative [Fe-S] cluster assembly systems in mycobacteria is in
      agreement with the apparent essentiality of the suf operon in Mycobacterium
      smegmatis. Altogether, these results establish that Pps1, as a central element of
      the SUF system, could play an essential function for M. tuberculosis survival
      virtually through its implication in the bacterial resistance to iron limitation
      and oxidative stress. As such, Pps1 may represent an interesting molecular target
      for new antituberculous drugs.

PMID- 16109956
TI  - Effects of nitrogen and carbon sources on transcription of soluble
      methyltransferases in Methanosarcina mazei strain Go1.
AB  - The methanogenic archaeon Methanosarcina mazei strain Go1 uses versatile carbon
      sources and is able to fix molecular nitrogen with methanol as carbon and energy
      sources. Here, we demonstrate that when growing on trimethylamine (TMA), nitrogen
      fixation does not occur, indicating that ammonium released during TMA degradation
      is sufficient to serve as a nitrogen source and represses nif gene induction. We
      further report on the transcriptional regulation of soluble methyltransferases,
      which catalyze the initial step of methylamine consumption by methanogenesis, in
      response to different carbon and nitrogen sources. Unexpectedly, we obtained
      conclusive evidence that transcription of the mtmB2C2 operon, encoding a
      monomethylamine (MMA) methyltransferase and its corresponding corrinoid protein,
      is highly increased under nitrogen limitation when methanol serves as a carbon
      source. In contrast, transcription of the homologous mtmB1C1 operon is not
      affected by the nitrogen source but appears to be increased when TMA is the sole
      carbon and energy source. In general, transcription of operons encoding
      dimethylamine (DMA) and TMA methyltransferases and methylcobalamine:coenzyme M
      methyltransferases is not regulated in response to the nitrogen source. However,
      in all cases transcription of one of the homologous operons or genes is increased
      by TMA or its degradation products DMA and MMA.

PMID- 16109957
TI  - Characterization of the genome composition of Bartonella koehlerae by microarray
      comparative genomic hybridization profiling.
AB  - Bartonella henselae is present in a wide range of wild and domestic feline hosts
      and causes cat-scratch disease and bacillary angiomatosis in humans. We have
      estimated here the gene content of Bartonella koehlerae, a novel species isolated
      from cats that was recently identified as an agent of human endocarditis. The
      investigation was accomplished by comparative genomic hybridization (CGH) to a
      microarray constructed from the sequenced 1.93-Mb genome of B. henselae. Control
      hybridizations of labeled DNA from the human pathogen Bartonella quintana with a
      reduced genome of 1.58 Mb were performed to evaluate the accuracy of the array
      for genes with known levels of sequence divergence. Genome size estimates of B.
      koehlerae by pulsed-field gel electrophoresis matched that calculated by the CGH,
      indicating a genome of 1.7 to 1.8 Mb with few unique genes. As in B. quintana,
      sequences in the prophage and the genomic islands were reported absent in B.
      koehlerae. In addition, sequence variability was recorded in the chromosome II
      like region, where B. koehlerae showed an intermediate retention pattern of both
      coding and noncoding sequences. Although most of the genes missing in B.
      koehlerae are also absent from B. quintana, its phylogenetic placement near B.
      henselae suggests independent deletion events, indicating that host specificity
      is not solely attributed to genes in the genomic islands. Rather, the results
      underscore the instability of the genomic islands even within bacterial
      populations adapted to the same host-vector system, as in the case of B. henselae
      and B. koehlerae.

PMID- 16109958
TI  - Immobilization of Escherichia coli RNA polymerase and location of binding sites
      by use of chromatin immunoprecipitation and microarrays.
AB  - The genome-wide location of RNA polymerase binding sites was determined in
      Escherichia coli using chromatin immunoprecipitation and microarrays (chIP-chip).
      Cross-linked chromatin was isolated in triplicate from rifampin-treated cells,
      and DNA bound to RNA polymerase was precipitated with an antibody specific for
      the beta' subunit. The DNA was amplified and hybridized to "tiled"
      oligonucleotide microarrays representing the whole genome at 25-bp resolution. A
      total of 1,139 binding sites were detected and evaluated by comparison to gene
      expression data from identical conditions and to 961 promoters previously
      identified by established methods. Of the detected binding sites, 418 were
      located within 1,000 bp of a known promoter, leaving 721 previously unknown RNA
      polymerase binding sites. Within 200 bp, we were able to detect 51% (189/368) of
      the known sigma70-specific promoters occurring upstream of an expressed open
      reading frame and 74% (273/368) within 1,000 bp. Conversely, many known promoters
      were not detected by chIP-chip, leading to an estimated 26% negative-detection
      rate. Most of the detected binding sites could be associated with expressed
      transcription units, but 299 binding sites occurred near inactive transcription
      units. This map of RNA polymerase binding sites represents a foundation for
      studies of transcription factors in E. coli and an important evaluation of the
      chIP-chip technique.

PMID- 16109959
TI  - Domain structure of HrpE, the Hrp pilus subunit of Xanthomonas campestris pv.
      vesicatoria.
AB  - The plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria possesses a
      type III secretion (TTS) system necessary for pathogenicity in susceptible hosts
      and induction of the hypersensitive response in resistant plants. This
      specialized protein transport system is encoded by a 23-kb hrp (hypersensitive
      response and pathogenicity) gene cluster. X. campestris pv. vesicatoria produces
      filamentous structures, Hrp pili, at the cell surface under hrp-inducing
      conditions. The Hrp pilus acts as a cell surface appendage of the TTS system and
      serves as a conduit for the transfer of bacterial effector proteins into the
      plant cell cytosol. The major pilus component, the HrpE pilin, is unique to
      xanthomonads and is encoded within the hrp gene cluster. In this study,
      functional domains of HrpE were mapped by linker-scanning mutagenesis and by
      reporter protein fusions to an N-terminally truncated avirulence protein
      (AvrBs3Delta2). Thirteen five-amino-acid peptide insertion mutants were obtained
      and could be grouped into six phenotypic classes. Three permissive mutations were
      mapped in the N-terminal half of HrpE, which is weakly conserved within the HrpE
      protein family. Four dominant-negative peptide insertions in the strongly
      conserved C-terminal region suggest that this domain is critical for
      oligomerization of the pilus subunits. Reporter protein fusions revealed that the
      N-terminal 17 amino acid residues act as an efficient TTS signal. From these
      results, we postulate a three-domain structure of HrpE with an N-terminal
      secretion signal, a surface-exposed variable region of the N-terminal half, and a
      C-terminal polymerization domain. Comparisons with a mutant study of HrpA, the
      Hrp pilin from Pseudomonas syringae pv. tomato DC3000, and hydrophobicity plot
      analyses of several nonhomologous Hrp pilins suggest a common architecture of Hrp
      pilins of different plant-pathogenic bacteria.

PMID- 16109961
TI  - The active site is the least stable structure in the unfolding pathway of a
      multidomain cold-adapted alpha-amylase.
AB  - The cold-active alpha-amylase from the Antarctic bacterium Pseudoalteromonas
      haloplanktis (AHA) is the largest known multidomain enzyme that displays
      reversible thermal unfolding (around 30 degrees C) according to a two-state
      mechanism. Transverse urea gradient gel electrophoresis (TUG-GE) from 0 to 6.64 M
      was performed under various conditions of temperature (3 degrees C to 70 degrees
      C) and pH (7.5 to 10.4) in the absence or presence of Ca2+ and/or Tris
      (competitive inhibitor) to identify possible low-stability domains. Contrary to
      previous observations by strict thermal unfolding, two transitions were found at
      low temperature (12 degrees C). Within the duration of the TUG-GE, the structures
      undergoing the first transition showed slow interconversions between different
      conformations. By comparing the properties of the native enzyme and the N12R
      mutant, the active site was shown to be part of the least stable structure in the
      enzyme. The stability data supported a model of cooperative unfolding of
      structures forming the active site and independent unfolding of the other more
      stable protein domains. In light of these findings for AHA, it will be valuable
      to determine if active-site instability is a general feature of heat-labile
      enzymes from psychrophiles. Interestingly, the enzyme was also found to refold
      and rapidly regain activity after being heated at 70 degrees C for 1 h in 6.5 M
      urea. The study has identified fundamental new properties of AHA and extended our
      understanding of structure/stability relationships of cold-adapted enzymes.

PMID- 16109960
TI  - Presence of multiple sites containing polar material in spherical Escherichia
      coli cells that lack MreB.
AB  - In rod-shaped bacteria, certain proteins are specifically localized to the cell
      poles. The nature of the positional information that leads to the proper
      localization of these proteins is unclear. In a screen for factors required for
      the localization of the Shigella sp. actin assembly protein IcsA to the bacterial
      pole, a mutant carrying a transposon insertion in mreB displayed altered
      targeting of IcsA. The phenotype of cells containing a transposon insertion in
      mreB was indistinguishable from that of cells containing a nonpolar mutation in
      mreB or that of wild-type cells treated with the MreB inhibitor A22. In cells
      lacking MreB, a green fluorescent protein (GFP) fusion to a cytoplasmic
      derivative of IcsA localized to multiple sites. Secreted full-length native IcsA
      was present in multiple faint patches on the surfaces of these cells in a pattern
      similar to that seen for the cytoplasmic IcsA-GFP fusion. EpsM, the polar Vibrio
      cholerae inner membrane protein, also localized to multiple sites in mreB cells
      and colocalized with IcsA, indicating that localization to multiple sites is not
      unique to IcsA. Our results are consistent with the requirement, either direct or
      indirect, for MreB in the restriction of certain polar material to defined sites
      within the cell and, in the absence of MreB, with the formation of ectopic sites
      containing polar material.

PMID- 16109962
TI  - Role of disulfide bridges in the activity and stability of a cold-active alpha
      amylase.
AB  - The cold-adapted alpha-amylase from Pseudoalteromonas haloplanktis unfolds
      reversibly and cooperatively according to a two-state mechanism at 30 degrees C
      and unfolds reversibly and sequentially with two transitions at temperatures
      below 12 degrees C. To examine the role of the four disulfide bridges in activity
      and conformational stability of the enzyme, the eight cysteine residues were
      reduced with beta-mercaptoethanol or chemically modified using iodoacetamide or
      iodoacetic acid. Matrix-assisted laser desorption-time of flight mass
      spectrometry analysis confirmed that all of the cysteines were modified. The
      iodoacetamide-modified enzyme reversibly folded/unfolded and retained
      approximately one-third of its activity. Removal of all disulfide bonds resulted
      in stabilization of the least stable region of the enzyme (including the active
      site), with a concomitant decrease in activity (increase in activation enthalpy).
      Disulfide bond removal had a greater impact on enzyme activity than on stability
      (particularly the active-site region). The functional role of the disulfide
      bridges appears to be to prevent the active site from developing ionic
      interactions. Overall, the study demonstrated that none of the four disulfide
      bonds are important in stabilizing the native structure of enzyme, and instead,
      they appear to promote a localized destabilization to preserve activity.

PMID- 16109963
TI  - The N-terminal domain of enterococcal surface protein, Esp, is sufficient for Esp
      mediated biofilm enhancement in Enterococcus faecalis.
AB  - Enterococci have emerged as one of the leading causes of nosocomial bloodstream,
      surgical site, and urinary tract infections. More recently, enterococci have been
      associated with biofilms, which are bacterial communities attached to a surface
      and encased in an extracellular polymeric matrix. The enterococcal cell surface
      associated protein, Esp, enhances biofilm formation by Enterococcus faecalis in a
      glucose-dependent manner. Mature Esp consists of a nonrepeat N-terminal domain
      and a central region made up of two types of tandem repeats followed by a C
      terminal membrane-spanning and anchor domain. This study was undertaken to
      localize the specific domain(s) of Esp that plays a role in Esp-mediated biofilm
      enhancement. To achieve this objective, we constructed in-frame deletion mutants
      expressing truncated forms of Esp in an isogenic background. By comparing strains
      expressing the mutant forms of Esp to those expressing wild-type Esp, we found
      that the strain expressing Esp lacking the N-terminal domain formed biofilms that
      were quantitatively less in biovolume than the strain expressing wild-type Esp.
      Furthermore, an E. faecalis strain expressing only the N-terminal domain of Esp
      fused to a heterologous protein anchor formed biofilms that were quantitatively
      similar to those formed by a strain expressing full-length Esp. This suggested
      that the minimal region contributing to Esp-mediated biofilm enhancement in E.
      faecalis was confined to the nonrepeat N-terminal domain. Expression of full
      length E. faecalis Esp in heterologous host systems of esp-deficient Lactococcus
      lactis and Enterococcus faecium did not enhance biofilm formation as was observed
      for E. faecalis. These results suggest that Esp may require interaction with an
      additional E. faecalis-specific factor(s) to result in biofilm enhancement.

PMID- 16109964
TI  - Using multilocus sequence data to define the pneumococcus.
AB  - We investigated the genetic relationships between serotypeable pneumococci and
      nonserotypeable presumptive pneumococci using multilocus sequence typing (MLST)
      and partial sequencing of the pneumolysin gene (ply). Among 121 nonserotypeable
      presumptive pneumococci from Finland, we identified isolates of three classes:
      those with sequence types (STs) identical to those of serotypeable pneumococci,
      suggesting authentic pneumococci in which capsular expression had been
      downregulated or lost; isolates that clustered among serotypeable pneumococci on
      a tree based on the concatenated sequences of the MLST loci but which had STs
      that differed from those of serotypeable pneumococci in the MLST database; and a
      more diverse collection of isolates that did not cluster with serotypeable
      pneumococci. The latter isolates typically had sequences at all seven MLST loci
      that were 5 to 10% divergent from those of authentic pneumococci and also had
      distinct and divergent ply alleles. These isolates are proposed to be distinct
      from pneumococci but cannot be resolved from them by optochin susceptibility,
      bile solubility, or the presence of the ply gene. Complete resolution of
      pneumococci from the related but distinct population is problematic, as
      recombination between them was evident, and a few isolates of each population
      possessed alleles at one or occasionally more MLST loci from the other
      population. However, a tree based on the concatenated sequences of the MLST loci
      in most cases unambiguously distinguished whether a nonserotypeable isolate was
      or was not a pneumococcus, and the sequence of the ply gene fragment was found to
      be useful to resolve difficult cases.

PMID- 16109966
TI  - Implications of physiological studies based on genomic sequences: Streptococcus
      pneumoniae TIGR4 synthesizes a functional LytC lysozyme.
AB  - The Streptococcus pneumoniae LytC lysozyme is responsible for autolysis at 30
      degrees C (a temperature close to that of the upper respiratory tract), promotes
      DNA release in competent cultures, and participates in nasopharyngeal
      colonization. We show that the virulent pneumococcal TIGR4 strain encodes an
      active LytC enzyme, in contrast with genome-based predictions.

PMID- 16109965
TI  - Xanthomonas campestris pv. campestris possesses a single gluconeogenic pathway
      that is required for virulence.
AB  - Disruption of ppsA, a key gene in gluconeogenesis, of Xanthomonas campestris pv.
      campestris resulted in the failure of the pathogen to grow in medium with
      pyruvate or C4-dicarboxylates as the sole carbon source and a significant
      reduction in virulence, indicating that X. campestris pv. campestris possesses
      only the malic enzyme-PpsA route in gluconeogenesis, which is required for
      virulence.

PMID- 16109967
TI  - OpsX from Haemophilus influenzae represents a novel type of heptosyltransferase I
      in lipopolysaccharide biosynthesis.
AB  - The inner core region of the lipopolysaccharide (LPS) of Haemophilus influenzae
      is characterized by the presence of a phosphorylated 3-deoxy-alpha-D-manno
      octulosonic acid (Kdo). In this study, we show that the heptosyltransferase I
      adding the first L-glycero-D-manno-heptose residue to this acceptor is encoded by
      the gene opsX, which differs in substrate specificity from the other
      heptosyltransferase I, known as WaaC.

PMID- 16109968
TI  - Acquisition of insertion sequences and the GBSi1 intron by Streptococcus
      agalactiae isolates correlates with the evolution of the species.
AB  - The prevalence of insertion sequences IS1548, IS861, IS1381, and ISSa4 and of the
      group II intron GBSi1 within Streptococcus agalactiae human isolates strongly
      correlates with the genetic lineages obtained by multilocus sequence typing. Our
      results yielded an evolutionary scheme for the acquisition of these genetic
      elements linked to the ecosystems from which the isolates were obtained.

PMID- 16109969
TI  - Genome-wide HP1 binding in Drosophila: developmental plasticity and genomic
      targeting signals.
AB  - Heterochromatin protein 1 (HP1) is a major component of heterochromatin. It was
      reported to bind to a large number of genes and to many, but not all,
      transposable elements (TEs). The genomic signals responsible for targeting of HP1
      have remained elusive. Here, we use whole-genome and computational approaches to
      identify genomic features that are predictive of HP1 binding in Drosophila
      melanogaster. We show that genes in repeat-dense regions are more likely to be
      bound by HP1, particularly in pericentric chromosomal regions. We also
      demonstrate that TEs are only bound by HP1 if they are flanked by other repeats,
      suggesting a cooperative mechanism of binding. Genome-wide DamID mapping of HP1
      in larvae and adult flies reveals that repeat-flanked genes typically bind HP1
      throughout development, whereas repeat-free genes display developmentally dynamic
      HP1 association. Furthermore, computational analysis shows that HP1
      preferentially binds to transcribed regions of long genes. Finally, we detect low
      but significant amounts of HP1 along the entire X chromosome in male, but not
      female, flies, suggesting a link between HP1 and the dosage compensation complex.
      These results provide insights into the mechanisms of HP1 targeting in the
      natural genomic context.

PMID- 16109970
TI  - A network of transcriptionally coordinated functional modules in Saccharomyces
      cerevisiae.
AB  - Recent computational and experimental work suggests that functional modules
      underlie much of cellular physiology and are a useful unit of cellular
      organization from the perspective of systems biology. Because interactions among
      modules can give rise to higher-level properties that are essential to cellular
      function, a complete knowledge of these interactions is necessary for future work
      in systems biology, including in silico modeling and metabolic engineering. Here
      we present a computational method for the systematic identification and analysis
      of functional modules whose activity is coordinated at the level of
      transcription. We applied this method, Search for Pairwise Interactions (SPIN),
      to obtain a global view of functional module connectivity in Saccharomyces
      cerevisiae and to provide insight into the biological mechanisms underlying this
      coordination. We also examined this global network at higher resolution to obtain
      detailed information about the interactions of particular module pairs. For
      instance, our results reveal possible transcriptional coordination of glycolysis
      and lipid metabolism by the transcription factor Gcr1p, and further suggest that
      glycolysis and phosphoinositide signaling may regulate each other reciprocally.

PMID- 16109971
TI  - Sequence, annotation, and analysis of synteny between rice chromosome 3 and
      diverged grass species.
AB  - Rice (Oryza sativa L.) chromosome 3 is evolutionarily conserved across the
      cultivated cereals and shares large blocks of synteny with maize and sorghum,
      which diverged from rice more than 50 million years ago. To begin to completely
      understand this chromosome, we sequenced, finished, and annotated 36.1 Mb (
      approximately 97%) from O. sativa subsp. japonica cv Nipponbare. Annotation
      features of the chromosome include 5915 genes, of which 913 are related to
      transposable elements. A putative function could be assigned to 3064 genes, with
      another 757 genes annotated as expressed, leaving 2094 that encode hypothetical
      proteins. Similarity searches against the proteome of Arabidopsis thaliana
      revealed putative homologs for 67% of the chromosome 3 proteins. Further searches
      of a nonredundant amino acid database, the Pfam domain database, plant Expressed
      Sequence Tags, and genomic assemblies from sorghum and maize revealed only 853
      nontransposable element related proteins from chromosome 3 that lacked similarity
      to other known sequences. Interestingly, 426 of these have a paralog within the
      rice genome. A comparative physical map of the wild progenitor species, Oryza
      nivara, with japonica chromosome 3 revealed a high degree of sequence identity
      and synteny between these two species, which diverged approximately 10,000 years
      ago. Although no major rearrangements were detected, the deduced size of the O.
      nivara chromosome 3 was 21% smaller than that of japonica. Synteny between rice
      and other cereals using an integrated maize physical map and wheat genetic map
      was strikingly high, further supporting the use of rice and, in particular,
      chromosome 3, as a model for comparative studies among the cereals.

PMID- 16109972
TI  - ATG deserts define a novel core promoter subclass.
AB  - The MHC class I gene, PD1, has neither functional TATAA nor Initiator (Inr)
      elements in its core promoter and initiates transcription at multiple, dispersed
      sites over an extended region in vitro. Here, we define a novel core promoter
      feature that supports regulated transcription through selective transcription
      start site (TSS) usage. We demonstrate that TSS selection is actively regulated
      and context dependent. Basal and activated transcriptions initiate from largely
      nonoverlapping TSS regions. Transcripts derived from multiple TSS encode a single
      protein, due to the absence of any ATG triplets within approximately 430 bp
      upstream of the major transcription start site. Thus, the PD1 core promoter is
      embedded within an "ATG desert". Remarkably, extending this analysis genome-wide,
      we find that ATG deserts define a novel promoter subclass. They occur
      nonrandomly, are significantly associated with non-TATAA promoters that use
      multiple TSS, independent of the presence of CpG islands (CGI). We speculate that
      ATG deserts may provide a core promoter platform upon which complex upstream
      regulatory signals can be integrated, targeting multiple TSS whose products
      encode a single protein.

PMID- 16109973
TI  - Comparative genomics of Gossypium and Arabidopsis: unraveling the consequences of
      both ancient and recent polyploidy.
AB  - Both ancient and recent polyploidy, together with post-polyploidization loss of
      many duplicated gene copies, complicates angiosperm comparative genomics. To
      explore an approach by which these challenges might be mitigated, genetic maps of
      extant diploid and tetraploid cottons (Gossypium spp.) were used to infer the
      approximate order of 3016 loci along the chromosomes of their hypothetical common
      ancestor. The inferred Gossypium gene order corresponded more closely than the
      original maps did to a similarly inferred ancestral gene order predating an
      independent paleopolyploidization (alpha) in Arabidopsis. At least 59% of the
      cotton map and 53% of the Arabidopsis transcriptome showed correspondence in
      multilocus gene arrangements based on one or both of two software packages
      (CrimeStatII, FISH). Genomic regions in which chromosome structural rearrangement
      has been rapid (obscuring gene order correspondence) have also been subject to
      greater divergence of individual gene sequences. About 26%-44% of corresponding
      regions involved multiple Arabidopsis or cotton chromosomes, in some cases
      consistent with known, more ancient, duplications. The genomic distributions of
      multiple-locus probes provided early insight into the consequences for chromosome
      structure of an ancient large-scale duplication in cotton. Inferences that
      mitigate the consequences of ancient duplications improve leveraging of genomic
      information for model organisms in the study of more complex genomes.

PMID- 16109974
TI  - Origin and evolution of new exons in rodents.
AB  - Gene number difference among organisms demonstrates that new gene origination is
      a fundamental biological process in evolution. Exon shuffling has been
      universally observed in the formation of new genes. Yet to be learned are the
      ways new exons originate and evolve, and how often new exons appear. To address
      these questions, we identified 2695 newly evolved exons in the mouse and rat by
      comparing the expressed sequences of 12,419 orthologous genes between human and
      mouse, using 743,856 pig ESTs as the outgroup. The new exon origination rate is
      about 2.71 x 10(-3) per gene per million years. These new exons have markedly
      accelerated rates both of nonsynonymous substitutions and of insertions/deletions
      (indels). A much higher proportion of new exons have K(a)/K(s) ratios >1 (where
      K(a) is the nonsynonymous substitution rate and K(s) is the synonymous
      substitution rate) than do the old exons shared by human and mouse, implying a
      role of positive selection in the rapid evolution. The majority of these new
      exons have sequences unique in the genome, suggesting that most new exons might
      originate through "exonization" of intronic sequences. Most of the new exons
      appear to be alternative exons that are expressed at low levels.

PMID- 16109975
TI  - The zebrafish gene map defines ancestral vertebrate chromosomes.
AB  - Genetic screens in zebrafish (Danio rerio) have identified mutations that define
      the roles of hundreds of essential vertebrate genes. Genetic maps can link mutant
      phenotype with gene sequence by providing candidate genes for mutations and
      polymorphic genetic markers useful in positional cloning projects. Here we report
      a zebrafish genetic map comprising 4073 polymorphic markers, with more than twice
      the number of coding sequences localized in previously reported zebrafish genetic
      maps. We use this map in comparative studies to identify numerous regions of
      synteny conserved among the genomes of zebrafish, Tetraodon, and human. In
      addition, we use our map to analyze gene duplication in the zebrafish and
      Tetraodon genomes. Current evidence suggests that a whole-genome duplication
      occurred in the teleost lineage after it split from the tetrapod lineage, and
      that only a subset of the duplicates have been retained in modern teleost
      genomes. It has been proposed that differential retention of duplicate genes may
      have facilitated the isolation of nascent species formed during the vast
      radiation of teleosts. We find that different duplicated genes have been retained
      in zebrafish and Tetraodon, although similar numbers of duplicates remain in both
      genomes. Finally, we use comparative mapping data to address the proposal that
      the common ancestor of vertebrates had a genome consisting of 12 chromosomes. In
      a three-way comparison between the genomes of zebrafish, Tetraodon, and human,
      our analysis delineates the gene content for 11 of these 12 proposed ancestral
      chromosomes.

PMID- 16109976
TI  - Recruited inflammatory cells mediate endotoxin-induced lung maturation in preterm
      fetal lambs.
AB  - RATIONALE: Chorioamnionitis is paradoxically associated with a decreased
      incidence of respiratory distress syndrome in preterm infants. In preterm lambs,
      intraamniotic endotoxin and interleukin 1 (IL-1) induce lung inflammation
      followed by lung maturation. OBJECTIVE: To test if inflammatory cells are
      required to mediate induced lung maturation. METHODS: Lung inflammation was
      induced by intraamniotic injection of endotoxin or IL-1. Inflammatory cell
      recruitment to the lung was inhibited by an anti-CD18 blocking antibody given
      intramuscularly to the fetus. Preterm lambs were delivered at 124-d gestation
      (term = 150 d) 2 or 7 d after exposure to endotoxin/IL-1 or endotoxin/IL-1 + anti
      CD18 antibody. MEASUREMENTS: Lung inflammation was measured by bronchoalveolar
      lavage fluid cell count, inflammatory scoring of lung parenchyma, and expression
      of proinflammatory cytokines and inducible nitric oxide synthase. Lung maturation
      was quantitated by surfactant protein mRNA expression, saturated
      phosphatidylcholine pool size, and pressure-volume curves. MAIN RESULTS:
      Inhibition of CD18 significantly reduced endotoxin-induced but not IL-1-induced
      fetal lung inflammatory cell recruitment and activation as well as expression of
      proinflammatory cytokines. Compared with control lungs, both endotoxin and IL-1
      induced lung maturation. Anti-CD18 antibody administration inhibited only
      endotoxin-induced but not IL-1-induced increases in surfactant protein mRNA and
      surfactant saturated phosphatidylcholine. Exposure to anti-CD18 antibody
      moderated endotoxin-induced increases in lung volumes but had no effect on IL-1
      induced increases in lung volumes. CONCLUSIONS: (1) Endotoxin- but not IL-1
      induced inflammatory cell recruitment in the preterm fetal lamb lung is CD18
      dependent; (2) recruited inflammatory cells mediate some aspects of fetal lung
      maturation.

PMID- 16109977
TI  - Diaphragm length and neural drive after lung volume reduction surgery.
AB  - RATIONALE: Patients with chronic obstructive pulmonary disease have shorter
      inspiratory muscles and higher motor unit firing rates during quiet breathing
      than do age-matched healthy subjects. Lung volume reduction surgery (LVRS) in
      patients with chronic obstructive pulmonary disease improves lung function,
      exercise capacity, and quality of life. OBJECTIVES: We studied the effect of LVRS
      on length and motor unit firing rates of diaphragm and scalene muscles. METHODS:
      Diaphragm length was estimated by ultrasound and magnetometers, and firing rates
      were recorded with needle electrodes in patients (five females and seven males)
      with severe chronic obstructive pulmonary disease, before and after surgery.
      MEASUREMENTS AND MAIN RESULTS: Pre-LVRS total lung capacity was 135 +/- 10%
      predicted (mean +/- SD), and FEV1 was 30 +/- 12% predicted. After surgery, median
      firing frequency of diaphragmatic motor units fell from 17.3 +/- 4.2 to 14.5 +/-
      3.4 Hz (p < 0.001), and scalene motor unit firing rates were reduced from 15.3 +/
      6.9 to 13.4 +/- 3.8 Hz (p < 0.001). Tidal volume and diaphragm length change
      during quiet breathing did not change, but at end expiration, the zone of
      apposition length of diaphragm against the rib cage (L(Zapp)) increased (30 +/-
      28%, p = 0.004). Improvements in quality-of-life measures and exercise
      performance after surgery were related to increased forced vital capacity and
      L(Zapp). CONCLUSIONS: Increased diaphragm length resulted in lower motor unit
      firing rates and reduced breathing effort, and this is likely to contribute to
      improved quality of life and exercise performance after LVRS.

PMID- 16109978
TI  - Clinical and pathologic features of familial interstitial pneumonia.
AB  - RATIONALE: Several lines of evidence suggest that genetic factors and
      environmental exposures play a role in the development of pulmonary fibrosis.
      OBJECTIVES: We evaluated families with 2 or more cases of idiopathic interstitial
      pneumonia among first-degree family members (familial interstitial pneumonia, or
      FIP), and identified 111 families with FIP having 309 affected and 360 unaffected
      individuals. METHODS: The presence of probable or definite FIP was based on
      medical record review in 28 cases (9.1%); clinical history, diffusing capacity of
      carbon monoxide (DL(CO)), and chest X-ray in 16 cases (5.2%); clinical history,
      DL(CO), and high-resolution computed tomography chest scan in 191 cases (61.8%);
      clinical history and surgical lung biopsy in 56 cases (18.1%); and clinical
      history and autopsy in 18 cases (5.8%). RESULTS: Older age (68.3 vs. 53.1; p <
      0.0001), male sex (55.7 vs. 37.2%; p < 0.0001), and having ever smoked cigarettes
      (67.3 vs. 34.1%; p < 0.0001) were associated with the development of FIP. After
      controlling for age and sex, having ever smoked cigarettes remained strongly
      associated with the development of FIP (odds ratio(adj), 3.6; 95% confidence
      interval, 1.3-9.8). Evidence of aggregation of disease was highly significant (p
      < 0.001) among sibling pairs, and 20 pedigrees demonstrated vertical
      transmission, consistent with autosomal dominant inheritance. Forty-five percent
      of pedigrees demonstrated phenotypic heterogeneity, with some pedigrees
      demonstrating several subtypes of idiopathic interstitial pneumonia occurring
      within the same families. CONCLUSIONS: These findings suggest that FIP may be
      caused by an interaction between a specific environmental exposure and a gene (or
      genes) that predisposes to the development of several subtypes of idiopathic
      interstitial pneumonia.

PMID- 16109979
TI  - Using protein microarray as a diagnostic assay for non-small cell lung cancer.
AB  - RATIONALE: Phenotypic and genotypic heterogeneity of lung cancer likely precludes
      the identification of a single predictive marker and suggests the importance of
      identifying and measuring multiple markers. OBJECTIVES: We describe the use of a
      fluorescent protein microarray to identify and measure multiple non-small cell
      lung cancer-associated antibodies and show how simultaneous measurements can be
      combined into a single diagnostic assay. METHODS: T7 phage cDNA libraries of non
      small cell lung cancer were first biopanned with plasma samples from normal
      subjects and patients with non-small cell lung cancer to enrich the component of
      tumor-associated proteins, and then applied to microarray slides. Two hundred
      twelve immunogenic phage-expressed proteins were identified from roughly 4,000
      clones, using high-throughput screening with patient plasmas and assayed with 40
      cancer and 41 normal plasma samples. Twenty patient and 21 normal plasma samples
      were randomly chosen and used for statistical determination of the predictive
      value of each putative marker. Statistical analysis identified antibody
      reactivity to seven unique phage-expressed proteins that were significantly
      different (p < 0.01) between patient and normal groups. The remaining 20 patient
      and 20 normal plasma samples were used as an independent test of the predictive
      ability of the selected markers. MAIN RESULTS: Measurements of the 5 most
      predictive phage proteins were combined in a logistic regression model that
      achieved 90% sensitivity and 95% specificity in prediction of patient samples,
      whereas leave-one-out statistical analysis achieved 88.9% diagnostic accuracy
      among all 81 samples. CONCLUSION: Our data indicate that antibody profiling is a
      promising approach that could achieve high diagnostic accuracy for non-small cell
      lung cancer.

PMID- 16109980
TI  - Outcome of asthma and wheezing in the first 6 years of life: follow-up through
      adolescence.
AB  - RATIONALE: The effect of early life wheezing on respiratory function and
      continued symptoms through adolescence has not been fully described. Using data
      from a population-based birth cohort in Tucson, Arizona, we previously described
      four phenotypes based on the occurrence of wheezing lower respiratory illnesses
      before age 3 yr and active wheeze at age 6 yr: never wheezers (n = 425),
      transient early wheezers (n = 164), persistent wheezers (n = 113), and late-onset
      wheezers (n = 124). OBJECTIVE: We sought to determine the prognosis for these
      phenotypes, with reference to lung function and symptoms, through adolescence.
      METHODS: Current wheeze was assessed by questionnaire, lung function was measured
      by conventional spirometry, and atopy was determined by skin prick tests.
      RESULTS: The prevalence of atopy and wheeze by age 16 yr was similar for never
      and transient wheezers and for persistent and late-onset wheezers. Both transient
      early, and persistent wheezers had significantly lower FEF(25-75) (-259 ml/s, p <
      0.001, and -260 ml/s, p = 0.001, respectively), FEV1 (-75 ml, p = 0.02, and -87
      ml, p = 0.03, respectively), and FEV1:FVC ratio (-1.9%, p = 0.002, and -2.5%, p =
      0.001, respectively) through age 16 yr compared with never wheezers. Late-onset
      wheezers had levels of lung function similar to those of never wheezers through
      age 16 yr. There was no significant change in lung function among subjects with
      any of the four phenotypes, relative to their peers, from age 6 to 16 yr.
      CONCLUSION: Patterns of wheezing prevalence and levels of lung function are
      established by age 6 yr and do not appear to change significantly by age 16 yr in
      children who start having asthma-like symptoms during the preschool years.

PMID- 16109981
TI  - Acquired rifamycin resistance with twice-weekly treatment of HIV-related
      tuberculosis.
AB  - RATIONALE: Rifabutin was recommended in place of rifampin during treatment of HIV
      related tuberculosis (TB) to facilitate concomitant potent antiretroviral
      therapy, but this approach has not been evaluated in a prospective study.
      OBJECTIVE: To evaluate the activity of intermittent rifabutin-based therapy.
      METHODS: Patients with culture-confirmed TB were treated under direct supervision
      with 2 mo of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily,
      thrice-weekly, or twice-weekly per the local tuberculosis control program),
      followed by 4 mo of twice-weekly rifabutin plus isoniazid. MEASUREMENTS: Culture
      positive treatment failure or relapse. MAIN RESULTS: A total of 169 eligible
      patients were enrolled. Most had advanced HIV disease; the median CD4 cell count
      and HIV-RNA level were 90 cells/mm3 (interquartile range, 35-175) and 5.3 log10
      copies/ml (interquartile range, 4.8-5.7), respectively. Nine (5.3%) patients had
      culture-positive treatment failure (n = 3) or relapse (n = 6). Eight of these
      nine (89%) cases had isolates with acquired rifamycin resistance. Treatment
      failure or relapse was associated with baseline CD4 lymphocyte count, being 12.3%
      (9/73; 95% confidence interval, 6.5-22.0%) among patients with CD4 < 100
      cells/mm3 versus 0% (0/65; 95% confidence interval, 0.0-4.5%) among those with
      higher CD4 lymphocyte counts (p < 0.01). One hundred thirty-seven (81%) patients
      received antiretroviral therapy during TB treatment. Adverse events were common,
      but only two patients (1%) permanently discontinued study drugs. CONCLUSIONS:
      Intermittent rifabutin-based therapy for HIV-related TB was well tolerated, but
      there was a high risk of treatment failure or relapse with acquired rifamycin
      resistance among patients with low CD4 lymphocyte counts.

PMID- 16109983
TI  - Impact of expiratory trigger setting on delayed cycling and inspiratory muscle
      workload.
AB  - RATIONALE: During pressure-support ventilation, the ventilator cycles into
      expiration when inspiratory flow decreases to a given percentage of peak
      inspiratory flow ("expiratory trigger"). In obstructive disease, the slower rise
      and decrease of inspiratory flow entails delayed cycling, an increase in
      intrinsic positive end-expiratory pressure, and nontriggering breaths.
      OBJECTIVES: We hypothesized that setting expiratory trigger at a higher than
      usual percentage of peak inspiratory flow would attenuate the adverse effects of
      delayed cycling. METHODS: Ten intubated patients with obstructive disease
      undergoing pressure support were studied at expiratory trigger settings of 10,
      25, 50, and 70% of peak inspiratory flow. MEASUREMENTS: Continuous recording of
      diaphragmatic EMG activity with surface electrodes, and esophageal and gastric
      pressures with a dual-balloon nasogastric tube. MAIN RESULTS: Compared with
      expiratory trigger 10, expiratory trigger 70 reduced the magnitude of delayed
      cycling (0.25 +/- 0.18 vs. 1.26 +/- 0.72 s, p < 0.05), intrinsic positive end
      expiratory pressure (4.8 +/- 1.9 vs. 6.5 +/- 2.2 cm H(2)O, p < 0.05),
      nontriggering breaths (2 +/- 3 vs. 9 +/- 5 breaths/min, p < 0.05), and triggering
      pressure-time product (0.9 +/- 0.8 vs. 2.1 +/- 0.7 cm H2O . s, p < 0.05).
      CONCLUSIONS: Setting expiratory trigger at a higher percentage of peak
      inspiratory flow in patients with obstructive disease during pressure support
      improves patient-ventilator synchrony and reduces inspiratory muscle effort.
      Further studies should explore whether these effects can influence patient
      outcome.

PMID- 16109982
TI  - Inhibition of acid-induced lung injury by hyperosmolar sucrose in rats.
AB  - RATIONALE: Acid aspiration causes acute lung injury (ALI). Recently, we showed
      that a brief intravascular infusion of hyperosmolar sucrose, given concurrently
      with airway acid instillation, effectively blocks the ensuing ALI. OBJECTIVES:
      The objective of the present study was to determine the extent to which
      intravascular infusion of hyperosmolar sucrose might protect against acid-induced
      ALI when given either before or after acid instillation. METHODS: Our studies
      were conducted in anesthetized rats and in isolated, blood-perfused rat lungs. We
      instilled HCl through the airway, and we quantified lung injury in terms of the
      extravascular lung water (EVLW) content, filtration coefficient (Kfc), and cell
      counts and protein concentration in the bronchoalveolar lavage. We infused
      hyperosmolar sucrose via the femoral vein. RESULTS: In anesthetized rats, airway
      HCl instillation induced ALI as indicated by a 52% increase of EVLW and a
      threefold increase in Kfc. However, a 15-min intravenous infusion of hyperosmolar
      sucrose given up to 1 h before or 30 min after acid instillation markedly blunted
      the increases in EVLW, as well as the increases in cell count, and in protein
      concentration in the bronchoalveolar lavage. Hyperosmolar pretreatment also
      blocked the acid-induced increase of Kfc. Studies in isolated perfused lungs
      indicated that the protective effect of hyperosmolar sucrose was leukocyte
      independent. CONCLUSIONS: We conclude that a brief period of vascular
      hyperosmolarity protects against acid-induced ALI when the infusion is
      administered shortly before, or shortly after, acid instillation in the airway.
      The potential applicability of hyperosmolar sucrose in therapy for ALI requires
      consideration.

PMID- 16109984
TI  - Fiber-type composition of the human jaw muscles--(part 1) origin and functional
      significance of fiber-type diversity.
AB  - This is the first of two articles on the fiber-type composition of the human jaw
      muscles. The present article discusses the origin of fiber-type composition and
      its consequences. This discussion is presented in the context of the requirements
      for functional performance and adaptation that are imposed upon the jaw muscles.
      The human masticatory system must perform a much larger variety of motor tasks
      than the average limb or trunk motor system. An important advantage of fiber-type
      diversity, as observed in the jaw muscles, is that it optimizes the required
      function while minimizing energy use. The capacity for adaptation is reflected by
      the large variability in fiber-type composition among muscle groups, individual
      muscles, and muscle regions. Adaptive changes are related, for example, to the
      amount of daily activation and/or stretch of fibers. Generally, the number of
      slow, fatigue-resistant fibers is relatively large in muscles and muscle regions
      that are subjected to considerable activity and/or stretch.

PMID- 16109985
TI  - Fiber-type composition of the human jaw muscles--(part 2) role of hybrid fibers
      and factors responsible for inter-individual variation.
AB  - This is the second of two articles about fiber-type composition of the human jaw
      muscles. It reviews the functional relationship of hybrid fibers and the adaptive
      properties of jaw-muscle fibers. In addition, to explain inter-individual
      variation in fiber-type composition, we discuss these adaptive properties in
      relation to environmental stimuli or perturbations. The fiber-type composition of
      the human jaw muscles is very different from that of limb and trunk muscles.
      Apart from the presence of the usual type I, IIA, and IIX myosin heavy-chains
      (MyHC), human jaw-muscle fibers contain MyHCs that are typical for developing or
      cardiac muscle. In addition, much more frequently than in limb and trunk muscles,
      jaw-muscle fibers are hybrid, i.e., they contain more than one type of MyHC
      isoform. Since these fibers have contractile properties that differ from those of
      pure fibers, this relatively large quantity of hybrid fibers provides a mechanism
      that produces a very fine gradation of force and movement. The presence of hybrid
      fibers might also reflect the adaptive capacity of jaw-muscle fibers. The
      capacity for adaptation also explains the observed large inter-individual
      variability in fiber-type composition. Besides local influences, like the amount
      of muscle activation and/or stretch, more general influences, like aging and
      gender, also play a role in the composition of fiber types.

PMID- 16109986
TI  - Cost-effectiveness of mandibular two-implant overdentures and conventional
      dentures in the edentulous elderly.
AB  - Implementation of new therapies is usually governed by financial considerations,
      so efficacy studies should also include cost comparisons. The cost and
      effectiveness of mandibular conventional dentures (CD, n = 30) and two-implant
      overdentures (IOD, n = 30) were compared in elderly subjects. Effectiveness (Oral
      Health Impact Profile, OHIP-20) and cost were measured up to one year post
      treatment. Data for subsequent years were estimated by the Delphi method. Using
      an average life expectancy of 17.9 years, the equalized annual costs (in Canadian
      dollars) were dollar 399 for CD and dollar 625 for IOD (p < 0.001), and the
      equalized annual values for the outcome (OHIP-20) were 47.0 for CD and 31.3 for
      IOD treatment (p < 0.05). These values translate into a yearly additional cost
      for IOD treatment of dollar 14.41 per OHIP-20 point. These results are key to the
      implementation of programs to provide this form of therapy for edentulous adults.

PMID- 16109987
TI  - Environmental and heritable factors in the etiology of oral diseases--a
      population-based study of Swedish twins.
AB  - A population-based twin study is a useful design for quantification of the
      effects of genes and environmental factors in disease etiology. We used data from
      10,000 Swedish twin pairs to quantify genetic and environmental contributions to
      tooth loss and periodontal health. Oral health information was obtained from
      telephone interviews. Structural equation models measured the relative importance
      of genetic and environmental factors. Genetic factors contributed to 14% of
      variation in tooth loss among women, and 39% among men. Non-shared environmental
      factors accounted for one-quarter of risk; environmental factors shared by twins
      comprised the remainder. Heritability estimates of periodontal disease were 39%
      and 33% for women and men, respectively, while non-shared environmental factors
      accounted for the remaining variation. Heritability for both conditions varied as
      a function of age and smoking status. Analysis of data from this large,
      population-based study demonstrates a moderate role of genetic factors in oral
      diseases, and suggests potential gene-environment interactions.

PMID- 16109988
TI  - Mode of delivery and other maternal factors influence the acquisition of
      Streptococcus mutans in infants.
AB  - S. mutans plays a key role in dental caries. The extent to which perinatal events
      influence the acquisition of S. mutans is unclear. We hypothesized that several
      maternal factors, including the mode of delivery, influence the initial
      acquisition of S. mutans in infants. A prospective cohort study was conducted in
      156 mother-infant pairs. The study found that maternal gestational age (p =
      0.04), S. mutans level (p = 0.02), caries score (p = 0.02), sexually transmitted
      disease (STD) infection experience (p = 0.01), and family income (p = 0.03) had
      significant effects on the acquisition of S. mutans. Among infants who became
      infected, those delivered by Caesarean section acquired S. mutans 11.7 mos
      earlier than did vaginally delivered infants (p = 0.038). C-section infants
      harbored a single genotype of S. mutans that was identical to that of their
      mothers (100% fidelity). Analysis of the data demonstrated the possible perinatal
      influences on infants' acquisition of a member of the cariogenic microbiota, and
      its potential effect on caries outcome.

PMID- 16109989
TI  - Polymorphisms in PTCH1 affect the risk of ameloblastoma.
AB  - Ameloblastoma is the most common odontogenic tumor, but the genetic nature of the
      changes in the tumor cells has been unclear. Mutations of CTNNB1 or PTCH1 are
      observed in many human tumors. Both CTNNB1 and PTCH1 are important in tooth
      development and are expressed in ameloblastoma. The aim of this study was to
      investigate whether genetic alterations of CTNNB1 and PTCH1 are present in
      ameloblastoma. We investigated 14 cases of ameloblastoma. The polymorphisms found
      in the ameloblastoma patients were further examined in a subsequent case-control
      study. We found a CTNNB1 mutation in one case of plexiform-type ameloblastoma.
      CGG triplet repeat-number polymorphism (CGG7/CGG8) in the 5'-untranslated region
      of PTCH1 was observed. The proportion of CGG8 alleles was significantly higher in
      the ameloblastoma group. The results of this study indicate a possible
      relationship between the CGG8 allele in PTCH1 and the risk for ameloblastoma.

PMID- 16109990
TI  - Bayesian analysis of clustered interval-censored data.
AB  - The recording of multiple interval-censored failure times is common in dental
      research. Modeling multilevel data has been a difficult task. This paper aims to
      use the Bayesian approach to analyze a set of multilevel clustered interval
      censored data from a clinical study to investigate the effectiveness of silver
      diamine fluoride and sodium fluoride varnish in arresting active dentin caries in
      Chinese pre-school children. The time to arrest dentin caries on a surface was
      measured. A three-level random-effects Weibull regression model was used.
      Analysis was performed with WinBUGS. Results revealed a strong positive
      correlation (0.596) among the caries lesions' arrest times on different surfaces
      from the same child. The software WinBUGS made the above complicated estimation
      simple. In conclusion, the annual application of silver diamine fluoride on
      caries lesions, and caries removal before the application, were found to shorten
      the arrest time.

PMID- 16109991
TI  - Impact of curing protocol on conversion and shrinkage stress.
AB  - Since considerable shrinkage stress develops during the curing of dental
      composites, various soft-start photocuring protocols, aiming to lower stress but
      not compromise conversion, have been proposed. We hypothesized that utilizing
      soft-start photocuring will result in not only reduced stress, but also decreased
      conversion. We evaluated the impact of 3 protocols (soft-start, pulse, and
      standard) on the stress development and polymerization extent of an experimental
      composite. A novel set-up capable of simultaneous shrinkage stress, conversion,
      and temperature measurements on the same specimen was utilized. Analysis of the
      data shows that stress rises dramatically as a function of conversion in the
      vitrified state, and the utilization of soft-start or pulse curing results in
      specimens with reduced final conversion and shrinkage stress, compared with
      specimens cured according to the standard full-intensity protocol. Finally, this
      study demonstrates that the predominant reason for the reduced shrinkage stress
      attained with soft-start or pulse curing is a modest decrease in final
      conversion.

PMID- 16109992
TI  - Colloidal beta-tricalcium phosphate prepared by discharge in a modified body
      fluid facilitates synthesis of collagen composites.
AB  - The development of hydroxyapatite/collagen composites that are naturally
      synthesized and need no additional treatment is required for use in bone repair.
      Since reducing the diameter can increase the specific surface area of calcium
      phosphate particles that can conjugate collagen molecules, we expected colloidal
      calcium phosphates of submicron diameter obtained by discharge to be effective in
      formulating these composites. Additionally, since biodegradable beta-tricalcium
      phosphate has better osteoconductivity than hydroxyapatite, this study aimed to
      investigate the synthesis of colloidal hydroxyapatite and beta-tricalcium
      phosphate/collagen composites. Collagen molecules were tightly polymerized in the
      beta-tricalcium phosphate/collagen composite by catalysis of the generated -P-O-P
      polyphosphate chain. Bonding strength between collagen NH+ amino groups and -P-O
      P-, and cross-linking of the Ca++-RCOO- in the collagen were increased compared
      with those in the hydroxyapatite/collagen composite. These chemical reactions due
      to colloidal beta-tricalcium phosphate might play a key role in the synthesis of
      collagen composites.

PMID- 16109993
TI  - Fluorosis: a new model and new insights.
AB  - Fluoride is an effective agent for the prevention of dental caries. However, the
      mechanism of how excessive fluoride exposure causes fluorosis remains uncertain.
      Zebrafish (Danio rerio) exhibit periodic tooth replacement throughout their
      lives, thereby providing continuous access to teeth at developmental stages
      susceptible to fluoride exposure. Zebrafish teeth do not contain true enamel, but
      consist of a hard enameloid surface. Therefore, we asked whether zebrafish could
      be used as a model organism for the study of dental fluorosis. Scanning electron
      microscopy of fluoride-treated teeth demonstrated that the enameloid was pitted
      and rough, and FTIR analysis demonstrated that the teeth also contained a
      significantly higher organic content when compared with untreated controls.
      Furthermore, we demonstrate for the first time that decreased expression of an
      important signaling molecule (Alk8) in tooth development may contribute to the
      observed fluorotic phenotype, and that increased cell apoptosis may also play a
      role in the mechanism of fluorosis.

PMID- 16109995
TI  - Isolation and expression of FIP-2 in wounded pulp of the rat.
AB  - Pulpal wound healing followed by cavity preparation may involve reactionary or
      reparative dentinogenesis in relation to the cavity position; however, little is
      known about the molecular responses. We aimed to isolate and analyze genes
      induced or suppressed in the wounded pulp to identify molecular processes
      involved in the pulp responses to injury. Twenty-three cDNAs were isolated by
      cDNA subtraction between healthy and wounded pulp of rats. By library screening,
      we identified rat 14.7K-interacting protein (rFIP)-2A and B genes homologous to
      human FIP-2, being involved in regulating membrane trafficking and cellular
      morphogenesis. RT-PCR analysis showed induction for only rFIP-2B in the wounded
      pulp. In situ hybridization analysis revealed that both rFIP-2s were expressed
      strongly in condensing mesenchymal cells of the palatal process and surrounding
      Meckel's cartilage, but not in intramembranous chondrogenic cells. Thus, up
      regulated rFIP-2B expression may play a role in regulating membrane trafficking
      or cellular morphogenesis of these embryonic and wounded pulpal cells.

PMID- 16109994
TI  - CSF-1 regulation of osteoclastogenesis for tooth eruption.
AB  - The dental follicle regulates the alveolar bone resorption needed for tooth
      eruption. In the rat first mandibular molar, a decrease in the expression of
      osteoprotegerin (OPG) in the dental follicle at day 3 enables the
      osteoclastogenesis needed for eruption to occur. Because colony-stimulating
      factor-1 (CSF-1) is maximally expressed in the dental follicle at day 3, it was
      hypothesized that CSF-1 down-regulates OPG gene expression in the dental follicle
      in vivo. To test this, we compared the expression of OPG in osteopetrotic
      toothless (tl/tl) rats deficient in CSF-1 with expression in their normal
      littermates for given ages. OPG gene expression was found to be higher in the
      dental follicle of the tl/tl mutants than in normals. Transfecting short
      interfering RNA specific for CSF-1 mRNA into dental follicle cells resulted in an
      up-regulation of OPG expression. Thus, these studies support our hypothesis that
      the down-regulation of OPG needed for tooth eruption is mediated by CSF-1.

PMID- 16109996
TI  - Eugenol inhibits calcium currents in dental afferent neurons.
AB  - Eugenol is a topical analgesic agent widely used in the dental clinic. To
      elucidate the molecular mechanism underlying its analgesic action, we
      investigated the effect of eugenol on high-voltage-activated calcium channel
      (HVACC) currents in dental primary afferent neurons, and with a heterologous
      expression system. Dental primary afferent neurons were identified by retrograde
      labeling with a fluorescent dye, DiI. Eugenol inhibited HVACC currents in both
      capsaicin-sensitive and capsaicin-insensitive dental primary afferent neurons.
      The HVACC inhibition by eugenol was not blocked by capsazepine, a competitive
      transient receptor potential vanilloid 1 (TRPV1) antagonist. Eugenol inhibited N
      type calcium currents in the cell line C2D7, stably expressing the human N-type
      calcium channels, where TRPV1 was not endogenously expressed. Our results suggest
      that the HVACC inhibition by eugenol in dental primary afferent neurons, which is
      not mediated by TRPV1 activation, might contribute to eugenol's analgesic effect.
      ABBREVIATIONS: high-voltage-activated calcium channel, HVACC; transient receptor
      potential vanilloid 1, TRPV1; trigeminal ganglion, TG; dorsal root ganglion, DRG;
      capsazepine, CZP.

PMID- 16109997
TI  - Bupivacaine induces apoptosis via ROS in the Schwann cell line.
AB  - Local anesthetics have been generally accepted as being safe. However, recent
      clinical trials and basic studies have provided strong evidence for the
      neurotoxicity of local anesthetics, especially through apoptosis. We hypothesized
      that local anesthetics cause neural complications through Schwann cell apoptosis.
      Among local anesthetics tested on the Schwann cell line, RT4-D6P2T, bupivacaine
      significantly induced cell death, measured by the methyl tetrazolium (MTT) assay,
      in a dose- (LD50 = 476 microM) and time-dependent manner. The bupivacaine-induced
      generation of reactive oxygen species (ROS), which was initiated within 5 hrs and
      preceded the activation of caspase-3 and poly ADP-ribose polymerase (PARP)
      degradation, was suggested to trigger apoptosis, exhibited by Hoechst 33258
      nuclear staining and DNA fragmentation. Furthermore, concomitant block of ROS by
      anti-oxidants significantly inhibited bupivacaine-induced apoptosis. Among the
      local anesthetics for peripheral neural blocks, bupivacaine induced apoptosis in
      the Schwann cell line, which may be associated with ROS production.

PMID- 16109998
TI  - Dendritic-NK cell interactions in P. gingivalis-specific responses.
AB  - Patients with localized aggressive periodontitis have type-1 cytokines in
      gingival crevicular fluid and high titers of IFN-gamma-dependent IgG2 reactive
      with P. gingivalis in gingival crevicular fluid and serum. Localized aggressive
      periodontitis monocytes spontaneously differentiate into dendritic cells that can
      stimulate IFN-gamma production by NK cells. These relationships prompted the
      hypothesis that P. gingivalis-dendritic cell-NK cell interactions might promote
      type-1 cytokine responses. Although P. gingivalis is not a potent inducer of Th1
      responses, it stimulated strong IL-12 responses by monocyte-derived dendritic
      cells in the presence of IFN-gamma, and IFN-gamma was produced by NK cells within
      24 hrs in the presence of dendritic cells. Anti-P. gingivalis IgG2 responses were
      enhanced by dendritic cells, and removal of NK cells reduced IFN-gamma- and P.
      gingivalis-specific IgG2. Thus, P. gingivalis-dendritic cell-NK cell interactions
      apparently resulted in reciprocal stimulation and increased type-1 cytokine
      production by both dendritic cells and NK cells, and increased P. gingivalis
      specific IgG2.

PMID- 16109999
TI  - Ecteinascidin-743 (ET-743): early test or effective treatment in soft tissue
      sarcomas?

PMID- 16110000
TI  - Quality-of-life assessment in pediatric brain tumor patients and survivors:
      lessons learned and challenges to face.

PMID- 16110001
TI  - Dignity therapy: advancing the science of spiritual care in terminal illness.

PMID- 16110002
TI  - Variation in the choice of breast-conserving surgery or mastectomy: patient or
      physician decision making?

PMID- 16110003
TI  - What is atypical lobular hyperplasia and what does it mean for the patient?

PMID- 16110004
TI  - Testing chemotherapy for breast cancer: timing is everything.

PMID- 16110005
TI  - Predicting the future from trials of the past: epidermal growth factor receptor
      expression and outcome of fractionated radiation therapy trials.

PMID- 16110006
TI  - Screening for familial ovarian cancer: the need for well-designed prospective
      studies.

PMID- 16110007
TI  - Gefitinib in colorectal cancer: if wishes were horses.

PMID- 16110008
TI  - Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft
      tissue sarcomas: multicenter phase II and pharmacokinetic study.
AB  - PURPOSE: To evaluate the response rate, toxicity profile, and pharmacokinetics of
      ecteinascidin-743 (ET-743) as first-line therapy in patients with unresectable
      advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: Thirty-six patients
      with STS were enrolled onto the study between September 1999 and August 2000.
      Patients were treated with 1.5 mg/m2 of ET-743 given as a 24-hour continuous
      intravenous (IV) infusion every 21 days. Pharmacokinetic sampling was performed
      in 23 patients. RESULTS: One complete and five partial responses were achieved in
      35 assessable patients for an overall response rate of 17.1% (95% CI, 6.6% to
      33.6%). In addition, one patient had a minor response, leading to an overall
      clinical benefit of 20%. Neutropenia and transaminitis were the main grade 3 to 4
      toxicities, which occurred in 33% and 36% of the patients. The estimated 1-year
      progression-free and overall survival rates were 21% (95% CI, 11% to 41%) and 72%
      (95% CI, 59% to 88%), respectively. Total body clearance (L/h) was not
      significantly correlated with body-surface area (r = -0.28; P = .21). Mild
      hepatic impairment or the extent of prior cytotoxic therapy does not seem to
      contribute significantly to the high interpatient variability (49%) in the
      clearance of this drug. Severity of treatment-related toxicity was not correlated
      with pharmacokinetic variables. CONCLUSION: ET-743 demonstrates clinical activity
      as first-line therapy against STS with acceptable toxicity. Additional studies to
      establish empirical dosing guidelines may be necessary to improve the safety of
      the drug in patients with varying degrees of hepatic dysfunction and definitively
      establish the role of ET-743 for patients with these malignancies.

PMID- 16110009
TI  - Profile of daily life in children with brain tumors: an assessment of health
      related quality of life.
AB  - PURPOSE: The survival of children with CNS tumors approaches 70%, yet health
      related quality of life (HRQOL) has not been investigated rigorously in this
      population. We aimed to show that universal assessment of HRQOL could be obtained
      easily by using the PedsQL 4.0 and to provide a composite profile of their daily
      lives. PATIENTS AND METHODS: The PedsQL was administered to all patients seen in
      the neuro-oncology clinic at Lucile Packard Children's Hospital (Palo Alto, CA)
      from December 2001, to September 2002. Patients were compared with healthy
      controls by using two-sided t tests to evaluate statistically significant
      differences. RESULTS: One hundred thirty-four patients (73 male; mean age +/-
      standard deviation, 11.8 +/- 5.4 years; 55 had low-grade glioma, 32 had
      medulloblastoma/primitive neuroectodermal tumor/embryonal tumor, 17 had malignant
      astrocytoma, nine had germ-cell tumor, and 21 had other types of tumors) were
      assessed, each in less than 20 minutes. Scores on both child and parent-proxy
      reports for the total HRQOL, psychosocial, physical, emotional, social, and
      school-functioning scales were all significantly lower than controls (P < .01).
      Patients with low-grade glioma were reported to have the highest total HRQOL.
      Children receiving radiation therapy (XRT) but no chemotherapy had significantly
      lower total, psychosocial, emotional, and social functioning than those receiving
      other treatments, including XRT plus chemotherapy. CONCLUSION: The PedsQL can be
      used to assess HRQOL rapidly and easily in children with CNS tumors, who have
      significantly worse HRQOL than healthy children. Children receiving XRT fare
      worse overall; chemotherapy added to XRT does not seem to worsen HRQOL.
      Assessment of HRQOL should be included as an outcome in future clinical trials.

PMID- 16110010
TI  - Prevalence and correlates of fatigue in long-term survivors of childhood
      leukemia.
AB  - PURPOSE: To estimate the prevalence of fatigue, identify the factors associated
      with fatigue, and to explore the relationship between fatigue and quality of life
      (QOL) in long-term survivors of childhood acute lymphoblastic leukemia (ALL).
      METHODS: One hundred sixty-one ALL survivors diagnosed at Childrens Hospital Los
      Angeles (Los Angeles, CA) before age 18 years and between January 1, 1975 and
      December 31, 1995, participated in a structured telephone interview. Participants
      were aged 18 to 41 years and off treatment for an average of 14 years. Four
      measures of fatigue, including the Revised-Piper Fatigue Scale, were used to
      assess fatigue; depression was assessed using the Center for Epidemiological
      Studies Depression Scale. Multivariate logistic regression models were developed
      to identify factors associated with fatigue and depression. RESULTS: Prevalence
      of fatigue (30%) fell within the general population normal limits. Fatigue and
      depression were highly correlated (Pearson r = 0.75). Fatigue was associated with
      marriage (OR = 0.11; 95% CI, 0.02 to 0.50), having children (OR = 5.80; 95% CI,
      1.30 to 25.82), sleep disturbances (OR = 6.15; 95% CI, 2.33 to 16.22), pain (OR =
      5.56; 95% CI, 2.13 to 14.48), obesity (OR = 3.80; 95% CI, 1.41 to 10.26),
      cognitive impairment (OR = 2.56; 95% CI, 1.02 to 6.38), and exercise-induced
      symptoms (OR = 2.98; 95% CI, 1.11 to 8.02). Four factors associated with fatigue
      were also associated with depression: sleep disturbances, pain, obesity, and
      cognitive impairment. Fatigue was inversely related to QOL. CONCLUSION: Some
      survivors of childhood ALL experience fatigue many years after treatment.
      Fatigued survivors represent a high-risk subgroup as they report more depression
      and poorer QOL than non-fatigued survivors and their peers.

PMID- 16110011
TI  - Neurocognitive consequences of risk-adapted therapy for childhood
      medulloblastoma.
AB  - PURPOSE: This prospective, longitudinal study examined the effects of risk
      adapted craniospinal irradiation (CSI) dose and the interactions of dose with age
      and time from diagnosis on intelligence quotient (IQ) and academic achievement
      (reading, spelling, and math) among patients treated for medulloblastoma (MB).
      PATIENTS AND METHODS: Patients received serial neurocognitive testing spanning
      from 0 to 6.03 years after diagnosis (median, 3.14 years). The multi
      institutional study included 111 patients, who were 3 to 20 years of age at
      diagnosis (median age, 7.4 years), treated for MB with risk-adapted CSI followed
      by four cycles of high-dose chemotherapy (cyclophosphamide, cisplatin, and
      vincristine) with stem-cell support. High-risk patients (HR; n = 37) received CSI
      to 36 to 39.6 Gy and conformal boost treatment of the primary site to 55.8 to
      59.4 Gy. Average-risk patients (AR; n = 74) received CSI to 23.4 Gy and conformal
      boost treatment of the posterior fossa to 36.0 Gy and primary site to 55.8 Gy.
      RESULTS: Multivariate modeling revealed statistically significant declines in
      mean IQ (-1.59 points/yr; P = .006), reading (-2.95 points/yr; P < .0001),
      spelling (-2.94 points/yr; P < .0001), and math (-1.87 points/yr; P = .003)
      scores for the entire group. The effects of risk-adapted radiation therapy on IQ,
      reading, and spelling were moderated by age, with the greatest rates of decline
      observed for the HR patients who were younger (< 7 years old) at diagnosis.
      CONCLUSION: Young age at diagnosis was the most prominent risk factor for
      neurocognitive deficits among survivors of MB despite reductions in CSI dosing
      and efforts to limit the boost volume. Younger patients exhibited substantial
      problems with the development of reading skills.

PMID- 16110012
TI  - Dignity therapy: a novel psychotherapeutic intervention for patients near the end
      of life.
AB  - PURPOSE: This study examined a novel intervention, dignity therapy, designed to
      address psychosocial and existential distress among terminally ill patients.
      Dignity therapy invites patients to discuss issues that matter most or that they
      would most want remembered. Sessions are transcribed and edited, with a returned
      final version that they can bequeath to a friend or family member. The objective
      of this study was to establish the feasibility of dignity therapy and determine
      its impact on various measures of psychosocial and existential distress. PATIENTS
      AND METHODS: Terminally ill inpatients and those receiving home-based palliative
      care services in Winnipeg, Canada, and Perth, Australia, were asked to complete
      pre- and post-intervention measures of sense of dignity, depression, suffering,
      and hopelessness; sense of purpose, sense of meaning, desire for death, will to
      live, and suicidality; and a post-intervention satisfaction survey. RESULTS:
      Ninety-one percent of participants reported being satisfied with dignity therapy;
      76% reported a heightened sense of dignity; 68% reported an increased sense of
      purpose; 67% reported a heightened sense of meaning; 47% reported an increased
      will to live; and 81% reported that it had been or would be of help to their
      family. Post-intervention measures of suffering showed significant improvement (P
      = .023) and reduced depressive symptoms (P = .05). Finding dignity therapy
      helpful to their family correlated with life feeling more meaningful (r = 0.480;
      P = .000) and having a sense of purpose (r = 0.562; P = .000), accompanied by a
      lessened sense of suffering (r = 0.327; P = .001) and increased will to live (r =
      0.387; P = .000). CONCLUSION: Dignity therapy shows promise as a novel
      therapeutic intervention for suffering and distress at the end of life.

PMID- 16110013
TI  - Patient involvement in surgery treatment decisions for breast cancer.
AB  - PURPOSE: High rates of mastectomy and marked regional variations have motivated
      lingering concerns about overtreatment and failure to involve women in treatment
      decisions. We examined the relationship between patient involvement in decision
      making and type of surgical treatment for women with breast cancer. METHODS: All
      women with ductal carcinoma-in-situ and a 20% random sample of women with
      invasive breast cancer aged 79 years and younger who were diagnosed in 2002 and
      reported to the Detroit and Los Angeles Surveillance, Epidemiology, and End
      Results registries were identified and surveyed shortly after receipt of surgical
      treatment (response rate, 77.4%; n = 1,844). RESULTS: Mean age was 60.1 years;
      70.2% of the women were white, 18.0% were African American, and 11.8% were from
      other ethnic groups. Overall, 30.2% of women received mastectomy as initial
      treatment. Most women reported that they made the surgical decision (41.0%) or
      that the decision was shared (37.1%); 21.9% of patients reported that their
      surgeon made the decision with or without their input. Among white women, only
      5.3% of patients whose surgeon made the decision received mastectomy compared
      with 16.8% of women who shared the decision and 27.0% of women who made the
      decision (P < .001, adjusted for clinical factors, predisposing factors, and
      number of surgeons visited). However, this association was not observed for
      African American women (Wald test 10.0, P = .041). CONCLUSION: Most women
      reported that they made or shared the decision about surgical treatment. More
      patient involvement in decision making was associated with greater use of
      mastectomy. Racial differences in the association of involvement with receipt of
      treatment suggest that the decision-making process varies by racial groups.

PMID- 16110014
TI  - Bilateral risk for subsequent breast cancer after lobular carcinoma-in-situ:
      analysis of surveillance, epidemiology, and end results data.
AB  - PURPOSE: Noninvasive lesions involving the lobules of the breast are increasingly
      diagnosed as incidental microscopic findings at the time of lumpectomy or core
      needle biopsy. We investigated the incidence rates of invasive breast cancer
      (IBC) after a diagnosis of lobular carcinoma-in-situ (LCIS) by using
      Surveillance, Epidemiology, and End Results (SEER) data. PATIENTS AND METHODS:
      Patients (N = 4,853) having a diagnosis of primary LCIS in the time period of
      1973 to 1998 were identified using the SEER Public Use CD-ROM data. The database
      was then searched for patients with subsequent primary IBC occurrences (n = 350).
      The clinical and pathologic characteristics of patients with subsequent primary
      IBCs were compared with the characteristics of patients with primary IBCs
      attained during the same time period (N = 255,114). RESULTS: The incidence of IBC
      increased over time from diagnosis of LCIS, with 7.1% +/- 0.5% incidence of IBC
      at 10 years. IBCs detected after partial mastectomy occurred in either breast
      (46% ipsilateral and 54% contralateral); however, after mastectomy, most IBCs
      were contralateral (94.7%). IBCs occurring after LCIS more often represented
      invasive lobular histology (23.1%) compared with primary IBCs (6.5%). The
      standardized incidence ratio (the ratio of observed to expected cases) for
      developing IBC was 2.4 (95% CI, 2.1 to 2.6) adjusted for age and year of
      diagnosis. CONCLUSION: LCIS is associated with increased risk of subsequent
      invasive disease, with equal predisposition in either breast. The minimum risk of
      developing IBC after LCIS is 7.1% at 10 years.

PMID- 16110015
TI  - Randomized phase III study of docetaxel compared with paclitaxel in metastatic
      breast cancer.
AB  - PURPOSE: This randomized, controlled, multicenter, open-label, phase III study
      compared docetaxel versus paclitaxel in patients with advanced breast cancer that
      had progressed after an anthracycline-containing chemotherapy regimen. PATIENTS
      AND METHODS: Patients (n = 449) were randomly assigned to receive either
      docetaxel 100 mg/m2 (n = 225) or paclitaxel 175 mg/m2 (n = 224) on day 1, every
      21 days until tumor progression, unacceptable toxicity, or withdrawal of consent.
      RESULTS: In the intent-to-treat population, both the median overall survival (OS,
      15.4 v 12.7 months; hazard ratio [HR], 1.41; 95% CI, 1.15 to 1.73; P = .03) and
      the median time to progression (TTP, 5.7 months v 3.6 months; HR, 1.64; 95% CI,
      1.33 to 2.02; P < .0001) for docetaxel were significantly longer than for
      paclitaxel, and the overall response rate (ORR, 32% v 25%; P = .10) was higher
      for docetaxel. These results were confirmed by multivariate analyses. The
      incidence of treatment-related hematologic and nonhematologic toxicities was
      greater for docetaxel than for paclitaxel; however, quality-of-life scores were
      not statistically different between treatment groups over time. CONCLUSION:
      Docetaxel was superior to paclitaxel in terms of OS and TTP. ORR was higher for
      docetaxel. Hematologic and nonhematologic toxicities occurred more frequently in
      the docetaxel group. The global quality-of-life scores were similar for both
      agents over time.

PMID- 16110016
TI  - Drug-metabolizing enzyme polymorphisms predict clinical outcome in a node
      positive breast cancer cohort.
AB  - PURPOSE: Adjuvant chemotherapy cures only a subset of women with nonmetastatic
      breast cancer. Genotypes in drug-metabolizing enzymes, including functional
      polymorphisms in cytochrome P450 (CYP) and glutathione S-transferases (GST), may
      predict treatment-related outcomes. PATIENTS AND METHODS: We examined CYP3A4*1B,
      CYP3A5*3, and deletions in GST mu (GSTM1) and theta (GSTT1), as well as a priori
      defined combinations of polymorphisms in these genes. Using a cohort of 90 node
      positive breast cancer patients who received anthracycline-based adjuvant
      chemotherapy followed by high-dose multiagent chemotherapy with stem-cell rescue,
      we estimated the effect of genotype and other known prognostic factors on disease
      free survival (DFS) and overall survival (OS). RESULTS: Patients who carried
      homozygous CYP3A4*1B and CYP3A5*3 variants and did not carry homozygous deletions
      in both GSTM1 and GSTT1 (denoted low-drug genotype group) had a 4.9-fold poorer
      DFS (P = .021) and a four-fold poorer OS (P = .031) compared with individuals who
      did not carry any CYP3A4*1B or CYP3A5*3 variants but had deletions in both GSTT1
      and GSTM1 (denoted high-drug genotype group). After adjustment for other
      significant prognostic factors, the low-drug genotype group retained a
      significantly poorer DFS (hazard ratio [HR] = 4.9; 95% CI, 1.7 to 14.6; P = .004)
      and OS (HR = 4.8; 95% CI, 1.8 to 12.9; P = .002) compared with the high- and
      intermediate-drug combined genotype group. In the multivariate model, having low
      drug genotype group status had a greater impact on clinical outcome than estrogen
      receptor status. CONCLUSION: Combined genotypes at CYP3A4, CYP3A5, GSTM1, and
      GSTT1 influence the probability of treatment failure after high-dose adjuvant
      chemotherapy for node-positive breast cancer.

PMID- 16110017
TI  - Epidermal growth factor receptor expression in pretreatment biopsies from head
      and neck squamous cell carcinoma as a predictive factor for a benefit from
      accelerated radiation therapy in a randomized controlled trial.
AB  - PURPOSE: Accelerated repopulation is a main reason for locoregional failure after
      fractionated radiotherapy for head and neck squamous cell carcinoma (HNSCC).
      Epidermal growth factor receptor (EGFR) is a key controller of cellular
      proliferation in HNSCC, which stimulated the current study to look for a direct
      link between EGFR status and a possible clinical advantage of accelerated
      radiotherapy. PATIENTS AND METHODS: Immunohistochemical staining for EGFR was
      performed in 304 patients with available pretreatment tumor biopsy material among
      918 patients randomized to receive continuous hyperfractionated accelerated
      radiotherapy versus conventionally fractionated radiotherapy. The EGFR index was
      estimated as the proportion of tumor cells with EGFR membrane staining. RESULTS:
      Significant benefit in locoregional tumor control from continuous
      hyperfractionated accelerated radiotherapy was seen in patients with HNSCC with
      high EGFR expression (2P = .010) but not in those with low EGFR expression (2P =
      .85). EGFR status had no significant effect on survival or rate of distant
      metastases. The EGFR index was significantly associated with histologic grade and
      microvessel density. There was moderate support for an association between EGFR
      status and subsite within the head and neck region but no significant association
      with Ki-67 index, Ki-67 pattern, p53 index, p53 intensity, bcl-2 expression, or
      cyclin D1 index. CONCLUSION: This study indicates a key role for the EGFR
      receptor in determining the proliferative cellular response to fractionated
      radiotherapy in HNSCC. It also shows that we can select the dose-fractionation
      regime that has the greatest chance of benefiting the patient. These results also
      encourage further development of EGFR targeting combined with fractionated
      radiotherapy in HNSCC.

PMID- 16110018
TI  - Screening for familial ovarian cancer: failure of current protocols to detect
      ovarian cancer at an early stage according to the international Federation of
      gynecology and obstetrics system.
AB  - PURPOSE: To assess the effectiveness of annual ovarian cancer screening
      (transvaginal ultrasound and serum CA-125 estimation) in detecting presymptomatic
      ovarian cancer in women at increased genetic risk. PATIENTS AND METHODS: A cohort
      of 1,110 women at increased risk of ovarian cancer were screened between January
      1991 and March 2004; 553 were moderate-risk individuals (4% to 10% lifetime risk)
      and 557 were high-risk individuals (> 10% lifetime risk). Outcome measurements
      include the number and stage of screen-detected cancers, the number and stage of
      cancers not detected at screening, the number of equivocal screening results
      requiring recall/repetition, and the number of women undergoing surgery for
      benign disease. RESULTS: Thirteen epithelial ovarian malignancies (12 invasive
      and one borderline), developed in the cohort. Ten tumors were detected at
      screening: three International Federation of Gynecology and Obstetrics (FIGO)
      stage I (including borderline), two stage II, four stage III, and one stage IV.
      Of the three cancers not detected by screening, two were stage III and one was
      stage IV; 29 women underwent diagnostic surgery but were found not to have
      ovarian cancer. CONCLUSION: Annual surveillance by transvaginal ultrasound
      scanning and serum CA-125 measurement in women at increased familial risk of
      ovarian cancer is ineffective in detecting tumors at a sufficiently early stage
      to influence prognosis. With a positive predictive value of 17% and a sensitivity
      of less than 50%, the performance of ultrasound does not satisfy the WHO
      screening standards. In addition, the combined protocol has a particularly high
      false-positive rate in premenopausal women, leading to unnecessary surgical
      intervention.

PMID- 16110019
TI  - Multicenter, randomized phase II trial of oral CI-1033 for previously treated
      advanced ovarian cancer.
AB  - PURPOSE: To evaluate the antitumor activity and toxicity of two doses of CI-1033
      in patients with platinum-refractory or recurrent ovarian cancer, and to
      determine baseline expression of epidermal growth factor receptor in tumor cells.
      PATIENTS AND METHODS: This phase II, open-label clinical trial evaluated CI-1033
      in patients with ovarian cancer who failed prior platinum-based therapy. Two oral
      doses of CI-1033 were evaluated--a 50-mg and a 200--mg oral dose administered
      daily for 21 days in a 28-day cycle. Patients were evaluated for tumor response
      and toxicity; in addition, archival baseline tumor samples were analyzed by
      immunohistochemistry for erbB1 to erbB4 status. RESULTS: One hundred five
      eligible patients were treated. Baseline demographic characteristics were
      balanced in this heavily pretreated patient population. The median number of
      prior chemotherapy regimens received was four. The most commonly encountered drug
      related adverse events for both dose arms were gastrointestinal (diarrhea,
      nausea, stomatitis) toxicity, asthenia, and rash. No responses were observed.
      Stable disease was confirmed in 34% and 26% of patients in the 200-mg and 50-mg
      arms, respectively, and 1-year survival rates were 38.5% and 37.7%, respectively.
      Baseline erbB3 and erbB4 revealed the highest frequencies of expression, while
      erbB2 was the lowest. CONCLUSION: CI-1033 did not show activity in unscreened
      patients with advanced ovarian cancer. At 50 mg/d, CI-1033 had a more favorable
      adverse events profile than at 200 mg/d. erbB3 and erbB4 receptors showed the
      highest expression in tumor samples while erbB2 revealed the least. There appears
      to be no association between baseline erbB expression and disease stability.

PMID- 16110020
TI  - Quality-of-life comparisons in a randomized trial of interval secondary
      cytoreduction in advanced ovarian carcinoma: a Gynecologic Oncology Group study.
AB  - PURPOSE: To compare self-reported quality of life (QOL) in patients who did
      versus did not undergo interval secondary cytoreduction after initial surgery and
      combination chemotherapy for advanced ovarian cancer and to assess the
      association between baseline QOL scores and survival. PATIENTS AND METHODS:
      Consenting patients participating in a Gynecologic Oncology Group (GOG) phase III
      treatment trial (GOG 152) completed the Functional Assessment of Cancer Therapy
      Ovarian (FACT-O) questionnaire and treatment-specific supplemental questions at
      the third and sixth chemotherapy cycles and at 6 and 12 months after starting
      treatment. RESULTS: For all patients, QOL decreased approximately 1 unit from the
      first to second assessment. Significant improvement observed at 6 months (P <
      .001) was sustained at 12 months, with no appreciable between-group difference.
      The baseline FACT-O score was associated with overall survival (P = .048) but not
      progression-free survival. Less neurotoxicity was reported among patients who did
      (38.4%) versus did not (54.0%) undergo interval secondary cytoreduction at the
      third assessment (P = .005), and older patients experienced more long-term
      effects. CONCLUSION: This is the first multicenter randomized trial in ovarian
      cancer to longitudinally examine self-reported QOL and establish a predictive
      value of baseline QOL on survival, attributed primarily to the lowest-scoring
      quartile. Although interval secondary cytoreduction resulted in no notable long
      term difference, a clinically significant improvement was seen in both arms at 6
      and 12 months after starting therapy. Interestingly, there were fewer complaints
      of neurotoxicity at 6 months among patients who did versus did not undergo
      interval secondary cytoreduction.

PMID- 16110021
TI  - Phase II study of gefitinib, fluorouracil, leucovorin, and oxaliplatin therapy in
      previously treated patients with metastatic colorectal cancer.
AB  - PURPOSE: To investigate the gefitinib, fluorouracil (FU), leucovorin, and
      oxaliplatin regimen (IFOX) in previously treated patients with metastatic
      colorectal cancer. PATIENTS AND METHODS: Eligible patients had stage IV
      colorectal adenocarcinoma and had demonstrated progression or intolerance to a
      prior chemotherapy regimen not including oxaliplatin. Each cycle consisted of 14
      days. Cycle 1 consisted of oxaliplatin 85 mg/m2 intravenously (IV) during 2 hours
      on day 1, hours 0 to 2; leucovorin 200 mg/m2 IV on days 1 and 2, hours 0 to 2; FU
      400 mg/m2 IV push on days 1 and 2; and FU 600 mg/m2 IV on days 1 and 2, hours 2
      to 24 (FOLFOX-4). All subsequent cycles consisted of FOLFOX-4 with gefitinib at
      500 mg/d administered orally throughout the 14-day cycle. RESULTS: Twenty-seven
      patients were enrolled onto the study. The median number of prior chemotherapy
      regimens was two, and 74% of all patients received prior irinotecan. Nine of the
      27 patients (33%) and six of the 20 patients (30%) who had prior FU and
      irinotecan had a partial response by Response Evaluation Criteria in Solid Tumors
      Group criteria. Median overall survival was 12.0 months. Median event-free
      survival was 5.4 months. Grade 3 to 4 toxicities included neutropenia (48%),
      diarrhea (48%), nausea (22%), and vomiting (15%). CONCLUSION: IFOX is an active
      regimen in patients with previously treated metastatic colorectal adenocarcinoma,
      demonstrating higher response rates than those reported with FOLFOX-4 alone in a
      similar patient population.

PMID- 16110022
TI  - Determination of TP53 mutation is more relevant than microsatellite instability
      status for the prediction of disease-free survival in adjuvant-treated stage III
      colon cancer patients.
AB  - PURPOSE: Microsatellite instability (MSI), TP53 mutation, and KRAS mutation
      status have been reported as prognostic factors in colon cancer. Most studies,
      however, have included heterogeneous groups of patients with respect to cancer
      stage. We determined the prognostic relevance of high-frequency MSI (MSI-H), TP53
      mutations, and KRAS mutations in a well-defined group of patients with stage III
      colon cancer (N = 391), randomly assigned for adjuvant treatment with
      fluorouracil-based chemotherapy. METHODS: Three hundred ninety-one tumor
      specimens were available. MSI was determined in 273 specimens, and mutation
      analyses of TP53 and KRAS were performed in 220 and 205 specimens, respectively.
      RESULTS: In a univariate analysis, MSI-H (44 of 273; 16%) was associated with a
      longer disease-free survival (DFS; P = .038), but in a multivariate model
      adjusting for nodal involvement, histology, invasion, and grade of tumor, the
      association of MSI status with DFS did no longer reach statistical significance,
      though the risk estimate for microsatellite stability versus MSI-H tumors did not
      change much. Mutant TP53, found in 116 (53%) of 220 tumors, was associated with a
      shorter DFS, both in univariate (P = .009) and multivariate analyses (P = .018),
      whereas KRAS mutations (58 of 205; 28%) did not show any prognostic significance.
      CONCLUSION: Both mutant TP53 and MSI-H seem to be prognostic indicators for
      disease-free survival, but only TP53 retains statistical significance after
      adjusting for clinical heterogeneity. Thus, in adjuvantly treated patients with
      stage III colon cancer, presence or absence of a TP53 mutation should be
      considered as a better predictor for DFS than MSI status.

PMID- 16110023
TI  - Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival
      and local recurrence rate.
AB  - PURPOSE: To evaluate the long-term effects on survival and recurrence rates of
      preoperative radiotherapy in the treatment of curatively operated rectal cancer
      patients. PATIENTS AND METHODS: Of 1,168 randomly assigned patients in the
      Swedish Rectal Cancer Trial between 1987 and 1990, 908 had curative surgery; 454
      of these patients had surgery alone, and 454 were administered preoperative
      radiotherapy (25 Gy in 5 days) followed by surgery within 1 week. Follow-up was
      performed by matching against three Swedish nationwide registries (the Swedish
      Cancer Register, the Hospital Discharge Register, and the Cause of Death
      Register). RESULTS: Median follow-up time was 13 years (range, 3 to 15 years).
      The overall survival rate in the irradiated group was 38% v 30% in the
      nonirradiated group (P = .008). The cancer-specific survival rate in the
      irradiated group was 72% v 62% in the nonirradiated group (P = .03), and the
      local recurrence rate was 9% v 26% (P < .001), respectively. The reduction of
      local recurrence rates was observed at all tumor heights, although it was not
      statistically significant for tumors greater than 10 cm from the anal verge.
      CONCLUSION: Preoperative radiotherapy with 25 Gy in 1 week before curative
      surgery for rectal cancer is beneficial for overall and cancer-specific survival
      and local recurrence rates after long-term follow-up.

PMID- 16110024
TI  - Adenomatous polyposis families that screen APC mutation-negative by conventional
      methods are genetically heterogeneous.
AB  - PURPOSE: One third of families with classical adenomatous polyposis (FAP), and a
      majority of those with attenuated FAP (AFAP), remain APC mutation-negative by
      conventional methods. Our purpose was to clarify the genetic basis of polyposis
      and genotype-phenotype correlations in such families. PATIENTS AND METHODS: We
      studied a cohort of 29 adenomatous polyposis families that had screened APC
      mutation-negative by the protein truncation test, heteroduplex analysis, and exon
      specific sequencing. The APC gene was investigated for large genomic
      rearrangements by multiplex ligation-dependent probe amplification (MLPA), and
      for allelic mRNA expression by single nucleotide primer extension (SNuPE). The
      AXIN2 gene was screened for mutations by sequencing. RESULTS: Four families (14%)
      showed a constitutional deletion of the entire APC gene (three families) or a
      single exon (one family). Seven families (24%) revealed reduced or extinct mRNA
      expression from one APC allele in blood, accompanied by loss of heterozygosity in
      the APC region in six (75%) of eight tumors. In 15 families (52%), possible APC
      involvement could be neither confirmed nor excluded. Finally, as detailed
      elsewhere, three families (10%) had germline mutations in genes other than APC,
      AXIN2 in one family, and MYH in two families. CONCLUSION: "APC mutation-negative"
      FAP is genetically heterogeneous, and a combination of MLPA and SNuPE is able to
      link a considerable proportion (38%) to APC. Significant differences were
      observed in clinical manifestations between subgroups, emphasizing the importance
      of accurate genetic and clinical characterization for the proper management of
      such families.

PMID- 16110025
TI  - Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or
      without fluorouracil in patients with untreated, advanced gastric, or
      gastroesophageal adenocarcinoma.
AB  - PURPOSE: The purpose of this study was to define the contribution of docetaxel to
      combination chemotherapy in the outcome of patients with advanced gastric or
      gastroesophageal adenocarcinoma. We compared the overall response rate (ORR) and
      safety of docetaxel plus cisplatin (DC) with DC plus fluorouracil (DCF) to select
      either DC or DCF as the experimental treatment in the ensuing phase III part of
      trial V-325. PATIENTS AND METHODS: In this phase II randomized study, untreated
      patients with confirmed advanced gastric or gastroesophageal adenocarcinoma
      received either DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2 on day 1, and
      fluorouracil 750 mg/m2/d as continuous infusion on days 1 to 5) or DC (docetaxel
      85 mg/m2 and cisplatin 75 mg/m2 on day 1) every 3 weeks. An independent data
      monitoring committee (IDMC) was to select one of the two regimens based primarily
      on ORR and safety profile. RESULTS: Of 158 randomly assigned patients, 155 (DCF,
      n = 79; DC, n = 76) received treatment. The confirmed ORR was 43% for DCF (n =
      79) and 26% for DC (n = 76). Median time to progression was 5.9 months for DCF
      and 5.0 months for DC. Median overall survival time was 9.6 months for DCF and
      10.5 months for DC. The most frequent grade 3 and 4 events per patient included
      neutropenia (DCF = 86%; DC = 87%) and GI (DCF = 56%; DC = 30%). CONCLUSION: Both
      regimens were active, but DCF produced a higher confirmed ORR than DC. Toxicity
      profiles of DCF were considered manageable. The IDMC chose DCF for the phase III
      part of V-325, which compares DCF with cisplatin plus fluorouracil.

PMID- 16110026
TI  - Prognostic value of circulating plasma cells in monoclonal gammopathy of
      undetermined significance.
AB  - PURPOSE: Monoclonal gammopathy of undetermined significance (MGUS) progresses to
      multiple myeloma or another related plasma cell disorder (PCD) at a rate of
      approximately 1% per year. Identification of patients with MGUS at high risk of
      progression will allow development of preventive strategies. We studied the
      prognostic value of circulating plasma cells (PCs) in patients with MGUS to
      predict progression. PATIENTS AND METHODS: Patients were eligible for this
      retrospective analysis if they were seen at the Mayo Clinic between 1984 and
      1997, were diagnosed with MGUS, and had an analysis of the peripheral blood for
      circulating PCs by the slide-based immunofluorescence method. Patients were
      observed for progression to another PCD. RESULTS: Three hundred twenty-five
      patients were eligible and 63 (19%) had circulating PCs. Patients with
      circulating PCs were twice as likely (hazard ratio, 2.1) to experience
      progression to another PCD (most commonly myeloma), compared with those without
      circulating PCs (95% CI, 1.1 to 4.3; P = .03). In patients with circulating PCs,
      the median progression-free survival was 138 months compared with a median not
      yet reached for those without circulating PCs (P = .028). The median overall
      survival also was shorter for those with circulating PCs. Other factors with
      prognostic value were high levels of M protein and non-immunoglobulin G heavy
      chain type. CONCLUSION: The presence of circulating PCs, especially when combined
      with other known prognostic factors such as M protein concentration and
      immunoglobulin isotype, identify a group of individuals with MGUS at higher risk
      of progression to overt multiple myeloma.

PMID- 16110027
TI  - Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic
      stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high
      risk acute myeloid leukemia and myelodysplastic syndrome.
AB  - PURPOSE: To improve the effect of allogeneic stem-cell transplantation by
      sequential use of intensive chemotherapy, reduced-intensity conditioning (RIC),
      and prophylactic donor lymphocyte transfusions (pDLTs) in high-risk acute myeloid
      leukemia (AML) and myelodysplastic syndrome (MDS). PATIENTS AND METHODS: In a
      prospective study of 75 consecutive patients (median age, 52.3 years), high risk
      was defined by progressive or refractory disease (n = 59), second remission after
      early relapse (n = 8), or first remission with poor prognosis based on
      cytogenetics or delayed response to induction therapy (n = 8). Unfavorable
      karyotypes were found in 49% of informative patients, and 68 patients had medical
      contraindications against standard conditioning. Fludarabine (30 mg/m2),
      cytarabine (2 g/m2), and amsacrine (100 mg/m2) for 4 days were used for
      cytoreduction. After 3 days of rest, RIC consisted of 4 Gy total-body
      irradiation, antithymocyte globulin, and 80 to 120 mg/kg cyclophosphamide. Thirty
      one patients had an HLA-identical sibling donor; 44 patients had an unrelated
      and/or HLA-mismatched donor. pDLT was given from day +120 in patients who were
      not receiving immunosuppression and were free of graft-versus-host disease
      (GvHD). RESULTS: Complete remission was induced in 66 patients (88%). With a
      median follow-up of 35.1 months (range, 13.6 to 47.6 months), 2-year overall and
      leukemia-free survival were 42% and 40%, respectively. Outcome of patients with
      refractory disease or with complex cytogenetic aberrations was identical to that
      of better prognostic subgroups. Survival was best in patients who received high
      CD34+ cell numbers, and in patients with limited GvHD. CONCLUSION: Sequential use
      of intensive chemotherapy, RIC transplantation, and pDLT represents a promising
      approach to the treatment of high-risk AML and MDS, particularly in patients with
      most unfavorable prognoses.

PMID- 16110028
TI  - Circulating CD34+, CD133+, and vascular endothelial growth factor receptor 2
      positive endothelial progenitor cells in myelofibrosis with myeloid metaplasia.
AB  - PURPOSE: Endothelial progenitor cells (EPCs) are present in circulation and
      contribute to vasculogenesis in adults. We measured the number of circulating
      EPCs in patients with myelofibrosis with myeloid metaplasia (MMM), and we
      examined the relationship between the number of EPCs and severity of the MMM
      disease process. PATIENTS AND METHODS: The number of EPCs was measured by
      assaying the CD34+CD133+ vascular endothelial growth factor receptor 2 (VEGFR2) 
      positive cell phenotype in 110 MMM patients, 16 patients with other Philadelphia
      negative chronic myeloproliferative disorders (Ph-negative CMPDs), and 14 healthy
      participants. In four MMM patients, the capacity of selected CD34+ cells to form
      endothelial colonies (CFU-End) in vitro was tested. RESULTS: CD34+, CD133+, and
      VEGFR2-positive EPCs were detectable in unselected peripheral-blood cells of
      50.9% MMM patients, 37.5% control patients, and 21% healthy participants.
      Patients with MMM had a median of 0.26% EPCs, significantly higher than that in
      healthy controls (median, 0%) and in patients with other Ph-negative CMPDs
      (median, 0.1%). In 14.5% of MMM patients, the numbers of EPCs were greater than
      the highest value found in patients with other Ph-negative CMPDs. CD34+ selected
      cells produced colony-forming unit-endothelial (CFU-End), which were vascular
      endothelial (VE) -cadherin positive, CD31+, von Willebrand factor positive, and
      CD45-. In MMM patients, the larger the number of EPCs, the smaller the number of
      circulating immature myeloid cells and circulating CD45+CD34+ hematopoietic
      progenitor cells. Increased numbers of EPCs were associated with younger age and
      a diagnosis of prefibrotic MMM. CONCLUSION: Circulating EPCs are elevated in MMM
      patients in the early stage of the disease. Heightened mobilization of EPCs may
      represent an important mechanism for development of neoangiogenesis in MMM.

PMID- 16110029
TI  - Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I
      131 tositumomab for untreated follicular lymphoma.
AB  - PURPOSE: To evaluate the safety and efficacy of a sequential chemotherapy plus
      radioimmunotherapy (RIT) regimen in previously untreated follicular non-Hodgkin's
      lymphoma. PATIENTS AND METHODS: Thirty-five patients received an abbreviated
      course (three cycles) of fludarabine followed 6 to 8 weeks later by tositumomab
      and iodine I 131 tositumomab. RESULTS: After fludarabine, 31 (89%) of 35 patients
      responded, with three (9%) of 31 patients achieving a complete response (CR).
      After the full regimen of fludarabine and iodine I 131 tositumomab, all 35
      patients responded; 30 (86%) of 35 patients achieved CR, and five (14%) of 35
      achieved partial response. After a median follow-up of 58 months, the median
      progression-free survival (PFS) had not been reached (95% CI, 27 months to not
      reached), but it will be at least 48 months. The 5-year estimated PFS rate is
      60%. Baseline Follicular Lymphoma International Prognostic Index (FLIPI) was
      significantly associated (P = .003) with PFS. Five of six patients with more than
      25% bone marrow involvement at baseline achieved adequate bone marrow
      cytoreduction to receive standard-dose iodine I 131 tositumomab. Ten (77%) of 13
      patients with baseline bone marrow Bcl-2 positivity demonstrated molecular
      remissions at month 12. Toxicities were manageable and principally hematologic.
      Two (6%) of 35 patients developed human antimurine antibodies (HAMA) after RIT.
      CONCLUSION: Use of abbreviated fludarabine before iodine I 131 tositumomab can
      reduce bone marrow involvement, when needed, to allow the use of RIT and can
      suppress HAMA responses. This sequential treatment regimen is highly effective as
      front-line therapy for follicular lymphoma, particularly for low- or intermediate
      risk FLIPI patients.

PMID- 16110030
TI  - Prognostic factors and outcome of core binding factor acute myeloid leukemia
      patients with t(8;21) differ from those of patients with inv(16): a Cancer and
      Leukemia Group B study.
AB  - PURPOSE: Because both t(8;21) and inv(16) disrupt core binding factor (CBF) in
      acute myeloid leukemia (AML) and confer relatively favorable prognoses, these
      cytogenetic groups are often treated similarly. Recent studies, however, have
      shown different gene profiling for the two groups, underscoring potential
      biologic differences. Therefore, we sought to determine whether these two
      cytogenetic groups should also be considered separate entities from a clinical
      standpoint. PATIENTS AND METHODS: We analyzed 144 consecutive adults with t(8;21)
      and 168 with inv(16) treated on Cancer and Leukemia Group B front-line studies.
      We compared pretreatment features, probability of achieving complete remission
      (CR), overall survival (OS) and cumulative incidence of relapse (CIR) between the
      two groups. RESULTS: With a median follow-up of 6.4 years, for CBF AML as a
      whole, the CR rate was 88%, 5-year OS was 50% and CIR was 53%. After adjusting
      for covariates, patients with t(8;21) had shorter OS (hazard ratio [HR] = 1.5; P
      = .045) and survival after first relapse (HR = 1.7; P = .009) than patients with
      inv(16). Unexpectedly, race was an important predictor for t(8;21) AML, in that
      nonwhites failed induction more often (odds ratio = 5.7; P = .006) and had
      shorter OS than whites when certain secondary cytogenetic abnormalities were
      present. In patients with t(8;21) younger than 60 years, type of induction also
      correlated with relapse risk. For inv(16) AML, secondary cytogenetic
      abnormalities (especially +22) and male sex predicted better outcome. CONCLUSION:
      When the prognostic impact of race, secondary cytogenetic abnormalities, sex, and
      response to salvage treatment is considered, t(8;21) and inv(16) AMLs seem to be
      distinct clinical entities and should be stratified and reported separately.

PMID- 16110031
TI  - Polymorphisms in inflammation genes and bladder cancer: from initiation to
      recurrence, progression, and survival.
AB  - PURPOSE: Since chronic inflammation contributes to tumorigenesis, we hypothesized
      that the risk and clinical outcome of bladder cancer (BC) might be modulated by
      genetic variations in inflammation genes. METHODS: Using the TaqMan method, we
      genotyped single nucleotide polymorphisms in interleukin (IL) -6 (-174 G-->C), IL
      8 (-251 T-->A), tumor necrosis factor-alpha (TNF-alpha; -308 G-->A), and
      peroxisome proliferator-activated receptor gamma (PPARG; Pro12Ala), and
      determined their associations with BC initiation and clinical outcome. RESULTS:
      We found that the IL-6 variant genotype (C/C) was associated with an increased BC
      risk (OR, 1.77; 95% CI, 1.25 to 2.51). There were joint effects between the
      variant IL-6 genotypes and smoking status, and between the variant genotypes of
      IL-6 and other genes. To assess effect on recurrence, we grouped non-muscle
      invasive BC patients according to intravesical Bacillus Calmette-Guerin (BCG)
      treatment status: no BCG, induction BCG (iBCG), and maintenance BCG (mBCG). In
      the Cox proportional hazards model, the variant IL-6 genotype was associated with
      an increased recurrence risk (hazard ratio [HR], 4.60; 95% CI, 1.24 to 17.09) in
      patients receiving mBCG. The variant PPARG genotype was associated with a reduced
      recurrence risk (HR, 0.41; 95% CI, 0.20 to 0.86) among untreated patients. In
      patients with non-muscle-invasive BC, the variant IL-6 genotype was associated
      with an increased progression risk (HR, 1.88; 95% CI, 0.80 to 4.11). In patients
      with invasive BC, variant IL-6 was associated with improved 5-year overall and
      disease-specific survival (HR, 0.43; 95% CI, 0.19 to 0.94 and HR, 0.39; 95% CI,
      0.15 to 1.00, respectively). CONCLUSION: Inflammation gene polymorphisms are
      associated with modified BC risk, treatment response, and survival.

PMID- 16110032
TI  - Increasing incidence of testicular germ cell tumors among black men in the United
      States.
AB  - PURPOSE: There has been marked disparity in the incidence of testicular germ cell
      tumors (TGCT) among white and black men for a number of decades in the United
      States. Since at least the beginning of the Surveillance, Epidemiology, and End
      Results (SEER) Program in 1973, incidence rates among white men have been five
      times higher than rates among black men. In addition, rates among white men have
      been increasing, whereas rates among black men have remained stable. However, a
      recent examination of ethnic-specific rates suggested that the incidence among
      black men may have begun to change in the 1990s. PATIENTS AND METHODS: TGCT
      incidence data from nine registries of the SEER Program were analyzed for the
      years 1973 to 2001. Trends were examined separately for seminoma and nonseminoma.
      RESULTS: Analyses found that the incidence of TGCT began to increase among black
      men between the 1988 to 1992 and 1993 to 1997 periods. Before that time,
      incidence among black men had decreased by 14.8%. Between 1988 to 1992 and 1998
      to 2001, however, the incidence increased by 100%, with the incidence of seminoma
      increasing twice as much (124.4%) as the incidence of nonseminoma (64.3%). Over
      the 29-year time period, there was no evidence of a change in the proportion of
      tumors diagnosed at earlier stages among black men. In contrast, the proportion
      of tumors diagnosed at localized stages significantly increased among white men.
      CONCLUSION: The incidence of TGCT among black men has increased since 1988 to
      1992. Although the reasons for this increase are unclear, screening and earlier
      diagnosis of TGCT do not seem to be factors.

PMID- 16110033
TI  - Modeling the cost of management options for stage I nonseminomatous germ cell
      tumors: a decision tree analysis.
AB  - PURPOSE: Patients with clinical stage I nonseminomatous germ cell tumors (NSGCTs)
      have been managed with surveillance, chemotherapy, or retroperitoneal
      lymphadenectomy (RPLND) with similar survival outcomes. Cost factors influencing
      the choice of therapy were evaluated using computer-based decision analysis.
      METHODS: A detailed model was developed that integrates projected costs for more
      than 60 possible treatment outcomes. It incorporates primary, adjuvant, and
      salvage chemotherapy, primary and post-chemotherapy RPLND, and both laparoscopic
      and open surgical approaches. Starting values and probabilities were derived from
      a comprehensive meta-analysis of the last 25 years of testes cancer literature.
      Hypothesis testing was performed using sensitivity analysis. RESULTS: The model
      predicts a cost premium for both primary chemotherapy (18.7%) and RPLND (51.7%)
      compared with surveillance. If laparoscopic RPLND was practiced, the cost premium
      for primary surgery (29.1%) approached that of chemotherapy (26.4%). Open RPLND
      was 1.25x as costly as laparoscopic RPLND, primarily because of longer
      hospitalization. The choice of open RPLND yielded a 6.9% cost premium for a
      surveillance program in this model. For such a program, primary chemotherapy
      became cost advantageous when the probability of recurrence during surveillance
      was more than 46%. CONCLUSION: This model allows a variety of treatment cost
      hypotheses to be tested. Primary RPLND is never cost advantageous over
      surveillance or primary chemotherapy. Surgical costs can significantly increase
      the overall cost of a surveillance program. In stage I patients with high-risk
      tumor characteristics, primary chemotherapy may have a cost advantage over
      surveillance.

PMID- 16110034
TI  - Phase II trial of the novel retinoid, bexarotene, and gemcitabine plus
      carboplatin in advanced non-small-cell lung cancer.
AB  - PURPOSE: Platinum-based chemotherapy is the standard treatment for advanced non
      small-cell lung cancer (NSCLC). Unfortunately, a plateau in efficacy with
      currently available agents has been reached. Previous studies of the retinoid,
      bexarotene, a retinoid X receptor-specific ligand, have indicated that it may
      improve outcome in advanced NSCLC. PATIENTS AND METHODS: Patients with previously
      untreated stage IIIB or stage IV disease, a performance status of 0 to 2, and
      adequate organ status were entered. Treatment consisted of up to six cycles of
      carboplatin (area under the curve = 5.0 on day 1) and gemcitabine (1,000 mg/m2 on
      days 1 and 8) administered every 21 days. Bexarotene 400 mg/m2 orally was to be
      administered continuously beginning on day 1 and until progression of disease.
      All patients received atorvastatin 10 mg orally beginning before bexarotene. The
      objective was to demonstrate a 1-year survival rate of more than 50%. RESULTS:
      Forty-eight patients were entered; all were assessable for survival, and 47 were
      assessable for toxicity and response. The therapeutic regimen was well tolerated
      except for hypertriglyceridemia. The median time to progression was 6.7 months,
      and overall median survival was 12.7 months. There was a 25% response rate and a
      1-year survival rate of 53%. These results were compared with the outcome of 33
      patients treated at our institution with two-drug, platinum-based chemotherapy on
      controlled trials with similar entry criteria in the previous 5 years.
      CONCLUSION: Bexarotene can be safely added to platinum-based chemotherapy
      provided that there is aggressive prophylaxis of hypertriglyceridemia. The median
      time to progression and overall survival are promising and warrant further
      evaluation of bexarotene in advanced NSCLC.

PMID- 16110035
TI  - Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin
      biopsies after dendritic cell vaccination correlates with clinical outcome.
AB  - PURPOSE: Tumor-specific immunomonitoring is essential to evaluate the efficacy of
      vaccination against cancer. In this study, we investigated the predictive value
      of the presence or absence of antigen-specific T cells in biopsies from delayed
      type hypersensitivity (DTH) sites. PATIENTS AND METHODS: In our ongoing clinical
      trials, HLA-A2.1+ melanoma patients were vaccinated with mature dendritic cells
      (DC) pulsed with melanoma-associated peptides (gp100 and tyrosinase) and keyhole
      limpet hemocyanin. RESULTS: After intradermal administration of a DTH challenge
      with gp100- and tyrosinase peptide-loaded DC, essentially all patients showed a
      positive induration. In clinically responding patients, T cells specific for the
      antigen preferentially accumulated in the DTH site, as visualized by in situ
      tetramer staining. Furthermore, significant numbers of functional gp100 and
      tyrosinase tetramer-positive T cells could be isolated from these DTH biopsies,
      in accordance with the applied antigen in the DTH challenge. We observed a direct
      correlation between the presence of DC vaccine-related T cells in the DTH
      biopsies of stage IV melanoma patients and a positive clinical outcome (P =
      .0012). CONCLUSION: These findings demonstrate the potency of this novel approach
      in the monitoring of vaccination studies in cancer patients.

PMID- 16110036
TI  - Initial and late resistance to imatinib in advanced gastrointestinal stromal
      tumors are predicted by different prognostic factors: a European Organisation for
      Research and Treatment of Cancer-Italian Sarcoma Group-Australasian
      Gastrointestinal Trials Group study.
AB  - PURPOSE: The aim of this study was to identify factors predicting initial and
      late resistance of GI stromal tumor (GIST) patients to imatinib and to document
      the dose-response relationship in the prognostic subgroups. This study is based
      on the European Organisation for Research and Treatment of Cancer-Italian Sarcoma
      Group-Australasian Gastrointestinal Trials Group randomized trial comparing two
      doses of imatinib in advanced disease. PATIENTS AND METHODS: Initial resistance
      was defined as progression within 3 months of randomization, and late resistance
      was defined as progression beyond 3 months. Investigated cofactors include
      imatinib dose, age, sex, performance status, original disease site, site and size
      of lesions at trial entry, and baseline hematologic and biologic parameters.
      RESULTS: Initial resistance was recorded for 116 (12%) of 934 assessable patients
      and was independently predicted by the presence of lung and absence of liver
      metastases, low hemoglobin level, and high granulocyte count. Among 818 patients
      who were alive and progression free at 3 months, 347 subsequent progressions were
      recorded, and late resistance was independently predicted by high baseline
      granulocyte count, primary tumor outside of the stomach, large tumor size, and
      low initial imatinib dose. The impact of initial dose on late resistance was
      mainly significant in patients with a high baseline granulocyte count (>
      5.10(9)/L) and in patients with tumors of GI origin outside of the stomach and
      small intestine. CONCLUSION: Our study identifies patients for whom initial
      and/or long-term treatment needs to be improved and patients who require a high
      initial dose. Correlation of these results with immunohistochemistry and
      molecular parameters may further help to understand the biologic mechanisms of
      resistance.

PMID- 16110037
TI  - Unusual leukemia presentations. Case 1. Pulmonary chloroma preceded by leukemia
      cutis 7 years earlier.

PMID- 16110038
TI  - Unusual leukemia presentations. Case 2. Granulocytic sarcoma of the colon.

PMID- 16110039
TI  - Unusual leukemia presentations. Case 3. Type I IgGlambda cryoglobulinemia
      associated with chronic lymphocytic leukemia.

PMID- 16110040
TI  - Loss of epidermal growth factor receptor expression in lymph node and liver
      metastases of colon carcinoma.

PMID- 16110041
TI  - Radiotherapeutic prophylaxis of gynecomastia.

PMID- 16110042
TI  - Limitations of single-strand conformation polymorphism analysis as a high
      throughput method for the detection of EGFR mutations in the clinical setting.

PMID- 16110043
TI  - Ewing's sarcoma of the rectum: are four cycles of chemotherapy enough?

PMID- 16110044
TI  - Welcome to the new Journal of Attention Disorders.

PMID- 16110046
TI  - Inhibition, ADHD, and computer games: the inhibitory performance of children with
      ADHD on computerized tasks and games.
AB  - Contrary to empirical reports of inhibitory dysfunction in ADHD, parental reports
      suggest that when playing computer games, the inhibitory abilities of children
      with ADHD are unimpaired. This small-scale preliminary investigation into this
      phenomenon looks at inhibition of an ongoing response and activity exhibited by
      children with ADHD between 6 and 14 years old on two commercially available
      games, on the Conners's Continuous Performance Test II (CPT II), and on a more
      game-like version of the same task that incorporates characteristics commonly
      found in commercially available computer games. The performance of participants
      with ADHD on commercially available games is equivalent to that of typically
      developing participants and is significantly better on the more game-like version
      of the CPT II.

PMID- 16110045
TI  - Investigator ratings of ADHD symptoms during a randomized, placebo-controlled
      trial of atomoxetine: a comparison of parents and teachers as informants.
AB  - This study compared investigator ratings of ADHD symptoms based on interviews
      with parents and teachers during a doubleblind, placebo-controlled study of
      atomoxetine. Investigators completed the ADHD Rating Scale: Investigator (ADHDRS
      I) based on separate semistructured interviews with the primary caretaker and
      teacher of the participant. Interviews were conducted at Visits 2 to 7 during a
      double-blind treatment protocol comparing atomoxetine (N= 10) and placebo (N= 6).
      Both parent and teacher-based ratings were sensitive to change in ADHD symptoms
      with atomoxetine treatment. Parent-based assessment differentiated significantly
      between treatment with atomoxetine and placebo, whereas teacher-based assessment
      was less sensitive to change. Parents and teachers showed good agreement on
      change in ADHDRS-I scores. Investigator ratings based on parent- and teacher
      report were sensitive to change in symptoms of ADHD during treatment with
      atomoxetine. Despite good agreement between parent- and teacher-based ratings of
      symptom change, parent-based ADHD symptom ratings are more sensitive to symptom
      change.

PMID- 16110047
TI  - Validation of three dimensions of childhood psychopathology in young clinic
      referred boys.
AB  - Short measures of child inattention-overactivity (IO), aggression-defiance (AG),
      and anxiety-depression or emotionality (EM) derived through a double validation
      procedure are administered to mothers of 243 clinic-referred suburban New York
      boys between 6 and 10 years of age. Mother-rated IO is uniquely related to poor
      performance on cognitive and achievement tests; observed inattentive,
      hyperactive, and impulsive behaviors in a restricted academic setting; less
      father education and lower family income; and most mother-reported impairments
      and treatment use. Mothers of high-IO boys describe themselves and their sons as
      having similar childhood symptoms. AG is uniquely related to child-reported
      disruptive behavior and sensation seeking, many measures of family conflict and
      negative parenting styles, and mother-reported symptom pervasiveness and number
      of treatments. EM is uniquely related only to poorer cognitive and achievement
      test performance, living with one parent, parents who considered themselves too
      busy, and fewer friends. Each dimension also is associated with parallel teacher
      rated factors.

PMID- 16110048
TI  - Self-report of ADHD symptoms in college students and repetition effects.
AB  - The research in this article focuses on the relation between self-report of
      attention deficit disorder (ADD) symptoms and performance on a two-alternative
      forced-choice task that measures repetition effects. The ADD/Hyperactive
      Adolescent Self-Report Scale--Short Form is administered to college students
      after they completed the repetition effects task. Performance to familiar and
      novel stimuli can be measured using this paradigm. The results indicate that
      participants in the good and poor attention groups do not differ in their
      responses to repeated stimuli. However, participants who self-report poor
      attention are faster to respond to novel stimuli compared with participants who
      self-report good attention. This brief questionnaire appears to capture
      individual differences in attention and may be useful in attention research.

PMID- 16110049
TI  - Use of the Conners-wells adolescent self-report scale (short form) with children.
AB  - The short form of the Conners-Wells Adolescent Self-Report Scale (CASS:Short) is
      administered to 319 children and 844 adolescents to investigate whether the
      instrument can be used with respondents under the age of 12. Mothers of all
      respondents are asked to rate each child using a measure designed to assess a
      parallel set of problem behaviors. The factor structure of the CASS:Short is
      tested in both samples and is found to have good fit to the data. Mean levels of
      ADHD symptomatology are also examined for possible sex and age effects, as was
      the relationship between parent and self-report ratings. The overall results
      provide empirical support for the use of the CASS:Short with children ages 7 to
      11.

PMID- 16110050
TI  - Children with ADHD and depression: a multisource, multimethod assessment of
      clinical, social, and academic functioning.
AB  - Although ADHD and depression are common comorbidities in youth, few studies have
      examined this particular clinical presentation. To address method bias
      limitations of previous research, this study uses multiple informants to compare
      the academic, social, and clinical functioning of children with ADHD, children
      with ADHD and depression, and children without ADHD, all derived from a large
      community sample. High levels of comorbid depression are found in children with
      ADHD. Children withADHDand depression are more depressed and anxious than their
      non-depressed ADHDcounterparts but do not have more extreme levels of ADHD or
      aggression. The association between depression and ADHD does not appear to be
      epiphenomenal, that is, related to a shared association with anxiety or
      externalizing symptoms. Finally, children with ADHD and depression display more
      impairment in social and academic functioning compared to controls. Although
      social impairment is greater in children with ADHD and depression than in
      children with only ADHD, conduct problems are not.

PMID- 16110051
TI  - Applying a psychoeducational perspective to ADHD.
AB  - This article examines whether various cognitive abilities are associated with
      symptoms of ADHD. Cognitive ability is conceptualized using Cattell-Horn-Carroll
      (CHC) theory as measured using the Woodcock-Johnson Tests of Cognitive Ability
      (3rd ed.). This article also examines whether test session behavior mediates the
      association between cognitive ability and ADHD. Participants are children ages 6
      to 12 with (n= 33) and without (n= 19) ADHD. Results show that inattentive
      symptoms of ADHD are significantly related to the CHC ability of processing speed
      above and beyond the effect of test session behavior. Symptoms of ADHD (both
      inattention and hyperactivity/impulsivity) are also significantly associated with
      visual spatial processing, but this is completely mediated by test session
      behavior. It is concluded that inattentive symptoms of ADHD are associated with
      slower processing speed and that this relationship is not explained by test
      session behavior.

PMID- 16110052
TI  - Accuracy of self-evaluation in adults with ADHD: evidence from a driving study.
AB  - Research on children with ADHD indicates an association with inaccuracy of self
      appraisal. This study examines the accuracy of self-evaluations in clinic
      referred adults diagnosed with ADHD. Self-assessments and performance measures of
      driving in naturalistic settings and on a virtual-reality driving simulator are
      used to assess accuracy of self-evaluations. The group diagnosed with ADHD (n=
      44) has a higher rate of collisions, speeding tickets, and total driving
      citations in their driving history; report less use of safe driving behaviors in
      naturalistic settings; and use fewer safe driving behaviors in the simulator than
      the community comparison group (n= 44). Despite poorer performance, adults with
      ADHD provide similar driving self-assessments, thereby overestimating in
      naturalistic settings to a greater degree than the comparison group. These
      findings extend research in children with ADHD to an adult sample in an important
      domain of functioning and may relate to findings of executive deficits associated
      with ADHD.

PMID- 16110053
TI  - H5N1 influenza and the implications for Europe.

PMID- 16110054
TI  - Survival after stroke in south London.

PMID- 16110055
TI  - Cardiac impairment or heart failure?

PMID- 16110056
TI  - Preventing severe infection after splenectomy.

PMID- 16110057
TI  - Medical needs of immigrant populations.

PMID- 16110058
TI  - Disparities in health widen between rich and poor in England.

PMID- 16110059
TI  - US drug industry's guidelines on advertising too limited, say critics.

PMID- 16110060
TI  - Charity challenges US "anti-prostitution" restriction.

PMID- 16110061
TI  - UK government responds to call for change in reproduction technology.

PMID- 16110064
TI  - WHO conference calls for health promotion to be at centre of development.

PMID- 16110065
TI  - Indian Supreme Court ruling makes arrest of doctors harder.

PMID- 16110070
TI  - Aid agencies ignored special needs of elderly people after tsunami.

PMID- 16110071
TI  - Agencies scale up African relief.

PMID- 16110072
TI  - Red eye.

PMID- 16110073
TI  - Should a patient with primary intracerebral haemorrhage receive antiplatelet or
      anticoagulant therapy?

PMID- 16110074
TI  - ABC of asthma. Prevalence.

PMID- 16110075
TI  - Need for differential discounting of costs and health effects in cost
      effectiveness analyses.

PMID- 16110076
TI  - Malpractice in Mexico: arbitration not litigation.

PMID- 16110077
TI  - Prognosis in obesity: obesity in severe mental illness poses particular problems.

PMID- 16110078
TI  - Prognosis in obesity: older people should not be misinformed about being
      overweight.

PMID- 16110079
TI  - Prognosis in obesity: obstacles must be removed to prevent obesity through
      increased physical activity.

PMID- 16110080
TI  - Early life risk factors for obesity in childhood: early feeding is crucial target
      for preventing obesity in children.

PMID- 16110081
TI  - Early life risk factors for obesity in childhood: the hand that rocks the cradle
      rules the world.

PMID- 16110082
TI  - Obesity in middle age and future risk of dementia: dietary fat and sugar may hold
      the clue.

PMID- 16110083
TI  - Obesity in middle age and future risk of dementia: problem is probably greater
      for women.

PMID- 16110084
TI  - Include measurement of waist circumference in GP contract.

PMID- 16110085
TI  - Obesity in middle age and future risk of dementia: midlife obesity increases risk
      of future dementia.

PMID- 16110086
TI  - Audit is important part of drug safety and regulation.

PMID- 16110087
TI  - Dissemination of results needs to be tracked as well as the funding is.

PMID- 16110088
TI  - The sexually dimorphic cephalofoil of bonnethead sharks, Sphyrna tiburo.
AB  - Sexually dimorphic head shape is common in vertebrates from teleosts to mammals.
      Herein we document that cephalic sexual dimorphism is also found in the
      cartilaginous fishes (Chondrichthyes). Male bonnethead sharks develop a prominent
      bulge along the anterior margin of the cephalofoil at the onset of sexual
      maturity. This contrasts with the uniformly rounded anterior margin of adult
      females and juveniles and embryos of both sexes. The anterior cephalic bulge is
      produced by elongation of the rod-like rostral cartilages, and its appearance
      corresponds temporally with the elongation of the rod-like cartilages of the male
      intromittent organs (claspers). We propose that the rostral cartilage elongation
      is a byproduct of endocrinological changes at the onset of sexual maturity that
      stimulate growth of the clasper cartilages. The basal location of the
      chondrichthyan fishes within the vertebrate clade extends the earliest appearance
      of cephalic sexual dimorphism among the vertebrates.

PMID- 16110089
TI  - Sodium nitroprusside potentiates hydrogen-sulfide-induced contractions in body
      wall muscle from a marine worm.
AB  - Hydrogen sulfide (H2S) at concentrations of about 0.05 to 1 mmol.l(-1) appears to
      function as a gasotransmitter in vertebrates, analogous to nitric oxide (NO) and
      carbon monoxide, but the actions of H2S in invertebrate tissue have not been well
      studied. In this study, we investigated the role of H2S in modulating body wall
      muscle tone in the marine echiuran worm Urechis caupo (Echiuridae). We first
      determined that U. caupo body wall homogenates produce H2S upon addition of L
      cysteine and pyridoxal-5'-phosphate (PLP), and that the rate is increased by
      addition of 2-mercaptoethanol, suggesting the presence of an activated L-serine
      sulfhydrase pathway. We then measured the contractile response of U. caupo body
      wall circular muscle strips to sodium hydrosulfide (NaHS)--which produces H2S in
      solution--and the NO donor sodium nitroprusside (SNP), both with and without
      subsequent application of acetylcholine (ACh). We found that NaHS alone
      stimulated contraction in muscle strips equivalent to about one-third the force
      of ACh alone, whereas SNP alone had no effect on muscle tone. However,
      simultaneous addition of NaHS with SNP elicited a much stronger contraction,
      reaching more than twice that of ACh alone, which could be increased further by
      subsequent application of ACh.

PMID- 16110090
TI  - Hydrogen sulfide is synthesized in the gills of the clam Mercenaria mercenaria
      and acts seasonally to modulate branchial muscle contraction.
AB  - Previously we showed that when the gill muscles of the venerid clam Mercenaria
      mercenaria are stimulated to contract by 5-hydroxytryptamine (5HT), the
      contraction is about doubled when another identical dose of 5HT is applied after
      washout. Furthermore, this "endogenous potentiation" is mimicked by nitric oxide
      (NO), which is synthesized in the gill. We now report that the isolated gills
      also synthesize H2S; the basal rate of synthesis was 0.70 micromol.g(-1).h(-1)
      (se = 0.14; n = 24), but in the presence of 5HT (10(-2) M), the rate increased
      markedly to 35.82 micromol.g(-1).h(-1) (se = 4.93; n = 4). In addition,
      dithiothreitol (DTT; 2.2 mM) increased the rate of synthesis significantly to 4.9
      micromol.g(-1).h(-1) (se = 0.8; n = 8). Stimulation of H2S synthesis by 5HT (5 x
      10(-3) M) was seasonal; that is, the rates measured monthly from December through
      June are significantly lower than those measured from July through November. We
      also found that if isolated gills were pretreated with the H2S donor, sodium
      hydrosulfide (NaHS), their contractions in response to 5HT were potentiated. The
      threshold of the potentiation was 10(-8) M NaHS, and the largest effect was at
      10(-6) M. During August, however, when endogenous and NO-induced potentiations
      are both absent, 10(-6) M NaHS was also ineffective. Like the effect of NO, that
      of NaHS (10(-6) M) was blocked by oxadiasoloquinoxalin (ODQ; 5 x 10(-5) M), an
      inhibitor of soluble guanylate cyclase (sGC). Moreover, Rp-8-CPT-cGMPS (10(-5)
      M), which inhibits protein kinase-G, also blocked the effect of NaHS (10(-6) M).
      When isolated gills were treated with 2.2 mM DTT, the endogenous potentiation of
      a second 5HT-induced contraction more than doubled in comparison to untreated
      controls. In conclusion, H2S is synthesized in the gill and, along with NO, is a
      seasonal, endogenous modulator of branchial muscle contraction; its action may be
      mediated through a sGC/cGMP signaling cascade.

PMID- 16110091
TI  - Polar body formation in Spisula oocytes: function of the peripheral aster.
AB  - Activated Spisula oocytes proceed through meiotic stages rapidly and in near
      synchrony, providing an excellent system for analyzing polar body formation. Our
      previous studies suggested that cortical spreading of the metaphase peripheral
      aster determines spatial features of the cortical F-actin ring that is generated
      prior to extrusion of the polar body. We tested this hypothesis by experimentally
      altering the number and cortical contact patterns of peripheral asters. Such
      alteration was achieved by (a) lovastatin-induced arrest at metaphase I, with and
      without hexylene glycol modification, followed by washout; and (b) cytochalasin-D
      inhibition of extrusion of the first polar body, with washout before extrusion of
      the second polar body. Both methods induced simultaneous formation of two or more
      cortically spreading asters, correlated with subsequent formation of double, or
      even triple, overlapping F-actin rings during anaphase. Regardless of pattern,
      ring F-actin was deposited near regions of greatest astral microtubule density,
      indicating that microtubules provided a positive stimulus to which the cortex
      responded indiscriminately. These results strongly support the proposed causal
      relationship between peripheral aster spreading and biogenesis of the F-actin
      ring involved in polar body formation.

PMID- 16110092
TI  - Nutritive phagocyte incubation chambers provide a structural and nutritive
      microenvironment for germ cells of Strongylocentrotus droebachiensis, the green
      sea urchin.
AB  - Here we characterize the germinal epithelia of both sexes of Strongylocentrotus
      droebachiensis, the green sea urchin, throughout its annual gametogenic cycle,
      using light and electron microscopy and cytochemistry. In both sexes, germinal
      epithelia include two interacting cellular populations: nutritive phagocytes
      (NPs) and germ cells. After spring spawning, NPs accumulate nutrients; amitotic
      oogonia and often mitotic spermatogonia occur in clusters beneath NPs; and
      subsequent gametogenic stages are residual or absent. During the summer, NP
      nutrients are mobilized for use in vitellogenesis by residual primary oocytes or
      to support limited spermatogenesis. In addition, some residual primary oocytes
      may degenerate and be phagocytized by NPs. Significant nutrient mobilization from
      NPs and substantial gonial cell mitoses (indicative of new gametogenesis) occur
      in the fall. In both sexes, all of these changes are facilitated by NPs that form
      basal incubation chambers near the gonadal wall and within which germ cells are
      surrounded by nutrients released from the NPs. In females, germ cells at several
      stages of gametogenesis may be housed in separate chambers in the same NP.
      Primary oocytes also carry out jelly coat formation, meiosis, and cortical
      granule translocation within NP incubation chambers. In males, many NPs cooperate
      to provide large continuous chambers that contain spermatogenic cells at diverse
      stages. In both sexes these chambers persist throughout the year and isolate
      gametogenesis from the gonadal lumen. NPs become slender and shorten as their
      nutrients are depleted. Ova or spermatozoa are stored in the gonadal lumen. Post
      spawning, NPs phagocytize differentiated germ cells while simultaneously
      enclosing intact gonial and residual gametogenic cells in basal chambers near the
      gonadal wall. In light of our observations, we suggest investigating proteins
      that may be important in the structural, phagocytic, and nutritive functions of
      NPs and for which corresponding genes have already been identified in the genome
      of S. purpuratus, the closely related purple sea urchin.

PMID- 16110093
TI  - Myelin tetraspan family proteins but no non-tetraspan family proteins are present
      in the ascidian (Ciona intestinalis) genome.
AB  - Several of the proteins used to form and maintain myelin sheaths in the central
      nervous system (CNS) and the peripheral nervous system (PNS) are shared among
      different vertebrate classes. These proteins include one-to-several alternatively
      spliced myelin basic protein (MBP) isoforms in all sheaths, proteolipid protein
      (PLP) and DM20 (except in amphibians) in tetrapod CNS sheaths, and one or two
      protein zero (P0) isoforms in fish CNS and in all vertebrate PNS sheaths. Several
      other proteins, including 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP),
      myelin and lymphocyte protein (MAL), plasmolipin, and peripheral myelin protein
      22 (PMP22; prominent in PNS myelin), are localized to myelin and myelin
      associated membranes, though class distributions are less well studied. Databases
      with known and identified sequences of these proteins from cartilaginous and
      teleost fishes, amphibians, reptiles, birds, and mammals were prepared and used
      to search for potential homologs in the basal vertebrate, Ciona intestinalis.
      Homologs of lipophilin proteins, MAL/plasmolipin, and PMP22 were identified in
      the Ciona genome. In contrast, no MBP, P0, or CNP homologs were found. These
      studies provide a framework for understanding how myelin proteins were recruited
      during evolution and how structural adaptations enabled them to play key roles in
      myelination.

PMID- 16110094
TI  - Pharmacological manipulation of serotonin levels in the nervous system of the
      opisthobranch mollusc Tritonia diomedea.
AB  - Serotonin-related disorders can be treated by manipulating serotonin synthesis
      with the serotonin precursor 5-hydroxytryptophan (5-HTP) or other pharmacological
      agents. The mollusc Tritonia diomedea is a model for investigating the effects of
      altering serotonin content on the functions of identified neurons. We used high
      performance liquid chromatography and immunohistochemistry to examine the amount
      and localization of 5-HTP, serotonin, and the serotonin breakdown product 5
      hydroxyindolacetic acid (5-HIAA) in the Tritonia brain after various
      pharmacological treatments. Exposure to 5-HTP (2 mM for 30 min-1 h) caused an
      immediate and massive increase in total 5-HTP content, which lasted more than 20
      h, and the widespread appearance of 5-HTP immunoreactivity in neurons. Serotonin
      levels rose gradually, but only a restricted number of additional neurons
      displayed serotonin immunoreactivity. 5-HTP treatment also caused an increase in
      the total amount of 5-HIAA and the appearance of 5-HIAA immunoreactivity
      throughout the brain. Treatment with the synthesis cofactor tetrahydrobiopterin,
      the initial precursor tryptophan, or serotonin itself had no persistent effect on
      total serotonin content. The amino acid decarboxylase inhibitor
      hydroxybenzylhydrazine (NSD-1015) also had no effect on the total serotonin
      content, although it caused an accumulation of 5-HTP. Thus, serotonin levels in
      the brain of T. diomedea appear to be maintained by a homeostatic mechanism that
      can be disrupted by 5-HTP.

PMID- 16110095
TI  - Temperature compensation in the escape response of a marine copepod, Calanus
      finmarchicus (Crustacea).
AB  - Calanus finmarchicus, the dominant mesozooplankter of the North Atlantic, is an
      important food source for many fishes and other planktivores. This species, which
      has limited diel vertical migration, depends on its fast-start escape response to
      evade predators. It has myelinated neuronal axons, which contribute to its rapid
      and powerful escape response. The thermal environment that C. finmarchicus
      inhabits ranges from below 0 degrees C to 16 degrees C. Previous studies have
      shown that respiration, growth, and reproductive rates are strongly dependent on
      temperature, with Q10 > 2.5. A comparable dependence of the escape response could
      place the animal at higher risk for cold-compensated predators. Our work focused
      on the temperature dependence of the behavioral response to stimuli that mimic
      predatory attacks. We found that in contrast to other biological processes, all
      aspects of the escape response showed a low dependence on temperature, with Q10
      values below 2. This low temperature dependence was consistent for escape
      parameters that involved neural as well as muscle components of the behavioral
      response. These findings are discussed in the contexts of the predator-prey
      relations of copepods and the thermal dependence of behavior in other taxa.

PMID- 16110096
TI  - Local tumour control in women with carcinoma of the cervix treated with the
      addition of nitroimidazole agents to radiotherapy: a meta-analysis.
AB  - The purpose of this paper was to estimate the effect of nitroimidazoles on the
      local control and overall survival of women receiving radiotherapy for carcinoma
      of the cervix. Sources searched included Medline, Cancerlit and national cancer
      organizations. Proceedings of meetings were hand-searched. Trial selection and
      quality score were performed in duplicate. Data extraction was performed by a
      single author. Five trials involving 849 patients were included. Median follow-up
      was typically 4 years or greater. The odds ratio (OR) for local recurrence did
      not demonstrate a significant effect (OR: 1.14; 95% confidence interval (CI):
      0.78-1.66). The difference in mortality was also non-significant (OR: 1.26; 95%
      CI: 0.95-1.66). A significant increase in neuropathy was found (OR: 3.21; 95% CI:
      1.36-7.55). Subgroup analysis did not reveal any sources of heterogeneity between
      trials. Despite five published randomized trials, evidence supporting the use of
      nitroimidazoles in the treatment of cervical cancer is lacking. Meta-analysis
      revealed no significant effect on local tumour control with a weak, non
      significant trend suggesting a decrease in overall survival. There is, however, a
      significant increase in the rate of neurotoxicity with the use of these
      compounds. This overview can not support the use of these agents.

PMID- 16110097
TI  - Rhodococcus equi pneumonia in AIDS: high-resolution CT findings in five patients.
AB  - The aim of this study was to describe the high-resolution CT scan findings in
      five patients with AIDS and pulmonary infection due to Rhodococcus equi. The
      study included five patients with AIDS and proven R. equi infection. The CT scans
      were reviewed by two observers. The patients included four men and one woman
      ranging from 39 years to 49 years in age (mean 42 years). The findings included
      areas of consolidation (n=5) with single (n=1) or multiple cavitation (n=4),
      ground-glass opacities (n=5), centrilobular nodules (n=3), small centrilobular
      nodular opacities (n=3) and "tree in bud" opacities (n=3). None of the patients
      had pleural effusion or lymph node enlargement. The most common high-resolution
      CT manifestations of R. equi infection consist of areas of consolidation with
      cavitation, ground-glass opacities, nodules and a tree-in-bud pattern.

PMID- 16110098
TI  - CT assessment of tracheal carinal angle and its determinants.
AB  - The aim of this study was to investigate the effect of body habitus, dimensions
      of the thoracic cavity, location of the carina within the mediastinum, and left
      atrial size on tracheal carinal angle using CT scan. The study population was
      drawn from the patients referred to CT scan for various indications. A total of
      120 patients (65 men and 55 women; age range 17-85 years; mean age 56 years) who
      denied a history of prior thoracic surgery, and in whom CT scan excluded
      pulmonary fibrosis, moderate or severe emphysema, atelectasis, intrathoracic mass
      or adenopathy, pericardial or pleural effusion were prospectively enrolled. The
      interbronchial (IBA) and subcarinal (SCA) angles were measured on coronal
      reformatted images. The presternal and retrovertebral fat thickness, the
      anteroposterior and transverse diameters of the thorax, the distances from carina
      to the sternum and to the vertebral column were obtained at the level of carina.
      Three orthogonal dimensions and the volume of the left atrium were also assessed.
      The mean interbronchial angle was 77 degrees +/-13 degrees (range 49-109 degrees
      ) and subcarinal angle was 73 degrees +/-16 degrees (range 34-107 degrees ). IBA
      positively correlated with the female gender (r=0.25, p=0.007), body mass index
      (r=0.28, p=0.002), presternal (r=0.40, p=0.001) and retrovertebral fat thickness
      (r=0.31, p=0.001). The interbronchial angle was significantly greater in obese
      patients compared with lean patients (p=0.02). Both IBA and SCA were positively
      correlated with the left atrial volume (r=0.40, p=0.001 and r=0.34, p=0.001,
      respectively), and its transverse and craniocaudal dimensions. The carina
      vertebral column distance inversely correlated with IBA (r=-0.42, p=0.001) and
      SCA (r=-0.41, p=0.001). The size of the thoracic cavity did not show significant
      relation to tracheal bifurcation angle. Tracheal bifurcation angle ranges widely
      in normal subjects, and absolute measurements of the carinal angle is of little
      diagnostic value. In addition to left atrial enlargement, female gender, obesity
      and close situs of carina relative to vertebral column are associated with
      greater tracheal bifurcation angle.

PMID- 16110099
TI  - 16 detector multislice CT versus skeletal scintigraphy in the diagnosis of wrist
      fractures: value of quantification of 99Tcm-MDP uptake.
AB  - To compare the measured uptake of 99Tcm-methylene diphosphonate (99Tcm-MDP) in
      those scaphoid fractures seen on both 16 detector multislice CT and scintigraphy,
      with those seen only on scintigraphy. Over a 12 month period a total of 51
      patients with suspected fracture underwent both conventional 99Tcm-MDP
      scintigraphy and 16 detector multislice CT on the same day. The 99Tcm-MDP uptake
      was then quantified in patients with identified fracture. This was measured by
      placing a region of interest (ROI) over the fracture site and the mean and
      maximum number of counts were compared with those in a similar size ROI placed
      over background bone activity. A total of 23 fractures were identified on
      scintigraphy of which 16 were also detected on CT (concordant). In seven cases
      the fracture was not seen on CT, even in retrospect (discordant). In the
      discordant cases, follow-up radiographs and MRI (where available) also failed to
      demonstrate a fracture. The mean fracture count to background bone activity ratio
      averaged 7.7 (range 3.2-18.5) for concordant fractures and 3.8 (range 1.7-5.3)
      for discordant fractures (t-test p=0.04). The maximum fracture count to
      background bone activity ratio averaged 12.7 (range 4.3-27.7) for concordant
      fractures and 6.3 (range 2.6-9.5) for discordant fractures (t-test p=0.03). It is
      speculated whether these discordant fractures with less 99Tcm-MDP uptake may
      represent a less severe injury such as bone bruise.

PMID- 16110100
TI  - Congenital internal hernia as a cause of small bowel obstruction: CT findings in
      11 adult patients.
AB  - The aim of this study is to report the CT findings in patients proved to have
      congenital internal hernia (CIH) as a cause of small bowel obstruction (SBO). The
      CT scans of 11 patients (9 men and 2 women, with ages ranging from 20 years to 95
      years (mean 60.7 years), presenting with clinical symptoms and signs of SBO
      without previous abdominal surgery or trauma, were retrospectively reviewed. In
      all patients features of SBO were seen. In addition, in nine of them a saclike
      mass, containing dilated small bowel loops with mesenteric vessels converging
      toward its orifice was demonstrated and a pre-operative diagnosis of an
      incarcerated internal hernia was suggested. In the other two, a closed loop
      obstruction was seen without an identifiable cause. Mural thickening of the
      entrapped loops within the hernial sac was seen in five patients, with
      hypoperfusion in four of them, blurring of the mesenteric vessels with localized
      mesenteric fluid was demonstrated in seven and free peritoneal fluid in 10. All
      patients were operated on following the CT and an incarcerated CIH was confirmed.
      Gangrenous bowel was present at exploration in seven cases. One patient died. In
      conclusion, in patients with intact abdomen and SBO, CT may be the first imaging
      modality to discover a clinically unsuspected CIH, which requires prompt surgical
      intervention. Radiologists should be aware of the CT features suggestive of a SBO
      caused by CIH, i.e. a saclike mass of dilated small bowel loops, as a correct
      diagnosis will influence patient management and prognosis.

PMID- 16110101
TI  - Skin dose alarm levels in cardiac angiography procedures: is a single DAP value
      sufficient?
AB  - Maximum estimated skin doses to patients undergoing coronary angiography
      procedures were obtained using radiographic slow film and diode dosemeters.
      Conversion factors of maximum entrance skin dose versus dose-area product
      (MESD/DAP) for diagnostic (coronary angiography (CA); 20 patients; 2 operators)
      and interventional procedures (percutaneous transluminal coronary angiography
      (PTCA); 10 patients; 1 operator) were 4.3 (mean value of 10 CA; operator A), 3.5
      (mean value of 10 CA; operator B) and 9.7 (mean value of 10 PTCA; operator B)
      mGy(Gycm2)(-1), respectively. The results emphasise a need for both operator- and
      procedure-specific conversion factors. Compared with a single, global factor for
      all cardiac procedures and/or operators that is commonly applied today, such a
      refinement is expected to improve the accuracy in skin dose estimations from
      these procedures. Consequently, reference DAP values used in the clinic to define
      patients who could suffer from a radiation induced skin injury following a
      cardiac procedure, should be defined for each operator/procedure. The film
      technique was found to be superior to the diode in defining conversion factors in
      this study, and allowed for a rapid and accurate estimation of MESD for each
      patient. With appropriate positioning of the diode, a combined film/diode
      technique has a potential use in the training of new angiography operators. The
      patient body mass index (BMI) value was a good indicator of the variation in
      average lung dose (critical organ) between patients. The highest lung dose/DAP
      value was obtained for normal sized patients (BMI: 19-26), and was close to 1.5
      mGy(Gycm2)(-1) with both CA and PTCA procedures.

PMID- 16110102
TI  - The effect of source to image-receptor distance on effective dose for some common
      X-ray projections.
AB  - A number of studies on the effects of source to image distance (SID) on dose to
      the patient have been published. These generally assume that the X-ray beam is
      collimated to a rectangular region of fixed size at the entrance surface of the
      patient at each SID. This is poor radiographic practice. In this work, effective
      doses have been determined using the commercially available Monte Carlo
      simulation package PCXMC. Three collimation cases were considered, namely to
      regions of clinical interest at the entrance and at the centre of the patient,
      and a fixed beam size at the image receptor. For cases of collimation to a
      central region of interest or to the image receptor, the saving in effective dose
      at increased SIDs is modest.

PMID- 16110103
TI  - Breast dose from magnification films in mammography.
AB  - In mammography, much attention has been given to estimating breast dose from
      exposures made in conventional "contact" geometry, but much less attention has
      been given to doses from magnification geometry. Estimation based on contact film
      dose is difficult because the grid is removed, the geometry is different, and
      calculation of scatter reaching the film is complex. In this paper, exposures of
      Perspex blocks of standard thickness to give the same film density in both
      geometries are compared on 20 X-ray sets of various designs with a nominal
      magnification 1.8. The ratio derived between doses in each geometry is 2.2+/
      0.15, giving an average magnification film dose of 5.0+/-0.3 mGy.

PMID- 16110104
TI  - Treatment results and prognostic analysis of radical radiotherapy for locally
      advanced cancer of the uterine cervix.
AB  - This study investigated treatment results and prognostic factors in radical
      radiotherapy for stage IIB-IVA cervical cancer. This is a retrospective analysis
      of 71 patients with cancer of the uterine cervix treated radically with external
      beam radiotherapy and high-dose-rate intracavitary brachytherapy between June
      1991 and May 2004. In 47/71 (66%) of patients' chemotherapy was combined with
      radiotherapy. All 71 patients were retrospectively analysed. The median follow-up
      time was 34.8 months. The median age was 57 years (range 26-78 years) There were
      21 patients (30%) in stage IIB, 3 (4%) stage IIIA, 40 (56%) stage IIIB, and 7
      (10%) stage IVA. The 5-year overall survival rate was 83.5%, 77.0%, and 42.9% for
      stage IIB, III, and IVA, respectively. Federation Internationale de Gynocologie
      et d'Obstetrique (FIGO) classification stage and pelvic and para-aortic nodal
      status significantly affected survival in univariate analysis, but no treatment
      related factor was found to be significant in multivariate analysis. In this
      study para-aortic nodal status was the most important prognostic factor in the
      radical radiotherapy of cervical cancer.

PMID- 16110105
TI  - A phase I trial of stereotactic external beam radiation for subfoveal choroidal
      neovascular membranes in age-related macular degeneration.
AB  - Effective treatment for neovascular age-related macular degeneration (AMD) is
      currently limited. Radiation therapy, a therapeutic approach with known
      antiangiogenic properties, has been investigated as a modality to prevent severe
      visual loss in AMD. Most of the studies using external beam radiation employed
      <25 Gy to the whole eye, which is below the dose of radiation that is toxic to
      the retina and optic nerve ( approximately 50 Gy and approximately 59 Gy,
      respectively). Stereotactic fractionated external beam radiation (St-EBR) is a
      method that allows radiation to be delivered to a small, defined area. We
      investigated the effects of St-EBR in incremental doses up to 40 Gy on
      neovascular AMD. Patients with clinical signs and fluorescein angiography
      demonstrating neovascular AMD, visual acuity (VA) better than 20/400 and
      ineligible for laser treatment (MPS criteria) or who refused to have laser
      photocoagulation were enrolled in the study. Each patient was treated with
      radiation at incremental dosages from 20 Gy to 40 Gy. After completion of the
      radiation course, all patients were followed-up at 3 and 7 weeks and 3, 6, and 12
      months. Best-corrected VA (ETDRS), slit-lamp and fluorescein angiographic
      evaluations were performed at each visit. 94 eyes of 89 patients were treated
      from October 1997 to April 2000. The VA was 0.82+/-0.35 before treatment, 0.83+/
      0.36 at 6 months, and 0.89+/-0.33 at 12 months. No patients suffered any
      significant acute side effects. No significant benefits in either VA or in
      membrane size were derived from increasing the doses of radiation. Our results
      are consistent with trends of a palliative benefit of radiotherapy in neovascular
      AMD and support further investigation of radiotherapy. Since there is no evidence
      that therapeutic effectiveness is dose dependent, our data provide no
      justification for potentially dangerous escalations in radiation dosage for
      treating neovascular AMD.

PMID- 16110106
TI  - Modelling the expected increase in demand for particle radiotherapy: implications
      for the UK.
AB  - The present rapid worldwide expansion of particle radiotherapy services will
      inevitably have an impact on clinical practice within the UK. The most recent
      results of developmental trials using protons and carbon ions are impressive,
      with high cure rates and little or no functional normal tissue changes and a very
      low level of serious treatment-related morbidity. The potential numbers of
      patients that will demand or are referred for treatment abroad are estimated,
      assuming different rates of change and treatment capacities with time. Even if
      the maximum demand were to be under 10% of all patients presently treated by
      radiotherapy, significant numbers (amounting to several thousand patients per
      year) may be advised to seek treatment abroad between 5 and 10 years from now.
      The gap between overall demand and the estimated numbers could be partly,
      although substantially, filled by the establishment of a single large UK
      facility. Should demand increase beyond the estimated level, for example due to
      improved screening of cancer, then a network of UK particle radiotherapy centres
      will be required.

PMID- 16110107
TI  - Quantitative analysis of lung and tumour mobility: comparison of two time
      resolved MRI sequences.
AB  - The purpose of this study was to describe the use of parallel imaging technique
      (PAT) using dynamic MRI in lung and tumour mobility during the breathing cycle.
      20 patients with stage I non-small cell lung carcinoma were investigated using
      two dynamic gradient echo sequences with PAT (TrueFISP (fast imaging with steady
      precession), and fast low angle shot (FLASH). Craniocaudal distance from the apex
      to the diaphragm of the thorax and tumour mobility during the breathing cycle
      were measured. Signal-to-noise ratio (SNR) of the tumour was determined. In spite
      of the different temporal resolutions both trueFISP and FLASH sequence proved to
      be adequate to continuously measure lung motion and tumour mobility. SNR of the
      tumour was significantly higher using the trueFISP sequence than FLASH sequence
      (20.7+/-3.6 vs 5.8+/-2.3, p<0.01). Mobility of the tumour bearing hemithorax was
      significantly lower compared with the non-tumour bearing hemithorax (p<0.05).
      Dynamic MRI using PAT allows for continuous quantitative documentation of tumour
      mobility and lung motion. Because of the higher SNR, trueFISP sequence provides a
      better delineation of intrapulmonary lesions with a sufficient temporal
      resolution.

PMID- 16110108
TI  - Hepatocellular carcinoma tumour thrombus in a re-canalised para-umbilical vein:
      detection by 18-fluoro-2-deoxyglucose positron emission tomography imaging.
AB  - This case report describes an unusual site of tumour thrombus in a re-canalised
      para-umbilical vein, in a patient with hepatocellular carcinoma (HCC) and
      cirrhosis. The tumour thrombus was suspected on conventional radiography and
      confirmed using PET imaging, illustrating the complimentary value of structural
      and functional imaging in achieving the correct diagnosis.

PMID- 16110109
TI  - Rosai-Dorfman disease: unusual cause of diffuse and massive retroperitoneal
      lymphadenopathy.
AB  - Rosai-Dorfman disease (RDD), originally described as sinus histiocytosis with
      massive lymphadenopathy, is a rare histiocytic proliferative disorder with a
      distinctive microscopic appearance. Patients usually present with massive
      cervical lymphadenopathy. However other nodal sites (mediastinal and inguinal)
      are also frequently involved. The retro-peritoneum is an infrequent site of
      involvement. This uncommon entity should also be included in the list of
      differential diagnoses of diffuse and massive lymphadenopathy, which includes
      includes infectious/granulomatous conditions, lymphomatous and metastatic
      disease.

PMID- 16110110
TI  - An unusual case of ureteric obstruction.
AB  - We report a case of a 33-year-old female presenting with right sided abdominal
      pain, a right iliac fossa mass and right hydronephrosis. The mass was
      subsequently shown to represent an isolated desmoid tumour compromising the
      adjacent ureter. The patient had no predisposing factors for this pathology. This
      is an uncommon occurrence and we discuss the imaging features and differential
      diagnosis.

PMID- 16110111
TI  - Intrathoracic gossypiboma: radiographic and CT findings.
AB  - Intrathoracic gossypiboma, a retained surgical sponge in the thoracic cavity, is
      a rare but serious consequence following surgery. Because of its rare occurrence
      and non-specific clinical and radiographic presentations, the diagnosis is often
      missed. Herein we report a patient presenting with a chronic recurrent cough due
      to a retained surgical sponge in the pleural cavity. The patient has been
      misdiagnosed with bronchiectasis for 22 years. The characteristic spongiform
      appearance on CT and a history of previous thoracic surgery led to the diagnosis
      of a gossypiboma that was confirmed at surgery.

PMID- 16110112
TI  - Spontaneous healing of chyle leakage after lymphangiography.
AB  - We report a 34-year-old man with the complication of chylous ascites after
      retroperitoneal lymphadenectomy that was refractory to various conservative
      therapies. Because surgical treatment for chylous ascites was considered,
      lymphangiography was performed to identify the area of leakage of chyle, after
      which the chylous ascites spontaneously healed.

PMID- 16110113
TI  - Incidental localized (solitary) mediastinal malignant mesothelioma.
AB  - Primary mediastinal mesotheliomas are rare tumours. The mesothelial lining cells
      of the the pericardium are suggested as the most probable cells of origin. Most
      of these tumours appear either as a diffuse or nodular thickening of the
      pericardium that encase and even invade the heart. Localized mediastinal
      mesotheliomas are distinctly uncommon. We report the imaging findings of a
      solitary malignant mediastinal mesothelioma that presented mainly as a cystic
      anterior mediastinal mass. On chest radiography, the tumour appeared as a right
      paramediastinal soft tissue mass located adjacent to the right middle and lower
      lobes. On CT, a large, well-circumscribed, right anterior mediastinal mass with a
      central zone of fluid attenuation was observed. This mass had a thin, smooth wall
      of uniform thickness as well as a small component that demonstrated soft tissue
      attenuation. There was no plane of separation between the tumour and
      aorta/superior vena cava. At surgery the tumour could be dissected easily free
      from the pericardium and great vessels and it was removed totally.
      Histopathological examination of the tumour revealed a malignant epitheloid
      mesothelioma.

PMID- 16110114
TI  - CT halo sign: the spectrum of pulmonary diseases.
AB  - The CT halo sign indicates ground glass attenuation surrounding a pulmonary
      nodule on CT. Although it was initially proposed as an early, specific finding of
      invasive pulmonary aspergillosis, it can be caused by many other pathological
      conditions such as infection, neoplastic and inflammatory diseases. The halo of
      ground glass attenuation pathologically represents pulmonary haemorrhage, tumour
      infiltration, or non-haemorrhagic inflammatory processes. Although non-specific,
      this sign is important because the clinical setting and associated radiological
      features may give a clue to the differential diagnosis. In this review, we
      demonstrate the spectrum of pulmonary diseases showing the "CT halo sign" on thin
      section CT and discuss their radiological and clinical features.

PMID- 16110115
TI  - Radiation dose measurement and optimization.

PMID- 16110116
TI  - A 7-year-old female with hypotonia and atakia.

PMID- 16110117
TI  - The outcome of laparoscopic gastrojejunostomy in malignant gastric outlet
      obstruction.
AB  - BACKGROUND AND AIMS: The development of gastric outlet obstruction (GOO) in
      patients with advanced pancreatic cancer is regarded by some as a terminal event.
      There are several interventional options available, one of which is laparoscopic
      gastrojejunostomy (LGJ). To date, there are little data on the effectiveness of
      this intervention. Using patient records we sought to analyze our own experience
      of LGJ in patients with terminal pancreatic cancer. METHODS: A retrospective
      analysis of all patients with pancreatic or peri-ampullary cancer that underwent
      LGJ for GOO. All LGJ were performed by two consultant surgeons at Glasgow Royal
      Infirmary. Patient notes were assessed for survival time after LGJ; post
      operative complications; resumption of oral intake; time to discharge and
      recurrence of GOO after surgery. RESULTS: A total of 18 patients underwent LGJ
      for GOO between 2000 and 2004. Median age at time of procedure was 66.5 yr (range
      40 to 79). Two patients were converted to an open procedure for technical
      reasons, both of whom died in the post-operative period. Of the remaining 16, 15
      had successful relief of GOO. The remaining patient underwent revisional open
      surgery 15 d post-operatively due to persistent GOO. Two patients died in
      hospital but 14 were discharged with symptom relief. Median survival for these
      patients was 59 d (range 12 to 248). CONCLUSION: The development of GOO in
      pancreatic and peri-ampullary cancer should not be regarded as a terminal event.
      LGJ should be considered as a treatment option in these patients.

PMID- 16110118
TI  - Expression of intestinal trefoil factor (TFF-3) in hepatocellular carcinoma.
AB  - BACKGROUND: Trefoil peptides (TFF-1, 2, 3) are a family of protease-resistant
      regulatory factors that play a role in mucosal restitution, angiogenesis,
      apoptosis, and tumor progression. Intestinal trefoil peptide (TFF-3) expression
      has been demonstrated in benign hepatobiliary diseases, but there are limited
      data regarding its expression in HCC. METHODS: Thirty consecutive cases of HCC
      from 1998 to 2003 were studied. Immunohistochemistry was performed on formalin
      fixed paraffin-embedded blocks of HCC using polyclonal antibody to TFF-3. TFF-3
      expression was classified as strong, moderate, weak, focal, and negative.
      Clinical data were obtained per an IRB-approved protocol. RESULTS: Median age was
      69 yr (range: 39-83 yr). Twenty- three patients were males and 7 were females.
      Treatments included hepatic resection (n = 16), chemo-embolization (n = 4),
      combined modality therapy (n = 5) and no treatment (n = 4). HCC was well
      differentiated in 12 (40%), moderately differentiated in 13 (43%), and poorly
      differentiated in 5 (17%) patients. TFF-3 expression was detected in 28/30
      (93.3%) patient samples. Sixteen patients (53%) had moderate and 1 (3%) patient
      had strong TFF-3 expression. Tumor/ normal tissue interface was assessable in 21
      cases; 11 cases expressed TFF-3 at the interface. There was a strong correlation
      between tumor grade and TFF-3 expression, wherein poorly differentiated tumors
      had moderate/strong TFF-3 expression (p = 0.008). There was no correlation
      between TFF-3 expression and survival (p = 0.77). Furthermore, there was no
      correlation among age, disease stage, and survival. CONCLUSION: TFF-3 is commonly
      expressed in HCC and its expression correlates with tumor grade.

PMID- 16110119
TI  - Doxorubicin and streptozotocin after failed biotherapy of neuroendocrine tumors.
AB  - BACKGROUND: Well-differentiated neuroendocrine tumors are treated primarily with
      somatostatin analogs and interferon-alpha. It is not clear what therapy should be
      applied after failed biotherapy. Our aim was to establish whether patients whose
      tumors rapidly progress under biotherapy may benefit from chemotherapy. PATIENTS
      AND METHODS: In 10 patients with metastatic neuroendocrine tumors (4 foregut, 3
      midgut, 1 retroperitoneal, and 2 of unknown origin) streptozotocin and
      doxorubicin were used as second-line or third-line therapy. Tumor response was
      assessed by computed tomography of the abdomen and thorax and measurement of
      tumor secretion products (serum chromogranin A, urinary 5-hydroxyindoleacetic
      acid). RESULTS: Three patients showed a radiological response over a mean time of
      30 mo (range: 7-67 mo). Median survival after initiation of chemotherapy was 50
      mo in patients with a response and 8 mo in non-responders. Three patients
      developed major side effects (nephrotoxicity, diabetes, and encephalopathy).
      CONCLUSION: Streptozotocin and doxorubicin produce poor response rates in
      patients with progressive neuroendocrine tumors after failed biotherapy, but may
      prolong life in those patients who show a tumor response.

PMID- 16110120
TI  - Potential role of flavonoids in the prevention of intestinal neoplasia: a review
      of their mode of action and their clinical perspectives.
AB  - Intestinal neoplasia (adenomas and carcinomas) can possibly be prevented by a
      diet rich in vegetables and fruits, treatment with aspirin and other nonsteroidal
      antiinflammatory drugs, and early colonoscopic removal of adenomas. Ballast,
      fiber, and secondary plant products could play a major role in colon cancer
      prevention. Recently there has been much experimental work in vitro and in vivo
      about flavonoids as inducers of bioprevention. Flavonoids are secondary plant
      products with a wide variety of beneficial biological properties, and they
      possess anticarcinogenic, antimutagenic, and antioxidative modes of actions.
      Flavonoids are the main components of a healthy diet containing fruits and
      vegetables and are concentrated especially in tea, apples, and onions. We will
      focus this review on flavonoids which are derived from tea products such as
      proanthocyanidins (green tea) and flavons (camomille tea). Oral supplementation
      with bioflavonoids derived from tea could be used in humans to prevent growth of
      intestinal neoplasia such as adenomatous polyps of the colon. Flavonoids are a
      large group of natural compounds of which only a few have been used in animal
      models, cell cultures, and enzyme studies to inhibit mutagenic and carcinogenic
      events. Their clinical mode of action was evaluated by epidemiological studies,
      but no intervention studies in humans have been performed so far. In vitro
      flavonoids can bind electrophils, inactivate oxygen radicals, prevent lipid
      peroxidation, and inhibit DNA oxidation. In cell cultures they increase the rate
      of apoptosis, inhibit cell proliferation, and angiogenesis. In vivo they can
      induce the activities of protective enzymes (conjugating enzymes such as
      glutathione transferases and glucuronosyl transferases) of the intestine and the
      liver. In models of intestinal polyposis, flavonoids suppress polyp formation.
      Some epidemiological studies show a protective effect of flavonoids contained in
      fruits, vegetables, and tea. Flavonoid mixtures of tea origin supplied as
      nutritional supplements could be studied as a new way of bioprevention of
      intestinal neoplasia (colon adenomas and cancer). Therefore, a controlled,
      randomized clinical study should be performed to evaluate the efficacy of
      flavonoids.

PMID- 16110121
TI  - Correlation between expression of orotate phosphoribosyl transferase and 5
      fluorouracil sensitivity, as measured by apoptosis index in colorectal cancer
      tissue.
AB  - BACKGROUND: 5-Fluorouracil remains a key drug in the treatment of colorectal
      cancer, and the development of a simple and effective test for selecting patients
      likely to benefit from postoperative adjuvant chemotherapy is an important
      objective. AIM OF THE STUDY: This study aimed to clarify the feasibility of
      measuring apoptotic cell rate (AI%) in tumor after short-term oral 5-fluorouracil
      administration prior to surgery with the objective of establishing a simpler
      method to test for sensitivity. METHODS: Forty-five colorectal cancer patients
      were allocated to two groups, and 21 patients were given oral 5-FU for 3 d prior
      to surgery. The AI% in surgical specimen, detected by TUNEL staining, was
      compared in the 5-FU-loaded and control groups. The correlation of AI% with 5-FU
      metabolic enzyme mRNA levels in tumor was also evaluated. RESULTS: The AI% was
      significantly higher in the tumor tissue of patients receiving 5-FU than in the
      control group (p < 0.0005). Although insignificant, thymidylate synthase mRNA
      level and orotate phosphoribosyl transferase mRNA demonstrated a weak positive
      correlation with AI%. CONCLUSIONS: The AI% measurement in tumor tissue following
      a 5-FU oral load for 3 d prior to surgery was feasible. It remains to be
      elucidated if this measurement as a new 5-FU sensitivity test reflects the
      prognosis with 5-FU-based postoperative adjuvant chemotherapy.

PMID- 16110122
TI  - Surgery for colorectal cancer in a low-volume unit: assessment of key issues in
      the achievement of acceptable clinical results.
AB  - BACKGROUND: The maintenance of modern therapeutic principles requires a proper
      case load to achieve acceptable surgical results. This may obligate
      administrative reorganization to overcome these problems and to provide an
      adequate level of cancer surgery. AIM: To assess the surgical results of patients
      coming for surgery for colorectal cancer in a low-volume non-academic unit during
      the past 15 yr. METHODS: 458 consecutive patients referred for surgery between
      1988 and 2001 in Kanta-Hame Central Hospital in Finland were analyzed regarding
      their disease, mode of surgery, and the immediate and long-term result. The data
      were collected from patient journals and from the National Centre of Statistics
      and analyzed in two successive periods. RESULTS: The number of patients with a
      localized disease (Dukes A + Dukes B) decreased during the followup from 49% to
      45%. A curative procedure was achieved in 68% in the first half and in 73% in the
      second half of the observation period. The immediate mortality was 5% and 2% in
      the two periods, respectively. The corrected 5-year survival according to the
      Dukes Classification was 92% (A), 69% (B), 41% (C ), and 6% (D). In curative
      surgery for rectal cancer, the incidences of local recurrence decreased from 21%
      to 9% (NS) and the use of permanent colostomy from 59 to 42% (NS). CONCLUSIONS:
      Acceptable immediate and long-term results in curative surgery for colorectal
      cancer can be achieved in a low-volume surgical unit. Nevertheless, owing to the
      low volume, the improvement of the results obligates team-based institutional
      specialization and careful consideration about the extensiveness of the primary
      procedure in case of cancer obstruction.

PMID- 16110123
TI  - Gastrinoma of the stomach: a case report.
AB  - Gastrinomas of the stomach are extremely rare endocrine tumors producing
      Zollinger-Ellison syndrome. We report here the case of a patient with gastrinoma
      of the stomach who presented regional and hepatic metastases at the time of
      diagnosis. The endocrine tumor was discovered incidentally 8 yr after the onset
      of symptoms related to peptic ulcer, which responded to medical treatment with a
      proton pump inhibitor. Surgery did not cure the patient, as demonstrated by
      provocative tests showing serum gastrin responses indicative of residual disease.
      A long-term treatment with the somatostatin analog lanreotide induced a
      biochemical response and was associated with a substantially stable disease.

PMID- 16110124
TI  - Pancreatic endocrine neoplasm can mimic serous cystadenoma.
AB  - A 57-yr-old female patient was referred to our hospital with a cystic lesion of
      the head of the pancreas that had been noted on abdominal computed tomography
      (CT). Endoscopic ultrasonography (EUS) showed a 3.0 cm rounded mass in the head
      of the pancreas. EUS images showed that the tumor had a solid component
      consisting of multiple microcysts separated by septae and a cystic component
      consisting of a macrocystic lesion. Thus, the tumor was suspected of being a
      serous cystadenoma (SCA). However, the histopathological diagnosis based on
      endoscopic ultrasound- guided fine-needle-aspiration biopsy (EUS-FNAB) was that
      of a pancreatic endocrine neoplasm (PEN). Surgical resection was performed.
      Despite having very similar macroscopic findings to SCA, microscopic examination
      revealed that the patient's tumor was definitely a PEN. This case suggests that
      it is very difficult to distinguish PENs from SCAs based solely on imaging
      methods. EUS-FNAB is essential for determining the appropriate therapeutic
      strategy, as it provides the histopathological diagnosis.

PMID- 16110125
TI  - Sudden unexpected death.
AB  - Sudden unexpected death is a major public health problem. Many cases could be
      prevented if they were anticipated through means of a better awareness among the
      medical community, new therapies based on early genetic screening, or corrected
      by countershock.

PMID- 16110126
TI  - Probiotics: the benefits of bacterial cultures.
AB  - Probiotics are bacterial cultures widely used in the treatment of disease. They
      are available without a prescription. Bacterial interference between types of
      bacteria and immunomodulation are the most common explanations as to why people
      may benefit from these treatments. The data on the use of probiotics in pediatric
      and adult diarrhea, inflammatory bowel disease, ileal pouchitis, urogenital
      infections, allergy, skin infections, and cancers are reviewed. Although
      generally safe, cases of complications from probiotic therapy are discussed, as
      well as potential problems that may develop.

PMID- 16110127
TI  - Aspirin for the primary prevention of cardiovascular disease: a comprehensive
      review.
AB  - Aspirin use for the primary prevention of cardiovascular disease should be
      targeted to patients with a high cardiovascular risk. Physicians should assess
      the risks and benefits of aspirin therapy for primary prevention and incorporate
      patient preferences.

PMID- 16110128
TI  - Noninvasive management of lower urinary tract symptoms and sexual dysfunction
      associated with benign prostatic hyperplasia in the primary care setting.
AB  - Most men who live to middle age and beyond will ultimately develop lower urinary
      tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), and many
      will also experience sexual dysfunction. Clinical studies indicate that most
      patients will experience improvement in BPH-related LUTS with alpha-adrenergic
      blockade or 5alpha-reductase inhibition. Recent studies suggest that alpha
      blockers and 5alpha-reductase inhibitors may help to slow the progression of
      LUTS; 5alpha-reductase inhibitors reduce the need for surgery and complications,
      such as acute urinary retention. Third-generation alpha-blockers (alfuzosin,
      tamsulosin) are infrequently associated with cardiovascular side effects, in
      contrast to their predecessors (doxazosin, terazosin, prazosin). This may provide
      an advantage for consideration as firstline therapy. alpha-Blocker therapy may
      also improve sexual functioning, with the exception of ejaculation disorders,
      predominantly associated with subtypeselective alpha-blockers. By contrast,
      5alpha-reductase inhibition is not recommended for men without demonstrable
      prostatic enlargement, may be associated with a long delay between treatment
      initiation and LUTS improvement, and is clearly associated with sexual side
      effects, including decreased libido, ejaculatory dysfunction, and erectile
      dysfunction. When choosing appropriate pharmacotherapy, the clinician should
      consider not only the expeditious relief of the presenting symptoms but also the
      patient's quality of life, including sexual function and potential long-term
      outcomes, such as acute urinary retention and the need for surgical intervention.

PMID- 16110129
TI  - Fluid management in hospitalized patients.
AB  - Intravenous fluid administration is critical to the care of hospitalized
      patients. Despite the lack of a clear consensus on fluid administration, one may
      use the principles in this article to develop an organized framework for patient
      care.

PMID- 16110130
TI  - Newer antidepressants and other nonhormonal agents for the treatment of hot
      flashes.
AB  - The reluctance to use estrogen in breast cancer survivors with hot flashes has
      extended to its use in healthy women since the 2002 publication of the Women's
      Health Initiative study. This article reviews the clinical development of
      nonhormonal agents as alternatives to hormonal therapy for the management of hot
      flashes.

PMID- 16110131
TI  - Percutaneous vertebroplasty: a review for the primary care physician.
AB  - The purpose of this article is to help primary care physicians who are often
      challenged with the management of vertebral compression fracture (VCF) by
      presenting clinical background and identifying candidates for percutaneous
      vertebroplasty, a minimally invasive procedure for treatment of VCF.

PMID- 16110133
TI  - The safety of full-dose chemotherapy with secondary prophylactic granulocyte
      colony stimulating factor (G-CSF) following a prior cycle with febrile
      neutropenia.
AB  - Secondary prophylactic administration of recombinant human granulocyte colony
      stimulating factor (G-CSF) following an episode of febrile neutropenia is
      recommended if maintenance of dose-intensity is desired. This policy was adopted
      in our center in patients treated with an intent for cure or durable complete
      response. The purpose of this study was to evaluate the safety and feasibility of
      this policy. Patients in whom neutropenia was associated with a life-threatening
      infection and those who developed prolonged myelosuppression were excluded. Fifty
      one patients who developed febrile neutropenia that required intravenous
      antibiotics following moderately myelotoxic chemotherapy were included. These
      patients received the next cycle of the same chemotherapy regime without dose
      modification but with the support of filgrastim (300 or 480 mg/d sc for at least
      10 consecutive days). Diagnoses included lymphoma (n = 19), breast cancer (n =
      15), germ cell tumor (n = 7), small-cell lung cancer (n = 5), and other solid
      tumors (n = 5). The incidence of febrile neutropenia during the first cycle given
      with filgrastim support (N1) was 8/51 (16%). Intravenous antibiotics were
      required for 3-7 d (median, 4.5 d). During the following cycle (N2), febrile
      neutropenia developed in 4/41 (10%) patients. Intravenous antibiotics were given
      for 2, 4, 5, and 7 d. Other dose-limiting toxicities developed in 1/51 patients
      who received N1 and in 1/41 patients who received N2. There was no drug-related
      death associated with either cycle. In conclusion, a policy of full-dose
      chemotherapy with secondary G-CSF support in patients who develop febrile
      neutropenia following moderately myelotoxic chemotherapy is relatively safe and
      feasible.

PMID- 16110132
TI  - Prognostic usage of V(H) gene mutation status and its surrogate markers and the
      role of antigen selection in chronic lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease
      with many patients surviving for decades with minimal or no treatment, whereas
      others succumb rapidly to their disease despite therapy. In recent years, new
      molecular prognostic factors have emerged in CLL that have significantly improved
      the subgrouping of the disease. One of the most important molecular predictors,
      the immunoglobulin V(H) gene mutation status, divides CLL into two prognostic
      groups, depending on the presence or absence of somatic hypermutation, where
      unmutated V(H) genes are associated with considerably worse prognosis than
      mutated V(H) genes. An exception to this appears to be CLL patients utilizing the
      V(H)3-21 gene as they have poor outcome irrespective of mutation status.
      Surrogate markers for the VH gene mutation status have been suggested, such as
      CD38 and ZAP-70 expression. However, the CD38 level was later shown to display
      poor correlation to the mutation status, although it may still serve as an
      independent prognostic factor. More promising is the expression levels of ZAP-70,
      which appears to be both a strong surrogate marker for V(H) gene mutation status,
      although discrepancies have been reported, as well as an independent prognostic
      marker. Immunoglobulin gene analysis has also indicated the possibility of
      antigen selection in CLL considering the significant bias in V(H) gene usage.
      Intriguingly, the V(H)3-21+ group and several other CLL subsets using certain
      V(H) genes was recently reported to display strikingly restricted immunoglobulin
      gene features, in both their heavy and light chain gene rearrangements, thus
      further high-lighting the possible role of antigen involvement in CLL
      development.

PMID- 16110134
TI  - Tumor parameters, clinical and pathological responses, medical management, and
      survival through time on 710 operable breast cancers.
AB  - The aim of the current study is an analysis of tumor parameters, clinical and
      pathological responses, medical management, and survival on 710 operable breast
      cancer patients who received neoadjuvant chemotherapy from 1982 to 2004 and were
      grouped into four successive periods according to diagnosis date: (1) 1982-1989;
      (2) 1990-1994; (3) 1995-1999; and (4) 2000-2004. Patients were treated by
      different neoadjuvant chemotherapies combinations: AVCF/M, TNCF, NEM, NET,
      TAXOTERE, FEC 50, 75, 100, FAC 50, and TAXOTERE-TNCF, mainly in successive
      prospective phase II trials. They received a median number of six cycles (range,
      1-9). After primary chemotherapy, patients underwent a surgery and a
      radiotherapy. In case of significant residual disease, some patients received
      additional courses of chemotherapy. In addition, menopausal patients with
      hormonal receptor-positive tumors received tamoxifen for 5 yr. Clinical factors
      had some remarkable variations with time. The median age of the patients was 49.5
      yr (range, 26-81). The size of the tumor was significantly greater from 1995;
      conversely, clinical lymph-node involvement was lower in period 4 than in the
      first period. The percentage of invasive ductal carcinoma and of SBR III tumors
      increased about 20% from 1982-1989 to 2000-2004. The number of positive hormonal
      receptors increased from 38.3% in period 1 to 74% in period 4. The clinical
      response rate improved recently from before 1990. The pathological response rate
      was greater in periods 2 and 3 than in periods 1 and 4. An adjuvant
      hormonotherapy became progressively more frequently given (44.7 for period 1 and
      73.3% for period 4). Finally, no significant difference was found when we
      compared overall and disease-free survival through the four periods. It appears
      that the progressive increase of tumor burden was compensated by more effective
      treatments.

PMID- 16110135
TI  - The value of serum levels of IL-6, TNF-alpha, and erythropoietin in metastatic
      malignant melanoma: serum IL-6 level is a valuable prognostic factor at least as
      serum LDH in advanced melanoma.
AB  - In order to study the relation to the metastatic profile and survival, we
      evaluated the association between pretreatment serum levels of IL-6, TNF-alpha,
      and erythropoietin (EPO) and metastatic distribution and survival in 16 patients
      with metastatic malignant melanoma. IL-6 and TNF-alpha immunoassay (R&D Systems,
      Inc. Minneapolis, USA) employs the quantitative sandwich enzyme immunoassay
      technique. The Quantikine IVD EPO ELISA (R&D Systems, Inc.) is based on the
      double-antibody sandwich method. The baseline serum IL-6 and EPO levels were
      significantly higher in patients with metastatic malignant melanoma than in the
      control group (p = 0.009 and p = 0.033, respectively). Serum IL-6 levels were
      higher in patients with weight loss (p = 0.02), who were anemic (p = 0.026), with
      elevated serum LDH levels (p = 0.028), and who were chemotherapy nonresponding (p
      = 0.016). The relationship of serum IL-6 concentration to the tumor burden was
      not determined. Only serum EPO level was influenced by hemoglobin status (p =
      0.001). No difference was shown among these three parameters. Elevated serum IL-6
      concentration (p = 0.002) was found to be an adverse prognostic factor in
      patients with poor performance status, weight loss, low serum hemoglobin,
      elevated serum LDH, and unresponsive to chemotherapy. On the other hand, both
      serum TNF-alpha and EPO levels were of no prognostic value. Serum levels of IL-6
      were found to be prognostic factors as valuable as serum LDH levels in patients
      with metastatic malignant melanoma. Their prognostic value should be further
      evaluated in a larger patient population.

PMID- 16110136
TI  - Therapeutic efficacy by recombinant human granulocyte/monocyte-colony stimulating
      factor on mucositis occurring in patients with oral and oropharynx tumors treated
      with curative radiotherapy: a multicenter open randomized phase III study.
AB  - BACKGROUND: Previous studies suggested granulocyte-macrophage-colony stimulating
      factor (GM-CSF) might be beneficial for radiotherapy-induced mucositis. This
      trial examined the efficacy of GM-CSF in reducing mucositis of the oral cavity
      and/or oropharynx compared with conventional treatment. METHODS: Mucositis,
      documented by a five-grade scale, was defined in patients with tumors of the head
      neck. Centers were allowed to use their own preferred fractionation regimen.
      Randomization to treatment was decided before radiotherapy. Treatment with GM-CSF
      4 microg/kg/d subcutaneous, started when patients displayed a mucositis score >
      or = 1.5. RESULTS: Ninety-two patients entered the study according to intention
      to-treat principle. Twenty did not reach a mucositis index of 1.5. Sixty-one
      patients were included in the statistical analysis. Forty-five percent of the
      patients randomized to receive GM-CSF had a significant reduction of the
      mucositis more than one grade compared to 9% of the conventional treated.
      CONCLUSIONS: In severe mucositis, GM-CSF is more effective than conventional
      treatment.

PMID- 16110137
TI  - Phase I trial of infusional cyclophosphamide, doxorubicin, and etoposide plus
      granulocyte-macrophage colony stimulating factor (GM-CSF) in non-Hodgkin's
      lymphoma.
AB  - PURPOSE: To determine the recommended phase II dose (RPTD) of a 96-h continuous
      intravenous infusion (CIVI) of cyclophosphamide (200, 300, or 400 mg/m2/d) and
      etoposide (60 or 90 mg/m2/d) when used in conjunction with doxorubicin (12.5
      mg/m2/d) (CDE) given every 28 d plus granulocyte-macrophage colony stimulating
      factor (GM-CSF) in patients with poor prognosis non-Hodgkin's lymphoma (Group A),
      and the same regimen given every 21 d (Group B). METHODS: In Group A, infusional
      CDE was repeated every 28 d, GM-CSF (250 microg/m2) was given subcutaneously from
      d 6 until neutrophil recovery, with dose escalation in cohorts of three to six
      evaluable patients. The RPTD of cyclophosphamide and etoposide established in
      Group A was then used with CDE given every 3 wk (Group B) with GM-CSF given on d
      6-20, and dose escalation was attempted again. RESULTS: In Group A, the RPTD of
      cyclophosphamide and etoposide were 300 mg/m2/d and 90 mg/m2/d, respectively;
      prolonged neutropenia was the dose-limiting toxicity. In Group B, use of GM-CSF
      on d 6-20 did not facilitate dose escalation above the RPTD established in Group
      A. Complete response occurred in 13/26 patients (50%) with no prior chemotherapy,
      and in 4/16 patients (25%) who had relapsed after prior chemotherapy.
      CONCLUSIONS: Because of the increase in dose and dose-density afforded by the
      administration of GM-CSF, the relative dose intensity was increased by twofold
      for cyclophosphamide (400 vs 200 mg/m2/wk) and etoposide (120 vs 60 mg/m2/wk),
      and by 1.3-fold for doxorubicin (16.7 vs 12.5 mg/m2/wk).

PMID- 16110138
TI  - Paclitaxel, cisplatin, leucovorin, and continuous infusion fluorouracil followed
      by concomitant chemoradiotherapy for locally advanced squamous cell carcinoma of
      the head and neck: a Hellenic Cooperative Oncology Group Phase II Study.
AB  - The primary objective of this phase II study was to access the complete response
      (CR) rate to a new innovative induction regimen in patients with locally advanced
      head and neck cancer (LA-HNC). From October 2000 until October 2003 a total of 38
      eligible patients (33 men and 5 women) entered the study. The large majority of
      them presented with a performance status of 0-1 and with clinical stage IV
      disease. Treatment consisted of three cycles of induction chemotherapy (IC) with
      paclitaxel 175 mg/m2 in a 3-h infusion on d 1, leucovorin (LV) 200 mg/m2 over 20
      min immediately followed by FU 400 mg/m2 bolus and then 600 mg/m2 as a 24-h
      continuous infusion on d 1 and 2 and a cisplatin 75 mg/m2 over 1-h infusion on d
      2 every 3 wk. This was then followed by radiation (70 Gy) and weekly cisplatin 40
      mg/m2. After the completion of IC, 6/38 (16%) patients had CR. The CR rate was
      increased to 66% post-concomitant chemoradiotherapy (CCRT). Neutropenia (37.5%),
      pain (62%), nausea/vomiting (21%), and alopecia (79%) were the most frequent side
      effects during IC. The most pronounced toxicities during chemoradiotherapy were
      stomatitis (62.5%) and xerostomia (53%). Median time to progression was 11.0 mo
      and median survival 16.7 mo. One- and 2-yr survival rates were 73% and 38%,
      respectively. In conclusion, this novel induction regimen is active, is well
      tolerated, and can be successfully followed by CCRT with weekly cisplatin. CCRT
      should remain standard treatment for patients with LA-HNC. Novel induction
      combinations, such as that reported in the present study, should be evaluated in
      combination with CCRT only in the context of clinical trials.

PMID- 16110139
TI  - A phase II study of dose-intensified weekly concomitant administration of
      cisplatin and irinotecan in chemonaive patients with extensive-disease small-cell
      lung cancer.
AB  - Irinotecan/cisplatin (IP) is an active regimen for extensive-disease small-cell
      lung cancer (ED-SCLC). However, the optimal dose/schedule is unsettled. To
      evaluate the efficacy and safety of a dose-intensified, weekly concomitant
      administration of IP, we conducted a phase II study in chemo-naive patients with
      ED-SCLC. Between October 2001 and February 2004, 37 patients were enrolled.
      Twenty-nine (78%) were male, 21 (57%) had ECOG PS 0 or 1, and the median age was
      62 yr. The initial six patients received cisplatin 50 mg/m2 followed by
      irinotecan 90 mg/m2 iv on d 1 and 8 of a 21-d cycle (dose level I), with one
      treatment-related death, three febrile neutropenias. Thereafter, the doses of
      cisplatin and irinotecan were reduced to 40 mg/m2 and 80 mg/m2, respectively
      (dose level II). The treatment was continued for up to six cycles. The overall
      response rate was 97%, with a complete response (CR) rate of 26%. The median
      duration of response was 6.4 mo (range, 1.6-13.1 mo). At a median follow-up of
      27.3 mo, the median survival time was 11.1 mo and 1- and 2-yr survival rates were
      44.1% and 11.8%, respectively. The median progression-free survival (PFS) was 6.0
      mo (range, 1.5-13.1 mo) and 1-year PFS rate was 7%. Major grade 3 or 4 toxicities
      included neutropenia (89%), anemia (59%), and diarrhea (27%). Despite of
      significant myelosuppresion, this dose-intensified weekly concomitant
      administration of cisplatin and irinotecan was feasible. This dose-schedule
      showed promising activity with high rate of complete remission in patients with
      ED-SCLC.

PMID- 16110140
TI  - Signaling molecules and cytokine production in T cells of patients with B-cell
      chronic lymphocytic leukemia (B-CLL): comparison of indolent and progressive
      disease.
AB  - T-cell dysfunction in B-CLL patients might be attributed to altered expression of
      components of the TCR/CD3 complex and associated intracellular tyrosine kinases.
      Four-color flow cytometry was applied to the expression of these molecules as
      well as the T-cell regulatory cytokines (IFN-gamma and IL-4) in B-CLL patients
      with indolent and progressive disease. Intracellular levels [mean fluorescent
      intensity (MFI)] of IFN-gamma and IL-4 in both CD4 and CD8 T cells of both
      patient groups were significantly higher than in healthy donors. Absolute number
      of IL-4 producing CD4 T cells in patients with indolent was significantly higher
      than in healthy donors. The expression level (MFI) of the CD3-zeta chain was
      higher in patients than in normal donors as well as ZAP-70 in patients with
      indolent disease as compared to healthy donors and progressive patients. No
      significant difference was noted in the expression of p56lck, p59fyn, and PI3
      kinase between healthy donors and patients or between the patient subgroups. The
      results indicate multiple T-cell abnormalities especially in indolent-stage B-CLL
      suggesting a state of chronic and aberrant activation. This information might be
      of significance when studying the immunobiology of B-CLL as well as developing
      new therapeutic approaches.

PMID- 16110141
TI  - Liver resection after irinotecan, 5-fluorouracil, and folinic acid for patients
      with unresectable colorectal liver metastases: a multicenter phase II study by
      the Cancer Therapeutic Research Group.
AB  - The main objectives of this study were to assess the use of irinotecan, 5
      fluorouracil (5-FU), and leucovorin (FA) as neoadjuvant chemotherapy for patients
      with unresectable colorectal liver metastases and to determine the response rate
      and proportion of patients that could be down-staged to resectable tumors. Forty
      patients were treated with irinotecan (180 mg/m2 over 30 min) on d 1, FA (200
      mg/m2 over 30 min) followed by 5-FU (400 mg/m2 bolus and continuous infusion of
      600 mg/m2 over 22 h) on d 1 and 2 every 2 wk. The overall response rate was 55%
      (95% CI: 39.5-70.4%). The progression-free survival was 12.1 mo (95% CI: 11.4
      14.8 mo). The median overall survival was 20 mo (95% CI: 17.7-26.6 mo). Four
      patients (10%) have undergone liver resection after a median of eight cycles.
      Those patients remained alive with a median follow up period of 33 mo. The
      principal grade 3-4 toxicity was neutropenia in 20 patients (50%). We conclude
      that the regimen of irinotecan/5-FU/FA was highly active in patients with
      colorectal cancer and liver metastases with limited toxicity. In a subgroup of
      patients with initial inoperable liver metastases, this regimen was able to down
      stage the disease to an operable stage.

PMID- 16110142
TI  - Isolated skeletal muscle recurrence of the paranasal sinus lymphoma in complete
      remission.
AB  - Paranasal sinuses represent an unusual site for non-Hodgkin's lymphoma (NHL).
      Failure after treatment for paranasal sinus lymphomas is usually in non
      irradiated sites and marginal sites. With this case report, we present a
      paranasal sinus lymphoma in complete remission with an isolated recurrence in
      skeletal muscle of the right lower limb for the first time in the literature.

PMID- 16110143
TI  - Mantle cell lymphoma presenting with paraproteinemia.
AB  - Mantle cell lymphoma (MCL) is most frequently diagnosed by the routine
      histological (HP) and immunohistochemical (IH) examination. Herein we present a
      case of 47-yr-old female with general lymphadenopathy and leukemic blood picture.
      She was initially diagnosed with marginal zone lymphoma (MZL). This diagnosis was
      based not only on the HP/IH examination but also on the presence of IgM
      paraproteinemia. Flow cytometry (FCM) examination was helpful in making of the
      final diagnosis of MCL. Fluorescence in situ hybridization and cyclin D1 mRNA
      detection by RT-PCR additionally confirmed the MCL diagnosis. The IgM
      paraproteinemia is rare in MCL, although is a common feature of
      lymphoplasmacytoid lymphomas (LPL) and is considered a major characteristic of
      Waldenstrom's macroglobulinemia (WM).

PMID- 16110145
TI  - Paul Ehrlich's "Mastzellen"--from aniline dyes to DNA chip arrays: a historical
      review of developments in mast cell research.
AB  - It has been more than a century since the discovery of the mast cell by the
      genius and tenacity of Paul Ehrlich, who described this cell when he was a
      medical student. One cannot deny that this discovery also coincides with the
      golden age of immunology. The discovery of this important cell type in
      immunological history was no serendipity: it was a result of Ehrlich's prodigious
      laboratory talent and his ability to combine intuition and deduction despite the
      limited resources of his times. Since then, we have learned much more about the
      immune response, immunoglobulin E, and the development and function of mast cells
      in various pathological states. What follows is a review of Paul Ehrlich's
      discovery of the mast cell (mastzellen) and a chronological review of subsequent
      developments in mast cell research, including the recent use of proteomics and
      genomics to understand mast cell biology.

PMID- 16110146
TI  - The human mast cell: an overview.
AB  - Mast cells are fascinating, multifunctional, tissue-dwelling cells that have been
      traditionally associated with the allergic response. However, recent studies
      suggest these cells may be capable of regulating inflammation, host defense, and
      innate immunity. The purpose of this review is to present salient aspects of mast
      cell biology in the context of mast cell function in physiology and disease.
      After their development from bone marrow-derived progenitor cells that are primed
      with stem cell factor, mast cells continue their maturation and differentiation
      in peripheral tissue, developing into two well-described subsets of cells, MC(T)
      and MC(TC) cells. These cells can be distinguished on the basis of their tissue
      location, dependence on T lymphocytes, and their granule contents. Mast cells can
      undergo activation by antigens/allergens, superoxides, complement proteins,
      neuropeptides, and lipoproteins. After activation, mast cells express histamine,
      leukotrienes, and prostanoids, as well as proteases, and many cytokines and
      chemokines. These mediators may be pivotal to the genesis of an inflammatory
      response. By virtue of their location and mediator expression, mast cells may
      play an active role in many diseases, such as allergy, parasitic diseases,
      atherosclerosis, malignancy, asthma, pulmonary fibrosis, and arthritis. Recent
      data also suggest that mast cells play a vital role in host defense against
      pathogens by elaboration of tumor necrosis factor alpha. Mast cells also express
      the Toll-like receptor, which may further accentuate their role in the immune
      inflammatory response. This chapter summarizes the many well-known and novel
      functional aspects of human mast cell biology and emphasizes their unique role in
      the inflammatory response.

PMID- 16110147
TI  - Mast cells in allergy and autoimmunity: implications for adaptive immunity.
AB  - As in the fashion industry, trends in a particular area of scientific
      investigation often are fleeting but then return with renewed and enthusiastic
      interest. Studies of mast cell biology are good examples of this. Although dogma
      once relegated mast cells almost exclusively to roles in pathological
      inflammation associated with allergic disease, these cells are emerging as
      important players in a number of other physiological processes. Consequently,
      they are quickly becoming the newest "trendy" cell, both within and outside the
      field of immunology. As sources of a large array of pro- and anti-inflammatory
      mediators, mast cells also express cell surface molecules with defined functions
      in lymphocyte activation and trafficking. Here, we provide an overview of the
      traditional and newly appreciated contributions of mast cells to both innate and
      adaptive immune responses.

PMID- 16110148
TI  - Analysis of MC(T) and MC(TC) mast cells in tissue.
AB  - The MC(TC) and MCT types of human mast cells initially were recognized on the
      basis of the protease compositions of their secretory granules, with tryptase,
      chymase, carboxypeptidase A3, and cathepsin G in the former and only tryptase in
      the latter. Antibodies against chymase and tryptase traditionally have been used
      to distinguish these mast cell types from one another. Antitryptase antibodies
      label all mast cells; antichymase labels only the MC(TC) type. To identify both
      types in a tissue section, a sequential double-labeling scheme was developed to
      first stain chymase-positive cells, thereby blocking their recognition by the
      antitryptase antibody, which will label only the chymase-negative mast cells. In
      general, these immunocytochemical techniques are more sensitive and specific than
      classical histochemical techniques for detecting mast cells.

PMID- 16110149
TI  - Mast cell ultrastructure and staining in tissue.
AB  - Mast cells are bone marrow-derived cells that are widely distributed in the
      tissue. They are found predominantly in the subepithelial tissue near blood
      vessels and nerves and usually are sprinkled diffusely without forming clusters.
      In tissue sections stained with hematoxylin and eosin, normal mast cells usually
      display a round-to-oval nucleus with clumped chromatin and indistinct or no
      nucleoli. They have moderately abundant cytoplasm and are oval, spindle, or
      polygonal in shape. The cytoplasm is amphophilic, and sometimes small slightly
      eosinophilic granules may be visible. Hematoxylin and eosin staining is not a
      specific or reliable method for detecting mast cells in tissue sections because
      of variable cellular morphology. For confirmation of mast cells, special stains,
      such as mast cell tryptase or CD117, are required.

PMID- 16110150
TI  - Expression of cell surface antigens on mast cells: mast cell phenotyping.
AB  - During the past few decades, a number of functionally important cell surface
      antigens have been detected on human mast cells (MCs). These antigens include the
      stem cell factor receptor (SCFR/CD117), the high-affinity immunoglobulin E
      receptor, adhesion molecules, and activation-linked membrane determinants.
      Several of these antigens (CD2, CD25, CD35, CD88, CD203c) appear to be
      upregulated on MCs in patients with systemic mastocytosis and therefore are used
      as diagnostic markers. Quantitative measurement of these markers on MCs is thus
      of diagnostic value and is usually performed by multicolor-based flow cytometry
      techniques utilizing a PE- or APC-labeled antibody against CD117 for MCs
      detection. This chapter gives an overview about the methods of staining of MC in
      various tissues with special reference to novel diagnostic markers applied in
      patients with suspected systemic mastocytosis.

PMID- 16110151
TI  - Identification of mast cells in the cellular response to myocardial infarction.
AB  - Myocardial infarction is associated with an acute inflammatory response, leading
      to replacement of injured cardiomyocytes with granulation tissue. Mast cells are
      actively involved in postinfarction inflammation by releasing histamine and tumor
      necrosis factor-alpha, triggering a cytokine cascade. During the proliferative
      phase of healing, mast cells accumulate in the infarct and may regulate fibrous
      tissue deposition and angiogenesis by releasing growth factors, angiogenic
      mediators, and proteases. This chapter describes simple and reliable methods used
      to identify mast cells in control and infarcted canine hearts. Toluidine blue
      staining, labeling with conjugated avidin, and tryptase histochemistry are useful
      in the detection of mast cells in canine tissues. In the healing infarct, mast
      cells are associated with other cell types that are important for granulation
      tissue formation. We present immunohistochemical methods identifying monocytes,
      neutrophils, macrophages, endothelial cells, myofibroblasts, and smooth muscle
      cells in dog infarcts. These techniques are useful tools for pathological studies
      in canine models.

PMID- 16110152
TI  - Growth of human mast cells from bone marrow and peripheral blood-derived CD34+
      pluripotent progenitor cells.
AB  - Human mast cells (HMCs) are derived from a CD34+ pluripotent progenitor cell that
      is Kit (CD117+), CD13+, Fc epsilonRI- and lacks lineage-specific surface markers.
      Bone marrow and peripheral blood are two tissue sources available for obtaining
      CD34+ progenitor cells from which to culture HMCs. CD34+ cells can be isolated
      and enriched by magnetic separation columns and stored under specific conditions
      until ready for use. Alternatively, enriched CD34+ cells may be immediately
      cultured in serum-free culture media containing recombinant human stem cell
      factor (rhSCF), rhIL-6, and rhIL-3 (first week only). Weekly hemidepletions and
      the removal of adherent cells and/or debris enables the investigator to obtain
      HMC cultures, identified by Wright-Giemsa and acidic toluidine blue stains, by 8
      10 wk.

PMID- 16110153
TI  - Culture of human mast cells from hemopoietic progenitors.
AB  - The survival of hemopoietic stem cells in culture is suppressed by various
      cytokines and stimuli. The development of human mast cells also is affected by
      these stem cell-inhibitory mechanisms because it requires a much-longer period as
      compared with the development of other cell lineages. This chapter introduces the
      method of forming human mast cell colonies by culturing purified cord blood cells
      and peripheral blood cells in serum-free methylcellulose supplemented with stem
      cell factor and interleukin-6 for 6 wk. Mast cells in colonies can be retrieved
      by dissolving methylcellulose, and can be maintained in liquid medium for more
      than six months. This method should be useful for obtaining non-neoplasmic
      functional human mast cells with high methodological reproducibility.

PMID- 16110154
TI  - Isolation, culture, and characterization of intestinal mast cells.
AB  - Mast cells are bone-marrow-derived tissue cells typically located at barrier
      sites of the body, such as skin, mucosal barriers, or blood barriers, that is,
      around blood vessels. This location suggests that mast cells might have a
      function as immunological "gate-keepers" or "watch dogs" and, indeed, some recent
      functional data support this idea. Mast cells derive from myeloid progenitors,
      but in contrast to other myeloid cells, they leave the bone marrow in an immature
      state; therefore, mast cells are not found in the blood under normal conditions.
      For full maturation, the tissue environment is necessary. Thus, mature mast cells
      can be only isolated from tissue such as skin or mucosal sites, which makes mast
      cell isolation rather complicated. Alternatively, mast cell progenitors can be
      isolated from the bone marrow, peripheral blood, or cord blood, which is easier
      but requires subsequent in vitro maturation of mast cells as far as possible
      using cytokines. This chapter describes a rather new technique of mast cell
      isolation from human intestinal mucosal tissue yielding approx 1-5 million pure
      and viable human mast cells suitable to perform functional and cell culture
      experiments.

PMID- 16110155
TI  - Activation of nuclear factor-kappaB.
AB  - Nuclear factor-kappaB (NF-kappaB) is a key transcription factor that regulates
      the expression of genes involved in immune and inflammatory responses and in cell
      death and survival. This chapter describes in detail the method for measuring the
      NF-kappaB binding activity in the cultured human mast cell line HMC-1 using the
      electrophoretic mobility shift assay: the activation of NF-kappaB was illustrated
      by adding lipopolysaccharide to mast cells, nuclear proteins were isolated, and
      the NF-kappaB binding activity was determined. We also demonstrate the
      specificity of the NF-kappaB binding activity using a competition and supershift
      assay with specific antibodies that recognize NF-kappaB subunits p50 and p65.
      Lipopolysaccharide caused a rapid and significant increase in NF-kappaB binding
      activity.

PMID- 16110156
TI  - Analysis of mitogen-activated protein kinase activation.
AB  - The biological functions of mast cells are regulated by several protein kinases,
      including the tyrosine kinases Fyn, Lyn, Syk, and FAK and the serine/threonine
      kinases Akt and PKC alpha/beta. The mitogen-activated protein kinases
      extracellular signal-regulated kinases, JNK, and p38MAPK also play a significant
      role in the regulation of mast cell biological function. This chapter will detail
      recent advances in determining mitogen-activated protein kinase activation in
      single cells. These methods are applicable to studies of signal transduction in
      mast cells.

PMID- 16110157
TI  - Microarray and gene-clustering analysis.
AB  - Human mast cells are capable of secreting a plethora of inflammatory mediators
      and cytokines that may play a pivotal role in innate immune and inflammatory
      responses. Activation of mast cells by antigen and immunoglobulin E (IgE) results
      in signaling, gene expression, and expression of inflammatory mediators. Although
      a variety of techniques have been used to evaluate mast cell biology, recent
      advances in molecular techniques have provided unprecedented tools to study these
      cells. The complimentary deoxyribonucleic acid (DNA) oligonucleotide microarray,
      or DNA-chip technology, allows simultaneous monitoring of gene expression,
      provides a format for identifying genes as well as changes in their activity on a
      whole genome scale, and potentially offers a global view of pathophysiologic
      changes. This chapter reviews the use of DNA-chip technology in studying the
      expression of genes (transcriptional profiling) in activated human mast cells
      obtained from cultured cord blood-derived mononuclear cells and comments on the
      use of bioinformatics on analysis of gene expression. The most powerful
      applications of transcriptional profiling involve identification of the common
      patterns of gene expression across many experiments using various gene-clustering
      analyses. Several techniques have been used for the analysis of gene-expression
      data including hierarchical clustering and self-organizing maps. In this chapter,
      a general laboratory protocol for array analysis currently being used in our
      laboratory and the use of bioinformatics is discussed. Although the focus is on
      Affymetrix oligonucleotide arrays, the techniques described are generally
      applicable to expression data generated using other array formats.

PMID- 16110158
TI  - Techniques to study Fc epsilonRI signaling.
AB  - Mast cells are the crucial effector cells for allergic reactions. They are
      activated through the aggregation of the high-affinity immunoglobulin E (IgE)
      receptor (Fc epsilonRI) with allergen and allergen-specific IgE. Tyrosine
      phosphorylation of Fc epsilonRI subunits and various signaling proteins is an
      initial triggering event, leading to the activation of several signaling pathways
      in mast cells. Much has been learned from analysis of mast cells derived from
      gene-targeted mice. Therefore, in this chapter we will first describe how to
      generate mast cells from mouse bone marrow cells and how to correct the genetic
      defect by retroviral transduction. Then, we will describe how to assess early
      activation events by measuring several protein-tyrosine kinases and
      serine/threonine kinases such as protein kinase B (= Akt), protein kinase C, and
      JNK. As signal transduction is highly dependent on protein-protein interactions,
      we will describe experimental details of co-immunoprecipitation methods that are
      used to confirm such interactions.

PMID- 16110159
TI  - Human mast cell proteases: activity assays using thiobenzyl ester substrates.
AB  - Human mast cells contain proteases that are important functional components and
      serve as markers of mast cell activation or degranulation. Although tryptase is
      the best recognized mast cell protease, chymase and Cathepsin G also are found in
      some human mast cells. Methods for measuring the activities of these enzymes
      using sensitive synthetic peptide thiobenzyl ester substrates are described in
      this chapter. Using a visible plate reader with kinetic software femtomole
      quantities of these proteases can be measured. These methods are demonstrated in
      assays of tryptase and chymase in cell-free extracts of the HMC-1 and 5C6 human
      mast cell lines, as well as in extracts of cord blood derived mast cells.

PMID- 16110160
TI  - Mast cell histamine and cytokine assays.
AB  - Mast cells are crucial to the development of chronic allergic inflammation and
      are likely to play a critical role in host defense. In this chapter methodology
      for histamine and cytokine assays is provided. Crosslinkage of IgE receptor I (Fc
      epsilonRI) on cord blood-derived mast cells by myeloma IgE and anti-human IgE is
      used to induce histamine release. Histamine levels were measured in the culture
      supernatants using an enzyme-linked immunosorbent assay. A human mast cell line
      (HMC-1), derived from a patient with mast cell leukemia, was activated with
      interleukin (IL)-1beta to study cytokine production and gene expression. Cytokine
      gene expression was evaluated by reverse transcriptase polymerase chain reaction
      and cytokine production was assayed in culture supernatants using an enzyme
      linked immunosorbent assay kit.

PMID- 16110161
TI  - Measurement of mast cell cytokine release by multiplex assay.
AB  - Mast cells are highly responsive cells that are capable of secreting a variety of
      inflammatory mediators, including histamine, heparin, serine proteases,
      leukotrienes, prostaglandins, and thromboxanes. Studies from several laboratories
      have demonstrated that mast cells have the capacity to produce a variety of
      cytokines in response to various stimuli. Characterization of the cytokine
      profiles in mast cells has routinely been determined by the performance of
      individual enzyme-linked immunosorbent assays. This process is expensive, time
      consuming, and requires a great deal of material to characterize multiple
      cytokines. In this chapter, we describe a multiplex cytokine assay to detect 17
      cytokines simultaneously in 50 microL of culture supernatant derived from
      stimulated human cord blood-derived mast cells.

PMID- 16110162
TI  - Assays for histamine-releasing factors: from identification and cloning to
      discovery of binding partners.
AB  - When using a model to study disease, it may be advantageous to identify molecules
      responsible for biologic functions observed in the model to better understand the
      disease process being studied. The late phase reaction is used as a model for
      chronic inflammation, and the histamine releasing activity observed from late
      phase fluids was thought to be an important factor in the propagation of symptoms
      that remain in both the late-phase reaction and in chronic inflammation, when the
      offending antigen is no longer present. Purification from biologic fluids and
      identification may be helpful in understanding the role of the histamine
      releasing factors in inflammation. Once the specific molecule is identified and
      cloned, techniques such as yeast two-hybrid screens and co-immunoprecipitation
      experiments can be used to identify binding partners and further elucidate the
      role of the cloned molecule. The purification and cloning of human recombinant
      histamine-releasing factor and the subsequent yeast two-hybrid screen and co
      immunoprecipitation will be described to illustrate how any functionally defined
      molecule can be investigated.

PMID- 16110163
TI  - Assays for nitric oxide expression.
AB  - The purpose of this chapter is to review the analytical methodology specifically
      associated with studying the role of nitric oxide (NO) in mast cell physiology
      and biochemistry. The methodology for measuring cellular secretion of nitric
      oxide with Griess Reagent will be described in detail, as well as the use of 4,5
      diaminofluorescein diacetate for continuous monitoring of nitric oxide production
      in live cells. We will point out the limitations of the analytical techniques and
      also indicate areas in which promising analytical techniques have not yet been
      applied to the study of mast cell physiology, that is, new research
      opportunities. In addition to reviewing the methodology associated with measuring
      NO itself, we will briefly touch upon some analytical methods important in
      characterizing the biochemical products formed from nitric oxide (e.g., 3
      nitrotyrosine).

PMID- 16110164
TI  - Endothelial cell activation by mast cell mediators.
AB  - Mast cells are important cells of the immune system, and their secretory products
      regulate many vascular functions. Although considerable interest is focused on
      the role of mast cells and infectious agents in atherosclerosis, whether or not
      mast cell mediators act in concert with bacterial agents to regulate endothelial
      activation is not known. Here, we have described experimental techniques and
      presented related results to demonstrate how mast cell granule (MCG) mediators
      and bacterial products synergize endothelial cell inflammatory responses. The
      described methods outline: (1) the collection of rat peritoneal mast cells; (2)
      preparation of MCGs; (3) co-culture of human endothelial cells with mast cell
      granules; (4) determination of the regulation of endo- thelial cell inflammatory
      responses; (5) demonstration of the role of MCG protease and histamine in the
      regulation of endothelial cell function; (6) amplification of lipopolysaccharide
      induced signal transduction pathways by mast cell granules; (7) elucidation of
      histamine-induced amplification of endothelial cell responses to Gram-negative
      and Gram-positive bacterial cell wall components; and (8) determination of the
      expression of Toll-like receptor 2 and 4. We hope the techniques described here
      can be used for designing experiments focusing on the regulatory role of mast
      cell mediators on cell functions.

PMID- 16110165
TI  - Co-culture of mast cells with fibroblasts: a tool to study their crosstalk.
AB  - Mast cell development, function, and survival are likely to be regulated by a
      complex interplay of cellular signaling. Usually, these signals derive from the
      cellular milieu associated with the specific mast cell environment in health or
      disease conditions. A major methodological issue in studying in vitro mast cells,
      as well as any other tissue dwelling cell, is the essential lack of all the
      tissue-derived signals. Because some of the signals can be unknown, the in vivo
      system they form is virtually impossible to mimic completely in vitro. The mast
      cell-fibroblast co-culture system partially overcomes this problem and is the
      main topic of this chapter. The experimental importance of mast cell-fibroblast
      co-culture for the mast cells derives mainly from two reasons: first, fibroblasts
      constitute a major cellular scaffold of the tissues where mast cells dwell in the
      body, and as such are one of the fundamental cells participating in mast cell
      regulation in vivo and, second, there is an analogy with the traditional model of
      allergic inflammation, where the late, chronic phase is characterized by mast
      cell-structural cell crosstalk and eventual fibrotic outcome. Therefore, the co
      culture system can be viewed as a suitable tool to investigate mast cell
      fibroblast crosstalk.

PMID- 16110166
TI  - Detection of epsilon class switching and IgE synthesis in human B cells.
AB  - We observed that mast cells, as other cells expressing the CD40 ligand CD154, can
      trigger IgE synthesis in B cells in the presence of interleukin (IL)-4. Numerous
      complementary techniques can be used to follow the succession of molecular events
      leading to IgE synthesis. This chapter will illustrate how human B cells (naive
      or memory) can be purified, stored, and cultivated in medium that is permissive
      for IgE synthesis and stimulated with IL-4 or IL-13 and CD40 activation, the
      latter being induced by soluble CD154, anti-CD40 antibodies, or CD154-expressing
      cells. All these molecules are expressed by mast cells. The quantification of the
      epsilon-sterile transcript synthesis by polymerase chain reaction or Northern
      blot, the epsilon excision circles produced during immunoglobulin heavy chain
      locus rearrangement by polymerase chain reaction, and the IgE production by
      enzyme-linked immunosorbent assay will be described.

PMID- 16110167
TI  - Gene silencing using small interference RNA in mast cells.
AB  - Small interfering RNA (siRNA) is a potent and specific method of inducing gene
      silencing through induction of RNA interference. siRNAs can be allowed for in
      vitro and in vivo applications. siRNAs have been successfully studied in vitro,
      but little is known about its efficacy in vivo. We have successfully applied the
      siRNA technique for silencing glucose transporter 3 in cultured L6 muscle cells.
      The siRNA technique has been used efficiently to silence RasGRP4 expression in
      mast cells.

PMID- 16110168
TI  - Mast cell activation by lipoproteins.
AB  - Mast cells are activated by a number of agents that act independently from
      immunoglobulin E (IgE)-mediated hypersensitivity. One of these agents is oxidized
      low-density lipoprotein (oxLDL). OxLDL has been implicated in the pathogenesis of
      atherosclerosis and has been shown to induce microvascular dysfunction by the
      activation of mast cells. In this chapter, we describe the method for isolation
      of human LDL, oxidation of LDL, and demonstrate that oxLDL activates mast cells
      by measuring messenger ribonucleic acid (mRNA) levels and protein levels of
      interleukin (IL)-8 an inflammatory cytokine. IL-8 is a potent chemoattractant for
      neutrophils and monocytes, which would result in a chronic inflammatory response.
      IL-8 mRNA levels were measured by reverse-transcription polymerase chain reaction
      and protein levels by enzyme-linked immunoassay.

PMID- 16110169
TI  - Mast cell activation by stress.
AB  - Mental or emotional stress has been shown to cause mast cell degranulation in
      several different tissues. Several lines of experimental evidence indicate that
      stress, working through the sympathetic nervous system, or the hypothalamus
      pituitary-adrenal axis, stimulates peripheral nerves to release neuropeptides
      that bind to receptors on the mast cells, causing them to degranulate. In order
      to investigate the effects of stress on mast cell degranulation, it is necessary
      to first establish a reproducible animal model of stress (in this case, rat) and
      also to ensure that the control animals do not show any signs of stress. This
      procedure requires a great deal of care and attention because the methods used by
      many institutions to house laboratory rodents, do in fact cause them stress. This
      topic is addressed in this chapter. In addition, two histological techniques are
      described to visualize connective tissue and mucosal mast cells and to assess
      their degree of degranulation.

PMID- 16110170
TI  - In vivo models for studying mast cell-dependent responses to bacterial infection.
AB  - Mast cells are a critical component of host defense against bacterial infections.
      Activation of these cells during infection induces both innate and adaptive
      aspects of protective immunity needed for the elimination of the bacteria and
      survival of the host. These functional roles for the mast cell have been
      principally characterized using two in vivo models of acute bacterial infection
      featuring Gram-negative pathogens such as Escherichia coli. Here, we present
      basic protocols for the identification of mast cell-dependent biological
      functions during bacterial infection. These include the use of mast cell
      deficient mice, the identification of mast cells in tissue, the culture of
      uropathogenic E. coli, and the basic analysis of mast cell-dependent functions in
      the peritoneal cavity and footpad models of bacterial pathogenesis.

PMID- 16110171
TI  - Bacterial activation of mast cells.
AB  - Mast cells often are found in a perivascular location but especially in mucosae,
      where they may response to various stimuli. They typically associate with
      immediate hypersensitive responses and are likely to play a critical role in host
      defense. In this chapter, a common airway pathogen, Moraxella catarrhalis, and a
      commensal bacterium, Neiserria cinerea, are used to illustrate activation of
      human mast cells. A human mast cell line (HMC-1) derived from a patient with mast
      cell leukemia was activated with varying concentrations of heat-killed bacteria.
      Active aggregation of bacteria over mast cell surfaces was detected by scanning
      electron microscopy. The activation of mast cells was analyzed by nuclear factor
      kappaB (NF-kappaB) activation and cytokine production in culture supernatants.
      Both M. catarrhalis and N. cinerea induce mast cell activation and the secretion
      of two key inflammatory cytokines, interleukin-6 and MCP-1. This is accompanied
      by NF-kappaB activation. Direct bacterial contact with mast cells appears to be
      essential for this activation because neither cell-free bacterial supernatants
      nor bacterial lipopolysaccharide induce cytokine secretion.

PMID- 16110172
TI  - Activation of mast cells by streptolysin O and lipopolysaccharide.
AB  - This chapter provides protocols to measure the reversible permeabilization of
      mast cells by streptolysin O (SLO) and to follow SLO-induced activation of mast
      cells by monitoring degranulation, activation of mitogen-activated protein
      kinases, and production of tumor necrosis factor-alpha. A method that uses SLO to
      deliver molecules into the cytosol of living cells also is described.
      Furthermore, we outline a procedure to measure the activation of nuclear factor
      kappaB by lipopolysaccharide and ionomycin using transfection of mast cells with
      reporter genes by electroporation. These protocols should be widely applicable in
      mast cell research.

PMID- 16110173
TI  - Mast cell apoptosis.
AB  - Apoptosis is a physiological form of cell death. Cells undergoing apoptosis
      execute a genetically controlled program that leads to organized breakdown of
      cellular structures and ends in phagocytosis of their remains. In mast cells,
      several mechanisms regulating apoptosis have been identified including growth
      factors, tumor necrosis factor-alpha receptors, monomeric IgE, Toll-like
      receptors, and proteins of the bcl-2 family. Methods used to characterize
      apoptosis of mast cells are reviewed, with special attention to flow cytometric
      analysis of annexin V staining, analysis of deoxyribonucleic acid fragmentation
      by gel electrophoresis and end-labeling techniques, measurement of caspase
      activity by enzymatic assays, and characterization of pro- and anti-apoptotic
      proteins by immunoblotting.

PMID- 16110174
TI  - Detection of esophageal varices in liver cirrhosis using non-invasive parameters.
AB  - AIM: recent guidelines recommend that all cirrhotic patients without previous
      variceal hemorrhage undergo endoscopic screening to detect esophageal varices.
      The aim of this study is to evaluate clinical, laboratory and ultrasound
      parameters to detect esophageal varices. METHODS: this is a cross sectional
      study. Fourty seven consecutive cirrhotic patients without history of variceal
      hemorrhage underwent upper endoscopy. Physical examination, laboratory and
      ultrasonography to find portal vein diameter and anterioposterior splenic
      measurement of each patient were also recorded. RESULTS: esophageal varices was
      detected in 36 of the 47 patients (76.6%). Using bivariate analysis we found that
      a platelet count of 82,000/ul (90.9% sensitivity; 41.7% specificity), portal vein
      diameter of 1.15 cm (75% sensitivity; 54.5% pecificity) and an anteroposterior
      splenic measurement of 10.3 cm (83.3% sensitivity; 63.6% specificity) were
      predictive factors for esophageal varices in liver cirrhosis. CONCLUSION: our
      data show that platelet count, portal vein diameter and anteroposterior splenic
      measurement can be used as non invasive parameters to detect esophageal varices
      in cirrhotic patients.

PMID- 16110175
TI  - Recurrent hypoglycemia in pancreatic-type diabetes mellitus and Grave disease
      patient.

PMID- 16110176
TI  - Geripause and its clinical implications.

PMID- 16110177
TI  - Lymphomatous cells in pleural effusion.

PMID- 16110178
TI  - The use of capecitabine in cancer: management of the hand foot syndrome.

PMID- 16110179
TI  - Atherogenic dyslipidemia and the metabolic syndrome.

PMID- 16110180
TI  - Proteolytic enzymes from generative organs of flowering plants (Angiospermae).
AB  - Pollen proteases were discovered over 100 years ago, whereas the enzymes from
      female tissues have been used since the Roman era in simple biotechnological
      processes. In the last decade a great progress has been made in studies on plant
      proteases, including those from the generative organs. This paper reviews reports
      published in the last decade, concerning purification, properties and
      localization of proteases from generative parts of flowering plants against the
      background of the general proteolytic machinery of the plant. Special attention
      is paid to differences in protease structure and properties in comparison to
      other enzymes from the same catalytic classes. Participation of the proteases in
      all steps of pollen-pistil interaction as well as in pollen tube growth is
      discussed. Further intensive studies with use of native substrates are necessary
      to understand the role of proteases in pollination.

PMID- 16110181
TI  - Genetics of durable resistance to leaf rust and stripe rust of an Indian wheat
      cultivar HD2009.
AB  - The Indian bread wheat cultivar HD2009 has maintained its partial resistance to
      leaf rust and stripe rust in India since its release in 1976. To examine the
      nature, number and mode of inheritance of its genes for partial leaf rust and
      stripe rust resistance, this cultivar was crossed with cultivar WL711, which is
      susceptible to leaf rust and stripe rust. The F1, F2, F3 and F5 generations from
      this cross were assessed separately for adult plant disease severity under
      artificial epidemic of race 77-5 of leaf rust and race 46S119 of stripe rust.
      Segregation for rust reaction in the F2, F3 and F5 generations indicated that
      resistance to each of these rust diseases is based on 2 genes, each with additive
      effects. Although the leaf rust resistance of HD2009 is similar in expression to
      that conferred by the gene Lr34, but unlike the wheats carrying this gene,
      cultivar HD2009 did not show leaf tip necrosis, a morphological marker believed
      to be tightly linked to the leaf rust resistance gene Lr34. Thus, the non
      hypersensitive resistance of HD2009 was ascribed to genes other than Lr34.

PMID- 16110182
TI  - The influence of several factors on the efficiency of androgenesis in carrot.
AB  - The influence of cultivar, donor plant and culture procedure on the efficiency of
      androgenesis was studied in carrot anther culture. Experiments were carried out
      on five carrot cultivars: CxC 9900 F1, Lucky B F1, HCM, Beta III and Perfekcja,
      which were chosen because of their high carotene contents. Two procedures of
      anther culture were compared: (1) incubation in darkness for two weeks, followed
      by exposure to continuous light and transfer onto a fresh medium of the same
      composition; and (2) incubation in darkness until embryos appeared, without
      transfer onto a fresh medium. Temperature was +27 degrees C all the time.
      Genotype played an important role in the process of androgenesis in carrot anther
      culture. The efficiency was the highest in cv. HCM - 5.6 embryos per 100 anthers.
      Considerable differences in the capacity for androgenesis were observed between
      individual donor plants. The ratio of embryos obtained per 100 anthers for cv.
      HCM varied from 0.0 to 48.9. The second procedure of anther culture proved to be
      more efficient, cheaper and less complicated.

PMID- 16110183
TI  - Genetic variability among beech (Fagus sylvatica L.) populations from the Sudety
      Mountains, in respect of peroxidase and malate dehydrogenase loci.
AB  - Individual trees growing in five populations of European beech (Fagus sylvatica
      L.) in the Sudety Mountains were investigated in respect of variability of
      peroxidases (2 loci) and malate dehydrogenase (1 locus). Differences between
      populations were illustrated by a dendrogram constructed on the basis of
      Hedrick's (1974) genetic distances. The mean GST coefficient (=0.0333) value
      demonstrated the higher level of intra-population variability, as compared to the
      inter-population (DST = 0.0149) variability.

PMID- 16110184
TI  - Genetic studies on collar rot resistance in opium poppy (Papaver somniferum L.).
AB  - The collar rot disease has been reported recently and occurs at the 10-12-leaf
      stage of plants of opium poppy. Infected plants topple down and dry prematurely
      due to fast rotting at the collar region. The inoculum for this study was
      multiplied on the cornmeal-sand culture. Genetic ratios were calculated by the
      chi-square test. Inheritance studies on this disease show a monogenic pattern of
      segregation with the ratio of 3 : 1 at F2, 1 : 2 : 1 at F3 and 1 : 1 at the
      backcross. Such genetic ratios clearly indicate that a single recessive gene (rs
      1) is responsible for disease resistance in opium poppy. The inference drawn on
      the basis of the present study will be a great help in the future breeding
      programme of opium poppy for collar rot resistance.

PMID- 16110185
TI  - MspI polymorphisms in the 3rd intron of the swine POU1F1 gene and their
      associations with growth performance.
AB  - The study aimed to compare MspI polymorphisms in the 3rd intron of the porcine
      gene encoding the pituitary-1 transcription factor (Pit-1, renamed as POU1F1)
      among 5 breeds and to determine the associations between its genotypes and growth
      performance in a commercial pig population by using the PCR-RFLP technique.
      Significant differences in genotypic and allelic frequencies were found between
      the meat-type and fat-type breeds (P < 0.05), and between miniature pigs and
      others (P < 0.05). No breed deviated from the Hardy-Weinberg equilibrium
      (verified by chi-square test). The general linear model analysis revealed that
      higher body weight on day 180 (BW180) and average daily gain (ADG) were
      significantly associated with POU1F1 DD genotype (P < 0.05). The differences in
      BW180 and ADG between DD pigs and both CD and CC pigs were significant (P <
      0.05), and the DD pigs had a significantly higher body weight on day 45 (BW45)
      and on day 70 (BW70) than CC pigs (P < 0.05). All measured growth traits, except
      for body weight at birth (BWB), showed higher values in DD pigs. The D allele had
      a favorable positive effect on growth traits. Thus POU1F1 is a potential major
      gene or marker for growth traits.

PMID- 16110186
TI  - Genetic differentiation induced by selection in an inbred population of the
      silkworm Bombyx mori, revealed by RAPD and ISSR marker systems.
AB  - Artificial selection has been widely utilized in breeding programmes concerning
      the commercially important silk-producing insect Bombyx mori. Selection increases
      the frequency of homozygotes and makes homozygous effects stronger. Molecular
      variation induced by selection in the inbred population of B. mori strain
      Nistari, was assessed in terms of genic differentiation by using a polymorphic
      profile generated by RAPD and ISSR marker systems. Artificial selection for
      longer larval duration (LLD) for 4 generations resulted in a significant
      prolongation of larval duration (F = 89.28; P = 5.14 x 10(-7)). The lines
      selected for shorter larval duration (SLD) were not significantly different from
      the control group. RAPD and ISSR primers generated polymorphic profiles when
      amplified with genomic DNA of individuals of LLD and SLD lines. Distinct markers
      specific to LLD individuals were observed from the 3rd generation and indicated
      selection-induced differentiation of allelic variants for longer larval duration.
      Both SLD and LLD were characterized by high gene diversity (h approximately equal
      to 0.197) and total heterozygosity (Ht > or =0.26), low homogeneity (chi-square
      test, p < 0.005) as well as a large coefficient of gene differentiation (Gst > or
      =0.42) but low gene flow (Nm < or =0.42). Genetic distance was the highest
      (0.824) between 3rd generations of SLD and LLD. High heterozygosity and prolonged
      larval duration substituted for shorter larval duration (the traditional trait of
      fitness) in the Nistari LLD larvae.

PMID- 16110187
TI  - Genetic variation of Polish endangered Bilgoraj horses and two common horse
      breeds in microsatellite loci.
AB  - Genetic variation of endangered Bilgoraj horses and two common Polish horse
      breeds was compared with the use of 12 microsatellite loci (AHT4, AHT5, ASB2,
      HMS2, HMS3, HMS6, HMS7, HTG4, HTG6, HTG7, HTG10, VHL20). Lower allelic diversity
      was detected in all investigated populations in comparison to other studies.
      Large differences in the frequencies of microsatellite alleles between Bilgoraj
      horses and two other horse breeds were discovered. In all polymorphic loci all
      investigated breeds were in the Hardy-Weinberg equilibrium. Mean Fis values and
      the results of a test for the presence of a recent bottleneck were non
      significant in all studied populations. Comparable values of observed and
      expected gene diversity indicate no substantial loss of genetic variation in the
      Bilgoraj population and two other breeds. The lowest variability observed in the
      investigated group of Thoroughbred horses was confirmed. About 10% of genetic
      variation are explained by differences between breeds. Values of pairwise Fst and
      two measures of genetic distance demonstrated that Bilgoraj horses are distantly
      related to both common horse breeds.

PMID- 16110188
TI  - Detection of two nucleotide substitutions and putative promoters in the 5'
      flanking region of the ovine IGF-I gene.
AB  - The objective of this study was to search for polymorphisms and gene regulatory
      sequences in the 5' flanking region of the sheep insulin-like growth factor I
      (IGF-I) gene. PCR-SSCP analysis of the 5' flanking region revealed three banding
      patterns. Family study indicated that these patterns in mixed breed sheep
      corresponded with three genotypes (with their frequencies in parentheses) AA
      (0.70), AB (0.25), and BB (0.05), which arose from a one-locus, two allele (A, B)
      polymorphism. Genotypic frequencies in 22 purebred Polypay sheep were AA (0.77)
      and AB (0.23). Calculated frequency of the A allele in Polypays was 0.89. No
      deviation from Hardy-Weinberg equilibrium was detected in this study. Fragments
      amplified using DNA from homozygous individuals were sequenced and aligned next
      to each other. A T to C transition and a G to C transversion were found at
      positions 179 and 181, respectively, of the amplified PCR product, resulting in
      recognition sites for Bsp143II and HaeI. Analysis of a fragment of 2,162 base
      pairs upstream of Exon 1, assembled from sheep ESTs and sequence of our amplified
      PCR products, revealed a promoter sequence approximately 100 bp downstream of the
      polymorphic sites. The assembled DNA fragment shared 70% sequence homology
      between sheep and human. These results suggest that sequence of the 5' flanking
      region of IGF-I gene and location of the IGF-I promoters are similar in human and
      sheep.

PMID- 16110189
TI  - Restriction fragment length polymorphism of exon 2 Ovar-DRB1 gene in Polish Heath
      Sheep and Polish Lowland Sheep.
AB  - Exon 2 of the Ovar-DR gene is known to encode the MHC outer domain (alpha or beta
      chain) that forms the binding area to antigens presented. The study was aimed at
      analysing exon 2 Ovar -DRB1 gene polymorphism in Polish Heath Sheep and Polish
      Lowland Sheep (Zelazna variety). A total of 101 and 99 ewes of the respective
      breeds were included in this study. We identified 65 different haplotypes in
      Polish Heath Sheep and 68 in Polish Lowland Sheep. The PCR-RFLP method and PCR
      products sequencing made it possible to identify two new sequences of exon 2 Ovar
      DRB1 gene (AY230000 and AY248695). A distinct polymorphism in the exon 2 sequence
      presents possibilities for immune response toward a great variety of pathogens.

PMID- 16110190
TI  - A new PCR-RFLP within the domestic pigeon (Columba livia var. domestica)
      cytochrome b (MTCYB) gene.
AB  - A total of 244 domestic pigeons (Columba livia var. domestica) were genotyped
      using the PCR-RFLP method. A 999 bp fragment of the MTCYB gene was amplified. The
      amplification products were digested with restriction enzymes. PCR-RFLP for MvaI
      restriction enzyme was observed. Frequencies of alleles were as follows: MTCYB(C)
      -0.926, MTCYB(G)-- 0.074. The frequencies of MTCYB/MvaI alleles found in this
      study for non-homing pigeons considerably deviate from the values found for
      homing/racing pigeons (allele MTCYB(G) occurred only in the non-homing breeds).

PMID- 16110191
TI  - Genotoxicity of the volatile anaesthetic desflurane in human lymphocytes in
      vitro, established by comet assay.
AB  - The aim of the present study was to estimate the genotoxicity of desflurane,
      applied as a volatile anaesthetic. The potential genotoxicity was determined by
      the comet assay as the extent of DNA fragmentation in human peripheral blood
      lymphocytes in vitro. The comet assay detects DNA strand breaks induced directly
      by genotoxic agents as well as DNA fragmentation due to cell death. Another
      anaesthetic, halothane, already proved to be a genotoxic agent, was used as a
      positive control. Both analysed drugs were capable of increasing DNA migration in
      a dose-dependent manner under experimental conditions applied. The results of the
      study demonstrated that the genotoxicity of desflurane was comparable with that
      of halothane. However, considering the pharmacodynamics of both drugs, the
      genotoxic activity of desflurane may be connected with a less harmful effect on
      the exposed patients or medical staff.

PMID- 16110192
TI  - Genotype/phenotype correlation in a SCA1 family: anticipation without CAG
      expansion.
AB  - We report on a family with spinocerebellar ataxia type 1 (SCA1), in which the age
      at onset and the severity of the disease do not correlate with the number of CAG
      repeat units. Although a marked anticipation was observed in the proband, it was
      not a consequence of an expansion of the CAG tract. None of the expanded alleles
      contained CAT interruptions. The pathologic expansion in this family was stable
      during the paternal but not maternal transmission, where it expanded by one
      trinucleotide and unexpectedly did not lead to anticipation. Our observations
      suggest that factors other than the length of the CAG repeat play a considerable
      role in determination of the disease course.

PMID- 16110193
TI  - Genetic screening for glucocorticoid-remediable aldosteronism (GRA): experience
      of three clinical centres in Poland.
AB  - Glucocorticoid-remediable aldosteronism (GRA), also known as familial
      hyperaldosteronism type I (FH-I, OMIM 103900), is a monogenic form of inherited
      hypertension caused by the presence of a chimaeric gene originating from an
      unequal cross-over between the CYP11B1 (11beta-hydroxylase) and CYP11B2
      (aldosterone synthase) genes. The hybrid gene has the CYP11B1 sequence at the 5'
      end, including the promoter, and the CYP11B2 sequence at the 3' end. The aim of
      our study was to evaluate the prevalence of GRA in a Polish population of 129
      patients with primary hyperaldosteronism (PHA) and 132 patients with essential
      hypertension (EH), through the use of a PCR-based test revealing the chimaeric
      gene. None of our PHA or EH patients was positive for the CYP11B1/CYP11B2
      chimaeric gene. These data suggest that GRA is unlikely to be a common cause of
      hypertension in Polish subjects. However, the real prevalence of GRA in Poland,
      both in the high-risk group of individuals with primary hyperaldosteronism and in
      the general population, remains to be established.

PMID- 16110194
TI  - Subfertile couple with t(4;22)(q23;q11.2).
AB  - A couple was referred for cytogenetic examination due to idiopathic miscarriages.
      The proband proved to be a carrier of chromosomal translocation and her partner's
      karyotype was found to be normal. The karyotype of the proband is
      46,XX,t(4;22)(q23;q11.2) and can be regarded as a reason of fertility problems in
      the investigated couple. The risk of further miscarriages is high, but the risk
      of a progeny with abnormal karyotype is rather low, as the progeny would probably
      have lethal imbalances.

PMID- 16110195
TI  - Homozygote for mutation c.1204 + 1G > A of the ARSA gene presents with a late
      infantile form of metachromatic leukodystrophy and a rare MRI white matter lesion
      type.
AB  - The metachromatic leukodystrophy (MLD)--causing mutation c.1204 + 1G > A damages
      an intron-exon splice site recognition sequence. This results in a complete loss
      of enzymatic activity of arylsulfatase A (ARSA) protein molecules. We have found
      a late-infantile type MLD-patient to be homozygous for this mutation, which was
      not reported earlier, but is consistent with previous suggestions. Interestingly,
      the cerebral magnetic resonance imaging (MRI) in this patient displayed linear or
      punctuate structures radiating in the demyelinated white matter, which resembled
      the patterns described in Pelizaeus-Merzbacher disease. It should be emphasised
      that whenever a cerebral MRI demonstrates the "tigroid" or "leopard-skin"
      demyelination pattern not only Pelizaeus-Merzbacher disease, but also
      metachromatic leukodystrophy diagnosis should be considered; this suggests the
      necessity of ARSA activity estimations in patients with such specific MRI
      patterns.

PMID- 16110196
TI  - Polarization anisotropy of X-ray atomic factors and 'forbidden' resonant
      reflections.
AB  - Symmetry and physical aspects of 'forbidden' reflections excited by a local
      polarization anisotropy of the X-ray susceptibility are surveyed. Such
      reflections are observed near absorption edges where the anisotropy is caused by
      distortions of the atomic electronic states owing to interaction with
      neighbouring atoms. As a consequence, they allow for extracting nontrivial
      information about the resonant atom's local environment and their physical
      conditions. The unusual polarization properties of the considered reflections are
      helpful to distinguish them from other types of 'forbidden' reflections. When
      such reflections are excited, it is, for example, possible to determine not only
      the intrinsic anisotropy of an atomic form factor but also additional anisotropy
      induced by thermal motion, point defects and/or incommensurate modulations. Even
      the local ;chirality' of atoms in centrosymmetric crystals is accessible.
      Unsolved key problems and possible future developments are addressed.

PMID- 16110197
TI  - The algebraic approach to the phase problem.
AB  - A rather detailed report is presented on the present status of the algebraic
      approach to the phase problem in the case of an ideal crystal in order to make
      clear that some points must still be proven for it to apply to neutron
      scattering. To make this extension, the most important results that were
      previously obtained in the case of X-ray scattering are derived again by a
      different procedure. By so doing, the three-dimensional case is treated
      explicitly, the polynomial equations in a single variable whose roots determine
      the positions of the scattering centres are explicitly reported and the procedure
      is shown to generalize to neutron scattering, overcoming the difficulty related
      to the non-positivity of the scattering density. In this way, it is fully proven
      that the atomicity assumption removes the phase ambiguity in the sense that the
      full diffraction pattern of an ideal crystal can uniquely be reconstructed from a
      suitable finite portion of it in both X-ray and neutron scattering. The
      procedures able to isolate these portions that contain the pattern's full
      information are also given.

PMID- 16110198
TI  - Graph-theoretical characterization of periodicity in crystallographic nets and
      other infinite graphs.
AB  - Local automorphisms in infinite graphs are defined as those automorphisms for
      which the distance (in the graph-theoretical sense) between any vertex and its
      image possesses an upper bound. Abelian subgroups of direction-preserving local
      automorphisms without fixed point, so-called shift groups, are used to determine
      the quotient graph of infinite graphs. It is shown that the shift group, the
      closest topological analogue to a translation group in crystal structures, is
      isomorphic to the quotient group C/C(0) of the cycle space C of the quotient
      graph by some subgroup C(0), its kernel. As a main consequence, the isomorphism
      class of nets can be determined directly from their labeled quotient graph,
      without having recourse to any embedding. A general method is formulated and
      illustrated in the case of cristobalite and moganite structures. Application to
      carbon and other kinds of nanotubes is also described.

PMID- 16110199
TI  - Extended X-ray interbranch resonance concept for crystals with a one-dimensional
      deformation.
AB  - The X-ray interbranch resonance concept is extended to crystals with a one
      dimensional deformation. The original approach, which proceeds from the Lagrange
      formalism, is developed. The principle of local ;lattice homogeneity' is also
      incorporated in the resonance concept. It postulates the local translation
      symmetry by lattice spacings in the vicinity of any point of X-ray trajectories.
      In this connection, interbranch scattering is considered as the process that
      violates this principle. The new interbranch effect is predicted for a strongly
      distorted crystal with thickness of the order of the interbranch extinction
      length. In this case, the interbranch wavefield oscillations related to the
      resonance interbranch splitting are suggested for the diffraction profile.

PMID- 16110200
TI  - Electron crystallography of zeolites--the MWW family as a test of direct 3D
      structure determination.
AB  - The efficacy of direct methods for solving the crystal structures of zeolites
      from electron diffraction data is evaluated for a series of related materials,
      i.e. MCM-22, MCM-49 and ITQ-1. First, it is established by tilting experiments
      that all materials share the same MWW framework. The calcined product of a
      delaminated MCM-22 precursor, ITQ-2, also shares this framework structure within
      the limited number of stacked unit cells. For all materials, the underlying space
      group is P6/mmm where a approximately 14.21, c approximately 24.94 A. Traditional
      direct methods are useful for determining the projected structure down the
      hexagonal axis but are not very effective for finding the three-dimensional
      structure. On the other hand, maximum-entropy and likelihood approaches are
      effective for determining either 2D projections or 3D frameworks. The major
      restriction to 3D determinations by direct methods is the limited goniometric
      tilt range of the electron microscope, hence the ;missing cone' of information.
      Potential maps from the most accurate phase sets are, therefore, observed as
      continuous density envelopes to the true structure. Some improvement is found
      when the Sayre equation predicts missing amplitudes and phases but it is clear
      that better specimen preparation methods are required to include projections
      containing the c( *) axis of the reciprocal lattice.

PMID- 16110201
TI  - Polarization factors in the general case of three-wave diffraction.
AB  - The polarization properties of diffracted radiation depending on the geometry of
      three-wave configurations and spectral and polarization states of the incident
      radiation are considered on the basis of the representation of multiple
      diffraction geometry in the natural crystallographic coordinates. The analytical
      expressions, obtained earlier for the symmetric cases [Sheludko (2004). Acta
      Cryst. A60, 281-282], are extended for the general case of three-wave diffraction
      of radiation on single crystals. The problem of the description of conditions of
      inverse asymmetry of three-wave diffraction profiles is reduced to a classical
      analysis of quadratic and cubic equations.

PMID- 16110204
TI  - Effect of caries experience in primary molars on cavity formation in the adjacent
      permanent first molar.
AB  - This study sought to address the influence of a sound versus affected first
      and/or second deciduous molar on the incidence of visible caries experience in
      the adjacent permanent first molar. Clinical and questionnaire data were obtained
      from a 6-year prospective oral health screening project in Flanders, Belgium
      (Signal-Tandmobiel project), where 4,468 children (born in 1989) were examined
      annually during their primary school time. A multiple survival model allowing for
      dependent data with possible censoring was applied. The impact of timing of tooth
      emergence (determining the period at risk), gender, presence of sealants and
      reported oral hygiene habits was also considered. Cavity formation in permanent
      first molars was clearly influenced by the status of the adjacent primary
      molars;the effect of the second deciduous molar was most pronounced. Moreover, if
      both deciduous molars experienced caries and the child presented with poor oral
      hygiene, a peak in cavity formation of the permanent first molar 1-2 years after
      emergence was noticed. On the other hand, if a child presented with good oral
      hygiene, no peak was observed; caries risk increased slightly over time. No
      significant benefit from restoring primary molars could be demonstrated, possibly
      because of methodological limitations.

PMID- 16110203
TI  - Qualification of arterial stiffness as a risk factor to the progression of
      chronic kidney diseases.
AB  - BACKGROUND: Reflection pressure may influence the clinical course of chronic
      kidney diseases (CKDs). The relationship between the augmentation index (AI) and
      progression of non-diabetic CKDs was characterized. METHODS: Ninety-nine patients
      were enrolled into the study. Pulse wave form analysis was performed to determine
      AI that assesses arterial stiffness. RESULTS: In a cross-sectional study, a
      multiple regression analysis found that AI correlated positively to age and
      weight, and negatively to height and heart rate (R(2) = 0.50). Furthermore,
      echocardiography was performed in 51 patients who gave their consent. In male
      patients under angiotensin inhibition, left ventricular mass index increased as
      AI was elevated (r = 0.33, slope = 0.85 +/- 0.30 g/m(2)/%, p < 0.05, n = 23). A
      prospective study was performed in 41 patients who consented to having their
      creatinine clearance measured repeatedly. In the patients with angiotensin
      inhibition a higher basal AI resulted in a greater annual decrease in creatinine
      clearance (r = -0.52, slope = -0.43 +/- 0.14 ml/min/year/%, p < 0.01, n = 27).
      CONCLUSION: The present data indicate that AI as well as angiotensin contribute
      to the development of left ventricular hypertrophy. Furthermore, our results
      suggest that in addition to angiotensin, AI is a risk factor of progression of
      non-diabetic CKDs.

PMID- 16110205
TI  - Approximal caries increment in two cohorts of schoolchildren after
      discontinuation of a professional flossing program with chlorhexidine gel.
AB  - We have in two earlier studies evaluated the effect of professional flossing with
      chlorhexidine (CHX) gel treatment, in 4- to 7-year-old preschool children and in
      12- to 15-year-old teenagers. The mean caries reduction after 3 years was around
      40% compared to placebo gel or no gel treatment. The aim of the present
      investigation was to follow up these two clinical studies. The preschool children
      were followed up to the age of 16 years and the teenager group to the age of 19.
      Of the total number of original children, 71 and 80% were available at the age of
      16 and 19 years, respectively. At the 9-year follow-up, when the children were 16
      years old, the former CHX group had still significantly lower mean DFS than the
      control group (p < 0.05). The differences in caries increment occurred between 7
      and 12 years of age, whereas the number of new caries lesions during the next 4
      years were almost the same in the three groups. At the 4-year follow-up, when the
      teenagers were 19 years old, DFS was 6.9 in the former CHX group compared to 10.4
      in the control group (p < 0.05). The main conclusion of these two follow-up
      studies after 9 and 4 years, respectively, is that caries reductions obtained at
      the end of professional flossing with a 1% CHX gel were maintained.

PMID- 16110206
TI  - Oral sugar clearance in individuals with oral motor dysfunctions.
AB  - Feeding problems due to impaired oral motor functions resulting in prolonged
      meals are common among persons with brain damage. The aim of the present
      investigation was to study the oral sugar clearance in 16 individuals with oral
      motor dysfunction (OMD) and 16 individuals with normal oral functions (control
      group). Repeated saliva samples were collected on filter paper discs at two
      locations before and during 30 min after intake of a glucose tablet. The
      individuals with OMD had significantly higher initial glucose concentrations in
      saliva and longer glucose elimination time compared to the control group. For
      some of the subjects with OMD, sugar clearance was extremely slow. The sugar
      clearance time was positively related to the severity of drooling problems, but
      not to the degree of dysphagia. The results from this study indicate that
      individuals with OMD have an increased risk of dental caries.

PMID- 16110207
TI  - Analysis of fingernails and urine as biomarkers of fluoride exposure from
      dentifrice and varnish in 4- to 7-year-old children.
AB  - The use of fingernails and urine as biomarkers of exposure to fluoride (F) from
      fluoridated dentifrice and varnish was evaluated in twenty 4- to 7-year-old
      children, who were divided into two groups: group A (9 caries-free children) and
      group B (11 children with past caries experience). They used a placebo dentifrice
      for 28 days, fluoridated dentifrice (1,570 ppm F) for the following 28 days, and
      placebo dentifrice for an additional 28 days, then returned to their usual
      dentifrices. Group B children also received 4-week applications of a varnish
      (2.26% F) while using the fluoridated dentifrice. Urinary collections were
      performed 24 h before the use of fluoridated dentifrice and 24 h (group A) or 48
      h (group B) after. Fingernails were clipped every 2 weeks, for 26 weeks. Total F
      intake from diet and dentifrice was estimated. Fingernail F concentrations did
      not vary significantly throughout the study. Twenty-four-hour urinary F outputs
      (mean +/- SD, microg) were: 414 +/- 200 and 468 +/- 253 for placebo and F
      dentifrices, respectively (group A) and 402 +/-206, 691 +/- 345, 492 +/- 243 for
      placebo dentifrice, F dentifrice plus F varnish and F dentifrice, respectively
      (group B). The use of F dentifrice did not cause a significant increase in the
      urinary F output. However, when F varnish was used, a transitory increase in the
      urinary F output was detected (p = 0.001), returning to baseline levels in the
      last 24 h. Thus, F varnish is a safe method for topical F application even in
      children that use F dentifrice regularly. According to our protocol, urine was a
      suitable biomarker of exposure to F from dentifrice plus varnish, but not from
      dentifrice alone, while nails were not.

PMID- 16110208
TI  - Effect of titanium tetrafluoride, amine fluoride and fluoride varnish on enamel
      erosion in vitro.
AB  - This study aimed at evaluating the effect of 1 and 4% titanium tetrafluoride
      (TiF4) gels, amine fluoride (AmF) 1 and 0.25% and a fluoride varnish (FP) on the
      prevention of dental erosion. Two experimental groups served as controls, one
      with no pretreatment and another one pretreated with a fluoride-free varnish (FP
      blanco). Dental erosion was modelled using bovine enamel samples submitted to
      alternate cycles of acid exposure in citric acid and remineralization in
      artificial saliva. Calcium loss of all samples involved in the study was
      quantified by atomic absorption spectroscopy and erosion depths were estimated.
      Two samples of each experimental group were also analyzed by white light confocal
      microscopy. The cumulative erosion depth (in mum) after 72 min was: TiF4 gel 1%
      8.29 +/- 0.39; TiF4 gel 4% 8.27 +/- 0.55; AmF 1% 8.69 +/- 0.66; AmF 0.25% 8.86 +/
      0.33; FP 3.43 +/- 1.07; FP-blanco 14.86 +/- 1.59 and control 9.77 +/- 0.49. A
      statistically significant protective effect (p < or = 0.001) was found only for
      the group pretreated with the fluoride varnish. Within the limitations of an in
      vitro study it may be concluded that topical applications of the fluoride varnish
      tested have a protective effect on the prevention of dental erosion.

PMID- 16110209
TI  - Profilometric and microradiographic studies on the effects of toothpaste and
      acidic gel abrasivity on sound and demineralized bovine dental enamel.
AB  - The objective of this study was to assess the abrasive effects of toothpastes and
      acidic F gels on sound and demineralized enamel. Pairs of enamel specimens were
      cut from bovine incisors, embedded in epoxy resin and polished. An artificial
      subsurface lesion of 80-90 microm depth was created in one specimen from each
      pair. The samples were covered with adhesive tape, thereby exposing the enamel
      for abrasivity testing. All samples were divided into six groups of 15 and
      brushed with a slurry (1:3) of F gel or toothpaste and human saliva. Brushing
      with water (control) or with slurry was carried out (16,000 strokes) using a
      medium toothbrush (load 275 g) mounted in a brushing machine. Abrasion was
      evaluated using laser profilometry, and was about 50% less on sound than on
      demineralized enamel (p < 0.001). In the latter, brushing with water (0.09 +/-
      0.03 microm) or with fluoride-free gel (0.08 +/- 0.03 microm) resulted in
      negligible wear. With a medium-abrasive paste (1.76 +/- 0.85 microm) and an
      acidic F gel (2.48 +/- 0.72 microm), brushing abrasion was significantly greater
      (p < 0.001) than with a low-abrasive paste (0.84 +/- 0.38 microm). The greatest
      wear (16.6 +/- 10.8 microm) was observed with high-abrasive paste (p < 0.001),
      and here transversal microradiography revealed a complete loss of the
      pseudointact surface after brushing. In vitro formed caries-like lesions can be
      abraded (by toothbrushing) more easily than sound enamel; hence, initial white
      spot lesions should preferably be brushed with oral hygiene products of low
      abrasivity.

PMID- 16110210
TI  - Influence of laser irradiation on the constant composition kinetics of enamel
      dissolution.
AB  - The influence of 9.6 microm CO2 laser irradiation on enamel dissolution kinetics
      was investigated using a constant composition method designed for rate
      measurements of enamel dissolution as a function of depth, on a micrometer scale.
      In contrast to lower irradiation intensities (< or =1.0 J cm(-2)), which
      consistently showed reduced dissolution rates, higher fluences (energy per
      surface area) resulted in initially increased dissolution rates, which rapidly
      decreased, after dissolution times corresponding to removal of a few micrometers,
      to rates similar to those acquired using lower fluences. It was also demonstrated
      that surface damage during laser irradiation could be limited to the first 1-2
      microm by lowering the number of pulses per spot during the irradiation
      procedure. The constant composition method can be used to measure detailed
      kinetics of inhibition of acid dissolution of dental enamel that has been treated
      by low fluence 9.6-microm CO2 laser irradiation.

PMID- 16110211
TI  - Comparison of fluorescence detection of carious dentin for different excitation
      wavelengths.
AB  - This study compared the fluorescence spectra obtained at three laser excitation
      wavelengths from intact enamel, sound dentin and carious dentin. Results were
      analyzed using a figure of merit (ratio of backscattered peak to maximum
      fluorescence amplitude). The results showed that the best excitation wavelengths
      for caries detection, which offered the greatest contrast between sound and
      carious tissue, were 442 and 632 nm. A discussion of the results between these
      two ends of the visible spectrum is provided. The results confirmed the choice of
      red light as a good excitation source for fluorescence detection of caries.

PMID- 16110212
TI  - The effect of video repositioning on the reliability of light-induced
      fluorescence imaging: an in vivo study.
AB  - The ability to monitor longitudinally the development, arrest or resolution of
      early demineralised lesions is one strength of quantitative light-induced
      fluorescence (QLF). When taking sequential images of an individual's teeth for
      monitoring it has been suggested that the subsequent images should be taken from
      the same position the baseline image. To assist in this process, video
      repositioning software is available that enables automatic capture of images once
      the system identifies that they are similar enough to the baseline comparator.
      The purpose of this study was to determine if the use of such software-assisted
      capture improves the reliability of subsequent QLF analysis. 20 subjects had 34
      surfaces (buccal and occlusal) imaged by 2 examiners at baseline, and again 1
      week later using both manual and software-assisted (VidRep) systems. Analysis of
      the three key reportable values for QLF (DeltaF, lesion area, DeltaQ) suggested
      that there is no significant improvement in reliability using VidRep although
      VidRep demonstrates additional advantages above and beyond image geometry,
      relating to the speed of subsequent image analysis.

PMID- 16110213
TI  - Reproducibility of electrical caries measurements: a technical problem?
AB  - The currently available instrument for electrical detection of occlusal caries
      lesions [Electronic Caries Monitor (ECM)] uses a site-specific measurement with
      co-axial air drying. The reproducibility of this method has been reported to be
      fair to good. It was noticed that the measurement variation of this technique
      appeared to be non-random. It was the aim of this study to analyse how such a non
      random reproducibility pattern arises and whether it could be observed for other
      operators and ECM models. Analysis of hypothetical measurement pairs showed that
      the pattern was related to measurements at the high and low end of the
      measurement range for the instrument. Data sets supplied by other researchers to
      a varying degree showed signs of a similar non-random pattern. These data sets
      were acquired at different locations, by different operators and using 3
      different ECM models. The frequency distribution of measurements in all cases
      showed a single or double end-peaked distribution shape. It was concluded that
      the pattern was a general feature of the measurement method. It was tentatively
      attributed to several characteristics such as a high value censoring,
      insufficient probe contact and unpredictable probe contact. A different
      measurement technique, with an improved probe contact, appears to be advisable.

PMID- 16110215
TI  - Detection of mutA genes in transmitted strains and nontransmitted strains of
      mutans streptococci.
AB  - Our aim was to determine whether an isolate carrying one of the mutA genes was
      related to its ability to be transmitted from mother to her child. First, 200
      mutans streptococci isolates were genotyped by arbitrarily primed polymerase
      chain reaction (AP-PCR) to demonstrate transmission between 20 mother-child pairs
      and to detect the transmitted and nontransmitted strains. Then the mutacin
      structural genes mutA encoding mutacin types I, II, and III were screened by PCR.
      The results showed that all strains found to carry the mutAI gene were
      nontransmitted strains; PCR screening primers mutAII and mutAIII did not yield
      amplicons in any of the strains tested. Our data suggest that an isolate carrying
      the mutAI gene is related to reduced transmission. The low frequency of detection
      of mutAII, and mutAIII suggests that there is a high heterogeneity in the genetic
      determinants needed for the production of mutacin-like substances.

PMID- 16110214
TI  - Interactions of Streptococcus mutans glucosyltransferase B with lysozyme in
      solution and on the surface of hydroxyapatite.
AB  - Several active enzymes have been identified as components of acquired enamel
      pellicle. In the present study, the interactions of Streptococcus mutans
      glucosyltransferase B (GtfB) with lysozyme in solution and on the surface of
      hydroxyapatite (HA) beads were studied. Experiments were also performed to
      investigate whether structural differences exist between glucans formed by GtfB
      enzyme in the presence or absence of lysozyme in solution and on the surface of
      HA. Hen egg-white lysozyme (HEWL) and saliva were used as the sources of
      lysozyme; lysozyme-depleted saliva was used as control. Lysozyme activity was
      significantly reduced when adsorbed onto HA beads compared with that in solution.
      The GtfB enzyme did not affect the activity of lysozyme in solution or that of
      adsorbed lysozyme onto HA. The presence of HEWL increased GtfB activity; bovine
      serum albumin had an even greater enhancing effect. Depletion of lysozyme from
      whole saliva increased GtfB activity in solution, but not on the surface of
      saliva-coated HA. The presence of lysozyme affected the amount of glucan
      formation by GtfB, but not the structure of glucans formed in solution and on the
      surface. Therefore, the interaction of lysozyme and GtfB enzymes on HA surface
      may modulate the formation of glucan and dental plaque.

PMID- 16110216
TI  - Immunogenicity and protective efficacy of a targeted fusion DNA construct against
      dental caries.
AB  - Targeting antigens to antigen-presenting cells by fusion to cytotoxic T
      lymphocyte-associated antigen 4 (CTLA4) has been shown to be a highly efficient
      method to enhance the efficacy of DNA vaccines. The purpose of this study was to
      determine the immunogenicity and protective efficacy of the targeted fusion DNA
      construct pGJA-P, which contains the signal peptide and extracellular regions of
      human CTLA4 gene, the hinge and Fc regions of human Iggamma1 gene, the glucan
      binding domain of the Streptococcus mutans gtfB gene and the A-P fragment of the
      S. mutans pac gene, compared with the fusion DNA construct pGLUA-P, which
      contains only the glucan-binding domain of the S. mutansgtfB gene and the A-P
      fragment of the S. mutans pac gene. BALB/c mice were immunized with pGJA-P, pGLUA
      P, or pCI (vector) by the intramuscular or intranasal route. Specific anti-PAc
      and anti-GTF-I serum IgG and salivary IgA antibody responses were assessed by an
      enzyme-linked immunosorbent assay. Wistar rats were orally challenged with S.
      mutans and immunized with pGJA-P, pGLUA-P, or pCI intramuscularly or
      intranasally, and caries activity was evaluated by the Keyes method. pGJA-P
      induced accelerated and increased serum and salivary antibody responses in mice
      compared with pGLUA-P. Rats immunized with pGJA-P had significantly fewer caries
      lesions than rats immunized with pGLUA-P (p < 0.01). Thus, this study
      demonstrates that the targeted DNA construct pGJA-P can enhance both systemic and
      mucosal immunity and may be a useful strategy for improving the protective
      efficacy of anticaries DNA vaccines.

PMID- 16110217
TI  - Method to detect minimal amounts of calcium dissolved in acidic solutions.
AB  - The study describes the application of the Arsenazo III method for detection of
      minimal amounts of calcium 12.4-49.4 micromol/l in different acidic solutions
      (hydrochloric acid, oxalic acid, maleic acid, phosphoric acid, tartaric acid,
      citric acid, lactic acid and acetic acid) adjusted to pH 2.0, 2.3 and 3.0. A
      mixture of the respective calcium concentrations with distilled water served as
      control. The experiments were run with ten repeats in series. Assessment of intra
      and interassay coefficient of variation, and lower limit of quantification
      revealed that depending on the acid used, the Arsenazo III method is a reliable
      tool to quantify minimal calcium contents in acidic solutions.

PMID- 16110218
TI  - Mt 21-42: development and validation of an automatic device proposed for the
      endoscopic diagnosis of Helicobacter pylori infection and atrophic gastritis.
AB  - BACKGROUND: Gastric juice may give important clinico-pathological information,
      but measurements in this medium are difficult. In this study we present and
      validate an innovative device (Mt 21-42) performing gastric juice analyses during
      endoscopy and proposed for the endoscopic diagnosis of Helicobacter pylori
      infection and hypo/achlorhydria. METHODS: Analyses on both aqueous solutions (80
      pH buffer + 120 ammonium chloride samples) and human gastric juice were carried
      out to assess the measuring performance of Mt 21-42 on the ideal and real matrix,
      respectively. Matrix spike and manipulation tests were also performed to
      investigate the matrix effect of gastric juice and to evaluate the consequences
      of its manipulation on the measurements. Furthermore, preliminary clinical tests
      were performed to evaluate the clinical potentiality of the device. RESULTS: Mt
      21-42 showed a good measuring performance on ideal matrix (coefficient variation:
      pH = 1.3%, ammonium = 2.1%) and real matrix (coefficient variation: pH = 1.2%,
      ammonium = 1.9%). Analyses on gastric juice excluded a substantial matrix effect
      (percent recovery =96.5-98.7%) but demonstrated a significant influence of
      manipulation procedures (p < 0.05). CONCLUSIONS: Human gastric juice does not
      have a substantial matrix effect for pH and ammonium determination, but its
      manipulation may affect the measurement of these components. Mt 21-42 represents
      a precise instrument for the measurement of gastric juice and a potential
      precious tool for the endoscopic detection of H. pylori infection and
      hypo/achlorhydric conditions.

PMID- 16110219
TI  - Insulin-induced hypoglycemia stimulates gastric vagal activity and motor function
      without increasing cardiac vagal activity.
AB  - BACKGROUND/AIMS: We investigated whether increasing the efferent vagal activity
      by insulin-induced hypoglycemia would enhance gastric emptying and volumes in
      healthy subjects. METHODS: Twenty healthy volunteers (10 males) were examined
      with and without vagal stimulation by insulin-induced hypoglycemia using a
      glucose clamp technique. Stomach function was tested by drinking meat soup (0.04
      kcal ml(-1)) at a rate of 100 ml min(-1) until maximal capacity. Intragastric
      volume at maximal drinking capacity was determined by three-dimensional
      ultrasound. Respiratory sinus arrhythmia (RSA) was used as an index of cardiac
      vagal activity and plasma pancreatic polypeptide (PP) as a measure of gastric
      vagal activity, and skin conductance (SC) as a measure of sympathetic tone.
      RESULTS: Insulin-induced hypoglycaemia increased drinking capacity (p = 0.002),
      gastric emptying (p = 0.02), PP (p = 0.004) and SC (p = 0.004), while
      intragastric volume was unchanged (p = 0.7) and RSA decreased (p = 0.03).
      CONCLUSION: Enhancement of gastric vagal activity by insulin-induced hypoglycemia
      increased drinking capacity and gastric emptying similarly, resulting in an
      unchanged intragastric volume. Enhanced efferent vagal activity to the stomach
      (as measured by PP) was not associated by enhanced cardiac vagal activity (as
      measured by RSA), possibly a consequence of stress-induced sympathetic activation
      during the procedure.

PMID- 16110220
TI  - Probiotics: a new treatment for antibiotic-associated diarrhea?

PMID- 16110221
TI  - The Client Satisfaction Questionnaire: psychometric properties in a Dutch addict
      population.
AB  - AIMS: The aim of this study is to investigate psychometric properties of the
      Client Satisfaction Questionnaire (CSQ-8) in a Dutch substance abuse population.
      METHODS: The CSQ-8 and the Mental Health Thermometer (the standard Dutch
      satisfaction instrument) were sent to 927 patients of a Dutch substance abuse
      treatment centre. (response rate 28.3%; n = 262). Data were compared on several
      variables (i.e., age, gender, ethnicity, treatment type). For a subgroup of
      responders (n = 84), data were compared with pre-treatment problem severity and
      treatment need (the European Addiction Severity Index). FINDINGS: Both internal
      consistency and concurrent validity were found to be high. Only treatment type
      had significant effects on CSQ-8 satisfaction scores. Scores were negatively
      skewed. CONCLUSION: The CSQ-8 is as suitable an instrument to be used in addict
      populations, as it is in other populations.

PMID- 16110222
TI  - Group psychotherapy for opiate addicts in methadone maintenance treatment--a
      controlled trial.
AB  - A controlled trial was conducted evaluating cognitive-behavioural group
      psychotherapy as a measure to reduce concomitant drug use in methadone
      maintenance treatment (MMT). 73 opiate addicts were randomly assigned to local
      routine MMT or to routine MMT plus group psychotherapy (20 sessions over 20
      weeks). Psychotherapy was delivered by therapists according to a manual. Drug use
      (urine screen) was compared at onset of psychotherapy, end of intervention period
      (6 months after study onset), and 6 months later. Data analysis was done
      according to intention-to-treat principles. Results indicated that patients in
      the psychotherapy group (n = 41) showed less drug use than control subjects (n =
      32). This group difference was statistically significant at 6-month follow-up (p
      = 0.02). These findings underscore the usefulness of group psychotherapy in MMT.
      The delayed effect is comparable to other studies evaluating cognitive
      behavioural psychotherapy.

PMID- 16110223
TI  - Validity and reliability of the German version of the short understanding of
      substance abuse scale.
AB  - This paper presents the German version of the Short Understanding of Substance
      Abuse Scale (SUSS) [Humphreys et al.: Psychol Addict Behav 1996;10:38-44], the
      Verstandnis von Storungen durch Substanzkonsum (VSS), and evaluates its
      psychometric properties. The VSS assesses clinicians' beliefs about the nature
      and treatment of substance use disorders, particularly their endorsement of
      psychosocial and disease orientation. The VSS was administered to 160 treatment
      staff members at 12 substance use disorder treatment programs in the German
      speaking part of Switzerland. Because the confirmatory factor analysis of the VSS
      did not completely replicate the factorial structure of the SUSS, an exploratory
      factor analysis was undertaken. This analysis identified two factors: the
      Psychosocial model factor and a slightly different Disease model factor. The VSS
      Disease and Psychosocial subscales showed convergent and discriminant validity,
      as well as sufficient reliability.

PMID- 16110224
TI  - Completion of long-term inpatient treatment of drug abusers: a prospective study
      from 13 different units.
AB  - Completion of treatment is an important predictor of favourable outcome. We need
      more knowledge about predictors of completion in the inpatient psychosocial
      treatment modality. This prospective study from 13 such programmes follows a
      consecutive sample of clients (n = 307) from admission to completion/dropout.
      INSTRUMENTS: EuropASI, MCMI II, SCL-25. The mean completion rate was 40% (20
      71%), with no difference between clients with no ('debutants') or previous
      ('veterans') inpatient stays. Among 'debutants', the number of years of heroin
      use was negatively related to completion. Among 'veterans', age and amphetamine
      use were positively related, while the presence of a personality disorder and
      number of previous inpatient treatments were negatively related to completion.
      Specific strategies for involving clients with personality disorders are needed.
      After three inpatient stays, other types of treatment should be offered.

PMID- 16110225
TI  - The Swedish DOC system--an attempt to combine documentation and self-evaluation.
AB  - This article addresses the issue of how documentation can become a regular and
      competence-raising activity in treatment settings. A documentation system in
      Sweden (the DOC system) is used as an illustrative example. Two propositions are
      put forward and discussed: it is important that (1) the documentation be in
      accordance with the interests of the practitioners, and (2) that the
      documentation be used for self-evaluation, in order to enhance the practitioners'
      competence. Based on experiences using the DOC system, some general observations
      about how to implement the forms and self-evaluation are presented. Finally, some
      research prospects are outlined.

PMID- 16110226
TI  - Use of illegally acquired medical opioids by opiate-dependent patients in
      detoxification treatment.
AB  - Take-home dosages in maintenance treatment are of great therapeutic importance,
      but they include the risk of the substitute being distributed illegally. We
      reviewed the extent of consumption of illegally acquired medical opiates by 142
      opiate- or poly-addicted patients consecutively admitted to a detoxification
      ward. 76 (53.5%) of them admitted to taking illegally acquired medical opiates,
      usually methadone, at least once. The cumulative duration was 30 days (median).
      Motivation was usually due to difficulties in acquiring heroin, however one third
      reported use in an attempt at self-detoxification or as transition before
      entering maintenance treatment. Maintenance patients were usually the source of
      the opiates. The results prove the necessity of stringent conditions for take
      home dosages, and illustrate deficits in the health care system.

PMID- 16110227
TI  - A randomised clinical trial of in-patient versus combined day hospital treatment
      of alcoholism: primary and secondary outcome measures.
AB  - In Germany, the treatment system for alcoholics is predominantly in-patient (IP)
      oriented, but no randomised trials of setting effects have been conducted until
      now. We examined if detoxification treatment offered in a day clinic setting
      would lead to results comparable to the usual IP treatment. After initial IP
      detoxification, patients (n = 109) at a standard withdrawal treatment unit were
      randomly assigned to IP or day hospital groups. In both settings, identical
      psychosocial treatment was given. In this article, results of primary (percent
      days abstinent and drinks per drinking day) and secondary outcome measures
      (relapses during treatment, premature termination, additional hospitalisation
      during follow-up, percent of voluntary abstinent days and continuous abstinence)
      are reported. Outcome measures were assessed quarterly during a 1-year follow-up
      period. Patients improved significantly after both treatments, but we found no
      significant setting or setting x time interaction effects for any primary or
      secondary outcome measure.

PMID- 16110228
TI  - Influence of socio-economic status, parents and peers on smoking behaviour of
      adolescents.
AB  - With the aim of analysing the importance of psycho-social factors in predicting
      adolescents' smoking behaviour, a model of the interrelations between socio
      economic status, parents', peers' and adolescents' own smoking behaviours was
      tested. The sample consisted of 2,616 adolescents. LISREL analyses were used to
      support the model; males and females were evaluated separately. Peers' smoking is
      the strongest predictor of adolescent smoking. Parents' smoking behaviour
      influences adolescents' smoking directly, but also indirectly through the
      parents' influence on peers' smoking behaviour. Socio-economic status influences
      adolescent smoking indirectly through its influence on parents' and peers'
      smoking behaviour. Our model is significant in both males and females and
      explains 42-51% of the variance in adolescent smoking behaviour. Accentuation of
      peers' influence on adolescents' smoking behaviour without considering the
      interrelations between the influence of socio-economic status, parents and peers
      may lead us to incorrect conclusions in research as well as in prevention.

PMID- 16110229
TI  - Chemotherapy-induced emesis in elderly cancer patients: the role of 5-HT3
      receptor antagonists in the first 24 hours.
AB  - OBJECTIVE: This review highlights the need to optimize 5-HT3-receptor-antagonist
      based antiemetic therapy for elderly cancer patients, particularly during the
      first 24 h after receiving chemotherapy, based on knowledge of the
      chemotherapeutic regimen, comorbidity, polypharmacy, dosing convenience and age
      related health. BACKGROUND: The proportion of elderly people (over 65 years of
      age) in the general population is increasing. Compared with the general
      population, elderly people have a greater risk of serious diseases, such as
      cancer and cardiovascular disease. Their chemotherapy can be compromised by
      factors including comorbidity, declining organ function, polypharmacy, drug-drug
      interactions and cognitive impairments. The use of aprepitant in this elderly
      population with many concomitant medications is not discussed. Many
      chemotherapeutic regimens are highly emetogenic, and nausea and vomiting are
      rated among the most distressing side effects of chemotherapy. The emetogenic
      potential of various chemotherapy regimens is reviewed, demonstrating clear
      differences in severity and time of symptom onset. Such differences are
      particularly important during the first 24 h after administration, when control
      of emetic symptoms can help to prevent the occurrence of subsequent episodes. The
      matter is further complicated by inter-patient differences in susceptibility to
      nausea and vomiting resulting from multiple factors including gender, age and
      alcohol intake. Individual patient evaluation is essential to identify those
      patients most at risk. Elderly patients may also be particularly sensitive to the
      serious physiological and physical effects of nausea and vomiting. Education
      about symptom management needs to recognize specific learning barriers in the
      elderly, such as declining sensory perception or cognitive impairment. 5-HT3
      receptor antagonists have long been the gold standard for treating chemotherapy
      induced nausea and vomiting. Pharmacological differences between 5-HT3-receptor
      antagonists suggest the need for careful consideration of individual patient
      characteristics. Selection of the most appropriate agent will optimize antiemetic
      therapy for elderly cancer patients. CONCLUSION: Chemotherapy-induced emesis in
      elderly cancer patients needs optimal control by a 5-HT3-receptor antagonist with
      uncomplicated 24-hour efficacy and good tolerability. Choosing a 5-HT3-receptor
      antagonist with a long duration of action, low risk of drug-drug interactions and
      once-daily dosing is important to ensure effective prophylaxis against nausea and
      vomiting in the elderly and simplify management for patients with cognitive
      impairment, declining organ function and comorbidity.

PMID- 16110230
TI  - Evaluation of the nucleolar organizer regions in Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder in middle
      and late age. Ribosomal RNA (rRNA) genes are located in the nucleolus (nucleolar
      organizer regions = NORs). There are increased deposits of beta-amyloid protein
      in the brains of the patients with AD and aged individuals with Down's syndrome
      (DS). The beta-amyloid gene is located in the acrocentric chromosome 21 that is
      responsible for rRNA synthesis. Therefore, it is possible that there is a
      relationship between ribosomal genes and AD. OBJECTIVE: To investigate the
      activities of ribosomal genes of AD patients by comparing the activities of NORs
      in AD patients and healthy controls with the silver-staining method. METHODS: NOR
      surface/the total nucleus surface proportions in interphase nuclei, and silver
      stainability and satellite association (SA) of acrocentric chromosomes in the
      metaphases of cultivated lymphocytes of 20 AD patients and 20 healthy controls
      (10 elderly and 10 young) were evaluated. RESULTS: A decrease in NOR
      surface/total nucleus surface proportions has been observed in the interphase
      nucleus of AD patients when compared with elderly controls (p = 0.035). When
      compared with the sizes of Ag+ segments of acrocentric chromosomes of AD patients
      and control groups, the Ag-staining size 1 of the chromosome 22 of AD patients
      was found to be more increased than that of the young controls (p = 0.018). There
      was no statistically significant difference between AD patients and control
      groups regarding the number of Ag+ acrocentric chromosomes, Ag+ chromosome 21 and
      SA frequency (p > 0.05). It has been found that there is only a slight increase
      in the total number of chromosomes in SA in AD patients when compared with
      elderly controls (p = 0.05). CONCLUSION: The decrease in NOR surface/total
      nucleus surface proportions of AD patients may indicate a reduction in the
      activity of the ribosomal genes of these patients.

PMID- 16110231
TI  - Oral amino acids in elderly subjects: effect on myocardial function and walking
      capacity.
AB  - BACKGROUND: With advancing age the risk of developing serious nutritional
      deficiencies increases, and disturbances to the actions of insulin and insulin
      like growth factor, coupled with reduced protein/amino acid (AA) intake, impair
      protein synthesis in muscles. OBJECTIVE: To assess the effects of administering
      oral AAs on walking capacity and perceived walking impairment, isometric muscular
      strength, and myocardial function at rest and during isometric exercise. METHODS:
      One hundred elderly subjects (aged >65 years) with reduced physical activity were
      randomized to receive an oral AA mixture (12 g/day) or placebo for 3 months. At
      baseline and after 3 months of therapy we assessed physical capacity with the 6
      min walk test, and perceived physical impairment with the walking impairment
      questionnaire (WIQ); we assessed maximal isometric muscular strength of the right
      hand with a handgrip dynamometer, and left ventricular ejection fraction (LVEF)
      using quantitative two-dimensional echocardiography at rest and during acute
      overload. RESULTS: Three months of AA treatment resulted in significant increases
      in 6-min walk distance (268.8 +/- 34.9 vs. 212 +/- 40 m, p < 0.001), WIQ scores
      (distance: 68.3 +/- 12 vs. 53 +/- 14.8%, p < 0.001; speed: 72.2 +/- 14.4 vs. 52.8
      +/- 12%, p < 0.001; stairs: 98.2 +/- 24 vs. 72.4 +/- 22%, p < 0.001), and in
      maximal muscular isometric strength (20.2 +/- 2 vs. 14 +/- 2.8 kg, p < 0.001).
      Moreover, peak stress LVEF was higher during AA administration when compared to
      placebo administration (67 +/- 7 vs. 56 +/- 9%, p < 0.01). Left ventricular
      response to exercise normalized during AA administration in 24 out of 32 (75%)
      patients with abnormal LV response at baseline, whereas it remained unchanged in
      the placebo group. CONCLUSION: An oral AA supply such as that used in this study
      improves ambulatory capacity, maximal isometric muscle strength and myocardial
      ability to match an acute overload in elderly subjects without affecting the main
      metabolic parameters. These functional gains may translate into increased
      perceived walking capacity.

PMID- 16110232
TI  - Homolateral hand and foot coordination in trained older women.
AB  - BACKGROUND: Age-related deterioration in homolateral hand and foot coordination
      might be due to the combined effects of aging and a sedentary lifestyle.
      Unfortunately, there is a lack of information regarding the effects of training
      programs on coordinated inter-limb behavior with advancing age. OBJECTIVE: The
      aim of the present study was to verify differences in homolateral hand and foot
      coordination between trained and untrained older women. METHODS: Fifteen
      sedentary older women were matched in age (61-70 years) with 15 older women who
      had trained for at least 7 years with 3 one-hour sessions/week of rhythmic
      gymnastics. The subjects performed simultaneous flexions and extensions of the
      homolateral wrist and ankle in the sagittal plane at a 1:1 ratio. Two homolateral
      conditions (preferred and non-preferred limbs) were tested in two coordination
      modes: in-phase (isodirectional) and anti-phase (non-isodirectional) at three
      test frequencies (80, 120, and 180 bpm, respectively). The time of correct
      execution within a maximum of 60 s was recorded for each test condition. RESULTS:
      Sedentary older women maintained the required movements for a shorter time than
      older gymnasts, especially with increasing execution frequency and in the anti
      phase condition. Older gymnasts showed no negative effects of increasing
      frequency on coordination performance in the in-phase mode, and frequency-related
      performance decrements of lower magnitude than sedentary older women in the anti
      phase mode. CONCLUSION: The present results indicate that the beneficial effects
      of rhythm-based training can be better understood when both the spatial and
      temporal constraints of the inter-limb coordination performance are considered.
      In fact, trained women largely succeeded in maintaining temporal constraints of
      in-phase inter-limb coordination even at the highest execution frequency, whereas
      sedentary women performed worse than trained women already at the lowest
      frequency. Furthermore, only trained women still succeeded in the anti-phase
      conditions. Thus, it appears that regular and prolonged practice of rhythmic
      gymnastics enhances inter-limb performance over both a sedentary lifestyle as
      well as ageing.

PMID- 16110234
TI  - Why do older people report fewer headaches?
AB  - BACKGROUND: We have previously confirmed a clear decline in headache prevalence
      with increasing age. This parallels the pattern in other painful conditions but
      the age-related decline in prevalence is greater for headache. OBJECTIVE: To
      investigate whether the decline in headache prevalence with age was associated
      with the elimination of work-related factors, increases in other health problems
      or concomitant use of pain-relieving medicines. We discuss these and other
      possible explanations from the literature. METHODS: Cross-sectional postal survey
      to a random sample of 5,000 adults with follow-up by (i) consultations with
      general practitioners and prescriptions issued during the 12 months subsequent to
      the survey and (ii) a follow-up postal survey at 12 months. RESULTS: Headache
      prevalence was similar in working and retired respondents within age strata.
      Headache sufferers were more likely to consult their general practitioner for any
      reason (excluding headache) compared with non-sufferers and this was true for
      each age group. Headache sufferers were also more likely to be frequent
      consulters compared with non-sufferers in all except the oldest age group (age 66
      years and over) where there was no difference. There was a clear increase in
      prescriptions for analgesics and non-steroidal anti-inflammatory drugs issued
      with increasing age. There was no difference in the percentage of daily
      medication users among headache sufferers compared with non-sufferers.
      CONCLUSION: Neither retirement from work nor the presence of other health
      problems account for the decline in headache prevalence with age. Whilst the data
      on concomitant use of pain-relieving medicines suggest this is also not a major
      factor in the age-related decline, the high use of such medicines in older age
      groups means we cannot rule out a link. Evidence from the literature suggests
      that there may be a number of age-related factors involved including changes in
      reporting of headache, biochemical changes, and the development of strategies to
      prevent and manage headaches.

PMID- 16110233
TI  - Dependence of Mini-Nutritional Assessment scores with age and some hematological
      variables in elderly institutionalized patients.
AB  - BACKGROUND: Nutritional imbalance is a serious problem in developing countries,
      especially for the older population, which makes simple and rapid instruments for
      nutritional evaluation very necessary in order to have a detailed picture of the
      undernutrition epidemiology in those places. OBJECTIVE: This work aimed to
      evaluate the nutritional status of elderly institutionalized patients by use of
      the Mini-Nutritional Assessment (MNA) test and compare the MNA scores with some
      hematological variables. METHODS: We performed a cross-sectional study in elderly
      institutionalized patients (153) of all nursing homes in the Brazilian city of
      Uberlandia, using the MNA questionnaire and quantitative analysis of
      erythrocytes, hematocrit, hemoglobin, serum iron and transferrin. The subjects
      were classified by gender, nutritional state and age range. The nutritional
      categories were compared by analysis of variance and the dependence between the
      considered variables was tested with the Spearman correlation analysis. RESULTS:
      60% of the subjects were female. The average age was 74.6 +/- 9.5 and 78.5 +/-
      9.5 years for male and female individuals, respectively. 18.3% of the patients
      presented undernutrition, 45.7% presented risk of undernutrition, and 36.0% were
      well nourished. These three nutritional categories showed statistically
      significant differences among the MNA scores, age and all the hematological
      parameters, for the sum of both genders, but not for the age, iron and
      transferrin values of the male individuals and hematocrit and hemoglobin values
      of the female patients. Significant differences between genders were not observed
      only for the MNA and transferrin values. MNA values presented positive
      correlations with erythrocytes, hematocrit, hemoglobin, and serum iron levels,
      and also a negative correlation with age, which was attributed to a worsening of
      the nutritional state with age. CONCLUSION: Based on the MNA, 64% of the elderly
      institutionalized patients of Uberlandia presented risk of undernutrition and
      undernutrition, and their nutritional state is aggravating with the age increase,
      which is consistent with the age-dependent decrease observed in some
      hematological variables. Since the low MNA scores were not necessarily associated
      to subnormal mean values of the hematological variables, we can conclude that the
      low MNA values are predicting situations that still did not manifest
      pathologically in those variables.

PMID- 16110235
TI  - Orthopaedic injuries following falls by hospital in-patients.
AB  - BACKGROUND: Falls are one of the most frequent episodes on the hospital wards.
      OBJECTIVE: To identify orthopaedic injuries sustained by in-patients falling on
      the hospital wards and to find out what treatment these required along with the
      additional time and cost that this incurred. METHODS: A retrospective analysis of
      900 incident forms and case records was undertaken for a 3-year period. Fractures
      and other soft-tissue injuries sustained and time, place, and mode of injury were
      noted. Type of fractures sustained and specific treatment required including
      operative procedure needed were studied. The cost of each treatment and the total
      cost in terms of time and money were calculated. RESULTS: We identified 42
      patients with orthopaedic injuries; 53% of the falls were recorded on medical
      wards. A poor pre-fall mobility was an important factor in over 80% of the cases,
      and a variety of medical conditions pre-existed in the elderly ill patients.
      Eighteen patients (42%) sustained hip fractures, of whom 15 patients (36%)
      required surgical treatment. There were 9 deaths in total, 5 of them occurred in
      patients with hip fractures. The cost of treating the injuries amounted to about
      GBP 70,000. An additional hospital stay of 56 weeks in total was needed, most
      patients requiring between 1 and 5 weeks of additional stay. CONCLUSIONS: Falls
      in elderly in-patients can result in a variety of skeletal injuries. These may
      require major operative procedures and result in significant morbidity and can
      prove fatal. The treatment of these injuries is a substantial added expenditure
      to the trust.

PMID- 16110236
TI  - Functional disability related to diabetes mellitus in older Hong Kong Chinese
      adults.
AB  - OBJECTIVE: To investigate the associations between diabetes and disability in
      three domains and to determine whether the associations are mediated by diabetes
      related complications. DESIGN AND METHODS: A random representative sample of
      2,003 non-institutionalized older Hong Kong Chinese was interviewed. The diabetic
      status was measured by the self-reported method. Disability was assessed by
      standardized questionnaire on basic activities of daily living (ADLs),
      instrumental ADLs, and mobility. RESULTS: 12.3% of our participants reported
      having diabetes. Older adults with diabetes are more likely to report difficulty
      in 12 of 15 ADLs than older adults without diabetes. Older adults with diabetes
      are about twice as likely to report disability in higher functioning tasks only,
      as well as mobility and higher functioning tasks, and 3.5 times as likely to
      report disability in self-care tasks with or without any other mobility or higher
      functioning tasks than those without diabetes, after adjusting for age, gender,
      marital status and education. Adjustment for diabetic-related medical conditions,
      the first two associations attenuated slightly, but remained significant, whereas
      the last one became insignificant. The last results were different from what has
      been found in previous studies. CONCLUSION: Diabetes is strongly related to a
      wide range of disabilities in older Hong Kong adults and the underlying
      mechanisms might be different for different categories of disability.

PMID- 16110237
TI  - A population-based survey of factors relating to the prevalence of falls in older
      people.
AB  - BACKGROUND: Research on older people's perception regarding their quality of life
      and services and supports needed to maintain their independence was identified as
      a priority for the South Australian Department of Health in 2000-2001. This
      population survey was conducted to examine issues that older persons considered
      important in the areas of housing, transport, finances and information provision.
      OBJECTIVE: The aim of this article is to present the characteristics of community
      dwelling older adults who reported falling in the previous 12 months. METHOD: A
      random representative sample of community-dwelling adults, living in South
      Australia, and aged 65 years and over were selected based on a sample from the
      electronic white pages telephone directory. Overall, 2,619 interviews were
      conducted (70.5% response rate) using Computer-Assisted Telephone Interviewing
      technology. RESULTS: Approximately 30% of older adults had experienced a fall in
      the previous 12 months. The characteristics of people who had fallen included
      those in the older age groups, with fair or poor general health, whose health had
      worsened in the last 12 months, with lower socioeconomic status, those born in an
      English-speaking country, needing assistance at home, and with a home in need of
      repair. Of the respondents who had experienced a fall in the previous 12 months,
      71.8% did not consider that they were at risk of having another fall. CONCLUSION:
      There is a wide range of characteristics associated with community-dwelling older
      adults over the age of 65 who report falling in the previous 12 months.
      Perceptions of the risk of falling also vary. All factors need to be considered
      when targeting interventions to reduce the risk of both initial and multiple
      falls.

PMID- 16110238
TI  - Footwear characteristics and foot problems in older people.
AB  - BACKGROUND: Foot problems are common in older people, however the contribution of
      incorrectly fitting footwear and heel elevation to the development of foot pain
      and deformity has not been fully evaluated. OBJECTIVES: To examine the
      relationship between footwear characteristics and the prevalence of common
      forefoot problems in older people. METHODS: Presence of foot pain and deformity
      were identified in 176 people (56 men and 120 women) aged 62-96 years (mean
      80.09, SD 6.42) using a questionnaire and clinical assessment. Shoe fit was
      determined by comparing length, width and area measurements of shoes with foot
      measurements. Past and present use of high heels in women was documented, and
      heel elevation of footwear was measured. RESULTS: Most subjects wore shoes
      narrower than their feet. Women wore shoes that were shorter, narrower and had a
      reduced total area compared to their feet than men. Wearing shoes substantially
      narrower than the foot was associated with corns on the toes, hallux valgus
      deformity and foot pain, whereas wearing shoes shorter than the foot was
      associated with lesser toe deformity. Wearing shoes with heel elevation greater
      than 25 mm was associated with hallux valgus and plantar calluses in women.
      CONCLUSION: Incorrectly fitting footwear is common in older people and is
      strongly associated with forefoot pathology and foot pain. These findings
      highlight the need for footwear assessment in the management of foot problems in
      older people.

PMID- 16110239
TI  - An improved method for determining telomere length and its use in assessing age
      in blood and saliva.
AB  - BACKGROUND: It is disputed whether telomeres shorten with age. OBJECTIVE: The
      proposition of this study was to answer this question. METHODS: The question was
      answered by a simple method consisting of a color reaction combined with long
      term electrophoresis and weak voltage. RESULTS: The telomeres shorten and the
      shortening is much higher than previously assumed. CONCLUSION: The telomere
      theory of ageing and cancer is corroborated and for the first time it is possible
      to estimate age in blood or saliva.

PMID- 16110240
TI  - Successful treatment of deep dyspareunia and primary dysmenorrhea with
      laparoscopic uterosacral nerve ablation (LUNA) procedure.
AB  - Deep dyspareunia, often described as pain resulting from pelvic thrusting during
      sexual intercourse, is relatively common and has many causes. To date, feasible
      surgical interventions for deep dyspareunia are very rare. The two procedures
      which have been mentioned in the literature for the treatment of deep dyspareunia
      were laparoscopic uterosacral ligament ablation (LUNA) and uterine
      ventrosuspension. We report the case of a young female patient, aged 32, gravida
      3, parity 2, presenting with deep dyspareunia and primary dysmenorrhea for 4
      years. She had both subjective and objective improvements for dyspareunia and
      primary dysmenorrhea following LUNA operation. Further large-scaled randomized
      controlled trial is mandatory to verify the surgical effect of LUNA operation for
      patients with deep dyspareunia.

PMID- 16110241
TI  - Vaginal hysterectomy for the enlarged uterus.
AB  - OBJECTIVE: To evaluate the effect of uterine weight on the perioperative outcomes
      of vaginal hysterectomy for benign gynecological conditions. MATERIALS AND
      METHODS: The medical records of 312 consecutive women who underwent vaginal
      hysterectomies for benign gynecological conditions without major pelvic
      reconstruction at Temple University Hospital between March 1994 and August 1999
      were reviewed. 88 women with uterine weights > or =250 g were compared with 224
      women with uterine weights <250 g. The risk of perioperative complications,
      operative time, perioperative hemoglobin change, length of postoperative hospital
      stay, and readmission were evaluated between the groups. RESULTS: Groups were
      similar with respect to age, parity, history of previous pelvic surgery and
      concurrent adnexal removal. Operative time was significantly increased for women
      with uteri weighing > or =250 g. Women with uterine weight > or =250 g had a
      higher risk for postoperative febrile morbidity. The risks of all other major
      complications, perioperative change in hemoglobin concentration, length of stay,
      and readmission risk were not statistically different between the groups (p <
      0.05). CONCLUSIONS: Despite the increased postoperative febrile morbidity and
      prolonged operative time, women with uteri weighing > or =250 g who underwent
      vaginal hysterectomy were discharged from the hospital without any increase in
      other complications when compared to women with a smaller uterus.

PMID- 16110242
TI  - Index variables for studying outcomes in vascular cognitive impairment.
AB  - Multivariable modeling in dementia risk factor studies is limited by the number
      of factors that can be analyzed practicably. Index variables, which integrate
      exposures, can efficiently reduce dimensionality. The Consortium to Investigate
      Vascular Impairment of Cognition study, a Canadian memory-clinic-based 30-month
      cohort study of 1,347 patients, used a vascular risk factor index (from 20
      exposures) and a vascular clinical profile index (17 items). Patients with
      vascular cognitive impairment had higher index counts compared to those without
      cognitive impairment (0.16 +/- 0.11 vs. 0.07 +/- 0.07 for the risk factor index
      and 0.21 +/- 0.16 vs. 0.09 +/- 0.07 for the clinical profile index; p < 0.05).
      Both the death rate and the rate of cognitive impairment increased exponentially
      with the index variable (r > 0.90 for each index). The risk ratio for death was
      1.12 (95% CI 1.09-1.15) for each increment of the risk factor index and was 1.23
      (95% CI 1.1-1.28) for each increment of the clinical profile index. With each
      index, the areas under the receiver operating characteristic curves for
      predicting death and institutionalization ranged from 0.73 +/- 0.01 to 0.75 +/-
      0.01. Construction of index variables that integrate multidimensional factors is
      a promising approach to assessing risk in multi-determined states.

PMID- 16110243
TI  - Distal renal tubular acidosis: alkali heals osteomalacia and increases net
      production of 1,25-dihydroxyvitamin D.
AB  - In 2 women with distal renal tubular acidosis and osteomalacia, alkali treatment
      cured the bone disease and was accompanied by marked increases in the serum 1,25
      dihydroxyvitamin D concentration, without a significant change in the 25
      hydroxyvitamin D concentration.

PMID- 16110245
TI  - Association study of a functional MAOA-uVNTR gene polymorphism and personality
      traits in Chinese young females.
AB  - Monoamine oxidase A (MAOA), a mitochondrial outer membrane enzyme, degrades
      biogenic amines including norepinephrine, dopamine and serotonin, which have been
      implicated in the expression of personality traits. We tested the associations
      between functional MAOA-uVNTR genetic variants and personality traits in a cohort
      of 370 healthy young Chinese females. Subjects who were homozygous for the 4
      repeat allele of the MAOA-uVNTR gene tended to have a higher total score on the
      Harm Avoidance (HA) dimension of the Tridimensional Personality Questionnaire
      (TPQ) (p = 0.056), and had a significantly higher score on subdimension 4 of HA
      (p = 0.020) compared with the 3-repeat carriers. No significant association was
      demonstrated for MAOA-uVNTR polymorphism and the other two dimensions (Novelty
      Seeking and Reward Dependence) of TPQ. These results suggest that genetic
      variants of the MAOA gene may play a role in HA, but not in Novelty Seeking or
      Reward Dependence.

PMID- 16110244
TI  - Morphological abnormalities in nitric-oxide-synthase-positive striatal
      interneurons of schizophrenic patients.
AB  - Schizophrenia has been suggested to be a neurodevelopmental disorder, and nitric
      oxide-synthase (NOS)-positive neurons were shown to be involved in distorted
      cortical development in schizophrenia. Here we investigated whether nitrinergic
      neurons in the striatum of schizophrenic patients also display abnormalities
      regarding distribution or morphology. To do so, postmortem putaminal sections of
      schizophrenic subjects were examined by means of nicotinamide adenine
      dinucleotide phosphate diaphorase (NADPHd) staining and NOS immunohistochemistry.
      NOS-positive neurons were counted and analyzed morphologically. Abnormalities
      regarding morphology or number of NOS-containing neurons could be found in the
      putamen of schizophrenics (n = 3), but not controls (n = 5). Neurons were either
      of abnormal size and branching pattern, or they were markedly reduced (130 +/- 44
      vs. 54 +/- 62 NADPHd-positive somata/mm(3) putamen; p < 0.0001). Striatal
      nitrinergic interneurons might thus be involved in the pathogenesis of at least
      some forms of schizophrenia. Studies on larger samples are however needed to
      further corroborate this finding.

PMID- 16110246
TI  - Rapid visual information processing in schizophrenic patients: the impact of
      cognitive load and duration of stimulus presentation. A pilot study.
AB  - The inability to sustain attention has been proposed as a core deficit in
      schizophrenia. The Continuous Performance Task (AX-CPT) and the Rapid Visual
      Information Processing Task (RVP) are widely used neuropsychological tasks to
      measure sustained attention. The RVP displays numbers as stimuli, whereas the AX
      CPT uses letters. Ten patients with chronic schizophrenia and 18 healthy control
      subjects were studied using four different versions of the RVP. The versions
      differed with regard to stimulus presentation time (600 vs. 1,200 ms) and the
      number of target sequences to be memorized: either one sequence (low cognitive
      load) or two sequences (high cognitive load). Schizophrenic patients showed a
      reduced number of hits only on the task version with 600 ms stimulus duration
      coupled with high cognitive load. The combination of high cognitive load and
      short stimulus duration created a critical performance breaking point for
      schizophrenic patients. This finding supports the hypothesis that patients have
      an impaired ability to coactivate different cognitive performances; thus the
      results favor the theory of impaired functional connectivity in schizophrenia.

PMID- 16110247
TI  - G-protein beta3 subunit C825T polymorphism tends to be associated with seasonal
      variation in young male college students.
AB  - This study investigated the relationship between G-protein beta(3) subunit (GNB3)
      C825T polymorphism and seasonal variation in 189 young male college students. The
      subjects were genotyped for C825T and were evaluated by the Seasonality Pattern
      Assessment Questionnaire. The Global Seasonality Score (GSS) between the three
      genotypes revealed a marginal difference. The heterozygotes showed significantly
      higher seasonal variations in GSS than the homozygotes. The prevalence of
      heterozygotes tended to be higher in seasonals compared with normal subjects,
      although it was not statistically significant. These results suggest that GNB3
      C825T polymorphism tends to be related to seasonal variation in mood and behavior
      in the normal population.

PMID- 16110248
TI  - Paradoxical sleep in mice lacking M3 and M2/M4 muscarinic receptors.
AB  - Acetylcholine is crucial for the regulation of paradoxical sleep (PS) and EEG
      theta activity. To determine the contribution of individual muscarinic receptors
      to these events, we analyzed the sleep-waking cycle and EEG activities of mice
      lacking functional M(3) or M(2)/M(4 )receptors. Daily PS amounts were
      significantly decreased in M3-/- (-22%) but not in M2/M4-/- mice. Further, the
      theta peak frequency for PS was significantly increased in both M2/M4-/- and M3-/
      mice. This study supports the potential role of M(3) rather than M(2) and M(4)
      muscarinic receptors in the modulation of PS in mice and strengthens the idea
      that multiple muscarinic receptors contribute to the regulation of the EEG theta
      activity during PS.

PMID- 16110251
TI  - Active carboxypeptidase B is present in free form in serum from patients with
      acute pancreatitis.
AB  - BACKGROUND: Active carboxypeptidase B (aCAP) is the main product of activation of
      procarboxypeptidase. The other product derived from procarboxypeptidase B
      (proCAP), the activation peptide carboxypeptidase B (CAPAP), has been shown to be
      a marker for severity in acute pancreatitis. There have been relatively few
      studies dealing with the role of this enzyme in acute pancreatitis. METHODS: A
      double-antibody ELISA for immunoreactive aCAP (ir-aCAP) was developed, and ir
      aCAP was determined in the serum of patients with acute pancreatitis and
      characterized using gel filtration. RESULTS: Serum from healthy individuals
      contained minimal levels of ir-aCAP, while serum from 25 patients with acute
      pancreatitis contained between 0.6 and 158 nmol/l. Gel filtration of serum
      samples from patients with acute pancreatitis showed the presence of two peaks of
      ir-aCAP, one corresponding to the molecular size of the free active enzyme and
      one corresponding to cross-reactive proCAP. When pure aCAP was mixed with serum
      in vitro, all ir-aCAP was recovered as one peak of free enzyme. No
      immunoreactivity disappeared or changed in molecular size, as might be expected
      if the active enzyme was bound to an inhibitor. CONCLUSION: aCAP is present in
      free form in the circulation of patients with acute pancreatitis.

PMID- 16110250
TI  - Role of inflammation in pancreatic carcinogenesis and the implications for future
      therapy.
AB  - BACKGROUND: The link between inflammation and pancreatic cancer has been observed
      for a number of gastrointestinal neoplasms. This review examines the role of
      inflammation in pancreatic carcinogenesis and how it can be utilised to develop
      new therapies against pancreatic cancer. METHODS: A literature review of Pubmed,
      Medline and Web of Science databases was undertaken using the key words,
      pancreatic cancer, inflammation, inducible nitric oxide, interleukins, pro
      inflammatory cytokines, cyclooxygenase-2, NF-kappa B, reactive oxygen species,
      DNA adducts, lipoxygenases, chemoprevention. RESULTS: Epidemiological evidence
      and molecular studies both in vitro and in vivo all support the hypothesis that
      inflammation plays an important in the initiation and progression of pancreatic
      tumours. CONCLUSION: Sustained damage caused by chronic inflammation may precede
      the onset of frank malignancy by a significant interval. As such, suppression of
      inflammatory changes and oxidative damage, may help delay or even prevent the
      inception of pancreatic neoplasia.

PMID- 16110252
TI  - Delayed gastric emptying and intestinal hormones following pancreatoduodenectomy.
AB  - BACKGROUND/AIMS: Delayed gastric emptying (DGE) is frequently reported in
      patients following pancreatoduodenectomy (PD). The present study tested the
      hypothesis that gastrointestinal hormones known to effect gastric emptying
      contribute to DGE in patients after PD. METHODS: Patients with (delayed, n = 9)
      or without clinical signs of DGE (non-delayed, n = 22) after PD were
      investigated. Plasma concentrations of motilin, glucagon-like peptide-1 (GLP-1),
      neurotensin, and peptide YY (PYY) and the gastric emptying rate (GER), assessed
      by the paracetamol absorption method were measured after a liquid meal on
      postoperative day 11. RESULTS: Days with a nasogastric tube (p < 0.01), days
      until solid food was tolerated (p < 0.05), and hospital stay (p < 0.001) were
      increased in delayed compared to non-delayed patients. The total and incremental
      integrated peptide responses of motilin and GLP-1 were similar, but the responses
      of neurotensin and PYY were reduced, in delayed compared to non-delayed patients,
      whether considered on clinical grounds or by measured GER (p < 0.05-0.005).
      CONCLUSION: Neurotensin and PYY slow the rate of gastric emptying in humans.
      Therefore, our findings suggest that reduced hormone responses were the
      consequence of DGE arising from delayed delivery of nutrients to the distal
      intestine where the endocrine cells secrete neurotensin and PYY reside.

PMID- 16110253
TI  - Duodenopancreatectomy versus duodenum-preserving pancreatic head excision for
      chronic pancreatitis.
AB  - BACKGROUND: The aim of this study was to compare two surgical procedures in the
      treatment for chronic pancreatitis (CP): pancreatoduodenectomy resection
      (classical Whipple - PD procedure, or pylorus-preserving - PPPD) to duodenum
      preserving pancreatic head excision with longitudinal pancreatojejunoanastomosis
      (DPPHE/PJA), to define the advantages of each procedure with regard to
      postoperative complications, pain relief, and the quality of life. MATERIAL AND
      METHOD: 104 consecutive patients were included into this study.
      Duodenopancreatectomy was chosen when the head pancreatic mass was present or
      pancreatic cancer could not be ruled out (48 patients); otherwise DPPHE/PJA was
      performed (56 patients). Quality of life was measured prospectively on two
      occasions, before the procedure and during follow-up (median 39 months after
      surgery) using the European Organization for Research and Treatment of Cancer
      (EORTC) Quality-of-Life Questionnaire (QLQ-C30). The test was re-evaluated for
      patients suffering from CP. Pain intensity was quantified using a specially
      designed pain score. Early postoperative morbidity and mortality were assessed
      and evaluated in both groups of patients. RESULTS: Total pain score decreased
      significantly after surgery in both groups of patients. During the follow-up
      period, the global quality of life improved by 30.4% in the DPPHE/PJA group, and
      by 23.2% in the PD/PPPD group. Postoperative morbidity and mortality were higher
      in the resection group, but the differences were not significant. CONCLUSIONS:
      Both surgical procedures led to significant improvement in the quality of life
      and pain relief after surgery for CP. The EORTC QLQ-C30 was found to be a valid
      and readily available test for quality-of-life assessment in patients with CP.

PMID- 16110254
TI  - Clinical significance of bacterial cultures from 28 autologous islet cell
      transplant solutions.
AB  - PURPOSE: Total pancreatectomy and autologous islet cell transplantation are being
      investigated as a novel surgical treatment for patients with chronic
      pancreatitis. Preliminary data has demonstrated the presence of enteric bacteria
      in solutions used to harvest islet cells. Subsequently, we started culturing
      autologous islet solutions to determine whether any concordance existed between
      these cultures and postoperative infectious complications. METHODS: A
      retrospective analysis evaluated microbiologic cultures between July 2000 and
      November 2003; 33 patients underwent total or completion pancreatectomy and islet
      cell transplantation. Five patients were excluded due to incomplete culture data.
      Aerobic, anaerobic and fungal cultures were performed on all islet preparation
      solutions. Patient charts were examined for postoperative infectious
      complications. Microbiologic data from these infections was compared to
      pretransplant islet cultures. Islet cells from each patient were tested in
      vitrofor both function and viability. RESULTS: Of the 28 patients, 25 (89.3%) had
      bacterial culture-positive media solutions. Only 4 patients (14.3%) had an
      infectious complication from which bacteria was isolated that corresponded to
      bacteria in their islet cell preparation. In vitro islet cell viability was
      greater than 95% in the pretransplant aliquots. CONCLUSION: These results suggest
      that transplantation of bacterial-positive islet cell solutions does not appear
      to increase the risk of postoperative infectious complications or impact islet
      cell viability. Therefore, prolonged antibiotic treatment against these specific
      bacteria beyond the perioperative period does not seem warranted.

PMID- 16110255
TI  - Predictive value of heparanase expression in the palliative therapy of pancreatic
      cancer.
AB  - BACKGROUND/AIMS: Patients with pancreatic ductal adenocarcinoma (PDA) have a
      median survival of less than six months from diagnosis. Palliative chemotherapy
      with the current standard gemcitabine does only marginally improve median
      survival. There may be subgroups of patients receiving palliative therapy that
      have a better prognosis. Factors predicting response to palliative therapy are
      ill-defined, though. Heparanase, an endoglycosidase degrading components of the
      extracellular matrix, promotes cell invasion, is involved in angiogenesis and
      plays a role in tumor metastases. It is expressed in PDA and its expression is
      associated with shorter postoperative survival after pancreatic resections.
      METHODS: 58 patients with inoperable PDA were treated with gemcitabine therapy.
      Tissue sections from primary or metastatic tumor were used for
      immunohistochemical analysis. Heparanase expression was determined and correlated
      to tumor response, time to progression and survival. RESULTS: Heparanase
      expression was detectable by immunohistochemistry in 36 out of 58 (62%) patients
      analyzed. Overall survival was 7.4 vs. 13.3 months (p = 0.006) in heparanase
      positive and -negative tumors, respectively. Progression-free survival was 1.3
      vs. 3.4 months, respectively (p = 0.47). CONCLUSION: Heparanase expression may be
      a useful marker to predict response to palliative therapy with gemcitabine in
      PDA.

PMID- 16110256
TI  - An evidence-based approach to the diagnosis and staging of pancreatic cancer.
AB  - Technology has revolutionized the diagnosis and staging of pancreatic malignancy.
      Previously, staging of disease was accomplished by exploratory laparotomy. Now,
      however, tumor size, lymph node and vascular involvement and the presence of
      metastases can be reliably assessed prior to operation using a widely available
      series of diagnostic tests, facilitating a preoperative assessment of tumor
      resectability. Appropriate use of these tests often spares patients with
      unresectable disease the need for operative intervention. As part of our staging
      algorithm we routinely employ a combination of clinical suspicion, a high
      resolution helical CT scan and a serum CA 19-9 level. Endoscopic ultrasonography
      is useful in the patient in whom CT findings are equivocal, or in whom a tissue
      diagnosis is desired. Laparoscopy is reserved for patients with suspected
      advanced disease despite imaging findings to the contrary. Using this strategy,
      pancreatic malignancy may be diagnosed as expeditiously and as cost-effectively
      as is possible given current technology.

PMID- 16110257
TI  - Clinical perspectives in pancreatology: compliance with acute pancreatitis
      guidelines in Germany.

PMID- 16110258
TI  - Lactobacilli in necrotizing pancreatitis.

PMID- 16110259
TI  - TRAIL cleaves caspase-8, -9 and -3 of AM-1 cells: a possible pathway for TRAIL to
      induce apoptosis in ameloblastoma.
AB  - Tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL/Apo-2L), a potent
      ligand in inducing apoptosis, has recently emerged as a novel anticancer agent
      based on its ability to induce apoptosis in tumor cells, while exhibiting no
      toxicity in most normal cells. Since no potent apoptosis-inducing factor has been
      found yet in ameloblastoma, the present study was conducted. In the present
      study, expressions of TRAIL receptors, death receptor 4 (DR4) and DR5, were
      detected in all ameloblastoma tissues by immunohistochemistry as well as in AM-1
      cells by immunofluorescence. By applying TRAIL in AM-1 cells, ameloblastoma cell
      line, for 24 h, we found that TRAIL cleaved caspase-8, -9 and -3, and lowered
      mitochondrial membrane potential (Deltapsim), and markedly induced apoptosis in
      AM-1 cells (46%). These results suggested that TRAIL is a potent apoptosis
      inducing ligand in ameloblastoma.

PMID- 16110260
TI  - Transcription factors GATA-4 and GATA-6, and their potential downstream effectors
      in ovarian germ cell tumors.
AB  - Ovarian germ cell tumors (GCTs) are histologically heterogeneous neoplasms
      originating from activated germ cells, the oocyte stem cells. These rare tumors
      often contain many different tissues mixed together, and malignant components are
      occasionally hidden within benign tissues thus complicating the diagnosis. The
      reasons for the variable differentiation of germ cells are still largely unknown.
      As transcription factors GATA-4 and GATA-6 as well as their downstream factors
      (e.g. HNF-4, BMP-2 and Ihh) are essential for normal yolk sac development, we
      studied their expression in 19 ovarian GCTs. Endodermal markers were expressed
      distinctively in different GCT types. The malignant endoderm in yolk sac tumors
      expressed all factors of endodermal development included in the study.
      Dysgerminomas, on the contrary, expressed only GATA-4 and, in a minority of
      cases, Ihh and BMP-2. The results suggest that GATA-4 and GATA-6 detected in the
      ovarian GCTs have retained their normal function. The fact that GATA-6 and HNF-4
      are expressed exclusively in endodermal tissues indicates that these
      transcription factors play a role in the differentiation of germ cells towards
      the endodermal phenotype. Analysis of the nuclear transcription factors in tumor
      tissue could serve as a new informative diagnostic tool for ovarian GCTs.

PMID- 16110261
TI  - Early and late changes in vestibular neuronal excitability after deafferentation.
AB  - Medial vestibular nucleus neurons develop a sustained increase in
      electrophysiological excitability after deafferentation, which may be an
      important component of 'vestibular compensation' (the behavioural recovery that
      follows peripheral vestibular lesions). We investigated the effects of gamma
      aminobutyric acid, glutamate and glycine receptor blockade on the spontaneous
      activity of deafferented medial vestibular nucleus neurons in slices, to
      determine whether changes in synaptic inputs contribute to their increased
      excitability. Soon after deafferentation (4 h after labyrinthectomy) synaptic
      blockade had no effect on the elevated in-vitro firing of medial vestibular
      nucleus neurons, while later (48 h, 1 week), synaptic blockade reduced the
      elevated activity to normal. Intrinsic mechanisms therefore appear to mediate the
      elevated excitability of medial vestibular nucleus cells initially after
      deafferentation. Subsequently, changes in the efficacy of synaptic inputs are
      implicated, presumably involving intranuclear projections that are preserved in
      slices.

PMID- 16110262
TI  - Intermittent individual housing increases survival of newly proliferated cells.
AB  - In this study, we analyzed how intermittent individual housing with or without a
      running wheel influenced corticosterone levels and survival of newly proliferated
      cells in the dentate gyrus of the hippocampus. Female Balb/c mice, in standard or
      enhanced housing, were divided into groups that were individually housed with or
      without running wheels on every second day. Intermittent individual housing
      without, but not with, running wheels increased survival of proliferated cells in
      the dentate gyrus as compared with continuous group housing in standard or
      enhanced conditions. Thus, changes in housing conditions on every second day can,
      under certain circumstances, have an impact on the survival of newly proliferated
      cells in the dentate gyrus.

PMID- 16110263
TI  - Prolactin-induced activation of STAT5 within the hypothalamic arcuate nucleus.
AB  - Prolactin signalling within hypothalamic areas associated with the control of
      fertility was examined in male and lactating female rats. Following exogenous
      prolactin treatment, phosphorylation of STAT5 (signal transducer and activator of
      transcription) within the arcuate nucleus was measured using a highly sensitive
      immunoblotting strategy. A significant increase in phosphorylated STAT5 was
      detected in the arcuate nucleus of female rats compared with same-sex controls.
      No such effect was apparent in the males. Phosphorylation of STAT5 was not
      observed in the liver of either males or females. These results show that
      prolactin-induced intracellular signalling within the hypothalamus involves
      activation of the Janus tyrosine kinase/signal transducer and activator of
      transcription pathway, and that this signalling mechanism can be readily
      triggered in lactating females where prolactin receptors are known to be
      upregulated and fertility impaired.

PMID- 16110264
TI  - Event-related potentials show configural specificity of global form processing.
AB  - Glass patterns are a type of moire created when a random-dot field is overlaid
      with a rotated, translated or dilated copy. The overall form of the moire cannot
      be detected using local processing mechanisms, and because of this, Glass
      patterns are useful probes of global form processing. Here, we use event-related
      potentials to show that certain global organizations (concentric structure
      created by rotation and radial structure produced by dilation) produce much
      larger brain responses than others (linear structure created by translation). The
      results are consistent with the existence of specialized form processing
      mechanisms in the extrastriate cortex.

PMID- 16110265
TI  - Cerebral acetylcholine esterase activity in mild cognitive impairment.
AB  - Mild cognitive impairment may be an early clinical manifestation of Alzheimer's
      disease, but there are also patients who remain stable or remit. In-vivo
      measurements of cortical acetylcholine esterase activity by positron emission
      tomography have shown that it is reduced in Alzheimer's disease, and we
      investigated whether there is also a reduction in mild cognitive impairment. A
      significant reduction was observed in three of eight patients, and a significant
      association was found with progression to Alzheimer's disease within 18 months.
      These results suggest that low cortical acetylcholine esterase activity may be an
      indicator of impending dementia in patients with mild cognitive impairment.

PMID- 16110266
TI  - ERP correlates of lexical analysis: N280 reflects processing complexity rather
      than category or frequency effects.
AB  - In the context of language processing, the N280 is an anterior negative event
      related potential profile associated with the lexical categorization of
      grammatical function words versus content words. Subsequent studies suggested
      that this effect was related to word statistics including length and frequency in
      the lexicon. The current research tests the hypothesis that the N280 effect is
      related to an index of grammatical complexity. We recorded event-related
      potentials during a sentence reading task. Comparing content versus function
      words revealed the classic N280. Within function words, we compared the relative
      pronouns 'qui' and 'que' (which are identical for length and frequency) that in
      French indicate a subsequent simple (subject-subject) and complex (subject
      object) relative clause, respectively. A left anterior N280 effect was observed
      only for 'que', supporting our hypothesis that the N280 reflects grammatical
      complexity that can be confounded with lexical category and statistical
      properties.

PMID- 16110267
TI  - Glial fibrillary acidic protein and vimentin expression in the frog olfactory
      system during metamorphosis.
AB  - In the present study, we investigated glial cell organization in the olfactory
      system of adult and tadpole Xenopus laevis using glial fibrillary acidic protein
      and vimentin antibodies. Our results showed for the first time that glial
      fibrillary acidic protein was strongly expressed at the level of the olfactory
      nerve from tadpole to adult and was likely to be expressed by ensheathing glia.
      In the olfactory bulb, the nerve layer was stained, and no staining was observed
      in glomeruli. By contrast, vimentin decorated radial glia in the bulb but faintly
      stained the olfactory nerve. Interestingly, glial fibrillary acidic protein and
      vimentin presented complementary staining patterns, with glial fibrillary acidic
      protein being expressed in the peripheral olfactory system and vimentin being
      expressed in the central part of the olfactory system.

PMID- 16110268
TI  - Processing of highly novel auditory events in children and adults: an event
      related potential study.
AB  - In this study, the neural mechanisms of novelty detection in children and adults
      were examined by means of novelty-elicited event-related potentials. The gross
      morphology of the event-related potentials elicited by complex, novel stimuli was
      similar in children and adults, suggesting that processing of novel acoustic
      information is essentially similar across the age groups. The more frontally
      distributed P3 components and the larger late frontal negativities in children
      than in adults suggest an age-related change in activity in the frontal part of
      the brain. This is consistent with the findings showing that the structural
      maturation of the frontal cortex does not appear to be completed until late
      adolescence.

PMID- 16110269
TI  - Recovery of binocular responses after brief monocular deprivation in kittens.
AB  - Monocular deprivation induces a rapid ocular dominance change in the developing
      visual cortex. The early phase of the change is supposed to be labile and
      stabilized later by consolidation processes. To test the stability of early
      ocular dominance change, we examined whether binocular responses of cortical
      neurons can recover after a brief monocular deprivation in anesthetized and
      paralyzed kittens in which ocular dominance plasticity does not operate. After
      the 24-h monocular deprivation, most cortical neurons lost their responses to the
      deprived eye. The deprived eye responses, however, recovered following 2-3 days
      interval under anesthetized and paralyzed conditions. Visual stimulation did not
      facilitate the recovery. These results suggest that the early phase of ocular
      dominance plasticity is labile and declines passively.

PMID- 16110270
TI  - Age-dependent changes in distribution of P3a/P3b amplitude and thickness of the
      cerebral cortex.
AB  - With increasing age, the electrophysiological event-related potentials P3a/P3b
      tend to get a more frontal maximum. The cognitive significance of this so-called
      frontal shift is not known, but hypotheses have focused on changes in the
      integrity of the frontal lobes. The aim of the present study was to test how the
      thickness of the cerebral cortex is related to the frontal shift. Well screened
      elderly participants went through a visual three-stimuli oddball-task, a battery
      of neuropsychological tests and magnetic resonance imaging scans. It was found
      that participants with frontocentral maxima had a thicker cerebral cortex in
      distinct areas than participants with parietal maxima, both for P3a and for P3b,
      while the parietal P3b participants had a thicker cortex in the anterior
      cingulate. This is the first study to demonstrate that age-dependent changes in
      the scalp distribution of electrophysiological activity are related to
      differences in thickness of the cerebral cortex.

PMID- 16110271
TI  - Brain morphometry using diffusion-weighted magnetic resonance imaging:
      application to schizophrenia.
AB  - Loss of cortical gray matter is accompanied by a commensurate increase in the
      sulcal and intraventricular cerebrospinal fluid volume. On diffusion-weighted
      magnetic resonance imaging, this would be reflected as a higher apparent
      diffusion coefficient in affected brain regions. On the basis of the above
      premise, we suggest that the apparent diffusion coefficient may be used as a
      surrogate marker for the assessment of regional brain volume deficits. We
      demonstrate this approach by voxelwise analysis of registered apparent diffusion
      coefficient images from a group of 15 patients with schizophrenia and 15 age
      matched healthy controls. We found widespread regional apparent diffusion
      coefficient increases in patients. Affected areas included the bilateral insular
      cortex, hippocampus, temporal lobe, and occipital areas. These results largely
      concur with previous findings of cortical volume deficits in schizophrenia.

PMID- 16110272
TI  - Albumin protects cultured cerebellar granule neurons against zinc neurotoxicity.
AB  - In this study, we have investigated the role of albumin in zinc-induced
      neurotoxicity of cultured rat cerebellar granule neurons. ZnCl2 induces
      cerebellar granule cell death in a time- and concentration-dependent manner and
      albumin in serum affords a significant protection against zinc-induced
      neurotoxicity. We further measured intracellular zinc concentrations in the
      presence or absence of albumin. The results showed that exogenously added ZnCl2
      induced an increase in intracellular zinc concentrations in a concentration
      dependent fashion in albumin-free buffer. However, in the presence of albumin, it
      dramatically decreased ZnCl2-induced elevation of intracellular zinc
      concentrations. These results indicate that albumin protects against zinc-induced
      neurotoxicity by blocking extracellular zinc uptake by neurons.

PMID- 16110273
TI  - Cumulative blood oxygenation-level-dependent signal changes support the 'time
      accumulator' hypothesis.
AB  - We studied time-related changes in the blood oxygenation-level-dependent signal
      during a time reproduction task. Nine healthy study participants retained and
      reproduced stimuli of varying durations in the multi-second range. During the
      encoding phase of the task, activity in the left dorsolateral prefrontal cortex
      inversely correlated with the interval duration, while an adjacent region in the
      dorsolateral prefrontal cortex showed positive correlation with duration in the
      reproduction phase. Cumulative signal increase during the reproduction phase, as
      found in the primary motor and supplementary motor areas, may also reflect the
      time-sensitive behavior. Signal accumulation in the right caudate nucleus is in
      agreement with presumed role of basal ganglia in time perception. These results
      support the 'time accumulator' hypothesis.

PMID- 16110274
TI  - Education-associated cortical glucose metabolism during sustained attention.
AB  - Despite research suggesting that education may mitigate cognitive sequelae of
      neural injury, little is known about interactions between education and regional
      brain function. We examined whether educational experience is associated with
      relative glucose metabolism in brain regions that are important for sustained
      attention and learning. Fourteen healthy adults, with 12-18 years of schooling,
      underwent positron emission tomography scanning with 18F-fluorodeoxyglucose
      during an auditory continuous discrimination task. Years of education correlated
      positively with relative glucose metabolism in the lingual gyri (bilaterally),
      left posterior cingulate gyrus, and left precuneus. Previously, these structures
      have shown early impairment in dementia. Further investigation should explore
      whether metabolic changes in these regions contribute to the possible protective
      effect of education on cognition.

PMID- 16110275
TI  - Changes in gene expression of Zif, c-fos and cyclooxygenase-2 associated with
      spinal long-term potentiation.
AB  - Spinal cord long-term potentiation is often studied as a model for cellular
      memory of nociceptive information. In the present report, extracellular single
      unit recordings and quantitative real-time reverse transcriptase polymerase chain
      reaction were used to examine whether the induction of spinal cord long-term
      potentiation involves changes in expression of Zif, c-fos and cyclooxygenase-2.
      The data demonstrated that induction of spinal cord long-term potentiation was
      associated with a transient increase in the expression of Zif at 120 min (p <
      0.05, long-term potentiation group vs. control group). In contrast, a decrease or
      no changes were observed in the expression of c-fos and cyclooxygenase-2. The
      transient increase of the expression of Zif is consistent with an involvement in
      the transition from the early to the late-phase of spinal cord long-term
      potentiation.

PMID- 16110276
TI  - Figure-ground segregation requires two distinct periods of activity in V1: a
      transcranial magnetic stimulation study.
AB  - Discriminating objects from their surroundings by the visual system is known as
      figure-ground segregation. This process entails two different subprocesses:
      boundary detection and subsequent surface segregation or 'filling in'. In this
      study, we used transcranial magnetic stimulation to test the hypothesis that
      temporally distinct processes in V1 and related early visual areas such as V2 or
      V3 are causally related to the process of figure-ground segregation. Our results
      indicate that correct discrimination between two visual stimuli, which relies on
      figure-ground segregation, requires two separate periods of information
      processing in the early visual cortex: one around 130-160 ms and the other around
      250-280 ms.

PMID- 16110277
TI  - Cocaine abuse elevates alpha-synuclein and dopamine transporter levels in the
      human striatum.
AB  - Direct protein interactions between the dopamine transporter and alpha-synuclein
      demonstrate that dopamine uptake function is modulated by alpha-synuclein. We
      report here that chronic cocaine abuse results in an increase in alpha-synuclein
      expression in the human striatum. Immunoblot analysis in the ventral putamen
      showed that alpha-synuclein protein was increased in striatal synaptosomes from
      cocaine users compared with age-matched drug-free controls. [H]-Dopamine
      transporter uptake was increased in parallel with 2beta-carbomethoxy-3beta-(4
      fluorophenyl)tropane binding to the dopamine transporter. The increase in alpha
      synuclein protein was more marked in the ventromedial sectors of the striatum
      than in the dorsal caudate nucleus. These results demonstrate concomitant
      regulation of alpha-synuclein and dopamine transporter binding and function in
      human striatal synaptic terminals isolated from cocaine abusers. Overexpression
      of alpha-synuclein may play a role in cocaine-induced plasticity and regulation
      of dopamine synaptic tone.

PMID- 16110278
TI  - Spinal cord glia activation following peripheral polyinosine-polycytidylic acid
      administration.
AB  - Effects of repeated intraperitoneal injections of polyinosine-polycytidylic acid
      on spinal cord cells were analysed. After each injection, the number of ED-1
      microglia significantly increased in rat spinal cords. Expression of endothelial
      monocyte-activating polypeptide II, however, was not observed. The morphology of
      microglia indicated an incomplete activation state even after three repeated
      polyinosine-polycytidylic acid injections. Astrocyte activation was observed
      after the first injection using glial fibrillary acidic protein staining.
      Simultaneously with glia activation, hyperalgesia was observed, but the
      expression of P2X4 receptor, which is considered to be closely associated with
      hyperalgesia, on microglia was not detected. In sum, our data suggest that
      repeated peripheral injections of polyinosine-polycytidylic acid might alert the
      central nervous system through limited activation of microglia and astrocytes.

PMID- 16110279
TI  - Anxiety and attentional bias for threat: an event-related potential study.
AB  - We investigated the attentional bias for threat in selected high and low trait
      anxious participants using an event-related potential technique. A modified cue
      target paradigm was adopted with threatening and nonthreatening pictures as
      uninformative location cues. In high anxious individuals, reactions were speeded
      up and the occipitoparietal P1 amplitude was enhanced when targets appeared at
      the same location as threatening pictures relative to nonthreatening ones,
      whereas in low anxious individuals, the P1 amplitude tended to be enhanced when
      the targets appeared at the opposite location to threatening pictures. These
      results suggest that the attentional bias caused by peripheral threatening
      stimuli is able to modulate the visual inputs in early processing stages, and
      this mechanism is markedly influenced by an individual's anxiety level.

PMID- 16110280
TI  - Cerebellar infarction affects visual search.
AB  - Recent studies have discussed the role of the cerebellum in not only motor but
      also cognitive functions, and in particular, fronto-executive operations. Similar
      to a previous study on hemineglect patients, we recorded eye movements during a
      visual search task to investigate patients with isolated infarction of the
      cerebellum compared with controls. Patients showed longer search durations,
      associated with mild saccadic dysmetria, longer single fixation durations and a
      higher number of repeated fixations of items. Systematic search strategies were
      preserved, but less frequent in patients. In conclusion, though basic mechanisms
      of visual search including spatial memory were not affected by cerebellar
      lesions, patients' search behaviour was slower and less efficient, indicating a
      mild deficit of visual attention and motor planning.

PMID- 16110281
TI  - Preattentive discrimination of across-category and within-category change in
      consonant-vowel syllable.
AB  - Event-related potentials to infrequently presented spoken deviant syllables /pi/
      and /po/ among repetitive standard [see text] syllables were recorded in Thai
      study participants who ignored these stimuli while reading books of their
      choices. The vowel across-category and within-category changes elicited a change
      specific mismatch negativity response. The across-category and within-category
      change discrimination of vowels in consonant-vowel syllable was also assessed
      using the low-resolution electromagnetic tomography. The results of low
      resolution electromagnetic tomography mismatch negativity generator analysis
      suggest that the within-category change perception of vowels is analyzed as the
      change in physical features of the stimuli, thus predominantly activating the
      right temporal cortex. In contrast, the left temporal cortex is predominantly
      activated in the across-category change perception of vowels, emphasizing the
      role of the left hemisphere in speech processing already at a preattentive
      processing level also in consonant-vowel syllables. The results support the
      hypothesis that a part of the superior temporal gyrus contains neurons
      specialized for speech perception.

PMID- 16110282
TI  - Organization of sequential sounds in auditory memory.
AB  - A repeating five-tone pattern was presented at several stimulus rates (200, 400,
      600, and 800 ms onset-to-onset) to determine at what temporal proximity the five
      tone repeating unit would be represented in memory. The mismatch negativity
      component of event-related brain potentials was used to index how the sounds were
      organized in memory when participants had no task with the sounds. Only at the
      200-ms onset-to-onset pace was the five-tone sequence unitized in memory. At
      presentation rates of 400 ms and above, the regularity (a different frequency
      tone occurred every fifth tone) was not detected and mismatch negativity was
      elicited by these tones in the sequence. The results show that temporal proximity
      plays a role in unitizing successive sounds in auditory memory. These results
      also suggest that global relationships between successive sounds are represented
      at the level of auditory cortices.

PMID- 16110283
TI  - A study of the effects of lorazepam and dextromethorphan on the response to
      cortical 1 Hz repetitive transcranial magnetic stimulation.
AB  - We studied the effects of lorazepam and dextromethorphan on the responses to 1 Hz
      repetitive transcranial magnetic stimulation applied to the left human motor
      cortex. Lorazepam, dextromethorphan or placebo was administered to 45 normal
      controls in a double-blind fashion 2.5 h before the repetitive transcranial
      magnetic stimulation procedure. Motor cortical excitability was measured with
      single transcranial magnetic stimulation pulses before and after 15 min of 1 Hz
      repetitive transcranial magnetic stimulation applied at supra-threshold
      intensity. 1 Hz repetitive transcranial magnetic stimulation resulted in a
      decrease in motor cortical excitability in the placebo group but not in the
      groups taking lorazepam or dextromethorphan. These results suggest that cortical
      responses to 1 Hz repetitive transcranial magnetic stimulation are dependent on
      activity at both gamma-aminobutyric acid and N-methyl-D-asparate receptor
      systems.

PMID- 16110284
TI  - Signaling pathways of hypocretin-1 actions on pyramidal neurons in the rat
      prefrontal cortex.
AB  - We have investigated the direct excitatory effects of hypocretin-1 on acutely
      isolated prefrontal cortical pyramidal neurons and explored the signaling
      mechanisms of these actions. Puff application of hypocretin-1 caused an
      excitation in the recorded neurons. These effects of hypocretin-1 were abolished
      by a phospholipase C inhibitor D609, demonstrating that phospholipase C mediates
      the actions of hypocretin-1. A specific protein kinase C inhibitor,
      bisindolylmaleimide II, blocked the excitatory actions of hypocretin-1,
      suggesting that protein kinase C plays a key role. Finally, protein kinase A
      inhibitor applied intracellularly did not affect the responses. These results
      indicate that hypocretin-1 excites prefrontal neurons by activation of
      phospholipase C and protein kinase C pathways, but not protein kinase A.

PMID- 16110285
TI  - Prediction of early and late recurrence in patients with breast carcinoma.
AB  - BACKGROUND: The clinical course of patients with recurrent breast carcinoma
      varies greatly. Better characterization of an individual's clinical course for
      recurrent patients may aid in their clinical management. However, less attention
      has been paid to evaluating factors associated with the timing of recurrence in
      those patients. We investigated the clinicopathological indicators that
      determined the timing of recurrence by univariate and multivariate analysis.
      METHODS: We retrospectively examined data on 1428 curatively treated Japanese
      patients who had been surgically treated for breast cancer between 1983 and 2002.
      From these, 244(17.1%)who had clearly died of recurrence were entered into this
      study. RESULTS: By univariate analysis, tumor size, estrogen receptor(ER), and
      progesterone receptor(PgR)were significantly correlated with time to recurrence.
      Multivariate analysis indicated that the time between operation and recurrence
      was independently influenced by ER and PR. CONCLUSIONS: Our research shows that
      ER and PgR are independent factors influencing the timing of recurrence of breast
      carcinoma after curative resection. The combined analysis of these independent
      factors facilitates prediction of the time to recurrence for each patient.

PMID- 16110286
TI  - Postoperative prognosis of node-negative breast cancers predicted by gene
      expression profiling on a cDNA microarray of 25,344 genes.
AB  - BACKGROUND: In Japan, postoperative relapse occurs within five years in 9.2 to
      16% of patients whose breast cancers have not metastasized to lymph nodes at the
      time of initial surgery(node-negative, n0). Attempts to find molecular markers
      able to classify n0 breast cancers in terms of postoperative prognosis have not
      been successful. METHODS: To identify molecular indicators of prognosis for this
      type of cancer, we used a cDNA microarray consisting of 25,344 human genes to
      investigate expression profiles of 12 primary breast cancers from patients whose
      tumors recurred within five years after surgery(5Y-R) and 12 from patients who
      survived disease-free for more than five years (5Y-F). RESULTS: Sets of genes
      characterizing each group in terms of expression patterns in the tumors were
      selected by Mann-Whitney and random-permutation tests: these panels included 21
      genes expressed highly in 5Y-R tumors than in 5Y-F tumors, and 37 with higher
      expression in the 5Y-F group than in the 5Y-R group. CONCLUSIONS: We established
      a scoring system to prediction of postoperative prognosis which was 100% accurate
      as to the actual clinical outcomes of the 24 cases and therefore might be useful
      for predicting prognosis of n0 breast cancers in a clinical setting. The
      prognostic score system clearly separated the two groups without any overlap, and
      accurately predicted prognosis in 6 additional cases. Moreover, the extensive
      list of tumor-related genes identified in these experiments provides valuable
      information about progression of breast cancer and suggests potential target
      molecules for therapy of n0 breast cancers.

PMID- 16110287
TI  - Isolation and transplantation of highly purified autologous peripheral
      CD34+progenitor cells: purging efficacy, hematopoietic reconstitution following
      high dose chemotherapy in patients with breast cancer: results of a feasibility
      study in Japan.
AB  - BACKGROUND: High-dose chemotherapy with autologous stem cell support may have
      some therapeutic impact on certain groups of the patients with advanced breast
      cancer(BRCA). Since stem cell contamination by tumor cells might contribute to
      relapse, development of a tumor cell purging technique would improve the clinical
      outcome. The present study was undertaken to evaluate the purging efficacy of
      autologous mobilized CD34+peripheral stem cells in patients with breast cancer
      (BRCA) in an advanced stage or relapse. METHODS: CD34+cells were selected from
      autologous peripheral blood stem cells (PBSC) using a clinical scale of magnetic
      activated cell sorting system (CliniMACS), followed by high-dose chemotherapy
      with transplantation of CD34+ selected cells. Amplification of cytokeratin 19
      (CK19) and 20 (CK20) gene in leukapheresis products were measured to evaluate the
      performance of tumor cell elimination. RESULTS: Seven patients were entered into
      this study. After leukopheresis, 1 patient was dropped form this study due to
      poor mobilization. Among 6 patient, a total of 8 CD34+ selection was performed.
      The median purity and recovery rate of the CD34+ cells post selection was 85.1%
      (range 62.5-98.1%) and 74.2% (range 50.2-90.2%), respectively. After isolation of
      CD34+cells, the elimination rate in the logarithmic transformation of CK19 was
      2.77 log, and that of CK20 were 2.43 log and 2.53 log. In 4 patients, high-dose
      chemotherapy was performed, followed by the transplantation of the isolated
      CD34+cells. Rapid neutrophil recovery, as well as platelet recovery was seen with
      a median time to reach 0.5 x 109/l neutrophils of 9 days(range 8-9), and 20 x
      109/l platelets of 12 days (range 10-13). There was no treatment related death
      and no serious adverse events directly associated with the selection procedure or
      infusion of selected cells. CONCLUSIONS: The present study demonstrated that the
      CliniMACS system is a highly effective positive selection method and that a high
      purging efficacy could be obtained without compromising the hematopoietic
      reconstitution capacity of the graft in BRCA patients undergoing high-dose
      chemotherapy.

PMID- 16110288
TI  - Clinical and pathological features of glycogen-rich clear cell carcinoma of the
      breast.
AB  - BACKGROUND: Twenty cases of invasive ductal carcinoma of the breast with a pure
      or partial glycogen-rich clear cell carcinoma(GRCC)component are reported. GRCC
      of the breast is composed almost entirely of polygonal cells with clear
      cytoplasm. These contain large amounts of partly water-soluble glycogen. METHODS:
      The cases were analyzed using various parameters, including age at presentation,
      tumor size, tumor grade, axillary lymph node and Her2/neu status. RESULTS:
      Between 1990 and 2004, 723 patients with primary breast carcinomas were treated
      and clinicopathologic analysis was performed. 20 cases were identified as GRCC
      among the 723 cases. The patients' age at presentation ranged from 33 to 68 years
      (mean, 52 years). Tumor size ranged from 1 to 6.5 cm (mean, 2.6 cm); 35% (7 of
      20) of cases that underwent axillary dissection had positive lymph nodes. Among
      15 of 20 cases who were followed for 1-72 months, 5 cases died from their breast
      carcinoma within 5 years following the diagnosis. CONCLUSION: Our series included
      more small size carcinomas than did previous series. Lymph node status does not
      appear to be markedly different from that of the usual invasive ductal
      carcinomas. Her2/neu expression was similar to that found in common breast
      carcinomas.

PMID- 16110289
TI  - The impact of bilateral breast cancer on the prognosis of breast cancer: a
      comparative study with unilateral breast cancer.
AB  - BACKGROUND: The clinical significance of bilateral breast cancer is unclear and
      its influence on prognosis is controversial. We assessed the impact of
      synchronous and metachronous bilateral breast cancer on the prognosis compared
      with unilateral breast cancer. METHODS: Between January 1, 1960 and December 31,
      2001, 1,214 women were treated for primary operable breast cancers. Thirteen
      (1.1%) had synchronous bilateral breast cancer; 33 (2.7%) had a metachronous
      contralateral breast cancer. We compared age at operation, menopausal status,
      clinical stage, tumor size and histology, lymph node status, hormone receptor
      status, and use of adjuvant chemotherapy or hormone therapy, and we analyzed the
      impact of these factors on recurrence and survival in the 46 patients with
      bilateral breast cancer and the 1,168 patients with unilateral breast cancer.
      RESULTS: The 5-and 10-year disease-free survival rates, respectively, were 65%
      and 65% in metachronous cases, 85.7% and 64.3% in synchronous cases, and 77.9%
      and 72.1% in unilateral cases. There was no significant difference in overall
      survival among the three groups. On multivariate analysis, metachronous
      bilaterality, tumor size, lymph node status and adjuvant hormone therapy were
      each independent risk factors for recurrence, whereas bilaterality of breast
      cancer did not influence overall survival. CONCLUSIONS: Our data suggest that
      metachronous bilateral breast cancer is associated with shorter disease-free
      survival than synchronous bilateral or unilateral breast cancer, although overall
      survival does not differ among the 3 groups. Patients with metachronous bilateral
      breast cancer should be followed particularly closely in order to detect
      recurrence early and maximize quality of life.

PMID- 16110290
TI  - Probability of axillary lymph node metastasis when sentinel lymph node biopsy is
      negative in women with clinically node negative breast cancer: a Bayesian
      approach.
AB  - BACKGROUND: Although sentinel lymph node biopsy(SLNB)is highly accurate in
      predicting axillary nodal status in patients with breast cancer, it has been
      shown that the procedure is associated with a few false negative results. The
      risk of leaving metastatic nodes behind in the axillary basin when SLNB is
      negative should be estimated for an individual patient if SLNB is performed to
      avoid conventional axillary lymph node dissection(ALND). METHODS: A retrospective
      analysis of 512 women with T1-3N0M0 breast cancer was conducted to derive a
      prevalence of nodal metastasis by T category as a pre-test(i.e., before
      SLNB)probability and to examine potential confounders on the relationship between
      T category and axillary nodal involvement. Probability of nodal metastasis when
      SLNB was negative was estimated by means of Bayes' theorem which incorporated the
      pre-test probability and sensitivity and specificity of SLNB. RESULTS: Axillary
      nodal metastasis was observed in 6.1% of T1a-b, 25.1% of T1c, 28.7% of T2, 35.0%
      of T3 tumors. Point estimates for the probability of nodal involvement when SLNB
      was negative ranged from 0.3-1.3% for T1a-b, 1.6-6.3% for T1c, 2.0-7.5% for T2,
      and 2.6-9.7% for T3 tumors with representative sensitivities of 80%, 85%, 90% and
      95%, respectively. The risk may be higher when the tumor involves the upper outer
      quadrant of the breast, while it may be lower for an underweight woman.
      CONCLUSIONS: The probability of axillary lymph node metastasis when SLNB is
      negative can be estimated using a Bayesian approach. Presenting the probability
      to the patient may guide the decision of surgery without conventional ALND.

PMID- 16110291
TI  - Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes
      in breast cancer.
AB  - BACKGROUND: Sentinel lymph node biopsy using a vital dye is a convenient and safe
      method to assess lymph node status in breast cancer. However, intensive training
      is necessary to obtain a satisfactory detection rate and to avoid false-negative
      results. This paper presents a novel method using indocyanine green fluorescence
      imaging to detect sentinel lymph nodes. METHODS: Fluorescence images were
      obtained using a charge coupled device camera with a cut filter as the detector,
      and light emitting diodes at 760 nm as the light source. When indocyanine green
      was injected around the areola, subcutaneous lymphatic channels draining from the
      areola to the axilla were visible by fluorescence within a few minutes. The
      sentinel lymph node was then dissected by fluorescence navigation. RESULTS:
      Sentinel lymph node biopsy using the present method was performed on eighteen
      patients. Subcutaneous lymphatics were detectable by fluorescence in all
      patients, and sentinel nodes were successfully identified in 17 of 18 cases
      (detection rate:94%). It was possible to detect the lymphatic channels and nodes
      receiving indocyanine green with higher sensitivity by the fluorescence signal
      than by the green color. CONCLUSION: Sentinel node biopsy guided by indocyanine
      green fluorescence imaging is a promising technique for further clinical
      exploration.

PMID- 16110292
TI  - Ultrasound Demonstration of Mammographically Detected Microcalcifications in
      Patients with Ductal Carcinoma in situ of the Breast.
AB  - BACKGROUND: Breast microcalcifications are difficult to depict by ultrasound
      (US). However, recent advances in US equipment and the refinement of breast
      imaging techniques have improved the detection and characterization of small
      breast lesions. The present study attempts to determine whether US examination is
      able to demonstrate nonpalpable breast lesions associated with mammographically
      detected microcalcifications without mass density or distortion, and to evaluate
      the clinical reliability of US-guided procedures, especially in cases of ductal
      carcinoma in situ(DCIS)of the breast. METHODS: The subjects consisted of 73
      patients with breast cancer diagnosed preoperatively as DCIS by stereotactic core
      needle biopsies, all of whom had microcalcifications without other abnormalities
      on mammography. The radiological appearance and size of the clustered
      microcalcifications were evaluated. US examinations were performed
      preoperatively, and the detection rates were assessed. Sonographically detected
      lesions underwent US-guided wire localization followed by surgical excision.
      RESULTS: The lesions associated with microcalcifications were identified
      sonographically in 54 of 73 cases (74%), and the pathological examination
      revealed breast cancer in all of the corresponding specimens. Lesions with linear
      branching shape, segmental-linear distribution and category-5 calcifications on
      mammography had a high level of visibility on US. The US visible cases had a
      larger size of calcified area on mammography when compared with US invisible
      cases. Pathologically, the lesions were more frequently seen on US in cases with
      minimally invasive cancer or with comedo type DCIS. CONCLUSIONS: US examination
      is an effective method for identifying and localizing breast microcalcifications,
      and can be used as an alternative to stereotactic localization in selected
      patients with early breast cancer.

PMID- 16110293
TI  - Two cases with long-term disease-free survival after resection and radiotherapy
      for solitary brain metastasis from breast cancer with extensive nodal metastases.
AB  - Two rare cases, each with a solitary brain metastasis from breast cancer with
      extensive nodal metastases as the first site of distant metastasis, were locally
      treated with surgery and irradiation. The outcome of the two treated cases
      indicated an excellent and non-recurrent post-therapeutic survival period of more
      than 3 and 8 years, respectively. In a 50-year-old woman (Case 1), a solitary
      brain metastasis was found to have developed after standard radical mastectomy
      and adjuvant chemotherapy with doxorubicin and tegafur-uracil (UFT) and hormonal
      therapy with tamoxifen for left breast cancer. The brain metastasis was treated
      twice surgically followed by radiotherapy. One year and 6 months later, local
      recurrence of the brain metastasis appeared and was treated surgically again. No
      other treatment was done thereafter. Since then, no other distant or lymph node
      metastasis occurred, and to date her outcome has been non-eventful for 8 years
      and 5 months. In a 63-year-old woman (Case 2), a solitary brain metastasis was
      found to have developed after standard radical mastectomy and adjuvant
      chemotherapy with cyclophosphamide, epirubicin and fluorouracil (CEF) for right
      breast cancer. The brain metastasis was treated locally with surgery and
      irradiation of 50 Gy. She thereafter received no further treatments. Since then
      neither distant metastases nor local recurrence have developed, and to date the
      post-treatment outcome has been uneventful for 37 months. Our findings suggest
      that patients who developed a solitary brain metastasis as the first site of
      distant metastasis from breast cancer have a chance of achieving long-term
      disease-free survival when treated with aggressive local therapy, even in the
      presence of extensive lymph node metastases at the primary surgery site for
      breast cancer.

PMID- 16110294
TI  - Pathological complete response to trastuzumab and paclitaxel in a patient with
      inflammatory local recurrence following breast conserving surgery.
AB  - We encountered a case of inflammatory local recurrence of breast cancer after
      breast conserving surgery which attained pathological CR after combination
      therapy with trastuzumab and paclitaxel. The patient was a 49-year-old
      premenopausal woman whose left breast cancer(T2N0M0)was treated by breast
      conserving surgery (Bp+Ax). The pathological diagnosis was scirrhous carcinoma,
      g, ly1, v0, t2, n0, ER (-), PgR (+) and stage I A. Postoperatively, the residual
      breast was treated by 50 Gy irradiation followed by hormone therapy(Tamoxifen
      citrate+LH-RH analog). At 26 months after the surgery, local recurrence developed
      as inflammatory breast cancer. As the recurrent tumor was confirmed to be HER2
      positve (3+ by IHC), combination therapy with trastuzumab and paclitaxel was
      started. After the 6 courses of pharmacotherapy were completed, she was judged to
      have clinical CR, and subsequently underwent total breast excision(Bt)and skin
      grafting. No visible cancer cell was observed in the resected specimens,
      pathological CR was diagnosed. Postoperatively, the patient is receiving
      trastuzumab alone every other week, and at present 10 months after the second
      operation, the patient is in CR status and is visiting the outpatient clinic. No
      severe side effects (over grade 3) from this therapy have been observed. It is
      suggested that combination therapy with trastuzumab and paclitaxel for
      inflammatory local recurrence after breast conserving surgery is a treatment of
      choice.

PMID- 16110295
TI  - Huge cavernous hemangioma arising in a male breast.
AB  - We report a rare case of a huge cavernous hemangioma arising in a male breast. A
      60-year-old man first noticed 1 x 2 cm elastic hard nodule just below his right
      nipple ten years previously. It enlarged 5 x 5 cm over six years. When he came to
      our clinic, it was size of child head (510 mm in circumference),was an elastic
      hard with a rather smooth surface, and firmly fixed to the chest wall. Magnetic
      resonance imaging (MRI) and multidetectocomputed tomography (MDCT)showed a large
      mass infiltrating into the chest wall. Fine needle aspiration cytology (FNA) and
      core needle biopsy (CNB) failed to obtain proper material except for old bloody
      fluid or necrotic connective tissue, precluding a correct diagnosis
      preoperatively. Mastectomy with partial resection of the chest wall was
      subsequently performed. Histologically, it was found to be a cavernous hemangioma
      without cellular atypia. In such a case, complete excision is recommended to
      exclude the possibility of an underlying malignant lesion.

PMID- 16110296
TI  - A Case of Burkitt's Lymphoma Involving Both Breasts.
AB  - Primary malignant lymphoma of the breast is rare, and Burkitt's lymphoma is
      especially rare. We report the case of a 44-year-old woman in whom Burkitt's
      lymphoma involving both breasts was diagnosed. The patient was referred to our
      hospital because of a diffuse, firm swelling, like a bulky ball, in both breasts.
      Fine-needle aspiration cytology (FNAC) of both breast masses revealed malignant
      lymphoma(ML), and diffuse large B-cell lymphoma was diagnosed based on the
      results of immunohistochemical studies of a core needle biopsy specimen. The
      gallium scan revealed very hot lesions in both breasts, but there was no evidence
      of disseminated disease. We instituted initial therapy, with cyclophosphamide,
      doxorubicin, vincristine, and prednisone (CHOP) plus intrathecal chemotherapy
      without performing a chromosome analysis, because the clinical course was very
      aggressive. A CR was achieved, but after eight cycles of CHOP therapy, the ML
      relapsed. We then resected the mass in the left breast, and when examination of
      the surgical specimen revealed relapse of ML and t (8;11) (q24;q32)
      translocation, Burkitt's lymphoma was diagnosed. High-dose chemotherapy followed
      by peripheral-blood stem cell transplantation was performed, but the patient died
      10 months after her initial presentation at our hospital.

PMID- 16110297
TI  - A case of unilateral gravid macromastia in 23-year-old Japanese woman associated
      with elevated serum CA19-9.
AB  - We report a rare case of gravid macromastia (GM) treated after delivery. A 23
      year-old woman with left breast enlargement was referred to our hospital.
      Laboratory investigations revealed an elevated serum CA19-9 level of 200.3 U/ml.
      Gravid macromastia was diagnosed by clinical examination (US, MRI) and 11G
      mammotome biopsy. Tumorectomy of the left breast and mammoplasty were performed.
      The mass had proliferated to the exclusion of normal gland. Histological
      examination revealed abundant proliferation of stromal loose connective tissue
      and interposed fat cells surrounding normal and lactating lobules. The epithelial
      cells were positive for CA19-9 on immunohistochemical staining. Serum CA19-9
      decreased to normal levels 3 months after operation. GM is exceedingly rare and
      occurs in less than 0.001-0.003% of all pregnant women. Once established, the
      condition is likely to continue to successive pregnancies. This benign tumor is
      sometimes difficult to distinguish from malignant tumors since it shows few
      histological characteristics and grows rapidly. Attention is necessary to
      diagnose tumors of the breast during pregnancy.

PMID- 16110298
TI  - Cryptogenic organizing pneumonia after radiotherapy for breast cancer.
AB  - We report a case of lasting fever and cough with pulmonary infiltrates
      progressing 4 months after adjuvant radiotherapy following surgery for breast
      cancer. Chest radiography and computed tomography demonstrated alveolar opacities
      outside the irradiated pulmonary area. Laboratory data revealed neutrophilia and
      increased levels of C-reactive protein. Bronchoalveolar lavage fluid displayed
      increased lymphocyte counts, and transbronchial lung biopsy revealed histological
      patterns compatible with cryptogenic organizing pneumonia (COP). Corticosteroid
      therapy resulted in marked clinical improvement. From the histological and
      clinical findings, this case was judged to be a case of COP induced after
      radiotherapy for breast cancer, similar to those reported recently.

PMID- 16110299
TI  - VAMP5 and VAMP8 are most likely not involved in primary open-angle glaucoma.
AB  - PURPOSE: To select and characterize novel POAG disease genes. On the basis of
      genetic position (GLC1B), expression in the optic nerve, and biochemical function
      (targeted membrane transport processes), we selected the human VAMP5 and VAMP8
      (encoding vesicle-associated membrane proteins 5 and 8) as potential candidate
      disease genes for POAG. We subsequently analyzed whether or not sequence changes
      in VAMP5 or VAMP8 were implicated in POAG. METHODS: Genomic DNA samples from 90
      POAG cases and 60 controls were screened by denaturing high performance liquid
      chromatography of fragments amplified by the polymerase chain reaction. Direct
      sequencing identified nucleotide changes. RESULTS: No nonsynonymous rare sequence
      variants were found in VAMP5 or VAMP8. In VAMP5, three previously identified and
      five new single nucleotide polymorphisms (SNPs) were found. In VAMP8, four known
      and two new SNPs were detected. All new SNPs did not appear to change gene
      function or alter gene splicing. No significant differences were found between
      the allele frequencies in POAG cases and controls. CONCLUSIONS: Our findings
      indicate that VAMP5 and VAMP8 are not involved in POAG in the Dutch population.

PMID- 16110300
TI  - CRYBB1 mutation associated with congenital cataract and microcornea.
AB  - PURPOSE: The molecular characterization of a UK family with an autosomal dominant
      congenital cataract associated with microcornea is reported. METHODS: Family
      history and clinical data were recorded. This phenotype was linked to a 7.6 cM
      region of chromosome 22q11.2-q12.2, spanning the beta-crystallin gene cluster
      (ZMax of 3.91 for marker D22S1114 at theta=0). Candidate genes were PCR amplified
      and screened for mutations on both strands using direct sequencing. RESULTS:
      Sequencing of the coding regions and flanking intronic sequences of CRYBB2 and
      CRYBB1 showed the presence of a novel, heterozygous X253R change in exon 6 of
      CRYBB1. SSCP analysis confirmed that this sequence change segregated with the
      disease phenotype in all available family members and was not found in 109
      ethnically matched controls. CONCLUSIONS: X253R is predicted to elongate the COOH
      terminal extension of the protein and would be expected to disrupt beta
      crystallin interactions. This is the first documented involvement of CRYBB1 in
      ocular development beyond cataractogenesis.

PMID- 16110301
TI  - Concentration and distribution of ubiquinone (coenzyme Q), the endogenous lipid
      antioxidant, in the rat lens: effect of treatment with simvastatin.
AB  - PURPOSE: Ubiquinone (Ub) is the only known endogenously synthesized lipid soluble
      antioxidant. It is synthesized from intermediates in the cholesterol metabolic
      pathway. Our goal was to identify the Ubs and determine the concentration and
      distribution of Ubs in the rat lens and the effect of treatment with simvastatin,
      a cholesterol synthesis inhibitor, on lens levels. METHODS: Intact lenses and
      separated lens fractions from young rats were homogenized in organic solvents,
      the Ubs recovered, and identified by HPLC analysis. Rats were fed Ub-10 to
      determine effects of supplementation on tissue levels. Sprague-Dawley (SD) and
      Chbb:Thom (CT) rats were treated with simvastatin, an inducer of cataracts in CT
      rats, to determine its effects on lens Ubs. RESULTS: Ubiquinone-9 (9 isoprenes in
      its hydrocarbon tail) was the main Ub in the rat lens. The intact lens contained
      about 3.0 microg Ub/g lens wet weight of which 80-90% was Ub-9 and the remainder
      Ub-10. No reduced Ubs were detected. Although the epithelial fraction contained
      the highest Ub concentration (about 8 microg/g), the cortex and nucleus combined
      accounted for about 90% of the lens' total content. Dietary supplementation with
      Ub-10 markedly increased the Ub-10 concentration in liver but not lens. Treatment
      with simvastatin decreased lens Ubs of both SD and CT rats by about 20%.
      CONCLUSIONS: The abundance of mitochondria in lens epithelium likely accounted
      for its high level of Ubs; but, finding most of the lens' total Ub in the cortex
      plus nucleus also suggests roles in maintaining the fiber cell membrane. The
      decrease in lens Ubs caused by simvastatin is interpreted to reflect a response
      to drug induced cellular stress rather than to inhibition of the cholesterol
      synthesis pathway.

PMID- 16110302
TI  - The apolipoprotein E gene polymorphism is associated with open angle glaucoma in
      the Japanese population.
AB  - PURPOSE: To assess whether genetic polymorphisms of the apolipoprotein E (APOE)
      gene are associated with open angle glaucoma (OAG) in the Japanese population.
      METHODS: Genomic DNA was examined in a cohort of 310 Japanese patients with OAG
      and 179 control subjects. The average age was 63.5+/-14.4 years (mean+/-SD) for
      the OAG patients and 65.5+/-11.6 years for the control subjects. The presence or
      absence of OAG in patients and controls was based on clinical examination and/or
      ophthalmic records. The APOE allele frequency (epsilon2, epsilon3, and epsilon4
      alleles) was studied by restriction fragment length polymorphism, and compared
      between OAG patients and control subjects. The association between the
      intraocular pressure (IOP) and the APOE alleles was also evaluated. RESULTS:
      There was a significant difference in the APOE genotype frequencies between these
      groups (p=0.0006 chi2 test). The frequencies of the epsilon2 and epsilon4 alleles
      were significantly lower in the OAG patients (epsilon2: 2.6%; epsilon4: 6.0%)
      compared to the control subjects (epsilon2: 5.0%, p=0.048; epsilon4: 10.6%,
      p=0.012; Fisher's exact test). The frequency of the epsilon3 allele was
      significantly higher in the OAG patients (91.4%) compared to the control subjects
      (84.4%, p=0.0010; Fisher's exact test). Adjusted for age, gender, and IOP, an
      appropriate three fold reduction in OAG risk (odds ratio [OR] 0.29, 95%
      confidence interval [CI] 0.10 to 0.80; p=0.018) was found with the epsilon2
      allele and a two fold increased risk of OAG (OR 1.97, 95% CI 1.06 to 3.67;
      p=0.033) was found with the epsilon3 allele. The maximum IOP (18.3+/-6.0 mm Hg)
      in patients with the epsilon4 allele was significantly lower than that (21.3+/
      9.1 mm Hg) in patients without the epsilon4 allele (p=0.006, Student's t-test).
      CONCLUSIONS: The APOE gene polymorphism is associated with OAG in the Japanese
      population. Further studies in the other ethnic populations should be performed
      to elucidate the relationship between APOE and OAG.

PMID- 16110303
TI  - Versican splice variants in human trabecular meshwork and ciliary muscle.
AB  - PURPOSE: Versican, chondroitin sulfate glycoprotein 2, is thought to play a role
      in regulating aqueous humor outflow and intraocular pressure via the human
      trabecular meshwork (HTM) of the eye. This protein was upregulated in HTM cells
      when they were treated with TGF-beta. There are four splice variant forms of
      versican (V0-V3) with different numbers of glycoaminoglycan (GAG) attachment
      domains. In this study, we investigated the various isoforms of versican from
      ocular tissues and cultured cells. METHODS: HTM and human ciliary muscle (HCM)
      tissues were dissected from three pairs of donors eyes with no histories of eye
      disease. Cultures of HTM and HCM cells were established from five donor eyes, and
      HTM cells were treated for 72 h with 1 ng/ml of either with hrTGF-beta1 or hrTGF
      beta2. Total RNA was isolated from cells and tissues from each of the samples.
      Relative quantitation of gene expression of each variant was detected by real
      time PCR with SYBR Green dye. RESULTS: All four variants of versican existed in
      each sample. In cultured HTM cells, the two variants with the largest number of
      GAG domains predominate. The V1 form is about 20% greater than the V0 form. There
      is an upregulation, particularly in the V0 form, when the cells are cultured. In
      tissue, the V1 form is about five fold greater than the other three. In the
      ocular ciliary muscle, the V1 form is the most prominent, but with this tissue,
      the relative amount of the V0 form did not change when cells were cultured. There
      was an upregulation of all splice variants in HTM cells when they were cultured
      with either TGF-beta1 or TGF-beta2. The increase in expression in the HTM with
      TGF-beta treatments were greatest with the V0 and V2 forms. CONCLUSIONS: This is
      the first report about the presence of various forms of versican in the anterior
      segment of the eye and the alterations in the mRNA patterns of these forms when
      cells are placed in culture. The results indicate the variants with the largest
      numbers of GAG attachment domains are the most prominent in the HTM and HCM. The
      increases in these forms that have the most GAG domains would be consistent with
      the increases in chondroitin sulfate reported in glaucoma.

PMID- 16110311
TI  - Growth inhibition efficacy of an adenovirus expressing dual therapeutic genes,
      wild-type p53, and anti-erbB2 ribozyme, against human bladder cancer cells.
AB  - The altered expression of both p53 and erbB2 is strongly related to the disease
      status and the outcome of bladder cancers. We examined the antitumor efficacy by
      the modulation of these genetic alterations with a newly designed dual-gene
      expressing adenovirus (Ad-p53/erbB2Rz), which expresses p53 and anti-erbB2
      ribozyme simultaneously in human bladder cancer cells. Cell growth inhibition
      efficacy along with biological responses of this virus was compared with other
      viral vectors (Ad-p53, which expresses wild-type p53 cDNA, and Ad-erbB2Rz, which
      expresses anti-erbB2 ribozyme, solely or in combination). Sufficient transgene
      expression in targeted cells and the altered expression of the targeted genes and
      their encoded proteins were obtained by each therapeutic vector. Each of the
      three therapeutic viral vectors inhibited bladder cancer cell growth, and the
      putative additive antitumor effect was shown by the combination of two of the
      therapeutic vectors. Furthermore, Ad-p53/erbB2Rz had superior therapeutic
      efficacy when the same titers of viruses were infected. Nonspecific vector
      related toxicity was minimized by reducing the total amount of viral titers by
      using the dual-gene-expressing adenovirus. Modulation of multiple genetic
      abnormalities might enhance the therapeutic efficacy, and vector-related toxicity
      could be minimized when the total amount of viral titers are reduced.

PMID- 16110312
TI  - Retrovirus-mediated tk gene therapy of implanted human breast cancer in nude mice
      under the regulation of Tet-On.
AB  - Tight regulation of the therapeutic gene expression is critical in gene therapy.
      In this report, a doxycycline (Dox)-regulated retrovirus-mediated gene expression
      system was used to study the effects of suicide gene therapy on human breast
      cancer cell line MCF-7 and the nude mice model of implanted human breast cancer.
      To render the expression of suicide gene under control, we used two pseudoviruses
      simultaneously, RevTRE/HSVtk and RevTet-On, to infect MCF-7 cells or xenografts
      of nude mice. When infected by the pseudoviruses and followed by Dox and
      Ganciclovir (GCV) treatment, MCF-7 cells were arrested at S phase and the growth
      was suppressed. We then evaluated the antitumor efficiency of this system in vivo
      through studying the mice bearing human breast cancer xenografts. Compared with
      control groups, the HSVtk mRNA level increased significantly in tumor tissues,
      mass of the tumors shrank remarkably, and tumor necrosis features occurred after
      treatment with Dox and GCV. These data suggest that suicide gene therapy using
      the Dox-induced Tet-On-controlled HSVtk gene expression system is a feasible
      method to treat human breast cancer.

PMID- 16110313
TI  - Targeted gene therapy for breast cancer with truncated Bid.
AB  - We studied the efficiency of the proapoptotic factor tBid, targeted to tumor
      cells using the promoters of the hTERT, Survivin and Muc1 genes, in killing
      breast cancer cells. tBid is the active fragment of the proapoptotic protein Bid
      and is generated in response to death receptor activation. When placed under
      control of a strong CMV promoter, tBid was highly efficient in killing breast
      cancer cells. When expression of tBid was driven by tumor-specific promoters, the
      magnitude of killing was significant in cell lines with high levels of promoter
      activity. For successful gene therapy with targeted tBid, it is therefore crucial
      to be able to predict promoter activity prior to selection of the therapeutic
      construct. To test whether gene expression could serve as a predictor, we
      correlated expression of Survivin, hTERT and Muc1 genes with the activity of the
      corresponding promoters in a panel of breast cancer cell lines. Expression of the
      Muc1 gene correlated well with the activity of its promoter and the resultant
      tumor cell killing. For the hTERT and Survivin promoters, however, promoter
      activity did not correlate well with the expression of the corresponding genes.
      The implications and possible mechanism of these discrepancies are discussed.

PMID- 16110314
TI  - The influence of the Internet on immunology education.
AB  - The potential of the Internet as a medium through which to teach basic and
      applied immunology lies in the ability to illustrate complex concepts in new ways
      for audiences that are diverse and often geographically dispersed. This article
      explores two collaborative Internet-based learning projects (also known as e
      learning projects) that are under development: Immunology Online, which will
      present an Internet-based curriculum in basic and clinical immunology to Swiss
      undergraduate and graduate students across five campuses; and the OCTAVE project,
      which will offer online training to an international cadre of new investigators,
      the members of which are carrying out clinical trials of vaccines against HIV
      infection.

PMID- 16110315
TI  - Regulation of immune cells by local-tissue oxygen tension: HIF1 alpha and
      adenosine receptors.
AB  - Immune cells are often exposed to low oxygen tensions, which markedly affect
      cellular metabolism. We describe how activated T cells adapt to the changing
      energy supplies in hypoxic areas of inflamed tissues by using hypoxia-inducible
      factor 1 (HIF1) to switch to glycolysis as the main source of energy and by
      signalling through extracellular-adenosine receptors. This hypoxic regulation
      might alter the balance between T helper 1 cells and T helper 2 cells and might
      alter the activities of cells of the innate immune system, thereby qualitatively
      and quantitatively affecting immune responses. This regulatory mechanism should
      be taken into account in the design and interpretation of in vitro and in vivo
      studies of immune-cell effector functions.

PMID- 16110316
TI  - The yin and yang of type I interferon activity in bacterial infection.
AB  - Interferons (IFNs) are cytokines that are important for immune responses,
      particularly to intracellular pathogens. They are divided into two structurally
      and functionally distinct types that interact with different cell-surface
      receptors. Classically, type I IFNs are potent antiviral immunoregulators,
      whereas the type II IFN enhances antibacterial immunity. However, as outlined
      here, type I IFNs are also produced in response to infection with other
      pathogens, and an increasing body of work shows that type I IFNs have an
      important role in the host response to bacterial infection. Strikingly, their
      activity can be either favourable or detrimental, and can influence various
      immune effector mechanisms.

PMID- 16110317
TI  - Urothelial tumorigenesis: a tale of divergent pathways.
AB  - Urothelial carcinoma of the bladder is unique among epithelial carcinomas in its
      divergent pathways of tumorigenesis. Low-grade papillary tumours rarely become
      muscle-invasive and they frequently harbour gene mutations that constitutively
      activate the receptor tyrosine kinase-Ras pathway. By contrast, most high-grade
      invasive tumours progress to life-threatening metastases and have defects in the
      p53 and the retinoblastoma protein pathways. Correcting pathway-specific defects
      represents an attractive strategy for the molecular therapy of urothelial
      carcinomas.

PMID- 16110318
TI  - Wilms' tumour: connecting tumorigenesis and organ development in the kidney.
AB  - Wilms' tumour, or nephroblastoma, is a common childhood tumour that is intimately
      linked to early kidney development and is often associated with persistent
      embryonic renal tissue and other kidney abnormalities. WT1, the first gene found
      to be inactivated in Wilms' tumour, encodes a transcription factor that functions
      as both a tumour suppressor and a critical regulator of renal organogenesis. Our
      understanding of the roles of WT1 in tumour formation and organogenesis have
      advanced in parallel, providing a striking example of the intersection between
      tumour biology, cellular differentiation and normal organogenesis.

PMID- 16110319
TI  - The concept of synthetic lethality in the context of anticancer therapy.
AB  - Two genes are synthetic lethal if mutation of either alone is compatible with
      viability but mutation of both leads to death. So, targeting a gene that is
      synthetic lethal to a cancer-relevant mutation should kill only cancer cells and
      spare normal cells. Synthetic lethality therefore provides a conceptual framework
      for the development of cancer-specific cytotoxic agents. This paradigm has not
      been exploited in the past because there were no robust methods for
      systematically identifying synthetic lethal genes. This is changing as a result
      of the increased availability of chemical and genetic tools for perturbing gene
      function in somatic cells.

PMID- 16110320
TI  - Apaf-1 expression in malignant melanoma.

PMID- 16110321
TI  - Unilineage monocytopoiesis in hematopoietic progenitor culture: switching
      cytokine treatment at all Mo developmental stages induces differentiation into
      dendritic cells.
AB  - We have developed a new culture system whereby human hematopoietic progenitors
      purified from adult peripheral blood extensively proliferate and gradually
      differentiate into >95% pure monocytic (Mo) cells. At all developmental stages
      treatment with interleukin (IL)-4+granulocyte-macrophage colony-stimulating
      factor or IL-4+c-Kit-ligand+FLT-3 ligand switched the Mo precursors into
      dendritic cells (DCs). The switching capacity decreased only at the end of the
      culture, when most Mo cells matured to macrophages. Moreover, the Mo precursors
      were highly susceptible to transduction with lentiviral vectors: once switched to
      DCs, they maintained the transgene expression, as well as the phenotype and
      function of the DC lineage. Our results provide new insight into the potential
      role of the Mo lineage as a reservoir of DCs in vivo. Furthermore, the
      methodology for transduction of Mo precursors provides a tool to generate
      genetically modified, normally functioning DCs potentially useful for
      immunotherapy.

PMID- 16110322
TI  - Deregulated expression of DeltaNp73alpha causes early embryonic lethality.

PMID- 16110323
TI  - Tonsillar homing of Epstein-Barr virus-specific CD8+ T cells and the virus-host
      balance.
AB  - Patients with infectious mononucleosis (IM) undergoing primary EBV infection show
      large expansions of EBV-specific CD8+ T cells in the blood. While latent
      infection of the B cell pool is quickly controlled, virus shedding from lytically
      infected cells in the oropharynx remains high for several months. We therefore
      studied how responses localize to the tonsil, a major target site for EBV, during
      primary infection and persistence. In acute IM, EBV-specific effectors were
      poorly represented among CD8+ T cells in tonsil compared with blood, coincident
      with absence of the CCR7 lymphoid homing marker on these highly activated cells.
      In patients who had recently recovered from IM, latent epitope reactivities were
      quicker than lytic reactivities both to acquire CCR7 and to accumulate in the
      tonsil, with some of these cells now expressing the CD103 integrin, which
      mediates retention at mucosal sites. By contrast, in long-term virus carriers in
      whom both lytic and latent infections had been controlled, there was 2- to 5-fold
      enrichment of lytic epitope reactivities and 10- to 20-fold enrichment of latent
      epitope reactivities in tonsil compared with blood; up to 20% of tonsillar CD8+ T
      cells were EBV specific, and many now expressed CD103. We suggest that efficient
      control of EBV infection requires appropriate CD8+ T cell homing to oropharyngeal
      sites.

PMID- 16110324
TI  - TWEAK induces liver progenitor cell proliferation.
AB  - Progenitor ("oval") cell expansion accompanies many forms of liver injury,
      including alcohol toxicity and submassive parenchymal necrosis as well as
      experimental injury models featuring blocked hepatocyte replication. Oval cells
      can potentially become either hepatocytes or biliary epithelial cells and may be
      critical to liver regeneration, particularly when hepatocyte replication is
      impaired. The regulation of oval cell proliferation is incompletely understood.
      Herein we present evidence that a TNF family member called TWEAK (TNF-like weak
      inducer of apoptosis) stimulates oval cell proliferation in mouse liver through
      its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to
      be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes
      exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in
      adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing
      adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4
      dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in
      adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK
      stimulated the proliferation of an oval cell culture model. Finally, we show
      increased Fn14 expression in chronic hepatitis C and other human liver diseases
      relative to its expression in normal liver, which suggests a role for the
      TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective
      mitogenic effect for liver oval cells that distinguishes it from other previously
      described growth factors.

PMID- 16110325
TI  - Magnetic resonance spectroscopy reveals that activated monocytes contribute to
      neuronal injury in SIV neuroAIDS.
AB  - Difficulties in understanding the mechanisms of HIV neuropathogenesis include the
      inability to study dynamic processes of infection, cumulative effects of the
      virus, and contributing host immune responses. We used H magnetic resonance
      spectroscopy and studied monocyte activation and progression of CNS neuronal
      injury in a CD8 lymphocyte depletion model of neuroAIDS in SIV-infected rhesus
      macaque monkeys. We found early, consistent neuronal injury coincident with
      viremia and SIV infection/activation of monocyte subsets and sought to define the
      role of plasma virus and monocytes in contributing to CNS disease. Antiretroviral
      therapy with essentially non-CNS-penetrating agents resulted in slightly
      decreased levels of plasma virus, a significant reduction in the number of
      activated and infected monocytes, and rapid, near-complete reversal of neuronal
      injury. Robust macrophage accumulation and productive virus replication were
      found in brains of infected and CD8 lymphocyte-depleted animals, but no
      detectable virus and few scattered infiltrating macrophages were observed in CD8
      lymphocyte-depleted animals compared with animals not receiving antiretroviruses
      that were sacrificed at the same time after infection. These results underscore
      the role of activated monocytes and monocyte infection outside of the brain in
      driving CNS disease.

PMID- 16110326
TI  - Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium
      bovis bacille Calmette-Guerin mutants that secrete listeriolysin.
AB  - The tuberculosis vaccine Mycobacterium bovis bacille Calmette-Guerin (BCG) was
      equipped with the membrane-perforating listeriolysin (Hly) of Listeria
      monocytogenes, which was shown to improve protection against Mycobacterium
      tuberculosis. Following aerosol challenge, the Hly-secreting recombinant BCG
      (hly+ rBCG) vaccine was shown to protect significantly better against aerosol
      infection with M. tuberculosis than did the parental BCG strain. The isogenic,
      urease C-deficient hly+ rBCG (DeltaureC hly+ rBCG) vaccine, providing an
      intraphagosomal pH closer to the acidic pH optimum for Hly activity, exhibited
      still higher vaccine efficacy than parental BCG. DeltaureC hly+ rBCG also induced
      profound protection against a member of the M. tuberculosis Beijing/W genotype
      family while parental BCG failed to do so consistently. Hly not only promoted
      antigen translocation into the cytoplasm but also apoptosis of infected
      macrophages. We concluded that superior vaccine efficacy of DeltaureC hly+ rBCG
      as compared with parental BCG is primarily based on improved cross-priming, which
      causes enhanced T cell-mediated immunity.

PMID- 16110328
TI  - TRPA1 induced in sensory neurons contributes to cold hyperalgesia after
      inflammation and nerve injury.
AB  - Cold hyperalgesia is a well-documented symptom of inflammatory and neuropathic
      pain; however, the underlying mechanisms of this enhanced sensitivity to cold are
      poorly understood. A subset of transient receptor potential (TRP) channels
      mediates thermosensation and is expressed in sensory tissues, such as nociceptors
      and skin. Here we report that the pharmacological blockade of TRPA1 in primary
      sensory neurons reversed cold hyperalgesia caused by inflammation and nerve
      injury. Inflammation and nerve injury increased TRPA1, but not TRPM8, expression
      in tyrosine kinase A-expressing dorsal root ganglion (DRG) neurons. Intrathecal
      administration of anti-nerve growth factor (anti-NGF), p38 MAPK inhibitor, or
      TRPA1 antisense oligodeoxynucleotide decreased the induction of TRPA1 and
      suppressed inflammation- and nerve injury-induced cold hyperalgesia. Conversely,
      intrathecal injection of NGF, but not glial cell line-derived neurotrophic
      factor, increased TRPA1 in DRG neurons through the p38 MAPK pathway. Together,
      these results demonstrate that an NGF-induced TRPA1 increase in sensory neurons
      via p38 activation is necessary for cold hyperalgesia. Thus, blocking TRPA1 in
      sensory neurons might provide a fruitful strategy for treating cold hyperalgesia
      caused by inflammation and nerve damage.

PMID- 16110329
TI  - Noninvasive imaging of pancreatic inflammation and its reversal in type 1
      diabetes.
AB  - A major stumbling block for research on and treatment of type 1 diabetes is the
      inability to directly, but noninvasively, visualize the lymphocytic/inflammatory
      lesions in the pancreatic islets. One potential approach to surmounting this
      impediment is to exploit MRI of magnetic nanoparticles (MNP) to visualize changes
      in the microvasculature that invariably accompany inflammation. MNP-MRI did
      indeed detect vascular leakage in association with insulitis in murine models of
      type 1 diabetes, permitting noninvasive visualization of the inflammatory lesions
      in vivo in real time. We demonstrate, in proof-of-principle experiments, that
      this strategy allows one to predict, within 3 days of completing treatment with
      an anti-CD3 monoclonal antibody, which NOD mice with recent-onset diabetes are
      responding to therapy and may eventually be cured. Importantly, an essentially
      identical MNP-MRI strategy has previously been used with great success to image
      lymph node metastases in prostate cancer patients. This success strongly argues
      for rapid translation of these preclinical observations to prediction and/or
      stratification of type 1 diabetes and treatment of individuals with the disease;
      this would provide a crucially needed early predictor of response to therapy.

PMID- 16110327
TI  - ATP and purinergic receptor-dependent membrane traffic in bladder umbrella cells.
AB  - The umbrella cells that line the bladder are mechanosensitive, and bladder
      filling increases the apical surface area of these cells; however, the upstream
      signals that regulate this process are unknown. Increased pressure stimulated ATP
      release from the isolated uroepithelium of rabbit bladders, which was blocked by
      inhibitors of vesicular transport, connexin hemichannels, ABC protein family
      members, and nucleoside transporters. Pressure-induced increases in membrane
      capacitance (a measure of apical plasma membrane surface area where 1 microF
      approximately equals 1 cm2) were inhibited by the serosal, but not mucosal,
      addition of apyrase or the purinergic receptor antagonist PPADS. Upon addition of
      purinergic receptor agonists, increased capacitance was observed even in the
      absence of pressure. Moreover, knockout mice lacking expression of P2X2 and/or
      P2X3 receptors failed to show increases in apical surface area when exposed to
      hydrostatic pressure. Treatments that prevented release of Ca2+ from
      intracellular stores or activation of PKA blocked ATPgammaS-stimulated changes in
      capacitance. These results indicate that increased hydrostatic pressure
      stimulates release of ATP from the uroepithelium and that upon binding to P2X and
      possibly P2Y receptors on the umbrella cell, downstream Ca2+ and PKA second
      messenger cascades may act to stimulate membrane insertion at the apical pole of
      these cells.

PMID- 16110330
TI  - Recognition of unknown conserved alternatively spliced exons.
AB  - The split structure of most mammalian protein-coding genes allows for the
      potential to produce multiple different mRNA and protein isoforms from a single
      gene locus through the process of alternative splicing (AS). We propose a
      computational approach called UNCOVER based on a pair hidden Markov model to
      discover conserved coding exonic sequences subject to AS that have so far gone
      undetected. Applying UNCOVER to orthologous introns of known human and mouse
      genes predicts skipped exons or retained introns present in both species, while
      discriminating them from conserved noncoding sequences. The accuracy of the model
      is evaluated on a curated set of genes with known conserved AS events. The
      prediction of skipped exons in the approximately 1% of the human genome
      represented by the ENCODE regions leads to more than 50 new exon candidates. Five
      novel predicted AS exons were validated by RT-PCR and sequencing analysis of 15
      introns with strong UNCOVER predictions and lacking EST evidence. These results
      imply that a considerable number of conserved exonic sequences and associated
      isoforms are still completely missing from the current annotation of known genes.
      UNCOVER also identifies a small number of candidates for conserved intron
      retention.

PMID- 16110331
TI  - Theoretical analysis of pre-receptor image conditioning in weakly electric fish.
AB  - Electroreceptive fish detect nearby objects by processing the information
      contained in the pattern of electric currents through the skin. The distribution
      of local transepidermal voltage or current density on the sensory surface of the
      fish's skin is the electric image of the surrounding environment. This article
      reports a model study of the quantitative effect of the conductance of the
      internal tissues and the skin on electric image generation in Gnathonemus
      petersii (Gunther 1862). Using realistic modelling, we calculated the electric
      image of a metal object on a simulated fish having different combinations of
      internal tissues and skin conductances. An object perturbs an electric field as
      if it were a distribution of electric sources. The equivalent distribution of
      electric sources is referred to as an object's imprimence. The high conductivity
      of the fish body lowers the load resistance of a given object's imprimence,
      increasing the electric image. It also funnels the current generated by the
      electric organ in such a way that the field and the imprimence of objects in the
      vicinity of the rostral electric fovea are enhanced. Regarding skin conductance,
      our results show that the actual value is in the optimal range for transcutaneous
      voltage modulation by nearby objects. This result suggests that "voltage" is the
      answer to the long-standing question as to whether current or voltage is the
      effective stimulus for electroreceptors. Our analysis shows that the fish body
      should be conceived as an object that interacts with nearby objects, conditioning
      the electric image. The concept of imprimence can be extended to other sensory
      systems, facilitating the identification of features common to different
      perceptual systems.

PMID- 16110332
TI  - Computational ecology: from the complex to the simple and back.

PMID- 16110333
TI  - Inflammatory aetiology of human myometrial activation tested using directed
      graphs.
AB  - There are three main hypotheses for the activation of the human uterus at labour:
      functional progesterone withdrawal, inflammatory stimulation, and oxytocin
      receptor activation. To test these alternatives we have taken information and
      data from the literature to develop causal pathway models for the activation of
      human myometrium. The data provided quantitative RT-PCR results on key genes from
      samples taken before and during labour. Principal component analysis showed that
      pre-labour samples form a homogenous group compared to those during labour. We
      therefore modelled the alternative causal pathways in non-laboring samples using
      directed graphs and statistically compared the likelihood of the different models
      using structural equations and D-separation approaches. Using the computer
      program LISREL, inflammatory activation as a primary event was highly consistent
      with the data (p = 0.925), progesterone withdrawal, as a primary event, is
      plausible (p = 0.499), yet comparatively unlikely, oxytocin receptor mediated
      initiation is less compatible with the data (p = 0.091). DGraph, a software
      program that creates directed graphs, produced similar results (p= 0.684, p=
      0.280, and p = 0.04, respectively). This outcome supports an inflammatory
      aetiology for human labour. Our results demonstrate the value of directed graphs
      in determining the likelihood of causal relationships in biology in situations
      where experiments are not possible.

PMID- 16110334
TI  - Molecular switches at the synapse emerge from receptor and kinase traffic.
AB  - Changes in the synaptic connection strengths between neurons are believed to play
      a role in memory formation. An important mechanism for changing synaptic strength
      is through movement of neurotransmitter receptors and regulatory proteins to and
      from the synapse. Several activity-triggered biochemical events control these
      movements. Here we use computer models to explore how these putative memory
      related changes can be stabilised long after the initial trigger, and beyond the
      lifetime of synaptic molecules. We base our models on published biochemical data
      and experiments on the activity-dependent movement of a glutamate receptor,
      AMPAR, and a calcium-dependent kinase, CaMKII. We find that both of these
      molecules participate in distinct bistable switches. These simulated switches are
      effective for long periods despite molecular turnover and biochemical
      fluctuations arising from the small numbers of molecules in the synapse. The
      AMPAR switch arises from a novel self-recruitment process where the presence of
      sufficient receptors biases the receptor movement cycle to insert still more
      receptors into the synapse. The CaMKII switch arises from autophosphorylation of
      the kinase. The switches may function in a tightly coupled manner, or relatively
      independently. The latter case leads to multiple stable states of the synapse. We
      propose that similar self-recruitment cycles may be important for maintaining
      levels of many molecules that undergo regulated movement, and that these may lead
      to combinatorial possible stable states of systems like the synapse.

PMID- 16110335
TI  - The RNA silencing pathway: the bits and pieces that matter.
AB  - Cellular pathways are generally proposed on the basis of available experimental
      knowledge. The proposed pathways, however, may be inadequate to describe the
      phenomena they are supposed to explain. For instance, by means of concise
      mathematical models we are able to reveal shortcomings in the current description
      of the pathway of RNA silencing. The silencing pathway operates by cleaving
      siRNAs from dsRNA. siRNAs can associate with RISC, leading to the degradation of
      the target mRNA. We propose and analyze a few small extensions to the pathway: a
      siRNA degrading RNase, primed amplification of aberrant RNA pieces, and
      cooperation between aberrant RNA to trigger amplification. These extensions allow
      for a consistent explanation for various types of silencing phenomena, such as
      virus induced silencing, transgene and transposon induced silencing, and
      avoidance of self-reactivity, as well as for differences found between species
      groups.

PMID- 16110336
TI  - Combined evidence annotation of transposable elements in genome sequences.
AB  - Transposable elements (TEs) are mobile, repetitive sequences that make up
      significant fractions of metazoan genomes. Despite their near ubiquity and
      importance in genome and chromosome biology, most efforts to annotate TEs in
      genome sequences rely on the results of a single computational program,
      RepeatMasker. In contrast, recent advances in gene annotation indicate that high
      quality gene models can be produced from combining multiple independent sources
      of computational evidence. To elevate the quality of TE annotations to a level
      comparable to that of gene models, we have developed a combined evidence-model TE
      annotation pipeline, analogous to systems used for gene annotation, by
      integrating results from multiple homology-based and de novo TE identification
      methods. As proof of principle, we have annotated "TE models" in Drosophila
      melanogaster Release 4 genomic sequences using the combined computational
      evidence derived from RepeatMasker, BLASTER, TBLASTX, all-by-all BLASTN, RECON,
      TE-HMM and the previous Release 3.1 annotation. Our system is designed for use
      with the Apollo genome annotation tool, allowing automatic results to be curated
      manually to produce reliable annotations. The euchromatic TE fraction of D.
      melanogaster is now estimated at 5.3% (cf. 3.86% in Release 3.1), and we found a
      substantially higher number of TEs (n = 6,013) than previously identified (n =
      1,572). Most of the new TEs derive from small fragments of a few hundred
      nucleotides long and highly abundant families not previously annotated (e.g., INE
      1). We also estimated that 518 TE copies (8.6%) are inserted into at least one
      other TE, forming a nest of elements. The pipeline allows rapid and thorough
      annotation of even the most complex TE models, including highly deleted and/or
      nested elements such as those often found in heterochromatic sequences. Our
      pipeline can be easily adapted to other genome sequences, such as those of the D.
      melanogaster heterochromatin or other species in the genus Drosophila.

PMID- 16110337
TI  - Bioinformatics for whole-genome shotgun sequencing of microbial communities.
AB  - The application of whole-genome shotgun sequencing to microbial communities
      represents a major development in metagenomics, the study of uncultured microbes
      via the tools of modern genomic analysis. In the past year, whole-genome shotgun
      sequencing projects of prokaryotic communities from an acid mine biofilm, the
      Sargasso Sea, Minnesota farm soil, three deep-sea whale falls, and deep-sea
      sediments have been reported, adding to previously published work on viral
      communities from marine and fecal samples. The interpretation of this new kind of
      data poses a wide variety of exciting and difficult bioinformatics problems. The
      aim of this review is to introduce the bioinformatics community to this emerging
      field by surveying existing techniques and promising new approaches for several
      of the most interesting of these computational problems.

PMID- 16110338
TI  - A hybrid photoreceptor expressing both rod and cone genes in a mouse model of
      enhanced S-cone syndrome.
AB  - Rod and cone photoreceptors subserve vision under dim and bright light
      conditions, respectively. The differences in their function are thought to stem
      from their different gene expression patterns, morphologies, and synaptic
      connectivities. In this study, we have examined the photoreceptor cells of the
      retinal degeneration 7(rd7) mutant mouse, a model for the human enhanced S-cone
      syndrome (ESCS). This mutant carries a spontaneous deletion in the mouse ortholog
      of NR2E3, an orphan nuclear receptor transcription factor mutated in ESCS.
      Employing microarray and in situ hybridization analysis we have found that the
      rd7 retina contains a modestly increased number of S-opsin-expressing cells that
      ultrastructurally appear to be normal cones. Strikingly, the majority of the
      photoreceptors in the rd7 retina represent a morphologically hybrid cell type
      that expresses both rod- and cone-specific genes. In addition, in situ
      hybridization screening of genes shown to be up-regulated in the rd7 mutant
      retina by microarray identified ten new cone-specific or cone-enriched genes with
      a wide range of biochemical functions, including two genes specifically involved
      in glucose/glycogen metabolism. We suggest that the abnormal electroretinograms,
      slow retinal degeneration, and retinal dysmorphology seen in humans with ESCS
      may, in part, be attributable to the aberrant function of a hybrid photoreceptor
      cell type similar to that identified in this study. The functional diversity of
      the novel cone-specific genes identified here indicates molecular differences
      between rods and cones extending far beyond those previously discovered.

PMID- 16110339
TI  - Gametophytic selection in Arabidopsis thaliana supports the selective model of
      intron length reduction.
AB  - Why do highly expressed genes have small introns? This is an important issue, not
      least because it provides a testing ground to compare selectionist and neutralist
      models of genome evolution. Some argue that small introns are selectively
      favoured to reduce the costs of transcription. Alternatively, large introns might
      permit complex regulation, not needed for highly expressed genes. This "genome
      design" hypothesis evokes a regionalized model of control of expression and hence
      can explain why intron size covaries with intergene distance, a feature also
      consistent with the hypothesis that highly expressed genes cluster in genomic
      regions with high deletion rates. As some genes are expressed in the haploid
      stage and hence subject to especially strong purifying selection, the evolution
      of genes in Arabidopsis provides a novel testing ground to discriminate between
      these possibilities. Importantly, controlling for expression level, genes that
      are expressed in pollen have shorter introns than genes that are expressed in the
      sporophyte. That genes flanking pollen-expressed genes have average-sized introns
      and intergene distances argues against regional mutational biases and genomic
      design. These observations thus support the view that selection for efficiency
      contributes to the reduction in intron length and provide the first report of a
      molecular signature of strong gametophytic selection.

PMID- 16110341
TI  - Oscillating evolution of a mammalian locus with overlapping reading frames: an
      XLalphas/ALEX relay.
AB  - XLalphas and ALEX are structurally unrelated mammalian proteins translated from
      alternative overlapping reading frames of a single transcript. Not only are they
      encoded by the same locus, but a specific XLalphas/ALEX interaction is essential
      for G-protein signaling in neuroendocrine cells. A disruption of this interaction
      leads to abnormal human phenotypes, including mental retardation and growth
      deficiency. The region of overlap between the two reading frames evolves at a
      remarkable speed: the divergence between human and mouse ALEX polypeptides makes
      them virtually unalignable. To trace the evolution of this puzzling locus, we
      sequenced it in apes, Old World monkeys, and a New World monkey. We show that the
      overlap between the two reading frames and the physical interaction between the
      two proteins force the locus to evolve in an unprecedented way. Namely, to
      maintain two overlapping protein-coding regions the locus is forced to have high
      GC content, which significantly elevates its intrinsic evolutionary rate.
      However, the two encoded proteins cannot afford to change too quickly relative to
      each other as this may impair their interaction and lead to severe physiological
      consequences. As a result XLalphas and ALEX evolve in an oscillating fashion
      constantly balancing the rates of amino acid replacements. This is the first
      example of a rapidly evolving locus encoding interacting proteins via overlapping
      reading frames, with a possible link to the origin of species-specific
      neurological differences.

PMID- 16110340
TI  - Glucocorticoid receptor-dependent gene regulatory networks.
AB  - While the molecular mechanisms of glucocorticoid regulation of transcription have
      been studied in detail, the global networks regulated by the glucocorticoid
      receptor (GR) remain unknown. To address this question, we performed an
      orthogonal analysis to identify direct targets of the GR. First, we analyzed the
      expression profile of mouse livers in the presence or absence of exogenous
      glucocorticoid, resulting in over 1,300 differentially expressed genes. We then
      executed genome-wide location analysis on chromatin from the same livers,
      identifying more than 300 promoters that are bound by the GR. Intersecting the
      two lists yielded 53 genes whose expression is functionally dependent upon the
      ligand-bound GR. Further network and sequence analysis of the functional targets
      enabled us to suggest interactions between the GR and other transcription factors
      at specific target genes. Together, our results further our understanding of the
      GR and its targets, and provide the basis for more targeted glucocorticoid
      therapies.

PMID- 16110342
TI  - Prediction of transcriptional terminators in Bacillus subtilis and related
      species.
AB  - In prokaryotes, genes belonging to the same operon are transcribed in a single
      mRNA molecule. Transcription starts as the RNA polymerase binds to the promoter
      and continues until it reaches a transcriptional terminator. Some terminators
      rely on the presence of the Rho protein, whereas others function independently of
      Rho. Such Rho-independent terminators consist of an inverted repeat followed by a
      stretch of thymine residues, allowing us to predict their presence directly from
      the DNA sequence. Unlike in Escherichia coli, the Rho protein is dispensable in
      Bacillus subtilis, suggesting a limited role for Rho-dependent termination in
      this organism and possibly in other Firmicutes. We analyzed 463 experimentally
      known terminating sequences in B. subtilis and found a decision rule to
      distinguish Rho-independent transcriptional terminators from non-terminating
      sequences. The decision rule allowed us to find the boundaries of operons in B.
      subtilis with a sensitivity and specificity of about 94%. Using the same decision
      rule, we found an average sensitivity of 94% for 57 bacteria belonging to the
      Firmicutes phylum, and a considerably lower sensitivity for other bacteria. Our
      analysis shows that Rho-independent termination is dominant for Firmicutes in
      general, and that the properties of the transcriptional terminators are
      conserved. Terminator prediction can be used to reliably predict the operon
      structure in these organisms, even in the absence of experimentally known
      operons. Genome-wide predictions of Rho-independent terminators for the 57
      Firmicutes are available in the Supporting Information section.

PMID- 16110343
TI  - Comparative genomics and disorder prediction identify biologically relevant SH3
      protein interactions.
AB  - Protein interaction networks are an important part of the post-genomic effort to
      integrate a part-list view of the cell into system-level understanding. Using a
      set of 11 yeast genomes we show that combining comparative genomics and secondary
      structure information greatly increases consensus-based prediction of SH3
      targets. Benchmarking of our method against positive and negative standards gave
      83% accuracy with 26% coverage. The concept of an optimal divergence time for
      effective comparative genomics studies was analyzed, demonstrating that genomes
      of species that diverged very recently from Saccharomyces cerevisiae(S. mikatae,
      S. bayanus, and S. paradoxus), or a long time ago (Neurospora crassa and
      Schizosaccharomyces pombe), contain less information for accurate prediction of
      SH3 targets than species within the optimal divergence time proposed. We also
      show here that intrinsically disordered SH3 domain targets are more probable
      sites of interaction than equivalent sites within ordered regions. Our findings
      highlight several novel S. cerevisiae SH3 protein interactions, the value of
      selection of optimal divergence times in comparative genomics studies, and the
      importance of intrinsic disorder for protein interactions. Based on our results
      we propose novel roles for the S. cerevisiae proteins Abp1p in endocytosis and
      Hse1p in endosome protein sorting.

PMID- 16110345
TI  - Neuropharmacological, neuroprotective and amyloid precursor processing properties
      of selective MAO-B inhibitor antiparkinsonian drug, rasagiline.
AB  - Rasagiline (N-propargyl-1R-aminoindan) is a novel, highly potent, irreversible
      monoamine oxidase (MAO)-B inhibitor designed for use as an antiparkinsonian drug.
      Unlike selegiline, rasagiline is not derived from amphetamine or metabolized to
      neurotoxic l-methamphetamine derivative, and it does not have sympathomimetic
      activity. Moreover, at selective MAO-B inhibitory dosage, it does not induce a
      "cheese reaction." Rasagiline is effective as monotherapy or as an adjunct to L
      dopa for patients with early and late Parkinson's disease. Adverse events do not
      occur with greater frequency in subjects receiving rasagiline than in those on
      placebo. Its S-isomer, TVP1022, is more than a thousand times less potent as an
      MAO inhibitor. However, both drugs have neuroprotective activities in neuronal
      cell cultures in response to various neurotoxins, as well as in vivo (e.g., in
      response to global ischemia, neurotrauma, head injury, anoxia, etc.), indicating
      that MAO inhibition is not a prerequisite for neuroprotection. The
      neuroprotective activity of these drugs has been demonstrated to be associated
      with the propargylamine moiety, which protects mitochondrial viability and
      mitochondrial permeability transition pore by activating Bcl-2 and downregulating
      the Bax family of proteins. Rasagiline processes amyloid precursor protein (APP)
      into the neuroprotective-neurotrophic soluble APPalpha (sAPPalpha) by protein
      kinase C- and mitogen-activated protein kinase-dependent activation of alpha
      secretase, and increases nerve growth factor, glial cell- derived neurotrophic
      factor (GDNF) and brain-derived neurotrophic factor (BDNF) expression and
      proteins. Thus, rasagiline may induce neuroprotection, neuroplasticity and long
      term potentiation. Rasagiline has therefore been chosen by the National
      Institutes of Health (NIH) to study its neuroprotective effects in
      neurodegenerative diseases. Long-term studies are required to evaluate the drug's
      disease-modifying prospects in Parkinson's and Alzheimer's diseases.

PMID- 16110344
TI  - Evidence of a double-lid movement in Pseudomonas aeruginosa lipase: insights from
      molecular dynamics simulations.
AB  - Pseudomonas aeruginosa lipase is a 29-kDa protein that, following the
      determination of its crystal structure, was postulated to have a lid that
      stretched between residues 125 and 148. In this paper, using molecular dynamics
      simulations, we propose that there exists, in addition to the above-mentioned
      lid, a novel second lid in this lipase. We further show that the second lid,
      covering residues 210-222, acts as a triggering lid for the movement of the
      first. We also investigate the role of hydrophobicity in the movement of the lids
      and show that two residues, Phe214 and Ala217, play important roles in lid
      movement. To our knowledge, this is the first time that a double-lid movement of
      the type described in our manuscript has been presented to the scientific
      community. This work also elucidates the interplay of hydrophobic interactions in
      the dynamics, and hence the function, of an enzyme.

PMID- 16110346
TI  - Posaconazole.
AB  - Invasive fungal infections are occurring with increasing frequency secondary to
      medical advances in the areas of transplantation, cancer management and
      autoimmune diseases. Unfortunately, the currently available antifungal
      armamentarium does not meet the increasing needs of managing infection in these
      complex patient populations. Posaconazole, a new triazole antifungal agent, is
      being investigated for its role in treating serious infections due to yeasts and
      molds. This new drug offers an expanded spectrum of activity over other members
      of its class. In addition to potent activity against fluconazole-resistant
      Candida and refractory cases of aspergillosis, posaconazole demonstrates activity
      against Zygomycetes. Posaconazole is a well-tolerated agent that offers a
      diminished toxicity profile compared with other currently marketed systemic
      antifungal agents. Clinical success rates thus far have been promising, although
      the exact role of this agent in treating and preventing invasive fungal
      infections is yet to be determined.

PMID- 16110347
TI  - Multimodal effects of available drugs for ischemic stroke.
AB  - Recent research demonstrates the complexity and variety of pathophysiologic
      processes underlying cerebral ischemia. This review will focus on the multimodal
      effects of the various drugs currently used for stroke prevention. The most
      recent clinical studies of each will also be reviewed, and the implications for
      clinical use and future research discussed. An evolving approach for stroke
      prevention will include a combination of antiplatelets, increased use of statins,
      ACE inhibitors and possibly vitamin therapy.

PMID- 16110348
TI  - Drug-induced sialorrhea.
AB  - Only a few drugs can induce drooling (sialorrhea or hypersalivation) to a
      clinically significant degree. When significant drooling occurs, however, it can
      pose a vexing management problem. Drooling is either caused by an increase in
      saliva flow that cannot be compensated for by swallowing, or by impaired
      swallowing that cannot handle normal or even reduced amounts of saliva. Major
      medication groups that are clearly associated with drooling are antipsychotics,
      particularly clozapine, and direct and indirect cholinergic agonists that are
      used to treat dementia of the Alzheimer type and myasthenia gravis. Drooling is
      also caused by certain heavy metal toxins (mercury and thallium); from exposure
      to irreversible acetylcholinesterase inhibitors (insecticides and nerve agents);
      and by a handful of other drugs (e.g., yohimbine, mucosa-irritating antibiotics).
      The treatment of medication-induced drooling is often only symptomatic and
      attempts to decrease saliva to amounts that can be swallowed (to prevent "pool
      and drool"). Most pharmacological approaches reduce cholinergic tone, either
      systemically (e.g., atropine-related oral anticholinergics) or more locally
      (e.g., sublingual ipratropium spray); or increase adrenergic tone (e.g.,
      clonidine patch). Recently, botulinum injections into the parotid gland have been
      used successfully to treat refractory cases.

PMID- 16110349
TI  - Executive summary: nicotine addiction.
AB  - Nicotine addiction is one of the most prevalent addictive behaviors worldwide.
      According to the World Health Organization (WHO), 1.3 billion men, women and
      children worldwide are smokers. In spite of increased awareness and action on the
      part of both governments and individuals, tobacco continues to be the leading
      cause of preventable disease and death in the United States, as well as in many
      other countries. According to WHO, there are nearly 5 million tobacco-related
      deaths worldwide each year and nearly half of the smokers in the world today will
      die as a result of their addiction. For individuals who are motivated to quit
      smoking, a combination of pharmacotherapy and behavioral therapy has been shown
      to be most effective in controlling the symptoms of nicotine withdrawal. Drugs
      marketed as smoking cessation aids include nicotine replacement therapy (NRT) and
      sustained-release bupropion hydrochloride. New drugs in development are directed
      to targets including nicotinic acetylcholine receptors, cannabinoid receptors,
      dopamine receptors and opioid receptors. Several therapeutic vaccines are also in
      the pipeline.

PMID- 16110350
TI  - FISH studies of chromosome abnormalities in germ cells and its relevance in
      reproductive counseling.
AB  - Chromosome abnormalities are one of the major causes of human infertility. In
      infertile males, abnormal karyotypes are more frequent than in the general
      population. Furthermore, meiotic disorders affecting the germ cell-line have been
      observed in men with normal somatic karyotypes consulting for infertility. In
      both cases, the production of unbalanced spermatozoa has been demonstrated.
      Basically addressed to establish reproductive risks, fluorescence in situ
      hybridization (FISH) on decondensed sperm heads has become the most frequently
      used method to evaluate the chromosomal constitution of spermatozoa in carriers
      of numerical sex chromosome abnormalities, carriers of structural chromosome
      reorganizations and infertile males with normal karyotype. The aim of this review
      is to present updated figures of the information obtained through sperm FISH
      studies with an emphasis on its clinical significance. Furthermore, the
      incorporation of novel FISH-based techniques (Multiplex-FISH; Multi-FISH) in male
      infertility studies is also discussed.

PMID- 16110351
TI  - Identification of potential biomarkers of Peyronie's disease.
AB  - AIM: To identify proteins that are differentially expressed in cells derived from
      normal and diseased tunica albuginea (TA) as related to Peyronie's disease (PD).
      METHODS: Cells with characteristics of fibroblasts were isolated from two tissue
      sources. Those from the plaque of patients with PD were designated as PT cells,
      and those from the normally-appearing TA of the same patients were designated as
      NT cells. Messenger RNAs of these cells were analyzed by real-time polymerase
      chain reaction (RT-PCR) for the expression of monocyte chemoattractant protein 1
      (MCP-1). Crude protein lysates were analyzed by surface-enhanced laser
      desorption/ionization mass spectrometry (SELDI-MS) with IMAC30-Cu, CM10, and H50
      chips. Each lysate was then separated into six fractions, which were further
      analyzed by SELDI-MS. RESULTS: RT- PCR analysis showed that PT cells expressed
      higher levels of MCP-1 than their counterpart NT cells. SELDI-MS analysis showed
      that the crude protein lysates of all four cell strains produced similar and
      reproducible protein profiles on IMAC30-Cu and CM10 chips. Additional SELDI-MS
      analyses with the fractionated lysates detected three proteins of 11.6 kDa, 14.5
      kDa, 22.6 kDa that were upregulated in PT cells and two proteins of 6.3 kDa and
      46.9 kDa that were downregulated in PT cells. CONCLUSION: MCP-1, which is often
      involved in tissue fibrosis, was expressed at higher levels in PT than that in NT
      cells. Five potential biomarkers for PD were identified by SELDI-MS analysis.

PMID- 16110352
TI  - Expression of a novel dipeptidyl peptidase 8 (DPP8) transcript variant, DPP8-v3,
      in human testis.
AB  - AIM: To investigate the role of a novel dipeptidyl peptidase 8 transcript variant
      (DPP8-v3) gene in testis development and/or spermatogenesis. METHODS: A human
      testis cDNA microarray was hybridized with mRNA of human adult and fetal testes.
      Differentially expressed clones were sequenced and characterized and their
      expression was analyzed by real-time reverse transcription polymerase chain
      reaction (RT-PCR) and Southern-blot analysis. RESULTS: A new transcript variant
      of the human dipeptidyl peptidase (DPP8), exhibiting a 5-fold higher expression
      level in human adult than that in fetal testes, was cloned and was named DPP8
      variant 3 (DPP8-v3). The full-length sequence of DPP8-v3 was 3,030 bp, encoding a
      protein of 898 amino acids. CONCLUSION: DPP8-v3 is a novel human DPP8 transcript
      variant highly expressed in the adult testis. Similar to DPPIV, DPP8-v3 may play
      a key role in the immunoregulation of testes and accordingly may influence
      spermatogenesis and male fertility.

PMID- 16110353
TI  - Combined conventional/antioxidant "Astaxanthin" treatment for male infertility: a
      double blind, randomized trial.
AB  - AIM: To evaluate the treatment of male infertility with a strong natural
      antioxidant, in addition to conventional treatment. METHODS: Using a double
      blind, randomized trial design, 30 men with infertility of > or =2 months and
      female partners with no demonstrable cause of infertility received conventional
      treatment according to the guidelines of the World Health Organization (WHO), and
      either a strong antioxidant Astaxanthin 16 mg/day (AstaCarox, AstaReal AB,
      Gustavsberg, Sweden) or placebo for 3 months. The effects of treatment on semen
      parameters, reactive oxygen species (ROS), zona-free hamster oocyte test, serum
      hormones including testosterone, luteinizing hormone (LH), follicle stimulating
      hormone (FSH) and Inhibin B, and spontaneous or intrauterine insemination (IUI)
      induced pregnancies were evaluated. RESULTS: ROS and Inhibin B decreased
      significantly and sperm linear velocity increased in the Astaxanthin group (n =
      11), but not in the placebo group (n = 19). The results of the zona-free hamster
      oocyte test tended to improve in the Astaxanthin group in contrast with the
      placebo group, though not reaching statistical significance. The total and per
      cycle pregnancy rates among the placebo cases (10.5 % and 3.6 %) were lower
      compared with 54.5 % and 23.1 % respectively in the Astaxanthin group (P = 0.028;
      P = 0.036). CONCLUSION: Although the present study suggests a positive effect of
      Astaxanthin on sperm parameters and fertility, the results need to be confirmed
      in a larger trial before recommending Astaxanthin for the complementary treatment
      of infertile men.

PMID- 16110354
TI  - Does exposure to computers affect the routine parameters of semen quality?
AB  - AIM: To assess whether exposure to computers harms the semen quality of healthy
      young men. METHODS: A total of 178 subjects were recruited from two maternity and
      children healthcare centers in Shanghai, 91 with a history of exposure to
      computers (i.e., exposure for 20 h or more per week in the last 2 years) and 87
      persons to act as control (no or little exposure to computers). Data on the
      history of exposure to computers and other characteristics were obtained by means
      of a structured questionnaire interview. Semen samples were collected by
      masturbation in the place where the semen samples were analyzed. RESULTS: No
      differences in the distribution of the semen parameters (semen volume, sperm
      density, percentage of progressive sperm, sperm viability and percentage of
      normal form sperm) were found between the exposed group and the control group.
      Exposure to computers was not found to be a risk factor for inferior semen
      quality after adjusting for potential confounders, including abstinence days,
      testicle size, occupation, history of exposure to toxic substances. CONCLUSION:
      The present study did not find that healthy men exposed to computers had inferior
      semen quality.

PMID- 16110355
TI  - Regionalization of epididymal duct and epithelium in rats and mice by automatic
      computer-aided morphometric analysis.
AB  - AIM: To establish a rat and mouse epididymal map based on the use of the
      Epiquatre automatic software for histologic image analysis. METHODS: Epididymides
      from five adult rats and five adult mice were fixed in alcoholic Bouin's fixative
      and embedded in paraffin. Serial longitudinal sections through the medial aspect
      of the organ were cut at 10 microm and stained with hematoxylin and eosin. As
      determined from major connective tissue septa, nine subdivisions of the rat
      epididymis and seven for the mouse were determined, consisting of five sub
      regions in the caput (rat and mouse), one (mouse) or three (rat) in the corpus
      and one in the cauda (rat and mouse). Using the Epiquatre software, several
      tubular, luminal and epithelial morphometric parameters were evaluated. RESULTS:
      Statistical comparison of the quantitative parameters revealed regional
      differences (2-5 in the rat, 3-6 in the mouse, dependent on parameters) with
      caput regions 1 and 2 being largely distinguishable from the similar remaining
      caput and corpus, which were in turn recognizable from the cauda regions in both
      species. CONCLUSION: The use of the Epiquatre software allowed us to establish
      regression curves for different morphometric parameters that can permit the
      detection of changes in their values under different pathological or experimental
      conditions.

PMID- 16110356
TI  - Expression of a novel alternative transcript of the novel retinal pigment
      epithelial cell gene NORPEG in human testes.
AB  - AIM: To identify a novel alternative transcript of the novel retinal pigment
      epithelial cell gene (NORPEG) expressed in the human testis. METHODS: A human
      testis cDNA microarray was established and hybridized with cDNA probes from human
      fetal testes, adult testes and human spermatozoa. Differentially expressed clones
      were sequenced and analyzed. One of these clones was a short transcript of NORPEG
      which we proceeded to analyze by RT-PCR. RESULTS: The novel short alternative
      transcript of NORPEG was isolated and named sNORPEG. It was 3486 bp in length and
      contained a 2952-bp open reading frame, encoding a 110.4-kDa protein of 983 amino
      acids. Amino acid sequence analysis showed that the sNORPEG protein contains six
      ankyrin repeats and two coiled-coil domains. It shares a high homology with the
      NORPEG and ankycorbin proteins in both its sequence and motifs. Blasting the
      human genome database localized sNORPEG to human chromosome 5p13.2-13.3.
      Expression profiles showed that sNORPEG was expressed in human fetal testes,
      adult testes and spermatozoa. Moreover, sNORPEG was found to be ubiquitously
      expressed in human tissues. CONCLUSION: sNORPEG is expressed in different
      developmental stages of the testis and encodes a protein that may have roles in
      human testis development and spermatogenesis.

PMID- 16110357
TI  - Testicular fine needle aspiration as a diagnostic tool in non-obstructive
      azoospermia.
AB  - AIM: To report the fine needle aspiration cytology (FNAC) of the testes used as a
      diagnostic tool in non-obstructive azoospermic patients. METHODS: One hundred and
      twenty-five non-obstructive azoospermic male candidates to intracytoplasmic sperm
      injetion (ICSI) were analysed for follicle stimulating hormone (FSH), luteinizing
      hormone (LH), testosterone and inhibin B plasma levels. They were classified into
      three groups on the basis of FNAC: 1) Sertoli cell-only syndrome (SCOS) (70); 2)
      severe hypospermatogenesis (42); and 3) maturation arrest (13). Then, all men
      underwent testicular sperm extraction (TESE) for sperm recovery for ICSI.
      RESULTS: Mature spermatozoa were detected by FNAC in 24 of 42 men with severe
      hypospermatogenesis and nine of 13 men with maturation arrest; while they were
      retrieved by TESE in 29 of 70 men with SCOS, 35 of 42 men with severe
      hypospermatogenesis (including the 24 by FNAC) and 10 of 13 men with maturation
      arrest (including the nine by FNAC). The sensitivity and specificity of FNAC were
      44.6 % and 100 %, respectively. There was no difference on testicular volume and
      hormonal parameters in men with and without sperm retrieved. CONCLUSION: These
      findings suggest that FNAC may be a simple and valid diagnostic parameter in non
      obstructive azoospermic men and it may represent a valid positive prognostic
      parameter for sperm recovery at TESE.

PMID- 16110358
TI  - Localization and potential function of androgen receptor in rat salivary gland.
AB  - AIM: To investigate the localization and quantity of androgen receptor (AR) in
      the salivary glands of rats with further analysis on the effect of castration.
      METHODS: Sixty male Wistar rats, aged 30-60 days, were randomly divided into
      three groups (castrated, sham-operated and normal controls) with 20 rats in each
      group. The rats in the castrated group were castrated and the submaxillary glands
      were removed after 1 week. The salivary glands of the rats in the sham-operated
      and the normal control groups were also removed. Parts of the salivary glands
      were fixed for immunohistochemistry and in situ hybridization assays. Other parts
      were used for Western blot. RESULTS: AR immunoreactivity in the three groups was
      localized in the glandular epithelial cells of the serous acinus and the
      glandular duct of the salivary gland, mainly in the nuclei. AR mRNA hybridization
      signals in the salivary glands of the castrated group were mainly distributed in
      the epithelial cells of the convoluted and secretary ducts; AR mRNA in the sham
      operated and the normal control groups were found in the epithelial cells of the
      convoluted, the secretary and the excretory ducts. The quantity of AR in the
      salivary glands was decreased significantly in the castrated rats compared with
      the sham-operated and the normal controls. Moreover, epidermal growth factor
      (EGF) secreted by the salivary glands was also decreased in the castrated rats.
      CONCLUSION: Castration appears to affect the production of AR in the salivary
      gland and the distribution of the AR mRNA and could further affect the function
      of the salivary gland. The changes of AR and the distribution of AR mRNA may play
      an important role in the interactions between the testes and the salivary gland.

PMID- 16110359
TI  - Effects on the quality of frozen-thawed alpaca (Lama pacos) semen using two
      different cryoprotectants and extenders.
AB  - AIM: To evaluate two extenders and two cryoprotectant agents (CPA) for alpaca
      semen cryopreservation. METHODS: Semen samples were obtained from four adult
      alpacas (Lama pacos) and frozen using extender I (TRIS, citrate, egg yolk and
      glucose) or extender II (skim milk, egg yolk and fructose), each containing
      either glycerol (G) or ethylene glycol (EG) as CPA. Consequently, four groups
      were formed: 1) extender I-G; 2) extender I-EG; 3) extender II-G; and 4) extender
      II-EG. Semen was diluted in a two-step process: for cooling to 5 degrees
      (extenders without CPA), and for freezing (extenders with CPA). Viability and
      acrosome integrity were assessed using trypan blue and Giemsa stains. RESULTS:
      When compared, the motility after thawing was higher (P >0.05) in groups II-EG
      (20.0% +/- 6.7%) and II-G (15.3 % +/- 4.1% ) than that in groups I-G (4.0 % +/-
      1.1%) and I-EG (1.0 % +/- 1.4%). Viable spermatozoa with intact acrosomes in
      groups II-EG (18.7 % +/- 2.9%) and II-G (12.7 % +/- 5.9%) were higher than that
      in groups I-G (5.7% +/- 1.5%) and I-EG (4.0% +/- 1.0%). CONCLUSION: The skim milk
      and egg yolk-based extenders containing ethylene glycol or glycerol to freeze
      alpaca semen seems to promote the survival of more sperm cells with intact
      acrosomes than the other extenders.

PMID- 16110360
TI  - Effects of tamoxifen citrate on gene expression during nuclear chromatin
      condensation in male rats.
AB  - AIM: To evaluate the effects of tamoxifen citrate on gene expression during
      nuclear chromatin condensation in male rats. METHODS: The effects of an oral dose
      of 0.4 kg/(kg.d) tamoxifen citrate on rates of in vitro chromatin decondensation,
      acridine orange (AO) dye uptake, concentration of thiol-groups, levels and/or
      expression of transition proteins 1, 2 (TP1, TP2), protamine 1 (P1), cyclic AMP
      response element modulator-tau (CREMtau), androgen-binding protein (ABP) and
      cyclic adenosine 3',5' monophosphate (cAMP) were evaluated after 60 days of
      exposure in adult male rats. Controls received the vehicle. RESULTS: Tamoxifen
      citrate enhanced the rates of chromatin decondensation, increased AO dye uptake
      and reduced free thiols in caput epididymal sperms and reduced the levels of TP1,
      TP2, P1, and CREMtau in the testis, while cAMP was unaffected. P1 deposition was
      absent in the sperm. The transcripts of TP1, TP2 were increased, of P1 and ABP
      decreased, while those of CREMtau unaffected in the testis. CONCLUSION: Tamoxifen
      citrate reduced caput epididymal sperm chromatin compaction by reducing the
      testicular levels of proteins TP1, TP2 and P1 and the CREMtau involved in
      chromatin condensation during spermiogenesis. Tamoxifen citrate affects the
      expression of these genes at both the transcriptional and post-transcriptional
      levels.

PMID- 16110361
TI  - Measurement of serum zinc improves prostate cancer detection efficiency in
      patients with PSA levels between 4 ng/mL and 10 ng/mL.
AB  - AIM: To investigate whether the measurement of serum zinc may improve the
      detection of prostate cancer (PCa) in men who had total prostate-specific antigen
      (PSA) levels higher than 4.1 ng/mL. METHODS: A mass screening for PCa of 3940 men
      over 50 years old was undertaken using total serum PSA. Of the 190 men (4.8%)
      with elevated PSA, 143 (3.6%) underwent a transrectal ultrasonography (TRUS)
      guided biopsy of the prostate, and 42 men (1% of total and 29.3% of men
      undergoing biopsy) were found to have cancer. The areas under the receiver
      operating characteristic curves (ROC-AUC) were used to compare the diagnostic
      power of cancer detection by means of serum zinc, and free PSA/total PSA ratio
      (f/t). RESULTS: The men with levels of serum zinc that ranged from 40 ng/mL-60
      ng/mL, had an age-adjusted odds ratios(OR) of 5.0. A cutoff value of 100
      microg/mL for serum zinc concentration provided a sensitivity of 90.5% and a
      specificity of 32.7% in elevated PSA range, and a sensitivity of 93.3% and
      specificity of 27.1% in gray zone, respectively. In the gray zone ranges of 4.1
      ng/mL-10.0 ng/mL, the ROC-AUC for zinc was 73.0% higher than 62.7% of f/t PSA
      ratio and 56.7% of total PSA. CONCLUSION: PCa displays a lower serum zinc
      concentration. The measurement of zinc levels improves PCa detection in the gray
      zone compared with the f/t PSA ratio and total PSA.

PMID- 16110362
TI  - Tuberculous epididymitis: a case report and literature review.
AB  - Tuberculous epididymitis is a rare urological disease difficult to diagnose. The
      conventional methods for diagnosis are often time-consuming and invasive. The
      combined use of scrotal magnetic resonance imaging (MRI) and urinary polymerase
      chain reaction (PCR)-based assay for mycobacterial DNA (the latter because of its
      high sensitivity and specificity to demonstrate mycobacterial DNA) is a valuable
      method for rapid diagnosis of tuberculous epididymitis. We report a 79-year-old
      man who was admitted with the chief complaints of bilateral scrotal swelling and
      pain. The combined use of scrotal MRI and urinary PCR allowed prompt diagnosis of
      tuberculous epididymitis and adequate antituberculous therapy.

PMID- 16110364
TI  - Carotid stenting.

PMID- 16110365
TI  - What are the key factors in setting up a successful carotid stent program?
AB  - Carotid stenting will drastically alter the management of carotid bifurcation
      stenosis. Key factors to include when initiating a carotid stent program are
      discussed. Questions addressed include the following: Who has clinical
      responsibility for patients with carotid disease? What is the rationale for a
      carotid stent program? How does one initiate a carotid stent program? How does
      one deal with endovascular realities? Training, patient selection, quality
      improvement, and proctoring are also reviewed.

PMID- 16110366
TI  - Commentary on "What are the key factors in setting up a successful carotid stent
      program?".

PMID- 16110368
TI  - What are the skills that prepare vascular surgeons for carotid stenting?
AB  - Although it has been clearly established that in certain groups of patients, such
      as in patients with symptomatic high-grade carotid stenosis and in selected
      asymptomatic patients with high-grade stenosis, carotid endarterectomy offers
      significant protection from stroke compared with medical therapy, the role of
      carotid stenting in this patients versus carotid endarterectomy is undergoing a
      rapid evolution. The definitive evidence awaits the results of ongoing
      prospective, randomized trials such as CREST and others, but it is clear that
      carotid stenting will increasingly occupy a significant role in the therapy of
      carotid bifurcation disease. In that context, vascular surgeons, traditionally
      the experts on the management of this condition, face the specter of other
      disciplines intervening in its treatment. In addition, if vascular surgeons do
      not acquire the skills and the expertise necessary to perform carotid stenting,
      it is self-evident that they run the risk of being spectators rather retaining
      the mantle of expert in the management of carotid bifurcation disease. As such,
      it is the duty of vascular surgeons to acquire the skills with which to retain
      their rightful place in its management and treatment. The purpose of this article
      is to describe the skills necessary to become competent in the endovascular
      management of carotid disease, offer some thoughts and strategy by which one can
      gain experience and develop an armamentarium of skills necessary to perform
      carotid stenting, and offer a comprehensive array of options of management and
      treatment to the patient with carotid disease.

PMID- 16110369
TI  - Commentary on "What are the skills that prepare vascular surgeons for carotid
      stenting?".

PMID- 16110372
TI  - Commentary on "Establishing sheath access for carotid interventions: tips and
      pitfalls".

PMID- 16110371
TI  - Establishing sheath access for carotid interventions: tips and pitfalls.
AB  - Carotid angioplasty and stenting requires delivery of therapy through a sheath
      rather than open vascular access. Safe and successful sheath delivery facilitates
      the carotid angioplasty and stenting procedure and depends upon an ability to
      assess the aortic arch, catheterize its branches, perform remote access guidewire
      catheter manipulation, and place a sheath.

PMID- 16110374
TI  - What is the learning curve for carotid artery stenting with neuroprotection?
      Analysis of 200 consecutive cases at an academic institution.
AB  - Carotid artery stenting (CAS) has emerged as an acceptable treatment alternative
      in high-risk patients with carotid stenosis. This study assessed the effect of
      the learning curve on treatment complications and clinical outcome of CAS.
      Clinical variables and treatment outcomes of 200 consecutive CAS procedures in
      182 patients (mean age, 72 years) with carotid stenosis of 70% or greater during
      a 40-month period were analyzed. Technical success, periprocedural complications,
      and treatment outcomes were compared in four sequential groups (group I, II, III,
      and IV) of 50 consecutive interventions. Treatment indications and relevant risk
      factors were similar among the four groups. The overall technical success was
      98%, and the combined 30-day stroke and death rates was 2.5%. An increase in the
      technical success rate was noted in the latter three groups compared with group I
      (P < .05). Total procedural time and contrast volume were significantly higher in
      group I compared with the latter three groups (P < .05). The intraoperative
      anticoagulation regimen was changed from an intravenous heparin combination to
      bivalirudin after the first 54 cases, resulting in reduced bleeding complications
      in groups III and IV (P = .03) compared with group I. The 30-day stroke and death
      rate in groups I and II was 8% and 2%, which was reduced significantly to 0% in
      groups III and IV (P < .05). A Cox regression model identified procedural volume
      (P = .03) as a predictor of a reduced complication rate. Carotid artery stenting
      with neuroprotection can provide excellent treatment outcome. Our experience
      demonstrates a procedural-associated learning curve, as evidenced by the reduced
      procedural-related complications, fluoroscopic time, and contrast volume that
      occurred with an increase in physician experience. The procedural success is also
      enhanced partly by endovascular device refinement and improved anticoagulation
      regimen. Successful outcome of CAS can be achieved once physicians overcome the
      initial procedural-related learning curve.

PMID- 16110375
TI  - Commentary on "What is the learning curve for carotid artery stenting with
      neuroprotection? Analysis of 200 consecutive cases at an academic institution".

PMID- 16110377
TI  - Credentialing for carotid artery stenting.
AB  - Endovascular treatment of cervical carotid artery stenosis is a rapidly expanding
      area of clinical competence, and physicians from various subspecialties are
      already performing carotid artery stenting. As a result of the diverse specialty
      backgrounds of physicians performing carotid artery stenting, consensus regarding
      the establishment of credentialing standards remains elusive. In the following
      manuscript we review the physician credentialing process, published data, and
      national society position statements applicable to carotid artery stenting.

PMID- 16110378
TI  - Commentary on "Credentialing for carotid artery stenting: expert commentary".

PMID- 16110380
TI  - What is the latest in inventory for carotid stenting and cerebral protection?
AB  - Carotid angioplasty is fast being incorporated into the treatment options for
      patients with carotid occlusive disease. The results of the SAPPHIRE and ARCHER
      trials have demonstrated that carotid angioplasty and stenting with the use of
      cerebral protection devices is not inferior to open surgical endarterectomy in
      high-risk patients. The limiting step for percutaneous carotid interventions was
      the potential for cerebral embolization during the intervention. However, the
      ready availability of several embolic protection devices has placed this
      technology into the hands of many endovascular specialists. A brief outline of
      the basic inventory necessary for a carotid stent program is presented.

PMID- 16110381
TI  - Commentary on "What is the latest in inventory for carotid stenting and cerebral
      protection?".

PMID- 16110383
TI  - The vascular surgeon's role in risk factor modification: results of a survey.
AB  - PURPOSE: Comprehensive care of vascular patients includes attention to
      atherosclerotic risk factor management. We surveyed members of the Midwestern
      Vascular Surgical Society (MVSS) with the following objectives: (1) to determine
      the usual practice pattern with respect to risk factor inquiry, screening, and
      intervention, (2) to determine which risk factors vascular surgeons believe are
      important for patients with peripheral arterial disease, and (3) to determine the
      vascular surgeon's confidence for management of each risk factor. METHODS: A
      survey was mailed to all MVSS members and two additional notifications were sent
      for initial nonresponders. Data regarding practice environment and local
      resources available to each surgeon were recorded. Questions were designed to
      determine the prevalence of risk factor inquiry and screening, grading of the
      importance of each risk factor, and the vascular surgeon's confidence in the
      management of each risk factor. RESULTS: The survey was completed by 219 (56%) of
      391 of MVSS members. The average age of the responders was 53.1 +/- 9.3 years,
      and 94.1% were men. Seventy-four percent of the surgeons dedicate 90% to 100% of
      their time to vascular surgery, and 89% dedicate more than 50%. Seventy-seven
      percent of responders work in a private institution and 23% in a public hospital.
      The surgeon's practice had a full- or part-time affiliation with a medical school
      in 62% and was entirely community-based in 38%. A high proportion of surgeons
      inquire about each risk factor, but only a minority performs the actual screening
      of the risk factors, with the exception of hypertension. Diabetes mellitus and
      smoking were believed to be very important risk factors, hypertension and lipids
      of moderate importance, and exercise and activity, nutrition, and homocysteine
      level of low importance. The surgeons' confidence in risk factor management was
      low to moderate for most risk factors, but high for smoking and exercise. Despite
      these responses, only 10% of vascular surgeons thought that they should be
      primarily responsible for risk factor management. CONCLUSIONS: Vascular surgeons
      must provide a comprehensive approach to risk factor management for their
      patients. This can be conducted through the establishment of multidisciplinary
      risk factor programs or by the surgeon in certain cases when outside resources
      are not available. Risk factor management must be emphasized in vascular
      continuing medical education programs to enable surgeons to be confident with
      management.

PMID- 16110384
TI  - Arteriovenous access: managing common problems.
AB  - The creation and maintenance of hemoaccess occupies a significant portion of most
      vascular and general surgery practices. In this article, the methods used to
      detect hemoaccess at risk for failure and the endovascular and surgical
      techniques used to prolong or restore their patency are reviewed. Also, the
      management of hemoaccess infection, aneurysmal degeneration, false aneurysm
      formation, and symptomatic arterial steal syndrome are described.

PMID- 16110385
TI  - An algorithm for diagnosis and treatment of type II endoleaks and endotension
      after endovascular aneurysm repair.
AB  - Endoleak after endoluminal abdominal aortic aneurysm repair is a relatively
      common occurrence. Depending on the type of endoleak involved, treatment
      strategies range from continued serial observation to urgent re-intervention.
      Type II, or branch vessel endoleaks, are often benign in terms of their natural
      history but can potentially be associated with progressive abdominal aortic
      aneurysm sac expansion, endograft migration, or even aneurysm rupture. Type V
      endoleaks, also known as endotension, may represent an undiagnosed type I-IV
      endoleak or a progressive accumulation of transudate through the interstices of
      the endograft. Treatment strategies therefore hinge on correctly identifying the
      etiology of the endotension. We discuss the diagnosis and management of type II
      and V endoleaks, with a focus on a device-specific approach to endoleak
      treatment.

PMID- 16110386
TI  - Commentary. Association between long-term statin use and mortality after
      successful aneurysm surgery.

PMID- 16110388
TI  - Commentary. Cognitive impairment and decline are associated with carotid artery
      disease in patients without clinically evident cerebrovascular disease.

PMID- 16110390
TI  - Commentary. Validity of exam assessment of surgical skills EBSQ/VASC pilot study.

PMID- 16110395
TI  - Commentary. Sexual dysfunction after conventional and endovascular AAA repair:
      results of the DREAM trial.

PMID- 16110392
TI  - Commentary. Low-molecular-weight heparin as bridging anticoagulation during
      interruption of warfarin: assessment of a standardized periprocedural
      anticoagulation regimen.

PMID- 16110396
TI  - Commentary. Effect of chronic kidney disease on outcomes after carotid artery
      stenting.

PMID- 16110398
TI  - Commentary. Accuracy of computed tomographic angiography and magnetic resonance
      angiography for diagnosing renal artery stenosis.

PMID- 16110401
TI  - Commentary. Coronary artery revascularization before elective major vascular
      surgery.

PMID- 16110405
TI  - [Obstructive uropathy in childhood].
AB  - "Obstructive uropathy" is a generic term which combines different diseases in
      infants and childhood. Both the upper and lower urinary tract may be affected.
      Diseases of the urinary tract can cause an intrinsic obstruction. Sometimes
      tumours may cause a compression and as secondary effect an obstruction
      (extrinsic). Ultrasound is the key diagnostic tool and shows dilatation of the
      obstructed urinary tract. But for the functional exploration of babies and
      toddlers, renal scanning and X-ray examinations are necessary. These examinations
      lead to an exposure to radiation which necessitates careful indication. Some of
      the congenital diseases (for example ureteropelvic junction obstruction,
      megaureter) show a maturation without any intervention. So one has to decide
      whether to wait and see or to operate. A percutaneous nephrostomy or a DJ
      catheter is not often used in the treatment of obstruction in general. These
      forms of drainage are more often used in the treatment of stones or of extrinsic
      obstruction. A pyelocutaneostomy or ureterocutaneostomy is a special surgical
      procedure in pediatric urology for transient drainage of the upper urinary tract
      (megaureter). The operation of a seriously ill new-born should be done in a
      centre for pediatric urology and pediatric nephrology. When the upper urinary
      tract is dilated, patients may need an antibiotic prophylaxis, because the
      dilatation of the upper urinary tract increases the risk of urinary tract
      infections (UTI). The indication for antibiotic prophylaxis should by guided by
      the criteria of the APN-Consensus Paper. Long-term follow-up is necessary and
      should comprise ultrasound, physical examination, controlling the blood pressure,
      urine analysis and blood tests. The aims of diagnostics, treatment and long-term
      follow-up are the preservation of renal function and to protect the children from
      UTI. This goal must be reached under conditions that are appropriate for children
      and their parents.

PMID- 16110406
TI  - [Obstructive uropathy in adults].
AB  - Urinary tract obstruction is a common clinical problem. The obstruction of the
      urinary flow may be acute or chronic, partial or complete, unilateral or
      bilateral, and may occur at any site of the urinary tract. The major causes of
      urinary tract obstruction vary with the age of the patient. Anatomic
      abnormalities, e. g. ureteropelvic junction obstruction, account for the majority
      of cases in children. In comparison, calculi are most common in young adults,
      while prostatic hyperplasia or carcinoma, retroperitoneal or pelvic neoplasms,
      and calculi are the primary causes in older patients. Urinary tract obstruction
      results in different pathophysiological changes causing various symptoms. In
      addition to the aetiology, pathophysiology and clinical presentation of
      obstructive uropathy in adults, modern diagnostic and therapeutic options are
      presented in this review.

PMID- 16110407
TI  - [Intravesical adjuvant chemotherapy for superficial bladder cancer -- results of
      a survey in Saxony].
AB  - For patients with superficial bladder cancer, adjuvant intravesical chemotherapy
      or immunotherapy with Bacillus Calmette-Guerin (BCG) is recommended in national
      and international guidelines. We analyzed whether the recommended therapeutic
      regimens are used in daily urological practice. Questionnaires concerning the
      adjuvant intravesical therapy were sent to 152 urologists in the German Federal
      State of Saxony. Of the surveyed physicians, 134 practiced in an outpatient
      medical facility and 18 in a hospital. Of the questionnaires, 73 (48.02 %) were
      returned and evaluated. An adjuvant intravesical therapy after transurethral
      bladder tumor resection was performed in every second patient (median value 50.07
      %). The majority of the urologists (79.4 %) treated the bladder tumors with
      intravesical chemotherapy or BCG depending on tumor stage and grade of
      malignancy. Chemotherapeutic agents or BCG was exclusively used in 13.6 % and 4.1
      % of treated patients, respectively. Chemotherapeutic agents were predominantly
      applied up to the primary tumor stage T1 and malignancy grade G2. In cases with
      recurrent T1 bladder tumors of G2 or higher grade of malignancy, BCG was the main
      agent for intravesical treatment. In patients with recurrent T1G3 tumors, the
      majority of urologist (57.1 %) preferred another therapeutic regimen than
      intravesical instillation. Only 23.2 % of the urologists believed that
      intravesical BCG is superior to chemotherapeutic agents. These data demonstrate
      that adjuvant intravesical instillation with chemotherapeutic agents and BCG is
      well established in urological practice. In contrast to the recommendations of
      national and international guidelines, chemotherapeutic agents are more
      frequently used in cases with a high risk of progression.

PMID- 16110408
TI  - [Therapy of hormone refractory prostate cancer: new standards, new trends].
AB  - Hormone-refractory prostate cancer is diagnosed with increasing incidence and has
      become a growing challenge for urologists. The improved understanding of the
      tumor biological mechanisms of the hormone-refractory state has led to innovative
      therapeutic developments in the field of hormonal and cytotoxic therapies.
      Recently, two large randomized Phase III trials with docetaxel-based chemotherapy
      were able to show prolonged survival and a positive influence on pain and quality
      of life, establishing a new standard of care for these patients. Moreover,
      bisphosphonates seem to have positive influence on selected patients. In the
      growing field of molecular targeted therapy, first trials with compounds, such as
      tyrosine kinase inhibitors, anti-sense oligonucleotides, angiogenesis inhibitors
      and endothelin receptor antagonists, show promising results in the treatment of
      patients with hormone-refractory prostate cancer.

PMID- 16110409
TI  - [Retroperitoneal ganglioneuroma].
AB  - The ganglioneuroma is a benign neuroblastal tumor. All neuroblastomas and
      ganglioneuromas derive from immature cells of the sympathetic nerve system. The
      ganglioneuroma is a very rare disease and effects newborns and infants more often
      than adolescents and adults. The benign tumors are relatively difficult to
      diagnose since they usually are asymptomatic. A 5-year old girl with persistent
      bladder wall thickening and prominent course of the prevesical ureter presents
      for diagnosis and therapy. Sonography demonstrated a space-occupying lesion of
      the left kidney. Subsequent MRI raises the suspicion of a retroperitoneal
      neuroblastoma. The tumor could be removed in two surgical sessions. The
      ganglioneuroma is a benign tumor with symptoms depending on location and with a
      relatively good prognosis. Its low incidence and resultant limited experience
      often leads to delayed diagnosis, potentially determining therapy and diagnosis.

PMID- 16110414
TI  - [Position paper on medical expert opinion on silicosis].

PMID- 16110415
TI  - [Matrix metalloproteinases and their inhibitors in lung cancer with malignant
      pleural effusion].
AB  - Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases
      (TIMP) play a crucial role in physiological and pathological matrix turnover.
      This study aimed to determine the occurrence of MMP and TIMP in lung cancer
      patients with malignant pleural effusions (CA). METHODS: MMP-1, MMP-2, MMP-3, MMP
      8, MMP-9, TIMP-1, and IMP-2 oncentrations were determined by ELISA and zymography
      in pleural effusions and plasma of 31 CA and 14 congestive heart failure (CHF)
      patients and in plasma of 18 healthy controls (CON). RESULTS: MMP-2, TIMP-1, and
      TIMP-2 ELISA-concentrations were increased in CA pleural fluid vs. CA plasma (p <
      0.005, p < 0.005, p < 0.05), in contrast to MMP-9 being higher in plasma (p <
      0.005). Pleural fluid MMP-1 and MMP-8 were increased in CA vs. CHF (p < 0.05, p <
      0.005). MMP and TIMP plasma concentrations were not different in CA vs. CHF, but
      MMP-9, TIMP-1, and TIMP-2 were increased vs. CON (p < 0.005, each). Gelatine
      zymography MMP-9/MMP-2 ratios were increased in CA plasma vs. effusion fluid (p <
      0.005), in CA vs. CHF plasma, CA vs. CHF effusions (p < 0.005 each), and in CA
      vs. CON plasma (p < 0.05). CONCLUSIONS: MMP-2, TIMP-1, and TIMP-2 accumulate in
      the pleural compartment in CA and CHF, probably reflecting an unspecific pleural
      reaction. MMP-1 and MMP-8 are increased in cellular rich CA pleural effusions
      only. The determination of MMP-9/MMP-2 ratios in pleural fluid may contribute to
      differentiate CHF from CA effusions.

PMID- 16110416
TI  - [Non-passable tumor-associated stenosis of trachea and stent-implantation -- an
      indication for Virtual CT-bronchoscopy].
AB  - We report about a male 50-year-old patient with known non-small cell lung cancer
      and tumor-associated stenosis of the right main bronchus already treated with
      Neodym-YAG-laser coagulation. Eight months later the patient was readmitted to
      hospital and revealed complete occlusion of the right main bronchus and subtotal
      stenosis of the distal trachea and the left main bronchus. Conventional
      tracheobronchoscopy failed to visualize the post-stenotic parts of the left main
      bronchus due to the length and degree of stenosis. Multidetector-CT-generated
      virtual tracheobronchoscopy was able to demonstrate complete intraluminal tumor
      extent thus making precise pre-interventional measurements for stent implantation
      possible. Furthermore, post-interventional re-evaluation by virtual
      tracheobronchoscopy confirmed correct position and patency of the stent located
      within the distal trachea and the left main bronchus. Our case report
      demonstrates a non-invasive and easy approach for evaluating the tracheobronchial
      system in a patient with tumor-associated airway stenosis including the
      possibility for viewing beyond post-stenotic segments.

PMID- 16110417
TI  - [The face in not only coloured by blue blood].

PMID- 16110418
TI  - [Epidemiology and diagnostics of carcinoma of the lung -- Part 1].

PMID- 16110419
TI  - [Position paper of the German Society of Pneumology on medical expert opinion for
      silicosis].

PMID- 16110420
TI  - [Idiopathic interstitial pneumonias: pathomechanisms and therapeutic options].

PMID- 16110421
TI  - [The tuberculosis care institutions of the Landesversicherungsanstalt Berlin in
      Beelitz (1898 - 1998)].

PMID- 16110422
TI  - [INSPIRE: Multinational study on the effectivity of interferon-gamma1b in
      idiopathic fibrosis of the lung].

PMID- 16110423
TI  - Plasticity and reorganization of the uninjured brain.
AB  - Brain capacity is dependent not so much on the number of neurons but on the
      number of synaptic connections with functional connections that develop over a
      lifetime of genetic programming and life experiences. In the uninjured human
      brain, cortical reorganization that occurs in response to learning and experience
      is referred to as brain plasticity. Motor learning and complex environments
      result in a greater number of synapses and an increase in dendritic branching,
      whereas repetitive movements alone, in the absence of motor learning, do not.
      Learning and experience lead to an expansion of cortical representation, while
      failure to maintain training results in a contraction of cortical representation.
      In animals, loss of sensory peripheral afferent input results in an expansion of
      the forelimb representation of the intact adjacent cortex. Prolonged periods of
      peripheral nerve stimulation in both animals and humans can lead to
      reorganization of related sensorimotor cortical maps.

PMID- 16110424
TI  - Plasticity and reorganization of the brain post stroke.
AB  - Reorganization of the cortex post stroke is dependent not only on the lesion site
      but also on remote brain areas that have structural connections with the area
      damaged by the stroke. Motor recovery is largely dependent on the intact cortex
      adjacent to the infarct, which points out the importance of preserving the
      penumbral areas. There appears to be a priority setting with contralateral and
      ipsilateral motor pathways, with ipsilateral (unaffected hemisphere) pathways
      only becoming prominent after more severe strokes where functional contralateral
      (affected hemisphere) pathways are unable to recover. Ipsilateral or unaffected
      hemisphere motor pathway activation is therefore associated with a worse
      prognosis.

PMID- 16110425
TI  - Intrinsic factors influencing post stroke brain reorganization.
AB  - Reorganization of the brain, specifically the motor cortex surrounding the
      stroke, accounts for much of the observed neurological recovery following stroke.
      Not surprisingly, size of the stroke lesion has the greatest impact on
      neurological recovery in both animal and clinical research studies. Spontaneous
      recovery of lost function is possible after a cortical lesion, particularly if
      the lesion is small. Age correlates negatively with recovery; older individuals
      generally demonstrate slower and less complete recovery. However, age by itself
      is a poor predictor of functional recovery.

PMID- 16110426
TI  - Training and stimulation in post stroke recovery brain reorganization.
AB  - In both animal and clinical studies, training or rehabilitation increases
      cortical representation with subsequent functional recovery, whereas a lack of
      rehabilitation or training decreases cortical representation and delays recovery.
      Animals exposed to enriched environments post stroke have improved functional
      outcomes compared with animals exposed to nonenriched environments. In humans,
      stroke units may be the closest approximation there is to an enriched
      environment. However, studies indicate that patients spend the majority of time
      being inactive and alone while on a stroke unit. Given the animal evidence (which
      emphasizes increased stimulation and increased activity), there is clearly an
      opportunity for improving the stroke rehabilitation experience to maximize post
      stroke recovery.

PMID- 16110427
TI  - The role of timing and intensity of rehabilitation therapies.
AB  - In both animal and clinical studies, motor rehabilitation and training increase
      cortical representation and improve recovery, whereas lack of training decreases
      cortical representation for particular motor functions. In animals, delays in
      providing rehabilitation reduce the impact of therapy with a worsening in motor
      outcomes and a corresponding reduction in cortical reorganization. In clinical
      studies, there is an association between earlier admission to rehabilitation and
      better outcomes that correlates with animal work both in terms of functional
      gains from chronic stroke deficits and cortical reorganization. There is a likely
      relationship between therapy intensity and improvements in functional outcomes.
      Clinically, greater intensity of stroke rehabilitation has been associated with
      improved outcomes.

PMID- 16110428
TI  - The role of task-specific training in rehabilitation therapies.
AB  - Task-oriented therapy is important. It makes intuitive sense that the best way to
      relearn a given task is to train specifically for that task. In animals,
      functional reorganization is greater for tasks that are meaningful to the animal.
      Repetition alone, without usefulness or meaning in terms of function, is not
      enough to produce increased motor cortical representations. In humans, less
      intense but task-specific training regimens with the more affected limb can
      produce cortical reorganization and associated, meaningful functional
      improvements.

PMID- 16110429
TI  - Urinary incontinence after stroke: does rehabilitation make a difference? A
      systematic review of the effectiveness of behavioral therapy.
AB  - This study uses a comprehensive review of the literature to assess the scientific
      evidence for the effectiveness of behavioral therapies to treat urinary
      incontinence (UI) post stroke. Evidence for the different behavioral therapies
      was critically appraised to achieve a level of evidence based on Foley's
      classification of levels of evidence. Only four randomized clinical trials
      (RCTs), one cohort study, and recommendations from three clinical practice
      guidelines were found. There is limited evidence that bladder retraining with
      urge suppression in combination with pelvic floor exercises results in reduction
      of UI in male individuals with stroke. Further research is urgently needed to
      elucidate clinical recommendations about the efficacy of behavioral approaches.

PMID- 16110430
TI  - Funding, ethics, and assistive technology: should medical necessity be the
      criterion by which wheeled mobility equipment is justified?
AB  - The article will explore the use of the term medical necessity as it relates to
      wheeled mobility. Health insurance will cover a wheelchair if it is determined
      that it is medically necessary for a particular client. There are many different
      types of health insurance, and no universal definition of medical necessity. This
      presents a problem for clients and for individuals who are making wheelchair
      recommendations for clients. Case studies describe how equipment is currently
      recommended based on the limitations of the client's insurance coverage. As more
      equipment becomes available to improve the quality of life for people with
      disabilities, it will become harder for therapists recommending equipment to
      determine the limits of medical necessity.

PMID- 16110431
TI  - Stories of the silent: advocating for a disabled woman at end of life.
AB  - Carol's story is one of a disabled woman who, after living in her home for 10
      years with the assistance of paid providers, is hospitalized in an acute care
      facility for surgery. Postoperative delirium and confusion cause Carol to lose
      decision-making capacity for a short time; even when her mental clarity returns,
      Carol is subject to disability bias, possibly unconscious, by health care
      providers who are persuaded to listen to her psychiatrically impaired son. The
      case study demonstrates that patients with disabilities in the acute care
      hospital environment need health care providers and ethics consultants who are
      open to learning their story and incorporate their wishes into a plan of care
      that supports their dignity.

PMID- 16110434
TI  - Optimization of a multiplex minisequencing protocol for population studies and
      medical genetics.
AB  - Several technologically sophisticated high-throughput techniques have been
      recently developed for the study of human single nucleotide polymorphisms and the
      diagnosis of point mutations in human diseases. However, there is also a need for
      simple and inexpensive techniques suitable for clinical services and small
      research laboratories. Minisequencing meets the latter requirements. It is
      simple, non-radioactive and can be easily multiplexed by adding oligonucleotide
      tails of increasing size to the sequencing oligonucleotide primers. To optimize
      the minisequencing protocol, we designed a test multiplex system capable of
      typing simultaneously 12 different human autosomal single nucleotide
      polymorphisms. We discovered that the quality of minisequencing primers and the
      careful selection of the tail sequences were especially critical for success.
      This optimized protocol permits rapid genotyping at low cost and can serve as a
      blueprint for the creation of multiplex minisequencing systems suitable to
      virtually any typing application in population studies and medical genetics.

PMID- 16110435
TI  - Construction of a human Fab phage display library from antibody repertoires of
      osteosarcoma patients.
AB  - Osteosarcoma is the commonest type of primary malignant bone tumor, frequently
      found in adolescents at sites of rapid bone growth. Despite current management
      protocols, up to half of the patients succumb to this disease. Moreover, there is
      no well-characterized molecular marker for diagnosis and prognosis. Since phage
      display methodology allows the selection of human antibody fragments with
      potential use in clinical applications, we applied this procedure to construct a
      recombinant Fab (antigen binding fragment) library from patients with
      osteosarcoma. We used peripheral blood lymphocyte total RNA from 11 osteosarcoma
      patients and cloned recombinant Fab representing the micro, gamma and kappa chain
      antibody repertoires of these individuals. The resulting library was cloned in
      the pComb3X vector and attained 1.45 x 10(8) different functional forms. BstO I
      fingerprinting and DNA sequencing analysis of randomly selected clones revealed
      the diversity of the library, demonstrating that Fab harbors Vkappa chains from
      subgroups I to V, biased towards the A27 fragment, as normally reported for the
      human repertoire. Analysis of the VH repertoire revealed that our library has a
      slight bias towards the VH4 family, instead of the usually reported VH3. This is
      the first description of a phage display library from osteosarcoma patients. We
      believe these human Fab fragments will provide a valuable tool for the study of
      this neoplasia and could also contribute to improvements in the diagnosis of this
      disease.

PMID- 16110436
TI  - Uses and limitations of two molecular cytogenetic techniques for the study of
      arrested embryos obtained through assisted reproduction technology.
AB  - We studied chromosomal abnormalities in arrested embryos produced by assisted
      reproductive technology with fluorescence in situ hybridization (FISH) and
      comparative genomic hybridization (CGH) in order to determine the best technique
      for evaluating chromosomal aneusomies to be implemented in different situations.
      We examined individual blastomeres from arrested embryos by FISH and arrested
      whole embryos by CGH. All of the 10 FISH-analyzed embryos gave results, while
      only 7 of the 30 embryos analyzed by CGH were usable. Fifteen of the 17 embryos
      were chromosomally abnormal. CGH provided more accurate data for arrested
      embryos; however, FISH is the technique of choice for screening in
      preimplantation genetic diagnosis, because the results can be obtained within a
      day, while the embryos are still in culture.

PMID- 16110437
TI  - Genetics of efficient feed utilization and national cattle evaluation: a review.
AB  - Selection for the wide range of traits for which most beef breed associations
      calculate expected progeny differences focus on increasing the outputs of the
      production system, thereby increasing the genetic potential of cattle for
      reproductive rates, weights, growth rates, and end-product yield. Feed costs,
      however, represent a large proportion of the variable cost of beef production and
      genetic improvement programs for reducing input costs should include traits
      related to feed utilization. Feed conversion ratio, defined as feed inputs per
      unit output, is a traditional measure of efficiency that has significant
      phenotypic and genetic correlations with feed intake, growth rate, and mature
      size. One limitation is that favorable decreases in feed to gain either directly
      or due to correlated response to increasing growth rate do not necessarily relate
      to improvement in efficiency of feed utilization. Residual feed intake is defined
      as the difference between actual feed intake and that predicted on the basis of
      requirements for maintenance of body weight and production. Phenotypic
      independence of residual feed intake with growth rate, body weight, and other
      energy depots can be forced. However, genetic associations may remain when a
      phenotypic prediction approach is used. Heritability estimates for phenotypic
      residual feed intake have been moderate, ranging from 0.26 to 0.43. Genetic
      correlations of phenotypic residual feed intake with feed intake have been large
      and positive, suggesting that improvement would produce a correlated response of
      decreased feed intake. Residual feed intake estimated by genetic regression
      results in a zero genetic correlation with its predictors, which reduces concerns
      over long-term antagonistic responses such as increased mature size and
      maintenance requirements. The genetic regression approach requires knowledge of
      genetic covariances of feed intake with weight and production traits. Cost of
      individual feed intake measurements on potential replacements must be considered
      in implementation of national cattle evaluations for efficiency of feed
      utilization. These costs need to be compared to expected, and, if possible,
      realized rates of genetic change and the associated reduction in feed input
      requirements.

PMID- 16110438
TI  - The mutation G298A-->Ala100Thr on the coding sequence of the Duffy
      antigen/chemokine receptor gene in non-caucasian Brazilians.
AB  - Ala100Thr has been suggested to be a Caucasian genetic marker on the FY*B allele.
      As the Brazilian population has arisen from miscegenation among Portuguese,
      Africans, and Indians, this mutation could possibly be found in Euro- and Afro
      Brazilians, or in Brazilian Indians. Fifty-three related individuals and a random
      sample of 100 subjects from the Brazilian population were investigated using the
      polymerase chain reaction and four restriction fragment length polymorphisms.
      Confirming the working hypothesis, among the related individuals three Afro
      Brazilians (two of them a mother and daughter) and a woman of Amerindian descent
      had the Ala100Thr mutation on the FY*B allele. Five non-related Euro-Brazilians
      also carried the mutation. All nine individuals presented the Fy(a-b+) phenotype.
      We conclude that the Ala100Thr mutation can occur in populations other than
      Caucasians and that this mutation does not affect Duffy expression on red blood
      cells. Gene frequencies for this allele in the non-related individuals were in
      agreement with those of other populations. The Duffy frequencies of two
      Amerindian tribes were also investigated.

PMID- 16110439
TI  - Transgene elimination in genetically modified dry bean and soybean lines.
AB  - Transgene elimination is a poorly studied phenomenon in plants. We made genetic
      and molecular studies of a transgenic dry bean line immune to bean golden mosaic
      geminivirus and a soybean line. In both lines, the transgenes were stable during
      the vegetative phase but were eliminated during meiosis. Due to its potential
      biotechnological value, this transgenic line was micropropagated by grafting and
      the vegetative copies were studied for more than two years. More than 300 plants
      of progeny were obtained during this period, demonstrating that the phenomenon of
      elimination was consistently repeated and offering an opportunity for detailed
      study of transgene elimination, including the characterization of the integration
      sites. Cloning and sequencing of the transgenic loci, reciprocal crosses to
      untransformed plants, genomic DNA blots, and GUS assays were performed in the
      transgenic lines. Based on the molecular and genetic characterization, possible
      mechanisms involved in transgene elimination include intrachromosomal
      recombination, genetic instability resulting from the tissue culture
      manipulations, and co-elimination of transgenes, triggered by a process of genome
      defense.

PMID- 16110440
TI  - Effectiveness of liposomes to transfect livestock fibroblasts.
AB  - The development of an efficient transfection system in livestock cells is an
      important step towards investigating gene transfer and the functioning and
      production of transgenic animals. Important factors involved in cationic liposome
      mediated gene transfer were evaluated through in vitro transfection of bovine,
      caprine and ovine fibroblast cells. Transfection of plasmid DNA complexes of
      different commercially available liposomes (Lipofectamine, Lipofectin, Cellfectin
      and DMRIE-C; Gibco-BRL, USA) was evaluated utilizing the following parameters:
      DNA/liposome ratio, cell density, DNA conformation, and the effect of
      transfection time on the efficiency of bovine fibroblasts to express a reporter
      gene. The effects and concentrations of liposomes were also evaluated in caprine
      and ovine fibroblasts. Lipofectamine alone and Lipofectamine with Plus reagent
      induced high-frequency expression of beta-galactosidase and neo genes in all
      cells evaluated (47 and 88.3%, respectively). Regarding phenotype, chromosomal
      stability was similar in transfected and non-transfected cells. The parameters
      set in this study will establish a foundation for utilizing transfected
      fibroblast cells to generate transgenic animals through nuclear transfer
      technology and gene function studies.

PMID- 16110441
TI  - Genetic variation and population structure of two species of neo-tropical mud
      mussels (Mytella spp).
AB  - Mytella guyanensis Lamarck (1819) and Mytella charruana d'Orbigny (1846) are
      widespread euryhaline bivalves that have become commercially important in Brazil.
      Despite their importance, however, no genetic information that would be useful to
      orient governmental policies is available for these species. We analyzed, through
      allozyme electrophoresis, populations of M. guyanensis and M. charruana along
      3,500 km of Brazilian coast. Pairwise comparisons among gene frequencies in M.
      guyanensis resulted in high levels of pairwise gene identity (I = 0.976 to
      0.998). Conversely, significant levels of population structure were found in both
      M. guyanensis (FST = 0.089) and M. charruana (FST = 0.102). Heterozygosity levels
      for both species were high (H(e) = 0.090 to 0.134 in M. guyanensis and H(e) =
      0.191 to 0.228 in M. charruana). The larger population size of M. charruana could
      explain, at least partially, the higher levels of genetic variability for this
      species. These levels of genetic variability yield an effective population size
      estimate of about 300,000 for M. guyanensis, and 540,000 for M. charruana, based
      on neutralist expectations. Remarkably, these numbers are much smaller than the
      estimated actual population sizes. This distortion might be explained by unstable
      population sizes and it suggests that long-term genetic variability studies are
      crucial to prevent artifactual viability analysis data for these commercially
      exploited species.

PMID- 16110442
TI  - Bioinformatics of the Paracoccidioides brasiliensis EST Project.
AB  - Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis,
      an endemic mycosis of Latin America. This fungus presents a dimorphic character;
      it grows as a mycelium at room temperature, but it is isolated as yeast from
      infected individuals. It is believed that the transition from mycelium to yeast
      is important for the infective process. The Functional and Differential Genome of
      Paracoccidioides brasiliensis Project--PbGenome Project was developed to study
      the infection process by analyzing expressed sequence tags--ESTs, isolated from
      both mycelial and yeast forms. The PbGenome Project was executed by a consortium
      that included 70 researchers (professors and students) from two sequencing
      laboratories of the midwest region of Brazil; this project produced 25,741 ESTs,
      19,718 of which with sufficient quality to be analyzed. We describe the
      computational procedures used to receive process, analyze these ESTs, and help
      with their functional annotations; we also detail the services that were used for
      sequence data exploration. Various programs were compared for filtering and
      grouping the sequences, and they were adapted to a user-friendly interface. This
      system made the analysis of the differential transcriptome of P. brasiliensis
      possible.

PMID- 16110443
TI  - Cell signaling pathways in Paracoccidioides brasiliensis--inferred from
      comparisons with other fungi.
AB  - The human fungal pathogen Paracoccidioides brasiliensis is an ascomycete that
      displays a temperature-dependent dimorphic transition, appearing as a mycelium at
      22 degrees C and as a yeast at 37 degrees C, this latter being the virulent form.
      We report on the in silico search made of the P. brasiliensis transcriptome
      expressed sequence tag database for components of signaling pathways previously
      known to be involved in morphogenesis and virulence in other species of fungi,
      including Saccharomyces cerevisiae, Cryptococcus neoformans, Candida albicans,
      and Aspergillus fumigatus. Using this approach, it was possible to identify
      several protein cascades in P. brasiliensis, such as i) mitogen-activated protein
      kinase signaling for cell integrity, cell wall construction, pheromone/mating,
      and osmo-regulation, ii) the cAMP/PKA system, which regulates fungal development
      and virulence, iii) the Ras protein, which allows cross-talking between cascades,
      iv) calcium-calmodulin-calcineurin, which controls cell survival under oxidative
      stress, high temperature, and membrane/cell wall perturbation, and v) the target
      of rapamycin pathway, controlling cell growth and proliferation. The ways in
      which P. brasiliensis responds to the environment and modulates the expression of
      genes required for its survival and virulence can be inferred through comparison
      with other fungi for which this type of data is already available.

PMID- 16110444
TI  - Cell cycle, DNA replication, repair, and recombination in the dimorphic human
      pathogenic fungus Paracoccidioides brasiliensis.
AB  - DNA replication, together with repair mechanisms and cell cycle control, are the
      most important cellular processes necessary to maintain correct transfer of
      genetic information to the progeny. These processes are well conserved throughout
      the Eukarya, and the genes that are involved provide essential information for
      understanding the life cycle of an organism. We used computational tools for data
      mining of genes involved in these processes in the pathogenic fungus
      Paracoccidiodes brasiliensis. Data derived from transcriptome analysis revealed
      that the cell cycle of this fungus, as well as DNA replication and repair, and
      the recombination machineries, are highly similar to those of the yeast
      Saccharomyces cerevisiae. Among orthologs detected in both species, there are
      genes related to cytoskeleton structure and assembly, chromosome segregation, and
      cell cycle control genes. We identified at least one representative gene from
      each step of the initiation of DNA replication. Major players in the process of
      DNA damage and repair were also identified.

PMID- 16110445
TI  - Paracoccidioides brasiliensis RNA biogenesis apparatus revealed by functional
      genome analysis.
AB  - The RNA biogenesis machinery of Paracoccidioides brasiliensis was assessed by
      comparative analyses of PbAESTs (P. brasiliensis assembled expressed sequence
      tags (ESTs)) with sequences from Saccharomyces cerevisiae MIPS database. PbAESTs
      related to almost all categories of S. cerevisiae RNA biogenesis were found. Two
      of the 12 S. cerevisiae RNA Pol II core subunits, Rpb3 and Rpb7, were found,
      probably reflecting the growth phase from which the cDNA libraries used in ESTs
      generation were constructed, as well as the low abundance of some of these
      transcripts. We have also found orthologs to TATA-box-binding protein (TBP), and
      at least one subunit of each TBP-associated factors (TFII) in P. brasiliensis
      transcriptome, except TFIIB. Genes associated to the chromatin remodeling
      complex, as well as transcription factors probably involved in the control of
      genes associated to a sexual cycle and virulence, were also identified. With
      respect to the pre-mRNA processing, 65 PbAEST orthologs to S. cerevisiae basal
      splicing machinery and 21 orthologs of 5'- and 3'-end formation processes were
      found. Components involved in RNA interference were detected, suggesting that
      this gene expression regulation mechanism is probably used by P. brasiliensis.
      Twelve PbAESTs related to Pol I and Pol III machineries were assigned as S.
      cerevisiae orthologs. Finally, 25 and 10 PbAESTs associated to rRNA and tRNA
      processing, respectively, were detected. Taken together, our results enable us to
      depict, for the first time, a global view of transcription and RNA processing in
      P. brasiliensis.

PMID- 16110446
TI  - Paracoccidioides brasiliensis translation and protein fate machineries revealed
      by functional genome analysis.
AB  - The translational and post-translational modification machineries of
      Paracoccidioides brasiliensis were assessed by means of comparative analyses of
      PbAESTs (P. brasiliensis assembled expressed sequence tags) with sequences
      deposited on different databases. Of the 79 sequences corresponding to cytosolic
      ribosomal proteins, we were able to find 78 in the P. brasiliensis transcriptome.
      Nineteen of the 27 Saccharomyces cerevisiae genes related to translation
      initiation were also found. All eukaryotic elongation factors were detected in P.
      brasiliensis transcriptome, with eEF1A as one of the most expressed genes.
      Translation termination is performed, in eukaryotes, by factors 1 and 3 (eRF1,
      eRF3). In P. brasiliensis transcriptome it was possible to identify eRF3, but not
      eRF1. Sixteen PbAESTs showing aminoacyl-tRNA synthetase-predicted activities were
      found in our analyses, but no cysteinyl-, leucyl-, asparagyl- and arginyl-tRNA
      synthetases were detected. Among the mitochondrial ribosomal proteins, we have
      found 20 and 18 orthologs to S. cerevisiae large and small ribosomal subunit
      proteins, respectively. We have also found three PbAESTs similar to Neurospora
      crassa mitochondrial ribosomal genes, with no similarity with S. cerevisiae
      genes. Although orthologs to S. cerevisiae mitochondrial EF-Tu, EF-G and RF1 have
      been found in P. brasiliensis transcriptome, no sequences corresponding to
      functional EF-Ts were detected. In addition, 64 and 28 PbAESTs associated to
      protein modification and degradation, respectively, were found. These results
      suggest that these machineries are well conserved in P. brasiliensis, when
      compared to other organisms.

PMID- 16110447
TI  - General metabolism of the dimorphic and pathogenic fungus Paracoccidioides
      brasiliensis.
AB  - Annotation of the transcriptome of the dimorphic fungus Paracoccidioides
      brasiliensis has set the grounds for a global understanding of its metabolism in
      both mycelium and yeast forms. This fungus is able to use the main carbohydrate
      sources, including starch, and it can store reduced carbons in the form of
      glycogen and trehalose; these provide energy reserves that are relevant for
      metabolic adaptation, protection against stress and infectivity mechanisms. The
      glyoxylate cycle, which is also involved in pathogenicity, is present in this
      fungus. Classical pathways of lipid biosynthesis and degradation, including those
      of ketone body and sterol production, are well represented in the database of P.
      brasiliensis. It is able to synthesize de novo all nucleotides and amino acids,
      with the sole exception of asparagine, which was confirmed by the fungus growth
      in minimal medium. Sulfur metabolism, as well as the accessory synthetic pathways
      of vitamins and co-factors, are likely to exist in this fungus.

PMID- 16110448
TI  - The cell wall of Paracoccidioides brasiliensis: insights from its transcriptome.
AB  - The cell wall of a human pathogenic fungus is in contact with the host, serves as
      a barrier against host defense mechanisms and harbors most fungal antigens. In
      addition, cell wall biosynthesis pathways have been recognized as essential to
      viability and as specific drug targets. Paracoccidioides brasiliensis is a
      dimorphic fungus that presents mycelium morphology in the free environment and
      causes infection in a yeast form. The morphogenetic conversion is correlated with
      changes in the cell wall composition, organization and structure. Based on
      transcriptome analysis, the enzymes involved in the biosynthesis and remodeling
      of cell wall polysaccharides, as well as several cell wall-associated molecules
      of P. brasiliensis, were identified and addressed in further detail.

PMID- 16110449
TI  - Screening for glycosylphosphatidylinositol-anchored proteins in the
      Paracoccidioides brasiliensis transcriptome.
AB  - Open reading frames in the transcriptome of Paracoccidioides brasiliensis were
      screened for potential glycosylphosphatidylinositol (GPI)-anchored proteins,
      which are a functionally and structurally diverse family of post-translationally
      modified molecules found in a variety of eukaryotic cells. Numerous studies have
      demonstrated that various GPI anchor sequences can affect the localization of
      these proteins in the plasma membrane or the cell wall. The GPI anchor core is
      produced in the endoplasmic reticulum by sequential addition of monosaccharides
      and phospho-ethanolamine to phosphatidylinositol. The complete GPI anchor is post
      translationally attached to the protein carboxyl-terminus by GPI transamidases.
      Removal of this GPI lipid moiety by phospholipases generates a soluble form of
      the protein. The identification of putative GPI-attached proteins in the P.
      brasiliensis transcriptome was based on the following criteria: the presence of
      an N-terminal signal peptide for secretion and a hydrophobic region in the C
      terminus presenting the GPI-attachment site. The proteins that were identified
      were in several functional categories: i) eight proteins were predicted to be
      enzymes (Gel1, Gel2, Gel3, alpha-amylase, aspartic proteinase, Cu-Zn SOD, DFG5,
      PLB); ii) Ag2/PRA, ELI-Ag1 and Gel1 are probably surface antigens; iii) Crh-like
      and the GPI-anchored cell wall protein have a putative structural role; iv) ECM33
      and Gels (1, 2 and 3) are possibly involved in cell wall biosynthesis, and v)
      extracellular matrix protein is considered to be an adhesion protein. In
      addition, eight deduced proteins were predicted to localize in the plasma
      membrane and six in the cell wall. We also identified proteins involved in the
      synthesis, attachment and cleaving of the GPI anchor in the P. brasiliensis
      transcriptome.

PMID- 16110450
TI  - Molecular chaperones in the Paracoccidioides brasiliensis transcriptome.
AB  - Paracoccidioides brasiliensis is a thermally dimorphic and a human pathogenic
      fungus. Our group has partially sequenced its transcriptome and generated a
      database of mycelial and yeast PbAESTs (P. brasiliensis assembled expressed
      sequence tags). In the present review we describe the identification of PbAESTs
      encoding molecular chaperones. These proteins, involved in protein folding and
      renaturation, are also implicated in several other biological processes, where
      the dimorphic transition is of particular interest. Another important issue
      concerning these proteins refers to their participation in the
      immunopathogenicity of infectious diseases. We have found 438 ESTs (184 in
      mycelium and 253 in yeast) encoding P. brasiliensis molecular chaperones and
      their co-chaperones, which were clustered in 48 genes. These genes were
      classified in families, corresponding to three small chaperones, nine HSP40s, 10
      HSP60s, seven HSP70s, five HSP90s, four HSP100s, and 10 other chaperones. These
      results greatly increase the knowledge on P. brasiliensis molecular chaperones,
      since only eight of such proteins had been previously characterized.

PMID- 16110451
TI  - Transcriptome overview of Paracoccidioides brasiliensis proteases.
AB  - Proteases perform a wide variety of functions inside and outside cells,
      regulating many biological processes. Infectious microorganisms use proteases,
      either secreted or attached to their cell surface to weaken and invade their
      hosts. Therefore, proteases are targets for drugs against a diverse set of
      diseases. Paracoccidioides brasiliensis is the most prevalent fungal pathogen
      causing systemic mycosis in Latin America. The development of
      paracoccidioidomycosis depends on interactions between fungal and host components
      and proteases have been described as important factors implicated in the
      mechanism of host colonization by fungi. The primary goal for this study is to
      present an overview of the transcriptome sequences--identified cDNAs that encode
      proteases. We obtained a total of 53 cDNAs encoding proteases; 15 were classified
      as ATP-independent, 12 as ATP-dependent, 22 as proteasome subunits, and 4 as
      deubiquitinating proteases. The mechanisms and biological activity of these
      proteases differ in substrate specificity and in catalytic mechanisms.

PMID- 16110452
TI  - Virulence insights from the Paracoccidioides brasiliensis transcriptome.
AB  - Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis, is
      a dimorphic fungus, which is found as mycelia at 22-26 degrees C and as yeasts at
      37 degrees C. A remarkable feature common to several pathogenic fungi is their
      ability to differentiate from mycelium to yeast morphologies, or vice-versa.
      Although P. brasiliensis is a recognized pathogen for humans, little is known
      about its virulence genes. In this sense, we performed a search for putative
      virulence genes in the P. brasiliensis transcriptome. BLAST comparative analyses
      were done among P. brasilienses assembled expressed sequence tags (PbAESTs) and
      the sequences deposited in GenBank. As a result, the putative virulence PbAESTs
      were grouped into five classes, metabolism-, cell wall-, detoxification-related,
      secreted factors, and other determinants. Among these, we have identified
      orthologs of the glyoxylate cycle enzymes, a metabolic pathway involved in the
      virulence of bacteria and fungi. Besides the previously described alpha- and beta
      glucan synthases, orthologs to chitin synthase and mannosyl transferases, also
      important in cell wall synthesis and stabilization, were identified. With respect
      to the enzymes involved in the intracellular survival of P. brasiliensis,
      orthologs to superoxide dismutase, thiol peroxidase and an alternative oxidase
      were also found. Among the secreted factors, we were able to find phospholipase
      and urease orthologs in P. brasiliensis transcriptome. Collectively, our results
      suggest that this organism may possess a vast arsenal of putative virulence
      genes, allowing the survival in the different host environments.

PMID- 16110453
TI  - Transporters in the Paracoccidioides brasiliensis transcriptome: insights on drug
      resistance.
AB  - In the struggle for life, the capacity of microorganisms to synthesize and
      secrete toxic compounds (inhibiting competitors) plays an important role in
      successful survival of these species. This ability must come together with the
      capability of being unaffected by these same compounds. Several mechanisms are
      thought to avoid the toxic effects. One of them is toxin extrusion from the
      intracellular environment to the outside vicinity, using special transmembrane
      proteins, referred to as transporters. These proteins are also important for
      other reasons, since most of them are involved in nutrient uptake and cellular
      excretion. In cancer cells and in pathogens, and particularly in fungi, some of
      these proteins have been pointed out as responsible for an important phenotype
      known as multidrug resistance (MDR). In the present study, we tried to identify
      in the Paracoccidioides brasiliensis transcriptome, transporter-ortholog genes
      from the two major classes: ATP binding cassette and major facilitator
      superfamily transporter. We found 22 groups with good similarity with other
      fungal ATP binding cassette transporters, and four Paracoccidioides brasilienses
      assembled expressed sequence tags that probably code for major facilitator
      superfamily proteins. We also focused on fungicide resistance orthologs already
      characterized in other pathogenic fungi. We were able to find homologs to C.
      albicans CDR1, CDR2, and MDR1, Saccharomyces cerevisiae PDR5 and Aspergillus AtrF
      genes, all of them related to azole resistance. As current treatment for
      paracoccidioidomycosis mainly uses azole derivatives, the presence of these genes
      can be postulated to play a similar role in P. brasiliensis, warning us for the
      possibility of resistant isolate emergence.

PMID- 16110454
TI  - Oxidative stress response in Paracoccidioides brasiliensis.
AB  - Survival of pathogenic fungi inside human hosts depends on evasion from the host
      immune system and adaptation to the host environment. Among different insults
      that Paracoccidioides brasiliensis has to handle are reactive oxygen and nitrogen
      species produced by the human host cells, and by its own metabolism. Knowing how
      the parasite deals with reactive species is important to understand how it
      establishes infection and survives within humans. The initiative to describe the
      P. brasiliensis transcriptome fostered new approaches to study oxidative stress
      response in this organism. By examining genes related to oxidative stress
      response, one can evaluate the parasite's ability to face this condition and
      infer about possible ways to overcome this ability. We report the results of a
      search of the P. brasiliensis assembled expressed sequence tag database for
      homologous sequences involved in oxidative stress response. We described several
      genes coding proteins involved in antioxidant defense, for example, catalase and
      superoxide dismutase isoenzymes, peroxiredoxin, cytochrome c peroxidase,
      glutathione synthesis enzymes, thioredoxin, and the transcription factors Yap1
      and Skn7. The transcriptome analysis of P. brasiliensis reveals a pathogen that
      has many resources to combat reactive species. Besides characterizing the
      antioxidant defense system in P. brasiliensis, we also compared the ways in which
      different fungi respond to oxidative damage, and we identified the basic features
      of this response.

PMID- 16110455
TI  - Therapeutic targets in Paracoccidioides brasiliensis: post-transcriptome
      perspectives.
AB  - The rise in antifungal resistance, observed as a result of the increasing numbers
      of immunocompromised patients, has made the discovery of new targets for drug
      therapy imperative. The description of the Paracoccidioides brasiliensis
      transcriptome has allowed us to find alternatives to refine current therapy
      against paracoccidioidomycosis. We used comparative analysis of expressed
      sequence tags to find promising drug targets that have been addressed in other
      pathogens. We divided the analysis into six different categories, based on the
      involvement of the targeted mechanisms in the cell: i) cell wall construction,
      ii) plasma membrane composition, iii) cellular machinery, iv) cellular
      metabolism, v) signaling pathways, and vi) other essential processes. Through
      this approach, it has been possible to infer strategies to develop alternative
      drugs against this pathogen.

PMID- 16110456
TI  - Hydrolytic enzymes in Paracoccidioides brasiliensis--ecological aspects.
AB  - Paracoccidioides brasiliensis is a thermally dimorphic fungus that causes
      paracoccidioidomycosis. The yeast form of this pathogen is found in the animal
      host whereas the mycelial form is recovered from living and non-living organic
      material. The sole carbon source available in these habitats is represented by
      polysaccharides from the plant cell wall. Hydrolytic enzymes are necessary to
      convert these polymers into simple sugars for fungal metabolism. We report on the
      presence of ortholog genes of hydrolytic enzymes identified in the P.
      brasiliensis transcriptome and on hydrolytic activities in supernatants of
      induced P. brasiliensis cultures of mycelium and yeast cells. Enzymatic assays
      have shown cellulase and xylanase activities, both being higher in mycelium than
      in the yeast form. Amylase and chitinase activities were detected only in
      mycelium. Data so far reinforce the idea that mycelial P. brasiliensis is a
      saprobe.

PMID- 16110457
TI  - Impaired expression of acyl-CoA synthetase 5 in sporadic colorectal
      adenocarcinomas.
AB  - Several pathways of fatty acid metabolism have been shown to be associated with
      the pathogenesis of colorectal cancer. Fatty acid acyl-CoA thioesters are formed
      from free fatty acids and coenzyme A by the activity of acyl-CoA synthetases
      (ACSs). Whilst an increase in ACS4 expression has been associated with colorectal
      carcinogenesis, little is known about possible pathogenetic functions of other
      ACS isoforms, such as ACS5, in tumourigenesis. In the present study, gene
      expression, protein synthesis, and enzymatic activity of ACS5 in sporadic
      colorectal adenocarcinomas, adenomas, and established cell lines were analysed
      using RT-PCR, western blot analysis, immunofluorescence, and an enzymatic assay.
      Enhanced expression of ACS5 mRNA and protein as well as enzymatic activity was
      found in adenomas and in 11 (73%; group 1) of 15 colorectal adenocarcinomas
      investigated, while a decrease of ACS5 was seen in four tumours (27%; group 2).
      However, basal ACS5 enzymatic activity was increased as a percentage of the total
      activity of ACSs in both groups, arguing for an absolute (group 1) or relative
      (group 2) increase in ACS5 enzymatic activity in all adenocarcinomas
      investigated. These findings are reflected by in vitro analysis of three
      established colorectal adenocarcinoma cell lines, in which activity of ACS5
      occurred. The results suggest the involvement of ACS5 in the early genesis of
      colorectal cancer, most likely by modification of the transport and pool
      formation of long-chain acyl-CoA thioesters, as recently demonstrated for other
      isoforms of the ACS family.

PMID- 16110458
TI  - Critical overexpression of thrombospondin 1 in chronic leg ischaemia.
AB  - The aim of this study was to identify gene expression governing the balance of
      angiogenic and angiostatic factors in human ischaemic leg tissues. In situ
      hybridization was used to screen for the expression of angiogenesis-related genes
      in tissues from 13 amputated limbs from patients suffering from critical leg
      ischaemia. The authors tested for mRNA of hypoxia-inducible transcription factors
      1 alpha and 2 alpha, vascular endothelial growth factor, and its receptors VEGFR
      1 and -2, the angiopoietin receptor Tie2, and the anti-angiogenic molecule
      thrombospondin 1. The expression levels of the genes in proximal, healthy muscles
      were compared with those in the distal, ischaemic counterparts. Surprisingly,
      only thrombospondin 1 was overexpressed in the ischaemic part of the leg of all
      patients studied. Thrombospondin 1 mRNA was assayed by real-time RT-PCR and the
      gene was overexpressed 20-fold. The presence of its encoded protein was confirmed
      by western blotting. The overproduction of this anti-angiogenic molecule was
      associated with a decrease in capillary density in the affected muscles.
      Thrombospondin 1 is thus a marker of chronic ischaemia and may affect
      angiogenesis in ischaemic tissues.

PMID- 16110459
TI  - Type XIII collagen expression is induced during malignant transformation in
      various epithelial and mesenchymal tumours.
AB  - Little information is available on the expression of transmembrane type XIII
      collagen in human diseases. The present study has investigated the expression of
      this collagen in cancer, in particular during malignant transformation. By
      combining the tissue microarray technique with in situ hybridization, a
      consistent pattern of clearly increased type XIII collagen mRNA expression was
      found in the stromal compartment of epithelial tumours and throughout mesenchymal
      tumours. Slightly elevated mRNA expression was observed in dysplastic samples and
      in malignant epithelial cells. It is also demonstrated that factors secreted into
      the culture medium by tumour cells, in particular the growth factor TGF-beta,
      contribute to the induction of type XIII collagen expression, and trigger
      concomitantly a profound phenotypic and morphological transition of cultured
      primary fibroblasts. Reciprocally, type XIII collagen may alter the growth milieu
      of malignant cells as the soluble type XIII collagen ectodomain influenced the
      adherence and spreading of cells cultured on vitronectin-rich matrix. It is
      proposed that malignant transformation stimulates the expression of type XIII
      collagen, particularly in the tumour stroma and to a lesser extent in the
      epithelium, and that this high type XIII collagen expression may contribute to
      tumour progression and behaviour by modulating cell-matrix interactions.

PMID- 16110460
TI  - High-throughput capillary electrophoresis for the identification and
      differentiation of seven species of Eimeria from chickens.
AB  - A capillary electrophoretic approach has been evaluated for the identification of
      seven currently recognised species of Eimeria infecting chickens. The second
      internal transcribed spacer of ribosomal DNA is PCR-amplified from any of the
      seven species using a single set of oligonucleotide primers (one of which is
      fluorescently labelled). The amplicons are heat-denatured and subjected to
      capillary electrophoresis in a MegaBACE 1000 (Amersham). The chromatograms
      captured are stored electronically and then analysed using MegaBACE Fragment
      Profiler software. Using control DNA samples representing monospecific lines of
      Eimeria, specific peaks in the chromatograms were defined for the unequivocal
      identification of each of the seven species and their differentiation.
      Electrophoretic reading and analysis are carried out automatically, thus making
      it a time- and cost-effective method. This procedure should find applicability as
      a tool for the quality control of Eimeria vaccines, the monitoring of coccidiosis
      outbreaks and the high-throughput analysis of oocyst samples for epidemiological
      surveys.

PMID- 16110461
TI  - Capillary electrochromatography of therapeutic peptides on mixed-mode
      butylmethacrylate monoliths.
AB  - In this study, a porous mixed-mode n-alkyl methacrylate-based monolith has been
      used in the separation of therapeutic peptides. While the sulfonic acid (SCX)
      moiety derived from 2-acrylamido-2-methyl-1-propanesulfonic acid supports the
      generation of a stable electroosmotic flow (EOF) at both acidic and basic pH
      values, the butyl ligands provide the nonpolar sites for chromatographic
      resolution. The performance of the monolith was evaluated regarding the influence
      of pH on chromatographic resolution of peptides. The suitability of the
      butylmethacrylate/SCX monolith for the analysis of therapeutic peptides
      containing basic centres, for example arginine, at moderately high pH 9.5 and the
      stability to repeat injections of a mixture of peptides was demonstrated.
      Separations with efficiencies as high as 5.0 x 10(5) plates/m were obtained and
      the migration behaviour of the peptides at both low (2.8) and high (9.5) pH
      values could be rationalised based on their charge, molecular mass/shape and
      relative hydrophobicities.

PMID- 16110462
TI  - Cloud point preconcentration prior to capillary zone electrophoresis:
      simultaneous determination of platinum and palladium at trace levels.
AB  - The incorporation of a cloud point extraction (CPE) step prior to capillary
      electrophoresis (CE) for simultaneously determining platinum and palladium at sub
      microg/L levels is presented and evaluated. The analytes were extracted as 2-(5
      bromo-2-pyridylazo)-5-diethylaminophenol complexes, at pH 2.0, mediated by
      micelles of the nonionic surfactant polyethyleneglycolmono-p-nonylphenyl ether
      (PONPE 7.5). The separation-determination step was developed from 150 microL of
      the extracted surfactant-rich phase diluted with 50 microL of acetonitrile (ACN).
      An exhaustive study of the variables affecting the cloud point extraction with
      PONPE 7.5 and the CZE step was done. The type and composition of the background
      electrolytes (BGEs) were investigated with respect to separation selectivity,
      reproducibility, and stability. A BGE of 50 mM monobasic sodium phosphate
      containing 30% ACN, pH 4.53 was found to be optimal for the separation of metal
      chelates. Detection was performed at 576 nm. An enrichment factor of 250 was
      obtained for the preconcentration of 50 mL of sample solution. The detection
      limits for the preconcentration of 50 mL of sample were 0.04 microg/L for Pt and
      0.08 microg/L for Pd. As an analytical demonstration, ultratrace concentrations
      of platinum and palladium were conveniently quantitated in spiked water and urine
      samples.

PMID- 16110463
TI  - Artificial neural network prediction of retention factors of some benzene
      derivatives and heterocyclic compounds in micellar electrokinetic chromatography.
AB  - A 5-4-1 artificial neural network (ANN) was constructed and trained for
      prediction of the retention factors of some benzene derivatives and heterocyclic
      compounds in micellar electrokinetic chromatography (MEKC) based on quantitative
      structure-property relationship (QSPR). The inputs of this network are
      theoretically derived descriptors that were chosen by the stepwise variable
      selection techniques. These descriptors are: molecular surface area, maximum
      value of electron density on atom in molecule, path four connectivity index,
      average molecular weight, and sum of atomic polarizability which were selected by
      using stepwise multiple linear regression as a feature selection technique. The
      standard errors of training, test, and validation sets for the ANN model are
      0.091, 0.119, and 0.114, respectively. Results obtained showed that nonlinear
      model can simulate the relationship between the structural descriptors and the
      retention factors of the molecules in data set accurately. Also the appearance of
      these descriptors in QSPR models reveals the role of electronic and steric
      interactions in solute retention in MEKC.

PMID- 16110464
TI  - On-line sample enrichment for the determination of proteins by capillary zone
      electrophoresis with poly(vinyl alcohol)-coated bubble cell capillaries.
AB  - Field-amplified sample stacking (FASS) is used to separate basic proteins in a
      poly-(vinyl alcohol)-coated bubble cell capillary. To our knowledge, this is the
      first paper describing the on-column stacking of proteins (as cations) using FASS
      in bubble cell capillary. The bubble cell capillary is fabricated using a one
      step method. Cetyltrimethylammonium chloride is added into the running buffer to
      reverse the EOF and, thus, to pump the water plug out during the sample stacking
      step. The effect of the water plug lengths and sample injection durations were
      investigated and optimized. The results obtained were compared with those for the
      normal capillary without bubble cell in terms of resolution and sensitivity
      enhancement. Under the optimal condition, this method can improve the sensitivity
      of the peak areas ranging from 5000- to 26 000-fold. The RSDs (n = 5) of the
      migration time and peak area are satisfactory (less than 0.6 and 12%,
      respectively). Application of the capillary electrophoresis method with bubble
      cell, FASS, and UV detection thereby leads to the determination of these proteins
      at concentrations ranging from 3 to 10 ng/mL, based on a signal-to-noise ratio of
      3:1.

PMID- 16110465
TI  - Anomalous electrophoretic behavior of a very acidic protein: ribonuclease U2.
AB  - Ribonuclease U2 is a low-molecular-weight acidic protein with three disulfide
      bridges. This protein displays an anomalous electrophoretic behavior on standard
      SDS-PAGE. The electrophoretic mobility of the nonreduced protein roughly
      corresponds to its molecular mass while the migration of the reduced protein
      would be in accordance with the expected molecular mass of the protein dimer.
      This study reveals that the protein does not bind SDS under the SDS-PAGE
      conditions, its electrophoretic mobility being only determined by its
      electrostatic charge and hydrodynamic properties. In addition, the nonreduced
      protein cannot be blotted to a membrane. Unfolding of the protein upon reduction
      of its disulfide bridges enables electrotransference to membranes due to a
      restricted diffusion along the electrophoresis gel.

PMID- 16110466
TI  - Focused electrophoretic motion and selected electrokinetic dispensing of
      particles and cells in cross-microchannels.
AB  - The electrokinetic focusing and the resultant accelerated electrophoretic motion
      of polystyrene particles and red blood cells were visualized in microfluidic
      cross-channels. The experimentally measured width of the focused stream and the
      measured velocity increase of particles and cells at different voltage ratios
      follow the proposed analytical formula within the experimental error. The
      attained velocity increase is insensitive to the particle size, particle property
      (i.e., particle or cell), and particle trajectory. By solving the electrical
      potential field in the cross-channel at the experimental conditions, we
      demonstrate that the squeezed electrical field lines in the channel intersection
      determine the shape of the focused stream, and the nonuniform distribution of
      axial electrical field strength underlies the variation of particle/cell
      electrophoretic velocity through the focusing region. However, the
      dielectrophoretic force resulting from the nonuniform electrical field in the
      intersection seems to push the acceleration region of particles and cells
      slightly in the downstream direction. We have also achieved the single
      particle/cell dispensing by instantly triggering an electrical pulse
      perpendicular to the focused particulate flow in a double-cross microchannel. The
      electrokinetic manipulation of particle/cell in microchannels demonstrated in
      this work can be used for developing integrated lab-on-a-chip devices for studies
      of cells.

PMID- 16110467
TI  - Two-dimensional separation system of coupling capillary liquid chromatography to
      capillary electrophoresis for analysis of Escherichia coli metabolites.
AB  - A two-dimensional (2-D) separation system of coupling chromatography to
      electrophoresis was developed for profiling Escherichia coli metabolites.
      Capillary liquid chromatography (LC) with a monolithic silica-octadecyl silica
      column (500 x 0.2 mm ID) was used as the first dimension, from which the effluent
      fractions were further analyzed by capillary electrophoresis (CE) acting as the
      second dimension. Field-enhanced stacking was selectively employed as a
      concentration strategy to interface the two dimensions, which proved to be
      beneficial for the detection of metabolites. An artificial sample containing 118
      standards, some of which lack chromophores or have weak UV absorbance, was used
      to optimize the 2-D separation system. Under the optimum conditions, 63
      components in the artificial sample having absorbance at 254 nm could be well
      resolved and detected. The utility of the system was demonstrated by
      comprehensive analysis of E. coli metabolites. Comparing with the previous 2-D
      separation system we published in Anal. Chem. 2004, 76, 1419-1428, using a longer
      monolithic column in the first dimension improved the separation efficiency and
      offered the possibility of increasing the injection volume without compromising
      the separation efficiency. In the second dimension, field-enhanced stacking was
      used to improve the concentration sensitivity of the metabolites, and more
      metabolites in E. coli cell extract were detected and identified using the
      developed 2-D separation system. In addition, preliminary investigation for
      future CE-mass spectrometry coupling was also made in the study by using volatile
      buffers in the capillary LC and CE techniques.

PMID- 16110468
TI  - Application of cyclodextrin-mediated capillary electrophoresis to determine the
      apparent binding constants and thermodynamic parameters of the alkylnaphthalene
      derivatives.
AB  - The separation and migration behavior of seven positional and structural neutral
      alkylnaphthalene derivatives in cyclodextrin-mediated capillary electrophoresis
      were systematically investigated. The effective separation conditions were to use
      10 mM phosphate buffer with negatively charged carboxymethyl-beta-cyclodextrin
      (CM-beta-CD) at pH 6.0. The guest-host interactions with 1:1 or both 1:1 and 1:2
      binding stoichiometries for various derivatives were evaluated by comparing their
      apparent binding constants. The results reveal that the substituent group(s)
      attached to the naphthalene ring significantly affected the inclusion
      stoichiometric behaviors. Alkylnaphthalene derivatives with the substituent(s) at
      the 1-position(s), such as 1-ethylnaphthalene, 1,4-dimethylnaphthalene, may
      undergo complexation with one and two CM-beta-CD molecules. The binding constants
      of these derivatives were consistent with the data obtained by a
      spectrophotometric method. The thermodynamic parameters were also calculated in
      order to improve our understanding of the interaction between the neutral
      alkylnaphthalene derivatives and CM-beta-CD at various temperatures. The positive
      entropy (deltaS degrees) values of the alkylnaphthalenes with the substituent(s)
      at the 2-position(s) indicate that the inclusion of the guest molecule into the
      cavity of CM-beta-CD is favored at all temperatures.

PMID- 16110469
TI  - Identification of Op18/stathmin as a potential target of ASK1-p38 MAP kinase
      cascade.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein (MAP)
      kinase kinase kinase that activates the JNK and p38 MAP kinase cascades and has a
      broad range of biological activities including cell differentiation and stress
      induced apoptosis. However, effector molecules of ASK1-MAP kinase cascades that
      exert such activities have not been fully identified. Here we have identified
      oncoprotein 18 (Op18)/stathmin as a potential target of the ASK1-p38 cascade. By
      two-dimensional electrophoresis, phosphorylation of Op18/stathmin was found to be
      increased upon the expression of constitutively active ASK1 (ASK1DeltaN) in PC12
      cells. The ASK1-dependent increase in the phosphorylation of Op18/stathmin was
      attenuated by the treatment with SB203580, suggesting that p38alpha and/or
      p38beta contribute to the phosphorylation of Op18/stathmin. Consistently, we
      found that all four isoforms of p38 directly phosphorylated Op18/stathmin
      primarily at serine 25 in vitro. Taken together with the quantitative RT-PCR data
      indicating that p38alpha was the dominantly expressed isoform in PC12 cells, ASK1
      induced phosphorylation of Op18/stathmin appears to be mediated mainly through
      p38alpha in these cells. Given that the microtubule-destabilizing activity of
      Op18/stathmin is regulated by its phosphorylation, the ASK1-p38 cascade may
      regulate microtubule dynamics through Op18/stathmin.

PMID- 16110470
TI  - Role of cyclic-AMP responsive element binding (CREB) proteins in cell
      proliferation in a rat model of hepatocellular carcinoma.
AB  - The role of cyclic adenosine monophosphate (cAMP) is poorly understood in the
      regulation of normal and abnormal hepatic cell growth. In this study, we examined
      the regulation of intracellular cAMP levels and its effect on nuclear cAMP
      responsive elements (CREs) in a rat model of hepatocellular carcinoma (HCC).
      Tumorigenic liver cells were cultured from an in vivo model of HCC and the role
      of cAMP in cell mitogenesis determined. These data demonstrated agents that
      elevate intracellular cAMP ([cAMP]i) levels caused significant dose-dependent
      inhibition of serum-stimulated mitogenesis in HCC cells. Cells were next analyzed
      for transcription factor expression and activity following increased [cAMP]i.
      These data demonstrated time- and dose-dependent increases in CRE binding protein
      (pCREB) activity, a maximal response occurring after 10-20 min before returning
      to basal levels within 60 min. In contrast, increased [cAMP]i levels led to
      sustained inducible cAMP early repressor (ICER) II/IIgamma mRNA and protein
      induction. To understand these data in relation to the in vivo setting, HCC
      tumors were analyzed and compared to pair-matched normal liver (NL) samples.
      These studies demonstrated significantly elevated Gsalpha-protein expression in
      HCC versus NL in the absence of significant changes in basal cAMP levels.
      Analysis of total and active CREB demonstrated significantly increased total
      CREB/pCREB in HCC versus NL. Further analysis of CRE expression demonstrated
      significantly increased expression of ICER mRNA and protein in HCC versus sham
      operated (Sh). These data demonstrate cAMP, while capable of stimulating
      promitogenic CREB activation inhibits cell mitogenesis in HCC possibly via ICER
      induction.

PMID- 16110471
TI  - Determination and pharmacokinetic study of chlorogenic acid in rat dosed with Yin
      Huang granules by RP-HPLC.
AB  - A reversed-phase high-performance liquid chromatographic (RP-HPLC) method was
      described for the determination of chlorogenic acid (CGA) in rat plasma using
      protocatechuic acid as internal standard (IS). CGA in plasma was extracted with
      acetonitrile, which also acted as deproteinization agent. Chromatographic
      separation was performed on a Kromasil C18 column with methanol-0.2 m acetic acid
      (pH 3.0, 25:75, v/v) as mobile phase at a flow-rate of 1.0 mL/min with an
      operating temperature of 30 degrees C and UV detection at 300 nm. The standard
      curve was found to be linear over the concentration ranges of 0.4-2.5 microg/mL
      and 2.5-40 microg/mL, and the limit of quantification (LOQ) was 0.4 microg/mL.
      The analytical precision and accuracy were validated by relative standard
      deviation (RSD) and relative error, which were in ranges 3.14-10.78% and -2.20
      5.00%, respectively. The average recovery of CGA was 87.59%. The method was
      successfully applied to the pharmacokinetic study of CGA in Yin-Huang granules.

PMID- 16110472
TI  - Derivatization chemistries for determination of serotonin, norepinephrine and
      dopamine in brain microdialysis samples by liquid chromatography with
      fluorescence detection.
AB  - The present paper provides an overview on currently developed derivatization
      chemistries and techniques for determination of monoamine neurotransmitters
      serotonin (5-HT), norepinephrine (NE) and dopamine (DA) in microdialysis samples
      by microbore liquid chromatography with fluorescence detection. In mild alkaline
      conditions, 5-hydroxyindoles and catecholamines react with benzylamine (BA),
      forming highly fluorescent 2-phenyl-4,5-pyrrolobenzoxazoles and 2-phenyl(4,5
      dihydropyrrolo) [2,3-f]benzoxazoles, respectively. However, for derivatization of
      DA a higher fluorescence intensity was achieved for reaction with 1,2
      diphenylethylenediamine (DPE) rather than with BA, therefore for simultaneous
      determination of 5-HT, NE and DA in brain microdialysates, a two-step
      derivatization with BA followed by DPE was developed. The detection limits for 5
      HT, NE and DA were 0.2, 0.08 and 0.13 fmol, respectively, in an injection volume
      of 20 microL, which corresponds to concentrations of 30, 12 and 19.5 pm,
      respectively in standard solution prior to derivatization. The experimental data
      presented demonstrate the ability of the technique to simultaneously monitor
      neuronally releasable pools of monoamine neurotransmitters in the rat and mouse
      brains at basal conditions and following pharmacological treatments or
      physiological stimuli. These techniques play an important role in drug discovery
      and clinical investigation of psychiatric and neurological diseases such as
      depression, schizophrenia and Parkinson's disease.

PMID- 16110473
TI  - Myostatin negatively regulates the expression of the steroid receptor co-factor
      ARA70.
AB  - Myostatin is a transforming growth factor-beta (TGF-beta) superfamily member and
      a key negative regulator of embryonic and postnatal muscle growth. In order to
      identify downstream target genes regulated by Myostatin, we performed suppressive
      subtraction hybridization (SSH) on cDNA generated from the biceps femoris muscle
      of wild-type and myostatin-null mice. Sequence analysis identified several known
      and unknown genes as Myostatin downstream target genes. Here, we have
      investigated the regulation of gene expression of an androgen receptor (AR)
      binding co-factor, androgen receptor associated protein-70 (ARA70), by Myostatin.
      We show that in mouse there are two isoforms of ARA70 with high homology (79%) to
      human ARA70; an alpha-isoform which is a canonical ARA70 and a beta-isoform which
      has a 9 consecutive amino acid deletion and 6 amino acid substitutions in the
      carboxyl-terminal portion. Reverse Northern analysis on the differentially
      expressed cDNA library indicated that there is increased expression of ARA70 in
      the muscles of myostatin-null mice. In addition, Northern blot, together with
      semi-quantitative PCR analysis, confirmed that there is increased expression of
      ARA70 in myostatin-null biceps femoris muscle when compared to wild-type muscle.
      In corroboration of these results, addition of exogenous Myostatin results in
      down-regulation of ARA70 expression confirming that Myostatin is a negative
      regulator of ARA70 gene expression. Expression analysis further confirmed that
      ARA70 is up-regulated during myogenesis and that peak expression of ARA70 is
      observed following the peak expression of MyoD in differentiating myoblasts.
      Given that lack of Myostatin and increased expression of AR leads to hypertrophy,
      we propose that absence of Myostatin, at least in part, induces the hypertrophy
      phenotype by increasing the activity of AR by up-regulating the expression of
      ARA70, a known stimulating co-factor of AR.

PMID- 16110474
TI  - Myostatin auto-regulates its expression by feedback loop through Smad7 dependent
      mechanism.
AB  - Myostatin, a secreted growth factor, is a member of the TGF-beta superfamily and
      an inhibitor of myogenesis. Previously, we have shown that myostatin gene
      expression is regulated at the level of transcription and that myostatin is a
      downstream target gene of MyoD. Here we show that myostatin gene expression is
      auto-regulated by a negative feedback mechanism. Northern blot analysis indicated
      that there are relatively higher levels of myostatin mRNA in the biceps femoris
      muscle of cattle that express a non- functional myostatin allele (Belgian Blue)
      as compared to normal cattle. In contrast, addition of exogenous myostatin
      decreases endogenous myostatin mRNA. Consistent with this result, wild type
      myostatin protein is able to repress myostatin promoter activity via Activin type
      IIb receptor (ActRIIB) and ALK5 (P < 0.001). However, non-functional myostatin
      (Piedmontese) failed to repress the myostatin promoter suggesting that myostatin
      auto-regulates its promoter by negative feedback inhibition. Auto-regulation by
      myostatin appears to be signaled through Smad7, since the expression of the
      inhibitory Smad7 is induced by myostatin and the over-expression of Smad7 in turn
      inhibits the myostatin promoter activity (P < 0.001). In contrast down regulation
      of Smad7 by siRNA results in increased myostatin mRNA indicating that Smad7 is a
      negative regulator of myostatin gene expression. Consistent with these results, a
      decrease in Smad7 mRNA and concomitant increase in myostatin expression is seen
      in myotubes that express non functional myostatin. In addition, interference with
      myostatin signaling prevents the induction of Smad7 promoter activity by
      myostatin. Based on these results, we propose that myostatin auto-regulates its
      gene expression through a Smad7 dependent mechanism in myogenic cells.

PMID- 16110475
TI  - Sexual dimorphism of cusp dimensions in human maxillary molars.
AB  - Cusp dimensions of human maxillary molars were compared between males and females
      to determine whether the later-developed, distal cusps displayed greater sexual
      dimorphism than the earlier-developed, mesial cusps, and whether the later
      forming second molar displayed greater sexual dimorphism than the first molar.
      First and second permanent molar crowns (M1 and M2) were measured indirectly,
      using dental casts obtained from 117 Japanese (65 males and 52 females).
      Measurements included maximum mesiodistal and buccolingual crown diameters and
      the diameters of the four main cusps: the paracone, protocone, metacone, and
      hypocone. Mean values of crown dimensions were larger in males than in females
      for both M1 and M2, but the sexual difference in protocone diameter of M1 was not
      significant. The protocone in M1 showed the least amount of sexual dimorphism,
      followed by the metacone, hypocone, and paracone, while in M2, the percentage
      sexual dimorphism corresponded to the order of cusp formation: paracone,
      protocone, metacone, and hypocone. With the exception of the paracone diameter,
      M2 showed greater sexual dimorphism than M1. Sexual dimorphism was not always
      greater in the later-developed, distal cusps of M1 or M2, but the protocone, the
      most important cusp in terms of occlusal function, displayed the least dimorphism
      in M1.

PMID- 16110476
TI  - Morphometric analysis of lumbar vertebrae in extinct Malagasy strepsirrhines.
AB  - Previous research on subfossil lemurs has revealed much about the positional
      behavior of these extinct strepsirrhines, but a thorough quantitative analysis of
      their vertebral form and function has not been performed. In this study, 156
      lumbar vertebrae of Pachylemur, Archaeolemur, Megaladapis, Mesopropithecus,
      Babakotia, and Palaeopropithecus (11 species in all) were compared to those of 26
      species of extant strepsirrhines and haplorhines. Lumbar shape was compared among
      species, using a principal components analysis (PCA) in conjunction with selected
      vertebral indices. The first principal component revealed strong separation
      between Palaeopropithecus at one extreme, and Archaeolemur/Pachylemur at the
      other, with Babakotia, Mesopropithecus, and Megaladapis in an intermediate
      position. Palaeopropithecus has markedly shorter spinous processes and wider
      laminae than do the other subfossil taxa, consistent with sloth-like, inverted
      suspensory postures. The moderately reduced lumbar spinous processes of
      Babakotia, Mesopropithecus, and Megaladapis are convergent with those of lorisids
      and Pongo, reflecting antipronogrady, but a less specialized adaptation than that
      of Palaeopropithecus. Archaeolemur and Pachylemur share relatively elongated
      spinous processes, in conjunction with other features (e.g., transverse process
      orientation and relatively short vertebral bodies) indicative of pronograde,
      quadrupedal locomotion characterized by reduced agility. All subfossil taxa
      exhibit adaptations emphasizing lumbar spinal stability (e.g., relatively short
      vertebral bodies, and transverse processes that are not oriented ventrally); we
      believe this probably reflects convergent mechanical demands connected to large
      body size, irrespective of specific locomotor mode. Reconstructions of positional
      behavior in subfossil lemurs based on lumbar vertebrae are largely consistent
      with those based on other aspects of the postcrania.

PMID- 16110477
TI  - Dispersal of epithelial cancer cell colonies by lysophosphatidic acid (LPA).
AB  - We describe a model system in which cancer cell colonies disperse into single,
      highly migratory cells in response to lysophosphatidic acid (LPA). Though LPA is
      known to stimulate chemotaxis and chemokinesis, a colony dispersal effect has not
      been reported, to our knowledge. Cancer colony dispersal by LPA is comprised of
      an ordered sequence of events: (1) stimulation of membrane ruffling and formation
      of lamellipodia, (2) dissolution of adherens junctions, (3) single cell migration
      in a mesenchymal-like morphology we term "ginkgo-leaf." The net result is
      dispersal of carcinoma cells from a compact colony. We analyzed these three steps
      using live-cell imaging and computer-assisted quantification and measured the
      following parameters: onset of lamellipodia formation, lamellipodia velocity,
      colony dispersal, trans-epithelial resistance, migrating cell number and speed.
      Because hepatocyte growth factor (HGF) was described as an epithelial scatter
      factor, we compared it to LPA in our system and found that HGF has no epithelial
      colony dispersal properties and that this effect is strictly related to LPA.
      Given its striking similarity to tumor cell budding observed in patients, we
      propose that LPA-colony dispersal may provide a cellular mechanism underlying
      cancer invasion and as such deserves further studies.

PMID- 16110478
TI  - Nuclear envelope barrier leak induced by dexamethasone.
AB  - Nuclear pore complexes (NPCs) are multiprotein channels that span the nuclear
      envelope. They strongly limit the efficiency of gene transfection by restriction
      of nuclear delivery of exogenously applied therapeutic macromolecules. NPC
      dilation could significantly increase this efficiency. Recently, it was shown in
      oocytes of Xenopus laevis that NPCs dilate from about 82 to 110 nm within min
      after injection of the glucocorticoid analog dexamethasone (dex). In the present
      paper we analyzed by means of atomic force microscopy the structural details of
      NPC dilation and correlated them with functional changes in nuclear envelope
      permeability. 5-11 min after Dex injection NPC dilation was found at its maximum
      (approximately 140 nm). In addition, a yet unknown configuration, so-called giant
      pore, up to 300 nm in diameter, was visualized. Giant pore formation was
      paralleled by an increase in nuclear envelope permeability tested by
      electrophysiology and confocal fluorescence microscopy. Even large macromolecules
      lacking any nuclear localization signal (77 kDa FITC-dextran, molecule diameter
      up to 36 nm) could gain access to the nucleus. We conclude that dex transiently
      opens unspecific pathways for large macromolecules. Dex treatment could be
      potentially useful for improving the efficiency of nuclear gene transfection.

PMID- 16110479
TI  - Bilateral asymmetry in the limb bones of the chimpanzee (Pan troglodytes).
AB  - There is much debate in behavioral primatology on the existence of population
      level handedness in chimpanzees. The presence or absence of functional laterality
      in great apes may shed light on the origins of human handedness and on the
      evolution of cerebral asymmetry. The plasticity of long bone diaphyses in
      response to mechanical loading allows the functional interpretation of
      differences in cross-sectional geometric. While left-right asymmetry in upper
      limb diaphyseal morphology is a known property in human populations, it remains
      relatively unexplored in apes. We studied bilateral asymmetry in 64 skeletons of
      wild-caught chimpanzee using the humerus, second metacarpal, and femur. The total
      subperiosteal area (TA) of the diaphyses was measured at 40% of maximum humeral
      length and at the midshaft of the metacarpals and femora using external silicone
      molds. Overall, the TA values of the left humeri were significantly greater than
      the right, indicating directional asymmetry. This effect was even greater when
      the magnitude of difference in TA between each pair of humeri was compared. The
      right second metacarpals showed a tendency toward greater area than did the left,
      but this did not reach statistical significance. The lack of asymmetry in the
      femur serves as a lower limb control, and suggests that the upper limb results
      are not a product of fluctuating asymmetry. These findings imply behavioral
      laterality in upper limb function in chimpanzees, and suggest a complementary
      relationship between precision and power.

PMID- 16110480
TI  - Overexpression of hyaluronan synthases alters vascular smooth muscle cell
      phenotype and promotes monocyte adhesion.
AB  - Hyaluronan (HA) accumulates in vascular disease but its functional role is not
      fully understood. To investigate the impact of HA enriched extracellular matrices
      (ECM) on cell phenotype, arterial smooth muscle cells (ASMCs) were transduced
      with retroviral constructs (LXSN) encoding murine has-1, has-2, and has-3. HA
      synthesis was significantly elevated in has transduced ASMCs. Metabolically
      labeled HA from has-1 and has-2 transduced cells was present mostly in high
      molecular weight (HWA) fractions (2-10x10(6) Da), whereas HA produced by has-3
      and control cells was present in lower molecular weight fractions (approximately
      2x10(6) Da). Both has-1 and has-3 transduced ASMCs accumulated more pericellular
      HA than has-2 transduced ASMCs. All has transduced ASMCs had attenuated growth
      and migration rates, and a decreased detachment response. Affinity histochemistry
      revealed that has-1 transduced ASMCs accumulated the greatest amount of HA
      containing ECM than the other transduced ASMCs. This ECM was hyaluronidase
      sensitive and bound a significantly greater number of monocytes than the ECM
      generated by has-2 or has-3 transduced ASMCs. Confocal microscopy showed CD44
      positive monocytes bound to hyaluronidase sensitive ECM in has-1 transduced
      ASMCs. These data implicate specific has isoforms in the formation of HA enriched
      pro-inflammatory ECMs.

PMID- 16110481
TI  - p53 and the malignant progression of Barrett's esophagus.
AB  - Barrett's esophagus (BE) is a metaplastic disorder in which specialized columnar
      epithelium replaces healthy squamous epithelium (intestinal metaplasia). Even
      though its pathophysiology and the steps of its neoplastic progression are not
      completely understood, BE can be considered as a complication of gastroesophageal
      reflux disease (GERD). Given that esophageal adenocarcinoma, which is continually
      increasing in the Western world, still has a poor prognosis and suffers from late
      diagnosis, and because BE is a precancerous lesion, there is a strong need for
      good molecular markers of malignant progression in Barrett's metaplasia (BM). The
      aim of this review is to examine the published data regarding the role that
      assessment of p53 may play in the management of BE, trying to understand if it
      may be a useful marker to early diagnose BE malignant transformation.

PMID- 16110482
TI  - Phosphoinositide 3-kinasegamma (PI3Kgamma) controls L-type calcium current
      (ICa,L) through its positive modulation of type-3 phosphodiesterase (PDE3).
AB  - The modulation of L-type calcium current (ICa,L) is mainly due to mediators
      acting through activation of G protein-coupled receptors (GPCR) and different
      protein kinases; among them, phosphoinositide 3-kinasegamma (PI3Kgamma) has been
      recently discovered to play an important role in the regulation of cardiac
      contractility and beta-adrenergic signal transduction. Recent reports have
      demonstrated that, in the heart, different subtypes of beta-adrenergic receptors
      are coupled to both Gi and/or Gs proteins. While beta1-adrenergic receptors
      (beta1-AR) couple only to Gs and evoke a strong ICa,L, beta2-adrenergic receptors
      (beta2-AR) can activate both Gs and Gi proteins and trigger only a limited ICa,L.
      Here we demonstrate that (i) PI3Kgamma-/- ventricular myocytes are characterized
      by an higher basal ICa,L density, even if the responsiveness of adenylyl cyclase
      to Forskolin is comparable to that observed in PI3Kgamma+/+ cardiomyocytes; (ii)
      both in basal conditions and after beta-AR stimulation, the activity of
      phosphodiesterase (PDE) type 3 depends on PI3Kgamma; (iii) in PI3Kgamma-/-
      cardiac myocytes, specific stimulation of beta2-AR is followed by a increase in
      ICa,L stronger than in wild-type controls. Taken together, our results suggest
      that the higher values of ICa,L observed both in basal conditions and after beta
      AR stimulation in PI3Kgamma-/- ventricular myocytes are mainly due to a positive
      modulation of PDE3 activity exerted by PI3Kgamma. As observed in PI3Kgamma-/-
      neonatal cardiomyocytes, cells lacking PI3Kgamma are more sensitive to
      stimulation of beta2-adrenergic receptors.

PMID- 16110483
TI  - Leptin and cancer.
AB  - The prevalence of obesity has markedly increased over the past two decades,
      especially in the industrialized countries. While the impact of excess body
      weight on the development of cardiac disease and diabetes has been well
      documented, the link between obesity and carcinogenesis is just being recognized.
      This review will focus on the link between leptin, a cytokine that is elevated in
      obese individuals, and cancer development. First, we briefly discuss the
      biological functions of leptin and its signaling pathways. Then, we summarize the
      effects of leptin on different cancer types in experimental cellular and animal
      models. Next, we analyze epidemiological data on the relationship between obesity
      and the presence of cancer or cancer risk in patients. Finally, leptin as a
      target for cancer treatment and prevention will be discussed.

PMID- 16110484
TI  - Pubertal timing, hormones, and body composition among adolescent Turkana males.
AB  - The Turkana, like other East African pastoral groups, are known for their tall
      adult stature, achieved despite a blunted growth spurt during adolescence and
      continued growth into the early 20s. To investigate the hormonal mechanisms
      associated with the pattern of slow and continued adolescent growth, we collected
      data on hormonal status, height, weight, and trunk skinfolds and ethnographic
      self-reports of testicular maturation in a cross-sectional sample of 35 nomadic
      and 37 settled Turkana males aged 14-24. Hormonal determinations included
      testosterone (T), sex hormone-binding globulin (SHBG), and dehydroepiandrosterone
      (DHEA) in blood, in addition to urinary DHEA. Self-reports of testicular
      maturation showed no difference between settled and nomadic subpopulations.
      However, nomadic boys exhibited significantly higher levels of T, DHEA, and SHBG.
      Of all the hormones, only SHBG showed a significant relationship with age.
      Multiple regression models show blood T and SHBG to be significant independent
      predictors of achieved height as well as weight, controlling for age. Our results
      suggest that onset of puberty is substantially delayed among Turkana males, and
      that bioavailable T is related to growth in stature during adolescence. We
      suggest that SHBG acts to mediate the effects of energy availability on
      adolescent growth in this energetically limited population. Our findings may also
      have implications for understanding adolescent growth among Homo erectus.

PMID- 16110485
TI  - Intrachromosomal serial replication slippage in trans gives rise to diverse
      genomic rearrangements involving inversions.
AB  - Serial replication slippage in cis (SRScis) provides a plausible explanation for
      many complex genomic rearrangements that underlie human genetic disease. This
      concept, taken together with the intra- and intermolecular strand switch models
      that account for mutations that arise via quasipalindrome correction, suggest
      that intrachromosomal SRS in trans (SRStrans) mediated by short inverted repeats
      may also give rise to a diverse series of complex genomic rearrangements. If this
      were to be so, such rearrangements would invariably generate inversions. To test
      this idea, we collated all informative mutations involving inversions of >or=5 bp
      but <1 kb by screening the Human Gene Mutation Database (HGMD; www.hgmd.org) and
      conducting an extensive literature search. Of the 21 resulting mutations, only
      two (both of which coincidentally contain untemplated additions) were found to be
      incompatible with the SRStrans model. Eighteen (one simple inversion, six
      inversions involving sequence replacement by upstream or downstream sequence,
      five inversions involving the partial reinsertion of removed sequence, and six
      inversions that occurred in a more complicated context) of the remaining 19
      mutations were found to be consistent with either two steps of intrachromosomal
      SRStrans or a combination of replication slippage in cis plus intrachromosomal
      SRStrans. The remaining lesion, a 31-kb segmental duplication associated with a
      small inversion in the SLC3A1 gene, is explicable in terms of a modified SRS
      model that integrates the concept of "break-induced replication." This study
      therefore lends broad support to our postulate that intrachromosomal SRStrans can
      account for a variety of complex gene rearrangements that involve inversions.

PMID- 16110486
TI  - Mutations in the human LKB1/STK11 gene.
AB  - The human LKB gene (official HUGO symbol, STK11) encodes a serine/threonine
      protein kinase that is defective in patients with Peutz-Jeghers syndrome (PJS).
      PJS is an autosomal dominantly inherited syndrome characterized by hamartomatous
      polyposis of the gastrointestinal tract and mucocutaneous pigmentation. To date,
      145 different germline LKB1 mutations have been reported. The majority of the
      mutations lead to a truncated protein product. One mutational hotspot has been
      observed. A 1-bp deletion and a 1-bp insertion at the mononucleotide repeat (C6
      repeat, c.837-c.842) between the codons 279-281 have been found in six and seven
      unrelated PJS families, respectively. However, these mutations account only for
      approximately 7% of all mutations identified in the PJS families (13/193). A
      review of the literature provides a total of 40 different somatic LKB1 mutations
      in 41 sporadic tumors and seven cancer cell lines. Mutations occur particularly
      in lung and colorectal cancer. Most of the somatic LKB1 mutations result in
      truncation of the protein. A mutational hotspot seems to be a C6 repeat
      accounting for 12.5% of all somatic mutations (6/48). These results are
      concordant with the germline mutation spectrum. However, the proportion of the
      missense mutations seems to be higher among the somatic mutations (45%) than
      among the germline mutations (21%), and only seven of the mutations are exactly
      the same in both of the mutation types.

PMID- 16110487
TI  - Trauma-induced changes in diaphyseal cross-sectional geometry in two elites from
      Copan, Honduras.
AB  - This research utilized biplanar radiographs to estimate cross-sectional
      biomechanical properties for the skeletal remains of two elite individuals from
      the Early Classic period (ca. AD 400-600) of Copan, Honduras: K'inich Yax K'uk'
      Mo' (Hunal Burial 95-2), founder of the Early Classic Dynasty at Copan, and the
      primary female interment (Burial 37-8) from the Motmot tomb. Both individuals
      survived severe blunt-force insults to the right forearm. Gross skeletal
      examination and evaluation of the radiographs for K'inich Yax K'uk' Mo' suggest
      that these traumas resulted from, at least in part, disuse atrophy of the
      affected forearm skeletal elements. Gross and radiologic evaluation of the Motmot
      remains countered the possibility that she suffered from a metabolic bone
      disease, and confirmed the presence of a well-healed parry fracture of the right
      ulna. The degree of asymmetry in cross-sectional biomechanical properties
      reported here for K'inich Yax K'uk' Mo' is likely the secondary result of the
      described blunt-force trauma. The results obtained for the principal Motmot
      interment are not as dramatic, but suggest subtle changes to humeral cross
      sectional geometry subsequent to trauma.

PMID- 16110488
TI  - Genetic variation, nucleotide diversity, and linkage disequilibrium in seven
      telomere stability genes suggest that these genes may be under constraint.
AB  - To maintain chromosomal integrity and to protect the ends of chromosomes against
      recognition as damaged DNA, end-to-end fusion, or recombination, a coordinated
      set of genes is required to stabilize the telomere. We surveyed common genetic
      variation in seven genes that are vital to telomere stability (TERT, POT1, TNKS,
      TERF1, TINF2, TERF2, and TERF2IP) and validated single nucleotide polymorphisms
      (SNPs) in four different ethnic groups (n=118 total). Overall, our data show
      limited degrees of nucleotide diversity in comparison with data from other gene
      families. We observed that these genes are highly conserved in sequence between
      species, and that for nearly all of the coding SNPs the most common allele is
      ancestral (i.e., it is observed in primate sequences). Our findings support the
      hypothesis that genetic variation in a pathway that is critical for telomere
      stability may be under constraint. These data establish a foundation for further
      investigation of these genes in population-genetics, evolution, and disease
      association studies.

PMID- 16110489
TI  - Topographic guidance of endothelial cells on silicone surfaces with micro- to
      nanogrooves: orientation of actin filaments and focal adhesions.
AB  - To mimic the uniformly elongated endothelium in natural linear vessels, bovine
      aortic endothelial cells (BAECs) are cultured on micro- to nanogrooved, model
      poly(dimethylsiloxane) (PDMS) substrates preadsorbed with about 300 ng/cm(2) of
      fibronectin. BAEC alignment, elongation, and projected area were investigated for
      channel depths of 200 nm, 500 nm, 1 microm, and 5 microm, as well as smooth
      surfaces. Except for the 5 microm case, the ridge and channel widths were held
      nearly constant about 3.5 microm. With increasing channel depth, the percentage
      of aligned BAECs increased by factors of 2, 2, 1.8, and 1.7 for 1, 4, 24, and 48
      h. Maximum alignment, about 90%, was observed for 1 microm deep channels at 1 h.
      The alignment of BAECs on grooved PDMS was maintained at least until cells
      reached near confluence. F-actin and vinculin at focal adhesions also aligned
      with channel direction. Analysis of confocal microscopy images showed that focal
      adhesions localized at corners and along the sidewalls of 1-microm deep channels.
      In contrast, focal adhesions could not form on the bottom of the 5-microm deep
      channels. Cell proliferation was similar on grooved and smooth substrates. In
      summary, PDMS substrates engraved with micro- and nanochannels provide a powerful
      method for investigating the interplay between topography and cell/cytoskeletal
      alignment.

PMID- 16110490
TI  - The in vitro growth and activity of sheep osteoblasts on three-dimensional
      scaffolds from poly(L/DL-lactide) 80/20%.
AB  - Critical-size bone defects usually require the use of autogenous bone grafts to
      heal. Harvesting of bone is traumatic, and results in high morbidity of donor
      site. A potential alternative to bone graft may be a bone substitute with
      adequate biocompatibility and biological properties produced from ceramics and/or
      bioresorbable or biodegradable polymers. In the present study, sheep osteoblasts
      isolated from cancellous bone chips were seeded and cultured for 1, 2, and 3
      weeks on porous poly(L/DL-lactide) 80/20% scaffolds. The cell morphology was
      assessed from rhodamine staining and scanning electron microscopy, cell growth,
      and activity from the measurements of DNA, alkaline phosphatase activity, and
      total protein amount in the cell lysate, and mineral deposits from EDAX and van
      Kossa staining. The cells attached firmly to the scaffold walls, grew deeply into
      the pores, and exhibited morphology typical of osteoblasts. Mineralized noduli
      with a Ca/P ratio of 1.4 to 1.8 found in the scaffold indicated that the cells
      had maintained their osteoblastic phenotype. The amount of DNA, alkaline
      phosphatase activity, and the total amount of proteins increased with time of
      culturing, although at 3 weeks the cells did not yet reach the contact
      inhibition. These results demonstrate that three-dimensional porous poly(L/DL
      lactide) 80/20% scaffolds provide a suitable substrate for the attachment and
      growth of primary osteoblasts, and might potentially be used as bone defect
      fillers and in the design of tissue-engineered bone substitutes.

PMID- 16110491
TI  - Loss of mitochondrial membrane potential is associated with increase in
      mitochondrial volume: physiological role in neurones.
AB  - Mitochondrial volume homeostasis is a housekeeping cellular function, thought to
      help regulate oxidative capacity, apoptosis, and mechanical signaling. The volume
      is mainly regulated by potassium flux into and out of the matrix and controlled
      by the electrochemical potential. Mitochondrial depolarization will therefore
      affect this flux but studies showing how have not been consistent, and it is
      unclear what mitochondrial volume changes also occur. The aim of the present
      study was to investigate mitochondrial volume changes in permeabilized neurons
      under various bioenergetic conditions using deconvolution confocal microscopy.
      Under control conditions, mitochondria in situ appeared rod-shaped with mean
      length, surface area, and volume values of 2.29+/-0.10 microm, 1.41+/-0.10
      microm2, and 0.062+/-0.006 microm3, respectively (n=42). Valinomycin, a K+
      selective ionophore, increased mitochondrial volume by 63+/-22%, although surface
      area was almost unchanged because mitochondrial shape became more spherical.
      Pinacidil, an opener of mitochondrial ATP-dependent channels, produced similar
      effects, although some mitochondria were insensitive to its action. Mitochondrial
      depolarization with the protonophore FCCP, or with respiratory chain inhibitors
      antimycin and sodium azide was associated with a considerable increase in
      mitochondrial volume (by 75%-140%). Effects of mitochondrial modulators were also
      studied in intact neurones. Tracking of single mitochondria showed that during
      65+/-2% of their time, mitochondria were motile with an average velocity of
      0.19+/-0.01 microm/s. Antimycin, azide, and FCCP induced mitochondrial swelling
      and significantly decreased mitochondrial motility. In the presence of pinacidil,
      swollen mitochondria had reduced their motility, although mitochondria with
      normal volume stayed motile. These data show that mitochondrial depolarization
      was followed by significant swelling, which, in turn, impaired mitochondrial
      trafficking.

PMID- 16110492
TI  - Microtubule-dependent nuclear-cytoplasmic shuttling of Runx2.
AB  - RUNX/AML transcription factors are critical regulators of cell growth and
      differentiation in multiple lineages and have been linked to human cancers
      including acute myelogenous leukemia (RUNX1), as well as breast (RUNX2) and
      gastric cancers (RUNX3). RUNX proteins are targeted to gene regulatory micro
      environments within the nucleus via a specific subnuclear targeting signal.
      However, the dynamics of RUNX distribution and compartmentalization between the
      cytoplasm and nucleus is minimally understood. Here we show by immunofluorescence
      microscopy that RUNX2 relocates from the nucleus to the cytoplasm when
      microtubules are stabilized by the chemotherapeutic agent taxol. The taxol
      dependent cytoplasmic accumulation of RUNX2 is inhibited by leptomycin B, which
      blocks CRM-1 dependent nuclear export, and is not affected by the protein
      synthesis inhibitor cycloheximide. Using biochemical assays, we show that
      endogenous RUNX2 associates with stabilized microtubules in a concentration
      dependent manner and that the RUNX2 amino terminus mediates the microtubule
      association. In soluble fractions of cells, RUNX2 co-immunoprecipitates alpha
      tubulin suggesting that microtubule binding involves the alpha/beta tubulin
      subunits. We conclude that RUNX2 associates with microtubules and shuttles
      between the nucleus and the cytoplasm. We propose that nuclear-cytoplasmic
      shuttling of RUNX2 may modulate its transcriptional activity, as well as its
      ability to interface with signal transduction pathways that are integrated at
      RUNX2 containing subnuclear sites. It is possible that taxol-induced acute
      depletion of the nuclear levels of RUNX2 and/or other cell growth regulatory
      factors may represent an alternative pathway by which taxol exerts its biological
      effects during cancer chemotherapies.

PMID- 16110493
TI  - The effect of combined cyclic mechanical stretching and microgrooved surface
      topography on the behavior of fibroblasts.
AB  - Under the influence of mechanical stress, cultured fibroblasts have a tendency to
      orient themselves perpendicular to the stress direction. Similar cell alignment
      can be induced by guiding cells along topographical clues, like microgrooves. The
      aim of this study was to evaluate cell behavior on microgrooved substrates,
      exposed to cyclic stretching. We hypothesized that cellular shape is mainly
      determined by topographical clues. On basis of earlier studies, a 10-microm wide
      square groove, and a 40-microm wide V-shaped groove pattern were used. Smooth
      substrates served as controls. Onto all substrates fibroblasts were cultured and
      1-Hz cyclic stretching was applied (0, 4, or 8%) for 3-24 h. Cells were prepared
      for scanning electron microscopy, immunostaining of filamentous actin, alignment
      measurements, and PCR (collagen-I, fibronectin, alpha1- and beta1-integrins).
      Results showed that cells aligned on all grooved surfaces, and fluorescence
      microscopy showed similar orientation of intracellular actin filaments. After 3 h
      of stretch, cellular orientation started to commence, and after 24 h the cells
      had aligned themselves almost entirely. Image analysis showed better orientation
      with increasing groove depth. Statistical testing proved that the parameters
      groove type, groove orientation, and time all were significant, but the variation
      of stretch force was not. Substrates with microgrooves perpendicular to the
      stretch direction elicit a better cell alignment. The expression of beta1
      integrin and collagen-I was higher in the stretched samples. In conclusion, we
      can maintain our hypothesis, as microgrooved topography was most effective in
      applying strains relative to the long axis of the cell, and only secondary
      effects of stretch force were present.

PMID- 16110494
TI  - Rare missense variants in ATP1A2 in families with clustering of common forms of
      migraine.
AB  - Migraine is a recurrent neurovascular disease. Its two most common forms-migraine
      without aura (MO) and migraine with aura (MA)-both show familial clustering and a
      complex pattern of inheritance. Familial hemiplegic migraine (FHM) is a rare
      monogenic subform caused by mutations in the calcium channel gene CACNA1A or the
      Na(+)/K(+)-ATPase gene ATP1A2. An involvement of FHM genes in the pathogenesis of
      common forms of migraine is not proven. We therefore systematically screened
      ATP1A2 in families with several members affected by MA and/or MO. We identified
      two novel missense alterations [c.520G>A (p.E174 K) and c.1544G>A (p.C515Y)] in
      two out of 45 families, which were not found in 520 control chromosomes.
      Functional studies of these variants in Xenopus oocytes by two-electrode voltage
      clamp measurements and radiochemical determination of ATPase activity showed that
      C515Y leads to a complete loss of function comparable with the effect of FHM
      mutations whereas for E174 K no functional alteration could be found in the in
      vitro assays. In conclusion we propose that rare variants in ATP1A2 are involved
      in the susceptibility to common forms of migraine, because of 1) the absence of
      alterations in controls, 2) the particular pattern of segregation in both
      families, 3) the high conservation of mutated residues in Na(+)/K(+)-ATPases, 4)
      the functional effect of C515Y, and 5) the involvement of ATP1A2 in a monogenic
      form of migraine.

PMID- 16110495
TI  - Multidifferentiation potential of mesenchymal stem cells in three-dimensional
      collagen gel cultures.
AB  - Mesenchymal stem cells (MSCs) have a great therapeutic potential resulting from
      their ability to differentiate into multiple tissues when cultured under specific
      conditions. However, it has not been clearly demonstrated whether or not MSCs
      exhibit a multidifferentiation potential in three-dimensional collagen gel
      cultures. This study was conducted to explore the multidifferentiation potential
      of MSCs cultured in three-dimensional collagen gels. Human MSCs were cultured in
      0.3% collagen gel for 20 days in chondrogenic differentiation medium (CDM), and
      for 14 days in osteogenic differentiation medium (ODM). Increases in GAG
      deposits, intensity of toluidine blue staining, and mRNA expressions of
      chondrogenic markers (type II collagen and type X collagen) were found in human
      MSCs cultured in the collagen gel maintained in CDM. Positive staining for
      alkaline phosphatase (ALP) activity and alizarin red, and increases in mRNA
      expressions of osteogenic markers (type I collagen, bone sialoprotein and ALP)
      were noted in the MSCs maintained in ODM. These findings emphasize that human
      MSCs have an ability to differentiate into both bone and cartilaginous tissues in
      three-dimensional collagen gel cultures, indicating potential clinical
      applications of MSC transplant therapy with collagen gel as a scaffold for bone
      or cartilage regeneration in complicated tissue defects.

PMID- 16110496
TI  - Crosslinked chitosan: its physical properties and the effects of matrix stiffness
      on chondrocyte cell morphology and proliferation.
AB  - Chitosan [beta(1-4)-2 amino-2-deoxy-D-glucose], the natural polyaminosaccharide
      derived from N-deacetylation of chitin [beta(1-4)-2 acetamide-2-deoxy-D-glucose],
      has been shown to possess attractive biological and cell interactive properties.
      Recently chitosan and chitosan analogs have also been shown to support the growth
      and continued function of chondrocytes. In the present study, chitosan substrates
      are crosslinked with a functional diepoxide (1,4 butanediol diglycidyl ether) to
      alter its mechanical property, and the viability and proliferation of the canine
      articular chondrocytes seeded on the crosslinked surface are further assayed. Of
      interest is the impact of substrate stiffness on the growth and proliferation of
      articular canine chondrocytes. Crosslinked scaffolds were also subjected to
      degradation by chitosanase to examine the impact of crosslinking on enzyme
      assisted degradation. The hydrophilicity and compression modulus of the
      crosslinked surfaces were measured via contact-angle measurements and compression
      tests, respectively. Scanning electron microscopy (SEM) and fluorescent staining
      were used to observe the proliferation and morphology of chondrocyte cells on
      noncrosslinked and crosslinked surfaces. The crosslinked chitosan was found to be
      nontoxic to chondrocytes and more hydrophilic. Its compression modulus and
      stiffness increased, which may improve the scaffold resistance to wear and in
      vivo shrinkage once implanted. The increased stiffness also seemed to serve as an
      additional mechanical stimulus to promote chondrocyte growth and proliferation.
      The cell morphology on crosslinked scaffolds seen by SEM and fluorescent stain
      was the typical chondrocytic rounded shape. The method proposed provides a
      nontoxic way to increase the mechanical strength of the chitosan scaffolds.

PMID- 16110497
TI  - Poly(lactide)-poly(ethylene glycol) micelles as a carrier for griseofulvin.
AB  - In this work, the feasibility to develop micelle carriers of griseofulvin based
      on PLA-PEG copolymers was investigated. With the use of the dialysis method of
      micelle formation, the micellization behavior of a range of PLA(X)-PEG(5)
      copolymers was investigated. At copolymer concentrations in the organic solvent
      10-20 mg/mL, stable micelles with 100% yield could only be prepared from PLA(X)
      PEG(5) copolymers with molar composition in the range 50-70% PEG. The copolymers
      exhibited sufficiently low CMC to provide stable micelles in vivo. The loading
      capacity of PLA(4)-PEG(5) micelles with griseofulvin was 6.5 mg of drug/1 g of
      copolymer. The release of griseofulvin from the PLA-PEG micelles in vitro in
      phosphate-buffered saline (PBS) was sustained over 30 days. No burst effect was
      observed. Analysis of the release kinetics suggested that the release was erosion
      controlled. The release profile was biphasic. Micelle degradation data in PBS
      indicated that the second phase of release was induced by copolymer degradation.
      The PLA-PEG micelles of griseofulvin were stable in simulated gastric and
      intestinal fluids for a long-enough time for oral application. Overall, the PLA
      PEG micelles have suitable properties to be considered as potential oral or
      topical formulations of griseofulvin, provided that the drug-loading capacity of
      the micelles is sufficiently improved.

PMID- 16110499
TI  - Deletion at chromosome band 20p12.1 in colorectal cancer revealed by high
      resolution array comparative genomic hybridization.
AB  - Array comparative genomic hybridization (Array CGH) with tiling path resolution
      for a approximately 4.61 Mb region of chromosome band 20p12.1 has been used to
      investigate copy number loss in 48 colorectal cancer cell lines and 37 primary
      colorectal cancers. A recurrent deletion was detected in 55% of cell lines and
      23% of primary cancers and the consensus minimum region of loss was identified as
      a approximately 190 kb section from 14.85 Mb to 15.04 Mb of chromosome 20. Two
      noncoding RNA genes located in the region, BA318C17.1 and DJ974N19.1, were
      investigated by mutation analysis and real-time PCR in colorectal cancer cell
      lines. Sequence changes in BA318C17.1 and reduced expression of both genes was
      detected, suggesting that the abrogation of these genes may play a role in
      colorectal tumorigenesis.

PMID- 16110498
TI  - Etoposide, vincristine, and cyclosporin A with standard-dose radiation therapy in
      newly diagnosed diffuse intrinsic brainstem gliomas: a pediatric oncology group
      phase I study.
AB  - BACKGROUND: Brainstem gliomas (BSGs) are resistant to all therapy. Based on their
      imaging characteristics, we postulated that inhibition of P-glycoprotein (P-gp)
      associated with endothelial cells of the blood-brain barrier might enhance
      penetration of xenobiotic antineoplastics. PROCEDURE: Seven patients were
      enrolled in a Phase I study of etoposide, continuous infusion cyclosporine A
      given with and escalating doses of vincristine and concomitant standard-dose
      irradiation. RESULTS: Six patients were entered at the first level and one at the
      second. Closure of the study was mandated by dose-limiting neurotoxicity,
      consisting of seizures associated with white-matter changes, and alteration of
      consciousness with bulbar signs. One patient had tumor necrosis at 6 weeks,
      suggesting some tumor effect. Median survival for the group was 11 months, and
      for the patients who completed more than 1 month of therapy it was 11 months.
      CONCLUSION: This regimen proved excessively toxic.

PMID- 16110500
TI  - Novel amplicons on the short arm of chromosome 7 identified using high resolution
      array CGH contain over expressed genes in addition to EGFR in glioblastoma
      multiforme.
AB  - Amplification of a defined chromosome segment on the short arm of chromosome 7
      has frequently been reported in glioblastoma multiforme (GBM), where it is
      generally assumed that it is the result of over expression of the epidermal
      growth factor receptor (EGFR) gene that provides the selective pressure to
      maintain the amplification event. We have used high resolution array comparative
      genomic hybridization (aCGH) to analyze amplification events on chromosome 7p in
      GBM, which demonstrates that, in fact, several other regions distinct from EGFR
      can be amplified. To determine the changes in gene expression levels associated
      with these amplification events, we used oligonucleotide expression arrays to
      investigate which of the genes in the amplified regions were also over expressed.
      These analyses demonstrated that not all genes in the amplicons showed increased
      expression, and we have defined a series of over expressed genes on 7p that could
      potentially contribute to the development of the malignant phenotype in these
      tumors. The global analysis of amplification afforded by aCGH analysis has
      improved our ability to define numerical chromosome abnormalities in cancer cells
      and has raised the possibility that genes other than EGFR may be important.

PMID- 16110501
TI  - Neuropilin-1a is involved in trunk motor axon outgrowth in embryonic zebrafish.
AB  - Neuropilin-1, a receptor for axon-repellent semaphorins and vascular endothelial
      growth factor (VEGF), functions both in angiogenesis and axon growth. Here, we
      show strong expression of neuropilin-1a in primary motor neurons in the trunk of
      embryonic zebrafish. Reducing the expression of neuropilin-1a using antisense
      morpholino oligonucleotides induced aberrant branching of motor nerves,
      additional exit points of motor nerves from the spinal cord, and migration of
      neurons out of the spinal cord along the motor axon pathway in a dose-dependent
      manner. These phenotypes could be partially rescued by co-injecting neuropilin-1a
      mRNA. Other axons in the spinal cord and head appeared unaffected by the
      morpholino treatment. In addition, neuropilin-1a morpholino treatment disturbed
      normal formation of blood vessels in the trunk of 24 hours postfertilization
      embryos, as shown by microangiography. Morpholinos to VEGF also disturbed
      formation of blood vessels but did not affect motor axons, indicating that
      correct formation of blood vessels is not needed for the growth of primary motor
      axons. Morpholinos to the semaphorin 3A homologs semaphorin 3A1 and semaphorin
      3A2 also had no effect on motor axon growth. However, combined injections of
      neuropilin-1a morpholino, at a concentration that did not elicit axonal
      aberrations when injected alone, with VEGF, semaphorin 3A1, or semaphorin 3A2
      morpholinos synergistically increased the proportion of embryos showing aberrant
      motor axon growth. Thus, neuropilin-1a in primary motor neurons may integrate
      signals from several ligands and is needed for proper segmental growth of primary
      motor nerves in zebrafish.

PMID- 16110502
TI  - Mercury (II) alters mitochondrial activity of monocytes at sublethal doses via
      oxidative stress mechanisms.
AB  - The perennial controversy about the safety of mercury in dental amalgams has
      adversely affected the availability and the quality of dental care. Chronic
      Hg(II) blood concentrations above 300 nM are known to alter function of the
      nervous system and the kidney. However, the effects of blood concentrations of 10
      to 75 nM, far more common in the general population, are not clear and mechanisms
      of any effects are not known. The monocyte is an important potential target of
      Hg(II) because of its critical role in directing inflammatory and immune
      responses. In the current study we tested the hypothesis that concentrations of
      Hg(II) of 10 to 300 nM alter monocyte activity via a redox-dependent mechanism.
      Mitochondrial activity was used to establish inhibitory concentrations of Hg(II)
      following 6 to 72 h of exposures to THP1 human monocytic cells. Then
      subinhibitory concentrations were applied, and total glutathione levels and
      reactive oxygen species (ROS) were measured. Antioxidants [N-acetyl cysteine,
      (NAC); Na2SeO3, (Se)] and a pro-oxidant (tert-butylhydroquinone, tBHQ) were used
      to support the hypothesis that Hg(II) effects were redox-mediated. After 72 h of
      exposure, 20 microM of Hg(II) inhibited monocytic mitochondrial activity by 50%.
      NAC mitigated Hg(II)-induced mitochondrial suppression only at concentrations of
      greater than 10 microM, but Se had few effects on Hg-induced mitochondrial
      responses. tBHQ significantly enhanced mitochondrial suppression at higher Hg(II)
      concentrations. Hg(II) concentrations of 75 and 300 nM (0.075 and 0.30 microM,
      respectively) significantly increased total glutathione levels, and NAC mitigated
      these increases. Se plus Hg(II) significantly elevated Hg-induced total cellular
      glutathione levels. Increased ROS levels were not detected in monocytes exposed
      to mercury. Hg(II) acts in monocytic cells, at least in part, through redox
      mediated mechanisms at concentrations below those commonly associated with
      chronic mercury toxicity, but commonly occurring in the blood of some dental
      patients.

PMID- 16110503
TI  - MCT-4, A511/Basigin and EF5 expression patterns during early chick
      cardiomyogenesis indicate cardiac cell differentiation occurs in a hypoxic
      environment.
AB  - We have identified the presence of the hypoxia marker EF5 in the stage 4/5 chick
      heart fields. This suggests that cardiac cell differentiation occurs in a
      relatively anaerobic environment. Monocarboxylate transporter (MCT) studies in
      adult cardiac myocytes have demonstrated that MCTs catalyze proton-linked
      pyruvate and lactate transport activity. 5A11/Basigin is an ancillary protein
      that targets MCTs to the plasma membrane for their function. MCT-4 expression is
      most evident in cells with a high glycolytic rate associated with hypoxic energy
      production. Subsequent to the immunohistochemical localization of EF5 in the
      early heart field, we continued in our analysis during stages 5 to 12 for the
      expression of indicators of cellular glycolytic metabolism in the developing
      heart, such as MCT-4, MCT-1, and 5A11 (Basigin/CD147). Our observations indicate
      that MCT-4 and 5A11/Basigin are expressed early, in a differential left-right
      pattern, in the bi-lateral plate mesoderm, as the cardiac compartment is forming.
      At stage 11, MCT-4/5A11 continues to be highly expressed in the myocardial wall
      of the looping heart, but not in the dorsal mesocardium. RT-PCR analyses for MCT
      1, -4, and 5A11 indicate that MCT-4 and 5A11 are expressed throughout precardiac,
      embryonic, and fetal stages in the heart. MCT-1 is first detected in the heart on
      embryonic day 3 and then remains expressed throughout development to hatching.
      These results indicate that cardiac precursor cells are equipped for
      differentiating in a hypoxic environment using anaerobic metabolism for energy
      production.

PMID- 16110504
TI  - Pigment cell distributions in different tissues of the zebrafish, with special
      reference to the striped pigment pattern.
AB  - The orderly pigment pattern of zebrafish (Danio rerio) is a good model system for
      studying how spatial patterns form in animals. Recent molecular genetic studies
      have shown that interactions between the pigment cells play major roles in
      pattern formation. In the present study, we performed comparative transmission
      electron microscopy of pigment cells, in order to clarify the structural
      interactions of pigment cells in tissues with and without a striped pattern. In
      patterned tissues, pigment cells were distributed as a one-cell-thick sheet. The
      layer order of the sheets is always kept strictly. In tissues without a striped
      pattern, the layer order was often disturbed or the cells were distributed in a
      scattered, double-sheeted, or an accumulated pile. Our observations suggest that
      the underlying mechanism that controls the vertical order of the pigment cells is
      related to that controlling the stripe pattern.

PMID- 16110505
TI  - Bone morphogenetic protein signaling pathway plays multiple roles during
      gastrointestinal tract development.
AB  - The bone morphogenetic protein (BMP) signaling pathway plays an essential role
      during gastrointestinal (GI) tract development in vertebrates. In the present
      study, we use an antibody that recognizes the phosphorylated and activated form
      of Smad1, 5, and 8 to examine (by immunohistochemistry) the endogenous patterns
      of BMP signaling pathway activation in the developing GI tract. We show that the
      endogenous BMP signaling pathway is activated in the mesoderm, the endoderm, and
      the enteric nervous system (ENS) of the developing chick GI tract and is more
      widespread than BMP ligand expression patterns. Using an avian-specific
      retroviral misexpression technique to activate or inhibit BMP signaling pathway
      activity in the mesoderm of the gut, we show that BMP activity is required for
      the pattern, the development, and the differentiation of all three tissue types
      of the gut: mesoderm (that forms the visceral smooth muscle), endoderm (that
      forms the epithelium), and ectoderm (that forms the ENS). These results
      demonstrate that BMP signaling is activated in all the tissue layers of the GI
      tract during the development and plays a role during interactions and reciprocal
      communications of these tissue layers.

PMID- 16110506
TI  - Transposon tools and methods in zebrafish.
AB  - Zebrafish is an excellent model animal to study vertebrate development by genetic
      approaches. Hundreds of mutations affecting various processes of development have
      been isolated by chemical mutagenesis and insertional mutagenesis using a
      pseudotyped retrovirus. However, useful transposon tools and methods had not been
      available in zebrafish. This is mainly because no active transposable element has
      been found from the zebrafish genome. Recently, efficient transgenesis, gene
      trap, and enhancer trap methods have been developed in zebrafish by using the
      Tol2 and the Sleeping Beauty transposon systems. These methods should increase
      the usefulness of zebrafish as a model vertebrate and facilitate the study of
      developmental biology, genetics, and genomics.

PMID- 16110508
TI  - Osteoporosis and rate of bone loss among postmenopausal survivors of breast
      cancer.
AB  - BACKGROUND: Breast cancer diagnosis and treatment may put women at higher risk
      for osteoporosis in later life. METHODS: In a subgroup of participants in the
      Women's Health Initiative Observational Study, authors of the current study
      investigated differences in bone mineral density (BMD, measured by dual-energy x
      ray absorptiometry) between breast cancer survivors (n = 209) and a noncancer
      reference group (n = 5759). RESULTS: In comparison to the reference group, breast
      cancer survivors had significantly lower total body BMD value (0.989 vs. 1.013
      g/cm(2), P = 0.001) and total hip BMD value (0.823 vs. 0.845 g/cm(2), P = 0.02)
      at baseline after adjustment for age, race/ethnicity, years since menopause, and
      clinical center. These lower BMD levels were largely explained by lower usage of
      hormone therapy (HT) among survivors: after additional statistical adjustment for
      HT, hip BMD values were 0.834 versus 0.844 g/cm(2) (P = 0.26), and total body
      values were 1.005 versus 1.013 g/cm(2) (P = 0.33) for survivors and reference
      women, respectively. More than 77% of survivors with osteoporosis were
      undiagnosed by their healthcare providers, and this was similar to the
      undiagnosed rate in the reference group (85.7%). Longitudinally, breast cancer
      survivors in this study did not demonstrate an accelerated rate of bone loss
      compared with the reference population. CONCLUSIONS: Associated with lower HT
      usage, postmenopausal survivors of breast cancer were more likely to have low BMD
      in comparison to other women of the same age; and many of these survivors with
      osteoporosis were undiagnosed.

PMID- 16110509
TI  - On some lung function analyses.

PMID- 16110511
TI  - Quantum dots are powerful multipurpose vital labeling agents in zebrafish
      embryos.
AB  - Recently, inorganic fluorescent contrast agents composed of semiconductor
      materials have been introduced to biological imaging approaches. These so-called
      quantum dots provide unique and promising properties unreached by organic
      fluorophores, but their use as contrast agents within live organisms has been
      limited, probably due in part to concerns about their in vivo tolerance. Using
      transparent zebrafish embryos, we challenged quantum dots with a series of
      intravital imaging problems. We show that quantum dots provide a high fluorescent
      yield within targeted tissues, possess immense photostability, can be targeted to
      specific subcellular compartments, remain within targeted cells as lineage
      tracers, are easily separable from conventional organic fluorescent dyes, and are
      fixable, allowing them to be used in combination with immunohistochemistry after
      live recordings. Thus, quantum dots combine the specific advantages of different
      organic fluorescent contrast agents and promise to become the first fluorophore
      feasible for long-lasting intravital time-lapse studies. Finally, we show by co
      labeling blood vessels of the vasculature and major axon tracts of the nervous
      system that, for establishing these networks, the same guidance cues might be
      used in some body parts, whereas in others, both networks appear to develop
      independently from one another. Thus, the bright fluorescence of quantum dots
      will help to unravel many open questions in the fields of embryology, cell
      biology, as well as phenotyping and disease diagnosis.

PMID- 16110512
TI  - vHnf1 regulates specification of caudal rhombomere identity in the chick
      hindbrain.
AB  - The homeobox-containing gene variant hepatocyte nuclear factor-1 (vHnf1) has
      recently been shown to be involved in zebrafish caudal hindbrain specification,
      notably in the activation of MafB and Kro x 20 expression. We have explored this
      regulatory network in the chick by in ovo electroporation in the neural tube. We
      show that mis-expression of vHnf1 confers caudal identity to more anterior
      regions of the hindbrain. Ectopic expression of mvHnf1 leads to ectopic
      activation of MafB and Kro x 20, and downregulation of Hoxb1 in rhombomere 4.
      Unexpectedly, mvhnf1 strongly upregulates Fgf3 expression throughout the
      hindbrain, in both a cell-autonomous and a non-cell-autonomous manner. Blockade
      of FGF signaling correlates with a selective loss of MafB and Kro x 20
      expression, without affecting the expression of vHnf1, Fgf3, or Hoxb1. Based on
      these observations, we propose that in chick, as in zebrafish, vHnf1 acts with
      FGF to promote caudal hindbrain identity by activating MafB and Kro x 20
      expression. However, our data suggest differences in the vHnf1 downstream cascade
      in different vertebrates.

PMID- 16110510
TI  - Challenges in the study of neuronal differentiation: a view from the embryonic
      eye.
AB  - Progress in the study of the molecular mechanisms that regulate neuronal
      differentiation has been quite impressive in recent years, and promises to
      continue to an equally fast pace. This should not lead us into a sense of
      complacency, however, because there are still significant barriers that cannot be
      overcome by simply conducting the same type of experiments that we have been
      performing thus far. This article will describe some of these challenges, while
      highlighting the conceptual and methodological breakthroughs that will be
      necessary to overcome them.

PMID- 16110513
TI  - Tenascin-C is involved in motor axon outgrowth in the trunk of developing
      zebrafish.
AB  - Motor axons in the trunk of the developing zebrafish exit from the ventral spinal
      cord in one ventral root per hemisegment and grow on a common path toward the
      region of the horizontal myoseptum, where they select their specific pathways.
      Tenascin-C, a component of the extracellular matrix, is concentrated in this
      choice region. Adaxial cells and other myotomal cells express tenascin-C mRNA,
      suggesting that these cells are the source of tenascin-C protein. Overexpressing
      an axon repellent fragment containing the cysteine-rich region and the epidermal
      growth factor-like repeats of tenascin-C led to retarded growth of ventral motor
      nerves between their spinal exit point and the horizontal myoseptum. Injection of
      a protein fragment containing the same part of tenascin-C also induced slower
      growth of motor nerves. Conversely, knock down of tenascin-C protein resulted in
      abnormal lateral branching of ventral motor nerves. In the zebrafish unplugged
      mutant, in which axons display pathfinding defects in the region of the
      horizontal myoseptum, tenascin-C immunoreactivity was not detectable in this
      region, indicating an abnormal extracellular matrix in unplugged. We conclude
      that tenascin-C is part of a specialized extracellular matrix in the region of
      the horizontal myoseptum that influences the growth of motor axons.

PMID- 16110514
TI  - The effect of equilibration time on survival and development rates of mouse
      pronuclear-stage embryos vitrified in solid surface (SSV) and convential straws:
      in vitro and in vivo evaluations.
AB  - The objective of this study was to improve the efficiency of cryopreservation of
      pronuclear-stage (PN) mouse embryos. A novel vitrification technique (solid
      surface vitrification, SSV) was compared with a convential one in straws both for
      cryosurvival and obtaining progeny from cryopreserved PN mouse embryos. In the
      SSV method, 15-20 PN embryos were exposed to vitrification solutions for
      approximately 20 sec after equilibration, and then they were dropped in 2 microl
      drops onto a pre-cooled (-150 to -180 degrees C) metal surface. In the straws
      method, groups of 5-10 PN embryos were loaded in a single straw after
      equilibration. In experiment I, it was compared the effect of the vitrification
      solutions alone, without vitrification. No reduction was detected in survival,
      cleavage and blastocysts rates and the lowest development rate was obtained from
      hatched blastocyst for 20 min equilibration (24.5%). In experiment II, SSV method
      resulted in significantly higher survival and cleavage rates than that of in
      straw vitrified 15-20 min group (87% vs. 60%, 83% vs. 67%, respectively; P <
      0.05). There were no statistical differences among any of the blastocyts groups.
      However, there was a statistical difference in hatched blastocysts between 15 to
      5, 10, and 20 min (P < 0.05). In experiment III, it was found no major effect
      among equilibration time periods in toxicity groups according to the mean cell
      number of blastocysts developed from PN embryos. But, there was a significant
      differences between 15 min SSV and 10 min in straw vitrified according to the
      mean cell number of blastocysts developed from PN embryos following vitrification
      (P < 0.05). The good results were obtained from 15 min equilibration group for
      SSV and 10 min equilibration group for straw vitrification. In the last
      experiment, embryo transfer after vitrification and toxicity was investigated.
      There were significant differences between SSV and straw just on the rate of pups
      born (30% and 20.5% respectively; P < 0.05). In conclusion, vitrification of PN
      mouse embryos by SSV can result in high rates of in vitro development to expanded
      and hatched blastocyst stage and in vivo development to live pups.

PMID- 16110515
TI  - Sexual dimorphism in metapodial and phalanges length ratios in the wood mouse.
AB  - Relative length of metapodials and digits is sexually dimorphic in most primates
      and one rodent and one bird species studied so far. Recently, interest in digit
      ratios has increased because of their correlation with diverse physiological,
      psychological, and performance traits in humans. These correlations may reflect
      the effect of androgens during early ontogeny on digit development and their long
      term organizational effects on extragenital organs. Inter- and intrasexual
      variation in digit ratios may be ultimately controlled by modulation of the
      expression of Hoxa and Hoxd genes. Since Hox genes are conserved in vertebrates,
      similar patterns of sex-related variation in length ratios may be expected across
      taxa. In fact, sexual dimorphism in length ratios has been documented for
      metapodials or digit bones in nonhuman vertebrates, but the specific pattern of
      sex-related variation varies considerably. However, no study has investigated
      sexual dimorphism in length ratios between all ray segments (metapodials plus
      phalanges) using osteometrical measures. In an outbred wild population of wood
      mice (Apodemus sylvaticus), we found extensive sex-related variation in ratios
      between osteometrical length of the phalanges, but not metatarsals, similar to
      that recorded on undissected digits of humans and laboratory mice. Most sexually
      dimorphic ratios involved the second digit. We found very weak evidence for
      directional asymmetry in length ratios. The present study shows that sex-related
      variation in length ratios between digit segments observed in mammals may
      actually depend on relative bone length. Hence, other species may be used to
      investigate the causal and semeiotic implications of variation in human digit
      ratios.

PMID- 16110517
TI  - Virtual-move parallel tempering.

PMID- 16110516
TI  - Development of the articular cavity in the rat temporomandibular joint with
      special reference to the behavior of endothelial cells and macrophages.
AB  - Previous developmental studies on the temporomandibular joint (TMJ) have proposed
      several hypotheses on the formation of its articular cavity. However, detailed
      information is meager. The present study examined the formation process of the
      articular cavity in the rat TMJ by immunocytochemistry for CD31, RECA-1, and ED1,
      which are useful cellular markers for endothelial cells and monocyte/macrophage
      lineages, respectively. The upper articular cavity formation had begun by
      embryonic day 21 (E21) and was completed at postnatal day 1 (P1) in advance of
      the lower cavitation; the latter took place from P1 to P3. The occurrence and
      distribution pattern of the CD31-, RECA-1-, and ED1-positive cells differed
      between the upper and lower articular cavity-forming areas: the ED1-positive
      cells exclusively occurred in the area of the prospective upper articular cavity
      prior to its formation, while no ED1-positive cell appeared in the lower cavity
      forming area. In contrast, the CD31- and RECA-1-positive endothelial cells were
      restricted to the lower cavity-forming area (never the prospective upper cavity)
      at E19 and diminished thereafter. Throughout the cavity formation, we failed to
      find any apoptotic cells in the cavity formation area, indicating no involvement
      of apoptosis in the cavity formation in TMJ. The present findings on the
      behaviors of endothelial cells and ED1-positive cells show a possibility of
      different mechanism in the cavity formation between the upper and lower articular
      cavities in the rat TMJ. The appearance of ED1-reactive cells and temporal
      vascularization may play crucial roles in the upper and lower articular cavity
      formation, respectively.

PMID- 16110518
TI  - Structure, protonation state and dynamics of catalase compound II.
AB  - Density functional calculations are performed to investigate the protonation
      state of the compound II intermediate (Cpd II) of the catalase reaction cycle.
      Several scenarios are considered, depending on the protonation state of the
      active center (heme) and the catalytic His residue. Only the form with a
      protonated Fe==O unit (i.e. Fe--OH) is in agreement with the recent high
      resolution crystal structure, while the traditional description of Cpd II as an
      oxoferryl species corresponds to a configuration slightly higher in energy. The
      computed Fe--O stretch frequency is in agreement with the available experimental
      data. Molecular dynamics simulations show that the pocket water remains in the
      region between the His61 and Asn133 catalytic residues, but it occasionally tries
      to escape towards the main channel in a concerted motion with the Asn133 residue.
      A possible role for this residue in the process of ligand entry/escape from the
      binding pocket is proposed.

PMID- 16110519
TI  - Solvent and protein effects on the structure and dynamics of the rhodopsin
      chromophore.
AB  - The structure and dynamics of the retinal chromophore of rhodopsin are
      investigated systematically in different environments (vacuum, methanol solution,
      and protein binding pocket) and with different computational approaches
      (classical, quantum, and hybrid quantum mechanics/molecular mechanics (QM/MM)
      descriptions). Finite temperature effects are taken into account by molecular
      dynamics simulations. The different components that determine the structure and
      dynamics of the chromophore in the protein are dissected, both in the dark state
      and in the early photointermediates. In vacuum and in solution the chromophore
      displays a very high flexibility, which is significantly reduced by the protein
      environment. In the 11-cis chromophore, the bond-length alternation, which is
      correlated with the dipole moment, is found to be similar in solution and in the
      protein, while it differs greatly with respect to minimum-energy vacuum
      structures. In the model of the earliest protein photointermediate, the highly
      twisted chromophore shows a very reduced bond-length alternation.

PMID- 16110520
TI  - The chemistry of wine polyphenolic C-glycosidic ellagitannins targeting human
      topoisomerase II.
AB  - Polyphenolic nonahydroxyterphenoyl-containing C-glycosidic oak ellagitannins are
      found in wine as a result of the aging of this beverage in oak-made barrels. Once
      in the slightly acidic wine (pH approximately 3-4), some of these complex natural
      products such as (-)-vescalagin (1), but not its C-1 epimer (-)-castalagin (2),
      can capture grape-derived nucleophilic entities such as ethanol, the flavanols
      catechin (10a) and epicatechin (10b), the anthocyanin oenin (13b), and the
      thiolic glutathione (16) to furnish condensation products with retention of
      configuration at the C-1 locus. A computer-aided rationale of this high
      diastereoselectivity is given. These condensation products can contribute to the
      modulation of organoleptic properties of the wine, as evidenced by the 23 nm
      bathochromic shift color absorbance observed with the novel oenin-based
      anthocyano-ellagitannin (15b). Hydrolysis of 1 under solvolytic conditions
      furnished another novel compound that we refer to as vescalene (21), in addition
      to the known (-)-vescalin (18). Of pharmacological importance is the fact that
      most of these found-in-wine water-soluble ellagitannin derivatives are much more
      potent than etoposide (VP-16) at inhibiting top2-mediated DNA decatenation in
      vitro (top2=topoisomerase II)). The known (-)-vescalin (18) and the novel
      vescalene (21) fully inhibited top2 at 10 microM concentration!

PMID- 16110521
TI  - Domino 6pi-electrocyclization/Diels-Alder reactions on 1,6-disubstituted (E,Z,E)
      1,3,5-hexatrienes: versatile access to highly substituted tri- and tetracyclic
      systems.
AB  - The (E,Z,E)-1,3,5-hexatrienes 1a, 2a,b and 3b undergo 6pi-electrocyclization
      within 15-30 min upon heating to 200-215 degrees C. While the cyclohexene
      annelated products 8a,b were stable, the analogous cyclopentene- and cycloheptene
      annelated derivatives 7a and 9b easily underwent dehydrogenation to the
      corresponding aromatic compounds 10a and 12b during the work-up. The
      cyclohexadiene derivatives 8a,b were employed in thermal Diels-Alder reactions
      with 4-phenyl-3H-1,2,4-triazoline-3,5-dione (PTAD) and tetracyanoethylene (TCNE)
      to give the expected [4+2] cycloadducts 13a and 14a in good yields (60 and 78%).
      The initially formed cycloadduct of 8a and dimethyl acetylenedicarboxylate (DMAD)
      underwent a subsequent retro-Diels-Alder reaction to give the
      tetrahydronaphthalene 11b (47%). Under high pressure (10 kbar), the cycloadduct
      15a was formed at room temperature and could be isolated in 44% yield. TCNE and N
      phenylmaleimide with 8a under high pressure also led to the [4+2] cycloadducts
      14a and 16a in good yields (60 and 77%). The 6pi-electrocyclization and
      subsequent Diels-Alder reaction, when performed as a one-pot domino process,
      provided direct access to Diels-Alder products of intermediately formed 6pi
      electrocyclization products, for example from the 1,3,5-hexatrienes 1a,b, 2a,b,
      3b and TCNE to the corresponding tricyclic products 17a,b, 14a,b, 18b in moderate
      to good yields (27-80%) depending on the nature of the alkoxycarbonyl group. Such
      sequential reactions with N-phenylmaleimide, maleic anhydride, dimethyl maleate
      and fumarodinitrile, the latter two under high pressure (10 kbar), worked as well
      to yield 16b (70%), 19a,b (19, 32%) and 20b (39%) and 21b (76%), respectively.
      With PTAD, however, the hexatrienes 2a,b reacted at ambient temperature without
      6pi-electrocyclization to give the formal [4+2] cycloadducts 27a,b (48 and 46%),
      most probably via zwitterionic intermediates 23a,b and 25a,b.

PMID- 16110522
TI  - The effect of the PPARgamma ligand rosiglitazone on energy balance regulation.
AB  - BACKGROUND AND AIM: Fat mass generation requires an energy surplus and the
      activity of the peroxisome proliferator-activated receptor gamma (PPARgamma). We
      investigated if the PPARgamma ligand rosiglitazone influences substrate usage,
      energy expenditure (EE) and energy intake (EI) and, thereby, how PPARgamma
      activity contributes to susceptibility to obesity. METHODS: Twenty healthy males
      (20-29 years) were randomly assigned to receive a placebo (n = 10) or
      rosiglitazone (8 mg/d) (n = 10) for seven consecutive days, while staying in a
      respiration chamber. Food intake was ad libitum. Body composition was determined
      by underwater weighing (day 1) and deuterium dilution (day 1 and 8). RESULTS:
      Mean (+/-SE) EI was 15.9 +/- 0.9 MJ/d in the placebo group and 18.9 +/- 1.2 MJ/d
      in the rosiglitazone group. Mean EE was 11.3 +/- 0.3 MJ/d and 12.5 +/- 0.5 MJ/d
      for the placebo and rosiglitazone groups respectively. This resulted in a
      cumulative positive energy balance (EB) of 32.3 +/- 5.1 MJ for placebo and 44.7
      +/- 6.9 MJ for rosiglitazone. There were no significant differences in EI, EE,
      and EB between treatments. Both groups did not adjust their fat oxidation to the
      increased fat intake, but fat oxidation decreased faster in the rosiglitazone
      group (significantly lower on days 6 and 7). During treatment with rosiglitazone,
      significantly more fat storage was seen in overweight subjects while this was not
      the case in the placebo group. CONCLUSIONS: Our results suggest a shift in
      substrate usage during PPARgamma stimulation leading to a preference for fat
      storage, especially in subjects with a higher BMI.

PMID- 16110523
TI  - AIDS activists decry steady hikes in HIV drug prices.

PMID- 16110524
TI  - Exposure. Man pleads guilty to exposing others to HIV.

PMID- 16110525
TI  - First lady promotes Africa's HIV/AIDS prevention program.

PMID- 16110526
TI  - AIDS threat. Biting shoplifter gets five years after HIV threat.

PMID- 16110527
TI  - AIDS depression fails as defense for drug possession.

PMID- 16110528
TI  - HIV as weapon. Court upholds man's enhanced sentence for HIV exposure.

PMID- 16110530
TI  - For the patient. Kidney disease increases for populations around the world: it's
      time to take action.

PMID- 16110529
TI  - Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate
      haem synthesis.
AB  - Iron is required to produce haem and iron-sulphur (Fe-S) clusters, processes
      thought to occur independently. Here we show that the hypochromic anaemia in
      shiraz (sir) zebrafish mutants is caused by deficiency of glutaredoxin 5 (grx5),
      a gene required in yeast for Fe-S cluster assembly. We found that grx5 was
      expressed in erythroid cells of zebrafish and mice. Zebrafish grx5 rescued the
      assembly of grx5 yeast Fe-S, showing that the biochemical function of grx5 is
      evolutionarily conserved. In contrast to yeast, vertebrates use iron regulatory
      protein 1 (IRP1) to sense intracellular iron and regulate mRNA stability or the
      translation of iron metabolism genes. We found that loss of Fe-S cluster assembly
      in sir animals activated IRP1 and blocked haem biosynthesis catalysed by
      aminolaevulinate synthase 2 (ALAS2). Overexpression of ALAS2 RNA without the 5'
      iron response element that binds IRP1 rescued sir embryos, whereas overexpression
      of ALAS2 including the iron response element did not. Further, antisense
      knockdown of IRP1 restored sir embryo haemoglobin synthesis. These findings
      uncover a connection between haem biosynthesis and Fe-S clusters, indicating that
      haemoglobin production in the differentiating red cell is regulated through Fe-S
      cluster assembly.

PMID- 16110531
TI  - For the patient. Does religion make a difference to a person's health?

PMID- 16110533
TI  - The more things change...

PMID- 16110532
TI  - Tau protein aggregation in the frontal and entorhinal cortices as a function of
      aging.
AB  - OBJECTIVES: The abnormal accumulation of tau protein is increasingly recognized
      as the neuropathological hallmark of a number of dementing illness in which
      frontotemporal lobar degeneration occurs. In this paper we examined the age
      dependant deposition of tau protein in the frontal and entorhinal neocortices.
      METHODS: We examined autopsy records from 1997 to 2002 and selected 87 cases (10
      in each decade from 0 to 79 years of age, 7 in 80-89 decade) with no history of
      dementia or other neurodegenerative diseases, and for which neurodegenerative
      diseases were excluded neuropathologically. Archival paraffin-embedded frontal
      and entorhinal cortices were examined by both Gallyas-Braak silver staining and a
      panel of antibodies recognizing tau protein accumulation. RESULTS: Tau neuronal
      aggregates were observed in both frontal and entorhinal cortices in the third
      decade. While the frontal neuronal tau aggregates remained infrequent in the
      remaining decades, the number and extent ofneuronal tau aggregates in the
      entorhinal cortex increased such that by the 7th decade the majority of cases
      showed extensive tau aggregate formation. The most consistent morphological
      observation was of dense, perikaryal neuronal tau-immunoreactive aggregates,
      similar to the total tau distribution, firstly presenting in cortical layers II
      and III and subsequently involving in layers IV-VI. Neuropil threads became
      maximal in the 9th decade in both frontal and entorhinal cortices. Astrocytic tau
      accumulation was first observed in both frontal and entorhinal cortices in the
      6th decade, predominantly in layer I and subcortical white matter, and increased
      in number with aging. Extraneuronal tau reactive aggregates and coiled bodies
      were rarely observed in the entorhinal cortex, and when present, were scattered
      through layer II to VI. CONCLUSIONS: We have observed an age-dependant pattern of
      neuronal, extraneuronal and glial tau protein accumulation in the entorhinal
      cortex in individuals without neurodegenerative diseases. In contrast, tau
      protein aggregation is infrequently observed in the frontal cortex as a function
      of aging.

PMID- 16110534
TI  - IAPAC-AFRO, Southern African HIV Clinicians Society sign MOU for broad-reaching
      partnership in Africa.

PMID- 16110535
TI  - Can drugs catch up with HIV? 12th Conference on Retroviruses and Opportunistic
      Infections. February 22-25, 2005, Boston.

PMID- 16110536
TI  - Sexual HCV transmission among HIV-negative gay men.

PMID- 16110537
TI  - Stopping HIV infection with PEP. U.S. guidelines for using established meds in an
      unproven way.

PMID- 16110538
TI  - True tales of prevention. A PEP worker speaks, plus a PEP diary.

PMID- 16110539
TI  - From condoms to needles and everything in between. Shades of gray with harm
      reduction.

PMID- 16110540
TI  - United States of harm reduction. The politics, the money, the health care, the
      future.

PMID- 16110541
TI  - The silver van. Talking to people in Chicago's Blood Alley.

PMID- 16110542
TI  - Sex, drugs and...harm reduction. Things to think about and things you can do.

PMID- 16110543
TI  - Living with[out] crystal meth. Addicts were "those" people, not me.

PMID- 16110544
TI  - Ordinary strangers. Mr. Clean, Lady Goodwill, and other folks at TPAN's needle
      exchange.

PMID- 16110545
TI  - HIV drug interactions in 2005.

PMID- 16110546
TI  - Minocycline shown to have protection for the brain against HIV. Results of a
      preclinical study recently published in JAMA.

PMID- 16110547
TI  - Reducing HIV infections at circuit parties.

PMID- 16110548
TI  - Crystal meth use worsens HIV-related brain damage.

PMID- 16110549
TI  - US approves new HBV drug.

PMID- 16110550
TI  - EuroSIDA cohort: 9% coinfected with HIV/HBV.

PMID- 16110552
TI  - Report from the National HIV Prevention Conference.

PMID- 16110551
TI  - Boehringer drug for resistant HIV approved.

PMID- 16110553
TI  - Generic drugs key to uphill AIDS fight.

PMID- 16110554
TI  - HIV and the breast.
AB  - HIV infection and antiretroviral therapy may alter the spectrum and frequency of
      diseases that affect the breast. The differential diagnosis of conditions of the
      breast that a practitioner may encounter in HIV-infected persons includes
      infection, morphologic alterations, and malignancy. Atypical infections may
      involve the breast as CD4+ T-cell counts wane. More commonly, HIV-infected
      persons present with gynecomastia, which may be caused by a variety of
      conditions, including exposure to HAART. True gynecomastia, resulting from
      proliferation of male breast ducts and periductal stroma, might be differentiated
      from lipomastia--a manifestation of lipodystrophy, characterized by the
      deposition of adipose tissue in the breast. In the era of HAART, HIV-infected
      patients with malignancy--particularly those who have robust CD4+ T-cell counts
      and well-controlled HIV viral loads--should be treated similarly to their HIV
      negative counterparts.

PMID- 16110555
TI  - Tenofovir and didanosine: a dangerous liaison.

PMID- 16110556
TI  - Kawasaki-like disease in an HIV-infected patient.

PMID- 16110557
TI  - Gynecologic care and family planning for HIV-infected women.
AB  - Owing to advances in the understanding and treatment of HIV infection, most
      persons infected with HIV are now living longer, healthier lives. With the
      dramatic reduction in mother-to-child transmission in the past decade, the
      outlook on life has changed for women with HIV infection. It is critical that a
      new strategic plan for prevention of HIV transmission and a proactive approach to
      reproductive health care be implemented by health care providers who care for
      these women. Promotion of risk reduction counseling, screening for sexually
      transmitted diseases and lower genital tract disease, assessment of options for
      birth control, and pre-conception counseling should be integral components of
      gynecologic health care for HIV-infected women. This article reviews the current
      status of gynecologic and reproductive health care for HIV-infected women.

PMID- 16110558
TI  - Adapting CDC DEBI list for target audiences is a major issue among CBOs.
      Translation changes can affect funding.
AB  - State and federal funding already was tight, and now it has become tighter for
      prevention work since most funding sources are requiring HIV organizations to
      follow strict guidelines regarding the use of evidence-based HIV prevention
      interventions. So far, the CDC has a list of 12 evidence-based interventions that
      include training materials for sites that desire to replicate them, but this
      limited list does not meet all of the target population needs. So behavior
      scientists say the interventions often need extensive adaptation, which is both
      expensive and difficult.

PMID- 16110559
TI  - DEBI list grows slowly as CBOs adapt models. CDC official explains process.
AB  - Community-base organizations and other that are looking for evidence-based HIV
      prevention interventions to use might be discouraged by how few are included on
      the DEBI list, but they should know that help is on the way.

PMID- 16110560
TI  - Meth's impact on HIV epidemic being studied. Drug's use is growing problem among
      MSMs.
AB  - The use of crystal methamphetamines doubles a person's risk for HIV infections,
      and there has been increasing awareness among public health officials that
      methamphetamine use is driving new HIV infections, especially among men who have
      sex with men, an expert says.

PMID- 16110561
TI  - Antidepressant treatment may improve adherence. Routine depression screening
      recommended.
AB  - While surveying long-term data of HIV-infected people, an investigator was struck
      by how commonly HIV patients were diagnosed with depression. This observation led
      to a study of depression and medication adherence among HIV-infected patients
      seen in urban health settings between 1997 and 2001.

PMID- 16110562
TI  - NYC study determines true HIV prevalence. Study puts number to untested,
      unreported.
AB  - Name-base reporting of HIV infection has been successful in New York City since
      it was begun in June 2000, but there still remain holes in the surveillance
      system in which thousands of HIV-infected individuals are lost, according to
      recent research.

PMID- 16110563
TI  - FDA notifications. FDA approves generic foscarnet sodium injection.

PMID- 16110564
TI  - FDA notifications. Pediatric HIV infection guidelines updated.

PMID- 16110565
TI  - FDA notifications. Roche issues letter about saquinavir.

PMID- 16110566
TI  - Methamphetamine, the brain, HIV, and mental health.

PMID- 16110567
TI  - Evidence-based treatments for methamphetamine abuse.

PMID- 16110568
TI  - An enterprising solution takes one step forward. Global plan for AIDS vaccines
      welcomed with endorsements and questions.

PMID- 16110569
TI  - Researchers take a measured response. Immunologists compare data and techniques
      at Measurement of Antigen-Specific Immune Response conference.

PMID- 16110570
TI  - Aches and pains. Learning lessons from the influenza vaccine shortage.

PMID- 16110571
TI  - NIH begins second Phase I clinical trial of HIV vaccine.

PMID- 16110572
TI  - Phase I trial of ADMVA vaccine begins in New York.

PMID- 16110573
TI  - Roundtable. Revisiting the role of single-dose nevirapine for preventing
      perinatal HIV transmission.

PMID- 16110574
TI  - Guideline watch. New guidelines on treating chronic hepatitis B and C in HIV
      coinfected patients.

PMID- 16110575
TI  - Effects of high pressure processing on infectivity of Toxoplasma gondii oocysts
      for mice.
AB  - High pressure processing (HPP) has been shown to be an effective non-thermal
      method of eliminating non-spore forming bacteria from a variety of food products.
      The shelf-life of the products is extended and the sensory features of the food
      are not or only minimally effected by HPP The present study examined the effects
      of HPP using a commercial scale unit on the viability of Toxoplasma gondii
      oocysts. Oocysts were exposed from 100 to 550 MPa for 1 min in the HPP unit and
      then HPP treated oocysts were orally fed to groups of mice. Oocysts treated with
      550 MPa or less did not develop structural alterations when viewed with light
      microscopy. Oocysts treated with 550 MPa, 480 MPa, 400 Mpa, or 340 MPa were
      rendered noninfectious for mice. Mice fed oocysts treated with no or 100 to 270
      MPa became infected and most developed acute toxoplasmosis and were killed or
      died 7 to 10 days after infection. These results suggest that HPP technology may
      be useful in the removal of T. gondii oocysts from food products.

PMID- 16110576
TI  - A man with periappendicular ulcerations.

PMID- 16110577
TI  - Prevention of psychosis.

PMID- 16110578
TI  - Trepid and intrepid travelers.

PMID- 16110579
TI  - Real-time polymerase chain reaction to diagnose lymphogranuloma venereum.

PMID- 16110580
TI  - SARS vaccine protective in mice.

PMID- 16110581
TI  - Echinococcosis, Ningxia, China.

PMID- 16110582
TI  - Mycobacterium neoaurum contamination.

PMID- 16110583
TI  - Yersinia pestis genotyping.

PMID- 16110584
TI  - What is a traumatic event?

PMID- 16110585
TI  - Pandemic Vibrio parahaemolyticus O3:K6, Europe.

PMID- 16110586
TI  - Q fever and the US military.

PMID- 16110587
TI  - Anaplasma phagocytophilum, Sardinia, Italy.

PMID- 16110588
TI  - Energy healing: an alternative explanation for efficacy attributed to massage
      therapy?

PMID- 16110589
TI  - Williamsia muralis pulmonary infection.

PMID- 16110590
TI  - Neisseria meningitidis endotoxin and capsule transmission by transplantation.

PMID- 16110591
TI  - Potentially preventable suicide.

PMID- 16110592
TI  - Transcranial direct current stimulation in developing countries.

PMID- 16110593
TI  - Economic evaluation in complementary and alternative medicine.

PMID- 16110594
TI  - Limitations of rapid tranquillisation trial.

PMID- 16110595
TI  - Drug combinations for rapid tranquillisation.

PMID- 16110596
TI  - On: confidentiality with respect to third parties.

PMID- 16110597
TI  - On: metaphor and the violent act.

PMID- 16110598
TI  - Surveillance of human calicivirus in Spain.

PMID- 16110599
TI  - Monitoring health care workers after smallpox vaccination: findings from the
      Hospital Smallpox Vaccination-Monitoring System.
AB  - BACKGROUND: The Advisory Committee on Immunization Practices and the Healthcare
      Infection Control Practices Advisory Committee recommended that hospitals
      establish on-site, daily assessments of health care workers vaccinated with
      smallpox vaccine. The Hospital Smallpox Vaccination Monitoring System (HSVMS) was
      1 component of the smallpox vaccination plan to monitor adverse events on-site in
      hospitals. This report presents findings from February to August 2003. METHODS:
      All US institutions participating in the smallpox vaccination program were
      eligible to enroll in and use HSVMS through the Internet-based Centers for
      Disease Control Secure Data Network. RESULTS: Of the 730 enrolled vaccinees, 341
      (47%) were nurses; 122 (17%) physicians; 75 (10%) laboratory, patient care,
      radiology, or other technicians; 39 (5%) administrators; 22 (3%) housekeepers; 21
      (3%) physical or respiratory therapists; 20 (3%) infection control professionals;
      19 (3%) safety or security staff; and 17 (2%) epidemiologists; and 54 (7%) were
      workers in other job categories. Most (86%) vaccinees had been previously
      vaccinated. Postvaccination signs and symptoms were frequent: itching (75.2%),
      pain at the vaccination site (31.6%), swollen or tender lymph nodes (26.4%),
      fatigue (26.2%), and headache (20.8%). Symptoms were highest during the first
      week after vaccination; symptoms were more frequently reported among vaccinees
      without previous vaccination. Adherence to recommended vaccination site care was
      reported in 2732 of 3091 (88.4%) follow-up visits among workers with patient
      contact. Of the 4379 days workers planned to work, during 31 (0.7 per 100) days,
      workers performed restricted activities, and, in 60 (1.4 per 100) days, workers
      were absent. CONCLUSIONS: Findings from HSVMS indicate that adherence to post
      smallpox vaccination site care was high and that the number of days of work
      affected was low.

PMID- 16110600
TI  - Where sex and politics meet: sustaining behavior change.

PMID- 16110601
TI  - Principles involved in the treatment of acute and chronic empyema. 1924.

PMID- 16110602
TI  - Association of eye and neurological diseases.

PMID- 16110603
TI  - Occupational genotoxicity risk evaluation through the comet assay and the
      micronucleus test.

PMID- 16110604
TI  - The optimal discipline for assessing and managing pain during sex.

PMID- 16110605
TI  - Thymidylate synthase inhibitors.

PMID- 16110606
TI  - Anthracyclines.

PMID- 16110607
TI  - Tubulin-targeting agents.

PMID- 16110608
TI  - Recent developments in the clinical activity of topoisomerase-1 inhibitors.

PMID- 16110609
TI  - Topoisomerase II inhibitors.

PMID- 16110610
TI  - Farnesyltransferase inhibitors.

PMID- 16110611
TI  - Cyclin-dependent kinases as targets for cancer therapy.

PMID- 16110612
TI  - DNA-binding agents.

PMID- 16110613
TI  - Epidermal growth factor receptor pathway inhibitors.

PMID- 16110614
TI  - Angiogenesis pathway inhibitors.

PMID- 16110615
TI  - Prostate cancer antigens and vaccines, preclinical developments.

PMID- 16110616
TI  - Systemic therapy for renal cell carcinoma.

PMID- 16110617
TI  - Retargeting T cells and immune effector cells with bispecific antibodies.
AB  - The development of BiAbs for therapeutic applications in cancer shows promise. As
      our understanding of effector cell receptor biology for triggering of cytotoxic
      functions improves and the behavior of TAA and the targeting antibody engagement
      is elucidated, customized BiAb reagents can be engineered to optimize in vivo or
      ex vivo arming of T cells for targeting tumors. Additionally, other variables
      that require consideration in the equation for successful T cell immunotherapy
      include: the type of effector cells, their state of activation, the type of
      effector receptor being activated or tareeted. the presence of Tregs, the
      affinity of the anti-effector cell antibody and the anti-TAA antibody, the type
      of BiAb (mouse, humanized, or human), the number of binding sites for the T cells
      or TAA, the presence or absence of decoy antigen, whether the TAA modulates after
      being engaged by antibody, the type of tumor, the tumor burden, and last, but not
      least, the amount of 'immunologic' space available for the adoptively transferred
      cells to expand and function.

PMID- 16110618
TI  - T-cell genetic modification for re-directed tumor recognition.

PMID- 16110619
TI  - Cancer therapy-induced immune modulation.

PMID- 16110620
TI  - Plasma cell dyscrasias and leukemias.

PMID- 16110621
TI  - Lymphomas.

PMID- 16110622
TI  - Head and neck cancers.

PMID- 16110623
TI  - Lung cancer.

PMID- 16110624
TI  - Cancers of the large bowel and hepatobiliary tract.

PMID- 16110625
TI  - Neuroendocrine tumours.

PMID- 16110626
TI  - Genitourinary malignancies.

PMID- 16110627
TI  - Systemic therapy for gynecological neoplasms: ovary, cervix, and endometrium.

PMID- 16110628
TI  - Breast cancer.

PMID- 16110629
TI  - Melanoma.

PMID- 16110630
TI  - Soft-tissue and bone sarcomas.

PMID- 16110631
TI  - Central nervous system tumors.

PMID- 16110632
TI  - Biology and therapy of malignant solid tumors in childhood.

PMID- 16110633
TI  - Supportive care.

PMID- 16110634
TI  - AIDS-associated malignancies.

PMID- 16110635
TI  - Genetics, prevention and screening for melanoma.

PMID- 16110636
TI  - Current status of interferon-alpha in the treatment of melanoma.

PMID- 16110637
TI  - Chemotherapy, cytokines, and biochemotherapy for melanoma.

PMID- 16110638
TI  - Immunizing against partially defined antigen mixtures, gangliosides, or peptides
      to induce antibody, T cell, and clinical responses.

PMID- 16110639
TI  - DNA vaccines for melanoma.

PMID- 16110640
TI  - Human tumor associated antigen mimicry by xenoantigens, anti-idiotypic antibodies
      and peptide mimics: implications for immunotherapy of malignant diseases.

PMID- 16110641
TI  - Native and genetically engineered anti-disialoganglioside monoclonal antibody
      treatment of melanoma.

PMID- 16110642
TI  - A tragic error.

PMID- 16110643
TI  - Are we dying to be thin?

PMID- 16110644
TI  - [A conjecture on the fertilizer recovery measurement by field experiment].
AB  - The measurement of fertilizer recovery either by isotope tracer technique or by
      field experiment with plots fertilized and unfertilized, both were suspected
      unreliable and reasons were discussed. Based on some reasonable presumptions, an
      alternative way of estimating fertilizer recovery by field trials was proposed in
      this paper, but further examination on it's reliability is needed.

PMID- 16110645
TI  - [Litterfall in main forest ecosystems of Northeast China].
AB  - A three-year investigation on the litterfall of 15 forests in 4 different regions
      of Northeast China showed that the annual litterfall had a significant difference
      among forest types in the same region, but no significant difference was found
      between years. In the litterfall, leaf occupied 70% and more, while branch,
      flower and fruit were less than 20%. The branch production correlated positively
      with leaf production, and the correlation coefficient was 0. 82. According to the
      investigation of 5 forest types in Changbai Mountain, the litterfall was 2.62
      9.14 times higher in autumn and winter than in spring and summer. The peak of
      leaf-fall appeared in autumn, while that of branch and others withered evenly
      during a year. The litterfall of same forest type decreased with increasing
      latitude, and the relationships of the total and birch litterfall with latitude
      were established. Both the total and the birch litterfall were positively related
      to annual mean temperature, with the correlation coefficient 0.95 and 0.91,
      respectively.

PMID- 16110646
TI  - [Plantation stocks and their affecting factors in western Liaoning Province].
AB  - Employing real-site investigation and data analysis methods, this paper analyzed
      the distribution of plantation stocks and its affecting factors in western
      Liaoning Province. The results showed that the average plantation stock of
      western Liaoning was 49.08 m3.hm(-2), which has been improved obviously since
      1949. At the time of the third forest resource investigation, the plantation
      stock increased 20.19 m3.hm(-2), 5.16 times higher than that of the first forest
      resource investigation. But, the general plantation stock of western Liaoning was
      still at a rather lower level, with only a 63.5% increase of the whole province
      and 51.1% of the national average plantation stock at the same period. The
      difference of plantation stock among cities in western Liaoning was observable,
      that even reached 68.47 m3.hm(-2). In general, the proportion of young forest was
      too high, reached to 49 % of the total plantation, while the stock of mature
      forest was much lower, only 38% of the national average level. The plantation
      stock of national property was only 55.1% and 32.3% of the personal and
      collective property, respectively. Moreover, the plantation stock of timber
      forest was 36.4% lower than that of windbreak. Besides climatic factors, simple
      plantation structure, few forest tree species, and poor plantation management
      were the main causes of the low plantation stock.

PMID- 16110647
TI  - [Genetic diversity of Hepatacodium miconioides natural populations in Zhejiang
      Province].
AB  - Hepatacodium miconioides is the Class II protected plant species in China. This
      paper studied the genetic diversity and differentiation of its nine natural
      populations in Zhejiang Province by using random amplified polymorphic DNA (RAPD)
      technique. Twelve random primers were selected in the amplification, and 164
      repetitive loci were produced. The percentage of polymorphic loci in each H.
      miconioides population ranged from 14.60% to 27.44%, with an average of 20.73%.
      Among the test populations, Kuochangshan population had the highest percentage of
      polymorphic loci, Simingshan population took the second place, and Guanyinping
      population had the lowest one. As estimated by Shannon index, the genetic
      diversity within H. miconioides populations accounted for 27.28% of the total
      genetic diversity, while that among H. miconioides populations accounted for
      72.72%. The genetic differentiation among H. miconioides populations as estimated
      by Nei index was 0.7157. The genetic differentiation estimated by Nei index was
      generally consistent with that estimated by Shannon index, i.e., the genetic
      differentiation among populations was relatively high, but that within
      populations was relatively low. The gene flow among H. miconioides populations
      was relatively low (0.1987), and the genetic similarity ranged from 0.6557 to
      0.8119, with an average of 0.7306. The highest genetic distance among populations
      was 0.4229, while the lowest one was 0.2083. All the results showed that there
      was a distinct genetic differentiation among H. miconioides populations. The
      genetic distance matrix of nine test populations was calculated by using the
      method, and the clustering analysis was made by using the unweighted pair group
      method with arithmetic mean (UPGMA). The cluster analysis suggested that the nine
      populations of H. miconioides in Zhejiang Province could be divided into two
      groups, i.e., eastern Zhejiang group and western Zhejiang group.

PMID- 16110648
TI  - [Effects of polyethylene glycol (PEG)-simulated drought stress on Pinus
      sylvestris var. mongolica seed germination on sandy land].
AB  - With introduced sandy land Mongolian pine (Pinus sylvestris var. mongolica) seeds
      as test material, this paper studied the effects of polyethylene glycol (PEG)
      simulated drought stress on their germination. The results showed that PEG could
      retard the germination of stressed seeds, and the germination rate, germination
      index, and germination potential were all decreased with increasing PEG
      concentration. The seeds treated with 30% PEG (about -1.20 MPa water potential)
      could not germinate at all throughout the experiment period, suggesting that 30%
      PEG or -1.20 MPa water potential was the threshold for the germination of
      Mongolian pine seeds. Under 10% PEG stress (about -0.20 MPa water potential), the
      lengths of radicle and hypocotyl were shorter, illustrating their growth be more
      sensitive to PEG-simulated drought stress, while the radicle/hypocotyl ratio was
      increased with increasing PEG concentration, indicating that Mongolian pine seeds
      had a stronger resistance to drought stress after germination. Drought stress
      might be a possible cause that inhibited the natural regeneration of Mongolian
      pine on sandy land.

PMID- 16110649
TI  - [Effects of exogenous nitric oxide on drought-resistance of poplar].
AB  - This paper studied the effects of NO donor sodium nitroprusside (SNP) on the
      photosynthesis and active oxygen-scavenging enzyme activities of poplar leaves
      under drought stress. The results showed that SNP had a remarkable positive
      effect on leaf water content. When the SNP level was > 500 micromol.L(-1), no
      significant difference in leaf water content was found between SNP treatments.
      SNP could increase photosynthesis rate, photochemical efficiency of PSII
      (F(v)/F(m)), and ratios of F(m)/F(o) and F(v)/F(o), but the effects decreased
      with the prolongation of drought stress. The SOD and POD activities of poplar
      leaves were higher in short time (1 h) drought stress than in longer time (3 h)
      one. The activity of POD was increased by SNP, while that of SOD was changed
      little. With increasing SNP level, the POD and SOD activities first increased and
      then decreased. The NO donor could retard the accumulation of active oxygen
      through inducing POD and SOD activities, alleviate the effects of drought stress
      on photosynthesis, and increase the drought-resistance of poplar.

PMID- 16110650
TI  - [Dynamics of litterfall and its decomposition and nutrient return of shoot-used
      Dendrocalamus latiflorus in Mountainous areas of Fujian Province].
AB  - This paper studied the dynamics of nutrients in the litters of shoot-used
      Dendrocalamus latiflorus planted Nanjing State-owned Forest Farm of Fujian
      Province. The results showed that the litterfall as well as its nutrient
      concentration and return varied obviously with seasons, and had a double-peak
      curve change. The weight loss during litter decomposition was very fast at first,
      and then slowed down. There was a negative exponent correlation between remained
      weight and decomposition time. During decomposition, the concentrations of N and
      P in litter showed a trend of increase-decrease-increase, while the K loss was
      intensive at the early stage, gently at mid-stage, and slight at late stage.

PMID- 16110651
TI  - [Spatial and temporal pattern of Castanopsis fargesii seed rain in evergreen
      broad-leaved forest in Tiantong National Forest Park of Zhejiang, China].
AB  - Five mature plants of Castanopsis fargesii population were randomly chosen to
      study the spatial and temporal pattern of its seed rain in Tiantong National
      Forest Park, Zhejiang Province in 2003. The duration of seed rain observed from
      the five samples was about 45 days, from November 3rd to December 16th, with a
      distinguishable dropping peak between November 18th and 27th. The average seed
      rain density estimated from the traps deployed under the crown was 112.8 seeds.m(
      2), ranging from 70 to 239.5 seeds.m(-2). Of the total acorns collected by seed
      traps, the viable accounted for 27.3%, the immature 25.7%, the eaten by rodents
      5.0%, and the infected by larvae 42.0%. The acorns on the ground mainly
      distributed under the parent tree crown within 8 m from the trunk, and the
      spatial pattern of seed density on the ground fitted the quadratic distribution.

PMID- 16110652
TI  - [Dynamic characters of sulphur and heavy metals concentrations in Pinus
      taiwanensis growth rings].
AB  - Based on the concentration analyses of S, Mn, Fe, Zn, Cu and Pb in the growth
      ring set of Pinus taiwanensis at the summit (1,400-1,600 m alt.) of Huangshan
      Mountains during past 80 years, this paper studied the dynamic characters of
      element concentrations in the ring set, and their relationships with atmospheric
      environment. The results showed that there were three levels of S concentration
      in the growth ring set, i.e., low concentration (less than 2 mg.kg(-1)),
      accounted for 58.5% of the ring set; medium (3.65-6.0 mg.kg(-1)), accounted for
      24.4%; and high ( > 11.0 mg.kg(-1)), accounted for 17.1%. The dynamic change of S
      accumulation in the ring set displayed an obvious fluctuation, which could be
      divided into 3 major types, i.e., fluctuation during 1917-1960, relatively stable
      during 1961-1980, and gradual increase after 1981. In the growth ring set of 1935
      1938, 1959-1960, and recent 10 years, the S accumulation concentrations were all
      higher than 11 mg.kg(-1), suggesting the relatively high atmospheric S
      concentration in those periods. There was a significant correlation between the
      increase of tourist amount in Huangshan scenic spot and the S concentration in
      growth ring set. The fuel fume centralized in some places might result in the
      atmospheric pollution at local scale, which in turn, might influence the S
      accumulation in growth ring set. The Pb accumulation concentration in the ring
      set was less than the background value in soil. The accumulation concentrations
      of Mn, Fe, Zn and Cu showed fluctuation characteristics, with independence of
      each other. The accumulation of Zn and Cu in growth rings had no correlation with
      tree age, while that of Mn and Fe was in adverse. The Mn concentration in the
      growth ring set decreased with tree age but increased in recent growth rings,
      while the Fe concentration was on the contrary, which needed further study.

PMID- 16110653
TI  - [Landscape ecological evaluation of Fenglin Nature Reverse: quantification and
      interpretation].
AB  - Fenglin National Class Nature Reserve is the largest well-saved virginal Korean
      pine (Pinus koraiensis) forest area and a precious species gene bank in China. In
      this study, the indexes diversity, naturalness, representativity, rarity, area
      suitability, stability, and anthropogenic interference were selected to establish
      a ranking ecological evaluation system to estimate the ecological condition of
      the Reserve. The value of each index was determined by the evaluation system, and
      the weight percentage was decided by Analytical Hierarchy Process (AHP). In the
      Reserve, there were 568 higher plant species belonging to 113 families and 220
      higher animal species, with score 3 of species diversity. The zonal "climax"
      vegetation type broad-leaved Korean pine forest and the intrazonal community type
      spruce-fir forest constituted the principal part of the Reserve forest, which was
      the epitome of the virgin broad-leaved Korean pine forest in Lesser Xing'an
      Mountains, with representativity score 3. During the past 20-30 years, the
      natural habitat in the Reserve was quite good, and secondary succession was
      obtained effective control with few natural or anthropogenic disturbance, with
      score 4 of naturalness and anthropogenic interference. There were a lot of
      ancient species of the tertiary period, such as Pinus koraiensis, Fraxinus
      mandsurica, Juglans mandshurica, Pellodendron amurense, Tilia amurensis and Acer
      mono, and Pinus koraiensis was listed as one of severe danger species by the FAO
      of UN, with rarity score 4. The Reserve covered an area of 18165 hm2, with an
      enough size to maintain the structure and function of the ecosystem. Accordingly,
      its area suitability score was 4. Broad-leaved Korean pine forest was the most
      typical and stable vegetation type in the Reserve, and thus, its stability score
      was 4. Finally, the composite evaluation index (CEI) was figured out as 0.87,
      showing that the ecological quality of the Reserve was very good, and the
      protection value was quite high. In conclusion, the present area, structure, and
      management of the Reserve could satisfy the requirement of sustainable
      development.

PMID- 16110654
TI  - [GIS-based forest fire risk zone mapping in Daxing'an Mountains].
AB  - In this study, the Yuying and Fendou forest farms of Tuqiang Forest Bureau in
      Daxing'an Mountains were chosen as test areas, and their vegetation type,
      altitude, slop, aspect, and settlement buffer were selected as the main forest
      fire factors. The circumstances of forest fire risk were quantified by the factor
      weights union method with the support of GIS. Four classes of forest fire risk
      ranging from low to extreme were generated. The none-, low, moderate, high, and
      extremely high fire risk zones accounted for 0.37%, 0.63%, 38.67%, 58.63% and
      1.70%, respectively, which was in corresponding with normal distribution. About
      60.33% of the test areas were predicted to be upper moderate risk zones,
      indicating that the forest fire management task in these areas is super onerous.
      There was an obvious regional difference in the distribution of forest fire risk
      zones, being higher in the center and lower around the center, and the difference
      in fire factors was also obvious. The GIS-based forest fire risk model of test
      areas strongly cohered with the actual fire-affected sites in 1987, which
      suggested that the forest fire risk zone mapping had a higher reliability, and
      could be used as the reference and guidance of forest fire management.

PMID- 16110655
TI  - [Forest fire spread modeling and 3D visualization in virtual forest landscape].
AB  - The traditional method for simulating the behaviors of forest fire is to use a
      single ellipse to represent all of the fire points in fire scene, which has many
      disadvantages, e.g., the simulated result is quite different to the real
      situation, and it is mainly based on 2D. As a result, the represented information
      is limited. In this paper, the most widely used Rothermel fire spreading model
      and the principal of Huygen were adopted to simulate the behaviors of forest fire
      in different position and wind direction, and the results were shown by pseudo
      particle system in 3D, which could not only get the area of fire suffering, the
      direction of fire spreading and the size of fire, but also provide realistic
      simulation to observers. The method has been successfully applied to Zhangpu
      forest in Fujian Province.

PMID- 16110656
TI  - [Application of inverse Lagrangian dispersion analysis in simulating forest
      evapotranspiration].
AB  - Based on the localized near field (LNF) theory and coupled with the distribution
      of vertical velocity standard deviation (sigma(w)(z)) and Lagrangian integral
      time scales (T(L)(z)) within the canopy proposed by Raupach, the relationship
      between water vapor source/sink distribution and its mean concentration profile
      was constructed. The estimation of forest evapotranspiration was also conducted
      by the inverse Lagrangian dispersion analysis, which can calculate the water
      vapor source/sink distribution from its mean concentration profile. The
      calculated forest evapotranspiration was compared with the measured values. It
      was concluded that the simulated precision of the daily daytime
      evapotranspiration could reach 87.3%, the calculated results was 15 %-25% higher
      than the measured one, the nighttime evapotranspiration was about 70% of the
      daily value, and the total monthly evapotranspiration from June to August was
      higher than that in May and September.

PMID- 16110657
TI  - [Dynamic distribution characters of herbaceous vegetation root systems in
      abandoned grasslands of Loess Plateau].
AB  - The investigation on the vertical distribution characters of herbaceous
      vegetation root systems in abandoned and natural grasslands of Loess Plateau by
      the method of soil auger showed that there were no significant differences in
      root system distribution patterns between different sampling points, and the
      related root indexes could be used to indicate the vertical distribution
      characters of vegetation roots. The main root indexes including root biomass and
      root length were decreased with increasing soil depth, but increased with
      increasing abandoned years. After abandoned for more than 20 years, the root
      distribution characters of abandoned grassland were approached to that of natural
      grassland. The root extinction coefficient decreased with increasing abandoned
      years, indicating that more and more roots were concentrated in surface soil
      layer with the increase of abandoned time, which was helpful to the improvement
      of soil physical and chemical properties, and beneficial to the new species
      intrusion and vegetation succession.

PMID- 16110658
TI  - [Dynamics of bud flow and bud bank of Phragmites communis population in dry land
      habitat of alkalinized meadow in the Songnen Plains of China].
AB  - In the dry land habitat of alkalinized meadow in Songnen Plains, the rhizomes of
      Phragmites communis population are distributed in different depths of one meter
      soil layer, which usually live for 6 years and a few for 7-9 years or even
      longer. Based on the investigation of their buds, a "bud flow" model of the
      population was established, and the method for estimating the dynamics of its bud
      bank storage, i.e., adding the input rate of 1st year age-class rhizome buds to
      the storage rate of other age-classes dormant buds in the bank, was put forward.
      The results showed that the input rate of the bud bank increased with plant
      growth seasons while the burgeoned output rate exhibited a decreasing trend,
      whereas the output rate of the dead remained at a low level on the whole. By the
      end of September in the early dormant period, the input rate of the bud bank was
      as 2.04 times as its output rate, and the dormant buds of each age-class
      manifested a steady burgeoned output. Quantitative analysis indicated that the
      burgeoned output rate of dormant buds increased by 11% each year. In another
      word, 11% of different age-classes dormant buds would germinate and form one-year
      class new rhizomes. The top of one-year class new rhizomes would develop to
      ramets in the next year, which would transport nutrients to nearby old-age
      rhizomes, and thus, maintain the vitality of old-age class rhizomes.

PMID- 16110659
TI  - [Effects of environmental factors on AM fungi around steppe plant roots in Tibet
      Plateau].
AB  - The study on the representative steppe plant species in Tibet Plateau showed that
      the density of AM fungi spores in host plant rhizosphere did not correlate with
      the infection rate of AM fungi. The big changes in air temperature and rainfall
      at different altitudes played an important role in determining the growth and
      infection of AM fungi specific to steppe plants, and steppe type and soil texture
      also had obvious effects on AM fungi's growth and infection. Within a certain
      range, the spore density increased significantly with increasing soil pH (r =
      0.5319, n = 20), but showed a declining trend with the improvement of soil
      organic matter (r = - 0.1973, n = 20). In contrast, the infection rates of AM
      fungi to host plants were to some extent negatively and positively correlated
      with soil pH and soil organic matter, respectively. Phosphorus (P) enrichment in
      soil environment led to the inhibition of the reproduction and infection of AM
      fungi. The suitable soil pH, OM and Olsen P contents for the growth and
      reproduction of AM fungi ranged from 8.0-8.7, 3.8-4.8 g.kg(-l) and 7.8-10.1
      mg.kg(-1), respectively. Moderate and serious degradation of steppe (especially
      the serious degradation) had negative or detrimental impacts on the reproduction
      and infection of AM fungi. Reasonable grazing was helpful to the conservation of
      critical species of AM fungi. AM fungi also showed a relatively high infection
      rate on the roots of sedge species such as Carex praecpara, Kobresia humilis and
      Cyperus compressus.

PMID- 16110660
TI  - [Effects of AM fungi on drought tolerance of citrus grafting seedling trifoliate
      orange/cara cara].
AB  - With pot experiment in a greenhouse, this paper studied the effects of arbuscular
      mycorrhizal (AM) fungi Glomus mosseae on the drought tolerance of citrus grafting
      seedling trifoliate orange/cara cara under natural water stress and rewatering.
      The results showed that inoculation with AM fungi significantly increased the
      plant height, stem diameter, leaf area, and shoot length of test seedling. At the
      4th day of rewatering, mycorrhizal plant had significantly higher root soluble
      protein content and superoxide dismutase (SOD) and catalase (CAT) activities than
      non-mycorrhizal plant. An interaction between water and AM fungi could
      significantly promote leaf SOD activity. During natural water stress and
      rewatering, AM fungi inoculation could decrease the leaf content of
      malondialdehyde (MDA), increase those of soluble sugar and soluble protein, and
      enhance the activities of SOD, peroxidase (POD) and CAT. As a result, the
      capability of osmotic adjustment and protective recovery, and thus, the drought
      tolerance of mycorrhizal citrus grafting seedling were improved. The mechanism
      that AM fungi could enhance the drought tolerance of host plant might be related
      to the protective system of host plant.

PMID- 16110661
TI  - [Dendrolimus spp. damage monitoring by using NOAA/AVHRR data].
AB  - This paper approached the feasibility of quantitatively monitoring Dendrolimus
      spp. damage by using NOAA/ AVHRR data. The damaged rate of needle leaf was used
      to represent Dendrolimus spp. harming degree, and < 30%, 30%-60% and > 60% of
      damaged rate was defined as low, medium and severe harming degree, respectively.
      The correlation equation of damaged rate and normalized vegetation index (NDVI)
      was established, based on the ground spectrum observation. The NDVI was 0.8823
      when no damage occurred. A relative NDVI value of damaged to undamaged area was
      used to express the remote sensing index of low, medium and severe harming
      degree. The index was 1 for undamaged forest, and 0.78-1, 0.57-0.78 and < 0.57
      for low, medium and severe harming degrees, respectively. The mixed pixels were
      separated by linear addable vertical vegetation index in the monitoring, and the
      quantitative monitoring and analysis was accomplished for years when the three
      damage degrees happened. It was shown that AVHRR data could be more available in
      quantitatively monitoring and analyzing serious damage, while low degree damage
      was difficult to distinguish by AVHRR data, due to the differences of surface
      properties and atmospheric influences, as well as the lower space resolution of
      NOAA/AVHRR. The damaged area estimated by AVHRR was 12.1%-14.3% lower than that
      by TM.

PMID- 16110662
TI  - [Dynamics of fluvo-aquic soil organic matter fractions under long-term
      fertilization].
AB  - By the method of relative density fractionation, this paper studied the dynamics
      of organic matter and its light and heavy fractions in a fluvo-aquic soil under
      long-term fertilization. The results indicated under current fertilization
      system, the contents of soil organic matter and its light and heavy fractions
      were basically unchanged within 13 successive years of no fertilization, but had
      an increasing trend with the duration of chemical fertilizer NPK and organic
      manure applications, with a larger fluctuation among years and a less increment
      in treatment NPK. Regression analysis showed that soil organic matter and its
      light and heavy fractions had a linear correlation with the duration of
      fertilization in treatment NPK, and had a logarithm correlation in treatment
      organic manure.

PMID- 16110663
TI  - [Individual grain yield potential and nitrogen utilization efficiency of Zea mays
      cultivars widely planted in North China].
AB  - With field experiment and under low-density condition, this paper studied the
      individual grain yield (GY) and nitrogen utilization efficiency (NUE) of fifty
      Zea mays cultivars widely planted in North China since 1990s. Exploring analyses
      and normality tests showed that the 1000-kernal weight (KW), above-ground biomass
      per plant (AB), grain harvest index (HI(G)), NUE, and nitrogen harvest index
      (HI(N)) were all conformed to normal distribution, with N (265.1, 44.50(2)), N
      (322.3, 36.91(2)), N (515.8, 64.73(2)), N (0.514, 0.06(2)), N (43.0, 5.37(2)),
      and N (0.643, 0.06(2)), respectively. The GY ranged from 198.35 to 345.22
      g.plant(-1), KW from 241.50 to 391.82 g.1000 kernal(-1), AB from 402.34 to 712.84
      g.plant(-1), HI(G) from 0.39 to 0.63, NUE from 31.18 to 57.35 g grain.g N(-1),
      and HI(N) from 0.47 to 0.74. Correlation analyses indicated that GY positively
      and significantly correlated with NUE (partial correlation coefficient was 0.471,
      P = 0.001), while KW negatively and significantly correlated with NUE (Pearson
      correlation coefficient was -0.427, P = 0.002). Through hierarchical cluster
      analyses for GY and NUE, the test Zea mays varieties could be sorted into 3
      types, i.e., high-GY with high-NEU, low-GY with low-NEU, and mediate type.
      Currently, only 24 percent of Zea mays cultivars in North China were of high-GY
      with high-NEU type, and thus, its breeding should be strengthened in the future.

PMID- 16110664
TI  - [Allelopathy and resources competition of rice under different nitrogen
      supplies].
AB  - In order to explore the bio-interference of allelopathic rice with barnyardgrass
      under different nitrogen supplies, a new bioassay method, i.e., allelopathy
      competition separation based (ACS) approach was recommended in this study. The
      results indicated that ACS could be successfully used to distinguish the rice
      allelopathy from its resources competition in rice-weed co-culture system, and to
      evaluate its response characteristics under different N supplies. The test rice
      accession PI312777 had a higher ability in interfering target weed barnyardgrass
      (BYD), represented by its stable and higher ability in resources competition, as
      well as its increasing allelopathic potential in suppressing companion weed BYD
      when the N supply decreased in the co-cultured system. The reverse was true in
      the case of rice accession Lemont, which had a lower allelopathic potential under
      all N supply levels, and a lower ability in resources competition under normal or
      rich N supply. But, Lemont had an obviously increased ability in resources
      competition under lower N supply, which was considered as the result of econiche
      competition in rice-weed system.

PMID- 16110665
TI  - [Interactive effects between allelochemical substitutes].
AB  - In order to understand the allelopathic mechanisms of rice on weed, the
      allelochemical substitutes salicylic acid, p-hydroxybenzonic acid, cinnamic acid,
      vanillic acid and ferulic acid were used in an orthogonally gyrating regression
      experiment to study their interactive effects on the growth of barnyardgrass. The
      results indicated that whether the interactive effects between two substitutes,
      e.g., between salicylic and cinnamic acid or between salicylic and p
      hydrobanzonic acid, were synergistic or antagonistic depended on the
      concentrations of each substitutes in the mixture. In the mixture of salicylic
      acid and p-hydrobanzonic acid, the effect of salicylic acid was synergistic at <
      0.14 mmol.L(-1) but antagonistic at > 0.14 mmol.L(-1), while p-hydrobanzonic acid
      showed an antagonistic effect at > 0.425 mmol.L(-1). Salicylic acid at all test
      concentrations exhibited antagonism to cinnamic acid, while cinnamic acid had a
      synergistic at < 0.14 mmol.L(-1), but an antagonistic effect at >0.14 mmol.L(-1)
      on alicylic acid. The interactive effects between cinnamic and ferulic acid were
      all synergistic at test concentrations.

PMID- 16110666
TI  - [Effects of pesticides metolachlor and S-metolachlor on soil microorganisms in
      aquisols of Southern China. I. Catalase activity].
AB  - This paper studied the effects of different concentrations (0, 5, 20, and 100
      mg.kg(-1)) metolachlor and its enantiomer S-metolachlor (Dual Gold) on soil
      catalase activity. The results showed that 20 mg.kg(-1) metolachlor had the most
      successive stimulating effect, 5 mg.kg(-1) metolachlor had an inhibitory effect
      in the early period, while 100 mg.kg(-1) metolachlor had a stimulating effect in
      the late period. Different concentrations Dual Gold displayed a tendency
      stimulation-inhibition-stimulation. 5 and 100 mg.kg(-1) metolachlor might have
      more damage on soil ecosystem than different concentrations Dual Gold.

PMID- 16110667
TI  - [Forms and bio-availabilities of exogenous arsenic in purple soils].
AB  - This study showed that after As was added into purple soils for 10 days, 50.2%
      61.1% of it transformed into residual As, occupying 68%-86% in original soils.
      For acid purple soil, the As forms were Al-As > Fe-As> Ca-As; for neutral purple
      soil, they were Ca-As > Al-As > Ca-As > Fe-As > A-As, and for calcic purple soil,
      they were Ca-As > Al-As > Fe-As >A-As. It is suggested that NH4Cl could be used
      as common extractant for different soils, because it slightly affected original
      As forms in soils, and showed a highly significant correlation (P = 0.01) to
      plant absorption. From pluralistic regressive analysis of plant As content and
      each As form, Al-As and Fe-As were the main available forms in acid purple soil,
      but A-As and Ca-As were the most important fractions in neutral and calcic purple
      soils. The study also showed that H3BO3 could restrain the F interference in the
      operation of As speciation separations.

PMID- 16110668
TI  - [Maize growth and phosphorous- and zinc uptake under different phosphorous supply
      levels].
AB  - By the method of solution culture, this paper studied the P and Zn uptake of
      maize at its growth stages under different P supply levels. The results showed
      that maize growth reached its maximum at the supply level of 100 micromol P.L(
      1), while the root/shoot ratio was the highest at 0.1 micromol.L(-1) P supply.
      Increase of P concentration in culture solution promoted the uptake of P, but
      decreased its utilization rate. The Zn content in root increased with increasing
      P supply, while that in shoot varied little, which meant that the Zn
      transportation rate from root to shoot had little change with increasing P
      concentration. There was a positive correlation between the concentrations of Zn
      and P in maize seedling roots.

PMID- 16110669
TI  - [Analysis and identification of Liriomyza sativae-attractants from cowpea and
      kidney bean volatiles].
AB  - In this paper, the volatiles from cowpea and kidney bean, the main host plants of
      American leafminer Liriomyza sativae, were collected and extracted by a self
      designed device and solid phase microextraction (SPME) technique, and analyzed by
      GC-MS. The results showed that the volatiles from the two beans had the same
      components mainly consisted of 2-hexenal, 3-Hexen-1-ol, 2-Hexen-1-ol, 1-Octen-3
      ol, 3-Hexenol acetate, alpha-Ionone and beta-Ionone. The lure made of the seven
      components was attractive to L. sativae in field trapping trials. Detailed
      analyses indicated that alpha-Ionone and beta-Ionone might play important roles
      in the searching behavior of L. sativae for host plants.

PMID- 16110670
TI  - [Population fluctuation of main pathogens and their antagonistic bacteria in
      cucumber rhizosphere].
AB  - The investigation on the population fluctuation of main pathogens Pythium spp.
      and Fusarium oxysporum f. cucumerinum in the rhizosphere of four cucumber
      varieties showed that there was a significant difference in population number of
      pathogens for different cucumber varieties and for different growth stages of the
      same variety, which was in accordance with the regular disease incidence pattern.
      The population number of Pythium spp. was significantly higher at cucumber
      creeping stage than at its other growth stages, while that of Fusarium oxysporum
      f. sp. cucumerinum was the highest at cucumber principal-fruiting stage. There
      was a closer positive relationship between two test pathogens and their
      antagonistic bacteria, with the correlation coefficient being 0.95 and 0.81,
      respectively.

PMID- 16110671
TI  - [Effects of cinnamic acid on physiological characteristics of Cucumis sativus
      seedling].
AB  - With substrate culture, this paper studied the effects of different
      concentrations of cinnamic acid on the physiological characteristics of Cucumis
      sativus seedling. The results showed that 25 micromol.L(-1) of cinnamic acid had
      an inhibition effect on carotenoids, but a promotion effect on chlorophyll a and
      b. 50 micromol.L(-1) of this compound could significantly inhibit the
      photosynthetic rate, transpiration rate and root activity (P < 0.05), and this
      effect was getting stronger when the concentration was higher. 150 micromol
      cinnamic acid.L(-1) had a significant inhibition effect on chlorophyll a and b (P
      < 0.05). Cinnamic acid had a weak inhibition effect on root activity when its
      concentration was low (25-50 micromol.L(-1)), but the effect was significant when
      the concentration was high (100-150 micromol.L(-1)), which became stronger with
      the longer handling time (P < 0.05).

PMID- 16110672
TI  - [Effects of Colletotrichum higginsianum infection on endogenous hormones in
      Brassica parachinensis leaves under different nitrogen nutrition].
AB  - This paper studied the effects of Colletotrichum higginsianum infection on the
      ethylene production and the contents of abscisic acid (ABA) and indole-3-acetic
      acid (IAA) in leaves of flowering Chinese cabbage (Brassica parachinensis) under
      six levels of nitrogen (N) nutrition, and their relations to disease-resistance.
      The results showed that the ethylene production in all N treatments had a mono
      peak curve change, and reached the maximum 4-6 days after inoculation. In
      comparing with high N or non-N treatment, medium or low N treatment could inhibit
      ethylene production and ABA synthesis, and keep ethylene and ABA stable in
      Colletotrichum higginsianum-inoculated plants. The IAA content in medium or low N
      treatment increased gradually, while that in high N or non-N treatment had a mono
      peak curve change, and reached the maximum 4-6 days after inoculation. The IAA
      content in medium or low N treatment increased more with inoculation time,
      indicating that there was a close relationship among N nutrition, endogenous
      hormones and anthracnose. It is important for plants' disease-resistance to keep
      the balance of endogenous hormones.

PMID- 16110673
TI  - [Effects of free-air CO2 enrichment (FACE) on phosphorus nutrition of Oryza
      sativa at its different growth stages].
AB  - Using free-air CO2 enrichment (FACE) platform and under different nitrogen supply
      level, this paper studied the phosphorus nutrition of Oryza sativa at its
      different growth stages. The CO2 concentration of FACE platform was 200
      micromol.mol(-1) more than that in ambient air, and the nitrogen supply levels
      were 150 kg.hm(-2), 250 kg.hm(-2) and 280 kg.hm(-2). The results showed that
      during rice growth period, FACE significantly increased the phosphorus content of
      rice plant and its phosphorus uptake by 3.9%-20.6% and 28.9%-71.4%, respectively.
      Before heading, FACE had little effect on the phosphorous accumulation in leaf or
      stake, but after heading, made the proportion of phosphorus accumulation in
      reproductive organ decreased by 9.8%-26.3% and that in vegetative organ increased
      by 2.2%-23.9% at 0.01 or 0.05 significant level. Under FACE treatment, the
      phosphorus use efficiency for biomass production (PUEp) at different growth
      stages, the phosphorus use efficiency for grain output (PUEg), and the phosphorus
      harvest index (PHI) were decreased by 3.7%-16.6%, 6.5% -15.5%, 5.4%-9.0%,
      respectively. Nitrogen supply level and its interaction with FACE had less effect
      on the phosphorus-nutrition of rice at its different growth stages.

PMID- 16110674
TI  - [Concentrations of metallic elements, N and S in Sabina chinensis cv. pyramidalis
      leaves along urban-rural roadways of Nanjing city].
AB  - This paper measured the concentrations of metallic elements, N and S in soils and
      Sabina chinensis cv. pyramidalis leaves along the urban-rural roadways (urban
      trunk roads, belt highway, and suburban roads) of Nanjing city, with botanical
      garden as un-traffic impacted reference site, and discussed the transfer of test
      elements among atmosphere, plant and soil, as well as the impact of traffic
      related pollution. The results showed that the concentrations of Al, Fe, Mo, Zn,
      Cd, Pb, As and Cr in Sabina chinensis leaves were significantly higher along
      urban-rural roadways than at reference site, being most remarkable for Al, Fe, Mo
      and Zn. The positive correlations between soil and Sabina chinensis leaf Fe, Zn
      and As concentrations in road environment indicated that Sabina chinensis might
      be a good indicator plant of soil Fe, Zn and As. The correlations between soil
      and plant leaf Al, Mo, Cu, Pb, Cd and Cr concentrations were not remarkable, and
      thus, their high concentrations in Sabina chinensis leaf in road environment
      might be caused by air pollution. The concentrations of N and S in Sabina
      chinensis leaf were higher along urban trunk roads and belt highway than at
      reference site, while those along suburban roads were similar to the reference.
      There was a negative correlation between soil and plant leaf N, and a positive
      correlation between soil and plant leaf S. The N content in roadside soil was
      lower, while the S content was higher than the reference, indicating that the
      higher Sabina chinensis leaf N content in road environment might be caused by the
      NO(x) from exhaust gas emission, and the higher leaf S content should be come
      from soil.

PMID- 16110675
TI  - [Responses of antioxidation system of Cynodon dactylon to recirculated landfill
      leachate irrigation].
AB  - With pot experiment, this paper studied the membrane lipid peroxidation and the
      variations of antioxidation system in Cynodon dactylon under recirculated
      landfill leachate irrigation. The results showed that when irrigated with low
      dilution ratio (< 25%) leachate, the chlorophyll a/b ratio increased with
      increasing dilution ratio, membrane permeability and MDA and H2O2 contents were
      in adverse, and membrane lipid peroxidation was relatively weak. However, with
      the increasing leachate dilution ratio (> 25%), there existed an obvious negative
      fect on Cynodon dactylon, i.e., the chlorophyll a/b ratio decreased, while cell
      membrane permeability and MDA and H2O2 contents increased, which meant that the
      membrane lipid peroxidation was accelerated. The contents antioxidants AsA, GSH
      and Car also showed the similar trend, i.e., they increased with increasing
      leachate dilution ratio when irrigated with low dilution ratio leachate, but
      decreased under medium or high dilution ratio leachate irrigation. Among three
      test anti-oxidative enzymes, SOD and POD activities showed a similar change test
      antioxidants, and POD activity was more sensitive, while CAT activity was on the
      contrary. The contents test antioxidants and the activities of SOD and POD were
      negatively and significantly correlated to MDA content, indicating that they
      might play an important role in preventing Cynodon dactylon from cell membrane
      lipid peroxdation.

PMID- 16110676
TI  - [Spatial variation of microbial properties in a creosote-contaminated soil].
AB  - By the methods of geostatistics, this paper studied the spatial variation of
      microbial biomass, microbial community structure and microbial activity in a
      creosote-contaminated soil. The microbial biomass was indicated by the total
      amount of 26 examined phospholipid fatty acids (totPLFA), the microbial community
      structure was characterized by the first two principal components (PC1 and PC2)
      of the PLFA patterns through subjecting the PLFAs to principal component
      analysis, and the total amount of CO2-C respired (C(re)) during incubation was
      used to describe the soil microbial activity. The results showed that most of the
      variables exhibited various degrees of spatial autocorrelation, and spherical
      models with nugget could fit their semivariograms. The estimated spatial
      dependence distances of the variables varied from 2.50 to 16.60 m. The PLFA PC1,
      totPLFA and C(re) displayed relatively high spatial dependences, their relative
      structural variance, i.e., the proportion of total variance that can be
      attributed to the spatial autocorrelation, being 82.3%, 79.6% and 64.7%,
      respectively, while PLFA PC2 was not spatially autocorrelated. The kriged maps
      showed that there were several hot spots with relatively high microbial biomass
      and high microbial activity located in the study site. Gram- negative bacteria
      characterized by PLFAs 16:1omega7t, cyl7:0, 18:1omega7 and cyl9:0 were the
      dominant community in these hot spots. The concentration and spatial distribution
      of polycyclic aromatic hydrocarbons as the main contaminants in the soil could be
      one of the important factors affecting the spatial variation of soil microbial
      properties.

PMID- 16110677
TI  - [Phytoremediation of mercury and cadmium polluted wetland by Arundo donax].
AB  - With a pot culture of simulated mercury (Hg) and cadmium (Cd)-polluted wetland,
      this paper studied the capability of Arundo donax in accumulating these heavy
      metals, and their distribution in the plant. The results showed that after grown
      in a 101 mg.kg(-1) Hg-polluted wetland for 8 months, the Hg-concentrating
      capability of Arundo donax was in order of root > stem > leaf, and the Hg
      concentration in its aboveground parts was 200 +/- 20 mg.kg(-1) (DW); while in
      the case of 115 mg.kg(-1) Cd-pollution, the Cd-concentrating capability was in
      order of leaf > root > stem, and the Cd concentration in leaf was 160 +/- 26
      mg.kg(-1) (DW). The heavy metals concentration in Arundo donax organs increased
      with its growth time, being 30%-50% higher for 8 months than for 4 months. The
      BCF (Bio-concentration factor) decreased with increasing heavy metals
      concentration. In polluted wetland, the BCFs of Hg by the leaf and stem were 1.9
      and 2.1, and those of Cd were 1.5 and 0.3, respectively; while in unpolluted
      wetland, the concentration of Hg and Cd was 6.8 and 8.5 mg.kg(-1), the BCFs of Hg
      by the leaf and stem were 6.8 and 12.2, and those of Cd were 7.0 and 2.7,
      respectively. It was indicated that Arundo donax not only had the characters of
      large biomass, exuberant root, and good adaptability, but also exhibited high
      tolerance and concentrating capability to Cd and Hg.

PMID- 16110678
TI  - [Effects of simulated nitrogen deposition on weeds growth and nitrogen uptake].
AB  - In this paper, a greenhouse experiment was conducted to study the responses of
      different functional groups weeds to simulated nitrogen deposition (4.0 g N.m(
      2).yr(-1)). Native weed species Poa annua, Lolium perenne, Avena fatua, Medicago
      lupulina, Trifolium repens, Plantago virginica, Veronica didyma, Echinochloa
      crusgalli var. mitis, Eleusine indica and Amaranthus spinosus in orchard
      ecosystem were used test materials, and their above-and underground biomass and
      nitrogen uptake were measured. The results showed that under simulated N
      deposition, the total biomass, shoot biomass and root biomass of all weed species
      tended increase, while the total biomass was differed for different functional
      groups of weeds. The biomass of C4 grass, legumes and C3 grass was significantly
      increased under N deposition, while that of C3 and C4 forbs was not significantly
      impacted. The root/shoot biomass ratio of Avena fatua and Plantago virginica was
      enhanced by N deposition, but that of Poa annu, Lolium perenne, Medicago
      lupulina, Trifolium repens and Amarathus spinosus was not impacted significantly.
      N deposition had no significant effect on plant N concentration, but
      significantly enhanced the N uptake of all test weed species except Amarathus
      spinosus, Poa annua and Veronica didyma. was suggested that the further increase
      of N deposition might speed up the changes of the community structure weed
      species due to their different responses to N deposition.

PMID- 16110679
TI  - [Extraction method of soil microbial DNA for molecular ecology study].
AB  - In environmental microbiology, molecular ecology study has been widely concerned
      in the world, while high quality DNA is the basis of the study. In our study,
      soil microbial DNA was extracted by the methods of SDS lysis denaturant plus SDS
      lysis, and purified with gel electrophoresis plus minicolumn and double
      minicolumn methods. The results showed that denaturant plus SDS lysis could
      extract DNA more efficiently, and gel electrophoresis plus minicolumn could help
      to obtain purer DNA that was available in amplifying its 16S rDNA and functional
      genes by PCR. Therefore, denaturant plus SDS lysis could be an efficient and
      reliable method to extract DNA molecular ecology studies.

PMID- 16110680
TI  - [Carrying capacity of shellfish culture in Dadeng Island sea area of Xiamen].
AB  - To fully and rationally exploit local living marine resources while have a
      sustainable, efficient and healthy development of shellfish culture in the Dadeng
      Island sea area of Xiamen, this paper determined and analyzed the related model
      parameters of this area, including chlorophyll a, primary productivity,
      phytoplankton organic carbon tent, wild filter feeder yields in subtidal and
      intertidal zones and suspension culture area, cultured shellfish filtration rate
      and organic carbon content, shellfish's total weight to fresh meat ratio, and
      adopted the Nutrient namic Model and Coastal Waters' Energy Flow Analysis Model
      to estimate the ecological capacity of shellfish this area, from which, the wild
      filter feeder yields were deducted for estimating shellfish carrying capacity.
      model established by Fang Jianguang was also used to estimate the shellfish
      carrying capacity. Statistics analysis was used to estimate the suitable culture
      area of shellfish and other species, aiming at limiting local shellfish ture and
      optimizing the culture of various species mollusks. According to the estimation
      of the three models, shellfish carrying capacity in this area should be 35,248
      39,990 tons, with an average of 37,488 tons, 140,008 x 10(4) - 158,850 x 10(4)
      individuals, averaging 148,903 x 10(4). The theoretically suitable culture area 2
      145 hm2, 1,900 hm2 for Ostreidae, 81 hm2 for razor clam (Sinonovacula
      constricta), 20 hm2 for blood (Tegillarca granosa), and 144 hm2 for musculus
      (Musculus senhousei). In 2000, the actual culture area of shellfish and other
      species in the waters around Dadeng surpassed the estimated suitable culture
      area. It is proposed that some measures should be taken to reduce the
      overexploited area.

PMID- 16110681
TI  - [Effects of culture condition on fatty acids in Pseudcarbomonas sp].
AB  - The investigation on the growth of Pseudomonas sp. and the dynamics of its fatty
      acids under various culture conditions indicated that the optimum temperature for
      its growth was 30 degrees C, and the best carbon source was starch. 13 kinds of
      fatty acids were detected, among which, c16:1(n-7), c15:0, c16:0, c17:0, c18:1(n
      6), c18:1 (n-9), 9, 10-cp-c17:0 and iso9, 10-cp-c17:0 were the major ones. When
      cultured at 30 degrees C, the relative content of unsaturated fatty acids
      decreased significantly. Carbon source in the media was the crucial factor
      affecting the contents of odd- and cyclopropane fatty acids. Cluster analysis
      revealed that temperature had a more obvious effect than carbon source.

PMID- 16110682
TI  - [Roles of calcium in stress-tolerance of plants and its ecological significance].
AB  - Calcium loss from soil has dramatically increased for decades due to the increase
      of nitrogen input and/or the extension of acid rain, while calcium input into
      soil has declined substantially for the replacement of superphosphate by ammonium
      phosphate in fertilization, which intensified the imbalance of calcium input and
      output in agro-ecosystems, and needed to be solved in the near future for the
      sustainability of agriculture in such a country like China where the arable land
      resource is very limited. In recent years, the intensified soil acidification is
      mainly attributed to the root proton secretion stimulated by fertilization, and
      the nitrogen input from precipitation near industrialized regions promotes plant
      growth but results in other nutrients deficiency, which in turn acidifies soil
      and causes tree death. One of the most important mechanisms of saline soil
      bioremediation by sesbania is the activation of soil calcium by sesbania's proton
      secretion and the increase of soil calcium supply for subsequent crops. The
      present paper summarized the roles of calcium in plant tolerance to the stresses
      like acidosis, toxic metals, osmosis, ammonium toxicity, drought, extreme
      temperature (cold or heat shock), anoxia and pathogen infection, and the measures
      for maintaining soil calcium fertility. It was suggested that the production of
      ammonium phosphate should not be a pursued target for China's phosphorus
      fertilizer industry, and the roles of calcium in plant growth should be taken
      into account in fertilization experimental designs to make the experiments more
      accurate.

PMID- 16110683
TI  - [A landscape ecological approach for urban non-point source pollution control].
AB  - Urban non-point source pollution is a new problem appeared with the speeding
      development of urbanization. The particularity of urban land use and the increase
      of impervious surface area make urban non-point source pollution differ from
      agricultural non-point source pollution, and more difficult to control. Best
      Management Practices (BMPs) are the effective practices commonly applied in
      controlling urban non-point source pollution, mainly adopting local repairing
      practices to control the pollutants in surface runoff. Because of the close
      relationship between urban land use patterns and non-point source pollution, it
      would be rational to combine the landscape ecological planning with local BMPs to
      control the urban non-point source pollution, which needs, firstly, analyzing and
      evaluating the influence of landscape structure on water-bodies, pollution
      sources and pollutant removal processes to define the relationships between
      landscape spatial pattern and non-point source pollution and to decide the key
      polluted fields, and secondly, adjusting inherent landscape structures or/and
      joining new landscape factors to form new landscape pattern, and combining
      landscape planning and management through applying BMPs into planning to improve
      urban landscape heterogeneity and to control urban non-point source pollution.

PMID- 16110684
TI  - [Effects of Pb2+ and Cd2+ pollution on physiological characteristics of Thuidium
      cymbifolium].
AB  - This paper dealt with the effects of Pb2+, Cd2+ and their combined pollution on
      the contents of chlorophyll, potassium and calcium in Thuidium cymbifolium. The
      results showed that except at 0.1 mg Cd2+.L(-1), the chlorophyll content
      decreased with increasing Pb2+ and Cd2+ concentrations, which was 18% of the
      control at 100 mg Cd2+.L(-1), and decreased by 48.6% at 200 mg Pb2+.L(-1). The
      potassium and calcium contents also decreased with increasing pollutants
      concentrations, being decreased by 61.1% at 100 mg Cd2+.L(-1). Cd2+ had a
      stronger toxicity than Pb2+, and the toxicity of their combined pollution was
      stronger than that of each pollutant. Pb2+ could increase the toxicity of Cd2+.

PMID- 16110685
TI  - Suicide by aircraft: a comparative analysis.
AB  - INTRODUCTION: Suicide is the 11 th leading cause of death in the United States.
      The objective of this study is to document the characteristics of aviation
      related suicides and suicide attempts. METHODS: Aviation accidents reported by
      the National Transportation Safety Board between 1983 and 2003 were screened for
      cases in which suicide was listed as a probable cause. For each suicide case, two
      accidents were randomly selected as controls, matched on sex of pilot, type of
      flight, state, and year of occurrence. Mantel-Haenszel summary Chi-square tests
      were used to compare cases to controls. Conditional logistic regression modeling
      was performed to assess the association of pilot and flight characteristics with
      suicide-related crashes. RESULTS: During the 21-yr study period, 37 pilots
      committed or attempted suicide by aircraft, with 36 resulting in at least one
      fatality. All the cases were men and involved general aviation flights.
      Toxicological test results revealed that 24% of the cases had used alcohol and
      14% had used other illicit drugs. Underlying factors included domestic and social
      problems (46%), legal trouble (40%), and pre-existing psychiatric conditions
      (38%). Compared with controls, suicide cases involved younger pilots (p < 0.05),
      were less likely to have another occupant (p < 0.0001), were more destructive to
      the aircraft (p < 0.0001), and were more likely to have occurred away from the
      airport (p < 0.0001). CONCLUSION: Aviation crashes caused by suicide differ from
      unintentional aviation accidents in pilot characteristics, crash circumstances,
      and outcomes.

PMID- 16110686
TI  - Monocyte adhesion to endothelial cells increases with hind-limb unloading in
      rats.
AB  - INTRODUCTION: [corrected] Hind-limb unloading (HU) in rodents has been used as a
      model to simulate some effects of spaceflight on the musculoskeletal,
      cardiovascular, and immune systems in humans. HU leads to redistribution of
      extracellular fluid to the upper half of the body. We hypothesized that altered
      blood flow might induce intercellular adhesion molecule-1 (ICAM-1) expression of
      arterial endothelial cells and increase monocyte-endothelial adhesion. METHODS:
      Male Sprague-Dawley rats were randomly assigned to either a control, 7-d HU, or
      28-d HU group. The expression of ICAM-1 and monocyte adhesion was determined by
      immunohistochemistry. RESULTS: In control rats, ICAM-1 was not expressed in all
      vessels studied. HU induced the ICAM-1 expression in the carotid artery and
      thoracic aorta, but did not in the femoral artery. Staining density of ICAM-1
      expression was stronger in the 28-d HU group than in the 7-d HU group.
      Endothelial-monocyte adhesion was significantly increased in the carotid artery
      and thoracic aorta from the HU groups compared with the control group, but
      completely absent in the femoral arteries of both the HU and control groups. In
      the thoracic aorta, but not in the carotid artery, endothelial-monocyte adhesion
      was more increased after 28-d HU than after 7-d HU. CONCLUSION: These data
      indicate that an increase in shear stress induced by HU stimulates ICAM-1
      expression on arteries, which contributes to adhesion of monocytes on their
      endothelium. Reduced shear stress has no effects on monocyte adhesion.

PMID- 16110687
TI  - Leukocyte subset responses during exercise under heat stress with carbohydrate or
      water intake.
AB  - PURPOSE: This study investigated leukocyte subset responses to moderate-intensity
      exercise under heat stress, with water (W) or carbohydrate (CHO) drink ingestion.
      METHODS: In repeated trials, 13 soldiers consumed either a W or CHO drink during
      3 h of walking at 4.4 km x h(-1) with a 5% gradient (15 min rest per hour) under
      heat stress (35 degrees C and 55% relative humidity). The soldiers wore combat
      uniforms and carried water bottles and dummy rifles and ammunition, altogether
      weighing about 11.5 +/- 1.0 kg. RESULTS: Plasma glucose concentration was
      significantly higher with CHO than W ingestion during exercise (p < 0.01). There
      were no significant differences between W and CHO conditions in exercise
      performance, plasma cortisol concentration, heart rate, or core temperature. CHO
      ingestion significantly moderated the increases in leukocyte (83% in W, 28% in
      CHO; p < 0.001), monocyte (60% in W, 34% in CHO; p < 0.05), and granulocyte
      counts (120% in W, 30% in CHO; p < 0.001), but not in lymphocyte count (41% in W,
      25% in CHO). CONCLUSIONS: The increases in leukocyte and subset counts during
      moderate-intensity exercise under heat stress may be comparable to those observed
      during intense exercise in cool conditions. The response of immune cell counts is
      blunted by CHO intake during moderate-intensity exercise in the heat, and may not
      occur through the cortisol pathway.

PMID- 16110688
TI  - Computer modeling of acceleration effects on cerebral oxygen saturation.
AB  - INTRODUCTION: Failure to effectively regulate BP and cerebral perfusion during
      high-G aircraft maneuvering may contribute to reduced performance in pilots due
      to the fact that perfusion to the peripheral cerebral tissues may not be adequate
      to support the mental demands of flight. Therefore, a critical area of
      investigation is the study of cortical tissue oxygenation responses to +Gz
      acceleration. METHODS: Two experiments were used to build two sections of a
      cerebral oxygen saturation (rSo2) model. Experiment 1: Six subjects participated
      in the study. A cerebral oximeter (gold standard) provided rSo2. Acceleration
      profiles (subjects relaxed) included a 0.1 G x s(-1) G onset to central light
      loss (CLL) and a 3 G x s(-1) onset to a G level that was 1 Gz above CLL to an
      endpoint of G-LOC. Experiment 2: There were 12 subjects (with G protection) who
      participated in this study. The rSo2 data were collected during five different
      simulated aerial combat maneuvers. A model was created that read the Gz profile
      as input and calculated changes in rSo2. The correlation coefficient, linear best
      fit slope, and mean percent error were calculated to determine agreement.
      RESULTS: The average value for the correlation coefficients, linear best-fit
      slopes, and mean percent errors for the unprotected subjects were 0.79, 0.87, and
      6.08, respectively. These values for the protected subjects were 5 G (0.994,
      1.011, 0.384), 6 G (0.994, 0.909, 0.811), 7 G (0.986, 1.061, 0.692), 8 G (0.969,
      1.016, 1.300), and 9 G (0.994, 0.979, 0.558), respectively. DISCUSSION: The model
      is a good predictor of rSo2 values for protected and unprotected subjects under
      +Gz stress.

PMID- 16110689
TI  - AVP response to LBNP is attenuated in a hyperbaric environment.
AB  - INTRODUCTION: Accumulated evidence indicates attenuated vasopressin (AVP) release
      associated with hyperbaria in humans. The present study was designed to test the
      hypothesis that plasma AVP response to central hypovolemia was attenuated in a
      hyperbaric environment. METHODS: Response of AVP to central hypovolemic stress,
      in the form of lower-body negative pressure (LBNP), was measured in 10 men at 1
      and 3 atmosphere absolute (ATA) air. The stress consisted of 4 min each of
      control and LBNP at -20 and -40 mmHg. Plasma AVP, plasma norepinephrine (NE),
      plasma osmolality, and hematocrit (Hct) were measured. Thoracic impedance (Z0),
      and leg volume were also determined. RESULTS: The baseline AVP (0.9 +/- 0.3 pg x
      ml(-1)) at 1 ATA increased significantly in response to -40 mmHg LBNP (1.8 +/-
      0.6 pg x ml(-1)), but the increase was attenuated at 3 ATA (1.2 +/- 0.8 pg x ml(
      1)). The baseline NE at 3 ATA was lower by 22.4 pg x ml(-1) than that of 1 ATA
      (226.5 pg x ml(-1)). NE increased with increasing LBNP at both environmental
      pressures, but the increase was independent of the pressure. Changes in Z0,
      reflecting thoracic blood volume, were identical in both environments. Mean
      arterial pressure, plasma osmolality, and Hct remained constant throughout the
      experimental period. Leg volume increased stress dependently during LBNP
      (approximately 34 ml at -20 mmHg; approximately 74 ml at -40 mmHg) and the
      increment was similar in the two environments. CONCLUSION: The present study
      revealed that hyperbaria attenuated the response of AVP and NE to hypovolemic
      stress. The attenuated AVP response to LBNP was associated with neither plasma
      osmolality nor intrathoracic blood shift.

PMID- 16110690
TI  - Physical and cognitive performance during long-term cold weather operations.
AB  - BACKGROUND: Physiological responses, physical performance, and cognitive
      performance were measured during military cold weather survival courses to
      determine the effects of long-term cold exposure on training safety and potential
      survival ability. METHODS: There were 28 males, from 5 9-d winter survival
      courses, who participated. Cognitive performance was evaluated through logical
      reasoning, planning, and vigilance. Physical performance was evaluated with tests
      of hand function and arm strength. Subjective cold sensation scale (CSS), rating
      of perceived exertion (RPE), and mood indicators were quantified. Core
      temperature (T(core0) and HR were recorded continuously throughout the courses,
      and fingertip temperature (T(finger)) was also recorded during testing.
      Hematocrit values to indicate hydration status were obtained from blood samples
      taken on three occasions. RESULTS: Mean air temperature (T(air)) during the
      testing periods ranged from -24.4 to 4.4 degrees C among the five courses.
      Hydration level and T(core) remained normal throughout all courses while
      T(finger) decreased with decreasing T(air). Finger dexterity deteriorated by 23
      28% when T(finger) decreased from 18 to 10 degrees C. Muscular strength was
      decreased by a small (4%) but significant amount over 6 d of testing. Cognitive
      function was unaffected by cold air or time on the course. Mood indicators were
      consistent with CSS and RPE scores. CONCLUSION: Under the exposure conditions and
      availability of basic survival equipment, including water, described herein, and
      in the absence of trauma, healthy fit individuals can participate in this
      military training without any serious decrements in cognitive and physical
      performance. In an actual survival situation, similarly decreased dexterity may
      adversely affect survival activities.

PMID- 16110691
TI  - Body fluid regulation in a simulated disabled submarine: effects of cold, reduced
      O2, and elevated CO2.
AB  - INTRODUCTION: Survivors awaiting rescue aboard a disabled submarine (DISSUB)
      lacking power and/or environmental control would potentially be exposed to cold
      and reduced O2 and elevated CO2 levels. We hypothesized that elevated CO2 levels
      would lead to hormone changes that would mitigate cold and hypoxia-induced body
      fluid losses. METHODS: Blood was drawn from seven men on three mornings: baseline
      (21% O2, 0.05% CO2), after 4 d of low O2, cold, and high CO2 (T101; 4 degrees C,
      16.75% O2, 2.5% CO2), and following acute withdrawal of cold and high CO2 (T173,
      16.75% O2, 0.05% CO2). Total body water (TBW) was measured using deuterium oxide
      dilution at baseline and at T148. Hormone analyses included atrial natriuretic
      peptide (ANP), aldosterone (ALDO), and plasma renin activity (PRA). RESULTS: TBW
      decreased by 0.4 +/- 0.4 L. Water turnover was 3.0 +/- 0.5 L x d(-1). ANP (pg x
      ml(-1)) was lower (p < 0.05) at T101 (3.46 +/- 1.17) and T173 (4.97 +/- 2.28) vs.
      baseline (8.19 +/- 3.40). PRA (pg x ml(-1)) was higher (p < 0.05) at T101 (10.43
      +/- 4.90) and T173 (14.23 +/- 4.48) vs. baseline (6.81 +/- 3.43). ALDO, serum
      osmolality, and electrolytes were not different across time. Urine flow was lower
      at T101 and T173 vs. baseline, and urine osmotic clearance was lower at T173 vs.
      baseline. Free water clearance did not change across time. DISCUSSION: These data
      indicate that the combination of cold, low O2, and high CO2 for 5-7 d did not
      change total body water and hormone changes and urinary measures across the
      DISSUB were consistent with fluid retention.

PMID- 16110692
TI  - Anti-diuretic for operational aircrew: effects of desmopressin on urine flow,
      cognition, and sleepiness.
AB  - INTRODUCTION: Air operations may demand missions of many hours, and aircrew may
      experience significant discomfort due to bladder distension. Attention has been
      given to the use of in-flight urination devices, but an alternative strategy
      could be reduction of urine flow by an anti-diuretic. In this event it would be
      important to establish an effective dose range free of adverse effects. METHODS:
      The effects of desmopressin (0.05, 0.10, 0.15, and 0.20 mg) on cognitive
      performance and sleepiness (multiple sleep latency test) from 1 to 11 h, and on
      urine flow up to 24 h after drug ingestion at 09:00, were studied in 20 healthy
      young volunteers. The study was double blind, placebo controlled, and with a
      randomized five-way crossover design. RESULTS: There was no evidence of impaired
      performance with desmopressin at or below 0.15 mg. All doses reduced urine flow
      up to 12 h after drug ingestion (p < 0.001), and the reduction appeared to be
      maximal at 0.10 mg. The dose range was free of adverse effects, except for the
      possibility of headaches, but they are unlikely to be of operational
      significance. DISCUSSION: Desmopressin could prove to be a significant advance in
      the management of urinary flow in operational aircrew. The dose could be as low
      as 0.05 mg with the option to use 0.10 mg in those less sensitive to the drug.
      Individual experience of the effect of the drug would be appropriate before use
      in flight, and guidelines concerning fluid intake would be needed. Further
      information may be required for use of the drug overnight.

PMID- 16110693
TI  - Scopolamine patch to prevent seasickness: clinical response vs. plasma
      concentration in sailors.
AB  - INTRODUCTION: Scopolamine is highly effective for the treatment of seasickness.
      Nevertheless, transdermal therapeutic system (TTS) scopolamine, despite high
      compliance on the part of persons treated by the drug, fails to provide
      protection against seasickness in 26-38% of patients. To the best of our
      knowledge, the correlation between scopolamine levels in plasma and its
      therapeutic effect under sailing conditions in the open sea is investigated for
      the first time in the present study. METHODS: Subjects were 61 crewmembers of
      naval vessels treated by TTS scopolamine. The therapeutic response at sea was
      documented by questionnaire. During a period ashore, a TTS scopolamine patch was
      applied in the same subjects. Blood samples were taken and an adverse effects
      questionnaire completed 8 h after scopolamine patch application. Scopolamine
      levels were determined using an established radio-receptor assay procedure. To
      verify the reproducibility of these measurements, blood samples were taken twice
      from most subjects, on separate days after different patch applications. Subjects
      were divided into "responders," who reported at least a moderate decrease in
      seasickness severity compared with their previous experience at sea without TTS
      scopolamine therapy, and "non-responders," who had only slight symptomatic relief
      or no relief at all. RESULTS: The mean scopolamine concentration in the plasma of
      the 37 responders (156.77 +/- 77.03 pg x ml(-1)) was significantly higher than
      the mean level in the 24 non-responders (97.03 +/- 73.34 pg x ml(-1); p = 0.005,
      simple t-test). CONCLUSIONS: Attempts to increase scopolamine levels in plasma by
      increasing the drug dosage or improving transdermal absorption should be
      considered for the treatment of "non-responders".

PMID- 16110694
TI  - Automated determination of bubble grades from Doppler ultrasound recordings.
AB  - INTRODUCTION: One of the difficulties in the development of automated algorithms
      for the detection of bubbles in Doppler ultrasound recordings is that expert
      labels are only available on an aggregate basis, i.e., the expert provides a
      single label for a recording which may contain many bubbles. It is thus very
      difficult to determine whether an algorithm is correctly identifying the actual
      bubbles or simply identifying the correct number of events, but mislabeling some
      events that are not due to bubbles. METHODS: The analysis presented here shows
      that the classification probabilities for the detection of bubble events and
      other artifacts can be determined if a large number of recordings are available.
      DISCUSSION: Using a half-integer scoring system from 0-4 gives a bias of
      approximately 1-2% and a standard deviation that varies with the number of event
      sequences available, dropping from approximately 7.5% for 100 60-s recordings to
      3% for 1000 60-s recordings. These values are larger if an integer scoring system
      is used, but using a scale finer than half-integers confers no extra benefit due
      to the fact that the expert labels the whole recording rather than individual
      bubbles. CONCLUSIONS: It is thus possible to estimate the classification
      probabilities with a reasonably high degree of accuracy, but difficult to show
      that one bubble detection algorithm is superior to another to any degree of
      statistical significance. Expert labels can be used to validate, but not to
      compare the performance of bubble detection algorithms.

PMID- 16110695
TI  - Decompression sickness during simulated extravehicular activity: ambulation vs.
      non-ambulation.
AB  - BACKGROUND: Extravehicular activity (EVA) is required from the International
      Space Station on a regular basis. Because of the weightless environment during
      EVA, physical activity is performed using mostly upper-body movements since the
      lower body is anchored for stability. The adynamic model (restricted lower-body
      activity; non-ambulation) was designed to simulate this environment during
      earthbound studies of decompression sickness (DCS) risk. DCS symptoms during
      ambulatory (walking) and non-ambulatory high altitude exposure activity were
      compared. The objective was to determine if symptom incidences during ambulatory
      and non-ambulatory exposures are comparable and provide analogous estimates of
      risk under otherwise identical conditions. METHODS: A retrospective analysis was
      accomplished on DCS symptoms from 2010 ambulatory and 330 non-ambulatory
      exposures. RESULTS: There was no significant difference between the overall
      incidence of DCS or joint-pain DCS in the ambulatory (49% and 40%) vs. the non
      ambulatory exposures (53% and 36%; p > 0.1). DCS involving joint pain only in the
      lower body was higher during ambulatory exposures (28%) than non-ambulatory
      exposures (18%; p < 0.01). Non-ambulatory exposures terminated more frequently
      with non-joint-pain DCS (17%) or upper-body-only joint pain (18%) as compared
      with ambulatory exposures, 9% and 11% (p < 0.01), respectively. DISCUSSION: These
      findings show that lower-body, weight-bearing activity shifts the incidence of
      joint-pain DCS from the upper body to the lower body without altering the total
      incidence of DCS or joint-pain DCS. CONCLUSIONS: Use of data from previous and
      future subject exposures involving ambulatory activity while decompressed appears
      to be a valid analogue of non-ambulatory activity in determining DCS risk during
      simulated EVA studies.

PMID- 16110696
TI  - Crash-resistant fuel system effectiveness in civil helicopter crashes.
AB  - BACKGROUND: Crash-resistant fuel systems (CRFS) have demonstrated close to 100%
      effectiveness in survivable crashes of Army helicopters, but the technology has
      been slow to transfer into the civil helicopter arena. Federal standards for
      civil helicopter CRFS are less stringent than those for military helicopters. A
      reduction in standards for CRFS in military helicopters is being considered.
      OBJECTIVE: The goal of this study was to determine whether crashes of civil
      helicopters with CRFS are less likely to result in post-crash fire than crashes
      of those without. METHOD: Crashes of civil helicopters during 1982-2004 were
      analyzed, comparing Bell 206 helicopters manufactured with CRFS with Aerospatial
      350 helicopters manufactured during the same period (post-1981), but lacking
      CRFS. Bell 206 helicopters with CRFS were also compared with earlier models
      without CRFS. RESULTS: The highest proportion of crashes with post-crash fires
      (11.3%) was in AS-350s manufactured after 1981 (non-CRFS), and the lowest (3.7%)
      was in Bell 206s (with CRFS) [unadjusted risk ratio (RR) = 3.3, 95% confidence
      interval (CI) = 1.04, 10.50; adjusted for light and weather, RR = 2.81, Cl =
      0.82, 9.69]. Earlier models of Bell 206s without CRFS had higher risk of post
      crash fire than post-1981 models with CRFS (7.4% vs. 3.7%; adjusted RR = 2.11, Cl
      = 0.82, 5.45). CONCLUSIONS: The results of this study suggest a better
      performance, in terms of post-crash fire prevention, of CRFS-equipped civil
      helicopters as compared with those without CRFS. It is possible that CRFS in
      civil helicopters have not achieved the same degree of effectiveness as CRFS in
      military helicopters. CRFS should be used more widely in civil helicopters. The
      more stringent CRFS requirements for military helicopters should not be reduced
      without further research.

PMID- 16110697
TI  - Glaucoma pharmacotherapy: implications for flying fitness.
AB  - The objective of lowering the intraocular pressures remains the main-stay of
      therapy in the management of glaucoma, and may be achieved by medication, laser,
      or surgery. For many years the pharmacotherapy available, while quite effective,
      were few in number; principally timolol, pilocarpine, and oral acetazolamide.
      Through extensive research in glaucoma treatment, ophthalmologists now have
      access to a dozen different medications to treat glaucoma. This has invariably
      led to a decrease in the need for laser or surgery to control the intraocular
      pressures, and the number of glaucoma operations performed has progressively
      declined over the past few years. However, aviation medicine practitioners need
      to be aware of the potential adverse effects of these medications as some of
      these undesirable side effects may render the drugs unsuitable for aircrew.

PMID- 16110698
TI  - Hypoxia symptoms reported during helicopter operations below 10,000 ft: a
      retrospective survey.
AB  - INTRODUCTION: During routine aviation medicine training, rotary-wing aircrew are
      instructed that the impact of hypoxia on them from flying in unpressurized cabins
      up to 10,000 ft (3048 m) above mean sea level (AMSL) is relatively small and has
      few implications for aviation safety. Such reassurance is based on data derived
      from experiments conducted on resting subjects and may not reflect the true
      impact of hypoxia in aircrew engaged in operational tasks. METHOD: A survey
      listing common symptoms of hypoxia was distributed to Australian Army helicopter
      aircrew who had operated at altitudes up to 10,000 ft AMSL. RESULTS: There were
      53 surveys that were returned (71% response), representing 25 loadmasters, 23
      pilots, and 5 aircrewman technicians. All respondents were Australian Army
      aircrew. One or more symptoms consistent with hypoxia were reported by 86.6% of
      non-pilot aircrew and 60.9% of pilots. 60% of non-pilot aircrew reported four or
      more symptoms, compared with only 17% of pilots. The most commonly reported
      symptoms were difficulty with calculations (45%), feeling light-headed (38%),
      delayed reaction time (38%), and mental confusion (36%). Loadmasters reported
      more symptoms (mean 5.4) than pilots (mean 2.2) (p < 0.001). From the narratives
      provided (n = 21), aircrew experienced potentially operationally significant
      symptoms at a mean altitude of 8462 ft (2579 m). CONCLUSION: The helicopter
      aircrew surveyed reported symptoms consistent with hypoxia at altitudes within
      the so-called physiological zone; loadmasters reported more effects than pilots.
      It may be inappropriate to emphasize the benign nature of the physiological zone
      during aviation medicine training of a non-resting population such as helicopter
      aircrew.

PMID- 16110699
TI  - Aviation medicine in the United Kingdom: cold war and peace dividend, 1946-2000.
AB  - This is the third of three brief papers that summarize the history of aviation
      medicine in the Royal Air Force. Unusually, at the end of the Second World War,
      British aviation medicine research did not enter a period of decline. The needs
      of the Royal Air Force during the Cold War ensured the continuing development of
      the RAF Institute of Aviation Medicine. However, reduction of the threat with the
      end of the Cold War led to the requirement for a peace dividend. British aviation
      medicine research has now entered a commercial era, competing for funding from
      industry as well as from the Royal Air Force.

PMID- 16110700
TI  - Vasopressin: neurohumoral link between nausea and motion sickness.

PMID- 16110701
TI  - Space life sciences budget crisis.

PMID- 16110702
TI  - This month in aerospace medicine history--August 2005.

PMID- 16110703
TI  - A quick and simple alternative for electronic anti-G valve control.

PMID- 16110704
TI  - CAPT Gail Hathaway's farewell remarks.

PMID- 16110705
TI  - Message from the incoming President, Col. Jim Dooley.

PMID- 16110706
TI  - Association between methodological characteristics and outcome in health
      technology assessments which included case series.
AB  - OBJECTIVES: Case series constitute a weak form of evidence for effectiveness of
      health technologies. However, for a variety of reasons, such studies may be
      included in health technology assessments. There are no clear criteria for
      assessing the quality of case series. We carried out an empirical investigation
      of the association between outcome frequency and methodological characteristics
      in a sample of health technology assessments. METHODS: Systematic reviews of
      functional endoscopic sinus surgery for nasal polyps, spinal cord stimulation for
      chronic back pain, and percutaneous transluminal coronary angioplasty and
      coronary artery bypass grafting for chronic stable angina were identified as
      containing more than forty case series. Data were extracted by one reviewer and
      checked by a second on population characteristics, outcomes, and the following
      methodological features: sample size, prospective/retrospective approach,
      consecutive recruitment, multi- or single-center organization, length of follow
      up, independence of outcome measurement, and date of publication. Association
      between methodological features and outcome were explored in univariate and
      multivariate analyses using parametric and nonparametric tests and robust
      regression or analysis of variance/analysis of covariance, as appropriate.
      RESULTS: Included reviews contained between forty-two and seventy-six case series
      studies, involving 5 to 172,283 participants. Reporting of methodological
      features was poor and limited the analyses. In general, we found little evidence
      of any association between methodological characteristics and outcome. Sample
      size is used as an inclusion criterion in many reviews of'case series but was
      consistently shown to have no relationship to outcome in all analyses. A
      prospective approach was not associated with outcome. Insufficient data were
      available to explore consecutive recruitment. Mixed results were shown for length
      of follow-up, independence of outcome measurement, and publication date.
      CONCLUSIONS: We found little evidence to support the use of many of the factors
      included in tools used for quality assessment of case series. Importantly, we
      found no relationship between study size and outcome across the four examples
      studied. Isolated examples of a potentially important relationship between other
      methodological factors and outcome were shown, for example, blinding of outcome
      measurement, but these examples were not shown consistently across the small
      number of examples studied. Further research into the determinants of quality in
      case series studies is required to support health technology assessment.

PMID- 16110707
TI  - Health needs assessment tools: progress and potential.
AB  - OBJECTIVES: Health needs has attracted the interest of policy-makers, health
      economists, and health professionals as modern health services try to satisfy
      individual and population health needs to optimize resource utilization. Health
      needs can be assessed by administering various types of survey or interview-based
      instruments. If health needs are to be satisfied in changing health agendas in
      developed and developing countries, it is essential to employ valid and reliable
      tools. Despite the importance of needs assessment, no comprehensive review of
      tools is currently available. We carried out a literature search to define and
      categorize existing health needs assessment tools. METHODS: We reviewed medical
      and social search engines for items containing specific health needs-related
      words to identify needs tools across a range of specialties. Papers were reviewed
      in terms of design, subject matter, psychometric features, and method of
      administration method. RESULTS: Thirty-one employed in 52 studies including
      cancer, mental health, palliative care, multiple sclerosis, and cardiovascular
      disease tools were identified. CONCLUSIONS: This report summarizes available
      health needs instruments in a range of diseases to assist researchers in
      accessing health needs resources more easily and to encourage further research in
      this field.

PMID- 16110708
TI  - Self-reports of health-care utilization: diary or questionnaire?
AB  - OBJECTIVES: The feasibility and convergent validity of a cost diary and a cost
      questionnaire was investigated. METHODS: Data were obtained as part of a cost
      utility analysis alongside a multicenter clinical trial in patients with
      resectable rectal cancer. A sample of 107 patients from 30 hospitals was asked to
      keep a weekly diary during the first 3 months after surgery, and a monthly diary
      from 3 to 12 months after surgery. A second sample of seventy-two patients from
      twenty-eight hospitals in the trial received a questionnaire at 3, 6, and 12
      months after surgery, referring to the previous 3 or 6 months. Format and items
      of the questions were similar and included a wide range of medical and nonmedical
      items and costs after hospitalization for surgery. RESULTS: Small differences
      were found with respect to nonresponse (range, 79 to 86 percent) and missing
      questions (range, 1 to 6 percent between the diary and questionnaire). For most
      estimates of volumes of care and of costs, the diary and questionnaire did not
      differ significantly. Total 3-month nonhospital costs were 1,860 Euros, 1,280
      Euros, and 1,050 Euros in the diary sample and 1,860 Euros, 1,090 Euros, and 840
      Euros in the questionnaire sample at 3, 6, and 12 months after surgery,
      respectively (p = .50). However, with respect to open questions, the diary sample
      tended to report significantly more care. CONCLUSIONS: For the assessment of
      health-care utilization in economic evaluations alongside clinical trials, a cost
      questionnaire with structured closed questions may replace a cost diary for
      recall periods up to 6 months.

PMID- 16110709
TI  - Populating decision-analytic models: the feasibility and efficiency of database
      searching for individual parameters.
AB  - OBJECTIVES: The aim of the study was to investigate the feasibility and
      effectiveness of searching selected databases to identify information required to
      populate a decision-analytic model. METHODS: Methods of searching for information
      to populate a decision-analytic model were piloted using a case study of
      prophylactic antibiotics to prevent recurrent urinary tract infections in
      children. This study explored how the information requirements for a decision
      analytic model could be developed into searchable questions and how search
      strategies could be derived to answer these questions. The study also assessed
      the usefulness of three published search filters and explored which resources
      might produce relevant information for the various model parameters. RESULTS:
      Based on the data requirements for this case study, 42 questions were developed
      for searching. These questions related to baseline event rates, health-related
      quality of life and outcomes, relative treatment effects, resource use and unit
      costs, and antibiotic resistance. A total of 1,237 records were assessed by the
      modeler, and of these, 48 were found to be relevant to the model. Search
      precision ranged from 0 percent to 38 percent, and no single database proved the
      most useful for all the questions. CONCLUSIONS: The process of conducting
      specific searches to address each of the model questions provided information
      that was useful in populating the case study model. The most appropriate
      resources to search were dependent on the question, and multiple database
      searching using focused search strategies may prove more effective in finding
      relevant data than thorough searches of a single database.

PMID- 16110710
TI  - Toward a procedure for integrating moral issues in health technology assessment.
AB  - OBJECTIVES: Although ethics has been on the agenda in health technology
      assessment (HTA) since its inception, the integration of moral issues is still
      not standard and is performed in a vast variety of ways. Therefore, there is a
      need for a procedure for integrating moral issues in HTA. METHODS: Literature
      review of existing approaches together with application of various theories in
      moral philosophy and axiology. RESULTS: The article develops a set of questions
      that addresses a wide range of moral issues related to the assessment and
      implementation of health technology. The issues include general moral issues and
      moral issues related to stakeholders, methodology, characteristics of technology,
      and to the HTA process itself. The questions form a kind of checklist for use in
      HTAs. CONCLUSIONS: The presented approach for integrating moral issues in HTA has
      a broad theoretical foundation and has shown to be useful in practice.
      Integrating ethical issues in HTAs can be of great importance with respect to the
      dissemination of HTA results and in efficient health policy making.

PMID- 16110711
TI  - Technology assessment in dentistry: a comparison of the longevity and cost
      effectiveness of inlays.
AB  - OBJECTIVES: An example of technology assessment in dental care by evaluating the
      (cost-)effectiveness of types of three-surface inlays (gold, laboratory
      fabricated ceramic, and chairside CAD/CAM ceramic) is provided. METHODS: MEDLINE,
      EMBASE, and the Cochrane Library were searched for studies published between 1966
      and June 2003 that reported annual survival probabilities and annual
      observations. The longevity of different types of inlays was measured by the
      number of failure-free years. Annual survival rates from different studies were
      pooled by weighing the rates of each study by the inverse of the variance of the
      effect estimate. A cost-effectiveness analysis from the perspective of German
      private health insurers was performed using billing charges. RESULTS: Three,
      five, and two case series on laboratory-fabricated ceramic, chairside CAD/CAM
      ceramic, and gold inlays, respectively, were included. Over a 9-year observation
      period, the number of undiscounted failure-free years was 8.62 (95 percent
      confidence interval, 8.40-8.85), 8.65 (8.58-8.73), and 8.76 (8.72-8.80) for
      laboratory-fabricated ceramic, chairside CAD/CAM ceramic, and gold inlays,
      respectively. Laboratory-fabricated ceramic inlays were the most expensive.
      CONCLUSIONS: While laboratory-fabricated ceramic, chairside CAD/CAM ceramic, and
      gold inlays had a strikingly similar failure-free survival rate, laboratory
      fabricated ceramic inlays had the highest costs and, thus, were less cost
      effective than chairside CAD/CAM ceramic and gold inlays.

PMID- 16110712
TI  - Cost-effectiveness of drug-eluting coronary stents in Quebec, Canada.
AB  - OBJECTIVES: The aim of this investigation was to assess the incremental cost
      effectiveness of replacing bare metal coronary stents (BMS) with drug-eluting
      stents (DES) in the Province of Quebec, Canada. METHODS: The strategy used was a
      cost-effectiveness analysis from the perspective of the health-care provider, in
      the province of Quebec, Canada (population 7.5 million). The main outcome measure
      was the cost per avoided revascularization intervention. RESULTS: Based on the
      annual Quebec rate of 14,000 angioplasties with an average of 1.7 stents per
      procedure and a purchase cost of $2,600 Canadian dollar (CDN) for DES, 100
      percent substitution of BMS with DES would require an additional $45.1 million
      CDN of funding. After the benefits of reduced repeat revascularization
      interventions are included, the incremental cost would be $35.2 million CDN. The
      cost per avoided revascularization intervention (18 percent coronary artery
      bypass graft, 82 percent percutaneous coronary intervention [PCI]) would be
      $23,067 CDN. If DES were offered selectively to higher risk populations, for
      example, a 20 percent subgroup with a relative restenosis risk of 2.5 times the
      current bare metal rate, the incremental cost of the program would be $4.9
      million CDN at a cost of $7,800 per avoided revascularization procedure. Break
      even costs for the program would occur at DES purchase cost of $1,161 for 100
      percent DES use and $1,627 for selective 20 percent DES use for high-risk
      patients for restenosis (RR = 2.5). Univariate and Monte Carlo sensitivity
      analyses indicate that the parameters most affecting the analysis are the
      capacity to select patients at high risk of restenosis, the average number of
      stents used per PCI, baseline restenosis rates for BMS, the effectiveness ratio
      of restenosis prevention for DES versus BMS, the cost of DES, and the
      revascularization rate after initial PCI. Sensitivity analyses suggest little
      additional health benefits but escalating cost-effectiveness ratios once a DES
      penetration of 40 percent has been attained. CONCLUSIONS: Under current
      conditions in Quebec, Canada, selective use of DES in high-risk patients is the
      most acceptable strategy in terms of cost-effectiveness. Results of such an
      analysis would be expected to be similar in other countries with key model
      parameters similar to those used in this model. This model provides an example of
      how to evaluate the cost-effectiveness of selective use of a new technology in
      high-risk patients.

PMID- 16110713
TI  - Cost-effectiveness of pressure-relieving devices for the prevention and treatment
      of pressure ulcers.
AB  - OBJECTIVES: The cost-effectiveness of alternating pressure-relieving devices,
      mattress replacements, and mattress overlays compared with a standard hospital
      (high-specification foam mattress) for the prevention and treatment of pressure
      ulcers in hospital patients in the United Kingdom was investigated. METHODS: A
      decision-analytic model was constructed to evaluate different strategies to
      prevent or treat pressure ulcers. Three scenarios were evaluated: the prevention
      of pressure ulcers, the treatment of superficial ulcers, and the treatment of
      severe ulcers. Epidemiological and effectiveness data were obtained from the
      clinical literature. Expert opinion using a rating scale technique was used to
      obtain quality of life data. Costs of the devices were obtained from
      manufacturers, whereas costs of treatment were obtained from the literature.
      Uncertainty was explored through probabilistic sensitivity analysis. RESULTS:
      Using 30,000 pounds sterling/QALY (quality-adjusted life year) as the decision
      maker's cut off point (the current UK standard), in scenario 1 (prevention), the
      cost-effective strategy was the mattress overlay at 1, 4, and 12 weeks. In
      scenarios 2 and 3, the cost-effective strategy was the mattress replacement at 1,
      4, and 12 weeks. Standard care was a dominated intervention in all scenarios for
      values of the decision-maker's ceiling ratio ranging from 5,000 pounds sterling
      to 100,000 pounds sterling/QALY. However, the probabilistic sensitivity analysis
      results reflected the high uncertainty surrounding the choice of devices.
      CONCLUSIONS: Current information suggests that alternating pressure mattress
      overlays may be cost-effective for the prevention of pressure ulcers, whereas
      alternating pressure mattress replacements appears to be cost-effective for the
      treatment of superficial and severe pressure ulcers.

PMID- 16110714
TI  - Impact of uncertainty on cost-effectiveness analysis of medical strategies: the
      case of high-dose chemotherapy for breast cancer patients.
AB  - OBJECTIVES: The object of this study was to determine, taking into account
      uncertainty on cost and outcome parameters, the cost-effectiveness of high-dose
      chemotherapy (HDC) compared with conventional chemotherapy for advanced breast
      cancer patients. METHODS: An analysis was conducted for 300 patients included in
      a randomized clinical trial designed to evaluate the benefits, in terms of
      disease-free survival and overall survival, of adding a single course of HDC to a
      four-cycle conventional-dose chemotherapy for breast cancer patients with
      axillary lymph node invasion. Costs were estimated from a detailed observation of
      physical quantities consumed, and the Kaplan-Meier method was used to evaluate
      mean survival times. Incremental cost-effectiveness ratios were evaluated
      successively considering disease-free survival and overall survival outcomes.
      Handling of uncertainty consisted in construction of confidence intervals for
      these ratios, using the truncated Fieller method. RESULTS: The cost per disease
      free life year gained was evaluated at 13,074 Euros, a value that seems to be
      acceptable to society. However, handling uncertainty shows that the upper bound
      of the confidence interval is around 38,000 Euros, which is nearly three times
      higher. Moreover, as no difference was demonstrated in overall survival between
      treatments, cost-effectiveness analysis, that is a cost minimization, indicated
      that the intensive treatment is a dominated strategy involving an extra cost of
      7,400 Euros, for no added benefit. CONCLUSIONS: Adding a single course of HDC led
      to a clinical benefit in terms of disease-free survival for an additional cost
      that seems to be acceptable, considering the point estimate of the ratio.
      However, handling uncertainty indicates a maximum ratio for which conclusions
      have to be discussed.

PMID- 16110715
TI  - Spinal cord stimulation for failed back surgery syndrome: a decision-analytic
      model and cost-effectiveness analysis.
AB  - OBJECTIVES: The aim of this study was to develop a decision-analytic model to
      assess the cost-effectiveness of spinal cord stimulation (SCS), relative to
      nonsurgical conventional medical management (CMM), for patients with failed back
      surgery syndrome (FBSS). METHODS: A decision tree and Markov model were developed
      to synthesize evidence on both health-care costs and outcomes for patients with
      FBSS. Outcome data of SCS and CMM were sourced from 2-year follow-up data of two
      randomized controlled trials (RCTs). Treatment effects were measured as levels of
      pain relief. Short- and long-term health-care costs were obtained from a detailed
      Canadian costing study in FBSS patients. Results are presented as incremental
      cost per quality adjusted life year (QALY) and expressed in 2003 Euros. Costs
      were discounted at 6 percent and outcomes at 1.5 percent. RESULTS: Over the
      lifetime of the patient, SCS was dominant (i.e., SCS is cost-saving and gives
      more health gain relative to CMM); a finding that was robust across sensitivity
      analyses. At a 2-year time horizon, SCS gave more health gain but at an increased
      cost relative to CMM. Given the uncertainty in effectiveness and cost parameters,
      the 2-year cost-effectiveness of SCS ranged from 30,370 Euros in the base case to
      63,511 Euros in the worst-case scenario. CONCLUSIONS: SCS was found to be both
      more effective and less costly than CMM, over the lifetime of a patient. In the
      short-term, although SCS is potentially cost-effective, the model results are
      highly sensitive to the choice of input parameters. Further empirical data are
      required to improve the precision in the estimation of short-term cost
      effectiveness.

PMID- 16110716
TI  - Cost and health status analysis after autologous chondrocyte implantation and
      mosaicplasty: a retrospective comparison.
AB  - OBJECTIVES: Chondral defects of the knee cartilage are prevalent. Autologous
      chondrocyte implantation (ACI) and mosaicplasty are increasingly used to treat
      symptomatic knee defects. This study assessed the costs and health status
      outcomes after ACI and mosaicplasty. METHODS: Patients were eligible to
      participate in this cross-sectional study if they received ACI or mosaicplasty at
      the Royal National Orthopaedic Hospital between 1997 and 2001 or were on a
      waiting list for ACI. Secondary-care resource use was collected to 2 years
      postoperatively using a resource collection proforma. Participants responded to
      postal questions about sociodemographic characteristics and knee-related
      (Modified Cincinnati Knee Rating System) and general health status (EQ-5D).
      RESULTS: Fifty-three ACI, twenty mosaicplasty, and twenty-two patients waiting
      for ACI participated. The average cost per patient was higher for ACI (10,600
      pounds sterling: 95 percent confidence interval [CI], 10,036 pounds sterling
      11,214 pounds sterling) than mosaicplasty (7,948 pounds sterling: 95 percent CI,
      6,957 pounds sterling-9,243 pounds sterling). Postoperatively, ACI and
      mosaicplasty patients (combined) experienced better health status than those
      waiting for ACI. ACI patients tended to have better health status outcomes than
      mosaicplasty patients (not statistically significant). Estimated average EQ-5D
      social tariff improvements for quality-adjusted life year (QALY) calculations
      were 0.23 (ACI) and 0.06 (mosaicplasty). Average costs per QALY were 23,043
      pounds sterling (ACI) and 66,233 pounds sterling (mosaicplasty). The incremental
      cost effectiveness ratio (ICER) for providing ACI over mosaicplasty was 16,349
      pounds sterling. CONCLUSIONS: Average costs were higher for ACI than
      mosaicplasty. However, both the estimated cost per QALY and ICER for providing
      ACI over mosaicplasty fell beneath an implicit English funding threshold of
      30,000 pounds sterling per QALY. Prospective studies should include measures of
      utility to confirm the estimated cost utility ratios of ACI and mosaicplasty.

PMID- 16110717
TI  - Diagnosis of appendicitis in adults by ultrasonography or computed tomography: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: The use of ultrasonography and computed tomography (CT) in the
      diagnosis of appendicitis in adult patients was compared. METHODS: Systematic
      review and meta-analysis of current evidence in two clinical situations:
      unselected nonpregnant, adult patients with symptoms of appendicitis, and more
      selective use in only those patients who still have an equivocal diagnosis
      subsequent to routine clinical investigations. RESULTS: Meta-analysis of eligible
      studies shows CT to have better sensitivity and specificity than ultrasound in
      both clinical situations. CONCLUSIONS: Application of these findings in clinical
      practice and/or policy would need to evaluate the better diagnostic performance
      of CT against its cost and availability. In addition, it is imperative that
      future studies be conducted in patient populations that are well-defined with
      respect to prior investigations. Sequelae of false-negative and false-positive
      diagnoses should also be evaluated.

PMID- 16110718
TI  - Effects of continuing medical education on improving physician clinical care and
      patient health: a review of systematic reviews.
AB  - OBJECTIVES: The objective of physician continuing medical education (CME) is to
      help them keep abreast of advances in patient care, to accept new more-beneficial
      care, and discontinue use of existing lower-benefit diagnostic and therapeutic
      interventions. The goal of this review was to examine effectiveness of current
      CME tools and techniques in changing physician clinical practices and improving
      patient health outcomes. METHODS: Results of published systematic reviews were
      examined to determine the spectrum from most- to least-effective CME techniques.
      We searched multiple databases, from 1 January 1984 to 30 October 2004, for
      English-language, peer-reviewed meta-analyses and other systematic reviews of CME
      programs that alter physician behavior and/or patient outcomes. RESULTS: Twenty
      six reviews met inclusion criteria, that is, were either formal meta-analyses or
      other systematic reviews. Interactive techniques (audit/feedback, academic
      detailing/outreach, and reminders) are the most effective at simultaneously
      changing physician care and patient outcomes. Clinical practice guidelines and
      opinion leaders are less effective. Didactic presentations and distributing
      printed information only have little or no beneficial effect in changing
      physician practice. CONCLUSIONS: Even though the most-effective CME techniques
      have been proven, use of least-effective ones predominates. Such use of
      ineffective CME likely reduces patient care quality and raises costs for all, the
      worst of both worlds.

PMID- 16110719
TI  - Decision making in general practice: the availability and use of a specific
      laboratory analysis.
AB  - OBJECTIVES: The aim of this investigation was to study the effect of general
      practitioners' (GP's) characteristics on two decisions: whether to have the
      Helicobacter pylori rapid test (HPRT) in the office laboratory and whether to use
      this test or a similar hospital-based serological test in a typical clinical
      situation described in a vignette. METHODS: Discrete choice analysis with binary
      logit models were used to predict the probability that a general practice has the
      HPRT, as well as the GP's probability of using the HPRT or a similar test in this
      clinical situation. RESULTS: We found that the number of consultations per week
      has a positive effect on the probability of having the HPRT, indicating that the
      size of the practice affects the decision to have such a test in the repertoire.
      Furthermore, four variables significantly increased the probability of using one
      of the lab tests: more if located in urban practices, more by solo practitioners,
      more when the GP stated a high probability for H. pylori associated disease, and
      more when the GP had the rapid test available in the practice. In our analysis,
      the remuneration system is endogenous and does not have a significant effect on
      the two decisions. CONCLUSIONS: Our study demonstrates that characteristics of
      the GP affect the availability and use of a specific laboratory analysis.

PMID- 16110720
TI  - Test-retest reliability of health utilities index scores: evidence from hip
      fracture.
AB  - OBJECTIVES: There is relatively little evidence on the test-retest reliability of
      utility scores derived from multiattribute measures. The objective was to
      estimate test-retest reliability for Health Utilities Index Mark 2 (HUI2) and
      Mark 3 (HUI3) utility scores in patients recovering from hip fracture. METHODS:
      We enrolled an inception cohort of hip fracture patients within 3 to 5 days of
      surgery. Baseline assessments included the Functional Independence Measure (FIM),
      Folstein Mini-Mental State Examinations, and the HUI2 and HUI3 questionnaire.
      Follow-up assessments at 1, 3, and 6 months also included a global change
      question. Test-retest reliability was assessed as agreement between 3- and 6
      month scores using the intraclass correlation coefficient (ICC). Two approaches
      were used to classify patients as stable; a third approach based on the
      generalizability theory was also used. Patients were classified as stable if
      their FIM overall scores changed by 10 points or fewer and if they classified
      themselves as having experienced no or only a little change according to their
      global change question. RESULTS: Complete data at both the 3- and 6-month
      assessments based on self-report were available for 196 patients; 141 patients
      with complete data were classified as stable. The ICCs for HUI2 and HUI3 for
      stable patients were 0.71 and 0.72; the ICCs derived from the generalizability
      theory were 0.76 and 0.77. CONCLUSIONS: Test-retest reliability for HUI in this
      cohort was similar to reliability estimates for other preference-based
      multiattribute and generic health-profile measures--in the acceptable range for
      making valid group-level comparisons.

PMID- 16110721
TI  - Diffusion of published cost-utility analyses in the field of health policy and
      practice.
AB  - OBJECTIVES: The diffusion of cost-utility analyses (CUAs) through the medical
      literature was examined, documenting visible patterns and determining how they
      correspond with expectations about the diffusion of process innovations. METHODS:
      This study used 539 CUAs from a registry. It includes data elements comprising
      year of publication, the research center in which the study was performed, the
      clinical area covered by the CUA, and the specific journal. Finally, each paper
      was assigned to a journal type that could be one of the three categories: health
      services research, general medicine, or clinical specialty. RESULTS: When the
      average number of publications is plotted against time, the plot reveals an S
      shaped curve. It appears that, whereas CUAs initially were published more
      frequently in general medical or health services research journals, there was a
      clear increase in the diffusion of CUA into subspecialty journals over time. The
      concentration ratio for research centers as measured by the Herfindhal-Hirschman
      Index decreased over time. CONCLUSIONS: The spread of CUA through the medical
      literature follows patterns identified for the diffusion of other new
      technologies and processes. Future research should focus on what impact this
      spread has had on the practice of medicine and formulation of health policy.

PMID- 16110722
TI  - Cluster randomized trials: another problem for cost-effectiveness ratios.
AB  - OBJECTIVES: This work has investigated under what conditions cost-effectiveness
      data from a cluster randomized trial (CRT) are suitable for analysis using a
      cluster-adjusted nonparametric bootstrap. The bootstrap's main advantages are in
      dealing with skewed data and its ability to take correlations between costs and
      effects into account. However, there are known theoretical problems with a
      commonly used cluster bootstrap procedure, and the practical implications of
      these require investigation. METHODS: Simulations were used to estimate the
      coverage of confidence intervals around incremental cost-effectiveness ratios
      from CRTs using two bootstrap methods. RESULTS: The bootstrap gave excessively
      narrow confidence intervals, but there was evidence to suggest that, when the
      number of clusters per treatment arm exceeded 24, it might give acceptable
      results. The method that resampled individuals as well as clusters did not
      perform well when cost and effectiveness data were correlated. CONCLUSIONS: If
      economic data from such trials are to be analyzed adequately, then there is a
      need for further investigations of more complex bootstrap procedures. Similarly,
      further research is required on methods such as the net benefit approach.

PMID- 16110723
TI  - Validity of original studies in health technology assessment reports:
      significance of standardized assessment and reporting.
AB  - OBJECTIVES: As health technology assessments (HTA) may have considerable impact
      on health-care decisions, it is essential to guarantee the expected quality of
      these assessments. Variations in the methods used or lack of transparency can
      affect the important role of HTA reports. METHODS: In our study, we analyzed the
      methods used in two corresponding HTA reports to assess the validity of two key
      papers, which were included in both reports. Also the discussions and the final
      conclusions of both reports were compared. RESULTS: The authors of the two HTA
      reports used different instruments to assess the validity of the original
      studies. A minor problem is differences that were found in the assessments of
      identical validity aspects of the included studies and in the information
      provided in the HTA reports. A more serious problem was found in both HTA reports
      which identified the weakness of the key papers and expressed these limitations
      in the discussions (read mainly by scientists) but not in the conclusions (read
      mainly by policy-makers). CONCLUSIONS: The results of this study may be important
      for any institution that prepares recommendations for policy-makers. In the case
      of HTA reports, no new checklists are necessary as the checklist offered by the
      INAHTA contains the needed information. It may be necessary, however, to consider
      an "intramural quality board," which helps the member organizations guarantee
      both the transparency of the original studies included in HTA reports and the
      transparency of the HTA report itself.

PMID- 16110724
TI  - When analyses are invalidated by erroneous assumptions.

PMID- 16110725
TI  - Health-care management and the culture of assessment: an urgent liaison?

PMID- 16110726
TI  - The evolution of research on disability in old age.

PMID- 16110727
TI  - Muscle weakness and imbalance in older dizzy patients.
AB  - BACKGROUND AND AIMS: Dizziness is common in older adults, and may be associated
      with limitations in physical performance. The purpose of this study was to
      investigate if leg muscle weakness and imbalance exist in older dizzy patients.
      METHODS: Twenty-three older dizzy patients and an age-matched group of 16 healthy
      non-dizzy older adults participated in the study. Isometric strength of leg
      muscles, center of pressure (COP) during quiet standing, and maximal distance of
      reaching forward in standing were tested. All patients answered the Dizziness
      Handicap Inventory (DHI). RESULTS: Most patients reported that they were
      handicapped by dizziness (DHI mean 31.8, SD 22.1). Compared with the healthy
      group, they showed significantly weaker strength in hip extension, knee extension
      and ankle dorsiflexion (all p < 0.000). Imbalance, indicated by greater COP
      trajectory (p = 0.008) and anteroposterior range of displacement (p = 0.001)
      during quiet standing, and a smaller forward reach distance (p < 0.000), was also
      found in patients. CONCLUSIONS: Leg muscle weakness and imbalance were more
      common in older dizzy patients than in healthy subjects. Clinical management
      should include assessment and therapy for these problems.

PMID- 16110728
TI  - Effects of a partially supervised training program in subjects over 75 years of
      age.
AB  - BACKGROUND AND AIMS: Partially supervised training programs may be preferable
      than class-based ones in older subjects because the adherence rate is more likely
      to be good and they cost less. The main purpose of this investigation was to
      provide some evidence of the effectiveness of a 4-month partially supervised
      training program. We compared it with a class-based program focusing on the knee
      extensor (KE) and ankle plantar flexor (APF) muscles. METHODS: We selected for
      the study 14 subjects over 75 years of age (75+), age range 75 to 83 years with a
      mean age of 77.8, and 14 subjects over 65 years of age (65+), age range 65 to 72
      years, mean age 66.3 years. They were moderately physically active subjects, free
      from neurological, cardiovascular, metabolic or inflammatory diseases. The two
      groups underwent two 4-month training sessions 3 days a week, including: warm-up,
      aerobics, strength training, cool-down exercises. 65+ subjects underwent a class
      based program three times a week. 75+ subjects underwent a partially supervised
      program consisting of two supervised sessions and one session at home. Strength
      training was carried out bilaterally with the "Leg Press" and "Sitting Calf"
      variable-resistance machines (Technogym, Italy). The subjects performed one set
      of 10 repetitions with a 2-min rest in between. At home, 75+ subjects were
      instructed to carry out the strength exercises with graded elastic bands
      (Theraband). Subjects were tested immediately before and after the 4-month
      training. In addition to weight-lifting ability (1RM), we measured the isometric
      maximum strength values of KE and APF with a Cybex Norm dynamometer at various
      angles. RESULTS: Significant baseline differences between 75+ and 65+ were found
      at all KE angles except 30 degrees and -20 degrees APF. A significantly increased
      maximum load (1RM) was observed over the 4-month period. The baseline and post
      training torque-angle relationships for APF and KE in the two groups showed
      higher post-training gains in 75+ at all angles except at -20 degrees APF,
      although a statistically significant difference (p < 0.005) between the groups
      was only found at 30 degrees KE. CONCLUSION: Our baseline data confirm the decay
      in torque capacity in subjects aged 75+ compared with 65+. The partially
      supervised training for 75+ subjects showed better responses in terms of relative
      strength gain than for 65+ subjects, and it appears effective in counteracting
      the age-related physiological and functional decay which appears to be
      particularly evident around that age.

PMID- 16110729
TI  - Concurrent and predictive validity of "getting up from lying on the floor".
AB  - BACKGROUND AND AIMS: Older age, higher morbidity and lower functional capacity
      are associated with fall injuries. Inability to get up from the floor is
      associated with older age, higher morbidity and lower functional capacity. The
      purpose of this study was to assess the concurrent and predictive validity of the
      ability of elderly women to get up from lying on the floor. METHODS: In a random
      sample of 307 women aged 75 years and over (mean 80.8 years, response rate 74.5%)
      living in the community, baseline registrations of ability to get up from lying
      on the floor, health and function were recorded. Serious fall injuries during the
      subsequent year served as the outcome. RESULTS: 240 (78.2%) managed to get up
      independently. The highest independent association was with items primarily
      related to mobility, e.g., ability to climb steps and performance on the Timed Up
      & Go test (TUG). However, arthrosis of the hip and difficulty with walking
      indoors were among the variables independently associated with the ability to get
      up from lying on the floor. During the follow-up year, 50.5% experienced falls,
      of which one in four resulted in serious injury and one in eight in a fracture.
      The ability to get up from lying on the floor was a significant predictor of
      serious fall-related injury (OR 2.1). Among those who experienced a fall, the
      risk of injury was markedly higher for those unable to rise (OR 3.7). The
      positive predictive value of being unable to rise for serious injury was 0.30,
      indicating that nearly one out of three of the elderly women with such problems
      are predicted to experience a serious fall-related injury during the following 12
      months. CONCLUSIONS: The test "get up from lying on the floor" is a marker of
      failing health and function in the elderly and a significant predictor of serious
      fall injuries.

PMID- 16110730
TI  - An algorithm to screen long-term care residents at risk for accidental falls.
AB  - BACKGROUND AND AIMS: The process applied to identify fall risks in frail elderly
      persons remains a matter of debate. We intended to develop a fall screening
      instrument for clinically defined subgroups of long-term care residents, to be
      administered by nursing staff. METHODS: Fall risk indicators were selected by
      multiple logistic regression in three pre-defined subgroups. The first consisted
      of residents who were not able to transfer, defined as a change from sit-to-stand
      position, without physical assistance (NAT). The second subgroup comprised
      residents who were able to transfer, but who had had a recent fall during the
      last 6 months (AT-F). Residents who were able to transfer but had had no recent
      fall (AT-NF) were in the third subgroup. The prospective observational study
      included 472 long-stay residents (mean age 84 years, 79% female) from three
      community nursing homes, with a follow-up period of 12 months. RESULTS: Fall
      incidence was highest in the AT-F subgroup: 6066 per 1000 resident years. The
      risk indicators identified included a positive fall history and restraint use in
      the NAT group, transfer assistance in the AT-F group, and urinary incontinence
      and visual impairment in the AT-NF group. CONCLUSIONS: The identification of
      different risk indicators in the subgroups indicates that specific strategies may
      be more appropriate to improve the effectiveness of fall prevention in long-term
      care, than the application of one strategy to all residents. The identification
      of incontinence, visual impairment, and restraints as risk indicators stresses
      the need for intervention studies which specifically address these items.

PMID- 16110731
TI  - Evaluation of continuous summary physical performance scores (CSPPS) in an
      elderly cohort.
AB  - BACKGROUND AND AIMS: Physical performance is an important predictor of quality of
      life among the elderly. A valid and sensitive measure of physical performance is
      needed in order to evaluate possible interventions. The aim of this study was to
      examine the validity and reliability of the Continuous Summary Physical
      Performance Score (CSPPS) and its relationship to the Quartile Summary Physical
      Performance Score (QSPPS). METHODS: This cross-sectional study of an elderly
      cohort from 5 centers in the US and Europe included men and women (> age 65)
      reporting at least two domains of disability. Subjects completed assessments of
      mobility and ability to perform activities of daily living (ADLs), the physical
      component of the SF-36, and a self-rating of physical performance. Timed physical
      performance tests were used to calculate the CSPPS and QSPPS. RESULTS: 216
      subjects took part (mean age = 81 years). The distribution of CSPPS scores was
      similar for men and women, with a mean of 59.2 (SD 17.8), median of 64.3, and
      range from 1.3 to 91. Subjects with older age, higher degree of disability, and
      lower self-rated physical performance had lower CSPPS scores. The CSPPS had good
      test-retest reliability (r = 0.92), and CSPPS and QSPPS are highly correlated (r
      = 0.94, p < 0.001). However, the QSPPS appears to lack the linearity, and the
      ranges of the CSPPS for each score of the QSPPS overlap substantially.
      CONCLUSIONS: In a cohort with moderate to severe disability, the CSPPS appears to
      be a valid, reproducible measure that can discriminate smaller yet clinically
      meaningful differences in physical function, as compared with the QSPPS.

PMID- 16110732
TI  - Relationships between leisure-time physical activity, obesity and disability in
      elderly men.
AB  - BACKGROUND AND AIMS: Relationships have already been shown between leisure-time
      physical activity, obesity and body composition in young adults. However, this
      association needs to be confirmed in the elderly. The aim of this study was to
      investigate the relationship between leisure-time physical activity, obesity,
      preservation of muscle mass and disability in elderly men. METHODS: Cross
      sectional analysis of a sample of 85 community-dwelling men, 68 to 79 years of
      age. Body mass index (BMI) was used to quantify obesity. Body composition was
      evaluated using Dual Energy X-ray Absorptiometry. Disability was measured using a
      modified version of the Activities of Daily Living scale. Leisure-time physical
      activity was evaluated by a validated self-administered questionnaire. RESULTS: A
      negative relation between obesity and weekly walking was observed. Walking less
      than 30 minutes per day was associated with a 2.7 greater probability of being
      obese (95% CI 1.1-6.7). High-intensity exercise, such as brisk walking or
      gardening, was inversely correlated with body fat (R = -0.296, p < 0.01) and
      directly correlated with appendicular skeletal mass (R = 0.238, p < 0.05). The
      prevalence of disability was the highest (58%) among overweight elderly subjects
      at the lowest tertile of exercise. Multiple logistic regression selected BMI as a
      positive predictor and high-intensity exercise as a negative predictor of
      disability. CONCLUSIONS: Our study shows that, in elderly men, leisure-time
      physical activity is inversely associated with body fat, BMI, and reported
      disability, but positively associated with appendicular fat-free mass. The
      highest prevalence of reported disability was observed in sedentary subjects with
      BMI higher than 25 kg/m2.

PMID- 16110733
TI  - Movement time and aging: a normative study in healthy subjects with the "Movement
      Time Analyzer".
AB  - BACKGROUND AND AIMS: Parkinson's disease (PD) is one of the most frequent
      neurodegenerative disorders characterized by bradykinesia, tremor at rest, and
      rigidity. Movement Time (MT) has been investigated in PD to evaluate bradykinesia
      and its levodopa-induced modifications. The Movement Time Analyzer (MTA) is a
      simple, objective and reliable instrument to study MT, but no normative study has
      been reported to date. METHODS: In a sample of normal subjects (n = 68), we
      studied MT detected by MTA in order to assess normative values, so that the MTA
      could be used to evaluate patients with PD in daily clinical practice. RESULTS:
      In normal subjects, MT progressively increased with aging, and was slower on the
      non-dominant side than on the dominant side. No differences were found between
      men or women. CONCLUSION: Our data provide further information about normative
      values on MT detected by MTA, and indicate that age and handedness are the main
      variables influencing motor task performance.

PMID- 16110734
TI  - Relationship between falls and physical performance measures among community
      dwelling elderly women in Japan.
AB  - BACKGROUND AND AIMS: The relationship between falls and physical performance has
      focused on the frail elderly who have several health problems, particularly those
      in nursing homes or care facilities. It is important to clarify the relationship
      between falls and physical performance among the community-dwelling elderly.
      METHODS: We examined the relationship between falls and physical performance
      measures (grip strength, chair stand time, functional reach, usual walking speed)
      among 402 community-dwelling Japanese elderly women aged 60 years and over.
      RESULTS: Overall prevalence of falls was 21.1%, and increased with age. In
      univariate analysis, grip strength and functional reach were not significantly
      different between women who did and did not fall. Chair stand time of women who
      fell was longer than that of women who did not (p = 0.05), and the usual walking
      speed of women who fell was significantly slower than that of women who did not
      fall (p < 0.0001). Physical functioning significantly decreased with age; grip
      strength, functional reach and usual walking speed decreased, and chair stand
      time increased. Logistic regression analysis, adjusting for age and other
      covariates, showed that slower usual walking speed was significantly associated
      with falls, but grip strength and functional reach were not. Increased chair
      stand time had a borderline association (p = 0.1). CONCLUSIONS: Our findings
      indicate that poor lower extremity function, especially walking ability, is an
      important risk factor for falls in elderly Japanese community-dwelling women.

PMID- 16110735
TI  - A fatigue resistance test for elderly persons based on grip strength: reliability
      and comparison with healthy young subjects.
AB  - BACKGROUND AND AIMS: Although a wide variety of protocols are available for
      evaluating skeletal muscle fatigue resistance, they often necessitate important
      technological resources or are too complicated for elderly subjects. We present
      here a new test, designed for elderly persons, based on maintaining maximal
      voluntary grip strength as long as possible. The aim of the study was to
      determine the reliability of this test procedure in hospitalized geriatric
      patients and in young healthy persons. METHODS: Fatigue resistance was considered
      as the time in which grip strength decreases to 50% of its maximum value. Twenty
      geriatric, hospitalized patients (age 83 +/- 6 yrs) and thirty-nine young,
      healthy persons (age 23 +/- 4 yrs) were evaluated for fatigue resistance by two
      different observers. Height, weight and body mass index were determined for each
      participant and the current amount of sports activity was recorded in the young
      subjects. RESULTS: All participants were able to perform the test. Inter- and
      intra-rater reliability in both subgroups was good to excellent, with ICC(3,1)
      values ranging from 0.77 to 0.94. No significant differences in inter- and intra
      rater measurements were found, except for inter-observer evaluations of the
      dominant hand in hospitalized geriatric patients. No significant relationships
      were found between fatigue resistance and maximal grip strength, anthropometrics
      or gender. CONCLUSIONS: The proposed fatigue resistance test is a reliable tool
      to evaluate geriatric hospitalized patients as well as young, active and healthy
      persons. Fatigue resistance scores are not related to gender, maximal strength or
      anthropometrics within the observed subgroups.

PMID- 16110736
TI  - Mental imagery. Effects on static balance and attentional demands of the elderly.
AB  - BACKGROUND AND AIMS: Several studies have demonstrated the effectiveness of
      mental imagery in improving motor performance. However, no research has studied
      the effectiveness of such a technique on static balance in the elderly. This
      study evaluated the efficiency of a mental imagery technique, aimed at improving
      static balance by reducing postural oscillations and attentional demands in the
      elderly. METHODS: Twenty subjects aged 65 to 90 years old, divided into two
      groups (8 in Control group and 12 in Experimental group) participated in the
      study. The experimental participants underwent daily mental imagery training for
      a period of six weeks. Antero-posterior and lateral oscillations, reaction times
      during the use of the double-task paradigm were measured, and the Berg Balance
      Scale, Activities-specific Balance Confidence Scale, and VMIQ questionnaire were
      answered during both pre-test and post-test. RESULTS: Attentional demands and
      postural oscillations (antero-posterior) decreased significantly in the group
      with mental imagery training compared with those of the Control group. Subjects
      in the mental imagery group became significantly better in their aptitudes to
      generate clear vivid mental images, as indicated by the VMIQ questionnaire,
      whereas no significant difference was observed for the Activities-specific
      Balance Confidence Scale or Berg Scale. CONCLUSION: The results support
      psychoneuromuscular and motor coding theories associated with mental imagery.

PMID- 16110737
TI  - Ten-year change in disability prevalence and related factors in two generations
      of French elderly community dwellers: data from the PAQUID study.
AB  - BACKGROUND AND AIMS: Some studies have reported a decline in disability
      prevalence in older people, but few data were available for Europe, especially
      for France. Our aim was to study the 10-year evolution of disability prevalence
      in elderly community dwellers and related factors. METHODS: Two generations of
      subjects aged 75 to 84, participants in the PAQUID (Personnes Agees QUID) cohort
      were compared. The first generation included 1496 subjects (born between 1903 and
      1912) and the second 910 subjects (born between 1913 and 1922). Three domains of
      disability were assessed: mobility, Activities of Daily Living (ADL) and
      Instrumental ADL (IADL). Logistic regressions were used to explain the effect of
      generation on disability, controlling for sociodemographic characteristics,
      impairment, life-style, medical care, and social support. RESULTS: The percentage
      of subjects fully independent increased from 13.5 to 23.3% (p < 0.001). A large
      decline in disability prevalence independent of the controlled factors was
      observed for mobility in both genders [Odds Ratio for the second generation
      (OR(G2)) = 0.48, 95% CI 0.38-0.60]. When adjusting for age and education, the
      risk of IADL disability was significantly lower in women in the second generation
      (ORG2 0.61, 95% CI 0.49-0.77), and the generation effect was strengthened when
      adjusting for the other covariates, but unchanged in men (ORG2 1.09, 95% CI 0.81
      1.48). There was no significant change for ADL. CONCLUSIONS: A significant
      decline in disability prevalence was observed over 10 years, which was not
      explained by the selected covariates. These aggregate changes differed by gender,
      education, and the domain of disability considered.

PMID- 16110738
TI  - Differences between participants and non-participants in an RCT on physical
      activity and psychological interventions for older persons.
AB  - BACKGROUND AND AIMS: Volunteer bias in intervention studies on successful aging
      has been poorly explored. This paper investigated differences between
      participants and non-participants of the Groningen Intervention Study on
      Successful Aging (GISSA) over a wide range of demographic, physical,
      psychological and social subject characteristics. METHODS: Subjects were
      recruited among a longitudinal cohort study (Groningen Longitudinal Aging Study)
      and included 558 men and 711 women, aged 65-96 years, who were invited to
      participate in the GISSA. Measures were obtained by questionnaires at the moment
      of invitation and eight years before invitation. Participants were compared with
      three groups of non-participants: persons who refused to participate, those who
      did not respond after a reminder, and those who intended to participate but
      withdrew before pre-test. RESULTS: At the moment of invitation, participants were
      younger, better educated, and functionally and physically more active than the
      three groups of non-participants. They also had better scores on the physical
      functioning subscale of the medical outcome scale, better ADL, iADL and vigorous
      ADL functions and fewer depressive symptoms, and perceived less social support in
      everyday and problem situations. Participants reported a less strong rate of
      decline in physical and psychological functioning in the eight years prior to the
      invitation than did the other groups. CONCLUSION: Due to volunteer bias, results
      of intervention studies on successful aging may have limited generalizability.

PMID- 16110739
TI  - Changes in the use of assistive devices among 90-year-old persons.
AB  - BACKGROUND AND AIMS: The growing numbers of elderly people are expected to lead
      to an increasing demand for assistive devices. The purpose of this study was to
      examine changes in the use of assistive devices over time and their relation to
      dependence in daily activities among 90-year-old persons living at home. METHODS:
      This retrospective longitudinal study examined the 90-year-old population at the
      ages of 85 and 90, and 195 persons participated. RESULTS: 92% of the 90-year-old
      population used assistive devices at the age of 90, compared with 74% at the age
      of 85. Between this interval, 19% became new users, 73% were permanent users, and
      7% did not make any use of assistive devices. There was a significantly higher
      proportion of device-users among those who were dependent in both personal daily
      activities (PADL) and instrumental activities of daily living (IADL) (98.5%, p <
      0.001) and among those who were dependent in IADL (94%, p < 0.001) compared with
      those who were independent in ADL (72%). At the age of 90, bathing and mobility
      devices were the most frequently used. Mobility devices such as walking-frames
      and wheel-chairs were the most widely distributed devices in this group.
      CONCLUSIONS: The use of assistive devices increases with age, very few 90-year
      olds remain nonusers at age 90, and the multiple use of assistive devices at 90
      years of age is very common. This complexity put great demands on health care
      services, and highly skilled professionals are needed to meet these demands.

PMID- 16110740
TI  - [Cadaveric topography and morphometry of the vermiform appendix].
AB  - Our study justified by the frequency of acute appendicitis and the possibility of
      anatomic variations of the caecoappendicular area attempt to index the
      topographic variations of the vermiform appendix (v.a.). On 80 fresh native
      cadavers (62 men and 18 women) without surgical antecedent whose mean age was 36
      years (range between 16 and 78 years) we note the morphotype and the height. More
      over we study the intraperitoneal projection of the Mac Burney point, topography
      and shape of the cecum and the situation, shape and dimensions of the v.a. We
      note also the level of implantation of this latter on the cecum, appearance of
      the mesoappendix and the distance separating the base of the appendix to the ileo
      caecal junction. Mac Burney's point permitted to localize appendix in 66%; the
      cecum has more often than not the form of a bulb (98.7%) and sited in right fossa
      iliaca. We noted 7 types of topographic disposition; front varieties were more
      frequent (68.7%) notably the pelvic direction (51.2%) with a medial (72.5%) or a
      posteromedial (27.5%) establishment on the cecum. The v.a. was more often in the
      form of worm with a long mesoappendix; his mean length was 106.4 mm (between 65
      and 160 mm) and the mean diameter 6.77 mm (range between 4 and 10 mm). The
      distance which separated the base of the appendix to the ileo-cecal junction
      varied between 15 to 40 mm with a mean distance of 24.2 mm. Thus in this study,
      dimensions of the v.a. were very variables. Located in right fossa iliaca he
      adopted a front topography with pelvic direction and medial establishment on
      bulbar cecum. In spite of scarcity of ectopic situation of the appendix for which
      laparoscopic approach is salutary, a similar topographic study during surgical
      treatment of acute appendicitis will be interesting.

PMID- 16110741
TI  - [Osseus age of the black children of Benin. A population study of 600 children
      aged from 9 to 18 years and living in Cotonou].
AB  - PURPOSE: The purpose of this work is to study the skeleton maturation in the
      black population of Benin by means of Tanner Whitehouse method (TW2) in
      comparison with the populations of the developed countries. MATERIAL AND METHODS:
      The study was transversal and analytic. It included 297 boys and 303 girls aged
      from 9 to 18 years. This was conducted from October 2002 to May 2003 in Cotonou
      City, the economic capital of Benin. The corrected minimum size of the sample was
      384 x 1.19. The sampling technique was chancy, multiphasic, stratified and in
      clusters. Every one of the 13 districts of Cotonou was considered as a stratum.
      The interpreter of the anteroposterior radiograph of the left wrist and hand was
      selected after an intra and extra observer test. The data treatment and analysis
      were performed by the logiciels Epi info and SPSS. The statistical tests used
      were Khi 2 test and Kappa index. RESULTS: The sample was mainly composed of
      pupils: 84.16% among the boys, 77.23% among the girls. 91.01% of the parents of
      the children had a middle standard of living. The skeleton maturation score
      increased with age in all TW2 methods. With the TW2 20 bone and RUS methods, the
      mature score was reached at percentile 50 among the boys at 18.5 years and among
      the girls at 17 years. It was precociously reached at percentile 97 respectively
      at 14 and 14.3 years among the boys and 12.7 years among the girls. With the
      Carpal bone method, the age of mature score at percentile 50 was 18.2years among
      the boys and 17.2 years among the girls. The early maturation was obtained at
      percentile 97 among the boys and the girls respectively at 13.2 and 12.5 years.
      DISCUSSION: The skeleton maturation score of the girls in Benin is I to 1.5 years
      higher than the one of the boys. With the TW2 bone and the RUS methods, the
      maturation shows a delay of 0.5 to 2.5 years at the percentile 50 and of 1.5 to 2
      years at the percentile 97 in relation to the Belgian, British, Chinese, Korean,
      Japanese, and North American standards. These delays seem to be mainly due to the
      less favourable socioeconomic conditions in Benin. In the other hand, the more
      considerable delay of 1 to 4 years with the Carpal bone method remains to be
      elucidated. CONCLUSION: The osseous age stemming from this work is representative
      of the middle social stratums of the city backgrounds. It would gain to be
      completed by a similar work concerning the country backgrounds of Benin.

PMID- 16110742
TI  - An unusual familial chromosome 9 "variant" with variable phenotype:
      characterization by CGH analysis.
AB  - Heterochromatin confined to pericentromeric and secondary constriction regions
      plays a major role in morphological variation of chromosome 9, because of its
      size and affinity for pericentric inversion. We report on a 6-year-old boy with
      growth and language delay, minor facial anomalies and unusual chromosome 9
      variant with an extra-band in the centromeric region on the conventional
      karyotype. Subsequent analysis by FISH and CGH identified this variant as a
      dicentric chromosome 9 with a duplication of the 9p12-q21 region. An identical
      chromosome 9 variant was found in the mild language retarded brother and in the
      phenotypically normal father and grandfather. The presumed mechanism accounting
      for the phenotypic discordance observed in this family and the usefulness of CGH
      in characterization of such variants are discussed. To our knowledge, this is the
      first investigation of an unusual chromosome 9 variant by CGH.

PMID- 16110743
TI  - [Portal vein: variations of its branches (about 32 dissections)].
AB  - PURPOSE: The aim of this study is to precise the variations of portal vein
      branches and also to elucidate anatomic basis of partial hepatectomy. MATERIAL
      AND METHODS: Thirty-two post-mortem specimens, with ages ranged from one day to
      sixty-five years in both two sexes, were dissected. Latex and Rhodopas were used
      for visualizing and drawing the portal vein course and its branches. RESULTS:
      Nine types of different variations of portal vein branches were observed. Most of
      cases were similar to those previously reported in literature. But four types
      must be especially noted, because they were not available in literature.
      DISCUSSION: this study updates the anatomy of portal vein and its tributaries,
      and also finds out four types of distribution which must be known by surgeons
      with regards to partial hepatectomy.

PMID- 16110744
TI  - [Expression of caspase 3 and p53 during physiological apoptosis and apoptosis
      induced by three teratologic agents during early craniofacial development of the
      mouse embryo].
AB  - The neural crest-derived mesectoderm gives rise to physiologic apoptosis areas in
      early vertebrate embryos. Certain teratologic agents increase this phenomenon.
      The purpose of this work was to detect caspase 3 (which is associated with the
      apoptosis cascade) and p53 in cell death areas, both during physiological
      apoptosis and during apoptosis induced by three agents (retinoic acid, methyl
      triazene, irradiation). Antibody revelation was performed using the aBC
      peroxidase kit. Quantifications were also performed on histological sections. We
      observed caspase 3 uptake on some apoptotic and preapoptotic cells in control
      embryos, and in the embryos exposed to the three teratogens. Immunoreactivity
      generally preceded the development of cytological features of apoptosis. However,
      p53 was expressed only in the embryos exposed to ionizing radiation and methyl
      triazene (an alkylating agent), but not significantly in embryos exposed to
      retinoic acid. The present results throw some light on apoptosis mechanisms in
      several teratologic conditions.

PMID- 16110745
TI  - [The choroid plexuses: a dynamic interface between the blood and the
      cerebrospinal fluid].
AB  - The choroid plexuses form one of the interfaces that control the brain
      microenvironment by regulating the exchanges between the blood and the central
      nervous system. They appear early during brain development. Originating from four
      different areas of the neural tube, they protrude into the ventricular system of
      the brain. The choroidal mechanisms involved in the control of brain homeostasis
      include the structural properties of the epithelial cells that restrict
      diffusional processes, as well as specific exchange and secretion mechanisms. In
      addition to the anatomical and histological organization of the choroidal tissue,
      this review describes the mechanism of cerebrospinal fluid secretion which is the
      most studied function of the choroid plexus. Experimental evidence for an
      implication of the choroid plexuses in neuroprotective mechanisms and in the
      supply of biologically active polypeptides to the brain are also reviewed.

PMID- 16110746
TI  - [Hands and feet of Simian primates: an attempt at morphological
      characterization].
AB  - The carpal height, the length of the metacarpus, the metatarsus, and of all the
      phalanges of 269 simians were measured, then for each specimen, converted to
      percentage taking the 3rd metacarpus as the reference unit. They were then
      compared despite differences between specimens. The average values were
      determined for the different species, subspecies or families. Mathematical ratios
      were established: height of the carpus divided by the 3rd metacarpus, carpus
      divided by the 1st metacarpus, 1st ray of the hand divided by the 2nd, 1st ray of
      the hand divided by the 1st ray of the foot. CONCERNING THE HAND: For little
      monkeys, the length of the carpus and the medial metacarpus were similar to those
      observed in humans. Colobinae exhibited a relatively short thumb column. The
      length of the thumb was slightly shorter for the platyrrhinii and
      cercopithecinae, especially macacus. Some hapalidae had a relatively longer thumb
      than humans. All of their medial fingers were longer than those observed in
      humans. The big monkeys had a smaller carpus and thumb column, sometimes much
      smaller than in humans, with a similar length for the metacarpi and the medial
      fingers, except for gibbons, whose medial fingers were longer. CONCERNING THE
      FOOT: The 1st ray in humans is nearly as long as the 2nd toe, the other toes
      being very short. The 1st ray of the hallux of all monkeys was always longer than
      the ray of the thumb, but shorter than the hallux of humans. The other metatarsi
      of little monkeys were similar to those in humans, except for the platyrrhinii
      which had a shorter 2nd metatarsus. The lateral toes, which were much longer than
      in humans, were very similar to fingers though slightly longer, except for
      platyrrhinii with much longer toes. The big monkeys had very short metatarsi and
      slightly smaller lateral toes than humans.

PMID- 16110747
TI  - Stem cells and frontiers of therapeutic advances in cancer.
AB  - Cancer is a dreadful disease characterized by unscheduled and uncontrolled
      abnormal cell proliferation. The cause(s) of cancer incidence are varied and
      involve multiple etiological factors. Recent studies provided ample evidences
      that apart from the chemo- and radio-therapeutic approaches, the immunological
      defense can be manipulated as an effective therapeutic module by directing immuno
      competent cells against the cancer target. This ultimately constituted the anti
      cancer cytotherapy or cell therapy, which included the natural killer (NK) cells,
      specifically directed cytotoxic cells, dendritic cells and other immune-killer
      cells. Stem cells, above all, occupied the most important position by
      contributing to the constituent cellular potential on one hand, and, secondly,
      acting as a docile vehicle for targeted gene therapy. Worldwide, attempts are now
      being made to achieve successful therapeutic approaches with stem cells against
      both haematological malignancies as well as various solid tumors. The adult stem
      cell corpuscular therapy has been reported to be the most inspiring and safe
      module for cancer therapy.

PMID- 16110748
TI  - Prostate cancer: the role of hormonal therapy.
AB  - Prostate cancer is the cause of more than 1% of all deaths in men. Its incidence
      is increasing by 2-3% per year. The general prognosis for diagnosed prostate
      cancer remains poor, with 70% survival at 10 years compared to the general
      population. About 50% of the cases are diagnosed at a locally advanced stage, and
      about 30% have bone metastases at the time of diagnosis. Adjuvant systemic
      treatments (hormones or chemotherapy), which are effective for advanced-stage
      disease, might have a greater role in early-stage disease. Advanced prostate
      cancer is an incurable disease. Treatment objective is palliation only. Here, we
      review the major controversies concerning hormonal therapy, and provide a general
      approach to management of patients with early-stage and advanced prostate cancer.

PMID- 16110749
TI  - Sentinel node identification by scintigraphic methods in cutaneous melanoma.
AB  - In melanoma patients lymph node metastasis is an important prognostic factor that
      indicates the need for therapeutic lymph node dissection. Preoperative
      lymphoscintigraphy mapping associated with radioguided sentinel lymph node biopsy
      has become a well established procedure for cutaneous melanoma patients without
      clinically detectable lymph node metastases (stage I, II). This technique is a
      versatile way of characterizing the lymphatic basin at risk for metastases and
      identifying involved lymph nodes. The purpose of the present study was to examine
      the reproducibility of lymphoscintigraphy and sentinel lymph node biopsy in
      detecting micro metastases in cutaneous melanoma. The study was a single
      institution prospective analysis of 74 melanoma patients, with primary tumors
      having Breslow thickness > 0.7 mm, who underwent lymphoscintigraphies between May
      2002 and September 2003. Technetium-99m sulfur colloid was injected intradermally
      at the primary tumor site and dynamic images were obtained for 40 minutes. Two
      observers evaluated the images. One to two weeks after the first
      lymphoscintigraphy, radioguided lymph node biopsy was performed. For the biopsy,
      technetium-99m sulfer colloid was injected intradermally in the same manner as
      performed before. Lymph nodes were identified and removed with the aid of a gamma
      ray detecting probe (GDP), and were submitted to histopathological analysis. The
      histopathological analysis of the sentinel lymph nodes collected during surgery
      was performed in a sequential manner. First, frozen sections were analyzed during
      surgery. The lymph nodes considered negative by frozen section were analyzed by
      H&E staining. Subsequently, the slides considered negative with H&E were sent for
      immunohistochemical analysis. Lymphoscintigraphy identified at least one sentinel
      lymph node in all patients. Sentinel node biopsy detected metastases in 20
      patients (27.2%). In all cases the lymph node basins identified during
      lymphoscintigraphy were found to have at least one sentinel lymph node during
      surgery. Frozen section analysis of the lymph node was only able to identify the
      disease in 35% of the patients eventually found to have micrometastases with H&E
      and immunohistochemistry. Two lymph nodes were negative with H&E and positive
      with immunohistochemical analysis. In conclusion, lymphoscintigraphy is a simple
      procedure that is well tolerated by patients. It is useful in locating sentinel
      lymph nodes in patients with melanoma and is an important tool in the clinical
      practice of oncology. We recommend performing H&E, and if necessary,
      immunohistochemical analysis of all sentinel lymph nodes because of the high rate
      of false negative results with frozen sections alone.

PMID- 16110750
TI  - Activity and toxicity of oxaliplatin and bolus fluorouracil plus leucovorin in
      pretreated colorectal cancer patients: a phase II study.
AB  - The aim of the current study was to evaluate the activity and toxicity of a
      combination of oxaliplatin with bolus fluorouracil and leucovorin in colorectal
      cancer (CRC) patients pretreated for advanced disease with various schedules
      including continuous fluorouracil infusion. Thirty consecutive patients with
      pretreated advanced CRC received oxaliplatin 130 mg/m2 by 2-h infusion dl,
      leucovorin 100 mg/m2 by 1-h infusion followed by fluorouracil 425 mg/m2 i.v.
      bolus from day 1 to 3 every 3 weeks for a maximum of 6 cycles. The best overall
      response rate in an intent-to-treat analysis was 13% (2 complete responses and 2
      partial responses) (95% CI, 1.2-25.5%) and 37% of patients obtained stable
      disease with a tumor growth control rate of 50% (95% CI, 32.1-67.9%). The median
      progression-free survival was 4.0 months (95% CI, 1.4-6.5 months) and median
      overall survival was 12.0 months (95% CI, 9.9-14.1 months). The independent
      prognostic factors for improved overall survival were a good performance status
      and a response/stabilization of disease to chemotherapy. Severe neutropenia was
      quite common (43.3% of patients and 14.4% of cycles), although complicated by
      fever only in one case (3.3% of patients). There was one toxic death. In
      conclusion, the study combination showed an interesting rate of tumor growth
      control in a cohort of patients previously treated for advanced disease with
      various schedules including continuous fluorouracil infusion.

PMID- 16110751
TI  - Epoetin alfa 40000 U once weekly and intravenous iron supply in solid tumor
      patients: early increase of hemoglobin level during chemotherapy.
AB  - The objective of this observational study was the early evaluation of the impact,
      a week after the first administration of epoetin alfa 40000 U once weekly and
      i.v. dose of 62.5 mg sodium ferric gluconate for seven days in improving
      hemoglobin levels in cancer patients affected by mild/moderate or severe anemia
      during chemotherapy. Twenty patients affected by solid tumors who received
      epoetin alfa 40000 U once weekly and daily i.v. sodium ferric gluconate for one
      week were evaluated: 90% of the patients showed hemoglobin increase, with a
      median level of hemoglobin increase of 0.73 g/L from baseline, and 50% of them
      showing a hemoglobin increase > 1 gr/L. The treatment was well tolerated and no
      adverse event was observed. The early increase of hemoglobin level from baseline
      is interesting and suggestive for the possibility of achieving an adequate
      hemoglobin level with a short-term treatment. It is still necessary to further
      explore the real need of iron supplementation to maintain adequate erythropoiesis
      prior and during epoetin therapy.

PMID- 16110752
TI  - Brain metastasis from prostate cancer. Report of 13 cases and critical analysis
      of the literature.
AB  - Brain metastasis from prostate carcinoma occurs very rarely. We describe 13
      patients with single brain metastasis from prostatic cancer. Total removal of the
      lesions was performed in ten patients. Three patients underwent stereotactic
      biopsy. All patients were treated with postoperative whole brain radiotherapy
      (WBRT). Eight patients died for systemic disease after a mean time of 9.2 months
      with a diagnosis of metastasis. Five patients are still alive at 20, 14, 11, 7
      and 6 months, respectively. Even if brain metastasis from prostate cancer is
      often a terminal event with death occurring within few months from diagnosis, we
      suggest the same protocol (surgery and/or radiosurgery plus postoperative WBRT)
      usually adopted to treat brain metastasis from other primitive tumours. A non
      specific neurological symptomatology and a possible normal dosage of serum
      specific antigen may contribute to a delay in diagnosis. However, considering the
      rarity of brain metastasis from prostate carcinoma, standard brain MRI follow-up
      in men with prostatic cancer does not seem to be necessary yet.

PMID- 16110754
TI  - The use of chromosome aberrations in predicting breast cancer risk.
AB  - In order to assess the usefulness of chromosome aberrations in predicting breast
      cancer risk, 10 patients with breast cancer diagnosis and appropriately matching
      10 healthy controls were chosen. Spontaneous and radiation induced unstable
      chromosome aberrations in peripheral blood lymphocytes were compared in the two
      groups. When the spontaneous aberration frequencies were compared, acentric
      chromosome frequency, scored in the group of patients was significantly higher
      than that found in the control group (p<0.01). Absolute aberration frequencies as
      a determinant of radiosensitivity were calculated by subtracting spontaneous
      aberration frequencies from the frequencies that were obtained following 2 Gy of
      Co-60 gamma irradiation. Absolute dicentric chromosome frequency significantly
      increased in the patients1 group (p<0.01) as compared to that observed in the
      control group. Increases in either spontaneous acentric chromosome frequency or
      dicentric chromosome frequency as a determinant of an enhanced radiosensitivity
      in the group of patients may be valuable in predicting breast cancer risk. The
      studies involving unstable chromosome aberrations can be easily performed and can
      facilitate cancer diagnosis with minor effort and low cost.

PMID- 16110753
TI  - Characterization of tumoral lesions of the breast: preliminary experience with
      multislice spiral CT.
AB  - The aim of the present study was to validate low dose Multislice Spiral Computed
      Tomography (MSCT) in the diagnosis of breast lesions. Fourteen patients with
      mammographic and ultrasound findings suspect of malignant neoplasm underwent
      dynamic MSCT of the breast under basal conditions and 1, 3, and 6 minutes after
      intravenous injection of iodinated contrast medium. Both enhancement of the
      lesion >100% without further increase after 6 minutes, and irregular margins of
      the lesion were considered signs of malignancy. All lesions were examined
      cytologically and/or histologically. A correct diagnosis was achieved by MSCT in
      7/8 malignant lesions, and in 6/6 benign lesions. The only malignant lesion
      missed by MSCT was histologically a ductal carcinoma in situ (false negative). In
      one case the MSCT showed the multifocality of an infiltrating ductal carcinoma,
      and in another it defined the bilaterality of the malignant lesions. Sensitivity
      and specificity of MSCT in the diagnosis of malignancy of a lesion were 88% and
      100%, respectively. Our results suggest that MSCT is an effective diagnostic
      method to define suspicious breast lesions, and a valid alternative to Magnetic
      Resonance Imaging, especially when the latter is not feasible.

PMID- 16110755
TI  - Modulation of xenobiotic-metabolizing enzymes by ethanolic neem leaf extract
      during hamster buccal pouch carcinogenesis.
AB  - Chemoprevention by medicinal plants is a promising approach for controlling
      cancer. There is substantial evidence to indicate that chemopreventive agents
      exert their anticarcinogenic effects by modulation of phase I and phase II
      xenobiotic-metabolizing enzymes. Therefore, we examined the chemopreventive
      potential of ethanolic neem leaf extract (ENLE) on 7,12-dimethylbenz[a]anthracene
      (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided
      into four groups of six animals each. The right buccal pouches of animals in
      Group I were painted with 0.5 per cent DMBA in liquid paraffin three times per
      week. Animals in Group 2 painted with DMBA as in group 1, received in addition,
      intragastric administration of ENLE at a concentration of 200 mg/kg bw three
      times per week on days alternate to DMBA application. Group 3 was given ENLE
      alone. Animals in Group 4 served as controls. All animals were killed after an
      experimental period of 14 weeks. Five out of six hamsters painted with DMBA alone
      developed squamous cell carcinomas in the buccal pouch. The HBP tumours showed an
      increase in phase I carcinogen activation (cytochrome P450 and b5) and phase II
      detoxification enzyme (glutathione-S-transferase, DT-diaphorase and NADPH
      diaphorase) activities. In the liver of tumour-bearing animals, enhanced
      cytochrome P450 and b5 levels were accompanied by a decrease in phase II
      detoxification enzyme activities. Administration of ENLE effectively suppressed
      DMBA-induced HBP tumours, decreased cytochrome P450 and b5 levels, and enhanced
      phase II enzyme activities in the pouch and liver. Our results suggest that the
      modulation of DMBA metabolism is a possible mechanism for the chemopreventive
      effects of ethanolic neem leaf extract.

PMID- 16110756
TI  - High risk for microcarcinoma in thyroid benign diseases. Incidence in a one year
      period of total thyroidectomies.
AB  - Over the last few years, incidental thyroid microcarcinoma (TMC) has become a
      frequent disease and its incidence in some reports is considerable. The discovery
      of new cases depends on the progress of the diagnostics (US scan, fine needle
      biopsy and cytology, CT, MRI), on the extended indications to thyroidectomy for
      benign disease and on the attention in pathologic examination of the specimen.
      The clinical evolution of this disease is not well known: in spite of a high
      incidence reported in some autoptic series, suggesting that this tumour could
      have a good prognosis, some authors report an overall incidence of up to 11% of
      local recurrence, metastasis and mortality. For these reasons the treatment of
      TMC is still controversial today. Aim of this study was to estimate the incidence
      and the clinico-pathological findings of TMC over a one year period of total
      thyroidectomies for diffuse benign thyroid diseases, and to evaluate, on the
      basis of the frequency of incidental microcarcinoma, if the surgical procedure of
      complete removal of the gland should be adopted in any case. In this series no
      patient had pre-operative diagnosis or tentative diagnosis of carcinoma and the
      incidence of TMC at the final histologic examination was 27.4%. Total
      thyroidectomy confirmed to be the treatment of choice for diffuse benign diseases
      and appeared necessary to obtain both, diagnosis and treatment of incidental TMC.

PMID- 16110757
TI  - Antibody against vascular endothelial growth factor (VEGF) inhibits angiogenic
      switch and liver metastasis in orthotopic xenograft model with site-dependent
      expression of VEGF.
AB  - We previously reported that upregulation of angiogenesis, i.e. angiogenic switch
      (AS), may occur simultaneously to initiation of invasion in the early development
      of human colon cancer. We also showed that mRNA upregulation of the gene of
      vascular endothelial growth factor (VEGF) occurs immediately prior to metastasis
      in human colon cancer in an orthotopic nude mouse model of colon cancer liver
      metastasis. In this paper, we studied whether the antibody against VEGF inhibits
      AS and liver metastasis in an orthotopic xenograft model with site-dependent
      expression of VEGF. We examined levels of vessel density, VEGF mRNA by in situ
      hybridization (ISH) method and liver metastasis in pre-AS (on days 8 and 11) and
      post-AS (on days 15 and 18) treatment groups. The mean vessel density and the
      intensity of VEGF mRNA by ISH in the pre-AS treatment group were significantly
      lower than those for the post-AS treatment and the control group. Liver
      metastases were completely inhibited (0/10) in the pre-AS treatment, while they
      occurred in 4 out of 10 and 5 out of 10 mice in the post-AS treatment and the
      control groups, respectively (p<0.01). These results suggest that VEGF antibody
      treatment performed before AS could efficiently inhibit AS and liver metastasis,
      which may indicate that VEGF antibody has another potential as a drug for
      chemoprevention of colon cancer.

PMID- 16110758
TI  - Rational design of new electrodes for electrochemotherapy.
AB  - Electrochemotherapy associates the local delivery of anticancer drugs with the
      administration of permeabilizing electric pulses that support the antiblastic
      action. The basic instrumentation for this therapy is constituted by a pulse
      generator and various specific electrodes. While many efforts have been profuse
      by researchers in this field to obtain the standardization of the pulse
      generating equipment over the past 15 years, the delivery apparatus still needs
      refinements in order to reach most of the body districts, to control the
      homogeneity and stability of the electric fields and to further reduce morbidity.
      With the aim to develop innovative electrodes able to satisfy, at least
      partially, these requirements, extensive studies on pet patients with spontaneous
      neoplasms have been conducted, leading to the manufacturing of several different
      prototypes. In this paper we discuss the rationale of 11 different electrodes,
      briefly summarize the results obtained and their experimental validation, also
      presenting five paradigmatic clinical cases. In particular, it is shown that the
      caliper electrodes are more suited for the treatment of cutaneous and
      subcutaneous lesions, while the needle arrays are more efficacious in
      intraoperative settings. Furthermore, relevant peculiarities of unipolar
      electrodes are examined with a particular focus on the irregular current paths
      that they produce and on the potentialities of this feature. Remarkably, the
      decrease of the steric encumbrance turned out to be a stronger factor in
      electrode design than the containment of the total number of electric fields
      covered in serial ECT sessions. In the conclusions, perspectives and new
      challenges of electrode design for electrochemotherapy are illustrated.

PMID- 16110759
TI  - Effect of morphine on cell-mediated immune responses of human lymphocytes against
      allogeneic malignant cells.
AB  - Opioid drugs, including morphine, are largely used as pain control in cancer
      patients at different stages of neoplastic growth and progression. Therefore, the
      possible influence of these drugs on host immunity appears to be of considerable
      interest. We have examined in vitro the effect of morphine on the generation of
      human cytotoxic T lymphocytes (CTL) against HTLV-I induced T-cell leukemia cells
      (MT-2 line). The results show that the drug, at graded concentrations (from 3
      pg/ml to 32 microg/ml), that include those detectable in treated patients,
      enhances CTL activity whereas natural killer cell activity was unaffected. The
      enhancing effect is particularly evident when morphine was present at the onset
      of lymphocyte/MT-2 co-culture. On the contrary, the drug was ineffective when
      added on the last day of co-culture, thus indicating that morphine operates
      during the generation phase of CTL, but not on mature CTL. Flow cytometric
      analysis of intracellular cytokine expression showed that morphine increases the
      percentage of interferon gamma-producing CD8+ T cells in co-culture assay.
      Collectively, these results suggest that in our experimental model morphine
      enhances CTL responses by directly affecting the induction phase of T-dependent
      cell-mediated immunity.

PMID- 16110760
TI  - Human mammaglobin mRNA is a reliable molecular marker for detecting occult breast
      cancer cells in peripheral blood.
AB  - Occult carcinoma cells in peripheral blood of breast cancer (BC) patients is
      generally associated with poor disease prognosis. Reverse transcriptase
      polymerase chain reaction (RT-PCR) is a sensitive method for revealing rare
      circulating cancer cells. The target mRNA must be carefully chosen, as it must be
      expressed only by malignant cells. In this study, we developed a nested RT-PCR
      assay for mammaglobin (hMAM) and assessed both its specificity and its
      sensitivity in the detection of cancer cells in peripheral blood of BC patients.
      hMAM mRNA was detected by RT-PCR in 156/165 (95%) of fresh BC tissues analyzed.
      All samples from 66 healthy blood donors and 151 patients with benign breast
      disease were hMAM negative as assessed by nested RT-PCR. In contrast, hMAM was
      detected in 16/137 (12%) of peripheral blood samples deriving from BC patients:
      0/9 in stage 0, 1/50 (2%) in stage I, 3/33 (9%) in stage II, 1/18 (5%) in stage
      III and 11/27 (41%) in stage IV. Using nested RT-PCR, we were able to amplify
      hMAM transcript of one tumour cell/10(6) normal cells. Our data demonstrate that
      hMAM mRNA detection by RT-PCR is a specific assay potentially suitable for
      identification of occult cancer cells in peripheral blood of BC patients.

PMID- 16110761
TI  - Prognostic value of DNA analysis of prostate adenocarcinoma: correlation to
      clinicopathologic predictors.
AB  - The ability to accurately predict tumor behavior and patient survival is a
      problem in managing patients with prostate cancer. DNA ploidy provides important
      information for the evaluation of the prognosis of prostate cancer. The aim of
      this study was to investigate the DNA ploidy in imprints from prostate
      adenocarcinomas in a group of 70 patients in relation to Gleason score, tumor
      differentiation, stage and PSA serum levels. The DNA content was studied in
      Feulgen-stained imprint smears through the image analysis technique using a SAMBA
      2005 Image analyzer. According to our measurements, a strong correlation was
      observed between DNA ploidy status and tumor differentiation (p<0.001). A
      statistically significant difference was found between DNA aneuploidy and
      increased pretreatment PSA serum levels (>4 ng/ml) (p<0.001), as well as between
      ploidy pattern and stage of the disease (p<0.001). Our results conclude that DNA
      ploidy status appears to be an additional marker in the field of prognosis of
      prostatic adenocarcinoma and could provide useful information on the potential
      behavior of prostate cancer.

PMID- 16110762
TI  - Differential stromal and epithelial localization of cyclooxygenase-2 (COX-2)
      during colorectal tumorigenesis.
AB  - The purpose of the following study is to describe the localization of COX-2
      protein and COX-2 mRNA during human colorectal tumorigenesis and to identify
      potential cellular targets for COX-2 inhibition in chemopreventive strategies.
      Immunohistochemistry with digital image analysis was used to determine COX-2
      protein expression in histologic sections containing synchronous normal
      colorectal mucosa, adenomas and carcinomas, from 17 previously untreated
      patients. Epithelial and stromal COX-2 mRNA expression was analyzed by reverse
      transcription-polymerase chain reaction (RT-PCR), on laser-capture microdissected
      samples from the same histologies. The stromal compartment in normal colorectal
      mucosa and adenomas showed higher levels of COX-2 protein expression compared to
      colorectal carcinomas (p < .0001). Conversely, epithelial COX-2 protein was
      significantly increased only after development of the invasive phenotype (p <
      .0001). RT-PCR demonstrated higher stromal COX-2 mRNA expression compared to that
      within the epithelium for colorectal adenomas and carcinomas. In conclusion,
      stromal COX-2 may be the target for chemopreventive agents in the early stages of
      colorectal carcinogenesis.

PMID- 16110763
TI  - Enhanced recognition of hydroxyl radical modified plasmid DNA by circulating
      cancer antibodies.
AB  - Reactive oxygen species have been implicated in various human diseases which are
      also responsible for the elimination of invading pathogens. In disease state and
      inflammatory responses, the excess of these radicals damage cellular
      macromolecules. DNA is susceptible to attacks by OH-induced damage. Oxidative DNA
      damage is an important factor in mutagenesis and carcinogenesis. In the present
      study, purified plasmid Bluescript DNA was modified by hydroxyl radical.
      Modifications incurred in DNA were characterized by physico-chemical techniques.
      Sera from patients of cancer were studied for their binding to native and
      hydroxyl radical modified plasmid DNA. Direct binding ELISA and competition
      binding results indicated that autoantibodies in cancer showed higher recognition
      to ROS-plasmid DNA as compared to the native form. Retarded mobility of the
      immune complex formation between IgG isolated from cancer sera using native and
      ROS-plasmid DNA as antigens reiterated preferential recognition of modified
      plasmid DNA by cancer autoantibodies. Therefore, it can be concluded that
      circulating autoantibodies in cancer sera bind preferentially to ROS-plasmid DNA
      as compared to native polymer. The data presented in the present communication
      suggest a role of ROS in the etiology of cancer.

PMID- 16110764
TI  - Effect of Smoke Shield-a herbal formulation on the mutagenicity and oxidative
      stress produced by cigarette smoke in rats.
AB  - Herbal formulation Smoke Shield was studied for its activity against cigarette
      smoke induced oxidative stress in rats. Smoke Shield administration was found to
      decrease the increased lipid peroxidation and conjugated dienes in the lung
      tissue and serum of cigarette smoke exposed rats. Moreover, administration of
      Smoke Shield was found to increase the activity of catalase in erythrocytes and
      lung tissue of rats, which was decreased upon smoke exposure. Glutathione
      peroxidase, which was increased by smoke exposure, was decreased by Smoke Shield
      and concomitantly there were increased levels of glutathione in the cells. In
      vitro studies indicated that addition of Smoke Shield could reduce the
      mutagenicity produced by tobacco smoke condensate, mosquito coil smoke condensate
      as well as by aqueous tobacco extract. In vitro antioxidant potential of smoke
      shield was found to be comparable or better than known antioxidants such as
      vitamin C and vitamin E. These results indicated that Smoke Shield administration
      could effectively reduce the oxidative stress produced in rats by cigarette smoke
      and it could inhibit mutagenicity produced by smoke condensates and tobacco
      extract in Salmonella typhimurium.

PMID- 16110765
TI  - Tumor induction by azoxymethane (AOM) and 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP) in F344 rat gastric mucosa featuring intestinal metaplasia
      caused by X-irradiation.
AB  - Male F344 5-week-old rats were X-irradiated, and 16 weeks after the first dose,
      azoxymethane (AOM) was injected or 2-amino-1 -methyl-6-phenylimidazo [4,5
      b]pyridine (PhIP) was given by intragastric intubation. Tumors in the pylorus of
      the glandular stomach were observed in 4 out of the 29 animals receiving X-rays +
      AOM and in 4 out of the 25 animals receiving X-rays + PhIP, 12 months after
      administration. No such lesions were found in the chemical or X-ray alone groups.
      Intestinal metaplasia and some induced tumors were positive for CDX2. It was
      concluded that the presence of intestinal metaplasia may increase sensitivity to
      the induction of gastric tumors by colon carcinogens.

PMID- 16110766
TI  - Locally advanced ovarian carcinoid.
AB  - Primary carcinoid tumor of the ovary is an extremely rare neoplasm, accounting
      for less than 0.1 % of all ovarian neoplasms. We report a case of a 79-year-old
      woman with locally advanced ovarian carcinoid presenting as acute abdomen. At
      laparotomy, a large mass appeared in the pelvis, with maximum size of 18 cm,
      growing from the left ovary with infiltration of the left Fallopian tube and
      compression of the small bowel and the sigmoid tract. A bilateral salpingo
      oophorectomy was performed, and the tumor mass was completely removed. Post
      operative treatments were not considered due to the absence of data in literature
      to support adjuvant treatments. Ten years after surgery the patient remains well
      without evidence of recurrence. Older age should not be considered an absolute
      contraindication for aggressive surgery, if this represents the best chance of
      cure. An aggressive cytoreductive surgery remains the best treatment for advanced
      or locally advanced primary ovarian carcinoid.

PMID- 16110767
TI  - Central nervous system mesenchymal chondrosarcoma.
AB  - Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that
      constitute a separate entity from the classical chondrosarcoma and myxoid
      variant. Clinical behaviour of central nervous system chondrosarcomas is still
      unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma
      with a review of the literature, in an attempt to clarify the clinical
      characteristics, prognosis and treatment of choice of these unusual tumors. Among
      the 55 reported cases, 23 had postoperative radiotherapy. Although there is no
      statistical significance according to the Log-Rank test (p=0.7), the patients
      treated with radiation therapy seem to have a better chance of survival. Patients
      who had adjuvant chemotherapy (only 5) showed survival times similar to those
      patients who had none. Although clinical behaviour of central nervous system
      chondrosarcomas remains to be defined, data from our series as well as literature
      show that radical removal is the best therapeutic choice. In addition, patients
      treated with postoperative radiotherapy seem to show a trend toward increased
      survival.

PMID- 16110768
TI  - Primary adenocarcinoma of cervical esophagus.
AB  - Most upper esophageal malignancies are squamous cell carcinomas, rarely
      adenocarcinomas arising from Barrett's esophagus and very rarely adenocarcinomas
      from heterotopic gastric mucosa without evidence of Barrett's especially in the
      cervical part of the esophagus. We report a case of adenocarcinoma of the
      polypoid type in the upper esophagus (cervical esophagus) arising from ectopic
      gastric mucosa, in a 60 year-old man who presented with progressive dysphagia.
      Accurate diagnosis by esophagogram revealed a large mass in the cervical
      esophagus; CAT scan showed intraluminal mass at the level of thoracic inlet,
      esophagogastroscopy showed a fleshy polyp (3.2cm x 3.0cm) at 20 cm from the
      incisors with a biopsy confirming moderately differentiated adenocarcinoma with
      no evidence of Barrett's esophagus. Through a left cervical approach and
      resection of medial third of clavicle, the tumor was removed by partial
      esophagectomy followed by lymph node dissection, and proved to be T1NOMO, stage I
      (AJCC staging 6th ed.). Post operatively, the patient received chemoradiation
      with no evidence of recurrence or metastasis in six years of follow up. It seems
      this tumor has a much better prognosis than adenocarcinomas arising from
      Barrett's. To our knowledge only 19 cases have been reported in literature so
      far.

PMID- 16110769
TI  - Side effects of transcranial magnetic stimulation biased task performance in a
      cognitive neuroscience study.
AB  - Transcranial magnetic stimulation (TMS) is increasingly used as a research tool
      for functional brain mapping in cognitive neuroscience. Despite being mostly
      tolerable, side effects of TMS could influence task performance in behavioural
      TMS studies. In order to test this issue, healthy subjects assessed the
      discomfort caused by the stimulation during a verbal working memory task. We
      investigated the relation between subjective disturbance and task performance.
      Subjects were stimulated during the delay period of a delayed-match-to-sample
      task above cortical areas that had been identified before to be involved in
      working memory. Task performance and subjective disturbance due to side effects
      were monitored. The subjects' grade of discomfort correlated with the error
      rates: the higher the discomfort, the more errors were made. Conclusively, TMS
      side effects may bias task performance in cognitive neuroscience studies and may
      thereby lead to misinterpretation of results. We emphasize the importance of
      controlling side effects of the stimulation as a source of biasing effects in TMS
      studies.

PMID- 16110770
TI  - Source localisation in a real human head.
AB  - Neural activity within the human brain produces electrical potentials that are
      transmitted through the various tissues of the head to the scalp. A three
      dimensional finite difference model has been applied to simulate this process and
      used as the basis for an inverse model, wherein known potentials on the scalp are
      used to locate sources of neural activity within the brain. The inverse model
      uses linear and nonlinear response functions, together with nonlinear regression
      to determine the source location. The model has been applied to three different
      simulations, and in each case was able to locate the source using a combination
      of linear and nonlinear response functions.

PMID- 16110771
TI  - The influence of Mozart's sonata K. 448 on brain activity during the performance
      of spatial rotation and numerical tasks.
AB  - The study investigated the influence of Mozart's music on respondents' brain
      activity while solving spatial rotation and numerical tasks. The method of
      induced event-related desynchronization/synchronization (ERD/ERS) and coherence
      (ERCoh) was used. The music condition had a beneficial influence on respondents'
      performance of spatial rotation tasks, and a slightly negative influence on the
      performance of numerical tasks as compared with the silence condition. On the
      psychophysiological level a general effect of Mozart's music on brain activity in
      the induced gamma band was observed, accompanied by a more specific effect in
      theinduced lower-2 alpha band whichwas only present while respondents solved the
      numerical tasks. It is suggested that listening to Mozart's music increases the
      activity of specific brain areas and in that way facilitates the selection and
      "binding" together of pertinent aspects of sensory stimulus into a perceived
      whole.

PMID- 16110772
TI  - Clustering of early cortical responses to median nerve stimulation from average
      and single trial MEG and EEG signals.
AB  - Median nerve electrical stimulation (MNES) produces early and strong averaged
      magnetoencephalography (MEG) or electroencephalography (EEG) signals, despite
      considerable single trial (ST) variability, demonstrated in separate MEG and EEG
      studies. Here, simultaneous MEG/EEG recordings are used to assess whether same or
      different aspects of ST variability are influencing EEG and MEG. Clustering
      techniques provided groupings for the ST timeseries for cortical responses to
      MNES derived from one modality. These groupings were applied to the corresponding
      ST timeseries derived from the other modality to quantify the similarity in
      variability captured by MEG and EEG signals. Estimates of early cortical activity
      elicited by MNES derived from MEG and EEG signals were very similar, provided
      ongoing mu rhythm was removed. Similarity between EEG and MEG estimates included
      both results based on average signals and measures of ST variability. Either MEG
      or EEG can provide a robust measure of the early cortical activity elicited by
      MNES as well as of its variability. Reliable indices of early cortical responses
      to MNES can be derived from either MEG or EEG data. These indices can be based on
      average signals, as is routinely done with clinical EEG, but it could also rely
      on hitherto little utilized measures of ST variability.

PMID- 16110773
TI  - Wavelet-crosscorrelation analysis: Non-stationary analysis of neurophysiological
      signals.
AB  - OBJECTIVE: Wavelet-crosscorrelation analysis is a new application of wavelet
      analysis used to show the propagation of epileptiform discharges and to localize
      the corresponding lesions. We have shown previously that this analysis can help
      predict brain conditions statistically (Mizuno-Matsumoto et al. 2002). Our
      objective was to assess whether wavelet-crosscorrelation analysis reveals the
      initiation and propagation of epileptiform activity in human patients. METHODS:
      The data obtained from three patients with simple partial seizures (SPS) using
      whole-head magnetoencephalography (MEG) were analyzed by the wavelet
      crosscorrelation method. Wavelet-crosscorrelation coefficients (WCC), the
      coherent structure of each possible pair of signals from 64 MEG channels
      forvarious periods, and the time lag (TL) in two related signals, were
      ascertained. RESULTS: We clearly demonstrated both localization of the irritative
      zone and propagation of the epileptiform discharges. CONCLUSIONS: Wavelet
      crosscorrelation analysis can help reveal and visualize the dynamic changes of
      brain conditions. The method of this analysis can compensate for other existing
      methods for the analysis of MEG, electroencephalography (EEG) or
      Elecotrocorticography (ECoG). SIGNIFICANCE: Our proposed method suggests that
      revealing and visualizing the dynamic changes of brain conditions can help
      clinicians and even patients themselves better understand such conditions.

PMID- 16110774
TI  - Accuracy of stereotaxic positioning of transcranial magnetic stimulation.
AB  - In cognitive neuroscience, optically tracked frameless stereotaxic navigation has
      been successfully used to precisely guide transcranial magnetic stimulation (TMS)
      to desired cortical areas for brain-mapping purposes. Thereby, potential sources
      of imprecision are the fixation of a reference frame to the head of the subject
      and the referencing procedure according to certain landmarks (LM). The aim of our
      study was to evaluate the accuracy of frameless stereotaxic coil positioning in a
      standard experimental setting. A parameter for accuracy is the reproducibility of
      LM coordinates. In order to test the stability of the referencing for stereotaxic
      positioning within a single TMS session (within-session stability), the
      coordinates of six predefined facial LM in nine subjects were recorded first
      after the initial registration and second after a 20 minutes TMS session. The two
      sets of coordinates were then compared. The reliability of the positioning
      coordinates between different TMS sessions (inter-session repeatability) was
      addressed by registering the subjects LM coordinates in two independent TMS
      sessions. The variance of the recorded coordinates was analyzed. Altogether, LM
      were registered 1728 times (192 measures per subject). Within-session stability:
      The mean Euclidean distance (MED) between the LM position coordinates before and
      after a TMS session was 1.6 mm, when pooling over all LM. Inter-session
      repeatability: The MED between the LM positions recorded after the reference
      procedures of two different sessions showed an average deviation of 2.5 mm. In
      conclusion, optically tracked frameless stereotaxic coil positioning is from the
      technical viewpoint of high stability and repeatability. It is therefore a
      precise method for TMS brain mapping studies or for repeated TMS treatments, with
      the need of topographically exact stimulation.

PMID- 16110775
TI  - Rural health care isn't lacking, researchers say.

PMID- 16110776
TI  - An update on antifungal targets and mechanisms of resistance in Candida albicans.
AB  - Much progress has been made in the last decade in identifying genes responsible
      for antifungal resistance in Candida albicans. Attention has focused on five
      major C. albicans genes: ABC transporter genes CDR1 and CDR2, major facilitator
      efflux gene MDR1, and ergosterol biosynthesis genes ERG11 and ERG3. Resistance
      involves mutations in 14C-lanosterol demethylase, targeted by fluconazole (FLZ)
      and encoded by ERG11, and mutations that up-regulate efflux genes that probably
      efflux the antifungals. Mutations that affect ERG3 mutations have been
      understudied as mechanism resistance among clinical isolates. In vitro resistance
      in clinical isolates typically involves step-wise mutations affecting more than
      one of these genes, and often unidentified genes. Different approaches are needed
      to identify these other genes. Very little is understood about reversible
      adaptive resistance of C. albicans despite its potential clinical significance;
      most clinical failures to control infections other than oropharyngeal candidiasis
      (OPC) occur with in vitro susceptible strains. Tolerance of C. albicans to azoles
      has been attributed to the calcineurin stress-response pathway, offering new
      potential targets for next generation antifungals. Recent studies have identified
      genes that regulate CDR1 or ERG genes. The focus of this review is C. albicans,
      although information on Saccharomyces cerevisiae or Candida glabrata is provided
      in areas in where Candida research is underdeveloped. With the completion of the
      C. albicans genomic sequence, and new methods for high throughput gene
      overexpression and disruption, rapid progress towards understanding the
      regulation of resistance, novel resistance mechanisms, and adaptive resistance is
      expected in the near future.

PMID- 16110777
TI  - Dermatophytes growth curve and in vitro susceptibility test: a broth micro
      titration method.
AB  - The introduction of systemic antifungal drugs which act upon different targets is
      the main issue of the in vivo antifungal resistance control. Different factors,
      such as growth curve phase, quality of the specimen, quantity of the inoculum,
      temperature, pH, culture medium composition, incubation duration and solvent, are
      believed important factors affecting minimum inhibitory concentration (MIC) value
      to most of the antifungal agents. We assayed an in vitro susceptibility test with
      40 isolates of dermatophytes: Microsporum canis, Trichophyton rubrum,
      Trichophyton mentagrophytes and Epidermophyton floccosum against griseofulvin,
      fluconazole, itraconazole and terbinafine, using the guidelines of the M38-P
      document approved by the NCCLS. We determined the growth curves, to estimate the
      specific growth rate (mu max) and the generation time (G) of each dermatophyte,
      using dry weight and spectrophotometry methods. We demonstrate that, at 192 h,
      all fungi tested had a constant growth curve and we considered this as the
      optimal time for MIC determination. Terbinafine, griseofulvin and itraconazole
      possessed the highest antifungal activity against the four groups of
      dermatophytes studied. Fluconazole demonstrated no efficacy. Our MIC results
      differ from other authors and this difference is due to the timing of the MIC
      determination based on the growth curve of each fungi tested.

PMID- 16110778
TI  - Effect of melanization upon porosity of the cryptococcal cell wall.
AB  - The cell-wall constituent, melanin, is a virulence factor for pathogenic fungi,
      but its structural and mechanistic role is not clearly understood. As
      intermediates in melanin formation are cross-linking agents, we wondered whether
      melanized cell walls might be more highly cross-linked and less porous than non
      melanized cell walls. The fungal pathogen Cryptococcus neoformans makes melanin
      only in the presence of exogenous catechols; we cultivated it with and without 1
      mmol/l dopamine. We prepared mechanically intact melanized and non-melanized cell
      walls by boiling cells in 10% sodium dodecyl sulfate; electron microscopy showed
      disruption of cytoplasm. We poured the resulting spheres into columns and studied
      the elution behavior of graded dextrans. High-molecular-weight dextrans eluted
      earlier than low-molecular-weight dextrans, which, in turn, eluted before
      glucose, behavior characteristic of size-exclusion chromatography. We calculated
      the thresholds above which the polymers were totally excluded from the cell
      walls. Melanized cells exhibited a threshold of molecular weight 30 600, non
      melanized, 270 000 (P <0.01). The corresponding Einstein-Stokes radii are 4.0 and
      10.6 nm, respectively; these represent the calculated largest pore sizes for each
      condition. We conclude that melanized cell walls are considerably less porous
      than non-melanized cell walls.

PMID- 16110779
TI  - Detection of antibodies to phospholipase B in patients infected with Cryptococcus
      neoformans by enzyme-linked immunosorbent assay (ELISA).
AB  - Secreted phospholipases are virulence factors of several fungi, including
      Cryptococcus neoformans. We describe for the first time the detection by ELISA of
      antibodies to cryptococcal phospholipase B in the serum of patients infected with
      C. neoformans or C. gattii. Sixty-nine sera from 25 patients with cryptococcosis,
      23 patients with Candida infections and 26 with bacterial or viral infections
      were tested. The sensitivity of the ELISA in patients with cryptococcosis was
      100% in immunocompetent hosts and 64.3% in immunosuppressed patients with
      cryptococcal meningitis. Absorbance readings were significantly higher in
      immunocompetent patients (P<0.001). Titres remained positive for up to 2 years.
      Positive results were noted in 10 episodes of invasive candidiasis, three
      patients colonised with Candida, and three cases of bacterial infection. Mean
      absorbance readings were significantly lower in patients with bacterial infection
      (P <0.001). We conclude that phospholipase B is produced in vivo during
      cryptococcal infection and that serum phospholipase B antibodies are a sensitive
      marker of present or past infection. Cross-reactivity of the ELISA with sera from
      patients with candidiasis indicates that common epitopes are present on
      cryptococcal and candidal phospholipase B, hence fungal phospholipase B may
      constitute a new therapeutic target.

PMID- 16110780
TI  - Development of a real-time probe-based PCR assay for the diagnosis of
      Pneumocystis pneumonia.
AB  - This paper describes the development of a rapid probe-based real-time polymerase
      chain reaction assay (PCR) for the diagnosis of Pneumocystis pneumonia. To
      develop the PCR, primers and fluorescent resonance energy transfer probes were
      designed after sequencing products obtained using previously published primers.
      This gave results that were concordant with conventional cytological staining
      techniques, but were available within 2 h instead of greater than 24 h.

PMID- 16110781
TI  - Common polymorphisms in critical genes of innate immunity do not contribute to
      the risk for chronic disseminated candidiasis in adult leukemia patients.
AB  - Chronic disseminated candidiasis is a serious fungal infection in
      immunocompromised patients, particularly those undergoing therapy for acute
      leukemia. Coordination between innate and adaptive immune system is critical to
      resistance or susceptibility to Candida infection. In order to investigate
      possible genetic contribution to chronic disseminated candidiasis of key
      molecules in the innate immune pathway, we performed a case control study using
      the candidate gene approach. Forty subjects with chronic disseminated candidiasis
      and 50 controls without chronic disseminated candidiasis but an underlying
      diagnosis of leukemia were enrolled in the Helsinki University Central Hospital
      during the period 1980-1998. Candidate genes were selected for analysis based
      upon the following criteria: a common polymorphism (>5% frequency) and existence
      a priori of clinical and biological data suggesting a role for the variant in the
      pathogenesis of chronic disseminated candidiasis. Six genes were selected from
      critical microbicidal and innate immune pathways, including three low-affinity
      Fcgamma receptors (FCGR2A, FCGR3A and FCGR3B), chitotriosidase (CHIT1), p22-phox
      NADPH oxidase (CYBA), and mannose binding lectin (MBL2). There was no
      statistically significant association of susceptibility to chronic disseminated
      candidiasis with the polymorphisms in this study. Common variants in the six
      studied genes most likely do not contribute to the risk for chronic disseminated
      candidiasis in patients with acute leukemia.

PMID- 16110782
TI  - Candida glabrata Ste11 is involved in adaptation to hypertonic stress,
      maintenance of wild-type levels of filamentation and plays a role in virulence.
AB  - The conserved family of fungal Ste11 mitogen activated protein kinase/kinases
      play important roles in several signalling cascades. We have cloned the STE11
      homologue from the fungal pathogen Candida glabrata. The C. glabrata gene is
      present in a single copy in the genome, contains a well-conserved catalytic
      domain typical of the serine-threonine protein kinases and a sterile alpha motif
      widespread in signalling and nuclear proteins. Hypothetical translation of C.
      glabrata STE11 suggests that the protein has 64% identity and 77% similarity at
      the amino acid level to Saccharomyces cerevisiae Ste11. We have shown that C.
      glabrata STE11 can complement the mating defect and partially rescue the reduced
      nitrogen starvation induced filamentation of S. cerevisiae ste11 mutants.
      Functional analysis of a C. glabrata ste11 null mutant demonstrates that Ste11 is
      required for adaptation to hypertonic stress but is largely dispensable for
      maintenance of cell wall integrity. It also plays a role in C. glabrata nitrogen
      starvation induced filamentation. Survival analysis revealed that C. glabrata
      ste11 mutants, while still able to cause disease, are attenuated for virulence
      compared to reconstituted, STE11 cells. These data suggest that C. glabrata
      Ste11, in a similar fashion to the S. cerevisiae protein, functions in a number
      of different signalling modules.

PMID- 16110783
TI  - Use of random amplified microsatellites to type isolates from an outbreak of
      nosocomial aspergillosis in a general medical ward.
AB  - Numerous patients were diagnosed with aspergillosis in a nosocomial outbreak
      caused by Aspergillus fumigatus and Aspergillus flavus. Thirty-three isolates of
      the former and 28 isolates of the latter were collected from the hospital
      environment and from the patients and studied for genetic relatedness by random
      amplified microsatellites (RAMS) analysis, in which two polymorphic regions were
      tested. Twenty-eight genotypes of A. fumigatus and 23 genotypes of A. flavus were
      identified. Four patients were infected by two isolates with the same genotype as
      the environmental isolates. One clinical genotype was shared by three patients
      and another was shared by two patients. We found that RAMS was useful for
      fingerprinting Aspergillus spp.

PMID- 16110784
TI  - Seasonal 4-year investigation into the role of the alpine marmot (Marmota
      marmota) as a carrier of zoophilic dermatophytes.
AB  - Two hundred and six samples of alpine marmot (Mamota marmota) hair (148 from
      adults and 58 from young subjects), 102 soil samples from the entrances to the
      burrows of the above individuals and 20 control specimens (obtained from
      adjoining areas away from the burrow systems where the rodents are not usually
      present) were examined from May 1994 to September 1997. Seventy-five isolates
      belonging to six species of dermatophytes were found in 69 of the 206 hair
      samples examined (33.5%). Two species were zoophilic, Microsporum canis (7.8%)
      and Trichophyton mentagrophytes (11.2.%), and four geophilic, Microsporum cookei
      (2%), M. gypseum (5.8%), Trichophyton ajelloi (3.9%) and T. terrestre (5.8%). The
      prevalence of each species in the hair samples did not change significantly
      according to year, season (chi-squared test [limit significance: P <0.05] gives
      no significant values [P>0.05] both in year and in season comparison) or age/sex
      (adult versus juvenile: P=0.1; male versus female: P=0.8) of the marmot. Twenty
      three of the 102 soil samples (22.5%) were positive for dermatophytes found in
      the hair of marmots from the same burrow systems. Five of the 20 control soil
      samples (25%) were positive for dermatophytes. One isolate of M. gypseum, three
      of T. terrestre and one of T. mentagrophytes were obtained. Compared with other
      free-ranging rodent hosts studied in Europe, this mycoflora is characterized by
      the presence and relatively high prevalence of M. canis, frequently reported in
      symptomatic and asymptomatic cats, dogs and fur animals. M. canis has not been
      isolated in other rodents in the wild. However, it has recently been reported in
      asymptomatic foxes (Vulpes vulpes) from northern Italy. The close link between V
      vulpes and M. marmota, with the former representing the most important mammal
      predator of the latter in the Alps (only a fraction of the predator's attacks
      result in the death of the rodent) may have favoured the adaptation of M. canis
      to this rodent host. The stable character of the M. canis/M. marmota relationship
      (no seasonally or annually related difference in the prevalence of this
      dermatophyte has been found) suggests the inclusion of the alpine marmot in the
      reservoir of this zoophilic pathogenic agent. In this situation, hibernation in
      labyrinthine burrow systems, where temperature and moisture ranges are quite
      uniform the whole year round, may favour the viability of M. canis arthroconidia,
      whose survival in mountain habitat might otherwise be compromised. This seems to
      be confirmed by the fact that the fungus has never been found in the control
      samples collected at a distance of 300 m from the outer edge of the sampled
      burrow systems.

PMID- 16110785
TI  - What the Aspergillus genomes have told us.
AB  - The sequencing and annotation of the genomes of the first strains of Aspergillus
      nidulans, Aspergillus oryzae, and Aspergillus fumigatus will be seen in
      retrospect as a transformational event in Aspergillus biology. With this event
      the entire genetic composition of A. nidulans, the sexual experimental model
      organism of the genus Aspergillus, A. oryzae, the food biotechnology organism
      which is the product of centuries of cultivation, and A. fumigatus, the most
      common causative agent of invasive aspergillosis is now revealed to the extent
      that we are at present able to understand. Each genome exhibits a large set of
      genes common to the three as well as a much smaller set of genes unique to each.
      Moreover, these sequences serve as resources providing the major tool to
      expanding our understanding of the biology of each. Transcription profiling of A.
      fumigatus at high temperatures and comparative genomic hybridization between A.
      fumigatus and a closely related Aspergillus species provides microarray based
      examples of the beginning of functional analysis of the genomes of these
      organisms going forward from the genome sequence.

PMID- 16110786
TI  - Reproduction in Aspergillus fumigatus: sexuality in a supposedly asexual species?
AB  - Aspergillus fumigatus has long been considered to reproduce only by asexual
      means. However, accumulating evidence suggest that a sexual stage for A.
      fumigatus may yet be identified. We describe results from published and ongoing
      studies involving population genetic analyses, genome analysis, studies of mating
      type gene presence and distribution, expression of sex-related genes, and
      taxonomic work which support the assertion that A. fumigatus has the potential to
      reproduce by sexual means. The consequences of sexual reproduction for the
      population biology and disease management of the species are discussed. The
      possible mechanisms of evolution of asexuality are then considered. It is
      proposed that asexual species may arise in one step by mutation or loss of a key
      gene(s), and/or there may be a 'slow decline' in sexual fertility within the
      species as a whole. Thus, it is argued that species should not be considered
      simply as sexual or asexual, but rather as individual isolates being present on a
      continuum of sexual fertility, with the implications for understanding
      sexuality/asexuality in A. fumigatus discussed.

PMID- 16110787
TI  - Specific molecular features in the organization and biosynthesis of the cell wall
      of Aspergillus fumigatus.
AB  - The cell wall of Aspergillus fumigatus is composed of a branched beta1,3 glucan
      covalently bound to chitin, beta1,3, beta1,4 glucans, and galactomannan, that is
      embedded in an amorphous cement composed of alpha1,3 glucan, galactomannan and
      polygalactosamin. The mycelial cell wall of A. fumigatus is very different from
      the yeast Saccharomyces cerevisiae cell wall, and in particular lacks beta1,6
      glucans and proteins covalently bound to cell wall polysaccharides. The
      differences in cell wall composition between the mould A. fumigatus and the yeast
      S. cerevisiae are also reflected at the genomic level where unique features have
      been identified in A. fumigatus. A single gene codes for the glucan synthase
      catalytic subumit; this finding has lead to the development of a RNAi methodology
      for the disruption of essential genes in A. fumigatus. In contrast to the glucan
      synthase, multiple genes have been found in the chitin synthase and the alpha
      glucan synthase families; in spite of homologous sequences, each gene in each
      family have very different function. Similarly homologous mannosyltransferase
      genes are found in yeast and moulds but they lead to the synthesis of very
      different N-mannan structures. This chemo-genomic comparative analysis has also
      suggested that GPI-anchored proteins do not have a role of linker in the three
      dimensional organization of the fungal cell wall.

PMID- 16110788
TI  - Growth control and polarization.
AB  - Filamentous fungi and yeasts both undergo polar growth. In Saccharomyces
      cerevisiae, where the mechanisms for polar growth are well-understood, polarity
      requires three steps: establishment of cortical markers specifying the site of
      bud emergence; relaying the bud site information via the Cdc42 Rho GTPase module;
      and recruitment of the morphogenetic machinery needed to remodel the cell surface
      to the specified site. Comparison of the genomes of Aspergillus fumigatus, A.
      nidulans and A. oryzae with that of S. cerevisiae show that the cortical markers
      are absent or poorly conserved, while the RhoGTPase signaling module and the
      morphogenetic machinery are highly conserved in the aspergilli. Genetic
      approaches to polarity using A. nidulans polarity mutants with defects in germ
      tube emergence (swo mutants) or branching (ahb mutants) will also be discussed.

PMID- 16110789
TI  - Intracellular and extracellular growth of Aspergillus fumigatus.
AB  - Aspergillus fumigatus is a filamentous fungus that can cause a life-threatening
      systemic mycosis in immunocompromised patients. We have studied the growth of A.
      fumigatus inside cultured cells, and the extracellular growth requirements (in
      serum). We measured the uptake of bound conidia by the cultured human type II
      pneumocyte cell line (A549) and a mouse macrophage cell line (J774). The extent
      of internalization was determined using a nystatin protection assay and by
      confocal microscopy. Both assays showed that A549 cells internalized 30% of bound
      conidia after three hours. In contrast, the value for J774 cells was 90%. In both
      J774 and A549 cells, conidia entered the endosomal pathway and ultimately co
      localized with lysosomal markers. Lysosomes containing conidia were acidified.
      Internalized conidia germinated, and after 24-36 h of incubation with A549 cells,
      the hyphal tips of some intracellular germlings became exposed to the
      extracellular space. The importance of iron acquisition to extracellular growth
      was assessed by creating a strain of A. fumigatus in which the gene encoding the
      first step of hydroxamate siderophore biosynthesis, ornithine N5-oxygenase
      (AfusidA), was inactivated by gene replacement. Mutant strains were avirulent in
      a mouse model of invasive aspergillosis indicating that siderophore biosynthesis
      is a virulence factor in A. fumigatus.

PMID- 16110790
TI  - Nitrogen metabolism of Aspergillus and its role in pathogenicity.
AB  - Aspergilli represent unique pathogens. Based on their saprophytic life style they
      are able to colonize a variety of ecological niches, among them the
      immunocompromised individual. Distinct fungal attributes that play a role in
      pathogenicity of aspergilli have been described, and primary metabolism
      indisputably has to be taken into account for contributing to the virulence
      potential of this fungal genus. Here we present an overview of studies that focus
      on this aspect of nutritional versatility. In the predominant pathogenic
      representative Aspergillus fumigatus regulation of nitrogen utilization and
      sensing of nitrogen sources have been scrutinized with respect to pathogenicity.
      The impact of distinct metabolic pathways on virulence capacities could be
      evaluated by inspection of auxotrophic mutant strains. Among them, para
      aminobenzoic acid-requiring mutants revealed that this biosynthetic route is
      strictly required for pathogenicity. For amino acid anabolism only lysine
      biosynthesis has been investigated in this regard. Fungal amino acid biosynthesis
      is generally subject to strict regulation mediated by the Cross-Pathway Control
      system, a conserved regulatory circuit evolved to counteract conditions of
      nutritional stress. A clear influence of the system on pathogenicity could be
      observed by targeting its transcriptional activator CpcA. However, additional
      metabolic characteristics as well as regulatory instruments that compensate
      environmental challenges need to be addressed in future research with the aim to
      assess the significance of fungal primary metabolism for pathogenicity of
      aspergillus species.

PMID- 16110791
TI  - A preliminary analysis of the process of protein secretion and the diversity of
      putative secreted hydrolases encoded in Aspergillus fumigatus: insights from the
      genome.
AB  - The genome sequence of Aspergillus fumigatus has enabled the annotation of genes
      likely to encode secreted enzymes that may be important in underpinning the
      natural lifestyle of the fungus and its pathogenicity. We summarize the data from
      the genome sequence relevant to both the process of protein secretion and the
      predicted hydrolase enzymes secreted by A. fumigatus.

PMID- 16110792
TI  - Incidence of invasive aspergillosis following hematopoietic stem cell and solid
      organ transplantation: interim results of a prospective multicenter surveillance
      program.
AB  - The incidence of invasive aspergillosis was estimated among 4621 hematopoietic
      stem cell transplants (HSCT) and 4110 solid organ transplants (SOT) at 19 sites
      dispersed throughout the United States, during a 22 month period from 1 March
      2001 through 31 December 2002. Cases were identified using the consensus
      definitions for proven and probable infection developed by the Invasive Fungal
      Infections Cooperative Group of the European Organization for Research and
      Treatment of Cancer and the Mycoses Study Group of the National Institute of
      Allergy and Infectious Diseases. The cumulative incidence (CI) of aspergillosis
      was calculated for the first episode of the infection that occurred within the
      specified time period after transplantation. To obtain an aggregate CI for each
      type of transplant, data from participating sites were weighted according to the
      proportion of transplants followed-up for specified time periods (four and 12
      months for HSCT; six and 12 months for SOT). The aggregate CI of aspergillosis at
      12 months was 0.5% after autologous HSCT, 2.3% after allogeneic HSCT from an HLA
      matched related donor, 3.2% after transplantation from an HLA-mismatched related
      donor, and 3.9% after transplantation from an unrelated donor. The aggregate CI
      at 12 months was similar following myeloablative or non-myeloablative
      conditioning before allogeneic HSCT (3.1 vs. 3.3%). After HSCT, mortality at 3
      months following diagnosis of aspergillosis ranged from 53.8% of autologous
      transplants to 84.6% of unrelated-donor transplants. The aggregate CI of
      aspergillosis at 12 months was 2.4% after lung transplantation, 0.8% after heart
      transplantation, 0.3% after liver transplantation, and 0.1% after kidney
      transplantation. After SOT, mortality at three months after diagnosis of
      aspergillosis ranged from 20% for lung transplants to 66.7% for heart and kidney
      transplants. The Aspergillus spp. associated with infections after HSCT included
      A. fumigatus (56%), A. flavus (18.7%), A. terreus (16%), A. niger (8%), and A.
      versicolor (1.3%). Those associated with infections after SOT included A.
      fumigatus (76.4%), A. flavus (11.8%), and A. terreus (11.8%). In conclusion, we
      found that invasive aspergillosis is an uncommon complication of HSCT and SOT,
      but one that continues to be associated with poor outcomes. Our CI figures are
      lower compared to those of previous reports. The reasons for this are unclear,
      but may be related to changes in transplantation practices, diagnostic methods,
      and supportive care.

PMID- 16110793
TI  - Clinical implications of environmental sources for Aspergillus.
AB  - Invasive aspergillosis presents a formidable problem for both diagnosis and
      therapy. Therefore, prevention is a very important strategy in controlling this
      disease. Preventing invasive aspergillosis demands a clear understanding of the
      environmental sources of Aspergillus spp. and how this mould is transmitted to
      patients. Insight into the sources of exposure, mechanisms of transmission, and
      host susceptibility to infection are vital to appropriately direct preventive
      strategies to those settings where the risk of infection is the highest and
      consequently the impact of prevention the greatest.

PMID- 16110794
TI  - Measuring environmental fungal exposure.
AB  - Airborne fungi are ubiquitous in the environment and human exposure is
      inevitable. Such fungi differ greatly in their taxonomic, physical, ecological,
      behavioral, and pathogenic characteristics. Many strategies have evolved to
      sample, identify and interpret fungal exposure and their choice is determined by
      the hypotheses involved. While fungi can be sampled directly from surfaces,
      results do not generally reflect human exposure. For this reason, airborne spores
      are commonly sampled, by either filtration or impaction, using volumetric air
      samplers. Identification is commonly performed by either culture on nutrient
      medium or light microscopy using morphological criteria, although new techniques
      using DNA probes or characteristic antigens or toxins continue to be developed.
      Interpretation of such exposure data is both complex and contentious, but while
      there are numerous recommendations there is no consensus on exposure thresholds.
      A better understanding of the complex pathogenic roles of fungi and
      susceptibilities of their hosts will enable refinement of techniques for sampling
      and interpretation.

PMID- 16110795
TI  - Aspergillosis in mammals and birds: impact on veterinary medicine.
AB  - Aspergillosis is relatively uncommon in mammals, but dogs, horses, cows and
      dolphins are susceptible. On the other hand, aspergillosis is a major cause of
      mortality in birds. This paper provides an overview of the manifestations of this
      disease in these animals. Treatment options are still lacking, but the increased
      incidence of the disease in humans has led to increased study, which may benefit
      both human and veterinary medicine.

PMID- 16110796
TI  - Aspergillus fumigatus conidial pigment and cAMP signal transduction: significance
      for virulence.
AB  - The conidial pigment of Aspergillus fumigatus contains 1,8-dihydroxynaphthalene
      (DHN)-like pentaketide melanin. It plays a major role in the protection of the
      fungus against immune effector cells; for example, it is able to scavenge
      reactive oxygen species generated by alveolar macrophages and neutrophiles. The
      polyketide synthase PKSP (ALB1) is a key-enzyme of the biosynthesis pathway; its
      structural gene is part of a gene cluster. Furthermore, the presence of a
      functional pksP (albl) gene in A. fumigatus conidia is associated with an
      inhibition of phagolysosome fusion in human monocyte-derived macrophages.
      Moreover, the analysis of mutants that are defective in elements of the cAMP
      signaling pathway found that they are almost avirulent in an optimized low dose
      murine inhalation model. Taken together, our results indicate that the cAMP/PKA
      signal transduction pathway is required for A. fumigatus pathogenicity. In
      addition, we showed that the expression of the pksP gene is, at least in part,
      controlled by the cAMP/ PKA signal transduction pathway. Currently, we
      hypothesize that pentaketide melanin is important for defence against ROS.
      However, besides its contribution to the biosynthesis of DHN-like melanin, PKSP
      also appears to be involved in the formation of another compound which is
      immunosuppressive.

PMID- 16110797
TI  - Mitogen activated protein kinases of Aspergillus fumigatus.
AB  - In microbial eukaryotes, mitogen activated protein kinase (MAPK) pathways play a
      pivotal role in regulating cellular physiology. In fungi MAPK pathways have
      established functions in mating-pheromone responses, maintaining cell wall
      integrity, responding to changes in osmolarity and nutrient sensing. We have been
      studying MAPK functions in the human pathogenic fungus Aspergillus fumigatus. The
      genome of A. fumigatus has four MAPK genes, sakA/hogA, mpkA, mpkB and mpkC.
      Deletion of the sakA gene produces a strain that does not correctly regulate
      conidial germination, sense environmental nitrogen or responds to hypertonic
      stress. The function of the remaining MAPK genes is still under investigation,
      but by analogy to work in other filamentous fungi, we speculate as to their
      possible functions in A. fumigatus.

PMID- 16110798
TI  - Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal
      nucleolus.
AB  - The ability to thrive at 37 degrees C is characteristic of all human pathogens
      and has long been suspected to play a role in the pathogenesis of aspergillosis.
      As a thermotolerant fungus, Aspergillus fumigatus is capable of growth at
      temperatures that approach the upper limit for all eukaryotes, suggesting that
      the organism has evolved unique mechanisms of stress resistance that may be
      relevant to its ability to adapt to the stress of growth in the host. High
      temperature is a strain on many biological systems, particularly those involved
      in complex macromolecular assemblies such as ribosomes. This review will discuss
      the relationship between thermotolerance and virulence in pathogenic fungi,
      emphasizing the link to ribosome biogenesis in A. fumigatus. Future work in this
      area will help determine how rapid growth is accomplished at elevated temperature
      and may offer new avenues for the development of novel antifungals that disrupt
      thermotolerant ribosome assembly.

PMID- 16110799
TI  - Aspergillus mycotoxins and their effect on the host.
AB  - Aspergillus fumigatus is known to produce various immunosuppressive mycotoxins
      including gliotoxin. However, none of these mycotoxins has been confirmed as
      being directly related to the pathogenesis of aspergilli. Recent studies have
      made substantial progress in the determination of mycotoxins as virulence
      factors. Gliotoxin was found to be produced much faster than previously believed
      under certain culture conditions, such as at 37 degrees C and under high oxygen
      content, which is close to the environment in the host. Gliotoxin was also found
      to be detectable in the sera of aspergillosis mice and of aspergillosis patients.
      Based on these findings, it is becoming evident that gliotoxin is produced in the
      infected organs of patients of aspergillosis at a significant level. In addition
      to these known mycotoxins, A. fumigatus produces many mycotoxins apparently
      different from known toxins. From the aspect of gene analysis, the deletion of
      laeA was found to block the expression of metabolic gene clusters such as
      sterigmatocystin, and the gene is also expected to be related to the production
      of gliotoxin. The significance of mycotoxins as virulence factors will hopefully
      be clarified in the near future.

PMID- 16110800
TI  - The contribution of animal models of aspergillosis to understanding pathogenesis,
      therapy and virulence.
AB  - Animal models of aspergillosis have been used extensively to study various
      aspects of pathogenesis, innate and acquired host-response, disease transmission
      and therapy. Several different animal models of aspergillosis have been
      developed. Because aspergillosis is an important pulmonary disease in birds,
      avian models have been used successfully to study preventative vaccines. Studies
      done to emulate human disease have relied on models using common laboratory
      animal species. Guinea pig models have primarily been used in therapy studies of
      invasive pulmonary aspergillosis (IPA). Rabbits have been used to study IPA and
      systemic disease, as well as fungal keratitis. Rodent, particularly mouse, models
      of aspergillosis predominate as the choice for most investigators. The
      availability of genetically defined strains of mice, immunological reagents, cost
      and ease of handling are factors. Both normal and immunosuppressed animals are
      used routinely. These models have been used to determine efficacy of experimental
      therapeutics, comparative virulence of different isolates of Aspergillus, genes
      involved in virulence, and susceptibility to infection with Aspergillus. Mice
      with genetic immunological deficiency and cytokine gene-specific knockout mice
      facilitate studies of the roles cells, and cytokines and chemokines, play in host
      resistance to Aspergillus. Overall, these models have been critical to the
      advancement of therapy, and our current understanding of pathogenesis and host
      resistance.

PMID- 16110801
TI  - Fruit flies as a minihost model for studying drug activity and virulence in
      Aspergillus.
AB  - Invasive aspergillosis (IA) is a significant cause of morbidity and mortality in
      profoundly immunosuppressed patients. The mediocre efficacy of antifungals for IA
      in clinical practice and an incomplete understanding of the pathogenesis of IA
      contribute to its overall poor prognosis. Although logistically difficult for
      large scale use, conventional animal models of IA provide valuable information
      regarding both antifungal drug efficacy and Aspergillus mutant virulence.
      However, in the era of introduction of molecular biology techniques for studying
      Aspergillus and increasing antifungal options, the existing in vivo models of IA
      might be well complemented by nonvertebrate minihost models such as the
      Drosophila melanogaster (fruit fly). Drosophila may offer the distinct advantage
      of performing fast, inexpensive high-throughput screening of compounds for anti
      Aspergillus activity and putative Aspergillus mutants for their role in
      Aspergillus virulence.

PMID- 16110802
TI  - The future of animal models of invasive aspergillosis.
AB  - The diagnosis of invasive aspergillosis remains very difficult, coupled with
      limited treatment options. Animal models have been utilized to evaluate both the
      diagnosis and treatment of infection and to assess the pathogenicity and
      virulence of the organism. However, animal models have not been standardized and
      have been used in only a limited fashion for genomic evaluation in this disease.
      Extensive efforts are underway to expand significantly the Aspergillus genomic
      information. Thus, the standardization of animal models of invasive aspergillosis
      is critical to create a unified platform to enhance evaluation of newer genomic
      information and allow assessment of pathogenicity and virulence factors. Proposed
      models, supported by a recently awarded National Institutes of Health/National
      Institute of Allergy and Infectious Diseases contract, will be developed in close
      interaction with the extended Aspergillus community (including academia and
      industry) to answer key questions in this disease. The goal of this work is to
      provide the framework to evaluate genomic targets in animal models in order to
      improve the diagnosis and treatment of invasive aspergillosis that will
      ultimately result in improved outcomes of patients with this frequently fatal
      infection.

PMID- 16110803
TI  - Advances in diagnostic testing.
AB  - Within the past decade surrogate markers have become important and reliable tools
      for the early diagnosis of invasive aspergillosis. Surrogate markers include the
      antigens galactomannan and (1 --> 3)-beta-D-glucan for which commercial assays
      are available, as well as fungal DNA for which experimental PCR assays have been
      developed. Although many clinical validation studies have been performed, the
      kinetics of these markers are still largely unknown. Recent studies have
      addressed several issues related to variables that interact with the performance
      of the assays, including exposure to mould-active antifungal agents and the
      interpretive cut-off levels. Insights gained as a result of these studies will
      help us to further optimize management strategies and to determine the optimal
      test sequence.

PMID- 16110804
TI  - Laboratory detection and identification of Aspergillus species by microscopic
      observation and culture: the traditional approach.
AB  - Molecular and immunologic tests promise better, faster laboratory diagnosis of
      aspergillosis, but microscopy and culture remain commonly used and essential
      tools. Procedural changes, as well as adequate training of laboratory
      professionals, can enhance the value of these traditional tools. Using Blankophor
      or Calcofluor for microscopic examinations; improving recognition of morphologic
      characteristics of opportunistic fungi in stained smears of specimens; maximizing
      the growth rate and production of conidia by Aspergillus spp. in culture; and
      recognizing atypical variants of common aspergilli can improve the laboratory's
      contribution to rapid diagnosis. Surveys indicate that the number of laboratory
      professionals is declining as the demand for healthcare is rising. Effective
      recruitment, retention, and training of personnel must be concurrent with
      advances in technology.

PMID- 16110805
TI  - Molecular methods for the identification of Aspergillus species.
AB  - Invasive aspergillosis (IA) is a leading cause of morbidity and mortality in
      immunocompromised hosts. In some institutions, species of Aspergillus less
      susceptible to amphotericin B than Aspergillus fumigatus are becoming more
      common, making an accurate identification of species important. However, species
      identification has traditionally relied on macroscopic colony characteristics and
      microscopic morphology, which may require several days of culture. Additional sub
      culturing on specialized media may be required to induce conidia formation; in
      some cases conidia may never form, confounding identification. Therefore, rapid,
      nucleic acid-based methods that identify species of Aspergillus independent of
      morphology are now being developed to augment or replace phenotypic
      identification methods. The most successful methods to date have employed
      polymerase chain reaction (PCR) amplification of target sequences within the
      ribosomal RNA gene complex, including the 28S ribosomal subunit (D1-D2 region)
      and the internal transcribed spacers 1 and 2 (ITS1 and ITS2 regions). We
      therefore developed a PCR-based assay to differentiate medically important
      species of Aspergillus from one another, and from other opportunistic moulds and
      yeasts, by employing universal, pan-fungal primers directed to conserved
      ribosomal genes and species-specific DNA probes directed to the highly variable
      ITS2 region. Amplicons were then detected in a simple, colorimetric enzyme
      immunoassay format (PCR-EIA). DNA sequencing of the ITS1 and ITS2 regions and of
      the D1-D2 region was also conducted for the differentiation of species by
      comparative GenBank sequence analysis. The PCR-EIA method was found to be rapid,
      sensitive, and specific for the identification and differentiation of the most
      medically important species of Aspergillus. In addition, methods to identify
      species of Aspergillus by comparative GenBank sequence analysis were found to be
      more reliable using the ITS1 and ITS2 regions than the D1-D2 region.

PMID- 16110806
TI  - Aspergillus polymerase chain reaction (PCR) diagnosis.
AB  - In recent years novel molecular methods, notably polymerase chain reaction (PCR)
      assays, have been developed to improve the diagnosis of life-threatening invasive
      aspergillosis in patients at high risk, especially patients with malignant
      hematological disease. Early diagnosis and treatment are essential for adequate
      therapeutic management. Management, however, often remains difficult since most
      of the diagnostic tools used clinically at present either lack specificity or
      acceptable sensitivity. The clinical value, advantages and remaining problems of
      PCR approaches to detect the emerging fungal pathogen are reviewed.

PMID- 16110807
TI  - The radiological spectrum of pulmonary aspergillosis.
AB  - Imaging findings in the pulmonary aspergilloses can answer important clinical
      questions. Steroid-responsive chronic asthma due to allergic bronchopulmonary
      aspergillosis can be differentiated from simple asthma by computed tomography
      (CT) evidence of extensive and severe central bronchiectasis, mucoid impaction,
      or small airways lesions. The simple aspergilloma can be differentiated from the
      complex aspergilloma by the absence of: constitutional symptoms, para-cystic lung
      opacities, cyst expansion, or progressive pleural thickening. The CT halo sign is
      a transient finding that can provide a probable diagnosis of early invasive
      pulmonary aspergillosis in patients who are at extraordinarily high risk of the
      infection. Patients with a halo sign at baseline are more likely to have a
      satisfactory treatment response than those without this indicator.

PMID- 16110808
TI  - Cytokines in host defense against Aspergillus: recent advances.
AB  - Many aspects of antimicrobial host responses are orchestrated by a complex
      network of cytokines and their receptors. This review focuses on recent progress
      in our understanding of the function of cytokines in innate immune responses to
      Aspergillus. TNF, a recognition cytokine, has been shown to be required for
      initiation of the innate response in the mouse model of invasive aspergillosis.
      Several recruitment cytokines play critical roles in mediating influx of specific
      leukocytes to the site of infection in invasive aspergillosis. Among these, the
      ELR + subset of CXC chemokines and their receptor CXCR2 are critical to
      neutrophil recruitment, while CCL3/macrophage inflammatory protein (MIP)-1alpha
      and CCL2/ monocyte chemoattractant protein (MCP)-1 are critical to recruitment of
      monocyte-lineage leukocytes and NK cells, respectively. Of the activation
      cytokines, those associated with the Th-1 phenotype, including interleukin (IL)
      12, IL-18, and interferon-gamma (IFN-gamma), are critical to protective responses
      to the infection. Conversely, the Th2-phenotype cytokines IL-4 and IL-10
      contribute to progression of infection. Modulation of the immune response to
      Aspergillus by manipulating these mediators remains intriguing as a potential
      adjunctive treatment in patients with invasive aspergillosis.

PMID- 16110809
TI  - Interaction between conidia, lung macrophages, immunosuppressants,
      proinflammatory cytokines and transcriptional regulation.
AB  - The immunosuppressive effect of dexamethasone (DEX) on macrophage killing
      activity and cytokine production in response to Aspergillus fumigatus conidia is
      antagonized by granulocyte-macrophage colony-stimulating factor (GM-CSF).
      However, the intersection of signaling pathways and the molecular mechanism of
      this antagonism remain to be defined. We postulated that DEX inhibition of NF
      kappaB was opposed by induction of IkappaB kinases (IKK) by GM-CSF + conidia
      stimulation, degradation of IkappaB, and release of nuclear factor kappa B (NF
      kappaB). This hypothesis was tested using resident peritoneal macrophages from CD
      1 mice and the murine macrophage RAW 264.7 cell line. Macrophages were
      unstimulated or stimulated with A. fumigatus conidia and simultaneously treated
      with DEX, GM-CSF or DEX + GM-CSF for 2 4 hours. IkappaB degradation in
      cytoplasmic extracts and translocation of NF-kappaB in nuclear extracts was
      measured by Western blot analysis. This showed GM-CSF reverses the
      immunosuppressive effect of DEX by enhancing the degradation of IkappaB and
      promoting the translocation of NF-kappaB to the nucleus. This would allow the
      production of proinflammatory cytokines by macrophages, facilitating resistance
      to A. fumigatus.

PMID- 16110810
TI  - Immunity to Aspergillus fumigatus: the basis for immunotherapy and vaccination.
AB  - Efficient responses to fungi require different mechanisms of immunity. Dendritic
      cells (DCs) are uniquely able to decode the fungus-associated information and
      translate it into qualitatively different T helper (Th) immune responses. Murine
      and human DCs phagocytose conidia and hyphae of Aspergillus fumigatus through
      distinct recognition receptors. The engagement of distinct receptors translates
      into disparate downstream signaling events, ultimately affecting cytokine
      production and co-stimulation. Adoptive transfer of different types of DCs
      activates protective and non-protective Th cells as well as regulatory T cells,
      ultimately affecting the outcome of the infection in mice with invasive
      aspergillosis. The infusion of fungus-pulsed or RNA-transfected DCs also
      accelerates recovery of functional antifungal Th 1 responses in mice with
      allogeneic hematopoietic stem cell transplantation. Patients receiving T cell
      depleted allogeneic hematopoietic stem cell transplantation are unable to develop
      antigen-specific T cell responses soon after transplant due to defective DC
      functions. Our results suggest that the adoptive transfer of DCs may restore
      immunocompetence in hematopoietic stem cell transplantation by contributing to
      the educational program of T cells. Thus, the remarkable furictional plasticity
      of DCs can be exploited for the deliberate targeting of cells and pathways of
      cell-mediated immunity in response to the fungus.

PMID- 16110811
TI  - Aspergillus antigens: which are important?
AB  - Aspergillus fumigatus is a ubiquitous fungus that causes a variety of diseases in
      man and animals. A number of protein, carbohydrate, and glycoprotein antigens
      have been identified from A. fumigatus. The diseases are diverse, and therefore
      are the antigens and their roles in causing or modulating the diseases. The
      induction and binding of antibodies and the interaction of antigen and various
      immune cells are of immense significance in the diagnosis and prognosis of the
      disease. In recent years, over 20 genes encoding A. fumigatus antigens have been
      cloned and the proteins expressed. Among these allergens, Asp f 1, f 2, f 3, f 4,
      and f 6 showed strong but diverse IgE binding with sera from different groups of
      patients. Results currently available suggest that Asp f 2, f 3, and f 6 together
      reacted with IgE from more patients with asthma and allergic bronchopulmonary
      aspergillosis (ABPA), although they are only marginally effective in
      demonstrating specific IgE in patients with cystic fibrosis and ABPA. The
      molecular structure of allergens also plays a major role in the immunological
      response in the allergic patients. Antigens can be engineered with less or more
      binding with IgE, and such antigens may have significant roles as specific
      reagents or as immunomodulators.

PMID- 16110812
TI  - Aspergillus and asthma--any link?
AB  - The innate immune and acquired immune responses are not separate, parallel
      systems but form interdependent components of a single integrated immune
      response. This is nicely highlighted by an expanding database demonstrating that
      the innate immune response provides the acquired immune response with information
      about the origin of the antigen and the type of response required via pattern
      recognition receptors (PRRs). Aspergillus is among a growing list of allergens
      that can aggravate asthmatic responses. Significant pulmonary pathology is
      associated with Aspergillus-induced allergic and asthmatic lung disease
      characterized by increased Th2 cytokine generation, IgE and IgG, eosinophilia,
      airway hyper-responsiveness and airway remodeling. Experimental data from a model
      of chronic fungal asthma demonstrate that thymus associated and regulated
      chemokine (TARC/CCL17) and macrophage derived chemokine (MDC/CCL22), working via
      CCR4, directly impair the innate anti-fungal immune response, thereby promoting
      the maintenance of acquired Th2-mediated asthmatic disease. Both chemokines
      appear to accomplish this by regulating the expression of PRRs such as toll like
      receptors (TLRs) and triggering receptor expressed on myeloid cells (TREM-1) by
      immune cells. Thus, the link between Aspergillus and asthma appears to reside in
      the magnitude and appropriateness of the host innate immune response, and ongoing
      research is revealing promising targets for therapy.

PMID- 16110813
TI  - Pathophysiology and immunology of allergic bronchopulmonary aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a complication of persistent
      asthma and cystic fibrosis (CF), diseases in part characterized by excessive
      viscous mucus and compromised mucociliary clearance. Inhaled conidia of
      Aspergillus fumigatus are able to persist and germinate, releasing exoproteases
      and other fungal products that further compromise clearance, breach the
      epithelium, and activate immune responses. Chemotactic cytokines (e.g. IL-8,
      RANTES, eotaxin) in particular have been implicated in murine models. Chemokine
      mediated recruitment of CD4+TH2 lymphocytes specific for A. fumigatus is a
      crucial feature of ABPA. Susceptibility also appears to involve immunogenetic
      factors including atopy and defined major histocompatibility complex-restricted
      allelic expression on antigen-presenting cells that are permissive for a TH2
      predominant immune response. Certain A. fumigatus allergens appear more
      associated with ABPA rather than simple A. fumigatus allergy. ABPA is
      characterized by marked local and systemic eosinophilia, an adaptive immune
      response with elevated levels of A. fumigatus-specific IgG, IgA and IgE
      antibodies, and a profound nonspecific IL-4-dependent elevation in total IgE.
      Clinically, ABPA manifests with recurring episodes of asthma, pulmonary
      infiltrates, and central bronchiectasis that may progress to fibrosis. It is
      treated with systemic glucocorticoids and azoles. Monitoring clinical,
      radiographic and serologic responses (especially total IgE) is essential for
      successful management.

PMID- 16110814
TI  - The invasive and saprophytic syndromes due to Aspergillus spp.
AB  - Aspergillus spp. produce a wide range of invasive and sapropytic syndromes which
      may involve any tissue. Within a given tissue or organ the pathology and
      pathogenesis varies enormously, ranging from angioinvasive disease to noninvasive
      saprophytic disease. The individual invasive and saprophytic syndromes in which a
      causative role can be attributed to Aspergillus spp. are detailed specifically
      with reference to the underlying pathology and pathogenesis, the clinical setting
      and features, and the manner in which a diagnosis can be established.

PMID- 16110815
TI  - Invasive aspergillosis in the hematologic and immunologic patient: new findings
      and key questions in leukemia.
AB  - Patients suffering from acute leukemia are at high risk for invasive
      aspergillosis and a large review and a recent clinical trial have shown that they
      represent the largest group of patients developing the disease. New host groups
      such as patients with multiple myeloma or low-grade lymphoproliferative disorders
      have contributed to an increase in the incidence of invasive aspergillosis over
      recent years. There are substantial differences in the diagnostic strategy and
      therapeutic outcome of disease between patients with a hematological malignancy
      and other host groups such as allogeneic hematopoietic stem cell transplant
      patients. Galactomannan detection ELISA test is more specific in adult patients
      with hematological malignancies than in hematopoietic stem cell transplantation
      recipients. As a result of possible improvement of the underlying immune
      deficiency upon recovery from neutropenia, survival is higher in leukemic
      patients with invasive aspergillosis than in other host groups. However, there is
      currently no evidence of an effective antifungal prophylaxis strategy against
      aspergillosis in leukemic patients. As these patients account for a majority of
      the aspergillosis cases, clinical trials on prophylaxis should not only be
      focused on allogeneic stem transplant recipients but also be designed for the
      patient with leukemia.

PMID- 16110816
TI  - New findings and key questions in hematopoietic stem cell transplantation.
AB  - Invasive aspergillosis remains the primary cause of death from infection
      following allogeneic stem cell transplantation. Most cases occur during the
      second or third month after transplantation, during graft-versus-host disease or
      immunosuppression. Strategies for management of these cases include the
      development of more effective antifungals for prophylaxis, the use of biological
      markers to improve the early diagnosis of aspergillosis, new approaches to
      transplantation to reduce the risk of infection, and the emerging area of
      targeted cellular therapy.

PMID- 16110817
TI  - Invasive aspergillosis in primary immunodeficiencies.
AB  - Primary immunodeficiencies are rare and usually first manifest during childhood.
      Invasive aspergillosis is the leading cause of mortality in chronic granulomatous
      disease (CGD), reflecting the key role of the phagocyte NADPH oxidase in host
      defense against opportunistic fungi. Despite interferon-gamma prophylaxis,
      invasive filamentous fungal infections are a persistent problem in CGD. Key
      principles of management of fungal infections involve early recognition and
      aggressive treatment and appropriate surgical debridement of localized disease.
      Because CGD is a disorder of phagocyte stem cells in which the gene defects are
      well defined, it is a model disease to evaluate immune reconstitution through
      stem cell transplantation and gene therapy. Patients with the hyper-IgE syndrome
      with recurrent infections (Job syndrome) are prone to colonization of lung
      cavities (pneumatoceles) by Aspergillus species leading to local invasion and
      rarely disseminated infection. Other primary phagocytic disorders, T-cell
      disorders, and mitochondrial disorders are uncommonly associated with invasive
      aspergillosis. Taken together, these rare primary immunodeficiencies highlight
      the complex coordination of both innate and acquired pathways mediating host
      defense against Aspergillus infection.

PMID- 16110818
TI  - New findings and unique aspects in pediatric aspergillosis.
AB  - There is a paucity of specific data on pediatric invasive aspergillosis. While
      the underlying predisposing patient diseases and treatments differ in children
      and adults, it also appears that there is a heterogeneity of invasive
      aspergillosis disease that extends to children. These aspects extend in some
      reports to the Aspergillus spp. distribution as well as the fundamental
      pathophysiology of the disease in different age groups. For instance, the newer
      diagnostic tools hold great promise for adult patients but it appears that they
      have limited usefulness in children. Only through dedicated pediatric study will
      clinicians fully discover the nuances and unique findings in children with this
      deadly disease.

PMID- 16110819
TI  - Invasive aspergillosis in organ transplant recipients: new issues in
      epidemiologic characteristics, diagnosis, and management.
AB  - Changing transplantation practices, novel immunosuppressive protocols, and
      evolving recipient characteristics have led to notable changes in the
      epidemiology of invasive aspergillosis in transplant recipients. The frequency of
      disseminated infection and of central nervous system involvement has declined
      significantly in organ transplant recipients in the recent years. Amongst
      variables that may have contributed to these trends is an overall lesser severity
      of illness of transplant recipients in the current era. Calcineurin-inhibitor
      immunosuppressive agents may also have had a role in altering the disease course
      and the risk of dissemination. A new paradigm in the management of post
      transplant immunosuppression is the use of calcineurin-inhibitor and
      corticosteroid sparing regimens by pretreatment of the recipient with T-cell
      depleting agents (Campath 1-H or thymoglobulin) and utilization of minimal post
      transplant immunosuppression. The impact of these potent lymphoablative regimens
      on opportunistic mycoses in organ transplant recipients remains to be fully
      discerned. Although still unacceptably high, the mortality rate in organ
      transplant recipients with invasive aspergillosis in the current era appears to
      have declined. A focus of a great interest and controversy is the use of
      combination therapy for invasive aspergillosis in transplant recipients.

PMID- 16110820
TI  - Nuances of new anti-Aspergillus antifungals.
AB  - Invasive aspergillosis (IA) is a serious complication of immunosuppression, and
      has become more widespread as the immunocompromised population has increased as a
      result of new treatment strategies and diseases. This paper identifies and
      discusses seven issues for managing IA and combating drug resistance. Management
      of IA requires a multifactorial approach with the host as a major contributor to
      management strategies and outcome. However, significant progress has been made,
      and with careful use of the clinical tools available it is possible to make a
      successful impact on infection outcomes.

PMID- 16110821
TI  - Long-term antifungal prophylaxis in high-risk hematopoietic stem cell transplant
      recipients.
AB  - The risks for invasive fungal infections, particularly mould infections such as
      invasive aspergillosis, among hematopoietic stem cell transplant (HSCT)
      recipients are linked to the duration and severity of myelosuppression and
      immunosuppression. Strategies to prevent invasive fungal infections have focused
      primarily on the use of orally administered azole antifungal agents during the
      neutropenic period rather than on the more prolonged post-engraftment period. The
      major limitations of these studies included the heterogeneity among the subjects
      studied for fungal infection risk factors, the agents administered, the dosing,
      and duration of prophylaxis. More recent studies have attempted to examine the
      efficacy of antifungal prophylaxis strategies among allogeneic HSCT recipients to
      day 100 and beyond. It is clear that a variety of products have efficacy in
      preventing invasive candidiasis, including imidazole and triazole antifungals,
      low-dose amphotericin B, and the echinocandin, micafungin; however, only the
      extended spectrum azole, itraconazole, has been shown to impact the incidence of
      proven invasive aspergillosis. Other extended spectrum azole antifungal agents,
      voriconazole and posaconazole, are being studied as long-term prophylaxis in high
      risk HSCT recipients. While clinical trials have suggested that a duration of
      prophylaxis against moulds of six months or more may be required, it remains
      unclear if this is required in all cases. The prophylactic efficacy over time may
      be linked to the degree of immunosuppression as measured by markers such as the
      numbers of circulating CD4 T lymphocytes. Concerns about selection for resistant
      moulds among long-term recipients of these drugs are emerging. The cumulative
      experience to date suggests that long-term antifungal chemoprophylaxis is
      feasible and effective when applied in defined circumstances. The concerns about
      treatment-related toxicities, resistance, and costs are valid.

PMID- 16110822
TI  - Aspergillosis in the CLEAR outcomes trial: working toward a real-world clinical
      perspective.
AB  - Aspergillosis is a potentially lethal infection of immunocompromised patients.
      Until 10 years ago, antifungal therapy was largely limited to amphotericin B
      deoxycholate. Perceived poor response rates and inherent toxicities with
      amphotericin B deoxycholate were a major stimulus for the development of newer
      antifungals, including lipid-formulated amphotericin B, broad spectrum azoles,
      and echinocandins. Response rates to antifungals are highly dependent on the
      underlying diagnosis and degree of immune suppression of the patient. Patients at
      highest risk of death from aspergillosis also have very high mortality rates from
      other causes as well. Outcomes reported in historical literature reviews fail to
      distinguish between overall mortality and death attributable to aspergillosis.
      While this distinction can often be difficult to assess clinically, the net
      effect is to underestimate the therapeutic success rates of antifungals. The
      CLEAR (Collaborative Exchange of Antifungal Research) project started as a post
      approval survey to monitor clinical use of amphotericin B lipid complex (ABLC).
      The scope of the CLEAR project included collection of clinical data to assess
      outcomes in patients with invasive fungal infections treated with ABLC. Clinical
      data from more than 3500 patients were entered into the CLEAR database. Outcomes
      were assessed for 509 patients with documented aspergillosis and complete data
      records. Overall response rate was 63% (cured/improved/stable) with site-specific
      response rates of 61%, 59%, and 32% for lung, sinus, and central nervous system
      infections, respectively. Solid organ transplant recipients had higher response
      rates than patients with hematological malignancies. Bone marrow transplant
      recipients had the lowest response rates. Clinical response rates with ABLC
      reported in the CLEAR trial are higher than response rates reported for
      amphotericin B deoxycholate in other trials. Since it is unlikely we will see any
      new comparative Phase III trials for aspergillosis, CLEAR-type outcome studies
      will prove useful for the foreseeable future to guide clinical management of
      aspergillosis.

PMID- 16110823
TI  - Antifungal resistance in Aspergillus.
AB  - There are currently few data on drug resistance in Aspergillus, but the recent
      development of susceptibility tests have made it possible, to some extent, to
      study resistance in azoles and polyenes. This paper reviews the limited data
      available. The increased incidence of aspergillosis and the introduction of newer
      drugs make it important to continue to monitor closely trends in antifungal drug
      resistance.

PMID- 16110824
TI  - Characterization of Aspergillus fumigatus mutants with reduced susceptibility to
      caspofungin.
AB  - Caspofungin acetate (CAS) is a member of a new class of clinically-approved
      echinocandin drugs to treat invasive aspergillosis. CAS inhibits the activity of
      beta-1,3-D-glucan synthase (GS), thus damaging the fungal cell wall. Although no
      clinical resistance of Aspergillus to CAS has been reported as yet, the
      development of in vitro reduced susceptibility is presumed to be inevitable. By
      contrast, echinocandin resistance in laboratory strains of Candida albicans and
      Saccharomyces cerevisiae has been well documented. To study the potential for
      clinical resistance in Aspergillus, two classes of Aspergillus fumigatus mutant
      strains were isolated that exhibited reduced susceptibility to CAS. In the first
      class, a site-directed mutation within the target gene (AfFKS1, encoding the
      putative catalytic subunit of GS) was introduced and shown to confer low-level
      (16-fold) reduced susceptibility. A second class of spontaneous mutants were
      sensitive to low levels of drug but displayed nearly normal growth above 0.5
      microg/ml, suggesting induction of an unknown resistance mechanism. At higher
      levels of drug (> or = 16 microg/ml), the mutants displayed partially restored
      sensitivity. Preliminary studies indicate that neither target site mutations, nor
      changes in target gene expression are present in these strains, as has been
      documented for several yeasts. Instead, preliminary results indicate that the
      molecular mechanism(s) underlying reduced susceptibility of CAS in the A.
      fumigatus strains is novel, possibly due to remodeling of the cell wall
      components.

PMID- 16110825
TI  - Azole and fungicide resistance in clinical and environmental Aspergillus
      fumigatus isolates.
AB  - Aspergillus fumigatus is a human pathogen but it is also a widespread filamentous
      fungus in the environment. A. fumigatus can therefore be exposed to antifungals
      used in medical and agricultural environments. Only the class of azoles is used
      in both of these environments (i.e. voriconazole and itraconazole in medicine;
      prochloraz, propiconazole or imazalil in agriculture). Exposure to azoles
      provides the potential for the development of resistance. Several clinical
      itraconazole-resistant isolates have been reported in A. fumigatus and their
      resistance mechanisms have been partially resolved. Since limited data exist on
      the susceptibility of A. fumigatus to both medical and agricultural antifungals,
      we undertook a drug susceptibility study including clinical (400) and
      agricultural (150) A. fumigatus isolates (Swiss origin). We tested azoles and
      also compounds of major antifungal classes used in agriculture (i.e.
      azoxystrobin, iprodione, benalaxyl or cyprodinil). The results showed that all A.
      fumigatus isolates were intrinsically resistant to iprodione, benalaxyl or
      cyprodinil (MIC90 > 32 microg x ml(-1)) and that azoxystrobin minimal inhibitory
      concentrations (MICs) showed a wide range (0.06 to 32 microg x ml(-1)). MIC
      ranges of azoles were compound-dependent. MIC90 for voriconazole, itraconazole,
      imazalil and prochloraz were within a range of 0.13 to 1 microg x ml(-1) and
      similar between clinical and environmental isolates, whereas propiconazole was
      the least active compound (MIC90: 4-8 microg x ml(-1)). Ten clinical and 36
      environmental isolates with high itraconazole MIC ( > or = 2 microg x ml(-1))
      were detected. In clinical isolates, no cross-resistance was observed between
      itraconazole and all others azoles tested. Several patterns of azole MICs were,
      however, observed in the environmental isolates. Unexpectedly, a single
      environmental isolate was voriconazole-resistant (MIC of 16 microg x ml(-1)) but
      still susceptible to itraconazole (MIC of 2 microg x ml(-1)). Taken together, our
      results demonstrate the absence of susceptibility of A. fumigatus isolates to non
      azole agricultural agents and that there is little impact of azole resistance in
      both clinical and environmental isolates. When detected, azole resistance was
      compound-specific.

PMID- 16110826
TI  - The ergosterol biosynthesis pathway, transporter genes, and azole resistance in
      Aspergillus fumigatus.
AB  - The continuous use of triazoles can result in the development of drug resistance.
      Azole-resistant clinical isolates, spontaneous and induced mutants of Aspergillus
      fumigatus have been documented. The azoles block the ergosterol biosynthesis
      pathway by inhibiting the enzyme 14-alpha-demethylase, product of the CYP51.
      Fungal azole resistance involves both amino acid changes in the target site that
      alter drug-target interactions and those that decrease net azole accumulation.
      The reduced intracellular accumulation has also been correlated with
      overexpression of multidrug resistance (MDR) efflux transporter genes of the ATP
      binding cassette (ABC) and the major facilitator superfamily (MFS) classes. About
      20 genes are involved in the A. fumigatus ergosterol biosynthesis pathway. There
      are several duplicated genes in this pathway. Interestingly, erg3 and erg11
      showed two copies in A. fumigatus. In general, Aspergillus spp. have
      proportionally more MFS transporter encoding genes than Saccharomyces cerevisiae,
      S. pombe, and Neurospora crassa. The drug H+ (12 and 14 spanners) sub-families
      are also proportionally greater than in the other species. Although the numbers
      of ABC transporter encoding genes are comparable, again the Aspergillus spp. have
      more ABC transporters related to multidrug permease than the other fungal
      species.

PMID- 16110827
TI  - Controversies concerning pathophysiology and management of acalculous biliary
      type abdominal pain.
AB  - Acalculous biliary-type abdominal pain is a commonly encountered clinical problem
      whose pathophysiology is unclear and evaluation and management are controversial.
      Cholecystokinin cholescintigraphy to measure the gallbladder ejection fraction
      (GEF) has been advocated as a criterion for cholecystectomy. However, there is no
      consensus regarding the dose and rate of infusion of cholecystokinin, both of
      which can alter the GEF, and the definition of an abnormal ejection fraction
      varies among studies. Many but not all studies have concluded that a low GEF
      predicts good outcomes after cholecystectomy, but most studies suffer from poor
      methodology and there is only one prospective randomized controlled trial. Also,
      some patients with a normal GEF have responded to cholecystectomy. Another
      controversial area has been the role of sphincter of Oddi dysfunction (SOD) in
      patients with biliary-type pain and gallbladder in situ. Some reports suggest an
      overlap between SOD and low GEF, although a causal relationship has not been
      established. Yet another subject of interest is the role of visceral hyperalgesia
      in patients with acalculous biliary-type pain. We have reviewed the relevant
      literature relating to these issues and have highlighted the controversial
      aspects. In the absence of high-quality studies, an evidence-based treatment
      algorithm is difficult to design but will be proposed. More prospective
      controlled trials are warranted to better define the appropriate evaluation and
      management of patients with this syndrome.

PMID- 16110828
TI  - Zonula occludens-1 (ZO-1) redistribution is involved in the regulation of cell
      dissociation in pancreatic cancer cells.
AB  - In our previous study, dissociation factor (DF) and mitogen-activated protein
      kinase kinase 2 (MEK2) were isolated as factors relating to cancer cell
      dissociation in pancreatic cancer cells. On the other hand, tight junction
      protein zonula occludens 1 (ZO-1) has been indicated to be involved in
      carcinogenesis. In this study, the expression of ZO-1 and a downstream kinase of
      MEK2, extracellular signal-regulated kinase 2 (ERK2), was analyzed to clarify the
      regulatory mechanism of cell dissociation in pancreatic cancer cells. Two hamster
      (PC-1.0 and PC-1) and two human (AsPC-1 and CAPAN-2) pancreatic cancer cell lines
      were used. Immunocytochemical study was performed using anti-ZO-1, ERK2, and
      phosphorylated ERK1/2 (p-ERK1/2) antibodies. DF treatment obviously disrupted ZO
      1 expression at the sites of cell-cell contact and markedly induced ERK2 and p
      ERK1/2 expression, as well as the dissociation of cell clones in PC-1 and CAPAN-2
      cells. In contrast, U0126 (a MEK1/2 inhibitor) treatment significantly induced
      the peripheral distribution of ZO-1 as well as cell aggregation in PC-1.0 and
      AsPC-1 cells, which usually grew as single cells, but seriously suppressed ERK2
      and p-ERK1/2 expression. We conclude that redistribution of ZO-1 is closely
      correlated with cell dissociation status in pancreatic cancer cells through
      activation of ERK2.

PMID- 16110829
TI  - Duct-narrowing chronic pancreatitis without immunoserologic abnormality:
      comparison with duct-narrowing chronic pancreatitis with positive serological
      evidence and its clinical management.
AB  - We reviewed the clinical features and clinical course of patients with duct
      narrowing chronic pancreatitis who were negative for immunoserologic test results
      (n = 16) in comparison with the findings for serological test-positive patients
      (n = 20) in order to determine an adequate treatment for those who had typical
      morphology of autoimmune pancreatitis in the absence of immunoserologic
      abnormality. No significant differences were found between the two groups of
      patients in clinical profiles including associated autoimmune-related diseases,
      pancreatic histology, and response to steroid therapy. Of the seronegative
      patients, eight who showed an improvement in narrowing of the main pancreatic
      duct with steroid therapy and three who did no show an improvement or who
      relapsed after surgical resection without this therapy had stenosis of the common
      bile duct with increased levels of serum hepatobiliary enzymes, except for two
      patients with affected sites limited to the body or tail of the gland. For the
      remaining five patients, who showed an improvement in pancreatic duct changes or
      long-term remission after surgery without steroid administration, normal
      biochemistry test results for liver functions were obtained, with no abnormal
      cholangiographic findings in the three patients examined. Duct-narrowing chronic
      pancreatitis without immunoserologic abnormality overlaps in clinical features
      with that fulfilling the immunoserologic criteria for a diagnosis of autoimmune
      pancreatitis. In particular, the disease with bile duct involvement should be
      treated clinically as autoimmune pancreatitis, for which steroid therapy is
      recommended, even if an autoimmune mechanism is not demonstrated serologically.

PMID- 16110830
TI  - Eosinophilic cholangiopathy--a case report.

PMID- 16110831
TI  - Diallyl trisulfide inhibits tumor necrosis factor-alpha expression in inflammed
      mucosa of ulcerative colitis.
AB  - The present study aimed to investigate the effect of diallyl trisulfide (DATS) on
      tumor necrosis factor (TNF)-alpha expression in inflammed mucosa of ulcerative
      colitis and its possible mechanism. Colonic biopsies from ulcerative colitis were
      treated with 0, 1, 5, and 10 microM DATS for 24 hr. Lactate dehydrogenase (LDH)
      activities and concentrations of TNF-alpha in supernatants were measured. mRNA
      expressions of TNF-alpha in biopsies were analyzed by RT-PCR. The expression of
      NF-kappaB P65 in tissues was studied by immunohistochemistry. Concentrations of
      TNF-alpha in supernatants of biopsies treated with 5 and 10 microM DATS were
      lower than those of untreated biopsies. There were fewer lamina propria
      mononuclear cells whose NF-kappaB P65 expression in nuclei was positive, and less
      mRNA expression of TNF-alpha in biopsies treated with 10 microM DATS than in
      untreated biopsies. There were no differences in LDH activities in supernatants
      between tissues treated with DATS and untreated tissues. DATS could downregulate
      TNF-alpha production and inhibit NF-kappaB activation in lamina propria
      mononuclear cells of inflammed mucosa, without any effect on the viability of
      colonic tissue cells.

PMID- 16110832
TI  - Characterization of functional and morphological changes in a rat model of
      colitis induced by Trichinella spiralis.
AB  - We intended to characterize the effect of inflammation on the spontaneous colonic
      motility pattern and the role of iNOS in its disruption in colitis. Colitis was
      induced by an intracolonic enema of T. spiralis larvae. Animals were studied 2-30
      days postinfection (PI). Standard H&E and iNOS staining was performed on colonic
      sections. Altered stool consistency was found from day 1 to day 21 PI;
      leukocytosis peaked on days 6-21 PI. Edema and cell infiltration were found in
      mucosa and submucosa (days 2-14 PI). Contractility displayed a disorganized
      pattern with decreased high-amplitude, low-frequency (HALF) contractions. A
      progressive fading of spontaneous activity was observed and was partly restored
      in strips devoid of submucosa. iNOS immunoreactivity increased in epithelial and
      infiltrating cells (days 2-14 PI). In this model of colonic inflammation, the
      decrease in spontaneous contractility, which might be caused by NO generated from
      mucosal and submucosal iNOS, bears some traits with changes observed in
      ulcerative colitis and might thus be useful to study the dismotility observed in
      this human disease.

PMID- 16110833
TI  - Effect of bacterial chemotactic peptides on intestinal inflammation in animal
      models of acute and chronic "relapsed" colitis.
AB  - It is known that bacterial chemotactic peptides such as formyl-methionyl-leucyl
      phenylalanine (fMLP) exacerbate colitis during the acute phase, but the precise
      role of fMLP during chronic "relapse" is unknown. In this study we examined the
      effect of bacterial peptides in animal models of acute and chronic "relapsed"
      colitis. Different parameters were evaluated, such as tissue damage,
      myeloperoxidase activity, and mucosal function. In acute trinitrobenezene
      sulfonic acid colitis, fMLP had significant adverse effects on mucosal function
      and worsened several parameters. In contrast, in chronic "relapsed" colitis the
      ability of fMLP to exacerbate the inflammation was dependent on whether it was
      confined to the lumen of the colon. Bacterial peptides such as fMLP appear to
      play a different role in the acute phase of inflammation compared with the
      chronic phase, depending on the integrity of the mucosal barrier.

PMID- 16110834
TI  - Increased beta-adrenergic sensitivity correlates with visceral hypersensitivity
      in patients with constipation-predominant irritable bowel syndrome.
AB  - Autonomic imbalance has been proposed to be a pathophysiological factor for
      irritable bowel syndrome (IBS). The aim of this study was to assess beta
      adrenergic abnormalities in IBS and to evaluate their relationship to visceral
      hypersensitivity and other symptoms of IBS patients. Sixteen IBS patients and 16
      control subjects were recruited into this study. Participants were asked to
      complete a questionnaire regarding bowel symptoms, and in order to study beta
      adrenergic sensitivity, isoproterenol stimulation tests were performed and
      visceral hypersensitivity was evaluated by barostat test. Results showed that
      beta-adrenergic activity and rectal sensitivity were more pronounced in IBS
      patients than in normal control patients (P < 0.01). Although both IBS subgroups
      also exhibited more pronounced beta-adrenergic sensitivity than did the controls
      (P < 0.05), a significant correlation between beta-adrenergic activity and
      maximally tolerable pressures on the barostat test was found only in IBS-C
      patients (P = 0.03, R = 0.855). In addition, patients with "hard or lumpy" stools
      exhibited a higher degree of beta-adrenergic activity (P = 0.00). We conclude
      that increased beta-adrenergic activity significantly correlated with visceral
      hypersensitivity in constipation-predominant IBS and symptoms of hard or lumpy
      stools in IBS patients.

PMID- 16110835
TI  - Is the prevalence of small bowel bacterial overgrowth in patients with irritable
      bowel syndrome increased? The question remains unanswered.

PMID- 16110836
TI  - Celiac disease in an adult Turkish population with type 1 diabetes mellitus.
AB  - Celiac disease is a frequent cause of morbidity among patients with type 1
      diabetes mellitus. In this study our objective was to determine the prevalance of
      celiac diasease in a Turkish adult population with type 1 diabetes mellitus.
      Patients included 122 type 1 diabetes cases from adult diabetes clinic. Total IgA
      and IgA-antiendomysial antibody (AEA) assays were performed. Patients positive
      for IgA-AEA were asked to undergo small intestinal biopsy. Of the 122 patients,
      none was IgA deficient and 3 had positive IgA-AEA results (2.45%). All three of
      these patients had biopsies diagnostic of celiac disease. The body mass index
      (BMI) values of patients with positive AEA were significantly lower than normal
      (P = 0.024). Among the gastrointestinal complaints there was an association
      between early satiety and AEA positivity (P = 0.02). None of the other
      gastrointestinal complaints or age, duration of diabetes, glycosylated hemoglobin
      values, or insulin doses used were found to be related to AEA positivity. Celiac
      disease has a high prevalence among Turkish paients with type 1 diabetes
      mellitus. Screening for IgA-AEA during routine investigations of type 1 diabetic
      patients is important to prevent celiac-associated symptoms.

PMID- 16110837
TI  - Enteral nutrition as a primary therapy for intestinal lymphangiectasia: value of
      elemental diet and polymeric diet compared with total parenteral nutrition.
AB  - Intestinal lymphangiectasia (IL) is a rare disease requiring oral fat
      restriction. The aim of this study was to evaluate the efficacy of enteral
      nutrition compared to that of total parenteral nutrition (TPN). We
      retrospectively reviewed nine patients with IL presenting with protein-losing
      enteropathy. Of these, seven patients not responding to a low-fat diet were
      treated with elemental diet (ED), polymeric diet (PD) containing medium-chain
      triglycerides, or TPN. Improvement in serum total protein was observed in two of
      three on ED and in one of two on PD, compared with three of three on TPN. Enteric
      protein loss was improved in two of two on ED, one of two on PD, and two of two
      on TPN. Outpatients who continued to receive enteral nutrition maintained a total
      protein level. Enteral nutirition appears to be as effective as TPN for patients
      with IL, and it may provide a valid and safe alternative therapy.

PMID- 16110838
TI  - Colonic Crohn's disease in children does not respond well to treatment with
      enteral nutrition if the ileum is not involved.
AB  - Data supporting a response to treatment with exclusive enteral nutrition in
      pediatric colonic Crohn's disease are few. We examined clinical and biochemical
      responses of ileal, colonic, and ileocolonic Crohn's disease and assessed the
      endoscopic and histological colonic mucosal response in the colonic and
      ileocolonic groups. We prospectively enrolled 65 children (age: 8-17 years) with
      acute intestinal Crohn's disease (Pediatric Crohn's Disease Activity Index
      [PCDAI] >20). After ileocolonoscopy, gastroscopy, and a barium meal and follow
      through, they were distributed into three groups (ileal, n = 12, ileocolonic, n =
      39; and colonic, n = 14). All patients received exclusive polymeric feed as
      treatment, with a repeat endoscopy at completion of treatment. At enrollment the
      ileal group had significantly less severe disease (P = 0.05) compared to the
      colonic and ileocolonic groups. However, the colonic disease group showed the
      least fall in PCDAI scores at completion of treatment with enteral nutrition (P =
      0.03), with the lowest remission rate (50%, vs 82.1% in the ileocolonic and 91.7%
      in the ileal group [chi2 test, P = 0.021]). Endoscopic and histologic colonic
      mucosal assessment showed a post-treatment improvement in the ileocolonic (P < or
      = 0.01) but not in the colonic disease group (P = ns). Children with disease in
      the colon respond better to enteral nutrition if the ileum is also involved. This
      may be due to different underlying inflammatory mechanisms. Detailed pretreatment
      assessment in studies of Crohn's disease according to disease distribution with
      appropriate individualized tailoring of treatment may be important in this
      regard.

PMID- 16110839
TI  - Colonic gastrointestinal autonomic nervous tumor in a patient with Crohn's
      disease.

PMID- 16110840
TI  - Gastric electrical stimulation significantly increases canine lower esophageal
      sphincter pressure.
AB  - This study determined the effect of low-frequency and high-frequency gastric
      electrical stimulation (GES) on canine lower esophageal sphincter (LES) pressure
      and also evaluated the effect of such stimulation on neurohumoral factors that
      modulate LES pressure. Eight dogs were fitted with stimulation wires along the
      greater curvature of the stomach. A sleeve device measured LES pressure before,
      during, and after GES, and regulatory peptides were measured during fasting and
      after a meal. A consistent and significant rise in LES pressure was observed
      during GES, and it was sustained after GES was discontinued. Plasma concentration
      and area under the curve of pancreatic polypeptide, motilin, gastrin and
      neurotensin were not affected by GES. We conclude that acute low- and high
      frequency GES significantly increases LES pressure. This effect may not be
      modulated by efferent vagal activity or release of regulatory peptides.

PMID- 16110841
TI  - Acid challenge to the human esophageal mucosa: effects on epithelial architecture
      in health and disease.
AB  - The histological changes that occur in the squamous epithelium in response to
      acute acid challenge was examined in healthy controls and proton pump inhibitor
      treated gastroesophageal reflux disease (GERD) patients and related to the state
      of untreated erosive GERD in a saline-controlled, randomized perfusion study. In
      the basal state a stepwise significant increase in the thickness of the basal
      cell layer, papillary length, and dilatation of intercellular spaces (DIS) was
      seen when the three groups were compared. Acid perfusion induced a slight
      increase in the height of the basal cell layer mainly in healthy volunteers; this
      layer appears to be reactive to acute acid challenge as well as to acid
      suppressive therapy. DIS increases promptly in response to acute acid exposure in
      the healthy epithelium but no changes were seen in the lengths of the papillae or
      regarding DIS in the GERD patients. A protective effect of luminal nitric oxide
      on DIS development is suggested.

PMID- 16110842
TI  - The effect of digestion of collagen and elastin on histomorphometry and the zero
      stress state in rat esophagus.
AB  - To understand the physiology and pathology of the esophagus, it is necessary to
      know the mechanical properties and their dependence on the structural components.
      The aim of this study was to investigate the effect of collagenase and elastase
      on the morphological and biomechanical properties in the no-load and zero-stress
      states in the rat esophagus. Twenty tissue rings from each esophagus of seven
      normal rats were sectioned in an organ bath containing calcium-free Krebs
      solution with dextran and EGTA. After the rings were photographed in the no-load
      state, 8 of the 20 rings were separated into mucosa-submucosa and muscle rings
      and the rings were transferred to four different solutions containing
      collagenase, elastase, or corresponding control solutions. The rings were cut
      radially to obtain the zero-stress state and photographed again. The thickness,
      area, and opening angle were measured from the digitized images. The collagen and
      elastin area fractions were determined from histological slides with Van Gieson
      and Weigert's elastic stain. The opening angles and residual strain did not
      differ in the nonseparated enzyme-treated rings and control rings. However, in
      the separated mucosa-submucosa ring the opening angle was significantly smaller
      after treatment than that in control rings (P < 0.01). Collagenase and elastase
      reduced collagen and elastin in the mucosa-submucosa layer about 40% in the
      nonseparated wall and 54% in the separated mucosa-submucosa layer (P < 0.01).
      Collagenase and elastase increased the thickness in the separated mucosa
      submucosa layer compared to the control (P < 0.05). Disconnection between the
      epithelia and the lamina propria was histologically observed after elastase
      digestion. In conclusion, collagenase and elastase caused the opening angle and
      the residual strain in the separated mucosa-submucosa layer to decrease. The
      opening angle of the separated mucosa-submucosa layer depended to some extent on
      the fraction of collagen and elastin.

PMID- 16110843
TI  - Protective effect of melatonin and omeprazole against alendronat-induced gastric
      damage.
AB  - Alendronate causes serious gastrointestinal adverse effects. We aimed to
      investigate if free radicals have any role in the damage induced by alendronate
      and if melatonin or omeprazole is protective against this damage. Rats were
      administered 20 mg/kg alendronate by gavage for 4 days, either alone or following
      treatment with melatonin or omeprazole. On the last day, following drug
      administration, pilor ligation was performed, and 2 hr later rats were killed and
      stomachs were removed. Gastric acidity and tissue ulcer index values, lipid
      peroxidation, and myeloperoxidase and glutathione levels, as well as the
      histologic appearance of the stomach tissues, were determined. Chronic oral
      administration of alendronate induced significant gastric damage, increasing
      lipid peroxidation and myeloperoxidase activity, while tissue glutathione levels
      decreased. Treatment with omeprazole or melatonin prevented this damage as well
      as the changes in biochemical parameters, and melatonin appeared to be more
      efficient than omeprazole in protecting the mucosa. Intraperitoneal
      administration of alendronate did not cause much gastric irritation. Findings of
      the present study suggest that alendronate induces oxidative gastric damage by a
      local irritant effect and that melatonin and omeprazole are protective against
      this damage due to their antioxidant properties.

PMID- 16110844
TI  - 13C-urea breath test for success of Helicobacter pylori eradication: study of
      5885 Israeli patients.
AB  - Helicobacter pylori (Hp) infection is highly prevalent in many countries and may
      cause gastritis, peptic ulcer disease, gastric cancer, and lymphoma. Successful
      eradication depends on the specific treatment used, patient compliance, and Hp
      antibiotic resistance. The primary aim was to characterize groups of patients
      with one or more failures of Hp eradication treatment. The secondary aim was to
      evaluate the factors that influence eradication failure. Between April 1, 1998,
      and December 31, 2001, 5885 patients were studied for the success of Hp
      eradication with the 13C-urea breath test (13C-UBT): 5442 after one course of
      treatment (Group I), 380 after two courses (Group II), and 63 after three courses
      (Group III). The 13C-UBT was positive in 27.8%, 37.4%, and 47.6% of patients in
      Groups I, II, and III, respectively (P(I-II) = 0.000, P(II-III) = 0.126). A
      combination of omeprazole, amoxicillin, and clarithromycin (OAC) was used in
      31.3%, 27.4%, and 7.9% of Groups I, II, and III, respectively, and a combination
      of omeprazole, amoxicillin, and metronidazole (OAM) in 15.2%, 28.9%, and 28.6%,
      respectively. Regimens that contained clarithromycin were used in decreasing
      order in Groups I, II, and III, and regimens containing metronidazole, bismuth,
      or tetracycline, in increasing order. The only good prognostic factor for
      successful eradication was Israeli origin, while European-American and Asian
      African origin, recurrence of symptoms, a history of duodenal ulcer, and chronic
      proton pump inhibitor (PPI) use did not favor successful eradication. Our results
      suggest that origin, history of peptic disease, and chronic PPI use are
      predictors of eradication failure.

PMID- 16110845
TI  - A follow-up study on the effect of Helicobacter pylori eradication on the
      severity of gastric histology.
AB  - Helicobacter pylori genetic diversity and geographic distribution affect the
      severity of gastric histology; while eradication heals gastritis, the improvement
      of atrophy and intestinal metaplasia (IM) is still controversial. We investigated
      whether H. pylori infection and genotypes (cagA-vacA) influence the histological
      changes and whether eradication resolves these changes. Twenty-one patients (11
      duodenal ulcer, 2 gastric ulcer, 8 gastritis) received treatment. Biopsies for
      CLO, PCR, histology, and culture were collected before and at 1 and 12 months
      after treatment, and serum samples at 0, 1, 2, 6, and 12 months. H. pylori
      eradication was achieved in 71% of the patients. Histological scores for H.
      pylori densities were significantly higher in the antrum and incisura angularis.
      Scores for mononuclear cell and neutrophil infiltration were significantly higher
      in regions with a high H. pylori density and improved progressively after
      eradication. Eight patients with atrophy including five with IM showed no
      significant changes 12 months after eradication. The cagA gene, detected in 13
      (62%), the vacA-sla gene, in 20 (95%), and the vacA-m1 gene, in 12 (57%) of 21
      patients were significantly associated with duodenal ulcer. A gradual decline in
      antibody titer reached an average of 67% 12 months after eradication. H. pylori
      infection and the associated genotypes (cagA of Western type) affect the severity
      of the gastric histology (mild forms of atrophy and IM) and the disease outcome.
      Eradication of H. pylori resulted in healing of gastritis, but with no
      significant improvement in atrophy or IM.

PMID- 16110846
TI  - A replaced right hepatic artery and a large duodenal polyp in attenuated familial
      polyposis.

PMID- 16110847
TI  - Immunization needs of chronic liver disease patients seen in primary care versus
      specialist settings.
AB  - Chronic liver disease patients may benefit from certain vaccines, but their
      immunization coverage levels have not been widely studied. We examined the
      serologic and vaccination status of 693 chronic liver disease patients from 37
      primary care and specialist centers. Patients in primary care had more often
      received influenza (47 versus 32%; P < .001) and pneumococcal (39 versus 19%; P <
      .001) vaccines. Among patients without documented prior exposure, those seeing
      specialists had more often completed hepatitis A (28 versus 5%; P < .001) and
      hepatitis B (29 versus 14%; P < .001) vaccination. Coverage was higher in centers
      with a policy of vaccinating on-site, among non-Hispanic whites, and among
      patients with hepatitis C and cirrhosis. In summary, most patients were
      unprotected against one or more vaccine preventable diseases. The higher coverage
      rates evident in centers vaccinating on-site suggests a breakdown may occur when
      patients are referred to alternative vaccination venues.

PMID- 16110848
TI  - An unusual cause of acalculous cholecystitis during pregnancy: hepatitis A virus.

PMID- 16110849
TI  - Dramatic response to granulocytapheresis in a Crohn's disease case complicated by
      hepatitis C virus.

PMID- 16110850
TI  - Vanishing bile duct syndrome and inflammatory pseudotumor associated with a case
      of anabolic steroid abuse.

PMID- 16110851
TI  - Evaluation of endoscopic variceal ligation (EVL) versus propanolol plus
      isosorbide mononitrate/nadolol (ISMN) in the prevention of variceal rebleeding:
      comparison of cirrhotic and noncirrhotic patients.
AB  - Both EVL and drug therapy are effective in the prevention of variceal rebleeding.
      Comparisons between the two modalities are few, and only in cirrhotics. This
      prospective randomized controlled trial compared EVL with drug therapy
      (propranolol + ISMN) in the prevention of rebleeds from esophageal varices in
      cirrhotic and noncirrhotic portal hypertension (NCPH) patients. One hundred
      thirty-seven variceal bleeders were randomized to EVL (Group I; n = 71) or drug
      therapy (Group II; n = 66). In Group I, EVL was done every 2 weeks till
      obliteration of varices. In Group II, propranolol (dose sufficient to reduce
      heart rate to 55 bpm/maximum tolerated dose) and ISMN (incremental dose up to 20
      mg BD) were administered. Group I and II patients had comparable baseline
      characteristics, follow-up (12.4 vs. 11.1 months), cirrhotics and noncirrhotics
      [50(70.4%) and 21(29.6%) vs. 51(77.3%) and 15(22.7%)] and frequency of Child's A
      (35 vs. 27), B (26 vs. 28), and C (9 vs. 11). The mean daily dose was 109 +/- 46
      mg propranolol and 34 +/- 11 mg ISMN and was comparable in cirrhotic and NCPH
      patients. Upper GI bleeds occurred in 10 patients in Group I (5 from esophageal
      varices) and in 18 patients in Group II (15 from esophageal varices) (P = 0.06).
      The actuarial probability of rebleeding from esophageal varices at 24 months was
      22% in Group I and 37% in Group II (P = 0.02). The probability of bleed was
      significantly higher in Child's C compared to Child's A/B cirrhotics (P = 0.02).
      On subgroup analysis, in NCPH patients, the actuarial probability of bleed at 24
      months was significantly lower in Group I compared to Group II (25% vs 37%; P =
      0.01). In cirrhotics, there was no difference in the probability of rebleeding
      between patients in Group I and those in Group II (P = 0.74). In Group II, 25.7%
      patients had adverse effects of drug therapy and 9% patients had to stop
      propranolol due to serious adverse effects, none required stopping ISMN. There
      were 10 deaths, 6 in Group I (bleed related, 1) and 4 in Group II (bleed related,
      1); the actuarial probability of survival was comparable (P = 0.39). EVL and
      combination therapy are equally effective in the prevention of variceal
      rebleeding in cirrhotic patients. EVL is more effective than drug therapy in the
      prevention of rebleeds in patients with NCPH and, hence, recommended. However, in
      view of the small number of NCPH patients, further studies are needed before this
      can be stated conclusively.

PMID- 16110852
TI  - Mucosal prolapse polyp arising on the anastomotic site or postpolypectomy site of
      the rectum endoscopically mimicking recurrence of adenocarcinoma.

PMID- 16110853
TI  - Pedunculated angiodysplasia of the colon treated with endoscopic resection: a
      case report.

PMID- 16110854
TI  - Duodenal acid clearance in humans: observations made with intraluminal impedance
      recording.
AB  - Duodenal acid clearance appears to be involved not only in the pathogenesis of
      duodenal ulcer disease but also in functional dyspepsia. Duodenal contractile
      activity can help to maintain neutral pH in the duodenum by mixing acid with
      bicarbonate or by aborally transporting the acid load. Intraluminal impedance
      recording, allowing the detection of nonacid liquid boluses, can be carried out
      concomitantly with antroduodenal manometry and pH recording and may thus provide
      useful information about the mechanisms involved in duodenal clearance of
      endogenous acid and volume boluses. Eight H. pylori-negative healthy volunteers
      were studied with two catheters positioned across the pylorus, allowing the
      recording of five impedance signals (one antral, one pyloric, and three duodenal)
      simultaneously with six pressure signals (two antral, one pyloric, and three
      duodenal) as well as distal antral and proximal duodenal pH. During phase II of
      the migrating motor complex, which is known to be associated with the highest
      duodenal acid exposure, each duodenal acidification event (defined as a pH drop
      >2 pH units) was characterized by its maximal amplitude, duration, temporal
      relationship with antroduodenal manometric events, and relation to impedance
      variations. Acid was considered to have been cleared from the duodenum when the
      preacidification pH was restored (+/-0.2 unit). A total of 164 duodenal pH drops
      were recorded during the 323 min of phase II recordings. Eleven percent of the
      duodenal acidification events were short-lived (<10 sec). All of these events
      were temporally associated with a propagated antroduodenal contraction and a
      short-lived drop in impedance, suggesting rapid aboral passage of the acid bolus.
      The long-lived duodenal acidification events lasted a mean of 32 sec (range, 25
      66 sec). In 90% of these events an antroduodenal propagated contraction was
      recorded at the time of onset. Repetitive duodenal contractions followed the
      onset of the long-lived acidification events in 34% of the cases. These remained
      present until complete clearance of the acid. In 81% of the long-lived
      acidification events, recovery of the associated impedance drop occurred
      simultaneously with the pH recovery, suggesting a complete clearance of the
      bolus. Less frequently (19%), the duodenal pH recovered while the impedance
      remained low, suggesting that the bolus was not cleared but neutralized.
      Interdigestive duodenal acidification events usually last about 30 sec. They
      evoke duodenal contractions in only one-third of cases. Combined pH and impedance
      recording makes it possible to distinguish between neutralization of acid boluses
      and their complete total clearance.

PMID- 16110855
TI  - [Identification of Fritillaria herbal drugs by X-ray diffraction of starch
      grains].
AB  - OBJECTIVE: To provide a simple method to identify different of herbal drugs of
      Fritillaria. METHOD: The X-ray diffraction spectra of five Fritillaria powders
      were obtained by X-ray diffractometry (XRD). RESULT: By analyzing the diffraction
      peaks of starch over the 2theta diffraction angle in the range of 10 degrees-30
      degrees, we concluded that the crystal type of starch in F. thunbergii, F.
      ussurensis, F. pallidifloca and F. hupehensis was B-type. However, the crystal
      type of starch in F. cirrhosa was CB-type. The degree of crystallinity of starch
      was 42.1%, 43.6%, 37.7%, 35.9% and 30.8%, corresponding to F. thunbergii, F.
      ussurensis, F. pallidiflcoca,F. cirrhosa and F. hupehensis. CONCLUSION: Based on
      the differences of crystallinity of starch and X-ray diffraction spectra of
      Fritillaria powders, different species of Fritillaria can be identified.

PMID- 16110856
TI  - [Study on the optimal harvesting time of Rumex gmelini by analyzing the contents
      of principal components].
AB  - OBJECTIVE: To establish a method used for optimization of harvesting time and
      determine the best time for harvesting Rumex gmelini. METHOD: An HPLC method was
      applied to determinate the contents of seven active constituents(resveratrol,
      polydatin, chrysophanol 1-glucoside, nepodin, emodin, chrysophanol and
      physcion)of R. gmelini at different development stage. The result was analyzed by
      principal component analysis. RESULT: The accumulation of active constituents
      showed a regular pattern. CONCLUSION: The best harvesting time of R. gmelini is
      early July.

PMID- 16110857
TI  - [Study on tissue culture and plant regeneration of Nervilia fordii].
AB  - OBJECTIVE: Tissue culture of Nervilia fordii to get its regeneration. METHOD:
      Effects on indusement of rhizoma and plant regeneration of different implants,
      density of hormones, additives were studied. RESULT: The best implant was conn.
      Effect of 6-BA 2 mg x L(-1) were better than 6-BA 1 on rhizoma reducing. The
      coconut juice and active carbon could increase the growth of rhizoma. CONCLUSION:
      Bud could be induced on 1/2MS + 6-BA 2 mg x L(-1) by inoculating corm on culture
      mediem, and could grow lots of rhizoma after inoculating on the culture mediem
      containing 10% coconut juice and 1 per thousand active carbon. The white rhizoma
      could be induced to corms and regeneration plants on 1/2MS + 1 per thousand
      active carbon. The green rhizoma could be induced directerly to regeneration
      plants on 1/2MS + 6-BA 2 + NAA 2.

PMID- 16110858
TI  - [Tissue culture and plantlet regeneration from embryo of Saussurea involucrate].
AB  - OBJECTIVE: To establish a protocol of rapid clonal propagation of Saussurea
      involucrate by using embryo as explants. METHOD: MS medium was used as basal
      medium and BA and NAA were supplemented to find out the optimal hormone
      combinations for adventitious buds initiation, adventitious bud multiplication
      and rooting. RESULT: All embryo explants started to grow adventitious buds within
      45 days when they were cultured on the media supplemented with 0.02-0.1 mg x L(
      1) NAA and 2 mg x L(-1) BA; The adventitious buds multiplicated within 30 days
      when they were transferred to the media containing 0.1-0.2 mg x L(-1) NAA and 2-3
      mg x L(-1) BA; 92% of the adventitious buds rooted well after they were planted
      on the MS medium containing macroelements at half strength and 0.4 mg x L(-1) NAA
      for 25 days. The regenerated plantlets grew well after they were transplanted and
      the survival rate was up to 70%. CONCLUSION: Plantlets of S. invducrate
      regenerated high frequence through adventitious bud.

PMID- 16110859
TI  - [Study on liver targeted drug delivery system of the effective anticancer
      component from Bolbstemma paniculatum].
AB  - OBJECTIVE: To study the liver targeted drug delivery system of TBMS--the
      effective anticancer component from Bolbstemma paniculatum, and to discuss the
      system's function of decreasing toxicity. METHOD: BCA was used as carrier
      material. The preparation through overall feedback dynamic techniques. The
      properties of preparation and toxicology were also technology of nanoparticles
      was optimized studied. Thenanoparticles' targeting in mice vivo was observed with
      transmission electron microscopy. The function of decreasing toxicity was
      researched by the XXTX-2000 automatic quantitative analysis management system.
      RESULT: D50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and
      88.6% respectively. The release in vitro accorded with Weibull equation. The
      reaching release balance time and the t 1/2 extended 26 times and 19 times
      respectively comparing with injection. Nanoparticles mainly distributed in liver
      tissue. Their toxicity to lung and liver was evidently lower than injection.
      Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much
      lower than injection. CONCLUSION: The TBMS can be targeted to liver by liver
      targeted drug delivery system. At the same time, the problem about the toxicity
      hindering clinical application could be solved, which lays the foundation for the
      further studies on TBMS.

PMID- 16110860
TI  - [Studies on the nasal epithelium toxicity of adjuvants and recombination hirudin
      (rHV2) nasal spary].
AB  - OBJECTIVE: To investigate the nasal epithelium toxicity of adjuvants and rHV2
      nasal spary(HVS). METHOD: Ciliary movement were evaluated with in situ toad
      palate model; The histology assessment of nasal epithelium were carried out after
      long-lasting and repeated use of HVS. RESULT AND CONCLUSION: Adjuvants included
      SDS, Brij 35, azone, lecithin, EDTA, menthol, nipagin and thiomersal were able to
      significantly inhibited the ciliary movement, while tween80, glycyrrhizic acid
      monoammonium salt, benzalkonium bromide, sodium benzoate and adhensive materials
      investigated had less influence on it. HVS was able to damaged the nasal
      epithelium, but this effect recovered soon after stopping administration. It was
      demonstrated that SDS, Brij 35, azone,lecithin, EDTA, menthol, nipagin and
      thiomersal. It had significant cilitoxity, while tween80, glycyrrhizic acid
      monoammonium salt, benzalkonium bromide, sodium benzoate and adhensive materials
      investigated had no significance; Chitosan co-administration with some adjuvants
      may make the cillitoxity severer; It is available that rHV2 be administered by
      nasal spary.

PMID- 16110861
TI  - [Experimental studies on the preparation techniques of Tongjingshu babu sticking
      plaster].
AB  - OBJECTIVE: to establish the optimum preparation procedure for Tongjingshu babu
      sticking plaster. METHOD: Orthogonal design was used to observe the adhesion
      power, cohesion by the multi-electronic experimental equipment. RESULT: The best
      formulation is composed of ointment, polypropylene acid, glycerin, bond and its
      proportion is 0.2:4:8:1.2, the final plaster contains 35% water with idea
      stability to the skin. CONCLUSION: The formulation of Tongjing-shu babu sticking
      plaster is resonable and its preparation is simple and rapid.

PMID- 16110862
TI  - [Chemical constituents in roots of Polygala fallax and their anti-oxidation
      activities in vitro].
AB  - OBJECTIVE: To study the chemical constituents in roots of P. fallax and their
      anti-oxidation activities in vitro. METHOD: Column chromatographic techniques
      were employed for isolation and purification of chemical constituents of the
      plant. The structures were elucidated on the basis of the spectral evidence and
      the physical and chemical character. The isolated compounds were screened with
      four anti-oxidation models in vitro. RESULT: Seven xanthones, 1,7-dihydroxy-2,3
      methylenedioxyxanthone (1), 1-methoxy-2,3-methylenedioxyxanthone (2), 3-hydroxy
      1,2-dimethoxyxanthone (3), 1,6,7-trihydroxy-2,3-dimethoxyxanthone (4), 7-hydroxy
      1-methoxy-2,3-methylenedioxyxanthone (5), 1,3-dihydroxy-2-methoxyxanthone (6) and
      1,3,7-trihydroxy-2-methoxyxanthone (7), were isolated from the roots of P.
      fallax. And compounds 1 - 7 showed different anti-oxidation activities in the
      different pharmacological models. CONCLUSION: Compounds 2, 3, 5 and 7 were
      isolated from this plant for the first time. Xanthones from this plant showed
      anti-oxidation activities. The pharmacological activities of the pure compounds
      from this plant were also reported for the first time.

PMID- 16110863
TI  - [Study on chemical constituents in seeds of Helicia nilagirica (II)].
AB  - OBJECTIVE: To study the chemical constituents in seeds of Helicia nilagirica.
      METHOD: The ethanol extract was seperated by petroleum ether, dichloromethane, n
      butanol in sequence, then isolated by silica gel column chromatography. The
      structures were identified and elucidated by physicochemical properties and
      spectral analysis. RESULT: Five compounds were isolated from the dichloromethane
      and n-butanol extracts, identified as p-hydroxybenzaldehyde (1), p-hydroxybenzoic
      acid (2), gallic acid (3), helicide (4), 4-formylpymyl-O-beta-D-glucopyranoside
      (5). CONCLUSION: All the compounds except IV were isolated from the plant for the
      first time. The compounds I, II and III were isolated from the genus Helicia for
      the first time.

PMID- 16110864
TI  - [Coumarins from root of Zanthoxylum dimorphophyllum var. spinifolium].
AB  - OBJECTIVE: To study the chemical components from dried roots of Zanthoxylum
      dimorphophyllum var. spinifoliun. METHOD: The chemical components were isolated
      by low pressure column chromatography and their structures were identified by
      spectroscopic methods. RESULT: Five compounds were isolated and identified as 6
      (2', 3'-dihydroxy-3'-methyl-butyl)-7-hydroxy-5-methoxy-2H-1-benzopyran-2-one (I),
      6-(2',3'-dihydroxy-3'-methyl-butyl)-7-methoxy-8-(3'-methyl-but-2'-enyl)-2H-1
      benzopyran-2-one (II),6-(2',3'-dihydroxy-3'-methyl-butyl)-7-hydroxy-2H-1
      benzopyran-2-one (III), 6-(2', 3'-oxiranyl-3'-methyl-butyl)-7-methoxy-8- (3
      methyl-but-2-enyl)-2H-1-benzopyran-2-one (IV), 7-methoxy-8-(3'-methyl-but-2'
      enyl)-2H-1-benzopyran-2-one (V). CONCLUSION: These compounds were isolated from
      the plant for the first time.

PMID- 16110865
TI  - [Affection of different preparations on the content of toxic constituents in
      traditional Chinese medicines, examplified with Caulis Aristolochiae
      Manshuriensis].
AB  - OBJECTIVE: Taking Caulis Aristolochiae Manshuriensis (Guanmutong in Chinese,
      derived from the stem of Aristolochia manshuriensis) as an example, to study the
      affection of different preparations on the content of toxic constituents in
      traditional Chinese medicines. METHOD: The separation was performed on a zorbax
      SB-C18 column with mobile phase of acetonitrile-3.7 mmol x L(-1) phosphoric acid
      buffer, detected at 260 nm. RESULT: The extraction percentage of aristolochic
      acids I, II and IV a in water extraction (1 h x 2) of Guanmutong were 53.4%,
      75.5% and 61.9%, respectively; the remaining quantity of aristolochic acids I, II
      and IVa in the dregs of the decoction were 22.3%, 15.7% and 30.3%, respectively;
      Aristolochic acid I was still main substance among these aristolohic acids in the
      decoction of Guanmutong. CONCLUSION: The content of toxic constituents of the
      traditional Chinese medicines varies evidently with different preparations of
      Guanmutong. So the preparation methods of traditional Chinese medicines should be
      suitably selected according to characteristics of the toxic constituents so as to
      lessen the body damages of human.

PMID- 16110866
TI  - [The determination of echinacoside and acteoside in herbs of Cistanche tubulosa].
AB  - OBJECTIVE: To analyse the echinacoside and acteoside content of Cistanche
      tubulosa, collected from different hosts and different size of the cultivated,
      which is compared to the wilding by RP-HPLC method. METHOD: An Agilent Eclipse
      XDB-C18(4.6 mm x 250 mm, 5 microm) column was used and a mixture of methanol
      acetonitrile-1% acetic acid (15:10:75) was used as the mobile phase at a flow
      rate of 0.6 mL x min(-1). The column temperature was 30 degrees C and the UV
      detection wavelength was 334 nm. RESULT: The calibration curves of echinacoside
      and acteoside were in good linearity over the range of 0.904-9.04 microg (r =
      0.999 9), and 1.27-12.7 microg (r = 0.999 9) respectively and the average
      recoveries of echinacoside (and acteoside) were 98.9% (n = 5, RSD 1.9%), and
      97.0% (n = 5, RSD 0.97%). CONCLUSION: The method is simple, quick, acurate. In
      all of the samples, the contents of echinacoside is markedly more than that of
      acteoside, the content of the two active component in the wilding is higher than
      that in the planting. The content of sample in the different sizes gradually
      increase from the big to the small, and the contents of samples collected from
      the different hosts vary markedly. These results are useful for the quality
      evaluation of medicinal materials of C. tubulosa.

PMID- 16110867
TI  - [Experimental study on antidiabetic effect of the total flavonoids in Leucaena
      seeds].
AB  - OBJECTIVE: To study the hypoglycemic effect of the total flavonoids in Leucaena
      seeds(TF). METHOD: Experimental observation was performed by using various
      diabetic mice induced by alloxan, adrenalin, etc. RESULT: TF could significantly
      lower the blood glucose levels in Alloxan model mice, adrenalin model mice and
      hyperglycemic mice, while had no hypoglycemic effect on the normal mice.
      CONCLUSION: The total flavonoids in Leucaena seeds has hypoglycemic effect in
      diabetic model mice.

PMID- 16110868
TI  - [Protective effects of San Baoxin on injury induced by myocardical ischemic
      reperfusion and anti-thrombosis in rats].
AB  - OBJECTIVE: To investigate the effects of San Baoxin on myocardial injury induced
      by ischemia-reperfusion (MI/R) and thrombogenesis in rats in vivo and ex vivo.
      METHOD: The experimental model was established by ligation of left anterior
      descending coronary artery for 30 min followed by reperfusion for 180 min. The
      Chandler method was used to produced ex vivo thrombosis and an electrical
      stimulation of common carotid artery was adopted to form in vivo thrombosis
      respectively, the effect of antithrombosis induced by San Baoxin was observed.
      RESULT: San Baoxin significantly decreased the content of malondialdehyde (MDA),
      obviously elevated the activity of superoxide dismutase (SOD) and increased the
      amount of NO of the serum simultaneously. The San Baoxin at the dosage of 10 g x
      kg(-1) could remarkably lengthen the OT ( P < 0.05). All San Baoxin dosages could
      inhibit the formation of ex vivo thrombosis. CONCLUSION: San Baoxin protects the
      myocardium from injury of ischemic and reperfusion. The protective effect of San
      Baoxin may be due to that it can dilate vessels, increase the activity of
      clearance enzyme of free radical and inhibit lipid peroxidation and the formation
      of ex vivo and in vivo thrombosis.

PMID- 16110869
TI  - [Research on cytokines gene express of rats alcoholic liver disease affected by
      tea polyphenol].
AB  - OBJECTIVE: To evaluate the effect of tea polyphenol(TP) on the rat with alcoholic
      liver damage. METHOD: Rats were divided into 3 groups, in which 2 groups were
      stomach perfused with alcohol to result in ALD, and 1 group of them stomach
      perfused with TP simultaneously. Another group was normal control groups (stomach
      perfused with drinking water). In the end of 12 weeks, the liver specimen of each
      rat was observed by anglicizing its tissue damage, and all data collected was
      performed by statistical analysis in quantum and semi-quantum. Meanwhile
      cytokines gene express of each group is determined. RESULT: In the end of 12
      weeks, alcoholic hepatitis appeared in rat liver. Hepatic injury in alcohol group
      and TP group were found, but could not be found in normal group. Compared with
      pure alcohol group, alcoholic liver damage mainly showing with steatosis in TP
      group were slight, in addition showing liver cellular swelling with small area,
      with less spot and focal necrosis, none bridging necrosis. Steatosis were slight
      relatively, mega-bubble steatosis were less found. Collagen deposition of TP
      group were less than those of pure alcohol group. Gene expression of. cytokine
      have diversity statistically such as IL-3, IL-4, IL-1R2, IL-6R, IL-7R2, IL-3Ra,
      IL-R1, IL-13, IL-1R1, IL-7R2, EPO-R, LIFR, IL-1R2, IL-5R2, CSF1, CD27, IL-6R.
      CONCLUSION: TP is able to attenuate alcoholic liver damage. It's mechanism is
      possibly due to modulating cytokines gene expression of cytokine.

PMID- 16110870
TI  - [Purification and characterization of the proliferation of rat osteoblast-like
      cells UMR-106 from pilose antler].
AB  - OBJECTIVE: The activity of deer serum albumin on proliferation of rat osteogenic
      like cells UMR-106 and the IGF-I secretion were investigated in order to
      elucidate pilose antler's bone-strengthening mechanism. METHOD: Deer serum
      albumin was isolated from freeze-dry pilose antler powder extract. The methods
      were Sephacryl S-200HR gel filtration, POROS 20QE ion-exchange and TSK G3000SW
      chromatographies. The effect of deer serum albumin on proliferatio of UMR-106
      cells was assaied by MTT, and the secretion of IGF-I of UMR-106 cells was assaied
      by RIA. RESULT: Deer serum albumin, with the molecular weight of 56.3 kDa,
      significantly increased the proliferation rate of the osteoblast-like UMR-106
      cell and IGF-I secretion. When concentration of deer serum albumin reached 0.149
      microg x mL(-1), UMR-106 cell proliferation rate was 241.03% and IGF-I secretion
      was 66.89 ng x mL(-1). CONCLUSION: The concentration of deer serum albumin, from
      14.9 ng x mL(-1) to 14.90 microg x mL(-1), significantly increased the
      proliferation rate of the osteoblast-like UMR-106 cell and IGF- I secretion.

PMID- 16110871
TI  - [Protective effect of purariae isoflavone on apoptosis cells of nasal mocosas in
      ovariectomized rats].
AB  - OBJECTIVE: To study the protective effect of purariae isoflavone on apoptosis
      cells of atrophic nasal mucosas in ovariectomized rats. METHOD: 60 rats were
      divided into four groups as control, ovariectomized, ovariectomized + nylestriol
      (O + N) and ovariectomized + purariae isoflavone (O + P), each with 15 rats.
      Earlier apotosis cells of mucosas taken from nasal septum were measured with flow
      cytometry. RESULT: Compared with control group, and the number of apoptosis cells
      of mucosas increased after being ovariectomized,and the number of apoptosis cells
      of mucosas in O + N and O + D group didn't change. CONCLUSION: Nylestriol and
      purariae isoflavone might have effects on protecting cells of mucosas from
      lacking of estrogen by decreasing apoptosis cells in ovariectomized rats.

PMID- 16110872
TI  - [Effects of compositions of Mahuang decoction on chemotaxis and leukotriene
      production from neutrophils in rats].
AB  - OBJECTIVE: To explore the regularity of recipe composition by observing
      inhibitory effects of disassembled compositions of Mahuang decoction (MHD) on
      chemotaxis and leukotriene production from neutrophils in rats. METHOD:
      Neutrophil aggregation was induced by intraperitoneal injection of glycogen in
      rats. Intraperitoneal lavage fluid (PLF) was collected and neu-trophils were
      removed. Neutrophils were stimulated by calciumionophore A23187 in vitro to
      produce leukotriene B4. The concentrations of leukotriene B4 was measured by
      reversed-phase high performance liquid chromatography(HPLC), chemotatic chamber
      assay was used to investigate the regulative role of MHD on chenmotaxis of the
      neutrophils in response to LPS stimulation. RESULT: Disassembled compositions of
      MHD could inhibite chemotaxis and leukotriene production from neutrophils in
      rats. Inhibitory effects of MHD on mast cells were different. CONCLUSION: MHD has
      significantly inhibitory effects on chemotaxis and leukotriene production from
      neutrophils in rats. The original formula (MHD) works best. These results have
      confirmed the rationality and scientific level of MHD.

PMID- 16110873
TI  - [Effect of l-tetrahydropalmatine on expression of adhesion molecules induced by
      lipopolysaccharides in human umbilical vein endothelium cell].
AB  - OBJECTIVE: To investigate the effect of l-tetrahydropalmatine (l-THP) on adhesion
      molecule expression induced by LPS in human umbilical vein endothelium cell
      (HUVEC). METHOD: HUVEC were obtained from the human umbilical cord vein and
      treated by LPS or LPS plus different concentration of l-THP. Expression of ICAM-1
      and E-selectin was assayed by flow cytometer. RESULT: l-THP(250 mg x L(-1))
      markedly attenuated ICAM-1 and E-selectin expression induced by LPS(P <0.05). l
      THP(50 mg x L(-1) inhibited E-selectin expression (P < 0.05) but had no effect on
      ICAM-1 (P > 0.05). l-THP (10 mg x L(-1)) had no effect on expression of both
      adhesion molecules. DXM (50 mg x L(-1)) completely inhibited both responses
      induced by LPS (P < 0.05). CONCLUSION: l-THP depresses expression of ICAM-1 and E
      selectin induced by LPS, which suggests that I-THP represent a promising
      candidate to be developed into therapies for the treatment of inflammation.

PMID- 16110874
TI  - The Cartagena Protocol on Biosafety: interaction between the Convention on
      Biological Diversity and the World Organisation for Animal Health.
AB  - The Cartagena Protocol on Biosafety is an international agreement (adopted on 29
      January 2000 as a supplementary agreement to the Convention on Biological
      Diversity) that addresses the potential adverse effects of living modified
      organisms. It focuses primarily on transboundary movements and is therefore
      relevant to international trade. It includes provisions on import decision
      making, risk assessment and management, information-sharing, documentation,
      capacity-building, compliance, liability and redress, public awareness and
      participation, and socio-economic considerations. Given the scope of the
      Protocol, there may be cases where trade in living modified organisms also falls
      under the mandate of existing international bodies such as the OIE (World
      Organisation for Animal Health) and other standard-setting bodies. There could
      therefore be benefits from collaboration between the Secretariat of the
      Convention on Biological Diversity and the World Organisation for Animal Health
      on issues such as risk assessment and management, information-sharing,
      documentation requirements, and procedures related to unintentional transboundary
      movements. This paper reviews the key provisions of the Protocol and attempts to
      highlight areas of the agreement which are also of interest to various
      international bodies, particularly the OIE.

PMID- 16110875
TI  - Genetics then and now: breeding the best and biotechnology.
AB  - In the past, domesticated animals were genetically improved by identifying
      meritorious individuals, mating animals displaying desired traits, continued
      breeding of related animals to perpetuate their superior traits and crossbreeding
      when inbreeding depression became evident. Today, assisted reproduction and
      biotechnology allow breeders to design and direct the reproductive course,
      disseminate desired traits and hasten genetic improvement. Generation interval
      can be greatly reduced by combining artificial insemination, which is the oldest
      and most widely used assisted reproductive technology, with the more recent
      techniques, such as oestrus synchronization, superovulation, ovum pick up from
      immature females even out of breeding season, and in vitro embryo production and
      transfer. Furthermore, the sex and genetic make-up of the offspring can be
      selected by using sex-sorted sperm for insemination, marker-assisted selection,
      functional deletion or addition of specific genes to the offspring's genome, or
      somatic cell nuclear transfer for cloning. However, the poor success rates with
      some of these procedures have delayed their large-scale application which, in
      turn, has hindered the proper evaluation of their genetic impact. The potential
      genetic consequences of some of these approaches merit the same degree of
      diligent evaluation that is currently extended to the procedures used for
      overcoming their 'technical' inefficiencies.

PMID- 16110876
TI  - A framework for the animal health risk analysis of biotechnology-derived animals:
      a Canadian perspective.
AB  - This paper describes the framework used by the Canadian Food Inspection Agency to
      assess the risks to animal health associated with biotechnology-derived animals
      and their products. In Canada the risks to animal health associated with
      biotechnology-derived animals are one consideration among several other
      regulatory concerns (e.g. human health, the environment). The risk analysis
      process begins with hazard identification, includes a risk assessment for each
      hazard, and concludes with risk management and risk communication.

PMID- 16110877
TI  - The safety assessment of foods from transgenic and cloned animals using the
      comparative approach.
AB  - The comparative approach to food safety assessment is based on the idea that the
      safety of a new food can largely be determined by its comparison to the benchmark
      of commonly consumed foods already in the food supply (also called the
      'conventional counterpart'). Any differences between the new food and its
      conventional counterpart are evaluated to determine their relevance to human
      health and safety. In this way it is possible to conclude whether a new food is
      'as safe as' conventional food already in the food supply. This approach, first
      developed primarily for use in the safety assessment of food from transgenic
      plants, is now generally accepted for food from both transgenic and cloned
      animals as well. This article outlines the basic principles behind the
      comparative approach, discusses some of the potential food safety concerns
      associated with transgenic and cloned animals, and describes important elements
      of the comparative approach and how these might be applied to assessing the
      safety of food from animals.

PMID- 16110878
TI  - Assessing ethics and animal welfare in animal biotechnology for farm production.
AB  - This paper addresses the ethical issues involved in animal biotechnology.
      Considerable advances in this field have been made with transgenic fish, which
      may be the first real test case for regulatory bodies. Intrinsic concerns about
      animal biotechnology are often voiced in public debate, and the paper presents
      and critically discusses these issues. Even though these concerns may be hard to
      reconcile with standards of rational argument, they might still have practical
      consequences for ethical policy making. Animal welfare and environmental issues
      are discussed as the most salient extrinsic concerns about animal biotechnology.
      The most serious obstacle to a good risk assessment of animal biotechnology is
      the extent of scientific uncertainty. Ethical assessments need to address these
      uncertainties upfront, and the precautionary principle provides a good criterion
      for responsible policies. At the end of the paper, a practical method for the
      ethical assessment of animal biotechnology, the so-called ethical matrix, is
      briefly presented and discussed.

PMID- 16110879
TI  - Biotechnology, animal health and animal welfare within the framework of European
      Union legislation.
AB  - Experimental and farm animals are used in biomedical research and in
      biotechnology studies that are designed to improve agricultural productivity.
      European legislation governing such research, which is modelled on existing
      National Laws regarding animal health and welfare, is agreed after several
      preliminary sessions in which contributions and opinions from large sections of
      European society are sought. Special attention is paid to opinions expressed by
      ethical and animal rights associations, which emphasise that animals should be
      considered as 'sentient beings' and not mere 'goods' or 'property'. A statement
      to this effect is included in the Treaty establishing a Constitution for Europe,
      which was signed in Rome in 2004 by the 25 European Union member states.

PMID- 16110880
TI  - Regulations governing veterinary medicinal products containing genetically
      modified organisms in the European community.
AB  - This paper describes particular aspects of the marketing of veterinary medicinal
      products (VMPs) that contain or consist of genetically modified micro-organisms
      (GMMs) or genetically modified organisms (GMOs). The regulatory requirements and
      the procedures applied in the European Union for each phase (pre-marketing,
      authorisation process, and post-authorisation labelling and monitoring) are
      explained. In most cases VMPs are subject to both pharmaceutical and GMO
      regulations. In the early stages of the process, before applications for
      marketing authorisation are submitted, the assessment of clinical trials and
      experiments in contained areas is principally the responsibility of national
      authorities. However, the marketing of all VMPs containing or consisting of GMOs
      must be authorised at European level, although the national authorities are
      informed and involved in the assessment process.

PMID- 16110881
TI  - Regulatory considerations in the development and application of biotechnology in
      Japan.
AB  - In Japan, the development and application of living modified organisms (LMOs) are
      regulated under the Law Concerning the Conservation and Sustainable Use of
      Biological Diversity. Procedures are classified as Type 1 for the use of LMOs
      where no preventive measures against their dispersal into the environment are
      required, and Type 2 for the use of LMOs with preventive measures. During the
      period of development, risk assessment is the responsibility of the Ministry of
      Education, Culture, Science, Sports and Technology. The procedures for field use
      of LMOs, including recombinant vaccines for veterinary use and genetically
      modified animals, are described in detail. Control systems for
      xenotransplantation of the cells, tissues and organs of transgenic pigs are yet
      to be established.

PMID- 16110882
TI  - Regulatory considerations for biotechnology-derived animals in Canada.
AB  - Regulatory initiatives relating to biotechnology-derived livestock have focused
      on animal health, environmental impact, and the general concept of the safety of
      the food and by-products derived from such animals. Existing regulatory
      frameworks have been stretched to accommodate these emerging concerns. Public
      concerns and the expectations of society mean that the regulatory infrastructure
      is subject to a high level of scrutiny and that regulations are expected to
      maintain a clear level of confidence, transparency and effectiveness. A sound
      regulatory regime should be 'neutral', neither 'facilitating' nor 'restricting'
      the approval of products or by-products derived from biotechnology-derived
      animals.

PMID- 16110883
TI  - Animal biotechnology: applications and economic implications in developing
      countries.
AB  - In most developing countries, biotechnological applications relating to livestock
      need to be suitable for animal owners who are resource-poor small-scale operators
      who own little or no land and few animals. Livestock is becoming increasingly
      important to economic growth in developing countries and the application of
      biotechnology is largely dictated by commercial considerations and socio-economic
      goals. Using technology to support livestock production is an integral part of
      viable agriculture in multi-enterprise systems. Livestock are part of a fragile
      ecosystem and a rich source of animal biodiversity, as local species and breeds
      possess genes and traits of excellence. Molecular markers are increasingly being
      used to identify and select the particular genes that lead to these desirable
      traits and it is now possible to select superior germ plasm and disseminate it
      using artificial insemination, embryo transfer and other assisted reproductive
      technologies. These technologies have been used in the genetic improvement of
      livestock, particularly in cattle and buffaloes, and the economic returns are
      significant. However, morbidity and mortality among animals produced using
      assisted reproductive technologies lead to high economic losses, so the principal
      application of animal biotechnology at present is in the production of cheap and
      dependable diagnostic kits and vaccines. Several obstacles limit the application
      of biotechnology at present: there is a lack of infrastructure and insufficient
      manpower, so funding is needed if resource-poor farmers are to benefit from
      biotechnology.

PMID- 16110884
TI  - Risk communication related to animal products derived from biotechnology.
AB  - Previous chapters of this review have dealt with the key considerations related
      to the application of biotechnology in veterinary science and animal production.
      This article explores the theory and practice of risk communication and sets out
      the basic principles for good risk communication when dealing with new
      technologies, uncertainty, and cautious and sceptical consumers. After failure to
      communicate with consumers and stakeholders about the risk to human health from
      bovine spongiform encephalopathy (BSE) in the 1990s, Government Agencies in the
      United Kingdom have made significant improvements in risk communication. The
      official inquiry that followed the BSE crisis concluded that a policy of openness
      was the correct approach, and this article emphasises the importance of
      consultation, consistency and transparency. There are, however, many different
      factors that affect public perception of risk (religious, political, social,
      cultural, etc.) and developing effective risk communication strategies must take
      all of these complex issues into consideration.

PMID- 16110885
TI  - Public perceptions of transgenic animals.
AB  - The field of animal biotechnology has been rapidly expanding and the development
      of transgenic animals has been part of this research expansion. How the public
      perceives such developments is an important component of policy considerations.
      In general, biotechnology applications have been judged with evident hierarchies
      of acceptability. There appearto be hierarchies in terms of the type of organism
      being modified, the purpose of the application, the means to attain particular
      ends, and the nature of the benefits obtained. While general awareness of
      biotechnology and its specific applications remains low to moderate, this article
      presents data regarding public acceptance of a variety of applications. These
      range from the use of animals as disease models and as sources for tissues and
      organs, to the use of transgenic animals for disease control, for food, and for
      the production of pharmaceutical and industrial products. Case-by-case judgments
      are evident, but at the same time, the application of criteria such as the nature
      of the organism being modified, the animal welfare aspects and the ethical-moral
      concerns are additional criteria for public judgments. These findings are
      discussed in the context of their implications for public policy.

PMID- 16110886
TI  - Novel vaccines from biotechnology.
AB  - Vaccination continues to be the main approach to protecting animals from
      infectious diseases. Until recently, all licensed vaccines were developed using
      conventional technologies. However, the introduction of modern molecular
      biological tools and genomics, combined with a better understanding of not only
      which antigens are critical in inducing protection, but an appreciation of host
      defences that must be stimulated, has opened a new opportunity to develop safer
      and more effective vaccines. The authors describe the current and future trends
      in vaccine development and stress that in addition to identifying and producing
      the protective antigens, it is critical to formulate and deliver these vaccines
      appropriately to maximise the potential of modern advances in pathogenesis and
      vaccinology.

PMID- 16110887
TI  - [Expression of foot and mouth disease virus antigens in transgenic plants].
AB  - Owing to its geographical distribution and its highly contagious character, the
      foot and mouth disease (FMD) virus is responsible for one of the most dreaded of
      all livestock diseases. The currently-used vaccine is polyvalent and is based on
      an inactivated virus. Current research on FMD vaccines focuses on the creation of
      vaccines that are easier and cheaper to produce, and that avoid manipulation of
      large quantities of virus. The use of transgenic plants to express relevant
      antigens has been evaluated for the purpose of vaccine production. The authors'
      working group has taken the FMD virus as a model to evaluate the feasibility of
      using transgenic plants to express viral antigens and to develop experimental
      vaccines. The purpose of this paper is to set forth the working group's results
      in the expression of FMD antigens in transgenic plants.

PMID- 16110888
TI  - Plant-based vaccines for animal health.
AB  - Plant-based vaccines are recombinant protein subunit vaccines. Ideally, the
      choice of plant species used to produce the selected antigen should allow for
      oral delivery in the form of an edible vaccine. These vaccines are well suited to
      combat diseases where there is a clear antigen candidate, and where the costs of
      production or delivery for any current vaccine are prohibitive. Several academic
      and industrial research groups are currently investigating the use of plant-based
      vaccines in both humans and animals. To date, the most advanced human vaccine
      projects have successfully completed phase I clinical trials, and animal vaccine
      projects have given promising data in early phase trials targeting specific
      animal species. In this article the advantages offered by plant-based vaccines
      will be presented, progress on the most advanced vaccine candidates will be
      summarised, and the path ahead will be outlined. Although the focus of this paper
      is on the application of plant-based vaccines in the field of animal health,
      principally their use in domestic livestock, examples of the use of plant-based
      vaccines in the field of human health will also be discussed.

PMID- 16110889
TI  - DNA vaccines for aquacultured fish.
AB  - Deoxyribonucleic acid (DNA) vaccination is based on the administration of the
      gene encoding the vaccine antigen, rather than the antigen itself. Subsequent
      expression of the antigen by cells in the vaccinated hosts triggers the host
      immune system. Among the many experimental DNA vaccines tested in various animal
      species as well as in humans, the vaccines against rhabdovirus diseases in fish
      have given some of the most promising results. A single intramuscular (IM)
      injection of microgram amounts of DNA induces rapid and long-lasting protection
      in farmed salmonids against economically important viruses such as infectious
      haematopoietic necrosis virus (IHNV) and viral haemorrhagic septicaemia virus
      (VHSV). DNA vaccines against other types of fish pathogens, however, have so far
      had limited success. The most efficient delivery route at present is IM
      injection, and suitable delivery strategies for mass vaccination of small fish
      have yet to be developed. In terms of safety, no adverse effects in the
      vaccinated fish have been observed to date. As DNA vaccination is a relatively
      new technology, various theoretical and long-term safety issues related to the
      environment and the consumer remain to be fully addressed, although inherently
      the risks should not be any greater than with the commercial fish vaccines that
      are currently used. Present classification systems lack clarity in distinguishing
      DNA-vaccinated animals from genetically modified organisms (GMOs), which could
      raise issues in terms of licensing and public acceptance of the technology. The
      potential benefits of DNA vaccines for farmed fish include improved animal
      welfare, reduced environmental impacts of aquaculture activities, increased food
      quality and quantity, and more sustainable production. Testing under commercial
      production conditions has recently been initiated in Canada and Denmark.

PMID- 16110890
TI  - [New vaccines and new veterinary therapies derived from biotechnologies: examples
      of applications].
AB  - The last ten years have seen the development of vaccines derived from
      deoxyribonucleic acid (DNA) recombination, which, when used in association with
      appropriate diagnostic kits, make it possible to distinguish vaccinated from
      infected animals. This article describes the general principles behind these
      vaccines, provides examples of different applications, e.g. vaccines against
      Aujeszky's disease, classical swine fever, rabies, avian diseases and rinderpest,
      and discusses the role of this type of vaccine in certain control plans.
      Deoxyribonucleic acid vaccines constitute a revolution in the concept of
      vaccination, which was previously based on the injection of a protein or a medium
      expressing a protein. It is now possible, however, to induce immunisation by
      direct injection of the gene that codes for the immunogenic antigen. Examples of
      such vaccines are described. Finally, the production of biological molecules used
      for therapeutic purposes thanks to genetic engineering techniques is illustrated
      by some examples concerning, in particular, animal bioreactors (transgenic
      animals).

PMID- 16110891
TI  - Traceability of biotech-derived animals: application of DNA technology.
AB  - Traceability is increasingly becoming standard across the agri-food industry,
      largely driven by recent food crises and the consequent demands for transparency
      within the food chain. This is leading to the development of a range of
      traceability concepts and technologies adapted to different industry needs.
      Experience with genetically modified plants has shown that traceability can play
      a role in increasing public confidence in biotechnology, and might similarly help
      allay concerns relating to the development of animal biotechnology. Traceability
      also forms an essential component of any risk management strategy and is a key
      requirement for post-marketing surveillance. Given the diversity of traceability
      concepts and technologies available, consideration needs to be given to the scope
      and precision of traceability systems for animal biotechnology. Experience to
      date has shown that conventional tagging and labelling systems can incorporate
      levels of error and may not have sufficient precision for biotech-derived
      animals. Deoxyribonucleic acid (DNA) technology can overcome these difficulties
      by tracing animals and animal by-products through their DNA code rather than an
      associated label. This offers the possibility of tracing some by-products of
      animal biotechnology through the supply chain back to source animals, offering
      unprecedented levels of traceability. Developments in both DNA sampling and
      analysis technology are making large-scale applications of DNA traceability
      increasingly cost effective and feasible, and are likely to lead to a broader
      uptake of DNA traceability concepts.

PMID- 16110892
TI  - Diagnostic tools for animal diseases.
AB  - While traditional testing methods are still widely used in veterinary diagnostic
      laboratories exciting new technologies, such as biosensors and microarray
      techniques, are being developed. Nucleic acid diagnostic techniques such as
      polymerase chain reaction (PCR) have become routine diagnostic tools in
      veterinary laboratories not only to make specific typing determinations but also
      to rapidly screen large numbers of samples during disease outbreaks. In addition,
      nanotechnologies, although not yet implemented in veterinary laboratories, hold
      the promise of screening for numerous pathogens in a single assay. Other
      biotechnologies are likely to be widely used in the future as they can improve
      diagnostic capabilities while reducing the time and perhaps, the costs,
      associated with conventional technologies. This paper describes some of these new
      technologies and concludes that although a lot of developmental work is still
      required, biotechnology and its applications hold great promise for improving the
      speed and accuracy of diagnostics for veterinary pathogens.

PMID- 16110893
TI  - Animal cloning: problems and prospects.
AB  - An efficient animal cloning technology would provide many new opportunities for
      livestock agriculture, human medicine, and animal conservation. Nuclear cloning
      involves the production of animals that are genetically identical to the donor
      cells used in a technique known as nuclear transfer (NT). However, at present it
      is an inefficient process: in cattle, only around 6% of the embryos transferred
      to the reproductive tracts of recipient cows result in healthy, longterm
      surviving clones. Of concern are the high losses throughout gestation, during
      birth and in the post-natal period through to adulthood. Many of the pregnancy
      losses relate to failure of the placenta to develop and function correctly.
      Placental dysfunction may also have an adverse influence on postnatal health.
      These anomalies are probably due to incorrect epigenetic reprogramming of the
      donor genome following NT, leading to inappropriate patterns of gene expression
      during the development of clones. Whilst some physiological tests on surviving
      clones suggest normality, other reports indicate a variety of post-natal clone
      associated abnormalities. This variability in outcome may reflect species
      specific and/or cloning methodological differences. Importantly, to date it
      appears that these clone-associated phenotypes are not transmitted to offspring
      following sexual reproduction. This indicates that they represent epigenetic
      errors, rather than genetic errors, which are corrected during gametogenesis.
      Whilst this needs confirmation at the molecular level, it provides initial
      confidence in the first application of NT in agriculture, namely, the production
      of small numbers of cloned sires from genetically elite bulls, for natural
      mating, to effectively disseminate genetic gain. In addition to the animal
      welfare concerns with the technology, the underlying health of the animals and
      the consequential effect on food safety are critical aspects that require
      investigation to gain regulatory and consumer acceptance. Future improvements in
      animal cloning will largely arise from a greater understanding of the molecular
      mechanisms of reprogramming.

PMID- 16110894
TI  - [Confinement and consumption of cloned and transgenic animals].
AB  - Reproduction by cloning can eliminate some of the problems inherent to sexual
      reproduction, but it creates others. The genetic heritage of nucleus donor cells
      and the genetic status of clones are not precisely known. Furthermore,
      reprogramming of the genome of nucleus donor cells by the ovocyte cytoplasm is
      often incomplete. Animals obtained through cloning are thus essentially
      genetically identical to their genitors, but they are often epigenetically
      modified, with unpredictable effects. Transgenesis results in most cases from the
      addition to a genome of one or more known genes. The direct and indirect effects
      of transgenesis cannot all be predicted. Specific confinement measures make it
      possible to raise animals in high-security conditions, preventing their
      dissemination in the human food chain, in animal feed or in the environment. The
      toxicity, allergenicity and infectiousness of cloned ortransgenic animals can be
      evaluated by means of tests.

PMID- 16110895
TI  - Disease-resistant genetically modified animals.
AB  - Infectious disease adversely affects livestock production and animal welfare, and
      has impacts upon both human health and public perception of livestock production.
      The authors argue that the combination of new methodology that enables the
      efficient production of genetically-modified (GM) animals with exciting new tools
      to alter gene activity makes the applications of transgenic animals for the
      benefit of animal (and human health) increasingly likely. This is illustrated
      through descriptions of specific examples. This technology is likely to have
      specific application where genetic variation does not exist in a given population
      or species and where novel genetic improvements can be engineered. These
      engineered animals would provide valuable models with which to investigate
      disease progression and evaluate this approach to controlling the disease. The
      authors propose that the use of GM animals will complement the more traditional
      tactics to combat disease, and will provide novel intervention strategies that
      are not possible through the established approaches.

PMID- 16110896
TI  - Transgenic farm animals: present and future.
AB  - Until recently, pronuclear microinjection of deoxyribonucleic acid (DNA) was the
      standard method for producing transgenic animals. This technique is now being
      replaced by more efficient protocols based on somatic nucleartransferthat also
      permit targeted genetic modifications. Lentiviral vectors and small interfering
      ribonucleic acid technology are also becoming important tools for transgenesis.
      Transgenic farm animals are important in human medicine as sources of
      biologically active proteins, as donors in xenotransplantation, and for research
      in cell and gene therapy. Typical agricultural applications include improved
      carcass composition, lactational performance and wool production, as well as
      enhanced disease resistance and reduced environmental impact. Product safety can
      be ensured by standardisation of procedures and monitored by polymerase chain
      reaction and array technology. As sequence information and genomic maps of farm
      animals are refined, it becomes increasingly practical to remove or modify
      individual genes. This approach to animal breeding will be instrumental in
      meeting global challenges in agricultural production in the future.

PMID- 16110897
TI  - Developments in transgenic fish in the People's Republic of China.
AB  - In the People's Republic of China, genetically modified (GM) fish are being
      developed primarily to produce desirable alterations to growth rates or feed
      conversion efficiency. Up to the present, no transgenic fish have been
      commercially approved for human consumption. This review introduces advances in
      the People's Republic of China in transgenic fish studies, biosafety studies of
      fast-growth GM fish, and the regulation of GM fish.

PMID- 16110898
TI  - Current scientific understanding of the environmental biosafety of transgenic
      fish and shellfish.
AB  - A fluorescent zebrafish was the first genetically engineered animal to be
      marketed, and biotechnologists are developing many transgenic fish and shellfish.
      Biosafety science is not sufficiently advanced to be able to draw scientifically
      reliable and broadly trusted conclusions about the environmental effects of these
      animals. The science is best developed for identifying hazards posed by
      environmental spread of a transgenic fish or shellfish and least developed for
      assessing potential ecological harms of spread. Environmental spread of certain
      transgenic fish or shellfish could be an indirect route of entry into the human
      food supply. The management of predicted environmental risks is in its infancy
      and has thus far focused on the first step of the risk management process, i.e.
      risk reduction, via a few confinement methods. There is a critical need to
      improve scientific methods of environmental safety assessment and management and
      to gather empirical data needed to substantiate biosafety conclusions and to
      effectively manage transgenic fish and shellfish. Scientists and potentially
      affected parties should participate in prioritising the knowledge gaps to be
      addressed.

PMID- 16110899
TI  - The potential hazards of xenotransplantation: an overview.
AB  - Xenotransplantation, in particular the transplantation of pig cells, tissues and
      organs into human recipients, may alleviate the current shortage of suitable
      allografts available for human transplantation. This overview addresses the
      physiological, immunological and microbial factors involved in
      xenotransplantation. The issues reviewed include the merits of using pigs as
      xenograft source species, the compatibility of pig and human organ physiology,
      and the rejection mechanism and attempts to overcome this immunological
      challenge. The authors discuss advances in the prevention of pig organ rejection
      through the creation of genetically modified pigs, more suited to the human micro
      environment. Finally, in regard to microbial hazards, the authors review possible
      viral infections originating from pigs.

PMID- 16110900
TI  - The ethics debate in relation to xenotransplantation.
AB  - Xenotransplantation is the transplantation of organs and cells from one species
      to another: it has enormous potential to increase the supply of organs and
      tissues to alleviate human disease. Recent scientific progress has eliminated the
      obstacle of hyperacute rejection, which is the massive destruction of the
      transplanted organ within 24 h. Despite this progress and the tremendous clinical
      potential, a number of ethical issues require careful consideration. These issues
      involve the human recipients, source animals, biotechnology companies and
      ultimately, the general public. One of the greatest concerns is the potential
      risk that an infectious agent will be transferred with the organ to the
      recipient, from whom it may spread, leading to a possible epidemic. However,
      there is no current evidence that porcine endogenous retrovirus, which is the
      agent of greatest concern, will be pathogenic. Using modern biotechnology, it may
      be possible to generate pigs that are free of this virus in the near future.
      Addressing these issues deliberately and in a scientific manner, with public
      involvement and education, will result in a greater understanding of the risks
      and benefits of xenotransplantation. This knowledge can then be utilised to
      fulfil the increasing demand for transplantable organs, with minimal risk.

PMID- 16110901
TI  - Use of molecular markers to enhance resistance of livestock to disease: a global
      approach.
AB  - The improvement and utilisation of host genetic resistance to disease is an
      attractive option as a component of livestock disease control in a wide range of
      situations. This paper reviews the situations where genetic resistance of the
      host is likely to be a useful component of disease control and provides a
      framework for deciding whether genetic improvement of resistance is likely to be
      worthwhile. Discussion is focused on low-input production systems in the
      developing world, where disease resistance is particularly important. The authors
      propose an integrated strategy for the use of molecular markers in assessing
      genetic diversity and in utilising and improving host genetic resistance to
      disease. The integrated approach assures that there is value in the molecular
      genetic information whether or not it proves useful in genetic selection, a
      feature that should prove attractive to funding and executing agencies.

PMID- 16110902
TI  - Functional genomics: tools for improving farm animal health and welfare.
AB  - The first genome sequence assemblies of farm animal species are now accessible
      through public domain databases, and further sequencing projects are in rapid
      progress. In addition, large collections of expressed sequences have been
      obtained, which will aid in constructing annotated transcript maps for many
      economically important species. Thus, the breeding of farm animals is entering
      the post-genome era. Functional genomics, defined as applying global experimental
      approaches to assess gene function, by using the information and reagents
      provided by structural genomics (i.e. mapping and sequencing), has become the
      focus of interest. Combining a holistic view of phenotypes at the molecular level
      with genetic marker data seems a particularly promising approach for improving
      health and welfare traits in farm animals. These traits are often difficult to
      define. They suffer from low heritabilities and a corresponding lack of genetic
      gain in conventional selection and breeding programmes. At the same time, genomic
      information from micro-organisms and parasites offers the potential for new
      vaccines and therapeutics. This review describes major functional genomics tools,
      lists genomic resources available for farm animals and discusses the prospects
      and challenges of functional genomics in improving the health and welfare of farm
      animals.

PMID- 16110903
TI  - The use of marker-assisted selection in animal breeding and biotechnology.
AB  - Improvement of livestock has focused on the selective breeding of individuals
      with superior phenotypes. With the development of increasingly advanced
      statistical methods that maximise selection for genetic gain, this simple
      approach has been extremely successful in increasing the quantity of agricultural
      output. However, information now available on the organisation and functioning of
      the genome could be used in breeding programmes to improve a range of traits.
      Many traits are under the control of several genetic loci, each of which
      contribute to the variation in the trait and hence are called quantitative trait
      loci (QTL). While genetic markers for QTL that are linked to the trait gene could
      be used to choose animals for selective breeding programmes, the most effective
      markers are the functional mutations within the trait genes. Strategies to
      identify markers for traits and the application of these markers are described by
      reference to examples of loci that control a range of different traits.

PMID- 16110904
TI  - Assisted reproductive technologies in cattle: a review.
AB  - Over a period of approximately thirty years, commercial bovine embryo transfer
      has become a large international business. The technology is well established,
      and more than 500,000 embryos are produced annually from superovulated cows world
      wide. Since bovine embryos with intact zonae pellucidae can be specified pathogen
      free through washing procedures, thousands of frozen embryos are routinely sold
      and transferred between countries. Throughout the world, approximately 15% of
      bovine embryos are produced by in vitro technology. Polymerase chain reaction
      technology is currently being used for sexing embryos on a small scale, and it is
      likely that this technology will be used for 'embryo diagnostics' in the future.
      Semen sexing is an established technology and is likely to be used on a small
      scale in the near future, especially in in vitro embryo production systems. The
      cloning of adult cattle through nuclear transfer and the production of cloned,
      transgenic cattle has been technically achieved. However, this is an expensive
      and inefficient technology, which is being used primarily by the pharmaceutical
      industry. Benefits in agriculture are likely to be minimal in the near future.

PMID- 16110905
TI  - Embryo technology: implications for fertility in cattle.
AB  - During the past thirty years, basic and experimental studies on classical
      (superovulation; non-surgical recovery and transfer of cattle embryos) and
      advanced embryo technologies (in vitro embryo production; cloning by somatic cell
      nuclear transfer) have generated structural and functional information on oocyte
      development and quality, fertilisation and conceptus development. This
      information has provided new insight, not only into these technologies per se but
      also into the factors contributing to fertility in cattle. It is now known that
      the peripheral and follicular endocrine profiles have a profound influence on the
      subsequent developmental competence of the embryo. It is also well established
      that manipulation of the oocytes or embryos may adversely affect embryonic and
      foetal development, leading to the so-called 'large offspring syndrome'.
      Information from such studies has alerted scientists to the importance of
      epigenetics in cattle reproduction.

PMID- 16110906
TI  - Cellular and molecular mechanisms regulating oocyte quality and the relevance for
      farm animal reproductive efficiency.
AB  - The efficiency of breeding schemes is dependent on the high fecundity of the
      selected individuals. Reproductive technologies are constantly pushing the
      physiological limits, but while the male reproductive potential is almost fully
      exploited, female reproductive physiology is the subject of constant research.
      Since the number of offspring that a female can bring to term each pregnancy
      cannot be changed, the ideal approach is to remove the potential offspring at the
      beginning of development and to transfer them to recipients of lesser genetic
      value. The earlier the collection takes place, the higher the number of
      descendants that a female can generate, so that now, the number of available
      oocytes becomes the limiting factor. This article will describe how detailed
      studies on oocyte physiology are beginning to unravel the complex sequence that
      transforms a small primordial follicle into a large ovulatory follicle containing
      a mature oocyte. Progressively, the limits to oocyte manipulation have been
      recognised and gradually overcome with adequate hormonal treatments in vivo and
      with specific media supplementation in vitro. This has led to the development of
      highly efficient reproductive technologies and the promise of even greater
      advances in the future. Surprising new findings, such as ovarian stem cells that
      can replenish the follicle population or long term embryonic stem cell lines that
      can differentiate into oocytes, are rapidly changing our expectations.

PMID- 16110907
TI  - Nanotechnology and animal health.
AB  - Nanotechnology, as a new enabling technology, has the potential to revolutionise
      agriculture and food systems in the United States of America and throughout the
      world. Examples of potential applications of nanotechnology in the science and
      engineering of agriculture and food systems include disease treatment delivery
      systems, new tools for molecular and cellular biology, the security of
      agricultural and food systems, new materials for pathogen detection, and
      protection of the environment. Existing research has clearly demonstrated the
      feasibility of introducing nanoshells and nanotubes into animal systems to seek
      out and destroy targeted cells. Nanoparticles smaller than one micron have been
      used to deliver drugs and genes into cells. Thus, some building blocks do exist
      in isolation and are expected to be integrated into systems over the next 10 to
      15 years. It is reasonable to presume over the next couple of decades that
      nanobiotechnology industries and unique developments will revolutionise animal
      health and medicine.

PMID- 16110908
TI  - Drawing conclusions: the future of the animal health and biotechnology
      partnership.

PMID- 16110909
TI  - Antimicrobial activity of some substituted triazoloquinazolines.
AB  - Fifteen substituted 1,2,4-triazolo[4,3-c]quinazolines were tested for
      antibacterial and antifungal effects. The most effective derivatives had the
      triazoloquinazoline skeleton substituted with the pharmacologically active
      chromophores--morpholine, chlorine and nitro group. The broadest antimicrobial
      activity was found with 5-morpholin-4-yl-3-(5-nitrothien-2-yl)[1,2,4]triazolo[4,3
      c]quinazoline in concentration of 10 mg/L for B. subtilis, 50 mg/L for S. aureus
      and 100 mg/L for C. tropicalis. The highest tested concentration of derivative
      caused 83% growth inhibition of R. nigricans.

PMID- 16110910
TI  - Hemolytic uremic syndrome caused by verotoxin-producing Escherichia coli O26.
      Case report.
AB  - Verotoxin-producing Escherichia coli (VTEC) are nowadays among the most important
      emerging group of food-borne pathogens (VTEC strains cause gastroenteritis that
      can be complicated by the hemorrhagic colitis or hemolytic uremic syndrome, HUS).
      Escherichia coli 026 producing verotoxin 2 was isolated and its identity
      confirmed by examination of phenotype and genotype; the strain was first
      described in Slovakia in association with the development of HUS in a 4-year-old
      girl.

PMID- 16110911
TI  - Effect of pH on production of virulence factors by biofilm cells of Pseudomonas
      aeruginosa.
AB  - Effect of pH on production of extracellular virulence factors of Pseudomonas
      aeruginosa grown on catheter in biofilm was determined. Alginate and proteinase
      production was higher at pH 8; in contrast, siderophores (pyochelin and
      pyoverdin) were synthesized more intensively at pH 5.

PMID- 16110912
TI  - Detection and recovery of hydrolytic enzymes from spent compost of four mushroom
      species.
AB  - To evaluate the potential of using the enzymes from spent mushroom compost (SMC)
      as an industrial enzyme, the production of alpha-amylase, cellulase, beta
      glucosidase, laccase, and xylanase was determined from the SMC of four edible
      mushroom species (Pleurotus ostreatus, Lentinula edodes, Flammulina velutipes and
      Hericium erinaceum). Among the tested SMC, the SMC of L. edodes showed the
      highest enzyme activity in alpha-amylase (229 nkat/g), cellulase (759 nkat/g) and
      beta-glucosidase (767 nkat/g) in 0.5% Triton X-100, and that of P. ostreatus
      showed the highest activity in laccase (1452 nkat/g) in phosphate-buffered 0.2%
      Triton X-100. The highest xylanase activity (119 nkat/g) was found in the SMC of
      F. velutipes.

PMID- 16110913
TI  - PCR assay for detection and differentiation of K88ab(1), K88ab(2), K88ac, and
      K88ad fimbrial adhesins in E. coli strains isolated from diarrheic piglets.
AB  - Primers were designed and prepared and conditions were determined for PCR
      detection and differentiation of enterotoxigenic E. coli bacterial strains
      isolated from diarrheic pigs. Primers K88/1 and K88/2 are 25 bp oligomers that
      correspond to a region of genes encoding one of serological variants of the K88
      antigen (K88ab(1), K88ab(2), K88ac or K88ad). A positive result of PCR is an
      amplificate of 792 bp in size for K88ab and K88ad variant or 786 bp for K88ac
      variant. The individual serological variants of genes of the K88 antigen could be
      differentiated by cutting the obtained PCR amplificates by restriction
      endonucleases. The PCR analysis of 674 E. coli strains isolated from diarrheic
      pigs showed that 184 strains were K88 positive. By using restriction
      endonucleases the K88-positive strains were in 4 cases classified as K88ab
      variant, 180 as K88ac variant and none contained gene for the K88ad variant.
      Ninety-five % coincidence with serological examination using K88ab, K88ac and
      K88ad specific antibodies was shown.

PMID- 16110914
TI  - Production of catalases by Comamonas spp. and resistance to oxidative stress.
AB  - Bacterial isolates Comamonas terrigena N3H (from soil contaminated with crude
      oil) and C. testosteroni (isolated from the sludge of a wastewater treatment
      plant), exhibit much higher total catalase activity than the same species from
      laboratory collection cultures. Electrophoretic resolution of catalases revealed
      only one corresponding band in cell-free extracts of both C. testosteroni
      cultures. Isolates of C. terrigena N3H exhibited catalase-1 and catalase-2
      activity, whereas in the collection culture C. terrigena ATCC 8461 only catalase
      1 was detected. The environmental isolates exhibited much higher resistance to
      exogenous H2O2 (20, 40 mmol/L) than collection cultures, mainly in the middle and
      late exponential growth phases. The stepwise H2O2-adapted culture of C. terrigena
      N3H, which was more resistant to oxidative stress than the original isolate,
      exhibited an increase of catalase and peroxidase activity represented by catalase
      1. Pretreatment of cells with 0.5 mmol/L H2O2 followed by an application of the
      oxidative agent in toxic concentrations (up to 40 mmol/L) increased the rate of
      cell survival in the original isolate, but not in the H2O2-adapted variant. The
      protection of bacteria caused by such pretreatment corresponded with stimulation
      of catalase activity in pretreated culture.

PMID- 16110915
TI  - Extended-spectrum beta-lactamase-conferring transferable resistance to different
      antimicrobial agents in Enterobacteriaceae isolated from bloodstream infections.
AB  - Twenty (18.5%) out of 108 clinical isolates of the family Enterobacteriaceae
      responsible for bloodstream infection were extended-spectrum beta-lactamase
      (ESBL)-positive in two screening tests, the double disk synergy test and the
      Oxoid Combination Disk method. Eleven out of the 20 ESBL-positive isolates
      transferred oxyimino-beta-lactam resistance to E. coli K12 C600 recipient strain
      with a frequency of 10(-8) - 10(-1) per donor cell. PCR analysis revealed that
      the majority of the transconjugants (9 of 11) express CTX-M-type beta-lactamases.
      Donor strains and their transconjugants displayed susceptibility patterns typical
      of ESBL producers. They were resistant to oxyimino-beta-lactams but susceptible
      to clavulanic acid and carbapenems. Resistances to aminoglycosides, tetracycline
      and mercuric chloride were, in some cases, co-transferred with oxyimino-beta
      lactam resistance, suggesting that various resistance determinants were carried
      by the same conjugative plasmids.

PMID- 16110916
TI  - Evaluation of histological techniques for the detection of fungal infections
      caused by Leptolegnia chapmanii (Oomycetes: Saprolegniales) in Aedes aegypti
      (Diptera: Culicidae) larvae.
AB  - We evaluated which of the fixatives and stains most frequently used for
      observation of insect tissues were the most appropriate for histopathological
      visualization of entomopathogenic fungal infections with Leptolegnia chapmanii in
      larvae of Aedes aegypti. The best contrast between the host tissues and the
      fungal structures was obtained when using a combination of Camoy fixative with
      Grocott staining contrasted with light green. Masson trichromic stain combined
      with 10% formaldehyde-phosphate buffer also provided satisfactory results--a good
      contrast and clearly distinguishable host tissues and fungal structures.

PMID- 16110917
TI  - Nonspecific elicitation of defense reaction in suspension tobacco cells by
      elicitors from Armillaria.
AB  - Ergosterol and chitin oligomers were detected in water extracts from Armillaria
      gallica, A. cepistipes, A. tabescens, A. ostoyae and A. mellea containing as
      active components elicitors able to trigger early events of defense reaction in
      suspension tobacco cells. More virulent strains of A. ostoyae and A. mellea had
      the same ability of elicitation as weak pathogens A. gallica, A. cepistipes, A.
      tabescens. The elicitation of the defense reaction early events by chitin
      oligomers was markedly enhanced by ergosterol probably due to the activation of
      several signal pathways.

PMID- 16110918
TI  - Constitutive alpha-amylase producing mutant and recombinant haploid strains of
      thermophilic fungus Thermomyces lanuginosus.
AB  - Morphological, developmental and antimetabolite-resistant mutants of T.
      lanuginosus were characterized and used for screening with the aim to develop
      constitutive alpha-amylase-hyperproducing strains. The protoplast fusion of two
      spontaneous mutants of T. lanuginosus, characterized as asporulating and
      resistant to 2-deoxy-D-glucose (2DG), resulted in sporulating, 2DG sensitive
      heterokaryotic fusants. A recombinant haploid strain F64fB developed there from
      produced alpha-amylase constitutively in glucose-containing medium. Constitutive
      alpha-amylase-hyperproducing mutant (III8) obtained after cyclic mutagenesis and
      screening yielded approximately 20 fold more alpha-amylase in a glycerol
      containing medium than the wild strain.

PMID- 16110919
TI  - Points of commitment to reproductive events as a tool for analysis of the cell
      cycle in synchronous cultures of algae.
AB  - Methods for determining the points of commitment for cell division are described
      for species of green algae dividing by multiple fission, both forming coenobia
      (Scenedesmus quadricauda) and releasing single daughter cells (Chlamydomonas
      eugametos, Scenedesmus armatus). The timing of commitment points was followed in
      detail in synchronous cultures of S. quadricauda grown under various light
      intensities, illumination regimes, and temperatures. The pre-commitment periods
      were rate limiting, while the post-commitment periods remained more or less
      constant under various light intensity. Temperature, on the other hand, affected
      both periods in a similar manner and they were prolonged with decreasing
      temperature.

PMID- 16110920
TI  - Application of PCR, rep-PCR and RAPD techniques for typing of Lactococcus lactis
      strains.
AB  - A collection of 34 lactococcal strains were characterized using the polymerase
      chain reaction (PCR) for the acmA gene, and for the 16S rDNA gene, and DNA
      fingerprinting methods for randomly amplified polymorphic DNA (RAPD) and
      repetitive extragenic palindrome-PCR (rep-PCR). PCR experiments corroborated the
      genotypic identification of Lactococcus lactis strains by RAPD; rep-PCR did not
      distinguish between L. lactis subspecies. In some cases, phenotypic
      classification of L. lactis subspecies did not correlate with genotypic
      characterization.

PMID- 16110921
TI  - Ligninolytic ability and potential biotechnology applications of the South
      American fungus Pleurotus laciniatocrenatus.
AB  - The extracellular ligninolytic enzyme system of Pleurotus laciniatocrenatus,
      grown under different culture conditions, was characterized and the ability of
      this strain to degrade different components of Eucalyptus globulus wood was
      determined. In shaken liquid cultures grown on a C-limited medium supplemented
      with yeast extract (0.1%) and peptone (0.5%), the fungus produced extracellular
      aryl-alcohol oxidase (Aao), laccase (Lac), manganese-dependent peroxidase (MnP)
      and manganese-independent peroxidase (MiP) activities, their maximum levels
      being, respectively, about 600, 50, 1360, and 920 pkat/mL. The supplementation of
      1 mmol/L vanillic acid and 150 micromol/L CuSO4 produced an increase of Lac
      activity levels up to 4-fold and 68.3-fold, respectively. No significant
      differences were found in the levels of the other ligninolytic enzyme activities
      when compared to the basal medium. Solid-state fermentation cultures on E.
      globulus wood chips revealed Lac and MiP activities. These cultures showed
      degradative activity on lignin and lipophilic wood extractives.

PMID- 16110922
TI  - Physiology and microbial community structure in soil at extreme water content.
AB  - A sandy loam soil was brought to 6 water contents (13-100% WHC) to study the
      effects of extreme soil moistures on the physiological status of microbiota
      (represented by biomass characteristics, specific respiration, bacterial growth,
      and phospholipid fatty acid, PLFA, stress indicators) and microbial community
      structure (assessed using PLFA fingerprints). In dry soils, microbial biomass and
      activity declined as a consequence of water and/or nutrient deficiency (indicated
      by PLFA stress indicators). These microbial communities were dominated by G+
      bacteria and actinomycetes. Oxygen deficits in water-saturated soils did not
      eliminate microbial activity but the enormous accumulation of poly-3
      hydroxybutyrate by bacteria showed the unbalanced growth in excess carbon
      conditions. High soil water content favored G bacteria.

PMID- 16110923
TI  - Antibiotic-induced release of inflammatory mediators from bacteria in
      experimental Klebsiella pneumoniae-induced sepsis.
AB  - In a fibrin-clot model of sepsis, developed in mice, treatment with the
      antibiotics ceftazidime (Cfz) and ofloxacin (Ofl) caused significant (p < 0.01)
      release of endotoxin and TNF-alpha after 4.5 h when compared with control
      (untreated) and amikacin (Ami) treated group. Except for control group, the level
      of bacteremia declined in all three antibiotic-treated groups. The results
      suggest that antibiotic therapy, irrespective of the agent used, results in an
      increase in endotoxin levels in vivo. The amount of endotoxin liberated by Ami
      was much smaller than with Cfz and Ofl therapy, which makes it an appropriate
      agent for the treatment of sepsis. An increase in the level of TNF-alpha along
      with endotoxin is suggestive of increased inflammatory response.

PMID- 16110924
TI  - Analysis of recombinant group B streptococcal protein ScaAB and evaluation of its
      immunogenicity.
AB  - Group B streptococcal (GBS) gene encoding the putative lipoprotein and adherence
      factor ScaAB was cloned and expressed in E. coli. Recombinant ScaAB protein was
      isolated. Signal sequence of ScaAB was found to be cleaved in the E. coli host.
      ScaAB recombinant protein was immunogenic in mice and antibodies against this
      protein were discovered in mice sera after GBS infection. The perspectives of the
      use of ScaAB protein in GBS vaccine are discussed.

PMID- 16110925
TI  - WHOQOL-BREF as predictors of mortality: a two-year follow-up study at veteran
      homes.
AB  - The main purpose of this study was to evaluate the effectiveness of the brief
      version of the World Health Organization Quality of Life (WHOQOL-BREF)
      questionnaire as a predictor of mortality amongst the elderly. A total of 689
      male residents of veteran homes, all above the age of 65 years, were randomly
      selected in 2001. The Taiwan version of the WHOQOL-BREF was administered as the
      baseline, with each of these subjects being interviewed and subsequently followed
      up for mortality until the end of 2003. Data on self-reported global health, life
      satisfaction, medical status, physical performance and health behavior was also
      collected. Following the death of 105 of the 689 subjects during the 2-year
      follow-up period, the relative risk (RR) of death was subsequently assessed using
      Cox's proportional hazard regression analyses. After adjusting for other
      predictors (age group, chronic diseases, emergency visits, hospitalization,
      physical performance, regular exercise, self-reported global health and life
      satisfaction), almost all of the WHOQOL-BREF items and domains failed to predict
      mortality; the one exception was working capacity levels (score 1-2 vs. score 4
      5) which, after adjusting for other predictors, did demonstrate the ability to
      predict mortality (RR = 1.96, p < 0.05).

PMID- 16110926
TI  - Relationships between health domains and sense of coherence: a two-year cross
      lagged study in patients with chronic illness.
AB  - The latent structure of Sense of Coherence (SOC) and its relationship with three
      domains of health (body function, activity and participation) were studied in a
      cohort of people with chronic illness (n = 771) over a period of 2 years. A
      structural equation approach with cross-lagged and synchronous models was applied
      to each combination of SOC and domain of health. Over the 2-year period SOC had
      enhanced body function and participation. Conversely, levels of activities as
      well as body function had contributed to SOC 2 years later. Significant
      synchronous effects were found that indicated the presence of reciprocal
      causation between SOC and all three domains of health. These findings challenge
      existing SOC theory and suggest that SOC can be considered a relevant outcome
      variable in chronic illness care.

PMID- 16110927
TI  - Population-based study of the relationship of treatment and sociodemographics on
      quality of life for early stage breast cancer.
AB  - OBJECTIVE: To examine the relationship between cancer stage, surgical treatment
      and chemotherapy on quality of life (QOL) after breast cancer and determine if
      sociodemographic characteristics modify the observed relationships. METHODS: A
      population-based sample of women with Stages 0-II breast cancer in the United
      States (N = 1357) completed surveys including the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30),
      and the Breast Cancer-Specific Quality of Life Questionnaire (QLQ BR-23).
      Regression models calculated mean QOL scores across primary surgical treatment
      and chemotherapy. Clinically significant differences in QOL were defined as > or
      = 10 point difference (out of 100) between groups. RESULTS: Meaningful
      differences in QOL by surgical treatment were limited to body image with women
      receiving mastectomy with reconstruction reporting lower scores than women
      receiving breast conserving surgery (p < 0.001). Chemotherapy lowered QOL scores
      overall across four QOL dimensions (p values < 0.001), with a disproportionately
      greater impact on those with lower levels of education. Younger women reported
      lower QOL scores for seven of nine QOL dimensions (p values < 0.001).
      CONCLUSIONS: Women should be reassured that few QOL differences exist based on
      surgical treatment, however, clinicians should recognize that the impact of
      treatment on QOL does vary by a woman's age and educational level.

PMID- 16110928
TI  - Perceived cognitive function in coronary artery disease--an unrecognised
      predictor of unemployment.
AB  - OBJECTIVE: We aimed to assess whether perceived cognitive function influences
      employment and return to work in patients with coronary artery disease (CAD).
      DESIGN: Prospective longitudinal cohort study. SETTING: Health care system of
      Sodertalje, Stockholm County, Sweden. PATIENTS: We included consecutive
      unselected patients less than 65 years of age with CAD and followed them during 2
      years. MAIN OUTCOME MEASURES: Gainful employment and return to work in patients
      with CAD. RESULTS: We found that perceived cognitive function predicts both
      prevalence of unemployment [OR 2.06 (95% CI: 1.36-3.13); p = 0.0006] and early
      retirement and sick leave due to coronary artery disease [OR 1.59 (95% CI: 1.12
      2.25)] both at baseline and 2 years later. Furthermore, perceived cognitive
      function predicted return to work after an acute coronary event [OR 2.28 (95% CI:
      1.08-4.84)]. Covariates such as age, sex, prevalence and degree of angina (CCS
      grade), cardiovascular risk factors and events did not change the predictive
      power. CONCLUSIONS: Perceived cognitive function is a hitherto unrecognised
      independent predictor of unemployment, sick leave and return to work in patients
      with coronary artery disease. Perceived cognitive function adds a new perspective
      on ability to gainful employment in patients with CAD. The findings might have
      significance both to individual care and to society.

PMID- 16110929
TI  - Understanding the complex associations between patient-provider relationships,
      self-care behaviours, and health-related quality of life in type 2 diabetes: a
      structural equation modeling approach.
AB  - OBJECTIVES: To assess associations between perceptions of the patient-provider
      relationship (PPR), BMI, and adherence to diet and exercise in a rural population
      with type 2 diabetes and determine how these variables relate to HRQL. METHODS: A
      model of the hypothesized relationships between the constructs was proposed and
      tested using structural equation modeling (SEM) and data collected as part of a
      controlled study to improve care for individuals with type 2 diabetes in rural
      health regions. RESULTS: In the final model, positive perceptions of the PPR had
      a direct impact on adherence to diet (beta = 0.23; p < 0.05), exercise (beta =
      0.13; p < 0.05) and diabetes management attitudes (beta = 0.33; p < 0.05). The
      direct path from management attitudes to exercise was also significant (beta =
      0.12; p < 0.05). Direct predictors of HRQL included management attitudes (beta =
      0.16; p < 0.05), exercise adherence (beta = 0.14, p < 0.05) and BMI (beta = 
      0.23; p < 0.05). Exercise adherence predicted BMI, whereas adherence to diet did
      not. The final model had an acceptable fit with the measured data (chi2 = 30.6
      (26, N = 372), p = 0.25; RMSEA = 0.02; TLI = 0.98; SRMR = 0.02). CONCLUSION:
      Patient-provider relationship and exercise adherence appeared to be key
      constructs in the model. HRQL in people with type 2 diabetes was positively
      associated with exercise adherence, which was related to a positive PPR.
      Adherence to diet was also related to a positive PPR, but diet adherence had no
      association with HRQL.

PMID- 16110930
TI  - Diabetes-related symptoms and negative mood in participants of a targeted
      population-screening program for type 2 diabetes: The Hoorn Screening Study.
AB  - OBJECTIVE: To determine the level of diabetes-related symptom distress and its
      association with negative mood in subjects participating in a targeted population
      screening program, comparing those identified as having type 2 diabetes vs. those
      who did not. RESEARCH DESIGN AND METHODS: This study was conducted within the
      framework of a targeted screening project for type 2 diabetes in a general Dutch
      population (age 50-75 years). The study sample consisted of 246 subjects, pre
      selected on the basis of a high-risk profile; 116 of whom were subsequently
      identified as having type 2 diabetes, and 130 who were non-diabetic subjects.
      Diabetes-related symptom distress and negative mood was assessed approximately 2
      weeks, 6 months, and 12 months after the diagnosis of type 2 diabetes, with the
      Type 2 Diabetes Symptom Checklist and the Negative well-being sub scale of the
      Well-being Questionnaire (W-BQ12), respectively. RESULTS: Screening-detected
      diabetic patients reported significantly greater burden of hyperglycemic (F =
      6.0, df = 1, p = 0.015) and of fatigue (F = 5.3, df = 1, p = 0.023) symptoms in
      the first year following diagnosis type 2 diabetes compared to non-diabetic
      subjects. These outcomes did not change over time. The total symptom distress
      (range 0-4) was relatively low for both screening-detected diabetic patients
      (median at approximately 2 weeks, 6 months, and 12 months; 0.24, 0.24, 0.29) and
      non-diabetic subjects (0.15, 0.15, 0.18), and not significantly different. No
      average difference and change over time in negative well-being was found between
      screening-detected diabetic patients and non-diabetic subjects. Negative well
      being was significantly positive related with the total symptom distress score
      (regression coefficient beta = 2.86, 95% CI 2.15-3.58). CONCLUSIONS: The
      screening-detected diabetic patients were bothered more by symptoms of
      hyperglycemia and fatigue in the first year following diagnosis type 2 diabetes
      than non-diabetic subjects. More symptom distress is associated with increased
      negative mood in both screening-detected diabetic patients and non-diabetic
      subjects.

PMID- 16110931
TI  - Quality of life and eating disorders.
AB  - OBJECTIVE: Eating disorders (EDs) can have a serious impact on various life
      domains and may lead to physical, mental and social impairment and consequently
      to poor quality of life (QOL). This study compared the QOL of ED patients and
      former ED patients in a large community based sample to the QOL of a normal
      reference group and to the QOL of patients with mood disorders. Differences
      between ED diagnostic groups were examined. The study investigated what factors
      contribute to QOL. METHODS: A generic health-related quality of life
      questionnaire, the Short Form-36 (SF-36), and the Eating Disorder Examination
      Questionnaire were administered to 156 ED patients--44 anorexia nervosa patients,
      43 bulimia nervosa patients, 69 eating disorder not otherwise specified patients-
      and 148 former ED patients. RESULTS: ED patients reported significantly poorer
      QOL than a normal reference group. No differences were found between the
      diagnostic groups. Former ED patients still had poorer QOL than a normal
      reference group. ED patients reported significantly poorer QOL than patients with
      mood disorders. Self esteem contributed most to QOL. CONCLUSION: EDs have a
      severe impact on many domains of QOL. Therefore QOL needs to be addressed in
      effectiveness research and clinical practice.

PMID- 16110932
TI  - Comparison of the minimally important difference for two health state utility
      measures: EQ-5D and SF-6D.
AB  - BACKGROUND: The SF-6D and EQ-5D are both preference-based measures of health.
      Empirical work is required to determine what the smallest change is in utility
      scores that can be regarded as important and whether this change in utility value
      is constant across measures and conditions. OBJECTIVES: To use distribution and
      anchor-based methods to determine and compare the minimally important difference
      (MID) for the SF-6D and EQ-5D for various datasets. METHODS: The SF-6D is scored
      on a 0.29-1.00 scale and the EQ-5D on a -0.59-1.00 scale, with a score of 1.00 on
      both, indicating 'full health'. Patients were followed for a period of time, then
      asked, using question 2 of the SF-36 as our anchor, if their general health is
      much better (5), somewhat better (4), stayed the same (3), somewhat worse (2) or
      much worse (1) compared to the last time they were assessed. We considered
      patients whose global rating score was 4 or 2 as having experienced some change
      equivalent to the MID. This paper describes and compares the MID and standardised
      response mean (SRM) for the SF-6D and EQ-5D from eight longitudinal studies in 11
      patient groups that used both instruments. RESULTS: From the 11 reviewed studies,
      the MID for the SF-6D ranged from 0.011 to 0.097, mean 0.041. The corresponding
      SRMs ranged from 0.12 to 0.87, mean 0.39 and were mainly in the 'small to
      moderate' range using Cohen's criteria, supporting the MID results. The mean MID
      for the EQ-5D was 0.074 (range -0.011-0.140) and the SRMs ranged from -0.05 to
      0.43, mean 0.24. The mean MID for the EQ-SD was almost double that of the mean
      MID for the SF-6D. CONCLUSIONS: There is evidence that the MID for these two
      utility measures are not equal and differ in absolute values. The EQ-5D scale has
      approximately twice the range of the SF-6D scale. Therefore, the estimates of the
      MID for each scale appear to be proportionally equivalent in the context of the
      range of utility scores for each scale. Further empirical work is required to see
      whether or not this holds true for other utility measures, patient groups and
      populations.

PMID- 16110933
TI  - Analysis of incomplete quality of life data in advanced stage cancer: a practical
      application of multiple imputation.
AB  - This paper presents a practical approach to analyzing incomplete quality of life
      (QOL) data that contains non-ignorable dropouts in patients with advanced non
      small-cell lung cancer (NSCLC). QOL scores for the physical domain at baseline
      and at the end of the first and second courses of chemotherapy were compared
      between two treatment groups in a phase III trial. One hundred and 103 eligible
      patients were randomized to receive cisplatin and irinotecan (CPT-P) or cisplatin
      and vindesine, respectively; of those two groups, 83 and 85, respectively,
      completed a QOL questionnaire at least at baseline. A multiple imputation
      incorporating auxiliary QOL variables was implemented as one of alternatives of
      sensitivity analyses; these were complete case, available case, and pattern
      mixture analyses. Although larger sensitivity to missing data was found for CPT-P
      treatment, none of the alternative analyses demonstrated a significant difference
      in estimated slopes over time between the groups. This study presents an
      analytical approach for dealing with the complex problem of missing QOL data. It
      must be noted, however, that the validity of the multiple imputation method we
      present is not certain unless we can specify sufficiently informative auxiliary
      variables to ensure the conversion of non-ignorable missingness to ignorable.

PMID- 16110934
TI  - Quantifying responsiveness of quality of life measures without an external
      criterion.
AB  - The responsiveness of a quality of life measure has received considerable
      attention in the literature. A two time-point (pre-/post-) study design is
      usually adopted to evaluate this property when a gold standard is not available.
      Among many indices, Cohen's effect size and the standardized response mean (SRM)
      are usually computed. To interpret the results, researchers commonly appeal to an
      arbitrary criterion for both indices even though they are different by
      definition. In this paper, we demonstrate their close algebraic relationship and
      conceptual differences, showing that only the SRM is necessary to quantify
      responsiveness. To facilitate interpretation, we transform the SRM to the
      'probability of change' with a value of 0.5 denoting null responsiveness and 1.0
      perfect responsiveness. Simple confidence interval procedures are provided and
      evaluated. We also discuss the possibility of applying the results to the
      analysis of data from a two independent groups pre-/post- design. Two examples
      are provided.

PMID- 16110935
TI  - Developing a questionnaire to measure the psychosocial impact of an abnormal
      cervical smear result and its subsequent management: the TOMBOLA (Trial of
      Management of Borderline and Other Low-grade Abnormal Smears) trial.
AB  - This paper describes the process of developing and testing a new questionnaire,
      Process Outcome Specific Measure (POSM), including an assessment of its content
      validity and reliability. The questionnaire was developed within the context of
      Trial Of Management of Borderline and Other Low-grade Abnormal smears (TOMBOLA)
      to assess the psychosocial impact of a low-grade abnormal cervical smear result
      and the subsequent management. A literature search, focus groups and thorough pre
      testing involving experts and patients resulted in a short (15-item), easily
      completed and understood questionnaire. Questions address issues including
      cancer, health, fertility and sexual concerns. Repeatability was assessed in 110
      TOMBOLA recruits using weighted k; all but one of the questions showed levels of
      reliability near to, or above, 0.5. Cronbach's standardised alpha was 0.73,
      indicating acceptable internal consistency. Each POSM item was correlated with
      the anxiety and depression sub-scales of the Hospital Anxiety Depression Scale
      (HADS). All except one of the questions correlated more highly with the total
      POSM score than with the HADS sub-scales thus indicating discriminant validity.
      The POSM will enable comparison of the alternative management policies for low
      grade cervical smears in terms of the benefits (or otherwise) perceived by the
      women managed by these policies.

PMID- 16110936
TI  - Academic and behavioral limitations and health-related quality of life in school
      age survivors of bacterial meningitis.
AB  - The objectives of this study were to describe health-related quality of life of
      postmeningitic children and to examine the association between academic and/or
      behavioral limitations and health-related quality of life. One hundred and eighty
      two children (mean age 9.7 years; range 5.3-14.2) were selected randomly from a
      cohort of 674 school-age children who recovered from non-Haemophilus influenzae
      type B bacterial meningitis. These children had neither meningitis with 'complex
      onset', nor prior cognitive or behavioral problems, nor severe disease sequelae.
      On average 7.4 years after meningitis, they were evaluated using an 'Academic
      Achievement Test' and their parents filled in the Child Behavior Checklist, the
      Child Health Questionnaire, and the Health Utilities Index. The long-term
      incidence of academic and/or behavioral limitations was 32%. Overall health
      related quality of life of the postmeningitic children was decreased in
      comparison with that of a reference population of schoolchildren. The group of
      postmeningitic children with academic and/or behavioral limitations showed the
      most marked decrease in quality of life, especially concerning psychosocial
      health, cognition and family life. The negative effects on quality of life were
      not significantly influenced by age, gender, causative pathogen, presence of
      minor neurological impairment, or presence of hearing impairment. In conclusion,
      health-related quality of life of postmeningitic children is decreased,
      particularly of those with academic and/or behavioral limitations.

PMID- 16110937
TI  - Adolescent health-related quality of life and perceived satisfaction with life.
AB  - PURPOSE: To explore the relationship between perceived satisfaction with life and
      health-related quality of life (HRQOL) in a state-wide sample of 13-18-year-old
      adolescents (n = 4914) in South Carolina, USA. METHODS: Questions were added to
      the self-report Centers for Disease Control (CDC) Youth Risk Behavior Survey
      (YRBS) asking about perceived life satisfaction in six domains (self, family,
      friends, living environment, school, and overall) and HRQOL (self-rated health;
      and the number of poor physical health days, poor mental days, and activity
      limitation days during the past 30 days). RESULTS: Adjusted logistic regression
      analyses and multivariate models constructed separately revealed that self-rated
      health, poor physical days (past 30 days), poor mental health days (past 30
      days), and activity limitation days (past 30 days) were significantly related (p
      < 0.05) to reduced life satisfaction, regardless of race or gender. Moreover, as
      the number of reported poor health days increased, the greater the odds of
      reporting life dissatisfaction. CONCLUSIONS: This is the first study to document
      the relationship between poor physical health and perceived life satisfaction.
      This adds to the mounting evidence that life satisfaction is related to a variety
      of adolescent health behaviors and that life satisfaction may add additional
      information in longitudinal databases that track adolescent health because it
      appears to be related to HRQOL.

PMID- 16110938
TI  - The relationship between health-related quality of life, pain, and coping
      strategies in juvenile arthritis--a one year prospective study.
AB  - The aim of this 12-month prospective study was to compare reports describing the
      health-related quality of life (HRQL) of children with Juvenile idiopathic
      arthritis (JIA) obtained from parents and children, to investigate the extent to
      which the children's HRQL changed over a 12-month period, and to describe the
      relationship between children's HRQL, and their experience of pain and use of
      pain coping strategies. Fifty-four children aged 8-18 years with JIA and their
      parents completed standard questionnaires assessing children's HRQL, pain
      intensity, and pain coping strategies at baseline, 6 months, and 12 months. In
      general, children reported that their HRQL was better than was reported by
      parents. Both informants described children's HRQL as being very stable over the
      12 months of the study. Consistent with the Biobehavioural Model of Pain, there
      was a significant negative relationship between children's HRQL and their
      experience of pain. However, there was little evidence that pain coping
      strategies mediated the relationship between children's experience of pain and
      their HRQL.

PMID- 16110939
TI  - Determinants of quality of life in children with psychiatric disorders.
AB  - OBJECTIVE: To assess factors that, in addition to childhood psychopathology, are
      associated with Quality of Life (QoL) in children with psychiatric problems.
      METHODS: In a referred sample of 252 8 to 18-year-olds, information concerning
      QoL, psychopathology and a broad range of child, parent, and family/ social
      network factors was obtained from children, parents, teachers and clinicians.
      RESULTS: Poor child, parent, and clinician reported QoL was associated with child
      psychopathology, but given the presence of psychopathology, also with child
      factors, such as low self-esteem, and poor social skills, and family/social
      network factors, such as poor family functioning, and poor social support. In
      multiple linear regression analyses the importance of parent factors, such as
      parenting stress, was almost negligible. CONCLUSION: To increase QoL of children
      with psychiatric problems, treatment of symptoms is important, but outcome might
      improve if treatment is also focussed on other factors that may affect QoL.
      Results are discussed in relation to current treatment programs.

PMID- 16110940
TI  - Preliminary psychometric evaluation of the Child Health Ratings Inventory (CHRIs)
      and Disease-Specific Impairment Inventory-Hematopoietic Stem Cell Transplantation
      (DSII-HSCT) in parents and children.
AB  - PURPOSE: To describe the initial results of the Child Health Ratings Inventory
      (CHRIs), 20-item generic health-related quality of life (HRQL) instrument and the
      10-item disease-specific (DS) module, the Disease Specific Impairment Inventory
      Hematopoietic Stem Cell Transplantation (DSII-HSCT), for children and
      adolescents, ages 5-18 years and their parents following HSCT. STUDY DESIGN:
      Using cross sectional design, 122 children with a median age of 11 years (range
      5.0-18 years) completed the questionnaire (CHRIs + DSII-HSCT) with research
      assistance. Seventy-four parents independently completed a parallel version of
      the questionnaire; health care providers assigned a global clinical severity
      rating. RESULTS: The generic core includes four domains: physical, role, and
      emotional functioning, and energy. The DS module has three domains: worry,
      hassles, and body image. The Cronbach's alpha for parents and for older children
      (8 years and over) exceeded 0.70 for all generic and DS domains. While the range
      of alpha coefficients was lower for younger children, ages 5-7 year, only the
      alpha coefficient for one domain (energy) was less than 0.70. The instrument
      satisfactorily discriminated between clinically important groups: those early in
      the transplant process (< 6 months) versus those later (> 12 months) and by
      provider-assigned clinical severity ratings. CONCLUSION: results suggest that the
      CHRIs generic core and its DSII-HSCT module is a promising measure of HRQL after
      pediatric HSCT. Although parent and child reports were moderately correlated and
      revealed complementary results, the unique perspectives of both raters provide a
      more complete picture of HRQL. Longitudinal application is underway to further
      characterize the measurement properties of the CHRIs and to determine the
      instrument's responsiveness and sensitivity to change over time in this
      vulnerable population.

PMID- 16110941
TI  - Korean translation and validation of the functional assessment of cancer therapy
      breast (FACT-B) scale version 4.
AB  - We undertook to translate and cross-culturally adapt the Functional Assessment of
      Cancer Therapy-Breast (FACT-B) scale into Korean and to evaluate its reliability
      and validity. The translation procedure followed the standard Functional
      Assessment of Chronic Illness Therapy translation methodology. A total of 201
      breast cancer patients (mean age, 43.87 years) were studied for psychometric
      properties of the FACT-B scale. A pre-test of 20 Korean breast cancer patients
      indicated that the Korean FACT-B scale provided good content coverage and overall
      comprehensibility. Our results indicated high internal consistency of the FACT-B
      scale, with Cronbach's alpha coefficients ranging from 0.79 to 0.90. The only
      exception was the Breast Cancer Scale (BCS), which had a Cronbach's alpha
      coefficient of 0.67. We can consider that most of the patients in this study had
      not resumed sexual activity after surgery and found it difficult to comment on
      this aspect. We also considered that contents of the BCS may have been somewhat
      heterogeneous. After performing a factor analysis of the BCS data from this
      study, we identified three factors, accounting 58.8%: psychological distress (5
      items, with explained variances of 27.5%), feminine satisfaction (2 items, with
      explained variances of 17.1%), and physical complaints (2 items, with explained
      variances of 14.2%). The FACT-B scale also demonstrated good convergent and
      divergent validity when correlated with the shortened forms of the Profile of
      Mood States and the Functional Living Index-Cancer (FLIC). We can now evaluate
      the Quality of Life (QoL) of Korean breast cancer patients using this reliable
      and valid instrument. Nevertheless our study has the limitation that it did not
      evaluate the sensitivity to the changes of the patients' QoL in the long term
      follow-up, and we will supplement it in our further study.

PMID- 16110942
TI  - Development and psychometric tests of the Chinese-version Low Vision Quality of
      Life Questionnaire.
AB  - BACKGROUND/AIMS: To develop and assess the psychometric validity of a Chinese
      language Vision Health related quality-of-life (VRQoL) measurement instrument for
      the Chinese visually impaired. METHODS: The Low Vision Quality of Life
      Questionnaire (LVQOL) was translated and adapted into the Chinese-version Low
      Vision Quality of Life Questionnaire (CLVQOL). The CLVQOL was completed by 100
      randomly selected people with low vision (primary group) and 100 people with
      normal vision (control group). Ninety-four participants from the primary group
      completed the CLVQOL a second time 2 weeks later (test-retest group). The
      internal consistency reliability, test-retest reliability, item-internal
      consistency, item-discrimination validity, construct validity and discriminatory
      power of the CLVQOL were calculated. RESULTS: The review committee agreed that
      the CLVQOL replicated the meaning of the LVQOL and was sensitive to cultural
      differences. The Cronbach's alpha coefficient and the split-half coefficient for
      the four scales and total CLVQOL scales were 0.75-0.97. The test-retest
      reliability as estimated by the intraclass correlations coefficient was 0.69
      0.95. Item-internal consistency was > 0.4 and item-discrimination validity was
      generally < 0.40. The Varimax rotation factor analysis of the CLVQOL identified
      four principal factors. the quality-of-life rating of four subscales and the
      total score of the CLVQOL of the primary group were lower than those of the
      Control group, both in hospital-based subjects and community-based subjects.
      CONCLUSION: The CLVQOL Chinese is a culturally specific vision-related quality-of
      life measure instrument. It satisfies conventional psychometric criteria,
      discriminates visually healthy populations from low vision patients and may be
      valuable in screening the local community as well as for use in clinical practice
      or research.

PMID- 16110943
TI  - Assessment of quality of life among HIV-infected persons in Pune, India.
AB  - OBJECTIVE: To study dimensions of Quality of Life (QOL) amongst HIV infected
      persons, their relationship with socio-demographic characteristics and disease
      progression. DESIGN: Cross-sectional study with one time assessment of QOL.
      METHODS: Modified Medical Outcome Study (MOS) core instrument [The Medical
      Outcome Study 116 core set of Measures of functioning and well being, Appendix A,
      core survey instrument (internet)] was interview--administered to 100 HIV
      infected individuals. RESULTS: The instrument showed significant positive inter
      domain correlations and desired linear association between QOL scores and the CD4
      counts. The scale had a Cronbach alpha value of 0.75. QOL was markedly affected
      in the domains of physical health, work and earnings, routine activities and
      appetite and food intake. Women had significantly lower QOL scores than men
      despite having less advanced disease. The QOL scores were significantly lower
      among persons with lower CD4 counts mainly in different domains of physical
      health. CONCLUSIONS: The modified MOS scale had the desired reliability and
      validity for evaluation of QOL in the HIV-infected persons in India. Low scores
      in the domains of physical health compared to other domains suggest a strategy to
      focus on medical intervention. A need for psychosocial intervention for women was
      perceived. Longitudinal studies must be done to assess the impact of anti
      retroviral therapy being rolled out through the national programme on QOL.

PMID- 16110944
TI  - [Study on the animal model for severe acute respiratory syndrome].
AB  - To screen small animals susceptible to SARS-CoV, five species of animals,
      including guinea pig, hamster, albino hamster, chicken and rat, were
      experimentally infected with SARS-CoV strain BJ-01 by different routes. On the
      basis of this, further cynomolgus and rhesus macaques were selected and
      experimentally inoculated SARS-CoV, the quality they serve as animal model for
      SARS was evaluated. The results showed that, all five species of small animals
      chosed were not susceptible to SARS-CoV, no characterized changes in clinical
      sign and histopathology were observed after infection, but from the lung samples
      of large rat and pig guinea, the genomic RNA of SARS-CoV could be detected by RT
      PCR at day 14 post infection, this suggested that SARS-CoV could replicate in
      these animals. After inoculated with SARS-CoV, all inoculated cynomolgus and
      rhesus macaques had developed interstitial pneumonia of differing severity. These
      changes on histopathology were similar to that seen in SARS patients, but the
      pathological lesions were less severe than that of human. Except interstitial
      pneumonia, no other characterized pathological changes were observed. This
      suggested cynomolgus and rhesus macaques were not the ideal animal model for SARS
      in fact, but they could serve as animal model for SARS when a more ideal animal
      model is absent.

PMID- 16110945
TI  - [Demonstration of simultaneous infection with dengue type 2 and 3 in a Chinese
      patient].
AB  - IgG and IgM antibodies to dengue virus(DEN) in patient serum sample were detected
      with an indirect immunofluorescence assay. The patient's serum was inoculated
      into the culture of C6/36 cells to isolate dengue virus. Viral RNA was extracted
      from cultured supernatant and RT-PCR amplification and sequencing were carried
      out. The result showed that there were anti-dengue virus IgG and IgM antibodies
      in the serum. Both dengue type 2 and 3 virus specific sequences were confirmed by
      RT-PCR and sequence analysis. The results presented here demonstrated the
      simultaneous infection with dengue type 2 and 3 viruses in the Chinese patient.

PMID- 16110946
TI  - [Amphibacillus haojiensis sp. nov.--a novel alkaliphilic and slight halophilic
      bacterium from Haoji Soda Lake in Inner Mongolia Autonomous Region, China].
AB  - An alkaliphilic and slightly halophilic Gram-positive rod, designated strain F10,
      was isolated from Haoji soda lake in Inner Mongolia Autonomous Region, China.
      Strain F10 grew optimally in the presence of 3% (W/V) NaCl, pH 9.5 and 37 degrees
      C. It was facultatively anaerobic, motile with peritrichous flagella,
      sporulating, catalase- negative. The (G + C) content of the DNA was 40 mol%. The
      cell wall contained meso-DAP. Phylogenetic analyses based on 16S rDNA sequences
      comparisons indicate that strain F10 was a member of the genus Amphibacillus. DNA
      DNA similarity of less than 30% with the described species of Amphibacillus
      supported the view that this organism represented a new species of the genus
      Amphibacillus. The name Amphibacillus haojiensis sp. nov. is proposed.

PMID- 16110947
TI  - [Isolation and characterization of new species hydrogen producing bacterium
      Ethanologenbacterium sp. strain X-1 and its capability of hydrogen production].
AB  - To obtain hydrogen-producing bacterium of high efficiency, a strain X-1 of
      hydrogen-producing bacteria was isolated from the continuous stirred-tank reactor
      (CSTR) by anaerobic Hungate technique. The Comparative sequence analysis of 16S
      rDNA showed that homology of strain X-1 with Clostridium cellulose and
      Acetanaerobacterium elongatum is less than 94%. All sequence alignment of 16S-23S
      rDNA intergenic spacer regions (ISR) indicated displayed that consensus region is
      tRNA(Ala), and tRNA(Ile), variable region is not homologous. Morphological,
      physic-biochemical character, and comparative sequence analysis of 16S rDNA and
      16S-23S rDNA ISR indicated that strain X-1 belong to new genus named
      Ethanologenbacterium gen. nov.. Strain X-1 is facultative anaerobe bacillus; its
      main fermentative products are acetic acid, ethanol, H2 and CO2. The metabolic
      character of strain X-1 is typical ethanol type fermentation. Its capability of
      hydrogen production was measured in the batch culture experiment. X-1's maximum
      specific hydrogen producing rate is 28.3 mmol H2/( g dry cell x h) at pH 4.0 and
      36 degrees C. Result of identify and analysis of hydrogen production ability
      demonstrated strain X-1 belong to new genus of high hydrogen-producing bacteria.

PMID- 16110948
TI  - [A Sinorhizoboium meliloti strain that can nodulate soybean plants].
AB  - Sinorhizobium meliloti XJ96077 was isolated from root nodules of alfalfa
      (Medicago sativa) in Xinjiang Region of China. Nodulation experiments showed that
      both soybean and alfalfa were effectively nodulated by XJ96077. The DNA (G+ C)
      mol% of strain XJ96077 was 61.9%. The DNA homologies of strain XJ96077 were 93%
      and 80% with S. meliloti USDA1002T and 042BM, respectively. These results showed
      that XJ96077 belongs to Sinorhizobium meliloti. To prove the capability of
      XJ96077 to nodulate both soybean and alfalfa, constitutively expressed green
      fluorescence protein gene gfp was introduced to XJ96077, and the recombinant
      strain XJ96077(G) was obtained. Root nodules of the soybean and alfalfa
      inoculated with XJ96077(G) and the expression of gfp were observed using the
      confocal laser scanning microscope. XJ96077 showed various nodulation capacities
      with different soybean cultivars.

PMID- 16110949
TI  - [Study on actinomycetes population of alpine meadow soil in Qinghai].
AB  - Soil samples were collected from six kinds of soil in Haibei alpine meadow
      ecosystem during 2001 - 2002. More than 300 strains of actinomycete were isolated
      by five agar media. On the basis of morphological characteristics and some
      chemotaxonomic properties, the isolated strains were classified into different
      genera, such as Micromonospora, Nocardia, Saccharopolyspora, Promicromonospora,
      Streptomyces, and the Streptomyces strains were classified into seven groups. The
      result indicated that the biodiversity of actinomycetes in different soils and
      the actinomycetes abundance of different kinds showed significant differences.
      The activities of some enzymes produced by mesophilic and psychrophilic
      actinomycetes also discussed in this paper. It is found that many strains of
      streptomyces not only have some enzyme activities such as starch decomposition,
      nitrate deoxidization, gelatin utilization etc., but also have some inhibiting
      activities for fungi and bacteria offered to test, whereas the rare actinomyces
      showed low positive rate of enzyme activities and inhibiting activities for fungi
      and bacteria.

PMID- 16110950
TI  - [Purification and structural analysis of the nucleocapsid of PRRS virus expressed
      from Escherichia coli].
AB  - The DNA fragment encoding the nucleocapsid protein (N) of PRRSV BJ4 strain were
      cloned into the BamH I / EcoR I sites of pET28a vector to construct the
      expression plasmid pET28-N by designing special primers. The soluble protein (P28
      N) were obtained by introducing the expression plasmid into E. coli BL21 (DE3)
      host cell, and the amount of recombinant protein reached to 28% of the total mass
      of bacterial protein. PET28-N were purified by nickel-affinity column of Proband
      resin. The circular dichroism (CD) analysis showed that the purified PET28-N
      shared a significant (26%) alpha-helical structure, beta-sheet (23.7%), beta-turn
      (19.8%), and random coil (30.3%), respectively. Finally,the secondary structure
      of N protein of PRRSV was deduced.

PMID- 16110951
TI  - [Histopathological research and immunofluorescence of AVND virus infection in
      cultured scallop Chlamys farreri].
AB  - The naturally infected scallops Chlamys farreri sampled during mass mortality in
      summer of 2003 was detected by means of histopathological and MAb-based
      immunofluorescence assay (IFA). The results of histological examination
      demonstrated that a series of histopathological changes including cell swelling,
      basophilic increase, disorder, partial sloughing and excessive sloughing were
      always observed in epithelia of many different organs, e.g. mantle, gills,
      stomach, intestine and kidney. Additionally, the infected tissues were applied
      for in situ detection of the "acute virus necrobiotic disease" (AVND) virus by
      means of specific MAb-based IFA, and the result demonstrated that this
      pathological changes or lesions were perfectly coincident with the positive cells
      (fluorescencing cells) . The positive cells were denser in some local area of
      epithelia, and exhibited serious pathological lesions, which would reveal the
      roles of this virus in pathogenesis and further confirm that the AVND virus is
      the main causative agent of mass mortalities among cultured scallop Chlamys
      farreri farmed in northern coast of China.

PMID- 16110952
TI  - [Prokaryotic expression and immuno-localization of replication protein gene of
      Tobacco curly shoot virus].
AB  - The replication protein (Rep) gene of Tobacco curly shoot virus (TbCSV) Y35
      isolate was obtained from the infected tobacco plants by PCR and cloned into
      expression vector pGEX-4T-1 to generate the recombinant plasmid pGEX-Y35Rep. The
      recombinant plasmid was introduced into Escherichia coli strain BL21(DE3) pLys S,
      and TbCSV Rep fusion protein was expressed with induction by IPTG and some
      products were soluble. The Rep fusion protein was purified with GST-Sepharose 4B
      affinity chromatography and its polyclonal antibody was produced in a rabbit.
      Studies on subcellular distribution of TbCSV Rep protein in infected tobacco
      leaves revealed that Rep protein mainly exists in the fractions containing the
      nucleus. Immuno-gold labeling with the antibody against Rep fusion protein also
      indicated that Rep protein localized in the nuclei of infected tobacco cells.

PMID- 16110953
TI  - [Expression and characterization of the recombination anthrax lethal factor].
AB  - The gene encoding anthrax lehtal factor (LF) was cloned into a secretory
      expression plasmid and then expressed in periplasmic space of E. coli. The
      recombinant LF (rLF) expressed was about 4% of the total proteins in E. coli.
      About 3 mg electrophoresis purity rLF could be obtained after the purification of
      1 liter culure using ion exchange chromatography and gel filtration. The result
      of sequencing assay showed that the N-terminal amino acid sequence of rLF was
      identical to the N-terminal sequence of natural LF. In vitro toxicity analysis
      also shows that rLF has an excellent biological activity. The successful
      expression of rLF has placed a solid foundation for the research on toxicity
      mechanism of LF, developing new anthrax vaccines, and screening for inhibitors
      against anthrax toxin.

PMID- 16110954
TI  - [Prokaryotic expression and bioactivity of the Listeria monocytogenes
      listeriolysin O].
AB  - To express the Listeria monocytogenes hly gene in Escherichia coli and study its
      primary biological characteristics, hly gene without signal peptide sequence was
      amplified from Listeria monocytogenes serotype 4b by PCR and inserted into T-easy
      vector. Sequencing showed this hly gene was 1518 bp and nucleotide homology was
      more than 99.8% compared with three Listeria monocytogenes hly genes in GenBank.
      The cloned hly gene was then inserted into prokaryotic expression vector pGEX-6P
      1 and transformed into E. coli BL21. The predicted fusion protein was detected by
      SDS-PAGE after IPTG inducion, which had molecular weight approximately 82 kD.
      Hemolytic experiment demonstrated the expressed fusion protein can lyse human red
      cell and its hemolytic titer attained 2.26 x 10(4) HU/mg. Conclusively, the
      Listeria monocytogenes hly gene was successfully cloned and expressed in E. coli.
      The successful expression of LLO in E. coli BL21 constituted a solid foundation
      for further researches such as pathogenesis and immune mechanism, MAb and vaccine
      development.

PMID- 16110955
TI  - [Sequence of Escherichia coli O138 O-antigen gene cluster and gne identification
      by bioinformatics].
AB  - E. coli O138 is one of the enterotoxigenic Escherichia coli, causing the
      postweaning diarrhea and edema disease of weaned pigs. The O-antigen gene cluster
      of E. coli O138 was sequenced and found to contain the genes rmlB-DAC and gne,
      gna for the biosynthesis of nucleotide sugars dTDP-rhamnose and UDP-GalNAcA,
      respectively, genes encoding for O unit flippase(wzx), O-antigen polymerase(wzy)
      and 3 potential transferase genes. The possible biosynthesis pathway for rare UDP
      GalNAcA was proposed. Two genes specific to E. coli O138 were identified. This
      work provides the basis for a sensitive test by PCR for the rapid detection of E.
      coli O138. Phylogenetic tree for Gne and GalE proteins was generated and
      comparisons were made among different strains, and results revealed that these
      proteins are similar in the second structure, and Gne of E. coli O138 was
      identified by bioinformatics.

PMID- 16110957
TI  - [Construction and functional analysis of the pepB gene disruptant in Aspergillus
      niger].
AB  - An integration plasmid pMW1-pepB for the pepB gene disruption in Aspergillus was
      constructed. The plasmid contained the pepB gene upstream (P) 1.4kb and
      downstream (T) 1.3kb homologous fragments with insertion of the expression unit
      of the hygromycin resistance gene (hph) between them. P and T DNA fragments were
      synthesized by PCR from Aspergillus niger chromosomal DNA. The integration
      plasmid was digested with the Hpa I restriction enzyme, the resultant 4.2kb
      linear fragment was introduced into the Aspergillus niger strain GICC2773 which
      expressing the glucoamylase/laccase fusion protein by PEG-mediated
      transformation. 62 Hygromycin resistance transformants were screened, and from
      them one strain named pepB29 was identified to be the pepB disruptant by PCR
      analysis. Data of functional assay of the pepB29 strain indicated that the
      disruption of the pepB gene secreted reduced acid proteolytic activity, and
      improved the heterologous protein laccase production.

PMID- 16110956
TI  - [Differential regulation of phenazine-1-carboxylic acid and pyoluteorin
      production mediated by inactivated gacA in Pseudomonas sp. M18].
AB  - Pseudomonas sp. M18 is one of the plant-growth-promoting rhizobacteria, which can
      produce fungicides: phenazine-1-carboxylic acid (PCA) and pyoluteorin (Plt). The
      chromosomally gacA inactivated mutant named M18G was constructed and its PCA
      production was enhanced 31-fold and Plt production was almost blocked completely
      in KMB medium. To assess the mutual influence of two antibiotics, the plt gene
      cluster mutant M18T and the phz gene cluster mutant M18GA were then constructed.
      Non-Plt-producing M18T could synthesize the same amount of PCA as wild type
      strain. Plt could not be detected in M18GA while PCA production was inhibited
      dramatically in it. Results indicate that promotion of PCA and inhibition of Plt
      production in M18G do result from the inactivation of gacA gene. It suggests that
      the production of antibiotics in strain M18 is differentially mediated by the
      gacA.

PMID- 16110958
TI  - [Expression of hydantoin hydrolase gene in Escherichia coli].
AB  - Hydantoin hydrolase with responsibility for the ring opening of hydantoin is one
      of the components of hydantoin utility enzymes of Arthrobacter BT801 which can
      convert 5-benzylhydantoin into L-phenylalanine. The expression of hydantoin
      hydrolase gene (hyuH) is very important in elucidation of mechanisms of bio
      catalysis and its application in asymmetry synthesis of amino acids. To improve
      the production and activity of the enzyme, the hydantoin hydrolase gene was
      amplified by PCR and cloned into E. coli by using vector pT221. The hydantoin
      hydrolase gene was highly expressed in E. coli BL21 (DE3) under the control of T7
      promoter. A protein band about 50kD was detected by SDS-PAGE in the recombinant
      cell lysate. The objective protein in BL21 (DE3)/pT221-hyuH accounted for 40% of
      total cellular protein, mostly in soluble form. The products in the recombinant
      strain showed biological activity.

PMID- 16110959
TI  - [Cloning of a laccase gene from Flammulina velutipes and study on its expression
      in Pichia pastoris].
AB  - Laccase(EC1.10.3.2) can be used for enzymatic detoxification of lignocellulosic
      hydrolysates. By using molecular techniques such as RACE (rapid amplification of
      cDNA ends) and Genome-Walking, a laccase gene and its corresponding full-length
      cDNA were cloned from Flammulina velutipes and designated as glccFv and IccFv.
      The sequences were submitted to GenBank, and the accession numbers obtained were
      AY485826 and AY450406, respectively. Analysis of amino acids sequence suggested
      that one laccase from Polyporus ciliatus possessed the highest homology with the
      protein encoded by lccFv showing for 72%. The ORF (open reading frame) of lccFv
      was transformed into Pichia pastoris strain GS115 through the P. pastoris
      expression vector pHBM906, which contains both the promoter and transcription
      terminator of the AOX1 gene. The recombinant laccase LCCFv was detected from the
      engineering strain GS115 (pHBM557) which was fermented with BMMY liquid medium
      and induced by 1.0% (V/V) methanol at 20 degrees C with the highest expression
      level (0.1070 U/mL). The optimal reaction temperature of LCCFv that secreted from
      P. pastoris GS115(pHBM557) was 45 degrees C, the optimal reaction pH value was
      pH3.9 and the thermostability and pH stability were very well under the optimal
      conditions.

PMID- 16110960
TI  - [Co-expression of beta-subunit with other subunits of Qbeta replicase].
AB  - In researches involving in vitro protein synthesis and self-replication system,
      Qbeta replicase is one of the key enzymes, which are demanded for the high
      availability. Qbeta replicase is a RNA-dependent RNA polymerase of Qbeta
      coliphage. It consists of four subunits (alpha, beta, gamma, and delta subunit),
      where the beta-subunit is encoded by the viral genome, while the other three
      subunits are host proteins normally involved in protein synthesis, namely,
      ribosomal protein S1 (alpha), elongation factors EF-Tu (gamma) and EF-Ts (delta).
      To increase the production of the Qbeta replicase holoenzyme, several types of
      expression vectors, including pKK, pET and others, were employed to produce Qbeta
      replicase. However, the beta-subunit was almost in the precipitate fraction.
      Considering that the four subunits of Qbeta replicase holoenzyme are in
      equivalent molar ratio and the amount of the subunits, ribosomal S1 and EF-Ts,
      being produced by the host cells is relatively low, co-expression of beta-subunit
      with the other three subunits was performed to know whether the availability of
      the host subunits is the contributing factor for the solubility of the Qbeta
      replicase. pBAD33-rep was constructed by cloning the beta-subunit gene into pBAD
      33, a pACYC derivative, and pET21a(+) was employed as expression vector for the
      three other subunits. Among the different combinations of co-expression
      experiments, solubility was found to slightly increase by SDS-PAGE analysis when
      the beta-subunit was co-expressed with EF-Tu-Ts. And the replicase activity assay
      showed this soluble enzyme is in active form. The expression of beta-subunit was
      enhanced by decreasing the level of inducer IPTG in co-expression, and more
      soluble enzyme were obtained.

PMID- 16110961
TI  - [Purification and properties of endoinulinase from Chaetomium sp].
AB  - An endoinulinase produced by Chaetomium sp. C34 was purified to electrophoretic
      homogeneity, with recovery of 7.7% activity and purification factor of 30.8 fold
      by five steps including ammonium sulfate precipitation, DEAE-cellulose, Q
      sepharose Fast Flow, Sephacryl S-200 and Pre-Packed Hydrophobic Column. Its
      subunit molecular weight was estimated to be about 66kD by SDS-PAGE. The optimum
      temperature and pH of the enzyme activity were 50 approximately 55 degrees C and
      6.0 respectively. The K(m) and V(max) values for inulin were 0.199 mmol/L and 115
      micromol/(mg x min) respectively. Cu2+ completely inhibited inulinase activity.
      An appreciable loss of activity was observed in presence of NBS, Mn2+, Zn2+, Fe2+
      and EDTA. A ratio of inulinase activity to invertase activity (I/S) of 20 was
      found in purified inulinase. The endoinulinase hydrolyzed inulin and liberated
      inulooligosaccharides. But it lacked activity toward melezitose or raffinose.

PMID- 16110962
TI  - [Study on low-temperature alkaline lipase from Bohaisea-9145].
AB  - Lipase-overproducing marine yeast Bohaisea-9145 isolated from the Bohai sea
      region was identified as psychrotrophlic Yarrowia lipolytica. The optimum
      composition of culture medium was ground soybean 4%, rice bran 4%, peanut power
      4%, crude peanut oil 0.5%, MgSO4 0.05%, KH2PPO4 0.2%. The optimum temperature and
      pH were 26 +/- 1 degrees C pH5.0, the time of fermentation cycle was 23h. The
      lipase activity was improved to 258.67 U/mL through optimization, four-fold more
      than that of initial strain. The lipase displayed maximum activity at pH 8.5, 35
      degrees C and was stable within the range of pH 4.0 - 9.0 at low temperature. It
      had high thermosensitivity, good compatibility with familiar metal ions and
      chemical reagents. It was antioxidant and had strong resistance to high salinity.
      As a novel marine low-temperature lipase, it has promising prospect in many
      fields, especially as an additive of detergent.

PMID- 16110963
TI  - [Antimicrobial susceptibility in vitro of 32 drugs against pig Streptococcus
      isolates in China].
AB  - A number of 65 Streptococcus species isolated from diseased pigs were surveyed
      for in vitro minimal inhibitory concentration (MIC) to 32 drugs by microdilution
      test. Clinical categorization of isolates as susceptible or resistant was based
      on MIC interpretative standards of the National Committee for Clinical Laboratory
      Standards(NCCLS). None of the strains were susceptible to all antimicrobial
      compounds tested and most strains (96.6%) were multidrug-resistant. High level
      resistance to streptomycin was also detected. Resistance to sulfonamides (92.3% -
      98.3%), aminoglycosides (70.8% - 78.5%), lincosamides (66.2% - 64.6%),
      tetracyclines (72.3%) and macrolides (53.8% - 67.7%) were most frequent, then
      beta-lactam (18.5% - 56.9%) and quinolones (36.9% - 78.5%) resistance, while all
      strains were susceptible to florfenicol, 78.5% strains were susceptible to
      Taimulin. All resistant strains to beta-lactam were tested for beta-lactamase
      production and the results were negative.

PMID- 16110964
TI  - [The decrease of the activity of electron transfer chain of Torulopsis glabrata
      enhanced pyruvate productivity].
AB  - Torulopsis glabrata CCTCC M202019 was mutated by ethidium bromide to screen for
      respiratory-deficient mutants. Seven mutants that produced pyruvate higher than
      that of the parent were subjected to the tests of the capability assimilating
      fermentable substrate (glucose) and non-fermentable substrates (glycerol and
      acetate) to characterize true respiratory-deficient mutants. Mutants RD-16, RD-17
      and RD-18 were unable to assimilate acetate or glycerol and were therefore
      identified as respiratory-deficient mutants. Compared to the parent strain, the
      growth the intracellular ATP content of those mutants decreased by 21% - 29% and
      15% - 21%, respectively, while the glucose consumption per cell and the pyruvate
      production per cell of those mutants were enhanced by 20.7% - 30.7% and 30.7% -
      55.5%, respectively. Qualitative analysis of cytochromes involved in electron
      transfer chain showed that mutants RD-16 and RD-18 lacked both cytochrome aa3 and
      b, while mutant RD-17 lacked cytochrome b. Enzymes analysis indicated that the
      activities of ATPase, succinate-cytochrome c reductase (complex I ), complex I +
      III , complex II + III, and complex IV of those mutants decreased by 14.6% -
      22.2%, 34% - 41%, 38.6% - 52.6%, 21% - 25%, and 150% - 630%, respectively.
      However, increased glucose consumption per cell was not observed in those
      mutants, which might be due to that the NADH generated in glycolysis can not be
      completely oxidized via electron transfer chain. To avoid the accumulation of
      NADH, 2.1 mmol/L acetaldehyde was added to the culture broth of mutant RD-17 at
      26h of fermentation. Using this strategy, the amount of pyruvate produced
      increased by 21.6% while the fermentation time was shortened from 62h to 48h.

PMID- 16110965
TI  - Assessment the genetic diversity of Auricularia strains by two PCR-based typing
      methods.
AB  - Two PCR-based methods, enterobacterial repetitive intergenic consensus-PCR (ERIC
      PCR) and randomly amplified polymorphic DNA (RAPD), were adopted for
      differentiating Auricularia strains. Taken the similarity coefficient as 75%, 29
      strains of three Auricularia species were grouped into 6 and 9 clusters by RAPD
      and ERIC, respectively. The dendrogram from ERIC exhibited two distinct parts,
      one representing A. auricula and the other A. polytricha, but the dendrogram from
      RAPD failed to clearly distinguish between these two species. However, both
      methods similarly revealed high homology between A. fuscosuccinea and A.
      auricula. The homology relationships among the three species obtained from ERIC
      were validated by Southern hybridization. The analyses showed that RAPD is able
      to differentiate mainly at the species level, while ERIC is effective at the
      strain level and therefore more consistent with cultivation characteristics. The
      results indicate that the method of ERIC-PCR is more rapid and reliable than
      RAPD, and may substitute for RAPD in research related to the genetic
      identification and genetic diversity in Auricularia.

PMID- 16110966
TI  - [Study on isolation and systematic taxonomy of strains of genus Nesterenkonia].
AB  - Four Gram-positive, Nesterenkonia-like strains were isolated from hypersaline
      soils collected from Xinjiang Province, China and East of Egypt. The four strains
      were studies using a polyphasic approach, which included morphological
      observation, growth pH and temperature rang, tolerance to NaCl, KCl, MgCl12 x
      6H2O, CaCl2, enzyme profiles, chemotaxonomy, (G + C) mol% content, 16S rDNA
      sequences analysis and DNA-DNA hybridization, and the only two type strains of
      the genus Nesterenkonia, Nesterenkonia halobia DSM 20541T and Nesterenkonia
      lacusekhoensis DSM 12544T were used as control. The test results showed the four
      isolates belonged the genus Nesterenkonia, but they had great differences from
      the other two valid species of the genus Nesterenkonia, and thus they should
      represent four new species of this genus.

PMID- 16110967
TI  - [Isolation and identification Alicyclobacillus from concentrated apple juice
      processing].
AB  - The forty-five strains of bacteria have been isolated from concentrated apple
      juice. All of them can grow at K agar (pH 4.0), but can't grow at LB palate (pH
      7.0). By using heat resistance test, 38 strains of these bacteria could be
      classified into 3 groups according to their spore-forming time. 33 strains of
      them had the same spore-forming time as DSM 3922, which could produce spores
      within 48 h when cultivated at 45 degrees C; 3 strains of them could grow very
      fast and produced spores within 17 h; and 3 strains of them produced spores 48h
      later. Based on the results of 16S rDNA PCR-RFLP analysis, 7 strains of unknown,
      probably new species and 5 reference strains were selected for 19 phenotypic
      characteristics test and the result were analyses by UPGMA. The results of
      phenotypic characteristics test had good agreement with 16S rDNA PCR-RFLP
      analyses, that the 7 strains were different from all the 5 reference strains,
      they are new species of Alicyclobacillus.

PMID- 16110968
TI  - [Analysis of bacterial composition of the pink mat from spectacles hot spring in
      Tengchong by culture-independent approach].
AB  - The bacterial composition of the pink mat was studied by culture-independent
      approach. 23 complete 16S rDNA sequences were obtained. According to the
      sequences alignment and analysis of comparability, the bacteria of the pink mat
      was consisted of Proteobacteria, Firmicutes, Bacteroidetes, Actinobacter,
      Deinococcus-thermus, Aquificals. And compared with bacterial composition of the
      mats from Octopus spring in Yellowstone Park and Haegindi and Fluidir spring,
      Olkelduhals, Grensdalur spring in Iceland, the pink mat in spectacles spring had
      highest bacterial diversity among them because it perhaps included lots of
      bacteria at lower temperature. And the result indicated the same community lived
      in the same niche and Aquficales was dominant group among bacterial composition
      of the mat in higher temperature and near-neutral hot spring.

PMID- 16110969
TI  - [Cloning and expression of tyrosinase-encoding gene (mel) of Bacillus
      thuringiensis and its initial research of application].
AB  - Tyrosinase, which is encoded by Tyrosinase gene (mel), is the key enzyme in the
      process of melanin formation in animals, plants and microorganisms. Using the
      primers designed by comparing the conserved domain of tyrosinase, a DNA fragment
      was amplified which contain the mel gene from Bacillus thuringiensis 4D11. The
      recombinant E. coli EMB1179 was gained by subcloning this DNA fragment onto the
      vector pGEM-7zf and transformed it into E. coli DH5alpha. EMB1179 express the
      tyrosinase activity and produce melanin under the presence of L-tyrosin. The
      effect of melanin on survival of E. coli was also determined. The results showed
      that the melanin produced by EMB1179 effectively increased its resistance against
      UV light.

PMID- 16110970
TI  - [Cloning of -tubulin gene and their correlation with conferred carbendazim
      resistance of Colletotrichum gloeosporioides Penz in mango].
AB  - The total DNA isolated from MBC-resistant and MBC-sensitive isolates of
      Colletotrichum gloeosporioides Penz (C.g.M) of mango were used as templates in
      PCR amplification using consensus oligo nucleotide primers designed according to
      the known sequence data of beta-tubulin-encoding gene (tub 1 and tub2) of
      Colletotrichum gloeosporioides f. sp. aeschynomene (C. g. A). Only the primers
      designed according to C. g. A tub2 amplified specific fragments. These amplified
      fragments were cloned and sequenced. The results showed that these fragments have
      1344bp and deduced 447 amino acid, which were highly homologous to C.g.A tub2.
      MBC-resistant isolates did not carry the allelic mutation at amino acid codes 198
      and 200 of beta-tubulin gene in comparison with the sensitive isolates. However,
      the amino acid altered in codes 181, 237 and 363.

PMID- 16110971
TI  - [Cloning and expression of gB gene of infectious laryngotracheitis virus in M.
      smegmatis].
AB  - Firstly, the complete gB gene of a domestic isolation stain were amplified by
      PCR, and the 2.6 kb gene fragment was obtained. Then the recombinant plasmid pY
      alpha-gB was constructed by cloning PCR product into pY-alpha vector, and the
      shuttle expression plasmid pR-alpha-gB was constructed by cloning the hsp-alpha
      gB gene into the downstream sequences of pRR3 vector. The recombinant plasmid was
      identified by restriction enzyme digestion and the sequence analysis, which was
      electrophoreted into M. smegmatis mc2 155. At last, the expressed gB proteins
      were successfully detected by ELISA and Western blot, which seems to be
      immunogenic crucially. The recombinant bacterial stain M. smegmatis mc2 155 (pR
      alpha-gB)could protect SPF chick embryo from one lethal dose of ILTV.

PMID- 16110972
TI  - [Cloning, expression and purification of human heat shock protein GP96 gene in
      Escherichia coli].
AB  - Heat shock protein gp96 is a member of HSP90 families. It can elicits both innate
      and adaptive immune responses. Generally it is essential to obtain enough amounts
      of pure gp96 to meet the needs of study and application. But the recombinant gp96
      in E. coli is easy to degrade and form aggregates in certain conditions. In the
      experiment, first cloned human gp96 gene into pET-30a vector and expressed the
      recombinant in E. coli Blstar. Then purified gp96 by Ni-affinity column, anion
      exchange column and Gel-filtration in turn. In the end, removes most degraded
      fragments, aggregates and obtains certain amount of soluble gp96, which make an
      foundation for further investigations of the protein.

PMID- 16110973
TI  - [Study on screening methord of aerobic denitrifiers].
AB  - After domesticating activated sludge to enrich aerobic denitrifier, 105 strains
      were isolated from it. 25 strains with over 50% of TN removal rate were screened
      by measuring TN. It was proved that they can produce nitrate respiration under
      aerobic condition by measuring the concentration of NO2(-) -N , NO3(-) -N and N2.
      The denitrification process of the 24 strains is NO3(-) -N -->NO2(-) -N --> N2.
      Moreover, it was found that there were no obvious competition function between
      NO3- and NO2-. It is deduced that aerobic denitrification can help to realize
      shortened simultaneous nitrification and denitrification and nitration speed is
      more rapid via feedback effect.

PMID- 16110974
TI  - [Progress in type III secretion system].
AB  - Many Gram-negative bacteria use the type III secretion system (TTSS) to inject
      toxin proteins into host cells, then cause the plague disease, typhoid fever,
      diarrhea disease etc. Chaperone proteins is one of four components of MTSS and
      play an important role in helping the secretion of toxin proteins. Although these
      proteins had been found for almost ten years, the detailed function of chaperones
      is enigmatic. In this review, a brief introduction is given about the progress of
      classification, function of chaperones and characteristics of the interactions
      between chaperones and substrates.

PMID- 16110975
TI  - [Application of denaturing gradient gel electrophoresis and temperature gradient
      gel electrophoresis in microbial molecular ecology].
AB  - In recent years, denaturing gradient gel electrophoresis (DGGE) and temperature
      gradient gel electrophoresis (TGGE) are well-established molecular tools in
      microbial molecular ecology that allows the study of diversity and dynamics of
      microbial communities. The technique is reliable, reproducible rapid and
      inexpensive. Here, the principle, the limitations and potentials application of
      DGGE/TGGE techniques are introduced in this paper.

PMID- 16110976
TI  - Better the devil you know? A precautionary approach to using amphipods and
      daphnids in endocrine disruptor studies.

PMID- 16110977
TI  - Sorption of benzidine and 3,3'-dichlorobenzidine to lake sediments. 1.
      Conceptualization and development of a multiparameter model.
AB  - Aromatic amines, such as benzidine and 3,3'-dichlorobenzidine (DCB), are part of
      the dyes and pigments manufacturing process. The prolonged use of these
      carcinogenic chemicals in the past generation has introduced a significant amount
      of contamination to the environment. Their persistency in several mediums has
      sparked a number of studies in an attempt to develop predictive tools of their
      fate and transport in the environment. In this study, benzidine and DCB batch
      isotherms were developed and evaluated. The sediment samples were variable in
      composition, ranging from sandy to silty-clay sediment samples. The batch
      isotherms were then analyzed using high-performance liquid chromatography.
      Subsequently, a multiparameter model (MPM) that accounted for partitioning,
      covalent bonding, and cation exchange was developed and tested in an effort to
      understand the various mechanisms. Results proved the proposed model to be
      effective in predicting sorption of aromatic amines to lake sediments. The
      findings suggest that the MPM can provide a better understanding of the sorption
      process of aromatic amines than more conventional models.

PMID- 16110978
TI  - Widespread detection of N,N-diethyl-m-toluamide in U.S. streams: comparison with
      concentrations of pesticides, personal care products, and other organic
      wastewater compounds.
AB  - One of the most frequently detected organic chemicals in a nationwide study
      concerning the effects of wastewater on stream water quality conducted in the
      year 2000 was the widely used insect repellant N,N-diethyl-m-toluamide (DEET). It
      was detected at levels of 0.02 microg/L or greater in 73% of the stream sites
      sampled, with the selection of sampling sites being biased toward streams thought
      to be subject to wastewater contamination (i.e., downstream from intense
      urbanization and livestock production). Although DEET frequently was detected at
      all sites, the median concentration was low (0.05 microg/L). The highest
      concentrations of DEET were found in streams from the urban areas (maximum
      concentration, 1.1 microg/L). The results of the present study suggest that the
      movement of DEET to streams through wastewater-treatment systems is an important
      mechanism that might lead to the exposure of aquatic organisms to this chemical.

PMID- 16110979
TI  - Effect of urea on degradation of terbuthylazine in soil.
AB  - Pesticide and nitrate contamination of soil and groundwater from agriculture is
      an environmental and public health concern worldwide. The herbicide
      terbuthylazine (CBET) has replaced atrazine in Italy and in many other countries
      because the use of the latter has been banned because of its adverse
      environmental impacts. Unlike atrazine, knowledge about the fate of CBET in soil
      is still not extensive, especially regarding its transformation products, but
      recent monitoring data show its occurrence and that of its main metabolite,
      desethyl-terbuthylazine (CBAT), in groundwater above the limit of 0.1 microg/L
      established by European Union Directive and Italian legislation. The objective of
      this work was to investigate if the presence of the fertilizer urea affects CBET
      degradation in the soil. Laboratory CBET degradation experiments in the
      presence/absence of urea were performed with microbiologically active soil and
      sterilized soil. Terbuthylazine degradation rates under the different
      experimental conditions were assessed, and the formation, degradation, and
      transformation of the metabolite CBAT were also studied. Terbuthylazine
      degradation was affected by the presence of urea, in terms both of a higher
      disappearance time of 50% of the initial concentration and of a lower amount of
      CBAT formed. These findings have practical implications for the real-life
      assessment of the environmental fate of triazine herbicides in agricultural areas
      since these herbicides are frequently applied to soils receiving ureic
      fertilizers.

PMID- 16110980
TI  - Analysis of estrogens in sediment from a sewage-impacted urban estuary using high
      performance liquid chromatography/time-of-flight mass spectrometry.
AB  - We describe a highly selective and sensitive method for determination of estrone
      (E1) and beta-estradiol (E2) in sediments, using high-performance liquid
      chromatography/time-of-flight (HPLC-ToF) mass spectrometry. The method involved
      sequential cleanup of sediment extracts over solid phase extraction cartridges,
      normal phase HPLC, and immunoaffinity extraction, which combine to remove
      coeluting matrix interferences. Resulting method detection limits (0.03 and 0.04
      ng/g for E1 and E2, respectively) are sufficient to determine E1 and E2 in
      estuarine sediments collected from sewage-impacted Jamaica Bay (New York, NY,
      USA). The ToF analyzer has a higher resolution (>6,000) than quadrupole mass
      analyzers and can provide accurate mass estimation to within 2 mDa, which helped
      in distinguishing steroids from isobaric matrix interferences. The E1 and E2 were
      internally mass calibrated with respect to their coeluting surrogate standards,
      and the mass measurement error was between 1.1 and 1.4 mDa. The levels of E1 and
      E2 ranged between 0.07 to 2.52 and 0.05 to 0.53 ng/g, respectively. The measured
      concentrations of steroids in sediments correlated closely with other wastewater
      tracers. Despite the low concentrations of sediment-associated estrogens, their
      predicted estrogenic potency exceeds that of other measured estrogenic
      contaminants.

PMID- 16110981
TI  - Effects of bioturbation on cadmium transfer and distribution into freshwater
      sediments.
AB  - To investigate bioturbation effects on cadmium (Cd) fluxes from overlying water
      to sediments, indoor microcosms were developed. The bioturbating organisms were
      freshwater tubificid worms. Three experimental conditions were studied during 56
      d. The three conditions were contaminated water column ([Cd]: 20 microg/L) with
      or without worms and uncontaminated water column with worms. Cadmium vertical
      profiles were determined in the pore water and in the sediments, based on six
      layers (0-0.5, 0.51, 1-2, 2-3, 3-5, 5-12 cm). Dissolved oxygen, manganese,
      sulfate, and particulate manganese were measured. Bioturbation was analyzed using
      conservative fluorescent particulate tracers. Bioturbation increased Cd flux into
      the sediments by close to a factor of two. Scavenging of Cd was more efficient in
      the bioturbated sediments because particles and adsorption sites for Cd were
      renewed at the sediment-water interface. Tubificids also increased the thickness
      of the Cd-enriched layer. Metals adsorbed on particles at the sediment surface
      were distributed by bioadvection, which predominated the mixing processes.
      Bioturbation also modified the vertical profiles of dissolved and particulate
      manganese and dissolved sulfate but not the profiles of dissolved oxygen. These
      results indicate that the advective transport of particles by bioturbation and
      their subsequent modification by redox reactions accelerates the trapping of
      metals in sediments.

PMID- 16110982
TI  - Solid-phase microextraction for predicting the bioavailability of 2,4,6
      trinitrotoluene and its primary transformation products in sediment and water.
AB  - Disposable solid-phase microextraction fibers (SPMEs) were used to measure the
      availability of 2,4,6-trinitrotoluene (TNT) and its two primary transformation
      products, 2-amino-4,6-dinitrotoluene (2ADNT) and 4-amino-2,6-dinitrotoluene
      (4ADNT). The SPMEs (85-microm polyacrylate) and sediment-dwelling oligochaetes
      (Tubifex tubifex) were exposed to TNT-spiked sediment, to TNT-spiked sediment
      amended with activated carbon, and to TNT-, 2ADNT-, and 4ADNT-spiked water.
      Sediment concentration was a poor predictor of bioavailability in unamended and
      carbon-amended sediments (r2 = 0.14-0.73) The activated carbon amendment reduced
      the bioavailability of compounds in carbon-amended sediment, causing the
      relationships between Tubifex concentrations and sediment concentrations to
      differ significantly between unamended and carbon-amended sediment for all
      compounds. In contrast, SPME TNT concentrations predicted Tubifex TNT
      concentrations (r2 = 0.54-0.79). and regression models did not differ
      significantly among the three TNT-spiked matrices. The SPME 2ADNT and 4ADNT
      concentrations also were predictive of Tubifex 2ADNT and 4ADNT concentrations (r2
      = 0.44-0.90). Relationships between Tubifex concentrations and SPME
      concentrations were the same between unamended and carbon-amended TNT-spiked
      sediments for 2ADNT and 4ADNT; however, the relationship in sediment (pooled
      data) differed from the relationship found in 2ADNT- and 4-ADNT-spiked water. The
      SPMEs provided carbon amendment-independent measures of ADNT availability in
      sediment and matrix-independent measures of TNT availability among the three
      matrices. The SPMEs show promise for predicting bioavailable organic compounds in
      sediment and water.

PMID- 16110983
TI  - Individual and combined toxicity of nitriles and aldehydes to Raphidocelis
      subcapitata.
AB  - A closed-system algal toxicity test with no headspace was applied to evaluate the
      toxicity of 11 aldehydes and two nitriles to Raphidocelis subcapitata. Algal
      growth rate and dissolved oxygen (DO) production were used as the test endpoints.
      Compared to literature data, our test results based on the endpoint of DO
      production is 2.5 to 257 times more sensitive than the conventional algal batch
      tests. In addition, our analyses show that different relative toxicity
      relationships may be observed when different test methods or different endpoints
      are applied. The test alga was found to be quite sensitive to aldehydes, and a
      quantitative structure-activity relationship (QSAR) relationship was established
      based on the n-octanol/water partition coefficient (log Kow). This study also
      evaluated the combined effects of aldehydes and nitriles. Four synergistic joint
      actions related to malononitrile were identified. On the other hand, most of the
      combined effects between aldehydes and acetonitrile were antagonistic. In
      general, we find that greater-than-additive effects mainly are associated with
      toxicants displaying flat dose-response curves, and less-than-additive effects
      may be related to certain steep-slope chemicals. Model analyses show that the
      above mixture toxicity behavior may be due to response addition or response
      multiplication joint action modes.

PMID- 16110984
TI  - An in vitro study of the interaction of sea-nine with rat liver mitochondria.
AB  - The interactions of the antifouling compound Sea-Nine with rat liver mitochondria
      have been studied. The results indicate that low doses of this compound inhibit
      adenosine 5'-triphosphate (ATP) synthesis. Further investigations indicate that
      ATP synthesis inhibition should be due to an interaction of Sea-Nine with the
      succinic dehydrogenase in the mitochondrial respiratory chain.

PMID- 16110985
TI  - Factors influencing persistent organic pollutant concentrations in the Atlantic
      white-sided dolphin (Lagenorhynchus acutus).
AB  - Assessing the trends of persistent organic pollutants (POPs) in cetaceans is
      difficult because of age and gender influences on accumulation. Persistent
      organic pollutants bioaccumulate and are poorly metabolized; hence,
      concentrations may increase with age in males while females reduce their POP
      burden through parturition and lactation. Age and gender effects on contaminant
      concentrations are species specific because of life history and reproductive
      strategies. These influences must be understood in order to elucidate and assess
      lifetime POP exposure. The objectives of this study were to determine baseline
      POP concentrations in blubber samples from the Atlantic white-sided dolphin
      (Lagenorhynchus acutus) and to investigate life history and other influences,
      such as metabolism, on these concentrations. Forty-seven L. acutus blubber
      samples collected from mass stranding events in Massachusetts, USA (1993-2000),
      and archived in the National Marine Mammal Tissue Bank at the National Institute
      of Standards and Technology (Gaithersburg, MD, USA) were analyzed for 55
      polychlorinated biphenyl congeners (PCB; 55 congeners), five polybrominated
      diphenyl ether (PBDE) congeners, and organochlorine pesticides (toxaphene, DDT
      and metabolites, mirex, dieldrin, chlordanes, hexachlorocyclohexanes,
      hexachlorobenzene, and endosulfans) by gas chromatography/mass spectrometry (GC
      MS). Ages for 19 animals were determined from growth layer groups on decalcified,
      stained thin tooth sections. Total PCBs (sigmaPCB; sum of 55 congeners) were the
      contaminants present in the highest concentrations in all age classes (0.5-63
      microg/g wet mass) followed by sum of DDTs (0.50-43 microg/g wet mass), toxaphene
      (0.055-31 microg/g wet mass), chlordanes (0.30-24 microg/g wet mass), and PBDEs
      (0.12-4.0 microg/g wet mass). Body length had a greater statistical influence
      than age on contaminant burdens in L. acutus. Contaminant burdens decreased with
      length in both male and female L. acutus, suggesting metabolic elimination and/or
      growth dilution in males and off-loading via lactation in females.

PMID- 16110986
TI  - An environmentally relevant concentration of estrogen induces arrest of male
      gonad development in zebrafish, Danio rerio.
AB  - The aim of the present study was to elucidate how full life-cycle exposure to
      estrogens impacts zebrafish development and reproduction, compared to partial
      life-cycle exposure only, and whether the estrogen-induced effects in zebrafish
      are reversible or irreversible. Zebrafish were exposed in a flow-through system
      to an environmentally relevant concentration (3 ng/L) of the synthetic estrogen
      17alpha-ethinylestradiol (EE2) either from fertilization until the all-ovary
      stage of gonad development (i.e., 42 d postfertilization [DPF] in our experiment)
      or from fertilization until the reproductive stage (i.e., 118 DPF). Reversibility
      of the estrogen-induced effects was assessed after 58 d of depuration in EE2-free
      water until 176 DPE Early life exposure led to a lasting induction of plasma
      vitellogenin (VTG) in adult females but altered neither the sex ratio nor the
      reproductive capabilities. Full life-cycle exposure resulted in elevated VTG
      concentrations and caused gonadal feminization in 100% of exposed fish and thus
      inhibited reproduction. Two types of ovaries were observed in continuously
      exposed adult fish, immature ovaries with primary growth stage oocytes only and
      mature ovaries containing the full range of all oocyte maturation stages. Fish
      with immature ovaries had plasma VTG levels like control males, while fish with
      mature ovaries had female-like VTG levels. The effects of full life cycle
      exposure were at least partly reversible, and 26% of fish of the previous all
      female cohort developed fully differentiated testes. These findings suggest that
      continuous estrogen exposure had arrested the developmental transition of the
      gonads of genetic males from the early all-ovary stage to functional testes.
      After the exposure had ceased, however, these males apparently were able to
      accomplish testicular differentiation.

PMID- 16110987
TI  - Hepatic retinoids of bullfrogs in relation to agricultural pesticides.
AB  - Agricultural pesticides often have been cited as a factor affecting indigenous
      amphibian populations, but possible effects of pesticides and other factors
      associated with agricultural practices are understood poorly. Adult bullfrogs
      (Rana catesbeiana) were collected within the Yamaska River basin (Quebec, Canada)
      in subwatersheds representing low, medium, and high agricultural activities and
      53 pesticides were analyzed in surface water. More pesticides were detected in
      subwatersheds associated with high agricultural activities like Riviere Noire and
      Riviere a la Barbue and pesticide concentrations were higher compared to the
      other study sites. Female and male body weights differed between sites. In the
      case of males, body weight was significantly less at Riviere a la Barbue. Liver
      retinol stores were decreased significantly in male bullfrogs from Riviere Noire,
      although total retinyl esters concentrations varied between sites having the
      highest concentration at Yamaska-Nord where the agricultural activity was
      considered low. The ratio of hepatic retinyl palmitate to retinol tended to be
      higher for male bullfrogs from Riviere Noire and Riviere a la Barbue. These
      results suggest that factors associated with intensive agricultural practices may
      affect the body weight and retinoid stores in male bullfrogs living in these
      agroecosystems.

PMID- 16110988
TI  - Novel biomarkers of perchlorate exposure in zebrafish.
AB  - Perchlorate inhibits iodide uptake by thyroid follicles and lowers thyroid
      hormone production. Although several effects of perchlorate on the thyroid system
      have been reported, the utility of these pathologies as markers of environmental
      perchlorate exposures has not been adequately assessed. The present study
      examined time-course and concentration-dependent effects of perchlorate on
      thyroid follicle hypertrophy, colloid depletion, and angiogenesis; alterations in
      whole-body thyroxine (T4) levels; and somatic growth and condition factor of
      subadult and adult zebrafish. Changes in the intensity of the colloidal T4 ring
      previously observed in zebrafish also were examined immunohistochemically. Three
      month-old zebrafish were exposed to ammonium perchlorate at measured perchlorate
      concentrations of 0, 11, 90, 1,131, and 11,480 ppb for 12 weeks and allowed to
      recover in clean water for 12 weeks. At two weeks of exposure, the lowest
      observed-effective concentrations (LOECs) of perchlorate that induced
      angiogenesis and depressed the intensity of colloidal T4 ring were 90 and 1,131
      ppb, respectively; other parameters were not affected (whole-body T4 was not
      determined at this time). At 12 weeks of exposure, LOECs for colloid depletion,
      hypertrophy, angiogenesis, and colloidal T4 ring were 11,480, 1,131, 90, and 11
      ppb, respectively. All changes were reversible, but residual effects on
      angiogenesis and colloidal T4 ring intensity were still present after 12 weeks of
      recovery (LOEC, 11,480 ppb). Whole-body T4 concentration, body growth (length and
      weight), and condition factor were not affected by perchlorate. The sensitivity
      and longevity of changes in colloidal T4 ring intensity and angiogenesis suggest
      their usefulness as novel markers of perchlorate exposure. The 12-week LOEC for
      colloidal T4 ring is the lowest reported for any perchlorate biomarker in aquatic
      vertebrates.

PMID- 16110989
TI  - Effects of fomesafen, alone and in combination with an adjuvant, on plankton
      communities in freshwater outdoor pond mesocosms.
AB  - Ecotoxicological effects of the diphenyl ether herbicide fomesafen, applied alone
      or in combination with the adjuvant Agral 90 (mixture of polyethoxylated
      derivatives of nonylphenol), were assessed on planktonic communities in 18-m3
      outdoor mesocosms during a nine-month study. Four mesocosms were treated with
      fomesafen only (nominal concentration: 40 microg/L), four were treated with the
      mixture fomesafen-Agral 90 (nominal concentration: 40 microg/L and 90 microg/L,
      respectively), and four were kept as the controls. Five treatments were performed
      every three weeks from April 18, 2000. Mean (+/- standard error [SE]) values of
      fomesafen concentration in water of 62.5 (+/-5.3) and 19.4 (+/-7.6) microg/L were
      measured at the end of the treatment period in fomesafen- and mixture-treated
      mesocosms, respectively. Fomesafen, either alone or in mixture with Agral 90, had
      a significant positive effect on the abundance and biovolume of Cyanobacteria,
      Cryptophyceae, Dinophyceae, and Bacillariophyceae. Chlorophyceae were inhibited
      by the herbicide and laboratory toxicity tests confirmed that green algae were
      more sensitive toward fomesafen than other algal classes. A positive effect of
      treatments on phytoplankton taxonomic diversity also was observed, indicating
      that, like natural disturbances of intermediate strength, xenobiotics sometimes
      may enhance the diversity of algal communities. Fomesafen alone did not have any
      clear effect on zooplankton. Abundance of calanoid copepods was reduced
      significantly in the mixture-treated ponds, suggesting either a direct effect of
      the adjuvant and/or an enhancement of herbicide toxicity by Agral 90. The
      abundance of other zooplanktonic herbivorous groups increased due to a reduced
      competition for food for herbivorous species and a higher availability of preys
      for predators. No algal bloom was observed in the treated ponds, presumably
      because of grazing pressure and the low availability of nutrients.

PMID- 16110990
TI  - Potentiation of the vitellogenic response to 17alpha-ethinylestradiol by cortisol
      in the fathead minnow Pimephales promelas.
AB  - The effects of elevated plasma cortisol levels on vitellogenin (VTG) induction
      were examined in the fathead minnow (Pimephales promelas) in an attempt to
      evaluate the potential influence of stress on this commonly used biomarker of
      estrogenicity. Two separate experiments were conducted in which fish plasma
      cortisol was elevated to various levels for 14 d by noninvasive additions of
      cortisol to the aquaria water. Fathead minnows were exposed to either cortisol
      alone, 17alpha-ethinylestradiol (EE2) alone, or a combination of the two
      hormones, and plasma levels of VTG as well as liver expression of VTG mRNA were
      measured. Both experiments gave similar results, with an exposure to 4 ng/L of
      EE2 resulting in significantly greater levels of plasma VTG in the presence of,
      compared to that in absence of, cortisol, whereas exposure to cortisol alone at
      concentrations between 144 and 800 microg/L had no effect on plasma VTG levels.
      This potentiation of the EE2-induced vitellogenesis by cortisol was dose
      dependent, with plasma VTG reaching 125, 167, and 295% of the values obtained
      with EE2 alone when 144, 360, and 800 microg/L of cortisol, respectively, were
      added to the water. Liver mRNA results were consistent with plasma VTG, although
      they generally were more variable. The present study demonstrates that cortisol
      does not independently induce vitellogenesis but can potentiate estrogen-induced
      VTG synthesis in fathead minnow. The implications of these findings for the use
      of VTG as a biomarker of estrogenicity are discussed.

PMID- 16110991
TI  - Influence of sediment quality on the responses of benthic invertebrates after
      treatment with the fungicide triphenyltin acetate.
AB  - After decades of pollution, benthic communities in floodplain lake ecosystems are
      likely to be exposed to a diverse assortment of sediment-bound historical
      toxicants and nutrients as well as pulses of newly discharged or deposited
      toxicants. The aim of this study was therefore to analyze the effects of
      background sediment pollution on the responses of benthic invertebrates to an
      experimental toxic shock in a laboratory setting. Sediment from a relatively
      clean and a historically polluted floodplain lake located along the River Waal, a
      branch of the River Rhine, The Netherlands, was selected, and the fungicide
      triphenyltin acetate (TPT) was used as the acute stressor. Juvenile stages of the
      mayfly Ephoron virgo and the midge Chironomus riparius were chosen as test
      organisms because of their different response to sediment-bound toxicants and
      food quantity and quality. Our results demonstrated that the type of sediment had
      no effect on survival and growth of C. riparius when exposed to sediment
      associated TPT and that E. virgo was more affected by sediment-associated TPT on
      clean sediment than on polluted sediment. For the mayfly, no cumulative response
      of the historical pollution and the recent toxic shock was observed. This
      observation is discussed in view of the variable content of organic matter,
      acting both as food and as sorbent, and leads to the hypothesis that a very
      strong sequestering of TPT in historically polluted sediment prevents expression
      of toxic effects.

PMID- 16110992
TI  - Joint effects of density and a growth inhibitor on the life history and
      population growth rate of the midge Chironomus riparius.
AB  - Results of previous laboratory studies suggest that high population density often
      buffers the effects of chemical stressors that predominately increase mortality.
      Mortality stressors act to release more resources for the survivors and,
      therefore, produce less-than-additive effects. By contrast, growth stressors are
      expected to have opposite results or more-than-additive effects. We investigated
      the effects of a growth inhibitor (lufenuron) on larval growth and survival of
      Chironomus riparius and examined its joint effects with density on population
      growth rate (PGR). Exposure to 60 microg/kg sediment or greater inhibited larval
      growth, and exposure to 88 microg/kg or greater often resulted in mortality
      before reaching emergence. The effects of lufenuron, however, differed with
      population density. At 88 microg/kg, mortalities and, to a lesser extent, reduced
      fecundity resulted in a reduction in PGR at low density. Conversely, when
      populations were initiated at high density, PGR was similar to that of controls,
      because the few survivors reached maturity sooner and started producing offspring
      earlier. The effect of density as a growth stressor therefore was stronger than
      the effect of lufenuron, which had effects similar to those of a mortality
      stressor and produced less-than-additive effects. Long-term studies under field
      conditions, however, are needed before less-than-additive effects are considered
      to be the norm.

PMID- 16110993
TI  - Toxicity of alpha-, beta-, (alpha + beta)-endosulfan and their formulated and
      degradation products to Daphnia magna, Hyalella azteca, Oncorhynchus mykiss,
      Oncorhynchus kisutch, and biological implications in streams.
AB  - The static acute toxicities of alpha-endosulfan, beta-endosulfan, (alpha + beta)
      endosulfan, endosulfan sulfate (their transformation product), and formulated
      materials were determined for a representative freshwater amphipod (Hyalella
      azteca), cladoceran (Daphnia magna), and salmonid fish (Oncorhynchus mykiss).
      Acute lethality tests also were conducted on these organisms and coho salmon
      (Oncorhynchus kisutch) by exposing them to simulated field water endosulfan
      concentrations, using either a single compound and/or in combinations. As well,
      growth/survival bioassays of H. azteca were carried out in simulated sediment
      endosulfan concentrations that were detected in farm ditches contiguous to fish
      streams in the Lower Fraser Valley (BC, Canada). All materials tested were very
      highly toxic to these nontarget aquatic indicator organisms. As the most potent
      compound, alpha-endosulfan is about 1.3, 6.6, and 58 times more toxic than the
      beta-isomer to Daphnia, rainbow trout, and Hyalella, respectively. Some possible
      biological and toxicological implications of our findings are discussed in the
      context of endosulfan concentrations found in farm ditches flowing to fish
      streams in the Lower Fraser Valley.

PMID- 16110994
TI  - RNA/DNA ratios as a sublethal endpoint for large-scale toxicity tests with the
      nematode Caenorhabditis elegans.
AB  - Caenorhabditis elegans increasingly is attractive as a toxicity test organism,
      particularly as a model system to study mechanisms of toxicity at a molecular
      level and the way that these lead to whole organism and population level effects.
      Inhibitions of growth, reproduction, movement, and feeding rate all have been
      proposed as sublethal toxicity endpoints. These endpoints are more sensitive than
      24-h acute toxicity endpoints, but assays are much more time consuming, making
      them difficult to use in mass screening. The RNA/DNA ratio, after 48-h exposure
      to metals, has median effective concentration (EC50) values of 0.05, 0.6, 6.1,
      and 35 mg/L for Cu, Pb, Cd, and Zn, respectively. This makes it a slightly more
      sensitive toxicity endpoint than reduction of individual growth after 72-h
      exposure to the same concentrations. This facilitates the near-simultaneous
      assessment of sublethal toxicity in many nematode samples. The constant cell
      number of C. elegans means that different stages in the life history have very
      different RNA/DNA ratios even in the absence of toxins. So, RNA/DNA ratios can be
      used only on prereproductive, age-synchronized cultures. Assessing the sublethal
      toxicity of metals to C. elegans shows that it is sensitive particularly to Cu.

PMID- 16110995
TI  - Influence of duration of exposure to the pyrethroid fenvalerate on sublethal
      responses and recovery of Daphnia magna straus.
AB  - This study compares lethal and sublethal responses of Daphnia magna Straus
      exposed to fenvalerate continuously (21 d) and as a pulse (24 h). Survival was
      reduced more severely in the continuous- than in the pulse-exposure regime.
      Complete mortality occurred at 1 microg/L for continuous exposure and at 3.2
      microg/L for pulse exposure. Regarding reproductive endpoints, fenvalerate
      delayed the age at first reproduction. At the beginning of the reproductive phase
      (day 10), this delay resulted in a reduction of the neonates per living female at
      similar concentrations in both exposure regimes (0.3 and 0.1 microg/L for
      continuous and pulse exposure, respectively). The population growth rate was
      inhibited in continuous and pulse exposure at 0.3 and 0.6 microg/L, respectively.
      However, the effects of fenvalerate in the pulse exposure were transient. After
      21 d, a recovery to values close to the controls occurred with respect to the
      total neonates per female and the population growth rate over a broad range of
      concentrations from 0.1 up to 1 microg/L. In contrast, no substantial recovery
      occurred in the continuous-exposure regime.

PMID- 16110996
TI  - Uptake and accumulation of sediment-associated 4-nonylphenol in a benthic
      invertebrate (Lumbriculus variegatus, freshwater oligochaete).
AB  - In the present work, the oligochaete Lumbriculus variegatus was exposed for 56 d
      to lake sediment spiked with 4-nonylphenol (4-NP), which is a breakdown product
      of alkylphenol polyethoxylates, an important class of nonionic surfactants.
      During the exposure period, the content of 4-NP was determined in the
      oligochaetes, sediment, overlying water, and pore water in order to monitor the
      distribution of the 4-NP in the compartments of the test system. Concentration of
      4-NP in L. variegatus increased linearly over the course of the test, with an
      uptake rate coefficient of 1.9 x 10(-2) (+/- 0.2 x 10(-2); [g carbon/(g lipid x
      h)]). No steady state was reached at the end of the exposure period, suggesting
      that the elimination of 4-NP by the organism was negligible. Ingested sediments
      played an important role in the accumulation of 4-NP in L. variegatus, which may
      achieve very high 4-NP body concentrations. The 56-d biota sediment accumulation
      factor (BSAF) was 24 +/- 7 g carbon/g lipid. L. variegatus also was exposed to 4
      NP-contaminated field sediment, and field oligochaetes and sediments were
      collected for 4-NP pollution assessment in aquatic ecosystem. The 4-NP uptake
      with natural sediment was in accordance with that measured with spiked sediments,
      suggesting that the bioavailability of sediment-associated 4-NP for L. variegatus
      was not affected by 4-NP sediment concentration and abiotic sediment
      characteristics. The BSAFs measured in field oligochaetes, ranging from 39 to 55
      g carbon/g lipid, was relatively higher than the bioaccumulation factor measured
      in laboratory tests. The results suggest that 4-NP concentration can reach high
      levels in benthic oligochaetes; this can be an important way of exposure for
      their pelagic predators.

PMID- 16110997
TI  - Short-term exposures of fish to perfluorooctane sulfonate: acute effects on fatty
      acyl-coa oxidase activity, oxidative stress, and circulating sex steroids.
AB  - This study investigated the effects of exposure to waterborne perfluorooctane
      sulfonate (PFOS) on oxidative stress and reproductive endpoints in fish.
      Exposures utilized species commonly used in toxicological testing, including the
      fathead minnow (Pimephales promelas) and rainbow trout (Oncorhynchus mykiss), as
      well as relatively insensitive taxa such as creek chub (Semotilus atromaculatus),
      spottail shiner (Notropis hudsonius), and white sucker (Catostomus commersoni).
      In all fish species, short-term (14-28 d) exposure to PFOS produced only modest
      mortality at concentrations consistent with environmental spill scenarios.
      However, PFOS consistently increased hepatic fatty acyl-CoA oxidase activity and
      increased oxidative damage, as quantified using the 2-thiobarbituric acid
      reactive substances assay. Plasma testosterone, 11-ketotestosterone, and 17beta
      estradiol titers were often elevated with PFOS exposure. Vitellogenin, the egg
      yolk precursor protein, was occasionally altered in the plasma with PFOS
      exposure, but responses varied with maturity. Oviposition frequency and egg
      deposition in fathead minnow were not significantly impaired with PFOS exposure,
      despite a trend toward progressive impairment with increasing exposure
      concentrations. Although short-term PFOS exposure produced significant impacts on
      biochemical and reproductive endpoints in fish at concentrations consistent with
      environmental spills, the impact of long-term exposure to environmentally
      relevant concentrations of PFOS is unclear.

PMID- 16110998
TI  - Long-term variability of zooplankton populations in aquatic mesocosms.
AB  - The natural variability on a spatial and temporal scale was examined in the
      zooplankton community of mesocosms from Syngenta Crop Protection AG (Stein,
      Switzerland), with the focus on improving the experimental design and evaluation
      of mesocosm studies. Analysis was performed using zooplankton data collected
      during a three-year period in 3 (1996 and 1998) to 12 (1997) ponds.
      Interreplicate variability was measured as the variance among the 3 to 12
      replicates at each sampling date. Temporal variation was examined as seasonal
      variability by comparing different sampling dates within a year and as year-to
      year variation by comparing pooled data year by year. Univariate and multivariate
      methods were used for the evaluation of population and community data,
      respectively. Results from the present study indicate that because of the low
      interreplicate variability, only data from high-abundance species could be
      evaluated with a precision able to detect effects less than 20%. For the majority
      of the zooplankton populations, abundances were lower than 10 organisms/L, with
      frequent zero counts resulting in a weak evaluation of the data with a precision
      able to detect effects of greater than 20 and 110%. Ordination analysis of the
      community data from the three years revealed that approximately 29% of the total
      variance could be explained by year-to-year differences, whereas 11% could be
      attributed to seasonal variability within a year. The residual variance can be
      attributed to interreplicate variability and sampling error. These results were
      in line with findings for individual populations. The present analysis
      demonstrated that the inherent variability of a system should be investigated for
      a proper design and evaluation of mesocosm studies and promotes the use of
      multivariate tools for a more comprehensive interpretation of mesocosm data.

PMID- 16110999
TI  - Bioavailability models for predicting acute and chronic toxicity of zinc to
      algae, daphnids, and fish in natural surface waters.
AB  - Bioavailability models predicting acute and/or chronic zinc toxicity to a green
      alga (Pseudokirchneriella subcapitata), a crustacean (Daphnia magna), and a fish
      (Oncorhynchus mykiss) were evaluated in a series of experiments with spiked
      natural surface waters. The eight selected freshwater samples had varying levels
      of bioavailability modifying parameters: pH (5.7-8.4), dissolved organic carbon
      (DOC, 2.48-22.9 mg/L), Ca (1.5-80 mg/L), Mg (0.79-18 mg/L), and Na (3.8-120
      mg/L). In those waters, chronic zinc toxicity (expressed as 10% effective
      concentrations [EC10]) varied up to 20-fold for the alga (72-h EC10 from 27.3 to
      563 microg Zn/L), and approximately sixfold for the crustacean (21-d EC10 from
      59.2 to 387 microg Zn/L), and fivefold for the fish (30-d LC10, lethal
      concentration for 10% of the organisms, from 185 to 902 microg Zn/L). For P.
      subcapitata a refined bioavailability model was developed by linking an empirical
      equation, which predicts toxicity expressed as free Zn2+ activity as a function
      of pH, to the geochemical speciation model WHAM/Model V. This model and
      previously developed acute and/or chronic biotic ligand models for D. magna and
      0. mykiss generally predicted most effect concentrations by an error of less than
      a factor of two. In waters with pH > 8, however, chronic toxicity to D. magna was
      underestimated by a factor 3 to 4. Based on the results of this validation
      exercise and earlier research, we determined applicability ranges for pH (6-8)
      and Ca (5-160 mg/L) in which all three developed models are valid. Within these
      ranges, all three models may be considered useful tools for taking into account
      bioavailability in regulatory assessments of zinc.

PMID- 16111000
TI  - Growth inhibition as indicator of stress because of atrazine following multiple
      toxicant exposure of the freshwater macrophyte, Juncus effusus L.
AB  - Atrazine is a herbicide used most frequently in North America, but it usually is
      encountered in mixtures of agrochemicals. Few atrazine exposure studies have been
      conducted using mixed pesticides; therefore, little data are available to suggest
      reliable means of discerning effects attributable to atrazine. The common
      freshwater macrophyte, Juncus effusus L., was exposed in 66 mesocosms to atrazine
      at two nominal concentrations (96 and 192 microg/L) with varying concentrations
      of chlorpyrifos, monosodium methanearsonate, and monomethylmercury. Exposure
      levels represented typical levels that might follow runoff or direct-spray
      application in enclosed waterbodies. Using shoot density and number of shoots
      shorter than 25 cm per unit area as response measurements, the growth effects of
      atrazine, even in varying pesticide mixes, could be detected as early as 16 d
      after initial exposure. Further growth effects specifically caused by atrazine
      also could be detected following a second exposure to the same toxicant mixture.
      Mesocosm tests offer greater control of natural variability than would be found
      in the natural environment and offer more realistic conditions than traditional
      laboratory/greenhouse studies. Therefore, in field testing, growth measurements
      should be accompanied by other confirmatory tests, such as pesticide
      concentrations in tissue and, possibly, chlorophyll concentrations, for measuring
      specific toxic effects of atrazine and other pesticides.

PMID- 16111001
TI  - Effects of hardness, chloride, and acclimation on the acute toxicity of sulfate
      to freshwater invertebrates.
AB  - The acute toxicity of sulfate to Ceriodaphnia dubia, Chironomus tentans, Hyalella
      azteca, and Sphaerium simile was assessed to support potential updates of
      Illinois (USA) sulfate criteria for the protection of aquatic life. The mean
      lethal concentrations to 50% of a sample population (LC50s), expressed as mg S04(
      2)/L, in moderately hard reconstituted water (MHRW) were as follows: 512 mg/L for
      H. azteca, 2,050 mg/L for C. dubia, 2,078 mg/L for S. simile, and 14,134 mg/L for
      C. tentans. At constant sulfate (approximately 2,800 mg/L) and hardness (106
      mg/L), survival of H. azteca was positively correlated with chloride
      concentration. Hardness also was found to ameliorate sodium sulfate toxicity to
      C. dubia and H. azteca, with LC50s for C. dubia increasing from 2,050 mg SO4(
      2)/L at hardness = 90 mg/L to 3,516 mg SO4(-2)/L at hardness = 484 mg/L. Using a
      reformulated MHRW with a similar hardness but higher chloride concentration and
      different calcium to magnesium ratio than that in standard MHRW, the mean LC50
      for H. azteca increased to 2,855 mg/L, and the LC50 for C. dubia increased to
      2,526 mg/L. Acclimation of C. dubia to 500 and 1,000 mg SO4(-2)/L for several
      generations nominally increased mean LC50 values compared with those cultured in
      standard MHRW.

PMID- 16111002
TI  - Ecotoxicity of sodium fluoroacetate (compound 1080) to soil organisms.
AB  - Sodium fluoroacetate (compound 1080) is applied as a vertebrate pesticide in New
      Zealand for control of introduced mammalian pests. Despite its widespread use,
      little is known about the soil ecotoxicity of 1080. Therefore, the hazard of 1080
      to soil invertebrates, plants, and soil microorganisms was evaluated in a series
      of controlled laboratory tests. No earthworm (Eisenia fetida) mortality was
      reported with 1080 exposures up to 865 mg/kg soil. The lowest-observable-effect
      concentration and the median effect level for earthworm reproduction were 100 and
      90 mg/kg soil, respectively, for cocoon production and 100 and 160 mg/kg soil,
      respectively, for juvenile production. Lettuce (Lactuca sativa) was more
      sensitive than oats (Avena sativa) to 1080. Lettuce seedling emergence and
      seedling shoot growth were adversely affected at a soil concentration of 7 mg/kg.
      The presence of 1080 in soil at concentrations up to 1 g/kg soil did not affect
      the ability of soil microorganisms to mineralize nitrogen. Furthermore, nitrate
      mineralization was not inhibited in soil treated with the urine of 1080-poisoned
      possums (Trichosurus vulpecula). The data collectively indicate that 1080-related
      effects on soil organisms occur at levels well above those that have been
      measured in soil (<0.1 mg/kg) following application of 1080 in baits for
      vertebrate pest control in New Zealand.

PMID- 16111003
TI  - Comparative toxicity of two oil dispersants, superdispersant-25 and corexit 9527,
      to a range of coastal species.
AB  - The acute toxicity of the oil dispersant Corexit 9527 reported in the literature
      is highly variable. No peer-reviewed data exist for Superdispersant-25 (SD-25).
      This study compares the toxicity of the two dispersants to a range of marine
      species representing different phyla occupying a wide range of niches: The marine
      sediment-dwelling amphipod Corophium volutator (Pallas), the common mussel
      Mytilus edulis (L.), the symbiotic snakelocks anemone Anemonia viridis (Forskal),
      and the seagrass Zostera marina (L.). Organisms were exposed to static dispersant
      concentrations for 48-h and median lethal concentration (LC50), median effect
      concentration (EC50), and lowest-observable-effect concentration (LOEC) values
      obtained. The sublethal effects of 48-h exposures and the ability of species to
      recover for up to 72 h after exposure were quantified relative to the 48-h
      endpoints. Results indicated that the anemone lethality test was the most
      sensitive with LOECs of 20 ppm followed by mussel feeding rate, seagrass
      photosynthetic index and amphipod lethality, with mussel lethality being the
      least sensitive with LOECs of 250 ppm for both dispersants. The results were
      consistent with current theory that dispersants act physically and irreversibly
      on the respiratory organs and reversibly, depending on exposure time, on the
      nervous system. Superdispersant-25 was found overall to be less toxic than
      Corexit 9527 and its sublethal effects more likely to be reversible following
      short-term exposure.

PMID- 16111004
TI  - Influences of maternal exposure on the tolerance and physiological performance of
      Daphnia magna under mercury stress.
AB  - We examined the tolerance development to mercury (Hg) by a population of
      freshwater zooplankton (Daphnia magna) with different pre-exposure histories to
      Hg. The growth and reproductive performance of the F1 offspring as affected by
      the maternal (F0) and offspring (F1) exposures was quantified. The F0 daphnids
      exposed to 2.5 and 25 nM of Hg for 4 d and followed by 4 d of depuration had
      elevated levels of Hg and metallothionein-like proteins (MTLPs), as well as
      higher tolerance to Hg toxicity than the control daphnids. The higher Hg
      tolerance may be attributed to the higher proportion of Hg partitioned to the
      MTLPs. Moreover, significant enhancement of Hg tolerance also was found in the F1
      offspring originating from the F0 mothers exposed to 25 nM of Hg, but there was
      no significant induction of MTLPs in these F1 offspring when compared to the
      offspring from the control mothers. The Hg tissue concentrations in the F1
      neonates were approximately 25% of those in the F0 adults. However, there was
      similar Hg tolerance in the F2 offspring originating from both the control and Hg
      exposed F0 mothers, indicating that the Hg tolerance in the daphnids disappeared
      two generations after Hg contamination. Further exposure of the F1 offspring to
      different Hg concentrations (1.5 and 15 nM for 28 d) indicated that maternal
      exposure history did not affect their growth and reproductive performance, which
      solely were influenced by the offspring exposure. Unexpectedly, the F1 offspring
      exposed to Hg had significantly higher final wet weights and reproductive rates
      than the control groups, suggesting the possibility of Hg hormesis. Furthermore,
      the maternal exposure had no effect on the Hg accumulation and the MTLP
      concentrations in the F1 offspring. Therefore, we concluded that the Hg tolerance
      might disappear quickly once the Hg contamination was removed and the maternal
      exposure history was not important in determining the physiological performance
      and Hg accumulation of the subsequent generations.

PMID- 16111005
TI  - Population-level effects of male-biased broods in eelpout (Zoarces viviparus).
AB  - Effects of environmental pollutants are most obvious when mortality is increased.
      However, there are other nonlethal factors that may affect population size
      significantly. Endocrine disruption as a mechanism of action for pollutants
      recently has received much attention. Observations of effects likely caused by
      endocrine disruptors in pulp mill effluents have been made on several fish
      species, e.g., male-biased broods in eelpout (Zoarces viviparus). Fewer females
      represent a lower fecundity and could have dramatic effects on the population. In
      this study, a population viability analysis of the effects of skewed primary sex
      ratios in the eelpout was conducted using a female-based matrix population model.
      The model is age-structured with one deterministic version and another that
      incorporates environmental stochasticity. The model showed that the deterministic
      and stochastic growth rates in an undisturbed population (50% female fry) were
      1.172 and 1.075, respectively, compared to 1.097 and 1.007 using the lowest
      proportion of female fry observed (38.7%). When primary sex ratios were more male
      biased, the probability of pseudoextinction increased. Model simulations showed
      that the probability of a decreased population size to 5% of the initial within a
      100-year time horizon was 44.7% with 38.7% female fry compared to only 7.7% for
      an undisturbed population.

PMID- 16111006
TI  - Acute and chronic toxicity of mercury to early life stages of the rainbow mussel,
      Villosa iris (Bivalvia: Unionidae).
AB  - Mercury (Hg) contamination is receiving increased attention globally because of
      human health and environmental concerns. Few laboratory studies have examined the
      toxicity of Hg on early life stages of freshwater mussels, despite evidence that
      glochidia and juvenile life stages are more sensitive to contaminants than
      adults. Three bioassays (72-h acute glochidia, 96-h acute juvenile, and 21-d
      chronic juvenile toxicity tests) were conducted by exposing Villosa iris to
      mercuric chloride salt (HgCl2). Glochidia were more sensitive to acute exposure
      than were juvenile mussels, as 24-, 48-, and 72-h median lethal concentration
      values (LC50) for glochidia were >107, 39, and 14 microg Hg/L, respectively. The
      24-, 48-, 72-, and 96-h values for juveniles were 162, 135, 114, and 99 microg
      Hg/L, respectively. In the chronic test, juveniles exposed to Hg treatments > or
      = 8 microg/L grew significantly less than did control organisms. The substantial
      difference in juvenile test endpoints emphasizes the importance of assessing
      chronic exposure and sublethal effects. Overall, our study supports the use of
      glochidia as a surrogate life stage for juveniles in acute toxicity tests.
      However, as glochidia may be used only in short-term tests, it is imperative that
      an integrated approach be taken when assessing risk to freshwater mussels, as
      their unique life history is atypical of standard test organisms. Therefore, we
      strongly advocate the use of both glochidia and juvenile life stages for risk
      assessment.

PMID- 16111007
TI  - Association between lymphocyte proliferation and polychlorinated biphenyls in
      free-ranging harbor seal (Phoca vitulina) pups from British Columbia, Canada.
AB  - Recent pinniped die-offs have led to the speculation that persistent organic
      pollutants (POPs) are immunomodulatory, making individuals more susceptible to
      viral infections. Eighteen healthy harbor seal (Phoca vitulina) pups (aged 3-4
      weeks) were live-captured from southern British Columbia, Canada, and maintained
      temporarily in captivity for an immunotoxicological assessment. The relationships
      between mitogen-induced peripheral blood lymphocyte proliferation and blubber
      concentrations of three major immunotoxic POP classes (the polychlorinated
      biphenyls [PCBs], polychlorinated dibenzo-p-dioxins [PCDDs], and the
      polychlorinated dibenzofurans [PCDFs]) were evaluated. A significant body weight
      independent positive correlation was observed between both T-cell mitogen
      (phytohemagglutinin [PHA])- and B-cell mitogen (lipopolysaccharide [LPS])-induced
      lymphocyte proliferation and the blubber concentrations of total PCB. Best subset
      regression analysis revealed that total PCBs, and not total PCDD or total PCDF,
      explained 24 and 29% of the changes in both T-cell mitogen-and B-cell mitogen
      induced lymphocyte proliferation, respectively. Further regression analysis
      performed on the PCB classes measured in this study showed that di-ortho PCBs
      accounted for 25 and 30% of the changes in both T-cell and B-cell lymphocyte
      proliferation, respectively. Results suggest that POPs, and PCBs in particular,
      are associated with changes in lymphocyte proliferation, something that could
      result in increased susceptibility to infections in harbor seal pups. Further
      research is needed to evaluate the relative roles of natural and contaminant
      related influences on the immune system of marine mammals.

PMID- 16111008
TI  - Aquatic herbicide exposure increases salamander desiccation risk eight months
      later in a terrestrial environment.
AB  - Contaminants and climate change may be factors in amphibian declines. However,
      few studies have explored their joint impacts on postmetamorphic amphibians, a
      life stage of great importance to amphibian population dynamics. Here, we examine
      the effects of premetamorphic exposure (mean exposure of 64 d) to ecologically
      relevant concentrations of the globally common herbicide atrazine (0, 4, 40, 400
      microg/L) on the behavior and water retention of lone and grouped
      postmetamorphic, streamside salamanders, Ambystoma barbouri. Salamanders exposed
      to > or = 40 microg/L of atrazine exhibited greater activity, fewer water
      conserving behaviors, and accelerated water loss four and eight months after
      exposure compared to controls. No recovery from atrazine exposure was detected
      and its effects were independent of the presence of conspecifics. These results
      are consistent with the hypothesis that adverse climatic conditions and
      contaminants can interact to harm post-metamorphic amphibians; however, they
      suggest that these two stressors need not be experienced simultaneously to do so.
      These results emphasize the importance of considering both latent and cumulative
      effects of temporally linked stressors in ecotoxicology.

PMID- 16111009
TI  - Fish full life-cycle testing for 17beta-estradiol on medaka (Oryzias latipes).
AB  - We studied the chronic effects of 17beta-estradiol (E2) on the reproductive
      status of medaka (Oryzias latipes) over two generations under continuous exposure
      to assess its hazard on this species. The exposure of parental (F0) medaka to E2
      was begun on embryos within 12 h postfertilization and continued for up to 101 d;
      the assessment endpoints included embryological development, hatching, posthatch
      survival, growth, sexual differentiation, reproduction, and hepatic vitellogenin
      (VTG) levels under flow-through exposure to E2 at each mean measured
      concentration of 0.939, 2.86, 8.66, 27.9, and 92.4 ng/L. Eggs (F1) spawned from
      the F0 fish at 98, 99, and 100 d posthatch were also examined for hatchability,
      survival after hatching, growth, sexual differentiation, and hepatic VTG level
      until 59 d posthatch. In the F0 medaka, no concentration-related effect of E2 was
      observed on hatching, posthatch mortality, and growth. However, we observed
      abnormal sex differentiation, induction of VTG, and reproductive impairment in a
      dose-dependent manner. The lowest-observed-effect concentration and no-observed
      effect concentration of E2 for these effects were 8.66 and 2.86 ng/L,
      respectively. In the F1 medaka treated with E2 at < or = 8.66 ng/L, however, dose
      dependent effects were not observed in any parameter. The results indicate that
      E2 can have significant effects on reproductive potential of medaka at
      concentrations as low as 8.66 ng/L, suggesting that the ecological risk of E2 is
      higher than that of weak estrogens, such as nonylphenol and octylphenol.

PMID- 16111010
TI  - Multiple sublethal chemicals negatively affect tadpoles of the green frog, Rana
      clamitans.
AB  - Many habitats may be exposed to multiple chemical contaminants, particularly in
      agricultural areas where fertilizer and pesticide use are common; however, the
      singular and interactive effects of contaminants are not well understood. The
      objective of our study was to examine how realistic, sublethal environmental
      levels of ammonium nitrate fertilizer (0, 10, 20 mg/L and ammonium chloride
      control) and the common insecticide carbaryl (0 or 2.5 mg/L) individually and
      interactively affect the development, size, and survival of green frog (Rana
      clamitans) tadpoles. We reared tadpoles for 95 d in outdoor 1,000-L polyethylene
      ponds. We found that the combination of carbaryl and nitrate had a negative
      effect on development and mass of tadpoles compared to the positive effect that
      either contaminant had alone. Presence of carbaryl was generally associated with
      short-term increases in algal resources, including ponds exposed to both carbaryl
      and nitrate. However, with exposure to nitrate and carbaryl, tadpole mass and
      development were not positively affected as with one chemical stressor alone. The
      combination of these sublethal contaminants may reduce the ability of amphibians
      to benefit from food-rich environments or have metabolic costs. Our study
      demonstrates the importance of considering multiple stressors when evaluating
      population-level responses.

PMID- 16111011
TI  - Oxidative stress and endocrine endpoints in white sucker (Catostomus commersoni)
      from a river impacted by agricultural chemicals.
AB  - The effects of agricultural chemicals on cortisol secretion, antioxidants, and
      lipid peroxidation were investigated in hepatic and adrenal tissue of white
      sucker (Catostomus commersoni) from a river (Yamaska) that drains an agricultural
      region in Quebec (Canada). Plasma cholinesterase (ChE) activity, used as a
      biomarker of exposure to pesticides, was elevated in fish from the reference site
      compared to fish from the contaminated sites. Plasma concentrations of cortisol
      and thyroid hormones (T3 and T4) were higher in fish from the reference site
      compared to contaminated sites; reduced glutathione (GSH) levels, catalase (CAT),
      and glutathione peroxidase (GPx) activities were higher and lipid peroxidation
      (LPO) was lower. Levels of antioxidants (CAT, Gpx, and GSH) were higher (10-90%)
      and LPO levels were lower (50%) in the liver than in the adrenal tissue. The
      present in situ study provided evidence that antioxidants, lipid peroxidation,
      and plasma hormones were altered in fish sampled in areas impacted by
      agricultural chemicals. Endocrine-disrupting effects were associated with
      oxidative stress. The results suggest that antioxidants and lipid peroxidation
      could be used as markers of contaminant exposure in fish.

PMID- 16111012
TI  - Acute contamination with esfenvalerate and food limitation: chronic effects on
      the mayfly, Cloeon dipterum.
AB  - Results of environmental risk assessments based merely on toxic effects of
      contaminants at the individual level, without consideration of population-level
      effects, may be questionable. The aim of the present study was to investigate how
      limited food resources, resulting in intraspecific competition, could interact
      with the chronic effect of short-term contamination with the insecticide
      esfenvalerate. Larvae of the mayfly, Cloeon dipterum, were exposed to
      esfenvalerate (0.001-100 microg/L) for 1 h and then transferred to indoor
      microcosms containing insecticide-free water, where they were maintained at
      various food levels until emergence. The results showed that short-term exposure
      to 10 or 100 microg/L resulted in acute mortality. Chronic effects on survival
      occurred at concentrations up to three orders of magnitude lower than that
      causing the acute effect (0.01 microg/L). Food limitation increased effects on
      organisms during medium-term observation (8-15 d), but assessment of long-term
      survival rates suggested that the chronic effects of low insecticide
      concentrations could be compensated for, at least regarding some endpoints. The
      authors assume that in limited-food conditions, lethal and sublethal effects
      reduced competition between individuals, resulting in significantly increased
      final survival.

PMID- 16111013
TI  - Biotic ligand model prediction of copper toxicity to daphnids in a range of
      natural waters in Chile.
AB  - The objective of this study was to assess the predictive capacity of the biotic
      ligand model (BLM) for acute copper toxicity to daphnids as applied to a number
      of freshwaters from Chile and to synthetic laboratory-prepared waters. Thirty
      seven freshwater bodies were sampled, chemically characterized, and used to
      determine the copper concentration associated with the 50% of mortality (LC50)
      for Daphnia magna, Daphnia pulex, and Daphnia obtusa (native to Chile). The data
      were then used to run three versions of the acute copper BLM, and the predicted
      LC50s were compared to the observed ones. The same was done with synthetic assay
      media at various hardness and dissolved organic carbon (DOC) levels. The BLM
      versions differed in the affinity constants for some biotic ligand-ion pairs,
      stability constants for inorganic Cu complexes, and assumptions regarding Cu
      binding to DOC. All three versions showed a high degree of predictive
      performance, mostly within a twofold range of observed toxicity values. The D.
      obtusa data set was used to compare water quality criteria (WQC) derived from the
      observed toxicity values with those derived from either the BLM or the U.S.
      Environmental Protection Agency (U.S. EPA) procedure. For most low DOC waters,
      the three procedures generated similar WQCs. For the high-DOC waters, the EPA
      derived criteria were significantly lower, that is, greatly overprotective. The
      results are also discussed in terms of the validation of the BLM for regulatory
      use.

PMID- 16111014
TI  - Monarch ready to take on more Medicare Advantage members.

PMID- 16111015
TI  - Medicare capitation poised for major comeback in 2005.

PMID- 16111016
TI  - Medicare Advantage increases cap payments third straight year.
AB  - Healtn plans that participate in Medicare Advantage got more good news in April
      when the Centers for Medicare & Medicaid Services announced a 4.8% increase in
      capitated payments. It is the third straight year CMS increased rates following
      the passage of the 2003 Medicare Prescription Drug, Improvement and Modernization
      Act, fueling a resurgence in Medicare risk contracting.

PMID- 16111017
TI  - Understanding contracts is one key to improving capitation management.
AB  - Capitated contracts have become much more complex with new provisions for gain
      sharing, pay-for-performance incentives, carve-outs, and updates for new
      technology, pharmaceuticals, and injectables. Use these strategies to protect
      your organization in today's risk contracting environment

PMID- 16111018
TI  - Doctor group sues to keep capitation arrangement.
AB  - An independent practice association has sued Humana Kansas City Inc. over the
      health plan's decision to terminate its capitated contract. The suit alleges
      breach of contract and seeks an injunction to keep the flow of capitated dollars
      coming.

PMID- 16111019
TI  - Hospitals are taking a new accountability.

PMID- 16111020
TI  - How will hospitals get their share of ED funds?

PMID- 16111021
TI  - Women need flexible schedules and challenging assignments.

PMID- 16111022
TI  - [Implementation analysis of public functions of centers of disease prevention and
      control of China].
AB  - OBJECTIVE: To evaluate the implementation of public function and items of the
      centers of disease prevention and control(CDC). METHODS: 161 centers of disease
      prevention and control have been investigated by two-stage stratified sampling.
      The implementation analysis of public function and items of CDC is measured by
      multiplying average operational proportion and average operational degree.
      RESULTS: 1. For investigated centers, the average rate of function implementation
      is 42.9% ,with 56.0% at provincial level and 43.7% at city level, 41.3% for the
      county level; while 49.3% in east areas, 45.4% in middle areas and 35.3% in west
      areas. 2. Among all 7 functional items, the implemented rate of disease
      prevention and control is 54.3%, 65.8% for emergency treatment, 35.0% for
      epidemic situation report and information management of health relative factors,
      31.3% for inspection and control of health risk factors, 39.1% for the laboratory
      examination and evaluation, 36.4% for health education and health promotion, and
      56.7% for technological guidance and application study. CONCLUSION: The
      implemented degree of public function of CDC was generally lower, varied with
      regions and levels. Among 7 public functional items, the emergency treatment
      function had the highest implementation, with the lowest for the inspection and
      control of health relative factors.

PMID- 16111023
TI  - [Operational proportion of the public function and items of 161 centers of
      disease prevention and control in 7 provinces].
AB  - OBJECTIVE: To explicate the operational proportion of public function and items
      of the centers of disease prevention and control (CDC). METHODS: 161 CDC have
      been investigated by two-stage stratified sampling to provide the information
      about the operation of the public function and items of CDC. RESULTS: (1) The
      average operational proportion investigated CDC is 71.7%, the province level
      92.0%, the city level 73.7%, the county level 68.5%. East areas 76.5%, middle
      areas 71.5%, west areas 68.1%. (2) The operational proportion of disease
      prevention and control function and emergency treatment function were higher, but
      that of epidemic situation report and information management of health relative
      factor, inspection and control of health relative factor, and the laboratory
      examination and evaluation were lower. CONCLUSION: Public function and items were
      rather poorly carried out by the centers of prevention and control in China,
      especially those in middle and west areas, and those in counties.

PMID- 16111024
TI  - [Study on differential display genes of tolerant-damage of MRC-5 induced by
      formaldehyde of low dose].
AB  - OBJECTIVE: To observe the differentially expressed genes of the human embryo lung
      fibroblast (MRC-5) induced by formaldehyde (FA) of low dose using fluoro DD-PCR.
      METHODS: The dose-effect relation of FA toxicity to MRC-5 was acquired, No
      observed damage effect or proliferation concentration was used as low dose, and
      obvious damage concentration was used as high dose. MRC-5 was treated with low
      and high dose, and treated with high dose after pretreated with low dose for some
      time. Then Fluoro differential display polymerase chain reaction (Fluoro DD-PCR)
      was used to search differentially expressed genes of the differently treated
      groups of FA. 61 differential display straps were acquired and 11 of them were
      reamplified, cloned, sequenced and blasted. RESULTS: According to the dose-effect
      relation of FA toxicity to MRC-5, 100 micromol/L was choosed as low dose and 10
      mmol/L was choosed as high dose. Samples of differently treated groups were
      amplified by means of fluro-DD-PCR, 61 differentially expressed straps were
      acquired. 11 differential display straps have been cloned, sequenced and blasted.
      Two of them were known genes: one was highly homologous to nuclear factor of
      activated T-cells 5 (NFAT5) and the other was highly homologous to
      tetratricopeptide repeat domain 3(TPRD-3). Nine of them were new genes.
      CONCLUSION: It seemed that FA of low dose could promote MRC-5 proliferation and
      find 61 differentially expressed genes of differently treated groups, and the
      result of clone could provide scientific base for mechanism of FA toxicity
      research.

PMID- 16111025
TI  - [In vivo micronuclei and gene mutation induced by DEN in the lacZ transgenic
      mouse].
AB  - OBJECTIVE: To assess mutagenicity of N-nitrosodiethylamine (DEN) in vivo using
      the lacZ transgenic mouse (Muta Mouse). METHODS: LacZ gene was recovered through
      in vitro packing. Mutant frequencies (MFs) in the lacZ gene of liver, lung and
      bladder were examined after intraperitoneal treatment with DEN (25mg/kg per week
      x 4). Simultaneously, the clastogenicity of DEN was evaluated by the peripheral
      blood micronucleus assay. RESULTS: The mean frequency of micronucleated
      reticulocytes (MNRETs) did not increase by the treatment with DEN. The MFs
      increase above spontaneous levels were apparent in liver and lung, with
      respectively 6.13 - and 3.66 fold increase. The MF of lacZ of bladder was of the
      background level. CONCLUSION: Liver and lung are target organ of genotoxicity in
      vivo induced by DEN with different sensitivity.

PMID- 16111026
TI  - [Effects of 2,5-hexanedione on NGF expression in motor and sensory neuronal cells
      of rats].
AB  - OBJECTIVE: To investigate the effects of 2,5-Hexanedione (2,5-HD), a metabolite
      of n-hexane,on nerve growth factor (NGF) expression in motor and sensory neuronal
      cells of peripheral nervous system of rats. METHODS: Primary cultured dorsal root
      ganglion (DRG) neurons were obtained from new born rats on day 4. The cell line
      VSC4.1 were cultured. The growth condition of cells were observed with a phase
      contrast microscope. Immunohistochemistry technology was used to analyze the NGF
      expression in both VSC4.1 cells and primary cultured DRG cells treated with 4
      different dosages of 2, 5-HD (2.5, 5.0, 10.0, 20.0 mmol/L) respectively for 24
      hours. RESULTS: The NGF expression decreased significantly in both DRG neurons
      and VSC4.1 cells dosed respectively with 5.0,10.0,20.0 mmol/L 2,5-HD in
      comparison with the control group (P < 0.05), with a tendency of dose-effect
      correlation. CONCLUSION: The results suggested that 2,5-HD can decrease the
      endogenous NGF levels in both cultured DRG sensory neurons and VSC4.1 motor
      neuron cells of rats.

PMID- 16111027
TI  - [Effect of formaldehyde on energy metabolism in postnatal rat cortex neurons in
      culture].
AB  - OBJECTIVE: The mechanism of the effect of formaldehyde on CNS which is much
      concerned to formaldehyde poisoning was studied. METHODS: In the present study,
      incubation of postnatal rat cortex neurons in culture with formaldehyde at 1, 2,
      4, 8 mg/L (medium) was carried out to evaluate the effect of formaldehyde on
      energy metabolism. RESULTS: The result of cytochemistry showed a significant down
      regulation of cytochrome oxidase activity after consecutive formaldehyde
      treatment for 4 hours compared with the control (P < 0.01), the significant
      dosage-response relationship was also observed (R value is - 0.92, P < 0.01).
      CONCLUSION: The result demonstrates that excessive exposure of formaldehyde can
      decrease cytochrome oxidase activity in cortex neurons which indicates energy
      metabolism will be decreased and therefore normal physiology function would be
      damaged.

PMID- 16111028
TI  - [Adaptive response induced by low concentration of hydroquinone in human
      embryonic fibroblasts cells].
AB  - OBJECTIVE: To study the adaptive response induced by hydroquinone(HQ) on
      eukaryocyte and its possible mechanism. METHODS: After hydroquinone treatment,
      AlamarBlue reduce rate, LDH release rate were observed to determine the cell
      proliferation and death. Annexin V/propidium iodide (PI) staining was performed
      for each treatment to distinguish viable, early, and late apoptosis or dead
      cells. The total cellular proteins were separated using two- dimensional gel
      electrophoresis and visualized by sliver staining. Digital images were analyzed
      using ImageMaster 2D platinum 5.0 software. The differentially expressed protein
      spots were picked and digested in gel then identified by tandem mass spectrum.
      RESULTS: The results of AlamarBlue reduce rate, LDH leakage and Annexin V-FITC/PI
      staining showed that no effect on cell viability was observed at a concentration
      of 10 micromol/L HQ while 250 micromol/L HQ significantly decreased cell
      viability. Cells pretreated with 10 micromol/L HQ for 12h show increasing
      survival to the following expose to 250 micromol/L HQ. In control MRC-5 cells
      1429 +/- 369 protein spots were detected and, 1453 +/- 307 in low HQ group, 1191
      +/- 393 in high HQ group, and 1107 +/- 247 in adaptive group by two dimensional
      gel electrophoresis. Twenty-four protein spots showed significant change after HQ
      stimulation and 22 protein spots were identified by tandems mass spectra. These
      identified proteins involved in energy metabolism, translation and RNA
      processing, protein folding, redox regulation, cell structure and cell signaling.
      CONCLUSION: Adaptive response can be induced by low concentration of HQ on MRC-5
      cells and cellular adaptation is a complex process involving in a modulation of
      diverse cellular functions.

PMID- 16111029
TI  - [Establishment of reporter gene-based assays for the identification of (anti)
      androgenic effects of chemicals in CHO cells].
AB  - OBJECTIVE: Develop reporter gene-based assays for the identification of (anti)
      androgenic effects of chemicals in CHO cells, explore the antiandrogenic effects
      of 2,4-DDT and methoxychlor. METHODS: Chinese Ovary cells were cotransfected with
      the human androgen receptor expression vector, mouse mammary tumour virus MMTV
      luciferase vector and phRL-SV40 using the transfection reagent Sofast, test the
      luciferase activity. After treatment of the cells for 24 h with
      dihydrotestosterone (DHT), flutamide (FLU), validate the effectiveness and
      specificity, also test the effect of 2,4-DDT and methoxychlor (METH). RESULTS:
      DHT is a potent agonist, 1 x 10(-10) mol/L DHT could result in the enhancement of
      luciferase activity, FLU is a complete antagonist, that confirmed the
      effectiveness and specificity of test system. 2,4-DDT and METH are partial
      antagonists. 3 x 10(-7) mol/L and above 2,4-DDT and METH could inhibit the
      androgenic activity of DHT. CONCLUSION: The assay we developed is doful, 2,4-DDT
      and METH could antagonize the androgenic effects.

PMID- 16111030
TI  - [Effects of prenatal methylmercury exposure on learning and memory ability of
      mice and ultrastructure of hippocampus neurons in mice].
AB  - OBJECTIVE: To study the effects of prenatal methylmercury exposure on learning
      and memory ability of mice and ultrastructure of hippocampus neurons in mice.
      METHODS: Methylmercury in doses of 0 and 4mg/(kg x d) were fed to pregnant mice
      at 7th-9th day after conception. Learning and memory ability of the mice
      offspring was detected. The ultrastructure of hippocampus neurons was observed by
      electron microscope after the completion of the experiment. RESULTS: The learning
      and memory ability of the mice offspring of 4 mg/(kg x d) dose group was lower
      than those of 0 mg/(kg x d) dose group (P < 0.05). Changes in the ultrastructure
      of hippocampus neurons were obvious in 4 mg/(kg x d) dose group as compared with
      the 0 mg/(kg x d) dose group. CONCLUSION: Methylmercury could affect the growth
      and development of central nerve system. The learning and memory ability of mice
      offspring was greatly damaged and the ultrastructure of hippocampus neurons was
      changed by methylmercury.

PMID- 16111031
TI  - [The dose-effect relationship of water fluoride levels and renal damage in
      children].
AB  - OBJECTIVE: To explore the dose-effect relationship of water fluoride levels and
      renal damage in children and observe the difference of renal function between
      high-loaded fluoride people and dental fluorosis people in the same water
      fluoride level region. METHODS: 210 children were divided into seven groups in
      term of drinking water fluoride levels and whether they suffered from dental
      fluorosis. Fluoride concentrations in urine and serum and activities of urine NAG
      and gamma-GT were determined. RESULTS: The urine and serum fluoride of high
      loaded fluoride people and dental fluorosis people increased compared with
      control, moreover fluoride contents in urine and serum increased gradually with
      the increase of fluoride level in drinking water. Urine NAG and gamma-GT
      activities significantly increased in dental fluorosis people from area of 2.58
      mg/L fluoride in drinking water and in those two groups from area of 4.51 mg/L
      fluoride in drinking water. Moreover, there existed an obvious dose-effect
      relationship between the drinking water fluoride concentration and NAG and gamma
      GT activity. CONCLUSION: Over 2.0 mg/L fluoride in drinking water can cause renal
      damage in children, and the damage degree increases with the drinking water
      fluoride content. Renal damage degree is not related to whether the children
      suffered from dental fluorosis and mainly due to water fluoride concentration.

PMID- 16111032
TI  - [Expression and assay in vitro of phage single chain antibody against
      nucleoprotein of influenza virus A type].
AB  - OBJECTIVE: To expression the phage single chain antibody against nucleoprotein of
      influenza virus A type in E. coli strain HB2151 by screening the positive clone
      from the phage antibody library against nucleoprotein, which will prepare for the
      construction of fast leak kit of Influenza virus A type. METHODS: The positive
      clone ratio in the phage antibody library was enriched by three-round continual
      solid panning, ELISA, SDS-PAGE and Western-blot methods were used to analyze the
      protein secreted into the supemants and periplasmic. Affinity chromatography was
      used to purified the protein expressed in periplasmic and the titer was also
      analyzed using ELISA method. RESULTS: 10 clones were screened from96 clones and
      among the 10, there were 3 stronger positive with OD450nm value of 0.469, 0.582
      and 0.507, respectively. The phage single chain antibody against Influenza virus
      A type was primary expressed in periplasmic. The ELISA results were positive even
      if the single chain antibody purified by affinity chromatography was diluted 4096
      folds. CONCLUSION: Using phage antibody library technique, phage single antibody
      against nucleoprotein of influenza virus A type was preliminary expressed in E.
      coli.

PMID- 16111033
TI  - [Expression of sHsps of normal palate and cleft palate during mouse
      embryogenesis].
AB  - OBJECTIVE: To study the expression of sHsps in normal palate and cleft palate
      during mouse embryogenesis. METHODS: At GD10, gestational mice of the treatment
      and the control were administered with 80 mg/kg retinoic acid and the same volume
      vegetable oil separately, and the normal palate and cleft palate of embryos were
      harvested in GD15-GD17. The relative abundance of sHsps of all samples was
      measured by reverse transcript polymerase chain reaction (RT-PCR). RESULTS: In
      the normal limbs, except that there is no expression of Hspb10 at GD17, all the
      other Hsps expressed obviously in GD15-GD17. To the normal palates, the
      expressional abundance of Hsp20, Hsp25, Hsp27, Hsp32, Hspb2, Hspb3, Hspb7 was
      stable, that of Hsp30, Hspb5 was increased following the embryos aging, and the
      expressional peak of Hsp10, Hsp22, Hspb4 occurred at GD16. In GD15-GD17, the
      expressional abundance of Hsp30, Hsp32, Hspb4, Hspb10 of the cleft palates was
      higher than that of the normal palates, but the expressional abundance of Hsp60,
      Hspb5, Hspb9 of the cleft palates was lower than that of the normal palates. The
      expressional models of Hspb9, Hspb 10 of the normal palates were different from
      those of the cleft palates obviously. CONCLUSION: Except that there is no
      expression of HspblO at GD17, all the other Hsps expressed obviously in GD15-GD17
      during normal clefts' development. To different Hsps, there is different
      expressional characteristic. Hsp30, Hsp32, Hspb4, Hspb10 maybe play a protective
      role in the stress action of cleft palate, and Hsp10, Hsp60, Hspb5, Hspb9, Hspb10
      were maybe relative to cleft palate.

PMID- 16111034
TI  - [Detecting the DNA damage of N-ras gene induced by potassium dichromate].
AB  - OBJECTIVE: Applying RDPCR to detect the DNA damage of N-ras gene induced by
      Potassium dichromate METHODS: Preparing single-stranded probes of exon 1 of N-ras
      gene in human. The genomic DNA was treated with Potassium dichromate, then
      amplified by RDPCR and detected by Southern hybridization with the probe.
      RESULTS: The clear hybridized bands can be seen in the position which is induced
      by Potassium dichromate on the dose of 100 micromol/L, but can't be detected on
      the dose over 1000 mol/L. CONCLUSION: It indicates that Potassium dichromate can
      cause the DNA damage of N-ras gene, which should be the key point of its
      carcinogenesis mechanisms.

PMID- 16111035
TI  - [Association of genetic polymorphism of XRCC1 with susceptibility to acute
      childhood leukemia].
AB  - OBJECTIVE: To explore the association between genetic polymorphisms of XRCC1 and
      susceptibility to acute childhood leukemia. METHODS: A case-control study with 63
      childhood leukemia patients and 66 control subjects was conducted to investigate
      the role of three XRCC1 polymorphisms (c. 194, c. 280 and c. 399 ) on
      susceptibility to childhood leukemia. Genotyping was performed using Polymerase
      chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) to
      detect the single nucleotide polymorphisms (SNPs) of XRCC1 gene. RESULTS: There
      was a 2.235-fold increased risk of childhood leukemia for individuals carrying
      XRCC1c. 399 Gin allele (95% CI 1.038 - 4.812) compared with subjects carrying
      Arg/Arg allele, and the OR among boys was 3.110 (95% CI 1.235 - 7.831). No
      interaction was found between X-ray exposure and XRCC1 polymorphisms using
      Logistic regression analysis. CONCLUSION: Polymorphism of XRCC1 gene may
      contribute to the higher risk of childhood leukemia.

PMID- 16111036
TI  - [Effect of flavonoids of ginkgo biloba on anti-oxidizing system of mice after
      acute alcohol administration].
AB  - OBJECTIVE: To investigate the protective effects of flavonoids of ginkgo biloba
      on anti-oxidizing system damaged by acute alcohol administration. METHODS: Adult
      male Kunming mice were employed and divided into randomly flavonoid intervention
      group, normal control and ethanol control group according to body weight. After
      pretreated with flavonoids of ginkgo biloba (96mg/kg bw), the mice in flavonoid
      intervention group ingested alcohol (ethanol 4.8g/kg bw) via i.g. and were
      decapitated after 0.5, 1, 2, 4, 6, 9, and 15 h of ethanol administration. The
      same treatment was carried out on ethanol control group except that physiological
      saline was applied instead of flavonoid of ginkgo biloba. Meanwhile, the normal
      control group was established. RESULTS: The concentration of glutathione (GSH),
      malondialdehyde (MDA) and the activity of glutathione peroxidase (GSH-Px),
      superoxide dismutase (SOD) in the serum and liver were determined. The experiment
      displays that the content of GSH and the activities of GSH-Px and SOD decreased
      rapidly after 1 h of treatment with alcohol and dropped to the lowest level at 4h
      of treatment. After 6h of treatment, these indexes came to the normal level
      rapidly. The level of MDA of serum and liver increased rapidly after 1 h of
      treatment and reached the climax at 4h and 6h respectively. It went back to the
      normal concentration until 15h and 9 h respectively. On a whole, there were
      similar curves between flavonoids intervention group and alcohol control group on
      the indexes. However, to some extent, the supplement of flavonoid of ginkgo
      biloba can prohibit the rise of MDA level and the decline of GSH-Px, SOD, GSH
      which were induced by acute alcohol intakes. CONCLUSION: Flavonoid of ginkgo
      biloba have some protective effects on the damage of anti-oxidizing system of
      mice induced by acute alcohol adminstration.

PMID- 16111037
TI  - [Oxidative damage and apoptosis in NIT-1 cells induced by ethanol].
AB  - OBJECTIVE: To decide whether ethanol induce apoptosis in mouse insulinoma cells
      (NIT-1) and the potential mechanism involved. METHODS: After NIT-1 cells were
      exposed to various concentrations of ethanol, agarose gel electrophoresis was
      used to detected DNA fragmentation. malondialdehyde (MDA) content, glutathione
      (GSH) level, superoxide dismutase(SOD) and glutathione peroxidase (GSH-Px) were
      measured in NIT-1 cells to evaluate the oxidative damage degree. Caspase-3
      relative activity was determined by colorimetric assay. RESULTS: The results
      showed a "DNA ladder" pattern after treated with ethanol in NIT-1 cells. The MDA
      content was higher, the SOD activity, GSH-Px activity and GSH content were lower
      in ethanol group than those of control group. Ethanol increased the caspase-3
      activity by a dose and time dependent manner. CONCLUSION: Higher concentration of
      ethanol induces imbalance of oxidation and antioxidative ability in NIT-1 cells,
      and oxidative stress further leads to apoptosis which may be related to the
      increased caspase-3 activity.

PMID- 16111038
TI  - [Development of methods on detection of enteropathogenic Escherichia coli by
      double PCR in meat and meat product].
AB  - OBJECTIVE: To establish a rapid method for detecting Enteropathogenic Escherichia
      coli (EPEC) in meat and meat product. METHODS: Based on attaching and effacing
      lesion (eaeA gene) and bundle-forming pili (bfpA gene) of EPEC, two pairs of
      primers were designed. Then EPEC in meat and meat product were detected by double
      PCR. RESULTS: The method is rapid and specific. The limit of detection is 10
      cfu/g in 8 - 17 hours. CONCLUSION: A simple, rapid, sensitive and specific PCR
      method can be established to detect EPEC in meat and meat product.

PMID- 16111039
TI  - [Analysis of lactase activities of small intestine mucous membrane by double
      labeled stable isotope technique in subjects with lactase deficiency].
AB  - OBJECTIVE: Low lactase activity in small intestine mucosa is the main reason for
      the occurrence of lactose malabsorption (LM) and lactose intolerance (LI). It
      would be the basis for the research on LM and LI to find an accurate method to
      analyze the activity of lactase. METHODS: In this study, 43 volunteers were
      selected and divided into LM and LI group according to the results of H2 breath
      test and symptoms record. Twenty-five grams of 13C-lactose and 0.5 g 2H-glucose
      in 250ml solution were consumed by all the volunteers. The concentration of total
      plasma glucose, 13C- glucose and 2H-glucose were measured, the ratio of [13C
      glucose]/[2H-glucose] and lactose digestion index (LDI)were calculated which
      could reflect the lactase activities in the mucous membrane of small intestine.
      RESULTS: It was found that there was no significant difference in the
      concentration of total glucose and 13C-glucose, while the LDI in LM group (0.47
      +/- 0.15) was significantly higher than LI group (0.34 +/- 0.14). There was no
      significant relationship between LDI and 6h cumulative breath H2 amount (r =
      0.12, P = 0.46). The 13 C-lactose/2 H-glucose challenged test showed there was
      still residual lactase activity in small intestine. CONCLUSION: It was concluded
      that 13C-lactose/2H-glucosetest can accurately and sensitively determine the
      lactase activity on small intestinal mucous membrane and digestible lactose
      amount.

PMID- 16111040
TI  - [Effect of beta-carotene supplementation on DNA oxidative and alkylation damage
      in rats].
AB  - OBJECTIVE: To investigate the effect of beta-carotene (P-C) supplementation on
      DNA oxidative and alkylation damage in rats. METHODS: Rats were randomly divided
      into five groups. The first group was no beta-C, and the second, the third, the
      forth and the fifth groups were daily supplemented with 0.071, 0.355, 4.28 and
      15.0 mg/(kg x d). The content of plasma VA was analyzed by fluorescent
      spectrometry. DNA damage and oxidative damage induced by H2O2 were detected by
      single-cell gel electrophoresis (SCGE) and O6-Methyl-guanine (O6-MeG) was
      measured by high performance capillary zone electrophoresis. RESULTS: After 8
      weeks trial, the results showed that levels of plasma retinol converted from beta
      C decreased by 135 microg/L in the beta-C deficiency group, which were much lower
      than 276 - 306 microg/L in other four beta-C supplement groups (P < 0.01).
      Intrinsic damage of DNA was more severe in the group of beta-C deficiency than
      the groups supplemented with beta-C (P < 0.01). The lower DNA oxidative damage of
      lymphocyte, which was induced by H2O2, was found in 4.28 mg/(kg x d) group than
      deficiency and other supplement groups (P < 0.05). O6-Methyl-guanine of the
      supplement groups was lower than the beta-C deficient group at the 6th week and
      8th week (P < 0.05). O6-Methyl-guanine did not decreasing with the dose
      increasing and the lowest in the 4.28mg/(kg x d) group. CONCLUSION: Beta-C or
      retinol deficiency and over intake such as 15.0 mg/(kg x d) as well might cause
      or promote DNA damage, and a moderate amount such as 4.280 mg/(kg x d) could
      improve antioxidative and decrease DNA damage effectively.

PMID- 16111041
TI  - [Combination effects of vitamin A and zinc on human's PMBC DNA damage in vitro].
AB  - OBJECTIVE: To study the combination effects of vitamin A (Vit. A) and zinc on
      human's PBMC DNA damage in vitro. Methods The PBMC from healthy volunteer was
      purification and cultured in the basic culture medium with Vit.A of 10(-4), 10(
      5) and 10(-6) mol/L, or/and with Zn of 10(-6), 10(-5) 10(-4) and 10(-3) mol/L.
      The basic culture medium with K2Cr2O7 of 1 mmol/L was the male control. The
      damage of PBMC DNA was respectively examined by SCGE and the image analyzer
      measured the comet tail rate and length. The apoptosis of each group PBMC was
      detected by FCM. RESULTS: The overdose supplement of zinc and Vit. A can damage
      the PBMC DNA in vitro culture (P < 0.01), while the suitable supplement doesn't
      find. When the Vit. A supplement has been excessive, giving suitable zinc could
      repair the damage of DNA, but would expand the injured cell. While when the zinc
      supplement has been excessive, giving suitable Vit. A could protect the healthy
      cells, but would aggravate the damage degree of injured cell. CONCLUSION: In
      vitro culture, the overdose Vit. A and zinc supplement could damage the human's
      PBMC DNA significantly. This need more researches to provide.

PMID- 16111042
TI  - [Study on determination of polycholorinated biphenyls in fish by isotopedilution
      GC-LRMS].
AB  - OBJECTIVE: To develop a method for determination of 20 indicator polycholorinated
      biphenyls in fish by GC-LRMS. METHODS: Fish sample was added 13C lablled internal
      standard and cleaned-up by a multilayer silica column and a alumina column.
      Sample was analyzed by HRGC-LRMS using SIM mode. RESULTS: Detection limits of 20
      indicator polycholorinated biphenyls were 0.009 - 0.044 ng/g. Average recovery
      were 79.7% - 112.6%, RSD were 1% - 8% (n = 6). CONCLUSION: Results showed that
      the method was suitable for determination of indicator PCB in fish sample.

PMID- 16111043
TI  - [Research of the contents of in vitro protein in the seed of sck transgenic
      rice].
AB  - OBJECTIVE: To detect the expression level of CpTI and HPT proteins in the seed of
      sck transgenic rice. METHODS: The seeds of T6 sck transgenic rice were detected
      by PCR. The CpTI and HPT proteins in the seeds, stems, roots and leaves of
      positive plants were detected by Western blot. The CpTI and HPT proteins in the
      seeds of positive plants and the control plants were detected by double sandwich
      ELISA. RESULTS: hpt and sck genes were found in T6 sck rice. The CpTI and HPT
      proteins were positive in the leaves, stems, and roots in Western blot analysis,
      and negative in the seeds. The content of CpTI protein is lower than LLD of
      double sandwich ELISA (< 14 ug/L), and HPT protein could not be detected.
      CONCLUSION: The content of CpTI protein in the seeds of T6 sck rice is lower than
      LLD of double sandwich ELISA, and HPT protein could not be detected.

PMID- 16111044
TI  - [Effects of early weaning on the blood glucose, blood lipid and hormone of rat
      fed a high fat diet].
AB  - OBJECTIVE: To observe the effects of early weaning on the blood glucose, blood
      lipid and hormone of rat fed a high fat diet. METHODS: Male Wistar rats were
      randomly divided into two groups after born 17 days according to body weight. One
      group was early weaned in the 17th day, the other was breastfed until the 24th
      day. After 4 weeks fed with basic diet, 12 rats were randomly selected from each
      group and were sacrificed. The other rats of each group were further randomly
      divided into 2 groups according to body weight. One group was fed a high fat
      diet, the other was fed the basic diet. The rats were sacrificed respectively at
      the end of the experiment. The blood glucose, serum lipids, and hormones were
      measured. RESULTS: Compared with the normal weaning rats, the weight and fat pad
      of early weaning rats significantly increased and the level of blood glucose,
      serum lipids, insulin, leptin also increased significantly (P < 0.05), the level
      of HDL, FT3 decreased (P < 0.05). CONCLUSION: The tendency of obesity in early
      weaning rats were more obvious than normal weaning rats after fed a high fat
      diet.

PMID- 16111045
TI  - [Role of cyclooxygenase-2 in inhibition of human gastric adenocarcinoma cell line
      SGC-7901 by c9, t11-conjugated linoleic acid].
AB  - OBJECTIVE: To study the effects of c9, t11-conjugated linoleic acid (c9, t11-CLA)
      on the critical enzyme (COX-2) and its product - prostaglandin E2 (PGE2) of
      linoleic acid metabolism path in human gastric adenocarcinoma cell line (SGC
      7901). METHODS: Expression of COX-2 mRNA and protein were measured by reverse
      transcription polymerase chain reaction (RT-PCR) and Western blot, PGE2 was
      determined by radioimmunoassay (RIA). RESULTS: At the concentrations of 25, 50,
      100, 200 pmol/L, c9, t11-CLA suppressed the expression of COX-2 mRNA, protein and
      PGE. CONCLUSION: COX-2 is involved anti-cancer action of c9, t11-CLA and is
      likely to act as an important target.

PMID- 16111046
TI  - [Study on the inhibitory effects of juice of tomato on the growth of human
      prostate carcinoma PC-3 cells].
AB  - OBJECTIVE: To study on the inhibitory effects of juice of tomato on the growth of
      human prostate carcinoma PC-3 cells and its possible mechanism. METHODS: PC-3
      cells were treated with the juice of tomato in different concentration (40, 80,
      120 ul/ml) for 48h; the proliferation of PC-3 cells were measured by MTT assay,
      the comet assay was used to measure the DNA damage of PC-3 cells. RESULTS: Juice
      of tomato could inhibit the proliferation of PC-3 cells, the growth inhibitory
      rate of experimental groups were significantly higher than that of control group,
      with very statistical significance; and it could induce the breakage of DNA
      single strand of PC-3 cells and resulted in comet cells with tail, Rate of DNA
      tail and the tail length of DNA increased with the increasing of concentration of
      juice of tomato, showing the obvious dose effect relationship. CONCLUSION: Juice
      of tomato could lead to DNA damage of PC-3 cells, it was related to that could
      inhibit the proliferation of PC-3 cells.

PMID- 16111047
TI  - [Molecular analysis of Salmonella enteritidis by pulsed-field gel
      electrophoresis].
AB  - OBJECTIVE: To study the relationship between different strains of Salmonella
      enteritidis, a molecular epidemiologic analysis method-pulsed-field gel
      electrophoresis was established and Salmonella enteritidis isolated from food
      samples were tested. METHODS: Food samples were collected from Henan province,
      Heilongjiang province and other provinces in 1991 - 2001. Strains were isolated
      and single colony of each Salmonella enteritidis strain from an agar plate was
      picked and enriched, then the total DNA was extracted in turn with lysozyme
      solution, proteinase K solution and TE buffer. The agarose pulgs were digested
      with restriction enzyme XbaI overnight at 37 degrees C, followed by pulsed-field
      gel electrophoresis (PFGE) with a CHEF Mapper system in 0.5 x TBE buffer with
      recirculation at 14 degrees C . DNA macrorestriction fragments were resolved on
      1% agarose gels, pulse time were ramped from 5s to 45s during a 26h run at 6V/cm.
      A lambda ladder pulsed-field gel maker was used as a size standard. RESULTS: 30
      Salmonella enteritidis strains were identified in chicken, beef, cooked meat and
      vegetables. 18 strains were isolated from henna province. More of the stains (22
      strains) were isolated in 2001. Two distinct DNA fragment profiles, PFGE types A
      and B, were observed, representing 63.3% and 36.7% of the isolates respectively.
      Type A could be subdivided further into two subtypes. Subtype A1 represented the
      majority (78.9%) of type A strains and differed from subtype A2 in that the
      latter lacked a band in the 50kb region. There was no correlation between the
      strains profiles and their isolation time or region. However, all the strains
      isolated from the chicken were totally type A1, and showed certain
      epidemiological trend which can be studied in the future. CONCLUSION: The pulsed
      field gel electrophoresis is a good method to study the molecular epidemiological
      relationship between the different Salmonella enteritidis srtains.

PMID- 16111048
TI  - [Histogenesis of lung adenocarcinoma induced by oral adminstration of mycotoxins
      in mice].
AB  - OBJECTIVE: To study the histogenesis and the putative mechanisms of
      adenocarcinoma induced by AFG1 and ST in NIH mice. METHODS: Thirty-four cases of
      lung adenocarcinomas induced by AFG1 and ST in NIH mice were included in this
      study and 12 cases of normal lung tissues were used as control. The phenotype of
      the lung adenocarcinomas was determined by immunohistochemical expression of SP-C
      and CC-10 at protein level. The expression of P53, Ras P21 and PCNA was studied
      with immunohistochemical staining. RESULT: The positive expression of SP-C was
      found in all the lung adenocarcinomas, while no expression of CC-10 could be
      seen. The labelling index of PCNA in the adenocarcinomas were significantly
      higher than that of control (P < 0.01). No positive expression of mutant P53 and
      Ras at protein level could be found. CONCLUSION: The lung adenocarcinomas induced
      by the two mycotoxins in NIH mice arise from alveolar type II cells and no
      expression of mutant P53 and Ras at protein level was found in the lung
      adenocarcinomas.

PMID- 16111049
TI  - [Evaluation on glycine chelated iron (II) in improving nutritional anemia in
      rats].
AB  - OBJECTIVE: In order to evaluate the efficacy of glycine chelated iron (II) in
      improving nutritional anemia in rats. METHODS: After weaning wistar rats,
      weighing 50 - 60g, were fed the iron deficient diet for three weeks, whole blood
      was taken from rat's tail to measure Hb, then the rats were randomly divided into
      five groups by Hb, that is the control group fed with iron deficient diet, three
      groups fed the diets supplemented with different glycine chelated iron (II), and
      another group fed with the diet added with lactate iron. Each group was fed
      respective diets for four weeks and indicators related to iron-deficient
      nutritional anemia were evaluated. RESULTS: The addition of glycine chelated iron
      (II) did improve the growth and development of rats, increase the hemoglobin
      level and the iron retention in spleen, decrease free erythrocyte protoporphyrin
      (FEP) content in whole blood, and there was no significant difference between
      three supplemental groups with glycine chelated iron (II) and the group with
      lactate iron. CONCLUSION: glycine chelated iron (II) can be used as a reasonable
      iron supplement in improving iron-deficient nutritional anemia.

PMID- 16111050
TI  - [Study on undernutrition and overweight coexisting within the same household].
AB  - OBJECTIVE: To describe the phenomenon of undernutrition and overweight coexisting
      within the same household on the level of household among 9 provinces in 2000. To
      explore the likely factors related to the phenomenon. METHODS: This is a cross
      sectional study. All households were categorized as four types: undernutrition,
      overweight, undernutrition/overweight and normal. Multinomial logistic regression
      was used to test the statistical significance of the association of
      undernutrition/overweight with sociodemographic factors while controlling for
      confounders. RESULTS: In 9 provinces of China, 6.9% of all households were found
      to have undernutrition and overweight members within the same household. The
      undernutrition/overweight households were more likely to be urban residence, have
      a motor vehical,own a washing machine, household head have a low energy
      occupation and more likely to consume a higher percentage of energy from animal
      fat. There were no significant differences between undernutrition/overweight and
      overweight households. There were 34.9% undernutrition/overweight households of
      all undernutrition households and 13.2% of all overweight households. CONCLUSION:
      It's essential to explore the phenomenon. The results will suggest the nutrition
      intervention to consider both undernutrition and chronic disease.

PMID- 16111051
TI  - [Study on N-nitroso compound in food and its relevant risk factors for esophageal
      cancer].
AB  - OBJECTIVE: To study multiple risk factors of N-nitroso compounds (NOC) in high-
      and low-risk areas for esophageal cancer in southern China. METHOD: The samples
      of 24-hr diets and 12-hr overnight urine were collected from 120 male healthy
      subjects (35-64 years old) selected by a 3-stage random cluster sample procedure
      in each of the high-risk area (Nanao County) and low-risk area (Lufeng County)
      for esophageal cancer. The urinary samples were respectively collected from
      undosed subjects, subjects ingested 500 mg L-proline (together with 200 mg
      ascorbic acid ) and subjects ingested 500 mg proline. The levels of total NOC
      (TNOC), N-nitrosamino acids (NAAs), volatile N-nitroso compounds and reductive
      ascorbic acid (VC) in the samples were measured. By unconditional logistic
      stepwise regression model, we analyzed the association between the multiple
      factors of NOC and esophageal cancer mortality. The factors included the intake
      and excretion levels of various kinds of NOC, the ability of NAAs endogenous
      formation and its inhibition by VC, and nutrition status of VC in the body.
      RESULTS: The results of unconditional logistic stepwise regression showed that
      risk factors entered the model were diet TNOC content (OR 9.613, 95% CI 1.921
      48.115) and urinary NAAs level after ingested VC (OR 1.137, 95 % CI 1.001-1.298).
      CONCLUSION: The higher level of diet TNOC and the lower inhibition ability of NOC
      endogenous formation by VC were important risk factors on NOC etiology of
      esophageal cancer in southern China.

PMID- 16111052
TI  - [A Markov model to access long-term effects of rosiglitazone natrium on the
      treatment of type 2 diabetes].
AB  - OBJECTIVE: The aim of this study was to estimate the long-term treatment effects
      of Rosiglitazone-natrium in type 2 diabetes. METHODS: A Markov decision model was
      developed to predict, over 10 years, mortality with or without Rosiglitazone
      natrium treatment. RESULTS: During 10 years research, 14.2% patients developed to
      complications of type 2 diabetes mellitus, 3.8% patients should be dead in
      Rosiglitazone-natrium treatment group. 22.7% patients developed to complications
      of type 2 diabetes, 6.6% patients should be dead in non-Rosiglitazone-natrium
      treatment group. CONCLUSION: Markov decision model should be useful in accessing
      the long-term effects of drug treatment. Evidence on long-term benefit of
      Rosiglitazone-natrium could be of importance for future decision making.

PMID- 16111053
TI  - [The hypoglycemic effects of crude polysaccharides extract from Momordica
      charantia in mice].
AB  - OBJECTIVE: In order to study the hypoglycemic effects of crude polysaccharides
      extract from Momordica charantia in normal and diabetic mice. METHODS: Oral
      glucose tolerance test was carried out in 24 normal mice, CPS was orally
      administered in experiment group at 1 g/kg BW. 80 diabetic mice (type 1 and type
      2 diabetic model) were divided into two groups randomly, CPS was administered at
      ad lib and fasted condition in experiment group at 1 g/kg BW, blood glucose was
      measured at different time. RESULTS: In normal mice, after administered glucose
      (3g/kgBW) the blood glucose level of experiment group at 0.5, 1 h was
      significantly lower than that of control group (16.4% and 16.5% lower than
      control group respectively, P < 0.05 and P < 0.01). In diabetic mice, the fasted
      and ad lib blood glucose after administering CPS orally 2h, 4h were lower than
      that of control group (P < 0.05 and P < 0.01 respectively). CONCLUSION: CPS can
      improve OGTT in normal mice, and has significant hypoglycemic effect in two types
      diabetic mice.

PMID- 16111054
TI  - [Progression of study on the health effects of indoor biological contaminants].
AB  - The use of HVAC (the heating, ventilation and air conditioning) system which
      leads to the inadequate circulation of indoor air, together with the
      popularization of family pets, creates an appropriate environment for survival
      and reproduction of air-borne microbes. Microbes with their toxin and allergen in
      air often adhere to saliva and particular matters, landing to the ground or
      floating in air for long time. Potential adverse health consequences may be led
      to subjects exposed to the biological contaminants. In particular, the disorders
      from the respiratory and allergic response were often reported. The progresses of
      studies on the biological contaminants during recent ten years were reviewed in
      the paper.

PMID- 16111055
TI  - [Identification and quantitation of selenocompounds in environment and organism].
AB  - Identify and quantify of diversity of selenocompounds in environment and organism
      is necessary to further understand and fairly evaluate the effects of selenium in
      clinical chemistry, nutrition, toxicity, environment and ecology. For the
      purpose, many state-of-the-art of analytical techniques are applied with the
      particular emphasis on the effective isolation, high-sensitively element
      selective detection and the identification of the detected selenocompounds. Some
      practical and recently-developed methods, especially Se speciation by the
      combination of chromatography with mass spectrography, are here reviewed, which
      is of benefit to the deep researches on the selenium species in environmental
      samples and biomaterials.

PMID- 16111056
TI  - [Antagonistic action of selenium against the toxicity of lead].
AB  - Selenium can antagonize lead toxicity by preventing damage from oxygen free
      radicals or by forming lead-selenium complex. In this review, three parts are
      summarized to discuss the relationship between selenium and lead toxicity: (1)
      The possible mechanisms of selenium protect against the toxicity of lead. (2) The
      antagonistic action of selenium on lead toxicity. (3). Effect of selenium in
      different forms on the toxicity of lead.

PMID- 16111057
TI  - [Domoic acid and human health].
AB  - Domoic acid (DA), structurally related to glutamic and kainic acid, mainly
      generated by Pseudo nitzschia diatom. It often contaminates halobios such as fish
      and seashell and cause the Amnesic Shellfish Poisoning in human beings with the
      consumption of foods contaminated by DA. DA has been detected from seafoods
      worldwide. As the frequent occurrence of red tide and outbreak of human
      poisoning, more and more studies focus on DA, especially on its excitotoxicity.
      The producing alga, physico - chemical properties, natural contamination of
      seafoods, information on human poisoning, toxicity and analytical methods of DA
      are reviewed.

PMID- 16111058
TI  - What are the chances of your paper being published in palliative medicine? An
      update.

PMID- 16111059
TI  - Peer review in action: the contribution of referees to advancing reliable
      knowledge.

PMID- 16111060
TI  - Existential issues do not necessarily result in existential suffering: lessons
      from cancer patients in Israel.
AB  - Existential distress has been recognized as a source of suffering for oncology
      patients. This study focusses on existential issues and coping mechanisms of a
      unique culturally diverse Jewish/Middle Eastern oncology population. A
      qualitative assessment of 40 patients with advanced cancer was undertaken through
      an interview process addressing the following themes: autonomy, dignity/body
      image, social isolation, coping mechanisms, guilt/past disappointments, spiritual
      health, meaning, hope and death/dying. The findings of this study indicate that
      existential concerns are endemic in this patient population, but that significant
      distress is relatively uncommon. Early palliative measures, family support,
      effective coping strategies, and religious belief systems may influence the way
      patients with advanced cancer deal with existential concerns.

PMID- 16111061
TI  - Quality of life change and response shift in patients admitted to palliative care
      units: a pilot study.
AB  - This pilot study was carried out to determine to what extent patients admitted to
      palliative care units (PCUs) in The Netherlands maintained good levels of
      individual quality of life (QoL), and to what extent response shift - a measure
      of adaptation - influenced QoL at the end of life. Two components of response
      shift were measured: reconceptualization (exchanging important areas of life) and
      value change (changing the perceived importance of important areas of life).
      Twenty patients admitted to PCUs were interviewed at one week, three weeks, and
      five weeks after admission. Results show that individual QoL was high and
      remained stable over the three measurement points. The individual QoL of patients
      who did not reconceptualize or did not change values was higher than the
      individual QoL of patients who did. The current pilot data need to be
      corroborated with data from additional respondents.

PMID- 16111062
TI  - Renal dialysis abatement: lessons from a social study.
AB  - AIM: This study aimed to examine the reasons why some people chose to abate
      (i.e., stop or not start) renal dialysis, together with the personal and social
      impact of this decision on the person concerned, and/or their families. METHOD: A
      qualitative design based on the principles of Grounded Theory was employed. Semi
      structured interviews were conducted with sixteen patients and/or carers
      (depending on whether the patient was able to be interviewed) where the issue of
      dialysis abatement was being considered, or had recently been decided. RESULTS:
      Of 52 participants considered for entry into the study 41 were ineligible, with
      impaired cognition, rapid medical deterioration, and inability to speak
      sufficient English being the main reasons for exclusion. The desire not to burden
      others and the personal experience of a deteriorating quality of life were
      crucial elements in the decision to stop or decline dialysis. The problem of
      prognostic uncertainty and a sense of abandonment were also prominently
      expressed. CONCLUSIONS: From this small Australian sample, it appears that there
      would be considerable potential benefit from a more proactive and open approach
      to end-of-life issues, with incorporation of the clinical and health promoting
      principles of palliative care into renal dialysis practice. The high number of
      exclusions shows how sick and unstable this population of patients is, but the
      issue of data gathering from people whose main language is not English requires
      attention.

PMID- 16111063
TI  - The development of a questionnaire to assess the attitudes of older people to end
      of-life issues (AEOLI).
AB  - OBJECTIVES: To develop an end-of-life attitudes questionnaire for use in a large
      community-based sample of older people. DESIGN: Nominal groups and
      standardization of questions. PARTICIPANTS: Eighteen older people, ten academics
      and five specialist palliative care health professionals were involved in nominal
      groups. Thirty older people took part in initial pilot work and a further 50 were
      involved in reliability testing. RESULTS: A 27-item attitudes of older people to
      end-of-life issues (AEOLI) questionnaire. DISCUSSION: In modern times, death and
      dying predominantly occurs among older people and yet we know very little about
      older people's attitudes to end-of-life care. The AEOLI questionnaire can be used
      in large scale surveys to elicit attitudes on end-of life issues considered
      important by older people and health care professionals.

PMID- 16111064
TI  - Older adults' attitudes to death, palliative treatment and hospice care.
AB  - BACKGROUND: Cancer patients who receive care from specialist palliative care
      services in the UK are younger than those who do not receive this care. This may
      be explained by age-related differences in attitudes to end-of-life care.
      OBJECTIVE: To determine the relationship between age and i) attitudes to death
      and preparation for death; and ii) knowledge about, and attitudes to, cancer and
      palliative care. DESIGN: Interviews with older people, using a novel
      questionnaire developed using nominal groups. Main comparisons were made between
      people aged 55-74 with those aged 75 years and over. SETTING: General practices
      in London. SUBJECTS: 129 people aged 55-74 and 127 people aged 75 years or over
      on the lists of general practitioners. METHODS: A cross-sectional survey to
      determine knowledge and experience of hospice care; preparation for end-of-life;
      and attitudes to end-of-life issues. RESULTS: Participants were knowledgeable
      about specialist palliative care and almost half had some indirect contact with a
      hospice. People aged >74 were less likely than younger participants to want their
      doctor to end their life in a terminal illness. Although they believed death was
      easier to face for older people, they did not believe that younger people
      deserved more consideration than older people when dying, or that they should
      have priority for hospice care. Education, social class, hospice knowledge and
      anxiety about death had little influence on overall attitudes. CONCLUSIONS: The
      relative under-utilization of hospice and specialist palliative care services by
      older people with cancer in the UK cannot be explained by their attitudes to end
      of-life issues and palliative care.

PMID- 16111066
TI  - Systematic review of hypnotherapy for treating symptoms in terminally ill adult
      cancer patients.
AB  - The aim of this review was to find the evidence for or against the use of
      hypnotherapy in the treatment of symptoms in terminally ill adult cancer
      patients. The title and abstract were evaluated following a search through Index
      Medicus/MEDLINE, EMBASE, CINHAHL, CancerLit, AHMED, Psychinfo, CISCOM, Cochrane
      and DARE. Search terms included hypnotherapy, cancer, terminal care and
      palliative care. Inclusion criteria included systematic reviews, randomized
      controlled trials, observational and prospective studies, retrospective surveys,
      case studies and reports. A total of 27 papers were evaluated. Two reviewers
      assessed the studies, one extracted the relevant data and 10% were evaluated
      independently by a third reviewer. The 27 papers comprised a randomized
      controlled trial, an observational study, a retrospective questionnaire and 24
      case studies. Hypnotherapy was used to treat a variety of symptoms, including
      pain, anxiety and depression. The poor quality of the studies and heterogeneity
      of the study population limited further evaluation; further research is required
      to understand the role of hypnotherapy in managing symptoms.

PMID- 16111065
TI  - The Norwegian Doloplus-2, a tool for behavioural pain assessment: translation and
      pilot-validation in nursing home patients with cognitive impairment.
AB  - BACKGROUND: Pain assessment is challenging in cognitively impaired (CI) patients
      due to inadequate self-report skills and observational ratings are an
      alternative. The Doloplus-2 is developed for pain assessment in the CI and rates
      somatic, psychomotor and psychosocial behaviours as indicators of pain. AIMS: To
      translate the Doloplus-2 into Norwegian, to test the Doloplus-2 with regard to
      criterion validity and to obtain the administrators' evaluation of the clinical
      performance of the Doloplus-2. METHODS: Nurses at three nursing homes, in
      collaboration with two research assistants, administered the Doloplus-2 to 59
      patients with dementia. The results were compared against experienced clinicians'
      pain ratings. Regression analyses were performed to explore each different item's
      contribution to the total pain score. The administrators also completed a
      debriefing questionnaire. RESULTS: The instrument was translated according to
      international guidelines. Regression analyses demonstrate that the Doloplus-2
      score accounts for 62% (R2) of the expert score and that the four most
      informative items could explain 68% of the expert score. Analyses of the
      different Doloplus-2 items indicate that facial expressions explain most and
      social life least of the expert's pain ratings. The administrators reported that
      Doloplus-2 was helpful and easy to administer, but questioned the validity of the
      psychosocial domain. CONCLUSIONS: The Norwegian Doloplus-2 demonstrates
      satisfactory criterion validity and clinical value in this pilot study. However,
      the content of the instrument needs a general re-evaluation, especially with
      regard to the psychosocial items.

PMID- 16111067
TI  - Carotid stenting for impending carotid blowout: suitable supportive care for head
      and neck cancer patients?
AB  - BACKGROUND: Carotid blowout (CB) represents a dramatic end-of-life situation for
      palliative head and neck cancer patients, their relatives and caregivers.
      Recently, endovascular therapy has been proposed for head and neck surgical
      patients. Preliminary reports showed a better outcome with less morbidity
      compared to the previous treatment modalities. However, the specific use of such
      techniques for palliative head and neck cancer patients has not been previously
      described. METHOD: Retrospective review of two cases of head and neck cancer
      patients receiving palliative care, presenting with a CB, managed with
      endovascular stent placement. RESULTS: Bleeding was effectively stopped by the
      procedure in both cases. Both patients developed a post-procedure
      thromboembolism, which was immediately treated by appropriate anticoagulation
      therapy. Neurological symptoms resolved within 24 hours allowing rapid hospital
      discharge. One patient died at home seven months later. The second patient is
      alive five months after the procedure. No recurrence of CB occurred in either
      patient. CONCLUSIONS: Endovascular stent placement for CB allows a rapid arrest
      of bleeding and permits the use of anticoagulation therapy in order to avoid long
      term neurological injury. In our view, carotid stenting should be considered as
      valid supportive care for palliative head and neck patients presenting with a CB.

PMID- 16111068
TI  - A national survey of oncologist and chest physicians' attitudes towards empirical
      anti-oestrogen therapy, early pleurodesis and preference of sclerosing agent in
      malignant breast and ovarian pleural disease.

PMID- 16111069
TI  - Ionized calcium in isolation may not detect all cases of symptomatic
      hypercalcaemia.

PMID- 16111070
TI  - Hydration for myoclonus.

PMID- 16111071
TI  - Quality of care at the end of life: how far are we from reaching a comprehensive
      solution to the problem?

PMID- 16111072
TI  - Death in hospital for cancer patients: an indicator of quality of end-of-life
      care.

PMID- 16111074
TI  - GIS expands marketing vistas.

PMID- 16111073
TI  - Assistive technology improves lives of people with disabilities.

PMID- 16111075
TI  - 10 common myths about survey.

PMID- 16111076
TI  - New dementia care guidelines issued.

PMID- 16111077
TI  - CMS overhauls Medicare appeals.

PMID- 16111078
TI  - Medical liability bill passes House for third year in a row.

PMID- 16111079
TI  - Long-sought patient safety legislation becomes law.

PMID- 16111080
TI  - New DTC guidelines please drug companies, anger critics.

PMID- 16111081
TI  - Frist's stem cell research views draw praise, incite anger.

PMID- 16111082
TI  - Executive director's report.

PMID- 16111083
TI  - Consortium releases clinical practice guidelines for quality palliative care.

PMID- 16111084
TI  - Advance directive not being honored: what can I do? What should have been done?

PMID- 16111086
TI  - What if it's acute cholangitis?
AB  - Up to 9% of patients admitted to hospital with gallstone disease have acute
      cholangitis--an infection of the biliary tree. This potentially fatal condition
      is usually a result of bile duct obstruction, most often by gallstones. Here we
      review the diagnosis and subsequent management of patients with acute
      cholangitis.

PMID- 16111085
TI  - 5HT3-receptor antagonists as antiemetics in cancer.
AB  - Effective antiemetic therapy is crucial for patients undergoing chemotherapy or
      radiotherapy for cancer. Severe nausea and vomiting associated with such cancer
      treatment can lead to anxiety, anorexia, dehydration, electrolyte disturbance and
      renal failure, and may interrupt cancer therapy, demoralise patients or even
      cause them to abandon treatment. In 1992, we welcomed the introduction of
      ondansetron, the first selective serotonin type 3- (5HT3-) receptor antagonist
      marketed in the UK, as an important advance in preventing chemotherapy-induced
      nausea and vomiting. Several selective 5HT3-receptor antagonists are now
      licensed. They are widely prescribed to patients receiving cancer treatment, but
      not always appropriately. Here we review their optimal use.

PMID- 16111087
TI  - Kansas Comprehensive Cancer Control and Prevention Plan.

PMID- 16111088
TI  - Mechanisms of acinar cell injury in acute pancreatitis.
AB  - Acute pancreatitis has many causes, all leading to a common pathway of changes
      within the pancreatic acinar cell. Key amongst these changes is premature
      intracellular activation of digestive enzymes but this is also accompanied by the
      appearance of cytosolic vacuoles, co-localization of digestive and lysosomal
      enzymes, activation of NF-kappaB, and release of pro-inflammatory cytokines. The
      exact mechanism responsible for enzyme activation remains the subject of much
      research effort and not a little debate, however it is clear that all of these
      changes are triggered by an abnormal, sustained rise in cytosolic calcium
      concentration, which is itself dependent both on release of calcium from
      endoplasmic reticulum stores and uptake from the extracellular milieu. Activated
      enzymes are directly damaging to the acinar cell themselves, but recruitment of
      circulating neutrophils leads to further cellular damage. Cytokines and
      neutrophil activation are also responsible for the systemic inflammatory response
      typically seen in severe acute pancreatitis.

PMID- 16111089
TI  - Inflammatory response on the pancreatic acinar cell injury.
AB  - Acute pancreatitis is an inflammatory disorder, and inflammation not only affects
      the pathogenesis but also the course of the disease. Acinar cell injury early in
      acute pancreatitis leads to a local inflammatory reaction; if marked this leads
      to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to
      distant organ damage and multiple organ dysfunction syndrome (MODS). MODS
      associated with acute pancreatitis is the primary cause of morbidity and
      mortality in this condition. Recent studies by us and other investigators have
      established the critical role played by inflammatory mediators such as TNF-alpha,
      IL-1beta, IL-6, IL-8, CINC/GRO-alpha, MCP-1, PAF, IL-10, CD40L, C5a, ICAM-1, MIP1
      alpha, RANTES, substance P, and hydrogen sulfide in acute pancreatitis and the
      resultant MODS. This review intends to present an overview of the inflammatory
      response that takes place following pancreatic acinar cell injury.

PMID- 16111090
TI  - Genetics of pancreatitis.
AB  - There was some recent progress in the understanding of genetic risk factors in
      chronic pancreatitis. Due to this progress some of the traditional views of the
      subject will change. Today, genetic risk factors are attributed a much more
      important role that in the past. The frequency and strength of mutations were
      higher than expected. Strong variants were the rare autosomal-dominant mutations
      N29I and R122H of PRSS1 (cationic trypsinogen) and homozygous N34S of SPINK1
      (pancreatic secretory trypsin inhibitor). Other mutations (heterozygous N34S,
      CFTR) were of lower relevance but still mediate a higher risk than alcohol
      consumption. The course of genetically determined pancreatitis is rather mild. In
      the long term pancreas cancer was found in some patients but apart from non
      smoking no adequate prophylactic strategy is available up to now.

PMID- 16111091
TI  - Fibrogenesis in the pancreas after acinar cell injury.
AB  - Fibrosis within the pancreas is a key feature of chronic pancreatitis and
      pancreatic cancer. It has now been well demonstrated that following injury to
      acinar cells, pancreatic stellate cell activation, migration and proliferation is
      the key mediator of this process. Many cytokines and growth factors have been
      studied, particularly TGF-beta, which appears to be the major stimulus to
      fibrinogenesis. There is current interest in the mechanisms of phenotypic change
      between the active and quiescent forms, apoptosis and the signalling pathways
      that may be involved. The pancreatic stellate cell is likely to play an important
      role in maintaining the normal extracellular matrix; we speculate that the
      dysregulation of this process is an important factor in chronic pancreatitis.

PMID- 16111092
TI  - Reducing the incidence and severity of post ERCP pancreatitis.
AB  - Acute pancreatitis remains the commonest complication of ERCP (endoscopic
      retrograde cholangiopancreatography) with published incidence rates that have
      changed little over 30 years despite significant advances in endoscope and ERCP
      accessory technology and the introduction of structured ERCP training. Technique
      related risk factors for post ERCP pancreatitis have been recognised for many
      years and have been recently refined via large prospective audits. These studies
      have also revealed the importance of patient related factors and highlighted the
      high incidence of post ERCP pancreatitis in women being investigated for
      acalculus biliary pain or idiopathic recurrent acute pancreatitis. Sphincter of
      Oddi hypertension is often found to be present in this group of patients. Methods
      of preventing post ERCP pancreatitis have been sought for many years and numerous
      drugs have been tried using a variety of regimes with heterogeneous groups of
      patients. At present pancreatic duct stenting looks to be the most efficacious
      prophylactic method but is not for the beginner endoscopist. It is possible,
      however, by using a simple strategy to minimise the incidence of post ERCP
      pancreatitis and modulate its severity.

PMID- 16111093
TI  - Clinical value of severity markers in acute pancreatitis.
AB  - Acute pancreatitis is a common digestive disease of which the severity may vary
      from mild, edematous to severe, necrotizing disease. An improved outcome in the
      severe form of the disease is based on early identification of disease severity
      and subsequent focused management of these high-risk patients. However, the
      ability of clinicians to predict, upon presentation, which patient will have mild
      or severe acute pancreatitis is not accurate. Prospective systems using clinical
      criteria have been used to determine severity in patients with acute
      pancreatitis, such as the Ranson's prognostic signs, Glasgow score, and the acute
      physiology and chronic health evaluation II score (APACHE II). Their application
      in clinical practise has been limited by the time delay of at least 48 h to judge
      all parameters in the former two and by being cumbersome and time-consuming in
      the latter. Contrast-enhanced computed tomography is presently the most accurate
      non-invasive single method to evaluate the severity of acute pancreatitis. It
      cannot, however, be performed to all patients with acute pancreatitis. Therefore,
      considerable interest has grown in the development of reliable biochemical
      markers that reflect the severity of acute pancreatitis. In this article we
      critically appraise current and new severity markers of acute pancreatitis in
      their ability to distinguish between mild and severe disease and their clinical
      utility.

PMID- 16111094
TI  - Algorithm for the diagnosis and treatment of acute biliary pancreatitis.
AB  - Gallstones are the commonest cause of acute pancreatitis in developed countries.
      There is now a considerable evidence base consolidated by a series of systematic
      reviews, meta-analyses and guidelines that has established a clear algorithm for
      diagnosis and management. In the majority of patients the combination of
      ultrasonography and serum alanine transaminase > or = 60 iu/l < or = 48 hours of
      symptoms will identify gallstones as the cause. The simplest method of severity
      assessment is a high level of serum C-reactive protein (> 150 mg/l up to 72 hours
      after symptoms). In mild disease, all fit patients must undergo laparoscopic
      cholecystectomy with intraoperative cholangiography or if not fit for surgery
      then endoscopic sphincterotomy during the same admission to prevent further
      attacks. All patients with severe disease should undergo endoscopic
      sphincterotomy in less than 72 hours. Patients with > 30% necrosis should undergo
      fine needle aspiration for bacteriology. Necrosectomy is indicated for infected
      necrosis or sterile necrosis if there are persisting clinically significant
      symptoms. There is increasing evidence for the use of minimally invasive
      pancreatic necrosectomy. Enteral nutrition should be instituted whenever possible
      but antibiotics should be reserved for patients with proven sepsis. The presence
      of fungal infection requires active anti-fungal therapy. Patients with severe
      disease should undergo cholecystectomy at a later stage. Patients who have
      undergone necrosectomy require long-term follow-up because of delayed
      complications.

PMID- 16111095
TI  - Surgery in the treatment of acute pancreatitis--open pancreatic necrosectomy.
AB  - Management of acute necrotizing pancreatitis has changed significantly over the
      past years. Early management is non-surgically and solely supportive. Today, more
      patients survive the early phase of severe pancreatitis due to improvements of
      intensive-care-medicine. Pancreatic infection is the major risk factor with
      regard to morbidity and mortality in the late phase of severe acute pancreatitis.
      Whereas early surgery and surgery for sterile necrosis can only be recommended in
      selected cases, pancreatic infection is a well accepted indication for surgical
      treatment. Surgery should ideally be postponed until four weeks after the onset
      of symptoms as necrosis is well demarcated at that time. Four surgical techniques
      can be performed with comparable results regarding mortality: necrosectomy
      combined with (1) open packing, (2) planned staged relaparotomies with repeated
      lavage, (3) closed continuous lavage of the retroperitoneum, and (4) closed
      packing. However, closed continuous lavage of the retroperitoneum, and closed
      packing seem to be associated with a lower morbidity compared to the other two
      approaches. Advances in radiologic imaging, new developments of interventional
      radiology and other minimal access interventions have revolutionized the
      management of many surgical conditions over the past decades. However, minimal
      invasive surgery and interventional therapy for infected necrosis should be
      limited to specific indications in patients who are critically ill and otherwise
      unfit for conventional surgery. Open surgical debridement is the "gold standard"
      for treatment of infected pancreatic and peripancreatic necrosis.

PMID- 16111096
TI  - Surgery in the treatment of acute pancreatitis--minimal access pancreatic
      necrosectomy.
AB  - Between 5% and 10% of patients with acute pancreatitis will develop infected
      pancreatic necrosis. Traditional open surgery for this condition carries a
      mortality rate of up to 50%, and therefore a number of less invasive techniques
      have been developed, including radiological drainage and a minimal access
      retroperitoneal approach. No randomised controlled trials have been published
      which compare these techniques. Indications for minimal access surgery are the
      same as for open surgery, i.e. infected pancreatic necrosis or failure to improve
      with extensive sterile necrosis. Access is obtained to the pancreatic necrosis
      via the left loin and necrosectomy performed using an operating nephroscope, and
      this often requires several procedures to remove all necrotic tissue. The cavity
      is continuously irrigated on the ward in between procedures. The results of this
      approach are encouraging, with less systemic upset to the patient, a lower
      incidence of post-operative organ failure when compared with open surgery, and a
      reduced requirement for ITU support. There is also a trend towards a lower
      mortality rate, although this does not reach statistical significance on the data
      published so far. Current evidence suggests that a minimal access approach to
      pancreatic necrosis is feasible, well tolerated and beneficial for the patient
      when compared with open surgery.

PMID- 16111097
TI  - Endoscopic therapy for chronic pancreatitis.
AB  - When endoscopic therapy is used for the treatment of patients with painful
      chronic pancreatitis, extracorporeal shock wave lithotripsy (ESWL) can be
      proposed as a first-line approach when obstructive ductal stone(s) induce
      upstream dilation of the main pancreatic duct. Stone fragmentation by ESWL is
      followed by endoscopic ductal drainage using pancreatic sphincterotomy,
      fragmented stone(s) extraction, and pancreatic stenting in case of ductal
      stricture. After completion of endoscopic pancreatic ductal drainage, long-term
      clinical benefit can be expected for two thirds of the patients. Best clinical
      results are associated with absence or cessation of smoking and with early
      treatment in the course of chronic pancreatitis, while alcohol abuse increases
      the risks of diabetes, steatorrhea and mortality. The complications of chronic
      pancreatitis are mainly the development of pseudocyst secondary to the downstream
      ductal obstruction, and biliary obstruction caused by fibrotic changes in the
      head of the pancreas. Successful endoscopic pseudocyst drainage is currently
      obtained in most patients, and carries a low complication rate. Biliary stenting
      is a safe and effective technique for the short-term treatment of symptomatic
      bile duct stricture due to chronic pancreatitis, but permanent resolution is
      obtained in only 25% of cases. In conclusion, endoscopic management is now
      considered to be the preferred interventional treatment of chronic pancreatitis,
      for patients selected on the basis of the anatomical changes caused by the
      disease. This treatment is generally safe, minimally invasive, often effective
      for years, does not prevent further surgery, and can be repeated.

PMID- 16111098
TI  - Customized surgical strategy in chronic pancreatitis.
AB  - Despite major advances in the management of patients with chronic pancreatitis,
      yet the disease remains an enigmatic process of uncertain pathogenesis,
      unpredictable clinical course, and unclear treatment. In most of the cases
      intractable pain is the main indication for surgical intervention. Furthermore
      complications related to adjacent organs, endoscopically not permanently
      controlled pancreatic pseudocysts, ductal pathology, conservatively intractable
      internal pancreatic fistula or suspected malignancy also require surgery. The
      ideal surgical approach should address all these problems--tailoring the various
      therapeutic options to meet the individual patient's needs. In our opinion, the
      ideal procedure for chronic pancreatitis is the duodenum preserving pancreatic
      head resection in terms of an extended drainage procedure, were the extent of the
      pancreatic head resection may be tailored to the morphology of the pancreatic
      gland, thus allowing a tailored concept (to resect and/or drain as much as
      necessary but as little as possible). Looking at the present data, there is no
      need to transsect the pancreatic axis above the portal vein. If portal vein
      thrombosis is present, an extended drainage procedure is mandatory without
      transsection of the neck of the pancreas.

PMID- 16111099
TI  - The differentiation between pancreatic neoplastic cysts and pancreatic
      pseudocyst.
AB  - The number of small and often asymptomatic cystic lesions detected in pancreas
      has increased during the last decade. Historically the vast majority of the
      pancreatic cystic lesions were considered pseudocysts, but in recent series the
      incidence of various neoplastic cysts, such as intraductal papillary mucinous
      neoplasm, serous cystadenomas and cystic endocrine tumours, has increased. The
      possible malignant potential in these cystic neoplasms warrants careful
      diagnostic workup to choose the optimal treatment for each patient. Patient's
      age, symptoms and a possible history of acute or chronic pancreatitis with known
      aetiology together with high quality imaging studies are important in the
      differential diagnosis between pseudocysts and neoplastic cysts. Endoscopic
      ultrasound, cyst fluid analysis and positron emission tomography may be used in
      selected patients, but the accuracy of these methods needs further investigation.

PMID- 16111100
TI  - Treatment of pancreatic pseudocysts.
AB  - According to the Atlanta classification an acute pseudocyst is a collection of
      pancreatic juice enclosed by a wall of fibrous or granulation tissue, which
      arises as a consequence of acute pancreatitis or pancreatic trauma, whereas a
      chronic pseudocyst is a collection of pancreatic juice enclosed by a wall of
      fibrous or granulation tissue, which arises as a consequence of chronic
      pancreatitis and lack an antecedent episode of acute pancreatitis. It is
      generally agreed that acute and chronic pseudocysts have a different natural
      history, though many reports do not differentiate between pseudocysts that
      complicate acute pancreatitis and those that complicate chronic disease.
      Observation--"conservative treatment"--of a patient with a pseudocyst is
      preponderantly based on the knowledge that spontaneous resolution can occur. It
      must, however, be admitted that there is substantial risk of complications or
      even death; first of all due to bleeding. There are no randomized studies for the
      management protocols for pancreatic pseudocysts. Therefore, today we have to rely
      on best clinical practice, but still certain advice may be given. First of all it
      is important to differentiate acute from chronic pseudocysts for management, but
      at the same time not miss cystic neoplasias. Conservative treatment should always
      be considered the first option (pseudocysts should not be treated just because
      they are there). However, if intervention is needed, a procedure that is well
      known should always be considered first. The results of percutaneous or
      endoscopic drainage are probably more dependent on the experience of the
      interventionist than the choice of procedure and if surgery is needed, an intern
      anastomosis can hold sutures not until several weeks (if possible 6 weeks).

PMID- 16111101
TI  - [Initiate a national diabetes incidence registry! A report from the National
      Board of Health and Welfare points out the significance of the disease for public
      health].

PMID- 16111102
TI  - [Ingestion of caustic agents--esophagogastroscopy guides the therapy].

PMID- 16111103
TI  - [LD isoenzyme in uterine aspirates a potential marker of endometrial cancer.
      Investigation of postmenopausal bleeding can be simpler and cheaper].
AB  - In diagnosing endometrial carcinoma in women with postmenopausal bleeding
      analysis of lactate dehydrogenase, LD, isoenzymes in uterine aspirates appeared
      to have 100 percent sensitivity and negative predictive value combined with high
      specificity and positive predictive value. Determination of the LD-profile is
      suggested as a marker for endometrial carcinoma in women with postmenopausal
      bleeding. Transvaginal ultrasonography might be combined with determination of
      the LD-isoenzyme profile to secure the diagnosis of endometrial malignancy in
      order to minimize the use of other more invasive diagnostic methods.

PMID- 16111104
TI  - [Surname as a marker of ethnicity. A study from child health services shows that
      immigrant respective Swedish families seem to be isolated in different ways].
AB  - A practical method was tested for identifying ethnicity through family names in
      the absence of precise demographic information. In a questionnaire study of
      children covered by the Swedish child health services in some different counties,
      all potential participants (the children's mothers) were classified as "Swedish"
      or "non-Swedish" using family names. Inter-rater reliability was assessed by
      comparing the scores of two independent raters (Cohen's kappa: 0.89). Cases in
      which the raters did not agree were settled through discussion. The method's
      validity was roughly measured by comparing assigned classifications against
      ethnicity information provided by the 63.8 percent of the mothers who returned
      the questionnaire (1039 of 1628). Assigned and self-reported classifications were
      the same in 86.5 percent of the cases. Information from child health services
      about mothers who had agreed to participate in the study revealed health-related
      differences between those who returned the questionnaires and those who did not.
      The family name classification method indicated an ethnic selectivity in drop-out
      rates, which was helpful in interpreting these health differences.

PMID- 16111105
TI  - [Follow up of urinary bladder cancer--a task for the urology nurse?].
AB  - The introduction of the flexible cystoscope has simplified the examination for
      both the patient and the examiner. With an attached video camera to the
      cystoscope it showed that the assistent nurse fastly learned to interpret any
      finding in the bladder. In an article from England it was shown that a trained
      nurse cystoscopist had the same accuracy in detecting bladder tumors as a
      consultant urologist. The present study addresses the question if the same is
      valid in our department. After a period of training we started the study. 50
      consecutive patients with known bladder cancer were first examined by the nurse
      who recorded any relapses of bladder tumor. Then the urologist examined the
      bladder unaware of the nurse's finding. Any discrepancy was reexamined together.
      23 relapse cases of tumor were found, all which were diagnosed by the nurse. The
      urologist was un-able to detect 2 small grade 1 tumors. The result strengthened
      us to initiate a nurse-led follow up of patients with known bladder tumor. Until
      now about 100 cystoscopies have been done by a nurse with only good experience.

PMID- 16111106
TI  - [Abdominal tuberculosis--still a diagnostic challenge. Two case reports and a
      literature review].
AB  - Abdominal tuberculosis (TB) is unusual in Sweden today. This paper presents two
      patients born 1981 and 1975, one with perforated duodenal ulcer due to
      Helicobacter pylori and/or Mycobacterium tuberculosis. Acute operation with
      suture was done, signs of granulomatous inflammation revealed culture positive
      for TB. The other was operated with appendectomy; the pathology was TB in the
      mesenteries and outside the caecum. Antituberculosis chemotherapy was given in
      both cases and neither patient suffered any major problems. These two cases show
      how important it is for surgeons to be aware of TB nowadays, particularly in
      patients born outside Sweden or those undergoing immune therapy.

PMID- 16111107
TI  - [Interpretation of liver tests is decisive for the choice of examination in
      hepatocellular jaundice].
AB  - Patients with jaundice are looked after by many different specialists: general
      internists, general surgeons, specialists in infectious diseases and
      gastroenterologists. Overuse of radiological methods has been demonstrated
      recently in patients hospitalized for jaundice in Sweden probably due to a lack
      of experience in interpretation of pathological liver tests especially in
      patients with hepatocellularjaundice. Two cases of hepatocellular jaundice with a
      diagnosis of autoimmune hepatitis are described. This condition led in one case
      to severe liver failure and to severe jaundice in the other case. These cases
      illustrate the consequences of delayed diagnosis and lack of treatment early in
      the course of autoimmune hepatitis. Furthermore the common delay in contact with
      a liver transplant center in patients with severe liver failure is discussed. It
      is concluded that specialized units should investigate patients with jaundice and
      a medical gastroenterologist should be contacted early in the hospitalization of
      these patients.

PMID- 16111108
TI  - [Open access is not only a vision. The development towards free access to
      research results has already started].

PMID- 16111109
TI  - [Health services can't afford the ongoing discrimination of women].

PMID- 16111110
TI  - [Scientific career ladders of women and men--time for a new scrutiny].

PMID- 16111111
TI  - [Amiodarone-induced thyrotoxicosis--a predictable complication].

PMID- 16111112
TI  - [A contribution by the acting heads of child psychiatry supports an inhumane
      refugee policy].

PMID- 16111113
TI  - [How can we show our solidarity with the accused in Libya?].

PMID- 16111114
TI  - Assessing the repeatability and reproducibility of the Leg Score: a Dutch Claw
      Health Scoring System for dairy cattle.
AB  - The optimal moment for trimming the claws of all dairy cows in a herd was
      investigated by assessing the external rotation of the hind claws of individual
      cows relative to the spinal column. This leg score consisted of three independent
      descriptors: 1 (good/normal), 2 (moderately deviant), and 3 (severely deviant).
      This study assessed the repeatability and the reproducibility of the leg score
      system, and the consistency of the advice given subsequently about trimming of
      the hind claws of all cows in the herd. Repeatability was assessed for 52 cows
      that were scored twice on the same day by 11 observers; the kappa value ranged
      from 0.17 to 0.66 (mean: 0.36). The probability of the same result for both
      assessments ranged from 0.49 to 0.80 (mean: 0.61). Claw trimming was advised if
      at least 20% of the cows had a leg score of 3. On the basis of the scores, 3
      observers consistently advised trimming of the hind claws of all the cows in the
      herd, and 6 observers consistently advised against the need for trimming in the
      short term; 2 observers had an inconsistent advice. The reproducibility of the
      scoring system was assessed in two dairy herds (62 and 50 cows). Eight observers
      evaluated the leg score of the cows of both herds on the same day. The mean kappa
      value of the leg score for all pairs of different observers (A-B, A-C etcetera)
      was 0.24 [-0.08-0.49]. In conclusion, the leg score is not a reliable method for
      determining the optimal moment for claw trimming in dairy cattle. The reasons for
      the inconsistent observations require further investigation.

PMID- 16111115
TI  - [Diagnosis in heart and kidneys].

PMID- 16111116
TI  - ['Buta': is it or is it not allowed?].

PMID- 16111117
TI  - [WSAVA 2005, Mexico City: a report].

PMID- 16111118
TI  - [International symposium on Ectoparasites of Pets (ISEP) Hannover, 8-11, May
      2005].

PMID- 16111119
TI  - [Food disasters, risk communication and trust].

PMID- 16111120
TI  - [Veterinarian: a beautiful, but demanding job].

PMID- 16111121
TI  - [Etiology and therapy of coprophagia].

PMID- 16111122
TI  - Medical Practices Act: what you need to know.

PMID- 16111123
TI  - Branson offers laid-back setting for big-time educational sessions.
AB  - Technology can be credited for providing half of this year's subject matter for
      the Arkansas Medical Society Educational Program and Expo, while Pay for
      Performance and a "Perfect Storm" filled out the roster during the four-pony
      parade at The Medicine Show on May 7 in Branson, Mo. While earning continuing
      education credits, physicians in attendance learned more about the benefits of
      electronic health records and electronic prescribing while also getting an update
      on the pay-for-performance initiative and how tobacco use and physical inactivity
      affect public and fiscal health. The programs, which were part of the AMS' 129th
      Annual Session, were held at Chateau on the Lake atop a picturesque mountain
      overlooking Table Rock Lake. For those of you who weren't in attendance, here are
      some of the highlights.

PMID- 16111124
TI  - Medicare's 'appropriate care measures' raise quality expectations. Reporting of
      ACM's focus on overall care.

PMID- 16111125
TI  - Airborne emissions of mercury from municipal solid waste. I: new measurements
      from six operating landfills in Florida.
AB  - Mercury-bearing material enters municipal landfills from a wide array of sources,
      including fluorescent lights, batteries, electrical switches, thermometers, and
      general waste; however, the fate of mercury (Hg) in landfills has not been widely
      studied. Using automated flux chambers and downwind atmospheric sampling, we
      quantified the primary pathways of Hg vapor releases to the atmosphere at six
      municipal landfill operations in Florida. These pathways included landfill gas
      (LFG) releases from active vent systems, passive emissions from landfill surface
      covers, and emissions from daily activities at each working face (WF). We spiked
      the WF at two sites with known Hg sources; these were readily detected downwind,
      and were used to test our emission modeling approaches. Gaseous elemental mercury
      (Hg(O)) was released to the atmosphere at readily detectable rates from all
      sources measured; rates ranged from approximately 1-10 ng m(-2) hr(-1) over aged
      landfill cover, from approximately 8-20 mg/hr from LFG flares (LFG included Hg(O)
      at microg/m3 concentrations), and from approximately 200-400 mg/hr at the WF.
      These fluxes exceed our earlier published estimates. Attempts to identify
      specific Hg sources in excavated and sorted waste indicated few readily
      identifiable sources; because of effective mixing and diffusion of Hg(O), the
      entire waste mass acts as a source. We estimate that atmospheric Hg releases from
      municipal landfill operations in the state of Florida are on the order of 10-50
      kg/yr, substantially larger than our original estimates, but still a small
      fraction of current overall anthropogenic losses.

PMID- 16111126
TI  - Airborne emissions of mercury from municipal solid waste. II: potential losses of
      airborne mercury before landfill.
AB  - Waste distribution and compaction at the working face of municipal waste
      landfills releases mercury vapor (Hg(o)) to the atmosphere, as does the flaring
      of landfill gas. Waste storage and processing before its addition to the landfill
      also has the potential to release Hg(o) to the air if it is initially present or
      formed by chemical reduction of Hg(II) to Hg(o) within collected waste. We
      measured the release of Hg vapor to the atmosphere during dumpster and transfer
      station activities and waste storage before landfilling at a municipal landfill
      operation in central Florida. We also quantified the potential contribution of
      specific Hg-bearing wastes, including mercury (Hg) thermometers and fluorescent
      bulbs, and searched for primary Hg sources in sorted wastes at three different
      landfills. Surprisingly large fluxes were estimated for Hg losses at transfer
      facilities (approximately 100 mg/hr) and from dumpsters in the field
      (approximately 30 mg/hr for 1000 dumpsters), suggesting that Hg emissions
      occurring before landfilling may constitute a significant fraction of the total
      emission from the disposal/landfill cycle and a need for more measurements on
      these sources. Reducing conditions of landfill burial were obviously not needed
      to generate strong Hg(o) signals, indicating that much of the Hg was already
      present in a metallic (Hg(o)) form. Attempts to identify specific Hg sources in
      excavated and sorted waste indicated few readily identifiable sources; because of
      effective mixing and diffusion of Hg(o), the entire waste mass acts as a source.
      Broken fluorescent bulbs and thermometers in dumpsters emitted Hg(o) at 10 to
      >100 microg/hr and continued to act as near constant sources for several days.

PMID- 16111127
TI  - Biodegradation of trace gases in simulated landfill soil cover systems.
AB  - The attenuation of methane and seven volatile organic compounds (VOCs) was
      investigated in a dynamic methane and oxygen counter gradient system simulating a
      landfill soil cover. The VOCs investigated were: Tetrachloromethane (TeCM),
      trichloromethane (TCM), dichloromethane (DCM), trichloroethylene (TCE), vinyl
      chloride (VC), benzene, and toluene. Soil was sampled at Skellingsted landfill,
      Denmark. The soil columns showed a high capacity for methane oxidation, with
      oxidation rates up to 184 g/m2/d corresponding to a 77% reduction of inlet
      methane. Maximal methane oxidation occurred at 15-20 cm depth, in the upper part
      of the column where there were overlapping gradients of methane and oxygen. All
      the chlorinated hydrocarbons were degraded in the active soil columns with
      removal efficiencies higher than 57%. Soil gas concentration profiles indicated
      that the removal of the fully chlorinated compound TeCM was because of anaerobic
      degradation, whereas the degradation of lower chlorinated compounds like VC and
      DCM was located in the upper oxic part of the column. Benzene and toluene were
      also removed in the active column. This study demonstrates the complexity of
      landfill soil cover systems and shows that both anaerobic and aerobic bacteria
      may play an important role in reducing the emission of trace components into the
      atmosphere.

PMID- 16111128
TI  - Effect of flow distributors on uniformity of velocity profile in a baghouse.
AB  - In recent years, the utility industry has turned to baghouses as an alternative
      technology for particulate emission control from pulverized-coal-fired power
      plants. One of the more significant issues is to improve poor gas distribution
      that causes bag failures in baghouse operation. Bag failures during operation are
      almost impossible to prevent, but proper flow design can help in their
      prevention. This study investigated vertical velocity profiles below the bags in
      a baghouse (the hopper region) to determine whether flow could be improved with
      the installation of flow distributors in the hopper region. Three types of flow
      distributors were used to improve flow distribution and were compared with the
      original baghouse without flow distributors. Velocity profiles were measured by a
      hot-wire anemometer at an inlet velocity of 18 m/sec. Uniformity of flow
      distribution was calculated by the uniformity value U for the velocity profile of
      each flow distributor. Experimental results showed that the velocity profile of
      the empty configuration (without flow distributors) was poor because the
      uniformity value was 2.048. The uniformity values of type 1 (flow distributor
      with three vertical vanes), type 2 (flow distributor with one vertical and one
      inclined vane), and type 3 (flow distributor with two inclined vanes)
      configurations were reduced to 1.051, 0.617, and 0.526, respectively. These
      results indicate that the flow distributors designed in this study made
      significant improvements in the velocity profile of a baghouse, with the type 3
      configuration having the best performance.

PMID- 16111129
TI  - Temporal analysis of airborne particulate matter reveals a dose-rate effect on
      mortality in El Paso: indications of differential toxicity for different particle
      mixtures.
AB  - One of two topics explored is the limitations of the daily average in summarizing
      pollutant hourly profiles. The daily average of hourly measurements of air
      pollutant constituents provides continuity with previous studies using monitoring
      technology that only provided the daily average. However, other summary
      statistics are needed that make better use of all available information in 24-hr
      profiles. The daily average reflects the total daily dose, obscuring hourly
      resolution of the dose rate. Air pollutant exposures with comparable total daily
      doses may have very different effects when occurring at high levels over a few
      hours as opposed to low levels over a longer time. Alternative data-based choices
      for summary statistics are provided using principal component analysis to capture
      the exposure dose rate, while preserving ease of interpretation. This is
      demonstrated using the earliest hourly particle concentration data available for
      El Paso from archived records of particulate matter (PM)10. In this way, a
      significant association between evening PM10 exposures and nonaccidental daily
      mortality is found in El Paso from 1992 to 1995, otherwise missed using the daily
      average. Secondly, the nature and, hence, effects of particles in the ambient
      aerosol during El Paso sandstorms is believed different from that of particles
      present during still-air conditions resulting from atmospheric temperature
      inversions. To investigate this, wind speed (ws) is used as a surrogate variable
      to label PM10 exposures as Low-ws (primarily fine particles), High-ws (primarily
      coarse particles), or Mid-ws (a mixture of fine and coarse particles). A High-ws
      evening is significantly associated with a 10% lower risk of mortality on the
      succeeding third day, as compared with comparable exposures at Low- or Mid-ws.
      Although this analysis cannot be used to form firm conclusions because it uses a
      very small data set, it demonstrates the limitations of the daily average and
      suggests differential toxicity for different particle compositions.

PMID- 16111130
TI  - Comparison of two photochemical modeling systems in a tropical urban area.
AB  - Two photochemical smog modeling systems, UAM-V/ SAIMM (the Variable-Grid
      UAM/Systems Applications International Mesoscale Model) and CHIMERE/ECMWF
      (European Center for Medium Range Weather Forecast), are applied to the same
      tropical domain (Bangkok Metropolitan Region) and the same episode (January 13
      14, 1997) to evaluate their relative performance using the same anthropogenic
      emission database (emission database available at the Pollution Control
      Department [PCD] 1997). Ozone (O3) produced by both models meets U.S. Environment
      Protection Agency (EPA) suggested prediction criteria of mean normalized bias
      error and mean normalized gross error on January 14 but none on January 13. Both
      models are tested with various modified databases of precursors emissions from
      the PCD original database. Performance of UAM-V is the best when using the
      modified emission data with volatile organic compound (VOC), NOx, and CO mobile
      source emission reduced by 50%, 50%, and 20% from the original database. CHIMERE
      suggests a similar emission database except for the VOC emission, which is a
      reduction by 40% from the original PCD mobile source emission. Spatial and
      temporal variations of O3, CO, NOy (total reactive nitrogen), and Ox (NO2+O3)
      predicted by both model systems using the modified

PMID- 16111131
TI  - Decomposition of gas phase 1,3-butadiene by ultraviolet/ozone process.
AB  - A pilot-scale plug-flow reactor was built to investigate its performance in
      treating airborne 1,3-butadiene (BD) via ozonation (O3) and ultraviolet (UV)/O3
      technologies. Governing factors, such as the initial molar ratio of ozone to BD,
      UV volumetric electric input power, and moisture content in the influent
      airstream, were investigated. Experiments were conducted at an influent BD
      concentration of approximately 50 ppm, an ambient temperature of 26 degrees C,
      and a gas retention time of 85 sec. Results show that an initial molar ratio of
      ozone to BD of 3.5 and 2 sufficed to obtain BD decompositions of >90% for
      ozonation and UV/O3, respectively. The UV irradiance did not directly promote the
      decomposition of BD, rather, it played a role in promoting the production of
      secondary oxidants, such as hydroxyl radicals. Kinetic analyses indicate that
      both types of BD decomposition are peudo-first-order with respect to BD
      concentrations. Moisture content (relative humidity = 40-99%) and UV volumetric
      electric input power (0.147 and 0.294 W/L) are both factors that weakly affect
      the rate of BD decomposition. Economic evaluation factors, including both energy
      of ozone production and UV electric input power, were also estimated.

PMID- 16111132
TI  - Predicting extents of mercury oxidation in coal-derived flue gases.
AB  - The proposed mercury (Hg) oxidation mechanism consists of a 168-step gas phase
      mechanism that accounts for interaction among all important flue gas species and
      a heterogeneous oxidation mechanism on unburned carbon (UBC) particles, similar
      to established chemistry for dioxin production under comparable conditions. The
      mechanism was incorporated into a gas cleaning system simulator to predict the
      proportions of elemental and oxidized Hg species in the flue gases, given
      relevant coal properties (C/H/O/N/S/Cl/Hg), flue gas composition (O2, H2O, HCl),
      emissions (NO(X), SO(X), CO), the recovery of fly ash, fly ash loss-on-ignition
      (LOI), and a thermal history. Predictions are validated without parameter
      adjustments against datasets from lab-scale and from pilot-scale coal furnaces at
      1 and 29 MWt. Collectively, the evaluations cover 16 coals representing ranks
      from sub-bituminous through high-volatile bituminous, including cases with Cl2
      and CaCl2 injection. The predictions are, therefore, validated over virtually the
      entire domain of Cl-species concentrations and UBC levels of commercial interest.
      Additional predictions identify the most important operating conditions in the
      furnace and gas cleaning system, including stoichiometric ratio, NO(X), LOI, and
      residence time, as well as the most important coal properties, including coal-Cl.

PMID- 16111133
TI  - Impacts of biodiesel on pollutant emissions of a JP-8-fueled turbine engine.
AB  - The impacts of biodiesel on gaseous and particulate matter (PM) emissions of a JP
      8-fueled T63 engine were investigated. Jet fuel was blended with the soybean oil
      derived methyl ester biofuel at various concentrations and combusted in the
      turbine engine. The engine was operated at three power settings, namely ground
      idle, cruise, and takeoff power, to study the impact of the biodiesel at
      significantly different pressure and temperature conditions. Particulate
      emissions were characterized by measuring the particle number density (PND;
      particulate concentration), the particle size distribution, and the total
      particulate mass. PM samples were collected for offline analysis to obtain
      information about the effect of the biodiesel on the polycyclic aromatic
      hydrocarbon (PAH) content. In addition, temperature-programmed oxidation was
      performed on the collected soot samples to obtain information about the
      carbonaceous content (elemental or organic). Major and minor gaseous emissions
      were quantified using a total hydrocarbon analyzer, an oxygen analyzer, and a
      Fourier Transform IR analyzer. Test results showed the potential of biodiesel to
      reduce soot emissions in the jet-fueled turbine engine without negatively
      impacting the engine performance. These reductions, however, were observed only
      at the higher power settings with relatively high concentrations of biodiesel.
      Specifically, reductions of approximately 15% in the PND were observed at cruise
      and takeoff conditions with 20% biodiesel in the jet fuel. At the idle condition,
      slight increases in PND were observed; however, evidence shows this increase to
      be the result of condensed uncombusted biodiesel. Most of the gaseous emissions
      were unaffected under all of the conditions. The biodiesel was observed to have
      minimal effect on the formation of polycyclic aromatic hydrocarbons during this
      study. In addition to the combustion results, discussion of the physical and
      chemical characteristics of the blended fuels obtained using standard American
      Society for Testing and Materials (ASTM) fuel specifications methods are
      presented.

PMID- 16111134
TI  - Biofilter treatment of volatile organic compound emissions from reformulated
      paint: complex mixtures, intermittent operation, and startup.
AB  - Two biofilters were operated to treat a waste gas stream intended to simulate off
      gases generated during the manufacture of reformulated paint. The model waste gas
      stream consisted of a five-component solvent mixture containing acetone (450
      ppm(v)), methyl ethyl ketone (12 ppm(v)), toluene (29 ppm(v)), ethylbenzene (10
      ppm(v)), and p-xylene (10 ppm(v)). The two biofilters, identical in construction
      and packed with a polyurethane foam support medium, were inoculated with an
      enrichment culture derived from compost and then subjected to different loading
      conditions during the startup phase of operation. One biofilter was subjected to
      intermittent loading conditions with contaminants supplied only 8 hr/day to
      simulate loading conditions expected at facilities where manufacturing operations
      are discontinuous. The other biofilter was subjected to continuous contaminant
      loading during the initial start period, and then was switched to intermittent
      loading conditions. Experimental results demonstrate that both startup strategies
      can ultimately achieve high contaminant removal efficiency (>99%) at a target
      contaminant mass loading rate of 80.3 g m(-3) hr(-1) and an empty bed residence
      time of 59 sec. The biofilter subjected to intermittent loading conditions at
      startup, however, took considerably longer to reach high performance. In both
      biofilters, ketone components (acetone and methyl ethyl ketone) were, more
      rapidly degraded than aromatic hydrocarbons (toluene, ethylbenzene, and p
      xylene). Scanning electron microscopy and plate count data revealed that fungi,
      as well as bacteria, populated the biofilters.

PMID- 16111135
TI  - Evaluation of biopolymer-modified concrete systems for disposal of cathode ray
      tube glass.
AB  - Cathode ray tubes (CRTs) from computer monitors and television sets, which
      contain significantly high percentage of lead (Pb) by weight, represent an
      enormous and growing hazardous waste problem in the United States and worldwide.
      As a result, new technologies are needed to cope with current CRT waste stream
      and increased hazard and build new markets for its recycled components,
      developing commercially viable concrete composites, as well as minimizing CRT
      disposal problems. In this study, commercially available biopolymers, such as
      xanthan gum, guar gum, and chitosan, were used to encapsulate CRT glass waste,
      reducing the Pb leachability. The biopolymers utilized contain a number of useful
      functional groups, such as carboxyl (xanthan), hydroxyl (guar), and amino groups
      (chitosan), which play important roles in binding and stabilizing Pb onto
      concrete structures. The use of biopolymers in concrete systems can create a
      stable interpenetrating cross-linking composite that will last for many years.
      Results from these new composites show 30% higher compressive strength than
      standard concrete and a sharp decrease in lead leachability from several thousand
      milligrams per liter initially to an amount of three-tenths milligrams per liter
      or lower values (much lower than the U.S. Environment Protection Agency standard
      for hazardous waste of 5 mg/L by the toxicity characteristic leaching procedure
      test), and for some of the composites leachability is below even the standard for
      drinking water. This efficient and cost-effective CRT-biopolymer-concrete
      composite is a new class of biopolymer-modified material that can potentially
      perform a significant role in relieving the current CRT issue.

PMID- 16111136
TI  - The impact of wet flue gas desulfurization scrubbing on mercury emissions from
      coal-fired power stations.
AB  - This article introduces a predictive capability for Hg retention in any Ca-based
      wet flue gas desulfurization (FGD) scrubber, given mercury (Hg) speciation at the
      FGD inlet, the flue gas composition, and the sulphur dioxide (SO2) capture
      efficiency. A preliminary statistical analysis of data from 17 full-scale wet
      FGDs connects flue gas compositions, the extents of Hg oxidation at FGD inlets,
      and Hg retention efficiencies. These connections clearly signal that solution
      chemistry within the FGD determines Hg retention. A more thorough analysis based
      on thermochemical equilibrium yields highly accurate predictions for total Hg
      retention with no parameter adjustments. For the most reliable data, the
      predictions were within measurement uncertainties for both limestone and Mg/lime
      systems operating in both forced and natural oxidation mode. With the U.S.
      Environmental Protection Agency's (EPA) Information Collection Request (ICR)
      database, the quantitative performance was almost as good for the most modern
      FGDs, which probably conform to the very high SO2 absorption efficiencies assumed
      in the calculations. The large discrepancies for older FGDs are tentatively
      attributed to the unspecified SO2 capture efficiencies and operating temperatures
      and to the possible elimination of HCl in prescrubbers. The equilibrium
      calculations suggest that Hg retention is most sensitive to inlet HCl and O2
      levels and the FGD temperature; weakly dependent on SO2 capture efficiency; and
      insensitive to HgCl2, NO, CA:S ratio, slurry dilution level in limestone FGDs,
      and MgSO3 levels in Mg/lime systems. Consequently, systems with prescrubbers to
      eliminate HCl probably retain less Hg than fully integrated FGDs. The analysis
      also predicts re-emission of Hg(O) but only for inlet O2 levels that are much
      lower than those in full-scale FGDs.

PMID- 16111137
TI  - Measurement of fine particles in diesel emissions using a real-time aerosol
      monitor.
AB  - A real-time monitoring methodology to determine diesel fine particles in diesel
      emissions has been evaluated. The range of particle size captured by the monitor
      was approximately 0.1 microm to 1 microm. DustTrak real-time monitors were
      connected to the dilution tunnel of the vehicle exhaust to measure the emissions
      during the vehicle tests under both dynamic and steady-state driving conditions,
      and concentration data were recorded every 5 sec. Test variation of the real-time
      monitoring among different test days was similar to that measured by traditional
      filter-based gravimetric method, whereas the repeatability of the monitor data
      within the same-day tests was better than that of gravimetric method.
      Correlations between the two methods were established for different fuels tested
      on a single light duty vehicle. When the emissions from the reference fuel was
      used to convert the monitor's response to diesel fuels, the levels determined by
      the real-time monitor were consistent with those measured by gravimetric method
      among different fuels tested. Use of the real-time monitor could provide
      information on the levels of fine particles that is more relevant to the public
      health than the total particles.

PMID- 16111138
TI  - Characterization of carbonaceous species of ambient PM2.5 in Beijing, China.
AB  - One-week integrated fine particulate matter (i.e., particles <2.5 microm in
      diameter; PM2.5) samples were collected continuously with a low-flow rate sampler
      at a downtown site (Chegongzhuang) and a residential site (Tsinghua University)
      in Beijing between July 1999 and June 2000. The annual average concentrations of
      organic carbon (OC) and elemental carbon (EC) at the urban site were 23.9 and 8.8
      microg m(-3), much higher than those in some cities with serious air pollution.
      Similar weekly variations of OC and EC concentrations were found for the two
      sampling sites with higher concentrations in the winter and autumn. The highest
      weekly variations of OC and EC occurred in the winter, suggesting that combustion
      sources for space heating were important contributors to carbonaceous particles,
      along with a significant impact from variable meteorological conditions. High
      emissions coupled with unfavorable meteorological conditions led to the max
      weekly carbonaceous concentration the week of November 18-25, 1999. The weekly
      mass ratios of OC:EC ranged between 2 and 4 for most samples and averaged 2.9,
      probably suggesting that secondary OC (SOC) is present most weeks. The range of
      contemporary carbon fraction, based on the C14 analyses of eight samples
      collected in 2001, is 0.330-0.479. Estimated SOC accounted for approximately 38%
      of the total OC at the two sites. Average OC and EC concentrations at Tsinghua
      University were 25% and 18%, respectively, higher than those at Chegongzhuang,
      which could be attributed to different local emissions of primary carbonaceous
      particles and gaseous precursors of SOC, as well as different summer
      photochemical intensities between the two locations.

PMID- 16111139
TI  - The effect of diesel fuel sulfur content on particulate matter emissions for a
      nonroad diesel generator.
AB  - The effect of sulfur content on diesel particulate matter (DPM) emissions was
      studied using a diesel generator (Generac Model SD080, rated at 80 kW) as the
      emission source to simulate nonroad diesel emissions. A load simulator was used
      to apply loads to the generator at 0, 25, 50, and 75 kW, respectively. Three
      diesel fuels containing 500, 2100, and 3700 ppm sulfur by weight were selected as
      generator fuels. The U.S. Environmental Protection Agency sampling Method 5
      "Determination of Particulate Matter Emissions from Stationary Sources" together
      with Method 1A "Sample and Velocity Traverses for Stationary Sources with Small
      Stacks or Ducts" was adopted as a reference method for measurement of the exhaust
      gas flow rate and DPM mass concentration. The effects of various parameters on
      DPM concentration have been studied, such as fuel sulfur contents, engine loads,
      and fuel usage rates. The increase of average DPM concentrations from 3.9 mg/Nm3
      (n cubic meter) at 0 kW to 36.8 mg/Nm3 at 75 kW is strongly correlated with the
      increase of applied loads and sulfur content in the diesel fuel, whereas the fuel
      consumption rates are only a function of applied loads. An empirical correlation
      for estimating DPM concentration is obtained when fuel sulfur content and engine
      loads are known for these types of generators: Y = Zm(alphaX + beta), where Y is
      the DPM concentration, mg/m3, Z is the fuel sulfur content, ppm(w) (limited to
      500-3700 ppm(w)), X is the applied load, kW, m is the constant, 0.407, alpha and
      beta are the numerical coefficients, 0.0118 +/- 0.0028 (95% confidence interval)
      and 0.4535 +/- 0.1288 (95% confidence interval), respectively.

PMID- 16111140
TI  - The recovery of ammonia and hydrogen sulfide from ground-level area sources using
      dynamic isolation flux chambers: bench-scale studies.
AB  - Controlled bench-scale laboratory experiments were conducted to evaluate the
      recovery of ammonia (NH3) and hydrogen sulfide (H2S) from dynamic isolation flux
      chambers. H2S (80-4000 ppb) and NH3 (5000-40,000 ppb) samples were diffused
      through the flux chamber to simulate ground level area source emissions while
      measuring the inlet and outlet flux chamber concentrations simultaneously.
      Results showed that the recovery of H2S during a 30-min sampling time was almost
      complete for concentrations >2000 ppb. At the lowest concentration of 80 ppb,
      92.55% of the H2S could be recovered during the given sampling period. NH3
      emissions exhibited similar behavior between concentrations of 5000-40,000 ppb.
      Within the 30-min sampling period, 92.62% of the 5000-ppb NH3 sample could be
      recovered. Complete recovery was achieved for concentrations >40,000 ppb.
      Predictive equations were developed for gas adsorption. From these equations, the
      maximum difference between chamber inlet and outlet concentrations of NH3 or H2S
      was predicted to be 7.5% at the lowest concentration used for either gas. In the
      calculation of emission factors for NH3 and H2S, no adsorption correction factor
      is recommended for concentrations >37,500 ppb and 2100 ppb for NH3 and H2S,
      respectively. The reported differences in outlet and inlet concentration above
      these ranges are outside the fullscale sensitivity of the gas sensing equipment.
      The use of 46-90 m of Teflon tubing with the flux chambers has apparently no
      effect on gas adsorption, because recovery was completed almost instantaneously
      at the beginning of the tests.

PMID- 16111141
TI  - The Missoula Valley semivolatile and volatile organic compound study: seasonal
      average concentrations.
AB  - The city of Missoula is located in a high mountain valley (elevation 3200 ft.) in
      western Montana and contains one of the largest populations in the entire Rocky
      Mountain Region completely enclosed by mountains. During the 2000/2001 Missoula
      Valley Sampling Program, ambient levels of 61 semivolatile organic compounds
      (SVOCs) and 54 volatile organic compounds (VOCs) were originally quantified
      before refining the analytical program to 28 of the most prominent SVOCs and VOCs
      found in the Missoula Valley airshed. These compounds were measured over 24-hr
      periods at two locations throughout an entire year. This study provides the
      first, comprehensive appraisal of the levels of SVOCs and VOCs measured
      simultaneously throughout all four seasons at two locations in the Missoula
      Valley, including those levels measured during the 2000 Montana wildfire season.
      Generally, SVOC levels were comparable between both sides of the Missoula Valley.
      However, there were nearly double the amount of VOCs measured at the more urban
      Boyd Park site compared with the rural Frenchtown sampling site, a result of the
      greater number of automobiles on the eastern side of the Valley. SVOCs and VOCs
      were measured at their highest levels of the sampling program during the winter.
      Forest fire smoke samples collected during the summer of 2000 showed significant
      increases in SVOC phenolic compounds, including phenol, 2-methylphenol, 4
      methylphenol, and 2,4-dimethylphenol. Although there were modest increases in
      some of the other SVOCs and VOCs measured during the fire season, none of the
      increases were as dramatic as the phenolics.

PMID- 16111142
TI  - Precipitation in light extinction reconstruction.
AB  - The U.S. Environmental Protection Agency (EPA) published the Regional Haze Rule
      (RHR) in 1999. The RHR default goal is to reduce haze linearly to natural
      background in 2064 from the baseline period of 2000-2004. The EPA default method
      for estimating natural and baseline visibility uses the Interagency Monitoring of
      Protected Visual Environments (IMPROVE) formula. The IMPROVE formula predicts the
      light extinction coefficient from aerosol chemical concentrations measured by the
      IMPROVE network. The IMPROVE light scattering coefficient formula using data from
      1994-2002 underestimated the measured light scattering coefficient by 700 Mm(-1),
      on average, on days with precipitation. Also, precipitation occurred as often on
      the clearest as haziest days. This led to estimating the light extinction
      coefficient of precipitation, averaged over all days, as the light scattering
      coefficient on days with precipitation (700 Mm(-1)) multiplied by the percent of
      precipitation days in a year. This estimate added to the IMPROVE formula light
      extinction estimate gives a real world estimate of visibility for the 20%
      clearest, 20% haziest, and all days. For example, in 1993, the EPAs Report to
      Congress projected visibility in Class I areas would improve by 3 deciviews by
      2010 across the haziest portions of the eastern United States because of the 1990
      Clean Air Act Amendments. Omitted was the light extinction coefficient of
      precipitation. Adding in the estimated light extinction coefficient of
      precipitation, the estimated visibility improvement declines to <1 deciview.

PMID- 16111143
TI  - Integrated assessment modeling of atmospheric pollutants in the Southern
      Appalachian Mountains. Part I: hourly and seasonal ozone.
AB  - Recently, a comprehensive air quality modeling system was developed as part of
      the Southern Appalachians Mountains Initiative (SAMI) with the ability to
      simulate meteorology, emissions, ozone, size- and composition-resolved
      particulate matter, and pollutant deposition fluxes. As part of SAMI, the
      RAMS/EMS-95/URM-1ATM modeling system was used to evaluate potential emission
      control strategies to reduce atmospheric pollutant levels at Class I areas
      located in the Southern Appalachians Mountains. This article discusses the
      details of the ozone model performance and the methodology that was used to scale
      discrete episodic pollutant levels to seasonal and annual averages. The daily
      mean normalized bias and error for 1-hr and 8-hr ozone were within U.S.
      Environment Protection Agency guidance criteria for urban-scale modeling. The
      model typically showed a systematic overestimation for low ozone levels and an
      underestimation for high levels. Because SAMI was primarily interested in
      simulating the growing season ozone levels in Class I areas, daily and seasonal
      cumulative ozone exposure, as characterized by the W126 index, were also
      evaluated. The daily ozone W126 performance was not as good as the hourly ozone
      performance; however, the seasonal ozone W126 scaled up from daily values was
      within 17% of the observations at two typical Class I areas of the SAMI region.
      The overall ozone performance of the model was deemed acceptable for the purposes
      of SAMI's assessment.

PMID- 16111144
TI  - Effects of aerosol species on atmospheric visibility in Kaohsiung City, Taiwan.
AB  - Visibility data collected from Kaohsiung City, Taiwan, for the past two decades
      indicated that the air pollutants have significantly degraded visibility in
      recent years. During our study period, the seasonal mean visibilities in spring,
      summer, fall, and winter were only 5.4, 9.1, 8.2, and 3.4 km, respectively. To
      ascertain how urban aerosols influence the visibility, we conducted concurrent
      visibility monitoring and aerosol sampling in 1999 to identify the principal
      causes of visibility impairments in the region. In this study, ambient aerosols
      were sampled and analyzed for 11 constituents, including water-soluble ions and
      carbon materials, to investigate the chemical composition of Kaohsiung aerosols.
      Stepwise regression method was used to correlate the impact of aerosol species on
      visibility impairments. Both seasonal and diurnal variation patterns were found
      from the monitoring of visibility. Our results showed that light scattering was
      attributed primarily to aerosols with sizes that range from 0.26 to 0.90 pm,
      corresponding with the wavelength region of visible light, which accounted for
      approximately 72% of the light scattering coefficient. Sulfate was a dominant
      component that affected both the light scattering coefficient and the visibility
      in the region. On average, (NH4)2SO4, NH4NO3, total carbon, and fine particulate
      matter (PM2.5)-remainder contributed 53%, 17%, 16%, and 14% to total light
      scattering, respectively. An empirical regression model of visibility based on
      sulfate, elemental carbon, and humidity was developed, and the comparison
      indicated that visibility in an urban area could be properly simulated by the
      equation derived herein.

PMID- 16111146
TI  - Coalition aims to generate veterinary pathologists.

PMID- 16111145
TI  - Impact of free calcium oxide content of fly ash on dust and sulfur dioxide
      emissions in a lignite-fired power plant.
AB  - Emitted pollutants from the Agios Dimitrios lignite-fired power plant in northern
      Greece show a very strong linear correlation with the free calcium oxide content
      of the lignite ash. Dust (fly ash) emissions are positively correlated to free
      calcium oxide content, whereas sulfur dioxide (SO2) emissions are negatively
      correlated. As a result, at present, the Agios Dimitrios Power Plant operates
      very strictly within the legislative limits on atmospheric particulate emission.
      In the present study, the factors to be considered in assessing the impact of
      lignite combustion on the environment are presented and evaluated statistically.
      The ash appears to have a remarkable SO2 natural dry scrubbing capability when
      the free calcium oxide content ranges between 4 and 7%. Precipitator operating
      problems attributable to high ash resistivity can be overcome by injecting sulfur
      trioxide to reduce the ash resistivity, with, of course, a probable increase in
      operating costs.

PMID- 16111147
TI  - Expression of interleukin-10 and suppressor of cytokine signaling-3 associated
      with susceptibility of cattle to infection with Mycobacterium avium subsp
      paratuberculosis.
AB  - OBJECTIVE: To determine functional characteristics of monocytes obtained from
      cows with subclinical infection with Mycobacterium avium subsp paratuberculosis
      (MAP) that may have predisposed those cows to becoming infected with MAP SAMPLE
      POPULATION: Monocytes obtained from 5 uninfected cows and 5 cows subclinically
      infected with MAP in a herd with a high prevalence of paratuberculosis (ie,
      Johne's disease). PROCEDURES: Monocytes from uninfected and subclinically
      infected cows were incubated with MAP for 2, 6, 24, 72, or 96 hours. Variables
      measured included expression of tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-10, IL-12, transforming growth factor-beta, and suppressor of
      cytokine signaling-3 (SOCS-3); apoptosis of monocytes; acidification of
      phagosomes; and killing of MAP. RESULTS: Monocytes from infected cows had greater
      expression of IL-10 and SOCS-3 at 2 hours of coincubation with MAP and lower
      expression of TNF-alpha and IL-12 when results for all incubation times were
      combined. Monocytes from infected cows had a greater capacity to acidify
      phagosomes. No differences were observed in the rate of apoptosis or capacity of
      monocytes to kill MAP organisms. CONCLUSIONS AND CLINICAL RELEVANCE: Monocytes
      obtained from cows with subclinical infection with MAP had upregulated expression
      of IL-10 and SOCS-3 within the first 2 hours after exposure to MAP organisms.
      Although this did not inhibit acidification of phagosomes, apoptosis of
      monocytes, or attenuation of the capacity to kill MAP organisms, it may have
      attenuated the capacity of mononuclear phagocytes to initiate inflammatory and
      adaptive immune responses.

PMID- 16111148
TI  - Effects of drug treatment on inflammation and hyperreactivity of airways and on
      immune variables in cats with experimentally induced asthma.
AB  - OBJECTIVE: To compare the effects of an orally administered corticosteroid
      (prednisone), an inhaled corticosteroid (flunisolide), a leukotriene-receptor
      antagonist (zafirlukast), an antiserotonergic drug (cyproheptadine), and a
      control substance on the asthmatic phenotype in cats with experimentally induced
      asthma. ANIMALS: 6 cats with asthma experimentally induced by the use of Bermuda
      grass allergen (BGA). PROCEDURES: A randomized, crossover design was used to
      assess changes in the percentage of eosinophils in bronchoalveolar lavage fluid
      (BALF); airway hyperresponsiveness; blood lymphocyte phenotype determined by use
      of flow cytometry; and serum and BALF content of BGA-specific IgE, IgG, and IgA
      determined by use of ELISAs. RESULTS: Mean +/- SE eosinophil percentages in BALF
      when cats were administered prednisone (5.0 +/- 2.3%) and flunisolide (2.5 +/-
      1.7%) were significantly lower than for the control treatment (33.7 +/- 11.1%).
      We did not detect significant differences in airway hyperresponsiveness or
      lymphocyte surface markers among treatments. Content of BGA-specific IgE in serum
      was significantly lower when cats were treated with prednisone (25.5 +/- 5.4%),
      compared with values for the control treatment (63.6 +/- 12.9%); no other
      significant differences were observed in content of BGA-specific immunoglobulins
      among treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Orally administered and
      inhaled corticosteroids decreased eosinophilic inflammation in airways of cats
      with experimentally induced asthma. Only oral administration of prednisone
      decreased the content of BGA-specific IgE in serum; no other significant local or
      systemic immunologic effects were detected among treatments. Inhaled
      corticosteroids can be considered as an alternate method for decreasing airway
      inflammation in cats with asthma.

PMID- 16111149
TI  - Penetration of a topically applied nonsteroidal anti-inflammatory drug into local
      tissues and synovial fluid of dogs.
AB  - OBJECTIVE: To investigate penetration of a topically applied nonsteroidal anti
      inflammatory drug (NSAID) into tissues and synovial fluid. ANIMALS: 5 Greyhounds.
      PROCEDURE: Dogs were anesthetized and microdialysis probes placed in the dermis
      and gluteal muscle over each coxofemoral (hip) joint. Methylsalicylate (MeSA) was
      applied topically over the left hip joint. Dialysate and plasma (blood samples
      from the cephalic and femoral veins) were obtained during the subsequent 5 hours.
      Dogs were euthanatized, and tissue samples and synovial fluid were collected and
      analyzed for salicylic acid (SA) and MeSA by use of high-pressure liquid
      chromatography. RESULTS: SA and MeSA concentrations increased rapidly (< 30
      minutes after application) in dialysate obtained from treated dermis. Salicylic
      acid also appeared in plasma within 30 minutes and reached a plateau
      concentration after 2 hours, although combined drug concentrations (SA plus MeSA)
      in plasma obtained from femoral vein samples were twice those measured in plasma
      obtained from the cephalic vein (SA only). Treated muscle had a progressive
      decrease in NSAID concentration with increasing depth (SA and MeSA), but it was
      significantly higher than the concentration in untreated muscle. Substantial
      amounts of SA and MeSA were also measured in synovial fluid of treated joints.
      CONCLUSIONS AND CLINICAL RELEVANCE: Topically applied NSAIDs can penetrate deeply
      into tissues and synovial fluid. Local concentrations higher than circulating
      systemic concentrations are suggestive that direct diffusion and local blood
      redistribution are contributing to this effect. Systemic blood concentrations may
      be inadequate to describe regional kinetics of topically applied drugs.

PMID- 16111150
TI  - Effect of a silicone-containing dressing on exuberant granulation tissue
      formation and wound repair in horses.
AB  - OBJECTIVE: To determine the effect of a silicone dressing on the rate and quality
      of repair of limb wounds and compare microvascular occlusion and apoptosis in
      wounds treated with the silicone dressing and those treated with a conventional
      dressing in horses. ANIMALS: 5 horses. PROCEDURE: Horses received two 6.25-cm2
      wounds on each metacarpus. Ten wounds were treated with a silicone dressing; the
      other 10 were treated with a control dressing. Quality of repair and wound size
      were evaluated at each bandage change. Time to healing and the number of
      excisions of exuberant granulation tissue were recorded. Biopsy specimens taken
      from healed wounds were evaluated semiquantitatively via histologic examination,
      p53 immunohistochemical analysis, terminal deoxynucleotidyl transferase-mediated
      dUTP-biotin nick end labeling (TUNEL) to quantify apoptosis, and electron
      microscopic examination to measure microvessel luminal diameters. RESULTS: The
      silicone dressing surpassed the conventional dressing in preventing formation of
      exuberant granulation tissue and improving tissue quality. Microvessels were
      occluded significantly more often in wounds dressed with the silicone gel, which
      also diminished the expression of mutant p53, an indirect inhibitor of apoptosis,
      although greater apoptosis was not confirmed quantitatively by use of TUNEL.
      CONCLUSIONS AND CLINICAL RELEVANCE: Because the silicone dressing inhibited the
      formation of exuberant granulation tissue, it may be integrated in a management
      strategy designed to improve the repair of limb wounds in horses.

PMID- 16111151
TI  - Genomic expression patterns of cardiac tissues from dogs with dilated
      cardiomyopathy.
AB  - OBJECTIVE: To evaluate global genome expression patterns of left ventricular
      tissues from dogs with dilated cardiomyopathy (DCM). SAMPLE POPULATION: Tissues
      obtained from the left ventricle of 2 Doberman Pinschers with end-stage DCM and 5
      healthy control dogs. PROCEDURE: Transcriptional activities of 23,851 canine DNA
      sequences were determined by use of an oligonucleotide microarray. Genome
      expression patterns of DCM tissue were evaluated by measuring the relative amount
      of complementary RNA hybridization to the microarray probes and comparing it with
      gene expression for tissues from 5 healthy control dogs. RESULTS: 478 transcripts
      were differentially expressed (> or = 2.5-fold change). In DCM tissue, expression
      of 173 transcripts was upregulated and expression of 305 transcripts was
      downregulated, compared with expression for control tissues. Of the 478
      transcripts, 167 genes could be specifically identified. These genes were grouped
      into 1 of 8 categories on the basis of their primary physiologic function.
      Grouping revealed that pathways involving cellular energy production, signaling
      and communication, and cell structure were generally downregulated, whereas
      pathways involving cellular defense and stress responses were upregulated. Many
      previously unreported genes that may contribute to the pathophysiologic aspects
      of heart disease were identified. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation
      of global expression patterns provides a molecular portrait of heart failure,
      yields insights into the pathophysiologic aspects of DCM, and identifies
      intriguing genes and pathways for further study.

PMID- 16111152
TI  - Investigation of changes in the middle latency auditory evoked potential during
      anesthesia with sevoflurane in dogs.
AB  - OBJECTIVE: To investigate the middle latency auditory evoked potential (MLAEP) in
      awake dogs and dogs anesthetized with 2 concentrations of sevoflurane. ANIMALS:
      10 adult Beagles. PROCEDURE: The MLAEP was recorded while dogs were awake and
      anesthetized with sevoflurane (end-tidal concentration, 2.7% or 3.5%). Three
      needle electrodes were inserted SC, and click stimuli were delivered biaurally.
      Signal acquisition, averaging, and analysis were performed by use of computer
      software developed in-house. Signals were recorded for 128 milliseconds, and the
      responses to 1,024 stimuli were averaged. Waveforms from 10 recordings in each
      dog were averaged, and latencies of peaks were measured. Data acquired for awake
      dogs and dogs anesthetized with high and low sevoflurane concentrations were
      compared statistically. RESULTS: Sevoflurane anesthesia attenuated the MLAEP so
      that only peaks P0, Na, and Pa could be identified. The MLAEP changes were
      maximal at the lower concentration of sevoflurane evaluated. The latencies of
      these peaks were significantly shorter in awake dogs, compared with values in
      anesthetized dogs. No difference in the peak latency was detected between the
      sevoflurane concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: In terms of CNS
      responsiveness, the effects of anesthesia with sevoflurane are similar to those
      of anesthesia with isoflurane. Data suggest that sevoflurane is not the inhalant
      agent of choice in a research setting where electroencephalographic measurements
      are to be recorded during anesthesia. The depression of the MLAEP waveform by
      sevoflurane also suggests that the MLAEP is not a suitable tool with which to
      monitor anesthetic depth during sevoflurane anesthesia in dogs.

PMID- 16111153
TI  - Pharmacokinetics of lidocaine and its active metabolite,
      monoethylglycinexylidide, after intravenous administration of lidocaine to awake
      and isoflurane-anesthetized cats.
AB  - OBJECTIVE: To describe the pharmacokinetics of lidocaine and its active
      metabolite, monoethylglycinexylidide (MEGX), after i.v. administration of a
      single bolus of lidocaine in cats that were awake in phase 1 and anesthetized
      with isoflurane in phase 2 of the study. ANIMALS: 8 healthy adult cats.
      PROCEDURE: During phase 1, cats were administered lidocaine (2 mg/kg, i.v.) as a
      bolus injection (time 0). During phase 2, cats were anesthetized with isoflurane
      and maintained at 0.75 times the minimum alveolar concentration of isoflurane for
      each specific cat. After a 15-minute equilibration period, lidocaine (2 mg/kg,
      i.v.) was administered as a bolus injection to each cat (time 0). In both phases,
      plasma concentrations of lidocaine and MEGX were measured at various time points
      by use of liquid chromatography-mass spectrometry. RESULTS: Anesthesia with
      isoflurane significantly decreased the volume of the central compartment,
      clearance, and elimination half-life of lidocaine and significantly increased the
      extrapolated plasma drug concentration at time 0, compared with values for awake
      cats. Pharmacokinetics of MEGX were also changed by isoflurane-induced anesthesia
      because the maximum observed plasma concentration (C(max)), area under the
      concentration-time curve extrapolated to infinity, and time to C(max) were
      significantly higher in anesthetized cats, compared with values for awake cats.
      CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetics of lidocaine and MEGX were
      substantially altered in cats anesthetized by use of isoflurane. When
      pharmacokinetic variables are used to determine loading and infusion doses in
      awake or anesthetized cats, they should be measured in cats that are awake or
      anesthetized, respectively.

PMID- 16111154
TI  - Effects of tension of the girth strap on respiratory system mechanics in horses
      at rest and during hyperpnea induced by administration of lobeline hydrochloride.
AB  - OBJECTIVE: To determine whether tension of the girth strap of a saddle would
      sufficiently affect rib motion and reduce lung volume to alter pulmonary
      resistance in horses. ANIMALS: 10 healthy adult horses. PROCEDURE: We used
      classical techniques to measure the effects of tightening a girth strap (15 kg of
      tension) on pulmonary dynamics during eupnea and hyperpnea in horses. Respiratory
      impedance was evaluated by use of oscillometry, and resistance and reactance data
      were partitioned into lung and chest wall components. Rib cage and abdominal
      contributions to tidal volume and minute ventilation were measured by use of
      respiratory inductance plethysmography. Effects of strap tension on functional
      residual capacity (FRC) were measured during eupnea by use of a helium-dilution
      technique. In a subgroup of 6 horses, we also measured transdiaphragmatic
      pressures during eupnea and hyperpnea induced by administration of lobeline
      hydrochloride (0.2 mg/kg, i.v.). RESULTS: Pulmonary resistance measured by use of
      oscillometry but not by use of classical methods was significantly increased by
      the tension of the girth strap. However, the increase in pulmonary resistance
      could not be explained by a decrease in FRC. Motion of the rib cage was
      significantly reduced during eupnea and hyperpnea. However, ventilatory variables
      (tidal volume, minute ventilation, and peak flows), FRC, and transdiaphragmatic
      pressures were unaltered by strap tension. CONCLUSIONS AND CLINICAL RELEVANCE:
      Although tension of the girth strap caused measurable changes in respiratory
      mechanics (loss of rib motion and increased pulmonary resistance), there was no
      evidence that ventilation was limited.

PMID- 16111155
TI  - Influence of age, site, and degenerative state on the speed of sound in equine
      articular cartilage.
AB  - OBJECTIVE: To determine the speed of sound (SOS) in equine articular cartilage
      and investigate the influence of age, site in the joint, and cartilage
      degeneration on the SOS. SAMPLE POPULATION: Cartilage samples from 38
      metacarpophalangeal joints of 38 horses (age range, 5 months to 22 years).
      PROCEDURE: Osteochondral plugs were collected from 2 articular sites of the
      proximal phalanx after the degenerative state was characterized by use of the
      cartilage degeneration index (CDI) technique. The SOS was calculated (ratio of
      needle-probe cartilage thickness to time of flight of the ultrasound pulse), and
      relationships between SOS value and age, site, and cartilage degeneration were
      evaluated. An analytical model of cartilage indentation was used to evaluate the
      effect of variation in true SOS on the determination of cartilage thickness and
      dynamic modulus with the ultrasound indentation technique. RESULTS: The mean SOS
      for all samples was 1,696 +/- 126 m/s. Age, site, and cartilage degeneration had
      no significant influence on the SOS in cartilage. The analytical model revealed
      that use of the mean SOS of 1,696 m/s was associated with maximum errors of 17.5%
      on cartilage thickness and 70% on dynamic modulus in an SOS range that covered
      95% of the individual measurements. CONCLUSIONS AND CLINICAL RELEVANCE: In equine
      articular cartilage, use of mean SOS of 1,696 m/s in ultrasound indentation
      measurements introduces some inaccuracy on cartilage thickness determinations,
      but the dynamic modulus of cartilage can be estimated with acceptable accuracy in
      horses regardless of age, site in the joint, or stage of cartilage degeneration.

PMID- 16111156
TI  - In vitro cytopathic effects of a cysteine protease of Tritrichomonas foetus on
      cultured bovine uterine epithelial cells.
AB  - OBJECTIVE: To evaluate the cytopathic effects of Tritrichomonas foetus and a
      purified cysteine protease (ie, CP30) of T foetus on cultured bovine uterine
      epithelial cells (BUECs) in vitro. SAMPLE POPULATION: 10 reproductive tracts were
      obtained from late-term bovine fetuses at a commercial abattoir. PROCEDURE: An in
      vitro culture system of BUECs was developed to study the cytopathic effects of T
      foetus and purified CP30 of T foetus on host cells. Cytotoxicity of T foetus or
      CP30 on exposed BUECs was determined. Fluorescence microscopy and flow cytometry
      analyses were used to detect apoptosis. A fluorometric assay was used to detect
      BUEC caspase 3 activation. The CP inhibitor E-64 and a caspase inhibitor were
      used to inhibit apoptosis. RESULTS: Cytopathic effects were observed in BUECs
      treated with parasites or CP30 and were concentration and time dependent. The
      BUECs underwent apoptosis in the presence of parasites or CP30. The specific CP
      inhibitor E-64 abolished the induction of apoptosis in BUECs by CP30. The caspase
      inhibitor reduced the amount of apoptosis in BUECs. CONCLUSIONS AND CLINICAL
      RELEVANCE: T foetus and its CP30 induce apoptosis in cultured BUECs in vitro.
      Induction of apoptosis by CP30 is correlated with protease activity. Endometrial
      cell death as a result of a T foetus infection is likely to be more important in
      mediating infertility than a direct effect on the conceptus. Provoking an
      apoptotic reaction in the host may mitigate an inflammatory reaction or immune
      response and therefore favor survival of the parasite in a chronic infection.

PMID- 16111157
TI  - Effects of proinflammatory cytokines on canine articular chondrocytes in a three
      dimensional culture.
AB  - OBJECTIVE: To determine the effects of interleukin (IL)-1 and tumor necrosis
      factor (TNF)-alpha on canine chondrocytes cultured in an agarose-based 3
      dimensional (3-D) system. SAMPLE POPULATION: Humeral head articular cartilage
      chondrocytes obtained from 6 adult dogs. PROCEDURE: Chondrocytes were cultured in
      a 3-D system for < or = 12 days in serum-free medium with IL 1alpha, IL-1beta, or
      TNF-alpha at concentrations of 20, 50, or 100 ng/mL. After 1, 3, 6, and 12 days,
      glycosaminoglycan (GAG) concentrations in 3-D constructs; nitric oxide and
      prostaglandin E2 (PGE2) concentrations in media samples; and relative expressions
      of selected genes, including metalloproteinase (MMP)-13 and tissue inhibitor of
      metalloproteinase (TIMP)-1 and TIMP-2, were evaluated. Control specimens were
      comprised of chondrocytes cultured without proinflammatory cytokines. RESULTS: In
      control 3-D constructs, GAG content was significantly higher than for all other
      constructs. Compared with control values, relative expressions of MMP-13, TIMP-1,
      and TIMP-2 genes in the IL-1beta (50 ng/mL) group were significantly higher at
      day 1; at all evaluations, media concentrations of nitric oxide were
      significantly higher in all TNF-alpha-treated cultures; and concentrations of
      PGE2 in media samples were significantly higher in the IL-1beta (50 ng/mL) and IL
      1beta (100 ng/mL) groups at days 1 and 3, in the IL-1beta (100 ng/mL) group at
      day 6, and in all TNF-alpha groups at days 1, 3, and 6. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that TNF-alpha more readily induces production of
      nitric oxide and PGE2 by canine chondrocytes, compared with IL-1beta. In vitro,
      IL-1alpha appeared to have a minimal effect on canine chondrocytes.

PMID- 16111158
TI  - Effect of exercise on proglycogen and macroglycogen content in skeletal muscles
      of pigs with the Rendement Napole mutation.
AB  - OBJECTIVE: To investigate influence of the Rendement Napole (RN-) mutation on
      proglycogen (PG) and macroglycogen (MG) content in skeletal muscles before and
      after exercise and evaluate glycogen concentrations within various muscle fiber
      types. ANIMALS: 5 pigs with the RN- mutation and 3 noncarrier pigs. PROCEDURE:
      Pigs performed 2 exercise tests on a treadmill. In the first, pigs (mean body
      weight, 27 kg) ran a distance of approximately 800 m. In the second, pigs (mean
      body weight, 63 kg) ran until fatigued. Biopsy specimens (biceps femoris muscle)
      for determination of PG and MG contents were obtained before and after exercise,
      24 hours after the first test, and 3 hours after the second test. Histochemical
      analysis was performed on specimens obtained before and after the second test.
      RESULTS: Before exercise, PG stores did not differ markedly between groups, but
      MG stores were twice as high in pigs with the RN- mutation, compared with
      noncarrier pigs. The MG content decreased to a similar extent in both groups
      after exercise. Resynthesis of MG was greater in pigs with the RN- mutation than
      in noncarrier pigs by 3 hours after exercise. A low glycogen content after
      exercise was observed in many type I and type IIA fibers and in some type lIB
      fibers. CONCLUSIONS AND CLINICAL RELEVANCE: The RN- mutation was associated with
      high MG stores in skeletal muscle that did not influence exercise performance.
      The RN- mutation did not impair glycogenolysis during exercise but may induce
      faster resynthesis of MG after exercise.

PMID- 16111159
TI  - Characterization of the in vitro responses of equine cecal longitudinal smooth
      muscle to endothelin-1.
AB  - OBJECTIVE: To characterize the in vitro response of equine cecal longitudinal
      smooth muscle (CLSM) to endothelin (ET)-1 and assess the role of ETA and ETB
      receptors in those ET-1-induced responses. ANIMALS: 36 horses without
      gastrointestinal tract disease. PROCEDURE: To determine cumulative concentration
      response relationships, CLSM strips were suspended in tissue baths containing
      graded concentrations of ET-1 (10(-9) to 10(-6)M) with or without BQ-123 (ETA
      receptor antagonist); with or without IRL-1038 (ETB receptor antagonist); or with
      both antagonists at concentrations of 10(-9), 10(-7), and 10(-5)M. To determine
      the percentage change in baseline tension of CLSM, the areas under the curve
      during the 3-minute periods before and after addition of each dose were compared.
      Also, the effects of ET-1 and a combination of selective ETA and ETB receptor
      antagonists on electrically evoked contractions were studied. RESULTS: ET-1
      caused sustained increases in CLSM tension in a concentration-dependent manner.
      Contractile responses to ET-1 were not significantly inhibited by either BQ-123
      or IRL-1038 alone at any concentration; however, responses were significantly
      inhibited by exposure to the antagonists together at a concentration of 10(-5)M.
      Electrical field stimulation did not change the spontaneous contractile activity
      of CLSM and did not significantly alter the tissue response to ET-1, BQ-123, or
      IRL-1038. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that ET-1 has a
      contractile effect on equine CLSM that is mediated via ETA and ETB receptors. In
      vitro spontaneous contractions of equine CLSM apparently originate in the smooth
      muscle and not the enteric nervous system.

PMID- 16111160
TI  - Pharmacokinetic interactions of flunixin meglumine and enrofloxacin in dogs.
AB  - OBJECTIVE: To examine pharmacokinetic interactions of flunixin meglumine and
      enrofloxacin in dogs following simultaneously administered SC injections of these
      drugs. ANIMALS: 10 Beagles (4 males and 6 females). PROCEDURE: All dogs underwent
      the following 3 drug administration protocols with a 4-week washout period
      between treatments: flunixin administration alone (1 mg/kg, SC); simultaneous
      administration of flunixin (1 mg/kg, SC) and enrofloxacin (5 mg/kg, SC); and
      enrofloxacin administration alone (5 mg/kg, SC). Blood samples were collected
      from the cephalic vein at 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, and 24 hours
      following SC injections, and pharmacokinetic parameters of flunixin and
      enrofloxacin were calculated from plasma drug concentrations. RESULTS:
      Significant increases in the area under the curve (32%) and in the elimination
      half-life (29%) and a significant decrease (23%) in the elimination rate constant
      from the central compartment of flunixin were found following coadministration
      with enrofloxacin, compared with administration of flunixin alone. A significant
      increase (50%) in the elimination half-life and a significant decrease (21%) in
      the maximum plasma drug concentration of enrofloxacin were found following
      coadministration with flunixin, compared with administration of enrofloxacin
      alone. CONCLUSIONS AND CLINICAL RELEVANCE: The observed decrease in drug
      clearances as a result of coadministration of flunixin and enrofloxacin indicates
      that these drugs interact during the elimination phase. Consequently, care should
      be taken during the concomitant use of flunixin and enrofloxacin in dogs to avoid
      adverse drug reactions.

PMID- 16111161
TI  - Temporal folate status during lactation in mares and growth in foals.
AB  - OBJECTIVE: To identify changes in folate status of mares and foals during
      lactation and growth, respectively. ANIMALS: 20 Thoroughbred mares and foals.
      PROCEDURES: Pregnant mares, and following foaling the same mares with their
      foals, were maintained on mixed grass-legume pasture and fed either a traditional
      dietary supplement rich in sugar and starch (SS) or a dietary supplement high in
      fat and fiber (FF). Blood samples were collected monthly from mares and foals up
      to 6 months after foaling. Total folate concentration in feed and forage was
      determined. Analyses of plasma folate, RBC folate, plasma homocysteine (HCY), and
      milk folate concentrations were performed. RESULTS: Mare plasma folate
      concentrations declined moderately during 6 months of lactation. Mare RBC folate
      concentrations initially increased after foaling up to 3 months but declined
      toward the end of the study. Plasma HCY concentration was higher for mares fed
      the SS supplement, compared with mares fed the FF supplement from foaling to 6
      months of lactation. Milk folate concentrations decreased during the first 3
      months and then increased. Foal plasma folate initially declined but then
      increased. Stable concentrations of RBC folate were observed in foals. Plasma HCY
      concentrations in foals were unaffected by growth during the last 5 months.
      References range values for plasma folate, RBC folate, milk folate, and plasma
      HCY concentrations in healthy lactational mares and young growing foals were
      determined. CONCLUSIONS AND CLINICAL RELEVANCE: Folate status was not impaired in
      lactating mares and growing foals under the conditions in our study. It appears
      that folate supplementation is not necessary.

PMID- 16111162
TI  - Cardiopulmonary effects of fentanyl in conscious dogs and dogs sedated with a
      continuous rate infusion of medetomidine.
AB  - OBJECTIVE: To determine the hemodynamic consequences of the coadministration of a
      continuous rate infusion (CRI) of medetomidine with a fentanyl bolus in dogs.
      ANIMALS: 12 healthy sexually intact male dogs weighing 30.3 -/+ 4.2 kg (mean +/-
      SD). PROCEDURE: Dogs received either fentanyl alone (15.0 microg/kg, i.v. bolus)
      or the same dose of fentanyl during an 11-hour CRI of medetomidine (1.5
      microg/kg/h, i.v.). Prior to drug administration, dogs were instrumented for
      measurement of cardiac output, left atrial pressure, and systemic arterial blood
      pressures. Additionally, blood samples were collected from the pulmonary artery
      and left atrium for blood gas analysis. RESULTS: Medetomidine infusion reduced
      the cardiac index, heart rate, and O2, delivery while increasing left atrial
      pressure. Subsequent fentanyl administration further decreased the cardiac index.
      The Pao2 was not significantly different between the 2 treatment groups; however,
      fentanyl transiently decreased Pao2 from baseline values in dogs receiving a CRI
      of medetomidine. CONCLUSIONS AND CLINICAL RELEVANCE: Because of the prolonged
      hemodynamic changes associated with the CRI of medetomidine, its safety should be
      further evaluated before being clinically implemented in dogs.

PMID- 16111163
TI  - Evaluation of induction by use of a combination of oxymorphone and diazepam or
      hydromorphone and diazepam and maintenance of anesthesia by use of isoflurane in
      dogs with experimentally induced hypovolemia.
AB  - OBJECTIVE: To compare induction with hydromorphone and diazepam (HydroD) or
      oxymorphone and diazepam (OxyD) followed by maintenance with isoflurane in dogs
      with induced hypovolemia. ANIMALS: 6 healthy mixed-breed dogs. PROCEDURE: The
      study used a crossover design. Measurements were obtained in normovolemic dogs
      during isoflurane. Hypovolemia was induced (blood loss of 30 mL/kg) and
      measurements repeated following recovery from anesthesia, after HydroD
      (hydromorphone, 0.1 mg/kg; diazepam, 0.2 mg/kg; i.v.) or OxyD (oxymorphone, 0.05
      mg/kg; diazepam, 0.2 mg/kg; i.v.), after another dose of the same opioid, during
      administration of isoflurane (end-tidal concentration, 0.9%), and after
      glycopyrrolate (0.01 mg/kg, i.v.). Significant changes were identified. RESULTS:
      Induction effect was evident within 1 minute. All dogs were intubated after the
      second dose of opioid. No significant differences were found between inductions.
      The HydroD decreased heart rate (mean +/- SEM, -41 +/- 9.8 beats/min), whereas
      both inductions increased stroke index (0.4 +/- 0.09 mL/kg/beat) and caused
      moderate respiratory depression. Cardiac index was decreased (-30.2 +/- 6.04
      mL/kg/min) and there was minor metabolic acidosis during isoflurane following
      HydroD, compared with values for anesthetized normovolemic dogs. Glycopyrrolate
      increased heart rate (50 +/- 8.6 beats/min) and decreased systolic blood pressure
      (-23.2 +/- 4.87 mm Hg) in dogs induced with HydroD and decreased stroke index (
      0.3 +/- 0.08 mL/kg/beat) for both inductions. CONCLUSIONS AND CLINICAL RELEVANCE:
      Similar effects were detected after administration of HydroD or OxyD in
      hypovolemic dogs. Either combination should be safe for use in hypovolemic dogs.
      Administration of glycopyrrolate was not beneficial.

PMID- 16111164
TI  - Biochemical analysis of the articular cartilage and subchondral and trabecular
      bone of the metacarpophalangeal joint of horses with early osteoarthritis.
AB  - OBJECTIVE: To assess whether site-related changes in biochemical composition are
      present in the cartilage and subchondral and trabecular bone of the
      metacarpophalangeal joint of horses with early osteoarthritis. SAMPLE POPULATION:
      Right metacarpophalangeal joints from 59 mature warmblood horses. PROCEDURE:
      Biochemical data (cross-link, amino acid, DNA, and ash contents; denatured
      collagen and glycosaminoglycan [GAG] concentrations; bone mineral density; and
      mineral composition) were obtained from 2 differently loaded sites of phalanx I
      cartilage and subchondral and trabecular bone samples; data were compared with
      previously published values from nonosteoarthritic equine joints. RESULTS:
      Compared with findings in nonosteoarthritic joints, GAG concentration was lower
      in cartilage from osteoarthritic joints and there was a loss of site differences
      in cellularity and lysylpyridinoline (LP) cross-link content. In subchondral
      bone, LP cross-link content was decreased overall and there was a loss of site
      differences in osteoarthritic joints; ash content was higher in the
      osteoarthritic joints. Hydroxyproline content in trabecular bone from
      osteoarthritic joints was greater than that in nonosteoarthritic trabecular bone.
      In all 3 layers and at both sites, the linear increase of the pentosidine cross
      link content with age had diminished or was not apparent in the horses with
      osteoarthritic joints. CONCLUSIONS AND CLINICAL RELEVANCE: In equine
      metacarpophalangeal joints with early osteoarthritis, distinct biochemical
      changes were detected in the cartilage and subchondral and trabecular bone. The
      dissimilarity in response of the different tissues and differences between the
      sites that are affected may be related to differences in biomechanical loading
      and transmission and dissipation of force.

PMID- 16111165
TI  - Quantitative comparison of three commonly used treatments for navicular syndrome
      in horses.
AB  - OBJECTIVE: To quantitatively compare 3 commonly used treatments for navicular
      syndrome (NS) in horses: heel-elevation shoeing alone, heel-elevation shoeing and
      phenylbutazone administration, heel-elevation shoeing and injection of the distal
      interphalangeal joint (DIPJ) with triamcinolone acetonide (TA), and all 3
      treatments in combination. ANIMALS: 12 horses with NS. PROCEDURE: A force plate
      was used to measure baseline peak vertical ground reaction force (PVGRF) of the
      forelimbs. Each horse's forelimbs were shod with 3 degrees heel-elevation
      horseshoes; PVGRF was measured 24 hours and 14 days after shoeing. Fourteen days
      after shoeing (following data collection), phenylbutazone (4.4 mg/kg, i.v., q 12
      h) was administered (5 treatments). Two hours after the fifth treatment, PVGRF
      was measured; TA (6 mg) was injected into the DIPJ of the forelimb that generated
      the lower baseline PVGRF Fourteen days later, PVGRF was measured. Phenylbutazone
      was administered as before, and PVGRF was measured. Percentage body weight of
      force (%BWF) was calculated from PVGRF measurements and used for comparisons.
      RESULTS: 14 days after shoeing, mean %BWF in both forelimbs significantly
      increased from baseline; additional administration of phenylbutazone
      significantly increased %BWF applied from the more lame forelimb. Compared with
      shoeing alone, there was no significant change in %BWF after injection of the
      DIPJ with TA in shod horses. CONCLUSIONS AND CLINICAL RELEVANCE: Heel-elevation
      shoeing alone and in combination with phenylbutazone administration
      quantitatively decreased lameness in horses with NS. Although not significant,
      additional DIPJ injection with TA resulted in further quantitative decrease in
      lameness, compared with that achieved via shoeing alone.

PMID- 16111166
TI  - Effects of training on potassium homeostasis during exercise and skeletal muscle
      Na+,K(+)-ATPase concentration in young adult and middle-aged Dutch Warmblood
      horses.
AB  - OBJECTIVE: To investigate the effects of moderate short-term training on K+
      regulation in plasma and erythrocytes during exercise and on skeletal muscle
      Na+,K(+)-ATPase concentration in young adult and middle-aged horses. ANIMALS:
      Four 4- to 6-year-old and four 10- to 16-year-old Dutch Warmblood horses.
      PROCEDURE: The horses underwent a 6-minute exercise trial before and after 12
      days of training. Skeletal muscle Na+,K(+)-ATPase concentration was analyzed in
      gluteus medius and semitendinosus muscle specimens before and after the 12-day
      training period. Blood samples were collected before and immediately after the
      trials and at 3, 5, 7, and 10 minutes after cessation of exercise for assessment
      of several hematologic variables and analysis of plasma and whole-blood K+
      concentrations. RESULTS: After training, Na+,K(+)-ATPase concentration in the
      gluteus medius, but not semitendinosus, muscle of middle-aged horses increased
      (32%), compared with pretraining values; this did not affect the degree of
      hyperkalemia that developed during exercise. The development of hyperkalemia
      during exercise in young adult horses was blunted (albeit not significantly)
      without any change in the concentration of Na+,K(+)-ATPase in either of the
      muscles. After training, the erythrocyte K+ concentration increased (7% to 10%)
      significantly in both groups of horses but did not change during the exercise
      trials. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, the activation of skeletal
      muscle Na+,K(+)-ATPase during exercise is likely to decrease with age. Training
      appears to result in an increase in Na+,K(+)-ATPase activity in skeletal muscle
      with subsequent upregulation of Na+,K(+)-ATPase concentration if the existing
      Na+,K(+)-ATPase capacity cannot meet requirements.

PMID- 16111167
TI  - Effects of continuous low-dose infusion of lipopolysaccharide on expression of E
      selectin and intercellular adhesion molecule-1 messenger RNA and neutrophil
      accumulation in specific organs in dogs.
AB  - OBJECTIVE: To determine the effects of continuous low-dose infusion of
      lipopolysaccharide (LPS) on the expression of E-selectin and intercellular
      adhesion molecule-1 (ICAM-1) mRNA and neutrophil accumulation in the lungs,
      liver, spleen, small intestine, and pancreas in dogs. ANIMALS: 11 healthy adult
      Beagles. PROCEDURE: Dogs received a continuous infusion of a low dose (10
      microg/kg/h, i.v.) of LPS (Escherichia coli 055:B5) or saline (0.9% NaCI)
      solution (20 mL/kg/h, i.v.) for 8 hours. Activity levels of tumor necrosis factor
      alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (1L-6) and the
      number of WBCs in circulation were examined before and 1, 2, 4, and 8 hours after
      the onset of LPS infusion. Expression of E-selectin and ICAM-1 mRNA and the
      number of neutrophils in each tissue were examined. RESULTS: After the onset of
      LPS infusion, serum TNF-alpha and IL-1beta activities transiently increased.
      Thereafter, IL-6 activity increased, and high IL-6 activity was maintained
      throughout the experiment. In dogs in the LPS group, expression of E-selectin
      mRNA increased only in the lungs, and expression of ICAM-1 mRNA increased in the
      lungs and liver; the number of neutrophils in the tissue increased in the lungs
      and liver. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that expression
      of E-selectin and ICAM-1 mRNA increased during sepsis, particularly in the lungs
      and liver, and that this increase was associated with neutrophil accumulation.
      Hence, inhibiting the activation of endothelial cells in the lung and liver may
      decrease organ damage caused by accumulated neutrophils and help regulate
      multiple-organ dysfunction.

PMID- 16111168
TI  - Comparison of intraosseous and intravenous infusion of technetium Tc 99m
      pertechnate in the distal portion of forelimbs in standing horses by use of
      scintigraphic imaging.
AB  - OBJECTIVE: To describe and compare the distribution of technetium Tc 99m (99mTc)
      pertechnate following intraosseous or i.v. injection (with or without use of a
      tourniquet) in the distal portion of the forelimb in standing horses. ANIMALS: 4
      horses. PROCEDURE: Each horse received 4 forelimb treatments in random sequence:
      intraosseous infusion with tourniquet application (IOT), intraosseous infusion
      without tourniquet application, i.v infusion with tourniquet application (IVT),
      and i.v. infusion without tourniquet application. Dynamic nuclear scintigraphic
      imaging of the third metacarpal bone, proximal and middle phalanges, and distal
      phalanx was performed from the start of each treatment until 1 hour after
      infusion was completed. Radionuclide activity was compared within and between
      treatment groups. RESULTS: Tourniquet application was necessary to maintain high
      levels of radionuclide activity in the distal portion of the forelimb after
      intraosseous or i.v. infusion with 99mTc pertechnate; IVT and IOT treatments
      resulted in similar radionuclide activity in the proximal and middle phalanges
      and distal phalanx. Of the 4 treatments, there was significantly higher
      radionuclide activity in the distal aspect of the third metacarpal bone after the
      IOT treatment. CONCLUSIONS AND CLINICAL RELEVANCE: By use of a tourniquet,
      radionuclide administration via the intraosseous or i.v. routes resulted in
      effective perfusion of the distal portion of the forelimb and similar
      distribution of the agent in the phalanges of horses. Further studies are
      required to ascertain whether these findings apply to delivery of therapeutic
      agents in infected tissues via IOT or IVT.

PMID- 16111169
TI  - Comparison of measured oxyhemoglobin saturation and oxygen content with analyzer
      calculated values and hand-calculated values obtained in unsedated healthy dogs.
AB  - OBJECTIVE: To compare direct measurements of canine oxyhemoglobin (HbO2)
      saturation and blood oxygen content (ContO2) in healthy dogs with analyzer
      calculated values derived by use of a human HbO2 relationship and with hand
      calculated values derived by use of a canine HbO2 relationship. ANIMALS: 17
      healthy dogs. PROCEDURE: 3-mL samples of heparinized arterial and jugular venous
      blood were collected from each dog. The pH, Pco2, Po2, hemoglobin, HbO2,
      carboxyhemoglobin, methemoglobin, and ContO2 were measured; HbO2 and ContO2 were
      calculated automatically by analyzers and also hand-calculated. Blood gas
      analyzer-calculated and hand-calculated HbO2 values were compared with co
      oximeter-measured HbO2 values. Analyzer-calculated and hand-calculated ContO2
      values were compared with oxygen content analyzer-measured values. RESULTS: Hand
      calculated HbO2 values for arterial and jugular venous samples were slightly but
      significantly lower than those calculated by a blood gas analyzer or obtained
      from a co-oximeter. Hand-calculated and analyzer-calculated arterial and venous
      ContO2 were similar to measured values. CONCLUSIONS AND CLINICAL RELEVANCE:
      Although certain HbO2 and ContO2 values generated by use of the different methods
      were significantly different, these differences are unlikely to be clinically
      important in healthy dogs.

PMID- 16111170
TI  - In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in
      cats with lipopolysaccharide-induced pyrexia.
AB  - OBJECTIVE: To determine cyclooxygenase (COX)-2 selectivity, pharmacokinetic
      properties, and in vivo efficacy of firocoxib (ML-1,785,713) in cats. ANIMALS: 5
      healthy male and 14 healthy female domestic shorthair cats. PROCEDURE:
      Selectivity of firocoxib for inhibiting COX-2 was determined by comparing the
      potency for inhibiting COX-1 with that of COX-2 in feline blood. Pharmacokinetic
      properties were determined after i.v. (2 mg/kg) and oral (3 mg/kg) administration
      in male cats. In vivo efficacy was evaluated in female cats with
      lipopolysaccharide (LPS)-induced pyrexia with administration of firocoxib 1 or 14
      hours before LPS challenge. RESULTS: Blood concentrations resulting in 50%
      inhibition of COX-1 and COX-2 activity in vitro were 75 +/- 2 microM and 0.13 +/-
      0.03 microM, respectively, and selectivity for inhibiting COX-2 relative to COX-1
      was 58. Firocoxib had moderate to high oral bioavailability (54% to 70%), low
      plasma clearance (4.7 to 5.8 mL/min/kg), and an elimination half-life of 8.7 to
      12.2 hours. Firocoxib at doses from 0.75 to 3 mg/kg was efficacious in
      attenuating fever when administered to cats 1 or 14 hours before LPS challenge.
      CONCLUSIONS AND CLINICAL RELEVANCE: Firocoxib is a potent COX-2 inhibitor and is
      the only selective COX-2 inhibitor described for use in cats to date. It is
      effective in attenuating febrile responses in cats when administered 14 hours
      before LPS challenge, suggesting it would be suitable for once-a-day dosing.
      Because selective COX-2 inhibitors have an improved therapeutic index relative to
      nonselective nonsteroidal anti-inflammatory drugs in humans, firocoxib has the
      potential to be a safe, effective anti-inflammatory agent for cats.

PMID- 16111171
TI  - Use of simulation modeling to estimate herd-level sensitivity, specificity, and
      predictive values of diagnostic tests for detection of tuberculosis in cattle.
AB  - OBJECTIVE: To estimate herd-level sensitivity (HSe), specificity (HSp), and
      predictive values for a positive (HPVP) and negative (HPVN) test result for
      several testing scenarios for detection of tuberculosis in cattle by use of
      simulation modeling. SAMPLE POPULATION: Empirical distributions of all herds
      (15,468) and herds in a 10-county area (1,016) in Michigan. PROCEDURE: 5 test
      scenarios were simulated: scenario 1, serial interpretation of the caudal fold
      tuberculin (CFT) test and comparative cervical test (CCT); scenario 2, serial
      interpretation of the CFT test and CCT, microbial culture for mycobacteria, and
      polymerase chain reaction assay; scenario 3, same as scenario 2 but specificity
      was fixed at 1.0; and scenario 4, sensitivity was 0.9 (scenario 4a) or 0.95
      (scenario 4b), and specificity was fixed at 1.0. RESULTS: Estimates for HSe were
      reasonably high, ranging between 0.712 and 0.840. Estimates for HSp were low when
      specificity was not fixed at 1.0. Estimates of HPVP were low for scenarios 1 and
      2 (0.042 and 0.143, respectively) but increased to 1.0 when specificity was fixed
      at 1.0. The HPVN remained high for all 5 scenarios, ranging between 0.995 and
      0.997. As herd size increased, HSe increased and HSp and HPVP decreased. However,
      fixing specificity at 1.0 had only minor effects on HSp and HPVN, but HSe was low
      when the herd size was small. CONCLUSIONS AND CLINICAL RELEVANCE: Tests used for
      detecting cattle herds infected with tuberculosis work well on a herd basis.
      Herds with < approximately 100 cattle should be tested more frequently or for a
      longer duration than larger herds to ensure that these small herds are free of
      tuberculosis.

PMID- 16111172
TI  - [Editorial: Trends in clinical pathology].

PMID- 16111173
TI  - [Immunologic tests: Immunoglobulin G].

PMID- 16111174
TI  - [Immunologic tests: Immunoglobulin A].

PMID- 16111175
TI  - [Immunologic tests: Immunoglobulin M].

PMID- 16111176
TI  - [Immunologic tests: Immunoglobulin D].

PMID- 16111177
TI  - [Immunologic tests: Pyroglobulin, cryoglobulin].

PMID- 16111178
TI  - [Immunologic tests: Anti-immunoglobulin A antibody].

PMID- 16111179
TI  - [Diagnostic tests for causative allergens in vitro and in vivo].

PMID- 16111180
TI  - [Immunologic tests: Immunoglobulin E].

PMID- 16111182
TI  - [Immunologic tests: Antibody-dependent cell-mediated cytotoxicity (ADCC)].

PMID- 16111181
TI  - [Allergen-specific IgE antibody].

PMID- 16111183
TI  - [Histamine release test (HRT)].

PMID- 16111184
TI  - [Function of complement system and its role in biodefense].

PMID- 16111185
TI  - [Immunologic tests: CH50].

PMID- 16111186
TI  - [Immunologic tests: C1 (C1q, r, s)].

PMID- 16111187
TI  - [Immunologic tests: C1-inhibitor].

PMID- 16111188
TI  - [Immunologic tests: C2].

PMID- 16111189
TI  - [Immunologic tests: C3].

PMID- 16111190
TI  - [Immunologic tests: C3 receptor (CR1, 2)].

PMID- 16111191
TI  - [Immunologic tests: CR3 (Mac-1, CD11b/CD18), CR4 (CD11c/CD18)].

PMID- 16111192
TI  - [Immunologic tests: Factor B, factor D].

PMID- 16111194
TI  - [Immunological tests: Anaphylatoxins C3a, C4a, C5a].

PMID- 16111193
TI  - [Immunologic tests: Properdin, factor H, factor I].

PMID- 16111195
TI  - [Immunologic tests: C4].

PMID- 16111196
TI  - [Immunologic tests: C5].

PMID- 16111197
TI  - [Immunologic tests: C6, C7, C8 and C9].

PMID- 16111198
TI  - [Immunologic tests: Membrane cofactor protein (MCP, CD46)].

PMID- 16111199
TI  - [Immunological tests: Decay-accelerating factor].

PMID- 16111200
TI  - [Immunologic tests: Opsonin].

PMID- 16111201
TI  - [Immunologic tests: Circulating immune complex].

PMID- 16111202
TI  - [Immunologic tests: C1q-bound immune complex].

PMID- 16111203
TI  - [Immunological tests: Anti-C1q antibody].

PMID- 16111204
TI  - [Immunologic tests: C3d-bound immune complex].

PMID- 16111205
TI  - [Conglutinin binding test].

PMID- 16111206
TI  - [Polyethylene glycol complement consumption test (PEG -CC)].

PMID- 16111207
TI  - [Immunologic tests: Monoclonal RF immune complex].

PMID- 16111208
TI  - [Serological diagnosis of streptococcal infection (ASO, ASK, ADN-B, AHD, ASP)].

PMID- 16111209
TI  - [Cold agglutinin titration].

PMID- 16111210
TI  - [Tests for syphilis].

PMID- 16111211
TI  - [Widal test].

PMID- 16111212
TI  - [Weil-Felix test].

PMID- 16111213
TI  - [Immunologic tests: Urinary Haemophilus influenzae type-b antigen].

PMID- 16111214
TI  - [Immunodiagnosis of mycobacterial infection].

PMID- 16111215
TI  - [Diagnostic tests: Mycobacterium leprae].

PMID- 16111216
TI  - [Pneumococcal antigen tests].

PMID- 16111217
TI  - [Diagnostic tests: Neisseria gonorrhoeae].

PMID- 16111218
TI  - [Immunological tests: Corynebacterium diphtheriae, dephtheria toxin].

PMID- 16111219
TI  - [Campylobacter (Detection and identification of Campylobacter species)].

PMID- 16111220
TI  - [Helicobacter pylori IgG antibody, urea breath test, Helicobacter pylori antigen
      in the stool].

PMID- 16111221
TI  - [Diagnostic tests: Bordetella pertussis].

PMID- 16111222
TI  - [Immunologic tests: Legionella spp].

PMID- 16111223
TI  - [Diagnosis of typhoid fever and paratyphoid fever by serological and genetical
      methods].

PMID- 16111224
TI  - [Immunologic tests: Escherichia coli O157].

PMID- 16111225
TI  - [Immunological tests: Escherichia coli verotoxin].

PMID- 16111226
TI  - [Diagnostic tests: Endotoxin (lipopolysaccharide: LPS)].

PMID- 16111227
TI  - [Diagnostic tests: Bacterial protein toxins].

PMID- 16111228
TI  - [Immunologic tests: Clostridium tetani].

PMID- 16111229
TI  - [Diagnostic tests: Clostridium difficile].

PMID- 16111230
TI  - [Diagnostic tests: Leptospira].

PMID- 16111231
TI  - [Diagnostic tests: Lyme disease borrella].

PMID- 16111232
TI  - [Diagnostic tests: Chlamydia trachomatis, Chlamydophila pneumoniae].

PMID- 16111233
TI  - [Diagnostic tests: Mycoplasma pneumoniae].

PMID- 16111234
TI  - [Tsutsugamushi disease rickettsia].

PMID- 16111235
TI  - [Diagnostic tests: Japanese spotted fever].

PMID- 16111236
TI  - [Diagnostic tests: Cat-scratch disease].

PMID- 16111237
TI  - [Diagnostic tests: Candidiasis (candidosis)].

PMID- 16111238
TI  - [Diagnostic tests: Beta-D-glucan].

PMID- 16111239
TI  - [Diagnostic tests: Chlamydophila psittaci].

PMID- 16111240
TI  - [Diagnostic tests: Q fever].

PMID- 16111241
TI  - [Diagnostic tests: Tularemia].

PMID- 16111242
TI  - [Immunologic tests: Cryptosporidium].

PMID- 16111243
TI  - [Diagnostic tests: Coccidioidomycosis and paracoccidioidomycosis].

PMID- 16111244
TI  - [Immunologic tests: Cryptococcosis].

PMID- 16111245
TI  - [Immunologic tests: Histoplasma capsulatum var. capsulatum].

PMID- 16111246
TI  - [Diagnostic tests: Aspergillosis].

PMID- 16111247
TI  - [Immunologic tests: Toxoplasma].

PMID- 16111248
TI  - [Diagnostic tests: Entamoeba histolytica].

PMID- 16111249
TI  - [Immunologic tests: Echinococcosis].

PMID- 16111250
TI  - [Diagnostic tests: Filaria].

PMID- 16111251
TI  - [Immunodiagnosis of anisakidosis].

PMID- 16111252
TI  - [Paul-Bunnell test, Davidsohn differential test].

PMID- 16111253
TI  - [Diagnostic tests: Herpes simplex virus type 1 and 2].

PMID- 16111254
TI  - [Diagnostic tests: Varicella-zoster virus].

PMID- 16111255
TI  - [Diagnostic tests: Cytomegalovirus].

PMID- 16111256
TI  - [Immunologic tests: Epstein-Barr virus].

PMID- 16111257
TI  - [Diagnostic tests: Monkey pox].

PMID- 16111258
TI  - [Diagnostic tests: Human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7)].

PMID- 16111259
TI  - [Diagnostic tests: Adenovirus].

PMID- 16111260
TI  - [Diagnostic tests: Dengue virus].

PMID- 16111261
TI  - [Diagnostic tests: Hantavirus].

PMID- 16111262
TI  - [Diagnostic tests: West Nile virus].

PMID- 16111263
TI  - [Diagnostic tests: Nipah virus (NiV)].

PMID- 16111264
TI  - [Immunological tests: Antibodies to human papillomavirus type 16 L1-capsids].

PMID- 16111265
TI  - [Diagnostic tests: Human parvovirus B19].

PMID- 16111266
TI  - [Diagnostic tests: Norovirus].

PMID- 16111268
TI  - [Diagnostic tests: Corona virus].

PMID- 16111267
TI  - [Diagnostic tests: Japanese encephalitis virus and the other flavivirus].

PMID- 16111269
TI  - [Diagnostic tests: SARS-Corona virus].

PMID- 16111270
TI  - [Diagnostic tests: Influenza A, B, C viruses].

PMID- 16111271
TI  - [Diagnostic tests: Parainfluenza virus 1, 2, 3, 4].

PMID- 16111272
TI  - [Diagnostic tests: Mumps virus].

PMID- 16111273
TI  - [Diagnostic tests: Rubella virus].

PMID- 16111274
TI  - [Immunologic tests: Measles virus].

PMID- 16111275
TI  - [Diagnostic tests: Respiratory syncytial virus].

PMID- 16111276
TI  - [Diagnostic tests: Rhinovirus].

PMID- 16111277
TI  - [Diagnostic tests: Echo viruses].

PMID- 16111278
TI  - [Diagnostic tests: Coxsackie virus].

PMID- 16111279
TI  - [Laboratory diagnosis for poliovirus].

PMID- 16111280
TI  - [Laboratory diagnosis for non-polio enteroviruses].

PMID- 16111281
TI  - [Laboratory diagnosis for acute hemorrhagic conjunctivitis].

PMID- 16111282
TI  - [Laboratory diagnosis for enterovirus 71 infection].

PMID- 16111284
TI  - [Diagnostic tests: Avian influenza virus].

PMID- 16111283
TI  - [Diagnostic tests: Sabia virus].

PMID- 16111285
TI  - [Diagnostic tests: Serum anti-hepatitis A virus antibody and hepatitis A virus
      RNA].

PMID- 16111286
TI  - [Diagnostic tests: Serological markers of hepatitis B virus].

PMID- 16111287
TI  - [Diagnostic tests: HBV-DNA].

PMID- 16111288
TI  - [Diagnostic tests: Hepatitis C virus-related antibody].

PMID- 16111289
TI  - [Diagnostic tests: Hepatitis C virus genome (HCV RNA)].

PMID- 16111290
TI  - [Diagnostic tests: Hepatitis delta virus (HDV) marker].

PMID- 16111291
TI  - [Diagnostic tests: Hepatitis E viral marker].

PMID- 16111292
TI  - [Diagnostic tests: HGV related viral marker].

PMID- 16111293
TI  - [Diagnostic tests: Torque Teno virus].

PMID- 16111294
TI  - [Diagnostic tests: Human T lymphotropic virus type-I, HTLV-I provirus DNA].

PMID- 16111295
TI  - [Diagnostic tests: Human immunodeficiency virus type 1, type 2 (HIV-1, HIV 2)].

PMID- 16111296
TI  - [Progress in detection of autoantibodies and analysis of autoantigens].

PMID- 16111297
TI  - [Diagnostic tests: Rheumatoid factor].

PMID- 16111298
TI  - [RA-related autoantibodies (anti-calpastatin, anti-gp130-RAPS, and anti-FRP
      antibodies)].

PMID- 16111299
TI  - [LE cell test].

PMID- 16111300
TI  - [Immunologic tests: Antinuclear antibody].

PMID- 16111301
TI  - [Immunologic tests: Anticentromere antibody].

PMID- 16111302
TI  - [Immunologic tests: Anti-histone antibodies].

PMID- 16111303
TI  - [Immunologic tests: Anti-DNA antibodies].

PMID- 16111304
TI  - [Diagnostic tests: Anti-agalactosyl IgG antibody].

PMID- 16111305
TI  - [Immunologic tests: Anti citrullinated protein (filaggrin/CCP) antibodies].

PMID- 16111306
TI  - [Diagnostic tests: Anti-neuronal nuclear antibodies, type 1 and type 2].

PMID- 16111307
TI  - [Diagnostic tests: Anti-Purkinje cell antibody (Anti-Yo/type 1 antibody)].

PMID- 16111308
TI  - [Immunologic tests: Anti-RNP . Sm antibodies (anti-U1 RNP antibodies)].

PMID- 16111309
TI  - [Immunologic tests: Anti-Sm antibodies].

PMID- 16111310
TI  - [Immunologic tests: Anti ribosome antibody].

PMID- 16111311
TI  - [Immunologic tests: Anti-rNA polymerase antibody].

PMID- 16111312
TI  - [Immunologic tests: Anti SS-A/Ro, anti SS-B/La antibody].

PMID- 16111313
TI  - [Immunologic tests: Anti-Scl-70 antibody (anti-topoisomerase I antibody)].

PMID- 16111314
TI  - [Immunologic tests: Anti-polymyositis-scleroderma (PM-Scl) antibody].

PMID- 16111315
TI  - [Immunologic tests: Anti-Jo-l antibody (anti-histidyl transfer RNA synthetase
      antibody)].

PMID- 16111316
TI  - [Immunologic tests: Anti-PL 7 antibodies, anti-PL-12 antibodies, and other anti
      aminoacyl tRNA synthetase antibodies].

PMID- 16111317
TI  - [Immunologic tests: Anti-U1 RNP and U2 RNP antibodies].

PMID- 16111318
TI  - [Immunologic tests: Anti-U3RNP (fibrillarin) and anti-7-2RNP (Th/To) antibodies].

PMID- 16111319
TI  - [Immunologic tests: Anti Ki/PA28gamma antibody].

PMID- 16111320
TI  - [Immunologic tests: Anti-Ku antibodies].

PMID- 16111321
TI  - [Diagnostic tests: Anti-poly ADP-ribose antibody].

PMID- 16111322
TI  - [Diagnostic tests: Anti-proliferating cell nuclear antigen (PCNA) antibody].

PMID- 16111323
TI  - [Immunologic tests: Anti-tropomyosin antibody].

PMID- 16111324
TI  - [Immunologic tests: Anti-mitochondrial antibody].

PMID- 16111325
TI  - [Immunologic tests: Antipituitary antibodies].

PMID- 16111326
TI  - [Immunologic tests: Anti liver-kidney microsome antibody].

PMID- 16111327
TI  - [Immunological tests: Anti-cytochrome P 450 2D6 antibody (CYP2D6 antibody)].

PMID- 16111328
TI  - [Immunologic tests: Anti-smooth muscle antibody].

PMID- 16111329
TI  - [Immunologic tests: Hepatocyte membrane antibody].

PMID- 16111330
TI  - [Immunological tests: Parietal cell antibody].

PMID- 16111331
TI  - [Immunologic tests: Intrinsic factor antibody].

PMID- 16111332
TI  - [Immunologic tests: Anticolon antibody].

PMID- 16111333
TI  - [Immunological tests: Anti skeletal muscle antibody].

PMID- 16111334
TI  - [Immunologic tests: Antimyocardial antibody].

PMID- 16111335
TI  - [Immunological tests: Anti desmoglein 1 and 3 antibody].

PMID- 16111336
TI  - [Immunological tests: Antiadrenocortical antibody].

PMID- 16111337
TI  - [Immunologic tests: Anti-gonad antibodies].

PMID- 16111338
TI  - [Immunologic tests: Anti-sperm antibody].

PMID- 16111339
TI  - [Immunologic tests: Anti-acetylcholine receptor antibody (non-blocking type and
      blocking type antibodies)].

PMID- 16111340
TI  - [Immunologic tests: Anti-MuSK antibody].

PMID- 16111341
TI  - [Anti-MOG immunoglobulin IgM].

PMID- 16111342
TI  - [Immunologic tests: Myelin basic protein and anti-myelin basic protein antibody].

PMID- 16111343
TI  - [Immunologic tests: Anti glomerular basement membrane antibody].

PMID- 16111344
TI  - [Immunologic tests: Anti-reticulin antibody].

PMID- 16111345
TI  - [Immunological tests: Anti-brush border antibody].

PMID- 16111346
TI  - [Immunologic tests: Anti-mitotic spindle associated antibody].

PMID- 16111347
TI  - [Immunologic tests: Anti-neutrophil antibody].

PMID- 16111348
TI  - [Immunologic tests: Antilymphocyte antibody].

PMID- 16111349
TI  - [Immunological tests: Red cell autoantibodies].

PMID- 16111350
TI  - [Immunologic tests: Anti-platelet autoantibody].

PMID- 16111351
TI  - [Immunological tests: Anti-neutrophil cytoplasmic antibody].

PMID- 16111352
TI  - [Immunologic tests: Anti-calmodulin antibody].

PMID- 16111353
TI  - [Immunologic tests: Anti-carbonic anhydrase II antibody].

PMID- 16111354
TI  - [Immunological tests: Anti-vascular endothelial cell antibody].

PMID- 16111355
TI  - [Immunologic tests: Anti-Survivin and anti-Livin antibodies].

PMID- 16111356
TI  - [Immunologic tests: Anti-Sp100 antibody].

PMID- 16111357
TI  - [Immunological tests: Anti-type II collagen auto antibody].

PMID- 16111358
TI  - [Immunological tests: Anti-vimentin antibodies].

PMID- 16111359
TI  - [Immunologic tests: Anti-sulfatide antibody].

PMID- 16111360
TI  - [Antibodies to GM1 and GQ1b gangliosides].

PMID- 16111361
TI  - [On basic blood phenotype of Japanese].

PMID- 16111362
TI  - [Clinical significance of screening test for irregular antibodies].

PMID- 16111363
TI  - [ABO blood group and subtype].

PMID- 16111364
TI  - [Rh blood group system and Rh antibodies].

PMID- 16111365
TI  - [Lewis blood group system and their antibodies (anti Le(a), anti-Le(b))].

PMID- 16111366
TI  - [MNSs blood group system and antibodies (anti-M, -N, -S and -S antibodies)].

PMID- 16111367
TI  - [P blood group system and P antibodies].

PMID- 16111368
TI  - [Kell blood group system and antibodies].

PMID- 16111369
TI  - [Duffy blood groups and their antibodies (anti Fy(a) antibody, anti Fy(b)
      antibody)].

PMID- 16111370
TI  - [Diego blood system and the antibodies].

PMID- 16111371
TI  - [I blood group system and antibodies].

PMID- 16111372
TI  - [Kidd blood group system and antibodies (anti-Jk(a), anti-Jk(b))].

PMID- 16111373
TI  - [Lutheran blood group system and antibody].

PMID- 16111374
TI  - [Xg blood group system and anti-Xg(a) antibody].

PMID- 16111375
TI  - [Ok(a) antigen and anti-Ok(a)].

PMID- 16111376
TI  - [Cross matching test].

PMID- 16111377
TI  - [Galactosaminyltransferase activity test].

PMID- 16111378
TI  - [Direct and indirect anti-globulin test].

PMID- 16111379
TI  - [Anti-D human immunoglobulin test].

PMID- 16111380
TI  - [Antibody elution from red blood cells].

PMID- 16111381
TI  - [Donath-Landsteiner test].

PMID- 16111382
TI  - [Blood group incompatible pregnancy].

PMID- 16111383
TI  - [Introduction for HLA typing; variety of antigens, condition of sample
      collection, applications of testing, and clinical significance].

PMID- 16111384
TI  - [Serological typing of HLA].

PMID- 16111385
TI  - [Mixed lymphocyte culture].

PMID- 16111386
TI  - [DNA typing of HLA alleles].

PMID- 16111387
TI  - [Analysis of HLA chimerism].

PMID- 16111388
TI  - [Cell surface marker analysis (single-color and two-color analysis) with flow
      cytometry].

PMID- 16111389
TI  - [Flow cytometric cell analysis by surface antigen according to CD grouping].

PMID- 16111390
TI  - [Blast gating method for flow cytometric analysis of leukemia cells].

PMID- 16111391
TI  - [Percentage of human T-, B-cells].

PMID- 16111392
TI  - [Percentage of T cells bearing receptors for IgG or IgM Fc portion].

PMID- 16111393
TI  - [Natural killer cell activity, activity of lymphokine-activated killer cells (LAK
      activity), and killer-helper factors (KHF)].

PMID- 16111394
TI  - [Macrophage migration inhibition test (MIT), leukocyte migration inhibition test
      (LMT)].

PMID- 16111395
TI  - [Immunologic tests: Lymphocyte blastogenesis].

PMID- 16111396
TI  - You are the pioneers of patient safety.

PMID- 16111397
TI  - Conflict of interest in adverse event reporting.

PMID- 16111398
TI  - JCAHO and IS09000--how do you choose?

PMID- 16111399
TI  - Should JCAHO's goal 6 on clinical alarms be reinstated?

PMID- 16111400
TI  - What's your QMS end game?

PMID- 16111401
TI  - Prioritizing verification checks and preventive maintenance.
AB  - The role of the equipment technician has not changed in 30 years, but the
      equipment and the staff using it has. It is clearly time to update our procedures
      and methodology. Some of these time-consuming PM tasks yield no measurable
      benefit to neither our industry nor to our customers. All of the additional
      requirements placed onto us recently indicate that our customers' needs have
      changed and negates our obsession to place inspection stickers all over the
      place. We need to adapt to the changing environment and become the technicians of
      the 21st century by abandoning long, outdated practices such as mindless monthly
      inspections. We are valuable to our customers and our employers for what we know-
      not what we do. Not just anyone can walk into anactive operating room theater and
      find a bad patient cableon the spot. We alone can control the work that we do. We
      are the pinnacle of all electronics repair with the duties and responsibilities
      that go along with it. Isn't it abouttime we acted like it?

PMID- 16111402
TI  - Troubleshooting therapeutic ultrasound: measuring output power and caring for
      transducers.

PMID- 16111403
TI  - Are you ready for unannounced surveys?

PMID- 16111404
TI  - What the code of federal regulations means to you.

PMID- 16111405
TI  - Clinical laboratory equipment.

PMID- 16111406
TI  - DICOM: key concepts--part II.
AB  - The objective of these two installments of IT World was to give a general
      overview of DICOM and to take a look at different parts of the standard to get a
      sense of its main themes. We found that the standard provides a common reference
      for all developers but does not impose a single type of implementation. This
      allows for innovation. The standard is also built for flexibility, able to adapt
      to new modalities that have a need to communicate. The speedy acceptance of DICOM
      by the medical imaging industry is opening new possibilities for healthcare
      organizations to increase the quality while decreasing the cost of patient care.
      All of the DICOM networked supporting medical equipment as well as the
      organization's computer systems made by multiple original equipment manufacturers
      and located at one site or many sites can communicate by means of DICOM. This
      gives us the opportunity for medical images to be captured and communicated
      quicker. The result enables physicians to make diagnoses and treatment decisions
      sooner. It's all good stuff and even more reason why we should endeavor to
      understand the basics of DICOM. DICOM is here to stay!

PMID- 16111407
TI  - Centralized MUSE system extends capability to small facilities.

PMID- 16111408
TI  - Finding the key to job satisfaction: it's in your hands.

PMID- 16111409
TI  - Understanding the human body: sharpening your medical terminology skills--part 2.

PMID- 16111410
TI  - The critical path to new medical devices.

PMID- 16111411
TI  - Human factors and the control of medical error.

PMID- 16111412
TI  - A new intelligent bed care system for hospital and home patients.
AB  - An intelligent bed-care system has been developed for monitoring patient
      movements and behavior in the hospital and at home in order to prevent injuries
      from falls, a major problem in health care facilities. Falls, as well as patient
      activity immediately preceding falls (i.e. exiting the bed), are especially
      dangerous when infusion extubation also occurs. This new system detects in-bed
      infusion fluid leaks, bleeding due to infusion-tube pullout, and urine resulting
      from incontinence. It employs stainless steel tape and wire noncontacting
      electrodes, several linear integrated circuits, and a low-power, 8-bit single
      chip microcomputer The electrodes are installed between the bed mattress and
      sheet to record changes in an always-present alternating current (AC) voltage,
      which is induced on the patient's body by electrostatic coupling from a 100-V, 60
      Hz alternating current power line around the bed. The microcomputer uses changes
      in the induced alternating current voltage to detect the patient's movements
      before and after leaving the bed, as well as any fluid leakage. The microcomputer
      alerts the nursing station, via the nurse call system or personal handy phone
      (PHS), that the patient is in an active state; has a dangerous posture on the
      bed; is contaminating the sheet due to leaking, bleeding or incontinence; or is
      out of bed.

PMID- 16111413
TI  - A fuzzy inference system to evaluate contract service provider performance.
AB  - This paper puts forward a fuzzy inference system for evaluating the quality
      performance of service contract providers. An Application Service Provider was
      designed and put online, featuring surveys to establish the most useful
      indicators to evaluate the quality of the service. This model was implemented in
      10 separate hospitals. As a result, the service cost-acquisition cost ratio in
      these cases was reduced from 16.14% to 6.09% in the period 2001-January 2003.

PMID- 16111414
TI  - Top 10 things OR nurses should know about AAMI standards.

PMID- 16111415
TI  - Elevating the biomed profession down under and beyond.

PMID- 16111416
TI  - Activated eosinophils in nasal polyps: a comparison of asthmatic and non
      asthmatic patients.
AB  - OBJECTIVES: There is a recognized clinical association between nasal polyps and
      asthma. Nasal polyps and the airways of asthmatic patients demonstrate marked
      eosinophilia suggesting that this inflammatory cell may have a key role to play
      in both conditions. The objective of this study was to determine whether nasal
      polyps from patients with asthma had a greater density of activated eosinophils
      than patients with no associated respiratory disease. DESIGN: Archived specimens
      were retrieved from patients who had undergone nasal polyp surgery and their case
      notes reviewed. Activated eosinophils were identified using immunohistochemistry
      for a monoclonal antibody to secreted eosinophil cationic protein (EG2). SETTING:
      Teaching hospital otolaryngology unit. PARTICIPANTS: Consecutive patients who had
      undergone nasal polyp surgery in 1994 were recruited. The diagnosis of asthma was
      based on a documented physician diagnosis and appropriate drug treatment. Twenty
      four asthmatic and 35 non-asthmatic patients were studied. MAIN OUTCOME MEASURES:
      Eosinophil density was measured using a standardized counting technique. RESULTS:
      Asthmatic patients were significantly more likely to have had previous polyp
      surgery (chi-square test: P < 0.05). Areas of intense eosinophilia were
      identified in all samples. There was a significant greater degree of activated
      eosinophilia in the asthmatic patients (t-test: P < 0.05). CONCLUSIONS: We have
      demonstrated a higher number of previous operations in asthmatic patients, and
      also a greater degree of activated eosinophilia in asthmatic polyps compared with
      non-asthmatics. This would suggest that eosinophil activity has a role to play in
      the pathogenesis of nasal polyps.

PMID- 16111417
TI  - Double-blind randomized controlled study of coblation tonsillotomy versus
      coblation tonsillectomy on postoperative pain in children.
AB  - OBJECTIVES: The purpose of this study was to establish if children experienced
      any difference in pain, between coblation tonsillectomy and coblation
      tonsillotomy. DESIGN: A double-blind randomized controlled trial was performed.
      SETTING: District general hospital department of Otolaryngology. PARTICIPANTS:
      Eighteen children listed for tonsillectomy were recruited into the study. Each
      was randomly assigned either tonsillotomy or tonsillectomy in the right tonsil.
      The contralateral tonsil was removed by the other method. In the first 24-h
      period (while in hospital) the children were interviewed at 2, 5, 10 and 24 h to
      quantify the pain they perceived in right and left sides. There was a four point
      visual analogue scoring system for monitoring pain. The power of the study was
      80%. In this study the patients were their own controls. MAIN OUTCOME MEASURES:
      Visual analogue pain scores were plotted against time and the area under the
      curves was calculated (AUC). RESULTS: The AUC mean difference was 0.47. A t-test
      for the difference gives a P-value of 0.85 and a 95% confidence interval for
      difference is -0.79 to 5.73, which clearly contains zero. Using AUC as a combined
      pain score there is no statistically significant difference between tonsillotomy
      and tonsillectomy (power value of 80%). CONCLUSIONS: There is no demonstrable
      statistical difference between techniques when measuring pain experienced by
      children in the 24-h postoperative period.

PMID- 16111418
TI  - The use of camera mobile phone to assess emergency ENT radiological
      investigations.
AB  - OBJECTIVES: To determine the accuracy of assessment of common ENT emergency
      radiological investigations using mobile phone digital images. DESIGN:
      Prospective case controlled series. SETTING: Tertiary referral otolaryngology
      centre. PARTICIPANTS: Fourteen randomly selected patients who underwent emergency
      ENT radiological investigations over a 1-month period. MAIN OUTCOME MEASURES: The
      accuracy and confidence of six ENT consultants and five specialist registrars in
      making diagnoses based on a brief history and assessment of CT scans and X-ray
      images taken from and transmitted via a mobile phone, compared with examination
      of the same films on a conventional X-ray box. RESULTS: With 14 films, a total of
      154 cases were assessed by the 11 subjects. All doctors made the correct
      diagnosis for every case examined. Overall, the relative confidence of diagnosis
      was ranked highly for both image media, although the overall confidence of
      diagnosis using the X-ray box was significantly greater than the mobile phone
      (95% CI upper bound = 1.6 lower bound = 0.9; paired t-test P < 0.0001). The
      seniority of the clinician did not predict a difference in the confidence of
      diagnosis (P = 0.3). There is no statistical relationship between confidence of
      diagnosis of the original films and degradation of film quality on the mobile
      phone (P = 0.7). CONCLUSIONS: The accuracy and confidence of diagnosis of common
      ENT emergency radiological investigations using mobile phone digital images seem
      compatible with X-ray box. Financially it is a much cheaper than conventional
      telemedicine technology. It may be used to augment information sent to non
      resident specialists in the management of emergency ENT cases.

PMID- 16111419
TI  - Clinical predictors in obstructive sleep apnoea patients with calibrated
      cephalometric analysis--a new approach.
AB  - AIM: Utilization of a new method to accurately quantify differences in
      cephalometric parameters between obstructive sleep apnoea (OSA) and normal
      patients, and to identify good predictors for OSA. To illustrate the ethnic
      differences in cephalometry. METHOD: This prospective study involves 106 South
      east Asians. A calibrated catheter is inserted into the upper airway during
      standard cephalometry to obtain the precise magnification and allow exact
      measurement of anatomical parameters of cephalometry in both erect and supine
      positions. RESULTS: The OSA patients have longer lower-facial length, narrower
      skull base, shorter and receding mandible, smaller posterior airway space (PAS),
      narrower retropalatal space, longer and thicker soft palate, smaller hard and
      soft palate angles longer tongue length and more inferiorly displaced hyoid. For
      the palatal level, retropalatal distance of 11.2 mm cut-off/predictive value for
      male (receiver operating characteristics (ROC) = 0.8414 with PPV = 77.46, NPV =
      90.00) and 5.5 mm for female (ROC = 0.9180 with PPV = 100.00, NPV = 84.21) at
      erect position were selected. For retrolingual level, erect PAS of 10.1 mm cut
      off/predictive value for male (ROC = 0.7000 with PPV = 78.38, NPV = 37.78), 5.3
      mm for female (ROC = 0.7227 with PPV = 75.00, NPV = 75.00) were selected. Our
      study showed that South-east Asians have different cephalometric values compared
      with White people, Black people and Hispanics. CONCLUSION: This new method of
      cephalometry using a calibrated catheter provides an accurate and simple method
      of obtaining precise cephalometric measurements. There is no cephalometric data
      on OSA from South-east Asia available. These results suggested that surgeons
      managing OSA patients and using cephalometry as a diagnostic method should have a
      set of normative and OSA cephalometric values that apply to their local
      populations.

PMID- 16111420
TI  - Three-year follow-up of children with postmeningitic deafness and partial
      cochlear implant insertion.
AB  - OBJECTIVES: To evaluate the long-term outcome of children with postmeningitic
      deafness and partial insertion of the Nucleus electrode array, and to compare
      their speech perception performance with that of children with full insertion of
      the electrode array. DESIGN: A battery of seven speech perception tests was
      administered to 25 children with a cochlear implant (CI). Results were reduced
      into one score: equivalent hearing loss (EHL). SETTING: Tertiary referral centre.
      PARTICIPANTS: The partial insertion group comprised seven children, mean age at
      implantation 5.5 years, mean duration of deafness 3.6 years. The full-insertion
      control group comprised 18 children. Mean age at implantation: 4.4 years; mean
      duration of deafness: 2.9 years. All the children became deaf between 0 and 3
      years of age. MAIN OUTCOME MEASURES: Over a 3-year follow-up period, the children
      with partial insertion showed continuing progress, although there was wide
      variation in performance and the rate of progression. Some open-set comprehension
      could even be achieved with the insertion of only eight electrodes of a nucleus
      device. RESULTS: Three years after implantation, speech perception in the partial
      insertion children was poorer than that in the control groups with long (P <
      0.01; 95% confidence interval 7-43 dB EHL) and short duration of deafness (P <
      0.0001; 95% confidence interval 28-53 dB EHL). They showed slower progress and
      reached a poorer EHL plateau. Four of the seven children acquired open-set word
      recognition. CONCLUSIONS: Patients with partial insertion of the electrode array
      benefit from a CI, although less than patients with complete insertion.

PMID- 16111421
TI  - Extended high-frequency audiometry in patients with acoustic trauma.
AB  - OBJECTIVES: The aim of this study was to examine extended high-frequency (EHF)
      hearing in patients with acoustic trauma. DESIGN: A prospective, case-control
      study in a group of soldiers with acoustic trauma caused by shooting practice
      during basic training. SETTING: Tertiary referral centre. PARTICIPANTS: A total
      of 39 young soldiers hospitalized for hearing loss and tinnitus following
      exposure to weapon impulse noise were studied. Conventional audiometry in the
      frequency range 0.25-8 kHz and EHF audiometry in the frequency range 9-20 kHz
      were performed, both on admittance and before discharge. Thirty healthy recruits
      of similar age and sex were used as controls. MAIN OUTCOME MEASURES: Pure-tone
      threshold changes documented by conventional and EHF audiometry. RESULTS: The
      most significant differences in pure-tone thresholds on initial testing were
      found in the frequency range 0.25-11.2 kHz, and especially in the 4-8 kHz region.
      Reduction in thresholds across most frequencies was observed after treatment,
      although recovery was partial in most cases. CONCLUSIONS: The EHF audiometry adds
      no significant additional information to conventional pure-tone audiometry in
      assessing and monitoring noise-induced hearing loss.

PMID- 16111422
TI  - Interobserver reliability in evaluating postural stability between clinicians and
      posturography.
AB  - OBJECTIVES: To assess the interobserver reliability in assessing postural
      stability and to compare with results obtained by computerized posturography.
      DESIGN: Cross-sectional study. SETTING: Balance clinic, teaching hospital.
      PARTICIPANTS: 81 patients attending with a primary complaint of imbalance. MAIN
      OUTCOME MEASURES: Inter-rater reliability between two clinicians and the modified
      Clinical Test for the Sensory Interaction on Balance (mCTSIB) as assessed by the
      Neurocom VSR Balance Master platform. RESULTS: Inter-rater reliability scores
      were high (0.53-0.81) for all conditions of the mCTSIB except for the easiest,
      i.e. firm surface eyes open, where concordance levels were poor to fair.
      CONCLUSIONS: Overall there was good agreement between observers and the
      computerized mCTSIB.

PMID- 16111423
TI  - The impact of recurrent acute otitis media on the quality of life of children and
      their caregivers.
AB  - OBJECTIVE: To assess the quality of life of 384 Dutch children aged 1-7 years
      with recurrent acute otitis media (AOM), and compare it with that of children
      from four reference populations: (i) children from a general population; (ii)
      children with mild-to-moderate asthma, (iii) children with mild-to-moderately
      severe chronic illness, and (iv) US children with persistent or recurrent otitis
      media. DESIGN: Survey. SETTING: A general and an academic hospital (study
      population of children with recurrent AOM, n = 384); general population (n = 225
      and 117); primary care (children with asthma, n = 64); community care (children
      with chronic illness, n = 82); and a general hospital (children with persistent
      or recurrent otitis media, n = 169). PARTICIPANTS: A total of 384 children aged 1
      7 years who had experienced at least two episodes of AOM in the preceding year
      and their caregivers. MAIN OUTCOME MEASURES: Generic and disease-specific quality
      of life as judged by the children's caregivers. Age-adjusted total and subscale
      scores were compared with those of the reference populations. RESULTS: For all
      generic questionnaires, children with recurrent AOM had poorer scores than
      children from the general population. Quality of life of children with four or
      more episodes of AOM in the preceding year was poorer than that of children with
      two to three episodes. Children with recurrent AOM scored lower on the health
      related questionnaire than children with mild-to-moderately severe chronic
      illness. Quality of life of the present study population was similar to those of
      children with asthma and US children with chronic otitis media with effusion or
      recurrent AOM. CONCLUSION: Recurrent AOM has a considerable negative impact on
      the quality of life of children and causes concern to their caregivers. These
      effects are proportional to the severity of the condition. Professionals involved
      in the care of children with OM should be aware that OM not only affects physical
      functioning but also general well-being of the child and its family. These
      outcomes should therefore be included in the evaluation of the child with otitis
      media both in the clinical and research setting.

PMID- 16111424
TI  - The Ossicle Bank of the University Medical Centre (UMCU), The Netherlands.

PMID- 16111425
TI  - Speech-in-noise as an indicator of benefit from grommets--is an age-dependent cut
      off necessary?

PMID- 16111426
TI  - How we do it: the Farrior-Olaizola mastoidectomy technique in the management of
      squamous chronic otitis media.

PMID- 16111427
TI  - How we do it: Jain tonsil 'A' frame--a solution to slipping rods.

PMID- 16111428
TI  - How we do it: postoperative tissue oxygen monitoring in microvascular free flaps.

PMID- 16111429
TI  - How we do it: head and neck cancer waiting times.

PMID- 16111430
TI  - Relation between change of hearing and (modified) Amsterdam Inventory for
      Auditory Disability and Handicap Score.

PMID- 16111431
TI  - The ultrasonically activated scalpel versus bipolar diathermy for tonsillectomy:
      a prospective randomized trial.

PMID- 16111432
TI  - A randomized trial of local anaesthetic in treatment of quinsy.

PMID- 16111433
TI  - Effects of omega-3 fatty acids on eye health.

PMID- 16111434
TI  - Acute stroke: evaluation and treatment.

PMID- 16111435
TI  - Effects of omega-3 fatty acids on mental health.

PMID- 16111436
TI  - The incidence of dementia in England and Wales: findings from the five identical
      sites of the MRC CFA Study.
AB  - BACKGROUND: Although incidence of dementia is known to vary between nations,
      variation within country has not been explored because most incidence studies are
      single site or have insufficient numbers to compare sites. Few countries have
      conducted multisite incidence studies in order to facilitate national
      comparisons. This study aims to provide robust measures of the variation of the
      incidence of dementia across sites within England and Wales and produce overall
      estimates by age and sex. METHODS AND FINDINGS: The Medical Research Council
      Cognitive Function and Ageing Study used identical methodology in five diverse
      sites across the United Kingdom, each with different risk patterns and mortality
      rates. Incidence has been estimated using likelihood-based methods between the
      first two waves of interviews. Incidence rates rise with age, particularly above
      the age of 75 y, from 6.7 [corrected] (95% confidence interval, 3.8 [corrected]
      12.4 [corrected]) per 1,000 person years at age 65-69 y to 68.5 [corrected] (95%
      confidence interval, 52.5 [corrected]-88.1 [corrected]) per 1,000 person years at
      age 85 y and above. The rate of increase for both sexes is marked, and continues
      into the oldest age groups. Hence, it is estimated that approximately 163,000
      [corrected] new cases of dementia occur in England and Wales each year. There is
      no convincing evidence of variation across sites, and incidence rates do not
      reflect the variations in the prevalence of possible risk factors in these sites.
      CONCLUSION: There is no evidence, within England and Wales, of variation in
      dementia incidence across sites. Dementia incidence rates do not tail off at the
      oldest ages.

PMID- 16111437
TI  - The genomics of disulfide bonding and protein stabilization in thermophiles.
AB  - Thermophilic organisms flourish in varied high-temperature environmental niches
      that are deadly to other organisms. Recently, genomic evidence has implicated a
      critical role for disulfide bonds in the structural stabilization of
      intracellular proteins from certain of these organisms, contrary to the
      conventional view that structural disulfide bonds are exclusively extracellular.
      Here both computational and structural data are presented to explore the
      occurrence of disulfide bonds as a protein-stabilization method across many
      thermophilic prokaryotes. Based on computational studies, disulfide-bond richness
      is found to be widespread, with thermophiles containing the highest levels.
      Interestingly, only a distinct subset of thermophiles exhibit this property. A
      computational search for proteins matching this target phylogenetic profile
      singles out a specific protein, known as protein disulfide oxidoreductase, as a
      potential key player in thermophilic intracellular disulfide-bond formation.
      Finally, biochemical support in the form of a new crystal structure of a
      thermophilic protein with three disulfide bonds is presented together with a
      survey of known structures from the literature. Together, the results provide
      insight into biochemical specialization and the diversity of methods employed by
      organisms to stabilize their proteins in exotic environments. The findings also
      motivate continued efforts to sequence genomes from divergent organisms.

PMID- 16111438
TI  - The road ahead in diabetes management.

PMID- 16111439
TI  - Reducing patient drug acquisition costs can lower diabetes health claims.
AB  - Concerned about rising prevalence and costs of diabetes among its employees,
      Pitney Bowes Inc recently revamped its drug benefit design to synergize with
      ongoing efforts in its disease management and patient education programs.
      Specifically, based on a predictive model showing that low medication adherence
      was linked to subsequent increases in healthcare costs in patients with diabetes,
      the company shifted all diabetes drugs and devices from tier 2 or 3 formulary
      status to tier 1. The rationale was that reducing patient out-of-pocket costs
      would eliminate financial barriers to preventive care, and thereby increase
      adherence, reduce costly complications, and slow the overall rate of rising
      healthcare costs. This single change in pharmaceutical benefit design immediately
      made critical brand-name drugs available to most Pitney Bowes employees and their
      covered dependents for 10% coinsurance, the same coinsurance level as for generic
      drugs, versus the previous cost share of 25% to 50%. After 2 to 3 years,
      preliminary results in plan participants with diabetes indicate that medication
      possession rates have increased significantly, use of fixed-combination drugs has
      increased (possibly related to easier adherence), average total pharmacy costs
      have decreased by 7%, and emergency department visits have decreased by 26%.
      Hospital admission rates, although increasing slightly, remain below the
      demographically adjusted Medstat benchmark. Overall direct healthcare costs per
      plan participant with diabetes decreased by 6%. In addition, the rate of increase
      in overall per-plan-participant health costs at Pitney Bowes has slowed markedly,
      with net per-plan-participant costs in 2003 at about 4000 dollars per year versus
      6500 dollars for the industry benchmark. This recent moderation in overall
      corporate health costs may be related to these strategic changes in drug benefit
      design for diabetes, asthma, and hypertension and also to ongoing enhancements in
      the company's disease management and wellness programs.

PMID- 16111440
TI  - Factors driving diabetes care improvement in a large medical group: ten years of
      progress.
AB  - The purpose of this study was to document trends in diabetes quality of care and
      coinciding strategies for quality improvement over 10 years in a large medical
      group. Adults with diagnosed diabetes mellitus were identified each year from
      1994 (N = 5610) to 2003 (N = 7650), and internal medical group data quantified
      improvement trends. Multivariate analysis was used to identify factors that did
      and did not contribute to improvement trends. Median glycosylated hemoglobin A1C
      (A1C) levels improved from 8.3% in 1994 to 6.9% in 2003 (P <.001). Mean low
      density lipoprotein (LDL) cholesterol measurements improved from 132 mg/dL in
      1995 to 97 mg/dL in 2003 (P <.001). Both A1C (P <.01) and LDL improvement (P
      <.0001) were driven by drug intensification, leadership commitment to diabetes
      improvement, greater continuity of primary care, participation in local and
      national diabetes care improvement initiatives, and allocation of
      multidisciplinary resources at the clinic level to improve diabetes care.
      Resources were spent on nurse and dietitian educators, active outreach to high
      risk patients facilitated by registries, physician opinion leader activities
      including clinic-based training programs, and financial incentives to primary
      care clinics. Use of endocrinology referrals was stable throughout the period at
      about 10% of patients per year, and there were no disease management contracts to
      outside vendors over the study period. Electronic medical records did not
      favorably affect glycemic control or lipid control in this setting. This primary
      care-based system achieved A1C and LDL reductions sufficient to reduce
      macrovascular and microvascular risk by about 50% according to landmark studies;
      further risk reduction should be attainable through better blood pressure
      control. Strategies for diabetes improvement need to be customized to address
      documented gaps in quality of care, provider prescribing behaviors, and patient
      characteristics.

PMID- 16111441
TI  - Best practices in diabetes management: getting more patients to goal.

PMID- 16111442
TI  - Evolving shifts in otitis media pathogens: relevance to a managed care
      organization.
AB  - The microbiological landscape of acute otitis media (AOM) has been relatively
      constant over the past half century. Because of this stability, empiric
      management of AOM was a common and efficient practice. Recently, there has been a
      proportional shift in the microbiology of AOM, bringing the choices for empiric
      therapy into question. Because of this shift, managed care organizations should
      review their formularies to ensure that they are structured to include and
      promote the use of appropriate antibiotics. This article explores the background
      and events leading up to the shift in AOM microbiology; discusses the clinical
      consequences and the future implications of the shift, such as increased costs
      associated with treatment failures, its impact on new vaccines and new-onset AOM
      and related disease states, such as sinusitis; and describes why these factors
      should be considered by managed care decision makers in their formulary
      deliberations.

PMID- 16111443
TI  - Improving acute otitis media outcomes through proper antibiotic use and
      adherence.
AB  - This article will discuss how therapy adherence may have an impact on acute
      otitis media (AOM) outcomes. Although the relationship between therapy adherence
      and treatment failures in AOM has not been proved beyond question, many believe
      that adherence with antibiotic therapy plays a key role in patient outcomes. Poor
      adherence may contribute to treatment failures; treatment failures are known to
      result in poorer health outcomes, higher total costs of care, and an increased
      potential for bacterial resistance. As such, managed care organizations should
      consider strategies for achieving better patient adherence with antibiotic
      regimens for AOM.

PMID- 16111444
TI  - Recombinant activated Factor VII in major surgery and trauma patients: a
      response.
AB  - The review article by Wilson et al. (Expert Opin. Drug Saf., 2005) on recombinant
      activated Factor VII (rFVIIa) offers some valuable insights into the ongoing
      exploration of this agent in the management of uncontrolled bleeding--an area of
      high unmet clinical need. This editorial highlights that the chosen citation of
      Riou et al. (Shock, 2004), in reference to two parallel studies conducted in
      trauma patients with blunt and penetrating injury, was both a report of an early
      analysis of the data, and was only one of several abstracts on these studies
      published in 2004. The authors of this editorial believe that the inclusion of
      the other published abstracts in this series would have provided a more
      comprehensive and balanced overview of recombinant activated Factor VII.

PMID- 16111445
TI  - The current status of heroin prescription treatment for heroin dependence.
AB  - Heroin prescription (HP) to treat severe heroin dependence has been available to
      few patients in the UK for several decades with limited, but generally
      favourable, evaluation. In the last decade, large trials have been reported from
      two countries, are presently underway in three other countries and under
      consideration in several other countries. The standard pharmacological treatments
      for heroin dependence, methadone and buprenorphine, attract and retain many more
      drug users than other pharmacological or nonpharmacological treatments and are
      strongly supported by evidence of efficacy, effectiveness, safety and cost
      effectiveness. On present evidence, HP is feasible and safe with limited, but
      increasing, evidence of efficacy and effectiveness. Although HP is more expensive
      than methadone, there is some evidence of cost effectiveness. HP is, at present,
      only considered a therapeutic option for a small minority of treatment
      refractory, severely heroin-dependent persons in developed countries with
      comprehensive treatment systems.

PMID- 16111446
TI  - Drug-drug interactions and tolerance in combining antituberculosis and
      antiretroviral therapy.
AB  - Worldwide, tuberculosis (TB) is one of the most important infectious diseases in
      subjects with HIV infection. Although effective therapy is available for both
      conditions, there are major problems in the concurrent treatment of HIV and TB co
      infection. In this article the knowledge available on drug-drug interactions
      between anti-HIV and anti-TB compounds is analysed, particularly with regard to
      pharmacological interactions secondary to interference with cytochrome P450
      enzymes. Within the same setting, facts and possible interpretations of the
      problems encountered in terms of tolerance and safety of the concurrent treatment
      of TB and HIV are also reviewed. Current guidelines, as well as additional
      possible strategies to be adopted in this particular co-morbidity setting are
      discussed.

PMID- 16111447
TI  - Risk of skin reactions when using ibuprofen-based medicines.
AB  - Adverse reactions to drugs are a frequent cause of morbidity and medical
      consultation; it is no surprise that nonsteroidal anti-inflammatory drugs
      (NSAIDs) run second, after antibiotics, mainly of the beta-lactam group
      (penicillins and cephalosporins). Numerous clinical pictures involving the skin-
      various morbilliform rashes, urticaria and angioedema as the most common--due to
      hypersensitivity to a particular NSAID (i.e., ibuprofen) have been described;
      other clinically defined skin diseases such as vasculitis, Steven-Johnson's
      syndrome, photosensitivity, fixed drug eruptions, livedo-like dermatitis, linear
      drug eruption, lichenoid drug eruption, exanthematous pustulosis, eczematous
      eruption, contact dermatitis and pemphigoid have received the attention of
      physicians. Extensive use around the world makes it interesting to investigate
      adverse cutaneous reactions to ibuprofen and other members of the propionic acid
      derivative group, to ascertain their prevalence, clinical presentation and
      prevention. This paper presents a review of published literature concerning
      cutaneous hypersensitivity reactions to ibuprofen and related arylpropionic
      acids.

PMID- 16111448
TI  - The safety and tolerability of atypical antipsychotics in bipolar disorder.
AB  - Atypical antipsychotics (aAPs), have become a first-line treatment option, both
      in schizophrenia and bipolar disorders. Almost all aAPs now have proven efficacy
      in acute mania, some also in bipolar depression and in maintenance treatment.
      This provides reliable data on their safety and tolerability in this particular
      group of patients. This review focuses on the safety and tolerability of aAPs in
      the treatment of bipolar disorders. Both tolerability, for example,
      extrapyramidal symptoms, and safety issues, for example, occurrence of weight
      gain and hyperglycaemia, will be highlighted for olanzapine, quetiapine,
      risperidone, ziprasidone and aripiprazole.

PMID- 16111449
TI  - Safety of antiepileptic drugs during pregnancy.
AB  - Women with epilepsy taking antiepileptic drugs during pregnancy have been shown
      to have an increased risk of having a child with a major malformation. There is
      some recent evidence to suggest that these drugs may also affect cognitive and
      behavioural development. Epilepsy is a common neurological condition and women
      with epilepsy constitute a significant number of pregnancies in the UK each year.
      Some of the drugs used to treat epilepsy are increasingly being used in the
      treatment of migraine and other pain syndromes and also in psychiatry principally
      for the control of bipolar affective disorder. This article looks at the evidence
      currently available in assessing the safety of the individual agents used in
      pregnancy.

PMID- 16111451
TI  - Is it safe to use antidepressants after a stroke?
AB  - Depression is an important complication of stroke. Although antidepressants are
      widely used for the treatment of poststroke depression (PSD), prescription is
      critically influenced by their safety, tolerability and by the impact on co
      morbidities. The authors reviewed the literature on the use of antidepressants
      after stroke. Selective serotonin re-uptake inhibitors are effective and have a
      good profile of safety and tolerability in PSD. They are, therefore, used as
      first-line drugs in the treatment of PSD, although potential cardiovascular and
      cerebrovascular effects, drug-drug interactions and intolerability in a minority
      of patients have to be considered. Other antidepressants appear to be safe and
      effective in selected patients. PSD patients should be classified according to
      their clinical profile for the selection of the drug of choice in particular sub
      groups of patients.

PMID- 16111450
TI  - Psychiatric symptoms associated with ephedra use.
AB  - The objective of this review is to describe psychiatric adverse events occurring
      after ingestion of dietary supplements containing herbal ephedra and to assess
      the possible relationship between supplement use and the events. The authors
      reviewed all adverse event reports related to dietary supplements containing
      herbal ephedra from US FDA MedWatch files as of 30 September, 2001. Psychosis,
      mania or severe agitation, severe depression, hallucinations, delusions, suicide
      attempts, paranoia and violent behaviour were classified as serious psychiatric
      events. Events were categorised based on the amount of information supporting a
      causal relationship. Out of almost 1800 total adverse events, 57 were classified
      as both psychiatric in nature and serious. Two-thirds of these psychiatric cases
      involved patients with pre-existing psychological/psychiatric conditions and/or
      use of other mood-altering medications or illicit substances. The majority of
      case reports were insufficiently documented to make an informed judgment about a
      relationship between the use of ephedra and the adverse event in question. The
      case reports evaluated do not prove a definitive causal link between ephedra and
      psychiatric complications. However, they do raise concern that such a
      relationship may exist.

PMID- 16111452
TI  - Benefits and risks of pharmacological and surgical treatments for essential
      tremor: disease mechanisms and current management.
AB  - Essential tremor (ET) is a neurological disease (and possibly a family of
      diseases) whose most recognisable feature is an action tremor of the hands and
      occasionally of the voice and head. Current data support the view that CNS gamma
      amino-butyric acid (GABA)-ergic mechanisms may underlie ET and that the tremor
      may be further modulated by peripheral (muscle) adrenoreceptors. Potential
      pharmacotherapeutic options, targeted to influence the activity of the
      neurotransmitter GABA within the CNS and the peripheral adrenergic receptors, are
      part of the current armamentarium to treat ET. As such, primidone and propranolol
      remain the mainstays of the therapy for ET. Intramuscular injections of botulinum
      toxin A may play a role in the treatment of voice and head tremor. Surgical
      options, which are reserved for patients with severe, medically-refractory
      tremor, provide adequate tremor control in the majority of patients. As with
      other progressive neurological disorders of late life, the ability to use
      neuroprotective medications to intervene in the developing disease to either slow
      or halt the progression of the pathological process, would involve an
      understanding of underlying disease mechanisms. The understanding of these
      mechanisms in ET is limited and further study of these mechanisms is critical for
      the development of such therapies.

PMID- 16111453
TI  - Oral versus intravenous vinorelbine: clinical safety profile.
AB  - The availability of chemotherapeutic drugs administrable by oral route represents
      a step forward in the management of cancer patients. Among oral agents,
      vinorelbine is particularly interesting for its pharmacological characteristics
      and clinical efficacy. Oral vinorelbine is rapidly absorbed (1.5-3 hours) with an
      elimination half-life of approximately 40 hours. It shows a low level of binding
      to plasma proteins (13%), is highly bound to platelets (78%) and has a hepatic
      metabolism and an absolute bioavailability of 40% with a moderate and similar
      interpatient variability for the two forms. Food has no influence on the
      pharmacokinetic profile of oral vinorelbine even if nausea/vomiting is less
      frequent and less severe in the fed patients than in the fasting patients.
      Therefore, to ensure patient comfort, it is recommended that oral vinorelbine is
      administered with a snack. All the metabolites of oral vinorelbine have been
      identified and, among these, only deacetyl-vinorelbine presented activity
      demonstrating that for both oral and intravenous (i.v.) routes of administration
      the drug has the same metabolism pattern. Oral vinorelbine is eliminated mainly
      in a unconjugated form via the bile. In this process, the CYP 3A4 isoform of
      cytochrome P450 is mostly involved. Absorption of oral vinorelbine is not delayed
      in elderly patients. After oral administration, blood concentrations of
      vinorelbine in elderly patients are within the range of values observed in
      younger patients. The absolute bioavailability is close to 38% in elderly whereas
      it is close to 40% in younger patients. This difference is not significant. As
      compared to the intravenous drug, oral vinorelbine demonstrated linear
      pharmacokinetics as well an absolute bioavailability of approximately 40%, and a
      reliable dose-correspondence of 80 mg/m2 oral form --> 30 mg/m2 i.v. and 60 mg/m2
      oral --> 25 mg/m2 i.v. Therefore, i.v. and oral forms show similar
      interindividual variability, same metabolism pattern, reproducible intra-patient
      blood exposure, and same pharmacokinetic-pharmacodynamic relationship. Oral
      vinorelbine has shown significant activity in advanced non-small cell lung
      cancer. Given at 60 mg/m2/week for the first 3 administrations and then increased
      to 80 mg/m2/week achieved the same efficacy as i.v. vinorelbine in terms of
      progression-free survival, overall survival, objective response. Mild-to-moderate
      gastrointestinal toxicity, easily manageable with standard treatment was
      recorded. Reproducible efficacy compared to previously reported results with
      vinorelbine i.v. Also, in advanced breast cancer, oral vinorelbine has shown
      significant activity with a good therapeutic index. Albeit no formal comparison
      between the oral and the intravenous formulations of vinorelbine has been made,
      however, the oral route seems to offer major advantages to patients who are faced
      with a clear decrease in the frequency of hospital admissions as compared to that
      needed to give intravenous chemotherapy.

PMID- 16111457
TI  - The ODAC Chronicles: Part 6a. ODAC's structure and function.

PMID- 16111454
TI  - The role of data mining in pharmacovigilance.
AB  - A principle concern of pharmacovigilance is the timely detection of adverse drug
      reactions that are novel by virtue of their clinical nature, severity and/or
      frequency. The cornerstone of this process is the scientific acumen of the
      pharmacovigilance domain expert. There is understandably an interest in
      developing database screening tools to assist human reviewers in identifying
      associations worthy of further investigation (i.e., signals) embedded within a
      database consisting largely of background 'noise' containing reports of no
      substantial public health significance. Data mining algorithms are, therefore,
      being developed, tested and/or used by health authorities, pharmaceutical
      companies and academic researchers. After a focused review of postapproval drug
      safety signal detection, the authors explain how the currently used algorithms
      work and address key questions related to their validation, comparative
      performance, deployment in naturalistic pharmacovigilance settings, limitations
      and potential for misuse. Suggestions for further research and development are
      offered.

PMID- 16111459
TI  - Highlights of the American Society of Clinical Oncology annual meeting 2005. 13
      17 May, 2005, Florida, USA.

PMID- 16111461
TI  - Use of goserelin in the treatment of breast cancer.
AB  - Gonadotropin-releasing hormone analogs are, alongside tamoxifen, one of the most
      commonly used drugs in the treatment of pre-/perimenopausal endocrine-responsive
      breast cancer. Goserelin, as a principal agent of this class of drugs, is mainly
      investigated in clinical trials. The indirect comparison of goserelin with
      tamoxifen as a single drug in the adjuvant setting showed similar efficacy.
      Furthermore, goserelin is as effective as cyclophosphamide, methotrexate and 5
      fluorouracil chemotherapy, and total endocrine blockade as a combination of
      gonadotropin-releasing hormone analog and tamoxifen showed a comparable benefit
      with anthracycline-containing adjuvant chemotherapy. Goserelin administered after
      cessation of chemotherapy leads to a further improvement and may be equieffective
      as tamoxifen or a combination of both. Data concerning taxane-based and dose
      dense chemotherapy as well as combination of gonadotropin-releasing hormone
      analogs with third-generation aromatase inhibitors are still lacking (ongoing
      suppression of ovarian function, tamoxifen and exemestane, and premenopausal
      endocrine-responsive chemotherapy trials). Moreover, duration of therapy with
      gonadotropin-releasing hormone analogs (2-3 years or longer) is still a matter of
      debate. Palliative endocrine treatment is standard in the first-line therapy of
      patients without life-threatening disease and endocrine-responsive breast cancer.
      Treatment decisions depend upon adjuvant endocrine pretreatment. Clinical data
      regarding ovarian protection by synchronous use of gonadotropin-releasing hormone
      in young breast cancer patients receiving chemotherapy are incoherent.

PMID- 16111460
TI  - Pegfilgrastim: evidence in support of its use with cytotoxic chemotherapy.
AB  - The advent of granulocyte colony-stimulating factor, in particular filgrastim, in
      clinical use more than 10 years ago made a significant impact on the management
      of neutropenia and its complications. More recently, the application of
      pegylation technology has created a second-generation molecule, pegfilgrastim,
      with significantly altered pharmacokinetic properties. This has allowed for a
      once per chemotherapy cycle dosing in contrast to the requirement of daily
      subcutaneous administration for filgrastim. Several randomized trials in
      nonmyeloid malignancies have proven that a fixed dose of pegfilgrastim 6 mg is at
      least equivalent to daily filgrastim therapy. Emerging evidence also suggests
      that pegfilgrastim may be equally employed in the setting of chemotherapy for
      acute myeloid leukemia, dose-dense chemotherapy and peripheral stem cell
      mobilization. If confirmed in subsequent Phase III trials, it is likely that
      pegfilgrastim will eventually succeed filgrastim as the colony-stimulating factor
      of choice in clinical practice.

PMID- 16111463
TI  - Docetaxel in the treatment of breast cancer: current experience and future
      prospects.
AB  - It has become clear over the past 10 years that docetaxel, a semisynthetic taxoid
      antineoplastic agent, is among the most promising compounds to have been
      developed in the 1990s for the treatment of breast cancer. Data indicate that
      this drug became standard therapy in the treatment of patients with metastatic
      disease who have failed anthracycline treatment, and secondarily showed very
      encouraging results in the first-line metastatic setting either in
      monochemotherapy or when docetaxel was combined with an anthracycline. More
      recently, docetaxel also became one of the standard therapies in the adjuvant and
      neoadjuvant settings, and a promising partner for novel biologic therapies.
      Current research is further exploring the effect of docetaxel on outcome of early
      breast cancer in order to fully determine the extent that this chemotherapeutic
      agent will change the natural history of breast cancer.

PMID- 16111465
TI  - Antiangiogenic strategies in hepatocellular carcinoma: current status.
AB  - Hepatocellular carcinoma is a leading cause of cancer death worldwide in both
      adult and pediatric patients. Despite many options, no ideal treatment exists for
      this highly malignant tumor, and management strategies have varied accordingly.
      Angiogenesis, the formation of new blood vessels, is an essential component of
      hepatocellular carcinoma biology. Innovative approaches such as targeting the
      nontransformed, less resistant, tumor-supporting endothelial cells are currently
      under investigation in hepatocellular carcinoma. This review will focus on the
      current knowledge of the pathophysiology of hepatocellular carcinoma
      angiogenesis, as well as the reported data with angiogenesis inhibitors against
      hepatocellular carcinoma.

PMID- 16111462
TI  - Leuprolide acetate given by a subcutaneous extended-release injection: less of a
      pain?
AB  - Androgen deprivation therapy is a mainstay for the treatment of advanced prostate
      cancer. Hormonal therapy commonly consists of injection of gonadotropin hormone
      releasing hormone agonists. Based on the need for improved convenience of
      administration, a novel formulation of leuprolide acetate (Eligard; Atrix
      Laboratories Inc. & Sanofi Aventis) which incorporates a mixture of selected
      polymers and solvents to achieve sustained drug delivery after subcutaneous
      injection, was developed. The US Food and Drug Administration has approved 1-, 3
      , 4- and 6-month formulations of leuprolide acetate. In clinical trials,
      leuprolide acetate achieves sustained suppression of serum testosterone to
      castration levels (< or =50 ng/dl). The adverse-event profile is consistent with
      the effects of testosterone suppression. This novel delivery system in addition
      to the availability of a 6-month formulation of leuprolide acetate, offers
      patients the option of a convenient twice-yearly injection schedule.

PMID- 16111464
TI  - Clinical trials targeting lung cancer with active immunotherapy: the scope of
      vaccines.
AB  - Successful active immunotherapy is expected to be specific and nontoxic. Until
      now, the success of immunotherapy in cancer has been sporadic and unpredictable.
      This has been attributable in part to the lack of a full understanding of the
      mechanistic underpinnings of immune regulation. Furthermore, the lack of
      systematic success of immunotherapy, as argued in this review, stems from failing
      to effectively target tumors such as non-small cell lung cancer. In this review,
      the rationale and design for induction of immunity to non-small cell lung cancer
      and clinical trials of the most important lung cancer vaccines in development are
      discussed.

PMID- 16111466
TI  - Current role of image-guided ablative therapies in lung cancer.
AB  - Lung cancer is the leading cause of cancer-related mortality in the USA. Until
      recently, lung cancer treatment options (dependent upon the tumor grading and
      staging at presentation, and patient comorbidities) included surgical resection
      (lobar or sublobar), chemotherapy and external-beam radiation therapy. While
      these options are still viewed as the primary standard of care, newer minimally
      invasive percutaneous ablative techniques such as radiofrequency ablation,
      microwave ablation and cryoablation are currently being examined as treatment
      alternatives, especially in the setting of the nonsurgical candidate. This review
      will focus on these three distinct thermoablative techniques in the percutaneous
      setting of lung cancer treatment.

PMID- 16111470
TI  - Therapeutic endoscopy and endoscopic ultrasound for gastrointestinal
      malignancies.
AB  - Gastrointestinal endoscopy and endoscopic ultrasound not only provide strategies
      to diagnose and stage malignancy, but also to administer palliative and
      definitive care. Options for anticancer therapy include endoscopic mucosal
      resection, photodynamic therapy, thermal therapy, self-expanding metal stents and
      recently, endoscopic ultrasound-guided therapy, such as intratumoral injection.
      This review summarizes the available endoscopic techniques with a discussion of
      indications and recent clinical data pertaining to gastrointestinal malignancy.
      This review will inform the reader of emerging treatment options and stress the
      importance of incorporating gastroenterologists into the multidisciplinary
      approach in the management of gastrointestinal cancers.

PMID- 16111469
TI  - Current stage-specific chemotherapeutic options in colon cancer.
AB  - Colorectal cancer is one of the most common cancers worldwide. Until recently,
      chemotherapeutic treatment options were limited to various 5-fluorouracil
      leucovorin combinations. However, the last 10 years have seen rapid developments
      in the treatment of colon cancer. These include the introduction of two
      additional chemotherapeutic agents, irinotecan and oxaliplatin. Additional agents
      have been developed, namely the targeted therapies in the form of the monoclonal
      antibodies bevacizumab and cetuximab. The oral forms of chemotherapy (i.e.,
      capecitabine and uracil-tegafur) have been demonstrated to be as efficacious as
      traditional intravenously administered 5-fluorouracil. As a result, the number of
      possible treatment options available to patients has increased dramatically. The
      aim of this review is to report the currently accepted stage-specific
      chemotherapeutic treatment options for colon cancer, the evidence for these
      regimens and future developments.

PMID- 16111467
TI  - DNA methylation: its role in lung carcinogenesis and therapeutic implications.
AB  - A new era in the treatment of malignant diseases has been observed through the
      use of biologic agents targeting growth factor receptors, signaling pathways,
      gene mutations and others. The results have been impressive in some diseases and
      modest in others. The discovery of new targets has expanded our knowledge of
      different mechanisms in tumorigenesis. One of these mechanisms has been DNA
      methylation, which is an important gene transcription regulator. Although the
      role of methylation in lung carcinogenesis is not well understood, there is an
      enormous quantity of evolving data suggesting its critical role in lung cancer.
      In this review, the authors will discuss methylation in lung carcinogenesis and
      its possible clinical implications.

PMID- 16111468
TI  - Angiogenesis, immune system and growth factors: new targets in colorectal cancer
      therapy.
AB  - Colorectal cancer is the second most common malignant human neoplasia. Over
      recent years, many efforts have been performed in order to develop and improve
      therapeutic protocols, and many advances have been accomplished in both the field
      of adjuvant and palliative therapy. Most of the chemotherapic agents currently
      used in the clinical setting are the products of decades of research aimed at
      inhibiting the uncontrolled growth of dysplastic cells. However, new frontiers in
      this field have recently been opened, with the identification of key molecules
      involved in physiologic mechanisms that are of fundamental importance for cancer
      development and progression. Tumor-induced angiogenesis, the cancer-immune system
      crosstalk and the effect of growth factors on dysplastic cells represent new
      fields of investigation for anticancer therapy.

PMID- 16111471
TI  - Preoperative and adjuvant therapies for upper gastrointestinal cancers.
AB  - Survival of esophageal, gastrointestinal junction and gastric cancers is poor
      given that they frequently present with locally advanced or metastatic disease.
      The incidence of gastrointestinal junction adenocarcinoma is increasing whereas
      that of squamous cell carcinoma of the esophagus is decreasing. The accuracy of
      staging has improved with newer diagnostic techniques, including positron
      emission tomography, endoscopic ultrasound and laparoscopy, and this should be
      integrated in prospective Phase III clinical trials evaluating neoadjuvant and
      adjuvant therapies for some esophageal and all gastric carcinomas. For esophageal
      cancer (except for one trial by Walsh and colleagues), four randomized Phase III
      trials comparing preoperative chemoradiation followed by surgery versus surgery
      alone have not shown a survival benefit. Neither have the trials, where
      preoperative chemoradiation followed by surgery, is compared with definitive
      chemoradiation. Nevertheless, it is commonly practiced in the USA and has become
      a preferred combined modality approach. Postoperative chemoradiation is favored
      in the USA for good performance status patients with resected, high-risk gastric
      or gastroesophageal junction carcinoma (more than Stage IA). The UK-MAGIC trial
      results, showing survival benefit with perioperative chemotherapy in operable
      gastric and lower esophageal cancers, probably has an impact on the treatment
      practice of these cancers in Europe and Asia. Promising results from trials
      involving preoperative chemoradiation followed by surgery in gastric cancer
      (pathologic complete response of 20-30%) need to be further evaluated in a Phase
      III setting and compared with postoperative chemoradiation. Active ongoing
      research will help us clarify the role of preoperative and adjuvant therapies in
      esophageal and gastric cancers. The role of molecular profiling is evolving and
      will help us differentiate the responders from the nonresponders.

PMID- 16111473
TI  - Factors increasing local recurrence in breast-conserving surgery.
AB  - From 20-year follow-up results of two pioneering randomized controlled trials
      demonstrating equal survival after mastectomy and breast-conservation therapy,
      recent high-quality, evidence-based clinical practice recommendations have been
      made. Breast-conservation therapy undoubtedly represents substantial progress for
      a better quality of life for women with early-stage breast cancer. However,
      lumpectomy is associated with a substantial proportion, approximately 10-20%, of
      local recurrence in long-term follow-up studies even after accounting for
      postoperative radiotherapy. Risk factors for local failure include margin status,
      young age and an extensive intraductal component. Young age and family history
      strongly suggest the need for genetic testing before initiation of treatment.
      Women with BRCA1 or BRCA2 mutations should be informed about the increased risk
      of contralateral breast cancer and ipsilateral failure after breast-conservation
      therapy. Bilateral mastectomy should also be offered as a treatment option. There
      is controversy over whether current effective adjuvant treatment, including
      chemotherapy and endocrine therapy, beyond appropriate local treatment as surgery
      and radiotherapy, can improve local control. Instead of debate over whether an
      ipsilateral tumor after breast-conservation therapy is local recurrence or a new
      primary cancer by analyzing conflicting data lacking strong evidence, efforts
      should be focused on reducing this risk irrespective of origin. Selecting women
      for breast-conservation therapy and achieving margin control can reduce
      ipsilateral failures.

PMID- 16111472
TI  - Promises and pitfalls in the prediction of antiepidermal growth factor receptor
      activity.
AB  - There is a constant examination of the features that may anticipate or predict
      the likelihood of the clinical benefit that a patient may experience from a given
      therapy. This is especially true in the case of novel targeted therapies, as
      proof-of-principle experimental or pilot analyses are increasingly being embedded
      into clinical protocols. An unprecedented number of significant developments in
      the field of epidermal growth factor receptor-targeted therapy have occurred in
      recent months. This is exemplified by the discovery of activating mutations in
      the catalytic domain of the epidermal growth factor receptor that increase
      sensitivity to antiepidermal growth factor receptor small-molecule inhibitors.
      This review discusses the recent advances and controversies of the different
      approaches to predict the efficacy of antiepidermal growth factor receptor agents
      and the effectiveness of the tools that we are using to evaluate and predict the
      efficacy of epidermal growth factor receptor-targeted drugs and their potential
      pitfalls.

PMID- 16111474
TI  - Influence of the chemistry of conjugation of poly(ethylene glycol) to Hb on the
      oxygen-binding and solution properties of the PEG-Hb conjugate.
AB  - Our recent studies on PEG-Hb [poly(ethylene glycol)-Hb] conjugates generated by
      thiolation-mediated maleimide-chemistry based PEGylation demonstrated that the
      vasoactivity of the PEG-Hb conjugates is a function of the configuration of the
      PEG chains on the surface of the protein and is independent of the PEG/protein
      mass ratio [Manjula, A. G. Tsai, Intaglietta, H.-C. Tsai, Ho, Smith, Perumalsamy,
      Kanika, Friedman and Acharya (2005) Protein J. 24, 133-146]. A Hb conjugated with
      six PEG5k chains (SP-PEG5k)6-Hb, was vasoinactive. In an attempt to understand
      whether the chemistry of conjugation of PEG to Hb has any influence on the
      modulation of its functional and solution properties, we have now generated a new
      hexaPEGylated-Hb, (propyl-PEG5k)6-Hb, by reductive alkylation chemistry. CD
      (circular dichroism) spectral measurements indicated that the overall secondary
      structure of Hb is not adversely influenced upon PEGylation. (Propyl-PEG5k)6-Hb
      exhibited an increased O2 affinity with decreased co-operativity and decreased
      modulation by allosteric effectors comparable with that of (SP-PEG5k)6-Hb,
      although its Cys-93(b) is not derivatized as in the latter. On a molecular mass
      basis, PEG linked to Hb by reductive alkylation increased its COP (colloidal
      osmotic pressure) more efficiently than when linked by thiolation-mediated
      maleimide-chemistry. These results demonstrate that the functional properties of
      PEG-Hb conjugates may be a direct consequence of surface decoration of Hb with
      PEG, but are independent of the site (pattern) and/or the chemistry of
      PEGylation. However the solution properties of PEGylated Hb are influenced by the
      site (pattern) and/or the chemistry of PEGylation and the presence or absence of
      an 'extension arm' between the conjugating site of Hb and the PEG chain.

PMID- 16111475
TI  - The calcium-dependent ATP-Mg/Pi mitochondrial carrier is a target of glucose
      induced calcium signalling in Saccharomyces cerevisiae.
AB  - Sal1p is a mitochondrial protein that belongs to the SCaMC (short calcium-binding
      mitochondrial carrier) subfamily of mitochondrial carriers. The presence of
      calcium-binding motifs facing the extramitochondrial space allows the regulation
      of the transport activity of these carriers by cytosolic calcium and provides a
      new mechanism to transduce calcium signals in mitochondria without the
      requirement of calcium entry in the organelle. We have studied its transport
      activity, finding that it is a carboxyatractyloside-resistant ATP-Mg carrier.
      Mitochondria from a disruption mutant of SAL1 have a 50% reduction in the uptake
      of ATP. We have also found a clear stimulation of ATP-transport activity by
      calcium, with an S(0.5) of approx. 30 microM. Our results also suggest that Sal1p
      is a target of the glucose-induced calcium signal which is non-essential in wild
      type cells, but becomes essential for transport of ATP into mitochondria in yeast
      lacking ADP/ATP translocases.

PMID- 16111476
TI  - Slow thrombin in solution.
AB  - As a tool for understanding biological mechanisms, X-ray crystallography
      possesses unparalleled power to enlighten, resolve controversy and shift a field
      of study on to a secure new paradigm. Thanks largely to developments in
      crystallographic methods, the technique has become accessible to the general
      biochemist and we have thus witnessed an exponential increase in the number of
      protein structures deposited every year. It is now commonplace for several
      structures to be published of the same protein under different crystallization
      conditions, sometimes resulting in conflicting mechanistic interpretations. Such
      a controversy has arisen over thrombin's conformational response to Na+ co
      ordination, and in this issue of Biochemical Journal, De Filippis and colleagues
      put the two structural models of thrombin allostery to the test by returning to
      the techniques of solution biochemistry.

PMID- 16111477
TI  - In vivo evidence of CHIP up-regulation attenuating tau aggregation.
AB  - The carboxyl terminus of heat-shock cognate (Hsc)70-interacting protein (CHIP) is
      a ubiquitin E3 ligase that can collaborate with molecular chaperones to
      facilitate protein folding and prevent protein aggregation. Previous studies
      showed that, together with heat-shock protein (Hsp)70, CHIP can regulate tau
      ubiquitination and degradation in a cell culture system. Ubiquitinated tau is one
      component in neurofibrillary tangles (NFTs), which are a major histopathological
      feature of Alzheimer's disease (AD). However, the precise sequence of events
      leading to NFT formation and the mechanisms involved remain unclear. To confirm
      CHIP's role in suppressing NFT formation in vivo, we performed a quantitative
      analysis of CHIP in human and mouse brains. We found increased levels of CHIP and
      Hsp70 in AD compared with normal controls. CHIP levels in both AD and controls
      corresponded directly to Hsp90 levels, but not to Hsp70 or Hsc70 levels. In AD
      samples, CHIP was inversely proportional to sarkosyl-insoluble tau accumulation.
      In a JNPL3 mouse brain tauopathy model, CHIP was widely distributed but weakly
      expressed in spinal cord, which was the most prominent region for tau inclusions
      and neuronal loss. Protein levels of CHIP in cerebellar regions of JNPL3 mice
      were significantly higher than in non-transgenic littermates. Human tau was more
      highly expressed in this region of mouse brains, but only moderate levels of
      sarkosyl-insoluble tau were detected. This was confirmed when increased insoluble
      tau accumulation was found in mice lacking CHIP. These findings suggest that
      increases in CHIP may protect against NFT formation in the early stages of AD. If
      confirmed, this would indicate that the quality-control machinery in a neuron
      might play an important role in retarding the pathogenesis of tauopathies.

PMID- 16111478
TI  - Lovastatin inhibits the growth and survival pathway of phosphoinositide 3
      kinase/protein kinase B in immortalized rat brain neuroblasts.
AB  - We previously showed that lovastatin, an HMG-CoA reductase inhibitor, suppresses
      cell growth by inducing apoptosis in rat brain neuroblasts. Our aim was to study
      intracellular signalling induced by lovastatin in neuroblasts. Lovastatin
      significantly decreases the phosphoinositide 3-kinase (PI3-K) activity in a
      concentration-dependent manner. Expression of p85 subunit and its association
      with phosphotyrosine-containing proteins are unaffected by lovastatin. Lovastatin
      decreases protein kinase B (PKB)/Akt phosphorylation, and its downstream
      effectors, p70S6K and the eukaryotic initiation factor 4E (eIF4E) regulatory
      protein 1, 4E-BP1, in a concentration-dependent manner, and reduces p70S6K
      expression. Lovastatin effects are fully prevented with mevalonate. Only the
      highest dose of PI3-K inhibitors that significantly reduce PI3-K kinase activity
      induces apoptosis in neuroblasts but to a lower degree than lovastatin. In
      summary, this work shows that treatment of brain neuroblasts with lovastatin
      leads to an inhibition of the main pathway that controls cell growth and
      survival, PI3-K/PKB and the subsequent blockade of downstream proteins implicated
      in the regulation of protein synthesis. This work suggests that inactivation of
      the antiapoptotic PI3-K appears insufficient to induce the degree of neuroblasts
      apoptosis provoked by lovastatin, which must necessarily involve other
      intracellular pathways. These findings might contribute to elucidate the
      molecular mechanisms of some statins effects in the central nervous system.

PMID- 16111480
TI  - Polarized distribution of nucleoside transporters in rat brain endothelial and
      choroid plexus epithelial cells.
AB  - This study investigated mRNA expression and protein localization of equilibrative
      and concentrative nucleoside transporters (ENTs, CNTs) in primary cultures of rat
      brain endothelial cells (RBEC) and rat choroid plexus epithelial cells (RCPEC).
      Reverse transcriptase PCR analysis revealed that RBEC and RCPEC contained mRNA
      for rENT1, rENT2 and rCNT2 and for rENT1, rENT2, rCNT2 and rCNT3, respectively.
      Immunoblotting of membrane fractions of RBEC, fresh RCPEC and primary cultures of
      RCPEC revealed the presence of rENT1, rENT2 and rCNT2 proteins in all samples.
      Measurement of [14C]adenosine uptake into cells grown as monolayers on permeable
      plastic supports revealed a polarized distribution of Na+-dependent adenosine
      uptake in that CNT activity was associated exclusively in membranes of RBEC
      facing the lower chamber (which corresponds to the surface facing the
      interstitial fluid in situ) and in membranes of RCPEC facing the upper chamber
      (which corresponds to the surface facing the cerebrospinal fluid in situ). In
      both RBEC and RCPEC, adenosine uptake from the opposite chambers was Na+
      independent and partially inhibited by nitrobenzylthioinosine, indicating the
      presence of the equilibrative sensitive transporter rENT1.

PMID- 16111479
TI  - Lithium enhances secretion from large dense-core vesicles in nerve growth factor
      differentiated PC12 cells.
AB  - Considerable attention has been focused on the therapeutic role of lithium (Li)
      in bipolar disorders. Although no consensus has emerged, Li presumably influences
      the behavior of neurons that regulate mood and behavior. Using PC12 cells to
      study cellular and molecular actions of Li, we previously reported that Li
      modulates the expression of proteins associated with large dense-core vesicles
      (LDCVs; organelles typically containing monoamines, neuropeptides and other cargo
      proteins). The current investigation indicates that this enhanced expression of
      LDCV proteins correlates with an altered secretory phenotype in Li-treated cells.
      Immunoblotting detects significant increases in the cellular content and
      secretion of the LDCV cargo proteins chromogranin B and secretogranin II.
      Amperometry reveals an increase of spike number elicited by K+-depolarization of
      Li-treated cells but no change of spike amplitude or kinetics. Electron
      microscopy reveals no significant change in LDCV number per unit area in Li
      treated cells. However, there is a significant increase (about 15%) in the
      diameter of LDCVs after Li. Thus, Li induces changes in the properties of LDCVs
      that culminate in augmented regulated secretion in nerve growth factor
      differentiated PC12 cells. These results extend our understanding of Li-dependent
      changes of cellular function that may be germane to the therapeutic action of Li.

PMID- 16111481
TI  - Effect of the degree of ischaemic injury and reoxygenation time on the type of
      myocardial cell death in man: role of caspases.
AB  - BACKGROUND: The importance of apoptosis in the injury sustained by the human
      myocardium during ischaemia and reoxygenation and the underlying mechanisms
      remain unclear. To quantify apoptosis and necrosis induced by simulated
      ischaemia/reoxygenation in the human atrial myocardium, free-hand sections of
      right atrial appendage (n = 8/group) were subjected to 90 minutes simulated
      ischaemia followed by 2, 8 and 24 hours reoxygenation. RESULTS: Apoptosis, as
      assessed by TUNEL, was greater than necrosis after 90 minutes simulated ischaemia
      and 2 hours reoxygenation (35.32 +/- 3.22% vs 13.55 +/- 1.3%; p < 0.05) but
      necrosis was greater than apoptosis by 24 hours reoxygenation (45.20 +/- 2.75% vs
      4.82 +/- 0.79%; p < 0.05). Total caspase activation was similar after 90 minutes
      simulated ischaemia followed by 2 hours and 24 hours reoxygenation (515270 +/-
      99570 U vs 542940 +/- 95216 U; p = NS). However, caspase-3 like activation was
      higher at 2 hours than at 24 hours reoxygenation (135900 +/- 42200 U vs 54970 +/-
      19100 U; p < 0.05). Inhibition of caspase-3 by z.DEVD.fmk (70 nM) almost
      completely abolished apoptosis from 23.26 +/- 2.854% to 0.73 +/- 0.28 % (p <
      0.05), without affecting necrosis. CONCLUSION: Cell death by apoptosis and
      necrosis in the human myocardium subjected to simulated ischaemia/reoxygenation
      depends on the degree of the ischaemic insult and have a different time-course
      with apoptosis happening early during reoxygenation and necrosis becoming more
      important later. Importantly, the apoptosis induced by simulated
      ischaemia/reoxygenation is mainly mediated by activation of caspase-3 but it does
      not affect necrosis.

PMID- 16111482
TI  - Insect sting allergy. A study from 1980 to 2003 of patients who started treatment
      with venom immunotherapy between 1980 and 1998.
AB  - BACKGROUND: Previously we treated patients with insect sting allergy with venom
      immunotherapy (IT) using whole body insect extracts. From 1980 we changed to
      insect venoms. The purpose of this study was to analyse data from the patients in
      order to improve our treatment. METHODS: This is an open, single centre study on
      patients treated with venom IT 14 years or older with a history of a systemic
      allergic reaction to an insect sting, a positive skin prick test (SPT) or a
      positive RAST and willingness to comply with five years of IT. Clinical and
      laboratory data were registered prospectively at the start of IT and after five
      years of treatment until 2003 on patients who started IT between 1980 and 1998.
      Questionnaires were answered in 1989, 1993 and 2003. Statistical analysis was
      done with Pearson's chi square, Fisher's exact or the t-test. RESULTS: Of 315
      patients treated, 44 were given bee, 248 common wasp and 23 both venoms. Of the
      common wasp sting incidents 5.5 % resulted in a severe allergic reaction (SAR)
      during adequate IT and 22% after cessation. Seventy-one per cent of the patients
      carried epinephrine. Precautionary steps were taken by 77% of the patients during
      or after inadequate IT. On or after adequate IT 83% felt completely or
      substantially safe. Surprisingly 29 % of those inadequately treated felt safer
      and 50% were satisfied with having had the opportunity to be treated. The SPT
      became negative in 68% of the wasp allergic patients after five years of adequate
      IT. Increased risk of experiencing SAR to a future sting in wasp allergic
      patients after cessation of adequate IT was significantly associated with a SAR
      due to IT during the rush regimen. SAR due to IT occurred very rarely during
      maintenance dosing. CONCLUSION: Adequate venom IT is very effective while ongoing
      but somewhat less effective after cessation, while inadequate treatment gives
      poor results. More of our patients should complete five years of IT and some
      should continue IT. The type of reaction to IT during incremental dosing may be
      of help in deciding who should continue beyond five years. Maintenance IT may be
      taken over by the general physician.

PMID- 16111483
TI  - Pneumothorax after a clinical breast fine-needle aspiration of a lump in a
      patient with Poland's syndrome.
AB  - We report the first case in the medical literature of a pneumothorax complicating
      fine needle aspiration cytology (FNAC) of a breast lump in a woman with a mild
      form of Poland's syndrome. The pneumothorax was treated conservatively. This is
      the first case of breast FNA-related pneumothorax seen in our clinical practice.
      We believe that the absence of pectoral muscles has increased the risk of this
      complication. We have also diagnosed an incidental screen-detected breast cancer
      affecting the ipsilateral breast in the same patient. We conclude that caution
      should be exercised when performing FNAC of breast lesions in patients with
      Poland's syndrome. The procedure should be preferably performed under image
      guidance in such patients in order to minimise the risk of this complication.

PMID- 16111485
TI  - The significance of glucose, insulin and potassium for immunology and oncology: a
      new model of immunity.
AB  - BACKGROUND: A recent development in critical care medicine makes it urgent that
      research into the effect of hormones on immunity be pursued aggressively. Studies
      have demonstrated a large reduction in mortality as a result of infusion with
      glucose, insulin and potassium. Our work in the oncology setting has led us to
      propose that the principal reason for such an effect is that GIK stimulates
      lymphocytes to proliferate and attack pathogens, sparing the patient the stress
      of infection. That suggestion is based on a new model of immunity that describes
      the effect of hormones on lymphocytes. We hypothesized that the application of
      glucose, insulin, thyroid and potassium would awaken inert tumor infiltrating
      lymphocytes to destroy the tumor. METHODS: The antitumor effect of a thyroxine,
      glucose, insulin, and potassium (TGIK) combination was studied in a series of
      controlled experiments in murine models of tumor progression to assess the
      biologic activity of the formulation, the effect of route of administration, the
      effect on tumor type, and the requirement for insulin in the TGIK formulation.
      RESULTS: Melanoma and colon tumors inoculated with TGIK were significantly
      reduced in size or retarded in growth compared to controls injected with saline.
      I.P. and I.M. injections showed that the formulation had no effect systemically
      at the doses administered. CONCLUSION: We conclude that TGIK has anti-tumor
      activity when administered intratumorally, probably by stimulating lymphocytes to
      attack tumors. This is similar to the effect of GIK on reducing sepsis in
      critical care patients. We suggest that when GIK is administered exogenously, it
      restores immune competence to the critically ill or cancer patient and causes
      destruction of pathogens or tumors, while endogenous resources are devoted to
      repair. This implies that hormonal therapy may be useful in treating various
      other pathologies involving immune suppression, as well as malignancies. We also
      propose research that could bring resolution of the controversy over mechanism
      and point the way to new therapeutic strategies for numerous diseases including
      chronic infections and auto-immune diseases.

PMID- 16111484
TI  - A case report of Merkel cell carcinoma on chronic lymphocytic leukemia:
      differential diagnosis of coexisting lymphadenopathy and indications for early
      aggressive treatment.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is a monoclonal disorder,
      characterized by a progressive proliferation of functionally incompetent B
      lymphocytes. There is increased evidence of association between CLL and skin
      cancers, including the uncommon Merkel cell carcinoma (MCC). CASE PRESENTATION: A
      case report of an 84-year old male, who presented with an aggressively recurrent
      form of MCC on the lower lip, on the background of an 8-year history of untreated
      CLL. During the recurrences of MCC, coexisting regional lymphadenopathy, posed a
      problem in the differential diagnosis and treatment of lymph node involvement.
      Histopathology and immunoistochemistry showed that submandibular lymphadenopathy
      coexisting with the second recurrence of MCC, was due to B-cell small lymphocytic
      lymphoma. The subsequent and more aggressive recurrence of the skin tumor had
      involved the superficial and deep cervical lymph nodes. Surgical excision
      followed by involved field radiation therapy has been proven effective for both
      malignancies. CONCLUSION: MCC has a high incidence of regional lymphadenopathy at
      presentation (12-45%) and even when it arises on the background of chronic
      leukemia, lymphadenopathy at presentation should be managed agressively with
      elective lymph node dissection. We overview the postulated correlation between
      Merkel tumor and CCL, the differential diagnosis of regional lymphadenopathy
      during the recurrences of the skin tumor and the strategies of treatment.

PMID- 16111486
TI  - Prolonged membrane potential depolarization in cingulate pyramidal cells after
      digit amputation in adult rats.
AB  - The anterior cingulate cortex (ACC) plays an important role in higher brain
      functions including learning, memory, and persistent pain. Long-term potentiation
      of excitatory synaptic transmission has been observed in the ACC after digit
      amputation, which might contribute to plastic changes associated with the phantom
      pain. Here we report a long-lasting membrane potential depolarization in ACC
      neurons of adult rats after digit amputation in vivo. Shortly after digit
      amputation of the hind paw, the membrane potential of intracellularly recorded
      ACC neurons quickly depolarized from approximately -70 mV to approximately -15 mV
      and then slowly repolarized. The duration of this amputation-induced
      depolarization was about 40 min. Intracellular staining revealed that these
      neurons were pyramidal neurons in the ACC. The depolarization is activity
      dependent, since peripheral application of lidocaine significantly reduced it.
      Furthermore, the depolarization was significantly reduced by a NMDA receptor
      antagonist MK-801. Our results provide direct in vivo electrophysiological
      evidence that ACC pyramidal cells undergo rapid and prolonged depolarization
      after digit amputation, and the amputation-induced depolarization in ACC neurons
      might be associated with the synaptic mechanisms for phantom pain.

PMID- 16111487
TI  - A randomized trial of mail vs. telephone invitation to a community-based
      cardiovascular health awareness program for older family practice patients
      [ISRCTN61739603].
AB  - BACKGROUND: Family physicians can play an important role in encouraging patients
      to participate in community-based health promotion initiatives designed to
      supplement and enhance their in-office care. Our objectives were to determine
      effective approaches to invite older family practice patients to attend
      cardiovascular health awareness sessions in community pharmacies, and to assess
      the feasibility and acceptability of a program incorporating invitation by
      physicians and feedback to physicians. METHODS: We conducted a prospective
      randomized trial with 1 family physician practice and 5 community pharmacies in
      Dundas, Ontario. Regular patients 65 years or older (n = 235) were randomly
      allocated to invitation by mail or telephone to attend pharmacy cardiovascular
      health awareness sessions led by volunteer peer health educators. A health record
      review captured blood pressure status, monitoring and control. At the sessions,
      volunteers helped patients to measure blood pressure using in-store machines and
      a validated portable device (BPM-100), and recorded blood pressure readings and
      self-reported cardiovascular risk factors. We compared attendance rates in the
      mail and telephone invitation groups and explored factors potentially associated
      with attendance. RESULTS: The 119 patients invited by mail and 116 patients
      contacted by telephone had a mean age of 75.7 (SD, 6.4) years and 46.8% were
      male. Overall, 58.3% (137/235) of invitees attended a pharmacy cardiovascular
      health awareness session. Patients invited by telephone were more likely to
      attend than those invited by mail (72.3% vs. 44.0%, OR 3.3; 95%CI 1.9-5.7; p <
      0.001). CONCLUSION: While the attendance in response to a telephone invitation
      was higher, response to a single letter was substantial. Attendance rates
      indicated considerable interest in community-based cardiovascular health
      promotion activities. A large-scale trial of a pharmacy cardiovascular health
      awareness program for older primary care patients is feasible.

PMID- 16111489
TI  - Computational identification of residues that modulate voltage sensitivity of
      voltage-gated potassium channels.
AB  - BACKGROUND: Studies of the structure-function relationship in proteins for which
      no 3D structure is available are often based on inspection of multiple sequence
      alignments. Many functionally important residues of proteins can be identified
      because they are conserved during evolution. However, residues that vary can also
      be critically important if their variation is responsible for diversity of
      protein function and improved phenotypes. If too few sequences are studied, the
      support for hypotheses on the role of a given residue will be weak, but analysis
      of large multiple alignments is too complex for simple inspection. When a large
      body of sequence and functional data are available for a protein family, mature
      data mining tools, such as machine learning, can be applied to extract
      information more easily, sensitively and reliably. We have undertaken such an
      analysis of voltage-gated potassium channels, a transmembrane protein family
      whose members play indispensable roles in electrically excitable cells. RESULTS:
      We applied different learning algorithms, combined in various implementations, to
      obtain a model that predicts the half activation voltage of a voltage-gated
      potassium channel based on its amino acid sequence. The best result was obtained
      with a k-nearest neighbor classifier combined with a wrapper algorithm for
      feature selection, producing a mean absolute error of prediction of 7.0 mV. The
      predictor was validated by permutation test and evaluation of independent
      experimental data. Feature selection identified a number of residues that are
      predicted to be involved in the voltage sensitive conformation changes; these
      residues are good target candidates for mutagenesis analysis. CONCLUSION: Machine
      learning analysis can identify new testable hypotheses about the
      structure/function relationship in the voltage-gated potassium channel family.
      This approach should be applicable to any protein family if the number of
      training examples and the sequence diversity of the training set that are
      necessary for robust prediction are empirically validated. The predictor and
      datasets can be found at the VKCDB web site.

PMID- 16111488
TI  - Phosphorylation states of cell cycle and DNA repair proteins can be altered by
      the nsSNPs.
AB  - BACKGROUND: Phosphorylation is a reversible post-translational modification that
      affects the intrinsic properties of proteins, such as structure and function. Non
      synonymous single nucleotide polymorphisms (nsSNPs) result in the substitution of
      the encoded amino acids and thus are likely to alter the phosphorylation motifs
      in the proteins. METHODS: In this study, we used the web-based NetPhos tool to
      predict candidate nsSNPs that either introduce or remove putative phosphorylation
      sites in proteins that act in DNA repair and cell cycle pathways. RESULTS: Our
      results demonstrated that a total of 15 nsSNPs (16.9%) were likely to alter the
      putative phosphorylation patterns of 14 proteins. Three of these SNPs (CDKN1A
      S31R, OGG1-S326C, and XRCC3-T241M) have already found to be associated with
      altered cancer risk. We believe that this set of nsSNPs constitutes an excellent
      resource for further molecular and genetic analyses. CONCLUSION: The novel
      systematic approach used in this study will accelerate the understanding of how
      naturally occurring human SNPs may alter protein function through the
      modification of phosphorylation mechanisms and contribute to disease
      susceptibility.

PMID- 16111491
TI  - Glycosaminoglycans modulate C6 glioma cell adhesion to extracellular matrix
      components and alter cell proliferation and cell migration.
AB  - BACKGROUND: Adhesion to extracellular matrix (ECM) components has been implicated
      in the proliferative and invasive properties of tumor cells. We investigated the
      ability of C6 glioma cells to attach to ECM components in vitro and described the
      regulatory role of glycosaminoglycans (GAGs) on their adhesion to the substrate,
      proliferation and migration. RESULTS: ECM proteins (type IV collagen, laminin and
      fibronectin) stimulate rat C6 glioma cell line adhesion in vitro, in a dose
      dependent manner. The higher adhesion values were achieved with type IV collagen.
      Exogenous heparin or chondroitin sulfate impaired, in a dose-dependent manner the
      attachment of C6 glioma cell line to laminin and fibronectin, but not to type IV
      collagen. Dextran sulfate did not affect C6 adhesion to any ECM protein analyzed,
      indicating a specific role of GAGs in mediating glioma adhesion to laminin and
      fibronectin. GAGs and dextran sulfate did not induce C6 glioma detachment from
      any tested substrate suggesting specific effect in the initial step of cell
      adhesion. Furthermore, heparin and chondroitin sulfate impaired C6 cells
      proliferation on fibronectin, but not on type IV collagen or laminin. In
      contrast, both GAGs stimulate the glioma migration on laminin without effect on
      type IV collagen or fibronectin. CONCLUSION: The results suggest that GAGs and
      proteoglycans regulate glioma cell adhesion to ECM proteins in specific manner
      leading to cell proliferation or cell migration, according to the ECM
      composition, thus modulating tumor cell properties.

PMID- 16111492
TI  - Matrix attachment regions as targets for retroviral integration.
AB  - BACKGROUND: The randomness of retroviral integration has been debated for many
      years. Recent evidence indicates that integration site selection is not random,
      and that it is influenced by both viral and cellular factors. To study the role
      of DNA structure in site selection, retroviral integration near matrix attachment
      regions (MARs) was analyzed for three different groups of retroviruses. The
      objective was to assess whether integration near MARs may be a factor for
      integration site selection. RESULTS: Results indicated that MLV, SL3-3 MuLV, HIV
      1 and HTLV-1 integrate preferentially near MARs, specifically within 2-kilobases
      (kb). In addition, a preferential position and orientation relative to the
      adjacent MAR was observed for each virus. Further analysis of SL3-3 MuLV
      insertions in common integration sites (CISs) demonstrated a higher frequency of
      integration near MARs and an orientation preference that was not observed for
      integrations outside CISs. CONCLUSION: These findings contribute to a growing
      body of evidence indicating that retroviral integration is not random, that MARs
      influence integration site selection for some retroviruses, and that integration
      near MARs may have a role in the insertional activation of oncogenes by
      gammaretroviruses.

PMID- 16111493
TI  - Identification of a new family of enzymes with potential O-acetylpeptidoglycan
      esterase activity in both Gram-positive and Gram-negative bacteria.
AB  - BACKGROUND: The metabolism of the rigid bacterial cell wall heteropolymer
      peptidoglycan is a dynamic process requiring continuous biosynthesis and
      maintenance involving the coordination of both lytic and synthetic enzymes. The O
      acetylation of peptidoglycan has been proposed to provide one level of control on
      these activities as this modification inhibits the action of the major endogenous
      lytic enzymes, the lytic transglycosylases. The O-acetylation of peptidoglycan
      also inhibits the activity of the lysozymes which serve as the first line of
      defense of host cells against the invasion of bacterial pathogens. Despite this
      central importance, there is a dearth of information regarding peptidoglycan O
      acetylation and nothing has previously been reported on its de-acetylation.
      RESULTS: Homology searches of the genome databases have permitted this first
      report on the identification of a potential family of O-Acetylpeptidoglycan
      esterases (Ape). These proteins encoded in the genomes of a variety of both Gram
      negative and Gram-positive bacteria, including a number of important human
      pathogens such as species of Neisseria, Helicobacter, Campylobacter, and Bacillus
      anthracis, have been organized into three families based on amino acid sequence
      similarities with family 1 being further divided into three sub-families. The
      genes encoding these proteins are shown to be clustered with Peptidoglycan O
      acetyltransferases (Pat) and in some cases, together with other genes involved in
      cell wall metabolism. Representative bacteria that encode the Ape proteins were
      experimentally shown to produce O-acetylated peptidoglycan. CONCLUSION: The
      hypothetical proteins encoded by the pat and ape genes have been organized into
      families based on sequence similarities. The Pat proteins have sequence
      similarity to Pseudomonas aeruginosa AlgI, an integral membrane protein known to
      participate in the O-acetylation of the exopolysaccaride, alginate. As none of
      the bacteria that harbor the pat genes produce alginate, we propose that the Pat
      proteins serve to O-acetylate peptidoglycan which is known to be a maturation
      event occurring in the periplasm. The Ape sequences have amino acid sequence
      similarity to the CAZy CE 3 carbohydrate esterases, a family previously known to
      be composed of only O-acetylxylan esterases. They are predicted to contain the
      alpha/beta hydrolase fold associated with the GDSL and TesA hydrolases and they
      possess the signature motifs associated with the catalytic residues of the CE3
      esterases. Specific signature sequence motifs were identified for the Ape
      proteins which led to their organization into distinct families. We propose that
      by expressing both Pat and Ape enzymes, bacteria would be able to obtain a high
      level of localized control over the degradation of peptidoglycan through the
      attachment and removal of O-linked acetate. This would facilitate the efficient
      insertion of pores and flagella, localize spore formation, and control the level
      of general peptidoglycan turnover.

PMID- 16111494
TI  - Microglial responses to amyloid beta peptide opsonization and indomethacin
      treatment.
AB  - BACKGROUND: Recent studies have suggested that passive or active immunization
      with anti-amyloid beta peptide (Abeta) antibodies may enhance microglial
      clearance of Abeta deposits from the brain. However, in a human clinical trial,
      several patients developed secondary inflammatory responses in brain that were
      sufficient to halt the study. METHODS: We have used an in vitro culture system to
      model the responses of microglia, derived from rapid autopsies of Alzheimer's
      disease patients, to Abeta deposits. RESULTS: Opsonization of the deposits with
      anti-Abeta IgG 6E10 enhanced microglial chemotaxis to and phagocytosis of Abeta,
      as well as exacerbated microglial secretion of the pro-inflammatory cytokines TNF
      alpha and IL-6. Indomethacin, a common nonsteroidal anti-inflammatory drug
      (NSAID), had no effect on microglial chemotaxis or phagocytosis, but did
      significantly inhibit the enhanced production of IL-6 after Abeta opsonization.
      CONCLUSION: These results are consistent with well known, differential NSAID
      actions on immune cell functions, and suggest that concurrent NSAID
      administration might serve as a useful adjunct to Abeta immunization, permitting
      unfettered clearance of Abeta while dampening secondary, inflammation-related
      adverse events.

PMID- 16111495
TI  - Ribosomal intergenic spacer (IGS) length variation across the Drosophilinae
      (Diptera: Drosophilidae).
AB  - BACKGROUND: The intergenic spacer of the ribosomal genes in eukaryotes (IGS)
      contains duplications of the core transcription promoter. The number of these
      duplicated promoters, as measured by the IGS length, appears to be correlated
      with growth rate and development time in several distantly related taxa. In the
      present study, we examined IGS length variation across a number of species of
      Drosophila to determine the amount of variation in this trait across different
      evolutionary time scales. Furthermore, we compared the usefulness of two methods
      commonly used to determine IGS length: Southern Blot Hybridization (SB) and
      Polymerase Chain Reaction (PCR). RESULTS: Our results show broad variation in IGS
      length across the genus Drosophila, but closely related species had similar IGS
      lengths. Our results also suggest that PCR tends to underestimate the true IGS
      size when the size is greater than 5 kb, and that this degree of underestimation
      is greater as the IGS size increases. CONCLUSION: Broad variation in IGS length
      occurs across large evolutionary divergences in the subfamily Drosophilinae.
      Although average IGS length has been shown to evolve rapidly under artificial
      selection, closely related taxa generally have similar average IGS lengths. Our
      comparison of methods suggests that without previous knowledge of the DNA
      sequence of the IGS and flanking regions, both methods be used to accurately
      measure IGS length.

PMID- 16111496
TI  - Strengthening Medicare: will increasing the bulk-billing rate and supply of
      general practitioners increase access to Medicare-funded general practitioner
      services and does rurality matter?
AB  - BACKGROUND: Recent increases in the bulk-billing rate have been taken as an
      indication that the Federal government's Strengthening Medicare initiative, and
      particularly the bulk-billing incentives, are 'working'. Given the enduring
      geographic differences in the supply of general practitioners (GPs) it is timely
      to reconsider the impact that this increase in the provision of 'free care' will
      have on access to Medicare-funded GP services in rural and urban areas of
      Australia. Utilisation has been modelled as two different stochastic processes:
      the decision to consult and the frequency of consultation. RESULTS: In the
      decision to consult model the supply of FFS GPs is a more important predictor of
      utilisation than the bulk-billing rate. Paradoxically the modelling predicts that
      ceteris paribus increases in either GP supply or the bulk-billing rate appear to
      have perverse effects in some areas by decreasing utilisation. In the frequency
      of consultation model, GP density is not a predictor and increasing the bulk
      billing rate will unambiguously increase the frequency of consultation across all
      areas. In both models, the positive impacts associated with changes in supply and
      cost are constrained outside the inner metropolitan area by reduced geographic
      accessibility to Medicare-funded GP services. The modelling also shows that
      people are more likely to consult a GP in areas of high socioeconomic
      disadvantage, although socioeconomic status is not a predictor of frequency of
      consultation. CONCLUSION: Bulk-billing rates and the supply of FFS GPs are
      important features of the Australian health care system that are, potentially,
      amenable to policy manipulation. The implications of this research are that
      government policies designed to achieve similarity in these characteristics
      across geographic areas will not result in equity of access because they fail to
      address problems caused by geographic inaccessibility in rural and remote areas.
      Attempting to increase bulk-billing rates in some of these areas may, in fact,
      reduce access to FFS GP services.

PMID- 16111497
TI  - High risk of HIV in non-brothel based female sex workers in India.
AB  - BACKGROUND: Heterosexual contact is the most common mode of HIV transmission in
      India that is largely linked to sex work. We assessed the non-use of condoms in
      sex work and with regular sex partners by female sex workers (FSWs), and
      identified its associations that could assist in planning HIV prevention
      programmes. METHODS: Detailed documentation of various aspects of sex work, and
      sexual behaviour with regular sex partners, was done through confidential
      interviews for 6,648 FSWs in 13 districts in the Indian state of Andhra Pradesh.
      Multivariate analysis was done to understand condom non-use with clients.
      RESULTS: 5,010 (75.4%), 1,499 (22.5%), and 139 (2.1%) FSWs were street-, home-,
      and brothel-based, respectively. Of the total 6,648 FSWs, 6,165 (92.7%) had
      penetrative vaginal/anal sex with at least one client in the last 15 days, and of
      these 2,907 (47.2%; 95% CI 41.2-53.2%) reported non-use of condom with at least
      one of her last three clients. Lack of knowledge that HIV could be prevented
      (odds ratio 5.01; 95% CI 4.38-5.73), no access to free condoms (odds ratio 3.45;
      95% CI 2.99-3.98), being street-based as compared with brothel-based (odds ratio
      3.36; 95% CI 1.87-6.04), and no participation in FSW support groups (odds ratio
      2.02; 95% CI 1.50-2.70) were the most significant predictors of condom non-use
      with clients. Other associations included lower social support, lower income, age
      >24 years, illiteracy, and living in medium-size urban or rural areas. Of the
      2582 who had penetrative sex with regular sex partner within the last 7 days,
      2428 (94%; 95% CI 92.1-95.9%) had not used condom at last sex, and 1032 (41.8%)
      had neither used condom consistently with clients nor with regular sex partner.
      CONCLUSION: About half the FSWs do not use condom consistently with their clients
      in this Indian state putting them at high risk of HIV infection. Non-brothel
      based FSWs, who form the majority of sex workers in India, were at a
      significantly higher risk of HIV infection as compared with brothel-based FSWs.
      With their high vulnerability, the success of expansion of HIV prevention efforts
      will depend on achieving and sustaining an environment that enables HIV
      prevention with the non-brothel based FSWs.

PMID- 16111498
TI  - The development of common data elements for a multi-institute prostate cancer
      tissue bank: the Cooperative Prostate Cancer Tissue Resource (CPCTR) experience.
AB  - BACKGROUND: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is a
      consortium of four geographically dispersed institutions that are funded by the
      U.S. National Cancer Institute (NCI) to provide clinically annotated prostate
      cancer tissue samples to researchers. To facilitate this effort, it was critical
      to arrive at agreed upon common data elements (CDEs) that could be used to
      collect demographic, pathologic, treatment and clinical outcome data. METHODS:
      The CPCTR investigators convened a CDE curation subcommittee to develop and
      implement CDEs for the annotation of collected prostate tissues. The draft CDEs
      were refined and progressively annotated to make them ISO 11179 compliant. The
      CDEs were implemented in the CPCTR database and tested using software query tools
      developed by the investigators. RESULTS: By collaborative consensus the CPCTR CDE
      subcommittee developed 145 data elements to annotate the tissue samples
      collected. These included for each case: 1) demographic data, 2) clinical
      history, 3) pathology specimen level elements to describe the staging, grading
      and other characteristics of individual surgical pathology cases, 4) tissue block
      level annotation critical to managing a virtual inventory of cases and
      facilitating case selection, and 5) clinical outcome data including treatment,
      recurrence and vital status. These elements have been used successfully to
      respond to over 60 requests by end-users for tissue, including paraffin blocks
      from cases with 5 to 10 years of follow up, tissue microarrays (TMAs), as well as
      frozen tissue collected prospectively for genomic profiling and genetic studies.
      The CPCTR CDEs have been fully implemented in two major tissue banks and have
      been shared with dozens of other tissue banking efforts. CONCLUSION: The freely
      available CDEs developed by the CPCTR are robust, based on "best practices" for
      tissue resources, and are ISO 11179 compliant. The process for CDE development
      described in this manuscript provides a framework model for other organ sites and
      has been used as a model for breast and melanoma tissue banking efforts.

PMID- 16111500
TI  - Catheter-related septic thrombophlebitis of the great central veins successfully
      treated with low-dose streptokinase thrombolysis and antimicrobials.
AB  - BACKGROUND: Septic thrombophlebitis is an iatrogenic life-threatening disease
      associated with use of central venous devices and intravenous (IV) therapy. In
      cancer patients receiving chemotherapy, vein resection or surgical thrombectomy
      in large central venous lines is time-consuming, can delay administration of
      chemotherapy, and therefore can compromise tumor control. Experience with
      thrombolysis has been published for catheter-related thrombosis but for septic
      thrombosis, this experience is scarce. RESULTS: We describe three patients with
      cancer and septic thrombophlebitis of central veins caused by Staphylococcus
      aureus treated with catheter removal, thrombolysis, and intravenous (IV)
      antibiotics. In our reported cases, an initial bolus of 250,000 international
      units (IU) of streptokinase administered during the first h followed by an
      infusion of 20,000-40,000 IU/h for 24-36 h through a proximal peripheral vein was
      sufficient to dissolve the thrombus. After thrombolysis and parenteral antibiotic
      for 4-6 weeks the septic thrombosis due to Staphylococcus aureus solved in all
      cases. No surgical procedure was needed, and potential placement of a catheter in
      the same vein was permitted. CONCLUSION: Thrombolysis with streptokinase solved
      symptoms, cured infection, prevented embolus, and in all cases achieved complete
      thrombus lysis, avoiding permanent central-vein occlusion.

PMID- 16111499
TI  - Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: baseline
      characteristics and short-term effects of fenofibrate [ISRCTN64783481].
AB  - OBJECTIVE: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD)
      Study is examining the effects of long-term fibrate therapy on coronary heart
      disease (CHD) event rates in patients with diabetes mellitus. This article
      describes the trial's run-in phase and patients' baseline characteristics.
      RESEARCH DESIGN AND METHODS: FIELD is a double-blind, placebo-controlled trial in
      63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on
      CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus.
      Patients were to have no indication for lipid-lowering therapy on randomization,
      but could start these or other drugs at any time after randomization. Follow-up
      in the study was to be for a median duration of not less than 5 years and until
      500 major coronary events (fatal coronary heart disease plus nonfatal myocardial
      infarction) had occurred. RESULTS: About 2100 patients (22%) had some
      manifestation of cardiovascular disease (CVD) at baseline and thus high risk
      status. Less than 25% of patients without CVD had a (UKPDS determined) calculated
      5-year CHD risk of <5%, but nearly all had a 5-year stroke risk of <10%. Despite
      this, half of the cohort were obese (BMI > 30), most were men, two-thirds were
      aged over 60 years, and substantial proportions had NCEP ATP III features of the
      metabolic syndrome independent of their diabetes, including low HDL (60%), high
      blood pressure measurement (41%), high waist measurement (65%), and raised
      triglycerides (52%). After a 6-week run-in period before randomisation with all
      participants receiving 200 mg comicronized fenofibrate, there were declines in
      total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL
      cholesterol (6.5%). CONCLUSION: The study will show the effect of PPAR-alpha
      agonist action on CHD and other vascular outcomes in patients with type 2
      diabetes including substantial numbers with low to moderate CVD risk but with the
      various components of the metabolic syndrome. The main results of the study will
      be reported in late 2005.

PMID- 16111501
TI  - Neuropathic pain develops normally in mice lacking both Na(v)1.7 and Na(v)1.8.
AB  - Two voltage gated sodium channel alpha-subunits, Nav1.7 and Nav1.8, are expressed
      at high levels in nociceptor terminals and have been implicated in the
      development of inflammatory pain. Mis-expression of voltage-gated sodium channels
      by damaged sensory neurons has also been implicated in the development of
      neuropathic pain, but the role of Nav1.7 and Nav1.8 is uncertain. Here we show
      that deleting Nav1.7 has no effect on the development of neuropathic pain. Double
      knockouts of both Nav1.7 and Nav1.8 also develop normal levels of neuropathic
      pain, despite a lack of inflammatory pain symptoms and altered mechanical and
      thermal acute pain thresholds. These studies demonstrate that, in contrast to the
      highly significant role for Nav1.7 in determining inflammatory pain thresholds,
      the development of neuropathic pain does not require the presence of either
      Nav1.7 or Nav1.8 alone or in combination.

PMID- 16111502
TI  - Effectiveness of different methods of health education: a comparative assessment
      in a scientific conference.
AB  - BACKGROUND: Every individual mode of health education has its own merits,
      drawbacks as well as their own sphere of effectiveness. A specific mode of
      communication is more useful in a specific setting on a specific group than
      others. To search for optimum mode of communication for a specific audience is a
      major area of research in health education. The issue of imparting health
      education to a gathering of educated people, representing different fields of
      knowledge has remained a relatively less lighted aspect of health education
      research. In this backdrop this study was initiated for making a comparative
      assessment of different methods of dissemination of health education among
      educated people. METHODS: A cross-sectional interviewer administered
      questionnaire survey was conducted involving 142 randomly selected subjects
      during the last session of a five-day conference having health as main theme when
      the opinion of the delegates regarding different communication methods was asked
      for. Collected data was analyzed not only to find out the optimum mode of
      education dissemination in such a setting but also to find the contribution of
      different factors in the preferences of the study subjects. RESULTS: The
      participants opted more (60%) for focused programs of smaller audience (sectional
      program). In both broad area (main program) and focused area programs
      (sectional), the participants preferred lectures (62% and 65.7% respectively).
      Specific topics were preferred both in lectures (67.6%) and symposia (57.7%). In
      the exhibition, exhibits seemed to be more attractive (62%) than the posters.
      Qualification has emerged to be a contributing factor in peoples' choice towards
      sectional programme and also in their affinity to symposia. Increased age was a
      significant contributor in participants' preference towards specific topics.
      Physical barriers of communication appeared to be a problem in the main program
      as well as in the exhibition. Lack of coherence among the speakers was reported
      (69%) to be a major reason for which symposia was not preferred. CONCLUSION: This
      study concluded that while planning for health education dissemination in an
      educated group a focused programme should be formulated in small groups
      preferably in the form of lectures on specific topics, more so while dealing with
      participants of higher age group having higher educational qualification.

PMID- 16111503
TI  - Exploring cancer register data to find risk factors for recurrence of breast
      cancer--application of Canonical Correlation Analysis.
AB  - BACKGROUND: A common approach in exploring register data is to find relationships
      between outcomes and predictors by using multiple regression analysis (MRA). If
      there is more than one outcome variable, the analysis must then be repeated, and
      the results combined in some arbitrary fashion. In contrast, Canonical
      Correlation Analysis (CCA) has the ability to analyze multiple outcomes at the
      same time. One essential outcome after breast cancer treatment is recurrence of
      the disease. It is important to understand the relationship between different
      predictors and recurrence, including the time interval until recurrence. This
      study describes the application of CCA to find important predictors for two
      different outcomes for breast cancer patients, loco-regional recurrence and
      occurrence of distant metastasis and to decrease the number of variables in the
      sets of predictors and outcomes without decreasing the predictive strength of the
      model. METHODS: Data for 637 malignant breast cancer patients admitted in the
      south-east region of Sweden were analyzed. By using CCA and looking at the
      structure coefficients (loadings), relationships between tumor specifications and
      the two outcomes during different time intervals were analyzed and a correlation
      model was built. RESULTS: The analysis successfully detected known predictors for
      breast cancer recurrence during the first two years and distant metastasis 2-4
      years after diagnosis. Nottingham Histologic Grading (NHG) was the most important
      predictor, while age of the patient at the time of diagnosis was not an important
      predictor. CONCLUSION: In cancer registers with high dimensionality, CCA can be
      used for identifying the importance of risk factors for breast cancer recurrence.
      This technique can result in a model ready for further processing by data mining
      methods through reducing the number of variables to important ones.

PMID- 16111504
TI  - Evaluation of the true precocious puberty rats induced by neonatal administration
      of Danazol: therapeutic effects of nourishing "Yin"-Removing "Fire" Chinese herb
      mixture.
AB  - BACKGROUND: Nourishing "Yin"-Removing "Fire" Chinese Herb Mixture, a traditional
      herb-based formulation, has been successfully used for the management of
      idiopathic true precocious puberty (IPP) for more than thirty years. Precocious
      puberty rat model by neonatal administration of Danazol was used to investigate
      the effects of the herb mixture on the advanced sexual development of the rats,
      and the expression of hypothalamic gonadotropin-releasing hormone (GnRH), which
      is the important regulator for the hypothalamus-pituitary-gonadal axis,
      particularly at puberty. METHODS: Female Sprague-Dawley rats were divided into
      five groups: intact normal (N), IPP model (M), vehicle with no IPP (V), IPP model
      exposed to herb mixture (HM) and IPP model exposed to saline (S). Rats at 5 days
      of age were given a single subcutaneous injection of 300 microgram of Danazol
      dissolved in 25 microliter vehicle of propylene glycol-ethanol (1:1, v/v), to
      establish the precocious puberty model. From the day 15, rats in HM and S groups
      were continuously fed with either Nourishing "Yin"-Removing "Fire" Chinese Herb
      Mixture 2 ml or saline 2 ml, until 3 consecutive regular estrous cycles were
      established. The day of vaginal opening and the day of setup regular estrous
      cycle of the rats were observed. Blood concentration of estrogen was determined
      by radioimmunoassay. Immunohistochemistry and RT-PCR analysis were used to
      explore the expression of GnRH. RESULTS: The day of vaginal opening and first
      estrous showed significant advancement in M compared with N and V (p < 0.05,
      respectively). The blood estrogen level increased significantly in M compared
      with those in other groups (about 28 days of age, at the time of vaginal opening
      in M rats) (p < 0.05, respectively). GnRH cells in rostral medial septum (MS),
      Broca diagonal band nucleus (DBB) and the medial preoptic area (MPOA), were
      calculated. The number in M was less than those in N and V (p < 0.05,
      respectively). The number was significantly higher in HM than that in M (p <
      0.05). The GnRH mRNA expression increased significantly in M compared with that
      in N and V (p < 0.05). CONCLUSION: The true precocious puberty model by neonatal
      administration of Danazol in female rats showed augmented expression of
      hypothalamic GnRH; the Nourishing "Yin"-Removing "Fire" Chinese Herb Mixture down
      regulated the increased GnRH expression, and significantly delayed the sexual
      development of the precocious puberty rat.

PMID- 16111526
TI  - Purification, cDNA cloning, and characterization of ghrelin in channel catfish,
      Ictalurus punctatus.
AB  - The ghrelin peptide and cDNA encoding precursor protein were isolated from the
      stomach of a channel catfish, Ictalurus punctatus. Catfish ghrelin is a 22-amino
      acid peptide with a sequence of GSSFLSPTQKPQNRGDRKPPRV. The third serine residue
      has been modified by n-decanoic acid and unsaturated fatty acids; however, an
      octanoylated form could not be identified. The carboxyl end of the peptide
      possessed an amide structure. A Gly-extended, non-amidated 23-amino acid ghrelin
      (ghrelin-Gly) was also isolated. Real-time quantitative PCR analysis revealed
      high levels of gene expression in the stomach and moderate levels in the pancreas
      and gall bladder. Intraperitoneal (IP) injection of ghrelin increased plasma GH
      levels in the catfish, but the effect of ghrelin-Gly was more potent than that of
      amidated ghrelin. Furthermore, IP injection with both amidated ghrelin and
      ghrelin-Gly caused a significant increase in pituitary GH mRNA expression over a
      3-h period. These results indicate that ghrelin is present in catfish and
      stimulates GH gene expression and GH release in channel catfish.

PMID- 16111527
TI  - Uterine papillary serous carcinoma: what have we learned over the past quarter
      century?

PMID- 16111528
TI  - The management of anemia in the myelodysplastic syndrome.
AB  - How to treat anemia in the myelodysplastic syndrome (MDS) is controversial. Many
      health care systems refuse to fund erythropoietin on grounds of health economics.
      A new paper on the effect of anemia in MDS on cardiac remodeling has suggested
      that a higher treatment threshold level for hemoglobin should be introduced. This
      would have an impact of the calculation of risk/benefits.

PMID- 16111529
TI  - Richter's syndrome--the downside of fludarabine?

PMID- 16111530
TI  - Occupation, hobbies, and acute leukemia in adults.
AB  - Occupational and industrial exposures have been implicated in the etiology of
      leukemia, yet uncertainty remains regarding potential high risk occupations. We
      examined the associations between self-reported occupations and hobbies and acute
      leukemia risk using data from 811 cases and 637 controls participating in a case
      control study in the U.S. and Canada. We found that several occupations may
      increase the risk of acute leukemia, particularly occupations related to
      petroleum products, rubber, nuclear energy, munitions, plastics, and electronics
      manufacturing. Differences were noted according to histological type. Other
      occupations and hobbies were not clearly associated with risk.

PMID- 16111531
TI  - Telomerase activity in myelodysplastic syndromes.
AB  - Myelodysplastic syndromes are clonal hematopoietic stem cell disorders
      characterized by ineffective hematopoiesis and peripheral cytopenias. Telomeres
      are thought to be critical in maintaining normal hematopoiesis. In this study, we
      assessed telomere dynamics in order to obtain further insight into the
      pathogenesis of MDS. We studied telomerase activity (TA) in mononuclear cells
      from peripheral blood (PB) and bone marrow (BM) from patients with
      myelodysplastic syndrome (MDS; n=24), acute myeloid leukemia (AML; n=14), chronic
      myeloid leukemia (CML; n=12) and 11 normal controls using a polymerase chain
      reaction-based telomeric repeat amplification assay. Telomerase activities
      (mean+/-S.D.) were found as 0.199+/-0.09, 0.414+/-0.55, 0.253+/-0.26 and 0.181+/
      0.05 pg/ml in PB mononuclear cells, respectively (P>0.05). Comparison of TA of BM
      mononuclear cells from 19 MDS patients versus 10 BM samples from normal controls
      revealed no significant difference (P=0.3). There was no correlation between the
      levels of TA and clinical and prognostic parameters of the patients with MDS,
      such as degree of anemia, platelet counts on presentation, gender, presence of
      organomegaly, bone marrow fibrosis and BM blast percentages. Patients who had
      higher TA had significantly inferior survival compared with patients who had
      lower TA (P=0.005). Consistent with previous data, our results suggest that in
      patients with MDS, telomerase activity might be insufficient to compensate for
      the telomere shortening. Furthermore, TA might be prognostically important in
      patients with MDS. Measurements of enzymatic activity in association with
      telomere length studies may help to understand the prognostic role of telomere
      dynamics in patients with myelodysplastic syndromes more reliably.

PMID- 16111532
TI  - Immunophenotypic changes induced on human HL60 leukaemia cells by 1alpha,25
      dihydroxyvitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate.
AB  - 1alpha,25-Dihydroxyvitamin D3 (1,25D3) induces HL60 cells to acquire a monocyte
      like phenotype, while cells treated with 12-O-tetradecanoyl phorbol-13-acetate
      (TPA) resemble macrophages. Using a microarray of 82 CD antibodies, 24 cluster of
      differentiation (CD) antigens were detected on HL60 cells. 1,25D3 induced the
      following antigens in decreasing order of the change: CD14, CD11c, CD11b, CD54,
      CD86, CD38 and CD66c, with repression of CD117, CD71, CD95, CD45 and CD64. TPA
      induced the following antigens in decreasing order of the change: CD11c, CD9,
      CD11b, CD54, CD38, CD45RO and CD66c, with repression of CD4, CD117, CD95, CD71
      and CD64. The results presented provide a basis for monitoring differentiation
      therapy of myeloid leukaemias in patients.

PMID- 16111533
TI  - The G-CSF receptor carboxyl terminus, truncated in AML/SCN, is required for
      induction of a Stat5 protease activity.
AB  - Granulocyte colony-stimulating factor (G-CSF) has been shown to stimulate the
      activation of the signal transducer and activator of transcription 5 (Stat5). We
      show here that G-CSF-stimulated activation of Stat5 was attenuated when myeloid
      cells were induced to differentiate with G-CSF. Attenuated activation of Stat5
      correlated with reduced Stat5 protein levels, which was associated with
      upregulation of a Stat5 protease activity. Carboxyl terminal truncation of the G
      CSF receptor or expression of leukemogenic proteins Bcr-Abl and Tel-Jak2
      abolished the upregulation of the Stat5 protease activity by G-CSF. These data
      add to our understanding of the roles of G-CSF and Stat5 in normal granulopoiesis
      and leukemogenesis.

PMID- 16111534
TI  - Mitochondrial gene knockout HL60rho0 cells show preferential differentiation into
      monocytes/macrophages.
AB  - This study compares the differentiation potential of mitochondrial gene knockout
      (rho0) and parental HL60 cells in response to 1.25% dimethylsulfoxide (DMSO) and
      10nM phorbol myristate acetate (PMA). Compared to HL60 cells, undifferentiated
      HL60rho0 cells showed partial monocyte/macrophage differentiation, with increased
      CD11c and CD14 expression, decreased CD71 expression, and weak non-specific
      esterase staining. Differentiation along the monocyte/macrophage pathway (PMA)
      was more pronounced in HL60rho0 than parental HL60 cells with increased CD11c and
      CD14 expression and stronger non-specific esterase staining. DMSO-exposure
      resulted in a poorly differentiated nuclear morphology, small respiratory burst
      and marginal up-regulation of CD15 expression in HL60rho0 cells.

PMID- 16111535
TI  - 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dual-specificity phosphatase
      expression and AML cell survival.
AB  - 12-O-Tetradecanoylphorbol-13-acetate (TPA) is being developed as a therapeutic
      agent by virtue of its being a potent modulator of signal transduction in pre
      clinical models of AML [Strair RK, Schaar D, Goodell L, Aisner J, Chin KV, Eid J,
      et al. Administration of a phorbol ester to patients with hematological
      malignancies: preliminary results from a phase I clinical trial of 12-O
      tetradecanoylphorbol-13-acetate. Clin Cancer Res 2002;8:2512-8]. In this report,
      we identify a subset of primary AML samples that undergoes apoptosis after
      exposure to TPA and demonstrate that TPA-induced cytotoxicity is associated with
      modulation of the ERK signaling pathway. Analysis of mitogen-activated protein
      kinase (MAPK) dual-specificity phosphatases (DUSP), as potential regulators of
      AML cell signaling, indicates that these genes are coordinately regulated and
      rapidly induced by TPA in primary AML cells. Therefore, TPA-induced primary AML
      cytotoxicity is associated with modulation of ERK signaling which may be
      partially mediated by regulation of phosphatase expression.

PMID- 16111536
TI  - Alemtuzumab induced complete remission of therapy-resistant pure red cell
      aplasia.
AB  - Two patients with pure red cell aplasia (PRCA) refractory to anti-thymocyte
      globulin, prednisolone, cyclophosphamide, fludarabine, mitoxantrone,
      dexamethasone and cyclosporine, were treated with alemtuzumab (anti-CD52
      antibody). Case 1, a 35-year-old man with idiopathic PRCA, remitted completely
      with 130 mg of alemtuzumab. Case 2, a 42-year-old man with PRCA due to T-cell
      large granular lymphocyte (T-LGL) leukaemia, achieved complete remission of the
      PRCA with 490 mg of alemtuzumab, although the T-LGL leukaemia responded only
      transiently. There were no significant side effects, and normalization of
      erythropoiesis was durable. Alemtuzumab is active in PRCA that is idiopathic or
      secondary to T-cell lymphoproliferative diseases.

PMID- 16111537
TI  - Hemoglobin level threshold for cardiac remodeling and quality of life in
      myelodysplastic syndrome.
AB  - Treatment of myelodysplastic syndrome (MDS) with epoietin is costly. However,
      cardiac morbidity associated with anemia has not been investigated in MDS. We
      studied this aspect in 39 patients. Echocardiography detected cardiac remodeling
      in 11 of 12 transfusion-dependent versus 13 of 27 transfusion-free patients
      (P=0.017). Hemoglobin independently indicated cardiac hypertrophy (P=0.004); each
      unit increase predicted a 49% reduction in the risk of remodeling confirmed by
      the area under the ROC curve (0.84, P<0.0001). At Hb 10.7 g/dL, sensitivity was
      96% and specificity 64%. Below this level quality of life was poorer. Our results
      suggest early treatment, to be confirmed by future trials.

PMID- 16111538
TI  - HOXA9 expression increases with age in human haemopoietic cells.
AB  - HOXA9 is a transcription factor with a central role in both haemopoiesis and
      leukaemia, and has been extensively studied over the past decade. Most notably,
      high levels of HOXA9 expression in haemopoietic cells is a characteristic feature
      of acute myeloid leukaemia (AML), and indeed may be sufficient in its own right
      to cause this disease. Here, we show that HOXA9 expression changes dramatically
      with age, whereby a uniformly low level of expression during early adulthood is
      replaced by a frequently very high expression in adults over sixty.

PMID- 16111539
TI  - MLL-MLLT10 fusion gene in pediatric acute megakaryoblastic leukemia.
AB  - The occurrence of MLL gene rearrangement in acute megakaryoblastic leukemia (AML
      M7, acute myeloid leukemia, French-American-British type M7) is very rare and
      limited to pediatric age: in particular, MLL-MLLT10 fusion, previously reported
      as characteristic of monocytic leukemia, has been reported in only one case of
      pediatric megakaryoblastic leukemia. We describe the second case with this
      association in light of the few reported cases of AML-M7 with MLL and/or 11q23
      involvement.

PMID- 16111541
TI  - Phase II study of topotecan and cyclophosphamide in patients with relapsed and
      refractory multiple myeloma.

PMID- 16111540
TI  - Ph-Chromosome-positive chronic myeloid leukemia with associated bone marrow
      mastocytosis.
AB  - The concurrent development of chronic myeloid (CML) or myelomonocytic (CMML)
      leukemia in patients with systemic mastocytosis (SM) is a well recognized
      phenomenon. Although the leukemia often resembles CML in morphological and in
      clinical terms, a Ph-Chromosome-positive variant has not been reported in SM so
      far. We here describe a 43-year-old female patient with typical Ph-Chromosome
      positive CML in whom a co-existing bone marrow mastocytosis, a special subvariant
      of SM, was diagnosed. RT-PCR analysis revealed the typical p210 kDa form of
      BCR/ABL in leukemic cells. The diagnosis SM was based on the typical focal
      aggregates of spindle-shaped mast cells (MC) in the bone marrow, expression of
      CD25 in MC, and the c-kit mutation D816V, which was detectable in microdissected
      bone marrow MC, but not in microdissected leukemic cells, suggesting the presence
      of two different (sub)clones of neoplastic cells. Therapy with the BCR/ABL
      targeting drug Imatinib (STI571) resulted in complete cytogenetic remission of
      CML. Together, our case provides further evidence for the biologic diversity of
      leukemias that may occur in patients with SM. The exact knowledge of the
      pathology and target-profile of the associated leukemias in SM have important
      therapeutic implications.

PMID- 16111542
TI  - The chick/quail transplantation model: discovery of the isthmic organizer center.
AB  - This paper summarizes chick/quail transplantation experiments performed in the
      INSERM U106 by Alvarado-Mallart's group from 1989 to 2002. First, it will present
      the various steps leading us to demonstrate that, at stage 10 of Hamburger and
      Hamilton, the avian neuroepithelium is still competent to change its fate
      influenced by environmental inductive factors and that these factors emanate from
      the cerebellar neuroepithelium; then, it will be briefly reported, experiments
      aimed to characterize the genetic cascade involved in the formation of the
      midbrain/hindbrain boundary and the specification of the meso-isthmic-cerebellar
      domain.

PMID- 16111543
TI  - Isthmus organizer for midbrain and hindbrain development.
AB  - Classical transplantation studies showed that the isthmus has an organizing
      activity upon the tectum and cerebellum. Since Fgf8 is expressed in the isthmus
      and mimics functionally isthmic grafts, it is accepted that Fgf8 plays pivotal
      role in the isthmic organizing activity. The fate of brain vesicles is determined
      by the combinations of transcription factors. The neural tube region where Otx2,
      Pax2, and En1 are expressed early on acquires midbrain identity. Pax3/7 forces
      the midbrain to differentiate into tectum. En1/2, Pax2/5, and Fgf8 form a
      positive feedback loop for their expression, thus misexpression of one of these
      molecules turns on the loop and forces presumptive diencephalon to differentiate
      into tectum. The isthmic organizer signal, Fgf8, stabilizes or changes the
      expression of the transcription factors in mid/hindbrain region. A strong Fgf8
      signal activates the Ras-ERK signaling pathway, which in turn activates Irx2 in a
      rostrodorsal part of the hindbrain, and forces this tissue to differentiate into
      cerebellum.

PMID- 16111544
TI  - Specification of the meso-isthmo-cerebellar region: the Otx2/Gbx2 boundary.
AB  - The midbrain/hindbrain (MH) territory containing the mesencephalic and
      isthmocerebellar primordial is characterized by the expression of several
      families of regulatory genes including transcription factors (Otx, Gbx, En, and
      Pax) and signaling molecules (Fgf and Wnt). At earlier stages of avian neural
      tube, those genes present a dynamic expression pattern and only at HH18-20
      onwards, when the mesencephalic/metencephalic constriction is coincident with the
      Otx2/Gbx2 boundary, their expression domains become more defined. This review
      summarizes experimental data concerning the genetic mechanisms involved in the
      specification of the midbrain/hindbrain territory emphasizing the chick/quail
      chimeric experiments leading to the discovery of a secondary isthmic organizer.
      Otx2 and Gbx2 co-regulation could determine the precise location of the MH
      boundary and involved in the inductive events characteristic of the isthmic
      organizer center.

PMID- 16111545
TI  - Modulation of Fgf8 activity during vertebrate brain development.
AB  - In recent years much emphasis has been placed on investigation of the precise
      control of FGF signaling during brain development. Such control is achieved in
      part by regulatory elements that determine the domains and levels of expression
      of genes coding for the diverse FGF ligands via specific molecular signaling
      pathways. There is new knowledge on the operation of such mechanisms in regions
      of the neural tube involved in the correct patterning of adjacent territories
      (known as secondary organizers of neural tube pattern). In the present minireview
      we intend to summarize recent evidence and emerging conclusions on potent
      modulators that govern the activity of Fgf8 signals in the developing vertebrate
      brain, focusing our attention on the best known secondary organizer, the isthmic
      organizer.

PMID- 16111546
TI  - Experimental study of MAP kinase phosphatase-3 (Mkp3) expression in the chick
      neural tube in relation to Fgf8 activity.
AB  - Mitogen-activated protein kinase (MAPK) pathways are well known to be involved in
      signal transduction from extracellular to intracellular compartments in all
      eukaryotes. The activation of this cascade will have an effect on cell
      proliferation, differentiation, and apoptosis. In this study, we describe the
      cloning of the chick Mkp3 gene that is highly homologous to the mammalian gene
      and are both expressed in several embryo regions with demonstrated morphogenetic
      activity. In early developmental stages, Mkp3 and Fgf8 have similar expression
      patterns. Differences in the activation of Mkp3 transcription in the isthmus and
      the repression with FGF receptor inhibition suggest that Fgf8 protein controls
      Mkp3 transcription. Ectopically, expression of Fgf8 protein induces Mkp3 in a
      short period of time in the diencephalon, indicating a positive regulation of
      Mkp3 by Fgf8. Moreover, we show a distinct tissue competence to express Mkp3
      rostrally and caudally to the zona limitans intrathalamica (ZLI).

PMID- 16111547
TI  - Correlation of a chicken stage 4 neural plate fate map with early gene expression
      patterns.
AB  - A number of gene markers are currently claimed to allow positive or negative
      visualization of the early chick neural plate at stages 3d/4, when its fate
      becomes determined. Some markers labeled by various authors as either "neural" or
      "non-neural" indeed show ectodermal expression patterns roughly correlative with
      widespread yet vague ideas on the shape and size of the early neural plate, based
      on previous fate maps. However, for technical reasons, it is not clear how
      precisely these expression patterns correlate with any experimentally determined
      fate boundaries. An eventual mismatch between fate and marker interpretation
      might bear importantly on ideas about gene functions and causal hypotheses in
      issues such as the establishment of the neural/non-neural border or the earliest
      mechanisms of neural regionalization. In this review, we correlated a set of
      epiblastic and mesendodermal gene expression patterns with the novel
      neuroectoderm proportions suggested by our recent fate map of the chick neural
      plate at stages HH 3d/4 [P. Fernandez-Garre, L. Rodriguez-Gallardo, V. Gallego
      Diaz, I.S. Alvarez, L. Puelles, Fate map of the chicken neural plate at stage 4,
      Development 129 (2002) 2807-2822.]. This analysis suggests the existence of
      various nested subregions of the epiblast with boundaries codefined by given sets
      of gene patterns. No gene expression studied reproduces exactly or even
      approximately the entire neural plate shape, leading to a combinatorial
      hypothesis on its specification. This kind of analysis (fate and molecular maps),
      jointly with competence maps, provides the basis for understanding gene functions
      and the mechanisms of neural induction, specification and regionalization.
      Several gene patterns observed are consistent with precocious incipient
      regionalization of the neural plate along the dorsoventral and anteroposterior
      axes.

PMID- 16111548
TI  - Postulated boundaries and differential fate in the developing rostral hindbrain.
AB  - The vertebrate brain is progressively regionalized during development in a
      process whereby a precise spatio-temporal arrangement of gene expression patterns
      and resulting intercellular and intracellular signals drive patterning, growth,
      morphogenesis, and final fates, thus producing ordered species-specific
      differentiation of each territory within a shared morphotype. Before genetic and
      molecular biology tools started to be used to uncover the underlying mechanisms
      that control morphogenesis, knowledge on brain development largely depended on
      descriptive analysis and experimental embryology. The first approach allowed us
      to know how the brain develops but not why. The second provided insights into
      inductive and field histogenetic phenomena, requiring causal explanation. In this
      review, we focused on the regionalization of the rostral hindbrain, defined as
      isthmus plus rhombomere 1, which is the least understood part of the hindbrain.
      We addressed what is known about the formation of boundaries in this area and the
      fate of diverse neuroepithelial portions. We introduced to this end some fate
      mapping data recently obtained in our laboratory. Starting from the background of
      pioneering morphological studies and available fate mapping data, we establish
      correlation with current knowledge about how morphogens, transcription factors,
      or other signaling molecules map onto particular territories, from where they may
      drive morphogenetic interactions that generate final fates step by step.

PMID- 16111549
TI  - Agreement and disagreement among fate maps of the chick neural plate.
AB  - Fate maps are essential to understand embryonic development; they provide a
      background for deducing maps of differential cellular specification in the
      context of other experimental data and molecular expression patterns. Due to its
      accessibility, the chick neural plate has been fate-mapped many times, albeit
      without complete agreement with respect to its shape, extent and fated
      subdivisions. In this review, we first comment about avian neural plate fate maps
      reported since the early period of experimental embryology, referring to the
      different methods followed. We next review a perfected fate-mapping methodology,
      which recently allowed us rather precise delimitation of the chick neural plate
      at stages 3d/4. This leads to a general discussion about the apparent border of
      the neural plate and the prospective main rostrocaudal and longitudinal divisions
      of the neural tube.

PMID- 16111550
TI  - The rostral and caudal boundaries of the diencephalon.
AB  - Knowledge of nature and features of the boundaries between the main neural
      regions seems to be essential to understand the rules of brain regionalization.
      On the light of several current and classical criteria used to define cerebral
      boundaries, we examine the features of the places recognized as rostral and
      caudal boundaries in the developing diencephalon and provide new images about the
      glial features of these boundaries. One demonstrated property of some embryonic
      boundaries is the prevention of the crossing cells in the early ventricular zone
      (clonal restriction), while the intermediate zone seems to lack it. Data
      available so far indicate that the early boundary between diencephalon and
      mesencephalon (d/m) is a clonal restriction limit, but not between diencephalon
      and telencephalon (d/t). Later, while diencephalic nuclei form, cellular
      dispersion does not occur through the alar part of d/m, but it achieves in the
      corresponding d/t alar portion. The relationship between origin, migration, and
      cell-type specification of neural cells is being the object of special attention
      in the telencephalon, where specific cellular fenotipes can migrate to distant
      regions following non-radial routes. Such is the case of most GABAergic
      interneurons of avian and mammalian pallium and oligodendrocytes of the
      forebrain. In this regard, little attention has been devoted to the diencephalon,
      where this type of migration, specially those through the rostral boundary, has
      been reported by different authors. We introduce increasing evidence about non
      conventional neuronal migration in the developing diencephalon and compare the
      reported migratory behavior with respect to both boundaries.

PMID- 16111551
TI  - Functions of ephrin/Eph interactions in the development of the nervous system:
      emphasis on the hippocampal system.
AB  - Ephrins and their Eph receptors are membrane-anchored proteins that have key
      roles in the development of the Central Nervous System. The main characteristics
      of ephrin/Eph interactions are that their effect is mediated by cell-to-cell
      contacts and that they can propagate bidirectional signals downstream of the
      ligand-receptor complex. These characteristics make ephrins and Eph receptors
      critical cues in the regulation of migrating cells or axons, and in the
      establishment of tissue patterns and topographic maps in distinct regions of the
      developing brain. In addition, ephrins and Eph receptors regulate synapse
      formation and plasticity. These roles would be promoted by complementary gradual
      expression of receptors and ligands in the neurons involved. Although,
      historically, ephrins and Eph receptors have been considered as repulsion signals
      through barriers or gradients, new evidence indicates that they may be both
      inhibitory and permissive/active cues depending on expression levels. The
      expression of distinct ligands and receptors in the developing and mature
      hippocampus suggests that these proteins are involved in distinct processes
      during the development and maturation of the hippocampal region. In fact, recent
      studies have shown that ephrin/Eph signaling participates in the formation of the
      layer-specific patterns of hippocampal afferents, in synaptogenesis and in
      plasticity. Therefore, ephrin/Eph interactions should be considered a crucial
      system in the development and maturation of the brain regions, including the
      hippocampus.

PMID- 16111552
TI  - The molecular orchestra of the migration of oligodendrocyte precursors during
      development.
AB  - During development of the central nervous system (CNS), postmitotic cells
      (including neurons and myelin-generating cells, the oligodendrocytes) migrate
      from the germinal areas of the neural tube where they originate to their final
      destination sites. The migration of neurons during development has been
      extensively studied and has been the topic of detailed reviews. The migration of
      oligodendrocyte precursor cells (OPCs) is also an extremely complex and precise
      event, with a widespread migration of OPCs across many regions to colonize the
      entire CNS. Different mechanisms have been shown to direct the migration of OPCs,
      among them contact-mediated mechanisms (adhesion molecules) and long-range cues
      (chemotropic molecules). This review provides a detailed overview and discussion
      of the cellular and molecular basis of OPCs migration during development. Because
      it has been shown that neuronal and oligodendroglial lineages share some of these
      mechanisms, we briefly summarize similarities and differences between these two
      types of neural cells. We also summarize the changes in the normal migration of
      OPCs during development that would be relevant for different neurological
      diseases (including demyelinating diseases, such as multiple sclerosis, and glial
      cancers). We also examine the relevance of these migratory properties of the
      oligondendrocytic cell lineage for the repair of neural damage.

PMID- 16111553
TI  - Morphogens as growth cone signalling molecules.
AB  - Morphogen signalling among cells is one of the most important mechanisms
      underlying the progressive patterning of embryos. Members of the hedgehog (Hh),
      wingless (Wnt), transforming growth factor-beta (TGFbeta), and fibroblast growth
      factor (Fgf) families of extracellular signalling molecules act as morphogens.
      Recent studies have demonstrated that members of these four families of proteins,
      secreted by well-characterised organiser centres in the central nervous system
      (CNS) as floor plate or midbrain-hindbrain boundary, are reused at later
      developmental stages to control axon growth. Here, we have summarised the
      evidence for this novel idea with a particular emphasis on those related to Shh
      and Wnt signalling-the object of some works in our laboratory.

PMID- 16111554
TI  - Development of precerebellar nuclei: instructive factors and intracellular
      mediators in neuronal migration, survival and axon pathfinding.
AB  - The precerebellar system provides an interesting model to study tangential
      migrations. All precerebellar neurons (PCN) are generated in the most alar part
      of the hindbrain in a region called rhombic lip. PCN first emit a leading process
      and then translocate their nuclei inside it, a mechanism called nucleokinesis. In
      the past few years, molecular cues that could affect those processes have been
      investigated, with a special care on: (i) the identification of extrinsic factors
      directing cell migration and axon elongation as well as neuronal survival during
      development; (ii) intracellular reorganizations of the cytoskeleton during
      nucleokinesis in response to chemotropic factors. The signaling cascades,
      including regulators of actin and microtubule cytoskeleton, in response to
      diffusible guidance factors have raised an increasing attention. We will here
      review the role of guidance cues involved in PCN migration in particular netrin
      1, Slit and Nr-CAM. We will also consider Rho-GTPases that have been proposed to
      mediate axon outgrowth and neuronal migration, especially in response to netrin
      1, and which may act as a relay between extracellular signals and intracellular
      remodeling. Recent findings from in vitro pharmacological inhibition of various
      Rho-GTPases and over-expression of effectors bring molecular cues that, in
      accordance with anatomical data, fit the idea that nucleokinesis and axon
      outgrowth are not strictly coupled events during PCN migration.

PMID- 16111555
TI  - Naturally occurring neuronal death during the postnatal development of Purkinje
      cells and their precerebellar afferent projections.
AB  - Naturally occurring neuronal death plays a substantial developmental role in the
      building of the neural circuitries. The neuronal death caused by different
      cerebellar mutations is mostly of an apoptotic nature. Apart from the identity of
      the intrinsic mechanisms of the mutations, adult cerebellar mutants are a
      powerful tool to causally study the development of the cerebellar connectivity.
      Thus, studies on adult cerebellar neuronal cell death occurring in mouse mutants
      elucidate: (i) the dependence of the postsynaptic neurons on their partners, (ii)
      the 'en cascade' postsynaptic transneuronal degeneration after target
      deprivation, and (iii) the close relationship between the molecular modular
      organization of the cerebellar cortex and dying Purkinje cells. Neuronal cell
      death has been extensively studied in developing olivocerebellar system. However,
      less data are available on the occurrence of naturally occurring neuronal death
      during the in vivo normal development of the Purkinje cells and the mossy fiber
      system neurons. The developmental role of neuronal death during the establishment
      and refinement of the olivocerebellar projection is currently discussed.
      Moreover, the occurrence of neuronal death during the development of the basilar
      pontine nuclei and its role in the acquisition of the adult pontocerebellar
      projection is still poorly understood. In the present review, we correlate the
      dates of Purkinje cells death with the inferior olivary and basilar pontine
      neuronal apoptosis, discussing their developmental relationships during the
      elaboration of the fine-grained maps of the cerebellar afferent connections.

PMID- 16111556
TI  - Different pontine projections to the two sides of the cerebellum.
AB  - This study analyzed the projections of the basilar pontine nuclei (BPN) and of
      the nucleus reticularis tegmenti pontis (NRTP) to the two sides of the cerebellum
      in the rat. It showed that the two sides of the cerebellar cortex were innervated
      by different percentages of BPN (about 82% of the cells project to the
      contralateral cortex and 18% to the ipsilateral) and NRTP cells (some 60% project
      to the contralateral cortex and 40% to the ipsilateral). In comparison to
      projections traced to the cortex, only a few fibers were traced to the nuclei of
      the same animals. Most of the projections of the BPN to the cerebellar nuclei
      were traced to the lateralis and posterior interpositus nucleus of the
      contralateral side (95%), while a few were traced to homologous nuclei of the
      ipsilateral side (5%). Thus, the BPN principally control the activity of the
      contralateral cerebellum, with a much less important control over the activity of
      the ipsilateral cerebellum. Vice versa, the NRTP, which project to the lateralis,
      interpositus, and medialis nuclei of the two sides, with percentages (64% contra-
      and 36% ipsilateral) similar to those reported for the projections to the cortex,
      is more concerned in the bilateral control of the cerebellum, although with a
      moderate contralateral prevalence. The fact that projections of the BPN were
      principally traced to the contralateral nuclei, from which the efferent
      projection fibers from the cerebellum originate, suggests that the BPN are
      principally involved in the motor control of the contralateral body. Conversely,
      the bilateral projections of the NRTP to the cerebellar nuclei suggest that the
      NRTP is mainly involved in bilateral motor activities. The comparison of the
      projections to the cortex and nuclei of the cerebellum of single animals supports
      the co-existence of coupled (i.e., projections to the cortex and the
      corresponding nuclei) and uncoupled (i.e., projections to the cortex but not to
      the nuclei) projection patterns, from both the BPN and the NRTP. These features
      of the pontocerebellar projections open new vistas on the functional architecture
      of this pathway.

PMID- 16111557
TI  - Injury reactive myelin/oligodendrocyte-derived axon growth inhibition in the
      adult mammalian central nervous system.
AB  - Myelin inhibition is considered a constitutive, static, repulsive barrier not
      reactive to a central nervous system (CNS) lesion. However, recent evidence
      underlines the existence of considerable add-on axon growth inhibition upon CNS
      injury. This postlesional, reactive myelin/oligodendrocyte-derived inhibition
      will require the development of novel screening approaches and therapeutic
      reagents to promote axonal regeneration.

PMID- 16111558
TI  - Cell death and axon regeneration of Purkinje cells after axotomy: challenges of
      classical hypotheses of axon regeneration.
AB  - Although adult mammalian neurons are able to regenerate their axons in the
      peripheral nervous system under certain conditions, they are not able to do it in
      the central nervous system. The environment surrounding the severed axons appears
      to be a key factor for axon regeneration. Many studies aiming to enhance axon
      regeneration in the CNS of adult mammals have successfully manipulated this
      environment by adding growth permissive molecules and/or neutralizing growth
      inhibitory molecules. In both cases, the number of axons able to regenerate was
      low and the different neuronal populations were not equal in their regenerative
      response, suggesting that manipulation of the environment is not always
      sufficient. This is particularly well illustrated in the cerebellar system, in
      which axotomized inferior olivary neurons regenerate when confronted with a
      permissive environment, whereas mature Purkinje cells do not. The intrinsic
      ability of a neuron to regenerate its axon is generally correlated with the
      intensity of its reaction to axotomy (expression of molecules, probability to
      die). Furthermore, molecules such as GAP-43 (growth-associated molecule) and c
      Jun are involved in both axon regeneration and cell death suggesting that these
      two processes are linked. Surprisingly, Purkinje cells lose their capacity to
      regenerate their axon (even in the absence of myelin) during development before
      losing their capacity to react to an axotomy by cell death. These results
      emphasize the different reactions to axotomy between neuron types and underline
      that in Purkinje cells, the two cell decisions (axon regeneration and cell death)
      are differently regulated and therefore not part of the same signaling pathway.

PMID- 16111559
TI  - Cerebellar grafting in the oculomotor system as a model to study target influence
      on adult neurons.
AB  - In the last decades, there have been many efforts directed to gain a better
      understanding on adult neuron-target cell relationships. Embryonic grafts have
      been used for the study of neural circuit rewiring. Thus, using several donor
      neuronal tissues, such as cerebellum or striatum, developing grafted cells have
      been shown to have the capability of substituting neural cell populations and
      establishing reciprocal connections with the host. In addition, different lesion
      paradigms have also led to a better understanding of target dependence in
      neuronal cells. Thus, for example, axotomy induces profound morphofunctional
      changes in adult neurons, including the loss of synaptic inputs and discharge
      alterations. These alterations are probably due to trophic factor loss in
      response to target disconnection. In this review, we summarize the different
      strategies performed to disconnect neurons from their targets, and the effects of
      target substitution, performed by tissue grafting, upon neural properties. Using
      the oculomotor system-and more precisely the abducens internuclear neurons-as a
      model, we describe herein the effects of disconnecting a population of central
      neurons from its natural target (i.e., the medial rectus motoneurons at the
      mesencephalic oculomotor nucleus). We also analyze target-derived influences in
      the structure and physiology of these neurons by using cerebellar embryonic
      grafts as a new target for the axotomized abducens internuclear neurons.

PMID- 16111560
TI  - Neuronal replacement and integration in the rewiring of cerebellar circuits.
AB  - Repair of CNS injury or degeneration by cell replacement may lead to significant
      functional recovery only through faithful reconstruction of the original
      anatomical architecture. This is particularly relevant for point-to-point
      systems, where precisely patterned connections have to be re-established to
      regain adaptive function. Despite the major interest recently drawn on cell
      therapies, little is known about the mechanisms and the potentialities for
      specific integration of new neurons in the mature CNS. Major findings and
      concepts about this issue will be reviewed here, with special focus on work
      dealing with the Purkinje cell transplantation in the rodent cerebellum. These
      studies show that the adult CNS may provide some efficient information to direct
      cell engraftment and process outgrowth. On their side, immature cells may be able
      to induce adaptive changes in their adult partners to facilitate their
      incorporation in the recipient network. Despite the rather high degree of
      specific integration achieved in several different CNS regions, these processes
      are usually defective and long-distance connections are not rewired. Thus,
      although some potentialities for cell replacement exist in the mature CNS, full
      incorporation of new neurons in adult circuits is rarely observed. Indeed,
      intrinsic mechanisms for growth control as well as injury-induced changes in the
      properties and architecture of the nervous tissue contribute to hamper repair
      processes. As a consequence, crucial to obtain successful cell replacement and
      integration in the mature CNS is a deep understanding of the basic biological
      mechanisms that regulate the interactions between newly added elements and the
      recipient environment.

PMID- 16111561
TI  - Cells of the sympathoadrenal lineage: biological properties as donor tissue for
      cell-replacement therapies for Parkinson's disease.
AB  - Sympathoadrenal (SA) cell lineage encompasses neural crest derivatives such as
      sympathetic neurons, small intensely fluorescent (SIF) cells of sympathetic
      ganglia and adrenal medulla, and chromaffin cells of adrenal medulla and extra
      adrenal paraganglia. SA autografts have been used for transplantation in
      Parkinson's disease (PD) for three reasons: (i) as autologous donor tissue avoids
      graft rejection and the need for immunosuppressant therapy, (ii) SA cells express
      dopaminotrophic factors such as GNDF and TGFbetas, and (iii) although most of SA
      cells release noradrenaline, some of them are able to produce and release
      dopamine. Adrenal chromaffin cells were the first SA transplanted cells in both
      animal models of PD and PD patients. However, these autografts have met limited
      success because long-term cell survival is very poor, and this approach is no
      longer pursued clinically. Sympathetic neurons from the superior cervical
      ganglion have been also grafted in PD animal models and PD patients. Poor
      survival into brain parenchyma of grafted tissue is a serious disadvantage for
      its clinical application. However, cultured sympathetic cell grafts present a
      better survival rate, and they reduce the need for levodopa medication in PD
      patients by facilitating the conversion of exogenous levodopa. SA extra-adrenal
      chromaffin cells are located on paraganglia (i.e., the Zuckerkandl's organ), and
      have been used for grafting in a rodent model of PD. Preliminary results indicate
      that long-term survival of these cells is better than for other SA cells,
      exerting a more prolonged restorative neurotrophic action on denervated host
      striatum. The ability of SA extra-adrenal cells to respond to hypoxia,
      differently to SA sympathetic neurons or adrenal medulla cells, could explain
      their good survival rate after brain transplantation.

PMID- 16111562
TI  - Role of nitric oxide in subventricular zone neurogenesis.
AB  - A possible role of nitric oxide (NO) in adult neurogenesis has been suggested
      based on anatomical findings showing that subventricular zone (SVZ) neuroblasts
      are located close to NO-producing cells, and on the known antiproliferative
      actions of NO in many cell types. Experiments have been performed in rodents with
      systemic and intracerebroventricular administrations of the NO synthase (NOS)
      inhibitor L-NAME. NOS inhibition leads to significant increases in the number of
      proliferating cells in the SVZ and olfactory bulb (OB). NO exerts its cytostatic
      action preferentially on the cell population expressing nestin but not betaIII
      tubulin, which may correspond to the type C cells described in the SVZ. The
      negative effect of NO on SVZ cell proliferation has also been confirmed in SVZ
      primary cultures. An inhibition of the tyrosine kinase activity of the epidermal
      growth factor receptor (EGFR) is described as one of the molecular mechanisms
      responsible for the antiproliferative effect of NO in SVZ cells. Biochemical data
      supporting this conclusion has been obtained using the neuroblastoma cell line
      NB69, which endogenously expresses the EGFR. In these cells, the antimitotic
      action of NO occurs upon inhibition of the EGFR tyrosine phosphorylation,
      probably by a direct S-nitrosylation of the receptor. The latest published
      reports on NO and neurogenesis indicate that NO physiologically participates in
      the control of adult neurogenesis by modulating the proliferation and fate of the
      SVZ progenitor cells. These effects might be partially due to a direct inhibition
      of the EGFR by S-nitrosylation.

PMID- 16111563
TI  - Firing activities of identified posterior interpositus nucleus neurons during
      associative learning in behaving cats.
AB  - On the basis of stimulation and permanent or transient lesions of putatively
      involved structures, and using transgenic mice with defective functional
      circuits, it has been proposed that cerebellar cortex and/or nuclei could be the
      sites where classically conditioned nictitating membrane/eyelid responses are
      acquired and stored. Here, we review recent information regarding the electrical
      activities of deep cerebellar nuclei neurons recorded during the performance of
      reflex and acquired eyeblinks. In particular, the rostral pole of the
      dorsolateral region of the posterior interpositus nucleus contains neurons
      significantly related to reflexively evoked and classically conditioned eyelid
      responses. Thus, type A interpositus neurons increase their discharge rate during
      eyelid movements, modulating it depending upon eyelid motorics. In contrast, type
      B neurons decrease their firing, even to a stop, during the same eyelid
      responses. However, as these changes in firing start after the onset of eyelid
      conditioned responses (CRs), and because they do not seem to encode eyelid
      position and velocity during the CR, the interpositus nucleus cannot be
      conclusively considered the site where eyelid learned responses are generated and
      stored. Additional microstimulation and pharmacological blockage of the recorded
      sites support the suggestion that posterior interpositus neurons contribute to
      the enhancement of CRs. Moreover, interpositus neurons probably contribute to the
      proper damping of newly acquired eyelid responses. The contributing role of other
      neuronal centers and circuits related to the eyelid motor system are also
      discussed.

PMID- 16111564
TI  - Changes during the postnatal development in physiological and anatomical
      characteristics of rat motoneurons studied in vitro.
AB  - The postnatal maturation of rat brainstem (oculomotor and hypoglossal nuclei) and
      spinal motoneurons, based on data collected from in vitro studies, is reviewed
      here. Membrane input resistance diminishes with age, but to a greater extent for
      hypoglossal than for oculomotor motoneurons. The time constant of the membrane
      diminishes with age in a similar fashion for both oculomotor and hypoglossal
      motoneurons. The current required to reach threshold (rheobase) decreases in
      oculomotor motoneurons, in contrast with the increase observed in hypoglossal
      motoneurons. The depolarization voltage required to generate an action potential
      also diminishes in oculomotor motoneurons, whereas it remains constant in
      hypoglossal motoneurons. A membrane potential rectification (sag) appears in
      response to negative current steps, hyperpolarizing brainstem motoneurons more
      than 20 mV relative to the rest. This membrane response is more frequent in adult
      motoneurons. The durations of the action potential and its medium
      afterhyperpolarization (mAHP) decrease with postnatal development in all
      motoneurons studied, although the shortening of mAHP is more evident in
      oculomotor motoneurons. A rise in firing rate for all motoneurons with age is
      universal; this trend is also more pronounced in oculomotor motoneurons.
      Developing motoneurons exhibit a postinhibitory rebound depolarization that is
      capable of triggering an action potential or a short burst of spikes. This
      phenomenon is voltage-dependent and requires less of a membrane hyperpolarization
      to elicit an action potential in adult than in neonatal cells. In all developing
      brainstem and spinal motoneurons, the adult somal size is reached within the
      newborn period, although their dendrites continue to elongate. In summary, input
      resistance, time constant, and durations of action potential and mAHP decrease,
      while the frequency of sag and postinhibitory rebound, as well as the motoneuron
      firing rate and dendritic length, increase with postnatal age. These trends are
      universal to all the motoneuronal populations studied; however, the extent of
      these changes differs for each motoneuronal pool. A further distinction is
      evident in the inconsistent age-dependent change in rheobase and depolarization
      voltage for the two brainstem motoneuron nuclei.

PMID- 16111565
TI  - Involvement of the optic tectum and mesencephalic reticular formation in the
      generation of saccadic eye movements in goldfish.
AB  - The circuitry and physiological properties underlying saccadic eye movement
      generation have been studied mainly in monkeys and cats. By contrast, current
      knowledge in nonmammalian species is rather scarce. We review here some of our
      recent findings about the involvement of the optic tectum and mesencephalic
      reticular formation in the generation of saccades in goldfish. Electrical
      microstimulation of the optic tectum evokes contraversive saccadic eye movements.
      In goldfish, as in mammals, the amplitude and direction of saccades are encoded
      in a spatial topographical map. In addition, there are some areas that have
      evolved, such as the extreme anteromedial tectal zone, whose activation yields
      eye convergence. Injections of the bidirectional tracer biotin dextran amine
      within functionally identified sites of the tectum provide reciprocal, site
      dependent connectivity with different downstream structures. Of these structures,
      the major tectofugal target is the mesencephalic reticular formation. In
      goldfish, as in mammals, the mesencephalic reticular formation and optic tectum
      establish reciprocal connections at regional and neuronal levels which support
      the presence of feedback circuits. Electrical microstimulation demonstrates that
      the mesencephalic reticular formation can be functionally parceled-the rostral
      part is linked to vertical saccades, while the caudal part is related with
      horizontal ones. Finally, these zones are also differently connected to the optic
      tectum. From these data, we conclude that the involvement of the optic tectum and
      mesencephalic reticular formation in eye movement generation in goldfish is
      similar to that reported in cats and monkeys.

PMID- 16111566
TI  - Calcium pumps in the central nervous system.
AB  - Two families of Ca2+ transport ATPases are involved in the maintenance of Ca2+
      homeostasis in the nervous system, the plasma membrane Ca2+-ATPase that pumps
      Ca2+ to the extracellular medium and the intracellular sarco/endoplasmic
      reticulum Ca2+-ATPase that transports Ca2+ from the cytosol to the endoplasmic
      reticulum. Both types of calcium pumps show precise regulatory properties and
      they are localized in specific subcellular regions. In this review, we describe
      the functional and regulatory properties of both families of calcium pumps, their
      distribution in nerve cells, and their involvement in neurological disorders. The
      functional characterization of neuronal calcium pumps is very important in order
      to understand the biochemical processes involved in the maintenance of
      intracellular calcium in synaptic terminals.

PMID- 16111567
TI  - Fusion pore regulation of transmitter release.
AB  - During the last decade a wealth of new information about the properties of the
      exocytotic fusion pore is changing our current view of exocytosis. The exocytotic
      fusion pore, a necessary stage before the full merging of the vesicle membrane
      with the plasma membrane, is becoming a key cellular structure that might
      critically control the amount of neurotransmitter released into the synaptic
      cleft and that can be subjected to control by second messengers and
      phosphorylated proteins. Fusion pores form, expand to fully merge membranes, or
      can close leaving an intact and identical synaptic vesicle in place for a new
      round of exocytosis. Transient formation of fusion pores is the mechanistic
      representation of the "kiss-and-run" hypothesis of transmitter release and offers
      new alternatives for synaptic vesicle recycling besides to the classical
      mechanism mediated by clathrin coat endocytosis. For vesicle recycling transient
      fusion pores ensures a fast mechanism for maintaining an active pool of synaptic
      vesicles. The size reached by transient fusion pores and the time spent on the
      open state can determine the release of subquantal synaptic transmission, which
      could be a mechanism of synaptic potentiation. In this review we will described
      the electrophysiological and fluorescence methods that contribute to further
      explore the biophysical properties of the exocytotic fusion pore and the relevant
      experiments obtained by these methods.

PMID- 16111568
TI  - National Residency Matching Program results for radiation oncology, 2005 update.

PMID- 16111569
TI  - Anemia, tumor hypoxemia, and the cancer patient.
AB  - PURPOSE: To review the impact of anemia/tumor hypoxemia on the quality of life
      and survival in cancer patients, and to assess the problems associated with the
      correction of this difficulty. METHODS: MEDLINE searches were performed to find
      relevant literature regarding anemia and/or tumor hypoxia in cancer patients.
      Articles were evaluated in order to assess the epidemiology, adverse patient
      effects, anemia correction guidelines, and mechanisms of hypoxia-induced cancer
      cell growth and/or therapeutic resistance. Past and current clinical studies of
      radiosensitization via tumor oxygenation/hypoxic cell sensitization were
      reviewed. All clinical studies using multi-variate analysis were analyzed to show
      whether or not anemia and/or tumor hypoxemia affected tumor control and patient
      survival. Articles dealing with the correction of anemia via transfusion and/or
      erythropoietin were reviewed in order to show the impact of the rectification on
      the quality of life and survival of cancer patients. RESULTS: Approximately 40
      64% of patients presenting for cancer therapy are anemic. The rate of anemia
      rises with the use of chemotherapy, radiotherapy, and hormonal therapy for
      prostate cancer. Anemia is associated with reductions both in quality of life and
      survival. Tumor hypoxemia has been hypothesized to lead to tumor growth and
      resistance to therapy because it leads to angiogenesis, genetic mutations,
      resistance to apoptosis, and a resistance to free radicals from chemotherapy and
      radiotherapy. Nineteen clinical studies of anemia and eight clinical studies of
      tumor hypoxemia were found that used multi-variate analysis to determine the
      effect of these conditions on the local control and/or survival of cancer
      patients. Despite differing definitions of anemia and hypoxemia, all studies have
      shown a correlation between low hemoglobin levels and/or higher amounts of tumor
      hypoxia with poorer prognosis. Radiosensitization through improvements in tumor
      oxygenation/hypoxic cell sensitization has met with limited success via the use
      of hyperbaric oxygen, electron-affinic radiosensitizers, and mitomycin.
      Improvements in tumor oxygenation via the use of carbogen and nicotinamide,
      RSR13, and tirapazamine have shown promising clinical results and are all
      currently being tested in Phase III trials. The National Comprehensive Cancer
      Network (NCCN) guidelines recommend transfusion or erythropoietin for symptomatic
      patients with a hemoglobin of 10-11 g/dl and state that erythropoietin should
      strongly be considered if hemoglobin falls to less than 10 g/dl. These
      recommendations were based on studies that revealed an improvement in the quality
      of life of cancer patients, but not patient survival with anemia correction.
      Phase III studies evaluating the correction of anemia via erythropoietin have
      shown mixed results with some studies reporting a decrease in patient survival
      despite an improvement in hemoglobin levels. Diverse functions of erythropoietin
      are reviewed, including its potential to inhibit apoptosis via the JAK2/STAT5/BCL
      X pathway. Correction of anemia by the use of blood transfusions has also shown a
      decrement in patient survival, possibly through inflammatory and/or
      immunosuppressive pathways. CONCLUSIONS: Anemia is a prevalent condition
      associated with cancer and its therapies. Proper Phase III trials are necessary
      to find the best way to correct anemia for specific patients. Future studies of
      erythropoietin must evaluate the possible anti-apoptotic effects by directly
      assessing the tumor for erythropoietin receptors or the presence of the
      JAK2/STAT5/BCL-X pathway. Due to the ability of transfusions to cause
      immunosuppression, most probably through inflammatory pathways, it may be best to
      study the effects of transfusion with the prolonged use of anti-inflammatory
      medications.

PMID- 16111570
TI  - The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence
      based review of the role of radiosurgery for brain metastases.
AB  - PURPOSE: To systematically review the evidence for the use of stereotactic
      radiosurgery in adult patients with brain metastases. METHODS: Key clinical
      questions to be addressed in this evidence-based review were identified. Outcomes
      considered were overall survival, quality of life or symptom control, brain tumor
      control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT
      (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the
      Cochrane library (2004 issue 2) databases were searched using OVID. In addition,
      the Physician Data Query clinical trials database, the proceedings of the
      American Society of Clinical Oncology (ASCO) (1997-2004), ASTRO (1997-2004), and
      the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003)
      were searched. Data from the literature search were reviewed and tabulated. This
      process included an assessment of the level of evidence. RESULTS: For patients
      with newly diagnosed brain metastases, managed with whole-brain radiotherapy
      alone vs. whole-brain radiotherapy and radiosurgery boost, there were three
      randomized controlled trials, zero prospective studies, and seven retrospective
      series (which satisfied inclusion criteria). For patients with up to three (<4
      cm) newly diagnosed brain metastases (and in one study up to four brain
      metastases), radiosurgery boost with whole-brain radiotherapy significantly
      improves local brain control rates as compared with whole-brain radiotherapy
      alone (Level I-III evidence). In one large randomized trial, survival benefit
      with whole-brain radiotherapy was observed in patients with single brain
      metastasis. In this trial, an overall increased ability to taper down on steroid
      dose and an improvement in Karnofsky performance status was seen in patients who
      were treated with radiosurgery boost as compared with patients treated with whole
      brain radiotherapy alone. However, Level I evidence regarding overall quality of
      life outcomes using a validated instrument has not been reported. All randomized
      trials showed improved local control with the addition of radiosurgery to whole
      brain radiotherapy. For patients with multiple brain metastases, there is no
      overall survival benefit with the use of radiosurgery boost to whole-brain
      radiotherapy (Level I-III evidence). Radiosurgery boost is associated with a
      small risk of early or late toxicity. In patients treated with radiosurgery alone
      (withholding whole-brain radiotherapy) as initial treatment, there were 2
      randomized trials, 2 prospective cohort studies, and 16 retrospective series.
      There is Level I to Level III evidence that the use of radiosurgery alone does
      not alter survival as compared to the use of whole-brain radiotherapy. However,
      there is Level I to Level III evidence that omission of whole-brain radiotherapy
      results in poorer intracranial disease control, both local and distant (defined
      as remaining brain, outside the radiosurgery field). Quality of life outcomes
      have not been adequately reported. Radiosurgery is associated with a small risk
      of early or late toxicity. Radiosurgery as salvage for patients with brain
      metastases was reported in zero randomized trials, one prospective study, and
      seven retrospective series. CONCLUSIONS: Based on Level I-III evidence, for
      selected patients with small (up to 4 cm) brain metastases (up to three in number
      and four in one randomized trial), the addition of radiosurgery boost to whole
      brain radiotherapy improves brain control as compared with whole-brain
      radiotherapy alone. In patients with a single brain metastasis, radiosurgery
      boost with whole-brain radiotherapy improves survival. There is a small risk of
      toxicity associated with radiosurgery boost as compared with whole-brain
      radiotherapy alone. In selected patients treated with radiosurgery alone for
      newly diagnosed brain metastases, overall survival is not altered. However, local
      and distant brain control is significantly poorer with omission of upfront whole
      brain radiotherapy (Level I-III evidence). Whether neurocognition or quality of
      life outcomes are different between initial radiosurgery alone vs. whole-brain
      radiotherapy (with or without radiosurgery boost) is unknown, because this has
      not been adequately tested. There was no statistically significant difference in
      overall toxicity between those treated with radiosurgery alone vs. whole-brain
      radiotherapy and radiosurgery boost based on an interim report from one
      randomized study. There is insufficient evidence as to the clinical benefit/risks
      radiosurgery used in the setting of recurrent or progressive brain metastases,
      although radiographic responses are well-documented.

PMID- 16111571
TI  - The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence
      based review of the role of radiosurgery for malignant glioma.
AB  - PURPOSE: To systematically review the evidence for the use of stereotactic
      radiosurgery or stereotactic fractionated radiation therapy in adult patients
      with malignant glioma. METHODS: Key clinical questions to be addressed in this
      evidence-based review were identified. Outcomes considered were overall survival,
      quality of life or symptom control, brain tumor control or response and toxicity.
      MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June
      Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2)
      databases were searched using OVID. In addition, the Physician Data Query
      clinical trials database, the proceedings of the American Society of Clinical
      Oncology (1997-2004), ASTRO (1997-2004), and the European Society of Therapeutic
      Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the
      literature search were reviewed and tabulated. This process included an
      assessment of the level of evidence. RESULTS: For patients with newly diagnosed
      malignant glioma, radiosurgery as boost therapy with conventional external beam
      radiation was examined in one randomized trial, five prospective cohort studies,
      and seven retrospective series. There is Level I evidence that the use of
      radiosurgery boost followed by external beam radiotherapy and carmustine (BCNU)
      does not confer benefit with respect to overall survival, quality of life, or
      patterns of failure as compared with external beam radiotherapy and BCNU. There
      is Level I-III evidence of toxicity associated with radiosurgery boost as
      compared with external beam radiotherapy alone. The results of the prospective
      and retrospective studies may be influenced by selection bias. Radiosurgery used
      as salvage for recurrent or progressive malignant glioma after conventional
      external beam radiotherapy failure was reported in zero randomized trials, three
      prospective cohort studies, and five retrospective series. The available data are
      sparse and insufficient to make absolute recommendations. Stereotactic
      fractionated radiation therapy has been reported as boost therapy with external
      beam radiotherapy for patients with newly diagnosed malignant glioma in only
      three prospective studies. As primary therapy alone without conventional external
      beam radiotherapy for newly diagnosed malignant glioma patients, stereotactic
      fractionated radiation therapy has been reported in only one prospective study.
      There were only three prospective series and two retrospective studies reported
      for patients with recurrent or progressive malignant glioma. CONCLUSIONS: For
      patients with malignant glioma, there is Level I-III evidence that the use of
      radiosurgery boost followed by external beam radiotherapy and BCNU does not
      confer benefit in terms of overall survival, local brain control, or quality of
      life as compared with external beam radiotherapy and BCNU. The use of
      radiosurgery boost is associated with increased toxicity. For patients with
      malignant glioma, there is insufficient evidence regarding the benefits/harms of
      using radiosurgery at the time progression or recurrence. There is also
      insufficient evidence regarding the benefits/harms in the use of stereotactic
      fractionated radiation therapy for patients with newly diagnosed or
      progressive/recurrent malignant glioma.

PMID- 16111572
TI  - MRI changes due to early-delayed conformal radiotherapy and postsurgical effects
      in patients with brain tumors.
AB  - PURPOSE: Discernment of radiotherapy (XRT) effects vs. tumor activity is
      difficult in brain tumor patients during the months after XRT when white matter
      hyperintensities sometimes emerge. We examined brain scans in XRT-treated vs.
      untreated patients for early-delayed post-XRT effects. METHODS AND MATERIALS:
      Brain regions susceptible to XRT injury were examined on magnetic resonance
      imaging (MRI) for T2-weighted hyperintensities and atrophy in 37 adults with low
      grade primary brain tumors (13 nonirradiated and 24 irradiated). Cases evidencing
      recurrence/growth over the study period were censored. Interactions with age,
      mood, fatigue, medications, tumor type and grade, extent of resection, and
      laterality of MRI changes were examined. RESULTS: Hyperintensity and atrophy
      ratings over time for the treated and untreated groups were not significantly
      different. White matter atrophy increased unrelated to XRT. In all patients
      combined, white matter atrophy and hyperintensities were greater at all time
      points and more lateralized in surgically treated patients. CONCLUSIONS:
      Radiotherapy status was not related to changes in MRI ratings during the
      weeks/months after XRT. Findings contradict assumptions about radiographically
      evidenced early-delayed XRT effects. Increases in T2-weighted hyperintensities
      during the 1-6-month period post-conformal radiotherapy for low-grade tumors are
      likely not related to early-delayed XRT effects.

PMID- 16111573
TI  - L-(methyl-11C) methionine positron emission tomography for target delineation in
      resected high-grade gliomas before radiotherapy.
AB  - PURPOSE: Using magnetic resonance imaging (MRI), residual tumor cannot be
      differentiated from nonspecific postoperative changes in operated patients with
      brain gliomas. The higher specificity and sensitivity of L-(methyl-11C)-labeled
      methionine positron emissions tomography (MET-PET) in gliomas has been
      demonstrated in previous studies and is the rationale for the integration of this
      investigation in gross tumor volume delineation. The goal of this trial was to
      quantify the affect of MET-PET vs. with MRI in gross tumor volume definition for
      radiotherapy planning of high-grade gliomas. METHODS AND MATERIALS: The trial
      included 39 patients with resected malignant gliomas. MRI and MET-PET data were
      coregistered based on mutual information. The residual tumor volume on MET-PET
      and the volume of tissue abnormalities on T1-weighted MRI (gadolinium [Gd]
      enhancement) and T2-weighted MRI (hyperintensity areas) were compared using MET
      PET/MRI fusion images. RESULTS: The MET-PET vs. Gd-enhanced T1-weighted MRI
      analysis was performed on 39 patients. In 5 patients (13%), MET uptake
      corresponded exactly with Gd enhancement, and in 29 (74%) of 39 patients, the
      region of MET uptake was larger than that of the Gd enhancement. In 27 (69%) of
      the 39 patients, the Gd enhancement area extended beyond the MET enhancement. MET
      uptake was detected up to 45 mm beyond the Gd enhancement. MET-PET vs. T2
      weighted MRI was investigated in 18 patients. MET uptake did not correspond
      exactly with the hyperintensity areas on T2-weighted MRI in any patient. In 9
      (50%) of 18 patients, MET uptake extended beyond the hyperintensity area on the
      T2-weighted MRI, and in 18 (100%), at least some hyperintensity on the T2
      weighted MRI was located outside the MET enhancement area. MET uptake was
      detected up to 40 mm beyond the hyperintensity area on T2-weighted MRI.
      CONCLUSION: In operated patients with brain gliomas, the size and location of
      residual MET uptake differs considerably from abnormalities found on
      postoperative MRI. Because postoperative changes cannot be differentiated from
      residual tumor by MRI, MET-PET, with a greater specificity for tumor tissue, can
      help to outline the gross tumor volume with greater accuracy.

PMID- 16111574
TI  - Management of acoustic neuromas with fractionated stereotactic radiotherapy
      (FSRT): long-term results in 106 patients treated in a single institution.
AB  - PURPOSE: To assess the long-term outcome and toxicity of fractionated
      stereotactic radiotherapy for acoustic neuromas in 106 patients treated in a
      single institution. PATIENTS AND METHODS: Between October 1989 and January 2004,
      fractionated stereotactic radiotherapy (FSRT) was performed in 106 patients with
      acoustic neuroma (AN). The median total dose applied was 57.6 Gy in median single
      fractions of 1.8 Gy in five fractions per week. The median irradiated tumor
      volume was 3.9 mL (range, 2.7-30.7 mL). The median follow-up time was 48.5 months
      (range, 3-172 months). RESULTS: Fractionated stereotactic radiotherapy was well
      tolerated in all patients. Actuarial local tumor control rates at 3- and 5- years
      after FSRT were 94.3% and 93%, respectively. Actuarial useful hearing
      preservation was 94% at 5 years. The presence of neurofibromatosis (NF-2)
      significantly adversely influenced hearing preservation in patients that
      presented with useful hearing at the initiation of RT (p = 0.00062). Actuarial
      hearing preservation without the diagnosis of NF-2 was 98%. In cases with NF-2,
      the hearing preservation rate was 64%. Cranial nerve toxicity other than hearing
      impairment was rare. The rate of radiation induced toxicity to the trigeminal and
      facial nerve was 3.4% and 2.3%, respectively. CONCLUSION: Fractionated
      stereotactic radiotherapy is safe and efficacious for the treatment of AN, with
      mild toxicity with regard to hearing loss and cranial nerve function. FSRT might
      be considered as an equieffective treatment modality compared to neurosurgery and
      therefore represents an interesting alternative therapy for patients with AN.

PMID- 16111575
TI  - Glycerol rhizotomy versus gamma knife radiosurgery for the treatment of
      trigeminal neuralgia: an analysis of patients treated at one institution.
AB  - BACKGROUND: Medically refractory trigeminal neuralgia (TN) has been treated with
      a variety of minimally invasive techniques, all of which have been compared with
      microvascular decompression. For patients not considered good surgical
      candidates, percutaneous retrogasserian glycerol rhizotomy (GR) and gamma knife
      (GK) radiosurgery are two minimally invasive techniques in common practice
      worldwide and used routinely at Jefferson Hospital for Neuroscience. Using a
      common pain scale outcomes questionnaire, we sought to analyze efficacies and
      morbidities of both treatments. METHODS AND MATERIALS: Between June 1994 and
      December 2002, 79 patients were treated with GR and 109 patients underwent GK for
      the treatment of TN. GR was performed with fluoroscopic guidance as an overnight
      inpatient procedure. GK was performed using a single 4-mm shot positioned at the
      root exit zone of the trigeminal nerve. Radiation doses of 70-90 Gy prescribed to
      the 100% isodose line were used. Treatment outcomes including pain response, pain
      recurrence, treatment failure, treatment-related side effects, and overall
      patient satisfaction with GK and GR were compared using a common outcomes scale.
      Using the Barrow Neurologic Institute pain scale, patients were asked to define
      their level of pain both before and after treatment: I, no pain and no pain
      medication required; I, occasional pain not requiring medication; IIIa, no pain
      and pain medication used; IIIb, some pain adequately controlled with medication;
      IV, some pain not adequately controlled with medication; and V, severe pain with
      no relief with medication. We used posttreatment scores of I, II, IIIa, and IIIb
      to identify treatment success, whereas scores of IV and V were considered
      treatment failure. Results were compiled from respondents and analyzed using SAS
      software. Statistical comparisons used log-rank test, univariate and multivariate
      logistic regression, Fisher's exact test, and Wilcoxon test with significance
      established at p < 0.05. RESULTS: There were 63 evaluable GK patients and 36
      evaluable GR patients. The median follow-up time was 34 and 29 months for the GR
      and GK groups, respectively. The median age was 69 and 70 years and the median
      number of years with TN pain was 6 and 7 years in the GR and GK groups,
      respectively. Thirty-one GR (86%) and 58 GK (92%) patients achieved a successful
      treatment outcome (p = 0.49). The median time to pain relief was < or = 24 h in
      the GR group and 3 weeks in the GK group (p < 0.001, ordinal logistic
      regression). Nineteen GR and 26 GK patients experienced pain recurrence or pain
      never relieved (p = 0.30). The median time to pain recurrence was 5 and 8 months
      in the GR and GK groups, respectively (p = 0.22). At last follow-up, however, a
      statistically significant greater number of GR vs. GK patients had failed
      treatment. Twelve or 33% of GR patients, whereas 8 or 13% of GK patients, had BNI
      scores of 4 or 5 (p = 0.019, Fisher's exact test). When both initial and late
      treatment failures were combined, the overall rate of treatment failures was 39%
      in the GR group and 24% in the GK group (p = 0.023, log-rank). More GR patients
      developed facial numbness and facial numbness morbidity than GK patients: 19 GR
      (54%) and 17 GK patients (30%) developed new facial numbness and 12 GR and 7 GK
      patients reported either somewhat or very bothersome facial numbness (p = 0.018).
      On multivariate analysis, only treatment with GK and severity of pain before
      treatment significantly predicted treatment response. GK patients were more
      likely to have a lower pain score at last follow-up than were GR patients (p =
      0.005, OR = 4.3), and patients with pretreatment pain scores of 5 were more
      likely to have lower posttreatment pain scores than patients with pretreatment
      pain scores of 4 and lower (p = 0.003, OR = 4.0). CONCLUSION: Despite greater
      facial numbness morbidity and a higher failure rate, GR provided more immediate
      pain relief than GK. GR therefore should be considered in patients with disabling
      trigeminal pain requiring urgent pain relief. For all other patients, GK provides
      better long-term pain relief with less treatment-related morbidity, and should
      therefore be considered the preferred treatment for patients with medically
      refractory trigeminal neuralgia who are not suitable candidates for microvascular
      nerve decompression.

PMID- 16111576
TI  - Long-term survival and functional status of patients with low-grade astrocytoma
      of spinal cord.
AB  - PURPOSE: To determine survival and changes in neurologic function and Karnofsky
      performance status (KPS) in a series of patients treated for low-grade
      astrocytoma of the spinal cord during the past two decades. METHODS: This study
      consisted of 14 patients with pathologically confirmed low-grade astrocytoma of
      the spinal cord who were treated between 1980 and 2003. All patients underwent
      decompressive laminectomy followed by biopsy (n = 7), subtotal resection (n = 6),
      or gross total resection (n = 1). Ten patients underwent postoperative
      radiotherapy (median total dose 50 Gy in 28 fractions). The overall survival,
      progression-free survival, and changes in neurologic function and KPS were
      measured. RESULTS: The overall survival rate at 5, 10, and 20 years was 100%,
      75%, and 60%, respectively. The progression-free survival rate at 5, 10, and 20
      years was 93%, 80%, and 60%, respectively. Neither overall survival nor
      progression-free survival was clearly correlated with any patient, tumor, or
      treatment factors. Neurologic function and KPS worsened after surgery in 8 (57%)
      of 14 and 9 (69%) of 13 patients, respectively. At a mean follow-up of 10.2
      years, neurologic function had stabilized or improved in 8 (73%) of 11 remaining
      patients, but the KPS had worsened in 5 (50%) of 10. Most patients who were
      employed before surgery were working at last follow-up. CONCLUSION: Patients who
      undergo gross total resection of their tumor may be followed closely. Patients
      who undergo limited resection should continue to receive postoperative RT (50.4
      Gy in 1.8-Gy fractions). The functional measures should be routinely evaluated to
      appreciate the treatment outcomes.

PMID- 16111577
TI  - Radiation complications and tumor control after 125I plaque brachytherapy for
      ocular melanoma.
AB  - PURPOSE: To determine the outcome of 125I plaque brachytherapy at our institution
      and identify the risk factors associated with the development of radiation
      complications, tumor recurrence, and metastasis. PATIENTS AND METHODS: From 1986
      to 2000, 156 patients underwent 125I episcleral plaque (COMS design) application
      for the treatment of ocular melanoma. Chart analysis of follow-up ophthalmologic
      appointments assessed the incidence of ocular side effects after therapy.
      Statistical analysis assessed outcomes and significant influencing factors.
      RESULTS: With a median follow-up of 6.2 years, the 5-year overall survival was
      83%. The 5-year disease-specific survival was 91%. Initial local control at 5
      years was 92%, with 100% ultimate local control after secondary therapy that
      included 9 enucleations. The risk of metastasis was 10% at 5 years and 27% at 10
      years. Vision stayed the same or improved in 25% of patients, and 44% of patients
      maintained visual acuity better than 20/200. Thirteen percent of patients
      experienced chronic pain or discomfort in the treated eye. Dose rates to the
      tumor apex greater than 90 to 100 cGy/h were associated with increased systemic
      control but worse radiation toxicity. CONCLUSION: Patients in our series
      experienced excellent local tumor control. Higher dose rates to the tumor apex
      were associated with reduced rates of distant metastases but worse ocular
      function.

PMID- 16111578
TI  - Proton beam radiotherapy of iris melanoma.
AB  - PURPOSE: To report on outcomes after proton beam radiotherapy of iris melanoma.
      METHODS AND MATERIALS: Between 1993 and 2004, 88 patients with iris melanoma
      received proton beam radiotherapy, with 53.1 Gy in 4 fractions. RESULTS: The
      patients had a mean age of 52 years and a median follow-up of 2.7 years. The
      tumors had a median diameter of 4.3 mm, involving more than 2 clock hours of iris
      in 32% of patients and more than 2 hours of angle in 27%. The ciliary body was
      involved in 20%. Cataract was present in 13 patients before treatment and
      subsequently developed in another 18. Cataract had a 4-year rate of 63% and by
      Cox analysis was related to age (p = 0.05), initial visual loss (p < 0.0001),
      iris involvement (p < 0.0001), and tumor thickness (p < 0.0001). Glaucoma was
      present before treatment in 13 patients and developed after treatment in another
      3. Three eyes were enucleated, all because of recurrence, which had an actuarial
      4-year rate of 3.3% (95% CI 0-8.0%). CONCLUSIONS: Proton beam radiotherapy of
      iris melanoma is well tolerated, the main problems being radiation-cataract,
      which was treatable, and preexisting glaucoma, which in several patients was
      difficult to control.

PMID- 16111579
TI  - Effectiveness of fractionated stereotactic radiotherapy for uveal melanoma.
AB  - PURPOSE: To study the effectiveness and acute side effects of fractionated
      stereotactic radiation therapy (fSRT) for uveal melanoma. METHODS AND MATERIALS:
      Between 1999 and 2003, 38 patients (21 male, 17 female) were included in a
      prospective, nonrandomized clinical trial (mean follow-up of 25 months). A total
      dose of 50 Gy was given in 5 consecutive days. A blinking light and a camera (to
      monitor the position of the diseased eye) were fixed to a noninvasive relocatable
      stereotactic frame. Primary end points were local control, best corrected visual
      acuity, and toxicity at 3, 6, 12, and 24 months, respectively. RESULTS: After 3
      months (38 patients), the local control was 100%; after 12 months (32 patients)
      and 24 months (15 patients), no recurrences were seen. The best corrected visual
      acuity declined from a mean of 0.21 at diagnosis to 0.06 2 years after therapy.
      The acute side effects after 3 months were as follows: conjunctival symptoms
      (10), loss of lashes or hair (6), visual symptoms (5), fatigue (5), dry eye (1),
      cataract (1), and pain (4). One eye was enucleated at 2 months after fSRT.
      CONCLUSIONS: Preliminary results demonstrate that fSRT is an effective and safe
      treatment modality for uveal melanoma with an excellent local control and mild
      acute side effects. The follow-up should be prolonged to study both long-term
      local control and late toxicity.

PMID- 16111580
TI  - Retrospective analysis of prostate cancer patients with implanted gold markers
      using off-line and adaptive therapy protocols.
AB  - PURPOSE: To determine the efficacy of applying adaptive and off-line setup
      correction models to bony anatomy and gold fiducial markers implanted in the
      prostate, relative to daily alignment to skin tattoos and daily on-line
      corrections of the implanted gold markers. METHODS AND MATERIALS: Ten prostate
      cancer patients with implanted gold fiducial markers were treated using a daily
      on-line setup correction protocol. The patients' positions were aligned to skin
      tattoos and two orthogonal diagnostic digital radiographs were obtained before
      treatment each day. These radiographs were compared with digitally reconstructed
      radiographs to obtain the translational setup errors of the bony anatomy and gold
      markers. The adaptive, no-action-level and shrinking-action-level off-line
      protocols were retrospectively applied to the bony anatomy to determine the
      change in the setup errors of the gold markers. The protocols were also applied
      to the gold markers directly to determine the residual setup errors. RESULTS: The
      percentage of remaining fractions that the gold markers fell within the adaptive
      margins constructed with 1.5sigma' (estimated random variation) after 5, 10, and
      15 measurement fractions was 74%, 88%, and 93% for the prone patients and 55%,
      77%, and 93% for the supine patients, respectively. Using 2sigma', the percentage
      after 5, 10, and 15 measurements was 85%, 95%, and 97% for the prone patients and
      68%, 87%, and 99% for the supine patients, respectively. The average initial
      three-dimensional (3D) setup error of the gold markers was 0.92 cm for the prone
      patients and 0.70 cm for the supine patients. Application of the no-action-level
      protocol to bony anatomy with N(m) = 3 days resulted in significant benefit to 4
      of 10 patients, but 3 were significantly worse. The residual average 3D setup
      error of the gold markers was 1.14 cm and 0.51 cm for the prone and supine
      patients, respectively. When applied directly to the gold markers with N(m) = 3
      days, 5 patients benefited and 3 were significantly worse. The residual 3D error
      of the gold markers was 1.14 cm and 0.76 cm for the prone and supine patients,
      respectively. Application of the shrinking-action-level protocol to bony anatomy
      with an initial action level of 1.0 cm and N(max) = 5 days decreased the residual
      systematic offset of the gold markers in 2 of 10 patients. The residual average
      3D setup error of the gold markers was 1.2 cm and 1.0 cm for the prone and supine
      patients, respectively. When applied directly to the gold markers with N(max) = 5
      days, the residual systematic offset of the gold markers decreased in 6 of 10
      patients (0.84 cm and 0.67 cm for the prone and supine patients, respectively).
      In general, between 3 and 5 of the 10 patients showed significant decreases in
      setup errors with the application of these off-line protocols, and the remaining
      patients showed no significant improvement or showed significantly larger setup
      errors, as determined by the residual error of the gold markers. CONCLUSION:
      Changes in a prostate cancer patient's systematic and random setup
      characteristics during the course of therapy often violate the gaussian
      assumptions of adaptive and off-line correction models. Thus, off-line setup
      correction procedures, especially those directed at prostate localization using
      markers, will result in limited benefit to a minority of patients. The relative
      benefit of on-line localization is still potentially significant if the
      intrafraction motion is relatively small.

PMID- 16111581
TI  - Outcome of salvage radiotherapy for biochemical failure after radical
      prostatectomy with or without hormonal therapy.
AB  - BACKGROUND: This study analyzed the outcome of salvage radiotherapy for
      biochemical failure after radical prostatectomy (RP). By comparing the outcomes
      for patients who received RT alone and for those who received combined RT and
      hormonal therapy, we assessed the potential benefits of hormonal therapy.
      PATIENTS AND METHODS: This cohort was comprised of 101 patients who received
      salvage RT between 1990 and 2001 for biochemical failure after RP. Fifty-nine of
      these patients also received hormone. Margin status (positive vs. negative),
      extracapsular extension (yes vs. no), seminal vesicle involvement (yes vs. no),
      pathologic stage, Gleason score, pre-RP PSA, post-RP PSA, pre-RT PSA, hormonal
      use, radiotherapy dose and technique, RP at M. D. Anderson Cancer Center, and
      time from RP to salvage RT were analyzed. Statistically significant variables
      were used to construct prognostic groups. RESULTS: Independent prognostic factors
      for the RT-alone group were margin status and pre-RT PSA. RP at M. D. Anderson
      Cancer Center was marginally significant (p = 0.06) in multivariate analysis. Pre
      RT PSA was the only significant prognostic factor for the combined-therapy group.
      We used a combination of margin status and pre-RT PSA to construct a prognostic
      model for response to the salvage treatment based on the RT group. We identified
      the favorable group as those patients with positive margin and pre-RT PSA < or =
      0.5 ng/mL vs. the unfavorable group as otherwise. This stratification separates
      patients into clinically meaningful groups. The 5-year PSA control probabilities
      for the favorable vs. the unfavorable group were 83.7% vs. 61.7% with
      radiotherapy alone (p = 0.03). Androgen ablation seemed to be most beneficial in
      the unfavorable group. CONCLUSION: After prostatectomy, favorable-group patients
      may fare well with salvage radiotherapy alone. These patients may be spared the
      toxicity of androgen ablation. The other patients may benefit most from a
      combined approach with hormonal treatment. We further suggest that salvage
      radiotherapy should be given early when the PSA is still low.

PMID- 16111582
TI  - Phase II dose escalation study of image-guided adaptive radiotherapy for prostate
      cancer: use of dose-volume constraints to achieve rectal isotoxicity.
AB  - PURPOSE: In our Phase II prostate cancer Adaptive Radiation Therapy (ART) study,
      the highest possible dose was selected on the basis of normal tissue tolerance
      constraints. We analyzed rectal toxicity rates in different dose levels and
      treatment groups to determine whether equivalent toxicity rates were achieved as
      hypothesized when the protocol was started. METHODS AND MATERIALS: From 1999 to
      2002, 331 patients with clinical stage T1 to T3, node-negative prostate cancer
      were prospectively treated with three-dimensional conformal adaptive RT. A
      patient-specific confidence-limited planning target volume was constructed on the
      basis of 5 CT scans and 4 sets of electronic portal images after the first 4 days
      of treatment. For each case, the rectum (rectal solid) was contoured in its
      entirety. The rectal wall was defined by use of a 3-mm wall thickness (median
      volume: 29.8 cc). The prescribed dose level was chosen using the following rectal
      wall dose constraints: (1) Less than 30% of the rectal wall volume can receive
      more than 75.6 Gy. (2) Less than 5% of the rectal wall can receive more than 82
      Gy. Low-risk patients (PSA < 10, Stage < or = T2a, Gleason score < 7) were
      treated to the prostate alone (Group 1). All other patients, intermediate and
      high risk, where treated to the prostate and seminal vesicles (Group 2). The risk
      of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the
      different dose levels prescribed. HIC approval was acquired for all patients.
      Median follow-up was 1.6 years. RESULTS: Grade 2 chronic rectal toxicity was
      experienced by 34 patients (10%) (9% experienced rectal bleeding, 6% experienced
      proctitis, 3% experienced diarrhea, and 1% experienced rectal pain) at a median
      interval of 1.1 year. Nine patients (3%) experienced grade 3 or higher chronic
      rectal toxicity (1 Grade 4) at a median interval of 1.2 years. The 2-year rates
      of Grade 2 or higher and Grade 3 or higher chronic rectal toxicity were 17% and
      3%, respectively. No significant difference by dose level was seen in the 2-year
      rate of Grade 2 or higher chronic rectal toxicity. These rates were 27%, 15%,
      14%, 17%, and 24% for dose levels equal to or less than 72, 73.8, 75.6, 77.4, and
      79.2 Gy, respectively (p = 0.3). Grade 2 or higher chronic rectal bleeding was
      significantly greater for Group 2 than for Group 1, 17% vs. 8% (p = 0.035).
      CONCLUSIONS: High doses (79.2 Gy) were safely delivered in selected patients by
      our adaptive radiotherapy process. Under the rectal dose-volume histogram
      constraints for the dose level selection, the risk of chronic rectal toxicity is
      similar among patients treated to different dose levels. Therefore, rectal
      chronic toxicity rates reflect the dose-volume cutoff used and are independent of
      the actual dose levels. On the other hand, a larger PTV will increase the rectal
      wall dose and chronic rectal toxicity rates. PTV volume and dose constraints
      should be defined, considering their potential benefit.

PMID- 16111583
TI  - Rectal fistulas after prostate brachytherapy.
AB  - PURPOSE: To compare the rectal and prostatic radiation doses for a prospective
      series of 503 patients, 44 of whom developed persistent rectal bleeding, and 2 of
      whom developed rectal-prostatic fistulas. METHODS AND MATERIALS: The 503 patients
      were randomized and treated by implantation with 125I vs. 103Pd alone (n = 290)
      or to 103Pd with 20 Gy vs. 44 Gy supplemental external beam radiotherapy (n =
      213) and treated at the Puget Sound Veterans Affairs Medical Center (n = 227),
      Schiffler Cancer Center (n = 242) or University of Washington (n = 34). Patients
      were treated between September 1998 and October 2001 and had a minimum of 24
      months of follow-up. The patient groups were treated concurrently. Treatment
      related morbidity was monitored by mailed questionnaires, using standard American
      Urological Association and Radiation Therapy Oncology Group criteria, at 1, 3, 6,
      12, 18, and 24 months. Patients who reported Grade 1 or greater Radiation Therapy
      Oncology Group rectal morbidity were interviewed by telephone to clarify details
      regarding their rectal bleeding. Those who reported persistent bleeding, lasting
      for >1 month were included as having Grade 2 toxicity. Three of the patients with
      rectal bleeding required a colostomy, two of whom developed a fistula. No patient
      was lost to follow-up. The rectal doses were defined as the rectal volume in
      cubic centimeters that received >50%, 100%, 200%, or 300% of the prescription
      dose. The rectum was considered as a solid structure defined by the outer wall,
      without attempting to differentiate the inner wall or contents. RESULTS:
      Persistent rectal bleeding occurred in 44 of the 502 patients, 32 of whom (73%)
      underwent confirmatory endoscopy. In univariate analysis, multiple parameters
      were associated with late rectal bleeding, including all rectal brachytherapy
      indexes. In multivariate analysis, however, only the rectal volume that received
      >100% of the dose was significantly predictive of bleeding. Rectal fistulas
      occurred in 2 patients (0.4%), both of whom had received moderate rectal
      radiation doses and extensive intervention for rectal bleeding. CONCLUSION:
      Partly on the basis of data from others and data presented here, we believe that
      the incidence of rectal fistulas can be much lower than in our series. High
      rectal radiation doses should be avoided a priori, to minimize the likelihood of
      rectal bleeding, and hence the likelihood that invasive procedures will be
      performed.

PMID- 16111584
TI  - Predictive factors for erectile dysfunction in men with prostate cancer after
      brachytherapy: is dose to the penile bulb important?
AB  - PURPOSE: To determine predictive factors for postimplant erectile dysfunction
      (ED) in a cohort of patients, according to prospectively collected data;
      specifically, to assess the impact of penile bulb volume and D50 and D95 (dose
      covering 50% and 95% of the penile bulb volume, respectively) on ED. METHODS AND
      MATERIALS: Three hundred forty-two patients were identified who were potent
      before implant and who had at least 2 years' follow-up. Patient, tumor,
      treatment, and dosimetric data were collected on all patients. Postimplant ED was
      defined according to both physician-documented and patient-documented outcome
      data. Binary logistic regression analysis was used to create multivariable models
      of predictors for ED at 1, 2, and 3 years after implant. RESULTS: Physician
      documented rates of ED were 57%, 48%, and 38% at 1, 2, and 3 years after implant,
      respectively. Patient-documented rates of ED were 70% and 66% at 1 and 2 years,
      respectively. Multivariable analyses revealed age and degree of pre-implant
      erectile function to be consistently significant predictors of ED. Use of
      hormones was significant at the 1-year physician-documented ED endpoint but not
      thereafter, in keeping with the time course of testosterone recovery. Penile bulb
      volume, D50, and D95 were not found to be predictive for ED at any time point, in
      contrast to previous studies. In addition, planning ultrasound target volume,
      number of needles, and institutional case sequence number were significant
      predictors of ED at various time points, consistent with a traumatic etiology of
      ED. CONCLUSIONS: We found no evidence to support penile bulb dosimetry as an
      independent predictive factor for ED after implant, using physician-documented or
      patient-documented outcomes.

PMID- 16111585
TI  - The effect of tumor location and respiratory function on tumor movement estimated
      by real-time tracking radiotherapy (RTRT) system.
AB  - PURPOSE: The effects of tumor location and pulmonary function on the motion of
      fiducial markers near lung tumors were evaluated to deduce simple guidelines for
      determining the internal margin in radiotherapy without fiducial markers. METHODS
      AND MATERIALS: Pooled data collected by a real-time tumor-tracking radiotherapy
      system on 42 markers in 39 patients were analyzed. The pulmonary functions of all
      patients were assessed before radiotherapy. Using chest X-ray film, the position
      of the marker was expressed relative to the geometry of the unilateral lung.
      Posterior location meant the area of the posterior half of the lung in a lateral
      chest X-ray film, and caudal location meant the caudal half of the chest X-ray
      film; these categories were determined by measuring the distance between the
      marker and anatomic landmarks, including the apex, costophrenic angle, midline of
      spinal canal, lateral, anterior, and posterior boundary of the lung. RESULTS:
      Before the radiotherapy, 18 patients had obstructive respiratory dysfunction
      (ratio of forced expiratory volume in 1 s to forced vital capacity [FEV1.0/FVC]
      <70), 5 patients had constrictive dysfunction (percent vital capacity [%VC] <80),
      and 3 had mixed dysfunction. Means of FEV1.0/FVC and %VC were 97.0% and 66.5%,
      respectively. Median tumor movements in the x (left-right), y (anteroposterior),
      and z (craniocaudal) directions were 1.1 mm, 2.3 mm, and 5.4 mm, respectively.
      There was no significant correlation between respiratory function and magnitude
      of marker movement in any direction. Median marker movement in the z direction
      was 2.6 mm for the cranial location and 11.8 mm for the caudal location,
      respectively (p < 0.001). Median movement in the z direction was 11.8 mm for
      posterior location and 3.4 mm for anterior location, respectively (p < 0.01).
      CONCLUSIONS: Simple measurement of the relative location on plain chest X-ray
      film was related, but respiratory function test was not related, to the
      craniocaudal amplitude of the motion of the fiducial marker near lung tumors.

PMID- 16111586
TI  - CT-based definition of thoracic lymph node stations: an atlas from the University
      of Michigan.
AB  - PURPOSE: Accurate delineation of the mediastinal and hilar lymph node regions is
      essential for a reproducible definition of target volumes used in conformal
      irradiation of non-small-cell lung cancer. The goal of this work was to generate
      a consensus to delineate these nodal regions based on definitions from the
      American Joint Committee on Cancer. METHODS AND MATERIALS: A dedicated thoracic
      radiologist, thoracic surgeon, medical physicist, and three radiation oncologists
      were gathered to generate a three-dimensional radiologic description for the
      mediastinal and hilar nodal regions on axial CT scans. This paper proposes an
      atlas of most of the lymph node stations described by Mountain and Dresler.
      RESULTS: The CT boundaries of lymph node stations 1-2, 3, 4, 5, 6, 7, 8, 10-11
      were defined on axial CT, along with image illustrations. CONCLUSION: These CT
      based illustrative definitions will provide guidelines for clinical practice and
      studies evaluating incidental radiation in radiotherapy. Studies are ongoing at
      the University of Michigan to measure quantitatively the incidental nodal
      radiation received by patients with non-small-cell lung cancer.

PMID- 16111587
TI  - Esophagus sparing with IMRT in lung tumor irradiation: an EUD-based optimization
      technique.
AB  - PURPOSE: The aim of this study was to evaluate (1) the use of generalized
      equivalent uniform dose (gEUD) to optimize dose escalation of lung tumors when
      the esophagus overlaps the planning target volume (PTV) and (2) the potential
      benefit of further dose escalation in only the part of the PTV that does not
      overlap the esophagus. METHODS AND MATERIALS: The treatment-planning computed
      tomography (CT) scans of patients with primary lung tumors located in different
      regions of the left and right lung were used for the optimization of beamlet
      intensity modulated radiation therapy (IMRT) plans. In all cases, the PTV
      overlapped part of the esophagus. The dose in the PTV was maximized according to
      7 different primary cost functions: 2 plans that made use of mean dose (MD) (the
      reference plan, in which the 95% isodose surface covered the PTV and a second
      plan that had no constraint on the minimum isodose), 3 plans based on maximizing
      gEUD for the whole PTV with ever increasing assumptions for tumor aggressiveness,
      and 2 plans that used different gEUD values in 2 simultaneous, overlapping target
      volumes (the whole PTV and the PTV minus esophagus). Beam arrangements and NTCP
      based costlets for the organs at risk (OARs) were kept identical to the original
      conformal plan for each case. Regardless of optimization method, the relative
      ranking of the resulting plans was evaluated in terms of the absence of cold
      spots within the PTV and the final gEUD computed for the whole PTV. RESULTS:
      Because the MD-optimized plans lacked a constraint on minimum PTV coverage, they
      resulted in cold spots that affected approximately 5% of the PTV volume. When
      optimizing over the whole PTV volume, gEUD-optimized plans resulted in higher
      equivalent uniform PTV doses than did the reference plan while still maintaining
      normal-tissue constraints. However, only under the assumption of extremely
      aggressive tumors could cold spots in the PTV be avoided. Generally, high-level
      overall results are obtained when optimization in the whole PTV is also
      associated with a second simultaneous optimization in the PTV minus overlapping
      portions of the esophagus. CONCLUSIONS: Intensity modulated radiation therapy
      optimizations that utilize gEUD-based cost functions for the PTV and NTCP-based
      constraints for the OARs result in increased doses to large portions of the PTV
      in cases where the PTV overlaps the esophagus, while still maintaining (and
      confining to the overlap region) minimum dose coverage equivalent to the
      homogeneous PTV optimization cases.

PMID- 16111588
TI  - A prospective randomized study to compare the molecular response rates between
      central lymphatic irradiation and intensive alternating triple chemotherapy in
      the treatment of stage I-III follicular lymphoma.
AB  - PURPOSE: This study was undertaken to compare the molecular response (MR) rates
      of 2 regimens, central lymphatic irradiation (CLI) and alternating triple therapy
      (ATT), in the treatment of Stage I-III follicular lymphoma. MR was defined as
      disappearance of t(14;18) (q32;q21) amplified by polymerase chain reaction (PCR).
      PATIENTS AND METHODS: Sixty-five patients with Stage I to III follicular lymphoma
      were randomized. CLI consisted of the mantle, abdomen, and pelvic radiation
      fields. ATT alternated among CHOD-Bleo, ESHAP, and NOPP for 12 courses. Bone
      marrow (BM) and peripheral blood (PB) samples were obtained before treatment for
      PCR analysis. PCR-positive patients were followed by PCR analysis. The random
      effects logistic model was fitted to the data from the posttreatment PCRs. The
      factors included in the model were treatment arm, type of PCR (BM vs. PB), and
      time to PCR sample procurement from the date of registration. RESULTS: At a
      median follow-up of 71 months, the 5-year relapse-free survival (RFS) rates were
      45% and 54% for CLI and ATT, respectively (p = 0.42). The probability of
      attaining an MR increased with time after registration (p = 0.007), was lower for
      BM compared with PB (p = 0.012), and was higher for ATT than for CLI (p = 0.020).
      CONCLUSION: ATT regimen achieved a higher MR than CLI, although both arms had
      similar 5-year RFS.

PMID- 16111589
TI  - Gamma camera scans and pretreatment tumor volumes as predictors of response and
      progression after Y-90 anti-CD20 radioimmunotherapy.
AB  - PURPOSE: To evaluate two potential approaches to predicting site-specific
      patterns of recurrence after yttrium-90 ibritumomab tiuxetan radioimmunotherapy
      (RIT) for CD20+ B-cell Non-Hodgkin's lymphoma. These predictive methods may be
      useful in evaluating the utility of local intensification of individual nodal or
      extranodal sites using external beam radiotherapy. METHODS AND MATERIALS: Records
      and images were evaluated for 20 patients previously treated with yttrium-90
      ibritumomab RIT. Intensity of isotope uptake on the pretreatment two-dimensional
      antibody scans and maximal extent of tumor deposits found on computed tomography
      images of each anatomic site were correlated with response and subsequent
      patterns of recurrence or progression. RESULTS: Our data failed to suggest a
      significant correlation between the site-by-site two-dimensional image intensity
      on the pre-RIT scan and the likelihood of response at those sites. In contrast,
      an analysis of pretreatment target volumes did correlate significantly with
      progression. A collective analysis of disease sites from all 20 patients found
      that 83% (10/12) sites of "bulky" (maximal diameter > or = 5 cm) disease
      displayed evidence of progression vs. 28% (26/93) of "nonbulky" disease sites
      containing gross disease but no area measuring >5 cm (p < 0.001). All patients
      with at least one site of bulky disease had initial disease progression occur at
      a bulky site, with a bulky site being the sole first site of progression in
      approximately 50%. In patients with only nonbulky disease sites, approximately
      one third progressed initially at an entirely new site of disease. CONCLUSION: We
      conclude that we can use tumor bulk to establish a statistical hierarchy of
      likely tumor progression sites and use this pattern to direct the use of
      additional external beam radiotherapy to augment treatment.

PMID- 16111590
TI  - Influence of site on the therapeutic ratio of adjuvant radiotherapy in soft
      tissue sarcoma of the extremity.
AB  - PURPOSE: The ultimate goal of adjuvant radiotherapy (RT) in soft-tissue sarcoma
      of the extremity is to improve the therapeutic ratio by increasing local control
      while minimizing morbidity. Most efforts in trying to improve this ratio have
      focused on the sequencing of RT and surgery, with little attention to the
      potential influence of the tumor site. The purpose of this study was to determine
      the influence of tumor site on local control and complications in a group of
      patients with primary high-grade soft-tissue sarcoma of the extremity treated at
      a single institution with postoperative RT. METHODS AND MATERIALS: Between July
      1982 and December 2000, 369 adult patients with primary high-grade soft-tissue
      sarcoma of the extremity were treated with limb-sparing surgery and postoperative
      RT. Patients who underwent surgery or RT outside our institution were excluded.
      The tumor site was the upper extremity (UE) in 103 (28%) and the lower extremity
      (LE) in 266 (72%). The tumor was < or = 5 cm in 98 patients (27%), and the
      microscopic margins were positive in 44 (12%). Of the 369 patients, 104 (28%)
      underwent postoperative external beam RT (EBRT), 233 (63%) postoperative
      brachytherapy (BRT), and 32 underwent a combination (9%); 325 (88%) received a
      "conventional" radiation dose, defined as 60-70 Gy for EBRT, 45 Gy for BRT, and
      45-50 Gy plus 15-20 Gy for EBRT plus BRT. Complications were assessed in terms of
      wound complications requiring repeat surgery, fracture, joint stiffness, edema,
      and Grade 3 or worse peripheral nerve damage. RESULTS: The UE and LE groups were
      balanced with regard to age, depth, margin status, and type of RT (EBRT vs. BRT
      +/- EBRT). However, more patients in the UE group had tumors < or = 5 cm and more
      received a conventional radiation dose (p = 0.01 and P = 0.03, respectively).
      With a median follow-up of 50 months, the 5-year actuarial rate of local control,
      distant relapse-free survival, and overall survival for the whole population was
      82% (95% confidence interval [CI], 77-86%), 61% (95% CI, 56-66%), and 71% (95%
      CI, 66-76%), respectively. The 5-year local control rate in patients with UE STS
      was 70% (95% CI, 60-80%) compared with 86% (95% CI, 81-91%) for LE STS (p =
      0.0004). On multivariate analysis, an UE site (p = 0.001; relative risk [RR], 3;
      95% CI, 2-5) and positive resection margins (p = 0.02; RR, 2; 95% CI, 1-4) were
      significant predictors of poor local control. The RT type or radiation dose, age,
      tumor depth, and size were not significant predictors of local control. The 5
      year wound reoperation rate was 1% (95% CI, 0-3) in the UE compared with 11% (95%
      CI, 7-15) in the LE (p = 0.002). On multivariate analysis, the UE site retained
      its significance as a predictor of low wound complications (p = 0.001; RR, 0.08;
      95% CI, 0.01-0.7). The site did not significantly influence the incidence of
      fracture (p = 0.7), joint stiffness (p = 0.2), edema (p = 0.5), or Grade 3 or
      worse peripheral nerve damage (p = 0.3). CONCLUSION: The UE site is associated
      with a greater rate of local recurrence compared with the LE. This difference was
      independent of other variables and could not be accounted for by an imbalance
      between the two groups. With a lower wound complication rate associated with an
      UE site, it would be of interest to determine whether preoperative RT and/or
      intensity-modulated RT can increase the local control in UE sarcomas, thus
      improving the therapeutic ratio.

PMID- 16111591
TI  - Definition of postlumpectomy tumor bed for radiotherapy boost field planning: CT
      versus surgical clips.
AB  - PURPOSE: To compare the location and extent of the tumor bed as defined by
      surgical clips and computed tomography (CT) scans, after lumpectomy, for electron
      boost planning as part of breast radiotherapy. METHODS AND MATERIALS: Planning CT
      images of 31 operated breasts in 30 patients who underwent lumpectomy were
      reviewed. One or more clips were placed in the lumpectomy cavity. Serial CT
      images were used to measure the depth and transverse and longitudinal dimensions.
      The area and geometric center of the tumor bed were defined by the clips and CT.
      RESULTS: The CT and clip measurements were identical for the maximal tumor depth
      in 27 of 30 patients. The CT bed extended beyond the clips by 0-7 mm medially in
      the transverse/longitudinal extent (multiclip patients). The median distance
      between the geometric centers in the coronal plane for the tumor bed center was
      larger for patients with single clips than for those with multiple clips (p <
      0.025). Tumor bed areas in the coronal plane defined by both methods correlated
      strongly. However, the CT-defined area was larger by 13.9 mm2. The CT bed was
      more readily visible in patients with a shorter interval between surgery and
      radiotherapy. CONCLUSION: The maximal depth of the tumor bed was similar using
      the two methods. The extent and centers of the clip-and CT-determined beds
      differed significantly. This may indicate an underestimation of the tumor bed as
      defined by clips only and justifies integration of CT information in boost field
      planning.

PMID- 16111592
TI  - The incidence and functional consequences of RT-associated cardiac perfusion
      defects.
AB  - PURPOSE: Radiation therapy (RT) for left-sided breast cancer has been associated
      with cardiac dysfunction. We herein assess the temporal nature and volume
      dependence of RT-induced left ventricular perfusion defects and whether these
      perfusion defects are related to changes in cardiac wall motion or alterations in
      ejection fraction. METHODS: From 1998 to 2001, 114 patients were enrolled onto an
      IRB-approved prospective clinical study to assess changes in regional and global
      cardiac function after RT for left-sided breast cancer. Patients were imaged 30
      to 60 minutes after injection of technetium 99m sestamibi or tetrofosmin. Post-RT
      perfusion scans were compared with the pre-RT studies to assess for RT-induced
      perfusion defects as well as functional changes in wall motion and ejection
      fraction. Two-tailed Fisher's exact test and the Cochran-Armitage test for linear
      trends were used for statistical analysis. RESULTS: The incidence of new
      perfusion defects 6, 12, 18, and 24 months after RT was 27%, 29%, 38%, and 42%,
      respectively. New defects occurred in approximately 10% to 20% and 50% to 60% of
      patients with less than 5%, and greater than 5%, of their left ventricle included
      within the RT fields, respectively (p = 0.33 to 0.00008). The rates of wall
      motion abnormalities in patients with and without perfusion defects were 12% to
      40% versus 0% to 9%, respectively; p values were 0.007 to 0.16, depending on the
      post-RT interval. CONCLUSIONS: Radiation therapy causes volume-dependent
      perfusion defects in approximately 40% of patients within 2 years of RT. These
      perfusion defects are associated with corresponding wall-motion abnormalities.
      Additional study is necessary to better define the long-term functional
      consequences of RT-induced perfusion defects.

PMID- 16111593
TI  - Relative biologic effectiveness in terms of tumor response of 125I implants
      compared with 60Co gamma rays.
AB  - PURPOSE: To measure the relative biologic effectiveness (RBE) for 125I seeds
      compared with external beam radiotherapy using a clinically relevant in vivo
      system. METHODS AND MATERIALS: Photon emission from a detailed source model was
      simulated using the Monte Carlo code MCNP4C, sampling from a 125I spectrum. The
      mouse RIF-1 tumor was treated with either temporary implant of an 125I seed or
      with 60Co gamma rays. The tumors were always the same size at the initiation of
      treatment, and the endpoint was growth inhibition. RESULTS: The dose-response
      curve for both modalities was close to linear and was independent of the initial
      125I activity (dose rate) for the range investigated. Calculation of the RBE for
      tumor response requires assigning a unique value for the tumor dose that is not
      homogenous but depends on the distance from the 125I source. Because tumor
      regrowth will depend on the subpopulation of cells that have the greatest
      probability of survival (i.e., those at the greatest distance from the 125I
      source), one approach is to use the dose to this population. On this basis, the
      RBE for 125I compared with 60Co gamma rays is 1.5. If the 125I dose is computed
      as the average dose to the tumor, corrected for the dose that is wasted as
      overkill in the cell population closest to the center of the 125I seed, the RBE
      is 1.4. CONCLUSION: The result, an RBE of 1.4-1.5 is similar to findings obtained
      by other methods, supporting the validity of this approach to derive an RBE with
      validity in a clinical context.

PMID- 16111594
TI  - Combined effects of radiation and interleukin-13 receptor-targeted cytotoxin on
      glioblastoma cell lines.
AB  - PURPOSE: Interleukin-13 receptor-targeted cytotoxin (IL13-PE38) is highly
      cytotoxic to human glioblastoma (GBM) cells. Although this molecule is being
      tested in a multicenter Phase III clinical trial (PRECISE Study) in patients with
      recurrent disease, the activity of IL13-PE38 when combined with radiation therapy
      has not been investigated. METHODS AND MATERIALS: Cytotoxicity of IL13-PE38 to
      GBM cell lines was assessed by protein synthesis inhibition and clonogenic
      assays, and the growth of GBM cells receiving radiation was assessed by thymidine
      uptake assays. Expression of IL-13 receptor alpha2 (IL-13Ralpha2) messenger
      ribonucleic acid (mRNA) in GBM cells exposed to radiation was assessed by
      quantitative reverse transcriptase/polymerase chain reaction (RT-PCR) and IL-13R
      density by radiolabeled IL-13 binding assays. RESULTS: Prior irradiation of GBM
      cell lines followed by IL13-PE38 treatment did not enhance cytotoxicity; however,
      concomitant 5 Gy irradiation and IL13-PE38 treatment was highly cytotoxic to
      T98G, M059K, A172, and LN-229 cell lines as determined by cell viability assays.
      There was a statistically significant decrease in number of viable cells in IL13
      PE38 and irradiated cells compared with irradiated cells alone (p < 0.05) or IL13
      PE38 treated cells alone (p < 0.05). In contrast, U251, SN19, and U87MG cell
      lines did not show any combined effect. These results were confirmed by
      clonogenic assays. Although three GBM cell lines-U251, SN19, and A172-showed 2.8-
      to 13.9-fold upregulation of IL-13Ralpha2 mRNA expression at 6-24 h after
      exposure to 5 Gy radiation, specific binding of radiolabeled IL-13 to these cell
      lines did not improve. CONCLUSIONS: Our results suggest that concomitant
      radiation therapy and IL13-PE38 treatment may be beneficial for the treatment of
      patients with GBM. This strategy may be worth exploring in animal models of human
      glioma.

PMID- 16111595
TI  - Toxicity, biodistribution, and convection-enhanced delivery of the boronated
      porphyrin BOPP in the 9L intracerebral rat glioma model.
AB  - PURPOSE: To investigate the toxicity, biodistribution, and convection-enhanced
      delivery (CED) of a boronated porphyrin (BOPP) that was designed for boron
      neutron capture therapy and photodynamic therapy. METHODS AND MATERIALS: For the
      toxicity study, Fischer 344 rats were injected with graded concentrations of BOPP
      (35-100 mg/kg) into the tail vein. For boron biodistribution studies, 9L tumor
      bearing rats received BOPP either systematically (intravenously) or locally.
      RESULTS: All rats that received 70 mg/kg BOPP and 70% of rats that received < or
      = 60 mg/kg BOPP i.v. either had to be euthanized or died within 4 days of
      injection. In the biodistribution study, boron levels were relatively high in
      liver, kidney, spleen, and adrenal gland tissue, and moderate levels were found
      in all other organs. The maximum tumor boron concentration was 21.4 mug/g at 48 h
      after i.v. injection; this concentration of boron in brain tumors is at the low
      end of the range considered optimal for therapy. In addition, the tumor/blood
      ratio (approximately 1.2) was not optimal. When BOPP was delivered directly into
      intracerebral 9L tumors with CED, we obtained tumor boron concentrations much
      greater than those obtained by i.v. injection. Convection-enhanced delivery of
      1.5 mg BOPP produced an average tumor boron level of 519 mug/g and a tumor/blood
      ratio of approximately 1850:1. CONCLUSIONS: Our study demonstrates that changing
      the method of BOPP delivery from i.v. to CED significantly enhances the boron
      concentration in tumors and produces very favorable tumor/brain and tumor/blood
      ratios.

PMID- 16111596
TI  - Use of maximum intensity projections (MIP) for target volume generation in 4DCT
      scans for lung cancer.
AB  - PURPOSE: Single four-dimensional CT (4DCT) scans reliably capture intrafractional
      tumor mobility for radiotherapy planning, but generating internal target volumes
      (ITVs) requires the contouring of gross tumor volumes (GTVs) in up to 10 phases
      of a 4DCT scan, as is routinely performed in our department. We investigated the
      use of maximum intensity projection (MIP) protocols for rapid generation of ITVs.
      METHODS AND MATERIALS: 4DCT data from a mobile phantom and from 12 patients with
      Stage I lung cancer were analyzed. A single clinician contoured GTVs in all
      respiratory phases of a 4DCT, as well as in three consecutive phases selected for
      respiratory gating. MIP images were generated from both phantom and patient data,
      and ITVs were derived from encompassing volumes of the respective GTVs. RESULTS:
      In the phantom study, the ratio between ITVs generated from all 10 phases and
      those from MIP scans was 1.04. The corresponding center of mass of both ITVs
      differed by less than 1 mm. In scans from patients, good agreement was observed
      between ITVs derived from 10 and 3 (gating) phases and corresponding MIPs, with
      ratios of 1.07 +/- 0.05 and 0.98 +/- 0.05, respectively. In addition, the center
      of mass of the respective ITVs differed by only 0.4 and 0.5 mm. CONCLUSION: MIPs
      are a reliable clinical tool for generating ITVs from 4DCT data sets, thereby
      permitting rapid assessment of mobility for both gated and nongated 4D
      radiotherapy in lung cancer.

PMID- 16111597
TI  - Organ sparing by conformal avoidance intensity-modulated radiation therapy for
      anal cancer: dosimetric evaluation of coverage of pelvis and inguinal/femoral
      nodes.
AB  - PURPOSE: To describe a novel and straightforward conformal avoidance intensity
      modulated radiation therapy (IMRT) technique for coverage of pelvis and
      inguinal/femoral nodes and to compare the dosimetry of the new method with that
      of other traditional methods of radiation treatment. METHODS AND MATERIALS: Data
      of 2 patients with anal cancer were used as example cases to illustrate details
      and advantages of conformal avoidance IMRT technique. Conventional photons with
      enface electrons design was created first, thereby providing "outermost
      boundaries" defined as planning target volume (PTV) for subsequent conformal
      avoidance IMRT design. Organs at risk (OARs), including femoral head and neck and
      external genitalia, were contoured as conformal avoidance structures. A step-and
      shoot inverse IMRT planning was subsequently generated. For dosimetric
      comparison, a recently published technique by modified segmental boost was also
      generated. These treatment techniques were evaluated by dose-volume histogram
      (DVH) of PTV and OARs. Dose profiles at four different depths from each treatment
      planning were generated for comparison. RESULTS: The DVH of PTV showed that
      coverage of the PTV was comparable among three treatment techniques. Percent
      volume of PTV receiving more than 90% prescription dose was in the range 94-98%
      for the three treatment techniques, and all had only 0-2% of PTV receiving more
      than 110% of prescription dose. The DVH of OARs confirmed that both femoral head
      and neck and external genitalia could be spared well by conformal avoidance IMRT
      as compared with the other two techniques. Although greater inhomogeneity of dose
      distribution within the PTV was noted by conformal avoidance IMRT technique, as
      shown by dose profiles at four different depths, the maximum doses at different
      depths were less than 115%, which was comparable to those planned by modified
      segmental boost technique. Planning by photons and enface electrons technique,
      however, showed a greater dose variation up to 134% of the prescription dose at
      1.5 cm depth along photon-electron match-line. CONCLUSIONS: To cover pelvis and
      inguinal/femoral nodes, conformal avoidance IMRT is technically simple to
      simulate, plan, and execute. Dosimetric study has demonstrated that it achieves
      comparable PTV coverage compared with other approaches while at the same time
      significantly sparing the surrounding OARs.

PMID- 16111598
TI  - Influence of radiotherapy on the latest generation of implantable cardioverter
      defibrillators.
AB  - PURPOSE: Radiotherapy can influence the functioning of pacemakers and implantable
      cardioverter-defibrillators (ICDs). ICDs offer the same functionality as
      pacemakers, but are also able to deliver a high-voltage shock to the heart if
      needed. Guidelines for radiotherapy treatment of patients with an implanted
      rhythm device have been published in 1994 by The American Association of
      Physicists in Medicine, and are based only on experience with pacemakers. Data on
      the influence of radiotherapy on ICDs are limited. The objective of our study is
      to determine the influence of radiotherapy on the latest generation of ICDs.
      METHODS AND MATERIALS: Eleven modern ICDs have been irradiated in our department.
      The irradiation was performed with a 6-MV photon beam. The given dose was
      fractionated up to a cumulative dose of 120 Gy. Two to 5 days passed between
      consecutive irradiations. Frequency, output, sensing, telemetry, and shock energy
      were monitored. RESULTS: Sensing interference by ionizing radiation on all ICDs
      has been demonstrated. For four ICDs, this would have caused the inappropriate
      delivery of a shock because of interference. At the end of the irradiation
      sessions, all devices had reached their point of failure. Complete loss of
      function was observed for four ICDs at dose levels between 0.5 Gy and 1.5 Gy.
      CONCLUSIONS: The effect of radiation therapy on the newest generation of ICDs
      varies widely. If tachycardia monitoring and therapy are functional (programmed
      on) during irradiation, the ICD might inappropriately give antitachycardia
      therapy, often resulting in a shock. Although most ICDs did not fail below 80 Gy,
      some devices had already failed at doses below 1.5 Gy. Guidelines are formulated
      for the treatment of patients with an ICD.

PMID- 16111599
TI  - An analysis of an implantable dosimeter system for external beam therapy.
AB  - BACKGROUND AND PURPOSE: To review the data from an implantable radiation
      dosimetry system used in a clinical setting and to examine correlations between
      dosimeter readings and potential causative error sources. MATERIALS AND METHODS:
      MOSFET (metal oxide semiconductor field effect transistor) based encapsulated
      dosimeters were evaluated in a phantom (in vitro) and in a study with 18
      patients. The dosimeters were placed in the gross tumor volume or in collateral
      normal tissue. Predicted dose values were established by imaging the dosimeters
      in the planning CTs. RESULTS: The in vitro study confirmed that bounding
      cumulative errors due to setup, planning, and machine output within a +/-5% level
      is achievable. In patients, it was found that deviations from the targeted dose
      often exceeded the 5% level. CONCLUSIONS: The use of an implantable dosimeter
      system could provide an effective empiric check on the dose delivered at depth.
      Such a tool may have value for institutional quality assurance, as well as for
      therapy delivered to individual patients.

PMID- 16111600
TI  - Intraoperative fluoroscopic dose assessment in prostate brachytherapy patients.
AB  - PURPOSE: To evaluate a fluoroscopy-based intraoperative dosimetry system to guide
      placement of additional sources to underdosed areas, and perform computed
      tomography (CT) verification. METHODS AND MATERIALS: Twenty-six patients with
      prostate carcinoma treated with either I-125 or Pd-103 brachytherapy at the Puget
      Sound VA using intraoperative postimplant dosimetry were analyzed. Implants were
      performed by standard techniques. After completion of the initial planned
      brachytherapy procedure, the initial fluoroscopic intraoperative dose
      reconstruction analysis (I-FL) was performed with three fluoroscopic images
      acquired at 0 (AP), +15, and -15 degrees. Automatic seed identification was
      performed and the three-dimensional (3D) seed coordinates were computed and
      imported into VariSeed for dose visualization. Based on a 3D assessment of the
      isodose patterns additional seeds were implanted, and the final fluoroscopic
      intraoperative dose reconstruction was performed (FL). A postimplant computed
      tomography (CT) scan was obtained after the procedure and dosimetric parameters
      and isodose patterns were analyzed and compared. RESULTS: An average of 4.7
      additional seeds were implanted after intraoperative analysis of the dose
      coverage (I-FL), and a median of 5 seeds. After implantation of additional seeds
      the mean V100 increased from 89% (I-FL) to 92% (FL) (p < 0.001). In I-125
      patients an improvement from 91% to 94% (p = 0.01), and 87% to 93% (p = 0.001)
      was seen for Pd-103. The D90 increased from 105% (I-FL) to 122% (FL) (p < 0.001)
      for I-125, and 92% (I-FL) to 102% (FL) (p = 0.008) for Pd-103. A minimal change
      occurred in the R100 from a mean of 0.32 mL (I-FL) to 0.6 mL (FL) (p = 0.19). No
      statistical difference was noted in the R100 (rectal volume receiving 100% of the
      prescribed dose) between the two techniques. The rate of adverse isodose patterns
      decreased between I-FL and FL from 42% to 8%, respectively. The I-125 patients
      demonstrated a complete resolution of adverse isodose patterns after the initial
      isodose reconstruction (I-FL). The Pd-103 patients demonstrated a final rate of
      8% gaps, 0% islands, and 0% holes on corrected isodose reconstruction.
      CONCLUSION: The use of intraoperative fluoroscopy-based dose assessment can
      accurately guide in the implantation of additional sources to supplement
      inadequately dosed areas within the prostate gland. Additionally, guided
      implantation of additional source, can significantly improve V100s and D90s,
      without significantly increasing rectal doses.

PMID- 16111601
TI  - Comparison of CT- and FDG-PET-defined GT: in regard to Paulino et al. (Int J
      Radiat Oncol Biol Phys 2005;61:1385-1392).

PMID- 16111602
TI  - In response to Drs. Anscher and Kong.

PMID- 16111603
TI  - In regard to Kagan: "The multidisciplinary clinic" (Int J Radiat Oncol Biol Phys
      2005;61:967-968).

PMID- 16111605
TI  - In regard to Marcie et al.: in vivo measurements with MOSFET detectors in
      oropharynx and nasopharynx intensity-modulated radiation therapy (Int J Radiat
      Oncol Biol Phys 2005;61:1603-1606).

PMID- 16111606
TI  - In regard to Lee et al.: "Dosimetry and cancer control after low-dose-rate
      prostate brachytherapy" (Int J Radiat Oncol Biol Phys 2005;61:52-59).

PMID- 16111609
TI  - A simple alpha/beta-independent method to derive fully isoeffective effective
      schedules following a change in dose per fraction: in regard to Joiner (Int J
      Radiat Oncol Biol Phys 2004;58:871-875).

PMID- 16111611
TI  - Echocardiographic findings using tissue velocity imaging following passive
      containment surgery with the Acorn CorCap cardiac support device.
AB  - OBJECTIVE: To echocardiographically evaluate the effects of passive containment
      surgery using the CorCap Cardiac Support Device in heart failure patients with
      dilated cardiomyopathy. METHODS: Twelve patients with dilated cardiomyopathy
      subjected to cardiac surgery received the Cardiac Support Device. Patients with
      ischemic cardiomyopathy (n=5) underwent coronary artery bypass surgery receiving
      1-3 bypass grafts. In the idiopathic cardiomyopathy group (n=7), mitral valve
      annuloplasty was performed in five patients while two patients received the
      Cardiac Support Device only. RESULTS: Following surgery there was a gradual,
      sustained improvement in cardiac dimensions (decreased left ventricular end
      diastolic diameter and left ventricular end-systolic diameter) combined with an
      increase in functional status (6-min walk and NYHA class). Concomitantly there
      was a marked decrease in right ventricular function (decrease in tricuspid
      annular systolic and diastolic velocities) while the left ventricular function
      (mitral annular systolic and diastolic velocities) and output (ejection fraction,
      stroke volume) remained unchanged. CONCLUSIONS: Addition of the Cardiac Support
      Device to conventional cardiac surgery improves patient status and decreases left
      ventricular size in heart failure patients with dilated cardiomyopathy. The
      positive effect on left ventricular dimensions is not accompanied by any
      improvement in cardiac output but rather right ventricular dysfunction, although
      the functional significance of this is unclear.

PMID- 16111612
TI  - Superficial ulnar artery.

PMID- 16111613
TI  - Early sternal erosion and luetic aneurysms of thoracic aorta: report of 6 cases
      and analysis of cause-effect relationship.
AB  - Six patients with luetic aneurysm of the ascending aorta eroding the sternum are
      presented. The erosion was an early and principal presentation and the site of
      erosion and location and morphology of aneurysm were identical in all six
      patients. The erosion mainly affected the right half of the manubrium and medial
      end of right clavicle. The aneurysms arose from the junction of the ascending and
      transverse arches of the thoracic aorta and had narrow opening close to the
      origin of the innominate artery. The identical presentation, aetiology,
      angiographic location and morphology, corroborated further at surgery, suggests
      that syphilitic aneurysms in this location have a strong tendency to cause early
      sternal erosion.

PMID- 16111614
TI  - Safety of complete median sternotomy approach for thymectomy.

PMID- 16111615
TI  - Arterial versus vein graft patency in coronary artery bypass grafting patients
      with ischemia-directed repeat angiography.

PMID- 16111617
TI  - Adolescents and media violence: six crucial issues for practitioners.
AB  - The mass media are rife with violent images and messages and youth spend a great
      deal of time with media. A rich tradition of research shows that exposure to
      media violence leads to aggressive thoughts, emotions, and behavior, and also to
      fear and desensitization. Certain youth are more vulnerable to violent media
      messages and images; the impact of media violence is modified by its nature and
      context. Parents, teachers, and the media industry should work toward mitigating
      the effects of media violence on youth; pediatricians and other health care
      providers play a key role in fostering healthy family media habits.

PMID- 16111618
TI  - Adolescents, sex, and the media: ooooo, baby, baby-a Q & A.
AB  - The media arguably have become the leading sex educator for American children and
      adolescents. More than 80% of the top teen shows contain sexual content, and the
      average teen views nearly 14,000 sexual references on television alone. The gap
      between suggestive and responsible content on primetime television is narrowing,
      but only slowly. Parents and teachers need to recognize the power of the media to
      educate and begin incorporating principles of media literacy into existing sex
      education programs.

PMID- 16111619
TI  - Body image and media use among adolescents.
AB  - This article reviews the literature on body image and media use among
      adolescents. We begin by defining body image and how it is constructed,
      especially among young people. We then offer information on when one's body image
      perception is askew with one's perception of personal ideal, which can result in
      disordered eating, including obesity, anorexia, and bulimia. Next, we describe
      the research literature on media use and its relationship to adolescents' body
      image perceptions and discuss content analyses and correlational, experimental,
      and qualitative studies. Lastly, we recommend, beyond conducting further and
      improved research studies, interventions and policies that may have an impact on
      body image and media use.

PMID- 16111620
TI  - Pornography and teenagers: the importance of individual differences.
AB  - This article focuses on the effects of exposure to pornography on teenagers,
      particularly males, and concentrates on sexually aggressive outcomes and on the
      characteristics of the individual as crucial in determining whether pornography
      consumption may or may not lead to sexually aggressive outcomes. In future work,
      it is important not to use an overly simplistic lens of focus in which
      pornography exposure is seen as generally harmful or not. Depending on particular
      constellations of personality characteristics, the effects of pornography may
      differ considerably among different teenagers as well as within different
      cultures. The research suggests that particular concerns may be needed for those
      who are highly frequent consumers of pornography, those who seek out sexually
      violent content, and those who also have other risk factors.

PMID- 16111621
TI  - Alcohol in the media: content and effects on drinking beliefs and behaviors among
      youth.
AB  - Drinking portrayals and alcohol advertising are common in popular media and young
      people are highly exposed to them. Although some studies found that exposure to
      drinking portrayals is related to increases in drinking among youth, other
      studies produced mixed and inconclusive findings. Similarly, research on the
      effects of alcohol advertising presents mixed findings. Recent longitudinal
      research and studies that used modeling techniques that controlled for reciprocal
      effects suggests that exposure to, attention to, and liking of alcohol
      advertising may influence children and adolescents' drinking beliefs and
      behaviors. Further research, and particularly longitudinal studies that address
      at-risk populations, such as children and minorities, is necessary before firm
      conclusions about the effects of media portrayals and alcohol advertising can be
      reached.

PMID- 16111622
TI  - Smoking in movies: impact on adolescent smoking.
AB  - This article examines the evidence that supports an association between seeing
      smoking depictions in movies and adolescent smoking. The portrayal of tobacco use
      is common in movies and often is modeled by stars, who, from a social influences
      standpoint, should be powerful behavior change agents. The results of studies
      that assess audience responses to tobacco portrayal in movies are remarkably
      consistent in showing a moderate to strong association between seeing movie
      smoking and more positive attitudes toward smoking and adolescent smoking
      initiation. The two published longitudinal studies show an independent link
      between exposure to movie smoking at baseline and initiation in the future, with
      estimates of the effect size being remarkably consistent with their cross
      sectional counterparts. Pediatricians should support public health campaigns to
      pressure the movie industry to voluntarily reduce smoking in movies and encourage
      parents to adhere to the Motion Picture Ratings System to reduce adolescent
      exposure to this powerful social influence to smoke.

PMID- 16111623
TI  - Video killed the radio star: the effects of music videos on adolescent health.
AB  - Since its inception half a century ago, rock and roll has been the music of youth
      and rebellion, of freedom, and of idealism. Popular music has been a reflection
      of, and inspiration for, youth movements, fads, and lifestyles that can include
      health risk behaviors, such as sex, drugs, and interpersonal violence. This
      article summarizes the health-related content of music videos, and discusses
      associations between music videos and adolescent health risks.

PMID- 16111624
TI  - Video games.
AB  - The video game industry insists that it is doing everything possible to provide
      information about the content of games so that parents can make informed choices;
      however, surveys indicate that ratings may not reflect consumer views of the
      nature of the content. This article describes some of the currently popular video
      games, as well as developments that are on the horizon, and discusses the status
      of research on the positive and negative impacts of playing video games.
      Recommendations are made to help parents ensure that children play games that are
      consistent with their values.

PMID- 16111625
TI  - Adolescents and the internet.
AB  - The interactive, multimedia nature of the Internet makes it a potentially
      invaluable resource for adolescents. These same characteristics also mean that
      the Internet could be a potentially hazardous medium for certain members of this
      age group. Although the Internet allows adolescents access to an unprecedented
      amount of content in an endless number of areas, it also allows them access to
      content that many parents and caregivers find particularly objectionable. This
      article addresses several primary benefits and potential hazards associated with
      adolescent Internet use. It describes general trends in adolescent Internet use
      and considers how the medium allows individuals to extend their social networks
      and create new ones. Several ideas for maximizing the potential benefits and
      minimizing any potential harms are presented.

PMID- 16111626
TI  - Media ratings for movies, music, video games, and television: a review of the
      research and recommendations for improvements.
AB  - This article review is organized by studies that are relevant for testing the
      reliability and validity of ratings systems. Specifically, the interrater
      reliability, consistency, temporal stability, content validity, construct
      validity, and criterion validity of media ratings systems are reviewed. Data that
      are related to testing the "forbidden fruit" and "tainted fruit" hypotheses also
      are reviewed. Several changes are recommended to improve the ratings systems,
      including the creation of a universal ratings system that could be applied
      equally to all media. The research reviewed here can provide a guide for how to
      construct a reliable, valid, and more useful ratings system. This is important
      because the decisions that parents make regarding their children's media use can
      be only as good as the information to which the parents have access.

PMID- 16111627
TI  - School commercialism and adolescent health.
AB  - Commercial activities in public schools are examined in light of growing concern
      over increasing rates of childhood obesity. The work and findings of the
      Education Policy Studies Laboratory, which documents school commercialism through
      media references, is detailed. Alongside evidence of increased commercialism,
      including activities that promote the consumption of unhealthful beverages and
      foods by students, growing public opposition to such activities also is
      documented. The argument is made that schoolhouse commercialism is not in the
      best interests of the health or the education of students.

PMID- 16111628
TI  - Adolescents and media literacy.
AB  - In the face of media industry consolidation, fewer people control media content
      which makes it harder for parents and citizens to know the research about media
      related issues, such as video game violence, nutrition, and sexual risk-taking.
      Media literacy offers a popular and potentially successful way to counter the
      misinformation that is spread by Big Media public relations.

PMID- 16111629
TI  - TLR ignores methylated RNA?
AB  - CpG methylation of DNA silences TLR9-mediated innate immune recognition. In this
      issue of Immunity, Kariko et al (2005) suggest that the innate immune recognition
      of RNA by TLR3, TLR7, or TLR8 is in fact controlled by modification of
      nucleotides, including methylation.

PMID- 16111630
TI  - Central tolerance matters.
AB  - In this issue of Immunity, Anderson et al. provide another clue to the riddle
      that is Aire--why do human beings and mice lacking Aire develop diffuse and
      pathogenic autoimmunity? They find that Aire influences central tolerance not
      only by promoting the expression of peripheral self-proteins in thymic medullary
      epithelial cells (MECs) but also by furnishing these cells with the apparatus for
      effective antigen presentation ().

PMID- 16111631
TI  - A comprehensive review of interventions in the NOD mouse and implications for
      translation.
AB  - Type 1 diabetes (T1D) animal models such as the nonobese diabetic (NOD) mouse
      have improved our understanding of disease pathophysiology, but many candidate
      therapeutics identified therein have failed to prevent/cure human disease. We
      have performed a comprehensive evaluation of disease-modifying agents tested in
      the NOD mouse based on treatment timing, duration, study length, and efficacy.
      Interestingly, some popular tenets regarding NOD interventions were not
      confirmed: all treatments do not prevent disease, treatment dose and timing
      strongly influence efficacy, and several therapies have successfully treated
      overtly diabetic mice. The analysis provides a unique perspective on NOD
      interventions and suggests that the response of this model to therapeutic
      interventions can be a useful predictor of the human response as long as careful
      consideration is given to treatment dose, timing, and protocols; more thorough
      investigation of these parameters should improve clinical translation.

PMID- 16111632
TI  - Novel role of the Ras cascade in memory B cell response.
AB  - Engagement of the B cell antigen receptor (BCR) triggers the Ras cascade, but the
      biological role of the latter in B cell response is unknown. Here, we report that
      in T cell-dependent response, the role of the Ras cascade is confined to memory B
      cells and possibly marginal zone B cells. When Ras-dependent BCR signaling was
      impaired, the generation of IgG germinal center B cells was unaffected but the
      recruitment of high-affinity cells into the memory compartment and terminal
      differentiation were inhibited. Furthermore, inhibition of MEK activity
      consistently impaired antibody production by IgG memory B cells (but not naive B
      cells) in vitro. Notably, this impairment was countered by overexpression of Bcl
      2. Thus, our data suggest that upon antigen stimulation, memory B cells are
      susceptible to apoptosis but can be rescued via an antiapoptotic effect mediated
      through the Ras cascade.

PMID- 16111633
TI  - CAML is a p56Lck-interacting protein that is required for thymocyte development.
AB  - Calcium modulating cyclophilin ligand (CAML) is a ubiquitously expressed protein
      implicated in T cell signaling, although its mechanism and physiologic role in
      the immune system are unknown. We show here that CAML is essential for peripheral
      T cell development. Inactivation of CAML in mouse thymocytes lowered the numbers
      of double-positive and single-positive thymocytes, concomitant with reduced
      positive and enhanced negative selection. We found that CAML interacts with
      p56Lck and appears to regulate subcellular localization of the kinase in both
      resting and T cell receptor (TCR)-stimulated cells. CAML-deficient cells
      displayed enhanced p56lck and ZAP-70 phosphorylation and increased IL2 production
      and cell death after TCR stimulation, suggesting that CAML may act as a negative
      regulator of p56lck. Our data establish a novel role for CAML as an essential
      mediator of T cell survival during thymopoiesis and indicate that its loss
      deregulates p56Lck signaling.

PMID- 16111634
TI  - Rules of recruitment for Th1 and Th2 lymphocytes in inflamed liver: a role for
      alpha-4 integrin and vascular adhesion protein-1.
AB  - The mechanisms that mediate the recruitment of Th1 and Th2 lymphocytes in vivo
      are poorly understood. We demonstrate that the mechanisms by which exogenously
      produced CD4(+) Th1 and Th2 cells roll and adhere in Con A-inflamed liver
      microcirculation differ dramatically: Th1 cells use alpha(4)beta(1)-integrin and
      Th2 cells use the vascular adhesion protein (VAP)-1. P-selectin plays no
      detectable role in Th1 or Th2 cell trafficking in liver microcirculation.
      Cellular recruitment in the liver sinusoids has previously been shown to be
      independent of many known adhesion molecules, leading to the suggestion that
      recruitment in these structures is mediated by physical trapping. While this may
      still be true for neutrophils, Th1 and Th2 cells use alpha(4)-integrin and VAP-1,
      respectively, to adhere within the liver sinusoids.

PMID- 16111635
TI  - Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside
      modification and the evolutionary origin of RNA.
AB  - DNA and RNA stimulate the mammalian innate immune system through activation of
      Toll-like receptors (TLRs). DNA containing methylated CpG motifs, however, is not
      stimulatory. Selected nucleosides in naturally occurring RNA are also methylated
      or otherwise modified, but the immunomodulatory effects of these alterations
      remain untested. We show that RNA signals through human TLR3, TLR7, and TLR8, but
      incorporation of modified nucleosides m5C, m6A, m5U, s2U, or pseudouridine
      ablates activity. Dendritic cells (DCs) exposed to such modified RNA express
      significantly less cytokines and activation markers than those treated with
      unmodified RNA. DCs and TLR-expressing cells are potently activated by bacterial
      and mitochondrial RNA, but not by mammalian total RNA, which is abundant in
      modified nucleosides. We conclude that nucleoside modifications suppress the
      potential of RNA to activate DCs. The innate immune system may therefore detect
      RNA lacking nucleoside modification as a means of selectively responding to
      bacteria or necrotic tissue.

PMID- 16111636
TI  - The Mnks are novel components in the control of TNF alpha biosynthesis and
      phosphorylate and regulate hnRNP A1.
AB  - Posttranscriptional regulatory mechanisms control TNFalpha expression through AU
      rich elements in the 3'UTR of its mRNA. This is mediated through Erk and p38 MAP
      kinase signaling, although the mechanisms involved remain poorly understood.
      Here, we show that the MAP kinase signal-integrating kinases (Mnks), which are
      activated by both these pathways, regulate TNFalpha expression in T cells via the
      3'UTR. A selective Mnk inhibitor or siRNA-mediated knockdown of Mnk1 inhibits
      TNFalpha production in T cells, whereas Mnk1 overexpression enhances expression
      of a reporter construct containing the TNFalpha 3'UTR. We identify ARE binding
      proteins that are Mnk substrates, such as hnRNP A1, which they phosphorylate at
      two sites in vitro. hnRNP A1 is phosphorylated in response to T cell activation,
      and this is blocked by Mnk inhibition. Moreover, Mnk-mediated phosphorylation
      decreases binding of hnRNP A1 to TNFalpha-ARE in vitro or TNFalpha-mRNA in vivo.
      Therefore, Mnks are novel players in cytokine regulation and potential new
      targets for anti-inflammatory therapy.

PMID- 16111637
TI  - Basophils play a critical role in the development of IgE-mediated chronic
      allergic inflammation independently of T cells and mast cells.
AB  - The recruitment of basophils into the sites of allergic inflammation is often
      observed. However, no definitive evidence has been provided that basophils are
      crucially involved in the pathogenesis of chronic allergic disorders. Here, we
      show that basophils are responsible for the development of IgE-mediated chronic
      allergic inflammation independently of T cells and mast cells. A single
      subcutaneous injection of multivalent antigens elicited not only immediate- and
      late-phase ear swelling but also delayed-onset ear swelling with massive
      eosinophil infiltration in mice sensitized with antigen-specific IgE. Mast cells
      were essential for the immediate- and late-phase ear swelling but dispensable for
      the delayed one. T cells were also dispensable for the latter. Transfer of FcRI
      expressing basophils into FcRI-deficient mice restored the development of the
      delayed-onset allergic inflammation. These findings indicate a novel mechanism of
      development of chronic allergic inflammation that is induced by basophils through
      the interaction of antigen, IgE, and FcRI.

PMID- 16111638
TI  - A direct interaction between the RAG2 C terminus and the core histones is
      required for efficient V(D)J recombination.
AB  - V(D)J recombination is a tightly controlled process of somatic recombination
      whose regulation is mediated in part by chromatin structure. Here, we report that
      RAG2 binds directly to the core histone proteins. The interaction with histones
      is observed in developing lymphocytes and within the RAG1/RAG2 recombinase
      complex in a manner that is dependent on the RAG2 C terminus. Amino acids within
      the plant homeo domain (PHD)-like domain as well as a conserved acidic stretch of
      the RAG2 C terminus that is considered to be a linker region are important for
      this interaction. Point mutations that disrupt the RAG2-histone association
      inhibit the efficiency of the V(D)J recombination reaction at the endogenous
      immunoglobulin locus, with the most dramatic effect in the V to DJ(H)
      rearrangement.

PMID- 16111639
TI  - Protein kinase D1 and the beta 1 integrin cytoplasmic domain control beta 1
      integrin function via regulation of Rap1 activation.
AB  - The functional activity of integrins is dynamically regulated by T cell receptor
      stimulation and by protein kinase C (PKC). We report a novel function for the PKC
      effector protein kinase D1 (PKD1) in integrin activation. Constitutively active
      and kinase-inactive PKD1 mutants lacking the PKD1 pleckstrin homology (PH) domain
      block phorbol ester- and TCR-mediated activation and clustering of beta1
      integrins. The PH domain of PKD1 mediates the association of PKD1 with the GTPase
      Rap1 and is central to Rap1 activation and membrane translocation in T cells.
      Furthermore, PKD1 and Rap1 associate with beta1 integrins in a manner that is
      dependent on the carboxy-terminal end of the beta1 integrin subunit cytoplasmic
      domain. beta1 integrin expression is required for Rap1 activation and membrane
      localization of the PKD1-Rap1 complex. Therefore, PKD1 promotes integrin
      activation in T cells by regulating Rap1 activation and membrane translocation
      via interactions with the beta1 integrin subunit cytoplasmic domain.

PMID- 16111640
TI  - The cellular mechanism of Aire control of T cell tolerance.
AB  - Aire promotes the tolerization of thymocytes by inducing the expression of a
      battery of peripheral-tissue antigens in thymic medullary epithelial cells. We
      demonstrate that the cellular mechanism by which Aire exerts its tolerance
      promoting function is not primarily positive selection of regulatory T cells, but
      rather negative selection of T effector cells. Surprisingly, supplementing its
      influence on the transcription of genes encoding peripheral-tissue antigens, Aire
      somehow enhances the antigen-presentation capability of medullary epithelial
      cells. Thus, this transcriptional control element promotes central tolerance both
      by furnishing a specific thymic stromal cell type with a repertoire of self
      antigens and by better arming such cells to present these antigens to
      differentiating thymocytes. In Aire's absence, autoimmunity and ultimately overt
      autoimmune disease develops.

PMID- 16111641
TI  - Trends in spinal cord injury.
AB  - This study reports on trends in spinal cord injury based on the Australian Spinal
      Cord Injury Register (ASCIR), which provided full coverage in those aged 15 years
      and over. The underlying annual rate of change from 1986 to 1997 was calculated
      for age-specific, crude and age-standardised incidence rates. An appropriate
      model for this type of data was the Poisson regression model, with a Poisson
      error distribution, a log link function and the natural log of population treated
      as an 'offset'. It was found that there was no change in the age-standardised
      rate of spinal cord injury. However, an assessment of specific rates by age, sex,
      cause and neurological group revealed some contrasting trends, notably declining
      rates in young males, transport-related injury and complete tetraplegia, and
      increasing rates in elderly males, fall-related injury and incomplete tetraplegia
      and complete paraplegia. These changes are considered to reflect the impact of a
      raft of public health measures directed at transport-related injury but a paucity
      of prevention programs directed at fall-related spinal cord injury. More research
      is required to determine the causes of the increasing rate of elderly male fall
      related spinal cord injury. There is also more that can be done to prevent
      transport-related spinal cord injury. Sport utility vehicles pose an increased
      concern. In order to reinvigorate the debate about the need for a vehicle
      rollover resistance rating in Australia, the spinal cord injury risk of different
      models of SUV should be measured. This has already been implemented in the United
      States, providing the public with information to assist purchasing based on
      safety considerations.

PMID- 16111642
TI  - Polymer based interfaces as bioinspired 'smart skins'.
AB  - This work reports on already achieved results and ongoing research on the
      development of complex interfaces between humans and external environment, based
      on organic synthetic materials and used as smart 'artificial skins'. They are
      conceived as wearable and flexible systems with multifunctional characteristics.
      Their features are designed to mimic or augment a broad-spectrum of properties
      shown by biological skins of humans and/or animals. The discussion is here
      limited to those properties whose mimicry/augmentation is achievable with
      currently available technologies based on polymers and oligomers. Such properties
      include tactile sensing, thermal sensing/regulation, environmental energy
      harvesting, chromatic mimetism, ultra-violet protection, adhesion and surface
      mediation of mobility. Accordingly, bioinspired devices and structures, proposed
      as suitable functional analogous of natural architectures, are analysed. They
      consist of organic piezoelectric sensors, thermoelectric and pyroelectric sensors
      and generators, photoelectric generators, thermal and ultra-violet protection
      systems, electro-, photo- and thermo-chromic devices, as well as structures for
      improved adhesion and reduced fluid-dynamic friction.

PMID- 16111643
TI  - Profiling oligosaccharidurias by electrospray tandem mass spectrometry:
      quantifying reducing oligosaccharides.
AB  - A method to semiquantify urinary oligosaccharides from patients suffering from
      oligosaccharidurias is presented. 1-Phenyl-3-methyl-5-pyrazolone has been used to
      derivatize urinary oligosaccharides prior to analysis by electrospray ionization
      tandem mass spectrometry (ESI-MS/MS). Disease-specific oligosaccharides were
      identified for several oligosaccharidurias, including GM1 gangliosidosis, GM2
      gangliosidosis, sialic acid storage disease, sialidase/neuraminidase deficiency,
      galactosialidosis, I-cell disease, fucosidosis, Pompe and Gaucher diseases, and
      alpha-mannosidosis. The oligosaccharides were referenced against the internal
      standard, methyl lactose, to produce ratios for comparison with control samples.
      Elevations in specific urinary oligosaccharides were indicative of lysosomal
      disease and the defective catabolic enzyme. This method has been adapted to
      enable assay of large sample numbers and could readily be extended to other
      oligosaccharidurias and to monitor oligosaccharide levels in patients receiving
      treatment. It also has immediate potential for incorporation into a newborn
      screening program.

PMID- 16111644
TI  - Inactivation of GDP-mannose dehydrogenase from Pseudomonas aeruginosa by
      penicillic acid identifies a critical active site loop.
AB  - The pathogenic bacterium Pseudomonas aeruginosa synthesizes alginate as one of a
      group of virulence factors that are produced during infections. The enzyme GDP
      mannose dehydrogenase catalyzes the committed step in alginate biosynthesis. We
      show here that penicillic acid is an irreversible inactivator of GDP-mannose
      dehydrogenase. Inactivation occurs with a rate constant of 0.39+/-0.01 mM(-1)
      min(-1) at pH 8.0, and does not exhibit saturation behavior. Partial protection
      from inactivation is afforded by GDP-mannose, but not by the other substrate,
      NAD+. GMP and NAD+ together provide complete protection against inactivation.
      Analysis by mass spectrometry confirmed that the enzyme is alkylated at multiple
      cysteine residues by penicillic acid, including Cys 213, Cys 246, and the active
      site cysteine, Cys 268. However, the pH dependence of the inactivation rate
      suggested that alkylation of a single cysteine residue is sufficient to
      inactivate the enzyme. The C268A mutant protein was also susceptible to
      inactivation by penicillic acid. The presence of NAD+ and GMP provided partial
      protection of Cys 246 and Cys 268, and almost complete protection of Cys 213. Cys
      213 is located on a helix that forms part of the binding pocket for GDP-mannose,
      and forms a hydrogen bond with Asn 252. Asn 252 is located on a loop that
      surrounds GDP-mannose. The C213A mutant enzyme exhibits a Vmax that is 1.8-fold
      greater than the wild-type enzyme, suggesting that the interaction between Cys
      213 and Asn 252 helps to hold the loop in place during catalysis, and that
      opening the loop to release product is partially rate-limiting. Cys 246 is
      adjacent to the GDP-mannose binding loop, and its alkylation may also interfere
      with loop movement.

PMID- 16111645
TI  - Quantitative structure-activity relationships in prooxidant cytotoxicity of
      polyphenols: role of potential of phenoxyl radical/phenol redox couple.
AB  - The aim of this work was to characterize the role of the potential of phenoxyl
      radical/phenol redox couple, E(7)(2), in the cytotoxicity of polyphenols. The
      cytotoxicity of polyphenols in bovine leukemia virus-transformed lamb kidney
      fibroblasts (line FLK), and human promyelocytic leukemia cells (line HL-60) was
      partly inhibited by catalase, by the antioxidant N,N'-diphenyl-p-phenylene
      diamine and desferrioxamine, and potentiated by 1,3-bis-(2-chloro-ethyl)-1
      nitrosourea, thus showing its prooxidant character. Dapsone, an inhibitor of
      myeloperoxidase, did not affect the cytotoxicity of polyphenols in HL-60 cells,
      whereas dicumarol, an inhibitor of DT-diaphorase, showed controversial effects on
      their cytotoxicity in FLK cells. Inhibitors of cytochromes P-450, alpha
      naphthoflavone and izoniazide, decreased the cytotoxicity of several polyphenols,
      whereas 3,5-dinitrocatechol, an inhibitor of catechol-o-methyltransferase (COMT),
      increased it. The cytotoxicity of 13 polyhydroxybenzenes was described by the
      equations: logcL50 (microM) = -0.67 + 5.46E(7)(2) (V) - 0.16 logD (FLK), and
      logcL50 (microM) = -1.39 + 6.90E(7)(2) (V) - 0.20logD (HL-60), where cL50 is
      compound concentration for 50% cell survival, and D is octanol/water distribution
      coefficient at pH 7.0. The flavonoids comprise a separate series of compounds
      with lower cytotoxicity. The correlations obtained quantitatively confirm the
      parallelism between the polyphenol cytotoxicity and the rates of their single
      electron oxidation, and point to the leading role of formation of the reactive
      oxygen species in their cytotoxicity. Depending on the examined system, this
      parallelism may be distorted due to the cytochrome P-450 and COMT-catalyzed
      transformation of polyphenols.

PMID- 16111646
TI  - Effect of N-terminal deletions on the foldability, stability, and activity of
      staphylococcal nuclease.
AB  - The effect of N-terminally successive deletions on the foldability, stability,
      and activity of staphylococcal nuclease was examined. The structural changes in
      the nuclease caused by the deletions follow a hierarchical pattern: N-terminal
      truncation of the nuclease by up to nine residues clearly perturbs the
      conformation of the N-terminal beta-subdomain but does not affect the C-terminal
      alpha-subdomain; deletion of 11 or 12 residues perturbs the C-terminal alpha
      subdomain, resulting in formation of a molten globule state; deletion of 13
      residues causes the nuclease to become highly unfolded. N-terminally deleted
      nuclease delta11 retains the ability to fold but delta12 is not able to fold into
      an enzymatically active conformation, suggesting that 11 residues is the maximum
      length that can be deleted from the N-terminus while still retaining the folding
      competence of the nuclease. Further, the results suggest that proper folding of
      the C-terminal alpha-subdomain probably relies on the integrity of the N-terminal
      beta-subdomain.

PMID- 16111647
TI  - Origin, structure, and biological activities of peroxidases in human saliva.
AB  - Human whole saliva contains two peroxidases, salivary peroxidase (hSPO) and
      myeloperoxidase (hMPO), which are part of the innate host defence in oral cavity.
      Both hSPO as well as human milk lactoperoxidase (hLPO) are coded by the same
      gene, but to what extent the different producing glands, salivary and mammary
      glands, affect the final conformation of the enzymes is not known. In human
      saliva the major function of hSPO and hMPO is to catalyze the oxidation of
      thiocyanate (SCN(-)) in the presence of hydrogen peroxide (H(2)O(2)) resulting in
      end products of wide antimicrobial potential. In addition cytotoxic H(2)O(2) is
      degraded. Similar peroxidation reactions inactivate some mutagenic and
      carcinogenic compounds, which suggests another protective mechanism of
      peroxidases in human saliva. Although being target of an active antimicrobial
      research, the structure-function relationships of hSPO are poorly known. However,
      recently published method for recombinant hSPO production offers new tools for
      those investigations.

PMID- 16111648
TI  - The modulation of thiol redox state affects the production and metabolism of
      hydrogen peroxide by heart mitochondria.
AB  - In rat heart mitochondria, auranofin, arsenite, diamide, and BCNU increase H2O2
      formation, further stimulated by antimycin. However, in submitochondrial
      particles, H2O2 formation and oxygen uptake are not affected, indicating that
      these substances do not alter respiration. Mitochondria are also able to rapidly
      metabolize added H2O2 in a process partially prevented by BCNU or auranofin.
      Calcium does not modify the production of H2O2 and the mitochondrial thioredoxin
      system is not affected by calcium ions. Auranofin, arsenite, and diamide
      determine a large mitochondrial permeability transition, while BCNU and
      acetoacetate are ineffective. Thiols and glutathione are modified only by BCNU
      and diamide. However, all the compounds tested cause the release of cytochrome c
      that occurs also in the absence of mitochondrial swelling. In conclusion, the
      compounds utilized share the common feature of shifting the mitochondrial thiol
      linked redox balance towards a more oxidized condition that is responsible of the
      observed effects.

PMID- 16111649
TI  - Formation of reactive halide species by myeloperoxidase and eosinophil
      peroxidase.
AB  - The formation of chloro- and bromohydrins from 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine following incubation with myeloperoxidase or eosinophil peroxidase
      in the presence of hydrogen peroxide, chloride and/or bromide was analysed by
      matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry.
      These products were only formed below a certain pH threshold value, that
      increased with increasing halide concentration. Thermodynamic considerations on
      halide and pH dependencies of reduction potentials of all redox couples showed
      that the formation of a given reactive halide species in halide oxidation coupled
      with the reduction of compound I of heme peroxidases is only possible below a
      certain pH threshold that depends on halide concentration. The comparison of
      experimentally derived and calculated data revealed that Cl(2), Br(2), or BrCl
      will primarily be formed by the myeloperoxidase-H(2)O(2)-halide system. However,
      the eosinophil peroxidase-H(2)O(2)-halide system forms directly HOCl and HOBr.

PMID- 16111650
TI  - A novel Arnt-interacting protein Ainp2 enhances the aryl hydrocarbon receptor
      signalling.
AB  - In an effort to better understand the Ah receptor nuclear translocator (Arnt)
      dependent signaling mechanisms, we employed a phage display system to identify
      Arnt-interacting peptides. Human liver cDNA library was utilized to screen for
      Arnt-interacting peptides using an Arnt construct fused to thioredoxin (TH
      ArntCDelta418). Two clones, namely Ainp1 and Ainp2 (Arnt-interacting peptide),
      were identified and subsequently Ainp2 was further characterized. Ainp2 interacts
      with TH-ArntCDelta418 in the GST pull-down and mammalian two-hybrid assays.
      Northern blot results revealed that Ainp2 is predominantly expressed in human
      liver. The putative full-length Ainp2 cDNA sequence was subsequently cloned using
      RACE PCR. Endogenous expression of Ainp2 was found in Jurkat cells at the mRNA
      and protein levels. Results from the transient transfection studies using a DRE
      driven reporter plasmid and the real-time QPCR experiments examining the
      endogenous CYP1A1 expression showed that Ainp2 enhances the 3-methylchloranthrene
      induced activity in HepG2 cells, suggesting that Ainp2 plays a role in the Arnt
      dependent function

PMID- 16111652
TI  - A comprehensive model of positional and stereo control in lipoxygenases.
AB  - The lipoxygenase gene family can synthesize an array of chiral hydroperoxy
      derivatives from polyunsaturated fatty acids. An individual enzyme, however,
      reacts molecular oxygen on a single position on the carbon chain and in a single
      stereo configuration. Regiospecificity is regulated by the orientation and depth
      of substrate entry into the active site. Stereospecificity is a different issue
      and only recently has experimental support emerged to explain the conceptual
      basis of stereo control. A key determinant is a single active site residue
      conserved as an Ala in S lipoxygenases and a Gly in R lipoxygenases; this residue
      controls R or S stereochemistry by switching the position of oxygenation on the
      reacting pentadiene of the substrate. In this review, we meld together the
      factors that control product regio- and stereochemistry into a general model that
      can account for the specificity of individual lipoxygenase reactions.

PMID- 16111653
TI  - Reactivity of a new class of P450 enzyme models.
AB  - P450 enzyme models carrying a SO3(-) ligand coordinating to iron have been
      synthesized and characterized. These complexes show characteristics very similar
      to those of iron-heme cofactors of P450 enzymes. Their reactivity towards
      different reactions catalyzed by P450 enzymes such as epoxidation of double
      bonds, hydroxylation of non-activated C-H bonds, N-dealkylation of amines, and
      cleavage of diols (C-C-bond cleavage) has been investigated.

PMID- 16111654
TI  - Role of c-Jun in cellular sensitivity to the microtubule inhibitor vinblastine.
AB  - The role of c-Jun in the apoptotic response of cells to the microtubule inhibitor
      vinblastine was investigated using fibroblasts lacking or overexpressing c-Jun. c
      Jun null cells were found to be more sensitive than wild-type cells at low (1-3
      nM) concentrations of vinblastine, but showed essentially identical apoptotic
      responses as wild-type cells at a higher concentration of 10nM. In contrast, c
      Jun overexpressing cells were highly vinblastine-resistant, with an IC50 of 12
      fold greater than wild-type cells. The fate of cells exposed to lethal
      concentrations of vinblastine was examined by propidium iodide staining and flow
      cytometry. All cell types appeared to undergo mitotic arrest prior to apoptosis.
      Apoptosis of wild-type cells was associated with significant DNA re-replication.
      In contrast, DNA re-replication was much less prominent in vinblastine-treated c
      Jun null cells and absent during apoptosis of c-Jun overexpressing cells. These
      results suggest that c-Jun plays a key role in the cellular sensitivity to
      vinblastine. In addition, c-Jun appears to regulate the pathway to cell death
      following mitotic arrest.

PMID- 16111655
TI  - Lysophosphatidic acid mediates pleiotropic responses in skeletal muscle cells.
AB  - Lysophosphatidic acid (LPA) is a potent modulator of growth, cell survival, and
      apoptosis. Although all four LPA receptors are expressed in skeletal muscle, very
      little is known regarding the role they play in this tissue. We used RT-PCR to
      demonstrate that cultured skeletal muscle C2C12 cells endogenously express
      multiple LPA receptor subtypes. The demonstration that LPA mediates the
      activation of ERK1/2 MAP kinase and Akt/PKB in C2C12 cells is consistent with the
      widely observed mitogenic properties of LPA. In spite of these observations, LPA
      did not induce proliferation in C2C12 cells. Paradoxically, we found that
      prolonged treatment of C2C12 cells with LPA led to caspase 3 and PARP cleavage as
      well as the activation of stress-associated MAP kinases JNK and p38. In spite of
      these typically pro-apoptotic responses, LPA did not induce cell death. Blocking
      ERK1/2 and Akt/PKB activation with specific pharmacological inhibitors,
      nevertheless, stimulated LPA-mediated apoptosis. Taken together, these results
      suggest that both mitogenic and apoptotic responses serve to counterbalance the
      effects of LPA in cultured C2C12 cells.

PMID- 16111656
TI  - Death of osteocytes turns off the inhibition of osteoclasts and triggers local
      bone resorption.
AB  - Osteocytes have been suggested to play a role in the regulation of bone
      resorption, although their effect on bone turnover has remained controversial. In
      order to study this open question, we developed an organ culture system based on
      isolated rat calvaria, where the osteocyte viability and its effect on
      osteoclastic bone resorption can be monitored. Our results suggest that
      osteocytes are constitutively negative regulators of osteoclastic activity.
      Osteoclasts, which were cultured on calvarial slices with living osteocytes
      inside, failed to form actin rings which are the hallmarks of resorbing cells. A
      similar inhibitory effect was also achieved by the conditioned medium obtained
      from calvarial organ culture, suggesting that living osteocytes produce yet
      unrecognized osteoclast inhibitors. On the contrary, when osteocyte apoptosis was
      induced, this inhibitory effect disappeared and strong osteoclastic bone
      resorption activity was observed. Thus, local apoptosis of osteocytes may play a
      major role in triggering local bone remodeling.

PMID- 16111657
TI  - Isolation of mannose-binding C-type lectin from Heliothis virescens pupae.
AB  - A mannose-binding C-type lectin (MBL) was isolated by affinity chromatography
      from Heliothis virescens immune pupal hemolymph. The immune pupal hemolymph was
      obtained after bacterial injection of live Enterobacter cloacae bacteria. MBL in
      mammals acts as an opsonin for phagocytosis and activates the lectin complement
      pathway of the innate immune response, which leads to killing of gram-negative
      bacteria and enveloped viruses. The affinity-purified and reduced pupal MBL
      showed a single band of 36 kDa by SDS-PAGE (12% gel). A dot-immunoblot ELISA
      (using guinea pig anti-MBL IgG as primary antibody) demonstrated specificity of
      the antibody for the affinity-purified pupal MBL. The immune pupal hemolymph
      contained 21 microg of MBL per ml of hemolymph. The amino acid composition of the
      purified pupal MBL was determined with high amounts of arginine and histidine
      detected. The presence of MBL in insect pupae has not before been reported and
      could be important in pupal innate immunity to bacterial infection.

PMID- 16111658
TI  - Stable inhibition of hepatitis B virus expression and replication by expressed
      siRNA.
AB  - RNA interference might be an efficient antiviral therapy for some obstinate
      illness. Here, we studied the effects of hepatitis B virus (HBV)-specific 21-nt
      small interfering RNAs (siRNA) on HBV gene expression and replication in 2.2.15
      cells. Seven vectors expressing specific hairpin siRNA driven by the RNA
      polymerase II-promoter were constructed and transfected into 2.2.15 cells. In the
      cell strain that can stably express functional siRNA, the HBV surface antigen
      (HBsAg) and the HBV e antigen (HBeAg) secretion into culture media was inhibited
      by 86% and 91%, respectively, as shown by an enzyme-linked immunosorbent assay.
      Immunofluorescence and Western blot indicated similar results. HBV DNA was
      markedly restrained by 3.28-fold, as assessed by the fluorescent quantitation
      PCR. Moreover, the HBV mRNA was significantly reduced by 80% based on
      semiquantitative RT-PCR. In conclusion, the specific siRNA can knock down the HBV
      gene expression and replication in vitro, and the silence effects have no
      relationship with interferon response.

PMID- 16111659
TI  - Coil-to-helix transition and ligand release of Bombyx mori pheromone-binding
      protein.
AB  - The transport of hydrophobic insect pheromones through the aqueous medium
      surrounding their receptors is assisted by pheromone-binding proteins (PBPs). The
      protein from the silkworm moth Bombyx mori, BmorPBP, exhibits a pH-dependent
      conformational change postulated to trigger the release of the pheromone bombykol
      to its receptor. At low pH, an alpha-helix occupies the same binding pocket that
      houses the pheromone in the BmorPBP-bombykol complex at high pH. We have
      determined the crystal structure of apo BmorPBP at a resolution of 2.3 angstroms
      and pH 7.5, which has surprisingly a structure similar to the A-form. These data
      suggest that BmorPBP undergoes a ligand-dependent conformational change in
      addition to the previously described pH-dependent conformational change. Analysis
      of the alpha-helix occupying the binding pocket reveals an amphipathic helix with
      three acidic residues along one face that are conserved among lepidopteran PBPs
      and may be involved in a conformational transition of BmorPBP at the receptor
      membrane.

PMID- 16111660
TI  - Deduction of upstream sequences of Xanthomonas campestris flagellar genes
      responding to transcription activation by FleQ.
AB  - Xanthomonas campestris pv. campestris (Xcc), a close relative to Pseudomonas
      aeruginosa, is the pathogen causing black rot in cruciferous plants. In P.
      aeruginosa, FleQ serves as a cognate activator of sigma54 in transcription from
      several sigma54-dependent promoters of flagellar genes. These P. aeruginosa
      promoters have been analyzed for FleQ-binding sequences; however, no consensus
      was deduced. Xcc, although lacks fleSR, has a fleQ homologue residing among over
      40 contiguously clustered flagellar genes. A fleQ mutant, Xc17fleQ, constructed
      by insertional mutation is deficient in FleQ protein, non-flagellated, and
      immobile. Transcriptional fusion assays on six putative sigma54-dependent
      promoters of the flagellar genes, fliE, fliQ, fliL, flgG, flgB, and flhF,
      indicated that each of them is also FleQ dependent. Each of these promoters has a
      sequence with weak consensus to 5'-gaaacCCgccgCcgctTt-3', immediately upstream of
      the predicted sigma54-binding site, with an imperfect inverted repeat containing
      a GC-rich center flanked by several A and T at 5'- and 3'-ends, respectively.
      Replacing this region in fliE promoter with a HindIII recognition sequence
      abolished the transcription, indicating that this region responds to
      transcription activation by FleQ.

PMID- 16111661
TI  - Rapid spinogenesis of pyramidal neurons induced by activation of glucocorticoid
      receptors in adult male rat hippocampus.
AB  - Modulation of hippocampal synaptic plasticity by glucocorticoids has been
      attracting much attention, due to its importance in stress responses. Dendritic
      spines are essential for memory storage processes. Here, we investigated the
      effect of dexamethasone (DEX), a specific agonist of glucocorticoid receptor
      (GR), on density and morphology of dendritic spines in adult male rat hippocampus
      by imaging of Lucifer Yellow-injected spines in slices. The application of 100 nM
      DEX (stressful high concentration) induced rapid modulation of the density and
      morphology of dendritic spines in CA1 pyramidal neurons within 1h. The total
      spine density increased from 0.88 spines/microm (control) to 1.36 spines/microm
      (DEX-treated). DEX significantly increased the density of thin and mushroom type
      spines, however only a slight increase was observed for stubby and filopodium
      type spines. Because the presence of 10 microM cycloheximide, an inhibitor of
      protein synthesis, did not suppress the DEX effect, these responses are probably
      non-genomic. Western immunoblot analysis demonstrated the localization of
      classical type GR in Triton-insoluble synaptosomal fractions (enriched in
      postsynaptic membranes) from hippocampal slices, suggesting a possible action
      site of DEX at spines.

PMID- 16111662
TI  - Functional analysis of TatA and TatB in Streptomyces lividans.
AB  - Recently, genes encoding TatA, TatB, and TatC homologues were identified in
      Streptomyces lividans and the functionality of the twin-arginine translocation
      (Tat) pathway was demonstrated. Previously, we have shown that TatC is
      indispensable for Tat-dependent secretion in S. lividans. In the present work, we
      demonstrate that as TatB, S. lividans TatA is important but not essential for
      efficient secretion of xylanase C and tyrosinase. The results presented here
      indicate that in the presence of TatC, still partially functional translocation
      systems composed of TatAC or TatBC can be formed, suggesting that TatA and TatB
      have at least partially overlapping activities. However, the dissimilar effect
      caused by a tatA deletion or a tatB deletion on Tat-dependent secretion together
      with the fact that TatA cannot fully functionally substitute TatB and vice versa
      indicates that in S. lividans TatA and TatB are not functionally equivalent.
      Interestingly, soluble GST-tagged TatA and TatB were able to specifically bind
      Tat-dependent preproteins. The ability to bind Tat-dependent preproteins together
      with their cytoplasmic localization in S. lividans strongly suggests that both
      TatA and TatB, independently or associated, serve to recruit Tat-dependent
      preproteins to the translocase.

PMID- 16111663
TI  - A facile synthesis of the GalNAcbeta1-->4Gal target sequence of respiratory
      pathogens.
AB  - The carbohydrate sequence, GalNAcbeta1-->4Gal, is the target for the adhesion of
      several respiratory pathogens. The sequence was prepared in an optimized
      synthesis in forms that allow conjugation to scaffolds or surfaces.

PMID- 16111664
TI  - Local statin therapy differentially interferes with smooth muscle and endothelial
      cell proliferation and reduces neointima on a drug-eluting stent platform.
AB  - OBJECTIVE: Therapeutic strategies to provide local inhibition of mitogen mediated
      proliferation and migration of human coronary artery smooth muscle cells (CASMC)
      by means of drug-eluting stents have been shown to enable effective limitation of
      neointimal hyperplasia. However, currently available drug-eluting stents utilize
      compounds that may also adversely affect endothelial regrowth, thus possibly
      precipitating subsequent cardiac events. Accordingly, identification of compounds
      that differentially inhibit smooth muscle and endothelial cell migration and
      proliferation could be of substantial clinical usefulness. METHODS AND RESULTS:
      In addition to lipid lowering, statins are known to display auxiliary pleiotropic
      activities. The purpose of this study was to evaluate the effect of local
      administration of cerivastatin on proliferation, migration and cytotoxicity of
      CASMC as well as coronary artery endothelial cells (CAEC) and to evaluate the
      effect of cerivastatin-coated stents on the inhibition of neointima formation as
      well as endothelial regrowth within the stented vessel. Cerivastatin displayed a
      differential effect on CASMC as compared to CAEC with regard to proliferation and
      migration; both were more profoundly inhibited in CASMC. Appreciable cytotoxicity
      and pro-apoptotic effects were low in both cell lines at therapeutic
      concentrations. Cerivastatin-elution led to significant inhibition of neointima
      formation in the rat carotid stent model, endothelial coverage of in-stent
      vascular tissue was similar with control and cerivastatin-eluting stents.
      CONCLUSIONS: As proof of principle, our study provides evidence that local
      application of a HMG-CoA reductase inhibitor on a drug-eluting stent platform can
      efficiently limit neointima formation. Consequently, these compounds warrant
      further clinical evaluation to confirm this finding. Our data further suggest
      that the anti-restenotic effect of local statin administration might be
      associated with a more protective interaction with the endothelium than that
      observed with compounds currently employed on drug-eluting stents.

PMID- 16111665
TI  - Non-capacitative calcium entry--extension of the possibilities for calcium entry
      in vascular tissue.

PMID- 16111666
TI  - Lipoprotein[a] and the lipid profile in patients with systemic sclerosis.
AB  - BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disorder of the connective
      tissue characterized by widespread vascular lesions and fibrosis, associated with
      endothelial dysfunction, that might finally promote occlusive vascular
      complications. Little is known so far on the lipid profile of these patients.
      METHODS: To investigate the potential contribution of lipid abnormalities in
      genesis and progression of vascular occlusive complications, an extensive lipid
      profile, including total cholesterol, low-density lipoprotein cholesterol, high
      density lipoprotein cholesterol, triglycerides, total cholesterol to HDL-C ratio,
      the atherogenic index of plasma, lipoprotein[a] (Lp[a]) and high-sensitive C
      Reactive Protein (Hs-CRP), was assessed in 31 consecutive female SSc patients and
      33 matched healthy controls. RESULTS: When compared to healthy matched controls,
      SSc patients displayed statistically significant differences in median and 25
      75th percentile distribution of Lp[a] (110 mg/l, 51-389 mg/l vs. 79 mg/l, 29-149
      mg/l; P =0.005) and in the mean concentration of Hs-CRP (4.49 +/- 5.06 mg/l vs.
      1.36 +/- 1.19 mg/l; P =0.001), but not in the other lipid parameters. When
      compared to the current NCEP or AHA/ACC goals, the values distributions and the
      relative percentage of patients with undesirable or abnormal vales were
      statistically different for Lp[a] (29% versus 3%) and Hs-CRP (42% vs. 12%) (both
      P <0.001). CONCLUSIONS: If further studies will strengthen these preliminary
      findings, owing to the growing evidence that Lp[a] might act in synergy with
      other defined prothrombotic conditions in the pathogenesis of a variety of
      vascular disorders, we hypothesize that Lp[a] measurement might be useful in SSc
      to identify and eventually treat subsets of patients more predisposed to develop
      thrombotic complications.

PMID- 16111667
TI  - Real-time assays with molecular beacons and other fluorescent nucleic acid
      hybridization probes.
AB  - BACKGROUND: A number of formats for nucleic acid hybridization have been
      developed to identify DNA and RNA sequences that are involved in cellular
      processes and that aid in the diagnosis of genetic and infectious diseases.
      METHODS: The introduction of hybridization probes with interactive fluorophore
      pairs has enabled the development of homogeneous hybridization assays for the
      direct identification of nucleic acids. A change in the fluorescence of these
      probes indicates the presence of a target nucleic acid, and there is no need to
      separate unbound probes from hybridized probes. CONCLUSIONS: The advantages of
      homogeneous hybridization assays are their speed and simplicity. In addition,
      homogeneous assays can be combined with nucleic acid amplification, enabling the
      detection of rare target nucleic acids. These assays can be followed in real
      time, providing quantitative determination of target nucleic acids over a broad
      range of concentrations.

PMID- 16111668
TI  - Plasma homocysteine thiolactone adducts associated with risk of coronary heart
      disease.
AB  - BACKGROUND: Homocysteine thiolactone adducts have been proposed as the culprit of
      homocysteine related cardiovascular diseases. We studied the association of these
      adducts in plasma, and the gene polymorphism of paraoxonase-2 with coronary heart
      disease. METHODS: 254 patients and 308 controls were recruited for the study.
      Homocysteine thiolactone adducts were determined with ELISA. The codon 311
      polymorphism of paraoxonase-2 gene was genotyped by using polymerase chain
      reaction and restrictive digestion. RESULTS: The plasma level of homocysteine
      thiolactone adducts were significantly higher in patients than in controls (40.65
      +/- 10.87 u/ml vs. 30.58 +/- 10.20 u/ml, P <0.01), with odds ratio of 7.34 (95%
      confidence interval 4.020-13.406, P <0.01), and increased according to the number
      of atherosclerotic coronary arteries: 35.59 +/- 10.34 units/ml (n = 76); 41.88 +/
      8.83 (n = 70) and 43.13 +/- 11.47 (n = 108) in subjects with 1, 2 and 3 affected
      arteries, respectively (r =0.174, P < 0.01). The frequency of CC genotype was
      significantly higher in patients with coronary heart disease (7.48%) than in
      controls (1.62%, P < 0.01), with adjusted odds ratio of 4.367 (95% confidence
      interval: 1.178 to 16.191, P < 0.01), so was the C allele (23.2% vs. 14.9%, P <
      0.05). CONCLUSIONS: High plasma homocysteine thiolactone adducts and the CC 311
      genotype of paraoxonase-2 gene may be the emerging risk factor for coronary heart
      disease.

PMID- 16111669
TI  - Adiponectin serum concentrations in men with coronary artery disease: the
      LUdwigshafen RIsk and Cardiovascular Health (LURIC) study.
AB  - BACKGROUND: Adiponectin, the most abundant adipocytokine of adipose tissue cells,
      has recently been found to be decreased in coronary artery disease (CAD). Data
      concerning adiponectin in different stages of CAD are rare, and it was not
      investigated if adiponectin levels are influenced by the severity of angina
      pectoris. METHODS: Thus, we measured adiponectin serum levels by means of ELISA
      in 1626 male probands, including 273 control subjects, 367 subjects with silent
      CAD, 608 patients with stable, and 378 patients with unstable angina. RESULTS: As
      compared to controls (8.56; 5.85 to 12.85 microg/ml) and subjects with silent CAD
      (8.60; 5.99 to 12.64 microg/ml), adiponectin was significantly decreased in
      patients with stable (7.22; 5.06 to 10.41 microg/ml; p < 0.001 for both) and
      unstable angina (6.72; 4.08 to 10.08 microg/ml; p < 0.001 for both). By a
      logistic regression analysis, low adiponectin levels were identified as a
      significant independent predictor for stable and unstable angina (p < 0.001 for
      both). No significant differences of adiponectin were observed, neither between
      the stable and unstable angina group, nor between any classes of angina according
      to the Canadian Cardiovascular Society (CCS) Angina Score for stable angina.
      CONCLUSIONS: These results suggest, that decreased adiponectin levels are
      indicative for symptomatic CAD, but are not further influenced by the progression
      of this disease.

PMID- 16111670
TI  - Effect of dimethyl sulfoxide on post-thaw viability assessment of CD45+ and CD34+
      cells of umbilical cord blood and mobilized peripheral blood.
AB  - BACKGROUND: The effect of dimethyl sulfoxide (Me2SO) on enumeration of post-thaw
      CD45+ and CD34+ cells of umbilical cord blood (HPC-C) and mobilized peripheral
      blood (HPC-A) has not been systematically studied. METHODS: Cells from
      leukapheresis products from multiple myeloma patients and umbilical cord blood
      cells were suspended in 1, 2, 5, or 10% Me2SO for 20 min at 22 degrees C. Cells
      suspended in Me2SO were then immediately assessed or assessed following removal
      of Me2SO. In other samples, cells were suspended in 10% Me2SO, cooled slowly to 
      60 degrees C, stored at -150 degrees C for 48 h, then thawed. The thawed cells in
      10% Me2SO were diluted to 1, 2, 5, or 10% Me2SO, held for 20 min at 22 degrees C
      and then immediately assessed or assessed after the removal of Me2SO. CD34+ cell
      viability was determined using a single platform flow cytometric absolute CD34+
      cell count technique incorporating 7-AAD. RESULTS: The results indicate that
      after cryopreservation neither recovery of CD34+ cells nor viability of CD45+ and
      CD34+ cells from both post-thaw HPC-A and HPC-C were a function of the
      concentration of Me2SO. Without cryopreservation, when Me2SO is present recovery
      and viability of HPC-C CD34+ cells exposed to 10% Me2SO but not CD45+ cells were
      significantly decreased. Removing Me2SO by centrifugation significantly decreased
      the viability and recovery of CD34+ cells in both HPC-A and HPC-C before and
      after cryopreservation. DISCUSSION: To reflect the actual number of CD45+ cells
      and CD34+ cells infused into a patient, these results indicate that removal of
      Me2SO for assessment of CD34+ cell viability should only be performed if the HPC
      are infused after washing to remove Me2SO.

PMID- 16111671
TI  - Protein kinase C-mediated phosphorylation of the two polybasic regions of
      synaptotagmin VI regulates their function in acrosomal exocytosis.
AB  - We have previously reported that synaptotagmin VI is present in human sperm cells
      and that a recombinant protein containing the C2A and C2B domains abrogates
      acrosomal exocytosis in permeabilized spermatozoa, an effect that was regulated
      by phosphorylation. In this report, we show that each individual C2 domain blocks
      acrosomal exocytosis. The inhibitory effect was completely abrogated by
      phosphorylation of the domains with purified PKCbetaII. We found by site-directed
      mutagenesis that Thr418 and/or Thr419 in the polybasic region (KKKTTIK) of the
      C2B domain--a key region for the function of synaptotagmins--are the PKC target
      that regulates its inhibitory effect on acrosomal exocytosis. Similarly, we
      showed that Thr284 in the polybasic region of C2A (KCKLQTR) is the target for PKC
      mediated phosphorylation in this domain. An antibody that specifically binds to
      the phosphorylated polybasic region of the C2B domain recognized endogenous
      phosphorylated synaptotagmin in the sperm acrosomal region. The antibody was
      inhibitory only at early stages of exocytosis in sperm acrosome reaction assays,
      and the immunolabeling decreased upon sperm stimulation, indicating that the
      protein is dephosphorylated during acrosomal exocytosis. Our results indicate
      that acrosomal exocytosis is regulated through the PKC-mediated phosphorylation
      of conserved threonines in the polybasic regions of synaptotagmin VI.

PMID- 16111672
TI  - Development of the central nervous system in the larvacean Oikopleura dioica and
      the evolution of the chordate brain.
AB  - In non-vertebrate chordates, central nervous system (CNS) development has been
      studied in only two taxa, the Cephalochordata and a single Class (Ascidiacea) of
      the morphologically diverse Urochordata. To understand development and molecular
      regionalization of the brain in a different deeply diverging chordate clade, we
      isolated and determined the expression patterns of orthologs of vertebrate CNS
      markers (otxa, otxb, otxc, pax6, pax2/5/8a, pax2/5/8b, engrailed, and hox1) in
      Oikopleura dioica (Subphylum Urochordata, Class Larvacea). The three Oikopleura
      otx genes are expressed similarly to vertebrate Otx paralogs, demonstrating that
      trans-homologs converged on similar evolutionary outcomes by independent neo- or
      subfunctionalization processes during the evolution of the two taxa. This work
      revealed that the Oikopleura CNS possesses homologs of the vertebrate forebrain,
      hindbrain, and spinal cord, but not the midbrain. Comparing larvacean gene
      expression patterns to published results in ascidians disclosed important
      developmental differences and similarities that suggest mechanisms of development
      likely present in their last common ancestor. In contrast to ascidians, the lack
      of a radical reorganization of the CNS as larvaceans become adults allows us to
      relate embryonic gene expression patterns to three subdivisions of the adult
      anterior brain. Our study of the Oikopleura brain provides new insights into
      chordate CNS evolution: first, the absence of midbrain is a urochordate
      synapomorphy and not a peculiarity of ascidians, perhaps resulting from their
      drastic CNS metamorphosis; second, there is no convincing evidence for a homolog
      of a midbrain-hindbrain boundary (MHB) organizer in urochordates; and third, the
      expression pattern of "MHB-genes" in the urochordate hindbrain suggests that they
      function in the development of specific neurons rather than in an MHB organizer.

PMID- 16111673
TI  - Proadrenomedullin N-terminal peptide and cortistatin activation of MrgX2 receptor
      is based on a common structural motif.
AB  - The G protein-coupled receptor MrgX2 belongs to the large family of the Mas
      related genes or sensory neuron-specific G protein-coupled receptors. The MrgX2
      receptor has been shown to be activated by the peptides cortistatin and
      proadrenomedullin N-terminal peptides (PAMP). Here we investigated the structure
      activity relationship of PAMP and identified key structural features that are
      shared with cortistatin and might explain why two apparently unrelated peptides
      are able to activate a single G protein-coupled receptor.

PMID- 16111674
TI  - Novel parent structures for inhibitors of the murine GABA transporters mGAT3 and
      mGAT4.
AB  - Searching for potent and subtype selective parent structures of the murine gamma
      aminobutyric acid (GABA) transporter subtypes mGAT3 and mGAT4 a series of amino
      acids was characterised in a uniform [3H]GABA uptake test system based on
      transiently expressed mGAT1-4. From several potent inhibitors showing IC50 values
      at mGAT3 and mGAT4 in the low microM range cis-4-aminocrotonic acid and (RS)-2,3
      diaminopropionic acid turned out to be most subtype selective for these
      transporters. With (RS)-isoserine--a compound unknown as GAT inhibitor until now-
      one of the most potent amino acids selectively inhibiting mGAT3 and mGAT4 was
      found. Furthermore, (2-amino-1,3-thiazol-4-yl)acetic acid was identified as the
      first parent structure exhibiting a clear, though still moderate, selective
      inhibition of GABA uptake at mGAT3.

PMID- 16111675
TI  - Huperzine A protects SHSY5Y neuroblastoma cells against oxidative stress damage
      via nerve growth factor production.
AB  - Our previous study demonstrated that huperzine A, a selective
      acetylcholinesterase inhibitor, stimulates the synthesis of nerve growth factor
      (NGF) in cultured rat cortical astrocytes. The present studies are designed to
      examine if huperzine A exerts its neuroprotective activity against oxidative
      stress damage through increasing the synthesis of NGF in SHSY5Y neuroblastoma
      cells. Transient exposure of the cells to 200 microM H2O2 triggered a significant
      reduction of cell viability and decreased the mRNA and protein levels of NGF,
      neurotrophin receptor P75 (P75NTR) receptor and tyrosine kinase A (TrkA)
      receptor. Incubation of cells with 10 microM huperzine A prior to H2O2 exposure
      significantly elevated their survival and restored the mRNA and protein levels of
      NGF, P75NTR receptor and TrkA receptor. These neuroprotective effects of
      huperzine A on H2O2-induced cytotoxicity were blocked by the TrkA receptor
      phosphorylation inhibitor K252alpha, and were antagonized by the mitogen
      activated protein (MAP)/extracellular signal-regulated kinase (ERK) inhibitor,
      PD98059. The present results indicate that the cytoprotective effect of huperzine
      A is mediated at least partly by up-regulated NGF and NGF receptors. The results
      also show that the MAP/ERK kinase signal pathway is crucial for huperzine A to
      protect against H2O2-induced damage in SHSY5Y cells.

PMID- 16111676
TI  - The effect of N-acetylcysteine on cardiac contractility to dobutamine in rats
      with streptozotocin-induced diabetes.
AB  - We examined if myocardial depression at the acute phase of diabetes (3 weeks
      after injection of streptozotocin, 60 mg/kg i.v.) is due to activation of
      inducible nitric oxide synthase and production of peroxynitrite, and if treatment
      with N-acetylcysteine (1.2 g/day/kg for 3 weeks, antioxidant) improves cardiac
      function. Four groups of rats were used: control, N-acetylcysteine-treated
      control, diabetic and N-acetylcysteine-treated diabetic. Pentobarbital
      anaesthetized diabetic rats, relative to the controls, had reduced left
      ventricular contractility to dobutamine (1-57 microg/min/kg). The diabetic rats
      also had increased myocardial levels of thiobarbituric acid reactive substances,
      immunostaining of inducible nitric oxide synthase and nitrotyrosine, and similar
      baseline 15-F2t-isoprostane. N-acetylcysteine did not affect responses in the
      control rats; but increased cardiac contractility to dobutamine, reduced
      myocardial immunostaining of inducible nitric oxide synthase and nitrotyrosine
      and level of 15-F2t-isoprostane, and increased cardiac contractility to
      dobutamine in the diabetic rats. Antioxidant supplementation in diabetes reduces
      oxidative stress and improves cardiac function.

PMID- 16111677
TI  - Chronic effects of AJ-9677 on energy expenditure and energy source utilization in
      rats.
AB  - The effects of AJ-9677 on metabolic parameters were examined in rats that had or
      had not been chronically treated with this beta3-adrenoceptor agonist. A
      challenge administration of AJ-9677 increased both the temperature of brown
      adipose tissue and energy expenditure in both groups of rats. However, whereas
      the former effect was subject to desensitization, the latter effect was augmented
      by prior chronic administration of AJ-9677. Whereas a challenge administration of
      AJ-9677 induced a decrease in the respiratory quotient that persisted for at
      least 15 h in rats pretreated with vehicle, the initial decrease in this
      parameter lasted for only 4 h in rats pretreated with AJ-9677. These results
      suggest that, in rats subjected to chronic treatment with AJ-9677, a challenge
      administration of this drug increased energy expenditure by stimulation not only
      of fat oxidation but also of glucose oxidation.

PMID- 16111678
TI  - Peripheral participation of the phosphodiesterase 3 on formalin-evoked
      nociception.
AB  - The local peripheral (subcutaneous) injection of phosphodiesterase 3 inhibitor
      trequinsin dose-dependently enhanced formalin-evoked flinching during late second
      phase of this test. Treatment with the nitric oxide synthase inhibitor N-L-nitro
      arginine methyl ester or guanylyl cyclase inhibitor 1-H-[1,2,4,]oxadiazolo[4,3
      a]quinoxalin-1-one significantly reversed trequinsin-induced pronociceptive
      effect. Results suggest that the peripheral phosphodiesterase 3 may play an
      important physiologic role on inflammatory pain by controlling cyclic AMP levels
      and therefore the nociceptor threshold.

PMID- 16111679
TI  - MicroRNA function in animal development.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally
      regulate gene expression by base-pairing to mRNAs. Hundreds of miRNAs have been
      identified in various multicellular organisms and many miRNAs are evolutionarily
      conserved. Although the biological functions of most miRNAs are unknown, miRNAs
      are predicted to regulate up to 30% of the genes within the human genome.
      Gradually, we are beginning to understand the functions of individual miRNAs and
      the general function of miRNA action. Here, we review the recent advances in
      miRNA biology in animals. Particularly, we focus on the roles of miRNAs in
      vertebrate development and disease.

PMID- 16111680
TI  - Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by
      Th1 and Th2 cytokines in respiratory tract epithelium.
AB  - Partially reduced metabolites of molecular oxygen, superoxide (O2-) and hydrogen
      peroxide (H2O2), are detected in respiratory tract lining fluid, and it is
      assumed that these are key components of innate immunity. Whether these reactive
      oxygen species (ROS) are produced specifically by the respiratory epithelium in
      response to infection, or are a non-specific by-product of oxidant-producing
      inflammatory cells is not well characterized. Increasing evidence supports the
      hypothesis that the dual function NAD(P)H oxidases/peroxidases, Duox1 and Duox2,
      are important sources of regulated H2O2 production in respiratory tract
      epithelium. However, no studies to date have characterized the regulation of Duox
      gene expression. Accordingly, we examined Duox1 and Duox2 mRNA expression by real
      time PCR in primary respiratory tract epithelial cultures after treatment with
      multiple cytokines. Herein, we determined that Duox1 expression was increased
      several-fold by treatment with the Th2 cytokines IL-4 and IL-13, whereas Duox2
      expression was highly induced following treatment with the Th1 cytokine IFN
      gamma. Duox2 expression was also elevated by polyinosine-polycytidylic acid
      (poly(I:C)) and rhinovirus infection. Diphenyleneiodonium (DPI)-inhibitable
      apical H2O2 production was similarly increased by the addition of Th1 or Th2
      cytokines. These results demonstrate for the first time the regulation of Duox
      expression by immunomodulatory Th1 and Th2 cytokines, and suggest a mechanism by
      which ROS production can be regulated in the respiratory tract as part of the
      host defense response.

PMID- 16111681
TI  - Characterization of acetohydroxyacid synthase from Mycobacterium tuberculosis and
      the identification of its new inhibitor from the screening of a chemical library.
AB  - Acetohydroxyacid synthase (AHAS) is a thiamin diphosphate- (ThDP-) and FAD
      dependent enzyme that catalyzes the first common step in the biosynthetic pathway
      of the branched-amino acids such as leucine, isoleucine, and valine. The genes of
      AHAS from Mycobacterium tuberculosis were cloned, and overexpressed in E. coli
      and purified to homogeneity. The purified AHAS from M. tuberculosis is
      effectively inhibited by pyrazosulfuron ethyl (PSE), an inhibitor of plant AHAS
      enzyme, with the IC(50) (inhibitory concentration 50%) of 0.87 microM. The
      kinetic parameters of M. tuberculosis AHAS were determined, and an enzyme
      activity assay system using 96-well microplate was designed. After screening of a
      chemical library composed of 5600 compounds using the assay system, a new class
      of AHAS inhibitor was identified with the IC(50) in the range of 1.8-2.6 microM.
      One of the identified compounds (KHG20612) further showed growth inhibition
      activity against various strains of M. tuberculosis. The correlation of the
      inhibitory activity of the identified compound against AHAS to the cell growth
      inhibition activity suggested that AHAS might be served as a target protein for
      the development of novel anti-tuberculosis therapeutics.

PMID- 16111682
TI  - Proteasome comprising a beta1 inducible subunit acts as a negative regulator of
      NADPH oxidase during elicitation of plant defense reactions.
AB  - Elicitation of defense reactions in tobacco by cryptogein, triggered a production
      of active oxygen species (AOS) via the NADPH oxidase, NtrbohD, and an
      accumulation of beta1din, a defense induced beta-type subunit of 20S proteasome.
      The proteasome inhibitor, MG132, stimulated this AOS production. Tobacco cells
      transformed with sense constructs of beta1din showed an inhibition of the AOS
      production following elicitin treatment, whereas the antisense transformed cells
      showed a strongly enhanced AOS production. In cells transformed with sense
      construct of beta1din, the NtrbohD transcripts failed to be induced by cryptogein
      as observed in control and antisense transformed cells. Conversely, in tobacco
      cells transformed with antisense constructs for NtrbohD, beta1din transcripts
      remained at a low level after elicitation. These results constitute the first
      demonstration of proteasome comprising beta1din acting as a negative regulator of
      NtrbohD and contributes to the regulation of AOS generation during plant defense
      reactions.

PMID- 16111683
TI  - Free uptake of cell-penetrating peptides by fission yeast.
AB  - An increasing number of peptides translocate the plasma membrane of mammalian
      cells promising new avenues for drug delivery. However, only a few examples are
      known to penetrate the fungal cell wall. We compared the capacity of different
      fluorophore-labelled peptides to translocate into fission yeast and human cells
      and determined their intracellular distribution. Most of the 20 peptides tested
      were able to enter human cells, but only one, transportan 10 (TP10), efficiently
      penetrated fission yeast and was distributed uniformly inside the cells. The
      results show that the fungal cell wall may reduce, but does not block peptide
      uptake.

PMID- 16111684
TI  - HAUSP, a deubiquitinating enzyme for p53, is polyubiquitinated, polyneddylated,
      and dimerized.
AB  - The tumor suppressor protein p53 is ubiquitinated and neddylated by MDM2 and then
      degraded by 26S proteasome. However, p53 is stabilized by the HAUSP (Herpes-virus
      associated ubiquitin-specific protease) deubiquitinating enzyme. In this study,
      we discovered that rat HAUSP (rHAUSP) is polyubiquitinated, polyneddylated, and
      dimerized using co-immunoprecipitation assays. This suggests that rHAUSP may
      function as a dimer or multimer and is also degraded through the proteasome
      mediated degradation. Transfection of rHAUSP into RGC-Lac-Z cell line with the
      integrated p53 response element revealed that rHAUSP contributed to p53
      stabilization, and a rHAUSP (C224S) mutant contributed to p53 destabilization in
      a dose-dependent manner.

PMID- 16111685
TI  - Estradiol fatty acid esterification is increased in high density lipoprotein
      subclass 3 isolated from hypertriglyceridemic subjects.
AB  - Estrogen fatty acid esters are potent lipophilic estrogens transported
      exclusively in lipoproteins. They are formed in HDL in a reaction catalyzed by
      LCAT which is considered a prerequisite for their antioxidative action. Our
      previous studies in normotriglyceridemic (NTG) individuals demonstrated that
      estradiol (E2) esterification occurred mainly in HDL3 causing accumulation of
      esterified, but not of unesterified E2 in the lipoprotein particles. Using HDL
      obtained from hypertriglyceridemic (HTG) patients, we now investigated the effect
      of altered HDL composition on E2 esterification. Ultracentrifugally isolated HDL2
      and HDL3 from NTG- and HTG-males were incubated in an in vitro model system with
      radioactive and with supraphysiological concentrations of non-radioactive E2 with
      and without exogenous LCAT. After purification, copper-induced oxidation of HDL
      was measured by monitoring conjugated diene formation. The results demonstrated
      that (i) E2 esterification occurring mainly in HDL3 was significantly more
      efficient in HTG-HDL3 compared to NTG-HDL3, (ii) triglyceride content in HDL3
      correlated positively with E2 esterification rate, and (iii) addition of both
      exogenous LCAT and E2 into the incubation prolonged lag time of HDL3 oxidation.
      Thus, HDL composition regulates LCAT-facilitated E2 esterification but the in
      vivo role of this finding can be verified only in experiments using physiological
      hormone concentrations.

PMID- 16111686
TI  - Multiphase hemodynamic simulation of pulsatile flow in a coronary artery.
AB  - A multiphase transient non-Newtonian three-dimensional (3-D) computational fluid
      dynamics (CFD) simulation has been performed for pulsatile hemodynamics in an
      idealized curved section of a human coronary artery. We present the first
      prediction, to the authors' knowledge, of particulate buildup on the inside
      curvature using the multiphase theory of dense suspension hemodynamics. In this
      study, the particulates are red blood cells (RBCs). The location of RBC buildup
      on the inside curvature correlates with lower wall shear stress (WSS) relative to
      the outside curvature. These predictions provide insight into how blood-borne
      particulates interact with artery walls and hence, have relevance for
      understanding atherogenesis since clinical observations show that atherosclerotic
      plaques generally form on the inside curvatures of arteries. The buildup of RBCs
      on the inside curvature is driven by the secondary flow and higher residence
      times. The higher viscosity in the central portion of the curved vessel tends to
      block their flow, causing them to migrate preferentially through the boundary
      layer. The reason for this is the nearly neutrally buoyant nature of the dense
      two-phase hemodynamic flow. The two-phase non-Newtonian viscosity model predicts
      greater shear thinning than the single-phase non-Newtonian model. Consequently,
      the secondary flow induced in the curvature is weaker. The waveforms for computed
      hemodynamic parameters, such as hematocrit, WSS, and viscosity, follow the
      prescribed inlet velocity waveforms. The lower oscillatory WSS produced on the
      inside curvature has implications for understanding thickening of the intimal
      layer.

PMID- 16111687
TI  - Lines of dense nanoparticle colloidal suspensions evaporating on a flat surface:
      formation of non-uniform dried deposits.
AB  - Line evaporation of dense nanoparticle suspensions is studied theoretically and
      experimentally. The 2-D lines are drawn by a pen-like nozzle continuously
      dispensing a commercially available concentrated organic suspension (50 wt%; 4.3
      vol%) of 5 nm gold nanoparticles in toluene solvent. Such particle-containing
      lines show promise for industrial applications where circuits are inkjet-printed
      and heat-treated to dry off the organic solvent and sinter the nanoparticles,
      thus producing a continuous electrically conducting path. The employed
      nanosuspension displays spontaneous thickening upon contact with a solid surface
      in the ambient atmosphere, and thus does not dry according to the well
      established coffee-stain forming mechanism applicable to dilute particle
      suspensions. In the present work, model lines ( approximately 1 mm width) are
      studied to elucidate the drying peculiarities of such nanoparticle slurries.
      These scaled-up lines allow detailed spatial measurements of their topography
      throughout their prolonged evaporation period, and make possible direct
      comparisons between experiment and theory. The results show the particle deposits
      formed by evaporative drying of these lines to be of non-uniform thickness with a
      dent in the middle of the lateral cross-section. Formation of this practically
      undesirable landscape is attributed to the highly non-uniform evaporative
      character of sessile or pendent liquid lines, which results in a non-uniform
      consolidation of the porous phase formed upon contact with the solid surface. The
      formulated description of the shape changing process, as done in the framework of
      the consolidation theory, yields predicted deposit speck shapes that compare
      favorably with the temporally resolved experimental data.

PMID- 16111688
TI  - Quasi-static liquid-air drainage in narrow channels with variations in the gap.
AB  - This paper studies the shape of an air bubble quasi-statically flowing in the
      longitudinal direction of narrow channels. Two bottom topographies are treated,
      i.e., linear and quadratic variations of the gap along the transverse direction.
      This work analyses the main characteristics of the gas-liquid interface with
      respect to the wedge aspect ratio. From the convergence of asymptotic, numerical
      and experimental analyses, we found simple dependences for the finger width and
      total curvature as a function of channel aspect ratio. These results provide
      simple and general expressions for the pressure drop needed to overcome capillary
      forces and push the air finger inside the channel.

PMID- 16111689
TI  - Surface modification of mechanochemically activated kaolinites by selective
      leaching.
AB  - Low- and high-defect kaolinites mechanochemically activated for different periods
      of time have been treated with sulfuric acid solution. These modified materials
      were analyzed using a combination of X-ray diffraction, thermogravimetry,
      chemical analysis, diffuse reflectance Fourier transform infrared spectroscopy,
      as well as specific surface area and pore size distribution measurements. In
      addition to the mechanochemically amorphized part, the disordered and the
      adequately distorted phases also reacted with sulfuric acid. The specific surface
      areas of the leached samples of the partially or the completely amorphized
      materials were found to be greater than those of the thermally amorphized ones.
      The acid treatment results in a greater total pore volume for the partially
      amorphized materials than for the totally amorphized mineral. The partially
      amorphized high-defect kaolinite was proved to be more soluble than the low
      defect kaolinite under similar conditions.

PMID- 16111690
TI  - Preparation of highly porous carbon from fir wood by KOH etching and CO2
      gasification for adsorption of dyes and phenols from water.
AB  - Fir wood was first carbonized for 1.5 h at 450 degrees C, then soaked in a KOH
      solution KOH/char ratio of 1, and last activated for 1 h at 780 degrees C. During
      the last hour CO2 was poured in for further activation for 0, 15, 30, and 60 min,
      respectively. Carbonaceous adsorbents with controllable surface area and pore
      structure were chemically activated from carbonized fir wood (i.e., char) by KOH
      etching and CO2 gasification. The pore properties, including the BET surface
      area, pore volume, pore size distribution, and pore diameter, of these activated
      carbons were first characterized by the t-plot method based on N2 adsorption
      isotherms. Fir-wood carbon activated with CO2 gasification from 0 to 60 min
      exhibited a BET surface area ranging from 1371 to 2821 m2 g(-1), with a pore
      volume significantly increased from 0.81 to 1.73 m2 g(-1). Scanning electron
      microscopic (SEM) results showed that the surfaces of honeycombed holes in these
      carbons were significantly different from those of carbons without CO2
      gasification. The adsorption of methylene blue, basic brown 1, acid blue 74, p
      nitrophenol, p-chlorophenol, p-cresol, and phenol from water on all the carbons
      studied was examined to check their chemical characteristics. Adsorption kinetics
      was in agreement with the Elovich equation, and all equilibrium isotherms were in
      agreement with the Langmuir equation. These results were used to compare the
      Elovich parameter (1/b) and the adsorption quantity of the unit area (q(mon)/Sp)
      of activated carbons with different CO2 gasification durations. This work
      facilitated the preparation of activated carbon by effectively controlling pore
      structures and the adsorption performance of the activated carbon on adsorbates
      of different molecular forms.

PMID- 16111691
TI  - Size tunable synthesis of cysteine-capped CdS nanoparticles by gamma-irradiation.
AB  - Highly water soluble and biocompatible L-cysteine-capped CdS nanoparticles having
      narrow size distribution were synthesized for the first time by gamma-irradiation
      technique without using any additional stabilizer. FTIR study shows that CdS
      nanoparticles are capped through mercapto-group of cysteine amino acid while its
      free amino and carboxylate groups make it amenable to bio-conjugation. Size and
      luminescence of the nanoparticles can be well controlled by varying the
      parameters like radiation dose, pH and concentration of cysteine. The observed
      results suggest that pH 7 can be optimum for the synthesis of L-cysteine-capped
      CdS nanoparticles. CdS nanoparticles synthesized with molar ratio of
      Cd(2+):cysteine, 1:60 at pH 7 were found to be most luminescent. All
      nanoparticles formed lie in the size quantization regime and exhibit good
      crystallinity. Remarkable improvement in stability and luminescence was achieved
      on changing pH of as-prepared nanoparticles from 7 to 11.

PMID- 16111692
TI  - Sorption of Sr(II) and Eu(III) onto pyrite under different redox potential
      conditions.
AB  - Understanding sorption processes is fundamental for the prediction of
      radionuclide migration in the surroundings of a deep geological disposal of high
      level nuclear wastes. Pyrite (FeS2) is a mineral phase often present as
      inclusions in temperate soils. Moreover, it constitutes an indirect corrosion
      product of steel, a containment material that is candidate to confine
      radionuclides in deep geological disposals. The present study was thus initiated
      to determine the capacity of pyrite to immobilize Sr(II) and Eu(III). An air
      oxidized pyrite and a freshly acid-washed (non-oxidized) pyrite were used in
      background electrolytes of varying reducing-oxidizing ability (NaCl, NH3OHCl, and
      NaClO4) to study the sorption of both cationic species. The sorptive capacity of
      pyrite appeared directly correlated to the oxidation of the surface. Non-oxidized
      pyrite had nearly no affinity for the studied cations whereas Sr(II) and Eu(III)
      species were significantly retained by oxidized pyrite surface. Using the surface
      complexation theory, sorption mechanisms were modeled with the Fiteql v3.2 and
      the Jchess 2.0 codes. Sorption of both Sr and Eu was well fitted, assuming
      hydroxylated species as the major surface species. This study demonstrates that
      not only the components of a barrier but also the redox conditions and
      specifications should be well characterized to predict transport of contaminants
      in the surrounding of a nuclear wastes disposal.

PMID- 16111693
TI  - Surface properties of mixtures of surface-active sugar derivatives with ionic
      surfactants: theoretical and experimental investigations.
AB  - Surface properties of systems that are mixtures of ionic surfactants and sugar
      derivatives-anionic surfactant sodium dodecyl sulfate and n-dodecyl-beta-D
      maltoside (SDS/DM) and cationic surfactant dodecyltrimethylammonium bromide and n
      dodecyl-beta-D-glucoside (DTABr/DG)-were investigated. The experimental results
      obtained from measurements of surface tension of mixtures with various ratio of
      ionic to nonionic components were analyzed by two independent theories. First is
      Motomura theory, derived from the Gibbs-Duhem equation, allowing for indirect
      evaluation of the composition of mixed monolayers and the Gibbs energies of
      adsorption, corresponding to mutual interaction between surfactants in mixed
      adsorbed film. As second theory we used our newly developed theoretical model of
      adsorption of ionic-nonionic surfactant mixtures. Using this approach, we were
      able to describe the experimental surface tension isotherms for mixtures of
      surface-active sugar derivatives and ionic surfactants. We obtained a good
      agreement with experimental data using the same set of model parameters for a
      whole range of studied compositions of a given surfactant mixture. The values of
      surface excess calculated from both theories agreed with each other with a
      reasonable accuracy. However, the newly developed model of adsorption of ionic
      nonionic surfactant mixtures has the advantage of straightforward determination
      of surface layer composition. By the solution of equations of adsorption, one can
      obtain directly the values of surface excess of all components (surfactant ions,
      counterions, and nonionic surfactants molecules), which are present in the
      investigated system.

PMID- 16111694
TI  - Color properties of gold-silver alternate nanowires electrochemically grown in
      the pores of aluminum anodic oxidation film.
AB  - Repeated electrodeposition of gold and silver on anodized aluminum plate yielded
      Au-Ag alternate nanowires in the geometrically anisotropic pores of the anodic
      oxidation films with mean diameter 10 nm and depth 10 mum, respectively. The
      absorption maximum wavelengths in the visible region resulting from the
      transverse surface plasmon resonances of Au and Ag nanorods are invariant with
      their growth. Consequently, the color of the anodized aluminum was simply tuned
      in a wide range, which is impossible to attain in each monometallic system.

PMID- 16111695
TI  - ATR-FTIR investigation on the complexation of myo-inositol hexaphosphate with
      aluminum hydroxide.
AB  - The adsorption isotherm of and the pH effect on the adsorption of myo-inositol
      hexaphosphate (myo-IP6) on amorphous aluminum hydroxide was investigated. It was
      found that the adsorption isotherm of myo-IP6 on aluminum hydroxide could be well
      fitted with the Freundlich isotherm. The amount of myo-IP6 adsorbed remained
      almost constant in the range of pH 4.0 to 7.0, but it decreased considerably as
      the initial pH was over 7. The adsorption of myo-IP6 resulted in an increase in
      the pH level due to the release of OH(-) ions, which suggested that the
      adsorption of myo-IP6 on aluminum hydroxide was caused by a ligand exchange
      reaction. ATR-FTIR analysis of myo-IP6 in solution and adsorbed on aluminum
      hydroxide at different pH were performed. The ATR-FTIR investigation indicated
      that myo-IP6 was adsorbed onto aluminum hydroxide by forming inner-sphere
      complexes and adsorption facilitated the deprotonation of phosphate groups. The
      asymmetric vibration of the PO bond in AlPO(-)(3) appearing at a lower frequency
      than that in the terminal HPO(-)(3) indicated that Al bound to the O atom not as
      strongly as the H atom did. The ATR-FTIR investigation and theoretical
      calculation (with the Gaussian 03 program) revealed that three of the six
      phosphate groups in myo-IP6 molecules were bound to aluminum hydroxide while the
      other three remained free when myo-IP6 was adsorbed on aluminum hydroxide.

PMID- 16111696
TI  - Children's suggestibility for an instance of a repeated event versus a unique
      event: the effect of degree of association between variable details.
AB  - Are children who experience an event repeatedly more suggestible about an
      instance of the event than children who experience it once? Researchers have
      answered this question both in the affirmative and in the negative. In this
      study, we hypothesized that the degree of association between details that
      changed across instantiations of the event would help to explain the discrepancy.
      Preschoolers (4- and 5-year-olds) and first graders (6- and 7-year-olds)
      participated in either a single play session or four repeated play sessions, each
      of which contained 16 critical details. Across play sessions in the repeat-event
      condition, half of the critical details were associated and half were not
      associated. During a biasing interview 2 weeks later, children were misinformed
      about half of the critical details. The next day, children answered free and cued
      recall questions about the target play session. Among older children, repeat
      event participants were more suggestible than single-event participants,
      especially for high-association details. Among younger children, repeat-event
      participants were more suggestible than single-event participants for low
      association details. Consistent with some current theories of children's memory,
      older children were more suggestible than younger children.

PMID- 16111697
TI  - Detection of two functional polymorphisms in the promoter region of the IL-18
      gene by single-tube allele specific PCR and melting temperature analysis.
AB  - IL-18 is an important cytokine in both innate and acquired immunity. IL-18
      promoter polymorphisms have been investigated in several autoimmune and
      infectious diseases. Here we present two assays for a medium to a high throughput
      genotyping of C-607A and G-137C IL-18 SNPs. Using these protocols we have been
      able to rapidly genotype a cohort of 131 healthy Italian individuals. The assays,
      based on a multiplex allele-specific PCR and the melting temperature analysis of
      the PCR product, are rapid, easily automated, inexpensive and well suited to case
      control association studies.

PMID- 16111698
TI  - Evaluation of the concept of heterology in a monoclonal antibody-based ELISA
      utilizing direct hapten linkage to polystyrene microtiter plates.
AB  - A series of new heterologous haptens has been synthesized and used as coating
      haptens in an antigen-immobilized immunoassay with a monoclonal antibody against
      atrazine. Coating was achieved by covalently linking the different haptens to a
      glutaraldehyde network directly bound to the polystyrene surface of a standard 96
      well microtiter plate. With the assay designed in the antigen-immobilized format
      with direct chemical linkage of the hapten to the solid polystyrene surface well
      defined hapten densities were achieved in all experiments. The results of
      different experiments with different coating haptens were comparable. Using
      different heterologous haptens it appears that the concept of heterology is
      applicable in this case and can be used to enhance the sensitivity of an
      immunoassay in the coating-hapten format.

PMID- 16111699
TI  - Development and evaluation of three real-time immuno-PCR assemblages for
      quantification of PSA.
AB  - Real-time PCR is a very sensitive technique to measure DNA concentrations. In
      real-time immuno-PCR, it is used as the detection system for quantification of
      proteins. Many ways to perform and assemble real-time immuno-PCR are possible. We
      have tested three different approaches for the detection of prostate specific
      antigen (PSA) and compared them with each other and with ELISA. We also
      demonstrate the applicability of real-time immuno-PCR to classify clinical PSA
      samples. Assemblage I is performed stepwise attaching the capture antibody to the
      vessel surface by adsorption and having the DNA-label linked to the detection
      antibody through biotin and streptavidin. In assemblage II, capture antibody is
      also adsorbed to the vessel surface but the detection antibody is pre-conjugated
      to the DNA-label. Assemblage III uses the pre-conjugated detection antibody/DNA
      label but binds the capture antibody through biotin to surface immobilized
      streptavidin. We found assemblage II to be the most sensitive, with a detection
      limit of 4.8 x 10(5) PSA molecules. This can be compared to the detection limit
      of the ELISA, which is 5.7 x 10(7) molecules. Assemblage III was the most
      reproducible with a standard deviation (SD) of 0.21 cycles, while assemblage I
      was the least reproducible (SD=0.45 cycles). The SD of assemblage II was 0.25
      cycles. We conclude that using pre-conjugated detection antibody/DNA-label
      enhances both the sensitivity and the reproducibility of real-time immuno-PCR.
      Measurements of PSA in serum samples using real-time immuno-PCR correlated well
      with measurements performed with ELISA. The real-time immuno-PCR measurements
      were more sensitive and the dynamic range was larger than with the ELISA.

PMID- 16111700
TI  - Altered fibroblast function following myocardial infarction.
AB  - Adequate wound healing and scar formation is an essential response to myocardial
      infarction (MI), and fibroblasts are primary cellular components regulating the
      process. How fibroblast functions are altered post-MI and to what extent these
      abnormalities persist in vitro is not well understood. Accordingly, we isolated
      myocardial fibroblasts from MI and non-MI (remote) regions at 7 days post-MI
      (n=35) and from the free wall and septum of unoperated control C57BL/6 mice
      (n=14). Proliferation was increased 182+/-28% in MI, but not in remote,
      fibroblasts compared with unoperated controls (P=0.01). Migration decreased 61+/
      8%, adhesion to laminin decreased 79+/-8%, adhesion to collagen IV increased
      196+/-27%, and collagen synthesis increased 169+/-24% in fibroblasts isolated
      from the MI region (all P<0.05). Migration, adhesion, and collagen synthesis
      changes were similar in remote fibroblasts, and the phenotypic differences were
      maintained through passage four. Transforming growth factor beta1 (TGFbeta1) is a
      bioactive molecule that has been shown to affect fibroblast function. Stimulation
      of unoperated control fibroblasts with 10 ng/ml TGFbeta(1) increased
      proliferation 137+/-7% (P=0.03 vs. unstimulated), increased adhesion to collagen
      IV 149+/-6% (P<0.01), and increased collagen I levels 187+/-10% (P=0.01).
      TGFbeta1 may, therefore, explain some of the changes in post-MI fibroblast
      phenotype. These data demonstrate for the first time region specific alterations
      in post-MI fibroblast biology that are maintained in vitro. Additionally, our
      model provides a novel in vitro template for examining the cellular mechanisms of
      wound healing and scar formation post-MI.

PMID- 16111701
TI  - Pol III proofreading activity prevents lesion bypass as evidenced by its
      molecular signature within E.coli cells.
AB  - Replication of genomes that contain blocking DNA lesions entails the transient
      replacement of the replicative DNA polymerase (Pol) by a polymerase specialized
      in lesion bypass. Here, we isolate and visualize at nucleotide resolution level,
      replication intermediates formed during lesion bypass of a single N-2
      acetylaminofluorene-guanine adduct (G-AAF) in vivo. In a wild-type strain, a
      ladder of replication intermediates mapping from one to four nucleotides upstream
      of the lesion site, can be observed. In proofreading-deficient strains (mutD5 or
      dnaQ49), these replication intermediates disappear, thus assigning the
      degradation ladder to the polymerase-associated exonuclease activity. Moreover,
      in mutD5, a new band corresponding to the insertion of a nucleotide opposite to
      the lesion site is observed, suggesting that the polymerase and exonuclease
      activities of native Pol III enter a futile insertion-excision cycle that
      prevents translesion synthesis. The bypass of the G-AAF adduct located within the
      NarI sequence context requires the induction of the SOS response and involves
      either Pol V or Pol II in an error-free or a frameshift pathway, respectively. In
      the frameshift mutation pathway, inactivation of the proofreading activity
      obviates the need for SOS induction but nonetheless necessitates a functional
      polB gene, suggesting that, although proofreading-deficient Pol III incorporates
      a nucleotide opposite G-AAF, further extension still requires Pol II. These data
      are corroborated using a colony-based bypass assay.

PMID- 16111702
TI  - Candida albicans: the estrogen target for vaginal colonization.
AB  - BACKGROUND: Estradiol (E(2)) stimulates colonization of the vagina by Candida
      albicans. Although this yeast expresses an estrogen-binding protein (EBP), the
      cellular target for estrogenic modulation of this infection is unresolved.
      Findings support direct E(2)-induced C. albicans growth as well as indirect
      effects via E(2)-induced changes in the vaginal epithelium. Our primary goal was
      to pursue the issue of direct versus indirect estrogen action on vaginal
      candidiasis using diethylstilbestrol (DES), an efficacious mammalian estrogen
      receptor agonist, which exhibits no detectable affinity for the EBP of C.
      albicans. METHODS: We used both in vitro and in vivo experimentation with an EBP
      positive strain of C. albicans isolated from the human vagina. Ligand-binding
      studies were performed with steroidal and nonsteroidal estrogens and anti
      estrogens using the soluble EBP from both the yeast and the rat uterus. Mature
      ovariectomized rats were treated with either E(2) or DES for 7 days before and
      after C. albicans inoculation into the vaginas. Subsequent estrogen-sensitive
      colonization was quantified based on cultures of vaginal homogenates on Sabouraud
      dextrose (SD) agar pour plates. RESULTS: We confirmed that our isolate of C.
      albicans contained a high-affinity EBP, with no detectable affinity for DES.
      Vaginal colonization by C. albicans was 8.6-fold greater in response to in vivo
      treatment with E(2) than with the comparable dose regimen of DES. CONCLUSIONS:
      The mechanism for estrogen-sensitive vaginal colonization by C. albicans includes
      a functional ligand-EBP interaction within the yeast.

PMID- 16111703
TI  - CADASIL with NOTCH3 S180C presenting anticipation of onset age and
      hallucinations.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an inherited disease leading to strokes and
      vascular dementia. The average age of onset for stroke is 45 years with a range
      of about 30 to 70 years. We describe a Japanese CADASIL family showing S180C in
      the exon 4 of NOTCH3, presenting an anticipation of the onset age for stroke. MRI
      demonstrated a similar extent of white matter involvement in younger and older
      individuals, supporting the presence of anticipation. In addition, hallucinations
      in 71% of affected patients, and delusions in 57% were also described. Our
      findings in this family suggest that a specific NOTCH3 mutation was related to
      unique clinical features, although such correlations have seldom been encountered
      in CADASIL.

PMID- 16111704
TI  - Bilateral common carotid artery occlusion--a case report and literature review.
AB  - Although unilateral common carotid artery (CCA) occlusion and bilateral internal
      carotid artery (ICA) occlusion have been reported in the past, bilateral CCA
      occlusion is rare. The management and mechanism of unilateral CCA occlusion and
      bilateral ICA occlusion are debatable, but those of bilateral CCA occlusion are
      largely unknown. Herein, we present a case of bilateral CCA occlusion that had an
      acceptable outcome with medical treatment. The literature regarding unilateral
      CCA occlusion, bilateral ICA occlusion and bilateral CCA occlusion is also
      discussed. Experience implies that the collateral circulation gives rise to the
      clinical presentation, and may affect the outcome of various managements. Our
      review and case study may provide new information for future studies of carotid
      artery occlusion.

PMID- 16111705
TI  - A test for the evaluation of the lateral cutaneous branch of the iliohypogastric
      nerve using somatosensory evoked potentials.
AB  - Iliohypogastric nerve (IHN) lesions are rare and usually due to abdominal surgery
      or trauma. There is no established electrophysiologic test for evaluating this
      nerve. A method is proposed to evaluate the IHN lateral cutaneous branch using
      somatosensory evoked potentials (SSEP). SSEP were elicited in 20 subjects using
      electrical stimulation from the greater trochanter up to 7 cm posterior to a
      point on the posterior axillary line, at the level of the greater trochanter. The
      active recording electrodes were placed 2 cm behind the Cz electrode in the
      midline, and the reference electrode midway between the Fpz and Fz electrodes in
      the midline. Stable responses were elicited in 19/20 subjects (12 male), aged 19
      52 years (mean 32+/-6.6). Average positive peak onset latency was 32.5+/-3.7
      msec, average amplitude 0.96+/-0.4 microV. Side-to-side latency difference range
      was 0-3.7 msec and amplitude difference range 0.06-1.04 microV. The technique
      proved sensitive in two cases with IHN injury following trauma, a 24-year-old
      male with a large hematoma over the right hip from the iliac crest to the greater
      trochanter tested twice one year apart, with stable repeat responses, and a 26
      year-old female who sustained a crush injury to the right lateral pelvis. A side
      to-side latency difference >3.7 msec or a unilateral absent response should be
      regarded as abnormal. This test may be useful for confirming the clinical picture
      of IHN lateral cutaneous branch lesions.

PMID- 16111706
TI  - Focal seizures after treatment with fluvastatin in a patient with a history of
      catastrophic antiphospholipid syndrome.
AB  - We report a 36-year-old woman with the occurrence of painful focal seizures of
      her left hand and the left leg. She also had focal motor seizures at the left
      corner of her mouth. The duration and frequency of the episodes increased over
      four days from a few seconds once a day to frequent intervals lasting more than
      four hours at a time. The symptoms appeared one day after start of the treatment
      with fluvastatin (40 mg) administered in order to diminish the endothelial
      activation induced by antiphospholipid antibodies (aPL). The patient suffered
      from severe manifestations of the antiphospholipid syndrome (APS) including
      Catastrophic Antiphospholipid Syndrome (CAPS, Asherson's syndrome). In this case
      a single 40 mg dose of oral fluvastatin was linked to seizures. After
      discontinuation of this treatment, the seizures immediately disappeared and the
      patient fully recovered without evidence of permanent neurological damage. This
      data links statins to seizures in patients with compromised blood brain barrier
      such as APS.

PMID- 16111707
TI  - Consensus recommendations of the Italian Association for Neuroimmunology for
      immunochemical cerebrospinal fluid examination.
AB  - In 2002-2003, the Italian Association for Neuroimmunology (AINI) ran a program
      for procedure and method standardization in neuroimmunology. The main purposes of
      the program were: a) to improve the overall quality of analytical performance
      and, simultaneously, to reduce costs by resource optimization; b) to establish
      the bases for clinical guidelines in neurology; c) to promote the formation of
      laboratory networks and of joint research projects; d) to facilitate the
      procedures for certification required by governmental/non-governmental agencies.
      This report summarizes the consensus recommendations of a panel of AINI
      neuroimmunologists/biochemists involved in the field of cerebrospinal fluid
      examination. The collection process for said recommendations was guided by
      "impact-factored" literature and the knowledge of the experts involved.
      Communication was by email and face-to-face at two dedicated AINI workshops.

PMID- 16111708
TI  - Evidence that intracellular Ca2+ mediates the effect of alpha-ketoisocaproic acid
      on the phosphorylating system of cytoskeletal proteins from cerebral cortex of
      immature rats.
AB  - In this study we investigated the involvement of Ca2+ on the effects of alpha
      ketoisocaproic acid (KIC), the main metabolite accumulating in maple syrup urine
      disease (MSUD), on the phosphorylating system associated with the intermediate
      filament (IF) proteins in slices from cerebral cortex of 9-day-old rats. We first
      observed that KIC significantly decreased the in vitro phosphorylation of IF
      proteins in brain slices. KIC-induced dephosphorylation was mediated especially
      by the protein phosphatase PP2B, a Ca2+-dependent protein phosphatase, but also
      by PP2A. We also demonstrated the involvement of Ca2+-dependent mechanisms in the
      KIC effects using the specific L-voltage-dependent Ca2+ channels (L-VDCC)
      inhibitor nifedipine, the NMDA antagonist DL-AP5 and the intracellular Ca2+
      chelator BAPTA-AM. Blockage of Ca2+ channels or chelating intracellular Ca2+
      completely prevented the effects of KIC on the phosphorylating system associated
      to IF proteins. In addition, we verified that KIC increased 45Ca2+ uptake in
      brain slices after 3 and 30 min incubation. Taken together, our present data
      indicate that KIC increase intracellular Ca2+ levels, probably promoting the
      activation of calcineurin. These results might be associated with the increased
      dephosphorylation of the IF proteins in slices of cerebral cortex of immature
      rats exposed to KIC at similar concentrations from those found in blood and
      tissues of patients with MSUD.

PMID- 16111709
TI  - Omnivory and the stability of food webs.
AB  - The ecological concept of omnivory, feeding at more than a single trophic level,
      is formulated as an intermediate stage between any two of three classical three
      dimensional species interaction systems-tritrophic chain, competition, and
      polyphagy. It is shown that omnivory may be either stabilizing or destabilizing,
      depending, in part, on the conditions of the parent systems from which it
      derives. It is further conjectured that the tritrophic to competition gradient
      cannot be entirely stable, that there must be an instability at some level of
      intermediate omnivory.

PMID- 16111710
TI  - Uncovering the design principles of circadian clocks: mathematical analysis of
      flexibility and evolutionary goals.
AB  - In this paper, we present the mathematical details underlying both an approach to
      the flexibility of regulatory networks and an analytical characterization of
      evolutionary goals of circadian clock networks. A fundamental problem in cellular
      regulation is to understand the relation between the form of regulatory networks
      and their function. Circadian clocks present a particularly interesting instance
      of this. Recent work has shown that they have complex structures involving
      multiple interconnected feedback loops with both positive and negative feedback.
      We address the question of why they have such a complex structure and argue that
      it is to provide the flexibility necessary to simultaneously attain multiple key
      properties of circadian clocks such as robust entrainment and temperature
      compensation. To do this we address two fundamental problems: (A) to understand
      the relationships between the key evolutionary aims of the clock and (B) to
      ascertain how flexible the clock's structure is. To address the first problem we
      use infinitesimal response curves (IRCs), a tool that we believe will be of
      general utility in the analysis of regulatory networks. To understand the second
      problem we introduce the flexibility dimension d, show how to calculate it and
      then use it to analyse a range of models. We believe our results will generalize
      to a broad range of regulatory networks.

PMID- 16111711
TI  - Estimation of the stoichiometry of volatile fatty acid production in the rumen of
      lactating cows.
AB  - The purpose of this study was to improve the prediction of the quantity and type
      of Volatile Fatty Acids (VFA) produced from fermented substrate in the rumen of
      lactating cows. A model was formulated that describes the conversion of substrate
      (soluble carbohydrates, starch, hemi-cellulose, cellulose, and protein) into VFA
      (acetate, propionate, butyrate, and other VFA). Inputs to the model were observed
      rates of true rumen digestion of substrates, whereas outputs were observed molar
      proportions of VFA in rumen fluid. A literature survey generated data of 182
      diets (96 roughage and 86 concentrate diets). Coefficient values that define the
      conversion of a specific substrate into VFA were estimated meta-analytically by
      regression of the model against observed VFA molar proportions using non-linear
      regression techniques. Coefficient estimates significantly differed for acetate
      and propionate production in particular, between different types of substrate and
      between roughage and concentrate diets. Deviations of fitted from observed VFA
      molar proportions could be attributed to random error for 100%. In addition to
      regression against observed data, simulation studies were performed to
      investigate the potential of the estimation method. Fitted coefficient estimates
      from simulated data sets appeared accurate, as well as fitted rates of VFA
      production, although the model accounted for only a small fraction (maximally
      45%) of the variation in VFA molar proportions. The simulation results showed
      that the latter result was merely a consequence of the statistical analysis
      chosen and should not be interpreted as an indication of inaccuracy of
      coefficient estimates. Deviations between fitted and observed values corresponded
      to those obtained in simulations.

PMID- 16111712
TI  - 2-Deoxyglucose: an anticancer and antiviral therapeutic, but not any more a low
      glucose mimetic.
AB  - 2-Deoxyglucose (2-DG), a non-metabolizable glucose analogue, blocks glycolysis
      and inhibits protein glycosylation. It has been tested in multiple studies for
      possible application as an anticancer or antiviral therapeutic. The inhibitory
      effect of 2-DG on ATP generation made it a good candidate molecule as a calorie
      restriction mimetic as well. Furthermore, 2-DG has been utilized in numerous
      studies to simulate a condition of glucose starvation. Because 2-DG disrupts
      glucose metabolism, protein glycosylation, and ER quality control at the same
      time, a cellular or pathologic outcome could be easily misinterpreted without
      clear understanding of 2-DG's effect on each of these aspects. However, the
      effect of 2-DG on protein glycosylation has rarely been investigated. A recent
      study suggested that 2-DG causes hyperGlcNAcylation of proteins, while low
      glucose supply causes hypoGlcNAcylation. In certain aspects of cellular
      physiology, this difference could be disregarded, but in others, this may
      possibly cause totally different outcomes.

PMID- 16111713
TI  - Ethnic differences in CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) genotypes in
      Japanese and Israeli populations.
AB  - CYP2C9 is a major P450 2C enzyme, which hydroxylates about 16% of drugs that are
      in current clinical use and contributes to the metabolism of a number of
      clinically important substrate drugs such as warfarin. Ethnic differences in the
      genetic variation of CYP2C9 have been reported, and might be related to the
      frequencies of adverse reactions to drugs metabolized by CYP2C9 in different
      ethnic groups. In the present study, ethnic differences in the CYP2C9*2 and
      CYP2C9*3 allele distribution in Japanese and Israeli populations were evaluated
      using a newly developed oligonucleotide based DNA array (OligoArray(R)). The
      population studied consisted of 147 Japanese and 388 Israeli donors (100
      Ashkenazi Jews, 99 Yemenite Jews, 100 Moroccan Jews and 89 Libyan Jews). The
      CYP2C9*2 [Arg144Cys (416 C>T), exon 3] and CYP2C9*3 [Ile359Leu (1061 A>C), exon
      7] genotypes were determined using an OligoArray(R). The accuracy of genotyping
      by the OligoArray(R) was verified by the fluorescent dye-terminator cycle
      sequencing method. A Hardy-Weinberg test indicated equilibrium (chi(2)<3.84 is
      Hardy-Weinberg) in all populations. The CYP2C9*2 genotype (CC/CT+TT) was absent
      in Japanese (1/0) (OR 0.02), and its frequency was significant in Libyan Jews
      (0.697/0.303) (OR 2.13; 95% CI 1.07-4.24) compared with Ashkenazi Jews
      (0.83/0.17), Yemenite Jews (0.899/0.101), and Moroccan Jews (0.81/0.19). The
      frequencies of CYP2C9*3 genotype (AA/AC+CC) was significantly lower in Japanese
      (0.986/0.014) (OR 0.08), and was higher in Libyan Jews (0.652/0.348) (OR 3.03;
      95% CI 1.5-6.1) and Moroccan Jews (0.77/0.23) (OR 1.69; 95% CI 0.62-3.48)
      compared with those in Ashkenazi Jews (0.85/0.15) and Yemenite Jews
      (0.849/0.151). Thus, the CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) variants
      were rare in the Japanese population, and showed different frequencies in the
      four Jewish ethnic groups examined.

PMID- 16111714
TI  - Behavioral effects of sinomenine in murine models of anxiety.
AB  - The present study was designed to investigate the putative anxiolytic-like effect
      of sinomenine in three experimental models of anxiety in male rats and mice. Use
      of the elevated plus-maze test revealed that sinomenine (20 and 40 mg/kg, p.o.)
      increased the percentage of open arm entries and diazepam (2 mg/kg, p.o.)
      increased the percentage of open arm entries, the percentage of time spent on
      open arms and total arm entries in mice. In the light/dark transition test,
      sinomenine (20 and 40 mg/kg, p.o.) increased time spent in the light area and
      diazepam (2 mg/kg, p.o.) increased time spent in the light area and the overall
      movements in mice. In the social interaction test, the sinomenine-treated animals
      significantly increased social interaction time in low light unfamiliar (7 mg/kg,
      p.o.) and high light unfamiliar conditions (7 and 14 mg/kg, p.o.) as well as
      diazepam (3 mg/kg, p.o.). Sinomenine (28 mg/kg, p.o.) can also decrease squares
      entered in rats in social interaction test under low light unfamiliar condition.
      In the open-field test, sinomenine (160 mg/kg) decreased squares entered in mice.
      Thus, these findings indicated that sinomenine exhibited anxiolytic-like effect.

PMID- 16111715
TI  - Activation of glucose transport during simulated ischemia in H9c2 cardiac
      myoblasts is mediated by protein kinase C isoforms.
AB  - Glucose transport into cells may be regulated by a variety of conditions,
      including ischemia. We investigated whether some enzymes frequently involved in
      the metabolic adaptation to ischemia are also required for glucose transport
      activation. Ischemia was simulated by incubating during 3 h H9c2 cardiomyoblasts
      in a serum- and glucose-free medium in hypoxia. Under these conditions 2-deoxy-d
      [2,6-(3)H]-glucose uptake was increased (57% above control levels, p<0.0001)
      consistently with GLUT1 and GLUT4 translocation to sarcolemma. Tyrosine kinases
      inhibition via tyrphostin had no effect on glucose transport up-regulation
      induced by simulated ischemia. On the other hand, chelerythrine, a broad range
      inhibitor of protein kinase C isoforms, and rottlerin, an inhibitor of protein
      kinase C delta, completely prevented the stimulation of the transport rate. A
      lower activation of hexose uptake (19%, p<0.001) followed also treatment with
      Go6976, an inhibitor of conventional protein kinases C. Finally, PD98059-mediated
      inhibition of the phosphorylation of ERK 1/2, a downstream mitogen-activated
      protein kinase (MAPK), only partially reduced the activation of glucose transport
      induced by simulated ischemia (31%, p<0.01), while SB203580, an inhibitor of p38
      MAPK, did not exert any effect. These results indicate that stimulation of
      protein kinase C delta is strongly related to the up-regulation of glucose
      transport induced by simulated ischemia in cultured cardiomyoblasts and that
      conventional protein kinases C and ERK 1/2 are partially involved in the
      signalling pathways mediating this process.

PMID- 16111716
TI  - Milk growth factor (MGF) induces transformation into ATDC5 cells,
      prechondrocytes, and cooperates with retinoic acid to transform the cells into
      new forms.
AB  - The effects of milk growth factor (MGF) showed the transformation of ATDC5
      prechondrocytes and differed from that of retinoic acid (RA) as follows. MGF (200
      ng/ml) did not suppress the proliferation of ATDC5 cells, though RA (1 x 10(-7)
      M) suppressed the cell proliferation. However, MGF showed the result as RA, which
      was verified to suppress the production of proteoglycan. The synthesis of
      vimentin in ATDC5 cells was slightly induced by RA, but its withdrawal induced
      the large-scale induction and the fibril formation of vimentin, which may
      indicate that the cells became fibroblastic cells, namely dedifferentiation. MGF,
      which hardly induced the vimentin synthesis in ATDC5 cells, induced its synthesis
      under control by the withdrawal. MGF suppressed the synthesis of alpha-smooth
      muscle actin (alpha-SM-actin), which was apt to reverse in its withdrawal.
      However, RA did not affect this synthesis of ATDC5 cells. The combination of MGF
      and RA enlarged the cells and enhanced the synthesis of vimentin due to RA under
      control, however, almost terminated alpha-SM-actin-synthesis in the cells. And
      its effect is almost irreversible. Furthermore, the combination of MGF and RA
      prevented the induction of fibroblasts due to RA in the cells. And the withdrawal
      of the mixture transformed prechondrocytes into hypertrophic cells. Then, MGF
      contributes to bone metabolism in prechondrocyte.

PMID- 16111717
TI  - Functional and pharmacological mechanisms of nucleoside transport across the
      basolateral membrane of rabbit tracheal epithelial cells.
AB  - The role of basolateral membrane nucleoside transport in primary cultured rabbit
      tracheal epithelial cells (RTEC) was studied. Primary cultured RTEC were grown on
      permeable support at an air-interface. Transport studies were conducted in the
      uptake, efflux, and transepithelial transport configurations using (3)H-uridine
      as a model substrate. Time, temperature and concentration dependency of (3)H
      uridine transport were evaluated in parallel to the metabolism of this substrate
      using scintillation counting and thin layer chromatography. Inhibition of (3)H
      uridine uptake from basolateral fluid was estimated in presence of all unlabeled
      natural nucleosides as well as analogs and nucleobases. Functional modulation
      pathways of (3)H-uridine uptake were studied after treatment of RTEC with
      pharmacological levels of A23187, forskolin, tamoxifen, H89 and colchicine. The
      basolateral aspect has a low-affinity and high-capacity transport system that
      exhibits characteristics of bi-directionality, temperature/concentration
      dependency, and broad specificity towards purines and pyrimidines without
      requiring Na(+). Basolateral equilibrative-sensitive/insensitive (es/ei) type
      transport machinery manifested as a biphasic dose response to nitro-benzyl
      mercapto-purine-ribose (NBMPR) inhibition. In addition, a number of
      therapeutically relevant nucleoside analogs appeared to compete with the uptake
      of uridine from basolateral fluid. Short-term pre-incubation of primary cultured
      RTEC with the calcium ionophore A23187 inhibited basolateral uridine uptake
      without affecting the J(max) and K(m). The inhibitory effect was not reversible
      with a protein kinase C (PKC) antagonist, tamoxifen. In contrast, basolateral
      uridine uptake was increased by adenylyl cyclase activator forskolin (reversible
      with protein kinase A (PKA) inhibitor H89), resulting in a decreased K(m), but a
      lower J(max). Uridine exit across the basolateral membrane of primary cultured
      RTEC occurs via a facilitative diffusion carrier, which can be modulated by
      intracellular Ca(2+) levels and PKA. Information about these carriers will help
      improve the transportability of antitumor and antiviral nucleoside analogs in the
      pulmonary setting.

PMID- 16111718
TI  - The cannabinoid CB2 receptor selective agonist JWH133 reduces mast cell oedema in
      response to compound 48/80 in vivo but not the release of beta-hexosaminidase
      from skin slices in vitro.
AB  - In a recent study so far published in abstract form, it was reported that the
      CB(2) receptor selective agonist AM1241 diminishes oedema produced as a result of
      mast cell degranulation in vivo. It is, however, not known whether other
      structurally different CB(2) agonists share this effect, and whether this is due
      to a direct effect on mast cell function. In the present study, we have
      investigated the effects of JWH133, a CB(2) receptor selective agonist, together
      with the anti-inflammatory agent palmitoylethanolamide and its analogue
      palmitoylisopropylamide, on compound 48/80-induced oedema and degranulation in
      vivo and in vitro. JWH133 (20 and 200 microg/mouse i.p.) significantly reduced
      the ability of compound 48/80 to induce oedema in vivo in the anaesthetised mouse
      following its injection into the ear pinna. Palmitoylethanolamide (200
      microg/mouse i.p) also reduced the response to compound 48/80, whereas no firm
      conclusions could be drawn for palmitoylisopropylamide (20 and 200 microg/mouse
      i.p.). The CB(2) selective antagonist/inverse agonist SR144528 (60 microg/mouse
      i.p.) appeared to produce anti-inflammatory effects per se in this model, making
      it hard to interpret the effects of JWH133 in terms of CB(2) receptor mediated
      activation. In contrast to the situation in vivo, neither JWH133 (0.3 and 3
      microM) nor palmitoylethanolamide (10 microM) affected mast cell degranulation,
      measured by following the release of the granular protein beta-hexosaminidase,
      produced by compound 48/80 in vitro in mouse skin slices. The two compounds were
      also ineffective in inhibiting the binding of [(3)H]pyrilamine to histamine H(1)
      receptors in vitro. It is concluded that the ability of JWH133 to affect mast
      cell dependent inflammation in vivo may be mediated by an indirect action upon
      the mast cells.

PMID- 16111719
TI  - Elevated semicarbazide-sensitive amine oxidase (SSAO) activity in lung with
      ischemia-reperfusion injury: protective effect of ischemic preconditioning plus
      SSAO inhibition.
AB  - Ischemic preconditioning (IP) has been shown to protect the lung against ischemia
      reperfusion (I/R) injury. Although the production of reactive oxygen species
      (ROS) has been postulated to play a crucial role in I/R injury, the sources of
      these radicals in I/R and the mechanisms of protection in IP remain unknown.
      Since it was postulated that deamination of endogenous and exogenous amines by
      semicarbazide-sensitive amine oxidase (SSAO) in tissue damage leads to the
      overproduction of hydrogen peroxide (H2O2), we investigated the possible
      contribution of tissue SSAO to excess ROS generation and lipid peroxidation
      during I/R and IP of the lung. Male Wistar rats were randomized into 6 groups:
      control lungs were subjected to 30 min of perfusion in absence and presence of
      SSAO inhibitor, whereas the lungs of the I/R group were subjected to 2 h of cold
      ischemia following the 30 min of perfusion in absence and presence of SSAO
      inhibitor. IP was performed by two cycles of 5 min ischemia followed by 5 min of
      reperfusion prior to 2 h of hypothermic ischemia in absence and presence of SSAO
      inhibitor. Lipid peroxidation, reduced (GSH) and oxidized (GSSG) glutathione
      levels, antioxidant enzyme activities, SSAO activity, and H2O2 release were
      determined in tissue samples of the study groups. Lipid peroxidation, glutathione
      disulfide (GSSG) content, SSAO activity and H2O2 release were increased in the
      I/R group, whereas GSH content, GSH/GSSG ratio and antioxidant enzyme activities
      were decreased. SSAO activity, H2O2 release, GSSG content and lipid peroxidation
      were markedly decreased in the IP group, whereas GSH content, GSH/GSSG ratio and
      antioxidant enzyme activities were significantly increased. SSAO activity was
      found to be positively correlated with H2O2 production in all study groups.
      Increased lipid peroxidation, SSAO activity, GSSG and H2O2 contents as well as
      decreased GSH and antioxidant enzyme levels in I/R returned to their basal levels
      when IP and SSAO inhibition were applied together. The present study suggests
      that application of IP and SSAO inhibition together may be more effective than IP
      alone against I/R injury in the lung.

PMID- 16111721
TI  - Expression of porcine epidermal growth factor in Pichia pastoris and its biology
      activity in early-weaned piglets.
AB  - Early-weaned piglets often have abnormalities in intestinal morphology and
      function. Epidermal growth factor (EGF) is critical in the development and in the
      repair of the gastrointestinal tract in pigs. This study investigated the effects
      of dietary EGF supplementation on growth performance and small intestinal
      morphology of early-weaned piglets. The functional domain of porcine EGF (pEGF)
      was cloned after RT-PCR amplification. The recombinant protein was expression by
      the Pichia pastoris expression system and the construct pPIC9K-pEGF was
      transformed into host GS115. The secretary recombinant protein in the
      supernatants was analyzed by SDS-PAGE. The gel indicated that the extra band at 6
      kDa in the transformant, which corresponds to the standard hEGF, were both
      reactive to anti-pEGF antibody by Western blotting. The expression level of pEGF
      in the culture supernatant was 870 microg/mL. An animal feeding test was
      conducted to identify the effects of pEGF supplementation on growth performance
      and the development of digestive tracts of 14-day weaned piglets. The dietary
      treatment was a corn-soybean meal basal diet either with or without 1.5 mg/kg
      recombinant pEGF from the transformant fermentative supernatant. Dietary
      treatments enhanced the daily gain during 0-7 days postweaning (p < 0.05), but
      did not affect the performance throughout the entire test period. Dietary
      supplemental pEGF significantly increased serum IgA levels on day 18 postweaning,
      and increased the mucosa IgA levels and crypt depth at jejunum on day 28
      postweaning (p < 0.05). The experimental results showed that the recombinant pEGF
      could be secreted by P. pastoris. The trophic effects of pEGF on growth
      performance, immune response, and small intestine development were determined by
      feeding recombinant pEGF to early-weaned piglets.

PMID- 16111720
TI  - The effect of PKC activity on the TTX-R sodium currents from rat nodose ganglion
      neurons.
AB  - To determine how protein kinase C (PKC) activity influences properties of the
      tetrodotoxin-resistant sodium current (TTX-R I(Na)) in neonatal rat nodose
      ganglion (NG) neurons, we assessed the effects of phorbol,-12-myristate,13
      acetate (PMA), one of the PKC activators, and staurosporine, one of the PKC
      inhibitors, on the current. PMA (30 and 100 nM) induced an increase in the peak
      current amplitude of normalized current-voltage curves, a leftward shift in the
      potential for half activation (V(1/2)) of normalized conductance-voltage curves
      and a leftward shift of V(1/2) potential for steady-state inactivation curves.
      The effects of staurosporine (0.1 and 1 muM) on the peak current amplitude and
      the V(1/2) potential for activation were opposite compared with those seen after
      PMA application. Staurosporine (1 muM) antagonized PMA (100 nM)-induced
      modification of TTX-R I(Na). These results suggest that the basal TTX-R I(Na)
      obtained from neonatal NG neurons is controlled by the level of PKC activity.

PMID- 16111722
TI  - Knockdown of Ki-67 by small interfering RNA leads to inhibition of proliferation
      and induction of apoptosis in human renal carcinoma cells.
AB  - To investigate the effect of small-interfering RNA (siRNA) targeted against Ki
      67, which is an attractive molecular target for cancer therapy, on inhibiting Ki
      67 expression and cell proliferation in human renal carcinoma cells (HRCCs),
      siRNAs were used to inhibit the expression of Ki-67 in HRCCs. Ki-67 mRNA levels
      were detected by RT-PCR and in situ hybridization analysis. Ki-67 protein levels
      were detected by Western blot and immunocytochemistry analysis. TUNEL assay was
      used to measure the apoptosis of carcinoma cells. Results of RT-PCR and in situ
      hybridization demonstrated reduction of Ki-67 mRNA expression in Ki-67 siRNAs
      treated 786-0 cells. Similar reduction in Ki-67 protein measured by Western blot
      and immunocytochemistry was observed in cells transfected with Ki-67 siRNA. Ki-67
      siRNA treatment of HRCCs resulted in specific inhibition of proliferation and
      increased apoptotic cell death. From these findings we conclude that inhibition
      of Ki-67 expression by siRNA may be a reasonable approach in renal cancer
      therapy.

PMID- 16111723
TI  - Distribution and enrichment evaluation of heavy metals in Mejillones Bay (23
      degrees S), Northern Chile: geochemical and statistical approach.
AB  - A suite of 36 surface sediment samples, taken between 10 and 100 m water depth in
      Mejillones Bay (Northern Chile), were analyzed for mineralogy, grain size, total
      organic carbon, Al, and heavy metal content (Cd, Zn, Ni, Mn, V, Mo). Quartz and
      feldspars were the main lithogenic minerals and carbonate the predominant
      biogenic mineral. Sediments were fine sands in the shallow zone and organic silt
      in the deeper zone. Enrichment Factor and Factor Analysis approach showed that
      the presence of Mn in the marine sediment of Mejillones is due to a partial
      influence of continental input, while all other metals are not supported by
      lithogenic debris. Although all metals showed high concentrations in the marine
      sediment of Mejillones Bay, comparison between metal concentration in surface
      sediments and preindustrial levels in this bay, show that present values agree
      with natural levels.

PMID- 16111724
TI  - Selective cortical VGLUT1 increase as a marker for antidepressant activity.
AB  - The two recently characterized vesicular glutamate transporters (VGLUT)
      presynaptically mark and differentiate two distinct excitatory neuronal
      populations and thus define a cortical and a subcortical glutamatergic system
      (VGLUT1 and VGLUT2 positive, respectively). These two systems might be
      differentially implicated in brain neuropathology. Still, little is known on the
      modalities of VGLUT1 and VGLUT2 regulations in response to pharmacological or
      physiological stimuli. Given the importance of cortical neuronal activity in
      psychosis we investigated VGLUT1 mRNA and protein expression in response to
      chronic treatment with commonly prescribed psychotropic medications. We show that
      agents with antidepressant activity, namely the antidepressants fluoxetine and
      desipramine, the atypical antipsychotic clozapine, and the mood stabilizer
      lithium increased VGLUT1 mRNA expression in neurons of the cerebral cortex and
      the hippocampus and in concert enhanced VGLUT1 protein expression in their
      projection fields. In contrast the typical antipsychotic haloperidol, the
      cognitive enhancers memantine and tacrine, and the anxiolytic diazepam were
      without effect. We suggest that VGLUT1 could be a useful marker for
      antidepressant activity. Furthermore, adaptive changes in VGLUT1 positive neurons
      could constitute a common functional endpoint for structurally unrelated
      antidepressants, representing promising antidepressant targets in tracking
      specificity, mechanism, and onset at action.

PMID- 16111725
TI  - Visual spatial and visual pattern working memory: neuropsychological evidence for
      a differential role of left and right dorsal visual brain.
AB  - According to neurophysiological, neuroimaging, and behavioural evidence, visual
      working memory (WM) can be separated into a "what" and a "where" component,
      reflecting the duality of visual processing. Whereas a wealth of empirical data
      suggests a right-sided fronto-parietal network critical for the maintenance of
      spatial information, the cortical structures underlying maintenance of object
      information have remained controversial. Although visual object processing
      depends on ventral, inferior temporal areas, recent neuroimaging results suggest
      that maintenance of visual object information involves a left-sided or bilateral
      fronto-parietal network. The aim of the present study is to further clarify the
      role of the left and right parietal lobes for pattern and spatial visual WM.
      Seven patients with left-sided, seven with right-sided parietal brain injury, and
      two age-matched healthy control groups performed a delayed-matching-to-sample
      task using either pattern (shape) or spatial (location) information or both. In
      addition, eight patients with left-sided injury sparing parietal areas were
      tested to further examine the specific role of the left parietal cortex in
      pattern WM. Left parietal injury resulted in pattern WM impairment, only, while
      right parietal injury was associated with pattern and spatial WM deficits. Non
      parietal injury was not associated with comparable deficits. These results
      suggest that visual spatial WM depends critically on right parietal areas; in
      contrast, pattern WM depends on both, left and right parietal areas.

PMID- 16111726
TI  - Phenolic compounds from the fruit of Garcinia dulcis.
AB  - Dulcinoside (1), dulcisisoflavone (2), dulcisxanthone A (3) and sphaerobioside
      acetate (6) together with 22 known compounds were isolated from the green fruit
      of G. dulcis. Dulcisflavan (4), dulcisxanthone B (5) and isonormangostin (7)
      together with 22 known compounds were isolated from the ripe fruit. Compounds 6
      and 7 were synthetic known compounds. Their structures were determined by
      spectroscopic methods. The radical scavenging and antibacterial activities of
      some of the compounds were investigated.

PMID- 16111727
TI  - Haemoglobin variants and anaemia among pre-school/school children in north-east
      Brazil.
AB  - In this study we investigated the presence of haemoglobin (Hb) variants and
      anaemia among 382 pre-school/school children from Bahia State, Brazil, a state
      where intermixing involving people from African origin is the highest in the
      country. Hb variants were investigated by cellulose acetate electrophoresis at
      alkaline pH. The pattern obtained was confirmed by citrate agar electrophoresis
      at pH 6.2. From the 382 children investigated, 79 (20.7%) had Hb variants: 47
      (59.5%) had HbAS, 28 (35.4%) HbAC, 3 (3.8%) HbSC and 1 (1.3%) HbCC. Two hundred
      and fourteen children had anaemia. From these, 39 had microcytosis and 14 had low
      values of ferritin (<12 ng/ml). We cannot exclude thalassaemia among the children
      with microcytosis and hypochromia because it was not investigated. The majority
      of the children showed high mean values of ferritin, suggestive of subclinical
      infection. There was no difference when we compared the prevalence of anaemia
      among children with Hb variants (65.8%) and those without Hb variants (53.5%) (P
      = 0.06). These data demonstrate that Hb variants and anaemia are probably
      important public health problems in north-east Brazil.

PMID- 16111728
TI  - Enterocytozoon bieneusi (microsporidia) in clinical samples from immunocompetent
      individuals in Tenerife, Canary Islands, Spain.
AB  - Microsporidia are newly emerging pathogens of humans and animals, with
      Enterocytozoon bieneusi being the most common causal agent in human
      microsporidiosis. To determine the presence of E. bieneusi, 273 clinical samples
      (40 urine, 156 stools, 37 sputum, 9 bronchial aspirates, 5 bronchial washes and
      26 pleural fluids) from immunocompetent patients, mainly suffering diarrhoea or
      pneumonia, in Tenerife, Canary Islands, Spain were analysed using light
      microscopy after staining with Weber's chromotrope and by PCR/hybridisation with
      a specific probe designed to increase the sensitivity of the identification. In
      this study, detection of E. bieneusi after PCR/hybridisation is reported in 18
      (11.54%) of 156 stool samples, 1 (2.5%) of 40 urine samples and 6 (16.22%) of 37
      sputum samples. To our knowledge, these are the first reports of E. bieneusi in
      this subtropical region, showing the increased importance of these parasites as
      emerging pathogens worldwide.

PMID- 16111729
TI  - Clinical presentation of melioidosis in Queensland, Australia.
AB  - A retrospective study was performed on culture-positive patients (n = 57) with
      melioidosis presenting to the Townsville Hospital to define the epidemiology of
      the disease in Queensland, Australia. Mortality was 25% (n = 14) with a 9% (n =
      5) relapse rate. At presentation, primary organs involved included the lungs
      (58%; n = 33), genitourinary system (11%; n = 6), skin and soft tissue (9%; n =
      5), bone and joints (4%; n = 2), central nervous system (4%; n = 2), mycotic
      aneurysm (2%; n = 1) and peritonitis (2%; n = 1). No focus of infection could be
      identified in 12% of cases (n = 7). There was no significant difference in the
      clinical presentation of melioidosis in Queensland compared with the Northern
      Territory. Regional trends in the clinical presentation of melioidosis in
      Australia compared with Southeast Asia were confirmed. Risk factors for disease
      included diabetes (42%), excess alcohol consumption (42%), chronic lung disease
      (26%), immunosuppressive drug use (12%), renal disease (11%), malignancy (7%) and
      autoimmune disease (5%). No risk factors were identifiable in 18% of cases. The
      presence of multiple risk factors for melioidosis was not significantly
      associated with increased mortality (P > 0.05).

PMID- 16111730
TI  - Toxoplasmic meningoencephalitis in an immunocompetent host.
AB  - Central nervous system involvement due to toxoplasmosis in an immunocompetent
      host is very rare. We report a case of an immunocompetent patient who presented
      with suspected tuberculous meningoencephalitis but showed no clinical response to
      antitubercular therapy. Later, toxoplasmic meningoencephalitis was proved by
      positive serological testing for toxoplasmosis, supportive magnetic resonance
      imaging findings of the brain and a therapeutic response to co-trimoxazole and
      prednisolone. Therefore, toxoplasmosis should be considered in cases of suspected
      tuberculous meningoencephalitis that fail to respond to specific therapy.

PMID- 16111731
TI  - Differentiation and diversification of follicular cells in polytrophic ovaries of
      crane flies (Diptera: Nematocera: Tipulomorpha and Trichoceridae).
AB  - To gain insight into the evolution of differentiation pathways that are involved
      in the follicular cells' morphogenesis in dipteran ovaries we have undertaken the
      comparative morphological analysis of the follicular cell behavior in crane
      flies, representatives of more ancestral nematocerous flies. This analysis
      revealed that initially the organization of the follicular epithelium in the
      species under study shows significant similarities to that reported in the
      ovaries of true flies (Brachycera), indicating that the ancestors of dipterans
      must have evolved a common and specific system of the early patterning of their
      follicular epithelium. On the other hand, in contrast to Drosophila and other
      advanced brachycerans, the follicular cells in the studied nematoceran ovaries do
      not exhibit any migratory activity. Instead, they were found to change their
      relative position but only within the epithelial layer. These "translocations"
      appeared to depend merely on cell shape changes. Although the "immobility" of the
      follicular cells in the ovaries of crane flies results in the lower number of
      their specialized subgroups when compared with the true flies, the functional
      homology between particular subsets of follicular cells can be postulated. We
      suggest that the anterior polar cells and the micropyle forming anterior terminal
      follicular cells in crane fly ovaries have their counterparts in the brachyceran
      anterior polar cells and border cells, respectively.

PMID- 16111732
TI  - West Nile virus replication interferes with both poly(I:C)-induced interferon
      gene transcription and response to interferon treatment.
AB  - West Nile virus (WNV), the leading cause of viral encephalitis in the United
      States, is an arthropod-transmitted member of the family Flaviviridae. We have
      explored the interaction of this positive-strand RNA virus with signaling
      pathways involved in induction of the host's innate immune response.
      Phosphorylation of STAT-1 in response to interferon (IFN) treatment and the
      ability of IFN to establish an antiviral state were reduced in WNV replicon
      bearing cell lines. Similarly, the activation of IRF3 and stimulation of IFN-beta
      transcription in response to the double-stranded RNA (dsRNA) mimetic poly(I:C)
      were inhibited in replicon-bearing and WNV-infected HeLa cells. In contrast, WNV
      replicons did not affect IRF3 activation by Sendai virus infection, suggesting
      that not all IRF3 activating pathways are inhibited by WNV. Taken together, these
      findings demonstrate that WNV replication in cultured cells interferes with both
      the response to IFN and synthesis of IFN-beta in response to dsRNA.

PMID- 16111733
TI  - Foveal processing difficulty does not modulate non-foveal orthographic influences
      on fixation positions.
AB  - Two experiments show that eye fixations land nearer to the beginning of
      misspelled than correctly spelled beginning words during sentence reading. The
      effect holds regardless of whether the previous word is easy (high frequency) or
      difficult (low frequency) to process. In Experiment 1, the misspelled words were
      directly fixated. In Experiment 2, a saccade contingent change technique was used
      such that the words were always correctly spelled once they were fixated. The
      results show that non-foveal orthography influences where words are first fixated
      regardless of foveal processing load.

PMID- 16111734
TI  - Assessment of heavy metal levels in Almendares River sediments--Havana City,
      Cuba.
AB  - The Almendares River watershed covers a large portion of Havana, Cuba and is
      centrally important to both recreational and other activities in the region. In
      order to assess current water quality conditions prior to planned remediation
      efforts, the spatial distribution of six heavy metals and other compounds were
      determined in river sediments at fifteen sampling stations in the watershed.
      Metal concentrations in sediments ranged from 86.1 to 708.8 for Zn, 39.3 to 189.0
      for Pb, 71.6 to 420.8 for Cu, 84.4 to 209.7 Cr, 1.5 to 23.4 for Co, and 1.0 to
      4.3 for Cd microg/g dry weight sediment. Calculated enrichment factors (EF;
      measured metal versus background mineral conditions) were almost always greater
      than 1.0, suggesting significant anthropogenic impact on metal levels in the
      river. The highest EF values were seen immediately below Cotorro (EF>10 for Pb,
      Cu, and Cd), a suburban town that has an active secondary smelter, and below the
      largest municipal landfill in Havana (EF>10 for Pb, Cu, Cd, and Zn). Further,
      three sampling stations had multiple metals at concentrations higher than
      probable effects concentrations (PEC), implying possible local ecotoxicological
      impacts. Finally, sequential extractions of the sediments indicated that heavy
      metals were largely associated with the organic fraction, and it was estimated
      that up to 62% of metals in the sediments would be susceptible to release back
      into the water column if hydraulic or other changes occurred in the river. These
      data are being used to prioritize decisions related to the remediation of the
      river system.

PMID- 16111735
TI  - Catalytic wet peroxide oxidation of phenol by pillared clays containing Al-Ce-Fe.
AB  - A Colombian bentonite was successfully pillared with mixed polyhydroxocationic
      solutions of Al-Fe or Al-Ce-Fe, with the iron in small quantities, to generate a
      modified Fenton process on the surface of the pillared clays with a possible
      activation of the hydrogen peroxide and the organic substances on the iron sites
      of the solids in order to obtain active and stable catalysts for the wet peroxide
      oxidation of organic pollutants from industrial wastewaters. The catalysts were
      very efficient in the reaction of phenol oxidation in diluted aqueous media under
      mild experimental conditions (298 K and atmospheric pressure) and in the
      elimination of the different intermediary compounds of the reaction reaching high
      mineralization levels. The solids showed high stability in the reaction media due
      to the strong interaction between the iron species and the catalyst support. The
      incorporation of Ce in the solids showed a favorable effect in the pillaring of
      the materials allowing the increase of the basal spacing and enhancing the
      catalytic activity of the solids.

PMID- 16111736
TI  - Enhanced granulation by natural ionic polymer additives in UASB reactor treating
      low-strength wastewater.
AB  - Effect of natural ionic polymer additives on granulation in lab-scale UASB
      reactors treating low-strength synthetic wastewater (COD 750-850 mg/L) was
      examined. The organic loading rate was 1.477+/-0.118 kgCOD/m3/day. Under
      identical conditions four similar reactors were operated in parallel with the
      following additives: control with no additive, anionic part of Reetha (Sapindus
      trifoliata) extract, cationic part of Reetha extract, and Chitosan. By the end of
      the study period, Chitosan as an additive produced largest granules with mean
      size of 0.15 mm closely followed by the cationic fraction of the Reetha extract
      with mean size of 0.144 mm, and anionic fractions of the Reetha extract with
      0.139 mm. Control reactor with no additives had the smallest size granules with
      mean size of 0.128 mm. The fraction of granules in the sludge bed of size >0.1 mm
      showed similar trend. The largest granule size observed in the reactors with
      additives was 4-5mm as compared to 2 mm in the control reactor. Cationic polymers
      were more effective additives for enhancing sludge granulation. Exo-cellular
      protein, lipid, sugar and total polymer increased with granulation in the
      reactors. A COD removal efficiency of 95-98% was achieved in all the reactors.

PMID- 16111737
TI  - Effect of surfactants on desorption of aldicarb from spiked soil.
AB  - Surfactant enhanced desorption of aldicarb from spiked soil was investigated in
      this paper. Anionic (sodium dodecyl benzene sulphonate, SDBS), cationic
      (hexadecyl trimethyl ammonium bromide, HTAB) and nonionic (octyl polyethylene
      glycol phenyl ether, OP) surfactants were tested to determine their optimal
      desorption conditions including desorption time, mixing speed and surfactant
      concentrations. The results showed that the optimal operating conditions were
      obtained at 2 h, 150 rpm, and surfactants concentrations were 1000, 100, and 200
      mg l(-1) for SDBS, OP, and HTAB, respectively. The paper also investigated the
      desorption efficiency of mixture of different kinds of surfactants for aldicarb
      spiked soil, and found that anionic-nonionic surfactant mixtures gave the best
      desorption efficiency up to 77%, while anionic-cationic surfactant mixture gave a
      poor desorption efficiency similar to water, suggesting that mixture of anionic
      nonionic surfactants were highly promising on remediation of aldicarb
      contaminated soil.

PMID- 16111738
TI  - p21WAF/CIP1/SDI1 is upregulated due to increased mRNA stability during
      hydroxyurea-induced senescence of human fibroblasts.
AB  - Hydoxyurea induces senescence-like growth arrest in normal human fibroblasts.
      p21(WAF/CIP1/SDI1), a cyclin dependent kinase inhibitor, was found to be
      upregulated during this growth arrest. Levels of p21(WAF/CIP1/SDI1) protein and
      mRNA were increased nine-fold by hydroxyurea in these cells. In order to
      determine whether p21(WAF/CIP1/SDI1) mRNA is increased by hydroxyurea at the
      transcriptional level, human fibroblast cells were transfected with reporter
      constructs containing a p21(WAF/CIP1/SDI1) promoter fragment and then treated
      with hydroxyurea. The luciferase activities in the reporter-transfected
      fibroblast cells were not increased by hydroxyurea, indicating that
      p21(WAF/CIP1/SDI1) transcription was not elevated by hydroxyurea. The half-life
      of the p21(WAF/CIP1/SDI1) mRNA was increased by 2.5-fold but that of
      p21(WAF/CIP1/SDI1) protein was not. Our results suggest that increased mRNA
      stability is the major mechanism of p21(WAF/CIP1/SDI1) elevation in the
      hydroxyurea-induced growth arrest of human fibroblasts.

PMID- 16111739
TI  - Nifedipine potentiates antinociceptive effects of morphine in rats by decreasing
      hypothalamic pituitary adrenal axis activity.
AB  - It has been shown that nifedipine, as a calcium channel blocker can potentiate
      the antinociceptive effect of morphine; however, the role of Hypothalamic
      Pituitary-Adrenal (HPA) axis on this action has not been elucidated. We examined
      the effect of nifedipine on morphine-induced analgesia in intact and
      adrenalectomized (ADX) rats and on HPA activity induced by morphine. To determine
      the effect of nifedipine on morphine analgesia, nifedipine (2 mg/kg i.p.) that
      had no antinociceptive effect, was injected concomitant with sub-effective dose
      of morphine (1 and 2 mg/kg). The tail-flick test was used to assess the
      nociceptive threshold, before and 15, 30, 60, 90, 120 and 180 min after drug
      administration. Our results showed that, nifedipine could potentiate the
      antinociceptive effect of morphine and this effect of nifedipine in ADX was
      greater than sham operated rats which, was reversed by corticosterone
      replacement. Nifedipine has an inhibitory effect on morphine -induced
      corticosterone secretion. Thus, the data indicate that the mechanism underlying
      the potentiation of morphine analgesia by nifedipine involves mediation, at least
      in part, by attenuating the effect of morphine on HPA axis.

PMID- 16111740
TI  - Effect of short- vs. long-term estrogen on reinstatement of cocaine-seeking
      behavior in female rats.
AB  - Estrogen effects on cocaine-induced reinstatement of lever responding were
      examined in sham-operated, vehicle-treated (SH+VEH), ovariectomized (OVX+VEH),
      and OVX female Wistar rats with estrogen replacement (OVX+EB). The effect of long
      (64+/-1.56 days) and short-term (9 days) EB treatment on reinstatement of
      cocaine-seeking behavior was compared in Experiment 1 and 2, respectively, in
      order to compare the effect of EB when it was present during the development vs.
      expression of reinstatement of cocaine-seeking behavior. Rats were trained to
      self-administer 0.4 mg/kg/inf cocaine. After the acquisition criteria were met,
      rats continued to respond for cocaine for 2 h/day for a 14-day maintenance
      period. Cocaine was then replaced with saline and the 21-day extinction period
      commenced. Subsequently, rats were tested for reinstatement of lever responding
      on the previously drug-paired lever after alternating daily injections of saline
      or cocaine. In both experiments, there were no differences between groups in self
      administration behavior during training, maintenance, or extinction. In
      Experiment 1, SH+VEH and chronically treated OVX+EB rats had greater cocaine
      induced reinstatement than OVX+VEH rats. In Experiment 2, short-term treated
      OVX+EB rats also showed enhanced cocaine-induced reinstatement compared to
      OVX+VEH rats. The results indicate that EB-mediated enhancement of cocaine
      induced reinstatement is dependent on EB presence during the expression of
      reinstatement but not during the formation of stimulus-reward associations during
      the development of cocaine-reinforced behavior.

PMID- 16111741
TI  - Changes in the expression of estrogen receptor mRNA in the utero-vaginal junction
      containing sperm storage tubules in laying hens after repeated artificial
      insemination.
AB  - The objective was to determine whether expression of estrogen receptor (ER) mRNA
      in the utero-vaginal junction (UVJ) of laying hens was altered after repeated
      artificial insemination (AI). Semi-quantitative RT-PCR was used to determine the
      expression of mRNA of the two types of receptor, ERalpha and ERbeta. Only ERalpha
      mRNA was expressed in all segments of the oviducts of both virgin and
      artificially inseminated birds, whereas ERbeta mRNA was expressed in ovarian
      follicles but not in the oviduct. The expression of ERalpha mRNA in the UVJ was
      significantly decreased after repeated AI, whereas that in the uterus was not
      significantly different between virgin and inseminated birds. Since estrogen may
      be involved in maintaining the sperm storage function of sperm storage tubules,
      the decreased expression of ERalpha mRNA in the UVJ after repeated AI may
      contribute to reduced fertility in these birds.

PMID- 16111742
TI  - The preservation of verb subcategory knowledge in a spoken language comprehension
      deficit.
AB  - Patient WBN has a lexical-semantic deficit resulting in impaired performance on
      language comprehension tasks that require access to verb meanings in both single
      word and sentence contexts. However, WBN shows no such comprehension impairment
      with respect to lexical syntax. Specifically, he performs without error on
      comprehension tasks that rely on knowledge of lexical-specific verb subcategory
      requirements. This performance pattern supports theories of lexical
      representation and processing in which lexical syntactic information may be
      encoded and retrieved independently from lexical semantic information.

PMID- 16111743
TI  - DNA as a matrix of collagen fibrils.
AB  - In this paper we demonstrate that DNA binds to collagen directly to form DNA
      collagen complex. Our model suggests that DNA, containing well-arranged phosphate
      groups, helps the collagen to make ordered aggregates-fibrils. During this
      process hydration shell of collagen triple helix destroys and stabilizes
      hydration shell of ds-DNA.

PMID- 16111744
TI  - Electrospinning of collagen and elastin for tissue engineering applications.
AB  - Meshes of collagen and/or elastin were successfully prepared by means of
      electrospinning from aqueous solutions. Flow rate, applied electric field,
      collecting distance and composition of the starting solutions determined the
      morphology of the obtained fibres. Addition of PEO (M(w)=8 x 10(6)) and NaCl was
      always necessary to spin continuous and homogeneous fibres. Spinning a mixture of
      collagen and elastin resulted in fibres in which the single components could not
      be distinguished by SEM. Increasing the elastin content determined an increase in
      fibres diameters from 220 to 600 nm. The voltage necessary for a continuous
      production of fibres was dependent on the composition of the starting solution,
      but always between 10 and 25 kV. Under these conditions, non-woven meshes could
      be formed and a partial orientation of the fibres constituting the mesh was
      obtained by using a rotating tubular mandrel as collector. Collagen/elastin (1:1)
      meshes were stabilized by crosslinking with N-(3-dimethylaminopropyl)-N'
      ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). This
      treatment afforded materials with a high thermal stability (T(d)=79 degrees C)
      without altering their original morphology. Upon crosslinking PEO and NaCl were
      fully leached out. Smooth muscle cells grew as a confluent layer on top of the
      crosslinked meshes after 14 d of culture.

PMID- 16111745
TI  - A new in vivo screening model for posterior spinal bone formation: comparison of
      ten calcium phosphate ceramic material treatments.
AB  - This study presents a new screening model for evaluating the influence of
      multiple conditions on the initial process of bone formation in the posterior
      lumbar spine of a large animal. This model uses cages designed for placement on
      the decorticated transverse process of the goat lumbar spine. Five conduction
      channels per cage, each be defined by a different material treatment, are open to
      both the underlying bone and overlying soft tissue. The model was validated in
      ten adult Dutch milk goats, with each animal implanted with two cages containing
      a total of ten calcium phosphate material treatments according to a randomized
      complete block design. The ten calcium phosphate ceramic materials were created
      through a combination of material chemistry (BCP, TCP, HA), sintering temperature
      (low, medium, high), calcination and surface roughness treatments. To monitor the
      bone formation over time, fluorochrome markers were administered at 3, 5 and 7
      weeks and the animals were sacrificed at 9 weeks after implantation. Bone
      formation in the conduction channels was investigated by histology and
      histomorphometry of non-decalcified sections using traditional light and
      epifluorescent microscopy. According to both observed and measured bone formation
      parameters, materials were ranked in order of increasing magnitude as follows:
      low sintering temperature BCP (rough and smooth) approximately medium sintering
      temperature BCP approximately = TCP > calcined low sintering temperature HA > non
      calcined low sintering temperature HA > high sintering temperature BCP (rough and
      smooth) > high sintering temperature HA (calcined and non-calcined). These
      results agree closely with those obtained in previous studies of osteoconduction
      and bioactivity of ceramics thereby validating the screening model presented in
      this study.

PMID- 16111746
TI  - Novel hepatocyte culture system developed using microfabrication and
      collagen/polyethylene glycol microcontact printing.
AB  - The better understanding of cell biology and cell communication requires novel
      culture systems that better represent the natural cell environment in tissues and
      organs. We developed a spherical organoid (spheroid) microarray culture system
      using a combination of microfabrication and microcontact printing. The system
      consisted of a chip that had cylindrical cavities of 300 microm diameter at a
      density of 700 cavities/cm2. The bottom faces of these cavities were defined as
      two different regions that either supported or inhibited cell adhesion. In the
      cell adhesion region, the center of the bottom face of a 100 microm diameter in a
      cavity was modified with collagen (Col), and in the non-adhesion region, the
      entire region around the cavity, except the Col spots, was modified with
      polyethylene glycol. Primary hepatocytes spontaneously formed spheroids with a
      uniform diameter at the center of each cavity on the chip. Hepatocytes forming
      spheroids had a cuboidal cell shape, similar to hepatocytes in vivo, and stably
      maintained liver-specific phenotypes, such as liver-enriched transcriptional
      factors, albumin secretion, urea cycle enzymes, and intercellular adhesion
      molecules. This novel culture system may be applicable as a cellular platform for
      fundamental studies in cell biology and tissue engineering applications.

PMID- 16111747
TI  - NAADP receptors.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) is a recently described
      Ca2+ mobilizing messenger. First described in the sea urchin egg, it has been
      shown to mobilize Ca2+ from intracellular stores. It is a remarkably potent
      molecule, and recent reports show that its cellular levels change in response to
      a variety of agonists confirming its role as a Ca2+ mobilizing messenger. In many
      cases NAADP interacts with other Ca2+ mobilizing messengers such as inositol
      1,4,5 trisphosphate (IP3 and cyclic adenosine diphosphate ribose (cADPR) in
      shaping cytosolic Ca2+ signals. What is not clear is the molecular nature of the
      NAADP-sensitive Ca2+ release mechanism and its sub-cellular localization. In this
      review we focus on the recent progress made in sea urchin eggs, which indicates
      that NAADP activates a novel Ca2+ release channel distinct from the relatively
      well-characterized IP3 and ryanodine receptors. Furthermore, in the sea urchin
      egg, the NAADP-sensitive store appears to be separate from the endoplasmic
      reticulum (ER) and is most likely an acidic store. These findings have also been
      reinforced by similar findings by some in mammalian cells. Finally, we discuss
      ongoing strategies to characterise NAADP-binding proteins which will greatly
      enhance our understanding of NAADP-mediated Ca2+ signalling, and lead to the
      development of more selective tools to probe the role of this messenger.

PMID- 16111748
TI  - Functional integrity in vitro of hematopoietic progenitor cells from patients
      with chronic myeloid leukemia that have achieved hematological remission after
      different therapeutic procedures.
AB  - In this study, we have assessed the in vitro growth of hematopoietic progenitor
      cells (HPC) from chronic myeloid leukemia (CML) patients that have recovered
      after different treatments. Bone marrow cells were obtained from 33 CML patients,
      including patients at diagnosis, before treatment (n=12), and patients that have
      achieved hematological remission (and in most cases a major cytogenetic response)
      after different therapeutic procedures (n=21), including patients treated with
      Interferon-alpha (IFN; n=5), imatinib mesylate (IMATINIB; n=8) and patients that
      received an allogeneic hematopoietic cell transplant (HCT; n=8). Marrow cells
      were enriched for CD34(+) cells and cultured in a serum- and stroma-free liquid
      culture system, supplemented with a combination of 8 recombinant cytokines.
      Normal samples were studied as controls. HPC from CML patients before therapy
      showed deficient proliferation and expansion potentials in culture (140-fold
      increase in nucleated cell number and 1.3-fold increase in colony-forming cell
      number) as compared to normal progenitors (1200-fold increase in nucleated cell
      number and 25-fold increase in colony-forming cell number). In contrast, HPC from
      patients treated with IMATINIB showed growth potentials similar to those of
      normal progenitors. Progenitors from patients after HCT also showed significant
      proliferation and expansion capacities. Interestingly, progenitors from IFN
      treated patients showed proliferation and expansion kinetics similar to those of
      cells from untreated patients. These results indicate that, although treatment of
      CML patients with IFN, IMATINIB or HCT resulted in complete hematological
      remission (and a major cytogenetic response), only patients treated with IMATINIB
      and, to a lesser extent, with HCT showed a full hematopoietic recovery, as
      determined by the in vitro growth of HPC in our culture system.

PMID- 16111750
TI  - Ploidy status rarely changes in myeloma patients at disease progression.
AB  - Hyperdiploid and non-hyperdiploid multiple myeloma represents distinct biological
      entities characterized by different patterns of genetic changes. We sought to
      determine whether ploidy category (non-hyperdiploid versus hyperdiploid) remains
      stable over time from diagnosis to progression. Of the 43 patients studied (39 by
      flow cytometry DNA index and 4 by a FISH-based index), only five (12%) altered
      their ploidy status at progression. In three of these patients, the change may
      possibly be attributable to technical artifacts because of the low absolute
      change in DNA index. For those who retain their ploidy subtypes, the DNA index
      change minimally (3.75+/-4.87%). It would appear that the initiating genetic
      events underlying hyperdiploid and non-hyperdiploid MM that marks them out as
      distinct entities continue to dominate and persist during disease evolution and
      progression.

PMID- 16111749
TI  - Bortezomib (Velcade) for progressive myeloma after autologous stem cell
      transplantation and thalidomide.
AB  - Twenty-one patients with multiple myeloma, all relapsed after frontline
      autologous stem cell transplantation and all relapsed again after or resistant to
      thalidomide (employed as second line treatment) received bortezomib (1.3 mg/m(2)
      body surface twice weekly for 2 weeks followed by an interval of 10-12 days)
      without adjunct of steroids as third line therapy. Three patients died of
      progressive disease during the first 2 cycles with bortezomib. Eighteen patients
      received at least 2 cycles and were evaluated for response. According to EBMT
      criteria, two complete (negative immunofixation) and seven partial (reduction of
      M-component > 50-75%) remissions were achieved (ITT response rate 42.8%).
      Duration of response lasted from 2 to 14+ months. Grades 3-4 toxicities
      (thrombocytopenia, leucopenia, peripheral neuropathy and vasculitis) were
      observed in seven patients, but no patient interrupted the treatment due to side
      effects. We conclude that bortezomib alone may induce high quality responses as
      third line salvage therapy with acceptable toxicity in a significant proportion
      of homogeneously pre-treated myeloma patients with progressive disease after
      autologous transplantation and thalidomide.

PMID- 16111751
TI  - Neural activation during cat odor-induced conditioned fear and 'trial 2' fear in
      rats.
AB  - Exposure to cat odor, an innate threat stimulus for rats, engages a conditioning
      process whereby the environment in which the odor was experienced comes to elicit
      fear. Additionally, response to cat odor appears to change with repeated
      exposure, with benzodiazepines having an anxiolytic effect upon first, but not
      second, cat odor exposure. We explored the neural correlates of these two
      phenomena using Fos immunohistochemistry. Rats were exposed to cat odor (a worn
      cat collar) and were allowed to hide from this stimulus. A 'trial 1' group was
      perfused after a single exposure, and a 'trial 2' group after two exposures. A
      'context' group was exposed to cat odor once, then perfused after re-exposure to
      the odor-paired context. Trial 1, trial 2 and context groups showed similar
      defensive responses including avoidance and hiding. The trial 1 group showed Fos
      expression in limbic, hypothalamic and brainstem regions associated with
      defensive behavior. The trial 2 group showed a similar pattern although with less
      activation in the lateral septum, anterior and ventromedial hypothalamus, and
      dorsolateral periaqueductal gray. The context-exposed group showed Fos expression
      in a subset of the regions activated by cat odor itself: the dorsal premammillary
      nucleus, ventrolateral periaqueductal grey, cuneiform nucleus and locus ceruleus.
      Little activation was seen in the amygdala or hippocampus. These results show
      that stimuli associated with predatory threat come to activate similar brain
      regions to the threat stimulus itself.

PMID- 16111752
TI  - HLA genes in Mexican Teeneks: HLA genetic relationship with other worldwide
      populations.
AB  - The HLA allele frequency distribution of the Mexican Teenek Indians has been
      studied and compared with those of other First American Natives and worldwide
      populations (a total of 15694 chromosomes from 73 different populations were
      analyzed). This study corroborate the restricted HLA polymorphism in the
      Amerindian populations and demonstrate how the Amerindians show a relatively
      homogeneity as opposed to other First Native American groups. Finally, the
      present data support previous ones that state the lack of complete correlation
      between language and genetics in micro-environmental studies; Teenek Mayan
      language does not correspond with a close Mayan (Guatemala) relatedness.

PMID- 16111753
TI  - Molecular cloning and characterization of Fc-TSP from the Chinese shrimp
      Fennerpenaeus chinensis.
AB  - Thrombospondins (TSPs) are extracellular, multidomain, calcium-binding
      glycoproteins that modulate cell behavior in homeostasis and during development,
      wound-healing, immune response and tumor growth of adult tissues in vertebrates.
      In invertebrates these proteins are a major component of cortical rods in mature
      oocytes. A fragment of a thrombospondin-like gene was generated by screening a
      subtractive cDNA library constructed from the hemocytes of Chinese shrimp,
      Fennerpenaeus chinensis. The full length F. chinensis cDNA of thrombospondin was
      cloned by 3'- and 5'-rapid amplification of cDNA ends (3'- and 5'-RACE). The
      complete cDNA sequence, named Fc-TSP, is 2886 bp and the open reading frame of
      the cDNA encodes a 938-residue protein that contains three ChtBD2 domains, an EGF
      domain, a TSP-3 domain and a common TSP-C (CTD) domain. The protein shares a high
      sequence identity with the mj-TSPa (46.3%), mj-TSPb (46.9%) and mj-TSPc (51.9%)
      of Marsupenaeus japonicus. The expression and distribution of Fc-TSP in both
      challenged and unchallenged shrimps were studied by Northern blot, RT-PCR and in
      situ hybridization. Northern blot analysis showed that the Fc-TSP transcripts
      were detected in the hemocytes, heart, intestine, stomach and ovary of both
      challenged and unchallenged shrimps, but the signal was much stronger in the
      challenged tissues. A strong hybridization signal was detected only in challenged
      hepatopancreas, with no signal in the unchallenged tissue. The RT-PCR showed that
      the Fc-TSP was detected in both challenged and unchallenged tissues including the
      hemocytes, heart, hepatopancreas, stomach, gills, intestine, spermary and ovary.
      Except for the ovary and spermary, the signal of challenged tissues was
      relatively stronger than that of unchallenged ones, especially in hepatopancreas.
      These results suggest that the thrombospondin was upregulated in the hemocytes,
      heart, intestine and stomach of challenged shrimp, and induced in the
      hepatopancreas of challenged shrimps. Therefore, Fc-TSP may be involved in the
      defense responses of the shrimp.

PMID- 16111754
TI  - The ophthalmic clinical evaluation exercise: reliability determination.
AB  - PURPOSE: Reliable and valid tools must be developed to assess the core residency
      competencies identified by the Accreditation Council for Graduate Medical
      Education. The Ophthalmic Clinical Evaluation Exercise (OCEX) is a tool designed
      to assess the ophthalmology resident's competence in patient care. The OCEX has
      been shown to have face and content validity. This study will determine the
      degree to which the OCEX is reliable and has construct validity. PARTICIPANTS:
      Ninety-four academic ophthalmology teaching faculty from ophthalmology residency
      programs across the country. METHODS: Participants reviewed a video compact disc
      of the same resident and new patient encounter and then completed the OCEX. A
      scoring rubric was provided. RESULTS: Results indicate that the OCEX is a
      reliable tool for faculty to use to assess residency competency. The coefficient
      alpha statistic (a measure of reliability/internal consistency) for the OCEX as a
      whole was 0.81. The alpha statistics for 3 of 4 subscales that comprise the OCEX
      (i.e., interviewing skills = 0.65, interpersonal skills/professionalism = 0.73,
      case presentation = 0.70) were lower than the OCEX as a whole, but were
      acceptable for new scales. However, the alpha for the examination subscale (i.e.,
      0.27) was extremely low. Interrater reliability assessment shows that of 33
      individual OCEX items, 31 (94%) had at least 85% of the raters rating the student
      in 1 of 2 consecutive rating categories. CONCLUSIONS: The OCEX shows both
      reliability and validity and, therefore, meets the Accreditation Council for
      Graduate Medical Education criteria for an acceptable assessment tool.

PMID- 16111755
TI  - Refractive error in urban and rural adult Chinese in Beijing.
AB  - PURPOSE: To evaluate refractive error and its demographic associations in an
      urban and rural population in northern China. DESIGN: Epidemiological study.
      PARTICIPANTS: The Beijing Eye Study is a population-based cohort study in
      northern China including 4439 subjects. Excluding pseudophakic and aphakic
      patients, the present study involved 4319 subjects. It was divided into a rural
      part (1905 [44.1%] subjects) and an urban part (2414 [55.9%] subjects). Mean age
      was 55.85+/-10.33 years (range, 40-90). METHODS: Standardized ophthalmologic
      examination. For statistical analysis, the spherical equivalent was converted to
      binary variables, and logistic regression was used to investigate the association
      with continuous or categorical independent variables. MAIN OUTCOME MEASURE:
      Refractive error. RESULTS: Mean refractive error measured -0.33+/-2.22 diopters
      (D) (range, -20.88 to +7.88). Myopia of >-0.50 D, -1.0 D, >-6.0 D, and >-8 D,
      respectively, occurred in 22.9% (95% confidence interval [CI], 21.7-24.2), 16.9%
      (95% CI, 15.8-18.0), 2.6% (95% CI, 2.2-3.1), and 1.5% (95% CI, 1.1-1.9) of the
      subjects, respectively. Myopic refractive error was associated significantly with
      younger age (P<0.001), urban region (vs. rural region) (P<0.001), higher
      educational background (P<0.001), higher degree of nuclear cataract (P<0.001),
      decreasing uncorrected visual acuity (UCVA) (P<0.001), decreasing best-corrected
      visual acuity (BCVA) (P<0.001), and female gender (P<0.001). Prevalence of high
      myopia (myopic refractive error >-8 D) was associated with age (P<0.001), female
      gender (P = 0.020), urban region (P = 0.023), and lower BCVA (P<0.001). Mean
      anisometropia was 1.09+/-2.03 D (median, 0.38; range, 0-22.0). Prevalence of
      anisometropia of > or =1 D was associated significantly with age (P<0.001),
      refractive error (P<0.001), BCVA (P<0.001), and region (P<0.001). Mean astigmatic
      error measured 0.62+/-0.90 D (median, 0.25; range, 0-7.50). Astigmatism of > or
      =1 D was associated significantly with age (P<0.001), lower UCVA (P = 0.003),
      lower BCVA (P<0.001), urban area (P<0.001), and degree of cortical cataract (P =
      0.027). CONCLUSIONS: As in other population-based studies on Chinese, myopia was
      more prevalent in younger subjects. Myopia was associated with urban region,
      educational background, female gender, decreasing visual acuity, and nuclear
      cataract. If longitudinal studies confirm the association of refractive error
      with age, refractive surgery may achieve emmetropia only for a limited time.

PMID- 16111756
TI  - Intraoperative management of partial flap during LASIK: a small case series
      report.
AB  - PURPOSE: To report the intraoperative management of incomplete microkeratome
      LASIK flaps. DESIGN: Small, retrospective, noncomparative, interventional case
      series. PARTICIPANTS: Five outpatients. METHODS: In 5 eyes of 5 patients, the
      premature stop of the microkeratome resulting from mechanical obstacles resulted
      in an incomplete flap that would not allow for the completion of the LASIK
      procedure. After the careful realignment of the partial flaps and the removal of
      the identified obstacles, the second pass of the microkeratome resulted in flaps
      of the intended size. MAIN OUTCOME MEASURES: Final creation of a flap as
      intended, completion of the procedure, and visual and refractive outcome of the
      operative eyes. RESULTS: The second pass of the microkeratome resulted in flaps
      as planned. All the procedures were completed, and the operative eyes that were
      followed up for at least 3 months had excellent visual and refractive results.
      CONCLUSIONS: The second pass of the microkeratome can successfully manage
      incomplete flaps resulting from microkeratome premature stop as a result of
      mechanical obstacles.

PMID- 16111757
TI  - Vascular response of the bulbar conjunctiva to diabetes and elevated blood
      pressure.
AB  - OBJECTIVE: Retinovascular changes associated with diabetes have been clearly
      documented; changes in vessels of the conjunctiva are less well described. We
      examined changes in conjunctival vessel morphologic features in participants with
      and without diabetes. DESIGN: Case-control study. PARTICIPANTS AND CONTROLS:
      Fifty-three patients with diabetes (17 with type 1 diabetes, 36 with type 2
      diabetes) and 60 controls (all aged 20-94 years). METHODS: Digital red-free
      conjunctival images were captured and an automated computer algorithm was used to
      derive indices that describe the morphologic features of vessels of the
      conjunctiva. Percentage differences in vessel indices were adjusted for age,
      gender, blood pressure, and smoking status. MAIN OUTCOME MEASURES: Mean vessel
      diameter (micrometers) and vessel density (square millimeters of vessel per
      square centimeter of bulbar conjunctiva). RESULTS: A strong positive association
      between the duration of diabetes and overall mean vessel width was observed
      (P<0.001), resulting from changes in larger vessels (>80 mum in width).
      Conversely, the duration of diabetes showed a strong inverse association with
      vessel area (P<0.001) that appeared to be driven by the trend observed in smaller
      vessels (<40 mum in width). A 25% reduction (95% confidence interval [CI], -35%
      to -13%; P<0.001) in vessel density in those with type 1 diabetes and a 14%
      reduction (95% CI, -24% to -3%; P = 0.016) in those with type 2 diabetes,
      compared with controls, was observed. Mean vessel widths were 11% (95% CI, 4%
      17%; P = 0.001) wider in type 1 and 5% (95% CI, 0%-10%; P = 0.073) wider in those
      with type 2 diabetes compared with controls. The difference in magnitude of
      effect for type 1 and type 2 diabetes compared with controls was explained by
      duration of diabetes. Grade of diabetic retinopathy and elevated blood pressure
      showed similar but less strong associations with vessel indices. CONCLUSIONS:
      Loss of capillaries and macrovessel dilation in the conjunctiva associated with
      diabetes compares with well-known vessel changes in the retina. Associations
      between morphologic changes in the conjunctiva and elevated blood pressure were
      similar but less strong; this may show that diabetic angiopathy predominates in
      those with both diabetes and elevated blood pressure.

PMID- 16111758
TI  - The Tajimi Study report 2: prevalence of primary angle closure and secondary
      glaucoma in a Japanese population.
AB  - PURPOSE: To determine the prevalence of primary angle-closure glaucoma (PACG),
      secondary glaucoma (SG), and all glaucoma in a Japanese population as a part of
      the Tajimi Study. DESIGN: Population-based epidemiological survey. PARTICIPANTS:
      A random sample of residents 40 years or older from Tajimi, Japan. INTERVENTION:
      Each subject underwent a screening program comprising an interview and an
      ophthalmic examination, including Goldmann applanation tonometry, slit-lamp
      examination, a van Herick test, fundus photography, and a screening visual field
      (VF) test using frequency-doubling technology. If glaucoma was suspected, the
      subject was referred for a definitive examination that included slit-lamp
      examination, gonioscopy, intraocular pressure measurement, a VF test, and optic
      disc and fundus examination. A diagnosis of PACG or SG was made based on slit
      lamp examination, gonioscopy, optic disc appearance, and perimetric results. MAIN
      OUTCOME MEASURES: Prevalences of PACG, SG, and all cases of glaucoma. RESULTS: Of
      3870 eligible people, 3021 (78.1%) participated in the study. Estimated
      prevalences of PACG and SG in those over 40 years were 0.6% (95% confidence
      interval [CI], 0.4%-0.9%) and 0.5% (95% CI, 0.2%-0.7%), respectively. Prevalences
      of all glaucoma and glaucoma/suspected glaucoma were estimated to be 5.0% (95%
      CI, 4.2%-5.8%) and 7.5% (95% CI, 6.5%-8.4%), respectively. CONCLUSIONS:
      Prevalences were 0.6%, 0.5%, and 5.0%, respectively, for PACG, SG, and all
      glaucoma in subjects over 40 years from Tajimi, Japan.

PMID- 16111759
TI  - Pneumatic retinopexy for inferior retinal breaks.
AB  - PURPOSE: To introduce a pneumatic retinopexy positioning for the management of
      retinal detachment from inferior retinal breaks after failed scleral buckle.
      DESIGN: Retrospective review of interventional consecutive case series.
      PARTICIPANTS: Seventeen eyes of 17 patients followed up from January 1993 to
      February 2005. INTERVENTION: Internal tamponade was achieved by 10 degrees
      Trendelenburg positioning, 10 degrees neck hyperextension, 10 degrees ocular
      supraduction and a large intravitreal gas bubble. MAIN OUTCOME MEASURES: Visual
      acuity, intraocular pressure, and retinal flattening were evaluated. RESULTS: All
      patients tolerated the procedure. Retinal reattachment was maintained in 15 of 17
      patients (88.2%) followed up for a mean of 2.8 years (range, 0.1-11.5 years). Two
      patients experienced redetachment after 5 days and 4 months respectively. Six
      patients required antiglaucoma medications during the technique. CONCLUSIONS:
      Graduated body-neck-eye tilt allowed retinal reattachment in most eyes with
      inferior retinal detachment after failed scleral buckle.

PMID- 16111760
TI  - Synthesis, spectroscopy and antiproliferative activity of cis- and trans
      platinum(II) complexes with diethyl (pyridin-4-ylmethyl)phosphate. X-ray crystal
      structure of trans-Pt(II) complex.
AB  - Preparations of cis- and trans-platinum(II) complexes of diethyl (pyridin-4
      ylmethyl)phosphate (4-pmOpe) have been described. These complexes were identified
      and characterized by far-IR, 1H NMR, 13C NMR, 31P NMR and 195Pt NMR and
      microanalyses. The crystal and molecular structure of trans-platinum(II) complex
      i.e., trans-[PtCl2(4-pmOpe)2] was determined by the X-ray diffraction. Novel
      complexes were assayed for their potential antiproliferative effect against HT 29
      (colorectal adenocarcinoma) and A 549 (non-small cell lung cancer) cell lines as
      well as normal human peripheral blood lymphocytes. The results obtained indicate
      that novel analogues of cis-diamminedichloroplatinum(II) cause inhibition of
      cells growth which suggest that they could be chemotherapeutic drugs in the
      future.

PMID- 16111761
TI  - GPCR modulation by RAMPs.
AB  - Our conceptual understanding of the molecular architecture of G-protein coupled
      receptors (GPCRs) has transformed over the last decade. Once considered as
      largely independent functional units (aside from their interaction with the G
      protein itself), it is now clear that a single GPCR is but part of a multifaceted
      signaling complex, each component providing an additional layer of
      sophistication. Receptor activity-modifying proteins (RAMPs) provide a notable
      example of proteins that interact with GPCRs to modify their function. They act
      as pharmacological switches, modifying GPCR pharmacology for a particular subset
      of receptors. However, there is accumulating evidence that these ubiquitous
      proteins have a broader role, regulating signaling and receptor trafficking. This
      article aims to provide the reader with a comprehensive appraisal of RAMP
      literature and perhaps some insight into the impact that their discovery has had
      on those who study GPCRs.

PMID- 16111762
TI  - A nonparametric approach to extract information from interspike interval data.
AB  - In this work we develop an approach to extracting information from neural spike
      trains. Using the expectation-maximization (EM) algorithm, interspike interval
      data from experiments and simulations are fitted by mixtures of distributions,
      including Gamma, inverse Gaussian, log-normal, and the distribution of the
      interspike intervals of the leaky integrate-and-fire model. In terms of the
      Kolmogorov-Smirnov test for goodness-of-fit, our approach is proved successful
      (P>0.05) in fitting benchmark data for which a classical parametric approach has
      been shown to fail before. In addition, we present a novel method to fit mixture
      models to censored data, and discuss two examples of the application of such a
      method, which correspond to the case of multiple-trial and multielectrode array
      data. A MATLAB implementation of the algorithm is available for download from .

PMID- 16111763
TI  - A novel polyclonal antibody specific for the Na(v)1.5 voltage-gated Na(+) channel
      'neonatal' splice form.
AB  - Voltage-gated Na(+) channel (VGSC) diversity is achieved through a number of
      mechanisms: multiple subunits, multiple genes encoding the pore-forming VGSC
      alpha-subunit and multiple gene isoforms generated by alternative splicing. A
      major type of VGSCalpha alternative splicing is in D1:S3, which has been proposed
      to be developmentally regulated. We recently reported a D1:S3 spliced form of
      Na(v)1.5 in human metastatic breast cancer cells. This novel 'neonatal' isoform
      differs from the counterpart 'adult' form at seven amino acids (in the
      extracellular loop between S3-S4 of D1). Here, we generated an anti-peptide
      polyclonal antibody, named NESOpAb, which specifically recognised 'neonatal' but
      not 'adult' Na(v)1.5 when tested on cells specifically over-expressing one or
      other of these Na(v)1.5 spliced forms. The antibody was used to investigate
      developmental expression of 'neonatal' Na(v)1.5 (nNa(v)1.5) in a range of mouse
      tissues by immunohistochemistry. Overall, the results were consistent with
      nNa(v)1.5 protein being more abundantly expressed in selected tissues
      (particularly heart and brain) from neonate as compared to adult animals.
      Importantly, NESOpAb blocked functional nNa(v)1.5 ion conductance when applied
      extracellularly at concentrations as low as 0.05 ng/ml. Possible biological and
      clinical applications of NESOpAb are discussed.

PMID- 16111764
TI  - Evolution of the human fear-circuitry and acute sociogenic pseudoneurological
      symptoms: the Neolithic balanced-polymorphism hypothesis.
AB  - In light of the increasing threat of large-scale massacres such as terrorism
      against non-combatants (civilians), more attention is warranted not only to
      posttraumatic stress disorder (PTSD) but also to acute sociogenic
      pseudoneurological ("conversion") symptoms, especially epidemic sociogenic
      symptoms. We posit that conversion disorders are etiologically related to
      specific evolutionary pressures (inescapable threats to life) in the late stage
      of the human environment of evolutionary adaptedness (EEA). Bracha et al. have
      recently argued that from the neuroevolutionary perspective, medically
      unexplained efferent vasovagal syncope and medically unexplained craniofacial
      musculoskeletal pain in young otherwise healthy individuals, may be taxonomized
      as stress and fear-circuitry disorders. In the present article, we extend
      neuroevolutionary perspectives to acute pseudoneurological sociogenic
      ("conversive") symptoms: psychogenic non-epileptic attacks ("pseudoseizures"),
      epidemic sociogenic disorders (DSM-IV-TR Epidemic "Hysteria"), conversive motor
      deficits (pseudo-paralysis and pseudo-cerebellar symptoms), and psychogenic
      blindness. We hypothesize that these perplexing pseudoneurological stress
      triggered symptoms, which constitute psychopathology in extant humans, are
      traceable to allele-variant polymorphisms which spread during the Neolithic EEA.
      During Neolithic warfare, conversive symptoms may have increased the survival
      odds for some non-combatants by visually (i.e., "non-verbally") signaling to
      predatory conspecifics that one does not present a danger. This is consistent
      with the age and sex pattern of conversive disorders. Testable and falsifiable
      predictions are presented; e.g., at the genome-transcriptome interface, one of
      the major oligogenic loci involved in conversive spectrum disorders may carry a
      developmentally sensitive allele in a stable polymorphism (balanced polymorphism)
      in which the gene expression mechanism is gradually suppressed by pleiotropic
      androgens especially dehydroxyepiandrosterone sulfate (DHEA-S). Taxonomic
      implications for the much-needed rapprochement between the forthcoming Diagnostic
      and Statistical Manual for Mental Disorders, Fifth Edition (DSM-V) and the
      International Classification of Diseases (ICD) are discussed.

PMID- 16111765
TI  - Great expectations: factors influencing patient expectations and doctors
      recommendations at a Mood Disorders Unit.
AB  - BACKGROUND: Literature about expectations and management of depression within
      community samples reflects attitudes of people who have generally not received
      treatment. We examined the factors influencing treatment expectations and
      psychiatrists' treatment recommendations for patients referred to a mood
      disorders unit with identified episodes of major depression. METHODS: Prior to
      attending a mood disorders unit, 182 men and women who met DSM-III-R or DSM-IV
      criteria for current major depression provided data on sociodemographic details,
      history of medical and psychiatric illness and expectations of treatment.
      Psychiatrists' treatment recommendations to the referring clinician were assessed
      to determine whether the patients' initial expectations were met. RESULTS: Data
      analyses revealed three factors relating to patients' expectations: "enhanced
      coping", "providing fresh ideas for the referring doctor" and "providing fresh
      ideas to self". Patients' expectations were influenced by sociodemographic and
      illness-related characteristics. In particular, young female patients typically
      expected to receive strategies to enhance coping, while those with lifetime
      anxiety expected less active involvement on their part. Some clinicians'
      recommendations were dependent upon depression type and patient factors. Women
      and those with a history of anxiety disorders received more education and
      recommendations for relationship counselling and support groups. LIMITATIONS: The
      study design did not allow determination of the impact of patients' expectations
      on the psychiatrists' recommendations. CONCLUSIONS: Individual and illness
      characteristics are important predictors of treatment expectations prior to
      specialist care. It appears that doctors take these factors into account with
      implications for patients' satisfaction with the type of care recommended.

PMID- 16111766
TI  - Tissue microcircumstances for leukocytic infiltration into the testis and
      epididymis in mice.
AB  - Spermatozoa do not appear in the seminiferous epithelium until puberty, when
      immune tolerance has already been established. Therefore, they contain various
      autoimmunogenic materials which are recognized as foreign by the self immune
      system. However, the testis and epididymis are known as immunologically
      privileged organs. In particular, the blood-testis barrier (BTB) formed by
      Sertoli cells and the blood-epididymal barrier formed by epididymal epithelial
      cells protect autoimmunogeneic spermatozoa from attack by the self immune system.
      The immune privileged circumstances in the testis and epididymis have been
      demonstrated by many studies to involve a local transplantation system. We review
      here the immune privileged status of these organs from the viewpoint of induction
      of inflammatory cell responses in mice. The testicular interstitium in mice is
      resistant to vasculitis, lymphangitis, spermatic granuloma and polymorphonuclear
      cell infiltration: however, the epididymal interstitium is vulnerable to them.
      Therefore, the testicular tissue outside BTB is also protected from inflammatory
      cell infiltration, although many resident macrophages are normally present in the
      testis. In sharp contrast, subcutaneous injection of viable syngeneic testicular
      germ cells (TGC) alone induces autoimmune orchitis with no involvement of the
      epididymitis in mice. In the testes of TGC-immunized animals, severe lymphocytic
      infiltration with aspermatogenesis was seen in spite of no use of adjuvants.
      Unexpectedly, injections of viable epididymal spermatozoa (ES) did not evoke any
      autoimmune inflammation in the epididymides. Therefore, the testis rather than
      the epididymis may easily become an unprivileged organ as to autoimmunity under
      some special conditions.

PMID- 16111767
TI  - Current concepts of tumor-infiltrating lymphocytes in human malignancies.
AB  - Tumor-infiltrating lymphocytes (TILs) develop as manifestations of the
      recognition and defense against malignant cells by the host immune system. TILs
      were literally defined as "tumor-infiltrating lymphocytes", which a posteriori
      locate within the tumor tissues. Although such cells can be found, they fail to
      control the growth of tumor. Many have proposed diverse mechanisms for
      dysfunction of TILs with regard to the roles of immunosurveillance against
      cancer. However, only a few cancer types, e.g. melanoma, have seen the benefits
      brought by activating these cells for immunotherapy. Functional defects of TILs
      have been linked to abnormalities of signaling molecules; however, there is
      conflicting data. The death of TILs was attributed to expression of cancer
      derived FasL, PD-1 and RCAS1, and cancer-induced activation-induced cell death
      (AICD). Confirmed by studies using TILs and animal models, the compromise of
      tumor-specific immune responses was thought to result from not only mechanisms of
      clonal anergy but also exhaustion and/or deletion. Furthermore, functional
      cytotoxic CD8(+) TILs might be rendered incompetent by cancer-induced up
      regulation of inhibitory NK receptors or proximal signaling abnormalities.
      Additionally, immune privilege was partly attributed to recruitment of regulatory
      T cells to the tumor sites. The failure of IL-2 signaling, which stands at the
      center of T cell functionalities, had been linked to the enzymatic activity of
      cancer-derived matrix metalloproteinases (MMPs). Finally, the exploitation of IDO
      expression, an important enzyme in pregnancy-related immunosuppression, by cancer
      cells might play a role in tumor immunity. The disparity of cancer types, origin,
      developmental stages and individual genetic backgrounds likely account for
      differences, or even contradictions, which might be the reason why immunotherapy
      works only on a few cancer types. Delineating the mechanisms behind functional
      defects of TILs can help not only boost chances of the development of a
      successful cure but understand the not fully identified roles played by immune
      system in the face of malignancies.

PMID- 16111768
TI  - In vivo gene transfer into the mouse uterus: a powerful tool for investigating
      implantation physiology.
AB  - In vivo transient transfection of cDNA into uterine endometrium during the
      implantation period provides great opportunities to analyse the
      physiology/pathophysiology of implantation at the molecular level. We review here
      methodologies which have been applied for this purpose. Viral vectors are widely
      used for in vivo gene therapy models; however, there is no successful example of
      gene transfer into the uterus using such vectors. Cationic liposome-based
      technologies have produced some successful results, causing alterations in
      implantation physiology. We applied a haemagglutinating virus of Japan envelope
      (HVJ-E) vector system and showed that the transfection efficiency was much higher
      than that of methods based on cationic liposome. Commercial HVJ-E vector
      (GenomONE-Neo) is now also available. Several successful examples of in vivo gene
      transfer revealed that calcitonin, Hoxa 10 and NF kappaB play important roles in
      determining the efficiency or timing of implantation. Based on this knowledge, we
      should further analyse the pathophysiology of human implantation failure using
      human materials.

PMID- 16111769
TI  - Eye tracking in schizophrenia: does the antisaccade task measure anything that
      the smooth pursuit task does not?
AB  - Smooth pursuit and antisaccade eye-tracking abnormalities have been proposed as
      endophenotypes for schizophrenia. However, it is not clear whether these tasks
      measure the same underlying abnormality. We hypothesised that these measures
      would be correlated. The association between smooth pursuit and antisaccade task
      performance was assessed in 50 schizophrenic patients, 80 unaffected first-degree
      relatives and 40 unaffected controls. Smooth pursuit measures included gain,
      number of saccades and a qualitative measure of smooth pursuit. The antisaccade
      distractibility error (ADE) score was the only measure of the antisaccade task. A
      significant correlation was found between reduced gain and an increased ADE score
      for all the subjects in the three groups combined. The total number of saccades
      was negatively correlated with the ADE score in the schizophrenic group, but
      positively in the relative group. Qualitative ratings of smooth pursuit
      correlated with the ADE score. Our results suggest that the antisaccade
      distractibility error score is related to gain and qualitative measures of smooth
      pursuit, although the relationship with number of saccades did not conform to
      this pattern. The finding may reflect a shared genetic liability, that affects
      both eye-tracking phenotypes. It is likely that both measures reflect frontal
      cortical dysfunction.

PMID- 16111770
TI  - Lymphocytes from one side of the bovine mammary gland migrate to the contra
      lateral gland and lymph node tissue.
AB  - The four quarters of bovine mammary glands are completely separated and two
      quarters on each side (right or left) are connected to ipsi lateral supra mammary
      lymph nodes. It is not clear whether cells infused into the cistern of the
      mammary gland are capable of migrating to lymph nodes or the general circulation.
      To examine cell migration, a prescapular lymph node was removed from each of two
      lactating and three non-lactating dairy cows, and isolated lymphocytes were
      stained with Hoechst 33342. Autologous stained cells were infused into the
      mammary gland and then activated by intramammary infusion of zymosan-stimulated
      serum (source of C5a). After 17 h, Escherichia coli J5 bacterin was infused into
      the contra lateral mammary gland to mimic infection. After 43 h cows were
      euthanized and tissue samples (mammary quarters, right and left supra mammary,
      mesenteric, ileocecal and prescapular lymph nodes, liver and spleen) were
      collected for microscopic examination as well as flow cytometric analysis.
      Hoechst stained cells were detected not only in infused quarters, but also in
      contra lateral quarters as well as in both supra mammary lymph nodes. This
      indicates that cells infused into the mammary gland migrate to contra lateral
      tissues and supra mammary lymph nodes.

PMID- 16111771
TI  - Desensitization of mast cells' secretory response to an immuno-receptor stimulus.
AB  - Knowledge of the desensitization process of responses to the type I receptor for
      IgE (FcepsilonRI) is rather limited. We investigated whether mast cells'
      secretory response to this receptor's stimulus can be subjected to
      desensitization under protocols usually employed for hormonal or neural
      receptors, i.e. by excessive, prolonged or repetitive exposure to the stimulus.
      To study this we have employed the rat mucosal-type mast cells of the RBL-2H3
      line, which enables a rigorous examination of the response to the FcepsilonRI
      stimulus. These cells exhibited a marked decrease of both, secretion of granule
      stored and de novo synthesized mediators to an optimal stimulation, when first
      exposed to prolonged FcepsilonRI-IgE clustering by specific antigen (DNP(11)-BSA)
      or by the IgE specific mAb 95.3 at concentrations that are below the threshold of
      inducing secretion. The extent of desensitization depended on the employed
      concentrations of IgE and on the clustering agents, as well as on the length of
      the desensitization period. The levels of cell surface FcepsilonRI expression and
      of cell-bound IgE were determined following the desensitization period and no
      significant correlation has been observed between the extent of endocytosis and
      the observed desensitization. Thus, a different process, which interferes with
      FcepsilonRI stimulus-response coupling network, is responsible for the observed
      desensitization.

PMID- 16111773
TI  - Early extubation following major tracheal surgery in select children.
AB  - Major airway surgery in children has traditionally consisted of a period of
      endotracheal intubation after the procedure for a period of 1-2 weeks to ensure
      stability of the repair. Recent literature has supported a trend toward
      decreasing this time period to prevent the consequences of leaving a foreign body
      in the airway and the morbidity associated with the use of sedation and narcotics
      in children. We present a series of five select children from our institution
      that underwent major tracheal surgery and were successfully extubated early in
      their postoperative course; four on postoperative day number 1. This demonstrates
      the feasibility of this approach in select patients.

PMID- 16111772
TI  - HLA-DRB5*0101 and -DRB1*1501 expression in the multiple sclerosis-associated HLA
      DR15 haplotype.
AB  - The HLA region, and particularly the DR15 haplotype (containing the two DRB*
      genes DRB1*1501 and DRB5*0101 and the tightly linked DQ alleles DQA*0102 and
      DQB1*0602, which together form the DQw6 molecule) in Caucasians, shows the
      strongest genetic association with multiple sclerosis (MS). In the DR15
      haplotype, two beta-chains HLA-DRB1*1501 and -DRB5*0101 are co-expressed
      resulting in two different surface HLA-DR alphabeta heterodimers, DR2b and DR2a.
      Most previous studies focused on DRB1*1501, however, both DR2a and DR2b may
      contribute to MS pathogenesis via antigen presentation to myelin-specific T
      lymphocytes. We therefore analyzed the expression of the two DR15 genes in
      various antigen presenting cells (APCs), central nervous system and thymic
      tissues. Transcript levels were higher for DRB5*0101 in all cell types and
      tissues. Both HLA-DR heterodimers were expressed at significant levels on the
      cell surface, where they showed a differential expression pattern in different
      APCs. They were similarly regulated after stimulation with interferon-gamma and
      interleukin-4. Finally, immunohistochemistry experiments indicated that both
      molecules were expressed in thymic tissue. Our results encourage future research
      to investigate the potential functional relevance of both genes for the
      pathogenesis of MS.

PMID- 16111774
TI  - A new recombinant virus system for the study of HIV-1 entry and inhibition.
AB  - The construction is described of a HIV-1 proviral, eGFP-tagged plasmid that
      allows for the recombination of any selected env gene without the use of
      restriction enzymes and for the quantitation of the infection by the recombinant
      virus using flow cytometry. The system was tested showing that an isoleucine to
      valine substitution at residue position 37 of the HIV-1 gp41 impairs the fitness
      of the virus but does not lead by itself to T-20 resistance.

PMID- 16111775
TI  - Effects of paradoxical sleep deprivation on the performance of rats in a model of
      visual attention.
AB  - In the present work we sought to evaluate the effects of paradoxical sleep
      deprivation (PSD) on the performance of rats in the five-choice serial reaction
      time task, a test designed to assess attentional function. Adult male Wistar rats
      were trained to detect a brief (1 s) light stimulus randomly presented in one of
      five locations in a box specially designed for the task. After achieving stable
      performance, the animals were submitted to 96 h of sleep deprivation by the
      platform technique, in which the rats are placed on top of small platforms in a
      tank filled with water. During sleep, particularly during the paradoxical stage,
      the loss of muscle tone make the animals fall into the water, thus awakening them
      and so depriving of sleep. Performance in the task was assessed daily during the
      96 h deprivation period and also during seven recovery days afterwards.
      Paradoxical sleep deprivation reduced accuracy on the on the third (72 h) and
      fourth (96 h) days of sleep deprivation compared to home-cage controls, and this
      impairment reverted soon after the beginning of the recovery period. Sleep
      deprived animals also showed an increase in omissions in the first day of PSD and
      a reduction on the number of trials started on the fourth day of sleep
      deprivation. No significant group differences were observed in premature and
      perseverative responses, correct response latency and reward latency. Our results
      thus indicate that paradoxical sleep deprivation impairs attentional function.

PMID- 16111776
TI  - Induction of heat shock proteins (hsp70) in the zebra mussel (Dreissena
      polymorpha) following exposure to platinum group metals (platinum, palladium and
      rhodium): comparison with lead and cadmium exposures.
AB  - An increasing number of papers concentrate on the availability and uptake of
      platinum group elements (PGE) by different organisms. These metals are discharged
      into the environment from different anthropogenic sources, such as automobile
      catalytic converters, hospitals and other medical institutions. As the effects of
      these precious metals on organisms remain unclear, the induction of heat shock
      proteins (hsp70) in zebra mussels (Dreissena polymorpha) following exposure to
      soluble salts of platinum, palladium and rhodium was compared with the hsp70
      induction in mussels following exposure to cadmium and lead. Mussels were sampled
      weekly during a period of 10 weeks and analyzed for their metal concentration and
      their hsp70 level. Highest metal uptake was found for Cd, followed by Pt, Pb and
      Pd. Rh demonstrated the lowest uptake rate. A clear time-dependent increase of
      hsp70 levels occurred in all exposed mussels. Concentrations of hsp70 started to
      rise between days 18 and 25, except for the Pt-exposed group, where the initial
      increase was between days 25 and 32. All groups reached maximal hsp70
      concentrations at day 39. Subsequently, hsp70 levels decreased to initial levels
      for the remaining exposure period. Threshold metal levels for the hsp70 induction
      varied among the metals and increased in the order: Rh<Pd< or =Pb<Pt<Cd. Highest
      hsp70 values were found for mussels exposed to Pd, with a 25-fold higher level
      than in the controls, followed by Pt- and Rh-exposed mussels, which showed a 19
      fold increase. The hsp70 levels of the mussels exposed to Cd and Pb were much
      lower, showing 6- and 12-fold higher values than the control, respectively. The
      clear induction of hsp70 due to exposure to Pt, Pd and Rh gives evidence for
      strong cellular effects of these metals, especially, when compared with lead and
      cadmium. Among the metals tested, Pd seems to have the highest potential as
      inducer for hsp70 production due to its low threshold level in combination with
      the strongest effect.

PMID- 16111777
TI  - Whole-heart coronary magnetic resonance angiography in a patient with unstable
      angina.

PMID- 16111778
TI  - Effect of pathogen-specific clinical mastitis on herd life in two New York State
      dairy herds.
AB  - The objective of this study was to estimate the effects of clinical mastitis (CM)
      (both with and without specific pathogen identification) occurring in different
      stages of lactation on length of herd life in two New York State dairy farms. The
      2,697 cows in the study were followed for one lactation (the first-occurring one
      on or after 1 October 1999), until it ended because of a new lactation, culling,
      or end of study (31 March 2001 in one farm; 31 July 2001 in the other). A Cox
      proportional hazards model with time-dependent covariates, in SAS((R)), was used
      to measure, within a lactation, the effect of the first occurrence of CM (without
      specific pathogen identification) occurring 1--7, 8--66, 67--100, 101--225, or
      >or=226 days in milk (DIM), on how long cows remained in the herd. For the first
      occurrence of CM due to Streptococcus spp., Staphylococcus aureus, Staphylococcus
      spp., Escherichia coli, Klebsiella spp., and 'no pathogen isolated', the
      intervals were before and after the median DIM of first occurrence of each
      pathogen. There were too few cases due to Arcanobacterium pyogenes, and 'other
      pathogens grouped together' to split into intervals, so they were modeled as
      binary variables, i.e. as they occurred. CM was modeled using time-dependent
      covariates, to account for its differing effects throughout lactation on culling.
      Other variables controlled for were herd, parity, calving season, and other
      significant diseases. In the dataset, the lactational incidence risk of the first
      occurrence of CM was 18.2%; 20.0% of the cows did not survive the lactation that
      was studied. The overall annual culling percentage for both herds during the
      study period (including all cows, whether eligible for the study or not) was
      35.6%. For cows with CM without pathogen identification, their highest hazard
      ratio (HR) of culling occurred from 67 to 100 DIM. All of the pathogens modeled
      markedly reduced herd life. On average over the entire lactation, cows with
      Staphylococcus spp. CM had the highest HRs for culling, although there were no
      significant differences among pathogens (at p=0.0018 (reflecting 28 pairwise
      comparisons)). For early-occurring (before median DIM of first occurrence) S.
      aureus CM, the daily rate of change of the HR of culling increased over time. The
      HRs for culling were particularly high for late-occurring (after median DIM of
      first occurrence) E. coli and Klebsiella spp. CM early in the interval, but the
      daily rate of change of the hazard of culling for these two pathogens decreased
      sharply over time. Treating CM as time-dependent therefore allowed us to measure
      in greater detail, its varying effects (of when it occurred) on herd life.

PMID- 16111779
TI  - Purification and characterization of a furfural reductase (FFR) from Escherichia
      coli strain LYO1--an enzyme important in the detoxification of furfural during
      ethanol production.
AB  - Furfural, an inhibitor of ethanol production from hemicellulose acid
      hydrolysates, is reductively detoxified to furfuryl alcohol by the ethanologenic
      bacterium Escherichia coli strain LYO1. Furfural reductase was purified 106-fold
      from this bacterium to approximately 50% homogeneity. It has a native molecular
      mass of 135 kDa, determined by gel filtration, and subunit molecular mass of
      approximately 68 kDa, determined by denaturing gel electrophoresis, indicating
      the holoenzyme is a dimer of two similar if not identical subunits. The enzyme
      shows strong activity from pH 4 to 8 (optimum pH 7.0), relatively high
      temperature tolerance (50-55 degrees C), and an apparent Km and Vmax for furfural
      of 1.5x10(-4)M and 28.5 micromol/min/mg of protein, respectively. It catalyzes
      the essentially irreversible reduction of furfural with NADPH, is specific for
      NADPH as cofactor, and is relatively specific for the reduction of furfural and
      benzaldehyde; 2-acetylfuran, xylose, and glucose were not reduced, while
      acetaldehyde was reduced at a rate 25-fold lower than furfural. This is the first
      description of a furfural reductase which, based upon size and substrate
      specificity, appears to represent a new type of alcohol-aldehyde oxido-reductase.
      The conversion of relatively toxic furfural to less toxic furfuryl alcohol
      suggests a beneficial role for this enzyme in mitigating furfural toxicity
      encountered during ethanol production from lignocellulosic biomass.

PMID- 16111780
TI  - Novel detection system for biomolecules using nano-sized bacterial magnetic
      particles and magnetic force microscopy.
AB  - A system for streptavidin detection using biotin conjugated to nano-sized
      bacterial magnetic particles (BMPs) has been developed. BMPs, isolated from
      magnetic bacteria, were used as magnetic markers for magnetic force microscopy
      (MFM) imaging. The magnetic signal was obtained from a single particle using MFM
      without application of an external magnetic field. The number of biotin
      conjugated BMPs (biotin-BMPs) bound to streptavidin immobilized on the glass
      slides increased with streptavidin concentrations up to 100 pg/ml. The minimum
      streptavidin detection limit using this technique is 1 pg/ml, which is 100 times
      more sensitive than a conventional fluorescent detection system. This is the
      first report using single domain nano-sized magnetic particles as magnetic
      markers for biosensing. This assay system can be used for immunoassay and DNA
      detection with high sensitivities.

PMID- 16111781
TI  - Modelling of translation of human protein disulfide isomerase in Escherichia coli
      A case study of gene optimisation.
AB  - Recombinant human protein disulfide isomerase (PDI) was expressed in vivo in
      Escherichia coli using a non-optimised gene sequence and an optimised sequence
      with four 5' codons substituted by synonymous codons that take less time to
      translate. The optimisation resulted in a 2-fold increase of total PDI
      concentration and by successive optimisation with expression at low temperature
      in a 10-fold increase of the amount of soluble PDI in comparison with the
      original wild-type construct. The improvement can be due to a faster clearing of
      the ribosome binding site on the mRNA, elevating the translation initiation rate
      and resulting in higher ribosome loading and better ribosome protection of the
      PDI mRNA against endonucleolytic cleavage by RNase. This hypothesis was supported
      by a novel computer simulation model of E. coli translational ribosome traffic
      based upon the stochastic Gillespie algorithm. The study indicates the
      applicability of such models in optimisation of recombinant protein sequences.

PMID- 16111782
TI  - Engineered proteins containing the cohesin and dockerin domains from Clostridium
      thermocellum provides a reversible, high affinity interaction for biotechnology
      applications.
AB  - The cohesin-dockerin interaction, which is responsible for the formation of the
      cellulosome complex of cellulolytic bacteria, is a calcium-dependent, high
      affinity interaction. In this study, the cohesin (Cip7) and dockerin (Doc)
      domains of Clostridium thermocellum were fused to the cellulose-binding domain
      (CBD) of C. cellulovorans and the antibody-binding domain, protein LG,
      respectively, to form CBD-Cip7 and LG-Doc. Immobilised CBD-Cip7 was able to bind
      LG-Doc and subsequently antibody as determined using surface plasmon resonance.
      Binding was reversed by the removal of Ca2+ with EDTA. The dockerin containing
      fusion protein was affinity purified using an immobilised cohesin domain. Elution
      of the LG-Doc from the cohesin column was with EDTA. This affinity chromatography
      was repeated using an LG-dockerin column for the purification of cohesin fusion
      protein. The fusion proteins created in this report have shown that the
      properties of the cohesin and dockerin domains can be transferred to other
      protein domains and that the interaction between the cohesin and dockerin is
      specific, Ca2+ -dependent and reversible. We have shown that the cohesin-dockerin
      interaction has several properties making it suitable for use in recombinant
      fusion protein production and purification.

PMID- 16111783
TI  - Controlled release of the herbicide simazine from computationally designed
      molecularly imprinted polymers.
AB  - The present study describes the development of materials suitable for
      environmental control of algae. Molecularly imprinted polymers (MIPs) were used
      as simazine carriers able to provide the controlled release of simazine into
      water. Three polymers were designed using computational modelling. The selection
      of methacrylic acid (MA) and hydroxyethyl methacrylate (HEM) as functional
      monomers was based on results obtained using the Leapfrog algorithm. A cross
      linked polymer made without functional monomers was also prepared and tested as a
      control. The release of simazine from all three polymers was studied. It was
      shown that the presence of functional monomers is important for polymer affinity
      and for controlled release of herbicide. The speed of release of herbicide
      correlated with the calculated binding characteristics. The high-affinity MA
      based polymer released approximately 2% and the low-affinity HEM-based polymer
      released approximately 27% of the template over 25 days. The kinetics of simazine
      release from HEM-based polymer show that total saturation of an aqueous
      environment could be achieved over a period of 3 weeks and this corresponds to
      the maximal simazine solubility in water. The possible use of these types of
      polymers in the field of controlled release is discussed.

PMID- 16111784
TI  - Radiation recall dermatitis with pemetrexed.
AB  - Pemetrexed has recently been approved for use in combination with cisplatin as
      first-line chemotherapy for malignant pleural mesothelioma (MPM). Radiation
      therapy is frequently administered to the thoracic orifices and no data are
      available about the interactions between radiotherapy and pemetrexed. We report
      the first case of radiation recall dermatitis occurring after pemetrexed
      chemotherapy in a patient with MPM previously treated with radiation therapy to
      the thoracoscopy and drainage orifices. The patient received chemotherapy with
      pemetrexed and cisplatin 19 days after completion of chest wall radiation therapy
      delivering 21 gray in 3 days. Conventional premedication by folic acid and
      intramuscular administration of Vitamin B12 and prednisolone was correctly
      performed. Twelve days later, confluent erythematous and pruritus rash of the
      irradiated skin was observed. The toxicity grade of this lesion was evaluated at
      2 according to the Acute Radiation Morbidity Scoring Criteria proposed by the
      Radiation Therapy Oncology Group. Pemetrexed challenge was performed without
      worsening of skin lesions. Three weeks later, skin cicatrisation was observed
      after a desquamative phase. Persistent hyperpigmentation was seen in the
      irradiated skin. Pemetrexed could also act as a radiosensitizing agent that
      should be used with care for several weeks after radiotherapy.

PMID- 16111785
TI  - Body dissatisfaction in females varies according to deprivation state and is
      modified by weight rather than restraint status.

PMID- 16111786
TI  - Altered gene expression and neuropathology in Alzheimer's disease.

PMID- 16111787
TI  - Live attenuated bluetongue vaccine viruses in Dorset Poll sheep, before and after
      passage in vector midges (Diptera: Ceratopogonidae).
AB  - The aim of this study was to address concerns associating with the use of BTV
      attenuated commercial vaccines in European sheep. These concerns include
      development of viraemia, possibility of transmission by vectors, reversion to
      virulence and re-assortment with wild-type viruses. The two vaccine viruses (BTV
      2 and 9) replicated in two species of Culicoides subsequent to oral infection
      reaching titres suggesting transmission would occur. Viraemia in Dorset Poll
      sheep inoculated with either vaccine or insect passaged vaccine viruses persisted
      for up to 17 days, recording titres that ranged from 2.5 to 6.25
      log(10)TCID(50)/ml, which is easily sufficient to infect vector Culicoides.
      Moderate to severe clinical signs of BT, albeit short lived, were observed in
      sheep following vaccination. However, to date there is no evidence of increasing
      virulence following two sequential passages through the vectors.

PMID- 16111788
TI  - Declining invasive pneumococcal disease in the U.S. elderly.
AB  - In 2000, pneumococcal conjugate vaccine (PCV7) was recommended for young
      children. By 2002-2003, 48.6% had been fully immunized. Using Medicare
      administrative, we found that the rates of invasive pneumococcal disease (IPD)
      hospitalizations in the elderly in the 2000-2001, 2001-2002 and 2002-2003, were
      22.6, 30.2, and 40.6% lower, respectively, than during the baseline period, 1996
      1997 through 1999-2000 (range 35.1/100,000 to 38.3/100,000). Pneumococcal
      polysaccharide vaccine (PPV23) has been recommended for the elderly, since 1989.
      PPV23 vaccination rates in the elderly increased by 25.2% during the baseline
      period but by <5% during the period PCV7 has been available. Thus, during the
      period that PCV7 vaccine has been used in children, rates of IPD in the elderly
      have declined appreciably more compared to the immediately prior period when
      PPV23 was the only vaccine available.

PMID- 16111789
TI  - High levels of serum antibodies to merozoite surface protein 2 of Plasmodium
      falciparum are associated with reduced risk of clinical malaria in coastal Kenya.
AB  - The merozoite surface protein (MSP) 2 is a vaccine candidate antigen of
      Plasmodium falciparum that is polymorphic in natural populations. In a
      prospective cohort study in two coastal populations of Kenya using recombinant
      proteins derived from the two major allelic types of MSP2, high serum levels of
      IgG to MSP2 were associated with protection from clinical malaria. This
      protection was independent of that associated with antibodies to another vaccine
      candidate antigen (AMA1) in these populations. However, low antibody levels to
      MSP2 appeared to be associated with increased susceptibility to malaria within
      people who were parasite negative at the time of serum collection. These data
      suggest that an MSP2 based vaccine should be designed to induce high level
      antibody responses against the different MSP2 types present globally in P.
      falciparum populations and that MSP2 could be combined with other P. falciparum
      antigens to form a multi-component malaria vaccine.

PMID- 16111790
TI  - A short report on the highlights of world-wide development of RIX4414: a North
      American experience comparative evaluation of safety and immunogenicity of two
      dosages of an oral live attenuated human rotavirus vaccine (RIX4414) in infants
      in the United States and Canada.
AB  - This randomized, double-blind trial conducted in the US and Canada was conducted
      to compare the safety and immunogenicity of two dosages of live attenuated oral
      monovalent G1 human rotavirus (HRV) vaccine administered orally at a 2-month
      interval concomitantly with routine childhood vaccines to healthy infants 5-15
      weeks of age. No SAEs considered related to vaccine were reported. The incidence
      of solicited symptoms was similar among treatment groups during the 15-day post
      vaccination surveillance periods. No significant difference in vaccine take after
      2 doses (88.0% in high dose group and 81.5% in low dose group) was seen between
      vaccine groups. Two doses of either dosage level of HRV vaccine administered
      concurrently with routine childhood vaccines to healthy infants were well
      tolerated and elicited excellent vaccine takes.

PMID- 16111791
TI  - Radiological dispersion devices: are we prepared?
AB  - Already before the events of September 11th 2001 concern was raised about the
      spread of orphan sources and their potential use in Radiological Dispersion
      Devices by terrorist groups. Although most of the simulated scenarios foresee a
      rather limited direct health impact on the population, the affected region would
      suffer from the indirect consequences such as social disruption, cleanup
      requirements and economic costs. The nature of such a radiological attack would
      anyway be different compared to conventional radiological accidents, basically
      because it can happen anywhere at any time. Part of the response resides in a
      general preparedness scheme incorporating attacks with Radiological Dispersion
      Devices. Training of different potential intervention teams is essential. The
      response would consist of a prioritised list of actions adapted to the
      circumstances. As the psychosocial dimension of the crisis could be worse than
      the purely radiological one, an adapted communication strategy with the public
      aspect would be a key issue.

PMID- 16111792
TI  - Arthroscopic triangular fibrocartilage complex debridement using radiofrequency
      probes.
AB  - The initial results of using radiofrequency probes for debridement of a torn
      triangular fibrocartilage complex were studied in 20 patients with a mean age of
      44 (range 27-56) years presenting with ulnar-sided wrist pain. On arthroscopic
      examination, 18 central and two radial triangular fibrocartilage complex tears
      were identified and debrided to a stable rim using radiofrequency probes. The
      mean follow-up was 22 (range 9-35) months. Seventeen patients experienced
      substantial pain relief. In three, the pain was unchanged. The mean flexion
      extension arc was 132 degrees , pronosupination arc 155 degrees and mean grip
      strength was 83% of that of the unaffected side. Using the modified Mayo wrist
      score, there were ten excellent, seven good and three fair results. No
      perioperative complications occurred. Radiofrequency probes were found to be safe
      and effective for use in triangular fibrocartilage complex debridement. These
      results compare favourably with other standard methods of treatment of this
      problem.

PMID- 16111793
TI  - Comparative acute toxicity of organic pollutants and reference values for
      crustaceans. I. Branchiopoda, Copepoda and Ostracoda.
AB  - The acute toxicity of 468 organic pollutants to planktonic crustaceans
      (Branchiopoda, Copepoda and Ostracoda) from pre-existing data was compared by
      means of statistical analysis and relative tolerance indices (Trel). A surrogate
      species commonly used in toxicity bioassays (Daphnia magna) showed toxicity
      levels--within one order of magnitude--similar to all other Cladocera species, at
      least for 82% of the chemicals studied. All neurotoxic insecticides except
      neonicotinoids, PCBs, organometallic compounds and PAHs are the most toxic
      substances to these organisms. Sensitivity levels among taxa were compared for
      individual chemicals as well as groups of chemicals with similar characteristics.
      Whilst there are marked differences in sensitivity among taxa and particular
      groups of chemicals, no consistent trends were found for freshwater and saltwater
      species in relation to the latter groups. No correlation between LC50 and size of
      these organisms was found other than by chance, making extrapolations based on
      allometric equations impossible.

PMID- 16111794
TI  - Depression, implicit memory, and self: a revised memory model of emotion.
AB  - Cognitive constructs are explored for clinical psychologists interested in
      cognitive phenomena in depression. Both traditional and modern memory constructs
      are outlined and described with attention to their contribution to understanding
      depression. In particular, the notions of memory construction, self-schemas, and
      autobiographical memory (per [Conway, M.A. (2001). Sensory-perceptual episodic
      memory and its context: Autobiographical memory. Philosophical Transactions of
      the Royal Society of London: Biological Sciences, 356, 1375-1384.]) are
      discussed. Then, the phenomenon of implicit memory is described as a way to bring
      these constructs together to understand depression. The Rehm and Naus (1990)
      [Rehm, L.P., and Naus, M.J. (1990). A memory model of emotion. In Ingram, R.E.
      (Ed.), Contemporary Psychological Approaches to Depression (pp. 23-35). New York:
      Plenum Press.] memory model of emotion is updated and expanded to include these
      cognitive constructs, and depression is viewed from the perspective of
      understanding interactions between explicit and implicit memory processes.

PMID- 16111795
TI  - Concentration-time-response modeling for acute and short-term exposures.
AB  - Risk of health effects from acute and short-term exposure depends on exposure
      time as well as exposure concentration. A general approach to extending a
      concentration-response model to include time as a variable is described using
      mortality of rats exposed to hydrogen sulfide (H(2)S) as an example. This
      particular example resulted in a logit model with concentration-time (c-t)
      relationship linear in time and log-concentration. It provided an improved
      statistical fit, based on the Akaike information criterion in the observed time
      range, 30 m-360 m, over implementing the c-t relationship of [ten Berge, W.F.,
      Zwart, A., Appelman, L.M., 1986. Concentration-time mortality response
      relationship of irritant and systemically acting vapours and gases. J. Hazard.
      Mater. 13, 301--309] as a default in the logit model. This approach also
      indicated that there might be a fundamental difference in the relationship
      between concentration, time, and response at short exposure times, somewhere less
      than 30 m, a hypothesis for further consideration from a biological perspective.
      In general, the proposed approach provides flexibility to develop a concentration
      time-response model, and the associated concentration-time relationship, from the
      data. Interpretation and potential implications, however, need to be considered
      within the context of biological plausibility as well. Implementation of the
      proposed approach requires adequate data for separate concentration-response
      modeling at each of several exposure durations.

PMID- 16111796
TI  - Aberrant folate status in schizophrenic patients: what is the evidence?
AB  - A vast amount of case reports, open studies and, to a lesser extent, case-control
      studies have been published on the topic of psychopathology and folate
      deficiency. These studies reported a high incidence of serum folate deficiency in
      patients with various psychiatric disorders. Folate deficiency seems to be a
      particular consistent finding in depressive patients. The evidence for an
      association between aberrant folate status and schizophrenia seems less
      convincing. The lack of stringent methodology such as inclusion of age- and sex
      matched controls was thought to be the main reason for the inconclusive results.
      The purpose of this article is to review the published case-control studies that
      provide data on folate levels in the population of patients with schizophrenia.
      Data extracted from these studies comprised methodological design, clinical
      characteristics and folate measurements. We found that none of the 7 case-control
      studies included in this review (in total 325 cases and 560 control subjects)
      explicitly reported on all critical factors in the assessment of folate. In
      addition, only three studies found lower plasma folate levels more frequently in
      patients with schizophrenia compared to controls. Further research on this topic
      is required to clarify the relationship between folate status and schizophrenia
      and should avoid the methodological pitfalls mentioned in this review. In
      addition, research should also focus on polymorphisms of genes related to folate
      metabolism.

PMID- 16111797
TI  - The central nervous system in animal models of hyperhomocysteinemia.
AB  - Growing epidemiological evidence of associations between mildly elevated plasma
      homocysteine with age-related cognitive impairment, neurodegenerative and
      cerebrovascular disease has stimulated interest in the role of homocysteine in
      neurological and neuropsychiatric disorders. Homocysteine is an intermediate in
      the folate, vitamin B12 and B6 dependent pathways of one-carbon and sulfur amino
      acid metabolism. Impairments of these pathways may cause CNS dysfunction by
      promoting the intracellular generation of homocysteine, which is postulated to
      have vasotoxic and neurotoxic properties. It might also inhibit the methylation
      of myelin basic protein and membrane phospholipids, or disrupt biogenic amine
      metabolism and many other vital CNS reactions. However, it is unclear which, if
      any, of these putative mechanisms underlies the epidemiological associations.
      Genetic mouse models of hyperhomocysteinemia suggest that the primary metabolic
      disturbances rather than homocysteine per se may be important in determining
      neurological outcomes. However, severe and early developmental abnormalities in
      these mice limit their usefulness for understanding the relation of
      hyperhomocysteinemia to adult CNS disorders. Pharmacologic and dietary studies on
      homocysteine in rodents have reported heightened neuronal sensitivity to
      neurotoxic insults, neurochemical abnormalities and cerebrovascular dysfunction.
      Such studies are consistent with a causal relationship, but they fail to
      distinguish between effects that might result from a dietary imbalance and those
      that might be caused by homocysteine per se. Future work should be directed
      towards refining these models in order to distinguish between the effects of
      homocysteine and its determinants on neurological and behavioral outcomes that
      represent different CNS disorders.

PMID- 16111798
TI  - History of chemical and biological warfare agents.
AB  - Chemical and biological warfare agents constitute a low-probability, but high
      impact risk both to the military and to the civilian population. The use of
      hazardous materials of chemical or biological origin as weapons and for homicide
      has been documented since ancient times. The first use of chemicals in terms of
      weapons of mass destruction goes back to World War I, when on April 22, 1915
      large amounts of chlorine were released by German military forces at Ypres,
      Belgium. Until around the 1970s of the 20th century, the awareness of the threat
      by chemical and biological agents had been mainly confined to the military
      sector. In the following time, the development of increasing range delivery
      systems by chemical and biological agents possessors sensitised public attention
      to the threat emanating from these agents. Their proliferation to the terrorists
      field during the 1990s with the expanding scale and globalisation of terrorist
      attacks suggested that these agents are becoming an increasing threat to the
      whole world community. The following article gives a condensed overview on the
      history of use and development of the more prominent chemical and biological
      warfare agents.

PMID- 16111799
TI  - Survival of resin-bonded porcelain veneer crowns placed with and without metal
      reinforcement.
AB  - OBJECTIVES: The purpose of this retrospective case study of dental records was to
      compare the long-term failure rates and modes for resin-bonded sintered
      feldspathic porcelain veneer crowns (RBPVCs) either containing or without metal
      substructure reinforcement. METHODS: Two prosthodontists placed 62 RBPVCs
      fabricated with, and 167 without, metal reinforcement in 143 older adolescent and
      adult patients treated in a private practice. Clinical judgement determined the
      type of crown design placed. Preparation margins were generally finished on
      enamel, and all crowns occluded with opposing teeth. Observations included the
      patients, operators, crown designs and failure modes. Chi-square or Fisher's
      exact tests and life table survival statistics were used to evaluate the findings
      (alpha = 0.05). RESULTS: Over five years, failures occurred in 14.5% of RBPVCs
      fabricated with, and in 18.6% without, metal reinforcement. Cumulative survival
      estimates were 74.3 +/- 8.5(Standard Error)% and 72.9 +/- 4.8(SE)%, respectively
      (P = 0.96). Mandibular posterior crowns comprised 27.1% of the placements, but
      47.5% of the failures. Bulk fracture of porcelain occurred in 7.0% of the crowns,
      all without metal reinforcement. Minor porcelain fractures and debonding were
      less frequent in both types of crowns. Persistent pulpitis occurred in 3.5% of
      all teeth. CONCLUSIONS: There was a significant risk of failure for sintered
      porcelain RBPVCs placed as posterior restorations. Although metal reinforcement
      was able to reduce the risk of bulk fracture of porcelain, other causes of
      failure were less affected.

PMID- 16111800
TI  - Effects of cattle manure on erosion rates and runoff water pollution by faecal
      coliforms.
AB  - The large quantities of slurry and manure that are produced annually in many
      areas in which cattle are raised could be an important source of organic matter
      and nutrients for agriculture. However, the benefits of waste recycling may be
      partially offset by the risk of water pollution associated with runoff from the
      fields to which slurry or manure has been applied. In this paper, the effects of
      cattle manure application on soil erosion rates and runoff and on surface water
      pollution by faecal coliforms are analysed. Rainfall simulations at a rate of 70
      mm h(-1) were conducted in a sandy loam soil packed into soil flumes (2.5m long x
      1m wide) at a bulk density of 1400 kg m(-3), with and without cattle slurry
      manure applied on the surface. For each simulation, sediment and runoff rates
      were analysed and in those simulations with applied slurry, presumptive faecal
      coliform (PFC) concentrations in the runoff were evaluated. The application of
      slurry on the soil surface appeared to have a protective effect on the soils,
      reducing soil detachment by up to 70% but increasing runoff volume by up to 30%.
      This practice implies an important source of pollution for surface waters
      especially if rainfall takes place within a short period after application. The
      concentrations of micro-organisms (presumptive faecal coliforms (PFCs)) found in
      water runoff ranged from 1.9 x 10(4) to 1.1 x 10(6) PFC 100mL(-1), depending on
      the initial concentration in the slurry, and they were particularly high during
      the first phases of the rainfall event. The result indicates a strong
      relationship between the faecal coliforms transported by runoff and the organic
      matter in the sediment.

PMID- 16111801
TI  - The monoculture vs. rotation strategies in forestry: formalization and prediction
      by means of Markov-chain modelling.
AB  - The monoculture strategy of forest management, where the same tree species (e.g.,
      Picea abies) is cultivated in a number of successive planting-growing-felling
      cycles, is generally considered to be economically efficient, yet not sustainable
      as it reduces biodiversity in the forest. The sound alternative suggests a long
      term strategy of forest management in which different forest types rotate either
      with planting after clear cutting, or by natural forest succession, yet the
      commercial output remains dubious. We suggest an approach to formalization and
      modelling forest dynamics in the long-term by means of Markov chains, the
      monoculture strategy resulting in an absorbing chain and the rotation one in a
      regular chain. The approach is illustrated with a case study of Russkii Les, a
      managed forest located in the Moscow Region, Russia, and the nearby forest
      reserve having been used as a data source for undisturbed forest dynamics.
      Starting with conceptual schemes of transitions among certain forest types
      (states of the chain) in the monoculture and rotation cases, we estimated the
      transition probabilities by an original method based on average duration of the
      corresponding states and on the likelihood of alternative transitions from a
      state into the next one. Formal analysis of the regular chain reveals an
      opportunity to achieve particular management objectives within the rotation
      strategy, in particular, to get the distribution of forest types in accordance
      with an adopted hierarchy of their commercial values, i.e. more valuable types
      have greater shares.

PMID- 16111802
TI  - Combination of thiol antioxidant Silibinin with Brostallicin is associated with
      increase in the anti-apoptotic protein Bcl-2 and decrease in caspase 3 activity.
AB  - The cytotoxic activity of Brostallicin was previously shown to be enhanced in the
      presence of high glutathione and glutathione transferase levels. We hypothesized
      that thiol antioxidants, N-acetylcysteine and Silibinin, could potentiate
      Brostallicin's cytotoxicity in a similar way. HepG2 and CNE-2 cells were treated
      with N-acetylcysteine, Silibinin and Brostallicin, either alone or in
      combination. Surprisingly, we found that NAC and Silibinin had adverse effects on
      Brostallicin's cytotoxicity. The mechanism underlying the interaction involved
      the apoptotic pathway as we demonstrated an increase in Bcl-2 protein levels and
      decrease in caspase 3 activity with the Silibinin-Brostallicin combination.

PMID- 16111803
TI  - P53 Codon 72 polymorphisms: a case-control study of gastric cancer and potential
      interactions.
AB  - P53 codon 72 polymorphisms have been reported to be associated with cancers of
      the lung, esophagus and cervix. However, there have been no reports on the
      interaction of select risk factors and p53 codon 72 polymorphisms in gastric
      cancer susceptibility. 155 gastric cancer cases and 134 cancer-free controls were
      enrolled at the Memorial Sloan Kettering Cancer Center (MSKCC) from November 1992
      to November 1994. The crude odds ratio (OR1) associated with the (Pro/Pro)
      polymorphism and the risk of gastric cancer was 1.27 (0.70-2.33). Adjusting for
      age, sex, race and education (OR2) and further adjusting for BMI, calories,
      sodium, smoking, vitamin C, fiber, alcohol, fat, and H. pylori status (OR3) did
      not yield significant results. Significant joint effects were associated with
      high fat consumption (OR1=2.61 (95% CI:1.13-6.06); OR2=2.85 (95% CI:1.14-7.15)
      for total cancers and for proximal tumors (OR1=2.56 (95%CI:1.00-6.54)). The low
      vitamin C intake/high-risk polymorphism group (Pro/Pro) had an OR1 of 4.82 (95%
      CI: 1.72-13.45) and the OR2 was 6.19 (95% CI: 2.08-18.40) for distal tumors. The
      point estimates were increased for interaction odds ratios but not statistically
      significant (OR1=4.25 (95% CI: 0.66-27.50); OR2=4.73 (95% CI: 0.67-33.43);
      OR3=5.55 (95% CI: 0.66-46.47)). Further studies specifically looking at proximal
      and distal tumors are required to confirm any potential interaction between the
      p53 codon 72 polymorphisms and environmental risk, in particular low dietary
      vitamin C and high fat consumption.

PMID- 16111804
TI  - Loss of imprinting and promoter usage of the IGF2 in laryngeal squamous cell
      carcinoma.
AB  - The gene for insulin-like growth factor two, IGF2 is maternally imprinted.
      Fifteen heterozygous samples were analyzed for the IGF2 imprinting status and
      promoter usage. IGF2 LOI was detected in four non-tumorous tissues and in six
      laryngeal squamous cell carcinoma (LSCC) tumors. There was no clear pattern of
      specific promoter activity in LSCC tumors and the adjacent normal tissues. P1
      promoter usage was active in eight LSCCs, among them four with LOI. As it was
      activated in four tumors with maintenance of imprinting (MOI) and four non
      tumors, we concluded that P1 promoter is not exclusively connected with IGF2 LOI
      in LSCC.

PMID- 16111805
TI  - Spontaneous photon emission and delayed luminescence of two types of human lung
      cancer tissues: adenocarcinoma and squamous cell carcinoma.
AB  - We measured spontaneous photon emission and delayed luminescence from human
      cancerous lung tissue and compared with those from adjacent normal lung tissue.
      For the detection of extremely weak photon emission from tissue we used a
      sensitive photomultiplier tube attached to a dark chamber. The samples were
      illuminated with a metal halide lamp for measurement of delayed luminescence.
      Extracted samples from surgery were measured within an hour. We found that the
      delayed luminescence showed salient aspects in making discrimination between
      tumor and adjacent normal tissue. Squamous cell carcinoma had more prominent
      character in delayed luminescence than adenocarcinoma.

PMID- 16111806
TI  - Altered iron metabolism, transferrin receptor 1 and ferritin in patients with
      colon cancer.
AB  - In this study, the level and distribution of transferrin receptor 1 (TfR1) and
      ferritin in colorectal carcinoma and in normal colon epithelium has been
      determined relative to the tumor stage and iron status of patients using
      immunohistochemical staining methods. While the majority of carcinoma patients
      were anemic, no relationship between the level of colon tissue ferritin and TfR1
      and the systemic parameters of iron metabolism was evident. Furthermore, no
      association between ferritin content and the grade of colorectal carcinoma was
      observed. However, a relationship between the expression of TfR1 and the grade of
      colorectal carcinoma was observed. In this case high expression of TfR1 was found
      in colorectal carcinoma samples of Dukes A or B grade, and well differentiated
      colorectal carcinoma cells. In comparison, weak or no expression of TfR1 was
      observed in carcinoma samples of Dukes C or D grade with poorly differentiated
      cells and in carcinoma samples that had lymph node infiltration and distant
      metastasis.

PMID- 16111807
TI  - Elevation of cyclooxygenase-2 is related to lymph node metastasis in
      adenocarcinoma of uterine cervix.
AB  - In a previous study, we demonstrated that elevation of COX-2 is significantly
      associated with lymph node metastasis in squamous cell carcinoma (SCC) of cervix.
      The main objective of this study is to characterize the relationship between
      elevation of COX-2 and its possible clinical role in adenocarcinoma (AC) of
      cervix. Using immunohistochemistry, we examined COX-2 expression levels in 84
      patients with AC of uterine cervix [71 ACs, 13 adenosquamous carcinomas (ASCs)].
      Elevation of COX-2 was correlated with clinicopathological variables and p53
      expression, as detected by immunohistochemistry. Elevation of COX-2 was detected
      in 13.0% (11 of 84) of the tumors. Elevation of COX-2 was significantly
      correlated with histologic type (AC 8.5% vs. ASC 38.5%, P=0.011). Both tumor
      stage and lymph node metastasis were correlated with elevation of COX-2 with a
      borderline significance (P=0.062 and 0.068, respectively). Elevation of p53 was
      not associated with elevation of COX-2. The association between lymph node
      metastasis and elevation of COX-2 was stronger in cases of AC than in cases of
      ASC (28.4 vs. 4.3%, P=0.023). According to the results of univariate analysis,
      elevation of COX-2 was significantly associated with decreased overall survival
      (P=0.003, log-rank test). However, multivariate analyses revealed that only tumor
      stage was independently associated with overall survival, suggesting that
      elevation of COX-2 itself may not be an independent prognostic factor. The
      present study shows that elevation of COX-2 may contribute to lymph node
      metastasis in AC of uterine cervix. This suggests that the potential therapeutic
      role of COX-2 inhibitors should be validated, not only in SCC, but also in AC of
      uterine cervix.

PMID- 16111808
TI  - Reduction of organic matter and trihalomethane formation potential in reclaimed
      water from treated industrial estate wastewater by coagulation.
AB  - Raw water from treated industrial estate wastewater in northern Thailand was used
      in jar-test coagulation experiments with variations of separate alum and ferric
      chloride dosages from 10 to 80 mg/L at pH conditions ranging from 5 to 6.5.
      Natural organic matter (NOM) surrogates and trihalomethane formation potential
      (THMFP) were determined to study their reduction. The obtained results showed
      that total organic carbon (TOC) were gradually reduced from the average value of
      about 6.1 mg/L to a level of about 4.0 mg/L by alum and ferric chloride dosages
      of approximately 40 mg/L. Moreover, dissolved organic carbon (DOC) were reduced
      from an average value of 5.1 mg/L to a level of about 4.0 mg/L by alum and ferric
      chloride dosages of approximately 40 mg/L. Specific ultraviolet absorption (SUVA)
      were decreased from an average value of approximately 4.7 L/mgm to a level of
      about 2 L/mgm by alum and ferric chloride dosages of approximately 20 mg/L. In
      addition, chlorine demands at 1 day reaction were the same as those of 7-day
      demands with a correlation coefficient of 0.98 (n = 10, correlation significant
      at the 0.01 level). Interestingly, chloroform of approximately 65 and 60% of
      total THMFP was found as the predominant THMFP species in treated industrial
      estate wastewater and reclaimed water, respectively, in comparison with other THM
      species. Maximum THMFP percentage removal of 25 and 28 by using alum and ferric
      chloride dosages of about 80 mg/L at pH 5.5 and 5 were obtained, respectively, at
      the examined conditions.

PMID- 16111809
TI  - The use of generic failure frequencies in QRA: the quality and use of failure
      frequencies and how to bring them up-to-date.
AB  - Quantitative Risk Assessment (QRA) is a method which is often used in the
      chemical industry and, in some countries, also in land-use planning. In QRA
      calculations the frequency of an accident scenario is most often assessed by a
      generic failure frequency approach. The credibility and validity of the failure
      frequencies used in the Netherlands for land-use planning is evaluated by means
      of an historical review. Furthermore, the possibility is presented how these
      generic data can be revised and updated.

PMID- 16111810
TI  - Pre-treatment processes of Azolla filiculoides to remove Pb(II), Cd(II), Ni(II)
      and Zn(II) from aqueous solution in the batch and fixed-bed reactors.
AB  - Intact and treated biomass can remove heavy metals from water and wastewater.
      This study examined the ability of the activated, semi-intact and inactivated
      Azolla filiculoides (a small water fern) to remove Pb(2+), Cd(2+), Ni(2+) and
      Zn(2+) from the aqueous solution. The maximum uptake capacities of these metal
      ions using the activated Azolla filiculoides by NaOH at pH 10.5 +/- 0.2 and then
      CaCl(2)/MgCl(2)/NaCl with total concentration of 2 M (2:1:1 mole ratio) in the
      separate batch reactors were obtained about 271, 111, 71 and 60 mg/g (dry
      Azolla), respectively. The obtained capacities of maximum adsorption for these
      kinds of the pre-treated Azolla in the fixed-bed reactors (N(o)) were also very
      close to the values obtained for the batch reactors (Q(max)). On the other hand,
      it was shown that HCl, CH(3)OH, C(2)H(5)OH, FeCl(2), SrCl(2), BaCl(2) and AlCl(3)
      in the pre-treatment processes decreased the ability of Azolla to remove the
      heavy metals in comparison to the semi-intact Azolla, considerably. The kinetic
      studies showed that the heavy metals uptake by the activated Azolla was done more
      rapid than those for the semi-intact Azolla.

PMID- 16111811
TI  - Land use planning in India.
AB  - India was the first country to provide for the protection and improvement of
      environment in its constitution. Land use planning (LUP) or siting of industries
      has been taken up at the State and Central (Federal) levels over the last few
      decades. LUP is critical for all types of industries and new residential
      colonies, but is especially so for the chemical industries. With the experience
      gained, more coherence in LUP policies is emerging. A few prominent cases of
      siting of industry, some mixed with public outcry, that have affected the
      policies are noted in the text. Various factors which affect LUP in India are:
      population density, infrastructure (roads, power, communication, etc.), level of
      industrialization in different parts, need for creation of jobs, eco-sensitive
      regions, tribal regions, historical monuments, etc. This paper discusses the
      current scene in India and the near future aspects.

PMID- 16111812
TI  - Photodegradation of 17beta-estradiol in water by UV-vis/Fe(III)/H2O2 system.
AB  - Photodegradation of 17beta-estradiol (E2) in aqueous solutions by UV
      vis/Fe(III)/H(2)O(2) system, namely Photo-Fenton system, was preliminarily
      investigated under a 250 W metal halide lamp (lambda > or = 313 nm). The
      influences of initial pH value, initial concentration of H(2)O(2) and E2 on
      photodegradation efficiency of E2 were discussed and the amount of CO(2) produced
      by the photodegradation reaction was measured. The results indicates that E2
      could be decomposed efficiently in UV-vis/Fe(III)/H(2)O(2) system. Under the
      condition of 10.0 micromol L(-1) Fe(III), 1000 micromol L(-1) H(2)O(2) and pH
      3.0, the degradation efficiency of 18.4 micromol L(-1) E2 reach 75.2% after the
      irradiation of 160 min. Over the range of pH 3.0-6.0, the higher acidity, the
      higher the degradation efficiency of E2 and initial reaction rate are. The
      degradation efficiency of E2 increases with increasing of initial concentration
      of H(2)O(2) and with decreasing of initial concentration of E2. The E2
      mineralization efficiency increases with reaction time but the mineralization
      efficiency was lower. When the initial concentration of Fe(III) and H(2)O(2) were
      10.0 and 1000 micromol L(-1), respectively, the mineralization efficiency of 18.4
      micromol L(-1) E2 solution with pH 3.0 was only 21.6% after 160 min irradiation.
      It is suggested that the mineralization occurred probably only at aromatic ring.

PMID- 16111813
TI  - The development of an audit technique to assess the quality of safety barrier
      management.
AB  - This paper describes the development of a management model to control barriers
      devised to prevent major hazard scenarios. Additionally, an audit technique is
      explained that assesses the quality of such a management system. The final
      purpose of the audit technique is to quantify those aspects of the management
      system that have a direct impact on the reliability and effectiveness of the
      barriers and, hence, the probability of the scenarios involved. First, an outline
      of the management model is given and its elements are explained. Then, the
      development of the audit technique is described. Because the audit technique uses
      actual major hazard scenarios and barriers within these as its focus, the
      technique achieves a concreteness and clarity that many other techniques often
      lack. However, this strength is also its limitation, since the full safety
      management system is not covered with the technique. Finally, some preliminary
      experiences obtained from several test sites are compiled and discussed.

PMID- 16111814
TI  - Nanomechanical characterization of human hair using nanoindentation and SEM.
AB  - Human hair is a nanocomposite biological fiber with well-characterized
      microstructures. Nanomechanical characterization of human hair can help to
      evaluate the effect of cosmetic products on hair surface, can provide a better
      understanding of the physicochemical properties of a wide variety of composite
      biological systems, and can provide the dermatologists with some useful markers
      for the diagnosis of hair disorders. The paper presents systematic studies of
      nanomechanical properties of human hair including hardness, elastic modulus and
      creep, using the nanoindentation technique. The samples include Caucasian, Asian
      and African hair at virgin, chemo-mechanically damaged and treated conditions.
      Hair morphology was studied using scanning electron microscopy (SEM). Indentation
      experiments were performed on both the surface and cross-section of the hair, and
      the indents were studied using SEM. The nanomechanical properties of hair as a
      function of hair composition, microstructure, ethnicity, damage and treatment are
      discussed.

PMID- 16111815
TI  - Comparing different formulae to test for gastrointestinal nematode resistance to
      benzimidazoles in smallholder goat farms in Mexico.
AB  - The objective was to examine the coincidence in the prevalence of benzimidazole
      (Bz) resistance in smallholder goat herds, as determined by three average-based
      and two individually-based faecal egg count reduction (FECR) tests. Nineteen
      smallholder goat herds with more than 30 animals were selected from 84 herds in
      Yucatan. Animals shedding 150 eggs/g of faeces (EPG) on day zero were randomly
      divided into two groups. The control group did not receive treatment and the
      treated group received fenbendazole (10mg/kg body weight per os). Feed was
      withdrawn for 16 h before treatment. Ten days after treatment, both groups were
      sampled to determine their FEC. Faecal cultures and identification of infective
      larvae were performed for estimating the proportions of genera of
      gastrointestinal nematodes (GIN) present. Presence of resistant GIN was
      determined with three different average-based FECR (FECR(1), FECR(2) and FECR(3))
      and two individually-based FECR (iFECR(1) and iFECR(2)). The prevalence of herds
      with Bz resistant nematodes (and 95% confidence interval (95% CI)) was calculated
      using each formula. Coincidence among formulae was estimated with Kappa values.
      The prevalence (+/- 95% CI) of Bz resistance calculated with FECR(1) (57.89 +/-
      22.20) had a high coincidence with iFECR(1) and iFECR(2) (Kappa values of 0.86
      and 0.79, respectively). The prevalence with FECR(2) (31.58 +/- 20.90) and
      FECR(3) (21.05 +/- 18.33) had a low coincidence with FECR(1) (Kappa < 0.50).
      Trichostrongylids found on Bz resistant farms were mainly Haemonchus spp.,
      however, some Trichostrongylus spp. and Oesophagostomum spp. were found too. The
      high coincidence between the standard average-based FECR(1) and the individually
      based formulae is encouraging and may suggest that either formula could be
      applied to smallholder farmers. Further laboratory studies are needed to confirm
      the resistance status in the herds.

PMID- 16111816
TI  - Monosynaptic circuitry of trigeminal proprioceptive afferents coordinating jaw
      movement with visceral and laryngeal activities in rats.
AB  - Jaw movement is intimately related to various oromotor and visceral functions
      such as feeding, swallowing, vocalization, respiration and cardiac function.
      Neuronal circuitry that links jaw movement and these visceral and oromotor
      functions is largely unknown. The purpose of this study is to determine whether
      the trigeminal proprioceptive and jaw-muscle spindle afferents send axons to and
      synapse with the motoneurons innervating visceral organs and laryngeal muscles
      utilizing multiple double-labeling and physiological approaches. Double labeling
      of anterograde tracing combined to retrograde transport was performed by
      injection of biotinylated dextran amine into the mesencephalic trigeminal nucleus
      and cholera toxin B subunit or horseradish peroxidase into the vagus nerve and
      the recurrent laryngeal nerve. Mesencephalic trigeminal nucleus neuronal
      terminals contacted with visceral and laryngeal muscle motoneurons in the
      ambiguus nucleus and the nearby intermediate reticular zone. By electron
      microscopic observation, we confirmed that mesencephalic trigeminal nucleus
      terminals made asymmetric axodendritic synapses with these motoneurons. Double
      labeling of physiologically characterized jaw muscle spindle afferent neurons
      combined with anti-choline acetyltransferase immunohistochemistry showed that jaw
      muscle spindle afferent boutons closely contacted choline acetyltransferase
      immunoreactive motoneurons in the ambiguus nucleus and intermediate reticular
      zone. This report is the first to demonstrate that the trigeminal proprioceptive
      afferents synapsed upon visceral and laryngeal muscle motoneurons and provide
      neuronal networks for the jaw-visceral and jaw-laryngeal coordination.

PMID- 16111817
TI  - Excitotoxic brain damage involves early peroxynitrite formation in a model of
      Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20
      tetrakis (4-sulfonatophenyl)porphyrinate iron (III).
AB  - Oxidative/nitrosative stress is involved in NMDA receptor-mediated excitotoxic
      brain damage produced by the glutamate analog quinolinic acid. The purpose of
      this work was to study a possible role of peroxynitrite, a reactive
      oxygen/nitrogen species, in the course of excitotoxic events evoked by quinolinic
      acid in the brain. The effects of Fe(TPPS) (5,10,15,20-tetrakis (4
      sulfonatophenyl)porphyrinate iron (III)), an iron porphyrinate and putative
      peroxynitrite decomposition catalyst, were tested on lipid peroxidation and
      mitochondrial function in brain synaptic vesicles exposed to quinolinic acid, as
      well as on peroxynitrite formation, nitric oxide synthase and superoxide
      dismutase activities, lipid peroxidation, caspase-3-like activation, DNA
      fragmentation, and GABA levels in striatal tissue from rats lesioned by
      quinolinic acid. Circling behavior was also evaluated. Increasing concentrations
      of Fe(TPPS) reduced lipid peroxidation and mitochondrial dysfunction induced by
      quinolinic acid (100 microM) in synaptic vesicles in a concentration-dependent
      manner (10-800 microM). In addition, Fe(TPPS) (10 mg/kg, i.p.) administered 2 h
      before the striatal lesions, prevented the formation of peroxynitrite, the
      increased nitric oxide synthase activity, the decreased superoxide dismutase
      activity and the increased lipid peroxidation induced by quinolinic acid (240
      nmol/microl) 120 min after the toxin infusion. Enhanced caspase-3-like activity
      and DNA fragmentation were also reduced by the porphyrinate 24 h after the
      injection of the excitotoxin. Circling behavior from quinolinic acid-treated rats
      was abolished by Fe(TPPS) six days after quinolinic acid injection, while the
      striatal levels of GABA, measured one day later, were partially recovered. The
      protective effects that Fe(TPPS) exerted on quinolinic acid-induced lipid
      peroxidation and mitochondrial dysfunction in synaptic vesicles suggest a primary
      action of the porphyrinate as an antioxidant molecule. In vivo findings suggest
      that the early production of peroxynitrite, altogether with the enhanced risk of
      superoxide anion (O2*-) and nitric oxide formation (its precursors) induced by
      quinolinic acid in the striatum, are attenuated by Fe(TPPS) through a recovery in
      the basal activities of nitric oxide synthase and superoxide dismutase. The
      porphyrinate-mediated reduction in DNA fragmentation simultaneous to the decrease
      in caspase-3-like activation from quinolinic acid-lesioned rats suggests a
      prevention in the risk of peroxynitrite-mediated apoptotic events during the
      course of excitotoxic damage in the striatum. In summary, the protective effects
      that Fe(TPPS) exhibited both under in vitro and in vivo conditions support an
      active role of peroxynitrite and its precursors in the pattern of brain damage
      elicited by excitotoxic events in the experimental model of Huntington's disease.
      The neuroprotective mechanisms of Fe(TPPS) are discussed.

PMID- 16111818
TI  - Instrumental learning, but not performance, requires dopamine D1-receptor
      activation in the amygdala.
AB  - Substantial experimental evidence exists suggesting a critical role for dopamine
      in reinforcer-related processes, such as learning and drug addiction. Dopamine
      receptors, and in particular D1 receptors, are widely considered as modulators of
      synaptic plasticity. The amygdala contains both dopamine terminals and dopamine
      D1 receptors and is intimately involved in motivation and learning. However,
      little is known about the involvement of D1 receptor activation in two subnuclei
      of the mammalian amygdala, the central nucleus and basolateral complex in
      instrumental learning. Following recovery from surgery and preliminary training,
      rats with bilateral indwelling cannulae aimed at the central nucleus or
      basolateral complex were trained to lever-press for sucrose pellets over 12
      sessions. Infusion of the selective D1 antagonist R(+)-7-chloro-8-hydroxy-3
      methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (0.3 nmol and
      3.0 nmol) prior to the first five training sessions dose-dependently impaired
      instrumental learning when compared with vehicle-infused controls. All rats were
      then exposed to five sessions drug-free; lever-pressing quickly reached equal
      levels across groups. A drug infusion prior to an 11th session revealed no effect
      on performance. Control experiments indicated that basic motivational processes
      and general motor responses were intact, such as spontaneous feeding and
      locomotor activity. These results show an essential role for D1-receptor
      activation in both the central nucleus and basolateral complex on the acquisition
      of lever pressing for sucrose pellets in rats, but not the performance of the
      behavior once conditioned. We propose that instrumental learning is dependent on
      plasticity in the central nucleus and basolateral complex amygdala, and that D1
      receptor activation participates in transcriptional processes that underlie this
      plasticity.

PMID- 16111820
TI  - Differential expression of striatal synaptotagmin mRNA isoforms in
      hemiparkinsonian rats.
AB  - Synaptotagmins (Syts) constitute a multi-gene family of 15 putative membrane
      trafficking proteins. The expression of some of the Syts in the brain might be
      dopaminergically controlled and thus affected by dopamine depletion in
      Parkinson's disease. We used hemiparkinsonian rats to investigate the effects of
      chronic striatal dopamine depletion and the acute effects of antiparkinsonic drug
      L-DOPA or D1 agonist (+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine hydrobromide (SKF82958) on the levels of striatal Syt
      I, II, IV, VI, VII, X, XI mRNA isoforms. On the 6-hydroxydopamine (6-OHDA)
      lesioned side we observed a nearly total loss of tyrosine hydroxylase (TH),
      synaptotagmin I, Syt IV, Syt VII and Syt XI mRNA levels in the substantia nigra
      compacta (SNc). In dopamine-depleted striatum we also found a significant down
      regulation Syt II and up-regulation of Syt X mRNA levels that could not be
      reversed by the acute treatment either with L-DOPA or SKF82958. By contrast,
      these two drugs induced an increase of Syt IV and Syt VII mRNA levels. A time
      course study revealed the highest levels of Syt IV and VII mRNAs to occur at two
      hours and 12 hours after the treatment with SKF82958, respectively. D1 antagonist
      (+/-)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      hydrochloride (SCH23390) but not D2 antagonist haloperidol prevented the L-DOPA
      driven increase of Syt IV and VII mRNAs. These results imply that synaptic
      plasticity in response to chronic striatal dopamine depletion involves a complex
      pattern of changes in striatal Syt mRNA expression. The L-DOPA treatment does not
      reverse the changes in Syt II and Syt X gene expression, but recruits additional,
      D1 receptor-mediated changes in Syt IV and Syt VII gene expression. Whether these
      D1 receptor-mediated changes play a role in the alterations of synaptic
      transmission that results in the unwanted side effects of chronic L-DOPA
      treatment in Parkinson's disease remains to be determined.

PMID- 16111819
TI  - Melanin concentrating hormone innervation of caudal brainstem areas involved in
      gastrointestinal functions and energy balance.
AB  - Neural signaling by melanin-concentrating hormone and its receptor (SLC-1) has
      been implicated in the control of energy balance, but due to the wide
      distribution of melanin-concentrating hormone-containing fibers throughout the
      neuraxis, its critical sites of action for a particular effect have not been
      identified. The present study aimed to anatomically and functionally characterize
      melanin-concentrating hormone innervation of the rat caudal brainstem, as this
      brain area plays an important role in the neural control of ingestive behavior
      and autonomic outflow. Using retrograde tracing we demonstrate that a significant
      proportion (5-15%) of primarily perifornical and far-lateral hypothalamic melanin
      concentrating hormone neurons projects to the dorsal vagal complex. In the caudal
      brainstem, melanin-concentrating hormone-ir axon profiles are distributed densely
      in most areas including the nucleus of the solitary tract, dorsal motor nucleus
      of the vagus, and sympathetic premotor areas in the ventral medulla. Close
      anatomical appositions can be demonstrated between melanin-concentrating hormone
      ir axon profiles and tyrosine hydroxylase, GABA, GLP-1, NOS-expressing, and
      nucleus of the solitary tract neurons activated by gastric nutrient infusion. In
      medulla slice preparations, bath application of melanin-concentrating hormone
      inhibited in a concentration-dependent manner the amplitude of excitatory
      postsynaptic currents evoked by solitary tract stimulation via a pre-synaptic
      mechanism. Fourth ventricular administration of melanin-concentrating hormone (10
      microg) in freely moving rats decreased core body temperature but did not change
      locomotor activity and food and water intake. We conclude that the rich
      hypothalamo-medullary melanin-concentrating hormone projections in the rat are
      mainly inhibitory to nucleus of the solitary tract neurons, but are not involved
      in the control of food intake. Projections to ventral medullary sites may play a
      role in the inhibitory effect of melanin-concentrating hormone on energy
      expenditure.

PMID- 16111821
TI  - 3-Hydroxyglutaric acid moderately impairs energy metabolism in brain of young
      rats.
AB  - 3-Hydroxyglutaric acid (3HGA) accumulates in the inherited neurometabolic
      disorder known as glutaryl-CoA dehydrogenase deficiency. The disease is
      clinically characterized by severe neurological symptoms, frontotemporal atrophy
      and striatum degeneration. Because of the pathophysiology of the brain damage in
      glutaryl-CoA dehydrogenase deficiency is not completed clear, we investigated the
      in vitro effect of 3HGA (0.01-5.0mM) on critical enzyme activities of energy
      metabolism, including the respiratory chain complexes I-V, creatine kinase
      isoforms and Na(+),K(+)-ATPase in cerebral cortex and striatum from 30-day-old
      rats. Complex II activity was also studied in rat C6-glioma cells exposed to
      3HGA. The effect of 3HGA was further investigated on the rate of oxygen
      consumption in mitochondria from rat cerebrum. We observed that 1.0mM 3HGA
      significantly inhibited complex II in cerebral cortex and C6 cells but not the
      other activities of the respiratory chain complexes. Creatine kinase isoforms and
      Na(+),K(+)-ATPase were also not affected by the acid. Furthermore, no inhibition
      of complex II activity occurred when mitochondrial preparations from cerebral
      cortex or striatum homogenates were used. In addition, 3HGA significantly lowered
      the respiratory control ratio in the presence of glutamate/malate and succinate
      under stressful conditions or when mitochondria were permeabilized with
      digitonin. Since 3HGA stimulated oxygen consumption in state IV and compromised
      ATP formation, it can be presumed that this organic acid might act as an
      endogenous uncoupler of mitochondria respiration. Finally, we observed that 3HGA
      changed C6 cell morphology from a round flat to a spindle-differentiated shape,
      but did not alter cell viability neither induced apoptosis. The data provide
      evidence that 3HGA provokes a moderate impairment of brain energy metabolism and
      do not support the view that 3HGA-induced energy failure would solely explain the
      characteristic brain degeneration observed in glutaryl-CoA dehydrogenase
      deficiency patients.

PMID- 16111822
TI  - Overexpression of Bcl-xl protects septal neurons from prolonged hypoglycemia and
      from acute ischemia-like stress.
AB  - Overexpression of Bcl-xl, a member of the Bcl-2 protein family, is reported to
      protect from a variety of stresses involving delayed cell death. We tested the
      ability of Bcl-xl overexpression to protect primary cultures of embryonic rat
      septal neurons subjected to one of four different stresses: 6 h of combined
      oxygen-glucose deprivation, which produces rapid cell death, or a 24 h exposure
      to hypoglycemia, hyperglycemia, or 1mM 3-nitropropionic acid (an inhibitor of
      mitochondrial respiration), which results in a more slowly-developing death.
      Prior to the stress neurons were transiently transfected to overexpress either
      green fluorescent protein only or green fluorescent protein along with wild-type
      Bcl-xl. Immediately after oxygen-glucose deprivation, many neurons expressing
      green fluorescent protein only showed process blebbing and disintegration, with
      only 49% of the initial cells remaining intact with processes. Neurons expressing
      both green fluorescent protein and Bcl-xl showed less damage (68% intact post
      stress, P<0.05). This result indicates that Bcl-xl's saving effects are not due
      solely to blocking delayed (apoptotic) death, because death following oxygen
      glucose deprivation was rapid and was not accompanied by increased activation of
      caspase-3. Bcl-xl expression also significantly protected against the
      hypoglycemic stress (23% intact 24 h post-stress with green fluorescent protein
      only, compared with 70% with Bcl-xl and green fluorescent protein), but did not
      protect from hyperglycemia or 3-nitropropionic acid. Thus Bcl-xl does not protect
      against all forms of delayed death. Bcl-xl's protective effects may include
      blocking early damaging events, perhaps by increasing mitochondrial function in
      the face of low levels of energy substrates. Bcl-xl's protective effects may
      require an intact electron transport chain.

PMID- 16111823
TI  - Effect of streptozotocin-induced diabetes on the gene expression and biological
      activity of 3beta-hydroxysteroid dehydrogenase in the rat spinal cord.
AB  - Abnormal secretion of steroids by the adrenals and gonads is one of the
      disturbances occurring in diabetics but the impact of diabetes on steroid
      formation in the nervous system has never been studied. However, it is well known
      that numerous actions of peripheral steroids on the nervous system require their
      conversion into neuroactive metabolites within the neural tissue. As this in situ
      steroid synthesis/metabolism is crucial for the control of several
      neurobiological functions, we investigated the effects of streptozotocin-induced
      diabetes on the gene expression and activity of 3beta-hydroxysteroid
      dehydrogenase in the spinal cord, a pivotal structure involved in sensorimotor
      and neurovegetative mechanisms. 3beta-Hydroxysteroid dehydrogenase is a key
      enzyme which participates to the biosynthesis of all classes of steroids by
      converting delta5-3beta-hydroxysteroids such as pregnenolone and
      dehydroepiandrosterone into delta4-3-ketosteroids as progesterone and
      androstenedione, respectively. Reverse transcription coupled with quantitative
      real-time polymerase chain reaction revealed that 3beta-hydroxysteroid
      dehydrogenase gene was over-expressed in the spinal cord of streptozotocin
      treated rats compared with controls. Pulse-chase experiments combined with high
      performance liquid chromatography and continuous flow detection of newly
      synthesized steroids showed an increase of 3beta-hydroxysteroid dehydrogenase
      activity responsible for a hyper-production of progesterone in the spinal cord of
      diabetic rats. This up-regulation of progesterone biosynthesis was concomitant
      with a decrease of its transformation into tetrahydroprogesterone, a process
      which facilitated progesterone accumulation in the spinal cord of streptozotocin
      treated rats. Since progesterone is a potent neuroprotective steroid, increase of
      its production appeared as an endogenous molecular and biochemical mechanism
      triggered by spinal nerve cells to cope with degenerative effects of
      streptozotocin-induced diabetes. Our results constitute the first direct evidence
      showing an impact of diabetes on steroid biosynthetic and metabolic pathways in
      the nervous system. The data open new perspectives for the modulation of
      deleterious effects of diabetes by neuroprotective steroids.

PMID- 16111824
TI  - Regulation of mitochondrial uncoupling proteins in mouse inner ear ganglion cells
      in response to systemic kanamycin challenge.
AB  - Mitochondrial uncoupling proteins are a proton transporter family involved in
      regulation mitochondrial superoxide and ATP production. Uncoupling proteins are
      expressed by rat spiral ganglion and vestibular ganglion cells [Hear Res 196
      (2004) 39]. This study tests the hypothesis that uncoupling protein expression is
      up-regulated in response to the reactive oxygen species challenge imposed by
      kanamycin and antioxidant (2,3-dihydroxybenzoate) treatment in mice. In control
      C57BL/6, CBA/J and BALB/c mice, mRNA for uncoupling protein 1, uncoupling protein
      2, uncoupling protein 3, Slc25a27 (uncoupling protein 4) and Slc25a14 (uncoupling
      protein 5/BMCP1) was expressed in the spiral and vestibular ganglia. After
      kanamycin-treatment (700 mg/kg twice daily for 14 days s.c.), uncoupling protein
      2 and uncoupling protein 3 mRNA expression increased significantly in spiral and
      vestibular ganglia and kidney, but was unaffected in cerebral cortex. Significant
      Slc25a27 (uncoupling protein 4) mRNA up-regulation was also observed in spiral
      and vestibular ganglia, but not in kidney or cerebral cortex. These effects were
      blocked by simultaneous administration of kanamycin and 2,3-dihydroxybenzoate
      (300 mg/kg twice daily for 14 days s.c.). Western immunoblotting and
      immunohistochemistry confirmed the uncoupling protein 2 and uncoupling protein 3
      up-regulation in inner ear. Finally, 2,3-dihydroxybenzoate treatment alone
      produced an upregulation of uncoupling protein 1 mRNA in the spiral ganglion,
      vestibular ganglion and cerebral cortex, but not the kidney. Uncoupling protein 2
      and uncoupling protein 3 upregulation in the kidney and inner ear ganglia likely
      reflects their general role as a feedback pathway to reduce mitochondrial
      superoxide generation. Slc25a27 (uncoupling protein 4) upregulation in the inner
      ear ganglia, by contrast, is likely to be a secondary response to kanamycin
      induced hair cell death. We propose that increased uncoupling protein 2,
      uncoupling protein 3 and Slc25a27 expression has several neuroprotective effects
      via reduction in mitochondrial superoxide generation and local thermogenesis,
      including: (1) reducing mean ROS load to prevent apoptosis, (2) increasing signal
      to-noise characteristics of intracellular ROS signaling pathways (e.g.
      lipoxygenases, growth factor and transcription factors), (3) heat-related
      alteration of enzyme kinetics and (4) promotion of cell depolarization
      (activation of heat-gated ion channels).

PMID- 16111825
TI  - D1-like and D2 dopamine receptor antagonists administered into the shell
      subregion of the rat nucleus accumbens decrease cocaine, but not food,
      reinforcement.
AB  - Cocaine self-administration experiments were designed to assess the respective
      roles of D1-like and D2-like dopamine receptors in the ventral forebrain in
      cocaine reinforcement. D1-like or D2-like dopamine receptor antagonists were
      microinjected into the nucleus accumbens core, nucleus accumbens shell,
      neostriatum or lateral septum prior to sessions in which cocaine was self
      administered under a progressive ratio schedule by rats. The results indicated
      that administration of a D1/5 (SCH-23390) or a D2/D3/D4 (eticlopride), but not a
      D3 (U99194A) or D4 (L-750,667), dopamine receptor antagonist into the core and
      shell of the nucleus accumbens decreased the reinforcing efficacy of cocaine.
      However, in control experiments intra-accumbal core administration of SCH-23390
      or eticlopride decreased food self-administration, whereas administration of
      these drugs into the accumbens shell had no effect on food reinforcement. Neither
      SCH-23390 nor eticlopride influenced cocaine reinforcement when administered into
      the neostriatum or lateral septum. Collectively, these results indicate that D1
      like and D2 dopamine receptors in the nucleus accumbens shell selectively
      modulate the reinforcing efficacy of cocaine, whereas D1-like and D2 dopamine
      receptors in the accumbens core have a more general influence on reinforced
      behaviors.

PMID- 16111826
TI  - Potentiation and prolongation of long-term odor memory in neonate rats using a
      phosphodiesterase inhibitor.
AB  - Cyclic AMP has been shown to have a critical role in learning and memory in
      invertebrates. Here we use the rat pup odor preference learning model in which
      odor acts as a conditioned stimulus and beta-adrenoceptor stimulation acts as an
      unconditioned stimulus to test the role of cyclic AMP in an associative mammalian
      paradigm. A phosphodiesterase inhibitor that prevents cyclic AMP breakdown
      (cilomilast) makes a low, learning-ineffective dose of a beta-adrenoceptor
      agonist (isoproterenol, 1mg/kg) an effective unconditioned stimulus in pup odor
      preference learning. A dose of the phosphodiesterase inhibitor (cilomilast, 1
      mg/kg) that induces learning with a weak unconditioned stimulus interferes with
      learning using a normally optimal unconditioned stimulus (isoproterenol, 2
      mg/kg). Cilomilast (3 mg/kg) paired with peppermint odor during learning,
      prolonged memory at least four times longer than without the drug (24 h vs. 96
      h). These data demonstrate a causal role for cyclic AMP in the acquisition and
      duration of odor preference learning in the rat pup.

PMID- 16111827
TI  - Phospholipase A2 activation by melittin enhances spontaneous glutamatergic
      excitatory transmission in rat substantia gelatinosa neurons.
AB  - In order to know a role of phospholipase A2 in modulating nociceptive
      transmission, the effect of a secreted phospholipase A2 activator melittin on
      spontaneous glutamatergic excitatory transmission was investigated in substantia
      gelatinosa neurons of an adult rat spinal cord slice by using the whole-cell
      patch-clamp technique. Bath-applied melittin at concentrations higher than 0.5
      microM increased both the amplitude and the frequency of spontaneous excitatory
      postsynaptic current in a manner independent of tetrodotoxin; the latter effect
      of which was examined in detail. In 80% of the neurons examined (n = 64),
      melittin superfused for 3 min gradually increased spontaneous excitatory
      postsynaptic current frequency (by 65+/-6% at 1 microM; n = 51) in a dose
      dependent manner (effective concentration for half-maximal effect = 1.1 microM).
      This effect subsided within 3 min after washout. The spontaneous excitatory
      postsynaptic current frequency increase produced by melittin was reduced by the
      phospholipase A2 inhibitor 4-bromophenacryl bromide (10 microM) while being
      unaffected by the cyclooxygenase inhibitor indomethacin (100 microM) and the
      lipoxygenase inhibitor nordihydroguaiaretic acid (100 microM). A similar increase
      in spontaneous excitatory postsynaptic current frequency was produced by
      exogenous arachidonic acid (50 microM); this effect was also unaffected by the
      cyclooxygenase or lipoxygenase inhibitor. Melittin failed to increase spontaneous
      excitatory postsynaptic current frequency in a nominally Ca2+-free or La3+
      containing Krebs solution. We conclude that melittin increases the spontaneous
      release of L-glutamate to substantia gelatinosa neurons by activating secreted
      phospholipase A2 and increasing Ca2+ influx through voltage-gated Ca2+ channels
      in nerve terminals, probably with an involvement of arachidonic acid but not its
      metabolites produced by cyclooxygenase and lipoxygenase. Considering that the
      substantia gelatinosa plays an important role in regulating nociceptive
      transmission, it is suggested that this transmission may be positively modulated
      by secreted phospholipase A2 activation in the substantia gelatinosa.

PMID- 16111828
TI  - Striatal dopamine level increases in the urinary storage phase in cats: an in
      vivo microdialysis study.
AB  - Parkinson's disease is a common neurodegenerative disease that shows not only
      movement disorder, but also profound urinary dysfunction. Bladder hyperactivity
      is the major urodynamic abnormality. Therefore, the basal ganglia have been
      thought to modulate the micturition reflex. In six male adult cats under ketamine
      anesthesia, in which spontaneous isovolumetric micturition reflexes had been
      generated, we measured levels of striatal dopamine, in micturition and storage
      phases, using in vivo microdialysis. The striatal dopamine level significantly
      increased in the storage phase as compared with that in the micturition phase. It
      is suggested that striatal dopamine may inhibit the micturition reflex via the
      dopamine D1 receptor-GABAergic direct striatal output pathway, and that
      disruption of this pathway may be what leads to bladder hyperactivity in patients
      with Parkinson's disease.

PMID- 16111830
TI  - Gene dosage-dependent transmitter release changes at neuromuscular synapses of
      CACNA1A R192Q knockin mice are non-progressive and do not lead to morphological
      changes or muscle weakness.
AB  - Ca(v)2.1 channels mediate neurotransmitter release at the neuromuscular junction
      (NMJ) and at many central synapses. Mutations in the encoding gene, CACNA1A, are
      thus likely to affect neurotransmitter release. Previously, we generated mice
      carrying the R192Q mutation, associated with human familial hemiplegic migraine
      type-1, and showed first evidence of enhanced presynaptic Ca(2+) influx [Neuron
      41 (2004) 701]. Here, we characterize transmitter release in detail at mouse
      R192Q NMJs, including possible gene-dosage dependency, progression of changes
      with age, and associated morphological damage and muscle weakness. We found, at
      low Ca(2+), decreased paired-pulse facilitation of evoked acetylcholine release,
      elevated release probability, and increased size of the readily releasable
      transmitter vesicle pool. Spontaneous release was increased over a broad range of
      Ca(2+) concentrations (0.2-5mM). Upon high-rate nerve stimulation we observed
      some extra rundown of transmitter release. However, no clinical evidence of
      transmission block or muscle weakness was found, assessed with electromyography,
      grip-strength testing and muscle contraction experiments. We studied both adult (
      approximately 3-6 months-old) and aged ( approximately 21-26 months-old) R192Q
      knockin mice to assess effects of chronic elevation of presynaptic Ca(2+) influx,
      but found no additional or progressive alterations. No changes in NMJ size or
      relevant ultrastructural parameters were found, at either age. Our
      characterizations strengthen the hypothesis of increased Ca(2+) flux through
      R192Q-mutated presynaptic Ca(v)2.1 channels and show that the resulting altered
      neurotransmitter release is not associated with morphological changes at the NMJ
      or muscle weakness, not even in the longer term.

PMID- 16111829
TI  - Differential involvement of p38 and JNK MAP kinases in HIV-1 Tat and gp120
      induced apoptosis and neurite degeneration in striatal neurons.
AB  - The role of p38 and c-jun-N-terminal kinases 1/2, members of the mitogen
      activated protein kinase family, in mediating the toxic effects of human
      immunodeficiency virus-1 transactivator of transcription (Tat) and gp120 were
      explored in primary mouse striatal neurons in vitro. Both Tat and gp120 caused
      significant increases in p38 and c-jun-N-terminal kinase mitogen-activated
      protein kinase phosphorylation, caspase-3 activity, neurite losses and cell death
      in striatal neurons. Tat-induced increases in caspase-3 activity were
      significantly attenuated by an inhibitor of c-jun-N-terminal kinase (anthra[1,9
      cd]pyrazol-6(2H)-one), but not by an inhibitor of p38 ([4-(4-fluorophenyl)-2-(4
      methylsul-finylphenyl)-5-(4-pyridyl)1 H-imidazole]), mitogen-activated protein
      kinase. However, despite preventing increases in caspase-3 activity, c-jun-N
      terminal kinase inhibition failed to avert Tat-induced neuronal losses suggesting
      that the reductions in caspase-3 activity were insufficient to prevent cell death
      caused by Tat. Alternatively, gp120-induced increases in caspase-3 activity,
      neurite losses and neuronal death were prevented by p38, but not c-jun-N-terminal
      kinase, mitogen-activated protein kinase inhibition. Our findings suggest that
      gp120 induces neuronal dysfunction and death through actions at p38 mitogen
      activated protein kinase, while Tat kills neurons through actions that are
      independent of p38 or c-jun-N-terminal kinase mitogen-activated protein kinase,
      or through the concurrent activation of multiple proapoptotic pathways.

PMID- 16111831
TI  - Interactions among mu- and delta-opioid receptors, especially putative delta1-
      and delta2-opioid receptors, promote dopamine release in the nucleus accumbens.
AB  - The effect of interactions among mu- and delta-opioid receptors, especially the
      putative delta(1)- and delta(2)-opioid receptors, in the nucleus accumbens on
      accumbal dopamine release was investigated in awake rats by in vivo brain
      microdialysis. In agreement with previous studies, perfusion of the nucleus
      accumbens with the mu-, delta(1)- and delta(2)-opioid receptor agonists [D
      Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), [D-Pen(2,5)]-enkephalin (DPDPE)
      and [D-Ser(2)]Leu-enkephalin-Thr(6), respectively, significantly enhanced the
      extracellular amount of accumbal dopamine in a dose-related manner (5.0 nmol and
      50.0 nmol). However, the highest concentration tested (50.0 nmol) of DAMGO
      induced a biphasic effect, i.e. a rapid onset increase lasting for 75 min
      followed by a slower onset gradual and prolonged increase. The mu-opioid receptor
      antagonist D-Phe-Cys-Tyr-d-Trp-Orn-Thr-Phe-Thr-NH(2) (0.15 nmol) primarily
      reduced the DAMGO-induced second component. The delta(1)-opioid receptor
      antagonist (E)-7-benzylidenenaltrexone (0.15 nmol) significantly reduced the
      first component and abolished the second component induced by DAMGO, while the
      delta(2)-opioid receptor antagonist naltriben (1.5 nmol) significantly reduced
      only the first component. The DPDPE (50.0 nmol)-induced dopamine increase was
      almost completely abolished by (E)-7-benzylidenenaltrexone, but only partially
      reduced by D-Phe-Cys-Tyr-d-Trp-Orn-Thr-Phe-Thr-NH(2) and naltriben. The [D
      Ser(2)]Leu-enkephalin-Thr(6) (50.0 nmol)-induced dopamine increase was almost
      completely abolished by naltriben, but not at all by D-Phe-Cys-Tyr-d-Trp-Orn-Thr
      Phe-Thr-NH(2) and (E)-7-benzylidenenaltrexone. The non-selective opioid receptor
      antagonist naloxone (0.75 and 1.5 nmol) dose-dependently reduced the effects of
      DAMGO, DPDPE and [D-Ser(2)]Leu-enkephalin-Thr(6) but only to about 10-25% of the
      control values. Moreover, perfusion with the sodium channel blocker tetrodotoxin
      (0.1 nmol) reduced the DAMGO-induced dopamine increase by 75%, while it almost
      completely abolished the increase induced by DPDPE or [D-Ser(2)]Leu-enkephalin
      Thr(6). The results show that stimulation of mu-opioid receptors or, to a lesser
      degree, delta(1)-opioid receptors results in a large naloxone-sensitive increase
      and a small naloxone-insensitive increase of extracellular dopamine. It is
      suggested that the naloxone-insensitive component is also tetrodotoxin
      insensitive. Furthermore, it is hypothesized that stimulation of mu-opioid
      receptors activates delta(1)-receptors, which in turn activate delta(2)-opioid
      receptors, thereby giving rise to a rapid onset increase of extracellular
      dopamine. In addition, it is hypothesized that stimulation of another group of mu
      opioid receptors activates a second group of delta(1)-opioid receptors that is
      not coupled to delta(2)-opioid receptors and mediates a slow onset increase of
      extracellular dopamine. Finally, it is suggested that stimulation of delta(1)- or
      delta(2)-opioid receptors inhibits mu-opioid receptors involved in the slow onset
      increase in extracellular dopamine, whereas stimulation of delta(1)-, but not
      delta(2)-, opioid receptors is suggested to activate mu-opioid receptors involved
      in the rapid increase in extracellular dopamine.

PMID- 16111832
TI  - Does stage-of-change predict dropout in a culturally diverse sample of
      adolescents admitted to inpatient substance-abuse treatment? A test of the
      Transtheoretical Model.
AB  - The Transtheoretical Model (TTM) () proposes that the stages-of-change construct
      can serve as useful tool for identifying those most at-risk of treatment dropout
      [Prochaska, J. O. (1999). How do people change, and how can we change to help
      many more people? In M. A. Hubble, B. L. Duncan, & S. D. Miller (Eds.), The heart
      and soul of change (pp. 227-255). Washington: American Psychological
      Association]. While researchers have found mixed support for this claim in adult
      samples, studies have not yet tested this issue in adolescent substance-abuse
      treatment settings. This paper reports findings from a Canadian study of
      adolescents (n = 130: 80 Caucasians, 50 Aboriginals) admitted to a hospital
      based, residential substance-abuse treatment program. Two approaches were used to
      test the TTM's claim: (1) a hierarchical logistic regression model of dropout was
      developed using the subscales of the University of Rhode Island Change Assessment
      instrument (URICA), demographic variables, and subscales of the Addiction
      Severity Index (ASI); and (2) a chi-square analysis was employed to test the
      hypothesized relation between stage-of-change and dropout status. The findings
      demonstrated that the best predictive model of dropout included only the
      Precontemplation subscale of the URICA (OR: 4.3; 95% CI: 2.0-9.0). In addition,
      adolescents assigned to the Precontemplation stage manifested significantly
      higher rates of treatment attrition than individuals in the Contemplation or
      Preparation/Action stages. This study provides important empirical support for
      the predictive utility of the stage-of-change construct among a culturally
      diverse sample of adolescents admitted to an inpatient substance-abuse treatment
      program.

PMID- 16111833
TI  - The drinking situations of adolescents treated for alcohol use disorders: a
      psychometric and alcohol-related outcomes investigation.
AB  - Psychometric properties of the Inventory of Drinking Situations (IDS) were
      examined using a sample of adolescents with Alcohol Use Disorders (AUDs; N = 352;
      mean age=16.6; 65.6% boys). Relations of drinking situations to alcohol-related
      outcomes 1 and 3 years following treatment also were investigated. Consistent
      with the higher-order structure of the IDS reported in adult samples, findings
      indicated that a 3 factor solution provided the best fit to the data: Negative
      (alpha = .98), Social (alpha = .95), and Temptation (alpha = .84) Situations.
      With regard to convergent and discriminate validity, evidence suggested that the
      Negative Situations subscale was related more strongly to an indicator of
      negative emotionality than to an indicator behavioral undercontrol. Conversely,
      the Social Situations subscale was associated more strongly with an indicator of
      behavioral undercontrol than an indicator of negative emotionality. Social and
      temptation drinking situations were associated with alcohol-related outcomes 1
      year following treatment, but this was generally not the case 3 years following
      treatment. These results indicate that the IDS is a reliable and valid measure
      for use with adolescents receiving treatment for alcohol-related problems.

PMID- 16111834
TI  - Facilitating youth self-change through school-based intervention.
AB  - Early interventions for youth with high rates of alcohol use have often suffered
      from lack of willing participation due to negative stereotypes about treatment
      and the impression that alcohol interventions are not developmentally relevant
      for adolescents. This study evaluated the effectiveness of a school-based
      voluntary secondary intervention for alcohol use (Project Options). 1254 high
      school students (55% girls; M age = 15.9, SD = 1.2) with a history of lifetime
      drinking completed survey measures after the first year of Project Options in 3
      schools. These results suggest that the intervention was successful in recruiting
      high-frequency drinkers into the intervention as well as facilitating attempts to
      cut down or quit alcohol use in this group of adolescents. This study provides
      preliminary support for a consumer-based approach to alcohol intervention and
      design and use of voluntary secondary interventions in a school-based population.

PMID- 16111835
TI  - Self-management of psychiatric symptoms using over-the-counter (OTC)
      psychopharmacology: the S-DTM therapeutic model--Self-diagnosis, self-treatment,
      self-monitoring.
AB  - Pharmacological self-management is becoming more widespread in modernizing
      societies, as part of a general expansion of health care. This may exert a vital
      corrective balance to the professionalization of health by ensuring that the
      individual perspective of patients is not neglected. There are many 'good ideas'
      for new treatments being published which have a plausible scientific rationale
      for effectiveness and a low likelihood of harm, yet are essentially ignored by
      mainstream medical research. The most likely avenue for progress is probably the
      spread of self-management, together with increased sharing of experience via the
      internet. There is considerable scope for self-management of psychiatric symptoms
      with psychoactive medication purchased 'over-the-counter' (OTC) and without
      prescription. A surprisingly wide range of effective psychoactive agents are
      available with the potential to self-treat many of the common psychiatric
      problems. These include 'medical' psychopharmacological agents such as analgesics
      and antihistamines, a plant extract called St. John's Wort (Hypericum), and
      physical treatments such as early morning bright light therapy. But self
      management currently lacks an explicit therapeutic model. A three stage process
      of S-DTM - self-diagnosis, self-treatment and self-monitoring is proposed and
      described in relation to psychiatric symptoms. Self-diagnosis describes the skill
      of introspection to develop awareness of inner bodily states and emotions. A
      specific sensation is identified and isolated as the 'focal symptom' for
      subsequent treatment and monitoring. Self-treatment involves choosing a drug (or
      other therapy) which is intended to alleviate the focal symptom. Self-monitoring
      entails a continued awareness of the focal system and of general well-being in
      order to evaluate effect of therapy. Self-monitoring could involve repeated
      cycles of dose-adjustment, and on-off ('challenge-dechallenge-rechallenge')
      therapeutic trials. An example of S-DTM applied to psychiatry might include the
      attempt to alleviate the fatigue and malaise symptoms underlying a 'depressed'
      mood by using OTC analgesics such as aspirin, paracetamol/acetaminophen,
      ibuprofen or codeine. Anxiety symptoms might be self-managed either using an
      'unofficial SSRI' (selective serotonin-reuptake inhibitor) such as the
      antihistamines diphenhydramine or chlorpheniramine; or with St John's
      Wort/hypericum.

PMID- 16111836
TI  - Transcriptional regulation of the S-layer protein type I secretion system in
      Caulobacter crescentus.
AB  - The Gram-negative Caulobacter crescentus exports RsaA, the crystalline S-layer
      subunit protein using a dedicated type I secretion system. The protein and two
      transporter genes (rsaADE) are located together, comparable to the Escherichia
      coli type I hemolysin hlyCABD operon, where read through of a stem loop following
      hlyCA results in reduced transcription of the hlyBD. Using two genetic approaches
      and a direct assessment of transcription from regions 5' to the genes we learned
      that rsaD and rsaE were transcribed together as a separate transcript from rsaA.
      These results are contrary to previous assumptions about the rsaADE type I
      secretion gene control and add another theme to the area of type I secretion
      transcription regulation. It may be that to accommodate the high levels of RsaA
      secretion, the type I transporters must be transcribed independently from rsaA.

PMID- 16111837
TI  - Non-coding RNAs: new players in eukaryotic biology.
AB  - The completion of the human, mouse and other eukaryotic genomes were important
      scientific milestones, but they were just small steps towards the understanding
      of eukaryotic biology. Recent transcriptome analysis and different experimental
      approaches have identified a surprisingly large number of non-coding RNAs
      (ncRNAs) in eukaryotic cells. ncRNAs comprise microRNAs, anti-sense transcripts
      and other Transcriptional Units containing a high density of stop codons and
      lacking any extensive "Open Reading Frame". They have been shown to regulate gene
      expression by novel mechanisms such as RNA interference, gene co-suppression,
      gene silencing, imprinting and DNA demethylation. It is becoming clear that these
      novel RNAs perform critical functions during development and cell
      differentiation. There is also mounting evidence of their involvement in cancer
      and neurological diseases. Together, all this information indicates that ncRNAs
      are emerging as a new class of functional transcripts in eukaryotes. Therefore,
      great challenges lie in the years ahead: understanding the molecular biology of
      higher organisms will require revealing all proteins (Proteome), all ncRNAs
      (RNome) and their interactions (Interactome) in the complex molecular scenario
      within eukaryotic cells.

PMID- 16111838
TI  - Selenite-induced apoptosis of osteoclasts mediated by the mitochondrial pathway.
AB  - The possible effects of sodium selenite on mature osteoclasts were investigated.
      Incubation of osteoclast-like cells differentiated from RAW 264.7 cells with
      sodium selenite induced apoptosis as revealed by morphological changes,
      internucleosomal DNA fragmentation, and activation of caspase-3. Selenite also
      induced generation of the superoxide anion and reduced the number of free thiol
      groups in the osteoclast-like cells, suggestive of a shift to a more oxidizing
      intracellular environment. In addition, selenite induced protein aggregation by
      thiol cross-linking, loss of the mitochondrial membrane potential, and cytochrome
      c release in mitochondria isolated from the osteoclast-like cells. Finally,
      selenite-induced DNA fragmentation in osteoclasts was inhibited both by
      cyclosporin A, a blocker of the mitochondrial permeability transition pore, and
      by DEVD-CHO, a cell-permeable inhibitor of caspase-3. These results thus suggest
      that selenite induces apoptosis mediated by the mitochondrial pathway in mature
      osteoclasts.

PMID- 16111839
TI  - Effects of toluene on seizures induced by convulsants acting at distinct ligand
      gated ion channels.
AB  - Toluene is one of the most widely used solvents. Electrophysiological studies
      indicated that this solvent directly affects various ligand gated ion channels
      including NMDA, GABA(A), nicotinic and glycine receptors. The effect of toluene
      on seizures induced by chemoconvulsants acting on these receptors was compared.
      Mice were pretreated with toluene (100-1000 mg/kg, i.p.) or corn oil followed by
      a timed intravenous infusion of NMDA, bicuculline, picrotoxin, nicotine or
      strychnine to induce seizures. Toluene increased seizure thresholds and lethal
      doses induced by nicotine, NMDA, picrotoxin and bicuculline, but not strychnine
      in the used doses. The relative susceptibility to anticonvulsant effect of
      toluene was in the order: nicotine > NMDA > bicuculline > picrotoxin >
      strychnine. These findings support a unique anticonvulsant profile of toluene and
      suggest that nicotinic and NMDA receptors may be more sensitive than GABA(A) and
      glycine receptors to toluene exposure in seizure-related neural circuits.

PMID- 16111840
TI  - T(H1)-directed modulation of in vitro cytokine production in human peripheral
      blood mononuclear cells by styrene-7.8-oxide.
AB  - Styrene and its chiral main metabolite styrene-7.8-oxide are well characterized
      regarding their cytotoxic, genotoxic and neurotoxic properties. To our knowledge,
      no data exist on the influence of styrene and styrene-7.8-oxide on immune
      reactions. Epidemiological studies suggest that exposure to environmental
      pollutants, specifically volatile organic compounds (VOCs), including styrene is
      one factor contributing to increasing prevalence rates of allergic diseases. In
      this study, we investigated the modulation of the immune system by styrene-7.8
      oxide in vitro. Human peripheral blood mononuclear cells were incubated with
      styrene-7.8-oxide, either as (S)-enantiomer, (R)-enantiomer, or racemic styrene
      7.8-oxide. Subsequently, the secretion of T(H1)-cytokines IFNgamma and IL-12 as
      well as T(H2)-cytokines IL-4 and IL-5 were measured by ELISA. We introduced a
      novel mathematical approach to quantify and compare cytokine responses. The
      results revealed a stimulation of cytokine secretion with emphasis on T(H1)
      cytokines IFNgamma and IL-12. The stimulating effects were elicited at
      concentrations of styrene-7.8-oxide comparable to what would be encountered at
      industrial workplaces where styrene is processed. Therefore, we conclude that
      styrene-7.8-oxide exhibits immunomodulating capacities, which can be of clinical
      relevance for individuals with high styrene exposure.

PMID- 16111841
TI  - Diabetogenic effects and pancreatic oxidative damage in rats subchronically
      exposed to arsenite.
AB  - Recent epidemiologic studies have associated chronic inorganic arsenic ((i)As)
      exposure with an increase in the prevalence of diabetes mellitus. Currently, the
      diabetogenic mechanism caused by (i)As exposure is unclear. However, it is
      recognized that (i)As contributes to oxidative stress in several organs and
      systems through generation of reactive oxygen species (ROS). ROS can function as
      signaling molecules to activate a number of cellular stress-sensitive pathways
      linked to insulin resistance and decreased insulin secretion. Male Wistar rats
      were administered sodium arsenite at 1.7 mg/kg (12 h), or water (controls) orally
      for 90 days. At the end of the 90 days of (i)As exposure hyperglycemia,
      hyperinsulinemia and low insulin sensitivity, evaluated by the homeostasis model
      assessment of insulin resistance, was observed. Arsenicals in pancreas of rats
      exposed to (i)As were significantly higher than the control group, being dimethyl
      and trimethyl metabolites the predominant arsenic species. The activity of
      pancreatic thioredoxin reductase was lower than the control group. Also, the
      levels of total glutathione and lipoperoxidation in pancreas increased
      significantly relative to the control group indicating the presence of stress and
      oxidative damage, respectively. These results represent an attempt to establish
      an animal model for in vivo studies of diabetogenic effects of chronic arsenic
      exposure.

PMID- 16111842
TI  - In vitro cytotoxicity assays: comparison of LDH, neutral red, MTT and protein
      assay in hepatoma cell lines following exposure to cadmium chloride.
AB  - The aim of this study was to compare four in vitro cytotoxicity assays and
      determine their ability to detect early cytotoxic events. Two hepatoma cell
      lines, namely HTC and HepG2 cells, were exposed to cadmium chloride (0-300
      microM) for 3, 5 and 8 h. Following exposure to the toxic metal cytotoxicity was
      determined with the lactate dehydrogenase leakage assay (LDH), a protein assay,
      the neutral red assay and the methyl tetrazolium (MTT) assay. In HTC cells no
      toxicity was observed for any incubation period when the LDH leakage, the MTT and
      the protein assay were employed whereas the neutral red assay revealed early
      cytotoxicity starting after incubation of HTC cells with CdCl(2) for 3 h. In the
      case of HepG2 cells the MTT assay reveals cytotoxicity due to CdCl(2) exposure
      after 3 h whereas no such effect is seen with the other three assays. Following 5
      h exposure of HepG2 cells to CdCl(2), toxicity is observed with the MTT assay at
      lower concentrations compared to the ones required for detection of toxicity with
      the LDH leakage and the neutral red assay. In conclusion different sensitivity
      was observed for each assay with the neutral red and the MTT assay being the most
      sensitive in detecting cytotoxic events compared to the LDH leakage and the
      protein assay.

PMID- 16111843
TI  - Determinants of ovarian volume in pre-, menopausal transition, and post
      menopausal women: a population-based study.
AB  - OBJECTIVE: To verify the association of smoking, parity, body mass index, use of
      oral contraceptives, and hormone therapy with ovarian volume in pre-, menopausal
      transition, and post-menopausal women from southern Brazil. METHODS: Cross
      sectional study with 273 women aged 36-62 years, representative of the urban
      population of Passo Fundo, southern Brazil. Participants completed an in-home
      interview and had their anthropometric measurements and ultrasound exams
      performed at a clinical center, using a standardized method. The right and left
      ovaries were measured by ultrasound. Mean ovarian volume was calculated according
      to age, menopausal status, smoking habit, parity, body mass index (BMI), use of
      oral contraceptives (OC), and hormone therapy (HT). RESULTS: Ovarian volume
      decreased after the age of 44 years when adjusted for menopausal status and OC
      use (p = 0.010). The mean ovarian volume decreased with menopausal status
      adjusted for age (p = 0.001) and with current OC use, adjusted for age (p =
      0.001). There was a positive association between ovarian volume and BMI>or=30 in
      every woman adjusted for menopausal status and age (p = 0.005). On the other
      hand, there was no association with smoking, past OC use, and HT. In a linear
      regression model, post-menopause, menopausal transition, age, and BMI were
      significantly and independently associated with ovarian volume. CONCLUSION:
      Ovarian volume decreases with menopausal transition and even more in post
      menopause. The reduction of ovarian volume also occurred with aging and OC use.
      Ovarian volume, however, is positively associated with obesity. Smoking, parity,
      and hormone treatment do not affect ovarian volume in pre-, menopausal
      transition, and post-menopausal women.

PMID- 16111845
TI  - Preparation and characterization of novel fast disintegrating capsules (Fastcaps)
      for administration in the oral cavity.
AB  - The objective of this study was to prepare novel capsule-based fast
      disintegrating dosage forms for the oral cavity (Fastcaps). First, cast films
      were prepared from various additive-containing gelatin solutions and evaluated
      with respect to disintegration time and mechanical properties in order to
      identify suitable formulations for the capsule preparation. The disintegration
      time of films decreased with decreasing bloom strength and could be further
      decreased by the addition of sugars or PEGs. Fast disintegrating capsules were
      successfully prepared by a dipping process, whereby parameters such as the
      viscosity and temperature of the dipping solution and the dipping velocity of the
      steel pins were optimized. The required viscosity range of the dipping solution
      for Fastcap manufacturing was 500-600 cP. The addition of the hydrophilic
      additives (xylitol, sorbitol or PEG 1500) did not significantly affect the
      viscosity and gelation temperature of the dipping solution. The in vitro
      disintegration of Fastcaps (30-45 s) was twice as rapid as the one of regular
      hard gelatin capsules. In vivo, Fastcaps disintegrated rapidly (9-13 s) and their
      content was spread throughout the oral cavity within seconds. Lactose and/or
      microcrystalline cellulose were suitable fillers for Fastcaps. The mechanical
      properties of Fastcaps were similar to commercially available gelatin capsules,
      which assures good processability and handling.

PMID- 16111844
TI  - Effect of nonylphenol ethoxylates (NPEs) on barrier functions of epithelial cell
      membranes: opening of tight junctions and competitive inhibition of P-gp-mediated
      efflux.
AB  - The effect of nonylphenol ethoxylates (NPEs) on selected barrier functions of
      biological membranes, such as tight junction and P-gp efflux pump of epithelial
      membranes, against the transport of xenobiotics was examined. The Caco-2 cell
      line was used to evaluate the transport of mannitol and daunomycin across the
      cell monolayer as well as the cellular uptake of daunomycin. In the presence of
      NPEs, the transport of mannitol was increased, with NP-9 showing a maximal
      effect, and the transepithelial electrical resistance (TEER) was reduced. The
      onset of this effect of NP-9 was fairly rapid and reversible for a short term
      (e.g., 2 h) treatment, while irreversible for a long term (e.g., 72 h) treatment.
      In the presence of NP-9, the apical uptake of daunomycin was increased,
      suggesting competitive inhibition between NP-9 and daunomycin in the efflux via
      the P-gp system. However, a 72 h pretreatment of the cells with NP-9 (up to 1000
      nM) did not affect the apparent cellular uptake of daunomycin, suggesting no
      significant effect of NPEs on the expression of P-gp. In conclusion, NPEs appear
      to rapidly open the tight junction of epithelial cell membranes and to
      competitively inhibit the efflux of P-gp substrates, thereby reducing the self
      protection ability of the organism against xenobiotics or hazardous environmental
      compounds that are transported via the paracellular pathway (i.e., uptake) or the
      P-gp system (i.e., efflux).

PMID- 16111846
TI  - Oligo- and polysaccharides exhibit a structure-dependent bioactivity on human
      keratinocytes in vitro.
AB  - In traditional medicine, a variety of plants with high carbohydrate contents were
      used for dermatological therapies. Contemporary investigations confirmed
      exogenous carbohydrates as biologically active. The recent study describes the
      characterization of oligo- and polysaccharides from medicinal herbs and
      evaluation of composite-dependent physiological activity of carbohydrates on
      human keratinocytes in vitro. Polysaccharide isolation was followed by size- and
      charge fractionation. Identification of monosaccharide components was performed
      by GLC/MS. Primary human keratinocytes (NHK) and cells of the cell line HaCaT
      were used for investigation of carbohydrate action on cellular proliferation
      (BrdU-uptake), differentiation specific enzymes (involucrin), cell viability (MTT
      reduction) and cytotoxicity. Incubation of keratinocytes with a purified beta
      glucan from Reed mace seeds resulted in an improved proliferation followed by an
      increased differentiation after contact inhibition. Fucosylated oligo- and
      polysaccharides of human milk and Sea weed induced involucrin expression as maker
      for early differentiation without an increase in proliferation. Cell viability
      and proliferation of keratinocytes were enhanced by an arabinogalactan of Kaki
      fruits. Okra fruit rhamnogalacturonans increased cell proliferation. Heart sease
      pectin-like polysaccharides reduced the proliferation significantly but improved
      the cell viability. These results led assume that the carbohydrates of
      traditional used herbs play a part in their efficacy.

PMID- 16111847
TI  - Population data for Y-chromosome STR haplotypes from Piedmont (Italy).
AB  - Eight Y-chromosome STR loci (DYS19, DYS389-I, DYS389-II, DYS390, DYS391, DYS392,
      DYS393 and DYS385) were analysed in a sample of 236 unrelated males from four
      towns of Piedmont (Trino, Biella, Cavaglia, Postua). One hundred and fifty six
      different haplotypes were observed and 55 of them were not previously observed in
      the Y-STR Haplotype Reference Database (http://www.ystr.org/).

PMID- 16111849
TI  - Use of porous graphitic carbon column for the separation of natural isomeric
      tropane alkaloids by capillary LC and mass spectrometry.
AB  - This study presents the outstanding chromatographic selectivity of a porous
      graphitic carbon support for the separation of four isomeric tropane alkaloids
      from the stem-bark of Schizanthus grahamii (Solanaceae). Capillary liquid
      chromatography coupled to mass spectrometry was studied after the appropriate
      selection of mobile phase composition, temperature, nature and concentration of
      the acidic modifier. Fragmentation behaviour by in-source collision-induced
      dissociation (CID) on a single quadrupole mass spectrometer, or MSn with an ion
      trap, was investigated for structural identification. The ability to
      differentiate the isomers by in-source CID was demonstrated and a fragmentation
      pathway, based on MSn sequences together with accurate mass experiments, was
      proposed.

PMID- 16111848
TI  - A simple spectrophotometric method for the determination of beta-blockers in
      dosage forms.
AB  - A simple, extraction-free spectrophotometric method is proposed for the analysis
      of some beta-blockers, namely atenolol, timolol and nadolol. The method is based
      on the interaction of the drugs in chloroform with 0.1% chloroformic solutions of
      acidic sulphophthalein dyes to form stable, yellow-coloured, ion-pair complexes
      peaking at 415 nm. The dyes used were bromophenol blue (BPB), bromothymol blue
      (BTB) and bromocresol purple (BCP). Under the optimum conditions, the three drugs
      could be assayed in the concentration range 1-10 microg ml(-1) with correlation
      coefficient (n = 5) more than 0.999 in all cases. The stoichiometry of the
      reaction was found to be 1:1 in all cases and the conditional stability constant
      (K(F)) of the complexes have been calculated. The free energy changes (DeltaG)
      were determined for all complexes formed. The interference likely to be
      introduced from co-formulated drugs was studied and their tolerance limits were
      determined. The proposed method was then applied to dosage-forms the percentage
      recoveries ranges from 99.12-100.95, and the results obtained were compared
      favorably with those given with the official methods.

PMID- 16111850
TI  - Analytical methods for assay of ellagic acid and its solubility studies.
AB  - Ultra-violet (UV) spectrophotometric and high performance liquid chromatographic
      methods for quantitative determination of ellagic acid (EA), an antioxidant were
      developed. The analytical methods were validated for linearity, accuracy, intra-
      and inter-day variability, and precision. EA was eluted using a polyethylene
      glycol (PEG) column with mobile phase composed of acetonitrile and 5 mM potassium
      dihydrogen orthophosphate buffer pH 2.5 (80:20, v/v). The UV and high performance
      liquid chromatography (HPLC) methods have lower detection limits of 0.2 and 0.1
      microg/ml, respectively. Because of the increasing pharmaceutical interest in
      phytochemicals and their solubility problems, solubility studies for EA were also
      carried out. Various organic solvents and surfactants were screened for assessing
      solubility of EA and the compound was found to be soluble in some
      pharmaceutically acceptable solvents like triethanolamine, polyethylene glycol
      400 and N-methyl pyrrollidone (NMP). Aqueous and pH dependent solubility of EA
      were determined using UV and HPLC methods, respectively.

PMID- 16111851
TI  - A selective HPLC method for the determination of indapamide in human whole blood:
      application to a bioequivalence study in Chinese volunteers.
AB  - Indapamide was extracted from human whole blood with diethyl ether and was
      determined by a HPLC-UV method using an Inertsil ODS-3 column and an isocratic
      mobile phase consisting of 55% buffer solution (2 g KH(2)PO(4), 3 ml H(3)PO(4)
      and 3.5 ml triethylamine in 1l of H(2)O), 40% acetonitrile and 5% methanol for
      12.5 min, and then a gradient flush from 100% isocratic to a mixture of 20%
      isocratic mobile phase and 80% methanol for 3 min. Indapamide and glipizide
      (internal standard) were eluted from the column at about 10.5 and 12.8 min,
      respectively. The method had within day precision values in the range +/- 1.2 to
      +/- 9.7% (n = 5) and between day precision in the range +/- 3.3 to +/- 9.7%. The
      method was linear over the range of 10-400 ng/ml of indapamide in blood (R =
      0.999). The LOQ (s/n = 10) of the method was 10 ng/ml. The method was applied in
      a study of the pharmacokinetics and bioequivalence of generic indapamide capsules
      (2.5 mg) in comparison with reference indapamide tablets (2.5mg), in 20 healthy
      male Chinese volunteers. The mean values of major pharmacokinetic parameters of
      C(max), AUC(0-48), AUC(0-infinity), T(max), and t(1/2) of indapamide in healthy
      male Chinese volunteers after po a single 5 mg dose for the test product were
      331.0 +/- 39.2 ng/ml, 6,193.7+/-873.5 ng h/ml, 7311.8+/-1,232.3 ng h/ml, 3.2+/
      0.9h, and 17.3+/-2.8 h, respectively. There was no significant differences
      between the two formulations.

PMID- 16111852
TI  - Synthetic polymers as biomacromolecular models for studying ligand-protein
      interactions: a nuclear spin relaxation approach.
AB  - In this paper, we applied an NMR methodology based on the analysis of selective
      spin-lattice relaxation rate enhancements of ligand protons induced by
      interaction processes between prednisolone and a synthetic copolymer, namely
      poly(N-isopropylacrylamide-co-N-acryloil-L-phenylalanine), in order to
      investigate this system as a model for studying drug-biomacromolecules
      interactions. The contribution from the bound ligand fraction to the observed
      relaxation rate in relation to macromolecule concentration allowed the
      calculation of the normalized affinity index [A(N)(I)](T)(L), in which the
      effects of motional anisotropies and different proton densities have been
      removed. This parameter, which represents the global affinity of the ligand
      towards the macromolecule, isolates the contribution due to a decrease in the
      ligand dynamics caused by the binding with the copolymer. The affinity index
      calculated for prednisolone-copolymer complex compared to that obtained for
      prednisolone-albumin system, suggested that synthetic polymers as models of
      biomacromolecules can play an important role in drug-protein interaction studies.

PMID- 16111853
TI  - Solid-phase extraction and liquid chromatography-electrospray mass spectrometric
      analysis of saponins in a Chinese patent medicine of formulated Salvia
      miltiorrhizae and Panax notoginseng.
AB  - In this paper, a method using solid-phase extraction (SPE) and HPLC/ESI-MS(n) for
      the identification of the major saponins in "Danshen Dripping Pill", a Chinese
      patent medicine consisting of Salvia miltiorrhizae and Panax notoginseng, is
      described. Through solid-phase extraction process, the saponins in "Danshen
      Dripping Pill" were separated from the phenolic constituents of S. miltiorrhizae
      and, meanwhile, efficiently concentrated. Subsequently, these saponins were
      characterized by HPLC/ESI-MS(n) analysis. Based on the studies of MS and MS2
      spectra and the comparison with reference compounds and literature data, a total
      of 19 saponins were identified.

PMID- 16111854
TI  - Macrophages accumulate in the early phase of tendon-bone healing.
AB  - A scar tissue interface forms rather than a normal ligament insertion site
      following attachment of a tendon graft to bone. The specific cell types that
      initiate the process of tendon-to-bone healing are unknown. We hypothesized that
      inflammatory cell accumulation following tendon-to-bone repair results in this
      scar interface. We used a rodent model to examine the temporal and spatial
      pattern of accumulation of hematopoietic lineage cells in the early phase of
      tendon-to-bone healing. Thirty-six Lewis rats underwent anterior cruciate
      ligament (ACL) reconstruction in the left knee using a flexor digitorum longus
      tendon graft. Six animals were sacrificed at 4, 7, 11, 14, 21, and 28 days after
      surgery. Serial sections were analyzed for proliferating cells (PCNA), recruited
      macrophages (ED1), resident macrophages (ED2), neutrophils, T-lymphocytes (CD3),
      mast cells, immature progenitor cells/pericytes (expressing the NG2 cell-surface
      chondroitin sulfate proteoglycan), and newly-formed blood vessels (Factor VIII).
      Neutrophils, ED1(+) and ED2(+) macrophages accumulated sequentially in the
      healing tendon graft, with progressive cell ingrowth from the interface towards
      the inner tendon. Neutrophils and ED1(+) cells were seen in the tendon-bone
      interface at 4 days after surgery, while ED2(+) macrophages were not identified
      until 11 days. These cells progressively repopulated the tendon graft. NG2
      positive progenitor cells were found along the edge of the bone tunnel in the
      interface, but these cells did not invade the tendon. Occasional T-lymphocytes
      and mast cells were seen in the tendon-bone interface. There was no proliferation
      of intrinsic tendon cells, indicating that the tendon does not directly
      contribute to healing. We hypothesize that cytokines produced by infiltrating
      macrophages are likely to contribute to the formation of a fibrous scar tissue
      interface rather than a normal insertion site.

PMID- 16111856
TI  - Should the Retention trial of the Test of Memory Malingering be optional?
AB  - The present study examined the false negative error rate associated with the
      optional use of the Retention trial the Test of Memory Malingering (TOMM). TOMM
      scores from 150 traumatic brain injury and 150 chronic pain patients were
      examined. Results indicated that early termination of the TOMM resulted in 3% of
      patients going undetected by the TOMM. The practical cost of this error was
      minimized by the inclusion of at least one other SVT. Clinical implications are
      discussed.

PMID- 16111855
TI  - Morbidity and mortality rates following gastric cancer surgery and contiguous
      organ removal, a population based study.
AB  - BACKGROUND: Complete surgical (R0) resection remains the only potentially
      curative intervention for patients with localised gastric cancer. To achieve a
      curative resection, patients may require complex operations with resection of
      contiguous organs. The aim of this study was to assess how the extent of surgical
      resection influenced morbidity, mortality and survival in an aged non-selected
      population with significant comorbid disease. PATIENTS AND METHODS: Data were
      extracted from the Scottish Audit of Gastric and Oesophageal Cancer (SAGOC), a
      prospective population-based audit of all oesophageal and gastric cancers in
      Scotland between 1997 and 1999 with a minimum of 1-year follow-up. RESULTS: A
      total of 646 patients underwent surgical exploration for gastric cancer. A
      significantly higher incidence of chest infections (18.5 vs 11%, p< 0.05) and
      anastomotic leaks (14.3 vs 2.2%, p< 0.05) were associated with total gastrectomy
      (n=168) when compared to distal gastrectomy (n=272) resections. A 9.2% mortality
      rate and a 60% 1-year survival were associated with gastric resection alone.
      Removal of the spleen (n=131), pancreas (n=30) or liver resection (n=5) was
      associated with a significantly higher mortality rates, 18.3, 23.3 and 40%,
      respectively (p< 0.05), and significantly lower 1-year survival rates, 50.9, 39.1
      and 20%, respectively (p< 0.05). CONCLUSIONS: The risk of more extensive
      resection is not balanced by improved survival in this population based series.
      Extending gastric resection to involve contiguous organs should be confined to
      highly selected cases.

PMID- 16111857
TI  - A high-resolution comparative map between pig chromosome 17 and human chromosomes
      4, 8, and 20: identification of synteny breakpoints.
AB  - We report on the construction of a high-resolution comparative map of porcine
      chromosome 17 (SSC17) focusing on evolutionary breakpoints with human
      chromosomes. The comparative map shows high homology with human chromosome 20 but
      suggests more limited homologies with other human chromosomes. SSC17 is of
      particular interest in studies of chromosomal organization due to the presence of
      QTLs that affect meat quality and carcass composition. A total of 158 pig ESTs
      available in databases or developed by the Sino-Danish Pig Genome Sequencing
      Consortium were mapped using the INRA-University of Minnesota porcine radiation
      hybrid panel. The high-resolution map was further anchored by fluorescence in
      situ hybridization. This study confirmed the extensive conservation between SSC17
      and HSA20 and enabled the gene order to be determined. The homology of the SSC17
      pericentromeric region was extended to other human chromosomes (HSA4, HSA8) and
      the chromosomal breakpoint boundaries were accurately defined. In total 15
      breakpoints were identified.

PMID- 16111858
TI  - Event-related potentials in cocaine-exposed children during a Stroop task.
AB  - OBJECTIVE: Prenatal cocaine-exposure may interfere with the ontogeny of
      prefrontal cortical executive functions due to cocaine's effect on the developing
      monoaminergic system. This study presents findings regarding cortical functioning
      in 29 prenatally cocaine-exposed (CE) and non-drug-exposed (NDE) 7- to 9-year-old
      children participating in event related potential (ERP) studies. METHODS: ERPs
      were recorded using 128-electrode high-density arrays while children responded to
      a standard Stroop paradigm. RESULTS: In the Stroop paradigm, CE children
      generated prolonged responses to the words while the NDE children produced
      briefer responses. Effects were noted in the region of the initial positive peak
      (P1), the second negative peak (N2) and the later positive peak (P3).
      CONCLUSIONS: Early cocaine exposure may inhibit the specialization and
      streamlining of brain region involvement during cognitive processing such that
      task processing is slower to begin, requires more diverse cortical involvement,
      and requires more time to complete. ERP methodology has considerable potential
      for studying frontal maturation and may provide additional information to clarify
      generally the specific effects of prenatal CE on cortical functioning and the
      developmental course of cognitive functions.

PMID- 16111859
TI  - Effects of marine algal toxins on thermoregulation in mice.
AB  - Hypothermia is often seen in mice and rats exposed acutely to marine algal
      toxins, but the mechanism of action of these toxins on thermoregulation is not
      well understood. Our laboratory has assessed the thermoregulatory mechanisms of
      two marine algal toxins, maitotoxin and brevetoxin in the mouse. Radiotelemetry
      was used to measure core temperature in the unrestrained mouse while it was
      housed in a temperature gradient allowing the exhibition of thermoregulatory
      behavior. Both maitotoxin (338 ng/kg) and brevetoxin (180 microg/kg) were shown
      to elicit profound hypothermic responses accompanied by a preference for cooler
      ambient temperatures in the gradient. This behavioral response would suggest that
      the toxins alter the central neural control of body temperature, resulting in a
      regulated reduction in body temperature. Following recovery from the acute
      hypothermic effects of brevetoxin, mice developed an elevation in their daytime
      core temperature that persisted for several days after exposure. This fever-like
      response may represent a delayed toxicological effect of the marine algal toxins
      that is manifested through the thermoregulatory system. Overall, algal toxins
      have acute and delayed effects on temperature regulation in the mouse. A better
      understanding of the mechanisms of action of the toxins on thermoregulation
      should lead to improved methods for treating victims of ciguatera and other toxin
      exposures.

PMID- 16111860
TI  - A model of evolution and learning.
AB  - We study a model of evolving populations of self-learning agents and analyze the
      interaction between learning and evolution. We consider an agent-broker that
      predicts stock price changes and uses its predictions for selecting actions. Each
      agent is equipped with a neural network adaptive critic design for behavioral
      adaptation. We discuss three cases in which either evolution or learning, or
      both, are active in our model. We show that the Baldwin effect can be observed in
      our model, viz. originally acquired adaptive policy of best agent-brokers becomes
      inherited over the course of the evolution. We also compare the behavioral
      tactics of our agents to the searching behavior of simple animals.

PMID- 16111861
TI  - Bayesian approach to feature selection and parameter tuning for support vector
      machine classifiers.
AB  - A Bayesian point of view of SVM classifiers allows the definition of a quantity
      analogous to the evidence in probabilistic models. By maximizing this one can
      systematically tune hyperparameters and, via automatic relevance determination
      (ARD), select relevant input features. Evidence gradients are expressed as
      averages over the associated posterior and can be approximated using Hybrid Monte
      Carlo (HMC) sampling. We describe how a Nystrom approximation of the Gram matrix
      can be used to speed up sampling times significantly while maintaining almost
      unchanged classification accuracy. In experiments on classification problems with
      a significant number of irrelevant features this approach to ARD can give a
      significant improvement in classification performance over more traditional, non
      ARD, SVM systems. The final tuned hyperparameter values provide a useful
      criterion for pruning irrelevant features, and we define a measure of relevance
      with which to determine systematically how many features should be removed. This
      use of ARD for hard feature selection can improve classification accuracy in non
      ARD SVMs. In the majority of cases, however, we find that in data sets
      constructed by human domain experts the performance of non-ARD SVMs is largely
      insensitive to the presence of some less relevant features. Eliminating such
      features via ARD then does not improve classification accuracy, but leads to
      impressive reductions in the number of features required, by up to 75%.

PMID- 16111862
TI  - Unifying cost and information in information-theoretic competitive learning.
AB  - In this paper, we introduce costs into the framework of information maximization
      and try to maximize the ratio of information to its associated cost. We have
      shown that competitive learning is realized by maximizing mutual information
      between input patterns and competitive units. One shortcoming of the method is
      that maximizing information does not necessarily produce representations faithful
      to input patterns. Information maximizing primarily focuses on some parts of
      input patterns that are used to distinguish between patterns. Therefore, we
      introduce the cost, which represents average distance between input patterns and
      connection weights. By minimizing the cost, final connection weights reflect
      input patterns well. We applied the method to a political data analysis, a voting
      attitude problem and a Wisconsin cancer problem. Experimental results confirmed
      that, when the cost was introduced, representations faithful to input patterns
      were obtained. In addition, improved generalization performance was obtained
      within a relatively short learning time.

PMID- 16111863
TI  - A regenerating spiking neural network.
AB  - Due to their distributed architecture, artificial neural networks often show a
      graceful performance degradation to the loss of few units or connections. Living
      systems also display an additional source of fault-tolerance obtained through
      distributed processes of self-healing: defective components are actively
      regenerated. In this paper, we present results obtained with a model of
      development for spiking neural networks undergoing sustained levels of cell loss.
      To test their resistance to faults, networks are subjected to random faults
      during development and mutilated several times during operation. Results show
      that, evolved to control simulated Khepera robots in a simple navigation task,
      plastic and non-plastic networks develop fault-tolerant structures which can
      recover normal operation to various degrees.

PMID- 16111865
TI  - Efficient information theoretic strategies for classifier combination, feature
      extraction and performance evaluation in improving false positives and false
      negatives for spam e-mail filtering.
AB  - Spam emails are considered as a serious privacy-related violation, besides being
      a costly, unsolicited communication. Various spam filtering techniques have been
      so far proposed, mainly based on Naive Bayesian algorithms. Other Machine
      Learning algorithms like Boosting trees, or Support Vector Machines (SVM) have
      already been used with success. However, the number of False Positives (FP) and
      False Negatives (FN) resulting through applying various spam e-mail filters still
      remains too high and the problem of spam e-mail categorization cannot be solved
      completely from a practical viewpoint. In this paper, we propose a novel approach
      for spam e-mail filtering based on efficient information theoretic techniques for
      integrating classifiers, for extracting improved features and for properly
      evaluating categorization accuracy in terms of FP and FN. The goal of the
      presented methodology is to empirically but explicitly minimize these FP and FN
      numbers by combining high-performance FP filters with high-performance FN filters
      emerging from a previous work of the authors [Zorkadis, V., Panayotou, M., &
      Karras, D. A. (2005). Improved spam e-mail filtering based on committee machines
      and information theoretic feature extraction. Proceedings of the International
      Joint Conference on Neural Networks, July 31-August 4, 2005, Montreal, Canada].
      To this end, Random Committee-based filters along with ADTree-based ones are
      efficiently combined through information theory, respectively. The experiments
      conducted are of the most extensive ones so far in the literature, exploiting
      widely accepted benchmarking e-mail data sets and comparing the proposed
      methodology with the Naive Bayes spam filter as well as with the Boosting tree
      methodology, the classification via regression and other machine learning models.
      It is illustrated by means of novel information theoretic measures of FP & FN
      filtering performance that the proposed approach is very favorably compared to
      the other rival methods. Finally, it is found that the proposed information
      theoretic Boolean features present a remarkably high spam categorization
      performance.

PMID- 16111866
TI  - Handling missing values in support vector machine classifiers.
AB  - This paper discusses the task of learning a classifier from observed data
      containing missing values amongst the inputs which are missing completely at
      random. A non-parametric perspective is adopted by defining a modified risk
      taking into account the uncertainty of the predicted outputs when missing values
      are involved. It is shown that this approach generalizes the approach of mean
      imputation in the linear case and the resulting kernel machine reduces to the
      standard Support Vector Machine (SVM) when no input values are missing.
      Furthermore, the method is extended to the multivariate case of fitting additive
      models using componentwise kernel machines, and an efficient implementation is
      based on the Least Squares Support Vector Machine (LS-SVM) classifier
      formulation.

PMID- 16111867
TI  - Sphingosine 1-phosphate receptors mediate stimulatory and inhibitory signalings
      for expression of adhesion molecules in endothelial cells.
AB  - Sphingosine 1-phosphate (S1P) stimulates expression of vascular cell adhesion
      molecule-1 and intercellular adhesion molecule-1 in human umbilical vein
      endothelial cells. S1P-induced actions were associated with nuclear factor kappa
      B activation and inhibited by pertussis toxin as well as by antisense
      oligonucleotides specific to S1P receptors, especially, S1P(3). S1P also
      stimulated endothelial nitric oxide synthase (eNOS) and its activation was
      markedly inhibited by the antisense oligonucleotide for the S1P(1) receptor
      rather than that for the S1P(3) receptor. The dose-response curve of S1P to
      stimulate adhesion molecule expression was shifted to the left in the presence of
      the phosphatidylinositol 3-kinase inhibitor wortmannin and the NOS inhibitor
      Nomega-nitro-l-arginine methyl ester. NO donor S-nitroso-N-acetylpenicillamine
      inhibited S1P-induced adhesion molecule expression. Moreover, tumor necrosis
      factor-alpha-induced adhesion molecule expression was markedly inhibited by S1P
      in a manner sensitive to inhibitors for PI3-K and NOS. These results suggest that
      S1P receptors are coupled to both stimulatory and inhibitory pathways for
      adhesion molecule expression. The stimulatory pathway involves nuclear factor
      kappa-B and inhibitory one does phosphatidylinositol 3-kinase and NOS.

PMID- 16111868
TI  - Integrins in metastatic adenoid cystic carcinoma.
AB  - Adenoid cystic carcinoma exhibits a diverse clinical behaviour from very
      localised invasion to widespread metastatases. Recently two adenoid cystic
      carcinoma cells lines have been isolated and cultured which distinctly show
      either a low metastatic tendency (Acc-2) or a highly metastatic behaviour (Acc
      M). It was hypothesised that these two types of behaviour may at least in part be
      explained by the different integrin profile on the cells' surface membrane. The
      integrins represent the largest known family of cell adhesion molecules and a
      number of tumour cell processes have been shown to be dependant on their integrin
      expression. Adenoid cystic carcinoma cells of both types were obtained and
      successfully cultured. These were then subjected to integrin analysis by a number
      of monoclonal antibodies to alpha(1), alpha(2), alpha(3), alpha(v), alpha(6),
      beta(1), alpha(v)beta6, alpha(v)beta4 using a fluorescence activated cell sorter.
      Although there was an apparent difference of integrin expression in the Acc-M
      group as compared to the Acc-2 group, this was not statistically significant. It
      is still possible though, that this might account for the differences in
      behaviour of the two cell lines, and the relationship between integrins, and
      invasion and metastases in other tumours is discussed. The pattern of integrin
      expression in Acc may be prognostically significant and useful for treatment
      planning in the future.

PMID- 16111869
TI  - Microbubble-enhanced ultrasound for gene transfer into living skin equivalents.
AB  - BACKGROUND: Gene transfer to skin is an attractive therapeutic approach because
      of the accessibility of the skin and the high rate of cure for many cutaneous
      diseases. However, safety concerns over viral vectors and the low efficiency of
      most non-viral gene transfer techniques have encumbered their clinical
      application for gene transfer. By contrast, efficient gene transfers into various
      cell types using microbubble-enhanced ultrasound has been reported. OBJECTIVES:
      The purpose of this study was to investigate whether ultrasound with microbubble
      enhancement allowed effective transfer of foreign genes into living skin
      equivalents (LSEs). METHODS: Microbubbles and plasmid DNA encoding green
      fluorescent protein (GFP) were added to the dermal-epidermal junctions of LSEs,
      which were then exposed to ultrasound. The LSEs were harvested at different time
      points to investigate transgene expression using confocal laser microscopy.
      Transfected LSEs were also transplanted onto nude mice, and the in vivo transgene
      expression was observed. RESULTS: From days 2 to 7 after transfection, most GFP
      positive cells continued to migrate upward from the basal layer, while other GFP
      positive cells lagged behind or remained in the basal layer on days 5 and 7.
      Transfection resulted in 20-30% GFP-positive cells. Multiple transfections
      further increased the percentage of transfected cells and resulted in multi-layer
      transgene expression. Grafts from the transfected LSEs survived on nude mice and
      continued to express GFP up to 2 weeks post-transplantation. CONCLUSION: Gene
      transfer into LSE using ultrasound with microbubble enhancement is an effective
      alternative to viral and non-viral methods.

PMID- 16111870
TI  - Reorganization of lipid nanocapsules at air-water interface. I. Kinetics of
      surface film formation.
AB  - The size, the electrical properties and the behaviour at air-water interface of
      lipid nanocapsules (LNC) with various compositions were investigated. Two
      populations of LNC are presented in the suspension after the preparation: with
      (LNC II) and without (LNC I) phospholipid molecules. After the spreading at air
      water interface, a rapid disaggregation of LNC I, located in the vicinity of
      interface, occurs leading to formation of surface film. The phospholipid
      molecules stabilize the structure of nanocapsules and LNC II are more stable at
      the interface in comparison with LNC I. The formation of a surface film was
      followed after by measuring the evolution of the surface pressure, relative
      surface area change and surface potential. A kinetic approach describing the
      various processes during the surface film formation was proposed. The
      corresponding kinetic constants were estimated.

PMID- 16111871
TI  - Absorption properties and P-glycoprotein activity of modified Caco-2 cell lines.
AB  - Caco-2 cell line is extensively used as an in vitro model in studying small
      intestinal absorption but it lacks proper expression of efflux pumps and
      cytochrome P450 enzymes that are involved in absorption and first pass metabolism
      of drugs. We created two novel Caco-2 cell lines expressing orphan nuclear
      receptors pregnane X receptor and constitutive androstane receptor that regulate
      many genes involved in xenobiotic metabolism. We conducted a systematic study on
      expression of some metabolic genes, P-glycoprotein activity and absorption
      properties of several drugs with these new cell lines and previously described
      modified Caco-2 cell lines (MDR1 transfection, vincristine treatment and
      1alpha,25-dihydroxyvitamin D3 treatment). A short culture time medium was also
      included in the study. Most modified cell lines formed tight differentiated
      monolayers. MDR1, CYP2C9 and CYP3A4 genes were upregulated in some cell lines.
      Elevated P-glycoprotein activities were observed by calcein-AM uptake experiments
      but this did not affect significantly the permeability of selected P-glycoprotein
      substrates. Some cell lines had similar passive and active permeability
      properties to Caco/WT cells while in few cell lines these were altered. Passive
      transcellular permeability was modestly elevated in all modified cell lines. In
      addition, several compounds showed pH-dependent permeability properties.

PMID- 16111873
TI  - Kinetics of the inhibition of calcium/calmodulin-dependent protein kinase II by
      pea protein-derived peptides.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) catalyzes the
      phosphorylation of various cellular proteins and excessive activities have been
      implicated in the pathogenesis of various chronic diseases. We hypothesized that
      positively charged peptides can be produced through enzymatic hydrolysis of pea
      proteins; such peptides could then bind to negatively charged calmodulin (CaM) at
      a physiological pH level and inhibit CaMKII activity. Pea protein isolate was
      hydrolyzed with an alkaline protease (alcalase) and filtered through a 1000-mol
      wt cutoff membrane. The permeate, which contained low-molecular weight peptides,
      was used to isolate cationic peptides on an SP-Sepharose column by ion exchange
      chromatography. Separation of the permeate on the SP-Sepharose column yielded two
      fractions with net positive charges that were subsequently used for enzyme
      inhibition studies. Fraction I eluted earlier from the column and contained lower
      contents of lysine and arginine than Fraction II, which eluted later. Results
      show that both peptide fractions inhibited CaMKII activity mostly in a
      competitive manner, although kinetic data suggested that inhibition by Fraction
      II may be of the mixed type. Kinetic analysis (K(m) and K(i)) showed that
      affinity of peptides in Fraction II for CaM was more than that in Fraction I,
      which was directly correlated with the higher inhibitory properties of Fraction
      II against CaMKII. The results suggest that it may be possible to use pea protein
      derived cationic peptides to modulate CaMKII activities.

PMID- 16111872
TI  - trans-10,cis-12 conjugated linoleic acid prevents adiposity but not insulin
      resistance induced by an atherogenic diet in hamsters.
AB  - While conjugated linoleic acid (CLA) has received a great deal of attention as a
      supplement that can favourably modify body composition, its potential impact on
      insulin sensitivity has not received equal attention. The aim of the present work
      was to analyse the effects of trans-10,cis-12 CLA isomer on insulin sensitivity
      in hamsters fed an atherogenic diet. Hamsters were divided into three groups: one
      group was fed a chow diet (control) and the other two a semipurified atherogenic
      diet supplemented with 0.5% linoleic acid (LA) or trans-10,cis-12 CLA,
      respectively. Serum glucose, FFAs, insulin, leptin and adiponectin were measured
      using commercial kits. HOMA-IR was calculated using the formula of Matthews et
      al. PPARgamma mRNA was assessed in epididymal adipose tissue by reverse
      transcription-polymerase chain reaction (RT-PCR). After 6 weeks, atherogenic
      feeding produced an increase in body fat accumulation as compared with control
      feeding. The addition of trans-10,cis-12 CLA to the atherogenic diet avoided this
      feature. Atherogenic feeding also led to significantly higher serum
      concentrations of glucose, insulin, FFAs, as well as greater HOMA-IR values.
      trans-10,cis-12 CLA did not prevent these effects. No significant differences
      were found among experimental groups in serum leptin and adiponectin
      concentrations, nor in PPARgamma expression. In summary, although the addition of
      trans-10,cis-12 CLA to an atherogenic diet reduces fat accumulation, it does not
      improve the impairment of insulin action associated with this feeding. The
      maintenance of insulin resistance in hamsters fed the atherogenic CLA-enriched
      diet is probably due to the high serum FFA concentration observed in these
      animals.

PMID- 16111874
TI  - Wild blueberry (Vaccinium angustifolium) consumption affects the composition and
      structure of glycosaminoglycans in Sprague-Dawley rat aorta.
AB  - It has been documented that increased intake of polyphenols may provide
      protection against coronary heart disease and stroke. Blueberries (Vaccinium
      angustifolium) are one of the richest sources of antioxidants among fruits and
      vegetables. Phenolic compounds from berry extracts inhibit human low density
      lipoprotein and liposome oxidation. Glycosaminoglycans (GAGs) and proteoglycans
      (PGs) are structural components of aortas with great structural diversity. Their
      interaction with compounds such as enzymes, cytokines, growth factors, proteins
      and lipoproteins and their subsequent role in degenerative diseases has been
      documented. We investigated the effects of a diet rich in blueberries on the
      content and structure of GAGs. Sprague-Dawley rats were fed either a control (C)
      or a blueberry (B) diet for 13 weeks. Aortic tissue GAGs were isolated with
      papain digestion, alkaline borohydride treatment and anion-exchange
      chromatography. Cellulose acetate electrophoresis and treatment of the fractions
      with specific lyases revealed the presence of three GAG populations, i.e.
      hyaluronan (HA), heparan sulfate (HS) and galactosaminoglycans (GalAGs).
      Disaccharide composition was determined by high-performance capillary
      electrophoresis following enzymatic degradation. A 13% higher amount of total
      GAGs in aortas of B-fed rats was attributed to a higher content of GalAGs (67%).
      Determination of the sulfated disaccharides showed an overall lower concentration
      of oversulfated disaccharides in both HS and GalAG populations in the aortas of
      the B group. Our results demonstrate for the first time that a diet rich in
      blueberries results in structural alterations in rat aortic tissue GAGs. These
      changes may affect cellular signal transduction pathways and could have major
      consequences for the biological function of GAG molecules within the vascular
      environment.

PMID- 16111875
TI  - Inhibition of matrix metalloproteinase activity in DU145 human prostate cancer
      cells by flavonoids from lowbush blueberry (Vaccinium angustifolium): possible
      roles for protein kinase C and mitogen-activated protein-kinase-mediated events.
AB  - Regulation of the matrix metalloproteinases (MMPs) is crucial to regulate
      extracellular matrix (ECM) proteolysis which is important in metastasis. This
      study investigated the mechanism(s) by which three flavonoid-enriched fractions
      from lowbush blueberry (Vaccinium angustifolium) down-regulate MMP activity in
      DU145 human prostate cancer cells. Metalloproteinase activity was evaluated from
      cells exposed to "crude," anthocyanin-enriched (AN) and proanthocyanidin-enriched
      (PAC) fractions. Differential down-regulation of MMPs was observed. The activity
      of the endogenous tissue inhibitors of metalloproteinases (TIMPs) from these
      cells was also evaluated. Increases in TIMP-1 and TIMP-2 activity were observed
      in response to these fractions. The possible involvement of protein kinase C
      (PKC) and mitogen-activated protein (MAP) kinase pathways in the flavonoid
      mediated decreases in MMP activity was observed. These findings indicate that
      blueberry flavonoids may use multiple mechanisms in down-regulating MMP activity
      in these cells.

PMID- 16111876
TI  - Genistin inhibits UV light-induced plasmid DNA damage and cell growth in human
      melanoma cells.
AB  - In recent years, genistein has received considerable attention because
      epidemiologic studies showed that consumption of soybean-containing diets was
      associated with a lower incidence of certain human cancers in Asian populations.
      In vitro studies further showed that such chemopreventive and antineoplastic
      effects were associated with the antioxidant activity of genistein and inhibitor
      activities on cell proliferation and angiogenesis. Genistein was shown to arrest
      the growth of malignant melanoma in vitro and to inhibit ultraviolet (UV) light
      induced oxidative DNA damage. Recently, it has been demonstrated that genistin,
      as other flavonoid glycosides, is partly absorbed without previous cleavage and
      does not have to be hydrolyzed to be biologically active. Therefore, not only
      isoflavone aglycons, but also glycosides can be of physiological relevance. In
      the present study, we evaluated in cell-free systems the effect of genistin and
      daidzin on pBR322 DNA cleavage induced by hydroxyl radicals, generated from UV
      photolysis of hydrogen peroxide, and their superoxide anion scavenging capacity.
      In addition, we investigated the growth inhibitory activity of these isoflavones
      against human melanoma cell line (M14). Under our experimental conditions,
      genistin and daidzin showed a protective effect on DNA damage and exhibited a
      superoxide dismutase-like effect, but only genistin was able to reduce
      significantly the vitality of M14 cells, confirming the importance of the 5,7
      dihydroxy structure in the A ring. These results suggest that also genistin, due
      to its antioxidant and anticarcinogenic properties, contributes to the overall
      biological activity of soy and could have promising applications in the field of
      dermatology.

PMID- 16111877
TI  - Novel mechanisms of natural antioxidant compounds in biological systems:
      involvement of glutathione and glutathione-related enzymes.
AB  - Polyphenols are wide variety of compounds that occur in fruits and vegetables,
      wine, tea, extra virgin olive oil, chocolate and other cocoa products. Several
      polyphenols have been demonstrated to have clear antioxidant properties in vitro,
      and many of their biological actions have been attributed to their intrinsic
      reducing capabilities. However, this concept appears now to be a simplistic way
      to conceive their activity. Evidence is indeed accumulating that polyphenols
      might exert several other specific biological effects that are as yet poorly
      understood. In this article we review the most recent data on the subject and
      describe the additional functions that polyphenols can have in biological
      systems, focusing on their effects on glutathione and its related enzymes.
      Experimental data indicate that polyhenols may offer an indirect protection by
      activating endogenous defense systems. Several lines of evidence suggest a tight
      connection between exogenous and endogenous antioxidants that appear to act in a
      coordinated fashion. It is reasonable to hypothesize that this is achieved, at
      least in part, through antioxidant responsive elements (AREs) present in the
      promoter regions of many of the genes inducible by oxidative and chemical stress.
      The latest studies strongly suggest that dietary polyphenols can stimulate
      antioxidant transcription and detoxification defense systems through ARE.

PMID- 16111879
TI  - Decreased TGF-beta1 and IGF-1 protein expression in rat embryo skull bone in
      folic acid-restricted diet.
AB  - Folic acid deficiency during conception up to the end of the third month of
      gestation is believed to play the most important factor in neural tube defects
      (NTDs). However, the exact molecular mechanism remains to be elucidated. It has
      been suggested that transforming growth factor-beta (TGF-beta1) and insulin-like
      growth factor-1 (IGF-1) play a critical role in supporting bone formation.
      Therefore, folic acid deficiency may contribute to NTD occurrence via decreased
      TGF-beta1 and IGF-1 expression. This study aimed to determine the correlation
      between folic acid deficiency and the expression of TGF-beta1 and IGF-1 in rat
      skull bone. Thirty female Sprague-Dawley rats were divided into three groups.
      Purified diet containing 5 (restricted), 15 (low) and 30 microg (normal) of folic
      acid was given to the first, second and third groups, respectively. At 16 weeks
      of a given diet, blood samples were taken to examine folic acid (folate
      immunoassay method), TGF-beta1 and IGF-1 (enzyme-linked immunosorbent assay
      method) levels. After forced mating, on the 18th-19th day of gestation (E18-19),
      the pregnant rats were subjected to hysterectomy. The skull bone samples of E18
      19 rats were taken to examine the TGF-beta1 and IGF-1 protein expression by
      immunohistochemistry. The folic acid-restricted diet (5 microg) resulted in
      decreased serum TGF-beta1 and IGF-1 levels. Furthermore, protein expression of
      TGF-beta1 and IGF-1 in E18-19 rat skull bones was also significantly lower in the
      folic acid-restricted diet than in the normal diet. Folic acid deficiency could
      result in reduction of TGF-beta1 and IGF-1 protein levels and might contribute to
      formation of defects in the skull bone as observed in mengingocele patients.

PMID- 16111878
TI  - Protective effects of resveratrol against oxidative/nitrative modifications of
      plasma proteins and lipids exposed to peroxynitrite.
AB  - The protective effects of resveratrol (3, 4', 5-trihydroxystilbene; present
      naturally in different plants) against the oxidative/nitrative damage of human
      plasma proteins induced by peroxynitrite (ONOO-) were studied and compared with
      those of deferoxamine (DFO; a natural siderophore isolated from Streptomyces
      pilosus), which is a typical and well-known antioxidant. We also studied the
      effect of ONOO- on plasma lipid peroxidation and the role of tested antioxidants
      in this process. ONOO- at the used concentrations (0.01-1 mM) showed toxicity to
      human plasma components. Exposure of plasma to ONOO- (0.1 mM) resulted in an
      increase of the level of carbonyl groups and nitrotyrosine residues in plasma
      proteins (approximately 4-fold and 76-fold, respectively) and in a distinct
      augmentation of lipid peroxidation (approximately 2-fold). In the presence of 0.1
      mM resveratrol, a distinct decrease of carbonyl group formation and tyrosine
      nitration in plasma proteins caused by 0.1-mM ONOO- was observed (by
      approximately 70% and 65%, respectively). Addition of 0.1-mM DFO to plasma also
      distinctly reduced the level of carbonyl groups and nitrotyrosines caused by 0.1
      mM ONOO- (by approximately 50% and 60%, respectively). Moreover, these
      antioxidants also inhibited plasma lipid peroxidation induced by ONOO- (0.1 mM).
      The obtained results indicate that in vitro resveratrol, like well-known
      antioxidant DFO, has inhibitory effects on ONOO- -mediated oxidation of proteins
      and lipids in human plasma.

PMID- 16111880
TI  - The role of initial monitoring of routine biochemical nutritional markers in
      critically ill children.
AB  - AIMS: The objectives of this study were to determine whether abnormal values of
      routine laboratory parameters at admission predict outcome and changes in
      anthropometric parameters in critically ill children during intensive care unit
      (ICU) stay and to discuss the clinical implications of abnormalities. STUDY
      DESIGN: This is a prospective descriptive study in a tertiary multidisciplinary
      pediatric ICU. Serum urea, albumin, triglycerides and magnesium were measured in
      samples obtained from 105 children (age, 7 days-16 years) within the first 24 h
      after their admission. The prevalences of abnormalities in these parameters as
      well as their possible association with outcome (length of stay, days on
      mechanical ventilation) and changes in nutritional status (changes in S.D. scores
      for weight, mid upper arm circumference and calf circumference) between admission
      and discharge were assessed. RESULTS: Prevalences of hypomagnesemia,
      hypertriglyceridemia, uremia and hypoalbuminemia were 20%, 25%, 30% and 52%,
      respectively, with no significant associations between the different disorders.
      Except for uremia, no significant association was found between abnormalities in
      biochemical parameters and changes in S.D. scores of anthropometric measurements.
      Children with uremia showed larger declines in S.D. scores for weight and arm
      circumference between admission and discharge than children without uremia did.
      Children with hypertriglyceridemia had longer ventilator dependence (P<.01) and
      length of stay (P<.001) than children with normal triglyceride levels upon
      admission had. CONCLUSIONS: Abnormalities in routine nutritional laboratory
      parameters were frequently noted in critically ill children at admission.
      Detection of abnormalities was not predictive of changes in anthropometric
      parameters during ICU admission but can be important in individualizing
      nutritional support.

PMID- 16111882
TI  - Geoenvironmental behavior of foundry sand amended mixtures for highway subbases.
AB  - The high cost of landfilling and the potential uses of waste foundry sands have
      prompted research into their beneficial reuse. Roadways have a high potential for
      large volume usage of the foundry sands. A laboratory testing program was
      conducted on soil-foundry sand mixtures amended with cement and lime to assess
      their applicability as highway subbase materials. The mixtures were compacted in
      the laboratory at a variety of moisture contents and compactive efforts and
      subjected to unconfined compression, California bearing ratio, and hydraulic
      conductivity tests. The environmental suitability of the prepared mixtures was
      evaluated by analyzing the effluent collected during hydraulic conductivity
      tests. Finally, required subbase thicknesses were calculated using the laboratory
      based strength parameters. The results of the study show that the strength of a
      mixture is highly dependent on the curing period, compactive energy, lime or
      cement presence, and water content at compaction. The resistance of foundry sand
      based specimens to winter conditions is generally better than that of a typical
      subbase reference material. Laboratory leaching tests indicated that if these
      mixtures later come in contact with water that has been discharged directly to
      the environment (e.g., drainage through asphalt pavement), the quality of water
      will not be affected.

PMID- 16111881
TI  - The citrus flavonoid naringenin stimulates DNA repair in prostate cancer cells.
AB  - As part of a systematic study of the effects of phytochemicals beyond
      antioxidation on cancer prevention, we investigated whether naringenin (NR), a
      citrus flavonoid, stimulates DNA repair following oxidative damage in LNCaP human
      prostate cancer cells. The 8-hydroxydeoxyguanosine (8-OH-dG) to deoxyguanosine
      (dG) ratio was measured after cells were treated with 200 micromol/L of ferrous
      sulfate in serum-free medium followed by NR exposure for 24 h in growth medium.
      The results demonstrated that exposure to 10-80 micromol/L of NR led to a
      significant decrease in the ratio of 8-OH-dG to 10(6) dG. Because cells were
      treated with NR after ferrous sulfate was removed, we conclude that we
      demonstrated an effect on DNA repair beyond antioxidation. In support of this
      conclusion, we determined the induction of mRNA expression over time after
      oxidative stress followed by NR administration of three major enzymes in the DNA
      base excision repair (BER) pathway: 8-oxoguanine-DNA glycosylase 1 (hOGG1),
      apurinic/apyrimidinic endonuclease and DNA polymerase beta (DNA poly beta). hOGG1
      and DNA poly beta mRNA expression in cells after 24-h exposure to NR was
      increased significantly compared with control cells without NR. The intracellular
      concentration of NR after exposure to 80 micromol/L was 3 pmol/mg protein, which
      is physiologically achievable in tissues. In conclusion, the cancer-preventive
      effects of citrus fruits demonstrated in epidemiological studies may be due in
      part to stimulation of DNA repair by NR, which by stimulating BER processes may
      prevent mutagenic changes in prostate cancer cells.

PMID- 16111883
TI  - Antioxidant intervention as a route to cancer prevention.
AB  - The notion of cancer prevention through antioxidant intervention arises from the
      fact that fruits and vegetables contain antioxidants and are linked to low cancer
      rates in those who consume them. Protection against DNA damage by plant food
      products can be demonstrated in vitro. However, particular care is needed when
      measuring the damage, since oxidation readily occurs during sample preparation,
      creating a serious artefact. In the case of DNA oxidation, estimates of
      background levels in human cells range over 3 orders of magnitude, depending on
      the method used. Using validated, reliable biomarker assays for DNA oxidation, it
      is possible to demonstrate a decrease in oxidative damage after supplementation
      with isolated antioxidants or whole plant foods in humans. In contrast, in
      several large-scale interventions with disease or death as the endpoint,
      supplementation with beta-carotene resulted in no effect or an increase in cancer
      incidence. It is certainly true that we do not yet fully understand the role of
      phytochemicals as antioxidants, or as modulators of other processes related to
      carcinogenesis and its prevention.

PMID- 16111884
TI  - Vitamin D receptor (VDR) ablation alters carcinogen-induced tumorigenesis in
      mammary gland, epidermis and lymphoid tissues.
AB  - The Vitamin D receptor (VDR) and its ligand, 1,25(OH)(2)D(3), regulate cell
      proliferation, differentiation and apoptosis in vitro, yet the physiological
      significance of this regulation is unclear. In these studies, we used VDR
      knockout (VDRKO) mice to examine the impact of VDR on chemical carcinogen-induced
      tumorigenesis in vivo. Wild type (WT) and VDRKO littermates were fed a high
      calcium diet to prevent disturbances in calcium homeostasis and were gavaged with
      dimethylbenzanthracence (DMBA) using a protocol designed to induce mammary
      tumors. Compared to WT littermates, VDRKO mice exhibited an increased incidence
      of mammary gland hyperplasia and a higher percentage of hormone independent
      tumors with squamous differentiation. VDR ablation also significantly enhanced
      tumor development in epidermis and lymphoid tissues, but did not affect tumor
      development in ovary, uterus, lung or liver. These data indicate that VDR
      ablation alters susceptibility to DMBA-induced carcinogenesis in a tissue
      specific fashion, and provide support that optimal VDR signaling may act to
      suppress tumorigenesis.

PMID- 16111885
TI  - Mechanisms for the selective action of Vitamin D analogs.
AB  - The non-classical effects of 1,25(OH)(2)D(3) create possible therapeutic
      applications for immune modulation (e.g. auto-immune diseases and graft
      rejection), inhibition of cell proliferation (e.g. psoriasis, cancer) and
      induction of cell differentiation (e.g. cancer). The major drawback related to
      the use of 1,25(OH)(2)D(3) is its calcemic effect, which prevents the application
      of pharmacological concentrations. Several analogs are now available that show
      modest to good selectivity with regard to specific effects (e.g. anticancer or
      immune effects or bone anabolism versus hypercalcemia) when tested in appropriate
      in vivo models. The molecular basis for this selectivity is only partially
      understood and probably a variable mixture of mechanisms.

PMID- 16111886
TI  - Screening of active compounds as neuromedin U2 receptor agonist from natural
      products.
AB  - Reporter cell lines are often used for high-throughput screening of natural
      product libraries or chemical libraries to identify new receptor ligands.
      Screening of neuromedin U2 receptor (NMU2R) ligands may be very useful to treat
      obesity for the reason that centrally administered neuromedin U affects feeding
      behavior, energy expenditure, and pituitary. Here, we have developed a stable
      cell line of neuromedin U2 receptor (NMU2R) to screen for its agonist. The
      experimental results demonstrate that icariin, isolated from Herba epimedii, was
      a strong agonist for NMU2R, which could selectively activate NMU2R, but not M1R,
      MC4R, and negative cell lines.

PMID- 16111887
TI  - New dual inhibitors of EGFR and HER2 protein tyrosine kinases.
AB  - A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1
      f][1,2,4]triazine nucleus is described. A general route toward their synthesis,
      which enables functionalization at multiple sites, has been developed. Biological
      evaluation in enzymatic and cell-based assays has identified a series of C-6
      carbamates with potent biochemical and cellular activities.

PMID- 16111888
TI  - Evaluation of the benzothiazole aggregation inhibitors riluzole and PGL-135 as
      therapeutics for Huntington's disease.
AB  - Huntington's disease (HD) is an inherited progressive neurological disorder for
      which there is no effective therapy. It is caused by a CAG/polyglutamine repeat
      expansion that leads to abnormal protein aggregation and deposition in the brain.
      Several compounds have been shown to disrupt the aggregation process in vitro,
      including a number of benzothiazoles. To further explore the therapeutic
      potential of the benzothiazole aggregation inhibitors, we assessed PGL-135 and
      riluzole in hippocampal slice cultures derived from the R6/2 mouse, confirming
      their ability to inhibit aggregation with an EC50 of 40 microM in this system.
      Preliminary pharmacological work showed that PGL-135 was metabolically unstable,
      and therefore, we conducted a preclinical trial in the R6/2 mouse with riluzole.
      At the maximum tolerated dose, we achieved steady-state riluzole levels of 100
      microM in brain. However, this was insufficient to inhibit aggregation in vivo
      and we found no improvement in the disease phenotype.

PMID- 16111889
TI  - Absorption and emission spectroscopic characterisation of combined wildtype LOV1
      LOV2 domain of phot from Chlamydomonas reinhardtii.
AB  - An absorption and emission spectroscopic characterisation of the combined wild
      type LOV1-LOV2 domain string (abbreviated LOV1/2) of phot from the green alga
      Chlamydomonas reinhardtii is carried out at pH 8. A LOV1/2-MBP fusion protein
      (MBP=maltose binding protein) and LOV1/2 with a His-tag at the C-terminus (LOV1/2
      His) expressed in an Escherichia coli strain are investigated. Blue-light photo
      excitation generates a non-fluorescent intermediate photoproduct (flavin-C(4a)
      cysteinyl adduct with absorption peak at 390 nm). The photo-cycle dynamics is
      studied by dark-state absorption and fluorescence measurement, by following the
      temporal absorption and emission changes under blue and violet light exposure,
      and by measuring the temporal absorption and fluorescence recovery after light
      exposure. The fluorescence quantum yield, phi(F), of the dark adapted samples is
      phi(F)(LOV1/2-His) approximately 0.15 and phi(F)(LOV1/2-MBP) approximately 0.17.
      A bi-exponential absorption recovery after light exposure with a fast (in the
      several 10-s range) and a slow component (in the near 10-min range) are resolved.
      The quantum yield of photo-adduct formation, phi(Ad), is extracted from
      excitation intensity dependent absorption measurements. It decreases somewhat
      with rising excitation intensity. The behaviour of the combined wildtype LOV1
      LOV2 double domains is compared with the behaviour of the separate LOV1 and LOV2
      domains.

PMID- 16111890
TI  - Circadian rhythms of resistance to UV-C and UV-B radiation in Euglena as related
      to "escape from light" and "resistance to light".
AB  - Radiation-induced stress, either from visible or UV light, is strongest at
      midday. We found that, in the absence of stress or time cues, Euglena gracilis Z
      was the most resistant to UV-C and UV-B at subjective midday, whether judged from
      immediate or reproductive survival. The circadian UV-resistance rhythms were free
      running in stationary cultures under 1-h light/1-h dark cycles or continuous
      darkness, indicating that cell-cycle dependent DNA susceptibility to UV was not
      involved. We moreover examined what was the primary cause of the circadian UV
      resistance, estimated as the immediate cell survival. The half-maximal lethal
      dose (LD(50)) of UV-C at subjective midday (the most resistant phase) was 156
      J/m(2), which is approximately 3-fold that at subjective midnight. The same was
      true for UV-B, except the LD(50) was approximately 13-fold that of UV-C.
      Temperature during UV irradiation had little effect, indicating that survival was
      not mediated via enzymatic reactions. Non-enzymatic antioxidants were added 5 min
      before UV irradiation. Dimethylsulfoxide (a hydroxyl radical scavenger) increased
      survival after UV-B, but had little effect after UV-C; conversely, sodium
      ascorbate increased survival after UV-C, but not after UV-B. These findings
      suggest that circadian rhythms of resistance to UVs involve a common mechanism
      for maximizing non-enzymatic antioxidative capacity at subjective midday, but the
      specific antioxidants differ.

PMID- 16111891
TI  - Investigation of local ACE activity and structural alterations during development
      of L-NAME-induced hypertension.
AB  - Tonic basal release of nitric oxide (NO) by vascular endothelial cells controls
      blood pressure (BP) in the basal state. In the present study, we showed how serum
      and local angiotensin converting enzyme (ACE) alters during development of
      hypertension in chronic nitric oxide synthase blockade, a non-renin-dependent
      model of hypertension. Four experiments were performed in which animals were
      given N(omega)-nitro-L-arginine methyl ester (L-NAME) (50 mg kg(-1)) for 2, 4, 8
      and 12 weeks. The control group rats received tap water. The ACE activity in
      serum, aorta, heart, kidney and lung was analyzed by high performance liquid
      chromatography (HPLC) and the structural change in aorta was investigated by
      measurement of cross-sectional area (CSA). Significant elevation of systolic
      blood pressure developed in chronically NO-blocked rats compared to controls.
      These results indicated that ACE activity in aortae and heart was gradually
      increased during development of hypertension and was more pronounced at higher
      blood pressure. Furthermore, there was a positive correlation between aortic
      cross-sectional area and elevation of blood pressure. These observations
      highlight the importance of the local ACE particularly in organs regulating
      hypertension (aorta and heart) during development of L-NAME-induced hypertension.

PMID- 16111892
TI  - Ocular abnormalities in Large(myd) and Large(vls) mice, spontaneous models for
      muscle, eye, and brain diseases.
AB  - Here we demonstrate previously unreported ocular defects in mice homozygous for a
      new allele of the Large gene, veils, and for Large(myd) mice. Clinically, vitreal
      fibroplasia and retinal vessel tortuosity and fluorescein leakage are observed.
      These vascular defects may be due to the extreme disorganization of the
      astrocytic template on which endothelial cells migrate in the retina. Abnormal
      electroretinograms recorded from Large(vls) or Large(myd) mice are accompanied by
      disorganization of the outer plexiform layer (OPL) with a dramatic reduction in
      the number of synaptic complexes. In both mutants, the internal limiting membrane
      (ILM) is disrupted with ectopic cells in the vitreous. Interestingly, while all
      components of the dystrophin glycoprotein complex are present at reduced levels
      in the OPL, they were absent in the ILM of affected mice. Finally,
      hypoglycosylation of alpha-dystroglycan previously implicated in muscle and brain
      defects is also observed in the retina and may contribute to the ocular
      abnormalities.

PMID- 16111893
TI  - Assessing acetylation of NF-kappaB.
AB  - To achieve its full biological activity, NF-kappaB must undergo a variety of post
      translational modifications, including acetylation. Acetylation plays a prominent
      role in regulating the nuclear action of NF-kappaB. The RelA subunit of NF-kappaB
      forms the major target of acetylation at several different sites. Acetylation of
      discrete lysine residues in RelA modulates distinct functions of NF-kappaB,
      including transcriptional activation, DNA binding, and assembly with its
      inhibitor IkappaBalpha. Here, we describe the experimental methods that have
      allowed the detection and functional analysis of acetylated forms of NF-kappaB.
      Acetylation of NF-kappaB can be studied both in vivo and in vitro. In vivo
      [3H]acetate labeling assays provides a useful, albeit rather insensitive, method
      for initial verification of acetylation of either over-expressed or endogenous
      subunits of NF-kappaB. A second valuable in vivo approach involves the use of
      anti-acetylated lysine antibodies for immunoblotting. However, the success of
      this approach varies with the specific antibody employed and the target protein
      studied. In vitro acetylation assays provide a rapid and sensitive method to
      validate the involvement of candidate histone acetyltransferases and to map the
      sites of acetylation. Anti-RelA antibodies that selectively react with site
      specific acetylated forms of RelA are a singularly powerful tool for the study of
      NF-kappaB acetylation both in vivo and in vitro.

PMID- 16111894
TI  - Biomechanical characteristics of adults walking in shallow water and on land.
AB  - Although water environment has been employed for different physical activities,
      there is little available information regarding the biomechanical characteristics
      of walking in shallow water. In the present study, we investigated the
      kinematics, ground reaction forces (GRF), and electromyographic (EMG) activation
      patterns of eight selected muscles of adults walking in shallow water and on
      land. Ten healthy adults were videotaped while walking at self-selected
      comfortable speeds on land and in water (at the Xiphoid process level). In both
      conditions there was a force plate embedded in the middle of each walkway to
      register the GRF components. Reflective markers were placed over main anatomical
      landmarks and they were digitalized later to obtain stride characteristics and
      joint angle information. In general, walking in water was different to walking on
      land in many aspects and these differences were attributed to the drag force, the
      apparent body weight reduction, and the lower comfortable speed during walking in
      shallow water. The joint range of motions (ROM) were not different, the segment
      ROM, magnitudes of GRF components, impact force, and impulse were different
      between the two conditions. The present results will contribute to a better
      understanding of this activity in the context of training and rehabilitation.

PMID- 16111895
TI  - EMG modulation in anticipation of a possible trip during walking in young and
      older adults.
AB  - This study investigated whether changes in lower limb muscle activity occurred in
      anticipation of a possible perturbation in 11 young (mean age 27 years) and 11
      older (mean age 68 years) adults. Altered muscle activity could affect tripping
      responses and consequently the ecological validity of experimental results of
      studies on tripping. It was hypothesized that anticipatory muscle activity would
      be present immediately after a trip, and decrease after several subsequent
      unperturbed (forewarned) walking trials. Electromyograms of lower limb muscles
      were measured in 3 conditions: during normal walking, during forewarned walking
      immediately after a trip, and during forewarned walking several trials after a
      trip had occurred. Small but statistically significant differences in averaged
      muscle activity over a stride were found among conditions. Young adults showed
      slightly increased activity immediately after tripping (co-contraction) in
      hamstrings, quadriceps and tibialis anterior muscles. This increased activity
      diminished after several unperturbed trials, although it did not return to the
      baseline activity levels during normal walking. In older adults, an increased
      muscle activity among conditions was only discerned in tibialis anterior and
      soleus muscles. This suggested that older adults prefer to avoid contact with the
      obstacle over joint stiffening. Yet, for both age-groups, the increases in muscle
      activity were very small when compared to tripping responses reported in the
      literature. Therefore, anticipatory effects are not expected to jeopardize the
      validity of experiments in which subjects are perturbed more than once.

PMID- 16111896
TI  - Kinematic and EMG characteristics of simple shoulder movements with
      proprioception and visual feedback.
AB  - The objective of this study was to determine if simple, shoulder movements use
      the dual control hypothesis strategy, previously demonstrated with elbow
      movements, and to see if this strategy also applies in the absence of visual
      feedback. Twenty subjects were seated with their right arm abducted to 90 degrees
      and externally rotated in the scapular plane. Subjects internally rotated to a
      target position using a custom shoulder wheel at three different speeds with and
      without visual feedback. Kinematics were collected with a motion analysis system
      and electromyographic (EMG) recordings of the pectoralis major (PECT),
      infraspinatus (INFRA), anterior and posterior (ADELT, PDELT) deltoid muscles were
      used to evaluate muscle activity patterns during movements. Kinematics changed as
      movement speed increased with less accuracy (p<0.01). Greater EMG activity was
      observed in the PECT, PDELT, and INFRA with shorter durations for the ADELT,
      PDELT and INFRA. Movements with only kinesthetic feedback were less accurate
      (p<0.01) and performed faster (p<0.01) than movements with visual feedback. EMG
      activity suggests no major difference in CNS control strategies in movements with
      and without visual feedback. Greater resolution with visual feedback enables the
      implementation of a dual control strategy, allowing greater movement velocity
      while maintaining accuracy.

PMID- 16111897
TI  - Flow-based fiber tracking with diffusion tensor and q-ball data: validation and
      comparison to principal diffusion direction techniques.
AB  - In this study, we evaluate the performance of a flow-based surface evolution
      fiber tracking algorithm by means of a physical anisotropic diffusion phantom
      with known connectivity. We introduce a novel speed function for surface
      evolution that is derived from either diffusion tensor (DT) data, high angular
      resolution diffusion (HARD) data, or a combined DT-HARD hybrid approach. We use
      the model-free q-ball imaging (QBI) approach for HARD reconstruction. The
      anisotropic diffusion phantom allows us to compare and evaluate the performance
      of different fiber tracking approaches in the presence of real imaging artifacts,
      noise, and subvoxel partial volume averaging of fiber directions. The surface
      evolution approach, using the full diffusion tensor as opposed to the principal
      diffusion direction (PDD) only, is compared to PDD-based line propagation fiber
      tracking. Additionally, DT reconstruction is compared to HARD reconstruction for
      fiber tracking, both using surface evolution. We show the potential for surface
      evolution using the full diffusion tensor to map connections in regions of
      subvoxel partial volume averaging of fiber directions, which can be difficult to
      map with PDD-based methods. We then show that the fiber tracking results can be
      improved by using high angular resolution reconstruction of the diffusion
      orientation distribution function in cases where the diffusion tensor model fits
      the data poorly.

PMID- 16111898
TI  - When visual perception causes feeling: enhanced cross-modal processing in
      grapheme-color synesthesia.
AB  - In synesthesia, stimulation of one sensory modality (e.g., hearing) triggers a
      percept in another, non-stimulated sensory modality (e.g., vision). Likewise,
      perception of a form (e.g., a letter) may induce a color percept (i.e., grapheme
      color synesthesia). To date, the neural mechanisms underlying synesthesia remain
      to be elucidated. We disclosed by fMRI, while controlling for surface color
      processing, enhanced activity in the left intraparietal cortex during the
      experience of grapheme-color synesthesia (n = 9). In contrast, the perception of
      surface color per se activated the color centers in the fusiform gyrus
      bilaterally. The data support theoretical accounts that grapheme-color
      synesthesia may originate from enhanced cross-modal binding of form and color. A
      mismatch of surface color and grapheme induced synesthetically felt color
      additionally activated the left dorsolateral prefrontal cortex (DLPFC). This
      suggests that cognitive control processes become active to resolve the perceptual
      conflict resulting from synesthesia.

PMID- 16111899
TI  - Lack of taxonomic differentiation in an apparently widespread freshwater isopod
      morphotype (Phreatoicidea: Mesamphisopidae: Mesamphisopus) from South Africa.
AB  - The unambiguous identification of phreatoicidean isopods occurring in the
      mountainous southwestern region of South Africa is problematic, as the most
      recent key is based on morphological characters showing continuous variation
      among two species: Mesamphisopus abbreviatus and M. depressus. This study uses
      variation at 12 allozyme loci, phylogenetic analyses of 600 bp of a COI
      (cytochrome c oxidase subunit I) mtDNA fragment and morphometric comparisons to
      determine whether 15 populations are conspecific, and, if not, to elucidate their
      evolutionary relationships. Molecular evidence suggested that the most easterly
      population, collected from the Tsitsikamma Forest, was representative of a yet
      undescribed species. Patterns of differentiation and evolutionary relationships
      among the remaining populations were unrelated to geographic proximity or
      drainage system. Patterns of isolation by distance were also absent. An apparent
      disparity among the extent of genetic differentiation was also revealed by the
      two molecular marker sets. Mitochondrial sequence divergences among individuals
      were comparable to currently recognized intraspecific divergences. Surprisingly,
      nuclear markers revealed more extensive differentiation, more characteristic of
      interspecific divergences. This disparity and the mosaic pattern of
      differentiation may be driven by stochastic population crashes and genetic
      bottlenecks (caused by seasonal habitat fluctuations), coupled with genetic
      drift.

PMID- 16111900
TI  - Confrontation of morphological and molecular data: the Praomys group (Rodentia,
      Murinae) as a case of adaptive convergences and morphological stasis.
AB  - Phylogenetic relationships in a group of 21 African rodent species designated as
      the Praomys group (Murinae) were investigated using morphological characters and
      sequence data from the complete mitochondrial cytochrome b gene and nuclear IRBP
      gene fragment (840bp). The molecular results confirm the monophyly of the Praomys
      group, including the species Malacomys verschureni, while the other Malacomys
      species appear very divergent. The basal relationships within the Praomys group
      are poorly resolved, suggesting a rapid radiation at about 7-9 million years ago
      based on genetic divergence rates calibrated from the fossil record.
      Discrepancies between molecular and morphological results probably reflect of
      numerous convergences as well as variations in the rates of morphological
      evolution among lineages. Reconstructions of the ancestral character states
      suggest a savannah origin for the Praomys group, along with some morphological
      traits conserved by stasis in savannah taxa. At the same time, forest taxa seem
      to be characterized by an accelerated morphological evolution, with acquisition
      of convergent adaptive characters.

PMID- 16111901
TI  - Evidence that baroreflex feedback influences long-term incidental visual memory
      in men.
AB  - Sympathetic nervous system (SNS) activity at the time of acquisition is
      associated with human memory. However, rather than SNS activity per se, it may be
      afferent baroreflex feedback that is responsible for this effect. A
      pharmacological design was employed to unload (SNP, sodium nitro-prusside) and
      load (norepinephrine) baroreceptors. In addition to two placebo periods,
      epinephrine and esmolol (a peripherally acting beta1-blocker) served as control
      conditions for altered cardiac perception. During drug infusion blood pressure,
      heart rate, and perception of heartbeat were tested. Twenty-four healthy men were
      participated. The participants viewed emotional slides while their
      electromyographic eye blink responses to random noise bursts were measured
      (affective startle modulation paradigm) to determine potential drug impact on
      emotional processing. Subjects were not informed that memory testing would take
      place after 4 weeks. Drugs did not impact startle, thus indicating unbiased
      emotional processing at the time of acquisition. Norepinephrine had no effect on
      heartbeat perception, but improved (p = .002) recognition memory. SNP (p = .0001)
      increased heartbeat perception but impaired (p = .038) recognition memory.
      Epinephrine, on the other hand, increased heartbeat perception (p = .0001) yet
      did not impair but partially improve memory (effect on high arousing pictures
      only: p = .05). Heartbeat perception in the placebo condition did not correlate
      with recognition memory (p's > .5). We suggest that baroreflex unloading, with
      subsequent feedback activation of the SNS, impairs long-term incidental visual
      recognition memory in humans while baroreflex loading enhances it. Further, we
      propose that these memory effects are neither secondary to cardiac sensations
      that accompany SNS activation nor to altered emotional picture processing at the
      time of acquisition.

PMID- 16111902
TI  - A novel ferroportin mutation in a Canadian family with autosomal dominant
      hemochromatosis.
AB  - We report a new mutation, Asn185Asp, in exon 6 of the ferroportin gene (FPN1) in
      15 members of three successive generations of a Canadian family of Scandinavian
      origin with autosomal dominant hemochromatosis. Hyperferritinemia with low
      transferrin saturation was noted in younger family members, seven of whom were
      aged 20 years or less at the time of diagnosis. In those individuals first
      diagnosed with hemochromatosis in later life, marked hyperferritinemia was
      accompanied by high transferrin saturation. In contrast to the phenotype of high
      ferritin with low saturation first reported for ferroportin disease, this family
      demonstrates a phenotype of iron indices that varies with age.

PMID- 16111903
TI  - Poly(ADP-ribose) polymerase activation by reactive nitrogen species--relevance
      for the pathogenesis of inflammation.
AB  - Oxidative and nitrosative stress triggers DNA strand breakage, which then
      activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP). Nitrogen-derived
      reactive oxidant species capable of involving DNA single strand breakage and PARP
      activation include peroxynitrite (the reaction product of nitric oxide and
      superoxide), but not nitric oxide per se. Activation of PARP may dramatically
      lower the intracellular concentration of its substrate, nicotinamide adenine
      dinucleotide, thus slowing the rate of glycolysis, electron transport, and
      subsequently ATP formation. This process can result in cell dysfunction and cell
      death. Here we review the role of reactive nitrogen species in the process of
      PARP activation, followed by the effect of pharmacological inhibition or genetic
      inactivation of PARP on the course of various forms of inflammation.

PMID- 16111904
TI  - Detection of intracellular lactate with localized diffusion {1H-13C}-spectroscopy
      in rat glioma in vivo.
AB  - The aim of this study was to compare the diffusion characteristic of lactate and
      alanine in a brain tumor model to that of normal brain metabolites known to be
      mainly intracellular such as N-acetylaspartate or creatine. The diffusion of
      (13)C-labeled metabolites was measured in vivo with localized NMR spectroscopy at
      9.4 T (400 MHz) using a previously described localization and editing pulse
      sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). (13)C
      labeled glucose was administered and the apparent diffusion coefficients of the
      glycolytic products, {(1)H-(13)C}-lactate and {(1)H-(13)C}-alanine, were
      determined in rat intracerebral 9L glioma. To obtain insights into {(1)H-(13)C}
      lactate compartmentation (intra- versus extracellular), the pulse sequence used
      very large diffusion weighting (50 ms/microm(2)). Multi-exponential diffusion
      attenuation of the lactate metabolite signals was observed. The persistence of a
      lactate signal at very large diffusion weighting provided direct experimental
      evidence of significant intracellular lactate concentration. To investigate the
      spatial distribution of lactate and other metabolites, (1)H spectroscopic images
      were also acquired. Lactate and choline-containing compounds were consistently
      elevated in tumor tissue, but not in necrotic regions and surrounding normal
      appearing brain. Overall, these findings suggest that lactate is mainly
      associated with tumor tissue and that within the time-frame of these experiments
      at least some of the glycolytic product ([(13)C] lactate) originates from an
      intracellular compartment.

PMID- 16111905
TI  - Visualizing flow vortices inside a single levitated drop.
AB  - The internal flow dynamics in single liquid drops, kept in place through
      levitation by a counterflowing continuous fluid phase in a suitably designed
      glass cell, is investigated by PFG NMR techniques. The positional stability of
      the drops was confirmed from series of one-dimensional profiles and was found to
      be below the spatial resolution of the experiment. Velocity distribution
      functions (propagators) along all three coordinates were obtained and
      demonstrated the long-time stability of the internal dynamics in terms of the
      velocity magnitudes occurring in the systems. Finally, velocity imaging was
      applied to visualize the internal vortex patterns in the drops either as
      projections onto different planes or within thin slices of selected orientations.
      Two different fluid systems were investigated in order to cover the principal
      cases of rigid and mobile interfaces. Different fast velocity imaging techniques
      were employed for monitoring the vastly differing velocity ranges of both cases,
      and the high sensitivity of the internal three-dimensional motion to the cell
      geometry is demonstrated.

PMID- 16111906
TI  - RF probe recovery time reduction with a novel active ringing suppression circuit.
AB  - A simple Q-damper device for active probe recovery time reduction is introduced
      along with a straightforward technique for the circuit's component value
      optimization. The device is inductively coupled to a probe through a coupling
      transformer positioned away from the main coil, which makes the design
      independent of the coil type being used. The Q-damper is a tuned circuit, which
      is resonant at the same frequency as the probe and can be actively interrupted.
      When the circuit is interrupted, it is detuned and, thereby, is uncoupled from
      the probe, which operates normally. Turning the device on leads to re-coupling of
      the circuits and causes splitting of the probe's resonance line, which can be
      observed through its drive port. A resistance of an appropriate value is
      introduced into the Q-damper circuit, resulting in smoothing of the resonance
      splitting into one broad line, representing the coupled system's low-Q state, in
      which the energy stored in the main coil is efficiently dissipated. The circuit's
      component values are optimized by monitoring the shape of this low-Q state. Probe
      recovery time reduction by, approximately, an order of magnitude has been
      obtained with this device. Application of the device during an NQR experiment led
      to an increase in the signal-to-noise ratio by a factor of 4.9.

PMID- 16111907
TI  - Preparing for winter: divergence in the summer-autumn hematological profiles from
      representative species of the squirrel family.
AB  - We examined hematological parameters in four related sciurid species in the late
      summer-autumn to assess the role of habitat, elevation, body size, and behavior
      in shaping these parameters. Red squirrels (Tamiasciurus hudsonicus) and Arctic
      ground squirrels (Spermophilus parryii) were sampled in southwestern Yukon,
      yellow-pine chipmunks (Tamias amoenus) in southern Alberta, and the eastern grey
      squirrel (Sciurus carolinensis) in southern Ontario. We obtained whole blood
      samples from each species and compared glucose levels, red blood cell
      characteristics (hematocrit, red blood cell count, hemoglobin concentration, mean
      corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin
      concentration), and white blood cell counts (neutrophils, lymphocytes, monocytes,
      eosinophils, basophils) across species. We found species differences in glucose
      and red blood cell characteristics that may be a function of activity levels,
      phylogeny, or elevation, but not of body size, body condition, or adaptations to
      a semi-fossorial habitat. We also found species differences in white blood cell
      counts that remain unexplained by any single simple explanation and may be more
      useful for comparison of individuals within a given species than for interspecies
      comparisons.

PMID- 16111908
TI  - Starvation and diet composition affect mRNA levels of the high density
      lipoprotein-beta glucan binding protein in the shrimp Litopenaeus vannamei.
AB  - A high density lipoprotein-beta glucan binding protein (HDL-BGBP) is synthesized
      in the hepatopancreas of the white shrimp Litopenaeus vannamei and secreted to
      the hemolymph. Recently, we reported the HDL-BGBP full length cDNA sequence and
      found that the predicted polypeptide is larger than the mature protein and also,
      that it contains a long 5'- and 3'-UTRs that may be involved in transcript level
      regulation. To test whether starvation and feeding may play a role in regulating
      HDL-BGBP mRNA levels, two different stimuli were evaluated: starvation and
      composition of diets. After 24 h, the steady state HDL-BGBP mRNA levels of
      starved shrimp decreased, suggesting that synthesis of the lipoprotein is less
      required in the absence of food. When shrimp were fed with diets containing
      different concentrations of protein and lipids, changes in HDL-BGBP mRNA levels
      were also detected. Shrimp fed the lower concentration of protein and lipid feed
      accumulated higher levels of HDL-BGBP mRNA. These results indicate that feeding
      influences HDL-BGBP transcript levels in the hepatopancreas.

PMID- 16111909
TI  - Evolution of the transferrin family: conservation of residues associated with
      iron and anion binding.
AB  - The transferrin family spans both vertebrates and invertebrates. It includes
      serum transferrin, ovotransferrin, lactoferrin, melanotransferrin, inhibitor of
      carbonic anhydrase, saxiphilin, the major yolk protein in sea urchins, the
      crayfish protein, pacifastin, and a protein from green algae. Most (but not all)
      contain two domains of around 340 residues, thought to have evolved from an
      ancient duplication event. For serum transferrin, ovotransferrin and lactoferrin
      each of the duplicated lobes binds one atom of Fe (III) and one carbonate anion.
      With a few notable exceptions each iron atom is coordinated to four conserved
      amino acid residues: an aspartic acid, two tyrosines, and a histidine, while
      anion binding is associated with an arginine and a threonine in close proximity.
      These six residues in each lobe were examined for their evolutionary conservation
      in the homologous N- and C-lobes of 82 complete transferrin sequences from 61
      different species. Of the ligands in the N-lobe, the histidine ligand shows the
      most variability in sequence. Also, of note, four of the twelve insect
      transferrins have glutamic acid substituted for aspartic acid in the N-lobe (as
      seen in the bacterial ferric binding proteins). In addition, there is a wide
      spread substitution of lysine for the anion binding arginine in the N-lobe in
      many organisms including all of the fish, the sea squirt and many of the unusual
      family members i.e., saxiphilin and the green alga protein. It is hoped that this
      short analysis will provide the impetus to establish the true function of some of
      the TF family members that clearly lack the ability to bind iron in one or both
      lobes and additionally clarify the evolutionary history of this important family
      of proteins.

PMID- 16111910
TI  - Sonochemical epoxidation of cyclohexene in R-CN/H2O2 system.
AB  - Cyclohexene is efficiently epoxidized by the R-CN/H2O2 system under ultrasonic
      irradiation. Different nitriles can be used to generate in situ the oxidizing
      peroxycarboximidic acids. Reduction of the organic solvent quantities and their
      replacement by water also gives good results.

PMID- 16111911
TI  - Delirium in Parkinson's disease patients. a five-year follow-up study.
AB  - OBJECTIVE: To assess the significance of delirium in parkinsonian patients in a 5
      year follow-up case-control study with three groups of patients: Parkinsonian and
      Delirium (PDG), Parkinsonian (PG) and Control (CG). METHODS: Comparisons of Short
      Test of Mental Status (STMS) and Unified Parkinson's Disease Rating Scale-motor
      section (UPDRS(m)) between groups were performed using analysis of variance with
      repeated measurements. Comparisons of survival functions and Cox regression
      models were used to analyse the time until death. RESULTS: STMS and UPDRS(m) mean
      scores were statistically different between PDG group and the other two groups (p
      < 0.001) and between PDG and PG groups (p < 0.001), respectively. Including all
      groups, PG's patients (HR = 0.29; 95% C.I. = 0.09-0.93) and CG's patients (HR =
      0.13; 95% C.I. = 0.03-0.60) had less hazard to die than PDG's patients; patients
      with a STMS basal score >33 (HR = 0.37; 95% C.I. = 0.13-0.99) had less hazard to
      die than patients with a score < or =33. Finally, including PDG and PG groups,
      patients with basal UPDRS(m) score >17 (HR = 4.88; 95% C.I. = 1.11-21.48) had
      higher hazard to die than patients with a score < or =17. CONCLUSION: For
      patients with Parkinson's, delirium is an increased risk factor for developing
      dementia, to have a more severe motor impairment and to death.

PMID- 16111912
TI  - Staphylococcus aureus: Staphylokinase.
AB  - Staphylokinase is a 136 aa long bacteriophage encoded protein expressed by
      lysogenic strains of Staphylococcus aureus. Present understanding of the role of
      staphylokinase during bacterial infection is based on its interaction with the
      host proteins, alpha-defensins and plasminogen. alpha-Defensins are bactericidal
      peptides originating from human neutrophils. Binding of staphylokinase to alpha
      defensins abolishes their bactericidal properties, which makes staphylokinase a
      vital tool for staphylococcal resistance to host innate immunity. Complex binding
      between staphylokinase and plasminogen results in the formation of active
      plasmin, a broad-spectrum proteolytic enzyme facilitating bacterial penetration
      into the surrounding tissues. We have recently shown high levels of
      staphylokinase expression in clinical isolates of skin and mucosal origin and
      relative low levels in isolates invading internal organs. These findings are
      supported by sepsis studies using isogenic S. aureus strains demonstrating
      increased bacterial load in the absence of staphylokinase production. Our
      observations indicate that staphylokinase favours symbiosis of staphylococci with
      the host that makes it an important colonization factor.

PMID- 16111913
TI  - Normalized mutual information based registration using k-means clustering and
      shading correction.
AB  - In this paper the influence of intensity clustering and shading correction on
      mutual information based image registration is studied. Instead of the generally
      used equidistant re-binning, we use k-means clustering in order to achieve a more
      natural binning of the intensity distribution. Secondly, image inhomogeneities
      occurring notably in MR images can have adverse effects on the registration. We
      use a shading correction method in order to reduce these effects. The method is
      validated on clinical MR, CT and PET images, as well as synthetic MR images. It
      is shown that by employing clustering with inhomogeneity correction the number of
      misregistrations is reduced without loss of accuracy thus increasing robustness
      as compared to the standard non-inhomogeneity corrected and equidistant binning
      based registration.

PMID- 16111914
TI  - Improving on nature: antibiotics that target the ribosome.
AB  - Antibiotic resistance, along with the resolution of antibiotic-ribosomal subunit
      complexes at the atomic level, has provided new insights into modifications of
      clinically relevant antimicrobials that target the ribosome. Modifications to the
      aminoglycoside or negamycin scaffolds have been reported in the past, but few
      derivatives appear to be greatly improved compared to their parent compound.
      Computational and/or traditional screening efforts have yielded novel compounds
      that bind to the decoding site of the small (30S) ribosomal subunit;
      naphthyridones appear to bind only in the presence of poly(U) and tRNA(Phe),
      whereas quinolines bind in a similar manner to aminoglycosides. Streptogramin B
      analogs were designed that have an amide replacement of the labile ester bond.
      The resultant molecules were not substrates for the inactivating lyase, but were
      no longer inhibitors of translation. The synthesis of 16-membered macrolides that
      are modified at the C6 position with peptidyl moieties as well as conjugates of
      chloramphenicol to either nucleotide groups or pyrene have been described, but no
      antibacterial activity has been reported. X-ray crystal structures are now
      available that can be used to improve on natural or synthetic antibiotics that
      bind to either the 30S or the 50S ribosomal subunit.

PMID- 16111915
TI  - Evolutionary and functional genomics of the Archaea.
AB  - In the past two years, archaeal genomics has achieved several breakthroughs. On
      the evolutionary front the most exciting development was the sequencing and
      analysis of the genome of Nanoarchaeum equitans, a tiny parasitic organism that
      has only approximately 540 genes. The genome of Nanoarchaeum shows signs of
      extreme rearrangement including the virtual absence of conserved operons and the
      presence of several split genes. Nanoarchaeum is distantly related to other
      archaea, and it has been proposed to represent a deep archaeal branch that is
      distinct from Euryarchaeota and Crenarchaeota. This would imply that many
      features of its gene repertoire and genome organization might be ancestral.
      However, additional genome analysis has provided a more conservative suggestion -
      that Nanoarchaeum is a highly derived euryarchaeon. Also there have been
      substantial developments in functional genomics, including the discovery of the
      elusive aminoacyl-tRNA synthetase that is involved in both the biosynthesis of
      cysteine and its incorporation into proteins in methanogens, and the first
      experimental validation of the predicted archaeal exosome.

PMID- 16111916
TI  - Anaemia and coronary artery disease severity in patients with heart failure.
AB  - BACKGROUND: Anaemia is common in heart failure (HF) and associated with higher
      mortality. Exacerbation of myocardial ischemia in patients with heart failure,
      coronary disease, and anaemia patients has been suggested as a potential
      mechanism underlying this association. AIMS: The aim of this study was to
      evaluate the hypothesis that greater CAD severity would exacerbate the adverse
      effects of anaemia in HF. METHODS: We examined data on patients with symptomatic
      heart failure (NYHA class > or = II) undergoing coronary angiography between 1995
      and 2003 (n = 4951). Patients with primary valvular or congenital heart disease
      were excluded. Cox proportional hazards modeling was used to evaluate the
      relationship between coronary disease severity (as defined by no. of diseased
      vessels) and hemoglobin concentration. RESULTS AND CONCLUSIONS: In patients with
      symptomatic HF undergoing coronary angiography, we found an interaction between
      hemoglobin and CAD severity (p = 0.003 for interaction). Contrary to our
      hypothesis, the mortality hazard associated with anaemia was greatest in patients
      without CAD and progressively lower with increasing CAD severity. These data
      suggest that anaemia may exert its effect on HF outcomes through mechanisms
      beyond simply the exacerbation of myocardial ischemia.

PMID- 16111917
TI  - Transient biventricular dysfunction following pericardiocentesis.
AB  - We report the case of a 41-year-old woman admitted to the hospital due to cardiac
      tamponade as the first manifestation of a pulmonary neoplasm. The patient
      developed an early biventricular dysfunction and pulmonary edema after removal of
      the pericardial effusion, with complete recovery within ten days. Since transient
      ventricular dysfunction after pericardiocentesis is a very unusual complication,
      we present a review of the different mechanisms suggested in the literature to
      explain the pathophysiology of this rare phenomenon.

PMID- 16111918
TI  - Myocardial biopsy findings and gadolinium enhanced cardiovascular magnetic
      resonance in dilated cardiomyopathy.
AB  - BACKGROUND: In some patients suffering from dilated cardiomyopathy (DCM) magnetic
      resonance imaging (MRI) shows late gadolinium enhancement with variable
      distribution. Myocardial biopsies in DCM reveal a chronic myocardial inflammatory
      process in almost 50% and myocardial persistence of adenoviral or enteroviral
      genome in about 15% of the patients. AIMS: We prospectively investigated whether
      the pattern of late gadolinium enhancement correlates with myocardial biopsy
      findings. METHODS AND RESULTS: 42 patients with DCM and 42 control subjects
      underwent contrast MRI. In the DCM group, endomyocardial biopsies were performed
      and evaluated for inflammation and viral genome. None of the control subjects
      showed late gadolinium enhancement whereas in 29 DCM patients (69%) gadolinium
      enhancement was detectable (p<0.001). 21 of the DCM patients (50%) showed midwall
      septal enhancement, 7 patients (17%) showed a patchy distribution of
      hyperenhancement and 1 patient (2%) showed enhancement typical for ischemic heart
      disease. In myocardial biopsy analysis, 2 patients (5%) showed persistence of
      viral genome, 18 patients (43%) showed inflammation and in 22 patients (52%)
      neither virus nor inflammation was detected. The pattern of late gadolinium
      enhancement and myocardial biopsy findings were not significantly correlated (p =
      0.854). CONCLUSION: MRI as a non-invasive technique cannot replace myocardial
      biopsy for the differential diagnosis of DCM.

PMID- 16111919
TI  - hUNC-93B1, a novel gene mainly expressed in the heart, is related to left
      ventricular diastolic function, heart failure morbidity and mortality in elderly
      men.
AB  - AIMS: The hUNC-93B1 gene has the highest expression in the heart. We aimed to
      explore relationships between the hUNC-93B1 gene and cardiac function, morbidity
      and mortality in elderly men. METHODS AND RESULTS: Two sub-samples of the
      population-based ULSAM-cohort (n=330, mean age 71 years and n=152, mean age 75
      years, respectively) were used to explore and validate relationships between
      genotypes of the hUNC-93B1 gene and cardiac phenotypes (ejection fraction, E/A
      ratio, left ventricular mass index and relative wall thickness). In the two
      samples, subjects homozygous for haplotype H3 had 34% and 35% higher level of E/A
      ratio compared to non-carriers (p=0.0002 and 0.017, respectively) independent of
      cardiovascular disease and medication. Using national cause-of-death and hospital
      discharge register data with 29 years of follow-up, no heart failure patients
      homozygous for haplotype H3 were hospitalised for heart failure before the age of
      75 years, compared to 25% for heterozygous and 55% for non-carriers (p<0.03). No
      homozygous subjects died during follow-up while 17% of the heterozygous and 15%
      of the non-carriers died (p=0.01). CONCLUSION: Haplotype H3 of the hUNC-93B1 gene
      seems related to E/A-ratio in elderly men. The relationship between the hUNC-93B1
      gene and the age at onset of heart failure and mortality support a view of a
      clinically relevant impact of the gene.

PMID- 16111920
TI  - Of mice and man: TLR11 (finally) finds profilin.
AB  - Toll-like receptors (TLRs) are primordial pathogen-recognition proteins that
      function as sentinels for the innate immune system. One of the TLR mysteries
      relates to TLR11, a receptor present in mice, but not humans, and known to
      recognize uropathogenic Escherichia coli. The first defined ligand for TLR11 has
      now been described as a profilin-like protein from Toxoplasma gondii. This
      discovery potentially gives us important clues as to how a gene expressed in
      mice, but not humans, actually relates to human infectious diseases.

PMID- 16111921
TI  - Image-guided cardiac cell delivery using high-resolution small-animal ultrasound.
AB  - Open-chest cardiac injection is the preferred delivery method for cardiac gene
      and stem cell therapy in small animals, but it is invasive and the operator is
      unable to see the actual delivery site. High-resolution ultrasound has recently
      been developed for small-animal imaging. We tested the hypothesis that image
      guided cardiac cell delivery using high-resolution ultrasound guidance is
      feasible and reproducible. Sprague-Dawley rats (n = 11) were imaged using high
      resolution ultrasound, and stably transfected cardiomyoblasts (plasmid-CMV
      firefly luciferase) were injected into the anterior cardiac wall under ultrasound
      guidance (parasternal long-axis view), using a 28-gauge needle. After injection,
      bioluminescence imaging was performed using a cooled charged-coupled camera.
      Injection was successful in all animals and was associated with no mortality. The
      signal detected was positively correlated with the amount of cells transplanted
      (R(2) = 0.94, P = 0.03) and highly correlated with ex vivo assays (R(2) = 0.82).
      In addition, the optical signal could be followed longitudinally using
      bioluminescence imaging. Ultrasound image-guided cardiac cell delivery is an
      effective, safe, and reproducible way to perform cell delivery to a specific
      myocardial region and can be combined with assessment of cardiac function. We are
      confident that the use of these technologies will play a significant role in the
      future of gene and cell therapy.

PMID- 16111922
TI  - Aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) expression in
      Baikal seal (Pusa sibirica) and association with 2,3,7,8-TCDD toxic equivalents
      and CYP1 expression levels.
AB  - Most toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related
      planar halogenated aromatic hydrocarbons (PHAHs) are mediated by ligand-activated
      aryl hydrocarbon receptor (AHR) signaling pathway. To understand the regulation
      mechanism of AHR and AHR nuclear translocator (ARNT) expression in wild Baikal
      seal (Pusa sibirica) population contaminated by PHAHs, the present study
      investigated hepatic mRNA expression levels of AHR and its heterodimer, ARNT
      genes, in association with biological index (age, gender and body weight), PHAH
      accumulation and expression levels of cytochrome P450 (CYP) 1A and 1B. While
      there was no gender difference, the AHR mRNA expression levels were increased
      with ages (p = 0.014) and body weights (p = 0.015), indicating that AHR
      expression might be affected by these biological factors. The AHR mRNA expression
      levels exhibited significant positive correlations with total TEQs and most of
      individual congener TEQs derived from polychorinated dibenzo-p-dioxins,
      dibenzofurans and non-ortho coplanar polychorinated biphenyls (PCBs), indicating
      the transcriptional up-regulation of AHR expression by these congeners. On the
      other hand, there was no significant correlation between individual TEQs from
      mono-ortho coplanar PCBs and AHR expression. These results imply the structure
      related transcriptional activity of AHR among PHAHs congeners. AHR mRNA levels
      showed positive correlations with both CYP1A protein (p = 0.039) and CYP1A1 mRNA
      expression levels (p = 0.046). In contrast to AHR expression, neither the total
      nor individual congener TEQs influenced ARNT at the transcriptional level. ARNT
      mRNA showed significant negative correlations with CYP1A/1B protein (p = 0.027
      and p = 0.006) and CYP1A1 mRNA expression levels (p = 0.039), implying the
      existence of different transcriptional regulation between AHR and ARNT genes and
      negative regulation by CYP1A/1B-mediated signaling pathways. The present findings
      may render significant insight on the basic mechanisms underlying regulation of
      AHR and ARNT expressions associated with biological factors and PHAH exposure in
      wild mammalian populations.

PMID- 16111923
TI  - Protective effects of silybin on human umbilical vein endothelial cell injury
      induced by H2O2 in vitro.
AB  - Oxidative injury induces cellular and nuclear damages that lead to cell injury.
      Agents or antioxidants that can inhibit production of reactive oxygen species can
      prevent injury. We tested the hypothesis that silybin can inhibit H2O2-induced
      injury in human umbilical vein endothelial cells. Eighteen hours of treatment
      with 750 micromol l(-1) H2O2 significantly stimulated expression of caspase-3 and
      cell apoptosis. In addition, it is observed that H2O2 increased the amounts of
      malondialdenhyde (MDA), the dehydrogenase (LDH) leakage, and decreased the
      activity of GSH-Px and NO contents in ECV-304 cells. In the H2O2 apoptosis model,
      the addition of 6.25-25 mg/L of silybin, which has in vitro radical scavenging
      activity, partially restored cell viability with a reduction in H2O2-induced
      apoptotic DNA damage, and decreased the expression of caspase-3. Moreover, it
      decreased other H2O2-induced damage in a concentration-dependent manner. The
      endothelial cell apoptosis was detected by AO/EB dual staining as well as flow
      cytometry, and the activity of pro-apoptotic factor caspase-3 was detected by
      immunocytochemical method. Our results suggest that the antioxidant, silybin,
      protects ECV-304 cells against H2O2-induced injury probably through its
      antioxidant activity, increasing the NO content, the activity GSH-Px and
      inhibiting signaling pathways mediated by caspase-3.

PMID- 16111924
TI  - Base excision repair by hNTH1 and hOGG1: a two edged sword in the processing of
      DNA damage in gamma-irradiated human cells.
AB  - Using siRNA technology, we down-regulated in human B-lymphoblastoid TK6 cells the
      two major oxidative DNA glycosylases/AP lyases that repair free radical-induced
      base damages, hNTH1 and hOGG1. The down-regulation of hOGG1, the DNA glycosylase
      whose main substrate is the mutagenic but not cytotoxic 8-oxoguanine, resulted in
      reduced radiation cytotoxicity and decreased double strand break (DSB) formation
      post-irradiation. This supports the idea that the oxidative DNA glycosylases/AP
      lyases convert radiation-induced clustered DNA lesions into lethal DSBs and is in
      agreement with our previous finding that overexpression of hNTH1 and hOGG1 in TK6
      cells increased radiation lethality, mutant frequency at the thymidine kinase
      locus and the enzymatic production of DSBs post-irradiation [N. Yang, H. Galick,
      S.S. Wallace, Attempted base excision repair of ionizing radiation damage in
      human lymphoblastoid cells produces lethal and mutagenic double strand breaks,
      DNA Repair (Amst) 3 (2004) 1323-1334]. Interestingly, cells deficient in hNTH1,
      the DNA glycosylase that repairs a major lethal single free radical damage,
      thymine glycol, were more radiosensitive but at the same time fewer DSBs were
      formed post-irradiation. These results indicate that hNTH1 plays two roles in the
      processing of radiation damages: repair of potentially lethal single lesions and
      generation of lethal DSBs at clustered damage sites. In contrast, in hydrogen
      peroxide-treated cells where the majority of free radical DNA damages are single
      lesions, the base excision repair pathway functioned to protect the cells. Here,
      overexpression of hNTH1 and hOGG1 resulted in reduced cell killing while
      suppression of glycosylase expression resulted in elevated cell death.

PMID- 16111925
TI  - Determination of the major mercapturic acids of acrylamide and glycidamide in
      human urine by LC-ESI-MS/MS.
AB  - We developed a LC-MS/MS method for the quantitative determination of the
      mercapturic acid (MA) metabolites of acrylamide (AA) AAMA and of its oxidative
      metabolite glycidamide (GA) GAMA in urine samples from the general population.
      The method requires 4 mL of urine which is solid phase extracted prior to LC
      MS/MS analysis. The metabolites are detected by ESI-tandem mass spectrometry in
      negative ionisation mode and quantified by isotope dilution. Detection limits
      ranged down to 1.5 microg/L urine for both AAMA and GAMA. The imprecision
      expressed as R.S.D. lay between 2% and 6% for both analytes (intra- and inter
      assay). First results on a small group of 29 persons out of the general
      population ranged from 5 to 338 microg/L AAMA and <LOD to 45 microg/L GAMA in
      urine. Only in one urine sample GAMA could not be detected. With this sensitive,
      reliable and rapid method we can determine the internal exposure of the general
      population to acrylamide in terms of the mercapturic acids. Especially the
      determination of GAMA is of great toxicological importance because GA is the
      ultimate carcinogenic agent in AA metabolism. The method therefore provides
      better insight into the metabolism of acrylamide in humans and furthermore
      supports risk assessments.

PMID- 16111926
TI  - Characterization and quantification of Bcl-2 antisense G3139 and metabolites in
      plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion
      trap mass spectrometry.
AB  - A novel ion-pair reversed phase electrospray ionization (IP-RP-ESI) liquid
      chromatography-mass spectrometry (LC-MS) method has been developed for
      identification and quantification of Bcl-2 antisense phosphorothioate
      oligonucleotides G3139 and metabolites in plasma. This method utilized solid
      phase extraction for desalting and matrix removal and detection by an ion trap
      mass spectrometer. Resolution was accomplished on a micro C18 column eluted with
      a mobile phase consisting of hexafluoro-2-propanol and triethylamine in methanol
      at 50 degrees C. Five G3139 metabolites were identified in plasma and urine from
      treated patients and rats. A cassette HPLC-MS/MS quantification method for G3139
      and three metabolites was developed and validated with a limit of quantification
      (LOQ) of 17.6 nM in human and rat plasma with acceptable precision and accuracy.
      Plasma pharmacokinetics of G3139 and metabolites in these species were described.

PMID- 16111927
TI  - Risk of hip/femur fractures in patients using antipsychotics.
AB  - The objective of our study was to investigate whether use of antipsychotics is
      associated with hip/femur fractures and whether pharmacological differences
      between antipsychotics are related to the occurrence of fractures. A case-control
      study was conducted, in which cases were defined as patients with a hip/femur
      fracture. Each patient was matched to one control patient. The association
      between use of antipsychotics and the occurrence of hip/femur fractures was
      evaluated using conditional logistic regression. The study included 44,500
      patients from 683 general practices from different geographical areas in the UK,
      registered within the General Practice Research Database (GPRD). Exposure to
      antipsychotics was categorized as "no use", "current use" and "prior use". Both
      current and prior use of antipsychotics were associated with an approximately two
      fold increased risk of fractures. After adjustment for possible confounders, a
      small significant effect remained (Odds Ratios (OR) of 1.3). We did not find an
      association between dose of antipsychotics, or between the degree of blockade of
      the alpha-1 adrenoceptor or histamine-1 receptor and risk of fractures. The total
      number of days of antipsychotic use was significantly associated with an
      increased risk of hip/femur fractures. We conclude that there is a small
      increased risk of hip/femur fractures associated with the use of antipsychotics.
      This risk increases with long-term use.

PMID- 16111928
TI  - Darwin's finches.

PMID- 16111929
TI  - Mechanics of animal movement.

PMID- 16111930
TI  - Chickens orient using a magnetic compass.

PMID- 16111931
TI  - Microtubules: Kar3 eats up the track.
AB  - Molecular motors are quintessential bio-machines found throughout phylogeny. A
      new application of in vitro assays highlights an unexpected dual functionality
      for the motor domain of the microtubule-based kinesin-14 type motor protein from
      budding yeast.

PMID- 16111932
TI  - Brain evolution: getting better all the time?
AB  - Recent studies on bats, goats and hominids suggest that some mammalian brains may
      have undergone dramatic evolutionary reductions in size. These studies emphasise
      the importance of selective pressures upon mammalian brain evolution and the need
      to integrate studies of neuroanatomy, neurophysiology and behaviour.

PMID- 16111933
TI  - Sexual selection: copycat mating in birds.
AB  - Female zebra finches may be influenced by the choices of other females when
      selecting mates, challenging the view that mate-choice copying should not occur
      in species with biparental care.

PMID- 16111934
TI  - Neural encoding: the brain's representation of space.
AB  - Recent studies have shown that a part of the brain makes use of a grid of
      equilateral triangles to encode the location of the animal within the local
      environment.

PMID- 16111935
TI  - Evolution: sex and cannibalism in redback spiders.
AB  - Female redback spiders cannibalise mating males. New research has shown they have
      evolved two separate sperm storage organs, allowing them to make post-copulatory
      paternity choices. Counter-adaptation by males, to maximise paternity after
      cannibalism, has led to the evolution of an abdominal constricting mechanism,
      which enhances short-term survival and mating success after attack by the female
      and maximises the chances of inseminating both sperm storage sites.

PMID- 16111936
TI  - Meiosis: organizing microtubule organizers.
AB  - During meiosis in fission yeast, the zygote nucleus undergoes microtubule-driven
      oscillatory movements that ultimately serve to promote genetic recombination. An
      essential component of this is a meiosis-specific consolidation of microtubule
      organizing activity to the the spindle pole body, driven by the novel coiled-coil
      protein mcp6/hrs1p.

PMID- 16111937
TI  - RNA turnover: unexpected consequences of being tailed.
AB  - In eukaryotic cells, the 3' poly(A) tails found on mRNA influence their stability
      and translation. The discovery of a second nuclear poly(A) polymerase complex has
      fueled a series of reports defining a new and unexpected role for 3' end poly(A)
      tails in the nuclear surveillance and turnover of noncoding RNAs and intergenic
      mRNAs of unknown function.

PMID- 16111938
TI  - Visual pursuit: an instructive area of cortex.
AB  - Recent experiments have revealed an area of visual cortex that provides a
      velocity error signal which enables the eye to learn to pursue targets when they
      move in a predictable way.

PMID- 16111939
TI  - Sec16 is a determinant of transitional ER organization.
AB  - BACKGROUND: Proteins are exported from the ER at transitional ER (tER) sites,
      which produce COPII vesicles. However, little is known about how COPII components
      are concentrated at tER sites. The budding yeast Pichia pastoris contains
      discrete tER sites and is, therefore, an ideal system for studying tER
      organization. RESULTS: We show that the integrity of tER sites in P. pastoris
      requires the peripheral membrane protein Sec16. P. pastoris Sec16 is an order of
      magnitude less abundant than a COPII-coat protein at tER sites and seems to show
      a saturable association with these sites. A temperature-sensitive mutation in
      Sec16 causes tER fragmentation at elevated temperature. This effect is specific
      because when COPII assembly is inhibited with a dominant-negative form of the
      Sar1 GTPase, tER sites remain intact. The tER fragmentation in the sec16 mutant
      is accompanied by disruption of Golgi stacks. CONCLUSIONS: Our data suggest that
      Sec16 helps to organize patches of COPII-coat proteins into clusters that
      represent tER sites. The Golgi disruption that occurs in the sec16 mutant
      provides evidence that Golgi structure in budding yeasts depends on tER
      organization.

PMID- 16111940
TI  - Implicitly evoked actions modulate visual selection: evidence from parietal
      extinction.
AB  - It has been proposed that the mental representation of a graspable object
      involves not only a description of its visual properties but also encodings of
      the motor programs to act upon it. Thus, observing a handle automatically primes
      the motor programs responsible for reaching and grasping it. Here, we provide
      neurological evidence that such action-related object features can bias visual
      selection. Two patients with visual extinction after right-parietal injury
      detected cups with left- or right-oriented handles, briefly displayed in either
      or both visual fields. People with this disorder have deficient awareness for
      stimuli toward the contralesional, left side of space, especially when competing
      stimuli appear further to the right. This contralesional extinction was
      significantly reduced when cups had handles affording a left-hand grasp, even
      though no hand response was required. No effect was found when handles were
      replaced with patches equated for position, size, and mean luminance. These data
      suggest that action-related information may be correctly extracted by the visual
      system, even though they are unavailable for conscious report. It is proposed
      that an object affordance for grasping modulates attentional selection by
      activating specific motor schema that, in turn, enhance the competitive strength
      of that object representation.

PMID- 16111941
TI  - Goal-driven behavioral adaptations in gap-climbing Drosophila.
AB  - Tasks such as reaching out toward a distant target require adaptive and goal
      oriented muscle-activity patterns. The CNS likely composes such patterns from
      behavioral subunits. How this coordination is done is a central issue in neural
      motor control. Here, we present a novel paradigm, which allows us to address this
      question in Drosophila with neurogenetic tools. Freely walking flies are faced
      with a chasm in their way. Whether they initiate gap-crossing behavior at all and
      how vigorously they try to reach the other side of the gap depend on a visual
      estimate of the gap width. By interfering with various putative distance
      measuring mechanisms, we found that flies chiefly use the vertical edges on the
      targeted side to distill the gap width from the parallax motion generated during
      the approach. At gaps of surmountable width, flies combine and successively
      improve three behavioral adaptations to maximize the front-leg reach. Each leg
      pair contributes in a different manner. A screen for climbing mutants yielded
      lines with defects in the control of climbing initiation and others with specific
      impairments of particular behavioral adaptations while climbing. The fact that
      the adaptations can be impaired separately unveils them as distinct subunits.

PMID- 16111942
TI  - Hrs1p/Mcp6p on the meiotic SPB organizes astral microtubule arrays for
      oscillatory nuclear movement.
AB  - Microtubules and the motor protein dynein play pivotal roles in the movement and
      positioning of the nucleus and cytoplasmic organelles in a cell. In fission
      yeast, oscillatory movement of the nucleus termed horsetail nuclear movement
      (HNM) has been observed during meiotic prophase. HNM is led by an astral
      microtubule array emanating from the spindle pole body (SPB), a centrosome
      equivalent organelle in yeasts, aided by the dynein-dynactin complex, and is
      proposed to facilitate the alignment of homologous chromosomes necessary for
      efficient meiotic recombination. Here we show that a meiosis-specific SPB
      component Hrs1p (also known as Mcp6p) is a key molecule to remodel microtubules
      into the horsetail-astral array (HAA). Deletion of Hrs1p impaired HAA formation,
      leading to compromised HNM. Ectopic expression of Hrs1p during the mitotic cell
      cycle resulted in the formation of a HAA-like astral microtubule array, which
      drove an oscillatory nuclear movement in interphase cells. Hrs1p interacted with
      components of the gamma-tubulin ring complex (gamma-TuRC) as well as with a
      meiotic SPB component. We propose that Hrs1p facilitates formation of the HAA,
      responsible for the vigorous HNM, by stabilizing connection between the SPB and
      minus ends of microtubules.

PMID- 16111943
TI  - Methylation protects miRNAs and siRNAs from a 3'-end uridylation activity in
      Arabidopsis.
AB  - Small RNAs of 21-25 nucleotides (nt), including small interfering RNAs (siRNAs)
      and microRNAs (miRNAs), act as guide RNAs to silence target-gene expression in a
      sequence-specific manner. In addition to a Dicer homolog, DCL1, the biogenesis of
      miRNAs in Arabidopsis requires another protein, HEN1. miRNAs are reduced in
      abundance and increased in size in hen1 mutants. We found that HEN1 is a miRNA
      methyltransferase that adds a methyl group to the 3'-most nucleotide of miRNAs,
      but the role of miRNA methylation was unknown. Here, we show that siRNAs from
      sense transgenes, hairpin transgenes, and transposons or repeat sequences, as
      well as a new class of siRNAs known as trans-acting siRNAs, are also methylated
      in vivo by HEN1. In addition, we show that the size increase of small RNAs in the
      hen1-1 mutant is due to the addition of one to five U residues to the 3' ends of
      the small RNAs. Therefore, a novel uridylation activity targets the 3' ends of
      unmethylated miRNAs and siRNAs in hen1 mutants. We conclude that 3'-end
      methylation is a common step in miRNA and siRNA metabolism and likely protects
      the 3' ends of the small RNAs from the uridylation activity.

PMID- 16111944
TI  - Evolution in action: following function in duplicated floral homeotic genes.
AB  - Gene duplication plays a fundamental role in evolution by providing the genetic
      material from which novel functions can arise. Newly duplicated genes can be
      maintained by subfunctionalization (the duplicated genes perform different
      aspects of the original gene's function) and/or neofunctionalization (one of the
      genes acquires a novel function). PLENA in Antirrhinum and AGAMOUS in Arabidopsis
      are the canonical C-function genes that are essential for the specification of
      reproductive organs. These functionally equivalent genes encode closely related
      homeotic MADS-box transcription factors. Using genome synteny, we confirm
      phylogenetic analyses showing that PLENA and AGAMOUS are nonorthologous genes
      derived from a duplication in a common ancestor. Their respective orthologs,
      SHATTERPROOF in Arabidopsis and FARINELLI in Antirrhinum, have undergone
      independent subfunctionalization via changes in regulation and protein function.
      Surprisingly, the functional divergence between PLENA and FARINELLI, is
      morphologically manifest in both transgenic Antirrhinum and Arabidopsis. This
      provides a clear illustration of a random evolutionary trajectory for gene
      functions after a duplication event. Different members of a duplicated gene pair
      have retained the primary homeotic functions in different lineages, illustrating
      the role of chance in evolution. The differential ability of the Antirrhinum
      genes to promote male or female development provides a striking example of
      subfunctionalization at the protein level.

PMID- 16111945
TI  - Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C.
      elegans.
AB  - Programmed cell death (PCD) is an essential and highly orchestrated process that
      plays a major role in morphogenesis and tissue homeostasis during development. In
      humans, defects in regulation or execution of cell death lead to diabetes,
      neurodegenerative disorders, and cancer. Two major types of PCD have been
      distinguished: the caspase-mediated process of apoptosis and the caspase
      independent process involving autophagy. Although apoptosis and autophagy are
      often activated together in response to stress, the molecular mechanisms
      underlying their interplay remain unclear. Here we show that BEC-1, the C.
      elegans ortholog of the yeast and mammalian autophagy proteins Atg6/Vps30 and
      Beclin 1, is essential for development. We demonstrate that BEC-1 is necessary
      for the function of the class III PI3 kinase LET-512/Vps34, an essential protein
      required for autophagy, membrane trafficking, and endocytosis. Furthermore, BEC-1
      forms a complex with the antiapoptotic protein CED-9/Bcl-2, and its depletion
      triggers CED-3/Caspase-dependent PCD. Based on our results, we propose that bec-1
      represents a link between autophagy and apoptosis, thus supporting the view that
      the two processes act in concerted manner in the cell death machinery.

PMID- 16111946
TI  - Two different types of light-dependent responses to magnetic fields in birds.
AB  - A model of magnetoreception proposes that the avian magnetic compass is based on
      a radical pair mechanism, with photon absorption leading to the formation of
      radical pairs. Analyzing the predicted light dependency by testing migratory
      birds under monochromatic lights, we found that the responses of birds change
      with increasing intensity. The analysis of the orientation of European robins
      under 502 nm turquoise light revealed two types of responses depending on light
      intensity: under a quantal flux of 8.10(15) quanta m(-2) s(-1), the birds showed
      normal migratory orientation in spring as well as in autumn, relying on their
      inclination compass. Under brighter light of 54.10(15) quanta m(-2) s(-1),
      however, they showed a "fixed" tendency toward north that did not undergo the
      seasonal change and proved to be based on magnetic polarity, not involving the
      inclination compass. When birds were exposed to a weak oscillating field, which
      specifically interferes with radical pair processes, the inclination compass
      response was disrupted, whereas the response to magnetic polarity remained
      unaffected. These findings indicate that the normal inclination compass used for
      migratory orientation is based on a radical-pair mechanism, whereas the fixed
      direction represents a novel type of light-dependent orientation based on a
      mechanism of a different nature.

PMID- 16111947
TI  - Stent placement or brachytherapy for palliation of dysphagia from esophageal
      cancer: a prognostic model to guide treatment selection.
AB  - BACKGROUND: Brachytherapy was found to be preferable to metal stent placement for
      the palliation of dysphagia because of inoperable esophageal cancer in the
      randomized SIREC trial. The benefit of brachytherapy, however, only occurred
      after a relatively long survival. The objective is to develop a model that
      distinguishes patients with a poor prognosis from those with a relatively good
      prognosis. METHODS: Survival was analyzed with Cox regression analysis. Dysphagia
      adjusted survival (alive with no or mild dysphagia) was studied with Kaplan-Meier
      analysis. Patient data is from the multicenter, randomized, controlled trial
      (SIREC, n = 209) and a consecutive series (n = 396). Patients received a stent or
      single-dose brachytherapy. RESULTS: Significant prognostic factors for survival
      included tumor length, World Health Organization performance score, and the
      presence of metastases (multivariable p < 0.001). A simple score, which also
      included age and gender, could satisfactorily separate patients with a poor,
      intermediate, and relatively good prognosis within the SIREC trial. For the poor
      prognosis group, the difference in dysphagia-adjusted survival was 23 days in
      favor of stent placement compared with brachytherapy (77 vs. 54 days, p = 0.16).
      For the other prognostic groups, brachytherapy resulted in a better dysphagia
      adjusted survival. CONCLUSIONS: A simple prognostic score may help to identify
      patients with a poor prognosis in whom stent placement is at least equivalent to
      brachytherapy. If further validated, this score can provide an evidence-based
      tool for the selection of palliative treatment in esophageal cancer patients.

PMID- 16111948
TI  - Stent vs. brachytherapy: does life expectancy help you decide?

PMID- 16111949
TI  - Endoscopic debridement of paraesophageal, mediastinal abscesses: a prospective
      case series.
AB  - BACKGROUND: Mediastinal abscesses after esophageal perforation or postoperative
      leakage nearly always require surgical intervention. METHODS: Patients with
      paraesophageal abscesses were treated with EUS-guided or endoscopic mediastinal
      puncture if the abscess was >2 cm and sepsis was present. Abscess cavities were
      entered with a 9.5-mm endoscope after balloon dilation to allow irrigation and
      drainage. Debris was removed with a Dormia basket. Concomitant pleural effusions
      were treated with transthoracic drains. Patients received intravenous antibiotics
      and enteral/parenteral nutrition. RESULTS: Twenty patients fulfilled the entry
      criteria. Simple drainage was sufficient in 4 cases, and puncture was impossible
      in one case. Of the 15 treated patients (age 39-76 years, 5 women) the etiology
      of perforation was Boerhaave's syndrome (n = 8), anastomotic leak (n = 3), and
      iatrogenic perforation (n = 4). Debridement was successful in all cases and
      required a median of 5 daily sessions (range 3-10). All patients became
      apyrexial, with a C-reactive protein < 5 mg/L within a median of 4 days (range 2
      8 days). Esophageal defects were closed with endoclips (n = 7), fibrin glue (n =
      4), metal stents (n = 1), or spontaneously healed (n = 3). One patient died from
      a massive pulmonary embolism one day after successful debridement (mortality 7%).
      No other complications were seen. Median follow-up was 12 months (range 3-40
      months). CONCLUSIONS: Nonoperative endoscopic transesophageal debridement of
      mediastinal abscesses appears safe and effective.

PMID- 16111950
TI  - The effects of eradication of Helicobacter pylori on the recurrence of duodenal
      ulcers in patients with cirrhosis.
AB  - BACKGROUND: The role of Helicobacter pylori in patients with cirrhosis and
      increased prevalence of peptic ulcers is still poorly defined. The objective is
      to evaluate the effect of H pylori eradication on ulcer recurrence in patients
      with cirrhosis. METHODS: The study was conducted at a single, tertiary, referral
      hospital with 1200 beds. Patients with cirrhosis and duodenal ulcers were tested
      for H pylori and were enrolled in the study. Patients with positive H pylori
      received eradication therapy. Patients with duodenal ulcers received
      antisecretory therapy and regular endoscopic examinations. Main outcome
      measurements were the recurrence of duodenal ulcers within 1 year. RESULTS: A
      total of 104 patients with cirrhosis and duodenal ulcers were enrolled. Fifty
      four patients (52%) were H pylori positive, and 50 patients (48%) were H pylori
      negative. Forty-four patients received antimicrobial treatment and 36 patients
      achieved eradication of H pylori. Recurrent duodenal ulcers within 1 year were
      noted in 21 of 36 patients (58%) who achieved H pylori eradication. Recurrent
      duodenal ulcers also were noted in 8 of the 18 patients (44%) who remained H
      pylori positive and in 24 of the patients (48%) who were H pylori negative since
      their enrollment in the study (p = 0.53). The limitation was a relatively small
      sample size. CONCLUSIONS: The results of our study showed that the prevalence of
      H pylori in patients with cirrhosis and duodenal ulcers was only 52%. Eradication
      of H pylori in patients with cirrhosis and duodenal ulcers did not effectively
      reduce the recurrence of ulcers.

PMID- 16111951
TI  - Peptic ulcer disease in patients with chronic liver disease: looking beyond bugs
      and drugs.

PMID- 16111952
TI  - Can MRCP replace the diagnostic role of ERCP for patients with choledochal cysts?
AB  - BACKGROUND: MRCP is rapidly replacing diagnostic ERCP in various
      pancreaticobiliary diseases. This study was designed to evaluate the accuracy of
      MRCP in detecting and determining the extent of choledochal cysts, as well as
      associated ductal anomalies or lesions. METHODS: The study design was an 8-year
      retrospective survey conducted at a tertiary referral center, Asan Medical Center
      (University of Ulsan College of Medicine, Seoul, Korea). There were 72 patients
      with choledochal cysts. All patients underwent both MRCP and ERCP. MRCP findings
      were compared with those of ERCP as the criterion standard. RESULTS: The overall
      detection rate of MRCP for choledochal cysts was 96% (69/72). The sensitivity,
      the specificity, the positive predictive value, and the negative predictive value
      of MRCP for classifying choledochal cysts according to Todani's classification
      were 81%, 90%, 86%, and 86% in type I, respectively; 73%, 100%, 100, and 95% in
      type III, respectively; 83%, 90%, 80%, and 91% in type IVa, respectively; 100%,
      100%, 100%, and 100% in type IVb, respectively; and 100%, 100%, 100%, and 100% in
      type V, respectively. The sensitivity, the specificity, and the accuracy of MRCP
      for detecting ductal anomalies were 83%, 90%, and 86%, respectively. The
      detection rate of MRCP for concurrent cholangiocarcinoma and choledocholithiasis
      was 87% (13/15) and 100% (8/8), respectively. CONCLUSIONS: MRCP showed overall
      good accuracy in the detection and the classification of choledochal cysts and
      revealed associated cholangiocarcinoma and choledocholithiasis with excellent
      accuracy. MRCP, therefore, may supersede the diagnostic role of ERCP for the
      patients with choledochal cysts. However, MRCP showed limited capacity to detect
      minor ductal anomalies or small choledochocele.

PMID- 16111953
TI  - Prospective, randomized, controlled trial of prophylactic pancreatic stent
      placement for endoscopic snare excision of the duodenal ampulla.
AB  - BACKGROUND: Tumors that arise in the region of the major duodenal papilla account
      for 5% of GI neoplasms and 36% of resectable pancreaticoduodenal tumors. There is
      limited published literature that addresses the safety of endoscopic excision of
      the papilla. Although there is consensus about prophylactic pancreatic-duct stent
      placement, there is little supporting prospective data. The aim of this
      randomized, controlled trial was to compare the rates of postsnare ampullectomy
      pancreatitis in patients who did/did not receive prophylactic pancreatic-duct
      stent placement. METHODS: Consecutive patients who were to undergo en bloc snare
      ampullectomy were randomized to placement of pancreatic-duct stent after
      ampullectomy or to no stent placement. RESULTS: In total, 19 patients were
      enrolled, and 10 received pancreatic stents. Postprocedure pancreatitis occurred
      in 3 patients in the 24 hours after endoscopy, all cases occurred in the
      unstented group, 33% vs. 0% (stented group), p = 0.02. Median peak amylase level
      was 3692 U/L (range 1819-4700 U/L) and median peak lipase level was 11450 U/L
      (range 5900-17,000 U/L). All 3 patients were hospitalized for a median of 2 days
      (range 1-6), and all made a complete recovery. CONCLUSIONS: Our findings suggest
      that a protective effect is conferred by pancreatic stent placement in reducing
      postampullectomy pancreatitis. Future large-scale studies are required to confirm
      this benefit.

PMID- 16111954
TI  - Endoscopic ampullectomy: does pancreatic stent placement make it safer?

PMID- 16111955
TI  - Diagnostic utility of peroral cholangioscopy for various bile-duct lesions.
AB  - BACKGROUND: We evaluated the utility of peroral cholangioscopy (POCS) for
      distinguishing malignant from benign biliary disease to cover low sensitivity of
      tissue sampling. METHODS: From February 1992 to April 2004, all consecutive
      patients who underwent POCS to confirm the etiology of biliary disorders were
      included in this study. Brushing cytology or endobiliary forceps biopsy also was
      performed. We analyzed the diagnostic accuracy of tissue sampling with or without
      POCS diagnosis. RESULTS: A total of 97 patients (66 men, 31 women; mean age 64.2
      years) were included. The final diagnosis was confirmed by surgical resection in
      44, clinical follow-up in 52, and cytologic study of ascitic fluid in one. On the
      basis of ERCP findings, there were 76 strictures and 21 filling defects. Forceps
      biopsy was performed in 25 patients, and brush cytology was performed in 68
      patients. In the remaining 4 patients (4 filling defects, which were identified
      as stones by POCS), tissue samplings were not carried out. ERCP/tissue sampling
      correctly identified 22 of 38 malignant strictures and all 35 benign lesions
      except in 3 patients with inadequate samples (accuracy, 78.0%; sensitivity,
      57.9%; specificity, 100%). The addition of POCS correctly identified all 38
      malignant strictures and 33 of 38 benign lesions (accuracy, 93.4%; sensitivity,
      100%; specificity, 86.8%). For the 21 filling defects observed by ERCP, POCS
      correctly diagnosed all 8 malignant diseases and 13 benign lesions. CONCLUSIONS:
      The addition of POCS to tissue sampling improves the diagnostic ability and
      covers for insufficient sensitivity. POCS is especially useful for diagnosing a
      filling defect.

PMID- 16111957
TI  - Should all pancreatic cystic lesions be resected? Cyst-fluid analysis in the
      differential diagnosis of pancreatic cystic lesions: a meta-analysis.

PMID- 16111956
TI  - Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a
      pooled analysis.
AB  - BACKGROUND: Pancreatic cystic tumors commonly include serous cystadenoma (SCA),
      mucinous cystadenoma (MCA), and mucinous cystadenocarcinoma (MCAC). A
      differential diagnosis with pseudocysts (PC) can be difficult. Radiologic
      criteria are not reliable. The objective of the study is to investigate the value
      of cyst fluid analysis in the differential diagnosis of benign (SCA, PC) vs.
      premalignant or malignant (MCA, MCAC) lesions. METHODS: A search in PubMed was
      performed with the search terms cyst, pancrea, and fluid. Articles about cyst
      fluid analysis of pancreatic lesions that contained the individual data of at
      least 7 patients were included in the study. Data of all individual patients were
      combined and were plotted in scatter grams. Cutoff levels were determined.
      RESULTS: Twelve studies were included, which comprised data of 450 patients.
      Cysts with an amylase concentration <250 U/L were SCA, MCA, or MCAC (sensitivity
      44%, specificity 98%) and, thus, virtually excluded PC. A carcinoembryonic
      antigen (CEA) <5 ng/mL suggested a SCA or PC (sensitivity 50%, specificity 95%).
      A CEA >800 ng/mL strongly suggested MCA or MCAC (sensitivity 48%, specificity
      98%). A carbohydrate-associated antigen (CA) 19-9 <37 U/mL strongly suggested PC
      or SCA (sensitivity 19%, specificity 98%). Cytologic examination revealed
      malignant cells in 48% of MCAC (n = 111). DISCUSSION: Most pancreatic cystic
      tumors should be resected without the need for cyst fluid analysis. However, in
      asymptomatic patients, in patients with an increased surgical risk, and, in
      patients in whom there is a diagnostic uncertainty about the presence of a PC,
      cyst fluid analysis helps to determine the optimal therapeutic strategy.

PMID- 16111958
TI  - Performance of antegrade double-balloon enteroscopy: comparison with push
      enteroscopy.
AB  - BACKGROUND: Double-balloon enteroscopy (DBE) is a novel procedure for the
      diagnosis of small-bowel pathology. The aim of this retrospective study was to
      compare the performance and the diagnostic value of antegrade DBE with those of
      push enteroscopy (PE). METHODS: We reviewed endoscopic and histologic findings in
      118 patients examined by PE or antegrade DBE during a period 1980 to 2004. The
      maximal length of insertion under plain radiograph was compared between patients
      examined by PE and those examined by antegrade DBE. Diagnostic yield was compared
      among patients stratified by indication for enteroscopy and the duodenal
      pathology. RESULTS: Ninety-one patients were examined by PE and 27 patients by
      antegrade DBE. Length of insertion from the ligament of Treitz was significantly
      greater in antegrade DBE (median, 92 cm; range, 40-144 cm) than in PE (median, 22
      cm; range, 0-98 cm; p < 0.0001). In 90 nonbleeding patients with inflammatory or
      miscellaneous diseases or polyposis, the diagnostic yield was not different
      between PE and antegrade DBE (64% vs. 82%, p = 0.13). However, it was higher in
      antegrade DBE (79%) than in PE (31%, p = 0.012) in nonbleeding patients without
      duodenal pathology. In bleeding patients, the diagnostic yield was 40% in
      antegrade DBE and 36% in PE (p = 0.61). CONCLUSIONS: Antegrade DBE is superior to
      PE in exploration of the small intestine and in diagnostic yield for small
      intestinal pathology.

PMID- 16111959
TI  - Prospective study of the clinical impact of EUS.
AB  - BACKGROUND: Studies on the clinical impact of EUS are lacking. The aim of this
      study was to examine the impact of EUS on the management plans by referring
      doctors and patient outcomes. METHODS: Consecutive patients undergoing EUS
      between August 2002 and June 2004 were prospectively studied. Referring doctors
      were given a pre-EUS questionnaire that asked about provisional diagnosis and
      management plan. A post-EUS questionnaire was sent 6 weeks after the procedure.
      RESULTS: A total of 330 patients were examined, and completed questionnaires were
      received in 70%. EUS-guided FNA was performed in 69 (30%) patients. EUS resulted
      in a change in diagnosis and management in 26% and 48% of cases, respectively.
      Thirty-nine of the latter patients (33%) avoided unnecessary surgery. In 50% of
      cases, additional investigations were avoided. Doctors reported EUS as very or
      moderately useful in 210 patients (91%). Doctors of 223 patients (97%) reported
      that they would use EUS again. CONCLUSIONS: The use of EUS had a significant
      clinical impact on patients. EUS resulted in a change of diagnosis in a fourth of
      patients and a change in management in half of patients studied.

PMID- 16111960
TI  - The skeptical endoscopist.

PMID- 16111961
TI  - The interview.

PMID- 16111962
TI  - EUS-guided Trucut biopsy.

PMID- 16111964
TI  - Combined endoscopic cautery and clip closure of chronic gastrocutaneous fistulas.
AB  - BACKGROUND: Chronic gastrocutaneous fistula with intermittent drainage is a
      common outcome after removing long-standing gastrostomy tubes. The standard
      treatment is surgery with laparotomy and excision of the fistula tract. This
      study describes the results of an endoscopic closure technique by using a
      combination of electrocautery and metal clips. METHODS: Three patients with
      gastrocutaneous fistulas (duration 3 months to 3 years) after gastrostomy tube
      removal were treated endoscopically by electrocautery of the tract and
      application of metal clips. OBSERVATIONS: Treatment resulted in complete fistula
      closure in two patients and partial closure in a third patient. CONCLUSIONS:
      Combined endoscopic therapy with electrocautery and clipping may be an
      alternative to surgical closure of chronic gastrocutaneous fistulas.

PMID- 16111963
TI  - Rigiflex pneumatic dilation of achalasia without fluoroscopy: a novel office
      procedure.
AB  - BACKGROUND: Pneumatic balloon dilation is the most effective nonsurgical
      treatment to relieve functional obstruction of the gastroesophageal junction in
      achalasia. Since its inception, the conventional technique has been performed
      under direct fluoroscopic control with or without a guidewire. To overcome the
      impediments of the conventional technique and radiation exposure, we have devised
      a novel technique of achalasia dilation without fluoroscopy. The aim of the study
      was to evaluate the efficacy, the safety, and the outcome of the new method.
      METHODS: Fifty-six patients (34 men, 22 women) (mean age 32 years) with achalasia
      cardia were subjected, over a span of 2 years, to dilation with a Gruntzig-type
      (Rigiflex balloon) pneumatic dilator with the new technique. Clinical response
      and complications were assessed. OBSERVATIONS: Excellent improvement in
      dysphagia, pain, and regurgitation was observed in 92.9%, 89.3%, and 89.3%
      patients at 24 hours, 6 weeks, and 6 months after dilation, respectively. The
      mean time to maneuver the Rigiflex balloon to the antrum was 30 seconds. The
      procedure was successfully done in all patients, and there were no procedural
      failures. The mean time of the procedure was 8 minutes. There were no
      complications or mortality during the study. CONCLUSIONS: Achalasia dilation with
      this new technique has excellent results and is devoid of the side effects of
      radiation. It can be done as an office procedure, without the need of a
      fluoroscopy setup.

PMID- 16111965
TI  - Self-expandable stents in malignant colonic obstruction: insertion assisted with
      a sphincterotome in technically difficult cases.
AB  - BACKGROUND: Stent placement is effective in relieving malignant colonic
      obstruction. Nevertheless, the technique may offer difficulties in sharply
      angulated lesions. METHODS: Guidewire insertion assisted with a sphincterotome
      was performed in 4 patients with intestinal obstruction caused by malignant
      colonic strictures. The manipulation of the sphincterotome by turning and bending
      its tip allows the cannulation of the lesion with the guidewire and, as a
      consequence, the stent insertion. OBSERVATIONS: The procedure was successfully
      performed in 4 technically difficult cases in which it had been impossible to
      pass the guidewire with the standard catheter. CONCLUSIONS: In technically
      difficult cases, with the use of a sphincterotome, insertion of the guidewire
      appears to be easier. This new method may improve technical success rates in
      stent placement.

PMID- 16111966
TI  - A combat-related foreign body.

PMID- 16111967
TI  - Diagnosis of small-bowel ischemic necrosis by capsule endoscopy.

PMID- 16111968
TI  - Double-balloon endoscopy for ileal GI stromal tumor.

PMID- 16111970
TI  - Primary mucosa-associated lymphoid tissue lymphoma occurring in the rectum.

PMID- 16111969
TI  - Cecal ameboma.

PMID- 16111972
TI  - Confined progression of cap polyposis along the anastomotic line, implicating the
      role of inflammatory responses in the pathogenesis.

PMID- 16111971
TI  - Voluminous juxtapapillary gangliocytic paraganglioma.

PMID- 16111973
TI  - Initial experience of videocapsule endoscopy for diagnosing small-bowel tumors in
      patients with GI polyposis syndromes.
AB  - BACKGROUND: Small-bowel tumors frequently occur in familial adenomatous polyposis
      and other GI polyposis syndromes. These tumors are difficult to detect with
      conventional techniques. Our aim was to assess the utility of videocapsule
      endoscopy in the detection of small-bowel tumors in this setting. METHODS: We
      examined 19 familial adenomatous polyposis patients and 3 patients with either
      Peutz-Jeghers syndrome, hyperplastic polyposis, or Cowden disease. OBSERVATIONS:
      Prevalence of small-bowel polyps on videocapsule endoscopy was 59% in all
      patients, 52.6% in familial adenomatous polyposis patients, and 75% in a subgroup
      of familial adenomatous polyposis patients with exon 15 mutations. Videocapsule
      endoscopy was safe and well tolerated in all patients. CONCLUSIONS: Videocapsule
      endoscopy has a high yield in detecting small-bowel tumors in patients with GI
      polyposis syndromes. It may be especially indicated in familial adenomatous
      polyposis patients with the aggressive phenotype of the disease, e.g., mutations
      in exon 15.

PMID- 16111974
TI  - Colonoscopic diagnosis of mucocele of the appendix.
AB  - BACKGROUND: Appendiceal mucoceles are uncommon cystic neoplasms characterized by
      distension of the appendiceal lumen with mucus. There have been no reported
      series of colonoscopically diagnosed mucoceles with clinicopathologic
      correlation. METHODS: A retrospective review of colonoscopies performed at our
      institution over the past 14 years was undertaken with patient demographics,
      clinical data, surgical outcomes, and histopathology obtained from hospital
      records. OBSERVATIONS: Seven patients (6 women) with mucocele of the appendix
      were identified at colonoscopy. Three had complained of right lower quadrant
      pain. All 7 patients underwent surgical resection. Histopathology demonstrated
      mucinous cystadenoma in all. No cases revealed carcinoma, and there have been no
      deaths related to the mucocele. CONCLUSIONS: Appendiceal mucoceles may be
      recognized at colonoscopy as a smooth bulbous submucosal lesion of the cecum with
      an impression formed by the appendiceal orifice. Recognition at colonoscopy is
      important because it enables accurate diagnosis and directs management. Surgery
      is recommended in all cases given the risk of malignancy or perforation with
      resultant pseudomyxoma peritonei.

PMID- 16111975
TI  - Transient thoracic duct obstruction: evaluation by EUS.

PMID- 16111976
TI  - EUS-guided FNA of a peripancreatic lymphocele.

PMID- 16111977
TI  - Retrieval of a retained capsule endoscope by double-balloon enteroscopy.

PMID- 16111978
TI  - Multifocal mucosa-associated lymphoid tissue lymphoma presenting as lower-GI
      bleeding.

PMID- 16111979
TI  - Role of hemoclips in a patient with cecal angiodysplasia at high risk of
      recurrent bleeding from antithrombotic therapy to maintain coronary stent
      patency: a case report.

PMID- 16111980
TI  - Diagnosis of focal metastasis to the adrenal gland by EUS-guided core biopsy.

PMID- 16111982
TI  - Peroral transgastric endoscopic ligation of fallopian tubes with long-term
      survival in a porcine model.

PMID- 16111983
TI  - Laryngeal jack-assisted endoscopic management of postcricoid esophageal
      obstruction.

PMID- 16111985
TI  - The refractory and the recurrent esophageal stricture: a definition.

PMID- 16111986
TI  - Impacted biliary basket.

PMID- 16111987
TI  - Gender-related changes in the pancreas detected by EUS.

PMID- 16111989
TI  - Emergency preparedness: concept development for nursing practice.
AB  - Emergency preparedness is a concept frequently referred to within medical and
      psychological literature and in local, state, and federal documents, yet it is
      not well defined. There is no published theoretical or operational definition of
      the term, and no conceptual analysis of the phenomena of emergency preparedness
      exists within the literature.Because nursing is the single largest health
      professional resource for response, work toward further refinement of the concept
      of emergency preparedness has relevance for nursing practice. This article
      examines and attempts to clarify the concept of emergency preparedness,especially
      as it applies to nursing.

PMID- 16111990
TI  - The impact of disaster on culture, self, and identity: increased awareness by
      health care professionals is needed.
AB  - Self, identity, and culture are important psychosocial concepts in the analysis
      of how individuals perceive self in social context, self across the lifespan, and
      self in relation to cultural context. Contemporary theories emphasize the
      importance of a holistic perspective and promote the idea of identity as opposed
      to self-concept. This article explores the application of these ideas to
      disasters to provide guidance for health care professionals on how disasters
      impact individuals, groups, and communities. Disasters have a major impact on
      social infrastructure and culture, and in turn result in a range of human
      responses. Placing identity and maintenance of cultural integrity at the heart of
      practice,health care professionals are encouraged to take a holistic perspective
      across all phases of the disaster. Individuals, groups, and communities exhibit a
      range of responses influenced by levels of vulnerability or resilience.
      Facilitating expression of feelings related to the disaster experience is an
      important focus for health care. Always working within the cultural context and
      being sensitive to the rituals related to remembering and mourning help preserve
      dignity and possibly facilitate creation of a new identity and a revised culture
      after a disaster.

PMID- 16111991
TI  - Disaster nursing curriculum development based on vulnerability assessment in the
      pacific northwest.
AB  - Disasters caused by naturally occurring or deliberately caused infections, toxic
      chemical spills, radiologic releases, or other catastrophic events are likely to
      challenge the US health care system and pose special risks to vulnerable groups.
      Despite these threats in the environment,most US nursing programs lack disaster
      nursing content. This article describes disaster nursing competencies needed in
      Washington State based on standards, local geographic and population
      vulnerabilities,expert review, and surveys of nursing students and practicing
      nurses. Disaster nursing competencies included the following categories:
      (1)providing for patient care needs; (2) practicing safely; (3)
      preparing,implementing, and evaluating institutional and community protocols in
      preparation for a disaster; (4) reporting and communicating; and (5)accessing up
      to-date information. Practicing nurses and student nurses indicated a strong need
      for disaster nursing content; the greatest perceived need was for content related
      to caring for injured or ill patients and practicing safely during a disaster.

PMID- 16111992
TI  - Disaster competency development and integration in nursing education.
AB  - Nurses, because of their nursing education and perspective practicing in multiple
      roles and settings, are uniquely qualified for mass casualty preparedness and
      response. Educating the current 2.7 million registered nurses and all future
      nursing graduates is a daunting task. Nursing education must ensure that
      graduates are prepared with the necessary knowledge and skills for mass casualty
      incidents. Four key entities are essential for education's successful
      implementation of disaster preparedness: education and professional
      organizations, accreditation and regulatory bodies, schools of nursing, and
      continuing education providers. This article examines the role each of these key
      entities plays in the development of a nursing workforce prepared for mass
      casualty response. In addition, the International Nursing Coalition for Mass
      Casualty Education (INCMCE) registered nurse (RN) competencies for mass casualty
      incidents and guidelines for integrating these competencies into the nursing
      education curricula are presented.

PMID- 16111993
TI  - A national curriculum for nurses in emergency preparedness and response.
AB  - Preliminary and continuing education concerning emergency preparedness is needed
      for nurses. Although some nurses have had natural disaster training, most have
      not had training to respond to bioterrorism events. Several organizations are
      working to develop standards and curricula for such training. This article
      highlights these efforts.

PMID- 16111994
TI  - Homeland security challenges in nursing practice.
AB  - Nurses need a comprehensive knowledge of doctrine, laws, regulations,programs,
      and processes that build the operational framework for health care preparedness.
      Key components of this knowledge base reside in the areas of: evolution of
      homeland security: laws and mandates affecting health care and compliance and
      regulatory issues for health care organizations. This article addresses primary
      components in both of these areas, after first assessing the status of nursing's
      involvement (in homeland security), as portrayed in the professional literature.

PMID- 16111995
TI  - The role of public health nursing in emergency preparedness and response.
AB  - Public health services are vital to homeland security and defense, and nurses
      make up the majority of public health care workers. This article identifies
      issues in preparing for bioterrorism and describes the role of public health
      nurses in bioterrorism preparedness.

PMID- 16111996
TI  - The role of the nurse practitioner in disaster planning and response.
AB  - Advanced practice nurses (APNs) and nurse practitioners (NPs) have provided
      health care services during disasters; however, little appears in the literature
      about their role. APNs and NPs represent a significant portion of the nursing
      workforce. This article focuses on critical factors to consider when preparing
      and planning for the role of NPs.

PMID- 16111997
TI  - Practical considerations for providing pediatric care in a mass casualty
      incident.
AB  - Children have unique physiologic and developmental characteristics that need to
      be considered. Plans for pediatric care during mass casualty incidents (MCIs)
      need to be developed. This article highlights challenges in providing care to
      children after MCIs and provides considerations for providing pediatric care.

PMID- 16111998
TI  - Disaster care: psychological considerations.
AB  - Disasters are tragic events that disrupt the normal functioning ofa community and
      overwhelm personal and community resources. The people who experience or simply
      witness traumatic events can be affected emotionally and develop a range of
      physical and emotional responses, which in turn can produce psychological,
      social, and physiological dysfunction. The challenge for health care providers is
      to recognize the range of emotions and to be able to identify when professional
      help is indicated. This article provides an overview of the human stress response
      and describes sources of stress that follow disasters, acute stress disorder,
      post-traumatic stress disorder, and interventions and resources used to care for
      victims after disasters.

PMID- 16111999
TI  - Research issues in preparedness for mass casualty events, disaster, war, and
      terrorism.
AB  - This article provides a perspective on the types of research questions that might
      be explored and strategies used in relation to disaster,terrorism, and mass
      casualty events. Research is addressed in the context of three areas of focus:
      issues related to the health care provider; issues affecting the patient,
      individual, family, and community; and issues related to the health care system.

PMID- 16112000
TI  - Hospital response to acute-onset disasters: the state of the science in 2005.
AB  - The level of emergency preparedness in US hospitals is a concern in light of the
      steady threat of natural disasters, transportation and industrial accidents, and
      the possibility of terror attack resulting in mass casualties. The science of
      hospital emergency preparedness is in an early stage of development. For research
      to logically expand knowledge, an accurate assessment--or examination of the
      state of the science--is conducted to determine the current state of knowledge,
      gaps in knowledge, and opportunities for future research. Milsten reviewed the
      literature on hospital response to acute-onset disasters from 1977 to 1999. His
      review of 107 articles contains research studies, case studies,and lessons
      learned pieces largely published in the medical literature.Milsten's analysis
      provides a substantial starting point. This article examines Milsten's review,
      identifies articles that have been published that add to this knowledge base, and
      identifies additional phenomena of interest.

PMID- 16112001
TI  - The human factors in a disaster.
AB  - Although natural disasters are claiming fewer lives now than even as recently as
      30 years ago, they remain responsible for many premature deaths, most in third
      world countries. This article highlights the relationship of human factors that
      can be found with third-world disasters and reviews interventions that have been
      used to reduce illness, injuries and deaths.

PMID- 16112002
TI  - Hereditary ovarian cancer.
AB  - Family history is the strongest risk factor for ovarian cancer. Three clinical
      manifestations of hereditary ovarian cancer have been recognized: (1) "site
      specific" ovarian cancer, (2) the breast and ovarian cancer syndrome, and (3) the
      hereditary nonpolyposis colorectal cancer (HNPCC; Lynch II) syndrome. The first 2
      groups are associated with germ line mutations in the BRCA1 and BRCA2 tumor
      suppressor genes, whereas HNPCC is associated with germ line mutations in the DNA
      mismatch repair (MMR) genes, primarily hMLH1 and hMSH2. At least 10% of all
      epithelial ovarian cancers are hereditary, with mutations in the BRCA genes
      accounting for approximately 90% of cases and most of the remaining 10%
      attributable to HNPCC. Hereditary ovarian cancers exhibit distinct
      clinicopathologic features compared with sporadic cancers. The cumulative
      lifetime risk of ovarian cancer is 40% to 50% for BRCA1 mutation carriers and 20%
      to 30% for BRCA2 mutation carriers. Both BRCA proteins participate in
      transcriptional regulation of gene expression as well as the recognition or
      repair of certain forms of DNA damage, particularly double-strand breaks.
      Mutations of BRCA1 and BRCA2 are mainly of the frameshift or nonsense variety.
      Most ovarian cancers associated with germ line BRCA mutations are diagnosed at a
      younger age and are high-grade and advanced-stage serous carcinomas. BRCA
      mutations do not seem to play a significant role in the development of mucinous
      or borderline ovarian tumors. Hereditary ovarian cancers have a distinctly better
      clinical outcome with longer overall survival and recurrence-free interval after
      chemotherapy than sporadic cancers. Women with a family history including 2 or
      more first- or second-degree relatives with either ovarian cancer alone or both
      breast and ovarian cancers should undertake prophylactic oophorectomy immediately
      after childbearing has been completed to reduce the risk of ovarian cancer. The
      cumulative risk of ovarian cancer in HNPCC families is more than 12%. Ovarian
      cancer in HNPCC syndrome is diagnosed at younger age than in the general
      population. Most tumors are low-stage well-differentiated or moderately
      differentiated carcinomas. Annual follow-up is recommended for these patients.

PMID- 16112003
TI  - Pigmented neurofibroma: review of Japanese patients with an analysis of
      melanogenesis demonstrating coexpression of c-met protooncogene and
      microphthalmia-associated transcription factor.
AB  - Pigmented neurofibroma (PNF) is a rare variant of neurofibroma showing melanin
      production. To clarify the clinicopathologic features of PNF and to characterize
      melanogenesis in PNF, 12 cases of PNF were examined in comparison with schwannoma
      (SCH, n = 16) and neurofibroma (NF, n = 26). The PNF patients were all Japanese
      including 7 men and 5 women, and patient age ranged from 11 to 71 years (median,
      23.5 years). They showed strong a predisposition for neurofibromatosis type 1.
      Their tumor size was large, and tumors arose from various sites of skin.
      Histologically, clusters of epithelioid, dendritic, and spindle melanin-producing
      cells with faint pigmentation had a tendency to locate in deep dermis and
      subcutis, which seems to be a characteristic pattern of melanogenesis. There was
      a transition between melanin-producing cells and Schwann cells.
      Immunohistochemical examination included known melanogenic markers,
      microphthalmia-associated transcription factor (MITF), which is a key regulator
      of melanogenesis, and 2 tyrosine kinase receptors, c-Met and c-Kit, which
      regulate the development of melanocytes. In PNF, melanin-producing cells were
      S100 (+), MITF (+), Melan-A (+), tyrosinase (+/-), HMB45 (+/-), c-Met (+), and c
      Kit (-). Schwann cells were S100 (+), MITF (-), Melan-A (-), tyrosinase (-),
      HMB45 (-), c-Met (-), and c-Kit (-), and intermediate spindle cells were S100
      (+), MITF (+), Melan-A (+), tyrosinase (-), HMB45 (-), c-Met (+), and c-Kit (-).
      When compared with SCH and NF, MITF was weakly expressed in a part of tumor cells
      of SCH, whereas no definite staining was found in NF. c-Met expression was very
      weak in a scattered manner in SCH (10/15 cases) and NF (10/26 cases). These
      results suggest that PNF is a unique tumor that shows differentiation toward
      mature melanin production, but ability of melanin synthesis seems to be impaired.
      There may be a close relationship between up-regulated MITF and c-Met and the
      peculiar melanogenic nature of PNF, and both of these are useful diagnostic tools
      for distinguishing PNFs with less melanin production from NFs.

PMID- 16112004
TI  - Splenic large B-cell lymphoma in patients with hepatitis C virus infection.
AB  - Hepatitis virus infection, especially type C (hepatitis C virus [HCV]), has been
      suggested to be one of the important pathogenetic factors for low- and high-grade
      B-cell lymphoma, including splenic marginal zone lymphoma (SMZL), in southern
      Europe. Here, we analyzed the incidences of HCV and hepatitis B virus (HBV)
      infections, and the clinicopathologic features in 29 cases of splenic diffuse
      large B-cell lymphoma (DLBCL), 10 SMZL, 3 splenic mantle cell lymphoma, 1 hairy
      cell leukemia, 13 B-chronic lymphocytic leukemia, and 12 hepatosplenic T-cell and
      natural killer cell lymphoma. Fifteen (51.7%) splenic DLBCL cases were HCV
      antibody-positive, and another 6 (20.7%) had the HBsAg. The incidence of each was
      significantly (P < .01) higher than those of HCV (9.3%) and HBV (1.9%) infections
      in 54 node-based DLBCL cases. Four examined HCV-positive DLBCL cases showed no
      type II cryoglobulinemia. HCV RNA was detected in fresh tumor tissues from 6 of 7
      examined DLBCL cases, and HBV DNA was present in another 2, as evaluated by real
      time polymerase chain reaction. Immunohistologically, tumor cells in 5 of 7
      examined DLBCL cases showed intracytoplasmic reactions for HCV NS3 and E2
      proteins and the viral receptor CD81. Of 6 cases, 2 showed an intranuclear
      reaction for the HBV surface protein. By Southern blot analysis, no rearrangement
      of the Bcl2 gene was detected in the tumor tissue of 7 HCV-positive DLBCL cases.
      For the other types of malignant lymphoma, 1 case each of SMZL (10%) and
      hepatosplenic T-cell and natural killer cell lymphoma (8.3%) showed HCV
      infection. In conclusion, persistent human hepatitis virus infections, especially
      HCV, may play an important role in the tumorigenesis of splenic DLBCL in Japan.

PMID- 16112005
TI  - Claudin expression in gastric adenocarcinomas: a tissue microarray study with
      prognostic correlation.
AB  - The claudins comprise a multigene family of integral membrane proteins, which
      play a major role in tight junction formation. Aberrations in the expression of
      certain claudins have been described in a number of malignancies. Our aims were
      to determine the expression pattern of claudins 1, 3, and 4 as well as ZO-1 in a
      large series of US patients with gastric cancer and to correlate expression with
      clinicopathologic and prognostic variables. Tissue microarrays were created from
      paraffinized samples from 146 patients with distal gastric adenocarcinomas (61
      intestinal and 85 diffuse or mixed subtypes). In addition, cores of normal mucosa
      and intestinal metaplasia were taken from most cases. The microarrays were
      stained for claudins 1, 3, and 4 and ZO-1, and the intensity of staining was
      determined using a 3-point scale. Moderate claudin 1 and ZO-1 membranous staining
      were present, whereas only focal weak claudin 3 and 4 membranous staining was
      present in normal gastric epithelium. Moderate to strong staining of claudins 1,
      3, 4, and ZO-1 was detected in 74%, 48%, 62%, and 74% of the intestinal but in
      only 46%, 24%, 45%, and 36% of the diffuse subtype of adenocarcinomas (P < .05).
      Cox multivariate analysis revealed that tumor stage, diffuse subtype, and
      moderate to strong claudin 4 staining were associated with decreased survival (P
      < .02). In conclusion, claudins 1, 3, and 4 and ZO-1 are strongly expressed in
      most gastric intestinal-type adenocarcinomas but less frequently in diffuse
      gastric cancers. The up-regulation of claudin expression during gastric
      carcinogenesis suggests their potential utility as diagnostic biomarkers and
      possible targets for therapeutic intervention.

PMID- 16112006
TI  - Clonal relationship of tumor nodules in hepatocellular carcinoma: a hierarchical
      clustering analysis of comparative genomic hybridization data.
AB  - Information on the clonal relationship between tumor nodules in patients
      diagnosed with hepatocellular carcinoma (HCC) holds prognostic significance in
      the prediction of recurrence and postoperative treatment. Here, we investigated
      the clonal relationships in 11 focal nodules from 5 patients with HCC by
      comparative genomic hybridization (CGH) and spectral karyotyping. CGH analysis
      indicated tumor nodules in 5 (100%) of 5 cases to share similar patterns of
      genomic imbalances, suggesting nodules to be clonally related. This clonal
      relationship was further substantiated in 2 cases, where spectral karyotyping
      analysis indicated identical structural rearrangements between focal tumors. Few
      studies have attempted to differentiate multicentric growth from intrahepatic
      dissemination in HCC using CGH analysis; however, data interpretation remained
      subjective. In this study, we have extended our data to include published CGH
      findings on 57 nodules derived from 19 HCC cases. Simulation of CGH findings by
      unsupervised 2-way hierarchical clustering indicated tumor nodules in 20 (83.3%)
      of 24 cases to cluster concordantly, signifying a high incidence of clonal
      similarity. In sum, bioinformatic analysis of genomic profiles may represent a
      reliable research tool in analyzing clonal relationships among tumor nodules.

PMID- 16112007
TI  - Minichromosome maintenance proteins 2 and 5 expression in muscle-invasive
      urothelial cancer: a multivariate survival study including proliferation markers
      and cell cycle regulators.
AB  - Evaluation of cell cycle regulators has gained special interest in the effort to
      increase the amount of prognostic information in malignant tumors. Minichromosome
      maintenance proteins (MCMs) drive the formation of prereplicative complexes,
      which is the first key event during G1 phase. Therefore, altered MCM expression
      may be a hallmark of cell cycle deregulation, which is supposed to be the most
      essential mechanism in the development and progression of bladder cancer. Our aim
      was to investigate the value of MCMs as proliferation markers and prognostic
      indicators in detrusor muscle-invasive urothelial bladder carcinomas. We analyzed
      immunohistochemically the expression of MCM-2 and MCM-5 in 65 patients with
      detrusor muscle-invasive urothelial bladder carcinomas in relation with
      clinicopathologic parameters, patients' overall and disease-free survival, and
      the expression of the conventional proliferation index Ki-67 and other cell cycle
      modulators (p53, pRb, p21(WAF1), and p27(Kip1)). The levels of MCM-2 and MCM-5
      were significantly higher in high-grade (P < .0001), advanced-stage (P = .001),
      and nonpapillary tumors (P < .0001). The expression of MCM-2 and MCM-5
      significantly associated with the conventional proliferation index Ki-67 (P =
      .0001 for each protein). The expression of MCM-2 or MCM-5 positively correlated
      with p53 labeling index (P = .014 and P = .009, respectively). Also, median
      p21(WAF1) labeling index was higher in MCM-5 high expressors (P = .028). Finally,
      both MCM-2 and MCM-5 associated significantly with adverse patients' outcome in
      both univariate (P = .0072 and P = .0074, respectively) and multivariate (P =
      .0001) analysis. In conclusion, MCM-2 and MCM-5 appear to be reliable
      proliferation indexes and useful prognostic markers in patients with muscle
      invasive urothelial bladder carcinomas.

PMID- 16112008
TI  - Galectin-3 expression in parathyroid carcinoma: immunohistochemical study of 26
      cases.
AB  - The diagnosis of parathyroid carcinoma (PC) is difficult and based on
      morphological features that are not totally reliable. Several molecular markers
      proved useful in the evaluation of PC, but their sensitivity, specificity, or
      both are rather low. With the aim of identifying a marker of malignancy in
      parathyroid tumors, we tested the expression of galectin-3 (Gal-3), a lectin
      expressed in several malignant tumors, including follicular carcinomas (but not
      adenomas) of the thyroid. Twenty-six PCs and 30 control parathyroid adenomas
      (PAs) were collected. The PCs had been diagnosed based on capsular/vascular
      invasion (26/26 cases), extraparathyroid infiltration (16), local recurrence (9),
      and distant metastases (6). All cases were immunohistochemically tested for Gal-3
      and for other markers claimed to be useful in the differential diagnosis of
      parathyroid neoplasms, namely, Ki67, p27, and bcl2. Gal-3 was expressed by 24 of
      the PC (92.3%), but only 1 PA (3.3%) (P < .001). All metastasizing PCs were Gal-3
      positive. As expected, the Ki67 proliferative index was higher in PCs (mean,
      6.7%) than in PAs (1.9%); p27 was down-regulated in 61.5% of PCs and only 33.3%
      of PAs, whereas bcl2 was strongly positive in most PAs and in 38.5% of PCs. In a
      suspected PC, the association of Gal-3 with Ki67 (using a cutoff of 6% for the
      proliferative activity) appeared the best marker combination (sensitivity 96.2%,
      specificity 90%), and the profile Gal-3-positive/Ki67 >6% was unique to PCs. We
      conclude that Gal-3 immunostaining is a valuable tool to support a diagnosis of
      PC in highly proliferating (Ki67 >6%) tumors affecting a single parathyroid
      gland.

PMID- 16112009
TI  - Survival of Mycobacterium tuberculosis organisms for 8 days in fresh lung tissue
      from an exhumed body.
AB  - Mycobacterium tuberculosis was isolated from the lung tissue of an 86-year-old
      unembalmed woman who was exhumed for an autopsy 8 days after her death. Autopsy
      prosectors should consider performing microbiological culture in all cases with a
      history or gross pathological findings suggestive of an infection even if the
      postmortem interval is extended. In addition, prosectors should still adhere to
      biosafety precautions for airborne pathogens, because a long postmortem interval
      does not necessarily provide assurance that these organisms are not viable.

PMID- 16112010
TI  - Positive troponin T without cardiac involvement in inclusion body myositis.
AB  - Cardiac troponin T (cTnT) is considered as a specific marker for acute myocardial
      infarction. Here, we present a case with elevated cTnT, determined by a third
      generation assay, without signs of a myocardial lesion. Routine investigation of
      a 66-year-old female patient with indolent B-cell lymphoma revealed increased
      serum levels of creatine kinase (CK), MB fraction of CK (CK-MB), and cTnT,
      although she did not complain of cardiac symptoms. Electrocardiographic
      monitoring, echocardiography, magnetic resonance computed angiography, and
      percutaneous coronary angiography excluded myocardial damage. However, the close
      follow-up showed a steady increase of CK-MB and cTnT levels and gradual
      development of weakness in both thighs. A biopsy of the right quadriceps muscle
      led to the diagnosis of inclusion body myositis. In contrast to cTnT, cardiac
      troponin I could not be detected retrospectively in any of her serum samples.
      These results demonstrate for the first time that cTnT is elevated in patients
      with inclusion body myositis.

PMID- 16112011
TI  - Subperitoneal placenta accreta succenturiate in the case of a successful near
      term extrauterine abdominal pregnancy.
AB  - Placenta from an extrauterine abdominal pregnancy was examined after a 37-week
      healthy infant gestation. The placenta, with its fetal surface down and maternal
      surface up, protruded from the pelvic area to peritoneal cavity in the wall of
      the amniotic sac containing fetus. The placenta was implanted under the thin
      subperitoneal layer of maternal tissue completely covered by peritoneal serosa
      and was formed by several small lobes connected by intramembranous placental
      vessels. Insertion of the trivascular umbilical cord was velamentous. Partially
      remodeled arteries infiltrated by intermediate trophoblast and frequent veins
      directly communicating with the placental intervillous space were identified in
      the subperitoneal maternal tissue. The term "placenta accreta" is appropriate in
      this case because villi in the basal plate implanted directly in the maternal
      subserosal connective tissue without intervening decidua.

PMID- 16112012
TI  - Intra-abdominal ovarian-type mucinous cystadenoma associated with fallopian tube
      like structure and aberrant epididymal tissue in a male patient.
AB  - Ovarian-type mucinous tumors may occasionally occur in the retroperitoneum,
      pancreas, and liver exclusively or almost exclusively in women. In men, only few
      cases of such neoplasms arising within or around the testis have been reported.
      We describe a unique case of an ovarian-type mucinous cystadenoma occurring in
      the peritoneal cavity of a 65-year-old male patient with secondary adrenocortical
      insufficiency and hypogonadism. There was a typical fallopian tube enclosed in
      the capsule of the tumor. Contiguous to that, accessory ectopic epididymal tissue
      was found. We have interpreted this case as the result of a minor disorder of
      embryonic development involving structures of both mullerian and wolffian origin.
      The disproportion of sexual hormones might have had a role in inducing intra
      abdominal mullerian remnants to give rise to the mucinous cystadenoma.

PMID- 16112013
TI  - I enjoyed the article about reserve cells.

PMID- 16112015
TI  - We would like to compliment Dr. Luigi et al.

PMID- 16112017
TI  - Effects of atrazine on metamorphosis, growth, laryngeal and gonadal development,
      aromatase activity, and sex steroid concentrations in Xenopus laevis.
AB  - African clawed frogs (Xenopus laevis) were exposed to one of eight nominal
      waterborne concentrations including 0, 0.1, 1.0, 10, or 25 microg/L atrazine,
      0.005% ethanol (EtOH), or 0.1mg/L estradiol (E2) or dihydrotestosterone (DHT)
      containing 0.005% EtOH. Frogs were exposed from 72 h posthatch until 2--3 months
      postmetamorphosis via a 3-day static renewal exposure regimen. Atrazine at
      concentrations between 0.1 and 25 microg/L did not significantly affect
      mortality, growth, gonad development, laryngeal muscle size, or aromatase
      activity in juvenile X. laevis. Male frogs exposed to 1.0 microg/L atrazine had
      lower E2 levels compared to controls, but this response was not consistent among
      other concentrations of atrazine. Male and female frogs exposed to DHT had larger
      laryngeal dilator muscle areas compared to controls. E2-exposed female frogs had
      decreased gonadal aromatase activity, and E2-exposed male frogs had statistically
      greater plasma concentrations of E2 compared to controls.

PMID- 16112018
TI  - Ecological risk assessment of contaminated soils through direct toxicity
      assessment.
AB  - A microcosm (MS-3) with a multispecies soil system is introduced as an
      experimental tool for direct toxicity assessment of contaminated soils. The
      capacity of MS-3 to determine soil ecotoxicity potential was evaluated using
      samples from three sites contaminated with organic and/or inorganic compounds.
      Soils were toxic to soil-dwelling organisms (earthworm, plants, and
      microorganisms) and to aquatic organisms (algae and RTG-2 cell fish). As
      expected, responses varied substantially among different soils and organisms. The
      application of this evaluation system provided complementary information to the
      chemical characterization. For soils containing metals the toxic response was
      lower than predicted from total metal concentrations. For hydrocarbons, the
      toxicity response agreed with estimated values. The induction of EROD activity
      suggested the presence of dioxin-like compounds, which had not been addressed in
      the chemical characterization. The proposed multispecies system affords the
      measurement of 11 endpoints covering three soil and three aquatic taxonomic
      groups, reproduces soil conditions and gradients, and appears as an excellent
      complementary tool to chemical analysis for characterization of contaminated
      sites.

PMID- 16112019
TI  - The ecological classification and assessment of soils.

PMID- 16112020
TI  - Foreword.

PMID- 16112021
TI  - Legislation and ecological quality assessment of soil: implementation of
      ecological indication systems in Europe.
AB  - Nationally and internationally there are an increasing number of legal
      initiatives to protect the ecological processes in soil. This article describes
      the legal situation concerning the protection of natural functions of soil in
      Europe (mainly The Netherlands (since 1987) and Germany (since 1998)). Examples
      of processes to be protected comprise the element cycles, the degradation of
      pollutants, and the conversion of organic matter. These processes are performed
      by organisms, and therefore, there is a growing consensus that protection of soil
      biodiversity is necessary for the survival of humans and the above-ground
      ecosystems. It is discussed that protection of soil ecosystems needs requires
      definitions and aims for the ecological quality of soil (as already provided for
      aquatic ecosystems). Taking into account that most soils are privately owned,
      legal initiatives are necessary to clarify responsibilities and to direct
      research toward the implementation of reproducible and standardized methods to
      determine the ecological quality of soil.

PMID- 16112022
TI  - HLAMatchmaker-based analysis of human monoclonal antibody reactivity demonstrates
      the importance of an additional contact site for specific recognition of triplet
      defined epitopes.
AB  - Five HLA-A3 reactive human monoclonal antibodies (mAbs) originating from a parous
      woman were screened against HLA-typed panels by means of complement-dependent
      lymphocytotoxicity, high-definition ELISA, and flow cytometry with single antigen
      beads. Antibody reactivity profiles were compared with triplet amino acid
      sequence polymorphisms identified by HLAMatchmaker, and a three-dimensional
      structural modeling program (Cn3D of the National Center for Biotechnology
      Information) was used to determine the topography of epitopes recognized by each
      mAb. These mAbs originated from a woman who during pregnancy developed antibodies
      to the paternal HLA-A3 antigen of her child. Each mAb was specific for one
      mismatched triplet on HLA-A3, and the reactivity patterns of these IgM-type mAbs
      were practically the same in lymphocytotoxicity and antigen-binding assays. One
      mAb was specific for 163dT, a unique triplet present only on A3. The other mAbs
      reacted with 62Qe, 142mI, or 144tKr; these triplets are present on different
      groups of HLA-A alleles, some of which, however, did not react. Topographic
      modeling of triplet-defined epitopes identified clusters of polymorphic surface
      residues that were shared between reactive alleles. These clusters may serve as
      primary contact sites for the specificity-determining complementarity-determining
      region (CDR) loops of antibody. The reactivity with these mAbs required also the
      presence of self-sequence elsewhere on the HLA molecular surface as a critical
      secondary contact site for antibody, likely through another CDR loop. For
      instance, the reactivity of the 62Qe-specific mAb required the presence of a
      glycine residue in position 56 and the reactivity of the 142mI-specific mAb
      required the presence of the GTLRG sequence in positions 79-83. Conversely, there
      were many other amino acid differences between the mAb-reactive alleles and HLA
      A3 that did not prevent antibody binding. For instance, the 62Qe-specific mAb
      reactive alleles had 35 and the 142mI-reactive alleles had 50 of such
      "permissive" residue differences. An HLAMatchmaker-based analysis of the
      reactivity of human mAbs will increase our understanding of the structural
      definition of HLA epitopes and their reactivity with alloantibodies.

PMID- 16112023
TI  - Human papillomavirus L1L2-E7 virus-like particles partially mature human
      dendritic cells and elicit E7-specific T-helper responses from patients with
      cervical intraepithelial neoplasia or cervical cancer in vitro.
AB  - We evaluated the ability of autologous dendritic cells (DC) pulsed with
      recombinant human papillomavirus 16 L1L2-E7 virus-like particles (VLPs) to
      stimulate E7-specific CD4+ T-cell responses from normal donors and patients with
      cervical intraepithelial neoplasia lesions or cervical carcinoma in vitro.
      Exposure to VLPs partially matured DCs, as evidenced by upregulated expression of
      costimulatory and major histocompatibility complex molecules and the reduced
      capacity of treated DCs to process exogenous antigens. However, VLP treatment
      failed to promote strong expression of the CD83 or CCR7 markers or to modulate
      interleukin-12p70 secretion, indicators of terminal DC maturation. Notably, both
      normal donor- and patient-derived DCs behaved similarly after exposure to VLPs. A
      single round of in vitro stimulation of CD4+ T cells with DCs exposed to L1L2-E7
      VLPs promoted specific anti-E7 responses in the majority of donors. In
      particular, DCs exposed to VLPs effectively stimulated type 1 biased E7-specific
      CD4+ T-cell responses in patients with premalignant cervical intraepithelial
      neoplasia I-III lesions, but type 2 or Treg biased responses in patients with
      cervical cancer. Given the high rate of CD4+ T-cell responses (14 [93%] of 15
      patients) against DC-L1L2-E7 VLP stimulation, this vaccine modality could serve
      as a foundation for developing a general treatment option for patients with human
      papillomavirus 16-associated malignancies.

PMID- 16112024
TI  - Characterization of CD28, CTLA4, and ICOS polymorphisms in three Brazilian ethnic
      groups.
AB  - Costimulatory molecules CD28, CTLA-4 (cytotoxic T-lymphocyte-associated antigen
      4), and ICOS (inducible costimulator) genes lie within the 300-kb chromosome
      region 2q33. CD28, CTLA-4, and ICOS have been described to be important
      regulators of T-cell activation. With the objective to study ethnic variations in
      allelic frequencies and linkage disequilibrium (LD) patterns, we genotyped CD28
      intron 3 (+17 T>C), CTLA4 promoter (-319 C>T), CTLA4 exon 1 (+49 A>G), and ICOS
      3' UTR (1564 T>C) polymorphisms in white (n = 103), mulatto (n = 97), and black
      (n = 79) Brazilian healthy individuals. No significant deviations from Hardy
      Weinberg equilibrium were found in any of the population samples. A higher
      frequency of CD28 +17 C allele was detected in white (27%) in comparison with
      mulatto (15%) and black (13%) (p = 0.005) populations. LD between CD28 +17 C and
      CTLA4 -319 T alleles was observed in whites (p < 0.0001), mulattos (p = 0.0001),
      and blacks (p = 0.0002).

PMID- 16112025
TI  - Persistence of herpes simplex virus type 2 VP16-specific CD4+ T cells.
AB  - Patients with genital herpes have frequent viral reactivations. The repeated
      antigenic rechallenges can modulate the CD4+ memory T-cell repertoires during the
      course of infection. In this study, the CD4+ T-cell responses against the herpes
      simplex virus type 2 (HSV-2) tegument protein VP16 were studied in two HSV-2
      infected subjects at two different time points that spanned a 5-year period.
      Although the VP16-specific T cells did exhibit variation of T-cell receptor Vbeta
      usages at the two time points, T cells that used identical Vbeta and CDR3
      junction sequences were also observed at the two time points. These experiments
      demonstrate that the CD4+ T cells that are directed against HSV-2 VP16 protein in
      chronically infected individuals are oligoclonal and that T cells of specific
      clonotypes can be maintained throughout the course of the disease.

PMID- 16112026
TI  - Extinction of the human leukocyte antigen homozygosity effect after two doses of
      the measles-mumps-rubella vaccine.
AB  - We have reported associations between human leukocyte antigen (HLA) homozygosity
      and low measles antibody levels after one dose of the measles, mumps, and rubella
      (MMR) vaccine. Here, we examined associations between HLA homozygosity and immune
      responses to MMR after two doses of vaccine. We examined associations between HLA
      homozygosity and measles antibody levels in a group of 178 children (cohort 1) as
      well as associations between homozygosity and antibody levels and
      lymphoproliferative responses to MMR in 346 children (cohort 2). In cohort 1, HLA
      homozygotes and heterozygotes had similar increases in measles antibody levels
      after a second dose of measles vaccine. In cohort 2, HLA homozygosity was not
      associated with measles immune measures after two doses of vaccine. Homozygosity
      at the DPB locus was associated with increased rubella antibody levels, and
      homozygosity at the class IA alleles was associated with lower mumps
      lymphoproliferative response. Homozygosity at increasing numbers of loci was also
      associated with lower mumps antibody levels and lymphoproliferative response.
      Therefore, two doses of the MMR vaccine appear to induce sufficient antibody
      levels and lymphoproliferative responses against measles and rubella, regardless
      of HLA homozygosity status. However, children who are HLA homozygous may be less
      protected against mumps compared with children who are heterozygous.

PMID- 16112027
TI  - Regulation of TNF-related apoptosis-inducing ligand-mediated death-signal pathway
      in human beta cells by Fas-associated death domain and nuclear factor kappaB.
AB  - Transfectants of human CM and NES2Y beta cell lines and primary islets
      transfected by FADD-DN (dominant-negative form of Fas-associated death domain), a
      mutant of FADD and/or a superrepressor of nuclear factor kappaB (NF-kappaB)
      (AdIkappaB(SA)2), were examined for their susceptibility to the TRAIL (TNF
      related apoptosis-inducing ligand)-induced death signal pathway, compared with
      controls, wild-type cells, and vector transfectants in caspase fluorescence,
      Western blot, electrophoretic mobility shift, apoptosis, and cytotoxicity assays.
      FADD-DN inhibited caspase-8 activation induced by TRAIL in the transfectants of
      CM and NES2Y cells. TRAIL-induced apoptosis and cytotoxicity to the FADD-DN
      transfectants were decreased in comparison to those responses in controls (CM, p
      < 0.01 and p < 0.01; NES2Y, p < 0.05, and p < 0.02, respectively). When CM,
      NES2Y, and primary islet cells were transfected by AdIkappaB(SA)2, TRAIL-induced
      IkappaB degradation and nuclear translocation of NF-kappaB p50/p65 were blocked.
      TRAIL-induced apoptosis and cytotoxicity to AdIkappaB(SA)2 transfectants of these
      cells were also reduced (CM, p < 0.02 and p < 0.02; NES2Y, p < 0.01 and p < 0.01,
      respectively, and islet p < 0.01 for cytotoxicity). Finally, cytotoxicity induced
      by TRAIL in CM and NES2Y cells transfected with both FADD-DN and AdIkappaB(SA)2
      was reduced, compared with that observed in these cells transfected with either
      FADD-DN alone or AdIkappaB(SA)2 alone, suggesting that FADD and NF-kappaB have
      synergistic proapoptotic regulatory effects on the susceptibility of beta cell
      lines and islet cells to TRAIL-induced destruction.

PMID- 16112028
TI  - Association of TAP1 and TAP2 gene polymorphisms with systemic sclerosis in Korean
      patients.
AB  - We sought to determine whether transporter associated with antigen processing
      (TAP) gene polymorphism is associated with susceptibility to systemic sclerosis
      (SSc). TAP1 and TAP2 gene polymorphisms were analyzed in 61 Korean patients with
      SSc and 100 ethnically matched healthy Koreans by polymerase chain reaction
      restriction fragment length polymorphism. Human leukocyte antigen (HLA)-DRB1
      genotyping data of the patients from our previous study was used for the
      assessment of independent role of TAP genes to SSc susceptibility. Patients were
      stratified according to anti-topoisomerase I (anti-topo I) antibody status and
      clinical subsets of diffuse and limited cutaneous SSc (dcSSc and lcSSc). TAP1 and
      TAP2 gene polymorphisms were associated with different subsets of SSc: TAP1*A/A
      genotype with anti-topo I-positive dcSSc (p = 0.01, p corrected = 0.04),
      TAP2*A1/C genotype with anti-topo I-positive lcSSc (p < 0.05), TAP2*Bky2 and *C
      alleles with anti-topo I-negative dcSSc (both p < 0.05), and TAP2*B/E genotype
      with anti-topo I-negative lcSSc (p = 0.004). Although TAP gene associations were
      generally weak, some associations (TAP2*A1/C, TAP2*C, and TAP2*B/E) with
      different subsets of SSc were independent of HLA-DR associations, revealing even
      stronger associations (TAP2*A1/C and TAP2*C) among individuals not possessing the
      risk HLA-DR alleles. These results suggest the possible role of TAP gene
      polymorphisms in the genetic susceptibility to SSc.

PMID- 16112029
TI  - Sensitivity to bee venom antigen phospholipase A2: association with specific HLA
      class I and class II alleles and haplotypes in beekeepers and allergic patients.
AB  - Bee venom hypersensitivity is a clinical entity of outstanding importance because
      bee stings are a leading cause of mortality worldwide. Individuals with immediate
      type bee venom hypersensitivity, beekeepers, and healthy controls were examined
      for HLA-DRB1, DQB1, and DQA1 alleles by sequence-specific oligonucleotide probe
      typing. Defined hypersensitivity to bee venom antigen phospholipase A2 (vbPLA2)
      is significantly associated with the presence of susceptible HLA class II
      alleles: DRB1*0101 (RR = 2.7, p < 3 x 10(-3)), DRB1*0103 (RR = 21.2, p < 7.5 x
      10(-11)), DQA1*0101 (RR = 1.2, p < 38.52 x 10(-10)), and DQB1*0501 (RR = 4, p <
      2.18 x 10(-10)). Some HLA class I alleles were also associated with risk to bee
      venom allergy: A*01 (RR = 2.4, p < 7.5 x 10(-4)), B*57 (RR = 35.1, p < 3.5 x 10(
      7)), and B*5901 (p < 3.5 x 10(-5)), but they are probably of secondary
      significance. Three- (DRB1*0103-DQA1*0101-DQB1*0501) (RR = 21.24, p < 7.5 x 10(
      11)) and five-loci (A*01-B*59-DRB1*0103-DQA1*0101-DQB1*0501) (p < 2.3 x 10(-6))
      extended haplotypes are also significantly carried by vbPLA2 allergic patients.
      When HLA allele frequencies from patients are compared with those from
      beekeepers, only HLA-DRB1*0103 (RR = 11.7, p < 8.5 x 10(-5)) and HLA-DQA1*0101 (p
      < 0.02) were significantly increased in the former. These observations emphasize
      the importance of the DRB1*0103-DQA1*0101-DQB1*0501 haplotype as a strong
      candidate for susceptibility to vbPLA2 hypersensitivity, at least in our region.

PMID- 16112030
TI  - Severe pulmonary sarcoidosis is strongly associated with the haplotype HLA
      DQB1*0602-DRB1*150101.
AB  - Sarcoidosis is a multiorgan granulomatous disease of unknown etiology. Several
      lines of evidence suggest a genetic predisposition and associations have been
      demonstrated with HLA antigens. HLA-DQB1 has been proposed as one of the
      candidate genes. To investigate the relationship between DQB1 and sarcoidosis at
      the allele level, we typed 149 Dutch Caucasian sarcoidosis patients for DQB1 by
      sequence-based typing as the ultimate technique to identify all DQB1 alleles.
      Phenotype frequencies were compared with controls. Both groups were also typed
      for HLA-A, -B, and -DRB1 at the low-resolution level. To decide on the possible
      linkage with DR, all DRB1*15-positive patients were subsequently sequence-based
      typed. Results showed a statistically significant increase of DQB1*0602 in
      sarcoidosis patients. The increase was also proven for DRB1*150101. Because of
      the high linkage disequilibrium between DRB1*1501 and DQB1*0602 in Caucasians, it
      could not be decided which one was the primary association. The increase was most
      pronounced in patients with severe pulmonary sarcoidosis indicated by
      radiographic stages II-IV. Although not statistically significant, DRB1*03 and
      DQB1*0201 were increased in radiographic stage I compared with II-IV. This study
      provides evidence that the combination DQB1*0602/DRB1*150101 is a strong positive
      marker for severe pulmonary sarcoidosis.

PMID- 16112031
TI  - Activating killer cell immunoglobulin-like receptor gene KIR2DS1 is associated
      with psoriatic arthritis.
AB  - Killer cell immunoglobulin-like receptor genotyping was performed on a cohort of
      American Caucasian patients with psoriasis to investigate any possible
      relationship between these chromosome 19 genes and autoimmune-linked disease.
      This patient cohort also contained a subgroup of patients who had been
      additionally diagnosed as positive for psoriatic arthritis (PsA). Because of the
      known association of human leucocyte antigen (HLA)-Cw*06 with psoriasis, the
      study concentrated on the five KIR genes that have HLA-C as their recognized
      ligand (i.e., KIR2DL1, -2DL2, -2DL3, -2DS1, and -2DS2). An increase in the
      frequency of the activating KIR2DS1 gene was detected in the PsA patients,
      compared with psoriasis patients negative for PsA and an unaffected American
      Caucasian control group.

PMID- 16112032
TI  - Hyper-IgE syndrome is not associated with defects in several candidate toll-like
      receptor pathway genes.
AB  - The genetic basis of hyper-IgE syndrome (HIES), also known as Job syndrome, a
      primary immunodeficiency associated with recurrent skin and pulmonary infections,
      is unknown. We hypothesized that HIES is due to a defect in the Toll-like
      receptor signaling pathway. We used a whole blood cytokine assay to compare
      inflammatory responses to stimulation with specific Toll-like receptor (TLR)
      pathway agonists in four individuals with HIES and nine healthy controls.
      Production of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL
      12 was not impaired in response to stimulation with lipopolysaccharide,
      peptidoglycan, zymosan, lipoteichoic acid, Staphylococcus aureus, Escherichia
      coli, or Streptococcus pneumoniae. Interferon (IFN)-gamma was reduced in HIES
      subjects in response to each of these stimuli. We sequenced several candidate
      genes from the TLR pathway in HIES individuals to determine whether any mutations
      were associated with this syndrome. No novel mutations or polymorphisms were
      found in the coding regions of TLR1, TLR2, TLR6, MyD88, or TRAF6. In summary,
      although HIES individuals had an IFN-gamma secretion defect, they also produced
      normal levels of several TLR-regulated proinflammatory cytokines. No unique
      mutations or polymorphisms were observed in several candidate genes from the TLR
      pathway. Our studies do not support a role for a defective TLR response in HIES
      individuals.

PMID- 16112033
TI  - C1858T functional variant of PTPN22 gene is not associated with celiac disease
      genetic predisposition.
AB  - Recent findings have demonstrated that the single nucleotide polymorphism 1858C-
      >T located at the P1 motif of the PTPN22 (protein tyrosine phosphatase
      nonreceptor 22) gene has functional relevance and is associated with a variety of
      autoimmune diseases. The aim of this study was to assess the role of the PTPN22
      1858C-->T polymorphism in the genetic predisposition to celiac disease (CD). We
      analyzed a case-control cohort composed by 534 patients with CD and 653 healthy
      controls and additionally a panel of 271 celiac families. The PTPN22 1858C-->T
      genotyping was performed by TaqMan 5' allelic discrimination assay. We did not
      observed any statistically significant deviation after comparing allele and
      genotypic frequencies of PTPN22 1858C-->T between patients with CD and controls.
      Accordingly, the familial analysis did not reach statistically significant
      deviation in the transmission of PTPN22 1858C-->T alleles to the affected
      offspring. Therefore, our data suggest that the PTPN22 1858 single nucleotide
      polymorphism has no, or only a negligible, effect on CD susceptibility in this
      Spanish population.

PMID- 16112034
TI  - CAPD-related peritonitis due to Salmonella enteritidis in a patient with SLE.
AB  - Patients with systemic lupus erythematosus are prone to various infections, often
      associated with high mortality. Salmonella species are a rare cause of continuous
      ambulatory peritoneal dialysis (CAPD) peritonitis, but patients with lupus are
      susceptible to infection caused by Salmonella species. A 47-year-old woman who
      had systemic lupus erythematosus with end-stage renal disease and was undergoing
      CAPD presented with fever, watery diarrhea, abdominal pain, and turbid dialysate
      effluent. The effluent culture yielded Salmonella enteritidis. Although she was
      administered antibiotics to which the organism was susceptible in vitro,
      peritonitis was not cured. Her clinical condition stabilized after removal of the
      Tenckhoff catheter and prolonged antibiotic use. In Salmonella-related CAPD
      peritonitis, early catheter removal may be necessary to achieve complete
      treatment.

PMID- 16112035
TI  - Development of lupus nephritis in a patient with human T-cell lymphotropic virus
      type I-associated myelopathy.
AB  - A 77-year-old Japanese man with a 14-year history of human T-cell lymphotropic
      virus type I-associated myelopathy developed pancytopenia, proteinuria, renal
      dysfunction, and hypocomplementemia. Antinuclear antibody and anti-double
      stranded DNA antibody test results were positive, and circulating immune
      complexes were detected. A renal biopsy showed diffuse and global
      mesangiocapillary proliferation with extensive subendothelial deposits.
      Immunofluorescence microscopy showed strong granular staining for immunoglobulins
      and complements in the mesangium and along capillary walls. Electron microscopy
      showed numerous mesangial and subendothelial electron-dense deposits. From these
      findings, systemic lupus erythematosus and diffuse global lupus nephritis were
      diagnosed. This is a rare case of a patient developing lupus nephritis during the
      long-term course of human T-cell lymphotropic virus type I-associated myelopathy.

PMID- 16112036
TI  - Systemic vasculitis: still a challenging disease.
AB  - The efficacy of current therapeutic regimens in patients with systemic vasculitis
      is high, at the expense of considerable treatment toxicity. Optimal therapy for
      patients with these potentially life-threatening diseases is still debated. Our
      increased understanding of the pathogenetic mechanisms of systemic vasculitis has
      led to the development of new therapeutic alternatives, with better potential
      specificity for both the inflammation and immunologic causes of vasculitis: new
      immunosuppressive drugs (mycophenolate), monoclonal antibody modulators of
      lymphocyte function (rituximab), and cytokine-directed therapies (infliximab and
      eternacept). The safety and efficacy of such agents increasingly are being
      investigated in patients with systemic vasculitis. Additionally, many randomized
      prospective clinical trials have been completed to determine the precise roles
      for more conventional treatments (cyclophosphamide, azathioprine, and plasma
      exchange), providing an expanding evidence base to guide therapy in these
      challenging diseases. There now is clear evidence that duration of
      cyclophosphamide therapy can be relatively short (3 months), long-term
      maintenance therapy is needed to avoid relapse (often azathioprine), and patients
      at relatively greater risk for relapse can be identified. We review the most
      recent data on the current management of systemic antineutrophil cytoplasmic
      antibody-associated vasculitis, with emphasis on strategies to improve long-term
      outcome and reduce treatment toxicity while minimizing the risk for relapse.

PMID- 16112037
TI  - Asymmetric dimethylarginine: a cardiovascular risk factor and a uremic toxin
      coming of age?
AB  - The idea that asymmetric dimethylarginine (ADMA) accumulation may be a
      cardiovascular risk factor in patients with end-stage renal disease was advanced
      by Vallance in 1992. During the last decade, the relationship between ADMA and
      adverse cardiovascular events, including death, in dialysis patients has been
      investigated thoroughly. Several studies have shown that, independently of other
      risk factors, ADMA is strongly associated with intima-media thickness of the
      carotid artery and left ventricular mass, particularly concentric left
      ventricular hypertrophy. Furthermore, cohort studies in both the general
      population and the dialysis population showed a strong and independent link
      between ADMA, all-cause mortality, and cardiovascular events. Circumstantial
      evidence indicates that norepinephrine and ADMA may be in the same causal pathway
      leading to cardiovascular complications in patients with end-stage renal disease.
      Several lines of evidence show that high ADMA levels may exert toxic effects in
      various cell types. High ADMA levels have been associated with alterations in the
      regulation of cerebral blood flow and neural function, with insulin resistance,
      thyroid dysfunction, and alterations in bone homeostasis, fertility, and erectile
      function. The clinical significance of decreasing plasma ADMA concentrations, if
      any, is unknown. Well-designed and carefully conducted studies are needed to
      further clarify the role of ADMA in the pathophysiological states of renal
      disease and explore possible treatment options to improve the prognosis of
      patients with elevated ADMA levels. ADMA may enable us to predict risk and follow
      up the course of renal diseases.

PMID- 16112038
TI  - Area socioeconomic status and progressive CKD: the Atherosclerosis Risk in
      Communities (ARIC) Study.
AB  - BACKGROUND: Individual-level socioeconomic status (SES) has been found to be
      associated inversely with progressive chronic kidney disease (CKD); the effect of
      area-level SES on progressive CKD is less known. We conducted a cohort study of
      12,856 Atherosclerosis Risk in Communities Study participants to examine the
      independent risk for progressive CKD associated with living in a low SES area.
      METHODS: Progressive CKD is defined as a creatinine level elevation of 0.4 mg/dL
      or greater (> or = 35 micromol/L) during a 9-year follow-up, hospitalization for
      CKD, or death. Area-level SES was characterized by using measures of income,
      wealth, education, and occupation for 1990 US Census block groups of residence.
      RESULTS: Age- and center-adjusted incidence rates (per 1,000 person-years) of
      progressive CKD by quartiles of area-level SES score showed increasing rates with
      decreasing SES for African-American women: quartile 1 (Q1; low) = 11.1, Q2 =
      10.5, Q3 = 6.4, and Q4 = 7.1 and white men: Q1 = 6.6, Q2 = 4.8, Q3 = 4.0, and Q4
      (high) = 3.5, but not for African-American men or white women. Cox proportional
      hazards models showed that living in the lowest versus the highest SES-area
      quartile was associated with a 60% greater risk for progressive CKD in white men
      after adjusting for age, center, baseline creatinine level, body mass index, and
      individual-level SES (hazard ratio, 1.6; 95% confidence interval, 1.0 to 2.5).
      This risk and trend persisted after adjusting for such potential mediators as
      health awareness, health care access, and behavioral and physiological factors.
      We found no significant association of progressive CKD risk and area SES in white
      women, African-American women, or African-American men after adjustment.
      CONCLUSION: For white men, living in a low SES area is independently associated
      with greater risk for progressive CKD. Future research is needed to examine this
      association, considering the disparate effects found by race/sex groups.

PMID- 16112039
TI  - Associations between retinal microvascular abnormalities and declining renal
      function in the elderly population: the Cardiovascular Health Study.
AB  - BACKGROUND: Microvascular abnormalities in the kidney are common histopathologic
      findings in individuals with chronic kidney disease or renal failure. These
      abnormalities may represent one manifestation of ongoing systemic microvascular
      damage. We hypothesized that retinal microvascular abnormalities, when present,
      would be associated with progressive renal dysfunction in elderly individuals.
      METHODS: The Cardiovascular Health Study (CHS) is a prospective, multicenter,
      cohort study initiated in 1989 designed to examine cardiovascular risk factors,
      morbidity, and mortality in elderly Americans. As part of an ancillary study, CHS
      participants underwent retinal photography in 1997 and 1998. Retinal
      microvascular abnormalities were assessed and graded by using standardized
      measures. Retinal microvascular abnormalities were defined as retinopathy (hard
      and soft exudates, hemorrhages, or microaneurysms) and/or retinal arteriolar
      abnormalities (arteriovenous nicking, focal arteriolar narrowing, or lowest
      quartile arteriole-venule ratio). Associations between these abnormalities and
      observed 4-year changes in serum creatinine levels and estimated glomerular
      filtration rates (eGFRs) from study years 5 to 9 (encompassing years 1994 to
      2001) were examined by using regression modeling. RESULTS: A total of 1,394 CHS
      participants had retinal and serum creatinine data. After adjustments for age,
      race, sex, weight, diabetes, hypertension, angiotensin-converting enzyme
      inhibitor use, and proteinuria, participants with retinopathy showed a
      significant increase in serum creatinine level and decline in eGFR compared with
      those without retinopathy during the 4-year study period (+0.24 mg/dL [+21
      micromol/L] versus -0.21 mg/dL [-19 micromol/L] and -0.48 mL/min/1.73 m2 [-0.01
      mL/s/1.73 m2] versus +1.74 mL/min/1.73 m2 [+0.03 mL/s/1.73 m2], respectively).
      Participants with retinopathy also were significantly more likely to have an
      observed significant deterioration in renal function, defined as a 0.3-mg/dL (27
      micromol/L) increase in serum creatinine level or 20% or greater decline in eGFR
      (odds ratio, 3.20; 95% confidence interval, 1.58 to 6.50; and odds ratio, 2.84;
      95% confidence interval, 1.56 to 5.16, respectively). These associations remained
      in separate stratified analyses of patients with and without diabetes. The
      presence of retinal arteriolar abnormalities was not associated with
      deteriorating renal function. CONCLUSION: Retinal microvascular abnormalities
      defined as retinopathy were significantly associated with renal function
      deterioration. The observed findings were independent of effects of any
      associated diabetes or hypertension. These findings suggest that systemic
      microvascular disease may be associated with progressive renal dysfunction in the
      elderly population.

PMID- 16112040
TI  - Identification of individuals with CKD from Medicare claims data: a validation
      study.
AB  - BACKGROUND: Medicare claims data might provide an efficient source for outcomes
      research in patients with chronic kidney disease (CKD). However, in the absence
      of laboratory data, one would need to identify patients with CKD from diagnosis
      codes associated with health care claims. The validity of this approach to
      identify patients with CKD has not been sufficiently studied. METHODS: From chart
      abstraction, we obtained the first serum creatinine measurement of 1,852 elderly
      Medicare beneficiaries upon hospitalization for myocardial infarction and
      estimated each patient's glomerular filtration rate. We then searched all
      Medicare claims of the preceding year for the presence of a diagnosis code for
      diabetic nephropathy, hypertensive nephropathy, chronic renal insufficiency,
      acute renal failure, and miscellaneous other renal diseases. Using the gold
      standard of an estimated glomerular filtration rate less than 60 mL/min/1.73 m2
      (<1.00 mL/s/1.73 m2) for definition of CKD, we calculated the sensitivity,
      specificity, and positive and negative predictive values for each of these
      diagnoses and combinations of these diagnoses. RESULTS: The sensitivity of
      individual diagnosis algorithms ranged from 2.7% for diabetic nephropathy to
      17.5% for miscellaneous. However, miscellaneous had a lower specificity (95.5%)
      than all other individual diagnosis algorithms (all > or =99%). Using
      combinations of these algorithms improved sensitivity up to 26.6%, but at the
      cost of lower specificity. Positive predictive values generally were high (85.7%
      to 97.5%), but negative predictive values were low (32.4% to 37.4%). CONCLUSION:
      High positive predictive values indicate that Medicare claims data can be used to
      accurately identify patients with CKD for study. However, the utility of such
      databases for comparison of patients with CKD versus lesser degrees of CKD is
      limited.

PMID- 16112041
TI  - Estimation of renal function in subjects with normal serum creatinine levels:
      influence of age and body mass index.
AB  - BACKGROUND: The Cockcroft-Gault (CG) and simplified Modification of Diet in Renal
      Disease (MDRD) formulas are the most widely used estimates of renal function. The
      influence of age and body mass index (BMI) on the performance of these equations
      was analyzed in 850 subjects with serum creatinine levels less than 1.5 mg/dL
      (<133 micromol/L). METHODS: Glomerular filtration rate (GFR) was measured as
      urinary clearance of continuously infused technetium Tc 99m-labeled diethylene
      triaminopentaacetic acid. Performance was assessed as bias, precision, and
      accuracy. RESULTS: In the total population, the CG and MDRD calculations based on
      enzymatic measurement of serum creatinine (which is constantly less than that
      obtained by using the alkaline picrate [Jaffe] method) significantly
      underestimated GFR by 4.9 and 12.4 mL/min/1.73 m2 (0.08 and 0.21 mL/s/1.73 m2),
      respectively. In patients 65 years and older, underestimation by means of the CG
      formula was enhanced, whereas that by means of the MDRD formula was blunted,
      compared with the group younger than 65 years (-11.3 versus -3.7 mL/min/1.73 m2 [
      0.19 versus -0.06 mL/s/1.73 m2] for CG and -3.7 versus -14.0 mL/min/1.73 m2 [
      0.06 versus -0.23 mL/s/1.73 m2] for MDRD). GFR was underestimated to a large
      extent by means of the MDRD equation irrespective of BMI. Conversely, the
      underestimation by means of the CG formula found in lean people (-13.0
      mL/min/1.73 m2 [-0.22 mL/s/1.73 m2]) was blunted in overweight people (BMI, 25 to
      30 kg/m2) and reversed to overestimation (+10.1 mL/min/1.73 m2 [+0.17 mL/s/1.73
      m2]) in obese subjects (BMI > 30 kg/m2). CONCLUSION: As suggested by estimations
      obtained using enzymatic serum creatinine measurement, the MDRD equation may be
      the estimation of choice in elderly patients, whereas the CG estimate is
      preferable in subjects younger than 65 years. Nevertheless, when obesity is
      present, no reliable estimation can be obtained by using the CG or MDRD formula.

PMID- 16112042
TI  - Performance of the Cockcroft-Gault and modification of diet in renal disease
      equations in estimating GFR in ill hospitalized patients.
AB  - BACKGROUND: Estimating glomerular filtration rate (GFR) in severely ill
      inpatients is clinically important for therapeutic interventions and prognosis,
      but notoriously difficult to do accurately. The Modification of Diet in Renal
      Disease (MDRD) equation and Cockcroft-Gault (CG) formula are widely used to
      estimate renal function in sick hospitalized patients; however, neither method
      has been validated in this setting. METHODS: Iodine 125-iothalamate clearances
      (iGFR) performed in 107 sick inpatients with renal dysfunction were compared with
      estimated GFRs (eGFRs) from the 6- and 4-variable MDRD (MDRD eGFR) and CG (CG
      eGFR) equations. RESULTS: Mean serum creatinine (SCr) level was 3.5 +/- 2.0 mg/dL
      (309 +/- 177 micromol/L), and mean iGFR was 17.1 +/- 17.9 mL/min/1.73 m2 (0.29 +/
      0.30 mL/s/1.73 m2). Six-variable MDRD eGFR was 22.5 +/- 17.4 mL/min/1.73 m2
      (0.38 +/- 0.29 mL/s/1.73 m2), 4-variable MDRD eGFR was 23.9 +/- 16.3 mL/min/1.73
      m2 (0.40 +/- 0.27 mL/s/1.73 m2), and CG eGFR was 26.0 +/- 17.1 mL/min/1.73 m2
      (0.43 +/- 0.29 mL/s/1.73 m2). Blood urea nitrogen (BUN)/SCr ratios greater than
      20 were seen in 58% of patients. Overall, the CG and MDRD equations overestimated
      iGFR, with poor agreement. Overestimation of at least 25% of measured iGFR was
      seen in 63%, 67%, and 70% of all inpatients when using the 6-variable MDRD, 4
      variable MDRD, and CG equations, respectively. Accuracy of eGFR within 50% of
      measured iGFR was 55% for the 6-variable MDRD equation, 49% for the 4-variable
      MDRD equation, and 40% for the CG formula. The performance of both methods
      deteriorated further in patients with a BUN/SCr ratio greater than 20.
      CONCLUSION: Estimation equations are performed poorly compared with iGFR and are
      not reliable measures of actual level of function in sick hospitalized patients,
      especially those with a high BUN/SCr ratio. Although use of the 6-variable MDRD
      equation provides a better estimation of GFR, it still is unsuitable for clinical
      application in this population.

PMID- 16112043
TI  - Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase
      ANCAs in crescentic glomerulonephritis.
AB  - BACKGROUND: In a substantial proportion of patients with crescentic
      glomerulonephritis (CGN), both anti-glomerular basement membrane (GBM) antibodies
      and antineutrophil cytoplasmic antibodies (ANCAs) with specificity for
      myeloperoxidase (MPO-ANCA) are detected. In the present study, we questioned
      whether histological and clinical features of patients with both ANCA and anti
      GBM antibodies differ from those of patients with either ANCA or anti-GBM alone.
      METHODS: We reviewed the Limburg renal biopsy registry (1978 to 2003; n = 1,373)
      for cases of CGN. The presence of linear fluorescence on renal biopsy and the
      presence of ANCA and/or anti-GBM antibodies were measured. Subsequently, we
      assessed patient characteristics and follow-up and compared histological findings
      among the different groups. RESULTS: We identified 46 MPO-ANCA-positive, 10
      double-positive, and 13 anti-GBM-positive patients. Mean ages were 63, 64, and 52
      years (P = 0.04), and serum creatinine levels were 5.0, 10.3, and 9.6 mg/dL (445,
      910, and 850 micromol/L), respectively (P = 0.01). Granulomatous periglomerular
      inflammation was found in either MPO-ANCA- or double-positive patients, but not
      in anti-GBM-positive patients with CGN without MPO-ANCAs. Patient survival among
      the 3 groups was different, although not statistically significant (log rank P =
      0.17, with 75%, 79%, and 100% alive at 1 year, respectively). Renal survival
      analysis showed significant differences among the 3 groups (P = 0.04, with 65%,
      10%, and 15% off dialysis therapy at 1 year, respectively). CONCLUSION: In
      patients with both anti-GBM antibodies and MPO-ANCAs, histological findings
      differ from those of patients with anti-GBM antibodies only. However, renal
      survival in these patients is not better than that in anti-GBM-positive patients
      and is worse compared with patients with MPO-ANCAs only.

PMID- 16112044
TI  - Nephrolithiasis and increased blood pressure among females with high body mass
      index.
AB  - BACKGROUND: We hypothesized that one reason for the heterogeneity in previously
      reported links between kidney stones and blood pressure (BP) was the differential
      effects of nephrolithiasis among subgroups of individuals. In particular, we
      hypothesized that the association between stone history and BP may vary with
      respect to sex and body size. METHODS: Data from the Third National Health and
      Nutrition Examination Survey were used to estimate the association between
      history of stone disease and odds of prior diagnosis of hypertension and mean
      difference in systolic BP, diastolic BP, and pulse pressure. Nine hundred
      nineteen persons with a history of stones and 19,120 persons without stones were
      available for analysis. RESULTS: In women, it was estimated that stone formers
      (SFs) experienced a 69% increase in odds of self-reported hypertension (95%
      confidence interval [CI], 1.33 to 2.17; P < 0.001). No significant difference was
      found in men. The estimated difference in mean systolic and diastolic BP
      comparing SFs with non-SFs increased with body mass index in both sexes, but was
      more pronounced in women. Mean systolic BPs in women SFs in quintiles 4 and 5 of
      body mass index were 7.62 mm Hg (95% CI, 1.04 to 14.2; P = 0.024) and 4.36 mm Hg
      (95% CI, 0.30 to 8.42; P = 0.036) greater than those in similar women non-SFs,
      respectively. CONCLUSION: Our findings not only support the link between kidney
      stone disease and BP, but also suggest that overweight women SFs may be at
      significantly increased risk for hypertension.

PMID- 16112045
TI  - Renal response after high-dose melphalan and stem cell transplantation is a
      favorable marker in patients with primary systemic amyloidosis.
AB  - BACKGROUND: Primary systemic (AL) amyloidosis is a rare plasma cell disorder
      characterized by soft-tissue deposition of monoclonal light chain fragments. High
      dose melphalan followed by autologous stem cell transplantation currently has
      become the treatment of choice. Favorable outcome is ensured with achievement of
      hematologic response, but little is known about organ response. This study was
      undertaken to determine the prognostic importance of renal response after high
      dose melphalan and stem cell transplantation. METHODS: All patients with AL
      amyloidosis who underwent autologous stem cell transplantation between 1996 and
      December 2002 were selected for study. Renal response is defined as a 50% or
      greater reduction in proteinuria with less than 25% decline in renal function.
      Exclusion criteria included pretransplantation dialysis therapy or dialysis
      dependence posttransplantation, treatment mortality, lack of proteinuria
      assessment posttransplantation, and baseline proteinuria with protein less than 1
      g/d. RESULTS: Of 105 patients, 47 were excluded for stated reasons. Renal
      response was achieved in 60.3% of evaluated patients. Proteinuria was reduced by
      greater than 90% in 37.9% and returned to normal in 15.5%. Median response time
      was 12 months. Renal response was associated with a greater increase in serum
      albumin level (P = 0.001), maintenance of renal function (P < 0.001), and better
      survival (P = 0.0003). Renal responders had better survival regardless of
      hematologic response (P = 0.01 to 0.05). CONCLUSION: Currently, high-dose
      melphalan followed by stem cell transplantation is the most effective treatment
      for AL amyloidosis for those who are eligible. Our data show that renal response
      after high-dose melphalan followed by stem cell transplantation is associated
      with improved survival. Renal response is an independent marker of treatment
      success and can be used in cases in which determination of hematologic response
      is difficult.

PMID- 16112046
TI  - Focal and segmental glomerulosclerosis and plasma cell proliferative disorders.
AB  - BACKGROUND: Focal and segmental glomerulosclerosis (FSGS) is a common
      histological finding in patients with proteinuria. The natural history of the
      condition varies, and although it may be responsive to therapy, FSGS is an
      important cause of end-stage renal disease. FSGS can be caused by a variety of
      conditions, but it has been reported rarely in association with a plasma cell
      disorder. METHODS: Mayo Clinic databases were queried and cross-referenced for
      FSGS and plasma cell disorders. The diagnoses were confirmed, and relevant
      clinical and laboratory data were abstracted. RESULTS: A cohort of 13 patients
      with "idiopathic" FSGS and a monoclonal plasma cell disorder were identified.
      Four patients had myeloma, and 9 patients had monoclonal gammopathy of
      undetermined significance. Patients treated for myeloma experienced improvement
      in their renal lesion, and the latter relapsed when the myeloma relapsed.
      CONCLUSION: We show that FSGS and plasma cell disorders are temporally and
      epidemiologically linked. Therapy for the underlying plasma cell disorder can
      lead to resolution of FSGS. The emerging molecular pathogenesis of both FSGS and
      myeloma also provides potential mechanisms that link the 2 conditions together.
      Thus, physicians must rule out a plasma cell proliferative disorder in patients
      with FSGS before concluding that the renal lesion is idiopathic. Moreover, FSGS
      may respond favorably after the underlying plasma cell disorder is controlled.

PMID- 16112047
TI  - Administration of intravenous iron sucrose as a 2-minute push to CKD patients: a
      prospective evaluation of 2,297 injections.
AB  - BACKGROUND: Intravenous iron supplementation is an integral part of the
      management of anemia in patients with chronic kidney disease. Traditionally, this
      has been administered as an infusion over 1 or more hours, which requires the use
      of intravenous fluids and administration tubing, along with extra demands on
      patient and nursing time. METHODS: We prospectively investigated the safety and
      practicality of administering iron sucrose, 200 mg, as a bolus injection over 2
      minutes in patients with chronic kidney disease. A total of 2,297 injections were
      administered to 657 patients. Any adverse events were recorded, including acute
      anaphylactoid reactions to the iron injection, along with the presence or absence
      of metallic taste and phlebitis, and these were classified as "serious" and
      "nonserious." RESULTS: The most common adverse event was a mild and transient
      metallic taste that occurred during 412 injections (17.9%); in no case was this
      of significant distress to the patient. Excluding this, 2,240 injections (97.5%)
      proceeded uneventfully, and no case of phlebitis was recorded. Adverse events
      other than metallic taste were recorded in association with 57 injections (2.5%).
      Seven of these were caused by an acute anaphylactoid reaction to the intravenous
      iron. All 7 acute reactions resolved completely within 30 minutes with no
      sequelae, and none required hospitalization. The remaining 50 adverse events
      consisted of pain during the injection (n = 31), pain after the injection with or
      without some bruising (n = 9), nausea/gastrointestinal symptoms (n = 3), lethargy
      (n = 4), and lightheadedness (n = 3). CONCLUSION: Administration of 200 mg of
      iron sucrose as an intravenous bolus injection over 2 minutes is a practical
      dosing regimen in patients with chronic kidney disease, resulting in considerable
      savings in time and cost.

PMID- 16112048
TI  - Diagnostic discordance for hepatitis C virus infection in hemodialysis patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is associated with an increase in
      proinflammatory cytokine levels. Similar changes are seen in maintenance
      hemodialysis patients with malnutrition-inflammation-cachexia syndrome (MICS),
      which is associated with poor clinical outcomes in this population. We
      hypothesized that HCV transcription-mediated amplification (TMA), a sensitive
      qualitative molecular test for HCV RNA, may identify maintenance hemodialysis
      patients with HCV infection not detected by means of antibody enzyme immunoassay
      (EIA), particularly in those with MICS. METHODS: We evaluated HCV status in 314
      maintenance hemodialysis patients by using HCV antibody EIA (version 2.0; Abbott
      Laboratories, Abbott Park, IL) and HCV TMA (Bayer Diagnostics Laboratories,
      Berkeley, CA). RESULTS: Twenty-five patients (8%) were EIA positive (EIA+)/TMA+;
      4 patients (1%), EIA+/TMA negative (TMA-), and 22 patients (7%), EIA-/TMA+. In
      the 47 TMA+ patients, the sensitivity of EIA for HCV infection was only 53%. TMA+
      patients had lower albumin levels and higher tumor necrosis factor alpha and
      serum glutamic oxaloacetic transaminase levels than TMA- patients. EIA+/TMA+
      patients were more likely than EIA-/TMA+ or EIA-/TMA- patients to have
      hypoalbuminemia and higher iron and transaminase levels. Of all TMA+ patients,
      EIA- patients were more likely to have diabetes, be on dialysis therapy longer,
      and have lower liver enzyme levels and higher proinflammatory cytokine levels,
      including tumor necrosis factor alpha and interleukin 6. CONCLUSION: Maintenance
      hemodialysis patients infected with HCV according to TMA have clinical features
      suggestive of MICS. In this population, HCV EIA appears to have a low sensitivity
      for the identification of HCV infection, which may be caused by the confounding
      effect of MICS or other demographic or clinical factors. These apparently false
      negative HCV antibody test results are seen in persons with a longer time on
      hemodialysis therapy, mirroring observations in other populations with serious
      progressive conditions, such as human immunodeficiency virus infection.

PMID- 16112049
TI  - Clinical and economic outcomes of Staphylococcus aureus septicemia in ESRD
      patients receiving hemodialysis.
AB  - BACKGROUND: Serious infections are a common problem in patients with end-stage
      renal disease (ESRD). The purpose of this study is to identify clinical and
      economic consequences of hospitalizations for septicemia caused by Staphylococcus
      aureus in hemodialysis patients with ESRD. METHODS: We conducted a retrospective
      analysis of data obtained from the US Renal Data System to determine lengths of
      stay and Medicare paid costs for index hospitalizations and episodes of care for
      patients with ESRD hospitalized with septicemia caused by S aureus. Factors
      associated with hospital length of stay and Medicare paid costs were examined in
      multivariate analysis. RESULTS: A total of 11,572 patient admissions with
      septicemia caused by S aureus were included; 20.7% of patients developed 1 or
      more complications. Average length of stay for the index admission was 13.0 days,
      and 11.8% of patients were readmitted within 12 weeks for care related to S
      aureus. Average Medicare cost for the index admission was 17,307 dollars. Average
      episodic cost of care, including the index hospitalization, outpatient visits,
      and readmissions related to S aureus during the subsequent 12 weeks, was 20,067
      dollars. S aureus--related complications were associated with greater episodic
      costs of care: no complications, 18,476 dollars; one complication, 25,804 dollars
      (P < 0.05 versus no complications); and 2 or more complications, 32,102 dollars
      (P < 0.05 versus no complications). In multivariate analysis, complications
      resulted in increased mean lengths of stay of 4 to 7 days, and complications were
      among the strongest predictors of total episodic costs. CONCLUSION: Patients with
      septicemia caused by S aureus had costly and lengthy hospitalizations, which
      frequently were associated with clinically and economically important
      complications, including hospital readmissions.

PMID- 16112050
TI  - The prevalence of ESRD treated with renal dialysis in France in 2003.
AB  - BACKGROUND: The prevalence of end-stage renal disease (ESRD) treated with renal
      dialysis is poorly known in France because there is no national registry of
      dialysis patients. The specific aims of this study are to determine the total
      number of patients treated with renal dialysis and their social, demographic, and
      clinical characteristics, as well as define the overall care they received.
      METHODS: We performed a cross-sectional descriptive study from June 2 to June 8,
      2003, in all renal dialysis units (including pediatric units) by including all
      patients residing in France with ESRD who were dialyzed during that week,
      irrespective of age or the treatment they received. We gathered sociodemographic
      (age, sex, place of residence, and occupation) and clinical data (year they
      entered dialysis therapy, initial renal disease, comorbidities, and associated
      handicaps) and information concerning their overall treatment plan (waiting list
      for kidney transplant, therapeutic regimen, and dialysis technique used).
      RESULTS: A total of 30,882 patients residing in France were treated with renal
      dialysis. The unadjusted prevalence of dialysis was 513.1 patients per million
      population (pmp); 498.2 pmp in metropolitan France and 1,035.7 pmp in the
      overseas territories. Clinical and sociodemographic characteristics of patients
      and their therapeutic regimens were different in metropolitan France and the
      overseas territories. CONCLUSION: This study constitutes the first comprehensive
      inventory of dialysis therapy in France, where the prevalence of ESRD is among
      the highest in the world.

PMID- 16112051
TI  - Frequency of elevated serum aluminum levels in adult dialysis patients.
AB  - BACKGROUND: Aluminum toxicity, a complication described in dialysis patients
      exposed to aluminum-containing phosphate binders or water used in dialysate
      preparations containing elevated levels of aluminum, can cause significant
      morbidity. Although physicians monitor patient aluminum levels, the frequency of
      abnormal aluminum levels has not been reported. METHODS: We retrospectively
      examined 1,410 measurements of serum aluminum in 207 dialysis patients at the
      Franklin Dialysis Center (FDC; Philadelphia, PA) from January 1, 2000, through
      April 3, 2003. We also surveyed serum aluminum levels from a nationwide dialysis
      provider (DaVita) to more than 43,000 patients. Local dialysis facilities were
      surveyed to determine the annual frequency of aluminum testing in their patients.
      RESULTS: Of 1,410 serum aluminum measurements performed at FDC, only 30 abnormal
      levels (2.1%) were found. DaVita measured approximately 117,000 aluminum levels
      annually during the last 3 years, of which 2.5% were abnormal. Frequencies of
      abnormal aluminum levels declined significantly each year at FDC and DaVita.
      CONCLUSION: The current frequency of abnormal aluminum levels in our dialysis
      facility and a national dialysis provider is extremely low and has significantly
      declined.

PMID- 16112052
TI  - Left ventricular hypertrophy in nondiabetic predialysis CKD.
AB  - BACKGROUND: Although left ventricular hypertrophy (LVH) is a strong predictor of
      mortality in patients with end-stage renal disease, few studies are available
      before the start of dialysis treatment. The purpose of this study is to evaluate
      the prevalence and clinical correlates of LVH in nondiabetic patients with
      chronic kidney disease (CKD) not yet undergoing renal replacement therapy.
      METHODS: We investigated 244 nondiabetic patients with CKD; 57 patients (42 men;
      age, 20 to 78 years) had stages 1 to 2 CKD and 187 patients (122 men; age, 18 to
      77 years) had stages 3 to 5 CKD. Fifty-two normotensive healthy subjects served
      as controls. Each patient had blood pressure (BP) measured by means of 24-hour
      ambulatory BP monitoring and left ventricular mass index (LVMi) assessed by means
      of M-mode echocardiography. Creatinine clearance was estimated by means of the
      Cockcroft-Gault formula, and hemoglobin, serum lipid, and intact parathyroid
      hormone concentrations and daily urinary protein excretion were assessed by using
      routine methods. RESULTS: In the overall group, prevalences of arterial
      hypertension and LVH were 66% and 74%, respectively. LVMi was 160 +/- 50 g/m2
      body surface area and associated directly with age (P = 0.0013), duration of
      arterial hypertension (P = 0.0075), 24-hour systolic BP (P = 0.0113), pulse
      pressure (P = 0.0003), daytime (P = 0.0206) and nighttime systolic BP (P =
      0.0059), and urinary protein excretion (P < 0.05) and inversely with creatinine
      clearance (P = 0.0103) and hemoglobin level (P = 0.0276). In patients with CKD
      stages 1 to 2 (LVH prevalence, 51%), age, duration of arterial hypertension,
      pulse pressure, and urinary protein excretion were significant predictors of LVMi
      (P < 0.00002) by using stepwise regression analysis, whereas in those with CKD
      stages 3 to 5 (LVH prevalence, 78%), pulse pressure emerged as the sole predictor
      of LVMi (P = 0.0011). CONCLUSION: The prevalence of LVH in nondiabetic
      predialysis patients with CKD is greater than previously reported, and there is
      evidence that LVH already is present in the early stages of renal disease.
      Arterial hypertension is associated with LVH in patients with CKD, and the strong
      relationship between elevated pulse pressure and LVH in those with more advanced
      CKD suggests that increased arterial stiffness might have a role for LVH well
      before the start of dialysis therapy.

PMID- 16112053
TI  - Interleukin-12 and -18 levels in peritoneal dialysate effluent correlate with the
      outcome of peritonitis in patients undergoing peritoneal dialysis: implications
      for the Type I/Type II T-cell immune response.
AB  - BACKGROUND: We previously showed that a positive impact of peritoneal defense
      response on the outcome of peritoneal dialysis (PD)-related peritonitis is
      characterized by an increased pattern of peritoneal CD4/CD8 T-cell ratio with a
      predominant CD4(+)-T helper subtype 1 phenotype. To further explore longitudinal
      changes in peritoneal immunity during PD-related peritonitis, we examined the
      production of interleukin 12 (IL-12), IL-18, and interferon gamma (IFN-gamma) in
      peritoneal dialysate effluent (PDE) and kinetic expression of the transcription
      factors T box expressed in T cells (T-bet) and guanine adenine thymine adenine
      (GATA) binding protein 3 (GATA-3) in peritoneal T cells during peritonitis.
      Correlations between these observations and responses to antibiotics were
      analyzed. METHODS: IL-12, IL-18, and IFN-gamma protein and IFN-gamma, T-bet, and
      GATA-3 messenger RNA (mRNA) were measured in PDE during various phases of
      peritonitis in 40 patients undergoing PD. Patients were divided into 2 groups
      according to whether they had a rapid versus delayed response to antibiotic
      treatment. RESULTS: In the early phase of peritonitis, IL-12, IL-18, and IFN
      gamma levels in PDE were significantly greater in the rapid-response group (P <
      0.05). Changes in peritoneal IL-12 and IL-18 levels preceded changes in IFN-gamma
      levels. The kinetics of IFN-gamma, T-bet, and GATA-3 mRNA expression in
      peritoneal T cells, measured by means of real-time polymerase chain reaction,
      differed between the 2 groups. In the rapid-response group, IFN-gamma and T-bet
      mRNA expression increased, whereas that of GATA-3 decreased over time. Results
      were opposite in the delayed-response group, with IFN-gamma and T-bet levels
      decreasing and GATA-3 levels increasing over time. CONCLUSION: These data suggest
      that local IL-12 and IL-18 production is part of a protective early immune
      response to PD-related peritonitis. High IL-12 and IL-18 levels in PDE during the
      early phase of peritonitis correlated with a predominant type 1 immune response
      and favorable outcome.

PMID- 16112054
TI  - Intolerance syndrome in failed renal allografts: incidence and efficacy of
      percutaneous embolization.
AB  - BACKGROUND: Immunologic intolerance to a failed renal allograft left in situ is
      referred to as graft intolerance syndrome, the incidence and predictors of which
      are unknown. Treatment by transcatheter vascular embolization has been reported
      to be less invasive than transplantectomy. The incidence of graft intolerance
      syndrome and results of transcatheter vascular embolization as a first
      therapeutic approach were studied. METHODS: A retrospective study of 149
      transplant recipients who returned to dialysis therapy between June 1989 and
      December 2001 was performed. After immunosuppression withdrawal, a diagnosis of
      graft intolerance syndrome was made based on clinical criteria and confirmed by
      the persistence of renal perfusion under imaging procedures. Potential
      immunologic predictors were analyzed. RESULTS: Of 149 patients with failed renal
      allografts, 55 patients (37%) developed graft intolerance syndrome during follow
      up (27.5 +/- 34.5 months; range, 1 to 173 months). Manifestations of graft
      intolerance syndrome were fever (88%), flu-like symptoms (33%), hematuria (39%),
      local pain (53%), and increased graft size (51%). Most episodes of graft
      intolerance syndrome appeared within 6 months (virtually all presented within 24
      months after graft failure). None of the immunologic variables studied showed an
      influence on graft intolerance syndrome. Transcatheter vascular embolization was
      performed in 48 patients and was successful in 31 patients (65%). A second
      embolization was necessary in 8 patients. No deaths or severe complications were
      observed. Eleven patients (22%) underwent transplantectomy because of persistent
      graft intolerance syndrome (n = 8) or graft infection (n = 3). CONCLUSION: Graft
      intolerance syndrome is common in patients with failed renal allografts left in
      situ, especially within the first year of returning to dialysis therapy. Our data
      support transcatheter vascular embolization as first-line therapy for patients
      with symptomatic failed renal allografts, although 1 in 4 patients will require
      transplantectomy.

PMID- 16112055
TI  - Alloimmune response against donor glutathione S-transferase T1 antigen in renal
      transplant recipients.
AB  - BACKGROUND: The long-term outcome of kidney transplantation could be influenced
      by the appearance of antibodies against donor-specific antigens. Glutathione S
      transferase T1 (GSTT1) is a protein preferentially expressed in liver and kidney
      cells. Deletion of the GSTT1 gene results in a complete lack of protein
      expression, which occurs in 20% of the white population. GSTT1 donor-recipient
      mismatch has been deleterious in liver transplantation. The purpose of this study
      is to examine immunologic and clinical consequences of a GSTT1 donor-recipient
      mismatch in kidney transplantation. METHODS: The presence of anti-GSTT1
      antibodies was studied retrospectively in sera from 135 patients who underwent
      transplantation before 1995. Samples from 89 patients who received a GSTT1
      positive kidney graft between December 1998 and May 2001 were collected
      prospectively. GSTT1 genotypes and anti-GSTT1 antibodies were studied by using
      standard methods. RESULTS: Seven patients, all with the null genotype, produced
      anti-GSTT1 antibodies. No transplant recipient with a positive genotype produced
      these antibodies. Six of 7 patients with antibodies also were positive for
      hepatitis C virus. Clinical outcomes of these patients did not differ from those
      of the entire group. CONCLUSION: After kidney transplantation, some patients with
      the null GSTT1 genotype who received a GSTT1-positive graft developed an immune
      response, with production of anti-GSTT1 antibodies. The presence of these
      antibodies did not seem to produce functional impairment in the graft. Hepatitis
      C virus seems to have a prominent role in this particular allograft immune
      response.

PMID- 16112056
TI  - Renal leiomyoma associated with Epstein-Barr virus in a pediatric transplant
      patient.
AB  - Renal leiomyoma is a rare smooth muscle tumor of the kidney. An association
      between Epstein-Barr virus and smooth muscle tumors in immunocompromised patients
      recently has been recognized. We describe a pediatric renal transplant patient
      who developed an Epstein-Barr virus-associated renal leiomyoma in his transplant
      kidney 5 years posttransplantation. Possible factors involved in the tumor
      pathogenesis in our patient are discussed, including immunosuppression, growth
      hormone therapy, and Epstein-Barr virus induction.

PMID- 16112057
TI  - Disorders of sodium and water.

PMID- 16112058
TI  - Diabetic woman with massive proteinuria and acute renal failure.

PMID- 16112059
TI  - Glucose metabolism in early renal failure.

PMID- 16112061
TI  - C-reactive protein: "cutoff" point and clinical applicability.

PMID- 16112064
TI  - Sodium depletion and hemoconcentration: overlooked complications in patients with
      anorexia nervosa?

PMID- 16112065
TI  - Mass spectrometric analysis of histone posttranslational modifications.
AB  - The uses of tandem and Fourier transform mass spectrometric methodologies for
      assignment of the posttranslational sites and occupancies of histones and their
      isoforms is described employing several illustrative examples. A comparison of
      information that can be obtained from intact protein sequencing and proteolytic
      digestion is presented.

PMID- 16112068
TI  - What we know about offenders who drive under the influence: analysis of court
      case file reviews.
AB  - This paper presents findings from a quantitative study about alcohol-impaired
      drivers in Utah. The University of Utah's Social Research Institute conducted a
      retrospective case file evaluation about the adjudication and sanctioning phases
      associated with driving under the influence (DUI) to determine Utah's response to
      DUI crime from arrest forward. Although Utah driver's license and court systems
      are on the cutting edge of dealing with DUI offenders, we found a variety of
      limitations for analysis due to data collection and entry. Therefore, it is
      difficult to develop a thorough understanding about the process of dealing with
      DUI offenders and the effectiveness of court actions and treatments. The purpose
      of this paper is to provide recommendations about how to ensure more accurate
      data collection about impaired drivers.

PMID- 16112069
TI  - Perceived susceptibility to and perceived causes of road traffic injuries in an
      urban and rural area of Tanzania.
AB  - The aim of the study was to investigate social and behavioral correlates of
      perceived vulnerability to traffic injuries in an urban and rural setting in
      Tanzania. In 2002, a sample of 494 adults aged 15 years and above participated in
      household interviews in Dar es Salaam (urban) and Hai District (rural). The study
      was part of a population-based survey that collected self-report data on non
      fatal injuries. In Dar es Salaam 75 and 82% of males and females, respectively,
      perceived it as likely that they would experience a traffic injury in general.
      The corresponding figures in Hai were 63 and 64%. Men rated their road traffic
      vulnerability similarly to women (OR=0.8, 95% CI 0.5-1.3). Factors associated
      with high perceived vulnerability as a pedestrian or being injured by a bicycle
      were amount of road safety information received from health workers and friends,
      having caused a car to swerve and having crossed a road while talking.
      Respondents perceived driver recklessness and driver drunkenness as the leading
      causes of traffic injuries in both areas. Differences were found between the
      urban and rural setting with respect to perceived risk for traffic injury. The
      implications of these findings in the context of traffic injury prevention are
      discussed.

PMID- 16112070
TI  - The impact of driver education on self-reported collisions among young drivers
      with a graduated license.
AB  - In this study, we assess the impact of driver education on the risk of collisions
      in a Graduated Licensing System (GLS). Ontario's GLS requires all new drivers to
      successfully pass through two stages of graduated license (referred to as G1 and
      G2, respectively) before full licensure is granted. Surveys of driving behaviour
      and related factors were administered to Grades 11 and 12 students with a
      graduated license in seven Ontario schools in 1996 and 1998. A total of 1533
      students completed the survey in 2 years. Multivariate logistic regression
      analysis revealed a significantly lower odds of self-reported collision
      involvement among G1 license holders with driver education (OR: 0.31, 95% CI:
      0.12-0.83). No significant effects were observed for G2 license holders. Other
      significant predictors of collisions include sex of driver, months of licensure
      and kilometers driven for G2 license holders. These results suggest that the
      impact of driver education may be dependent on the stage of driver learning in
      which it occurs.

PMID- 16112071
TI  - A double-blind field trial on the effects of artemether on Schistosoma japonicum
      infection in a highly endemic focus in southern China.
AB  - To further strengthen the evidence-base of artemether for the control of
      schistosomiasis japonica, a randomised controlled trial was carried out in the
      Poyang Lake region, a highly endemic area in southern China. A total of 783
      individuals, aged 6-60 years, were enrolled. They were first given a single oral
      dose of praziquantel (50 mg/kg). Then, they were randomly assigned oral
      artemether (6 mg/kg) or placebo, administered once every 2 weeks for 9-11 doses,
      covering the entire transmission season for Schistosoma japonicum in 2004. Stool
      examination 1 month after the final dosing revealed eggs of S. japonicum in 3/373
      (0.8%) of the artemether recipients and 56/361 (15.0%) in placebo recipients
      (chi2=53.69, P<0.001). Compared to the baseline, the geometric mean intensity of
      S. japonicum infection had decreased by 96.1% in the artemether group, and
      increased by 50.8% in the placebo group. No acute cases of schistosomiasis
      japonica were observed in the artemether group, whereas three such cases were
      reported from the placebo group. Compliance with regard to multi-doses of
      artemether and placebo was 84.9, and 77.9%, respectively. This study confirms
      that repeated oral artemether produces no drug-related adverse effects,
      significantly reduces incidence and intensity of patent S. japonicum infection
      and results in high compliance. Hence it can be used as an additional tool for
      the control of schistosomiasis japonica in the lake regions of China.

PMID- 16112072
TI  - Development of antischistosomal drugs in China, with particular consideration to
      praziquantel and the artemisinins.
AB  - Remarkable achievements have been made in the control of schistosomiasis in
      China, with chemotherapy playing a seminal role. From the early 1950s through the
      early 1980s, Chinese scientists made considerable progress in discovery and
      development of compounds with antischistosomal properties, including antimonials,
      non-antimonials and various effective principles stemming from traditional herbs.
      However, only few compounds entered clinical testing, while others were abandoned
      mainly due to their toxicity and poor efficacy. The advent of praziquantel in the
      1970s changed the landscape of research and development of drugs for treatment
      and morbidity control of schistosomiasis. The main Chinese contributions to
      enhance the understanding of the antischistosomal drug praziquantel are reviewed
      here, including issues of metabolism, antibody-dependency, host immune factors,
      stage-specific susceptibility and resistance. Over the past 25 years, researchers
      from China successfully developed artemether and artesunate, two derivatives from
      the antimalarial artemisinin, as promising drugs against Schistosoma japonicum.
      Laboratory investigations showed that the artemisinins display their highest
      activity against the juvenile stages of the parasite. These findings were
      consistently confirmed in randomised controlled trials; repeated oral
      administration of artemether or artesunate was safe and efficacious in the
      prevention of patent S. japonicum infections. The key findings are reviewed here,
      and emphasis is placed on how it stimulated research outside of China on other
      human schistosome species.

PMID- 16112073
TI  - Effects of neem limonoids on the malaria vector Anopheles stephensi Liston
      (Diptera: Culicidae).
AB  - The effects of the neem (Azadirachta indica A. Juss) limonoids azadirachtin,
      salannin, deacetylgedunin, gedunin, 17-hydroxyazadiradione and deacetylnimbin on
      Anopheles stephensi Liston (Diptera: Culicidae) were investigated. In exploring
      advantages of pure neem limonoids, we studied the larvicidal, pupicidal,
      adulticidal and antiovipositional activity of neem limonoids. Azadirachtin,
      salannin and deacetylgedunin showed high bioactivity at all doses, while the rest
      of the neem limonoids were less active, and were only biologically active at high
      doses. Azadirachtin was the most potent in all experiments and produced almost
      100% larval mortality at 1 ppm concentration. In general, first to third larval
      instars were more susceptible to the neem limonoids. Neem products may have
      benefits in mosquito control programs.

PMID- 16112074
TI  - Distinct characteristics of Ca(2+)-induced depolarization of isolated brain and
      liver mitochondria.
AB  - Ca(2+)-induced mitochondrial depolarization was studied in single isolated rat
      brain and liver mitochondria. Digital imaging techniques and rhodamine 123 were
      used for mitochondrial membrane potential measurements. Low Ca(2+) concentrations
      (about 30--100 nM) initiated oscillations of the membrane potential followed by
      complete depolarization in brain mitochondria. In contrast, liver mitochondria
      were less sensitive to Ca(2+); 20 microm Ca(2+) was required to depolarize liver
      mitochondria. Ca(2+) did not initiate oscillatory depolarizations in liver
      mitochondria, where each individual mitochondrion depolarized abruptly and
      irreversibly. Adenine nucleotides dramatically reduced the oscillatory
      depolarization in brain mitochondria and delayed the onset of the depolarization
      in liver mitochondria. In both type of mitochondria, the stabilizing effect of
      adenine nucleotides completely abolished by an inhibition of adenine nucleotide
      translocator function with carboxyatractyloside, but was not sensitive to
      bongkrekic acid. Inhibitors of mitochondrial permeability transition cyclosporine
      A and bongkrekic acid also delayed Ca(2+)-depolarization. We hypothesize that the
      oscillatory depolarization in brain mitochondria is associated with the transient
      conformational change of the adenine nucleotide translocator from a specific
      transporter to a non-specific pore, whereas the non-oscillatory depolarization in
      liver mitochondria is caused by the irreversible opening of the pore.

PMID- 16112075
TI  - Energy coupling to nitrate uptake into the denitrifying cells of Paracoccus
      denitrificans.
AB  - This study deals with the effects of the agents that dissipate the individual
      components of the proton motive force (short-chain fatty acids, nigericin, and
      valinomycin) upon the methyl viologen-coupled nitrate reductase activity in
      intact cells. Substitution of butyrate or acetate for chloride in Tris-buffered
      assay media resulted in a marked inhibition at pH 7. In a Tris--chloride buffer
      of neutral pH, the reaction was almost fully inhibitable by nigericin.
      Alkalinisation increased the IC(50) value for nigericin and decreased the maximal
      inhibition attained. Both types of inhibitions could be reversed by the
      permeabilisation of cells or by the addition of nitrite, and that caused by
      nigericin disappeared at high extracellular concentrations of potassium. These
      data indicate that nitrate transport step relies heavily on the pH gradient at
      neutral pH. Since the affinity of cells for nitrate was strongly diminished by
      imposing an inside-positive potassium (or lithium) diffusion potential at
      alkaline external pH, a potential dependent step may be of significance in the
      transporter cycle under these conditions. Experiments with sodium-depleted media
      provided no hints for Na(+) as a possible H(+) substitute.

PMID- 16112076
TI  - The bacterial-like lactate shuttle components from heterotrophic Euglena
      gracilis.
AB  - The structural and kinetic analyses of the components of the lactate shuttle from
      heterotrophic Euglena gracilis were carried out. Mitochondrial membrane-bound,
      NAD(+)-independent d-lactate dehydrogenase (d-iLDH) was purified by
      solubilization with CHAPS and heat treatment. The active enzyme was a 62-kDa
      monomer containing non-covalently bound FAD as cofactor. d-iLDH was specific for
      d-lactate and it was able to reduce quinones of different redox potential values.
      Oxalate and l-lactate were mixed-type inhibitors of d-iLDH. Mitochondrial l-iLDH
      also catalyzed the reduction of quinones, but it was inactivated during the
      extraction with detergents. Both l-iLDH and d-iLDH were inhibited by the specific
      flavoprotein-inhibitor diphenyleneiodonium, suggesting that l-iLDH was also a
      flavoprotein. Affinity chromatography revealed that the E. gracilis cytosolic
      fraction contained two types of NAD(+)-dependent LDH specific for the generation
      of d- and l-lactate (d-nLDH and l-nLDH, respectively). These two enzymes were
      tetramers of 126-132 kDa and showed an ordered bi-bi kinetic mechanism. Kinetic
      properties were different in both enzymes. Pyruvate reduction by d-nLDH was
      inhibited by its two products; the d-lactate oxidation was 40-fold lower than
      forward reaction. l-lactate oxidation by l-nLDH was not detected, whereas
      pyruvate reduction was activated by fructose-1, 6-bisphosphate, K(+) or NH(4)(+).
      Interestingly, membrane-bound l- and d-lactate dehydrogenases with quinone
      reductase activity have been only detected in bacteria, whereas the activity of
      soluble d-nLDH has been identified in bacteria and some yeast. Also, FBP
      activated l-nLDH has been found solely in lactic bacteria. Based on their similar
      kinetic and structural characteristics, a possible common origin among bacterial
      and E. gracilis lactic dehydrogenase enzymes is discussed.

PMID- 16112077
TI  - The outcome of group parent training for families of children with attention
      deficit hyperactivity disorder and defiant/aggressive behavior.
AB  - The effects of group parent training on parent behavior, and on the behavior of
      45 children with attention-deficit hyperactivity disorder and defiant aggressive
      behavior, were evaluated with a pre-post design. Parent training included
      didactics on the features and etiology of ADHD and its relationship to
      defiant/aggressive behavior, as well as parenting skills that adhered to
      parameters established in the Behavior Management Flow Chart (BMFC). The logic
      that guided the construction of the program and the unique aspects in the form
      and content of the parent training are identified. Outcome data show that
      training reduced childrens' hyperactive, defiant, and aggressive behavior,
      improved parenting behavior, and reduced parent stress. These data are comparable
      to previous outcome research evaluating the efficacy of parent training with the
      BMFC. The advantages of programs that are efficacious in group settings are
      discussed.

PMID- 16112078
TI  - Some distinctions between flavin-containing and cytochrome P450 monooxygenases.
AB  - This minireview summarizes information concerning the differences and
      similarities of the human flavin-containing- (FMO, E.C. 1.14.13.8) and the
      cytochrome P450-monooxygenases (CYP, E.C. 1.14.14.1). Human FMO oxygenates soft
      nucleophiles. CYP mainly catalyzes C-H abstraction but also oxidizes nitrogen-
      and sulfur-containing compounds. Both FMO and CYP generally convert lipophilic
      compounds into more hydrophilic metabolites. The mechanism by which each
      monooxygenase operates is quite distinct. Sometimes, CYP or FMO bioactivate
      chemicals to reactive metabolites but to date, drug toxicity thus far observed in
      the clinic is mainly the result of CYP-dependent oxidation. Both FMO and CYP
      possess genetic variability that may contribute to inter-individual variability
      observed for drug metabolism. In contrast to CYP, FMO is not induced or readily
      inhibited and potential adverse drug-drug interactions are minimized for drugs
      prominently metabolized by FMO. These properties may provide advantages in drug
      design, and by incorporating FMO detoxication pathways into drug candidates, more
      drug-like materials may emerge.

PMID- 16112079
TI  - Double dioxygenation by mouse 8S-lipoxygenase: specific formation of a potent
      peroxisome proliferator-activated receptor alpha agonist.
AB  - Mouse 8S-lipoxygenase (8-LOX) metabolizes arachidonic acid (AA) specifically to
      8S-hydroperoxyeicosatetraenoic acid (8S-HPETE), which will be readily reduced
      under physiological circumstances to 8S-hydroxyeicosatetraenoic acid (8S-HETE), a
      natural agonist of peroxisome proliferator-activated receptor alpha (PPAR alpha).
      Here, we investigated whether 8-LOX could further oxygenate AA and whether the
      products could activate PPARs. The purified recombinant 8-LOX converted AA
      exclusively to 8S-HPETE and then to (8S,15S)-dihydroperoxy-5Z,9E,11Z,13E
      eicosatetraenoic acid (8S,15S-diHPETE). The kcat/Km values for 8S-HPETE and AA
      were 3.3x10(3) and 2.7x10(4) M(-1) s(-1), respectively. 8-LOX also dioxygenated
      8S-HETE and 15S-H(P)ETE specifically to the corresponding 8S,15S-disubstituted
      derivatives. By contrast, 15-LOX-2, a human homologue of 8-LOX, produced 8S,15S
      diH(P)ETE from 8S-H(P)ETE but not from AA nor 15S-H(P)ETE. 8S,15S-diHETE
      activated PPAR alpha more strongly than 8S-HETE did. The present results suggest
      that 8S,15S-diH(P)ETE as well as 8S-H(P)ETE would contribute to the physiological
      function of 8-LOX and also that 8-LOX can function as a potential 15-LOX.

PMID- 16112080
TI  - Linkage exclusion analysis of two important chromosomal regions for height.
AB  - Adult height (stature), as an important parameter of human physical development,
      has been studied in many populations. Recently, we reported a whole genome scan
      of height on a sample of 630 Caucasian subjects from 53 human pedigrees. Two
      chromosome regions, 6q24-25 and 7q31.3-36, achieved low linkage signals
      (multipoint LOD score 0.5), but gained significant results in the linkage studies
      of height by other groups. In addition, the region 6q24-25 harbors the ER-alpha
      gene, an important candidate gene for linear growth. To resolve the controversies
      over these two regions for height, linkage exclusion analyses were performed in
      an extended sample of 79 pedigrees with 1816 subjects, which include the 53
      pedigrees containing 630 subjects for our previous whole genome study and
      additional 128 new subjects, and 26 new pedigrees containing 1058 subjects. The
      two regions, 6q24-25 and 7q31.3-36, were excluded at a relative effect size of
      10% or greater (p value < 0.0005) and 5% or greater (p value < 0.0018),
      respectively. Our results suggest that the two regions may not contribute
      substantially to height variation in our Caucasian population.

PMID- 16112081
TI  - GrinchGEF--a novel Rho-specific guanine nucleotide exchange factor.
AB  - RhoGTPases, which are activated by specific guanine nucleotide exchange factors
      (GEFs), play pivotal roles in several cellular functions. We identified a new
      RhoGEF (GrinchGEF) containing the typical Dbl homology domain, a putative WD40
      like domain, and two predicted transmembrane helices. In contrast to most other
      RhoGEFs, it exhibits no sequence similarities to known pleckstrin homology
      domains. GrinchGEF mRNA was highly abundant in skeletal muscle and pancreas.
      Despite the predicted transmembrane domains, subcellular localization studies
      revealed a cytosolic distribution. In vitro, GrinchGEF induced the GDP/GTP
      exchange at RhoA, but not at Rac1 or Cdc42. In intact cells, GrinchGEF induced
      specifically Rho activation and enhanced RhoA-C-specific downstream effects.

PMID- 16112082
TI  - Molecular cloning and functional analysis of a novel Cx43 partner protein CIP150.
AB  - We identified and cloned a novel gene encoding a partner protein, CIP150, of
      connexin 43 (Cx43). CIP150 associates with Cx43 through its carboxyl terminal
      domain. Conversely, a region consisting of 16 amino acids in the juxtamembrane
      region (amino acids 227-242) in the carboxyl terminal tail of Cx43 was identified
      to be responsible for the association. A variant of Cx43 lacking this region was
      expressed only in a nonphosphorylated form and appeared to lose the capacity to
      localize to the region of cell-cell contact and dye transfer activity. When the
      expression of CIP150 was suppressed using small interfering RNA, the localization
      to the plasma membrane as well as dye transfer activity of Cx43 was significantly
      reduced. These results suggest that the newly identified domain is essential for
      the proper phosphorylation and localization of Cx43, and CIP150 is a novel
      partner protein targeting this domain.

PMID- 16112083
TI  - SNARE-mediated trafficking of alpha5beta1 integrin is required for spreading in
      CHO cells.
AB  - In this study, the role of SNARE-mediated membrane traffic in regulating integrin
      localization was examined and the requirement for SNARE function in cellular
      spreading was quantitatively assessed. Membrane traffic was inhibited with the
      VAMP-specific catalytic light chain from tetanus toxin (TeTx-LC), a dominant
      negative form (E329Q) of N-ethylmaleimide-sensitive fusion protein (NSF), and
      brefeldin A (BfA). Inhibition of membrane traffic with either E329Q-NSF or TeTx
      LC, but not BfA, significantly inhibited spreading of CHO cells on fibronectin.
      Spreading was rescued in TeTx-LC-expressing cells by co-transfection with a TeTx
      resistant cellubrevin/VAMP3. E329Q-NSF, a general inhibitor of SNARE function,
      was a more potent inhibitor of cell spreading than TeTx-LC, suggesting that
      tetanus toxin-insensitive SNAREs contribute to adhesion. It was found that E329Q
      NSF prevented trafficking of alpha5beta1 integrins from a central Rab11
      containing compartment to sites of protrusion during cell adhesion, while TeTx-LC
      delayed this trafficking. These results are consistent with a model of cellular
      adhesion that implicates SNARE function as an important component of integrin
      trafficking during the process of cell spreading.

PMID- 16112084
TI  - The ubiquitin ligase SCF(Grr1) is required for Gal2p degradation in the yeast
      Saccharomyces cerevisiae.
AB  - F-box proteins represent the substrate-specificity determinants of the SCF
      ubiquitin ligase complex. We previously reported that the F-box protein Grr1p is
      one of the proteins involved in the transmission of glucose-generated signal for
      proteolysis of the galactose transporter Gal2p and fructose-1,6-bisphosphatase.
      In this study, we show that the other components of SCF(Grr1), including Skp1,
      Rbx1p, and the ubiquitin-conjugating enzyme Cdc34, are also necessary for glucose
      induced Gal2p degradation. This suggests that transmission of the glucose signal
      involves an SCF(Grr1)-mediated ubiquitination step. However, almost
      superimposable ubiquitination patterns of Gal2p observed in wild-type and
      grr1Delta mutant cells imply that Gal2p is not the primary target of SCF(Grr1)
      ubiquitin ligase. In addition, we demonstrate here that glucose-induced Gal2p
      proteolysis is a cell-cycle-independent event.

PMID- 16112085
TI  - The influence of HER2 genotypes as molecular markers in ovarian cancer outcome.
AB  - A relevant clinical problem in the treatment of ovarian cancer (OC) is the
      development of resistance to chemotherapy, frequently due to genetic variations
      in enzymes and receptors. Changes in the HER2 receptor have been associated with
      breast and ovarian cancers. The role of a polymorphism in the HER2 gene in the
      clinical outcome of OC patients was investigated in this study. We characterized
      DNA samples from 111 patients with OC treated with cisplatin and paclitaxel,
      using PCR-RFLP. Our results indicate that patients carrying the valine
      homozygotic genotype present a lower overall survival mean, suggesting a role for
      this polymorphism in the outcome of ovarian cancer patients. The G allele has
      been implicated in the formation of active HER2 receptors, with a more aggressive
      phenotype. We hypothesize that HER2 genotypes can be predictive biomarkers in
      ovarian cancer, contributing to a genetic individual profile of great interest in
      clinical oncology.

PMID- 16112086
TI  - Signalling mechanisms of SDF-induced endothelial cell proliferation and
      migration.
AB  - The aim of our study was to investigate the effect of stromal-derived factor-1
      alpha (SDF-1-alpha) on endothelial angiogenic effects. SDF-1-alpha (50 ng/ml)
      increased the number of cultured endothelial cells from 33,653 +/- 1183 to 55,398
      +/- 2741, which significantly reduced by adding the BK(Ca)-inhibitor iberiotoxin,
      or the endothelial nitric oxide synthase-blocker, L-NMMA (n = 24, p < 0.05).
      Using the "Fences"-assay a significant increase of HUVEC migration induced by SDF
      1-alpha was reported, which was blocked by the addition of iberiotoxin or L-NMMA
      (n = 12, p < 0.05). BK(Ca) open-state probability (NPo) was analysed using the
      patch-clamp technique and NPo was increased from 0.003 (control) to 0.052 (SDF-1
      alpha; n = 10, p < 0.05). NO synthesis was measured using a cGMP
      radioimmunoassay. A significant increase of cGMP levels from 0.952 pmol/mg
      protein to 2.179 pmol/mg protein was observed, that was abolished by L-NMMA and
      significantly reduced by iberiotoxin (n=15, p<0.05). SDF-1-alpha increases
      endothelial proliferation and migration involving the activation of BK(Ca) and an
      increased production of NO.

PMID- 16112087
TI  - The mammalian formin FHOD1 interacts with the ERK MAP kinase pathway.
AB  - Formin homology 2 domain containing protein (FHOD1), a mammalian formin,
      regulates cytoskeletal architecture, enhances cell migration, and induces gene
      expression from the serum response element. In this study, we describe co
      precipitation of FHOD1 with components of the ERK MAP kinase pathway while co
      precipitation of FHOD1 with p38 MAP kinase and JNK was not observed. In addition,
      FHOD1 co-localized to lamellipodia with Raf-1 and to stress fibers with MEK.
      FHOD1-induced gene expression from the serum response element was dependent on
      ERK MAP kinase activation, and the native skeletal actin promoter were activated
      by FHOD1 through the SRF site. However, FHOD1-induced stress-fiber formation and
      gene expression from the skeletal actin promoter was independent of ERK
      activation. These novel data demonstrate that FHOD1-ERK MAP kinase interaction
      regulates key aspects of FHOD1 biology.

PMID- 16112088
TI  - IRAS, a candidate for I1-imidazoline receptor, mediates inhibitory effect of
      agmatine on cellular morphine dependence.
AB  - Agmatine, an endogenous ligand for the I1-imidazoline receptor, has previously
      been shown to prevent morphine dependence in rats and mice. To investigate the
      role of imidazoline receptor antisera-selected protein (IRAS), a strong candidate
      for I1R, in morphine dependence, two CHO cell lines were created, in which mu
      opioid receptor (MOR) was stably expressed alone (CHO-mu) or MOR and IRAS were
      stably co-expressed (CHO-mu/IRAS). After 48 h administration of morphine (10
      microM), naloxone induced a cAMP overshoot in both cell lines, suggesting
      cellular morphine dependence had been produced. Agmatine (0.1-2.5 microM)
      concentration-dependently inhibited the naloxone-precipitated cAMP overshoot when
      co-pretreated with morphine in CHO-mu/IRAS, but not in CHO-mu. Agmatine at 5-100
      microM also inhibited the cAMP overshoot in CHO/mu and CHO-mu/IRAS. Efaroxan, an
      I1R-preferential antagonist, completely blocked the effect of agmatine on the
      cAMP overshoot at 0.1-2.5 microM in CHO-mu/IRAS, while partially reversing the
      effects of agmatine at 5-100 microM. L-type calcium channel blocker nifedipine
      entirely mimicked the effects of agmatine at high concentrations on forskolin
      stimulated cAMP formation in CHO-mu and naloxone-precipitated cAMP overshoot in
      morphine-pretreated CHO-mu. Therefore, IRAS, in the co-transfected CHO-mu/IRAS
      cell line, appears necessary for low concentrations of agmatine to cause
      attenuation of cellular morphine dependence. An additional effect of agmatine at
      higher concentrations seems to relate to both transfected IRAS and some naive
      elements in CHO cells, and L-type voltage-gated calcium channels are not ruled
      out. This study suggests that IRAS mediates agmatine's high affinity effects on
      cellular morphine dependence and may play a role in opioid dependence.

PMID- 16112089
TI  - Spatiotemporal quantification of recruit and resident macrophages after crush
      nerve injury utilizing immunohistochemistry.
AB  - The purpose of this study was to investigate quantitatively the temporal and
      spatial regulation and the morphological changes of the recruit and resident
      macrophages in the sciatic nerve during Wallerian degeneration and the following
      regeneration using immunohistochemistry. Sciatic nerves in Sprague-Dawley (SD)
      rats were examined after nerve crush. The rats were anesthetized with 100 mg of
      ketamine and 20 mg of xylazine in a dose of 1 ml/kg by intraperitoneal injection.
      Anti-ED-1 antibody was used to detect phagocytic macrophage and anti-OX-6
      antibody was used to detect MHC class II cells. Few ED-1-immunopositive cells
      were seen within the normal sciatic nerve. After crush injury the number and the
      size of ED-1-immunopositive cells started to increase in all the segments distal
      to the crush site 3 days after injury and the number and size reached its peak on
      day 14 when the population of macrophage was 150 times higher in all the segments
      compared to controls. However, the number of ED-1-immunopositive cells and the
      size of the cells remains significantly high even after day 56 when functional
      recovery and axonal regeneration were complete. OX-6-immunopositive cells were
      observed within the control sciatic nerves. The number decreases significantly 3
      days after injury in all the segments distal to the crush site but showed no
      significant difference thereafter. There were also no significant differences in
      the cell areas. ED-1-immunopositive phagocytic macrophages show significant
      differences temporally in both the cell number and the size even after axonal
      regeneration.

PMID- 16112090
TI  - Molarless-induced changes of spines in hippocampal region of SAMP8 mice.
AB  - We examined the effect of the molarless condition on the dendritic spines of
      hippocampal pyramidal cells in SAMP8 mice in comparison to its effect on learning
      ability in a maze test. The molarless condition caused a decrease in the number
      of the spines of CA1 pyramidal cells only in the aged mice showing a reduced
      learning ability. The results suggest the involvement of the molarless condition
      in an attenuation of input activities in the hippocampal synapses.

PMID- 16112091
TI  - Vulnerability of synaptic plasticity in the complexin II knockout mouse to
      maternal deprivation stress.
AB  - The alterations in brain function and structure seen in schizophrenia are
      mediated by genetics as well as vulnerability due to environmental factors.
      Postmortem studies in schizophrenic patients have shown that expression of
      complexin II, which is involved in neurotransmitter release at central nervous
      system synapses, is decreased in the brain. We examined the physiological
      characteristics of complexin II gene-deficient mice subjected to maternal
      deprivation stress to determine whether psychological stress during the early
      stage of life affected the development of brain function. We compared the
      electrophysiological properties of CA1 hippocampal pyramidal neurons and spatial
      memory in the Morris water maze test in the wild-type mouse and the homozygous
      mutant. In the non-stressed mouse, no significant differences in transsynaptic
      responses and synaptic plasticity or spatial memory were seen, suggesting that
      complexin II does not play a critical role in transmitter release or synaptic
      plasticity under these conditions. In contrast, under conditions of maternal
      deprivation stress, the knockout mouse showed a significant decrease in post
      tetanic potentiation and LTP induction and a significant impairment in Morris
      water Maze test compared to the wild-type mouse, suggesting that complexin II
      plays a significant role in neurotransmitter release and synaptic plasticity
      under this pathological condition. Taken together, these results show that mice
      lacking complexin II are vulnerable to maternal deprivation stress, which raises
      the possibility that the complexin II gene may be a factor in the onset of
      schizophrenia.

PMID- 16112092
TI  - Rostro-caudal variations in neuronal size reflect the topography of cellular
      phenotypes in the rat superior cervical sympathetic ganglion.
AB  - The mammalian superior cervical ganglion (SCG) contains a complex mixture of
      neuronal phenotypes that selectively innervate different peripheral targets. The
      present study examined the rostro-caudal topography of sympathetic phenotypes in
      the rat SCG by analyzing the relation between cell position, size, and the
      expression of immunoreactivity for neuropeptide Y (NPY), calretinin, and
      calcitonin gene-related peptide (CGRP). We observed that 64% of SCG neurons
      expressed NPY and had an average diameter of approximately 24 microm throughout
      the ganglion. Previous studies indicate that most of these cells are
      vasoconstrictor in function. By contrast, the size of NPY-negative neurons varied
      from approximately 25 microm in the rostral ganglion near the internal carotid
      nerve to approximately 30 microm in the caudal ganglion between the external
      carotid nerve and cervical sympathetic trunk. Many of the large NPY-negative
      neurons in the caudal ganglion were surrounded by dense axonal baskets that were
      immunoreactive for calretinin and therefore are likely to be secretomotor neurons
      projecting to salivary glands. Consistent with earlier reports, the rostral
      ganglion contained low numbers of presumptive pupillomotor neurons, based on
      their expression of NPY and contact with fibers containing CGRP. The present
      results indicate that neuronal size may provide a useful aid to cellular
      identification, especially in the caudal ganglion, and they provide further
      evidence of a topographic organization within the mammalian SCG.

PMID- 16112093
TI  - Trans-resveratrol, a red wine ingredient, inhibits voltage-activated potassium
      currents in rat hippocampal neurons.
AB  - The red wine ingredient trans-resveratrol was found to exert potent
      neuroprotective effects in different in vivo and in vitro models. Thus far, the
      mechanisms underlying the neuroprotection were attributed mainly to its
      antioxidant properties. The aim of this study was to investigate the actions of
      trans-resveratrol on voltage-gated K(+) channels, which have been implicated in
      neuronal apoptosis. Superfusion of trans-resveratrol reversibly inhibited both
      the delayed rectifier (I(K)) and fast transient K(+) current (I(A)) in rat
      dissociated hippocampal neurons with IC(50) values of 13.6 +/- 1.0 microM and
      45.7 +/- 7.5 microM, respectively. The inhibition on I(K) had a slow onset, was
      neither voltage dependent nor use dependent. Trans-resveratrol (30 microM)
      shifted the steady-state inactivation curve of I(K) to the hyperpolarizing
      direction by 20 mV and slowed down its recovery from inactivation. The inhibition
      on I(A) was similar to that on I(K), but voltage dependent. Superfusion of trans
      resveratrol (30 microM) shifted the steady-state activation curve of I(A) to the
      depolarizing direction by 17 mV. Intracellular application of trans-resveratrol
      (30 microM) was ineffective. Based on the comparable effective concentrations,
      the inhibition of voltage-activated K(+) currents by trans-resveratrol may
      contribute to its neuroprotective effects.

PMID- 16112094
TI  - Effects of delayed intrathecal infusion of an NMDA receptor antagonist on
      ischemic injury and peri-infarct depolarizations.
AB  - The potent NMDA receptor antagonist, Conantokin-G (CGX-1007), a snail peptide,
      has an 8-h therapeutic window in rat focal cerebral ischemia. We hypothesized
      that the mechanism of neuroprotection is the inhibition of 'secondary phase' peri
      infarct depolarizations (PIDs), recently shown to recur 6--24 h post-reperfusion.
      Rats were implanted with intrathecal (i.t.) catheters for drug delivery and DC
      compatible electrodes for continuous PID monitoring and subjected to transient (2
      h) middle cerebral artery occlusion. Four groups were studied. In two groups
      (C(40)C and C(20)C), continuous infusion of CGX--1007 was administered over 8--24
      h post-occlusion at 0.1 microg/h (0.04 nmol/h) following either a 40- or 20-nmol
      bolus dose at 8 h. Another group (C(40)S) received the 40-nmol bolus followed by
      saline infusion, and a control group received saline. Intrathecal drug treatment
      reduced infarct volumes relative to controls by 61%, 31%, and 10% in C(40)C,
      C(40)S, and C(20)C groups, respectively, but also induced dose-dependent
      paralysis and elevated mortality. All rats had PID rates similar to the control
      group prior to treatment, but following treatment secondary phase PIDs were
      reduced by 47--57% in each drug group compared to controls. Because several
      animals exhibited PID inhibition but no neuroprotection, there was no significant
      correlation between these endpoints across groups. However, drug-treated animals
      that did not exhibit secondary phase PIDs prior to treatment had significantly
      smaller infarcts and reduced subsequent PID activity than corresponding control
      rats. Results suggest that post-reperfusion PIDs play a substantial, though still
      undefined pathogenic role in delayed maturation of cerebral infarction and NMDA
      receptor-targeted neuroprotection.

PMID- 16112095
TI  - Effects of repeated hyperbaric nitrogen-oxygen exposures on the striatal dopamine
      release and on motor disturbances in rats.
AB  - Previous studies have demonstrated disruptions of motor activities and a decrease
      of extracellular dopamine level in the striatum of rats exposed to high pressure
      of nitrogen. Men exposed to nitrogen pressure develop also motor and cognitive
      disturbances related to inert gas narcosis. After repetitive exposures,
      adaptation to narcosis was subjectively reported. To study the effects of
      repetitive exposures to hyperbaric nitrogen-oxygen, male Sprague-Dawley rats were
      implanted in the striatum with multifiber carbon dopamine-sensitive electrodes.
      After recovery from surgery, free-moving rats were exposed for 2 h up to 3 MPa of
      nitrogen-oxygen mixture before and after one daily exposure to 1 MPa of nitrogen
      oxygen, for 5 consecutive days. Dopamine release was measured by differential
      pulse voltammetry and motor activities were quantified using piezo-electric
      captor. At the first exposure to 3 MPa, the striatal dopamine level decreased
      during the compression (-15%) to reach -20% during the stay at 3 MPa. Motor
      activities were increased during compression (+15%) and the first 60 min at
      constant pressure (+10%). In contrast, at the second exposure to 3 MPa, an
      increase of dopamine of +15% was obtained during the whole exposure. However,
      total motor activities remained unchanged as compared to the first exposure. Our
      results confirm that nitrogen exposure at 3 MPa led to a decreased striatal
      dopamine release and increased motor disturbances in naive rats. Repetitive
      exposures to 1 MPa of nitrogen induced a reversal effect on the dopamine release
      which suggests a neurochemical change at the level of the neurotransmitter
      regulation processes of the basal ganglia. In contrast, motor activity remained
      quantitatively unchanged, thus suggesting that dopamine is not involved alone in
      modulating these motor disturbances.

PMID- 16112096
TI  - Focal cerebral ischemia induces changes in both MMP-13 and aggrecan around
      individual neurons.
AB  - INTRODUCTION: To test the hypothesis that matrix metalloprotease-13 (MMP-13) and
      aggrecan may play roles in post-ischemic neuronal pathophysiology, we examined
      the impact of middle cerebral artery occlusion/reperfusion (MCAO/R) on the
      abundance of these proteins in different regions of the infarct by
      immunohistochemistry (IHC) and Western blotting (WB). METHODS: The effect of
      MCAO/R on the abundance of MMP-13 and aggrecan was examined in 23 Wistar rats
      using antibodies against MMP-13 and aggrecan. BrdU was administered the last 2
      days of the experiment. The cellular source of the respective antigens was
      examined with fluorescent double labeling using the neuronal marker NeuN.
      Sections were also stained for BrdU. The ischemic zone was defined by MRI on T2
      weighted images and also on the tissue sections with the help of H and E
      counterstain. WB was performed for MMP-13. RESULTS: MMP-13 protein is highly
      induced in ischemic brain and is associated with neurons, whereas aggrecan is
      associated with the perineuronal matrix in non-ischemic brain. After 3 days of
      cerebral ischemia, the number of MMP-13 positive neurons in the periphery of the
      ischemic lesion increased compared to the respective area in the non-ischemic
      brain with a peak on day 7. A stronger staining for aggrecan was observed around
      MMP-13 positive neurons compared with other neurons. The majority of the MMP-13
      positive neurons in normal non-ischemic brain were also NeuN positive. BrdU was
      incorporated into MMP-13 positive neurons in the periphery of the infarct. WB
      confirmed this results by detecting MMP-13 bands in ischemic brains and activated
      MMP-13 up to 14 days after ischemia. CONCLUSIONS: There is a close spatial
      association of MMP-13 and aggrecan around individual neurons. Both MMP-13 and
      aggrecan appear to be involved in perineuronal matrix remodeling suggesting a
      role in neuronal reorganization after cerebral ischemia.

PMID- 16112097
TI  - Interference of chronically ingested copper in long-term potentiation (LTP) of
      rat hippocampus.
AB  - The objective of our study was to find the evidence of copper interaction in LTP,
      motivated by copper involvement in neurodegenerative illness, like Parkinson,
      Alzheimer and Amyotrophic Lateral Sclerosis, and we initiated the study of this
      element in the LTP. For this purpose we used hippocampus slices of rats
      chronically consuming copper dissolved in water (CuDR; n=26) and non-copper
      consuming rats (CR; n=20). The CuDR rats received 8--10 mg/day during 20--25
      days. Electrophysiological tests showed absence of LTP in CuDR slices, contrary
      to CR slices. The stimulus-response test applied before and after LTP showed
      significant increases of synaptic potential in the CR group. This did not occur
      in the CuDR group, except for the initial values, which probably seem associated
      to an early action of copper. The paired-pulse (PP) test, applied to CR and CuDR
      prior to tetanic stimulation, showed a significant reduction in PP, for the 20-,
      30- and 50-ms intervals in CuDR. At the end of the experiments, copper
      concentration was 54.2 times higher in CuDR slices, compared to the concentration
      present in CR slices. Our results show that copper reduces synaptic sensibility
      and also the facilitation capability. These effects represent a significant
      disturbance in the plasticity phenomenon associated with learning and memory.

PMID- 16112098
TI  - Delivery of Chlamydia pneumoniae to the vessel wall aggravates atherosclerosis in
      LDLr-/- mice.
AB  - OBJECTIVE: The role of Chlamydia pneumoniae in atherosclerosis is still debated.
      In this study a novel mouse model was applied to determine the direct impact of
      C. pneumoniae on the arterial wall and the development of atherosclerosis.
      METHODS: Direct effects of C. pneumoniae on collar-induced atherosclerosis were
      studied after local delivery of C. pneumoniae to carotid arteries of LDL receptor
      deficient (LDLr-/-) mice. RESULTS: The presence of C. pneumoniae in the vessel
      wall was quantified by RT-PCR (6.2 x 10(4) copies/artery) and resulted in a 2.0
      fold increase in intima/media ratios (p<0.05) and a 1.7-fold increase in stenosis
      (p<0.05). Immunostaining revealed a 2.98-fold (p<0.01) increased macrophage
      content and a tendency towards lower numbers of smooth muscle cells and collagen
      in lesions of infected carotid arteries. Direct delivery of another respiratory
      pathogen, Mycoplasma pneumoniae, to the carotids did not affect size or
      composition of the atherosclerotic lesions. Presence of C. pneumoniae in the
      carotid arteries resulted within 7 days in a marked upregulation of the
      expression of MCP-1 (p<0.01) and ICAM-1 as determined on mRNA and protein levels.
      These in vivo data were in line with data obtained with in vitro infections of
      macrophages and endothelial cells with C. pneumoniae. CONCLUSIONS: We conclude
      that C. pneumoniae in carotid arteries leads to more pronounced atherosclerotic
      lesions with a more vulnerable morphology and that this model is suitable to
      monitor direct effects of C. pneumoniae on atherogenesis.

PMID- 16112099
TI  - Proposal of automation of candidate reference method for the accurate serum
      cholesterol assay in clinical laboratories.
AB  - BACKGROUND: In 2001, Japan Society of Clinical Chemistry (JSCC) recommended the
      cholesterol dehydrogenase (CD)-UV method as a comparative method for serum
      cholesterol measurement in Japan. Although the CD-UV method is intended to
      standardize routine laboratory tests, it requires complex manipulations, and has
      been difficult to use for the evaluation of clinical laboratories. We therefore
      attempted to automate this method using reagents specified by JSCC and developed
      a simple automated method. METHODS: We evaluated the simple automated method
      using 2 general instruments (JCA-BM12 and H-7170S). The linearity was confirmed
      for the range over 15.52 mmol/l. The coefficients of variation for 20
      measurements of serum containing 2.5 and 6.1 mmol/l of cholesterol were < 1.0%,
      respectively. No interference by bilirubin, ditauro bilirubin, hemoglobin and
      chylomicrons was observed in this method. When measurement data with JCA-BM12
      were compared with those using the comparative method, the correlation
      coefficient was 0.999 (n=23), the regression formula was y=0.992x - 0.0036
      (mmol/l), and the bias was 0.8%. A similar data was obtained with H-7170S. Thus,
      in both comparisons, the bias was within the target (+/- 3.0%). CONCLUSIONS: This
      automated method provides a valid means of implementing the serum cholesterol
      measuring method recommended by JSCC.

PMID- 16112100
TI  - Foreword.

PMID- 16112101
TI  - Detection of Ggamma(Agammadeltabeta)0 thalassemia in North India.

PMID- 16112103
TI  - C. elegans TCF protein, POP-1, converts from repressor to activator as a result
      of Wnt-induced lowering of nuclear levels.
AB  - Canonical Wnt signaling converts the TCF/LEF transcription factor from repressor
      to activator by increasing nuclear levels of its coactivator, beta-catenin. A
      striking exception had been reported for Wnt-induced endoderm formation during C.
      elegans embryogenesis. It has long been believed that transcriptional activation
      of Wnt target genes in the endoderm precursor occurred due to a lowering of
      nuclear levels of the worm TCF/LEF protein, POP-1, effectively alleviating POP-1
      repressive activity. Contrary to this model, we demonstrate here that POP-1
      directly activates Wnt target genes in the endoderm precursor. Wnt converts POP-1
      from a repressor to an activator, and this conversion requires that POP-1 nuclear
      levels be lowered in the endoderm precursor. We propose that the balance between
      TCF/LEF and coactivator(s), achieved by elevating coactivator levels (the
      canonical pathway) and/or reducing TCF/LEF levels (worm endoderm), determines Wnt
      signal strength.

PMID- 16112102
TI  - Identification of shared transcriptional targets for the proneural bHLH factors
      Xath5 and XNeuroD.
AB  - Proneural basic helix-loop-helix (bHLH) transcription factors are critical
      positive regulators of neuronal differentiation in a variety of species and are
      required for proper differentiation of various subtypes of neurons. Although bHLH
      factors demonstrate some unique functions during neural development, they share
      the ability to regulate neuronal differentiation, potentially by targeting
      overlapping sets of genes. To assess this, we performed a screen in ectoderm
      animal cap tissue to identify direct transcriptional targets shared by two
      Xenopus ato-related bHLH factors, Xath5 and XNeuroD. Candidate target genes
      identified in this screen include several transcriptional regulators (Xebf2,
      Xebf3, XETOR and NKL), an RNA binding protein (elrC), a cell cycle component
      (Xgadd45gamma) and several novel genes. Overexpression of either Xath5 or XNeuroD
      induced ectopic in vivo expression of these candidate target genes. Conversely,
      blocking ato-related bHLH activity prevented endogenous nervous system expression
      of these genes. Therefore, we have identified a set of genes that can be
      regulated by multiple ato-related bHLH factors and may function as critical
      effectors of proneural bHLH-mediated differentiation.

PMID- 16112104
TI  - Role of Fyn kinase in signaling associated with epiboly during zebrafish
      development.
AB  - The function of Fyn kinase during zebrafish development through the blastula
      stage was investigated through the use of dominant-negative constructs designed
      to suppress the function of zebrafish c-Fyn. Microinjection of SH2 domain
      containing fusion protein or mRNA encoding the mutated, catalytically inactive
      Fyn at 45 min post-insemination had no significant effect during cleavage and did
      not inhibit formation of the yolk syncitial layer. Smoothing of the enveloping
      cell layer at the midblastula transition occurred normally and expression of
      bon/mixer and mezzo, zygotic transcription factors indicated that activation of
      the zygotic genome did occur. Signaling pathways involved with axis determination
      such as beta-catenin, activin, and nodal appeared to function normally as
      evidenced by expression of boz, goosecoid, and mezzo. However, while formation of
      the yolk syncitial layer was normal, the marginal blastomeres failed to migrate
      toward the vegetal pole and epiboly did not occur, a phenotype similar but
      distinct from that resulting from suppression of c-Yes kinase. The block to
      development was prevented by co-injection of c-Fyn mRNA with the dominant
      negative construct indicating that it was a specific effect. Injection of the
      dominant-negative mRNA into individual blastomeres indicated that the effect was
      exerted on the intrinsic ability of the individual blastomeres to respond to
      signals directing epiboly and not on the signals themselves. Analysis of the
      pattern of calcium signaling in experimental and control embryos demonstrated
      that the elevated [Ca2+]i characteristic of the marginal blastomeres was
      suppressed. Together, these observations indicate that Fyn kinase plays an
      important role in epiboly, possibly through its effects in calcium signaling.

PMID- 16112105
TI  - Interference of neutrophil-platelet interaction by YC-1: a cGMP-dependent manner
      on heterotypic cell-cell interaction.
AB  - N-Formyl-Met-Leu-Phe (fMLP) activated neutrophils and then induced neutrophil
      platelet complex formation in co-incubation condition. In addition, fMLP induce
      intracellular calcium mobilization in platelets, only when it is incubated along
      with neutrophils. This data established that fMLP-stimulated neutrophils activate
      platelets. 9E1, a monoclonal antibody of P-selectin, significantly blocks the
      formation of neutrophil-platelet complex induced by fMLP, indicating the
      involvement of P-selectin in the neutrophil-platelet complex formation. 3-(5'
      hydroxymethyl-2'-furyl-1-benzylindazole (YC-1), an unique nitric oxide
      independent activator of soluble guanylate cyclase, was evaluated for its effect
      on neutrophil-platelet complex. YC-1 inhibits fMLP-induced neutrophil-platelet
      complex formation in a concentration-dependent manner with an IC50 value of
      15.3+/-3.5 microM. However, this effect of YC-1 is partially reversed by pre
      treatment of 1H-(1,2,4)oxadiazolo[4,3-a]quinozalin-1-one (ODQ; 10 microM), which
      is a soluble guanylate cyclase inhibitor. Pre-treatment of either neutrophils or
      platelets with YC-1 (50 microM) prevent the fMLP-induced neutrophil-platelet
      complex formation, indicating that YC-1 could potentially exert its effects
      individually on either neutrophils or platelets alone. Cathepsin G released from
      fMLP-stimulated neutrophil activates the nearby platelets. YC-1 was also shown to
      inhibit this release of cathepsin G in a concentration-dependent manner. The IC50
      value was 6.2+/-0.2 microM. This inhibitory effect of YC-1 on cathepsin G release
      is reversed by ODQ (10 microM) and a protein kinase G inhibitor [1-oxo-9.12-epoxy
      1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-l][1,6]benzodiazocine-10-carbooxylic
      acid methyl ester (KT5835); 1 microM]. YC-1 inhibits cathepsin G-induced P
      selectin expression on human platelet at the IC50 value of 32.5+/-2.6 microM. A
      further study showed that YC-1 inhibits fMLP-induced neutrophil-platelet complex
      formation in whole blood at the IC50 value of 35.8+/-8.1 microM in a
      concentration-dependent manner. According to these data, it was hypothesized that
      fMLP stimulates neutrophils to release cathepsin G, which subsequently activates
      the nearby platelets, creating neutrophil-platelet complexes. YC-1 inhibits fMLP
      induced neutrophil from releasing cathepsin G via a cGMP-dependent pathway. This
      inhibitory effect of YC-1 on cathepsin G release is a major mechanism for
      affecting fMLP-induced neutrophil-platelet complex. YC-1's inhibition P-selectin
      expression on platelet may potentiate its effects. These inhibitory effects may
      contribute to the inhibition of neutrophil-platelet complex formation in whole
      blood.

PMID- 16112106
TI  - The effects of AMPA receptor antagonists in models of stroke and
      neurodegeneration.
AB  - Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
      antagonists have been shown to have neuroprotective effects in stroke models and
      although clinical trials with some agents are still ongoing, published results
      have not been favourable. We therefore wished to compare the effects of GYKI
      52466, GYKI 53405, EGIS-8332 and EGIS-10608, non-competitive AMPA receptor
      antagonists with homophthalazine chemical structures, in standard animal stroke
      models with effects in a neurodegenerative model--excitoxicity in newborn mice.
      All compounds inhibited the S-AMPA-induced spreading depression in the chicken
      retina, in vitro, and were potent anticonvulsants against maximal electroshock in
      mice, in vivo. The AMPA receptor antagonists prevented domoate-induced cell death
      of motoneurons, in vitro, and reduced infarct size in a dose-dependent manner in
      the permanent middle cerebral artery occlusion model in mice, in vivo. In newborn
      mice (P5, histopathology at P10), local injection of the AMPA receptor agonist S
      bromo-willardiine at day 5 after birth induced cortical damage and white matter
      damage, which was reduced in a dose-dependent manner by the AMPA receptor
      antagonists. EGIS 10608 was a very powerful receptor antagonist of white matter
      damage. In contrast, GYKI 52466 did not antagonize cortical and white matter
      damage induced by ibotenic acid. These models allow quantification of the effects
      of AMPA receptor antagonists in vitro and in vivo.

PMID- 16112107
TI  - Activation of PPARgamma is not involved in butyrate-induced epithelial cell
      differentiation.
AB  - Histone deacetylase-inhibitors affect growth and differentiation of intestinal
      epithelial cells by inducing expression of several transcription factors, e.g.
      Peroxisome proliferator-activated receptor gamma (PPARgamma) or vitamin D
      receptor (VDR). While activation of VDR by butyrate mainly seems to be
      responsible for cellular differentiation, the activation of PPARgamma in
      intestinal cells remains to be elucidated. The aim of this study was to determine
      the role of PPARgamma in butyrate-induced cell growth inhibition and
      differentiation induction in Caco-2 cells. Treatment with PPARgamma ligands
      ciglitazone and BADGE (bisphenol A diglycidyl) enhanced butyrate-induced cell
      growth inhibition in a dose- and time-dependent manner, whereas cell
      differentiation was unaffected after treatment with PPARgamma ligands
      rosiglitazone and MCC-555. Experiments were further performed in dominant
      negative PPARgamma mutant cells leading to an increase in cell growth whereas
      butyrate-induced cell differentiation was again unaffected. The present study
      clearly demonstrated that PPARgamma is involved in butyrate-induced inhibition of
      cell growth, but seems not to play an essential role in butyrate-induced cell
      differentiation.

PMID- 16112108
TI  - D53 (TPD52L1) is a cell cycle-regulated protein maximally expressed at the G2-M
      transition in breast cancer cells.
AB  - The cell commits to dividing during the G2-M transition, and timing of mitotic
      entry must be tightly regulated to ensure correct chromosome segregation.
      Identification of all proteins and molecular events that orchestrate the G2-M
      transition will be required for a complete understanding of the cell division
      cycle, and how its deregulation contributes to cell transformation. We have
      previously reported D53, a member of the tumor protein D52 family, to be a novel
      14-3-3 partner protein in breast cancer cells. We now report that D53 expression
      is highly upregulated at the G2-M transition in breast cancer cell lines in which
      D53 is endogenously or exogenously expressed. The timing and subcellular
      localization of D53 expression paralleled that of cyclin B1, and D53 expression
      was similarly regulated at both post-transcriptional and post-translational
      levels. Interactions between D53 and 14-3-3, a negative regulator of the G2-M
      transition, were increased in synchronized populations enriched for cells in G2/M
      phases, compared with G1/S arrested cells. Enforced expression of two EGFP-tagged
      D53 isoforms and the related protein D52 produced high proportions of
      multinucleated MDA-MB-231 breast carcinoma cells. These results identify D53 as a
      cell cycle-regulated protein whose deregulated expression can adversely affect
      the completion of mitosis.

PMID- 16112109
TI  - Ischemia injury alters endothelial cell properties of kidney cortex: stimulation
      of MMP-9.
AB  - Although ischemia is the leading cause of acute renal failure in human, there is
      little information on the remodeling the kidney endothelium matrix during
      ischemic injury. In this study, we investigated the activity and expression of
      MMP-2 and MMP-9, in an isolated endothelial fraction following an acute in vivo
      reversible ischemia induced in rats by vascular clamping. Ischemia increased
      serum creatinine levels 1.4-fold, hallmark of acute renal failure. Isolation of
      the endothelial cell fraction was performed by affinity chromatography using an
      anti-PECAM-1 antibody. The isolated fraction was assessed by Western blotting
      analysis of endothelial cell markers. The positively selected fractions were
      enriched in the endothelial markers eNOS and PECAM-1 by 128-fold and 44-fold,
      respectively. Gelatin zymography showed that ischemia strongly stimulated
      proteolytic activity of proMMP-2 (1.8-fold), proMMP-9 (3-fold) and MMP-9 (4-fold)
      in the endothelial fractions. Western blot analysis indicated that TIMP-2 protein
      level increased by 3.2-fold in the endothelial fractions during ischemia.
      Surprisingly, TIMP-1 was absent from the endothelial preparations but was easily
      detected in the non-endothelial cells. Levels of the endocytic receptor LRP were
      increased by 2-fold during ischemia in the endothelial fractions. Occludin, a
      known in vivo MMP-9 substrate, was partly degraded in the endothelial fractions
      during ischemia, suggesting that the MMP-9 which was upregulated during ischemia
      was functional. These data suggest that ischemia in kidney could lead to the
      degradation of the vascular basement membrane and to increased permeability. This
      suggests new therapeutic approaches for ischemic pathologies by targeting MMP-9
      and its regulators.

PMID- 16112110
TI  - Epigenetic silencing in embryogenesis.
AB  - Transcription profiling of early embryos emphasizes that differential gene
      expression is a fundamental control mechanism of development. Precise regulatory
      mechanisms operate on a background of epigenetic changes in chromatin
      composition, modification, and architecture that are integral for the development
      of a pluripotent embryo into an adult.

PMID- 16112111
TI  - Hepatocyte growth factor enhances CXCR4 expression favoring breast cancer cell
      invasiveness.
AB  - Microenvironmental factors affect different aspects of tumor cell biology,
      including cell survival, invasion, and metastasis. Here, we report that
      hepatocyte growth factor and hypoxia may contribute to breast carcinoma cell
      invasiveness by inducing the chemokine receptor CXCR4. Hepatocyte growth factor
      enhanced CXCR4 mRNA and protein expression exclusively in MCF-7 (low invasive)
      carcinoma cells, while in response to hypoxia, CXCR4 induction was observed in
      both MCF-7 and MDA-MB 231 (highly invasive) carcinoma cells. The receptor
      induction had a functional role in cancer cells, as demonstrated by the fact that
      hepatocyte growth factor pretreatment promoted MCF-7 cell migration toward the
      CXCR4-specific ligand CXCL12. Extracellular signal-regulated protein kinase 1/2
      (ERK1/2) and phosphoinositide-3-kinase (PI3K) transduction pathways seemed to be
      differently implicated in the early induction of CXCR4 by hepatocyte growth
      factor or hypoxia in the two breast carcinoma cells examined.

PMID- 16112112
TI  - Progenitor proliferation in the adult hippocampus and substantia nigra induced by
      glial cell line-derived neurotrophic factor.
AB  - Neurogenesis is an ongoing process in the hippocampus and olfactory bulb of adult
      mammals, regulated in part by trophic factors. While glial cell line-derived
      neurotrophic factor (GDNF) is being directly delivered into the nigrostriatal
      system of the brain for the treatment of Parkinson's disease in clinical trials,
      little is known about its effects on cell genesis in the brain. Here, we
      investigated the effects of GDNF on progenitor cell proliferation and
      differentiation in two GDNF-responsive areas, the hippocampus and substantia
      nigra. GDNF (18 microg/day) was infused in the striatum of 2-month-old Sprague
      Dawley rats for 28 days. New cells were identified by the nuclear incorporation
      of 5-bromo-2-deoxyuridine (BrdU) and analyzed by light and electron microscopic
      immunostaining and quantitative morphometric techniques. GDNF significantly
      increased cell proliferation in the hippocampus by 78% and in the substantia
      nigra by 52%. There was no evidence of neurogenesis in the substantia nigra, with
      new cells displaying glial features and none of the 1549 BrdU-positive cells co
      labeled for the dopamine neuronal marker tyrosine hydroxylase (TH). Rather, GDNF
      upregulated TH in existing neurons, consistent with the restorative actions of
      this tropic factor. The hippocampus is a site that supports adult neurogenesis
      and new cells generated here were closely associated with granule cells in the
      dentate gyrus. Some were double labeled for the neuronal marker NeuN; others had
      features of astrocytes, the principal source of new adult neurons in the
      hippocampus. The effects of GDNF on the hippocampus are potentially important in
      memory and learning processes.

PMID- 16112113
TI  - Activation of p53 and the pro-apoptotic p53 target gene PUMA during
      depolarization-induced apoptosis of chromaffin cells.
AB  - The pathogenesis of non-glutamatergic, depolarization-induced cell death is still
      enigmatic. Recently, we have shown that veratridine induces apoptosis in
      chromaffin cells, and we have demonstrated protective effects of antioxidants in
      this system, suggesting a role for Na+ channels and oxidative stress in
      depolarization-induced cell death. We examined the possible contribution of p53,
      a transcription factor that has a major role in determining cell fate, and the
      mitochondrial apoptosis pathway in veratridine-induced cell death of cultured
      bovine chromaffin cells. Nuclear condensation and fragmentation were detected
      several hours after a 60-min exposure to 30 microM veratridine. Apoptosis was
      associated with a transitory increase in p53 protein levels. Veratridine induced
      transcription of the pro-apoptotic p53 target gene PUMA, but not of bax or pig3.
      Using transient transfection experiments, we found that wild-type p53, but not
      the mutant form p53-273H, was sufficient to induce cell death in the chromaffin
      cells, which was caspase-9 dependent. The down-regulation of either p53, by
      overexpressing p53-273H, or caspase-9 activity using a dominant-negative caspase
      9 mutant protected chromaffin cells against veratridine-induced toxicity. Our
      data demonstrate the importance of p53 and the downstream activation of the
      mitochondrial apoptosis pathway in depolarization-induced apoptosis.

PMID- 16112114
TI  - Intravitreal macrophage activation enables cat retinal ganglion cells to
      regenerate injured axons into the mature optic nerve.
AB  - In mature mammals, retinal ganglion cells (RGCs) are generally unable to
      regenerate injured axons into the optic nerve. Here, we report that an
      intravitreal injection of either of two macrophage activators, oxidized galectin
      1 or zymosan, strongly enhanced the regeneration of transected RGC axons beyond
      an optic nerve crush site in adult cats. Using WGA-HRP as an anterograde tracer,
      we found that injection of either macrophage activator caused many axons to grow
      into the distal optic nerve when evaluated 14 days later, with the strongest
      effects seen after injecting 100 ng of galectin-1. Elongation continued for at
      least another 2 weeks. Control eyes injected with saline contained very few
      labeled axons extending across the crush site. Elevation of intracellular cAMP
      levels using forskolin also enhanced regeneration beyond the crush site to some
      extent, but this treatment did not augment the effect of galectin-1 any further.
      These results indicate that RGCs of adult cats are capable of reverting to an
      active growth state and at least partially overcoming an inhibitory CNS
      environment as a result of intravitreal macrophage activation.

PMID- 16112115
TI  - Developmental effects of oxytocin on neural activation and neuropeptide release
      in response to social stimuli.
AB  - Previous studies have revealed that the neuropeptide hormone oxytocin (OT) has
      developmental effects on subsequent social behavior and on mechanisms underlying
      social behavior such as OT neurons and estrogen receptor alpha. This suggests
      that OT might also have developmental effects on neural responses to social
      stimuli. This was tested in socially monogamous prairie voles (Microtus
      ochrogaster) by manipulating OT on the first day of life and then assessing the
      response to a heterosexual pairing in adulthood. The response to cohabitation was
      assessed by quantifying neural activation in regions of the brain associated with
      sociosexual behavior and anxiety using c-Fos immunoreactivity. Additionally,
      immunocytochemistry was used to label OT and vasopressin neurons and plasma was
      assayed for both neuropeptides. Treatment effects were evident in females, but
      not in males. Blockade of OT receptors with an OT antagonist on the first day of
      life resulted in neural activation of the central amygdala in response to a
      pairing with a novel male in adulthood. The central amygdala does not normally
      express c-Fos after a heterosexual pairing in reproductively naive prairie voles.
      Treatment effects also were observed in vasopressin immunoreactivity in the SON
      with OT-treated females showing a decrease.

PMID- 16112116
TI  - Behavioral neuroendocrinology evolving: contributions of comparative and field
      studies.

PMID- 16112117
TI  - Androgen metabolism and the activation of male sexual behavior: it's more
      complicated than you think!

PMID- 16112118
TI  - Correlates for a low ankle-brachial index in elderly Chinese.
AB  - This study examines the prevalence of atherosclerosis (using ankle-brachial index
      (ABI) value <0.9) and associated socioeconomic and lifestyle factors in elderly
      Chinese, adjusting for presence of cardiovascular diseases and body mass index,
      in a cross-sectional survey of 1999 men and 1999 women aged 65 years and over
      living in the community. A questionnaire containing information regarding
      socioeconomic status, medical history and lifestyle factors was administered.
      Measurement included height, weight, percentage body fat using dual-energy X-ray
      absorptiometry and ABI. The Hong Kong population (2000) age adjusted prevalence
      of ABI <0.9 was 5.3% for men and 11.0% for women. In multivariate analysis, old
      age, female gender, presence of cardiovascular diseases, cognitive impairment,
      prolonged 6 m walk, smoking habit and alcohol intake were positively associated
      with ABI <0.9, while negative associations were observed with Vitamin C intake
      >100 mg per day, with the lowest OR for the range 141-190 mg (OR 0.4). Physical
      activity level, and self rated higher social standing in the community, while
      significant in univariate analysis, were not included as independent significant
      factors in the multivariate model. Lifestyle factors and the female gender were
      independent risk factors for atherosclerosis in the elderly Chinese population.

PMID- 16112119
TI  - Beta-lipoprotein- and LDL-associated serum gamma-glutamyltransferase in patients
      with coronary atherosclerosis.
AB  - Elevation of serum gamma-glutamyltransferase (GGT) activity is a risk factor for
      myocardial infarction and stroke. GGT activity can catalyze the oxidation of low
      density lipoprotein (LDL), a process involved in the pathogenesis of
      atherosclerosis. Serum GGT is partially adsorbed onto circulating LDL, and
      catalytically active GGT has been found within atherosclerotic plaques,
      colocalizing with oxidized LDL and foam cells. We investigated the the nature of
      the LDL-associated GGT, the degree of correlation between total serum GGT levels
      and beta-lipoprotein (beta-LP)-associated GGT, and whether this association is
      altered in subjects with coronary artery disease (CAD). LDL-bound GGT showed an
      entire, amphiphilic heavy chain, but the association was easily lost during LDL
      purification by affinity chromatography. When the activity of GGT associated with
      polycation-precipitated beta-lipoproteins was assayed, an identical
      immunoreactive GGT was found in Western blot, and a statistically significant
      linear correlation was found between total serum GGT levels and the corresponding
      beta-LP-bound activities (p<0.0001) in controls and patients with CAD.
      Nevertheless, subjects with CAD presented a lower ratio of beta-LP-bound GGT to
      total serum GGT respect to controls (p<0.05) and healthy subjects with elevated
      serum GGT (p<0.01). In addition, a relative decrease of total serum GGT was
      observed in CAD subjects of older age as compared to younger ones (p<0.005).

PMID- 16112120
TI  - Association between nutrient intake and peripheral artery disease: results from
      the InCHIANTI study.
AB  - BACKGROUND: Little is known about the relationship between dietary patterns and
      peripheral arterial disease (PAD). Our aim was to estimate the association
      between nutrient intake and diagnosis of PAD. METHODS AND RESULTS: We assessed
      the nutrient intake of 1251 home-dwelling subjects enrolled in the InCHIANTI
      study, mean age 68 years (S.D.: 15). We explored the relationship between
      nutrient intake, obtained through the European Prospective Investigation into
      Cancer and Nutrition (EPIC) questionnaire, and PAD, defined as an ankle-brachial
      index (ABI)<0.90. After adjustment for potential confounders, we found a
      reduction of the risk of having an ABI<0.90 associated with vegetable lipid
      intake>or=34.4 g/day (OR: 0.39; 95% CI: 0.16-0.97), Vitamin E intake>or=7.726
      mg/day (OR: 0.37; 95% CI 0.16-0.84) and higher serum HDL cholesterol
      concentration (OR: 0.76; 95% CI: 0.63-0.92 for 10mg/dl increase). Age (OR: 1.11;
      95% CI 1.07-1.14 for 1 year increase), smoking (OR: 1.03; 95% CI: 1.01-1.04 for
      10 packs/year increase) and pulse pressure (OR: 1.11; 95% CI: 1.03-1.19 for 5
      mmHg increase) were associated with an increased risk of PAD. CONCLUSIONS: A
      higher intake of vegetable lipids, Vitamin E and higher concentrations of serum
      HDL cholesterol characterize subjects free from PAD. Prospective studies are
      needed to verify whether this dietary pattern and/or interventions aimed at
      increasing HDL cholesterol exert some protective effect against PAD.

PMID- 16112121
TI  - Statins inhibit hypoxia-induced endothelial proliferation by preventing calcium
      induced ROS formation.
AB  - Pathological hypoxia plays an important role in many diseases, such as
      atherosclerosis, cancer, and rheumatoid arthritis. The aim of the present study
      was to examine the effects of different statins on hypoxia-induced endothelial
      cell signalling. Human umbilical cord vein endothelial cells (HUVEC) were treated
      with NaCN (CN, 2.5 mmol/l) to simulate a transient hypoxia. The CN-induced
      increase of endothelial cell numbers was significantly (n = 10, p < 0.01) reduced
      by the Ca(2+) chelator BAPTA (10 micromol/l), or the reactive oxygen species
      (ROS) scavenger N-acetylcysteine (ACC, 1 mmol/l), or the NAD(P)H-oxidase
      inhibitor diphenyleneiodonium (DPI, 5 micromol/l). In detail, cell numbers were
      (in percentage of control): 163.24 (CN), 90.06 (CN+ACC), 92.06 (CN+DPI).
      Intracellular-Ca(2+) and -ROS, analysed by fluorescence imaging, were
      significantly increased by CN. Interestingly, the CN-induced increase of ROS was
      in part Ca(2+)-dependent, whereas the Ca(2+) increase was not ROS-dependent.
      Simvastatin (5 micromol/l), fluvastatin (2.5 micromol/l), and cerivastatin (0.1
      micromol/l) all reduced CN-induced proliferation, ROS generation and Ca(2+)
      increase. Cell viability was not reduced by the statins and the antiproliferative
      effect was completely reversed by mevalonate (500 micromol/l). In conclusion our
      study demonstrates that statins block hypoxia-associated endothelial
      proliferation by preventing the increase of Ca(2+) and ROS.

PMID- 16112122
TI  - Severe hyperlipidemia causes impaired renin-angiotensin system function in
      apolipoprotein E deficient mice.
AB  - Dyslipidemia is a known risk factor for cardiovascular diseases and may associate
      with renal injury. Using mouse models with various degrees of
      hypercholesterolemia and hypertryliceridemia, we investigated the effects of
      lipids on the renin-angiotensin system (RAS). ApoE-/- mice were fed either a high
      fat diet (HF-ApoE-/-; mice developed hypertriglyceridemia and severe
      hypercholesterolemia) or regular chow (R-ApoE(-/-); mice developed less severe
      hypercholesterolemia only). Renal histopathology in the HF-ApoE-/- revealed
      massive lipid accumulation especially at the glomerular vascular pole. In these
      mice plasma renin concentration was significantly reduced (489+/-111 ng/(ml h)
      versus 1023+/-90 ng/(ml h) in R-ApoE-/- mice) and blood pressure was consequently
      significantly lower than in R-ApoE-/- (104+/-2 mmHg versus 115+/-2 mmHg,
      respectively). A model of renin-dependent renovascular hypertension (two-kidney,
      one clip) was generated and HF-ApoE-/- mice proved unable to increase renin
      secretion, and blood pressure, in response to diminished renal perfusion as
      compared to regular chow fed mice (665+/-90 ng/(ml h) versus 2393+/-372 ng/(ml
      h), respectively and 106+/-3 mmHg versus 140+/-2 mmHg, respectively).
      Hypertriglyceridemia and severe hypercholesterolemia are associated with renal
      lipid deposition and impaired renin secretion in ApoE-/- mice exposed to high fat
      diet. These observations further characterize the phenotype of this widely used
      mouse model and provide a rationale for the use of these mice to study lipid
      induced organ damage.

PMID- 16112123
TI  - Modification of the NCEP ATP III definitions of the metabolic syndrome for use in
      Asians identifies individuals at risk of ischemic heart disease.
AB  - The association between the metabolic syndrome (MS) to ischemic heart disease
      (IHD) has not been established prospectively in Asian populations. We carried out
      registry linkage, using unique national identity numbers, to identify incident
      IHD events in subjects without diabetes mellitus or IHD from two cross-sectional
      studies of Chinese, Malays and Asian Indians living in Singapore. The risk of IHD
      associated with the MS (NCEP ATP III criteria) was determined by Cox-proportional
      hazards regression before and after adjustment for age, sex, ethnic group and
      current cigarette smoking. We also assessed the utility of modified Asian
      criteria (reducing the waist circumference (WC) used to define central obesity to
      90 cm in men and 80 cm in women) on the risk of IHD associated with the MS. This
      study provided 38,157.4 person-years in 4042 subjects who experienced 93 incident
      IHD events. MS (as defined by the NCEP ATP III criteria) was associated with
      increased risk of IHD (HR3.09; 95% CI 1.96-4.88). Those who satisfied only the
      modified Asian criteria, but not the NCEP ATP III criteria, were also at
      increased risk of IHD (HR 2.13; 95% CI 0.99-4.58). It would be appropriate to
      lower the cut-off for WC used for the diagnosis of the MS in such populations.

PMID- 16112124
TI  - Microdamage: a cell transducing mechanism based on ruptured osteocyte processes.
AB  - As a result of underlying pathological diseases, such as osteoporosis,
      osteopenia, or due to altered loading after joint replacements, bones become more
      susceptible to microdamage accumulation than those of normal human beings, as are
      those of athletes who undertake strenuous exercise [Stromsoe, 2004. Fracture
      fixation problems in osteoporosis. Injury 35, 107-113]. Experimental evidence has
      linked bone adaptation to microdamage, and to increased cell activity. In this
      work, we investigated whether microcrack detection is related to rupturing of the
      cellular material itself due to crack face displacements. Using specific cell
      staining techniques, it was confirmed that relative crack displacements are
      capable of tearing cell processes between neighbouring osteocytes. No ruptured
      cell processes were found near the crack tip where the displacements are less.
      Rupturing of cell processes due to crack opening and shear displacement is a
      feasible new mechanism by which bone can detect and estimate the size of a
      microcrack. Ruptured cell processes may directly secrete passive and active
      components in the extracellular matrix, triggering a repair response.

PMID- 16112125
TI  - Flow properties of freshly prepared ettringite suspensions in water at 25 degrees
      C.
AB  - The rheology of a complex, heterogeneous mineral colloid was rationalised using
      models devised for model rod systems. Mixing a calcium hydroxide slurry with an
      aluminium sulphate solution produces a suspension of rod-shaped ettringite
      particles. Ettringite rod suspensions exhibit non-Newtonian flow behaviour, which
      depends on the shape of the particles, their size distribution, concentration and
      surface properties as well as the suspension medium characteristics. We have
      measured the shear viscosity of suspensions of ettringite rods with a median
      aspect ratio, r(i) approximately 8, at 25 degrees C as a function of particle
      volume fraction, phi, in the range 0.0001-0.08. It was found that the viscosity
      of the suspensions increased with phi, and showed a marked change of slope at phi
      approximately 0.01, which we identified as the minimum overlap concentration
      phi(*). Above phi(*), the system is in the semi-dilute regime. At phi>phi(*),
      when Pe(rot)>1, hydrodynamic interactions between rods become increasingly
      significant, and we observe shear-thinning behaviour. The high effective
      hydrodynamic volume of rotating rods, resulting in much lower values of the
      maximum packing fraction, phi(c), than for spheres, dominates the rheological
      behaviour of ettringite suspensions.

PMID- 16112126
TI  - Influence of viscous dissipation and thermophoresis on Darcy-Forchheimer mixed
      convection in a fluid saturated porous media.
AB  - Mixed convection flow, heat, and mass transfer about an isothermal vertical flat
      plate embedded in a fluid-saturated porous medium and the effects of viscous
      dissipation and thermophoresis in both aiding and opposing flows are analyzed.
      The similarity solution is used to transform the problem under consideration into
      a boundary value problem of coupled ordinary differential equations, which are
      solved numerically by using the shooting method. Numerical computations are
      carried out for the non-dimensional physical parameter. The results are analyzed
      for the effect of different physical parameters such as thermophoretic, mixed
      convection, inertia parameter, buoyancy ratio, and Schmid number on the flow,
      heat, and mass transfer characteristics. Two cases are considered, one
      corresponding to the presence of viscous dissipation and the other to the absence
      of it.

PMID- 16112127
TI  - Pyrene absorption can be a convenient method for probing critical micellar
      concentration (cmc) and indexing micellar polarity.
AB  - The critical micellar concentration (cmc) of both ionic and non-ionic surfactants
      can be conveniently determined from the measurements of UV absorption of pyrene
      in surfactant solution. The results on a number of surfactants have agreed with
      that realized from pyrene fluorescence measurements as well as that obtained
      following conductometric, tensiometric and calorimetric methods. The absorbance
      vs [surfactant] profiles for all the major UV spectral peaks of pyrene have been
      found to be sigmoidal in nature which were analyzed according to Sigmoidal
      Boltzmann equation (SBE) to evaluate the cmcs of the studied surfactants. The
      difference between the initial and the final asymptotes (a(i) and a(f),
      respectively) of the sigmoidal profile, Delta a = (a(f)-a(i)) and the slope of
      the sigmoid, S(sig) have been observed to depend on the type of the surfactant.
      The Delta a has shown a linear correlation with the ratio of the fluorescence
      intensities of the first and the third vibronic peaks, I1/I3 of pyrene which is
      considered as a measure of the environmental polarity (herein micellar interior)
      of the probe (pyrene). Thus, Delta a values have the prospect for use as another
      index for the estimation of polarity of micellar interior.

PMID- 16112128
TI  - Microstructuring of phospholipid bilayers on gold surfaces by micromolding in
      capillaries.
AB  - Microstructuring of lipid bilayers on gold surfaces was achieved by micromolding
      in capillaries employing chemically modified polydimethylsiloxane (PDMS).
      Microfluidic networks of PDMS were prepared by micromolding and functionalized
      with thiol end-groups using 3-mercaptopropyltrimethoxysilane. The PDMS stamps
      were firmly attached to the gold substrate via quasi-covalent linkage providing a
      tight seal, a prerequisite for establishing individual addressable capillaries.
      Bilayers composed of POPC/POPG were subsequently prepared on microstructured self
      assembly monolayers of 11-amino-1-undecanethiol via strong electrostatic
      interactions. This way it is possible to generate individually addressable lipid
      bilayers on gold surfaces, a procedure, which is of widespread interest for
      investigating protein lipid interactions with microscopic techniques.

PMID- 16112129
TI  - The mu-derivative and its applications to finding exact solutions of the Cahn
      Hilliard, Korteveg-de Vries, and Burgers equations.
AB  - A new transformation termed the mu-derivative is introduced. Applying it to the
      Cahn-Hilliard equation yields dynamical exact solutions. It is shown that the mu
      transformed Cahn-Hilliard equation can be presented in a separable form. This
      transformation also yields dynamical exact solutions and separable forms for
      other nonlinear models such as the modified Korteveg-de Vries and the Burgers
      equations. The general structure of a nonlinear partial differential equation
      that becomes separable upon applying the mu-derivative is described.

PMID- 16112130
TI  - Remarks on the shear viscosity of surfaces stabilised with soluble surfactants.
AB  - A survey is made of previously reported values of the surface shear viscosity of
      sodium dodecyl sulphate solution which reveals inconsistencies. The origin of
      these inconsistencies is thought to be due to the fact that, because SDS is a
      soluble surfactant, the surface deformation rate is governed by a three
      dimensional sublayer adjacent to the surface and is therefore inherently
      experiment-dependent. Because of this, only an apparent surface shear viscosity
      that is specific to a particular experiment can be measured. However, for an
      insoluble surfactant, an intrinsic two-dimensional surface viscosity can be
      clearly defined. Some methods of measuring an apparent surface shear viscosity
      assume that the surface shear viscosity is the only surface property that
      determines the drainage rate from foam or individual Plateau borders but there is
      experimental evidence to show that other surface properties may be significant.

PMID- 16112131
TI  - Mono-layer of Ni(100-x)Fe(x) nanoparticles fabricated on a polyimide film under
      different curing atmospheres.
AB  - A mono-layer of nano-sized metal particles was prepared on the surface of a
      polyimide film by simply depositing a thin film of Ni80Fe20 on top of the
      polyamic acid that was spin coated onto a Si wafer. During thermal imidization of
      the polyamic acid film, Fe was selectively etched by reacting with the carbonyl
      group of the polyamic acid to leave behind uniformly distributed Ni-rich metallic
      particles. The average diameter of the particles was 4 nm and the particles were
      confined into a single layer on top of the polymer film. Moreover, it was also
      shown that the morphology of the nanoparticles can be substantially altered by
      curing the precursor film in a hydrogen atmosphere, without significantly
      damaging the polymer film. Thus produced nanoparticles lay exposed on top of the
      electrically insulating and chemically stable polymer film so that it is possible
      that the nanoparticles can be directly used for fabricating a nonvolatile flash
      memory device or as a template for building functional nano-structures.

PMID- 16112132
TI  - Proceedings of the 8th International Workshop on Human Leucocyte Differentiation
      Antigens, Adelaide, Australia, 2000-2004.

PMID- 16112133
TI  - Changes in membrane lipid composition following rapid cold hardening in
      Drosophila melanogaster.
AB  - Naturally occurring diurnal variations in temperature are sufficient to induce a
      rapid cold hardening (RCH) response in insects. RCH can increase cold tolerance
      by 1-2 degrees C and extend the temperature interval at which insects can remain
      active. While the benefits of RCH are well established, the underlying
      physiological mechanisms remain unresolved. In this study we investigated the
      role of RCH on expression of heat shock proteins (Hsp70) after a cold shock, and
      the effect of RCH on the composition of phospholipid fatty acids (PLFAs) in
      membranes of Drosophila melanogaster. These experiments were performed on both
      "control" flies and flies selected for cold resistance in order to additionally
      examine a possible target for selection for cold tolerance. RCH improved survival
      following cold shock at -4, -6 and -8 degrees C. No induction of Hsp70 was found
      following cold shock irrespective of the pre-treatment. In contrast, a 5h RCH
      treatment was sufficient to induce small, but significant, changes in the
      composition of PLFAs. Here, the polyunsaturated linoleic acid, 18:2(n-6),
      increased while monounsaturated (18:1) and saturated (14:0) PLFAs decreased in
      abundance. These changes were observed in both selection groups and caused a
      significant increase in the overall degree of unsaturation. This response is
      consistent with the membrane response typically found during cold acclimation in
      ectothermic animals and it is likely adaptive to maintain membrane function
      during cold. Cold selection resulted in PLFA changes (decrease of 18:0 and 18:1
      and increase of 14:0 and 16:1), which may improve the ability to harden during
      RCH.

PMID- 16112134
TI  - Effects of luminal ATPase inhibitors on electrogenic ion transport in rat distal
      colon.
AB  - BACKGROUND: The involvement of transport proteins, other than chloride channels,
      expressed in the luminal membrane of epithelial cells in regulated chloride
      secretion in native colon remains poorly understood. There are at least two
      distinct ATPases expressed in the apical membrane of rat colonocytes. They can be
      distinguished by their different sensitivity to the vanadium-derived compound
      orthovanadate. The objective was to study the effects of luminal ATPase
      inhibitors on regulated chloride secretion using elecrophysiological and
      pharmacological approaches. MATERIALS AND METHODS: Unstripped rat distal colon
      segments were mounted in Ussing chambers. Potential difference, transepithelial
      resistance, and short-circuit current across unstripped colon segments were
      monitored with a dual voltage/current clamp. RESULTS: Luminal application of
      VO4(3-) did not alter baseline electrical values in rat distal colon but dose
      dependently inhibited forskolin-stimulated Isc. Luminal ouabain (1 mm) did not
      blunt the response to the cAMP agonist. The inhibitory effect of luminal VO4(3-)
      occurred at a site distal to cAMP generation and was rather specific for the
      cyclic nucleotide-dependent signaling pathway, because the response to the Ca2+
      agonist carbachol was largely preserved. CONCLUSION: VO4(3-) inhibits cAMP
      stimulated Cl- secretion in rat distal colon at a site distal to cAMP generation
      without altering intestinal permeability. Ouabain-sensitive luminal K+-ATPases do
      not seem to contribute to forskolin-stimulated electrogenic ion transport. These
      findings may suggest new therapeutic targets for secretory diarrhea.

PMID- 16112135
TI  - Role of Kupffer cells in lung injury in rats administered endotoxin 1.
AB  - The purpose of this study was to investigate the regulation of lung macrophages
      (Muvarphis) by Kupffer cells (KCs) in lung injury caused by endotoxemia.
      Phenotypic differences in tissue Muvarphis were also investigated. Muvarphis were
      isolated from gadolinium chloride (GdCl(3))- or saline-treated rats 2 h after
      saline or lipopolysaccharide (LPS) administration. Furthermore, rats were given
      GdCl(3) 24 h prior to LPS administration, and survival rate was assessed for 24
      h. Moreover, lung edema was assessed 9 h after LPS injection. Expression of
      inflammatory mediators was measured in the liver and lung. KCs were divided into
      three subpopulations based on size and phagocytosis. The expression of TNF-alpha
      and MIP-2 was greater in the small KCs and lung Muvarphis, while the expression
      of IL-6, IL-10, and MCP-1 was greater in the large and intermediate KCs. GdCl(3)
      eliminated ED2-positive large KCs and did not have any effect on the lung
      Muvarphis. The number of ED1-positive KCs increased significantly in both organs
      after LPS challenge and was reduced by GdCl(3). The population of ED2-positive
      KCs did not change following LPS administration. GdCl(3) completely prevented
      increases in lung microvascular permeability and mortality after LPS infusion.
      After LPS administration, expression of TNF-alpha and IL-6 increased rapidly and
      then decreased gradually in both organs. GdCl(3) inhibited these increases in the
      liver significantly and enhanced the expression of MCP-1 and IL-10 in the lung 9
      h after LPS administration. Thus, the heterogeneous response of KCs to endotoxin
      leads to production of certain cytokines and chemokines that affect lung
      function.

PMID- 16112136
TI  - Morphometry of the amygdala in patients with questionable dementia and mild
      dementia.
AB  - The volume of the amygdala is reduced in advanced Alzheimer's disease (AD).
      However, there is controversy whether amygdala atrophy is present in mild AD and
      in the transitional phase between health and the onset of dementia. The aim of
      this prospective longitudinal study was to investigate whether amygdala atrophy
      is present in subjects with questionable dementia and mild dementia and whether
      amygdala volume is associated with the future rate of cognitive change, that is
      the annual change in the Mini Mental State Examination (MMSE). At baseline,
      volumes of the amygdala were measured in 97 participants aged 70-87 years (40
      controls, 33 patients with questionable dementia, 24 patients with mild AD) using
      magnetic resonance imaging. Eighty-six participants were clinically re-examined
      after 2.3 years on average. At baseline, significant differences in mean amygdala
      volume were found between controls and participants with mild AD. There was no
      significant correlation between the longitudinal annual change in MMSE and the
      baseline amygdala volume in any of the three groups.

PMID- 16112137
TI  - Geometrical correspondence identified and a new interaction unit suggested in
      striated muscle.
AB  - It has long been believed that the periodic structure of the myosin helix is a
      consequence only of compressing the actin-myosin interaction sites. Here, we
      identify a length correspondence between the smallest helical unit on the thick
      filament and the helical pitch of the actin filaments in two different
      contractile muscles. This suggests a rotation/swing of the filaments that creates
      a new interaction unit in addition to the single interaction between an actin
      filament and a myosin head. Numerical characteristics of the single interaction
      are estimated from discussion about an in vivo interaction utilizing the new
      unit. The estimated twisted angle of the actin filaments is consistent with that
      calculated from its torsion rigidity and the evaluated step sizes per cross
      bridge can be performed by a single bend of a myosin head. By comparing our
      evaluated step sizes with experimental results, we conclude that the most
      plausible mechanism at the force-recovery stage involves swings or rotations of
      both filaments in the same direction (clockwise).

PMID- 16112138
TI  - Aging affects oxidative state in hippocampus, hypothalamus and adrenal glands of
      Wistar rats.
AB  - The aging process is associated with cognitive impairment and dysregulation of
      the hypothalamic-pituitary-adrenal (HPA) axis, as well as with oxidative stress.
      We determined some parameters of oxidative stress in homogenates of hippocampus,
      hypothalamus and adrenal glands from male 2-, 6- and 24-months-old Wistar rats. A
      significant age-dependent increase in the generation of free radicals was
      observed in hippocampus, hypothalamus and adrenal glands, as well as on lipid
      peroxidation in hippocampus and hypothalamus. The glutathione peroxidase (GPx)
      activity was significantly reduced in hypothalamus and hippocampus from 6-months
      old rats; a decline on GPx and catalase activities in adrenal glands of 24-months
      old animals was also present. Interestingly, a great decrease in total
      antioxidant capacity was found in all tissues tested. Reported findings support
      the idea that oxidative events participate on multiple neuroendocrine-metabolic
      impairments and suggest that the oxidative stress found in hippocampus,
      hypothalamus and adrenals might be associated with age-related physiological
      deficits.

PMID- 16112139
TI  - Blockade of 5-HT(3) receptor with MDL7222 and Y25130 reduces hydrogen peroxide
      induced neurotoxicity in cultured rat cortical cells.
AB  - The present study was performed to examine the neuroprotective effects of 5
      hydroxytryptamine (5-HT)(3) receptor antagonists against hydrogen peroxide
      (H(2)O(2))-induced neurotoxicity using cultured rat cortical neurons.
      Pretreatment of 5-HT(3) receptor antagonists, tropanyl-3,5-dichlorobenzoate
      (MDL72222, 0.1 and 1 microM) and N-(1-azabicyclo[2.2.2.]oct-3-yl)-6-chloro-4
      ethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide hydrochloride (Y25130,
      0.5 and 5 microM), significantly inhibited the H(2)O(2) (100 microM)-induced
      neuronal cell death as assessed by a MTT assay and the number of apoptotic
      nuclei, evidenced by Hoechst 33342 staining. The protective effects of MDL72222
      (1 microM) and Y25130 (5 microM) were completely blocked by the simultaneous
      treatment with 100 microM 1-phenylbiguanide, a 5-HT(3) receptor agonist,
      indicating that the protective effects of these compounds were due to 5-HT(3)
      receptor blockade. In addition, MDL72222 (1 microM) and Y25130 (5 microM)
      inhibited the H(2)O(2) (100 microM)-induced elevation of cytosolic Ca(2+)
      concentration ([Ca(2+)](c)) and glutamate release, generation of reactive oxygen
      species (ROS), and caspase-3 activity. These results suggest that the activation
      of the 5-HT(3) receptor may be partially involved in H(2)O(2)-induced
      neurotoxicity, by membrane depolarization for Ca(2+) influx. Therefore, the
      blockade of 5-HT(3) receptor with MDL72222 and Y25130 may ameliorate the H(2)O(2)
      induced neurotoxicity by interfering with the increase of [Ca(2+)](c), and then
      by inhibiting glutamate release, generation of ROS and caspase-3 activity.

PMID- 16112140
TI  - Photodegradation products of propranolol: the structures and pharmacological
      studies.
AB  - Recently, single-dose drug packaging systems, allowing the administration of
      multiple drugs in a single pill, have become popular for the convenience of the
      patient. The quality of drugs and an accurate measurement of their
      photostabilities within this system, however, have not been carefully addressed.
      Drugs that are unstable in light should be carefully handled to protect their
      potency and ensure their safety. Propranolol (1), a beta-adrenergic receptor
      antagonist, is widely used for angina pectoris, arrhythmia, and hypertension. Due
      to its naphthalene skeleton, this drug may be both light unstable and a
      photosensitizing agent. In this study, we isolated three photodegraded products
      of propranolol (1): 1-naphthol (2), N-acetylpropranolol (3), and N
      formylpropranolol (4). The structures of these compounds were determined by
      spectroscopic methods and chemical syntheses. We also examined the acute
      toxicities of these substances in mice and their binding to beta-adrenergic
      receptors using rat cerebellum cortex membranes. Although the photoproducts
      isolated in this study did not exhibit any acute toxicity or significant binding
      to beta-adrenergic receptors, these results serve as a warning to single-dose
      packaging systems, as propranolol (1) must be handled carefully to protect the
      compound from light-induced degradation.

PMID- 16112141
TI  - Baseline study of perfluorooctane sulfonate occurrence in mussels, Mytilus
      galloprovincialis, from north-central Portuguese estuaries.

PMID- 16112142
TI  - Synthetic musks-arising new environmental menace?

PMID- 16112143
TI  - Prior exposure to Cu contamination influences the outcome of toxicological
      testing of Fucus serratus embryos.
AB  - Brown seaweeds are often employed in single species toxicity testing to study the
      association between the pollutant and the biota in contaminated marine habitats.
      We have used Fucus serratus (Phaeophyta) from one Cu resistant and one non
      resistant population to evaluate the effect of prior exposure to metal pollution
      on toxicological endpoints. Analysis of comparative toxicity was conducted for
      embryo rhizoid elongation and adult relative growth rate (RGR). Algae that had
      previously been exposed to Cu expressed consistently lower levels of sensitivity
      to Cu than those that had no history of exposure to the pollutant. For both non
      resistant and resistant populations rhizoid length was a more sensitive endpoint
      than adult RGR. While early life history stages of brown algae are generally
      regarded as being pollution-sensitive and inhibition of spore and embryo rhizoid
      elongation is frequently used as endpoints in bioassays, the test results may be
      affected by prior exposure of the parent algae to the pollutant. We conclude that
      the effect of prior exposure should be considered when comparing endpoints
      between studies and when selecting material for future testing.

PMID- 16112144
TI  - Status of butyltin pollution along the coasts of western Japan in 2001, 11 years
      after partial restrictions on the usage of tributyltin.
AB  - Restrictions on the use of tributyltin (TBT) in aquaculture and on boats in
      coastal regions, except for ocean-going vessels, have been in place in Japan
      since 1990 due to the strong toxic effects of TBT on marine organisms. However,
      TBT pollution along the Japanese coasts has been reported after this legislation
      was enacted. In order to elucidate the present status of contamination by
      butyltin (BT) compounds, we measured the levels of BTs [monobutyltin (MBT),
      dibutyltin (DBT) and TBT] in seawater and Caprella spp. samples obtained from the
      western part of Seto Inland Sea, Uwa Sea and Uranouchi Bay in western Japan
      during March to September, 2001. Butyltins were detected in more than 90% of the
      seawater samples (n = 59), with average concentrations of 8.2+/-9.2 (SD) ng MBT
      L(-1), 3.3+/-3.0 ng DBT L(-1) and 9.0+/-7.0 ng TBT L(-1). Among 41 stations
      situated on coastal lines, a sufficient number of Caprella organisms for chemical
      analysis could be collected from only 16 stations. The butyltin concentrations in
      seawater and Caprella samples from Uwa Sea and Uranouchi Bay, in which the
      dominant industry in both waters is aquaculture, showed significantly higher than
      or no significant differences from those samples from the western part of Seto
      Inland Sea, a major heavy-industry area in Japan. As the TBT concentration in
      seawater increased, the number of Caprella organisms collected decreased. The
      mean TBT concentration among the seawater samples was above the estimated lowest
      observable effect concentration (LOEC) that reduces the survival rate of Caprella
      danilevskii. Thus, the present study indicates that TBT is still a potential
      ecological hazard to the survival of marine invertebrates inhabiting coasts along
      western Japan, even 11 years after the partial ban on TBT usage was implemented.

PMID- 16112145
TI  - Acidosis in muscle tissue distal to vascular contusion despite unchanged global
      blood flow in rats: an uncoupling of microvascular blood flow and metabolism?
AB  - Studies using a contusion trauma model have shown that the femoral artery of the
      rat remains patent in 85% despite a severe vessel injury. A significant increase
      in tissue oxygenation (PtO2) has been found despite only a minor effect on blood
      flow (<20% decrease) on the muscle surface distal to the injury indicating a
      disturbed relationship between microvascular blood flow and metabolism. The aim
      of the present study was to further study the interplay between microvascular
      blood flow and metabolism within the distal muscle using an ethanol clearance
      technique (blood flow) in conjunction to the determination of an ischemia marker
      (lactate) by use of microdialysis. Although skeletal muscle blood flow remained
      unaltered as assessed by ethanol clearance, skeletal muscle lactate levels
      increased significantly (P<0.001) post-trauma in both legs. The increase was
      initially higher, faster and the increase over time larger in the trauma leg as
      compared to the control leg (P<0.001). These findings indicate a systemic effect
      of the trauma. Further, it suggests a functional impairment of the relationship
      between microvascular blood flow and/or muscle metabolic processes when the
      trauma is directed towards the supplying blood vessel. The reason for this
      anaerobic insult as found in this study compared to the presence of a local
      increase in PtO2 in the trauma leg as shown in our previous study is suggestive
      of an microvascular blood flow and tissue metabolism uncoupling.

PMID- 16112146
TI  - Biomarkers in risk assessment of asbestos exposure.
AB  - Developments in the field of molecular epidemiology and toxicology have given
      valuable tools for early detection of impending disease or toxic condition.
      Morbidity due to respiratory distress, which may be due to environmental and
      occupational exposure, has drawn attention of researchers worldwide. Among the
      occupational exposure to respiratory distress factors, fibers and particles have
      been found to be main culprits in causing diseases like asbestosis, pleural
      plaques, mesotheliomas and bronchogenic carcinomas. An early detection of the
      magnitude of exposure or its' effect using molecular end points is of growing
      importance. The early inflammatory responses like release of the inflammatory
      cells collected by non-invasive methods give an indication of the unwanted
      exposure and susceptibility to further complications. Since free radicals like O2
      , OH, OOH, NO, NOO, etc. are involved in the progression of asbestos-related
      diseases and lead to cytogenetic changes, an evaluation of antioxidant states
      reducing equivalents like GSH and ROS generation can be a good biomarker. The
      cytogenetic end points like chromosomal aberration, micronucleus formation and
      sister chromatid exchange give indication of genetic damage, hence they are used
      as effective biomarkers. New techniques like fluorimetric analysis of DNA
      unwinding, alkaline elution test, fluorescent in situ hybridization and comet
      assay are powerful tools for early detection of initiation of disease process and
      may help in planning strategies for minimizing morbidity related to asbestos
      fiber exposure. The present review article covers in detail possible biomarkers
      for risk assessment of morbidity due to fibers/particles in exposed population.

PMID- 16112147
TI  - What does recovery from anomia tell us about the underlying impairment: the case
      of similar anomic patterns and different recovery.
AB  - Although word-finding difficulties have been largely studied from a theoretical
      and a rehabilitation point of view, recovery mechanisms and especially the fact
      that patients with similar anomic patterns may exhibit different recovery, are
      still not fully understood. In the first part of the present study we
      investigated the word retrieval curve during therapy and the psycholinguistic
      variables affecting word-finding recovery patterns in three anomic subjects (PG,
      AH and TM). Despite the fact that all patients had similar anomia at baseline,
      they presented different recovery patterns during an identical therapy program.
      The progress during therapy and the number of sessions necessary to reach
      satisfactory improvement was similar in two patients (AH and TM), but differed in
      the third patient (PG), who needed more treatment sessions. Moreover, these two
      different patterns were affected by different psycholinguistic variables: words
      age of acquisition predicted improvement in AH and TM, whereas phonological
      neighbourhood predicted improvement in PG. Following the observation that
      phonological neighbourhood density affected the slower progress during therapy,
      in the second study we analysed whether this variable also predicts pseudo-word
      learning in healthy controls and in anomic subjects. Indeed, phonological
      neighbourhood predicted pseudo-word learning speed in controls and in some anomic
      patients. We suggest that the analysis of progress during therapy for anomia and
      the comparison of the variables affecting learning and recovery may provide
      information about the underlying nature of the anomic deficit that is not
      available through the simple assessment of performance.

PMID- 16112148
TI  - Differential role of the orbital frontal lobe in emotional versus cognitive
      perspective-taking.
AB  - Lesions of the orbital frontal lobe, particularly its medial sectors, are known
      to cause deficits in empathic ability, whereas the role of this region in theory
      of mind processing is the subject of some controversy. In a functional magnetic
      resonance imaging study with healthy participants, emotional perspective-taking
      was contrasted with cognitive perspective-taking in order to examine the role of
      the orbital frontal lobe in subcomponents of theory of mind processing. Subjects
      responded to a series of scenarios presented visually in three conditions:
      emotional perspective-taking, cognitive perspective-taking and a control
      condition that required inferential reasoning, but not perspective-taking. Group
      results demonstrated that the medial orbitofrontal lobe, defined as Brodmann's
      areas 11 and 25, was preferentially involved in emotional as compared to
      cognitive perspective-taking. This finding is both consistent with the lesion
      literature, and resolves the inconsistency of orbital frontal findings in the
      theory of mind literature.

PMID- 16112149
TI  - Opposite effect of negative and positive affect on stress procoagulant
      reactivity.
AB  - Exaggerated procoagulant responses to acute mental stress may contribute to
      coronary thrombosis, and continuing low-grade systemic coagulation activation may
      link negative affect with the development of coronary artery disease. We
      investigated whether negative and positive affect and perceived social support
      would moderate stress procoagulant reactivity. Psychological functioning,
      exhaustion, negative affectivity, depression, anxiety, worrying, vigor, and
      social support were assessed in 27 apparently healthy men (mean age 47 +/- 8
      years) who underwent the 13-min Trier Social Stress Test combining preparation,
      speech, and mental arithmetic. Plasma levels of von Willebrand factor antigen
      (VWF:Ag), fibrinogen, factor VII clotting activity (FVII:C), FVIII:C, FXII:C, and
      D-dimer were measured immediately before and after stress. Acute stress elicited
      significant increases in hemodynamic, cortisol, and coagulant activity (p values
      < 0.05). VWF:Ag reactivity showed inverse relationships with exhaustion (r = 
      0.63, p < 0.001), negative affectivity (r = -0.53, p = 0.005), and worrying (r = 
      0.53, p = 0.005). Exhaustion and negative affectivity emerged as independent
      predictors of VWF:Ag reactivity explaining 54% of its variance. Fibrinogen
      reactivity showed inverse relationships with negative affectivity (r = -0.59, p =
      0.002) and anxiety (r = -0.54, p = 0.005); negative affectivity emerged as an
      independent predictor of fibrinogen reactivity explaining 35% of its variance.
      Psychological functioning and FVII:C reactivity were also correlated (r = -0.52,
      p = 0.006). Whereas FVIII:C reactivity correlated positively with vigorous mood
      (r = 0.48, p = 0.012), positive associations between social support and
      procoagulant reactivity did not reach significance. Negative affect was
      associated with attenuated procoagulant reactivity to stress and the opposite was
      observed for positive affect. Negative affect is not likely to enhance the acute
      procoagulant stress response in healthy men.

PMID- 16112150
TI  - Effects of harmaline on anxiety-related behavior in mice.
AB  - Harmaline (HA) is a beta-carboline commonly known to provoke motor alterations
      through activation of cells in the inferior olive. In addition, this
      pharmacological agent also induces cognitive disturbances such as motor and
      spatial learning impairments. In order to complete and extend these data, we
      examined the effects of this drug on state anxiety in mice, employing elevated
      plus maze test. We report here that lower doses of harmaline (5-10 mg/kg) have
      anxiogenic since higher doses (20 mg/kg) have anxiolytic-like properties. Overall
      pattern of our behavioral results provides evidence that harmaline also acts on
      emotional reactivity in mice by influencing their decision making when placed in
      an anxiogenic situation.

PMID- 16112151
TI  - Corticosteroids as potential mechanism regulating variability in reproductive
      success in monogamous oldfield mice (Peromyscus polionotus).
AB  - Male and female mammals undergo profound hormonal changes during pregnancy, some
      of which are sufficiently dramatic to influence offspring survival. In order to
      understand the proximate mechanisms regulating the variability in reproductive
      success within and between individuals, we monitored changes in fecal
      corticosteroid concentrations over the reproductive cycle in male and female
      oldfield mice (Peromyscus polionotus subgriseus) to test whether corticosteroid
      concentrations during pregnancy were associated with offspring survival. In
      females that successfully raised litters to weaning, fecal corticosteroid
      concentrations were low until mid-gestation and increased significantly towards
      term; in females that did not raise their pups to weaning, fecal corticosteroid
      concentrations were significantly higher at mid-gestation, and remained high
      until late gestation. The difference in fecal corticosteroid concentrations at
      mid-gestation between successful and unsuccessful females can be explained by the
      fact that successful females were lactating. Lactation has been associated with a
      down-regulation of the hypothalamic-pituitary-adrenal (HPA) axis and,
      accordingly, a decrease in plasma corticosterone (CORT) in several species,
      including humans. Males that successfully raised their litters had low fecal
      corticosteroid concentrations throughout their partner's pregnancy. Unsuccessful
      males, however, had significantly higher fecal corticosteroid concentrations at
      term than males that raised their pups to weaning. While these preliminary data
      require further investigation, we suggest that pre-partum fecal corticosteroid
      concentrations in males were responsible for the variability in reproductive
      success.

PMID- 16112152
TI  - Relating particles and texture perception.
AB  - Practically all foods contain particles. It has been suggested that the presence
      of particles in food may affect the perception of sensory attributes. In the
      present study we investigated the effect of size and type (hardness and shape) of
      particles added to a CMC based vanilla custard dessert. The two types of
      particles included in the study were silica dioxide and polystyrene spheres,
      varying in size from 2 to 230 microm. Eighteen trained adults participated in the
      study. They rated the sensation of 17 sensory flavour and texture attributes on a
      100-point visual analogue scale (VAS). The results indicate that the addition of
      particles increased the sensation of roughness attributes and decreased the
      ratings of a number of presumably favorable texture attributes (smoothness,
      creamy, fatty and slippery) significantly. These effects increased with
      increasing particle size up to 80 microm. Roughness ratings deceased for larger
      particles sizes. Surprisingly, even particles of 2 microm had significant
      effects: they increased perceived rough lip-tooth feel, and decreased slippery
      lip-tooth feel and smoothness of the product. The affected attributes had
      previously been related to lubricative properties of foods. Particles added to
      semi-solid foods with relatively low levels of fat seem to counteract the
      lubricating effects of the fat resulting in increased oral friction. In a
      separate study on size perception the silica dioxide particles were used. By
      sampling the stimuli between the tongue and palate, subjects rated the size of
      the particles on a 100-point scale in comparison to anchor stimuli containing no
      particles and particles of 250 microm. The perceived particle size significantly
      increased for larger particles. Furthermore, perceived particle size was
      negatively correlated with roughness ratings. Thus, subjects who were sensitive
      and perceived the particles as being relatively large reported the same stimuli
      to have less rough after-feel. In conclusion, particles added to a product induce
      large effects on texture sensations, and texture sensation is related to
      individual size perception.

PMID- 16112153
TI  - Removal of the N-linked glycan structure from the peanut peroxidase prxPNC2:
      influence on protein stability and activity.
AB  - Lines of transgenic tobacco have been generated that are transformed with either
      the wild-type peanut peroxidase prxPNC2 cDNA, driven by the CaMV35S promoter
      (designated 35S::prxPNC2-WT) or a mutated PNC2 cDNA in which the asparagine
      residue (Asn189) associated with the point of glycan attachment (Asn189) has been
      replaced with alanine (designated 35S::prxPNC2-M). PCR, using genomic DNA as
      template, has confirmed the integration of the 35S::prxPNC2-WT and 35S:prxPNC2-M
      constructs into the tobacco genome, and western analysis using anti-PNC2
      antibodies has revealed that the prxPNC2-WT protein product (PNC2-WT) accumulates
      with a molecular mass of 34,670 Da, while the prxPNC2-M protein product (PNC2-M)
      accumulates with a molecular mass of 32,600 Da. Activity assays have shown that
      both PNC2-WT and PNC2-M proteins accumulate preferentially in the ionically-bound
      cell wall fraction, with a significantly higher relative accumulation of the PNC2
      WT isoenzyme in the ionically-bound fraction when compared with the PNC2-M
      isoform. Kinetic analysis of the partially purified PNC2-WT isozyme revealed an
      affinity constant (apparent Km) of 11.2 mM for the reductor substrate guaiacol
      and 1.29 mM for H2O2, while values of 11.9 mM and 1.12 mM were determined for the
      PNC2-M isozyme. A higher Arrenhius activation energy (Ea) was determined for the
      PNC2-M isozyme (22.9 kJ mol(-1)), when compared with the PNC2-WT isozyme (17.6 kJ
      mol(-1)), and enzyme assays have determined that the absence of the glycan
      influences the thermostability of the PNC2-M isozyme. These results are discussed
      with respect to the proposed roles of N-linked glycans attached to plant
      peroxidases.

PMID- 16112154
TI  - Epidemiology of malaria in Attapeu Province, Lao PDR in relation to entomological
      parameters.
AB  - Surveys were conducted in malaria-endemic villages in the southern province of
      Attapeu, Lao PDR during various seasons over a 3-year period. All-night mosquito
      landing collections, blood surveys and a case-control study were conducted.
      Plasmodium falciparum was the predominant species, and slide positivity rates
      were higher during the transition/dry season compared with the wet season.
      Anopheles dirus A was found to be the primary vector, and sporozoite rates were
      highest during the transition/dry season. Anopheles dirus was found to be
      endophagic and endophilic. Not using insecticide-treated bed nets, houses close
      to breeding sites and sleeping away from home were risk factors associated with
      malaria.

PMID- 16112155
TI  - Molecular mechanisms underlying mancozeb-induced inhibition of TNF-alpha
      production.
AB  - Mancozeb, a polymeric complex of manganese ethylenebisdithiocarbamate with zinc
      salt, is widely used in agriculture as fungicide. Literature data indicate that
      ethylenebisdithiocarbamates (EBDTCs) may have immunomodulatory effects in humans.
      We have recently found in agricultural workers occupationally exposed to the
      fungicide mancozeb a statistically significant decrease in lipopolysaccharide
      (LPS)-induced tumor necrosis factor-alpha (TNF) production in leukocytes. TNF is
      an essential proinflammatory cytokine whose production is normally stimulated
      during an infection. The purpose of this work was to establish an in vitro model
      reflecting in vivo data and to characterize the molecular mechanism of action of
      mancozeb. The human promyelocytic cell line THP-1 was used as in vitro model to
      study the effects of mancozeb and its main metabolite ethylenthiourea (ETU) on
      LPS-induced TNF release. Mancozeb, but not ETU, at non-cytotoxic concentrations
      (1-100 microg/ml), induced a dose- and time-dependent inhibition of LPS-induced
      TNF release, reflecting in vivo data. The modulatory effect observed was not
      limited to mancozeb but also other EBDTCs, namely zineb and ziram, showed similar
      inhibitory effects. Mancozeb must be added before or simultaneously to LPS in
      order to observe the effect, indicating that it acts on early events triggered by
      LPS. It is known that nuclear factor-kappaB (NF-kappaB) tightly regulates TNF
      transcription. We could demonstrate that mancozeb, modulating LPS-induced
      reactive oxygen species generation, prevented IkappaB degradation and NF-kappaB
      nuclear translocation, which in turn resulted in decreased TNF production. To
      further understand the mechanism of the effect of mancozeb on TNF transcription,
      THP-1 cells were transfected with NF-kappaB promoter-luciferase construct, and
      the effect of mancozeb on luciferase activity was measured. Cells transfected
      with promoter constructs containing kappaB site showed decreased LPS-induced
      luciferase activity relative to control after mancozeb treatment, confirming NF
      kappaB binding as an intracellular target of mancozeb. Overall, this study
      contributes to our understanding of the mechanism underlying mancozeb-induced
      immunotoxicity.

PMID- 16112157
TI  - In vivo assessment of toxicity and pharmacokinetics of methylglyoxal.
      Augmentation of the curative effect of methylglyoxal on cancer-bearing mice by
      ascorbic acid and creatine.
AB  - Previous in vivo studies from several laboratories had shown remarkable curative
      effect of methylglyoxal on cancer-bearing animals. In contrast, most of the
      recent in vitro studies have assigned a toxic role for methylglyoxal. The present
      study was initiated with the objective to resolve whether methylglyoxal is truly
      toxic in vivo and to reassess its therapeutic potential. Four species of animals,
      both rodent and non-rodent, were treated with different doses of methylglyoxal
      through oral, subcutaneous and intravenous routes. Acute (treatment for only 1
      day) toxicity tests had been done with mouse and rat. These animals received 2, 1
      and 0.3 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous
      and intravenous routes respectively. Chronic (treatment for around a month)
      toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog
      received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through
      oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3
      and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous
      and intravenous routes respectively. It had been observed that methylglyoxal had
      no deleterious effect on the physical and behavioral pattern of the treated
      animals. Fertility and teratogenecity studies were done with rats that were
      subjected to chronic toxicity tests. It had been observed that these animals
      produced healthy litters indicating no damage of the reproductive systems as well
      as no deleterious effect on the offspring. Studies on several biochemical and
      hematological parameters of methylglyoxal-treated rats and dogs and histological
      studies of several organs of methylglyoxal-treated mouse were performed. These
      studies indicated that methylglyoxal had no apparent deleterious effect on some
      vital organs of these animals. A detailed pharmacokinetic study was done with
      mouse after oral administration of methylglyoxal. The effect of methylglyoxal
      alone and in combination with creatine and ascorbic acid on cancer-bearing
      animals had been investigated by measuring the increase in life span and tumor
      cell growth inhibition. The results indicated that anticancer effect of
      methylglyoxal was significantly augmented by ascorbic acid and further augmented
      by ascorbic acid and creatine. Nearly 80% of the animals treated with
      methylglyoxal plus ascorbic acid plus creatine were completely cured and devoid
      of any malignant cells within the peritoneal cavity.

PMID- 16112156
TI  - Protective and detrimental effects of kaempferol in rat H4IIE cells: implication
      of oxidative stress and apoptosis.
AB  - Flavonoids are ubiquitous substances in fruits and vegetables. Among them, the
      flavonol kaempferol contributes up to 30% of total dietary flavonoid intake.
      Flavonoids are assumed to exert beneficial effects on human health, e.g.,
      anticancer properties. For this reason, they are used in food supplements at high
      doses. The aim of this project was to determine the effects of kaempferol on
      oxidative stress and apoptosis in H4IIE rat hepatoma cells over a broad
      concentration range. Kaempferol is rapidly taken up and glucuronidated by H4IIE
      cells. The results demonstrate that kaempferol protects against H2O2-induced
      cellular damage at concentrations which lead to cell death and DNA strand breaks
      in the absence of H2O2-mediated oxidative stress. Preincubation with 50 microM
      kaempferol exerts protection against the loss of cell viability induced by 500
      microM H2O2 (2 h) while the same concentration of kaempferol reduces cell
      viability by 50% in the absence of H2O2 (24 h). Preincubation with 50 microM
      kaempferol ameliorates the strong DNA damage induced by 500 microM H2O2 while 50
      microM kaempferol leads to a significant increase of DNA breakage in the absence
      of H2O2. Preincubation with 50 microM kaempferol reduces H2O2-mediated caspase-3
      activity by 40% (4 h) while the same concentration of kaempferol leads to the
      formation of a DNA ladder in the absence of H2O2 (24 h). It is concluded that the
      intake of high dose kaempferol in food supplements may not be advisable because
      in our cellular model protective kaempferol concentrations can also induce DNA
      damage and apoptosis by themselves.

PMID- 16112158
TI  - HPLC determination of free nitrogenous compounds of Centaurea solstitialis
      (Asteraceae), the cause of equine nigropallidal encephalomalacia.
AB  - Centaurea solstitialis (yellow star thistle) has been proven to cause equine
      nigropallidal encephalomalacia in horses. Over the last fifty years,
      nigropallidal encephalomalacia has been of interest to human medicine due to the
      possible connection with Parkinson's disease. Previous studies indicated the
      presence of neurotoxic nitrogenous compounds in polar extracts of the plant. In
      order to give a more detailed description of the nitrogen-containing fraction of
      C. solstitialis, various samples were collected at different development stages.
      Different aliquots of the same aqueous extract were directly derivatized with o
      phthaldialdehyde and dansyl chloride and analyzed separately by reversed-phase
      HPLC. A complete profile of the free nitrogenous fraction of C. solstitialis was
      given and results obtained with the two derivatization procedures were compared.
      No particularly high level of free aspartic and glutamic acids, two potent
      neuroexcitotoxic amino acids, were found in polar extracts of the plant. Tyramine
      resulted to be the most important biologically active amine present in C.
      solstitialis (with a mean concentration of 2.0 mg/100 g of dry weight).

PMID- 16112159
TI  - The tubule-forming NSm protein from Tomato spotted wilt virus complements cell-to
      cell and long-distance movement of Tobacco mosaic virus hybrids.
AB  - A Florida isolate of Tomato spotted wilt virus (TSWV) was able to complement cell
      to-cell movement of a movement-defective Tobacco mosaic virus (TMV) vector
      expressing the jellyfish green fluorescent protein (GFP). To test for
      complementation of movement in the absence of other TSWV proteins, the open
      reading frame for the NSm protein was expressed from TMV constructs encoding only
      the TMV replicase proteins. NSm was expressed from either the coat protein or
      movement protein subgenomic promoter, creating virus hybrids that moved cell to
      cell in inoculated leaves of tobacco, providing the first functional
      demonstration that NSm is the TSWV movement protein. Furthermore, these CP
      deficient hybrids moved into upper leaves of Nicotiana benthamiana, demonstrating
      that NSm can support long-distance movement of viral RNAs. Tubules,
      characteristic of the NSm protein, were also formed in tobacco protoplasts
      infected with the TMV-TSWV hybrids. The C-terminus of the NSm protein was shown
      to be required for movement. TMV-TSWV hybrids expressing NSm and GFP moved within
      inoculated leaves. Our combination of single-cell and intact plant experiments to
      examine multiple functions of a heterologous viral protein provides a generalized
      strategy with wider application to other viruses also lacking a reverse genetic
      system.

PMID- 16112160
TI  - Genetic rearrangements on the Chlorovirus genome that switch between hyaluronan
      synthesis and chitin synthesis.
AB  - Chlorella viruses or chloroviruses form polysaccharide fibers on the cell wall of
      host Chlorella cells after infection. Such polysaccharides are either hyaluronan
      synthesized by virus-encoded hyaluronan synthase (HAS) or chitin synthesized by
      viral chitin synthase (CHS). Some chloroviruses synthesize both hyaluronan (HA)
      and chitin simultaneously. To understand the relationship between "HA
      synthesizing" and "chitin-synthesizing" viruses, we characterized the CVK2
      genomic regions, one flanking chs and the other corresponding to PBCV-1 has and
      found that on CVK2 DNA, a single ORF (PBCV-1 A330R) was replaced with a 5 kbp
      region containing chs, ugdh2 (the second gene for UDP-glucose dehydrogenase) and
      two other ORFs, and that has was replaced with another chs gene. In some
      chloroviruses, ugdh was lost. These results suggest that chlorovirus types
      changed from "has viruses" to "chs viruses" or from "chs viruses" to "has
      viruses" by exchanging the genes.

PMID- 16112161
TI  - LH3, a "homologue" of the mastadenoviral E1B 55-kDa protein is a structural
      protein of atadenoviruses.
AB  - Ovine adenovirus serotype 7 (OAdV), the prototype atadenovirus, has gene
      homologues for most mastadenovirus structural proteins but lacks proteins V and
      IX. Instead, OAdV has structural proteins of 32 and 42 kDa although the gene
      encoding the latter had not previously been identified. The presently reported
      studies of OAdV virions have now identified a minor structural polypeptide of
      approximately 40 kDa as the product of the L1 52/55-kDa gene and, more
      surprisingly, shown that the 42-kDa protein is encoded by LH3. This gene product
      was previously thought to be a homologue of mastadenovirus E1B 55 kDa, which is a
      multi-functional, non-structural protein that cooperates with E1A in cell
      transformation. The lack of transforming activity previously demonstrated for
      OAdV combined with a structural role for the LH3 product indicates that the
      protein has a different function in atadenoviruses. We discuss the abundance and
      likely core location of LH3 in the virion and the possible derivation of the E1B
      55-kDa gene from the LH3 gene.

PMID- 16112162
TI  - Contribution of trace metals from atmospheric deposition to stormwater runoff in
      a small impervious urban catchment.
AB  - The contribution of atmospheric deposition to emissions of trace metals in
      stormwater runoff was investigated by quantifying wet and dry deposition fluxes
      and stormwater discharges within a small, highly impervious urban catchment in
      Los Angeles. At the beginning of the dry season in spring 2003, dry deposition
      measurements of chromium, copper, lead, nickel, and zinc were made monthly for 1
      year. Stormwater runoff and wet deposition samples also were collected, and
      loading estimates of total annual deposition (wet+dry) were compared with annual
      stormwater loads. Wet deposition contributed 1-10% of the total deposition inside
      the catchment, indicating the dominance of dry deposition in semi-arid regions
      such as Los Angeles. Based on the ratio of total deposition to stormwater,
      atmospheric deposition potentially accounted for as much as 57-100% of the total
      trace metal loads in stormwater within the study area. Despite potential bias
      attributable to processes that were not quantified in this study (e.g.,
      resuspension out of the catchment or sequestration within the catchment), these
      results demonstrate atmospheric deposition represents an important source of
      trace metals in stormwater to waterbodies near urban centers.

PMID- 16112163
TI  - Comment on "Test for assessing shear sensitivity of activated sludge flocs: a
      feasibility study" by M.A. Seka and W. Verstraete [Wat. Res. 37, 3327-3334
      (2003)].

PMID- 16112164
TI  - Evaluation of an MBR-RO system to produce high quality reuse water: microbial
      control, DBP formation and nitrate.
AB  - A membrane bioreactor and reverse osmosis (MBR-RO) system was developed to assess
      potential reuse applications of municipal wastewater. The objective of the study
      was to examine the water quality throughout the system with a focus on waterborne
      pathogens, disinfection by-products (DBPs) and nitrate. This paper will discuss
      the presence of these contaminants in MBR effluent and focus on their subsequent
      removal by RO. This study has shown that high quality reuse water can be produced
      from municipal wastewater through the use of an MBR-RO system. The water meets
      California Title 22 reuse regulations for non-potable applications and US EPA
      drinking water limits for trihalomethanes (THM) (80 microg/L), haloacetic acids
      (HAA) (60 microg/L), chlorite (1.0 mg/L), total coliform (not detectable),
      viruses (not detectable), and nitrate/nitrite (10 mg N/L). However, THM formation
      (182-689 microg/L) attributed to cleaning of the MBR with chlorine and incomplete
      removal by subsequent RO treatment resulted in reuse water with THM levels
      (40.2+/-19.9 microg/L) high enough to present a potential concern when
      considering drinking water applications. Nitrate levels of up to 3.6 mg N/L,
      which resulted from incomplete removal by the RO membrane, are also a potential
      concern. A denitrification step in the MBR should be considered in potable water
      applications.

PMID- 16112165
TI  - Coagulation of humic substances and dissolved organic matter with a ferric salt:
      an electron energy loss spectroscopy investigation.
AB  - Transmission electron microscopy (TEM) coupled with electron energy loss
      spectroscopy (EELS) and energy dispersive X-ray spectroscopy (EDXS) was used to
      investigate the coagulation of natural organic matter with a ferric salt. Jar
      test experiments were first conducted with a reconstituted water containing
      either synthetic or natural extracts of humic substances, and then with a raw
      water from Moselle River (France). The characterization of the freeze-dried
      coagulated sediment by EELS in the 250-450 eV range, showed that Fe-coagulant
      species predominantly associate with the carboxylic groups of organic matter, and
      that this interaction is accompanied by a release of previously complexed calcium
      ions. The variation of Fe/C elemental ratio with iron concentration provides
      insightful information into the coagulation mechanism of humic substances. At
      acid pH, Fe/C remains close to 3 over the whole range of iron concentrations
      investigated, while a much lower atomic ratio is expected from the value of
      optimal coagulant dosage. This suggests that a charge neutralization/complexation
      mechanism is responsible for the removal of humic colloids, the aggregates being
      formed with both iron-coagulated and proton-neutralized organic compounds. At pH
      8, the decrease in Fe/C around optimal coagulant concentration is interpreted as
      a bridging of stretched humic macromolecules by Fe-hydrolyzed species.
      Aggregation would then result from a competition between reconformation of humic
      chains around coagulant species and collision of destabilized humic material.
      EELS also enabled a fingerpriting of natural organic substances contained in the
      iron-coagulated surface water, N/C elemental analyses revealing that humic
      colloids are removed prior to proteinic compounds.

PMID- 16112166
TI  - A study on volatile organic sulfide causes of odors at Philadelphia's Northeast
      Water Pollution Control Plant.
AB  - Volatile organic sulfide (VOS) causes of odors were studied at Philadelphia's
      Northeast Water Pollution Control Plant between September 11 and November 25,
      2003. Results showed that dimethyl sulfide (DMS) dominated the VOS pool whenever
      VOS concentration rose above the background level (<50 microg/L). Methanethiol
      was generally less than 10% of VOS and it was mainly found at sites with limited
      or reduced dissolved oxygen (DO). Dimethyl disulfide occupied approximately 1% of
      the VOS and was often not detectable. Carbon disulfide was not detected. The
      concentrations of DMS varied by three orders of magnitude, ranging from <5 to
      1260 microg/L. High concentrations of DMS, averaging 419 and ranging from <5 to
      1000 microg/L, were generally found in return activated sludge. The DMS
      concentration in the primary effluent ranged from <5 to 729 microg/L and averaged
      245 microg/L. Concentrations of DMS in the aeration tank (AT) with high DO were
      from <5 to 997 microg/L with an average of 250 microg/L. However, DMS
      concentrations in the AT representing anaerobic conditions were as high as 1260
      microg/L. The estimated average purge efficiency of DMS was about 78%, which
      required a DMS production rate of 108 microg/Lh(-1) to keep the analyzed
      concentration in the AT. While a valid but weak statistical relationship between
      acetone and DMS was observed, there was no strong evidence to support that the
      methylation of hydrogen sulfide with acetone could be the mechanism for the DMS
      formation. Instead, DMS production was found to be associated with the
      characteristics of incoming wastewater. Thus, a VOS precursor was believed to be
      present in the incoming wastewater, which warranted a need for further
      investigation.

PMID- 16112167
TI  - Rapid quantification of bacteria in activated sludge using fluorescence in situ
      hybridization and epifluorescence microscopy.
AB  - A rapid quantification method for bacteria in activated sludge has been
      developed, based on fluorescence in situ hybridization (FISH) and epifluorescence
      microscopy. Samples are hybridized on slides and analyzed by direct microscopic
      observation. Abundance categories were designed based on digital images of the
      target organisms. These rating systems were developed for the filamentous
      bacteria Microthrix parvicella and for different morphotypes of nocardioform
      actinomycetes, but can easily be adapted to other types of microorganisms. Due to
      the quantification by direct microscopic observation, this method is suitable for
      samples that are difficult to be processed by semi-automated image analysis
      techniques, such as samples containing fluorescent debris, cells of different
      fluorescence intensities and target organisms that need partial enzymatic
      digestion prior to FISH. In contrast to commonly used rating systems consisting
      of photographs, the newly developed categories allow to quantitatively compare
      results of different categories and different organisms. The uncertainties of the
      results were calculated by a non-parametric bootstrap procedure; a thorough
      uncertainty analysis was performed including sample variability and operator
      subjectivity.

PMID- 16112168
TI  - Evaluation of water treatment sludges toxicity using the Daphnia bioassay.
AB  - Alum and ferric chloride sludges from two water treatment plants (WTPs) were
      analyzed regarding their physicochemical characteristics and toxicity to Daphnia
      similis. Experiments were carried out in the dry and rainy seasons. Acute and
      chronic toxicity was measured using survival and reproduction as measurement
      endpoints. No acute toxicity of the sludge was observed in 48 h exposure. Ferric
      chloride sludge caused chronic toxicity, demonstrated by low fecundity and some
      mortality, while alum sludge caused chronic toxicity characterized by low
      fecundity. Some sludge characteristics varied between samplings, including
      turbidity, solids contents, N, P and metal (Al and Fe) concentrations. These
      variables and the increase of chemical oxygen demand (COD) were identified as the
      main cause of degradation of the receiving waters. However, no relationship was
      observed between these variables and degree of toxicity. It is apparent from
      these results that water treatment sludges may be toxic and therefore may impair
      receiving waters. Alum sludge was less toxic than ferric chloride sludge.

PMID- 16112169
TI  - Mechanisms of lead biosorption on cellulose/chitin beads.
AB  - Environment-friendly cellulose/chitin beads being prepared by coagulating a blend
      of cellulose and chitin in 6 wt% NaOH/5 wt% thiourea aqueous solution with 5%
      H2SO4 possessed higher heavy metals uptake capacity than pure chitin flakes. The
      mechanisms of Pb2+ adsorption on cellulose/chitin beads at pH0=5 were
      investigated at the molecular levels by scanning electron micrographs (SEM),
      transmission electron micrographs (TEM), X-ray photoelectron spectroscopy (XPS),
      Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction
      (XRD). The result revealed that mechanisms for the adsorption of Pb2+ on the
      cellulose/chitin beads could be described as complexation between Pb2+ and N atom
      in the chitin, and further adsorption of Pb2+ nearby the complexed Pb2+ and
      precipitation of the hydrolysis product of the Pb2+ complex on the beads as the
      crystalline state. Furthermore, structural factors such as larger surface area of
      the beads resulted from microporous-network structure, low crystallinity of
      cellulose/chitin beads and high hydrophilicity induced by hydrophilic skeleton of
      cellulose played an important role in increasing adsorption ability.

PMID- 16112170
TI  - Effect of citric acid on aluminum hydrolytic speciation.
AB  - The mechanisms of the influence of organics on Al transformation were not fully
      understood. This study investigated the effect of citric acid on Al speciation in
      partially neutralized aluminum solution. The partially neutralized solution was
      prepared with 20 mmol L(-1) AlCl3 without citrate (citrate/Al molar ratio of 0,
      control) or with citrate (citrate to Al molar ratios between 0.1 and 3.0) at pH
      between 3.0 and 7.0. The nature of aluminum hydrolytic products as influenced by
      citrate complexation was investigated by turbidity measurement, ferron kinetic
      color development, peak line width in 27Al nuclear magnetic resonance (NMR)
      deconvolution demodule quantitative methods, and the MinteqA2 chemical speciation
      program. Sulfate precipitates from Al solution as influenced by citrate were
      examined by X-ray diffraction (XRD) analysis and atomic force microscopy (AFM).
      The turbidity of the Al solution increased with increasing pH values. Increases
      in citrate/Al molar ratio from 0 to 0.1 decreased dramatically the turbidity due
      to citrate complexation. The 27Al NMR peak at 6 ppm of the Al solution at a
      citrate/Al molar ratio of 0.5 shifted to 8 and 10 ppm in the solutions at
      citrate/Al molar ratio of 1.0 and 3.0, respectively. Comparison of 27Al NMR data
      and the data obtained from the MinteqA2 chemical speciation program, indicate
      that the Al-citrate complexes as revealed by 27Al NMR data are largely
      Al(citrate), AlH(citrate)+, and Al(citrate)(2)3- complexes (99-112%) in the pH
      range of 4.5-6.5. The non-detected Al fractions by the MinteqA2 program account
      for 82-99% of the non-detected Al fractions by NMR quantitation in the same pH
      range. The AFM of sulfate precipitates from solutions with low citrate/Al molar
      ratios (i.e., 0.01, pH 4.5, aged 40 days) shows that Al13 sulfate precipitates
      were ellipse-shaped. These ellipse-shaped precipitates were aggregated when
      solution pH increased from 4.5 to 7.0 (aged 40 days), indicating the fast
      hydrolytic rate of Al at high pH. The sulfate precipitates from solution with a
      high citrate/Al molar ratio (i.e., 0.05, pH 4.5, aged 40 days) also shows
      aggregate of particles, and XRD non-crystallized precipitates the hampering
      effect of citrate on Al precipitates.

PMID- 16112171
TI  - Effects of widely used pharmaceuticals and a detergent on oxidative stress
      biomarkers of the crustacean Artemia parthenogenetica.
AB  - Pharmaceuticals are continuously dispersed into the environment as a result of
      human and veterinary use, posing relevant environmental concerns. The present
      paper reports the acute toxic effects of three therapeutic agents (diazepam,
      clofibrate and clofibric acid) and a detergent, sodium dodecylsulphate (SDS), to
      the hypersaline crustacean Artemia parthenogenetica. This study specially focused
      on oxidative stress parameters, namely (1) total and selenium-dependent
      glutathione-peroxidase (GPx), (2) glutathione reductase (GRed), (3) total
      superoxide dismutase (SOD), and (4) glutathione-S-transferases (GSTs). The
      effects of tested substances on lipid peroxidation (thiobarbituric acid reactive
      substances, TBARS), and soluble cholinesterases (ChE) were also investigated.
      Diazepam caused a significant inhibition of ChE (LOEC = 7.04 mg/l) and total GPx
      activities. SDS was responsible for a decrease in the activity of both ChE (LOEC
      = 8.46 mg/l) and GRed (LOEC = 4.08 mg/l). Both fibrates (clofibrate and clofibric
      acid) were responsible for significant decreases in Se-dependent GPx, with LOEC
      values of 176.34 and 3.09 mg/l, respectively. Clofibrate also caused a slight
      increase of TBARS content of A. parthenogenetica homogenates. These results
      indicate that the exposure to all the tested compounds induced alterations on the
      cellular redox status in A. parthenogenetica. In addition, diazepam was shown to
      have the capability of interfering with A. parthenogenetica neurotransmission,
      through the inhibition of ChE.

PMID- 16112172
TI  - Phytotoxicity of nitroaromatic energetic compounds freshly amended or weathered
      and aged in sandy loam soil.
AB  - The toxicities of 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitrobenzene (TNB), 2,4
      dinitrotoluene (2,4-DNT), and 2,6-dinitrotoluene (2,6-DNT) to terrestrial plants
      alfalfa (Medicago sativa L.), Japanese millet (Echinochloa crusgalli L.), and
      perennial ryegrass (Lolium perenne L.) were determined in Sassafras sandy loam
      soil using seedling emergence, fresh shoot, and dry mass measurement endpoints. A
      13-week weathering and aging of energetic materials in soils, which included
      wetting and drying cycles, and exposure to sunlight of individual soil
      treatments, was incorporated into the study design to better reflect the soil
      exposure conditions in the field than toxicity determinations in freshly amended
      soils. Definitive toxicity tests showed that dinitrotoluenes were more phytotoxic
      for all plant species in freshly amended treatments based on EC20 values for dry
      shoot ranging from 3 to 24mgkg(-1) compared with values for TNB or TNT ranging
      from 43 to 62mgkg(-1). Weathering and aging of energetic materials (EMs) in soil
      significantly decreased the toxicity of TNT, TNB or 2,6-DNT to Japanese millet or
      ryegrass based on seedling emergence, but significantly increased the toxicity of
      all four EMs to all three plant species based on shoot growth. Exposure of the
      three plant species to relatively low concentrations of the four compounds
      initially stimulated plant growth before the onset of inhibition at greater
      concentrations (hormesis).

PMID- 16112173
TI  - Study on fractions of adsorbed Pb and Cd onto natural surface coatings.
AB  - The speciation and extent of migration of adsorbed Pb and Cd in natural surface
      coatings (NSCs) were investigated using sequential extraction procedure to
      provide an understanding of distribution of the adsorbed Pb and Cd. Extractions
      were conducted on NSCs before and after Pb and Cd adsorption treatment under
      controlled laboratory conditions with initial Pb and Cd concentrations ranging
      from 0.2-2.5 mol/l. The Langmuir adsorption isotherms were applied to estimate
      equilibrium coefficients of Pb and Cd adsorption to NSCs components. The results
      showed that 58.50% of adsorbed Pb in average existed in tightly adsorbed form,
      and the remaining Pb was mostly present as solid oxides/hydroxides (34.00%) and
      exchangeable and soluble form (7.50%) in NSCs, respectively. Large amount of
      adsorbed Cd (70.51% in average) was present in exchangeable and soluble form,
      following a decreasing order in tightly adsorbed form (18.61%), solid
      oxides/hydroxides (9.87%), and easily oxidizable solids/compounds (1.01%),
      respectively. No Cd was found in strongly held oxides and precipitates. Compared
      to the distribution of adsorbed Pb in NSCs, Cd distribution showed that less
      migration of Cd from exchangeable and soluble form to solid oxides/hydroxides
      after adsorbed to NSCs, indicating fewer sites for Cd to adsorb to NSCs and less
      affinity of Cd to the NSCs. These percent distributions of metals provided an
      additional interpretation to that Pb adsorption to the NSCs greater than that of
      Cd, less retention of Cd than that of Pb and less roles attributed for Pb/Cd
      adsorption by organic materials in NSCs, which were observed based on the
      selective extraction techniques in the independent investigations.

PMID- 16112174
TI  - Patient-provider communication and perceived control for women experiencing
      multiple symptoms associated with ovarian cancer.
AB  - OBJECTIVES: Optimal cancer symptom management requires effective patient-health
      care provider (HCP) communication. The goals of this study were to 1) describe
      symptom experiences of women with ovarian cancer, 2) evaluate frequency of
      patient-HCP communication about symptoms, and 3) evaluate whether communication
      is associated with patients' confidence in managing symptoms. METHODS: This was a
      cross-sectional mailed survey study. The Symptom Experience Survey, containing
      valid, reliable measures of symptom severity and controllability; symptom
      communication; and symptom-related coping strategies, was mailed to members of
      the National Ovarian Cancer Coalition. Descriptive statistics, t tests,
      correlations, and ANCOVA were used to address study objectives. RESULTS: This
      analysis focuses on the 279 respondents who had active disease. The majority of
      women had recurrent disease (96%) and were on chemotherapy (57%). Women reported
      a mean of 12 concurrent symptoms. Fatigue, bowel disturbances, and peripheral
      neuropathies were the most severe and most noticed symptoms. Only 61% of women
      had discussed their most noticed symptom with an HCP in the past month, and only
      50% of women reported that they had received symptom management recommendations.
      Women reported low levels of perceived control over symptoms (M = 1.97 on a 0-4
      scale). There was a significant interaction effect for symptom discussions and
      management recommendations on perceived control. Women who had never received
      recommendations had low perceived control whether or not they had discussed their
      symptom with an HCP in the past month. For women who had received
      recommendations, those who had discussed their symptom with an HCP in the past
      month had higher perceived control compared to those who had not discussed their
      symptom. CONCLUSIONS: Women with ovarian cancer experience multiple symptoms, but
      many do not discuss symptoms with their HCPs and fewer report receiving symptom
      management recommendations. Women would benefit from more active symptom
      assessment and discussion of management strategies by HCPs.

PMID- 16112175
TI  - Ovarian malignant melanoma: unusual presentation of a solitary metastasis.
AB  - BACKGROUND: Malignant melanomas of the ovary are rare with unpredictable clinical
      and biological behavior. We present this case report of a metastatic ovarian
      malignant melanoma, where the ovary was the first site of relapse after 10 years
      of remission. CASE: A 58-year-old postmenopausal woman was incidentally found to
      have an abdominal mass, 10 years after removal of a cutaneous malignant melanoma
      lesion. Ultrasound and CT scan revealed an adnexal mass, which was found to be a
      solitary ovarian tumor at laparotomy. Histology confirmed malignant melanoma
      metastasis. CONCLUSION: Relapse after a prolonged period of remission,
      presenting, as an isolated ovarian metastasis is an unusual presentation of
      malignant melanoma. As illustrated by this case report, a differential diagnosis
      of a metastatic malignant melanoma must be considered.

PMID- 16112176
TI  - Invasive potency related to RCAS1 expression in uterine cervical cancer.
AB  - OBJECTIVES: RCAS1 expression is significantly associated with clinical prognosis
      in various human cancers, which suggests that RCAS1 may be involved in
      acquisition of malignant phenotypes. To investigate the relationship between
      RCAS1 and one such characteristic, tumor invasiveness, we examined RCAS1
      expression in cervical neoplasms ranging from the precancerous state to invasive
      cancer. METHODS: RCAS1 expression was studied retrospectively via
      immunohistochemical methods. Samples consisted of biopsy tissue from 90 patients
      with intraepithelial neoplasia and resected tumor tissue from 154 patients with
      invasive cancer. Statistical analysis was done to correlate RCAS1 expression and
      clinicopathologic variables in patients with a depth of cancer cell invasion into
      stromal tissue of >5 mm. RESULTS: RCAS1 expression was detected in patients with
      intraepithelial cancer and invasive cancer but not in patients with dysplasia.
      The occurrence and degree of RCAS1 expression increased with the depth of
      invasion. In patients with invasive cancer, RCAS1 overexpression was
      significantly correlated with invasion of the lymph-vascular space, lymph node
      metastasis in two or more sites, and tumor volume; RCAS1 expression was not
      associated with histologic subtype. Overall survival rates for patients with
      RCAS1 overexpression were significantly shorter than those for patients without
      RCAS1 overexpression. In connective tissue surrounding tumor cells, the number of
      cells expressing vimentin significantly decreased in relation to RCAS1 expression
      level. Moreover, significant associations between expression levels of RCAS1 and
      those of MMP-1 and laminin-5 were found. CONCLUSION: RCAS1 may contribute to
      acquisition of malignant uterine cervical phenotypic characteristics including
      invasion, metastasis, and tumor growth via connective tissue remodeling.

PMID- 16112177
TI  - A phase I/II trial of weekly topotecan and carboplatin in potentially platinum
      sensitive relapsed ovarian and peritoneal carcinoma.
AB  - OBJECTIVE: Topotecan and carboplatin are active in relapsed ovarian cancer, but
      attempts to combine these agents are limited by myelotoxicity. This phase I/II
      trial combined weekly topotecan, which is less myelosuppressive than the standard
      5-day regimen, with carboplatin in patients with potentially platinum-sensitive
      relapsed ovarian or peritoneal carcinoma (PS-OVCa/PCa). METHODS: Eligible
      patients had PS-OVCa/PCa, performance status 0-2, and normal bone marrow, renal,
      and hepatic functions. On day 1 of a 21-day cycle, patients received carboplatin
      (area under the curve [AUC] 5) followed by topotecan 2.0 mg/m2, both via 30-min
      intravenous infusion. Topotecan 2.0 mg/m2 also was administered on days 8 and 15.
      Treatment was withheld for neutropenia or thrombocytopenia on day 8 or 15. Dose
      escalation was planned. RESULTS: Seventeen patients received a total of 115
      (median, 6) cycles of chemotherapy. With carboplatin AUC 4, neutropenia prevented
      dose escalation of topotecan; hematologic toxicity caused 34/105 (32%) weekly
      treatments to be withheld. However, carboplatin could be dose escalated to AUC 5
      when the day 15 dose of topotecan was withheld. In the intent-to-treat
      population, there were 4 (24%) complete and 9 (53%) partial responses, 2 (12%)
      patients (at the carboplatin AUC 4 dose) with stable disease, and 2 (12%)
      nonevaluable patients. CONCLUSION: Carboplatin (AUC 5) on day 1 in combination
      with topotecan 2.0 mg/m2 on days 1 and 8 of a 21-day cycle is well tolerated and
      active in patients with PS-OVCa/PCa. A phase II trial comparing this with other
      carboplatin therapeutic doublets in patients with recurrent ovarian cancer is
      warranted.

PMID- 16112179
TI  - Antitumor effect of cotylenin A plus interferon-alpha: possible therapeutic
      agents against ovary carcinoma.
AB  - OBJECTIVE: Recently, we found that cotylenin A and IFNalpha synergistically
      inhibited growth both in vitro and in vivo, and induced apoptosis in human cancer
      cells. For the clinical application of this combined treatment, suitable cancer
      targets should be selected. METHODS: We examined the combined effects of these
      compounds on various types of cancer cells by a human cancer cell line panel
      assay, and on cancer cells that had been freshly isolated from patients in three
      dimensional cultures embedded in collagen gel. RESULTS: In the analysis of 39
      cancer cell lines, ovarian cancer cells were highly sensitive to combined
      treatment with cotylenin A and IFNalpha in inhibiting cell growth. This treatment
      was also effective toward ovarian cancer cells that were refractory to CDDP, and
      significantly inhibited the growth of ovarian cancer cells as xenografts without
      apparent adverse effects. Ovarian cancer cells from the patients were also
      sensitive to the combined treatment in primary cultures. CONCLUSION: Combined
      treatment with cotylenin A and IFNalpha may have therapeutic value in treating
      ovarian cancer.

PMID- 16112178
TI  - Altered mRNA expressions of sialyltransferases in ovarian cancers.
AB  - OBJECTIVE: Aberrant glycosylation occurs in essentially all types of experimental
      and human cancers, and many glycosyl epitopes constitute tumor-associated
      antigens (for example, CA125). Many recent studies have indicated that some, if
      not all, aberrant glycosylation is a result of altered sialyltransferase (ST)
      expression; however, there is little known of the role of the altered mRNA
      expression of ST in ovarian cancers. METHODS: Alterations in ST mRNA expression
      in postmenopausal ovarian tissues, including those of normal controls (n=24) and
      malignant serous ovarian cancers (n=24), were examined by means of real-time
      quantitative reverse transcription-polymerase chain reaction (RTQ-PCR). Maackia
      Amurensis Agglutinin type 2 (MAA) specific foralpha2,3-linked NeuNAc was used for
      immunohistochemical staining. RESULTS: Among these five STs, the mRNA expressions
      of three STs, including ST3Gal III, ST3Gal IV, and ST3Gal VI, were significantly
      decreased in patients with ovarian cancers, compared to the normal controls
      (P<0.001). By contrast, the mRNA expressions of ST3Gal I and ST6Gal I were
      increased in ovarian cancer tissues, compared to those of the normal controls
      (P<0.001). The ovarian epithelial carcinoma part showed strong positivity for
      MAA, whereas MAA staining in the stromal part was negative. Both the epithelial
      part and the stromal part of postmenopausal ovarian tissue showed negativity for
      MAA staining. However, clinico-pathological parameters, including stage,
      differentiation, amount of ascites, and serum levels of CA125, did not show any
      correlation to mRNA expression of any given-type ST. CONCLUSIONS: Our results
      suggest that altered mRNA expressions of alpha2,3-sialyltransferase ST3Gal I,
      ST3Gal III, ST3Gal IV, ST3Gal VI, andalpha2,6-sialyltransferase ST6Gal I are of
      importance in malignant ovarian cancers. An increased expression of ST3Gal I may
      contribute directly to increased alpha2,3-linked sialylation in ovarian serous
      carcinoma.

PMID- 16112180
TI  - Human papillomavirus load in Hybrid Capture II assay: does increasing the cutoff
      improve the test?
AB  - OBJECTIVE: The aim of the study was to evaluate whether the results of the Hybrid
      Capture II (HCII) assay for detecting high-grade squamous intraepithelial lesions
      (H-SIL) or cervical carcinoma can be improved by increasing the relative light
      units (RLU) level. STUDY DESIGN: We included 2271 women (mean age 38.7 +/- 12.3,
      range 15-92) referred to a colposcopic clinic due to cytology of atypical cells
      of unknown significance, SIL or carcinoma. All women underwent a new Pap test, HR
      HPV detection using HCII and colposcopy with biopsy of suspicious areas when
      present. RESULTS: HR-HPV was detected in 91.7% of carcinomas, 96.6% of H-SIL,
      85.1% of low-grade SIL and 21.6% of cases with no lesion. The probability of
      harboring an H-SIL or a carcinoma significantly increased as RLU increased (P =
      0.01). The sensitivity and specificity for H-SIL or carcinoma at different
      cutoffs were 95.7 and 54.6 at 1 RLU, 93.9 and 59.6 at 2 RLU, 90.1 and 65.1 at 5
      RLU and 85.7 and 68.7 at 10 RLU. The percentage of cases not detected with HCII
      increased from 2.4% for cases with <1 RLU to 9.5% for cases between 1 and 2 RLU,
      14.8% between 2 and 3 RLU, 21.7% between 3 and 5 RLU and 28.4% between 5 and 10
      RLU. CONCLUSION: The use of a higher cutoff (higher viral load) in the HCII
      should not be recommended because it significantly increases the number of cases
      with H-SIL or carcinoma not detected, reducing the sensitivity and negative
      predictive value of the test.

PMID- 16112181
TI  - GnRH antagonist in the adjuvant treatment of a recurrent ovarian granulosa cell
      tumor: a case report.
AB  - BACKGROUND: Ovarian granulosa cell tumors (GCT) are usually treated by surgery
      and chemotherapy. Successful response to GnRH agonists as an adjuvant therapy has
      previously been reported. In this case of recurrent GCT, we used a GnRH
      antagonist. CASE: A 78-year-old woman underwent surgery for an ovarian granulosa
      cell tumor (pT1a N0 Mx). Six months later, laparotomy revealed an inoperable
      recurrence of the tumor. Experimental treatment with a GnRH antagonist was not
      clearly successful. This is in contrast to the previously proven benefit of GnRH
      agonist therapy in this type of malignancy and to the positive response elicited
      by GnRH antagonists in epithelial ovarian tumors. CONCLUSION: GnRH antagonist
      therapy had no demonstrable efficacy in the treatment of a poorly differentiated
      and aggressive recurrent granulosa cell tumor.

PMID- 16112182
TI  - Feasibility of laparoscopic peritonectomy followed by intra-peritoneal
      chemohyperthermia: an experimental study.
AB  - OBJECTIVE: Hyperthermic intraperitoneal chemotherapy (HIPEC) is being evaluated
      for patients with minimal residual or no residual disease after primary surgery
      and chemotherapy for stage III ovarian carcinoma. The use of operative
      laparoscopy to perform peritonectomy and HIPEC is reported. METHODS: Five adult
      pigs were used. The placement of trocars in the four quadrants was planned in
      order to complete a total peritonectomy and then to place the HIPEC drains. The
      umbilical trocar was then replaced manually by the surgeon through a Lapdisc to
      manipulate the bowel loops. The abdominal cavity was filled with heated saline
      (43 degrees C), and the pumps were activated for 30 min. RESULTS: The procedure
      was successfully completed with an adequate intraabdominal temperature and
      distribution. CONCLUSION: These preliminary data suggest the technical
      feasibility of the laparoscopic approach for HIPEC, in an animal model without
      carcinomatosis. Our ongoing research is designed to gather pharmacokinetic data
      in an experimental controlled randomized fashion to compare a laparoscopic to a
      laparotomy approach on the same model.

PMID- 16112183
TI  - The successful double cryopreservation of rabbit (Oryctolagus cuniculus) semen in
      large volume using the directional freezing technique with reduced concentration
      of cryoprotectant.
AB  - Using directional freezing, our objective was to cryopreserve rabbit semen and
      achieve fertility that was equal or higher than that achieved with conventional
      freezing. The working hypothesis was that controlling the ice-front propagation
      would allow reduction of DMSO concentration to <1M, in addition to the capability
      to freeze large volumes (2-10 mL). Moreover, single and double freezing of semen
      were used to demonstrate the abbreviated mechanical stress imparted by
      directional freezing. Single-cryopreserved semen from 15 males extended with 0%
      egg yolk/1.75 M DMSO, 15.3% egg yolk/0.88 M DMSO and 20% egg yolk/0M DMSO
      resulted in lower (P<0.05) mean+/-S.E.M. post-thaw motility (3.6+/-1.1, 28.5+/
      2.8 and 36.3+/-1.8%, respectively) compared to fresh semen (73.3+/-1.2%). Semen
      from seven of these males, subject to double freezing using only egg yolk based
      extenders, resulted in post-thaw motilities of 18.1+/-2.2 and 16.4+/-3.3%.
      Despite the reduced functional parameters of cryopreserved semen, fertility and
      kindling rates of 73.9 and 56.5% for single frozen-thawed, and 28.6 and 35.7% for
      double frozen-thawed semen were achieved (with insemination of 98 females). There
      was no significant difference in fertility rate between fresh semen (87.5%) and
      semen that was single frozen-thawed with the 15.3% egg yolk/0.88 M DMSO extender
      (73.9%). In conclusion, cryopreservation of rabbit semen in large volumes using
      directional freezing achieved fertility rates similar to those achieved with
      fresh semen. Furthermore, acceptable fertility rates with double frozen-thawed
      semen could facilitate the future use of sex-sorted semen in rabbits.

PMID- 16112184
TI  - Assessment of pronuclear formation following in vitro fertilization with bovine
      spermatozoa obtained after thermal insulation of the testis.
AB  - This study was conducted to follow the chronology of pronuclear formation in
      bovine zygotes after in vitro insemination with a population of spermatozoa
      having abnormal morphology. Semen samples were obtained and cryopreserved from
      four Holstein bulls before and after a scrotal insulation period of 48 h (Day 0).
      A pre-insult (Day 5) and a Day 20 post-insult semen sample were evaluated for
      morphology and used for IVF after standard swim-up sperm separation protocols.
      Pronuclear formation was scored on subpopulations of presumptive zygotes after
      they were fixed and stained at 3-h time intervals from 6 to 18 h post in vitro
      insemination (hpi). Post-thaw morphological evaluation of semen samples revealed
      a decrease in the percentages of normal spermatozoa in the post-insult samples
      compared with the pre-insult samples for Bull I (74-22%) and Bull III (68-1%).
      The sperm penetration rate decreased (P<0.05) between the pre- and post-insult
      samples for Bulls I (90-76%) and III (92-70%), but was not different for Bulls II
      (92-90%) and IV (78-85%). The pronuclear formation rates for post-insult zygotes
      for Bulls II and IV had comparable increases in development over time, whereas
      there was no increase in the pronuclear development for the zygotes from the post
      insult samples for Bulls I and III, and generally a condensed sperm head was
      observed in the oolemma. At 18 hpi the fertilization rate between the pre- and
      post-insult samples for Bulls I (51-4%), II (88-75%) and III (94-2%) decreased
      (P<0.01), but there was no change for Bull IV (66%). In conclusion, we inferred
      that the failure in normal pronuclear formation was associated with an absence of
      normal decondensation of the penetrating spermatozoon; this suggested that the
      effect of morphologically abnormal spermatozoa occurred prior to cleavage, thus
      limiting early development.

PMID- 16112185
TI  - Copper, oxidative stress, and human health.
AB  - Copper (Cu), a redox active metal, is an essential nutrient for all species
      studied to date. During the past decade, there has been increasing interest in
      the concept that marginal deficits of this element can contribute to the
      development and progression of a number of disease states including
      cardiovascular disease and diabetes. Deficits of this nutrient during pregnancy
      can result in gross structural malformations in the conceptus, and persistent
      neurological and immunological abnormalities in the offspring. Excessive amounts
      of Cu in the body can also pose a risk. Acute Cu toxicity can result in a number
      of pathologies, and in severe cases, death. Chronic Cu toxicity can result in
      liver disease and severe neurological defects. The concept that elevated
      ceruloplasmin is a risk factor for certain diseases is discussed. In this paper,
      we will review recent literature on the potential causes of Cu deficiency and Cu
      toxicity, and the pathological consequences associated with the above. Finally,
      we will review some of the potential biochemical lesions that might underlie
      these pathologies. Given that oxidative stress is a characteristic of Cu
      deficiency, the role of Cu in the oxidative defense system will receive special
      attention. The concept that excess Cu may be a precipitating factor in
      Alzheimer's disease is discussed.

PMID- 16112186
TI  - Iron and copper metabolism.
AB  - Iron and copper are essential nutrients, excesses or deficiencies of which cause
      impaired cellular functions and eventually cell death. The metabolic fates of
      copper and iron are intimately related. Systemic copper deficiency generates
      cellular iron deficiency, which in humans results in diminished work capacity,
      reduced intellectual capacity, diminished growth, alterations in bone
      mineralization, and diminished immune response. Copper is required for the
      function of over 30 proteins, including superoxide dismutase, ceruloplasmin,
      lysyl oxidase, cytochrome c oxidase, tyrosinase and dopamine-beta-hydroxylase.
      Iron is similarly required in numerous essential proteins, such as the heme
      containing proteins, electron transport chain and microsomal electron transport
      proteins, and iron-sulfur proteins and enzymes such as ribonucleotide reductase,
      prolyl hydroxylase phenylalanine hydroxylase, tyrosine hydroxylase and aconitase.
      The essentiality of iron and copper resides in their capacity to participate in
      one-electron exchange reactions. However, the same property that makes them
      essential also generates free radicals that can be seriously deleterious to
      cells. Thus, these seemingly paradoxical properties of iron and copper demand a
      concerted regulation of cellular copper and iron levels. Here we review the most
      salient characteristics of their homeostasis.

PMID- 16112187
TI  - Role of matrix metalloproteinases in inflammatory bowel disease.
AB  - Recent evidence demonstrates that the increased expression and activity of matrix
      metalloproteinases (MMPs) may contribute to intestinal tissue injury and
      inflammation in inflammatory bowel disease, and that MMP inhibition might be a
      new therapeutic approach to controlling inflammatory response. In addition, MMPs
      may play a crucial role in physiological and pathophysiological reactions such as
      leukocyte accumulation into inflamed tissue, cytokine production from
      inflammatory and epithelial cells, T lymphocyte homing to the intestine, wound
      healing and proliferation of epithelial cells, and intestinal innate immunity.
      This review focuses on recent progress in elucidating the biological and
      pathological roles of MMPs in inflammatory bowel disease.

PMID- 16112188
TI  - Is there a role for copper in neurodegenerative diseases?
AB  - Copper is an essential metal in living organisms; thus, the maintenance of
      adequate copper levels is of vital importance and is highly regulated.
      Dysfunction of copper metabolism leading to its excess or deficiency results in
      severe ailments. Two examples of illnesses related to alterations in copper
      metabolism are Menkes and Wilson diseases. Several proteins are involved in the
      maintenance of copper homeostasis, including copper transporters and metal
      chaperones. In the last several years, the beta-amyloid-precursor protein (beta
      APP) and the prion protein (PrP(C)), which are related to the neurodegenerative
      disorders Alzheimer and prion diseases respectively, have been associated with
      copper metabolism. Both proteins bind copper through copper-binding domains that
      also have been shown to reduce copper in vitro. Moreover, this ability to reduce
      copper is associated with a neuroprotective effect exerted by the copper-binding
      domain of both proteins against copper in vivo. In addition to a functional link
      between copper and beta-APP or PrP(C), evidence suggests that copper has a role
      in Alzheimer and prion diseases. Here, we review the evidence that supports both,
      the role of beta-APP and PrP(C), in copper metabolism and the putative role of
      copper in neurodegenerative diseases.

PMID- 16112189
TI  - Brief report: associations of parental warmth, peer support, and gender with
      adolescent emotional distress.
AB  - This is an exploratory study of the associations among parental warmth, peer
      support, gender, and emotional distress in a sample of 308 adolescents in the
      United States. Parental warmth was associated with less emotional distress,
      whereas turning to peers for support during family conflict was associated with
      more emotional distress. Gender moderated these associations in multivariate
      analyses. Emotional distress was highest among females who reported low levels of
      parental warmth and who turned to peers for support, in comparison with females
      who also turned to peers for support but had higher parental warmth. Findings
      contribute to a growing literature on contextual factors associated with
      adolescent psychosocial well-being.

PMID- 16112190
TI  - Temperature effects on alpha-crystallin structure probed by 6-bromomethyl-2-(2
      furanyl)-3-hydroxychromone, an environmentally sensitive two-wavelength
      fluorescent dye covalently attached to the single Cys residue.
AB  - The single Cys residue in the C-terminal domain of bovine eye lens alpha
      crystallin was covalently labelled with 6-bromomethyl-2-(2-furanyl)-3
      hydroxychromone. This novel SH-reactive two-band ratiometric fluorescent dye is
      characterized by excited state intramolecular proton transfer reaction yielding
      two highly emissive N* and T* bands separated by more than 100 nm. Their relative
      intensities are known to be highly sensitive to the H-bonding ability of the
      environment. Properties of the environment of the dye attached to the protein
      were studied under native-like conditions and at a range of elevated temperatures
      that are known to facilitate alpha-crystallin chaperone-like activity. We observe
      that on heating, the environment of the dye becomes more flexible and the H
      bonding of the dye with the protein vicinity decreases. The spectroscopic
      properties observed on heating were partially restored after cooling, but the
      initial values were not reached on the time scale of our experiments (up to 3 h).
      This suggests that the changes of the dye microenvironment are connected with the
      rearrangements of alpha-crystallin quaternary structure. Since there is only one
      Cys residue in alphaA subunit of alpha-crystallin (whereas alphaB subunit
      contains no Cys), we attributed the observed temperature-induced changes of the
      dye's microenvironment to the particular site within alpha-crystallin molecule.

PMID- 16112191
TI  - Fluoride modification effects on osteoblast behavior and bone formation at TiO2
      grit-blasted c.p. titanium endosseous implants.
AB  - Increasing bone formation at endosseous titanium implants may be achieved by
      modification of topographically enhanced surfaces. The aim of this study was to
      determine the effect of fluoride ion modification of TiO2 grit-blasted, c.p.
      titanium implants on osteoblastic differentiation and interfacial bone formation
      by parallel in vitro and in vivo investigations. Human mesenchymal stem cells
      (Osiris Therapeutics, Inc.) were cultured on TiO2 grit-blasted c.p.titanium disks
      with and without fluoride ion modification. Cell adhesion, proliferation, and
      osteoblastic gene expression was measured by scanning electron microscopy,
      tritiated-thymidine uptake into insoluble DNA, and reverse transcription
      polymerase chain reaction detection of mRNAs encoding collagen 1, osteopontin,
      bone sialoprotein, osteocalcin and BMP-2. After 24 h, there were no differences
      in cell adhesion among the surfaces tested. Fluoride-treated surfaces supported
      greater proliferation and increased bone sialoprotein and BMP-2 expression.
      Additionally, 12 TiO2 grit-blasted and 12 fluoride ion modified implants were
      placed randomly into medial and distal osteotomies prepared in the tibia of 300 g
      Sprague Dawley rats. After 21 days, the tibiae were harvested and 100 microm
      ground sections were examined by backscatter scanning electron microscopy. The
      bone-to-implant contact formed at TiO2 grit-blasted and fluoride-treated versus
      TiO2 grit-blasted surfaces was 55.45% versus 34.21% (p<0.027), respectively.
      Fluoride ion modification of the TiO2 grit-blasted surface enhanced osteoblastic
      differentiation in vitro and interfacial bone formation in vivo. This parallel in
      vitro and in vivo investigation demonstrates that fluoride ion modification
      enhanced osteoblastic differentiation and interfacial bone formation. The
      mechanism(s) by which fluoride ion modification of c.p.titanium enhanced
      osteoblastic differentiation and osseointegration merit careful investigation.

PMID- 16112192
TI  - Human stem cell factor-antibody [anti-SCF] enhances chemotherapy cytotoxicity in
      human CD34+ resistant myeloid leukaemia cells.
AB  - Acute myeloid leukaemia (AML) is a heterogenous malignant disease with diverse
      biological features in which disease progression at the level of CD34+ cells has
      a major impact on the resistance to chemotherapy and relapse. The AML blast cells
      in these elderly patients are often characterised by several unfavourable
      covariates that predict the poor treatment outcome, including high stem cell
      marker CD34 expression, minimally or undifferentiated features, high P
      glycoprotein expression, high bcl-2/bax ratio, unfavourable karyotype and more
      frequent internal tandem duplications (ITDs) and mutations of class III receptor
      type tyrosine kinase for key haematopoietic cytokines: Flt-3 (receptor for Flt
      ligand), c-kit (receptor for stem cell factor) and fms (receptor for M-CSF).
      Testing the new and more specific molecular-targeted therapeutic approaches in
      CD34+ AML cells can provide the basis for a more effective combined
      molecular/chemotherapy regimen and may consequently improve the treatment outcome
      in elderly AML patients. Therefore, the present study was performed to evaluate
      whether stem cell factor-antibody (anti-SCF) can enhance the efficacy of the two
      main chemotherapeutic drugs used in AML therapy: cytarabine and daunorubicin at
      low doses in human-resistant CD34+ AML cells, in an attempt to identify a novel
      effective regimen with tolerable side-effects for elderly AML patients. The
      effect of anti-SCF on each of the two chemotherapeutic drugs-induced apoptosis
      and necrosis was investigated in KG1a human-resistant CD34+ AML cells expressing
      P-glycoprotein to determine its enhancing activity. Anti-SCF has significantly
      enhanced the low dose cytarabine- and daunorubicin-induced apoptosis+necrosis in
      KG1a CD34+ AML cells from 12.0+/-1.7 to 40.9+/-5.9% and from 16.3+/-0.9 to 48.9+/
      1.0%, respectively, p<0.01. It has also exerted its significant enhancement
      activity on the low dose cytarabine- and daunorubicin-induced apoptosis+necrosis
      in KG1a CD34+ AML cells in the presence of SCF, p<0.05. Anti-SCF has
      significantly enhanced the low dose cytarabine- and daunorubicin-induced bcl-2
      reduction in KG1a CD34+ AML cells from 26.7+/-0.6 to 64.6+/-1.0% and from 59.8+/
      3.1 to 80.1+/-7.9%, respectively, p<0.01. The addition of SCF has not altered the
      low dose cytarabine- and daunorubicin-induced bcl-2 reduction in KG1a CD34+ AML
      cells (Table 4). Anti-SCF has also significantly enhanced the low dose cytarabine
      and daunorubicin-induced bcl-2 reduction in KG1a CD34+ AML cells in the presence
      of SCF, p<0.05. The unique potent enhancing activity of anti-SCF on low dose
      chemotherapy-induced apoptosis and necrosis in extremely resistant AML cells
      suggest a novel promising role for the treatment of elderly AML patients. Further
      studies are warranted to evaluate a similar enhancing effect for anti-SCF in
      blast cells from elderly AML patients in primary cultures before its introduction
      in a pilot clinical study. In conclusion, the combination of anti-SCF and the low
      dose cytarabine provides a promising solution for the dilemma of therapy in
      elderly AML patients.

PMID- 16112193
TI  - Analysis of PTEN deletions and mutations in multiple myeloma.
AB  - Clonal plasma cells from patients with multiple myeloma (MM), plasma cell
      leukemia (PCL) and human myeloma cell lines (HMCLs) were analyzed for
      deletions/mutations of the tumor suppressor gene PTEN. By interphase-FISH,
      hemizygous PTEN deletions were detected in 4 (5.6%) of 71 MM patients, 2 (20%) of
      10 PCLs, and 2 (20%) of 10 HMCLs. PTEN deletions were detected in 4 MM patients
      at diagnosis with stage III disease (Durie-Salmon). Of the six cases with PTEN
      deletions, 1 MM had a 13q deletion, 1 PCL had a t(11;14), and the other PCL had a
      t(14;16), a 13q deletion and a p53 deletion. Sequencing analysis did not detect
      PTEN mutations in 11 primary MM and 5 PCL cases. Our results indicate that
      alterations of PTEN are uncommon in MM patients, and PTEN deletions tend to occur
      in advanced disease suggesting that they are secondary, rather than primary,
      events in the pathogenesis of MM.

PMID- 16112194
TI  - Effects of insect growth regulators on the nontarget soil arthropod Folsomia
      candida (Collembola).
AB  - The aim of this study was to assess the effect of several insect growth
      regulators (IGRs) on the nontarget soil arthropod Folsomia candida (Collembola).
      The survival and reproduction rates of F. candida were evaluated after 28 days of
      exposure to six IGRs (methoprene, fenoxycarb, precocene II, tebufenozide,
      hexaflumuron and teflubenzuron) and to one herbicide (diuron) in artificial soil.
      The differences in the sensitivity of F. candida to these different substances
      are high. The chitin synthesis inhibitors teflubenzuron and hexaflumuron were the
      most toxic compounds with an EC50 of 0.05 mg/kg (dry weight) for teflubenzuron
      and an EC50 of 0.6mg/kg for hexaflumuron. Teflubenzuron is toxic for F. candida
      at concentrations that are probably close to environmental levels of this
      insecticide. Inhibition of reproduction is strongly related to adult survival for
      the juvenile hormone agonist methoprene and for the antijuvenile hormone
      precocene II, with an EC50 of 173 mg/kg and a LC50 of 178mg/kg for methoprene and
      an EC50 of 15 mg/kg and a LC50 of 26 mg/kg for precocene II. Fenoxycarb, another
      juvenile hormone analog, showed a dose-response curve for mortality different
      from that of methoprene; at concentrations such as 3052 mg/kg no effect on adult
      survival was observed. However, the EC50 value of 113mg/kg is of the same order
      of magnitude as that obtained for methoprene. A test with compressed soil
      contaminated with fenoxycarb was conducted to observe parameters such as numbers
      of eggs laid and juveniles hatched. No differences were observed between these
      two endpoints for fenoxycarb. An EC50 of 109 mg/kg was obtained for the ecdysone
      agonist tebufenozide. The herbicide diuron showed a relatively high toxicity for
      F. candida with an EC50 of 20 mg/kg. Our results show that some of the tested
      IGRs can have effects on Collembola at environmentally relevant concentrations
      (toxicity/exposure ratios < 5 for teflubenzuron, hexaflumuron, and diuron).

PMID- 16112195
TI  - Buffalo (Bubalus bubalis) interleukin-12: analysis of expression profiles and
      functional cross-reactivity with bovine system.
AB  - Interleukin-12, a heterodimeric pro-inflammatory cytokine, from water buffaloes
      (Bubalus bubalis) was analyzed for its for its tissue specific expression and
      functionality. Concanavalin A stimulated splenocytes displayed an up-regulation
      of the IL-12 p40 subunit 8-24h post-stimulation, whereas the p35 subunit did not
      show any quantitative variation at different time intervals. Basal level
      expressions of both the subunits were observed by RT-PCR in spleen. In addition
      p40 transcripts could be detected in liver and p35 in brain and muscle tissues as
      well in very low levels. Functional recombinant buffalo IL-12 was expressed in
      HEK 293T cells as a heterodimer using foot-and-mouth disease virus 2A polypeptide
      as a linker. Culture supernatants from transfected cells contained a hetero
      dimeric p70 subunit as revealed in western blot of the proteins separated by
      native polyacrylamide gel electrophoresis (PAGE) using a monoclonal antibody
      against bovine IL-12 p40. IL-12 containing culture supernatant induced production
      of nitric oxide in cultured splenocytes of both buffalo and bovine origin. Our
      study reveals that buffalo IL-12, which shares a high-level sequence identity
      with bovine IL-12, also has functional cross-reactivity with the bovine immune
      cells.

PMID- 16112196
TI  - Extra-hepatic transcription of the human mannose-binding lectin gene (mbl2) and
      the MBL-associated serine protease 1-3 genes.
AB  - Mannose-binding lectin (MBL) is a part of the innate immune defense and activates
      complement via MBL associated serine proteases (MASPs). Human MBL is expressed by
      hepatocytes, but recent evidence in mice indicates a substantial extra-hepatic
      transcription. Therefore, we investigated whether mRNA transcribed from the human
      mbl2 gene as well as the masp genes was present in different tissues. The
      transcription of human mbl2 is regulated by two alternative promoters (named 0
      and 1) where promoter 0 derived transcripts include an additional 5' untranslated
      part encoded by an extra exon (exon 0). Low extra-hepatic levels of mbl2 mRNA
      were predominantly found in small intestine and testis tissue, and were
      quantitatively dominated by promoter 1 transcripts. Moreover, these transcripts
      varied due to the use of alternative acceptor splice sites positioned inside exon
      1. The mRNA distribution of masp1 and masp2 were found very similar to that of
      mbl2, while masp3 mRNA seemed ubiquitous present at quite high levels when
      compared to liver. These results indicate that the regulation of mbl2 gene
      expression in man is more complex than previously anticipated and that local
      expression of MBL may be relevant in local immune defense, particularly in
      restricted areas of the gastrointestinal and reproductive tracts.

PMID- 16112197
TI  - Structures and homology modeling of chicken major histocompatibility complex
      protein class I (BF2 and beta2m).
AB  - In order to elucidate the two-dimensional (2D) and three-dimensional (3D)
      structures of chicken major histocompatibility complex (MHC) class I protein (BF2
      and beta2m) and further reconstruct their complex identifying the virus-derived
      antigenic peptides, the mature protein of BF2 and beta2m genes were expressed
      solubility in pMAL-p2X/Escherichia coli. TB1 system. The expressed MBP-BF2- and
      MBP-beta2m-fusion proteins were purified, and cleaved by the factor Xa protease.
      Subsequently, the monomers were further separated, and the purified MBP-BF2, 
      beta2m, and MBP were analyzed by circular dichroism (CD) spectrum. The contents
      of alpha-helix, beta-sheet, turn, and random coil in BF2 protein were 72, 102,
      70, and 90 amino acids (aa), respectively. The beta2m proteins displayed a
      typical beta-sheet and the contents of alpha-helix, beta-sheet, turn, and random
      coil were 0, 46, 30, and 22 aa, respectively. Homology modeling of BF2 and beta2m
      proteins were similar as the 3D structure of human MHC class I (HLA-A2). The
      results showed that pMAL-p2X expression and purification system could be used to
      obtain the right conformational BF2 and beta2m proteins, and the 2D and 3D
      structures of BF2 and beta2m were revealed to be similar to human's. The
      recombinant BF2 and beta2m-based proteins might be a powerful tool for further
      detecting antigenic peptides.

PMID- 16112198
TI  - Rapid qualitative protease microassay (RPM).
AB  - A rapid qualitative protease microassay (RPM) was developed as an alternative to
      conventional assays of cysteine protease activity in HPLC fractions. Using this
      technique protease activity in samples could be visually determined within 5 min.
      The method was sensitive to 3.3x10(-7) U/mL of papain and detected cysteine
      protease activity in dilute HPLC fractions with activity of 5.4x10(-5) U/mL.
      Because the method monitors the decolorization of Coomassie Brilliant Blue
      stained substrate, it can be modified to detect other classes of proteases.

PMID- 16112199
TI  - Chemometrics-assisted simple UV-spectroscopic determination of carbamazepine in
      human serum and comparison with reference methods.
AB  - In the present report, carbamazepine is determined on serum samples of real
      patients by a procedure completely assisted by chemometric tools. First, a
      response surface methodology based on a mixture design was applied in order to
      select the best conditions for the extraction step. Finally, partial least
      squares multivariate calibration (PLS-1) was applied to second-derivative UV
      spectra, eliminating a shift baseline effect that originated in the extraction
      procedure. The performance assessment included: (a) a three-level precision
      study, (b) a recovery study analyzing spiked samples, and (c) a method comparison
      with high-performance liquid chromatography (HPLC) and fluorescence polarization
      immunoassay (FPIA) applied on real patient samples. The obtained results show the
      potentiality of the presently studied methodology for the monitoring of patients
      treated with this anticonvulsant.

PMID- 16112200
TI  - Maintaining the ionic permeability of a cellulose ester membrane.
AB  - This paper reports the results of a series of experiments designed to test
      conditions that would permit NaCl to diffuse through 100 Da molecular weight cut
      off (MWCO) and 1,000 Da MWCO membranes. For the 100 Da MWCO membrane, the
      membrane becomes completely impermeable to NaCl when dialyzed against distilled
      water (DW), but inclusion of one of a variety of different salts in the dialyzing
      solution maintains membrane permeability to NaCl. A titration experiment revealed
      that a minimum concentration of 0.1 mM of a salt such as KH2PO4 is required to
      sustain membrane permeability. In contrast, diffusion through the 1,000 Da MWCO
      membrane was slightly higher when DW was used as the dialysate. We conclude that
      the 100 Da MWCO membrane works well for a variety of dialysis applications
      provided that a maintenance salt is included in all dialyzing solutions.

PMID- 16112201
TI  - Analysis of mGluR1a constitutive internalization using a pulse-chase enzyme
      linked immuno-sorbant assay (ELISA).
AB  - The surface expression of G protein-coupled receptors is regulated by
      internalization. For many receptors, a constitutive level of internalization in
      the absence of agonist has been reported. The constitutive internalization of
      metabotropic glutamate receptor 1a (mGluR1a) has been described, but in general
      little attention has been dedicated to this important aspect of receptor
      regulation. Here we describe a pulse-chase ELISA method that allows the
      investigation of mGluR1a constitutive internalization. When investigated by pulse
      chase ELISA, the constitutive internalization of mGluR1a was inhibited by
      dominant negative mutant constructs of arrestin-2 or Eps-15. This observation,
      besides indicating the arrestin- and clathrin-dependence of mGluR1a constitutive
      internalization, also confirmed the physiological relevance of the method
      described in this article. Confocal microscopy experiments to study receptor
      localization further validated the pulse-chase labelling procedure. The
      application of the pulse-chase ELISA to mGluR1b, revealed that this splice
      variant undergoes marginal constitutive internalization. Two COOH-terminal
      deletion mutants of mGluR1a, DMI (Arg847stop) and DMII (Arg868stop), were also
      tested for constitutive internalization. Interestingly, only DMII underwent
      significant constitutive internalization, suggesting that the region between
      Arg847 and Arg868 might play a regulatory role in mGluR1a trafficking. Taken
      together, the pulse-chase ELISA appears to be an efficient tool to analyze the
      constitutive internalization of different mGluR1 splice variants.

PMID- 16112202
TI  - Psychiatric disorders and their comorbidity in subjects with parasuicide by
      intentional drug overdose: prevalence and gender differences.
AB  - The aims of the present study were to assess the prevalence and comorbidity of
      psychiatric disorders in subjects with intentional drug overdose and to explore
      whether there were gender differences in prevalence and comorbidity. A
      standardized psychiatric evaluation was performed in 100 randomly selected
      subjects, 18 years old and older, with intentional drug overdose referred to an
      emergency department. The prevalences of psychiatric morbidity and comorbidity
      were very high in both genders: 88% presented with at least one psychiatric
      diagnosis, and three-quarters presented with comorbid psychiatric disorders.
      Affective and anxiety disorders were the most prevalent diagnoses. One patient
      out of three presented with alcohol or substance misuse. Compared to females,
      males suffered five times more often from substance misuse and three times more
      often from psychotic syndrome and were three times less likely to present with
      anxiety disorder. When subjects are referred to hospital for intentional drug
      overdose, medical management should systematically involve a psychiatric
      assessment in order to identify not only affective and anxiety disorders, but
      also alcohol and substance misuse, due to the high prevalence of these disorders,
      especially in male subjects.

PMID- 16112203
TI  - Neurochemical effects of cocaine in adolescence compared to adulthood.
AB  - Adolescence is a time of high risk behavior and increased exploration. This
      developmental period is marked by a greater probability to initiate drug use and
      is associated with an increased risk to develop addiction and adulthood
      dependency. Human adolescents are predisposed toward an increased likelihood of
      risk taking behaviors [M. Zuckerman, Sensation-seeking and the endogenous deficit
      theory of drug abuse. NIDA Res Monogr. 74 (1986) 59-70.], including drug use or
      initiation. In the present study, adolescent and adult animals were first tested
      on several behavioral measures (novel environment exploratory behavior, novel
      object preference, novelty-induced impulsivity and novelty-induced exploration)
      which were used to categorize them as high- (HR) or low-responders (LR). The
      purpose of the present study was to characterize the neurochemical responsivity
      of the nucleus accumbens septi (NAcc) in HR and LR adolescent and adult animals
      in response to a systemic challenge of cocaine. Regardless of age, animals that
      were more reactive when placed in a novel environment had greater cocaine-induced
      increases in dopamine (DA). Several important and complex neurochemical
      differences existed between adolescent and adult animals. Adolescent animals that
      rapidly approached the novel object (i.e., HR) were the only group to show
      greater cocaine-induced responsivity. However, adult animals that spent less time
      near the novel object (i.e., LR) were the only group to have greater cocaine
      induced responsivity. Adolescent animals that approached a novel object faster
      (HR) showed an increased dopaminergic (DAergic) response to an acute cocaine
      challenge. In contrast, adolescent animals that spent less time with the novel
      object had an increased cocaine-induced DAergic response compared to HR adults.
      Adults that approached the object less had a greater cocaine-induced DA response
      relative to HR adults. Finally, cocaine yielded a greater DA response in
      adolescent animals that showed a high novelty-induced exploration and impulsivity
      response, whereas the opposite was true for adults. The differences in response
      to cocaine between ages and groups are likely due to ontogenetic differences in
      brain regions that are involved in reward and/or stress responsivity.

PMID- 16112204
TI  - A single course of antenatal betamethasone reduces neurotrophic factor S100B
      concentration in the hippocampus and serum in the neonatal rat.
AB  - The effects of a single course of antenatal betamethasone on S100B protein
      concentration were investigated in Fisher 344 rats. On day 20 of gestation,
      pregnant rats were injected twice 8 h apart with either (1) 170 microg kg(-1)
      body weight betamethasone ("clinically-equivalent dose", equivalent to 12 mg
      twice, 24 h apart in humans), (2) half of this dose (equivalent to 6 mg) or (3)
      vehicle. We report reference values for S100B protein in the serum and different
      brain regions in both genders at 1, 2, and 21 days after birth. Interestingly,
      S100B concentration showed a time-dependent and brain region-specific pattern of
      expression. At P1, S100B was higher in the serum of males compared to females. In
      addition, we show that both doses of betamethasone decreased S100B concentration
      in the serum of males at P1, whereas in the hippocampus, it was reduced by the
      clinically-equivalent dose only. This suggests that lowering the dose of
      antenatal betamethasone may be less detrimental for brain maturation and
      therefore we reiterate the need for clinical trials with a low dose regimen.

PMID- 16112205
TI  - Intraoperative evaluation of a pulsatile oropharyngeal mass during
      adenotonsillectomy.
AB  - Iatrogenic injury to the internal carotid artery (ICA) is a rare complication of
      pharyngeal surgery that most commonly occurs in children with an anomalous course
      to the internal carotid artery. Most aberrant arteries are asymptomatic. They can
      remain undiscovered preoperatively or be found incidentally on radiographic
      studies completed for an unrelated reason. Evaluation of definitive internal
      carotid artery injuries is well documented in the trauma literature. We present a
      case of a suspected intraoperative injury to the internal carotid artery during
      routine pharyngeal surgery. Ultimately no injury was found, however, aberrant
      internal carotid arteries were coincidentally discovered.

PMID- 16112206
TI  - Prognosis of airway obstruction and feeding difficulty in the Robin sequence.
AB  - OBJECTIVE: To evaluate the course and prognosis of airway obstruction and feeding
      difficulty in the Pierre Robin sequence (PRS). METHODS: Retrospective review of
      60 patients with PRS between 1993 and 2002 at the University of California, Davis
      Medical Center. Patients were placed into diagnostic subgroups: (1) Isolated PRS;
      (2) Syndromic PRS (known syndrome with PRS); (3) Unique PRS (unique anomalies
      with PRS). Data regarding severity, duration, and management of airway
      obstruction and feeding difficulty were collected. RESULTS: Airway obstruction
      requiring intervention beyond positional therapy was seen in 28% isolated, 42%
      syndromic, and 58% unique PRS. One-third of patients who failed positional
      therapy were temporarily stabilized with a nasopharyngeal airway or endotracheal
      intubation. The remaining two-thirds of patients, who failed positional therapy
      required a surgical airway procedure. Four patients underwent mandibular
      distraction osteogenesis, resulting in successful decannulation or avoidance of
      tracheostomy. Thirteen patients underwent tracheostomy; mean duration of
      tracheostomy-dependence was 17.0 months in Isolated PRS and 31.7 months in Unique
      PRS (p < 0.01). Successful decannulation by age of 3 years was confirmed in 85%
      of patients who underwent tracheostomy. Tube feeding was required in 53%
      Isolated, 67% Syndromic, and 83% Unique PRS. Forty-two percent of PRS patients
      with a successful positional airway still demonstrated feeding difficulty. Short
      term (0-3 months) and intermediate (4-18 months) tube feeding was more commonly
      required in Isolated and Syndromic PRS, while long-term (beyond 18 months)
      gastrostomy tube feeding was more commonly required in Unique PRS (p < 0.01). By
      3 years of age, a successful oral diet was seen in 91% Isolated, 92% Syndromic,
      and 78% Unique PRS. CONCLUSIONS: Diagnostic subgroups based on the presence of
      additional anomalies help families and physicians in understanding the severity
      and duration of feeding and airway difficulty in PRS. Two-thirds of PRS patients
      who fail positional therapy may ultimately require a surgical airway procedure.
      Feeding difficulty can be present in the absence of clinically significant airway
      obstruction. Families and physicians should be encouraged that by 3 years of age,
      most patients were successfully taking an oral diet without airway obstruction.

PMID- 16112207
TI  - The use of viral vectors to produce hepatitis B virus core particles in plants.
AB  - The expression and assembly of the hepatitis B virus (HBV) nucleocapsid protein
      (HBcAg) were investigated in plants using viral vectors. Constructs based on
      either Potato virus X (PVX) or Cowpea mosaic virus (CPMV) containing the sequence
      of HBcAg were able to infect the appropriate host plants and remained genetically
      stable during infection. Analysis of HBcAg expression revealed that the protein
      can self-assemble into core-like particles and that the assembled material could
      be partially purified by differential centrifugation. Thus, the use of viral
      vectors can be considered a practical method for rapid production of assembled
      HBcAg particles in plants. This approach provides a means whereby a variety of
      chimaeric particles can be assessed quickly and cheaply for various diagnostic
      and vaccine applications.

PMID- 16112208
TI  - Antiviral efficacy of VP14637 against respiratory syncytial virus in vitro and in
      cotton rats following delivery by small droplet aerosol.
AB  - VP14637, the lead compound in a series of substituted bis-tetrazole
      benzhydrylphenols developed by ViroPharma Incorporated, was evaluated for
      antiviral efficacy against respiratory syncytial virus (RSV) in vitro in cell
      culture and in vivo in cotton rats. A selective index of >3000 (> or =2000 times
      greater than that observed for ribavirin) was determined in the in vitro studies
      for this compound against both RSV A and B subtypes. In cotton rats, animals
      given as little as 126 microg drug/kg by small droplet aerosol in divided doses
      starting 1 day after experimental virus infection with either a RSV A or B
      subtype consistently had significantly lower mean pulmonary RSV titers and
      reduced histopathological findings than mock-treated animals or cotton rats given
      placebo (vehicle-treated animals). No cotton rat treated with aerosols of VP14637
      during these studies manifested any evident untoward responses. Thus, VP14637
      exhibited good selective antiviral efficacy both in vitro and in vivo.

PMID- 16112209
TI  - Cell-based and biochemical screening approaches for the discovery of novel HIV-1
      inhibitors.
AB  - The identification of novel HIV-1 inhibitors is facilitated by screening
      campaigns that combine the right screening strategy with a large diverse
      collection of drug-like compounds. Cell-based screening approaches offer some
      advantages in the quest for novel inhibitors because they can include multiple
      targets in a single screen and in some cases reveal targets and/or structures not
      captured in biochemical assays. However, follow-up activities for cell-based
      screens are often more complicated and resource intensive when compared to
      biochemical screens. Alternatively, biochemical screens usually offer the
      advantage of focusing on a single target with a well-defined set of follow-up
      assays. In this review we cover multiple cell-based and biochemical assay
      formats, many of which were designed to identify inhibitors that act through new
      mechanisms. Some of the assays discussed have been utilized in antiviral screens
      while others might be formatted for HTS or utilized as secondary assays in a
      screening campaign. As drug discovery efforts in the pharmaceutical industry
      shift away from traditional strategies, new approaches such as those presented
      here are likely to play a significant role in the identification of next
      generation HIV-1 inhibitors.

PMID- 16112210
TI  - Cholin- and carboxylesterase activities in developing zebrafish embryos (Danio
      rerio) and their potential use for insecticide hazard assessment.
AB  - Insecticides are a potential hazard for non-target organisms like fish
      particularly at run off events. The study of effects to embryos of the zebra fish
      Danio rerio is already an accepted tool in waste water monitoring, but effects of
      various groups of substances (like most pesticides) to the zebrafish embryo
      remain to be studied. Enzymes are often taken as biomarkers of exposure and
      effect. Therefore cholinesterase isozymes and carboxylesterase were examined for
      their suitability as biomarkers of insecticide exposure. The activities of
      cholinesterase and of carboxylesterase were monitored in the first 48 h post
      fertilization (hpf) of zebrafish development. Significant specific activities in
      the range of 0.5-25 U could be measured from the sixth somite stage (12 h) up to
      the Long Pec stage (48 h) for different cholinesterases using acetyl-, acetyl
      beta-methyl-, butyryl- and propionylthiocholin as substrates. The specific
      activity of carboxylesterase ranged from 4 to 16 Umg(-1) protein in the
      respective developmental stages. Substrate specificity was analysed using
      specific inhibitors (eserine sulphate, DPDA, BW284c51). The results showed that
      the observed cholinesterase activities in the whole embryo may be attributed
      mainly to acetylcholinesterase with a partial capability to use
      propionylthiocholine as a second substrate. The potential use of cholin- and
      carboxylesterase as biomarkers was investigated using the organophosphate
      paraoxon-methyl. A 40% inhibition of enzyme activities was reached by 0.4 microM
      paraoxon-methyl indicating the possible use of these enzymes as biomarkers of
      exposure.

PMID- 16112211
TI  - Taurine suppresses platelet-derived growth factor (PDGF) BB-induced PDGF-beta
      receptor phosphorylation by protein tyrosine phosphatase-mediated
      dephosphorylation in vascular smooth muscle cells.
AB  - In atherosclerosis, abnormal vascular smooth muscle cell (VSMC) proliferation
      plays an important role to form fibroproliferative lesions and platelet-derived
      growth factor (PDGF)-BB is one of the most potent chemoattractants and
      proliferative factors for VSMCs. Taurine, sulfur-containing beta-amino acid, has
      been considered to prevent the development of atherosclerosis, although the
      molecular mechanism remains obscure. Previously, we demonstrated that taurine
      significantly suppressed PDGF-BB-induced cell proliferation, DNA synthesis,
      immediate-early gene expressions and extracellular signal-regulated kinase (ERK)
      1/2 phosphorylation in VSMCs. The present study was aimed at elucidating the
      precise molecular mechanism of taurine in PDGF-BB signaling pathway. We showed
      that taurine significantly suppressed PDGF-BB-induced phosphorylation of PDGF
      beta receptor and activation of its downstream signaling molecules such as Ras,
      MAPK/ERK kinase (MEK)1/2 and Akt. Because taurine did not attenuate phorbol 12
      myristate 13-acetate (PMA)-induced PDGF-beta receptor-independent ERK1/2
      phosphorylation, we further investigated the suppressive mechanism of taurine in
      PDGF-beta receptor level. Although taurine did not directly affect PDGF receptor
      autophosphorylation in vitro, taurine promoted PDGF-beta receptor
      dephosphorylation and restored PDGF-BB-induced suppression of protein tyrosine
      phosphatase (PTPase) activity. Taken together, we propose that taurine could
      prevent or delay the progression of atherosclerosis by PTPase-mediated
      suppression of PDGF-beta receptor phosphorylation, and by decreasing the
      activation of its downstream signaling molecules in VSMCs.

PMID- 16112212
TI  - Suppression of macrophage responses to bacterial lipopolysaccharide (LPS) by
      secretory leukocyte protease inhibitor (SLPI) is independent of its anti-protease
      function.
AB  - Secretory leukocyte protease inhibitor (SLPI), a potent serine protease
      inhibitor, has been shown to suppress macrophage responses to bacterial
      lipopolysaccharide (LPS). SLPI contains two topologically superimposable domains.
      Its C-terminal domain binds and inhibits target proteases. It is not clear
      whether SLPI's anti-protease function plays a role in the LPS-inhibitory action
      of SLPI. Four single amino acid substitution mutants of SLPI, M73G, M73F, M73E
      and M73K, were generated. Wild type SLPI is a potent inhibitor of chymotrypsin
      and elastase. Mutants M73G and M73F selectively lost inhibitory function towards
      chymotrypsin and elastase, respectively, whereas mutants M73K and M73E inhibited
      neither elastase nor chymotrypsin. Macrophage cell lines were established from
      RAW264.7 cells to stably express each SLPI mutant. Expression of the SLPI
      protease inhibition mutants suppressed NO and TNF production in response to LPS
      in a similar fashion as wild type SLPI. Expression of truncated forms of SLPI,
      containing only its N-terminus or its C-terminus, was similarly sufficient to
      confer inhibition of LPS responses. Thus, the LPS-inhibitory action of SLPI is
      independent of its anti-protease function.

PMID- 16112213
TI  - Analysis of differential protein expression in Acidithiobacillus ferrooxidans
      grown under different energy resources respectively using SELDI-ProteinChip
      technologies.
AB  - Surface-enhanced laser desorption/ionization (SELDI)-time of flight is an
      affinity-based mass spectrometric method in which proteins of interest are
      selectively absorbed to a chemically modified surface on a chip, which allows
      proteomic analysis with limited material requirements. This characteristic makes
      it a valuable technique for microbiologists handling problematic samples, such as
      low cell number cultures. In this study, we explored differential-expressed
      proteome of Acidithiobacillus ferrooxidans cultivated with Fe(2+) and elemental
      sulfur separately by adopting the protein biochip SELDI approach. The cell
      lysates of A. ferrooxidans were applied onto Ciphergen ProteinChip WCX2, SAX2 and
      IMAC-Cu arrays. Proteins bound to the chips were analyzed on a ProteinChip Reader
      Model PBS II. A summary of the molecular masses of the differentially regulated
      proteins found on WCX2, IMAC-Cu and SAX2 was obtained and 28 differentially
      expressed proteins were found on the molecular weight range of 5.0 to 25 kDa.

PMID- 16112215
TI  - The contribution of AERPs (MMN and LDN) to studying temporal vs. linguistic
      processing deficits in children with reading difficulties.
AB  - One of the factors responsible for the appearance of reading problems seems to be
      a difficulty in discriminating auditory stimuli presented in rapid succession,
      known as the 'temporal processing hypothesis'. In this study automatic
      discrimination processes were evaluated in 31 children with reading difficulties
      and 24 control children between 4 and 8 years of age, using a passive oddball
      paradigm, in which syllables (/ba/ and /da/) and complex tones were presented.
      Analysis of the MMN component revealed significant differences between the groups
      only in the task involving linguistic stimuli, detecting longer latency of the
      component in the experimental group. The LDN component showed lower amplitudes
      and delayed latencies in the experimental group during the processing of both
      types of stimuli. These differences, however, were more marked in the task
      involving syllables, where a higher mean amplitude was observed in the
      experimental group than in the control group in the right hemisphere. The task
      involving complex tones also revealed differences between the groups at the
      frontal electrodes, indicating different maturative courses of the potential. The
      findings demonstrate the existence of a strongly pronounced preattentional
      auditory deficit during phonological processing, and also reveal important
      differences between the various stages of automatic information processing in
      children with and without reading disabilities.

PMID- 16112214
TI  - Erythropoietin receptor is not a surrogate marker for tumor hypoxia and does not
      correlate with survival in head and neck squamous cell carcinomas.
AB  - BACKGROUND AND PURPOSE: To evaluate erythropoietin receptor (EPOR) expression in
      human head and neck squamous cell carcinomas and correlate this to the presence
      of tumor hypoxia and treatment outcome. PATIENTS AND METHODS: Eighty-five
      patients with locally advanced tumors of the head and neck were included. Of
      these, 34 were given the hypoxia marker pimonidazole i.v. 2 h prior to biopsy
      taking. Contiguous paraffin embedded biopsies were stained for EPOR expression
      and, if administered, for pimonidazole binding. Immunohistochemical staining for
      EPOR was interpreted semiquantitatively according to a composite scale, ranging
      from 0 to 200. Pimonidazole positivity was quantitatively analyzed in a
      semiautomatic way. RESULTS: Diffuse weak-to-moderate cytoplasmic and membrane
      EPOR immunostaining was observed in 80 of 85 biopsies (94%) and staining scores
      ranged from 0 to 198 (median 100). No correlations were found between EPOR
      expression, and the primary tumor site, T-stage or N-stage. Also, There was no
      association between EPOR expression and treatment outcome. The degree of tumor
      hypoxia represented by the relative area of pimonidazole binding varied between 0
      and 26% (median 7%). Contiguous biopsy sections showed a lack of colocalization
      between EPOR and pimonidazole binding. CONCLUSION: EPOR expression was
      demonstrated in the majority of the head and neck tumors. No colocalization was
      found between EPOR expression and pimonidazole binding indicating that the
      presence or absence of hypoxia did not necessarily indicate a distinct pattern of
      EPOR expression. The level of EPOR expression was not of prognostic significance
      in patients with head and neck cancer, although small effects of EPOR cannot be
      excluded because of the sample size of this study.

PMID- 16112216
TI  - Fate redirection of hippocampal astrocytes toward neuronal lineage by aggregate
      culture.
AB  - Mammalian cells that have been committed to a certain cell lineage cannot be
      directed to other lineages. However, some astrocytes in the mammalian brains have
      been reported to represent plasticity to redirect to other cell lineages. We
      found that mouse hippocampal astrocytes cultured in aggregate forms of
      "astrosphere", redirected to MAP2-positive immature neurons. In astrospheres,
      basic HLH factors positively regulating neuronal differentiation were up
      regulated and Id3 inhibiting basic HLH factors was down-regulated. Ectopic Id3
      induction repressed redirection of astrocytes to a neuronal lineage, suggesting
      that astrosphere formation induced plasticity of astrocytes by changing the gene
      expression patterns.

PMID- 16112217
TI  - Identification and characterization of PorH, a new cell wall channel of
      Corynebacterium glutamicum.
AB  - The cell wall of Corynebacterium glutamicum contains the cation-selective channel
      (porin) PorA(C.glut) and the anion-selective channel PorB(C.glut) for the passage
      of hydrophilic solutes. Lipid bilayer experiments with organic solvent extracts
      of whole C. glutamicum cells cultivated in minimal medium suggested that also
      another cation-selective channel-forming protein, named PorH(C.glut), is present
      in C. glutamicum. The protein was purified to homogeneity by fast-protein liquid
      chromatography across a HiTrap-Q column. The pure protein had an apparent
      molecular mass of about 12 kDa on SDS-PAGE. Western blot analysis suggested that
      the cell wall channel is presumably formed by protein oligomers. The purified
      protein forms cation-selective channels with an average single-channel
      conductance of about 2.5 nS in 1 M KCl in the lipid bilayer assay. The
      PorH(C.glut) protein was partially sequenced, and based on the resulting amino
      acid sequence, the corresponding gene, designated as porH(C.glut), was identified
      in the published genome sequence of C. glutamicum ATCC13032. PorH(C.glut)
      contains only the inducer methionine but no N-terminal extension, which suggests
      that the export and assembly of the protein follow a yet unknown pathway.
      PorH(C.glut) is coded in the bacterial chromosome by a gene that is localized in
      the vicinity of porA(C.glut), within a putative operon of 13 genes. RT-PCR
      revealed that both porins are cotranscribed. They coexist according to
      immunological detection experiments in the cell wall of C. glutamicum together
      with PorB(C.glut) and PorC(C.glut).

PMID- 16112218
TI  - Cell-free xenogenic vascular grafts fixed with glutaraldehyde or genipin: in
      vitro and in vivo studies.
AB  - Chronic rejection of arterial xenografts results in aneurysmal dilation, due to
      immune mediated processes. To minimize the immunologic degradation of the graft,
      a cell-extraction process employing sodium dodecyl sulfate (SDS) was used in the
      study to remove the cellular components in bovine carotid arteries. To further
      reduce their immunogenicity, the acellular arteries were fixed with
      glutaraldehyde (A-GA) or genipin (A-GP). The in vitro properties of all test
      samples were analyzed. Additionally, the in vivo performance of the heparinized A
      GA and A-GP grafts (H-A-GA and H-A-GP) was evaluated in a canine model. It was
      found that the SDS treatment effectively removed cells from the arterial wall,
      but the main structures of the extracellular matrix were preserved with a portion
      of the water-soluble glycosaminoglycans removed. After cell extraction, the
      elastic lamellae in the media became straightened, and thus made the tissue less
      extensile. The heparinized tissues significantly reduced platelet adhesion. At
      retrieval, all implanted grafts were patent and not dilated. Chronic inflammatory
      response surrounding the implants was observed. However, fixation of acellular
      tissues by glutaraldehyde or genipin inhibited immune cell penetration into the
      media and limited tissue degradation, and therefore prevented the arterial wall
      from dilation. Nevertheless, the H-A-GP graft was superior to the H-A-GA graft in
      completeness of endothelialization on its luminal surface, and thus precluded
      thrombus formation.

PMID- 16112220
TI  - Genetical identification of Akebia and Aristolochia species by using
      Pyrosequencing.
AB  - This study was performed to determine if Akebia and Aristolochia species (Akebia
      quinata Decaisne and Aristolochia manshuriensis Kom.) could be identified by
      genetic analysis of Pyrosequencing method, which is used to assess genetic
      variation. The Pyrosequencing results of Akebia and Aristolochia species showed
      different patterns. The Pyrosequencing analysis of A. quinata Decaisne was very
      different compared with that of A. manshuriensis Kom. Pyrosequencing analyses
      might be able to identify the Akebia and Aristolochia species.

PMID- 16112219
TI  - Colorimetric detection of eukaryotic gene expression with DNA-derivatized gold
      nanoparticles.
AB  - Thiol-linked DNA-gold nanoparticles were used in a novel colorimetric method to
      detect the presence of specific mRNA from a total RNA extract of yeast cells. The
      method allowed detection of expression of the FSY1 gene that encodes a specific
      fructose/H+ symporter in Saccharomyces bayanus PYCC 4565. FSY1 is strongly
      expressed when the yeast is grown in fructose as the sole carbon source, while
      cells cultivated in glucose as the sole carbon source repress gene expression.
      The presence of FSY1 mRNA is detected based on color change of a sample
      containing total RNA extracted from the organism and gold nanoparticles
      derivatized with a 15-mer of complementary single stranded DNA upon addition of
      NaCl. If FSY1 mRNA is present, the solution remains pink, changing to blue-purple
      in the absence of FSY1 mRNA. Direct detection of specific expression was possible
      from only 0.3 microg of unamplified total RNA without any further enhancement.
      This novel method is inexpensive, very easy to perform as no amplification or
      signal enhancement steps are necessary and takes less than 15 min to develop
      after total RNA extraction. No temperature control is necessary and color change
      can be easily detected visually.

PMID- 16112221
TI  - Phosphorus fractions and phosphate sorption characteristics in relation to the
      sediment compositions of shallow lakes in the middle and lower reaches of Yangtze
      River region, China.
AB  - Phosphorus is recognized as the most critical nutrient limiting lake
      productivity. The trophic status and development of lake systems are also
      influenced by the phosphorus content and fractions and phosphate sorption
      characteristics of the lake sediments. The phosphorus fractions and phosphate
      sorption characteristics of sediments in shallow lakes from the middle and lower
      reaches of Yangtze River region in China were investigated. The results show that
      the phosphorus contents in the sediments ranged from 217.8 to 1640 mg kg(-1);
      inorganic phosphorus (IP) was the major fraction of total phosphorus (TP);
      phosphorus bound to Al, Fe, Mn oxides, and hydroxides (Fe/Al-P), and calcium
      bound phosphorus (Ca-P) were the main fractions of IP. Phosphate sorption on the
      sediments mainly occurred within 2 h and then reached equilibrium in 10 h. The
      phosphate sorption rate was closely related to the concentration of fine
      particles. The phosphate sorption capacity ranged from 128.21 to 833.33 mg kg(
      1), showing a significant correlation with the contents of Fe, Fe+Al, total
      organic carbon (TOC), cationic exchange capacity, total nitrogen, TP, Ca, IP, and
      the ratio of P/(Al+Fe), and it was higher in the sediments of eutrophic lakes
      than in mesotrophic lakes. Phosphate was mainly sorbed onto Fe and Al particles.
      The phosphate sorption efficiency ranged from 26.74 to 312.50 L kg(-1), and had a
      strong positive correlation with Fe content. For the eutrophic lake sediments,
      there were no significant relationships between the phosphate sorption efficiency
      and the selected physical and chemical parameters. But for the mesotrophic lake
      sediments, the phosphate sorption efficiency was found to be positively related
      to the contents of Al and Fe+Al.

PMID- 16112222
TI  - Hydrogen and methane sorption in dry and water-loaded multiwall carbon nanotubes.
AB  - Both H2 and CH4 are clean energy sources. Adsorption was considered a measure to
      enhance their storage, and many efforts have been dedicated to creating novel
      materials including carbon nanotubes as efficient carriers for them. In order to
      understand the uptake mechanism and the viability of practical application, eight
      adsorption isotherms of H2 on a sample of multiwall carbon nanotubes were
      collected. The heat of adsorption was determined and an isotherm model was
      presented. Isotherms of CH4 on the same sample were also collected. While the
      adsorption on dry samples behaves similarly to that of H2, the sorption behavior
      of CH4 in the water-loaded sample is quite different and five times higher uptake
      capacity was observed in the wet sample due to the formation of methane hydrates.
      However, carbon nanotubes are unlikely to be used as an energy carrier due to its
      limited surface area and pore volume.

PMID- 16112223
TI  - Fast exopolysaccharide secretion of Pseudomonas aeruginosa on polar polymer
      surfaces.
AB  - The influence of the surface chemical structure and related physicochemical
      properties on the adhesion of P. aeruginosa has been studied for moderately
      hydrophobic polymers and for hydrophilic surfaces obtained by O2-plasma
      treatments and 50 keV Ar+ beam irradiation of poly(hydroxymethylsiloxane) and
      poly(ethyleneterephthalate). The surface chemical structure has been obtained by
      X-ray photoelectron spectroscopy, the roughness was measured by atomic force
      microscopy, and the surface free energy was evaluated from contact angle
      measurements for all the polymer substrates before and after the irradiation
      treatments. It is shown that a massive and unusually fast secretion of
      exopolysaccharides onto highly polar surfaces, corresponding to the formation of
      complex three-dimensional multilayers (i.e., biofilm-like structures), occurs
      already after 2 h of incubation. It is suggested that such highly polar surfaces
      can operate either by promoting, by means of a still unknown biomolecular
      mechanism, an early gene expression process or by mimicking the P. aeruginosa
      cellular walls.

PMID- 16112224
TI  - Solvent-induced shape evolution of PVP protected spherical silver nanoparticles
      into triangular nanoplates and nanorods.
AB  - The reaction between silver nitrate and poly(N-vinyl-2-pyrrolidone) (PVP) in
      pyridine at ambient conditions could lead to the formation of spherical
      nanoparticles or quadrilateral and triangular silver nanoplates, depending on the
      silver-to-PVP ratio used. It is proposed that the spherical Ag nanoparticles,
      which were formed early in the reaction, were transformed into nanoplates through
      an Ostwald ripening process driven by the bridging flocculation of small
      spherical Ag nanoparticles. This unique and hitherto unreported shape evolution
      process was carefully followed by a combination of techniques, viz., UV-visible
      spectroscopy, TEM, and powder X-ray diffraction.

PMID- 16112225
TI  - The effect of block copolymer EPE1100 on the colloidal stability of Mg-Al LDH
      dispersions.
AB  - The adsorption isotherm of block copolymer EPE1100 (polyethylene oxide
      polypropylene oxide-polyethylene oxide) on the surfaces of Mg-Al LDH particles
      was determined through a solution depletion method combined with TOC measurement.
      X-ray diffraction patterns showed that the adsorption of EPE1100 molecules only
      occurred on the outer surfaces of LDH particles and they did not intercalate into
      the galleries between the layers. The adsorption of EPE1100 molecules changed the
      morphology of the particles. The effect of EPE1100 on the colloidal stability of
      LDH dispersion was investigated from three aspects: after the freezing-melting
      cycle, after the shearing rotations, and after the addition of electrolyte. The
      results indicated that the effect of EPE1100 on the colloidal stability of LDH
      dispersions was strongly related to the state of copolymer adsorption on LDH
      particle surfaces. It was inferred that the hydrated repulsive force and steric
      repulsive force played important roles in determining the stability of the
      dispersions.

PMID- 16112226
TI  - Preparation and colloidal stability of monodisperse magnetic polymer particles.
AB  - A previously proposed method was examined for producing monodisperse,
      submicrometer-sized magnetic polymer particles. The method applies soap-free
      emulsion polymerization during which Fe3O4 magnetic nanoparticles are
      heterocoagulated onto precipitated polymer nuclei. To chemically fix the magnetic
      particles to the polymer nuclei, vinyl groups were introduced on the Fe3O4
      particles in a preliminary surface modification reaction with
      methacryloxypropyltrimethoxysilane, and methacryloxypropyldimethoxysilane (MPDMS)
      was added to reaction systems of the soap-free emulsion polymerization. The
      colloidal dispersion stability of magnetic polymer particles was improved by the
      addition of an ionic monomer, sodium p-styrenesulfonate (NaSS), during the
      polymerization. The polymerizations were carried out with styrene monomer and
      potassium persulfate initiator in ranges of NaSS concentrations (0-2.4 x 10(-3)
      M), NaSS addition times (60-80 min), and monomer concentrations (0.3-0.6 M) at
      fixed concentrations of 1.6 x 10(-2) M initiator and 1.3 x 10(-2) M MPDMS for pH
      4.5 adjusted with a buffer system of [CH3COOH]/[NaOH]. The addition of NaSS
      during the polymerization could maintain the dispersion stability of magnetic
      polymer particles during the polymerization. Selection of the reaction conditions
      enabled the preparation of colloidally stable, submicrometer-sized magnetic
      polymer particles that had coefficients of variation of distribution smaller than
      the standard criterion for monodispersity, 10%.

PMID- 16112227
TI  - An electrochemical quartz crystal impedance study on anti-human immunoglobulin G
      immobilization in the polymer grown during dopamine oxidation at an Au electrode.
AB  - The polymeric film grown during dopamine oxidation at an Au electrode was studied
      as a novel matrix for immobilizing anti-human immunoglobulin G (IgG) via the
      electrochemical quartz crystal impedance analysis (EQCIA) method. The growth of
      the polymeric films at Au electrodes during dopamine oxidation in neutral
      phosphate buffer (pH 7.4) and the immobilization of anti-human IgG into the
      polymeric films during their growth have been traced at real time. Lysozyme
      control experiments suggested that anti-human IgG was electrostatically
      incorporated into the polymeric film. Also, the porosity of the polymeric films
      has been discussed by measuring the "wet" and "dry" frequency shifts. Compared
      with a polypyrrole film immobilized with anti-human IgG, the proposed matrix
      possessed a larger amount of specific binding sites for human IgG by subsequent
      immunoreaction tests. The association constant of the anti-human IgG
      immunoreaction was obtained with satisfactory results.

PMID- 16112228
TI  - Free radical generation upon plasma treatment of cotton fibers and their
      initiation efficiency in surface-graft polymerization.
AB  - Low-temperature plasma was used to activate mercerized cotton fabrics, to be
      followed by grafting with various methacrylates. Careful analysis of the
      experimental electron spin resonance (ESR) lineshapes of cotton samples treated
      at different RF powers made it possible to recognize and quantify four different
      species of free radicals still persistent 30 h after irradiation in the samples
      maintained under inert atmosphere. The decay rate of these species at room
      temperature was also evaluated with the analysis of the time evolution of the ESR
      spectra. The nature of the free radical species actually involved in the monomer
      grafting reaction has been discussed for cotton fabrics prepared under different
      plasma treatment conditions by analyzing the ESR lineshapes.

PMID- 16112229
TI  - Vanadia-catalyzed solar photooxidation of aniline.
AB  - Vanadia photocatalyzes the oxidation of aniline to azobenzene in ethanol. The
      reaction was studied using natural sunlight and UV irradiation (365 nm) as a
      function of [aniline], catalyst loading, airflow rate, solvent composition, etc.
      The photocatalyst exhibits sustainable catalytic activity. The product formation
      is greater with illumination at 254 nm than at 365 nm. Electron donors such as
      triphenylphosphine, diphenylamine, and hydroquinone enhance the photocatalysis.
      The singlet oxygen quencher azide ion fails to inhibit the catalysis. The
      photocatalysis takes place in both protic and aprotic solvents. The mechanism of
      photocatalysis is discussed and the product formation analyzed using a kinetic
      model.

PMID- 16112230
TI  - Self-assembly prismatic aggregates formed during the calcination of ZnO powders:
      in situ monitoring by ETA technique and their photocatalytic properties.
AB  - This paper describes a unique phenomenon occurred during the calcination of ZnO
      powders, i.e., the ZnO particles self-assembled to form prismatic aggregates with
      a clear edges and faces. Field-emission scanning electron microscopy (FE-SEM) and
      X-ray diffraction (XRD) were used to characterize the particle morphology and
      crystal structure of the calcined sample. The emanation thermal analysis (ETA)
      technique was used to monitor the changes of ZnO particle surface and subsurface
      microstructure irregularities and the occurrence of interparticle compaction
      phenomena under in situ conditions of heating and cooling. It was assumed from
      the ETA results that the driven force of the self-assembly of ZnO particles
      towards prismatic aggregates originated from the solid state diffusion and
      migration of grain boundaries. The photocatalytic tests indicated that the
      prismatic aggregates of ZnO calcined at 800 degrees C demonstrated a highest
      photocatalytic activity for acetaldehyde decomposition because of the enhancement
      of the surface-exposed high-active crystal face of (101 0).

PMID- 16112231
TI  - Influence of various monovalent cations and calcium ion on the colloidal fouling
      potential.
AB  - The influence of various monovalent cations and of divalent calcium ions on
      colloidal fouling strength was investigated quantitatively on a bench-scale
      ultrafiltration device. A higher colloidal fouling potential (k) was consistently
      observed with lithium chloride compared to the same ionic strengths of chlorides
      of other monovalent cations (Na+, K+, and Cs+). This observation was attributed
      to the formation of an impervious layer around the colloidal particle by lithium
      ions that prevented the repulsive forces due to the interaction of the silica
      hairs formed on the particles in the presence of water. The impact of the
      divalent calcium ion on the fouling potential was more complex. The fouling
      potential first increased with calcium ion concentration and then decreased. The
      maximum value of fouling potential occurred at the ionic strength corresponding
      to the critical coagulation concentration, which decreased with increasing
      colloid concentration. The colloidal fouling potential was well correlated by a
      bilinear relationship with colloid concentration and ionic strength for all salts
      tested under the critical coagulation concentration.

PMID- 16112232
TI  - Hydrogen ion titration of alkyldimethylamine oxides by 13C and 1H NMR and
      conventional methods.
AB  - In the hydrogen ion titration of micelles, the degree of ionization of the
      micelle at a given pH has to be evaluated to obtain a pKa value of micelles (Ka
      being the proton dissociation constant) at the pH. We compared the degree of
      ionization obtained from 13C and 1H NMR spectra with that obtained from the
      stoichiometric method. We used dodecyldimethylamine oxide (C12DMAO) and
      hexyldimethylamine oxide (C6DMAO) to examine the titration behavior of micelles
      and monomers, respectively. We determined pKa values of amine oxides both in H2O
      and D2O. As to the monomer (C6DMAO), the degree of ionization from NMR,
      alpha(NMR), coincided with that from the conventional stoichiometric method
      alpha. The difference of pK1 of amine oxide monomer between D2O and H2O was about
      0.5: pK1(D) approximately pK1(H) + 0.5. The difference was about the same as that
      for carboxylic acids. As to the C12DMAO micelle, alphaNMR did not coincide with
      alpha over a considerable range of alpha. The NMR chemical shift might be
      influenced by micellar structure changes induced by the ionization, such as the
      sphere-to-rod transition. The intrinsic logarithmic dissociation constants of the
      micelle were 5.9+/-0.1 for H2O, and 6.5+/-0.1 for D2O.

PMID- 16112233
TI  - Preparation and characterization of new hybrid organic/inorganic systems derived
      from calcium (alpha-aminoalkyl)-phosphonates and -phosphonocarboxylates.
AB  - We have studied the phenomenon of calcium complexation by lab synthesized
      amphiphilic (alpha-aminoalkyl)-phosphonocarboxylic or -phosphonic acids. The
      electrical conductivity of aqueous solutions of sodium salts of all these acids
      was measured versus the volume of a calcium salt solution added. It appeared that
      calcium complexes are formed in a Ca/P atomic ratio close to 1. Calcium
      phosphonocarboxylates and calcium phosphonates were also precipitated by mixing
      aqueous solutions of disodium salts of phosphorus amphiphiles and calcium nitrate
      solutions. Before chemical analysis, these complexes were calcined to remove the
      organic part. In the mineralized products, calcium and phosphate were assayed:
      the Ca/P atomic ratio was equal to 1. X-ray diffraction and IR spectroscopy
      showed that they are made entirely of beta pyrophosphate (Ca2P2O7), a result in
      agreement with previous chemical analysis. The chemical formula of the starting
      calcium complexes could be written as CaL2H2O (L=ligand). The SEM micrographs of
      these complexes show plate-like structures. XRD patterns are characteristic of
      layered structures. These facts suggest that calcium complexes are composed of
      alternating bimolecular layers of calcium alkylphosphonocarboxylates or calcium
      alkylphosphonates, the chains being tilted and partially interdigitated.

PMID- 16112234
TI  - The importance of lipophobicity in surfactants: methods for measuring
      lipophobicity and its effect on the properties of two types of nonionic
      surfactant.
AB  - In researching the properties of surfactants, lipophobicity is an important
      consideration. Increasing surfactant lipophobicity corresponds to a decrease in
      the saturation concentration of a singly dispersed surfactant in oil, i.e., a
      decrease in the critical micelle concentration in oil (CMC(oil)). This, in turn,
      is the crucial property in discussing the efficiency of a surfactant.
      Lipophobicity is influenced by the structure and length of the hydrophilic moiety
      of the surfactant. Surfactants that consist of OH or CO groups are effective for
      use in both aliphatic and aromatic hydrocarbon-rich systems because they are
      highly lipophobic and of a compact size and function independent of temperature.
      These characteristics are also reflected in their phase behavior. Phase diagrams
      illustrate the following properties: temperature independence; strong absorption
      at the water-oil interface and efficient action even with a very small amount of
      surfactant with a low CMC; high solubilization of water and oil into an
      aggregated surfactant solution phase. Through phase diagrams, the CMC(oil) of
      R10EO8 was obtained and the result used to compare the many different
      characteristics of the more typical oxyethylene nonionic surfactants with the new
      polyglyceryl nonionic surfactants.

PMID- 16112235
TI  - Physicochemical studies on microemulsions 9. Conductance percolation of AOT
      derived W/O microemulsion with aliphatic and aromatic hydrocarbon oils.
AB  - Both volume- and temperature-induced percolation of conductance of w/o
      microemulsions formed with AOT in cyclic aliphatic and aromatic oils
      (cyclohexane, cyclohexanone, toluene, and xylenes), and volume percolation of
      water/AOT/oil systems using linear aliphatic hydrocarbons (n-hexane, n-heptane, n
      octane, i-octane, and n-decane) have been studied. The effect of additives, viz.
      sodium cholate (NaC), sodium deoxycholate (NaDC), cholesterol, n-butanol, and t
      butanol, toluene, and xylenes (o, m, and p) on the temperature-induced
      percolating processes using the oils cyclohexane and cyclohexanone has been
      examined. The percolation results have been analyzed in the light of scaling
      equation, and the energy of activation of the ion-transport phenomenon has been
      evaluated for both pre- and postpercolation stages. From the percolation data,
      the diameter of the microdispersed water droplets, their population, and surface
      area have been estimated. The enthalpy of dispersion of water in AOT/oil medium
      has been determined from isothermal titration calorimetric (ITC) measurements.

PMID- 16112236
TI  - Mixed micelles of series of monomeric and dimeric cationic, zwitterionic, and
      unequal twin-tail cationic surfactants with sugar surfactants: a fluorescence
      study.
AB  - Steady state fluorescence measurements have been carried out for binary mixtures
      of a series of monomeric cationic (MC), zwitterionic (ZI), dimeric cationic (DC),
      and twin-tail cationic (TC) surfactants with sugar (beta-C8G and beta-C12G) over
      the whole mole fraction range using pyrene as fluorescence probe. The cmc values
      thus determined for all the binary mixtures have been further evaluated using the
      regular solution theory. The various micellar parameters, such as micelle mole
      fraction (X1), regular solution interaction parameter (beta), micropolarity, and
      mean micelle aggregation number (Nagg), have been determined for all these series
      of mixtures. Variation in all these micellar parameters demonstrates that mixed
      micelles of these surfactants with beta-C8G are mostly synergistic in nature and
      the synergism increases with the increase in hydrophobicity of the cosurfactant
      in each case. The mixtures of beta-C12G with various cosurfactants do not show
      this behavior and instead of it, they show an increase in antagonism with the
      increase in hydrophobicity of cosurfactants. This discrepancy has been attributed
      to a large difference in hydrophobicity between beta-C8G and beta-C12G, and the
      chain folding of the latter is considered to be the reason for the antagonism.

PMID- 16112237
TI  - Area per surfactant molecule values of gemini surfactants at the liquid
      hydrophobic solid interface.
AB  - Areas per surfactant molecule at the liquid/hydrophobic solid (A(LS)) and the
      liquid/air (A(LA)) interface as a function of the spacer length are reported for
      cationic gemini surfactants having (CH2)n spacer s. A(LA) increases with
      increasing spacer length up to 6-8 CH2 groups in the spacer and then levels off.
      A(LS) values indicate a more closely packed arrangement of the surfactant
      molecules than that at the liquid/air interface. Comparison of A(LA) and A(LS)
      values indicates that the surfactant molecules at the liquid/hydrophobic solid
      interface are almost three times as closely packed as those at the liquid/air
      interface. A comparison of the experimental values of the area per surfactant
      molecule at both interfaces was made with those calculated from dimensions of the
      surfactant molecule in vacuo.

PMID- 16112238
TI  - Surfactant tail length-dependent lipase activity profile in cationic water-in-oil
      microemulsions.
AB  - The catalytic activity of Chromobacterium viscosum lipase (CV-lipase) was
      estimated across varying surfactant tail lengths (C-10-C-18) in water-in-oil
      (w/o) microemulsions of cationic surfactants containing four different
      hydroxyethyl-substituted head groups. An attempt to find a correlation, if any,
      between the activity of interfacially solubilized lipase and the varying
      surfactant tails was made for the first time in micellar enzymology. The second
      order rate constant, k2, in lipase-catalyzed hydrolysis of p-nitrophenyl-n
      hexanoate at pH 6.0 and 25 degrees C shows an improvement in enzyme activity
      (approximately 30-140%) across different head groups of amphiphiles with
      increasing tail lengths in varying solution compositions. Improvement of enzyme
      activity is prominent in ascending from C-10 to C-14/C-16, depending on the
      nature of polar head group. The hydrolytic activity of lipase in different
      surfactant (50 mM)/water/isooctane/n-hexanol with varying z=
      [alcohol]/[surfactant] (6.4 or 4.8) was amplified by 25-250% with increment in
      surfactant tail length in comparison with widely used cationic w/o microemulsions
      having solution compositions (z=16). As a notable outcome of this research, we
      found w/o microemulsions of 25 mM tetradecyltrimethylammonium
      bromide/water/isooctane/n-hexanol (z=8) producing the highest ever activity of
      lipase in any w/o microemulsions.

PMID- 16112239
TI  - Pancreatic exocrine and endocrine events occur concomitantly but independently
      during the course of fulminant type 1 diabetes.
AB  - Although pancreatic exocrine enzymes are often elevated in patients with
      fulminant type 1 diabetes, the onset of this elevation and its significance in
      disease development remain unclear. We therefore investigated the significance of
      elevated serum enzyme concentrations and pancreatic swelling in the development
      of fulminant type 1 diabetes. Serum pancreatic exocrine enzymes, including
      amylase, elastase-I, lipase and trypsin, were measured during the course of the
      disease in 11 patients with fulminant type 1 diabetes (3 men and 8 women; a range
      of age 24-73 years, median 33 years; a range of HbA1c at onset 4.5-6.7%, median
      6.0%), all of whom developed ketotic diabetes requiring intensive insulin therapy
      within a month. At least one pancreatic exocrine enzyme was elevated in each
      patient during the course of the disease. The concentration of enzymes on
      admission could not be correlated with urinary excretion of C-peptide. The time
      course of increase in serum amylase varied in these patients. In conclusion,
      neither the level of serum amylase nor the swelling of pancreas was associated
      with the onset or severity of fulminant type 1 diabetes. The pancreatic exocrine
      and endocrine events may occur concomitantly but independently during the course
      of fulminant type 1 diabetes.

PMID- 16112240
TI  - Relation of habitual snoring with components of metabolic syndrome in Korean
      adults.
AB  - AIMS: To examine the association between habitual snoring and components of the
      metabolic syndrome in Korean adults. Whether these associations are independent
      of obesity was also explored. METHODS: Four thousand five hundred and six men and
      5041 women aged 40-69 years from the Korean Health and Genome Study were
      examined. Information of snoring frequency was obtained by a questionnaire and
      components of the metabolic syndrome were measured. RESULTS: There was a clear
      dose-response relationship between the increasing frequency of snoring and the
      higher prevalence of each component of the metabolic syndrome (P<0.001). After
      adjustment for age, abdominal obesity, and the other metabolic components,
      hypertension was significantly associated with a 1.2-fold excess of habitual
      snoring in both men (P<0.05) and women (P<0.05). The association of habitual
      snoring with hypertension was unaltered by obesity. Regardless of the presence or
      absence of abdominal obesity, there was an increase in the prevalence of habitual
      snoring as the number of metabolic abnormalities increased. CONCLUSIONS: Habitual
      snoring is associated with hypertension independent of obesity. While the
      relationship between habitual snoring and obesity is well recognized,
      characterization of the role of the other components of the metabolic syndrome as
      a cause or result of habitual snoring warrants a further study.

PMID- 16112241
TI  - Long-term glycaemic control with insulin glargine in Type 2 diabetes.
AB  - OBJECTIVE: This study examined the long-term glycaemic control and safety of
      insulin glargine (LANTUS) in patients with Type 2 diabetes. STUDY DESIGN AND
      METHODS: This <or=28-month, long-term extension of a multinational, multicentre,
      open-label 52-week study enrolled patients from the original study to continue
      taking insulin glargine at bedtime plus previous oral hypoglycaemic agents
      (OHAs). Efficacy and safety were assessed by HbA(1c) and adverse events,
      symptomatic hypoglycaemia and selected clinical and laboratory variables.
      RESULTS: Two hundred and thirty-nine treated patients from the original study
      entered the extension study and 198 completed the extension study. There was a
      1.02% reduction in mean HbA(1c) from baseline of the original study (9.44%) to
      endpoint of the extension study (8.42%). No new or unexpected adverse events were
      observed with longer term exposure to insulin glargine over a treatment period
      of<or=39 months. Treatment-emergent adverse events were reported for 152 patients
      (63.6%), four of which (1.7%) were considered to be possibly treatment-related.
      Mean weight gain observed during the original study was +2.12 kg with an absence
      of further weight gain at the end of the extension study (+2.02 kg). CONCLUSION:
      Long-term insulin glargine treatment plus OHAs provides continued glycaemic
      control and is well tolerated in patients with Type 2 diabetes. Therefore,
      insulin glargine appears to be suitable for the long-term management of Type 2
      diabetes.

PMID- 16112242
TI  - A case of type 2 diabetes mellitus developing hypothyroidism discovered as a
      result of a discrepancy between glycated hemoglobin and glycated albumin values.
AB  - We report a case of type 2 diabetes mellitus presenting hypothyroidism due to
      overeating of seaweed that was noticed as a result of a discrepancy between
      glycated albumin (GA) and glycated hemoglobin (GHb). A 71-year-old woman was
      undergoing managed treatment with oral medicines and insulin for diabetes
      mellitus with no sign of thyroid disease. Her thyroid function was euthyroid
      without aid of thyroid hormone. All of the patient's thyroid autoantibodies were
      negative. Fifteen weeks prior to indications of hypothyroidism, she had started
      to consume large amounts (100-200 g dry weight equivalent) of cooked "wakame"
      seaweed every morning. Just before admission to our hospital, her GA was 26.9%,
      while GHb and fasting plasma glucose remained within normal ranges (less than
      5.6%, and 106 mg, respectively). This discrepancy between GA and GHb drew our
      attention to the development of complications. Naive interview of the patient led
      us to believe a thyroid hormone deficiency existed, though without any related
      complaints or findings, such as non-pitting edema, cold intolerance, or easy
      fatiguing. Seaweed consumption was stopped and periodic observation of thyroid
      function started. As thyroid hormone levels moved into normal range, GA and GHb
      returned to their normal relative ratio after 3 months. Thus, measurement of the
      relative ratio of GA and GHb may be useful for glycemic monitoring, with the
      potential as a readily available glycemic control marker for patients with
      changeable complications.

PMID- 16112243
TI  - High prevalence of obesity and associated risk factors in urban children in India
      and Pakistan highlights immediate need to initiate primary prevention program for
      diabetes and coronary heart disease in schools.

PMID- 16112244
TI  - Beneficial effect of lisinopril plus telmisartan in patients with type 2
      diabetes, microalbuminuria and hypertension.
AB  - Angiotensin-converting enzyme (ACE) inhibitors have favourable effects on
      hypertension and diabetic nephropathy, but persistent use may result in
      incomplete blockade of the renin-angiotensin system. Long-term effects of dual
      blockade using the ACE inhibitor lisinopril and the long-acting angiotensin II
      receptor blocker (ARB) telmisartan on blood pressure and albumin excretion rate
      (AER) were evaluated. Patients with type 2 diabetes mellitus, hypertension
      (systolic blood pressure [SBP] >or=140 mmHg or diastolic blood pressure [DBP]
      >or=90 mmHg) and microalbuminuria (AER 30-300 mg/24h) received 20mg of lisinopril
      or 80 mg of telmisartan once a day for 24 weeks. Patients were then randomised to
      continuing treatment with the respective monotherapy or with lisinopril plus
      telmisartan for a further 28 weeks. Significant (P<0.001) declines in SBP (11.1
      mmHg versus 10.0 mmHg), DBP (5.6 mmHg versus 5.3 mmHg) and AER (98 mg/24 h versus
      80 mg/24 h) were achieved with lisinopril (n=95) or telmisartan (n=97),
      respectively, after 24 weeks. Subsequent treatment with lisinopril plus
      telmisartan for 28 weeks resulted in further significant reductions (P<0.001) in
      SBP, DBP and AER compared with either monotherapy. All treatments were well
      tolerated. Lisinopril plus telmisartan thus provides superior blood pressure and
      AER control than either monotherapy. We conclude that use of dual blockade may
      provide a new approach to prevention of diabetic nephropathy in patients with
      type 2 diabetes, hypertension and microalbuminuria.

PMID- 16112245
TI  - The implementation of managed care for diabetes using medical informatics in a
      large Preferred Provider Organization.
AB  - BACKGROUND: It has been demonstrated by meta analysis that if a regular review of
      patients is guaranteed, the standard of primary care can be as good or better
      than hospital outpatient care, however, empirical data suggests that compliance
      with diabetes clinical practice recommendations is inadequate in primary care.
      This study describes the reorganization of diabetes care using disease management
      principles in a Preferred Provider Organization (PPO) operating on a country-wide
      basis in which each diabetes clinic became responsible for the overall care of
      all patients with diabetes. METHODS: This descriptive pre and post change study
      was undertaken in a large public-funded PPO insuring over one and half million
      individuals. The study was possible due the use of a centralized electronic
      disease registry which enabled the collection of all patient data. Several
      markers, such as HbA1C and LDC-cholesterol levels, were used to assess the
      quality of care for the diabetic patients. RESULTS: Mean HbA1C results of the
      cohort showed a continuous reduction from 8.1% (S.D. = 1.55) in 1999 to 7.68%
      (S.D. = 1.47) in 2002 and to 7.79 (S.D. = 1.54) in 2004. Improved results were
      also recorded for LDL-C 126.37 (S.D. = 35.16) in 1999 to 114.74 (S.D. = 34.49) in
      2002, and to 113.39 (S.D. = 33.8) in 2004. The number of diabetic patients seen
      by the diabetologist increased by 62% over this period, despite an increase in
      diabetologist work hours of only 23%. CONCLUSION: The reorganization of health
      delivery for diabetic patients within a country-wide PPO, based on the principles
      of disease management and supported by medical informatics improves quality of
      care.

PMID- 16112246
TI  - Should we biopsy each liver mass suspicious for hepatocellular carcinoma before
      liver transplantation?--yes.

PMID- 16112247
TI  - Differential contribution of hepatitis C virus NS5A and core proteins to the
      induction of oxidative and nitrosative stress in human hepatocyte-derived cells.
AB  - BACKGROUND/AIMS: We aimed to explore the effects of hepatitis C virus (HCV) core
      and NS5A proteins on reactive oxygen (ROS) and nitrogen species (RNS) formation
      and on gene expression profile of iNOS in human hepatocyte-derived cells.
      METHODS: Production of ROS and RNS and nitrotyrosine residues accumulation were
      determined by flow cytometry and fluorescent microscopy as well as by Western
      blot, respectively, in NS5A- and core-transfected cells. Northern blot, Western
      blot, real-time PCR, and luciferase assays were used to assess iNOS gene
      expression in both transfectants. RESULTS: Cytokine-activated NS5A- and core
      transfected cells induced ROS and RNS production but an earlier and more marked
      increase was observed in NS5A-expressing cells. Superoxide production was also
      augmented, showing a similar temporal pattern of appearance in both NS5A- and
      core-transfected cells. Although both NS5A and core HCV proteins were able to up
      regulate iNOS gene expression, accompanied by a nitrotyrosine-containing proteins
      accumulation, an earlier iNOS overexpression was observed in NS5A-expressing
      cells, suggesting a different time course of iNOS activation pattern for core and
      NS5A HCV proteins. CONCLUSIONS: Our results indicate a differential contribution
      of both HCV proteins to oxidative and nitrosative stress generation.

PMID- 16112248
TI  - Responsibility, fairness and rationing in health care.
AB  - OBJECTIVE: People make different choices about how to live their life and these
      choices have a significant effect on their health, the risks they face and their
      need for treatment in the future. The objective of this article is, drawing on
      normative political theory, to sketch an argument that assigns a limited but
      significant role to individual responsibility in the design of the health-care
      system. METHOD: In developing our argument, we proceed in five steps. First, we
      review the literature on criteria for priority setting. Second, we explore the
      most prominent contemporary tradition in normative theory, liberal egalitarian
      ethics, with the aim to clarify the role of responsibility for choice. In
      particular, we discuss where liberal egalitarian theories would draw the 'cut'
      between the responsibility of the state (which is extensive) and the
      responsibility of the individuals (which is limited but significant). In the
      third step, we identify a priority setting dilemma where the commonly advocated
      criteria would assign equal priority. Finally, we develop a simple model in order
      to examine the implications of introducing a well-defined notion of
      responsibility for choice in a priority-setting dilemma of this kind. RESULTS:
      Liberal egalitarianism holds individuals responsible for choices that affect
      their health, given that (i) the illness is completely or partly a result of
      individual behaviour and choice; (ii) the illness is not life-threatening; (iii)
      the illness does not limit the use of political rights or the exercise of
      fundamental capabilities; and (iv) the cost of treatment is low relative to the
      income of the patients. The paper shows how this type of considerations can be
      used to determine an optimal level of co-payments for diseases even when
      individual choices cannot be observed directly. CONCLUSIONS: It is possible to
      assign a limited but significant role to individual responsibility in the
      rationing of health-care resources. The liberal egalitarian argument captures a
      concern that is not captured by traditional criteria for priorities in health
      care. It can thus help policy makers in situations where the cost-effectiveness
      of different alternatives and the severity of the illnesses are approximately the
      same, or if the society wants to assign some weight to responsibility for choice.
      It can easily be linked to a system of graduated co-payments, but need not be.

PMID- 16112249
TI  - The economic burden of lung cancer and the associated costs of treatment failure
      in the United States.
AB  - The economic burden of lung cancer was examined with a retrospective case-control
      cohort study on a database containing inpatient, outpatient and drug claims for
      employees, dependents and retirees of multiple large US employers with wide
      geographic distribution. Patients were followed for maximum of 2 years from first
      cancer diagnosis until death, health benefits dis-enrollment or study end (31
      December 2000). Compared with controls (subjects without any cancer), patients
      with lung cancer (n = 2040) had greater health care service utilization and costs
      for hospitalization, emergency room visits, outpatient office visits, radiology
      procedures, laboratory procedures and pharmacy-dispensed drugs (all P < 0.05).
      Regression-adjusted mean monthly total costs were US dollar 6520 for patients
      versus US dollar 339 for controls (P < 0.0001), and overall costs across the
      study period (from diagnosis to death or maximum of 2 years) were US dollar
      45,897 for patients and US dollar 2907 for controls (P < 0.0001). The main cost
      drivers were hospitalization (49.0% of costs) and outpatient office visits (35.2%
      of costs). Monthly initial treatment phase costs (US dollar 11,496 per patient)
      were higher than costs during the secondary treatment phase (US dollar 3733) or
      terminal care phase (US dollar 9399). Failure of initial treatment was associated
      with markedly increased costs. Compared with patients requiring only initial
      treatment, patients experiencing treatment failure accrued an additional US
      dollar 10,370 per month in initial treatment phase costs and US dollar 8779 more
      per month after starting the secondary and/or terminal care phase. Over the
      course of the study period, these patients had total costs of US dollar 120,650,
      compared with US dollar 45,953 for those receiving initial treatment only. Thus,
      the incremental costs associated with treatment failure were US dollar 19,149 per
      month and US dollar 74,697 across the study period. Other types of clinical and
      epidemiological analysis are needed to identify risks for treatment failure. The
      economic burden of lung cancer on the US health care system is significant and
      increased prevention, new therapies or adjuvant chemotherapy may reduce both
      resource use and healthcare costs. New strategies for lung cancer that reduce
      hospitalizations and/or prevent or delay treatment failure could offset some of
      the economic burden associated with the disease.

PMID- 16112250
TI  - Modelling field-scale cadmium transport below the root zone of a sewage sludge
      amended soil in an arid region in Central Iran.
AB  - Addition of trace metals such as cadmium to soils in metal-rich sewage sludge may
      result in contamination of soil and groundwater. This study addresses the plot
      scale transport of Cd derived from sewage sludge in a layered clay soil in an
      arid region of central Iran. Sewage sludge was enriched by Cd at rates of 38 and
      80 mg kg(-1) and applied to experimental soil plots using a complete random block
      design with three replicates. Cadmium concentration was measured as a function of
      depth after 185 and 617 days. HYDRUS-1D and MACRO codes were calibrated for Cd
      transport in the site treated with 80 mg kg(-1) sewage sludge. Model parameters
      were estimated by inverse modelling using the SUFI-2 procedure. The site treated
      with 38 mg kg(-1) cadmium was used to test the calibrated models. Both convection
      dispersion equation (CDE) and non-equilibrium CDE in HYDRUS-1D produced
      reasonable calibration results. However, the estimated Freundlich sorption
      constants were significantly smaller than those measured in a batch study. A site
      tracer experiment revealed the existence of substantial macropore flow. For this
      reason we applied MACRO to account for this process. The calibration and test
      results with MACRO were as good as those obtained by HYDRUS-1D with the
      difference that adsorption constants were much closer to the measured ones. This
      indicates that in HYDRUS-1D, the adsorption parameters were underestimated in
      order to allow a deeper transport of Cd which had actually occurred due to
      macropore flow. A 20-year simulation scenario depicting the long-term effect of
      sludge application indicated small risk of groundwater contamination. However,
      high concentration of Cd near the soil surface raises a concern about the crop Cd
      uptake which should be further investigated.

PMID- 16112251
TI  - An array of genes implicated in Alzheimer's disease.
AB  - Studying altered gene expression patterns in Alzheimer's disease may be helpful
      for identifying novel therapeutic targets and for elucidating key cellular
      processes that are involved in the neurodegenerative phenotype. To date, the
      advances that have emerged from these types of studies have been limited, largely
      confirming prevailing hypotheses and pathways that have already been implicated
      in the disease process. The potential remains high, particularly when combined
      with proteomic approaches. In addition, the utilization of transgenic mouse
      models will no doubt also be of tremendous value for gene expression studies as
      they permit investigations at well-defined stages of pathology and cognitive
      function.

PMID- 16112252
TI  - [The palliative care in geriatrics: a retrospective study of 40 cases].
AB  - INTRODUCTION: Owing to the very great age and the polypathology of the patients
      in geriatrics, we are often confronted to the palliative care decision. PURPOSE:
      The purposes of this retrospective study were both to define the criteria leading
      to palliative care and to analyse the evolution of patients. METHOD: We analysed
      40 files of patients hospitalised in Geriatric internal medicine or Geriatric
      rehabilitation departments over 11 months. RESULTS: Mean age was 85.4 years and
      62.5% of patients were females. Infections, heart failure, general weakness,
      orthopaedic affections, strokes and cancers were the main causes of
      hospitalisation. Patients had 3 medical or surgical histories of chronic or cured
      serious diseases and a MMSE average value of 17.7. The rate of malnutrition was
      92% and 90% of patients were very dependent. Severe infections, cancers, heart
      failure and severe pressure ulcers were the main affections for decision of
      palliative care. The latter was always decided by the staff with patients or
      families taking part in 8 cases and being informed in other cases. The palliative
      care lasted 7 days on average. Morphine was used in 31 cases. No artificial
      nutrition was introduced. CONCLUSION: The decision of palliative care is very
      complex since great age, polypathology, great dependence and high prevalence of
      cognitive disorders are frequent in this population.

PMID- 16112253
TI  - Prevention of perinatal transmission of hepatitis B to babies at high risk: an
      evaluation.
AB  - We aimed to determine factors associated with successful vaccination coverage and
      development of infection in high-risk infants born to hepatitis B infected women.
      Immunisation of 860/932 (92%) of babies was started within 48 h of birth and
      three doses of vaccination completed for 794/921 (86%). Only 543 (58%) infants
      were tested and 26 (4.9%) were found to have evidence of current infection.
      Delayed start of immunisation was significantly associated with unbooked
      pregnancy, maternal hepatitis B e-markers and year. Current infection in the baby
      was strongly associated with maternal hepatitis B e-status, ethnicity and year of
      vaccination. The proportion of infants developing infection declined after 1998,
      coinciding with the publication of national recommendations and the wider use of
      the accelerated schedule.

PMID- 16112254
TI  - How increased pertussis vaccination coverage is changing the epidemiology of
      pertussis in Italy.
AB  - The epidemiology of pertussis in Italy is described by using data from the
      statutory notification system and from seroepidemiology studies. Starting from
      the 1990s, the incidence of pertussis in Italy has shown a sharp decline and is
      now at the lowest level ever reached. During this time period vaccination
      coverage has increased from 88% in 1998 to 95% in 2003. In 1996-97, the
      prevalence of subjects with levels of IgG antibodies against PT greater than
      2EU/ml was 77.6%. The increase in vaccination coverage will probably change the
      pattern of disease transmission and increase the number of susceptible adults,
      unless administration of booster doses to adolescents and adults is considered.

PMID- 16112255
TI  - Immunogenicity of one, two or three doses of a meningococcal C conjugate vaccine
      conjugated to tetanus toxoid, given as a three-dose primary vaccination course in
      UK infants at 2, 3 and 4 months of age with acellular pertussis-containing
      DTP/Hib vaccine.
AB  - Reduction of the number of injections necessary to confer protection in the
      infant schedule would reduce discomfort, improve cost-effectiveness and create
      space for the addition of new vaccinations in the future. This study assessed the
      immunogenicity of one, two or three doses of meningococcal C conjugate vaccine
      conjugated to tetanus toxoid (MCC-TT) [Neis-VacC] given concomitantly with a
      combined diphtheria/tetanus/acellular pertussis/Haemophilus influenzae type b -TT
      conjugate (DTaP-Hib-TT) [Infanrix-Hib] vaccine at 2, 3 and 4 months of age. A
      total of 106 healthy UK infants were enrolled and randomised into two groups, one
      in which blood was taken after the first and third dose and the other after the
      second and third dose. The meningococcal serogroup C serum bactericidal antibody
      (SBA) geometric mean titre (GMT) rose significantly from post-first dose (491,
      95% CI 275, 877) to post-second dose (1052, 95% CI 774, 1433) (p=0.03), with no
      significant change after the third dose (1024, 95% CI 768, 1366). An SBA titre of
      >or=8 was achieved by 92% after the first dose and 100% after the second and
      third doses. The Hib IgG geometric mean concentration (GMC) rose significantly
      after each dose: post-first (0.14 microg/ml 95% CI 0.10, 0.18), post-second (0.54
      microg/ml, 95% CI 0.33, 0.90), post-third (2.04 microg/ml, 95% CI 1.52, 2.74).
      The Hib GMC after the third dose was higher than reported previously when this
      DTaP/Hib was given either on its own or concomitantly with a MCC-CRM conjugate
      vaccine according to the UK 2, 3 and 4 month schedule. This suggests some
      enhancement of the response to a Hib-TT vaccine by concomitant administration of
      MCC-TT. These results suggest that a reduced number of doses of MCC-TT would be
      adequate in infancy if given concomitantly with an acellular pertussis-containing
      vaccine.

PMID- 16112256
TI  - Virulence-associated protein-specific serum immunoglobulin G-isotype expression
      in young foals protected against Rhodococcus equi pneumonia by oral immunization
      with virulent R. equi.
AB  - The purpose of this study was to determine whether foals immunized orally from 2
      days of age with virulent Rhodococcus equi developed a protective pulmonary
      immune response and to characterise the antibody response of the immunized foals
      to the virulence-associated proteins (Vaps) of the bacterium. Two groups of foals
      were used. One (n=4) was given live R. equi ATCC 33701 orally at 2, 7, and 14
      days of age. The second group comprised three non-immunized foals age-matched to
      the vaccinates. At 3 weeks of age, 1 week after the final immunization, both
      groups were challenged intrabronchially with virulent R. equi ATCC 33701 and
      observed for 2 weeks post-challenge. Unvaccinated foals became clinically
      pneumonic and had high fever with increased heart and respiratory rates and
      severe pneumonia evident at necropsy. Foals of the immunized group remained
      healthy and lung lesions were not found post-mortem. Thus, it is possible to
      immunize young foals orally to protect them by 3 weeks of age against lung
      challenge with R. equi, even in the presence of maternal antibodies. The antibody
      response of the immunized foals confirmed that VapA and VapC are highly
      immunogenic. The immunoglobulin G isotype-related serum antibody response of
      immunized compared to non-immunized foals had an IgGT bias and a relatively low
      IgGa:IgGb ratio, both features different from what has been previously observed
      in immune adults and immune foals. This suggests that the serum IgG isotype
      profile of antibody cannot be used as a measure of evidence of protection against
      R. equi pneumonia.

PMID- 16112257
TI  - Immunotherapy with CTL peptide and VSSP eradicated established human
      papillomavirus (HPV) type 16 E7-expressing tumors.
AB  - Peptide-based vaccines aimed at the induction of effective T-cell responses
      against established tumors have not been successful in clinic and require the use
      of new adjuvants. One of those is a new adjuvant in which gangliosides are
      incorporated into the outer membrane protein complex of Neisseria meningitidis to
      form very small size proteoliposomes (VSSP). In a preclinical model of human
      papillomavirus HPV16-induced cervical cancer we show that vaccination with HPV 16
      E7 derived minimal CTL peptide and VSSP protects mice against tumor challenge,
      induces regression of established tumors and produces E7-specific CD8+ T-cell
      responses.

PMID- 16112258
TI  - Towards a vaccine for attaching/effacing Escherichia coli: a LEE encoded
      regulator (ler) mutant of rabbit enteropathogenic Escherichia coli is attenuated,
      immunogenic, and protects rabbits from lethal challenge with the wild-type
      virulent strain.
AB  - The ler (LEE encoded regulator) gene product is a central regulator for the genes
      encoded on the locus of enterocyte effacement (LEE) pathogenicity island of
      attaching/effacing (A/E) pathogens, including human enteropathogenic E. coli
      (EPEC) and enterohemorrhagic E. coli (EHEC) as well as animal isolates. Although
      an in vivo role for Ler in bacterial virulence has not been documented, we
      hypothesized that a Ler deletion mutant should be attenuated for virulence but
      might retain immunogenicity. The goals of this study were to genetically
      characterize ler of a rabbit EPEC (rEPEC) strain (O103:H2), to examine the effect
      of ler on in vivo virulence, and to determine if intragastric inoculation of an
      attenuated rEPEC ler mutant was immunogenic and could protect rabbits against
      subsequent challenge with the wild-type virulent parent strain. The predicted ler
      gene product of rEPEC strain O103:H2 shares high homology (over 95% amino acid
      identity) with the Lers of another rEPEC strain RDEC-1 (O15:H-) and human EPEC
      and EHEC. A defined internal ler deletion mutant of rEPEC O103:H2 showed reduced
      production of secreted proteins. Although orogastric inoculation of rabbits with
      the virulent parent O103:H2 strain induced severe diarrhea, significant weight
      loss and early mortality with adherent mucosal bacteria found at sacrifice, the
      isogeneic ler mutant strain was well tolerated. Animals gained weight and showed
      no clinical signs of disease. Examination of histological sections of intestinal
      segments revealed the absence of mucosal bacterial adherence. This result
      demonstrates an essential role for Ler in in vivo pathogenicity of A/E E. coli.
      Single dose orogastric immunization with the rEPEC ler mutant induced serum IgG
      antibody to whole bacteria (but not to intimin). Immunized animals were protected
      against enteric infection with the WT virulent parent strain exhibiting normal
      weight gain, absence of diarrhea and absence of mucosally adherent bacteria at
      sacrifice. Such attenuated ler mutant strains may have potential for use as oral
      vaccines, or as vaccine vectors for delivery of foreign antigens. It remains to
      be determined whether such regulatory mutants can protect against infection with
      A/E bacteria of differing serotypes affecting different hosts.

PMID- 16112259
TI  - A space-time cluster of adverse events associated with canine rabies vaccine.
AB  - Electronic medical records of a large veterinary practice were used for
      surveillance of potential space-time clustering of adverse events associated with
      rabies vaccination in dogs. The study population was 257,564 dogs vaccinated in
      169 hospitals in 13 US metropolitan areas during a 24-month period. Using a scan
      statistic for population rate data, significant space-time clusters were
      identified involving the Atlanta and Tampa/St. Petersburg areas during a 4-month
      period. Separate spatial-temporal analyses of these cities using coordinates for
      individual address coordinates identified one significant patient cluster
      (P=0.002), associated with a 23.26 km-radius area in Atlanta (20 adverse events
      in 702 dogs; 2.85%) from November 2002 through February 2003. This percentage of
      adverse events was significantly increased after adjustment for host-related
      factors and the number of concurrent vaccinations.

PMID- 16112260
TI  - Citation on behalf of Simon N. Rogers on receipt of the BAOMS Surgery Prize 2004.

PMID- 16112261
TI  - Mandibular fractures: Historical perspective.
AB  - The principles of the treatment of mandibular fractures have changed recently,
      although the objective of re-establishing the occlusion and masticatory function
      remains the same. Splinting of teeth is an old way of immobilising fractures but
      the advent of modern biomaterials has changed clinical practice towards plating
      the bone and early restoration of function. We present a brief historical
      overview of techniques and systems that have been used for stabilisation of
      mandibular fractures.

PMID- 16112263
TI  - Neuroendocrine and behavioral development during puberty: a tale of two axes.
AB  - Puberty is marked by dramatic changes in neuroendocrine function. These changes
      have profound effects on the structure and function of the maturing nervous
      system, resulting in altered physiological and behavioral potentials in the adult
      organism. Indeed, the changes in neurobehavioral development during puberty rival
      those occurring during neonatal development. This review discusses the pubertal
      maturation of the hypothalamic-pituitary-gonadal and hypothalamic-pituitary
      adrenal axes; specifically, how the pubertal rise in gonadal hormones influences
      the development of various steroid-dependent motivated behaviors in adulthood, as
      well as the differences in stress reactivity in prepubertal and adult animals. We
      conclude that puberty represents another significant and perhaps critical period
      of neurobehavioral development. Furthermore, we suggest that perturbations of the
      developing nervous system during this period of maturation may result in
      deleterious outcomes in the future physiological and behavioral function of an
      individual on reaching adulthood.

PMID- 16112264
TI  - Regulation of oxytocin secretion.
AB  - A baby sucks at a mother's breast for comfort and, of course, for milk. Milk is
      made in specialized cells of the mammary gland, and for a baby to feed, the milk
      must be released into a collecting chamber from where it can be extracted by
      sucking. Milk "let-down" is a reflex response to the suckling and kneading of the
      nipple--and sometimes in response to the sight, smell, and sound of the baby--and
      is ultimately affected by the secretion of oxytocin. Oxytocin has many
      physiological roles, but its only irreplaceable role is to mediate milk let-down:
      oxytocin-deficient mice cannot feed their young; the pups suckle but no milk is
      let down, and they will die unless cross-fostered. Most other physiological roles
      of oxytocin, including its role in parturition, are redundant in the sense that
      the roles can be assumed by other mechanisms in the absence of oxytocin
      throughout development and adult life. Nevertheless, physiological function in
      these roles can be altered or impaired by acute interventions that alter oxytocin
      secretion or change the actions of oxytocin. Here we focus on the diverse stimuli
      that regulate oxytocin secretion and on the apparent diversity of the roles for
      oxytocin.

PMID- 16112265
TI  - Gonadotropin-releasing hormone: gene evolution, expression, and regulation.
AB  - The gonadotropin-releasing hormone (GnRH) gene is a superb example of the diverse
      regulation that is required to maintain the function of an evolutionarily
      conserved and fundamental gene. Because reproductive capacity is critical to the
      survival of the species, physiological homeostasis dictates optimal conditions
      for reproductive success, and any perturbation from this balance may affect GnRH
      expression. These disturbances may include alterations in signals dictated by
      stress, nutritional imbalance, body weight, and neurological problems; therefore,
      changes in other neuroendocrine systems may directly influence the hypothalamic
      pituitary-gonadal axis through direct regulation of GnRH. Thus, to maintain
      optimal reproductive capacity, the regulation of the GnRH gene is tightly
      constrained by a number of diverse signaling pathways and neuromodulators. In
      this review, we summarize what is currently known of GnRH gene structure, the
      location and function of the two isoforms of the GnRH gene, some of the many
      hormones and neuromodulators found to affect GnRH expression, and the molecular
      mechanisms responsible for the regulation of the GnRH gene. We also discuss the
      latest models used to study the transcriptional regulation of the GnRH gene, from
      cell models to evolving in vivo technologies. Although we have come a long way in
      the last two decades toward uncovering the intricacies behind the control of the
      GnRH neuron, there remain vast distances to cover before direct therapeutic
      manipulation of the GnRH gene to control reproductive competence is possible.

PMID- 16112266
TI  - Thyroid hormones and brain development.
AB  - The action of thyroid hormones (thyroxine, T4; triiodothyronine, T3) on brain
      development and function is gaining renewed interest. It has been known for many
      years that thyroid hormones are very important in mammalian brain maturation,
      influencing many aspects related to neural cell migration, differentiation, and
      signaling. In the last 10 years, genes regulated by thyroid hormones have been
      identified in the rodent brain, and understanding of the role of thyroid hormone
      nuclear receptors has been facilitated with the analysis of the phenotype of
      mutant mice for the different receptor isoforms. The general picture that emerges
      is that T4 and T3 may enter the brain through specific transporters. T4 is
      converted to the active hormone, T3, in glial cells, astrocytes, and tanycytes,
      although the main target cells are neurons and maturing oligodendrocytes. T3,
      acting through the nuclear receptors, controls the expression of genes involved
      in myelination, cell differentiation, migration, and signaling. In addition to
      transducing the T3 signal, the nuclear receptors also have activity in the
      unliganded state (i.e., as aporeceptors), mainly as repressors of transcription.
      The physiological meaning of aporreceptor action is not known, but they may play
      a role in the genesis of the hypothyroid phenotype. Among the questions that
      remain to be explored in more detail is the role of thyroid hormones and the T3
      receptors, both liganded and unliganded, in the fetal brain, especially before
      onset of fetal thyroid gland function. These questions are relevant for human
      health and the management of thyroid diseases during pregnancy.

PMID- 16112267
TI  - Estrogen signaling in the hypothalamus.
AB  - Estrogen has multifaceted effects on the hypothalamus that regulate a number of
      homeostatic functions including reproduction, temperature, energy balance,
      stress, and motivated behaviors. Estrogen targets all of the major hypothalamic
      neuroendocrine and autonomic cellular groups to activate multiple signaling
      pathways. Originally it was thought that all of these actions of estrogen could
      be ascribed to its binding to its "classical" intracellular receptor and to
      alterations in gene transcription. However, we now know that this steroid hormone
      activates multiple signaling pathways to affect neuronal excitability and gene
      transcription. Although the "classical" genomic signaling pathway has been
      recognized for almost half a century, until recently little attention has been
      paid to the rapid membrane-initiated signaling by estrogen in neurons. It has
      been known since the 1970s that estrogen can rapidly alter neuronal firing within
      seconds, indicating that some cellular effects of estrogen could occur via rapid,
      non-transcriptional mechanisms. Therefore, this chapter reviews the current
      status of estrogen signaling in the hypothalamus via membrane-initiated and
      nuclear-mediated events that affect the excitability of hypothalamic neurons and,
      ultimately, neuroendocrine and autonomic functions.

PMID- 16112269
TI  - Antiestrogens, aromatase inhibitors, and apoptosis in breast cancer.
AB  - Antiestrogens have been the therapeutic agents of choice for breast cancer
      patients whose tumors express estrogen receptors, regardless of menopausal
      status. Unfortunately, many patients will eventually develop resistance to these
      drugs. Antiestrogens primarily act by preventing endogenous estrogen from
      activating estrogen receptors and promoting cell growth, which can ultimately
      lead to tumor cell death. Understanding the mechanisms by which antiestrogens
      cause cell death or apoptosis is critical to our efforts to develop ways to
      circumvent resistance. This article focuses on antiestrogen-induced apoptosis
      both in vitro and in vivo. We review the clinical utility of both antiestrogens
      and aromatase inhibitors and their apoptogenic mechanisms in cell culture models.
      Among the key signaling components discussed are the roles of Bcl-2 family
      members, several cytokines, and their receptors, p53, nuclear factor kappa B
      (NFkappaB), IRF-1, phosphatidylinositol 3-kinase (PI3K)/Akt, and specific
      caspases. Finally, we discuss the evidence supporting a role for apoptotic
      defects in acquired and de novo antiestrogen resistance.

PMID- 16112268
TI  - Hormonal influences on cancer progression and prognosis.
AB  - Cell differentiation, proliferation, apoptosis, and cell motility are induced and
      regulated by a host of growth factors, vitamins, and hormones. The mode of
      function of these modifiers of biological response, the signaling pathways that
      they activate, and the interacting pathways that can influence the biological
      outcome have been the focus of attention. Especially recognized and discussed in
      this review is the deregulation of their function, leading to abnormalities in
      cell proliferation, alteration of intercellular adhesive cohesion, remodeling of
      the extracellular matrix, and invasive behavior and metastatic deposition that
      are so characteristic of tumor development and progression, which strongly
      underscores the concept of molecular progression of cancer constructed on the
      basis of the relationship between genetic changes and the biological events
      associated with cancer progression. The molecular changes associated with hormone
      and vitamin-driven responses and the deregulation of the expression and function
      of their target genes seem to correlate with specific biological events linked
      with cancer invasion and progression, and these findings could lead to the
      establishment of new markers of progression and to the development of new
      strategies for patient management. The scope of this work has been restricted by
      design and is dictated by the field of interest of the author's laboratory, but
      it is hoped that this field would be regarded adequately to reflect the wide
      genre of scientific interest in this field of human disease.

PMID- 16112270
TI  - Glucocorticoid receptor and heat shock factor 1: novel mechanism of reciprocal
      regulation.
AB  - Glucocorticoids control a host of bodily responses, ranging from carbohydrate
      metabolism in the liver to immunity and inflammation in the lymph system. In
      response to stress, glucocorticoid levels are known to rise-a response thought to
      provide a protective function against the stress event. It is now understood that
      the major function of glucocorticoids under stress is to protect not against the
      stress event itself but against overstimulation by host defenses (e.g.,
      inflammation). Control of these responses is achieved by the glucocorticoid
      receptor, a member of the steroid receptor transcription factor family. The
      oldest, most conserved, and most ubiquitous of the stress responses is induced
      expression of heat shock proteins that act as chaperones against stress-induced
      denaturation of protein. Expression of heat shock protein genes is controlled by
      heat shock transcription factor 1. In this work, we review our observations and
      those of other laboratories demonstrating a relationship between the
      glucocorticoid and heat shock responses. We show that complex but reciprocal
      mechanisms of regulation occur between glucocorticoid receptor and heat shock
      transcription factor 1 and present a model of coordinated action that likely
      serves to fully reestablish homeostasis following stress.

PMID- 16112271
TI  - C(19)-5-ene steroids in nature.
AB  - Dehydroepiandrosterone (DHEA), produced from cholesterol in the adrenals, is the
      most abundant steroid in our circulation. It is present almost entirely as the
      sulfate ester, but the free steroid is the form that serves as a precursor of
      estrogens and androgens, as well as 7- and 16-oxygenated derivatives. Mammalian
      tissues reduce the 17-keto Group of DHEA to produce androstenediol-a weak
      estrogen and full-fledged androgen. Its androgen activity is not inhibited by the
      anti-androgens commonly used to treat prostate cancer. It is probably responsible
      for the growth of therapy-resistant prostate cancer. DHEA is hydroxylated at the
      7 alpha position, and this derivative is oxidized by 11 beta-hydroxysteroid
      dehydrogenase to form 7-keto DHEA. The latter is reduced by the same
      dehydrogenase to form 7 beta-hydroxy DHEA. When fed to rats, each of the latter
      three steroids induce the formation of two thermogenic enzymes in the liver. The
      late-term human fetus produces relatively large amounts of 16 alphahydroxy DHEA,
      which serves the mother as a precursor of estriol.

PMID- 16112272
TI  - The androgen receptor: unlocking the secrets of its unique transactivation
      domain.
AB  - Whereas the androgen receptor (AR) protein shares similarities in the structure
      of its DNA- and hormone-binding domains with other members of the steroid nuclear
      receptor family, the molecule in its unliganded form has a seemingly unordered
      amino-terminal transactivation domain unique to the AR. A comprehensive
      understanding of the specific sub-structures and protein-protein interactions
      inherent to this domain in both its inactive and activated states remains un
      achieved. Therefore, the malleability of this peptide region in accommodating the
      diverse repertoire of transcription-modulating AR cofactors creates a great
      challenge for those intent on generating relevant three-dimensional molecular
      models. The AR transactivation domain achieves this flexibility through a series
      of conformational steps dependent on the presence of cofactors that induce
      allosteric changes, and thus has evolved several conserved peptide motifs
      representing key protein-protein interaction surfaces. Elucidation of these
      signaling regions, including their involvement in inducing AR transactivation
      domain structural changes, is of foremost interest in understanding how the AR
      achieves its pivotal role in regulating the androgen signaling axis particularly
      during the progression of prostate cancer.

PMID- 16112273
TI  - Cytokine recognition by human interleukin 5 receptor.
AB  - The activation of interleukin 5 (IL-5) receptor is a dynamic process that depends
      on specific interaction of IL-5 with IL-5 receptor alpha, the formation of
      oligomeric receptor complexes with receptor beta, and the initiation of
      cytoplasmic phosphorylation events. These steps culminate in the triggering of a
      cellular response. Important advances have been made recently in understanding
      the molecular mechanisms of cytokine recognition, receptor assembly, and signal
      triggering. Cytokine recognition can be envisioned by relating structure to
      function in IL-5 and IL-5 receptor alpha. A pair of charge-complementary regions
      plays an essential role in the specific interaction between IL-5 receptor alpha
      and IL-5. Moreover, peptide library methodology has led to the discovery of IL-5
      receptor alpha antagonists that mimic key elements in IL-5 receptor recognition.
      Because IL-5 has been implicated in the pathology of eosinophil-related
      inflammatory diseases, revealing the key recognition elements of IL-5, IL-5
      mimetic peptides, and IL-5 receptor alpha could help drive the design of new
      compounds for therapeutic treatment against allergic inflammatory diseases such
      as asthma.

PMID- 16112274
TI  - Leptin: structure, function and biology.
AB  - Leptin is an adipocyte-derived hormone that acts as a major regulator for food
      intake and energy homeostasis. Leptin deficiency or resistance can result in
      profound obesity, diabetes, and infertility in humans. Since its discovery, our
      understanding of leptin's biological functions has expanded from anti-obesity to
      broad effects on reproduction, hematopoiesis, angiogenesis, blood pressure, bone
      mass, lymphoid organ homeostasis, and T lymphocyte systems. Leptin orchestrates
      complex biological effects through its receptors, expressed both centrally and
      peripherally. Leptin receptor belongs to the class I cytokine receptor
      superfamily. At least five isoforms of leptin receptor exist, primarily because
      of alternate splicing. The longest form is capable of full signal transduction.
      The short forms may serve as leptin binding proteins and play a role in leptin
      transporting across the blood-brain barrier. In this review, we present the
      crystal structure of leptin and the structural comparison with other four-helical
      cytokines, discuss the leptin-receptor binding models based on other cytokine
      receptor complex structures, and summarize the most recent progress on leptin
      signal transduction pathways--especially its link to peripheral lipid metabolism
      through AMP-activated protein kinase and hepatic stearoyl-CoA desaturase-1
      pathways. Furthermore, we propose the structure based design of leptin analogs
      with increased stability, improved potency, enhanced blood-brain barrier
      transport, and extended time action for future therapeutic application.

PMID- 16112275
TI  - Leptin gene polymorphisms and their phenotypic associations.
AB  - In an era of rapidly increasing prevalence of human obesity and associated health
      problems, leptin gene polymorphisms have drawn much attention in biomedical
      research. Leptin gene polymorphisms have furthermore drawn much attention from
      animal scientists for their possible roles in economically important production
      and reproduction traits. Of the polymorphisms reported for exonic, intronic, and
      promoter regions of the leptin gene, 16 have been included in association studies
      in humans, 19 in cattle, and 6 (all exonic or intronic) in pigs. In humans,
      associations have been found with overweight or (early-onset) obesity, non
      insulin-dependent diabetes mellitus, prostate cancer, and non-Hodgkin's lymphoma.
      In cattle, associations have been found with feed intake, milk yield traits,
      carcass traits, and reproduction-related traits, and in pigs with feed intake,
      average daily gain, carcass traits (backfat/leanness), and reproduction
      performance traits. Many of the polymorphisms were only included in a limited
      number of association studies, or the phenotypes studied varied largely for a
      given polymorphism between studies. Therefore, many of the associations found for
      these polymorphisms need to be confirmed in future studies before firm
      conclusions can be drawn.

PMID- 16112276
TI  - Ghrelin, the same peptide for different functions: player or bystander?
AB  - Ghrelin is a recently discovered brain-gut peptide with two main physiological
      actions: growth hormone secretagogue activity and food intake inducer. Although
      its production is prevalently gastric, ghrelin is widely expressed in several
      tissues, where it might therefore act as a paracrine or autocrine factor. It is
      becoming clear that ghrelin is much more than a simple growth hormone
      secretagogue. In addition to its formerly envisaged role, ghrelin has other
      activities including stimulation of pituitary hormones secretion, modulation of
      food intake and control of energy metabolism, regulation of gastric and
      pancreatic activity, and cardiovascular and hemodynamic activities. In addition,
      modulation of cartilage and bone homeostasis, sleep and behavioral influences,
      and modulation of the immune system, as well as effects on cell proliferation,
      are other relevant actions of ghrelin. Thus, the peptide appears to be an
      important component of an integrated multifaceted regulatory system. In this
      review, we summarize several aspects of ghrelin biology and attempt to inform the
      reader with information regarding unexpected functions of this gastric peptide.

PMID- 16112279
TI  - Medical education in the UK: building a firm foundation.

PMID- 16112277
TI  - Cholecystokinin and adrenal-cortex secretion.
AB  - Cholecystokinin, or CCK, is a 33-amino acid peptide, originally considered a gut
      hormone, that acts via two subtypes of receptors, named CCK1-R and CCK2-R. CCK,
      along with its receptors, has been subsequently localized in the central nervous
      system, where it exerts, among other fuctions, antiorexinogenic actions. In this
      survey, we describe findings indicating that CCK, similar to other peptides
      modulating food intake (e.g., neuropeptide Y, leptin, and orexins), is also able
      to regulate the function of the hypothalamo-pituitary-adrenal axis, acting on
      both its central and peripheral branches. CCK stimulates aldosterone secretion
      via specific receptors (CCK1-Rs and CCK2-Rs in rats, and CCK2-Rs in humans)
      located in zona glomerulosa cells and coupled to the adenylate cyclase-dependent
      signaling cascade; and enhances glucocorticoid secretion from zona fasciculata
      reticularis cells via an indirect mechanism mainly involving the CCK2-R-mediated
      stimulation of corticotropin-releasing hormone-dependent ACTH release.

PMID- 16112278
TI  - Postoperative changes of carpal canal pressure in carpal tunnel syndrome: a
      prospective study with follow-up of 1 year.
AB  - Carpal canal pressures were measured in 103 patients with idiopathic carpal
      tunnel syndrome, before and after open release, with a postoperative follow-up of
      1 year. Twenty-five normal subjects were used as controls. Pressures were
      measured with the wrists in three positions: neutral, full passive flexion and
      full passive extension. At each wrist position, the mean pre-operative pressures
      in the study group were significantly higher than in the control group. In both
      groups, the pressures were maximal with full passive extension and minimal in the
      neutral wrist position. Immediately after surgical release, there was a marked
      decrease of the carpal canal pressures. However, during the second postoperative
      month, there was a significant increase of the pressures at each wrist position,
      although these were still within the normal control range. This rise in pressures
      persisted to 12 months. These findings suggest that the carpal ligament
      reconstitutes by normal scar formation, but with lengthening such that the volume
      of the carpal canal is enlarged, so preventing a rise in pressure with return of
      the pre-operative problem.

PMID- 16112280
TI  - Technology can make patients safer.

PMID- 16112281
TI  - Chocolate--more a food than a medicine.

PMID- 16112282
TI  - Surgical resection improves outcome in metastatic epidural spinal cord
      compression.

PMID- 16112283
TI  - Genetic susceptibility to bladder cancer.

PMID- 16112284
TI  - Neonatal hearing screens: Wessex re-visited.

PMID- 16112285
TI  - Role of the global civil society.

PMID- 16112286
TI  - Does a NEAT difference in energy expenditure lead to obesity?

PMID- 16112287
TI  - Health research: what's culture got to do with it?

PMID- 16112288
TI  - Rethinking lipid mediators.

PMID- 16112289
TI  - Fidgeting.

PMID- 16112291
TI  - Cerebral perfusion deficits in dysbaric illness.

PMID- 16112292
TI  - Cerebral perfusion deficits in dysbaric illness.

PMID- 16112295
TI  - Combination anti-hypertensives in WHO essential medicine list.

PMID- 16112297
TI  - Controlling the three "P"s in Africa.

PMID- 16112298
TI  - Adjuvant trastuzumab for HER2-positive breast cancer.

PMID- 16112299
TI  - Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute
      lymphoblastic leukaemia in first complete remission: comparison by genetic
      randomisation in an international prospective study.
AB  - BACKGROUND: The dismal prognosis of very-high-risk childhood acute lymphoblastic
      leukaemia could be improved by allogeneic haemopoietic cell transplantation. We
      compared this strategy with intensified chemotherapy protocols, with the aim to
      improve the outcome of children with very-high-risk acute lymphoblastic leukaemia
      in first complete remission. METHODS: A cooperative prospective study was set up
      in seven countries. Very-high-risk acute lymphoblastic leukaemia in first
      complete remission was defined by the presence of at least one of the following
      criteria: (1) failure to achieve complete remission after the first four-drug
      induction phase; (2) t(9;22) or t(4;11) clonal abnormalities; and (3) poor
      response to prednisone associated with T immunophenotype, white-blood-cell count
      of 100x10(9)/L or greater, or both. Children were allocated treatment by genetic
      chance, according to the availability of a compatible related donor, and assigned
      chemotherapy or haemopoietic-cell transplantation. The primary outcome was
      disease-free survival and analysis was by intention to treat. FINDINGS: Between
      April, 1995, and December, 2000, 357 children entered the study, of whom 280 were
      assigned chemotherapy and 77 related-donor haemopoietic-cell transplantation. 5
      year disease-free survival was 40.6% (SE 3.1) in children allocated chemotherapy
      and 56.7% (5.7) in those assigned transplantation (hazard ratio 0.67 [95% CI 0.46
      0.99]; p=0.02); 5-year survival was 50.1% (3.1) and 56.4% (5.9), respectively
      (0.73 [0.49-1.09]; p=0.12). INTERPRETATION: Children with very-high-risk acute
      lymphoblastic leukaemia benefit from related-donor haemopoietic-cell
      transplantation compared with chemotherapy. The gap between the two strategies
      increases as the risk profile of the patient worsens.

PMID- 16112300
TI  - Direct decompressive surgical resection in the treatment of spinal cord
      compression caused by metastatic cancer: a randomised trial.
AB  - BACKGROUND: The standard treatment for spinal cord compression caused by
      metastatic cancer is corticosteroids and radiotherapy. The role of surgery has
      not been established. We assessed the efficacy of direct decompressive surgery.
      METHODS: In this randomised, multi-institutional, non-blinded trial, we randomly
      assigned patients with spinal cord compression caused by metastatic cancer to
      either surgery followed by radiotherapy (n=50) or radiotherapy alone (n=51).
      Radiotherapy for both treatment groups was given in ten 3 Gy fractions. The
      primary endpoint was the ability to walk. Secondary endpoints were urinary
      continence, muscle strength and functional status, the need for corticosteroids
      and opioid analgesics, and survival time. All analyses were by intention to
      treat. FINDINGS: After an interim analysis the study was stopped because the
      criterion of a predetermined early stopping rule was met. Thus, 123 patients were
      assessed for eligibility before the study closed and 101 were randomised.
      Significantly more patients in the surgery group (42/50, 84%) than in the
      radiotherapy group (29/51, 57%) were able to walk after treatment (odds ratio 6.2
      [95% CI 2.0-19.8] p=0.001). Patients treated with surgery also retained the
      ability to walk significantly longer than did those with radiotherapy alone
      (median 122 days vs 13 days, p=0.003). 32 patients entered the study unable to
      walk; significantly more patients in the surgery group regained the ability to
      walk than patients in the radiation group (10/16 [62%] vs 3/16 [19%], p=0.01).
      The need for corticosteroids and opioid analgesics was significantly reduced in
      the surgical group. INTERPRETATION: Direct decompressive surgery plus
      postoperative radiotherapy is superior to treatment with radiotherapy alone for
      patients with spinal cord compression caused by metastatic cancer.

PMID- 16112301
TI  - NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results
      from the Spanish Bladder Cancer Study and meta-analyses.
AB  - BACKGROUND: Many reported associations between common genetic polymorphisms and
      complex diseases have not been confirmed in subsequent studies. An exception
      could be the association between NAT2 slow acetylation, GSTM1 null genotype, and
      bladder-cancer risk. However, current evidence is based on meta-analyses of
      relatively small studies (range 23-374 cases) with some evidence of publication
      bias and study heterogeneity. Associations between polymorphisms in other NAT and
      GST genes and bladder-cancer risk have been inconsistent. METHODS: We
      investigated polymorphisms in NAT2, GSTM1, NAT1, GSTT1, GSTM3, and GSTP1 in 1150
      patients with transitional-cell carcinoma of the urinary bladder and 1149
      controls in Spain; all the participants were white. We also carried out meta
      analyses of NAT2, GSTM1, and bladder cancer that included more than twice as many
      cases as in previous reports. FINDINGS: In our study, the odds ratios for bladder
      cancer for individuals with deletion of one or two copies of the GSTM1 gene were
      1.2 (95% CI 0.8-1.7) and 1.9 (1.4-2.7) respectively (p for trend <0.0001).
      Compared with NAT2 rapid or intermediate acetylators, NAT2 slow acetylators had
      an increased overall risk of bladder cancer (1.4 [1.2-1.7]) that was stronger for
      cigarette smokers than for never smokers (p for interaction 0.008). No
      significant associations were found with the other polymorphisms. Meta-analyses
      showed that the overall association for NAT2 was robust (p<0.0001), and case-only
      meta-analyses provided support for an interaction between NAT2 and smoking (p for
      interaction 0.009). The overall association for GSTM1 was also robust (p<0.0001)
      and was not modified by smoking status (p=0.86). INTERPRETATION: The GSTM1 null
      genotype increases the overall risk of bladder cancer, and the NAT2 slow
      acetylator genotype increases risk particularly among cigarette smokers. These
      findings provide compelling evidence for the role of common polymorphisms in the
      aetiology of cancer. RELEVANCE TO PRACTICE: Although the relative risks are
      modest, these polymorphisms could account for up to 31% of bladder cancers
      because of their high prevalence.

PMID- 16112302
TI  - Universal newborn screening for permanent childhood hearing impairment: an 8-year
      follow-up of a controlled trial.
AB  - An 8-year follow-up study of the birth cohort of babies enrolled in the Wessex
      controlled trial of universal newborn screening (UNS) for permanent childhood
      hearing impairment (PCHI) was undertaken to establish whether UNS would increase
      the proportion of all true cases of PCHI in children aged 7-9 years who are
      referred early. The proportion referred before 6 months of age increased from 11
      of 35 (31%) children with true PCHI born during periods without UNS to 23 of 31
      (74%) born during periods with UNS (difference 43%, 95% CI 19-60). UNS leads to
      early referral of PCHI.

PMID- 16112303
TI  - Obesity, cigarette smoking, and telomere length in women.
AB  - Obesity and smoking are important risk factors for many age-related diseases.
      Both are states of heightened oxidative stress, which increases the rate of
      telomere erosion per replication, and inflammation, which enhances white blood
      cell turnover. Together, these processes might accelerate telomere erosion with
      age. We therefore tested the hypothesis that increased body mass and smoking are
      associated with shortened telomere length in white blood cells. We investigated
      1122 white women aged 18-76 years and found that telomere length decreased
      steadily with age at a mean rate of 27 bp per year. Telomeres of obese women were
      240 bp shorter than those of lean women (p=0.026). A dose-dependent relation with
      smoking was recorded (p=0.017), and each pack-year smoked was equivalent to an
      additional 5 bp of telomere length lost (18%) compared with the rate in the
      overall cohort. Our results emphasise the pro-ageing effects of obesity and
      cigarette smoking.

PMID- 16112304
TI  - Phaeochromocytoma.
AB  - Phaeochromocytomas are rare neuroendocrine tumours with a highly variable
      clinical presentation but most commonly presenting with episodes of headaches,
      sweating, palpitations, and hypertension. The serious and potentially lethal
      cardiovascular complications of these tumours are due to the potent effects of
      secreted catecholamines. Biochemical testing for phaeochromocytoma is indicated
      not only in symptomatic patients, but also in patients with adrenal
      incidentalomas or identified genetic predispositions (eg, multiple endocrine
      neoplasia type 2, von Hippel-Lindau syndrome, neurofibromatosis type 1, and
      mutations of the succinate dehydrogenase genes). Imaging techniques such as CT or
      MRI and functional ligands such as (123)I-MIBG are used to localise biochemically
      proven tumours. After the use of appropriate preoperative treatment to block the
      effects of secreted catecholamines, laparoscopic tumour removal is the preferred
      procedure. If removal of phaeochromocytoma is timely, prognosis is excellent.
      However, prognosis is poor in patients with metastases, which especially occur in
      patients with large, extra-adrenal tumours.

PMID- 16112305
TI  - Buying results? Contracting for health service delivery in developing countries.
AB  - To achieve the health-related Millennium Development Goals, the delivery of
      health services will need to improve. Contracting with non-state entities,
      including non-governmental organisations (NGOs), has been proposed as a means for
      improving health care delivery, and the global experience with such contracts is
      reviewed here. The ten investigated examples indicate that contracting for the
      delivery of primary care can be very effective and that improvements can be
      rapid. These results were achieved in various settings and services. Many of the
      anticipated difficulties with contracting were either not observed in practice or
      did not compromise contracting's effectiveness. Seven of the nine cases with
      sufficient experience (greater than 3 years' elapsed experience) have been
      sustained and expanded. Provision of a package of basic services by contractors
      costs between roughly US3 dollars and US6 dollars per head per year in low-income
      countries. Contracting for health service delivery should be expanded and future
      efforts must include rigorous evaluations.

PMID- 16112306
TI  - End-of-life: a Hindu view.

PMID- 16112307
TI  - Benefits of experience--missing the perf.

PMID- 16112308
TI  - Placental site trophoblastic tumour arising from a partial hydatidiform mole.

PMID- 16112309
TI  - Injured rabbit ACL treated by radiofrequency. Effects of cyclic loading.
AB  - BACKGROUND: Radiofrequency treatment is increasingly used to treat shoulder
      instability. Patients are asked to restrain their physical activities after this
      treatment but there is no precise information concerning the necessity for the
      restrain. METHODS: There were two groups of ten specimens each. Treatment group
      specimens were stretched to subfailure injury, treated by a radiofrequency probe,
      and then cyclically loaded. Control group specimens were stretched to the same
      subfailure injury, Sham treated, and then cyclically loaded. Between each step of
      the experiment in both groups there was a relaxation test to examine the ligament
      viscoelastic properties. At the end, each ligament was stretched to failure and
      the load-elongation curve obtained. FINDINGS: Relaxation forces decreased after
      the subfailure injury in both groups (average 76% and 81% of intact state, in
      treatment and control groups, respectively). In the treatment group, the
      relaxation forces first increased after the radiofrequency treatment (average 99%
      of intact state), and then decreased after the cyclic loading (average 50% of
      intact state). The treated ligaments failed at lower loads and smaller
      deformations than the controls. INTERPRETATION: The radiofrequency treatment
      restored viscoelastic properties of the injured ligaments, but cyclic loading
      degraded these. Protection of the treated ligament is advised during the
      immediate post-operative period.

PMID- 16112310
TI  - Levels and distribution of organochlorine pesticides, polychlorinated biphenyls
      and polybrominated diphenyl ethers in sediments and biota from the Danube Delta,
      Romania.
AB  - Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl
      ethers (PBDEs) and organochlorine pesticides (OCPs), such as
      dichlorodiphenyltrichloroethane (DDT) and analogues, hexachlorocyclohexanes
      (HCHs) and hexachlorobenzene (HCB), were measured in sediments and biota
      (invertebrates, 11 fish species and cormorant tissues) collected in 2001 from the
      Danube Delta, the biggest European wetland. DDTs were the predominant pollutants
      in all samples. A high variability in the concentrations of pollutants within the
      same species was observed and this was related to sampling location, age, length
      and sex. DDTs were also the main organohalogenated contaminants in cormorant
      muscle and liver, followed by PCBs, HCHs, HCB and PBDEs. The present levels of
      DDTs in cormorant tissues are lower than levels measured in cormorant eggs
      sampled from the Danube Delta in 1982 and 1997, respectively. The variance of
      delta15N for herbivores was much greater than for carnivores, while carp and
      bream showed higher delta15N signatures than expected, probably due to a higher
      dietary proportion of benthos, typically more delta15N enriched relative to
      pelagic biota.

PMID- 16112311
TI  - The influence of single and multiple applications of pyrene on the evolution of
      pyrene catabolism in soil.
AB  - The influence of pyrene added in a single application (0, 50, 100 and 200 mg kg(
      1)) was investigated in multiple applications (1 x 50, 2 x 50 and 4 x 50 mg kg(
      1)) on the evolution of catabolic activity in a pristine pasture soil. The
      microbial community's ability to degrade pyrene was assessed at 0, 4, 8 and 12
      weeks by the mineralization of added 14C-pyrene. Significant mineralization (>5%)
      of added 14C-pyrene only occurred after 4 weeks soil-pyrene contact time in most
      of the pyrene-amended soils. Pyrene-amended soils showed statistically
      significantly shorter (P<0.05) lag times compared to the control soil after 8 and
      12 weeks soil-pyrene contact time. Further, the rates of degradation increased in
      the presence of pyrene, peaking at 8 weeks. In terms of the overall extents of
      pyrene mineralization, there were statistically significant increases (P<0.05)
      between 4 and 8 weeks, with little difference between 8 and 12 weeks, with the
      general trend that an increase in pyrene concentration resulted in higher levels
      of mineralization. Increasing the concentration and number of pyrene additions
      can have a significant impact on the adaptation of the soil microflora to degrade
      pyrene over time.

PMID- 16112312
TI  - Avoidance of low doses of naphthalene by Collembola.
AB  - The introduction of behavioural aspects of soil animals in ecological risk
      assessment would allow us to better assess soil quality, all the more if a range
      of animal populations are considered. We compared the avoidance behaviour of
      several strains of springtails (Arthropoda: Collembola) obtained from different
      soils. Naphthalene, a polycyclic aromatic hydrocarbon (PAH), widely represented
      in soils polluted with hydrocarbons, was tested in aqueous solutions on nine
      springtail species issuing from four sites. Fine quartz sand saturated with an
      aqueous solution of naphthalene was avoided by most of the tested species,
      avoidance being, however, detected down to a concentration of 0.030 mg L(-1).
      Folsomia candida (Isotomidae) was shown to be relatively tolerant to pollutants
      compared to other Collembola such as Mesaphorura macrochaeta, Mesaphorura yosii
      (Onychiuridae), Parisotoma notabilis (Isotomidae) and Arrhopalites caecus
      (Arrhopalitidae). Differences between strains could not be explained by
      properties of the original soils.

PMID- 16112313
TI  - Heavy metal speciation and phytotoxic effects of three representative sewage
      sludges for agricultural uses.
AB  - The environmental impact of sewage sludges depends on the availability and
      phytotoxicity of their heavy metal. The influence of representative sludges
      (dewatered anaerobic, pelletization, and composted sludge) on the availability of
      heavy metals, and their effects on seed germination were compared. The total
      heavy metal concentrations were below the maximum permitted for land-applied
      waste and the differences among them were small. The DTPA-extracted metal
      concentrations were rather different. The sequential extraction of the compost
      showed a slight increase in Cd and Cu availability, and a decrease in the
      availability of Fe, Mn, Ni and Zn. Pelletization increased the availability of Ni
      and slightly reduced that of Cr. The dewatering sludge led to greater
      availability of Cr and Mn but reduced the concentration of Cd. The three
      different sludges also affected seed germination and root elongation in different
      ways. The most serious adverse effects were caused by the dewatered sludge
      extract.

PMID- 16112314
TI  - Determination of potential sources of PCBs and PBDEs in sediments of the Niagara
      River.
AB  - Sediments from Niagara River, an important waterway connecting two of the Great
      Lakes (Lake Erie to Lake Ontario), were analyzed for 14 congeners of
      polychlorinated biphenyls (PCBs) and 9 congeners of polybrominated diphenyl
      ethers (PBDEs) using accelerated solvent extraction and gas chromatography/mass
      spectrometry. Total concentrations of PCBs ranged from 1.7 to 124.6 ng/g were
      PCBs 138 and 153 were found in all samples. All sites but one showed PBDE in
      sediments with total concentrations as high as 148 ng/g, suggesting that PBDE is
      becoming an important class of POP. A land-use and coverage map was used to trace
      potential localized sources of PCB and PBDE contamination. Results indicate that
      the highest levels of PCBs and PBDEs were found in sediments collected from areas
      closest to the discharge locations of municipal wastewater treatment plants
      (WWTP) and local industries. This is the first study that suggests the importance
      of WWTP discharges as a potential source of PBDE contamination in the Great
      Lakes.

PMID- 16112316
TI  - Assessing the effects of environmental toxicant exposure in developmental
      epidemiological studies: issues for risk assessment.
AB  - Epidemiological studies have been of critical importance to the understanding of
      the effects of environmental chemical exposure during development on the behavior
      of infants and children. The ultimate goal of these studies should be to provide
      information that may be used directly for the protection of public health. The
      strategies for the assessment endpoints include development of domain-specific
      tests based on knowledge concerning effects of the chemicals being assessed, or
      use of standard clinical instruments that sample a range of functions. Discussion
      of an overall strategy for choice of endpoints would allow more straightforward
      comparisons across studies. There is increasing recognition of the importance of
      measuring a number of chemicals relevant to the population under study; however,
      different investigators make different decisions concerning which and how many
      chemicals to measure, as well as how to include them in the statistical analysis,
      particularly when there is a high degree of collinearity. Chemicals that are
      highly correlated with the "chemical of interest" are sometimes not included in
      the statistical analysis, resulting in missed opportunity to derive important
      information from the study. In addition, the shape of the relationship between
      exposure and effect is usually not explored in epidemiological studies, even
      though such information is critical for risk assessment. Opportunity for
      discussion among investigators, statisticians, and risk assessors potentially
      would result in human developmental toxicity studies being maximally useful for
      public health decisions.

PMID- 16112317
TI  - Studying toxicants as single chemicals: does this strategy adequately identify
      neurotoxic risk?
AB  - Despite the fact that virtually all chemicals exposure of humans are to mixtures,
      and that these mixed exposures occur in the context of numerous other risk
      modifiers, our current understanding of human health risks is based almost
      entirely on the evaluation of chemicals studied in isolation. This paper
      describes findings from our collaborative studies that prompt questions about
      these approaches in the context of neurotoxicology. The first section describes
      studies investigating the interactions of maternal Pb exposure with maternal
      stress. Examined across a range of outcome measures, it shows that maternal Pb
      can modulate the effects of maternal stress, and, conversely, stress modifies the
      effects of Pb. Further, effects of Pb+stress could be detected in the absence of
      an effect of either risk factor alone, and, moreover, the profile of effects of
      Pb alone differs notably from that of Pb+stress. Collectively, interactions were
      not systematic, but differed by brain region, gender and outcome measure. A
      second section describes outcomes of studies examining combined exposures to the
      pesticides paraquat (PQ) and maneb (MB) during development which likewise reveal
      potentiated effects of combined exposures. They also demonstrate examples of both
      progressive and cumulative neurotoxicity, including a marked vulnerability
      following gestational exposure to MB, to the effects of PQ, a pesticide with no
      structural relationship to MB. The ability of current hazard identification and
      risk assessment approaches to adequately identify and encompass such effects
      remains an important unanswered question. One consideration proposed for further
      evaluating potential interactions that may be of significance for the nervous
      system is based on a multi-hit hypothesis. It hypothesizes that the brain may
      readily compensate for the effects of an individual chemical itself acting on a
      particular target system, but when multiple target or functional sites within
      that one system are attacked by different mechanisms (i.e., multiple chemical
      exposures or chemical exposures combined with other risk factors), homeostatic
      capabilities may be restricted, thereby leading to sustained or cumulative
      damage.

PMID- 16112318
TI  - Ethical, legal, and social issues: our children's future.
AB  - A convergence of issues suggests that protecting child health is not so much a
      matter of research, but rather a matter of policy and advocacy. First, we have
      well-articulated views of a vision for child health. Second, we have experience
      and toxicological research findings demonstrating the adverse health effects of
      hazardous chemicals on children and recognize that children are more sensitive
      than adults to chemical exposures. Results from toxicology research have
      motivated many regulatory and legal actions, and public policy decisions,
      including the banning of some pesticides, reducing exposures in the workplace,
      and lowering of acceptable blood lead levels in children. We also know that
      childhood disabilities from chemical exposure during developmental are often not
      treatable and therefore must be prevented. Finally, we have an increasingly well
      defined framework for discussing social and ethical responsibility to our
      children. New discoveries in the basic biological and toxicological sciences have
      challenged our bioethical thinking and societal decision-making. This paper will
      explore the ethical, legal, and social issues raised by the toxicological
      sciences first by examining some hard lesson learned about childhood effects of
      chemicals and then by examining the difficult policy and research decisions that
      must be made as we address our need for additional information about the health
      effects of chemicals on adults and children and the impact of having this
      information. The precautionary principle will be considered as an alternative
      decision-making approach as well as exploring the concept of the citizen
      toxicologist (CT). As Garrett Hardin pointed out many years ago, the problems we
      face often have no technical solutions, but rather require a policy-based
      approach. This paper will be of interest to the public and health professionals
      concerned about the broader impact of toxicological research on bioethical and
      societal decision-making.

PMID- 16112319
TI  - Concentrations of environmental chemicals associated with neurodevelopmental
      effects in U.S. population.
AB  - Humans are exposed to many environmental chemicals, some of which can potentially
      affect neurodevelopment. Fetuses, infants, and young children are the most
      susceptible to the effects of these chemicals. As part of the National Health and
      Examination Survey, 1999-2000, the Centers for Disease Control and Prevention
      analyzed biological samples for many of these chemicals in a representative
      sampling of the U.S. population. Concentration data of selected metals,
      persistent organic pollutants, organophosphorus and carbamate insecticides, and
      cotinine are presented. For example, the 95th percentile estimates for serum
      total PCBs (whole weight) in the population aged 20 years and older is about 2.7
      ng/g. The 95th percentile estimates for serum dioxin total toxic equivalence in
      the U.S. population aged 20 years and older is between 40 and 50 pg/g lipid
      basis. In general, human levels of these chemicals are decreasing over time in
      the U.S. population. This reflects the effects of legislation, industry efforts,
      and changes in lifestyle/activity patterns in the U.S. population. These data
      will continue to be collected in 2-year cycles and thus allow changes in human
      levels to be followed.

PMID- 16112320
TI  - Characterizing children's exposures: beyond NHANES.
AB  - Biomonitoring programs, such as those being conducted at the Centers for Disease
      Control and Prevention in conjunction with the National Health and Nutrition
      Examination Survey (NHANES), are of benefit to all disciplines of environmental
      public health. However, all programs have limitations, and like most things in
      science, "One size does not fit all." We point out some of these limitations,
      particularly those dealing with the amount of biological sample available from
      various age groups and the specificity of the exposure assessment. We recommend
      additional studies to supplement the NHANES biomonitoring data.

PMID- 16112321
TI  - Volcano related atmospheric toxicants in Hilo and Hawaii Volcanoes National Park:
      implications for human health.
AB  - Volcanic fog (vog) from Kilauea volcano on the island of Hawaii includes a
      variety of chemical species including sulfur compounds and traces of metals such
      as mercury. The metal species seen tended to be in the nanograms per cubic meter
      range, whereas oxides of sulfur: SO2 and SO3 and sulfate aerosols, were in the
      range of micrograms per cubic meter and rarely even as high as a few milligrams
      per cubic meter of air (nominally ppb to ppm). These sulfur species are being
      investigated for associations with both acute and chronic changes in human health
      status. The sulfate aerosols tend to be less than 1 microm in diameter and tend
      to dominate the mass of this submicron size mode. The sulfur chemistry is
      dynamic, changing composition from predominantly sulfur dioxide and trioxide
      gasses near the volcano, to predominantly sulfate aerosols on the west side of
      the island. Time, concentration and composition characteristics of submicron
      aerosols and sulfur dioxide are described with respect to the related on-going
      health studies and public health management concerns. Exposures to sulfur dioxide
      and particulate matter equal to or less than 1 microm in size were almost always
      below the national ambient air quality standards (NAAQS). These standards do not
      however consider the acidic nature and submicron size of the aerosol, nor the
      possibility of the aerosol and the sulfur dioxide interacting in their toxicity.
      Time series plots, histograms and descriptive statistics of hourly averages give
      the reader a sense of some of the exposures observed.

PMID- 16112322
TI  - Volumetric neuroimaging and low-dose early-life exposures: loose coupling of
      pathogenesis-brain-behavior links.
AB  - The interface of developmental neuroimaging with developmental neurotoxicology
      can, broadly speaking, address two complementary concerns. The first is to study
      the impact of specific exposures on brain development. The second is to study
      known neurobehavioral disorders with an eye to discerning toxicological
      contributions to pathogenesis. Pathogenesis targets brain based upon physical
      properties (receptors, growth factors, etc.) while behavior is modulated by
      regional and neural systems alterations. The distribution of pathogenesis-brain
      relationships overlaps only partially with that of brain-behavior relationships.
      The goal of this paper is to highlight methodological issues involved in
      designing and interpreting volumetric neuroimaging studies in the light of this
      loose coupling.

PMID- 16112324
TI  - Neurobehavioral performance in preschool children from agricultural and non
      agricultural communities in Oregon and North Carolina.
AB  - Organophosphate (OP) pesticides produce acute toxic effects but little is known
      about low-level chronic exposures. Latino children of agricultural workers have a
      high risk of exposure to pesticides because of the close proximity of their homes
      to fields where pesticides are applied and from take-home exposure.
      Neurobehavioral performance of preschool children from agricultural (AG)
      communities was compared to performance of those from non-agricultural (Non-AG)
      communities in Oregon and North Carolina. Seventy-eight children aged 48-71
      months completed a battery of neurobehavioral tests two times, approximately 1
      month apart. Multiple regression revealed that the AG children performed poorer
      on measures of response speed (Finger Tapping) and latency (Match-to-Sample)
      compared to the Non-AG children. These results demonstrate modest differences in
      AG children compared to Non-AG children that are consistent with functional
      effects seen in adults exposed to low concentrations of OP pesticides. Just as
      was the case following early research on adults poisoned by pesticides, this
      study points to the need for additional investigations to test the hypothesis
      that low-concentration OP exposures affect acquisition of test performance,
      response speed and latency in children of agricultural workers.

PMID- 16112323
TI  - A summary of recent findings on birth outcomes and developmental effects of
      prenatal ETS, PAH, and pesticide exposures.
AB  - Inner-city minority populations are high-risk groups for adverse birth outcomes
      and also more likely to be exposed to environmental contaminants, including
      environmental tobacco smoke (ETS), benzo[a]pyrene B[a]P, other ambient polycyclic
      aromatic hydrocarbons (global PAHs), and residential pesticides. The Columbia
      Center for Children's Environmental Health (CCCEH) is conducting a prospective
      cohort study of 700 northern Manhattan pregnant women and newborns to examine the
      effects of prenatal exposure to these common toxicants on fetal growth, early
      neurodevelopment, and respiratory health. This paper summarizes results of three
      published studies demonstrating the effects of prenatal ETS, PAH, and pesticides
      on birth outcomes and/or neurocognitive development [Perera FP, Rauh V, Whyatt
      RM, Tsai WY, Bernert JT, Tu YH, et al. Molecular evidence of an interaction
      between prenatal environment exposures on birth outcomes in a multiethnic
      population. Environ Health Perspect 2004;12:630-62; Rauh VA, Whyatt RM, Garfinkel
      R, Andrews H, Hoepner L, Reyes A, et al. Developmental effects of exposure to
      environmental tobacco smoke and material hardship among inner-city children.
      Neurotoxicol Teratol 2004;26:373-85; Whyatt RM, Rauh V, Barr DB, Camann DE,
      Andrews HF, Garfinkel R, et al. Prenatal insecticide exposures, birth weight and
      length among an urban minority cohort. Environ Health Perspect, in press]. To
      evaluate the effects of prenatal exposure to ETS, PAHs, and pesticides,
      researchers analyzed questionnaire data, cord blood plasma (including biomarkers
      of ETS and pesticide exposure), and B[a]P-DNA adducts (a molecular dosimeter of
      PAHs). Self-reported ETS was associated with decreased head circumference (P =
      0.04), and there was a significant interaction between ETS and adducts such that
      combined exposure had a significant multiplicative effect on birth weight (P =
      0.04) and head circumference (P = 0.01) after adjusting for confounders. A second
      analysis examined the neurotoxic effects of prenatal ETS exposure and postpartum
      material hardship (unmet basic needs in the areas of food, housing, and clothing)
      on 2-year cognitive development. Both exposures depressed cognitive development
      (P < 0.05), and there was a significant interaction such that children with
      exposure to both ETS and material hardship exhibited the greatest cognitive
      deficit (7.1 points). A third analysis found that cord chlorpyrifos, and a
      combined measure of cord chlorpyrifos, diazinon, and propoxur-metabolite, were
      inversely associated with birth weight and/or length (P < 0.05). These results
      underscore the importance of policies that reduce exposure to ETS, air pollution,
      and pesticides with potentially adverse effects on fetal growth and child
      neurodevelopment.

PMID- 16112325
TI  - Maternal-fetal distribution of manganese in the rat following inhalation exposure
      to manganese sulfate.
AB  - Studies examining the pharmacokinetics of manganese during pregnancy have largely
      focused on the oral route of exposure and have shown that the amount of manganese
      that crosses the rodent placenta is low. However, limited information exists
      regarding the distribution of manganese in fetal tissues following inhalation.
      The objective of this study was to determine manganese body burden in CD rats and
      fetuses following inhalation of a MnSO4 aerosol during pregnancy. Animals were
      evaluated following pre-breeding (2 weeks), mating (up to 14 days) and
      gestational (from gestation day (GD) 0 though 20) exposure to air or MnSO4 (0.05,
      0.5, or 1 mg Mn/m(3)) for 6h/day, 7 days/week. The following maternal samples
      were collected for manganese analysis: whole blood, lung, pancreas, liver, brain,
      femur, and placenta. Fetal tissues were examined on GD 20 and included whole
      blood, lung, liver, brain, and skull cap. Maternal lung manganese concentrations
      were increased following exposure to MnSO4 at >or=0.05 mg Mn/m(3). Maternal brain
      and placenta manganese concentrations were increased following exposure of
      pregnant rats to MnSO4 at >or=0.5 mg Mn/m(3). Increased fetal liver manganese
      concentrations were observed following in utero exposure to MnSO4 at >or=0.5 mg
      Mn/m(3). Manganese concentrations within all other fetal tissues were not
      different from air-exposed controls. The results of this study demonstrate that
      the placenta partially sequesters inhaled manganese, thereby limiting exposure to
      the fetus.

PMID- 16112326
TI  - Neurological impairment in fetal mouse brain by drinking water disinfectant
      byproducts.
AB  - Developmental exposure to environmental chemicals may have detrimental effects on
      embryonic brains that could play a major role in the etio-pathology of fetal and
      adult neurological diseases. The exact mechanism by which prenatal exposures to
      environmental agents, such as drinking water disinfectant byproducts (DBP), cause
      neurological impairment in fetus is not known. Our objective is to examine the
      impact of prenatal exposure to DBP on fetal brain development. Pregnant CD-1
      mice, at the sixth day of gestation (GD-6), received a daily (GD-6-GD-18) oral
      dose of chloroacetonitrile (CAN, 25 ppm), a member of DBP. To assess fetal brain
      uptake of CAN, several animals were injected with a tracer dose of 2-[(14)C]-CAN
      (333 microCi/kg, i.v.), at GD-12 and processed for quantitative in situ micro
      whole-body autoradiography (QIMWBA) at 1 and 24 h after treatment. The remaining
      animals continued receiving CAN until GD-18 when fetal brains were processed for
      biochemical determination of oxidative stress (OS) or prepared for histological
      examinations. The results indicate a rapid placental transfer and fetal brain
      uptake of 2-[(14)C]-CAN/metabolites in cortical areas and hippocampus. In treated
      animals 3-fold decrease in glutathione (GSH), 1.3-fold increase in lipid
      peroxidation and 1.4-fold increase in DNA oxidation were detected as compared to
      control. DeOlmos cupric silver staining of fetal brains indicated significant
      increase in cortical neurodegeneration in treated animals. Immunohistochemical
      labeling (TUNEL) of apoptotic nuclei in the cortices and choroid plexuses were
      also increased in treated animals as compared to control. In conclusion, CAN
      crosses the placental and fetal blood-brain barriers and induces OS that
      triggered apoptotic neurodegenration in fetal brain. Future studies will examine
      the molecular mechanisms of these events and its impact on neural development of
      offspring.

PMID- 16112327
TI  - Role of paraoxonase (PON1) status in pesticide sensitivity: genetic and temporal
      determinants.
AB  - Individual differences in detoxication capacities for specific organophosphorous
      (OP) compounds are due largely to differences in catalytic efficiency or
      abundance of the HDL-associated enzyme, paraoxonase (PON1). First, we provide
      evidence that children less than 2 years of age represent a particularly
      susceptible population for OP exposure due to low abundance of PON1 and variable
      onset of plasma PON1 activity. Second, we describe studies examining the
      neurotoxic effects of chronic, low-level OP pesticide exposure in mice. PON1
      knockout (PON1(-/-)) and wild-type mice were exposed chronically (PN4 to PN21) to
      low levels of chlorpyrifos oxon (CPO). Endpoints included cholinesterase
      activity, histopathology, gene expression, and behavior. Even at PN4, when PON1
      levels were low in wild-type mice, PON1(-/-) mice were more sensitive to
      inhibition of brain cholinesterase by CPO. At PN22, and persisting as long as 4
      months, chronic developmental exposure to 0.18 mg/kg/d or 0.25 mg/kg/d CPO
      resulted in perinuclear vacuolization of cells in a discrete area of the
      neocortex and irregular distribution of neurons in the cortical plate, with an
      increase in the number of affected cells at 0.25mg/kg/d. Third, we describe a
      transgenic mouse model in which human transgenes encoding either hPON1Q192 or
      hPON1R192 were expressed at equal levels in place of mouse PON1. The
      developmental onset of expression followed the mouse time course and was
      identical for the two transgenes, allowing these mice to be used to assess the
      importance of the Q192R polymorphism during development. Adult mice expressing
      hPON1R192 were significantly more resistant than hPON1Q192 mice to CPO toxicity.
      Our studies indicate that children less than 2 years old, especially those
      homozygous for PON1Q192, would be predicted to be particularly susceptible to CPO
      toxicity.

PMID- 16112328
TI  - Dieldrin-induced neurotoxicity: relevance to Parkinson's disease pathogenesis.
AB  - Parkinson's disease (PD) is increasingly recognized as a neurodegenerative
      disorder strongly associated with environmental chemical exposures. Recent
      epidemiological data demonstrate that environmental risk factors may play a
      dominant role as compared to genetic factors in the etiopathogenesis of
      idiopathic Parkinson's disease. Identification of key genetic defects such as
      alpha-synuclein and parkin mutations in PD also underscores the important role of
      genetic factors in the disease. Thus, understanding the interplay between genes
      and environment in PD may be critical to unlocking the mysteries of this 200-year
      old neurodegenerative disease. Pesticides and metals are the most common classes
      of environmental chemicals that promote dopaminergic degeneration. The
      organochlorine pesticide dieldrin has been found in human PD postmortem brain
      tissues, suggesting that this pesticide has potential to promote nigral cell
      death. Though dieldrin has been banned, humans continue to be exposed to the
      pesticide through contaminated dairy products and meats due to the persistent
      accumulation of the pesticide in the environment. This review summarizes various
      neurotoxic studies conducted in both cell culture and animals models following
      dieldrin exposure and discusses their relevance to key pathological mechanisms
      associated with nigral dopaminergic degeneration including oxidative stress,
      mitochondrial dysfunction, protein aggregation, and apoptosis.

PMID- 16112330
TI  - Selective alterations of transcription factors in MPP+-induced neurotoxicity in
      PC12 cells.
AB  - MPP(+) (1-methyl-4-phenylpyridinium; the active metabolite of the neurotoxin MPTP
      (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine)) depletes dopamine (DA) content
      and elicits cell death in PC12 cells. However, the mechanism of MPP(+)-induced
      neurotoxicity is still unclear. In this study, the dose response and time-course
      of MPP(+)-induced DA depletion and decreased cell viability were determined in
      nerve growth factor (NGF)-differentiated PC12 cells. The alteration of
      transcription factors (TFs) induced by MPP(+) from a selected dose level and time
      point was then evaluated using protein/DNA-binding arrays. K-means clustering
      analysis identified four patterns of protein/DNA-binding changes. Three of the 28
      TFs identified in PC12 cells increased by 100% (p53, PRE, Smad SBE) and 2
      decreased by 50% (HSE, RXR(DR1)) of control with MPP(+) treatment. In addition,
      three TFs decreased within the range of 33-50% (TFIID, E2F1, CREB) and two TFs
      increased within the range of 50-100% (PAX-5, Stat4). An electrophoretic mobility
      shift assay (EMSA) was used to confirm the changes of p53 and HSE. The observed
      changes in TFs correlated with the alterations of DA and cell viability. The data
      indicates that selective transcription factors are involved in MPP(+)-induced
      neurotoxicity and it provides mechanistic information that may be applicable to
      animal studies with MPTP and clinical studies of Parkinson's disease.

PMID- 16112329
TI  - Perinatal heptachlor exposure increases expression of presynaptic dopaminergic
      markers in mouse striatum.
AB  - Although banned in the 1970s, significant levels of the organochlorine pesticide
      heptachlor are still present in the environment raising concern over potential
      human exposure. In particular, organochlorine pesticides have been linked to an
      increased risk of Parkinson's disease. Studies from our laboratory and others
      have demonstrated that exposure of laboratory animals to heptachlor alters the
      levels and function of the dopamine transporter (DAT), an integral component of
      dopaminergic neurotransmission and a gateway for the dopaminergic neurotoxin
      MPTP. In this study, we examined the effects of developmental exposure to
      heptachlor on DAT, and other key components of the dopaminergic system, including
      the vesicular monoamine transporter 2 (VMAT2), tyrosine hydroxylase (TH), and
      aromatic amino acid decarboxylase (AADC). Female C57BL/6J mice received 0 or
      3mg/kg heptachlor in peanut butter every 3 days for 2 weeks prior to breeding and
      throughout gestation and lactation until the offspring were weaned on postnatal
      day (PND) 21. On postnatal day 28, DAT, VMAT2, and TH levels were increased by
      100, 70, and 30%, respectively, with no change in AADC levels or total dopamine
      levels. The ratio of DAT:VMAT2 was increased 29%. Since an increase in the
      DAT:VMAT2 ratio appears to predict susceptibility of brain regions to Parkinson's
      disease (PD) and results in increased toxicity of MPTP, these results suggest
      that alterations of the dopaminergic system by developmental heptachlor exposure
      may increase the susceptibility of dopamine neurons to toxic insult.

PMID- 16112331
TI  - Chemical warfare agents--still taboo poisons?

PMID- 16112332
TI  - The excitatory amino acid transporters: pharmacological insights on substrate and
      inhibitor specificity of the EAAT subtypes.
AB  - L-glutamate serves as the primary excitatory neurotransmitter in the mammalian
      CNS, where it can contribute to either neuronal communication or
      neuropathological damage through the activation of a wide variety of excitatory
      amino acid (EAA) receptors. By regulating the levels of extracellular L-glutamate
      that have access to these receptors, glutamate uptake systems hold the potential
      to effect both normal synaptic signaling and the abnormal over-activation of the
      receptors that can trigger excitotoxic pathology. Among the various membrane
      transporters that are capable of translocating this dicarboxylic amino acid, the
      majority of glutamate transport in the CNS, particularly as related to excitatory
      transmission, is mediated by the high-affinity, sodium-dependent, excitatory
      amino acid transporters (EAATs). At least 5 subtypes of EAATs have been
      identified, each of which exhibits a distinct distribution and pharmacology. Our
      growing appreciation for the functional significance of the EAATs is closely
      linked to our understanding of their pharmacology and the consequent development
      of inhibitors and substrates with which to delineate their activity. As was the
      case with EAA receptors, conformationally constrained glutamate mimics have been
      especially valuable in this effort. The success of these compounds is based upon
      the concept that restricting the spatial positions that can be occupied by
      required functional groups can serve to enhance both the potency and selectivity
      of the analogues. In the instance of the transporters, useful pharmacological
      probes have emerged through the introduction of additional functional groups
      (e.g., methyl, hydroxyl, benzyloxy) onto the acyclic backbone of glutamate and
      aspartate, as well as through the exploitation of novel ring systems (e.g.,
      pyrrolidine-, cyclopropyl-, azole-, oxazole-, and oxazoline-based analogues) to
      conformationally lock the position of the amino and carboxyl groups. The focus of
      the present review is on the pharmacology of the EAATs and, in particular, the
      potential to identify those chemical properties that differentiate the processes
      of binding and translocation (i.e., substrates from non-substrate inhibitors), as
      well as strategies to develop glutamate analogues that act selectively among the
      various EAAT subtypes.

PMID- 16112334
TI  - Tooth morphology and characteristics of non-carious cervical lesions.
AB  - OBJECTIVES: Two 3-dimensional models, one of a lower second premolar and one of a
      lower central incisor were used to investigate effects of load on the location
      and magnitude of cervical strains. METHODS: Point loads of 100 N were applied to
      the model premolar (at the cusp tip, parallel and 45 degrees to the long axis of
      the tooth) and incisor (at the mid-buccal point on incisal edge, parallel and 45
      degrees to the long axis of the tooth). Outputs were presented in the form of
      tensile-strain contours and vector plots. RESULTS: Strains were concentrated near
      the cementoenamel junction (CEJ) regardless of load direction, and oblique
      loading showed higher tensile strains, opposite to the point of loading, than
      vertical loading for both models. For the premolar model, regardless of loading
      direction, strains were concentrated at the mid- buccal CEJ. In contrast, under
      vertical loading on the incisor model, tensile strains were concentrated at the
      line-angle of CEJ. From oblique loads, vector plots of both models showed tensile
      vectors in vertical directions while vertical loads showed tensile vectors in
      horizontal directions. CONCLUSION: Mechanisms of non-carious cervical lesions
      (NCCLs) may in part be due the changing orientation of tensile strains as well as
      their magnitude. Stress concentration at the CEJ related well to the common
      location of clinical NCCLs. The crown-root morphology may have an influence on
      the initial location of non-carious cervical lesions.

PMID- 16112333
TI  - The relationship between enamel softening and erosion caused by soft drinks at a
      range of temperatures.
AB  - OBJECTIVES: Investigations of the erosive potential of soft drinks are usually
      performed at room or body temperature, but drinks are more frequently served
      chilled, with ice, or hot. Since the rate of chemical reactions usually increases
      with temperature, it is predicted that erosion is more severe at high
      temperatures and reduced at low temperatures. The aim of this study was to
      investigate the correlation between enamel softening, enamel erosion, and
      temperature. METHODS: Atomic force microscopy nanoindentation and non-contact
      optical profilometry were used to assess changes in enamel nanomechanical
      properties after 5 min and erosive material loss after 30 min exposure to two
      different non-carbonated soft drinks at 4, 25, 50 and 75 degrees C. RESULTS: For
      one drink (Robinson's Original Juice Drink), there was a statistically
      significant difference between nanomechanical properties and erosion depth at all
      temperatures, with softening and erosion increasing with temperature. For another
      drink (Ribena ToothKind Juice Drink), there was a slight softening and virtually
      no material loss, and temperature had no statistically significant impact on
      erosion. There was a good linear correlation (R2 = 0.94) between nanomechanical
      properties and material loss. CONCLUSIONS: The difference between the drinks can
      be explained by their composition. For the erosive drink, material loss
      increased, and nanohardness decreased, approximately linearly with temperature.
      The correlation between softening and erosion demonstrated that nanomechanical
      properties after very short erosion times can be considered a good predictor of
      bulk material loss after considerably longer erosion times.

PMID- 16112335
TI  - Evaluation of a reinforced slot design for CEREC system to restore extensively
      compromised premolars.
AB  - OBJECTIVES: The structural stability and adhesive strength of a large-cavity
      premolar with a CEREC restoration is a frequent problem in long-term use. This
      study sought to determine whether an additional reinforced slot could increase
      tooth/ceramic retention using finite element (FE) analysis and fracture testing.
      METHODS: The cavity was designed in a typical MODL restoration failure shape when
      the lingual cusp has been lost. Two FE restored-tooth models with different
      cavity designs were created using image processing, contour stacking, and mesh
      generation. Interfacial (normal and shear) stresses were then calculated with and
      without the slot design for restored teeth under lateral and axial forces and
      different interfacial conditions (bonded and de-bonding). For validation, a
      fracture experiment was performed with and without reinforced slot designs for
      large ceramic CEREC restorations. RESULTS: The maximum stresses at the buccal
      wall increased when a lateral occlusal force acted on the restored tooth with a
      slot design. Conversely, the interfacial stresses decreased when the restored
      tooth received a uniform axial occlusal force. After de-bonding on the buccal
      tooth/ceramic interface, the stresses increased by an average factor of three
      over those obtained with a bonded interface. The fracture forces were consistent
      with the tendencies predicted in FE analyses. CONCLUSIONS: An additional
      reinforced slot for the CEREC restoration of a large cavity could increase
      retention when a restored tooth receives an axial occlusal load. However, the
      benefits of a slot seem to be doubtful for a premolar often subjected to a
      lateral load.

PMID- 16112336
TI  - Effect of CPP-ACP paste on mechanical properties of bovine enamel as determined
      by an ultrasonic device.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of Casein
      Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) paste on demineralization of
      bovine enamel by measuring changes in the ultrasound transmission velocity.
      METHODS: The enamel specimens were prepared by cutting bovine teeth into blocks.
      The specimens were stored in 0.1 M lactic acid buffer solution (pH 4.75, Ca 0.75
      mM, P 0.45 mM) for 10 min twice a day, and then stored in the artificial saliva
      (pH 7.0). Other specimens were stored in a 10-times diluted solution of CPP-ACP
      paste and a placebo paste without CPP-ACP for 10 min, followed by 10 min
      immersion into a demineralization solution twice a day before storage in the
      artificial saliva. The propagation time of longitudinal ultrasonic waves was
      measured by a Pulser-Receiver (Model 5900, Panametrics) with a transducer (V112,
      Panametrics). Six specimens were used for each condition, and one-way ANOVAs
      followed by the Tukey HSD tests (alpha = 0.05) were done. RESULTS: The sonic
      velocity was found to decrease with time for specimens stored in the
      demineralization solution. On the other hand, a significant increase in sonic
      velocity was found for specimens stored in the CPP-ACP solution. CONCLUSIONS:
      From the result of this study, it was suggested that the conditions of de- and
      remineralization of the enamel structure could be measured non-destructively by
      using an ultrasonic pulse method. It could be concluded that the inorganic
      components contained in high concentrations in CPP-ACP acted to enhance
      remineralization of the enamel structure.

PMID- 16112337
TI  - Marginal toughness of bonded dental ceramics evaluated by determination of the
      crack length.
AB  - OBJECTIVES: The objective of this study was to evaluate the toughness of dental
      ceramics near a bonded interface using indentation microfracture. METHODS: The
      ceramics used in the present study were two leucite-reinforced ceramics (IPS
      Empress and Finesse), one lithia-based ceramic (IPS Empress 2) and one mica-based
      ceramic (OCC). The ceramic discs were processed according to the manufacturers
      instructions and were bonded to resinous discs using a resin composite cement.
      The bonded specimens were sectioned perpendicularly, and micro-Vickers
      indentations were imprinted at several distances from the bonded interface in the
      polished ceramic sections. The lengths between the two ends of the radial cracks
      along the bonded interface were measured. RESULTS: Crack lengthening was
      recognized when the distance was within 70 microm. In each ceramic, the
      indentation crack length at 40 microm from the interface was significantly longer
      than the length at the inner point of the ceramic material (p<0.05). The order of
      the mean indentation crack lengths at 40 microm was OCC>Finesse>IPS Empress 2>IPS
      Empress, while the order at 490 microm was Finesse>OCC>IPS Empress>IPS Empress 2.
      There was a difference between the orders at 40 microm and at 490 microm.
      SIGNIFICANCE: The behaviour of the indentation crack near the interface differs
      from that which is distant from the interface. Therefore, it is impossible to
      estimate the marginal toughness of the ceramic based on the indentation
      microfracture at the inner point of the ceramic.

PMID- 16112338
TI  - Removal of basic dye (Astrazon Blue FGRL) using macroalga Caulerpa lentillifera.
AB  - The macroalga Caulerpa lentillifera was found to have adsorption capacity for a
      basic dye, Astrazon Blue FGRL. For the whole range of concentrations employed in
      this work (20-1280 mgl(-1)), the adsorption reached equilibrium within the first
      hour. The kinetic data corresponded well with the pseudo second-order kinetic
      model where the rate constants decreased as initial dye concentrations increased.
      At low dye concentrations (20-80 mgl(-1)), an increase in the adsorbent dosage
      resulted in a higher removal percentage of the dye, but a lower amount of dye
      adsorbed per unit mass (q). The adsorption isotherm followed both the Langmuir
      and Freundlich models within the temperature range employed in this work (18-70
      degrees C). The highest maximum adsorption capacity (q(m)) was obtained at 50
      degrees C. The enthalpy of adsorption was estimated at 14.87 kJmol(-1) suggesting
      a chemical adsorption mechanism.

PMID- 16112339
TI  - Why most conservation monitoring is, but need not be, a waste of time.
AB  - Ecological conservation monitoring programmes abound at various organisational
      and spatial levels from species to ecosystem. Many of them suffer, however, from
      the lack of details of goal and hypothesis formulation, survey design, data
      quality and statistical power at the start. As a result, most programmes are
      likely to fail to reach the necessary standard of being capable of rejecting a
      false null hypothesis with reasonable power. Results from inadequate monitoring
      are misleading for their information quality and are dangerous because they
      create the illusion that something useful has been done. We propose that
      conservation agencies and those funding monitoring work should require the
      demonstration of adequate power at the outset of any new monitoring scheme.

PMID- 16112340
TI  - Designing reverse-flow packed bed reactors for stable treatment of volatile
      organic compounds.
AB  - Reverse-flow packed bed reactors can be used to treat gaseous pollutants from
      chemical plants. This article describes the design and operation of a modified
      reverse-flow reactor (MRFR) which has a recuperator on each end of the reactor
      and a reaction zone in the middle. The recuperators have low thermal dispersion
      and the reaction zone has a high thermal dispersion, obtained by placing metal
      inserts into the bed, parallel with the gas flow. Performance of the MRFR during
      extended lean and rich conditions is determined with analytical analysis and
      compares well with numerical simulations of CO oxidation; however, the theory is
      expected to be useful for any reaction kinetics. A major advantage of this MRFR
      design is an extended time for the reactor to extinguish during lean conditions.
      This work also describes MRFR performance with internal reactor cooling, which
      can be used as a control mechanism to maintain reactor temperature for proper
      removal of volatile organic compounds.

PMID- 16112341
TI  - Optimal estuarine sediment monitoring network design with simulated annealing.
AB  - An objective function based on geostatistical variance reduction, constrained to
      the reproduction of the probability distribution functions of selected physical
      and chemical sediment variables, is applied to the selection of the best set of
      compliance monitoring stations in the Sado river estuary in Portugal. These
      stations were to be selected from a large set of sampling stations from a prior
      field campaign. Simulated annealing was chosen to solve the optimisation function
      model. Both the combinatorial problem structure and the resulting candidate
      sediment monitoring networks are discussed, and the optimal dimension and spatial
      distribution are proposed. An optimal network of sixty stations was obtained from
      an original 153-station sampling campaign.

PMID- 16112342
TI  - Metals in vineyard soils of the Penedes area (NE Spain) after compost
      application.
AB  - The application of organic wastes to improve soil physical characteristics in
      mechanized vineyards planted after land levelling is becoming a common practice
      in Mediterranean areas. It may be useful as an additional source of organic
      matter and nutrients, but these wastes could also have negative effects due to
      their metal content. The aim of the study was to evaluate the influence of
      compost application on soil metal contents in mechanized vineyard soils of the
      Spanish Mediterranean area, where this practice is repeated every three years.
      The study was carried out in a ten-year-old vineyard where the main soil type is
      Typic Calcixerept. Composted cattle manure was applied in alternate rows, at a
      rate of 40 Mgha(-1) dry-weight. Nine sampling points were located along the
      slopes of two plots: a levelled plot prepared for mechanization with large soil
      disturbance movements within the plot, and a plot of undisturbed soil. At each
      location, soil samples were taken in both treated and untreated soils. Total
      concentrations (digestion with aqua regia) and the extractable DTPA (Diethylene
      triaminepentacetic)-CaCl2-TEA (Triethanolamine) fractions of Cu, Zn and Mn were
      analyzed in each sample. For Cu and Zn, the initial concentration was higher in
      the undisturbed plot. In both cases, total Cu and total Zn were positively
      affected by manure input and the concentration in treated soils was significantly
      higher than in untreated soil. For Mn, the initial concentration was higher in
      disturbed soils than in undisturbed ones, and although in both scenarios the
      concentrations increased with manure, no significant differences were found
      between treated and untreated soils. The extractable fraction also increased in
      treated versus untreated soils, although for Cu and Mn the extractable/total
      metal ratio was similar in treated and untreated soils. After one compost
      application, total metal contents increased significantly, particularly for Zn.
      Most of those metals are accumulated in the soil, due to the soil
      characteristics.

PMID- 16112343
TI  - Angioedema.
AB  - Although first described more than 130 years ago, the pathophysiology, origin,
      and management of the several types of angioedema are poorly understood by most
      dermatologists. Although clinically similar, angioedema can be caused by either
      mast cell degranulation or activation of kinin formation. In the former category,
      allergic and nonsteroidal anti-inflammatory drug-induced angioedema are
      frequently accompanied by urticaria. Idiopathic chronic angioedema is also
      usually accompanied by urticaria, but can occur without hives. In either case, an
      autoimmune process leading to dermal mast cell degranulation occurs in some
      patients. In these patients, histamine-releasing IgG anti-FcepsilonR1
      autoantibodies are believed to be the cause of the disease, removal or
      suppression by immunomodulation being followed by remission. Angiotensin
      converting enzyme inhibitor-induced angioedema is unaccompanied by hives, and is
      caused by the inhibition of enzymatic degradation of tissue bradykinin.
      Hereditary angioedema, caused by unchecked tissue bradykinin formation, is
      recognized biochemically by a low plasma C'4 and low quantitative or functional
      C'1 inhibitor. Progress has now been made in understanding the molecular genetic
      basis of the two isoforms of this dominantly inherited disease. Recently, a third
      type of hereditary angioedema has been defined by several groups. Occurring
      exclusively in women, it is not associated with detectable abnormalities of the
      complement system. Angioedema caused by a C'1 esterase inhibitor deficiency can
      also be acquired in several clinical settings, including lymphoma and autoimmune
      connective tissue disease. It can also occur as a consequence of specific anti
      C'1 esterase autoantibodies in some patients. We have reviewed the clinical
      features, diagnosis, and management of these different subtypes of angioedema.
      LEARNING OBJECTIVE: After completing this learning activity, participants should
      be aware of the classification, causes, and differential diagnosis of angioedema,
      the molecular basis of hereditary and non-hereditary forms of angioedema, and be
      able to formulate a pathophysiology-based treatment strategy for each of the
      subtypes of angioedema.

PMID- 16112344
TI  - Breslow depth of cutaneous melanoma: impact of factors related to surveillance of
      the skin, including prior skin biopsies and family history of melanoma.
AB  - BACKGROUND: Because the early detection of cutaneous melanoma can dramatically
      improve survival, identification and surveillance of persons at risk have
      received much attention. OBJECTIVE: Our purpose was to examine the influences of
      personal or family history, patterns of detection, and prior skin biopsies
      (considered to be a measurement of surveillance by medical personnel) on the
      Breslow depth of cutaneous melanomas. METHODS: A retrospective cohort analysis of
      218 patients with a history of at least one invasive cutaneous melanoma who
      visited the Yale Pigmented Lesion Clinic between January 1995 and January 1996
      was performed. Data on patterns of detection, melanocytic nevi, and skin biopsies
      before and after the initial diagnosis of melanoma were collected, and patients
      with a family history of melanoma were compared with sporadic patients. RESULTS:
      Initial melanomas discovered by dermatologists were more likely to be 0.75 mm or
      less in depth than those found by other physicians (P = .03). Although patients
      detected 45% of the initial primary melanomas (98/218), dermatologists discovered
      80% of the second primary tumors (33/41; P = .001). A personal history of
      melanoma was predictive of a thinner Breslow depth (P = .01), but a family
      history of melanoma was not. Having a biopsy of any type or combination of types
      of skin lesion(s) performed in the 5 years, 2 years, or 1 year before the first
      diagnosis of melanoma did not predict a melanoma of thinner Breslow depth among
      either familial or sporadic patients. The mean number of skin biopsies performed
      per patient was 8 times higher in the 5-year period after (5.6) versus the 5-year
      period before (0.7) the initial diagnosis of melanoma, with a peak in the first
      year after the diagnosis (2.3 vs 0.25 in the prior year). In 27 patients, one or
      more skin biopsies were performed in the year before the initial diagnosis of
      melanoma; 41% of these biopsies (23/56) were of lesions in normally exposed sites
      (eg, the face, neck, and forearms) compared with 22% of the melanomas (6/27).
      LIMITATIONS: Since an invasive melanoma (with the possible exception of a nodular
      melanoma) would likely have been present for at least a year, plausible
      explanations for why evidence of previous dermatologic care did not appear to
      result in earlier detection include performance of a limited rather than a total
      body skin examination as well as subtle clinical features of early melanomas.
      However, this study cannot give weight to these explanations because at the time
      new Pigmented Lesion Clinic patients were not routinely asked about previous
      total body skin examinations. CONCLUSIONS: The disappointing trends seen in this
      study, with neither the well-established risk factor of a family history of
      melanoma nor previously having a skin biopsy predicting thinner melanomas,
      highlight the need to establish criteria defining the subset of patients for whom
      appropriate management requires periodic total body skin examination.

PMID- 16112345
TI  - Botulinum toxin type A injections: adverse events reported to the US Food and
      Drug Administration in therapeutic and cosmetic cases.
AB  - BACKGROUND: Botulinum toxin type A (BTA) (Botox) received Food and Drug
      Administration (FDA) approval for therapeutic treatment of strabismus and
      blepharospasm in 1989, cervical dystonia in 2000, and cosmetic treatment of
      glabellar wrinkles (Botox Cosmetic) in 2002. In 2002 alone there were
      approximately 1.1 to 1.6 million patients using cosmetic BTA. Our objective was
      to review adverse event (AE) reporting to the FDA after BTA administration.
      METHODS: We reviewed all (therapeutic and cosmetic use) serious (per FDA
      regulations) AEs reported to the FDA for the 13.5 years since licensure of the
      product (December 1989-May 2003) and nonserious AEs reported from December 2001
      to November 2002. AEs are reported to the FDA through the MedWatch system.
      RESULTS: We reviewed 1437 AE reports; 406 followed therapeutic use of BTA (217
      serious and 189 nonserious) and 1031 followed cosmetic use (36 serious and 995
      nonserious). Reported AEs occurred predominantly in female patients, with a
      median age of 50 years. In the year December 2001 to November 2002, when both
      serious and nonserious reports were evaluated, the proportion of reports
      classified as serious was 33-fold higher for therapeutic than for cosmetic cases.
      The 217 serious AEs reported in therapeutic cases involved a wide spectrum of
      events and included all 28 reported deaths. Among cosmetic users, no deaths were
      reported and, of the 36 serious AEs, 30 were included as possible complications
      in the FDA-approved label. The remaining 6 serious AEs did not display a pattern
      suggesting a common causal relationship to BTA. Among the 995 cosmetic cases
      reported to have nonserious AEs, most commonly noted were lack of effect (623,
      63%), injection site reaction (190, 19%), and ptosis (111, 11%). CONCLUSIONS:
      Serious AEs were more likely to be reported for therapeutic than for cosmetic
      use, which may be related to higher doses, complicated underlying diseases, or
      both. Among cosmetic cases, few serious AEs were reported, and these were
      predominantly events that were previously recognized in clinical trials of BTA
      for the labeled use. This study is limited primarily by the incomplete nature of
      AE reporting by clinicians. Numerous departures from FDA-approved recommendations
      for drug dose, dilution, handling, site of injection, and storage were noted in
      these AE reports.

PMID- 16112346
TI  - Patch test results from the Mayo Clinic Contact Dermatitis Group, 1998-2000.
AB  - BACKGROUND: Patch testing is a diagnostic tool for the evaluation of patients
      with suspected allergic contact dermatitis. A standard series of allergens
      similar to that used by the North American Contact Dermatitis Group (NACDG) is
      used at Mayo Clinic. OBJECTIVE: Our aim was to report the results of patch
      testing with a standard series at Mayo Clinic from July 1, 1998, to Dec 31, 2000
      and to compare our findings with those of the NACDG during the same period.
      METHODS: The results of patch testing with the standard series at Mayo Clinic
      were examined. Positive reaction rates were compared between Mayo Clinic and the
      NACDG. RESULTS: During the 30-month period, 1324 Mayo Clinic patients were patch
      tested with a standard series of allergens (mean, 60 allergens), whereas the
      NACDG standard series during this period included 50 allergens. Overall, 917
      patients (69.3%) had at least one positive reaction and 606 patients (45.8%) had
      two or more positive reactions. The 10 allergens used both by Mayo Clinic and by
      the NACDG that most frequently caused positive reactions were nickel sulfate
      hexahydrate, balsam of Peru (Myroxylon pereirae), neomycin sulfate, cobalt
      chloride, fragrance mix, potassium dichromate (0.25%), thimerosal, bacitracin,
      formaldehyde, and glutaraldehyde. Statistically significant differences in
      positive reaction rates (P < .05) were observed for 12 of the 43 allergens common
      to both Mayo Clinic and the NACDG. CONCLUSION: With large standard patch test
      series, one can identify commonly encountered and potentially relevant contact
      allergens.

PMID- 16112347
TI  - The role of cytotoxic skin-homing CD8+ lymphocytes in cutaneous cytotoxic T-cell
      lymphoma and pityriasis lichenoides.
AB  - BACKGROUND: Pityriasis lichenoides (PL) is a rare cutaneous lymphoproliferative
      disorder of unknown origin. Malignant transitions of PL have been described, but
      are very rare. We recently observed the fatal course of a 26-year-old patient who
      presented with a clinical picture resembling PL but had cytotoxic CD8+ T-cell
      lymphoma of the skin (CxCTL). This case prompted us to reinvestigate the role of
      cytotoxic T lymphocytes in PL and its relationship to antiviral immunity.
      METHODS: Skin biopsy specimens of 11 patients with PL and two biopsy specimens of
      CxCTL were included. In all, 5 biopsy specimens taken from healthy skin and 5
      samples of varicella-zoster virus (VZV) skin lesions were analyzed for control
      purposes. The inflammatory infiltrate was characterized by immunohistochemistry
      using monoclonal antibodies against CD3, CD4, CD8, CD20, cutaneous lymphocyte
      associated antigen (CLA), CCR4, CXCR3, Granzyme B, Tia-1, and MxA. Flow cytometry
      was used to analyze the expression of chemokine receptors on peripheral blood
      mononuclear cells in CxCTL. RESULTS: The CxCTL skin lesions were dominated by a
      dense infiltration of CD8+ cytotoxic lymphocytes with a skin-homing CLA+ CCR4+
      phenotype. PL and VZV skin lesions were also characterized by a predominantly
      CD8+ T cellular infiltrate with strong expression of the cytotoxic molecules
      Granzyme B and Tia-1 and the skin-homing molecules CLA and CCR4. Coexpression
      analyses confirmed that skin CLA+ CD8+ cytotoxic T cells are present in CxCTL,
      VZV, and PL skin lesions. Strong lesional production of the antiviral protein
      MxA, which is specifically induced by type I interferons, could be found in all
      investigated disorders. The study was based on histologic, immunohistologic, and
      flow cytometric analyses in a limited number of patients, because of the rareness
      of the investigated diseases. CONCLUSION: Our results revealed a striking
      similarity between the immunohistologic picture of malignant CxCTL, benign PL,
      and VZV skin lesions. Strong expression of the antiviral protein MxA in all
      disorders supports the view that a common antiviral immune response pattern leads
      to aberrant skin recruitment of CLA+ CCR4+ cytotoxic T lymphocytes in PL and
      CxCTL.

PMID- 16112348
TI  - Association of change in clinical status and change in the percentage of the
      CD4+CD26- lymphocyte population in patients with Sezary syndrome.
AB  - BACKGROUND: Because there are currently many effective therapies available for
      Sezary syndrome, close monitoring of disease progression is required in order for
      a clinician to know when to institute or change an intervention. It has been our
      clinical experience that changes in patients' CD4+CD26- T-cell populations of
      peripheral blood lymphocytes herald changes in their clinical status. OBJECTIVE:
      Our purpose was to evaluate whether a change in patients' CD4+CD26- population of
      T cells presages a change in their clinical status. We also sought to investigate
      the association between a change in T-cell populations that are CD4+CD7-, CD8+,
      CD56+, and the CD4+/CD8+ T-cell ratio and a change in the patient's clinical
      status. METHODS: We conducted a retrospective chart review analysis of 21
      patients with Sezary syndrome who had flow cytometry, usually including levels of
      CD4+CD26-, CD4+CD7-, CD8+, CD56+, and CD4+/CD8+ ratios measured at two time
      periods, 12 weeks apart. RESULTS: We report two cases in which changes in
      patients' clinical status were preceded by several weeks by a change in their
      CD4+CD26- level. We report weak associations between a decreasing CD4+CD26- T
      cell population, a decreasing CD4+CD7- population, an increasing CD56+
      population, and an improving clinical status. We also report stronger
      associations between both a decreasing CD8+ population and an increasing
      CD4+/CD8+ ratio and a worsening clinical status. LIMITATIONS: The study was
      limited by the number of patients and the time period over which the study was
      conducted. In addition, varying configurations of CD4+CD26- T-cell populations
      were observed that may have limited the utility of this measurement. CONCLUSIONS:
      Flow cytometry assays of patients' blood and, in particular, measurement of the
      CD4+CD26- population of lymphocytes over time may be a valuable tool for
      monitoring patients with Sezary syndrome. There exist varying configurations of
      CD26 T lymphocytes that may cause differences in standards for what is considered
      positive and negative between observers. Further prospective analysis involving
      larger groups of patients is recommended.

PMID- 16112349
TI  - Epidemiological and clinical characteristics of classic Kaposi's sarcoma in Peru.
AB  - BACKGROUND: Classic Kaposi sarcoma (KS) occurs predominantly among the elderly,
      with predominance among Jews, Italians, and Greeks. Classic KS has been seen
      relatively frequently in Peru. OBJECTIVE: Our purpose was to outline the
      epidemiological and clinical profile of classic KS in Peru. METHODS:
      Epidemiological and clinical features of all classic KS cases diagnosed between
      1969 and 2003 at Hospital Nacional Cayetano Heredia (HNCH) and between 1946 and
      2004 at Instituto Nacional de Enfermedades Neoplasicas (INEN) were reviewed and
      studied retrospectively. RESULTS: An overall incidence of 2.54 per 10,000
      attended patients was obtained at the INEN during the 48-year period (mean, 2.39;
      standard deviation: 1.99; 95% confidence interval, 2.92-1.86). Twenty-one cases
      were discovered at HNCH and 106 cases at INEN. A male/female ratio of 2.62:1 was
      found. Mean age at diagnosis was 68.5 years. Lower limbs were involved in 109
      patients (85.8%); the trunk was involved in 11 patients (8.6%). Nodules were the
      most common type of lesion (85.8%); less commonly found were plaques (27.5%),
      macules (12.5%), papules (12.5%), and ulcers (8.6%). Sixty-two patients had no
      symptoms (48.8%). Pain was the most common symptom (26.7%), followed by edema
      (21.2%), bleeding (14.9%), and pruritus (3.9%). A second primary malignancy was
      found in 11 patients (8.6%). LIMITATIONS: These results were obtained from
      patients with classic KS in Peru and may not be applicable to other populations.
      CONCLUSION: Classic KS is quite common in Peru with sporadic cases found
      throughout the country and some clustering in the coastal region. Classic KS in
      Peru has a clinical presentation that is very similar, but not identical, to the
      classic KS described in the Mediterranean region, exhibiting some special
      clinical and epidemiological characteristics with a nodular, nonsymmetric
      presentation that usually affects the lower extremities.

PMID- 16112350
TI  - Lymphangioma circumscriptum: treatment with hypertonic saline sclerotherapy.
AB  - A 38-year-old woman came for treatment of multiple clear vesicles and hemorrhagic
      papules on the posterior aspect of the right shoulder and the right axillary
      vault of 5 years' duration. These lesions would spontaneously manifest as clear
      or blood-filled vesicles (or both) and appear to be exacerbated by physical
      contact from certain articles of clothing. A biopsy was done and the results
      revealed lymphangioma circumscriptum. The purpose of this case study was to
      evaluate a new form of treatment of lymphangioma circumscriptum with the use of
      23.4% hypertonic saline sclerotherapy. The patient's lymphangioma circumscriptum
      significantly resolved with minimal side effects, such as mild hyperpigmentation.
      Decreased sensitivity was noted and no further treatment was indicated. This case
      showed that hypertonic saline 23.4% solution can be effective in treating the
      appearance of vesicles containing clear fluid or lymph and those containing red
      blood cells in superficial lymphangiomas and that this treatment can be
      considered for long-term management of lymphangioma circumscriptum.

PMID- 16112351
TI  - Basal cell carcinoma treated with Mohs surgery in Australia I. Experience over 10
      years.
AB  - BACKGROUND: Only a few prospective studies have been published on surgical
      treatments for cutaneous basal cell carcinoma (BCC). OBJECTIVE: Our purpose was
      to report the clinical findings of all patients with BCC treated with Mohs
      micrographic surgery (MMS) in Australia between 1993 and 2002. METHOD: This
      prospective, multicenter case series included all patients in Australia treated
      with MMS for BCC, who were monitored by the Skin and Cancer Foundation between
      1993 and 2002. The main outcome measures were patient demographics, reason for
      referral, duration of tumor, site, preoperative tumor size, recurrences before
      MMS, histologic classification of malignancy, and postoperative defect size.
      RESULTS: The study included 11,127 patients (47% females and 53% males) with a
      mean age of 62 years (range, 15-98 years). In 43.8% of cases BCC was a recurrent
      tumor. Most of the tumors (98.3%) were on the head and neck area, most commonly
      on the nose (39%), cheek and maxilla (16.5%), periocular area (12.7%), and
      auricular region (11.4%). The most common histologic subtypes were infiltrating
      (30.7%), nodulocystic (24.2%), and superficial (13.6%). Previously recurrent
      tumors were larger than primary tumors (P < .001), had a larger postexcision
      defect and more subclinical extension, and required more levels of excision (P <
      .001). LIMITATIONS: Data were missing for some outcome measures. CONCLUSION: This
      large prospective series of BCC managed by MMS is characterized by a high
      percentage of high-risk tumors. Most tumors were located in the mid-facial area
      and the histologic subtype was mainly infiltrating or nodulocystic. That
      previously recurrent tumors were larger and demonstrated a more extensive
      subclinical extension compared with primary tumors emphasizes the importance of
      initial tumor eradication with margin control.

PMID- 16112352
TI  - Basal cell carcinoma treated with Mohs surgery in Australia II. Outcome at 5-year
      follow-up.
AB  - BACKGROUND: Long-term follow-up is essential to evaluate the role of Mohs
      micrographic surgery (MMS) in the treatment for cutaneous basal cell carcinoma
      (BCC). OBJECTIVE: Our purpose was to report the 5-year follow-up outcome of
      patients treated with MMS for BCC. METHOD: This prospective, multicenter case
      series included all patients in Australia treated with MMS for BCC, who were
      monitored by the Skin and Cancer Foundation between 1993 and 2002. Parameters
      recorded were patient demographics, duration of tumor, site, preoperative tumor
      size, recurrences before MMS, histologic classification of malignancy,
      postoperative defect size, and 5-year recurrence after MMS. RESULTS: Three
      thousand three hundred seventy (3370) patients (1594 female and 1776 male
      patients) completed a 5-year follow-up period. Fifty-six percent of the tumors
      were primary and 44% were previously recurrent. Most of them (98.4%) were located
      on the head and neck, and the most common histologic subtypes were nodulocystic
      (29.3%) and infiltrating (28.3%). Recurrence at 5 years was diagnosed in 1.4% of
      primary and in 4% of recurrent tumors. Previous tumor recurrence (P < .001),
      longer tumor duration before MMS (P = .015), infiltrating histology (P = .13),
      and more levels for tumor (P < .001) were the main predictors for tumor
      recurrence after MMS. LIMITATION: Data were missing for some outcome measures.
      CONCLUSION: The low 5-year recurrence rate of BCC with MMS emphasizes the
      importance of margin-controlled excision.

PMID- 16112353
TI  - Basal cell carcinoma treated with Mohs surgery in Australia III. Perineural
      invasion.
AB  - BACKGROUND: Perineural invasion (PNI) is an important factor may possibly
      influence the aggressiveness of basal cell carcinoma (BCC). OBJECTIVE: Our
      purpose was to evaluate the incidence, features, and outcomes of BCC with PNI in
      patients treated with Mohs micrographic surgery (MMS). METHOD: This prospective,
      multicenter case series included all patients in Australia treated with MMS for
      BCC with PNI, who were monitored by the Skin and Cancer Foundation Australia
      between 1993 and 2002. The parameters recorded were patient demographics, reason
      for referral, duration of tumor, site, preoperative tumor size, recurrence before
      MMS, histologic subtypes, postoperative defect size, and recurrence at 5 years
      after MMS. RESULTS: Two-hundred eighty-three patients were diagnosed with PNI.
      Most cases occurred in male patients (61%; P = .006) and in previously recurrent
      tumors (60.4%; P < .001). The infiltrating, morpheic, and basosquamous subtypes
      were more likely to be associated with PNI (P < .0001). Tumor sizes before
      excision and postoperative defect sizes were significantly larger in cases with
      PNI compared with cases with no PNI (P < .001 for both parameters), as was the
      mean number of Mohs excision levels. Seventy-eight patients completed a 5-year
      follow-up period after MMS, and 6 of them (7.7%) were diagnosed with recurrence.
      LIMITATIONS: Data were missing for some outcome measures. CONCLUSION: PNI is an
      uncommon feature of BCC. When present, PNI is associated with larger, more
      aggressive tumors, and the risk of 5-year recurrence is higher. This emphasizes
      the importance of tumor excision with margin control and long-term patient
      monitoring.

PMID- 16112354
TI  - Efficacy of narrow-margin excision of well-demarcated primary facial basal cell
      carcinomas.
AB  - BACKGROUND: A 4-mm surgical margin of clinically normal skin is the current
      standard for elliptical excision of basal cell carcinomas (BCCs). However, a 4-mm
      surgical margin is often not feasible on the face because of cosmetic and
      functional concerns. As such, facial excisions of BCCs are typically performed
      with the appropriate margin determined by the surgeon based on clinical features
      of the tumor. OBJECTIVE: We designed a study to test the efficacy of narrow
      margin elliptical excisions for the treatment of small, well-demarcated facial
      BCCs. METHODS: A total of 134 primary, small (<1 cm), well-demarcated, facial
      nodular BCCs were excised as an ellipse with 1-, 2-, or 3-mm margins around the
      visible border of the tumor. The margin used was decided by the dermatologic
      surgeon based on cosmetic, anatomic, and functional factors, with the goal of
      clearing the tumor in a single excision. Using the Mohs technique for elliptical
      specimens, frozen sections were prepared and examined microscopically to provide
      complete histologic margin control. RESULTS: In all, 134 facial BCCs were
      included in the study. On average, the tumors measured 0.6 x 0.5 cm. Of these, 27
      (20.1%) had positive margins, requiring additional excision. Excisions with 1-, 2
      , and 3-mm margins were associated with positive margins in 16%, 24%, and 13% of
      tumors, respectively. There was no statistically significant difference in the
      occurrence of positive margins based on tumor size, anatomic location, or the
      measured margin used. CONCLUSION: Narrow margins (1-3 mm) are inadequate for the
      excision of small, well-demarcated, primary nodular BCCs of the face. To avoid
      repetitive operations and the risk of recurrence in anatomically sensitive areas,
      these tumors should be treated with standard wide margins (eg, 4 mm), or have
      Mohs micrographic surgery for histologic margin control.

PMID- 16112355
TI  - Accuracy of serial transverse cross-sections in detecting residual basal cell
      carcinoma at the surgical margins of an elliptical excision specimen.
AB  - BACKGROUND: There has been no published study estimating the proportion of
      positive surgical margins that is missed when serial transverse cross-sectioning
      (bread-loafing) is used to histologically evaluate the surgical margins.
      OBJECTIVE: Our purpose was to estimate the accuracy of serial transverse cross
      sectioning (bread-loafing) at 4-mm intervals in detecting the presence of
      residual tumor at the margins of well-defined facial basal cell carcinomas
      excised as an ellipse with 2-mm surgical margins. METHODS: Forty-two small (<1
      cm), well-defined, primary, nonmorpheaform facial basal cell carcinomas that had
      been excised as an ellipse with 2-mm margins and that had positive surgical
      margins utilizing en-face Mohs sections were included. After longitudinal
      bisection of each ellipse, frozen sections were prepared encompassing the entire
      surgical margin. Transparencies with parallel lines spaced at 4-mm intervals were
      superimposed on the histologic slides with the lines perpendicular to the
      epidermal surface. Areas in which the lines intersected tumor at the surgical
      margin were noted. The percentage of tumors that would be detected by serial
      cross sections was calculated on the basis of the percentage of these parallel
      lines that intersected tumor. RESULTS: The 42 tumors had a total of 50 positive
      surgical margins. Overall, the cross-sectional lines intersected tumor 44% of the
      time (95% confidence interval, 37%-51%). Only 5 (10%) of the residual tumors at
      the surgical margins exceeded 4 mm in their longitudinal dimension. In the 9
      sections containing tumor in the deep margin, tumor intersected the lines 39% of
      the time. CONCLUSION: Bread-loafing at 4-mm intervals of elliptical excision
      specimens from facial basal cell carcinomas excised with 2-mm surgical margins is
      only 44% sensitive in detecting residual tumor at the surgical margins. We
      recommend complete histologic margin control by using en face tissue orientation
      (Mohs technique) to identify residual tumor and reduce the risk of tumor
      recurrence after elliptical excision of facial basal cell carcinomas.

PMID- 16112356
TI  - Metastatic basal cell carcinoma diagnosed by sentinel lymph node biopsy.
AB  - Although commonly used in the treatment of melanoma, sentinel lymph node biopsy
      has not yet been successfully used to detect lymphatic metastasis of basal cell
      carcinoma because of exceedingly low rates of metastasis. We describe the use of
      lymphatic mapping and sentinel lymph node biopsy in a patient after basal cell
      carcinoma was identified within a lymphatic vessel in the primary excisional
      specimen. As a result, the patient was found to have clusters of basal cell
      carcinoma in a sentinel lymph node resected from the right deltopectoral groove.
      Although metastatic basal cell carcinoma is exceedingly rare, we conclude that
      sentinel lymph node biopsy may be useful for certain high-risk lesions, such as
      lesions demonstrating histologic evidence of lymphatic invasion. Further
      experience is necessary to determine the clinical usefulness of sentinel node
      biopsy in these patients and its effect on patient survival.

PMID- 16112357
TI  - Primary cutaneous B-cell lymphoma.
AB  - Primary cutaneous B-cell lymphomas include extranodal marginal zone B-cell
      lymphoma, follicular lymphoma, large B-cell lymphoma, and, rarely, mantle cell
      lymphoma. Our purpose in conducting this review was to determine the clinical and
      behavioral characteristics of primary cutaneous B-cell lymphomas, their
      relationship to infectious triggers, and therapeutic response. We conducted a
      retrospective chart review of 23 adult patients presenting to the dermatology
      clinic at M. D. Anderson Cancer Center with primary cutaneous B-cell lymphoma
      between January 1999 and May 2003. Primary cutaneous B-cell lymphomas generally
      present on the head and neck, with the trunk and extremities afflicted to a
      lesser extent. Patients were found to have serologic evidence of prior infection
      with Borrelia burgdorferi (n = 10), Helicobacter pylori (n = 5), and Epstein-Barr
      virus (n = 6). Overall, treatment of primary cutaneous B-cell lymphoma should
      involve multiple modalities; however, specific treatment aimed at concurrent or
      suspected infection, particularly B burgdorferi, is a helpful adjunct and may
      achieve complete remission in a small subset of patients.

PMID- 16112358
TI  - Skin cancer in African Americans.

PMID- 16112359
TI  - Escharotic and other botanical agents for the treatment of skin cancer: a review.

PMID- 16112360
TI  - Surgical Pearl: Localized pressure from routine surgical instruments provides
      safe and effective temporary hemostasis.

PMID- 16112361
TI  - Surgical Pearl: Surgical tape for dressing of epidermal grafts in lip vitiligo.

PMID- 16112362
TI  - Pterygium inversum unguis associated with stroke.
AB  - Pterygium inversum unguis (PIU) is an uncommon nail abnormality in which the
      distal nail bed adheres to the ventral surface of the nail plate with
      obliteration of the distal nail groove. This rare condition, whether congenital,
      acquired, or idiopathic, has been reported in a few patients. Because of the
      rarity of this condition, the exact origin remains speculative. In addition,
      there have been no histopathologic features described in PIU. We describe an
      unusual case of acquired PIU of the right fingernails alone associated with a
      cerebral vascular accident resulting in right-sided paralysis and sensory
      deficit. We also present the first histologic features of PIU.

PMID- 16112363
TI  - Itch, pain, and burning sensation are common symptoms in mild to moderate chronic
      venous insufficiency with an impact on quality of life.
AB  - To our knowledge there are no studies evaluating the prevalence and
      characteristics of itch, pain, and burning sensation among patients with mild to
      moderate chronic venous insufficiency or assessing the impact of these symptoms
      on quality of life. In this report 100 patients met the inclusion criteria.
      Patients who suffered from itch were also assessed with the use of a validated
      questionnaire and a modified Skindex-16 questionnaire. We found that the
      prevalence of itch was 66%. Concomitant itch and burning sensation as well as
      itch and pain were noted in 47% and 44% of the patients, respectively. No
      correlation was noted between the severity of these symptoms and the degree of
      venous insufficiency. Itch had a negative impact on quality of life. A limitation
      of this study is that the participants, who were primarily hospital employees,
      are more likely to develop these symptoms. Therefore this study does not reflect
      the true prevalence of these symptoms in the general population. This study found
      that itch, pain, and burning sensation are common symptoms of mild to moderate
      chronic venous insufficiency with a significant impact on quality of life.

PMID- 16112364
TI  - Self-treatment of a basal cell carcinoma with "black and yellow salve".
AB  - Patients may seek "alternative" or "non-traditional" therapies for dermatologic
      problems, frequently in search of a miraculous cure. However, many of these
      medicaments contain unknown compounds with questionable benefit and a potential
      for significant harm. We describe a patient who developed a large ulceration on
      her nose after applying "black and yellow salves" obtained from Mexico in an
      attempt to self-treat a basal cell carcinoma.

PMID- 16112365
TI  - Cutaneous lymphoid hyperplasia and marginal zone B-cell lymphoma following
      vaccination.
AB  - Atypical lymphoid infiltrations arose within the influenza inoculation sites of
      two adult female patients. One patient developed a low-grade cutaneous marginal
      zone B-cell lymphoma (MZL) that was responsive to local excision and radiation
      therapy despite spread to a distant cutaneous site. The second patient's clinical
      course was characterized by a locally aggressive, histologically reactive
      inflammatory reaction responsive only to radiation therapy after multiple failed
      attempts at surgical resection.

PMID- 16112366
TI  - IgG autoantibodies to type VII collagen and an exclusive IgG3 reactivity to the
      laminin alpha3 chain in a patient with an autoimmune subepidermal blistering
      disease.
AB  - We describe a patient with widespread skin lesions and circulating IgG
      autoantibodies to both type VII collagen and laminin 5. Although autoantibodies
      to type VII collagen belonged to IgG2, IgG3, and IgG4 subclasses, laminin 5 was
      targeted exclusively by IgG3 autoantibodies. Interestingly, despite the presence
      of IgG3 autoantibodies, the patient's serum failed to fix complement to the
      dermoepidermal junction. In addition, these autoantibodies did not recruit and
      activate leukocytes or induce dermoepidermal separation in skin sectioned by
      cryostat. We report a most unusual case of an autoimmune subepidermal blistering
      with an exclusive IgG3 reactivity to laminin 5.

PMID- 16112367
TI  - Escharotic agents, Fred Mohs, and Harry Hoxsey.

PMID- 16112368
TI  - Treatment of basal cell carcinoma with dobesilate.

PMID- 16112369
TI  - Retroperitoneal non-Hodgkin's lymphoma presenting as periumbilical erythema.

PMID- 16112370
TI  - Neural fibrolipoma.

PMID- 16112371
TI  - Serpentine supravenous streaks induced by 5-fluorouracil.

PMID- 16112372
TI  - Familial anterior cervical hypertrichosis.

PMID- 16112373
TI  - Elevated levels of serum carcinoembryonic antigen in a patient with eruptive
      syringoma.

PMID- 16112374
TI  - Disseminated granuloma annulare responsive to narrowband ultraviolet B therapy.

PMID- 16112375
TI  - Nail deformity associated with hereditary multiple exostoses.

PMID- 16112376
TI  - Early B-cell chronic lymphocytic leukemia presenting as cutaneous lesions with a
      normal peripheral blood lymphocyte count.

PMID- 16112377
TI  - Phakomatosis pigmentovascularis type IIIb: a case associated with Sturge-Weber
      and Klippel-Trenaunay syndromes.

PMID- 16112378
TI  - Eccrine poroma in an unusual site: a clinical and dermoscopic simulator of
      amelanotic melanoma.

PMID- 16112379
TI  - Rapid response of IgA pemphigus of the subcorneal pustular dermatosis subtype to
      treatment with adalimumab and mycophenolate mofetil.

PMID- 16112380
TI  - Habit-tic-like and median nail-like dystrophies treated with multivitamins.

PMID- 16112381
TI  - Disseminated candidiasis mimicking leukocytoclastic vasculitis.

PMID- 16112382
TI  - Which nevus or that nevus?

PMID- 16112385
TI  - Prednisolone dosage in pemphigus vulgaris.

PMID- 16112384
TI  - Psoriasis Area and Severity Index 50 as an endpoint in psoriasis trials: an
      unconvincing proposal.

PMID- 16112386
TI  - Detecting correlation between sequence and expression divergences in a
      comparative analysis of human serpin genes.
AB  - Physiological functions and characteristic structures of the serpin gene
      superfamily have been studied extensively, yet the evolution of the serpin genes
      remains unclear. Gene duplication in this superfamily may shed light on this
      issue. Two models are used to predict the preservation of duplicated genes: the
      classical model and the duplication-degeneration-complementation (DDC) model. In
      this study, we analyzed the phylogenetic relationships of 33 human serpin genes
      and the expression data of some members of the serpin superfamily from a DNA
      microarray of human leukemia U937 cells with stably inducible expression of the
      leukemia-related AML1-ETO gene. We then determined the utility of the DDC model
      by mapping serpin superfamily expression data to the phylogenetic tree. The
      correlation between sequence and expression divergences as measured by the
      Pearson correlation coefficient indicated that human serpin genes evolved under
      the DDC model. Our study provides a new strategy for comparative analysis of gene
      sequences and microarray data.

PMID- 16112387
TI  - Role of nutrient bound of prey on the dynamics of predator-mediated competitive
      coexistence.
AB  - The coexistence of competitive species with a shared predator is well
      established. The effect of 'food-value' on predator-prey dynamics has also
      received much attention. However, the study of a nutrient bound of prey,
      specifically on predator-mediated competitive-coexistence has not received much
      attention. Here we study the effects of the caloric content or a nutrient bound
      of prey on the dynamics of competitive-coexistence with the shared predator in a
      specific model. We propose and analyze a mathematical model for exploitative
      competition of two prey species with a shared predator. The change of dynamic
      stability due to the variation of a nutrient bound of each prey on predator
      mediated dynamics is studied through extensive numerical experiments. Our
      analytical and numerical results demonstrate that variation in a nutrient bound
      promotes the switching of dynamics and may be treated as a driving force for the
      dynamics of competitive-coexistence with the shared predator.

PMID- 16112388
TI  - Pseudo-spin model for the microtubule wall in external field.
AB  - Microtubules (MTs) in the cytoskeletons of eukaryotic cells provide a wide range
      of microskeletal and micromuscular functionalities. Some evidence has indicated
      that they can serve as a medium for intracellular signaling processing. In this
      paper, for the inherent symmetry structures and the electric properties of
      tubulin dimers, the microtubule (MT) is treated as a one-dimensional
      ferroelectric system. The nonlinear dynamics of the dimer electric dipoles is
      described by virtue of the double-well potential and the physical problem is
      further mapped onto the pseudo-spin system. In addition, the effect of the
      external electric field on the MT has been taken into account.

PMID- 16112389
TI  - Bio-computational model of object-recognition: quantum Hebbian processing with
      neurally shaped Gabor wavelets.
AB  - Theoretical and simulational evidence, as well as experimental indications, are
      accumulating that quantum associative memory and imaging are possible. We compare
      these data with biological evidence, since we find them to a significant extent
      compatible. This paper presents a computationally implementable integrative model
      of appearance-based viewpoint-invariant recognition of objects. The neuro-quantum
      hybrid model incorporates neural processing up to V1 and quantum associative
      processing in V1, achieving together an object-recognition result in V2 and ITC.
      Results of our simulation of the central quantum-like parts of the bio-model,
      receiving neurally pre-processed inputs, are presented. This part contains our
      original simulated storage by multiple quantum interference of image-encoding
      Gabor wavelets done in a Hebbian way, especially using the Griniasty et al. pose
      sequence learning rule.

PMID- 16112390
TI  - Ultrastructural effects of antimicrobial peptides from bovine lactoferrin on the
      membranes of Candida albicans and Escherichia coli.
AB  - Antimicrobial peptides allegedly exert their action on microbial membranes.
      Bovine lactoferrin enfold two antimicrobial domains, lactoferricin B (LFcin B)
      and lactoferrampin (LFampin). Effects of representative peptides thereof on the
      membranes of Candida albicans and Escherichia coli were investigated. Confocal
      laser scanning microscopy revealed that these peptides were internalized within a
      few minutes, concurrently with disrupting membrane integrity as indicated by
      freeze-fracture transmission electron microscopy. The most striking findings were
      induction of distinct vesicle-like structures in the membrane of C. albicans by
      the LFampin peptide, and detachment of the outer membrane and surface protrusions
      in E. coli by the LFcin B peptide.

PMID- 16112391
TI  - The mimetics of antiadhesive peptides as the inhibitors of Mycobacterium kansasii
      phagocytosis.
AB  - The alpha-guanidino acids derived of 15 proteinaceous amino acids, omega
      guanidino acids with gradually increased hydrocarbon chains, and amidinated
      dipeptides, were tested as the mimetics of antiadhesive peptides in Mycobacteria
      phagocytosis inhibition. The crystal structure of omega-guanidino acids used was
      determined by X-ray structural analysis. It follows from our experiments that the
      proper distance between guanidine and carboxyl groups of effector molecules is of
      decisive importance for their inhibitory activity.

PMID- 16112392
TI  - Two proline-rich peptides from pig (Sus scrofa) salivary glands generated by pre
      secretory pathway underlying the action of a proteinase cleaving ProAla bonds.
AB  - The primary structures of two salivary proline-rich peptides (PRP-SP-A, M 6156.0
      amu and PRP-SP-B, M 1905.0 amu), from pig (Sus scrofa) were determined. The PRP
      SP-B peptide, 21 residues long, overlaps with a sequence repeated 43 times in
      three deposited cDNAs coding for PRP proteins cloned from porcine parotid glands
      (Swiss-Prot codes: Q95JC9, Q95JD1, Q95JD0). PRP-SP-A peptide, 56 amino acid
      residues long, overlaps with the N-terminus repeats of Q95JC9 and Q95JD1 and it
      is phosphorylated at Ser 12 and 14. The two peptides were found both in whole
      saliva and in granules from pig parotid glands. The biosynthesis of the two
      peptides implies the action of a proteinase responsible for Pro downward arrow
      Ala cleavage in the pre-secretory process.

PMID- 16112393
TI  - Camptothecin-somatostatin conjugates inhibit the growth of small cell lung cancer
      cells.
AB  - The effects of camptothecin-somatostatin (CPT-SS) conjugates were investigated on
      small cell lung cancer (SCLC) cells. CPT was coupled to a SS agonist (SSA), c(Cys
      Phe-DTrp-Lys-Thr-Cys)Thr-NH2 using the built in nucleophile assisted-releasing
      group (L1) N-methyl-aminoethyl-Gly-Dser-Nle-Dtyr-Dser or (L2) aminoethyl-Gly-Dser
      Nle-Dtyr-Dser. The resulting CPT-L1-SSA and CPT-L2-SSA inhibited the specific
      binding of [125I-Tyr11]SS to NCI-H69 cell membranes with IC50 values of 0.2 and
      2.1 nM, respectively. [125I]CPT-L1-SSA was internalized by SCLC cells at 37
      degrees C but not at 4 degrees C. CPT-L1-SSA and CPT-L2-SSA inhibited in a dose
      dependent manner the increase in adenylylcyclase activity caused by 25 microM
      forskolin. In vitro, 0.3 microM CPT-L1-SSA half-maximally inhibited the clonal
      growth of SCLC cells and 1 microM CPT-L1-SSA strongly inhibited 3H-thymidine
      incorporation into DNA and trypan-blue exclusion. These results suggest that CPT
      conjugated peptides such as CPT-L1-SSA may prove useful for exploring the
      efficacy of receptor-directed cytotoxicity to inhibit the proliferation of SCLC
      cells.

PMID- 16112394
TI  - Potential role of the neuropeptide CGRP in the induction of differentiation of
      rat hepatic portal vein wall.
AB  - The media of the rat hepatic portal vein is composed of an internal circular
      muscular layer (CL) and an external longitudinal muscular layer (LL). These two
      perpendicular layers differentiate progressively from mesenchymal cells within
      the first month after birth. In this paper, we studied the development of
      calcitonin gene-related peptide (CGRP) innervation during post-natal
      differentiation of the vessel. We show that CGRP innervation is already present
      around the vessel at birth in the future adventitia but far from the lumen of the
      vessel. Progressively, CGRP immunoreactive fibers reached first LL then CL. CL by
      itself become only innervated at day 14 after birth. This corresponds to the time
      at which thick filaments (myosin) are visible in electron microscopy and desmin
      visualisable by immunocytochemistry. Furthermore, we provide evidence by
      autoradiography, that binding sites for CGRP are transiently expressed on the
      portal vein media at day 1 and 14 after birth. Vascular smooth muscle cells were
      transfected with constructs containing promoters for desmin or smooth muscle
      myosin heavy chain (smMHC). CGRP treatment of the cells significantly increased
      the expression of smMHC. Overall these results suggest that CGRP can potentially
      influence the differentiation of smooth muscle cells from the vessel wall.

PMID- 16112395
TI  - Central thyrotropin-releasing hormone increases hepatic cyclic AMP through vagal
      cholinergic and prostaglandin-dependent pathways in rats.
AB  - Central neuropeptides play roles in many physiologic regulations through the
      autonomic nervous system. We have demonstrated that central thyrotropin-releasing
      hormone (TRH), one of neuropeptides, induces a stimulation of hepatic
      proliferation through vagal-cholinergic pathways. Since cAMP is known to play an
      important role in the hepatic proliferation, effect of central TRH on hepatic
      cAMP was investigated. Rats were intracisternally injected with either a TRH
      analog, RX-77368 (1-100 ng), or saline. The liver was removed 2-72 h after the
      TRH analog and hepatic cAMP content was determined by radioimmunoassay. In some
      experiments, pretreatment with hepatic vagotomy, atropine methyl nitrate, or 6
      hydroxydopamine (6-OHDA) was performed. Hepatic cAMP was dose-dependently
      increased by intracisternal TRH analog (5-100 ng) with a peak response occurring
      12 h postinjection. The central TRH-induced increase in hepatic cAMP was
      abolished by vagotomy, atropine and indomethacin, but not by 6-OHDA. Intravenous
      injection of the TRH analog (10 ng) did not affect hepatic cAMP. These results
      demonstrate that TRH acts in the brain to increase hepatic cAMP through vagal
      cholinergic and prostaglandin-dependent pathways, suggesting that central TRH
      modulates hepatic functions through cAMP-mediated signaling pathways.

PMID- 16112396
TI  - Role of gastric mast cells in the regulation of central TRH analog-induced
      hyperemia in rats.
AB  - RX 77368 (RX) increases gastric mucosal blood flow by a vagal cholinergic
      mechanism. The relative roles of mucosal and connective tissue mast cells (MMC
      and CTMC) were investigated in RX-injected rats. Blood flow and mast cell
      degranulation were measured after intracisternal RX. RX significantly increased
      gastric mucosal blood flow, and sequentially degranulated CTMC and MMC. Ketotifen
      or doxantrazole inhibited the hyperemic response. Ondansetron, RS-039604-90, or
      famotidine, but not ketanserin or pyrilamine, reduced hyperemia. Mast cells
      mediate RX-induced gastric hyperemia via 5-HT3, 5-HT4, and H2 receptors; initial
      increase depends upon CTMC whereas MMC contributes to the later response.

PMID- 16112397
TI  - The effects of [Arg14, Lys15] nociceptin/orphanin FQ, a highly potent agonist of
      the NOP receptor, on in vitro and in vivo gastrointestinal functions.
AB  - Nociceptin/orphanin FQ (N/OFQ) administered into the lateral left cerebral
      ventricle of rats has been reported to inhibit in vivo gut motor and secretory
      functions. Recently, a novel N/OFQ analog, [Arg14, Lys15] N/OFQ, was synthesized
      and demonstrated to behave as a highly potent agonist at the human recombinant
      N/OFQ peptide (NOP) receptors and to produce long-lasting effects in vivo in mice
      compared with the natural ligand N/OFQ. In the present study, the pharmacological
      profile of [Arg14, Lys15] N/OFQ was further evaluated and compared with that of
      N/OFQ in vitro on guinea pig exocrine pancreas and in vivo on gastric emptying,
      colonic propulsion and gastric acid secretion in rats. [Arg14, Lys15] N/OFQ and
      N/OFQ significantly decreased the KCl-evoked amylase secretion from isolated
      pancreatic lobules of the guinea pig. In in vivo experiments, [Arg14, Lys15]
      N/OFQ mimicked the effects of N/OFQ, inducing, after intracerebroventricular
      injection, a delay (up to 70%) in the gastric emptying of a phenol red meal, an
      increase (about 40 times) of the mean bead colonic expulsion time and a decrease
      (up to 90%) of gastric acid secretion in water loaded rats after 90 min pylorus
      ligature. In all these assays, [Arg14, Lys15] N/OFQ was more effective than
      N/OFQ, and its effective doses were at least 10-fold lower than N/OFQ effective
      doses. The highly selective NOP receptor antagonist, UFP-101, decreased the
      efficacy of [Arg14, Lys15] N/OFQ in in vitro and in vivo assays above reported.
      These findings: (a) show that pancreatic NOP receptors mediate an in vitro
      inhibitory effect on stimulated guinea pig amylase secretion; (b) confirm that
      the stimulation of central NOP receptors exerts an inhibitory control on gastric
      emptying, colonic motility and gastric secretion in rats and (c) put in evidence
      that [Arg14, Lys15] N/OFQ, being more potent and effective than the natural
      ligand N/OFQ, represents a new pharmacological tool for the study of the
      physiological and pharmacological roles mediated by the N/OFQ-NOP receptor
      system.

PMID- 16112398
TI  - Gastrokinetic effect of ghrelin analog RC-1139 in the rat. Effect on post
      operative and on morphine induced ileus.
AB  - We aimed to confirm the gastrokinetic effect of ghrelin analog, RC-1139, in the
      presence of opiates. Gastric emptying was verified in rats by counting stomach
      residue 15 min after gavage of methylcellulose. Normal rats: RC-1139 (0, 0.25,
      1.0, 2.5 mg/kg i.v.) decreased methylcellulose left in stomach (47, 36, 12, 10%
      of ingested solution). Post-operative ileus (post-op. ileus) ileus: gastric
      residue decreased from 88 to 66, 53, 51% with RC-1139 0, 1.0, 2.5, 10 mg/kg.
      Morphine in post-op. ileus: gastroparesis was corrected at 10 mg/kg (54%).
      Ghrelin analog RC-1139 is a potent gastrokinetic in rat; it reversed gastric post
      op. ileus, even in the presence of opiates.

PMID- 16112399
TI  - The interoceptive cue properties of ghrelin generalize to cues produced by food
      deprivation.
AB  - A number of recent studies implicate the gut-brain peptide ghrelin as a putative
      "hunger signal". Most of these studies, however, rely on either consummatory
      behavior (in humans or nonhuman animals) or self-report (in humans) to draw
      conclusions regarding the orexigenic properties of this peptide. The present
      study employs the deprivation intensity discrimination paradigm to assess the
      interoceptive sensory properties of ghrelin in rats. In this paradigm, one group
      of rats was placed in a training context and presented with sucrose pellets when
      24 h food deprived, but not when 1 h food deprived (24+ group). A second group
      was trained using the opposite sucrose-deprivation level contingency (1+ group).
      Learning in this paradigm was demonstrated by animals approaching the food
      delivery location more frequently under their rewarded compared to their non
      rewarded deprivation condition (prior to actual pellet delivery). After
      asymptotic performance of this discrimination was achieved, these animals (1 h
      food deprived) were administered ghrelin or saline, either i.p. (3 or 6 nmol) or
      i3vt (0.1 or 1 nmol), placed in the training context, and appetitive responses
      were measured. Testing was conducted in extinction, eliminating confounding
      effects of food consumption. Results of these tests showed that 6 nmol i.p.
      ghrelin and 0.1 and 1 nmol i3vt ghrelin all generalized to a state of 24 h food
      deprivation, indicating that exogenous ghrelin has sensory properties in common
      with the stimuli produced by 24 h food deprivation. These results support the
      notion that endogenous ghrelin contributes to an interoceptive hunger cue, and
      that this may be a mechanism by which ghrelin influences food intake and
      appetitive behavior.

PMID- 16112400
TI  - Inhibitory effects of pituitary adenylate cyclase-activating polypeptide (PACAP)
      and vasoactive intestinal peptide (VIP) on food intake in the goldfish, Carassius
      auratus.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has a similar
      structure to that of vasoactive intestinal peptide (VIP) and both the
      polypeptides belong to the same molecular group, the secretin-glucagon
      superfamily. PACAP and VIP have possible potency as hypothalamic factors
      mediating the release of pituitary hormones in the fish pituitary. However, the
      roles of PACAP and VIP in the central nervous systems of fish have not yet been
      made clear. Recently, it was reported that PACAP and/or VIP are involved in the
      feeding behavior of the mouse and chick. Therefore, we investigated the effects
      of intracerebroventricular (ICV) and intraperitoneal (IP) administration of
      synthetic PACAP and VIP on food intake in the goldfish, Carassius auratus.
      Cumulative food intake was significantly decreased by ICV injection of PACAP (11
      or 22 pmol/g body weight) or VIP (11 or 22 pmol/g) during a 60-min observation
      period after treatment. IP administration of PACAP (44 or 88 pmol/g) or VIP (22
      or 44 pmol/g) induced a significant decrease in food intake during a 60-min
      observation period after treatment. These results suggest that PACAP and VIP may
      be involved as feeding regulators in goldfish.

PMID- 16112401
TI  - Cholecystokinin-8 increases Fos-like immunoreactivity in the brainstem and
      myenteric neurons of rats through CCK1 receptors.
AB  - To examine the role of cholecystokinin1 receptor (CCK1) in the activation of
      brainstem and myenteric neurons by CCK, we compared the ability of exogenous CCK
      8 to induce Fos-like immunoreactivity (Fos-LI) in these neurons in Otsuka Long
      Evans Tokushima Fatty (OLETF) rats, lacking CCK1 receptors, and Long-Evans
      Tokushima Otsuka (LETO) controls. Five groups (n=4 rats per group) of OLETF rats,
      and five LETO control groups, were injected intraperitoneally (IP) with 5, 10,
      20, and 40 microg/kg CCK-8 or saline. Forty-micrometer brainstem sections
      containing the area postrema, nucleus of the solitary tract, and the dorsal motor
      nucleus of the vagus, and myenteric neurons of the duodenum, jejunum, and ileum
      underwent a diaminobenzidine reaction enhanced with nickel to reveal Fos-LI. CCK
      8 did not increase Fos-LI in any of the tested neurons in the OLETF rats. CCK-8
      increased Fos-LI in the brainstem of the LETO rats in a dose dependent manner. In
      the LETO rats only 40 microg/kg CCK-8 increased Fos-LI in the myenteric plexus of
      the jejunum. This study demonstrates that CCK-8 activates the brainstem and
      myenteric neurons through the CCK1 receptor.

PMID- 16112402
TI  - Energy expenditure by intravenous administration of glucagon-like peptide-1
      mediated by the lower brainstem and sympathoadrenal system.
AB  - Glucagon-like peptide-1 (GLP-1) is released from the gut in response to nutrient
      ingestion. Intravenous (iv) administration of GLP-1 (50 pmol-20 nmol) elicited
      dose-dependent increases in the rate of whole-body O2 consumption (VO2), an index
      of energy expenditure, and heart rate of urethane-anesthetized rats. The body
      core (colonic) temperature increased up to 0.3 degrees C without accompanying
      alteration of tail skin temperature. Intracerebroventricular (icv) administration
      of GLP-1 induced a slower and smaller increase in VO2 than the intravenous
      administration. The injection of glucagon-like peptide-2 (iv or icv) had no
      effect on VO2, body temperatures, or heart rate. Decerebration had no effect on
      the thermogenic responses induced by the iv administration of GLP-1, suggesting
      that the forebrain is not essential for these responses. However, cervical spinal
      transection greatly attenuated the responses, suggesting the critical involvement
      of the lower brainstem. Adrenalectomy or pretreatment with an autonomic ganglion
      blocker, hexamethonium, or a beta-adrenergic blocker, propranolol, also
      significantly attenuated the thermogenic response. However, subdiaphragmatic
      vagotomy or celiac-superior mesenteric ganglionectomy had no effect. Rats made
      insulin-deficient by pretreatment with streptozotocin also exhibited the normal
      thermogenic response to GLP-1. These results suggest the involvement of the GLP-1
      in postprandial energy expenditure, mediated by the lower brainstem and
      sympathoadrenal system.

PMID- 16112403
TI  - Effect of relaxin on myocardial ischemia injury induced by isoproterenol.
AB  - The omnipresent 6-kDa polypeptide relaxin (RLX) is emerging as a multifunctional
      endocrine and paracrine factor in a broad range of target tissues including
      cardiovascular tissues. To explore the pathophysiological roles of RLX in
      ischemic cardiovascular diseases, we studied the changes in RLX mRNA level in the
      myocardium and the effect of RLX supplements in rats with isoproterenol (ISO)
      induced myocardial injury. In ISO-treated rats, RLX levels in myocardia and
      plasma increased 3.7- and 6.9-fold, respectively (P<0.01), the mRNA level
      increased significantly in myocardia compared with controls. Co-administration of
      RLX (0.2 and 2.0 microg/kg/d) and ISO increased left-ventricular pressure
      development and decreased left ventricular end-diastolic pressure (LVDEP) (all
      P<0.01). Malondialdehyde content in myocardia and lactate dehydrogenase and
      creatine phosphokinase activities in plasma in RLX-treated rats decreased
      markedly compared with that in ISO-treated alone rats (P<0.01 or P<0.05). In the
      high-dose RLX group, fibroblastic hyperplasia was relieved in myocardia,
      hydroxyproline level was lower, by 33% (P<0.05), and endothelin content in plasma
      was lower, by 31% (P<0.01) than in the ISO-alone group. Compared with control
      group, any indexes in sham rats treated with high-dose RLX were unaltered (all
      P>0.05). These results showed an up-regulation of myocardial RLX during ISO
      induced myocardial ischemia injury and the protective effect of RLX on ISO
      induced cardiac inhibition and fibrosis, which suggests that RLX could be an
      endogenous cardioprotective factor in ischemic heart diseases.

PMID- 16112404
TI  - Cardiovascular effects of newly discovered peptide intermedin/adrenomedullin 2.
AB  - Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related
      peptide (CGRP). The present study aimed to investigate the cardiovascular effects
      of IMDs (IMD1-47 and IMD8-47) in rats. Intravenous administration of 150 nmol
      IMDs continuously decreased mean arterial pressure and inhibited cardiac
      function. Administration with IMDs decreased left ventricular end-systolic
      pressure (LVESP) and maximal rate of left-ventricle pressure development (+/
      LVdp/dt(max)), and elevated left ventricular end-diastolic pressure (LVEDP).
      Changes with IMD1-47 treatment were close to that with IMD8-47 (P>0.05).
      Perfusion of isolated rat hearts in vitro with IMD8-47 (10(-8) and 10(-7)mol/L)
      resulted in lower LVSP, by 40 and 56% (P<0.01); lower +LVdp/dt (max), by 33 and
      47% (P<0.01); lower -LVdp/dt(max), by 25 and 39% (P<0.01); but higher coronary
      perfusion flow (CPF), by 25% (P<0.05) and 33% (P<0.01), respectively, than
      controls. However, both IMD8-47 and IMD1-47 (from 10(-13) to 10(-7)mol/L) relaxed
      preconstricted aortic rings in a dose-dependent manner. Intravenous
      administration of IMD1-47 and IMD8-47 (10(-7)mol/L) in vivo increased the cyclic
      adenosine monophosphate (cAMP) content by 68 and 150% (both P<0.01),
      respectively, in myocardia and 320 and 281% (both P<0.01), respectively, in
      aortas, compared with controls. Perfusion of isolated hearts with IMD1-47 and
      IMD8-47 (10(-7)mol/L) enhanced cAMP content by 24% (P<0.05) and 73% (P<0.01),
      respectively, compared with controls. IMDs inhibited 3H-Leucine incorporation in
      cardiomyocytes in a concentration-dependent manner. IMD1-47 and IMD8-47 (10(-7)
      and 10(-8)mol/L) decreased 3H-Leucine incorporation by 12-25% (P<0.01) and 14-18%
      (P<0.01), respectively. IMD mRNA was detected in cultured neonatal cardiomyocytes
      and isoproterenol-induced hypertrophic myocardia but not normal myocardia of
      adult rats. These results suggest that IMD might be a regulatory factor for
      cardiovascular function and myocardial hypertrophy as a cardiovascular active
      peptide.

PMID- 16112405
TI  - Coexpression of AT1 and AT2 receptors by human fibroblasts is associated with
      resistance to angiotensin II.
AB  - Angiotensin II (AngII) is considered as a cytokine-like factor displaying a
      variety of proinflammatory and profibrotic cellular effects. Most of these
      effects seem mediated by AT1 signaling, whereas AT2 expression and function in
      adult human cells remain unclear. We have studied AT1 and AT2 expression in
      different human adult fibroblasts types and analyze their response to AngII.
      AngII did not induce thymidine incorporation, apoptosis nor collagen gene or
      protein expression in human fibroblasts. Specific AT1 or AT2 inhibitors did not
      modify this apparent resistance to AngII. We found abundant expression of both
      AT1 and AT2 receptors in all human fibroblasts studied, whereas vascular smooth
      muscle cells (VSMC) which only expressed AT1 receptor, displayed a clear AT1
      dependent proliferative response to AngII. These data demonstrate that cultured
      human adult fibroblasts express both AT1 and AT2 receptor types and this
      phenomenon is associated with a lack of growth or collagen synthesis responses to
      AngII.

PMID- 16112406
TI  - Obstructive sleep apnea: Plasma endothelin-1 precursor but not endothelin-1
      levels are elevated and decline with nasal continuous positive airway pressure.
AB  - Assessment of plasma endothelin-1 (ET-1) reveals conflicting results in cerebral
      and noncerebral conditions. Obstructive sleep apnea (OSA) syndrome has been used
      as a definite challenge for the investigation of endothelin measurements. Despite
      marked sleep-related breathing disturbances in untreated patients peripherally
      measurable ET-1 concentrations remained within the normal range and did not
      change after an appropriate therapy with continuous positive airway pressure
      (CPAP). In contrast, its precursor, big ET-1, was considerably elevated in
      untreated patients and dropped to normal values after long-term CPAP depending on
      compliance. Relatively stable big ET-1 elevations in untreated patients, during
      sleep and wakefulness, suggest that a general endothelial alteration beyond that
      explained by a direct impact of nocturnal breathing disturbances on the vascular
      system occurs. CPAP-therapy effectively lowered plasma big ET-1 in compliant
      patients and thus possibly their related risk for vascular diseases. Big ET-1 has
      been demonstrated to be a more appropriate marker of endothelial alteration than
      ET-1 because of its longer half-life. Simultaneous measurements are to be
      recommended.

PMID- 16112407
TI  - The effects of arg-vasopressin on osteoblast-like cells in endothelial nitric
      oxide synthase-knockout mice and their wild type counterparts.
AB  - In the present study, we investigated whether nitric oxide (NO) could be involved
      in the effects of arg-vasopressin (AVP) on osteoblast-like cells. Cells derived
      from endothelial nitric oxide synthase (eNOS)-knockout mice and their wild type
      (WT) counterparts, and an osteosarcoma cell line (SaOS-2) were used. AVP (10-100
      pmol/l) increased proliferation of osteoblast-like cells from WT mice. The effect
      was abolished by an AVP V1-receptor antagonist. AVP increased proliferation of
      cells from eNOSKO mice only when a NO donor, SNAP, was added. A nitric oxide
      synthase-inhibitor, L-NAME, antagonized the increase in cell proliferation in
      response to AVP in SaOS-2 cells. In conclusion, this study indicates that NO is
      involved in the effects of AVP on cell proliferation in osteoblast-like cells.

PMID- 16112408
TI  - Endomorphins interact with tachykinin receptors.
AB  - Soon after the discovery of endomorphins several studies indicated differences
      between pharmacological effects of endomorphins and other MOR selective ligands,
      as well as differences between the effects of endomorphin I and endomorphin II.
      We now propose that these differences are the result of an additional non-opioid
      property of endomorphins, namely, their weak antagonist properties with respect
      to tachykinin NK1 and NK1 receptors.

PMID- 16112409
TI  - The role of adrenomedullin in angiogenesis.
AB  - Adrenomedullin (AM) is a 52 amino acid peptide originally isolated from human
      pheochromocytoma. It was initially demonstrated to have profound effects in
      vascular cell biology, since AM protects endothelial cells from apoptosis,
      promotes angiogenesis and affects vascular tone and permeability. This review
      article summarizes the literature data concerning the relationship between AM and
      angiogenesis and describes the relationship between vascular endothelial growth
      factor, hypoxia and AM and tumor angiogenesis. Finally, the role of AM as a
      potential target of antiangiogenic therapy is discussed.

PMID- 16112410
TI  - Calcitonin gene-related peptide and hypertension.
AB  - Capsaicin-sensitive sensory nerves participate in the regulation of
      cardiovascular functions both in the normal state and the pathophysiology of
      hypertension through the actions of potent vasodilator neuropeptides, including
      calcitonin gene-related peptide (CGRP). CGRP, a very potent vasodilator, is the
      predominant neurotransmitter in capsaicin-sensitive sensory nerves, and plays an
      important role in the initiation, progression and maintenance of hypertension
      via: (1) the alterations in its synthesis and release and/or in vascular
      sensitivity response to it; (2) interactions with pro-hypertensive systems,
      including renin-angiotensin-aldosterone system, sympathetic nervous system and
      endothelin system; and (3) anti-hypertrophy and anti-proliferation of vascular
      smooth muscle cells. The decrease in CGRP synthesis and release contributes to
      the elevated blood pressure, as shown in the spontaneously hypertensive rats,
      alpha-CGRP knockout mice, Dahl-salt or phenol-induced hypertensive rats. In
      contrast, the increase in CGRP levels or the enhancement of vascular sensitivity
      response to CGRP plays a beneficial compensatory depressor role in the
      development of hypertension, as shown in deoxycorticosterone-salt, sub-total
      nephrectomy-salt, N(omega)-nitro-L-arginine methyl ester or two-kidney, one-clip
      models of hypertension in rats. We found that rutaecarpine causes a sustained
      depressor action by stimulation of CGRP synthesis and release via activation of
      vanilloid receptor subtype 1 (VR1) in hypertensive rats, which reveals the
      therapeutic implications of VR1 agonists for treatment of hypertension.

PMID- 16112411
TI  - Camptocormia or Pisa syndrome in multiple system atrophy.
AB  - Although a mild stooped posture is a hallmark of parkinsonism, extreme trunk
      forward flexion is not common. This phenomenon was described in different
      etiological entities and called camptocormia. Other similar presentations called
      Pisa syndrome and antecollis were described mainly in extrapyramidal disorders.
      Authors present two cases of probable multiple system atrophy (MSA) with
      predominant parkinsonism and Pisa syndrome (or camptocormia). Both of them were
      previously misdiagnosed as idiopathic Parkinson's disease (PD) and one was
      reported 1 year earlier. The typical clinical presentation fulfilling the
      diagnostic criteria for multiple system atrophy, rapid progression with lack of
      responsiveness to L-DOPA and apomorphine and typical MRI putaminal pathology
      observed in both cases allowed us to make a diagnosis. Accuracy of clinical
      diagnosis in multiple system atrophy is still very poor. Therefore, unusual or
      rare clinical presentations may support the final diagnosis. The camptocormia,
      Pisa syndrome and antecollis may represent the continuum of the same motor
      phenomenon and most of the authors refer them to unusual form of axial dystonia.
      According to many clinical presentations on different forms of camptocormia/Pisa
      syndrome authors conclude that not etiology, but the localization of specific
      lesion, probably within putamen is responsible for that form of dystonia. In
      cases of parkinsonism and severe forward flexion of trunk multiple system
      atrophy, diagnosis should be considered.

PMID- 16112412
TI  - Hedgehog signaling pathway as a therapeutic target in breast cancer.
AB  - The Hedgehog (Hh) signaling pathway, which is well conserved even in mammals and
      other vertebrate species, has long been known to direct growth and patterning
      during embryonic development. It has been shown that the Hh pathway also plays a
      critical role in mouse normal mammary gland development. Namely, it has been
      shown that disruption of the Hh pathway-related genes such as Patched-1 and Gli2
      leads to ductal dysplasias that closely resemble some hyperplasia of human
      breast. In addition, it has been reported that breast carcinoma cells have
      disruption of these genes. These findings strongly indicate a contribution of the
      Hh pathway to development of human breast carcinoma. In fact, constitutive
      activation of the Hh pathway was found in most of 52 surgically resected breast
      carcinoma specimens. Interestingly, exposure to cyclopamine, a steroidal alkaroid
      that blocks the Hh pathway, suppressed the growth of the Hh pathway-activated
      breast carcinoma cells. Thus, the Hh pathway may function in progression of
      breast carcinoma. In this short review, possibilities of the Hh pathway as a new
      therapeutic target in breast carcinoma will be mainly discussed.

PMID- 16112413
TI  - The Ataxia-telangiectasia mutated gene and breast cancer: gene expression
      profiles and sequence variants.
AB  - The role of the Ataxia-telangiectaisa mutated (ATM) gene, as a risk factor for
      breast cancer has been a consistent theme in the literature since the first
      reports by Swift and colleagues who reported that ATM heterozygotes in AT
      families had increased risks of developing breast cancer. Loss of heterozygosity
      at the ATM locus has been reported in 30-40% of breast tumours and 50-70% show
      altered ATM protein levels. Germline ATM sequence variants have been reported in
      breast cancer cases, however, it is difficult to fully evaluate the increased
      risk associated with their presence. The potential role of such variants needs to
      be further assessed, together with functional studies to model their impact on
      ATM function.

PMID- 16112414
TI  - Cytochrome P450-mediated metabolism of estrogens and its regulation in human.
AB  - Estrogens are eliminated from the body by metabolic conversion to estrogenically
      inactive metabolites that are excreted in the urine and/or feces. The first step
      in the metabolism of estrogens is the hydroxylation catalyzed by cytochrome P450
      (CYP) enzymes. Since most CYP isoforms are abundantly expressed in liver, the
      metabolism of estrogens mainly occurs in the liver. A major metabolite of
      estradiol, 2-hydroxyestradiol, is mainly catalyzed by CYP1A2 and CYP3A4 in liver,
      and by CYP1A1 in extrahepatic tissues. However, CYP1B1 which is highly expressed
      in estrogen target tissues including mammary, ovary, and uterus, specifically
      catalyzes the 4-hydroxylation of estradiol. Since 4-hydroxyestradiol generates
      free radicals from the reductive-oxidative cycling with the corresponding
      semiquinone and quinone forms, which cause cellular damage, the specific and
      local formation of 4-hydroxyestradiol is important for breast and endometrial
      carcinogenesis. Changes in the expression level of estrogen-metabolizing CYP
      isoforms not only alter the intensity of the action of estrogen but may also
      alter the profile of its physiological effect in liver and target tissues.
      Generally, many CYP isoforms are induced by the substrates themselves, resulting
      in enhanced metabolism and elimination from the body. Of particular interest is a
      novel finding that human CYP1B1 is regulated by estradiol via the estrogen
      receptor. This fact suggests that the regulation of CYP enzymes involved in
      estrogen metabolism by estrogen itself would be physiologically significant for
      the homeostasis of estrogens at local organs. In this mini-review, we discuss the
      CYP-mediated metabolism of estrogens and the regulation of the estrogen
      metabolizing CYP enzymes in relation to the risk of cancer.

PMID- 16112415
TI  - Protective effects of black tea extract on testosterone induced oxidative damage
      in prostate.
AB  - Since ancient times, antipyretic, anti-inflammatory, antimicrobial and
      antioxidative properties of tea have been recognized. Black tea (Camellia
      sinensis) contains a variety of polyphenolic ingredients including the
      theaflavins (TF), thearubigins (TG) and catechins. Components from black tea have
      been accounted to play an important role in scavenging free radicals generated by
      mutagens and carcinogens. Androgens are the key factors in either the initiation
      or progression of prostate cancer (PCA) by inducing oxidative stress. In the
      present set of investigations, the antioxidative potential of black tea extract
      against androgen mediated oxidative stress in male Wistar rats has been studied.
      Testosterone was given at a dose of 5 mg/kg b.w. subcutaneously, consecutively
      for 5 days. Prior to androgen administration, animals were kept on 0.5, 1.0 and
      1.5% aqueous tea extract (ATE) as sole source of drinking fluid for 15 days. The
      prostate tissue was dissected out for biochemical analysis for antioxidant
      enzymes viz. catalase (CAT), superoxide dismutase (SOD), lipid peroxidation
      (LPO), glutathione-s-transferase (GST) and glutathione reductase (GR). The
      results revealed that testosterone administration induced the oxidative stress in
      rat prostate, however, in 0.5, 1.0 and 1.5% ATE supplemented groups, a
      significant protective effect of black tea against testosterone induced oxidative
      injury was recorded. Hence, the study reveals that constituents present in black
      tea impart protection against androgen induced oxidative injury that may result
      in development of prostate cancer.

PMID- 16112416
TI  - Glutathione peroxidase, glutathione-S-transferase, catalase, xanthine oxidase, Cu
      Zn superoxide dismutase activities, total glutathione, nitric oxide, and
      malondialdehyde levels in erythrocytes of patients with small cell and non-small
      cell lung cancer.
AB  - Lung cancer is a common pathology with high mortality due to late diagnosis.
      Glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), catalase (CAT),
      xanthine oxidase (XO), Cu-Zn superoxide dismutase (Cu-Zn SOD) activities, total
      glutathione (TGSH), nitric oxide (NO*), and malondialdehyde (MDA) levels were
      investigated in erythrocytes of patients with non-small-cell lung cancer (NSCLC)
      and small-cell lung cancer (SCLC), and healthy control group. We aimed to
      investigate serum GSH, GSH-dependent enzymes activities (GSH-Px and GST), XO,
      CAT, Cu-Zn SOD activity, and NO*, and MDA levels in patients with NSCLC and with
      SCLC and correlate with the cancer stage. Erythrocyte MDA, NO*, TGSH levels and
      erythrocyte SOD, CAT and XO activities were significantly higher in patients with
      NSCLC and SCLC than in controls. Slightly increased erythrocyte GSH-Px and GST
      activities were not significantly different from the controls. Erythrocyte MDA
      level positively correlated with erythrocyte NO* levels in patients with early
      stage (I+II) in NSCLC groups. Erythrocyte MDA level positively correlated with
      erythrocyte XO activity in patients with advanced stage (III+IV) in NSCLC groups.
      However, no other correlation could be found among the parameters in healthy
      controls and patients with NSCLC and with SCLC. Results obtained in this study
      indicate significant changes in antioxidant defence system in NSCLC and SCLC
      patients, which may lead to enhanced action of oxygen radical, resulting in lipid
      peroxidation.

PMID- 16112417
TI  - Integrity and stability of the citrulline-arginine pathway in normal and tumour
      cell lines.
AB  - Arginine catabolizing enzymes have been used on cancers for over 60 years. In the
      last 5 years the ability of arginine catabolizing enzymes, not only to inhibit
      proliferation, but to kill tumour cells has been reinvestigated. Selectivity of
      action lies in the inability of many tumours to circumvent arginine deprivation
      by recycling precursors through the urea cycle. While this offers an immediate
      window of opportunity to treat, e.g. melanomas and hepatocellular carcinomas
      (HCC) that have poor citrulline converting ability, it is possible that the
      deprivation can be applied to many other types of cancer. The problem of
      deficiency of the urea cycle enzymes in a wider range of normal and malignant
      cell lines has been addressed, and shown to be variable throughout several
      different tumour types. We also need to know how fickle recycling enzyme activity
      can be in both normal and tumour cells, and found to be remarkable stable.
      Increasing interest is shown in the amino acid (arginine) deprivation protocol
      because it has already moved into the clinic. Initial findings on a named-patient
      basis have been encouraging, and the development of a new rational approach to
      the systemic treatment of melanomas, HCCs and leukemias seems imminent. This is
      the more attractive because arginine deprivation protocols can also 'stage'
      tumour cells for combination therapy in cases where they might not be killed
      outright by deprivation alone.

PMID- 16112418
TI  - Inhibitory effects of costunolide on the telomerase activity in human breast
      carcinoma cells.
AB  - Costunolide, a natural sesquiterpene compound, has been known having cytotoxic
      and chemopreventive effects on various human cancer cells. In the present study,
      we examined the effects of costunolide on telomerase activity and on the
      components of telomerase in MCF-7 (wild-type p53) and MDA-MB-231 (mutant p53)
      cells. We found that costunolide inhibited the growth and telomerase activity of
      MCF-7 and MDA-MB-231 cells in a concentration- and time-dependent manner. The
      expression of hTERT mRNA was also inhibited but hTR mRNA was not. In addition,
      the bindings of transcription factors in hTERT promoters were significantly
      decreased in both cells by the treatment of costunolide. These results suggest
      that costunolide inhibited the growth of both MCF-7 and MDA-MB-231 cells and this
      effect was mediated at least in part by a significant reduction in telomerase
      activity.

PMID- 16112419
TI  - Potent inhibition of human telomerase by helenalin.
AB  - Telomerase activity is repressed in normal human somatic cells, but is activated
      in most cancers, suggesting that telomerase may be an important target for cancer
      therapy. Inhibition of telomerase in cancer cells has been shown to limit the
      growth of human cancer cells in culture. In this study, we report that helenalin,
      a natural sesquiterpene lactone, is a potent and selective inhibitor for human
      telomerase. In vitro studies indicate that this drug can inactivate telomerase
      directly in a manner that is dependent on concentration and time. The inhibitory
      action of this drug on telomerase is selective since the presence of excessive
      externally added proteins did not protect the inhibition and all of the other
      enzymes tested in this study were not inhibited by this drug. Furthermore, we
      demonstrated that helenalin can inhibit the expression of hTERT and telomerase in
      hematopoietic cancer cells. Therefore, the anti-tumor activity of helenalin is
      attributed, at least in part, to the inhibition of telomerase.

PMID- 16112420
TI  - Mapping of the methylation pattern of the MUC2 promoter in pancreatic cancer cell
      lines, using bisulfite genomic sequencing.
AB  - Expression of the MUC2 gene is controlled by the methylation of CpG sites in the
      promoter region, but the detailed methylation status of this region has yet to be
      reported. We have mapped the complete methylation status of the MUC2 promoter
      from position -1989 to position +288 upstream, a region that contains 59 CpG
      sites, using bisulfite genomic sequencing in two pancreatic cancer cell lines
      (PANC1, BxPC3) and in isolated normal colon crypts as a control. The MUC2
      promoter in PANC1, a cell line that does not express MUC2, was highly methylated
      (average 87%, complete methylation at 28 of the 59 CpG sites), while the promoter
      region in the MUC2-expressing BxPC3 cell line (average 43%, complete methylation
      at 2 of 59 CpG sites) and in MUC2-expressing normal colon crypts (average 33%, no
      CpG site was completely methylated) were only partially methylated (P<0.0001). 5
      Aza-2'-deoxycytidine treatment of PANC1 cells reduced the methylation level
      (average 36%) and induced MUC2 mRNA expression. However, mRNA expression of AP2,
      SP1 and CDX2 was not affected by this treatment. Our data provide the first
      detailed methylation map of the MUC2 promoter region for the first time, using
      the conversion-specific bisulfite genomic sequencing. Previously unproven
      methylation sites were detected, and some AP2 and SP1 binding sites showed
      different methylation levels among PANC1, BxPC3 and colonic crypt cells. Our
      mapping data provide an essential basis for further studies of methylation
      regulated MUC2 inactivation.

PMID- 16112421
TI  - The PLAGL1 gene is down-regulated in human extraskeletal myxoid chondrosarcoma
      tumors.
AB  - In approximately 70% of human extraskeletal myxoid chondrosarcoma (EMC) tumors, a
      t(9;22) chromosome translocation gives rise to a fusion protein, named EWS/NOR1,
      containing the amino-terminal domain of EWS fused to the complete amino acid
      sequence of the nuclear receptor NOR1. Several observations suggest that one role
      of EWS/NOR1 in EMC may be to deregulate the expression of specific genes involved
      in the tumoral process. In order to identify these genes, we have used a CFK2
      chondrogenic cell line over-expressing EWS/NOR1. A differential display analysis
      has identified the PLAGL1 gene as being down-regulated in the CFK2(EWS/NOR1) cell
      line compared to native CFK2 cells. RT-PCR analyses show that whereas the PLAGL1
      mRNAs encoding the two isoforms of the protein are highly expressed in four human
      chondrocyte immortalized cell lines and two human chondrocyte primary cultures,
      they are strongly down-regulated in six EMC tumors. We conclude that down
      regulation of PLAGL1 may be a significant contributing factor in the development
      of EMC tumors.

PMID- 16112422
TI  - Gemcitabine-mediated apoptosis is associated with increased CD95 surface
      expression but is not inhibited by DN-FADD in Colo357 pancreatic cancer cells.
AB  - This study investigates the role of caspase-8 and DN-FADD, an inhibitor of CD95
      dependent caspase-8 activation, in gemcitabine-induced apoptosis of Colo357
      pancreatic cancer cells. Gemcitabine-mediated apoptosis was monitored by the
      kinetics of caspase-8 activation and cytochrome c release. Gemcitabine treatment
      of Colo357 cells increased CD95 surface expression, raising the possibility of
      the involvement of CD95 in gemcitabine-mediated caspase-8 activation. However,
      ectopic expression of DN-FADD and treatment of cells with the antagonistic anti
      CD95 antibody ZB4 both failed to suppress gemcitabine-induced apoptosis but
      substantially inhibited CD95-mediated apoptosis. DN-FADD, which surprisingly
      accumulated in nuclei of Colo357 cells, was unable to block caspase-8 activation
      mediated by either gemcitabine or CD95. These observations argue against a role
      of CD95 in gemcitabine-induced caspase-8 activation and reveal that the anti
      apoptotic function of DN-FADD differs from caspase-8 inhibition in Colo357 cells.

PMID- 16112423
TI  - Associations of ErbB2, beta1-integrin and lipid rafts on Herceptin (Trastuzumab)
      resistant and sensitive tumor cell lines.
AB  - ErbB2-mediated transmembrane signaling is a key target of novel anticancer agents
      such as Herceptin. Our comparison of Herceptin resistant (JIMT-1, MKN-7) and
      sensitive (SKBR-3, N-87) cell lines demonstrates the importance of ErbB2
      association patterns involving integrins and lipid rafts. Flow cytometric FRET
      and confocal microscopic measurements revealed colocalization and molecular
      proximity between beta1-integrins and ErbB2, as well as their association with
      lipid rafts. A weak functional interaction between ErbB2 and beta1-integrin and
      the fact that ErbB2 did not co-patch with beta1-integrins upon crosslinking imply
      that ErbB2 and beta1-integrin define two distinct molecular association clusters
      from a functional point of view. Although Herceptin-sensitive cell lines
      expressed more ErbB2 and fewer beta1-integrin molecules on their surface than
      their resistant counterparts, this finding probably does not explain the
      Herceptin resistant phenotype due to the weak interaction between beta1-integrins
      and ErbB2. Our results imply that the true significance of the expression profile
      of proteins involved in oncogenesis can only be understood after characterizing
      their molecular interactions.

PMID- 16112424
TI  - Comparative gene and protein expression in primary cultures of epithelial cells
      from benign prostatic hyperplasia and prostate cancer.
AB  - Primary cultures are widely used to investigate the disease-specific biology of
      prostate cancer and benign prostatic hyperplasia (BPH). To identify genes
      differentially expressed between epithelial cells cultured from adenocarcinomas
      versus BPH tissues, we used probe array technology. Gene expression profiles were
      evaluated on Affymetrix Human Cancer G110 Array Chips containing approximately
      1900 cancer-related genes. After defined statistical analysis, genes that were
      over-expressed in cancer cultures were identified. Protein expression of four of
      the differentially expressed genes was measured in immunoblots, and the
      expression of two other genes was measured by real-time reverse transcription
      polymerase chain reaction (RT-PCR). While no gene or protein was consistently
      over-expressed in all cancer versus BPH cell cultures, cytokeratin 16 protein was
      highly elevated in several of the cancer cultures, suggesting that a
      hyperproliferative phenotype may be characteristic of prostate cancer cells.

PMID- 16112425
TI  - Comment on: Alves G, Menezes Trindade Macrini C, De Souza Nascimento P, Carlos
      Morais J, Augusto Ornellas A. Detection and expression of Epstein-Barr Virus
      (EBV) DNA in tissues from penile tumors in Brazil. Cancer Lett. 2004; 215(1):79
      82.

PMID- 16112426
TI  - Detection and expression of Epstein-Barr Virus (EBV) DNA in tissues from penile
      tumors in Brazil.

PMID- 16112427
TI  - Letter to the editor.

PMID- 16112428
TI  - Cytogenetic and molecular aspects of lung cancer.
AB  - Lung cancer is one of the most common cancers worldwide and its pathogenesis is
      closely associated with tobacco smoking. Continuous exposure of smoking
      carcinogens results in the accumulation of several alterations of tumorigenesis
      related genes leading to neoplastic bronchial lesions. Lung cancer is divided in
      two main histological groups, non-small cell lung carcinomas (NSCLCs) and small
      cell lung carcinomas (SCLCs). It seems that lung tumorigenesis is a multistep
      process in which a number of genetic events including alterations of oncogenes
      and tumor suppressor genes have been occurred. Cytogenetic abnormalities in lung
      cancer are very complex. However, a number of recurrent cytogenetic abnormalities
      have been identified. Many of these changes are common in both major histological
      groups of lung cancer while certain chromosomal abnormalities have been
      correlated with the stage or the grade of the tumors. In addition, several
      molecular alterations have been constantly found. Some of them are common in
      different histological subtypes of lung cancer and they appear to play an
      important role in the pathogenesis of lung cancer. A good understanding of the
      underlying genetic changes of lung tumorigenesis will provide new perspectives
      for early diagnosis and screening of high-risk individuals. In addition, a number
      of genetical prognostic factors have been identified as possibly helpful
      parameters in the evaluation of lung cancer patients. Further research is
      required in order to systematically investigate genetical alterations in lung
      cancer contributing to improvement of lung cancer classification and staging and
      to development of new molecular targeted therapies.

PMID- 16112430
TI  - The third-generation bisphosphonates inhibit proliferation of murine osteosarcoma
      cells with induction of apoptosis.
AB  - Third generation bisphosphonates (BPs), including YM175 and YM529, are known to
      inhibit bone resorption. The aim of this study was to evaluate the anti-tumor
      effects of these drugs on murine osteosarcoma cell lines, in terms of
      proliferation and apoptosis. We found that both YM175 and YM529 strongly
      inhibited the in vitro proliferation and induced apoptosis of murine osteosarcoma
      cells. YM529 was more effective than YM175 in inhibiting cell proliferation.
      These observations suggest that third-generation BPs directly affect on the
      proliferation and survival of osteosarcoma cells, which supports the possibility
      that they could be beneficial in the treatment of osteosarcoma patients.

PMID- 16112431
TI  - Immunohistochemical evaluation of heat shock proteins in normal and preinvasive
      lesions of the cervix.
AB  - Heat Shock Proteins (HSPs) are molecular chaperons with multiple functions
      relating to cellular homeostasis. Primary, HSPs are expressed in response to
      cellular stresses that may also include carcinogenesis. Patterns of expression
      have not been extensively evaluated in the multi-step carcinogenesis of cervical
      cancer (Normal --> HPV infection --> Cervical Precancer --> Cancer). We evaluated
      the expression of HSP40, HSP60, HSP70, and HSP90 in normal tissues (N=30), in
      cervical intraepithelial neoplasia grade 1 (CIN1)(synonymous with productive HPV
      infections) (N=32), and in CIN3 (cervical precancer)(N=25) by
      immunohistochemistry staining (graded 0-3) and compared the results to p16INK4a,
      a biomarker of oncogenic HPV infections and CIN3. We found strong patterns of
      increased HSP40, HSP60, and HSP70 immunostaining with increasing severity of the
      lesion in a manner similar to p16INK4a (P(Trend)<0.0005). No difference in
      staining intensity by grade of lesion was observed for HSP90 (P(Trend)=0.8).
      Tissue patterns in CIN3 of diffuse immunostaining for HSP40 and HSP70 were
      analogous to those observed for p16INK4a; HSP60 immunostaining appeared more
      punctate within cells than for other antigens although similar tissue patterns
      were observed. We conclude that HSP40, HSP60, and HSP70 expressions are up
      regulated in response to the development of CIN3 akin to p16INK4a expression.

PMID- 16112432
TI  - Electrochemical coagulation for textile effluent decolorization.
AB  - The three most commonly used dyestuffs in textile industry are reactive, acid,
      and dispersed dyes. One dye from each group, C.I. Reactive Blue-19, C.I. Acid Red
      266, and C.I. Disperse Yellow-218 was chosen to study the feasibility of
      coagulation for color removal. The dyes used in these experiments were chosen to
      represent the two major structural features: anthraquinone and azo dyes. Reactive
      Blue is an anthraquinone-based dye, and Acid Red and Disperse Yellow represent
      azo-based dyes. As there is no standard method to measure the color intensity, a
      Hach spectrophotometer was used to measure the absorbance before and after the
      dye solution was treated. Removal efficiencies on these dyes were obtained by
      measuring absorbance of a sample at 592 nm for Reactive Blue, 498 nm for Acid
      Red, and 428 nm for Disperse Yellow. Aluminum and ferric coagulants were produced
      in a parallel-plate electrochemical reactor by anodic dissolution. Removal
      efficiencies of more than 98%, in terms of absorbance, were observed in
      laboratory conditions. Removal was found highly dependent upon NaCl
      concentration, applied voltage, current density, and pH. The NaCl in the solution
      effectively reduced the power consumption and promoted the coagulant generation
      by depasivating the Al-water and Fe-water electrochemical systems. The processes
      were determined to be highly NaCl dependent. A mechanism was proposed for the
      corresponding liquid phase chemistry.

PMID- 16112434
TI  - Psychiatric evaluation of the dermatology patient.
AB  - Over one third of dermatologic disorders have significant psychiatric
      comorbidity. The impact of the skin disorder on quality of life, the role of
      psychosocial stressors, and use of substances should be assessed. Major
      depressive disorder is the most frequently encountered psychiatric disorder in
      dermatology and is often associated with suicide risk. Other psychiatric
      syndromes comorbid with dermatologic disorders include obsessive-compulsive
      disorder, social phobia, posttraumatic stress disorder associated with
      dissociation and conversion symptoms, body image pathologies, delusional
      disorder, and a wide range of personality disorders. This article reviews
      psychiatric guidelines that may be used to assess psychopathology in the
      dermatology patient.

PMID- 16112435
TI  - Psychosomatic factors in dermatology.
AB  - Psychosomatics describes any aspect of dermatology with psychologic or
      psychiatric elements. Dermatologists know that a significant proportion of their
      practice involves patients for whom psychologic elements either partially or
      sometimes entirely dominate their presenting chief complaints. This article
      explores the role of psychosomatic factors in dermatologic disorders. The authors
      discuss the clinical interface between psychiatry, psychology and dermatology and
      the interpretation of possible relationships between cutaneous diseases, the role
      of the mind, and psychotherapeutic interventions.

PMID- 16112436
TI  - Stress and psychoneuroimmunologic factors in dermatology.
AB  - There is clinical and experimental evidence that the brain can start, influence,
      and stop biologic skin events. Studies suggest that the skin, as a relevant part
      of the "diffuse brain," can modify the quality of perceptions and feelings. The
      immune and the endocrine systems seem to represent the protagonists of the
      modulation of those events and, in this context, psychosocial stressors and
      interventions can lead to global health changes of great interest for
      dermatologists.

PMID- 16112437
TI  - The emotional impact of chronic and disabling skin disease: a psychoanalytic
      perspective.
AB  - This article discusses some major early factors that influence the evolving
      psychologic development, which in turn helps determine the emotional impact that
      chronic or disabling skin disease may have on patients' lives. If the emotional
      environment, encompassed by the infant-caretaker relationship, is less than
      optimal, the stability of the body image may be compromised, self-esteem
      diminished, and affect less well handled and the somatic expression of emotional
      content may ensue. Each of these is important in dermatology, as is the nature of
      the disease and the capacity of families and of society to adapt. Psoriasis,
      atopic dermatitis, and acne are used as examples.

PMID- 16112438
TI  - Psychosomatic factors in dermatology: special perspectives for application in
      clinical practice.
AB  - The identification of psychosomatic factors in dermatology has always been one of
      the principal themes in the history of this field and in the personal experience
      and research of the author. After a brief review of some of the milestones in the
      area of psychosomatic factors in dermatology, the author presents the criteria
      dictated by clinical experience, in the absence to date of more precise
      scientific data, for the individuation of such psychosomatic factors in clinical
      practice.

PMID- 16112439
TI  - Stigma experience in skin disorders: an Indian perspective.
AB  - Dermatologic disorders generally have a major impact on patients' daily
      activities, psychologic and emotional state, and social relationships. The
      intensity of impact of skin disease on an individual person is extremely
      variable, however, and depends on natural history of the disorder; the patient's
      demographic characteristics, personality, character, and value; the patient's
      life situation; and the attitudes of society. Social stigma toward dermatologic
      disorders in the Indian society is quite widespread, especially toward leprosy.
      Dermatologists are expected to consider quality of life issues along with social
      aspects, nature of disorder, efficacy, and tolerability of various therapeutic
      options to optimize relief and comfort to their patient.

PMID- 16112440
TI  - Psychosocial aspects of aging skin.
AB  - Many older individuals use products and procedures to conceal or delay the signs
      of aging. For most, this provides a helpful ego boost, but some suffer from
      pathologies such as eating disorders and body dysmorphic disorder. The impact of
      aging skin may include social anxiety and social isolation. Poor self-image is
      associated with chronic illness and fewer preventive health behaviors, such as
      exercise. Aged appearance, especially in women, is also associated with workplace
      discrimination. Patients should therefore be offered treatments for aging skin,
      ensured that society's negative views not be unnecessarily reinforced, and
      maintain a realistic treatment expectations.

PMID- 16112441
TI  - Psychologic trauma, posttraumatic stress disorder, and dermatology.
AB  - Psychologic trauma refers to events (such as sexual assault, major earthquake, or
      plane crashes) that overwhelm an individual's capacity to cope. Psychologic
      trauma can result in chronic and recurring dermatologic symptoms that persist
      after the trauma subsides. Examples are cutaneous sensory flashbacks (which may
      be fragments of the sensory component of the traumatic experience), autonomic
      hyperarousal (with symptoms such as profuse sweating or flare-up of an underlying
      stress-reactive dermatosis), conversion symptoms (such as numbness, pain, or
      other medically unexplained cutaneous symptoms), and cutaneous self-injury
      (manifesting in many forms, including trichotillomania, dermatitis artefacta, and
      neurotic excoriations--tension-reducing behaviors in patients who have
      posttraumatic stress disorder).

PMID- 16112442
TI  - Depression and skin disease.
AB  - The occurrence of depression in association with dermatologic disease is common.
      Psychiatric disturbance is reported in approximately 30% of dermatology patients.
      Depression can have varied presentations and is more relevant clinically in
      dermatology patients during critical psychosocial periods of development. Early
      recognition and treatment of depression associated with skin disorders can lead
      to improved therapeutic outcomes and may avert disastrous outcomes, including
      suicide.

PMID- 16112443
TI  - Acne, depression, and suicide.
AB  - Acne is a common disorder that may have a considerable psychologic impact
      including anxiety and depression. Depression and suicide occur frequently in
      adolescents and young adults. Although case reports suggest an association
      between isotretinoin and depression and suicide, more rigorous observational
      studies and epidemiologic studies, using different designs, have not shown any
      effect of isotretinoin use in increasing the occurrence of depression and
      suicide. It is prudent for the practitioner to continue to use isotretinoin to
      treat severe acne, while at the same time informing patients and their relatives
      that depressive symptoms should be actively assessed at each visit and, if
      necessary, referral to a psychiatrist and a discontinuation of isotretinoin
      should be considered.

PMID- 16112444
TI  - Obsessive-compulsive disorders and dermatologic disease.
AB  - Obsessive-compulsive disorder and obsessive-compulsive spectrum disorders are
      often associated with dermatologic manifestations. The phenomenology is discussed
      and possible animal models explored. Treatment involves both pharmacotherapy and
      cognitive behavior therapy. Many of these patients experience considerable shame
      over their behavior and may be reluctant to acknowledge the existence of a
      psychiatric disorder. The dermatologist's approach to this patient is discussed.

PMID- 16112445
TI  - Psychologic factors in psoriasis: consequences, mechanisms, and interventions.
AB  - The article examines the English-language research literature concerning
      psychologic aspects of psoriasis published since 1995. The literature is
      concerned with (1) the consequences of psoriasis in terms of quality of life,
      disability, depression, anxiety, and stigmatization and factors that may predict
      such outcomes; (2) potential mechanisms of the interaction between psychologic
      factors, stress, and the pathophysiology of psoriasis; and (3) examination of the
      clinical utility of psychologic interventions on extent of psoriasis and
      psychologic distress. The implications of the findings are discussed with
      reference to future directions for research and practice.

PMID- 16112446
TI  - Psychoneuroimmunodermatology of atopic dermatitis: from empiric data to the
      evolutionary hypothesis.
AB  - Atopic dermatitis is a pruritic skin disease affecting predominantly young
      people. There is evidence that psychologic stress constitutes an increased risk
      for atopy and influences the disease's clinical course. This risk is believed
      mediated by the effects of stress on neuroimmunoregulation, which in turn
      modulates the hypersensitivity response and involves immunoglobulin E-mediated
      inflammation, helper T-cell 2 predominance, and eosinophilia. This article
      examines theoretic perspectives and other behavioral dimensions, such as maternal
      caring behavior, infant response to stress, temperament, and the so-called
      "hygiene hypothesis." The Darwinian framework and the mental scenario are
      examined. These processes may be akin to the generation of antibodies by the
      immune system.

PMID- 16112447
TI  - Evaluating clinical rating scales for evidence-based dermatology: some basic
      concepts.
AB  - Evidence-based dermatology has necessitated the development of rating scales that
      measure multidimensional and abstract constructs, such as quality of life. This
      article discusses some basic psychometric concepts, such as reliability,
      validity, standardization, and measurement precision, which need to be considered
      when choosing a clinical rating instrument. Also discussed is the impact of these
      parameters on increasing the statistical power of a clinical trial.

PMID- 16112448
TI  - A critical review of Quality-of-Life Scales for Psoriasis.
AB  - Psoriasis can have a major impact on the lives of patients who have psoriasis and
      many different methods are described to measure this effect. This article
      describes four general health measures, six dermatology-specific measures, four
      psoriasis-specific measures, and four utility measure concepts that are used in
      psoriasis. For each of these, the extent of validation, including reliability of
      each measure and correlation with other measures, is described. The experience of
      use of each measure is summarized and key references listed. Advice is given
      concerning strategy for choosing which measures to use.

PMID- 16112449
TI  - Massage therapy for skin conditions in young children.
AB  - Two studies are reviewed that highlight the positive effects of massage therapy
      on skin conditions in young children. In the first study children being treated
      on a burn trauma unit received 30-minute massages before debridement or dressing
      change. The children who received massage therapy were more relaxed during the
      procedure. In the study on children with eczema, those who were massaged during
      the application of their skin medication showed less anxiety after the massage
      sessions. Across the massage period the children also showed an improved clinical
      condition including less redness, lichenification, scaling, excoriation, and
      pruritus.

PMID- 16112450
TI  - Complementary psychocutaneous therapies in dermatology.
AB  - The skin and the nervous system develop side by side in the fetus and remain
      intimately interconnected and interactive throughout life. Because of the skin
      nervous system interactions, there is a significant psychosomatic or behavioral
      component to many dermatologic conditions. This permits complementary
      nonpharmacologic psychotherapeutic interventions, such as acupuncture,
      aromatherapy, biofeedback, cognitive-behavioral therapy, hypnosis, placebo, and
      suggestion, to have positive impacts on many dermatologic diseases. Complementary
      pharmacologic psychotherapeutic interventions, such as herbs and supplements,
      also may help improve some dermatologic disorders.

PMID- 16112452
TI  - Laser treatment of vascular lesions.
AB  - Lasers and other light sources have been developed that remove or improve many
      vascular lesions that were previously untreatable. Port-wine stains are the most
      notable example. Vascular lasers and light sources represent a major advance in
      dermatology for cosmetic and non-cosmetic applications. This article reviews the
      common vascular conditions amenable to laser therapy and the approaches and
      devices used.

PMID- 16112451
TI  - Psychopharmacologic therapies in dermatology: an update.
AB  - Many patients who have skin disorders have associated psychosocial issues.
      Psychotropic agents with improved side-effect profiles are available to allow
      physicians who are not psychiatrists to manage patients who have psychiatric
      conditions with agents that are effective, simple to administer, and generally
      well tolerated. Dermatologists who wish to help their patients who have
      psychodermatologic conditions can enhance their armamentarium by becoming
      familiar with the use of a few selected psychotropic agents. This article reviews
      the current status and future directions of psychopharmacology for the major
      types of psychopathologies encountered in dermatology practice.

PMID- 16112453
TI  - Medial septal/diagonal band cells express multiple functional nicotinic receptor
      subtypes that are correlated with firing frequency.
AB  - The medial septum-diagonal band (MS/DB) contains primarily cholinergic and
      GABAergic neurons that project to the hippocampus, and are important for learning
      and memory. Whole-cell patch clamp methods with brain slices from p11--p20 rats
      were used to measure MS/DB cell responses to focal somatic application of 1mM
      acetylcholine (ACh) and a series of current pulses was applied in order to assess
      firing frequencies and the presence of hyperpolarization-activated currents (Ih).
      We identified three types of cells: (1) cells with fast inward currents blocked
      by methyllycaconitine (MLA) with slow firing rates (3--12 Hz), accommodating
      action potentials, and no Ih (n=20); (2) cells with currents that had both fast
      (MLA-sensitive) and slow components that were blocked with mecamylamine (MEC)
      that showed fast firing (up to 60 Hz) and slow firing (up to 3 Hz), with
      accommodating and non-accommodating action potentials (n=46), 33% of which had
      Ih; and (3) cells not responsive to ACh with moderate firing rates (10--42 Hz),
      some with accommodating action potentials and some without (n=19), of which 92%
      had Ih. These results are among the first to demonstrate functional nicotinic
      receptors in the MS/DB. The data suggest that these receptors include alpha 7 and
      non-alpha 7 subtypes and that the expression of each is correlated with firing
      frequency and the presence of Ih. Responses to ACh were not affected by
      tetrodotoxin (TTX) and CdC l(2) but were blocked by MLA or MLA and MEC,
      suggesting that these currents involve direct activation of nicotinic receptors.

PMID- 16112454
TI  - Voltage-gated calcium channels are not involved in generation and propagation of
      spreading depression (SD) in the brainstem of immature rats.
AB  - Spreading depression (SD) can be elicited in the brainstem of rats younger than
      13 days when excitability is enhanced by acetate superfusion [F. Richter, S.
      Rupprecht, A. Lehmenkuhler, H.-G. Schaible, Spreading depression can be elicited
      in brain stem in immature but not adult rats, J. Neurophysiol. 90 (2003) 2163-
      2170]. To investigate whether voltage-gated calcium channels (VGCCs) modify
      initiation and propagation of SD in this type of tissue, we applied specific
      blockers to L-, T-, P/Q-, and N-type VGCCs locally or systemically. SD-related
      d.c. potentials and concomitant increases in extracellular potassium
      concentration ([K(+)](e)) were unaffected by the L- and T-type VGCC blocker
      flunarizine that was applied either systemically (up to 2mg/kg body weight) or by
      superfusion onto the brainstem (40 microM). In addition, local application of the
      P/Q-type VGCC blocker omega-agatoxin (1 microM) or of the N-type VGCC blocker
      omega-conotoxin (1 microM) to the brainstem surface did not influence SD. The
      results indicate that VGCCs do not modify the generation or propagation of SDs in
      the brainstem of the immature rat. Blockade of N-type VGCCs disturbed the normal
      breathing rhythm. Application of alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) (250-1000 microM) that elicited SD in the immature cortex,
      failed to elicit SD in the immature brainstem. In summary, it is likely that K(+)
      initiates and propagates brainstem SDs.

PMID- 16112455
TI  - Parallel changes in gene expression in aged human and mouse cortex.
AB  - The intensity of expression of over 20,000 genes and expressed sequence tags
      within the cerebral cortex has previously been described for both the human and
      mouse genomes. In both these species, the degree of expression of a relatively
      limited number of cortical genes, around 300, is significantly altered during
      senescence. The extent of similarity between age-related alterations of levels of
      specific mRNAs in either species has been compared. There is a significant
      correlation between species in those genes whose expression changes markedly in
      either direction with aging. This parallel serves to validate the use of mouse
      strains to study general age-related genetic events associated with aging.

PMID- 16112456
TI  - Propofol-mediated impairment of CA1 long-term potentiation in mouse hippocampal
      slices.
AB  - Propofol (2,6-diisopropylphenol) is a short-acting intravenous anesthetic.
      Propofol is known to impair maintenance of long-term potentiation (LTP) in
      synaptic responses from Schaffer collateral-commissural (SC) pathway to CA1
      pyramidal cells in the hippocampus, but the threshold concentration of propofol
      needed to elicit this action is unknown. The actions of propofol in vivo (e.g.,
      amnesia, sedation, hypnosis and immobility) depend on its concentration, and thus
      it is necessary to determine the concentration required to impair CA1 LTP in
      order to assess the impact of impairment in vivo. In the present study, we
      investigated the effects of various concentrations of propofol on synaptic
      plasticity, primarily by measuring LTP at SC pathway to CA1 pyramidal cell
      synapses in mouse hippocampal slices. Continuous application of 50 microM
      propofol from 20 min before tetanus stimulation suppressed potentiation of the
      synaptic responses by tetanus stimulation. The suppression was pronounced from 10
      min post-tetanus and about 55% suppression of the potentiation was observed at 60
      min after tetanus. Propofol at 5 or 20 microM did not have this effect. The
      presence of gamma-aminobutyric acid type A (GABA(A)) receptors antagonist,
      picrotoxin, abrogated the suppression of LTP by 50 microM propofol. Propofol 50
      microM did not affect long-term depression (LTD). These results suggest that the
      suppression of hippocampal CA1 LTP via GABA(A) receptors requires a much higher
      propofol concentration compared with that needed to induce amnesia.

PMID- 16112457
TI  - Melatonin treatment counteracts the hyperthermic effect of lipopolysaccharide
      injection in the Syrian hamster.
AB  - The present study examined the acute response in body temperature to
      lipopolysaccharide (LPS) injection to Syrian hamsters at two time intervals
      during the light-dark cycle. Its modification by melatonin (MT) administration in
      the drinking water was also assessed. Hamsters were intraperitoneally (i.p.)
      implanted with a transmitter to measure core body temperature. MT was
      administered from day 8 post-surgery until the end of experiment. On day 16 after
      surgery, LPS or saline was injected i.p. at the beginning of the light phase (ZT
      0) or of the scotophase (ZT 14). At ZT 0, LPS increased core body temperature, an
      effect that persisted for at least 5h and that was blunted by MT administration.
      At ZT 14, the hyperthermic effect of LPS was absent. Rather, at ZT 14 the animals
      showed increases in core body temperature following saline or LPS during the
      first 2h after injection only, which were significantly less intense in LPS
      treated animals. MT administration blunted this difference. Five days after
      injection, hamsters that had received LPS at ZT 0 showed an increase in the mesor
      of core body temperature rhythm as compared to saline. This effect was suppressed
      by MT administration. The results demonstrate that MT prevents body temperature
      increase after LPS at ZT 0.

PMID- 16112458
TI  - Neoechinorhynchus curemai (Acanthocephala: Neoechinorhynchidae) in Prochilodus
      lineatus (Osteichthyes: Prochilodontidae) from the Parana River, Brazil.
AB  - This work evaluated parasitic infections by Neoechinorhynchus curemai
      (Acanthocephala: Neoechinorhynchidae) in Prochilodus lineatus captured between
      August 2000 and August 2001 in the Parana River, Presidente Epitacio, Sao Paulo,
      Brazil. Of 87 fishes examined, 59 were infected (25 males and 34 females). High
      mean intensities occurred in August 2000 (45.2, range 2-204), September 2000
      (28.5, range 11-73), October 2000 (59.3, range 2-250) and February 2001 (27.3,
      range 3-73). There was no relationship of rainfall with mean intensity and
      prevalence. Males were more parasitized (P<0.05) than females. This work
      contributes to the knowledge of helminth parasites of fish from a little studied
      region of the Parana River, showing diversity in their fauna when compared to
      other places in the same river.

PMID- 16112459
TI  - Purification, characterization, cDNA cloning, and expression of asialofetuin
      binding C-type lectin from eggs of shishamo smelt (Osmerus [Spirinchus]
      lanceolatus).
AB  - A novel C-type lectin (OLABL) was isolated from the eggs of shishamo smelt
      [Osmerus (Spirinchus) lanceolatus] by affinity chromatography on asialofetuin
      Sepharose. OLABL had a molecular mass of 29 kDa on SDS-PAGE under nonreducing
      conditions and two subunits with masses of 15 kDa (OLABL-H) and 14 kDa (OLABL-L)
      under reducing conditions. Thus, OLABL is a heterodimeric protein. cDNA sequence
      analysis revealed that the H- and L-subunits of OLABL were composed of 137 and
      136 amino acid residues, respectively, and showed almost identical (95%)
      sequences, with slight differences in the N-terminal and C-terminal regions.
      Since each subunit contained only the characteristic motif of C-type lectin-like
      domain (CTLD), EPN-E-WND, OLABL is a member of group VII of the CTLD-containing
      protein family. Although OLABL had an EPN sequence that is known as a mannose
      specific motif found in the collectin family, OLABL agglutinated rabbit
      erythrocytes without the addition of Ca(2+) ion, and this activity was inhibited
      by l-rhamnose and d-galactose derivatives, but not by d-mannose and d-glucose.
      These results indicate that OLABL has similar characteristics to AJL-2, a calcium
      independent lactose specific lectin isolated from Japanese eel skin mucus.
      Recombinant OLABLs (rHisOLABLs), His-tagged homodimers of the H- and L-subunits,
      were refolded from inclusion bodies expressed by Escherichia coli. rHisOLABL-L
      was recovered as a soluble form, but rHisOLABL-H was hardly dissolved in a
      renaturing buffer. The specific activities of rHisOLABL-L, rHisOLABL-H, and
      native OLABL were 500, 36, and 20, respectively. These findings suggest that the
      combination of subunits may affect the solubility and activity of these dimeric
      form lectins.

PMID- 16112461
TI  - Mutant KRAS, chromosomal instability and prognosis in colorectal cancer.
AB  - The RAS gene family provides a global effect on gene expression by encoding small
      GTP-binding proteins which act as molecular switches connecting extracellular
      signals with nuclear transcription factors. While wild type RAS proteins are
      switched off shortly after activation, mutant RAS proteins remain constitutively
      activated leading to complex interactions among their downstream effectors. For
      some human tumor types, these interactions were shown to contribute to cancer
      genesis and progression by inducing changes in cell survival, apoptosis,
      angiogenesis, invasion and metastasis. This review addresses the controversial
      link of KRAS mutations in colorectal cancer with chromosomal instability and
      patient prognosis.

PMID- 16112460
TI  - Oxidative inactivation of paraoxonase--implications in diabetes mellitus and
      atherosclerosis.
AB  - Human serum paraoxonase (PON1) has been implicated to play an important role in
      cardiovascular disease and diabetes. Studies in the literature indicate that PON1
      has two different enzyme activities, i.e., esterase and hydroperoxide reducing
      activities. The objective of this study was to establish the importance of these
      two activities and to distinguish between them. As the addition of copper
      immediately inactivated the enzyme, we used auto-oxidation as the model system.
      Auto-oxidation of HDL resulted in more than 80% reduction of the esterolytic
      activity, which was protected by antioxidants, Vitamin E (50%) and PDTC (95%) and
      completely by 1 M glucose. In contrast, the hydroperoxide reducing activity,
      using unesterified hydroperoxides remained unaffected with time. We also used
      pNPHPODE (novel substrate) to establish that hydrolysis might be a prerequisite
      for the enzyme to act on the esterified hydroperoxide. The results indicated that
      the hydrolysis of the substrate was inhibited under oxidizing conditions with no
      reduction of the hydroperoxide. Overall, our findings suggest that protecting the
      esterolytic activity of PON1 by antioxidants might be important in preserving its
      action on phospholipid peroxides and a concerted reaction involving the
      esterolytic and hydroperoxide reducing activities might be suggested for the
      action of PON1.

PMID- 16112462
TI  - Matching IMRT fields with static photon field in the treatment of head-and-neck
      cancer.
AB  - Radiation treatment with intensity-modulated radiation therapy (IMRT) for head
      and-neck cancer usually involves treating the superior aspects of the target
      volume with intensity-modulated (IM) fields, and the inferior portion of the
      target volume (the low neck nodes) with a static anterior-posterior field
      (commonly known as the low anterior neck, or LAN field). A match line between the
      IM and the LAN fields is created with possibly large dose inhomogeneities, which
      are clinically undesirable. We propose a practical method to properly match these
      fields with minimal dependence on patient setup errors. The method requires mono
      isocentric setup of the IM and LAN fields with half-beam blocks as defined by the
      asymmetric jaws. The inferior jaws of the IM fields, which extend approximately 1
      cm inferiorly past the isocenter, are changed manually before patient treatment,
      so that they match the superior jaw of the LAN field at the isocenter. The
      matching of these fields therefore does not depend on the particular treatment
      plan of IMRT and depends only on the matching of the asymmetric jaws.
      Measurements in solid water phantom were performed to verify the field-matching
      technique. Dose inhomogeneities of less than 5% were obtained in the match-line
      region. Feathering of the match line is done twice during the course of a
      treatment by changing the matching jaw positions superiorly at 3-mm increments
      each time, which further reduces the dose inhomogeneity. Compared to the method
      of including the lower neck nodes in the IMRT fields, the field-matching
      technique increases the delivery efficiency and significantly reduces the total
      treatment time.

PMID- 16112463
TI  - Measurement of dosimetric parameters for the Alpha-Omega high-dose-rate Iridium
      192 source.
AB  - Thermoluminescent (TLD) measurements of dose-rate constant, anisotropy function,
      and radial dose function are reported for the Alpha-Omega high dose rate (HDR)
      Iridium-192 ((192)Ir) source, which has been available since 1998 for use in the
      MicroSelectron HDR afterloader manufactured by the Nucletron Corporation.
      Measurement results are compared with published or available Monte Carlo
      calculations for both sources. They are found in good agreement, and, within
      experimental accuracy, no difference is seen in the dosimetric parameters of both
      sources.

PMID- 16112464
TI  - Fluorescent screen for high-dose-rate (HDR) brachytherapy quality assurance.
AB  - This article describes apparatus for quickly checking the positioning and dwell
      times of a high-dose-rate (HDR) afterloader as part of daily quality assurance
      (QA). A groove was milled into an aluminum plate to align an HDR applicator, and
      fluorescent screens were placed on either side of the groove. Lines were drawn at
      the fluorescent screen corresponding to distances to which the radioactive source
      should travel in our daily QA treatment protocol. By dimming the room lights, the
      fluorescence from the source was seen with a closed-circuit video camera, and the
      positioning accuracy and dwell time of the source could be efficiently verified.
      Not only is this an excellent QA tool, but it also provides good training for
      radiation therapists and other HDR professionals.

PMID- 16112465
TI  - Determination of CT-to-density conversion relationship for image-based treatment
      planning systems.
AB  - The implementation of tissue inhomogeneity correction in image-based treatment
      planning will improve the accuracy of radiation dose calculations for patients
      undergoing external-beam radiotherapy. Before the tissue inhomogeneity correction
      can be applied, the relationship between the computed tomography (CT) value and
      density must be established. This tissue characterization relationship allows the
      conversion of CT value in each voxel of the CT images into density for use in the
      dose calculations. This paper describes the proper procedure of establishing the
      CT value to density conversion relationship. A tissue characterization phantom
      with 17 inserts made of different materials was scanned using a GE Lightspeed
      Plus CT scanner (120 kVp). These images were then downloaded into the Eclipse and
      Pinnacle treatment planning systems. At the treatment planning workstation, the
      axial images were retrieved to determine the CT value of the inserts. A region of
      interest was drawn on the central portion of the insert and the mean CT value and
      its standard deviation were determined. The mean CT value was plotted against the
      density of the tissue inserts and fitted with bilinear equations. A new set of CT
      values vs. densities was generated from the bilinear equations and then entered
      into the treatment planning systems. The need to obtain CT values through the
      treatment planning system is very clear. The 2 treatment planning systems use
      different CT value ranges, one from -1024 to 3071 and the other from 0 to 4096.
      If the range is correct, it would result in inappropriate use of the conversion
      curve. In addition to the difference in the range of CT values, one treatment
      planning system uses physical density, while the other uses relative electron
      density.

PMID- 16112466
TI  - Inverse vs. forward breast IMRT planning.
AB  - Breast intensity-modulated radiation therapy (IMRT) improves dose distribution
      homogeneity within the whole breast. Previous publications report the use of
      inverse or forward dose optimization algorithms. Because the inverse technique is
      not widely available in commercial treatment planning systems, it is important to
      compare the 2 algorithms. The goal of this work is to compare them on a
      prospective cohort of 30 patients. Dose distributions were evaluated on
      differential dose-volume histograms using the volumes receiving more than 105%
      (V(105)) and 110% (V(110)) of the prescribed dose, and on the maximum dose
      (D(max)) or hot spot and the sagittal dose gradient (SDG) being the gradient
      between the dose on inframammary crease and the dose prescribed. The data were
      analyzed using Wilcoxon signed rank test. The inverse planning significantly
      improves the V(105) (mean value 9.7% vs. 14.5%, p=0.002), and the V(110) (mean
      value 1.4% vs. 3.2%, p=0.006). However, the SDG is not statistically
      significantly different for either algorithm. Looking at the potential impact on
      skin acute reaction, although there is a significant reduction of V(110) using an
      inverse algorithm, it is unlikely this 1.6% volume reduction will present a
      significant clinical advantage over a forward algorithm. Both algorithms are
      equivalent in removing the hot spots on the inframammary fold, where acute skin
      reactions occur more frequently using a conventional wedge technique. Based on
      these results, we recommend that both forward and inverse algorithms should be
      considered for breast IMRT planning.

PMID- 16112467
TI  - A review of prostate motion with considerations for the treatment of prostate
      cancer.
AB  - The motion of the prostate gland can influence the efficacy of radiation therapy.
      This article examines the literature concerning prostate gland motion with
      considerations for the treatment of cancer. The objectives of this review include
      providing radiation oncologists, medical physicists, and dosimetrists with data
      to assist in determining the best treatment adaptation for individual patients.
      The prostate gland is not a static structure, but rather a dynamic structure and
      this should be a consideration in the treatment protocol. The treatment planning
      personnel must add a margin to the clinical treatment volume (CTV) radiation
      field to account for prostate motion and patient setup errors resulting in a
      planning treatment volume (PTV). The movement of the prostate in a radiation
      field with a small margin to protect the anterior rectum may allow the posterior
      aspect of the gland to escape the prescribed dose. Thus, an understanding of
      potential prostate movements in radiation therapy is critical to achieve tumor
      control and minimize radiation complications in patients.

PMID- 16112468
TI  - Total scalp irradiation using helical tomotherapy.
AB  - Homogeneous irradiation of the scalp poses technical and dosimetric challenges
      due to the extensive, superficial, curved treatment volume. Conventional
      treatments on a linear accelerator use multiple matched electron fields or a
      combination of electron and photon fields. Problems with these techniques include
      dose heterogeneity in the target due to varying source-to-skin distance (SSD) and
      angle of beam incidence, significant dose to the brain, and the potential for
      overdose or underdose at match lines between the fields. Linac-based intensity
      modulated radiation therapy (IMRT) plans have similar problems. This work
      presents treatment plans for total scalp irradiation on a helical tomotherapy
      machine. Helical tomotherapy is well-suited for scalp irradiation because it has
      the ability to deliver beamlets that are tangential to the scalp at all points.
      Helical tomotherapy also avoids problems associated with field matching and use
      of more than one modality. Tomotherapy treatment plans were generated and are
      compared to plans for treatment of the same patient on a linac. The resulting
      tomotherapy plans show more homogeneous target dose and improved critical
      structure dose when compared to state-of-the-art linac techniques. Target
      equivalent uniform dose (EUD) for the best tomotherapy plan was slightly higher
      than for the linac plan, while the volume of brain tissue receiving over 30 Gy
      was reduced by two thirds. Furthermore, the tomotherapy plan can be more reliably
      delivered than linac treatments, because the patient is aligned prior to each
      treatment based on megavoltage computed tomography (MVCT).

PMID- 16112469
TI  - A case study of radiotherapy planning for a bilateral metal hip prosthesis
      prostate cancer patient.
AB  - The purpose of this report is to communicate the observed advantage of intensity
      modulated radiotherapy (IMRT) in a patient with bilateral metallic hip
      prostheses. In this patient with early-stage low-risk disease, a dose of 74 Gy
      was planned in two phases--an initial 50 Gy to the prostate and seminal vesicles
      and an additional 24 Gy to the prostate alone. Each coplanar beam avoided the
      prosthesis in the beam's eye view. Using the same target expansions for each
      phase, IMRT and 3D-conformal radiotherapy (CRT) plans were compared for target
      coverage and inhomogeneity as well as dose to the bladder and rectum. The results
      of the analysis demonstrated that IMRT provided superior target coverage with
      reduced dose to normal tissues for both individual phases of the treatment plan
      as well as for the composite treatment plan. The dose to the rectum was
      significantly reduced with the IMRT technique, with a composite V 80 of 35% for
      the IMRT plan versus 70% for 3D-CRT plan. Similarly, the dose to the bladder was
      significantly reduced with a V 80 of 9% versus 20%. Overall, various dosimetric
      parameters revealed the corresponding 3D-CRT plan would not have been acceptable.
      The results indicate significant success with IMRT in a clinical scenario where
      there were no curative alternatives for local treatment other than external beam
      radiotherapy. Therefore, definitive external beam radiation of prostate cancer
      patients with bilateral prosthesis is made feasible with IMRT. The work described
      herein may also have applicability to other groups of patients, such as those
      with gynecological or other pelvic malignancies.

PMID- 16112470
TI  - Potential role of inducible nitric oxide synthase in the sleep-wake states
      occurrence in old rats.
AB  - Extensive evidences now suggest that an association between inducible nitric
      oxide synthase and oxidative stress takes place during aging. Since the part
      played by inducible nitric oxide synthase in the sleep impairments associated
      with aging still remains unexplored, we compared its involvement in old rats (20
      24 months) versus adult ones (3-5 months) using polygraphic, biochemical,
      voltammetric and immunohistochemical techniques. The experiments were conducted
      either in basal condition or after a systemic injection of selected inducible
      nitric oxide synthase inhibitors. We found that 2-amino-5,6-dihydro-6-methyl-4H
      1,3-thiazine (10 mg/kg, i.p.) or aminoguanidine (400 mg/kg, i.p.) was capable to
      suppress rapid-eye-movement sleep and induce a delayed enhancement in slow-wave
      sleep in old rats. These effects did not occur in adult animals. Within the
      frontal cortex, the laterodorsal tegmentum and dorsal raphe nuclei, the basal
      inducible nitric oxide synthase activity was 85-200% higher in old rats than in
      adult ones. In contrast, the neuronal nitric oxide synthase activity did not vary
      in both groups. 2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine administration
      significantly reduced inducible nitric oxide synthase activity (70-80% according
      to the brain areas) independently of age, but significantly decreased the
      cortical nitric oxide release in old rats. Finally, in frontal cortex and dorsal
      raphe immunohistochemical analysis showed inducible nitric oxide synthase
      positive cells again only in old animals. These data support the idea that nitric
      oxide produced by inducible nitric oxide synthase plays a role in the triggering
      and maintenance of rapid-eye-movement sleep during aging.

PMID- 16112472
TI  - Caloric restriction prevents aging-associated changes in spike-mediated Ca2+
      accumulation and the slow afterhyperpolarization in hippocampal CA1 pyramidal
      neurons.
AB  - In hippocampal pyramidal neurons from aged animals voltage-gated Ca2+ entry and
      the slow, post-burst afterhyperpolarization are enhanced. As a result, there is a
      decrease in neuronal excitability and, in turn, an alteration in synaptic
      plasticity. Restricting the caloric intake of a rodent is a well-known paradigm
      for increasing lifespan and ameliorating a number of neurodegenerative features
      of aging, including deficits in synaptic plasticity and cognition. Here we show
      in rat CA1 pyramidal neurons from aged animals (18-20 months old) that a
      restricted diet prevents the enhancement of dendritic spike-mediated Ca2+
      accumulation. In contrast, no significant changes in the rates of Ca2+ recovery
      were observed suggesting that Ca2+ clearance mechanisms are not affected by aging
      or caloric restriction. Lastly, we found that caloric restriction also prevented
      the aging-associated increase in the slow, post-burst afterhyperpolarization. Our
      results suggest that caloric restriction-sensitive changes in Ca2+ accumulation
      and membrane excitability may in part account for the protective effects of
      dietary restriction on synaptic plasticity and learning deficits in aged animals.

PMID- 16112471
TI  - Electrophysiological properties and thermosensitivity of mouse preoptic and
      anterior hypothalamic neurons in culture.
AB  - Responses of mouse preoptic and anterior hypothalamic neurons to variations of
      temperature are key elements in regulating the setpoint of homeotherms. The goal
      of the present work was to assess the relevance of culture preparations for
      investigating the cellular mechanisms underlying thermosensitivity in
      hypothalamic cells. Our working hypothesis was that some of the main properties
      of preoptic/anterior hypothalamic neurons in culture are similar to those
      reported by other authors in slice preparations. Indeed, cultured
      preoptic/anterior hypothalamic neurons share many of the physiological and
      morphological properties of neurons in hypothalamic slices. They display
      heterogenous dendritic arbors and somatic shapes. Most of them are GABAergic and
      their activity is synaptically driven by the activation of alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid/kainate receptors. Active membrane properties
      include a depolarizing "sag" in response to hyperpolarization, and a low
      threshold spike, which is present in a majority of cells and is generated by T
      type Ca2+ channels. In a fraction of the cells, the low threshold spike repeats
      rhythmically, either spontaneously, or in response to depolarization. The
      background synaptic noise in cultured neurons is characterized by the presence of
      numerous postsynaptic potentials which can be easily distinguished from the
      baseline, thus providing an opportunity for assessing their possible roles in
      thermosensitivity. An unexpected finding was that GABA-A receptors can generate
      both hyper- and depolarizing postsynaptic potentials in the same neuron. About
      20% of the spontaneously firing preoptic/anterior hypothalamic neurons are warm
      sensitive. Warming (32-41 degrees C) depolarizes some cells, a phenomenon which
      is Na+-dependent and tetrodotoxin-insensitive. The increased firing rate of warm
      sensitive cells in response to warming can be prepotential and/or synaptically
      driven. Overall, our data suggest that a warm-sensitive phenotype is already
      developed in cultured cells. Therefore, and despite obvious differences in their
      networks, cultured and slice preparations of hypothalamic neurons can complement
      each other for further studies of warm-sensitivity at the cellular and molecular
      level.

PMID- 16112473
TI  - Sex-specific effects of chronic anabolic androgenic steroid treatment on GABA(A)
      receptor expression and function in adolescent mice.
AB  - Anabolic androgenic steroids are synthetic derivatives of testosterone designed
      for therapeutic uses, but now taken as drugs of abuse. Potential health risks
      associated with anabolic androgenic steroid abuse are believed to be higher in
      adolescents than in adults, but few studies have tested anabolic androgenic
      steroid effects in adolescent subjects or determined if effects of these steroids
      differ between females and males. We have studied GABA(A) receptor expression and
      function in the medial preoptic nucleus of mice chronically treated during
      adolescence with the anabolic androgenic steroid, 17alpha-methyltestosterone.
      Three-week treatment did not elicit significant differences the expression of
      alpha1, alpha2 or alpha5 subunit mRNAs in animals of either sex, although there
      was a trend toward decreases in all three subunit mRNAs in female mice, which was
      augmented and attained significance for the alpha2 subunit mRNA in females
      treated for six weeks. Immunocytochemical analysis revealed that treatment with
      17alpha-methyltestosterone for 6 weeks also elicited a significant decrease in
      the number of alpha2-immunopositive neurons in female subjects. To test if
      anabolic androgenic steroid treatment also promoted changes in GABA(A) receptor
      function, spontaneous inhibitory synaptic currents were analyzed in adolescent
      animals treated for 3-4 weeks. This treatment regimen promoted a significant
      decrease in spontaneous inhibitory synaptic current frequency in female, but not
      male mice. Finally, anabolic androgenic steroid treatment was found to have no
      effect on the numbers of interneurons within the medial preoptic nucleus, as
      assessed by immunoreactivity for calcium binding proteins, suggesting that the
      decrease in the frequency of spontaneous inhibitory synaptic currents in female
      mice does not arise from an anabolic androgenic steroid-induced loss of
      interneurons. Taken together, our results indicate that chronic exposure to
      17alpha-methyltestosterone elicits significant changes in GABAergic transmission
      in the medial preoptic nucleus of female, but not male, mice effectively
      enhancing the sexually dimorphic nature of GABAergic transmission in a forebrain
      region crucial for the expression of aggression and sexual behaviors.

PMID- 16112475
TI  - Localization of alpha-synuclein to identified fibers and synapses in the normal
      mouse brain.
AB  - Alpha-synuclein is a synaptic associated protein that is found throughout the
      brain. Although its function is not fully understood, various roles have been
      proposed, including the mobilization of synaptic vesicles and plasticity.
      However, interest in this molecule is mainly focused on its role in
      neurodegenerative diseases such as Parkinson's disease, where it is a major
      component in cellular inclusions. Although it is widely accepted that alpha
      synuclein is distributed to terminals and fibers throughout the brain, the
      identity of the pathways that contain this protein is not known. To address this
      issue, we combined immunocytochemistry with anterograde tract-tracing in mouse to
      identify the projections that are alpha-synuclein immunopositive. We find that it
      is present in corticostriatal, nigrostriatal and striatonigral terminals. Our
      data support the concept that alpha-synuclein is normally present in at least
      some of the terminals of inclusion-forming neurons, but that it is also present
      in the axonal boutons of neurons that do not apparently accumulate this protein
      pathologically.

PMID- 16112474
TI  - Preference for cocaine- versus pup-associated cues differentially activates
      neurons expressing either Fos or cocaine- and amphetamine-regulated transcript in
      lactating, maternal rodents.
AB  - We studied the neuronal basis of the motivational response to two powerful but
      radically different rewards-cocaine and maternal nurturing of pups in the
      postpartum rat (dam) which is in a unique motivational state. We used a place
      preference method designed to offer a choice between cues associated with a
      natural reinforcer (pups) and those associated with a pharmacologic reinforcer
      (cocaine). Using c-Fos or cocaine- and amphetamine-regulated transcript (CART)
      immunocytochemistry, we identified the neuronal groups that are activated when
      the dams expressed a preference for either cues-associated with pups or cues
      associated with cocaine. Dams that preferred the cocaine-associated cues had more
      c-Fos positive neurons in medial prefrontal cortex, nucleus accumbens, and
      basolateral nucleus of amygdala than pup-associated cue preferring dams or
      control. Except for the accumbens, there was activation of neurons in these same
      regions with the pup-associated cue preference. In the nucleus accumbens only
      CART-immunoreactive (not c-Fos) neurons were activated with pup-cue preference.
      Notably, the medial preoptic area was the single area where greater activation of
      neurons was seen with a preference for pup-associated versus cocaine-associated
      cues. These responses were identified in the absence of the stimuli (cocaine or
      pups) and are proposed to be, in part, activation of these neurons related to
      motivational processing. Neither the distribution of neurons responding to pup
      associated cue preference nor the demonstration that CART-expressing neurons are
      responsive to reward-associated cue preference has been previously reported. We
      hypothesize that the expression of preference for cocaine versus pup-associated
      cues is made possible by the concerted activity of these regionally distributed
      networks of neurons that are in part specific to the preference response.

PMID- 16112476
TI  - Physiological control of emotion-related behaviors by endogenous enkephalins
      involves essentially the delta opioid receptors.
AB  - The endogenous pentapeptide enkephalins bind to the mu and delta opioid
      receptors, with a slightly higher affinity for the latter. It remains a
      controversy regarding the respective physiological role of mu and delta opioid
      receptors in the control of emotion and motivation. One of the difficulties to
      investigate this problem is the low tonic extracellular release of enkephalins in
      various brain structures. To overcome this problem the synaptic levels of these
      pentapeptides were enhanced by inhibition of enzymes involved in their catabolism
      with the selective inhibitor H3N-CH(CH2-CH2-S-CH3)-CH2-S-S-CH2-CH(CH2phi)-CONH
      CH(CH2phi)-COOCH2phi (RB101). This compound was shown to increase the
      extracellular levels and lifetime of endogenous enkephalins. Similar responses
      were obtained in wild-type and mu opioid receptor knockout mice following RB 101
      administration in behavioral tests measuring locomotor activity, anxiety
      (elevated O-maze), and motivation (forced swim test and conditioned suppression
      of motility). In contrast, RB 101 led to antinociceptive responses only in wild
      type animals using hot plate and tail immersion tests. These results clearly
      demonstrate the critical role of delta opioid receptors activated by the
      endogenous opioid peptides, in the physiological control of emotion- and
      motivation-related behaviors. In contrast, antinociceptive modulation, at least
      with respect to thermal nociceptive stimuli, involves enkephalin-activated mu
      opioid receptors. These findings could open new perspectives in the treatment of
      mood disorders using either inhibitors of enkephalin catabolism or delta opioid
      agonists.

PMID- 16112477
TI  - Disruption of ephrin-A/EphA binding alters synaptogenesis and neural connectivity
      in the hippocampus.
AB  - Ephrins are guidance cues that modulate axonal growth and the subsequent axonal
      topographic maps in many regions of the CNS. Here we studied the functional roles
      of ephrin-A/EphA interactions in the layer-specific pattern of axonal projections
      in the hippocampus by disrupting the ephrin-A signaling by over-expression of a
      soluble EphA receptor. Tracing experiments in EphA5-Fc over-expressing mice
      revealed that reduction of ephrin-A/EphA interactions did not affect the proper
      distribution of the main hippocampal afferents, i.e. entorhinal and commissural
      projections. However, further ultrastructural analyses showed a reduction in the
      density of synaptic terminals in the entorhinal and commissural termination
      layers in these mice. In addition, using anti-calbindin antibodies, we analyzed
      the dentate mossy fiber projections following disruption of ephrin-A/EphA
      interactions throughout developing hippocampus. While the main mossy fiber bundle
      appeared normal, the infrapyramidal bundle formed longer projections that
      established ectopic contacts in these transgenic mice. Later, the expected
      specific pruning of the infrapyramidal bundle was not observed at adult stages.
      Ultrastructural analyses confirmed a higher number of mossy fiber terminals in
      the infrapyramidal bundle in adult EphA5-Fc transgenic mice and showed that these
      terminals were larger and established a greater number of contacts than in
      controls. Our results demonstrate that ephrin-A/EphA interactions regulate the
      synaptogenesis of hippocampal afferents and the proper development and refinement
      of granule cell projections.

PMID- 16112478
TI  - Central serotonin 3 receptors play an important role in the modulation of
      nociceptive neural activity of trigeminal subnucleus caudalis and nocifensive
      orofacial behavior in rats with persistent temporomandibular joint inflammation.
AB  - The role of central serotonin 3 receptors on neural activities recorded from
      superficial laminae of trigeminal subnucleus caudalis/upper cervical spinal cord
      junction region was investigated using rats with (Complete Freund's Adjuvant day
      7 group) or without (non-Complete Freund's Adjuvant group) persistent
      temporomandibular joint inflammation evoked by Complete Freund's Adjuvant for 7
      days. We identified two types of units, Deep-wide dynamic range units and Skin
      wide dynamic range units from extracellular recordings. Deep-wide dynamic range
      units have mechanoreceptive fields in the deep craniofacial tissues including
      masseter muscle but do not have cutaneous mechanoreceptive fields. Deep-wide
      dynamic range unit discharges evoked by the formalin injection into masseter
      muscle were significantly enhanced in the late phase in Complete Freund's
      Adjuvant day 7 group. Discharges of Skin-wide dynamic range units evoked by the
      noxious pinch stimulation to facial skin in Complete Freund's Adjuvant day 7
      group were significantly enhanced compared with those in non-Complete Freund's
      Adjuvant group. Topical administration of central serotonin 3 receptor
      antagonist, tropisetron, onto trigeminal subnucleus caudalis/upper cervical
      spinal cord junction region significantly reduced both formalin-evoked Deep-wide
      dynamic range unit and pinch-evoked Skin-wide dynamic range unit discharges in
      non-Complete Freund's Adjuvant and Complete Freund's Adjuvant day 7 groups
      significantly. The inhibitory effects of tropisetron on pinch-evoked Skin-wide
      dynamic range unit discharges were prolonged in Complete Freund's Adjuvant day 7
      group compared with those in non-Complete Freund's Adjuvant group. The role of
      central serotonin 3 receptors in trigeminal subnucleus caudalis/upper cervical
      spinal cord junction region was also tested by orofacial formalin test in
      Complete Freund's Adjuvant day 7 group. Intracisternal administration of
      tropisetron decreased the orofacial nocifensive behavior in the late phase evoked
      by the injection of formalin into the masseter muscle. These results suggest that
      central serotonin 3 receptors in trigeminal subnucleus caudalis/upper cervical
      spinal cord junction region are involved in mediating pronociceptive effects in
      both superficial and deep craniofacial tissues nociception during persistent
      temporomandibular joint inflammation.

PMID- 16112479
TI  - Effects of N-methyl-D-aspartate glutamate receptor antagonists on oscillatory
      signal propagation in the guinea-pig accessory olfactory bulb slice:
      characterization by optical, field potential and patch clamp recordings.
AB  - To characterize the role of N-methyl-d-aspartate glutamate receptors in
      oscillations induced by a single electrical stimulation of the vomeronasal nerve
      layer, optical, field potential and patch clamp recordings were carried out in
      guinea-pig accessory olfactory bulb slice preparations. Bath application of the N
      methyl-D-aspartate receptor antagonists, 2-amino-5-phosphonovaleric acid or MK
      801, produced an increase in frequency of oscillating waves (oscillation) in
      external plexiform and mitral cell layers. The removal of Mg2+ from perfusate
      abolished oscillations, while subsequent application of 2-amino-5
      phosphonovaleric acid or MK-801 restored oscillations. Vomeronasal nerve layer
      evoked postsynaptic currents were analyzed by whole-cell clamp recordings from
      mitral and granule cells. A long-lasting excitatory postsynaptic current and
      periodic inhibitory postsynaptic currents, which were superimposed on the long
      excitatory postsynaptic current, were observed in mitral cells. The frequency of
      the periodic inhibitory postsynaptic currents correlated with the frequency of
      oscillations observed in the optical and field potential recordings. Furthermore,
      periodic inhibitory postsynaptic currents were blocked by puff application of
      bicuculline to the external plexiform layer/mitral cell layer, where mitral cells
      make dendrodendritic synapses with granule cells. In addition, puff application
      of the non-N-methyl-D-aspartate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione,
      to the external plexiform layer/mitral cell layer suppressed an early phase of
      periodic inhibitory postsynaptic currents (membrane oscillation), whereas 2-amino
      5-phosphonovaleric acid suppressed the late phase of periodic inhibitory
      postsynaptic currents. These data indicate that periodic excitatory postsynaptic
      currents of granule cells induce relevantly periodic inhibitory postsynaptic
      currents in mitral cells via dendrodendritic synapses and suggest that feedback
      inhibition regulates generation of oscillation via activation of non-N-methyl-d
      aspartate glutamate receptors and gradual attenuation of oscillation via
      activation of N-methyl-D-aspartate receptors on granule cells.

PMID- 16112480
TI  - Glutamic acid decarboxylase and GABA immunoreactivities in the cerebellar cortex
      of adult rat after prenatal exposure to a low concentration of carbon monoxide.
AB  - Glutamic acid decarboxylase and GABA immunoreactivities were qualitatively and
      quantitatively evaluated in the cerebellar cortex of adult rats prenatally
      exposed to a low concentration of carbon monoxide (75 parts per million). Carbon
      monoxide-exposed and control rats were perfused with modified Bouin's fluid and
      their cerebella were embedded in paraffin. Sections from the vermis of each
      cerebellum were stained with Toluidine Blue or assayed with anti-glutamic acid
      decarboxylase 65/67 or with anti-GABA antisera. In the Toluidine Blue-stained
      sections, no differences were observed in the microscopic structure of the
      cerebellar cortex between carbon monoxide-exposed rats and controls. The
      distribution patterns of glutamic acid decarboxylase and GABA immunoreactivities
      in the cerebellar cortex of the treated animals were qualitatively comparable to
      those of the controls, and in accordance with previous descriptions of glutamic
      acid decarboxylase and GABA immunoreactivities in the rat cerebellar cortex.
      However, quantitative analyses demonstrated a significant reduction of
      immunoreactivities to both substances in the exposed rats in comparison with the
      controls. The reduction regarded: in the molecular layer, the number of glutamic
      acid decarboxylase/GABA-immunoreactive neuronal bodies and of axon terminals and
      the area they covered; in the Purkinje neuron layer, the number and the area
      covered by glutamic acid decarboxylase/GABA immunoreactive axon terminals. The
      differences detected in the prenatally exposed adult rats could be due to carbon
      monoxide-induced impairment of the differentiation of cerebellar GABA
      synthesizing neurons. A consequently diminished synthesis of GABA might account
      for some behavioral disorders detected in adult rats submitted to the same
      experimental procedure.

PMID- 16112481
TI  - Effects of perinatal asphyxia on cell proliferation and neuronal phenotype
      evaluated with organotypic hippocampal cultures.
AB  - The present report summarizes studies combining an in vivo and in vitro approach,
      where asphyxia is induced in vivo at delivery time of Wistar rats, and the long
      term effects on hippocampus neurocircuitry are investigated in vitro with
      organotypic cultures plated at postnatal day seven. The cultures preserved
      hippocampus layering and regional subdivisions shown in vivo, and only few dying
      cells were observed when assayed with a viability test at day in vitro 27. When
      properly fixed, cultures from asphyxia-exposed animals showed a decreased amount
      of microtubule-associated protein-2 immunocytochemically positive cells
      (approximately 30%), as compared with that from controls. The decrease in
      microtubule-associated protein-2 immunocytochemistry was particularly prominent
      in Ammon's horn 1 and dentate gyrus regions (approximately 40%). 5-Bromo
      2'deoxyuridine labeling revealed a two-fold increase in cellular proliferation in
      cultures from asphyxia-exposed, compared with that from control animals.
      Furthermore, confocal microscopy and quantification using the optical disector
      technique demonstrated that in cultures from asphyxia-exposed animals
      approximately 30% of 5-bromo-2'deoxyuridine-positive cells were also positive to
      microtubule-associated protein-2, a marker for neuronal phenotype. That
      proportion was approximately 20% in cultures from control animals. Glial
      fibrillary acidic protein-immunocytochemistry and Fast Red nuclear staining
      revealed that the core of the hippocampus culture was surrounded by a well
      developed network of glial fibrillary acidic protein-positive cells and glial
      fibrillary acidic protein-processes providing an apparent protective shield
      around the hippocampus. That shield was less developed in cultures from asphyxia
      exposed animals. The increased mitotic activity observed in this study suggests a
      compensatory mechanism for the long-term impairment induced by perinatal
      asphyxia, although it is not clear yet if that mechanism leads to neurogenesis,
      astrogliogenesis, or to further apoptosis.

PMID- 16112483
TI  - Coordinated development of leading biomass pretreatment technologies.
AB  - For the first time, a single source of cellulosic biomass was pretreated by
      leading technologies using identical analytical methods to provide comparative
      performance data. In particular, ammonia explosion, aqueous ammonia recycle,
      controlled pH, dilute acid, flowthrough, and lime approaches were applied to
      prepare corn stover for subsequent biological conversion to sugars through a
      Biomass Refining Consortium for Applied Fundamentals and Innovation (CAFI) among
      Auburn University, Dartmouth College, Michigan State University, the National
      Renewable Energy Laboratory, Purdue University, and Texas A&M University. An
      Agricultural and Industrial Advisory Board provided guidance to the project.
      Pretreatment conditions were selected based on the extensive experience of the
      team with each of the technologies, and the resulting fluid and solid streams
      were characterized using standard methods. The data were used to close material
      balances, and energy balances were estimated for all processes. The
      digestibilities of the solids by a controlled supply of cellulase enzyme and the
      fermentability of the liquids were also assessed and used to guide selection of
      optimum pretreatment conditions. Economic assessments were applied based on the
      performance data to estimate each pretreatment cost on a consistent basis.
      Through this approach, comparative data were developed on sugar recovery from
      hemicellulose and cellulose by the combined pretreatment and enzymatic hydrolysis
      operations when applied to corn stover. This paper introduces the project and
      summarizes the shared methods for papers reporting results of this research in
      this special edition of Bioresource Technology.

PMID- 16112484
TI  - Combined sugar yields for dilute sulfuric acid pretreatment of corn stover
      followed by enzymatic hydrolysis of the remaining solids.
AB  - A number of previous studies determined dilute acid pretreatment conditions that
      maximize xylose yields from pretreatment or glucose yields from subsequent
      digestion of the pretreated cellulose, but our emphasis was on identifying
      conditions to realize the highest yields of both sugars from both stages. Thus,
      individual xylose and glucose yields are reported as a percentage of the total
      potential yield of both sugars over a range of sulfuric acid concentrations of
      0.22%, 0.49% and 0.98% w/w at 140, 160, 180 and 200 degrees C. Up to 15% of the
      total potential sugar in the substrate could be released as glucose during
      pretreatment and between 15% and 90+% of the xylose remaining in the solid
      residue could be recovered in subsequent enzymatic hydrolysis, depending on the
      enzyme loading. Glucose yields increased from as high as 56% of total maximum
      potential glucose plus xylose for just enzymatic digestion to 60% when glucose
      released in pretreatment was included. Xylose yields similarly increased from as
      high as 34% of total potential sugars for pretreatment alone to between 35% and
      37% when credit was taken for xylose released in digestion. Yields were shown to
      be much lower if no acid was used. Conditions that maximized individual sugar
      yields were often not the same as those that maximized total sugar yields,
      demonstrating the importance of clearly defining pretreatment goals when
      optimizing the process. Overall, up to about 92.5% of the total sugars originally
      available in the corn stover used could be recovered for coupled dilute acid
      pretreatment and enzymatic hydrolysis. These results also suggest that enhanced
      hemicellulase activity could further improve xylose yields, particularly for low
      cellulase loadings.

PMID- 16112482
TI  - Neuron specific alpha-adrenergic receptor expression in human cerebellum:
      implications for emerging cerebellar roles in neurologic disease.
AB  - Recent data suggest novel functional roles for cerebellar involvement in a number
      of neurologic diseases. Function of cerebellar neurons is known to be modulated
      by norepinephrine and adrenergic receptors. The distribution of adrenergic
      receptor subtypes has been described in experimental animals, but corroboration
      of such studies in the human cerebellum, necessary for drug treatment, is still
      lacking. In the present work we studied cell-specific localizations of alpha1
      adrenergic receptor subtype mRNA (alpha 1a, alpha 1b, alpha 1d), and alpha2
      adrenergic receptor subtype mRNA (alpha 2a, alpha 2b, alpha 2c) by in situ
      hybridization on cryostat sections of human cerebellum (cortical layers and
      dentate nucleus). We observed unique neuron-specific alpha1 adrenergic receptor
      and alpha2 adrenergic receptor subtype distribution in human cerebellum. The
      cerebellar cortex expresses mRNA encoding all six alpha adrenergic receptor
      subtypes, whereas dentate nucleus neurons express all subtype mRNAs, except alpha
      2a adrenergic receptor mRNA. All Purkinje cells label strongly for alpha 2a and
      alpha 2b adrenergic receptor mRNA. Additionally, Purkinje cells of the anterior
      lobe vermis (lobules I to V) and uvula/tonsil (lobules IX/HIX) express alpha 1a
      and alpha 2c subtypes, and Purkinje cells in the ansiform lobule (lobule HVII)
      and uvula/tonsil express alpha 1b and alpha 2c adrenergic receptor subtypes.
      Basket cells show a strong signal for alpha 1a, moderate signal for alpha 2a and
      light label for alpha 2b adrenergic receptor mRNA. In stellate cells, besides a
      strong label of alpha 2a adrenergic receptor mRNA in all and moderate label of
      alpha 2b message in select stellate cells, the inner stellate cells are also
      moderately positive for alpha 1b adrenergic receptor mRNA. Granule and Golgi
      cells express high levels of alpha 2a and alpha 2b adrenergic receptor mRNAs.
      These data contribute new information regarding specific location of adrenergic
      receptor subtypes in human cerebellar neurons. We discuss our observations in
      terms of possible modulatory roles of adrenergic receptor subtypes in cerebellar
      neurons responding to sensory and autonomic input signals, and review species
      differences in cerebellar adrenergic receptor expression.

PMID- 16112485
TI  - Partial flow of compressed-hot water through corn stover to enhance hemicellulose
      sugar recovery and enzymatic digestibility of cellulose.
AB  - Flowthrough pretreatment with compressed-hot water can significantly increase the
      removal of xylan and lignin and enhance xylose sugar yields and cellulose
      digestibility, especially at high flow rates. However, continuous flowthrough
      operations that realize these benefits suffer from a large amount of water
      consumption that leads to high energy requirements for pretreatment and
      downstream processing. Because high flow rates are particularly effective early
      in hemicellulose hydrolysis and less effective later, flow with compressed-hot
      water was applied at selected intervals, and performance was compared with that
      of batch and flowthrough operations for corn stover pretreated with compressed
      hot water at 200 degrees C. Partial flow reduced water consumption by 60%
      compared with continuous flowthrough operation but still achieved higher xylose
      sugar yields (84-89%) compared to batch pretreatment (46.6%). In addition, corn
      stover cellulose pretreated by partial flow had higher enzymatic digestibility
      (88-90%) than batch operations (approximately 85%) at otherwise identical
      conditions, apparently due to much higher lignin removal for the former (40-45%
      vs 10-12%). Partial flow also reduced degradation, with recovery of xylose and
      glucose in the solids and hydrolyzate increased to 90-92% vs only about 76% for
      batch operation. The partial flow approach could be further improved by
      optimizing the operating strategy and reaction conditions, suggesting that this
      novel pretreatment could lead to advanced biomass pretreatment technology.

PMID- 16112486
TI  - Optimization of pH controlled liquid hot water pretreatment of corn stover.
AB  - Controlled pH, liquid hot water pretreatment of corn stover has been optimized
      for enzyme digestibility with respect to processing temperature and time. This
      processing technology does not require the addition of chemicals such as sulfuric
      acid, lime, or ammonia that add cost to the process because these chemicals must
      be neutralized or recovered in addition to the significant expense of the
      chemicals themselves. Second, an optimized controlled pH, liquid hot water
      pretreatment process maximizes the solubilization of the hemicellulose fraction
      as liquid soluble oligosaccharides while minimizing the formation of monomeric
      sugars. The optimized conditions for controlled pH, liquid hot water pretreatment
      of a 16% slurry of corn stover in water was found to be 190 degrees C for 15 min.
      At the optimal conditions, 90% of the cellulose was hydrolyzed to glucose by
      15FPU of cellulase per gram of glucan. When the resulting pretreated slurry, in
      undiluted form, was hydrolyzed by 11FPU of cellulase per gram of glucan, a
      hydrolyzate containing 32.5 g/L glucose and 18 g/L xylose was formed. Both the
      xylose and the glucose in this undiluted hydrolyzate were shown to be fermented
      by recombinant yeast 424A(LNH-ST) to ethanol at 88% of theoretical yield.

PMID- 16112487
TI  - Lime pretreatment and enzymatic hydrolysis of corn stover.
AB  - Corn stover was pretreated with an excess of calcium hydroxide (0.5 g Ca(OH)2/g
      raw biomass) in non-oxidative and oxidative conditions at 25, 35, 45, and 55
      degrees C. The optimal condition is 55 degrees C for 4 weeks with aeration.
      Glucan (91.3%) and xylan (51.8%) were converted to glucose and xylose
      respectively, when the treated corn stover was enzymatically hydrolyzed with 15
      FPU/g cellulose. Only 0.073 g Ca(OH)2 was consumed per g of raw corn stover. Of
      the initial lignin, 87.5% was maximally removed. Almost all acetyl groups were
      removed. After 4 weeks at 55 degrees C with aeration, some cellulose and
      hemicellulose were solubilized as monomers and oligomers in the pretreatment
      liquor. When considering the dissolved fragments of glucan and xylan in the
      pretreatment liquor, the overall yields of glucose and xylose were 93.2% and
      79.5% at 15 FPU/g cellulose. The pretreatment liquor has no inhibitory effect on
      ethanol fermentation.

PMID- 16112488
TI  - Pretreatment and fractionation of corn stover by ammonia recycle percolation
      process.
AB  - Corn stover was pretreated with aqueous ammonia in a flow-through column reactor,
      a process termed as Ammonia Recycle Percolation (ARP). The aqueous ammonia causes
      swelling and efficient delignification of biomass at high temperatures. The ARP
      process solubilizes about half of xylan, but retains more than 92% of the
      cellulose content. Enzymatic digestibility of ARP-treated corn stover is 93% with
      10 FPU/g-glucan enzyme loading. The SEM pictures and FTIR spectra confirm
      swelling and delignification effects of the ARP process. The X-ray
      crystallography data indicate that the basic crystalline structure of the
      cellulosic component of corn stover is not altered by the ARP treatment. Low
      liquid ARP can reduce the liquid throughput and residence time to 3.3 mL/g
      biomass and 10-12 min, without adversely affecting the overall effectiveness. The
      low-water ARP achieved 73.4% delignification and 88.5% digestibility with 15
      FPU/g-glucan. The ethanol yield from the SSF of low-liquid ARP-treated corn
      stover using Saccharomyces cerevisiae reached 84% of the theoretical maximum.
      Successive operation of a hot-water treatment and the ARP was applied as a method
      of biomass fractionation. The two-stage process separated xylan in the first
      stage (84%) and lignin in the second stage (75%), resulting treated solid that
      contains 79% glucan.

PMID- 16112489
TI  - Optimization of the ammonia fiber explosion (AFEX) treatment parameters for
      enzymatic hydrolysis of corn stover.

PMID- 16112490
TI  - Process and economic analysis of pretreatment technologies.
AB  - Five pretreatment processes (dilute acid, hot water, ammonia fiber explosion
      (AFEX), ammonia recycle percolation (ARP), and lime) for the liberation of sugars
      from corn stover are compared on a consistent basis. Each pretreatment process
      model was embedded in a full bioethanol facility model so that systematic effects
      for variations in pretreatment were accounted in the overall process. Economic
      drivers influenced by pretreatment are yield of both five and six carbon sugars,
      solids concentration, enzyme loading and hemicellulase activity. All of the
      designs considered were projected to be capital intensive. Low cost pretreatment
      reactors in some pretreatment processes are often counterbalanced by higher costs
      associated with pretreatment catalyst recovery or higher costs for ethanol
      product recovery. The result is little differentiation between the projected
      economic performances of the pretreatment options. Additional process performance
      data, especially involving the identification of optimal enzyme blends for each
      pretreatment approach and conditioning requirements of hydrolyzates at process
      relevant sugar concentrations resulting from each pretreatment may lead to
      greater differentiation in projected process economics.

PMID- 16112491
TI  - Comparative sugar recovery data from laboratory scale application of leading
      pretreatment technologies to corn stover.
AB  - Biological processing of cellulosic biomass to fuels and chemicals would open up
      major new agricultural markets and provide powerful societal benefits, but
      pretreatment operations essential to economically viable yields have a major
      impact on costs and performance of the entire system. However, little comparative
      data is available on promising pretreatments. To aid in selecting appropriate
      systems, leading pretreatments based on ammonia explosion, aqueous ammonia
      recycle, controlled pH, dilute acid, flowthrough, and lime were evaluated in a
      coordinated laboratory program using a single source of corn stover, the same
      cellulase enzyme, shared analytical methods, and common data interpretation
      approaches to make meaningful comparisons possible for the first time. Each
      pretreatment made it possible to subsequently achieve high yields of glucose from
      cellulose by cellulase enzymes, and the cellulase formulations used were
      effective in solubilizing residual xylan left in the solids after each
      pretreatment. Thus, overall sugar yields from hemicellulose and cellulose in the
      coupled pretreatment and enzymatic hydrolysis operations were high for all of the
      pretreatments with corn stover. In addition, high-pH methods were found to offer
      promise in reducing cellulase use provided hemicellulase activity can be
      enhanced. However, the substantial differences in sugar release patterns in the
      pretreatment and enzymatic hydrolysis operations have important implications for
      the choice of process, enzymes, and fermentative organisms.

PMID- 16112492
TI  - Prenatal androgen blockade accelerates pubertal development in male rhesus
      monkeys.
AB  - Aspects of the prenatal environment, including steroid hormones, modulate the
      timing of puberty onset in many mammalian species. This study tested whether
      prenatal androgen manipulations altered pubertal development in male rhesus
      macaques (Macaca mulatta). Pregnant females received testosterone enanthate (TE),
      the androgen receptor blocker flutamide, or vehicle during one of two periods of
      gestation, and their male offspring were observed for morphological, endocrine,
      and behavioral development from 3 to 4.5 years of age. Males exposed to flutamide
      early in gestation had a greater response to exogenous GnRH prepubertally, and
      greater testes volume, elevated testosterone, and elevated LH at age 3.5 than did
      control subjects. Males exposed to flutamide late in gestation also had greater
      testes volumes at age 3.5 than did control males. However, these differences
      between flutamide treated males and control males did not persist postpubertally.
      By 4.5 years of age, development in control males had reached comparable levels
      to that of flutamide-treated males. Late gestation treatment with TE had no
      effect on morphological pubertal development but early TE treatment altered some
      aspects of endocrine function during puberty. None of the prenatal androgen
      manipulations affected sexual behavior. These findings suggest that prenatal
      androgens, in conjunction with social factors, masculinize pubertal timing in
      rhesus monkey males.

PMID- 16112493
TI  - MAO A knockout attenuates adrenocortical response to various kinds of stress.
AB  - The effect of a lack of the gene encoding monoamine oxidase A (MAO A) in
      transgenic Tg 8 mice on the corticosterone response to restraint, cold, water
      deprivation-induced, or social acute stress as well as chronic variable stress
      was studied. It was found that Tg 8 mice with genetic MAO A knockout and wild
      type C3H/HeJ (C3H) strain showed similar plasma corticosterone resting level. MAO
      A knockout mice differed from C3H mice by attenuated response to restraint (60
      min), cold (4 degrees C, 60 min), and water deprivation (48 h) as well as to a
      chronic (15 days) variable stress. No difference between Tg 8 and C3H strains in
      the response to psychosocial stress (encounters for 30 min of six previously
      isolated mice) has been found. ACTH administration to dexamethasone-pretreated
      mice produced a similar corticosterone effect in Tg 8 and C3H mice, indicating
      that the decreased stress response in MAO A-deficient mice was due rather to the
      central mechanisms regulating stress-induced ACTH release than to adrenocortical
      responsiveness to ACTH.

PMID- 16112494
TI  - Disorders of eating behavior: correlation between hypothalamo-pituitary-thyroid
      function and psychopathological aspects.
AB  - Altered pituitary-thyroid (PT) function (TSH, FT4, FT3 plasma levels) was
      correlated with symptoms of Eating Disorders (ED) in 137 patients (65 ANR, 12
      ANP, 19 ANBP, 26 BN, 8 EDNOS-AN, 7 EDNOS-BN) and 30 controls. PT hormone
      concentrations were assessed by immunofluorimetry and psychopathology by EDI-2
      and HSCL-90. Values of TSH were decreased in ANP, BN, EDNOS-AN, of T4 in ANR,
      ANP, AN-BP, of T3 in ANR, ANP, ANBP, BN, EDNOS-AN, EDNOS-BN. TSH values
      correlated negatively with ineffectiveness in BN and EDNOS-AN, and with
      depression in EDNOS-AN. FT4 values correlated positively with perfectionism in
      ANR, ANP and ANBP, with interoceptive awareness in EDNOS-AN, and negatively with
      depression in EDNOS-AN and with body dissatisfaction in EDNOS-BN. FT3 values
      correlated positively with perfectionism in ANBP and BN, with ineffectiveness in
      ANR and ANP, with depression in EDNOS-AN, with hostility in ANR and EDNOS-BN,
      with interpersonal sensibility in ANP, with somatization in EDNOS-BN, and
      negatively with interpersonal distrust in EDNOS-AN. Prospective studies are
      needed to confirm whether or not altered PT parameters correlate with ED symptoms
      during the course of the diseases.

PMID- 16112495
TI  - Distribution of androgen receptor CAG repeat polymorphism in Chinese
      schizophrenia and its correlation with age at onset.
AB  - The action of androgens is mediated by the androgen receptors (ARs), which are
      located throughout the brain. The AR gene is implicated in the pathogenesis of
      schizophrenia because male siblings with schizophrenia share alleles at this gene
      at a rate higher than chance predicts, and differences in sex hormone function
      may explain the gender difference in schizophrenic manifestations. Since the
      shorter alleles of the AR CAG repeat polymorphism are associated with increased
      gene expression, we tested the hypothesis that the AR CAG repeat variant confers
      susceptibility to schizophrenia using a sample of 225 people with schizophrenia
      and 247 normal controls. Using the median AR repeat length in the normal group as
      the arbitrary cut-off point (<24 and >25 CAG repeats), the results show no
      association between the AR repeat length and schizophrenia in either sex.
      Furthermore. AR CAG repeat length did not affect the age of symptom onset in the
      schizophrenic population. Our findings suggest that it is unlikely that the AR
      CAG repeat polymorphism plays a major role in the pathogenesis of schizophrenia.
      Nevertheless, given that androgens affect cognitive function, violent behavior
      and mood, the effect of the AR CAG polymorphism on the clinical manifestations of
      schizophrenia may warrant further exploration.

PMID- 16112496
TI  - Rosmarinic acid content and RAPD analysis of in vitro regenerated basil (Ocimum
      americanum) plants.
AB  - Various in vitro cultures were established from shoot tips of Ocimum americanum
      seedlings. Rosmarinic acid content of the in vitro produced plants as well as
      parent plant were determined by HPLC analysis and subjected to RAPD analysis. MS
      medium with BA at a concentration of 1 mg/l and 0.25 mg/l IAA supports maximum
      rosmarinic acid production in plants produced from cultures grown on that medium.
      RAPD analysis revealed 64 scorable bands from four primers, including six
      polymorphic bands. The band pattern revealed differences between the parent plant
      and the in vitro regenerated plants. Certain band changes were found in O.
      americanum plants regenerated in vitro, suggesting the existence of genetic
      variation that might affect the biochemical synthesis of plants derived from
      tissue culture.

PMID- 16112497
TI  - Antibacterial effects of Coscinium fenestratum.
AB  - Antibacterial activity of Coscinium fenestratum is mainly due to the presence of
      berberine.

PMID- 16112498
TI  - A multicenter, double-blind, safety study of QR-333 for the treatment of
      symptomatic diabetic peripheral neuropathy. A preliminary report.
AB  - BACKGROUND: QR-333, a topical compound that contains quercetin, a flavonoid with
      aldose reductase inhibitor effects, ascorbyl palmitate, and vitamin D(3), was
      formulated to decrease the oxidative stress that contributes to peripheral
      diabetic neuropathy and thus alleviate its symptoms. This proof-of-principle
      study assessed the efficacy and safety of QR-333 against placebo in a small
      cohort of patients with diabetic neuropathy. METHODS: This randomized, placebo
      controlled, double-blind trial included 34 men and women (21-71 years of age)
      with Type 1 or 2 diabetes and diabetic neuropathy who applied QR-333 or placebo
      (2:1 ratio), three times daily for 4 weeks, to each foot where symptoms were
      experienced. Five-point scales were used to determine changes from baseline to
      endpoint in symptoms and quality of life (efficacy). Safety was assessed through
      concomitant medications, adverse events, laboratory evaluations, and physical
      examinations. RESULTS: QR-333 reduced the severity of numbness, jolting pain, and
      irritation from baseline values. Improvements were also seen in overall and
      specific quality-of-life measures. QR-333 was well tolerated. Eleven patients in
      the QR-333 group reported 23 adverse events (all mild or moderate); 4 in the
      placebo group reported 5 events (all moderate). One patient who applied QR-333
      noted a pricking sensation twice, the only adverse event considered possibly
      related to study treatment. CONCLUSIONS: From this preliminary safety study, it
      appears that QR-333 may safely offer relief of symptoms of diabetic neuropathy
      and improve quality of life. These findings warrant further investigation of this
      topical compound.

PMID- 16112499
TI  - The clinical characteristics of latent autoimmune diabetes in adults and its
      relation with chronic complications in metabolically poor controlled Turkish
      patients with Type 2 diabetes mellitus.
AB  - It has been reported that some patients with Type 2 diabetes mellitus (DM) have
      latent autoimmune diabetes in adults (LADA) and may show different clinical
      characteristics than those with Type 2 DM. We aimed to determine the ratio and
      clinical features of LADA in patients with diagnosed initially as Type 2 DM. We
      measured glutamic acid decarboxylase antibodies (GADA) in 54 patients, diagnosed
      clinically with Type 2 DM. Of 54 patients, 17 (31%) were GADA positive. GADA
      positive patients had significantly earlier diabetes onset age (P<.001), lower
      BMI (P<.05), and lower serum C-peptide value (P<.001) than did those who were
      GADA negative. A higher proportion of the GADA-positive patients were receiving
      insulin therapy (P<.01). With respect to the duration of DM, familial history of
      DM, and the levels of blood pressures, fasting plasma glucose, and HbA1c, there
      was no difference between the two groups. Nephropathy and retinopathy were more
      frequent in GADA-positive than in GADA-negative patients. The prevalence of
      neuropathy was comparable between the two groups. GADA was negatively associated
      with BMI, C-peptide levels, and diabetes-onset age, but positively related to
      retinopathy, nephropathy, and insulin treatment. This study indicated that the
      important portion of the patients who were initially diagnosed as Type 2 DM may
      have LADA. In Type 2 diabetic patients who have lower BMI and diagnosis of
      diabetes in relatively younger age, the possibility of LADA should be taken into
      consideration. The higher prevalence of nephropathy and retinopathy in GADA
      positive patients also suggests the importance of early diagnosis and strict
      metabolic control in these patients.

PMID- 16112500
TI  - Community-acquired infections in type 2 diabetic patients and their nondiabetic
      partners. The Fremantle Diabetes Study.
AB  - AIMS: The aim of this study was to investigate the association between Type 2
      diabetes and community-acquired infections. METHODS: We recruited 68 patients
      (mean+/-S.D. age=64.9+/-9.1 years; 57.4% males) from a community-based cohort and
      their nondiabetic partners (age=63.8+/-9.9 years; mean relationship
      duration=37.3+/-11.5 years) to a prospective observational matched-pair cohort
      study. Participants were assessed for infection risk factors and were required to
      complete an infection diary over the following year. RESULTS: Sixty patient
      partner pairs returned completed diaries. A greater proportion of patients than
      partners had received influenza vaccination in the past year (73.3% vs. 60.0%;
      P=.057), but pneumococcal vaccination coverage in the previous 5 years was
      similar (11.7% vs. 10.0%; P=1.0). The proportions of patients and partners
      reporting no infections were similar (51.7% vs. 58.3%; P=.52), but the diabetic
      patients were more likely to have experienced more than one infection (33.3% vs.
      18.3%: P=.022). Baseline glycosylated hemoglobin levels in patients with and
      without at least one infection were similar, and there was no association between
      multiple infections and glycosylated hemoglobin (P>.2 in each case). After
      adjusting for age and gender, the probability of at least one infection during
      follow-up was not associated with diabetes (P=.33), but the number of infections
      was positively associated with diabetes (P=.005). CONCLUSION/INTERPRETATION:
      Although similar proportions of Type 2 diabetic patients and their nondiabetic
      partners remained infection-free over a 12-month period, the diabetic patients
      who developed infections had a greater number of episodes. Glycemic control did
      not predict the risk or frequency of community-acquired infections in the
      diabetic group.

PMID- 16112501
TI  - The treadmill exercise-tolerance test is useful for the prediction and prevention
      of ischemic coronary events in elderly diabetics.
AB  - BACKGROUND: Approximately 80% of cases of ischemic heart disease (IHD) occur in
      patients with nonstenotic coronary arteries, and few studies have systematically
      assessed exercise testing (TMT) as a predictor of risk in the elderly. METHODS:
      TMT was carried out using a protocol for the independent and active elderly
      (n=176). After 4.1+/-0.5 years follow-up, logistic regression analysis was
      performed for each coronary risk factor such as diabetes mellitus (DM) and
      hypercholesterolemia (HC). According to the results, patients were divided into
      Gp HC, hypercholesterolemic patients; Gp DM, diabetics; Gp HC+DM,
      hypercholesterolemic diabetics; and Gp C, nonhyperlipidemic and nondiabetics.
      Sensitivity and specificity of TMT for IHD (significant stenosis or acute
      coronary syndrome) were analyzed. RESULTS: Odds ratios for each risk factors are
      as follows: DM, 4.167; HC, 4.485; and DM+HC, 8.652. Notably, TMT was 17.59. Age
      was a significant risk, but hypertension was not. Positive ischemic signs in TMT
      were observed in 52.7%, 28.6%, 33.3%, and 16.3% in the Gp HC+DM, HC, DM, and C
      groups, respectively. Only three participants complained of chest pain during the
      TMT. Significant stenosis was observed in 75.0%, 71.4%, 69.2%, and 60.0% of
      coronary angiography (CAG)-receiving patients of Gp HC, DM, HC+DM, and C. During
      the observation term, acute coronary syndromes occurred in 4.7%, 3.3%, 5.5%, and
      0% of patients in the Gp HC, DM, HC+DM, and C groups, respectively. The
      sensitivity of TMT for IHD was higher than 66.7% and specificity was higher than
      94.1% in each group. CONCLUSION: An exercise tolerance test in the elderly,
      especially for diabetics and hypercholesterolemic patients, is useful for the
      diagnosis of IHD.

PMID- 16112502
TI  - Small low-density lipoprotein and small low-density lipoprotein/total low-density
      lipoprotein are closely associated with intima-media thickness of the carotid
      artery in Type 2 diabetic patients.
AB  - BACKGROUND: The intima-media thickness (IMT) of the carotid artery, as determined
      by ultrasonography, is useful for reflecting the extent of subclinical
      atherosclerosis. We investigated the relationship between IMT and the serum
      concentrations of small low-density lipoprotein (LDL) in diabetic patients.
      METHODS: The study was conducted with 27 Type 2 diabetic patients (14 males and
      13 females; mean age=62.6+/-8.3 years) and 12 age-matched healthy controls. The
      LDL subfraction was measured using a polyacrylamide gel electrophoresis method.
      Vascular endothelial growth factor (VEGF) and platelet-derived growth factor
      (PDGF) concentrations were measured by an enzyme immunoassay. The IMT was
      expressed as the maximum IMT (Max-IMT) and average IMT (Ave-IMT) of the carotid
      artery, measured by ultrasonography. RESULTS: Both the IMT and the small LDL
      concentrations were significantly increased in the diabetic patients compared
      with the healthy participants. The IMTs were significantly correlated with small
      LDL concentration and small LDL/total LDL more than LDL concentrations by
      multivariate analysis. The IMTs were not significantly correlated with the serum
      VEGF or PDGF concentrations. The patients with a larger IMT had a significantly
      higher prevalence of hypertension or ischemic heart disease than did the patients
      with a normal IMT. CONCLUSIONS: The increased small LDL concentrations and small
      LDL/total LDL, in addition to total LDL concentrations, in Type 2 diabetic
      patients are closely associated with increased IMT of the carotid artery.

PMID- 16112503
TI  - Change in cutaneous perfusion following 10 weeks of aerobic training in Type 2
      diabetes.
AB  - A small, but positive, association between aerobic training status or prior
      maximal exercise and enhanced dorsal foot skin perfusion in active individuals
      with Type 2 diabetes has been shown. This study, therefore, was designed to
      examine whether an aerobic training intervention would positively affect
      cutaneous perfusion in sedentary Type 2 diabetic individuals as well. Nine
      sedentary participants with Type 2 diabetes (DS) and 10 obese nondiabetic
      controls (CS) were studied. Prior to the initiation of aerobic training, dorsal
      foot cutaneous perfusion was measured noninvasively by continuous laser Doppler
      assessment at baseline and during localized heating to 44 degrees C. These
      measurements were repeated 48-72 h following 10 weeks of moderate aerobic
      training performed 3 days per week. Interstitial nitric oxide (NO) levels were
      measured concurrently in the contralateral foot dorsum. Aerobic training did not
      significantly enhance baseline skin perfusion, nor were interstitial NO levels
      different under any condition. At baseline, groups differed only in glycated
      hemoglobin (HbA1c), fasting serum glucose, HDL-cholesterol, and insulin
      resistance. At rest, cutaneous perfusion during local heating to 44 degrees C was
      significantly lower in DS before training, but did not differ significantly from
      CS afterward. Neither group, however, experienced significant increases in dorsal
      foot perfusion during local responsiveness to heating to 44 degrees C following
      10 weeks of moderate aerobic training, despite slightly lower perfusion in DS
      before training; these findings were independent of interstitial NO levels. Thus,
      moderate aerobic training for only 10 weeks does not appear to reverse the
      impairment in cutaneous perfusion of the foot dorsum in response local heating in
      a Type 2 diabetic population.

PMID- 16112504
TI  - Ethnic differences predicting ketonuria in patients with Type 2 diabetes.
AB  - Ketonuria occurs more frequently than ketoacidosis does in patients with Type 2
      diabetes and may portend serious future events. We studied the correlates of
      ketonuria among African American and Hispanic/Latino patients with Type 2
      diabetes who did not have ketoacidosis. METHODS: We performed a retrospective
      cross-sectional study of patients referred for diabetes education from the
      emergency department or the urgent care clinic of a large, public, urban hospital
      from 2001 until 2003. Eligible patients had newly diagnosed Type 2 diabetes or
      diabetes diagnosed within 15 years but without treatment for the previous 2
      months. Using logistic regression analysis, we analyzed the predictors of
      ketonuria and assessed whether they varied by ethnic group. RESULTS: Of 228 adult
      African American and Hispanic/Latino patients, 112 (49%) had ketonuria.
      Independent predictors of ketonuria were younger age (OR: 2.3), higher hemoglobin
      A(1c) (OR: 3.0), and a history of substance abuse (OR: 1.9) (for all: P<.05).
      Among Hispanic/Latino patients, ketonuria was also independently associated with
      low HDL-cholesterol (adjusted OR: 6.6; 95% CI: 2-20), but this relationship was
      not seen in African American patients. CONCLUSIONS: Ketonuria is common among
      newly diagnosed or untreated patients with Type 2 diabetes in a public hospital
      serving a predominantly minority population. Some correlates of ketonuria differ
      among ethnic groups, suggesting potential ethnic differences in ketogenesis.
      Prospective identification and study of patients with ketonuria may have
      important implications for appropriate therapy, especially if it is shown that
      ketonuria is a predictor of symptomatic ketoacidosis.

PMID- 16112505
TI  - Inhibition of MAP-kinase cascade normalizes the proliferation rate of fibroblasts
      from patients with Type 1 diabetes and nephropathy.
AB  - Faster proliferation rate characterizes human skin fibroblasts from patients with
      Type 1 diabetes and nephropathy (DN), but the reason of this phenomenon is still
      unknown. Growth factors control cell proliferation through an intracellular
      mitogen-activated protein (MAP) kinase cascade. We have examined the effect of
      the inhibition of MAP kinase/ERK kinase (MEK), a key point of the MAP kinase
      cascade, on the proliferation rate of fibroblasts from 40 patients with Type 1
      diabetes (20 with and 20 without DN) and from 10 nondiabetic participants.
      Proliferation rate was measured by cell count in the presence or absence of 30
      mumol/l of the MEK inhibitor PD 098059. In normal cultural conditions,
      proliferation rate was faster in fibroblasts from patients with (0.175+/
      0.009x10(5) cells day-1, mean+/-S.E.M.) than without DN (0.110+/-0.009) and in
      nondiabetic participants (0.094+/-0.008; ANOVA P<.0001). The inhibition of MEK
      induced a stronger reduction of proliferation rate in fibroblasts from patients
      with (0.079+/-0.006x10(5) cells day(-1); 55% of reduction) than without DN
      (0.068+/-0.006; 38% of reduction) and in nondiabetic participants (0.064+/-0.006;
      32% of reduction), and differences among groups were lost. In parallel, PD 098059
      induced a greater reduction of MEK-dependent phosphorylation in lysates of
      fibroblasts from patients with (73%) than without (40%) DN. In conclusion, the
      inhibition of MEK normalizes the proliferation rate of fibroblasts from patients
      with DN, suggesting that the MAP kinase cascade could be involved in this
      cellular dysfunction.

PMID- 16112506
TI  - The insulin-like growth factor system and Type 1 diabetic retinopathy during
      pregnancy.
AB  - AIMS/HYPOTHESIS: To find out whether the levels of insulin-like growth factor-I
      (IGF-I), IGF binding protein-1 (IGFBP-1), highly phosphorylated IGFBP-1 (hpIGFBP
      1), and IGF binding protein-3 (IGFBP-3) are related to the progression of
      diabetic retinopathy (DR) during pregnancy and postpartum. METHODS: In a
      prospective study of 42 pregnant women with Type 1 diabetes and 9 nondiabetic
      controls, DR was graded from fundus photographs. Levels of serum total IGF-I and
      two different phosphoisoform patterns of IGFBP-1 and IGFBP-3 were measured during
      the first and third trimester of pregnancy and 3 months postpartum. RESULTS: Both
      the levels of serum total IGF-I (P<.0001) and IGFBP-3 (P=.003) were lower in the
      diabetic than in the nondiabetic women during pregnancy and postpartum (repeated
      measures ANOVA between the groups). Additionally, the IGF-I and IGFBP-3 levels
      tended to be lower in the diabetic women with more severe DR at baseline than in
      those with less severe DR. There were no statistically significant differences in
      the levels of IGF-I and IGFBP-3 in the diabetic women with progression of DR
      compared with those without. No statistical differences appeared in the IGFBP-1
      phosphoisoform patterns between the groups. CONCLUSIONS/INTERPRETATION: In
      diabetic women, mean serum levels of IGF-1 and IGFBP-3 are lower than in
      nondiabetic controls during pregnancy and/or postpartum. Because there was no
      clear connection between the IGF system and progression of DR during pregnancy,
      it is unlikely that these substances mediate the tendency of DR to progress
      during pregnancy.

PMID- 16112507
TI  - Taurine prevents fructose-diet induced collagen abnormalities in rat skin.
AB  - OBJECTIVE: The aim of the study is to investigate the effect of taurine
      administration on the content and characteristics of skin collagen in high
      fructose-fed rats. RESEARCH DESIGN AND METHODS: Adult male Wistar rats were
      divided into four groups of six each: a control group (CON) and a taurine
      supplemented control group (CON+TAU), a high fructose diet-fed group (FRU), and a
      taurine supplemented fructose diet-fed group (FRU+TAU). After 30 days, collagen
      was isolated from the skin, and its physicochemical properties were studied.
      RESULTS: Fructose administration caused an accumulation of collagen and extensive
      cross-linking. This was evidenced by increases in glycation, fluorescence, and
      peroxidation in collagen samples. The physicochemical properties of collagen,
      like shrinkage temperature, aldehyde content, solubility pattern, and
      susceptibility to denaturing agents, were altered in the fructose-fed rats. The
      sodium dodecyl sulphate-polyacrylamide gel electrophoretic (SDS-PAGE) pattern of
      collagen from fructose-fed rats showed and elevated beta component of Type I
      collagen. Simultaneous administration of taurine alleviated these changes.
      CONCLUSION: The positive influence of taurine on both collagen content and its
      properties suggests a potential mechanism for the ability of taurine to delay
      diabetic complications.

PMID- 16112508
TI  - The perception of empty and filled time intervals by rats.
AB  - In Experiment 1, rats were trained in a within-subjects design to discriminate
      durations of a filled interval, and durations of an empty interval (an unfilled
      interval marked at the beginning and end by a 500 ms tone). Training and
      psychophysical testing was conducted with three sets of anchor durations. Rats
      made more long responses for filled than for empty intervals at signal durations
      greater than the geometric mean. In Experiment 2, Group Same was trained
      similarly to the rats in Experiment 1 with the ambient conditions (house light
      illumination) remaining the same during the intertrial interval and the empty
      intervals. Group Different was trained with the house light turned off during
      empty and filled intervals. The similarity of ambient conditions during the
      intertrial interval and the empty intervals did not significantly affect timing.
      Filled intervals were timed more precisely and they were perceived as longer than
      empty intervals of the same duration. The psychophysical functions superimposed
      across anchor duration sets. These results are the first clear evidence of a
      filled interval illusion in rats, and they suggest that this difference may
      reflect a clock rate effect (greater for filled intervals) rather than a switch
      latency effect (slower for empty intervals).

PMID- 16112509
TI  - Interval time-place learning by rats: varying reinforcement contingencies.
AB  - Two experiments with rats were conducted to study interval time-place learning
      when the spatiotemporal contingencies of food availability were more similar to
      those likely to be encountered in natural environments, than those employed in
      prior research. In Experiment 1, food was always available on three levers on a
      variable ratio (VR) 35 schedule. A VR8 schedule was in effect on Lever 1 for 5
      min, then on Lever 2 for 5 min, and so forth. While rats learned to restrict the
      majority of their responding to the lever that provided the highest density of
      reinforcement, they seemed to rely on a win-stay/lose-shift strategy rather than
      a timing strategy. In Experiment 2, the four levers provided food on variable
      ratios of 15, 8, 15, and 30, each for 3 min. As expected the rats learned these
      contingencies. A novel finding was that the rats had a spike in response rate
      immediately following a change from a higher to lower reinforcement density. It
      is concluded that rats exposed to spatiotemporal contingencies behave so as to
      maximize the rate of obtained reinforcement.

PMID- 16112510
TI  - In vivo MR thermometry of frozen tissue using R2* and signal intensity.
AB  - Cryoablation is one of several minimally invasive treatments that may be suitable
      for a targeted treatment of prostate cancer. Because efficacy is improved when a
      sufficiently cold end temperature is reached, the purpose of this work was to
      demonstrate an image-based thermometry method that could provide temperature maps
      throughout the frozen tissue. In five in vivo canine prostate cryoablation
      experiments performed under magnetic resonance imaging guidance, two MR
      parameters were measured and correlated to temperature: R2* and changes in signal
      intensity. R2* is elevated approximately linearly as tissue temperature decreases
      below the freezing point, while the signal intensity decreases exponentially. In
      vivo temperature maps with isotherms at -5 degrees C, -15 degrees C, and -30
      degrees C are demonstrated.

PMID- 16112511
TI  - MR imaging-guided percutaneous angioplasty and stent placement in a swine model
      comparison of open- and closed-bore scanners.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study is to compare the feasibility
      and precision of renal artery angioplasty and stent placement using two different
      MR scanners. MATERIALS AND METHODS: MR imaging-guided angioplasty and stent
      placements were performed on seven pigs using 0.2 and 1.5 T scanners (Magnetom
      Open and Magnetom Sonata, Siemens Medical Solutions, Erlangen, Germany). For
      guidance of catheters, guide wires and stents susceptibility artifact-based
      tracking was used. The end point of each intervention was to position a stent in
      the renal artery with its proximal end at the level of the aortic wall. Procedure
      time and stent position were evaluated. RESULTS: Catheterization, angioplasty,
      and stent placement were feasible using MRI guidance at both 0.2 and 1,5 Tesla.
      At 1.5 T all catheter manipulations and interventions were performed in less than
      30 minutes. At 0.2 T the interventions took up to 90 minutes. No significant
      difference in the stent deviation was noted between the two scanners. CONCLUSION:
      The use of a high-performance 1.5 T scanner helped to reduce the procedure time
      to half of that of a low-field system. Since no difference in stent placement
      precision was noted, a dedicated MR-stent might be mandatory for more precise
      stent placement.

PMID- 16112513
TI  - MR Imaging-guided percutaneous procedures in children.
AB  - Magnetic resonance imaging (MRI)-guided therapeutic interventions in children are
      very rare. In comparison to other imaging techniques, it is very unusual for MRI
      to be used for diagnostic percutaneous interventions despite its imaging
      benefits. We provide a brief description of available MRI systems and instruments
      and use clinical examples to present and discuss typical indications for
      percutaneous procedures while showing possibilities for percutaneous therapeutic
      interventions.

PMID- 16112512
TI  - Real-time, Interactive MRI for cardiovascular interventions.

PMID- 16112514
TI  - Safety protocols for interventional MRI.
AB  - RATIONALE AND OBJECTIVES: To review magnetic resonance safety protocols and
      supplement them for interventional applications. MATERIALS AND METHODS: The
      American College of Radiology White Papers on MR Safety are summarized. Elements
      relevant to interventional MR procedures are emphasized. Additional policies and
      procedures specifically for interventional MR applications covering safety,
      training, and MR compatibility are proposed. RESULTS: A comprehensive operational
      policy for an interventional MR department is proposed. The policies and
      procedures helped our department perform over 400 surgeries and maintain a
      perfect safety record for 5 years. CONCLUSION: Interventional MR departments can
      operate safely but require policies and procedures beyond those required for
      diagnostic MR departments.

PMID- 16112515
TI  - Radiofrequency safety for interventional MRI procedures.

PMID- 16112516
TI  - Computer-assisted diagnosis of focal liver lesions on CT images evaluation of the
      Perceptron algorithm.
AB  - RATIONALE AND OBJECTIVE: The purpose of the study was to investigate a modified
      version of a so-called Perceptron algorithm in detecting focal liver lesions on
      CT scans. MATERIALS AND METHODS: The modified Perceptron algorithm is based on
      simulated annealing with a logarithmic cooling schedule and was implemented on a
      standard workstation. The algorithm was trained with 400 normal and 400
      pathologic CT scans of the liver. An additional 100 normal and 100 pathologic
      scans were then used to test the detection of pathology by the algorithm. The
      total of 1000 scans used in the study were selected from the portal venous phase
      of upper abdominal CT examinations performed in patients with normal findings or
      hypovascularized liver lesions. The pathologic scans contained 1 to 4 focal liver
      lesions. For the preliminary version of the algorithm used in this study, it was
      necessary to define regions of interest that were converted to a matrix of 119 x
      119. RESULTS: Training of the algorithm with 400 examples each of normal and
      abnormal findings took about 75 hours. Subsequently, the testing took several
      seconds for processing each scan. The diagnostic accuracy in discriminating scans
      with and without focal liver lesions achieved for the 200 test scans was
      approximately 99%. The error rate for pathologic and normal scans was comparable
      to results reported in the literature, which, however, were obtained for much
      smaller test sets. CONCLUSION: The modified Perceptron algorithm has an accuracy
      of close to 99% in detecting pathology on CT scans of the liver showing either
      normal findings or hypovascularized focal liver lesions.

PMID- 16112517
TI  - The academic radiologist's clinical productivity: an update.
AB  - RATIONALE AND OBJECTIVES: The purpose of this project was to further understand
      the academic radiologist's clinical workload with comparison to the prior studies
      in the past decade. This updated data is very important in determining faculty
      staffing requirements. MATERIALS AND METHODS: A survey performed by the Society
      of Chairmen of Academic Radiology Departments (SCARD) collected data in 2003 for
      radiologists in 23 departments. This data included Current Procedure Terminology
      (CPT) codes by radiologist. The CPT codes were converted into relative value
      units (RVUs) per full-time equivalent (FTE) faculty. By grouping the CPT codes
      into similar examination categories, adjustment factors were created for the RVU
      values for each CPT in order to compensate for workload variations. These
      adjustment factors are identical to the adjustments made in 2001 except for a new
      factor for nuclear medicine. RESULTS: Overall, the average clinical workload in
      2003 was 5,872 RVU/FTE, a 32% increase compared to 4,458 RVU/FTE in 1998 and 55%
      increase compared to 3,790 RVU/FTE in 1996. The average number of examinations
      per FTE had a smaller (17%) increase since 1998. The adjustment factors remain
      very similar to those presented in 2001. The only change was a new adjustment
      factor of 1.3 for nuclear medicine. CONCLUSIONS: Clinical workload as measured by
      RVU/FTE and adjusted RVU/FTE are very useful for determining optimal staffing in
      subspecialty sections and in the department as a whole. The workload continues to
      increase, but more in examination complexity than in numbers of procedures
      overall.

PMID- 16112518
TI  - The properties of CpG islands in the putative promoter regions of human
      immunoglobulin (Ig) genes.
AB  - CpG island is a GC-rich motif occurred in gene promoter region, which can play
      important roles in gene silencing and imprinting. Here, we present a set of
      discriminant functions that can recognize the structural and compositional
      features of CpG islands in the putative promoter regions (PPRs) of human and
      mouse immunoglobulin (Ig) genes. We showed that the PPRs of both human and mouse
      Ig genes irrespective of gene chromosomal localization are apparently CpG island
      poor, with a low percentage of the CpG islands overlapped with the transcription
      start site (TSS). The human Ig genes that have CpG islands in the PPRs show a
      very narrow range of CpG densities. 47% of the Ig genes fall in the range of 3.5
      4 CpGs/100 bp. In contrast, the non-Ig genes examined have a wide range of the
      density of CpG island, with 10.5% having the density of 8.1-15 CpGs/100 bp.
      Meantime, five patterns of the CpG distributions within the CpG islands have been
      classified: Pat A, B, C, D, and E. 21.6% and 10.8% of the Ig genes fall into the
      Pat B and Pat D groups, respectively, which were significantly higher than the
      non-Ig genes examined (8.2% and 3.8%). Moreover, the length of CpG islands is
      shorter in human Ig genes than in non-Ig genes but is much longer than in mouse
      orthologues. These findings provide a clear picture of non-neutral and nonrandom
      occurrence of the CpG islands in the PPRs of human and mouse Ig genes, which
      facilitate rational recommendations regarding their nomenclature.

PMID- 16112519
TI  - TAGmapper: a web-based tool for mapping SAGE tags.
AB  - Serial Analysis of Gene Expression (SAGE) is an important means of obtaining
      quantitative information about expression of genes in different samples. Short
      SAGE tags are 10 nucleotides long and often contain enough information to
      uniquely identify the gene(s) corresponding to the tag. We have observed,
      however, that the currently available resources are not adequate for accurate
      mapping of all SAGE tags to genes. Here, we describe development of a web-based
      tool called TAGmapper (http://tagmapper.ibioinformatics.org), which provides a
      comprehensive and accurate mapping of SAGE tags to genes. We were able to map
      SAGE tags accurately in several instances where two other popular resources,
      SAGEmap (http://www.ncbi.nlm.nih.gov/projects/SAGE/) and SAGE Genie
      (http://cgap.nci.nih.gov/SAGE), provided incorrect or no assignment of tags to
      genes. Finally, we experimentally determined the expression of a subset of genes
      assigned by TAGmapper using DNA microarrays and/or quantitative PCR to confirm
      the reliability of the gene mappings. We anticipate that TAGmapper will be a
      useful tool in functional genomic approaches by providing accurate identification
      of genes in SAGE experiments.

PMID- 16112520
TI  - Abstracts of the XXIV Annual European Society of Regional Anaesthesia (ESRA)
      Congress, Berlin, Germany, 14-17 September 2005.

PMID- 16112521
TI  - Antimony trioxide-induced apoptosis is dependent on SEK1/JNK signaling.
AB  - Very little is known concerning the toxicity of antimony, despite its commercial
      use as a flame retardant and medical use as a treatment for parasitic infections.
      Our previous studies show that antimony trioxide (Sb(2)O(3)) induces growth
      inhibition in patient-derived acute promyelocytic leukemia (APL) cell lines, a
      disease in which a related metal, arsenic trioxide (As(2)O(3)), is used
      clinically. However, signaling pathways initiated by Sb(2)O(3) treatment remain
      undefined. Here, we show that Sb(2)O(3) treatment of APL cells is associated with
      increased apoptosis as well as differentiation markers. Sb(2)O(3)-induced
      reactive oxygen species (ROS) correlated with increased apoptosis. In addition,
      when we decreased the buffering capacity of the cell by depleting glutathione,
      ROS production and apoptosis was enhanced. Arsenic-resistant APL cells with
      increased glutathione levels exhibited increased cross-resistance to Sb(2)O(3).
      Based on studies implicating c-jun kinase (JNK) in the mediation of the response
      to As(2)O(3), we investigated the role for JNK in Sb(2)O(3)-induced apoptosis.
      Sb(2)O(3) activates JNK and its downstream target, AP-1. In fibroblasts with a
      genetic deletion in SEK1, an upstream regulator of JNK, Sb(2)O(3)-induced growth
      inhibition as well as JNK activation was decreased. These data suggest roles for
      ROS and the SEK1/JNK pathway in the cytotoxicity associated with Sb(2)O(3)
      exposure.

PMID- 16112522
TI  - Estradiol and catecholestrogens protect against adriamycin-induced oxidative
      stress in erythrocytes of ovariectomized rats.
AB  - The beneficial effect of estrogens and catecholestrogens against oxidative stress
      associated tissue injury has been observed in different experimental model. The
      administration of adriamycin (AD) has been shown to enhance oxidative stress in
      different tissues. The lack of estrogens during ovariectomy (OVX) also induces
      oxidative damage in several tissues. However, the antioxidant properties of
      estrogens and catecholestrogens administration have not been evaluated in
      erythrocytes and plasma from ovariectomized animals in presence or not of AD
      toxicity. We have assessed the antioxidant capacity of 17beta-estradiol (17beta)
      and catecholestrogens against oxidative stress in erythrocytes and plasma induced
      by OVX in control animals or AD-treated animals. We analyzed the level of lipid
      peroxides, carbonyl proteins and reduced glutathione (GSH) as well as glutathione
      peroxidase (GPx) and superoxide dismutase (SOD) activities in plasma and
      erythrocytes. The results showed that AD, OVX and its combination increased lipid
      peroxides and carbonyl proteins, as well as reduced glutathione, superoxide
      dismutase and glutathione peroxidase activities in plasma and erythrocytes. The
      administration of 17beta and its metabolites (2- and 4-hydroxyestradiol)
      prevented all markers of oxidative stress induced by OVX in control and AD
      treated animals. In conclusion, the administration of estrogens and
      cathecolestrogens counteract the oxidative stress in erythrocytes and plasma
      induced by OVX in presence or not toxic injury.

PMID- 16112523
TI  - The lived experience post-autologous haematopoietic stem cell transplant (HSCT):
      a phenomenological study.
AB  - Autologous haematopoietic stem cell transplant (HSCT) has a high physical and
      emotional morbidity. This study using Husserlian phenomenological methodology and
      using Giorgi's (Phenomenology and Psychological Research, Dusquesne University
      Press, Pittsburgh, 1985) method of analysis was undertaken to attempt to gain
      some understanding of the patient's experience. Five adult patients who had
      previously undergone autologous transplantation for a haematological malignancy
      at least 6 months before participated in the study. Interviews with the
      participants were audio taped and then transcribed verbatim. Nine themes emerged
      from the participants' stories and included psychological cost, physical and
      psychological adaptation, reprioritisation and a sense of isolation. The
      transplant experience can be separated into a discrete period of time and the
      findings illustrate that the experience of transplantation impacts on the life of
      the person for an undetermined period of time. The changes experienced may be
      permanent and the post-transplant person, emotionally, psychologically and
      physically, is not the same person who entered into transplant. For nurses and
      other health care professionals to improve practice it is imperative that they
      understand the lived experience their patients have undergone. Pretransplant
      preparation and post-transplant rehabilitation can be enhanced by having a
      greater depth of understanding.

PMID- 16112524
TI  - Quality of life of children following bone marrow transplantation: critical
      review of the research literature.
AB  - Children's quality of life (QOL) following bone marrow transplant (BMT) is an
      important but poorly understood concept. The aim of this paper is to critically
      review all research study designs to determine the QOL of childhood BMT
      recipients and to identify implications for research, practice and theory. The
      studies' methodological quality was evaluated separately by two investigators
      according to a set of formal criteria modified from Hoodin and Weber
      (Psychosomatics 44 (2003) 181). The review yielded one retrospective, one cross
      sectional, six descriptive surveys and two prospective longitudinal study
      designs. The studies included 568 childhood BMT recipients ranging from 0.8 to 33
      years. Only one study used a generic and disease-specific, psychometrically
      sound, QOL measure. Timing of assessments ranged from pre-BMT to 21 years
      following BMT. Due to the poor methodological quality, rendering conclusions
      across the studies was challenging. While the available evidence seems to suggest
      children experience good QOL following BMT, several studies found BMT to have a
      negative impact on various aspects of QOL. These results appear to be influenced
      by timing and type of measurements undertaken. Ultimately, there is a need for
      larger, more methodologically rigorous trials using prospective longitudinal
      study designs with pre- and post-measures to examine all QOL domains in children.

PMID- 16112525
TI  - Knowledge of haematological toxicities amongst European nurses--a learning needs
      assessment.
AB  - Haematological toxicities such as neutropenia, anaemia and thrombocytopenia have
      a significant impact on patients with cancer. They can have a life-threatening
      effect on the health of the patient and, importantly, may lead to the
      interruption and/or dose reduction of ongoing cancer therapies, such as
      chemotherapy. Nurses play a pivotal role in haematological toxicity prevention,
      detection and management, however, the current level of involvement and
      understanding varies widely across Europe. Continuing Professional Education
      (CPE) is an important tool in maximising nurses' contributions to such healthcare
      issues, enabling them to maintain awareness of recent research, refreshing their
      knowledge, and facilitating consistency of best practice. As such, the European
      Oncology Nursing Society (EONS) is developing a Europe-wide training programme in
      haematological toxicities. This is based on the unmet CPE needs identified
      through a Learning Needs Assessment (LNA) carried out amongst European cancer
      nurses in 2003. This article discusses the results of the LNA and how the key
      issues that it has revealed are being addressed in EONS' nurse education
      programme, 'Training Initiative in Thrombocytopenia, Anaemia and Neutropenia
      (TITAN)'.

PMID- 16112526
TI  - A grounded theory exploration of the first visit to a cancer clinic--strategies
      for achieving acceptance.
AB  - The purpose of this study was to investigate cancer patients' experiences of
      their first visit to a cancer clinic. Nine patients with various cancer diagnoses
      about to receive curative cancer treatment were interviewed after their first
      visit to the clinic. A qualitative research approach based on Grounded Theory was
      used throughout the research process. The data analysis gave rise to a process
      leading to a core category which showed how patients can reach acceptance of the
      impact cancer has on their lives. Five different categories were identified as
      being important for reaching acceptance, namely action, knowledge, respect,
      continuity and confidence. The patients expressed the need for receiving
      treatment for their cancer without delay, and for continuity in their care. They
      needed to be given individualized, relevant information about their illness and
      to be treated with respect. If these needs were met a feeling of confidence
      resulted. Meeting all of these needs helped patients accept the impact cancer had
      on their lives, as did confidence in the care being given. Acceptance was reached
      when patients felt they could actively participate in treatment decisions, when
      they knew what to expect and when they felt they were being treated as
      individuals. Health care professionals should be aware of these needs, and should
      try to treat their patients as individuals and thus help them to achieve
      acceptance.

PMID- 16112527
TI  - Supportive care: experiences of cancer patients.
AB  - The aim of this study was to explore how cancer patients with progressive disease
      perceived and experienced supportive care at the different stages of their cancer
      journey and to compare this to the perceptions of health care professionals. It
      was a single centre study using qualitative data obtained from two focus group
      interviews in an independent centre for specialist palliative care. Eight
      patients attending the centre were interviewed in two focus groups to ascertain
      their views on the supportive care that they had experienced during the course of
      their illness, focusing on: time of diagnosis, acute treatment phase and
      palliative care phase. Themes that emerged from the analysis of the interview
      transcripts using the QSR NUD*IST (version 4) software package included the
      following: manner in which diagnosis was revealed, information made available to
      family and friends, patients' acceptance of cancer; service provision such as a
      named contact person, choices in treatment and care, problems of limited
      resources; feelings of being unsupported, and ways in which supportive care could
      be improved.

PMID- 16112528
TI  - Developing advanced clinical skills in the management of breathlessness:
      evaluation of an educational intervention.
AB  - The dissemination of knowledge regarding care interventions is often supported
      through educational initiatives. However, the efficacy of education to make a
      difference to practice is not always demonstrated. An educational course has been
      developed and piloted that aimed to educate nurses about skills for the
      management of breathlessness. The course was developed with, and utilised the
      expertise of, researchers, practitioners and educators experienced in the
      management of breathlessness. Twelve clinical nurse specialists, from Scotland
      and South East England, working in oncology and palliative care, participated in
      the first course. A longitudinal evaluation was undertaken to consider the impact
      of the course upon the participants' practice and the care of people who are
      breathless. Interviews were conducted at two time points and a self-rated
      familiarity and confidence tool was completed by the participants at three time
      points. The participants rated themselves as improving their familiarity and
      confidence with the different aspects of the intervention. Attendance on the
      course also impacted upon the care of people who were breathless, improving their
      ability to self-manage their condition. Recommendations for future educational
      developments of this type are provided.

PMID- 16112529
TI  - French field results (1985-2005) on factors affecting fertility of frozen
      stallion semen.
AB  - Results on procedures for freezing stallion semen and the subsequent fertility
      during 20 years are presented. The present system applied in French National Stud
      includes: (1) a freezing protocol (dilution in milk, centrifugation and addition
      of freezing extender (INRA82+egg yolk (2%, v/v)+glycerol (2.5%, v/v) at 22
      degrees C, a moderate cooling rate to 4 degrees C and freezing at -60 degrees
      C/min in 0.5-ml straws); (2) selection of ejaculates showing post-thaw rapid
      motility >35%; and (3) an insemination protocol (mares examined once daily, two
      AI of 400 x 10(6) spermatozoa 24 h apart before ovulation, sufficient number of
      straws to have the possibility to perform six AI of 400 x 10(6) total
      spermatozoa, i.e. 2.4 x 10(9) total spermatozoa available per mare per season).
      This system was applied to >110 stallions per year, the average post-thaw
      motility of ejaculates was 50% (>1800 ejaculates) before selection. The semen
      freezability was defined as the number of selected ejaculates divided by the
      total number of ejaculates frozen. Of the stallions, 5, 4, 5, 21 and 64% had
      semen freezability of 0-10, 10-33, 33-60, 60-90 and over 90%, respectively. Per
      cycle pregnancy rate was 45-48% (>1500 mares per year, 1.8 cycles per mare) and
      foaling rate 64%. In comparison, per-cycle pregnancy rate and foaling rate of
      mares hand-mated to stallions were 57-59% and 64%, respectively. The average
      number of straws used was 32-35 (1.75 x 10(9) total spermatozoa) per mare per
      season. According to our results and the literature, the most important factors
      for improving fertility of frozen equine semen include: (1) a low concentration
      of glycerol (2-3.5% final concentration); (2) a suitable base extender for
      freezing like Lactose-Glucose EDTA or INRA82; (3) a post-thaw motility >30-35%;
      and (4) a sufficient number of spermatozoa per mare per season (1.5-2 x 10(9)
      total spermatozoa for two to three cycles) divided into small units. Numbers of
      spermatozoa, lower than 750.10(6) total spermatozoa per cycle, could result in
      lower per-cycle pregnancy rate with higher additional costs for management of
      mares. Because there are no particular regulations on quality and quantity of
      equine semen in the European Community, there is a need for the uniformity of
      information about frozen semen. A codification is suggested, based on the number
      of spermatozoa available per mare per season, the post-thaw motility and the
      final glycerol concentration.

PMID- 16112531
TI  - Aversive conditioning of periodic spontaneous erection adversely affects sexual
      behavior and semen in stallions.
AB  - Periodic spontaneous erection and penile movements known as masturbation (SEAM)
      occur normally at approximately 90 min intervals in awake equids. SEAM in horses
      has traditionally been misunderstood by many horsemen as aberrant behavior that
      should be eliminated. Accordingly, it is not uncommon for trainers of performance
      stallions or managers of breeding stallions to punish SEAM in an attempt to
      eliminate the behavior. Previous clinical observations and preliminary
      unsystematic trials had suggested that attempts to stop stallion SEAM may lead to
      an increase rather than a decrease in SEAM, and at the same time may suppress
      sexual behavior (SB) in a breeding stallion. The present work evaluated the
      effects of aversive conditioning of SEAM on SEAM, SB, and semen. In Experiment 1,
      four mature pony stallions were subjected to aversive conditioning of SEAM in a
      within- and between-subjects half cross-over design. The SEAM erection interval
      tended to be less after aversive conditioning, suggesting an increase in SEAM
      frequency. Eleven other SEAM measures were each similar before and after aversive
      conditioning of SEAM. In standard sexual behavior trials with a stimulus mare and
      dummy mount, erection latency, ejaculation latency, mount readiness latency, and
      number of mounts to ejaculation increased after aversive conditioning of SEAM;
      erection rigidity score, number of ejaculatory pulses, and vocalization rate
      decreased. Number of thrusts to ejaculation was similar before and after aversive
      conditioning of SEAM. All affected SB measures indicated suppressed sexual
      arousal and breeding efficiency after SEAM. In Experiment 1, ejaculated semen was
      not evaluated. Because in Experiment 1, the number of ejaculatory urethral pulses
      was less after aversive conditioning, Experiment 2 was similarly designed, but
      included evaluation of semen, both immediately and again 1 week after aversive
      conditioning was completed. Experiment 2 included 12 aversively conditioned
      stallions, and 4 yoked controls. In Experiment 2, masturbation episode duration
      tended to be less after aversive conditioning, while the remaining 11 SEAM
      measures were unaffected by aversive conditioning of SEAM. Of SB measures,
      erection latency, mount readiness latency, thrusts to ejaculation, and
      ejaculation latency were significantly greater after aversive conditioning.
      Erection rigidity score and number of ejaculatory pulses were less after aversive
      conditioning. These differences are consistent with suppressed sexual arousal and
      reduced breeding efficiency. Semen volume and total number of sperm per ejaculate
      were significantly less after aversive conditioning. These findings are
      consistent with clinical anecdotes and preliminary trials indicating that
      aversive conditioning of SEAM in stallions suppresses sexual arousal and breeding
      behavior. Of considerable interest both clinically and theoretically, is the
      finding that aversive conditioning target behavior of SEAM was not suppressed by
      aversive conditioning, while SB and semen during semen collection trials were
      both adversely affected.

PMID- 16112532
TI  - Flow rate of some pharmaceutical diluents through die-orifices relevant to mini
      tableting.
AB  - The effects of cylindrical orifice length and diameter on the flow rate of three
      commonly used pharmaceutical direct compression diluents (lactose, dibasic
      calcium phosphate dihydrate and pregelatinised starch) were investigated, besides
      the powder particle characteristics (particle size, aspect ratio, roundness and
      convexity) and the packing properties (true, bulk and tapped density). Flow rate
      was determined for three different sieve fractions through a series of miniature
      tableting dies of different orifice diameter (0.4, 0.3 and 0.2 cm) and thickness
      (1.5, 1.0 and 0.5 cm). It was found that flow rate decreased with the increase of
      the orifice length for the small diameter (0.2 cm) but for the large diameter
      (0.4 cm) was increased with the orifice length (die thickness). Flow rate changes
      with the orifice length are attributed to the flow regime (transitional arch
      formation) and possible alterations in the position of the free flowing zone
      caused by pressure gradients arising from the flow of self-entrained air, both
      above the entrance in the die orifice and across it. Modelling by the
      conventional Jones-Pilpel non-linear equation and by two machine learning
      algorithms (lazy learning, LL, and feed-forward back-propagation, FBP) was
      applied and predictive performance of the fitted models was compared. It was
      found that both FBP and LL algorithms have significantly higher predictive
      performance than the Jones-Pilpel non-linear equation, because they account both
      dimensions of the cylindrical die opening (diameter and length). The automatic
      relevance determination for FBP revealed that orifice length is the third most
      influential variable after the orifice diameter and particle size, followed by
      the bulk density, the difference between bulk and tapped densities and the
      particle convexity.

PMID- 16112533
TI  - The commercial harvest of devil's claw (Harpagophytum spp.) in southern Africa:
      the devil's in the details.
AB  - Devil's claw is the common name for two species in the genus Harpagophytum. Their
      root extracts contain the iridoid glycoside, harpagoside, which has been found to
      be effective in the treatment of degenerative rheumatoid arthritis,
      osteoarthritis, tendonitis, kidney inflammation, and heart disease. Most of the
      world's supply comes from Namibia, with lesser amounts from South Africa and
      Botswana. In 2002, the peak year of export, 1018 tonnes of dried tubers were
      exported from southern Africa, representing the harvest of millions of plants. In
      2001, sales in Germany were estimated at 30 M euros, accounting for 74% of the
      prescriptions for rheumatism. Harvest has improved income levels in marginalized
      communities but it has also raised questions of sustainability. In 2000,
      recommendations were made to the Convention on the International Trade in
      Endangered Species (CITES) to add devil's claw to Appendix II. In 2004, the
      proposal was formally withdrawn due to the efforts of the range states to address
      sustainability issues. Replacing wild collection with cultivation has generated a
      debate on the positive and negative effects on harvester income and rural
      farmers. Successful cultivation efforts have involved micropropagation techniques
      and growing the plant without water or fertilizers. The governments of the main
      range states are working with local communities to develop policies and
      regulations to protect the species and to determine a sustainable harvest.

PMID- 16112534
TI  - LC-MS/MS determination of the HIV-1 protease inhibitor indinavir in brain and
      testis of mice.
AB  - A rapid and sensitive method for the determination of indinavir in mice brain and
      testis is described and validation data are provided. Indinavir and the internal
      standard (IS) amprenavir were isolated from homogenized tissue matrices using a
      mixed-mode solid-phase extraction (SPE) procedure and were then analyzed by
      reversed-phase liquid chromatography/tandem mass spectrometry (LC-MS/MS). The
      mass spectrometer in the positive-ion multiple reaction monitoring mode used
      pairs of ions at m/z of 614.1/421.3 for indinavir and of 506.1/245.3 for IS. The
      calibration curves were linear over the range 0.0012-0.0390 micromol/kg for brain
      and 0.39-12.50 micromol/kg for testis. Linearity, repeatability and accuracy were
      validated. The applicability of the method was demonstrated by assessing
      indinavir in brain and testis of three mice dosed with intravenous bolus
      administration of indinavir (16.3 micromol/kg).

PMID- 16112535
TI  - Non-enzymatic glutathione reactivity and in vitro toxicity: a non-animal approach
      to skin sensitization.
AB  - The development of non-animal methods to predict the potential of chemicals to
      cause skin sensitization is of great importance. On the basis of many published
      studies into the underlying chemical mechanisms skin sensitization, the
      immunological priming which leads to the disease allergic contact dermatitis, is
      recognized as a reactive chemistry endpoint. Consequently, the combination of
      chemical assays with in vitro techniques may provide a useful surrogate to animal
      testing for skin sensitization. This study attempts to investigate the
      relationship between skin sensitization assessed in the local lymph node assay
      (LLNA) initially and a thiol reactivity index based on glutathione (GSH), pEC(50)
      thiol (EC(50) being defined as the concentration of the test substance which
      gives 50% depletion of free thiol under standard conditions) in combination with
      a measure of cytotoxicity (pIGC(50)) to Tetrahymena pyriformis (TETRATOX). The
      pEC(50) thiol values and the pIGC(50) values were determined for twenty-four
      compounds for which LLNA test data were available. Thiol reactivity was found to
      discriminate sensitizers from non-sensitizers according to the rule: pEC(50)
      thiol>-0.55 indicates that the compound will be a skin sensitizer. However,
      because of metabolic activation a pEC(50) thiol<-0.55 does not necessarily mean
      that the compound will be a non-sensitizer. Excess toxicity to T. pyriformis
      (i.e. the extent of toxic potency over that expected by non-polar narcosis) was
      determined in order to assess biological reactivity. The best discrimination
      based on excess toxicity in the TETRATOX assay was given by the "rule": excess
      toxicity>0.50 indicates that the compound will be a skin sensitizer. These
      approaches become more powerful when combined. When taken together, the thiol and
      TETRATOX assays predict the sensitization potential of 23 of the 24 compounds
      correctly. alpha-Hexylcinnamic aldehyde is incorrectly predicted to be a non
      sensitizer, whereas LLNA results suggest it may be a weak sensitizer, this
      inaccuracy being rationalized in terms of its high hydrophobicity. Due to the
      selectivity of electro(nucleo)philic reactions some sensitizing compounds will
      not be identified using a single nucleophile such as thiol.

PMID- 16112536
TI  - Effect of myrrh oil on IL-1beta stimulation of NF-kappaB activation and PGE(2)
      production in human gingival fibroblasts and epithelial cells.
AB  - Anecdotal and scientific evidence suggest that myrrh oil (MO) has anti
      inflammatory properties. Subtoxic MO levels decrease interleukin (IL)-1beta
      stimulated production of the inflammatory cytokine IL-6 by human gingival
      fibroblasts, but not epithelial cells. IL-1beta upregulates IL-6 via PGE(2), and
      via NF-kappaB, a transcription factor for many inflammatory mediator genes. NF
      kappaB is inhibited by sesquiterpene compounds (from plants other than myrrh).
      This study determined MO effect on IL-1beta-stimulated PGE(2) production and NF
      kappaB activation in gingival fibroblasts and epithelial cells. Cells were
      preincubated with MO, exposed to IL-1beta, cytoplasmic and nuclear fractions were
      isolated, and activated NF-kappaB was measured using an ELISA-based assay. IL
      1beta increased nuclear activated NF-kappaB levels in fibroblasts and epithelial
      cells [10- and 2.5-fold over controls, respectively (p=0.0001)], and these
      increases were not significantly affected by MO. PGE(2) was measured in cell
      supernatants by ELISA, after preincubation with MO and exposure to IL-1beta. MO
      inhibited IL-1beta-stimulated PGE(2) production by fibroblasts (p=0.001), but not
      epithelial cells. The data suggest that gingival epithelial cells and fibroblasts
      may differ in the magnitude of NF-kappaB activation after IL-1beta stimulation,
      and that MO inhibition of IL-1beta-stimulated IL-6 production in fibroblasts is
      due in part to inhibition of PGE(2), but not NF-kappaB activation. (Supported by
      NIDCR DE-0725.).

PMID- 16112537
TI  - Thirteenth International Workshop on In Vitro Toxicology.

PMID- 16112538
TI  - High concentrations of pralidoxime are needed for the adequate reactivation of
      human erythrocyte acetylcholinesterase inhibited by dimethoate in vitro.
AB  - Due to the current controversy about the real effectiveness of the oximes in the
      treatment of organophosphate poisoning, the reactivation capacity of pralidoxime
      has been evaluated in vitro on human erythrocyte acetylcholinesterase inhibited
      by dimethoate. In the in vitro model, a partial recovery of acetylcholinesterase
      activity was observed with concentrations from 0.066 mM pralidoxime, probably
      useful enough to prevent death in most cases in vivo. However, much more
      effectiveness was observed with concentrations up to 0.70 mM pralidoxime.
      Although pralidoxime should be applied as soon as possible after organophosphate
      exposure, the application of the antagonist can be useful even 24h after,
      particularly for organophosphates with biological half-life longer than one day.
      The protective capacity of pralidoxime after the application was reduced up to
      50% in 6h and disappeared almost completely in 24h. Furthermore, the pesticide
      and its metabolites remained active and were able to inhibit the enzyme as soon
      as pralidoxime reduced its antagonist capacity. Our results in conjunction with
      the short half-life of pralidoxime suggest that the maintenance of higher
      plasmatic concentrations than the currently used should be considered in the
      management of severe poisoned patients, although adverse effects could be
      expected.

PMID- 16112539
TI  - Who is best at predicting children's anxiety in response to a social evaluative
      task? A comparison of child, parent, and teacher reports.
AB  - The purpose of this preliminary study was to examine the validity of child,
      parent, and teacher reports of child social anxiety in predicting the child's
      responses to a social evaluative task. Children, parents, and teachers each
      completed a measure of social anxiety, as well as a measure that asked them to
      predict the child's anxiety during a behavioral approach task (BAT) of reading
      aloud in front of a video camera. Consistent with previous literature, analyses
      revealed poor agreement across informants. Importantly, children's reports
      predicted their own anxious feelings and, to some degree, their behaviors during
      the task, whereas other informants' reports did not. We recommend that further
      research examine the relative validity of multiple informants' reports in
      predicting children's real-life behavior.

PMID- 16112540
TI  - Maternal knowledge, attitude and practice on folic acid intake among Arabian
      Qatari women.
AB  - BACKGROUND: Periconceptional folic acid supplementation is effective in
      preventing primary and secondary neural tube defects (NTDs) and other congenital
      defects. It is important to estimate folate intake and knowledge in women of
      child-bearing age, in relation to risk of congenital anomalies. AIM: The aim of
      this study was to determine the level of knowledge about the usefulness of
      periconceptional folic acid supplementation in a sample of women in the child
      bearing age. DESIGN: This is a cross-sectional survey. SETTING: Eleven primary
      health care centers and women's hospital in Qatar. SUBJECTS: A multistage
      sampling design was used and a representative sample of 1,800 Qatari women aged
      between 18 and 45 years were surveyed during the period June to November 2004.
      One thousand four hundred and eighty women (82.2%) expressed their consent to
      participate in this study. METHODS: A confidential, anonymous questionnaire was
      completed by the selected subjects assessing folic acid awareness. Questionnaires
      were administered to women who were seeking routine antenatal care at health
      centers and Women's Hospital. Questions covered knowledge and use of folic acid
      supplements, pregnancy intention, and demographic and socioeconomic
      characteristics. Factors affecting study outcomes were examined individually by
      computing crude odd ratios and adjusted for other covariates using unconditional
      logistic regression. RESULTS: Out of 1480 women surveyed, 53.7% of them reported
      that they heard of folate. Of these, only half of the subjects knew that folate
      was something important. Overall, 20.3% of the respondents took folic acid. The
      most common information sources on folate were physicians (63.4%), and
      newspapers/magazine/books (21.7%). From those who heard of folate, only 14% knew
      that it can prevent birth defects. 40.6% of the subjects who heard folate were
      aware that green leafy vegetables were fortified with folic acid. In univariate
      analysis, awareness of folic acid was significantly associated with education of
      mother. Again, higher educated women (41.3%) knew more about folic acid and used
      it more often in the periconceptional and first trimester period. CONCLUSION:
      Awareness and use of folic acid was less prevalent among Qatari women. Educated
      women were aware of the importance of the intake of folic acid. The study
      findings suggested possible avenue for intervention to increase awareness and
      intake of folic acid.

PMID- 16112541
TI  - Xenobiotic phenols in early pregnancy amniotic fluid.
AB  - We found detectable levels of three phytoestrogens (enterolactone, daidzein and
      genistein) and bisphenol A (BPA) in 21 residual amniotic fluid specimens that
      were collected before 20 weeks gestation. Samples were obtained by amniocentesis
      from women who were referred to the Mount Sinai Medical center because of
      advanced maternal age. Phytoestrogens were present in higher concentrations than
      BPA. Enterolactone was detected at the highest concentration (median 95.9
      microg/L), followed by daidzein and genistein (9.5 and 1.4 microg/L,
      respectively). BPA was present at very low concentrations (10%>LOD of 0.5
      microg/L). The relative concentration of the chemicals measured in amniotic fluid
      were identical to those in urine reported by other studies, i.e.
      enterolactone>daidzein>genistein>>BPA. Amniotic fluid is a source of fetal
      exposure to polar xenobiotics that come from the mother.

PMID- 16112543
TI  - Inspiratory muscle training in exercise-induced paradoxical vocal fold motion.
AB  - The purpose of the study was to determine if inspiratory muscle training (IMT)
      would result in increased inspiratory muscle strength, reduced perception of
      exertional dyspnea, and improved measures of maximal exercise effort in an
      athlete with exercise-induced paradoxical vocal fold motion (PVFM). The
      participant, an 18-year-old woman, had a 2-year history of acute dyspnea with
      exertion during soccer games. Spirometry, transnasal flexible laryngoscopy, and
      patient history supported a PVFM diagnosis. The ABAB within-subject withdrawal
      design study comprised IMT treatment and withdrawal phases, each lasting 5 weeks.
      The participant trained 5 days per week, completing five sets of 12 breaths at
      75% maximum inspiratory pressure (MIP) per session. Data consisted of MIP,
      exertional dyspnea ratings, and maximal exercise measures. IMT resulted in
      increased MIP and decreased dyspnea ratings across both treatment phases. No
      change in MIP or dyspnea ratings occurred in response to treatment withdrawal.
      The maximal exercise test revealed minimal changes across phases. At end of the
      study, the participant reported experiencing no PVFM symptoms when performing the
      outcome measurement tasks and when playing soccer. Transnasal flexible
      laryngoscopy, after strenuous exercise and during rapid breathing and phonation
      tasks, revealed normal laryngeal findings. The findings suggest that IMT may be a
      promising treatment approach for athletes with exercise-induced PVFM.

PMID- 16112542
TI  - Lipoic acid modulates adriamycin-induced testicular toxicity.
AB  - Adriamycin (ADR), an anthracycline antibiotic, which is widely used as an
      antineoplastic drug in the treatment of various solid tumors, has been shown to
      induce reproductive abnormalities in males. In the present study, the effect of
      lipoic acid (LA) a universal antioxidant was investigated on ADR-induced
      testicular toxicity in rats. Adult male albino rats of Wistar strain were
      administered ADR (1mg/kg body weight, i.v.), once a week for 10 weeks. ADR
      injected rats showed increased levels of 8-hydroxy-2-deoxyguanosine with high
      protein carbonyl contents in testicular tissue. These changes were associated
      with significant increase in DNA damage in the sperm as evidenced by increased
      single strand breaks in a fluorimetric analysis of DNA unwinding (FADU). The
      activities of steroidogenic enzymes such as 3beta-hydroxy steroid dehydrogenase
      and 17beta-hydroxy steroid dehydrogenase, serum testosterone levels were
      decreased significantly in ADR-treated rats. Flow cytometric evaluation of
      testicular tissue in ADR-administered rats revealed impaired spermatogenesis and
      testicular function. Treatment with lipoic acid (35 mg/kg body weight, i.p.) one
      day prior to ADR administration, maintained near normal steroidogenesis and
      spermatogenesis, thereby proving it to be an effective cytoprotectant.

PMID- 16112545
TI  - Aerodynamic analysis of male-to-female transgender voice.
AB  - The attainment of a feminine-sounding voice is a highly desirable goal among male
      to-female transgender (MFT) persons, but this goal may be difficult for many to
      accomplish. The characteristics associated with a feminine vocal quality include
      increases in fundamental frequency and in vocal breathiness. In this study, we
      used inverse-filtering of the airflow signal to indirectly assess vocal fold
      function in 13 MFT persons. Each participant was asked to sustain the vowel /a/
      first in her biological male voice and then again in her female voice. In
      addition, these vowel productions were compared with vowels produced by age
      matched biologic women and men. The results of the study revealed a significant
      increase in maximum flow declination rate during female voice production.
      Perceptual ratings of a feminine voice were associated with a fundamental
      frequency (F0) of 180 Hz or greater, although F0 did not differ significantly
      between male and female voice production. These results are discussed relative to
      the mechanisms that obtained a feminine-sounding voice.

PMID- 16112544
TI  - Preliminary results of a new temporary vocal fold injection material.
AB  - Temporary vocal fold injection is a valuable procedure for vocal fold paralysis
      or paresis of uncertain permanency and as a trial augmentation to decide the
      value of vocal fold augmentation. A new material made from glycerin,
      carboxymethylcellulose, and water has recently been developed for temporary vocal
      fold augmentation. Eleven patients underwent vocal fold injection for the
      treatment of glottal incompetence with this material. The duration of
      effectiveness of this injection material was 2 to 3 months depending on the
      injection amount. This new material satisfies several requirements for an ideal
      temporary vocal fold injection material in terms of injectability, convenience,
      duration of effectiveness, and safety. The authors conclude that this new
      material is a good option for temporary vocal fold augmentation.

PMID- 16112546
TI  - Neural network model for extracting optic flow.
AB  - When we travel in an environment, we have an optic flow on the retina. Neurons in
      the area MST of macaque monkeys are reported to have a very large receptive field
      and analyze optic flows on the retina. Many MST-cells respond selectively to
      rotation, expansion/contraction and planar motion of the optic flow. Many of them
      show position-invariant responses to optic flow, that is, their responses are
      maintained during the shift of the center of the optic flow. It has long been
      suggested mathematically that vector-field calculus is useful for analyzing optic
      flow field. Biologically, plausible neural network models based on this idea,
      however, have little been proposed so far. This paper, based on vector-field
      hypothesis, proposes a neural network model for extracting optic flows. Our model
      consists of hierarchically connected layers: retina, V1, MT and MST. V1-cells
      measure local velocity. There are two kinds of MT-cell: one is for extracting
      absolute velocities, the other for extracting relative velocities with their
      antagonistic inputs. Collecting signals from MT-cells, MST-cells respond
      selectively to various types of optic flows. We demonstrate through a computer
      simulation that this simple network is enough to explain a variety of results of
      neurophysiological experiments.

PMID- 16112547
TI  - Interactive image data labeling using self-organizing maps in an augmented
      reality scenario.
AB  - We present an approach for the convenient labeling of image patches gathered from
      an unrestricted environment. The system is employed for a mobile Augmented
      Reality (AR) gear: while the user walks around with the head-mounted AR-gear,
      context-free modules for focus-of-attention permanently sample the most
      'interesting' image patches. After this acquisition phase, a Self-Organizing Map
      (SOM) is trained on the complete set of patches, using combinations of MPEG-7
      features as a data representation. The SOM allows visualization of the sampled
      patches and an easy manual sorting into categories. With very little effort, the
      user can compose a training set for a classifier, thus, unknown objects can be
      made known to the system. We evaluate the system for COIL-imagery and demonstrate
      that a user can reach satisfying categorization within few steps, even for image
      data sampled from walking in an office environment. (An abbreviated version of
      some portions of this article appeared in [Bekel, H., Heidemann, G., & Ritter, H.
      (2005). SOM Based Image Data Structuring in an Augmented Reality Scenario. In
      Proceedings of the International Joint Conference on Neural Networks, Montreal,
      Canada.], as part of the IJCNN 2005 conference proceedings, published under the
      IEEE copyright).

PMID- 16112548
TI  - Subfield variations in hippocampal processing-components of a spatial navigation
      system.
AB  - The hippocampus is a part of the brain strongly linked to spatial exploration.
      Within it exist 'place cells' which fire preferentially when an animal is in
      certain regions of physical space. Recent research has shown that these place
      cells and their corresponding representations of space behave differently in the
      CA3 and CA1 subfields of the hippocampus. We review this research and show, by
      simulation, that these differences can be explained by a combination of known
      physiological features of the hippocampus and proposed variations in the rate of
      synaptic plasticity and connection strength between different information
      pathways. We suggest possible reasons for these differences, namely use of the
      CA1 cell field for current spatial exploration, and CA3 for longer term spatial
      memory.

PMID- 16112549
TI  - Framewise phoneme classification with bidirectional LSTM and other neural network
      architectures.
AB  - In this paper, we present bidirectional Long Short Term Memory (LSTM) networks,
      and a modified, full gradient version of the LSTM learning algorithm. We evaluate
      Bidirectional LSTM (BLSTM) and several other network architectures on the
      benchmark task of framewise phoneme classification, using the TIMIT database. Our
      main findings are that bidirectional networks outperform unidirectional ones, and
      Long Short Term Memory (LSTM) is much faster and also more accurate than both
      standard Recurrent Neural Nets (RNNs) and time-windowed Multilayer Perceptrons
      (MLPs). Our results support the view that contextual information is crucial to
      speech processing, and suggest that BLSTM is an effective architecture with which
      to exploit it.

PMID- 16112550
TI  - Generalized 2D principal component analysis for face image representation and
      recognition.
AB  - In the tasks of image representation, recognition and retrieval, a 2D image is
      usually transformed into a 1D long vector and modelled as a point in a high
      dimensional vector space. This vector-space model brings up much convenience and
      many advantages. However, it also leads to some problems such as the Curse of
      Dimensionality dilemma and Small Sample Size problem, and thus produces us a
      series of challenges, for example, how to deal with the problem of numerical
      instability in image recognition, how to improve the accuracy and meantime to
      lower down the computational complexity and storage requirement in image
      retrieval, and how to enhance the image quality and meanwhile to reduce the
      transmission time in image transmission, etc. In this paper, these problems are
      solved, to some extent, by the proposed Generalized 2D Principal Component
      Analysis (G2DPCA). G2DPCA overcomes the limitations of the recently proposed
      2DPCA (Yang et al., 2004) from the following aspects: (1) the essence of 2DPCA is
      clarified and the theoretical proof why 2DPCA is better than Principal Component
      Analysis (PCA) is given; (2) 2DPCA often needs much more coefficients than PCA in
      representing an image. In this work, a Bilateral-projection-based 2DPCA (B2DPCA)
      is proposed to remedy this drawback; (3) a Kernel-based 2DPCA (K2DPCA) scheme is
      developed and the relationship between K2DPCA and KPCA (Scholkopf et al., 1998)
      is explored. Experimental results in face image representation and recognition
      show the excellent performance of G2DPCA.

PMID- 16112551
TI  - Improving dimensionality reduction with spectral gradient descent.
AB  - We introduce spectral gradient descent, a way of improving iterative
      dimensionality reduction techniques. The method uses information contained in the
      leading eigenvalues of a data affinity matrix to modify the steps taken during a
      gradient-based optimization procedure. We show that the approach is able to speed
      up the optimization and to help dimensionality reduction methods find better
      local minima of their objective functions. We also provide an interpretation of
      our approach in terms of the power method for finding the leading eigenvalues of
      a symmetric matrix and verify the usefulness of the approach in some simple
      experiments.

PMID- 16112552
TI  - Refining competition in the self-organising tree map for unsupervised biofilm
      image segmentation.
AB  - The Self Organising Tree Map (SOTM) neural network is investigated as a means of
      segmenting micro-organisms from confocal microscope image data. Features
      describing pixel and regional intensities, phase congruency and spatial proximity
      are explored in terms of their impact on the segmentation of bacteria and other
      micro-organisms. The significance of individual features is investigated, and it
      is proposed that, within the context of micro-biological image segmentation,
      better object delineation can be achieved if certain features are more dominant
      in the initial stages of learning. In this way, other features are allowed to
      become more/less significant as learning progresses: as more knowledge is
      acquired about the data being segmented. We argue that the efficiency and
      flexibility of the SOTM in adapting to, and preserving the topology of input
      space, makes it an appropriate candidate for implementing this idea. We propose a
      refinement to the competitive search strategy that allows for a more appropriate
      fusion of signal and proximal features, thereby promoting a segmentation that is
      more sensitive to the regional associations of different microbial matter. A
      refined stop criterion is also suggested such that the dynamically generated
      number of classes becomes more data dependant. Preliminary experiments are
      presented and it is found that favouring intensity characteristics in the early
      phases of learning, whilst relaxing proximity constraints in later phases of
      learning, offers a general mechanism through which we can improve the
      segmentation of microbial constituents.

PMID- 16112553
TI  - The control of a parallel hybrid-electric propulsion system for a small unmanned
      aerial vehicle using a CMAC neural network.
AB  - A Simulink model, a propulsion energy optimization algorithm, and a CMAC
      controller were developed for a small parallel hybrid-electric unmanned aerial
      vehicle (UAV). The hybrid-electric UAV is intended for military, homeland
      security, and disaster-monitoring missions involving intelligence, surveillance,
      and reconnaissance (ISR). The Simulink model is a forward-facing simulation
      program used to test different control strategies. The flexible energy
      optimization algorithm for the propulsion system allows relative importance to be
      assigned between the use of gasoline, electricity, and recharging. A cerebellar
      model arithmetic computer (CMAC) neural network approximates the energy
      optimization results and is used to control the parallel hybrid-electric
      propulsion system. The hybrid-electric UAV with the CMAC controller uses 67.3%
      less energy than a two-stroke gasoline-powered UAV during a 1-h ISR mission and
      37.8% less energy during a longer 3-h ISR mission.

PMID- 16112554
TI  - Model of multi-modal cortical processing: coherent learning in self-organizing
      modules.
AB  - In this paper (An abbreviated version of some portions of this article appeared
      in reference Menard and Frezza-Buet (Menard, O., & Frezza-Buet, H. (2004).
      Rewarded multi-modal neuronal self-organization: Example of the arm reaching
      movement. In: Proceedings of international conference on advances in intelligent
      systems theory and application.), as part of the IJCNN 2005 conference
      proceedings, published under the IEEE copyright.), an original self-organizing
      model is presented, with experiments highlighting its ability to be used in
      different frameworks, as phonetic coding dependent on semantics and arm-reaching.
      The model relies on the coupling of the learning processes that stand at
      different self-organizing modules, and exhibits dynamics that can be discussed in
      terms of the binding of different modalities, scattered over the different
      modules. Such a binding property is based on an emerging constraint of keeping
      consistency between the modules. This process is induced by partial connectivity
      and appropriate neural field competition mechanisms.

PMID- 16112555
TI  - The contribution of active body movement to visual development in evolutionary
      robots.
AB  - Inspired by the pioneering work by Held and Hein (1963) on the development of
      kitten visuo-motor systems, we explore the role of active body movement in the
      developmental process of the visual system by using robots. The receptive fields
      in an evolved mobile robot are developed during active or passive movement with a
      Hebbian learning rule. In accordance to experimental observations in kittens, we
      show that the receptive fields and behavior of the robot developed under active
      condition significantly differ from those developed under passive condition. A
      possible explanation of this difference is derived by correlating receptive field
      formation and behavioral performance in the two conditions.

PMID- 16112556
TI  - GDF-5 deficiency alters stress-relaxation properties in mouse skin.

PMID- 16112557
TI  - Sex-dependent effects of fluoxetine and triiodothyronine in the forced swim test
      in rats.
AB  - The effects of triiodothyronine (T3) and fluoxetine, administered separately and
      combined, on behavior of male and female rats in the forced swim test, a
      procedure for screening antidepressant-like activity, were determined. There were
      no consistent effects of low doses of fluoxetine (5 mg/kg) or T3 (20 microg/kg),
      administered daily for 2 weeks. Fluoxetine administered daily at 10 mg/kg for 7
      days reduced immobility and increased active behaviors in male rats, but had no
      effects in female rats. The effects of fluoxetine in male rats were not
      potentiated by T3. In female rats, T3 at 100 microg/kg given daily for 7 days
      decreased immobility and increased swimming when these were measured 72 h after
      the last injection, but not when measurements were performed at an earlier time
      point. These results provide some support from an animal model for the efficacy
      of T3 as antidepressant therapy in female patients, but do not provide support
      for the augmentation and acceleration effects seen clinically when T3 is used in
      conjunction with established antidepressants such as fluoxetine.

PMID- 16112558
TI  - Effect of vitamin E on memory retention in rats: possible involvement of
      cholinergic system.
AB  - This study concerned effects of vitamin E and the cholinergic system on memory
      retention of passive avoidance learning in rats. Post-training
      intracerebroventricular (i.c.v.) injections were carried out in all experiments.
      Administrations of vitamin E (10, 25 and 50 microg/rat), nicotine (0.1
      microg/rat) and pilocarpine (0.5 microg/rat), the muscarinic receptor agonist
      increased memory retention, while mecamylamine (0.01, 0.1 and 0.5 microg/rat),
      the nicotinic receptor antagonist and scopolamine (0.1, 1 and 5 microg/rat), the
      muscarinic receptor antagonist decreased memory retention. The combination of
      vitamin E with nicotine or pilocarpine showed potentiation. Effects of
      mecamylamine or scopolamine were attenuated by vitamin E. It is concluded that
      vitamin E has a close interaction with cholinergic system in memory retention
      process.

PMID- 16112559
TI  - Effect of molecular weight heterogeneity on drug encapsulation efficiency of
      gelatin nano-particles.
AB  - Influence of molecular weight heterogeneity and drug solubility, drug loading and
      hydrodynamic conditions on drug release kinetics from gelatin nanoparticles were
      investigated. Also to assess the ability of gelatin nanoparticles as a potential
      intravascular probe for diagnostic purposes and in improving the biodelivery of
      cycloheximide (CHX), which is being used as a representative drug. Comparative
      characterization of 75 Bloom (type B, bovine), 175 and 300 Bloom (type A,
      porcine) gelatin nanoparticles was done to understand the phase behavior and
      hydrodynamic properties of gelatin chains and its nanoparticles. Gelatin
      nanoparticles were prepared by two-step desolvation method. Dynamic light
      scattering studies were performed to estimate hydrodynamic radii as well as
      intermolecular interaction. Effects of parameters like pH, temperature and
      molecular weight on the size and stability of the nanoparticles were studied.
      Transmission electron microscopy (TEM) and atomic force microscopy (AFM)
      measurements were done for size and stability analysis. Enhanced visco-elastic
      properties of nanoparticles were observed as compared to normal solutions of
      gelatin.

PMID- 16112560
TI  - Synovial biology and T cells in rheumatoid arthritis.
AB  - Events that occur in rheumatoid arthritis synovial tissues are responsible for
      the signs and symptoms of joint inflammation and for the eventual destruction of
      articular and periarticular structures that lead to joint dysfunction and
      disability. The three most abundant cell populations in RA synovium are synovial
      macrophages (type A synoviocytes), synovial fibroblasts (type B synoviocytes) and
      infiltrating T lymphocytes. Other important cell populations include B
      lymphocytes, dendritic cells, plasma cells, mast cells and osteoclasts. Our
      current understanding of rheumatoid arthritis is moving beyond previous concepts
      that view this disease as the consequence of a specific and focused humoral or
      cellular autoimmune response to a single autoantigen. Rather, a new view of
      rheumatoid arthritis is emerging, which seeks to understand this disease as the
      product of pathologic cell-cell interactions occurring within a unique and
      defined environment, the synovium. T lymphocytes in rheumatoid arthritis synovium
      interact closely with dendritic cells, the most potent antigen-presenting cell
      population in the immune system. T cells also interact with monocytes and
      macrophages and cytokine-activated T cells may be, especially, suited to trigger
      production of the important cytokine TNFalpha by synovial macrophages. Recent
      evidence also suggests a potent bidirectional interaction between synovial T
      cells and synovial fibroblasts, which can lead to activation of both cell types.
      An important role for synovial B lymphocytes has been emphasized recently, both
      by experimental data and by results of clinical interventions. B cells in
      synovium can interact with fibroblasts as well as with other cells of the immune
      system and their potential role as antigen-presenting cells in the joint is as
      yet underexplored. Rheumatoid arthritis synovium may be one of the most striking
      examples of pathologic, organ-specific interactions between immune system cells
      and resident tissue cell populations. This view of rheumatoid arthritis also
      leads to the prediction that novel approaches to treatment will more logically
      target the intercellular communication systems that maintain such interactions,
      rather than attempt to ablate a single cell population.

PMID- 16112561
TI  - The challenges of abundance: epithelial junctions and small GTPase signalling.
AB  - Small GTPases of the Ras superfamily play critical roles in epithelial
      biogenesis. Many key morphogenetic functions occur when small GTPases act at
      epithelial junctions, where they mediate an increasingly complex interplay
      between cell-cell adhesion molecules and fundamental cellular processes, such as
      cytoskeletal activity, polarity and trafficking. Important recent advances in
      this field include the role of additional members of the Ras superfamily in cell
      cell contact stability and the capacity for polarity determinants to regulate
      small GTPase signalling. Interestingly, small GTPases may participate in the
      cross-talk between different adhesive receptors: in tissues classical cadherins
      can selectively regulate other junctions through cell signalling rather than
      through a global influence on cell-cell cohesion.

PMID- 16112562
TI  - Management approaches to integrated solid waste in industrialized zones in
      Jordan: a case of Zarqa City.
AB  - There is a need to recognize the difficulties experienced in managing waste and
      to understand the reasons for those difficulties, especially in developing
      countries such as Jordan. Zarqa is a Governorate located in central Jordan, which
      has 2874 registered industries, making up more than 52% of the total industries
      in the country. Zarqa Governorate suffers from serious solid waste problems.
      These problems arise from an absence of adequate policies, facilitating
      legislation, and an environmentally enthused public, which therefore have a
      negative impact on the environment and health. Solid waste generation in Zarqa
      Governorate has increased exponentially and has polluted natural resources and
      the environment. A significant change in municipal solid waste generation was
      evident between the years 1994 and 2000. The Zarqa Governorate generated 482
      tons/day in 2002 with a per capita rate of 0.44 kg/cap-day [Consulting Engineers,
      2002, Feasibility study for the treatment of industrial wastewater in Zarqa
      Governorate. A project funded by METAP and Zarqa Chamber of Industry. Unpublished
      report]. This manuscript assesses the current operational and management
      practices of solid waste in the Zarqa Governorate; and evaluates the associated
      issues of solid waste collection, storage, transport, disposal and recycling in
      developing countries. The lack of techniques, financial funds and awareness among
      public and private sectors form an obstacle for achieving a successful
      environmental program. Several options are proposed to address management goals.
      Although Jordan became the first country in the Middle East to adopt a national
      environmental strategy; waste disposal is still largely uncontrolled and large
      quantities of waste go uncollected. Ensuring proper management of solid wastes,
      enforcing regulations, and implementing proper environmental awareness programs
      that will enhance the public understanding and achieve greater efficiency, are
      the findings of this study.

PMID- 16112563
TI  - Pretreatment of municipal solid waste prior to landfilling.
AB  - An outdoor pilot-scale study was undertaken to pretreat municipal solid waste by
      windrow composting. The raw waste was introduced to active composting without any
      source separation or pulverization. Pretreatment indicators were developed and
      used as a tool to measure the optimum level of sorting and waste stabilization.
      The moisture content of the waste dropped from 68% to 61% and the pile attained a
      thermophilic temperature in one week. It was observed that the C/N ratio, pH
      profile and temperature gradients were comparable to that of traditional windrow
      composting. Within one week of active bulk composting, the easily degradable
      organic matter was consumed and there was a significant reduction in the bulk
      volume of the mixed waste. The pre-composted wastes were then sorted into four
      fractions. Compared to the initial untreated waste, the pretreated waste showed
      greater sorting efficiency and reduced volatile solids. A 1-m(3) cage was used to
      study pile settlement and volume reduction. The results indicate that
      pretreatment by bulk composting could reduce by approximately 40% the total mass
      of waste hauled to landfill sites in developing countries.

PMID- 16112564
TI  - Imaging spectroscopy based strategies for ceramic glass contaminants removal in
      glass recycling.
AB  - The presence of ceramic glass contaminants in glass recycling plants reduces
      production quality and increases production costs. The problem of ceramic glass
      inspection is related to the fact that its detectable physical and pictorial
      properties are quite similar to those of glass. As a consequence, at the sorting
      plant scale, ceramic glass looks like normal glass and is detectable only by
      specialized personnel. In this paper an innovative approach for ceramic glass
      recognition, based on imaging spectroscopy, is proposed and investigated. In
      order to define suitable inspection strategies for the separation between useful
      (glass) and polluting (ceramic glass) materials, reference samples of glass and
      ceramic glass presenting different colors, thicknesses, shapes and manufacturing
      processes have been selected. Reflectance spectra have been obtained using two
      equipment covering the visible and near infrared wavelength ranges (400-1000 and
      1000-1700 nm). Results showed as recognition of glass and ceramic glass is
      possible using selected wavelength ratios, in both visible and near infrared
      fields.

PMID- 16112565
TI  - Research on solid waste management system: to improve existing situation in Corlu
      Town of Turkey.
AB  - Over the past decades, uncontrolled population growth and rapid urbanization and
      industrialization have resulted in environmental problems in Corlu Town, Turkey.
      One of the most important problems is solid waste due to inadequate management
      practices. Nowadays, increasing public awareness of the environment compels local
      authorities to define and to adopt new solutions for waste management. This paper
      presents a general overview of current solid waste management practices in Corlu
      Town and principles of the recommended municipal solid waste (MSW) management
      system. In Corlu, 170 tonnes of municipal solid waste are generated each day, or
      1.150 kg per capita per day. Approximately one-half of the municipal solid waste
      generated is organic material and 30% of the MSW consists of recyclable
      materials. The recommended system deals with maximizing recycling and minimizing
      landfilling of municipal solid waste, and consists of separation at source,
      collection, sorting, recycling, composting and sanitary landfilling. This study
      also analyzed the recommended system with respect to feasibility and economics.
      To evaluate whether the suggested system is cost effective or not, the operating
      cost of the recommended system and market prices of recyclable materials were
      compared, and the results show that the recommended system will reduce required
      landfill volume up to 27% of compared to the present situation. The profit of the
      recommended system is estimated to be about 80 million US dollars.

PMID- 16112567
TI  - Chemoprevention in lung carcinogenesis--an overview.
AB  - Lung cancer ranks among the most commonly occurring malignancies and is currently
      the leading cause of cancer-related death worldwide. This is due to its late
      diagnosis and relative resistance to standard oncological treatment approaches.
      The heavy burden of lung cancer and its treatment resistance have elicited an
      intense interest in the promising approach of chemoprevention. Chemoprevention is
      defined as a pharmacologic intervention to suppress or reverse the carcinogenic
      process and the lung is one of the most studied sites for cancer chemoprevention.
      This review, with a short update on pulmonary carcinogenesis, will summarize the
      available knowledge of chemoprevention trials and agents with a preventive
      potential in the 'lung field'.

PMID- 16112566
TI  - Dual polarisation interferometry characterisation of DNA immobilisation and
      hybridisation detection on a silanised support.
AB  - Dual polarisation interferometry is an analytical technique that allows the
      simultaneous determination of thickness, density and mass of a biological layer
      on a sensing waveguide surface in real time. We evaluated, for the first time,
      the ability of this technique to characterise the covalent immobilisation of
      single stranded probe DNA and the selective detection of target DNA hybridisation
      on a silanised support. Two immobilisation strategies have been evaluated: direct
      attachment of the probe molecule and a more complex chemistry employing a 1,2
      homobifunctional crosslinker molecule. With this technique we demonstrate it was
      possible to determine probe orientation and measure probe coverage at different
      stages of the immobilisation process in real time and in a single experiment. In
      addition, by measuring simultaneously changes in thickness and density of the
      probe layer upon hybridisation of target DNA, it was possible to directly
      elucidate the impact that probe mobility had on hybridisation efficiency. Direct
      covalent attachment of an amine modified 19 mer resulted in a thickness change of
      0.68 nm that was consistent with multipoint attachment of the probe molecule to
      the surface. Blocking with BSA formed a dense layer of protein molecules that
      absorbed between the probe molecules on the surface. The observed hybridisation
      efficiency to target DNA was approximately 35%. No further significant
      reorientation of the probe molecule occurred upon hybridisation. The initial
      thickness of the probe layer upon attachment to the crosslinker molecule was 0.5
      nm. Significant reorientation of the probe molecule surface normal occurred upon
      hybridisation to target DNA. This indicated that the probe molecule had greater
      mobility to hybridise to target DNA. The observed hybridisation efficiency for
      target DNA was approximately 85%. The results show that a probe molecule attached
      to the surface via a crosslinker group is better able to hybridise to target DNA
      due to its greater mobility.

PMID- 16112568
TI  - Biosorption of copper(II) and cobalt(II) from aqueous solutions by crab shell
      particles.
AB  - Biosorption of each of the heavy metals, copper(II) and cobalt(II) by crab shell
      was investigated in this study. The biosorption capacities of crab shell for
      copper and cobalt were studied at different particle sizes (0.456-1.117 mm),
      biosorbent dosages (1-10 g/l), initial metal concentrations (500-2000 mg/l) and
      solution pH values (3.5-6) in batch mode. At optimum particle size (0.767 mm),
      biosorbent dosage (5 g/l) and initial solution pH (pH 6); crab shell recorded
      maximum copper and cobalt uptakes of 243.9 and 322.6 mg/g, respectively,
      according to Langmuir model. The kinetic data obtained at different initial metal
      concentrations indicated that biosorption rate was fast and most of the process
      was completed within 2h, followed by slow attainment of equilibrium. Pseudo
      second order model fitted the data well with very high correlation coefficients
      (>0.998). The presence of light and heavy metal ions influenced the copper and
      cobalt uptake potential of crab shell. Among several eluting agents, EDTA (pH
      3.5, in HCl) performed well and also caused low biosorbent damage. The biosorbent
      was successfully regenerated and reused for five cycles.

PMID- 16112569
TI  - Heavy metal removal from aqueous solution by wasted biomass from a combined AS
      biofilm process.
AB  - This study evaluated the capability of metal biosorption by wasted biomass from a
      combined anaerobic-anoxic-oxic (A2O)-biofilm process with simultaneous nitrogen
      and phosphorus removal. Zinc, cadmium and nickel were rapidly adsorbed in 20 min
      by the harvested sludge from a continuous-flow pilot-plant. Biosorption
      equilibrium was then reached in 6h. The biosorption isotherm showed that metal
      biosorption behavior had fitted well to the Freundlich isotherm, but not Langmuir
      isotherm. The capacity constants k of Freundlich model for nickel, zinc and
      cadmium were 0.471, 0.298 and 0.726, respectively; the affinity constants 1/n
      were 0.444, 0.722 and 0.718, respectively. The order of metal affinity for the
      wasted biomass was Zn > Cd > Ni, which was in conformity to the other biosorption
      results with different biological sludge.

PMID- 16112570
TI  - Influence of carbon and buffer amendment on ammonia volatilization in composting.
AB  - Laboratory-scale experiments were carried out to test a mathematical model of the
      nitrogen dynamics in a composting process. The main ingredients of composting
      materials were wheat straw and dairy manure. The influence of (a) two carbon
      amendments, i.e. molasses and office paper, and (b) two chemicals forming buffer
      solutions on ammonia volatilization were investigated. Nitrogen losses amounted
      to 12-25% of initial nitrogen, in which ammonia volatilization accounted for 60
      99%. Addition of molasses, a readily available form of carbon, reduced cumulative
      ammonia emissions substantially, but office paper, i.e. cellulose, had only a
      small influence. The addition of buffering chemicals did not significantly reduce
      ammonia volatilization.

PMID- 16112571
TI  - Trifluoromethyl group as a pharmacophore: effect of replacing a CF3 group on
      binding and agonist activity of a glucocorticoid receptor ligand.
AB  - Compound 1, a potent glucocorticoid receptor ligand, contains a quaternary carbon
      bearing trifluoromethyl and hydroxyl groups. This paper describes the effect of
      replacing the trifluoromethyl group on binding and agonist activity of the GR
      ligand 1. The results illustrate that replacing the CF3 group with a
      cyclohexylmethyl or benzyl group maintains the GR binding potency. These
      substitutions alter the functional behavior of the GR ligands from agonists to
      antagonists. Docking studies suggest that the benzyl analog 19 binds in a similar
      fashion as the GR antagonist, RU486. The central benzyl group of 19 and the C-11
      dimethylaniline moiety of RU486 overlay. Binding of compound 19 is believed to
      force helix 12 to adopt an open conformation and this leads to the antagonist
      properties of the non-CF3 ligands carrying a large group at the center of the
      molecule.

PMID- 16112572
TI  - Emergency care for people with learning disabilities: what all nurses and
      midwives need to know.
AB  - People with learning disabilities have high health needs and as a result will
      require access to all aspects of healthcare systems, including the emergency
      services. The evidence of the health needs experienced by this group is evolving
      and developing and they have a range of issues that will bring them into contact
      with general hospital and the emergency services. It is now apparent that they
      experience risks to their health when accessing general hospital care and action
      is required to identify and address their distinct health needs. Emergency
      services are often the first point of entry into the healthcare system and as a
      result they need to develop their knowledge and skills in meeting the health
      needs of this group. Partnership working with specialists in learning disability
      health and emergency care can help to improve care.

PMID- 16112573
TI  - Intersegmental dynamics during the swing phase of gait: a comparison of knee
      kinetics between 7 year-old children and adults.
AB  - Existing literature suggests that kinetic patterns associated with children's
      gait may not be adult-like until after 7 years of age. The development of adult
      like kinetic patterns, especially those involving non-muscular interaction
      moments, occurs with time and experience. We tested the hypothesis that compared
      to adults, 7 year-old children would demonstrate a relatively larger contribution
      of muscle moment and a smaller contribution of interaction moment to the net knee
      joint moment during the swing phase of gait was tested. Net knee joint moments
      and the contributions of muscle and interaction moments to the net moments were
      compared between 7 year-old children and adults. Knee kinematics and net joint
      moments were similar between the two groups. Also, the contributions of the
      muscle and interaction moments to the net joint moment were similar (P > 0.05),
      suggesting that the ability to employ interaction moments during the swing phase
      of gait did not differ between the two groups.

PMID- 16112574
TI  - A 3D active shape model for the evaluation of the alignment of the spine during
      sleeping.
AB  - This paper explains how the shape of the spine can be evaluated from back surface
      measurements in a recumbent position, by using point distribution models (PDM)
      and typical shape variability of the spine in a lateral sleeping position. CT
      scans of 12 volunteers were taken in this posture on a firm and a soft sleeping
      system to provide a training set for the PDM. Active shape models (ASM) were used
      to enhance the accuracy of the spinal reconstruction from measurements by
      limiting the shape of the spine to characteristic shapes from a biomechanical
      and/or clinical point of view. A comparison was made between calculated shapes,
      obtained from surface measurements, and those measured vertebral body centres
      (from CT-scans). An RMS accuracy of 2.6mm was obtained in 3D, and 1.8mm in
      frontal view, which was sufficient to compare spinal deformations of a subject on
      different sleeping systems.

PMID- 16112575
TI  - Relationship between hamstring activation rate and heel contact velocity: factors
      influencing age-related slip-induced falls.
AB  - The purpose of this research was to determine whether a decreased hamstring
      activation rate among the elderly is responsible for a higher horizontal heel
      contact velocity and increased likelihood of slip-induced falls compared to their
      younger counterparts. Twenty-eight subjects from two age groups (14 young and 14
      old) walked across a linear walking track with embedded force platforms while
      wearing a fall arresting harness attached to an overhead arresting rig for
      safety. In order to obtain realistic unexpected slip-induced fall data, a soapy
      vinyl floor surface was hidden from the subjects and unexpectedly introduced.
      Synchronized kinematics, kinetic and electromyography (EMG) analyses during the
      heel contact phase of the gait cycle while walking over slippery and non-slippery
      floor surfaces were examined in the study. Normalized EMG data were examined in
      terms of hamstring activation rate and evaluated with heel contact velocity and
      friction demand characteristic (as measured by peak required coefficient of
      friction (RCOF)) on the dry vinyl floor surface. Furthermore, slip parameters
      (i.e. slip distances and slipping velocity) were assessed on the soapy vinyl
      floor surface. The results indicated that younger adults' hamstring activation
      rate was higher than older adults, whereas younger adults' heel contact velocity
      was not different from older adults. These results suggested that heel contact
      velocity in younger adults was sufficiently reduced before the heel contact phase
      of the gait cycle. This could be due to the outcome of higher hamstring
      activation rate in younger adults in comparison to older adults. However, lower
      friction demand (peak RCOF), shorter slip distances, slower peak sliding heel
      velocity and more falls among older adults suggested that the slip initiation
      characteristics were not the only factors contributing to slip-induced falls
      among the elderly.

PMID- 16112576
TI  - Comparison of 3D joint moments using local and global inverse dynamics approaches
      among three different age groups.
AB  - A complete understanding of joint moment is important to locomotion research. The
      purpose of the study was to compare stance phase lower extremity joint moments,
      calculated by a three-dimensional (3D) inverse dynamics model and expressed in
      global and local coordinate systems, to examine the influence of different
      coordinate systems on joint moment profiles. Additionally, aging influences on
      joint moments were examined. Thirty healthy (10 young, 10 middle-aged and 10 old)
      participants were involved in the current study. Kinematic and kinetic data were
      collected using standard gait study protocol. Results suggested that globally
      expressed joint moments were significantly different than those expressed
      locally. Furthermore, significant moment differences were found between young and
      old age groups. The older adults produced less evertor muscle moments at the
      ankle joint. However, aging effect was not significant for majority of the joint
      moment comparisons. It is concluded that coordinate system need to be carefully
      chosen, and specified in 3D joint moment analysis, while significant error
      introduced by using 2D analysis need to be considered.

PMID- 16112577
TI  - Cell individuality: the bistability of competence development.
AB  - Heterogeneous development of competence among cells of the bacterium Bacillus
      subtilis provides an appealing model of cell individuality, an area that is
      currently attracting considerable research interest. Under appropriate
      conditions, only a fraction of cells in an isogenic culture become competent for
      transformation. Two experimental studies have now pinpointed the same auto
      stimulatory feedback loop of gene expression as the principal requirement for the
      establishment of this 'bistable' response.

PMID- 16112578
TI  - 100th anniversary of Robert Koch's Nobel Prize for the discovery of the tubercle
      bacillus.
AB  - The year 2005 marks the 100th anniversary of Robert Koch's Nobel Prize. Here, we
      describe the scientific career of Robert Koch, the discoverer of the etiologic
      agent of tuberculosis but also of those of anthrax, cholera and wound infections.
      Equally important, Koch developed the methodologies and concepts that made
      medical microbiology a scientific discipline. Despite great efforts, however,
      Koch failed to conquer tuberculosis, which still causes enormous health problems
      worldwide 100 years after his Nobel award.

PMID- 16112579
TI  - Xanthones induce cell-cycle arrest and apoptosis in human colon cancer DLD-1
      cells.
AB  - We investigated the antiproliferative effects of four structurally similar
      prenylated xanthones, alpha-mangostin, beta-mangostin, gamma-mangostin, and
      methoxy-beta-mangostin, in human colon cancer DLD-1 cells. These xanthones differ
      in the number of hydroxyl and methoxy groups. Except for methoxy-beta-mangostin,
      the other three xanthones strongly inhibited cell growth at 20 microM and their
      antitumor efficacy was correlated with the number of hydroxyl groups. Hoechst
      33342 nuclear staining and nucleosomal DNA-gel electrophoresis revealed that the
      antiproliferative effects of alpha- and gamma-mangostin, but not that of beta
      mangostin, were associated with apoptosis. It was also shown that their
      antiproliferative effects were associated with cell-cycle arrest by affecting the
      expression of cyclins, cdc2, and p27; G1 arrest was by alpha-mangostin and beta
      mangostin, and S arrest by gamma-mangostin. These findings provide a relevant
      basis for the development of xanthones as an agent for cancer prevention and
      combination therapy with anti-cancer drugs.

PMID- 16112580
TI  - Homology modelling and active-site-mutagenesis study of the catalytic domain of
      the pneumococcal phosphorylcholine esterase.
AB  - Streptococcus pneumoniae is among the major human pathogens. Several interactions
      of this bacterium with its host appear to have been mediated by bacterial cell
      wall components. Specifically, phosphorylcholine residues covalently attached to
      teichoic and lipoteichoic acids serve as anchors for many surface-located
      proteins (choline-binding proteins CBPs), including cell-adhesion and virulence
      factors, and are also recognized by host response components through choline
      binding receptors. In this study, we have performed modelling of the catalytic
      domain of pneumococcal phosphorylcholine esterase (Pce), a modular enzyme that is
      capable of removing phosphorycholine residues from teichoic and lipoteichoic
      acids, remodelling their distribution on the bacterial envelope. We wish to
      contribute to the structural knowledge of Pce. In this pursuit, 3D models of Pce
      have been established by homology modelling, using the X-ray structure of enzymes
      from the alpha/beta metallo-lactamase family fold as templates. Theoretical
      models of pneumococcal phosphorylcholine esterase (Pce) catalytic modules
      obtained by homology modelling, and corresponding docking studies employed to
      find out the residues involved in the binding of Zn ions, are discussed according
      to mutational studies and ab initio calculations. The presence of a binuclear Zn
      cluster in the catalytic domain of Pce and a likely coordination model are
      proposed.

PMID- 16112581
TI  - Methyltrioxorhenium catalysed synthesis of highly oxidised aryltetralin lignans
      with anti-topoisomerase II and apoptogenic activities.
AB  - A novel and efficient procedure to prepare highly oxidised aryltetralin lignans,
      such as isopodophyllotoxone and (-)-aristologone derivatives, by oxidation of
      podophyllotoxin and galbulin with methylrhenium trioxide (MTO) and novel MTO
      heterogeneous catalysts is reported. It is noteworthy that in the case of
      isopodophyllotoxone derivatives the functionalisation of the C-4 position of the
      C-ring and the ring-opening of the D-lactone moiety increased the activity
      against topoisomerase II while causing the undesired inhibition of tubulin
      polymerisation to disappear. The novel (-)-aristologone derivatives showed
      apoptogenic activity against resistant human lymphoma cell lines.

PMID- 16112582
TI  - Synthesis and biological evaluation of polyhydroxycurcuminoids.
AB  - A series of curcumin analogs (1-3, 5a-5t) was synthesized through the
      condensation of appropriately protected hydroxybenzaldehydes with acetylacetone,
      followed by deprotection. The antioxidant activity of these analogs was
      determined by superoxide free radical nitroblue tetrazolium and DPPH free radical
      scavenging methods and the polyhydroxycurcuminoids (5l-5s) displayed excellent
      antioxidant activity. These analogs showed cytotoxicity to lymphocytes and
      promising tumor-reducing activity on Dalton's lymphoma ascites tumor cells.

PMID- 16112583
TI  - Aza-bicyclic amino acid carboxamides as alpha4beta1/alpha4beta7 integrin receptor
      antagonists.
AB  - A series of N-carboxy, N-alkyl, and N-carboxamido azabicyclo[2.2.2]octane
      carboxamides were prepared and assayed for inhibition of alpha4beta1-VCAM-1 and
      alpha4beta7-MAdCAM-1 interactions. Potency and alpha4beta1/alpha4beta7
      selectivity were sensitive to the substituent R1-R3 in the structures 6, 7, and
      8. Several compounds demonstrated low nanomolar balanced alpha4beta1/alpha4beta7
      in vitro activity. Two compounds were selected for in vivo leukocytosis studies
      and demonstrated increases in circulating lymphocytes up to 250% over control.

PMID- 16112585
TI  - Enhanced expressions of endometrial tumour necrosis factor alpha and its
      receptors during early pregnancy in bonnet monkeys.
AB  - Tumour necrosis factor alpha (TNF-alpha), a pro-inflammatory cytokine may play an
      active role in stimulating inflammatory reactions during pregnancy. However, the
      expression of endometrial TNF-alpha has not been investigated especially during
      early pregnancy, a phenomenon invariably accompanied by inflammatory reaction. In
      the present study, the endometrial expressions of TNF-alpha and its receptors
      (TNFR1 and TNFR2) during early pregnancy, when the embryo lies free in the zona
      hatched state in the uterine lumen, were analyzed by immunohistochemistry. The
      endometrial expressions of TNF-alpha, TNFR1 and TNFR2 were found to be
      significantly up-regulated (p < 0.05) in the glandular epithelium on day 6 post
      ovulation in pregnant animals. The alteration in the expression of these
      molecules may contribute to the induction of local inflammatory reactions during
      implantation.

PMID- 16112584
TI  - Electroporation of transplantable tumour for the enhanced accumulation of
      photosensitizers.
AB  - The aim of this study was to verify whether electroporation could increase the
      accumulation of the hydrophilic photosensitizers: aluminium phthalocyanine
      tetrasulphonate (AlPcS(4)) and chlorin e(6) (C e(6)) in tumour tissue. The
      experiment was performed in vivo using hybrid mice (C57Bl/CBA) bearing hepatoma
      A22 (MH-A22) tumours transplanted in the right haunch. The time dependence of the
      fluorescence intensity of administered photosensitizers was measured after the
      ordinary and electrically stimulated delivery. The obtained fluorescence
      spectroscopy results implied the tumour being affected by an electrical field in
      a way, which led to a higher accumulation of both photosensitizers (AlPcS(4) and
      C e(6)) in the periphery of the tumour and it superficial layer. Our pilot study
      suggests that electroporation could be considered as a useful procedure seeking
      for the more effective application of photodynamic tumour treatment.

PMID- 16112586
TI  - Principles, processes, and puzzles of social cognition: an introduction for the
      special issue on social cognitive neuroscience.
AB  - This article introduces the special issue of NeuroImage focused on social
      cognitive neuroscience. Social psychology has a rich history of making sense of
      the often paradoxical aspects of social cognition and the social world. This
      article reviews the principles, processes, and puzzles of social cognition and
      behavior that have been examined by social psychologists for decades. Five
      principles of social cognition and behavior are reviewed including: (1) the power
      of the situation over behavior, (2) blindness for situational influences, (3)
      social perception and self-perception are constructive processes, (4) blindness
      for the constructed nature of social and self-perception, and (5) self-processes
      are social. Four processes of social cognition are reviewed including: (1)
      cognitive architecture; (2) automaticity and control; (3) motivated reasoning;
      and (4) accessibility, frames, and expectations. Finally, five areas of social
      cognition that contain enduring puzzles are described including (1) the self, (2)
      attitudes, (3) reflective social cognition, (4) automatic social cognition, and
      (5) social motives. In several of the areas of study reviewed, cognitive
      neuroscience is well positioned to make important contributions to these research
      traditions either by allowing for new tests of hypotheses or by allowing for
      unobtrusive measurement of social cognitive processes.

PMID- 16112587
TI  - Striatal D2 receptor binding as a marker of prognosis and outcome in untreated
      first-episode psychosis.
AB  - In a preliminary 123I-IBZM SPECT study in first-episode psychosis, a relationship
      between striatal dopaminergic D2 receptor (D2R) binding and premorbid adjustment
      was suggested. These results were replicated in the present study (n = 18), and
      D2R binding at diagnosis predicted a high probability for schizophrenia outcome
      by 2-year follow-up. The present findings contribute to the evidence of abnormal
      D2R binding in schizophrenia and suggest that SPECT might be useful for outcome
      prediction in first-episode psychosis.

PMID- 16112588
TI  - Lamotrigine suppresses neurophysiological responses to somatosensory stimulation
      in the rodent.
AB  - Neurotransmitter release and voltage-gated ion channel activity in excitatory
      neurons are critical for understanding and interpreting neuroimaging signals.
      Couplings between changes in neural activity and energetic/vascular responses are
      assumed for interpretation of neuroimaging signals. To investigate involvement of
      neural events to neuroenergetic/neurovascular responses, we conducted multi-modal
      magnetic resonance imaging (MRI) measurements (at 7.0 T) and electrophysiological
      recordings (with high impedance microelectrodes) for local field potential (LFP)
      and spiking frequency (nu) in alpha-chloralose-anesthetized rats. The rats
      underwent forepaw stimulation before and after treatment of lamotrigine, a
      neuronal voltage-gated ion channel blocker and glutamate release inhibitor. Multi
      modal MRI measurements of cerebral blood flow (CBF) and blood oxygenation level
      dependent (BOLD) signal were combined to estimate changes in cerebral metabolic
      rate of oxygen consumption (CMRo2). Lamotrigine did not appreciably affect values
      of nu, CBF, and CMRo2 in the resting state. After lamotrigine treatment, evoked
      changes in LFP and nu were attenuated, which were consistent with commensurate
      declines in deltaCBF and deltaCMRo2. While number of evoked BOLD-activated voxels
      was considerably reduced with lamotrigine, intensities of voxels in middle
      cortical layers were affected to a lesser degree by lamotrigine. The results
      suggest that lamotrigine suppresses evoked neurophysiological (i.e.,
      neural/energetic/vascular) responses, both in terms of volume of tissue activated
      and degree of activation in the foci. Since lamotrigine affects evoked responses
      but not the basal signals, it can be suggested that glutamate release and
      activity of voltage-gated ion channels are essential for initiating evoked
      energetic/vascular responses, and thereby important for interpretation of
      incremental changes in neuroimaging signal.

PMID- 16112589
TI  - Simultaneous recording of laser-evoked brain potentials and continuous, high
      field functional magnetic resonance imaging in humans.
AB  - Simultaneous recording of event-related electroencephalographic (EEG) and
      functional magnetic resonance imaging (fMRI) responses has the potential to
      provide information on how the human brain reacts to an external stimulus with
      unique spatial and temporal resolution. However, in most studies combining the
      two techniques, the acquisition of functional MR images has been interleaved with
      the recording of evoked potentials. In this study we investigated the feasibility
      of recording pain-related evoked potentials during continuous and simultaneous
      collection of blood oxygen level-dependent (BOLD) functional MR images at 3 T.
      Brain potentials were elicited by selective stimulation of cutaneous Adelta and C
      nociceptors using brief radiant laser pulses (laser-evoked potentials, LEPs). MR
      induced artifacts on EEG data were removed using a novel algorithm. Latencies,
      amplitudes, and scalp distribution of LEPs recorded during fMRI were not
      significantly different from those recorded in a control session outside of the
      MR scanner using the same equipment and experimental design. Stability tests
      confirmed that MR-image quality was not impaired by the evoked potential
      recording, beyond signal loss related to magnetic susceptibility differences
      local to the electrodes. fMRI results were consistent with our previous studies
      of brain activity in response to nociceptive stimulation. These results
      demonstrate the feasibility of recording reliable pain-related LEPs and fMRI
      responses simultaneously. Because LEPs collected during fMRI and those collected
      in a control session show remarkable similarity, for many experimental designs
      the integration of LEP and fMRI data collected in separate, single-modality
      acquisitions may be appropriate. Truly simultaneous recording of LEPs and fMRI is
      still desirable in specific experimental conditions, such as single-trial,
      learning, and pharmacological studies.

PMID- 16112590
TI  - A high-performance liquid chromatographic assay for determination of cisplatin in
      plasma, cancer cell, and tumor samples.
AB  - A method for determination of cis-diaminedichloroplatinum (II) (cisplatin) in
      ultrafiltered plasma, cell, and tumour samples is described. Cisplatin separation
      was carried out on a reversed-phase column using methanol-acetonitrile-water as
      the mobile phase. The flow rate was maintained constant at 1.6 mL/min and
      analysis was performed at 23 degrees C. Detection was carried out by absorbance
      at 254 nm. The method was linear in the range of 0.2-10 microg/mL, and the
      coefficients of variation were <10%. Using this technique, we measured the
      intracellular accumulation of cisplatin in cancer cells and in tumours of mice
      receiving treatment with cisplatin and evaluated the pharmacokinetics of
      cisplatin in nu/nu mice after intraperitoneal (i.p.) administration. The method
      proved to be adequate for measuring cisplatin both in vitro and in vivo and could
      be suitable for studies of cisplatin pharmacokinetics in animal models.

PMID- 16112591
TI  - A closed system for the clinical banking of umbilical cord blood.
AB  - Umbilical cord blood (UCB) is a source of hematopoietic progenitor cells and is
      used as an alternative to the bone marrow or peripheral blood for treatment of
      several onco-hematological diseases. Because of the limited number of CD34+
      hematopoietic stem cells present in UCB units and of the elevated costs of
      cryopreservation, it is of paramount importance to select the UCB units that are
      clinically useful before storage and optimize banking efficiency by designing
      reliable procedures to process and freeze the selected units. Among the different
      parameters characterizing UCB, nucleated cell (NC) and CD34+ cell content
      provides useful criteria to select UCB units since clinical data documented that
      the infused cell load (both NC and CD34+ cells) plays an important role in the
      successful outcome of transplants. By evaluating volume, CD34+ cell content, NC
      total amount, and NC density of 117 UCB units, we found a significant association
      between CD34+ cell content and NC density and total amount, indicating these
      parameters as useful to decide UCB clinical utility. Furthermore, we set up a
      fast procedure to process UCB units for storage. A system for NC separation and
      volume reduction of UCB samples in a dedicated, germ-free, closed circuit was
      developed, where plasma and red blood cells (RBC) depletion was obtained by
      sedimentation in the presence of a 3.5% Polygeline solution. By this separation
      system, both RBC depletion and high NC and CD34+ cell recoveries were achieved in
      60 min, and the yield was comparable to the one obtained by other separation
      methods. Since Polygeline has been clinically used as a plasma expander and no
      toxic effects on patients were reported, the protocol can be applied in the large
      scale banking of UCB.

PMID- 16112592
TI  - Influence of the crosstalk between growth hormone and insulin signalling on the
      modulation of insulin sensitivity.
AB  - Growth hormone (GH) is an important modulator of insulin sensitivity. Multiple
      mechanisms appear to be involved in this modulatory effect. GH does not interact
      directly with the insulin receptor (IR), but conditions of GH excess are
      associated in general with hyperinsulinemia that induces a reduction of IR levels
      and impairment of its kinase activity. Several post-receptor events are shared
      between GH and insulin. This signaling crosstalk could be involved in the
      diabetogenic effects of GH. The utilization of animal models of GH excess,
      deficiency or resistance provided evidence that the signaling pathway leading to
      stimulation of the phosphatidylinositol 3-kinase (PI3K)/Akt cascade is an
      important site of regulation, and pointed to the liver as the major site of GH
      induced insulin resistance. In skeletal muscle, GH-induced insulin resistance
      might involve an increase in the amount of the p85 subunit of PI3K that plays a
      negative role in insulin signalling. GH also reduces insulin sensitivity by
      enhancing events that negatively modulate insulin signaling such as stimulation
      of serine phosphorylation of IRS-1, which prevents its recruitment to the IR and
      induction of the suppressor of cytokine signalling (SOCS)-1 and SOCS-3 which
      modulate the signalling potential of the IRS proteins. In addition, GH has been
      shown to decrease the expression of the insulin-sensitizing adipo-cytokines
      adiponectin and visfatin. Finally, genetic manipulation of mice indicated that
      whereas GH plays a major role in reducing insulin sensitivity, circulating IGF-I
      also participates in the control of insulin sensitivity and plays an important
      role in the hormonal balance between GH and insulin.

PMID- 16112593
TI  - Multiple myelomas in cats.
AB  - Multiple myelomas are uncommon neoplasms of the bone marrow of cats [Weber NA,
      Tebeau CS (1998) An unusual presentation of multiple myeloma in two cats. Journal
      of the American Animal Hospital Association34 (6), 477-483]. Nine cats diagnosed
      with multiple myelomas were retrospectively identified over a 16-year period
      (1986-2002). Cats with multiple myelomas were older than 7 years (mean age 11.7
      years); six males and three females were affected (2.1), but no breed
      predisposition was evident. Treatment of multiple myelomas consisted of
      supportive management in the nine cats and anti-neoplastic therapy in eight cats.
      Supportive treatment consisted of maintaining hydration, renal function and
      antimicrobial therapy even when there was no sign of infection. Anti-neoplastic
      therapy with melphalan and prednisolone was carried out in eight cats. Three
      failed to respond to treatment and five responded to treatment, but the response
      was only partial and temporary in one cat. The five cats that responded were
      improved clinically and had reduced serum protein levels. Five out of eight cats
      (63%) responded to chemotherapy, and it appeared to be complete in four cats and
      partial in one cat. Survival time in those cats was 15, 4, 17 and 24 months.

PMID- 16112594
TI  - Osteoporosis and Crohn's disease.
AB  - Osteoporosis and osteopenia have been reported frequently in patients with
      inflammatory bowel disease, most notably Crohn's disease. OBJECTIVES: To
      determine the prevalence and risk factors of osteoporosis in patients with
      Crohn's disease. METHODS: Prospective study of 56 patients with Crohn's disease,
      34 men and 22 women with a mean age of 32 +/- 10.4 years (18-54 years) and no
      history of disorders known to influence bone metabolism. Dual-energy X-ray
      absorptiometry measurements of bone mineral density (BMD) were obtained at the
      femoral neck and lumbar spine. A multivariate model including those factors
      significantly associated with low BMD in the univariate analysis was used to
      identify independent risk factors. RESULTS: Osteoporosis was found in 35.7% and
      osteopenia in 23.2% of patients. Low BMD was significantly associated with low
      body mass index (BMI), colonic involvement, and glucocorticoid therapy. Low BMI
      was an independent risk factor for low BMD. Malnutrition with BMI < or =18 kg/m2
      was noted in 21 patients, of whom 76.2% had low BMD values, as compared to 48.6%
      of the patients whose BMI was >18 kg/m2 (P = 0.03, odds ratio = 3.4). CONCLUSION:
      Among risk factors for bone loss in patients with Crohn's disease, malnutrition
      plays a prominent role that deserves attention when planning treatment programs.

PMID- 16112595
TI  - Acquired hypophosphatemic osteomalacia associated with multiple myeloma.
AB  - Hypophosphatemic osteomalacia is a rare but important complication of multiple
      myeloma. In these cases, the pathophysiology of the phosphate renal wasting
      notably differs from oncogenic osteomalacia and is due to light-chain
      nephropathy, resulting in proximal tubular dysfunction which is not restricted to
      phosphate handling. These patients seems to have a distinct type of plasma cell
      disorder characterized by a slow progression of the tumor and by an early phase
      dominated by the metabolic complications of the renal proximal tubular
      dysfunction. For this reason hypophosphatemic osteomalacia is the presenting
      feature that leads to the diagnosis of multiple myeloma in most of these
      patients. Recognition of this complication is important, since supportive
      treatment with phosphate supplements and calcitriol may substantially alleviate
      pain and weakness associated with hypophosphatemia.

PMID- 16112596
TI  - Airborne ultrasound for the precipitation of smokes and powders and the
      destruction of foams.
AB  - Sonochemistry is generally associated with the use of power ultrasound in liquid
      media. Under such circumstances acoustic cavitation can drive a range of
      reactions and processes. The use of airborne ultrasound in processing is less
      familiar because of the difficulties that relate to the use of ultrasound in
      gaseous systems. Firstly there is a greater attenuation (power loss) in the
      transmission of sound through air compared with that through liquid. Secondly the
      transfer of acoustic energy generated in air into a liquid or solid material is
      inefficient due to the mismatch between acoustic impedances of gases and solids
      or liquids. Despite this, applications do exist for airborne ultrasound but the
      source must be very powerful and efficient. In this way one can obtain levels of
      intensities at which it is possible to use ultrasound for specific applications
      such as to agglomerate fine dusts and to break down foams.

PMID- 16112597
TI  - Reduction of compartment compliance increases venous flow pulsatility and lowers
      apparent vascular compliance: implications for cerebral blood flow hemodynamics.
AB  - The global compliance of a fixed-volume, incompressible compartment may play a
      significant role in determining the inherent vascular compliance. For the
      intracranial compartment, we propose that the free-displacement of the cerebral
      spinal fluid (CSF) directly relates to cerebral vascular compliance. To test this
      hypothesis, an in vivo surrogate intracranial compartment was made by enclosing a
      rabbit's kidney within a rigid, fluid-filled container. Opening/closing a port
      atop the box modulated the free flow of box fluid (open-box state). We observed
      that the pulsatility of the renal venous outflow increased in response to
      hampering the free flow of fluid in-and-out of the container (closed-box state).
      To associate the observed pulsatility changes with the compliance changes, a
      parametric method was proposed for the computation of the apparent compliance
      (C(app)) of the whole renal vascular system. The calculated C(app) for each
      experiment's closed-box state was favorably compared to a time-domain compliance
      assessment method at the mean heart rate. In addition, it was revealed that
      C(app) in the open-box state was greater than that in the closed-box state only
      when the calculations were performed at frequencies lower than the heart rate and
      closer to the ventilation rate. These experimental results support the concept
      that the vessel compliance of vascular systems enclosed within a rigid
      compartment is a function of the global compartment compliance.

PMID- 16112598
TI  - A prototype rehabilitation device with variable resistance and joint motion
      control.
AB  - Resistance exercise has been widely reported to have positive rehabilitation
      effects for patients with neuromuscular and orthopaedic conditions. This paper
      presents the design of a versatile rehabilitation device in the form of a
      rotating joint arm mounted on the adjustable seat that provides passive
      resistance during strength training for muscles. The resistance is supplied by a
      magnetorheological damper. Intelligent controls are developed to produce
      resistance force based on the prescription of the therapist. The device provides
      both isometric and isokinetic strength training and is reconfigurable for several
      human joints. Special consideration has been given to the human-machine
      interaction in the adaptive control algorithms that can modify the behavior of
      the device to account for strength gains or muscle fatigue.

PMID- 16112600
TI  - Computer-aided rodent carcinogenicity prediction.
AB  - The potential of the computer program PASS (Prediction Activity Spectra for
      Substances) to predict rodent carcinogenicity for chemical compounds was studied.
      PASS predicts carcinogenicity of chemical compounds on the basis of their
      structural formula and of structure-activity relationship analysis of known
      carcinogens and non-carcinogens. The data on structures and experimental results
      of 2-year carcinogenicity assays for 412 chemicals from the NTP (National
      Toxicological Program) and 1190 chemicals from the CPDB (Carcinogenic Potency
      Database) were used in our study. The predictions take into consideration
      information about species and sex of animals. For evaluation of the predictive
      accuracy we used two procedures: leave-one-out cross-validation (LOO CV) and
      leave-20%-out cross-validation. In the last case we randomly divided the studied
      data set 20 times into two subsets. The data from the first subset, containing
      80% of the compounds, were added to the PASS training set (which includes about
      46,000 compounds with about 1500 biological activity types collected during the
      last 20 years to predict biological activity spectra), the second subset with 20%
      of the compounds was used as an evaluation set. The mean accuracy of prediction
      calculated by LOO CV is about 73% for NTP compounds in the 'equivocal' category
      of carcinogenic activity and 80% for NTP compounds in the 'evidence' category of
      carcinogenicity. The mean accuracy of prediction for the CPDB database is 89.9%
      calculated by LOO CV and 63.4% calculated by leave-20%-out cross-validation.
      Influence of incorporation of species and sex data on the accuracy of
      carcinogenicity prediction was also investigated. It was shown that the accuracy
      was increased only for data on male animals.

PMID- 16112601
TI  - High-pressure freezing followed by cryosubstitution as a tool for preserving high
      quality ultrastructure and immunoreactivity in the Xenopus laevis pituitary
      gland.
AB  - Subcellular localisation of proteins and peptides yields fundamental information
      about cell functioning. Immunoelectron microscopy is a powerful tool to achieve
      this goal, but combining good tissue preservation with strong immunoreactivity is
      a great challenge in electron microscopy. We have applied a novel approach, using
      high-pressure freezing (HPF) followed by cryosubstitution, to prepare the
      pituitary gland of the amphibian Xenopus laevis for immunogold-electron
      microscopy. In this way, we investigated the subcellular distribution of brain
      derived neurotrophic factor and the amphibian neurohormone mesotocin in the
      pituitary neural lobe, and the peptide hormone alpha-melanophore-stimulating
      hormone and its protein precursor proopiomelanocortin in melanotrope cells of the
      pituitary intermediate lobe. In contrast to conventional chemical fixation
      (followed by cryosubstitution), HPF not only revealed strong immunoreactivity of
      the secretory products, but also provided excellent ultrastructural preservation
      of cell organelles, including secretory granule subtypes. We conclude that HPF
      followed by cryosubstitution provides a preparation technique of choice when both
      optimal tissue ultrastructure and strong immunoreactivity are required.

PMID- 16112599
TI  - Carcinogenic lead chromate induces DNA double-strand breaks in human lung cells.
AB  - Hexavalent chromium (Cr(VI)) is a widespread environmental contaminant and a
      known human carcinogen, generally causing bronchial cancer. Recent studies have
      shown that the particulate forms of Cr(VI) are the potent carcinogens.
      Particulate Cr(VI) is known to induce a spectrum of DNA damage such as DNA single
      strand breaks, Cr-DNA adducts, DNA-protein crosslinks and chromosomal
      aberrations. However, particulate Cr(VI)-induced DNA double strand breaks (DSBs)
      have not been reported. Thus, the aim of this study was to determine if
      particulate Cr(VI)-induces DSBs in human bronchial cells. Using the single cell
      gel electrophoresis assay (comet assay), showed that lead chromate-induced
      concentration dependent increases in DSBs with 0.1, 0.5, 1 and 5 microg/cm2 lead
      chromate inducing a 20, 50, 67 and 109% relative increase in the tail integrated
      intensity ratio, respectively. Sodium chromate at concentrations of 1, 2.5 and 5
      microM induced 38, 78 and 107% relative increase in the tail integrated intensity
      ratio, respectively. We also show that genotoxic concentrations of lead chromate
      activate the ataxia telangiectasia mutated (ATM) protein, which is thought to
      play a central role in the early stages of DSB detection and controls cellular
      responses to this damage. The H2A.X protein becomes rapidly phosphorylated on
      residue serine 139 in cells when DSBs are introduced into the DNA by ionizing
      radiation. By using immunofluorescence, we found that lead chromate-induced
      concentration-dependent increases in phosphorylated H2A.X (r-H2A.X) foci
      formation with 0.1, 0.5, 1, 5 and 10 microg/cm2 lead chromate inducing a relative
      increase in the number of cells with r-H2A.X foci formation of 43, 51, 115 and
      129%, respectively.

PMID- 16112602
TI  - The influence of Cu(II), Mg(II) on the binding of adriamycin with DNA and the
      study on their interaction mechanism.
AB  - Cu(II) and Mg(II) have different binding capacity with daunomycin, and have
      different combination mode with DNA. Selecting these two different metal ions,
      the influence of them on the binding constant of adriamycin with DNA and the
      related mechanism has been studied by using absorption and fluorescence
      spectroscopy. The result showed that Mg(II) has weaker binding capacity with the
      drug comparing Cu(II), but both Mg(II) and Cu(II) can obviously reduce the
      binding constant of DNA with the drug. Addition of Cu(II) to the drug-DNA binary
      system can cause the reduction of fluorescence in the system, but addition of
      Mg(II) to it can cause the enhancement of fluorescence in some conditions. This
      show that the influence of Cu(II) and Mg(II) on the binding of the drug with DNA
      may be by a different mechanism. According to the main function of Mg(II) to bind
      with the phosphate groups on DNA, it can be deduced that for the interaction of
      the aglycon portion of the drug into the base pairs of DNA, the electrostatic
      binding between amine group of the drug with the phosphate group on DNA is a
      prerequisite.

PMID- 16112603
TI  - Mass, EPR, IR and electronic spectroscopic studies on newly synthesized
      macrocyclic ligand and its transition metal complexes.
AB  - Manganese(II), cobalt(II), nickel(II) and copper(II) complexes have been
      synthesized with a new tetradentate ligand viz. 1,3,7,9-tetraaza-2,4,8,10
      tetraketo-6,12-diphenyl-cyclododecane (L) and characterized by the elemental
      analysis, molar conductance measurements, magnetic susceptibility measurements,
      mass, 1H NMR, IR, electronic and EPR spectral studies. The molar conductance
      measurements of the complexes in DMF correspond to be nonelectrolytic nature for
      Mn(II), Co(II) and Cu(II) while 1:2 electrolytes for Ni(II) complexes. Thus,
      these complexes may be formulated as [M(L)X2] and [Ni(L)]X2 (where M=Mn(II),
      Co(II) and Cu(II) and X=Cl- and NO3-). On the basis of IR, electronic and EPR
      spectral studies an octahedral geometry has been assigned for Mn(II) and Co(II)
      complexes, square-planar for Ni(II) whereas tetragonal for Cu(II) complexes. The
      ligand and its complexes were also evaluated against the growth of bacteria and
      pathogenic fungi in vitro.

PMID- 16112604
TI  - Comparative study of the H-bond and FTIR spectra between 2,2-hydroxymethyl
      propionic acid and 2,2-hydroxymethyl butanoic acid.
AB  - In the present paper, the FTIR band and H-bond differences between the two
      dihydroxy-based carboxyls, 2,2-hydroxymethyl butanoic acid (hereinafter
      abbreviated to DMBA) and 2,2-hydroxymethyl propionic acid (hereinafter
      abbreviated to DMPA), were analyzed based on the crystal structure as well as the
      relation between H-bond and FTIR band of DMPA. In addition, the energy and length
      of the H-bonds formed between COOH, between OH, between COOH and OH were also
      calculated via molecular modeling. The results showed that three H-bond types
      existing in DMPA while only two in DMBA. The COOH pattern and H-bond type in DMBA
      and DMPA can be preliminarily judged according to the band position and relative
      strength of the nuOH and nuCOOH in FTIR spectrum. The H atom in COOH is a
      stronger H-bond donor than that in primary OH, while the O atom in primary OH is
      a stronger H-bond acceptor than that in COOH. The H-bond formed by two COOH is,
      therefore, weaker than that formed by COOH (as donor) and OH (as acceptor), which
      makes nuC=O shift to lower frequency in DMPA than in DMBA.

PMID- 16112605
TI  - Studies on the structure behavior of triphenyldichlorophosphorane in different
      solvents.
AB  - Triphenyldichlorophosporane, which was prepared according to Appel reaction, was
      an efficient reagent for alkyl halide synthesis by virtue of having two
      replaceable groups on "pentavalent" phosphorus. The reaction of
      triphenylphosphine with hexachloroethane was investigated in different solvents
      and 31P NMR traced the processes of these reactions. As results, it was found
      that there was similar high coordinated phosphorus species formed in aromatic
      solvents and in ring ether type solvents, which had large 1J(P-C) (about 140 Hz)
      according to 13C NMR experiments. It is indicated that, for some solvent such as
      benzene or dioxane, solvent molecules might be locked in the high coordinated
      phosphorus compounds, which in turn would affect the triphenyl groups situated at
      the equatorial position.

PMID- 16112606
TI  - Spectral image adaptation and visual experience of DBA/PMMA.
AB  - High resolution S0-->Sn and T1-->Tn electronic absorptions and B-type delayed
      fluorescence of 1,2,7,8-dibenzanthracene in polymethylmethacrylate (PMMA) were
      experimentally observed by flash and laser flash photolysis technique.
      Dibenzanthracene (hereafter DBA) molecules were excited in a two-step process. In
      the first step, an excited singlet is created, which undergoes intersystem
      crossing to triplet state, then T-T absorption creates an excited triplet
      dibenzanthracene molecule, which returns to the first excited singlet level by
      intersystem crossing. The re-created first excited singlet of dibenzanthracene
      decays back to the ground state by emitting B-type of delayed fluorescence, which
      was observed at the same emission band of prompt (normal) fluorescence, and R-, E
      , P-types of delayed fluorescences. For normal fluorescence, S1 state is decaying
      to S0 ground state. For E- and P-type of delayed fluorescences, T1 state is
      decaying to S0 via S1 state, and for B-type of delayed fluorescence, T2 state is
      decaying to S0 via S1 state. The spectrum image showing the absorption/emission
      bands mentioned was also examined by image processing techniques in order to
      improve the visual experience of each band by localizing to a specific region of
      interest (ROI). Experimental results illustrate how the exact location of
      emission/absorption bands was clearly extracted from the spectral image and
      further improvements in the visual detection of absorption/emission bands.

PMID- 16112607
TI  - Electronic, EPR, magnetic and mass spectral studies of mono and homo-binuclear
      Co(II) and Cu(II) complexes with a novel macrocyclic ligand.
AB  - A series of 20-memebered macro-cyclic metal(II) complexes have been synthesized
      by a macro-cyclic ligand, i.e. 1,5,11,15-tetraaza-6,10,16,20-tetraoxo-8,18-dithia
      cyclocosane, it was prepared by the condensation reaction of 1,3-diaminopropane
      with thiodiglycolic acid. The bonding and stereochemistry of the complexes have
      been characterized by elemental analysis, magnetic moment, molar conductance,
      mass, 1H NMR, IR, electronic and EPR spectral studies. The mononuclear complexes
      of the type [ML]X2 have been found to have distorted octahedral geometry and the
      binuclear complexes [M2LX2]X2 were found to possess square planar configuration
      around the central metal ion.

PMID- 16112608
TI  - Synthesis, spectral and thermal studies of Co(II), Ni(II) and Cu(II) complexes 1
      (4,6-dimethyl-pyrimidin-2-ylazo)-naphthalen-2-ol.
AB  - The electronic absorption spectra of 1-(4,6-dimethyl-pyrimidin-2-ylazo)
      naphthalen-2-ol is studied in organic solvents of different polarity as well as
      in buffer solutions of varying pH values at different temperatures and different
      ratios of methanol. The probable structure of the azodye has been assigned on the
      basis of spectral studies (IR and (1)H NMR). The effect of Co(II), Ni(II) and
      Cu(II) ions on the emission spectrum of the free azodye is also assigned. The
      stoichiometry of the metal complexes is determined spectrophotometrically and
      conductometrically. Novel complexes of Co(II), Ni(II) and Cu(II) with the
      pyrimidine azodye have been synthesized and characterized on the basis of
      elemental analyses, molar conductance, magnetic susceptibility measurements, IR,
      electronic as well as ESR spectral studies The thermal decomposition of the metal
      complexes is studied by TGA and DTA techniques. The kinetic parameters like
      activation energy, pre-exponential factor and entropy of activation are
      estimated.

PMID- 16112609
TI  - Zone analysis in biology articles as a basis for information extraction.
AB  - In the field of biomedicine, an overwhelming amount of experimental data has
      become available as a result of the high throughput of research in this domain.
      The amount of results reported has now grown beyond the limits of what can be
      managed by manual means. This makes it increasingly difficult for the researchers
      in this area to keep up with the latest developments. Information extraction (IE)
      in the biological domain aims to provide an effective automatic means to
      dynamically manage the information contained in archived journal articles and
      abstract collections and thus help researchers in their work. However, while
      considerable advances have been made in certain areas of IE, pinpointing and
      organizing factual information (such as experimental results) remains a
      challenge. In this paper we propose tackling this task by incorporating into IE
      information about rhetorical zones, i.e. classification of spans of text in terms
      of argumentation and intellectual attribution. As the first step towards this
      goal, we introduce a scheme for annotating biological texts for rhetorical zones
      and provide a qualitative and quantitative analysis of the data annotated
      according to this scheme. We also discuss our preliminary research on automatic
      zone analysis, and its incorporation into our IE framework.

PMID- 16112610
TI  - Cytomegalovirus-specific CD4 T-cell and glycoprotein B specific antibody response
      in recipients of allogenic stem cell transplantation.
AB  - BACKGROUND: The human cytomegalovirus (HCMV) causes severe complications in
      immunosuppressed patients, resulting in increased morbidity and mortality. The
      immunological components important for the control of HCMV are still not
      completely understood. OBJECTIVE AND STUDY DESIGN: To evaluate the importance of
      cellular and humoral immunity in stem cell transplant (SCT) recipients, we
      analysed levels of HCMV specific IFN-gamma producing CD4+ cells and glycoprotein
      B (gB) specific antibodies in HCMV positive SCT patients with and without
      reactivation episodes after SCT. RESULTS AND CONCLUSION: Patients without HCMV
      reactivation episodes showed a slow but steady increase in both parameters after
      SCT, indicating that initial high levels of gB specific antibodies or HCMV
      specific CD4+ IFN-gamma+ cells are not necessary to prevent reactivation of HCMV.
      In contrast, patients with reactivation episodes showed a steep, significant
      increase in HCMV specific CD4+ IFN-gamma+ counts just prior to HCMV reactivation,
      followed by a decline after the reactivation period. Patients who underwent only
      a single reactivation generated significant higher amounts of CD4+ IFN-gamma+
      cells, than did patients with further reactivation episodes. The course of gB
      specific antibodies for reactivating patients was different, with significantly
      higher average values in the patients with HCMV reactivation. This indicates that
      patients with a HCMV reactivation exhibit a stronger humoral dominated immune
      response.

PMID- 16112611
TI  - Detection of antibodies to hepatitis C virus: false-negative results in an
      automated chemiluminescent microparticle immunoassay (ARCHITECT Anti-HCV)
      compared to a microparticle enzyme immunoassay (AxSYM HCV Version 3.0).
AB  - BACKGROUND: Following an accidental observation of reduced sensitivity for
      detection of antibodies to hepatitis C virus (HCV) with a novel commercially
      available automated chemiluminescent microparticle immunoassay (CMIA, ARCHITECT
      Anti-HCV) compared to a well-established microparticle enzyme immunoassay (MEIA,
      AxSYM HCV Version 3.0), we wanted to explore whether this could be explained by a
      variation in marginal sensitivity, to be expected between highly sensitive assays
      of different formats, or represented a reduced sensitivity of the CMIA to certain
      antibody profiles. OBJECTIVES: To evaluate the ability of the CMIA to detect low
      concentrations of anti-HCV antibodies as defined by various patterns in the
      recombinant immunoblot assay (RIBA) and already detected in the MEIA system.
      STUDY DESIGN: All patient sera tested for anti-HCV reactivity during a period of
      3 years (27,978) were evaluated. A total of 90 sera had a sample/cut-off ratio
      (S/CO) between 1.0 and 1.5 in the MEIA test and were available for further
      testing. Of these, 19 had a probable/possible presence of anti-HCV antibodies
      based on presence of at least two bands of > or = 1+ strength in the RIBA, or
      because the patient was known to be anti-HCV positive. These 19 sera were tested
      with the CMIA. In addition, 16 sera with strong reactivity to various antigen
      combinations in the RIBA were serially diluted until testing negative in both
      microparticle test systems. RESULTS: Seven of the 19 sera (37%) were negative
      (S/CO < 1.0) in the CMIA. At least 3 (16%) of these 19 sera were very likely to
      be true anti-HCV positive sera (from infants with known anti-HCV positive
      mothers). HCV-RNA was not detected in any of the sera tested. Testing of sera
      after serial dilution indicates that the CMIA has a lower sensitivity to c22- and
      c33c-antibodies than the MEIA, possibly also to c100-3-antibodies. CONCLUSION:
      Our findings indicate that ARCHITECT Anti-HCV is less sensitive than AxSYM HCV
      Version 3.0 in detecting antibodies to c22 and c33c in patients who have cleared
      their HCV-infection and have naturally declining levels of antibodies.

PMID- 16112612
TI  - Anti-SARS-CoV IgG response in relation to disease severity of severe acute
      respiratory syndrome.
AB  - BACKGROUND: The association between a robust or depressed antibody response and
      clinical severity of SARS remains unknown. OBJECTIVES: To study seroconversion
      and the magnitude of IgG responses in a SARS cohort with different disease
      severities. STUDY DESIGN AND METHOD: A retrospective analysis of all acute and
      convalescent-phase sera collected from a cohort of laboratory-confirmed SARS
      cases. Anti-SARS-CoV IgG antibody was detected using indirect immunofluorescence
      technique and quantified by two-fold serial dilutions. Characteristics of
      patients who seroconverted "early" (<median interval) were compared to those
      documented to remain sero-negative during the same time interval. Median IgG
      levels in convalescent-phase sera (collected within 30 days) were compared among
      patients with different disease severities. Correlations between IgG levels and
      important laboratory parameters were assessed. RESULTS: A total of 325 laboratory
      confirmed SARS cases were analyzed; of which 301 (92.6%) had anti-SARS-CoV IgG
      detected in their sera at the time of sampling. IgG was first detected on day 4
      of illness; seroconversion occurred at a median of 16 days (range 4-35 days), and
      IgG peak levels were reached in the fourth week. Early seroconversion (<day 16)
      occurred more frequently among patients who required ICU-admission (chi2;
      p=0.011). Higher IgG levels were detected in patients who required supplemental
      oxygen (Mann-Whitney; p=0.002), ICU-admission (p=0.001), had negative pre
      discharge fecal RT-PCR results (p=0.004), and lymphopenia at presentation
      (p=0.028). Peak IgG titres also correlated positively with peak LDH levels
      (Spearman's r=+0.360; p<0.001) among survivors. CONCLUSIONS: Severe SARS is
      associated with a more robust IgG response.

PMID- 16112613
TI  - Natural history of oral papillomavirus infections in spouses: a prospective
      Finnish HPV Family Study.
AB  - BACKGROUND: The natural history of genital human papillomavirus infection is well
      known, but nearly nothing is known about the outcome of oral HPV-infection.
      OBJECTIVES AND STUDY DESIGN: To study natural history of oral HPV in spouses
      during the follow-up 331 women (mean 25.5+/-3.4 years) and 131 men (mean 28.8+/
      5.0 years) were recruited from maternity unit. Scrapings from healthy oral mucosa
      of spouses at baseline, 2, 6, 12 and 24 months and genital samples were taken for
      HPV testing. HPV DNA was detected by nested PCR and confirmed by hybridization
      using a cocktail of 12 high-risk (HR) oligoprobes. RESULTS: The detection rate of
      HR HPVs varied from 15% to 27%. Baseline oral HPV status between the spouses was
      closely related (odds ratio 4.3; 95% confidence interval 1.6-12.0; P=0.006).
      Persistent oral infection in one spouse was a significant risk factor (odds ratio
      10.0; 95% confidence interval 1.5-68.7; P=0.005) for oral HR HPV persistence in
      the other partner. Cumulative incidence of new HR HPV infections was identical in
      both spouses, while men seemed to clear their infection more rapidly. In
      univariate survival analysis, the partner's oral or genital HPV status, oral sex
      habits or age did not predict clearance or acquisition of oral HR HPV.
      CONCLUSION: Natural history of HPV infection in oral mucosa mimics that of
      genital HPV infection. Oral sex had no association to oral HPV infection, but a
      persistent oral HPV infection of the spouse increased the risk of persistent oral
      HPV infection 10-fold in the other spouse.

PMID- 16112614
TI  - Effects of fish oil feeding and fasting on LXRalpha/RXRalpha binding to LXRE in
      the SREBP-1c promoter in mouse liver.
AB  - High-fish oil feeding and fasting down-regulate sterol regulatory element-binding
      protein-1c (SREBP-1c) mRNA level and suppress lipogenesis in mouse liver.
      Previous promoter analysis revealed that liver X receptor alpha
      (LXRalpha)/retinoid X receptor alpha (RXRalpha) complex was required for SREBP-1c
      gene expression in cell culture. In in vitro studies, polyunsaturated fatty acids
      (PUFAs, n-6, n-3) inhibited binding of LXRalpha/RXRalpha heterodimer to LXR
      responsive elements (LXREs) in the SREBP-1c promoter. To examine whether fish oil
      feeding and fasting would also inhibit its binding to LXREs in mouse liver,
      active liver nuclear extracts were prepared by percoll gradient centrifugation,
      and gel mobility shift assay was conducted. Although 1- to 5-day fish oil feeding
      and 2-day fasting decreased SREBP-1c mRNA by 45-68% and 65%, respectively, fish
      oil feeding decreased binding of LXR/RXR heterodimer to LXREs by 0-26%, while 2
      day fasting decreased their binding by 40-56%. Luciferase assay using mutation of
      LXREs in mouse primary hepatocytes revealed that the LXR ligand, T0901317,
      induced increased transcription of SREBP-1c mRNA was mediated by LXREs, but it is
      unknown whether fish oil/eicosapentaenoic acid (EPA)-induced down-regulation of
      SREBP-1c mRNA was mediated by LXREs. These data indicate that high-fish oil
      feeding might decrease SREBP-1c mRNA partly by decreased transcription of SREBP
      1c, but if so, the binding inhibition of LXRalpha to LXREs might not be a major
      cause, while fasting decreased SREBP-1c mRNA, mainly by its binding inhibition of
      LXRalpha to LXREs in the SREBP-1c promoter.

PMID- 16112615
TI  - Speciation in parasites: a population genetics approach.
AB  - Parasite speciation and host-parasite coevolution should be studied at both
      macroevolutionary and microevolutionary levels. Studies on a macroevolutionary
      scale provide an essential framework for understanding the origins of parasite
      lineages and the patterns of diversification. However, because coevolutionary
      interactions can be highly divergent across time and space, it is important to
      quantify and compare the phylogeographic variation in both the host and the
      parasite throughout their geographical range. Furthermore, to evaluate
      demographic parameters that are relevant to population genetics structure, such
      as effective population size and parasite transmission, parasite populations must
      be studied using neutral genetic markers. Previous emphasis on larger-scale
      studies means that the connection between microevolutionary and macroevolutionary
      events is poorly explored. In this article, we focus on the spatial fragmentation
      of parasites and the population genetics processes behind their diversification
      in an effort to bridge the micro- and macro-scales.

PMID- 16112616
TI  - Diminished neo-antigen response to keyhole limpet hemocyanin (KLH) vaccines in
      patients after treatment with chemotherapy or hematopoietic cell transplantation.
AB  - Relapse is the most common cause of treatment failure for advanced cancer, even
      those treated with autologous hematopoietic cell transplantation (HCT). Effective
      tumor-specific immunotherapy may decrease relapse, however, this will fail if the
      immune system is unable to respond. We developed a strategy to test immune
      responses with a single injection of the bona fide neo-antigen KLH. The model was
      first tested in 37 normal volunteers using three KLH vaccines: Intracel KLH,
      Biosyn KLH, and Biosyn KLH + adjuvant. Despite finding the immunogenic epitope
      conserved in both products, intact Intracel KLH induced a better response
      compared to a purified 350/390 kDA subunit of KLH contained in the Biosyn KLH
      product. Addition of a synthetic oil adjuvant (Montanide ISA51) restored the
      response to a single injection of Biosyn KLH. A quantitative readout measured by
      a KLH-specific cellular and humoral response with isotype switching 1 month after
      KLH vaccination was established. To test the integrity of the adaptive immune
      response in cancer patients, we vaccinated 14 patients post-HCT and 19 patients
      with advanced cancer with KLH vaccines that elicited a 100% response rate in
      normal volunteers. In marked contrast to normal subjects, both responses were
      significantly impaired up to 16 months after autologous HCT with an intermediate
      response in advanced cancer patients. KLH vaccines are safe and require only a
      single injection to test neo-antigen responses providing an optimal platform for
      definitive testing of strategies to improve diminished immune recovery after
      chemotherapy or post-HCT.

PMID- 16112617
TI  - Elevated plasma interleukin-18 is a marker of insulin-resistance in type 2
      diabetic and non-diabetic humans.
AB  - Elevated plasma IL-18 is present in several conditions sharing insulin-resistance
      as common trait, but the association with insulin-resistance per se is not
      established. Plasma/serum IL-6, IL-18, TNF-alpha, soluble TNF receptor II
      (sTNFR2), and C-reactive protein (CRP) were measured in 97 patients with type 2
      diabetes (DM) and 84 non-diabetic controls (CON). The association with insulin
      resistance-estimated using the homeostasis model assessment (HOMA-IR)-was
      analyzed using multivariate linear and logistic regression. Compared to CON, DM
      demonstrated higher plasma levels of IL-18 (P = 0.001), IL-6 (P < 0.001), sTNFR2
      (P = 0.005), and CRP (P < 0.001), while TNF-alpha was lower (P = 0.017). Plasma
      IL-18 increased across HOMA-IR quartiles in both DM and CON, both with and
      without adjustment for confounders (all P < 0.05). In contrast, neither IL-6, TNF
      alpha, sTNFR2, nor CRP was associated with HOMA-IR in CON when adjusting for
      confounders. Accordingly, 50% increase of IL-18 corresponded to a marked increase
      of HOMA-IR in both DM and CON (DM: 26%, P = 0.014; CON: 25%, P = 0.003) after
      adjustment for confounders. Our results show that plasma IL-18 was associated
      with HOMA-IR independent of obesity and type 2 diabetes.